PMID- 22623186
TI  - Color changes of autopolymerized silicone or acrylic soft denture reliners: the
      effect of accelerated aging.
AB  - The aim of this in vitro study was to investigate the effect of accelerated aging
      on the color stability of six autopolymerized silicone and acrylic soft reliners.
      Ten specimens for each material were fabricated. Initial color was measured with
      a tri-stimulus colorimeter. One set of five specimens was placed in distilled
      water at 37  degrees C under dark for 15 days, while the remaining were subjected
      to photoaging initially for 1 and then for 6 days. Color changes (DeltaE) then
      calculated. Data were analysed by ANOVA, Tukey and t tests at a = 0.05. All the
      reliners after storage in water showed DeltaE ranged from 2.8 (Mucopren Soft) to
      7.9 (Vertex Soft). After accelerated aging for 1 day, DeltaE ranged from 4.6
      (Vertex Soft) to 12.4 (Eversoft) whereas after 6 days from 1.7 (Ufigel SC) to
      11.8 (Eversoft). All the reliners showed perceptible DeltaE except Ufigel SC in 6
      days aging and clinically unacceptable DeltaE except Sofreliner S and Vertex Soft
      after aging for 1 day. Eversoft showed the highest discoloration after aging. 

PMID- 22623187
TI  - Why might they be giants? Towards an understanding of polar gigantism.
AB  - Beginning with the earliest expeditions to the poles, over 100 years ago,
      scientists have compiled an impressive list of polar taxa whose body sizes are
      unusually large. This phenomenon has become known as 'polar gigantism'. In the
      intervening years, biologists have proposed a multitude of hypotheses to explain
      polar gigantism. These hypotheses run the gamut from invoking release from
      physical and physiological constraints, to systematic changes in developmental
      trajectories, to community-level outcomes of broader ecological and evolutionary
      processes. Here we review polar gigantism and emphasize two main problems. The
      first is to determine the true strength and generality of this pattern: how
      prevalent is polar gigantism across taxonomic units? Despite many published
      descriptions of polar giants, we still have a poor grasp of whether these species
      are unusual outliers or represent more systematic shifts in distributions of body
      size. Indeed, current data indicate that some groups show gigantism at the poles
      whereas others show nanism. The second problem is to identify underlying
      mechanisms or processes that could drive taxa, or even just allow them, to evolve
      especially large body size. The contenders are diverse and no clear winner has
      yet emerged. Distinguishing among the contenders will require better sampling of
      taxa in both temperate and polar waters and sustained efforts by comparative
      physiologists and evolutionary ecologists in a strongly comparative framework.

PMID- 22623188
TI  - Flexural stiffness and composition of the batoid propterygium as predictors of
      punting ability.
AB  - Elasmobranchs (sharks, skates and rays) perform at the extremes of locomotion and
      feeding (i.e. long migrations, high-speed swimming and durophagy). However, very
      little is known about their cartilaginous skeletal structure and composition in
      response to loading regimes. In this study, we investigated a batoid (skate and
      ray) appendicular skeletal element, the propterygium, and its response to forces
      experienced during punting (benthic pelvic fin locomotion). Punting places a
      flexural load on this thin, rod-like element. The goals for our study were to
      determine: (1) the mechanical and compositional properties of the propterygium
      and (2) whether these properties correlate with punting ability. Using five
      batoid species of varying punting ability, we employed a three-point bending test
      and found that propterygium flexural stiffness (33.74-180.16 Nm(2)) was similar
      to values found in bone and could predict punting ability. Variation in flexural
      stiffness resulted from differences in mineral content (24.4-48.9% dry mass) and
      the second moment of area. Propterygia material stiffness (140-2533 MPa)
      approached the lower limit of bone despite having less than one-third of its
      mineral content. This drastically lower mineral content is reflected in the
      radius-to-thickness ratio of the cross-section (mean +/- s.e.m.=5.5 +/- 0.44),
      which is comparatively much higher than bony vertebrates. This indicates that
      elasmobranchs may have evolved skeletal elements that increase buoyancy without
      sacrificing mechanical properties. Our results highlight the functional parallels
      between a cartilaginous and bony skeleton despite dramatic compositional
      differences, and provide insight into how environmental factors may affect
      cartilaginous skeletal development.

PMID- 22623189
TI  - Seasonal variation in metabolic rate, flight activity and body size of Anopheles
      gambiae in the Sahel.
AB  - Malaria in Africa is vectored primarily by the Anopheles gambiae complex.
      Although the mechanisms of population persistence during the dry season are not
      yet known, targeting dry season mosquitoes could provide opportunities for vector
      control. In the Sahel, it appears likely that M-form A. gambiae survive by
      aestivation (entering a dormant state). To assess the role of eco-physiological
      changes associated with dry season survival, we measured body size, flight
      activity and metabolic rate of wild-caught mosquitoes throughout 1 year in a
      Sahelian locality, far from permanent water sources, and at a riparian location
      adjacent to the Niger River. We found significant seasonal variation in body size
      at both the Sahelian and riparian sites, although the magnitude of the variation
      was greater in the Sahel. For flight activity, significant seasonality was only
      observed in the Sahel, with increased flight activity in the wet season when
      compared with that just prior to and throughout the dry season. Whole-organism
      metabolic rate was affected by numerous biotic and abiotic factors, and a
      significant seasonal component was found at both locations. However, assay
      temperature accounted completely for seasonality at the riparian location, while
      significant seasonal variation remained after accounting for all measured
      variables in the Sahel. Interestingly, we did not find that mean metabolic rate
      was lowest during the dry season at either location, contrary to our expectation
      that mosquitoes would conserve energy and increase longevity by reducing
      metabolism during this time. These results indicate that mosquitoes may use
      mechanisms besides reduced metabolic rate to enable survival during the Sahelian
      dry season.

PMID- 22623190
TI  - A nicotinic acetylcholine receptor agonist affects honey bee sucrose
      responsiveness and decreases waggle dancing.
AB  - A nicotinic acetylcholine receptor agonist, imidacloprid, impairs memory
      formation in honey bees and has general effects on foraging. However, little is
      known about how this agonist affects two specific aspects of foraging: sucrose
      responsiveness (SR) and waggle dancing (which recruits nestmates). Using lab and
      field experiments, we tested the effect of sublethal doses of imidacloprid on (1)
      bee SR with the proboscis extension response assay, and (2) free-flying foragers
      visiting and dancing for a sucrose feeder. Bees that ingested imidacloprid (0.21
      or 2.16 ng bee(-1)) had higher sucrose response thresholds 1 h after treatment.
      Foragers that ingested imidacloprid also produced significantly fewer waggle
      dance circuits (10.5- and 4.5-fold fewer for 50% and 30% sucrose solutions,
      respectively) 24 h after treatment as compared with controls. However, there was
      no significant effect of imidacloprid on the sucrose concentrations that foragers
      collected at a feeder 24 h after treatment. Thus, imidacloprid temporarily
      increased the minimum sucrose concentration that foragers would accept (short
      time scale, 1 h after treatment) and reduced waggle dancing (longer time scale,
      24 h after treatment). The effect of time suggests different neurological effects
      of imidacloprid resulting from the parent compound and its metabolites. Waggle
      dancing can significantly increase colony food intake, and thus a sublethal dose
      (0.21 ng bee(-1), 24 p.p.b.) of this commonly used pesticide may impair colony
      fitness.

PMID- 22623191
TI  - A test of the validity of range of motion studies of fossil archosaur elbow
      mobility using repeated-measures analysis and the extant phylogenetic bracket.
AB  - Recent studies have presented range of motion (ROM) data in degrees for dinosaur
      forelimb joints, usually via physical manipulation of one individual. Using these
      data, researchers have inferred limb orientations, postures, gaits, ecological
      functions and even phylogenetic trends within clades. However, important areas of
      concern remain unaddressed; for example, how does ROM at a forelimb joint change
      after soft tissues are lost in archosaurs? And are fossil ROM methodologies
      amenable to reproducibility and statistical analysis? Here, we investigated these
      questions using the extant phylogenetic bracket of dinosaurs. Repeated measures
      of elbow joint ROM from Struthio camelus and Alligator mississippiensis forelimbs
      were statistically analyzed as they were sequentially dissected through five
      levels of tissue removal treatment. Our data indicate that there are no
      statistically significant differences in repeated measures of ROM between
      observers who use the same techniques. Extrinsic soft tissues, such as
      integument, muscles and ligaments were found to impede ROM at the elbow joint.
      Intrinsic soft tissues, such as articular cartilage, may increase ROM. The
      hypothesis that the articular surfaces of the bones within the elbow joints of
      archosaurs provide a general approximation of mobility is supported. Final ROMs
      were less than the initial ROMs in both taxa, which suggests that prior reports
      of elbow joint ROMs in degrees for nonavian dinosaurs may represent conservative
      estimates. We conclude that if observer bias and other variables are controlled
      for, ROM studies of fossil archosaur limbs can obtain useful degree data for
      inferring joint mobility in vivo.

PMID- 22623192
TI  - Mitochondrial function in sparrow pectoralis muscle.
AB  - Flying birds couple a high daily energy turnover with double-digit millimolar
      blood glucose concentrations and insulin resistance. Unlike mammalian muscle,
      flight muscle predominantly relies on lipid oxidation during locomotion at high
      fractions of aerobic capacity, and birds outlive mammals of similar body mass by
      a factor of three or more. Despite these intriguing functional differences, few
      data are available comparing fuel oxidation and free radical production in avian
      and mammalian skeletal muscle mitochondria. Thus we isolated mitochondria from
      English sparrow pectoralis and rat mixed hindlimb muscles. Maximal O(2)
      consumption and net H(2)O(2) release were measured in the presence of several
      oxidative substrate combinations. Additionally, NAD- and FAD-linked electron
      transport chain (ETC) capacity was examined in sonicated mitochondria. Sparrow
      mitochondria oxidized palmitoyl-l-carnitine 1.9-fold faster than rat mitochondria
      and could not oxidize glycerol-3-phosphate, while both species oxidized pyruvate,
      glutamate and malate-aspartate shuttle substrates at similar rates. Net H(2)O(2)
      release was not significantly different between species and was highest when
      glycolytic substrates were oxidized. Sonicated sparrow mitochondria oxidized NADH
      and succinate over 1.8 times faster than rat mitochondria. The high ETC catalytic
      potential relative to matrix substrate dehydrogenases in sparrow mitochondria
      suggests a lower matrix redox potential is necessary to drive a given O(2)
      consumption rate. This may contribute to preferential reliance on lipid
      oxidation, which may result in lower in vivo reactive oxygen species production
      in birds compared with mammals.

PMID- 22623193
TI  - Inducible tolerance to dietary protease inhibitors in Daphnia magna.
AB  - Daphnia has been shown to acquire tolerance to cyanobacterial toxins within an
      animals' lifetime and to transfer this tolerance to the next generation. Here we
      used a strain of the cyanobacterium Microcystis aeruginosa, which contained two
      chymotrypsin inhibitors (BN920 and CP954), the green alga Scenedesmus obliquus as
      reference food and a clone of D. magna to investigate the physiological mechanism
      of acquired tolerance to these cyanobacterial toxins. The intracellular
      concentrations of CP954 and BN920 were 1550 and 120 MUmol l(-1), respectively.
      When food suspensions of the green alga contained >60% M. aeruginosa, growth
      rates of D. magna were reduced. When grown on the green alga, three chymotrypsins
      ranging in mass from 16 to 22 kDa were distinguished in D. magna. Purified BN920
      and CP954 specifically inhibited D. magna chymotrypsins. Feeding with
      encapsulated BN920 resulted in growth depression in D. magna and replacement of
      the chymotrypsins by three chymotrypsins with smaller molecular mass. With just
      20% M. aeruginosa, the same changes in the chymotrypsin pattern as with the pure
      inhibitor were observed. IC(50) values for inhibition of chymotrypsins of D.
      magna growing on the green alga were 5.4 nmol l(-1) (BN920) and 7.4 nmol l(-1)
      (CP954). When D. magna was grown on 20% M. aeruginosa, 2.2-fold higher IC(50)
      values were observed. This indicated that increased tolerance to these dietary
      inhibitors was acquired within an animal's lifetime by remodelling the digestive
      chymotrypsins, which in turn serves as an intra-generational defence against
      these cyanobacterial inhibitors. This mechanism might be relevant for the
      transfer of tolerance to the next generation through maternal effects.

PMID- 22623194
TI  - Feeding in the dark: lateral-line-mediated prey detection in the peacock cichlid
      Aulonocara stuartgranti.
AB  - The cranial lateral line canal system of teleost fishes is morphologically
      diverse and is characterized by four patterns. One of these, widened lateral line
      canals, has evolved convergently in a wide range of teleosts, including the Lake
      Malawi peacock cichlids (Aulonocara), and has been attributed to its role in prey
      detection. The ability to study Aulonocara in the laboratory provides an
      opportunity to test the hypothesis that their reported ability to feed on
      invertebrate prey living in sandy substrates in their natural habitat is the
      result of lateral-line-mediated prey detection. The goal of this study was to
      determine whether Aulonocara stuartgranti could detect hydrodynamic stimuli
      generated by tethered brine shrimp (visualized using digital particle image
      velocimetry) under light and dark conditions, with and without treatment with
      cobalt chloride, which is known to temporarily inactivate the lateral line
      system. Fish were presented with six pairs of tethered live and dead adult brine
      shrimp and feeding behavior was recorded with HD digital video. Results
      demonstrate that A. stuartgranti: (1) uses the same swimming/feeding strategy as
      they do in the field; (2) detects and consumes invertebrate prey in the dark
      using its lateral line system; (3) alters prey detection behavior when feeding on
      the same prey under light and dark conditions, suggesting the involvement of
      multiple sensory modalities; and (4) after treatment with cobalt chloride,
      exhibits a reduction in their ability to detect hydrodynamic stimuli produced by
      prey, especially in the dark, thus demonstrating the role of the lateral line
      system in prey detection.

PMID- 22623195
TI  - Localized fluidization burrowing mechanics of Ensis directus.
AB  - Muscle measurements of Ensis directus, the Atlantic razor clam, indicate that the
      organism only has sufficient strength to burrow a few centimeters into the soil,
      yet razor clams burrow to over 70 cm. In this paper, we show that the animal uses
      the motions of its valves to locally fluidize the surrounding soil and reduce
      burrowing drag. Substrate deformations were measured using particle image
      velocimetry (PIV) in a novel visualization system that enabled us to see through
      the soil and watch E. directus burrow in situ. PIV data, supported by soil and
      fluid mechanics theory, show that contraction of the valves of E. directus
      locally fluidizes the surrounding soil. Particle and fluid mixtures can be
      modeled as a Newtonian fluid with an effective viscosity based on the local void
      fraction. Using these models, we demonstrate that E. directus is strong enough to
      reach full burrow depth in fluidized soil, but not in static soil. Furthermore,
      we show that the method of localized fluidization reduces the amount of energy
      required to reach burrow depth by an order of magnitude compared with penetrating
      static soil, and leads to a burrowing energy that scales linearly with depth
      rather than with depth squared.

PMID- 22623196
TI  - Skeletal muscles of hibernating brown bears are unusually resistant to effects of
      denervation.
AB  - Hibernating bears retain most of their skeletal muscle strength despite
      drastically reduced weight-bearing activity. Regular neural activation of muscles
      is a potential mechanism by which muscle atrophy could be limited. However, both
      mechanical loading and neural activity are usually necessary to maintain muscle
      size. An alternative mechanism is that the signaling pathways related to the
      regulation of muscle size could be altered so that neither mechanical nor neural
      inputs are needed for retaining strength. More specifically, we hypothesized that
      muscles in hibernating bears are resistant to a severe reduction in neural
      activation. To test this hypothesis, we unilaterally transected the common
      peroneal nerve, which innervates ankle flexor muscles, in hibernating and summer
      active brown bears (Ursus arctos). In hibernating bears, the long digital
      extensor (LDE) and cranial tibial (CT) musculotendon masses on the denervated
      side decreased after 11 weeks post-surgery by 18 +/- 11 and 25 +/- 10%,
      respectively, compared with those in the intact side. In contrast, decreases in
      musculotendon masses of summer-active bears after denervation were 61 +/- 4 and
      58 +/- 5% in the LDE and CT, respectively, and significantly different from those
      of hibernating bears. The decrease due to denervation in summer-active bears was
      comparable to that occurring in other mammals. Whole-muscle cross-sectional areas
      (CSAs) measured from ultrasound images and myofiber CSAs measured from biopsies
      decreased similarly to musculotendon mass. Thus, hibernating bears alter skeletal
      muscle catabolic pathways regulated by neural activity, and exploration of these
      pathways may offer potential solutions for disuse atrophy of muscles.

PMID- 22623197
TI  - An unusual myosuppressin from the blood-feeding bug Rhodnius prolixus.
AB  - The myosuppressin (MS) gene was cloned from a central nervous system (CNS) cDNA
      library of the hematophagous insect Rhodnius prolixus and is predicted to contain
      two introns and three exons. The mRNA transcribed from the myosuppressin gene
      encodes an 88 amino acid prepropeptide, which results in a mature decapeptide
      after post-translational modification. When compared with the myosuppressins
      isolated from other insects, the R. prolixus myosuppressin has a unique amino
      acid sequence (pQDIDHVFMRFamide), with isoleucine (I) in position 3 and
      methionine (M) in position 8. Reverse transcriptase (RT)-PCR shows that Rhopr-MS
      is expressed in the CNS and posterior midgut in R. prolixus and
      immunohistochemistry suggests that an RFamide-like peptide is present in
      endocrine-like cells in the midgut. Physiological assays using Rhopr-MS indicate
      that, despite the unusual M at position 8, it still retains myoinhibitory
      activity, inhibiting the frequency and reducing the amplitude of contractions in
      the anterior midgut and hindgut, and decreasing heart rate.

PMID- 22623198
TI  - Perch diameter and branching patterns have interactive effects on the locomotion
      and path choice of anole lizards.
AB  - Natural branches vary conspicuously in their diameter, density and orientation,
      but how these latter two factors affect animal locomotion is poorly understood.
      Thus, for three species of arboreal anole lizards found on different size
      branches and with different limb lengths, we tested sprinting performance on
      cylinders with five diameters (5-100 mm) and five patterns of pegs, which
      simulated different branch orientations and spacing. We also tested whether the
      lizards preferred surfaces that enhanced their performance. The overall responses
      to different surfaces were similar among the three species, although the
      magnitude of the effects differed. All species were faster on cylinders with
      larger diameter and no pegs along the top. The short-limbed species was the
      slowest on all surfaces. Much of the variation in performance resulted from
      variable amounts of pausing among different surfaces and species. Lizards
      preferred to run along the top of cylinders, but pegs along the top of the narrow
      cylinders interfered with this. Pegs on top of the 100-mm diameter cylinder,
      however, had little effect on speed as the lizards ran quite a straight path
      alongside pegs without bumping into them. All three species usually chose
      surfaces with greater diameters and fewer pegs, but very large diameters with
      pegs were preferred to much smaller diameter cylinders without pegs. Our results
      suggest that preferring larger diameters in natural vegetation has a direct
      benefit for speed and an added benefit of allowing detouring around branches with
      little adverse effect on speed.

PMID- 22623199
TI  - Targeting a neuropeptide to discrete regions of the motor arborizations of a
      single neuron.
AB  - The heart excitor (HE) motor neuron in the leech Hirudo releases acetylcholine
      (ACh) and a peptide, FMRFamide, to regulate the contractile activity of the heart
      tube and associated side vessels. Consistent with Dale's principle, it was
      assumed that both neurotransmitters were localized to all presynaptic
      varicosities. However, we found discrete peptide-positive and peptide-negative
      varicosities associated with particular sites of innervation on the heart tube.
      We produced dual-labeled HE neurons by pressure injecting Neurobiotin into single
      HE cell bodies and applied anti-FMRFamide antibodies on the same preparations.
      Consistent with initial expectations, peptide-labeled varicosities were numerous
      and widely distributed along the heart tube and at one of the three side vessels,
      the latero-abdominal vessel. Nevertheless, some Neurobiotin-labeled varicosities
      along the heart tube lacked peptide label entirely. Moreover, there were dense
      and distinct peptide-negative innervations at the valve junctions of the latero
      dorsal and latero-lateral vessels at each segment. Nevertheless, the peptide
      label was found in HE axons and varicosities that projected distally along the
      side vessels. Therefore, the more proximal peptide-negative clusters cannot
      simply be the result of restricted transport or deficient staining of peptide.
      Rather, we infer that FMRFamide is transported to (or selectively excluded from)
      discrete locations and that ACh is present in varicosities that lacked peptide.
      Such targeting of neurotransmitters could be described using a discrete targeting
      model of synaptic transmission. Compared with Dale's principle, this model may
      provide a more complete perspective of chemical communication than previously
      understood.

PMID- 22623200
TI  - Birds achieve high robustness in uneven terrain through active control of landing
      conditions.
AB  - We understand little about how animals adjust locomotor behaviour to negotiate
      uneven terrain. The mechanical demands and constraints of such behaviours likely
      differ from uniform terrain locomotion. Here we investigated how common pheasants
      negotiate visible obstacles with heights from 10 to 50% of leg length. Our goal
      was to determine the neuro-mechanical strategies used to achieve robust
      stability, and address whether strategies vary with obstacle height. We found
      that control of landing conditions was crucial for minimising fluctuations in
      stance leg loading and work in uneven terrain. Variation in touchdown leg angle
      (theta(TD)) was correlated with the orientation of ground force during stance,
      and the angle between the leg and body velocity vector at touchdown (beta(TD))
      was correlated with net limb work. Pheasants actively targeted obstacles to
      control body velocity and leg posture at touchdown to achieve nearly steady
      dynamics on the obstacle step. In the approach step to an obstacle, the birds
      produced net positive limb work to launch themselves upward. On the obstacle,
      body dynamics were similar to uniform terrain. Pheasants also increased swing leg
      retraction velocity during obstacle negotiation, which we suggest is an active
      strategy to minimise fluctuations in peak force and leg posture in uneven
      terrain. Thus, pheasants appear to achieve robustly stable locomotion through a
      combination of path planning using visual feedback and active adjustment of leg
      swing dynamics to control landing conditions. We suggest that strategies for
      robust stability are context specific, depending on the quality of sensory
      feedback available, especially visual input.

PMID- 22623201
TI  - High e-vector acuity in the polarisation vision system of the fiddler crab Uca
      vomeris.
AB  - Polarisation vision is used by a variety of species in many important tasks,
      including navigation and orientation (e.g. desert ant), communication and
      signalling (e.g. stomatopod crustaceans), and as a possible substitute for colour
      vision (e.g. cephalopod molluscs). Fiddler crabs are thought to possess the
      anatomical structures necessary to detect polarised light, and occupy
      environments rich in polarisation cues. Yet little is known about the
      capabilities of their polarisation sense. A modified polarisation-only liquid
      crystal display and a spherical rotating treadmill were combined to test the
      responses of fiddler crabs to moving polarisation stimuli. The species Uca
      vomeris was found to be highly sensitive to polarised light and detected stimuli
      differing in e-vector angle by as little as 3.2 deg. This represents the most
      acute behavioural sensitivity to polarised light yet measured for a crustacean.
      The occurrence of null points in their discrimination curve indicates that this
      species employs an orthogonal (horizontal/vertical) receptor array for the
      detection of polarised light.

PMID- 22623202
TI  - New insights into force depression in skeletal muscle.
AB  - Force depression observed following active shortening is not well understood.
      Previous research suggested that force depression might be associated with a
      stress-induced inhibition of cross-bridges in the newly formed overlap zone
      following shortening. Our aim was to investigate this theory in skinned fibres
      and determine whether there was an inhibition of the attachment of cross-bridges
      or a decrease in the force produced per cross-bridge. The stress-induced
      inhibition of cross-bridge theory gives testable predictions, including: (1)
      skinned fibres should show proportional force and stiffness depression, (2) force
      after shortening should not be lower than force before shortening, (3) stiffness
      following shortening should not be lower than stiffness before shortening and (4)
      force depression should decrease when the stress during shortening is decreased.
      In agreement with these predictions, force and stiffness depression were
      approximately proportional, and force depression decreased with decreasing stress
      during shortening. However, in contrast to the predictions of the stress-induced
      inhibition of cross-bridge theory, force after shortening from sarcomere lengths
      of 2.8 and 3.0 MUm to a sarcomere length of 2.4 MUm was smaller than force before
      shortening, and this was not accompanied by a corresponding decrease in
      stiffness. We conclude that the stress-induced inhibition of cross-bridge theory,
      as proposed previously, cannot be the only mechanism for force depression, but
      that there is an additional, stress-induced inhibition of cross-bridges in the
      old overlap zone. Furthermore, both mechanisms, inhibition of cross-bridge
      attachment and reduction of force produced per cross-bridge, contribute to force
      depression. Inhibition and/or reduction of force depend(s) on the amount of
      stress imposed on actin during the shortening phase.

PMID- 22623203
TI  - Hibernation energetics of free-ranging little brown bats.
AB  - Hibernation physiology and energy expenditure have been relatively well studied
      in large captive hibernators, especially rodents, but data from smaller, free
      ranging hibernators are sparse. We examined variation in the hibernation patterns
      of free-ranging little brown bats (Myotis lucifugus) using temperature-sensitive
      radio-transmitters. First, we aimed to test the hypothesis that age, sex and body
      condition affect expression of torpor and energy expenditure during hibernation.
      Second, we examined skin temperature to assess whether qualitative differences in
      the thermal properties of the hibernacula of bats, compared with the burrows of
      hibernating rodents, might lead to different patterns of torpor and arousal for
      bats. We also evaluated the impact of carrying transmitters on body condition to
      help determine the potential impact of telemetry studies. We observed large
      variation in the duration of torpor bouts within and between individuals but
      detected no effect of age, sex or body condition on torpor expression or
      estimates of energy expenditure. We observed the use of shallow torpor in the
      midst of periodic arousals, which may represent a unique adaptation of bats for
      conservation of energy during the most costly phase of hibernation. There was no
      difference in the body condition of hibernating bats outfitted with transmitters
      compared with that of control bats captured from the same hibernaculum at the
      same time. This study provides new information on the energetics of hibernation
      in an under-represented taxon and baseline data important for understanding how
      white-nose syndrome, a new disease devastating populations of hibernating bats in
      North America, may alter the expression of hibernation in affected bats.

PMID- 22623204
TI  - Short-term anoxic conditioning hormesis boosts antioxidant defenses, lowers
      oxidative damage following irradiation and enhances male sexual performance in
      the Caribbean fruit fly, Anastrepha suspensa.
AB  - Most organisms are repeatedly exposed to oxidative stress from multiple sources
      throughout their lifetimes, potentially affecting all aspects of organismal
      performance. Here we test whether exposure to a conditioning bout of anoxia early
      in adulthood induces a hormetic response that confers resistance to oxidative
      stress and enhances male sexual performance later in life in the Caribbean fruit
      fly, Anastrepha suspensa. Anoxic conditioning of adults prior to emergence led to
      an increase in antioxidant capacity driven by mitochondrial superoxide dismutase
      and glutathione peroxidase. When exposed to gamma irradiation, a strong oxidative
      stressor, males that received anoxic conditioning had lower lipid and protein
      oxidative damage at sexual maturity. Anoxia conditioning led to greater male
      sexual competitiveness compared with unconditioned males when both were
      irradiated, although there was no effect of anoxia conditioning on mating
      competitiveness in unirradiated males. Anoxia also led to higher adult emergence
      rates and greater flight ability in irradiation-stressed flies while preserving
      sterility. Thus, hormetic treatments that increased antioxidant enzyme activity
      also improved male performance after irradiation, suggesting that antioxidant
      enzymes play an important role in mediating the relationship between oxidative
      stress and sexual selection. Furthermore, our work has important applied
      implications for the sterile insect technique (SIT), an environmentally friendly
      method of insect pest control where males are sterilized by irradiation and
      deployed in the field to disrupt pest populations via mating. We suggest that
      hormetic treatments specifically designed to enhance antioxidant activity may
      produce more sexually competitive sterile males, thus improving the efficacy and
      economy of SIT programs.

PMID- 22623205
TI  - Polysulfone functionalized with phosphonated poly(pentafluorostyrene) grafts for
      potential fuel cell applications.
AB  - A multi-step synthetic strategy to polysulfone (PSU) grafted with phosphonated
      poly(pentafluorostyrene) (PFS) is developed. It involves controlled radical
      polymerization resulting in alkyne-end functional PFS. The next step is the
      modification of PSU with a number of azide side groups. The grafting of PFS onto
      PSU backbone is performed via the "click"-chemistry approach. In a final step,
      the PFS-grafts are subjected to the post phosphonation. The copolymers are
      evaluated as membranes for potential fuel cell applications through thermal
      analyses, water uptake, and conductivity measurements. The proposed synthetic
      route opens the possibility to tune copolymers' hydrophilic-hydrophobic balance
      to obtain membranes with an optimal balance between proton conductivity and
      mechanical properties.

PMID- 22623206
TI  - Robotic gait training is not superior to conventional treadmill training in
      parkinson disease: a single-blind randomized controlled trial.
AB  - BACKGROUND: The use of robots for gait training in Parkinson disease (PD) is
      growing, but no evidence points to an advantage over the standard treadmill.
      METHODS: In this randomized, single-blind controlled trial, participants aged <75
      years with early-stage PD (Hoehn-Yahr <3) were randomly allocated to 2 groups:
      either 30 minutes of gait training on a treadmill or in the Lokomat for 3 d/wk
      for 4 weeks. Patients were evaluated by a physical therapist blinded to
      allocation before and at the end of treatment and then at the 3- and 6-month
      follow-up. The primary outcome measure was the 6-minute walk test. RESULTS: Of
      334 screened patients, the authors randomly allocated 30 to receive gait training
      with treadmill or the Lokomat. At baseline, the 2 groups did not differ. At the 6
      month follow-up, both groups had improved significantly in the primary outcome
      measure (treadmill: mean = 490.95 m, 95% confidence interval [CI] = 448.56
      533.34, P = .0006; Lokomat: 458.6 m, 95% CI = 417.23-499.96, P = .01), but no
      significant differences were found between the 2 groups (P = .53). DISCUSSION:
      Robotic gait training with the Lokomat is not superior to treadmill training in
      improving gait performance in patients with PD. Both approaches are safe, with
      results maintained for up to 6 months.

PMID- 22623207
TI  - Motor and cognitive impairments in Parkinson disease: relationships with specific
      balance and mobility tasks.
AB  - BACKGROUND: Balance and mobility problems are common for people with Parkinson
      disease (PD). OBJECTIVE: To determine the relationships of motor and cognitive
      impairments with specific balance and mobility task performance. METHODS: A total
      of 82 community-dwelling people with idiopathic PD were tested "on" medication.
      Impairments measured included leg extensor and hip abductor muscle power,
      freezing of gait, dyskinesia, and executive function. Balance and mobility were
      classified into tasks requiring anticipatory control with a change in base of
      support, anticipatory control without a change in support, and reactive
      adjustments in response to external perturbations. Associations between
      impairments and tasks were examined using univariable and multivariable linear
      regression models. RESULTS: Univariable models revealed that muscle power was
      significantly related to balance and mobility, explaining 7% to 33% of the
      variability in task performance. Freezing of gait, dyskinesia, and executive
      function were not consistently related to task performance. Multivariable models
      that included all impairments plus disease severity, age, gender, and height
      explained 5% to 43% of the variability in balance and mobility tasks. Leg muscle
      power was the only impairment with a consistent association with performance of
      tasks involving anticipatory control with a change in base of support (beta = 0.2
      to 0.5), but the association of each muscle group was specific to individual
      tasks. CONCLUSION: Information gained from this study about the relationships
      between impairments and specific balance and mobility tasks may be able to guide
      the development of interventional strategies for people with PD.

PMID- 22623208
TI  - Modeling and simulation approaches to evaluate pharmacokinetic sampling
      contamination from central venous catheters in pediatric pharmacokinetic studies
      of actinomycin-D: a report from the children's oncology group.
AB  - BACKGROUND: The binding of drugs to catheters can be a source variation in dosing
      chemotherapeutics. Drug contamination from the dosing central venous line (CVL)
      can impact the reporting of pharmacokinetic (PK) results and analysis. Peripheral
      venipuncture avoids binding complications from the CVL but dissuades patients
      from enrolling. Our group has developed a catheter clearing procedure to minimize
      the extent of contamination so that dosing and sampling from the CVL can ensue,
      promoting patient willingness to participate in phase I pediatric oncology
      trials. OBJECTIVES: To develop a population pharmacokinetic model of actinomycin
      D (AMD) in children with cancer incorporating expressions for drug contamination
      from PK samples obtained via indwelling CVLs and to evaluate the efficiency of a
      catheter clearing procedure in removing contamination as well as the impact of
      contamination on PK results. METHODS: A dataset of 199 AMD plasma concentration
      measurements from 36 patients (age 1.6-20.3 years) was analyzed using nonlinear
      mixed-effects modeling. Quantitative modeling approaches, including baseline
      contamination model, covariate model, and catheter clearance model, were
      evaluated to describe catheter contamination. Monte Carlo simulations mimicking a
      prospective study in children with cancer were performed to assess the
      performance of the final model and impact of catheter contamination on PK
      reporting. RESULTS: The PK of AMD was best described by a linear 3-compartment
      model with first-order elimination. A baseline contamination model including a
      contamination factor proportional to the model-predicted concentration for
      samples obtained from central catheters was chosen as the most parsimonious and
      accurate among competing models. The final model parameters were allometrically
      scaled to a 70 kg person. The estimated mean parameter values were 11 L/h, 5.79,
      24.2, 490 L, 17.7, and 42.8 L/h for total clearance, central volume of
      distribution, peripheral volume 1, peripheral volume 2, inter-compartmental
      clearance 1, and inter-compartmental clearance 2, respectively. The proportional
      contamination factor was 19.3 % immediately post-drug administration and
      decreased at a first-order rate of 0.0932 h(-1). Simulations precisely re
      estimated kinetic parameters with catheter contamination adjustment. Large
      uncertainty and poor estimation were observed when contamination was ignored.
      CONCLUSIONS: Drug contamination from sampling catheter can impact AMD PK results
      and should be accounted for in the analysis. We provide a framework for
      evaluating catheter contamination and guidance on adjustment in the PK model.

PMID- 22623209
TI  - AZ64 inhibits TrkB and enhances the efficacy of chemotherapy and local radiation
      in neuroblastoma xenografts.
AB  - Neuroblastoma is a common pediatric tumor characterized by clinical
      heterogeneity. Because it is derived from sympathetic neuroblasts, the NTRK
      family of neurotrophin receptors plays an integral role in neuroblastoma cell
      survival, growth, and differentiation. Indeed, high expression of NTRK1 is
      associated with favorable clinical features and outcome, whereas expression of
      NTRK2 and its ligand, brain-derived neurotrophic factor (BDNF), are associated
      with unfavorable features and outcome. AZ64 (Astra Zeneca) is a potent and
      selective inhibitor of the NTRK tyrosine kinases that blocks phosphorylation at
      nanomolar concentrations. To determine the preclinical activity of AZ64, we
      performed intervention trials in a xenograft model with NTRK2-overexpressing
      neuroblastomas. AZ64 alone significantly inhibited tumor growth compared to
      vehicle-treated animals (p = 0.0006 for tumor size). Furthermore, the combination
      of AZ64 with conventional chemotherapeutic agents, irinotecan and temozolomide
      (irino-temo), showed significantly enhanced anti-tumor efficacy compared to irino
      temo alone [(p < 0.0001 for tumor size, p < 0.0005 for event-free survival
      (EFS)]. We also assessed the combination of AZ64 and local radiation therapy (RT)
      on a neuroblastoma hindlimb xenograft model, and the efficacy of local RT was
      significantly increased when animals were treated simultaneously with AZ64 (p <
      0.0001 for tumor size, p = 0.0006 for EFS). We conclude that AZ64 can inhibit
      growth of NTRK-expressing neuroblastomas both in vitro and in vivo. More
      importantly, it can significantly enhance the efficacy of conventional
      chemotherapy as well as local RT, presumably by inhibition of the NTRK2/BDNF
      autocrine survival pathway.

PMID- 22623210
TI  - A phase I study of sunitinib combined with modified FOLFOX6 in patients with
      advanced solid tumors.
AB  - PURPOSE: This phase I study assessed the safety, tolerability, maximum tolerated
      dose (MTD), pharmacokinetics, and preliminary antitumor effects of sunitinib
      combined with modified FOLFOX6 (mFOLFOX6). METHODS: Patients with advanced solid
      malignancies received mFOLFOX6 in 2-week cycles with escalating sunitinib doses
      (25, 37.5, and 50 mg/day) on three schedules: 2 weeks on, 2 weeks off (2/2); 4
      weeks on, 2 weeks off (4/2); or continuous daily dosing (CDD). Patients received
      up to 8 treatment cycles (Schedule 2/2 and CDD schedule) or 6 cycles (Schedule
      4/2). An expansion cohort enrolled patients with metastatic colorectal cancer at
      the Schedule 2/2 MTD. RESULTS: Overall, 53 patients were enrolled, with 43
      evaluable for dose-limiting toxicity (DLT). On Schedule 2/2 (n = 18), DLTs
      occurred in three patients at 50 mg/day (grade 4 neutropenia [n = 1]; grades 3
      and 4 thrombocytopenia [n = 2]) and two patients achieved partial responses
      (PRs). On Schedule 4/2 (n = 13), 37.5 mg/day exceeded the MTD with two DLTs
      (febrile neutropenia and grade 4 hypokalemia, respectively). On the CDD schedule
      (n = 12), the MTD was 25 mg/day; one DLT (grade 3 stomatitis) was reported and
      two patients achieved PRs. The most common adverse events were neutropenia,
      fatigue, and thrombocytopenia. No clinically significant drug-drug interactions
      were apparent between sunitinib, its metabolite SU12662, and mFOLFOX6.
      CONCLUSIONS: Sunitinib combined with mFOLFOX6 had acceptable tolerability. The
      MTDs were sunitinib 50 mg/day on Schedule 2/2 and 25 mg/day on the CDD schedule.
      A MTD for Schedule 4/2 was not established.

PMID- 22623211
TI  - Concurrent use of proton pump inhibitors or H2 blockers did not adversely affect
      nilotinib efficacy in patients with chronic myeloid leukemia.
AB  - PURPOSE: The impact of proton pump inhibitors (PPIs) and histamine H2 receptor
      antagonists (H2 blockers) on the efficacy of nilotinib was evaluated. METHODS:
      Retrospective analyses were performed in patients with newly diagnosed
      Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase
      (CML-CP; N = 492) and in patients with imatinib-resistant or imatinib-intolerant
      Ph+ CML-CP (N = 256) treated with nilotinib. RESULTS: In the newly diagnosed
      population, 87 (17.7 %) and 49 (10.0 %) patients received PPIs and H2 blockers,
      respectively. Major molecular response at 12 months was achieved by 59 (49.6 %)
      patients who received at least one PPI or H2 blocker (n = 119) and 153 (41.0 %)
      patients who did not receive any comedication (n = 373; P = 0.13). PPIs and H2
      blockers were used by 77 (30.1 %) and 17 (6.6 %) patients with imatinib-resistant
      or imatinib-intolerant CML-CP, respectively. Major cytogenetic response by 12
      months was achieved by 55 (64.0 %) patients who received at least one PPI or H2
      blocker (n = 86) versus 98 (57.6 %) patients who did not receive any comedication
      (n = 170; P = 0.40); 39 (45.3 %) versus 65 (38.2 %), respectively, achieved
      complete cytogenetic response by 12 months (P = 0.34). Similar findings were
      observed in patients who received comedication for >50 % of the time on nilotinib
      therapy. Nilotinib steady-state trough concentration was not affected by the
      presence of PPIs or H2 blockers. CONCLUSIONS: Concurrent use of PPIs or H2
      blockers did not affect the pharmacokinetics and efficacy of nilotinib in
      patients with Ph+ CML-CP.

PMID- 22623212
TI  - Genetic polymorphisms of CYP2D6 increase the risk for recurrence of breast cancer
      in patients receiving tamoxifen as an adjuvant therapy.
AB  - PURPOSE: Tamoxifen is used in the treatment of breast cancer to prevent
      recurrences. It is converted to its active metabolite endoxifen by CYP2D6 enzyme.
      This study was conducted to evaluate the influence of CYP2D6 genetic
      polymorphisms on the recurrence of breast cancer in patients receiving treatment
      with tamoxifen as an adjuvant hormonal therapy. METHODS: Breast cancer patients
      (n = 141) on adjuvant tamoxifen and not on any concomitant CYP2D6 inhibitors were
      recruited for the study. Patient characteristics and treatment history were
      obtained. Five milliliters of venous blood was collected for genotyping CYP2D6
      alleles *1, *2, *4, *5 and *10. CYP2D6 activity score was calculated to determine
      the phenotype based on genotype. The activity scores were compared between
      patients with recurrence and patients with no recurrence of breast cancer.
      RESULTS: Of the 141 patients recruited for the study, genotyping was done for 132
      of them. CYP2D6 activity score <=0.5 is associated with a statistically
      significant increased risk of recurrence (OR-12.37; 95 % CI-3.23, 47.33; p <
      0.001) and shorter recurrence free survival (52.68 +/- 10.58 months (mean +/-
      SEM); p < 0.001) as was shown in Kaplan-Meir survival estimates, when compared to
      activity score >=1. The hazard ratio for activity score <=0.5 is 7.29 (p < 0.001)
      when compared to activity score >=1. Analysis of known estrogen receptor positive
      patients also showed statistically significant increased risk of recurrence and
      shorter recurrence free survival in patients with CYP2D6 activity score <=0.5.
      The Cox proportional hazard ratio was found to be 7.15 (p = 0.006) for activity
      score <=0.5. CONCLUSION: Reduced CYP2D6 activity is associated with poor
      treatment outcomes, in terms of increased risk of recurrence and shorter
      recurrence free survival, in breast cancer patients on adjuvant tamoxifen
      therapy.

PMID- 22623213
TI  - Structural origin: water deactivates metal oxides to CO oxidation and promotes
      low-temperature CO oxidation with metals.

PMID- 22623214
TI  - Chitosan oligosaccharides suppress production of nitric oxide in
      lipopolysaccharide-induced N9 murine microglial cells in vitro.
AB  - Chitosan oligosaccharides (COS) have been reported to exert many biological
      activities, such as antioxidant, antitumor and anti-inflammatory effects. In the
      present study, we examined the effect of COS on nitric oxide (NO) production in
      LPS induced N9 microglial cells. Pretreatment with COS (50~200 MUg/ml) could
      markedly inhibit NO production by suppressing inducible nitric oxide synthase
      (iNOS) expression in activated microglial cells. Signal transduction studies
      showed that COS remarkably inhibited LPS-induced phosphorylation of p38 MAPK and
      ERK1/2. COS pretreatment could also inhibit the activation of both nuclear factor
      kappaB (NF-kappaB) and activator protein-1 (AP-1). In conclusion, our results
      suggest that COS could suppress the production of NO in LPS-induced N9 microglial
      cells, mediated by p38 MAPK and ERK1/2 pathways.

PMID- 22623215
TI  - Proteome reference map of Drosophila melanogaster head.
AB  - Drosophila melanogaster has been used as a genetic model organism to understand
      the fundamental molecular mechanisms in human biology including memory formation
      that has been reported involving protein synthesis and/or post-translational
      modification. In this study, we employed a proteomic platform based on
      fluorescent 2DE and MALDI-TOF MS to build a standard D. melanogaster head
      proteome map for proteome-proteome comparison. In order to facilitate the
      comparison, an interactive database has been constructed for systematically
      integrating and analyzing the proteomes from different conditions and further
      implicated to study human diseases related to D. melanogaster model. In summary,
      the fundamental head proteomic database and bioinformatic analysis will be useful
      for further elucidating the biological mechanisms such as memory formation and
      neurodegenerative diseases.

PMID- 22623216
TI  - Treatment and survival of osseous renal cell carcinoma metastases.
AB  - BACKGROUND: Renal cell carcinoma is the seventh leading cause of cancer deaths.
      Studies have shown patients with solitary osseous metastases have a better
      prognosis; however, methods of resection are not well defined. The purpose of
      this study was to review factors associated with survival and assess the impact
      of wide versus intralesional management on function and disease-specific outcomes
      in patients with renal cell carcinoma metastases. METHODS: Sixty-nine patients
      with 86 osseous renal cell metastases were reviewed. Potential factors associated
      with survival were evaluated with Kaplan-Meier curves. ANOVA was performed to
      compare means between groups. RESULTS: One year survival for the group was 77%
      and 32.5% at 5 years. The absence of metastatic disease at presentation,
      nephrectomy, and pre-operative status were associated with improved survival.
      There was a lower rate of local recurrence with wide resection (5%) versus
      intralesional procedures (27%). CONCLUSIONS: Improved pre-operative status,
      nephrectomy, and metachronous lesions had better overall survival. Wide resection
      results in decreased local recurrence and revision surgeries. However, it did not
      reliably predict improved survival. Our recommendation is for individual
      evaluation of each patient with osseous renal cell carcinoma metastases. Wide
      excision may be used for resectable lesions to prevent local progression and
      subsequent surgeries.

PMID- 22623217
TI  - When emotional valence modulates audiovisual integration.
AB  - We constantly integrate the information that is available to our various senses.
      The extent to which the mechanisms of multisensory integration are subject to the
      influences of attention, emotion, and/or motivation is currently unknown. The
      "ventriloquist effect" is widely assumed to be an automatic crossmodal
      phenomenon, shifting the perceived location of an auditory stimulus toward a
      concurrently presented visual stimulus. In the present study, we examined whether
      audiovisual binding, as indicated by the magnitude of the ventriloquist effect,
      is influenced by threatening auditory stimuli presented prior to the
      ventriloquist experiment. Syllables spoken in a fearful voice were presented from
      one of eight loudspeakers, while syllables spoken in a neutral voice were
      presented from the other seven locations. Subsequently, participants had to
      localize pure tones while trying to ignore concurrent visual stimuli (both the
      auditory and the visual stimuli here were emotionally neutral). A reliable
      ventriloquist effect was observed. The emotional stimulus manipulation resulted
      in a reduction of the magnitude of the subsequently measured ventriloquist effect
      in both hemifields, as compared to a control group exposed to a similar attention
      capturing, but nonemotional, manipulation. These results suggest that the
      emotional system is capable of influencing multisensory binding processes that
      have heretofore been considered automatic.

PMID- 22623218
TI  - Assessment of psoriatic nail disease activity by rheumatologists: comment on the
      article by Lubrano et al.

PMID- 22623219
TI  - Skeletal muscle mass is associated with bone geometry and microstructure and
      serum insulin-like growth factor binding protein-2 levels in adult women and men.
AB  - Skeletal muscle and bone form highly-integrated systems that undergo significant
      age-related changes, but the relationships between muscle mass and trabecular
      versus cortical bone or trabecular microarchitecture have not been systematically
      investigated. Thus, we examined the association between appendicular skeletal
      muscle mass (ASM) relative to height squared (relative ASM) and bone parameters
      at several sites assessed by conventional as well as high-resolution peripheral
      QCT in a cohort of 272 women and 317 men aged 20 to 97 years. In women, relative
      ASM was associated with cortical thickness (CtTh) at the femoral neck, lumbar
      spine, radius, and tibia (age-and physical activity adjusted r = 0.19-0.32; all p
      < 0.01). Relative ASM was also associated with trabecular volumetric bone mineral
      density (vBMD) at the femoral neck and spine (all p < 0.05), and trabecular bone
      volume to tissue volume (BV/TV), number (TbN), thickness (TbTh), and separation
      (TbSp) at the radius (all p <= 0.05). In all men, relative ASM was associated
      with CtTh at all sites (age- and physical activity-adjusted r = 0.17-0.28; all p
      < 0.01). Associations between relative ASM and trabecular vBMD at the spine in
      men were lost after adjusting for age; however, relative ASM was associated with
      trabecular vBMD at the femoral neck and TbN and TbSp at the radius (all p <
      0.01). We also investigated circulating factors associated with bone health that
      may be indicative of relative ASM and found that serum insulin-like growth factor
      (IGF) binding protein-2 (IGFBP-2) levels were the most robust negative predictors
      of relative ASM in both sexes. Collectively, these data add to the growing body
      of evidence supporting the highly-integrated nature of skeletal muscle and bone,
      and provide new insights into potential biomarkers that reflect the health of the
      musculoskeletal system.

PMID- 22623220
TI  - Mass transfer trends occurring in engineered ex vivo tissue scaffolds.
AB  - In vivo the vasculature provides an effective delivery system for cellular
      nutrients; however, artificial scaffolds have no such mechanism, and the ensuing
      limitations in mass transfer result in limited regeneration. In these
      investigations, the regional mass transfer properties that occur through a model
      scaffold derived from the human umbilical vein (HUV) were assessed. Our aim was
      to define the heterogeneous behavior associated with these regional variations,
      and to establish if different decellularization technologies can modulate
      transport conditions to improve microenvironmental conditions that enhance cell
      integration. The effect of three decellularization methods [Triton X-100 (TX100),
      sodium dodecyl sulfate (SDS), and acetone/ethanol (ACE/EtOH)] on mass transfer,
      cellular migration, proliferation, and metabolic activity were assessed. Results
      show that regional variation in tissue structure and composition significantly
      affects both mass transfer and cell function. ACE/EtOH decellularization was
      shown to increase albumin mass flux through the intima and proximate-medial
      region (0-250 MUm) when compared with sections decellularized with TX100 or SDS;
      although, mass flux remained constant over all regions of the full tissue
      thickness when using TX100. Scaffolds decellularized with TX100 were shown to
      promote cell migration up to 146% further relative to SDS decellularized samples.
      These results show that depending on scaffold derivation and expectations for
      cellular integration, specificities of the decellularization chemistry affect the
      scaffold molecular architecture resulting in variable effects on mass transfer
      and cellular response.

PMID- 22623221
TI  - Proteomic analysis of the lungs of mice infected with different pathotypes of
      H5N1 avian influenza viruses.
AB  - The virulence of influenza virus is determined by viral and host factors. Data on
      the genetic basis of the virulence of H5N1 influenza viruses have increased over
      the past decade; however, the contributions of host factors to the outcomes of
      H5N1 infection remain largely unknown. Here, we tested two chicken H5N1 viruses
      in mice and found that A/chicken/VN1214/2007 was nonlethal in mice and only
      replicated in the lung, whereas A/chicken/VN1180/2006 was highly lethal and
      replicated systemically in mice. To investigate the host response against these
      two different virus infections, we performed proteomic analysis by using 2D DIGE
      on the lung tissues of mice collected on days 1 and 3 postinoculation with
      different viruses or PBS as a control. Thirty-nine differentially expressed (DE)
      proteins related to "immune and stimulus response," "macromolecular biosynthesis
      and metabolism," and "cellular component and cytoskeleton" were identified in the
      virus-inoculated groups. Moreover, 13 DE proteins were identified between the two
      virus-inoculated groups, implying that these proteins may play important roles in
      the different outcomes of infection with these two viruses. Our data provide
      important information regarding the host response to mild and lethal H5N1
      influenza virus infection.

PMID- 22623222
TI  - Association of urinary 8-OHdG with lifestyle and body composition in elderly
      natural disaster victims living in emergency temporary housing.
AB  - OBJECTIVES: Residents who lost land and houses due to disasterous heavy rainfall
      related events on July 13, 2004 and the Chuetsu Earthquake on October 23, 2004
      were moved to emergency temporary housing. The change in life style due to living
      under such conditions is assumed to increase oxidative stress level. In this
      study, we investigated the oxidative stress level in elderly residents of
      emergency temporary housing, and analyzed its association with lifestyle and body
      composition following these disasters. METHODS: A noninvasive oxidative stress
      marker, urinary 8-hydroxydeoxyguanosine (8-OHdG), and body composition were
      measured in 73 elderly residents of emergency temporary housing. RESULTS: In the
      elderly female residents, the urinary 8-OHdG level tended to decrease with time
      after the disasters. 8-OHdG levels were slightly higher in females than males and
      significantly higher among those who exercised regularly compared to those who
      did not, particularly in females. A weak correlation was noted between the
      urinary 8-OHdG level and muscle ratio in females. CONCLUSIONS: The in vivo
      oxidative stress level in our study cohort of elderly residents of emergency
      temporary housing changed following the change in life style, but remained within
      the normal range. The increase in oxidative stress levels of elderly females was
      related to menopause. A decrease in estrogen levels due to menopause inhibits its
      antioxidant effects, which increases 8-OHdG levels. Although it is difficult to
      determine, a decrease in daily stressors over time following the disaster could
      be a cause of the decrease in oxidative stress levels. We suggest that the close
      evaluation of the stress level of disaster victims is desirable, in combination
      with evidence of antioxidative substances and the psychosocial influence of
      suffering as a consequence of the disaster.

PMID- 22623224
TI  - The Morris-Lecar neuron model embeds a leaky integrate-and-fire model.
AB  - We show that the stochastic Morris-Lecar neuron, in a neighborhood of its stable
      point, can be approximated by a two-dimensional Ornstein-Uhlenbeck (OU)
      modulation of a constant circular motion. The associated radial OU process is an
      example of a leaky integrate-and-fire (LIF) model prior to firing. A new model
      constructed from a radial OU process together with a simple firing mechanism
      based on detailed Morris-Lecar firing statistics reproduces the Morris-Lecar
      Interspike Interval (ISI) distribution, and has the computational advantages of a
      LIF. The result justifies the large amount of attention paid to the LIF models. 

PMID- 22623223
TI  - The effects of continuing and discontinuing smoking on the development of chronic
      kidney disease (CKD) in the healthy middle-aged working population in Japan.
AB  - OBJECTIVES: The strength of the association between smoking and the development
      of chronic kidney disease (CKD) in the healthy middle-aged working age population
      has not been established. METHODS: This was a retrospective 6-year observational
      study involving 4,121 male and 2,877 female workers who were free of primary
      kidney disease, diabetes mellitus, severe hypertension, and the signs and
      symptoms of CKD. Proteinuria was detected by a dipstick method, and glomerular
      filtration rate (GFR) was estimated by the equation of the Japan Society of
      Nephrology. RESULTS: Sixty men (1.5 %) and 21 women (0.7 %) developed proteinuria
      over the 6 years of the study. Irrespective of sex, in comparison with non
      smokers, those who continued smoking showed an odds ratio (OR) of 2.52 with a 95
      % confidence interval (CI) of 1.50-4.25 for developing proteinuria while those
      who quit smoking showed an OR of 1.29 (95 % CI 0.48-3.42), following adjustment
      for confounders. Among the study population, 443 men (10.7 %) and 356 women (12.4
      %) developed a GFR of <60 mL/min/1.73 m(2), corresponding to stage III CKD.
      Continuing smokers had a low OR (0.74, 95 % CI 0.60-0.90) for developing a low
      GFR, as well as a higher mean GFR than non-smokers. The reduction in GFR during
      the 6-year study period was not different between smokers and non-smokers, but it
      was larger in those who developed proteinuria than in those who did not,
      irrespective of smoking. CONCLUSIONS: Continuing smokers showed a twofold or more
      higher risk of developing proteinuria. Discontinuation of smoking substantially
      reduced the risk. A longer observational period may be required to detect the
      smoking-induced risk of developing stage III CKD in the middle-aged working
      population.

PMID- 22623225
TI  - Generation of alternating current in response to discontinuous illumination by
      photoelectrochemical cells based on photosynthetic proteins.

PMID- 22623226
TI  - Gonadectomy differentially regulates steroid receptor coactivator-1 and synaptic
      proteins in the hippocampus of adult female and male C57BL/6 mice.
AB  - Hippocampus is one of the most important structures that mediates learning and
      memory, cognition, and mental behaviors and profoundly regulated by sex hormones
      in a sex-specific manner, but the mechanism of underlying sex differences
      regulation is still unclear. We have previously reported that in the male and
      female mice, steroid receptor coactivator-1 (SRC-1) and some key synaptic
      proteins share similar developmental profile in the hippocampus, but how
      circulating sex hormones affect hippocampal SRC-1 as well as these synaptic
      proteins remain unclear. In this study, we examined how gonad sex hormones
      regulate hippocampal SRC-1, synaptophysin, PSD-95, and AMPA receptor subtype
      GluR1 by using immunohistochemistry and Western blot. The results showed that in
      the female mice, ovariectomy affected hippocampal SRC-1 and GluR1 were only
      detected at 2 weeks post operation, then it recovered to sham level;
      synaptophysin was unaffected at any timepoint examined; significant decrease of
      PSD-95 was only detected at 4 weeks post operation. However, in the male
      hippocampus, SRC-1 and PSD-95 were decreased from one week and lasted to 4 weeks
      after orchidectomy, GluR1 decreased from 2 weeks after orchidectomy, but
      synaptophysin remained unchanged as in the females. Correlation analysis showed
      the profiles of SRC-1 were positively correlated with GluR1 of the females, PSD
      95 and GluR1 of the males, respectively. The above results suggested a distinct
      regulatory mode between female and male gonad hormones in the regulation of
      hippocampal SRC-1 and synaptic proteins, which may be one of the mechanisms
      contributing to the dimorphism of hippocampus during development and ageing.

PMID- 22623227
TI  - Punch and spindle-shaped biopsies for collecting oral mucosal tissue for the
      fabrication of transplantable autologous epithelial cell sheets.
AB  - The oral mucosa is an easily accessible source of cells. Oral mucosal collection
      will be an essential surgical procedure for regenerative medicine and cell
      biological research. However, there is no current report that describes the
      details of the surgical procedure used for oral mucosal collection. Moreover, the
      number of cells that can be obtained has not been determined. Two different
      procedures, the punch biopsy and the spindle-shaped biopsy, were performed for
      the fabrication of transplantable autologous epithelial cell sheets. The mean
      values of the cells collected per square centimeter of tissue using the punch
      biopsy and the spindle-shaped biopsy were 76.8 +/- 45 * 10(4) cells/cm(2) and
      195.7 +/- 120 * 10(4) cells/cm(2), respectively. There was no significant
      difference between the punch biopsy and the spindle-shaped biopsy. The
      coefficient of variation of the punch biopsy and the spindle-shaped biopsy was
      58.9% and 69.8%, respectively. This result indicated that both procedures showed
      variations in the number of collected cells. Although the punch biopsy may be
      easier and simpler than the spindle-shaped biopsy, multiple punch biopsies may
      result in a more complicated procedure, and the spindle-shaped biopsy may be
      preferable when a large number of cells is necessary.

PMID- 22623228
TI  - Identification of C(6) -ceramide-interacting proteins in D6P2T Schwannoma cells.
AB  - Ceramide is a bioactive molecule involved in numerous cell signaling pathways
      that are associated with cell cycle control, differentiation, senescence, and
      apoptosis. Although substantial knowledge about ceramide-regulated pathways has
      accumulated in the past decade, molecular mechanisms of ceramide action remain
      poorly understood, primarily due to limited information about ceramide-binding
      proteins. In the present study, we used affinity purification with a synthetic
      biotin-conjugated C(6) -ceramide analogue and LC-MS/MS to identify potential
      ceramide-interacting proteins in D6P2T Schwannoma cells. The purification
      resulted in identification of 97 unique proteins. The identified proteins are
      involved in various cellular processes, including apoptosis, cellular stress,
      cell cycle, cell differentiation, signaling, transcription, translation, protein
      biogenesis, metabolism, and transport.

PMID- 22623230
TI  - Polyunsaturated omega-3 fatty acids improve responsiveness to clopidogrel after
      percutaneous coronary intervention in patients with cytochrome P450 2C19 loss-of
      function polymorphism.
AB  - BACKGROUND: Antiplatelet properties of omega-3 polyunsaturated fatty acids (PUFA)
      have been demonstrated in patients with coronary artery disease (CAD). It is
      unknown whether omega-3 PUFA can enhance platelet inhibition on standard aspirin
      and clopidogrel treatment in the setting of CYP2C19 loss-of-function
      polymorphism. AIM: To investigate whether omega-3 PUFA are able to modify
      platelet responsiveness to clopidogrel therapy in patients with CYP2C19 loss-of
      function polymorphism undergoing percutaneous coronary intervention (PCI).
      METHODS: 63 patients with stable CAD undergoing PCI (48 males, mean age 63.2 +/-
      9.6 years) were enrolled into an investigator- initiated, prospective, single
      centre, double-blind, placebo-controlled, randomised study. Patients on standard
      dual antiplatelet therapy (aspirin 75 mg daily and clopidogrel 600 mg loading
      dose followed by 75 mg daily) were assigned to receive the addition of 1 g of
      omega-3 ethyl esters (n = 33) or placebo (n = 30) for 1 month. Platelet function
      was measured serially by light transmittance aggregometry in response to 5 and 20
      MUmol/L ADP at baseline, 12 h, 3-5 days and 30 days after randomisation.
      CYP2C19*2 was genotyped at baseline. RESULTS: No significant differences were
      found in baseline variables, including the frequency of CYP2C19 genetic variants.
      At least one loss-of-function variant of CYP2C19*2 was found in 19 (30.2%)
      patients. In patients with CYP2C19*1/*2 and *2/*2 variants, maximal platelet
      aggregation induced by 5 and 20 MUmol/L ADP was reduced by 21.4% (p = 0.006) and
      14.3% (p = 0.041), respectively, after 1 month of treatment with omega-3 PUFA as
      compared to placebo. The beneficial effect of omega-3 PUFA was demonstrated in
      carriers of CYP2C19 loss-of-function polymorphism, whereas no differences in
      platelet aggregation between the omega-3 PUFA and placebo groups were found in
      patients with the 1*/1* variant. CONCLUSIONS: The addition of omega-3 ethyl
      esters significantly potentiates platelet response to clopidogrel after PCI
      mostly in patients with CYP2C19 loss-of-function polymorphism.

PMID- 22623231
TI  - [Omega-3--clopidogrel can help!].

PMID- 22623232
TI  - Microvolt T-wave alternans and other noninvasive predictors of serious arrhythmic
      events in patients with an implanted cardioverter-defibrillator.
AB  - BACKGROUND: Prediction of recurrent malignant ventricular tachyarrhythmias after
      insertion of a implantable cardioverter-defibrillator (ICD) is challenging.
      Microvolt T-wave alternans (MTWA) seems to be a promising marker of such events
      in ICD recipients. AIM: To assess prognostic significance of MTWA and other
      noninvasive parameters in the prediction of major arrhythmic events after ICD
      implantation. METHODS: This prospective study included 155 patients (121 male,
      age 59 +/- 11 years) in whom ICD was implanted for secondary prevention of a
      sudden cardiac death. In all patients, clinical evaluation along with estimation
      of ejection fraction, MTWA measurement using the HearTwave Cambridge Heart
      system, and determination of the corrected QT interval (QTc) and QT dispersion
      (QTd) based on resting ECG were performed 3 days before ICD implantation. Using
      24-h Holter monitoring, cardiac arrhythmias, QT interval, QT dynamicity, QT
      variability (QTSD) and heart rate variability (HRV) time domain parameters were
      determined. MTWA results were categorised, based on the accepted criteria, as
      positive, negative or indeterminate. In further analyses, positive and
      indeterminate MTWA results were grouped together as abnormal or non-negative
      tests [MTWA+], while negative MTWA results were considered normal [MTWA-]. During
      the follow-up (mean duration 21.6 +/- 11.6 months), major arrhythmic cardiac
      events (MACE), defined as death and/or the need for ablation and/or heart
      transplantation due to malignant ventricular tachyarrhythmias, were recorded.
      RESULTS: During the follow-up, MACE occurred in 17 (11%) patients. Abnormal MTWA
      before ICD implantation was found significantly more frequently in patients with
      MACE as compared to patients without MACE. Multivariate Cox regression analysis
      identified abnormal MTWA and QTSD as independent risk factors for MACE, with
      hazard ratios of 10.82 (95% CI 9.76-11.88; p< 0.05) and 1.08 (95% CI 1.05-1.08),
      respectively. Significant differences in MACE-free survival rate with regard to
      MTWA results (abnormal vs normal MTWA) were shown during the follow-up (p<
      0.001). The negative predictive value of normal MTWA for MACE was 98.6%. When
      both MTWA and QTSD were combined, the positive predictive value increased to 35%,
      with a sensitivity of 82% and specificity of 81%. The probability of MACE with
      normal results of both these tests was 2.3%. CONCLUSIONS: Abnormal MTWA is a
      strong independent predictor of MACE in ICD recipients, and QTSD is a weaker
      predictor. In the prediction of MACE after ICD implantation, the highest
      predictive value was noted for abnormal MTWA combined with QTSD. Normal values of
      these two parameters were associated with a low probability of MACE. These
      results suggest that standardised MTWA evaluation can be useful for risk
      stratification in the clinical practice.

PMID- 22623233
TI  - [Can MTWW be useful in qualifying patients for the ICD?].

PMID- 22623234
TI  - Initial troponin level may predict thrombus burden in patients with acute
      coronary syndrome. Optical coherence tomography study.
AB  - BACKGROUND: The major cause of acute coronary syndrome (ACS) is vessel thrombosis
      related to plaque rupture. Optical coherence tomography (OCT) is a feasible and
      effective technique to visualise a thrombus in vivo. AIM: To present the
      relationship between cardiac enzymes leakage before coronary angioplasty and
      thrombus visualised by OCT. METHODS: A population of 48 consecutive patients
      (mean age 64.8 +/- 9 years) with non ST elevation syndromes treated with primary
      coronary angioplasty was selected for the study. Angiographic and OCT
      quantitative assessment was performed for all patients, as well as qualitative
      thrombus assessment with a new index--the thrombus score (TS). Troponin I and
      creatine kinase and its MB fraction were measured for all patients at baseline
      and at least 6-8 hours after coronary angioplasty. RESULTS: The troponin level
      assessed before coronary angioplasty was 3.42 +/- 7.31 ng/dL. The mean TS
      assessed before coronary angioplasty was 96 +/- 56, and in 17 (35.4%) patients
      the score was greater than 100 points. Mean artery length occupied by thrombus
      was 7.8 +/- 3.8 mm. There was a significant correlation between troponin level
      and thrombus score (r = 0.44, p < 0.05) in the whole studied population.
      CONCLUSIONS: Initial troponin level may be associated with larger thrombus burden
      within a coronary artery. This finding may influence coronary flow and needs to
      taken into consideration during primary coronary intervention.

PMID- 22623235
TI  - [Optical coherent tomography--does this method have a future?].

PMID- 22623236
TI  - The role of B-type natriuretic peptide in the evaluation of left atrioventricular
      valve regurgitation following surgical repair of partial atrioventricular canal.
AB  - BACKGROUND: Left atrioventricular valve (LAVV) regurgitation usually follows
      surgical repair of partial atrioventricular canal (PAVC). Although measurements
      of B-type natriuretic peptide (BNP) levels are useful for the monitoring and
      prediction of outcomes in chronic mitral regurgitation, no data are available on
      the role of BNP measurements in the assessment of LAVV regurgitation in patients
      after surgical correction of PAVC. AIM: To determine the role of plasma BNP
      determination in the assessment of LAVV regurgitation in patients after surgical
      repair of PAVC. METHODS: We evaluated 41 patients who had undergone surgery for
      PAVC between 1968 and 2005 with preserved left ventricular ejection fraction
      (LVEF, mean age at follow-up: 39.2 +/- 14.0 years, mean age at the time of
      surgery: 31.3 +/- 15.6 years, 32 females) and 13 healthy controls (mean age: 38.9
      +/- 13.2 years, 9 females). All the subjects had undergone transthoracic
      echocardiography and had their plasma BNP levels determined. LAVV regurgitation
      was assessed qualitatively on 1+ to 4+ grading scale and quantitatively by
      calculating the effective regurgitant orifice area (EROA). RESULTS: LAVV
      regurgitation was present in 40 (97.6%) patients. Compared to patients with mild
      to-moderate LAVV regurgitation (grade 1+ to 2+/EROA < 0.4 cm2) evaluated
      qualitatively and quantitatively, the group with severe regurgitation (grade 3+
      to 4+/EROA >= 0.4 cm2) had higher values of left atrial volume (LAvol) and right
      ventricular (RV) systolic pressure, although there was no significant difference
      in plasma BNP levels. There were significant correlations between BNP levels and
      LAvol (r = 0.54, p = 0.0001), age at follow-up (r = 0.61, p=0.0001), age at the
      time of surgery (r = 0.58, p = 0.0001), RV diastolic diameter (r = 0.38, p =
      0.02) and RV systolic pressure (r = 0.48, p = 0.002). Multivariate logistic
      regression analysis showed that only LAvol and age at the time of surgery but not
      the degree of LAVV regurgitation were independently associated with elevated
      plasma BNP levels. CONCLUSIONS: In patients late after surgical repair of the
      PAVC with preserved LVEF, plasma BNP levels reflect the consequences of the shunt
      at atrial level and LAVV regurgitation expressed by LAvol but it does not allow
      to estimate the severity of regurgitation.

PMID- 22623237
TI  - [When should patients qualify for AV reoperation of the mitral valve after
      partial surgery of the common atrioventricular canal?].

PMID- 22623238
TI  - Morphological remarks regarding the structure of conduction system in the right
      ventricle.
AB  - BACKGROUND: The knowledge of conduction system morphology has a vital
      significance in cardiology and cardiac surgery - it enables to interpret
      pathologies and choose treatment. This has been confirmed by numerous accounts,
      both in the context of e.g. atrial fibrillation ablations as well as treating
      septum defects. Due to diversity and changeability of conduction system structure
      and their clinical implications, its thorough analyses seem to bear special
      importance. AIM: To examine the structure of selected elements of conduction
      system present in the right ventricle (RV). METHODS: Elements of conduction
      system present in RV of 6 foetuses (from 12 to 32 weeks of foetus age), 6
      children (from 1 day to 7-year-old) and 10 adults (from 37 to 79-year-old) were
      histologically examined. Cross sections of 10 moderator bands and 10 anterior
      papillary muscles of adult human hearts were made. Specimens including membranous
      and muscular parts of the septum along with diverging moderator band were taken
      from a group of foetus, child and adult hearts. Cuttings of 10 micron width were
      stained with Masson's method in Goldner's modification. On the basis of the
      sections of membranous and muscular parts of the septum, the continuities of the
      elements of the conduction system were analysed. RESULTS: It was observed that in
      most cases the right branch of His' bundle locates itself deep in the muscular
      tissue of the septum irrespective of age; it is clearly separate along its whole
      run and gradually penetrates the muscular tissue with its fibers. Hardly ever
      does the right branch of His' bundle locate itself on the surface,
      subendocardially, with a minimum penetration into the muscular tissue. Moreover,
      in most cases, elements of conduction system are present in moderator band. The
      main tissue constituting its stroma is above all muscular tissue and to a lesser
      extent, connective tissue. In addition to this, fat tissue in variable proportion
      was also observed. In cross sections of the moderator band a distinctively
      circumscribed stripe of fibers of the conduction system was found. However, one
      could also observe samples in which its identification was not possible.
      CONCLUSIONS: The right branch of His bundle within the muscular part of the
      septum in most cases is located intramuscularly irrespective of age. The results
      of analyses prove a relatively constant character of the presence of the
      conduction system within the moderator band.

PMID- 22623239
TI  - [Not one right arm has a name...].

PMID- 22623240
TI  - [Periprocedural and late complications after percutaneous closure of patent
      foramen ovale: a single centre experience].
AB  - BACKGROUND: Patent foramen ovale (PFO) is a potential risk factor for ischaemic
      stroke in young individuals. An interventional method of secondary stroke
      prevention in PFO patients is its percutaneous closure. AIM: To assess safety and
      effectiveness (i.e. lack of residual shunt) of percutaneous PFO closure in
      patients with history of cryptogenic cerebrovascular event. METHODS: 149 patients
      (56 men/93 women), aged 39 +/- 12 years, underwent percutaneous PFO closure. The
      implantation was performed under local anaesthesia, guided by trans-oesophageal
      echocardiography (TEE) and fluoroscopy. Follow-up trans-thoracic echocardiography
      (TTE) was performed at 1 month and follow-up TEE at 6-months. In cases of
      residual shunt, additional TEE was performed after ensuing 6 months. RESULTS:
      Effective PFO closure (no residual shunt) was achieved in 91.3% patients at 6
      months and 95.3% patients at 12 months. In 2 patients transient atrial
      fibrillation was observed during the procedure. In 2 patients, a puncture site
      haematoma developed and in 1 patient superficial thrombophlebitis was noted. In 1
      patient a small pericardial effusion was observed, which resolved at day 3 post
      procedurally, after administration of non-steroidal anti-inflammatory drugs.
      CONCLUSIONS: Percutaneous PFO closure seems to be a safe procedure when performed
      in a centre with adequate expertise with regard to these procedures.

PMID- 22623241
TI  - [Foramen ovale percutaneous closure in an adult patient: art or routine?].

PMID- 22623242
TI  - Transcatheter aortic valve implantation using direct aortic access: first
      procedures in Poland.
AB  - Transcatheter aortic valve implantation (TAVI) is an alternative option for the
      treatment of severe aortic stenosis in patients  carrying an elevated operative
      risk of conventional surgical aortic valve replacement (AVR). Recently, data from
      randomised  clinical trials confirmed superiority of TAVI when compared with the
      conservative treatment in inoperable patients, and its  non-inferiority when
      compared with AVR in a high-risk population.  Transfemoral vascular access
      remains the preferred route for delivering the bioprosthesis. However, in a
      significant proportion  of patients, the presence of severe iliac-femoral
      arteriopathy or small vessel diameter render the transfemoral approach  unusable.
      In this article, we report the first Polish experience of two successful TAVI
      procedures with bioprostheses (both  balloon- and self-expandable) delivered
      using direct aortic access.

PMID- 22623243
TI  - [New perspective in cardiac surgery].

PMID- 22623244
TI  - [Clinical improvement after physical training in patient with severe
      postinfarction heart failure, who underwent prosthetic heart valve implantation
      and numerous coronary interventional procedures].
AB  - The case of patient with advanced congestive heart failure, NYHA III, of
      ischaemic and valvular aetiology and concomitant  diseases is presented.
      Introduction of 6-month, controlled physical training resulted in improvement of
      health status, exercise  performance, ventilation and left ventricular function.
      Quality of life got significantly better. This aspect of treatment should  be
      considered in majority of patients with heart failure.

PMID- 22623245
TI  - Contrast-induced monoplegia following coronary angioplasty with iopromide.
AB  - Seizures, alterations in mental and cerebral functions, and ophthalmoplegia are
      known side effects of contrast agents. Here  we report a case of self-limiting
      monoplegia in a patient after the administration of intracoronary iopromide after
      coronary  angiography which emphasises that, although benign, contrast-induced
      monoplegia is a neurological disease which requires  careful evaluation and
      accurate management.

PMID- 22623246
TI  - The diagnosis and clinical importance of tumour neovascularisation from coronary
      artery to right atrial myxoma.
AB  - Myxomas are the commonest cardiac tumours and are usually localised in the atria.
      Neovascularisation in cardiac myxomas  has been shown in previous case reports.
      However, the clinical importance of neovascularisation in cardiac myxomas is not 
      well understood. In our case report, we present a right atrial myxoma in a 46
      year-old woman admitted to our hospital with  exertional angina and dyspnea.
      Coronary angiography revealed the presence of tumour neovascularisation from the
      right  coronary artery, with no evidence of coronary artery stenosis. We thus
      speculate that neovascularisation of myxoma may  cause typical anginal symptoms
      as a result of coronary steal phenomenon. Coronary angiography might help in the
      evaluation  of the neovascularisation process and also in indicating surgery.

PMID- 22623247
TI  - [Rotational angiography in monitoring of covered CP stent implantation in patient
      with critical aortic coarctation and patent ductus arteriosus].
AB  - In presented case rotational angiography with three dimensional reconstruction
      (3DRA) was used for diagnostic and control  angiograms during covered CP stent
      implantation in patient with critical aortic coarctation and patent ductus
      arteriosus.  Administering less contrast then for standard two perpendicular
      projections, good quality images were obtained in at least  seven projections.

PMID- 22623248
TI  - Cardiac chambers perforation by pacemaker and cardioverter-defibrillator leads.
      Own experience in diagnosis, treatment and preventive methods.
AB  - Cardiac chamber perforation is an uncommon, but potentially dangerous,
      complication of implantation of a pacemaker (PM)  or a cardioverter-defibrillator
      (ICD). Different clinical presentations are related to the time between
      implantation and perforation,  localisation of the perforation and concomitant
      lesions in neighbouring organs. Diagnosis is based on concomitant  analysis of
      the clinical picture, ECG tracings, PM or ICD function check-up with a
      programmer, and review of echocardiographic,  X-ray and computed tomography
      pictures. We analysed seven cases of perforation. Perforating leads were removed 
      in all cases and a new pacing system was implanted in five cases. Choice of
      operative technique (unscrewing and direct  traction from device pocket, Cook
      system or surgical procedure with pericardial drainage) depended on the time
      elapsing  between implantation and perforation, the presence of lesions of other
      organs, and the amount of fluid in the pericardial sac.  Avoiding unsafe
      localisation of a pacing electrode in the apex and free wall of the right
      ventricle and in the free anterolateral  wall of the right atrium, and avoiding
      leaving an extra length of pacing lead under tension and overscrewing of the lead
      helix  seem to be the best ways of prevention.

PMID- 22623249
TI  - [Statins 25 years in preventive cardiology].

PMID- 22623250
TI  - [Cardiovascular complication of cocaine abuse].

PMID- 22623251
TI  - [A large asymptomatic pericardial cyst in the apical region].
AB  - We presented a case of the large asymptomatic pericardial cyst localised near
      cardiac apex, filled with fluid of water-  -equivalent density. The cyst was
      detected accidentally during transthoracic echocardiography and confirmed by 64
      slice  multi-detector computed tomography. Repeated transthoracic
      echocardiography was recommened.

PMID- 22623252
TI  - [Ulcerated plaques of the aorta as a cause of ischaemic stroke].
AB  - Stroke is a second cause of mortality worldwide and a leading cause of acquired
      disability in adults. Approximately 20% of all  ischaemic strokes are of
      cardioembolic origin. We present a case of a 60-year-old man with a history of
      stroke without  changes in carotid and vertebral arteries. Echocardiography exam
      revealed patent foramen ovale (PFO) and abnormal echos  in the aorta that were
      verified as advanced complex atheromas by computed tomography. Due to small size
      PFO was  deemed insignificant and the source of embolism were most probably
      aortic atheromas. Patient was put on acenocumarol,  aspirin and statin.

PMID- 22623253
TI  - [Acquired pulmonary stenosis due to Hodgkin's lymphoma].
AB  - Acquired pulmonary stenosis is rare. When it occurs, it usually results from
      compression of pulmonary artery or heart by  a mediastinal tumours. Because these
      masses rarely cause compression, that produces murmurs, it's hard to make proper 
      diagnosis. We describe a 44 year-old woman with acquired pulmonary stenosis due
      to Hodgkin's lymphoma.

PMID- 22623254
TI  - [Acute myocardial infarction in pregnant woman].
AB  - The article presents a case of 30-year-old patient at her 30th week of pregnancy
      who was admitted to our clinic with non-ST  elevation myocardial infarction
      resulting from coronary artery embolism. A successful recanalisation of the
      occluded artery by  balloon angioplasty was performed.

PMID- 22623256
TI  - [Total left main coronary artery occlusion in a female patient after AVSD
      surgical repair in childhood as a cause of non ST elevation myocardial
      infarction].
AB  - A case of a 51-year-old woman with symptoms of non-ST-segment elevation acute
      coronary syndrome and concomitant  atrial flutter is presented. Patient underwent
      atrioventricular septal defect repair in childhood. Coronary angiography showed 
      total occlusion of left main coronary artery and massive collateral network
      originating from right coronary artery supplying  entire left coronary artery.
      Ablation of atrial flutter had been performed and patient was subsequently
      submitted to mitral  valve replacement, tricuspid valvuloplasty and coronary
      artery bypass grafting. The potential causes of left main occlusion are  in this
      case discussed.

PMID- 22623258
TI  - [Iatrogenic left lateral thoracic artery injury during pacemaker implantation
      successfully treated with stentgraft implantation].
AB  - Left lateral thoracic artery iatrogenic injury is a rare complication during
      pacemaker implantation procedure. We present  a case, where this complication
      occurred and was followed with massive tissue and pleural haemorrhage. The injury
      was  successfully sealed with stentgraft device without any complications.

PMID- 22623259
TI  - [Puncture of the subclavian vein--is it the fastest and safest form of vascular
      access in pacemaker implantation?].

PMID- 22623260
TI  - [Effectiveness of rehabilitation and endovascular intervention in patients with
      intermittent claudication due to peripheral arterial disease in the aorto-iliac:
      results of the CLEVER study].

PMID- 22623261
TI  - [Comparison of different methods for treating patients with intermittent
      claudication].

PMID- 22623263
TI  - [Polish power].

PMID- 22623264
TI  - Sphere-like fourth generation pseudo-dendrimers with a hyperbranched core.
AB  - A pseudo-dendritic structure clear of linear units is obtained from a
      hyperbranched aliphatic-aromatic polyester core modified by a B-protected AB(2)
      monomer. The chosen sequence of reaction and deprotection steps yields four
      generations of pseudo-dendrimers with either silyl- or OH-terminal units. (1)H
      and (13)C NMR confirm the extent of modification and the degree of branching in
      the different generations. The influence of generation number, end group type,
      and degree of branching on the specific solution behavior of the pseudo
      dendrimers is investigated by size-exclusion chromatography coupled to static
      light scattering and by intrinsic viscosity characterization. Apparent density
      and scaling parameters indicate increased compactness of the pseudo-dendrimers
      with increasing generation number.

PMID- 22623265
TI  - Reading aloud: the cumulative lexical interference effect.
AB  - Picture naming shows a cumulative semantic interference effect: Latency for
      naming a target picture increases as a function of the number of pictures
      semantically similar to the target that have previously been named (Howard,
      Nickels, Coltheart, & Cole-Virtue, Cognition 100:464-482, 2006). Howard and
      colleagues, and also Oppenheim, Dell, and Schwartz (Cognition 114:227-252, 2010),
      argued that this occurs because of the joint presence in the picture-naming
      system of three critical properties: shared activation, priming, and competition.
      They also discussed the possibility that whenever any cognitive system possesses
      these three properties, a cumulative similarity-based interference effect from
      repeated use of that cognitive system will occur. We investigated this
      possibility by looking for a cumulative lexical interference effect when the task
      is reading aloud: Will the latency of reading a target word aloud increase as a
      function of the number of words orthographically/phonologically similar to the
      target that have previously been read aloud? We found that this was so. This
      supports the general idea that cumulative similarity-based interference effects
      will arise whenever any cognitive system that possesses the three key properties
      of shared activation, priming, and competition is repeatedly used.

PMID- 22623266
TI  - Population pharmacokinetic analysis of risperidone and 9-hydroxyrisperidone with
      genetic polymorphisms of CYP2D6 and ABCB1.
AB  - This study estimated the population pharmacokinetics of risperidone and its
      active metabolite, 9-hydroxyrisperidone, according to genetic polymorphisms in
      the metabolizing enzyme (CYP2D6) and transporter (ABCB1) genes in healthy
      subjects. Eighty healthy subjects who received a single oral dose of 2 mg
      risperidone participated in this study. However, eight subjects with rare
      genotype variants in CYP2D6 alleles were excluded from the final model built in
      this study. We conducted the population pharmacokinetic analysis of risperidone
      and 9-hydroxyrisperidone using a nonlinear mixed effects modeling (NONMEM) method
      and explored the possible influence of genetic polymorphisms in CYP2D6 alleles
      and ABCB1 (2677G>T/A and 3435C>T) on the population pharmacokinetics of
      risperidone and 9-hydroxyrisperidone. A two-compartment model with a first-order
      absorption and lag time fitted well to serum concentration-time curve for
      risperidone. 9-hydroxyrisperidone was well described by a one-compartment model
      as an extension of the parent drug (risperidone) model with first-order
      elimination and absorption partially from the depot. Significant covariates for
      risperidone clearance were genetic polymorphisms of CYP2D6*10, including
      CYP2D6*1/*10 (27.5 % decrease) and CYP2D6*10/*10 (63.8 % decrease). There was
      significant difference in the absorption rate constant (k ( a )) of risperidone
      among the CYP2D6*10 genotype groups. In addition, combined ABCB1 3435C>T and
      CYP2D6*10 genotypes had a significant (P < 0.01) effect on the fraction of
      metabolite absorbed from the depot. The population pharmacokinetic model of
      risperidone and 9-hydroxyrisperidone including the genetic polymorphisms of
      CYP2D6*10 and ABCB1 3435C>T as covariates was successfully constructed. The
      estimated contribution of genetic polymorphisms in CYP2D6*10 and ABCB1 3435C>T to
      population pharmacokinetics of risperidone and 9-hydroxyrisperidone suggests the
      interplay of CYP2D6 and ABCB1 on the pharmacokinetics of risperidone and 9
      hydroxyrisperidone according to genetic polymorphisms.

PMID- 22623268
TI  - Evaluation and management of adrenal incidentaloma.
AB  - Adrenal incidentaloma is the most common adrenal neoplasm encountered in clinical
      practice. The timely, accurate, and cost-effective evaluation and management of
      adrenal lesions found incidentally can be challenging for clinicians. Evaluation
      begins with biochemical screening and additional imaging. Management strategies
      vary by patient factors and tumor characteristics. Adrenalectomy is indicated for
      lesions that are hormonally active, larger than 4-5 cm, symptom-related, and have
      an imaging appearance that is atypical of a benign lesion.

PMID- 22623267
TI  - Endothelial cell attachment and shear response on biomimetic polymer-coated
      vascular grafts.
AB  - Endothelial cell (EC) adhesion, shear retention, morphology, and hemostatic gene
      expression on fibronectin (FN) and RGD fluorosurfactant polymer (FSP)-coated
      expanded polytetrafluoroethylene grafts were investigated using an in vitro
      perfusion system. ECs were sodded on both types of grafts and exposed to 8
      dyn/cm(2) of shear stress. After 24 h, the EC retention on RGD-FSP-coated grafts
      was 59 +/- 14%, which is statistically higher than the 36 +/- 11% retention
      measured on FN grafts (p < 0.02). Additionally, ECs on RGD-FSP exhibited a more
      spread morphology and oriented in the direction of shear stress, as demonstrated
      by actin fiber staining. This spread morphology has been observed earlier in
      cells that are adapting to shear stress. Real-time PCR for vascular cell adhesion
      molecule 1, tissue factor, tissue plasminogen activator, and inducible nitric
      oxide synthase indicated that the RGD-FSP material did not activate the cells and
      that shear stress appears to induce a more vasoprotective phenotype, as shown by
      a significant decrease in VCAM-1 expression, compared with sodded grafts. RGD-FSP
      coating allows for a cell layer that is more resistant to physiological shear
      stress, as shown by the increased cell retention over FN. This shear stable EC
      layer is necessary for in vivo endothelialization of the graft material, which
      shows promise to increase the patency of synthetic small diameter vascular
      grafts.

PMID- 22623269
TI  - Family influences on mania-relevant cognitions and beliefs: a cognitive model of
      mania and reward.
AB  - OBJECTIVE: The present study proposed and tested a cognitive model of mania and
      reward. METHOD: Undergraduates (N = 284; 68.4% female; mean age = 20.99 years,
      standard deviation +/- 3.37) completed measures of family goal setting and
      achievement values, personal reward-related beliefs, cognitive symptoms of mania,
      and risk for mania. RESULTS: Correlational analyses and structural equation
      modeling supported two distinct, but related facets of mania-relevant cognition:
      stably present reward-related beliefs and state-dependent cognitive symptoms in
      response to success and positive emotion. Results also indicated that family
      emphasis on achievement and highly ambitious extrinsic goals were associated with
      these mania-relevant cognitions. Finally, controlling for other factors,
      cognitive symptoms in response to success and positive emotion were uniquely
      associated with lifetime propensity towards mania symptoms. CONCLUSIONS: Results
      support the merit of distinguishing between facets of mania-relevant cognition
      and the importance of the family in shaping both aspects of cognition.

PMID- 22623270
TI  - Identification and characterization of highly expressed proteins in sperm cells
      of the marine mussel Mytilus edulis.
AB  - Proteomic analysis on sperm has been restricted to only a few model organisms. We
      present here a 2DE PAGE proteome map of sperm cells from a nonmodel organism, the
      marine mussel Mytilus edulis, a free-spawning marine invertebrate with external
      fertilization. Ninety-six protein spots showing high expression were selected and
      of these 77 were successfully identified by nESI-MS analysis. Many of the
      identifications are relevant to sperm cell physiology and mtDNA functioning. The
      results and proteomics approach used are discussed in relation to their potential
      for advancing understanding of the unusual system of mtDNA inheritance described
      in Mytilus spp., and for the testing of evolutionary hypotheses pertaining to the
      role of fertilization in the speciation process.

PMID- 22623271
TI  - Is there subclinical enthesitis in early psoriatic arthritis? A clinical
      comparison with power doppler ultrasound.
AB  - OBJECTIVE: Enthesitis is a recognized feature of spondylarthritides (SpA),
      including psoriatic arthritis (PsA). Previously, ultrasound imaging has
      highlighted the presence of subclinical enthesitis in established SpA, but there
      are little data on ultrasound findings in early PsA. The aim of our study was to
      compare ultrasound and clinical examination (CE) for the detection of entheseal
      abnormalities in an early PsA cohort. METHODS: Forty-two patients with new-onset
      PsA and 10 control subjects underwent CE of entheses for tenderness and swelling,
      as well as gray-scale (GS) and power Doppler (PD) ultrasound of a standard set of
      entheses. Bilateral elbow lateral epicondyles, Achilles tendons, and plantar
      fascia were assessed by both CE and ultrasound, the latter scored using a
      semiquantitative (SQ) scale. Inferior patellar tendons were assessed by
      ultrasound alone. A GS SQ score of >1 and/or a PD score of >0 was used to
      describe significant ultrasound entheseal abnormality. RESULTS: A total of 24
      (57.1%) of 42 patients in the PsA group and 0 (0%) of 10 controls had clinical
      evidence of at least 1 tender enthesis. In the PsA group, for sites assessed by
      both CE and ultrasound, 4% (7 of 177) of nontender entheses had a GS score >1
      and/or a PD score >0 compared to 24% (9 of 37) of tender entheses. CE
      overestimated activity in 28 (13%) of 214 of entheses. All the nontender
      ultrasound-abnormal entheses were in the lower extremity. CONCLUSION: The
      prevalence of subclinical enthesitis in this early PsA cohort was low. CE may
      overestimate active enthesitis. The few subclinically inflamed entheses were in
      the lower extremity, where mechanical stress is likely to be more significant.

PMID- 22623272
TI  - A case of adult cannibalism in the gray mouse lemur, Microcebus murinus.
AB  - Cannibalism, defined as the eating of conspecific flesh, has been observed in a
      number of primate species, although it is still a relatively rare phenomenon. In
      cases where primates were seen feeding on an individual of the same species, the
      victims have exclusively been infants or juveniles. Here, I report an event of a
      free-living, adult male gray mouse lemur, Microcebus murinus, cannibalizing an
      adult conspecific female that died of an unknown cause. This observation has
      implications for the basic ecology of the species and highlights the potential
      for great flexibility in diet and behavior by a primate. This is, to my
      knowledge, the first communication of cannibalistic behavior in this species, as
      well as the first reported case of a nonhuman primate cannibalizing an adult
      conspecific.

PMID- 22623273
TI  - Cell surface proteome of the marine planctomycete Rhodopirellula baltica.
AB  - The surface proteome (surfaceome) of the marine planctomycete Rhodopirellula
      baltica SH1(T)  was studied using a biotinylation and a proteinase K approach
      combined with SDS-PAGE and mass spectrometry. 52 of the proteins identified in
      both approaches could be assigned to the group of potential surface proteins.
      Among them are some high molecular weight proteins, potentially involved in cell
      cell attachment, that contain domains shown before to be typical for surface
      proteins like cadherin/dockerin domains, a bacterial adhesion domain or the
      fasciclin domain. The identification of proteins with enzymatic functions in the
      R. baltica surfaceome provides further clues for the suggestion that some
      degradative enzymes may be anchored onto the cell surface. YTV proteins, which
      have been earlier supposed to be components of the proteinaceous cell wall of R.
      baltica, were detected in the surface proteome. Additionally, 8 proteins with a
      novel protein structure combining a conserved type IV pilin/N-methylation domain
      and a planctomycete-typical DUF1559 domain were identified.

PMID- 22623274
TI  - HLA-DRbeta1*04 typing by simple in-house PCR-SSP technique for rheumatoid
      arthritis patients.
AB  - A strong association between rheumatoid arthritis (RA) and human leukocyte
      antigen (HLA) has been observed in many different populations and that accounts
      for approximately one-third of the genetic component of RA susceptibility. The
      greatest effect comes from DRbeta1 gene where the strongest association has been
      found with DRbeta1*04 (DR4) allele. As serology has some disadvantages over
      polymerase chain reaction (PCR)-based techniques and commercially available PCR
      based kits are expensive, this study was aimed to standardize simple in-house PCR
      SSP technique. Accuracy of this test was further checked with standard PCR-SSOP
      (RLS) results. The frequency HLA-DRbeta1*04 was significantly increased among RA
      patients when compared with normal controls. In this study, a very simple,
      convenient and more cost-effective in-house PCR-SSP technique was standardized
      for HLA-DRbeta1*04 typing that is helpful to RA diagnosis in developing countries
      like India, which can be used as a good screening test.

PMID- 22623275
TI  - Aseptic meningitis: a rare side effect of cetuximab therapy.
AB  - Cetuximab, a chimeric IgG1 monoclonal antibody against the epidermal growth
      factor receptor, is indicated for the treatment of epidermal growth factor
      receptor-expressing metastatic colorectal cancer and recurrent or metastatic
      squamous cell cancer of the head and neck after failure of platinum-based
      therapy. The commonly reported side effects of cetuximab are infusion-related
      reactions, skin rash, fatigue, malaise and nausea. We report a case of aseptic
      meningitis developing as a rare side effect in a patient of stage IVB squamous
      maxillary cancer treated with cetuximab. To our knowledge, there have been very
      few cases of cetuximab-induced aseptic meningitis reported in literature.
      Clinicians should recognize that self-limiting aseptic meningitis can occur with
      administration of cetuximab. Our case report may serve as an additional reference
      for clinicians encountered with aseptic meningitis in the setting of using
      cetuximab.

PMID- 22623276
TI  - Economic impact of prescribing error prevention with computerized physician order
      entry of injectable antineoplastic drugs.
AB  - A cost-benefit analysis was carried out to determine the potential economic costs
      and benefits of pharmaceutical analysis in preventing prescribing errors for full
      standardized injectable antineoplastic drugs computerized physician order entry,
      in a pharmaceutical unit (University teaching hospital), compared with
      theoretical setting with no pharmaceutical analysis. The viewpoint is that of the
      payer or the French national Public Health Insurance system, and is limited to
      hospital cost (only direct medical costs related to net cost and net benefit. A
      decision analysis model was performed to compare two strategies: with
      pharmaceutical analysis (+/- pharmacy intervention) and without pharmaceutical
      analysis. RESULTS: are expressed in terms of benefit-to-cost ratio and total
      benefit. The robustness of the results was assessed through a series of one-way
      sensitivity analyses. Over 1 year, prescribing error incidence was estimated at
      1.5% [1.3-1.7], i.e. 218 avoided prescribing errors. Potential avoidance of
      hospital stay was estimated at 419 days or 1.9 +/- 0.3 days per prescribing
      error. Cost-benefit analysis could estimate a net benefit-to-cost ratio of 33.3
      (?17.34/?0.52) and a total benefit at ?16.82 per pharmaceutical analysis or
      ?249,844 per year. The sensitivity analysis showed robustness of results. Our
      study shows a substantial economic benefit of pharmaceutical analysis and
      intervention in the prevention of prescribing errors. The clinical pharmacist
      adds both value and economic benefit, making it possible to avoid additional use
      of expensive antineoplastic drugs and hospitalization. Computerized physician
      order entry of antineoplastic drugs improves the relevance of clinical pharmacist
      interventions, expanding pharmaceutical analysis and also the role of the
      pharmacist.

PMID- 22623277
TI  - Antibodies for profiling the human proteome-The Human Protein Atlas as a resource
      for cancer research.
AB  - In this review, we present an update on the progress of the Human Protein Atlas,
      with an emphasis on strategies for validating immunohistochemistry-based protein
      expression patterns and on the possibilities to extend the map of protein
      expression patterns for cancer research projects. The objectives underlying the
      Human Protein Atlas include (i) the generation of validated antibodies toward a
      major isoform of all proteins encoded by the human genome, (ii) creating an
      information database of protein expression patterns in normal human tissues, in
      cells, and in cancer, and (iii) utilizing generated antibodies and protein
      expression data as tools to identify clinically useful biomarkers. The success of
      such an effort is dependent on the validity of antibodies as specific binders of
      intended targets in applications used to map protein expression patterns. The
      development of strategies to support specific target binding is crucial and
      remains a challenge as a large fraction of proteins encoded by the human genome
      is poorly characterized, including the approximately one-third of all proteins
      lacking evidence of existence. Conceivable methods for validation include the use
      of paired antibodies, i.e. two independent antibodies targeting different and
      nonoverlapping epitopes on the same protein as well as comparative analysis of
      mRNA expression patterns with corresponding proteins.

PMID- 22623278
TI  - Developmental variation in ecogeographic body proportions.
AB  - While ecogeographic variation in adult human body proportions has been
      extensively explored, relatively less attention has been paid to the effect of
      Bergmann's and Allen's rules on human body shape during growth. The relationship
      between climate and immature body form is particularly important, as immature
      mortality is high, mechanisms of thermoregulation differ between young and mature
      humans, and immature body proportions fluctuate due to basic parameters of
      growth. This study explores changes in immature ecogeographic body proportions
      via analyses of anthropometric data from children included in Eveleth and
      Tanner's (1976) Worldwide Variation in Human Growth, as well as limb proportion
      measurements in eight different skeletal samples. Moderate to strong correlations
      exist between climatic data and immature stature, weight, BMI, and bi-iliac
      breadth; these relationships are as strong, if not stronger, in immature
      individuals as they are in adults. Correlations between climate and trunk height
      relative to stature are weak or nonexistent. Altitude also has significant
      effects on immature body form, with children from higher altitudes displaying
      smaller statures and lower body weights. Brachial and crural indices remain
      constant over the course of growth and display consistent, moderate correlations
      with latitude across ontogeny that are just as high as those detected in adults.
      The results of this study suggest that while some features of immature body form,
      such as bi-iliac breadth and intralimb indices, are strongly dictated by
      ecogeographic principles, other characteristics of immature body proportions are
      influenced by intrinsic and extrinsic factors such as nutrition and basic
      constraints of growth.

PMID- 22623279
TI  - Determinants of high weight gain and high BMI status in the first three months in
      urban Chinese infants.
AB  - OBJECTIVES: Investigate the potential factors associated with high weight gain
      and high BMI status in the first three months of life. METHODS: Totally, 930
      healthy neonates (489 boys and 441 girls) were involved in this community-based,
      prospective study in China. Data on body weight and length were collected at
      birth, and the 1st and 3rd months. A self-administered questionnaire was used to
      collect data regarding social demography, gestational status, delivery, and the
      feeding patterns of children. RESULTS: Prevalences of high BMI status (BMI = 85th
      p, re WHO BMI standards) increased over time in both sexes, reaching 24.5% and
      12.0% for boys and girls, respectively. General linear mixed models indicate high
      BMI status at 3 months is significantly and inversely associated with
      breastfeeding, as a proportion of feeding occasions [OR 0.74 (95%CI: 0.56-0.98)]
      and positively with lower birth weight [OR 2.07 (95%CI: 1.23-3.49)]. High weight
      gain (=85th p, re WHO velocity standards) in the first 3 months is also
      significantly associated with breastfeeding [OR 0.76 (95%CI: 0.59-0.96)] and sex,
      with boys at a higher risk than girls [OR 1.44 (95%CI: 1.07-1.97)]. Living in an
      extended family is associated with both high weight gain and high BMI status, but
      with marginal statistical significance. CONCLUSION: Analyses indicate an
      increasing trend of high BMI status in early infancy. Breastfeeding provides a
      protective effect for both high weight gain and high BMI status. The results
      concerning birth weight suggests a target for intervention.

PMID- 22623280
TI  - Enhanced osteoblast differentiation on scaffolds coated with TiO2 compared to
      SiO2 and CaP coatings.
AB  - The aim was to compare the protein release from normal human osteoblasts (NHO)
      cultured on scaffolds with similar morphology but different coatings. Different
      ceramic coatings; TiO(2), SiO(2) and calcium phosphate (CaP);
      Ca(9)HPO(4)(PO(4))(5)OH, were applied to porous TiO(2) scaffolds prepared by
      polymer sponge replication. NHO were cultured on scaffolds in triplicates. The
      concentration of cytokines and Ca(2+), and alkaline phosphatase (ALP) activity in
      the cell media was quantified. The secretion of osteopontin, osteoprotegerin,
      vascular endothelial growth factor and interleukin-6 was higher from NHO on
      TiO(2) compared to SiO(2) and CaP. The secretion from cells on the three
      scaffolds was, however, either similar or lower than the control cells cultured
      on plastic. The Ca(2+) concentration was higher in cell media on CaP the first
      week, and no difference in ALP activity was observed. TiO(2) coating induced a
      higher secretion of factors indicating enhanced osteoblast differentiation as
      compared to CaP and SiO(2).

PMID- 22623281
TI  - Tunable photoluminescence from graphene oxide.

PMID- 22623283
TI  - A novel wet extrusion technique to fabricate self-assembled microfiber scaffolds
      for controlled drug delivery.
AB  - We have developed a novel wet extrusion process to fabricate nonwoven self
      assembled microfiber scaffolds with uniform diameters less than 5 MUm and without
      any postmanipulation. In this method, a poly(L-lactic acid) solution flows
      dropwise into a stirring nonsolvent bath, deforming into liquid polymer streams
      that self-assemble into a nonwoven microfiber scaffold. The ability to tune fiber
      diameter was achieved by decreasing polymer spin dope concentration and
      increasing the silicon oil to petroleum ether ratio of the nonsolvent spin bath.
      To demonstrate the drug delivery capabilities of scaffolds, heparin was
      encapsulated using a conventional water-in-oil (W/O) emulsion technique and a
      cryogenic emulsion technique developed in our laboratory. Spin dope preparation
      was found to significantly effect the release kinetics of self-assembled
      scaffolds by altering the interconnectivity of pores within the precipitating
      filaments. After 35 days, scaffolds prepared from W/O emulsions released up to
      45% encapsulated heparin, whereas nearly 80% release of heparin was observed from
      cryogenic emulsion formulations. The versatility of our system, combined with the
      prolonged release of small molecules and the ability to control the homogeneity
      of self-assembling scaffolds, could be beneficial for many tissue regeneration
      and engineering applications.

PMID- 22623282
TI  - Receptors of garlic (Allium sativum) lectins and their role in insecticidal
      action.
AB  - Garlic (Allium sativum) lectins are promising candidate molecules for the
      protection against chewing (lepidopteran) as well as sap sucking (homopteran)
      insect pests. Molecular mechanism of toxicity and interaction of lectins with
      midgut receptor proteins has been described in many reports. Lectins show its
      effect right from sensory receptors of mouth parts by disrupting the membrane
      integrity and food detection ability. Subsequently, enter into the gut lumen and
      interact with midgut glycosylated proteins like alkaline phosphatase (ALP),
      aminopeptidase-N (APN), cadherin-like proteins, polycalins, sucrase, symbionin
      and others. These proteins play critical role in life cycle of insect directly or
      indirectly. Lectins interfere with the activity of these proteins and causes
      physiological disorders leading to the death of insects. Lectins further
      transported across the insect gut, accumulated in various body parts (like
      haemolymph and ovary) and interact with intracellular proteins like symbionin and
      cytochrome p450. Binding with cytochrome p450 (which involve in ecdysone
      synthesis) might interfere in the development of insects, which results in growth
      retardation and pre-mature death.

PMID- 22623284
TI  - Multifunctional nanocomposite based on graphene oxide for in vitro
      hepatocarcinoma diagnosis and treatment.
AB  - Because of its unique chemical and physical properties, graphene oxide (GO) has
      attracted a large number of researchers to explore its biomedical applications in
      the past few years. Here, we synthesized a novel multifunctional nanocomposite
      based on GO and systemically investigated its applications for in vitro
      hepatocarcinoma diagnosis and treatment. This multifunctional nanocomposite named
      GO-PEG-FA/Gd/DOX was obtained as the following procedures: gadolinium
      diethylenetriamine-pentaacetic acid-poly(diallyl dimethylammonium) chloride (Gd
      DTPA-PDDA) as magnetic resonance imaging (MRI) probe was applied to modify GO by
      simple physical sorption with a loading efficiency of Gd(3+) up to 0.314 mg mg(
      1). In order to improve its tumor targeting imaging and treatment efficiency, the
      obtained intermediate product was further modified with folic acid (FA). Finally,
      the nanocomposite was allowed to load anticancer drug doxorubicin hydrochloride
      via pi-pi stacking and hydrophobic interaction with the loading capacity reaching
      1.38 mg mg(-1). MRI test revealed that GO-PEG-FA/Gd/DOX exhibit superior tumor
      targeting imaging efficiency over free Gd(3+). The in vitro release of DOX from
      the nanocomposite under tumor relevant condition (pH 5.5) was fast at the initial
      10 h and then become relatively slow afterward. Moreover, we experimentally
      demonstrated that the multifunctional nanocomposite exhibited obviously cytotoxic
      effect upon cancer cells. Above results are promising for the next in vivo
      experiment and make it possible to be a potential candidate for malignancy early
      detection and specific treatment.

PMID- 22623285
TI  - The effects of the preferential dopamine D(3)  receptor antagonist S33138 on
      ethanol binge drinking in C57BL/6J mice.
AB  - The mesolimbic dopamine (DA) pathway plays an integral role in the reinforcing
      properties of many drugs of abuse, including alcohol (ethanol/EtOH). It has been
      reported that selective and acute blockade of the DA D3 receptor by SB-277011A
      will attenuate EtOH preference, intake, and lick responses in EtOH preferring
      rats. However, alcohol consumption that leads to abuse is often marked by binge
      drinking-which is characterized as bringing ones blood EtOH levels to >=80 mg/dL
      within 2 hours of the initial drink. It is unclear if brain mechanisms implicated
      in EtOH reward are equally implicated in EtOH binge consumption and abuse.
      Therefore, in this study, we examined the effect of the preferential D3 receptor
      antagonist S33138 on ethanol (6% v/v) and water consumption in male C57BL/6J mice
      using a restricted-access binge-drinking model. Ethanol drinking was not
      significantly altered by the intraperitoneal (i.p.) administration of 0.16 mg/kg
      of S33138. In contrast, the i.p. administration of 0.64 or 2.5 mg/kg i.p. of
      S33138 produced a significant decrease in ethanol consumption on days 1 and 7 and
      days 7-14 compared to vehicle treated animals. However, the mean water
      consumption was significantly decreased by (1) 0.16 and 0.64 mg/kg i.p. of S33138
      on Day 1 and (2) 2.5 mg/kg i.p. of S33138 at Days 1, 7, and 7-14. Our studies
      indicate that a low dose of S33138 significantly decreases binge drinking, and
      that it does not significantly alter the consumption of water. In addition,
      S33138 alone is not appetitive.

PMID- 22623286
TI  - Preoperative thrombocytosis is associated with survival after surgery for
      colorectal cancer.
AB  - OBJECTIVE: To evaluate the influence of preoperative thrombocytosis on survival
      after surgery in patients with colorectal cancer (CRC). METHODS: Four hundred
      fifty-three patients who had undergone CRC surgery were retrospectively
      identified from institutional database. On the basis of receiver operating
      characteristic (ROC) curve analysis, they were classified into two groups: group
      A, with a preoperative platelet count of <=300 (*10(9) /L), and Group B, with a
      preoperative platelet count of >300 (*10(9) /L). Uni- and multivariate analyses
      were performed to evaluate the relationship to overall survival. Kaplan-Meier
      analysis and log rank test were used to compare the survival curves between
      groups A and B. RESULTS: There was a significant difference in overall survival
      between the two groups (P = 0.007). Multivariate analysis of selected
      preoperative clinicolaboratory characteristics showed that overall survival was
      associated with the platelet count (Group A/B) (odds ratio, 1.642; 95% CI, 1.025
      2.629; P = 0.039) as well as the number of tumors (1/>=2), and the serum levels
      of C-reactive protein (CRP) and carcinoembryonic antigen (CEA). CONCLUSION:
      Preoperative thrombocytosis is associated with survival after surgery in CRC
      patients, and is able to divide such patients into two independent groups before
      surgery.

PMID- 22623287
TI  - Software for analysing ion mobility mass spectrometry data to improve peptide
      identification.
AB  - The development of ion mobility (IM) MS instruments has the capability to provide
      an added dimension to peptide analysis pipelines in proteomics, but, as yet,
      there are few software tools available for analysing such data. IM can be used to
      provide additional separation of parent ions or product ions following
      fragmentation. In this work, we have created a set of software tools that are
      capable of converting three dimensional IM data generated from analysis of
      fragment ions into a variety of formats used in proteomics. We demonstrate that
      IM can be used to calculate the charge state of a fragment ion, demonstrating the
      potential to improve peptide identification by excluding non-informative ions
      from a database search. We also provide preliminary evidence of structural
      differences between b and y ions for certain peptide sequences but not others.
      All software tools and data sets are made available in the public domain at
      http://code.google.com/p/ion-mobility-ms-tools/.

PMID- 22623288
TI  - Body mass index and the rheumatoid arthritis swollen joint count: an
      observational study.
AB  - OBJECTIVE: Obesity is a prevalent condition and a serious health concern. The
      relationship between obesity and rheumatoid arthritis (RA) disease activity and
      severity has not been adequately examined, and there are concerns that
      periarticular adipose tissue may reduce the utility of the joint examination.
      METHODS: We used a cross-sectional study to compare the performance of swollen
      joint count (SJC) in subjects with RA across body mass index (BMI) strata.
      Specifically, regression techniques tested for associations of SJC and 7 RA
      disease activity/severity measures (including high-sensitivity C-reactive protein
      level, radiographic changes, and Multidimensional Health Assessment Questionnaire
      scores) within BMI quartiles. We also evaluated the association of BMI with
      radiographic evidence of RA in multivariate analyses and the association of BMI
      with SJC. Clinical and laboratory data from 980 Veterans Affairs Rheumatoid
      Arthritis registry participants were analyzed using linear and logistic
      regression. RESULTS: Associations were evident between SJC and 6 of the 7
      examined RA disease activity/severity measures. SJC predicts RA disease
      activity/severity in more obese subjects at least as well as in subjects with
      lower BMIs, and there was a trend toward better performance in individuals with
      higher BMIs. Subjects with higher BMIs were marginally less likely to be
      characterized by radiographic changes (odds ratio 0.98, P = 0.051). We found no
      association between BMI and SJC. CONCLUSION: BMI does not obscure the
      relationship of SJC and objective disease activity measures. There is a
      borderline association of higher BMI and the likelihood of radiographic changes
      characteristic of RA after controlling for clinical characteristics.

PMID- 22623289
TI  - Proteome dynamics in primary target organ of infectious bursal disease virus.
AB  - Viruses induce dramatic changes in target tissue during pathogenesis, including
      host cellular responses that either limit or support the pathogen. The infectious
      bursal disease virus (IBDV) targets primarily the bursa of Fabricius (BF) of
      chickens, causing severe immunodeficiency. Here, we characterized the cellular
      proteome changes of the BF caused by IBDV replication in vivo using 2DE followed
      MALDI-TOF MS identification. Comparative analysis of multiple 2DE gels revealed
      that the majority of protein expression changes appeared between 24 and 96 h
      after IBDV infection. MS identified 54 altered cell proteins, 12 of which were
      notably upregulated by IBDV infection. Meanwhile, the other 42 cellular proteins
      were considerably suppressed by IBDV infection and are involved in protein
      degradation, energy metabolism, stress response, host macromolecular
      biosynthesis, and transport process. The upregulation of beta-actin and
      downregulation of dynamin during IBDV infection were also confirmed by Western
      blot and immunofluorescence analysis. These altered protein expressions provide a
      response profile of chicken BF to virulent IBDV infection. Further functional
      study on these altered proteins may lead to better understanding of pathogenic
      mechanisms of virulent IBDV infection and to new potential therapeutic targets.

PMID- 22623290
TI  - Evaluation of serum creatinine concentration-based glomerular filtration rate
      equations in pediatric patients with chronic kidney disease.
AB  - STUDY OBJECTIVE: To evaluate the accuracy of four equations based on serum
      creatinine concentration-the original Schwartz equation and the Leger, Bedside
      Chronic Kidney Disease in Children (CKiD), and Counahan-Barratt equations-for
      determining glomerular filtration rate (GFR) in pediatric patients with chronic
      kidney disease. DESIGN: Retrospective, observational, cross-sectional study.
      SETTING: Single-center, academic, outpatient pediatric nephrology clinic.
      PATIENTS: Fifty-three pediatric patients with stages 2-5 chronic kidney disease
      who completed GFR assessment with (125) I-iothalamate between January 2002 and
      January 2005. MEASUREMENT AND MAIN RESULTS: Data were collected from each
      patient's medical record. Glomerular filtration rate data were analyzed using 59
      evaluations from the 53 pediatric patients. (125) I-iothalamate clearance was
      used as the index GFR. The Bedside CKiD and Counahan-Barratt equations
      outperformed the Schwartz and Leger equations when the index GFR was less than 60
      ml/minute/1.73 m(2) ; the Schwartz and Counahan-Barratt equations performed best
      for index GFRs of 60 ml/minute/1.73 m(2)  or greater. Overestimation was highest
      with the Schwartz and Leger equations (> 20% index GFR in 57.6% and 62.7% of
      patients, respectively). Underestimation was highest with the Bedside CKiD and
      Counahan-Barratt equations (> 20% index GFR in 30.5% and 28.8%, respectively).
      CONCLUSION: The new Bedside CKiD equation performed well for pediatric patients
      with moderate-to-severe chronic kidney disease, but less well for pediatric
      patients with mild disease. Additional studies are needed to develop more precise
      GFR equations using serum creatinine concentration.

PMID- 22623291
TI  - Brief communication: Molar development and crown areas in early Australopithecus.
AB  - Recent studies suggest that the hypodigms representing the two earliest
      Australopithecus (Au. anamensis and Au. afarensis) form an ancestor-descendant
      lineage. Understanding the details of this possible transition is important
      comparative evidence for assessing the likelihood of other examples of ancestor
      descendant lineages within the hominin clade. To this end we have analyzed crown
      and cusp base areas of high resolution replicas of the mandibular molars of Au.
      anamensis (Allia Bay and Kanapoi sites) and those of Au. afarensis (Hadar,
      Laetoli, and Maka). We found no statistically significant differences in crown
      areas between these hypodigms although the mean of M(1) crowns was smaller in Au.
      anamensis, being the smallest of any Australopithecus species sampled to date.
      Intraspecies comparison of the areas of mesial cusps for each molar type using
      Wilcoxon signed rank test showed no differences for Au. anamensis. Significant
      differences were found between the protoconid and metaconid of Au. afarensis
      M(2)s and M(3)s. Furthermore, the area formed by the posterior cusps as a whole
      relative to the anterior cusps showed significant differences in Au. afarensis
      M(1)s and in Au. anamensis M(2)s but no differences were noted for M(3)s of
      either taxon. Developmental information derived from microstructural details in
      enamel shows that M(1) crown formation in Au. anamensis is similar to Pan and
      shorter than in H. sapiens. Taken together, these data suggests that the overall
      trend in the Au. anamensis-Au. afarensis transition may have involved a moderate
      increase in M(1) crown areas with relative expansion of distal cusps.

PMID- 22623293
TI  - Are urban Chinese infants gaining too much weight?

PMID- 22623292
TI  - Network analysis of reverse phase protein expression data: characterizing protein
      signatures in acute myeloid leukemia cytogenetic categories t(8;21) and inv(16).
AB  - Acute myeloid leukemia (AML) patients present with cancerous cells originating
      from bone marrow. Proteomic data on AML patient cells provides critical
      information on the key molecules associated with the disease. Here, we introduce
      a new computational approach to identify complex patterns in protein signaling
      from reverse phase protein array data. We analyzed the expression of 203 proteins
      in cells taken from AML patients. Dominant overlapping protein networks between
      subtypes of AML patients were characterized computationally, through a paired t
      test approach looking at relative protein expression. In the first application of
      this method, we compared recurrent cytogenetic abnormalities inv(16) and t(8;21),
      both affecting core-binding factor (CBFbeta), to normal CD34(+) cells and to each
      other. Six hundred seventy-eight sets of proteins were identified as
      significantly different in both inv(16) and t(8;21) compared to controls, at the
      Bonferroni number, alpha < 2.44 * 10(-6) . We strengthened our predictions by
      comparing results to those obtained using lasso regression analysis. Signaling
      networks were constructed from the protein pairs that were significantly
      different in the t-test and lasso regression analysis. Predicted networks were
      also compared to known networks from public protein-protein interaction and
      signaling databases. By characterizing unique "protein signatures" through this
      rapid computational analysis, and placing them in the context of canonical
      biological networks, we identify signaling pathways distinct to subcategories of
      AML patients.

PMID- 22623294
TI  - Pathways of carotenoid biosynthesis in bacteria and microalgae.
AB  - The carotenoids, a subfamily of the isoprenoids, are among the most widespread,
      ancient, diverse, and rich class of all natural products and biomolecules.
      Microorganisms, as well as microalgae and bacteria synthesize isoprenoids from
      isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP).
      For long time, mevalonic acid was assumed to be the only natural precursor for
      IPP and DMAPP in the cytosolic acetate/mevalonate pathway for the biosynthesis of
      sterols, sesquiterpenes, triterpenoids, and carotenoids. At present, it is
      accepted that the relatively new route, the methylerythritol 4-phosphate (MEP),
      or 1-deoxy-D: -xylulose-5-phosphate (DOXP) is the main pathway for the
      biosynthesis of plastidic isoprenoids, such as carotenoids, phytol (a side chain
      of chlorophylls), plastoquinone-9, isoprene, mono-, and diterpenes. Cytosolic
      isoprenoids (sterols) biosynthesized by MEP have been reported in eubacteria and
      algae (Chlorella, Chlamydomonas, Scenedesmus, and Dunaliella). This review
      summarizes current knowledge of the biosynthetic pathways leading to the
      formation of different isoprenoids and carotenoids in bacteria and microalgae.
      Particular attention was given to the last early steps of the biosynthesis of the
      key C(5)-precursor and the final steps of the biosynthesis of carotenoids
      including selected examples in microalgae and bacteria as well as the recent
      advances in genomics and metabolic engineering.

PMID- 22623295
TI  - Selection and taxonomic identification of carotenoid-producing marine
      actinomycetes.
AB  - Carotenoids are important pigments produced by plants and many microorganisms,
      including fungi, microalgae, cyanobacteria, and bacteria. Marine actinomycetes
      are a group of bacteria that produce a variety of metabolites with economic
      potential. Here, we describe a general method of selecting marine actinomycetes
      as carotenoids' producers. The screening is carried out at two levels: the first
      one involves a quick selection of strains by visual color inspection, and the
      second consists in the analysis of the extracts by HPLC. The taxonomic analysis
      of the producing strains gives us an overview of the groups of actinomycetes in
      which carotenoids can be found.

PMID- 22623296
TI  - Isolation, characterization, and diversity of novel radiotolerant carotenoid
      producing bacteria.
AB  - Carotenoids are natural pigments that exhibit many biological functions, such as
      antioxidants (i.e., promote oxidative stress resistance), membrane stabilizers,
      and precursors for vitamin A. The link between these biological activities and
      many health benefits (e.g., anticarcinogenic activity, prevention of chronic
      diseases, etc.) has raised the interest of several industrial sectors, especially
      in the cosmetics and pharmaceutical industries. The use of microorganisms in
      biotechnology to produce carotenoids is favorable by consumer and can help meet
      the growing demand for these bioactive compounds in the food, feed, and
      pharmaceutical industries. This methodological chapter details the development of
      a rapid and selective screening method for isolation and identification of
      carotenoid-producing microorganisms based on UV treatment, sequencing analysis of
      16S rRNA genes, and carotenoids' analysis using rapid and effective High
      Performance Liquid Chromatography-Diodearray-MS methods. The results of a
      comprehensive 16S rRNA gene-based phylogenetic analysis revealed a diversity of
      carotenoid-producing microorganisms (104 isolates) that were isolated at a high
      frequency from water samples collected at Misasa (Tottori, Japan), a region known
      for its high natural radioactivity content. These carotenoid-producing isolates
      were classified into 38 different species belonging to 7 bacterial classes
      (Flavobacteria, Sphingobacteria, alpha-Proteobacteria, gamma-Proteobacteria,
      Deinococci, Actinobacteria, and Bacilli). The carotenoids produced by the
      isolates were zeaxanthin (6 strains), dihydroxyastaxanthin (24 strains),
      astaxanthin (27 strains), canthaxanthin (10 strains), and unidentified molecular
      species that were produced by the isolates related to Deinococcus,
      Exiguobacterium, and Flectobacillus. Here, we describe the methods used to
      isolate and classify these microorganisms.

PMID- 22623297
TI  - A novel radio-tolerant astaxanthin-producing bacterium reveals a new astaxanthin
      derivative: astaxanthin dirhamnoside.
AB  - Astaxanthin is a red ketocarotenoid that exhibits extraordinary health-promoting
      activities such as antioxidant, anti-inflammatory, antitumor, and immune booster.
      The recent discovery of the beneficial roles of astaxanthin against many
      degenerative diseases such as cancers, heart diseases, and exercise-induced
      fatigue has raised its market demand as a nutraceutical and medicinal ingredient
      in aquaculture, food, and pharmaceutical industries. To satisfy the growing
      demand for this high-value nutraceuticals ingredient and consumer interest in
      natural products, many research efforts are being made to discover novel
      microbial producers with effective biotechnological production of astaxanthin.
      Using a rapid screening method based on 16S rRNA gene, and effective HPLC
      Diodearray-MS methods for carotenoids analysis, we succeeded to isolate a unique
      astaxanthin-producing bacterium (strain TDMA-17(T)) that belongs to the family
      Sphingomonadaceae (Asker et al., Appl Microbiol Biotechnol 77: 383-392, 2007). In
      this chapter, we provide a detailed description of effective HPLC-Diodearray-MS
      methods for rapid analysis and identification of the carotenoids produced by
      strain TDMA-17(T). We also describe the methods of isolation and identification
      for a novel bacterial carotenoid (astaxanthin derivative), a major carotenoid
      that is produced by strain TDMA-17(T). Finally, we describe the polyphasic
      taxonomic analysis of strain TDMA-17(T) and the description of a novel species
      belonging to genus Sphingomonas.

PMID- 22623298
TI  - Novel zeaxanthin-producing bacteria isolated from a radioactive hot spring water.
AB  - Zeaxanthin is a powerful antioxidant that is widely found in vegetables and
      fruits. Epidemiological evidences suggest that increasing the consumption of
      zeaxanthin in the diet is associated with a lower risk of age-related macular
      degeneration, helps prevent glaucoma and cataracts, and supports normal eye
      health. Zeaxanthin is a promising nutraceutical with many applications in the
      feed, food, and pharmaceutical industries. Currently, the commercial production
      of zeaxanthin is still dependant on synthetic routes with limitation for the
      biological one. Nevertheless, the biotechnological production of zeaxanthin is
      emerging due to its safety, potential large-scale production, and consumers'
      demand and preference for natural additives. Using a rapid screening method based
      on 16S rRNA gene and effective high-performance liquid chromatography (HPLC)
      Diodearray-MS methods for carotenoids' analysis, we isolated effective zeaxanthin
      producing bacteria (strain TDMA-5(T) and -16(T)) that belong to the family
      Sphingobacteriaceae and Sphingomonadaceae, respectively. In this chapter, we
      provide a detailed description of the HPLC-Diodearray-MS methods used for rapid
      analysis and identification of the carotenoids produced by both strains. In
      addition, the polyphasic taxonomic analysis of both novel strains and the
      description of a novel species and genus are described.

PMID- 22623299
TI  - Novel approach in the biosynthesis of functional carotenoids in Escherichia coli.
AB  - Many carotenoid pigments are present in a small quantity in nature or low
      yielding from their natural sources, despite these vivid colorations. Thus, the
      synthesis of useful carotenoids with metabolic pathway-engineered microorganisms
      should offer an alternative and promising approach for their efficient
      production. Here, we describe a novel method for an efficient production of such
      carotenoids, using E. coli cells that carry heterologous mevalonate pathway-based
      genes. This method also enables relevant researchers to efficiently identify the
      function of an isolated carotenogenic gene candidate. For example, the
      recombinant E. coli cells, which harbor a lycopene-producing plasmid, can
      synthesize 12.5 mg/g dry cell weight of lycopene with the addition of lithium
      acetoacetate to the medium. This level corresponded to an 11.8-fold increase of
      that of E. coli cells carrying only the lycopene-producing plasmid.

PMID- 22623300
TI  - Engineering Escherichia coli for canthaxanthin and astaxanthin biosynthesis.
AB  - Escherichia coli is a non-carotenogenic bacterium that could synthesize farnesyl
      pyrophosphate precursor through the isoprenoid pathway. Carotenoid production in
      E. coli requires heterologous expression of carotenoid synthesis genes. The
      carotenoid synthesis operons are assembled from genes isolated from carotenogenic
      bacterial sources. Expression of the different operons yields different
      carotenoid titers. The operons containing the idi gene give more than fivefold
      higher carotenoid titers than the operons lacking the idi gene. The carotenoid
      modification genes encoding ketolases and hydroxylases are incorporated into the
      operons for canthaxanthin and astaxanthin production. The ketolases and
      hydroxylases from different bacterial sources produce astaxanthin of different
      purity relative to the total carotenoids. Expression of the ketolases and
      hydroxylases closer to the promoter appears to give higher astaxanthin purity
      than expression farther from the promoter at the end of the operons. Balanced
      expression of ketolases and hydroxylases is critical to achieve high astaxanthin
      purity. Here, we describe methods to assemble carotenoid biosynthesis operons
      from carotenogenic gene clusters isolated from different bacterial sources and
      evaluate canthaxanthin or astaxanthin production in E. coli.

PMID- 22623301
TI  - Analysis of canthaxanthin production by Gordonia jacobaea.
AB  - Commercial interest in the use of natural pigments isolated from microorganisms
      has increased in recent years; hence, molecules belonging to the polyisoprenoid
      group (i.e., beta-carotene, astaxanthin, and canthaxanthin) have been the focus
      of much attention. The bacterium Gordonia jacobaea readily synthesizes and
      accumulates large amounts of canthaxanthin (beta-beta'-carotene-4,4'-dione),
      which is widely used in the food and cosmetics industries. In the present work,
      the integral process of canthaxanthin production by G. jacobaea is analyzed
      together with its application as natural sources for the industry. A great
      influence of culture media is observed on canthaxanthin levels. Also, the ability
      is found of extract the pigments with ethanol from bacteria. The concentration of
      the samples is a crucial point of the process, being mandatory to discard any
      process of heating the samples, because this provoked the pigment degradation.
      Despite this, the described method allows to consider G. jacobaea as a potential
      canthaxanthin producer for the industry.

PMID- 22623302
TI  - Isolation and light-stimulated expression of canthaxanthin and spirilloxanthin
      biosynthesis genes from the photosynthetic bacterium Bradyrhizobium sp. strain
      ORS278.
AB  - Some aerobic photosynthetic bacteria produce a cocktail of carotenoids, some of
      them being of a high economic value. A good example is the photosynthetic
      Bradyrhizobium sp. strain ORS278, which synthesizes, in addition to the
      photosynthetic carotenoid spirilloxanthin, large amounts of canthaxanthin. Here,
      we describe the procedures that have been successfully used to isolate the
      different crt genes involved in the synthesis of both carotenoids in this
      bacteria. The synthesis of these carotenoids is stimulated under far-red light by
      a bacteriophytochrome. The procedure we developed to study the effect of the
      light on carotenoids synthesis is also described. Finally, we describe a
      procedure to genetically transform photosynthetic Bradyrhizobium strain ORS278
      for improvement of canthaxanthin production.

PMID- 22623303
TI  - Construction of carotenoid biosynthetic pathways through chromosomal integration
      in methane-utilizing bacterium Methylomonas sp. strain 16a.
AB  - Methylomonas sp. strain 16a is an obligate methanotrophic bacterium that uses
      methane or methanol as the sole energy and carbon source. In order to engineer a
      stable strain to produce carotenoids, integration of genes or gene clusters in
      various nonessential locations in the chromosome is used. Construction of a
      canthaxanthin-producing strain involves the integration of canthaxanthin
      biosynthetic genes including the crtW gene for the beta-carotenoid ketolase.
      Addition of the crtZ gene that encodes the beta-carotenoid hydroxylase in this
      strain leads to the production of astaxanthin. Further increase in titer and
      yield for astaxanthin is obtained by integration of another set of astaxanthin
      biosynthetic gene cluster in a separate location of the chromosome.

PMID- 22623304
TI  - Genetic modification in Bacillus subtilis for production of C30 carotenoids.
AB  - C30 carotenoids, which have shorter backbones than C40 carotenoids, are known to
      be produced in the pathogenic bacterium Staphylococcus aureus that causes
      opportunistic infection. The first committed enzyme in the C30 carotenoid
      synthetic pathway is dehydrosqualene synthase CrtM. CrtM converts farnesyl
      pyrophosphate to dehydrosqualene. Dehydrosqualene desaturase CrtN then converts
      dehydrosqualene to the yellow C30 carotenoid, 4,4'-diaponeurosporene. This
      chapter describes a method to synthesize C30 carotenoids in Bacillus subtilis,
      which is generally recognized as a safe (GRAS) organism. Introduction of S.
      aureus crtM and crtN genes into B. subtilis results in yellow pigmentation. The
      B. subtilis transformant accumulates two C30 carotenoids, 4,4'-diapolycopene and
      4,4'-diaponeurosporene. Furthermore, together with crtMN, introduction of S.
      aureus crtP and crtQ genes, which encode mixed function oxidase and
      glycosyltransferase, respectively, donates the ability to produce glycosylated
      C30 carotenoic acid. Thus, carotenoid biosynthesis genes of S. aureus is
      applicable to genetically modify B. subtilis in order to construct a safe
      organism producing C30 carotenoids.

PMID- 22623305
TI  - Carotenoids' production from halophilic bacteria.
AB  - Carotenoids have received considerable attention due to their interesting
      industrial applications and, more importantly, their potential beneficial effects
      on human health. Halophiles comprise a heterogeneous group of microorganisms that
      need salts for optimal growth. The pigments produced by these halophilic
      organisms comprise phytoene, beta-carotene, lycopene, derivatives of
      bacterioruberin, and salinixanthin. Here, we describe the procedure to obtain
      salinixanthin from the extremely halophilic bacterium Salinibacter ruber.
      Additionally, we describe the expression of the beta-carotene biosynthetic genes
      crtE, crtY, crtI, and crtB from Pantoea agglomerans in the moderately halophilic
      bacterium Halomonas elongata obtaining a strain able to produce practically pure
      beta-carotene. Thus, the use of these halophilic microorganisms as a source of
      carotenoids constitutes an important commercial alternative in the production of
      carotenoids from biological sources.

PMID- 22623306
TI  - Construction and utilization of carotenoid reporter systems: identification of
      chromosomal integration sites that support suitable expression of biosynthetic
      genes and pathways.
AB  - In order to metabolically engineer microorganisms to produce compounds of
      interest, it is often desirable to integrate foreign genes into the chromosome of
      the host. However, the consequences of these genetic alterations are not always
      predictable. The use of a reporter system can often assist in determining
      chromosomal locations for optimal expression of foreign biosynthetic genes. The
      method described here involves the construction and utilization of promoterless
      carotenoid transposons, which provides a colorimetric screen for identifying the
      best chromosomal integration sites for the expression of the genes of interest.
      The transposons (pUTmTn5::392W and pUTmTn5::392) contain the carotenoid genes
      required for the production of canthaxanthin and astaxanthin, respectively. Thus,
      when promoterless transposons insert into the host's genome, the color of the
      colonies will vary based on their chromosomal location. There is a correlation
      between the color intensity of the colonies and the expression of the carotenoid
      transposon. The transposon insertion site can be determined via direct
      chromosomal sequencing. This sequence information is used to guide the site
      specific integration of biosynthetic genes and pathways of interest.

PMID- 22623307
TI  - Directed evolution of carotenoid synthases for the production of unnatural
      carotenoids.
AB  - Directed evolution is a well-established strategy to confer novel catalytic
      functions to the enzymes. Thanks to the relative ease of establishing color
      screening, carotenogenic enzymes can be rapidly evolved in the laboratory for
      novel functions. The combinatorial usages of the evolvants result in the creation
      of diverse set of novel, sometimes unnatural carotenoids. This chapter describes
      the directed evolution of diapophytoene (C(30) carotenoid) synthase CrtM to
      function in the foreign C(40) pathway, and the use of the CrtM variants thus
      obtained for the production of novel backbone structures.

PMID- 22623308
TI  - A high-throughput screen for the identification of improved catalytic activity:
      beta-carotene hydroxylase.
AB  - Astaxanthin is a natural product of immense value. Its biosynthesis has been
      investigated extensively and typically requires the independent activity of two
      proteins, a beta-carotene ketolase and beta-carotene hydroxylase. Rational
      engineering of this pathway has produced limited success with respect to the
      biological production of astaxanthin. Random mutagenesis of the beta-carotene
      ketolase has also been pursued. However, to date, no suitable method has been
      developed for the investigation of the beta-carotene hydroxylase because beta
      carotene and zeaxanthin cannot be differentiated visually, unlike beta-carotene
      and canthaxanthin. Thus, random mutagenesis and efficient selection of improved
      beta-carotene hydroxylase clones is not feasible. Presented here are the steps
      required for the efficient generation of a beta-carotene hydroxylase random
      mutagenesis library in Escherichia coli. Subsequently presented is a novel high
      throughput screening method for the rapid identification of clones with enhanced
      beta-carotene hydroxylase activity. The validity of the presented method is
      confirmed by functional expression of the mutated proteins, combined with
      accurate quantification of produced carotenoids. The developed method has
      potential applications in the development of biological systems for improved
      carotenoid biosynthesis, as well as robust astaxanthin production.

PMID- 22623309
TI  - DNA fingerprinting intron-sizing method to accomplish a specific, rapid, and
      sensitive identification of carotenogenic Dunaliella species.
AB  - Dunaliella salina has become the most important microorganism for the production
      of beta-carotene around the world. Natural carotenoids are a source of active
      metabolites utilized in different areas of food nutrition and pharmaceuticals,
      both in humans and also in animals. Identification of Dunaliella species from
      natural environments or certified culture collections is not precise and it is
      time consuming. However, accurate identification is extremely important because a
      slight difference in Dunaliella species generates great differences in
      carotenoids production. Here, we describe an intron-sizing method to make a rapid
      and precise identification for each of the most important carotenogenic species,
      showing that each hyperproducer species has an exclusive 18S rDNA fingerprint
      profile.

PMID- 22623310
TI  - Ketocarotenoid biosynthesis in transgenic microalgae expressing a foreign beta-C
      4-carotene oxygenase gene.
AB  - Ketocarotenoids are obtained by the action of the beta-carotene ketolase, which
      catalyses the addition of a keto-group at the C4 position of carotenoids beta-ion
      rings. Most microalgae and higher plants do not posses the carotene ketolase
      activity and consequently do not synthesize ketocarotenoids, which are highly
      demanded as feed supplements and as nutraceutical for human nutrition. Here we
      propose the use of the unicellular microalga Chlamydomonas reinhardtii to express
      the Bkt (beta-carotene ketolase) gene from Haematococcus pluvialis and synthesize
      a new ketocarotenoid that the vegetative cells of Chlamydomonas do not synthesize
      in the natural way. The methodology needed to successfully achieve metabolic
      engineering of ketocarotenoids synthesis in Chlamydomonas is described in this
      chapter, including the construction of a vector containing the Bkt gene,
      transformation of Chlamydomonas, selection of transformants, and carotenoids
      analysis.

PMID- 22623311
TI  - Characterization of carotenogenesis genes in the cyanobacterium Anabaena sp. PCC
      7120.
AB  - Cyanobacteria produce many kinds of carotenoids for light harvesting and light
      protection in photosynthesis. To elucidate the biosynthetic pathways of
      carotenoids in Anabaena sp. PCC 7120 (also known as Nostoc sp. PCC 7120), we have
      produced gene-disruption mutants lacking selected proposed carotenoid
      biosynthetic enzymes. Here we describe the construction of mutants by triparental
      mating. A cargo plasmid, bearing a target gene interrupted by an antibiotic
      resistant cassette, is transformed to E. coli donor containing a helper plasmid,
      and is introduced into Anabaena cells by conjugation. Double-reciprocal
      recombination replaces the target genes in Anabaena genome with mutated ones on
      the plasmid. Carotenoids in the selected double recombinants are identified using
      high-performance liquid chromatography.

PMID- 22623312
TI  - Obtaining lutein-rich extract from microalgal biomass at preparative scale.
AB  - Lutein extracts are in increasing demand due to their alleged role in the
      prevention of degenerative disorders such as age-related macular degeneration
      (AMD). Lutein extracts are currently obtained from plant sources, but microalgae
      have been demonstrated to be a competitive source likely to become an
      alternative. The extraction of lutein from microalgae posesses specific problems
      that arise from the different structure and composition of the source biomass.
      Here is presented a method for the recovery of lutein-rich carotenoid extracts
      from microalgal biomass in the kilogram scale.

PMID- 22623313
TI  - NMR-based isotopologue profiling of microbial carotenoids.
AB  - C-Isotopologue profiling is a powerful tool to determine on a quantitative basis
      the biosynthetic origin of carotenoids in microorganisms. To this aim, the
      carotenoid-producing microorganism is grown in medium containing (13)C-labeled
      glucose. After growth, the (13)C-isotopologue distribution in a given
      biosynthetic carotenoid is determined by quantitative NMR spectroscopy. The
      labeling pattern provides a fingerprint of processes involved in the metabolism
      of glucose and the formation of the carotenoid. For example, the (13)C-profile
      shows whether the isoprenoid precursors, isopentenyl diphosphate and
      dimethylallyl diphosphate, are formed by the mevalonate or the non-mevalonate
      pathway. The labeling data also specify the pathways of glucose utilization,
      e.g., via the Entner-Doudoroff pathway or glycolysis. The method is exemplified
      with the analysis of zeaxanthin biosynthesis in the Alphaproteobacterium,
      Paracoccus zeaxanthinifaciens.

PMID- 22623314
TI  - Analysis of diapocarotenoids found in pigmented Bacillus species.
AB  - Numerous carotenoid-producing Gram positive bacteria have now been identified.
      Their carotenoid profiles are typically complex with C(30) diapocarotenoid
      skeletons being modified by glucosidation and esterification. In the present
      article the protocols necessary to identify and quantify these diapocarotenoids
      are described. Bacillus species capable of forming spores will be used as generic
      examples and the associated procedures will cover the cultivation of the
      bacteria, extraction, chromatographic separations, and online detection by Photo
      Diode Array (PDA) and Mass Spectrometry (MS).

PMID- 22623315
TI  - Do substance use risk personality dimensions predict the onset of substance use
      in early adolescence? A variable- and person-centered approach.
AB  - Various studies found personality to be related to substance use, but little
      attention is paid to the role of personality risk dimensions with regard to an
      early onset of alcohol, tobacco, and marijuana use. Therefore, the current study
      used a variable-centered approach to examine whether anxiety sensitivity,
      hopelessness, sensation seeking, and impulsivity predict the onset of alcohol,
      tobacco, and marijuana use in early adolescence. Additionally, we adopted a
      person-centered approach to examine whether different personality subgroups could
      be identified, and whether these subgroups would be predictive of substance use.
      For that purpose, longitudinal data of a broader effectiveness study were used
      from 758 early adolescents (53 % female) aged 11-14 years. Structural equation
      models showed that hopelessness and sensation seeking were predictive of having
      ever used alcohol and tobacco. Also, sensation seeking was predictive of
      marijuana use. Latent profile analyses on the first wave data revealed a three
      profile solution for boys (i.e., resilients, internalizers, and externalizers)
      and a two-profile solution for girls (i.e., resilients and internalizers). In
      contrast to our expectation, further analyses revealed no significant differences
      in substance use between the different subprofiles for both boys and girls. The
      separate personality dimensions thus seem more relevant in predicting the onset
      of substance use compared to the personality profiles. However, the personality
      profiles might be informative in explaining more excessive substance use
      behaviors.

PMID- 22623316
TI  - A randomized trial of MBSR versus aerobic exercise for social anxiety disorder.
AB  - OBJECTIVE: Effective treatments for social anxiety disorder (SAD) exist, but
      additional treatment options are needed for nonresponders as well as those who
      are either unable or unwilling to engage in traditional treatments. Mindfulness
      based stress reduction (MBSR) is one nontraditional treatment that has
      demonstrated efficacy in treating other mood and anxiety disorders, and
      preliminary data suggest its efficacy in SAD as well. METHOD: Fifty-six adults
      (52% female; 41% Caucasian; age mean [M] +/- standard deviation [SD]: 32.8 +/-
      8.4) with SAD were randomized to MBSR or an active comparison condition, aerobic
      exercise (AE). At baseline and post-intervention, participants completed measures
      of clinical symptoms (Liebowitz Social Anxiety Scale, Social Interaction Anxiety
      Scale, Beck Depression Inventory-II, and Perceived Stress Scale) and subjective
      well-being (Rosenberg Self-Esteem Scale, Satisfaction with Life Scale, Self
      Compassion Scale, and UCLA-8 Loneliness Scale). At 3 months post-intervention, a
      subset of these measures was readministered. For clinical significance analyses,
      48 healthy adults (52.1% female; 56.3% Caucasian; age [M +/- SD]: 33.9 +/- 9.8)
      were recruited. MBSR and AE participants were also compared with a separate
      untreated group of 29 adults (44.8% female; 48.3% Caucasian; age [M +/- SD]: 32.3
      +/- 9.4) with generalized SAD who completed assessments over a comparable time
      period with no intervening treatment. RESULTS: A 2 (Group) x 2 (Time) repeated
      measures analyses of variance (ANOVAs) on measures of clinical symptoms and well
      being were conducted to examine pre-intervention to post-intervention and pre
      intervention to 3-month follow-up. Both MBSR and AE were associated with
      reductions in social anxiety and depression and increases in subjective well
      being, both immediately post-intervention and at 3 months post-intervention. When
      participants in the randomized controlled trial were compared with the untreated
      SAD group, participants in both interventions exhibited improvements on measures
      of clinical symptoms and well-being. CONCLUSION: Nontraditional interventions
      such as MBSR and AE merit further exploration as alternative or complementary
      treatments for SAD.

PMID- 22623317
TI  - Comparison of decellularization techniques for preparation of extracellular
      matrix scaffolds derived from three-dimensional cell culture.
AB  - Extracellular matrix (ECM) scaffolds derived from cultured cells have drawn
      increasing attention for use in tissue engineering. We have developed a method to
      prepare cultured cell-derived ECM scaffolds by combining three-dimensional cell
      culture, decellularization, and selective template removal. Cell-ECM-template
      complexes were first formed by culture of cells in a poly(lactic-co-glycolic
      acid) (PLGA) mesh template to deposit their own ECM. The complexes were
      subsequently decellularized to remove cellular components. Finally, the PLGA
      template was selectively removed to obtain the ECM scaffolds. Seven
      decellularization methods were compared for their decellularization effects
      during scaffold preparation. They were: freeze-thaw cycling (-80 degrees C, six
      times) with ammonia water (25 mM); 0.1% TritonTM X-100 (TX100) with 1.5M KCl
      aqueous solution; freeze-thaw cycling alone; ammonia water alone; TX100
      extraction; osmotic shock with 1.5M KCl; and freeze-thaw cycling with 3M NaCl.
      Among these methods, the methods of freeze-thaw cycling with NH(4) OH and TX100
      with 1.5M KCl showed the best effect on the removal of cellular components from
      the complexes, while the other five methods could only partially remove cellular
      components. The ECM scaffolds prepared by these two methods had similar gross
      appearances and microstructures. In vivo implantation of the ECM scaffolds
      prepared by these two methods induced mild host responses. The two
      decellularization methods were demonstrated to be effective for preparation of
      cultured cell-derived ECM scaffolds.

PMID- 22623318
TI  - Thermoresponsive assembly of charged gold nanoparticles and their reversible
      tuning of plasmon coupling.
AB  - Charged colloidal gold nanoparticles (AuNPs) can be assembled and disassembled in
      an aqueous solution in response to temperature change and display reversible
      thermoresponsive tuning of plasmon coupling. The reversible tuning was made
      possible by manipulating the electrostatic interaction through the temperature
      dependent zeta potential of the charged AuNPs (see the extinction spectra of a
      typical AuNP dispersion).

PMID- 22623319
TI  - Three-dimensional visualization of the cutaneous angiosome using angiography.
AB  - The purpose of this study was to establish the three-dimensional (3D)
      architecture of the cutaneous angiosome for assessment and design of the
      perforator flaps. Two fresh cadavers were injected with carboxymethyl cellulose
      (CMC)/lead oxide and computed tomography (CT) scanned before and after the
      injection. The various parts of the cutaneous and subcutaneous tissue derived
      from one of the injected cadavers were also CT scanned. Three-dimensional
      reconstruction of the cutaneous angiosome and the two flap designs were performed
      using Materialise's Interactive Medical Image Control System (MIMICS). Both the
      reconstructed cutaneous angiosomes and the digital flaps can be displayed
      independently or in conjunction with bones, source arteries, and skin. The 3D
      architecture of the cutaneous angiosome ensures clear display of the spatial
      location, distribution range, and anastomoses relationship of the cutaneous
      perforators. In addition, the caliber, length, and position of a particular
      source artery are illustrated in the exact spatial location. As a result, the
      technique provides visualization of the general area and the expandable direction
      of a respective flap. This technique has the potential to play an important role
      in assessing perforator blood supply territory and in the design of new flaps.

PMID- 22623320
TI  - Global profiling of proteolytically modified proteins in human metastatic
      hepatocellular carcinoma cell lines reveals CAPN2 centered network.
AB  - Proteolysis affects every protein at some point in its life cycle. Many
      biomarkers of disease or cancer are stable proteolytic fragments in biological
      fluids. There is great interest and a challenge in proteolytically modified
      protein study to identify physiologic protease-substrate relationships and find
      potential biomarkers. In this study, two human hepatocellular carcinoma (HCC)
      cell lines with different metastasis potential, MHCC97L, and HCCLM6, were
      researched with a high-throughput and sensitive PROTOMAP platform. In total 391
      proteins were found to be proteolytically processed and many of them were cleaved
      into persistent fragments instead of completely degraded. Fragments related to
      161 proteins had different expressions in these two cell lines. Through analyzing
      these significantly changed fragments with bio-informatic tools, several bio
      functions such as tumor cell migration and anti-apoptosis were enriched. A
      proteolysis network was also built up, of which the CAPN2 centered subnetwork,
      including SPTBN1, ATP5B, and VIM, was more active in highly metastatic HCC cell
      line. Interestingly, proteolytic modifications of CD44 and FN1 were found to
      affect their secretion. This work suggests that proteolysis plays an important
      role in human HCC metastasis.

PMID- 22623321
TI  - Review on proteomic analyses of benzo[a]pyrene toxicity.
AB  - Benzo[a]pyrene (BaP), a five-ring polycyclic aromatic hydrocarbon, is a well
      recognized environmental pollutant. Coal-processing waste products, petroleum
      sludge, asphalt, creosote, and tobacco smoke, all contain high levels of BaP.
      Exposure to BaP elicits many adverse biological effects, including tumor
      formation, immunosuppression, teratogenicity, and hormonal effects. In addition
      to the genetic damage caused by BaP exposure, several studies have indicated the
      disruption of protein-protein signaling pathways. However, contrary to the large
      number of studies on BaP-induced DNA damage, only few data have been gathered on
      its effects at the protein level. This review highlights all proteomic studies to
      date used for assessing the toxicity of BaP and its metabolites in various organ
      systems. It will also give an overview on the role proteomics may play to
      elucidate the mechanisms underlying BaP toxicity.

PMID- 22623322
TI  - Alginates induce differentiation and expression of CXCR7 and CXCL12/SDF-1 in
      human keratinocytes--the role of calcium.
AB  - Alginates from seaweed are used in chronic wound management, though the molecular
      and cellular effects of various alginate dressings are not well documented. We
      have developed ultrapure sodium-alginates from Pseudomonas fluorescens with
      different content and distribution of single guluronic acid (G) residues (0-45%
      G), and tested their biological activities on human primary keratinocytes (KCs).
      The alginates inhibited KC migration and induced expression of differentiation
      markers. The potency of the alginates correlated with the increasing percentage
      of single G residues. These findings were explained by different binding and
      release of ionic calcium (Ca++) from the alginates which subsequently triggered
      differentiation. Ca-free alginates had no effect on KC migration and
      differentiation, but the chemokine receptor CXCR7 was upregulated. Q-PCR revealed
      that also CXCL12/SDF-1, one of two known CXCR7-ligands, was induced by the
      alginates. Both CXCR7 and CXCL12-induction was dependent on the alginate G
      content, and highest upregulation was induced by an alginate with 19% single G
      residues. In the epidermis, CXCR7 expression was restricted to the basal layer.
      This study defines two biological effects of ultrapure alginates on KCs, both
      being dependent on the alginate structure, and being either dependent or
      independent of Ca.

PMID- 22623323
TI  - Handling the recurrent laryngeal nerve (RLN) in thyroid surgery: intraoperative
      versus postoperative knowledge of RLN function.

PMID- 22623324
TI  - Identification of rheumatoid arthritis patients using an administrative database:
      a Veterans Affairs study.
AB  - OBJECTIVE: The accuracy of the diagnosis is vital when administrative databases
      are used for pharmacoepidemiologic and outcome studies. Data pertaining to the
      utility of databases for rheumatoid arthritis (RA) are sparse and variable. We
      assessed the utility of various diagnostic algorithms to identify RA patients
      within the Veterans Health Administration (VHA) databases. METHODS: Using the
      International Classification of Diseases, Ninth Revision code for RA at 2 visits
      at least 6 months apart, we identified 1,779 patients between October 1, 1998 and
      September 30, 2009 in our local Veterans Affairs Medical Center (VAMC)
      administrative database. Disease-modifying antirheumatic drug (DMARD) use was
      ascertained from the pharmacy database. Cases were analyzed based on DMARD
      therapy and RA codes at clinic visits. A total of 543 patients' medical records,
      selected by stratification and random selection on the basis of their visits,
      were reviewed to ascertain the clinicians' diagnoses and clinical criteria
      documentation. Positive predictive values (PPVs) were calculated for various
      database case identification algorithms using diagnosis of RA by medical record
      review as the gold standard. RESULTS: The PPV for identification of RA with 2 RA
      codes 6 months apart was 30.9%. Addition of DMARD therapy increased the PPV to
      60.4%. The PPV further increased to 91.4% when having an RA code at the last VAMC
      rheumatology clinic visit criterion was added. An algorithm using only 2
      administrative RA codes 6 months apart had a low PPV for correctly identifying
      patients with RA in the VHA database. CONCLUSION: Including DMARD therapy and
      requiring an RA code at the last visit with a rheumatologist increased the
      performance of the data extraction algorithm.

PMID- 22623325
TI  - The empirical coverage of confidence intervals: point estimates and confidence
      intervals for confidence levels.
AB  - Many confidence intervals calculated in practice are potentially not exact,
      either because the requirements for the interval estimator to be exact are known
      to be violated, or because the (exact) distribution of the data is unknown. If a
      confidence interval is approximate, the crucial question is how well its true
      coverage probability approximates its intended coverage probability. In this
      paper we propose to use the bootstrap to calculate an empirical estimate for the
      (true) coverage probability of a confidence interval. In the first instance, the
      empirical coverage can be used to assess whether a given type of confidence
      interval is adequate for the data at hand. More generally, when planning the
      statistical analysis of future trials based on existing data pools, the empirical
      coverage can be used to study the coverage properties of confidence intervals as
      a function of type of data, sample size, and analysis scale, and thus inform the
      statistical analysis plan for the future trial. In this sense, the paper proposes
      an alternative to the problematic pretest of the data for normality, followed by
      selection of the analysis method based on the results of the pretest. We apply
      the methodology to a data pool of bioequivalence studies, and in the selection of
      covariance patterns for repeated measures data.

PMID- 22623326
TI  - In poor families, mothers' milk is richer for daughters than sons: a test of
      Trivers-Willard hypothesis in agropastoral settlements in Northern Kenya.
AB  - The Trivers-Willard hypothesis predicts the unequal parental investment between
      daughters and sons, depending on maternal condition and offspring reproductive
      potential. Specifically, in polygynous populations where males have higher
      reproductive variance than females, it predicts that mothers in good condition
      will invest more in sons, whereas mothers in poor condition will invest more in
      daughters. Previous studies testing this hypothesis focused on behavioral
      investment, whereas few examined biological investment. This study investigates
      the Trivers-Willard hypothesis on both behavioral and biological parental
      investment by examining breastfeeding frequencies and breast milk fat
      concentrations. Data from exclusively breastfeeding mothers in Northern Kenya
      were used to test hypotheses: Economically sufficient mothers will breastfeed
      sons more frequently than daughters, whereas poor mothers will breastfeed
      daughters more frequently than sons, and economically sufficient mothers will
      produce breast milk with higher fat concentration for sons than daughters,
      whereas poor mothers will produce breast milk with higher fat concentration for
      daughters than sons. Linear regression models were applied, using breastfeeding
      frequency or log-transformed milk fat as the dependent variable, and offspring's
      sex (son = 1/daughter = 0), socioeconomic status (higher = 1/lower = 0), and the
      sex-wealth interaction as the predictors, controlling for covariates. Our results
      only supported the milk fat hypothesis: infant's sex and socioeconomic status
      interacted (P = 0.014, n = 72) in their relation with milk fat concentration. The
      model estimated that economically sufficient mothers produced richer milk for
      sons than daughters (2.8 vs. 1.74 gm/dl) [corrected] while poor mothers produced
      richer milk for daughters than sons (2.6 vs. 2.3 gm/dl). Further research on milk
      constituents in relation to offspring's sex is warranted.

PMID- 22623327
TI  - Studying host cell protein interactions with monoclonal antibodies using high
      throughput protein A chromatography.
AB  - Protein A chromatography is typically used as the initial capture step in the
      purification of monoclonal antibodies produced in Chinese hamster ovary (CHO)
      cells. Although exploiting an affinity interaction for purification, the level of
      host cell proteins in the protein A eluent varies significantly with different
      feedstocks. Using a batch binding chromatography method, we performed a
      controlled study to assess host cell protein clearance across both MabSelect Sure
      and Prosep vA resins. We individually spiked 21 purified antibodies into null
      cell culture fluid generated with a non-producing cell line, creating mock cell
      culture fluids for each antibody with an identical composition of host cell
      proteins and antibody concentration. We demonstrated that antibody-host cell
      protein interactions are primarily responsible for the variable levels of host
      cell proteins in the protein A eluent for both resins when antibody is present.
      Using the additives guanidine HCl and sodium chloride, we demonstrated that
      antibody-host cell protein interactions may be disrupted, reducing the level of
      host cell proteins present after purification on both resins. The reduction in
      the level of host cell proteins differed between antibodies suggesting that the
      interaction likely varies between individual antibodies but encompasses both an
      electrostatic and hydrophobic component.

PMID- 22623328
TI  - Surrogate, friend or foe? The need for case studies of the use of surrogate
      outcomes in cost-effectiveness analyses.
AB  - We comment on a recent article by Hawkins et al. presenting different analytic
      approaches for the inclusion of surrogate and final outcomes in cost
      effectiveness analyses. This methodological case study provides a timely and
      valuable contribution to build on the debate about the use of evidence based on
      surrogate outcomes in health technology assessment.

PMID- 22623329
TI  - Cutting edge: IL-2 signals determine the degree of TCR signaling necessary to
      support regulatory T cell proliferation in vivo.
AB  - To ensure immune tolerance, regulatory T cell (Treg) numbers must be maintained
      by cell division. This process has been thought to be strictly dependent on the
      Treg TCR interacting with MHC class II. In this study, we report that Treg
      division does not absolutely require cell-autonomous TCR signaling in vivo,
      depending on the degree of IL-2-mediated stimulation provided. At steady state IL
      2 levels, Tregs require cell-autonomous TCR signaling to divide. However, when
      given exogenous IL-2 or when STAT5 is selectively activated in Tregs, Treg
      division can occur independently of MHC class II and TCR signaling. Thus,
      depending on the amount of IL-2R stimulation, a wide range of TCR signals
      supports Treg division, which may contribute to preservation of a diverse
      repertoire of Treg TCR specificities. These findings also have therapeutic
      implications, as TCR signaling by Tregs may not be required when using IL-2 to
      increase Treg numbers for treatment of inflammatory disorders.

PMID- 22623330
TI  - Proinflammatory mediators disrupt glucose homeostasis in airway surface liquid.
AB  - The glucose concentration of the airway surface liquid (ASL) is much lower than
      that in blood and is tightly regulated by the airway epithelium. ASL glucose is
      elevated in patients with viral colds, cystic fibrosis, chronic obstructive
      pulmonary disease, and asthma. Elevated ASL glucose is also associated with
      increased incidence of respiratory infection. However, the mechanism by which ASL
      glucose increases under inflammatory conditions is unknown. The aim of this study
      was to investigate the effect of proinflammatory mediators (PIMs) on the
      mechanisms governing airway glucose homeostasis in polarized monolayers of human
      airway (H441) and primary human bronchial epithelial (HBE) cells. Monolayers were
      treated with TNF-alpha, IFN-gamma, and LPS during 72 h. PIM treatment led to
      increase in ASL glucose concentration and significantly reduced H441 and HBE
      transepithelial resistance. This decline in transepithelial resistance was
      associated with an increase in paracellular permeability of glucose. Similar
      enhanced rates of paracellular glucose flux were also observed across excised
      trachea from LPS-treated mice. Interestingly, PIMs enhanced glucose uptake across
      the apical, but not the basolateral, membrane of H441 and HBE monolayers. This
      increase was predominantly via phloretin-sensitive glucose transporter (GLUT)
      mediated uptake, which coincided with an increase in GLUT-2 and GLUT-10
      abundance. In conclusion, exposure of airway epithelial monolayers to PIMs
      results in increased paracellular glucose flux, as well as apical GLUT-mediated
      glucose uptake. However, uptake was insufficient to limit glucose accumulation in
      ASL. To our knowledge, these data provide for the first time a mechanism to
      support clinical findings that ASL glucose concentration is increased in patients
      with airway inflammation.

PMID- 22623331
TI  - Differential requirement of RasGRP1 for gammadelta T cell development and
      activation.
AB  - gammadelta T (gammadeltaT) cells belong to a distinct T cell lineage that
      performs immune functions different from alphabeta T (alphabetaT) cells. Previous
      studies established that Erk1/2 MAPKs are critical for positive selection of
      alphabetaT cells. Additional evidence suggests that increased Erk1/2 activity
      promotes gammadeltaT cell generation. RasGRP1, a guanine nucleotide-releasing
      factor for Ras, plays an important role in positive selection of alphabetaT cells
      by activating the Ras-Erk1/2 pathway. In this article, we demonstrate that
      RasGRP1 is critical for TCR-induced Erk1/2 activation in gammadeltaT cells, but
      it exerts different roles for gammadeltaT cell generation and activation.
      Deficiency of RasGRP1 does not obviously affect gammadeltaT cell numbers in the
      thymus, but it leads to increased gammadeltaT cells, particularly CD4(-)CD8(+)
      gammadeltaT cells, in the peripheral lymphoid organs. The virtually unhindered
      gammadeltaT cell development in the RasGRP1(-/-) thymus proved to be cell
      intrinsic, whereas the increase in CD8(+) gammadeltaT cells is caused by non-cell
      intrinsic mechanisms. Our data provide genetic evidence that decreased Erk1/2
      activation in the absence of RasGRP1 is compatible with gammadeltaT cell
      generation. Although RasGRP1 is dispensable for gammadeltaT cell generation,
      RasGRP1-deficient gammadeltaT cells are defective in proliferation following TCR
      stimulation. Additionally, RasGRP1-deficient gammadeltaT cells are impaired to
      produce IL-17 but not IFNgamma. Together, these observations revealed that
      RasGRP1 plays differential roles for gammadelta and alphabeta T cell development
      but is critical for gammadeltaT cell proliferation and production of IL-17.

PMID- 22623332
TI  - alpha-Enolase expressed on the surfaces of monocytes and macrophages induces
      robust synovial inflammation in rheumatoid arthritis.
AB  - alpha-Enolase (ENO1) is a multifunctional glycolytic enzyme expressed abundantly
      in the cytosol. It has been implicated in autoimmune and inflammatory diseases.
      Serum Abs against ENO1 were reported in rheumatoid arthritis (RA). Cell-surface
      expression of ENO1 has been found to be increased rapidly in response to
      inflammatory stimuli, but its expression and function has not been reported in
      RA. In this study, we show that cell-surface expression of ENO1 is increased on
      monocytes and macrophages isolated from RA patients but not on those from
      osteoarthritis patients, and Ab against ENO1 can stimulate these cells to produce
      higher amounts of proinflammatory mediators, such as TNF-alpha, IL-1 alpha/beta,
      IFN-gamma, and PGE(2) via p38 MAPK and NF-kappaB pathway. The frequency of ENO1
      positive cells in synovial fluid mononuclear cells was higher than PBMCs. ENO1
      positive cells were also found in the inflamed synovium from RA patients and
      arthritic ankle tissues of mice with collagen-induced arthritis. Taken together,
      these findings suggest that Abs against ENO1 present in RA sera may stimulate
      monocytes and macrophages expressing cell-surface ENO1 and contribute to
      production of proinflammatory mediators during the effector phase of synovial
      inflammation.

PMID- 22623333
TI  - Degree of chemical functionalization of carbon nanotubes determines tissue
      distribution and excretion profile.
AB  - Getting rid of the tubes: An assessment of the retention of functionalized multi
      walled carbon nanotubes (MWNTs) in the organs of mice was carried out using
      single photon emission computed tomography and quantitative scintigraphy (see
      scheme). Increasing the degree of functionalization on MWNTs enhanced renal
      clearance, while lower functionalization promoted reticuloendethelial system
      accumulation.

PMID- 22623334
TI  - Weekly change in mindfulness and perceived stress in a mindfulness-based stress
      reduction program.
AB  - OBJECTIVE: The purpose of the study was to examine weekly change in self-reported
      mindfulness and perceived stress in participants who completed an 8-week course
      in mindfulness-based stress reduction (MBSR). METHOD: Participants were 87 adults
      with problematic levels of stress related to chronic illness, chronic pain, and
      other life circumstances (mean age = 49 years, 67% female) participating in MBSR
      in an academic medical center. They completed weekly self-report assessments of
      mindfulness skills and perceived stress. It was hypothesized that significant
      improvement in mindfulness skills would precede significant change in stress.
      RESULTS: Mindfulness skills and perceived stress both changed significantly from
      pretreatment to posttreatment. Significant increases in mindfulness occurred by
      the second week of the program, whereas significant improvements in perceived
      stress did not occur until week 4. Extent of change in mindfulness skills during
      the first three weeks predicted change in perceived stress over the course of the
      intervention. CONCLUSIONS: Evidence that changes in mindfulness precede changes
      in perceived stress in a standard MBSR course is consistent with previous studies
      suggesting that improvements in mindfulness skills may mediate the effects of
      mindfulness training on mental health outcomes.

PMID- 22623335
TI  - The lateral thoracic artery passing through duplicated axillary vein: a case
      report.
AB  - The axillary vein is a large-blood vessel that lies on the medial side to the
      axillary artery. The veins of the axilla are more abundant than the arteries and
      their variations were extremely common. During educational dissection, a rare
      form of the axillary vein accompanying arterial variation was founded in left arm
      of 70-year-old female cadaver. The axillary vein was divided into two large
      veins, anterior and posterior axillary veins according to their anatomical
      position. The lateral-thoracic artery arose from the second part of the axillary
      artery and passed through the gap of duplicated axillary vein. Before the lateral
      thoracic artery passed through the gap of duplicated axillary vein, the lateral
      thoracic artery gave-off an additional branch, which descended superficial to the
      anterior axillary vein. It surrounded the anterior axillary vein as annular form
      and the diameter of surrounded part of the anterior axillary vein became narrow.
      This novel case was reported and its clinical implications of such a variant were
      discussed.

PMID- 22623336
TI  - Crystallin distribution patterns in Litoria infrafrenata and Phyllomedusa
      sauvagei lenses.
AB  - The eye lens remains transparent because of soluble lens proteins known as
      crystallins. For years gamma-crystallins have been known as the main lens
      proteins in lower vertebrates such as fish and amphibians. The unique growth
      features of the lens render it an ideal structure to study ageing; few studies
      have examined such changes in anuran lenses. This study aimed to investigate
      protein distribution patterns in Litoria infrafrenata and Phyllomedusa sauvagei
      species. Lenses were fractionated into concentric layers by controlled
      dissolution. Water-soluble proteins were separated into high (HMW), middle (MMW)
      and low molecular weight (LMW) fractions by size-exclusion HPLC and constituents
      of each protein class revealed by 1DE and 2DE. Spots were selected from 2DE gels
      on the basis of known ranges of subunit molecular weights and pH ranges and were
      identified by MALDI-TOF/TOF MS following trypsin digestion. Comparable lens
      distribution patterns were found for each species studied. Common crystallins
      were detected in both species; the most prominent of these was gamma-crystallin.
      Towards the lens centre, there was a decrease in alpha- and beta-crystallin
      proportions and an increase in gamma-crystallins. Subunits representing taxon
      specific crystallins demonstrating strong sequence homology with zeta
      crystallin/quinone oxidoreductase were found in both L. infrafrenata and P.
      sauvagei lenses. Further work is needed to determine which amphibians have taxon
      specific crystallins, their evolutionary origins, and their function.

PMID- 22623337
TI  - Differential inhibitory effects of proton pump inhibitors on the metabolism and
      antiplatelet activities of clopidogrel and prasugrel.
AB  - The interaction between proton pump inhibitors (PPIs) and clopidogrel/prasugrel
      was investigated. The IC50 values of omeprazole, esomeprazole, lansoprazole,
      pantoprazole and rabeprazole on the metabolic ratios of 2-oxo
      clopidogrel/clopidogrel, H4 (the active metabolite of clopidogrel)/2-oxo
      clopidogrel and R-138727 (the active metabolite of prasugrel)/prasugrel
      thiolactone in human liver microsomes were determined. The antiplatelet
      activities of clopidogrel and prasugrel were measured with or without PPIs. As a
      result, most PPIs (except for pantoprazole) inhibited the formation of 2-oxo
      clopidogrel with IC50 values of 20-32 MUm and inhibited the formation of H4 with
      IC50 values of 6-20 MUm. PPIs inhibited the formation of R-138727 with IC50
      values of 9-25 MUm. Among the tested PPIs, omeprazole exhibited the highest
      inhibitory potency on the formation of H4. Omeprazole, esomeprazole and
      rabeprazole exhibited the highest inhibitory potencies on the formation of R
      138727. For platelet aggregation, omeprazole and lansoprazole show higher
      inhibitory effects on the antiplatelet activity of clopidogrel. On the other
      hand, omeprazole, esomeprazole and rabeprazole significantly decreased the
      antiplatelet activity of prasugrel thiolactone. These data indicate that PPIs
      differ in their effects of inhibiting the metabolism and antiplatelet activities
      of clopidogrel and prasugrel.

PMID- 22623339
TI  - Consistent estimation of zero-inflated count models.
AB  - Applications of zero-inflated count data models have proliferated in health
      economics. However, zero-inflated Poisson or zero-inflated negative binomial
      maximum likelihood estimators are not robust to misspecification. This article
      proposes Poisson quasi-likelihood estimators as an alternative. These estimators
      are consistent in the presence of excess zeros without having to specify the full
      distribution. The advantages of the Poisson quasi-likelihood approach are
      illustrated in a series of Monte Carlo simulations and in an application to the
      demand for health services.

PMID- 22623338
TI  - DLC coatings for UHMWPE: relationship between bacterial adherence and surface
      properties.
AB  - Development of intrinsically antibacterial surfaces is of key importance in the
      context of prostheses used in orthopedic surgery. This work presents a thorough
      study of several plasma-based coatings that may be used with this functionality:
      diamond-like carbon (DLC), fluorine-doped DLC (F-DLC), and a high-fluorine
      content-carbon-fluor polymer (CF(X)). The coatings were obtained by a radio
      frequency plasma-assisted deposition on ultra high molecular weight polyethylene
      (UHMWPE) samples and physicochemical properties of the coated surfaces were
      correlated with their antibacterial performance against collection and clinical
      Staphylococcus aureus and Staphylococcus epidermidis strains. The fluorine
      content and the relative amount of C-C and C-F bonds were controlled by X-ray
      photoelectron spectroscopy, and hydrophobicity and surface tension by contact
      angle measurements. Surface roughness was studied by Atomic Force Microscopy.
      Additional nanoidentation studies were performed for DLC and F-DLC coatings.
      Unpaired t test and regression linear models evaluated the adherence of S. aureus
      and S. epidermidis on raw and coated UHMWPE samples. Comparing with UHMWPE,
      DLC/UHMWPE was the least adherent surface with independence of the bacterial
      species, finding significant reductions (p <= 0.001) for nine staphylococci
      strains. Bacterial adherence was also significantly reduced in F-DLC/ UHMWPE and
      CFx/UHMWPE for six strains.

PMID- 22623340
TI  - Influence measures based on the volume of confidence ellipsoids for GEE.
AB  - The generalized estimating equations (GEE) derived by Liang and Zeger to analyze
      longitudinal data have been used in a wide range of medical and biological
      applications. To make regression a useful and meaningful statistical tool,
      emphasis should be placed not only on inference or fitting, but also on
      diagnosing potential data problems. Most of the usual diagnostics for linear
      regression models have been generalized for GEE. However, global influence
      measures based on the volume of confidence ellipsoids are not available for GEE
      analysis. This article presents an extension of these measures that is valid for
      correlated-measures regression analysis using GEEs. The proposed measures are
      illustrated by an analysis of epileptic seizure count data arising from a study
      of prograbide as an adjuvant therapy for partial seizures and some simulated data
      sets.

PMID- 22623341
TI  - Albumin 3'untranslated region facilitates increased recombinant protein
      production from Chinese hamster ovary cells.
AB  - Chinese hamster ovary (CHO) cells are used for recombinant protein production in
      the pharmaceutical industry but there is a need to improve expression levels. In
      the present work experiments were carried out to test the effectiveness of
      different 3'untranslated regions (3'UTRs) in promoting production of a naturally
      secreted luciferase. Seamless cloning was used to produce expression vectors in
      which Gaussia princeps luciferase coding sequences were linked to the human
      albumin, immunoglobulin or chymotrypsinogen 3'UTR. Stably transfected CHO cells
      expressing these constructs were selected. Luciferase activity in the culture
      medium was increased 2-3-fold by replacing the endogenous 3'UTR with the albumin
      3'UTR and decreased by replacement with immunoglobulin or chymotrypsinogen 3'UTR.
      Replacement of the native 3'UTR with the albumin 3'UTR led to a 10-fold increase
      in luciferase mRNA levels. Deletion analysis of the albumin 3'UTR showed that
      loss of nucleotides 1-50, which removed an AU-rich complex stem loop region,
      caused significant reductions in both luciferase protein expression and
      luciferase mRNA levels. The results suggest that recombinant protein expression
      and yield could be improved by the careful selection of appropriate 3'UTR
      sequences.

PMID- 22623342
TI  - The interplay between autonomy and dignity: summarizing patients voices.
AB  - Patients have to be respected with dignity as the masters of their own lives. The
      problem, however, is that autonomy may become so dominant and the fundamental
      value of caring in professional nursing that the patient's dignity is affected.
      The aim of this article is to point out some of the issues with the interplay
      between autonomy, also called self-management and dignity. Given voice to the
      patient perspective the background is provided by cases from research conducted
      through qualitative interviews with patients and expanded by summarizing
      empirical research concerning the interplay between autonomy and dignity. The
      search strategy and the research question gave five empirical research papers and
      three theoretical studies and concept analyses. A concise overview of the
      relevant research contains information about all the major elements of the
      studies. The background research and an interpretative summary address new issues
      to be taken into account in dignity conserving care. 

PMID- 22623344
TI  - Direct comparison of MS-based label-free and SILAC quantitative proteome
      profiling strategies in primary retinal Muller cells.
AB  - To better understand the involvement of retinal Muller glial (RMG) cells in
      retinal diseases, we phenotyped primary porcine RMGs in dependence of cultivation
      time using different quantitative proteomic strategies. A well-established LC
      MS/MS-based quantification method was employed: stable isotope labeling by amino
      acids in cell culture (SILAC) and directly compared to label-free (LF)
      quantifications, based on total peak intensities using two different programs
      (MaxQuant and Progenesis LC-MS). The overall numbers of detected proteins were
      largely similar (overlap of 1324 proteins), only a total of 173 proteins were
      significantly altered between the different culture conditions. However, among
      these, only 21 proteins were shared between the three analytical strategies.
      Hence, the majority of altered proteins only reached significance thresholds in
      one of the applied analyses with a larger overlap between the two LF approaches.
      Among the shared, differentially abundant proteins were known RMG markers as well
      as new proteins associated with glial cell transition. However, proteins
      correlated to cellular transitions and dedifferentiation were also found among
      the proteins only significant in one or two of the applied strategies.
      Consequently, the application of different quantification and analytical
      strategies could increase the analytical depths of proteomic phenotyping.

PMID- 22623343
TI  - Targeted delivery of vancomycin to Staphylococcus epidermidis biofilms using a
      fibrinogen-derived peptide.
AB  - This study reports on the use of a fibrinogen-derived peptide for the specific
      targeting and delivery of vancomycin to Staphylococcus epidermidis biofilms. One
      method by which S. epidermidis initially adheres to biomaterials uses the plasma
      protein fibrinogen as an intermediary, where the S. epidermidis surface protein
      SdrG binds to a short amino acid sequence near the amino terminus of the Bbeta
      chain of fibrinogen. We mimicked this binding interaction and demonstrated the
      use of a synthetic fibrinogen-based beta6-20 peptide to target and deliver
      vancomycin to S. epidermidis in vitro. The beta6-20 peptide was synthesized and
      labeled with a Nanogold probe, and its targeting capabilities were examined
      through the use of scanning electron microscopy. The Nanogold component was then
      replaced by vancomycin, utilizing a flexible, variable length poly(ethylene
      glycol) linker between the peptide and antibiotic to create the targeted
      vancomycin products, beta6-20-PEG(x) -VAN. Initial binding to surface adherent S.
      epidermidis was increased in a concentration-dependent manner relative to
      vancomycin for all equivalent concentrations >=4 MUg/mL, with targeted vancomycin
      content up to 22.9 times that of vancomycin alone. Retention of the targeted
      antibiotics was measured after an additional 24-h incubation period, revealing
      levels 1.3 times that of vancomycin. The results demonstrate the improved
      targeting and retention of vancomycin within a biofilm due to the incorporation
      of a specific targeting motif.

PMID- 22623345
TI  - Illuminating a neglected clinical issue: societal costs of interpersonal
      dependency and dependent personality disorder.
AB  - OBJECTIVES: To determine the degree to which patients with high levels of trait
      dependency or dependent personality disorder (DPD) engage in behaviors that harm
      themselves and others (e.g., domestic violence, child abuse). METHOD: Six domains
      of literature were reviewed: (a) dependency as a risk factor for physical
      illness; (b) health care utilization and expenditures; (c) global and domain
      specific functional impairment; (d) violence toward others; (e) victimization by
      others; and (f) self-harm. RESULTS: High levels of trait dependency and DPD are
      associated with elevated risk for physical illness, partner and child abuse, and
      suicidality, as well as with high levels of functional impairment and increased
      health care expenditure. CONCLUSIONS: Contrary to clinical lore, trait dependency
      and DPD are associated with behaviors that lead to myriad negative consequences
      for the dependent person, those close to them, and society as a whole. These
      patterns have noteworthy implications for assessment and treatment of dependent
      patients and suggest that DPD should be included as a diagnostic category in the
      Diagnostic and Statistical Manual of Mental Disorders Fifth Edition.

PMID- 22623346
TI  - Topological study of mechanistic diversity in conjugated fatty acid biosynthesis.

PMID- 22623347
TI  - Novel findings of the anatomy and variations of the axillary vein and its
      tributaries.
AB  - The anatomy and variations of the axillary vein has significant implications in
      various invasive procedures such as venous access, axillary block, arteriovenous
      fistula creation, axillary node dissection, breast augmentation, and other
      surgical procedures involving the axilla. To clarify the anatomy of the axillary
      vein and its tributaries, 40 cadaveric upper extremities were examined after
      dissection and were classified into several types according to the courses and
      terminations of brachial veins. The brachial veins ended separately (Type A;
      72.5%) or made a common brachial vein (Type B; 27.5%) to enter the basilic vein
      or the axillary vein. The basilic vein was absent in 5.0% of the specimens.
      Duplication of the axillary vein was observed in 17.5% of the specimens and the
      lateral venous channel running along the lateral wall of the axilla was observed
      in 40.0% of the specimens. The most common drainage vein of the deep brachial
      vein was the lateral brachial vein (67.5%). The anterior circumflex humeral vein
      also emptied into the lateral brachial vein in 67.5% of the specimens. The
      posterior circumflex humeral vein crossed posterior side of the brachial plexus
      to join either the axillary vein (45.0%) or subscapular vein (42.5%). Perforation
      of the lateral root of median nerve by a lateral brachial vein, a common brachial
      vein, or a venous channel was observed in 15.0% of the specimens. Other venous
      variations accompanying the variations of the axillary artery or the brachial
      artery are described herein. The clinical importance of these findings is
      described in the discussion.

PMID- 22623348
TI  - Proteomic analysis of spontaneous mutants of Lactococcus lactis: Involvement of
      GAPDH and arginine deiminase pathway in H2O2 resistance.
AB  - Lactococcus lactis, one of the most commonly used dairy starters, is often
      subjected to oxidative stress in cheese manufacturing. A comparative proteomic
      analysis was performed to identify the molecular modifications responsible for
      the robustness of three spontaneous H(2)O(2)-resistant (SpOx) strains. In the
      parental strain, glyceraldehyde-3-phosphate deshydrogenase (GAPDH) activity is
      ensured by GapB and the second GAPDH GapA is not produced in standard growth
      conditions. We showed that GapA was overproduced in the highly resistant SpOx2
      and SpOx3 mutants. Its overproduction in the MG1363 strain led to an increased
      H(2)O(2) resistance of exponential growing cells. Upon H(2)O(2) exposure, GapB
      was fully inactivated by oxidation in the parental strain. In SpOx mutants, it
      partly remained in the reduced form sustaining partially GAPDH activity. The
      analysis of gapA disruption in these SpOx strains indicated that additional
      unraveled mechanisms likely contribute to the resistance phenotype. In the SpOx1
      mutant, the arginine deiminase pathway was found to be upregulated and disruption
      of arcA or arcB genes abolished H(2)O(2) resistance. We concluded that arginine
      consumption was directly responsible for the SpOx1 phenotype. Finally, these
      results suggest that sustaining energy supply is a major way of leading to
      oxidative stress resistance in L. lactis.

PMID- 22623349
TI  - Effectiveness of self-management of low back pain: systematic review with meta
      analysis.
AB  - OBJECTIVE: To determine the effectiveness of self-management for nonspecific low
      back pain (LBP). METHODS: We performed a systematic review searching the Medline,
      Embase, CINAHL, PsycINFO, LILACS, PEDro, AMED, SPORTDiscus, and Cochrane
      databases from earliest record to April 2011. Randomized controlled trials
      evaluating self-management for nonspecific LBP and assessing pain and disability
      were included. The PEDro scale was used to assess the methodologic quality of
      included trials. Data were pooled where studies were sufficiently homogenous.
      Analyses were conducted separately for short- (less than 6 months after
      randomization) and long-term (at least 12 months after randomization) followup.
      Six criteria for self-management were used to assess the content of the
      intervention. RESULTS: The search identified 2,325 titles, of which 13 original
      trials were included. Moderate-quality evidence showed that self-management is
      effective for improving pain and disability for people with LBP. The weighted
      mean difference at short-term followup for pain was -3.2 points on a 0-100 scale
      (95% confidence interval [95% CI] -5.1, -1.3) and for disability was -2.3 points
      (95% CI -3.7, -1.0). The long-term effects were -4.8 (95% CI -7.1, -2.5) for pain
      and -2.1 (95% CI -3.6, -0.6) for disability. CONCLUSION: There is moderate
      quality evidence that self-management has small effects on pain and disability in
      people with LBP. These results challenge the endorsement of self-management in
      treatment guidelines.

PMID- 22623350
TI  - Gene expression during S. epidermidis biofilm formation on biomaterials.
AB  - Biomaterial-centered infections are initiated by adhesion of bacteria to an
      implant, followed by colonization and mature biofilm formation. Staphylococcus
      epidermidis is commonly identified as the cause of these device-centered
      infections. This study used an in vitro model to evaluate temporal changes in the
      expression of genes-icaADBC, agrBDCA, aap, and atle-that have been identified to
      play a role in the pathogenesis of S. epidermidis infections. Real-time reverse
      transcription-polymerase chain reaction was used to determine changes in gene
      expression from S epidermidis biofilm grown on polyurethanes (Elasthane 80A,
      hydrophobic) modified with polyethylene oxide (Elasthane 80A-6PEO, hydrophilic)
      and fluorocarbon (Elasthane 80A-6F, hydrophobic). In vitro expression of the ica
      locus, which is involved in initial adhesion and intracellular aggregation,
      increased up to 100-fold from 2 to 48 h, whereas gene expression for autolysin
      AtlE decreased slightly from 2 to 12 h, followed by a 10-fold increase by 48 h.
      Upregulation of the aap gene associated with bacterial accumulation and the agr
      quorum-sensing system was observed during biofilm formation over 48 h. In
      addition, no correlation was observed between S. epidermidis gene expression and
      biomaterial surface chemistry. This study used an in vitro model to demonstrate
      that enhanced expression of the atle, aap, agr, and ica genes plays an important
      role in initial foreign body colonization and potentially in the establishment of
      a device-associated infection.

PMID- 22623351
TI  - A selection of papers from the Twentieth European Workshop on Econometrics and
      Health Economics. Introduction.

PMID- 22623352
TI  - A revisited folding reporter for quantitative assay of protein misfolding and
      aggregation in mammalian cells.
AB  - Protein misfolding and aggregation play important roles in many physiological
      processes. These include pathological protein aggregation in neurodegenerative
      diseases and biopharmaceutical protein aggregation during production in mammalian
      cells. To develop a simple non-invasive assay for protein misfolding and
      aggregation in mammalian cells, the folding reporter green fluorescent protein
      (GFP) system, originally developed for bacterial cells, was evaluated. As a
      folding reporter, GFP was fused to the C-terminus of a panel of human copper/zinc
      superoxide dismutase (SOD1) mutants with varying misfolding/aggregation
      propensities. Flow cytometric analysis of transfected HEK293T and NSC-34 cells
      revealed that the mean fluorescence intensities of the cells expressing GFP
      fusion of SOD1 variants exhibited an inverse correlation with the
      misfolding/aggregation propensities of the four SOD1 variants. Our results
      support the hypothesis that the extent of misfolding/aggregation of a target
      protein in mammalian cells can be quantitatively estimated by measuring the mean
      fluorescence intensity of the cells expressing GFP fusion. The assay method
      developed herein will facilitate the understanding of aggregation process of SOD1
      variants and the identification of aggregation inhibitors. The method also has
      great promise for misfolding/aggregation studies of other proteins in mammalian
      cells.

PMID- 22623353
TI  - Bony integration of titanium implants with a novel bioactive calcium titanate
      (Ca4Ti3O10) surface treatment in a rabbit model.
AB  - Nowadays total joint replacement is an indispensable component of modern
      medicine. The surfaces characteristics of cementless prostheses may be altered to
      achieve an accelerated and enduring bony integration. Classic surface coatings
      bear the risk of loosening or flaking from the implant body. This risk is
      excluded by the chemical conversion of the naturally existing TiO(2) surface
      layer into calcium titanate. The aim of this experimental animal study was to
      investigate the bony integration of implants with a new calcium titanate surface
      (Ca(4)Ti(3)O(10)) compared with a conventional standard Ti6Al4V surface.
      Cylindrical implants, made of titanium alloy (Ti6Al4V) were implanted in both
      lateral femoral condyles of New Zealand white rabbits. In each animal, an implant
      with and without surface treatment was inserted in a blinded manner. Animals were
      sacrificed after 4, 12, and 36 weeks, respectively. The axial pull-off forces
      were determined for 25 animals using a universal testing machine (Zwick Z010,
      Ulm, Germany). Furthermore, a histological analysis of the bony integration of
      the implants was performed in 12 specimens. In general, the pull-off forces for
      untreated and treated implants increased with longer survival times of the
      rabbits. No significant difference could be shown after 4 weeks between treated
      and untreated implants. After 12 weeks, the treated implants revealed a
      statistical significant higher pull-off force. After 36 weeks, the pull-off
      forces for treated and untreated implants aligned again. Titanium implants
      treated with calcium titanate, may offer an interesting and promising implant
      surface modification for endoprosthetic implants. They might lead to an
      accelerated osseointegration of total hip and knee replacements.

PMID- 22623354
TI  - Comparative proteomic analysis reveals similar and distinct features of proteins
      in dry and wet stigmas.
AB  - Angiosperm stigma supports compatible pollen germination and tube growth,
      resulting in fertilization and seed production. Stigmas are mainly divided into
      two types, dry and wet, according to the absence or presence of exudates on their
      surfaces. Here, we used 2DE and MS to identify proteins specifically and
      preferentially expressed in the stigmas of maize (Zea Mays, dry stigma) and
      tobacco (Nicotiana tabacum, wet stigma), as well as proteins rinsed from the
      surface of the tobacco stigma. We found that the specifically and preferentially
      expressed proteins in maize and tobacco stigmas share similar distributions in
      functional categories. However, these proteins showed important difference
      between dry and wet stigmas in a few aspects, such as protein homology in "signal
      transduction" and "lipid metabolism," relative expression levels of proteins
      containing signal peptides and proteins in "defense and stress response." These
      different features might be related to the specific structures and functions of
      dry and wet stigmas. The possible roles of some stigma-expressed proteins were
      discussed. Our results provide important information on functions of proteins in
      dry and wet stigmas and reveal aspects of conservation and divergence between dry
      and wet stigmas at the proteomic level.

PMID- 22623355
TI  - Catalytic metathesis of conjugated diynes.

PMID- 22623356
TI  - ADAM17 activation in circulating neutrophils following bacterial challenge
      impairs their recruitment.
AB  - Neutrophil infiltration and bacterial clearance occur earlier in conditional
      knockout mice with leukocytes lacking the metalloprotease ADAM17 than in control
      mice. We investigated cell-intrinsic changes in neutrophils lacking ADAM17 and
      alterations in the inflammatory environment in conditional ADAM17 knockout mice
      to determine how the sheddase exerts its effects on neutrophil recruitment. In
      vivo analyses comparing control and ADAM17-deficient neutrophils revealed that
      the latter cells accumulated at increased levels in the inflamed mesenteric
      microvasculature and in the peritoneal cavity following bacterial challenge,
      indicating changes in their adhesive properties. Consistent with this, bacterial
      infection caused a marked down-regulation of L-selectin, an adhesion protein and
      substrate of ADAM17, from the surface of circulating neutrophils in control mice
      but not in conditional ADAM17 knockout mice. Neutrophils from gene-targeted mice
      with leukocytes expressing a noncleavable form of L-selectin also displayed a
      competitive advantage in the presence of control neutrophils when infiltrating a
      site of infection. Taken together, our findings reveal that impaired L-selectin
      shedding is a key mechanism underlying early neutrophil recruitment in
      conditional ADAM17 knockout mice during bacterial infection. Disrupting only the
      shedding of L-selectin, however, did not increase bacterial clearance, indicating
      that additional substrates also contribute to the detrimental role of ADAM17
      during severe infection.

PMID- 22623357
TI  - Directed migration of mouse macrophages in vitro involves myristoylated alanine
      rich C-kinase substrate (MARCKS) protein.
AB  - A role for MARCKS protein in directed migration of macrophages toward a
      chemoattractant was investigated. A peptide identical to the N-terminus of MARCKS
      (the MANS peptide), shown previously to inhibit the function of MARCKS in various
      cell types, was used. We investigated whether this MARCKS-related peptide could
      affect migration of macrophages, using the mouse macrophage-like J774A.1 cell
      line and primary murine macrophages. Both of these cell types migrated in
      response to the chemoattractants macrophage/MCPs, MCP-1 (25-100 ng/ml) or C5a (5
      20 ng/ml). Cells were preincubated (15 min) with MANS or a mis-sense control
      peptide (RNS), both at 50 MUM, and effects on migration determined 3 h after
      addition of chemoattractants. The movement and interactions of MARCKS and actin
      also were followed visually via confocal microscopy using a fluorescently labeled
      antibody to MARCKS and fluorescently tagged phalloidin to identify actin. MANS,
      but not RNS, attenuated migration of J774A.1 cells and primary macrophages in
      response to MCP-1 or C5a, implicating MARCKS in the cellular mechanism of
      directed migration. Exposure of cells to MCP-1 resulted in rapid phosphorylation
      and translocation of MARCKS from plasma membrane to cytosol, whereas actin
      appeared to spread through the cell and into cell protrusions; there was visual
      and biochemical evidence of a transient interaction between MARCKS and actin
      during the process of migration. These results suggest that MARCKS is involved in
      directed migration of macrophages via a process involving its phosphorylation,
      cytoplasmic translocation, and interaction with actin.

PMID- 22623359
TI  - A method for proteomic analysis of equine subchondral bone and epiphyseal
      cartilage.
AB  - Proteomic analyses of cartilage and, to a lesser extent, of bone have long been
      impaired because of technical challenges related to their structure and
      biochemical properties. We have developed a unified method based on phenol
      extraction, 2DE, silver staining, and subsequent LC-MS/MS. This method proved to
      be efficient to characterize the proteome of equine cartilage and bone samples
      collected in vivo. Since proteins from several cellular compartments could be
      recovered, our procedure is mainly suitable for in situ molecular physiology
      studies focused on the cellular content of chondrocytes, osteoblasts, and
      osteoclasts as well as that of the extracellular matrix, with the exception of
      proteoglycans. Our method alleviates some drawbacks of cell culture that can mask
      physiological differences, as well as reduced reproducibility due to
      fractionation. Proteomic comparative studies between cartilage and bone samples
      from healthy and affected animals were thus achieved successfully. This
      achievement will contribute to increasing knowledge on the molecular mechanisms
      underlying the physiopathology of numerous osteoarticular diseases in horses and
      in humans.

PMID- 22623360
TI  - Solving bottlenecks in data sharing in the life sciences.
AB  - The joint Open PHACTS/GEN2PHEN workshop on "Solving Bottlenecks in Data Sharing
      in the Life Sciences" was held in Volendam, the Netherlands, on September 19 and
      20, 2011, and was attended by representatives from academia, industry,
      publishing, and funding agencies. The aim of the workshop was to explore the
      issues that influence the extent to which data in the life sciences are shared,
      and to explore sustainability scenarios that would enable and promote "open" data
      sharing. Several key challenges were identified and solutions to each of these
      were proposed.

PMID- 22623361
TI  - Novel automated system for magnetic resonance imaging quantification of the
      inflamed synovial membrane volume in patients with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To introduce a novel automated method for the quantification of the
      inflamed synovial membrane volume (SV) using magnetic resonance imaging (MRI),
      and to investigate its feasibility and validity in patients with juvenile
      idiopathic arthritis (JIA). METHODS: The tool was tested on 58 patients with JIA
      and wrist involvement. Thirty-six patients had a 1-year MRI followup. MRI of the
      clinically more affected wrist was performed using a 1.5T scanner and a Flex
      small coil. An algorithmic approach, based on supervised voxel classification for
      automatic estimation of SV in a 3-dimensional MRI, was developed. The SV was
      estimated as the number of positively classified voxels and then normalized by
      the patient's body surface (NSV). Validation procedures included the analysis of
      reliability, construct validity, responsiveness to change, discriminant validity,
      and the predictive value. RESULTS: The agreement between the automated estimation
      of NSV and the manual measurements was excellent (intraclass correlation
      coefficient 0.93, 95% confidence interval 0.79-0.98). The automatic NSV
      demonstrated good construct validity by yielding strong correlations with local
      signs of disease activity and a moderate correlation with global physician
      assessment of disease activity and with the Rheumatoid Arthritis Magnetic
      Resonance Imaging Scoring system synovitis score. NSV showed a strong
      responsiveness to clinical change (standardized response mean values >1) and
      satisfactory discriminant validity. High baseline NSV (>4.6) had high predictive
      value (100%) with respect to erosive progression. CONCLUSION: The proposed
      automated method allowed reliable quantification of NSV, which represents a
      promising imaging biomarker of disease activity in JIA. The automated system has
      the potential to improve the longitudinal assessment of JIA and to predict
      progressive joint destruction.

PMID- 22623362
TI  - Influence of fourth generation poly(propyleneimine) dendrimers on blood cells.
AB  - Dendrimers provide many exciting opportunities for potential biomedical
      applications. However, owing to their positively charged surfaces,
      poly(propyleneimine) (PPI) dendrimers show toxic and haemolytic activities. One
      of the methods for masking the peripheral cationic groups is to modify them using
      carbohydrate residues. In this study, three types of the fourth generation PPI
      dendrimers-uncoated (PPI-g4), approximately 35% maltotriose (Mal-III)-coated (PPI
      g4-OS), and approximately 90% Mal-III-coated (PPI-g4-DS) were investigated by
      assessing their effects on red blood cell (RBC) haemolysis in samples of pure
      RBCs, RBCs in the presence of human serum albumin (HSA) or human plasma, and RBCs
      in whole blood. Lymphocyte proliferation and platelet (PLT) aggregation were also
      studied in the presence of various concentrations of dendrimers. Although all
      dendrimers examined affected all the blood cells studied, the unmodified PPI-g4
      had the most damaging effect. It caused high RBC haemolysis rates and PLT
      aggregation and greatly inhibited lymphocyte proliferation. These effects were
      caused by the cationic surface of this polymer. The modification of PPI-g4 with
      Mal-III reduced the effect of the dendrimer on all blood cells. The presence of
      HSA or plasma in the buffer containing the RBCs or RBC in whole blood
      significantly decreased the extent of dendrimer-driven haemolysis.

PMID- 22623363
TI  - A high-throughput assay for enzymatic polyester hydrolysis activity by
      fluorimetric detection.
AB  - A fluorimetric assay for the fast determination of the activity of polyester
      hydrolyzing enzymes in a large number of samples has been developed. Terephthalic
      acid (TPA) is a main product of the enzymatic hydrolysis of polyethylene
      terephthalate (PET), a synthetic polyester. Terephthalate has been quantified
      following its conversion to the fluorescent 2-hydroxyterephthalate by an iron
      autoxidation-mediated generation of free hydroxyl radicals. The assay proved to
      be robust at different buffer concentrations, reaction times, pH values, and in
      the presence of proteins. A validation of the assay was performed by analyzing
      TPA formation from PET films and nanoparticles catalyzed by a polyester hydrolase
      from Thermobifida fusca KW3 in a 96-well microplate format. The results showed a
      close correlation (R(2)  = 0.99) with those obtained by a considerably more
      tedious and time-consuming HPLC method, suggesting the aptness of the
      fluorimetric assay for a high-throughput screening for polyester hydrolases. The
      method described in this paper will facilitate the detection and development of
      biocatalysts for the modification and degradation of synthetic polymers. The
      fluorimetric assay can be used to quantify the amount of TPA obtained as the
      final degradation product of the enzymatic hydrolysis of PET. In a microplate
      format, this assay can be applied for the high-throughput screening of polyester
      hydrolases.

PMID- 22623364
TI  - The causes of the nasolabial crease: a histomorphological study.
AB  - There are two main conflicting theories on how the nasolabial crease is formed: a
      muscular theory and a fascial theory. The muscular theory states that the
      nasolabial crease is mainly formed by the musculodermal insertions of the lip
      elevator muscles. The fascial theory claims that the nasolabial crease is mainly
      formed by dense fibrous tissue and by the firm fascial attachments to the fascia
      of the lip elevator muscles. If the muscular theory was true, the musculodermal
      insertions of the facial muscles could be interrupted directly by intradermal
      injections of low doses of botulinum toxin. Eight cadavers who presented with
      bilateral nasolabial creases were enrolled in the study. The nasolabial creases
      were harvested from 14 facial halves in their entire lengths and breadths with 5
      mm medial and lateral rims. The horizontally cut samples were stained with
      hematoxylin-eosin (H&E) and Elastica van Gieson (EVG). Immunohistochemistry for
      the smooth muscle marker actin and the skeletal muscle marker desmin was also
      performed. In each of the nasolabial creases, numerous skeletal muscle fibers
      were found in the dermis, which confirmed the muscular theory of the cause of the
      nasolabial crease. In addition, muscle fibers were present in the dermis 4 mm
      medial and 4 mm lateral to the nasolabial crease, but the amounts were
      significantly less than the amount located directly in the crease. Botulinum
      toxin injected intradermally into the nasolabial crease might constitute a new
      treatment option to minimize or even eradicate the crease and the fold.

PMID- 22623365
TI  - An in vitro study of collagen hydrogel to induce the chondrogenic differentiation
      of mesenchymal stem cells.
AB  - It is controversial whether a biomaterial itself, rather than addition of any
      exogenous growth factor, could induce mesenchymal stem cells (MSCs) to
      differentiate into chondrogenic lineage, further to regenerate cartilage.
      Previous studies have shown that collagen-based hydrogel could induce MSCs to
      differentiate into chondrocytes in vivo but the in vitro studies only have a few
      reports. The evidence that biomaterials could induce chondrogenesis is not
      adequate. In this study, we tried to address whether type I collagen hydrogel has
      chondro-inductive capability in vitro and how this scaffold induces MSCs to
      generate cartilage tissue without exogenous growth factors in the culture medium.
      We encapsulated neonatal rabbit bone marrow mesenchymal stem cells (BMSCs) in
      type I collagen hydrogel homogeneously or implanted cell aggregates in hydrogel,
      and cultured them in nonchondrogenic inductive media. After at least 28 days
      culture, cells in the homogeneous group were tending to chondrogenic
      differentiation while cell density was high, and cells in the aggregate group
      have almost gone through chondrogenesis and formed neo-cartilage tissue with
      abundant specific extracellular matrix (ECM) deposition. These results indicate
      collagen hydrogel has inherent inductivity for the chondrogenic differentiation
      of BMSCs, and the optimum specification and tissue formation were accompanied
      with local high cell density. This research suggests a feasible strategy to
      induce the chondro differentiation of BMSCs independent of exogenous growth
      factors, which may greatly contribute to clinical cartilage regeneration.

PMID- 22623366
TI  - Proteomic analysis of the role of S-nitrosoglutathione reductase in
      lipopolysaccharide-challenged mice.
AB  - S-Nitrosoglutathione reductase (GSNOR) is a key regulator of protein S
      nitrosylation, the covalent modification of cysteine residues by nitric oxide
      that can affect activities of many proteins. We recently discovered that
      excessive S-nitrosylation from GSNOR deficiency in mice under inflammation
      inactivates the key DNA repair protein O(6) -alkylguanine-DNA alkyltransferase
      and promotes both spontaneous and carcinogen-induced hepatocellular carcinoma. To
      explore further the mechanism of tumorigenesis due to GSNOR deficiency, we
      compared the protein expression profiles in the livers of wild-type and GSNOR
      deficient (GSNOR(-/-) ) mice that were challenged with lipopolysaccharide to
      induce inflammation and expression of inducible nitric oxide synthase (iNOS). Two
      dimensional difference gel electrophoresis analysis identified 38 protein spots
      of significantly increased intensity and 31 protein spots of significantly
      decreased intensity in the GSNOR(-/-) mice compared to those in the wild-type
      mice. We subsequently identified 19 upregulated and 19 downregulated proteins in
      GSNOR(-/-) mice using mass spectrometry. Immunoblot analysis confirmed in GSNOR(
      /-) mice a large increase in the expression of the pro-inflammatory mediator
      S100A9, a protein previously implicated in human liver carcinogenesis. We also
      found a decrease in the expression of multiple members of the protein disulfide
      isomerase (PDI) family and an alteration in the expression pattern of the
      endoplasmic reticulum (ER) chaperones in GSNOR(-/-) mice. Furthermore, altered
      expression of these proteins from GSNOR deficiency was prevented in mice lacking
      both GSNOR and iNOS. In addition, we detected S-nitrosylation of two members of
      the PDI protein family. These results suggest that S-nitrosylation resulting from
      GSNOR deficiency may promote carcinogenesis under inflammatory conditions in part
      through the disruption of inflammatory and ER stress responses.

PMID- 22623367
TI  - Screening for signs and symptoms of rheumatoid arthritis by family physicians and
      nurse practitioners using the Gait, Arms, Legs, and Spine musculoskeletal
      examination.
AB  - OBJECTIVE: To evaluate the sensitivity and specificity of the Gait, Arms, Legs,
      and Spine (GALS) examination to screen for signs and symptoms of rheumatoid
      arthritis (RA) when used by family physicians and nurse practitioners. METHODS:
      Participating health care professionals (2 rheumatologists, 3 family physicians,
      and 3 nurse practitioners) were trained to perform the GALS examination by
      viewing an instructional DVD and attending a training workshop. One week after
      training, the health care professionals performed the GALS examination on 20
      individuals with RA and 21 individuals without RA. All participants were
      recruited through 2 rheumatology practices, and each participant was assessed by
      4 health care professionals. The health care professionals were asked to record
      whether observed signs and symptoms were potentially consistent with a diagnosis
      of RA. The health care professionals understood the study objective to be their
      agreement on GALS findings among one another and were unaware that one-half of
      the participants had RA. Sensitivity and specificity were calculated to determine
      the ability of the GALS examination to screen for RA using the rheumatologist as
      the standard for comparison. RESULTS: Sensitivity and specificity values varied
      from 60-100% and 70-82%, respectively, for the 3 family physicians, and 60-90%
      and 73-100%, respectively, for the 3 nurse practitioners. CONCLUSION: Following a
      very short training period, family physicians and nurse practitioners appeared to
      be able to use the GALS examination as a screening tool for RA signs and
      symptoms, particularly for identifying an individual with positive results who
      will benefit from further investigation or rheumatology referral.

PMID- 22623368
TI  - Histological and molecular evaluation of iron as degradable medical implant
      material in a murine animal model.
AB  - A small animal model was established to evaluate the potential of iron as a
      degradable implant material. After insertion into the tail of mice, the implants
      gradually degraded over a clinically relevant time period of several months.
      Histological analysis and gene expression data from whole-genome microarray
      analyses indicated a limited inflammatory reaction. No evidence of cellular
      responses to excess iron ions was detected, suggesting that the iron degradation
      products were metabolically inactive. Iron-rich compounds could be detected in
      the vicinity of the implant and in individual cells distant from the implantation
      site. These results demonstrate that the mouse model could be useful for the
      primary in vivo evaluation of novel implant materials and that iron degradation
      products can accumulate in diverse organs of the body.

PMID- 22623369
TI  - Targeting the E3 ubiquitin casitas B-lineage lymphoma decreases osteosarcoma cell
      growth and survival and reduces tumorigenesis.
AB  - Targeting receptor tyrosine kinase (RTK) degradation may be an interesting
      approach to reduce RTK cell signaling in cancer cells. Here we show that
      increasing E3 ubiquitin ligase casitas B-lineage lymphoma (c-Cbl) expression
      using lentiviral infection decreased osteosarcoma cell replication and survival
      and reduced cell migration and invasion in murine and human osteosarcoma cells.
      Conversely, c-Cbl inhibition using short hairpin RNA (shRNA) increased
      osteosarcoma cell growth and survival, as well as invasion and migration,
      indicating that c-Cbl plays a critical role as a bone tumor suppressor.
      Importantly, the anticancer effect of increasing c-Cbl expression in osteosarcoma
      cells was related mainly to the downregulation of epidermal growth factor
      receptor (EGFR) and platelet-derived growth factor receptor alpha (PDGFRalpha).
      In a murine bone tumor model, increasing c-Cbl expression also reduced RTK
      expression, resulting in decreased tumor cell proliferation and survival and
      reduced tumor growth. Interestingly, increasing c-Cbl also markedly reduced lung
      metastasis in mice. Tissue microarray analysis revealed that low c-Cbl protein
      expression is associated with elevated EGFR and PDGFRalpha protein levels in
      human osteosarcoma with poor outcome. This study shows that increasing c-Cbl
      expression reduces osteosarcoma cell growth, survival, and metastasis in part
      through downregulation of RTKs, which supports the potential therapeutic interest
      of targeting c-Cbl in malignant bone diseases involving increased RTK.

PMID- 22623370
TI  - Ytterbium-based bioprobes for near-infrared two-photon scanning laser microscopy
      imaging.

PMID- 22623371
TI  - Activated charcoal composite biomaterial promotes human embryonic stem cell
      differentiation toward neuronal lineage.
AB  - Transplantation of biomaterial scaffolds encasing human embryonic stem cells
      (hESCs) has been proposed as a clinical therapy for various neurological lesions
      and disorders. In light of recent developments, artificially synthesized carbon
      based biomaterials such as carbon nanotubes and graphene have demonstrated
      feasibility in supporting stem cell attachment and differentiation. However, the
      applicability is significantly hampered by evidence of nanotoxic effects on
      multiple cell types. Thus, an emergent drive for an innovative carbonaceous
      biomaterial calls for a safer platform with comparable advantageous
      characteristics. Here, we showed for the first time, a natural coal-based
      activated charcoal (AC) composite biosubstrate can support and promote neuronal
      differentiation in hESCs. The bio-friendly AC composite biomatrices resulted in
      more matured neuron-like cells. Both of axonal length and density were at least
      twice as long and abundant, respectively, when compared with control groups. A
      functional assay demonstrated that the derived neuron-like cells responded to
      depolarization-dependent synaptic recycling and may contain active synapses. In
      addition, the AC composite substrate can serve to concentrate growth factors and
      cell adhesion proteins, further encouraging attachment and hESC differentiation.
      Moreover, the AC composite biomaterial can potentially be economically
      manufactured as implantable three-dimensional bioscaffolds, facilitating the
      regeneration of damaged neural and other tissues.

PMID- 22623372
TI  - Clarification of the identity of the mammalian fifth pharyngeal arch artery.
AB  - The remodeling of the pharyngeal arch arteries is a complex process that occurs
      across vertebrates, although the specific number of arteries varies across
      species, with six in fish, but only five in birds and mammals, although they are
      numbered one through four, and six. The existence of a fifth arch artery in
      mammals has been debated for more than a century. Although some have doubted, and
      continue to doubt, its existence, several cardiovascular malformations can be
      explained only on the basis of its presence. We have analyzed the developing
      pharyngeal arch arteries in mouse and human embryos, using high-resolution
      episcopic microscopy. We have then created three-dimensional models, allowing us
      to identify any structures that would satisfy the descriptions of fifth arch
      arteries. This detailed examination revealed collateral channels connecting the
      fourth and sixth pharyngeal arch arteries in approximately half of the mouse
      embryos examined. Such collateral channels were seen in only one human embryo of
      eight examined by high-resolution episcopic microscopy, although we had
      previously identified such collateral channels using wax plate reconstruction. An
      extra vessel, occupying a discrete component of the pharyngeal mesenchyme, and
      therefore resembling a true fifth pharyngeal arch artery, was observed in one
      Carnegie Stage 14 human embryo. The pharyngeal mesenchyme in the human,
      therefore, can contain a fifth arch, with a contained artery, albeit transiently.
      Persistence of this structure, and the observed collateral channels, provides
      mechanisms to explain the congenital cardiovascular malformations described as
      persistent fifth aortic arch, and double-barreled aorta.

PMID- 22623373
TI  - Chemical cross-linking, mass spectrometry, and in silico modeling of proteasomal
      20S core particles of the haloarchaeon Haloferax volcanii.
AB  - A fast and accurate method is reported to generate distance constraints between
      juxtaposited amino acids and to validate molecular models of halophilic protein
      complexes. Proteasomal 20S core particles (CPs) from the haloarchaeon Haloferax
      volcanii were used to investigate the quaternary structure of halophilic proteins
      based on their symmetrical, yet distinct subunit composition. Proteasomal CPs are
      cylindrical barrel-like structures of four-stacked homoheptameric rings of alpha-
      and beta-type subunits organized in alpha(7)beta(7) beta(7)alpha(7)
      stoichiometry. The CPs of H. volcanii are formed from a single type of beta
      subunit associated with alpha1 and/or alpha2 subunits. Tandem affinity
      chromatography and new genetic constructs were used to separately isolate
      alpha1(7)beta(7)beta(7)alpha1(7) and alpha2(7)beta(7)beta(7)alpha2(7) CPs from H.
      volcanii. Chemically cross-linked peptides of the H. volcanii CPs were analyzed
      by high-performance mass spectrometry and an open modification search strategy to
      first generate and then to interpret the resulting tandem mass spectrometric
      data. Distance constraints obtained by chemical cross-linking mass spectrometry,
      together with the available structural data of nonhalophilic CPs, facilitated the
      selection of accurate models of H. volcanii proteasomal CPs composed of alpha1-,
      alpha2-, and beta-homoheptameric rings from several different possible structures
      from Protein Data Bank.

PMID- 22623374
TI  - Gaucher disease paradigm: from ERAD to comorbidity.
AB  - Mutations in the GBA gene, encoding the lysosomal acid beta-glucocerebrosidase
      (GCase), lead to deficient activity of the enzyme in the lysosomes, to
      glucosylceramide accumulation and to development of Gaucher disease (GD). More
      than 280 mutations in the GBA gene have been directly associated with GD. Mutant
      GCase variants present variable levels of endoplasmic reticulum (ER) retention,
      due to their inability to correctly fold, and undergo ER-associated degradation
      (ERAD) in the proteasomes. The degree of ER retention and proteasomal degradation
      is one of the factors that determine GD severity. In the present review, we
      discuss ERAD of mutant GCase variants and its possible consequences in GD
      patients and in carriers of GD mutations.

PMID- 22623375
TI  - Predicting protein dynamic binding capacity from batch adsorption tests.
AB  - The dynamic binding capacity (DBC) and its dependence on residence time influence
      the design and productivity of adsorption columns used in protein capture
      applications. This paper offers a very simple approach to predict the DBC of an
      adsorption column based on a measurement of the equilibrium binding capacity
      (EBC) and of the time needed to achieve one-half of the EBC in a batch adsorption
      test. The approach is based on a mass transfer kinetics model that assumes pore
      diffusion with a rectangular isotherm; however, the same approach is also shown
      to work for other systems where solute transport inside the particle occurs
      through other transport mechanisms.

PMID- 22623377
TI  - PepDistiller: A quality control tool to improve the sensitivity and accuracy of
      peptide identifications in shotgun proteomics.
AB  - In this study, we presented a quality control tool named PepDistiller to
      facilitate the validation of MASCOT search results. By including the number of
      tryptic termini, and integrating a refined false discovery rate (FDR) calculation
      method, we demonstrated the improved sensitivity of peptide identifications
      obtained from semitryptic search results. Based on the analysis of a complex data
      set, approximately 7% more peptide identifications were obtained using
      PepDistiller than using MASCOT Percolator. Moreover, the refined method generated
      lower FDR estimations than the percentage of incorrect target (PIT) fixed method
      applied in Percolator. Using a standard data set, we further demonstrated the
      increased accuracy of the refined FDR estimations relative to the PIT-fixed FDR
      estimations. PepDistiller is fast and convenient to use, and is freely available
      for academic access. The software can be downloaded from
      http://www.bprc.ac.cn/pepdistiller.

PMID- 22623376
TI  - Oncologic doses of zoledronic acid induce osteonecrosis of the jaw-like lesions
      in rice rats (Oryzomys palustris) with periodontitis.
AB  - Though osteonecrosis of the jaw (ONJ) is temporally-associated with the use of
      nitrogen-containing bisphosphonates (N-BPs), a cause-and-effect relationship has
      not yet been established. We hypothesize that ONJ is a two-stage process in
      which: (1) risk factors initiate pathologic processes in the oral cavity that
      lead to a supranormal rate of hard tissue necrosis; and (2) powerful
      antiresorptives reduce the rate of removal of necrotic bone sufficiently to allow
      its net accumulation in the jaw. To test this hypothesis, we used the rice rat
      model of periodontitis. At age 28 days, rats (n = 15/group) were placed on a high
      sucrose and casein diet to exacerbate the development of periodontitis. Animals
      were injected subcutaneously (SC) biweekly with vehicle or alendronate (ALN, 15
      ug/kg), or IV once monthly with vehicle, a low dose (LD) of zoledronic acid
      (ZOL), or a high dose (HD) of ZOL and sacrificed after 6, 12, 18, and 24 weeks.
      Mandibles and maxillae were analyzed to determine the effects on the: (1)
      progression of periodontitis; (2) integrity of alveolar bone; (3) status of bone
      resorption and formation; (4) vascularity; and (5) osteocyte viability. We found
      that only HD-ZOL induced ONJ-like lesions in mandibles of rice rats after 18 and
      24 weeks of treatment. These lesions were characterized by areas of exposed
      necrotic alveolar bone, osteolysis, a honeycomb-like appearance of the alveolar
      bone, presence of bacterial colonies, and periodontal tissue destruction. In
      addition, inhibition of bone formation, a paradoxical abolition of the
      antiresorptive effect of only HD-ZOL, increased osteocyte necrosis/apoptosis, and
      decreased blood vessel number were found after 18 and/or 24 weeks. Our study
      suggests that only HD-ZOL exacerbates the inflammatory response and periodontal
      tissue damage in rice rats, inducing bone lesions that resemble ONJ.

PMID- 22623378
TI  - Cancer and viruses: a double-edged sword.
AB  - Oncovirus, synonymously called a 'tumour virus', is a virus that can cause
      cancer. An oncolytic virus preferentially infects the host's cancer cells and
      lyses them, causing tumour destruction, and is thus referred to as a 'cancer
      killing virus'. With an estimated 11% of cancer-associated deaths caused by
      oncoviruses and the possibility that many cancers may be treated by using
      oncolytic viruses, the role of viruses in cancer may be viewed as a double-edged
      sword. A total of seven human cancer viruses have been identified as oncoviruses,
      having been associated with various cancers. Conversely, a large number of
      oncolytic viruses have shown great potential towards the treatment of certain
      types of cancer. Proteomics has now been applied towards understanding the
      complex interplay that exists between oncoviruses and the immune responses that
      serve to prevent oncoviral diseases. This review attempts to summarise the
      neoplastic potential of human tumour associated viruses and associated vaccine
      successes. The potential use of oncolytic viruses for the therapeutic
      intervention of cancer will also be discussed. Finally, this review will discuss
      the enormous potential of proteomics technology in the field of oncovirology.

PMID- 22623379
TI  - Up-regulation of p53 and mitochondrial signaling pathway in apoptosis by a
      combination of COX-2 inhibitor, Celecoxib and Dolastatin 15, a marine mollusk
      linear peptide in experimental colon carcinogenesis.
AB  - Programmed cell death, also known as apoptosis, is an active process occurring in
      eukaryotic cells and it depends on various sets of pro and anti-apoptotic
      proteins. Chemoprevention of colorectal cancer can be achieved by inducing
      apoptosis using synthetic compound, Celecoxib and natural peptide, Dolastatin 15
      in an effective manner. But the apoptotic signaling by these two drugs remain
      unclear. The present study was thus focused on the role of Bcl2 family of
      proteins and their interplay with p53 in rats during the chemoprevention by these
      two drugs. After treatment for 6 wk with 1, 2-dimethylhydrazine (DMH), animals
      showed a marked occurrence of multiple plaque lesions. However, a simultaneous
      treatment with Celecoxib and Dolastatin 15 decreases such number to a significant
      level. DMH treatment also decreases the number of apoptotic cells in the colonic
      enterocytes which were corrected to the normal level by Celecoxib and Dolastatin
      15. An increased expression of Bcl2 while other proteins like Bax, Apaf-1, cyt c,
      and caspases in the apoptotic pathway, and the tumor suppressor proteins, p53 and
      p21 get down-regulated after DMH treatment which were reverted back to normal
      with Celecoxib and Dolastatin 15. Also, cells having high mitochondrial membrane
      potential had been seen to increase to significant levels which were reduced
      after the administration of these anti-inflammatory drugs. In silico molecular
      docking studies also showed that Dolastatin 15 and Celecoxib may bind to the
      active site pocket of Bcl2 , thus revealing the direct target of Dolastatin 15
      and Celecoxib apart from binding to COX-2.

PMID- 22623380
TI  - In vivo evaluation of resorbable bone graft substitutes in mandibular sockets of
      the beagle.
AB  - Hydroxyapatite (Ca(10)(PO(4))(6)(OH)(2)), with its high biocompatibility and good
      bioaffinity, stimulates osteoconduction and is slowly replaced by the host bone
      after implantation. However, clinical use of HA as a bone substitute has proved
      problematic. It is difficult to prevent dispersion of the HA granules and to mold
      the granules into the desired shape. Calcium sulfate as a bone graft substitute
      is rapidly resorbed in vivo releasing calcium ions, but fails to provide a long
      term, three-dimensional framework to support osteoconduction. The setting
      properties of calcium sulfate, however, allow it to be applied in a slurry form,
      making it easier to handle and apply in different situations. This study examines
      the in vivo response of a (Hydroxyapatite, apatitic phase)/calcium sulfate
      dehydrate (CSD) composite using different ratios in the mandibular premolar
      sockets of the beagle. The HA (AP)/CSD composite materials prepared in ratios of
      30/70, 50/50, and 70/30 were implanted into the mandibular premolar sockets for 5
      and 10 weeks. The control socket was empty. The authors compared the radiographic
      properties and the changes in height and width of the mandibular premolar sockets
      in the beagle. The composite graft in the 30/70 ratio had the best ability to
      form new bones.

PMID- 22623381
TI  - Conserved and quickly evolving immunome genes have different evolutionary paths.
AB  - Genetic, transcript, and protein level variations have important functional and
      evolutionary consequences. We performed systematic data collection and analysis
      of copy-number variations, single-nucleotide polymorphisms, disease-causing
      variations, messenger RNA splicing variants, and protein posttranslational
      modifications for the genes and proteins essential for human immune system.
      Information about polymorphic and evolutionarily fixed genetic variations was
      used to group immunome genes to the most conserved and the most quickly changing
      ones under directed selection during the recent immunome evolution. Gene Ontology
      terms related to adaptive immunity are associated with gene groups subject to
      recent directing selection. In addition, several other characteristics of the
      immunome genes and proteins in these two categories have statistically
      significant differences. The presented findings question the usability of
      directed mouse genes as models for human diseases and conditions and shed light
      on the fine tuning of human immunity and its diverse functions.

PMID- 22623382
TI  - Obesity-related eating behaviors are associated with low physical activity and
      poor diet quality in Spain.
AB  - This study examined the association of obesity-related eating behaviors (OREB)
      with physical activity, sedentariness, and diet quality. Data were taken from a
      cross-sectional study in 10,791 persons representative of the Spanish population
      who were >=18 y of age in 2008-2010. The following self-reported information was
      collected on 12 OREB: not planning how much to eat before sitting down, not
      deciding the amount of food on the plate, skipping breakfast, eating
      precooked/canned food or snacks bought at vending machines or at fast-food
      restaurants, not choosing low-energy foods, not removing visible fat from meat or
      skin from chicken, eating while watching television or seated on a sofa or an
      armchair, and taking a short time for meals. Analyses were performed with linear
      or logistic regression, as appropriate, and adjusted for the main confounders. In
      comparison to participants with <=1 OREB, those with >=5 OREB performed less
      physical activity [beta: -2.61 (95% CI: -4.44, -0.78); P-trend < 0.001] and spent
      more time watching television [beta: 2.17 (95% CI: 1.39, 2.95); P-trend < 0.001];
      furthermore, they had greater total energy intake [beta: 160 (95% CI: 115, 210);
      P-trend < 0.001] and were less likely to follow a Mediterranean diet [OR: 0.55
      (95% CI: 0.41, 0.73); P-trend < 0.001]. In conclusion, the association between
      OREB and obesity is biologically plausible because OREB are associated with
      energy intake and poor accordance with the Mediterranean diet. Studies on the
      association between OREB and obesity should control for the confounding effect of
      physical activity and sedentariness.

PMID- 22623383
TI  - alpha-Lactalbumin and casein-glycomacropeptide do not affect iron absorption from
      formula in healthy term infants.
AB  - Iron absorption from infant formula is relatively low. alpha-Lactalbumin and
      casein-glycomacropeptide have been suggested to enhance mineral absorption. We
      therefore assessed the effect of alpha-lactalbumin and casein-glycomacropeptide
      on iron absorption from infant formula in healthy term infants. Thirty-one
      infants were randomly assigned to receive 1 of 3 formulas (4 mg iron/L, 13.1 g
      protein/L) from 4-8 wk to 6 mo of age: commercially available whey-predominant
      standard infant formula (standard formula), alpha-lactalbumin-enriched infant
      formula (alpha-LAC), or alpha-lactalbumin-enriched/casein-glycomacropeptide
      reduced infant formula (alpha-LAC/RGMP). Nine breast-fed infants served as a
      reference. At 5.5 mo of age, (58)Fe was administered to all infants in a meal.
      Blood samples were collected 14 d later for iron absorption and iron status
      indices. Iron deficiency was defined as depleted iron stores, iron-deficient
      erythropoiesis, or iron deficiency anemia. Iron absorption (mean +/- SD) was 10.3
      +/- 7.0% from standard formula, 8.6 +/- 3.8% from alpha-LAC, 9.2 +/- 6.5% from
      alpha-LAC/RGMP, and 12.9 +/- 6.5% from breast milk, with no difference between
      the formula groups (P = 0.79) or all groups (P = 0.44). In the formula-fed
      infants only, iron absorption was negatively correlated with serum ferritin (r = 
      0.49; P = 0.005) and was higher (P = 0.023) in iron-deficient infants (16.4 +/-
      12.4%) compared with those with adequate iron status (8.6 +/- 4.4%). Our findings
      indicate that alpha-lactalbumin and casein-glycomacropeptide do not affect iron
      absorption from infant formula in infants. Low serum ferritin concentrations are
      correlated with increased iron absorption from infant formula.

PMID- 22623384
TI  - Plasma pyridoxal-5-phosphate is inversely associated with systemic markers of
      inflammation in a population of U.S. adults.
AB  - Low vitamin B-6 status, based on plasma concentrations of pyridoxal-5-phosphate
      (PLP), has been identified in inflammatory diseases, including cardiovascular
      disease, rheumatoid arthritis, inflammatory bowel disease, and diabetes. Our
      objective was to examine the association between plasma PLP and multiple markers
      of inflammation in a community-based cohort [n = 2229 participants (55% women,
      mean age 61 +/- 9 y)]. We created an overall inflammation score (IS) as the sum
      of standardized values of 13 individual inflammatory markers. Multivariable
      adjusted regression analysis was used to assess the associations between the IS
      and plasma PLP. Geometric mean plasma PLP concentrations were lower in the
      highest tertile category of IS relative to the lowest (61 vs. 80 nmol/L; P-trend
      < 0.0001). Similarly, the prevalence of PLP insufficiency was significantly
      higher for participants in the highest compared with the lowest tertiles for IS
      categories. These relationships persisted after accounting for vitamin B-6
      intake. Also, there were significant inverse relationships between plasma PLP and
      4 IS based on functionally related markers, including acute phase reactants,
      cytokines, adhesion molecules, and oxidative stress. In addition, secondary
      analyses revealed that many of the individual inflammatory markers were inversely
      associated with plasma PLP after adjusting for plasma C-reactive protein
      concentration. This study, in combination with past findings, further supports
      our hypothesis that inflammation is associated with a functional deficiency of
      vitamin B-6. We discuss 2 possible roles for PLP in the inflammatory process,
      including tryptophan metabolism and serine hydroxymethyltransferase activity.

PMID- 22623385
TI  - Ergocalciferol from mushrooms or supplements consumed with a standard meal
      increases 25-hydroxyergocalciferol but decreases 25-hydroxycholecalciferol in the
      serum of healthy adults.
AB  - Few foods contain ergocalciferol or cholecalciferol. Treatment of mushrooms with
      UV light increases ergocalciferol content and could provide a dietary source of
      vitamin D. We evaluated the impact of consuming UV-treated white button mushrooms
      (Agaricus bisporus) on the vitamin D status of healthy adults. Thirty-eight
      volunteers were randomized to 4 treatments consumed with a standard meal for 6
      wk: the control (C) group received untreated mushrooms providing 0.85 MUg/d
      ergocalciferol (n = 10); groups M1 and M2 received UV-treated mushrooms providing
      8.8 (n = 10) and 17.1 MUg/d (n = 9), respectively; and the supplement (S) group
      received purified ergocalciferol plus untreated mushrooms, providing a total of
      28.2 MUg/d (n = 9). Serum total 25-hydroxyvitamin D [25(OH)D] and 25
      hydroxyergocalciferol [25(OH)D2] were 83 +/- 38 and 2.4 +/- 2.0 nmol/L,
      respectively, at baseline (mean +/- SD). At wk 6, 25(OH)D2 had increased and was
      higher in all treatment groups than in the C group, whereas 25
      hydroxycholecalciferol [25(OH)D3] had decreased and was lower in the M2 and S
      groups than in the C group. Increases in 25(OH)D2 for groups C, M1, M2, and S
      were 1.2 +/- 5.2, 13.8 +/- 7.3, 12.7 +/- 3.7, and 32.8 +/- 3.3 nmol/L and
      decreases in 25(OH)D3 were -3.9 +/- 16.3, -10.4 +/- 6.4, -20.6 +/- 14.6, and 
      29.5 +/- 15.9 nmol/L, respectively. Concentrations did not change in group C. In
      summary, ergocalciferol was absorbed and metabolized to 25(OH)D2 but did not
      affect vitamin D status, because 25(OH)D3 decreased proportionally.

PMID- 22623387
TI  - Dietary long-chain PUFA enhance acute repair of ischemia-injured intestine of
      suckling pigs.
AB  - Infant formula companies have been fortifying formulas with long-chain PUFA for
      10 y. Long-chain PUFA are precursors of prostanoids, which stimulate recovery of
      intestinal barrier function. Supplementation of milk with PUFA increases the
      content of arachidonic acid (ARA) in enterocyte membranes; however, the effect of
      this enrichment on intestinal repair is not known. The objective of these
      experiments was to investigate the effect of supplemental ARA on intestinal
      barrier repair in ischemia-injured porcine ileum. One-day-old pigs (n = 24) were
      fed a milk-based formula for 10 d. Diets contained no PUFA (0% ARA), 0.5% ARA, 5%
      ARA, or 5% EPA of total fatty acids. Following dietary enrichment, ilea were
      subjected to in vivo ischemic injury by clamping the local mesenteric blood
      supply for 45 min. Following the ischemic period, control (nonischemic) and
      ischemic loops were mounted on Ussing chambers. Transepithelial electrical
      resistance (TER) was measured over a 240-min recovery period. Ischemia-injured
      ileum from piglets fed 5% ARA (61.0 +/- 14%) exhibited enhanced recovery compared
      with 0% ARA (16 +/- 14) and 0.5% ARA (22.1 +/- 14)-fed pigs. Additionally,
      ischemia-injured ileum from 5% EPA (51.3 +/- 14)-fed pigs had enhanced recovery
      compared with 0% ARA-fed pigs (P < 0.05). The enhanced TER recovery response
      observed with ischemia-injured 5% ARA supplementation was supported by a
      significant reduction in mucosal-to-serosal flux of (3)H-mannitol and (14)C
      inulin compared with all other ischemia-injured dietary groups (P < 0.05). A
      histological evaluation of ischemic ilea from piglets fed the 5% ARA showed
      reduced histological lesions after ischemia compared with the other dietary
      groups (P < 0.05). These data demonstrate that feeding elevated levels of long
      chain PUFA enhances acute recovery of ischemia-injured porcine ileum.

PMID- 22623386
TI  - Changes in erythrocyte membrane trans and marine fatty acids between 1999 and
      2006 in older Americans.
AB  - Over the last several years, national programs to lower the content of
      industrially produced (IP) C18:1 and C18:2 trans fatty acids in foods have been
      implemented, but whether this has resulted in lower blood trans fatty acid levels
      is unknown. Likewise, an increased perception of the health benefits of fish oils
      rich in EPA and DHA may have resulted in an increase in consumption and blood
      levels of these fatty acids. To explore these issues, we analyzed the changes in
      RBC fatty acid composition between the 7th (1998-2001) and 8th (2005-2007)
      examination cycles in a random sample of the Framingham Offspring cohort. This
      was a retrospective cohort study of 291 participants from whom blood was drawn at
      both examinations and for whom complete covariate data were available. Overall,
      the proportion of trans fatty acids in RBC changed by -23% (95% CI: -26 to -21%).
      RBC EPA+DHA proportions increased by 41% (95% CI: 31 to 52%) in 38 individuals
      who were taking fish oil supplements at examination 8, but in 253 participants
      not taking fish oil, the proportion of RBC EPA+DHA did not change. In conclusion,
      in a random subsample of Framingham Offspring participants with serial
      observations over 6.7 y, the proportion of trans fatty acids in RBC decreased.
      Those of EPA+DHA increased in people taking fish oil supplements. These changes
      could potentially translate into a lower risk for cardiovascular disease.

PMID- 22623388
TI  - Commentary on prebiotic utility in colitis: will inflammasomics hold the key?

PMID- 22623389
TI  - Plasma inflammatory and vascular homeostasis biomarkers increase during human
      pregnancy but are not affected by oily fish intake.
AB  - The Salmon in Pregnancy Study investigated whether the increased consumption of
      (n-3) long-chain PUFA (LC-PUFA) from farmed Atlantic salmon affects immune
      function during pregnancy and atopic disease in neonates compared with a habitual
      diet low in oily fish. In this context, because the ingestion of (n-3) LC-PUFA
      may lower the concentrations of inflammatory biomarkers, we investigated whether
      the consumption of oily fish affects the levels of inflammatory cytokines and
      vascular adhesion factors during pregnancy. Pregnant women (n = 123) were
      randomly assigned to continue their habitual diet (control group, n = 61), which
      was low in oily fish, or to consume two 150-g salmon portions/wk (salmon group, n
      = 62; providing 3.45 g EPA plus DHA) from 20 wk of gestation until delivery.
      Plasma inflammatory cytokines and vascular adhesion factors were measured in
      maternal plasma samples. Inflammatory biomarkers, including IL-8, hepatocyte
      growth factor, and monocyte chemotactic protein, increased over the course of
      pregnancy (P < 0.001), whereas plasma matrix metalloproteinase 9, IL-6, TNFalpha,
      and nerve growth factor concentrations were not affected. Vascular homeostasis
      biomarkers soluble E-selectin, soluble vascular adhesion molecule-1, soluble
      intercellular adhesion molecule (sICAM)-1, and total plasminogen activator
      inhibitor-1 increased as pregnancy progressed (P < 0.001). The plasma sICAM-1
      concentration was greater in the control group than in the salmon group at wk 20
      (baseline) and 38 (P = 0.007) but there was no group x time interaction, and when
      baseline concentration was used as a covariate, the groups did not differ (P =
      0.69). The remaining biomarkers analyzed were similar in both groups. Therefore,
      although some inflammatory and vascular homeostasis biomarkers change during
      pregnancy, they are not affected by the increased intake of farmed salmon.

PMID- 22623390
TI  - Hippuric acid in 24-hour urine collections is a potential biomarker for fruit and
      vegetable consumption in healthy children and adolescents.
AB  - An objective noninvasive biomarker for fruit and vegetable (FV) consumption would
      help to more reliably characterize the relationship between FV intake and health
      status in observational studies. Because increases in urinary hippuric acid (HA)
      were observed after consumption of several FV varieties, we aimed to investigate
      whether 24-h urinary HA may represent a potential biomarker for FV consumption in
      children and adolescents. The association of FV and juice (FVJ) intake calculated
      from 3-d weighed dietary records with 24-h urinary HA excretion was analyzed in
      240 healthy children and adolescents and compared with associations of the
      established biomarkers urinary nitrogen (uN) and urinary potassium (uK) with
      protein and potassium intake, respectively. Spearman correlation coefficients (r)
      and cross-classifications were calculated for all diet-biomarker associations.
      Potential confounders for the HA-FVJ association were examined in linear
      regression models. In children, correlations of HA with FVJ (r = 0.62), uN with
      protein (r = 0.64), and potassium intake with uK (r = 0.65) were comparable. In
      adolescents, the HA-FVJ association was weaker (r = 0.41) compared with the
      biomarkers uN (r = 0.60) and uK (r = 0.58) (all P < 0.0001). Cross-classification
      into the same/adjacent quartile by dietary and urinary data were >85% for all
      analyzed comparisons except for a 75% classification agreement between HA and FVJ
      in adolescents. Unadjusted and adjusted linear regression models indicated
      significant (P < 0.0001) HA-FVJ associations in both age groups. FVJ explained
      more of the variability in HA excretion in children (R(2) = 0.38) than in
      adolescents (R(2) = 0.22). Our findings in children showing HA-FVJ associations
      comparable to those for well-established biomarkers with their respective dietary
      intakes suggest that HA may represent a useful biomarker for FVJ.

PMID- 22623391
TI  - Bitter melon seed oil-attenuated body fat accumulation in diet-induced obese mice
      is associated with cAMP-dependent protein kinase activation and cell death in
      white adipose tissue.
AB  - The aim of this study was to investigate the antiadiposity effect of bitter melon
      seed oil (BMSO), which is rich in the cis-9, trans-11, trans-13 isomer of
      conjugated linolenic acid. In Expt. 1, C57BL/6J mice were fed a butter-based,
      high-fat diet [HB; 29% butter + 1% soybean oil (SBO)] for 10 wk to induce
      obesity. They then continued to receive that diet or were switched to an SBO
      based, high-fat diet alone (HS; 30% SBO) or containing bitter melon seed oil
      (BMSO) (HBM; 15% SBO + 15% BMSO) for 5 wk. The body fat percentage was
      significantly lower in mice fed the HBM diet (21%), but not the HS diet, compared
      with mice fed the HB diet. In Expt. 2, mice were fed an SBO-based, high-fat diet
      containing 0 (HS), 5 (LBM), 10 (MBM), or 15% (HBM) BMSO for 10 wk. In the LBM,
      MBM, and HBM groups, the body fat percentage was significantly lower by 32, 35,
      and 65%, respectively, compared with the HS control. The reduction in the HBM
      group was significantly greater than that in the LBM or MBM group. BMSO
      administration increased phosphorylation of acetyl-CoA carboxylase, cAMP
      activated protein kinase (PKA), and signal transducer and activator of
      transcription 3 in the white adipose tissue (WAT), suggesting that PKA and leptin
      signaling might be involved in the BMSO-mediated reduction in lipogenesis and
      increase in thermogenesis and lipolysis. However, compared with the HS control,
      the HBM group had a significantly higher TNFalpha concentration in the WAT
      accompanied by TUNEL-positive nuclei. We conclude that BMSO is effective in
      attenuating body fat accumulation through mechanisms associated with PKA
      activation and programmed cell death in the WAT, but safety concerns need to be
      carefully addressed.

PMID- 22623392
TI  - Consumption of a high monounsaturated fat diet reduces oxidative phosphorylation
      gene expression in peripheral blood mononuclear cells of abdominally overweight
      men and women.
AB  - The Mediterranean (MED) diet is often considered health-promoting due to its high
      content of MUFA and polyphenols. These bioactive compounds can affect gene
      expression and accordingly may regulate pathways and proteins related to
      cardiovascular disease prevention. This study aimed to identify the effects of a
      MED-type diet, and the replacement of SFA with MUFA in a Western-type diet, on
      peripheral blood mononuclear cell (PBMC) gene expression and plasma proteins.
      Abdominally overweight men and women (waist: women >=80 cm, men >=94 cm) were
      allocated to an 8-wk, completely controlled SFA diet (19% daily energy as SFA), a
      MUFA diet (20% daily energy MUFA), or a MED diet (21% daily energy MUFA).
      Concentrations of 124 plasma proteins and PBMC whole-genome transcriptional
      profiles were assessed. Consumption of the MUFA and MED diets, compared with the
      SFA diet, decreased the expression of oxidative phosphorylation (OXPHOS) genes,
      plasma connective tissue growth factor, and apoB concentrations. Compared with
      the MED and SFA diets, the MUFA diet changed the expression of genes involved in
      B-cell receptor signaling and endocytosis signaling. Participants who consumed
      the MED diet had lower concentrations of proinflammatory proteins at 8 wk
      compared with baseline. We hypothesize that replacement of SFA with MUFA may
      improve health, thereby reducing metabolic stress and OXPHOS activity in PBMC.
      The MED diet may have additional antiatherogenic effects by lowering
      proinflammatory plasma proteins.

PMID- 22623393
TI  - Wasting is associated with stunting in early childhood.
AB  - The longitudinal relationship between stunting and wasting in children is poorly
      characterized. Instances of wasting or poor weight gain may precede linear growth
      retardation. We analyzed longitudinal anthropometric data for 1599 children from
      8 cohort studies to determine the effect of wasting [weight-for-length Z-score
      (WLZ) < -2] and variability in WLZ in the first 17 mo on length-for-age Z-score
      (LAZ) at 18-24 mo of age. In addition, we considered the effects of change in WLZ
      during the previous 6-mo period on length at 18 and 24 mo. Wasting at 6-11 or 12
      17 mo was associated with decreased LAZ; however, children who experienced
      wasting only at 0-5 mo did not suffer any long-term growth deficits compared with
      children with no wasting during any period. Children with greater WLZ variability
      (>=0.5 SD) in the first 17 mo of life were shorter [LAZ = -0.51 SD (95% CI: 
      0.67, -0.36 SD)] at 18-24 mo of age than children with WLZ variability <0.5.
      Change in WLZ in the previous 6-mo period was directly associated with greater
      attained length at 18 mo [0.33 cm (95% CI: 0.11, 0.54 cm)] and 24 mo [0.72 cm
      (95% CI: 0.52, 0.92 cm)]. Children with wasting, highly variable WLZ, or negative
      changes in WLZ are at a higher risk for linear growth retardation, although
      instances of wasting may not be the primary cause of stunting in developing
      countries.

PMID- 22623394
TI  - A Period 2 genetic variant interacts with plasma SFA to modify plasma lipid
      concentrations in adults with metabolic syndrome.
AB  - Genetic variants of Period 2 (PER2), a circadian clock gene, have been linked to
      metabolic syndrome (MetS). However, it is still unknown whether these genetic
      variants interact with the various types of plasma fatty acids. This study
      investigated whether common single nucleotide polymorphisms (SNPs) in the PER2
      locus (rs934945 and rs2304672) interact with various classes of plasma fatty
      acids to modulate plasma lipid metabolism in 381 participants with MetS in the
      European LIPGENE study. Interestingly, the rs2304672 SNP interacted with plasma
      total SFA concentrations to affect fasting plasma TG, TG-rich lipoprotein (TRL
      TG), total cholesterol, apoC-II, apoB, and apoB-48 concentrations (P-interaction
      < 0.001-0.046). Carriers of the minor allele (GC+GG) with the highest SFA
      concentration (>median) had a higher plasma TG concentration (P = 0.001) and
      higher TRL-TG (P < 0.001) than the CC genotype. In addition, participants
      carrying the minor G allele for rs2304672 SNP and with a higher SFA concentration
      (>median) had higher plasma concentrations of apo C-II (P < 0.001), apo C-III (P
      = 0.009), and apoB-48 (P = 0.028) compared with the homozygotes for the major
      allele (CC). In summary, the rs2304672 polymorphism in the PER2 gene locus may
      influence lipid metabolism by interacting with the plasma total SFA concentration
      in participants with MetS. The understanding of these gene-nutrient interactions
      could help to provide a better knowledge of the pathogenesis in MetS.

PMID- 22623395
TI  - Galacto-oligosaccharides have prebiotic activity in a dynamic in vitro colon
      model using a (13)C-labeling technique.
AB  - Galacto-oligosaccharides (GOS) are considered to be prebiotic, although the
      contribution of specific members of the microbiota to GOS fermentation and the
      exact microbial metabolites that are produced upon GOS fermentation are largely
      unknown. We aimed to determine this using uniformly (13)C-labeled GOS. The normal
      (control) medium and unlabeled or (13)C-labeled GOS was added to a dynamic,
      validated, in vitro model of the large-intestine containing an adult-type
      microbiota. Liquid-chromatography MS was used to measure the incorporation of
      (13)C label into metabolites. 16S-rRNA stable isotope probing coupled to a
      phylogenetic micro-array was used to determine label incorporation in microbial
      biomass. The primary members within the complex microbiota that were directly
      involved in GOS fermentation were shown to be Bifidobacterium longum, B. bifidum,
      B. catenulatum, Lactobacillus gasseri, and L. salivarius, in line with the
      prebiotic effect of GOS, although some other species incorporated (13)C label
      also. GOS fermentation led to an increase in acetate (+49%) and lactate (+23%)
      compared with the control. Total organic acid production was 8.50 and 7.52 mmol/g
      of carbohydrate fed for the GOS and control experiments, respectively. At the
      same time, the cumulative production of putrefactive metabolites (branched-chain
      fatty acids and ammonia) was reduced by 55%. Cross-feeding of metabolites from
      primary GOS fermenters to other members of the microbiota was observed. Our
      findings support a prebiotic role for GOS and its potential to act as a synbiotic
      in combination with certain probiotic strains.

PMID- 22623396
TI  - Fortified malted milk drinks containing low-dose ergocalciferol and
      cholecalciferol do not differ in their capacity to raise serum 25-hydroxyvitamin
      D concentrations in healthy men and women not exposed to UV-B.
AB  - Uncertainty remains regarding the efficacy of low intakes of ergocalciferol
      (vitamin D2 or D2) and cholecalciferol (vitamin D3 or D3) provided in food to
      increase serum 25-hydroxy-vitamin D (25-OH-D) metabolite concentrations when UV-B
      exposure is low. We recruited 40 healthy men and women into a double-blind,
      parallel design, randomized controlled trial. Participants received placebo or 1
      of 4 experimental treatments (D2 or D3 at 5 or 10 MUg/d) supplied as a malted
      milk drink for 4 wk during a period of minimal UV-B exposure in the UK. The
      primary outcome was a change in serum 25-OH-D2 and 25-OH-D3 concentrations
      measured by ultra-performance liquid chromatography tandem MS. The secondary
      outcomes were changes in concentrations of plasma parathyroid hormone and serum
      calcium (Ca(2+)). Baseline concentrations (geometric mean +/- SD) of 25-OH-D2, 25
      OH-D3, and total 25-OH-D were 3 +/- 4, 32 +/- 22, and 37 +/- 22 nmol/L,
      respectively. Both D2- and D3-fortified drinks resulted in dose-dependent
      increases (P < 0.001) in their respective 25-OH metabolites that did not
      significantly differ in size. Increments from baseline compared with the placebo
      group following 5 and 10 MUg/d of D2 were (mean +/- SEM) 9.4 +/- 2.5 and 17.8 +/-
      2.4 nmol/L for 25-OH-D2 and following 5 and 10 MUg/d of D3 were 15.1 +/- 4.7 and
      22.9 +/- 4.6 nmol/L for 25-OH-D3, respectively. There was no difference between
      D2 and D3 groups in the incremental AUC of their respective metabolites. These
      findings suggest that D2 and D3 are equipotent in increasing 25-OH-D in healthy
      men and women with negligible UV-B exposure.

PMID- 22623397
TI  - Children live, feel, and respond to experiences of food insecurity that
      compromise their development and weight status in peri-urban Venezuela.
AB  - Children's experiences of food insecurity (FI) may be conceptually distinct and
      different from those of adults. Previous study of children's experiences of FI
      has relied primarily on their parents' perspective. This study explored,
      described, and conceptualized experiences of FI in children attending 5 public
      schools in peri-urban areas of the Miranda State, Venezuela, South America using
      a naturalistic approach. Children aged 10-17 y were studied through focus groups
      (n = 42) and individual interviews (n = 13). Interviews were recorded,
      transcribed, and analyzed using grounded theory. Children were cognitively aware
      of FI, worry in their parents, and causes both external and internal to their
      households. Children were also emotionally aware of FI, with feelings of concern,
      anguish, and sadness, and manifestations such as crying. Children reported being
      physically hungry, experiencing reduced quantity and quality of food intake,
      having smaller meals, and recognizing thinness and fainting as consequences.
      Children's responses to FI included reduction of quality and quantity of food,
      child labor, sacrifice in food consumption, food from waste, support from
      extended family members, and strategies for purchasing, acquiring, preparing, and
      cooking food. Children were not always protected, especially when the head of the
      family was unemployed, had drug-alcohol problems, or was extremely poor.
      Protection could come from parents to children and from older children to parents
      and younger children. Children should have certain access to food that is
      dignified, timely, efficient, and adequate in harmonious social conditions to
      prevent and resolve situations that compromise their physical, cognitive, and
      socio-emotional well-being.

PMID- 22623398
TI  - Structural characterization and computer-aided optimization of a small-molecule
      inhibitor of the Arp2/3 complex, a key regulator of the actin cytoskeleton.
AB  - CK-666 (1) is a recently discovered small-molecule inhibitor of the actin-related
      protein 2/3 (Arp2/3) complex, a key actin cytoskeleton regulator with roles in
      bacterial pathogenesis and cancer cell motility. Although 1 is commercially
      available, the crystal structure of Arp2/3 complex with 1 bound has not been
      reported, making its mechanism of action uncertain. Furthermore, its relatively
      low potency increases its potential for off-target effects in vivo, complicating
      interpretation of its influence in cell biological studies and precluding its
      clinical use. Herein we report the crystal structure of 1 bound to Arp2/3
      complex, which reveals that 1 binds between the Arp2 and Arp3 subunits to
      stabilize the inactive conformation of the complex. Based on the crystal
      structure, we used computational docking and free-energy perturbation
      calculations of monosubstituted derivatives of 1 to guide optimization efforts.
      Biochemical assays of ten newly synthesized compounds led to the identification
      of compound 2, which exhibits a threefold increase in inhibitory activity in
      vitro relative to 1. In addition, our computational analyses unveiled a surface
      groove at the interface of the Arp2 and Arp3 subunits that can be exploited for
      additional structure-based optimization.

PMID- 22623399
TI  - Sequence determinants of protein folding rates: positive correlation between
      contact energy and contact range indicates selection for fast folding.
AB  - In comparison with intense investigation of the structural determinants of
      protein folding rates, the sequence features favoring fast folding have received
      little attention. Here, we investigate this subject using simple models of
      protein folding and a statistical analysis of the Protein Data Bank (PDB). The
      mean-field model by Plotkin and coworkers predicts that the folding rate is
      accelerated by stronger-than-average interactions at short distance along the
      sequence. We confirmed this prediction using the Finkelstein model of protein
      folding, which accounts for realistic features of polymer entropy. We then tested
      this prediction on the PDB. We found that native interactions are strongest at
      contact range l = 8. However, since short range contacts tend to be exposed and
      they are frequently formed in misfolded structures, selection for folding
      stability tends to make them less attractive, that is, stability and kinetics may
      have contrasting requirements. Using a recently proposed model, we predicted the
      relationship between contact range and contact energy based on buriedness and
      contact frequency. Deviations from this prediction induce a positive correlation
      between contact range and contact energy, that is, short range contacts are
      stronger than expected, for 2/3 of the proteins. This correlation increases with
      the absolute contact order (ACO), as expected if proteins that tend to fold
      slowly due to large ACO are subject to stronger selection for sequence features
      favoring fast folding. Our results suggest that the selective pressure for fast
      folding is detectable only for one third of the proteins in the PDB, in
      particular those with large contact order.

PMID- 22623400
TI  - Proteomic analysis of Taenia solium metacestode excretion-secretion proteins.
AB  - The metacestode larval stage of Taenia solium is the causal agent of a zoonotic
      disease called cysticercosis. The disease has an important impact on pork trade
      (due to porcine cysticercosis) and public health (due to human
      neurocysticercosis). In order to improve the current diagnostic tools and to get
      a better understanding of the interaction between T. solium metacestodes and
      their host, there is a need for more information about the proteins that are
      released by the parasite. In this study, we used protein sequences from different
      helminths, 1DE, reversed-phase LC, and MS/MS to analyze the excretion-secretion
      proteins produced by T. solium metacestodes from infected pigs. This is the first
      report of the T. solium metacestode excretion-secretion proteome. We report 76
      proteins including 27 already described T. solium proteins, 17 host proteins and
      32 proteins likely to be of T. solium origin, but identified using sequences from
      other helminths.

PMID- 22623401
TI  - Cerebrospinal fluid top-down proteomics evidenced the potential biomarker role of
      LVV- and VV-hemorphin-7 in posterior cranial fossa pediatric brain tumors.
AB  - Posterior cranial fossa is the most frequent location of pediatric brain tumors.
      Its diagnosis is currently performed by postsurgery histopathology and the
      identification of biomarkers in cerebrospinal fluid (CSF) could provide a less
      invasive tool. Patient CSF was collected during surgery before the tumor removal
      (PRE-CSF) and 6 days after the resection (POST-CSF) and analyzed by top down LC
      MS proteomics for comparison. The PRE-CSFs generally exhibited a less complex LC
      MS profile than the relative POST-CSFs suggesting a suppressive role of the tumor
      toward proteins and peptides production or release. Particularly, a panel of
      peptides, identified as alpha- and beta-hemoglobin chains fragments, were
      generally absent in the PRE-CSF and present in the POST ones independently from
      contaminant blood hemoglobin. Among them, the LVV- and VV-hemorphin-7 showed the
      most repeatable trend and with a few remarkable exceptions: their unusual absence
      in POST surgery CSF was in fact interestingly correlated to the presence of tumor
      in the patient despite surgery due to metastases or to subtotal resection. These
      results ascribed a relevant biological role to LVV- and VV-h7 peptides in the
      disease and a strong potential as biomarkers. Their analysis in POST surgery CSF
      could be used to predict patient prognosis.

PMID- 22623402
TI  - Cognitive skills and academic achievement of deaf children with cochlear
      implants.
AB  - OBJECTIVE: To compare cognitive performance between children with cochlear
      implants (CI) and normal-hearing peers; provide information about correlations
      between cognitive performance, basic academic achievement, and
      medical/audiological and social background variables; and assess the predictor
      quality of these variables for cognition. STUDY DESIGN: Cross-sectional study
      with comparison group, diagnostic test assessment. SETTING: Data were collected
      in the authors' clinic (children with CI) and in Austrian schools (normal-hearing
      children). SUBJECTS AND METHODS: Forty children with CI (of the initial 65
      children eligible for this study), aged 7 to 11 years, and 40 normal-hearing
      children, matched by age and sex, were tested with (a) the Culture Fair
      Intelligence Test (CFIT); (b) the Number Sequences subtest of the Heidelberger
      Rechentest 1-4 (HRT); (c) Comprehension, (d) Coding, (e) Digit Span, and (f)
      Vocabulary subtests of HAWIK III (German WISC III); (g) the Corsi Block Tapping
      Test; (h) the Arithmetic Operations subtests of the HRT; and (i) Salzburger Lese
      Screening (SLS, reading). In addition, medical, audiological, social, and
      educational data from children with CI were collected. RESULTS: The children with
      CI equaled normal-hearing children in (a), (d), (e), (g), (h), and (i) and
      performed significantly worse in (b), (c) and (f). Background variables correlate
      significantly with cognitive skills and academic achievement.
      Medical/audiological variables explain 44.3% of the variance in CFT1 (CFIT,
      younger children). Social variables explain 55% of CFT1 and 24.5% of the Corsi
      test. CONCLUSIONS: This study augments the knowledge about cognitive skills and
      academic skills of children with CI. Cognitive performance is dependent on the
      early feasibility to hear and the social/educational background of the family.

PMID- 22623403
TI  - Longitudinal tracheoesophageal puncture size stability.
AB  - OBJECTIVE: The purpose of this study is to investigate prosthesis size stability
      over time and determine which factors influence need for change in size. STUDY
      DESIGN: Retrospective chart review. SETTING: Teaching hospital. SUBJECTS AND
      METHODS: Retrospective chart review was performed on all individuals who had
      previously undergone total laryngectomy and tracheoesophageal puncture and had a
      minimum of 3 years of consistent and consecutive follow-up data after their
      prosthesis was initially placed. Data reviewed included demographic variables of
      age at time of tracheoesophageal puncture, ethnicity, and sex. RESULTS: Fifty
      patients were identified who met criteria for study inclusion with a mean age of
      64.7 years (range, 43-86 years) with 41 (82%) men and 9 (18%) women. Surgical
      management was equally divided between those who underwent total laryngectomy (n
      = 25) as primary treatment vs those who had salvage laryngectomy (n = 25) for
      persistent or recurrent disease. Prosthesis size was stable, with no change in
      diameter or length, in only 5 (10%) patients and unstable in 45 (90%), as they
      were changed at least once. The only factor that demonstrated statistical
      significance was sex (Fisher exact test = 0.035), with women being more likely to
      have a stable prosthesis size over time. CONCLUSIONS: The results of this study
      demonstrate that 90% of patients who underwent total laryngectomy and
      tracheoesophageal puncture required a change in their prosthesis size beyond the
      first 3 months of expected healing. These results support the need for continual
      reassessment of the fistula tract when changing the prosthesis to ensure
      appropriate fit.

PMID- 22623404
TI  - Development of a broad spectrum polymer-released antimicrobial coating for the
      prevention of resistant strain bacterial infections.
AB  - More than 400,000 primary hip and knee replacement surgeries are performed each
      year in the United States. From these procedures, approximately 0.5-3% will
      become infected and when considering revision surgeries, this rate has been found
      to increase significantly. Antibiotic-resistant bacterial infections are a
      growing problem in patient care. This in vitro research investigated the
      antimicrobial potential of the polymer released, broad spectrum, Cationic
      Steroidal Antimicrobial-13 (CSA-13) for challenges against 5 * 10(8) colony
      forming units (CFU) of methicillin-resistant Staphylococcus aureus (MRSA). It was
      hypothesized that a weight-to-weight (w/w) concentration of 18% CSA-13 in
      silicone would exhibit potent bactericidal potential when used as a controlled
      release device coating. When incorporated into a polymeric device coating, the
      18% (w/w) broad-spectrum polymer released CSA-13 antimicrobial eliminated 5 *
      10(8) CFU of MRSA within 8 h. In the future, these results will be utilized to
      develop a sheep model to assess CSA-13 for the prevention of perioperative device
      related infections in vivo.

PMID- 22623406
TI  - Taking a lesson from patients' recovery strategies to optimize training during
      robot-aided rehabilitation.
AB  - In robot-assisted neurorehabilitation, matching the task difficulty level to the
      patient's needs and abilities, both initially and as the relearning process
      progresses, can enhance the effectiveness of training and improve patients'
      motivation and outcome. This study presents a Progressive Task Regulation
      algorithm implemented in a robot for upper limb rehabilitation. It evaluates the
      patient's performance during training through the computation of robot-measured
      parameters, and automatically changes the features of the reaching movements,
      adapting the difficulty level of the motor task to the patient's abilities. In
      particular, it can select different types of assistance (time-triggered, activity
      triggered, and negative assistance) and implement varied therapy practice to
      promote generalization processes. The algorithm was tuned by assessing the
      performance data obtained in 22 chronic stroke patients who underwent robotic
      rehabilitation, in which the difficulty level of the task was manually adjusted
      by the therapist. Thus, we could verify the patient's recovery strategies and
      implement task transition rules to match both the patient's and therapist's
      behavior. In addition, the algorithm was tested in a sample of five chronic
      stroke patients. The findings show good agreement with the therapist decisions so
      indicating that it could be useful for the implementation of training protocols
      allowing individualized and gradual treatment of upper limb disabilities in
      patients after stroke. The application of this algorithm during robot-assisted
      therapy should allow an easier management of the different motor tasks
      administered during training, thereby facilitating the therapist's activity in
      the treatment of different pathologic conditions of the neuromuscular system.

PMID- 22623405
TI  - PRRT2 mutations are the major cause of benign familial infantile seizures.
AB  - Mutations in PRRT2 have been described in paroxysmal kinesigenic dyskinesia (PKD)
      and infantile convulsions with choreoathetosis (PKD with infantile seizures), and
      recently also in some families with benign familial infantile seizures (BFIS)
      alone. We analyzed PRRT2 in 49 families and three sporadic cases with BFIS only
      of Italian, German, Turkish, and Japanese origin and identified the previously
      described mutation c.649dupC in an unstable series of nine cytosines to occur in
      39 of our families and one sporadic case (77% of index cases). Furthermore, three
      novel mutations were found in three other families, whereas 17% of our index
      cases did not show PRRT2 mutations, including a large family with late-onset BFIS
      and febrile seizures. Our study further establishes PRRT2 as the major gene for
      BFIS alone.

PMID- 22623407
TI  - Robot training of upper limb in multiple sclerosis: comparing protocols with or
      without manipulative task components.
AB  - In this pilot study, we compared two protocols for robot-based rehabilitation of
      upper limb in multiple sclerosis (MS): a protocol involving reaching tasks (RT)
      requiring arm transport only and a protocol requiring both objects' reaching and
      manipulation (RMT). Twenty-two MS subjects were assigned to RT or RMT group. Both
      protocols consisted of eight sessions. During RT training, subjects moved the
      handle of a planar robotic manipulandum toward circular targets displayed on a
      screen. RMT protocol required patients to reach and manipulate real objects, by
      moving the robotic arm equipped with a handle which left the hand free for distal
      tasks. In both trainings, the robot generated resistive and perturbing forces.
      Subjects were evaluated with clinical and instrumental tests. The results
      confirmed that MS patients maintained the ability to adapt to the robot-generated
      forces and that the rate of motor learning increased across sessions. Robot
      therapy significantly reduced arm tremor and improved arm kinematics and
      functional ability. Compared to RT, RMT protocol induced a significantly larger
      improvement in movements involving grasp (improvement in Grasp ARAT sub-score:
      RMT 77.4%, RT 29.5%, p=0.035) but not precision grip. Future studies are needed
      to evaluate if longer trainings and the use of robotic handles would
      significantly improve also fine manipulation.

PMID- 22623408
TI  - Influence of solvent and bridge structure in alkylthio-substituted triphenylamine
      dyes on the photovoltaic properties of dye-sensitized solar cells.
AB  - Three new triphenylamine dyes that contain alkylthio-substituted thiophenes with
      a low bandgap as a pi-conjugated bridge unit were designed and synthesized for
      organic dye-sensitized solar cells (DSSCs). The effects of the structural
      differences in terms of the position, number, and shape of the alkylthio
      substituents in the thiophene bridge on the photophysical properties of the dye
      and the photovoltaic performance of the DSSC were investigated. The introduction
      of an alkylthio substituent at the 3-position of thiophene led to a decrease in
      the degree of redshift and the value of the molar extinction coefficient of the
      charge-transfer band, and the substituent with a bridged structure led to a
      larger redshift than that of the open-chain structure. The introduction of bulky
      and hydrophobic side chains decreased the short-circuit photocurrent (J(sc)),
      which was caused by the reduced amount of dye adsorbed on TiO(2). This resulted
      in a decrease in the overall conversion efficiency (eta), even though it could
      improve the open-circuit voltage (V(oc)) due to the retardation of charge
      recombination. Furthermore, the change in solvents for TiO(2) sensitization had a
      critical effect on the performance of the resulting DSSCs due to the different
      amounts of dye adsorbed. Based on the optimized dye bath and molecular structure,
      the ethylene dithio-substituted dye (ATT3) showed a prominent solar-to
      electricity conversion efficiency of 5.20%.

PMID- 22623409
TI  - Quantitative proteomics of primary tumors with varying metastatic capabilities
      using stable isotope-labeled proteins of multiple histogenic origins.
AB  - The development of metastasis is a complex, multistep process that remains poorly
      defined. To identify proteins involved in the colonization phase of the
      metastatic process, we compared the proteome of tumors derived from inoculation
      of a panel of isogenic human cancer cell lines with different metastatic
      capabilities into the mammary fat pad of immunodeficient mice. Using a protein
      standard generated by SILAC-labeling, a total of 675 proteins were identified and
      30 were differentially expressed between at least two of the tumors. The protein
      standard contained the proteomes of seven cell lines from multiple histogenic
      origins and displayed superior features compared to standard super-SILAC. The
      expression of some proteins correlated with metastatic capabilities, such as
      myosin-9 (nonmuscle myosin II A) and L-lactate dehydrogenase A, while the
      expression of elongation factor tu correlated inversely to metastatic
      capabilities. The expression of these proteins was biochemically validated, and
      expression of myosin-9 in clinical breast cancer samples was further shown to be
      altered in primary tumors versus corresponding lymph node metastasis. Our study
      demonstrates an improved strategy for quantitative comparison of an unlimited
      number of tumor tissues, and provides novel insights into key proteins associated
      with the colonization phase of metastasis formation.

PMID- 22623410
TI  - Workflow for analysis of high mass accuracy salivary data set using MaxQuant and
      ProteinPilot search algorithm.
AB  - LTQ Orbitrap data analyzed with ProteinPilot can be further improved by MaxQuant
      raw data processing, which utilizes precursor-level high mass accuracy data for
      peak processing and MGF creation. In particular, ProteinPilot results from
      MaxQuant-processed peaklists for Orbitrap data sets resulted in improved spectral
      utilization due to an improved peaklist quality with higher precision and high
      precursor mass accuracy (HPMA). The output and postsearch analysis tools of both
      workflows were utilized for previously unexplored features of a three-dimensional
      fractionated and hexapeptide library (ProteoMiner) treated whole saliva data set
      comprising 200 fractions. ProteinPilot's ability to simultaneously predict
      multiple modifications showed an advantage from ProteoMiner treatment for
      modified peptide identification. We demonstrate that complementary approaches in
      the analysis pipeline provide comprehensive results for the whole saliva data set
      acquired on an LTQ Orbitrap. Overall our results establish a workflow for
      improved protein identification from high mass accuracy data.

PMID- 22623411
TI  - Intestinal and liver changes after chronic ketamine and ketamine plus alcohol
      treatment.
AB  - The effects of long-term chronic ketamine treatment on the intestine and the
      liver were studied in the ICR mice which had daily intraperitoneal injection of
      ketamine at 30 mg/kg per day for 7 months. The intestine showed no significant
      pathology after treatment but had a decrease of the positive sites of
      proliferative cell nuclear antigen in the mucosae of the intestines after
      ketamine and ketamine plus alcohol (added in the last month) treatment. No
      significant apoptosis (via TUNEL) nor necrosis (via lactic acid dehydrogenase)
      was detected in the intestines of all control and ketamine-treated groups, with
      the exception of an increase of lactic acid dehydrogenase in the mucosae of the
      intestines of the ketamine plus alcohol group. In the liver, loss of glycogen was
      observed in animals after ketamine and ketamine plus alcohol treatment, in
      addition to the pathology reported in a previous work. The decrease in quantity
      of glycogen in the liver reflected either a failure of glycogen synthesis from
      glucose or an increase of glycogenolysis in the liver.

PMID- 22623412
TI  - Degradable amorphous scaffolds with enhanced mechanical properties and
      homogeneous cell distribution produced by a three-dimensional fiber deposition
      method.
AB  - The mechanical properties of amorphous, degradable, and highly porous
      poly(lactide-co-caprolactone) structures have been improved by using a 3D fiber
      deposition (3DF) method. Two designs of 3DF scaffolds, with 45 degrees  and 90
      degrees  layer rotation, were printed and compared with scaffolds produced by a
      salt-leaching method. The scaffolds had a porosity range from 64% to 82% and a
      high interconnectivity, measured by micro-computer tomography. The 3DF scaffolds
      had 8-9 times higher compressive stiffness and 3-5 times higher tensile stiffness
      than the salt-leached scaffolds. There was a distinct decrease in the molecular
      weight during printing as a consequence of the high temperature. The chain
      microstructure was, however, not affected; the glass transition temperature and
      the decomposition temperature were constant. Human OsteoBlast-like cells were
      cultured in vitro and the cell morphology and distribution were observed by
      scanning electron microscopy and fluorescence microscopy. The cell distribution
      on the 3DF scaffolds was more homogeneous than the salt-leached scaffolds,
      suggesting that 3DF scaffolds are more suitable as porous biomaterials for tissue
      engineering. These results show that it is possible to design and optimize the
      properties of amorphous polymer scaffolds. The 3DF method produce amorphous
      degradable poly(lactide-co-caprolactone) that are strong and particularly
      suitable for cell proliferation.

PMID- 22623413
TI  - Pharmacologically dosed oral glutamine reduces myocardial injury in patients
      undergoing cardiac surgery: a randomized pilot feasibility trial.
AB  - BACKGROUND AND OBJECTIVE: Glutamine (GLN) has been shown to protect against in
      vitro and in vivo myocardial injury. In humans, perioperative
      ischemia/reperfusion (I/R) injury during cardiac surgery is associated with
      higher morbidity and mortality. The objective of this safety and feasibility
      pilot trial was to determine if pharmacologically dosed, preoperative oral GLN
      attenuates myocardial injury in cardiac surgery patients. METHODS: Patients
      undergoing elective cardiac surgery, requiring cardiopulmonary bypass, were
      enrolled in a randomized, double-blind pilot trial to receive 25 g twice of oral
      alanyl-glutamine (GLN; n = 7) or maltodextrin (CONT; n = 7) daily for 3 days
      preoperatively. Serum troponin (TROP I), creatine kinase (CK-MB), and myoglobin
      (MG) were measured at multiple perioperative time points. Clinical outcomes were
      also recorded and assessed. RESULTS: GLN therapy significantly decreased TROP I
      levels at 24, 48, and 72 hours postoperatively (all P < .05) vs CONT. GLN also
      reduced CK-MB at 24 and 48 hours (P < .05, P < .001) vs CONT. MG was reduced at
      24 hours vs control (P = .0397). GLN also significantly reduced pooled clinical
      complications vs CONT (P = .03). CONCLUSION: This pilot study showed that
      pharmacologically dosed oral GLN therapy prior to cardiac surgery was safe, well
      tolerated, and feasible. GLN therapy reduced myocardial injury and clinical
      complications in this small randomized, blinded feasibility trial. These data
      indicate that a larger trial of preoperative GLN therapy in patients undergoing
      cardiac surgery is needed to confirm clinical benefit.

PMID- 22623414
TI  - The Arabidopsis gene hypersensitive to phosphate starvation 3 encodes ethylene
      overproduction 1.
AB  - When plants are subjected to a deficiency in inorganic phosphate (Pi), they
      exhibit an array of responses to cope with this nutritional stress. In this work,
      we have characterized two Arabidopsis mutants, hps3-1 and hps3-2 (hypersensitive
      to Pi starvation 3), that have altered expression of Pi starvation-induced (PSI)
      genes and enhanced production of acid phosphatase (APase) when grown under either
      Pi sufficiency or deficiency conditions. hps3-1 and hps3-2, however, accumulate
      less anthocyanin than the wild type when grown on a Pi-deficient medium.
      Molecular cloning indicated that the phenotypes of hps3 mutants were caused by
      mutations within the ETO1 (ETHYLENE OVERPRODUCTION 1) gene. In Arabidopsis, ETO1
      encodes a negative regulator of ethylene biosynthesis, and mutation of ETO1
      causes Arabidopsis seedlings to overproduce ethylene. The ethylene biosynthesis
      inhibitor aminoethoxyvinyl glycine or the ethylene perception inhibitor Ag(+)
      suppressed all the mutant phenotypes of hps3. Taken together, these results
      provide further genetic evidence that ethylene is an important regulator of
      multiple plant responses to Pi starvation. Furthermore, we found that a change in
      ethylene level has differential effects on the expression of PSI genes,
      maintenance of Pi homeostasis, production of APase and accumulation of
      anthocyanin. We also demonstrated that ethylene signaling mainly regulates the
      activity of root surface-associated APases rather than total APase activity.

PMID- 22623416
TI  - Selective cycloaddition of tetracyanoethene (TCNE) and 7,7,8,8-tetracyano-p
      quinodimethane (TCNQ) to afford meso-substituted phenylethynyl porphyrins.
AB  - pi-Extended TCBD-porphyrins that contained a 1,1,4,4-tetracyanobuta-1,3-diene
      unit were prepared by a highly efficient [2+2] cycloaddition of tetracyanoethene
      (TCNE) or 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) with meso-substituted trans
      A(2)B(2)-porphyrins that contained two phenylethynyl groups, followed by a retro
      electrocyclization reaction. Depending on the electronic properties of the
      arylethynyl groups, the cycloaddition reaction took place exclusively on either
      one or two ethynyl moieties with high yield. The addition of TCNQ proceeded with
      complete regioselectivity. The resulting pi-expanded TCBD-porphyrins had a
      hypsochromically shifted Soret band and showed unique, broad absorption in the
      visible region.

PMID- 22623415
TI  - The microRNA pathway genes AGO1, HEN1 and HYL1 participate in leaf proximal
      distal, venation and stomatal patterning in Arabidopsis.
AB  - We isolated Arabidopsis thaliana mutants with incurved vegetative leaves.
      Positional cloning of incurvata8 (icu8), icu9 and icu15 has identified them as
      new loss-of-function alleles of the HYPONASTIC LEAVES1 (HYL1), ARGONAUTE1 (AGO1)
      and HUA ENHANCER1 (HEN1) genes, respectively, which encode known components of
      the microRNA pathway. The morphological and histological characterization of
      these mutants and of dicer-like1-9 indicates that small RNAs participate in the
      proximal-distal and adaxial-abaxial patterning of leaves, as well as in stomatal
      number establishment. The abnormal vasculature of ago1 and hyl1 leaves also
      suggests a role for AGO1 and HYL1 in venation patterning. Our mutants expand the
      allelic series of AGO1, HYL1 and HEN1, and might help to understand the
      developmental and cellular significance of miRNA-mediated posttranscriptional
      regulation.

PMID- 22623417
TI  - The use of LC-MS to identify differentially expressed proteins in docetaxel
      resistant prostate cancer cell lines.
AB  - Docetaxel is a taxane-derived chemotherapy drug that has been approved for
      treatment of prostate cancer. While docetaxel is frequently used as a treatment
      for hormone-refractory prostate cancer, a subset of patients either do not
      respond to this treatment or those that do respond eventually become resistant to
      the drug over time. Resistance to docetaxel is complex and multi-factoral and
      further understanding of the cellular biochemistry underlying resistance is vital
      to improve treatment efficacy. To identify proteins altered in the resistant
      phenotype, three parental cell lines DU145, 22RV1 and PC-3, as well as their
      docetaxel resistant sub-lines, were subjected to quantitative label-free LC-MS
      proteomic profiling. A total of 189 significant (p < 0.05) protein abundance
      changes were identified in the DU145 resistant sub-lines, 254 in the 22RV1 sub
      lines, and 51 and 72 in the 8 and 12 nM resistant PC-3 sub-lines, respectively.
      From these, 29 proteins demonstrated a significant (p < 0.05) fold change across
      two or more resistant variants. These included proteins indicative of an
      epithelial-to-mesenchemyl transition as well as altered heat shock response
      elements.

PMID- 22623418
TI  - Comparative label-free LC-MS/MS analysis of colorectal adenocarcinoma and
      metastatic cells treated with 5-fluorouracil.
AB  - A label-free mass spectrometric strategy was used to examine the effect of 5
      fluorouracil (5-FU) on the primary and metastatic colon carcinoma cell lines,
      SW480 and SW620, with and without treatment. 5-FU is the most common
      chemotherapeutic treatment for colon cancer. Pooled biological replicates were
      analyzed by nanoLC-MS/MS and protein quantification was determined via spectral
      counting. Phenotypic and proteomic changes were evident and often similar in both
      cell lines. The SW620 cells were more resistant to 5-FU treatment, with an IC(50)
      2.7-fold higher than that for SW480. In addition, both cell lines showed
      pronounced abundance changes in pathways relating to antioxidative stress
      response and cell adhesion remodeling due to 5-FU treatment. For example, the
      detoxification enzyme NQO1 was increased with treatment in both cell lines, while
      disparate members of the peroxiredoxin family, PRDX2 or PRDX5 and PRDX6, were
      elevated with 5-FU exposure in either SW480 or SW620, respectively. Cell adhesion
      associated proteins CTNNB1 and RhoA showed decreased expression with 5-FU
      treatment in both cell lines. The differential quantitative response in the
      proteomes of these patient-matched cell lines to drug treatment underscores the
      subtle molecular differences separating primary and metastatic cancer cells.

PMID- 22623419
TI  - Chemo-enzymatic conversion of glucose into 5-hydroxymethylfurfural in seawater.
AB  - Do you sea water? Water consumption will be a challenge in biorefineries, and the
      use of non-drinkable sources of water will be preferred. Herein, glucose is
      converted into 5-hydroxymethylfurfural (HMF) in a chemo-enzymatic one-pot, two
      step procedure, involving immobilized glucose isomerase to produce fructose and
      oxalic acid to dehydrate it to HMF.

PMID- 22623420
TI  - Impact of ArcA loss in Shewanella oneidensis revealed by comparative proteomics
      under aerobic and anaerobic conditions.
AB  - Shewanella inhabit a wide variety of niches in nature and can utilize a broad
      spectrum of electron acceptors under anaerobic conditions. How they modulate
      their gene expression to adapt is poorly understood. ArcA, homologue of a global
      regulator controlling hundreds of genes involved in aerobic and anaerobic
      respiration in E. coli, was shown to be important in aerobiosis/anaerobiosis of
      S. oneidensis as well. Loss of ArcA, in addition to altering transcription of
      many genes, resulted in impaired growth under aerobic condition, which was not
      observed in E. coli. To further characterize the impact of ArcA loss on gene
      expression on the level of proteome under aerobic and anaerobic conditions,
      liquid-chromatography-mass-spectrometry (LC-MS) based proteomic approach was
      employed. Results show that ArcA loss led to globally altered gene expression,
      generally consistent with that observed with transcripts. Comparison of
      transcriptomic and proteomic data permitted identification of 17 high-confidence
      ArcA targets. Moreover, our data indicate that ArcA is required for regulation of
      cytochrome c proteins, and the menaquinone level may play a role in regulating
      ArcA as in E. coli. Proteomic data-guided growth assay revealed that the aerobic
      growth defect of ArcA mutant is presumably due to impaired peptide utilization.

PMID- 22623421
TI  - Proteomic analysis of gingival crevicular fluid for discovery of novel
      periodontal disease markers.
AB  - The protein composition of gingival crevicular fluid (GCF) may reflect the
      pathophysiology of periodontal diseases. A standard GCF proteomic pattern of
      healthy individuals would serve as a reference to identify biomarkers of
      periodontal diseases by proteome analyses. However, protein profiles of GCF
      obtained from apparently healthy individuals have not been well explored. As a
      step toward detection of proteomic biomarkers for periodontal diseases, we
      applied both gel-based and gel-free methods to analyze GCF obtained from healthy
      subjects as compared with supragingival saliva. To ensure optimized protein
      extraction from GCF, a novel protocol was developed. The proteins in GCF were
      extracted with high yield by urea buffer combined with ultrafiltration and the
      intensity of spots with supragingival saliva and GCF was compared using agarose
      two-dimensional electrophoresis. Eight protein spots were found to be
      significantly more intense in GCF. They included superoxide dismutase 1 (SOD1),
      apolipoprotein A-I (ApoA-I), and dermcidin (DCD). Moreover, GCF proteins from
      healthy subjects were broken down into small peptide fragments and then analyzed
      directly by LC-MS/MS analysis. A total of 327 proteins including ApoA-I, SOD1,
      and DCD were identified in GCF. These results may serve as reference for future
      proteomic studies searching for GCF biomarkers of periodontal diseases.

PMID- 22623422
TI  - Efficient expansion of mesenchymal stem cells from mouse bone marrow under
      hypoxic conditions.
AB  - To realize the therapeutic potential of mesenchymal stem cells (MSCs), a large
      number of high-quality MSCs isolated from different species, such as mouse, were
      acquired for preclinical animal studies. Surprisingly, isolation and purification
      of mouse MSCs (mMSCs) is arduous because of the low frequency of MSCs and
      contamination of haematopoietic cells in culture. We have developed a method
      based on low density and hypoxic culture to isolate and expand mMSCs from
      different strains, including BALB/c, C57BL/6J, FVB/N and DBA/2. The cells from
      all of the strains expanded more rapidly when plated at low density in hypoxic
      culture compared with normoxic culture. These cells expressed CD44, CD105, CD29
      and Sca-1 markers but not CD11b, CD34, CD45 and CD31 markers. Moreover, they were
      able to differentiate along osteoblastic, adipocytic and chondrocytic lineages.
      In conclusion, we have developed a robust method for isolation and expansion of
      mMSCs by combining low-density culture with hypoxic culture.

PMID- 22623423
TI  - A comparison of the bovine uterine and plasma proteome using iTRAQ proteomics.
AB  - Early embryo loss is a key factor affecting fertility in dairy and beef herds.
      Prior to implantation, the bovine embryo spends around 16 days free-floating in
      the uterine environment and is dependent on the composition of uterine fluid for
      normal growth and development. However, there is a lack of information regarding
      the protein composition of the bovine uterus and how it relates to plasma. In
      this study, uterine flushings (UF) (n = 6) and blood plasma (n = 4) were
      collected from beef heifers on day 7 of the oestrous cycle, albumin depleted and
      compared using iTRAQ proteomics. A total of 35 proteins were higher and 18 were
      lower in UF including metabolic enzymes, proteins with anti-oxidant activity and
      those involved in modulation of the immune response. This study confirms the
      dynamic nature of the bovine uterine proteome and that it differs from plasma.
      Factors affecting the uterine proteome and how it impacts on embryo survival
      warrant further study.

PMID- 22623425
TI  - Comparison of the effects of pulsatile cardiopulmonary bypass, non-pulsatile
      cardiopulmonary bypass and off-pump coronary artery bypass grafting on the
      respiratory system and serum carbonyl.
AB  - BACKGROUND: We aimed to investigate the effects of off-pump coronary artery
      bypass grafting (CABG), pulsatile cardiopulmonary bypass (CPB), and non-pulsatile
      CPB techniques on oxidative stress and the respiratory system in the current
      study. MATERIALS AND METHODS: The patients were allocated into three different
      groups according to perfusion techniques, as follows: off-pump CABG group (n=10);
      pulsatile CPB (n=11); and non-pulsatile CPB group (n=11). Serum carbonyl level
      was measured and a pulmonary function test was performed preoperatively and
      postoperatively. RESULTS: The postoperative increase in the carbonyl level was
      significantly lower in the off-pump CABG group compared to the other two groups,
      while there was no significant difference between the pulsatile and non-pulsatile
      CPB groups with respect to carbonyl levels. Arterial partial pressure of oxygen,
      forced expiratory volume in one second, and forced vital capacity were
      significantly higher in the off-pump CABG group compared to other two groups in
      the postoperative period. CONCLUSION: We found that off-pump CABG had less
      negative effects on oxidative stress and the respiratory system compared to
      pulsatile CPB and non-pulsatile CPB techniques. Additionally, there was no
      significant difference between pulsatile and non-pulsatile CPB.

PMID- 22623424
TI  - IQcat: multiplexed protein quantification by isoelectric QconCAT.
AB  - Expression of isotopically labeled peptide standards as artificial concatamers
      (QconCATs) allows for the multiplex quantification of proteins in unlabeled
      samples by mass spectrometry. We have developed a generalizable QconCAT design
      strategy, which we term IQcat, wherein concatenated peptides are binned by pI to
      facilitate MS-sample enrichment by isoelectric focusing. Our method utilizes a
      rapid (~2 weeks), inexpensive and scalable purification of arg/lys labeled IQcat
      standards in the Escherichia coli auxotroph AT713. With this pipeline, we assess
      the fidelity of IQcat-based absolute quantification for ten yeast proteins over a
      broad concentration range in a single information-rich isoelectric fraction. The
      technique is further employed for a quantitative study of androgen-dependent
      protein expression in cultured prostate cancer cells.

PMID- 22623426
TI  - Novel methods of myocardial protection and de-airing for complex descending
      aortic aneurysm surgery.
AB  - A 64-year-old male who had previously undergone an aortic valve replacement and
      replacement of the ascending aorta presented with an 8 cm descending aortic
      aneurysm. A left thoracotomy was required to allow replacement of the aorta.
      However, due to longitudinal as well as transverse expansion, visualisation of
      the aortic arch was compromised, preventing cross-clamping of the proximal aorta.
      Cardiopulmonary bypass and deep hypothermic circulatory arrest were, therefore,
      required. An unusual method of cardioplegia delivery was used for myocardial
      protection, utilising a Foley catheter under direct vision as an alternative to
      more expensive percutaneous peripheral endoclamp devices. We also describe an
      unusual cardiopulmonary bypass circuit, with the dual use of a left atrial
      cannula for venting and also for re-establishing perfusion during de-airing.

PMID- 22623429
TI  - Why anger and disappointment affect other's bargaining behavior differently: the
      moderating role of power and the mediating role of reciprocal and complementary
      emotions.
AB  - In two experiments, the authors investigated the interpersonal effects of anger
      and disappointment in negotiations. Whereas previous research focused on the
      informational inferences that bargainers make based on others' emotions, this
      article emphasizes the importance of affective reactions. The findings of this
      study show that anger evoked a complementary emotion (fear) in targets when
      reported by a high-power bargainer but evoked a reciprocal emotion (anger) when
      reported by a low-power bargainer. This reciprocal anger led participants to
      offer less to low-power counterparts who reported anger. Disappointed bargainers,
      however, evoked a complementary emotion (guilt) in participants and increased
      offers, regardless of the bargainer's power position.

PMID- 22623428
TI  - Proteomic analysis of alpha4beta1 integrin adhesion complexes reveals alpha
      subunit-dependent protein recruitment.
AB  - Integrin adhesion receptors mediate cell-cell and cell-extracellular matrix
      interactions, which control cell morphology and migration, differentiation, and
      tissue integrity. Integrins recruit multimolecular adhesion complexes to their
      cytoplasmic domains, which provide structural and mechanosensitive signaling
      connections between the extracellular and intracellular milieux. The different
      functions of specific integrin heterodimers, such as alpha4beta1 and alpha5beta1,
      have been attributed to distinct signal transduction mechanisms that are
      initiated by selective recruitment of adhesion complex components to integrin
      cytoplasmic tails. Here, we report the isolation of ligand-induced adhesion
      complexes associated with wild-type alpha4beta1 integrin, an activated
      alpha4beta1 variant in the absence of the alpha cytoplasmic domain (X4C0), and a
      chimeric alpha4beta1 variant with alpha5 leg and cytoplasmic domains
      (alpha4Palpha5L), and the cataloguing of their proteomes by MS. Using
      hierarchical clustering and interaction network analyses, we detail the
      differential recruitment of proteins and highlight enrichment patterns of
      proteins to distinct adhesion complexes. We identify previously unreported
      components of integrin adhesion complexes and observe receptor-specific
      enrichment of molecules with previously reported links to cell migration and cell
      signaling processes. Furthermore, we demonstrate colocalization of MYO18A with
      active integrin in migrating cells. These datasets provide a resource for future
      studies of integrin receptor-specific signaling events.

PMID- 22623427
TI  - Neuroimmune mechanisms in fetal alcohol spectrum disorder.
AB  - Fetal alcohol spectrum disorder (FASD) is a major health concern worldwide and
      results from maternal consumption of alcohol during pregnancy. It produces
      tremendous individual, social, and economic losses. This review will first
      summarize the structural, functional, and behavior changes seen in FASD. The
      development of the neuroimmune system will be then be described with particular
      emphasis on the role of microglial cells in the normal regulation of homeostatic
      function in the central nervous system (CNS) including synaptic transmission. The
      impact of alcohol on the neuroimmune system in the developing CNS will be
      discussed in the context of several key immune molecules and signaling pathways
      involved in neuroimmune mechanisms that contribute to FASD. This review concludes
      with a summary of the development of early therapeutic approaches utilizing
      immunosuppressive drugs to target alcohol-induced pathologies. The significant
      role played by neuroimmune mechanisms in alcohol addiction and pathology provides
      a focus for future research aimed at understanding and treating the consequences
      of FASD.

PMID- 22623430
TI  - Facial Action Recognition Combining Heterogeneous Features via Multikernel
      Learning.
AB  - This paper presents our response to the first international challenge on facial
      emotion recognition and analysis. We propose to combine different types of
      features to automatically detect action units (AUs) in facial images. We use one
      multikernel support vector machine (SVM) for each AU we want to detect. The first
      kernel matrix is computed using local Gabor binary pattern histograms and a
      histogram intersection kernel. The second kernel matrix is computed from active
      appearance model coefficients and a radial basis function kernel. During the
      training step, we combine these two types of features using the recently proposed
      SimpleMKL algorithm. SVM outputs are then averaged to exploit temporal
      information in the sequence. To evaluate our system, we perform deep
      experimentation on several key issues: influence of features and kernel function
      in histogram-based SVM approaches, influence of spatially independent information
      versus geometric local appearance information and benefits of combining both,
      sensitivity to training data, and interest of temporal context adaptation. We
      also compare our results with those of the other participants and try to explain
      why our method had the best performance during the facial expression recognition
      and analysis challenge. 

PMID- 22623431
TI  - Hinfinity model reduction of Takagi-Sugeno fuzzy stochastic systems.
AB  - This paper is concerned with the problem of  H(infinity)  model reduction for
      Takagi-Sugeno (T-S) fuzzy stochastic systems. For a given mean-square stable T-S
      fuzzy stochastic system, our attention is focused on the construction of a
      reduced-order model, which not only approximates the original system well with an
      H(infinity)  performance but also translates it into a linear lower dimensional
      system. Then, the model reduction is converted into a convex optimization problem
      by using a linearization procedure, and a projection approach is also presented,
      which casts the model reduction into a sequential minimization problem subject to
      linear matrix inequality constraints by employing the cone complementary
      linearization algorithm. Finally, two numerical examples are provided to
      illustrate the effectiveness of the proposed methods.

PMID- 22623432
TI  - Neural-network-based decentralized adaptive output-feedback control for large
      scale stochastic nonlinear systems.
AB  - This paper focuses on the problem of neural-network-based decentralized adaptive
      output-feedback control for a class of nonlinear strict-feedback large-scale
      stochastic systems. The dynamic surface control technique is used to avoid the
      explosion of computational complexity in the backstepping design process. A novel
      direct adaptive neural network approximation method is proposed to approximate
      the unknown and desired control input signals instead of the unknown nonlinear
      functions. It is shown that the designed controller can guarantee all the signals
      in the closed-loop system to be semiglobally uniformly ultimately bounded in a
      mean square. Simulation results are provided to demonstrate the effectiveness of
      the developed control design approach.

PMID- 22623433
TI  - Supervised latent linear Gaussian process latent variable model for
      dimensionality reduction.
AB  - The Gaussian process (GP) latent variable model (GPLVM) has the capability of
      learning low-dimensional manifold from highly nonlinear data of high
      dimensionality. As an unsupervised dimensionality reduction (DR) algorithm, the
      GPLVM has been successfully applied in many areas. However, in its current
      setting, GPLVM is unable to use label information, which is available for many
      tasks; therefore, researchers proposed many kinds of extensions to the GPLVM in
      order to utilize extra information, among which the supervised GPLVM (SGPLVM) has
      shown better performance compared with other SGPLVM extensions. However, the
      SGPLVM suffers in its high computational complexity. Bearing in mind the issues
      of the complexity and the need of incorporating additionally available
      information, in this paper, we propose a novel SGPLVM, called supervised latent
      linear GPLVM (SLLGPLVM). Our approach is motivated by both SGPLVM and supervised
      probabilistic principal component analysis (SPPCA). The proposed SLLGPLVM can be
      viewed as an appropriate compromise between the SGPLVM and the SPPCA.
      Furthermore, it is also appropriate to interpret the SLLGPLVM as a semiparametric
      regression model for supervised DR by making use of the GP to model the unknown
      smooth link function. Complexity analysis and experiments show that the developed
      SLLGPLVM outperforms the SGPLVM not only in the computational complexity but also
      in its accuracy. We also compared the SLLGPLVM with two classical supervised
      classifiers, i.e., a GP classifier and a support vector machine, to illustrate
      the advantages of the proposed model.

PMID- 22623434
TI  - A distributed trust evaluation model and its application scenarios for medical
      sensor networks.
AB  - The development of medical sensor networks (MSNs) is imperative for e-healthcare,
      but security remains a formidable challenge yet to be resolved. Traditional
      cryptographic mechanisms do not suffice given the unique characteristics of MSNs,
      and the fact that MSNs are susceptible to a variety of node misbehaviors. In such
      situations, the security and performance of MSNs depend on the cooperative and
      trust nature of the distributed nodes, and it is important for each node to
      evaluate the trustworthiness of other nodes. In this paper, we identify the
      unique features of MSNs and introduce relevant node behaviors, such as
      transmission rate and leaving time, into trust evaluation to detect malicious
      nodes. We then propose an applicationindependent and distributed trust evaluation
      model for MSNs. The trust management is carried out through the use of simple
      cryptographic techniques. Simulation results demonstrate that the proposed model
      can be used to effectively identify malicious behaviors and thereby exclude
      malicious nodes. This paper also reports the experimental results of the
      Collection Tree Protocol with the addition of our proposed model in a network of
      TelosB motes, which show that the network performance can be significantly
      improved in practice. Further, some suggestions are given on how to employ such a
      trust evaluation model in some application scenarios. 

PMID- 22623435
TI  - Correlation of magnetic resonance imaging-based knee cartilage T2 measurements
      and focal knee lesions with body mass index: thirty-six-month followup data from
      a longitudinal, observational multicenter study.
AB  - OBJECTIVE: To compare magnetic resonance imaging (MRI)-based knee cartilage T2
      measurements and focal knee lesions and 36-month changes in these parameters
      among knees of normal controls and knees of normal weight, overweight, and obese
      subjects with risk factors for knee osteoarthritis (OA). METHODS: A total of 267
      subjects ages 45-55 years from the Osteoarthritis Initiative database were
      analyzed in this study. Two hundred thirty-one subjects had risk factors for knee
      OA, but no radiographic OA (Kellgren/Lawrence score <=1) at baseline. Thirty-six
      subjects were normal controls. Subjects with OA risk factors were stratified in 3
      groups: normal weight (n = 78), overweight (n = 84), and obese (n = 69). All
      subjects underwent 3T MRI of the right knee at baseline and after 36 months.
      Focal knee lesions were assessed and cartilage T2 measurements (mean T2 and T2
      texture analysis) were performed. RESULTS: The baseline prevalence and severity
      of meniscal and cartilage lesions were highest in obese subjects and lowest in
      normal controls (P < 0.05). Obese subjects had the highest mean T2 values and the
      most heterogeneous cartilage (as assessed by T2 texture analysis), while normal
      controls had the lowest mean T2 values and the most homogeneous cartilage at
      baseline (P < 0.05). Increased body mass index (BMI) was significantly (P < 0.05)
      associated with greater progression of cartilage lesions and constantly elevated
      cartilage T2 entropy over 36 months. CONCLUSION: In preclinical OA, increased BMI
      is associated with more severe cartilage degeneration as assessed by both
      morphologic and quantitative MRI measurements.

PMID- 22623436
TI  - Effects of plant sterols and stanols on intestinal cholesterol metabolism:
      suggested mechanisms from past to present.
AB  - Plant sterols and stanols are natural food ingredients found in plants. It was
      already shown in 1950 that they lower serum low-density lipoprotein cholesterol
      (LDL-C) concentrations. Meta-analysis has reported that a daily intake of 2.5 g
      plant sterols/stanols reduced serum LDL-C concentrations up to 10%. Despite many
      studies, the underlying mechanism remains to be elucidated. Therefore, the
      proposed mechanisms that have been presented over the past decades will be
      described and discussed in the context of the current knowledge. In the early
      days, it was suggested that plant sterols/stanols compete with intestinal
      cholesterol for incorporation into mixed micelles as well as into chylomicrons.
      Next, the focus shifted toward cellular processes. In particular, a role for
      sterol transporters localized in the membranes of enterocytes was suggested. All
      these processes ultimately lowered intestinal cholesterol absorption. More
      recently, the existence of a direct secretion of cholesterol from the circulation
      into the intestinal lumen was described. First results in animal studies
      suggested that plant sterols/stanols activate this pathway, which also explains
      the increased fecal neutral sterol content and as such could explain the
      cholesterol-lowering activity of plant sterols/stanols.

PMID- 22623437
TI  - A robust, efficient, and highly enantioselective method for synthesis of
      homopropargyl amines.

PMID- 22623438
TI  - Critical limb ischaemia--from art to evidence.

PMID- 22623439
TI  - The path from art to evidence in treating critical limb ischaemia--reflections on
      35 years' experience.
AB  - Despite numerous attempts, chronic critical limb ischaemia (CLI) has not been
      unequivocally defined as yet. Its epidemiology is poorly investigated and its
      prevalence probably higher than anticipated. It is accompanied by high mortality
      and morbidity irrespective of the way it is treated. Its management is very
      expensive. Additionally, the prevailing diabetes epidemic is increasing the need
      for revascularizations although there is a clear lack of evidence as to when to
      revascularize an ulcerated diabetic foot. The fast development of endovascular
      techniques blurs the vision as the window of opportunity for gathering proper
      evidence keeps narrowing. The notion of endovascular artistry prevails, but
      attempts to conduct proper studies with clear definitions, strict criteria and
      appropriate outcome measures in a standardised manner should continue--preferably
      using propensity scoring if randomised controlled trials are not possible. This
      review highlights some of the steps leading from art to evidence and illustrates
      the difficulties encountered along the path. In parallel with this overview, the
      progress of the treatment for CLI in Finland is described from the perspective of
      the work concluded at Helsinki University Central Hospital.

PMID- 22623440
TI  - Vascular laboratory for critical limb ischaemia.
AB  - This is a narrative review on vascular assessment for critical limb ischaemia in
      the past and present combining Finnish and Japanese experience.

PMID- 22623441
TI  - Role and management of coagulation disorders in peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) has often underlying risk factors, of which
      diabetes and cigarette smoking are the most common. Enhanced platelet activation
      and interaction with vessel wall associate with atherothrombotic disease, but
      also increased fibrinogen levels, thrombin generation and fibrin turnover are
      typical for PAD. The pathogenic role of fibrinogen, thrombin formation and fibrin
      degradation is suggested not only in acute thrombotic complications, but also in
      the stable form of PAD, where these markers associate with the functional
      severity (ankle-brachial blood pressure index). The coagulation-specific
      etiologies of PAD should be suspected if the atherothrombotic disease has severe
      manifestations, especially while the traditional risk factors are absent, or if
      the patient has also a history of venous thromboembolism. Malignant disease may
      be present in form of peripheral arterial thrombosis as well. Thrombophilia may
      expose patients to idiopathic thrombosis--both spontaneously and after vascular
      interventions. The management of these patients includes often combination
      therapies with antiplatelet agents and anticoagulants. Obviously, the strict
      policy to avoid risk factors and to treat them well in avoidance of progression
      of arterial disease is highly important. In the absence of published follow-up
      data the evidence to support the management strategies is weak and individual
      tailoring of efficacious and safe antithrombotic drug therapy remains our
      challenge. These patients benefit from continuous medical attention by the
      experts in the field of angiology. Management of PAD is an excellent example of
      the multidisciplinary approach where the hematologist meets the vascular surgeon
      or interventional radiologist to secure the best available patient care.

PMID- 22623442
TI  - Bypass grafts: the state of the art.
AB  - The treatment options for infra-renal arteriosclerotic occlusive (ASO) vascular
      disease have never been more varied. The history of open revascularization
      procedures now exceeds 60 years. This represents three generations of vascular
      surgeons, the most recent of whom have witnessed more than 30 years of
      endovascular surgery development and dissemination. Both open and endovascular
      treatments should be considered mature; moreover, we are improving our
      understanding of the strategies and tactics that lead to the clinical application
      of one approach instead of the other. There are other important factors in the
      choice of a treatment modality to be used for a specific patient. Prime among
      these is evolving patterns of occlusive disease and the increasing severity of
      arterial calcification.

PMID- 22623443
TI  - Hybrid procedures as a novel technique in the treatment of critical limb
      ischemia.
AB  - In hybrid reconstructions, patients are treated using both endovascular and open
      revascularization techniques simultaneously. In recent years, these multilevel
      reconstructions have been increasingly used especially by vascular surgeons as
      they have adopted new knowledge and endovascular skills and the endovascular
      techniques have evolved. The first reports of combined endovascular and open
      surgical procedures are from the 1970s. Since then, most reports have dealt with
      femoral endarterectomy or femoro-femoral bypass combined with inflow iliac
      percutaneous transluminal angioplasty (PTA) and stenting. Primary success rates
      have been high: 93%-100%. In our institution 213 hybrid procedures were performed
      during 2003-2011 with 98.6% technical success rate. The annual number of hybrid
      procedures ranged from 4 in 2004 to 73 in 2011. Inflow endovascular procedure was
      performed in 60% and outflow in 40 % of the cases. The proportion of the
      endovascular component performed by vascular surgeons increased from 0% in 2004
      to 86.3% in 2011. In the current report we review the results published in the
      literature, report our own experience and present some technical notes and cases.

PMID- 22623444
TI  - Why critical limb ischemia criteria are not applicable to diabetic foot and what
      the consequences are.
AB  - Neuropathy, peripheral arterial occlusive disease and microvascular disturbances
      are important factors contributing to foot problems in diabetic patients. In the
      diabetic foot with ischemia, the alterations in skin microvascular function are
      pronounced including severely reduced capillary circulation and abolished
      hyperaemic responses. These microvascular disturbances, which are superimposed on
      the already existing structural diabetic microangiopathy, are compatible with a
      state of "chronic capillary ischemia" and an increased shunting of blood through
      arteriovenous channels. This maldistribution of blood in skin microcirculation is
      not detected by measurement of peripheral blood pressure (systolic ankle blood
      pressure, systolic toe blood pressure). As indicated in several studies toe blood
      pressure is a poor predictor of local tissue perfusion, tissue survival and
      healing of chronic foot ulcers. Consequently, the disturbances in peripheral
      tissue perfusion of the diabetic foot may be underestimated leading to delayed
      vascular interventions and/or medical treatment. Thus, measurements of peripheral
      blood pressure, e.g. toe blood pressure, should be combined with investigations
      of local tissue perfusion in order to get an adequate estimation of peripheral
      tissue perfusion in diabetic patients. For this purpose local skin
      microcirculation can be investigated by transcutaneous oxygen tension of the
      forefoot. Also, due to these reasons, the threshold for revascularization should
      be lower in diabetic patients with foot ulcer.

PMID- 22623445
TI  - Surveillance after distal revascularization for critical limb ischaemia.
AB  - Patients with critical limb ischaemia (CLI) are usually elderly and suffer from
      several co-morbidities. The goal of surveillance after both endovascular and
      surgical revascularization for CLI is not only the protection of re-established
      distal perfusion and sustained ambulation but also the reduction of systemic
      atherothrombotic risk and mortality by ensuring continued best medical care.
      However, preferred format and rhythm of structured follow-up programs have
      remained controversial, mainly because of lack of compelling evidence. This
      review aims to summarize and to appraise available information critically.
      Thereby, it underlines the importance of systematic surveillance after both
      surgical and endovascular revascularization for CLI. Recent European guidelines
      are considered and areas of uncertainty are highlighted and discussed. According
      to currently available literature and recent guidelines, the early duplex scan is
      justified in all patients undergoing endovascular or surgical distal
      revascularization for CLI. There is no best level evidence supporting continued
      long term duplex surveillance of revascularizations with normal findings at early
      duplex scan, whereas those patients with abnormal early duplex scan or high risk
      revacularization are likely to benefit from continued duplex surveillance.
      Regular clinical follow-up is suggested and clinical deterioration should trigger
      duplex scanning to ensure revascularization patency.

PMID- 22623446
TI  - Angiosome theory: fact or fiction?
AB  - The angiosome concept delineates the human body into three-dimensional blocks of
      tissue fed by specific arterial and venous sources named "angiosomes." Adjacent
      angiosomes are connected by a vast compensatory collateral web, or "choke
      vessels." This concept may provide new information applicable to improving
      targeted revascularization of ischemic tissue lesions. A few dedicated studies
      available seem to favor this strategy, as encouraging ulcer healing and limb
      preservation are reported in connection with both bypass and endovascular
      techniques based on these principles. The theory on the angiosome model of
      revascularization (AMV) may help the clinician to better refine vessel selection,
      vascular access, and specific strategies in the revascularization of critically
      ischemic legs with tissue lesions. Specific applications of angiosome-guided
      revascularization were recently suggested for patients with diabetes or renal
      insufficiency, with ischemic tissue lesions of the lower limb, and extended large
      and medium-size collateral network decay. For these cases, the concept may allow
      deliberate arterial reconstruction following individual wound topographies in
      specific ischemic areas, although deprived from "rescue-vessel" supply. The AMV
      theory may contribute to a shift in common reperfusion options. However, the data
      available is suggestive and does not provide strong evidence as factors such as
      case mix and the severity of ischemia are unsatisfactorily controlled. At
      present, the evidence is scarce as to the effect of the severity of the arterial
      disease. In all comparisons, the groups treated are likely to be dissimilar and
      mismatched. The angiosome concept is postulated to be valid especially in
      diabetics, whose ischemic lesions tend to heal worse than those of non-diabetics.

PMID- 22623447
TI  - Health technology assessment in surgery.
AB  - This review focuses on how surgical methods should be assessed from a health
      technology perspective. The use of randomized controlled trials, population based
      registries, systematic literature research and the recently published IDEAL
      method are briefly discussed.

PMID- 22623448
TI  - End-stage renal disease and critical limb ischemia: a deadly combination?
AB  - OBJECTIVES: This study was planned to evaluate the prognostic impact of end-stage
      renal disease (ESRD) in patients with critical leg ischemia (CLI) undergoing
      infrainguinal revascularization. MATERIALS AND METHODS: 1425 patients who
      underwent infrainguinal revascularization for CLI were the subjects of the
      present analysis. Ninety-five patients had ESRD (eGFR < 15 ml/min/m2), and of
      them 66 (70%) underwent percutaneous transluminal angioplasty and 29 (30%)
      underwent bypass surgery. RESULTS: ESRD patients had significantly lower overall
      survival (at 3-year, 27.1% vs. 59.7%, p < 0.0001), leg salvage (at 3-year, 57.7%
      vs. 83.0%, p < 0.0001), and amputation free survival (at 3-year, 16.2% vs. 52.9%,
      p < 0.0001) than patients with no or less severe renal failure. The difference in
      survival was even greater between 86 one-to-one propensity matched pairs (at 3
      year, 23.1% vs. 67.3%, p < 0.0001). ESRD was an independent predictor of all
      cause mortality (RR 2.46, 95%CI 1.85-3.26). Logistic regression showed that age
      >= 75 years was the only independent predictor of 1-year all-cause mortality (OR
      4.92, 95%CI 1.32-18.36). Classification and regression tree analysis showed that
      age >= 75 years and, among younger patients, bypass surgery for leg ulcer and
      gangrene were associated with significantly higher 1-year mortality CONCLUSIONS:
      Lower limb revascularization in patients with CLI and end-stage renal failure is
      associated with favourable leg salvage. However, these patients have a very poor
      survival and this may jeopardize any attempt of revascularization. Further
      studies are needed to identify ESRD patients with acceptable life expectancy and
      who may benefit from lower limb revascularization.

PMID- 22623449
TI  - Diffuse idiopathic skeletal hyperostosis prevalence in subjects with severe
      atherosclerotic cardiovascular diseases.
AB  - OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by
      ossification of different entheseal sites. Several metabolic factors have been
      suggested to be involved in DISH development. We assessed the prevalence of DISH
      and its relationship to traditional vascular risk factors in a cohort of patients
      diagnosed with cardiovascular diseases. METHODS: Among the 521 consecutive
      patients admitted to the heart diseases rehabilitation program in our
      Rehabilitative Cardiology Unit, only those (n = 436) with recent coronary artery
      bypass grafting (CABG), a heart valve replacement (HVR), or congestive heart
      failure (CHF) were enrolled (45 CHF, 338 CABG, and 53 HVR). All patients
      underwent a rheumatologic examination, blood sample collections, and chest
      radiographs. Body mass index (BMI), blood pressure, and information about sex,
      age, smoking habit, and other vascular risk factors were recorded. DISH was
      established according to the Resnick and Niwayama criteria. RESULTS: In the
      setting (77.1% men), the mean +/- SD age was 65.44 +/- 9.66 years and the overall
      prevalence of DISH was 30.3%. A logistic regression analysis showed that both age
      (odds ratio [OR] 1.076, 95% confidence interval [95% CI] 1.044-1.109; P < 0.001)
      and obesity (OR 2.28, 95% CI 1.33-3.89; P = 0.003) were significant predictors of
      the presence of DISH. An increasing OR for the presence of DISH was found for
      increasing tertiles of age and BMI. No difference resulted according to other
      traditional vascular risk factors. BMI and age directly correlated with C
      reactive protein levels. CONCLUSION: The overall prevalence of DISH was 30.3%.
      This is expected because of the study population. Obese and older individuals
      exhibit a higher risk of DISH development.

PMID- 22623450
TI  - A general route to efficient functionalization of silicon quantum dots for high
      performance fluorescent probes.
AB  - A general technique for efficient surface modification of silicon nanocrystals is
      highly desirable for the development of silicon quantum dots (SiQDs) as
      fluorescent probes for biological applications. Herein, a facile microwave
      assisted hydrosilylation process for the preparation of stable SiQDs in a single
      step is presented. FTIR spectroscopy indicates that molecules with various
      terminal functionalities, such as alcohol, alkyl groups, and carboxylic acid, are
      grafted successfully onto the surface of silicon nanocrystals. The dispersibility
      of such SiQDs is clearly dependent on the terminal functional groups of the
      grafted molecules. In addition, the as-prepared SiQDs show excellent cell
      compatibility, photoluminescence properties, and stability, and their use as long
      term intracellular fluorescent probes is also demonstrated. It is envisaged that
      this facile and effective method for the stabilization and functionalization of
      SiQDs with tailored wetting and chemical properties will enable wide application
      of SiQDs in a number of areas.

PMID- 22623451
TI  - Prevalence of autoimmune inflammatory myopathy in the first nations population of
      Alberta, Canada.
AB  - OBJECTIVE: To estimate the population-based prevalence of autoimmune inflammatory
      myopathy (AIM) in Alberta, Canada, with a specific focus on rates in the First
      Nations population. METHODS: Physician billing claims and hospitalization data
      for the province of Alberta (1994-2007) were used to estimate the probability of
      having AIM (i.e., polymyositis or dermatomyositis) based on 3 case definitions. A
      latent class Bayesian hierarchical regression model was employed to account for
      the imperfect sensitivity and specificity of billing and hospitalization data in
      case ascertainment. We accounted for demographic factors of sex, age group, and
      location of residence (urban or rural) in estimating the prevalence rates within
      the First Nations and non-First Nations populations. RESULTS: The overall
      prevalence of AIM was 25.0 per 100,000 persons (95% credible interval [95% CrI]
      13.4-49.0) in the First Nations population and 33.8 (95% CrI 28.9-39.6) in the
      non-First Nations population. For both groups, prevalence was increased in women
      relative to men, rural women relative to urban women, and in those age >45 years.
      CONCLUSION: Unlike other rheumatic diseases such as rheumatoid arthritis,
      systemic lupus erythematosus, and systemic sclerosis, we did not detect an
      increased prevalence of AIM in Alberta's First Nations population relative to the
      non-First Nations population. Potential limitations include coding errors,
      underidentification of First Nations members, and recognized differences in
      access to care for the First Nations population.

PMID- 22623452
TI  - Life as it should be.

PMID- 22623453
TI  - Over-the-counter ibuprofen and acetaminophen in combination are superior to each
      agent alone in treating postoperative pain.

PMID- 22623454
TI  - Anterior restorations: Crowns, veneers, or direct composite--How do you decide?

PMID- 22623455
TI  - Conversion from fixed bridge to implant-supported restoration in the esthetic
      zone.

PMID- 22623456
TI  - Minimally invasive dentistry--A biomimetic approach.

PMID- 22623457
TI  - Dietary considerations for patients with dry mouth.
AB  - Dental caries is seen frequently in patients diagnosed with dry mouth.
      Nutritional counseling is important for the effective management of dry mouth and
      to arrest dental caries. With early intervention and proper individualized care,
      patients with dry mouth should be able to lead full, comfortable lives.

PMID- 22623458
TI  - A comparison of sports and energy drinks--Physiochemical properties and enamel
      dissolution.
AB  - The consumption of sports and energy drinks by children and adolescents has
      increased at an alarming rate in recent years. It is essential for dental
      professionals to be informed about the physiochemical properties of these drinks
      and their effects on enamel. The present study measured the fluoride levels, pH,
      and titratable acidity of multiple popular, commercially available brands of
      sports and energy drinks. Enamel dissolution was measured as weight loss using an
      in vitro multiple exposure model consisting of repeated short exposures to these
      drinks, alternating with exposure to artificial saliva. The relationship between
      enamel dissolution and fluoride levels, pH, and titratable acidity was also
      examined.  There was a statistically significant difference between the fluoride
      levels (p = 0.034) and pH (p = 0.04) of the sports and energy drinks studied. The
      titratable acidity of energy drinks (11.78) was found to be significantly higher
      than that of sports drinks (3.58) (p < 0.001). Five of the energy drinks (Red
      Bull Sugar Free, Monster Assault, Von Dutch, Rockstar, and 5-Hour Energy) were
      found to have the highest titratable acidity values among the brands studied.
      Enamel weight loss after exposure to energy drinks was significantly higher than
      it was after exposure to sports drinks. The effect of titratable acidity on
      enamel weight loss was found to vary inversely with the pH of the drinks.  The
      findings indicated that energy drinks have significantly higher titratable
      acidity and enamel dissolution associated with them than sports drinks. Enamel
      weight loss after exposure to energy drinks was more than two times higher than
      it was after exposure to sports drinks. Titratable acidity is a significant
      predictor of enamel dissolution, and its effect on enamel weight loss varies
      inversely with the pH of the drink. The data from the current study can be used
      to educate patients about the differences between sports and energy drinks and
      the effects of these drinks on tooth enamel.

PMID- 22623459
TI  - Antibiotics in dentistry: Bacteremia, antibiotic prophylaxis, and antibiotic
      misuse.
AB  - What is known regarding bacteremia? How effective is antibiotic prophylaxis for
      distant-site infections (late prosthetic joint infections and infective
      endocarditis)? Antibiotic resistance poses a growing danger to mankind. The
      misuse of antibiotics is a main cause of antibiotic resistance in bacteria. The
      author undertook a Medline search and a hand search of the literature regarding
      bacteremia, antibiotic prophylaxis for late prosthetic joint infections and
      infective endocarditis, antibiotic misuse, and antibiotic resistance. The
      findings indicate a clearer understanding of bacteremia emerging in the past 30
      years, which has led to recent changes in antibiotic prophylaxis regimens.
      Dentists should understand how bacteremia affects their at-risk patients, the
      rationale for antibiotic prophylaxis, and how antibiotic misuse poses a threat to
      all.

PMID- 22623460
TI  - Planning and implementation of community oral health programs for caries
      management in children.
AB  - Tooth decay or cavities (dental caries) can have a significant impact on
      children's quality of life, causing pain, infection, and other problems in the
      oral environment. Good oral health is a fundamental element of good general
      health for children, yet dental caries is still prevalent among children in many
      countries. Dental caries is well-understood, and effective prevention is an
      attainable goal. Dental professionals should actively engage with communities--in
      particular, the underprivileged--to identify dental caries problems and implement
      appropriate and effective community oral health programs (COHPs) to improve oral
      health and reduce oral health inequalities. This paper discusses COHPs as well as
      the steps involved in caries prevention for children. These steps cannot ensure
      the success of every COHP, but they are helpful for developing, integrating,
      expanding, and enhancing them. The effectiveness of COHPs for the prevention of
      caries in children varies from country to country, according to cultural, social,
      economic, and health care settings. Careful consideration of the local situation
      is required when selecting the elements of COHPs.

PMID- 22623461
TI  - Using clear aligner therapy to correct malocclusion with crowding and an open
      bite.
AB  - Clear aligner therapy (CAT) has been used successfully to correct minor spacing
      and crowding. It generally has not been indicated in more complicated
      malocclusions such as skeletal discrepancies and open bites; however, recent
      advances in technology and practitioner expertise now allow the use of CAT in
      these situations. This case report demonstrates the use of a CAT system
      (Invisalign) to correct a Class II malocclusion with crowding and an open bite
      tendency.

PMID- 22623462
TI  - Coronectomy with the diagnostic use of CBCT to aid in the prevention of
      iatrogenic damage to the inferior alveolar nerve.
AB  - This case report describes the treatment of a 27-year old man who presented to
      the oral and maxillofacial surgery division of a U.S. Navy recruit training
      center. Cone beam computed tomography determined the true three-dimensional
      relationship of the impacted teeth to the inferior alveolar neurovascular bundle.
      The tomograms aided in the surgical planning to decrease the probability of
      iatrogenic postoperative nerve disturbance.

PMID- 22623463
TI  - Bond strength evaluation of nanohybrid resin-based composite repair.
AB  - The objectives of this study were to determine the shear bond strength of a
      nanohybrid resin-based composite (RBC) when repaired with three different RBCs
      and to test the hypothesis that the type of composite used to repair, aging, and
      surface treatment prior to bonding affect shear bond strength on repairs of
      nanohybrid RBCs.  One hundred fifty cylinder specimens were built using a
      nanohybrid RBC (base cylinder). Half of these specimens were aged in distilled
      water for 24 hours at 37 degrees C, at which point the surface was roughened with
      abrasive discs, acid-etched, silanized, and adhesive-treated. The remaining 75
      specimens were not aged and did not receive surface treatment. Over each base
      cylinder, both aged and nonaged, a new cylinder was built (repair cylinder) from
      either nanohybrid RBC (n = 25), microhybrid RBC (n = 25), or microfilled RBC (n =
      25). All specimens were aged in distilled water for 24 hours at 37 degrees C and
      a shear bond strength test was performed.  Results indicated that aging and
      surface treatment significantly affected the shear bond strength of repaired
      samples (P < 0.0001). All aged groups showed lower shear bond strengths than
      their matching nonaged group. The type of RBC also affected the shear bond
      strength (P < 0.0001). Repair with either a nanohybrid RBC or a microhybrid RBC
      demonstrated the highest shear bond strength, while the lowest shear bond
      strength was observed when the cylinder was repaired with a microfilled RBC.

PMID- 22623464
TI  - Bilateral buccal mucosal lesions with whitish striated borders. Oral
      manifestations of systemic lupus erythematosus.

PMID- 22623465
TI  - Painful diffuse oral mucosal lesions. Pemphigus vulgaris.

PMID- 22623466
TI  - Effect of brushing with conventional versus whitening dentifrices on surface
      roughness and biofilm formation of dental ceramics.
AB  - The aim of this study was to evaluate the effect of conventional and whitening
      dentifrices on the weight loss, surface roughness, and early in situ biofilm
      formation on the surface of dental ceramics. Standardized feldspar ceramic
      specimens (Vita VM7 and Vita VM13) were submitted to the following experimental
      conditions: no brushing; brushing without a dentifrice; brushing with a
      conventional dentifrice; and brushing with a whitening dentifrice. A brushing
      machine was used to simulate brushing. The mass and surface roughness of all
      specimens from the test groups were evaluated prior to and after brushing. Ten
      participants used an oral device for eight hours to evaluate the biofilm formed
      in situ on the specimens. Scanning electron microscopy was used for qualitative
      and quantitative analysis of the biofilm. ANOVA and Tukey tests were used to
      analyze the results of weight loss, surface roughness, and presence of bacteria.
      A one-way Kruskal-Wallis test was used for bacterial colonization results.  For
      both ceramics, brushing with a whitening dentifrice resulted in weight loss that
      was significantly greater when compared to brushing without a dentifrice or with
      a conventional dentifrice. Increased surface roughness was noticed on VM13
      ceramic samples with both dentifrices, whereas only conventional dentifrice had a
      significant effect on the surface roughness of VM7 samples. For both VM7 and
      VM13, no difference was found between the experimental conditions with regard to
      the presence or number of bacteria. Cocci and short rods were the predominant
      microbial morphotypes. Granular or fibrillar acellular material partially covered
      the specimens. Brushing with a whitening dentifrice resulted in significant
      weight loss of ceramic restorations, while brushing with both conventional and
      whitening dentifrices can roughen ceramic surfaces. The increase in roughness was
      not clinically significant to contribute to increased biofilm formation.

PMID- 22623467
TI  - Cone beam computed tomography for diagnosis and treatment planning of
      supernumerary teeth.
AB  - Conventional radiographic images are frequently used to detect supernumerary
      teeth. However, recent developments in 3D imaging systems have enabled dentists
      to better visualize supernumerary teeth, with better contrast and more details.
      Cone beam computed tomography (CBCT) has improved diagnosis and treatment
      planning of patients with supernumerary teeth. The decision to use CBCT should be
      based on the diagnostic information required. This article presents three case
      reports of patients with supernumerary teeth to demonstrate the need for accurate
      diagnosis and treatment planning based on a comprehensive evaluation using CBCT.

PMID- 22623468
TI  - Effect of calcium hydroxide on the apical leakage of Resilon-filled root canals:
      An in vitro study.
AB  - Calcium hydroxide is used as an intracanal medication for root canal disinfection
      and to enhance periapical lesion healing. However, calcium hydroxide remnants can
      negatively affect the final apical seal of obturated canals. The current study
      investigated apical leakage in root canals filled with Resilon after calcium
      hydroxide treatment.  Seventy human maxillary central incisors were instrumented
      to a master apical file size of 40. Teeth were randomly divided into two
      experimental groups (A and B; n = 30) and two control groups (n = 5). Root canals
      in group A received a calcium hydroxide dressing, while those in group B received
      no intracanal medication. One week after treatment, all root canals were
      obturated with Resilon/Epiphany using lateral compaction. Groups A and B were
      randomly divided into subgroups A1, A2, B1, and B2 (n = 15). All subgroups were
      stored in an incubator at 37 degrees C and 100% humidity; subgroups A1 and B1
      were stored for one week, while subgroups A2 and B2 were stored for eight weeks.
      Dye penetration and clearing techniques were used to evaluate apical leakage.
      Data were analyzed using a Student t-test, with significance set at P < 0.05. 
      Observed apical leakage was significantly higher in subgroup A1 than in subgroups
      A2 and B1 and in subgroup A2 than in subgroup B2; no statistically significant
      difference was found between subgroups B1 and B2.  When used as an intracanal
      medication, calcium hydroxide increases the apical leakage of root canals filled
      with Resilon/Epiphany.

PMID- 22623469
TI  - Evaluation of in-office dental unit waterline testing.
AB  - In-office dental unit waterline (DUWL) testing systems are commercially available
      for monitoring DUWL bacteria. The current study compared Aquasafe, Petrifilm, and
      Heterotrophic Plate Count Sampler (HPCS) with R2A plating methodology, considered
      the gold standard for enumerating heterotrophic bacteria in potable water.
      Samples were collected from 20 dental units. Heterotrophic bacterial counts of
      <=500 CFUs/mL were used as the cut-off for assessing in-office testing compared
      to R2A laboratory plating. Validity was assessed using sensitivity and
      specificity, along with positive and negative predictive values. Results were
      also compared using concordance and kappa statistics. All in-office tests
      demonstrated 100% specificity and positive predictive values, while sensitivity
      and negative predictive values were low (Petrifilm, 57%/50%; HPCS, 50%/46%;
      Aquasafe, 21%/35%). Concordance and kappa values for agreement with R2A plating
      were as follows: Petrifilm 70% (kappa = 0.44), HPCS 65% (kappa = 0.38), and
      Aquasafe 45% (kappa = 0.14). In-office DUWL testing with Aquasafe, Petrifilm, and
      HPCS agreed poorly with R2A plating methodology and is not valid or reliable as a
      means of accurately monitoring bacterial density in DUWL. These in-office test
      systems should not be used for assessing compliance with the ADA and CDC standard
      for acceptable heterotrophic bacterial counts in DUWLs (<=500 CFUs/mL).

PMID- 22623470
TI  - Microtensile bond strength of a new silorane-based composite resin adhesive.
AB  - Filtek LS is a new composite resin restorative system with a unique, low
      shrinking, silorane-based monomer matrix. The current study was conducted to
      compare the durability of the bond to dentin of the new silorane-based bonding
      agent, Filtek Silorane System Adhesive, to the gold standard methacrylate-based
      bonding agent, Clearfil SE Bond. Extracted human molar teeth were sectioned to
      expose dentin. Either Filtek Silorane System Adhesive with Filtek LS composite or
      Clearfil SE Bond with Clearfil Majesty Posterior composite was applied to the
      dentin according to the manufacturer's instructions. The composites were placed
      incrementally and sectioned perpendicular to the composite-tooth interface to
      obtain rectangular beams. The beams were stored for 24 hours, 6 months, or 12
      months in distilled water and stressed in tension in a universal testing machine.
      Data were analyzed with a two-way ANOVA/Tukey test.  The 24-hour microtensile
      bond strengths were significantly greater than the 6- and 12-month bond
      strengths. Overall, there was no significant difference in the microtensile bond
      strength to dentin between the Filtek Silorane System Adhesive and the Clearfil
      SE Bond adhesive bonding agents. After one year of water storage, the new
      silorane-based composite resin bonding agent performed as well as the
      methacrylate-based composite resin bonding agent.

PMID- 22623471
TI  - Accuracy of cast posts and cores using a new investigative method.
AB  - Generally, two techniques are used to fabricate a cast post and core (CPC):
      direct and indirect. To date, research has made no clear indication as to a
      comparative level of accuracy between the techniques. Therefore, the purpose of
      the current study was to compare the accuracy of two techniques to produce CPCs
      for posterior teeth using a new method.  Nine endodontically treated human
      premolars were used for fabricating CPCs using the direct and indirect methods. A
      total of 18 CPCs were produced, two for each tooth, cast in high noble type IV
      gold. A silicone impression material was inserted into the root canals, followed
      by the CPCs. The remaining material in the space between the canal wall and the
      CPC was weighed using an electronic precision balance. By evaluating the weight
      of the silicon specimens, the accuracy and intimacy of fit were obtained. Since
      the number of samples was small, a Student t-test was used for statistical
      evaluation at a 90% confidence interval.  The CPCs obtained by using each method
      were independently examined by two clinicians for proper fit. Power analysis
      indicated that for a 90% confidence interval and 0.8 power value, nine specimens
      would be necessary to achieve a statistically meaningful test. The mean value for
      the weight of the nine specimens obtained using the direct method was 10.3 +/-
      2.6 mg, while the mean value for the corresponding specimens obtained using the
      indirect method was significantly smaller, 7.4 +/- 2.3 mg. The Student t-test
      value was P = 0.006.  The indirect method provided CPCs with a better fit and
      higher accuracy. The Student t-test demonstrated a significant difference between
      the direct and indirect procedures. The indirect method is a valuable technique
      for the dental practitioner when multiple posterior cast posts and cores are
      necessary or interocclusal space is limited.

PMID- 22623472
TI  - Minimally invasive intervention of acute trauma in the primary dentition:
      Successful five-year follow-up.
AB  - The main objectives of diagnosis and treatment of traumatic injuries affecting
      children in the primary dentition are pain management and prevention of damage to
      the developing tooth germ. Inappropriate approaches to treating dental trauma can
      cause more damage than the trauma itself; for this reason, minimal intervention
      presents a low risk of sequelae development in the permanent successor teeth.
      This case describes a five-year follow-up of acute trauma in the primary
      dentition. Conservative management with minimal intervention of the traumatized
      teeth was adopted. The traumatized teeth were followed until eruption of their
      permanent successors. The permanent teeth erupted in the correct order. The
      conservative management was a success and resulted in normal eruption of the
      permanent teeth with no sequelae.

PMID- 22623473
TI  - Crouzon syndrome--A case report.
AB  - Crouzon syndrome is a genetic disorder also known as branchial arch syndrome.
      Specifically, this syndrome affects the first branchial (or pharyngeal) arch, the
      precursor of the maxilla and mandible. Since the branchial arches are important
      developmental features in a growing embryo, disturbances in their development
      create lasting and widespread effects. Previously referred to as craniofacial
      dysostosis, the disorder is characterized by a number of clinical features; to
      date, it has no known single, initiating defect to account for all its
      characteristics. This article presents a case report of a 10-year-old boy with
      classical skeletal and soft tissue features of Crouzon syndrome.

PMID- 22623474
TI  - Neutral zone approach for the rehabilitation of a severely atrophic mandibular
      ridge: Case report.
AB  - Providing a complete denture for a patient with an atrophic mandibular ridge
      presents a unique challenge for dentists. Retention, stability, and support must
      be considered when fabricating and fitting a complete denture. This article
      highlights the use of the neutral zone technique for successful complete denture
      therapy in a patient with an atrophic mandibular ridge, with special emphasis on
      the role of coverage of genial tubercles for maximum prosthesis support and
      stability.

PMID- 22623475
TI  - Indirect resin-bonded fiber-reinforced composite anterior bridge: A case report.
AB  - The loss of anterior teeth can be painful for patients, both psychologically and
      socially. In recent years, fiber-reinforced composite resins (FRCs) have gained
      increasing acceptance in mainstream prosthodontics as viable alternatives to
      alloy-based restorations. A combination of good esthetics and fracture toughness
      validates their use in a diverse range of clinical applications. In this study, a
      bridge was constructed with hybrid composite resin placed around a resin
      impregnated, plasma-etched, polyalkene fiber bonded to the abutment tooth enamel
      using the acid-etch technique. This method of tooth replacement is viewed as a
      fast, simple, cost-effective means of replacing anterior teeth. The restoration
      remained intact, with no discoloration or deterioration at the recall visits.
      While definitive long-term data about their clinical performance is scarce, FRC
      prostheses appear to have a worthwhile role in the conservative treatment of
      short, edentulous spaces.

PMID- 22623476
TI  - Rehydration of a reattached fractured tooth fragment after prolonged dehydration.
AB  - Crown fractures of the anterior teeth are one of the most common outcomes of
      trauma to the orofacial region. The reattachment of dental fragments is a
      conservative treatment and should be considered a primary treatment choice in the
      restoration of anterior tooth fractures. This article presents a clinical
      technique for the restoration of a fractured maxillary lateral incisor by
      reattaching the tooth fragment that was kept in dry conditions for five days with
      the aid of adhesive dentistry. The esthetic compromise of white color (due to
      excessive dehydration of the segment) was reconciled after one month of service
      in the mouth by regaining the natural color by rehydration. The one-year clinical
      evaluation revealed a successful outcome for this technique, and the patient was
      pleased with the esthetic results of the conservative treatment modality.

PMID- 22623477
TI  - The "radiculous" maxillary first premolar: A rare anatomic variation.
AB  - Premolars have highly variable root canal morphology, but the presence of three
      roots is rare. This article describes the diagnosis and clinical management of a
      maxillary first premolar with three canals and three separate roots, with special
      reference to radiographic interpretation and access refinements. The authors'
      detection of multiple roots in all of the patient's premolars made this case
      unique. It is suggested that all general practitioners look for a similar
      anatomic variation in contralateral and opposing teeth as well.

PMID- 22623478
TI  - Pregnancy tumor mimicking a neoplasm--A case report.
AB  - Pregnancy brings about a complex series of physiological changes for women. A
      tumor-like gingival enlargement can occur during pregnancy. The size of the tumor
      generally increases gradually over a few months as the pregnancy progresses, then
      shrinks spontaneously after delivery. This case report describes a case of
      gingival swelling in a 26-year-old woman at five months of gestation. The lesion
      was not painful and grew very rapidly over a three-week period. The
      histopathological examination revealed granulation tissue with non-neoplastic
      proliferation of endothelial cells, suggestive of pregnancy tumor.

PMID- 22623480
TI  - Chromatographic lipid profiling of stress-exposed cells.
AB  - Lipidomics is an emerging field of science not only due to its integral part of
      cell biology and biophysics but also due to the key role of lipids in the
      modulation of membrane physical properties, signaling, and cell death regulation.
      The aim of this study was to characterize changes in N-palmitoyl ceramide
      concentration and in the global lipid profile in macrophages challenged by
      oxidized low-density lipoprotein and nutrient deprived hepatocytes. For this
      purpose, a quantitative targeted method based on gas chromatography-mass
      spectrometry for the determination of total N-palmitoyl ceramide concentrations
      in the cellular membranes of cells under stress was used. Ultrahigh-performance
      liquid chromatography-quadrupole-time of flight mass spectrometry was applied for
      the comprehensive profiling of lipids. In essence, we found that both models of
      cellular stress caused an increase in N-palmitoyl ceramide levels. In addition,
      increased levels of other ceramides were observed as well as up- and down
      regulation of several other lipid species.

PMID- 22623481
TI  - Conditioning intensity-dependent interaction between short-latency
      interhemispheric inhibition and short-latency afferent inhibition.
AB  - The relationship between sensory and transcallosal inputs into the motor cortex
      may be important in motor performance, but it has not been well studied,
      especially in humans. The aim of this study was to reveal this relationship by
      investigating the interaction between short-latency interhemispheric inhibition
      (SIHI) and short-latency afferent inhibition (SAI) in humans with transcranial
      magnetic stimulation. SIHI is the inhibition of the primary motor cortex (M1)
      elicited by contralateral M1 stimulation given ~10 ms before, and it reflects
      transcallosal inhibition. SAI is the inhibition of M1 elicited by contralateral
      median nerve stimulation preceding M1 stimulation by ~20 ms. In this
      investigation, we studied the intensity dependence of SIHI and SAI and the
      interaction between SIHI and SAI in various conditioning intensities. Subjects
      were 11 normal volunteers. The degree of effects was evaluated by comparing motor
      evoked potential sizes recorded from the first dorsal interosseous muscle between
      a certain condition and control condition. Both SIHI and SAI were potentiated by
      increment of the conditioning stimulus intensity and saturated at 1.4 times
      resting motor threshold for SIHI and 3 times sensory threshold for SAI. No
      significant interaction was observed when either of their intensities was
      subthreshold for the inhibition on its own. Only when both intensities were
      strong enough for their inhibition did the presence of one inhibition lessen the
      other one. On the basis of these findings, we conclude that interneurons
      mediating SIHI and SAI have mutual, direct, and inhibitory interaction in a
      conditioning intensity-dependent manner.

PMID- 22623482
TI  - Modulation of soleus H reflex by spinal DC stimulation in humans.
AB  - Transcranial direct current stimulation (tDCS) of the human motor cortex induces
      changes in excitability within cortical and spinal circuits that occur during and
      after the stimulation. Recently, transcutaneous spinal direct current stimulation
      (tsDCS) has been shown to modulate spinal conduction properties, as assessed by
      somatosensory-evoked potentials, and transynaptic properties of the spinal
      neurons, as tested by postactivation depression of the H reflex or by the RIII
      nociceptive component of the flexion reflex in the lower limb. To further explore
      tsDCS-induced plastic changes in spinal excitability, we examined, in a double
      blind crossover randomized study, the stimulus-response curves of the soleus H
      reflex before, during, at current offset and 15 min after anodal, cathodal, and
      sham tsDCS delivered at the Th11 level (2.5 mA, 15 min, 0.071 mA/cm(2), 0.064
      C/cm(2)) in 17 healthy subjects. Anodal tsDCS induced a progressive leftward
      shift of the recruitment curve of the soleus H reflex during the stimulation; the
      effects persisted for at least 15 min after current offset. In contrast, both
      cathodal and sham tsDCS had no significant effects. This exploratory study
      provides further evidence for the use of tsDCS as an expedient, noninvasive tool
      to induce long-lasting plastic changes in spinal circuitry. Increased spinal
      excitability after anodal tsDCS may have potential for spinal neuromodulation in
      patients with central nervous system lesions.

PMID- 22623483
TI  - Influence of the behavioral goal and environmental obstacles on rapid feedback
      responses.
AB  - The motor system must consider a variety of environmental factors when executing
      voluntary motor actions, such as the shape of the goal or the possible presence
      of intervening obstacles. It remains unknown whether rapid feedback responses to
      mechanical perturbations also consider these factors. Our first experiment
      quantified how feedback corrections were altered by target shape, which was
      either a circular dot or a bar. Unperturbed movements to each target were
      qualitatively similar on average but with greater dispersion of end point
      positions when reaching to the bar. On random trials, multijoint torque
      perturbations deviated the hand left or right. When reaching to a circular
      target, perturbations elicited corrective movements that were directed straight
      to the location of the target. In contrast, corrective movements when reaching to
      a bar were redirected to other locations along the bar axis. Our second
      experiment quantified whether the presence of obstacles could interfere with
      feedback corrections. We found that hand trajectories after the perturbations
      were altered to avoid obstacles in the environment. Importantly, changes in
      muscle activity reflecting the different target shapes (bar vs. dot) or the
      presence of obstacles were observed in as little as 70 ms. Such changes in motor
      responses were qualitatively consistent with simulations based on optimal
      feedback control. Taken together, these results highlight that long-latency motor
      responses consider spatial properties of the goal and environment.

PMID- 22623484
TI  - The state of somatosensory cortex during neuromodulation.
AB  - During behavioral quiescence, such as slow-wave sleep and anesthesia, the
      neocortex is in a deactivated state characterized by the presence of slow
      oscillations. During arousal, slow oscillations are absent and the neocortex is
      in an activated state that greatly impacts information processing.
      Neuromodulators acting in neocortex are believed to mediate these state changes,
      but the mechanisms are poorly understood. We investigated the actions of
      noradrenergic and cholinergic activation on slow oscillations, cellular
      excitability, and synaptic inputs in thalamocortical slices of somatosensory
      cortex. The results show that neuromodulation abolishes slow oscillations,
      dampens the excitability of principal cells, and rebalances excitatory and
      inhibitory synaptic inputs in thalamocortical-recipient layers IV-III. Sensory
      cortex is much more selective about the inputs that can drive it. The source of
      neuromodulation is critically important in determining this selectivity.
      Cholinergic activation suppresses the excitatory and inhibitory conductances
      driven by thalamocortical and intracortical inputs. Noradrenergic activation
      suppresses the excitatory conductance driven by intracortical inputs but not by
      thalamocortical inputs and enhances the inhibitory conductance driven by
      thalamocortical inputs but not by intracortical inputs. Thus noradrenergic
      activation emphasizes thalamocortical (sensory) inputs relative to intracortical
      inputs, while cholinergic activation suppresses both.

PMID- 22623485
TI  - Coactivation of different neurons within an isofrequency lamina of the inferior
      colliculus elicits enhanced auditory cortical activation.
AB  - The phenomenal success of the cochlear implant (CI) is attributed to its ability
      to provide sufficient temporal and spectral cues for speech understanding.
      Unfortunately, the CI is ineffective for those without a functional auditory
      nerve or an implantable cochlea required for CI implementation. As an
      alternative, our group developed and implanted in deaf patients a new auditory
      midbrain implant (AMI) to stimulate the central nucleus of the inferior
      colliculus (ICC). Although the AMI can provide frequency cues, it appears to
      insufficiently transmit temporal cues for speech understanding. The three
      dimensional ICC consists of two-dimensional isofrequency laminae. The single
      shank AMI only stimulates one site in any given ICC lamina and does not exhibit
      enhanced activity (i.e., louder percepts or lower thresholds) for repeated pulses
      on the same site with intervals <2-5 ms, as occurs for CI pulse or acoustic click
      stimulation. This enhanced activation, related to short-term temporal
      integration, is important for tracking the rapid temporal fluctuations of a
      speech signal. Therefore, we investigated the effects of coactivation of
      different regions within an ICC lamina on primary auditory cortex activity in
      ketamine-anesthetized guinea pigs. Interestingly, our findings reveal an
      enhancement mechanism for integrating converging inputs from an ICC lamina on a
      fast scale (<6-ms window) that is compromised when stimulating just a single ICC
      location. Coactivation of two ICC regions also reduces the strong and long-term
      (>100 ms) suppressive effects induced by repeated stimulation of just a single
      location. Improving AMI performance may require at least two shanks implanted
      along the tonotopic gradient of the ICC that enables coactivation of multiple
      regions along an ICC lamina with the appropriate interstimulus delays.

PMID- 22623486
TI  - Sensory reweighting of proprioceptive information of the left and right leg
      during human balance control.
AB  - To keep balance, information from different sensory systems is integrated to
      generate corrective torques. Current literature suggests that this information is
      combined according to the sensory reweighting hypothesis, i.e., more reliable
      information is weighted more strongly than less reliable information. In this
      approach, no distinction has been made between the contributions of both legs. In
      this study, we investigated how proprioceptive information from both legs is
      combined to maintain upright stance. Healthy subjects maintained balance with
      eyes closed while proprioceptive information of each leg was perturbed
      independently by continuous rotations of the support surfaces (SS) and the human
      body by platform translation. Two conditions were tested: perturbation amplitude
      of one SS was increased over trials while the other SS 1) did not move or 2) was
      perturbed with constant amplitude. With the use of system identification
      techniques, the response of the ankle torques to the perturbation amplitudes
      (i.e., the torque sensitivity functions) was determined and how much each leg
      contributed to stabilize stance (i.e., stabilizing mechanisms) was estimated.
      Increased amplitude of one SS resulted in a decreased torque sensitivity. The
      torque sensitivity to the constant perturbed SS showed no significant
      differences. The properties of the stabilizing mechanisms remained constant
      during perturbations of each SS. This study demonstrates that proprioceptive
      information from each leg is weighted independently and that the weight decreases
      with perturbation amplitude. Weighting of proprioceptive information of one leg
      has no influence on the weight of the proprioceptive information of the other
      leg. According to the sensory reweighting hypothesis, vestibular information must
      be up-weighted, because closing the eyes eliminates visual information.

PMID- 22623487
TI  - Presynaptic modulation by somatostatin in the rat neostriatum is altered in a
      model of parkinsonism.
AB  - Somatostatin (SST) is a peptide synthesized and released by a class of
      neostriatal local GABAergic interneurons, which, to some extent, are in charge of
      the feedforward inhibitory circuit. Spiny projection neurons (SPNs) make synapses
      with each other via their local axon collaterals, shaping the feedback inhibitory
      circuit. Both inhibitory circuits, feedforward and feedback, are related through
      SST, which, being released by interneurons, presynaptically inhibits connections
      among SPNs. Here, we studied SST presynaptic modulation of synapses among SPNs in
      the 6-hydroxydopamine (6-OHDA) rodent model of parkinsonism. We performed
      antidromic field stimulation from the external globus pallidus and whole cell
      voltage-clamp recordings of antidromically evoked inhibitory postsynaptic
      currents (IPSCs) among SPNs. SST presynaptically reduced IPSCs by ~34% in all
      control synapses tested. However, after striatal dopamine deprivation, three
      changes became evident. First, it was harder to evoke feedback inhibition.
      Second, presynaptic inhibition of some SPNs connections was larger than in
      controls: 57% reduction in ~53% of evoked IPSCs. Presynaptic inhibition was
      recorded from direct pathway neurons (direct SPNs). Finally, SST also induced
      presynaptic facilitation in some SPNs connections, with 82% enhancement in ~43%
      of evoked IPSCs. Presynaptic facilitation was recorded from indirect pathway
      neurons (indirect SPNs). Both inhibition and facilitation were accompanied by
      corresponding changes in the paired pulse ratio. It was demonstrated that after
      dopamine deprivation, SST modulation is altered in surviving feedback inhibitory
      synapses. It may underlie a homeostatic mechanism trying to compensate for the
      excitability imbalance between direct and indirect basal ganglia pathways found
      during parkinsonism.

PMID- 22623489
TI  - Fine-grained analysis of shared neural circuits between perceived and observed
      pain: implications for the study of empathy for pain.
AB  - Feeling pain and seeing it in others activates largely overlapping neural
      substrates. A recent study (Corradi-Dell'Acqua C, Hofstetter C, Vuilleumier P. J
      Neurosci 31: 17996-18006, 2011) for the first time raises the question of whether
      shared neural activations specifically code pain-related contents or merely their
      negative-aversive implication. The authors conclude that mid-insula and mid
      cingulate share information specific to the presence of pain, whereas anterior
      insula shares information about its aversive content. We suggest that, together
      with valence and arousal, the control of saliency and threat may have an
      important heuristic potential in the study of empathy for pain.

PMID- 22623488
TI  - Split-belt walking: adaptation differences between young and older adults.
AB  - Human walking is highly adaptable, which allows us to walk under different
      circumstances. With aging, the probability of falling increases, which may
      partially be due to a decreased ability of older adults to adapt the gait pattern
      to the needs of the environment. The literature on visuomotor adaptations during
      reaching suggests, however, that older adults have little problems in adapting
      their motor behavior. Nevertheless, it may be that adaptation during a more
      complex task like gait is compromised by aging. In this study, we investigated
      the ability of young (n = 8) and older (n = 12) adults to adapt their gait
      pattern to novel constraints with a split-belt paradigm. Findings revealed that
      older adults adapted less and more slowly to split-belt walking and showed fewer
      aftereffects than young adults. While young adults showed a fast adjustment of
      the relative time spent in swing for each leg older adults failed to do so, but
      instead they were very fast in manipulating swing speed differences between the
      two legs. We suggest that these changes in adaptability of gait due to aging stem
      from a mild degradation of cortico-cerebellar pathways (reduced adaptability) and
      cerebral structures (decreased ability to change gait cycle timing). However, an
      alternative interpretation may be that the observed reduced adaptation is a
      compensatory strategy in view of the instability induced by the split-belt
      paradigm.

PMID- 22623490
TI  - gamma Oscillations are involved in the sensorimotor transformation of pain.
AB  - Pain signals threat and initiates motor responses to avoid harm. The
      transformation of pain into a motor response is thus an essential part of pain.
      Here, we investigated the neural mechanisms subserving the sensorimotor
      transformation of pain at the cortical level by using electroencephalography. In
      a simple reaction time experiment, brief painful stimuli were delivered to the
      left hand of healthy human subjects who responded with button presses of the
      right hand. The results show that the simple reaction time task was associated
      with neuronal responses at delta/theta, alpha/beta, and gamma frequencies. The
      analysis of the relationship between neuronal activity and response speed
      revealed that gamma oscillations, which were temporally coupled to the painful
      stimuli, but not temporally coupled to the motor response, predicted reaction
      times. Lateralization of gamma oscillations indicates that they originate from
      motor areas rather than from sensory areas. We conclude that gamma oscillations
      are involved in the sensorimotor transformation of pain whose efficiency they
      reflect. We hypothesize that the relationship between stimulus-locked gamma
      oscillations and reaction times reflects a direct thalamo-motor route of
      nociceptive information that is central to the biological function of pain.

PMID- 22623491
TI  - Multijoint error compensation mediates unstable object control.
AB  - A key feature of skilled object control is the ability to correct performance
      errors. This process is not straightforward for unstable objects (e.g., inverted
      pendulum or "stick" balancing) because the mechanics of the object are sensitive
      to small control errors, which can lead to rapid performance changes. In this
      study, we have characterized joint recruitment and coordination processes in an
      unstable object control task. Our objective was to determine whether skill
      acquisition involves changes in the recruitment of individual joints or
      distributed error compensation. To address this problem, we monitored stick
      balancing performance across four experimental sessions. We confirmed that
      subjects learned the task by showing an increase in the stability and length of
      balancing trials across training sessions. We demonstrated that motor learning
      led to the development of a multijoint error compensation strategy such that
      after training, subjects preferentially constrained joint angle variance that
      jeopardized task performance. The selective constraint of destabilizing joint
      angle variance was an important metric of motor learning. Finally, we performed a
      combined uncontrolled manifold-permutation analysis to ensure the variance
      structure was not confounded by differences in the variance of individual joint
      angles. We showed that reliance on multijoint error compensation increased,
      whereas individual joint variation (primarily at the wrist joint) decreased
      systematically with training. We propose a learning mechanism that is based on
      the accurate estimation of sensory states.

PMID- 22623492
TI  - Genome comparison of barley and maize smut fungi reveals targeted loss of RNA
      silencing components and species-specific presence of transposable elements.
AB  - Ustilago hordei is a biotrophic parasite of barley (Hordeum vulgare). After
      seedling infection, the fungus persists in the plant until head emergence when
      fungal spores develop and are released from sori formed at kernel positions. The
      26.1-Mb U. hordei genome contains 7113 protein encoding genes with high synteny
      to the smaller genomes of the related, maize-infecting smut fungi Ustilago maydis
      and Sporisorium reilianum but has a larger repeat content that affected genome
      evolution at important loci, including mating-type and effector loci. The U.
      hordei genome encodes components involved in RNA interference and heterochromatin
      formation, normally involved in genome defense, that are lacking in the U. maydis
      genome due to clean excision events. These excision events were possibly a result
      of former presence of repetitive DNA and of an efficient homologous recombination
      system in U. maydis. We found evidence of repeat-induced point mutations in the
      genome of U. hordei, indicating that smut fungi use different strategies to
      counteract the deleterious effects of repetitive DNA. The complement of U. hordei
      effector genes is comparable to the other two smuts but reveals differences in
      family expansion and clustering. The availability of the genome sequence will
      facilitate the identification of genes responsible for virulence and evolution of
      smut fungi on their respective hosts.

PMID- 22623494
TI  - Fatty acid phytyl ester synthesis in chloroplasts of Arabidopsis.
AB  - During stress or senescence, thylakoid membranes in chloroplasts are
      disintegrated, and chlorophyll and galactolipid are broken down, resulting in the
      accumulation of toxic intermediates, i.e., tetrapyrroles, free phytol, and free
      fatty acids. Chlorophyll degradation has been studied in detail, but the
      catabolic pathways for phytol and fatty acids remain unclear. A large proportion
      of phytol and fatty acids is converted into fatty acid phytyl esters and
      triacylglycerol during stress or senescence in chloroplasts. We isolated two
      genes (PHYTYL ESTER SYNTHASE1 [PES1] and PES2) of the
      esterase/lipase/thioesterase family of acyltransferases from Arabidopsis thaliana
      that are involved in fatty acid phytyl ester synthesis in chloroplasts. The two
      proteins are highly expressed during senescence and nitrogen deprivation.
      Heterologous expression in yeast revealed that PES1 and PES2 have phytyl ester
      synthesis and diacylglycerol acyltransferase activities. The enzymes show broad
      substrate specificities and can employ acyl-CoAs, acyl carrier proteins, and
      galactolipids as acyl donors. Double mutant plants (pes1 pes2) grow normally but
      show reduced phytyl ester and triacylglycerol accumulation. These results
      demonstrate that PES1 and PES2 are involved in the deposition of free phytol and
      free fatty acids in the form of phytyl esters in chloroplasts, a process involved
      in maintaining the integrity of the photosynthetic membrane during abiotic stress
      and senescence.

PMID- 22623495
TI  - Screening a cDNA library for protein-protein interactions directly in planta.
AB  - Screening cDNA libraries for genes encoding proteins that interact with a bait
      protein is usually performed in yeast. However, subcellular compartmentation and
      protein modification may differ in yeast and plant cells, resulting in
      misidentification of protein partners. We used bimolecular fluorescence
      complementation technology to screen a plant cDNA library against a bait protein
      directly in plants. As proof of concept, we used the N-terminal fragment of
      yellow fluorescent protein- or nVenus-tagged Agrobacterium tumefaciens VirE2 and
      VirD2 proteins and the C-terminal extension (CTE) domain of Arabidopsis thaliana
      telomerase reverse transcriptase as baits to screen an Arabidopsis cDNA library
      encoding proteins tagged with the C-terminal fragment of yellow fluorescent
      protein. A library of colonies representing ~2 * 10(5) cDNAs was arrayed in 384
      well plates. DNA was isolated from pools of 10 plates, individual plates, and
      individual rows and columns of the plates. Sequential screening of subsets of
      cDNAs in Arabidopsis leaf or tobacco (Nicotiana tabacum) Bright Yellow-2
      protoplasts identified single cDNA clones encoding proteins that interact with
      either, or both, of the Agrobacterium bait proteins, or with CTE. T-DNA
      insertions in the genes represented by some cDNAs revealed five novel Arabidopsis
      proteins important for Agrobacterium-mediated plant transformation. We also used
      this cDNA library to confirm VirE2-interacting proteins in orchid (Phalaenopsis
      amabilis) flowers. Thus, this technology can be applied to several plant species.

PMID- 22623496
TI  - Photosynthetic quantum yield dynamics: from photosystems to leaves.
AB  - The mechanisms underlying the wavelength dependence of the quantum yield for
      CO(2) fixation (alpha) and its acclimation to the growth-light spectrum are
      quantitatively addressed, combining in vivo physiological and in vitro molecular
      methods. Cucumber (Cucumis sativus) was grown under an artificial sunlight
      spectrum, shade light spectrum, and blue light, and the quantum yield for
      photosystem I (PSI) and photosystem II (PSII) electron transport and alpha were
      simultaneously measured in vivo at 20 different wavelengths. The wavelength
      dependence of the photosystem excitation balance was calculated from both these
      in vivo data and in vitro from the photosystem composition and spectroscopic
      properties. Measuring wavelengths overexciting PSI produced a higher alpha for
      leaves grown under the shade light spectrum (i.e., PSI light), whereas
      wavelengths overexciting PSII produced a higher alpha for the sun and blue
      leaves. The shade spectrum produced the lowest PSI:PSII ratio. The photosystem
      excitation balance calculated from both in vivo and in vitro data was
      substantially similar and was shown to determine alpha at those wavelengths where
      absorption by carotenoids and nonphotosynthetic pigments is insignificant (i.e.,
      >580 nm). We show quantitatively that leaves acclimate their photosystem
      composition to their growth light spectrum and how this changes the wavelength
      dependence of the photosystem excitation balance and quantum yield for CO(2)
      fixation. This also proves that combining different wavelengths can enhance
      quantum yields substantially.

PMID- 22623499
TI  - Micellar electrokinetic chromatography systems for the separation of mixtures of
      charged and uncharged compounds.
AB  - In this study, the migration behavior of charged and uncharged analytes was
      investigated under different conditions. Effective mobilities - electrophoretic
      mobilities under the influence of micelles - of cations, anions, and neutrals
      were measured at neutral, basic, and acidic pH (7.5, 11, and 2.2) using
      background electrolytes containing different sodium dodecyl sulfate (SDS)
      concentrations (0-90 mM) and acetonitrile (ACN) proportions (0-75%). SDS
      concentration and ACN proportion were found to have a tremendous effect on the
      effective mobilities and migration order of the model compounds. Although the SDS
      micelles preferably interact with neutrals and cations, hydrophobic bonds can
      also occur with anions. Cations, anions, and neutrals having rather different
      migration behaviors, it is possible to considerably enhance the selectivity of
      the method by adjusting properly the SDS concentration and the ACN proportion.
      These observations confirm the interest of using micellar electrokinetic
      chromatography not only for the separation of neutral substances but also to
      analyze charged compounds.

PMID- 22623500
TI  - Asteroid hyalosis of the vitreous humor: an uncommon finding.

PMID- 22623501
TI  - Plasmonic trapping with a gold nanopillar.
AB  - An improved ability to manipulate nanoscale objects could spur the field of
      nanotechnology. Optical tweezers offer the compelling advantage that manipulation
      is performed in a non-invasive manner. However, traditional optical tweezers
      based on laser beams focused with microscope lenses face limitations due to the
      diffraction limit, which states that conventional lenses can focus light to spots
      no smaller than roughly half the wavelength. This has motivated recent work on
      optical trapping based on the sub-wavelength field distributions of surface
      plasmon nanostructures. This approach offers the benefits of higher precision and
      resolution, and the possibility of large-scale parallelization. Herein, we
      discuss the fundamentals of optical manipulation using surface plasmon resonance
      structures. We describe two important issues in plasmonic trapping: optical
      design and thermal management strategies. Finally, we describe a surface plasmon
      nanostructure, consisting of a gold nanopillar that takes these issues into
      consideration. It is shown to enable the trapping and rotation (manual and
      passive) of nanoparticles. Methods by which this concept can be extended are
      discussed.

PMID- 22623502
TI  - Separation and determination of resibufogenin and cinobufagin in Chansu using
      reversed-phase liquid chromatography with gamma-cyclodextrin as mobile-phase
      modifier.
AB  - A simple, accurate, sensitive, and robust reversed-phase high-performance liquid
      chromatography (HPLC) method employing cyclodextrins as mobile phase additives
      has been developed in order to separate and determine resibufogenin and
      cinobufagin. Various factors affecting the separation for them, such as the
      nature of cyclodextrins, organic solvent, the concentration of gamma
      cyclodextrin, and temperature, were systematically studied. gamma-cyclodextrin,
      as an effective mobile phase additive, can markedly improve the separation for
      resibufogenin and cinobufagin. The role of gamma-cyclodextrin in the developed
      HPLC method is attributed to the formation of the inclusion complex between
      resibufogenin (or cinobufagin) and gamma-cyclodextrin. So, the apparent formation
      constant (K(f) ) of the resibufogenin (or cinobufagin)/gamma-cyclodextrin
      inclusion complex and the thermodynamic parameters of the inclusion process also
      were investigated. Resibufogenin (or cinobufagin) forms the 1:1 inclusion
      complexes with gamma-cyclodextrin, and the resibufogenin/gamma-cyclodextrin
      complex is more stable than the cinobufagin/gamma-cyclodextrin complex. The K(f) 
      values of resibufogenin and cinobufagin decrease with the increase of the
      temperature. The thermodynamic parameters of the inclusion reveal that the
      inclusion process between resibufogenin (or cinobufagin) and gamma-cyclodextrin
      is spontaneous, exothermic, and enthalpically driven. Finally, the optimized
      method was successfully applied to separate and determine of resibufogenin and
      cinobufagin in the different Chansu (Bufonis venenum) samples.

PMID- 22623503
TI  - Phoenix rising: gene therapy makes a comeback.
AB  - Despite the first application of gene therapy in 1990, gene therapy has until
      recently failed to meet the huge expectations set forth by researchers,
      clinicians, and patients, thus dampening enthusiasm for an imminent cure for many
      life-threatening genetic diseases. Nonetheless, in recent years we have witnessed
      a strong comeback for gene therapy, with clinical successes in young and adult
      subjects suffering from inherited forms of blindness or from X-linked severe
      combined immunodeficiency disease. In this review, various gene therapy vectors
      progressing into clinical development and pivotal advances in gene therapy trials
      will be discussed.

PMID- 22623504
TI  - Analysis of reference gene expression for real-time PCR based on relative
      quantitation and dual spike-in strategy in the silkworm Bombyx mori.
AB  - In general, for real-time quantitative polymerase chain reaction (qPCR),
      normalization strategies use a reference gene as a control and to avoid the
      introduction of experimental errors expression of this gene should not vary in
      response to changing conditions. However, the expression of many reference genes
      has been reported to vary considerably and, without appropriate normalization,
      the expression profile of a target gene can be misinterpreted. In this study, the
      expression levels of seven commonly used reference genes (ACT, GAPDH, 28srRNA,
      RPL3, alpha-tubulin, UBC, and TBP) were detected at different development time
      points and in response to treatment with 20-hydroxyecdysone (20E) and with rutin.
      The expression stability was analyzed using geNorm and NormFinder software.
      Significant variations were found among normal tissues and between experimentally
      treated tissues. The dual spike-in strategy also revealed significant variations
      of the expression levels of the reference genes among normal tissues and between
      experimentally treated tissues. Glutathione-S-transferase sigma 1 (GSTs1), which
      has a high expression level in fat body and is related to the mechanism of
      resistance, was used as a target gene to validate the feasibility and difference
      of these two approaches.

PMID- 22623505
TI  - Non-Hodgkin lymphoma in early life.

PMID- 22623506
TI  - Perinatal and family risk factors for non-Hodgkin lymphoma in early life: a
      Swedish national cohort study.
AB  - BACKGROUND: The incidence of non-Hodgkin lymphoma (NHL) in early life has
      increased in recent decades, but the relevant risk factors remain largely
      unknown. We examined perinatal and family risk factors for NHL in childhood
      through young adulthood. METHODS: We conducted a national cohort study of 3 571
      574 individuals born in Sweden in 1973-2008 who were followed for incidence of
      NHL through 2009 (ages 0-37 years). Detailed information on perinatal and family
      characteristics and NHL diagnoses were obtained from national birth and cancer
      registries. Cox proportional hazards regression was used to estimate hazard
      ratios (HRs) and 95% confidence intervals (CIs) for the association between
      perinatal and family variables and NHL; P values are from two-sided tests.
      RESULTS: There were 936 NHL case patients identified in 66.3 million person-years
      of follow-up. Independent risk factors for NHL included family history of NHL in
      either a sibling (adjusted HR = 9.84; 95% CI = 2.46 to 39.41; P = .001) or parent
      (adjusted HR = 2.36; 95% CI = 1.27 to 4.38; P = .007); high fetal growth (for >=
      2 SDs relative to 0 to <1 SD from the mean: adjusted HR = 1.64; 95% CI = 1.19 to
      2.25; P = .002); older maternal age (adjusted HR for each 5-year increment =
      1.11; 95% CI = 1.04 to 1.19; P (trend) = .004); low birth order (adjusted HR for
      each increment of one birth = 0.91; 95% CI = 0.84 to 0.99; P (trend) = .02); and
      male sex (adjusted HR = 1.58; 95% CI = 1.38 to 1.80; P < .001). Male sex was
      associated with onset of NHL before 15 years of age but not with later-onset NHL,
      whereas the other risk factors did not vary by age at diagnosis. No association
      was found between gestational age at birth, twinning, paternal age, or parental
      education and NHL. CONCLUSION: In this large national cohort study, family
      history of NHL, high fetal growth, older maternal age, low birth order, and male
      sex were independent risk factors for NHL in early life.

PMID- 22623507
TI  - Trauma and sex surveys meet minimal risk standards: implications for
      institutional review boards.
AB  - Institutional review boards assume that questionnaires asking about "sensitive"
      topics (e.g., trauma and sex) pose more risk to respondents than seemingly
      innocuous measures (e.g., cognitive tests). We tested this assumption by asking
      504 undergraduates to answer either surveys on trauma and sex or measures of
      cognitive ability, such as tests of vocabulary and abstract reasoning.
      Participants rated their positive and negative emotional reactions and the
      perceived benefits and mental costs of participating; they also compared their
      study-related distress with the distress arising from normal life stressors.
      Participants who completed trauma and sex surveys, relative to participants who
      completed cognitive measures, rated the study as resulting in higher positive
      affect and as having greater perceived benefits and fewer mental costs. Although
      participants who completed trauma and sex surveys reported slightly higher levels
      of negative emotion than did participants who completed cognitive measures,
      averages were very low for both groups, and outliers were rare. All participants
      rated each normal life stressor as more distressing than participating in the
      study. These results suggest that trauma and sex surveys pose minimal risk.

PMID- 22623508
TI  - Saved by a log: how do humans perform hybrid visual and memory search?
AB  - Could you find 1 of your 1,000 Facebook friends in a crowd of 100? Even at a rate
      of 25 ms per comparison, determining that no friends were in the crowd would take
      more than 40 min if memory and visual search interacted linearly. In the
      experiment reported here, observers memorized pictures of 1 to 100 targets and
      then searched for any of these targets in visual displays of 1 to 16 objects.
      Response times varied linearly with visual set size but logarithmically with
      memory set size. Data from memory set sizes of 1 through 16 accurately predicted
      response times for different observers holding 100 objects in memory. The results
      would be consistent with a binary coding of visual objects in memory and are
      relevant to applied searches in which experts look for any of many items of
      interest (e.g., a radiologist running through a mental checklist of what might be
      wrong in a car-crash victim or an airport screener looking for any of a list of
      prohibited items in a carry-on bag).

PMID- 22623509
TI  - Face structure predicts cooperation: men with wider faces are more generous to
      their in-group when out-group competition is salient.
AB  - Male facial width-to-height ratio appears to correlate with antisocial
      tendencies, such as aggression, exploitation, cheating, and deception. We present
      evidence that male facial width-to-height ratio is also associated with a
      stereotypically male prosocial tendency: to increase cooperation with other in
      group members during intergroup competition. We found that men who had wider
      faces, compared with men who had narrower faces, showed more self-sacrificing
      cooperation to help their group members when there was competition with another
      group. We propose that this finding makes sense given the evolutionary functions
      of social helpfulness and aggression.

PMID- 22623511
TI  - Detecting nasty data with simple plots of complex models: comment on Brandt
      (2011).

PMID- 22623512
TI  - Urine cytomorphology of micropapillary urothelial carcinoma.
AB  - Micropapillary urothelial carcinoma (MPUC) is a rare subtype of urothelial
      carcinoma (UC) with an aggressive clinical course. The cytomorphologic features
      of MPUC in urine cytology have not been well described. In this study, 23 urine
      specimens (11 voided urines and 12 bladder washings) from 23 patients with MPUC
      on follow-up surgical material and 28 specimens (14voided urines and 14 bladder
      washings) from 28 patients with high-grade UCs (HGUC) were retrieved. Cytologic
      features (nuclear grade, cytoplasmic characteristics), architectural features
      (single cell pattern, true papillary structures, flat sheets/nests, three
      dimensional clusters, micropapillary (inside-out, acinar-like, or cauliflower
      with nuclei located peripherally)), and necrosis were evaluated. Clinical follow
      up was obtained by chart review. Two findings, micropapillae and cytoplasmic
      vacuoles, were seen more frequently in MPUC compared to HGUC, 81.0% vs. 14.3%,
      and 57.1% vs. 14.3%, respectively. The combination of these two findings had a
      sensitivity of 78%, a specificity of 86%, a positive predictive value of 82%, and
      a negative predictive value of 83% for the diagnosis of MPUC on subsequent
      biopsy. MPUC and HGUC can both exhibit a single cell pattern, papillary
      structures, flat sheets/nests, three dimensional clusters, high-nuclear grade,
      and necrosis, thus these findings are not useful in distinguishing these
      entities. Chart review revealed that patients with MPUC had a higher rate of
      metastasis to lymph nodes and distant organs than HGUC, 57% vs. 4%. Therefore,
      the findings of cytoplasmic vacuoles and micropapillary structures in UC from a
      urine cytology specimen are associated with MPUC on subsequent biopsy.

PMID- 22623513
TI  - Nano-flow multidimensional liquid chromatography platform integrated with
      combination of protein and peptide separation for proteome analysis.
AB  - An integrated multidimensional nano-flow liquid chromatography platform with the
      combination of protein and peptide separation via online digestion by an
      immobilized enzymatic reactor was established, and successfully applied for
      proteome analysis. By this platform, proteins were first separated by a weak
      anion and weak cation mixed-bed microcolumn under a series of salt steps, online
      digested by a trypsin immobilized enzymatic reactor, digests trapped and desalted
      by a C18 precolumn, separated by nano-reversed phase liquid chromatography, and
      finally identified by electrospray ionization-MS/MS. To evaluate the performance
      of such a platform, Escherichia coli whole cell lysate proteins were analyzed.
      Compared with the results obtained by shotgun approach, the identified protein
      number was increased by 6%, with the consumed time decreased from 38 to 14 h. We
      also compared with integrate platform based on micro-HPLC, and the required
      sample amount was decreased to 8 MUg. These results demonstrated that such an
      integrated approach would be an attractive alternative to commonly applied
      approaches for proteome research.

PMID- 22623514
TI  - Follicular lymphoma transformed to "double-hit" B lymphoblastic lymphoma
      presenting in the peritoneal fluid.
AB  - Lymphomas showing both MYC/8q24 rearrangement and IGH@BCL2/t(14;18)(q32;q21),
      also referred to as "double-hit" or "dual-hit" lymphomas (DHL) are rare B-cell
      malignancies with a germinal center B-cell immunophenotype and heterogeneous
      cytologic and histologic features. Such lymphomas may arise de novo or through
      transformation of follicular lymphomas and are classified either as "B-cell
      lymphoma, unclassifiable, with features intermediate between diffuse large B-cell
      lymphoma (DLBCL) and Burkitt lymphoma (BL)" (most commonly), DLBCL, or, rarely,
      as B-lymphoblastic lymphoma. We report a case of B-lymphobastic lymphoma arising
      through transformation of follicular lymphoma diagnosed on peritoneal fluid
      cytology, flow cytometry, and cytogenetic studies in a 53-year-old man who
      presented with abdominal pain, shortness of breath, night sweats, extensive
      lymphadenopathy, pleural effusion, and ascites. Cytologic examination of the
      ascitic fluid showed two distinct populations of neoplastic lymphoid cells, a
      predominant population of larger cells with fine powdery ("blastic") chromatin,
      visible to prominent nucleoli and occasional small cytoplasmic vacuoles and a
      less numerous population of smaller cells with centrocytic morphology. Flow
      cytometry also showed two distinct monotypic B-cell populations, both expressing
      CD10, and TdT-positivity was demonstrated immunohistochemically. Fluorescence in
      situ hybridization (FISH) demonstrated both MYC rearrangement and IGH/BCL2 gene
      fusion and cytogenetic analysis showed a complex karyotype including both
      t(14;18)(q32;q21) and t(8;22)(q24.1;q11.2). Since DHL pursue an aggressive
      clinical course, respond poorly to therapy, and have a poor outcome, it is
      important to suspect the diagnosis when encountering neoplastic lymphoid cells
      that are difficult to classify in effusion cytology specimens and to order the
      appropriate immunophenotyping and cytogenetic studies.

PMID- 22623515
TI  - Global gene expression profiling of proliferative phase endometrium reveals
      distinct functional subdivisions.
AB  - The human endometrium follows a predictable pattern of development during the
      proliferative phase. Endometrial thickness increases after day 3 and then
      plateaus at days 9 to 10 of the menstrual cycle despite continued high serum
      levels of estrogen. We hypothesized that proliferative phase endometrium
      undergoes more than simple estrogen responsive growth, rather it is characterized
      by complex time-dependent functional activities reflected in differential gene
      expression. Nine endometrial RNA samples from healthy participants were subjected
      to microarray analysis and 15 samples were used for quantitative real-time
      polymerase chain reaction. The samples were divided into early, mid, or late
      proliferative phase. The early proliferative phase showed higher expression of
      genes including transforming growth factor beta2, chemokine (C-C motif) ligand 18
      (CCL18), and metallothionein 2A. The mid-proliferative phase was characterized by
      higher expression of heat shock proteins and implantation-associated genes
      including Indian hedgehog, secreted frizzled protein 4, and progesterone
      receptor. In the late proliferative phase, we identified increased angiotensin II
      receptor, type 2 and large decrease in expression of genes related to natural
      killer (NK) cell function. We demonstrate a unique gene expression signature at
      distinct time points within the proliferative phase. The early proliferative
      phase is characterized by tissue remodeling, angiogenesis, and modulation of
      inflammation; the mid-proliferative phase is characterized not only by
      proliferation in response to estrogens but also marks the onset of expression of
      genes required for endometrial receptivity and a dampening of estrogen
      responsiveness. In the late proliferative phase, changes in immune function and
      NK cells predominate. The proliferative phase is not simply a uniform period of
      estrogen responsive endometrial growth that can be considered as a single
      experimental time point when evaluating endometrial development; rather the
      proliferative phase is complex with differing functions and patterns of gene
      expression.

PMID- 22623516
TI  - The Arabidopsis ortholog of rice DWARF27 acts upstream of MAX1 in the control of
      plant development by strigolactones.
AB  - Strigolactones (SLs) are carotenoid-derived plant hormones that regulate shoot
      branching, secondary growth, root development, and responses to soil phosphate.
      In Arabidopsis (Arabidopsis thaliana), SL biosynthesis requires the sequential
      action of two carotenoid cleavage dioxygenases, MORE AXILLARY GROWTH3 (MAX3) and
      MAX4, followed by a cytochrome P450, MAX1. In rice (Oryza sativa), the plastid
      localized protein DWARF27 (OsD27) is also necessary for SL biosynthesis, but the
      equivalent gene in Arabidopsis has not been identified. Here, we use phylogenetic
      analysis of D27-like sequences from photosynthetic organisms to identify AtD27,
      the likely Arabidopsis ortholog of OsD27. Using reverse genetics, we show that
      AtD27 is required for the inhibition of secondary bud outgrowth and that
      exogenous application of the synthetic SL GR24 can rescue the increased branching
      phenotype of an Atd27 mutant. Furthermore, we use grafting to demonstrate that
      AtD27 operates on a nonmobile precursor upstream of MAX1 in the SL biosynthesis
      pathway. Consistent with the plastid localization of OsD27, we also show that
      AtD27 possesses a functional plastid transit peptide. We demonstrate that AtD27
      transcripts are subject to both local feedback and auxin-dependent signals,
      albeit to a lesser extent than MAX3 and MAX4, suggesting that early steps in SL
      biosynthesis are coregulated at the transcriptional level. By identifying an
      additional component of the canonical SL biosynthesis pathway in Arabidopsis, we
      provide a new tool to investigate the regulation of shoot branching and other SL
      dependent developmental processes.

PMID- 22623517
TI  - Altered chloroplast development and delayed fruit ripening caused by mutations in
      a zinc metalloprotease at the lutescent2 locus of tomato.
AB  - The chloroplast is the site of photosynthesis in higher plants but also functions
      as the center of synthesis for primary and specialized metabolites including
      amino acids, fatty acids, starch, and diverse isoprenoids. Mutants that disrupt
      aspects of chloroplast function represent valuable tools for defining structural
      and biochemical regulation of the chloroplast and its interplay with whole-plant
      structure and function. The lutescent1 (l1) and l2 mutants of tomato (Solanum
      lycopersicum) possess a range of chlorophyll-deficient phenotypes including
      reduced rates of chlorophyll synthesis during deetiolation and enhanced rates of
      chlorophyll loss in leaves and fruits as they age, particularly in response to
      high-light stress and darkness. In addition, the onset of fruit ripening is
      delayed in lutescent mutants by approximately 1 week although once ripening is
      initiated they ripen at a normal rate and accumulation of carotenoids is not
      impaired. The l2 locus was mapped to the long arm of chromosome 10 and positional
      cloning revealed the existence of a premature stop codon in a chloroplast
      targeted zinc metalloprotease of the M50 family that is homologous to the
      Arabidopsis (Arabidopsis thaliana) gene ETHYLENE-DEPENDENT GRAVITROPISM DEFICIENT
      AND YELLOW-GREEN1. Screening of tomato germplasm identified two additional l2
      mutant alleles. This study suggests a role for the chloroplast in mediating the
      onset of fruit ripening in tomato and indicates that chromoplast development in
      fruit does not depend on functional chloroplasts.

PMID- 22623519
TI  - Endoscopic ultrasound-guided fine-needle aspiration diagnosis of large cell
      neuroendocrine carcinoma of the gallbladder and common bile duct: report of a
      case.
AB  - Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) allows a reliable
      and accurate diagnosis of neoplasms of the gallbladder and bile ducts. We report
      the cytopathologic findings of a case of large cell neuroendocrine carcinoma
      (LCNEC) of the gallbladder and extrahepatic bile ducts in a 67-year-old woman who
      presented with progressive abdominal pain and jaundice. EUS-FNA of the mass
      involving the common bile duct and of a porta hepatis lymph node showed abundant
      cellularity with tumor cells arranged singly and occasionally in tight and loose
      clusters and rosette-like structures in a background showing extensive necrotic
      debris. The tumor cells were predominantly plasmacytoid, showed a moderate amount
      of focally vacuolated cytoplasm and large round to oval hyperchromatic nuclei
      with prominent nucleoli, numerous mitoses, and apoptotic bodies. The differential
      diagnosis included poorly differentiated adenocarcinoma, lymphoma, melanoma, and
      poorly differentiated neuroendocrine carcinoma (NEC), large cell type. The tumor
      cells were strongly and diffusely positive for cytokeratin AE1/AE3, CD56,
      synaptophysin, and chromogranin and showed a very high proliferative fraction on
      Ki67 staining, supporting the diagnosis of a high-grade NEC. Due to the large
      size of the neoplastic cells, moderate amounts of cytoplasm and prominent
      nucleoli, a diagnosis of LCNEC was made on the EUS-FNA sample. Despite the prompt
      institution of chemotherapy, the patient died shortly thereafter and the
      diagnosis was confirmed at autopsy. This is to our knowledge the first case of
      LCNEC of the gallbladder and bile ducts diagnosed by EUS-FNA.

PMID- 22623520
TI  - Acute effects of methiocarb on oxidative damage and the protective effects of
      vitamin E and taurine in the liver and kidney of Wistar rats.
AB  - Methiocarb (MC) is a widely used carbamate pesticide in agriculture and health
      programs. Although the main molecular mechanism of carbamate toxicity involves
      acetylcholinesterase inhibition, studies have also implicated the induction of
      oxidative stress. Therefore, the present study was aimed to evaluate the effect
      of acute MC exposure on lipid peroxidation, antioxidant defense systems,
      histological changes in Wistar rats and the protective effect of pretreatment
      with vitamin E and taurine. A total of 48 rats were randomly divided into six
      groups. Rats in group I were given corn oil, while those in group III were dosed
      with vitamin E (100 mg/kg body weight (b.w.)) and in group V were dosed with
      taurine (50 mg/kg b.w.). Rats in group II were administered with MC only (25
      mg/kg b.w., 1/4 of median lethal dose (LD(50))), while those in groups IV and VI
      were pretreated with vitamin E (100 mg/kg b.w.) and taurine (50 mg/kg b.w.) for
      20 days, respectively, and then exposed to MC (25 mg/kg b.w.). The rats
      administered with MC showed significant increase in the levels of malondialdehyde
      in the liver and kidney as an index of lipid peroxidation. Levels of glutathione
      and activities of superoxide dismutase, catalase and glutathione peroxidase were
      significantly increased, while activity of glutathione reductase remained
      unchanged in both the tissues after MC treatment. Mild degenerative histological
      changes were observed in liver tissue, while the changes in kidney tissue were
      more severe then liver after MC treatment. Pretreatment with vitamin E and
      taurine resulted in a significant decrease in the lipid peroxidation and
      alleviating effects on antioxidant defense systems in both the tissues, while
      protective effects on the histological changes were shown only in kidney when
      compared with liver. In conclusion, the study has demonstrated that the acute MC
      exposure in Wistar rats caused oxidative damage on liver and kidney, which were
      partly ameliorated by the pretreatment of vitamin E and taurine.

PMID- 22623518
TI  - Pleiotropic phenotypes of the sticky peel mutant provide new insight into the
      role of CUTIN DEFICIENT2 in epidermal cell function in tomato.
AB  - Plant epidermal cells have evolved specialist functions associated with
      adaptation to stress. These include the synthesis and deposition of specialized
      metabolites such as waxes and cutin together with flavonoids and anthocyanins,
      which have important roles in providing a barrier to water loss and protection
      against UV radiation, respectively. Characterization of the sticky peel (pe)
      mutant of tomato (Solanum lycopersicum) revealed several phenotypes indicative of
      a defect in epidermal cell function, including reduced anthocyanin accumulation,
      a lower density of glandular trichomes, and an associated reduction in trichome
      derived terpenes. In addition, pe mutant fruit are glossy and peels have
      increased elasticity due to a severe reduction in cutin biosynthesis and altered
      wax deposition. Leaves of the pe mutant are also cutin deficient and the
      epicuticular waxes contain a lower proportion of long-chain alkanes. Direct
      measurements of transpiration, together with chlorophyll-leaching assays,
      indicate increased cuticular permeability of pe leaves. Genetic mapping revealed
      that the pe locus represents a new allele of CUTIN DEFICIENT2 (CD2), a member of
      the class IV homeodomain-leucine zipper gene family, previously only associated
      with cutin deficiency in tomato fruit. CD2 is preferentially expressed in
      epidermal cells of tomato stems and is a homolog of Arabidopsis (Arabidopsis
      thaliana) ANTHOCYANINLESS2 (ANL2). Analysis of cuticle composition in leaves of
      anl2 revealed that cutin accumulates to approximately 60% of the levels observed
      in wild-type Arabidopsis. Together, these data provide new insight into the role
      of CD2 and ANL2 in regulating diverse metabolic pathways and in particular, those
      associated with epidermal cells.

PMID- 22623521
TI  - Lipoic acid mitigates bisphenol A-induced testicular mitochondrial toxicity in
      rats.
AB  - Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. BPA
      is used in the production of polycarbonate plastics and epoxy resins used in
      manufacturing plastic baby bottles and lining of food cans. In this study, we
      investigated the BPA-induced testicular oxidative stress and perturbation of
      mitochondrial marker enzymes in male albino rats and its amelioration by alpha
      lipoic acid (LA). Rats were administered a dose of BPA (10 mg/kg body weight)
      orally for 14 days. This resulted in decreased testes weight, total testicular
      protein content, testicular enzymes such as acid phosphatase, alkaline
      phosphatase and lactate dehydrogenase and decline in activities of marker
      mitochondrial enzymes such as succinate dehydrogenase, malate dehydrogenase,
      isocitrate dehydrogenase, monoamine oxidase and NADH dehydrogenase. The serum
      testosterone and total antioxidant status were reduced. Besides, it also affected
      the activities of testicular antioxidant enzymes such as glutathione reductase,
      glutathione peroxidase, superoxide dismutase and catalase. BPA also caused lipid
      peroxidation and decrease in reduced glutathione content of mitochondria. The co
      administration of LA (20 mg/kg body weight; orally for 14 days) together with BPA
      resulted in restoration of the mitochondrial marker enzyme activities and
      increasing enzymatic and non-enzymatic antioxidants of mitochondria. The obtained
      results demonstrated that LA has a potential role in mitigating BPA-induced
      mitochondrial toxicity through antioxidant mechanism or by direct free radical
      scavenging activity.

PMID- 22623524
TI  - Ideal glass transitions by random pinning.
AB  - We study the effect of freezing the positions of a fraction c of particles from
      an equilibrium configuration of a supercooled liquid at a temperature T. We show
      that within the random first-order transition theory pinning particles leads to
      an ideal glass transition for a critical fraction c = c(K)(T) even for moderate
      supercooling; e.g., close to the Mode-Coupling transition temperature. First we
      derive the phase diagram in the T - c plane by mean field approximations. Then,
      by applying a real-space renormalization group method, we obtain the critical
      properties for |c - c(K)(T)| -> 0, in particular the divergence of length and
      time scales, which are dominated by two zero-temperature fixed points. We also
      show that for c = c(K)(T) the typical distance between frozen particles is
      related to the static point-to-set length scale of the unconstrained liquid. We
      discuss what are the main differences when particles are frozen in other
      geometries and not from an equilibrium configuration. Finally, we explain why the
      glass transition induced by freezing particles provides a new and very promising
      avenue of research to probe the glassy state and ascertain, or disprove, the
      validity of the theories of the glass transition.

PMID- 22623522
TI  - Mitogen-activated protein kinase phosphatase (Mkp)-1 protects mice against
      acetaminophen-induced hepatic injury.
AB  - c-Jun N-terminal kinase (JNK) activation promotes hepatocyte death during
      acetaminophen overdose, a common cause of drug-induced liver failure. While
      mitogen-activated protein kinase (MAPK) phosphatase (Mkp)-1 is a critical
      negative regulator of JNK MAPK, little is known about the role of Mkp-1 during
      hepatotoxicity. In this study, we evaluated the role of Mkp-1 during acute
      acetaminophen toxicity. Mkp-1+/+ and Mkp-1-/- mice were dosed ip with vehicle or
      acetaminophen at 300 mg/kg (for mechanistic studies) or 400 mg/kg (for survival
      studies). Tissues were collected 1-6 hr post 300 mg/kg dosing to assess
      glutathione levels, organ damage, and MAPK activation. Mkp-1-/- mice exhibited
      more rapid plasma clearance of acetaminophen than did Mkp-1+/+ mice, indicated by
      a quicker decline of plasma acetaminophen level. Moreover, Mkp-1-/- mice suffered
      more severe liver injury, indicated by higher plasma alanine transaminase
      activity and more extensive centrilobular apoptosis and necrosis. Hepatic JNK
      activity in Mkp-1-/- mice was higher than in Mkp-1+/+ mice. Finally, Mkp-1-/-
      mice displayed a lower overall survival rate and shorter median survival time
      after dosing with 400 mg/kg acetaminophen. The more severe phenotype exhibited by
      Mkp-1-/- mice indicates that Mkp-1 plays a protective role during acute
      acetaminophen overdose, potentially through regulation of JNK.

PMID- 22623525
TI  - Surface enhanced Raman spectroscopy on a flat graphene surface.
AB  - Surface enhanced Raman spectroscopy (SERS) is an attractive analytical technique,
      which enables single-molecule sensitive detection and provides its special
      chemical fingerprints. During the past decades, researchers have made great
      efforts towards an ideal SERS substrate, mainly including pioneering works on the
      preparation of uniform metal nanostructure arrays by various nanoassembly and
      nanotailoring methods, which give better uniformity and reproducibility.
      Recently, nanoparticles coated with an inert shell were used to make the enhanced
      Raman signals cleaner. By depositing SERS-active metal nanoislands on an
      atomically flat graphene layer, here we designed a new kind of SERS substrate
      referred to as a graphene-mediated SERS (G-SERS) substrate. In the graphene/metal
      combined structure, the electromagnetic "hot" spots (which is the origin of a
      huge SERS enhancement) created by the gapped metal nanoislands through the
      localized surface plasmon resonance effect are supposed to pass through the
      monolayer graphene, resulting in an atomically flat hot surface for Raman
      enhancement. Signals from a G-SERS substrate were also demonstrated to have
      interesting advantages over normal SERS, in terms of cleaner vibrational
      information free from various metal-molecule interactions and being more stable
      against photo-induced damage, but with a comparable enhancement factor.
      Furthermore, we demonstrate the use of a freestanding, transparent and flexible
      "G-SERS tape" (consisting of a polymer-layer-supported monolayer graphene with
      sandwiched metal nanoislands) to enable direct, real time and reliable detection
      of trace amounts of analytes in various systems, which imparts high efficiency
      and universality of analyses with G-SERS substrates.

PMID- 22623526
TI  - Mechanism of enhanced mechanical stability of a minimal RNA kissing complex
      elucidated by nonequilibrium molecular dynamics simulations.
AB  - An RNA kissing loop from the Moloney murine leukemia virus (MMLV) exhibits
      unusual mechanical stability despite having only two intermolecular base pairs.
      Mutations at this junction have been shown to destabilize genome dimerization,
      with concomitant reductions in viral packaging efficiency and infectivity.
      Optical tweezers experiments have shown that it requires as much force to break
      the MMLV kissing-loop complex as is required to unfold an 11-bp RNA hairpin [Li
      PTX, Bustamante C, Tinoco I (2006) Proc Natl Acad Sci USA 103:15847-15852]. Using
      nonequilibrium all-atom molecular dynamics simulations, we have developed a
      detailed model for the kinetic intermediates of the force-induced dissociation of
      the MMLV dimerization initiation site kissing loop. Two hundred and eight
      dissociation events were simulated (approximately 16 MUs total simulation time)
      under conditions of constant applied external force, which we use to construct a
      Markov state model for kissing-loop dissociation. We find that the complex
      undergoes a conformational rearrangement, which allows for equal distribution of
      the applied force among all of the intermolecular hydrogen bonds, which is
      intrinsically more stable than the sequential unzipping of an ordinary hairpin.
      Stacking interactions with adjacent, unpaired loop adenines further stabilize the
      complex by increasing the repair rate of partially broken H-bonds. These stacking
      interactions are prominently featured in the transition state, which requires
      additional coordinates orthogonal to the end-to-end extension to be uniquely
      identified. We propose that these stabilizing features explain the unusual
      stability of other retroviral kissing-loop complexes such as the HIV dimerization
      site.

PMID- 22623527
TI  - Flexure-FET biosensor to break the fundamental sensitivity limits of
      nanobiosensors using nonlinear electromechanical coupling.
AB  - In this article, we propose a Flexure-FET (flexure sensitive field effect
      transistor) ultrasensitive biosensor that utilizes the nonlinear
      electromechanical coupling to overcome the fundamental sensitivity limits of
      classical electrical or mechanical nanoscale biosensors. The stiffness of the
      suspended gate of Flexure-FET changes with the capture of the target
      biomolecules, and the corresponding change in the gate shape or deflection is
      reflected in the drain current of FET. The Flexure-FET is configured to operate
      such that the gate is biased near pull-in instability, and the FET-channel is
      biased in the subthreshold regime. In this coupled nonlinear operating mode, the
      sensitivity (S) of Flexure-FET with respect to the captured molecule density
      (N(s)) is shown to be exponentially higher than that of any other electrical or
      mechanical biosensor. In other words, while S(Flexure) ~ e(gamma1 [square root]Ns
      gamma2Ns), classical electrical or mechanical biosensors are limited to
      S(classical) ~ gamma(3)N(S) or gamma(4) ln(N(S)), where gamma(i) are sensor
      specific constants. In addition, the proposed sensor can detect both charged and
      charge-neutral biomolecules, without requiring a reference electrode or any
      sophisticated instrumentation, making it a potential candidate for various low
      cost, point-of-care applications.

PMID- 22623528
TI  - Structural basis of hepatitis C virus neutralization by broadly neutralizing
      antibody HCV1.
AB  - Hepatitis C virus (HCV) infects more than 2% of the global population and is a
      leading cause of liver cirrhosis, hepatocellular carcinoma, and end-stage liver
      diseases. Circulating HCV is genetically diverse, and therefore a broadly
      effective vaccine must target conserved T- and B-cell epitopes of the virus.
      Human mAb HCV1 has broad neutralizing activity against HCV isolates from at least
      four major genotypes and protects in the chimpanzee model from primary HCV
      challenge. The antibody targets a conserved antigenic site (residues 412-423) on
      the virus E2 envelope glycoprotein. Two crystal structures of HCV1 Fab in complex
      with an epitope peptide at 1.8-A resolution reveal that the epitope is a beta
      hairpin displaying a hydrophilic face and a hydrophobic face on opposing sides of
      the hairpin. The antibody predominantly interacts with E2 residues Leu(413) and
      Trp(420) on the hydrophobic face of the epitope, thus providing an explanation
      for how HCV isolates bearing mutations at Asn(415) on the same binding face
      escape neutralization by this antibody. The results provide structural
      information for a neutralizing epitope on the HCV E2 glycoprotein and should help
      guide rational design of HCV immunogens to elicit similar broadly neutralizing
      antibodies through vaccination.

PMID- 22623529
TI  - Some strains of Plasmodium falciparum, a human malaria parasite, evade the
      complement-like system of Anopheles gambiae mosquitoes.
AB  - Plasmodium falciparum lines differ in their ability to infect mosquitoes. The
      Anopheles gambiae L3-5 refractory (R) line melanizes most Plasmodium species,
      including the Brazilian P. falciparum 7G8 line, but it is highly susceptible to
      some African P. falciparum strains such as 3D7, NF54, and GB4. We investigated
      whether these lines differ in their ability to evade the mosquito immune system.
      Silencing key components of the mosquito complement-like system [thioester
      containing protein 1 (TEP1), leucine-rich repeat protein 1, and Anopheles
      Plasmodium-responsive leucine-rich repeat protein 1] prevented melanization of
      7G8 parasites, reverting the refractory phenotype. In contrast, it had no effect
      on the intensity of infection with NF54, suggesting that this line is able to
      evade TEP1-mediated lysis. When R females were coinfected with a line that is
      melanized (7G8) and a line that survives (3D7), the coinfection resulted in mixed
      infections with both live and encapsulated parasites on individual midguts. This
      finding shows that survival of individual parasites is parasite-specific and not
      systemic in nature, because parasites can evade TEP1-mediated lysis even when
      other parasites are melanized in the same midgut. When females from an extensive
      genetic cross between R and susceptible A. gambiae (G3) mosquitoes were infected
      with P. berghei, encapsulation was strongly correlated with the TEP1-R1 allele.
      However, P. falciparum 7G8 parasites were no longer encapsulated by females from
      this cross, indicating that the TEP1-R1 allele is not sufficient to melanize this
      line. Evasion of the A. gambiae immune system by P. falciparum may be the result
      of parasite adaptation to sympatric mosquito vectors and may be an important
      factor driving malaria transmission.

PMID- 22623530
TI  - Functional roles of fructose.
AB  - During the periimplantation period of pregnancy, pig blastocysts undergo
      morphological changes and differentiation requiring secretion and transport of
      nutrients (histotroph) into the uterine lumen. Of these nutrients, glucose is
      converted to fructose, an isomer of glucose, by conceptus trophectoderm. Although
      glucose is an energy source for proliferation and growth of mammalian cells, the
      role of fructose in uterine histotroph is unclear although it is the most
      abundant hexose sugar in fetal blood and fluids of ungulate mammals (e.g., cows,
      sheep, and pigs). In this study, we used porcine trophectoderm cells to determine
      that fructose increased cell proliferation, as did glucose. Western blot analyses
      of porcine trophectoderm cell extracts revealed that fructose increased the
      abundance of phosphorylated-RPS6K, -EIF4EBP1, and -RPS6 over basal levels within
      30 min, and those levels remained elevated to 120 min. Phosphorylation of both
      RPS6K and EIF4EBP1 proteins in response to fructose was inhibited by inhibitors
      of both PI3K and MTOR. Further, when we investigated the inhibition of glutamine
      fructose-6-phosphate transaminase 1 (GFPT1) by azaserine (an inhibitor of GFPT1)
      and GFPT1 siRNA, we found that MTOR-RPS6K and MTOR-EIF4EBP1 signaling in response
      to fructose is mediated via GFPT1 activation and the hexosamine pathway. We
      further demonstrated that fructose stimulates the production of hyaluronic acid
      via GFPT1 and the hexosamine biosynthesis pathway. Collectively, these results
      demonstrate critical roles for fructose that are mediated via the hexosamine
      biosynthesis pathway to stimulate MTOR cell signaling, proliferation of porcine
      trophectoderm cells, and synthesis of hyaluronic acid, a significant
      glycosaminoglycan in the pregnant uterus.

PMID- 22623531
TI  - Functional genomics identifies therapeutic targets for MYC-driven cancer.
AB  - MYC oncogene family members are broadly implicated in human cancers, yet are
      considered "undruggable" as they encode transcription factors. MYC also carries
      out essential functions in proliferative tissues, suggesting that its inhibition
      could cause severe side effects. We elected to identify synthetic lethal
      interactions with c-MYC overexpression (MYC-SL) in a collection of ~3,300
      druggable genes, using high-throughput siRNA screening. Of 49 genes selected for
      follow-up, 48 were confirmed by independent retesting and approximately one-third
      selectively induced accumulation of DNA damage, consistent with enrichment in DNA
      repair genes by functional annotation. In addition, genes involved in histone
      acetylation and transcriptional elongation, such as TRRAP and BRD4, were
      identified, indicating that the screen revealed known MYC-associated pathways.
      For in vivo validation we selected CSNK1e, a kinase whose expression correlated
      with MYCN amplification in neuroblastoma (an established MYC-driven cancer).
      Using RNAi and available small-molecule inhibitors, we confirmed that inhibition
      of CSNK1e halted growth of MYCN-amplified neuroblastoma xenografts. CSNK1e had
      previously been implicated in the regulation of developmental pathways and
      circadian rhythms, whereas our data provide a previously unknown link with
      oncogenic MYC. Furthermore, expression of CSNK1e correlated with c-MYC and its
      transcriptional signature in other human cancers, indicating potential broad
      therapeutic implications of targeting CSNK1e function. In summary, through a
      functional genomics approach, pathways essential in the context of oncogenic MYC
      but not to normal cells were identified, thus revealing a rich therapeutic space
      linked to a previously "undruggable" oncogene.

PMID- 22623532
TI  - Exposure therapy triggers lasting reorganization of neural fear processing.
AB  - A single session of exposure therapy can eliminate recalcitrant and disabling
      fear of phobogenic objects or situations. We studied neural mechanisms of this
      remarkable outcome by monitoring changes in brain activity as a result of
      successful 2-h treatment. Before treatment, phobogenic images excited activity in
      a network of regions, including amygdala, insula, and cingulate cortex, relative
      to neutral images. Successful therapy dampened responsiveness in this fear
      sensitive network while concomitantly heightening prefrontal involvement. Six
      months later, dampened fear-network activity persisted but without prefrontal
      engagement. Additionally, individual differences in the magnitude of visual
      cortex activations recorded shortly after therapy predicted therapeutic outcomes
      6 mo later, which involved persistently diminished visual responsiveness to
      phobogenic images. Successful therapy thus entailed stable reorganization of
      neural responses to initially feared stimuli. These effects were linked to fear
      extinction mechanisms identified in animal models, thus opening new opportunities
      for the treatment and prevention of debilitating anxiety disorders.

PMID- 22623533
TI  - Orally bioavailable small-molecule inhibitor of transcription factor Stat3
      regresses human breast and lung cancer xenografts.
AB  - Computer-aided lead optimization derives a unique, orally bioavailable inhibitor
      of the signal transducer and activator of transcription (Stat)3 Src homology 2
      domain. BP-1-102 binds Stat3 with an affinity (K(D)) of 504 nM, blocks Stat3
      phospho-tyrosine (pTyr) peptide interactions and Stat3 activation at 4-6.8 MUM,
      and selectively inhibits growth, survival, migration, and invasion of Stat3
      dependent tumor cells. BP-1-102-mediated inhibition of aberrantly active Stat3 in
      tumor cells suppresses the expression of c-Myc, Cyclin D1, Bcl-xL, Survivin,
      VEGF, and Kruppel-like factor 8, which is identified as a Stat3 target gene that
      promotes Stat3-mediated breast tumor cell migration and invasion. Treatment of
      breast cancer cells with BP-1-102 further blocks Stat3-NF-kappaB cross-talk, the
      release of granulocyte colony-stimulating factor, soluble intercellular adhesion
      molecule 1, macrophage migration-inhibitory factor/glycosylation-inhibiting
      factor, interleukin 1 receptor antagonist, and serine protease inhibitor protein
      1, and the phosphorylation of focal adhesion kinase and paxillin, while enhancing
      E-cadherin expression. Intravenous or oral gavage delivery of BP-1-102 furnishes
      micromolar or microgram levels in tumor tissues and inhibits growth of human
      breast and lung tumor xenografts.

PMID- 22623534
TI  - Emotions promote social interaction by synchronizing brain activity across
      individuals.
AB  - Sharing others' emotional states may facilitate understanding their intentions
      and actions. Here we show that networks of brain areas "tick together" in
      participants who are viewing similar emotional events in a movie. Participants'
      brain activity was measured with functional MRI while they watched movies
      depicting unpleasant, neutral, and pleasant emotions. After scanning,
      participants watched the movies again and continuously rated their experience of
      pleasantness-unpleasantness (i.e., valence) and of arousal-calmness. Pearson's
      correlation coefficient was used to derive multisubject voxelwise similarity
      measures [intersubject correlations (ISCs)] of functional MRI data. Valence and
      arousal time series were used to predict the moment-to-moment ISCs computed using
      a 17-s moving average. During movie viewing, participants' brain activity was
      synchronized in lower- and higher-order sensory areas and in corticolimbic
      emotion circuits. Negative valence was associated with increased ISC in the
      emotion-processing network (thalamus, ventral striatum, insula) and in the
      default-mode network (precuneus, temporoparietal junction, medial prefrontal
      cortex, posterior superior temporal sulcus). High arousal was associated with
      increased ISC in the somatosensory cortices and visual and dorsal attention
      networks comprising the visual cortex, bilateral intraparietal sulci, and frontal
      eye fields. Seed-voxel-based correlation analysis confirmed that these sets of
      regions constitute dissociable, functional networks. We propose that negative
      valence synchronizes individuals' brain areas supporting emotional sensations and
      understanding of another's actions, whereas high arousal directs individuals'
      attention to similar features of the environment. By enhancing the synchrony of
      brain activity across individuals, emotions may promote social interaction and
      facilitate interpersonal understanding.

PMID- 22623535
TI  - Perfusion and flow extraction product as potential discriminators in untreated
      follicular and diffuse large B cell lymphomas using volume perfusion CT with
      attempt at histopathologic explanation.
AB  - OBJECTIVE: The purpose of this article is to measure perfusion parameters,
      including transit constant (K(trans)), in untreated follicular and diffuse large
      B cell lymphoma using volume perfusion CT, to establish their discriminating role
      and to search for a possible histopathologic background. SUBJECTS AND METHODS:
      Between January 2010 and June 2011, 46 consecutive patients with untreated
      histologically confirmed follicular lymphoma (n = 16) or diffuse large B cell
      lymphoma (n = 30) were enrolled. A 40-second volume perfusion CT of the tumor
      bulk using 6.9-cm z-axis coverage and a total of 26 volume measurements was
      performed. Blood flow (BF), blood volume (BV), and K(trans) were determined.
      Tumor size was recorded as the product of long- and short-axis diameters. In 13
      of 46 patients, pathologic specimens of an appropriate size were available for
      assessment of microvessel density (MVD) and microvascular luminal diameter for
      comparison with volume perfusion CT measurements. RESULTS: Mean BF, BV, and
      K(trans) values were significantly higher in follicular lymphoma than in diffuse
      large B cell lymphoma, even after controlling for patient age and tumor size (p <
      0.05, respectively). Although MVD was slightly, but not significantly, higher in
      follicular lymphoma versus diffuse large B cell lymphoma (p > 0.05),
      microvascular luminal diameter was significantly larger in follicular lymphoma
      than in diffuse large B cell lymphoma (p < 0.05). We defined cutoff values for
      BF, BV, and K(trans). If the cutoff points are met for all three parameters, the
      overall accuracy for correctly identifying diffuse large B cell lymphoma and
      follicular lymphoma was 90.5% and 87.5%, respectively. CONCLUSION: Volume
      perfusion CT allows assessment of differences in vascularity of follicular and
      diffuse large B cell lymphomas, reflecting vascular luminal variability and
      histopathologic anatomy.

PMID- 22623536
TI  - Prevalence of honorary coauthorship in the American Journal of Roentgenology.
AB  - OBJECTIVE: The objective of our study was to determine the prevalence of honorary
      authorship in articles published in the American Journal of Roentgenology (AJR)
      and to evaluate the factors that might influence the perception of honorary
      authorship. MATERIALS AND METHODS: Corresponding authors of 1333 Original
      Research articles published in AJR between 2003 and 2010 were invited by e-mail
      to complete a Web-based, self-administered survey. Univariable analysis of sample
      proportions was performed using the chi-square test. Multivariable logistic
      regression models were used to assess the independent factors that were
      associated with the probability of honorary authorship. RESULTS: Responses were
      received from authors of 490 articles (36.8% response rate). Most respondents
      were aware of the authorship guidelines proposed by the International Committee
      of Medical Journal Editors (n = 399, 81.4%) and the issue of honorary authorship
      (n = 353, 72.0%). Authorship was most commonly decided by the first author (n =
      256, 52.2%). One hundred twenty-one authors (24.7%) perceived that one or more
      coauthors listed for the respective article did not make sufficient
      contributions. Factors most strongly associated with honorary authorship included
      a work environment where a senior department member was automatically listed
      (odds ratio [OR], 1.33), the suggestion that an honorary author should be
      included (OR, 5.96), and the perception that a coauthor performed only a single
      nonauthor task (i.e., reviewing the manuscript: OR, 1.54). CONCLUSION: A
      substantial proportion of articles had evidence of honorary authorship. The rate
      of honorary authors was higher among authors who worked in an environment where
      senior members were routinely added to all manuscripts submitted for publication,
      authors who perceived that a coauthor listed had only reviewed the manuscript,
      and authors who reported that someone suggested they should include an honorary
      author.

PMID- 22623537
TI  - Hematuria: a problem-based imaging algorithm illustrating the recent Dutch
      guidelines on hematuria.
AB  - OBJECTIVE: To present a problem-based algorithm in the work-up of patients with
      Hematuria. Since the 2010 Dutch Guideline on Hematuria was problem-based, this
      served as an illustration for such an approach.. CONCLUSION: The work-up of
      hematuria should be individualized and risk-based. Given the a priori low
      likelihood of cancer in hematuria, risk categories should be established and
      imaging algorithms should be tailored to populations at low-risk, medium-risk and
      high-risk for developing urothelial cancer.

PMID- 22623538
TI  - Imaging in the follow-up of renal cell carcinoma.
AB  - OBJECTIVE: The purpose of this article is to review the follow-up strategies used
      after treatment or for active surveillance of renal cell cancer and to describe
      the normal posttreatment findings and the distribution and the signs of relapsed
      disease. CONCLUSION: Imaging follow-up protocols should be tailored according to
      the clinical scenario. Further experience is necessary to better refine imaging
      strategies, especially regarding follow-up of patients after thermal ablation or
      antiangiogenic therapy and those being maintained on active surveillance.

PMID- 22623539
TI  - Overview of dynamic contrast-enhanced MRI in prostate cancer diagnosis and
      management.
AB  - OBJECTIVE: This article is a primer on the technical aspects of performing a high
      quality dynamic contrast-enhanced MRI (DCE-MRI) examination of the prostate
      gland. CONCLUSION: DCE-MRI is emerging as a useful clinical technique as part of
      a multi-parametric approach for evaluating the extent of primary and recurrent
      prostate cancer. Performing a high-quality DCE-MRI examination requires a good
      understanding of the technical aspects and limitations of image acquisition and
      postprocessing techniques.

PMID- 22623540
TI  - Renal cell carcinoma and mimics: pathologic primer for radiologists.
AB  - OBJECTIVE: The purpose of this article is to present a primer to review the gross
      and microscopic characteristics of the common types of renal cell carcinoma
      (RCC), such as clear cell RCC, papillary RCC, and chromophobe RCC. Renal
      oncocytoma and several new and emerging types of RCC are also described, such as
      tubulocystic carcinoma, acquired cystic kidney disease-associated RCC, clear cell
      papillary RCC, and oncocytic papillary RCC. CONCLUSION: This primer provides a
      concise description of the pathologic characteristics fo RCC for radiologists.

PMID- 22623541
TI  - What a differential a virus makes: a practical approach to thoracic imaging
      findings in the context of HIV infection--part 1, pulmonary findings.
AB  - OBJECTIVE: The Centers for Disease Control and Prevention reported more than one
      million people with HIV infection in the United States in 2006, an increase of
      11% over 3 years. Worldwide, nearly 34 million people are infected with HIV.
      Pulmonary disease accounts for 30-40% of acute hospitalizations of HIV-infected
      patients, underscoring the importance of understanding the pulmonary
      manifestations in this population. When presented with a chest radiograph or CT
      image of a patient with the clinical history of HIV infection, one approach is to
      start by identifying and categorizing key imaging findings. In some instances,
      the key findings may be further subcategorized to narrow the differential
      diagnosis, such as distinguishing between perilymphatic distribution and the
      random distribution of micronodules. The differential diagnosis of these key
      imaging findings can also be further refined by incorporating clinical data, such
      as patient demographics, CD4 count, and presenting symptoms. Finally, the change
      of thoracic disease and clinical status in response to treatment provides
      important diagnostic information. The purpose of this article is to discuss
      pulmonary findings in patients with HIV. CONCLUSION: By developing a systematic
      and practical approach to key pulmonary imaging findings in HIV-infected
      patients, radiologists can generate clinically relevant and succinct differential
      diagnoses and thereby improve patient care.

PMID- 22623542
TI  - What a differential a virus makes: a practical approach to thoracic imaging
      findings in the context of HIV infection--part 2, extrapulmonary findings,
      chronic lung disease, and immune reconstitution syndrome.
AB  - OBJECTIVE: The Centers for Disease Control and Prevention reported more than one
      million people with HIV infection in the United States in 2006, an increase of
      11% over 3 years. Worldwide, nearly 34 million people are infected with HIV.
      Pulmonary disease accounts for 30-40% of acute hospitalizations of HIV
      seropositive patients, underscoring the importance of understanding the range of
      cardiothoracic imaging findings associated with HIV infection. This article will
      cover extrapulmonary thoracic diseases, chronic lung diseases, and immune
      reconstitution inflammatory syndrome in HIV-infected patients. Our approach is
      focused on the radiologist's perspective by recognizing and categorizing key
      imaging findings to generate a differential diagnosis. The differential diagnosis
      can be further refined by incorporating clinical data, such as patient
      demographics, CD4 count, and presenting symptoms. In addition, with prolonged
      survival of HIV-infected patients in the era of highly active antiretroviral
      therapy, radiologists can also benefit from awareness of imaging features of a
      myriad of chronic cardiopulmonary diseases in this patient population. Finally,
      the change of imaging findings and clinical status in response to treatment
      provides important diagnostic information, such as in immune reconstitution
      syndrome. CONCLUSION: Developing a practical approach to key cardiothoracic
      imaging findings in HIV-infected patients will aid the radiologist in generating
      a clinically relevant differential diagnosis and interpretation, thereby
      improving patient care.

PMID- 22623543
TI  - Panel discussion: pulmonary embolism imaging and outcomes.

PMID- 22623544
TI  - Current role of imaging in the diagnosis and management of pulmonary
      hypertension.
AB  - OBJECTIVE: The purpose of this review is to describe classification schemes and
      imaging findings in the diagnosis and management of pulmonary hypertension.
      CONCLUSION: Pulmonary hypertension is a complex pathophysiologic condition in
      which several clinical entities increase pressure in the pulmonary circulation,
      progressively impairing cardiopulmonary function and, if untreated, causing right
      ventricular failure. Current classification schemes emphasize the necessity of an
      early, accurate etiologic diagnosis for a tailored therapeutic approach. Imaging
      plays an increasingly important role in the diagnosis and management of suspected
      pulmonary hypertension.

PMID- 22623545
TI  - Risk-benefit analysis of pulmonary CT angiography in patients with suspected
      pulmonary embolus.
AB  - OBJECTIVE: The objective of our study was to estimate the mortality benefit-to
      risk ratio of pulmonary CT angiography (CTA) by setting (ambulatory [emergency
      department or outpatient] or inpatient), age, and sex. MATERIALS AND METHODS: A
      retrospective evaluation of 1424 consecutive pulmonary CTA examinations was
      performed and the following information was recorded: examination setting,
      patient age, patient sex, pulmonary CTA interpretation for pulmonary embolus
      (PE), and CT radiation exposure (dose-length product). We estimated mortality
      benefit of pulmonary CTA by multiplying the rate of positive pulmonary CTA
      examinations by published estimates of mortality of untreated PE in ambulatory
      and inpatient settings. We estimated the lifetime attributable risk of cancer
      mortality due to radiation from pulmonary CTA by calculating the estimated
      effective dose and using sex-specific polynomial equations derived from the
      Biological Effects of Ionizing Radiation VII report. We calculated benefit-to
      risk ratios by dividing the mortality benefit of preventing a fatal PE by the
      mortality risk of a radiation-induced cancer. RESULTS: Pulmonary CTA diagnosed PE
      in 188 of 1424 patients (13.2%). Both inpatients (101/723, 14.0%) and emergency
      department patients (74/509, 14.5%) had significantly higher rates of PE than
      outpatients (13/192 [6.8%]). Males received significantly (p = 0.02451) higher
      radiation dose (9.7 mSv) than females (8.4 mSv), but males had a significantly (p
      < 0.0001) lower lifetime attributable risk of cancer mortality than females.
      Assuming an untreated PE mortality rate of 5% for ambulatory patients and 30% for
      inpatients, the benefit-to-risk ratio ranged from 25 for ambulatory patients to
      187 for inpatients. Ambulatory women had the lowest benefit-to-risk ratio.
      CONCLUSION: The benefit-to-risk ratio of pulmonary CTA in patients with suspected
      PE ranges from 25 to 187 and can be increased by optimizing the radiation dose.

PMID- 22623546
TI  - Pulmonary embolism diagnosis and mortality with pulmonary CT angiography versus
      ventilation-perfusion scintigraphy: evidence of overdiagnosis with CT?
AB  - OBJECTIVE: The purposes of this study were to determine whether pulmonary emboli
      diagnosed with pulmonary CT angiography (CTA) represent a milder disease spectrum
      than those diagnosed with ventilation-perfusion (V/Q) scintigraphy, to determine
      the trends in incidence and mortality among patients with the diagnosis of
      pulmonary embolism from 2000 to 2007, and to correlate incidence and mortality
      trends with imaging modality trends. MATERIALS AND METHODS: Diagnoses of
      pulmonary embolism from 2000 to 2007 at an urban academic medical center were
      retrospectively identified. Patient data were collected from the hospital
      database and the Social Security Death Index. Incident diagnoses, type of imaging
      used, and date of death were documented. Bivariate and multivariate analyses were
      used to explore the relations between imaging use and the incidence and mortality
      of pulmonary embolism. Logistic regression analysis was used to estimate the odds
      of death of pulmonary embolism diagnosed with pulmonary CTA versus V/Q
      scintigraphy. RESULTS: The cases of 2087 patients (1361 women, 726 men; mean age,
      61.8 years) with pulmonary embolism were identified. From 2000 to 2007 the
      incidence of pulmonary embolism increased from 0.69 to 0.91 per 100 admissions in
      strong correlation with increased use of pulmonary CTA. There was no change in
      mortality, but the case-fatality rate decreased from 5.7% to 3.3%. On average,
      pulmonary emboli diagnosed with pulmonary CTA were one half as lethal as those
      diagnosed with V/Q scintigraphy (odds ratio, 0.538; 95% CI, 0.314-0.921).
      CONCLUSION: The results of this study are evidence that the shift in imaging from
      V/Q scintigraphy to pulmonary CTA resulted in increased diagnosis of a less fatal
      spectrum of pulmonary embolic disease, raising the possibility of overdiagnosis.
      Outcome-based clinical trials with long-term follow-up would be helpful to
      further guide management.

PMID- 22623547
TI  - CT findings and long-term mortality after pulmonary embolism.
AB  - OBJECTIVE: The utility of CT findings in predicting long-term mortality in
      patients with acute pulmonary embolism (PE) is unknown. The purpose of this study
      is to retrospectively determine whether three CT findings--increased embolic
      burden, interventricular septal bowing toward the left ventricle, and right
      ventricle-to-left ventricle (RV/LV) diameter ratio greater than 1--are
      independent predictors of long-term all-cause mortality after acute PE. MATERIALS
      AND METHODS: A total of 1105 patients (47% female; mean age, 63 +/- 16 years)
      with CT scans positive for PE from January 1, 1997, to December 31, 2002, were
      included. Scans were independently interpreted by two observers, with a third
      independent observer reviewing discrepant cases. CT findings and clinical
      information were compared with all-cause mortality using univariate and
      multivariate logistic regression analyses. RESULTS: The median duration of
      survival was 6.2 years following acute PE, with estimated 10-year survival of
      37.4%. CT-derived embolic burden was associated with a very small decrease in
      long-term all-cause mortality in both univariate (hazard ratio [HR], 0.97; p <
      0.001) and multivariate (HR, 0.97; p < 0.001) analyses. Interventricular septal
      bowing and RV/LV diameter ratio were not significantly associated with long-term
      all-cause mortality. CONCLUSION: CT findings are not predictive of decreased long
      term survival after acute PE.

PMID- 22623548
TI  - Axial and reformatted four-chamber right ventricle-to-left ventricle diameter
      ratios on pulmonary CT angiography as predictors of death after acute pulmonary
      embolism.
AB  - OBJECTIVE: The purpose of this article is to retrospectively compare right
      ventricular-to-left ventricular (RV/LV) diameter ratios measured on the standard
      axial view versus the reformatted four-chamber view as predictors of mortality
      after acute pulmonary embolism (PE). MATERIALS AND METHODS: Six hundred seventy
      four consecutive patients (mean age, 58 years; 372 women) with a diagnosis of
      acute PE on pulmonary CT angiography were considered. The axial and reformatted
      four-chamber RV/LV diameter ratios were compared as predictors of 30-day all
      cause and PE-related mortality. RESULTS: Ninety-seven patients (14%) died within
      30 days; 39 deaths were PE related. There was no significant difference in the
      univariate hazard ratios (HRs) of axial and four-chamber RV/LV diameter ratios
      greater than 0.9 for both all-cause (HR, 2.13 [95% CI, 1.29-3.51] vs HR, 1.95
      [95% CI, 1.22-3.14]; p = 0.74) and PE-related (HR, 19.6 [95% CI, 2.70-143] vs HR,
      21.8 [95% CI, 2.99-158]; p = 1.0) mortality. Axial and four-chamber multivariate
      HRs accounting for potential confounders such as age and cancer were also similar
      for all-cause (HR, 1.79 [95% CI, 1.07-2.99] vs HR, 1.54 [95% CI, 0.95-2.49]; p =
      0.62) and PE-related (HR, 16.3 [95% CI, 2.22-119] vs HR, 17.7 [95% CI, 2.43-130];
      p = 1.0) mortality. There was no significant difference in sensitivity,
      specificity, negative predictive value, or positive predictive value. Axial and
      four-chamber measurements were well correlated (correlation coefficient, 0.857),
      and there was no significant difference in overall accuracy for predicting all
      cause (area under the curve [AUC], 0.582 vs 0.577; p = 0.72) and PE-related (AUC,
      0.743 vs 0.744; p = 1.0) mortality. CONCLUSION: The axial RV/LV diameter ratio is
      no less accurate than the reformatted four-chamber RV/LV diameter ratio for
      predicting 30-day mortality after PE.

PMID- 22623549
TI  - Screening CT colonography: multicenter survey of patient experience, preference,
      and potential impact on adherence.
AB  - OBJECTIVE: Prior research indicates CT colonography (CTC) would be a cost
      effective colorectal cancer (CRC) screening test if widespread availability were
      to increase overall CRC screening adherence rates. The primary aims of this
      multicenter study were to evaluate patient experience and satisfaction with CTC
      screening and compare preference against screening colonoscopy. MATERIALS AND
      METHODS: A 12-question survey instrument measuring pretest choice, experience,
      and satisfaction was given to a consecutive cohort of adults undergoing CTC
      screening in three disparate screening settings: university academic center,
      military medical center, and community practice. The study cohort was composed of
      individuals voluntarily participating in clinical CTC screening programs.
      RESULTS: A total of 1417 patients responded to the survey. The top reasons for
      choosing CTC for screening included "noninvasiveness" (68.0%), "avoidance of
      sedation/anesthesia" (63.1%), "ability to drive after the test" (49.2%),
      "avoidance of optical colonoscopy risks" (46.9%), and "identifying abnormalities
      outside the colon" (43.3%). Only 7.2% of patients reported pain during the CTC
      examination and only 2.5% reported greater than moderate discomfort. Of 441
      patients who had experienced both CTC and optical colonoscopy, 77.1% preferred
      CTC and 13.8% preferred optical colonoscopy. Of all patients, 29.6% indicated
      that they may not have undergone optical colonoscopy screening if CTC were not
      available. Of all patients, 92.9% labeled their overall experience with CTC as
      "excellent" or "good," and 93.0% indicated they would choose CTC for their next
      screening. CONCLUSION: Respondents reported a very high satisfaction level with
      CTC, and those who had experienced both modalities indicated a preference for CTC
      over optical colonoscopy. These results suggest that CTC has the potential to
      increase adherence to CRC screening guidelines if widely available.

PMID- 22623550
TI  - Factors involved in discrepant preliminary radiology resident interpretations of
      neuroradiological imaging studies: a retrospective analysis.
AB  - OBJECTIVE: The purpose of this article is to determine discrepancy rates in
      radiology residents' interpretations of CT and MRI studies of the head, neck, and
      spine and to attempt to quantify its potential or realized effect on patient
      care. Secondarily, we attempted to determine the effect of resident, study, and
      patient variables on discrepancy rate. MATERIALS AND METHODS: A retrospective
      review of all relevant studies from March 1, 2009, through December 31, 2009,
      revealed 5695 cases with preliminary interpretations made by on-call residents.
      Preliminary and final attending radiologists' reports were compared for
      concordance, and for all discrepant reports, electronic patient records were
      investigated for patient impact. Discrepancies were deemed minor or major
      depending on the presence of a negative impact on care. Variables were
      investigated for their effect on discrepancy rate by univariate logistic
      regression analysis, with significant regressors included in subsequent
      multivariate modeling. RESULTS: The overall discrepancy rate for all included
      studies was 8.4% (7.2% minor and 1.2% major). Head CT showed the highest
      concordance (92.6%), whereas MRI studies had discrepancy rates when compared with
      equivalent CT studies. By multivariate binomial logistic regression, several
      variables positively correlated with concordance, including resident training
      level, outpatient status, and concluding hours of call shift. CONCLUSION: The
      observed rates of discrepancy for all study types were comparable to those in the
      current literature. Furthermore, a nearly linear downward trend in discrepancy
      rate with increasing resident training level was found. Similarly, we uniquely
      showed that discrepancy rate varies with patient status, study indication, and
      hour of call. These factors should be appropriately considered during evaluation
      or remediation of radiology residents.

PMID- 22623551
TI  - Physician self-referral of lumbar spine MRI with comparative analysis of negative
      study rates as a marker of utilization appropriateness.
AB  - OBJECTIVE: Financial interest in imaging equipment may affect the imaging
      referral patterns of ordering physicians. The purpose of this article is to
      determine whether ownership of MRI equipment by ordering physicians predicts the
      likelihood and prevalence of positive findings on lumbar spine MRI as a metric
      for comparison of utilization. MATERIALS AND METHODS: A retrospective review was
      performed of 500 consecutive diagnostic lumbar spine MRI examinations in one
      radiology practice ordered by two separate referring physician groups serving the
      same geographic community: one with financial interest in the MRI equipment used
      (financial-interest group) and one without financial interest in the MRI
      equipment used (no-financial-interest group). Negative examinations and total
      number of lesions per positive study were recorded for each group. RESULTS: Five
      hundred scans met inclusion criteria during the study period (250 in the
      financial-interest group and 250 in the no-financial-interest group). The
      negative scan frequency was 86% higher in the financial-interest group (p <
      0.0001). Among positive scans, there was no significant difference in the average
      total number of positive lesions per scan (3.93 for the financial-interest group
      and 4.31 for the no-financial-interest group; p = 0.132). The average age of
      patients imaged by the financial-interest group was 49.8 years, versus 56.9 years
      for the no-financial-interest group (p < 0.0001). CONCLUSION: Lumbar spine MRI
      examinations referred by the financial-interest group were significantly more
      likely to be negative than those referred by the no-financial-interest group.
      Lesion frequency among positive scans suggests similar severity of disease
      between the two patient populations. Patients imaged by the financial-interest
      group were significantly younger than those imaged by the no-financial-interest
      group.

PMID- 22623552
TI  - Differentiation of kidney stones using dual-energy CT with and without a tin
      filter.
AB  - OBJECTIVE: The aim of this in vitro study was to examine the capability of three
      protocols of dual-energy CT imaging in distinguishing calcium oxalate, calcium
      phosphate, and uric acid kidney stones. MATERIALS AND METHODS: A total of 48
      calcium oxalate, calcium phosphate, and uric acid human kidney stone samples were
      placed in individual containers inside a cylindric water phantom and imaged with
      a dual-energy CT scanner using the following three scanning protocols of
      different combinations of tube voltage, with and without a tin filter: 80 and 140
      kVp without a tin filter, 100 and 140 kVp with a tin filter, and 80 and 140 kVp
      with a tin filter. The mean attenuation value (in Hounsfield units) of each stone
      was recorded in both low- and high-energy CT images in each protocol. The dual
      energy ratio of the mean attenuation values of each stone was computed for each
      protocol. RESULTS: For all three protocols, the uric acid stones were
      significantly different (p < 0.001) from the calciferous stones according to
      their dual-energy ratio values. For differentiating calcium oxalate and calcium
      phosphate stones, the difference between their dual-energy ratio values was
      statistically significant, with different degrees of significance (range, p <
      0.001 to p = 0.03) for all three protocols. On the basis of the values of the
      area under receiver operating characteristic curve (AUC) of calcified stone
      differentiation, the three protocols were ranked in the following order: the 80-
      and 140-kVp tin filter protocol (AUC, 0.996), the 100- and 140-kVp tin filter
      protocol (AUC, 0.918), and the 80- and 140-kVp protocol (AUC, 0.871). CONCLUSION:
      The tin filter added to the high-energy tube and the use of a wider dual-energy
      difference are important for improving the stone differentiation capability of
      dual-energy CT imaging.

PMID- 22623553
TI  - Can sarcoidosis and metastatic bone lesions be reliably differentiated on routine
      MRI?
AB  - OBJECTIVE: Sarcoidosis lesions revealed on MRI in the axial skeleton and long
      bones resemble osseous metastases, which can lead to a potentially significant
      misdiagnosis. We hypothesized that osseous sarcoidosis lesions could be
      differentiated from osseous metastases on MRI and sought to propose and evaluate
      features distinguishing these entities. MATERIALS AND METHODS: MR images obtained
      at 1.5 T of 34 subjects (22 with osseous metastatic disease, 12 with osseous
      sarcoidosis) with 79 single or multiple bone lesions (40 metastatic, 39
      sarcoidal) were reviewed independently by two blinded, experienced
      musculoskeletal radiologists. Fluid-sensitive and T1-weighted images were viewed
      separately. Proposed discriminating features were peri- or intralesional fat,
      specified border characteristics, and the presence of an extraosseous soft-tissue
      mass. An additional feature for spinal lesions was posterior element involvement.
      On the basis of these criteria, the readers provided a binary diagnosis and
      confidence score. RESULTS: The overall sensitivity for both readers was 46.3% and
      specificity, 97.4%. T1-weighted images were associated with higher sensitivity
      than T2-weighted images (59.0% vs 34.1%, respectively; p = 0.025) and with
      comparable specificity (97.6% vs 97.2%, p = 0.91). Diagnostic accuracy was higher
      using the discriminators of a mass or posterior element involvement for
      metastasis (83.3%) than border characteristics (68.0%) or lesion fat (65.0%) for
      sarcoidosis; the latter two features provided near 100% specificity but poor
      sensitivity (14.3% and 0%, respectively). Readers reported higher confidence
      diagnosing osseous sarcoidosis lesions than metastatic lesions, with a trend for
      higher confidence with T1-weighted images (p = 0.088). CONCLUSION: Osseous
      sarcoidosis lesions cannot be reliably distinguished from metastatic lesions on
      routine MRI studies by readers experienced in evaluating these lesions.

PMID- 22623554
TI  - MRI of aseptic lymphocytic vasculitis-associated lesions in metal-on-metal hip
      replacements.
AB  - OBJECTIVE: The aim of this review is to describe the clinical, histopathologic,
      and MRI features of aseptic lymphocytic vasculitis-associated lesions in total
      hip replacements. CONCLUSION: The introduction of modern metal-on-metal hip
      arthroplasty has been accompanied by a newly described disease, aseptic
      lymphocytic vasculitis-associated lesions, which is characterized histologically
      by bland necrosis and dense perivascular lymphocytic infiltrates. Conventional
      radiographic findings are often normal, but the typical MRI findings include
      periprosthetic fluid collections, soft-tissue masses, gluteal tendon avulsion,
      bone loss, periosteal stripping, neurovascular involvement, and periprosthetic
      fractures. The severity of the histologic and MRI appearances can be graded
      according to defined published criteria.

PMID- 22623555
TI  - Progression of corpus callosum diffusion-tensor imaging values during a period of
      signal changes consistent with myelination.
AB  - OBJECTIVE: Changes in signal intensity on T1- and T2-weighted MR images
      consistent with myelination in the corpus callosum occur during months 3-9 of
      postnatal life and occur earlier in the splenium than in the genu. We
      hypothesized that the rate of change in diffusion-tensor imaging parameters in
      the first year of life would be greater in the splenium, especially during months
      3-9. SUBJECTS AND METHODS: Fifty-two infants (age range, 0-52 weeks) underwent
      one MRI examination with a six-direction diffusion-tensor imaging sequence.
      Fractional anisotropy, apparent diffusion coefficient, radial diffusivity, and
      axial diffusivity were measured in the genu and splenium of the corpus callosum.
      For each parameter, the slopes of change in the splenium and in the genu were
      measured for the entire first year of life and for the age period 3-9 months. The
      ratios of slope of change in the splenium to that in the genu in these two
      periods were compared. RESULTS: For fractional anisotropy, the ratio of slope of
      change in the splenium to that in the genu was 1.67 in the first year and 4.00
      for 3-9 months; apparent diffusion coefficient, 2.00 in the first year and 4.33
      for 3-9 months; radial diffusivity, 1.75 in the first year and 4.40 for 3-9
      months; and axial diffusivity, 3.25 in the first year and 4.86 for 3-9 months.
      CONCLUSION: Rates of change were always greater in the splenium. For the age
      period 3-9 months, the splenium-to-genu ratio was approximately 1.5- to 2.5-fold
      as high as that for the entire year. These findings correspond well with the
      sequence of signal intensity changes in the corpus callosum.

PMID- 22623556
TI  - Correlating metabolic activity on 18F-FDG PET/CT with histopathologic
      characteristics of osseous and soft-tissue sarcomas: a retrospective review of
      136 patients.
AB  - OBJECTIVE: The objective of our study was to determine whether there is a
      statistically significant correlation between metabolic activity of osseous and
      soft-tissue sarcomas as measured by the maximum standardized uptake value
      (SUV(max)) on (18)F-FDG PET/CT and histopathologic characteristics such as
      mitotic counts, the presence of necrosis, and the presence of a myxoid component.
      MATERIALS AND METHODS: We retrospectively evaluated 238 consecutive patients with
      known soft-tissue or osseous sarcoma who underwent (18)F-FDG PET/CT for initial
      staging or assessment for recurrence of disease. The SUV(max) of each primary or
      of the most intense metastatic lesion was measured and was compared with the
      histologic data provided in the final pathology reports. RESULTS: Histopathologic
      data were available for 136 sarcomas. The median SUV(max) values of sarcomas with
      mitotic counts of less than 2.00 (per 10 high-power fields [HPF]), 2.00-6.99,
      7.00-16.24, and 16.25 or greater were 5.0, 6.6, 10.3, and 13.0, respectively (p =
      0.0003). The median SUV(max) for the sarcomas with necrosis (90 patients) was 8.6
      and for those without necrosis (43 patients), 6.0 (p = 0.026). The median
      SUV(max) for the sarcomas without a myxoid component (118 patients) was 7.7 and
      with a myxoid component (16 patients) was 6.2 (p = 0.28). CONCLUSION: There was a
      statistically significant correlation between the mitotic count and the SUV(max)
      as well as between the presence of tumor necrosis and the SUV(max). Although a
      correlation between the presence of a myxoid component and SUV(max) was shown, it
      was not found to be statistically significant. These findings improve on the
      current information in the literature regarding the use of PET/CT for guidance in
      sarcoma biopsy. Correlating the SUV(max) with histologic markers that also
      feature prominently in major sarcoma grading systems may help improve the
      accuracy of grading and of prognostication by allowing the SUV(max) to
      potentially serve as a surrogate marker in these grading systems, particularly in
      cases in which there is interobserver disagreement in the pathologic diagnosis or
      in cases in which the sarcoma cannot be properly classified on the basis of
      histopathologic evaluation alone.

PMID- 22623557
TI  - Feasibility of fast dynamic MRI for noninvasive monitoring during ectopic liver
      cell transplantation to the spleen in a porcine model.
AB  - OBJECTIVE: Liver cell transplantation is a promising approach for the treatment
      of metabolic liver disorders. However, a method for noninvasive monitoring during
      liver cell transplantation is not available clinically. The aim of this study was
      to investigate the feasibility of fast dynamic MRI monitoring during liver cell
      infusion to the spleen, which is considered an ectopic implantation site for
      liver cell transplantation. MATERIALS AND METHODS: Porcine liver cells were
      labeled with micron-sized iron oxide particles and infused to the spleens of pigs
      (n = 5) via the lineal artery. MRI was performed using a 3-T MR scanner.
      Initially, T1- and T2-weighted pulse sequences were tested. Thereafter, fast
      dynamic MRI was performed during cell infusion. MR findings were verified by
      immunohistological examinations. RESULTS: Images from static MRI (TR/TE,
      2500/105.2) showed significantly lower signal intensity and signal-to-noise ratio
      after cell infusion compared with pretransplant images. T2-weighted fast dynamic
      MRI enabled visualization of signal decrease of the spleen during cell infusion.
      When cells were infused systemically, no signal changes in the spleen were
      observed. CONCLUSION: This study shows that fast dynamic MRI can enable
      noninvasive monitoring during liver cell transplantation to the spleen. This
      approach could be useful for preclinical studies and for quality control of
      clinical liver cell transplantation.

PMID- 22623558
TI  - Ultrafast 3-T MRI in the evaluation of children with acute lower abdominal pain
      for the detection of appendicitis.
AB  - OBJECTIVE: The purpose of this study is to evaluate the feasibility of ultrafast
      3-T MRI in the evaluation of children with acute lower abdominal pain for the
      detection of appendicitis. SUBJECTS AND METHODS: Forty-two pediatric patients (30
      girls and 12 boys; mean age, 11.5 years; age range, 4-17 years) with acute
      abdominal pain were prospectively studied. Ultrafast 3-T MRI was performed with a
      three-plane single-shot turbo spin-echo sequence and an axial T2-weighted turbo
      spin-echo sequence with fat suppression. All scans were performed without
      sedation or oral or IV contrast agent. Scan times were less than 8 minutes 45
      seconds (median, 5 minutes 40 seconds). Patients underwent CT or ultrasound or
      both as a comparison study to the MRI examination. The MRI, CT, and ultrasound
      examinations were interpreted independently by four board-certified radiologists
      who were blinded to patient information, study interpretations, surgical
      pathologic findings, and final diagnosis. RESULTS: Twelve of 42 cases of acute
      appendicitis were detected with 100% sensitivity, 99% specificity, 100% negative
      predictive value, and 98% positive predictive value, all of which were
      statistically significant (p < 0.01). The pooled and individual receiver
      operating characteristic curves for radiologists' interpretation of the diagnosis
      of acute appendicitis were greater than 0.95 in all cases (p < 0.01) CONCLUSION:
      Ultrafast 3-T MRI is a feasible alternative imaging modality for the diagnosis of
      acute appendicitis in children, particularly in cases where ultrasound is
      equivocal or nondiagnostic, as an alternative to CT. Ultrafast MRI requires no
      sedation and no oral or IV contrast agent and has no associated radiation
      exposure risks.

PMID- 22623559
TI  - Pulmonary embolism detected by pulmonary MDCT angiography in older children and
      young adults: risk factor assessment.
AB  - OBJECTIVE: The purpose of this article is to determine the risk factors for
      pulmonary embolism (PE) among older children and young adults who underwent
      pulmonary CT angiography (CTA) for evaluation of clinically suspected PE.
      MATERIALS AND METHODS: We used our hospital information system to retrospectively
      identify all consecutive patients 19-25 years old who underwent pulmonary CTA for
      evaluation of clinically suspected PE between July 2004 and March 2011. Two
      experienced pediatric radiologists retrospectively and independently reviewed a
      series of 116 consecutive pulmonary CTA studies from this population. Each
      examination was reviewed for the presence of PE. Seven possible risk factors
      (immobilization, prior PE or deep venous thrombosis [DVT], cardiac disease,
      malignancy, hypercoagulable state, excess estrogen, and central venous line
      placement) were compared between patients with and without PE using univariate
      statistics, including Student t test and Pearson chi-square test. Multiple
      logistic regression modeling was used to identify independent risk factors for
      PE. Receiver operating characteristic curve analysis was applied to determine the
      optimal cutoff number of risk factors for predicting a pulmonary CTA result
      positive for PE. RESULTS: The study population consisted of 116 patients (34 men
      and 82 women; mean age, 20.7 +/- 1.8 years; range, 18.6-25.4 years) who underwent
      a total of 116 pulmonary CTA studies. Sixteen (14%) of 116 patients were found to
      have PE on pulmonary CTA. The level of involvement of PE was segmental in 16 of
      31 PEs (52%), lobar in eight (26%), subsegmental in five (16%), and main or
      central in two (6%). Three risk factors--immobilization (p < 0.001), history of
      prior PE or DVT (p = 0.001), and cardiac disease (p = 0.004)--were found to be
      significant independent risk factors for the presence of PE detected by pulmonary
      CTA. When two or more risk factors were used as the clinical threshold, the
      sensitivity for positive PE was 75% (12/16 patients) and the specificity was 99%
      (99/100 patients). CONCLUSION: The use of risk factor assessment as a first-line
      triage tool has the potential to guide more appropriate use of pulmonary CTA in
      this population, with potential associated reductions in radiation exposure and
      costs.

PMID- 22623560
TI  - Percutaneous radiofrequency ablation of hepatocellular carcinoma: fusion imaging
      guidance for management of lesions with poor conspicuity at conventional
      sonography.
AB  - OBJECTIVE: The purpose of this study was to determine whether fusion imaging
      guided percutaneous radiofrequency ablation (RFA) is effective in the management
      of hepatocellular carcinoma (HCC) that has poor conspicuity at conventional
      sonography. SUBJECTS AND METHODS: Percutaneous RFA of HCC with poor conspicuity
      was performed under fusion imaging guidance. The time needed for image fusion
      between the ultrasound and CT or MR images was recorded. The quality of image
      fusion and the degree of operator confidence in identifying the index tumor were
      graded on 4-point scales. Technical success and procedure-related complications
      were evaluated with liver CT immediately after RFA. RESULTS: Thirty patients with
      HCC (1.0 +/- 0.3 cm) were enrolled. Twenty-seven of the 30 lesions detected at
      planning ultrasound were identified with fusion imaging. Of the 30 HCC candidate
      lesions detected with ultrasound, five were found to be pseudolesions close to
      the index tumor. The time needed for image fusion for the 27 lesions was 3.7 +/-
      2.1 minutes (range, 1.3-9.0 minutes). The quality of image fusion was graded 3.4
      +/- 0.6, and the degree of operator confidence in identifying the 30 HCCs, 3.3 +/
      0.9. The technical success rate was 90% (27/30) in intention-to-treat analysis
      and 100% in analysis of actually treated lesions. There were no major RFA-related
      complications. CONCLUSION: Fusion imaging-guided percutaneous RFA is effective in
      the management of HCC that has poor ultrasound conspicuity.

PMID- 22623561
TI  - Unresectable pancreatic cancer: arterial embolization to achieve a single blood
      supply for intraarterial infusion of 5-fluorouracil and full-dose IV gemcitabine.
AB  - OBJECTIVE: Response rates to systemic chemotherapy for unresectable pancreatic
      cancer are low. The purposes of this phases 1 and 2 study of intraarterial
      therapy were to ascertain the recommended dose of intraarterial chemoinfusion and
      to evaluate the efficacy and safety of this therapy. SUBJECTS AND METHODS:
      Pancreatic arteries originating from the superior mesenteric artery (the anterior
      and posterior inferior pancreaticoduodenal and the dorsal pancreatic) were
      embolized to achieve a single blood supply from the celiac artery to manage
      pancreatic cancer, and a catheter-port system was placed. Intraarterial 5
      fluorouracil (5-FU) and IV gemcitabine (fixed dose of 1000 mg/m(2)) were
      administered. In phase 1, doses of 5-FU were increased from 750 to 1000 mg/m(2).
      In phase 2, tumor response, toxicity, and survival time were assessed. RESULTS: A
      total of 20 patients were enrolled. In 19 patients (95%), the technique to unify
      the pancreatic blood supply was successful. No severe toxicity was observed with
      escalation of the 5-FU dose. The tumor response rate was 68.8%. The median
      overall survival time was 9.8 months and the progression-free survival time, 6.0
      months. The grade 3 toxicities neutropenia (15.8%) and thrombocytopenia (5.3%)
      occurred. CONCLUSION: In intraarterial administration of 5-FU at a dose of 1000
      mg/m(2) combined with full-dose systemic gemcitabine for unresectable pancreatic
      cancer, the toxicity rate was acceptable, and response rate and survival time
      improved over those for treatment with gemcitabine alone.

PMID- 22623562
TI  - Early postoperative CT as a prognostic biomarker in patients with advanced
      ovarian, tubal, and primary peritoneal cancer deemed optimally debulked at
      primary cytoreductive surgery.
AB  - OBJECTIVE: The purpose of this article is to determine whether early
      postoperative CT provides prognostic information in patients with advanced
      ovarian, tubal, or primary peritoneal carcinoma with optimal debulking reported
      at primary cytoreduction. MATERIALS AND METHODS: Our study included 63 patients
      who underwent primary cytoreductive surgery for presumed advanced ovarian cancer,
      who had optimal debulking (residual disease <= 1 cm) reported at surgery, and who
      underwent CT before and 7-49 days after surgery. Two radiologists independently
      retrospectively interpreted all postoperative CT scans and scored lesions on a 5
      point scale, where 1 indicates normal and 5 indicates definitely malignant.
      Lesions larger than 1 cm with a CT score of 4 or 5 were considered suboptimally
      debulked residual disease. RESULTS: Suboptimally debulked residual disease on CT
      (range, 1.1-5.8 cm) was reported by reader 1 for 29 of 63 patients (46%) and by
      reader 2 for 31 of 63 patients (49%), with substantial interobserver agreement
      (kappa = 0.75). Patients with suboptimally debulked residual disease on CT had
      significantly worse median progression-free survival (p = 0.001, both readers)
      and overall survival (p <= 0.010, both readers). By univariate and multivariate
      analyses, suboptimally debulked residual disease on CT remained a significant
      independent predictor of progression-free survival (p = 0.001, both readers) and
      overall survival (p <= 0.006, both readers). CONCLUSION: Our study showed that
      residual disease larger than 1 cm was present on early postoperative CT in almost
      half of the patients deemed to have optimally debulked disease at primary
      cytoreduction. Residual disease larger than 1 cm detected on early postoperative
      CT was associated with significant decreases in both progression-free and overall
      survival.

PMID- 22623563
TI  - Necessity of hysterosalpingography after Essure microinsert placement for
      contraception.
AB  - OBJECTIVE: The objective of our study was to determine whether
      hysterosalpingography is necessary after Essure microinsert placement by
      evaluating the rates of appropriate placement and of satisfactory tubal occlusion
      in a general population. MATERIALS AND METHODS: We identified all patients who
      underwent hysterosalpingography after Essure microinsert placement for desired
      sterility between January 1, 2008, and August 1, 2010. We recorded demographic
      information and the hysterosalpingographic results. The images and operative
      reports of all cases with abnormal hysterosalpingographic findings were reviewed.
      The hysterosalpingographic results were reviewed for appropriate placement of the
      microinsert, for successful tubal occlusion, and for any additional
      abnormalities. We also reviewed the medical records for documentation of
      subsequent pregnancies. RESULTS: Two hundred forty hysterosalpingographic
      examinations were performed after 237 hysteroscopic microinsert placement
      procedures in 235 women. The mean age of the subjects was 35 years (range, 20-50
      years). Twenty-two examinations (9.2%) were abnormal. Fourteen (5.8%) revealed
      inappropriate placement: six with tubal occlusion, seven without tubal occlusion,
      and one with an indeterminate finding for tubal occlusion. Fifteen examinations
      (6.3%) showed tubal nonocclusion: Microinsert placement was inappropriate in
      seven cases and appropriate in eight. Of the 22 abnormal hysterosalpingographic
      examinations, 20 had operative reports available. Eleven (55%) described
      difficulties with device insertion. Forty-two endometrial abnormalities were
      described in hysterosalpingographic reports of 38 patients. One subsequent
      pregnancy was documented in a patient with satisfactory device placement and
      tubal occlusion on hysterosalpingography. CONCLUSION: Hysterosalpingography after
      Essure microinsert placement is necessary because 6.3% of examinations showed
      abnormalities requiring an alternative form of contraception.

PMID- 22623564
TI  - Patient follow-up after concordant histologically benign imaging-guided biopsy of
      MRI-detected lesions.
AB  - OBJECTIVE: The purpose of this study was to review the reported experience and
      suggest follow-up after biopsy for MRI-detected lesions. CONCLUSION: Imaging
      guided biopsy, using MRI or sonographic guidance, of MRI-detected lesions may
      result in false-negative results that are not appreciated at the time of the
      biopsy. A 6-month follow-up MRI is suggested as the most appropriate interval to
      identify lesions that were missed at biopsy without clinically significant delay
      in diagnosis of those lesions that are malignant.

PMID- 22623565
TI  - Solid pleural lesions.

PMID- 22623566
TI  - Flaps, slings, and other things: CT after reconstructive surgery--expected
      changes and detection of complications.
AB  - OBJECTIVE: This article will discuss the typical CT appearance of myocutaneous
      surgically placed flaps as well as some frequently encountered complications of
      this surgery. We will discuss the appearance of relatively new, but increasingly
      encountered, nonnative materials used in reconstructive surgery, such as spacers,
      bulking agents, hemostatic agents, and other reconstructive materials.
      CONCLUSION: Oncologic surgery often requires reconstruction using myocutaneous
      flaps. Therefore, an understanding of the type of reconstruction performed is
      important for the accuracy of postoperative radiologic interpretation to
      recognize presence of a flap to avoid misdiagnosis of tumor recurrence.

PMID- 22623567
TI  - Spectrum of imaging findings in Salmonella infections.
AB  - OBJECTIVE: Radiologic findings in Salmonella infections are not well described.
      In most patients, Salmonella infections produce mild and self-limiting clinical
      manifestations and therefore are treated empirically with antibiotics. Radiologic
      investigations are usually performed for patients with severe clinical
      manifestations or complications and for patients with unusual findings.
      CONCLUSION: This pictorial essay illustrates various imaging findings in culture
      proven cases of Salmonella infection, described broadly as common and uncommon
      manifestations.

PMID- 22623568
TI  - What the radiologist needs to know about urolithiasis: part 1--pathogenesis,
      types, assessment, and variant anatomy.
AB  - OBJECTIVE: This article reviews types of urinary calculi and their imaging
      appearances, presents direct and secondary imaging findings of urolithiasis, and
      provides an overview of treatment methods. Pertinent imaging findings that impact
      clinical management are highlighted. The implications of complex or variant
      genitourinary anatomy are reviewed. We outline a standard format for the
      reporting of urolithiasis to facilitate informed clinical management decisions.
      CONCLUSION: Unenhanced CT is the preferred examination for evaluation of
      urolithiasis because of its availability, ease of performance, and high
      sensitivity. An awareness of the important imaging findings to report allows
      appropriate and efficient therapy.

PMID- 22623569
TI  - What the radiologist needs to know about urolithiasis: part 2--CT findings,
      reporting, and treatment.
AB  - OBJECTIVE: This article reviews types of urinary calculi and their imaging
      appearances, presents direct and secondary imaging findings of urolithiasis, and
      provides an overview of treatment methods. Pertinent imaging findings that affect
      clinical management are highlighted. The implications of complex or variant
      genitourinary anatomy are reviewed. We outline a standard format for the
      reporting of urolithiasis to facilitate informed clinical management decisions.
      CONCLUSION: Unenhanced CT is the preferred examination for evaluation of
      urolithiasis because of its availability, ease of performance, and high
      sensitivity. An awareness of the important imaging findings to report allows
      appropriate and efficient therapy.

PMID- 22623570
TI  - Pneumocystis jiroveci pneumonia: high-resolution CT findings in patients with and
      without HIV infection.
AB  - OBJECTIVE: The purpose of this essay is to review the spectrum of high-resolution
      CT findings of Pneumocystis jiroveci pneumonia in immunocompromised patients with
      and without HIV infection. CONCLUSION: Pneumocystis jiroveci pneumonia is a
      common opportunistic infection affecting immunosuppressed patients. High
      resolution CT may be indicated for evaluation of immunosuppressed patients with
      suspected pneumonia and normal chest radiographic findings. The most common high
      resolution CT finding of Pneumocystis jiroveci pneumonia is diffuse ground-glass
      opacity. Consolidation, nodules, cysts, and spontaneous pneumothorax also can
      develop.

PMID- 22623572
TI  - Automated liver volumetry in orthotopic liver transplantation using multiphase
      acquisitions on MDCT.
AB  - OBJECTIVE: The aim of this study was to test a new automated hepatic volumetry
      technique by comparing the accuracies and postprocessing times of manual and
      automated liver volume segmentation methods in a patient population undergoing
      orthotopic liver transplantation so that liver volume could be determined on
      pathology as the standard of reference. CONCLUSION: Both manual and automated
      multiphase MDCT-based volume measurements were strongly correlated to liver
      volume (Pearson correlation coefficient, r = 0.87 [p < 0.0001] and 0.90 [p <
      0.0001], respectively). Automated multiphase segmentation was significantly more
      rapid than manual segmentation (mean time, 16 +/- 5 [SD] and 86 +/- 3 seconds,
      respectively; p = 0.01). Overall, automated liver volumetry based on multiphase
      CT acquisitions is feasible and more rapid than manual segmentation.

PMID- 22623573
TI  - Accuracy of MRI in the diagnosis of meniscal tears in older patients.
AB  - OBJECTIVE: The objective of our study was to determine the accuracy of MRI in
      diagnosing meniscal tears in older patients and the frequency with which abnormal
      MRI findings correlate with degeneration, fraying, and tears at arthroscopy.
      MATERIALS AND METHODS: Ninety-two patients 50 years old or older who had
      undergone knee MRI followed by knee arthroscopy within 6 months were selected.
      Menisci were graded on a 5-point scale: 1, definitely no tear; 2, probably no
      tear; 3, indeterminate or equivocal; 4, probably a tear; and 5, definitely a
      tear. Meniscal signal changes, meniscal surface morphology, and extrameniscal
      abnormalities were noted. Operative notes were reviewed, and the sensitivity and
      specificity of MRI results were calculated. RESULTS: For medial tears, MRI had a
      sensitivity and specificity of 0.91 and 0.94, respectively, when grade 5 was
      considered a tear, 0.96 and 0.76 when grades 4 and 5 were considered a tear, and
      0.99 and 0.47 when grades 3-5 were considered a tear. For lateral tears, MRI had
      a sensitivity and specificity of 0.73 and 0.91 when grade 5 was considered a
      tear, 0.88 and 0.80 when grades 4 and 5 were considered a tear, and 1.0 and 0.61
      when grades 3-5 were considered a tear. The positive predictive values (PPVs) of
      MRI for the medial meniscus were 99%, grade 5; 57%, grade 4; 29%, grade 3; 25%,
      grade 2; and 0%, grade 1. For the lateral meniscus, the PPVs of MRI were 76%,
      grade 5; 36%, grade 4; 19%, grade 3; and 0%, grades 1 and 2. CONCLUSION: The
      accuracy of MRI for diagnosing meniscal tears in older patients is high and
      similar to that in younger patients when only definitive findings are considered
      a tear. The specificity decreases if equivocal or probable findings are
      considered a tear.

PMID- 22623571
TI  - Web-based mammography audit feedback.
AB  - OBJECTIVE: Interpreting screening mammography accurately is challenging and
      requires ongoing education to maintain and improve interpretative skills.
      Recognizing this, many countries with organized breast screening programs have
      developed audit and feedback systems using national performance data to help
      radiologists assess and improve their skills. We developed and tested an
      interactive Website to provide screening and diagnostic mammography audit
      feedback with comparisons to national and regional benchmarks. MATERIALS AND
      METHODS: Radiologists who participate in three Breast Cancer Surveillance
      Consortium registries in the United States were invited during 2009 and 2010 to
      use a Website that provides tabular and graphical displays of mammography audit
      reports with comparisons to national and regional performance measures. We
      collected data about the use and perceptions of the Website. RESULTS: Thirty-five
      of 111 invited radiologists used the Website from one to five times in a year.
      The most popular measure was sensitivity for both screening and diagnostic
      mammography, whereas a table with all measures was the most visited page. Of the
      13 radiologists who completed the postuse survey, all found the Website easy to
      use and navigate, 11 found the benchmarks useful, and nine reported that they
      intended to improve a specific outcome measure that year. CONCLUSION: An
      interactive Website to provide customized mammography audit feedback reports to
      radiologists has the potential to be a powerful tool in improving interpretive
      performance. The conceptual framework of customized audit feedback reports can
      also be generalized to other imaging tests.

PMID- 22623574
TI  - Abbreviated MRI for patients presenting to the emergency department with hip
      pain.
AB  - OBJECTIVE: The objective of our study was to assess the diagnostic performance of
      two abbreviated hip MRI protocols--coronal STIR images only and coronal STIR with
      coronal T1-weighted images--as compared with a full hip MRI protocol in patients
      presenting to the emergency department (ED) with hip pain and negative
      radiographic findings. MATERIALS AND METHODS: The cohort included 385 patients
      (277 females, 108 males; mean age, 61 years; age range, 16-99 years) who
      underwent MRI within 1 month of negative radiographs obtained for ED evaluation
      of hip pain between January 2000 and March 2009. MR examinations were graded
      independently by two musculoskeletal fellowship-trained emergency radiologists
      for detection of fracture, avascular necrosis (AVN), and muscle injury in three
      subsets: coronal STIR images only; coronal STIR images and coronal T1-weighted
      images; and the full examination. RESULTS: MRI detected findings suspicious for
      fracture in 42% (162/385) of patients, for AVN in 9% (33/385), and for muscle
      injury in 35% (134/385). The sensitivity and specificity of STIR alone in raising
      concern for fracture was 99% (220/223) for both readers, with small incremental
      benefits of adding coronal T1-weighted images. For AVN, specificity was 100%
      (28/28) with STIR alone, but the addition of coronal T1-weighted images provided
      substantial benefit by increasing sensitivity from 85% (28/33) to 97% (32/33).
      For muscle injury, sensitivity and specificity exceeded 95% (128/134) for both
      abbreviated examinations. CONCLUSION: An abbreviated MRI protocol including
      coronal STIR and coronal T1-weighted images has high sensitivity and specificity
      for fracture, AVN, and muscle injury in ED patients presenting with hip pain and
      negative radiographs.

PMID- 22623575
TI  - Adhesive capsulitis of the shoulder: value of inferior glenohumeral ligament
      signal changes on T2-weighted fat-saturated images.
AB  - OBJECTIVE: The objective of our study was to evaluate the performance of MRI for
      the diagnosis of adhesive capsulitis using signal intensity changes of the
      inferior glenohumeral ligament on T2-weighted fat-saturated sequences. MATERIALS
      AND METHODS: MR images of 34 shoulders with a final clinical diagnosis of
      adhesive capsulitis were compared with those of an age-matched control group (34
      shoulders) with no clinical signs of adhesive capsulitis. MR images were acquired
      before and after IV injection of gadolinium and were evaluated by two readers.
      The T2 signal intensity at the inferior glenohumeral ligament, the thickness of
      the coracohumeral ligament, and whether there was obliteration of subcoracoid fat
      were evaluated on unenhanced images. Enhancement at the inferior glenohumeral
      ligament and enhancement at the rotator interval were evaluated on contrast
      enhanced images. The sensitivity, specificity, and interobserver variability of
      these signs were calculated. RESULTS: T2 hyperintensity of the inferior
      glenohumeral ligament showed a high sensitivity (85.3-88.2%) and high specificity
      (88.2%) for the diagnosis of adhesive capsulitis with excellent interobserver
      variability (kappa = 0.85). Signal analysis at the inferior glenohumeral ligament
      presented a higher sensitivity and a better interobserver agreement than the
      other signs of adhesive capsulitis evaluated. Gadolinium injection did not
      increase the performance of the inferior glenohumeral ligament signal analysis.
      An extracapsular hyperintense layer on T2-weighted images was identified as a new
      sign of adhesive capsulitis. CONCLUSION: T2 capsular signal intensity change
      offers a high performance for the diagnosis of adhesive capsulitis without the
      need for IV or intraarticular contrast injection.

PMID- 22623576
TI  - Diffusion-weighted imaging for differentiating benign from malignant skull
      lesions and correlation with cell density.
AB  - OBJECTIVE: The objective of our study was to determine the utility of diffusion
      weighted imaging (DWI) and cell density for differentiating benign from malignant
      skull lesions. MATERIALS AND METHODS: A retrospective review was performed.
      Minimum apparent diffusion coefficient (ADC) values were measured and normalized
      to white matter, which we refer to as "normalized ADC," in 24 skull lesions (12
      malignant and 12 benign) in 18 patients. In addition, cell densities were
      measured in 15 cases and correlated with ADC values. RESULTS: The average minimum
      ADC in malignant tumors was 0.70 * 10(-3) mm(2)/s versus 1.11 * 10(-3) mm(2)/s in
      benign tumors (p = 0.0037). Similarly, the average normalized ADC for malignant
      tumors was 1.03, whereas the average normalized ADC for benign tumors was 1.65 (p
      = 0.0012). Receiver operating characteristic curve analysis yielded optimal
      normalized ADC and ADC thresholds of 1.23 (accuracy, 84.6%; sensitivity, 75.0%;
      specificity, 92.3%) and 1.01 * 10(-3) mm(2)/s (accuracy, 83.7%; sensitivity,
      83.3%; specificity, 84.6%), respectively. There was a significant inverse
      correlation between cell density and normalized ADC (r = -0.58; p = 0.023). The
      low cellularity in chordoma and low-grade chondrosarcoma and high cellularity in
      eosinophilic granuloma may explain the DWI features of these lesions. CONCLUSION:
      ADC values in skull lesions correlate with cell density and can potentially
      narrow the differential diagnoses for indeterminate skull lesions. Understanding
      the histopathologic features of skull lesions can refine interpretation of DWI.

PMID- 22623577
TI  - Feasibility of mapping T2 relaxation time in the pediatric metacarpal head with a
      3-T MRI system.
AB  - OBJECTIVE: T2 relaxation time is sensitive in detecting early cartilage damage.
      There are few reports of T2 mapping for smaller joints because of technical
      challenges. The purpose of this study is to evaluate the feasibility of T2
      mapping of the metacarpal head cartilage in children. CONCLUSION: T2 mapping of
      the metacarpal head cartilage is feasible in children on a 3-T scanner with
      commercially available coils. An increase in the T2 values near the osteochondral
      junction likely reflects the secondary physis.

PMID- 22623578
TI  - Inferior vena cava filter-associated abnormalities: MDCT findings.
AB  - OBJECTIVE: Deep venous thrombosis from the pelvis or lower extremities has
      significant morbidity, and subsequent pulmonary embolism has a high mortality
      rate. Immediate anticoagulation in patients with deep venous thrombosis is
      crucial in preventing this lethal complication. However, in patients with
      contraindications for or failure of anticoagulation, inferior vena cava filters
      reduce mortality by decreasing the incidence of pulmonary embolism. CONCLUSION:
      In this review, we discuss the various pathologic abnormalities related to
      inferior vena cava filters, as seen on MDCT images.

PMID- 22623579
TI  - Comparison of 3- and 1.5-T dynamic breast MRI for visualization of spiculated
      masses previously identified using mammography.
AB  - OBJECTIVE: The purpose of this article is to determine the effectiveness of MRI
      for visualizing spiculated breast cancer lesions that were previously identified
      using mammography and to compare the diagnostic quality of 3- and 1.5-T dynamic
      MRI by assessing the visualization of spiculation in such lesions. MATERIALS AND
      METHODS: One hundred twenty MRI studies of breast cancers clearly identified as
      spiculated masses using mammography (71 MRI studies at 3 T that included both
      bilateral axial and unilateral sagittal images and 49 MRI studies at 1.5 T that
      included bilateral axial images only) were independently reviewed by three
      radiologists. The three different radiologists scored the visualization of the
      spiculation with respect to 3-T sagittal, 3-T axial, or 1.5-T axial images.
      RESULTS: The diagnostic quality of sagittal 3-T dynamic MRI studies, as
      determined by assessing the visualization of spiculation, was significantly
      better than that of axial 3-T (p = 0.009) and 1.5-T (p = 0.004) studies. For
      small (< 1 cm) lesions, the diagnostic quality of sagittal 3-T studies determined
      by assessing the visualization of spiculation was significantly better than that
      of axial 1.5-T studies (p = 0.029). CONCLUSION: Unilateral sagittal in-plane and
      through-plane high-spatial-resolution 3-T images can offer particularly higher
      spatial resolution for improved assessment of spiculation than do axial in-plane
      high-spatial-resolution images obtained at 1.5 and 3 T.

PMID- 22623580
TI  - Postbiopsy confirmation of MR-detected lesions biopsied using ultrasound.
AB  - OBJECTIVE: The purpose of this article is to outline a quick and effective method
      of confirming MR-sonographic correlation for lesions detected with MRI but
      percutaneously biopsied using ultrasound. CONCLUSION: Ensuring that a lesion seen
      on targeted ultrasound is the same as that detected at MRI can be difficult. For
      benign concordant lesions, a mismatch may only be discovered at 6-month
      postbiopsy MRI follow-up. However, lesion correlation can be established on the
      same day as biopsy by obtaining a single unenhanced T1-weighted non-fat-saturated
      pulse sequence just after percutaneous ultrasound-guided biopsy. Scanning time is
      less than 4 minutes. Postbiopsy changes and the biopsy clip are easily seen and
      help verify MR-sonographic lesion correlation.

PMID- 22623581
TI  - Entering unread or outside-read radiologic exams to a PACS.

PMID- 22623582
TI  - Is the radiologist responsible for administering sedation?

PMID- 22623583
TI  - Should we catch the train of shear-wave elastography?

PMID- 22623584
TI  - Intraductal papillary neoplasm of the bile ducts.

PMID- 22623585
TI  - Forensic and pathology remarks concerning the mummified fetuses of King
      Tutankhamun.

PMID- 22623586
TI  - Allosteric inhibition of Taspase1's pathobiological activity by enforced
      dimerization in vivo.
AB  - Taspase1 mediates cleavage of the mixed lineage leukemia (MLL) protein and
      leukemia-provoking MLL fusions and promotes solid malignancies. Currently, no
      effective and specific Taspase1 inhibitors are available, precluding its
      therapeutic exploitation. As the Taspase1 proenzyme is autoproteolytically
      cleaved and assumed to assemble into an active alphabetabetaalpha heterodimer, we
      attempted to interfere with its activity by targeting Taspase1's dimerization.
      Notably, enforced expression of inactive Taspase1 mutants, aiming to inhibit
      formation of active protease dimers, was not inhibitory. Immunoprecipitation, gel
      filtration, and in vivo protein interaction assays revealed that active Taspase1
      exists predominantly as an alphabeta monomer in living cells, providing an
      explanation why overexpression of inactive mutants was not trans-dominant. To
      alternatively test the biological consequences of enforced dimerization, we
      engineered Taspase1 variants containing the Jun/Fos dimerization motif. In
      absence of the respective interaction partners, the protease fusions were fully
      active, while enforcing dimerization by coexpression significantly inhibited
      processing of several target proteins in living cells. Our study provides the
      first evidence that Taspase1 is already active as an alphabeta monomer, arguing
      against heterocomplex formation being required for its pathobiological activity.
      Thus, it clearly supports strategies aiming to inhibit the cancer-promoting
      activity of Taspase1 by the identification of chemical decoys enforcing its
      dimerization.

PMID- 22623587
TI  - Grb10 regulates the development of fiber number in skeletal muscle.
AB  - Grb10 is an intracellular adaptor protein that acts as a negative regulator of
      insulin and insulin-like growth factor 1 (IGF1) receptors. Since global deletion
      of Grb10 in mice causes hypermuscularity, we have characterized the skeletal
      muscle physiology underlying this phenotype. Compared to wild-type (WT) controls,
      adult mice deficient in Grb10 have elevated body mass and muscle mass throughout
      adulthood, up to 12 mo of age. The muscle enlargement is not due to increased
      myofiber size, but rather an increase in myofiber number (142% of WT, P<0.01).
      There is no change in myofiber type proportions between WT and Grb10-deficient
      muscles, nor are the metabolic properties of the muscles altered on Grb10
      deletion. Notably, the weight and cross-sectional area of hindlimbs from neonatal
      mice are increased in Grb10-deficient animals (198 and 137% of WT, respectively,
      both P<0.001). Functional gene signatures for myogenic signaling and
      proliferation are up-regulated in Grb10-deficient neonatal muscle. Our findings
      indicate that Grb10 plays a previously unrecognized role in regulating the
      development of fiber number during murine embryonic growth. In addition, Grb10
      ablated muscle from adult mice shows coordinate gene changes that oppose those of
      muscle wasting pathologies, highlighting Grb10 as a potential therapeutic target
      for these conditions.

PMID- 22623588
TI  - Different domains in nidogen-1 and nidogen-2 drive basement membrane formation in
      skin organotypic cocultures.
AB  - Nidogen-1 and nidogen-2 are homologous proteins found in all basement membranes
      (BMs). They show comparable binding activities in vitro and partially redundant
      functions in vivo. Previously, we showed that in skin organotypic cocultures, BM
      formation was prevented in the absence of nidogens and that either nidogen was
      able to rescue this failure. We now dissected the two nidogens to identify the
      domains required for BM deposition. For that purpose, HaCaT cells were grown on
      collagen matrices containing nidogen-deficient, murine fibroblasts. After
      addition of nidogen-1 or nidogen-2 protein fragments comprising different binding
      domains, BM deposition was analyzed by immunofluorescence and electron
      microscopy. We could demonstrate that the rod-G3 domain of nidogen-2 was
      sufficient to achieve deposition of BM components at the epidermal-collagen
      interface. In contrast, for nidogen-1, both the G2 and G3 domains were required.
      Immunoblot analysis confirmed that all BM components were present in comparable
      amounts under all culture conditions. This finding demonstrates that nidogens,
      although homologous proteins, exert their effect on BM assembly through different
      binding domains, which may in turn result in alterations of BM structure and
      functions, thus providing an explanation for the phenotypical differences
      observed between nidogen-1 and -2 deficient mice.

PMID- 22623589
TI  - Foreword: Understanding and influencing multilevel factors across the cancer care
      continuum.

PMID- 22623590
TI  - Introduction: Understanding and influencing multilevel factors across the cancer
      care continuum.
AB  - Health care in the United States is notoriously expensive while often failing to
      deliver the care recommended in published guidelines. There is, therefore, a need
      to consider our approach to health-care delivery. Cancer care is a good example
      for consideration because it spans the continuum of health-care issues from
      primary prevention through long-term survival and end-of-life care. In this
      monograph, we emphasize that health-care delivery occurs in a multilevel system
      that includes organizations, teams, and individuals. To achieve health-care
      delivery consistent with the Institute of Medicine's six quality aims (safety,
      effectiveness, timeliness, efficiency, patient-centeredness, and equity), we must
      influence multiple levels of that multilevel system. The notion that multiple
      levels of contextual influence affect behaviors through interdependent
      interactions is a well-established ecological view. This view has been used to
      analyze health-care delivery and health disparities. However, experience
      considering multilevel interventions in health care is much less robust. This
      monograph includes 13 chapters relevant to expanding the foundation of research
      for multilevel interventions in health-care delivery. Subjects include clinical
      cases of multilevel thinking in health-care delivery, the state of knowledge
      regarding multilevel interventions, study design and measurement considerations,
      methods for combining interventions, time as a consideration in the evaluation of
      effects, measurement of effects, simulations, application of multilevel thinking
      to health-care systems and disparities, and implementation of the Affordable Care
      Act of 2010. Our goal is to outline an agenda to proceed with multilevel
      intervention research, not because it guarantees improvement in our current
      approach to health care, but because ignoring the complexity of the multilevel
      environment in which care occurs has not achieved the desired improvements in
      care quality outlined by the Institute of Medicine at the turn of the millennium.

PMID- 22623591
TI  - Multilevel factors affecting quality: examples from the cancer care continuum.
AB  - The complex environmental context must be considered as we move forward to
      improve cancer care and, ultimately, patient and population outcomes. The cancer
      care continuum represents several care types, each of which includes multiple
      technical and communication steps and interfaces among patients, providers, and
      organizations. We use two case scenarios to 1) illustrate the variability,
      diversity, and interaction of factors from multiple levels that affect care
      quality and 2) discuss research implications and provide hypothetical examples of
      multilevel interventions. Each scenario includes a targeted literature review to
      illustrate contextual influences upon care and sets the stage for theory-informed
      interventions. The screening case highlights access issues in older women, and
      the survivorship case illustrates the multiple transition challenges faced by
      patients, families, and organizations. Example interventions show the potential
      gains of implementing intervention strategies that work synergistically at
      multiple levels. While research examining multilevel intervention is a priority,
      it presents numerous study design, measurement, and analytic challenges.

PMID- 22623593
TI  - Embedding the examination of multilevel factors in an organization field context.

PMID- 22623594
TI  - In search of synergy: strategies for combining interventions at multiple levels.
AB  - The social ecological perspective provides a compelling justification for
      multilevel intervention. Yet, it offers little guidance for selecting
      interventions that work together in complementary or synergistic ways. Using a
      causal modeling framework, we describe five strategies for increasing potential
      complementarity or synergy among interventions that operate at different levels
      of influence: accumulation, amplification, facilitation, cascade, and
      convergence. We illustrate these strategies with examples of multilevel
      interventions to improve the quality of cancer treatment.

PMID- 22623592
TI  - State-of-the-art and future directions in multilevel interventions across the
      cancer control continuum.
AB  - We conducted literature searches and analyses to describe the current state of
      multilevel intervention (MLI) research and to identify opportunities to advance
      cancer control and prevention. We found single-level studies that considered
      other contextually important levels, and multilevel health-care systems research
      and community-wide studies. This literature is characterized by limited reporting
      of theoretical, contextual, temporal, and implementation factors. Most MLIs focus
      on prevention and screening, rather than diagnosis, treatment, or survivorship.
      Opportunities relate to 1) dynamic, adaptive emergent interventions and research
      designs that evolve over time by attending to contextual factors and interactions
      across levels; 2) analyses that include simulation modeling, or multimethod
      approaches that integrate quantitative and qualitative methods; and 3)
      translation and intervention approaches that locally reinvent MLIs in different
      contexts. MLIs have great potential to reduce cancer burden by using theory and
      integrating quantitative, qualitative, participatory, and transdisciplinary
      methods that continually seek alignment across intervention levels, pay attention
      to context, and adapt over time.

PMID- 22623595
TI  - Time issues in multilevel interventions for cancer treatment and prevention.
AB  - The concept of time introduces important complexities in estimating intervention
      effects, program and evaluation design, and measurement and analysis of
      individual change in multilevel interventions (MLIs). Despite growing recognition
      that time is a critical element for assessing both individual-level outcomes and
      higher-level changes in organizational, community, and policy contexts, most MLI
      designs and evaluations have not addressed these issues. In this chapter we
      discuss 1) conceptualizing disease life-course and treatment theory in MLIs, 2)
      approaches to incorporating time in research and program design for MLIs in
      cancer treatment and prevention, 3) analysis of time-varying multilevel data in
      the context of cancer treatment and prevention, and 4) resource considerations
      and trade-offs of incorporating time as a dimension of MLIs and analysis.
      Although analytic techniques for analyzing time-related phenomena are becoming
      more available and powerful, there has not been corresponding progress made in
      the development of theory to guide the application of these techniques in program
      design and implementation.

PMID- 22623596
TI  - Multilevel interventions: study design and analysis issues.
AB  - Multilevel interventions, implemented at the individual, physician, clinic,
      health-care organization, and/or community level, increasingly are proposed and
      used in the belief that they will lead to more substantial and sustained changes
      in behaviors related to cancer prevention, detection, and treatment than would
      single-level interventions. It is important to understand how intervention
      components are related to patient outcomes and identify barriers to
      implementation. Designs that permit such assessments are uncommon, however. Thus,
      an important way of expanding our knowledge about multilevel interventions would
      be to assess the impact of interventions at different levels on patients as well
      as the independent and synergistic effects of influences from different levels.
      It also would be useful to assess the impact of interventions on outcomes at
      different levels. Multilevel interventions are much more expensive and
      complicated to implement and evaluate than are single-level interventions. Given
      how little evidence there is about the value of multilevel interventions,
      however, it is incumbent upon those arguing for this approach to do multilevel
      research that explicates the contributions that interventions at different levels
      make to the desired outcomes. Only then will we know whether multilevel
      interventions are better than more focused interventions and gain greater
      insights into the kinds of interventions that can be implemented effectively and
      efficiently to improve health and health care for individuals with cancer. This
      chapter reviews designs for assessing multilevel interventions and analytic ways
      of controlling for potentially confounding variables that can account for the
      complex structure of multilevel data.

PMID- 22623597
TI  - Computational modeling and multilevel cancer control interventions.
AB  - This chapter presents an overview of computational modeling as a tool for
      multilevel cancer care and intervention research. Model-based analyses have been
      conducted at various "beneath the skin" or biological scales as well as at
      various "above the skin" or socioecological levels of cancer care delivery. We
      review the basic elements of computational modeling and illustrate its
      applications in four cancer control intervention areas: tobacco use, colorectal
      cancer screening, cervical cancer screening, and racial disparities in access to
      breast cancer care. Most of these models have examined cancer processes and
      outcomes at only one or two levels. We suggest ways these models can be expanded
      to consider interactions involving three or more levels. Looking forward, a
      number of methodological, structural, and communication barriers must be overcome
      to create useful computational models of multilevel cancer interventions and
      population health.

PMID- 22623599
TI  - Conducting multilevel intervention research: leveraging and looking beyond
      methodological advances.

PMID- 22623598
TI  - Multilevel interventions: measurement and measures.
AB  - BACKGROUND: Multilevel intervention research holds the promise of more accurately
      representing real-life situations and, thus, with proper research design and
      measurement approaches, facilitating effective and efficient resolution of health
      care system challenges. However, taking a multilevel approach to cancer care
      interventions creates both measurement challenges and opportunities. METHODS: One
      thousand seventy two cancer care articles from 2005 to 2010 were reviewed to
      examine the state of measurement in the multilevel intervention cancer care
      literature. Ultimately, 234 multilevel articles, 40 involving cancer care
      interventions, were identified. Additionally, literature from health services,
      social psychology, and organizational behavior was reviewed to identify measures
      that might be useful in multilevel intervention research. RESULTS: The vast
      majority of measures used in multilevel cancer intervention studies were
      individual level measures. Group-, organization-, and community-level measures
      were rarely used. Discussion of the independence, validity, and reliability of
      measures was scant. DISCUSSION: Measurement issues may be especially complex when
      conducting multilevel intervention research. Measurement considerations that are
      associated with multilevel intervention research include those related to
      independence, reliability, validity, sample size, and power. Furthermore,
      multilevel intervention research requires identification of key constructs and
      measures by level and consideration of interactions within and across levels.
      Thus, multilevel intervention research benefits from thoughtful theory-driven
      planning and design, an interdisciplinary approach, and mixed methods measurement
      and analysis.

PMID- 22623600
TI  - Health reforms as examples of multilevel interventions in cancer care.
AB  - To increase access and improve system quality and efficiency, President Obama
      signed the Patient Protection and Affordable Care Act with sweeping changes to
      the nation's health-care system. Although not intended to be specific to cancer,
      the act's implementation will profoundly impact cancer care. Its components will
      influence multiple levels of the health-care environment including states,
      communities, health-care organizations, and individuals seeking care. To
      illustrate these influences, two reforms are considered: 1) accountable care
      organizations and 2) insurance-based reforms to gather evidence about
      effectiveness. We discuss these reforms using three facets of multilevel
      interventions: 1) their intended and unintended consequences, 2) the importance
      of timing, and 3) their implications for cancer. The success of complex health
      reforms requires understanding the scientific basis and evidence for carrying out
      such multilevel interventions. Conversely and equally important, successful
      implementation of multilevel interventions depends on understanding the political
      setting and goals of health-care reform.

PMID- 22623601
TI  - Implementation and spread of interventions into the multilevel context of routine
      practice and policy: implications for the cancer care continuum.
AB  - The promise of widespread implementation of efficacious interventions across the
      cancer continuum into routine practice and policy has yet to be realized.
      Multilevel influences, such as communities and families surrounding patients or
      health-care policies and organizations surrounding provider teams, may determine
      whether effective interventions are successfully implemented. Greater recognition
      of the importance of these influences in advancing (or hindering) the impact of
      single-level interventions has motivated the design and testing of multilevel
      interventions designed to address them. However, implementing research evidence
      from single- or multilevel interventions into sustainable routine practice and
      policy presents substantive challenges. Furthermore, relatively few multilevel
      interventions have been conducted along the cancer care continuum, and fewer
      still have been implemented, disseminated, or sustained in practice. The purpose
      of this chapter is, therefore, to illustrate and examine the concepts underlying
      the implementation and spread of multilevel interventions into routine practice
      and policy. We accomplish this goal by using a series of cancer and noncancer
      examples that have been successfully implemented and, in some cases, spread
      widely. Key concepts across these examples include the importance of phased
      implementation, recognizing the need for pilot testing, explicit engagement of
      key stakeholders within and between each intervention level; visible and
      consistent leadership and organizational support, including financial and human
      resources; better understanding of the policy context, fiscal climate, and
      incentives underlying implementation; explication of handoffs from researchers to
      accountable individuals within and across levels; ample integration of multilevel
      theories guiding implementation and evaluation; and strategies for long-term
      monitoring and sustainability.

PMID- 22623604
TI  - Multilevel intervention research applications in cancer care delivery.

PMID- 22623603
TI  - Multilevel research and the challenges of implementing genomic medicine.
AB  - Advances in genomics and related fields promise a new era of personalized
      medicine in the cancer care continuum. Nevertheless, there are fundamental
      challenges in integrating genomic medicine into cancer practice. We explore how
      multilevel research can contribute to implementation of genomic medicine. We
      first review the rapidly developing scientific discoveries in this field and the
      paucity of current applications that are ready for implementation in clinical and
      public health programs. We then define a multidisciplinary translational research
      agenda for successful integration of genomic medicine into policy and practice
      and consider challenges for successful implementation. We illustrate the agenda
      using the example of Lynch syndrome testing in newly diagnosed cases of
      colorectal cancer and cascade testing in relatives. We synthesize existing
      information in a framework for future multilevel research for integrating genomic
      medicine into the cancer care continuum.

PMID- 22623605
TI  - Summary of the multilevel interventions in health care conference.

PMID- 22623602
TI  - Multilevel interventions and racial/ethnic health disparities.
AB  - To examine the impact of multilevel interventions (with three or more levels of
      influence) designed to reduce health disparities, we conducted a systematic
      review and meta-analysis of interventions for ethnic/racial minorities (all
      except non-Hispanic whites) that were published between January 2000 and July
      2011. The primary aims were to synthesize the findings of studies evaluating
      multilevel interventions (three or more levels of influence) targeted at ethnic
      and racial minorities to reduce disparities in their health care and obtain a
      quantitative estimate of the effect of multilevel interventions on health
      outcomes among these subgroups. The electronic database PubMed was searched using
      Medical Subject Heading terms and key words. After initial review of abstracts,
      26 published studies were systematically reviewed by at least two independent
      coders. Those with sufficient data (n = 12) were assessed by meta-analysis and
      examined for quality using a modified nine-item Physiotherapy Evidence Database
      coding scheme. The findings from this descriptive review suggest that multilevel
      interventions have positive effects on several health behavior outcomes,
      including cancer prevention and screening, as well improving the quality of
      health-care system processes. The weighted average effect size across studies for
      all health behavior outcomes reported at the individual participant level (k =
      17) was odds ratio (OR) = 1.27 (95% confidence interval [CI] = 1.11 to 1.44); for
      the outcomes reported by providers or organizations, the weighted average effect
      size (k = 3) was OR = 2.53 (95% CI = 0.82 to 7.81). Enhanced application of
      theories to multiple levels of change, novel design approaches, and use of
      cultural leveraging in intervention design and implementation are proposed for
      this nascent field.

PMID- 22623606
TI  - Multilevel intervention research: lessons learned and pathways forward.
AB  - This summary reflects on this monograph regarding multilevel intervention (MLI)
      research to 1) assess its added value; 2) discuss what has been learned to date
      about its challenges in cancer care delivery; and 3) identify specific ways to
      improve its scientific soundness, feasibility, policy relevance, and research
      agenda. The 12 submitted chapters, and discussion of them at the March 2011
      multilevel meeting, were reviewed and discussed among the authors to elicit key
      findings and results addressing the questions raised at the outset of this
      effort. MLI research is underrepresented as an explicit focus in the cancer
      literature but may improve implementation of studies of cancer care delivery if
      they assess contextual, organizational, and environmental factors important to
      understanding behavioral and/or system-level interventions. The field lacks a
      single unifying theory, although several psychological or biological theories are
      useful, and an ecological model helps conceptualize and communicate
      interventions. MLI research designs are often complex, involving nonlinear and
      nonhierarchical relationships that may not be optimally studied in randomized
      designs. Simulation modeling and pilot studies may be necessary to evaluate MLI
      interventions. Measurement and evaluation of team and organizational
      interventions are especially needed in cancer care, as are attention to the
      context of health-care reform, eHealth technology, and genomics-based medicine.
      Future progress in MLI research requires greater attention to developing and
      supporting relevant metrics of level effects and interactions and evaluating MLI
      interventions. MLI research holds an unrealized promise for understanding how to
      improve cancer care delivery.

PMID- 22623607
TI  - Epilogue.

PMID- 22623608
TI  - Development of PCR primer sets for intron 1 of the low-copy gene LEAFY in
      Davalliaceae.
AB  - PREMISE OF THE STUDY: Primers were designed for amplifying intron 1 of the single
      copy nuclear LEAFY gene for species of Davalliaceae. METHODS AND RESULTS: New
      primer sets were designed and successfully amplified for intron 1 of the LEAFY
      gene in 13 species representing the five genera of Davalliaceae. The orthology of
      these sequences was further confirmed by phylogenetic analyses. Site variation in
      LEAFY intron 1 sequences across genera of the Davalliaceae and among accessions
      of the Humata repens complex were 18% and 8%, respectively. Such variation was
      greater than that for the cpDNA atpB-rbcL intergenic spacer region across the
      same taxa and accessions. CONCLUSIONS: Using our newly designed primers, intron 1
      of the LEAFY gene could be amplified for all species tested. In addition, this
      single-copy, biparentally inherited, and quickly evolving region showed
      considerable potential for addressing infraspecific-level questions.

PMID- 22623609
TI  - Development of thallus axes in Usnea longissima (Parmeliaceae, Ascomycota), a
      fruticose lichen showing diffuse growth.
AB  - PREMISE OF THE STUDY: While cell wall thickening in plants is generally
      associated with tissue maturation, fungal tissues in at least two lichens
      continue to grow extensively while accumulating massively thickened cell walls.
      We examined Usnea longissima to determine how diffuse growth shapes morphological
      and anatomical development of thallus axes and how the highly thickened cell
      walls of the central cord behave in diffuse growth. METHODS: Fresh material was
      examined with light and epifluorescence microscopy and conventional and low
      temperature SEM. Fixed material was embedded in Spurr's resin, microtome
      sectioned, and examined with TEM and light microscopy. KEY RESULTS: Main axes
      consisted essentially of bare medullary cord tissue; their characteristic
      morphology developed by destruction of the overlying cortex and consequent
      stimulation of lateral branch formation. Fungal cells of the cord tissue
      continually deposited wall layers of electron-transparent substances and layered,
      electron-dense materials that include UV-epifluorescent components.
      Discontinuities were evident in the outermost layers; new branch cells grew
      through wall materials accumulated by older neighboring cells. CONCLUSIONS:
      Sustained diffuse growth of cord tissue in U. longissima underlies the structural
      transformation of a corticated thallus branch into a long axis. In the cord
      tissue, diffuse growth may be responsible for the increasingly disrupted
      appearance of the older, electron-dense cell wall layers, while new wall
      materials are laid down adjacent to the protoplast. Cell and tissue development
      appeared comparable to that observed previously in Ramalina menziesii, although
      accumulation of wall material was somewhat less extensive and with a greater
      proportion of electron-dense/UV-epifluorescent components.

PMID- 22623610
TI  - A lower Cretaceous (Valanginian) seed cone provides the earliest fossil record
      for Picea (Pinaceae).
AB  - PREMISE OF STUDY: Sequence analyses for Pinaceae have suggested that extant
      genera diverged in the late Mesozoic. While the fossil record indicates that
      Pinaceae was highly diverse during the Cretaceous, there are few records of
      living genera. This description of an anatomically preserved seed cone extends
      the fossil record for Picea A. Dietrich (Pinaceae) by ~75 Ma. METHODS: The
      specimen was collected from the Apple Bay locality of Vancouver Island (Lower
      Cretaceous, Valanginian) and is described from anatomical sections prepared using
      cellulose acetate peels. Cladistic analyses of fossil and extant pinaceous seed
      cones employed parsimony ratchet searches of an anatomical and morphological
      matrix. KEY RESULTS: This new seed cone has a combination of characters shared
      only with the genus Picea A. Dietr. and is thus described as Picea burtonii
      Klymiuk et Stockey sp. nov. Bisaccate pollen attributable to Picea is found in
      the micropyles of several ovules, corroborating the designation of this cone as
      an early spruce. Cladistic analyses place P. burtonii with extant Picea and an
      Oligocene representative of the genus. Furthermore, our analyses indicate that
      Picea is sister to Cathaya Chun et Kuang, and P. burtonii helps to establish a
      minimum date for this node in hypotheses of conifer phylogeny. CONCLUSIONS: As an
      early member of the extant genus Picea, this seed cone extends the fossil record
      of Picea to the Valanginian Stage of the Early Cretaceous, ca. 136 Ma, thereby
      resolving a ghost lineage predicted by molecular divergence analyses, and offers
      new insight into the evolution of Pinaceae.

PMID- 22623611
TI  - Isolation and characterization of microsatellite markers from Tiarella polyphylla
      (Saxifragaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for Tiarella
      polyphylla in Korea and Japan to study the genetic diversity and genetic
      structure of the species. METHODS AND RESULTS: We successfully isolated a total
      of nine polymorphic simple sequence repeat loci. These nine loci contained from
      two to eight alleles per locus. The observed and expected heterozygosities ranged
      from 0.000 to 0.250 and 0.000 to 0.974, respectively. CONCLUSIONS: The markers
      developed in this study may be used to estimate genetic diversity, genetic
      structure, and historical and recent gene flow in T. polyphylla, which requires
      conservation and management.

PMID- 22623612
TI  - A comparison of leaf crystal macropatterns in the two sister genera Piper and
      Peperomia (Piperaceae).
AB  - PREMISE OF THE STUDY: This is the first large-scale study comparing leaf crystal
      macropatterns of the species-rich sister genera Piper and Peperomia. It focuses
      on identifying types of calcium oxalate crystals and their macropatterns in
      leaves of both genera. The Piper results are placed in a phylogenetic context to
      show evolutionary patterns. This information will expand knowledge about crystals
      and provide specific examples to help study their form and function. One example
      is the first-time observation of Piper crystal sand tumbling in chlorenchyma
      vacuoles. METHODS: Herbarium and fresh leaves were cleared of cytoplasmic content
      and examined with polarizing microscopy to identify types of crystals and their
      macropatterns. Selected hydrated herbarium and fresh leaf punches were processed
      for scanning electron microscopy and x-ray elemental analysis. Vibratome sections
      of living Piper and Peperomia leaves were observed for anatomical features and
      crystal movement. KEY RESULTS: Both genera have different leaf anatomies. Piper
      displays four crystal types in chlorenchyma-crystal sand, raphides, styloids, and
      druses, whereas Peperomia displays three types-druses, raphides, and prisms.
      Because of different leaf anatomies and crystal types between the genera,
      macropatterns are completely different. Crystal macropattern evolution in both is
      characterized by increasing complexity, and both may use their crystals for light
      gathering and reflection for efficient photosynthesis under low-intensity light
      environments. CONCLUSIONS: Both genera have different leaf anatomies, types of
      crystals and crystal macropatterns. Based on Piper crystals associated with
      photosynthetic tissues and low-intensity light, further study of their function
      and association with surrounding chloroplasts is warranted, especially active
      crystal movement.

PMID- 22623613
TI  - Development of microsatellite markers in Parakmeria nitida (Magnoliaceae).
AB  - PREMISE OF THE STUDY: We developed microsatellite makers for Parakmeria nitida to
      investigate its population structure and conservation genetics. METHODS AND
      RESULTS: A total of 25 microsatellite primer pairs were developed using the Fast
      Isolation by AFLP of Sequences COntaining repeats (FIASCO) protocol, and
      polymorphism was assessed in three natural populations of P. nitida. Among these
      markers, 11 were monomorphic and 14 showed polymorphism. CONCLUSIONS: These
      markers are potentially useful for future population genetic analyses of P.
      nitida and will serve as an important tool for conservation efforts.

PMID- 22623614
TI  - More than half of individual health plans offer coverage that falls short of what
      can be sold through exchanges as of 2014.
AB  - The Affordable Care Act creates state-based health exchanges that will begin
      acting as a market place for health insurance plans and consumers in 2014. This
      paper compares the financial protection offered by today's group and individual
      plans with the standards that will apply to insurance sold in state-based
      exchanges. Some states may apply these standards to all health insurance sold
      within the state. More than half of Americans who had individual insurance in
      2010 were enrolled in plans that would not qualify as providing essential
      coverage under the rules of the exchanges in 2014. These people were enrolled in
      plans with an actuarial value below 60 percent, which means that the plans
      covered less than that proportion of the enrollees' health expenses. Many of
      today's individual health plans are below the "bronze" level, the lowest level of
      plan that can be sold through exchanges. In contrast, most group plans in 2010
      had an actuarial benefit of 80-89 percent and would qualify as highly rated
      "gold" plans in the exchanges. To sell to ten million new buyers on the
      exchanges, insurers will need to redesign benefit packages. Combined with a ban
      on medical underwriting, the individual insurance market in a post-health reform
      world will sharply contrast with the market of past decades.

PMID- 22623615
TI  - Delivery by caesarean section and risk of obesity in preschool age children: a
      prospective cohort study.
AB  - OBJECTIVE: To examine whether delivery by caesarean section is a risk factor for
      childhood obesity. DESIGN: Prospective prebirth cohort study (Project Viva).
      SETTING: Eight outpatient multi-specialty practices based in the Boston,
      Massachusetts area. PARTICIPANTS: We recruited women during early pregnancy
      between 1999 and 2002, and followed their children after birth. We included 1255
      children with body composition measured at 3 years of age. MAIN OUTCOME MEASURES:
      BMI score, obesity (BMI for age and sex >=95th percentile), and sum of triceps
      plus subscapular skinfold thicknesses at 3 years of age. RESULTS: 284 children
      (22.6%) were delivered by caesarean section. At age 3, 15.7% of children
      delivered by caesarean section were obese compared with 7.5% of children born
      vaginally. In multivariable logistic and linear regression models adjusting for
      maternal prepregnancy BMI, birth weight, and other covariates, birth by caesarean
      section was associated with a higher odds of obesity at age 3 (OR 2.10, 95% CI
      1.36 to 3.23), higher mean BMI z-score (0.20 units, 95% CI 0.07 to 0.33), and
      higher sum of triceps plus subscapular skinfold thicknesses (0.94 mm, 95% CI 0.36
      to 1.51). CONCLUSIONS: Infants delivered by caesarean section may be at increased
      risk of childhood obesity. Further studies are needed to confirm our findings and
      to explore mechanisms underlying this association.

PMID- 22623616
TI  - Systematic review and narrative synthesis of the effectiveness of contraceptive
      service interventions for young people, delivered in health care settings.
AB  - A systematic review and narrative synthesis to determine the effectiveness of
      contraception service interventions for young people delivered in health care
      premises was undertaken. We searched 12 key health and medical databases,
      reference lists of included papers and systematic reviews and cited reference
      searches on included articles. All retrieved literature was screened at title and
      abstract levels, and relevant articles were taken through to full paper
      appraisal. Data relating to study design, outcomes and quality were extracted by
      one reviewer and independently checked by a second reviewer. We included
      interventions that consisted of contraceptive service provision for young people,
      and also interventions to encourage young people to use existing contraceptive
      services. The searches identified 23 studies that met the inclusion criteria. The
      papers focused on: new adolescent services, outreach to existing services,
      advanced provision of emergency contraception, condom/contraceptive provision and
      advice and repeat pregnancy prevention. The literature in general is not well
      developed in terms of good quality effectiveness studies and key outcome
      measures. However, it is possible to make recommendations in terms of outreach
      versus targeted young people's services in health care settings, advanced
      provision of emergency contraception and long-acting reversible contraception to
      prevent repeat adolescent pregnancy.

PMID- 22623617
TI  - Factors influencing hand washing behaviour in primary schools: process evaluation
      within a randomized controlled trial.
AB  - This article explores factors that may influence hand washing behaviour among
      pupils and staff in primary schools. A qualitative process evaluation within a
      cluster randomized controlled trial included pupil focus groups (n = 16, aged 6
      11 years), semi-structured interviews (n = 16 teachers) and observations of hand
      washing facilities (n = 57). Pupils and staff in intervention and control schools
      demonstrated a similar level of understanding of how, when and why they should
      wash their hands. Lack of time, poor adult modelling of regular hand washing and
      unattractive facilities were seen as important barriers to regular hand washing.
      Reminders and explanations for the importance of hand hygiene were thought to
      have a positive impact. Influencing individual choices about hand washing through
      education and information may be necessary, but not sufficient, for initiating
      and maintaining good hand washing practices. Structural factors, including having
      time to wash hands using accessible, clean facilities, and being encouraged
      through the existence of hand washing opportunities in the daily routine and hand
      washing being viewed as the social norm, will also influence hand washing
      behaviour. The effectiveness of educational interventions at improving hand
      hygiene in primary schools may be improved by changing priorities of staff and
      increasing accessibility to quality facilities.

PMID- 22623618
TI  - Boosters, anyone? Exploring the added value of booster sessions in a self
      management intervention.
AB  - The current study explored the benefits of adding booster sessions to a validated
      and successful self-management intervention for type 2 diabetes patients (i.e.
      Beyond Good Intentions). Although the addition of booster sessions to self
      management interventions is often recommended, it has not been empirically
      established to what extent booster sessions are in fact appreciated by
      participants. Participants in the current study (N = 129) followed the Beyond
      Good Intentions program and were offered a series of three booster sessions at 1,
      3 and 5 months afterwards. Primary outcome variables included participants'
      attendance and evaluations of the booster phase. In addition, self-management
      behavior was assessed at baseline (T1), after the initial phase (T2) and after
      the booster phase (T3). Results showed that more than one-fourth of participants
      who completed the initial phase dropped out during the booster phase, and those
      who did complete both phases evaluated the booster phase significantly less
      positive as compared to the initial phase. With regard to the behavioral
      outcomes, we replicated previous findings showing positive effects on all
      measures during the initial phase. The booster phase, however, did not result in
      further improvements. It was concluded that the added value of booster sessions
      was, at best, questionable.

PMID- 22623620
TI  - FOXL2 is regulated during the bovine estrous cycle and its expression in the
      endometrium is independent of conceptus-derived interferon tau.
AB  - FOXL2, a winged-helix/forkhead domain transcription factor, is a key gene
      involved in the differentiation and biological functions of the ovary. In a
      recent transcriptomic analysis, we found that FOXL2 expression in bovine
      caruncular endometrium was different from that in intercaruncular endometrium. In
      order to gain new insights into FOXL2 in this tissue, we determined the
      expression of this transcription factor during the estrous cycle and the
      establishment of pregnancy in cattle. The endometrial expression of FOXL2 did not
      vary during maternal recognition of pregnancy (Days 16-20). Using an in vivo
      bovine model and primary cell cultures, we showed that FOXL2 was not an
      interferon-tau target gene. Both FOXL2 transcript and protein were expressed from
      Day 5 to Day 20 of the estrous cycle, and their levels showed a significant
      increase during the luteolytic phase. A 2-day progesterone supplementation in
      heifers led to a clear down-regulation of FOXL2 protein levels, suggesting the
      negative impact of progesterone on FOXL2 expression. Immunohistochemistry data
      revealed the localization of FOXL2 in endometrial stromal and glandular cells.
      FOXL2 subcellular distribution was shown to be nuclear in endometrial samples
      collected during the luteolytic period, while it was not detected in nuclei
      during the luteal phase and at implantation. Collectively, our findings provide
      the first evidence that FOXL2 is involved in the regulation of endometrial tissue
      physiology.

PMID- 22623619
TI  - Contextualizing an expanded definition of health literacy among adolescents in
      the health care setting.
AB  - The current emphasis on preventive health care and wellness services suggests
      that measures of skills and competencies needed to effectively navigate the
      health care system need to be better defined. We take an expanded perspective of
      health literacy and define it as a set of skills used to organize and apply
      health knowledge, attitudes and practices relevant when managing one's health
      environment. It is an emerging area of inquiry especially among adults and those
      with chronic conditions; however, it has been less studied among adolescent
      populations. To begin operationalizing this concept in a manner appropriate for
      teens in a health systems context, we explored knowledge, attitudes and practices
      related to health and preventive health care in 12 focus groups with publicly
      insured adolescents (N = 137), aged 13-17 years, as well as eight key informant
      interviews with physicians who serve publicly insured teens. Five dimensions
      emerged that provide a preliminary framework for an expanded definition of health
      literacy among adolescents. These include: (i) navigating the system, (ii) rights
      and responsibilities, (iii) preventive care, (iv) information seeking and (v)
      patient-provider relationship. This robust definition of health literacy
      contextualizes the concept in a health environment where individuals must be
      informed and skilled health care consumers.

PMID- 22623621
TI  - Connexin 31 (GJB3) deficiency in mouse trophoblast stem cells alters giant cell
      differentiation and leads to loss of oxygen sensing.
AB  - The nonphysiological placental oxidative environment has been implicated in many
      complications during human pregnancy. Oxygen tension can influence a broad
      spectrum of molecular changes leading to alterations in trophoblast cell lineage
      development. In this study, we report that mouse wild-type trophoblast stem cells
      (TSCs) react to low oxygen (3%) with an enhanced differentiation into the giant
      cell pathway, indicated by a downregulation of the early stem cell markers Eomes
      and Cdx2 as well as by a significant upregulation of Tfap2c and the
      differentiation markers Tpbpa and Prl3d1. Here we demonstrated that connexin
      31/GJB3-deficient TSCs failed to stabilize HIF-1A under low oxygen, resulting in
      nonresponsiveness of different marker genes, such as Cdx2 and Eomes and Tfap2c
      and Tpbpa. Moreover, connexin 31-deficient TSCs revealed a shift in giant cell
      differentiation from Prl3d1 expressing parietal giant cells to Ctsq, Prl3b1, and
      Prl2c2-positive giant cells, probably sinusoidal and canal lining trophoblast
      giant cells. Thus, loss of connexin 31 led to different giant cell subtypes which
      bypass the progenitor regulators Tfap2c and Tpbpa under low oxygen conditions.

PMID- 22623622
TI  - Amphibian oocytes release heat shock protein A during spawning: evidence for a
      role in fertilization.
AB  - Heat shock proteins A (HSPAs, previously known as HSP70s) are widely distributed
      proteins originally linked with heat shock but now associated with several normal
      cellular functions. We recently found indirect evidence suggesting a role for
      HSPAs in sperm-oocyte interaction in the amphibian Bufo arenarum. In the present
      study our aim was to study its expression, subcellular distribution, and role
      during fertilization. By Western blot analysis using two different antibodies we
      detected HSPAs present in B. arenarum oocytes in the absence of any stress. We
      performed two-dimensional electrophoresis and detected two isoforms with
      isoelectric points of 5.25 and 5.45. We studied its subcellular distribution
      isolating total membranes, cytosol, and plasma membranes. HSPAs were present in
      all of these fractions. We confirmed these results by immunofluorescence
      microscopy and also found that the HSPA signal was present in the vitelline
      envelope. To further test this, we performed Western blot analysis in isolated
      vitelline envelopes and in egg water (diffusible material from deposited
      oocytes). HSPAs were present in these two fractions. Moreover, human recombinant
      his-tagged HSPA (HSPA1A) was able to specifically bind to sperm in vitro
      (midpiece) and enhance sperm membrane integrity. In vitro fertilization assays in
      the presence of anti-HSPA polyclonal antibodies showed diminished fertilization
      scores at low sperm concentrations (10(5) cells per milliliter). Our results
      suggest that HSPAs are present in intracellular and extracellular structures of
      nonstressed B. arenarum oocytes and participates in fertilization by and that
      their release during spawning plays a role in sperm membrane integrity.

PMID- 22623623
TI  - Androgen initiates Sertoli cell tight junction formation in the hypogonadal (hpg)
      mouse.
AB  - Sertoli cell tight junctions (TJs) form at puberty as a major component of the
      blood-testis barrier (BTB), which is essential for spermatogenesis. This study
      characterized the hormonal induction of functional Sertoli cell TJ formation in
      vivo using the gonadotropin-deficient hypogonadal (hpg) mouse that displays
      prepubertal spermatogenic arrest. Androgen actions were determined in hpg mice
      treated for 2 or 10 days with dihydrotestosterone (DHT). Follicle-stimulating
      hormone (FSH) actions were studied in hpg mice expressing transgenic human FSH
      (hpg+tgFSH) with or without DHT treatment. TJ formation was examined by mRNA
      expression and immunolocalization of TJ proteins claudin-3 and claudin-11, and
      barrier functionality was examined by biotin tracer permeability.
      Immunolocalization of claudin-3 and claudin-11 was extensive at wild-type (wt)
      Sertoli cell TJs, which functionally excluded permeability tracer. In contrast,
      seminiferous tubules of hpg testes lacked claudin-3, but claudin-11 protein was
      present in adluminal regions of Sertoli cells. Biotin tracer permeated throughout
      these tubules, demonstrating dysfunctional TJs. In hpg+tgFSH testes, claudin-3
      was generally absent, but claudin-11 had redistributed basally toward the TJs,
      where function was variable. In hpg testes, DHT treatment stimulated the
      redistribution of claudin-11 protein toward the basal region of Sertoli cells by
      Day 2, increased Cldn3 and Cldn11 mRNA expression, then induced the formation of
      functional TJs containing both proteins by Day 10. In hpg+tgFSH testes, TJ
      protein redistribution was accelerated and functional TJs formed by Day 2 of DHT
      treatment. We conclude that androgen stimulates initial Sertoli cell TJ formation
      and function in mice, whereas FSH activity is insufficient alone, but augments
      androgen-induced TJ function.

PMID- 22623625
TI  - Mapping of novel peptides of WT-1 and presenting HLA alleles that induce epitope
      specific HLA-restricted T cells with cytotoxic activity against WT-1(+)
      leukemias.
AB  - The Wilms tumor protein (WT-1) is widely recognized as a tumor antigen that is
      expressed differentially by several malignancies. However, WT-1 peptides known to
      induce tumoricidal T cells are few. In the present study, we evaluated T-cell
      responses of 56 healthy donors to in vitro sensitization with autologous APCs
      loaded with a pool of overlapping 15-mer peptides spanning the sequence of WT-1.
      Thereafter, we mapped the WT-1 peptides eliciting responses in each individual,
      defined the immunogenic peptides, and identified their presenting HLA alleles. We
      report 41 previously unreported epitopes of WT-1: 5 presented by class II and 36
      by class I alleles, including 10 that could be presented by more than 1 class I
      allele. IFNgamma(+) T cells responding to 98% of the class I and 60% of the class
      II epitopes exhibited HLA-restricted cytotoxicity against peptide-loaded targets.
      T cells specific for 36 WT-1 peptides were evaluable for leukemocidal activity,
      of which 27 (75%) lysed WT-1(+) leukemic targets sharing their restricting HLA
      allele. Each epitope identified induced T-cell responses in most donors sharing
      the epitopes' presenting allele; these responses often exceeded responses to
      flanking peptides predicted to be more immunogenic. This series of immunogenic
      epitopes of WT-1 should prove useful for immunotherapies targeting WT-1(+)
      malignancies.

PMID- 22623626
TI  - A comparison of the combined ultrasound of the mediastinum by use of a single
      ultrasound bronchoscope versus ultrasound bronchoscope plus ultrasound
      gastroscope in lung cancer staging: a prospective trial.
AB  - OBJECTIVES: The aim of the study was to compare diagnostic utility of combined
      (i.e. transbronchial and transoesophageal) ultrasound imaging with needle biopsy
      of the mediastinum in lung cancer (LC) staging, (a) by use of a single ultrasound
      bronchoscope (CUSb) and (b) by using two scopes (CUS). METHODS: In consecutive LC
      patients, clinical stage IA-IIIB the CUS or CUSb was performed under mild
      sedation and, if negative, underwent lung resection with confirmatory systematic
      lymph node dissection. RESULTS: From 214 LC patients, 110 underwent CUS and 104
      underwent CUSb (618 biopsies); both revealed metastases in 50% of cases. There
      was 'minimal N2' in 11 of 14 false negative patients. Diagnostic sensitivity,
      specificity, accuracy, positive predictive value (PPV) and negative predictive
      value (NPV) of CUS was 91.7%, 98%, 94.6%, 98.2% and 90.7% respectively and of
      CUSb was 85%, 93.2%, 88.5%, 94.4%, 82%, respectively with no significant
      difference in yield of CUS vs CUSb (P = 0.255 and P = 0.192). The mean time of
      CUS (25 +/- 4.4 min) was significantly longer as compared to CUSb (14.9 +/- 2.3
      min) (P < 0.001). No severe complications of either method were observed.
      CONCLUSIONS: The combined ultrasound imaging of the mediastinum by use of CUSb is
      significantly less time-consuming and equally as effective and safe as the use of
      CUS for LC staging.

PMID- 22623628
TI  - A bioresorbable osteosynthesis device can induce an earlier sternal fusion after
      median sternotomy.
AB  - OBJECTIVES: We examined the impact of the bioresorbable osteosynthesis sternal
      pin (Super Fixsorb 30) on sternal healing after median sternotomy. METHODS: Sixty
      three patients who underwent aortic surgery through median sternotomy between
      January 2006 and March 2009 were analysed. Sternal pins were utilized in 36
      patients in addition to the standard closure of the sternum with Ethibond sutures
      (Group A), and 27 patients received no pins with the standard Ethibond sternal
      closure (Group B). The occurrence of transverse sternal dehiscence, anterior
      posterior displacement and complete fusion of the sternum were evaluated by a
      computed tomography scan. The cross-sectional cortical bone density area (CBDA)
      of the sternum was examined to evaluate the osteoconductivity of the sternal pin
      over a 12-month period. RESULTS: There was no sternal displacement (0%) observed
      in Group A at discharge. Meanwhile, five displacements (18.5%) were observed in
      Group B (P = 0.007). The complete sternal fusion rates at 12 months
      postoperatively were 100% in Group A, and 21.6% in Group B (P < 0.001). A
      significant increase in the CBDA was observed in Group A (P < 0.001; between CBDA
      at discharge and 12 months postoperatively). CONCLUSIONS: The Super Fixsorb 30
      sternal pin reduced an anterior-posterior sternal displacement and facilitated an
      earlier sternal fusion. The pin may have the potential to promote osteogenesis.

PMID- 22623627
TI  - Use of prothrombin complex concentrate for excessive bleeding after cardiac
      surgery.
AB  - OBJECTIVES: Prothrombin complex concentrates (PCCs) are sometimes used as 'off
      label' for excessive bleeding after cardiopulmonary bypass (CPB). The main
      objective of this study was to retrospectively evaluate the clinical and
      biological efficacy of PCC in this setting. METHODS: We reviewed the charts of
      all patients who had undergone cardiac surgery under CPB in our institution for 2
      years. Patients treated for active bleeding with haemostatic therapy were
      identified. Chest tube blood loss was quantified postoperatively in the first 24
      h. Coagulation parameters were recorded at intensive care unit admission and in
      the patient's first 24 h. Thromboembolic complications were also ascertained.
      RESULTS: Seventy-seven patients out of the 677 studied (11.4%) were included: PCC
      was solely administered in 24 patients (group I), fresh frozen plasma in 26
      (group II) and both in 27 (group III). The mean dose of PCC was 10.0 UI/kg +/-
      3.5 for group I vs 14.1 UI/kg +/- 11.2 for group III (P = 0.09). Initial blood
      loss in the first hour was different between the three groups (P = 0.05): 224 +/-
      131 ml for group I, 369 +/- 296 ml for group II and 434 +/- 398 ml for group III.
      Only group I vs group III presented a significant difference (P = 0.02).
      Variations of blood loss over time were no different according to the treatment
      groups (P = 0.12). Reductions in blood loss expressed in percentage showed no
      difference between the three groups after 2 h: 54.5% (68.6-30.8) for group I;
      45.0% (81.6-22.2) for group II; 57.6 (76.0-2.1) for group III; (P = 0.89). Re
      exploration for bleeding involved 1 patient in group I (4%), 2 in group II (8%)
      and 10 in group III (37%) (P = 0.002). Except for fibrinogen, variations of
      prothrombin time, activated partial thromboplastin time and platelets with time
      were not different according to the treatment groups. Cerebral infarction
      occurred in one patient in group II. CONCLUSIONS: Administration of low-dose of
      PCC significantly decreased postoperative bleeding after CPB.

PMID- 22623629
TI  - Antibiotic stewardship and early discharge from hospital: impact of a structured
      approach to antimicrobial management.
AB  - OBJECTIVES: To assess the impact of an infection team review of patients
      receiving antibiotics in six hospitals across the UK and to establish the
      suitability of these patients for continued care in the community. METHODS: An
      evaluation audit tool was used to assess all patients on antibiotic treatment on
      acute wards on a given day. Clinical and antibiotic use data were collected by an
      infection team (doctor, nurse and antibiotic pharmacist). Assessments were made
      of the requirement for continuing antibiotic treatment, route and duration
      [including intravenous (iv)/oral switch] and of the suitability of the patients
      for discharge from hospital and their requirement for community support. RESULTS:
      Of 1356 patients reviewed, 429 (32%) were on systemic antibiotics, comprising 165
      (38%) on iv +/- oral antibiotics and 264 (62%) on oral antibiotics alone. Ninety
      nine (23%) patients (including 26 on iv antibiotics) had their antibiotics
      stopped immediately on clinical grounds. The other 330 (77%) patients (including
      139 on iv antibiotics) needed to continue antibiotics, although 47 (34%) could be
      switched to oral. Eighty-nine (21%) patients were considered eligible for
      discharge, comprising 10 who would have required outpatient parenteral antibiotic
      therapy (OPAT), 55 who were suitable for oral outpatient treatment and 24 who had
      their antibiotics stopped. CONCLUSIONS: Infection team review had a significant
      impact on antimicrobial use, facilitating iv to oral switch and a reduction in
      the volume of antibiotic use, possibly reducing the risk of healthcare-associated
      complications and infections. It identified many patients who could potentially
      have been managed in the community with appropriate resources, saving 481 bed
      days. The health economics are reported in a companion paper.

PMID- 22623630
TI  - Antibiotic management and early discharge from hospital: an economic analysis.
AB  - OBJECTIVES: To evaluate potential costs and savings from implementing an
      evaluation tool that uses bedside review of antibiotic use and infection
      management to assess whether patients with infections in acute medical and
      surgical wards could have their antibiotic regimen changed and be safely managed
      out of hospital. METHODS: The tool was implemented in 30 acute wards in five UK
      hospital trusts. Data were collected on demographic variables, diagnosis, social
      situation, hospital stay and all current antibiotic prescribing for 291 patients.
      A physician and pharmacist assessed antibiotic therapy and feasibility of
      discharge. Resource use was measured for each patient, unit costs attached, and
      mean and total costs of implementing recommendations were calculated. RESULTS:
      Implementation of these recommendations could reduce total inpatient days by 494
      at a saving of L186 731, and save L20 215 from adjustment of antibiotic therapy.
      Additional costs were associated with implementation of the assessment (L2468),
      community support (L6227) and outpatient parenteral antimicrobial therapy
      (L5616). As a result, the net potential savings would be L192 635 in total or
      L662 (95% CI: L393, L930) for every patient assessed. Excluding eight patients
      with the highest potentially avoidable inpatient stays (>15 days), mean savings
      would fall to L363 per patient assessed but remain highly significant (95% CI:
      L261, L465). CONCLUSIONS: Careful assessment of antibiotic use in acute wards has
      the potential to reduce the use and cost of antibiotics, and length of stay.
      Added costs of assessment and out-of-hospital support services would offset a
      small proportion of these potential savings. Randomized studies are now needed to
      test these results.

PMID- 22623631
TI  - Prescribing strong opioids for pain in adult palliative care: summary of NICE
      guidance.

PMID- 22623633
TI  - Blepharitis.

PMID- 22623632
TI  - Association of onset to balloon and door to balloon time with long term clinical
      outcome in patients with ST elevation acute myocardial infarction having primary
      percutaneous coronary intervention: observational study.
AB  - OBJECTIVE: To evaluate the relation of symptom onset to balloon time and door to
      balloon time with long term clinical outcome in patients with ST segment
      elevation myocardial infarction (STEMI) having primary percutaneous coronary
      intervention. DESIGN: Observation of large cohort of patients with acute
      myocardial infarction. SETTING: 26 tertiary hospitals in Japan. PARTICIPANTS:
      3391 patients with STEMI who had primary percutaneous coronary intervention
      within 24 hours of symptom onset. MAIN OUTCOME MEASURES: Composite of death and
      congestive heart failure, compared by onset to balloon time and door to balloon
      time. RESULTS: Compared with an onset to balloon time greater than 3 hours, a
      time of less than 3 hours was associated with a lower incidence of a composite of
      death and congestive heart failure (13.5% (123/964) v 19.2% (429/2427), P<0.001;
      relative risk reduction 29.7%). After adjustment for confounders, a short onset
      to balloon time was independently associated with a lower risk of the composite
      endpoint (adjusted hazard ratio 0.70, 95% confidence interval 0.56 to 0.88;
      P=0.002). However, no significant difference was found in the incidence of a
      composite of death and congestive heart failure between the two groups of
      patients with short (<=90 minutes) and long (>90 minutes) door to balloon time
      (16.7% (270/1671) v 18.4% (282/1720), P=0.54; relative risk reduction 9.2%).
      After adjustment for confounders, no significant difference was seen in the risk
      of the composite endpoint between the two groups of patients with short and long
      door to balloon time (adjusted hazard ratio: 0.98, 0.78 to 1.24: P=0.87). A door
      to balloon time of less than 90 minutes was associated with a lower incidence of
      a composite of death and congestive heart failure in patients who presented
      within 2 hours of symptom onset (11.9% (74/883) v 18.1% (147/655), P=0.01;
      relative risk reduction 34.3%) but not in patients who presented later (19.7%
      (196/788) v 18.7% (135/1065), P=0.44; -5.3%). Short door to balloon time was
      independently associated with a lower risk of a composite of death and congestive
      heart failure in patients with early presentation (adjusted hazard ratio 0.58,
      0.38 to 0.87; P=0.009) but not in patients with delayed presentation (1.57, 1.12
      to 2.18; P=0.008). A significant interaction was seen between door to balloon
      time and time to presentation (interaction P=0.01). CONCLUSIONS: Short onset to
      balloon time was associated with better 3 year clinical outcome in patients with
      STEMI having primary percutaneous coronary intervention, whereas the benefit of
      short door to balloon time was limited to patients who presented early. Efforts
      to minimise onset to balloon time, including reduction of patient related delay,
      should be recommended to improve clinical outcome in STEMI patients.

PMID- 22623634
TI  - Hospital volume and patient outcomes after cholecystectomy in Scotland:
      retrospective, national population based study.
AB  - OBJECTIVES: To define associations between hospital volume and outcomes following
      cholecystectomy, after adjustment for case mix using a national database. DESIGN:
      Retrospective, national population based study using multilevel modelling and
      simulation. SETTING: Locally validated administrative dataset covering all NHS
      hospitals in Scotland. PARTICIPANTS: All patients undergoing cholecystectomy
      between 1 January 1998 and 31 December 2007. MAIN OUTCOME MEASURES: Mortality, 30
      day reoperation rate, 30 day readmission rate, and length of stay. RESULTS: We
      identified 59,918 patients who had a cholecystectomy in one of 37 hospitals: five
      hospitals had high volumes (>244 cholecystectomies/year), 10 had medium volumes
      (173-244), and 22 had low volumes (<173). Compared with low and medium volume
      hospitals, high volume hospitals performed more procedures non-electively (17.1%
      and 19.5% v 32.8%), completed more procedures laparoscopically (64.7% and 73.8% v
      80.9%), and used more operative cholangiography (11.2% and 6.3% v 21.2%; chi(2)
      test, all P<0.001). In a well performing multivariable analysis with bias
      correction for a low event rate, the odds ratio for death was greater in both the
      low volume (odds ratio 1.45, 95% confidence interval 1.06 to 2.00, P=0.022) and
      medium volume (1.52, 1.11 to 2.08, P=0.010) groups than in the high volume group.
      However, in simulation studies, absolute risk differences between volume groups
      were clinically negligible for patients with average risk (number needed to treat
      to harm, low v high volume, 3871, 1963 to 17,118), but were significant in
      patients with higher risk. In models accounting for the hierarchical structure of
      patients in hospitals, those in medium volume hospitals were more likely to
      undergo reoperation (odds ratio 1.74, 1.31 to 2.30, P<0.001) or be readmitted
      (1.17, 1.04 to 1.31, P=0.008) after cholecystectomy than those in high volume
      hospitals. Length of stay was shorter in high volume hospitals than in low
      (hazard ratio for discharge 0.78, 0.76 to 0.79, P<0.001) or medium volume
      hospitals (0.75, 0.74 to 0.77, P<0.001). These differences were also only of
      clinical significance in patients at higher risk. CONCLUSIONS: There is wide
      variation among hospitals in the management of gallstone disease and an
      association between higher hospital volume and better outcome after a
      cholecystectomy. The relative risk of death is lower in high volume centres, and
      although absolute risk differences between volume groups are significant for
      elderly patients and patients with comorbidity, they are clinically negligible
      for those at average risk.

PMID- 22623635
TI  - Can behavioural economics make us healthier?
AB  - Behavioural economics is becoming increasingly popular as a way to improve public
      health. George Loewenstein and colleagues point out some of the pitfalls and warn
      that it cannot be used as a substitute for conventional policies to tackle
      fundamental problems.

PMID- 22623636
TI  - Trusts can improve care by engaging their staff better, says think tank.

PMID- 22623638
TI  - Television shows and education about sexually transmitted infections: no laughing
      matter.

PMID- 22623639
TI  - Curious anatomys.

PMID- 22623640
TI  - Olympics' public health surveillance scheme will be retained after games, agency
      says.

PMID- 22623641
TI  - IVF is cost effective up to age 43, says NICE.

PMID- 22623642
TI  - NHS could save L170m by improving diabetes care, estimates watchdog.

PMID- 22623643
TI  - Restless legs syndrome.

PMID- 22623644
TI  - Israel extends the right to use a surrogate to gay and single people.

PMID- 22623645
TI  - Safer sport, shock treatment, stroke care, and safety triumph at the BMJ Group
      Awards 2012.

PMID- 22623646
TI  - The essential role of PIM kinases in sarcoma growth and bone invasion.
AB  - PIM kinases are a family of serine/threonine kinases composed of three different
      isoforms (PIM1, PIM 2 and PIM 3) that are highly homologous. Their expression is
      mediated by the JAK/STAT signalling pathway, providing survival and cell cycle
      transition signals. PIM kinases are heavily targeted for anticancer drug
      discovery. However, very little is known about the relative contribution of the
      different isoforms to the tumourigenesis process in vivo, and how their
      individual inhibition might affect tumour growth. Taking advantage of genetically
      modified mice, we explored whether the inhibition of specific isoforms is
      required to prevent sarcomas induced by 3-methylcholanthrene carcinogenic
      treatment. We found that absence of Pim2 and Pim3 greatly reduced sarcoma growth
      to a similar extent to the absence of all three isoforms. This model of sarcoma
      generally produces bone invasion by the tumour cells. Lack of Pim2 and Pim3
      reduced tumour-induced bone invasion by 70%, which is comparable with the
      reduction of tumour-induced bone invasion in the absence of all three isoforms.
      Similar results were obtained in mouse embryonic fibroblasts (MEFs) derived from
      these knockout (KO) mice, where double Pim2/3 KO MEFs already showed reduced
      proliferation and were resistant to oncogenic transformation by the RAS oncogene.
      Our data also suggest an important role of Gsk3beta phosphorylation in the
      process of tumourigenesis.

PMID- 22623647
TI  - A transcriptomics-based in vitro assay for predicting chemical genotoxicity in
      vivo.
AB  - The lack of accurate in vitro assays for predicting in vivo toxicity of chemicals
      together with new legislations demanding replacement and reduction of animal
      testing has triggered the development of alternative methods. This study aimed at
      developing a transcriptomics-based in vitro prediction assay for in vivo
      genotoxicity. Transcriptomics changes induced in the human liver cell line HepG2
      by 34 compounds after treatment for 12, 24, and 48 h were used for the selection
      of gene-sets that are capable of discriminating between in vivo genotoxins (GTX)
      and in vivo nongenotoxins (NGTX). By combining transcriptomics with publicly
      available results for these chemicals from standard in vitro genotoxicity
      studies, we developed several prediction models. These models were validated by
      using an additional set of 28 chemicals. The best prediction was achieved after
      stratification of chemicals according to results from the Ames bacterial gene
      mutation assay prior to transcriptomics evaluation after 24h of treatment. A
      total of 33 genes were selected for discriminating GTX from NGTX for Ames
      positive chemicals and 22 for Ames-negative chemicals. Overall, this method
      resulted in 89% accuracy and 91% specificity, thereby clearly outperforming the
      standard in vitro test battery. Transcription factor network analysis revealed
      HNF3a, HNF4a, HNF6, androgen receptor, and SP1 as main factors regulating the
      expression of classifiers for Ames-positive chemicals. Thus, the classical
      bacterial gene mutation assay in combination with in vitro transcriptomics in
      HepG2 is proposed as an upgraded in vitro approach for predicting in vivo
      genotoxicity of chemicals holding a great promise for reducing animal
      experimentations on genotoxicity.

PMID- 22623648
TI  - Vitamin D status at breast cancer diagnosis: correlation with tumor
      characteristics, disease outcome, and genetic determinants of vitamin D
      insufficiency.
AB  - We correlated serum 25-hydroxyvitamin D(3) (25OHD) levels with tumor
      characteristics and clinical disease outcome in breast cancer patients and
      assessed the impact of genetic determinants of vitamin D insufficiency. We
      collected serum from 1800 early breast cancer patients at diagnosis, measured
      25OHD by radioimmunoassay (RIA), and determined genetic variants in vitamin D
      related genes by Sequenom. Multivariable regression models were used to correlate
      25OHD levels with tumor characteristics. Cox proportional hazard models were used
      to assess overall survival (OS), disease-specific survival (DSS), and disease
      free interval (DFI). Lower 25OHD serum levels significantly correlated with
      larger tumor size at diagnosis (P = 0.0063) but not with lymph node invasion,
      receptor status, or tumor grade. Genetic variants in 25-hydroxylase (CYP2R1) and
      vitamin D-binding (DBP) protein significantly determined serum 25OHD levels but
      did not affect the observed association between serum 25OHD and tumor size. High
      serum 25OHD (>30 ng/mL) at diagnosis significantly correlated with improved OS (P
      = 0.0101) and DSS (P = 0.0192) and additionally had a modest effect on DFI, which
      only became apparent after at least 3 years of follow-up. When considering
      menopausal status, serum 25OHD had a strong impact on breast cancer-specific
      outcome in postmenopausal patients [hazards ratios for 25OHD >30 ng/mL versus
      <=30 ng/mL were 0.15 (P = 0.0097) and 0.43 (P = 0.0172) for DSS and DFI,
      respectively], whereas no association could be demonstrated in premenopausal
      patients. In conclusion, high vitamin D levels at early breast cancer diagnosis
      correlate with lower tumor size and better OS, and improve breast cancer-specific
      outcome, especially in postmenopausal patients.

PMID- 22623650
TI  - Chronic hepatitis C virus infection breaks tolerance and drives polyclonal
      expansion of autoreactive B cells.
AB  - Chronic Hepatitis C virus (HCV) infection has been linked with B cell
      lymphoproliferative disorders and several autoimmune-related diseases. The
      mechanisms of how chronic viral infection affects B cell development and
      predisposes the patients to autoimmune manifestations are poorly understood. In
      this study, we established an experimental system to probe the B cell responses
      and characterize the antibodies from chronic-HCV-infected individuals. We
      identified an unusual polyclonal expansion of the IgM memory B cell subset in
      some patients. This B cell subset is known to be tightly regulated, and
      autoreactive cells are eliminated by tolerance mechanisms. Genetic analysis of
      the immunoglobulin (Ig) heavy chain variable gene (V(H)) sequences of the
      expanded cell population showed that the levels of somatic hypermutation (SHM)
      correlate with the extent of cell expansion in the patients and that the V(H)
      genes exhibit signs of antigen-mediated selection. Functional analysis of the
      cloned B cell receptors demonstrated autoreactivity in some of the expanded IgM
      memory B cells in the patients which is not found in healthy donors. In summary,
      this study demonstrated that, in some patients, chronic HCV infection disrupts
      the tolerance mechanism that normally deletes autoreactive B cells, therefore
      increasing the risk of developing autoimmune antibodies. Long-term follow-up of
      this expanded B cell subset within the infected individuals will help determine
      whether these cells are predictors of more-serious clinical manifestations.

PMID- 22623649
TI  - Interplay between smoking-induced genotoxicity and altered signaling in
      pancreatic carcinogenesis.
AB  - Despite continuous research efforts directed at early diagnosis and treatment of
      pancreatic cancer (PC), the status of patients affected by this deadly malignancy
      remains dismal. Its notoriety with regard to lack of early diagnosis and
      resistance to the current chemotherapeutics is due to accumulating signaling
      abnormalities. Hoarding experimental and epidemiological evidences have
      established a direct correlation between cigarette smoking and PC risk. The
      cancer initiating/promoting nature of cigarette smoke can be attributed to its
      various constituents including nicotine, which is the major psychoactive
      component, and several other toxic constituents, such as nitrosamines, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone, and polycyclic aromatic
      hydrocarbons. These predominant smoke-constituents initiate a series of oncogenic
      events facilitating epigenetic alterations, self-sufficiency in growth signals,
      evasion of apoptosis, sustained angiogenesis, and metastasis. A better
      understanding of the molecular mechanisms underpinning these events is crucial
      for the prevention and therapeutic intervention against PC. This review presents
      various interconnected signal transduction cascades, the smoking-mediated
      genotoxicity, and genetic polymorphisms influencing the susceptibility for
      smoking-mediated PC development by modulating pivotal biological aspects such as
      cell defense/tumor suppression, inflammation, DNA repair, as well as tobacco
      carcinogen metabolization. Additionally, it provides a large perspective toward
      tumor biology and the therapeutic approaches against PC by targeting one or
      several steps of smoking-mediated signaling cascades.

PMID- 22623651
TI  - Lack of interference with immunogenicity of a chimeric alphavirus replicon
      particle-based influenza vaccine by preexisting antivector immunity.
AB  - Antivector immunity has been recognized as a potential caveat of using virus
      based vaccines. In the present study, an alphavirus-based replicon particle
      vaccine platform, which has demonstrated robust immunogenicity in animal models,
      was tested for effects of antivector immunity on immunogenicity against
      hemagglutinin of influenza virus as a target antigen and efficacy for protection
      against lethal challenge with the virus. Chimeric alphavirus-based replicon
      particles, comprising Venezuelan equine encephalitis virus nonstructural and
      Sindbis virus structural components, induced efficient protective antibody
      responses, which were not adversely influenced after multiple immunizations with
      the same vector expressing various antigens.

PMID- 22623652
TI  - The FomA porin from Fusobacterium nucleatum is a Toll-like receptor 2 agonist
      with immune adjuvant activity.
AB  - Many bacterial components selectively activate immune and nonhematopoietic target
      cells via Toll-like receptor (TLR) signaling; modulation of such host responses
      defines the immune adjuvant properties of these bacterial products. For example,
      the outer membrane protein porins from Neisseria, Salmonella, and Shigella are
      known TLR2 agonists with established systemic and mucosal immune adjuvanticity.
      Early work indicated that the FomA porin from Fusobacterium nucleatum has immune
      adjuvant activity in mice. Using a purified recombinant FomA, we have verified
      its immune stimulatory properties and have defined a role for TLR2 signaling in
      its in vitro and in vivo activity. FomA induces interleukin 8 (IL-8) secretion
      and NF-kappaB-dependent luciferase activity in HEK cells expressing TLR2, IL-6
      secretion, and cell surface upregulation of CD86 and major histocompatibility
      complex (MHC) II in primary B cells from wild-type mice, but it fails to activate
      cells from TLR2 knockout mice. Accordingly, the immune adjuvant activity of FomA
      is also TLR2 dependent. In a mouse model of immunization with ovalbumin (OVA),
      FomA induces enhanced production of OVA-specific IgM and IgG, including IgG1 and
      IgG2b antibodies, as well as enhanced secretion of IL-10 and IL-6, consistent
      with a Th2-type adjuvant effect. We also observe a moderate production of anti
      FomA antibodies, suggesting that FomA is also immunogenic, a quality that is also
      TLR2 dependent. Therefore, modulation of host immune responses by FomA may be
      effective for targeting general host immunity not only to pathogens (as a novel
      TLR2 adjuvant) but also to F. nucleatum itself (as an antigen), expanding its use
      as a self-adjuvanted antigen in an immunization strategy against polymicrobial
      infections, including those by F. nucleatum.

PMID- 22623653
TI  - Evaluation of commonly used serological tests for detection of Coxiella burnetii
      antibodies in well-defined acute and follow-up sera.
AB  - In this study, we compared Coxiella burnetii IgG phase I, IgG phase II, and IgM
      phase II detection among a commercially available enzyme-linked immunosorbent
      assay (ELISA) (Virion/Serion), an indirect fluorescent antibody test (IFAT)
      (Focus Diagnostics), and a complement fixation test (CFT) (Virion/Serion). For
      this, we used a unique collection of acute- and convalescent-phase sera from 126
      patients with acute Q fever diagnosed by positive Coxiella burnetii PCR of blood.
      We were able to establish a reliable date of onset of disease, since DNA is
      detectable within 2 weeks after the start of symptoms. In acute samples, at t =
      0, IFAT demonstrated IgM phase II antibodies in significantly more sera than did
      ELISA (31.8% versus 19.7%), although the portion of solitary IgM phase II was
      equal for IFAT and for ELISA (18.2% and 16.7%, respectively). Twelve months after
      the diagnosis of acute Q fever, 83.5% and 62.2% of the sera were still positive
      for IgM phase II with IFAT and ELISA, respectively. At 12 months IFAT IgG phase
      II showed the slowest decline. Therefore, definitive serological evidence of
      acute Q fever cannot be based on a single serum sample in areas of epidemicity
      and should involve measurement of both IgM and IgG antibodies in paired serum.
      Based on IgG phase II antibody detection in paired samples (at 0 and 3 months)
      from 62 patients, IFAT confirmed more cases than ELISA and CFT, but the
      differences were not statically significant (100% for IFAT, 95.2% for ELISA, and
      96.8% for CFT). This study demonstrated that the three serological tests are
      equally effective in diagnosing acute Q fever within 3 months of start of
      symptoms. In follow-up sera, more IgG antibodies were detected by IFAT than by
      ELISA or CFT, making IFAT more suitable for prevaccination screening programs.

PMID- 22623654
TI  - Microscale AMPAR reorganization and dynamics of the postsynaptic density.

PMID- 22623655
TI  - Correlated voltage dependences of ion channels revealed.

PMID- 22623656
TI  - Bimodal control of fear-coping strategies by CB1 cannabinoid receptors.
AB  - To maximize their chances of survival, animals need to rapidly and efficiently
      respond to aversive situations. These responses can be classified as active or
      passive and depend on the specific nature of threats, but also on individual fear
      coping styles. In this study, we show that the control of excitatory and
      inhibitory brain neurons by type-1 cannabinoid (CB1) receptors is a key
      determinant of fear coping strategies in mice. In classical fear conditioning, a
      switch between initially predominant passive fear responses (freezing) and active
      behaviors (escape attempts and risk assessment) develops over time. Constitutive
      genetic deletion of CB1 receptors in CB1-/- mice disrupted this pattern by
      favoring passive responses. This phenotype can be ascribed to endocannabinoid
      control of excitatory neurons, because it was reproduced in conditional mutant
      mice lacking CB1 receptors from cortical glutamatergic neurons. CB1 receptor
      deletion from GABAergic brain neurons led to the opposite phenotype,
      characterized by the predominance of active coping. The CB1 receptor agonist
      Delta9-tetrahydrocannabinol exerted a biphasic control of fear coping strategies,
      with lower and higher doses favoring active and passive responses, respectively.
      Finally, viral re-expression of CB1 receptors in the amygdala of CB1-/- mice
      restored the normal switch between the two coping strategies. These data strongly
      suggest that CB1 receptor signaling bimodally controls the spontaneous adoption
      of active or passive coping strategies in individuals. This primary function of
      the endocannabinoid system in shaping individual behavioral traits should be
      considered when studying the mechanisms of physiological and pathological fear.

PMID- 22623657
TI  - Palmitoylation of A-kinase anchoring protein 79/150 regulates dendritic endosomal
      targeting and synaptic plasticity mechanisms.
AB  - NMDA receptor-dependent long-term potentiation (LTP) and depression (LTD) are
      forms of synaptic plasticity underlying learning and memory that are expressed
      through increases and decreases, respectively, in dendritic spine size and AMPA
      receptor (AMPAR) phosphorylation and postsynaptic localization. The A-kinase
      anchoring protein 79/150 (AKAP79/150) signaling scaffold regulates AMPAR
      phosphorylation, channel activity, and endosomal trafficking associated with LTP
      and LTD. AKAP79/150 is targeted to dendritic spine plasma membranes by an N
      terminal polybasic domain that binds phosphoinositide lipids, F-actin, and
      cadherin cell adhesion molecules. However, we do not understand how regulation of
      AKAP targeting controls AMPAR endosomal trafficking. Here, we report that
      palmitoylation of the AKAP N-terminal polybasic domain targets it to postsynaptic
      lipid rafts and dendritic recycling endosomes. AKAP palmitoylation was regulated
      by seizure activity in vivo and LTP/LTD plasticity-inducing stimuli in cultured
      rat hippocampal neurons. With chemical LTP induction, we observed AKAP79
      dendritic spine recruitment that required palmityolation and Rab11-regulated
      endosome recycling coincident with spine enlargement and AMPAR surface delivery.
      Importantly, a palmitoylation-deficient AKAP79 mutant impaired regulation of
      spine size, endosome recycling, AMPAR trafficking, and synaptic potentiation.
      These findings emphasize the emerging importance of palmitoylation in controlling
      synaptic function and reveal novel roles for the AKAP79/150 signaling complex in
      dendritic endosomes.

PMID- 22623658
TI  - Hyperdynamic microtubules, cognitive deficits, and pathology are improved in tau
      transgenic mice with low doses of the microtubule-stabilizing agent BMS-241027.
AB  - Tau is a microtubule (MT)-stabilizing protein that is altered in Alzheimer's
      disease (AD) and other tauopathies. It is hypothesized that the
      hyperphosphorylated, conformationally altered, and multimeric forms of tau lead
      to a disruption of MT stability; however, direct evidence is lacking in vivo. In
      this study, an in vivo stable isotope-mass spectrometric technique was used to
      measure the turnover, or dynamicity, of MTs in brains of living animals. We
      demonstrated an age-dependent increase in MT dynamics in two different tau
      transgenic mouse models, 3xTg and rTg4510. MT hyperdynamicity was dependent on
      tau expression, since a reduction of transgene expression with doxycycline
      reversed the MT changes. Treatment of rTg4510 mice with the epothilone, BMS
      241027, also restored MT dynamics to baseline levels. In addition, MT
      stabilization with BMS-241027 had beneficial effects on Morris water maze
      deficits, tau pathology, and neurodegeneration. Interestingly, pathological and
      functional benefits of BMS-241027 were observed at doses that only partially
      reversed MT hyperdynamicity. Together, these data suggest that tau-mediated loss
      of MT stability may contribute to disease progression and that very low doses of
      BMS-241027 may be useful in the treatment of AD and other tauopathies.

PMID- 22623659
TI  - Your goal is mine: unraveling mimetic desires in the human brain.
AB  - The spread of desires among individuals is widely believed to shape motivational
      drives in human populations. However, objective evidence for this phenomenon and
      insights into the underlying brain mechanisms are still lacking. Here we show
      that participants rated objects as more desirable once perceived as the goals of
      another agent's action. We then unravel the mechanisms underpinning such goal
      contagion, using functional neuroimaging. As expected, observing goal-directed
      actions activated a parietofrontal network known as the mirror neuron system
      (MNS), whereas subjective desirability ratings were represented in a ventral
      striatoprefrontal network known as the brain valuation system (BVS). Crucially,
      the induction of mimetic desires through action observation involved the
      modulation of BVS activity through MNS activity. Furthermore, MNS-BVS effective
      connectivity predicted individual susceptibility toward mimetic desires. We
      therefore suggest that MNS-BVS interaction represents a fundamental mechanism
      explaining how nonverbal behavior propagates desires without the need for
      explicit, intentional communication.

PMID- 22623661
TI  - Neural measures reveal a fixed item limit in subitizing.
AB  - For centuries, it has been known that humans can rapidly and accurately enumerate
      small sets of items, a process referred to as subitizing. However, there is still
      active debate regarding the mechanisms that mediate this ability. For example,
      some have argued that subitizing reflects the operation of a fixed-capacity
      individuation mechanism that enables concurrent access to a small number of
      items. However, others have argued that subitizing reflects the operation of a
      continuous numerical estimation mechanism whose precision varies with numerosity
      in a manner consistent with Weber's law. Critically, quantitative models based on
      either of these predictions can provide a reasonable description of subitizing
      performance, making it difficult to discriminate between these alternatives
      solely on the basis of subjects' behavioral performance. Here, we attempted to
      discriminate between fixed-capacity and continuous estimation models of
      subitizing using neural measures. In two experiments, we recorded EEGs while
      subjects performed a demanding subitizing task and examined set-size-dependent
      changes in a neurophysiological marker of visual selection (the N2pc event
      related potential component) evoked by an array of to-be-enumerated items. In
      both experiments, N2pc amplitudes increased monotonically within the subitizing
      range before reaching an asymptotic limit at approximately three items. Moreover,
      inter-participant differences in the location of this asymptote were strongly
      predictive of behavioral estimates of subitizing span derived from a fixed
      capacity model. Thus, neural activity linked with subitizing ability shows
      evidence of an early and discrete limit in the number of items that can be
      concurrently apprehended, supporting a fixed-capacity model of this process.

PMID- 22623660
TI  - p38 MAPK activation promotes denervated Schwann cell phenotype and functions as a
      negative regulator of Schwann cell differentiation and myelination.
AB  - Physical damage to the peripheral nerves triggers Schwann cell injury response in
      the distal nerves in an event termed Wallerian degeneration: the Schwann cells
      degrade their myelin sheaths and dedifferentiate, reverting to a phenotype that
      supports axon regeneration and nerve repair. The molecular mechanisms regulating
      Schwann cell plasticity in the PNS remain to be elucidated. Using both in vivo
      and in vitro models for peripheral nerve injury, here we show that inhibition of
      p38 mitogen-activated protein kinase (MAPK) activity in mice blocks Schwann cell
      demyelination and dedifferentiation following nerve injury, suggesting that the
      kinase mediates the injury signal that triggers distal Schwann cell injury
      response. In myelinating cocultures, p38 MAPK also mediates myelin breakdown
      induced by Schwann cell growth factors, such as neuregulin and FGF-2.
      Furthermore, ectopic activation of p38 MAPK is sufficient to induce myelin
      breakdown and drives differentiated Schwann cells to acquire phenotypic features
      of immature Schwann cells. We also show that p38 MAPK concomitantly functions as
      a negative regulator of Schwann cell differentiation: enforced p38 MAPK
      activation blocks cAMP-induced expression of Krox 20 and myelin proteins, but
      induces expression of c-Jun. As expected of its role as a negative signal for
      myelination, inhibition of p38 MAPK in cocultures promotes myelin formation by
      increasing the number as well as the length of individual myelin segments.
      Altogether, our data identify p38 MAPK as an important regulator of Schwann cell
      plasticity and differentiation.

PMID- 22623662
TI  - Identification of two functionally distinct endosomal recycling pathways for
      dopamine D2 receptor.
AB  - Dopamine D2 receptor (DRD2) is important for normal function of the brain reward
      circuit. Lower DRD2 function in the brain increases the risk for substance abuse,
      obesity, attention deficit/hyperactivity disorder, and depression. Moreover, DRD2
      is the target of most antipsychotics currently in use. It is well known that
      dopamine-induced DRD2 endocytosis is important for its desensitization. However,
      it remains controversial whether DRD2 is recycled back to the plasma membrane or
      targeted for degradation following dopamine stimulation. Here, we used total
      internal reflection fluorescent microscopy (TIRFM) to image DRD2 with a
      superecliptic pHluorin tagged to its N terminus. With these technical advances,
      we were able to directly visualize vesicular insertion events of DRD2 in cultured
      mouse striatal medium spiny neurons. We showed that insertion of DRD2 occurs on
      neuronal somatic and dendritic surfaces. Lateral diffusion of DRD2 was observed
      following its insertion. Most importantly, using our new approach, we uncovered
      two functionally distinct recycling pathways for DRD2: a constitutive recycling
      pathway and a dopamine activity-dependent recycling pathway. We further
      demonstrated that Rab4 plays an important role in constitutive DRD2 recycling,
      while Rab11 is required for dopamine activity-dependent DRD2 recycling. Finally,
      we demonstrated that the two DRD2 recycling pathways play distinct roles in
      determining DRD2 function: the Rab4-sensitive constitutive DRD2 recycling pathway
      determines steady-state surface expression levels of DRD2, whereas the Rab11
      sensitive dopamine activity-dependent DRD2 recycling pathway is important for
      functional resensitization of DRD2. Our findings underscore the significance of
      endosomal recycling in regulation of DRD2 function.

PMID- 22623663
TI  - Fibroblast growth factor 8 organizes the neocortical area map and regulates
      sensory map topography.
AB  - The concept of an "organizer" is basic to embryology. An organizer is a portion
      of the embryo producing signals that lead to the creation of a patterned mature
      structure from an embryonic primordium. Fibroblast growth factor 8 (FGF8) is a
      morphogen that disperses from a rostromedial source in the neocortical primordium
      (NP), forms a rostral-to-caudal (R/C) gradient, and regulates embryonic and
      neonatal R/C patterns of gene expression in neocortex. Whether FGF8 also has
      organizer activity that generates the postnatal neocortical area map is
      uncertain. To test this possibility, new sources of FGF8 were introduced into the
      mouse NP with in utero microelectroporation at embryonic day 10.5, close to the
      estimated peak of area patterning. Results differed depending on the position of
      ectopic FGF8. Ectopic FGF8 in the caudalmost NP could duplicate somatosensory
      cortex (S1) and primary visual cortex (V1). FGF8 delivered to the midlateral NP
      generated a sulcus separating rostral and caudal portions of the NP, in effect
      creating duplicate NPs. In the caudal NP, ectopic FGF8 induced a second,
      inclusive area map, containing frontal cortex, S1, V1, and primary auditory
      areas. Moreover, duplicate S1 showed plasticity to sensory deprivation, and
      duplicate V1 responded to visual stimuli. Our findings implicate FGF8 as an
      organizer signal, and its source in the rostromedial telencephalon as an
      organizer of the neocortical area map.

PMID- 22623664
TI  - Scene representations in parahippocampal cortex depend on temporal context.
AB  - Human perception is supported by regions of ventral visual cortex that become
      active when specific types of information appear in the environment. This
      coupling has led to a common assumption in cognitive neuroscience that stimulus
      evoked activity in these regions only reflects information about the current
      stimulus. Here we challenge this assumption for how scenes are represented in a
      scene-selective region of parahippocampal cortex. This region treated two
      identical scenes as more similar when they were preceded in time by the same
      stimuli compared to when they were preceded by different stimuli. These findings
      suggest that parahippocampal cortex embeds scenes in their temporal context to
      determine what they represent. By integrating the past and present, such
      representations may support the encoding and navigation of complex environments.

PMID- 22623665
TI  - Retinal guanylyl cyclase isozyme 1 is the preferential in vivo target for
      constitutively active GCAP1 mutants causing congenital degeneration of
      photoreceptors.
AB  - Two calcium-sensitive guanylyl cyclase activating proteins (GCAP1 and GCAP2)
      activate cGMP synthesis in photoreceptor by retinal membrane guanylyl cyclase
      isozymes (RetGC1 and RetGC2) to expedite recovery, but calcium-insensitive
      constitutively active GCAP1 mutants cause photoreceptor degeneration in human
      patients and transgenic mice. Although GCAP1 and GCAP2 can both activate RetGC1
      and RetGC2 in vitro, we find that GCAP1 selectively regulates RetGC1 in vivo.
      Furthermore, elimination of RetGC1 but not RetGC2 isozyme reverses abnormal
      calcium sensitivity of cGMP synthesis and rescues mouse rods in transgenic mice
      expressing GCAP1 mutants causing photoreceptor disease. Rods expressing mutant
      GCAP1 not only survive in the absence of RetGC1 but also remain functional,
      albeit with reduced electroretinography (ERG) amplitudes typical of RetGC1-/-
      genotype. The rod ERG recovery from a strong flash, only slightly affected in
      both RetGC1-/- and RetGC2-/- mice, becomes very slow in RetGC1-/- but not RetGC2
      /- mice when GCAP2 is not available to provide Ca2+ feedback to the remaining
      RetGC isozyme. The intrinsic biochemical properties of RetGC and GCAP determined
      in vitro do not explain the observed phenomena. Instead, our results argue that
      there must be a cellular mechanism that limits GCAP1 access to RetGC2 and makes
      RetGC1 isozyme a preferential target for the disease-causing GCAP1 mutants. A
      more general conclusion from our findings is that nondiscriminatory interactions
      between homologous effector enzymes and their regulatory proteins permitted by
      their intrinsic biochemical properties can be effectively restricted in a living
      photoreceptor.

PMID- 22623666
TI  - From animal model to human brain networking: dynamic causal modeling of
      motivational systems.
AB  - An organism's behavior is sensitive to different reinforcements in the
      environment. Based on extensive animal literature, the reinforcement sensitivity
      theory (RST) proposes three separate neurobehavioral systems to account for such
      context-sensitive behavior, affecting the tendency to react to punishment,
      reward, or goal-conflict stimuli. The translation of animal findings to complex
      human behavior, however, is far from obvious. To examine whether the neural
      networks underlying humans' motivational processes are similar to those proposed
      by the RST model, we conducted a functional MRI study, in which 24 healthy
      subjects performed an interactive game that engaged the different motivational
      systems using distinct time periods (states) of punishment, reward, and conflict.
      Crucially, we found that the different motivational states elicited activations
      in brain regions that corresponded exactly to the brain systems underlying RST.
      Moreover, dynamic causal modeling of each motivational system confirmed that the
      coupling strengths between the key brain regions of each system were enabled
      selectively by the appropriate motivational state. These results may shed light
      on the impairments that underlie psychopathologies associated with dysfunctional
      motivational processes and provide a translational validity for the RST.

PMID- 22623667
TI  - Plasticity of recurrent inhibition in the Drosophila antennal lobe.
AB  - Recurrent inhibition, wherein excitatory principal neurons stimulate inhibitory
      interneurons that feedback on the same principal cells, occurs ubiquitously in
      the brain. However, the regulation and function of recurrent inhibition are
      poorly understood in terms of the contributing interneuron subtypes as well as
      their effect on neural and cognitive outputs. In the Drosophila olfactory system,
      odorants activate olfactory sensory neurons (OSNs), which stimulate projection
      neurons (PNs) in the antennal lobe. Both OSNs and PNs activate local inhibitory
      neurons (LNs) that provide either feedforward or recurrent/feedback inhibition in
      the lobe. During olfactory habituation, prior exposure to an odorant selectively
      decreases the animal's subsequent response to the odorant. We show here that
      habituation occurs in response to feedback from PNs. Output from PNs is necessary
      for olfactory habituation and, in the absence of odorant, direct PN activation is
      sufficient to induce the odorant-selective behavioral attenuation characteristic
      of olfactory habituation. PN-induced habituation occludes further odor-induced
      habituation and similarly requires GABA(A)Rs and NMDARs in PNs, as well as VGLUT
      and cAMP signaling in the multiglomerular inhibitory local interneurons (LN1)
      type of LN. Thus, PN output is monitored by an LN subtype whose resultant
      plasticity underlies behavioral habituation. We propose that recurrent inhibitory
      motifs common in neural circuits may similarly underlie habituation to other
      complex stimuli.

PMID- 22623669
TI  - Uncovering a context-specific connectional fingerprint of human dorsal premotor
      cortex.
AB  - Primate electrophysiological and lesion studies indicate a prominent role of the
      left dorsal premotor cortex (PMd) in action selection based on learned
      sensorimotor associations. Here we applied transcranial magnetic stimulation
      (TMS) to human left PMd at low or high intensity while right-handed individuals
      performed externally paced sequential key presses with their left hand. Movements
      were cued by abstract visual stimuli, and subjects either freely selected a key
      press or responded according to a prelearned visuomotor mapping rule. Continuous
      arterial spin labeling was interleaved with TMS to directly assess how
      stimulation of left PMd modulates task-related brain activity depending on the
      mode of movement selection. Relative to passive viewing, both tasks activated a
      frontoparietal motor network. Compared with low-intensity TMS, high-intensity TMS
      of left PMd was associated with an increase in activity in medial and right
      premotor areas without affecting task performance. Critically, this increase in
      task-related activity was only present when movement selection relied on
      arbitrary visuomotor associations but not during freely selected movements.
      Psychophysiological interaction analysis revealed a context-specific increase in
      functional coupling between the stimulated left PMd and remote right-hemispheric
      and mesial motor regions that was only present during arbitrary visuomotor
      mapping. Our TMS perturbation approach yielded causal evidence that the left PMd
      is implicated in mapping external cues onto the appropriate movement in humans.
      Furthermore, the data suggest that the left PMd may transiently form a functional
      network together with right-hemispheric and mesial motor regions to sustain
      visuomotor mapping performed with the left nondominant hand.

PMID- 22623668
TI  - An ankyrinG-binding motif is necessary and sufficient for targeting Nav1.6 sodium
      channels to axon initial segments and nodes of Ranvier.
AB  - Neurons are highly polarized cells with functionally distinct axonal and
      somatodendritic compartments. Voltage-gated sodium channels Na(v)1.2 and Na(v)1.6
      are highly enriched at axon initial segments (AISs) and nodes of Ranvier, where
      they are necessary for generation and propagation of action potentials. Previous
      studies using reporter proteins in unmyelinated cultured neurons suggest that an
      ankyrinG-binding motif within intracellular loop 2 (L2) of sodium channels is
      sufficient for targeting these channels to the AIS, but mechanisms of channel
      targeting to nodes remain poorly understood. Using a CD4-Na(v)1.2/L2 reporter
      protein in rat dorsal root ganglion neuron-Schwann cell myelinating cocultures,
      we show that the ankyrinG-binding motif is sufficient for protein targeting to
      nodes of Ranvier. However, reporter proteins cannot capture the complexity of
      full-length channels. To determine how native, full-length sodium channels are
      clustered in axons, and to show the feasibility of studying these channels in
      vivo, we constructed fluorescently tagged and functional mouse Na(v)1.6 channels
      for in vivo analysis using in utero brain electroporation. We show here that wild
      type tagged-Na(v)1.6 channels are efficiently clustered at nodes and AISs in
      vivo. Furthermore, we show that mutation of a single invariant glutamic acid
      residue (E1100) within the ankyrinG-binding motif blocked Na(v)1.6 targeting in
      neurons both in vitro and in vivo. Additionally, we show that caseine kinase
      phosphorylation sites within this motif, while not essential for targeting, can
      modulate clustering at the AIS. Thus, the ankyrinG-binding motif is both
      necessary and sufficient for the clustering of sodium channels at nodes of
      Ranvier and the AIS.

PMID- 22623670
TI  - Recollection and familiarity make independent contributions to memory judgments.
AB  - Recognition memory can be supported by the processes of recollection and
      familiarity. Recollection is recovery of qualitative information about a prior
      event. Familiarity is a scalar strength signal that permits judgments of prior
      occurrence. There is vigorous debate about how these processes are
      conceptualized, how they contribute to memory judgments, and which brain regions
      support them. One popular method for investigating these questions is the
      Remember/Know procedure, where subjects give a Remember response to studied
      stimuli for which they can recover contextual details of the study encounter, and
      a Know response when details are not recovered but subjects nevertheless believe
      that a stimulus was studied. According to one model, Remember responses are
      strong memories that are typically associated with relatively high levels of
      recollection and familiarity. Know responses are weaker memories and are
      typically associated with lower levels of both processes. Data inconsistent with
      this account were obtained in this experiment, where magnetoencephalographic
      (MEG) measures of neural activity were acquired in the test phase of a verbal
      memory task where healthy human volunteers made Remember, Know, or New judgments
      to studied and unstudied words. An MEG index of the process of recollection was
      larger for Remember than Know judgments, whereas the reverse was true for a MEG
      index of familiarity. Critically, this result is predicted by a model where
      recollection and familiarity make independent contributions to Remember and Know
      judgments, and provides a powerful constraint when mapping memory processes onto
      their neural substrates.

PMID- 22623671
TI  - Initial neighborhood biases and the quality of motion stimulation jointly
      influence the rapid emergence of direction preference in visual cortex.
AB  - Visual experience plays a critical role in the development of direction-selective
      responses in ferret visual cortex. In visually naive animals, presentation of a
      bidirectional "training" stimulus induces rapid increases in the direction
      selective responses of single neurons that can be predicted by small but
      significant direction biases that are present in neighboring neurons at the onset
      of stimulation. In this study we used in vivo two-photon imaging of calcium
      signals to further explore the contribution of visual experience to the emergence
      of direction- selective responses in ferret visual cortex. The first set of
      experiments was designed to determine whether visual experience is required for
      the development of the initial neighborhood bias. In animals that were dark
      reared until the time of eye opening, we found that individual neurons exhibited
      weak direction-selective responses accompanied by a reduced but statistically
      significant neighborhood bias, indicating that both features arise without the
      need for visual experience. The second set of experiments used a unidirectional
      training stimulus to assess the relative roles of the neighborhood bias and
      visual experience in determining the direction preference that cortical neurons
      acquire during direction training. We found that neurons became more responsive
      to the trained direction even when they were located in regions of the cortex
      with an initial neighborhood bias for the direction opposite the training
      stimulus. Together, these results suggest an adaptive developmental strategy for
      the elaboration of direction-selective responses, one in which experience
      independent mechanisms provide a symmetry-breaking seed for the instructive
      effects of visual experience.

PMID- 22623672
TI  - Activity-dependent alternative splicing increases persistent sodium current and
      promotes seizure.
AB  - Activity of voltage-gated Na channels (Na(v)) is modified by alternative
      splicing. However, whether altered splicing of human Na(v)s contributes to
      epilepsy remains to be conclusively shown. We show here that altered splicing of
      the Drosophila Na(v) (paralytic, DmNa(v)) contributes to seizure-like behavior in
      identified seizure mutants. We focus attention on a pair of mutually exclusive
      alternate exons (termed K and L), which form part of the voltage sensor (S4) in
      domain III of the expressed channel. The presence of exon L results in a large,
      non-inactivating, persistent I(Nap). Many forms of human epilepsy are associated
      with an increase in this current. In wild-type (WT) Drosophila larvae, ~70-80% of
      DmNa(v) transcripts contain exon L, and the remainder contain exon K. Splicing of
      DmNa(v) to include exon L is increased to ~100% in both the slamdance and easily
      shocked seizure mutants. This change to splicing is prevented by reducing
      synaptic activity levels through exposure to the antiepileptic phenytoin or the
      inhibitory transmitter GABA. Conversely, enhancing synaptic activity in WT, by
      feeding of picrotoxin is sufficient to increase I(Nap) and promote seizure
      through increased inclusion of exon L to 100%. We also show that the underlying
      activity-dependent mechanism requires the presence of Pasilla, an RNA-binding
      protein. Finally, we use computational modeling to show that increasing I(Nap) is
      sufficient to potentiate membrane excitability consistent with a seizure
      phenotype. Thus, increased synaptic excitation favors inclusion of exon L, which,
      in turn, further increases neuronal excitability. Thus, at least in Drosophila,
      this self-reinforcing cycle may promote the incidence of seizure.

PMID- 22623673
TI  - Lymphocyte cell kinase activation mediates neuroprotection during ischemic
      preconditioning.
AB  - The molecular mechanisms underlying preconditioning (PC), a powerful endogenous
      neuroprotective phenomenon, remain to be fully elucidated. Once identified, these
      endogenous mechanisms could be manipulated for therapeutic gain. We investigated
      whether lymphocyte cell kinase (Lck), a member of the Src kinases family,
      mediates PC. We used both in vitro primary cortical neurons and in vivo mouse
      cerebral focal ischemia models of preconditioning, cellular injury, and
      neuroprotection. Genetically engineered mice deficient in Lck, gene silencing
      using siRNA, and pharmacological approaches were used. Cortical neurons
      preconditioned with sublethal exposure to NMDA or oxygen glucose deprivation
      (OGD) exhibited enhanced Lck kinase activity, and were resistant to injury on
      subsequent exposure to lethal levels of NMDA or OGD. Lck gene silencing using
      siRNA abolished tolerance against both stimuli. Lck-/- mice or neurons isolated
      from Lck-/- mice did not exhibit PC-induced tolerance. An Lck antagonist
      administered to wild-type mice significantly attenuated the neuroprotective
      effect of PC in the mouse focal ischemia model. Using pharmacological and gene
      silencing strategies, we also showed that PKCepsilon is an upstream regulator of
      Lck, and Fyn is a downstream target of Lck. We have discovered that Lck plays an
      essential role in PC in both cellular and animal models of stroke. Our data also
      show that the PKCepsilon-Lck-Fyn axis is a key mediator of PC. These findings
      provide new opportunities for stroke therapy development.

PMID- 22623674
TI  - Integration of H-2Z1, a somatosensory cortex-expressed transgene, interferes with
      the expression of the Satb1 and Tbc1d5 flanking genes and affects the
      differentiation of a subset of cortical interneurons.
AB  - H-2Z1 is an enhancer trap transgenic mouse line in which the lacZ reporter
      delineates the somatosensory area of the cerebral cortex where it is expressed in
      a subset of layer IV neurons. In the search of somatosensory specific genes or
      regulatory sequences, we mapped the H-2Z1 transgene insertion site to chromosome
      17, 100 and 460 kb away from Tbc1d5 and Satb1 flanking genes. We show here that
      insertion of the H-2Z1 transgene results in three distinct outcomes. First, a
      genetic background-sensitive expression of lacZ in several brain and body
      structures. While four genes in a 1 Mb region around the insertion are expressed
      in the barrel cortex, H-2Z1 expression resembles more that of its two direct
      neighbors. Moreover, H-2Z1 closely reports most of the body and brain expression
      sites of the Satb1 chromatin remodeling gene including tooth buds, thymic
      epithelium, pontine nuclei, fastigial cerebellar nuclei, and cerebral cortex.
      Second, the H-2Z1 transgene causes insertional mutagenesis of Tbc1d5 and Satb1,
      leading to a strong decrease in their expressions. Finally, insertion of H-2Z1
      affects the differentiation of a subset of cortical GABAergic interneurons, a
      possible consequence of downregulation of Satb1 expression. Thus, the H-2Z1
      "somatosensory" transgene is inserted in the regulatory landscape of two genes
      highly expressed in the developing somatosensory cortex and reports for a
      subdomain of their expression profiles. Together, our data suggest that
      regulation of H-2Z1 expression results from local and remote genetic
      interactions.

PMID- 22623675
TI  - In vivo visualization of delta opioid receptors upon physiological activation
      uncovers a distinct internalization profile.
AB  - G-protein-coupled receptors (GPCRs) mediate numerous physiological functions and
      represent prime therapeutic targets. Receptor trafficking upon agonist
      stimulation is critical for GPCR function, but examining this process in vivo
      remains a true challenge. Using knock-in mice expressing functional fluorescent
      delta opioid receptors under the control of the endogenous promoter, we
      visualized in vivo internalization of this native GPCR upon physiological
      stimulation. We developed a paradigm in which animals were made dependent on
      morphine in a drug-paired context. When re-exposed to this context in a drug-free
      state, mice showed context-dependent withdrawal signs and activation of the
      hippocampus. Receptor internalization was transiently detected in a subset of CA1
      neurons, uncovering regionally restricted opioid peptide release. Importantly, a
      pool of surface receptors always remained, which contrasts with the in vivo
      profile previously established for exogenous drug-induced internalization.
      Therefore, a distinct response is observed at the receptor level upon a
      physiological or pharmacological stimulation. Altogether, direct in vivo GPCR
      visualization enables mapping receptor stimulation promoted by a behavioral
      challenge and represents a powerful approach to study endogenous GPCR physiology.

PMID- 22623676
TI  - Single-neuron responses in the human nucleus accumbens during a financial
      decision-making task.
AB  - Linking values to actions and evaluating expectations relative to outcomes are
      both central to reinforcement learning and are thought to underlie financial
      decision-making. However, neurophysiology studies of these processes in humans
      remain limited. Here, we recorded the activity of single human nucleus accumbens
      neurons while subjects performed a gambling task. We show that the nucleus
      accumbens encodes two signals related to subject behavior. First, we find that
      under relatively predictable conditions, single neuronal activity predicts future
      financial decisions on a trial-by-trial basis. Interestingly, we show that this
      activity continues to predict decisions even under conditions of uncertainty
      (e.g., when the probability of winning or losing is 50/50 and no particular
      financial choice predicts a rewarding outcome). Furthermore, we find that this
      activity occurs, on average, 2 s before the subjects physically manifest their
      decision. Second, we find that the nucleus accumbens encodes the difference
      between expected and realized outcomes, consistent with a prediction error
      signal. We show this activity occurs immediately after the subject has realized
      the outcome of the trial and is present on both the individual and population
      neuron levels. These results provide human single neuronal evidence that the
      nucleus accumbens is integral in making financial decisions.

PMID- 22623677
TI  - Striatal dopamine D2/D3 receptors mediate response inhibition and related
      activity in frontostriatal neural circuitry in humans.
AB  - Impulsive behavior is thought to reflect a traitlike characteristic that can have
      broad consequences for an individual's success and well-being, but its
      neurobiological basis remains elusive. Although striatal dopamine D2-like
      receptors have been linked with impulsive behavior and behavioral inhibition in
      rodents, a role for D2-like receptor function in frontostriatal circuits
      mediating inhibitory control in humans has not been shown. We investigated this
      role in a study of healthy research participants who underwent positron emission
      tomography with the D2/D3 dopamine receptor ligand [18F]fallypride and BOLD fMRI
      while they performed the Stop-signal Task, a test of response inhibition.
      Striatal dopamine D2/D3 receptor availability was negatively correlated with
      speed of response inhibition (stop-signal reaction time) and positively
      correlated with inhibition-related fMRI activation in frontostriatal neural
      circuitry. Correlations involving D2/D3 receptor availability were strongest in
      the dorsal regions (caudate and putamen) of the striatum, consistent with
      findings of animal studies relating dopamine receptors and response inhibition.
      The results suggest that striatal D2-like receptor function in humans plays a
      major role in the neural circuitry that mediates behavioral control, an ability
      that is essential for adaptive responding and is compromised in a variety of
      common neuropsychiatric disorders.

PMID- 22623678
TI  - Kindlin-1 enhances axon growth on inhibitory chondroitin sulfate proteoglycans
      and promotes sensory axon regeneration.
AB  - Growing and regenerating axons need to interact with the molecules in the
      extracellular matrix as they traverse through their environment. An important
      group of receptors that serve this function is the integrin superfamily of cell
      surface receptors, which are evolutionarily conserved alphabeta heterodimeric
      transmembrane proteins. The function of integrins is controlled by regulating the
      affinity for ligands (also called "integrin activation"). Previous results have
      shown that CNS inhibitory molecules inactivate axonal integrins, while enhancing
      integrin activation can promote axon growth from neurons cultured on inhibitory
      substrates. We tested two related molecules, kindlin-1 and kindlin-2 (Fermitin
      family members 1 and 2), that can activate beta1, beta2, and beta3 integrins, for
      their effects on integrin signaling and integrin-mediated axon growth in rat
      sensory neurons. We determined that kindlin-2, but not kindlin-1, is endogenously
      expressed in the nervous system. Knocking down kindlin-2 levels in cultured
      sensory neurons impaired their ability to extend axons, but this was partially
      rescued by kindlin-1 expression. Overexpression of kindlin-1, but not kindlin-2,
      in cultured neurons increased axon growth on an inhibitory aggrecan substrate.
      This was found to be associated with enhanced integrin activation and signaling
      within the axons. Additionally, in an in vivo rat dorsal root injury model,
      transduction of dorsal root ganglion neurons to express kindlin-1 promoted axon
      regeneration across the dorsal root entry zone and into the spinal cord. These
      animals demonstrated improved recovery of thermal sensation following injury. Our
      results therefore suggest that kindlin-1 is a potential tool for improving axon
      regeneration after nervous system lesions.

PMID- 22623679
TI  - Synaptic distributions of GluA2 and PKMzeta in the monkey dentate gyrus and their
      relationships with aging and memory.
AB  - Rhesus monkeys provide a valuable model for studying the neurobiological basis of
      cognitive aging, because they are vulnerable to age-related memory decline in a
      manner similar to humans. In this study, young and aged monkeys were first tested
      on a well characterized recognition memory test (delayed nonmatching-to-sample;
      DNMS). Then, electron microscopic immunocytochemistry was performed to determine
      the subcellular localization of two proteins in the hippocampal dentate gyrus
      (DG): the GluA2 subunit of the glutamate AMPA receptor and the atypical protein
      kinase C zeta isoform (PKMzeta). PKMzeta promotes memory storage by regulating
      GluA2-containing AMPA receptor trafficking. Thus, we examined whether the
      distribution of GluA2 and PKMzeta is altered with aging in DG axospinous synapses
      and whether it is coupled with memory deficits. Monkeys with faster DNMS task
      acquisition and more accurate recognition memory exhibited higher proportions of
      dendritic spines coexpressing GluA2 and PKMzeta. These double-labeled spines had
      larger synapses, as measured by postsynaptic density area, than single-labeled
      and unlabeled spines. Within this population of double-labeled spines, aged
      monkeys compared with young expressed a lower density of synaptic GluA2
      immunogold labeling, which correlated with lower recognition accuracy.
      Additionally, higher density of synaptic PKMzeta labeling in double-labeled
      spines correlated with both faster task acquisition and better retention.
      Together, these findings suggest that age-related impairment in maintenance of
      GluA2 at the synapse in the primate hippocampus is coupled with memory deficits.

PMID- 22623680
TI  - A new mechanism for transmissible prion diseases.
AB  - The transmissible agent of prion disease consists of prion protein (PrP) in beta
      sheet-rich state (PrP(Sc)) that can replicate its conformation according to a
      template-assisted mechanism. This mechanism postulates that the folding pattern
      of a newly recruited polypeptide accurately reproduces that of the PrP(Sc)
      template. Here, three conformationally distinct amyloid states were prepared in
      vitro using Syrian hamster recombinant PrP (rPrP) in the absence of cellular
      cofactors. Surprisingly, no signs of prion infection were found in Syrian
      hamsters inoculated with rPrP fibrils that resembled PrP(Sc), whereas an
      alternative amyloid state, with a folding pattern different from that of PrP(Sc),
      induced a pathogenic process that led to transmissible prion disease. An atypical
      proteinase K-resistant, transmissible PrP form that resembled the structure of
      the amyloid seeds was observed during a clinically silent stage before authentic
      PrP(Sc) emerged. The dynamics between the two forms suggest that atypical
      proteinase K-resistant PrP (PrPres) gave rise to PrP(Sc). While no PrP(Sc) was
      found in preparations of fibrils using protein misfolding cyclic amplification
      with beads (PMCAb), rPrP fibrils gave rise to atypical PrPres in modified PMCAb,
      suggesting that atypical PrPres was the first product of PrP(C) misfolding
      triggered by fibrils. The current work demonstrates that a new mechanism
      responsible for prion diseases different from the PrP(Sc)-templated or
      spontaneous conversion of PrP(C) into PrP(Sc) exists. This study provides
      compelling evidence that noninfectious amyloids with a structure different from
      that of PrP(Sc) could lead to transmissible prion disease. This work has numerous
      implications for understanding the etiology of prion and other neurodegenerative
      diseases.

PMID- 22623681
TI  - Acetylcholine receptors enable the transport of rapsyn from the Golgi complex to
      the plasma membrane.
AB  - The accumulation of acetylcholine receptors (AChRs) at nerve terminals is
      critical for signal transmission at the neuromuscular junction, and rapsyn is
      essential for this process. Previous studies suggest that AChRs might direct
      rapsyn self-clusters to the synapse. In vivo experiments with fluorescently
      tagged AChR or rapsyn in zebrafish larvae revealed that rapsyn self-clusters
      separate from AChRs did not exist before synapse formation. Examination of rapsyn
      in the AChR-less mutant sofa potato revealed that rapsyn in the absence of AChR
      was localized in the Golgi complex. Expression of muscle-type AChR in sofa potato
      restored synaptic clustering of rapsyn, while neuronal type AChR had no effect.
      To determine whether this requirement of protein interaction is reciprocal, we
      examined the mutant twitch once, which has a missense mutation in rapsyn. While
      the AChRs distributed nonsynaptically on the plasma membrane in twitch once,
      mutant rapsyn was retained in the Golgi complex. We conclude that AChRs enable
      the transport of rapsyn from the Golgi complex to the plasma membrane through a
      molecule-specific interaction.

PMID- 22623682
TI  - Modulatory effects of metabotropic glutamate receptors on local cortical
      circuits.
AB  - Glutamatergic pathways in various thalamic and cortical circuits have been
      classified into two types: Class 1 and Class 2, where it has been suggested that
      Class 1 carries the main information for processing, and Class 2 is mainly
      modulatory. We now extend this to the local circuitry of visual cortex of the
      mouse by demonstrating the modulatory actions on the Class 1 pathway from layer 4
      to layers 2/3 of a Class 2 input from adjacent locations in layers 2/3. We found
      that this Class 2 input produces a long-lasting hyperpolarization and suppresses
      the initial responses of input from layer 4 and that this involves the
      postsynaptic activation of Group II metabotropic glutamate receptors. This
      modulation also shifts the paired pulse ratio of the layer 4 input from
      depression to facilitation.

PMID- 22623683
TI  - Running speed alters the frequency of hippocampal gamma oscillations.
AB  - Successful spatial navigation is thought to employ a combination of at least two
      strategies: the following of landmark cues and path integration. Path integration
      requires that the brain use the speed and direction of movement in a meaningful
      way to continuously compute the position of the animal. Indeed, the running speed
      of rats modulates both the firing rate of neurons and the spectral properties of
      low frequency, theta oscillations seen in the local field potential (LFP) of the
      hippocampus, a region important for spatial memory formation. Higher frequency,
      gamma-band LFP oscillations are usually associated with decision-making,
      increased attention, and improved reaction times. Here, we show that increased
      running speed is accompanied by large, systematic increases in the frequency of
      hippocampal CA1 network oscillations spanning the entire gamma range (30-120 Hz)
      and beyond. These speed-dependent changes in frequency are seen on both linear
      tracks and two-dimensional platforms, and are thus independent of the behavioral
      task. Synchrony between anatomically distant CA1 regions also shifts to higher
      gamma frequencies as running speed increases. The changes in frequency are
      strongly correlated with changes in the firing rates of individual interneurons,
      consistent with models of gamma generation. Our results suggest that as a rat
      runs faster, there are faster gamma frequency transitions between sequential
      place cell-assemblies. This may help to preserve the spatial specificity of place
      cells and spatial memories at vastly different running speeds.

PMID- 22623684
TI  - Muscle coordination is habitual rather than optimal.
AB  - When sharing load among multiple muscles, humans appear to select an optimal
      pattern of activation that minimizes costs such as the effort or variability of
      movement. How the nervous system achieves this behavior, however, is unknown.
      Here we show that contrary to predictions from optimal control theory, habitual
      muscle activation patterns are surprisingly robust to changes in limb
      biomechanics. We first developed a method to simulate joint forces in real time
      from electromyographic recordings of the wrist muscles. When the model was
      altered to simulate the effects of paralyzing a muscle, the subjects simply
      increased the recruitment of all muscles to accomplish the task, rather than
      recruiting only the useful muscles. When the model was altered to make the force
      output of one muscle unusually noisy, the subjects again persisted in recruiting
      all muscles rather than eliminating the noisy one. Such habitual coordination
      patterns were also unaffected by real modifications of biomechanics produced by
      selectively damaging a muscle without affecting sensory feedback. Subjects
      naturally use different patterns of muscle contraction to produce the same forces
      in different pronation-supination postures, but when the simulation was based on
      a posture different from the actual posture, the recruitment patterns tended to
      agree with the actual rather than the simulated posture. The results appear
      inconsistent with computation of motor programs by an optimal controller in the
      brain. Rather, the brain may learn and recall command programs that result in
      muscle coordination patterns generated by lower sensorimotor circuitry that are
      functionally "good-enough."

PMID- 22623685
TI  - Selectively silencing GSK-3 isoforms reduces plaques and tangles in mouse models
      of Alzheimer's disease.
AB  - Glycogen synthase kinase-3 (GSK-3) is linked to the pathogenesis of Alzheimer's
      disease (AD), senile plaques (SPs), and neurofibrillary tangles (NFTs), but the
      specific contributions of each of the GSK-3 alpha and beta isoforms to mechanisms
      of AD have not been clarified. In this study, we sought to elucidate the role of
      each GSK-3alpha and GSK-3beta using novel viral and genetic approaches. First, we
      developed recombinant adeno-associated virus 2/1 short hairpin RNA constructs
      which specifically reduced expression and activity of GSK-3alpha or GSK-3beta.
      These constructs were injected intraventricularly in newborn AD transgenic (tg)
      mouse models of SPs (PDAPP+/-), both SPs and NFTs (PDAPP+/-;PS19+/-), or wild
      type controls. We found that knockdown (KD) of GSK-3alpha, but not GSK-3beta,
      reduced SP formation in PDAPP+/- and PS19+/-;PDAPP+/- tg mice. Moreover, both GSK
      3alpha and GSK-3beta KD reduced tau phosphorylation and tau misfolding in PS19+/
      ;PDAPP+/- mice. Next, we generated triple tg mice using the CaMKIIalpha-Cre
      (alpha-calcium/calmodulin-dependent protein kinase II-Cre) system to KD GSK
      3alpha in PDAPP+/- mice for further study of the effects of GSK-3alpha reduction
      on SP formation. GSK-3alpha KD showed a significant effect on reducing SPs and
      ameliorating memory deficits in PDAPP+/- mice. Together, the data from both
      approaches suggest that GSK-3alpha contributes to both SP and NFT pathogenesis
      while GSK-3beta only modulates NFT formation, suggesting common but also
      different targets for both isoforms. These findings highlight the potential
      importance of GSK-3alpha as a possible therapeutic target for ameliorating
      behavioral impairments linked to AD SPs and NFTs.

PMID- 22623687
TI  - Science to practice: why follow the track of macrophages in obesity?

PMID- 22623688
TI  - Falling prey to the sunk cost bias: a potential harm of patient radiation dose
      histories.

PMID- 22623686
TI  - LTP induction translocates cortactin at distant synapses in wild-type but not
      Fmr1 knock-out mice.
AB  - Stabilization of long-term potentiation (LTP) depends on reorganization of the
      dendritic spine actin cytoskeleton. The present study tested whether this
      involves activity-driven effects on the actin-regulatory protein cortactin, and
      whether such effects are disturbed in the Fmr1 knock-out (KO) model of fragile X
      syndrome, in which stabilization of both actin filaments and LTP is impaired. LTP
      induced by theta burst stimulation (TBS) in hippocampal slices from wild-type
      mice was associated with rapid, broadly distributed, and NMDA receptor-dependent
      decreases in synapse-associated cortactin. The reduction in cortactin content was
      blocked by blebbistatin, while basal levels were reduced by nocodazole,
      indicating that cortactin's movements into and away from synapses are regulated
      by microtubule and actomyosin motors, respectively. These results further suggest
      that synapse-specific LTP influences cytoskeletal elements at distant
      connections. The rapid effects of TBS on synaptic cortactin content were absent
      in Fmr1 KOs as was evidence for activity-driven phosphorylation of the protein or
      its upstream kinase, ERK1/2. Phosphorylation regulates cortactin's interactions
      with actin, and coprecipitation of the two proteins was reduced in the KOs. We
      propose that, in the KOs, excessive basal phosphorylation of ERK1/2 disrupts its
      interactions with cortactin, thereby blocking the latter protein's use of
      actomyosin transport systems. These impairments are predicted to compromise the
      response of the subsynaptic cytoskeleton to learning-related afferent activity,
      both locally and at distant sites.

PMID- 22623689
TI  - The Lazarus syndrome: the ethics of evidence-based versus experience-based
      medicine.

PMID- 22623691
TI  - Imaging evaluation of adult spinal injuries: emphasis on multidetector CT in
      cervical spine trauma.
AB  - As computed tomography (CT) technology has evolved, multidetector CT has become
      an integral part of the initial assessment of many injured patients, and the
      spine is easily included in the total body screening performed in patients with
      severe blunt polytrauma. Despite all the advantages of multidetector CT, clearing
      the spine in which injury is suspected continues to be a daily challenge in
      clinical practice. The purpose of this review is to present the evidence and the
      controversies surrounding the practice of imaging in patients suspected of having
      spine injury. The discussion is centered on the increasing reliance on
      multidetector CT in the work-up of these patients but also considers the
      important contributions of clinical trials to select patient for appropriate
      imaging on the basis of risk and probability of injury. Available protocols,
      injury classification systems, and issues awaiting future research are addressed.

PMID- 22623690
TI  - Molecular body imaging: MR imaging, CT, and US. part I. principles.
AB  - Molecular imaging, generally defined as noninvasive imaging of cellular and
      subcellular events, has gained tremendous depth and breadth as a research and
      clinical discipline in recent years. The coalescence of major advances in
      engineering, molecular biology, chemistry, immunology, and genetics has fueled
      multi- and interdisciplinary innovations with the goal of driving clinical
      noninvasive imaging strategies that will ultimately allow disease identification,
      risk stratification, and monitoring of therapy effects with unparalleled
      sensitivity and specificity. Techniques that allow imaging of molecular and
      cellular events facilitate and go hand in hand with the development of molecular
      therapies, offering promise for successfully combining imaging with therapy.
      While traditionally nuclear medicine imaging techniques, in particular positron
      emission tomography (PET), PET combined with computed tomography (CT), and single
      photon emission computed tomography, have been the molecular imaging methods most
      familiar to clinicians, great advances have recently been made in developing
      imaging techniques that utilize magnetic resonance (MR), optical, CT, and
      ultrasonographic (US) imaging. In the first part of this review series, we
      present an overview of the principles of MR imaging-, CT-, and US-based molecular
      imaging strategies.

PMID- 22623692
TI  - Locally advanced breast cancer: MR imaging for prediction of response to
      neoadjuvant chemotherapy--results from ACRIN 6657/I-SPY TRIAL.
AB  - PURPOSE: To compare magnetic resonance (MR) imaging findings and clinical
      assessment for prediction of pathologic response to neoadjuvant chemotherapy
      (NACT) in patients with stage II or III breast cancer. MATERIALS AND METHODS: The
      HIPAA-compliant protocol and the informed consent process were approved by the
      American College of Radiology Institutional Review Board and local-site
      institutional review boards. Women with invasive breast cancer of 3 cm or greater
      undergoing NACT with an anthracycline-based regimen, with or without a taxane,
      were enrolled between May 2002 and March 2006. MR imaging was performed before
      NACT (first examination), after one cycle of anthracyline-based treatment (second
      examination), between the anthracycline-based regimen and taxane (third
      examination), and after all chemotherapy and prior to surgery (fourth
      examination). MR imaging assessment included measurements of tumor longest
      diameter and volume and peak signal enhancement ratio. Clinical size was also
      recorded at each time point. Change in clinical and MR imaging predictor
      variables were compared for the ability to predict pathologic complete response
      (pCR) and residual cancer burden (RCB). Univariate and multivariate random
      effects logistic regression models were used to characterize the ability of tumor
      response measurements to predict pathologic outcome, with area under the receiver
      operating characteristic curve (AUC) used as a summary statistic. RESULTS: Data
      in 216 women (age range, 26-68 years) with two or more imaging time points were
      analyzed. For prediction of both pCR and RCB, MR imaging size measurements were
      superior to clinical examination at all time points, with tumor volume change
      showing the greatest relative benefit at the second MR imaging examination. AUC
      differences between MR imaging volume and clinical size predictors at the early,
      mid-, and posttreatment time points, respectively, were 0.14, 0.09, and 0.02 for
      prediction of pCR and 0.09, 0.07, and 0.05 for prediction of RCB. In multivariate
      analysis, the AUC for predicting pCR at the second imaging examination increased
      from 0.70 for volume alone to 0.73 when all four predictor variables were used.
      Additional predictive value was gained with adjustments for age and race.
      CONCLUSION: MR imaging findings are a stronger predictor of pathologic response
      to NACT than clinical assessment, with the greatest advantage observed with the
      use of volumetric measurement of tumor response early in treatment.

PMID- 22623693
TI  - Chemical shift MR imaging methods for the quantification of transcatheter
      lipiodol delivery to the liver: preclinical feasibility studies in a rodent
      model.
AB  - PURPOSE: To demonstrate the feasibility of using chemical shift magnetic
      resonance (MR) imaging fat-water separation methods for quantitative estimation
      of transcatheter lipiodol delivery to liver tissues. MATERIALS AND METHODS:
      Studies were performed in accordance with institutional Animal Care and Use
      Committee guidelines. Proton nuclear MR spectroscopy was first performed to
      identify lipiodol spectral peaks and relative amplitudes. Next, phantoms were
      constructed with increasing lipiodol-water volume fractions. A multiecho chemical
      shift-based fat-water separation method was used to quantify lipiodol
      concentration within each phantom. Six rats served as controls; 18 rats underwent
      catheterization with digital subtraction angiography guidance for intraportal
      infusion of a 15%, 30%, or 50% by volume lipiodol-saline mixture. MR imaging
      measurements were used to quantify lipiodol delivery to each rat liver. Lipiodol
      concentration maps were reconstructed by using both single-peak and multipeak
      chemical shift models. Intraclass and Spearman correlation coefficients were
      calculated for statistical comparison of MR imaging-based lipiodol concentration
      and volume measurements to reference standards (known lipiodol phantom
      compositions and the infused lipiodol dose during rat studies). RESULTS: Both
      single-peak and multipeak measurements were well correlated to phantom lipiodol
      concentrations (r(2) > 0.99). Lipiodol volume measurements were progressively and
      significantly higher when comparing between animals receiving different doses (P
      < .05 for each comparison). MR imaging-based lipiodol volume measurements
      strongly correlated with infused dose (intraclass correlation coefficients >
      0.93, P < .001) with both single- and multipeak approaches. CONCLUSION: Chemical
      shift MR imaging fat-water separation methods can be used for quantitative
      measurements of lipiodol delivery to liver tissues.

PMID- 22623694
TI  - Pancreatic adenocarcinoma: variability of diffusion-weighted MR imaging findings.
AB  - PURPOSE: To compare the apparent diffusion coefficients (ADCs) of pancreatic
      adenocarcinomas that appear hyperintense with clearly defined borders (clear
      hyperintense) with those that do not show clear hyperintense borders on diffusion
      weighted magnetic resonance (MR) images. MATERIALS AND METHODS: Institutional
      review board approval was obtained and informed consent was waived. Eighty
      patients with histologically confirmed pancreatic adenocarcinoma (mean tumor
      size, 32 mm) underwent fat-suppressed single-shot echo-planar 3.0-T diffusion
      weighted MR imaging with diffusion gradients (b = 1000 sec/mm(2)). ADC values of
      the pancreatic adenocarcinomas (n = 80) and proximal (n = 51) and distal (n = 70)
      pancreas were compared by using the Friedman test, followed by the Wilcoxon
      signed-rank test, and the difference in serum amylase levels between pancreatic
      adenocarcinomas with and without clear hyperintensity was evaluated by using the
      x(2) test. RESULTS: In 38 of 80 patients, pancreatic adenocarcinomas showed clear
      hyperintensity relative to the surrounding pancreas; 26 were hyperintense with
      unclear distal borders; 12, isointense; and four, hypointense. In all patients,
      the mean ADC (+/- standard deviation) of the tumors (1.16 * 10(-3) mm(2)/sec +/-
      0.22) was significantly lower than those of the proximal pancreas (1.33 * 10(-3)
      mm(2)/sec +/- 0.16, P < .001) and the distal pancreatic parenchyma (1.24 * 10(-3)
      mm(2)/sec +/- 0.23, P = .004). No significant difference in ADC was seen between
      the pancreatic adenocarcinomas without clear hyperintensity and the distal
      pancreas. The frequency of serum amylase levels greater than 120 U/L (2.00
      MUkat/L) was significantly higher than in those with clear hyperintense
      pancreatic adenocarcinomas (P < .001). CONCLUSION: Diffusion-weighted MR imaging
      was not useful for delineating 47% of pancreatic adenocarcinomas, because of
      hyperintensity of the pancreatic parenchyma distal to the cancer.

PMID- 22623695
TI  - Tibial stress injury: relationship of radiographic, nuclear medicine bone
      scanning, MR imaging, and CT Severity grades to clinical severity and time to
      healing.
AB  - PURPOSE: To examine the relationship between severity grade for radiography,
      triple-phase technetium 99m nuclear medicine bone scanning, magnetic resonance
      (MR) imaging, and computed tomography (CT); clinical severity; and recovery time
      from a tibial stress injury (TSI), as well as to evaluate interassessor grading
      reliability. MATERIALS AND METHODS: This protocol was approved by the Griffith
      University Human Research Ethics Committee, the Stanford University Panel on
      Human Subjects in Medical Research, the U.S. Army Human Subjects Research Review
      Board, and the Australian Defense Human Research Ethics Committee. Informed
      consent was obtained from all subjects. Forty subjects (17 men, 23 women; mean
      age, 26.2 years +/- 6.9 [standard deviation]) with TSI were enrolled. Subjects
      were examined acutely with standard anteroposterior and lateral radiography,
      nuclear medicine scanning, MR imaging, and CT. Each modality was graded by four
      blinded clinicians. Mixed-effects models were used to examine associations
      between image severity, clinical severity, and time to healing, with adjustments
      for image modality and assessor. Grading reliability was evaluated with the
      Cronbach alpha coefficient. RESULTS: Image assessment reliability was high for
      all grading systems except radiography, which was moderate (alpha = 0.565-0.895).
      Clinical severity was negatively associated with MR imaging severity (P <= .001).
      There was no significant relationship between time to healing and severity score
      for any imaging modality, although a positive trend existed for MR imaging (P =
      .07). CONCLUSION: TSI clinical severity was negatively related to MR imaging
      severity. Radiographic, bone scan, and CT severity were not related to time to
      healing, but there was a positive trend for MR imaging.

PMID- 22623696
TI  - Endovascular treatment of intracranial unruptured aneurysms: a systematic review
      of the literature on safety with emphasis on subgroup analyses.
AB  - PURPOSE: To report subgroup analyses of an updated systematic review on
      endovascular treatment of intracranial unruptured aneurysms (UAs); to compare
      types of embolic agents, adjunct techniques, and newer devices; and to identify
      potential risk factors for poor outcomes. MATERIALS AND METHODS: Meta-Analysis of
      Observational Studies in Epidemiology and Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guidelines were used to prepare this
      article, and the literature was searched with PubMed and with EMBASE and Cochrane
      databases. Six eligibility criteria (procedural complications rates; at least 10
      patients; saccular, nondissecting UAs; original study published in English or
      French between January 2003 and July 2011; methodological quality score > 6
      [modified Strengthening and Reporting of Observational Studies in Epidemiology
      criteria]; a study published in a peer-reviewed journal) were used. End points
      included procedural mortality and unfavorable outcomes (death or modified Rankin
      Scale, Glasgow Outcome Scale, or World Federation of Neurosurgeons Scale at 1
      month scores, all > 2). A fixed-effects model (Mantel-Haenszel) was used for
      pooled estimates of mortality and unfavorable outcomes; a random-effects model
      (DerSimonian-Laird) was used in case of heterogeneity. RESULTS: Ninety-seven
      studies with 7172 patients (26 studies published July 2008 through July 2011)
      were included. Sixty-nine (1.8%) of 7034 patients died (fixed-effect weighted
      average; 99% confidence interval [CI]: 1.4%, 2.4%; Q value, 55.0; I(2) = 0%).
      Unfavorable outcomes, including death, occurred in 4.7% (242 of 6941) of patients
      (99% CI: 3.8, 5.7; Q value, 128.3; I(2) = 26.8%). Patients treated after 2004 had
      better outcomes (unfavorable outcome, 3.1; 99% CI: 2.4, 4.0) than patients
      treated during 2001-2003 (unfavorable outcome, 4.7%; 99% CI: 3.6%, 6.1%; P = .01)
      or in 2000 and before (unfavorable outcome, 5.6%; 99% CI: 4.7%, 6.6%; P < .001).
      Significantly higher risk was associated with liquid embolic agents (8.1%; 99%
      CI: 4.7%, 13.7%) versus simple coil placement (4.9%; 99% CI: 3.8%, 6.3%; P =
      .002). Unfavorable outcomes occurred in 11.5% (99% CI: 4.9%, 24.6%) of patients
      treated with flow diversion. CONCLUSION: Procedure-related poor outcomes occurred
      (4.7% of patients), risks decreased, and liquid embolic agents and flow diversion
      were associated with higher risks.

PMID- 22623697
TI  - Brown fat at PET/CT: correlation with patient characteristics.
AB  - PURPOSES: To assess the prevalence of brown fat in patients with cancer, compare
      demographic characteristics of those with and those without brown fat, and
      correlate these characteristics with the mean and maximum standardized uptake
      values of brown fat. MATERIALS AND METHODS: This case-control study was
      institutional review board approved and HIPAA compliant. Informed consent was
      waived. Reports of 12 195 consecutive positron emission tomography/computed
      tomography examinations performed in 6867 patients between January 2004 and
      November 2008 were reviewed for documented fluorodeoxyglucose (FDG) uptake in
      brown fat (n = 298). Control patients (n = 298) without brown fat were chosen and
      matched for age, sex, and month and year of examination. Age, sex, weight, body
      mass index, ethnicity, and examination stage (initial vs restaging) were compared
      between groups. Paired Student t test, chi(2) test, Pearson correlation
      coefficient, and analysis of variance were used for statistical analysis.
      RESULTS: Uptake of FDG in brown fat was demonstrated in 298 of 6867 (4.33%)
      patients. Prevalence of brown fat was significantly higher in female (5.9% [211
      of 3587]) than in male patients (2.65% [87 of 3280]; P < .001). Those with brown
      fat had significantly lower body weight (147.5 lb +/- 3.8 vs 168.61 lb +/- 5.0; P
      < .001) and body mass index (24.3 +/- 0.54 vs 27.6 +/- 0.77; P < .001) than
      control patients. There was no significant difference in the prevalence of brown
      fat among ethnic groups. The maximum standardized uptake value of brown fat had a
      significant inverse correlation with age (r = -0.3, P < .001). CONCLUSION:
      Patients with brown fat were more likely to be female and thinner than those
      without brown fat. Younger patients were more likely to have higher maximum
      standardized uptake values of brown fat.

PMID- 22623698
TI  - Combined quantification of liver perfusion and function with dynamic gadoxetic
      acid-enhanced MR imaging.
AB  - PURPOSE: To evaluate the feasibility of quantifying hepatic perfusion and
      function by using dynamic contrast material-enhanced (DCE) magnetic resonance
      (MR) imaging with the hepatobiliary contrast agent gadoxetic acid and a dual
      inlet two-compartment uptake model. MATERIALS AND METHODS: The study was approved
      by the local institutional review board, and written informed consent was
      obtained from all patients. Data were acquired between October 2008 and November
      2009 in 24 patients with hepatic metastases from neuroendocrine tumors (13 men,
      11 women; mean age, 59.8 years). DCE MR imaging was performed at 3.0 T with a
      standard dose of gadoxetic acid and a three-dimensional sequence, with 48
      sections of data acquired every 2.2 seconds for 5 minutes. For each patient, a
      plasma flow map was calculated by means of deconvolution and the model was fitted
      to six region-of-interest curves. Results were evaluated with goodness-of-fit
      analysis and, in normal-appearing liver tissue, by comparing perfusion parameters
      with those reported in the literature. Interobserver effects in the selection of
      arterial and venous input functions were assessed. RESULTS: With an arterial
      delay parameter, the model provided a good fit to all data. Values for arterial
      and venous plasma flow and extracellular volume in normal-appearing liver tissue
      were comparable to those in the literature. The mean intracellular uptake rate is
      3.4/100/min with a standard deviation of 1.9/100/min The model also provided a
      good fit in all tumor data, producing high arterial flow fraction (87%) and lower
      uptake (1.7/100/min) . Bias due to observer-dependent differences in the
      selection of the input functions was negligible. CONCLUSION: The analysis of
      dynamic gadoxetic acid-enhanced MR images with the dual-inlet two-compartment
      uptake model presents a new and practical approach for measuring arterial and
      venous perfusion and hepatic function in a single acquisition.

PMID- 22623699
TI  - Time-resolved CT angiography for the detection and classification of endoleaks.
AB  - PURPOSE: To assess the feasibility and diagnostic performance of time-resolved
      computed tomographic (CT) angiography in the detection and classification of
      endoleaks after endovascular aortic aneurysm repair (EVAR) in high-risk patients.
      MATERIALS AND METHODS: The study was approved by our ethics committee. Written
      informed consent was obtained from all participating patients. Fifty-four
      patients (42 male and 12 female patients; mean age, 70.9 years +/- 9.3 [standard
      deviation]) with either thoracic (n = 8) or abdominal (n = 46) aortic aneurysms
      treated with a stent-graft were prospectively included. The patients were
      examined with a time-resolved CT angiographic protocol consisting of 12 low-dose
      phases (80 kVp; 120 mAs [effective]; scan range, 27 cm), with 60 mL of iomeprol.
      Patients with abdominal aneurysm repair also underwent contrast material-enhanced
      (CE) ultrasonography (US). The time delay between contrast enhancement within the
      stent lumen and the endoleak was measured. Effective radiation dose was
      calculated from the scanner protocols. Measures of diagnostic performance for the
      detection of endoleaks were calculated for time-resolved CT angiography, with CE
      US serving as the reference standard. RESULTS: All time-resolved CT angiographic
      data sets were diagnostic. Mean effective radiation dose was 14.6 mSv. Four
      thoracic and 19 abdominal endoleaks were identified by using time-resolved CT
      angiography. Seventeen of 19 abdominal endoleaks were confirmed with CE US. This
      rate resulted in a sensitivity of 94%, a specificity of 93%, a positive
      predictive value of 89%, and a negative predictive value of 96% for time-resolved
      CT angiography after abdominal EVAR. Type I endoleaks showed significantly
      earlier mean peak contrast enhancement (0.28 second +/- 0.83) compared with that
      for type II endoleaks (9.17 seconds +/- 3.59, P < .0001). CONCLUSION: Time
      resolved CT angiography with 12 low-dose phases is feasible for patients after
      thoracic and abdominal EVAR. The protocol approximates the radiation dose of
      standard triphasic protocols. Its dynamic information differentiates types of
      endoleaks and shows high diagnostic performance.

PMID- 22623701
TI  - Case 182: pulmonary amyloidosis.

PMID- 22623702
TI  - Prognostic value of coronary ct angiography for cardiac events.

PMID- 22623703
TI  - American college of radiology resident and fellow section web site.

PMID- 22623704
TI  - Reconstruction algorithms and CT emphysema measurements.

PMID- 22623705
TI  - Degraded diagnostic accuracy caused by coronary artery calcification.

PMID- 22623706
TI  - Low-dose scan protocols in dual-source CT coronary angiography.

PMID- 22623708
TI  - Height, sitting height, and leg length in relation with breast cancer risk in the
      E3N cohort.
AB  - BACKGROUND: If height is a well-established risk factor for breast cancer, leg
      length and sitting height are usually considered as better candidate biomarkers
      of growth hormone exposure than height, respectively, in pre- and postpuberty.
      METHODS: Risk of breast cancer associated with quartiles of height, sitting
      height, and leg length were estimated in the French E3N cohort (N = 50,704,
      including 2,065 breast cancer cases), stratified on both menopausal and hormone
      receptor statuses. RESULTS: Height was associated with an increased
      postmenopausal breast cancer risk [HR = 1.22 (1.06-1.41) when comparing extreme
      categories, P(trend) = 0.002], which was exclusively driven by the association
      with leg length [HR = 1.21 (1.05-1.39), P(trend) = 0.013] and not sitting height
      [HR = 1.03 (0.89-1.18), P(trend) = 0.379]. Leg length was associated with an
      increased ER(+) breast cancer risk in postmenopausal [HR = 1.24 (1.06-1.46),
      P(trend) = 0.004], whereas sitting height was associated with a borderline
      decreased ER(-) premenopausal breast cancer risk [HR = 0.45 (0.20-1.01), P(trend)
      = 0.011]. The positive associations observed in the overall population between
      leg length and breast cancer risk were actually restricted to women who had a
      short birth length [HR = 1.82 (1.22-2.72), P(trend) = 0.022] and those with a low
      birth weight [HR = 1.43 (1.00-2.04), P(trend) = 0.054]. CONCLUSION: The two
      components of height risk are differentially associated with breast cancer risk:
      leg length with an increased risk of postmenopausal ER(+) tumors and sitting
      height with a decreased risk of premenopausal ER(-) tumors. IMPACT: Future
      prospective studies should no longer consider height a single risk factor for
      breast cancer risk.

PMID- 22623707
TI  - Serum vitamin D and risk of bladder cancer in the Prostate, Lung, Colorectal, and
      Ovarian (PLCO) Cancer Screening trial.
AB  - BACKGROUND: The one previous prospective study of vitamin D status and risk of
      urinary bladder cancer found that male smokers with low serum 25-hydroxy-vitamin
      D [25(OH)D] were at a nearly two-fold increased risk. We conducted an analysis of
      serum 25(OH)D and risk of bladder cancer in the Prostate, Lung, Colorectal, and
      Ovarian (PLCO) Cancer Screening Study and examined whether serum vitamin D
      binding protein (DBP) concentration confounded or modified the association.
      METHODS: Three hundred and seventy-five cases of bladder cancer were matched 1:1
      with controls based on age (+/-5 years), race, sex, and date of blood collection
      (+/-30 days). Conditional logistic regression was used to estimate ORs and 95%
      confidence intervals (CI) of bladder cancer by prediagnosis levels of 25(OH)D.
      RESULTS: We found no strong or statistically significant association between
      serum 25(OH)D and bladder cancer risk (Q1 vs. Q4: OR, 0.84; 95% CI, 0.52-1.36;
      P(trend) = 0.56). Further adjustment for, or stratification by, serum DBP did not
      alter the findings, nor was there a main effect association between DBP and risk.
      CONCLUSION: In contrast to an earlier report, we observed no association between
      vitamin D status and risk of bladder cancer; this difference could be due to the
      inclusion of women and nonsmokers in the current study population or due to the
      differences in the distribution of vitamin D concentrations between the two study
      populations. IMPACT: These findings may contribute to future meta-analyses and
      help elucidate whether the vitamin D-bladder cancer association varies across
      populations.

PMID- 22623709
TI  - Placental weight and breast cancer risk in young women: a registry-based cohort
      study from Norway.
AB  - BACKGROUND: Pregnancy has a short-term risk-increasing effect on breast cancer
      that may be attributed to growth-promoting effects of pregnancy hormones on
      prevalent but undetected tumors. Results of two previous studies suggested that
      placental weight may be positively associated with breast cancer risk. METHODS:
      In a cohort of 338,051 women followed from 1999 to 2008, on the basis of data
      linkage between the Medical Birth Registry of Norway and the Cancer Registry of
      Norway, we assessed whether placental weight in a woman's most recent pregnancy
      was related to breast cancer risk during the first years following pregnancy.
      RESULTS: During follow-up (median, 6.0 years; interquartile range, 3.0-8.3
      years), 648 women were diagnosed with breast cancer at a mean age of 38.4 years
      (standard deviation, 5.3 years). Placental weight in the most recent pregnancy
      was not associated with breast cancer risk: the hazard ratio per 100-gram
      increase in placental weight was 1.03 [95% confidence interval, 0.96-1.10]. There
      was a similar lack of association related to mean placental weight across
      pregnancies and to placental weight associated with the first birth. CONCLUSION:
      We could not confirm previous reports that women who develop large placentas are
      at increased risk of breast cancer. IMPACT: The epidemiologic support for an
      association of placental weight with breast cancer risk remains inconclusive.
      More research is needed to identify factors that influence breast cancer risk in
      young women.

PMID- 22623711
TI  - Expression of the autoimmunity associated TNFAIP3 is increased in rheumatoid
      arthritis but does not differ according to genotype at 6q23.

PMID- 22623712
TI  - A rare case of homicidal insecticide (organochloro compound) poisoning by
      intraperitoneal injection.
AB  - We report a case of a 52-year-old businessman who was allegedly injected with
      organochloro compound (OC) in his abdomen by his business rivals by means of a
      surgical needle and a syringe. Homicide by OC injection via an intraperitoneal
      route has not been reported in the literature. Postmortem findings along with the
      toxicology report have been discussed particularly in view of the mode of poison
      administration with a review of literature.

PMID- 22623710
TI  - The MTAP-CDKN2A locus confers susceptibility to a naturally occurring canine
      cancer.
AB  - BACKGROUND: Advantages offered by canine population substructure, combined with
      clinical presentations similar to human disorders, makes the dog an attractive
      system for studies of cancer genetics. Cancers that have been difficult to study
      in human families or populations are of particular interest. Histiocytic sarcoma
      is a rare and poorly understood neoplasm in humans that occurs in 15% to 25% of
      Bernese Mountain Dogs (BMD). METHODS: Genomic DNA was collected from affected and
      unaffected BMD in North America and Europe. Both independent and combined genome
      wide association studies (GWAS) were used to identify cancer-associated loci.
      Fine mapping and sequencing narrowed the primary locus to a single gene region.
      RESULTS: Both populations shared the same primary locus, which features a single
      haplotype spanning MTAP and part of CDKN2A and is present in 96% of affected BMD.
      The haplotype is within the region homologous to human chromosome 9p21, which has
      been implicated in several types of cancer. CONCLUSIONS: We present the first
      GWAS for histiocytic sarcoma in any species. The data identify an associated
      haplotype in the highly cited tumor suppressor locus near CDKN2A. These data show
      the power of studying distinctive malignancies in highly predisposed dog breeds.
      IMPACT: Here, we establish a naturally occurring model of cancer susceptibility
      due to CDKN2 dysregulation, thus providing insight about this cancer-associated,
      complex, and poorly understood genomic region.

PMID- 22623713
TI  - Exploration of staff attitudes and experiences towards mixed- and single-sex
      wards in the National Secure Forensic Service for Young People.
AB  - Mixed-sex wards in adult forensic secure services have been abolished and
      replaced by single-sex services. The National Secure Forensic Service for Young
      People (NSFSYP) continues to use a mixture of single-sex male and mixed-sex
      wards. This study aimed to explore staff experiences and attitudes towards
      placing young people in mixed- or single-sex wards in the NSFSYP. Mixed
      methodology was adopted in the form of focus groups (qualitative) and
      questionnaires (semi-quantitative). Content analyses of the qualitative data
      revealed five themes: care of female patients, normalization, safety,
      commissioning and social representation of women. The questionnaire was developed
      from the qualitative findings and comprised 22 statements measuring attitudes
      towards mixed- and single-sex wards. One hundred and forty-five questionnaires
      were returned: a 44% total response rate. Overall, the responses to the
      questionnaire confirmed the focus group data. There were statistically
      significant differences in responses between staff working on mixed- and single
      sex wards. Staff working on mixed-sex wards felt that mixing genders on wards is
      a crucial part of adolescent forensic inpatient treatment. For them, mixed wards
      provide a more developmentally appropriate environment for young people. The
      needs of female patients broaden the debate beyond segregating and mixing gender.

PMID- 22623714
TI  - Dermatoses misdiagnosed as deliberate injuries.
AB  - Examination of non-accidental injuries on a body should be done with caution, as
      often skin diseases can mimic deliberate injuries. Patients with active
      dermatoses or their residual/post-inflammatory spots seen during autopsy can
      generate false alarms or suspicion of burns, child abuse or battering, sexual
      assault or other medicolegal cases. The inability to distinguish between a
      mechanical injury and skin disease can cause unnecessary anxiety and can
      complicate medicolegal investigations. Many times, an elaborate history to find
      out the aetiology of the lesion is either unavailable or not reliable as in the
      cases of young children, insane or mentally subnormal patients or in medicolegal
      deaths. The greatest chance of misinterpretation may be in cases of extensive
      denudation of the skin seen in severe drug reactions like toxic epidermal
      necrolysis, which can be mistaken for scald burns. Other important cases include
      bruises diagnosed on seeing discoloured spots on the skin or genital lesions
      raising the suspicion of sexual abuse in children. This diagnostic dilemma can
      also lead to undue forensic investigations, imprecise expert opinions and
      distress to patients or their family members. This review aims to generate
      awareness about proper interpretation of findings with an open mind, the clues to
      differentiate between true and false injuries and the management thereof.

PMID- 22623715
TI  - High-sensitivity cardiac troponin in the distinction of acute myocardial
      infarction from acute cardiac noncoronary artery disease.
AB  - BACKGROUND: We hypothesized that high-sensitivity cardiac troponin (hs-cTn) and
      its early change are useful in distinguishing acute myocardial infarction (AMI)
      from acute cardiac noncoronary artery disease. METHODS AND RESULTS: In a
      prospective, international multicenter study, hs-cTn was measured with 3 assays
      (hs-cTnT, Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI Siemens) in a
      blinded fashion at presentation and serially thereafter in 887 unselected
      patients with acute chest pain. Accuracy of the combination of presentation
      values with serial changes was compared against a final diagnosis adjudicated by
      2 independent cardiologists. AMI was the adjudicated final diagnosis in 127
      patients (15%); cardiac noncoronary artery disease, in 124 (14%). Patients with
      AMI had higher median presentation values of hs-cTnT (0.113 MUg/L [interquartile
      range, 0.049-0.246 MUg/L] versus 0.012 MUg/L [interquartile range, 0.006-0.034
      MUg/L]; P<0.001) and higher absolute changes in hs-cTnT in the first hour (0.019
      MUg/L [interquartile range, 0.007-0.067 MUg/L] versus 0.001 MUg/L [interquartile
      range, 0-0.003 MUg/L]; P<0.001) than patients with cardiac noncoronary artery
      disease. Similar findings were obtained with the hs-cTnI assays. Adding changes
      of hs-cTn in the first hour to its presentation value yielded a diagnostic
      accuracy for AMI as quantified by the area under the receiver-operating
      characteristics curve of 0.94 for hs-cTnT (0.92 for both hs-cTnI assays).
      Algorithms using ST-elevation, presentation values, and changes in hs-cTn in the
      first hour accurately separated patients with AMI and those with cardiac
      noncoronary artery disease. These findings were confirmed when the final
      diagnosis was readjudicated with the use of hs-cTnT values and validated in an
      independent validation cohort. CONCLUSION: The combined use of hs-cTn at
      presentation and its early absolute change excellently discriminates between
      patients with AMI and those with cardiac noncoronary artery disease. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00470587.

PMID- 22623716
TI  - Chest compression rate: where is the sweet spot?

PMID- 22623717
TI  - Relationship between chest compression rates and outcomes from cardiac arrest.
AB  - BACKGROUND: Guidelines for cardiopulmonary resuscitation recommend a chest
      compression rate of at least 100 compressions per minute. Animal and human
      studies have reported that blood flow is greatest with chest compression rates
      near 120/min, but few have reported rates used during out-of-hospital (OOH)
      cardiopulmonary resuscitation or the relationship between rate and outcome. The
      purpose of this study was to describe chest compression rates used by emergency
      medical services providers to resuscitate patients with OOH cardiac arrest and to
      determine the relationship between chest compression rate and outcome. METHODS
      AND RESULTS: Included were patients aged >= 20 years with OOH cardiac arrest
      treated by emergency medical services providers participating in the
      Resuscitation Outcomes Consortium. Data were abstracted from monitor
      defibrillator recordings during cardiopulmonary resuscitation. Multiple logistic
      regression analysis assessed the association between chest compression rate and
      outcome. From December 2005 to May 2007, 3098 patients with OOH cardiac arrest
      were included in this study. Mean age was 67 +/- 16 years, and 8.6% survived to
      hospital discharge. Mean compression rate was 112 +/- 19/min. A curvilinear
      association between chest compression rate and return of spontaneous circulation
      was found in cubic spline models after multivariable adjustment (P=0.012). Return
      of spontaneous circulation rates peaked at a compression rate of ~ 125/min and
      then declined. Chest compression rate was not significantly associated with
      survival to hospital discharge in multivariable categorical or cubic spline
      models. CONCLUSIONS: Chest compression rate was associated with return of
      spontaneous circulation but not with survival to hospital discharge in OOH
      cardiac arrest.

PMID- 22623718
TI  - Association between family history and coronary heart disease death across long
      term follow-up in men: the Cooper Center Longitudinal Study.
AB  - BACKGROUND: Family history of coronary heart disease (CHD) has been well studied
      as an independent risk factor for CHD events in the short term (<10 years).
      However, data are sparse on the association between family history and risk for
      CHD across long-term follow-up. METHODS AND RESULTS: We included 49 255 men from
      the Cooper Center Longitudinal Study. Premature family history of CHD was defined
      as the presence of angina, myocardial infarction, angioplasty, or bypass surgery
      in a relative <50 years of age. Cause-specific mortality was obtained from the
      National Death Index. The association between premature family history and
      cardiovascular disease (CVD) or CHD death was compared across 3 unique follow-up
      periods (0-10, >10-20, and >20 years). Lifetime risk was estimated by use of a
      modified survival analytic technique adjusted for competing risk with non-CVD
      death as the competing event. After 811 708 person-years of follow-up, there were
      919 CHD deaths and 1456 CVD deaths. After adjustment for traditional risk
      factors, premature family history was associated with CHD mortality >10 to 20
      years (1.59; 95% confidence interval, 1.14-2.22) and >20 years (1.43; 95%
      confidence interval, 1.05-1.95) with wider confidence intervals at 0 to 10 years
      (1.32; 95% confidence interval, 0.76-2.31). Similar findings were observed for
      CVD mortality. Compared with men without a family history of coronary artery
      disease, premature family history was associated with an ~50% higher lifetime
      risk for both CHD and CVD mortality (13.7% versus 8.9% and 21% versus 14.1%,
      respectively). CONCLUSION: Premature family history was associated with a
      persistent increase in both CHD and CVD mortality risk across long-term follow
      up, resulting in significantly higher lifetime risk estimates.

PMID- 22623719
TI  - Sho1p connects the plasma membrane with proteins of the cytokinesis network
      through multiple isomeric interaction states.
AB  - An understanding of cytokinesis at the molecular level requires a detailed
      description of the protein complexes that perform central activities during this
      process. The proteins Hof1p, Cyk3p, Inn1p and Myo1p each represent one of the
      four genetically defined and partially complementary pathways of cytokinesis in
      the yeast Saccharomyces cerevisiae. Here we show that the osmosensor Sho1p is
      required for correct cell-cell separation. Shortly before cytokinesis Sho1p
      sequentially assembles with Hof1p, Inn1p and Cyk3p, into a complex (the HICS
      complex) that might help to connect the membrane with the actin-myosin ring. The
      HICS complex is formed exclusively through interactions between three SH3 domains
      located in Cyk3p, Hof1p and Sho1p, and five acceptor sites found in Cyk3p, Hof1p
      and Inn1p. Owing to the overlapping binding specificities of its members the HICS
      complex is best described as ensembles of isomeric interaction states that
      precisely coordinate the different functions of the interactors during
      cytokinesis.

PMID- 22623722
TI  - Restoration of the intrinsic properties of human dermal papilla in vitro.
AB  - The dermal papilla (DP) plays pivotal roles in hair follicle morphogenesis and
      cycling. However, characterization and/or propagation of human DPs have been
      unsatisfactory because of the lack of efficient isolation methods and the loss of
      innate characteristics in vitro. We hypothesized that culture conditions
      sustaining the intrinsic molecular signature of the human DP could facilitate
      expansion of functional DP cells. To test this, we first characterized the global
      gene expression profile of microdissected, non-cultured human DPs. We performed a
      'two-step' microarray analysis to exclude the influence of unwanted contaminants
      in isolated DPs and successfully identified 118 human DP signature genes,
      including 38 genes listed in the mouse DP signature. The bioinformatics analysis
      of the DP gene list revealed that WNT, BMP and FGF signaling pathways were
      upregulated in intact DPs and addition of 6-bromoindirubin-3'-oxime, recombinant
      BMP2 and basic FGF to stimulate these respective signaling pathways resulted in
      maintained expression of in situ DP signature genes in primarily cultured human
      DP cells. More importantly, the exposure to these stimulants restored normally
      reduced DP biomarker expression in conventionally cultured DP cells. Cell growth
      was moderate in the newly developed culture medium. However, rapid DP cell
      expansion by conventional culture followed by the restoration by defined
      activators provided a sufficient number of DP cells that demonstrated
      characteristic DP activities in functional assays. The study reported here
      revealed previously unreported molecular mechanisms contributing to human DP
      properties and describes a useful technique for the investigation of human DP
      biology and hair follicle bioengineering.

PMID- 22623721
TI  - The C. elegans F-box proteins LIN-23 and SEL-10 antagonize centrosome duplication
      by regulating ZYG-1 levels.
AB  - The correct segregation of DNA during cell division requires formation of a
      bipolar spindle, organized at each pole by a centrosome. The regulation of
      centrosome duplication such that each mitotic cell has exactly two centrosomes is
      therefore of central importance to cell division. Deregulation of centrosome
      duplication causes the appearance of supernumerary centrosomes, which are a
      hallmark of many cancer cells and can contribute to tumorigenesis. Overexpression
      of the kinase Plk4, which is required for centrosome duplication, causes the
      formation of extra centrosomes, and aberrant Plk4 expression levels are
      associated with cancer. Data from Drosophila and human cells show that Plk4
      levels are regulated by the SCF ubiquitin ligase and proteasomal degradation.
      Recognition of Plk4 by the SCF complex is mediated by the F-box protein
      Slimb/betaTrCP. We show that levels of the C. elegans Plk4 homolog ZYG-1 are
      elevated by impairing proteasome or SCF function, indicating that ZYG-1 is
      regulated by a conserved mechanism. In C. elegans, similar to Drosophila and
      humans, we find that the Slimb/betaTrCP homolog LIN-23 regulates ZYG-1 levels. In
      addition, we show that a second F-box protein, SEL-10, also contributes to ZYG-1
      regulation. Co-depletion of LIN-23 and SEL-10 suggests these proteins function
      cooperatively. Because SEL-10 is the homolog of human FBW7, which is frequently
      mutated in cancer, our findings have implications for understanding
      tumorigenesis.

PMID- 22623720
TI  - CAS-1, a C. elegans cyclase-associated protein, is required for sarcomeric actin
      assembly in striated muscle.
AB  - Assembly of contractile apparatuses in striated muscle requires precisely
      regulated reorganization of the actin cytoskeletal proteins into sarcomeric
      organization. Regulation of actin filament dynamics is one of the essential
      processes of myofibril assembly, but the mechanism of actin regulation in
      striated muscle is not clearly understood. Actin depolymerizing factor
      (ADF)/cofilin is a key enhancer of actin filament dynamics in striated muscle in
      both vertebrates and nematodes. Here, we report that CAS-1, a cyclase-associated
      protein in Caenorhabditis elegans, promotes ADF/cofilin-dependent actin filament
      turnover in vitro and is required for sarcomeric actin organization in striated
      muscle. CAS-1 is predominantly expressed in striated muscle from embryos to
      adults. In vitro, CAS-1 binds to actin monomers and enhances exchange of actin
      bound ATP/ADP even in the presence of UNC-60B, a muscle-specific ADF/cofilin that
      inhibits the nucleotide exchange. As a result, CAS-1 and UNC-60B cooperatively
      enhance actin filament turnover. The two proteins also cooperate to shorten actin
      filaments. A cas-1 mutation is homozygous lethal with defects in sarcomeric actin
      organization. cas-1-mutant embryos and worms have aggregates of actin in muscle
      cells, and UNC-60B is mislocalized to the aggregates. These results provide
      genetic and biochemical evidence that cyclase-associated protein is a critical
      regulator of sarcomeric actin organization in striated muscle.

PMID- 22623723
TI  - Opposing microtubule motors drive robust nuclear dynamics in developing muscle
      cells.
AB  - Dynamic interactions with the cytoskeleton drive the movement and positioning of
      nuclei in many cell types. During muscle cell development, myoblasts fuse to form
      syncytial myofibers with nuclei positioned regularly along the length of the
      cell. Nuclear translocation in developing myotubes requires microtubules, but the
      mechanisms involved have not been elucidated. We find that as nuclei actively
      translocate through the cell, they rotate in three dimensions. The nuclear
      envelope, nucleoli and chromocenters within the nucleus rotate together as a
      unit. Both translocation and rotation require an intact microtubule cytoskeleton,
      which forms a dynamic bipolar network around nuclei. The plus- and minus-end
      directed microtubule motor proteins, kinesin-1 and dynein, localize to the
      nuclear envelope in myotubes. Kinesin-1 localization is mediated at least in part
      by interaction with klarsicht/ANC-1/Syne homology (KASH) proteins. Depletion of
      kinesin-1 abolishes nuclear rotation and significantly inhibits nuclear
      translocation, resulting in the abnormal aggregation of nuclei at the midline of
      the myotube. Dynein depletion also inhibits nuclear dynamics, but to a lesser
      extent, leading to altered spacing between adjacent nuclei. Thus, oppositely
      directed motors acting from the surface of the nucleus drive nuclear motility in
      myotubes. The variable dynamics observed for individual nuclei within a single
      myotube are likely to result from the stochastic activity of competing motors
      interacting with a complex bipolar microtubule cytoskeleton that is also
      continuously remodeled as the nuclei move. The three-dimensional rotation of
      myotube nuclei may facilitate their motility through the complex and crowded
      cellular environment of the developing muscle cell, allowing for proper
      myonuclear positioning.

PMID- 22623724
TI  - An orphan kinesin in trypanosomes cooperates with a kinetoplastid-specific
      kinesin to maintain cell morphology by regulating subpellicular microtubules.
AB  - Microtubules are a vital part of the cytoskeleton of eukaryotic cells and are
      involved in various cellular processes. The cytoskeleton of Trypanosoma brucei is
      characterized by an array of subpellicular microtubules and is essential for
      maintenance of cell shape and polarity, but little is known about the regulation
      of the assembly and organization of the subpellicular microtubule corset. Here,
      we report that the orphan kinesin TbKIN-D regulates the organization of
      subpellicular microtubules and is required for maintaining cell morphology. TbKIN
      D possesses in vitro ATPase activity, associates with cytoskeletal microtubules
      and is distributed throughout the cytoskeleton at all cell cycle stages. RNAi of
      TbKIN-D disrupts the organization of the subpellicular microtubule corset and
      distorts cell morphology, resulting in round cells with an elongated posterior
      filled with newly assembled microtubules. Depletion of TbKIN-D also abolishes the
      segregation of organelles and cytoskeletal structures, suggesting that cellular
      morphogenesis is essential for proper organelle segregation. Moreover, TbKIN-D
      deficiency impairs the attachment of the new flagellum without compromising the
      formation of the flagellum attachment zone. Finally, we identified TbKIN-C, a
      kinetoplastid-specific kinesin known to regulate subpellicular microtubules and
      cell morphogenesis in T. brucei, as a partner of TbKIN-D. Further, we demonstrate
      that interaction between TbKIN-C and TbKIN-D requires the coiled-coil motifs in
      the C-termini of both proteins. Altogether, our results suggest that TbKIN-D
      cooperates with TbKIN-C to maintain cell morphology by regulating the
      organization of the subpellicular microtubule corset.

PMID- 22623725
TI  - MLL1, a H3K4 methyltransferase, regulates the TNFalpha-stimulated activation of
      genes downstream of NF-kappaB.
AB  - Genes of the mixed lineage leukemia (MLL) family regulate transcription by
      methylating histone H3K4. Six members of the MLL family exist in humans,
      including SETD1A, SETD1B and MLL1-MLL4. Each of them plays non-redundant roles in
      development and disease genesis. MLL1 regulates the cell cycle and the
      oscillation of circadian gene expression. Its fusion proteins are involved in
      leukemogenesis. Here, we studied the role of MLL1 in innate immunity and found it
      selectively regulates the activation of genes downstream of NF-kappaB mediated by
      tumor necrosis factor (TNFalpha) and lipopolysaccharide (LPS). Real-time PCR and
      genome-wide gene expression profile analysis proved that the deficiency of MLL1
      reduced the expression of a group of genes downstream of nuclear factor kappaB
      (NF-kappaB). However, the activation of NF-kappaB itself was not affected. The
      MLL1 complex is found both in the nucleus and cytoplasm and is associated with NF
      kappaB. CHIP assays proved that the translocation of MLL1 to chromatin was
      dependent on NF-kappaB. Our results suggest that MLL1 is recruited to its target
      genes by activated NF-kappaB and regulates their transcription.

PMID- 22623726
TI  - Smad ubiquitination regulatory factor-2 controls gap junction intercellular
      communication by modulating endocytosis and degradation of connexin43.
AB  - Gap junctions consist of arrays of intercellular channels that enable adjacent
      cells to communicate both electrically and metabolically. Gap junction channels
      are made of a family of integral membrane proteins called connexins, of which the
      best-studied member is connexin43. Gap junctions are dynamic plasma membrane
      domains, and connexin43 has a high turnover rate in most tissue types. However,
      the mechanisms involved in the regulation of connexin43 endocytosis and transport
      to lysosomes are still poorly understood. Here, we demonstrate by live-cell
      imaging analysis that treatment of cells with 12-O-tetradecanoylphorbol 13
      acetate (TPA) induces endocytosis of subdomains of connexin43 gap junctions. The
      internalized, connexin43-enriched vesicles were found to fuse with early
      endosomes, which was followed by transport of connexin43 to the lumen of early
      endosomes. The HECT E3 ubiquitin ligase smad ubiquitination regulatory factor-2
      (Smurf2) was found to be recruited to connexin43 gap junctions in response to TPA
      treatment. Depletion of Smurf2 by small interfering RNA resulted in enhanced
      levels of connexin43 gap junctions between adjacent cells and increased gap
      junction intercellular communication. Smurf2 depletion also counteracted the TPA
      induced endocytosis and degradation of connexin43. Collectively, these data
      identify Smurf2 as a novel regulator of connexin43 gap junctions.

PMID- 22623727
TI  - Cofilin nuclear-cytoplasmic shuttling affects cofilin-actin rod formation during
      stress.
AB  - Cofilin protein is involved in regulating the actin cytoskeleton during typical
      steady state conditions, as well as during cell stress conditions where cofilin
      saturates F-actin, forming cofilin-actin rods. Cofilin can enter the nucleus
      through an active nuclear localization signal (NLS), accumulating in nuclear
      actin rods during stress. Here, we characterize the active nuclear export of
      cofilin through a leptomycin-B-sensitive, CRM1-dependent, nuclear export signal
      (NES). We also redefine the NLS of cofilin as a bipartite NLS, with an additional
      basic epitope required for nuclear localization. Using fluorescence lifetime
      imaging microscopy (FLIM) and Forster resonant energy transfer (FRET) between
      cofilin moieties and actin, as well as automated image analysis in live cells, we
      have defined subtle mutations in the cofilin NLS that allow cofilin to bind actin
      in vivo and affect cofilin dynamics during stress. We further define the
      requirement of cofilin-actin rod formation in a system of cell stress by temporal
      live-cell imaging. We propose that cofilin nuclear shuttling is critical for the
      cofilin-actin rod stress response with cofilin dynamically communicating between
      the nucleus and cytoplasm during cell stress.

PMID- 22623728
TI  - Scrib regulates HGF-mediated epithelial morphogenesis and is stabilized by Sgt1
      HSP90.
AB  - Scribble was originally identified as a Drosophila protein that regulates
      epithelial polarity and formation of the basolateral surface. The mammalian
      orthologue, Scrib, is evolutionarily conserved, but does not appear to be
      necessary for apical-basolateral epithelial polarity. Instead, it is implicated
      in the regulation of cell survival, protein trafficking, adhesion and migration.
      A key issue is to understand the molecular pathway by which Scrib participates in
      these processes. We have investigated Scrib using a three-dimensional epithelial
      cell culture system. We show a novel association between the leucine-rich repeat
      domain of Scrib and the co-chaperone Sgt1 and demonstrate that these proteins are
      necessary for epithelial morphogenesis and tubulogenesis following hepatocyte
      growth factor (HGF) stimulation. The molecular chaperone HSP90 is also required
      for Sgt1 association with Scrib, and both Sgt1 and HSP90 are needed to ensure
      proper Scrib protein levels. Furthermore, reduced Scrib stability, following
      inhibition of Sgt1-HSP90, lowers the cellular abundance of the Scrib-betaPix-PAK
      complex. Inhibition of any member of this complex, Scrib, betaPix or PAK, is
      sufficient to block HGF-mediated epithelial morphogenesis. The identification of
      Scrib as an Sgt1-HSP90 client protein required for three-dimensional cell
      migration suggests that chaperone-mediated regulation of polarity protein
      stability and homeostasis is an unappreciated mechanism underlying dynamic
      rearrangements during morphogenesis.

PMID- 22623729
TI  - The influence of parent preprocedural anxiety on child procedural pain: mediation
      by child procedural anxiety.
AB  - OBJECTIVE: Data suggest parents' preprocedural anxiety is related to children's
      acute procedural anxiety and pain. This study examined the temporal relations
      among these constructs to determine whether children's anxiety mediates the
      relation between parents' anticipatory anxiety and children's procedural pain.
      METHODS: A total of 90 preschoolers receiving immunizations, their parents, and
      the nurses rated children's procedural anxiety and pain. Parents provided ratings
      of their own preprocedural anxiety. RESULTS: Bootstrapping analyses revealed that
      children's procedural anxiety mediated the relation between parents'
      preprocedural anxiety and children's procedural pain according to parents' report
      and nurses' report but not children's self-report of anxiety and pain.
      CONCLUSIONS: Analyses suggest that children's procedural anxiety mediates the
      relation between parents' anticipatory anxiety and children's procedural pain.
      Thus, targeting parents' preprocedural anxiety might be beneficial to the parents
      as well as the children undergoing a distressing medical procedure.

PMID- 22623730
TI  - Integrative genomic analysis implicates gain of PIK3CA at 3q26 and MYC at 8q24 in
      chronic lymphocytic leukemia.
AB  - PURPOSE: The disease course of chronic lymphocytic leukemia (CLL) varies
      significantly within cytogenetic groups. We hypothesized that high-resolution
      genomic analysis of CLL would identify additional recurrent abnormalities
      associated with short time-to-first therapy (TTFT). EXPERIMENTAL DESIGN: We
      undertook high-resolution genomic analysis of 161 prospectively enrolled CLLs
      using Affymetrix 6.0 SNP arrays, and integrated analysis of this data set with
      gene expression profiles. RESULTS: Copy number analysis (CNA) of nonprogressive
      CLL reveals a stable genotype, with a median of only 1 somatic CNA per sample.
      Progressive CLL with 13q deletion was associated with additional somatic CNAs,
      and a greater number of CNAs was predictive of TTFT. We identified other
      recurrent CNAs associated with short TTFT: 8q24 amplification focused on the
      cancer susceptibility locus near MYC in 3.7%; 3q26 amplifications focused on
      PIK3CA in 5.6%; and 8p deletions in 5% of patients. Sequencing of MYC further
      identified somatic mutations in two CLLs. We determined which catalytic subunits
      of phosphoinositide 3-kinase (PI3K) were in active complex with the p85
      regulatory subunit and showed enrichment for the alpha subunit in three CLLs
      carrying PIK3CA amplification. CONCLUSIONS: Our findings implicate amplifications
      of 3q26 focused on PIK3CA and 8q24 focused on MYC in CLL.

PMID- 22623732
TI  - Serum insulin-like growth factor-1 levels predict outcomes of patients with
      advanced hepatocellular carcinoma receiving antiangiogenic therapy.
AB  - PURPOSE: Patients with liver cirrhosis or hepatocellular carcinoma (HCC) have
      decreased serum insulin-like growth factor (IGF)-1 levels. We evaluated whether
      IGF-1 levels were associated with the outcomes of patients with advanced HCC
      treated with systemic antiangiogenic therapy. EXPERIMENTAL DESIGN: The study was
      based on patients with advanced HCC who were enrolled in two clinical trials
      evaluating first-line combination antiangiogenic therapy. Serum samples were
      collected before treatment and four to six weeks after the start of treatment.
      The levels of IGF-1, IGF-2, and IGF-binding protein-3 (IGFBP3) were analyzed for
      their associations with treatment outcomes. RESULTS: A total of 83 patients were
      included in the study. Patients who had high (>=the median level) baseline IGF-1
      levels had significantly higher disease control rate (DCR) than patients who had
      low (<the median level) levels (71% vs. 39%, P = 0.003). The levels of
      posttreatment IGF-1, and pre- or posttreatment IGF-2 and IGFBP3 were not
      associated with DCR. Patients with high baseline IGF-1 levels, compared with
      patients with low levels, had significantly longer progression-free survival
      (PFS; median, 4.3 vs. 1.9 months, P = 0.014) and overall survival (OS; median,
      10.7 vs. 3.9 months, P = 0.009). The high baseline IGF-1 level remains an
      independent factor associated with favorable PFS and OS in multivariate analysis.
      CONCLUSIONS: High pretreatment IGF-1 levels were associated with better DCR, PFS,
      and OS of patients who received antiangiogenic therapy for advanced HCC. This
      finding warrants validation in large studies.

PMID- 22623733
TI  - Risk and return for the clinician-investigator.
AB  - In this case study, an early-career clinician-investigator discusses impending
      and future career issues in an interview with an established translational
      scientist, who then shares ideas about pursuing clinically informed research
      questions.

PMID- 22623731
TI  - Elevation of c-FLIP in castrate-resistant prostate cancer antagonizes therapeutic
      response to androgen receptor-targeted therapy.
AB  - PURPOSE: To characterize the importance of cellular Fas-associated death domain
      (FADD)-like interleukin 1beta-converting enzyme (FLICE) inhibitory protein (c
      FLIP), a key regulator of caspase-8 (FLICE)-promoted apoptosis, in modulating the
      response of prostate cancer cells to androgen receptor (AR)-targeted therapy.
      EXPERIMENTAL DESIGN: c-FLIP expression was characterized by immunohistochemical
      analysis of prostatectomy tissue. The functional importance of c-FLIP to survival
      and modulating response to bicalutamide was studied by molecular and
      pharmacologic interventions. RESULTS: c-FLIP expression was increased in high
      grade prostatic intraepithelial neoplasia and prostate cancer tissue relative to
      normal prostate epithelium (P < 0.001). Maximal c-FLIP expression was detected in
      castrate-resistant prostate cancer (CRPC; P < 0.001). In vitro, silencing of c
      FLIP induced spontaneous apoptosis and increased 22Rv1 and LNCaP cell sensitivity
      to bicalutamide, determined by flow cytometry, PARP cleavage, and caspase
      activity assays. The histone deacetylase inhibitors (HDACi), droxinostat and
      SAHA, also downregulated c-FLIP expression, induced caspase-8- and caspase-3/7
      mediated apoptosis, and increased apoptosis in bicalutamide-treated cells.
      Conversely, the elevated expression of c-FLIP detected in the CRPC cell line VCaP
      underpinned their insensitivity to bicalutamide and SAHA in vitro. However,
      knockdown of c-FLIP induced spontaneous apoptosis in VCaP cells, indicating its
      relevance to cell survival and therapeutic resistance. CONCLUSION: c-FLIP reduces
      the efficacy of AR-targeted therapy and maintains the viability of prostate
      cancer cells. A combination of HDACi with androgen deprivation therapy may be
      effective in early-stage disease, using c-FLIP expression as a predictive
      biomarker of sensitivity. Direct targeting of c-FLIP, however, may be relevant to
      enhance the response of existing and novel therapeutics in CRPC.

PMID- 22623734
TI  - Clinician-investigators as translational bioscientists: shaping a seamless
      identity.
AB  - Established biomedical scientists counsel early-career clinician-investigators
      and translational bioscientists on mechanisms for molding successful research
      careers that advance clinical medicine.

PMID- 22623735
TI  - TB and HIV: deadly liaison or manageable threat?
AB  - Researchers create a dynamic model that could resolve conflicting findings on the
      effects of HIV infection on drug-resistant tuberculosis.

PMID- 22623736
TI  - Comment on "the predictive capacity of personal genome sequencing".

PMID- 22623737
TI  - Comment on "the predictive capacity of personal genome sequencing".

PMID- 22623738
TI  - Comment on "the predictive capacity of personal genome sequencing".

PMID- 22623740
TI  - Effective adjunctive therapy by an innate defense regulatory peptide in a
      preclinical model of severe malaria.
AB  - Case fatality rates for severe malaria remain high even in the best clinical
      settings because antimalarial drugs act against the parasite without alleviating
      life-threatening inflammation. We assessed the potential for host-directed
      therapy of severe malaria of a new class of anti-inflammatory drugs, the innate
      defense regulator (IDR) peptides, based on host defense peptides. The Plasmodium
      berghei ANKA model of experimental cerebral malaria was adapted to use as a
      preclinical screen by combining late-stage intervention in established infections
      with advanced bioinformatic analysis of early transcriptional changes in co
      regulated gene sets. Coadministration of IDR-1018 with standard first-line
      antimalarials increased survival of infected mice while down-regulating key
      inflammatory networks associated with fatality. Thus, IDR peptides provided host
      directed adjunctive therapy for severe disease in combination with antimalarial
      treatment.

PMID- 22623741
TI  - Adenosine A2A receptor activation prevents wear particle-induced osteolysis.
AB  - Prosthesis loosening, associated with wear particle-induced inflammation and
      osteoclast-mediated bone destruction, is a common cause for joint implant
      failure, leading to revision surgery. Adenosine A(2A) receptors (A(2A)Rs) mediate
      potent anti-inflammatory effects in many tissues and prevent osteoclast
      differentiation. We tested the hypothesis that an A(2A)R agonist could reduce
      osteoclast-mediated bone resorption in a murine calvaria model of wear particle
      induced bone resorption. C57BL/6 and A(2A)R knockout (A(2A)R KO) mice received
      ultrahigh-molecular weight polyethylene particles and were treated daily with
      either saline or the A(2A)R agonist CGS21680. After 2 weeks, micro-computed
      tomography of calvaria demonstrated that CGS21680 reduced particle-induced bone
      pitting and porosity in a dose-dependent manner, increasing cortical bone and
      bone volume compared to control mice. Histological examination demonstrated
      diminished inflammation after treatment with CGS21680. In A(2A)R KO mice,
      CGS21680 did not affect osteoclast-mediated bone resorption or inflammation.
      Levels of bone resorption markers receptor activator of nuclear factor kappaB
      (RANK), RANK ligand, cathepsin K, CD163, and osteopontin were reduced after
      CGS21680 treatment, together with a reduction in osteoclasts. Secretion of
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha was significantly
      decreased, whereas IL-10 was markedly increased in bone by CGS21680. These
      results in mice suggest that site-specific delivery of an adenosine A(2A)R
      agonist could enhance implant survival, delaying or eliminating the need for
      revision arthroplastic surgery.

PMID- 22623742
TI  - PTH/PTHrP and vitamin D control antimicrobial peptide expression and
      susceptibility to bacterial skin infection.
AB  - The production of antimicrobial peptides is essential for protection against a
      wide variety of microbial pathogens and plays an important role in the
      pathogenesis of several diseases. The mechanisms responsible for expression of
      antimicrobial peptides are incompletely understood, but a role for vitamin D as a
      transcriptional inducer of the antimicrobial peptide cathelicidin has been
      proposed. We show that 1,25-dihydroxyvitamin D(3) (1,25-D3) acts together with
      parathyroid hormone (PTH), or the shared amino-terminal domain of PTH-related
      peptide (PTHrP), to synergistically increase cathelicidin and immune defense.
      Administration of PTH to mouse skin decreased susceptibility to skin infection by
      group A Streptococcus. Mice on dietary vitamin D(3) restriction that responded
      with an elevation in PTH have an increased risk of infection if they lack 1,25
      D3. These results identify PTH/PTHrP as a variable that serves to compensate for
      inadequate vitamin D during activation of antimicrobial peptide production.

PMID- 22623744
TI  - Homocysteine and cardiovascular risk: the perils of reductionism in a complex
      system.

PMID- 22623745
TI  - Rapid ultraperformance liquid chromatography-tandem mass spectrometry assay for a
      characteristic glycogen-derived tetrasaccharide in Pompe disease and other
      glycogen storage diseases.
AB  - BACKGROUND: Urinary excretion of the tetrasaccharide 6-alpha-D-glucopyranosyl
      maltotriose (Glc4) is increased in various clinical conditions associated with
      increased turnover or storage of glycogen, making Glc4 a potential biomarker for
      glycogen storage diseases (GSD). We developed an ultraperformance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) assay to detect Glc4 in
      urine without interference of the Glc4 isomer maltotetraose (M4). METHODS: Urine
      samples, diluted in 0.1% ammonium hydroxide containing the internal standard
      acarbose, were filtered, and the filtrate was analyzed by UPLC-MS/MS. RESULTS: We
      separated and quantified acarbose, M4, and Glc4 using the ion pairs m/z 644/161,
      665/161, and 665/179, respectively. Response of Glc4 was linear up to 1500
      MUmol/L and the limit of quantification was 2.8 MUmol/L. Intra- and interassay
      CVs were 18.0% and 18.4% (10 MUmol/L Glc4), and 10.5% and 16.2% (200 MUmol/L
      Glc4). Glc4 in control individuals (n = 116) decreased with increasing age from a
      mean value of 8.9 mmol/mol to 1.0 mmol/mol creatinine. M4 was present in 5% of
      urine samples. Mean Glc4 concentrations per age group in untreated patients with
      Pompe disease (GSD type II) (n = 66) were significantly higher, ranging from 39.4
      to 10.3 mmol/mol creatinine (P < 0.001-0.005). The diagnostic sensitivity of Glc4
      for GSD-II was 98.5% and the diagnostic specificity 92%. Urine Glc4 was also
      increased in GSD-III (8 of 9), GSD-IV (2 of 3) and GSD-IX (6 of 10) patients.
      CONCLUSIONS: The UPLC-MS/MS assay of Glc4 in urine was discriminative between
      Glc4 and M4 and confirmed the diagnosis in >98% of GSD-II cases.

PMID- 22623743
TI  - Modeling the dynamic relationship between HIV and the risk of drug-resistant
      tuberculosis.
AB  - The emergence of highly drug-resistant tuberculosis (TB) and interactions between
      TB and HIV epidemics pose serious challenges for TB control. Previous researchers
      have presented several hypotheses for why HIV-coinfected TB patients may suffer
      an increased risk of drug-resistant TB (DRTB) compared to other TB patients.
      Although some studies have found a positive association between an individual's
      HIV status and his or her subsequent risk of multidrug-resistant TB (MDRTB), the
      observed individual-level relationship between HIV and DRTB varies substantially
      among settings. Here, we develop a modeling framework to explore the effect of
      HIV on the dynamics of DRTB. The model captures the acquisition of resistance to
      important classes of TB drugs, imposes fitness costs associated with resistance
      conferring mutations, and allows for subsequent restoration of fitness because of
      compensatory mutations. Despite uncertainty in several key parameters, we
      demonstrate epidemic behavior that is robust over a range of assumptions. Whereas
      HIV facilitates the emergence of MDRTB within a community over several decades,
      HIV-seropositive individuals presenting with TB may, counterintuitively, be at
      lower risk of drug-resistant TB at early stages of the co-epidemic. This
      situation arises because many individuals with incident HIV infection will
      already harbor latent Mycobacterium tuberculosis infection acquired at an earlier
      time when drug resistance was less prevalent. We find that the rise of HIV can
      increase the prevalence of MDRTB within populations even as it lowers the average
      fitness of circulating MDRTB strains compared to similar populations unaffected
      by HIV. Preferential social mixing among individuals with similar HIV status and
      lower average CD4 counts among HIV-seropositive individuals further increase the
      expected burden of MDRTB. This model suggests that the individual-level
      association between HIV and drug-resistant forms of TB is dynamic, and therefore,
      cross-sectional studies that do not report a positive individual-level
      association will not provide assurance that HIV does not exacerbate the burden of
      resistant TB in the community.

PMID- 22623746
TI  - Altering the landscape for women in clinical chemistry: perspectives from
      multigenerational leaders.

PMID- 22623747
TI  - Maternal vitamin D status in pregnancy is associated with adiposity in the
      offspring: findings from the Southampton Women's Survey.
AB  - BACKGROUND: Low vitamin D status has been linked to adiposity, but little is
      known of the effects of low status in pregnancy on offspring body composition.
      OBJECTIVE: The objective was to determine how maternal vitamin D status relates
      to lean and fat mass of the offspring. DESIGN: The offspring of 977 pregnant
      women, who had serum 25-hydroxyvitamin D [25(OH)D] measured at 34 wk gestation,
      were followed up within 3 wk of birth and at 4 and 6 y of age for dual-energy X
      ray absorptiometry assessment of lean and fat mass. RESULTS: The median maternal
      serum 25(OH)D concentration was 62 nmol/L (IQR: 43-89 nmol/L); 35% of the women
      studied had values <50 nmol/L. Lower vitamin D status was associated with lower
      fat mass in the offspring at birth but with greater fat mass at ages 4 and 6 y.
      It was not associated with lean mass at any of the ages studied. The opposing
      associations seen between maternal 25(OH)D (SDs) and fat mass (SDs) in the
      offspring at birth and at age 6 y were robust to adjustment for a range of
      confounding factors, including maternal BMI and weight gain in pregnancy [beta
      (95% CI): 0.08 (0.02, 0.15) and -0.10 (-0.17, -0.02), respectively]. The key
      independent predictors of higher maternal vitamin D status were season of
      assessment and use of vitamin D supplements. CONCLUSIONS: Lower maternal vitamin
      D status may be linked to programmed differences in offspring fat mass. The
      findings require replication but add to a growing evidence base for a role of
      vitamin D in the origins of adiposity.

PMID- 22623748
TI  - Lower lifetime dietary fiber intake is associated with carotid artery stiffness:
      the Amsterdam Growth and Health Longitudinal Study.
AB  - BACKGROUND: Fiber intake is associated with lower cardiovascular disease risk.
      Whether arterial stiffness is influenced by lifetime fiber intake is not known.
      Any such association could explain, at least in part, the cardioprotective
      effects attributed to fiber intake. OBJECTIVE: The objective was to investigate
      whether a lower intake of fiber (and fiber-rich foods) throughout the course of
      young life (ie, from adolescence to adulthood) is associated with arterial
      stiffness in adulthood. DESIGN: This was a longitudinal cohort study among 373
      participants in whom dietary intake was assessed between the ages of 13 to 36 y
      (2-8 repeated measures, median of 5), and arterial stiffness estimates of 3 large
      arteries (ultrasonography) were ascertained at age 36 y. RESULTS: After
      adjustment for sex, height, total energy intake, and other lifestyle variables,
      subjects with stiffer carotid arteries consumed less fiber (in g/d) during the 24
      y study than did those with less stiff carotid arteries, as defined on the basis
      of the highest compared with the lowest sex-specific tertiles of the
      distensibility and compliance coefficients (reversed) and Young's elastic
      modulus: -1.9 (95% CI: -3.1, -0.7), -2.3 (-3.5, -1.1), and -1.3 (-2.5, -0.0),
      respectively. Furthermore, subjects with stiffer carotid arteries were
      characterized by a lower lifetime consumption of fruit, vegetables, and whole
      grains-deleterious associations that could be explained, to a great extent, by
      related low fiber intake. CONCLUSIONS: Lower lifetime intake of fiber during the
      course of young age is associated with carotid artery stiffness in adulthood.
      Promoting consumption of fiber-rich foods among the young may offer a means to
      prevent accelerated arterial stiffening in adulthood and related cardiovascular
      sequelae.

PMID- 22623750
TI  - Selenium and prostate cancer: the puzzle isn't finished yet.

PMID- 22623749
TI  - A cluster randomized controlled trial of a telephone-based parent intervention to
      increase preschoolers' fruit and vegetable consumption.
AB  - BACKGROUND: Inadequate fruit and vegetable consumption is associated with
      increased chronic disease risk and represents a considerable global health
      burden. Despite evidence that dietary habits track from early childhood, there
      are few published trials of interventions attempting to increase preschoolers'
      fruit and vegetable consumption. OBJECTIVE: The Healthy Habits trial aimed to
      assess the efficacy of a telephone-based intervention for parents to increase the
      fruit and vegetable consumption in their 3-5-y-old children. DESIGN: A cluster
      randomized controlled trial was conducted involving 394 parents of children aged
      3-5 y recruited through local preschools. Parents allocated to the intervention
      received printed resources plus four 30-min telephone calls targeting aspects of
      the home food environment associated with children's fruit and vegetable
      consumption. Parents allocated to the control group received generic printed
      nutrition information. Children's fruit and vegetable consumption was assessed by
      using the Fruit and Vegetable Subscale of the Children's Dietary Questionnaire,
      which was administered via telephone interview at baseline and 2 and 6 mo later.
      RESULTS: Analysis of all available data showed that children's fruit and
      vegetable scores were significantly higher in the intervention group than in the
      control group at 2 mo (P < 0.001) and at 6 mo (P = 0.021). Sensitivity analysis
      using baseline observation carried forward showed an intervention effect at 2 mo
      (P = 0.008) but not at 6 mo (P = 0.069). CONCLUSIONS: Telephone-delivered parent
      interventions may be an effective way of increasing children's fruit and
      vegetable consumption in the short term. Further investigation to determine
      whether the intervention effect is maintained in the longer term is recommended.

PMID- 22623751
TI  - Structure of the first sphingosine 1-phosphate receptor.
AB  - The sphingosine 1-phosphate receptor 1 (S1P1) and its ligand, sphingosine 1
      phosphate (S1P), have now emerged as critical regulators of lymphocyte
      trafficking, vascular development and integrity, and immunity. S1P1 is targeted
      by the phosphorylation product of fingolimod, which has been approved for the
      treatment of multiple sclerosis. The recent progress in the structural biology of
      heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors
      has now enabled the elucidation of the structure of S1P1. Analysis of the
      structure, along with structure activity and mutagenesis analysis, highlighted
      key interactions associated with the binding of S1P and agonists and suggested
      that the ligand may gain access to the binding pocket by lateral diffusion within
      the plasma membrane. The S1P1 crystal structure will be helpful for designing
      ligands that specifically target S1P1.

PMID- 22623752
TI  - Revisiting channel allostery: a coherent mechanism in IP3 and ryanodine
      receptors.
AB  - The inositol 1,4,5-trisphosphate (IP3) receptor is an IP3-gated calcium ion
      (Ca2+) channel that mediates intracellular IP3-Ca2+ signaling. A fundamental
      question--how IP3 gates the Ca2+ channel within the IP3 receptor--remains
      unanswered. A new crystal structure of the N-terminal region of the IP3 receptor
      reveals allosteric changes by ligand binding and its similarity to the
      corresponding region of ryanodine receptor. Docking of the crystal structures in
      the electron microscopy map and an IP3 receptor-ryanodine receptor chimera
      consistently supported a coherent gating mechanism in these receptors. An
      intriguing feature was the long distance between the IP3-binding sites and the
      Ca2+ channel, suggesting that long-range allosteric coupling occurs between these
      regions upon gating of the channel. These results help integrate previous
      knowledge on the IP3 and ryanodine receptors and also provide a new framework for
      understanding the gating mechanism.

PMID- 22623754
TI  - Reversible cerebral vasoconstriction syndrome induced by adrenaline.
AB  - INTRODUCTION: Reversible cerebral vasoconstriction syndrome (RCVS) is
      characterized by acute severe thunderclap headaches and evidence of multifocal,
      segmental, reversible vasoconstrictions of the cerebral arteries. Several
      precipitating factors have been identified and reported, including the use of
      recreational substances or sympathomimetic drugs and the postpartum state. CASE
      DESCRIPTION: Here we present the case of a woman who developed RCVS after the
      administration of adrenaline (epinephrine) in the setting of an anaphylactic
      reaction during antibiotic allergy testing. DISCUSSION: To our knowledge, this is
      the first reported case of RCVS following the administration of exogenous
      adrenaline. This case contributes to the understanding of the physiopathological
      mechanisms underlying reversible cerebral vasoconstriction.

PMID- 22623753
TI  - Interferon-beta therapy against EAE is effective only when development of the
      disease depends on the NLRP3 inflammasome.
AB  - Interferon-beta (IFN-beta) is widely used to treat multiple sclerosis (MS), and
      its efficacy was demonstrated in the setting of experimental autoimmune
      encephalomyelitis (EAE), an animal model of MS; however, IFN-beta is not
      effective in treating all cases of MS. Here, we demonstrate that signaling by
      IFNAR (the shared receptor for IFN-alpha and IFN-beta) on macrophages inhibits
      activation of Rac1 and the generation of reactive oxygen species (ROS) through
      suppressor of cytokine signaling 1 (SOCS1). The inhibition of Rac1 activation and
      ROS generation suppressed the activity of the Nod-like receptor (NLR) family,
      pyrin domain-containing 3 (NLRP3) inflammasome, which resulted in attenuated EAE
      pathogenicity. We further found that two subsets of EAE could be defined on the
      basis of their dependency on the NLRP3 inflammasome and that IFN-beta was not an
      effective therapy when EAE was induced in an NLRP3 inflammasome-independent
      fashion. Thus, our study demonstrates a previously uncharacterized signaling
      pathway that is involved in the suppression of EAE by IFN-beta and characterizes
      NLRP3-independent EAE, which cannot be treated with IFN-beta.

PMID- 22623755
TI  - Efficacy and safety of 121 injections of the greater occipital nerve in episodic
      and chronic cluster headache.
AB  - INTRODUCTION: Infiltration of the greater occipital nerve (GON) with local
      anaesthetics and corticosteroids is a treatment option for cluster headache.
      METHODS: We retrospectively analysed the efficacy and safety of 121 GON
      injections in 60 patients with episodic or chronic cluster headache over a period
      of 4 years. RESULTS: Almost 80% of the infiltrations were at least partially
      effective (reduction of attack frequency, duration or severity) and 45% resulted
      in a complete response (no further attacks). The effect was maintained for 3.5
      weeks on average in chronic cluster headache. In episodic cluster headache, the
      effect lasted for most of the bout. In 18 infiltrations, transient side effects
      were reported, such as local pain, steroid effects (facial oedema, sleeping
      disorders, acne), bradycardia or syncope. CONCLUSION: Our data show that GON
      infiltration is a valuable and safe option in the clinical setting to treat
      patients suffering from cluster headache, especially for the episodic form of the
      disorder.

PMID- 22623756
TI  - Visual aura of migraine versus visual occipital lobe seizures.

PMID- 22623757
TI  - Time course of the haemodynamic response to visual stimulation in migraine,
      measured using near-infrared spectroscopy.
AB  - BACKGROUND: In patients with migraine, an abnormally large haemodynamic response
      to epileptogenic visual stimulation has previously been observed, consistent with
      the hypothesis of a cortical hyperexcitability. Ophthalmic filters have been used
      in the treatment of migraine, and they reduce the haemodynamic response. METHODS:
      The present study used near-infrared spectroscopy (NIRS) to characterise the
      haemodynamic response to a range of visual stimuli in 20 patients with migraine
      (15 with aura and 5 without) and paired controls in order to assess the effect of
      ophthalmic treatment. In an initial study, the response to three stimuli
      (chequerboard, and two gratings of different spatial frequency) was measured. In
      a second study, using the mid-spatial frequency grating as stimulus, the response
      was compared when precision spectral filters (PSF), grey filters or filters of
      control colour were worn as ophthalmic lenses. RESULTS: In the first study the
      time course of the response differed between the groups. The difference was most
      distinct for the grating with mid-spatial frequency. In the second study the PSF
      broadened (normalised) the haemodynamic response in migraineurs relative to
      controls, consistent with fMRI BOLD findings and suggesting a physiological
      mechanism for their reported efficacy. In neither study were there differences in
      the amplitude of the response between migraine and control groups or indeed
      between filters. CONCLUSION: The time course of the functional response as
      measured by NIRS may be an effective tool to track therapy with PSF and explore
      the mechanisms of visual stress in migraine.

PMID- 22623758
TI  - Hypnic headache: response to lamotrigine in two cases.
AB  - BACKGROUND: Hypnic headache (HH) is a rare primary headache that occurs
      exclusively during sleep. Drug therapy of HH is often associated with side
      effects. In a few cases, antiepileptic drugs have been useful in preventing HH
      attacks. CASES: We describe two patients, a man aged 57 and a woman aged 63, both
      with a history of duodenal ulcer and both suffering from several months of
      frequent and moderate headaches (at least 15 days/month), which occurred only at
      night and resisted treatment. Physical examination and imaging were unremarkable.
      Sleep polysomnography was normal in the man. In both patients, the diagnosis of
      HH was made on the basis of the International Classification of Headache
      Disorders, 2nd edition criteria. Given the prior history of duodenal ulcer and
      the unavailability of some drugs in Morocco, we opted for the administration of
      moderate doses of lamotrigine. The outcome was favourable at one year follow-up
      and beyond. CONCLUSION: To our knowledge, the response to lamotrigine in HH cases
      has never been reported. Because of its safety profile and availability,
      lamotrigine can be an effective alternative treatment in HH.

PMID- 22623759
TI  - Airplane headache--an entity whose time has come to fly?

PMID- 22623760
TI  - Concurrent functional and structural cortical alterations in migraine.
AB  - AIM: Various animal and human studies have contributed to the idea of cortical
      structural-functional alterations in migraine. Defining concurrent cortical
      alterations may provide specific insights into the unfolding adaptive or
      maladaptive changes taking place in cortex in migraine. METHODS: From a group of
      60 episodic migraineurs, 20 were recruited to the study. Using high-resolution
      magnetic resonance imaging, structural and functional cortical measures were
      compared in migraineurs who experienced increased frequency of attacks (HF; 8-14
      days/month; n = 10), to those who experienced less frequent migraine attacks (LF;
      < 2 days/month; n = 10), and to healthy controls (HC; n = 20). RESULTS: Parallel
      structural and functional differences were found as follows: (i) HF patients
      showed higher thickness in the area representing the face in the post-central
      gyrus, which correlated with the observed stronger functional activation,
      suggesting adaptation to repeated sensory drive; (ii) smaller cortical volume was
      observed in the cingulate cortex that correlated with lower activation in the HF
      group; and (iii) similarly significant structural and functional differences (HF
      > LF) were observed in the insula that may reflect potential alteration in
      affective processing. CONCLUSION: These results suggest differential response
      patterns in the sensory vs. affective processing regions in the brain that may be
      an adaptive response to repeated migraine attacks.

PMID- 22623761
TI  - Characterization of headache after traumatic brain injury.
AB  - BACKGROUND: Headache is a common and persistent symptom following traumatic brain
      injury (TBI). Headaches following TBI are defined primarily by their temporal
      association to injury, but have no defining clinical features. To provide a
      framework for treatment, primary headache symptoms were used to characterize
      headache. METHODS: Three hundred and seventy-eight participants were
      prospectively enrolled during acute in-patient rehabilitation for TBI. Headaches
      were classified into migraine/probable migraine, tension-type, or cervicogenic
      headache at baseline and 3, 6, and 12 months following TBI. RESULTS: Migraine was
      the most frequent headache type occurring in up to 38% of participants who
      reported headaches. Probable migraine occurred in up to 25%, tension-type
      headache in up to 21%, then cervicogenic headache in up to 10%. Females were more
      likely to have endorsed pre-injury migraine than males, and had migraine or
      probable migraine at all time points after injury. Those classified with migraine
      were more likely to have frequent headaches. CONCLUSIONS: Our data show that most
      headache after TBI may be classified using primary headache criteria.
      Migraine/probable migraine described the majority of headache after TBI across
      one year post-injury. Using symptom-based criteria for headache following TBI can
      serve as a framework from which to provide evidence-based treatment for these
      frequent, severe, and persistent headaches.

PMID- 22623762
TI  - 'Ictal epileptic headache': recent concepts for new classifications criteria.

PMID- 22623763
TI  - Post-traumatic headaches: time for a revised classification?

PMID- 22623764
TI  - A short segment of the HIV-1 gp120 V1/V2 region is a major determinant of
      resistance to V1/V2 neutralizing antibodies.
AB  - Antibody PG9 is a prototypical member of a class of V1/V2-directed antibodies
      that effectively neutralizes diverse strains of HIV-1. We analyzed strain
      specific resistance to PG9 using sequence and structural information. For
      multiply resistant strains, mutations in a short segment of V1/V2 resulted in
      gain of sensitivity to PG9 and related V1/V2 neutralizing antibodies, suggesting
      both a common mechanism of HIV-1 resistance to and a common mode of recognition
      by this class of antibodies.

PMID- 22623765
TI  - Defective antiviral responses of induced pluripotent stem cells to baculoviral
      vector transduction.
AB  - Genetic engineering of induced pluripotent stem cells (iPSCs) is important for
      their clinical applications, and baculovirus (BV) holds promise as a gene
      delivery vector. To explore the feasibility of using BV for iPSCs transduction,
      in this study we first examined how iPSCs responded to BV. We determined that BV
      transduced iPSCs efficiently, without inducing appreciable negative effects on
      cell proliferation, apoptosis, pluripotency, and differentiation. BV transduction
      slightly perturbed the transcription of 12 genes involved in the Toll-like
      receptor (TLR) signaling pathway, but at the protein level BV elicited no well
      known cytokines (e.g., interleukin-6 [IL-6], tumor necrosis factor alpha [TNF
      alpha], and beta interferon [IFN-beta]) except for IP-10. Molecular analyses
      revealed that iPSCs expressed no TLR1, -6, -8, or -9 and expressed merely low
      levels of TLR2, -3, and -4. In spite of evident expression of such RNA/DNA
      sensors as RIG-I and AIM2, iPSCs barely expressed MDA5 and DAI (DNA-dependent
      activator of IFN regulatory factor [IRF]). Importantly, BV transduction of iPSCs
      stimulated none of the aforementioned sensors or their downstream signaling
      mediators (IRF3 and NF-kappaB). These data together confirmed that iPSCs
      responded poorly to BV due to the impaired sensing and signaling system, thereby
      justifying the transduction of iPSCs with the baculoviral vector.

PMID- 22623766
TI  - Orthobunyavirus entry into neurons and other mammalian cells occurs via clathrin
      mediated endocytosis and requires trafficking into early endosomes.
AB  - La Crosse virus (LACV) is a leading cause of pediatric encephalitis and aseptic
      meningitis in the midwestern and southern United States, where it is considered
      an emerging human pathogen. No specific therapies or vaccines are available for
      LACV or any other orthobunyaviruses. Inhibition of LACV entry into cells is a
      potential target for therapeutic intervention, but this approach is limited by
      our current knowledge of the entry process. Here, we determined that clathrin
      mediated endocytosis is the primary mechanism of orthobunyavirus entry and
      identified key cellular factors in this process. First, we demonstrated that LACV
      colocalized with clathrin shortly after infection in HeLa cells; we then
      confirmed the functional requirement of dynamin- and clathrin-mediated
      endocytosis for orthobunyavirus entry using several independent assays and,
      importantly, extended these findings to primary neuronal cultures. We also
      determined that macropinocytosis and caveolar endocytosis, both established
      routes of virus entry, are not critical for cellular entry of LACV. Moreover, we
      demonstrated that LACV infection is dependent on Rab5, which plays an important
      regulatory role in early endosomes, but not on Rab7, which is associated with
      late endosomes. These findings provide the first description of bunyavirus entry
      into cells of the central nervous system, where infection can cause severe
      neurological disease, and will aid in the design and development of antivirals
      and therapeutics that may be useful in the treatment of LACV and, more broadly,
      arboviral infections of the central nervous system.

PMID- 22623767
TI  - Epstein-Barr virus protein kinase BGLF4 targets the nucleus through interaction
      with nucleoporins.
AB  - BGLF4 of Epstein-Barr virus (EBV) encodes a serine/threonine protein kinase that
      phosphorylates multiple viral and cellular substrates to optimize the cellular
      environment for viral DNA replication and the nuclear egress of viral
      nucleocapsids. BGLF4 is expressed predominantly in the nucleus at early and late
      stages of virus replication, while a small portion of BGLF4 is distributed in the
      cytoplasm at the late stage of virus replication and packaged into the virion.
      Here, we analyzed systematically the functional domains crucial for nuclear
      localization of BGLF4 and found that both the N and C termini play important
      modulating roles. Analysis of amino acid substitution mutants revealed that the C
      terminus of BGLF4 does not contain a conventional nuclear localization signal
      (NLS). Additionally, deletion of the C-terminal putative helical regions at amino
      acids 386 to 393 and 410 to 419 diminished the nuclear translocation of BGLF4,
      indicating that the secondary structure of the C terminus is important for the
      localization of BGLF4. The green fluorescent protein-fused wild-type or C
      terminal helical regions of BGLF4 associate with phenylalanine/glycine repeat
      containing nucleoporins (Nups) in nuclear envelope fractionation. Both
      coimmunoprecipitation and in vitro pull-down assays further demonstrated that
      BGLF4 binds to Nup62 and Nup153. Remarkably, nuclear import assay with
      permeabilized HeLa cells demonstrated that BGLF4 translocated into nucleus
      independent of cytosolic factors. Data presented here suggest that BGLF4 employs
      a novel mechanism through direct interactions with nucleoporins for its nuclear
      targeting.

PMID- 22623768
TI  - Structure-based mutational analysis of the highly conserved domain IV of
      glycoprotein H of pseudorabies virus.
AB  - Glycoprotein H (gH) is an envelope protein conserved in the Herpesviridae.
      Together with glycoprotein B (gB), the heterodimeric complex of gH and
      glycoprotein L (gL) mediates penetration and direct viral cell-to-cell spread. In
      herpes simplex and pseudorabies virus (PrV), coexpression of gH/gL, gB, and gD
      induces membrane fusion to form polykaryocytes. The recently determined crystal
      structure of a core fragment of PrV gH revealed marked structural similarity to
      other gH proteins (M. Backovic et al., Proc. Natl. Acad. Sci. U. S. A. 107:22635
      22640, 2010). Within the membrane-proximal part (domain IV), a conserved
      negatively charged surface loop (flap) is flanked by intramolecular disulfide
      bonds. Together with an N-linked carbohydrate moiety, this flap covers an
      underlying patch of hydrophobic residues. To investigate the functional relevance
      of these structures, nonconservative amino acid substitutions were introduced by
      site-directed mutagenesis. The mutated proteins were tested for correct
      expression, fusion activity, and functional complementation of gH-deleted PrV.
      Several single amino acid changes within the flap and the hydrophobic patch were
      tolerated, and deletion of the glycosylation site had only minor effects.
      However, multiple alanine substitutions within the flap or the hydrophobic patch
      led to significant defects. gH function was also severely affected by disruption
      of the disulfide bond at the C terminus of the flap and after introduction of
      cysteine pairs designed to bridge the central part of the flap with the
      hydrophobic patch. Interestingly, all mutated gH proteins were able to complement
      gH-deleted PrV, but fusion-deficient gH mutants resulted in a pronounced delay in
      virus entry.

PMID- 22623769
TI  - Shutoff of BZLF1 gene expression is necessary for immortalization of primary B
      cells by Epstein-Barr virus.
AB  - The BZLF1 gene controls the switch between latent and lytic infection by Epstein
      Barr virus (EBV). We previously reported that both the ZV and ZIIR elements
      within the BZLF1 promoter, Zp, are potent transcription silencers within the
      context of an intact EBV genome. We report here identification of another
      sequence element, ZV', which synergized with ZV in repressing Zp via binding ZEB1
      or ZEB2. We then determined the phenotype of a variant of EBV strain B95.8 in
      which the ZV, ZV', and ZIIR elements were concurrently mutated. HEK293 cell lines
      infected with this triple mutant (tmt) virus spontaneously synthesized 6- to 10
      fold more viral BZLF1, BRLF1, BMRF1, and BLLF1 RNAs, 3- to 6-fold more viral Zta,
      Rta, and EAD proteins, 3- to 5-fold more viral DNA, and 7- to 9-fold more
      infectious virus than did 293 cell lines latently infected with either the ZV ZV'
      double mutant (dmt) or ZIIR mutant (mt) virus. While ZV ZV' ZIIR tmt EBV
      efficiently infected human primary blood B cells in vitro, it was highly
      defective in immortalizing them. Instead of the nearly complete silencing of
      BZLF1 gene expression that occurs within 4 days after primary infection with wild
      type EBV, the ZV ZV' ZIIR tmt-infected cells continued to synthesize BZLF1 RNA,
      with 90% of them dying within 9 days postinfection. BL41 cells infected with this
      "superlytic" virus also exhibited increased synthesis of BZLF1 and BMRF1 RNAs.
      Thus, we conclude that the ZV, ZV', and ZIIR silencing elements act
      synergistically to repress transcription from Zp, thereby tightly controlling
      BZLF1 gene expression, which is crucial for establishing and maintaining EBV
      latency.

PMID- 22623770
TI  - Activation of innate immune responses in the central nervous system during
      reovirus myelitis.
AB  - Reovirus infection of the murine spinal cord (SC) was used as a model system to
      investigate innate immune responses during viral myelitis, including the
      activation of glia (microglia and astrocytes) and interferon (IFN) signaling and
      increased expression of inflammatory mediators. Reovirus myelitis was associated
      with the pronounced activation of SC glia, as evidenced by characteristic changes
      in cellular morphology and increased expression of astrocyte and microglia
      specific proteins. Expression of inflammatory mediators known to be released by
      activated glia, including interleukin-1beta (IL-1beta), tumor necrosis factor
      alpha (TNF-alpha), chemokine (C-C motif) ligand 5 (CCL 5), chemokine (C-X-C
      motif) ligand 10 (CXCL10), and gamma interferon (IFN-gamma), was also
      significantly upregulated in the SC of reovirus-infected animals compared to mock
      infected controls. Reovirus infection of the mouse SC was also associated with
      increased expression of genes involved in IFN signaling, including IFN-stimulated
      genes (ISG). Further, reovirus infection of mice deficient in the expression of
      the IFN-alpha/beta receptor (IFNAR(-/-)) resulted in accelerated mortality,
      demonstrating that IFN signaling is protective during reovirus myelitis.
      Experiments performed in ex vivo SC slice cultures (SCSC) confirmed that resident
      SC cells contribute to the production of at least some of these inflammatory
      mediators and ISG during reovirus infection. Microglia, but not astrocytes, were
      still activated, and glia-associated inflammatory mediators were still produced
      in reovirus-infected INFAR(-/-) mice, demonstrating that IFN signaling is not
      absolutely required for these neuroinflammatory responses. Our results suggest
      that activated glia and inflammatory mediators contribute to a local
      microenvironment that is deleterious to neuronal survival.

PMID- 22623771
TI  - B-lymphocyte dysfunction in chronic HIV-1 infection does not prevent cross-clade
      neutralization breadth.
AB  - Aberrant expression of regulatory receptors programmed death-1 (PD-1) and B- and
      T-lymphocyte attenuator (BTLA) is linked with dysregulation and exhaustion of T
      lymphocytes during chronic human immunodeficiency virus type 1 (HIV-1) infection;
      however, less is known about whether a similar process impacts B-lymphocyte
      function during HIV-1 infection. We reasoned that disruption of the peripheral B
      cell compartment might be associated with decreased neutralizing antibody
      activity. Expression of markers that indicate dysregulation (BTLA and PD-1),
      immune activation (CD95), and proliferation (Ki-67) was evaluated in B cells from
      HIV-1-infected viremic and aviremic subjects and healthy subjects, in conjunction
      with immunoglobulin production and CD4 T cell count. Viral load and cross-clade
      neutralizing activity in plasma from viremic subjects were also assessed.
      Dysregulation of B lymphocytes was indicated by a marked disruption of peripheral
      B cell subsets, increased levels of PD-1 expression, and decreased levels of BTLA
      expression in viremic subjects compared to aviremic subjects and healthy
      controls. PD-1 and BTLA were correlated in a divergent fashion with immune
      activation, CD4 T cell count, and the total plasma IgG level, a functional
      correlate of B cell dysfunction. Within viremic subjects, the total IgG level
      correlated directly with cross-clade neutralizing activity in plasma. The
      findings demonstrate that even in chronically infected subjects in which B
      lymphocytes display multiple indications of dysfunction, antibodies that mediate
      cross-clade neutralization breadth continue to circulate in plasma.

PMID- 22623772
TI  - Epstein-Barr virus BPLF1 deubiquitinates PCNA and attenuates polymerase eta
      recruitment to DNA damage sites.
AB  - PCNA is monoubiquitinated in response to DNA damage and fork stalling and then
      initiates recruitment of specialized polymerases in the DNA damage tolerance
      pathway, translesion synthesis (TLS). Since PCNA is reported to associate with
      Epstein-Barr virus (EBV) DNA during its replication, we investigated whether the
      EBV deubiquitinating (DUB) enzyme encoded by BPLF1 targets ubiquitinated PCNA and
      disrupts TLS. An N-terminal BPLF1 fragment (a BPLF1 construct containing the
      first 246 amino acids [BPLF1 1-246]) associated with PCNA and attenuated its
      ubiquitination in response to fork-stalling agents UV and hydroxyurea in cultured
      cells. Moreover, monoubiquitinated PCNA was deubiquitinated after incubation with
      purified BPLF1 1-246 in vitro. BPLF1 1-246 dysregulated TLS by reducing
      recruitment of the specialized repair polymerase polymerase eta (Poleta) to the
      detergent-resistant chromatin compartment and virtually abolished localization of
      Poleta to nuclear repair foci, both hallmarks of TLS. Expression of BPLF1 1-246
      decreased viability of UV-treated cells and led to cell death, presumably through
      deubiquitination of PCNA and the inability to repair damaged DNA. Importantly,
      deubiquitination of PCNA could be detected endogenously in EBV-infected cells in
      comparison with samples expressing short hairpin RNA (shRNA) against BPLF1.
      Further, the specificity of the interaction between BPLF1 and PCNA was dependent
      upon a PCNA-interacting peptide (PIP) domain within the N-terminal region of
      BPLF1. Both DUB activity and PIP sequence are conserved in the members of the
      family Herpesviridae. Thus, deubiquitination of PCNA, normally deubiquitinated by
      cellular USP1, by the viral DUB can disrupt repair of DNA damage by compromising
      recruitment of TLS polymerase to stalled replication forks. PCNA is the first
      cellular target identified for BPLF1 and its deubiquitinating activity.

PMID- 22623773
TI  - Equine herpesvirus type 4 UL56 and UL49.5 proteins downregulate cell surface
      major histocompatibility complex class I expression independently of each other.
AB  - Major histocompatibility complex class I (MHC-I) molecules are critically
      important in the host defense against various pathogens through presentation of
      viral peptides to cytotoxic T lymphocytes (CTLs), a process resulting in the
      destruction of virus-infected cells. Herpesviruses interfere with CTL-mediated
      elimination of infected cells by various mechanisms, including inhibition of
      peptide transport and loading, perturbation of MHC-I trafficking, and rerouting
      and proteolysis of cell surface MHC-I. In this study, we show that equine
      herpesvirus type 4 (EHV-4) modulates MHC-I cell surface expression through two
      different mechanisms. First, EHV-4 can lead to a significant downregulation of
      MHC-I expression at the cell surface through the product of ORF1, a protein
      expressed with early kinetics from a gene that is homologous to herpes simplex
      virus 1 UL56. The EHV-4 UL56 protein reduces cell surface MHC-I as early as 4 h
      after infection. Second, EHV-4 can interfere with MHC-I antigen presentation,
      starting at 6 h after infection, by inhibition of the transporter associated with
      antigen processing (TAP) through its UL49.5 protein. Although pUL49.5 has no
      immediate effect on overall surface MHC-I levels in infected cells, it blocks the
      supply of antigenic peptides to the endoplasmic reticulum (ER) and transport of
      peptide-loaded MHC-I to the cell surface. Taken together, our results show that
      EHV-4 encodes at least two viral immune evasion proteins: pUL56 reduces MHC-I
      molecules on the cell surface at early times after infection, and pUL49.5
      interferes with MHC-I antigen presentation by blocking peptide transport in the
      ER.

PMID- 22623776
TI  - Serotype-specific neutralizing antibody epitopes of human adenovirus type 3 (HAdV
      3) and HAdV-7 reside in multiple hexon hypervariable regions.
AB  - Human adenovirus types 3 and 7 (HAdV-3 and HAdV-7) occur epidemically and
      contribute greatly to respiratory diseases, but there is no currently available
      licensed recombinant HAdV-3/HAdV-7 bivalent vaccine. Identification of serotype
      specific neutralizing antibody (NAb) epitopes for HAdV-3 and HAdV-7 will be
      beneficial for development of recombinant HAdV-3/HAdV-7 bivalent vaccines. In
      this study, four NAb epitopes within hexon hypervariable regions (HVRs) were
      predicted for HAdV-3 and HAdV-7, respectively, by using bioinformatics. Eight
      hexon chimeric adenovirus vectors with the alternation of only one predicted
      neutralizing epitope were constructed. Further in vitro and in vivo
      neutralization assays indicated that E2 (residing in HVR2) and E3 (residing in
      HVR5) are NAb epitopes for HAdV-7, and E3 plays a more important role in
      generating NAb responses. Cross-neutralization assays indicated that all four
      predicted epitopes, R1 to R4, are NAb epitopes for HAdV-3, and R1 (residing in
      HVR1) plays the most important role in generating NAb responses. Humoral immune
      responses elicited by the recombinant rAdH7R1 (containing the R1 epitope) were
      significantly and durably suppressed by HAdV-3-specific NAbs. Surprisingly, the
      rAdDeltaE3GFP-specific neutralizing epitope responses induced by rAdMHE3 (R3
      replaced by E3) and rAdMHE4 (R4 replaced by E4) were weaker than those of rAdMHE1
      (R1 replaced by E1) or rAdMHE2 (R2 relaced by E2) in vitro and in vivo.
      Furthermore, rAdMHE4 replicated more slowly in HEp-2 cells, and the final yield
      was about 10-fold lower than that of rAdDeltaE3GFP. The current findings
      contribute not only to the development of new adenovirus vaccine candidates, but
      also to the construction of new gene delivery vectors.

PMID- 22623775
TI  - Herpes simplex virus 2 infection impacts stress granule accumulation.
AB  - Interference with stress granule (SG) accumulation is gaining increased
      appreciation as a common strategy used by diverse viruses to facilitate their
      replication and to cope with translational arrest. Here, we examined the impact
      of infection by herpes simplex virus 2 (HSV-2) on SG accumulation by monitoring
      the localization of the SG components T cell internal antigen 1 (TIA-1), Ras
      GTPase-activating SH3-domain-binding protein (G3BP), and poly(A)-binding protein
      (PABP). Our results indicate that SGs do not accumulate in HSV-2-infected cells
      and that HSV-2 can interfere with arsenite-induced SG accumulation early after
      infection. Surprisingly, SG accumulation was inhibited despite increased
      phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha),
      implying that HSV-2 encodes previously unrecognized activities designed to
      maintain translation initiation downstream of eIF2alpha. SG accumulation was not
      inhibited in HSV-2-infected cells treated with pateamine A, an inducer that works
      independently of eIF2alpha phosphorylation. The SGs that accumulated following
      pateamine A treatment of infected cells contained G3BP and PABP but were largely
      devoid of TIA-1. We also identified novel nuclear structures containing TIA-1
      that form late in infection. These structures contain the RNA binding protein 68
      kDa Src-associated in mitosis (Sam68) and were noticeably absent in infected
      cells treated with inhibitors of viral DNA replication, suggesting that they
      arise as a result of late events in the virus replicative cycle.

PMID- 22623774
TI  - A novel bat herpesvirus encodes homologues of major histocompatibility complex
      classes I and II, C-type lectin, and a unique family of immune-related genes.
AB  - Herpesviruses or herpesviral sequences have been identified in various bat
      species. Here, we report the isolation, cell tropism, and complete genome
      sequence of a novel betaherpesvirus from the bat Miniopterus schreibersii (MsHV).
      In primary cell culture, MsHV causes cytopathic effects (CPE) and reaches peak
      virus production 2 weeks after infection. MsHV was found to infect and replicate
      less efficiently in a feline kidney cell, CRFK, and failed to replicate in 13
      other cell lines tested. Sequencing of the MsHV genome using the 454 system, with
      a 224-fold coverage, revealed a genome size of 222,870 bp. The genome was
      extensively analyzed in comparison to those of related viruses. Of the 190
      predicted open reading frames (ORFs), 40 were identified as herpesvirus core
      genes. Among 93 proteins with identifiable homologues in tree shrew herpesvirus
      (THV), human cytomegalovirus (HCMV), or rat cytomegalovirus (RCMV), most had
      highest sequence identities with THV counterparts. However, the MsHV genome
      organization is colinear with that of RCMV rather than that of THV. The following
      unique features were discovered in the MsHV genome. One predicted protein, B125,
      is similar to human herpesvirus 6 (HHV-6) U94, a homologue of the parvovirus Rep
      protein. For the unique ORFs, 7 are predicted to encode major histocompatibility
      complex (MHC)-related proteins, 2 to encode MHC class I homologues, and 3 to
      encode MHC class II homologues; 4 encode the homologues of C-type lectin- or
      natural killer cell lectin-like receptors;, and the products of a unique gene
      family, the b149 family, of 16 members, have no significant sequence identity
      with known proteins but exhibit immunoglobulin-like beta-sandwich domains
      revealed by three-dimensional (3D) structural prediction. To our knowledge, MsHV
      is the first virus genome known to encode MHC class II homologues.

PMID- 22623777
TI  - The A33-dependent incorporation of B5 into extracellular enveloped vaccinia
      virions is mediated through an interaction between their lumenal domains.
AB  - There are two mechanisms for the incorporation of B5 into the envelope of
      extracellular virions produced by orthopoxviruses, one that requires A33 and one
      that does not. We have hypothesized that the A33-dependent mechanism requires a
      direct interaction between A33 and B5. In this study, chimeric constructs of A33
      and B5/B5-green fluorescent protein (GFP) were used to show that the two proteins
      interact through their lumenal domains and that the coiled-coil domain of B5 is
      sufficient for an interaction with A33. Furthermore, our experiments reveal that
      a transmembrane domain, not necessarily its own, is requisite for the lumenal
      domain of B5 to interact with A33. In contrast, the lumenal domain of A33 is
      sufficient for interaction with B5. Furthermore, the lumenal domain of A33 is
      sufficient to restore the proper localization of B5-GFP in infected cells. Taken
      together, our results demonstrate that the lumenal domains of A33 and B5 interact
      and that the interaction is required for the incorporation of B5-GFP into
      extracellular virions, whereas the incorporation of A33 is independent of B5.
      These results suggest that viral protein incorporation into extracellular virions
      is an active process requiring specific protein-protein interactions.

PMID- 22623778
TI  - Human respiratory syncytial virus nucleoprotein and inclusion bodies antagonize
      the innate immune response mediated by MDA5 and MAVS.
AB  - Currently, the spatial distribution of human respiratory syncytial virus (hRSV)
      proteins and RNAs in infected cells is still under investigation, with many
      unanswered questions regarding the interaction of virus-induced structures and
      the innate immune system. Very few studies of hRSV have used subcellular imaging
      as a means to explore the changes in localization of retinoic-acid-inducible gene
      I (RIG-I)-like receptors or the mitochondrial antiviral signaling (MAVS) protein,
      in response to the infection and formation of viral structures. In this
      investigation, we found that both RIG-I and melanoma differentiation-associated
      gene 5 (MDA5) colocalized with viral genomic RNA and the nucleoprotein (N) as
      early as 6 h postinfection (hpi). By 12 hpi, MDA5 and MAVS were observed within
      large viral inclusion bodies (IB). We used a proximity ligation assay (PLA) and
      determined that the N protein was in close proximity to MDA5 and MAVS in IBs
      throughout the course of the infection. Similar results were found with the
      transient coexpression of N and the phosphoprotein (P). Additionally, we
      demonstrated that the localization of MDA5 and MAVS in IBs inhibited the
      expression of interferon beta mRNA 27-fold following Newcastle disease virus
      infection. From these data, we concluded that the N likely interacts with MDA5,
      is in close proximity to MAVS, and localizes these molecules within IBs in order
      to attenuate the interferon response. To our knowledge, this is the first report
      of a specific function for hRSV IBs and of the hRSV N protein as a modulator of
      the innate immune response.

PMID- 22623779
TI  - Progressive loss of memory T cell potential and commitment to exhaustion during
      chronic viral infection.
AB  - T cell exhaustion and loss of memory potential occur during many chronic viral
      infections and cancer. We investigated when during chronic viral infection virus
      specific CD8 T cells lose the potential to form memory. Virus-specific CD8 T
      cells from established chronic infection were unable to become memory CD8 T cells
      if removed from infection. However, at earlier stages of chronic infection, these
      virus-specific CD8 T cells retained the potential to partially or fully revert to
      a memory differentiation program after transfer to infection-free mice.
      Conversely, effector CD8 T cells primed during acute infection were not protected
      from exhaustion if transferred to a chronic infection. We also tested whether
      memory and exhausted CD8 T cells arose from different subpopulations of effector
      CD8 T cells and found that only the KLRG1(lo) memory precursor subset gave rise
      to exhausted CD8 T cells. Together, these studies demonstrate that CD8 T cell
      exhaustion is a progressive developmental process. Early during chronic
      infection, the fate of virus-specific CD8 T cells remains plastic, while later,
      exhausted CD8 T cells become fixed in their differentiation state. Moreover,
      exhausted CD8 T cells arise from the memory precursor and not the terminally
      differentiated subset of effector CD8 T cells. These studies have implications
      for our understanding of senescence versus exhaustion and for therapeutic
      interventions during chronic infection.

PMID- 22623780
TI  - An Epstein-Barr Virus (EBV) mutant with enhanced BZLF1 expression causes
      lymphomas with abortive lytic EBV infection in a humanized mouse model.
AB  - Immunosuppressed patients are at risk for developing Epstein-Barr Virus (EBV)
      positive lymphomas that express the major EBV oncoprotein, LMP1. Although
      increasing evidence suggests that a small number of lytically infected cells may
      promote EBV-positive lymphomas, the impact of enhanced lytic gene expression on
      the ability of EBV to induce lymphomas is unclear. Here we have used immune
      deficient mice, engrafted with human fetal hematopoietic stem cells and thymus
      and liver tissue, to compare lymphoma formation following infection with wild
      type (WT) EBV versus infection with a "superlytic" (SL) mutant with enhanced
      BZLF1 (Z) expression. The same proportions (2/6) of the WT and SL virus-infected
      animals developed B-cell lymphomas by day 60 postinfection; the remainder of the
      animals had persistent tumor-free viral latency. In contrast, all WT and SL virus
      infected animals treated with the OKT3 anti-CD3 antibody (which inhibits T-cell
      function) developed lymphomas by day 29. Lymphomas in OKT3-treated animals (in
      contrast to lymphomas in the untreated animals) contained many LMP1-expressing
      cells. The SL virus-infected lymphomas in both OKT3-treated and untreated animals
      contained many more Z-expressing cells (up to 30%) than the WT virus-infected
      lymphomas, but did not express late viral proteins and thus had an abortive lytic
      form of EBV infection. LMP1 and BMRF1 (an early lytic viral protein) were never
      coexpressed in the same cell, suggesting that LMP1 expression is incompatible
      with lytic viral reactivation. These results show that the SL mutant induces an
      "abortive" lytic infection in humanized mice that is compatible with continued
      cell growth and at least partially resistant to T-cell killing.

PMID- 22623781
TI  - Cellular GCN5 is a novel regulator of human adenovirus E1A-conserved region 3
      transactivation.
AB  - The largest isoform of adenovirus early region 1A (E1A) contains a unique region
      termed conserved region 3 (CR3). This region activates viral gene expression by
      recruiting cellular transcription machinery to the early viral promoters. Recent
      studies have suggested that there is an optimal level of E1A-dependent
      transactivation required by human adenovirus (hAd) during infection and that this
      may be achieved via functional cross talk between the N termini of E1A and CR3.
      The N terminus of E1A binds GCN5, a cellular lysine acetyltransferase (KAT). We
      have identified a second independent interaction of E1A with GCN5 that is
      mediated by CR3, which requires residues 178 to 188 in hAd5 E1A. GCN5 was
      recruited to the viral genome during infection in an E1A-dependent manner, and
      this required both GCN5 interaction sites on E1A. Ectopic expression of GCN5
      repressed transactivation by both E1A CR3 and full-length E1A. In contrast, RNA
      interference (RNAi) depletion of GCN5 or treatment with the KAT inhibitor
      cyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl]hydrazone (CPTH2) resulted in
      increased E1A CR3 transactivation. Moreover, activation of the adenovirus E4
      promoter by E1A was increased during infection of homozygous GCN5 KAT-defective
      (hat/hat) mouse embryonic fibroblasts (MEFs) compared to wild-type control MEFs.
      Enhanced histone H3 K9/K14 acetylation at the viral E4 promoter required the
      newly identified binding site for GCN5 within CR3 and correlated with repression
      and reduced occupancy by phosphorylated RNA polymerase II. Treatment with CPTH2
      during infection also reduced virus yield. These data identify GCN5 as a new
      negative regulator of transactivation by E1A and suggest that its KAT activity is
      required for optimal virus replication.

PMID- 22623782
TI  - Increased interaction between vaccinia virus proteins A33 and B5 is detrimental
      to infectious extracellular enveloped virion production.
AB  - Two mechanisms exist for the incorporation of B5 into extracellular virions, one
      of which is dependent on A33. In the companion to this paper (W. M. Chan and B.
      M. Ward, J. Virol. 86:8210-8220, 2012), we show that the lumenal domain of A33 is
      sufficient for interaction with the coiled-coil domain of B5 and capable of
      directing B5-green fluorescent protein (GFP) into extracellular virions. Here, we
      have created a panel of charge-to-alanine mutations in the lumenal domain of A33
      to map the B5 interaction site. While none of these mutations abolished the
      interaction with B5, a subset displayed an increased interaction with both B5 and
      B5-GFP. Both B5 and B5-GFP recombinant viruses expressing these mutant proteins
      in place of normal A33 had a small-plaque phenotype. The increased interaction of
      the mutant proteins was detected during infection, suggesting that normally the
      interaction is either weak or transient. In addition, the increased A33-B5
      interaction was detected on virions produced by recombinant viruses and
      correlated with reduced target cell binding. Taken together, these results show
      that both B5 and B5-GFP interact with A33 during infection and that the duration
      of this interaction needs to be regulated for the production of fully infectious
      extracellular virions.

PMID- 22623783
TI  - Membrane requirement for folding of the herpes simplex virus 1 gB cytodomain
      suggests a unique mechanism of fusion regulation.
AB  - Herpes simplex virus type 1 (HSV-1) enters cells by fusion of its envelope with a
      host cell membrane, which requires four viral glycoproteins and a cellular
      receptor. Viral fusion glycoprotein B (gB) mediates membrane fusion through the
      action of its ectodomain, while its cytoplasmic domain (cytodomain) regulates
      fusion from the opposite face of the membrane by an unknown mechanism. The gB
      cytodomain appears to restrict fusion, because point or truncation mutations
      within it increase the extent of fusion (syn mutations). Previously, we showed
      that the hyperfusion phenotype correlated with reduced membrane binding in gB syn
      truncation mutants and proposed that membrane binding was important in regulating
      fusion. Here, we extended our analysis to three syn point mutants: A855V, R858H,
      and A874P. These mutations produce local conformational changes, with some
      affecting membrane interaction, which suggests that while syn mutants may
      deregulate fusion by somewhat different mechanisms, maintaining the wild-type
      (WT) conformation is critical for fusion regulation. We further show that the
      presence of a membrane is necessary for the cytodomain to achieve its fully
      folded conformation and propose that the membrane-bound form of the cytodomain
      represents its native conformation. Taken together, our data suggest that the
      cytodomain of gB regulates fusion by a novel mechanism in which membrane
      interaction plays a key role.

PMID- 22623784
TI  - Switching on RNA silencing suppressor activity by restoring argonaute binding to
      a viral protein.
AB  - We found that Sweet potato feathery mottle virus (SPFMV) P1, a close homologue of
      Sweet potato mild mottle virus P1, did not have any silencing suppressor
      activity. Remodeling the Argonaute (AGO) binding domain of SPFMV P1 by the
      introduction of two additional WG/GW motifs converted it to a silencing
      suppressor with AGO binding capacity. To our knowledge, this is the first
      instance of the transformation of a viral protein of unknown function to a
      functional silencing suppressor.

PMID- 22623785
TI  - The fanconi anemia pathway limits human papillomavirus replication.
AB  - High-risk human papillomaviruses (HPVs) deregulate epidermal differentiation and
      cause anogenital and head and neck squamous cell carcinomas (SCCs). The E7 gene
      is considered the predominant viral oncogene and drives proliferation and genome
      instability. While the implementation of routine screens has greatly reduced the
      incidence of cervical cancers which are almost exclusively HPV positive, the
      proportion of HPV-positive head and neck SCCs is on the rise. High levels of HPV
      oncogene expression and genome load are linked to disease progression, but
      genetic risk factors that regulate oncogene abundance and/or genome amplification
      remain poorly understood. Fanconi anemia (FA) is a genome instability syndrome
      characterized at least in part by extreme susceptibility to SCCs. FA results from
      mutations in one of 15 genes in the FA pathway, whose protein products assemble
      in the nucleus and play important roles in DNA damage repair. We report here that
      loss of FA pathway components FANCA and FANCD2 stimulates E7 protein accumulation
      in human keratinocytes and causes increased epithelial proliferation and basal
      cell layer expansion in the HPV-positive epidermis. Additionally, FANCD2 loss
      stimulates HPV genome amplification in differentiating cells, demonstrating that
      the intact FA pathway functions to restrict the HPV life cycle. These findings
      raise the possibility that FA genes suppress HPV infection and disease and
      suggest possible mechanism(s) for reported associations of HPV with an FA cohort
      in Brazil and for allelic variation of FA genes with HPV persistence in the
      general population.

PMID- 22623786
TI  - Structural and biochemical characterization of the vaccinia virus envelope
      protein D8 and its recognition by the antibody LA5.
AB  - Smallpox vaccine is considered a gold standard of vaccines, as it is the only one
      that has led to the complete eradication of an infectious disease from the human
      population. B cell responses are critical for the protective immunity induced by
      the vaccine, yet their targeted epitopes recognized in humans remain poorly
      described. Here we describe the biochemical and structural characterization of
      one of the immunodominant vaccinia virus (VACV) antigens, D8, and its binding to
      the monoclonal antibody LA5, which is capable of neutralizing VACV in the
      presence of complement. The full-length D8 ectodomain was found to form a
      tetramer. We determined the crystal structure of the LA5 Fab-monomeric D8 complex
      at a resolution of 2.1 A, as well as the unliganded structures of D8 and LA5-Fab
      at resolutions of 1.42 A and 1.6 A, respectively. D8 features a carbonic
      anhydrase (CAH) fold that has evolved to bind to the glycosaminoglycan (GAG)
      chondroitin sulfate (CS) on host cells. The central positively charged crevice of
      D8 was predicted to be the CS binding site by automated docking experiments.
      Furthermore, sequence alignment of various poxvirus D8 orthologs revealed that
      this crevice is structurally conserved. The D8 epitope is formed by 23
      discontinuous residues that are spread across 80% of the D8 protein sequence.
      Interestingly, LA5 binds with a high-affinity lock-and-key mechanism above this
      crevice with an unusually large antibody-antigen interface, burying 2,434 A(2) of
      protein surface.

PMID- 22623787
TI  - Replication of minute virus of mice in murine cells is facilitated by virally
      induced depletion of p21.
AB  - The DNA damage response to infection with minute virus of mice (MVM) leads to
      activated p53; however, p21 levels are reduced via a proteasome-mediated
      mechanism. This loss was sustained, as virus replicated in infected cells held at
      the G(2)/M border. Addition of the cyclin-dependent kinase (CDK) inhibitor
      roscovitine after S-phase entry reduced MVM replication, suggesting that CDK
      activity was critical for continued viral replication and virus-induced reduction
      of p21 may thus be necessary to prevent inhibition of CDK.

PMID- 22623788
TI  - Arenavirus nucleoproteins prevent activation of nuclear factor kappa B.
AB  - Arenaviruses include several causative agents of hemorrhagic fever (HF) disease
      in humans that are associated with high morbidity and significant mortality.
      Morbidity and lethality associated with HF arenaviruses are believed to involve
      the dysregulation of the host innate immune and inflammatory responses that leads
      to impaired development of protective and efficient immunity. The molecular
      mechanisms underlying this dysregulation are not completely understood, but it is
      suggested that viral infection leads to disruption of early host defenses and
      contributes to arenavirus pathogenesis in humans. We demonstrate in the
      accompanying paper that the prototype member in the family, lymphocytic
      choriomeningitis virus (LCMV), disables the host innate defense by interfering
      with type I interferon (IFN-I) production through inhibition of the interferon
      regulatory factor 3 (IRF3) activation pathway and that the viral nucleoprotein
      (NP) alone is responsible for this inhibitory effect (C. Pythoud, W. W. Rodrigo,
      G. Pasqual, S. Rothenberger, L. Martinez-Sobrido, J. C. de la Torre, and S. Kunz,
      J. Virol. 86:7728-7738, 2012). In this report, we show that LCMV-NP, as well as
      NPs encoded by representative members of both Old World (OW) and New World (NW)
      arenaviruses, also inhibits the nuclear translocation and transcriptional
      activity of the nuclear factor kappa B (NF-kappaB). Similar to the situation
      previously reported for IRF3, Tacaribe virus NP (TCRV-NP) does not inhibit NF
      kappaB nuclear translocation and transcriptional activity to levels comparable to
      those seen with other members in the family. Altogether, our findings demonstrate
      that arenavirus infection inhibits NF-kappaB-dependent innate immune and
      inflammatory responses, possibly playing a key role in the pathogenesis and
      virulence of arenavirus.

PMID- 22623789
TI  - New PARP gene with an anti-alphavirus function.
AB  - Alphaviruses represent a highly important group of human and animal pathogens,
      which are transmitted by mosquito vectors between vertebrate hosts. The hallmark
      of alphavirus infection in vertebrates is the induction of a high-titer viremia,
      which is strongly dependent on the ability of the virus to interfere with host
      antiviral responses on both cellular and organismal levels. The identification of
      cellular factors, which are critical in orchestrating virus clearance without the
      development of cytopathic effect, may prove crucial in the design of new and
      highly effective antiviral treatments. To address this issue, we have developed a
      noncytopathic Venezuelan equine encephalitis virus (VEEV) mutant that can
      persistently replicate in cells defective in type I interferon (IFN) production
      or signaling but is cleared from IFN signaling-competent cells. Using this
      mutant, we analyzed (i) the spectrum of cellular genes activated by virus
      replication in the persistently infected cells and (ii) the spectrum of genes
      activated during noncytopathic virus clearance. By applying microarray-based
      technology and bioinformatic analysis, we identified a number of IFN-stimulated
      genes (ISGs) specifically activated during VEEV clearance. One of these gene
      products, the long isoform of PARP12 (PARP12L), demonstrated an inhibitory effect
      on the replication of VEEV, as well as other alphaviruses and several different
      types of other RNA viruses. Additionally, overexpression of two other members of
      the PARP gene superfamily was also shown to be capable of inhibiting VEEV
      replication.

PMID- 22623790
TI  - Metagenomic characterization of airborne viral DNA diversity in the near-surface
      atmosphere.
AB  - Airborne viruses are expected to be ubiquitous in the atmosphere but they still
      remain poorly understood. This study investigated the temporal and spatial
      dynamics of airborne viruses and their genotypic characteristics in air samples
      collected from three distinct land use types (a residential district [RD], a
      forest [FR], and an industrial complex [IC]) and from rainwater samples freshly
      precipitated at the RD site (RD-rain). Viral abundance exhibited a seasonal
      fluctuation in the range between 1.7 * 10(6) and 4.0 * 10(7) viruses m(-3), which
      increased from autumn to winter and decreased toward spring, but no significant
      spatial differences were observed. Temporal variations in viral abundance were
      inversely correlated with seasonal changes in temperature and absolute humidity.
      Metagenomic analysis of air viromes amplified by rolling-circle phi29 polymerase
      based random hexamer priming indicated the dominance of plant-associated single
      stranded DNA (ssDNA) geminivirus-related viruses, followed by animal-infecting
      circovirus-related sequences, with low numbers of nanoviruses and microphages
      related genomes. Particularly, the majority of the geminivirus-related viruses
      were closely related to ssDNA mycoviruses that infect plant-pathogenic fungi.
      Phylogenetic analysis based on the replication initiator protein sequence
      indicated that the airborne ssDNA viruses were distantly related to known ssDNA
      viruses, suggesting that a high diversity of viruses were newly discovered. This
      research is the first to report the seasonality of airborne viruses and their
      genetic diversity, which enhances our understanding of viral ecology in temperate
      regions.

PMID- 22623791
TI  - Herpes simplex virus 1 infection activates poly(ADP-ribose) polymerase and
      triggers the degradation of poly(ADP-ribose) glycohydrolase.
AB  - Herpes simplex virus 1 infection triggers multiple changes in the metabolism of
      host cells, including a dramatic decrease in the levels of NAD(+). In addition to
      its role as a cofactor in reduction-oxidation reactions, NAD(+) is required for
      certain posttranslational modifications. Members of the poly(ADP-ribose)
      polymerase (PARP) family of enzymes are major consumers of NAD(+), which they
      utilize to form poly(ADP-ribose) (PAR) chains on protein substrates in response
      to DNA damage. PAR chains can subsequently be removed by the enzyme poly(ADP
      ribose) glycohydrolase (PARG). We report here that the HSV-1 infection-induced
      drop in NAD(+) levels required viral DNA replication, was associated with an
      increase in protein poly(ADP-ribosyl)ation (PARylation), and was blocked by
      pharmacological inhibition of PARP-1/PARP-2 (PARP-1/2). Neither virus yield nor
      the cellular metabolic reprogramming observed during HSV-1 infection was altered
      by the rescue or further depletion of NAD(+) levels. Expression of the viral
      protein ICP0, which possesses E3 ubiquitin ligase activity, was both necessary
      and sufficient for the degradation of the 111-kDa PARG isoform. This work
      demonstrates that HSV-1 infection results in changes to NAD(+) metabolism by PARP
      1/2 and PARG, and as PAR chain accumulation can induce caspase-independent
      apoptosis, we speculate that the decrease in PARG levels enhances the auto
      PARylation-mediated inhibition of PARP, thereby avoiding premature death of the
      infected cell.

PMID- 22623792
TI  - Involvement of the chloroplastic isoform of tRNA ligase in the replication of
      viroids belonging to the family Avsunviroidae.
AB  - Avocado sunblotch viroid, peach latent mosaic viroid, chrysanthemum chlorotic
      mottle viroid, and eggplant latent viroid (ELVd), the four recognized members of
      the family Avsunviroidae, replicate through the symmetric pathway of an RNA-to
      RNA rolling-circle mechanism in chloroplasts of infected cells. Viroid oligomeric
      transcripts of both polarities contain embedded hammerhead ribozymes that, during
      replication, mediate their self-cleavage to monomeric-length RNAs with 5'
      hydroxyl and 2',3'-phosphodiester termini that are subsequently circularized. We
      report that a recombinant version of the chloroplastic isoform of the tRNA ligase
      from eggplant (Solanum melongena L.) efficiently catalyzes in vitro
      circularization of the plus [(+)] and minus [(-)] monomeric linear replication
      intermediates from the four Avsunviroidae. We also show that while this RNA
      ligase specifically recognizes the genuine monomeric linear (+) ELVd replication
      intermediate, it does not do so with five other monomeric linear (+) ELVd RNAs
      with their ends mapping at different sites along the molecule, despite containing
      the same 5'-hydroxyl and 2',3'-phosphodiester terminal groups. Moreover,
      experiments involving transient expression of a dimeric (+) ELVd transcript in
      Nicotiana benthamiana Domin plants preinoculated with a tobacco rattle virus
      derived vector to induce silencing of the plant endogenous tRNA ligase show a
      significant reduction of ELVd circularization. In contrast, circularization of a
      viroid replicating in the nucleus occurring through a different pathway is
      unaffected. Together, these results support the conclusion that the chloroplastic
      isoform of the plant tRNA ligase is the host enzyme mediating circularization of
      both (+) and (-) monomeric linear intermediates during replication of the viroids
      belonging to the family Avsunviroidae.

PMID- 22623793
TI  - Identification of novel host cell binding partners of Oas1b, the protein
      conferring resistance to flavivirus-induced disease in mice.
AB  - Oas1b was previously identified as the product of the Flv(r) allele that confers
      flavivirus-specific resistance to virus-induced disease in mice by an
      uncharacterized, RNase L-independent mechanism. To gain insights about the
      mechanism by which Oas1b specifically reduces the efficiency of flavivirus
      replication, cellular protein interaction partners were identified and their
      involvement in the Oas1b-mediated flavivirus resistance mechanism was analyzed.
      Initial difficulties in getting the two-hybrid assay to work with full-length
      Oas1b led to the discovery that this Oas protein uniquely has a C-terminal
      transmembrane domain that targets it to the endoplasmic reticulum (ER). Two
      peptides matching to oxysterol binding protein-related protein 1L (ORP1L) and ATP
      binding cassette protein 3, subfamily F (ABCF3), were identified as Oas1b
      interaction partners in yeast two-hybrid assays, and both in vitro
      transcribed/translated peptides and full-length proteins in mammalian cell
      lysates coimmunoprecipitated with Oas1b. Knockdown of a partner involved in Oas1b
      mediated antiflavivirus activity would be expected to increase flavivirus
      replication but not that of other types of viruses. However, RNA interference
      (RNAi) knockdown of ORP1L decreased the replication of the flavivirus West Nile
      virus (WNV) as well as that of other types of RNA viruses. This virus-nonspecific
      effect may be due to the recently reported dysregulation of late endosome
      movement by ORP1L knockdown. Knockdown of ABCF3 protein levels increased the
      replication of WNV but not that of other types of RNA viruses, and this effect on
      WNV replication was observed only in Oas1b-expressing cells. The results suggest
      that Oas1b is part of a complex located in the ER and that ABCF3 is a component
      of the Flv(r)-mediated resistance mechanism.

PMID- 22623794
TI  - Fluorescence resonance energy transfer-based intracellular assay for the
      conformation of hepatitis C virus drug target NS5A.
AB  - Nonstructural protein 5A (NS5A) is essential for hepatitis C virus (HCV)
      replication and assembly and is a critical drug target. Biochemical data suggest
      large parts of NS5A are unfolded as an isolated protein, but little is known
      about its folded state in the cell. We used fluorescence resonance energy
      transfer (FRET) to probe whether or not different regions of NS5A are in close
      proximity within the cell. Twenty-three separate reporter constructs were created
      by inserting one or more fluorophores into different positions throughout the
      three domains of NS5A. FRET efficiency was maximal when donor and acceptor
      fluorophores were positioned next to each other but also could be observed when
      the two fluorophores flanked NS5A domain 1 or domain 3. Informatic and
      biochemical analysis suggests that large portions of the carboxy terminus of NS5A
      are in an unfolded and disordered state. Quercetin, a natural product known to
      disrupt NS5A function in cells, specifically disrupted a conformationally
      specific domain 3 FRET signal. Intermolecular FRET indicated that the NS5A amino
      termini, but not other regions, are in close proximity in multimeric complexes.
      Overall, this assay provides a new window on the intracellular conformation(s) of
      NS5A and how the conformation changes in response to cellular and viral
      components of the replication and assembly complex as well as antiviral drugs.

PMID- 22623795
TI  - Role of nuclear factor-kappaB in oxidative stress associated with rabies virus
      infection of adult rat dorsal root ganglion neurons.
AB  - Recent studies in an experimental model of rabies showed major structural changes
      in the brain involving neuronal processes that are associated with severe
      clinical disease. Cultured adult rat dorsal root ganglion (DRG) neurons infected
      with the challenge virus standard-11 strain of rabies virus (CVS) showed axonal
      swellings and immunostaining for 4-hydroxy-2-nonenal (4-HNE), indicating evidence
      of lipid peroxidation associated with oxidative stress and reduced axonal growth
      compared to that of mock-infected DRG neurons. We have evaluated whether nuclear
      factor (NF)-kappaB might act as a critical bridge linking CVS infection and
      oxidative stress. On Western immunoblotting, CVS infection induced expression of
      the NF-kappaB p50 subunit compared to that of mock infection. Ciliary
      neurotrophic factor, a potent activator of NF-kappaB, had no effect on mock
      infected rat DRG neurons and reduced the number of 4-HNE-labeled puncta. SN50, a
      peptide inhibitor of NF-kappaB, and CVS infection had an additive effect in
      producing axonal swellings, indicating that NF-kappaB is neuroprotective. The
      fluorescent signal for subunit p50 was quantitatively evaluated in the nucleus
      and cytoplasm of mock- and CVS-infected rat DRG neurons. At 24 h postinfection
      (p.i.), there was a significant increase in the nucleus/cytoplasm ratio,
      indicating increased transcriptional activity of NF-kappaB, perhaps as a response
      to stress. At both 48 and 72 h p.i., there was significantly reduced nuclear
      localization of NF-kappaB. CVS infection may induce oxidative stress by
      inhibiting nuclear activation of NF-kappaB. A rabies virus protein may directly
      inhibit NF-kappaB activity. Further investigations are needed to gain a better
      understanding of the basic mechanisms involved in the oxidative damage associated
      with rabies virus infection.

PMID- 22623796
TI  - Human papillomavirus type 8 E6 oncoprotein inhibits transcription of the PDZ
      protein syntenin-2.
AB  - The E6 proteins from high-risk alpha human papillomavirus (HPV) types (e.g.,
      HPV16) are characterized by the presence of a PDZ-binding motif through which
      they interact with a number of cellular PDZ domain-containing substrates and
      cooperate in their degradation. The ability of these E6 proteins to bind to PDZ
      domain proteins correlates with the oncogenic potential of the virus. The E6
      proteins of oncogenic HPV from the genus Betapapillomavirus (betaPV, e.g., HPV8)
      do not encode a PDZ-binding motif. We found that the PDZ domain protein syntenin
      2 is transcriptionally downregulated in primary human epidermal keratinocytes
      (PHEK) by HPV8 E6. The mRNA levels of the known HPV16 E6 PDZ protein targets Dlg,
      Scribble, Magi-1, Magi-3, PSD95, and Mupp1 were not changed by HPV8 E6. Decreased
      protein levels of syntenin-2 were observed in cell extracts from PHEK expressing
      HPV5, -8, -16, -20, and -38 E6 but not in HPV1 and -4 E6-positive keratinocytes.
      Surprisingly, HPV16 E6 also repressed transcription of syntenin-2 but with a much
      lower efficiency than HPV8 E6. In healthy human skin, syntenin-2 expression is
      localized in suprabasal epidermal layers. In organotypic skin cultures, the
      differentiation-dependent expression of syntenin-2 was absent in HPV8 E6- and
      E6E7-expressing cells. In basal cell carcinomas of the skin, syntenin-2 was not
      detectable, whereas in squamous cell carcinomas, expression was located in
      differentiated areas. Short hairpin RNA-mediated knockdown of syntenin-2 led to
      an inhibition of differentiation and an increase in the proliferation capacity in
      PHEK. These results identified syntenin-2 as the first PDZ domain protein
      controlled by HPV8 and HPV16 at the mRNA level.

PMID- 22623797
TI  - Characterization of Magnaporthe oryzae chrysovirus 1 structural proteins and
      their expression in Saccharomyces cerevisiae.
AB  - Magnaporthe oryzae chrysovirus 1 (MoCV1), which is associated with an impaired
      growth phenotype of its host fungus, harbors four major proteins: P130 (130 kDa),
      P70 (70 kDa), P65 (65 kDa), and P58 (58 kDa). N-terminal sequence analysis of
      each protein revealed that P130 was encoded by double-stranded RNA1 (dsRNA1)
      (open reading frame 1 [ORF1] 1,127 amino acids [aa]), P70 by dsRNA4 (ORF4; 812
      aa), and P58 by dsRNA3 (ORF3; 799 aa), although the molecular masses of P58 and
      P70 were significantly smaller than those deduced for ORF3 and ORF4,
      respectively. P65 was a degraded form of P70. Full-size proteins of ORF3 (84 kDa)
      and ORF4 (85 kDa) were produced in Escherichia coli. Antisera against these
      recombinant proteins detected full-size proteins encoded by ORF3 and ORF4 in
      mycelia cultured for 9, 15, and 28 days, and the antisera also detected smaller
      degraded proteins, namely, P58, P70, and P65, in mycelia cultured for 28 days.
      These full-size proteins and P58 and P70 were also components of viral particles,
      indicating that MoCV1 particles might have at least two forms during vegetative
      growth of the host fungus. Expression of the ORF4 protein in Saccharomyces
      cerevisiae resulted in cytological changes, with a large central vacuole
      associated with these growth defects. MoCV1 has five dsRNA segments, as do two
      Fusarium graminearum viruses (FgV-ch9 and FgV2), and forms a separate clade with
      FgV-ch9, FgV2, Aspergillus mycovirus 1816 (AsV1816), and Agaricus bisporus virus
      1 (AbV1) in the Chrysoviridae family on the basis of their RdRp protein
      sequences.

PMID- 22623799
TI  - Suppression of the interferon and NF-kappaB responses by severe fever with
      thrombocytopenia syndrome virus.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious
      disease characterized by high fever, thrombocytopenia, multiorgan dysfunction,
      and a high fatality rate between 12 and 30%. It is caused by SFTS virus (SFTSV),
      a novel Phlebovirus in family Bunyaviridae. Although the viral pathogenesis
      remains largely unknown, hemopoietic cells appear to be targeted by the virus. In
      this study we report that human monocytes were susceptible to SFTSV, which
      replicated efficiently, as shown by an immunofluorescence assay and real-time
      reverse transcription-PCR. We examined host responses in the infected cells and
      found that antiviral interferon (IFN) and IFN-inducible proteins were induced
      upon infection. However, our data also indicated that downregulation of key
      molecules such as mitochondrial antiviral signaling protein (MAVS) or weakened
      activation of interferon regulatory factor (IRF) and NF-kappaB responses may
      contribute to a restricted innate immunity against the infection. NSs, the
      nonstructural protein encoded by the S segment, suppressed the beta interferon
      (IFN-beta) and NF-kappaB promoter activities, although NF-kappaB activation
      appears to facilitate SFTSV replication in human monocytes. NSs was found to be
      associated with TBK1 and may inhibit the activation of downstream IRF and NF
      kappaB signaling through this interaction. Interestingly, we demonstrated that
      the nucleoprotein (N), also encoded by the S segment, exhibited a suppressive
      effect on the activation of IFN-beta and NF-kappaB signaling as well. Infected
      monocytes, mainly intact and free of apoptosis, may likely be implicated in
      persistent viral infection, spreading the virus to the circulation and causing
      primary viremia. Our findings provide the first evidence in dissecting the host
      responses in monocytes and understanding viral pathogenesis in humans infected
      with a novel deadly Bunyavirus.

PMID- 22623798
TI  - Characterization of a viral phosphoprotein binding site on the surface of the
      respiratory syncytial nucleoprotein.
AB  - The human respiratory syncytial virus (HRSV) genome is composed of a negative
      sense single-stranded RNA that is tightly associated with the nucleoprotein (N).
      This ribonucleoprotein (RNP) complex is the template for replication and
      transcription by the viral RNA-dependent RNA polymerase. RNP recognition by the
      viral polymerase involves a specific interaction between the C-terminal domain of
      the phosphoprotein (P) (P(CTD)) and N. However, the P binding region on N remains
      to be identified. In this study, glutathione S-transferase (GST) pulldown assays
      were used to identify the N-terminal core domain of HRSV N (N(NTD)) as a P
      binding domain. A biochemical characterization of the P(CTD) and molecular
      modeling of the N(NTD) allowed us to define four potential candidate pockets on N
      (pocket I [PI] to PIV) as hydrophobic sites surrounded by positively charged
      regions, which could constitute sites complementary to the P(CTD) interaction
      domain. The role of selected amino acids in the recognition of the N-RNA complex
      by P was first screened for by site-directed mutagenesis using a polymerase
      activity assay, based on an HRSV minigenome containing a luciferase reporter
      gene. When changed to Ala, most of the residues of PI were found to be critical
      for viral RNA synthesis, with the R132A mutant having the strongest effect. These
      mutations also reduced or abolished in vitro and in vivo P-N interactions, as
      determined by GST pulldown and immunoprecipitation experiments. The pocket formed
      by these residues is critical for P binding to the N-RNA complex, is specific for
      pneumovirus N proteins, and is clearly distinct from the P binding sites
      identified so far for other nonsegmented negative-strand viruses.

PMID- 22623800
TI  - Human T-cell leukemia virus type 2 antisense viral protein 2 is dispensable for
      in vitro immortalization but functions to repress early virus replication in
      vivo.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are closely related but
      pathogenically distinct human retroviruses. The antisense strand of the HTLV-1
      genome encodes HTLV-1 basic leucine zipper (b-ZIP) protein (HBZ), a protein that
      inhibits Tax-mediated viral transcription, enhances T-cell proliferation, and
      promotes viral persistence. Recently, an HTLV-2 antisense viral protein (APH-2)
      was identified. Despite its lack of a typical b-ZIP domain, APH-2, like HBZ,
      interacts with cyclic AMP response element binding protein (CREB) and
      downregulates Tax-mediated viral transcription. Here, we provide evidence that
      the APH-2 C-terminal LXXLL motif is important for CREB binding and Tax
      repression. In order to investigate the functional role of APH-2 in the HTLV-2
      mediated immortalization of primary T lymphocytes in vitro and in HTLV-2
      infection in vivo, we generated APH-2 mutant viruses. In cell cultures, the
      immortalization capacities of APH-2 mutant viruses were indistinguishable from
      that of wild-type HTLV-2 (wtHTLV-2), indicating that, like HBZ, APH-2 is
      dispensable for viral infection and cellular transformation. In vivo, rabbits
      inoculated with either wtHTLV-2 or APH-2 mutant viruses established a persistent
      infection. However, the APH-2 knockout virus displayed an increased replication
      rate, as measured by an increased viral antibody response and a higher proviral
      load. In contrast to HTLV-1 HBZ, we show that APH-2 is dispensable for the
      establishment of an efficient infection and persistence in a rabbit animal model.
      Therefore, antisense proteins of HTLV-1 and HTLV-2 have evolved different
      functions in vivo, and further comparative studies will provide fundamental
      insights into the distinct pathobiologies of these two viruses.

PMID- 22623801
TI  - Subunit-selective mutational analysis and tissue culture evaluations of the
      interactions of the E138K and M184I mutations in HIV-1 reverse transcriptase.
AB  - The emergence of HIV-1 drug resistance remains a major obstacle in antiviral
      therapy. M184I/V and E138K are signature mutations of clinical relevance in HIV-1
      reverse transcriptase (RT) for the nucleoside reverse transcriptase inhibitors
      (NRTIs) lamivudine (3TC) and emtricitabine (FTC) and the second-generation (new)
      nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV),
      respectively, and the E138K mutation has also been shown to be selected by
      etravirine in cell culture. The E138K mutation was recently shown to compensate
      for the low enzyme processivity and viral fitness associated with the M184I/V
      mutations through enhanced deoxynucleoside triphosphate (dNTP) usage, while the
      M184I/V mutations compensated for defects in polymerization rates associated with
      the E138K mutations under conditions of high dNTP concentrations. The M184I
      mutation was also shown to enhance resistance to RPV and ETR when present
      together with the E138K mutation. These mutual compensatory effects might also
      enhance transmission rates of viruses containing these two mutations. Therefore,
      we performed tissue culture studies to investigate the evolutionary dynamics of
      these viruses. Through experiments in which E138K-containing viruses were
      selected with 3TC-FTC and in which M184I/V viruses were selected with ETR, we
      demonstrated that ETR was able to select for the E138K mutation in viruses
      containing the M184I/V mutations and that the M184I/V mutations consistently
      emerged when E138K viruses were selected with 3TC-FTC. We also performed
      biochemical subunit-selective mutational analyses to investigate the impact of
      the E138K mutation on RT function and interactions with the M184I mutation. We
      now show that the E138K mutation decreased rates of polymerization, impaired
      RNase H activity, and conferred ETR resistance through the p51 subunit of RT,
      while an enhancement of dNTP usage as a result of the simultaneous presence of
      both mutations E138K and M184I occurred via both subunits.

PMID- 22623802
TI  - Feline immunodeficiency virus Gag is a nuclear shuttling protein.
AB  - Lentiviral genomic RNAs are encapsidated by the viral Gag protein during virion
      assembly. The intracellular location of the initial Gag-RNA interaction is
      unknown. We previously observed feline immunodeficiency virus (FIV) Gag
      accumulating at the nuclear envelope during live-cell imaging, which suggested
      that trafficking of human immunodeficiency virus type 1 (HIV-1) and FIV Gag may
      differ. Here we analyzed the nucleocytoplasmic transport properties of both Gag
      proteins. We discovered that inhibition of the CRM1 nuclear export pathway with
      leptomycin B causes FIV Gag but not HIV-1 Gag to accumulate in the nucleus.
      Virtually all FIV Gag rapidly became intranuclear when the CRM1 export pathway
      was blocked, implying that most if not all FIV Gag normally undergoes nuclear
      cycling. In FIV-infected feline cells, some intranuclear Gag was detected in the
      steady state without leptomycin B treatment. When expressed individually, the FIV
      matrix (MA), capsid (CA), and nucleocapsid-p2 (NC-p2) domains were not capable of
      mediating leptomycin B-sensitive nuclear export of a fluorescent protein. In
      contrast, CA-NC-p2 did mediate nuclear export, with MA being dispensable. We
      conclude that HIV-1 and FIV Gag differ strikingly in a key intracellular
      trafficking property. FIV Gag is a nuclear shuttling protein that utilizes the
      CRM1 nuclear export pathway, while HIV-1 Gag is excluded from the nucleus. These
      findings expand the spectrum of lentiviral Gag behaviors and raise the
      possibility that FIV genome encapsidation may initiate in the nucleus.

PMID- 22623803
TI  - Cofilin 1-mediated biphasic F-actin dynamics of neuronal cells affect herpes
      simplex virus 1 infection and replication.
AB  - Herpes simplex virus 1 (HSV-1) invades the nervous system and causes pathological
      changes. In this study, we defined the remodeling of F-actin and its possible
      mechanisms during HSV-1 infection of neuronal cells. HSV-1 infection enhanced the
      formation of F-actin-based structures in the early stage of infection, which was
      followed by a continuous decrease in F-actin during the later stages of
      infection. The disruption of F-actin dynamics by chemical inhibitors
      significantly reduced the efficiency of viral infection and intracellular HSV-1
      replication. The active form of the actin-depolymerizing factor cofilin 1 was
      found to increase at an early stage of infection and then to continuously
      decrease in a manner that corresponded to the remodeling pattern of F-actin,
      suggesting that cofilin 1 may be involved in the biphasic F-actin dynamics
      induced by HSV-1 infection. Knockdown of cofilin 1 impaired HSV-1-induced F-actin
      assembly during early infection and inhibited viral entry; however,
      overexpression of cofilin 1 did not affect F-actin assembly or viral entry during
      early infection but decreased intracellular viral reproduction efficiently. Our
      results, for the first time, demonstrated the biphasic F-actin dynamics in HSV-1
      neuronal infection and confirmed the association of F-actin with the changes in
      the expression and activity of cofilin 1. These results may provide insight into
      the mechanism by which HSV-1 productively infects neuronal cells and causes
      pathogenesis.

PMID- 22623806
TI  - Editorial.

PMID- 22623807
TI  - Presidential address.

PMID- 22623808
TI  - Managing DICOM images: Tips and tricks for the radiologist.
AB  - All modalities in radiology practice have become digital, and therefore deal with
      DICOM images. Image files that are compliant with part 10 of the DICOM standard
      are generally referred to as "DICOM format files" or simply "DICOM files" and are
      represented as ".dcm." DICOM differs from other image formats in that it groups
      information into data sets. A DICOM file consists of a header and image data sets
      packed into a single file. The information within the header is organized as a
      constant and standardized series of tags. By extracting data from these tags one
      can access important information regarding the patient demographics, study
      parameters, etc. In the interest of patient confidentiality, all information that
      can be used to identify the patient should be removed before DICOM images are
      transmitted over a network for educational or other purposes. In addition to the
      DICOM format, the radiologist routinely encounters images of several file formats
      such as JPEG, TIFF, GIF, and PNG. Each format has its own unique advantages and
      disadvantages, which must be taken into consideration when images are archived,
      used in teaching files, or submitted for publication. Knowledge about these
      formats and their attributes, such as image resolution, image compression, and
      image metadata, helps the radiologist in optimizing the archival, organization,
      and display of images. This article aims to increase the awareness among
      radiologists regarding DICOM and other image file formats encountered in clinical
      practice. It also suggests several tips and tricks that can be used by the
      radiologist so that the digital potential of these images can be fully utilized
      for maximization of workflow in the radiology practice.

PMID- 22623809
TI  - Pictorial essay: Interventional radiology in the management of hemodialysis
      vascular access - A single-center experience.
AB  - Chronic kidney disease (CKD) is a worldwide public health problem and is
      associated with high morbidity and mortality. The majority of patients with CKD
      stage 5 (CKD-5), who cannot undergo renal transplant, depend on maintenance
      hemodialysis by surgically created access sites. Native fistulae are preferred
      over grafts due to their longevity. More than half of these vital portals for
      dialysis access will fail over time. Screening procedures to select high-risk
      patients before thrombosis or stenosis appears have resulted in aggressive
      management. These patients are referred for angiographic evaluation and/or
      therapy. We present the patterns of dialysis-related interventions done in our
      institution.

PMID- 22623810
TI  - Percutaneous transhepatic embolization of biliary leakage with N-butyl
      cyanoacrylate.
AB  - Biliary leakage is a known complication after biliary surgery. In this report, we
      describe an uncommon treatment of a common biliary complication, wherein we used
      percutaneous transhepatic injection of N-butyl cyanoacrylate (NBCA) to treat a
      biliary leak in an 83-year-old patient.

PMID- 22623811
TI  - Case report: Percutaneous treatment of multiple honeycomb-like liver hydatid
      cysts (type III CE2, according to WHO classification).
AB  - Percutaneous treatment has been developing as a reliable and effective
      alternative to surgery in the treatment of liver hydatid cysts. However,
      percutaneous treatment is strongly recommended only for some types of hydatid
      cysts (types I and II). We report a patient with type III (CE2, according to the
      WHO classification) multiple liver hydatid cysts treated with the PAIR (puncture
      aspiration-injection-reaspiration) technique. The patient developed a secondary
      biliary fistula, which ultimately healed.

PMID- 22623812
TI  - Bursae around the knee joints.
AB  - A bursa is a fluid-filled structure that is present between the skin and tendon
      or tendon and bone. The main function of a bursa is to reduce friction between
      adjacent moving structures. Bursae around the knee can be classified as those
      around the patella and those that occur elsewhere. In this pictorial essay we
      describe the most commonly encountered lesions and their MRI appearance.

PMID- 22623814
TI  - Myositis ossificans imaging: keys to successful diagnosis.
AB  - Myositis ossificans (MO) is an inflammatory pseudotumor of the muscle that may be
      mistaken clinically and even histologically for a malignant soft tissue tumor.
      The aim of this article is to report the imaging characteristics of MO, the
      emphasis being on the early diagnostic clues. USG can be used at an early stage
      to reveal the 'zone phenomenon,' which is highly suggestive of MO. A short course
      of nonsteroidal anti-inflammatory drug therapy may be an efficient treatment for
      early MO.

PMID- 22623813
TI  - Pictorial essay: Role of ultrasound in failed carpal tunnel decompression.
AB  - USG has been used for the diagnosis of carpal tunnel syndrome. Scarring and
      incomplete decompression are the main causes for persistence or recurrence of
      symptoms. We performed a retrospective study to assess the role of ultrasound in
      failed carpal tunnel decompression. Of 422 USG studies of the wrist performed at
      our center over the last 5 years, 14 were for failed carpal tunnel decompression.
      Scarring was noted in three patients, incomplete decompression in two patients,
      synovitis in one patient, and an anomalous muscle belly in one patient. No
      abnormality was detected in seven patients. We present a pictorial review of USG
      findings in failed carpal tunnel decompression.

PMID- 22623804
TI  - Unexpected maintenance of hepatitis C viral diversity following liver
      transplantation.
AB  - Chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis in up to
      20% of individuals, often requiring liver transplantation. Although the new liver
      is known to be rapidly reinfected, the dynamics and source of the reinfecting
      virus(es) are unclear, resulting in some confusion concerning the relationship
      between clinical outcome and viral characteristics. To clarify the dynamics of
      liver reinfection, longitudinal serum viral samples from 10 transplant patients
      were studied. Part of the E1/E2 region was sequenced, and advanced phylogenetic
      analysis methods were used in a multiparameter analysis to determine the history
      and ancestry of reinfecting lineages. Our results demonstrated the complexity of
      HCV evolutionary dynamics after liver transplantation, in which a large diverse
      population of viruses is transmitted and maintained for months to years. As many
      as 30 independent lineages in a single patient were found to reinfect the new
      liver. Several later posttransplant lineages were more closely related to older
      pretransplant viruses than to viruses detected immediately after transplantation.
      Although our data are consistent with a number of interpretations, the
      persistence of high viral genetic variation over long periods of time requires an
      active mechanism. We discuss possible scenarios, including frequency-dependent
      selection or variation in selective pressure among viral subpopulations, i.e.,
      the population structure. The latter hypothesis, if correct, could have relevance
      to the success of newer direct-acting antiviral therapies.

PMID- 22623815
TI  - Pictorial essay: Non-coronary applications of cardiac CT.
AB  - Recent advances in scanner technology have enabled computed tomography (CT) scan
      to evolve into a valuable tool in the noninvasive evaluation of coronary artery
      disease. Due to its high negative predictive value, CT can act as a gatekeeper,
      determining which patients require cardiac catheterization. Although mainly used
      for the evaluation of coronary artery disease, cardiac CT is also useful in the
      evaluation of various non-coronary cardiac conditions involving the pericardium,
      pulmonary veins, and the coronary veins and valves, as well as in the assessment
      of cardiomyopathies, masses, and ventricular and valvular function. This review
      discusses and illustrates the various non-coronary applications of cardiac CT.

PMID- 22623816
TI  - In the workup of patients with obscure gastrointestinal bleed, does 64-slice MDCT
      have a role?
AB  - PURPOSE: The purpose was to prospectively determine the sensitivity of 64-slice
      MDCT in detecting and diagnosing the cause of obscure gastrointestinal bleed
      (OGIB). MATERIALS AND METHODS: Our study included 50 patients (male 30, female
      20) in the age range of 3-82 years (average age: 58.52 years) who were referred
      to our radiology department as part of their workup for clinically evident
      gastrointestinal (GI) bleed or as part of workup for anemia (with and without
      positive fecal occult blood test). All patients underwent conventional upper
      endoscopy and colonoscopy before undergoing CT scan. Following a noncontrast
      scan, all patients underwent triple-phase contrast CT scan using a 64-slice CT
      scan system. The diagnostic performance of 64-slice MDCT was compared to the
      results of capsule endoscopy, 99m-technetium-labeled red blood cell scintigraphy
      (99mTc-RBC scintigraphy), digital subtraction angiography, and surgery whenever
      available. RESULTS: CT scan showed positive findings in 32 of 50 patients. The
      sensitivity, specificity, positive predictive value, and negative predictive
      values of MDCT for detection of bleed were 72.2%, 42.8%, 81.2%, and 44.4%,
      respectively. Capsule endoscopy was done in 15 patients and was positive in 10
      patients; it had a sensitivity of 71.4%. Eleven patients had undergone 99mTc-RBC
      scintigraphy prior to CT scan, and the result was positive in seven patients
      (sensitivity 70%). Digital subtraction angiography was performed in only eight
      patients and among them all except one patient showed findings consistent with
      the lesions detected on MDCT. CONCLUSION: MDCT is a sensitive and noninvasive
      tool that allows rapid detection and localization of OGIB. It can be used as the
      first-line investigation in patients with negative endoscopy and colonoscopy
      studies. MDCT and capsule endoscopy have complementary roles in the evaluation of
      OGIB.

PMID- 22623817
TI  - CT scan diagnosis of hepatic adenoma in a case of von Gierke disease.
AB  - Hepatic adenoma is a well-defined, benign, solitary tumor of the liver. In
      individuals with glycogen storage disease I, adenoma tends to occur at a
      relatively younger age and can be multiple (adenomatosis). Imaging plays a
      pivotal role in diagnosing hepatic adenoma and in differentiating adenoma from
      other focal hepatic lesions. Especially in patients with von Gierke disease, in
      addition to the associated hepatomegaly caused by steatohepatitis and the
      diffusely reduced attenuation of the liver parenchyma seen on CT, there may be
      more than one hepatic adenoma in up to 40% of patients. Malignant degeneration of
      hepatic adenoma into hepatocellular carcinoma can occur and hence imaging is
      important for prompt diagnosis of adenoma and its complications. In this case
      report, we present a case of liver adenoma diagnosed by CT scan in a patient with
      von Gierke disease.

PMID- 22623818
TI  - Multifocal intracranial astrocytoma in a pediatric patient with Ollier disease.
AB  - Ollier disease (OD) is a subtype of enchondromatosis. Historically, it has been
      distinguished from Maffucci syndrome (MS) by the presence of vascular
      malformations and nonskeletal neoplasms (NSN) in the latter. However, there is an
      increasing number of reports of NSN in OD, and this categorization is now being
      questioned. We report a case of OD complicated by multifocal astrocytoma in a
      young patient, once again pointing to a possible association between OD and NSN.
      We also review the available literature and examine the similarities between the
      reported cases.

PMID- 22623819
TI  - Utility of gray-scale ultrasound to differentiate benign from malignant thyroid
      nodules.
AB  - OBJECTIVE: The objective was to assess the utility of gray-scale USG to identify
      patterns of thyroid nodules and to correlate the characteristics of benign and
      malignant nodules with pathological diagnosis. MATERIALS AND METHODS: From
      September 2009 to August 2010, a total of 203 patients (17 males and 186
      females), with 240 nodules detected at USG, were included in this study. The
      characteristics of each nodule were determined. The results were then compared
      with fine needle aspiration (FNA)/histopathological diagnosis. RESULTS: Of the
      240 nodules examined, 44 (18.33%) were found to be malignant on cytopathology.
      The malignant nodules demonstrated solid or predominantly solid composition
      (sensitivity 88.6%, specificity 53.5%); presence of microcalcification
      (sensitivity 65.9%, specificity 97.9%); irregular or poorly defined margins
      (sensitivity 84%, specificity 88.7%); anteroposterior (AP) diameter > transverse
      diameter (sensitivity 77.2%, specificity 80.1%); absent or thick incomplete halo
      (sensitivity 70.4%, specificity 65.8%); and markedly hypoechoic character
      (sensitivity 65.9%, specificity 84.6%). Among males, malignant nodules were found
      in 36.8%, whereas in females the occurrence was 16.7%. CONCLUSION: Gray-scale USG
      features of thyroid nodules are useful to distinguish patients with clinically
      significant thyroid nodules from those with innocuous nodules despite the overlap
      of findings. From our study, it is apparent that the USG findings of poorly
      defined margins, marked hypoechogenicity, microcalcifications, and a taller-than
      wider shape have a high diagnostic accuracy for identifying malignant thyroid
      nodules.

PMID- 22623821
TI  - Impact of RTI act: It is time to synchronize computer clocks.

PMID- 22623820
TI  - MRI evaluation of the contralateral breast in patients with recently diagnosed
      breast cancer.
AB  - INTRODUCTION: Contralateral breast cancer can be synchronous and/or metachronous
      in patients with cancer of one breast. Detection of a synchronous breast cancer
      may affect patient management. Dynamic contrast-enhanced MRI of the breast (DCE
      MRI) is a sensitive technique for detecting contralateral lesions occult on the
      other imaging modalities in women already diagnosed with cancer of one breast.
      AIM: The aim was to assess the incidence of mammographically occult synchronous
      contralateral breast cancer in patients undergoing MRI mammography for the
      evaluation of a malignant breast lesion. MATERIALS AND METHODS: A total of 294
      patients with recently diagnosed breast cancer who underwent MRI of the breast
      were evaluated for lesions in the opposite breast. RESULTS: The incidence of
      synchronous contralateral malignancy detected by preoperative MRI mammography
      done for evaluation of extent of disease was 4.1%. CONCLUSION: Preoperative
      breast MRI may detect clinically and mammographically occult synchronous
      contralateral cancer, and can help the patient avoid an additional second surgery
      or a second course of chemotherapy later; also, as theoretically these lesions
      are smaller, there may be a survival benefit as well.

PMID- 22623822
TI  - Heavily T2W 3D-SPACE images for evaluation of cerebrospinal fluid containing
      spaces.

PMID- 22623823
TI  - The role of laparoscopic surgery in gastric cancer.
AB  - The laparoscopic surgery in gastric cancer is applied with increasing frequency
      nowadays; noticeable reports come mainly from Korea and Japan with satisfactory
      results. This review presents briefly the issue by evaluating its role. A PubMed
      search of relevant articles published up to 2010 was performed to identify
      current information. Most data come from Far East, where gastric cancer occurs
      more often, and the proportion of early gastric cancer is high. Laparoscopic
      approach includes both the diagnostic laparoscopy and laparoscopic resection.
      Laparoscopic gastrectomy has currently limited application for gastric cancer in
      the West; it is not widely accepted and raises important considerations
      necessitating the planning of multicentre randomised control trials based mainly
      on the long-term results.

PMID- 22623824
TI  - A prospective nonrandomized comparison of laparoscopic Nissen fundoplication and
      laparoscopic Toupet fundoplication in Indian population using detailed objective
      and subjective criteria.
AB  - BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is a commonly performed
      procedure for the treatment of gastro esophageal reflux disease (GERD) worldwide.
      However, unfavourable postoperative sequel, including gas bloat and dysphagia,
      has encouraged surgeons to perform alternative procedures such as laparoscopic
      Toupet fundoplication (LTF). This prospective nonrandomized study was designed to
      compare LNF with LTF in patients with GERD. MATERIALS AND METHODS: Hundred and
      ten patients symptomatic for GERD were included in the study after having
      received intensive acid suppression therapy for a minimum of 8 weeks. A 24-hour
      pH metry was done on all patients. Fifty patients having reflux on 24-hour pH
      metry were taken up for the surgery. Patients were further divided into group-A
      (LNF) and group-B (LTF). RESULTS: The median percentage time with esophageal pH <
      4 decreased from 10.18% and 12.31% preoperatively to 0.85% and 1.94%
      postoperatively in LNF and LTF-groups, respectively. There was a significant and
      comparable increase in length of lower esophageal sphincter (LES), length of
      intraabdominal part of LES and LES pressure at respiratory inversion point in
      both the groups. In LNF-group, five patients had early dysphagia that improved
      afterwards. There were no significant postoperative complications. CONCLUSION:
      LNF and LTF are highly effective in the management of GERD with significant
      improvement in symptoms and objective parameters. LNF may be associated with
      significantly higher incidence of short onset transient dysphagia that improves
      with time. Patients in both the groups showed excellent symptom and objective
      control on 24-hour pH metry on short term follow-up.

PMID- 22623825
TI  - Role of diagnostic laparoscopy in assessing operability in borderline resectable
      gastrointestinal cancers.
AB  - BACKGROUND: Diagnostic laparoscopy helps in diagnosing and staging
      Gastrointestinal (GI) cancers. Routine laparoscopy before laparotomy, especially
      in cancers that have equivocal operability, helps to avoid unnecessary
      laparotomies. Present study evaluates utility of laparoscopy in diagnosing and
      staging GI cancers. MATERIALS AND METHODS: Diagnostic laparoscopy was done in 41
      patients with gastrointestinal (GI) cancers who were thought to have equivocal
      operability. Patients with suspected or known non-metastatic GI cancers, in whom
      resectability was found doubtful by clinical assessment and pre-operative
      imaging, were included. Patients with non-GI cancers (lymphoma, gynaecologic
      cancers, genitourinary cancers, retroperitoneal sarcoma, sarcoma and abdominal
      metastasis of non-GI cancers) and metastatic cancers which were beyond the scope
      of curative surgery were excluded from the study. RESULTS: After diagnostic
      laparoscopy (DL) five patients had benign diagnosis. Out of 36 patients with
      malignant diagnosis, after DL, 22 patients (61.1%) were inoperable, 11 patients
      (30.6%) were operable, and three (8.3%) patients were of equivocal operability.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value of laparoscopy in detecting operability were 100%, 91.7%, 81.8%, and 100%,
      respectively. CONCLUSIONS: Laparoscopy helped in a significant number of patients
      with advanced GI cancers to avoid laparotomy. The morbidity of DL was acceptable.

PMID- 22623826
TI  - Type-I complex regional pain syndrome of umbilical port site: An unforeseen
      complication of laparoscopic surgery.
AB  - Many complications have been observed after laparoscopic surgery. Persisting pain
      in the umbilical port site is due to infection, hernia, endometriosis,
      metastasis, etc. There is no case report due to neuralgic complex regional pain
      syndrome, and we have dealt a case which is described with relevant literature
      review and etiopathogenesis.

PMID- 22623827
TI  - Laparoscopic management of massive spontaneous external haemorrhage from the
      umbilical varix due to recanalisation of the paraumbilical vein in a patient with
      'Child's Class A' liver cirrhosis.
AB  - Spontaneous external haemorrhage from the umbilical varix is an extremely rare
      complication of portal hypertension. Bleeding is usually into the peritoneal
      cavity and the treatment involves urgent laparotomy and ligation of the bleeding
      varices. We describe a cirrhotic 38-year-old man who presented with spontaneous
      external haemorrhage from the umbilical varix which was successfully managed
      laparoscopically by in-situ distal clipping and proximal transcutaneous ligation
      of the recanalised paraumbilical veins. We therefore feel that laparoscopy can be
      safely and effectively employed to control external haemorrhage from the
      umbilical varix associated with liver cirrhosis. This novel technique can help
      avoid a laparotomy and also help preserve the umbilicus.

PMID- 22623828
TI  - Laparoscopic excision of a giant mesothelial omental cyst.
AB  - A 42-year-old patient presented with right-sided abdominal discomfort.
      Investigations revealed a 19 * 21 centimetres large cystic lesion occupying
      nearly the entire right side of the abdomen. It was situated between ascending
      colon and right kidney and extended from the liver to the pelvic inlet supero
      inferiorly. Laparoscopic excision was planned. The cyst was aspirated completely
      and dissected from the surrounding structures. It was eventually found to be
      arising from the right free edge of the greater omentum. Due to its size and
      weight it was lodged behind the ascending colon. Post-operative course was
      uneventful. Histology revealed a mesothelial omental cyst. Omental cysts are rare
      abdominal tumours. Complete excision is the treatment advised to prevent
      recurrence. Laparoscopic excision can be safely performed taking care to
      ascertain diagnosis and not to damage any structures intra-operatively.

PMID- 22623829
TI  - Laparoscopic resection of giant liver hemangioma using laparoscopic Habib probe
      for parenchymal transection.
AB  - Experience with laparoscopic liver resections is limited. Laparoscopic resection
      of a variety of liver lesions has been reported and is considered appropriate for
      lesions in the left lateral segment and inferior segments of the right lobe.
      Herein, we report a 52-year-old male patient who underwent a laparoscopic
      resection of giant liver hemangioma with the use of a laparoscopic 4* Habib
      probe.

PMID- 22623830
TI  - Endoscopic single-port "components separation technique" for postoperative
      abdominal reconstruction.
AB  - BACKGROUND: In 1990, Ramirez introduced a new procedure to close abdominal wall
      hernia (AWH), called "components separation technique (CST)". Thanks to
      endoscopy, surgical repair possibilities have risen, reducing the operative
      trauma and preserving vascular and neuronal anatomical structures. This report
      aims to describe a single port endoscopic approach for CST to repair the
      abdominal wall of a patient undergoing surgery for abdominal aneurysm and already
      subject to placement of a mesh for AWH. METHODS: We performed endoscopic-assisted
      CST, using a single-port access with a gasless technique. CONCLUSION: CST is a
      useful procedure to close large abdominal wall incisional hernia avoiding the use
      of mesh, notably under contamination, when prosthetic material use is
      contraindicated. The endoscopic-assisted CST produces same results than the
      conventional open separation technique and also minimised tissue trauma that
      ensures blood supply and prevents postoperative wounds complications. The
      described single port method was found to be safe and effective to close large
      midline abdominal hernias when a primary open or laparoscopic closure is not
      feasible or when patients have been previously treated with abdominal meshes.

PMID- 22623831
TI  - Laparoscopic cholecystectomy and appendicectomy in situ inversus totalis.

PMID- 22623832
TI  - Laparoscopic perforostomy for treating a delayed colonoscopic perforation: Novel
      approach.

PMID- 22623833
TI  - Rare blood donor program in the country: Right time to start.

PMID- 22623834
TI  - Red cell phenotyping of blood from donors at the National blood center of
      Malaysia.
AB  - BACKGROUND: Human blood groups are polymorphic and inherited integral structures
      of the red cell membrane. More than 300 red cell antigens have been identified
      and further categorized into 30 major discrete systems. Their distribution varies
      in different communities and ethnic groups. AIMS: This work was set to determine
      the prevalence of red cell phenotypes in donors from the major ethnic groups in
      Malaysia, namely, Malays, Chinese, and Indians. MATERIALS AND METHODS: The work
      utilized the dextran acrylamide gel technique in which four types of gel cards
      were used to identify the blood groups of 594 subjects collected at the National
      Blood Transfusion Centre, Malaysia. RESULTS: Blood group O and CDe/CDe (R1R1)
      were the most common in all ethnic groups. The cde/cde (rr) was more prevalent
      amongst Indians. The rare phenotypes found were cDE/cDE(R2R2) and cDE/CDE(R2Rz).
      With the Lewis system, the distribution of Le(a-b+) was similar among the ethnic
      groups. The rarest phenotype Fy(a-b-) was discovered in two donors. Jk(a-b-) was
      found in seven Malays and in two Indians. In the MNSs system, MN was common in
      Malays and Chinese, while the MM was more common among Indians. The rare SS was
      found in 19 donors. Malay and Chinese subjects had high P1 Negative blood but
      Indians showed high P1 positive blood. Within the Kell System, the very rare KK
      type was found in six subjects. CONCLUSIONS: The results obtained serve as an
      established database for the distribution of red cell phenotypes based on the
      blood group systems of donors from the major ethnic groups in Malaysia.

PMID- 22623835
TI  - Hepatitis B core antibody testing in Indian blood donors: A double-edged sword!
AB  - BACKGROUND: Until lately, anti-HBc antibodies were considered an effective marker
      for occult Hepatitis B virus (HBV) infection and have served their role in
      improving blood safety. But, with the development of advanced tests for HBV DNA
      detection, the role of anti-HBc in this regard stands uncertain. MATERIALS AND
      METHODS: Anti-HBc and HBsAg ELISA and ID-NAT tests were run in parallel on donor
      blood samples between April 1, 2006 and December 31, 2010 at the Department of
      Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi. A positive ID-NAT
      was followed by Discriminatory NAT assay. RESULTS: A total of 94 247 samples were
      tested with a total core positivity rate of 10.22%. We identified nearly 9.17% of
      donors who were reactive for anti-HBc and negative for HBsAg and HBV DNA. These
      are the donors who are potentially non-infectious and may be returned to the
      donor pool. CONCLUSION: Although anti HBc testing has a definite role in
      improving blood safety, centers that have incorporated NAT testing may not derive
      any additional benefit by performing anti-HBc testing, especially in resource
      limited countries like ours.

PMID- 22623836
TI  - Recombinant-activated factor VII in patients with uncontrolled bleeding: A
      retrospective observational analysis.
AB  - BACKGROUND: Factor VIIa (recombinant) has an off-label use to control life
      threatening bleeding that is refractory to other measures and was shown to
      decrease transfusion requirements. OBJECTIVE: The primary objective of this study
      was to assess the safety and effectiveness of factor VIIa (recombinant) on blood
      transfusion requirements and coagulation parameters when used in patients whose
      bleeding was uncorrected by other means. The pharmacoeconomic impact for any
      discrepancy from our protocol was evaluated. Secondary outcomes included 4-hour
      and 28-day mortality, as well as safety of this agent in terms of thromboembolic
      complications. MATERIALS AND METHODS: We retrospectively evaluated patients who
      received recombinant-activated factor VII (rFVIIa) for uncontrolled bleeding from
      June 2008 to April 2011. The medical records of 33 patients were evaluated.
      Coagulation parameters and blood products were determined 24 hours before and 24
      hours after administration of rFVIIa, and the results compared. Patients were
      also screened for any thromboembolic complications. RESULTS: Administration of
      rFVIIa reduced blood transfusion requirements and improved coagulation parameters
      significantly (P<0.05). No thromboembolic complications were reported. Most of
      the dosing was consistent with those recommended in our institutional protocol,
      with discrepancies resulting in an average cost of $56 058. Moreover, pH was
      reported in only 67% of patients. All patients treated with rFVIIa survived up to
      4 hours after receiving this agent, while the 28-day mortality was 24% (8/33).
      CONCLUSION: The use of rFVIIa appears to be safe and effective in promoting
      hemostasis, as evident from reducing transfusion requirements and improving the
      coagulation variables.

PMID- 22623837
TI  - Quality indicators for discarding blood in the National Blood Center, Kuala
      Lumpur.
AB  - BACKGROUND AND OBJECTIVE: The implementation of quality system and continuous
      evaluation of all activities of the Blood Transfusion Services (BTS) can help to
      achieve the maximum quantity and quality of safe blood. Optimizing blood
      collection and processing would reduce the rate of discard and improve the
      efficiency of the BTS. The objective of this study is to determine the rate of
      discard of blood and blood component and identify its reasons at the National
      Blood Centre (NBC), Kuala Lumpur, during the year of 2007 in order to introduce
      appropriate intervention. STUDY DESIGNS AND METHODS: Data on the number of
      discarded whole blood units and its components, reasons for discard, and the
      number of blood components processed as well as the number of collected blood
      units were obtained from the Blood Bank Information System - NBC database. These
      were analyzed. RESULTS: The total number of blood units collected in 2007 was
      171169 from which 390636 units of components were prepared. The total number of
      discarded whole blood units and its components was 8968 (2.3%). Platelet
      concentrate recorded the highest of discard at 6% (3909) followed by whole blood
      at 3.7% (647), fresh frozen plasma (FFP) at 2.5% (2839), and cryoprecipitate at
      2% (620). The rate of discarded packed red blood cells RBCs, plasma aphaeresis,
      and PLT aphaeresis was less than 1% at 0.6% (902), 0.6% (37), and 0.29% (14),
      respectively. RBC contamination of PLT and plasma were the major cause of discard
      at 40% (3558). Other causes include leakage (26% - 2306), lipemia (25% - 2208),
      and underweight (4% - 353). CONCLUSION: Good donor selection, training and
      evaluation of the staff, as well as implementation of automation will help to
      improve processes and output of BTS. This would reduce discard of blood
      components and wastage caused by non conformance.

PMID- 22623838
TI  - Distinct immunoregulatory cytokine pattern in Egyptian patients with occult
      Hepatitis C infection and unexplained persistently elevated liver transaminases.
AB  - BACKGROUND/AIM: The immunopathogenesis of occult Hepatitis C virus (HCV)
      infection is a matter of great controversy and has been suggested to involve a
      complex balance between cytokines with pro- and anti-inflammatory activity. This
      work aimed at studying the serum Th1 and Th2 cytokine production in patients with
      occult HCV infection. MATERIALS AND METHODS: Serum levels of cytokines of Th1
      (interleukin [IL]-2, INF-gamma) and Th2 (IL-4) were measured in 27 patients with
      occult HCV infection and 28 patients with chronic hepatitis C infection. RESULTS:
      The levels of IL-2 and interferon-gamma were highly significantly increased in
      patients with chronic HCV infection (P<0.001). IL-4 was highly significantly
      increased in occult HCV infection (P<0.001). Significant increases were noted in
      chronic HCV infection regarding bilirubin (P<0.001), ALT (P = 0.009), AST (P =
      0.013), AFP (P<0.001), while serum albumin was significantly higher in occult HCV
      infection (P<0.001). Necroinflammation (P<0.001), fibrosis (P<0.001), and
      cirrhosis (P = 0.03) were significantly increased in chronic HCV infection.
      CONCLUSION: Our data revealed a high prevalence of occult HCV infection (25%) in
      patients with unexplained persistently abnormal liver function test results.
      Those patients exhibited a distinct immunoregulatory cytokine pattern, favoring
      viral persistence and explaining the less aggressive course of this disease
      entity than chronic HCV infection.

PMID- 22623839
TI  - Family/friend donors are not true voluntary donors.
AB  - BACKGROUND: Family/replacement donors still provide more than 45% of the blood
      collected in India. National AIDS Control Organization passed the guideline that
      family/friend donors should be considered as voluntary donors by the blood banks
      in India. MATERIALS AND METHODS: We did a prospective analysis of Transfusion
      Transmitted Infections (TTI's) on our family donors for the years 2009 and 2010
      to compare the results and evaluate if family donors are as safe as voluntary
      donors. RESULT: The prevalence of Human Immunodeficiency Virus, Hepatitis B
      surface antigen, Hepatitis C Virus, and Anti-Treponema Palladium antibody was
      much higher in family donors in comparison to voluntary donors. CONCLUSION:
      Family donors cannot be included amongst voluntary-non-remunerated blood donors
      as they have a higher rate of TTIs.

PMID- 22623840
TI  - Comparative study of Treponemal and non-Treponemal test for screening of blood
      donated at a blood center.
AB  - The non-Treponemal tests such as Rapid Plasma Reagin test (RPR) or the Venereal
      Disease Reference Laboratory test are the most commonly used test for screening
      of syphilis in the blood centers in India. Now, with the availability of Enzyme
      linked immunosorbent assay (ELISA) and Immunochromatographic assays in the
      market, we decided to evaluate these assays in comparison with Treponema pallidum
      Haemagglutination Assay (TPHA) which was considered as a gold standard for this
      study. A total of 8 685 samples of voluntary blood donors were tested on
      Trepolisa 3.0 and then the initially reactive samples were retested in duplicate
      on the same assay as well as on Omega Pathozyme, RPR, RAPHA (Rapid Anti-Treponema
      pallidum Assay), and TPHA. Of the 158 initially reactive samples, 104 were
      repeatedly reactive on the same assay, 85 were reactive with RPR, 77 were
      reactive with RAPHA, 60 were reactive on Omega, and 53 were confirmed reactive on
      TPHA. 48 (56.4%) of the results on RPR were biological false positive, while
      21.9% of results were false negative on RPR. We evaluated that Omega Pathozyme
      was quite in agreement with TPHA as compared with Trepolisa 3.0, RAPHA, and RPR.
      We concluded that Omega Pathozyme (ELISA) can be considered as a suitable test
      for screening of syphilis in a blood center.

PMID- 22623841
TI  - Red blood transfusion in preterm infants: changes in glucose, electrolytes and
      acid base balance.
AB  - BACKGROUND: Preterm neonates comprise the most heavily transfused group of
      patients, and about 85% of extremely low birth weight newborns receive a
      transfusion by the end of their hospital stay. The aim of this study was to
      assess the possible metabolic effects of RBC transfusion on preterm infants,
      especially during the first 2 weeks of life, and its relation to blood volume.
      MATERIALS AND METHODS: This study was conducted on 40 preterm neonates with
      gestational age of less than or equal to 34 weeks. They received RBCs transfusion
      during first 2 weeks of life. Venous blood samples of infants were collected 2 to
      4 hours before and 1 hour after the end of transfusion to evaluate hemoglobin
      (Hb) level, hematocrit, acid-base, electrolytes, and glucose status. Then,
      infants were classified into two main groups: those who received RBCs volume less
      than or 20 ml/kg and those who received RBCs volume more than 20 ml/kg. RESULTS:
      Infants received a mean volume of 20.38 +/- 3.2 ml/kg RBCs (range, 10.9 - 26.6
      ml/kg) at a median age of 9.8 +/- 3.6 days. After transfusion, a significant
      increase of mean Hb (P<0.001), mean Hct (P<0.001), pH (P<0.001), pO(2) (P<0.05),
      and a significant decrease of the pCO2 (41.46 +/- 8.8torr vs 35.4 +/- 9.34 torr;
      P<0.001) were observed. In addition, there was a significant increase of serum
      K(+) (P<0.001), and a significant decrease of Ca(+2) (P<0.001). A positive
      correlation was found between the K(+) intake and the changes of kalemia (r =
      0.99; P = 0.00). Furthermore, we observed an inverse correlation between the
      patients' calcium intake and the changes of calcemia (r = -0.35; P = 0.02). On
      comparing the changes in clinical and biochemical variables between two groups
      after transfusion, we observed a significant increase in mean Hb and Hct
      associated with a significant decrease in mean serum Ca(+2) (P<0.001) in the
      group receiving the larger blood volume. CONCLUSION: RBC transfusion was
      effective in improving anemia, oxygenation, increasing pH, and decreasing CO(2)
      and Ca(+2). However, from a more clinically relevant point of view, we
      demonstrated the development of hyperkalemia, especially in infants with a
      previously borderline hyperkalemia.

PMID- 22623842
TI  - A profile of rare bloods in India and its impact in blood transfusion service.
AB  - From transfusion point of view, a rare blood is the one which lacks a high
      frequency antigen as well as the one who lacks multiple common antigens and such
      blood donations help in transfusion to those recipients having alloantibodies to
      corresponding antigens. In India, we have about four such kinds of phenotypes
      potential enough to pose problems in providing blood to the recipients having
      these phenotypes. Besides, there are other four kinds of rare bloods that pose
      seldom problems in blood supply, though some of these may cause problems in
      interpretation of results on assigning proper blood groups for a person.

PMID- 22623843
TI  - Nonspecific red cell aggregation interferes in the interpretation of gel test
      results.

PMID- 22623844
TI  - Hematological evaluation of acquired von Willebrand syndrome before oral surgery:
      Management of an unusual case.

PMID- 22623845
TI  - Mechanism and pathophysiology of activated protein C-related factor V leiden in
      venous thrombosis.

PMID- 22623846
TI  - A near-miss hemolytic transfusion reaction and hemolytic disease of the newborn
      due to anti-c antibodies in a Rh (D)-positive mother: Implications for
      immunohematological management in pregnancy.

PMID- 22623847
TI  - Transfusion requirement during dengue fever epidemic in a rural medical college
      in south India.

PMID- 22623848
TI  - A study on optimization of plasma pool size for viral infectious markers in
      Indian blood donors using nucleic acid amplification testing.

PMID- 22623849
TI  - Frequency of ABO and rhesus blood groups in blood donors.

PMID- 22623850
TI  - Anti-Leb (Lewis) antibody in renal transplantation, emphasizing the role of
      transfusion medicine in organ transplantation.

PMID- 22623851
TI  - ABO and Rhesus blood groups in potential blood donors at Durgapur Steel city of
      the district of Burdwan, West Bengal.

PMID- 22623852
TI  - Transfusion-transmissible infections among voluntary blood donors at Government
      Medical College Thiruvananthapuram, Kerala, India.

PMID- 22623853
TI  - Reversible cerebral angiopathy after blood transfusion.

PMID- 22623854
TI  - A potpourri of ocular disorders.

PMID- 22623855
TI  - Screening and public health strategies for diabetic retinopathy in the Eastern
      Mediterranean region.
AB  - Diabetic retinopathy (DR) is a complication of diabetes mellitus that can cause
      blindness. As the prevalence of diabetes increases globally and patients live
      longer, the cases of DR are increasing. To address the visual disabilities due to
      DR, screening of all diabetics is suggested for early detection. The rationale
      and principles of DR screening are discussed. Based on the available evidence,
      the magnitude of DR in countries in the Eastern Mediterranean region (EMR) is
      presented. Public health strategies to control visual disabilities due to DR are
      discussed. These include generating evidence for planning, implementing standard
      operating procedures, periodic DR screening, focusing on primary prevention of
      DR, strengthening DR management, health information management and retrieval
      systems for DR, rehabilitating DR visually disabled, using low-cost technologies,
      adopting a comprehensive approach by integrating DR care into the existing health
      systems, health promotion/counseling, and involving the community. Although
      adopting the public health approach for DR has been accepted as a priority by
      member countries of EMR, challenges in implementation remain. These include
      limitations in the public health approach for DR compared to that for cataract,
      few skilled workers, poor health systems and lack of motivation in affecting
      health-related lifestyle changes in diabetics. Visual disabilities due to DR are
      likely to increase in the coming years. An organized public health approach must
      be adopted and all stakeholders must work together to control severe visual
      disabilities due to DR.

PMID- 22623856
TI  - Photodynamic therapy with verteporfin for corneal neovascularization.
AB  - PURPOSE: To investigate the efficacy of photodynamic therapy (PDT) with
      verteporfin for the treatment of patients with corneal neovascularization.
      MATERIALS AND METHODS: Retrospective interventional case series of 33 eyes of 32
      patients with stable corneal neovascularization who were refractory to
      conventional treatment and were treated with single photodynamic therapy with
      verteporfin (6 mg/m(2)) at King Khaled Eye Specialist Hospital, Riyadh, Saudi
      Arabia between January 1, 2007 and December 30, 2009. The mean age was 40.7 +/-
      19 years (range 16-76 years). The mean follow-up for all patients was 13.1 +/-
      5.5 months (range 6-24 months). The average amount of corneal neovascularization
      was 2.7 +/- 1.9 (1-10). Corneal neovascularization was deep in 19 (57.6%) eyes
      and superficial in 14 (42.4%) eyes. Preoperative and postoperative visual acuity
      and intraocular pressure, and clinical outcome of the treatment were assessed.
      Statistical analysis was performed to investigate the association to potential
      risk factors, to assess the change in data and determine the risks for failure. A
      P-value less than 0.05 was statistically significant. RESULTS: At the last follow
      up visit, 22 (66.7%) eyes showed a decrease in corneal neovascularization and
      evidence of vascular thrombosis. Complete vascular occlusion was achieved in 14
      (42.4%) eyes, partial occlusion was achieved in 8 (24.2%) eyes, and the vessels
      were patent in 11 (33.3%) eyes. The corneal neovascularization score and depth of
      the vessels were found to be significant risk factors for failure (P = 0.0001 and
      0.046, respectively). However, the diagnoses or causes of corneal
      neovascularisation were not statistically significant. No significant systemic or
      ocular complications associated with photodynamic therapy were observed.
      CONCLUSION: Photodynamic therapy with verteporfin was effective for the treatment
      of corneal neovascularization in the majority of the cases in this study.

PMID- 22623857
TI  - Xerophthalmia in a traditional Quran boarding school in Sudan.
AB  - PURPOSE: To determine the prevalence of xerophthalmia at a traditional boarding
      school where children do not receive a diet adequate in vitamin A. MATERIALS AND
      METHODS: A cross-sectional survey of 406 males residing in a Quranic traditional
      school was conducted using the World Health Organization xerophthalmia checklist.
      The association between the prevalence of night blindness and proportion of
      students staying at the school for 6 consecutive months and those eating solely
      at the school was investigated. The difference in age between children with night
      blindness and those without was investigated. Statistical significance was
      indicated by P<0.05. RESULTS: The prevalence of night blindness, conjunctival
      xerosis and Bitot's spots was 24%, 12.5% and 1%, respectively. None of the boys
      had corneal ulceration, corneal scars and corneal xerosis. No significant
      association was observed between the differences in mean age and development of
      night blindness (P=0.657). There was a significant association between the
      duration of stay (cut-off of 6 months continuously) at the institute and the
      development of night blindness (P=0.023). There was no statistical significance
      between regularly eating at the maseed and outside the "maseed" and the
      development of night blindness (P=0.75). CONCLUSION: Children residing at a
      traditional school are vulnerable to developing xerophthalmia where the diet is
      inadequate in vitamin A. Institutional caregivers should be made aware of the
      importance of providing a balanced diet rich in vitamin A. Institutional
      caregivers should also be educated on the signs and symptoms of vitamin A
      deficiency for early detection of xerophthalmia.

PMID- 22623858
TI  - Central corneal thickness in Iranian congenital glaucoma patients.
AB  - PURPOSE: To compare central corneal thickness (CCT) in subjects with controlled
      primary congenital glaucoma (PCG) and nonglaucomatous subjects and to investigate
      the correlation between CCT and intraocular pressure (IOP) in the study
      population. MATERIALS AND METHODS: Twenty-three consecutive PCG cases with
      controlled IOP and no clinical evidence of corneal edema comprised the Study
      Group. There was an interval of at least 2 months between last intraocular
      surgery and inclusion in the study. Twenty-one subjects with strabismus or
      lacrimal drainage insufficiency who did not have glaucoma or any history of
      intraocular surgery or ocular trauma comprised the control group. The Control
      Group was age and sex-matched. Data from ultrasonic pachymetry and applanation
      tonometry were analyzed for differences between groups. Correlation of the study
      parameters was investigated. A P-value less than 0.05 was statistically
      significant. RESULTS: Data from both eyes of subjects in the Study Group and
      Control Group were included in the original analysis. Mean CCT was statistically
      significantly higher in the Study Group compared to the Control Group (589.42 +/-
      53.44 MUm vs. 556.14 +/- 30.51 MUm, respectively; P=0.001). There was a
      significant correlation between CCT and IOP (r=0.63; P<0.0001). Similar
      statistically significant outcomes were observed when only one eye per subject
      was used in a reanalysis of the data for the Study and Control Groups.
      CONCLUSION: Patients with PCG who had controlled IOP have statistically
      significantly thicker corneas than nonglaucomatous age and sex-matched subjects
      The thicker cornea could significantly alter IOP measurement with applanation
      tonometry. Pachymetry should be considered an essential part of the evaluation
      for PCG.

PMID- 22623859
TI  - Evaluation of sterile uveitis after iris-fixated phakic intraocular lens
      implantation.
AB  - PURPOSE: To evaluate the clinical features, and visual outcomes of sterile
      uveitis after iris-fixated phakic intraocular lens implantation (pIOLs) (Artisan
      Artiflex((r)) and Verisyse-Veriflex((r))). MATERIAL AND METHODS: In this
      retrospective non-comparative case series, the medical records of 117 eyes
      implanted with Artisan-Artiflex((r)) (Ophtec BV, Groningen, Netherlands) and
      Verisyse-Veriflex((r)) (AMO, Santa Ana, CA) iris claw phakic IOLs were analyzed
      for postimplantation sterile uveitis. The mean age of the 87 patients included in
      the study was 27.2+/-7.4 years. Of these patients, 56 (64.3%) were men and 31
      (35.6%) were women. Patient age, gender, IOL brand type, refractive error, optic
      diameter, unilateral vs bilateral implantation, and anterior chamber depth were
      analyzed. Features of uveitis, uncorrected and best corrected visual acuity (VA)
      at presentation and at follow-up visits were examined. The mean follow-up time
      was 14.6 months (range: 6-37 months). RESULTS: Clinically significant uveitis was
      observed in 12 of 117 eyes (10.3%) in a total of ten patients. Of these ten
      patients, four (40%) were women and six (60%) were men, and the mean age was
      25.1+/-5.3 years (range: 18-36 years). Among those with bilateral implantation,
      6.9% of patients developed bilateral uveitis, while 13.8% (4 of the 29 implanted
      bilaterally) developed unilateral uveitis. Foldable pIOL implantation was the
      only variable associated with the development of uveitis (P=.03). CONCLUSION:
      Although the prognosis is usually benign, sterile uveitis occurred in 10.3% of
      patients after iris-fixated pIOL implantation. The implantation of a foldable
      pIOL was the only variable associated with sterile uveitis. Appropriate medical
      management can be effective treatment, without the need for pIOL replacement.

PMID- 22623860
TI  - Macular retinal and nerve fiber layer thickness in early glaucoma: clinical
      correlations.
AB  - PURPOSE: Previous studies have evaluated macular retinal thickness (RT) and nerve
      fiber layer thickness (RNFLT) changes in early glaucoma using elaborate optical
      coherence tomography (OCT) scanning protocols. MATERIALS AND METHODS: This study
      examines RT and RNFLT using standard scanning protocols in early glaucoma. In
      this prospective, nonrandomized case series, 95 eyes of 95 patients were
      evaluated, including 29 nonglaucomatous subjects (control group), 34 glaucoma
      suspects, and 32 early manifest glaucoma patients. RT and RNFLT were measured
      using scanning fast macular thickness map and Fast RNFLT (3.4) protocols on a
      1.70 mm radius around the macular center (respectively) in all four quadrants.
      The fast RNFLT (3.4) protocol was transposed on the macula from the peri
      papillary area. Data were statistically analyzed for differences between groups,
      and for correlations between parameters. P<0.5 was statistically significant.
      RESULTS: Both early manifest glaucoma patients and glaucoma suspects had
      significantly lower RT than controls in all quadrants. RNFLT differences in all
      quadrants were not statistically significant (P>0.05). RT was significantly
      inversely correlated with axial length in early manifest glaucoma patients and
      glaucoma suspects but not in controls. CONCLUSIONS: The finding that RT was
      significantly lower in early manifest glaucoma patients and glaucoma suspects
      indicates that the transposition of the OCT fast RNFL thickness (3.4) protocol
      from the peri-papillary area to the peri-macular area can be used for early
      glaucoma diagnosis. Intraretinal changes in early glaucoma, likely precede nerve
      fiber changes.

PMID- 22623861
TI  - Comparison of Humphrey Matrix frequency doubling technology to standard automated
      perimetry in neuro-ophthalmic disease.
AB  - PURPOSE: We compared Humphrey Matrix FDT 30-2 (FDT) and Humphrey Visual Field
      Analyzer 30-2 SITA standard (SAP) in the assessment of anterior (optic nerve or
      chiasm) and posterior (retro-chiasmal) afferent visual pathway defects. MATERIALS
      AND METHODS: In this retrospective comparative study, the charts of 37 patients
      (16 males, range 13-84 years, mean 72.1), with neuro-ophthalmic visual field
      defects who were tested with both FDT and SAP, were reviewed. Two masked graders
      assessed the concordance and extent of field defects between the perimeters. The
      mean concordance between anterior and posterior disease was compared using the
      Wilcoxon rank sum test. The mean deviation (MD) and pattern standard deviation
      (PSD) of each perimeter were correlated with the Spearman coefficient. RESULTS:
      Twenty-eight patients had anterior and nine had posterior disease. Most had a
      fair or good concordance (89.3% anterior, 88.9% posterior). When comparing
      anterior to posterior disease, the mean concordance of the defects of the two
      parameters was not statistically different (P = 0.94 and P = 0.61 for total
      deviation and pattern deviation, respectively). The MD and PSD between perimeters
      had a significant correlation. CONCLUSIONS: Our series, using 30-2 field
      analysis, demonstrates fair to good correlation between FDT and SAP in the
      majority of patients. In roughly 10% findings between FDT and SAP were
      discordant. This difference was similar for anterior and posterior disease.

PMID- 22623862
TI  - Office-based slit-lamp needle revision with adjunctive mitomycin-C for late
      failed or encapsulated filtering blebs.
AB  - PURPOSE: The purpose of this study was to assess the results of bleb needling in
      glaucomatous patients with late failed filtering blebs. MATERIALS AND METHODS: A
      retrospective case series of 27 eyes of 27 patients was considered. All patients
      underwent needle bleb revision with adjuvant mitomycin-C performed at the slit
      lamp, during an office visit. Complete success was defined as postneedling
      intraocular pressure (IOP) <= 21 mmHg without any antiglaucoma medications and
      qualified success was IOP <= 21 mmHg with topical antiglaucoma medications.
      RESULTS: There were 12 eyes with encapsulated blebs and 15 eyes with flat blebs.
      The mean interval between index filtering surgery and bleb revision was 32.74 +/-
      15.36 months. Mean IOP was 25.07 +/- 4.80 mmHg before surgery and 19.66 +/- 4.97
      mmHg at last postoperative follow-up. The mean follow-up was 20.31 +/- 15.63
      months. Complete and qualified successes were 7.4% and 51.9%, respectively.
      Cumulative rates of success at 1, 2, 3, and 4 years were 76%, 65%, 49%, and 37%,
      respectively. The mean number of antiglaucoma medications was reduced from 3.15
      +/- 0.36 preoperatively to 2.33 +/- 1.21 postoperatively (P<0.001). CONCLUSION:
      Slit-lamp needle revision in office is a simple and effective method for treating
      late encapsulated or flat filtering blebs without significant complications even
      for late bleb failure.

PMID- 22623863
TI  - Can opposite clear corneal incisions have a role with post-laser in situ
      keratomileusis astigmatism?
AB  - PURPOSE: To evaluate the astigmatic correcting effect of paired opposite clear
      corneal incisions (OCCIs) on the steep axis in patients with residual astigmatism
      after laser in situ keratomileusis (LASIK)  MATERIALS AND METHODS: Thirty-one
      eyes of 24 patients with a mean age of 28.4 years +/-2.46 (range, 19-36 years)
      were recruited for the study. Inclusion criteria included residual astigmatism of
      >=1.5 diopter (D) after LASIK with inadequate residual stromal bed thickness that
      precluded ablation. The cohort was divided into two groups; group I (with
      astigmatism ranging from -1.5 D to -2.5 D) and group II (with astigmatism > -2.5
      D). The steep axis was marked prior to surgery. Paired three-step self-sealing
      opposite clear corneal incisions were performed 1-mm anterior to the limbus on
      the steep axis with 3.2-mm keratome for group I and 4.1 mm for group II. Patients
      were examined 1 day, 1 week, 1 month, 3 months and 6 months, postoperatively.
      Visual acuity, refraction, keratometry, and corneal topography were evaluated
      preoperatively and postoperatively. Analysis of the difference between groups was
      performed with the Student t-test. P<0.05 was considered statistically
      significant. RESULTS: The mean uncorrected visual acuity (UCVA) improved from
      0.35+/-0.13 (range, 0.1-0.6) to 0.78+/-0.19 (range, 0.5-1) in group I and from
      0.26+/-0.19 (range, 0.1-0.5) to 0.7+/-0.18 (range, 0.4-1) in group II. The
      increase in UCVA was statistically significant in both groups (P=0.001, both
      cases). The mean preoperative and postoperative keratometric astigmatism in group
      I was 2.0+/-0.48 D (range, 1.5-2.5 D) and 0.8+/-0.37 D (range, 0.1-1.4 D),
      respectively. The decrease in keratometric astigmatism was highly statistically
      significant in group II (P=0.001.). Mean surgically induced astigmatic reduction
      by vector analysis was 1.47+/-0.85 D and 2.21+/-0.97 D in groups I and II
      respectively. There were no incision-related complications. CONCLUSIONS: Paired
      OCCIs were predictable and effective in correcting post-LASIK astigmatism and
      required no extra surgical skill or expensive instruments. OCCIs are especially
      useful in eyes with insufficient corneal thickness for LASIK retreatment.

PMID- 22623864
TI  - Inner and outer retinal volumetric and morphologic analysis of the macula with
      spectral domain optical coherence tomography in retinitis pigmentosa.
AB  - PURPOSE: To use spectral domain optical coherence tomography (OCT) to assess the
      features of the inner and outer layers of the macula in subjects with retinitis
      pigmentosa (RP). DESIGN: Prospective observational comparative study. MATERIALS
      AND METHODS: Subjects with RP with reduced central visual acuity and central
      macular thinning (RP group) underwent spectral domain OCT evaluation along with
      age-matched healthy control subjects (control group). Using the E-MM5 raster
      protocol, a 5 * 5 mm central macular cut was acquired with inner and outer
      macular volumes serving as the primary outcome measures. A structural analysis of
      the inner and outer retinal layers at the macula in the RP group was also
      performed using the HD cross-line protocol. RESULTS: The RP group comprised six
      eyes of six RP subjects and control group comprised six eyes of six control
      subjects. The outer macular volume was significantly lower (P<0.05) in the RP
      group (2.01+/-0.44 mm(3)) compared to the control group (4.68+/-0.16 mm(3)).
      There was no difference in the mean inner macular volume between the RP group
      (2.46+/-0.24 mm(3)) and the control group (2.55+/-0.22 mm(3)). No significant
      structural alteration was noted in the inner retinal layers of the RP group.
      There was no significant correlation (r = -0.04, P>0.05) between best-corrected
      visual acuity and outer macular volume in the RP group. CONCLUSIONS: Spectral
      domain OCT findings confirm that RP preferentially affects the outer retinal
      layers in the macula. Although the number of patients included in this study was
      small, it demonstrated relatively well-preserved volume and morphology of the
      inner retinal layers using spectral domain OCT.

PMID- 22623865
TI  - Ocular clinical profile of patients with pseudoexfoliation syndrome in a tertiary
      eye care center in South India.
AB  - PURPOSE: To study the clinical profile of pseudoexfoliation (PEX) syndrome in a
      hospital setting. MATERIALS AND METHODS: A case series of patients with PEX, with
      and without glaucoma attending the general ophthalmology clinic of a tertiary
      care center in South India. All patients underwent a complete ophthalmologic
      evaluation including recording diurnal variation of tension (DVT), gonioscopy and
      visual field assessment. RESULTS: The study cohort comprised 529 patients (752
      eyes). There were 296 (56%) females. The highest number of patients (261
      patients) was from the age group between 60 and 69 years. Of 752 eyes, 57.8% eyes
      had unilateral PEX and 72% had established PEX. Gonioscopy showed open angles in
      98.1% of eyes. Intraocular pressure (IOP) greater than 21 mmHg in at least 1 of 4
      measurements was recorded in 5.7% eyes. DVT was normal in 96.4% of unilateral PEX
      eyes, similar to fellow non-PEX eyes. Pseudoexfoliation glaucoma occurred in 1.9%
      of eyes and 4.7% of eyes were glaucoma suspects. There was no correlation between
      the stage of PEX and increased IOP. Mean central corneal thickness of PEX eyes
      was 522 +/- 27MU. Pupillary dilatation in 90.5% eyes with early PEX was >= 7 mm.
      CONCLUSIONS: A small percentage of PEX eyes had raised IOP, and the number of
      eyes with glaucomatous optic neuropathy was even lower. PEX eyes did not
      demonstrate wide fluctuations in IOP. No correlation was found between raised IOP
      and stage of PEX. There was good pupillary dilatation in early stage PEX eyes
      suggesting that all PEX eyes may not have poor pupillary dilatation and related
      complications.

PMID- 22623866
TI  - Pupil-sparing complete third nerve palsy from cryptogenic midbrain stroke in an
      otherwise-healthy young adult with patent foramen ovale.
AB  - Although pupil-sparing in acute unilateral complete third nerve palsy is often a
      sign of ischemic nerve injury, it is not specific for injury outside of the
      midbrain. This report documents acute pupil-sparing complete third nerve palsy in
      an otherwise healthy young adult with patent foramen ovale and associated atrial
      dilatation who suffered cryptogenic focal midbrain stroke, presumably from a
      paradoxical embolism. The patent foramen ovale was surgically closed. Over the
      next several months neurological recovery was complete except for diplopia and
      relatively comitant hypotropia, which responded well to conventional strabismus
      surgery.

PMID- 22623867
TI  - Multifocal cysticercosis with optical coherence tomography findings in a child.
AB  - We herein report a case with multifocal cysticercosis--sub-conjunctival
      cysticercus cyst, sub-retinal cysticercosis, and neurocysticercosis in a child.
      The optical coherence tomography (OCT) findings of the sub-retinal cysticercus
      cyst are reported. He was treated with anti-helminthic drugs and oral
      prednisolone followed by surgical removal of the sub-retinal cyst. He
      subsequently underwent silicone oil removal with lens aspiration and intraocular
      lens implantation maintaining stable vision.

PMID- 22623868
TI  - A case of cat-scratch disease with unusual ophthalmic manifestations.
AB  - We report a case of cat-scratch disease with unusual posterior segment
      manifestations. A 12-year-old healthy male presented with three weeks history of
      decreased visual acuity in the right eye. A significant history of cat exposure
      and elevated Bartonella titers were present. A large white-gray vascularized mass
      extending off the optic disk, an early stellate maculopathy, a plaque of
      choroiditis, an inferior serous retinal detachment involving the macula were
      present in the right eye. Sector papillitis and a focal area of chorioretinitis
      along the superotemporal arcade with associated retinal artery to vein
      anastomosis were present in the left eye. Bilateral optic nerve head involvement
      including peripapillary angiomatosis, retinal-retinal anastomosis and plaque
      choroiditis as ocular complications of cat-scratch disease have not been
      previously described to our knowledge and make this case noteworthy.

PMID- 22623869
TI  - Comparison of optical coherence tomography findings in a patient with central
      retinal artery occlusion in one eye and end-stage glaucoma in the fellow eye.
AB  - This case describes a patient with chronic central retinal artery occlusion in
      one eye and end-stage traumatic glaucoma in the fellow eye. Optical coherence
      tomography (OCT) of the macula of the chronic phase of central retinal artery
      occlusion of the right eye indicated loss of the normal foveal depression,
      extensive inner retinal atrophy, and marked retinal thinning. In contrast, scans
      of the left eye with end-stage glaucoma demonstrated an intact foveal depression
      and limited retinal thinning. The pattern of macular OCT findings in this patient
      illustrates distinguishing features between chronic central retinal artery
      occlusion and chronic optic neuropathy due to end-stage glaucoma.

PMID- 22623870
TI  - Concurrent macular corneal dystrophy and keratoconus.
AB  - A 21-year-old female presented with progressive bilateral visual loss for the
      past 8 years. The patient had no history of systemic disease, surgery or
      medications. Complete ophthalmologic examination and topography were performed.
      On ophthalmic examination, uncorrected visual acuity was counting fingers at 2.5
      m (20/50 with pinhole) in the right and left eyes. Both corneas appeared hazy on
      gross examination. On slit-lamp biomicroscopy, focal grayish-white opacities with
      indistinct borders were noted in the superficial and deep corneal stroma of both
      eyes. Both corneas were thin and bulging. Corneal topography showed a pattern
      consistent with keratoconus. The patient underwent penetrating keratoplasty
      (PKP). Histopathologic studies after PKP confirmed the diagnosis of macular
      corneal dystrophy and keratoconus in the same eye. The patient was clinically
      diagnosed as a case of concurrent macular dystrophy and keratoconus, which is a
      very rare presentation.

PMID- 22623871
TI  - Acute retinal necrosis after Boston type I keratoprosthesis.
AB  - A case report of a 68-year-old male who developed acute retinal necrosis (ARN)
      after Boston type I keratoprosthesis is presented. The procedure was performed
      for multiple graft failure secondary to herpetic keratitis. Clinical data
      including visual acuity, color fundus photography, fluorescein angiography,
      laboratory tests findings, and management are presented. After exclusion of other
      causes by laboratory workup, the patient was diagnosed with ARN most likely
      secondary to herpetic infection. Intravenous acyclovir and oral prednisolone were
      administered to the patient resulting in marked improvement in visual acuity and
      regression in the size of the retinitis. The patient eventually developed a soft
      eye and choroidal detachment with light perception vision. In patients with a
      history of herpetic keratitis or keratouveitis, it is highly advisable to
      maintain prophylactic systemic antiviral treatment before and after any ocular
      procedure such as the Boston keratoprosthesis.

PMID- 22623872
TI  - Rhino-orbito-cerebral mucormycosis in an immunocompetent patient: case report and
      review of literature.
AB  - Rhino-orbito-cerebral mucormycosis is a fungal infection that can be fatal
      especially in immunocompromised patients. It is extremely rare in immunocompetent
      individuals. We describe here an immunocompetent patient who survived rhino
      orbito-cerebral mucormycosis due to Saksenaea vasiformis, and provide a
      literature review of this rare entity.

PMID- 22623873
TI  - Bilateral transient pupil closure after iris supported intraocular lens
      implantation in a case with Marfan syndrome.
AB  - A 16-year-old woman presented with Marfan syndrome and bilateral ectopia lentis.
      The surgical treatment including removal of the crystalline lens and implantation
      of an iris-supported intraocular lens in both eyes at a week interval.
      Postoperatively, the biomicroscopic examination showed total pupil closure
      bilaterally. After the topical tropicamide treatment, the pupil returned to
      normal shape.

PMID- 22623875
TI  - Corneal endothelial cell density following cataract surgery in eyes with previous
      blunt trauma.

PMID- 22623874
TI  - Combination of intracameral and intrastromal voriconazole in the treatment of
      recalcitrant Acremonium fungal keratitis.
AB  - We present a report of a 28-year-old female with fungal keratitis due to
      Acremonium that was unresponsive to full medical therapy over 3 weeks. The
      patient was treated with superficial keratectomy, intrastromal and intracameral
      voriconazole injections. There was a marked clinical improvement beginning on day
      3 post-therapy that was sustained until the last follow-up at 6 months. This is
      the first case of fungal keratitis due to Acremonium treated by a combination of
      intrastromal and intracameral voriconazole. This cost-effective treatment
      modality proved to be significant in impeding the progression of this potentially
      blinding disease and improving visual prognosis.

PMID- 22623877
TI  - Targeting bladder tumor cells in voided urine of Chinese patients with FITC
      CSNRDARRC peptide ligand.
AB  - OBJECTIVE: To study the practicality of the FITC-CSNRDARRC peptide ligand
      (containing the Cys-Ser-Asn-Arg-Asp-Ala-Arg-Arg-Cys nonapeptide) in diagnosing
      and monitoring bladder tumors. MATERIALS AND METHODS: Between March 2011 and
      September 2011, 80 consecutive patients with radiographic abnormalities,
      localizing hematuria, other symptoms, or signs were studied using the FITC
      CSNRDARRC ligand, urinary cytology (UC), and fluorescence in situ hybridization
      (FISH). The sensitivity and specificity of these three technologies were
      determined and compared. Cystoscopy and tissue biopsy were taken as the "gold
      standards" for bladder tumor diagnosis in this study. RESULTS: Twenty-nine out of
      80 patients were diagnosed with a bladder tumor via histopathological
      examination. The FITC-CSNRDARRC ligand was positive in 23 out of 29 bladder tumor
      patients and produced false negatives in six (20.69%) patients. The UC was
      positive in six out of 29 bladder tumor patients and produced false negatives in
      23 (79.31%) patients. The FISH was positive in 21 out of 29 bladder tumor
      patients and produced false negatives in eight (27.59%) patients. The overall
      sensitivity as verified by the FITC-CSNRDARRC ligand was much higher than in UC
      (79.31% versus 20.69%, P < 0.001) and was slightly higher than in FISH (79.31%
      versus 72.41%, P = 0.625). The sensitivity of FISH was significantly higher than
      that of UC (72.41% versus 20.69%, P < 0.001). Sensitivities of the FITC-CSNRDARRC
      ligand and UC by grade were 58.33% versus 8.3% for low-grade (LG) tumors (P =
      0.031) and 94.12% versus 29.41% for high-grade (HG) tumors (P = 0.003),
      respectively. The advantage was maintained in terms of the detection of invasive
      tumors between the FITC-CSNRDARRC ligand and UC (90.48% versus 23.81%, P = 0.001)
      as well as between FISH and UC (85.71% versus 23.81%, P = 0.003). The
      specificities for the FITC-CSNRDARRC ligand, UC, and FISH were 100%. CONCLUSION:
      Results show that the FITC-CSNRDARRC ligand is a promising noninvasive tool for
      diagnosis and surveillance in patients suspected of having a new bladder tumor.

PMID- 22623878
TI  - Parameterized Specification, Configuration and Execution of Data-Intensive
      Scientific Workflows.
AB  - Data analysis processes in scientific applications can be expressed as coarse
      grain workflows of complex data processing operations with data flow dependencies
      between them. Performance optimization of these workflows can be viewed as a
      search for a set of optimal values in a multidimensional parameter space
      consisting of input performance parameters to the applications that are known to
      affect their execution times. While some performance parameters such as grouping
      of workflow components and their mapping to machines do not affect the accuracy
      of the analysis, others may dictate trading the output quality of individual
      components (and of the whole workflow) for performance. This paper describes an
      integrated framework which is capable of supporting performance optimizations
      along multiple such parameters. Using two real-world applications in the spatial,
      multidimensional data analysis domain, we present an experimental evaluation of
      the proposed framework.

PMID- 22623879
TI  - A comparative study of substance use before and after establishing HIV infection
      status among people living with HIV/AIDS.
AB  - OBJECTIVE: To determine if significant differences exist in substance use among
      people living with HIV/AIDS (PLWHA) before and after establishing their HIV
      infection status.  METHOD: The study participants are HIV positive clients of a
      community based HIV/AIDS outreach facility located in Montgomery, Alabama. The
      questionnaire includes demographics, substance use and risky sexual behaviors
      pertaining to HIV transmission. Each participant completed an anonymous
      questionnaire. A total of 341 questionnaires were distributed and 326 were fully
      completed and returned, representing a response rate of 96%.  RESULTS: Findings
      revealed a statistically significant difference in alcohol consumption before sex
      among PLWHA before and after establishing their HIV infection status (p = .001).
      No significant differences were observed among participants who reported as
      having used drugs intravenously (p = .89), and among those sharing the same
      syringe/needle with another person (p = .87) before and after establishing their
      HIV infection status.  CONCLUSION: There is continued substance use and alcohol
      consumption before sex among PLWHA after establishing their HIV status despite
      clear evidence of such risky behaviors that could lead to an increase in exposure
      to HIV.

PMID- 22623880
TI  - Insomnia in pregnancy and factors related to insomnia.
AB  - This study aims to investigate insomnia experienced by pregnant women and factors
      associated with it. This study was designed as hospital-based, descriptive, and
      cross-sectional research. The participants were 486 people chosen with
      nonprobability random sampling method. The data were collected through Women's
      Health Initiative Insomnia Rating Scale, Beck Depression Inventory, and Interview
      Form. Insomnia prevalence in women participating in this study was found 52.2%.
      The results of logistic regression analysis showed that the risk of insomnia was
      2.03 times higher for those in the third trimester than those in the first and
      second trimesters, 2.19 times higher for those 20 years old and over than younger
      ones, and 2.63 times higher for those who had depression syndrome than those who
      did not. Insomnia in pregnant women who participated in this study was found to
      be at high rates.

PMID- 22623882
TI  - Landfill leachate toxicity removal in combined treatment with municipal
      wastewater.
AB  - Combined treatment of landfill leachate and municipal wastewater was performed in
      order to investigate the changes of leachate toxicity during biological
      treatment. Three laboratory A2O lab-scale reactors were operating under the same
      parameters (Q-8.5-10 L/d; HRT-1.4-1.6 d; MLSS 1.6-2.5 g/L) except for the
      influent characteristic and load. The influent of reactor I consisted of
      municipal wastewater amended with leachate from postclosure landfill; influent of
      reactor II consisted of leachate collected from transient landfill and municipal
      wastewater; reactor III served as a control and its influent consisted of
      municipal wastewater only. Toxicity of raw and treated wastewater was determinted
      by four acute toxicity tests with Daphnia magna, Thamnocephalus platyurus, Vibrio
      fischeri, and Raphidocelis subcapitata. Landfill leachate increased initial
      toxicity of wastewater. During biological treatment, significant decline of acute
      toxicity was observed, but still mixture of leachate and wastewater was harmful
      to all tested organisms.

PMID- 22623881
TI  - Microvascular guidance: a challenge to support the development of vascularised
      tissue engineering construct.
AB  - The guidance of endothelial cell organization into a capillary network has been a
      long-standing challenge in tissue engineering. Some research efforts have been
      made to develop methods to promote capillary networks inside engineered tissue
      constructs. Capillary and vascular networks that would mimic blood microvessel
      function can be used to subsequently facilitate oxygen and nutrient transfer as
      well as waste removal. Vascularization of engineering tissue construct is one of
      the most favorable strategies to overpass nutrient and oxygen supply limitation,
      which is often the major hurdle in developing thick and complex tissue and
      artificial organ. This paper addresses recent advances and future challenges in
      developing three-dimensional culture systems to promote tissue construct
      vascularization allowing mimicking blood microvessel development and function
      encountered in vivo. Bioreactors systems that have been used to create fully
      vascularized functional tissue constructs will also be outlined.

PMID- 22623883
TI  - Evaluation of the cytotoxicity of Satureja spicigera and its main compounds.
AB  - Satureja spicigera (Lamiaceae) grows wildly in Northwest of Iran. In this study,
      bioassay-guided isolation and identification of the main compounds has been
      reported using various chromatographic methods and comparison of their spectral
      data with those reported in the literature. Brine shrimp lethality and four
      cancerous cell lines HT29/219, Caco(2), NIH-3T3, and T47D were used for
      cytotoxicity evaluations. From the aerial parts of S. spicigera, nine known
      compounds including two flavanones, 5,7,3',5'-tetrahydroxy flavanone (8) and 5,4'
      dihydroxy-3'-methoxyflavanone-7-(6''-O-alpha-L-rhamnopyranosyl)-beta-D
      glucopyranoside (9), one dihydrochalcone, nubigenol (7), together with
      thymoquinone (1), thymol (2), carvacrol (3), beta-sitosterol (4), ursolic acid
      (5) and oleanolic acid (6) were identified. Among the isolated chalcone and
      flavanones, compound 8 was effective against Artemia salina larva (LC(50)= 2
      MUg/mL) and only the compound 9 demonstrated IC(50) value of 98.7 MUg/mL on the
      T47D (human, breast, ductal carcinoma). Other compounds did not show significant
      inhibition of the cell growth.

PMID- 22623884
TI  - Apply Woods model in the predictions of ambient air particles and metallic
      elements (Mn, Fe, Zn, Cr, and Cu) at industrial, suburban/coastal, and
      residential sampling sites.
AB  - The main purpose for this study was to monitor ambient air particles and metallic
      elements (Mn, Fe, Zn, Cr, and Cu) in total suspended particulates (TSPs)
      concentration, dry deposition at three characteristic sampling sites of central
      Taiwan. Additionally, the calculated/measured dry deposition flux ratios of
      ambient air particles and metallic elements were calculated with Woods models at
      these three characteristic sampling sites during years of 2009-2010. As for
      ambient air particles, the results indicated that the Woods model generated the
      most accurate dry deposition prediction results when particle size was 18 MUm in
      this study. The results also indicated that the Woods model exhibited better dry
      deposition prediction performance when the particle size was greater than 10 MUm
      for the ambient air metallic elements in this study. Finally, as for Quan-xing
      sampling site, the main sources were many industrial factories under process
      around these regions and were severely polluted areas. In addition, the highest
      average dry deposition for Mn, Fe, Zn, and Cu species occurred at Bei-shi
      sampling site, and the main sources were the nearby science park, fossil fuel
      combustion, and Taichung thermal power plant (TTPP). Additionally, as for He-mei
      sampling site, the main sources were subjected to traffic mobile emissions.

PMID- 22623885
TI  - L-arginine intake effect on adenine nucleotide metabolism in rat parenchymal and
      reproductive tissues.
AB  - L-arginine is conditionally essetcial amino acid, required for normal cell
      growth, protein synthesis, ammonia detoxification, tissue growth and general
      performance, proposed in the treatment of men sterility and prevention of male
      impotence. The aim of the present paper was to estimate the activity of the
      enzymes of adenine nucleotide metabolism: 5'-nucleotidase (5'-NU), adenosine
      deaminase (ADA), AMP deaminase, and xanthine oxidase (XO), during dietary intake
      of L-arginine for a period of four weeks of male Wistar rats. Adenosine
      concentration in tissues is maintained by the relative activities of the
      adenosine-producing enzyme, 5'-NU and the adenosine-degrading enzyme-ADA
      adenosine deaminase. Dietary L-arginine intake directed adenine nucleotide
      metabolism in liver, kidney, and testis tissue toward the activation of adenosine
      production, by increased 5'-NU activity and decreased ADA activity. Stimulation
      of adenosine accumulation could be of importance in mediating arginine
      antiatherosclerotic, vasoactive, immunomodulatory, and antioxidant effects.
      Assuming that the XO activity reflects the rate of purine catabolism in the cell,
      while the activity of AMP deaminase is of importance in ATP regeneration, reduced
      activity of XO, together with the increased AMP-deaminase activity, may suggest
      that adenine nucleotides are presumably directed to the ATP regenerating process
      during dietary L-arginine intake.

PMID- 22623886
TI  - Determination of mould and aflatoxin contamination in tarhana, a Turkish
      fermented food.
AB  - Tarhana is a popular traditional Turkish cereal-based fermented food product
      mainly produced at home or at home-scale level. Some certain mould species can
      grow even at low moisture and pH values and produce aflatoxins in food. This
      study was conducted to determine aflatoksin levels in tarhana. For this purpose,
      a total of 138 tarhana powder samples were collected from bazaars in Istanbul and
      analyzed for aflatoxins, mould contamination, and some physico-chemical
      parameters. As a result, 32 out of 138 tarhana samples (23.2%) were found to be
      contaminated with aflatoxins in the range of 0.7-16.8 MUg/kg, whereas 29 samples
      contained Aflatoxin B1 (AFB1) ranging from 0.2-13.2 MUg/kg. All samples (100%)
      contaminated with moulds in the range of 1.4 * 10(1) -5.8 * 10(7)cfu/g. The
      average pH, moisture and a(w) results were detected as 3.82, 12.71%, and 0.695,
      respectively.

PMID- 22623887
TI  - Fluorescence-based rapid detection of microbiological contaminants in water
      samples.
AB  - Microbiological contamination of process waters is a current issue for
      pharmaceutical industries. Traditional methods require several days to obtain
      results; therefore, rapid microbiological methods are widely requested to shorten
      time-to-result. Milliflex Quantum was developed for the rapid detection and
      enumeration of microorganisms in filterable samples. It combines membrane
      filtration to universal fluorescent staining of viable microorganisms. This new
      alternative method was validated using European and United States Pharmacopeia
      definitions, with sterile water and/or sterile water artificially contaminated
      with microorganisms. The Milliflex Quantum method was demonstrated to be
      reliable, robust, specific, accurate, and linear over the whole range of assays
      following these guidelines. The Milliflex Quantum system was challenged to detect
      natural contaminants in different types of pharmaceutical purified process
      waters. Milliflex Quantum was demonstrated to detect accurately contaminants 3-
      to 7-fold faster than traditional membrane filtration method. The staining
      procedure is nondestructive allowing downstream identification following a
      positive result. The Milliflex Quantum offers a fast, sensitive, and robust
      alternative to the compendial membrane filtration method.

PMID- 22623888
TI  - A Chinese chan-based mind-body intervention improves sleep on patients with
      depression: a randomized controlled trial.
AB  - Sleep disturbance is a common problem associated with depression, and cognitive
      behavioral therapy (CBT) is a more common behavioral intervention for sleep
      problems. The present study compares the effect of a newly developed Chinese Chan
      based intervention, namely Dejian mind-body intervention (DMBI), with the CBT on
      improving sleep problems of patients with depression. Seventy-five participants
      diagnosed with major depressive disorder were randomly assigned to receive 10
      weekly sessions of CBT or DMBI, or placed on a waitlist. Measurements included
      ratings by psychiatrists who were blinded to the experimental design, and a
      standardized questionnaire on sleep quantity and quality was obtained before and
      after the 10-week intervention. Results indicated that both the CBT and DMBI
      groups demonstrated significantly reduced sleep onset latency and wake time after
      sleep onset (effect size range = 0.46-1.0, P <= 0.05) as compared to
      nonsignificant changes in the waitlist group (P > 0.1). Furthermore, the DMBI
      group, but not the CBT or waitlist groups, demonstrated significantly reduced
      psychiatrist ratings on overall sleep problems (effect size = 1.0, P = 0.00) and
      improved total sleep time (effect size = 0.8, P = 0.05) after treatment. The
      present findings suggest that a Chinese Chan-based mind-body intervention has
      positive effects on improving sleep in individuals with depression.

PMID- 22623889
TI  - Better outcomes in severe and morbid obese patients (BMI > 35 kg/m2) in primary
      Endo-Model rotating-hinge total knee arthroplasty.
AB  - The Endo-Model rotating-hinge prosthesis is preferably indicated as a primary
      implant in patients with advanced axial deviation of the lower limbs or unstable
      knees with severe bone defects. Outcomes were studied in 111 knees, operated in a
      three-year period; the mean followup was 28 months. Joint balance enhancement and
      limbs mechanical axis correction were achieved after surgery. There were 6 deep
      infections and 16 patients referred postoperative anterior knee pain. WOMAC index
      scores disaggregated by gender and BMI showed better outcomes in obese patients
      (specifically, those with a BMI of 35-40 kg/m(2)) and in men. Although the lack
      of a control group did not allow definite conclusions and despite a nonnegligible
      complication rate, our results reveal that the Endo-Model total knee arthroplasty
      can be a useful tool to deal with severe and morbid obese patients affected of
      severe gonarthrosis associated with marked axial deviations, ligament
      instability, or bone defects.

PMID- 22623890
TI  - PTEN gene: a model for genetic diseases in dermatology.
AB  - PTEN gene is considered one of the most mutated tumor suppressor genes in human
      cancer, and it's likely to become the first one in the near future. Since 1997,
      its involvement in tumor suppression has smoothly increased, up to the current
      importance. Germline mutations of PTEN cause the PTEN hamartoma tumor syndrome
      (PHTS), which include the past-called Cowden, Bannayan-Riley-Ruvalcaba, Proteus,
      Proteus-like, and Lhermitte-Duclos syndromes. Somatic mutations of PTEN have been
      observed in glioblastoma, prostate cancer, and brest cancer cell lines, quoting
      only the first tissues where the involvement has been proven. The negative
      regulation of cell interactions with the extracellular matrix could be the way
      PTEN phosphatase acts as a tumor suppressor. PTEN gene plays an essential role in
      human development. A recent model sees PTEN function as a stepwise gradation,
      which can be impaired not only by heterozygous mutations and homozygous losses,
      but also by other molecular mechanisms, such as transcriptional regression,
      epigenetic silencing, regulation by microRNAs, posttranslational modification,
      and aberrant localization. The involvement of PTEN function in melanoma and
      multistage skin carcinogenesis, with its implication in cancer treatment, and the
      role of front office in diagnosing PHTS are the main reasons why the
      dermatologist should know about PTEN.

PMID- 22623891
TI  - Antimicrobial, anti-inflammatory, antiparasitic, and cytotoxic activities of
      Laennecia confusa.
AB  - The current paper investigated the potential benefit of the traditional Mexican
      medicinal plant Laennecia confusa (Cronquist) G. L. Nesom (Asteraceae). Fractions
      from the hexane, chloroform, methanol, and aqueous extracts were analyzed for
      antibacterial, antifungal, anti-inflammatory, and antiparasitic activities. The
      antimicrobial activity of the extracts and fractions was assessed on bacterial
      and fungal strains, in addition to the protozoa Leishmania donovani, using a
      microdilution assay. The propensity of the plant's compounds to produce adverse
      effects on human health was also evaluated using propidium iodine to identify
      damage to human macrophages. The anti-inflammatory activity of the extracts and
      fractions was investigated by measuring the secretion of interleukin-6. Chemical
      analyses demonstrated the presence of flavonoids, cyanogenic and cardiotonic
      glycosides, saponins, sesquiterpene lactones, and triterpenes in the chloroform
      extract. A number of extracts and fractions show antibacterial activity. Of
      particular interest is antibacterial activity against Staphylococcus aureus and
      its relative methicillin-resistant strain, MRSA. Hexanic and chloroformic
      fractions also exhibit antifungal activity and two extracts and the fraction CE 2
      antiparasitic activity against Leishmania donovani. All bioactive extracts and
      fractions assayed were also found to be cytotoxic to macrophages. In addition,
      the hexane and methane extracts show anti-inflammatory activity by suppressing
      the secretion of interleukine-6.

PMID- 22623893
TI  - Resilience as a positive youth development construct: a conceptual review.
AB  - The concept of resilience is reviewed from a range of disciplinary perspectives
      in this paper. Both broad and narrow definitions of resilience are highlighted
      and a working definition of resilience is proposed to inform research, policy and
      practice. Different psychological, social and ecological protective factors,
      particularly competence, optimism, and bonding to family and cultural beliefs are
      highlighted. Theoretical relationships between resilience and positive youth
      development are examined with an attempt to erase misunderstandings. Finally, how
      schools can promote resilience among students is discussed.

PMID- 22623892
TI  - Monocytes do not transdifferentiate into proper osteoblasts.
AB  - Recent publications suggested that monocytes might be an attractive cell type to
      transdifferentiate into various cellular phenotypes. Aim was, therefore, to
      evaluate the potential of blood monocytes to transdifferentiate into osteoblasts.
      Monocytes isolated from peripheral blood were subjected to two previously
      published treatments to obtain unique, multipotent cell fractions, named
      programmable cells of monocytic origin (PCMOs) and monocyte-derived mesenchymal
      progenitor cells (MOMPs). Subsequently, MOMPs and PCMOs were treated with
      osteogenic differentiation medium (including either vitamin D or dexamethasone)
      for 14 days. Regarding a variety of surface markers, no differences between
      MOMPs, PCMOs, and primary monocytes could be detected. The treatment with
      osteogenic medium neither resulted in loss of hematopoietic markers nor in
      adoption of mesenchymal phenotype in all cell types. No significant effect was
      observed regarding the expression of osteogenic transcription factors, bone
      related genes, or production of mineralized matrix. Osteogenic medium resulted in
      activation of monocytes and appearance of osteoclasts. In conclusion, none of the
      investigated monocyte cell types showed any transdifferentiation characteristics
      under the tested circumstances. Based on our data, we rather see an activation
      and maturation of monocytes towards macrophages and osteoclasts.

PMID- 22623895
TI  - Ligand-based virtual screening using Bayesian inference network and reweighted
      fragments.
AB  - Many of the similarity-based virtual screening approaches assume that molecular
      fragments that are not related to the biological activity carry the same weight
      as the important ones. This was the reason that led to the use of Bayesian
      networks as an alternative to existing tools for similarity-based virtual
      screening. In our recent work, the retrieval performance of the Bayesian
      inference network (BIN) was observed to improve significantly when molecular
      fragments were reweighted using the relevance feedback information. In this
      paper, a set of active reference structures were used to reweight the fragments
      in the reference structure. In this approach, higher weights were assigned to
      those fragments that occur more frequently in the set of active reference
      structures while others were penalized. Simulated virtual screening experiments
      with MDL Drug Data Report datasets showed that the proposed approach
      significantly improved the retrieval effectiveness of ligand-based virtual
      screening, especially when the active molecules being sought had a high degree of
      structural heterogeneity.

PMID- 22623894
TI  - Hyperoxia reversibly alters oxygen consumption and metabolism.
AB  - AIM: Ventilation with pure oxygen (hyperoxic ventilation: HV) is thought to
      decrease whole body oxygen consumption (VO(2)). However, the validity and impact
      of this phenomenon remain ambiguous; until now, under hyperoxic conditions, VO(2)
      has only been determined by the reverse Fick principle, a method with inherent
      methodological problems. The goal of this study was to determine changes of
      VO(2), carbon dioxide production (VCO(2)), and the respiratory quotient (RQ)
      during normoxic and hyperoxic ventilation, using a metabolic monitor. METHODS:
      After providing signed informed consent and institutional acceptance, 14 healthy
      volunteers were asked to sequentially breathe room air, pure oxygen, and room air
      again. VO(2), VCO(2), RQ, and energy expenditure (EE) were determined by indirect
      calorimetry using a modified metabolic monitor during HV. RESULTS: HV reduced
      VO(2) from 3.4 (3.0/4.0) mL/kg/min to 2.8 (2.5/3.6) mL/kg/min (P < 0.05), whereas
      VCO(2) remained constant (3.0 [2.6/3.6] mL/kg/min versus 3.0 [2.6/3.5] mL/kg/min,
      n.s.). After onset of HV, RQ increased from 0.9 (0.8/0.9) to 1.1 (1.0/1.1). Most
      changes during HV were immediately reversed during subsequent normoxic
      ventilation. CONCLUSION: HV not only reduces VO(2), but also increases the
      respiratory quotient. This might be interpreted as an indicator of the
      substantial metabolic changes induced by HV. However, the impact of this
      phenomenon requires further study.

PMID- 22623897
TI  - Umbilical cord serum erythropoietin levels and maternal smoking in pregnancy.
AB  - OBJECTIVE: To evaluate the effect of maternal smoking during pregnancy on levels
      of umbilical cord erythropoietin. METHODS: Erythropoietin levels were measured in
      umbilical cord sera of 60 newborns who were delivered vaginally at term. There
      were 20 (33%) smoking and 40 (67%) nonsmoking mothers. RESULTS: Mean cord serum
      erythropoietin levels were significantly lower in the nonsmokers (nonsmokers, 24
      +/- 9 IU/L; smokers, 61 +/- 46 IU/L; P < .001). There was a significant positive
      correlation between the number of cigarettes smoked per day and cord serum
      erythropoietin levels (r, 0.58; P <= .05). CONCLUSIONS: Smoking during pregnancy
      is associated with increased levels of umbilical cord erythropoietin at birth.
      This may indicate a risk of fetal hypoxia and growth restriction. Education and
      encouragement of cessation of smoking during pregnancy are important to avoid
      associated fetal and maternal morbidity and mortality.

PMID- 22623896
TI  - SPECT and PET imaging of meningiomas.
AB  - Meningiomas arise from the meningothelial cells of the arachnoid membranes. They
      are the most common primary intracranial neoplasms and represent about 20% of all
      intracranial tumors. They are usually diagnosed after the third decade of life
      and they are more frequent in women than in men. According to the World Health
      Organization (WHO) criteria, meningiomas can be classified into grade I
      meningiomas, which are benign, grade II (atypical) and grade III (anaplastic)
      meningiomas, which have a much more aggressive clinical behaviour. Computed
      Tomography (CT) and Magnetic Resonance Imaging (MRI) are routinely used in the
      diagnostic workup of patients with meningiomas. Molecular Nuclear Medicine
      Imaging with Single Photon Emission Computed Tomography (SPECT) and Positron
      Emission Tomography (PET) could provide complementary information to CT and MRI.
      Various SPECT and PET tracers may provide information about cellular processes
      and biological characteristics of meningiomas. Therefore, SPECT and PET imaging
      could be used for the preoperative noninvasive diagnosis and differential
      diagnosis of meningiomas, prediction of tumor grade and tumor recurrence,
      response to treatment, target volume delineation for radiation therapy planning,
      and distinction between residual or recurrent tumour from scar tissue.

PMID- 22623898
TI  - Bonding as a positive youth development construct: a conceptual review.
AB  - The concept of bonding as a positive youth development construct is reviewed in
      this paper. The goals are fourfold. First, theoretical perspectives of bonding
      are delineated. Secondly, the relationships among bonding to caregivers, friends,
      romantic partners, as well as teachers, and adolescents' positive developmental
      outcomes are reviewed. Thirdly, with theoretical and empirical support, a
      discussion on how to promote bonding among adolescents is offered. Finally, a
      critical review on the cultural issues of bonding is provided.

PMID- 22623899
TI  - Crop row detection in maize fields inspired on the human visual perception.
AB  - This paper proposes a new method, oriented to image real-time processing, for
      identifying crop rows in maize fields in the images. The vision system is
      designed to be installed onboard a mobile agricultural vehicle, that is,
      submitted to gyros, vibrations, and undesired movements. The images are captured
      under image perspective, being affected by the above undesired effects. The image
      processing consists of two main processes: image segmentation and crop row
      detection. The first one applies a threshold to separate green plants or pixels
      (crops and weeds) from the rest (soil, stones, and others). It is based on a
      fuzzy clustering process, which allows obtaining the threshold to be applied
      during the normal operation process. The crop row detection applies a method
      based on image perspective projection that searches for maximum accumulation of
      segmented green pixels along straight alignments. They determine the expected
      crop lines in the images. The method is robust enough to work under the above
      mentioned undesired effects. It is favorably compared against the well-tested
      Hough transformation for line detection.

PMID- 22623901
TI  - Biosynthesis of indole-3-acetic acid by new Klebsiella oxytoca free and
      immobilized cells on inorganic matrices.
AB  - While many natural and synthetic compounds exhibit auxin-like activity in
      bioassays, indole-3-acetic acid (IAA) is recognized as the key auxin in most
      plants. IAA has been implicated in almost all aspects of plant growth and
      development and a large array of bacteria have been reported to enhance plant
      growth. Cells of Klebsiella oxytoca isolated from the rhizosphere of Aspidosperma
      polyneuron and immobilized by adsorption on different inorganic matrices were
      used for IAA production. The matrices were prepared by the sol-gel method and the
      silica-titanium was the most suitable matrix for effective immobilization. In
      operational stability assays, IAA production was maintained after four cycles of
      production, obtaining 42.80 +/- 2.03 MUg mL(-1) of IAA in the third cycle, which
      corresponds to a 54% increase in production in relation to the first cycle,
      whereas free cells began losing activity after the first cycle. After 90 days of
      storage at 4 degrees C the immobilized cells showed the slight reduction of IAA
      production without significant loss of activity.

PMID- 22623900
TI  - Genetics and epigenetics of Parkinson's disease.
AB  - In 1997 a mutation in the a-synuclein (SNCA) gene was associated with familial
      autosomal dominant Parkinson's disease (PD). Since then, several loci (PARK1-15)
      and genes have been linked to familial forms of the disease. There is now
      sufficient evidence that six of the so far identified genes at PARK loci (a
      synuclein, leucine-rich repeat kinase 2, parkin, PTEN-induced putative kinase 1,
      DJ-1, and ATP13A2) cause inherited forms of typical PD or parkinsonian syndromes.
      Other genes at non-PARK loci (MAPT, SCA1, SCA2, spatacsin, POLG1) cause syndromes
      with parkinsonism as one of the symptoms. The majority of PD cases are however
      sporadic "idiopathic" forms, and the recent application of genome-wide screening
      revealed almost 20 genes that might contribute to disease risk. In addition,
      increasing evidence suggests that epigenetic mechanisms, such as DNA methylation,
      histone modifications, and small RNA-mediated mechanisms, could regulate the
      expression of PD-related genes.

PMID- 22623903
TI  - Synthesis of nanoscale TiO2 and study of the effect of their crystal structure on
      single cell response.
AB  - To study the effect of nanoscale titanium dioxide (TiO(2)) on cell responses, we
      synthesized four modifications of the TiO(2) (amorphous, anatase, brookite, and
      rutile) capable of keeping their physicochemical characteristics in a cell
      culture medium. The modifications of nanoscale TiO(2) were obtained by hydrolysis
      of TiCl(4) and Ti(i-OC(3)H(7))(4) (TIP) upon variation of the synthesis
      conditions; their textural, morphological, structural, and dispersion
      characteristics were examined by a set of physicochemical methods: XRD, BET,
      SAXS, DLS, AFM, SEM, and HR-TEM. The effect of synthesis conditions (nature of
      precursor, pH, temperature, and addition of a complexing agent) on the structural
      dispersion properties of TiO(2) nanoparticles was studied. The hydrolysis methods
      providing the preparation of amorphous, anatase, brookite, and rutile
      modifications of TiO(2) nanoparticles 3-5 nm in size were selected. Examination
      of different forms of TiO(2) nanoparticles interaction with MDCK cells by
      transmission electron microscopy of ultrathin sections revealed different cell
      responses after treatment with different crystalline modifications and amorphous
      form of TiO(2). The obtained results allowed us to conclude that direct contact
      of the nanoparticles with cell plasma membrane is the primary and critical step
      of their interaction and defines a subsequent response of the cell.

PMID- 22623904
TI  - Brain reorganization in patients with brachial plexus injury: a longitudinal
      functional MRI study.
AB  - The aim of this study is to assess plastic changes of the sensorimotor cortex
      (SMC) in patients with traumatic brachial plexus injury (BPI) using functional
      magnetic resonance imaging (fMRI). Twenty patients with traumatic BPI underwent
      fMRI using blood oxygen level-dependent technique with echo-planar imaging before
      the operation. Sixteen patients underwent their second fMRI at approximately one
      year after injury. The subjects performed two tasks: a flexion-extension task of
      the affected elbow and a task of the unaffected elbow. After activation, maps
      were generated, the number of significantly activated voxels in SMC contralateral
      to the elbow movement in the affected elbow task study (N(af)) and that in the
      unaffected task study (N(unaf)) were counted. An asymmetry index (AI) was
      calculated, where AI = (N(af) - N(unaf))/(N(af) + N(unaf)). Ten healthy
      volunteers were also included in this fMRI study. The AI of the first fMRI of the
      patients with BPI was significantly lower than that of the healthy subjects (P =
      0.035). The AI of the second fMRI significantly decreased compared with that of
      the first fMRI (P = 0.045). Brain reorganization associates with peripheral
      nervous changes after BPI and after operation for functional reconstruction.

PMID- 22623902
TI  - The Golgi in cell migration: regulation by signal transduction and its
      implications for cancer cell metastasis.
AB  - Migration and invasion are fundamental features of metastatic cancer cells. The
      Golgi apparatus, an organelle involved in posttranslational modification and
      sorting of proteins, is widely accepted to regulate directional cell migration.
      In addition, mounting evidence suggests that the Golgi is a hub for different
      signaling pathways. In this paper we will give an overview on how polarized
      secretion and microtubule nucleation at the Golgi regulate directional cell
      migration. We will review different signaling pathways that signal to and from
      the Golgi. Finally, we will discuss how these signaling pathways regulate the
      role of the Golgi in cell migration and invasion. We propose that by identifying
      regulators of the Golgi, we might be able to uncover unappreciated modulators of
      cell migration. Uncovering the regulatory network that orchestrates cell
      migration is of fundamental importance for the development of new therapeutic
      strategies against cancer cell metastasis.

PMID- 22623905
TI  - Development of ternary and quaternary catalysts for the electrooxidation of
      glycerol.
AB  - This work consisted in the preparation of platinum-based catalysts supported on
      carbon (Vulcan XC-72) and investigation of their physicochemical and
      electrochemical properties. Catalysts of the C/Pt-Ni-Sn-Me (Me = Ru or Ir) type
      were prepared by the Pechini method at temperature of 350 degrees C. Four
      different compositions were homemade: C/Pt(60)Sn(10)Ni(30),
      C/Pt(60)Sn(10)Ni(20)Ru(10), C/Pt(60)Sn(10)Ni(10)Ru(20), and
      C/Pt(60)Sn(10)Ni(10)Ir(20). These catalysts were electrochemically and physically
      characterized by cyclic voltammetry (CV), chronoamperometry (CA) in the presence
      of glycerol 1.0 mol dm(-3), X-ray diffraction (XRD), and high-resolution
      transmission electron microscopy (HRTEM). XRD results showed the main peaks of
      face-centered cubic Pt. The particle sizes obtained from XRD and HRTEM
      experiments were close to values ranging from 3 to 8.5 nm. The CV results
      indicate behavior typical of Pt-based catalysts in acid medium. The CV and CA
      data reveal that quaternary catalysts present the highest current density for the
      electrooxidation of glycerol.

PMID- 22623906
TI  - Energy requirement and food intake behaviour in young adult intact male cats with
      and without predisposition to overweight.
AB  - Obesity is a common problem in cats. In the experimental cat family of the
      institute of animal nutrition besides a "normal" lean phenotype, cats with
      predisposition to an overweight phenotype are present. To investigate energy
      requirements and food intake behaviour of intact male cats of different
      phenotypes, six "normal" lean cats (GL) and six cats disposed to overweight (GO)
      were used. At the beginning of the experiment, all cats had an ideal body
      condition score of 5. To reach this the GO cats had to pass a weight-loss
      program. Energy requirements of the cats were determined using respiration
      chambers, whereas the amount and frequency of food intake was measured with a
      feeding station recording the data automatically. Energy requirement at weight
      constancy of the GO cats was even on fat-free mass (FFM) significantly (P = 0.02)
      lower (162.6 kJ/kg FFM/d) than that of the "normal" lean cats (246 kJ/kg FFM/d).
      The GO cats also showed a higher food intake 34.5 +/- 1.5 g dry matter/kg body
      weight(0.67) compared to the GL cats (24.0 +/- 2.1 g dry matter/kg body
      weight(0.67))(P = 0.001). In conclusion quantifiable differences in food intake
      and behaviour in cats predisposed to overweight compared to "normal" lean cats
      were found.

PMID- 22623907
TI  - Removal of triphenylmethane dyes by bacterial consortium.
AB  - A new consortium of four bacterial isolates (Agrobacterium radiobacter; Bacillus
      spp.; Sphingomonas paucimobilis, and Aeromonas hydrophila)-(CM-4) was used to
      degrade and to decolorize triphenylmethane dyes. All bacteria were isolated from
      activated sludge extracted from a wastewater treatment station of a dyeing
      industry plant. Individual bacterial isolates exhibited a remarkable color
      removal capability against crystal violet (50 mg/L) and malachite green (50 mg/L)
      dyes within 24 h. Interestingly, the microbial consortium CM-4 shows a high
      decolorizing percentage for crystal violet and malachite green, respectively, 91%
      and 99% within 2 h. The rate of chemical oxygen demand (COD) removal increases
      after 24 h, reaching 61.5% and 84.2% for crystal violet and malachite green,
      respectively. UV-Visible absorption spectra, FTIR analysis and the inspection of
      bacterial cells growth indicated that color removal by the CM-4 was due to
      biodegradation. Evaluation of mutagenicity by using Salmonella typhimurium test
      strains, TA98 and TA100 studies revealed that the degradation of crystal violet
      and malachite green by CM-4 did not lead to mutagenic products. Altogether, these
      results demonstrated the usefulness of the bacterial consortium in the treatment
      of the textile dyes.

PMID- 22623908
TI  - Study of the activity of 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2
      one against Schistosomiasis mansoni in mice.
AB  - Previous studies conducted with the imidazolidinic derivative 3-benzyl-5-(4
      chloro-arylazo)-4-thioxo-imidazolidin-2-one (LPSF-PT05) show outstanding activity
      against adult Schistosoma mansoni worms in vitro. In the first phase of this
      study, S. mansoni-infected mice were treated, orally, with 100 mg/Kg of the LPSF
      PT05 in three formulations: Tween 80 and saline solution, oil/water (70 : 30)
      emulsion, and solid dispersion with polyethylene glycol (PEG). In the second
      phase, three other doses of the LPSF-PT05 in PEG were tested: 3, 10, 30 mg/kg.
      These treatment regimens significantly reduced the number of recovered worms due
      to increases in the solubility of the compound in this formulation; the greatest
      reduction (70.5%) was observed at the dose of 100 mg/kg. There was no changes in
      the pattern of mature egg compared to immature eggs; however there was a
      significant increase in the number of dead eggs. Histopathological analysis of
      liver tissue showed changes in morphological aspects of the hepatic parenchyma
      with decrease exudative-productive hepatic granuloma stages, although we found no
      significant differences in IFN-gamma, IL-4, IL-10, or NO production in response
      to the specific antigen SEA. The results show the derivative LPSF-PT05 to be a
      potential candidate in the etiological treatment of schistosomiasis with a
      possible dampening effect of the granulomatous process.

PMID- 22623910
TI  - A survey on prevalence and pathological findings of gallstones in Lori-Bakhtiari
      sheep in Iran.
AB  - In a survey of 430 Lori-Bakhtiari sheep at a slaughterhouse in Iran, gallstones
      were found in the gallbladder of 7 sheep (1.6%). Biliary calculi were more
      frequent in adult and female sheep (P < 0.05). Chemical analysis of the
      gallstones revealed 6 sheep with pigment (bilirubin) stones and 1 sheep with
      cholesterol stones. Chemical composition of bile in these sheep was evaluated.
      Bacteriologic analysis of the bile in the affected sheep revealed bacteria
      (Streptococcus spp., Klebsiella spp., Escherichia coli, and Salmonella spp.) in 5
      sheep. Microscopic examination of gallbladders revealed focal calcification,
      cystic glands, necrosis and atrophy of mucosal layer, edema, diffuse and focal
      infiltration of lymphocytes in submucosal layer, and hypertrophy of smooth
      muscles in sheep with gallstones. It was concluded that the prevalence of both
      types of gallstones in Lori-Bakhtiari sheep is low. Cholelithiasis can cause
      chronic inflammation of the gallbladder, but it is not likely to become
      clinically significant.

PMID- 22623909
TI  - Fluorescence correlation spectroscopy in drug discovery: study of Alexa532
      endothelin 1 binding to the endothelin ETA receptor to describe the
      pharmacological profile of natural products.
AB  - Fluorescence correlation spectroscopy and the newly synthesized Alexa532-ET1 were
      used to study the dynamics of the endothelin ET(A) receptor-ligand complex alone
      and under the influence of a semisynthetic selective antagonist and a fungal
      extract on living A10 cells. Dose-dependent increase of inositol phosphate
      production was seen for Alexa532-ET1, and its binding was reduced to 8% by the
      selective endothelin ET(A) antagonist BQ-123, confirming the specific binding of
      Alexa532-ET1 to the endothelin ET(A) receptor. Two different lateral mobilities
      of the receptor-ligand complexes within the cell membrane were found allowing the
      discrimination of different states for this complex. BQ-123 showed a strong
      binding affinity to the "inactive" receptor state characterized by the slow
      diffusion time constant. A similar effect was observed for the fungal extract,
      which completely displaced Alexa532-ET1 from its binding to the "inactive"
      receptor state. These findings suggest that both BQ-123 and the fungal extract
      act as inverse agonists.

PMID- 22623911
TI  - Tautomerism in 11-hydroxyaklavinone: a DFT study.
AB  - The antharquinone-based chromophore of 11-hydroxyaklavinone is present in the
      structure of an anticancer agent, daunomycin. On the other hand, aklavinone is
      the parent aglycone of certain anthracycline antibiotics that possess anti-cancer
      activity too. The structures of aklavinone and its 11-hydroxy derivative have
      many -OH groups, and two keto groups which may take place in certain tautomeric
      equilibria. Of these tautomeric forms, presently the one involving the
      anthraquinone based tautomers of 11-hydroxyaklavinone has been investigated
      quantum chemically in the framework of the density functional theory at the
      levels of RB3LYP/6-31G(d) and RB3LYP/6-31G(d,p).

PMID- 22623912
TI  - Cortical development of AMPA receptor trafficking proteins.
AB  - AMPA-receptor trafficking plays a central role in excitatory plasticity,
      especially during development. Changes in the number of AMPA receptors and time
      spent at the synaptic surface are important factors of plasticity that directly
      affect long-term potentiation (LTP), long-term depression (LTD), synaptic
      scaling, and the excitatory-inhibitory (E/I) balance in the developing cortex.
      Experience-dependent changes in synaptic strength in visual cortex (V1) use a
      molecularly distinct AMPA trafficking pathway that includes the GluA2 subunit. We
      studied developmental changes in AMPA receptor trafficking proteins by
      quantifying expression of GluA2, pGluA2 (GluA2serine880), GRIP1, and PICK1 in rat
      visual and frontal cortex. We used Western Blot analysis of synaptoneurosome
      preparations of rat visual and frontal cortex from animals ranging in age from P0
      to P105. GluA2 and pGluA2 followed different developmental trajectories in visual
      and frontal cortex, with a brief period of over expression in frontal cortex. The
      over expression of GluA2 and pGluA2 in immature frontal cortex raises the
      possibility that there may be a period of GluA2-dependent vulnerability in
      frontal cortex that is not found in V1. In contrast, GRIP1 and PICK1 had the same
      developmental trajectories and were expressed very early in development of both
      cortical areas. This suggests that the AMPA-interacting proteins are available to
      begin trafficking receptors as soon as GluA2-containing receptors are expressed.
      Finally, we used all four proteins to analyze the surface-to-internalization
      balance and found that this balance was roughly equal across both cortical
      regions, and throughout development. Our finding of an exquisite surface-to
      internalization balance highlights that these AMPA receptor trafficking proteins
      function as a tightly controlled system in the developing cortex.

PMID- 22623913
TI  - Neurogliaform and Ivy Cells: A Major Family of nNOS Expressing GABAergic Neurons.
AB  - Neurogliaform and Ivy cells are members of an abundant family of neuronal nitric
      oxide synthase (nNOS) expressing GABAergic interneurons found in diverse brain
      regions. These cells have a defining dense local axonal plexus, and display
      unique synaptic properties including a biphasic postsynaptic response with both a
      slow GABA(A) component and a GABA(B) component following even a single action
      potential. The type of transmission displayed by these cells has been termed
      "volume transmission," distinct from both tonic and classical synaptic
      transmission. Electrical connections are also notable in that, unlike other
      GABAergic cell types, neurogliaform family cells will form gap junctions not only
      with other neurogliaform cells, but also with non-neurogliaform family GABAergic
      cells. In this review, we focus on neurogliaform and Ivy cells throughout the
      hippocampal formation, where recent studies highlight their role in feedforward
      inhibition, uncover their ability to display a phenomenon called persistent
      firing, and reveal their modulation by opioids. The unique properties of this
      family of cells, their abundance, rich connectivity, and modulation by clinically
      relevant drugs make them an attractive target for future studies in vivo during
      different behavioral and pharmacological conditions.

PMID- 22623914
TI  - Bidirectional gray matter changes after complex motor skill learning.
AB  - Long-term motor skill learning has been consistently shown to result in
      functional as well as structural changes in the adult human brain. However, the
      effect of short learning periods on brain structure is not well understood. In
      the present study, subjects performed a sequential pinch force task (SPFT) for 20
      min on 5 consecutive days. Changes in brain structure were evaluated with
      anatomical magnetic resonance imaging (MRI) scans acquired on the first and last
      day of motor skill learning. Behaviorally, the SPFT resulted in sequence-specific
      learning with the trained (right) hand. Structural gray matter (GM) alterations
      in left M1, right ventral premotor cortex (PMC) and right dorsolateral prefrontal
      cortex (DLPFC) correlated with performance improvements in the SPFT. More
      specifically we found that subjects with strong sequence-specific performance
      improvements in the SPFT also had larger increases in GM volume in the respective
      brain areas. On the other hand, subjects with small behavioral gains either
      showed no change or even a decrease in GM volume during the time course of
      learning. Furthermore, cerebellar GM volume before motor skill learning predicted
      (A) individual learning-related changes in the SPFT and (B) the amount of
      structural changes in left M1, right ventral PMC and DLPFC. In summary, we
      provide novel evidence that short-term motor skill learning is associated with
      learning-related structural brain alterations. Additionally, we showed that
      practicing a motor skill is not exclusively accompanied by increased GM volume.
      Instead, bidirectional structural alterations explained the variability of the
      individual learning success.

PMID- 22623915
TI  - Correlated components of ongoing EEG point to emotionally laden attention - a
      possible marker of engagement?
AB  - Recent evidence from functional magnetic resonance imaging suggests that cortical
      hemodynamic responses coincide in different subjects experiencing a common
      naturalistic stimulus. Here we utilize neural responses in the
      electroencephalogram (EEG) evoked by multiple presentations of short film clips
      to index brain states marked by high levels of correlation within and across
      subjects. We formulate a novel signal decomposition method which extracts
      maximally correlated signal components from multiple EEG records. The resulting
      components capture correlations down to a one-second time resolution, thus
      revealing that peak correlations of neural activity across viewings can occur in
      remarkable correspondence with arousing moments of the film. Moreover, a
      significant reduction in neural correlation occurs upon a second viewing of the
      film or when the narrative is disrupted by presenting its scenes scrambled in
      time. We also probe oscillatory brain activity during periods of heightened
      correlation, and observe during such times a significant increase in the theta
      band for a frontal component and reductions in the alpha and beta frequency bands
      for parietal and occipital components. Low-resolution EEG tomography of these
      components suggests that the correlated neural activity is consistent with
      sources in the cingulate and orbitofrontal cortices. Put together, these results
      suggest that the observed synchrony reflects attention- and emotion-modulated
      cortical processing which may be decoded with high temporal resolution by
      extracting maximally correlated components of neural activity.

PMID- 22623916
TI  - I think, therefore I am (unhappy).

PMID- 22623918
TI  - Ensemble modeling of cancer metabolism.
AB  - The metabolic behavior of cancer cells is adapted to meet their proliferative
      needs, with notable changes such as enhanced lactate secretion and glucose uptake
      rates. In this work, we use the Ensemble Modeling (EM) framework to gain insight
      and predict potential drug targets for tumor cells. EM generates a set of models
      which span the space of kinetic parameters that are constrained by
      thermodynamics. Perturbation data based on known targets are used to screen the
      entire ensemble of models to obtain a sub-set, which is increasingly predictive.
      EM allows for incorporation of regulatory information and captures the behavior
      of enzymatic reactions at the molecular level by representing reactions in the
      elementary reaction form. In this study, a metabolic network consisting of 58
      reactions is considered and accounts for glycolysis, the pentose phosphate
      pathway, lipid metabolism, amino acid metabolism, and includes allosteric
      regulation of key enzymes. Experimentally measured intracellular and
      extracellular metabolite concentrations are used for developing the ensemble of
      models along with information on established drug targets. The resulting models
      predicted transaldolase (TALA) and succinyl-CoA ligase (SUCOAS1m) to cause a
      significant reduction in growth rate when repressed, relative to currently known
      drug targets. Furthermore, the results suggest that the synergistic repression of
      transaldolase and glycine hydroxymethyltransferase (GHMT2r) will lead to a
      threefold decrease in growth rate compared to the repression of single enzyme
      targets.

PMID- 22623917
TI  - Increasing the clinical efficacy of NK and antibody-mediated cancer
      immunotherapy: potential predictors of successful clinical outcome based on
      observations in high-risk neuroblastoma.
AB  - Disease recurrence is frequent in high-risk neuroblastoma (NBL) patients even
      after multi-modality aggressive treatment [a combination of chemotherapy,
      surgical resection, local radiation therapy, autologous stem cell
      transplantation, and cis-retinoic acid (CRA)]. Recent clinical studies have
      explored the use of monoclonal antibodies (mAbs) that bind to disialoganglioside
      (GD(2)), highly expressed in NBL, as a means to enable immune effector cells to
      destroy NBL cells via antibody-dependent cell-mediated cytotoxicity (ADCC).
      Preclinical data indicate that ADCC can be more effective when appropriate
      effector cells are activated by cytokines. Clinical studies have pursued this by
      administering anti-GD(2) mAb in combination with ADCC-enhancing cytokines (IL2
      and GM-CSF), a regimen that has demonstrated improved cancer-free survival. More
      recently, early clinical studies have used a fusion protein that consists of the
      anti-GD(2) mAb directly linked to IL2, and anti-tumor responses were seen in the
      Phase II setting. Analyses of genes that code for receptors that influence ADCC
      activity and natural killer (NK) cell function [Fc receptor (FcR), killer
      immunoglublin-like receptor (KIR), and KIR-ligand (KIR-L)] suggest patients with
      anti-tumor activity are more likely to have certain genotype profiles. Further
      analyses will need to be conducted to determine whether these genotypes can be
      used as predictive markers for favorable therapeutic outcome. In this review, we
      discuss factors that affect response to mAb-based tumor therapies such as hu14.18
      IL2. Many of our observations have been made in the context of NBL; however, we
      will also include some observations made with mAbs targeting other tumor types
      that are consistent with results in NBL. Therefore, we hypothesize that the NBL
      observations discussed here may also be relevant to mAb therapy for other
      cancers, in which ADCC is known to play a role.

PMID- 22623919
TI  - Cortisol-induced increases of plasma oxytocin levels predict decreased immediate
      free recall of unpleasant words.
AB  - Cortisol and oxytocin have been shown to interact in both the regulation of
      stress responses and in memory function. In the present study we administered
      cortisol to 35 healthy female subjects in a within-subject double-blind placebo
      controlled design, while measuring oxytocin levels, adrenocorticotropic hormone
      (ACTH) levels, and free recall of pleasant and of unpleasant words. We found that
      cortisol administration suppressed ACTH levels and (1) induced a decrease in
      oxytocin associated with ACTH suppression and (2) an increase in oxytocin that
      was independent from ACTH suppression. This cortisol-induced increase in plasma
      oxytocin was associated with a selective decrease in immediate free recall of
      unpleasant words from primacy positions. The present results add to evidence that
      cortisol-induced increases in oxytocin could mediate some of the effects of
      stress and cortisol on memory, and possibly play a role in the regulation of the
      hypothalamo-pituitary-adrenal stress response. This mechanism could significantly
      impact affective and social behaviors, in particular during times of stress.

PMID- 22623920
TI  - Task-irrelevant auditory feedback facilitates motor performance in musicians.
AB  - An efficient and fast auditory-motor network is a basic resource for trained
      musicians due to the importance of motor anticipation of sound production in
      musical performance. When playing an instrument, motor performance always goes
      along with the production of sounds and the integration between both modalities
      plays an essential role in the course of musical training. The aim of the present
      study was to investigate the role of task-irrelevant auditory feedback during
      motor performance in musicians using a serial reaction time task (SRTT). Our
      hypothesis was that musicians, due to their extensive auditory-motor practice
      routine during musical training, have superior performance and learning
      capabilities when receiving auditory feedback during SRTT relative to musicians
      performing the SRTT without any auditory feedback. Behaviorally, we found that
      auditory feedback reinforced SRTT performance of the right hand (referring to
      absolute response speed) while learning capabilities remained unchanged. This
      finding highlights a potential important role for task-irrelevant auditory
      feedback in motor performance in musicians, a finding that might provide further
      insight into auditory-motor integration independent of the trained musical
      context.

PMID- 22623921
TI  - Recovery of vestibular ocular reflex function and balance control after a
      unilateral peripheral vestibular deficit.
AB  - This review describes the effect of unilateral peripheral vestibular deficit
      (UPVD) on balance control for stance and gait tests. Because a UPVD is normally
      defined based on vestibular ocular reflex (VOR) tests, we compared recovery
      observed in balance control with patterns of recovery in VOR function. Two
      general types of UPVD are considered; acute vestibular neuritis (AVN) and
      vestibular neurectomy. The latter was subdivided into vestibular loss after
      cerebellar pontine angle tumor surgery during which a vestibular neurectomy was
      performed, and vestibular loss following neurectomy to eliminate disabling
      Meniere's disease. To measure balance control, body-worn gyroscopes, mounted near
      the body's center of mass (CoM), were used. Measurement variables were the pitch
      (anterior-posterior) and roll (lateral) sway angles and angular velocities of the
      lower trunk/pelvis. Both patient groups showed balance deficits during stance
      tasks on foam, especially with eyes closed when stable balance control is
      normally highly dependent on vestibular inputs. Deficits during gait were also
      present and were more profound for complex gait tasks such as tandem gait than
      simple gait tasks. Major differences emerged between the groups concerning the
      severity of the deficit and its recovery. Generally, the effects of acute
      neuritis on balance control were more severe but recovered rapidly. Deficits due
      to vestibular neurectomy were less severe, but longer lasting. These results
      mostly paralleled recovery of deficits in VOR function. However, questions need
      to be raised about the effect on balance control of the two modes of neural
      plasticity occurring in the vestibular system following vestibular loss due to
      neuritis: one mode being the limited central compensation for the loss, and the
      second mode being some restoration of peripheral vestibular function. Future work
      will need to correlate deficits in balance control during stance and gait more
      exactly with VOR deficits and carefully consider the differences between
      insufficient central compensation compared to inadequate peripheral restoration
      of function.

PMID- 22623922
TI  - Fine-Tuning of Mast Cell Activation by FcepsilonRIbeta Chain.
AB  - Mast cells play a key role in allergic reaction and disorders through the high
      affinity receptor for IgE (Fc(epsilon)RI) which is primarily activated by IgE and
      antigen complex. In humans, mast cells express two types of Fc(epsilon)RI on the
      cell surface, tetrameric alphabetagamma(2) and trimeric alphagamma(2), whereas in
      mice, the tetrameric alphabetagamma(2) type is exclusively expressed. In human
      allergic inflammation lesions, mast cells increase in number and preferentially
      express the alphabetagamma(2) type Fc(epsilon)RI. By contrast, in the lesion of
      non-allergic inflammation, mast cells mainly express the alphagamma(2)type. Since
      the beta chain amplifies the expression and signaling of FcepsilonRI, mast cell
      effector functions and allergic reaction in vivo are enhanced in the presence of
      the beta chain. In contrast, a truncated beta chain-isoform (betaT) inhibits
      FcepsilonRI surface expression. The human Fc(epsilon)RIbeta gene contains seven
      exons and a repressor element located in the forth intron, through which
      Fc(epsilon)RIbeta transcription is repressed in the presence of GM-CSF. Regarding
      the additional signal regulatory function of the beta chain, the beta chain ITAM
      has dual (positive and negative) functions in the regulation of the mast cell
      activation. Namely, the Fc(epsilon)RIbeta chain ITAM enhances the mast cell
      activation signal triggered by a low-intensity (weak) stimulation whereas it
      suppresses the signal triggered by high-intensity (strong) stimulation. In an
      oxazolone-induced mouse CHS model, IgE-mediated mast cell activation is required
      and the beta chain ITAM is crucially involved. Adenosine receptor, one of the
      GPCRs, triggers a synergistic degranulation response with FcepsilonRI in mast
      cells, for which the beta chain ITAM critically plays positive role, possibly
      reflecting the in vivo allergic response. These regulatory functions of the
      FcepsilonRIbeta ITAM finely tune FcepsilonRI-induced mast cell activation
      depending on the stimulation strength, enabling the Fc(epsilon)RIbeta chain to
      become a potential molecular target for the development of new strategies for
      therapeutic interventions for allergies.

PMID- 22623924
TI  - MicroRNAs and Fetal Brain Development: Implications for Ethanol Teratology during
      the Second Trimester Period of Neurogenesis.
AB  - Maternal ethanol consumption during pregnancy can lead to a stereotypic cluster
      of fetal craniofacial, cardiovascular, skeletal, and neurological deficits that
      are collectively termed the fetal alcohol spectrum disorder (FASD). Fetal ethanol
      exposure is a leading non-genetic cause of mental retardation. Mechanisms
      underlying the etiology of ethanol teratology are varied and complex. This review
      will focus on the developing brain as an important and vulnerable ethanol target.
      Near the end of the first trimester, and during the second trimester, fetal
      neural stem cells (NSCs) produce most of the neurons of the adult brain, and
      ethanol has been shown to influence NSC renewal and maturation. We will discuss
      the neural developmental and teratological implications of the biogenesis and
      function of microRNAs (miRNAs), a class of small non-protein-coding RNAs that
      control the expression of gene networks by translation repression. A small but
      growing body of research has identified ethanol-sensitive miRNAs at different
      stages of NSC and brain maturation. While many miRNAs appear to be vulnerable to
      ethanol at specific developmental stages, a few, like the miR-9 family, appear to
      exhibit broad vulnerability to ethanol across multiple stages of NSC
      differentiation. An assessment of the regulation and function of these miRNAs
      provides important clues about the mechanisms that underlie fetal vulnerability
      to alterations in the maternal-fetal environment and yields insights into the
      genesis of FASD.

PMID- 22623925
TI  - Functional environmental genomics of a municipal landfill soil.
AB  - We investigated the toxicity of soil samples derived from a former municipal
      landfill site in the South of the Netherlands, where a bioremediation project is
      running aiming at reusing the site for recreation. Both an organic soil extract
      and the original soil sample was investigated using the ISO standardized Folsomia
      soil ecotoxicological testing and gene expression analysis. The 28 day
      survival/reproduction test revealed that the ecologically more relevant original
      soil sample was more toxic than the organic soil extract. Microarray analysis
      showed that the more toxic soil samples induced gene regulatory changes in twice
      as less genes compared to the soil extract. Consequently gene regulatory changes
      were highly dependent on sample type, and were to a lesser extent caused by
      exposure level. An important biological process shared among the two sample types
      was the detoxification pathway for xenobiotics (biotransformation I, II, and III)
      suggesting a link between compound type and observed adverse effects. Finally, we
      were able to retrieve a selected group of genes that show highly significant dose
      dependent gene expression and thus were tightly linked with adverse effects on
      reproduction. Expression of four cytochrome P450 genes showed highest correlation
      values with reproduction, and maybe promising genetic markers for soil quality.
      However, a more elaborate set of environmental soil samples is needed to validate
      the correlation between gene expression induction and adverse phenotypic effects.

PMID- 22623926
TI  - An emphasis on the wide usage and important role of local anesthesia in
      dentistry: A strategic review.
AB  - Local anesthesia forms the major part of pain-control techniques in dentistry.
      The prevention and elimination of pain during dental treatment has benefited
      patients, their doctors and dental hygienists, enabling the dental profession to
      make tremendous therapeutic advances that would otherwise have been impossible.
      Introduced in the late 1940s, the amide local anesthetics represent the most used
      drugs in dentistry. Local anesthetics also represent the safest and most
      effective drugs in all of medicine for the prevention and management of pain.
      They are also accompanied by various adverse effects which should be well known
      and be able to be controlled by the clinician. The article reviews the types of
      agents used as local anesthetics and their effects on the human body.

PMID- 22623927
TI  - Load-deflection and surface properties of coated and conventional superelastic
      orthodontic archwires in conventional and metal-insert ceramic brackets.
AB  - BACKGROUND: Properties of coated archwires, which have been introduced for
      esthetic demands during orthodontic treatments, along with the use of tooth
      colored brackets, are not clear. The aim of this study is to compare the load
      deflection and surface properties of coated superelastic archwires with
      conventional superelastic archwires in conventional and metal-insert ceramic
      brackets. MATERIALS AND METHODS: In this experimental study, 3 types of archwires
      including ultraesthetic polycoated, ultraesthetic epoxyresin coated and
      conventional (uncoated) superelastic nickel-titanium (NiTi) archwires were used
      in each of 2 types of brackets including conventional and metal-insert ceramic.
      To simulate oral environment, all specimens were incubated in artificial saliva
      using thermocycling model and then were tested in three-bracket bending test
      machine. Loading and unloading forces, plateau gap and end load deflection point
      (ELDP) were recorded. Archwires were investigated with a stereomicroscope before
      and after the experiment. Two-way ANOVA and Tukey tests were used at P<0.05.
      RESULTS: Epoxyresin archwires produced lower forces (19 to 310 gr) compared to
      polycoated (61 to 359 gr) and NiTi (61 to 415 gr) (P<0.0001). The maximum ELDP
      (0.43 mm) was observed in epoxyresin archwires (P<0.001). Coatings of some
      epoxyresin wires were torn and of polycoated wires peeled off. Conventional
      ceramic bracket produced higher loading forces with polycoated and NiTi archwires
      and lower unloading forces with all 3 types of archwires compared to metal-insert
      type (P<0.05). CONCLUSION: Epoxyresin-coated archwire had the lowest force and
      highest ELDP. Coatings were not durable in these experimental conditions.
      Conventional ceramic bracket produced higher frictional force compared to metal
      insert type.

PMID- 22623923
TI  - Oral inflammatory diseases and systemic inflammation: role of the macrophage.
AB  - Inflammation is a complex reaction to injurious agents and includes vascular
      responses, migration, and activation of leukocytes. Inflammation starts with an
      acute reaction, which evolves into a chronic phase if allowed to persist
      unresolved. Acute inflammation is a rapid process characterized by fluid
      exudation and emigration of leukocytes, primarily neutrophils, whereas chronic
      inflammation extends over a longer time and is associated with lymphocyte and
      macrophage infiltration, blood vessel proliferation, and fibrosis. Inflammation
      is terminated when the invader is eliminated, and the secreted mediators are
      removed; however, many factors modify the course and morphologic appearance as
      well as the termination pattern and duration of inflammation. Chronic
      inflammatory illnesses such as diabetes, arthritis, and heart disease are now
      seen as problems that might have an impact on the periodontium. Reciprocal
      effects of periodontal diseases are potential factors modifying severity in the
      progression of systemic inflammatory diseases. Macrophages are key cells for the
      inflammatory processes as regulators directing inflammation to chronic
      pathological changes or resolution with no damage or scar tissue formation. As
      such, macrophages are involved in a remarkably diverse array of homeostatic
      processes of vital importance to the host. In addition to their critical role in
      immunity, macrophages are also widely recognized as ubiquitous mediators of
      cellular turnover and maintenance of extracellular matrix homeostasis. In this
      review, our objective is to identify macrophage-mediated events central to the
      inflammatory basis of chronic diseases, with an emphasis on how control of
      macrophage function can be used to prevent or treat harmful outcomes linked to
      uncontrolled inflammation.

PMID- 22623928
TI  - Recharge pattern of contemporary glass ionomer restoratives.
AB  - BACKGROUND: As glass ionomers have the ability to reload fluoride from outside
      sources, the aim was to compare the recharge pattern of six glass ionomer cements
      after exposure to fluoride. MATERIALS AND METHODS: Fuji VII, Fuji IX, Riva Pink,
      Riva Bleach, Ketac Fil and Fuji IX Extra were investigated. The fluoride
      containing materials used were tooth paste and mouth wash (Colgate). Specimens of
      each material (n=15) were immersed separately in deionized water for 59 days.
      Then the samples of each material were divided into three groups of five each.
      Two groups were recharged for 2, 20 and 60 min daily during three consecutive
      weekly intervals and then no treatment for one week. The third group was used as
      control. Fluoride release measurements (MUg/cm(2)/day) were made in every 24 h.
      One-way and repeated measures analysis of variance tests were used. RESULTS:
      Tooth paste recharged materials showed higher level of recharge. On day 1, the
      difference of fluoride release from different treatment groups of different
      materials except for Fuji IX Extra were not significant (P>0.05). On days 7 and
      14, the differences observed were significant (P<0.05) for all materials except
      for Fuji VII (tooth paste versus mouth wash) and Trial Fuji IX (mouth wash versus
      control) and on day 14 for Rvia Pink (mouth wash versus control). On days 21 and
      28, the differences observed were significant for all the materials (P<0.05)
      except for Riva Pink (toothpaste versus mouth wash), Riva Bleach, Ketac Fil and
      Trial FujiI X (mouth wash versus control) on day 28. CONCLUSION: A time tabled
      schedule of application of fluoride-containing materials could help to achieve
      high fluoride release.

PMID- 22623929
TI  - Comparison of the cleaning capacity of Mtwo and Pro Taper rotary systems and
      manual instruments in primary teeth.
AB  - BACKGROUND: Root canal cleaning is an important step in endodontic therapy. In
      order to develop better techniques, a new generation of endodontic instruments
      has been designed. The aim of this study was to compare the effectiveness of
      manual K-files (Mani Co, Tokyo, Japan) and two rotary systems-Mtwo (Dentsply
      Maillefer, Ballaigues, Switzerland) and ProTaper (VDW, Munich, Germany)-for root
      canal preparation in primary molars. MATERIALS AND METHODS: India ink was
      injected to 160 mesiobuccal and distal root canals of mandibular primary molars.
      The teeth were randomly divided into three experimental groups and one control
      group. In each experimental group, either manual instruments (K-files) or rotary
      instruments (Mtwo or ProTaper) were used to prepare root canals. After cleaning
      the canals and clearing the teeth, ink removal was evaluated with a
      stereomicroscope. Statistical analysis was done with Kruskal-Wallis and Friedman
      tests. RESULTS: There were no significant differences in cleaning efficiency
      between manual and rotary instruments. Only ProTaper files performed
      significantly better in the coronal and middle thirds than in the apical third of
      the root canal. CONCLUSION: Manual K-files and the Mtwo and ProTaper rotary
      systems showed equally acceptable cleaning ability in primary molar root canals.

PMID- 22623930
TI  - Prevalence of eruption status of third molars in Libyan students.
AB  - BACKGROUND: The aim of the present study is to determine the number of third
      molars per person, angulation, level, amount of space for eruption of third molar
      between ramus of mandible and second molar and the eruption status of third molar
      in a group of Libyan students, with different impaction patterns and agenesis of
      third molars. MATERIALS AND METHODS: In this descriptive retrospective study, a
      total of 200 students (100 male and 100 female students of bachelor of dental
      surgery, Faculty of Dentistry, Garyounis University, Benghazi, Libya) were
      enrolled. Students who had complete complement of teeth within the age group 17
      26 years were selected for this study, while those cases who had history of
      extraction of any of the teeth or who refused to give consent were excluded.
      Before starting the study, ethical concern from the ethical committee, IRB and
      informed consent from each student who underwent radiography were obtained.
      RESULTS: The results showed that 5% of third molars were congenitally missing.
      Approximately 93.5% of the subjects had all four third molars, 1% had two third
      molars and 0.5% had one third molars with 2.5% having agenesis of all third
      molars. Third molar agenesis showed predilection for maxilla with higher
      proportion in females (3%) than males (2.1%). Angular position was maximum with
      vertical position (5.83%), with least being horizontal impactions. Level of
      occlusal plane of third molar similar to that of adjacent tooth was seen in
      44.74%, below the occlusal plane in 24.76%, totally impacted noted in 30%.
      CONCLUSION: The present study showed that 33% of the teeth were fully erupted and
      66% were in various stages of eruption and 5% were congenitally missing in these
      students.

PMID- 22623931
TI  - Plasma zinc antioxidant vitamins, glutathione levels and total antioxidant
      activity in oral leukoplakia.
AB  - BACKGROUND: Leukoplakia is a common, potentially premalignant lesion with
      malignant transformation rate from 1 to 17% with highest transformation rate for
      the lesions on the floor of the mouth, soft palate and tongue. One of the main
      etiological factors is consuming areca nut and its commercial preparations which
      generate high levels of reactive oxygen species during their metabolism. So the
      aim of this present study is to evaluate the plasma levels of antioxidant
      vitamins, antioxidant mineral zinc, glutathione and total antioxidant status
      (TAS) in leukoplakia patients. MATERIALS AND METHODS: For this cross-sectional
      study, we selected 23 newly diagnosed oral leukoplakia patients of both sexes
      within the age group 28-40 years and the same number of age and sex matched
      healthy individuals without having history of any systemic illness were selected
      as control group. In both the groups, we measured plasma antioxidant vitamins A,
      C, E, antioxidant mineral zinc, GSH and TAS. Student's t test was applied and the
      P value <0.001 was considered as statistically significant. RESULTS: We observed
      very low levels of antioxidant vitamins A, C, E, antioxidant mineral zinc and
      antioxidant metabolite GSH (P<0.001) and at the same time we also observed very
      poor (TAS) (P<0.001) in leukoplakia patients when compared to patients in control
      group. CONCLUSION: The consumption of tobacco or areca quid which contains high
      copper levels creates an oxidative stress like environment during their
      metabolism, might play a major role in causation and propagation of oral
      leukoplakia.

PMID- 22623932
TI  - HSP27 and HSP70 expression in squamous cell carcinoma: An immunohistochemical
      study.
AB  - BACKGROUND: Heat shock proteins (HSPs) are a family of proteins that are known to
      play a significant role in the repair of denatured proteins in the cell. It seems
      that cytoprotective properties of HSPs may help in malignant progression by
      facilitating tumor cell growth and survival. The purpose of this study is to
      evaluate HSP27 and HSP70 expression in various histopathological grades of
      squamous cell carcinoma (SCC). MATERIALS AND METHODS: In this retrospective
      analytical study, the sections of 51 formalin-fixed paraffin-embedded biopsy
      specimens of SCC from various sites of oral and paraoral regions and 10 normal
      oral mucosa were immunostained by Novolink Polymer technique to determine the
      expression of HSP27 and HSP70. Then the data were analyzed according to the
      Kruskal-Walis, Mann-Whitney and the Spearman correlation tests (P<0.05). RESULTS:
      The expression of HSP27 in well-differentiated SCC was significantly higher than
      normal epithelium (P=0.007) and in moderately differentiated SCC higher than
      poorly-differentiated SCC (P=0.023). Inverse correlation was observed between
      HSP27 expression and SCC's histopathological grade (P=0.001, r=-0.448). There was
      no significant difference between HSP70 staining of specimens (P=0.38).
      CONCLUSIONS: The present study revealed that the expression level of HSP27 was
      inversely related to histopathological grade of SCC and it may provide prognostic
      value for patients with SCC, but there was no significant relationship between
      the expression of HSP70 and histopathological grades of SCC.

PMID- 22623933
TI  - Evaluation of the antibacterial effect of calcium hydroxide in combination with
      three different vehicles: An in vitro study.
AB  - INTRODUCTION: Antimicrobial activity of interappointment intracanal medications
      is an important consideration in endodontics. Considering the fact that calcium
      hydroxide (CH) cannot sterilize the root canal system, completing its
      antimicrobial spectrum seems necessary. The aim of this study was to compare the
      antibacterial activity of CH combined with three different vehicles in root canal
      system. MATERIALS AND METHODS: In this in vitro experimental study, 61 freshly
      extracted human single rooted teeth were used. After chemo-mechanical
      preparation, the teeth were dressed with CH in combination with: G1: Distilled
      water (DW); G2: 5.25% sodium hypochlorite; G3: 0.2% chlorhexidine solution. All
      teeth were mounted in a 2-chamber apparatus. After sterilization, the coronal
      chamber was exposed to bacteria and the apical chamber was filled with broth for
      90 days. Leakage was recorded when turbidity was observed in broth. Mean times of
      leakage and turbidity percentage were recorded for each group. Data were analyzed
      by One Way ANOVA test (alpha=0.005). RESULTS: The highest mean time of
      contamination was for chorhexidine/CH combination (M=66.76 days), and the lowest
      was for DW/CH combination (M=40.29 days). Statistically significant difference
      was observed between G3 and G1 (P=0.042), but the difference between G2 and G3
      (P=0.76) or G1 and G2 (P=0.18) were not significant. 88.23% of the samples of G1,
      70.58% of G2, and 64.70% of G3 were contaminated after 3 months. CONCLUSION: As
      an intracanal medication, the chlorhexidine/CH combination had significantly more
      antibacterial activity than DW/CH combination.

PMID- 22623934
TI  - Novel bioactive Co-based alloy/FA nanocomposite for dental applications.
AB  - BACKGROUND: Dental cobalt base alloys are biocompatible dental materials and have
      been widely used in dentistry. However, metals are bioinert and may not present
      bioactivity in human body. Bioactivity is the especial ability to interact with
      human body and make a bonding to soft and hard tissues. The aim of the present
      research was fabrication and bioactivity evaluation of novel cobalt
      alloy/Fluorapatite nanocomposite (CoA/FaNC) with different amounts of
      Fluorapatite (FA) nanopowder. MATERIALS AND METHODS: Co-Cr-Mo alloy (ASTM F75)
      powder was prepared and mixed in a planetary ball mill with different amounts of
      FA nanopowders (10, 15, 20% wt). Prepared composite powders were cold pressed and
      sintered at 1100 degrees C for 4 h. X-ray diffraction (XRD), scanning electron
      microscopy and transition electron microscopy techniques were used for phase
      analysis, crystallite size determination of FA and also for phase analysis and
      evaluation of particle distribution of composites. Bioactivity behavior of
      prepared nanocomposites was evaluated in simulated body fluid (SBF) for 1 up to
      28 days. MATERIALS AND METHODS: Co-Cr-Mo alloy (ASTM F75) powder was prepared and
      mixed in a planetary ball mill with different amounts of FA nanopowders (10, 15,
      20% wt). Prepared composite powders were cold pressed and sintered at 1100
      degrees C for 4 h. X-ray diffraction (XRD), scanning electron microscopy and
      transition electron microscopy techniques were used for phase analysis,
      crystallite size determination of FA and also for phase analysis and evaluation
      of particle distribution of composites. Bioactivity behavior of prepared
      nanocomposites was evaluated in simulated body fluid (SBF) for 1 up to 28 days.
      RESULTS: Results showed that nucleus of apatite were formed on the surface of the
      prepared CoA/FaNC during 1 up to 28 days immersion in the SBF solution. On the
      other hand, CoA/FaNC unlike Co-base alloy possessed bone-like apatite-formation
      ability. CONCLUSION: It was concluded that bioinert Co-Cr-Mo alloy could be
      successfully converted into bioactive nanocomposite by adding 10, 15, 20 wt% of
      FA nano particles.

PMID- 22623935
TI  - Mast cells distribution and variations in epithelium thickness and basement
      membrane in oral lichen planus lesion and oral lichenoid reaction.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic mucocutaneous lesion with
      unknown etiology. Oral lichenoid lesions (OLL) comprise a family of lesions with
      different etiologies. Both lesions have similar clinical and histopathologic
      characteristics although their management is different. Differential diagnosis
      between OLP and OLL has always been a major challenge. MATERIALS AND METHODS: In
      this prospective analytical study, the role of mast cells in pathogenesis of
      these lesions was investigated by evaluation of 52 patients with clinical and
      histopathological diagnosis of OLP (26 cases) and OLL (26 cases) based on WHO
      criteria, and by applying a more accessible staining methods, Hematoxylin and
      Eosin, toluidine blue (histochemistry) and Periodic Acid Schiff staining. In
      order to distinguish these two lesions, number of mast cells and thickness of
      epithelium and basement membrane were measured using light microscopy. Data were
      analyzed by SPSS software using t-test method (P<0.001). RESULTS: No significant
      difference was observed between the total numbers of mast cells of two groups
      (P=0.148), but a statistically significant difference was detected between
      degranulated mast cells in two groups (P<0.001). A significant difference was
      also observed between the thickness of epithelium in two groups (P<0.001),
      although no difference was seen between basement membrane thickness in these
      lesions. CONCLUSION: Number of degranulated mast cells in reticular layer of
      corium in lichenoid lesions was more than that of OLP. This implies that despite
      the increase in number of these cells, in both groups of diseases, the role of
      these cells has not been the same in pathogenesis of the diseases. Moreover, the
      epithelium thickness was lower in lesions of OLP compared to lesions of oral
      lichenoid, so this parameter may be a useful criterion together with other
      histopathological and clinical finding to discriminate these lesions. However,
      discrepancy of basement membrane thickness can not be a reliable criterion.
      Finally we suggest more accessible staining methods which are reliable for
      differentiation of these two lesions.

PMID- 22623936
TI  - Fracture resistance of structurally compromised and normal endodontically treated
      teeth restored with different post systems: An in vitro study.
AB  - BACKGROUND: With the aim of developing methods that could increase the fracture
      resistance of structurally compromised endodontically treated teeth, this study
      was conducted to compare the effect of three esthetic post systems on the
      fracture resistance and failure modes of structurally compromised and normal
      roots. MATERIALS AND METHODS: Forty five extracted and endodontically treated
      maxillary central teeth were assigned to 5 experimental groups (n=9). In two
      groups, the post spaces were prepared with the corresponding drills of the post
      systems to be restored with double taper light posts (DT.Light-Post) (group DT.N)
      and zirconia posts (Cosmopost) (group Zr.N). In other 3 groups thin wall canals
      were simulated to be restored with Double taper Light posts (DT.W), double taper
      Light posts and Ribbond fibers (DT+R.W) and Zirconia posts (Zr.W). After access
      cavity restoration and thermocycling, compressive load was applied and the
      fracture strength values and failure modes were evaluated. Data were analyzed
      using two-way ANOVA, Tukey and Fisher exact tests (P<0.05). RESULTS: The mean
      failure loads (N) were 678.56, 638.22, 732.44, 603.44 and 573.67 for groups DT.N,
      Zr.N, DT.W, DT+R.W and Zr.w respectively. Group DT+R.W exhibited significantly
      higher resistance to fracture compared to groups Zr.N, DT.W and Zr.w (P<0.05). A
      significant difference was detected between groups DT.N and Zr.W (P=0.027).
      Zirconia posts showed significantly higher root fracture compared to fiber posts
      (P=0.004). CONCLUSION: The structurally compromised teeth restored with double
      taper light posts and Ribbond fibers showed the most fracture resistance and
      their strengths were comparable to those of normal roots restored with double
      taper light posts. More desirable fracture patterns were observed in teeth
      restored with fiber posts.

PMID- 22623937
TI  - A comparative immunohistochemical study of Ki-67 and Bcl-2 expression in solid
      ameloblastoma and adenomatoid odontogenic tumor.
AB  - BACKGROUND: Solid ameloblastoma (SAB) is an invasive tumor which infiltrates
      adjacent normal tissues. Adenomatoid odontogenic tumor is a noninvasive tumor and
      never infiltrates surrounding normal tissues. The purpose of this study was to
      determine the biological behavior of these two epithelial odontogenic neoplasm by
      detecting Ki-67 and Bcl-2, which are mitotic and anti apoptotic markers
      respectively. MATERIALS AND METHODS: In this analytical retrospective study, 16
      samples of SAB and 16 samples of adenomatoid odontogenic tumor were selected. The
      samples were deparafinized and antigens were retrieved. Immunohistochemistry
      technique was applied for evaluation of these two markers. Monoclonal antibodies
      MIB1 and Bcl-2 were used to detect Ki-67 and Bcl-2 protein respectively, then the
      labeling index (LI) was calculated for both markers according to cellular
      staining. Data were analyzed by "t" test, (P<0.05). RESULTS: The mean values of
      LI for Ki-67 in SAB and Adenomatiod odontogenic tumor (AOT) were 4 and 1%
      respectively and for Bcl-2 in SAB and AOT were 63 and 26% respectively. The
      indices of both markers were higher in SAB compared to AOT (P <0.05).
      CONCLUSIONS: Higher percentage of these two markers in SAB compared to AOT
      confirms the aggressive behavior of SAB and the hamartomatosis behavior of AOT.

PMID- 22623938
TI  - Clinical evaluation of the essential oil of "Satureja Hortensis" for the
      treatment of denture stomatitis.
AB  - BACKGROUND: The prevalence of denture stomatitis has been shown to vary from 15
      to 65% in complete denture wearers. Satureja hortensis L. has been considered to
      have antinociceptive, anti-inflammatory, antifungal and antimicrobial activities
      in vitro and exhibits strong inhibitory effect on the growth of periodontal
      bacteria. The aim of this study was to evaluate the efficacy of a 1% gel
      formulation of S. hortensis essential oil for the treatment of denture
      stomatitis. MATERIALS AND METHODS: A randomized, controlled clinical trial study
      was conducted on 80 patients (mean age 62.91+/-7.34) in two parallel groups
      treated either with S. hortensis essential oil 1% gel or placebo applied two
      times daily for two weeks. Denture stomatitis was diagnosed by clinical
      examination and paraclinical confirmation with sampling the palatal mucosa for
      Candida albicans. Data were analyzed using Chi-squared or Student's t tests.
      RESULTS: The erythematous lesions of palatal area were significantly reduced
      (P<0.0001) in the treatment group who applied 1% topical gel of S. hortensis
      essential oil and Candida colonies count were reduced significantly (P=0.001).
      CONCLUSION: Topical application of the essential oil of S. hortensis could be
      considered as an effective agent for the treatment of denture stomatitis.

PMID- 22623939
TI  - Determination of orthodontic tooth movement and tissue reaction following
      demineralized freeze-dried bone allograft grafting intervention.
AB  - BACKGROUND: Socket preservation after tooth extraction is one of the indications
      of bone grafting to enhance preorthodontic condition. The aim of this study is to
      determine the effects of socket preservation on the immediate tooth movement,
      alveolar ridge height preservation and orthodontic root resorption. MATERIALS AND
      METHODS: In a split-mouth technique, twelve sites in three dogs were investigated
      as an experimental study. Crushed demineralized freeze-dried bone allograft
      (DFDBA) (CenoBone((r))) was used as the graft material. The defects were made by
      the extraction of 3(rd) premolar. On one side of each jaw, the defects were
      preserved by DFDBA and defects of the other side left opened as the control
      group. Simultaneously the teeth adjacent to the defects were pulled together by a
      NiTi coil spring. After eight weeks, the amount of (OTM), alveolar height, and
      root resorption were measured. Analysis of variance was used for purpose of
      comparison. RESULTS: There was a slight increase in OTM at grafted sites as they
      were compared to the control sites (P<0.05). Also a significant bone resorption
      in control site and successful socket preservation in experimental site were
      observed. Reduction of root resorption at the augmented site was significant
      compared to the normal healing site (P<0.05). CONCLUSION: Using socket
      preservation, tooth movement can be immediately started without waiting for the
      healing of the recipient site. This can provide some advantages like enhanced
      rate of OTM, its approved effects on ridge preservation that reduces the chance
      of dehiscence and the reduction of root resorption.

PMID- 22623940
TI  - Oral health of psychiatric patients: A cross-sectional comparision study.
AB  - BACKGROUND: Mental illness is associated with physical health. Oral health
      affects people physically and psychologically and influences how they grow, enjoy
      life, look, speak, chew, taste food and socialize. Oral health may have lower
      priority in the context of mental illness and these diverse and changing client
      group experiences similar oral and dental problems. OBJECTIVE: To assess oral
      health problems in psychiatric patients. MATERIALS AND METHODS: This cross
      sectional study included 133 patients attending the psychiatric outpatient
      department (OPD) as the study group and 133 patients attending the general OPD of
      the same hospital as the control group. Both groups were examined for oral health
      status. RESULTS: Mean age of the study group was 40.2 years, 66.17% were males,
      66.17% were married and 83.67% belonged to middle or lower class. 39.8% of
      patients had mental illness for 1-5 years, 88% were self sufficient and 34.6% had
      healthy oral practices. These results are very much comparable with the control
      group. Mean decayed missed filled teeth (DMFT) score (2.10) and mean oral hygiene
      index-simplex (OHI-S) score (3.6) increased with age. Difference in DMFT score
      with age was not statistically significant (P>0.5) while it was highly
      significant for OHI-S score (P<0.0001). Periodontal condition worsened as age
      increased, suggested by community periodontal index. Only 26.7% of patients had
      healthy gingiva in the age group 20-50 years while it was zero for 50 years and
      above. This difference is statistically significant (P<0.001).

PMID- 22623941
TI  - Microflora around teeth and dental implants.
AB  - BACKGROUND: When an implant is exposed to oral cavity, its surface gets colonized
      by micro-organisms. The aim of this study is to comparatively assess the
      microbiological parameters in sulci around the teeth and the crowns supported by
      dental implants. MATERIALS AND METHODS: In this prospective, cross-sectional
      study, 34 partially edentulous patients aged between 40 and 50 years with total
      50 anterior maxillary single implants with cemented crowns (depth of sulci <4 mm)
      and 34 similar teeth in the same jaw of the same patients were included. Excluded
      were the patients with compromised systemic and periodontal health and smoking
      habits. None of the patients had used any antimicrobial mouthwashes during at
      least two weeks before the study. All of the implants (ITI) were at least 6
      months in place covered by definitive prostheses. Samples of gingival sulci were
      taken around teeth with paper cone and transported to Stuart transport medium.
      Samples were cultured and examined by a dark field microscope and eight
      laboratory tests were performed to determine the micro-organisms The data were
      evaluated statistically using Chi-square test (alpha=0.05). RESULTS: Six anerobic
      bacteria found in teeth and implants sulci were Gram-positive cocci, Gram
      negative cocci, Prevotella, Porphyromonas gingivalis, Bacteroid Fragilis and
      Fusobacterium. Gram-positive cocci and Gram-negative cocci had maximum and
      minimum percentage frequency in the two groups, respectively. There were no
      significant differences between the two groups (P value >0.05). CONCLUSION: The
      present study indicated that microflora in implant sulci is similar to the tooth
      sulci, when the depth of sulci is normal (<4 mm). As a result, implants'
      susceptibility to inflammation is the same as teeth.

PMID- 22623942
TI  - The study of relationship between reported temporomandibular symptoms and
      clinical dysfunction index among university students in Shiraz.
AB  - BACKGROUND: This study was designed to evaluate the correlation between
      subjective data obtained from a questionnaire and clinical examination among
      students in Shiraz university of medical sciences. MATERIALS AND METHODS: In this
      cross-sectional prospective study, the samples consisted of 200 subjects, with
      equal distribution between males and females. Subjects' ages ranged from 18 to 30
      years (24.07+/-2.93). A functional evaluation was performed using the Helkimo
      clinical dysfunction (Di) and anamnestic (Ai) indices. Data were evaluated by the
      Chi-square test between gender and clinical dysfunction index (Di) and
      correlation coefficient between Di and Ai (the level of significance was set at
      P<0.05). RESULTS: Among the total study population, 30% reported mild symptoms
      (Ai I) while 2% had severe (Ai II). In the clinical examination, 71% showed some
      degree of dysfunction. These degrees were as follows: 50% were classified as mild
      (Di I), 13% moderate (Di II) and 8% severe signs and symptoms (Di III). With
      respect to gender, women (80%) were more affected than men (62%). A significant
      relationship was found between gender and the occurrence of temporomandibular
      disorder (TMD) (P<0.05). The correlation coefficient (r) between the reported
      symptoms (Ai) and recorded signs (Di) was 0.53. There were positive correlation
      coefficient between Di and Ai. They were statistically significant (P<0.001).
      CONCLUSIONS: A high prevalence of signs and symptoms of TMD among students in
      Shiraz University of Medical Sciences was seen, which was greater in women.
      Despite suffering from TMD, students were not aware of their disorders.

PMID- 22623943
TI  - Five years follow-up of implant-prosthetic rehabilitation on a patient after
      mandibular ameloblastoma removal and ridge reconstruction by fibula graft and
      bone distraction.
AB  - This case report presents a combination of surgical and prosthetic solutions
      applied to a case of oral implant rehabilitation in post-oncologic reconstructed
      mandible. Bone resection due to surgical treatment of large mandibular neoplasm
      can cause long-span defects. Currently, mandibular fibula free flap graft is
      widely considered as a reliable technique for restoring this kind of defect. It
      restores the continuity of removed segment and re-establishes the contour of the
      lower jaw. However, the limited height of grafted fibula does not allow the
      insertion of regular length implants, therefore favouring vertical distraction
      osteogenesis as an important treatment choice. This report presents a patient
      affected by extensive mandibular ameloblastoma who underwent surgical
      reconstruction by fibula free flap because of partial mandibular resection.
      Guided distraction osteoneogenesis technique was applied to grafted bone, in
      order to obtain adequate bone height and to realize a prosthetically guided
      placement of 8 fixtures. After osseointegration, the patient was rehabilitated
      with a full arch, screw-retained prosthetic restoration. At five-years follow up,
      excellent integration of grafted tissue, steady levels of bone around the
      fixtures and healthy peri-implant tissues were reported.

PMID- 22623944
TI  - Recurrent CEOT of the maxilla.
AB  - Calcifying epithelial odontogenic tumor (CEOT) is a rare benign, but locally
      infiltrating odontogenic neoplasm. It accounts for less than 1% of all
      odontogenic tumors. This is a case report of recurrent CEOT in the maxilla. A 35
      year-old patient reported after three years of surgical excision of the lesion,
      with a recurrence. It is of particular concern because of its anatomic location
      in the maxilla. Maxillary tumors tend to be more aggressive and rapidly spreading
      and may involve the surrounding vital structures. Adequate resection of the
      lesion with disease-free surgical margins and long-term follow-up is recommended.

PMID- 22623945
TI  - Cardamom comfort.

PMID- 22623946
TI  - Innate Ideas Revisited: For a Principle of Persistence in Infants' Physical
      Reasoning.
AB  - The notion of innate ideas has long been the subject of intense debate in the
      fields of philosophy and cognitive science. Over the past few decades,
      methodological advances have made it possible for developmental researchers to
      begin to examine what innate ideas-what innate concepts and principles-might
      contribute to infants ' knowledge acquisition in various core domains. This
      article focuses on the domain of physical reasoning and on Spelke's (1988, 1994)
      proposal that principles of continuity and cohesion guide infants' interpretation
      of physical events. The article reviews recent evidence that these two principles
      are in fact corollaries of a single and more powerful principle of persistence,
      which states that objects persist, as they are, in time and space. 

PMID- 22623947
TI  - Health-related characteristics and dietary intakes of male veterans and non
      veterans in the Multiethnic Cohort Study (United States).
AB  - BACKGROUND: Nationwide surveys in the United States found that certain health
      related factors, in particular cigarette smoking and obesity, were more prevalent
      in veterans than in non-veterans.  PURPOSE: The objective of this paper was to
      compare health-related characteristics and dietary intakes between veterans and
      non-veterans in the Multiethnic Cohort.  MATERIALS AND METHODS: The cohort
      participants (aged 45-75 years), residing in Hawaii and California at baseline,
      completed a mailed questionnaire on diet, medical history, and lifestyle in 1993
      1996. The current analyses included 20,939 men (14,975 veterans and 5,964 non
      veterans) who returned a survey questionnaire on military service in 2007. 
      RESULTS: Compared to non-veterans, veterans were more likely to be overweight and
      obese (BMI>=25, 61% vs. 55%), former smokers (54% vs. 47%), heavier consumers of
      red and processed meat, and lighter consumers of fruits and vegetables. Within
      the veteran group, enlisted men were more likely to be obese, to have a history
      of smoking, to consume more processed meat and to consume smaller amounts of
      dairy products and fruits than officers.  CONCLUSION: The findings imply that
      veterans as a group are at somewhat higher risk of developing lifestyle-related
      chronic diseases than are non-veterans. Comparisons of actual differences in
      disease incidence and mortality in the Multiethnic Cohort between veterans and
      non-veterans will require several more years of follow-up.

PMID- 22623948
TI  - Patterns of attendance of children under 12 years at school dental service in
      Western australia.
AB  - The aim of this study was to investigate the patterns of attendance at School
      Dental Service (SDS) and reasons for attendance (treatment or prevention) for
      children in the Perth Metropolitan Area, in particular investigating the first
      year of SDS attendance and attendance until the year the child turned 12. The
      first 150 SDS records located for children from the Western Australian Pregnancy
      Cohort (Raine) Study were used for this study. Patterns of attendance of children
      at SDS were described, as were associated factors (enrolment, age and nature of
      first visit, general nature of visits and number of visits) until the end of the
      year that the child turned 12.The age of the child at the first SDS visit ranged
      from 4 years 3 months to 14 years 11 months, with a median of 5 years 1 month.
      First visits were primarily for an examination (98%). Children had a median of 13
      visits until 12 years of age, with 10% having less than five visits and 4% having
      more than 25 visits.These data provide useful information regarding attendance at
      the SDS in Western Australia which could provide a basis for oral health
      promotion programs.

PMID- 22623949
TI  - Five Consecutive Cases of Liquefied Aftercataract: Impact of Nd:YAG Laser
      Capsulotomy on Refraction and High-Order Aberrations.
AB  - For five consecutive eyes from five patients with liquefied aftercataract, Nd:YAG
      laser treatment significantly reduced high-order aberrations. Two eyes showing a
      reduction in positive spherical-like aberrations after treatment showed a
      postoperative myopic shift, while three eyes showing no change in spherical-like
      aberrations demonstrated hyperopic or only a slight myopic shift.

PMID- 22623950
TI  - Effects of varying temporal scale on spatial models of mortality patterns
      attributed to pediatric diarrhea.
AB  - Public health data is often highly aggregated in time and space. The consequences
      of temporal aggregation for modeling in support of policy decisions have largely
      been overlooked. We examine the effects of changing temporal scale on spatial
      regression models of pediatric diarrhea mortality patterns, mortality rates and
      mortality peak timing, in Mexico. We compare annual and decadal level univariate
      models that incorporate known risk factors. Based on normalized sums of squared
      differences we compare between annual and decadal coefficients for variables that
      were significant in decadal models. We observed that spurious relationships might
      be created through aggregating time scales; obscuring interannual variation and
      resulting in inflated model diagnostics. In fact, variable selection and
      coefficient values can vary with changing temporal aggregation. Some variables
      that were significant at the decadal level were not significant at the annual
      level. Implications of such aggregation should be part of risk communication to
      policy makers.

PMID- 22623951
TI  - Thymosin beta10 expression driven by the human TERT promoter induces ovarian
      cancer-specific apoptosis through ROS production.
AB  - Thymosin beta(10) (Tbeta(10)) regulates actin dynamics as a cytoplasm G-actin
      sequestering protein. Previously, we have shown that Tbeta(10) diminishes tumor
      growth, angiogenesis, and proliferation by disrupting actin and by inhibiting
      Ras. However, little is known about its mechanism of action and biological
      function. In the present study, we establish a new gene therapy model using a
      genetically modified adenovirus, referred to as Ad.TERT.Tbeta(10), that can
      overexpress the Tbeta(10) gene in cancer cells. This was accomplished by
      replacing the native Tbeta(10) gene promoter with the human TERT promoter in
      Ad.TERT.Tbeta(10). We investigated the cancer suppression activity of Tbeta(10)
      and found that Ad.TERT.Tbeta(10) strikingly induced cancer-specific expression of
      Tbeta(10) as well as apoptosis in a co-culture model of human primary ovarian
      cancer cells and normal fibroblasts. Additionally, Ad.TERT.Tbeta(10) decreased
      mitochondrial membrane potential and increased reactive oxygen species (ROS)
      production. These effects were amplified by co-treatment with anticancer drugs,
      such as paclitaxel and cisplatin. These findings indicate that the rise in ROS
      production due to actin disruption by Tbeta(10) overexpression increases
      apoptosis of human ovarian cancer cells. Indeed, the cancer-specific
      overexpression of Tbeta(10) by Ad.TERT.Tbeta(10) could be a valuable anti-cancer
      therapeutic for the treatment of ovarian cancer without toxicity to normal cells.

PMID- 22623952
TI  - Identification of a 4-microRNA signature for clear cell renal cell carcinoma
      metastasis and prognosis.
AB  - Renal cell carcinoma (RCC) metastasis portends a poor prognosis and cannot be
      reliably predicted. Early determination of the metastatic potential of RCC may
      help guide proper treatment. We analyzed microRNA (miRNA) expression in clear
      cell RCC (ccRCC) for the purpose of developing a miRNA expression signature to
      determine the risk of metastasis and prognosis. We used the microarray technology
      to profile miRNA expression of 78 benign kidney and ccRCC samples. Using 28
      localized and metastatic ccRCC specimens as the training cohort and the
      univariate logistic regression and risk score methods, we developed a miRNA
      signature model in which the expression levels of miR-10b, miR-139-5p, miR-130b
      and miR-199b-5p were used to determine the status of ccRCC metastasis. We
      validated the signature in an independent 40-sample testing cohort of different
      stages of primary ccRCCs using the microarray data. Within the testing cohort
      patients who had at least 5 years follow-up if no metastasis developed, the
      signature showed a high sensitivity and specificity. The risk status was proven
      to be associated with the cancer-specific survival. Using the most stably
      expressed miRNA among benign and tumorous kidney tissue as the internal reference
      for normalization, we successfully converted his signature to be a quantitative
      PCR (qPCR)-based assay, which showed the same high sensitivity and specificity.
      The 4-miRNA is associated with ccRCC metastasis and prognosis. The signature is
      ready for and will benefit from further large clinical cohort validation and has
      the potential for clinical application.

PMID- 22623953
TI  - Global microRNA expression profiling of high-risk ER+ breast cancers from
      patients receiving adjuvant tamoxifen mono-therapy: a DBCG study.
AB  - PURPOSE: Despite the benefits of estrogen receptor (ER)-targeted endocrine
      therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs)
      have been suggested as promising biomarkers and we here evaluated whether a miRNA
      profile could be identified, sub-grouping ER+ breast cancer patients treated with
      adjuvant Tamoxifen with regards to probability of recurrence. EXPERIMENTAL
      DESIGN: Global miRNA analysis was performed on 152 ER+ primary tumors from high
      risk breast cancer patients with an initial discovery set of 52 patients,
      followed by two independent test sets (N = 60 and N = 40). All patients had
      received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6
      years) and half had developed distant recurrence (median time-to-recurrence: 3.5
      years). MiRNA expression was examined by unsupervised hierarchical clustering and
      supervised analysis, including clinical parameters as co-variables. RESULTS: The
      discovery set identified 10 highly significant miRNAs that discriminated between
      the patient samples according to outcome. However, the subsequent two independent
      test sets did not confirm the predictive potential of these miRNAs. A significant
      correlation was identified between miR-7 and the tumor grade. Investigation of
      the microRNAs with the most variable expression between patients in different
      runs yielded a list of 31 microRNAs, eight of which are associated with stem cell
      characteristics. CONCLUSIONS: Based on the large sample size, our data strongly
      suggests that there is no single miRNA profile predictive of outcome following
      adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We
      identified a sub-group of Tamoxifen-treated breast cancer patients with miRNA
      expressing tumors associated with cancer stem cell characteristics.

PMID- 22623954
TI  - Avian influenza H9N2 seroprevalence among poultry workers in Pune, India, 2010.
AB  - Avian influenza (AI) H9N2 has been reported from poultry in India. A
      seroepidemiological study was undertaken among poultry workers to understand the
      prevalence of antibodies against AI H9N2 in Pune, Maharashtra, India. A total of
      338 poultry workers were sampled. Serum samples were tested for presence of
      antibodies against AI H9N2 virus by hemagglutination inhibition (HI) and
      microneutralization (MN) assays. A total of 249 baseline sera from general
      population from Pune were tested for antibodies against AI H9N2 and were negative
      by HI assay using >=40 cut-off antibody titre. Overall 21 subjects (21/338 =
      6.2%) were positive for antibodies against AI H9N2 by either HI or MN assays
      using >=40 cut-off antibody titre. A total of 4.7% and 3.8% poultry workers were
      positive for antibodies against AI H9N2 by HI and MN assay respectively using 40
      as cut-off antibody titre. This is the first report of seroprevalence of
      antibodies against AI H9N2 among poultry workers in India.

PMID- 22623955
TI  - The roles of dispersal, fecundity, and predation in the population persistence of
      an oak (Quercus engelmannii) under global change.
AB  - A species' response to climate change depends on the interaction of biotic and
      abiotic factors that define future habitat suitability and species' ability to
      migrate or adapt. The interactive effects of processes such as fire, dispersal,
      and predation have not been thoroughly addressed in the climate change
      literature. Our objective was to examine how life history traits, short-term
      global change perturbations, and long-term climate change interact to affect the
      likely persistence of an oak species--Quercus engelmannii (Engelmann oak).
      Specifically, we combined dynamic species distribution models, which predict
      suitable habitat, with stochastic, stage-based metapopulation models, which
      project population trajectories, to evaluate the effects of three global change
      factors--climate change, land use change, and altered fire frequency--emphasizing
      the roles of dispersal and seed predation. Our model predicted dramatic reduction
      in Q. engelmannii abundance, especially under drier climates and increased fire
      frequency. When masting lowers seed predation rates, decreased masting frequency
      leads to large abundance decreases. Current rates of dispersal are not likely to
      prevent these effects, although increased dispersal could mitigate population
      declines. The results suggest that habitat suitability predictions by themselves
      may under-estimate the impact of climate change for other species and locations.

PMID- 22623956
TI  - Bacillus licheniformis BlaR1 L3 loop is a zinc metalloprotease activated by self
      proteolysis.
AB  - In Bacillus licheniformis 749/I, BlaP beta-lactamase is induced by the presence
      of a beta-lactam antibiotic outside the cell. The first step in the induction
      mechanism is the detection of the antibiotic by the membrane-bound penicillin
      receptor BlaR1 that is composed of two functional domains: a carboxy-terminal
      domain exposed outside the cell, which acts as a penicillin sensor, and an amino
      terminal domain anchored to the cytoplasmic membrane, which works as a transducer
      transmitter. The acylation of BlaR1 sensor domain by the antibiotic generates an
      intramolecular signal that leads to the activation of the L3 cytoplasmic loop of
      the transmitter by a single-point cleavage. The exact mechanism of L3 activation
      and the nature of the secondary cytoplasmic signal launched by the activated
      transmitter remain unknown. However, these two events seem to be linked to the
      presence of a HEXXH zinc binding motif of neutral zinc metallopeptidases. By
      different experimental approaches, we demonstrated that the L3 loop binds zinc
      ion, belongs to Gluzincin metallopeptidase superfamily and is activated by self
      proteolysis.

PMID- 22623958
TI  - Classification of HIV-1 sequences using profile Hidden Markov Models.
AB  - Accurate classification of HIV-1 subtypes is essential for studying the dynamic
      spatial distribution pattern of HIV-1 subtypes and also for developing effective
      methods of treatment that can be targeted to attack specific subtypes. We propose
      a classification method based on profile Hidden Markov Model that can accurately
      identify an unknown strain. We show that a standard method that relies on the
      construction of a positive training set only, to capture unique features
      associated with a particular subtype, can accurately classify sequences belonging
      to all subtypes except B and D. We point out the drawbacks of the standard
      method; namely, an arbitrary choice of threshold to distinguish between true
      positives and true negatives, and the inability to discriminate between closely
      related subtypes. We then propose an improved classification method based on
      construction of a positive as well as a negative training set to improve
      discriminating ability between closely related subtypes like B and D. Finally, we
      show how the improved method can be used to accurately determine the subtype
      composition of Common Recombinant Forms of the virus that are made up of two or
      more subtypes. Our method provides a simple and highly accurate alternative to
      other classification methods and will be useful in accurately annotating newly
      sequenced HIV-1 strains.

PMID- 22623957
TI  - Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in
      zebrafish.
AB  - BACKGROUND: Obesity is a complex, multifactorial disorder influenced by the
      interaction of genetic, epigenetic, and environmental factors. Obesity increases
      the risk of contracting many chronic diseases or metabolic syndrome. Researchers
      have established several mammalian models of obesity to study its underlying
      mechanism. However, a lower vertebrate model for conveniently performing drug
      screening against obesity remains elusive. The specific aim of this study was to
      create a zebrafish obesity model by over expressing the insulin signaling hub of
      the Akt1 gene. METHODOLOGY/PRINCIPAL FINDINGS: Skin oncogenic transformation
      screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1)(cy18)
      displays severely obese phenotypes at the adult stage. In
      Tg(krt4:Hsa.myrAkt1)(cy18), the expression of exogenous human constitutively
      active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK
      3alpha/beta, and 70S6K. During the embryonic to larval transitory phase, the
      specific over expression of myrAkt1 in skin can promote hypertrophic and
      hyperplastic growth. From 21 hour post-fertilization (hpf) onwards, myrAkt1
      transgene was ectopically expressed in several mesenchymal derived tissues. This
      may be the result of the integration position effect. Tg(krt4:Hsa.myrAkt1)(cy18)
      caused a rapid increase of body weight, hyperplastic growth of adipocytes,
      abnormal accumulation of fat tissues, and blood glucose intolerance at the adult
      stage. Real-time RT-PCR analysis showed the majority of key genes on regulating
      adipogenesis, adipocytokine, and inflammation are highly upregulated in
      Tg(krt4:Hsa.myrAkt1)(cy18). In contrast, the myogenesis- and skeletogenesis
      related gene transcripts are significantly downregulated in
      Tg(krt4:Hsa.myrAkt1)(cy18), suggesting that excess adipocyte differentiation
      occurs at the expense of other mesenchymal derived tissues.
      CONCLUSION/SIGNIFICANCE: Collectively, the findings of this study provide direct
      evidence that Akt1 signaling plays an important role in balancing normal levels
      of fat tissue in vivo. The obese zebrafish examined in this study could be a new
      powerful model to screen novel drugs for the treatment of human obesity.

PMID- 22623959
TI  - Identification of a known mutation in Notch 3 in familiar CADASIL in China.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is an inherited disease leading to recurrent
      ischemic stroke and vascular dementia. Numerous mutations in the 23 exons of the
      NOTCH3 gene have been reported to cause CADASIL in Caucasian populations, but the
      full spectrum of genetic changes leading to this disease is yet to be known and,
      especially, very few reports are available on CADASIL in Asian populations.
      METHODS AND RESULTS: We genotyped members of a 5-generational Han Chinese family
      with CADASIL patients and identified an R133C mutation in the NOTCH3 gene.
      Clinical analysis demonstrated that the penetrance of the mutation was not
      complete. Five of the mutation carriers, not exposed to the known vascular risk
      factors, did not show any clinical feature of CADASIL, suggesting the importance
      of environmental factors to the development of this disease. CONCLUSIONS: Members
      of a 5-generational Han Chinese family with CADASIL patients had an R133C
      mutation in the NOTCH3 gene but only individuals exposed to known vascular risk
      factors developed CADASIL.

PMID- 22623960
TI  - Effects of fatty acid treatments on the dexamethasone-induced intramuscular lipid
      accumulation in chickens.
AB  - BACKGROUND: Glucocorticoid has an important effect on lipid metabolism in
      muscles, and the type of fatty acid likely affects mitochondrial utilization.
      Therefore, we hypothesize that the different fatty acid types treatment may
      affect the glucocorticoid induction of intramuscular lipid accumulation.
      METHODOLOGY/PRINCIPAL FINDINGS: The effect of dexamethasone (DEX) on fatty acid
      metabolism and storage in skeletal muscle of broiler chickens (Gallus gallus
      domesticus) was investigated with and without fatty acid treatments. Male Arbor
      Acres chickens (31 d old) were treated with either palmitic acid (PA) or oleic
      acid (OA) for 7 days, followed by DEX administration for 3 days (35-37 d old).
      The DEX-induced lipid uptake and oxidation imbalance, which was estimated by
      increased fatty acid transport protein 1 (FATP1) expression and decreased
      carnitine palmitoyl transferase 1 activity, contributed to skeletal muscle lipid
      accumulation. More sensitive than glycolytic muscle, the oxidative muscle in DEX
      treated chickens showed a decrease in the AMP to ATP ratio, a decrease in AMP
      activated protein kinase (AMPK) alpha phosphorylation and its activity, as well
      as an increase in the phosphorylation of mammalian target of rapamycin (mTOR) and
      ribosomal p70S6 kinase, without Akt activation. DEX-stimulated lipid deposition
      was augmented by PA, but alleviated by OA, in response to pathways that were
      regulated differently, including AMPK, mTOR and FATP1. CONCLUSIONS: DEX-induced
      intramuscular lipid accumulation was aggravated by SFA but alleviated by
      unsaturated fatty acid. The suppressed AMPK and augmented mTOR signaling pathways
      were involved in glucocortcoid-mediated enhanced intramuscular fat accumulation.

PMID- 22623961
TI  - Using plant functional traits to explain diversity-productivity relationships.
AB  - BACKGROUND: The different hypotheses proposed to explain positive species
      richness-productivity relationships, i.e. selection effect and complementarity
      effect, imply that plant functional characteristics are at the core of a
      mechanistic understanding of biodiversity effects. METHODOLOGY/PRINCIPAL
      FINDINGS: We used two community-wide measures of plant functional composition,
      (1) community-weighted means of trait values (CWM) and (2) functional trait
      diversity based on Rao's quadratic diversity (FD(Q)) to predict biomass
      production and measures of biodiversity effects in experimental grasslands (Jena
      Experiment) with different species richness (2, 4, 8, 16 and 60) and different
      functional group number and composition (1 to 4; legumes, grasses, small herbs,
      tall herbs) four years after establishment. Functional trait composition had a
      larger predictive power for community biomass and measures of biodiversitity
      effects (40-82% of explained variation) than species richness per se (<1-13% of
      explained variation). CWM explained a larger amount of variation in community
      biomass (80%) and net biodiversity effects (70%) than FD(Q) (36 and 38% of
      explained variation respectively). FD(Q) explained similar proportions of
      variation in complementarity effects (24%, positive relationship) and selection
      effects (28%, negative relationship) as CWM (27% of explained variation for both
      complementarity and selection effects), but for all response variables the
      combination of CWM and FD(Q) led to significant model improvement compared to a
      separate consideration of different components of functional trait composition.
      Effects of FD(Q) were mainly attributable to diversity in nutrient acquisition
      and life-history strategies. The large spectrum of traits contributing to
      positive effects of CWM on biomass production and net biodiversity effects
      indicated that effects of dominant species were associated with different trait
      combinations. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the
      identification of relevant traits and the relative impacts of functional identity
      of dominant species and functional diversity are essential for a mechanistic
      understanding of the role of plant diversity for ecosystem processes such as
      aboveground biomass production.

PMID- 22623962
TI  - Isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by
      inducing G2/m cell cycle arrest and apoptosis.
AB  - The treatment of human hepatocellular carcinoma (HCC) cell lines with (+)
      isocorydine, which was isolated and purified from Papaveraceae sp. plants,
      resulted in a growth inhibitory effect caused by the induction of G2/M phase cell
      cycle arrest and apoptosis. We report that isocorydine induces G2/M phase arrest
      by increasing cyclin B1 and p-CDK1 expression levels, which was caused by
      decreasing the expression and inhibiting the activation of Cdc25C. The
      phosphorylation levels of Chk1 and Chk2 were increased after ICD treatment.
      Furthermore, G2/M arrest induced by ICD can be disrupted by Chk1 siRNA but not by
      Chk2 siRNA. In addition, isocorydine treatment led to a decrease in the
      percentage of CD133(+) PLC/PRF/5 cells. Interestingly, isocorydine treatment
      dramatically decreased the tumorigenicity of SMMC-7721 and Huh7 cells. These
      findings indicate that isocorydine might be a potential therapeutic drug for the
      chemotherapeutic treatment of HCC.

PMID- 22623963
TI  - Intracellular electric field and pH optimize protein localization and movement.
AB  - Mammalian cell function requires timely and accurate transmission of information
      from the cell membrane (CM) to the nucleus (N). These pathways have been
      intensively investigated and many critical components and interactions have been
      identified. However, the physical forces that control movement of these proteins
      have received scant attention. Thus, transduction pathways are typically
      presented schematically with little regard to spatial constraints that might
      affect the underlying dynamics necessary for protein-protein interactions and
      molecular movement from the CM to the N. We propose messenger protein
      localization and movements are highly regulated and governed by Coulomb
      interactions between: 1. A recently discovered, radially directed E-field from
      the NM into the CM and 2. Net protein charge determined by its isoelectric point,
      phosphorylation state, and the cytosolic pH. These interactions, which are widely
      applied in elecrophoresis, provide a previously unknown mechanism for
      localization of messenger proteins within the cytoplasm as well as rapid
      shuttling between the CM and N. Here we show these dynamics optimize the speed,
      accuracy and efficiency of transduction pathways even allowing measurement of the
      location and timing of ligand binding at the CM--previously unknown components of
      intracellular information flow that are, nevertheless, likely necessary for
      detecting spatial gradients and temporal fluctuations in ligand concentrations
      within the environment. The model has been applied to the RAF-MEK-ERK pathway and
      scaffolding protein KSR1 using computer simulations and in-vitro experiments. The
      computer simulations predicted distinct distributions of phosphorylated and
      unphosphorylated components of this transduction pathway which were
      experimentally confirmed in normal breast epithelial cells (HMEC).

PMID- 22623964
TI  - What role do traditional beliefs play in treatment seeking and delay for Buruli
      ulcer disease?--insights from a mixed methods study in Cameroon.
AB  - BACKGROUND: Victims of Buruli ulcer disease (BUD) frequently report to
      specialized units at a late stage of the disease. This delay has been associated
      with local beliefs and a preference for traditional healing linked to a
      reportedly mystical origin of the disease. We assessed the role beliefs play in
      determining BUD sufferers' choice between traditional and biomedical treatments.
      METHODS: Anthropological fieldwork was conducted in community and clinical
      settings in the region of Ayos and Akonolinga in Central Cameroon. The research
      design consisted of a mixed methods study, triangulating a qualitative strand
      based on ethnographic research and quantitative data obtained through a survey
      presented to all patients at the Ayos and Akonolinga hospitals (N = 79) at the
      time of study and in four endemic communities (N = 73) belonging to the
      hospitals' catchment area. RESULTS: The analysis of BUD sufferers' health-seeking
      behaviour showed extremely complex therapeutic itineraries, including various
      attempts and failures both in the biomedical and traditional fields. Contrary to
      expectations, nearly half of all hospital patients attributed their illness to
      mystical causes, while traditional healers admitted patients they perceived to be
      infected by natural causes. Moreover, both patients in hospitals and in
      communities often combined elements of both types of treatments. Ultimately,
      perceptions regarding the effectiveness of the treatment, the option for local
      treatment as a cost prevention strategy and the characteristics of the doctor
      patient relationship were more determinant for treatment choice than beliefs.
      DISCUSSION: The ascription of delay and treatment choice to beliefs constitutes
      an over-simplification of BUD health-seeking behaviour and places the
      responsibility directly on the shoulders of BUD sufferers while potentially
      neglecting other structural elements. While more efficacious treatment in the
      biomedical sector is likely to reduce perceived mystical involvement in the
      disease, additional decentralization could constitute a key element to reduce
      delay and increase adherence to biomedical treatment.

PMID- 22623965
TI  - The cumulative effects of polymorphisms in the DNA mismatch repair genes and
      tobacco smoking in oesophageal cancer risk.
AB  - The DNA mismatch repair (MMR) enzymes repair errors in DNA that occur during
      normal DNA metabolism or are induced by certain cancer-contributing exposures. We
      assessed the association between 10 single-nucleotide polymorphisms (SNPs) in 5
      MMR genes and oesophageal cancer risk in South Africans. Prior to genotyping,
      SNPs were selected from the HapMap database, based on their significantly
      different genotypic distributions between European ancestry populations and four
      HapMap populations of African origin. In the Mixed Ancestry group, the MSH3
      rs26279 G/G versus A/A or A/G genotype was positively associated with cancer (OR
      = 2.71; 95% CI: 1.34-5.50). Similar associations were observed for PMS1 rs5742938
      (GG versus AA or AG: OR = 1.73; 95% CI: 1.07-2.79) and MLH3 rs28756991 (AA or GA
      versus GG: OR = 2.07; 95% IC: 1.04-4.12). In Black individuals, however, no
      association between MMR polymorhisms and cancer risk was observed in individual
      SNP analysis. The interactions between MMR genes were evaluated using the model
      based multifactor-dimensionality reduction approach, which showed a significant
      genetic interaction between SNPs in MSH2, MSH3 and PMS1 genes in Black and Mixed
      Ancestry subjects, respectively. The data also implies that pathogenesis of
      common polymorphisms in MMR genes is influenced by exposure to tobacco smoke. In
      conclusion, our findings suggest that common polymorphisms in MMR genes and/or
      their combined effects might be involved in the aetiology of oesophageal cancer.

PMID- 22623966
TI  - Connectivity of default-mode network is associated with cerebral edema in hepatic
      encephalopathy.
AB  - Cerebral edema, a well-known feature of acute liver disease, can occur in
      cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect
      prognosis. This study characterized and correlated functional HE abnormalities in
      the brain to cerebral edema using resting-state functional magnetic resonance
      imaging (rs-fMRI) and diffusion tensor imaging (DTI). Forty-one cirrhotic
      patients (16 without HE, 14 minimal HE, 11 overt HE) and 32 healthy controls were
      assessed. The HE grade in cirrhotic patients was evaluated by the West Haven
      criteria and neuro-psychological examinations. Functional connectivity
      correlation coefficient (fc-CC) of the default mode network (DMN) was determined
      by rs-fMRI, while the corresponding mean diffusivity (MD) was obtained from DTI.
      Correlations among inter-cortical fc-CC, DTI indices, Cognitive Ability Screening
      Instrument scores, and laboratory tests were also analyzed. Results showed that
      gradual reductions of HE-related consciousness levels, from "without HE" or
      "minimal HE" to "overt HE", correlated with decreased anterior-posterior fc-CC in
      DMN [F(4.415), p = 0.000)]. The MD values from regions with anterior-posterior fc
      CC differences in DMN revealed significant differences between the overt HE group
      and other groups. Increased MD in this network was inversely associated with
      decreased fc-CC in DMN and linearly correlated with poor cognitive performance.
      In conclusion, cerebral edema can be linked to altered cerebral temporal
      architecture that modifies both within- and between-network connectivity in HE.
      Reduced fc-CC in DMN is associated with behavior and consciousness deterioration.
      Through appropriate targets, rs-fMRI technology may provide relevant supplemental
      information for monitoring HE and serve as a new biomarker for clinical
      diagnosis.

PMID- 22623967
TI  - CRISPR typing and subtyping for improved laboratory surveillance of Salmonella
      infections.
AB  - Laboratory surveillance systems for salmonellosis should ideally be based on the
      rapid serotyping and subtyping of isolates. However, current typing methods are
      limited in both speed and precision. Using 783 strains and isolates belonging to
      130 serotypes, we show here that a new family of DNA repeats named CRISPR
      (clustered regularly interspaced short palindromic repeats) is highly polymorphic
      in Salmonella. We found that CRISPR polymorphism was strongly correlated with
      both serotype and multilocus sequence type. Furthermore, spacer microevolution
      discriminated between subtypes within prevalent serotypes, making it possible to
      carry out typing and subtyping in a single step. We developed a high-throughput
      subtyping assay for the most prevalent serotype, Typhimurium. An open web
      accessible database was set up, providing a serotype/spacer dictionary and an
      international tool for strain tracking based on this innovative, powerful typing
      and subtyping tool.

PMID- 22623968
TI  - A scalable system for production of functional pancreatic progenitors from human
      embryonic stem cells.
AB  - Development of a human embryonic stem cell (hESC)-based therapy for type 1
      diabetes will require the translation of proof-of-principle concepts into a
      scalable, controlled, and regulated cell manufacturing process. We have
      previously demonstrated that hESC can be directed to differentiate into
      pancreatic progenitors that mature into functional glucose-responsive, insulin
      secreting cells in vivo. In this study we describe hESC expansion and banking
      methods and a suspension-based differentiation system, which together underpin an
      integrated scalable manufacturing process for producing pancreatic progenitors.
      This system has been optimized for the CyT49 cell line. Accordingly, qualified
      large-scale single-cell master and working cGMP cell banks of CyT49 have been
      generated to provide a virtually unlimited starting resource for manufacturing.
      Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent
      culture format that achieves 50-100 fold expansion per week. Undifferentiated
      CyT49 were then aggregated into clusters in dynamic rotational suspension
      culture, followed by differentiation en masse for two weeks with a four-stage
      protocol. Numerous scaled differentiation runs generated reproducible and defined
      population compositions highly enriched for pancreatic cell lineages, as shown by
      examining mRNA expression at each stage of differentiation and flow cytometry of
      the final population. Islet-like tissue containing glucose-responsive, insulin
      secreting cells was generated upon implantation into mice. By four- to five
      months post-engraftment, mature neo-pancreatic tissue was sufficient to protect
      against streptozotocin (STZ)-induced hyperglycemia. In summary, we have developed
      a tractable manufacturing process for the generation of functional pancreatic
      progenitors from hESC on a scale amenable to clinical entry.

PMID- 22623969
TI  - Virulence characteristic and MLST-agr genetic background of high-level mupirocin
      resistant, MRSA isolates from Shanghai and Wenzhou, China.
AB  - The emergence and prevalence of high-level mupirocin-resistant, methicillin
      resistant Staphylococcus aureus (MuH MRSA) is challenging the eradication of MRSA
      nasal carriage and the treatment of skin and soft tissue infections. To
      understand the potentially pathogenetic capacity and the genetic basis of MuH
      MRSA, it is important to have a detailed knowledge of the molecular traits of
      this organism. Fifty three MuH MRSA isolates were gathered from Shanghai (28
      isolates) and Wenzhou (25 isolates) in China. These isolates, consisting of 27
      different PFGE-SCCmec-spa patterns, were examined by PCR for 35 virulence genes
      and further typed using agr (accessory gene regulator) typing and MLST
      (multilocus sequence typing). All 53 strains were positive for the genes hlg/hlg
      variant and icaD, and negative for seb, sed, see, seh, eta, etb, hld, cap-5, and
      ACME-arcA. Compared with Wenzhou isolates, Shanghai isolates were more likely to
      carry seg (P = 0.002) and several other genes which were not found in Wenzhou
      strains such as sec, sei, tst (P<0.001 each), and pvl (P = 0.012), and less
      likely to contain sea (P<0.001), cna (P = 0.031), and efb (P = 0.045). MLST and
      agr typing showed that ST239-agr1, ST5-agr1, and ST239-agr2 were the common
      lineages in MuH MRSA isolates from these two different regions. Our results
      indicated that MuH MRSA strains from two different geographic regions of China
      have differences in distribution of some virulence genes, while their major MLST
      agr genetic backgrounds were accordant.

PMID- 22623970
TI  - A game-theoretic model of interactions between Hibiscus latent Singapore virus
      and tobacco mosaic virus.
AB  - Mixed virus infections in plants are common in nature and their interactions
      affecting host plants would depend mainly on plant species, virus strains, the
      order of infection and initial amount of inoculum. Hence, the prediction of
      outcome of virus competition in plants is not easy. In this study, we applied
      evolutionary game theory to model the interactions between Hibiscus latent
      Singapore virus (HLSV) and Tobacco mosaic virus (TMV) in Nicotiana benthamiana
      under co-infection in a plant host. The accumulation of viral RNA was quantified
      using qPCR at 1, 2 and 8 days post infection (dpi), and two different methods
      were employed to predict the dominating virus. TMV was predicted to dominate the
      game in the long run and this prediction was confirmed by both qRT-PCR at 8 dpi
      and the death of co-infected plants after 15 dpi. In addition, we validated our
      model by using data reported in the literature. Ten out of fourteen reported co
      infection outcomes agreed with our predictions. Explanations were given for the
      four interactions that did not agree with our model. Hence, it serves as a
      valuable tool in making long term predictions using short term data obtained in
      virus co-infections.

PMID- 22623971
TI  - Vasoactive intestinal peptide and its receptors in human ovarian cortical
      follicles.
AB  - BACKGROUND: Ovarian cryopreservation is one option for fertility preservation in
      patients with cancer. The danger of reseeding malignancies could be eliminated by
      in vitro maturation of primordial follicles from the frozen-thawed tissue.
      However, the development of this system is hindered by uncertainties regarding
      factors that activate primordial follicles. Neuronal growth factors such as
      vasoactive intestinal peptide (VIP) play important roles in early mammalian
      folliculogenesis. There are no data on the expression of VIP and its vasoactive
      intestinal peptide pituitary adenylate cyclase 1 and 2 receptors (VPAC1-R and
      VPAC2-R) in human preantral follicles. METHODOLOGY/PRINCIPAL FINDINGS: Tissue
      samples from 14 human fetal ovaries and 40 ovaries from girls/women were prepared
      to test for the expression of VIP, VPAC1-R, and VPAC2-R on the protein
      (immunohistochemisty) and mRNA (reverse transcription polymerase chain reaction)
      levels. Immunohistochemistry staining was mostly weak, especially in fetal
      samples. The VIP protein was identified in oocytes and granulosa cells (GCs) in
      the fetal samples from 22 gestational weeks (GW) onwards. In girls/women, VIP
      follicular staining (oocytes and GCs) was identified in 45% of samples. VPAC1-R
      protein was identified in follicles in all fetal samples from 22GW onwards and in
      63% of the samples from girls/women (GC staining only in 40%). VPAC2-R protein
      was identified in follicles in 33% of fetal samples and 47% of the samples from
      girls/women. The mRNA transcripts for VIP, VPAC1-R, and VPAC2-R were identified
      in ovarian extracts from fetuses and women. CONCLUSIONS: VIP and its two
      receptors are expressed in human ovarian preantral follicles. However, their weak
      staining suggests they have limited roles in early follicular growth. To
      elucidate if VIP activates human primordial follicles, it should be added to the
      culture medium.

PMID- 22623973
TI  - An improved PSO algorithm for generating protective SNP barcodes in breast
      cancer.
AB  - BACKGROUND: Possible single nucleotide polymorphism (SNP) interactions in breast
      cancer are usually not investigated in genome-wide association studies.
      Previously, we proposed a particle swarm optimization (PSO) method to compute
      these kinds of SNP interactions. However, this PSO does not guarantee to find the
      best result in every implement, especially when high-dimensional data is
      investigated for SNP-SNP interactions. METHODOLOGY/PRINCIPAL FINDINGS: In this
      study, we propose IPSO algorithm to improve the reliability of PSO for the
      identification of the best protective SNP barcodes (SNP combinations and
      genotypes with maximum difference between cases and controls) associated with
      breast cancer. SNP barcodes containing different numbers of SNPs were computed.
      The top five SNP barcode results are retained for computing the next SNP barcode
      with a one-SNP-increase for each processing step. Based on the simulated data for
      23 SNPs of six steroid hormone metabolisms and signalling-related genes, the
      performance of our proposed IPSO algorithm is evaluated. Among 23 SNPs, 13 SNPs
      displayed significant odds ratio (OR) values (1.268 to 0.848; p<0.05) for breast
      cancer. Based on IPSO algorithm, the jointed effect in terms of SNP barcodes with
      two to seven SNPs show significantly decreasing OR values (0.84 to 0.57; p<0.05
      to 0.001). Using PSO algorithm, two to four SNPs show significantly decreasing OR
      values (0.84 to 0.77; p<0.05 to 0.001). Based on the results of 20 simulations,
      medians of the maximum differences for each SNP barcode generated by IPSO are
      higher than by PSO. The interquartile ranges of the boxplot, as well as the upper
      and lower hinges for each n-SNP barcode (n = 3~10) are more narrow in IPSO than
      in PSO, suggesting that IPSO is highly reliable for SNP barcode identification.
      CONCLUSIONS/SIGNIFICANCE: Overall, the proposed IPSO algorithm is robust to
      provide exact identification of the best protective SNP barcodes for breast
      cancer.

PMID- 22623972
TI  - Gut pathology and responses to the microsporidium Nosema ceranae in the honey bee
      Apis mellifera.
AB  - The microsporidium Nosema ceranae is a newly prevalent parasite of the European
      honey bee (Apis mellifera). Although this parasite is presently spreading across
      the world into its novel host, the mechanisms by it which affects the bees and
      how bees respond are not well understood. We therefore performed an extensive
      characterization of the parasite effects at the molecular level by using genetic
      and biochemical tools. The transcriptome modifications at the midgut level were
      characterized seven days post-infection with tiling microarrays. Then we tested
      the bee midgut response to infection by measuring activity of antioxidant and
      detoxification enzymes (superoxide dismutases, glutathione peroxidases,
      glutathione reductase, and glutathione-S-transferase). At the gene-expression
      level, the bee midgut responded to N. ceranae infection by an increase in
      oxidative stress concurrent with the generation of antioxidant enzymes, defense
      and protective response specifically observed in the gut of mammals and insects.
      However, at the enzymatic level, the protective response was not confirmed, with
      only glutathione-S-transferase exhibiting a higher activity in infected bees. The
      oxidative stress was associated with a higher transcription of sugar transporter
      in the gut. Finally, a dramatic effect of the microsporidia infection was the
      inhibition of genes involved in the homeostasis and renewal of intestinal tissues
      (Wnt signaling pathway), a phenomenon that was confirmed at the histological
      level. This tissue degeneration and prevention of gut epithelium renewal may
      explain early bee death. In conclusion, our integrated approach not only gives
      new insights into the pathological effects of N. ceranae and the bee gut
      response, but also demonstrate that the honey bee gut is an interesting model
      system for studying host defense responses.

PMID- 22623974
TI  - A novel generalized normal distribution for human longevity and other negatively
      skewed data.
AB  - Negatively skewed data arise occasionally in statistical practice; perhaps the
      most familiar example is the distribution of human longevity. Although other
      generalizations of the normal distribution exist, we demonstrate a new
      alternative that apparently fits human longevity data better. We propose an
      alternative approach of a normal distribution whose scale parameter is
      conditioned on attained age. This approach is consistent with previous findings
      that longevity conditioned on survival to the modal age behaves like a normal
      distribution. We derive such a distribution and demonstrate its accuracy in
      modeling human longevity data from life tables. The new distribution is
      characterized by 1. An intuitively straightforward genesis; 2. Closed forms for
      the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non
      statisticians, based on its close relationship to the normal distribution.

PMID- 22623975
TI  - Roles of molecular layer interneurons in sensory information processing in mouse
      cerebellar cortex Crus II in vivo.
AB  - BACKGROUND: Cerebellar cortical molecular layer interneurons (MLIs) play
      essential roles in sensory information processing by the cerebellar cortex.
      However, recent experimental and modeling results are questioning traditional
      roles for molecular layer inhibition in the cerebellum. METHODS AND MAIN RESULTS:
      Synaptic responses of MLIs and Purkinje cells (PCs), evoked by air-puff
      stimulation of the ipsilateral whisker pad were recorded from cerebellar cortex
      Crus II in urethane-anesthetized ICR mice by in vivo whole-cell patch-clamp
      recording techniques. Under current-clamp (I = 0), air-puff stimuli were found to
      primarily produce inhibition in PCs. In MLIs, this stimulus evoked spike firing
      regardless of whether they made basket-type synaptic connections or not. However,
      MLIs not making basket-type synaptic connections had higher rates of background
      activity and also generated spontaneous spike-lets. Under voltage-clamp
      conditions, excitatory postsynaptic currents (EPSCs) were recorded in MLIs,
      although the predominant response of recorded PCs was an inhibitory postsynaptic
      potential (IPSP). The latencies of EPSCs were similar for all MLIs, but the time
      course and amplitude of EPSCs varied with depth in the molecular layer. The
      highest amplitude, shortest duration EPSCs were recorded from MLIs deep in the
      molecular layer, which also made basket-type synaptic connections. Comparing MLI
      to PC responses, time to peak of PC IPSP was significantly slower than MLI
      recorded EPSCs. Blocking GABA(A) receptors uncovered larger EPSCs in PCs whose
      time to peak, half-width and 10-90% rising time were also significantly slower
      than in MLIs. Biocytin labeling indicated that the MLIs (but not PCs) are dye
      coupled. CONCLUSIONS: These findings indicate that tactile face stimulation
      evokes rapid excitation in MLIs and inhibition occurring at later latencies in
      PCs in mouse cerebellar cortex Crus II. These results support previous
      suggestions that the lack of parallel fiber driven PC activity is due to the
      effect of MLI inhibition.

PMID- 22623976
TI  - Socio-economic inequalities in the use of postnatal care in India.
AB  - OBJECTIVES: First, our objective was to estimate socio-economic inequalities in
      the use of postnatal care (PNC) compared with those in the use of care at birth
      and antenatal care. Second, we wanted to compare inequalities in the use of PNC
      between facility births and home births and to determine inequalities in the use
      of PNC among mothers with high-risk births. METHODS AND FINDINGS: Rich-poor
      ratios and concentration indices for maternity care were estimated using the
      third round of the District Level Household Survey conducted in India in 2007-08.
      Binary logistic regression models were used to examine the socio-economic
      inequalities associated with use of PNC after adjusting for relevant socio
      economic and demographic characteristics. PNC for both mothers and newborns was
      substantially lower than the care received during pregnancy and child birth. Only
      44% of mothers in India at the time of survey received any care within 48 hours
      after birth. Likewise, only 45% of newborns received check-up within 24 hours of
      birth. Mothers who had home births were significantly less likely to have
      received PNC than those who had facility births, with significant differences
      across the socio-economic strata. Moreover, the rich-poor gap in PNC use was
      significantly wider for mothers with birth complications. CONCLUSIONS: PNC use
      has been unacceptably low in India given the risks of mortality for mothers and
      babies shortly after birth. However, there is evidence to suggest that effective
      use of pregnancy and childbirth care in health facilities led to better PNC.
      There are also significant socio-economic inequalities in access to PNC even for
      those accessing facility-based care. The coverage of essential PNC is inadequate,
      especially for mothers from economically disadvantaged households. The findings
      suggest the need for strengthening PNC services to keep pace with advances in
      coverage for care at birth and prenatal services in India through targeted policy
      interventions.

PMID- 22623977
TI  - Involvement of microRNA lethal-7a in the regulation of embryo implantation in
      mice.
AB  - MicroRNAs interact with multiple mRNAs resulting in their degradation and/or
      translational repression. This report used the delayed implantation model to
      determine the role of miRNAs in blastocysts. Dormant blastocysts in delayed
      implanting mice were activated by estradiol. Differential expression of 45 out of
      238 miRNAs examined was found between the dormant and the activated blastocysts.
      Five of the nine members of the microRNA lethal-7 (let-7) family were down
      regulated after activation. Human blastocysts also had a low expression of let-7
      family. Forced-expression of a family member, let-7a in mouse blastocysts
      decreased the number of implantation sites (let-7a: 1.1+/-0.4; control: 3.8+/
      0.4) in vivo, and reduced the percentages of blastocyst that attached (let-7a:
      42.0+/-8.3%; control: 79.0+/-5.1%) and spreaded (let-7a: 33.5+/-2.9%; control:
      67.3+/-3.8%) on fibronectin in vitro. Integrin-beta3, a known implantation
      related molecule, was demonstrated to be a target of let-7a by 3'-untranslated
      region reporter assay in cervical cancer cells HeLa, and Western blotting in
      mouse blastocysts. The inhibitory effect of forced-expression of let-7a on
      blastocyst attachment and outgrowth was partially nullified in vitro and in vivo
      by forced-expression of integrin-beta3. This study provides the first direct
      evidence that let-7a is involved in regulating the implantation process partly
      via modulation of the expression of integrin-beta3.

PMID- 22623978
TI  - A replication study of GWAS-derived lipid genes in Asian Indians: the chromosomal
      region 11q23.3 harbors loci contributing to triglycerides.
AB  - Recent genome-wide association scans (GWAS) and meta-analysis studies on European
      populations have identified many genes previously implicated in lipid regulation.
      Validation of these loci on different global populations is important in
      determining their clinical relevance, particularly for development of novel drug
      targets for treating and preventing diabetic dyslipidemia and coronary artery
      disease (CAD). In an attempt to replicate GWAS findings on a non-European sample,
      we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B
      rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4
      C2 rs4420638) in our Asian Indian cohort from the Sikh Diabetes Study (SDS)
      comprising 3,781 individuals (2,902 from Punjab and 879 from the US). Two of the
      six SNPs examined showed convincing replication in these populations of Asian
      Indian origin. Our study confirmed a strong association of CETP rs3764261 with
      high-density lipoprotein cholesterol (HDL-C) (p = 2.03*10(-26)). Our results also
      showed significant associations of two GWAS SNPs (rs964184 and rs12286037) from
      BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG) levels in this
      Asian Indian cohort (rs964184: p = 1.74*10(-17); rs12286037: p = 1.58*10(-2)). We
      further explored 45 SNPs in a ~195 kb region within the chromosomal region
      11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes) in 8,530
      Asian Indians from the London Life Sciences Population (LOLIPOP) (UK) and SDS
      cohorts. Five more SNPs revealed significant associations with TG in both cohorts
      individually as well as in a joint meta-analysis. However, the strongest signal
      for TG remained with BUD13-ZNF259 (rs964184: p = 1.06*10(-39)). Future targeted
      deep sequencing and functional studies should enhance our understanding of the
      clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG)
      and, consequently, diabetes and CAD.

PMID- 22623980
TI  - LsrR-mediated quorum sensing controls invasiveness of Salmonella typhimurium by
      regulating SPI-1 and flagella genes.
AB  - Bacterial cell-to-cell communication, termed quorum sensing (QS), controls
      bacterial behavior by using various signal molecules. Despite the fact that the
      LuxS/autoinducer-2 (AI-2) QS system is necessary for normal expression of
      Salmonella pathogenicity island-1 (SPI-1), the mechanism remains unknown. Here,
      we report that the LsrR protein, a transcriptional regulator known to be involved
      in LuxS/AI-2-mediated QS, is also associated with the regulation of SPI-1
      mediated Salmonella virulence. We determined that LsrR negatively controls SPI-1
      and flagella gene expressions. As phosphorylated AI-2 binds to and inactivates
      LsrR, LsrR remains active and decreases expression of SPI-1 and flagella genes in
      the luxS mutant. The reduced expression of those genes resulted in impaired
      invasion of Salmonella into epithelial cells. Expression of SPI-1 and flagella
      genes was also reduced by overexpression of the LsrR regulator from a plasmid,
      but was relieved by exogenous AI-2, which binds to and inactivates LsrR. These
      results imply that LsrR plays an important role in selecting infectious niche of
      Salmonella in QS dependent mode.

PMID- 22623979
TI  - Inactivation of CDK/pRb pathway normalizes survival pattern of lymphoblasts
      expressing the FTLD-progranulin mutation c.709-1G>A.
AB  - BACKGROUND: Mutations in the progranulin (PGRN) gene, leading to
      haploinsufficiency, cause familial frontotemporal lobar degeneration (FTLD-TDP),
      although the pathogenic mechanism of PGRN deficit is largely unknown. Allelic
      loss of PGRN was previously shown to increase the activity of cyclin-dependent
      kinase (CDK) CDK6/pRb pathway in lymphoblasts expressing the c.709-1G>A PGRN
      mutation. Since members of the CDK family appear to play a role in
      neurodegenerative disorders and in apoptotic death of neurons subjected to
      various insults, we investigated the role of CDK6/pRb in cell survival/death
      mechanisms following serum deprivation. METHODOLOGY/PRINCIPAL FINDINGS: We
      performed a comparative study of cell viability after serum withdrawal of
      established lymphoblastoid cell lines from control and carriers of c.709-1G>A
      PGRN mutation, asymptomatic and FTLD-TDP diagnosed individuals. Our results
      suggest that the CDK6/pRb pathway is enhanced in the c.709-1G>A bearing
      lymphoblasts. Apparently, this feature allows PGRN-deficient cells to escape from
      serum withdrawal-induced apoptosis by decreasing the activity of executive
      caspases and lowering the dissipation of mitochondrial membrane potential and the
      release of cytochrome c from the mitochondria. Inhibitors of CDK6 expression
      levels like sodium butyrate or the CDK6 activity such as PD332991 were able to
      restore the vulnerability of lymphoblasts from FTLD-TDP patients to trophic
      factor withdrawal. CONCLUSION/SIGNIFICANCE: The use of PGRN-deficient
      lymphoblasts from FTLD-TDP patients may be a useful model to investigate cell
      biochemical aspects of this disease. It is suggested that CDK6 could be
      potentially a therapeutic target for the treatment of the FTLD-TDP.

PMID- 22623981
TI  - Detailed structural analysis of lipids directly on tissue specimens using a MALDI
      SpiralTOF-Reflectron TOF mass spectrometer.
AB  - Direct tissue analysis using a novel tandem time-of-flight (TOF-TOF) mass
      spectrometer is described. This system consists of a matrix-assisted laser
      desorption/ionization ion source, a spiral ion trajectory TOF mass spectrometer
      "SpiralTOF (STOF)", a collision cell, and an offset parabolic reflectron (RTOF).
      The features of this system are high precursor ion selectivity due to a 17-m
      flight path length in STOF and elimination of post-source decay (PSD) ions. The
      acceleration energy is 20 keV, so that high-energy collision-induced dissociation
      (HE-CID) is possible. Elimination of PSD ions allows observation of the product
      ions inherent to the HE-CID process. By using this tandem TOF instrument, the
      product ion spectrum of lipids provided detailed structural information of fatty
      acid residues.

PMID- 22623982
TI  - Modelling the spatio-temporal cell dynamics reveals novel insights on cell
      differentiation and proliferation in the small intestinal crypt.
AB  - We developed a slow structural relaxation model to describe cellular dynamics in
      the crypt of the mouse small intestine. Cells are arranged in a three dimensional
      spiral the size of which dynamically changes according to cell production demands
      of adjacent villi. Cell differentiation and proliferation is regulated through
      Wnt and Notch signals, the strength of which depends on the local cell
      composition. The highest level of Wnt activity is associated with maintaining
      equipotent stem cells (SC), Paneth cells and common goblet-Paneth cell
      progenitors (CGPCPs) intermingling at the crypt bottom. Low levels of Wnt
      signalling area are associated with stem cells giving rise to secretory cells
      (CGPCPs, enteroendocrine or Tuft cells) and proliferative absorptive progenitors.
      Deciding between these two fates, secretory and stem/absorptive cells, depends on
      Notch signalling. Our model predicts that Notch signalling inhibits secretory
      fate if more than 50% of cells they are in contact with belong to the secretory
      lineage. CGPCPs under high Wnt signalling will differentiate into Paneth cells
      while those migrating out from the crypt bottom differentiate into goblet cells.
      We have assumed that mature Paneth cells migrating upwards undergo anoikis.
      Structural relaxation explains the localisation of Paneth cells to the crypt
      bottom in the absence of active forces. The predicted crypt generation time from
      one SC is 4-5 days with 10-12 days needed to reach a structural steady state. Our
      predictions are consistent with experimental observations made under altered Wnt
      and Notch signalling. Mutations affecting stem cells located at the crypt floor
      have a 50% chance of being propagated throughout the crypt while mutations in
      cells above are rarely propagated. The predicted recovery time of an injured
      crypt losing half of its cells is approximately 2 days.

PMID- 22623983
TI  - Daily rhythms of plasma melatonin, but not plasma leptin or leptin mRNA, vary
      between lean, obese and type 2 diabetic men.
AB  - Melatonin and leptin exhibit daily rhythms that may contribute towards changes in
      metabolic physiology. It remains unclear, however, whether this rhythmicity is
      altered in obesity or type 2 diabetes (T2DM). We tested the hypothesis that 24
      hour profiles of melatonin, leptin and leptin mRNA are altered by metabolic
      status in laboratory conditions. Men between 45-65 years old were recruited into
      lean, obese-non-diabetic or obese-T2DM groups. Volunteers followed strict sleep
      wake and dietary regimes for 1 week before the laboratory study. They were then
      maintained in controlled light-dark conditions, semi-recumbent posture and fed
      hourly iso-energetic drinks during wake periods. Hourly blood samples were
      collected for hormone analysis. Subcutaneous adipose biopsies were collected 6
      hourly for gene expression analysis. Although there was no effect of subject
      group on the timing of dim light melatonin onset (DLMO), nocturnal plasma
      melatonin concentration was significantly higher in obese-non-diabetic subjects
      compared to weight-matched T2DM subjects (p<0.01) and lean controls (p<0.05). Two
      T2DM subjects failed to produce any detectable melatonin, although did exhibit
      plasma cortisol rhythms comparable to others in the group. Consistent with the
      literature, there was a significant (p<0.001) effect of subject group on absolute
      plasma leptin concentration and, when expressed relative to an individual's 24
      hour mean, plasma leptin showed significant (p<0.001) diurnal variation. However,
      there was no difference in amplitude or timing of leptin rhythms between
      experimental groups. There was also no significant effect of time on leptin mRNA
      expression. Despite an overall effect (p<0.05) of experimental group, post-hoc
      analysis revealed no significant pair-wise effects of group on leptin mRNA
      expression. Altered plasma melatonin rhythms in weight-matched T2DM and non
      diabetic individuals supports a possible role of melatonin in T2DM aetiology.
      However, neither obesity nor T2DM changed 24-hour rhythms of plasma leptin
      relative to cycle mean, or expression of subcutaneous adipose leptin gene
      expression, compared with lean subjects.

PMID- 22623984
TI  - Deep sequencing of small RNAs in tomato for virus and viroid identification and
      strain differentiation.
AB  - Small RNAs (sRNA), including microRNAs (miRNA) and small interfering RNAs
      (siRNA), are produced abundantly in plants and animals and function in regulating
      gene expression or in defense against virus or viroid infection. Analysis of
      siRNA profiles upon virus infection in plant may allow for virus identification,
      strain differentiation, and de novo assembly of virus genomes. In the present
      study, four suspected virus-infected tomato samples collected in the U.S. and
      Mexico were used for sRNA library construction and deep sequencing. Each library
      generated between 5-7 million sRNA reads, of which more than 90% were from the
      tomato genome. Upon in-silico subtraction of the tomato sRNAs, the remaining
      highly enriched, virus-like siRNA pools were assembled with or without reference
      virus or viroid genomes. A complete genome was assembled for Potato spindle tuber
      viroid (PSTVd) using siRNA alone. In addition, a near complete virus genome (98%)
      also was assembled for Pepino mosaic virus (PepMV). A common mixed infection of
      two strains of PepMV (EU and US1), which shared 82% of genome nucleotide sequence
      identity, also could be differentially assembled into their respective genomes.
      Using de novo assembly, a novel potyvirus with less than 60% overall genome
      nucleotide sequence identity to other known viruses was discovered and its full
      genome sequence obtained. Taken together, these data suggest that the sRNA deep
      sequencing technology will likely become an efficient and powerful generic tool
      for virus identification in plants and animals.

PMID- 22623985
TI  - Cell wall trapping of autocrine peptides for human G-protein-coupled receptors on
      the yeast cell surface.
AB  - G-protein-coupled receptors (GPCRs) regulate a wide variety of physiological
      processes and are important pharmaceutical targets for drug discovery. Here, we
      describe a unique concept based on yeast cell-surface display technology to
      selectively track eligible peptides with agonistic activity for human GPCRs (Cell
      Wall Trapping of Autocrine Peptides (CWTrAP) strategy). In our strategy,
      individual recombinant yeast cells are able to report autocrine-positive activity
      for human GPCRs by expressing a candidate peptide fused to an anchoring motif.
      Following expression and activation, yeast cells trap autocrine peptides onto
      their cell walls. Because captured peptides are incapable of diffusion, they have
      no impact on surrounding yeast cells that express the target human GPCR and non
      signaling peptides. Therefore, individual yeast cells can assemble the autonomous
      signaling complex and allow single-cell screening of a yeast population. Our
      strategy may be applied to identify eligible peptides with agonistic activity for
      target human GPCRs.

PMID- 22623986
TI  - In vivo evolution of tumor-derived endothelial cells.
AB  - The growth of a malignant tumor beyond a certain, limited size requires that it
      first develop an independent blood supply. In addition to providing metabolic
      support, this neovasculature also allows tumor cells to access the systemic
      circulation, thus facilitating metastatic dissemination. The neovasculature may
      originate either from normal blood vessels in close physical proximity to the
      tumor and/or from the recruitment of bone marrow-derived endothelial cell (EC)
      precursors. Recent studies have shown that human tumor vasculature ECs may also
      arise directly from tumor cells themselves and that the two populations have
      highly similar or identical karyotypes. We now show that, during the course of
      serial in vivo passage, these tumor-derived ECs (TDECs) progressively acquire
      more pronounced EC-like properties. These include higher-level expression of EC
      specific genes and proteins, a greater capacity for EC-like behavior in vitro,
      and a markedly enhanced propensity to incorporate into the tumor vasculature. In
      addition, both vessel density and size are significantly increased in neoplasms
      derived from mixtures of tumor cells and serially passaged TDECs. A comparison of
      early- and late-passage TDECs using whole-genome single nucleotide polymorphism
      profiling showed the latter cells to have apparently evolved by a process of
      clonal expansion of a population with a distinct pattern of interstitial
      chromosomal gains and losses affecting a relatively small number of genes. The
      majority of these have established roles in vascular development, tumor
      suppression or epithelial-mesenchymal transition. These studies provide direct
      evidence that TDECs have a strong evolutionary capacity as a result of their
      inherent genomic instability. Consequently such cells might be capable of
      escaping anti-angiogenic cancer therapies by generating resistant populations.

PMID- 22623987
TI  - Multiple miscarriages are associated with the risk of ovarian cancer: results
      from the European Prospective Investigation into Cancer and Nutrition.
AB  - While the risk of ovarian cancer clearly reduces with each full-term pregnancy,
      the effect of incomplete pregnancies is unclear. We investigated whether
      incomplete pregnancies (miscarriages and induced abortions) are associated with
      risk of epithelial ovarian cancer. This observational study was carried out in
      female participants of the European Prospective Investigation into Cancer and
      Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010.
      The baseline questionnaire elicited information on miscarriages and induced
      abortions, reproductive history, and lifestyle-related factors. During a median
      follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial
      ovarian cancer. Despite the lack of an overall association (ever vs. never), risk
      of ovarian cancer was higher among women with multiple incomplete pregnancies
      (HR(>=4vs.0): 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23).
      This association was particularly evident for multiple miscarriages (HR(>=4vs.0):
      1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no
      significant association for multiple induced abortions (HR(>=4vs.0): 1.46, 95%
      CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest
      that multiple miscarriages are associated with an increased risk of epithelial
      ovarian cancer, possibly through a shared cluster of etiological factors or a
      common underlying pathology. These findings should be interpreted with caution as
      this is the first study to show this association and given the small number of
      cases in the highest exposure categories.

PMID- 22623988
TI  - Mitochondrial and plasma membrane pools of stomatin-like protein 2 coalesce at
      the immunological synapse during T cell activation.
AB  - Stomatin-like protein 2 (SLP-2) is a member of the stomatin-prohibitin-flotillin
      HflC/K (SPFH) superfamily. Recent evidence indicates that SLP-2 is involved in
      the organization of cardiolipin-enriched microdomains in mitochondrial membranes
      and the regulation of mitochondrial biogenesis and function. In T cells, this
      role translates into enhanced T cell activation. Although the major pool of SLP-2
      is associated with mitochondria, we show here that there is an additional pool of
      SLP-2 associated with the plasma membrane of T cells. Both plasma membrane
      associated and mitochondria-associated pools of SLP-2 coalesce at the
      immunological synapse (IS) upon T cell activation. SLP-2 is not required for
      formation of IS nor for the re-localization of mitochondria to the IS because SLP
      2-deficient T cells showed normal re-localization of these organelles in response
      to T cell activation. Interestingly, upon T cell activation, we found the surface
      pool of SLP-2 mostly excluded from the central supramolecular activation complex,
      and enriched in the peripheral area of the IS where signalling TCR microclusters
      are located. Based on these results, we propose that SLP-2 facilitates the
      compartmentalization not only of mitochondrial membranes but also of the plasma
      membrane into functional microdomains. In this latter location, SLP-2 may
      facilitate the optimal assembly of TCR signalosome components. Our data also
      suggest that there may be a net exchange of membrane material between
      mitochondria and plasma membrane, explaining the presence of some mitochondrial
      proteins in the plasma membrane.

PMID- 22623989
TI  - Stromal cell-derived factor 1 regulates the actin organization of chondrocytes
      and chondrocyte hypertrophy.
AB  - Stromal cell-derived factor 1 (SDF-1/CXCL12/PBSF) plays important roles in the
      biological and physiological functions of haematopoietic and mesenchymal stem
      cells. This chemokine regulates the formation of multiple organ systems during
      embryogenesis. However, its roles in skeletal development remain unclear. Here we
      investigated the roles of SDF-1 in chondrocyte differentiation. We demonstrated
      that SDF-1 protein was expressed at pre-hypertrophic and hypertrophic
      chondrocytes in the newly formed endochondral callus of rib fracture as well as
      in the growth plate of normal mouse tibia by immunohistochemical analysis. Using
      SDF-1(-/-) mouse embryo, we histologically showed that the total length of the
      whole humeri of SDF-1(-/-) mice was significantly shorter than that of wild-type
      mice, which was contributed mainly by shorter hypertrophic and calcified zones in
      SDF-1(-/-) mice. Actin cytoskeleton of hypertrophic chondrocytes in SDF-1(-/-)
      mouse humeri showed less F-actin and rounder shape than that of wild-type mice.
      Primary chondrocytes from SDF-1(-/-) mice showed the enhanced formation of
      philopodia and loss of F-actin. The administration of SDF-1 to primary
      chondrocytes of wild-type mice and SDF-1(-/-) mice promoted the formation of
      actin stress fibers. Organ culture of embryonic metatarsals from SDF-1(-/-) mice
      showed the growth delay, which was recovered by an exogenous administration of
      SDF-1. mRNA expression of type X collagen in metatarsals and in primary
      chondrocytes of SDF-1(-/-) mouse embryo was down-regulated while the
      administration of SDF-1 to metatarsals recovered. These data suggests that SDF-1
      regulates the actin organization and stimulates bone growth by mediating
      chondrocyte hypertrophy.

PMID- 22623990
TI  - A novel recombinant Peste des petits ruminants-canine adenovirus vaccine elicits
      long-lasting neutralizing antibody response against PPR in goats.
AB  - BACKGROUND: Peste des petits ruminants (PPR) is a highly contagious infectious
      disease of goats, sheep and small wild ruminant species with high morbidity and
      mortality rates. The Peste des petits ruminants virus (PPRV) expresses a
      hemagglutinin (H) glycoprotein on its outer envelope that is crucial for viral
      attachment to host cells and represents a key antigen for inducing the host
      immune response. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether H can be
      exploited to generate an effective PPRV vaccine, a replication-competent
      recombinant canine adenovirus type-2 (CAV-2) expressing the H gene of PPRV
      (China/Tibet strain) was constructed by the in vitro ligation method. The H
      expression cassette, including the human cytomegalovirus (hCMV) promoter/enhancer
      and the BGH early mRNA polyadenylation signal, was inserted into the SspI site of
      the E3 region, which is not essential for proliferation of CAV-2. Infectious
      recombinant rCAV-2-PPRV-H virus was generated in transfected MDCK cells and used
      to immunize goats. All vaccinated animals produced antibodies upon primary
      injection that were effective in neutralizing PPRV in vitro. Higher antibody
      titer was obtained following booster inoculation, and the antibody was detectable
      in goats for at least seven months. No serious recombinant virus-related adverse
      effect was observed in immunized animals and no adenovirus could be isolated from
      the urine or feces of vaccinated animals. Results showed that the recombinant
      virus was safe and could stimulate a long-lasting immune response in goats.
      CONCLUSIONS/SIGNIFICANCE: This strategy not only provides an effective PPR
      vaccine candidate for goats but may be a valuable mean by which to differentiate
      infected from vaccinated animals (the so-called DIVA approach).

PMID- 22623991
TI  - Response of sunflower (Helianthus annuus L.) leaf surface defenses to exogenous
      methyl jasmonate.
AB  - Helianthus annuus, the common sunflower, produces a complex array of secondary
      compounds that are secreted into glandular trichomes, specialized structures
      found on leaf surfaces and anther appendages of flowers. The primary components
      of these trichome secretions are sesquiterpene lactones (STL), a diverse class of
      compounds produced abundantly by the plant family Compositae and believed to
      contribute to plant defense against herbivory. We treated wild and cultivated H.
      annuus accessions with exogenous methyl jasmonate, a plant hormone that mediates
      plant defense against insect herbivores and certain classes of fungal pathogens.
      The wild sunflower produced a higher density of glandular trichomes on its leaves
      than the cultivar. Comparison of the profiles of glandular trichome extracts
      obtained by liquid chromatography-mass spectroscopy (LC-MS) showed that wild and
      cultivated H. annuus were qualitatively similar in surface chemistry, although
      differing in the relative size and proportion of various compounds detected.
      Despite observing consistent transcriptional responses to methyl jasmonate
      treatment, we detected no significant effect on glandular trichome density or LC
      MS profile in cultivated or wild sunflower, with wild sunflower exhibiting a
      declining trend in overall STL production and foliar glandular trichome density
      of jasmonate-treated plants. These results suggest that glandular trichomes and
      associated compounds may act as constitutive defenses or require greater levels
      of stimulus for induction than the observed transcriptional responses to
      exogenous jasmonate. Reduced defense investment in domesticated lines is
      consistent with predicted tradeoffs caused by selection for increased yield;
      future research will focus on the development of genetic resources to explicitly
      test the ecological roles of glandular trichomes and associated effects on plant
      growth and fitness.

PMID- 22623993
TI  - Efficacious intermittent dosing of a novel JAK2 inhibitor in mouse models of
      polycythemia vera.
AB  - A high percentage of patients with the myeloproliferative disorder polycythemia
      vera (PV) harbor a Val617->Phe activating mutation in the Janus kinase 2 (JAK2)
      gene, and both cell culture and mouse models have established a functional role
      for this mutation in the development of this disease. We describe the properties
      of MRLB-11055, a highly potent inhibitor of both the WT and V617F forms of JAK2,
      that has therapeutic efficacy in erythropoietin (EPO)-driven and JAK2V617F-driven
      mouse models of PV. In cultured cells, MRLB-11055 blocked proliferation and
      induced apoptosis in a manner consistent with JAK2 pathway inhibition. MRLB-11055
      effectively prevented EPO-induced STAT5 activation in the peripheral blood of
      acutely dosed mice, and could prevent EPO-induced splenomegaly and erythrocytosis
      in chronically dosed mice. In a bone marrow reconstituted JAK2V617F-luciferase
      murine PV model, MRLB-11055 rapidly reduced the burden of JAK2V617F-expressing
      cells from both the spleen and the bone marrow. Using real-time in vivo imaging,
      we examined the kinetics of disease regression and resurgence, enabling the
      development of an intermittent dosing schedule that achieved significant
      reductions in both erythroid and myeloid populations with minimal impact on
      lymphoid cells. Our studies provide a rationale for the use of non-continuous
      treatment to provide optimal therapy for PV patients.

PMID- 22623992
TI  - EGFR soluble isoforms and their transcripts are expressed in meningiomas.
AB  - The EGFR (epidermal growth factor receptor) is involved in the oncogenesis of
      many tumors. In addition to the full-length EGFR (isoform a), normal and tumor
      cells produce soluble EGFR isoforms (sEGFR) that lack the intracellular domain.
      sEGFR isoforms b, c and d are encoded by EGFR variants 2 (v2), 3 (v3) and 4 (v4)
      mRNA resulting from gene alternative splicing. Accordingly, the results of EGFR
      protein expression analysis depend on the domain targeted by the antibodies. In
      meningiomas, EGFR expression investigations mainly focused on EGFR isoform a.
      sEGFR and EGFRvIII mutant, that encodes a constitutively active truncated
      receptor, have not been studied. In a 69 meningiomas series, protein expression
      was analyzed by immunohistochemistry using extracellular domain targeted antibody
      (ECD-Ab) and intracellular domain targeted antibody (ICD-Ab). EGFRv1 to v4 and
      EGFRvIII mRNAs were quantified by RT-PCR and EGFR amplification revealed by MLPA.
      Results were analyzed with respect to clinical data, tumor resection (Simpson
      grade), histological type, tumor grade, and patient outcome.Immunochemical
      staining was stronger with ECD-Ab than with ICD-Ab. Meningiomas expressed EGFRv1
      to -v4 mRNAs but not EGFRvIII mutant. Intermediate or high ECD-Ab staining and
      high EGFRv1 to v4 mRNA levels were associated to a better progression free
      survival (PFS). PFS was also improved in women, when tumor resection was
      evaluated as Simpson 1 or 2, in grade I vs. grade II and III meningiomas and when
      Ki67 labeling index was lower than 10%. Our results suggest that, EGFR protein
      isoforms without ICD and their corresponding mRNA variants are expressed in
      meningiomas in addition to the whole isoform a. EGFRvIII was not expressed. High
      expression levels seem to be related to a better prognosis. These results
      indicate that the oncogenetic mechanisms involving the EGFR pathway in
      meningiomas could be different from other tumor types.

PMID- 22623994
TI  - Predictors of HIV and syphilis among men who have sex with men in a Chinese
      metropolitan city: comparison of risks among students and non-students.
AB  - BACKGROUND: Men who have sex with men (MSM) are at a substantial risk of HIV,
      given rising HIV prevalence in urban China. Adolescent and adult students often
      take HIV-related risk as part of sexual exploration. We compared the risks of HIV
      and syphilis infections and risky sexual behaviors between student and non
      student among urban MSM. METHODS: Respondent driven sampling approach was used to
      recruit men who were self-identified as MSM in Chongqing Metropolitan City in
      southwestern China in 2009. Each participant completed a computer-assisted self
      interview which collected demographic and behavioral data, and provided blood
      specimens for HIV and syphilis testing. Multivariable logistic regression
      analyses identified predictors for HIV and syphilis infections while comparing
      student and non-student MSM. RESULTS: Among 503 MSM participants, 36.4% were
      students, of whom 84.2% were in college. The adjusted prevalence of HIV infection
      was 5.5% (95% confidence interval [CI]: 2.1%-10.2%) in students and 20.9% (95%
      CI: 13.7%-27.5%) in non-students; the adjusted prevalence of syphilis was 4.4%
      (95% CI: 0.7%-9.0%) in students and 7.9% (95% CI: 3.6%-12.9%) in non-students (P
      = 0.12). Two groups had similar risky sexual behaviors such as number of sexual
      partners and exchanging sex for money. Multivariate analysis showed that students
      had lower HIV prevalence than non-students (adjusted odds ratio [AOR]: 0.3; 95%
      CI: 0.1-0.8) adjusting for age, ethnicity and other variables. CONCLUSION:
      Student MSM have lower HIV and similar syphilis prevalence compared with non
      student MSM. However, due to a shorter duration of sexual experience and high
      prevalence of at-risk sexual behaviors among student MSM, HIV risk might be quite
      high in students as in non-students.

PMID- 22623995
TI  - Panton-Valentine leukocidin is not the primary determinant of outcome for
      Staphylococcus aureus skin infections: evaluation from the CANVAS studies.
AB  - The impact of Panton-Valentine leukocidin (PVL) on the severity of complicated
      skin and skin structure infections (cSSSI) caused by Staphylococcus aureus is
      controversial. We evaluated potential associations between clinical outcome and
      PVL presence in both methicillin-resistant S. aureus (MRSA) and methicillin
      susceptible S. aureus (MSSA) isolates from patients enrolled in two large,
      multinational phase three clinical trials assessing ceftaroline fosamil for the
      treatment of cSSSI (the CANVAS 1 and 2 programs). Isolates from all
      microbiologically evaluable patients with monomicrobial MRSA or MSSA infections
      (n = 473) were genotyped by PCR for pvl and underwent pulsed-field gel
      electrophoresis (PFGE). Genes encoding pvl were present in 266/473 (56.2%)
      isolates. Infections caused by pvl-positive S. aureus were associated with
      younger patient age, North American acquisition, and presence of major abscesses
      (P<0.001 for each). Cure rates of patients infected with pvl-positive and pvl
      negative S. aureus were similar overall (93.6% versus 92.8%; P = 0.72), and
      within MRSA-infected (94.5% vs. 93.1%; P = 0.67) and MSSA-infected patients
      (92.2% vs. 92.7%; P = 1.00). This finding persisted after adjustment for multiple
      patient characteristics. Outcomes were also similar when USA300 PVL+ and non
      USA300 PVL+ infections were compared. The results of this contemporary,
      international study suggest that pvl presence was not the primary determinant of
      outcome in patients with cSSSI due to either MRSA or MSSA.

PMID- 22623996
TI  - alpha-Thalassemia impairs the cytoadherence of Plasmodium falciparum-infected
      erythrocytes.
AB  - BACKGROUND: alpha-Thalassemia results from decreased production of alpha-globin
      chains that make up part of hemoglobin tetramers (Hb; alpha(2)beta(2)) and
      affects up to 50% of individuals in some regions of sub-Saharan Africa.
      Heterozygous (-alpha/alphaalpha) and homozygous (-alpha/-alpha) genotypes are
      associated with reduced risk of severe Plasmodium falciparum malaria, but the
      mechanism of this protection remains obscure. We hypothesized that alpha
      thalassemia impairs the adherence of parasitized red blood cells (RBCs) to
      microvascular endothelial cells (MVECs) and monocytes--two interactions that are
      centrally involved in the pathogenesis of severe disease. METHODS AND FINDINGS:
      We obtained P. falciparum isolates directly from Malian children with malaria and
      used them to infect alphaalpha/alphaalpha (normal), -alpha/alphaalpha and -alpha/
      alpha RBCs. We also used laboratory-adapted P. falciparum clones to infect -/
      alpha RBCs obtained from patients with HbH disease. Following a single cycle of
      parasite invasion and maturation to the trophozoite stage, we tested the ability
      of parasitized RBCs to bind MVECs and monocytes. Compared to parasitized
      alphaalpha/alphaalpha RBCs, we found that parasitized -alpha/alphaalpha, -alpha/
      alpha and -/-alpha RBCs showed, respectively, 22%, 43% and 63% reductions in
      binding to MVECs and 13%, 33% and 63% reductions in binding to monocytes. alpha
      Thalassemia was associated with abnormal display of P. falciparum erythrocyte
      membrane protein 1 (PfEMP1), the parasite's main cytoadherence ligand and
      virulence factor, on the surface of parasitized RBCs. CONCLUSIONS: Parasitized
      alpha-thalassemic RBCs show PfEMP1 display abnormalities that are reminiscent of
      those on the surface of parasitized sickle HbS and HbC RBCs. Our data suggest a
      model of malaria protection in which alpha-thalassemia ameliorates the pro
      inflammatory effects of cytoadherence. Our findings also raise the possibility
      that other unstable hemoglobins such as HbE and unpaired alpha-globin chains (in
      the case of beta-thalassemia) protect against life-threatening malaria by a
      similar mechanism.

PMID- 22623997
TI  - Memory immune responses against pandemic (H1N1) 2009 influenza virus induced by a
      whole particle vaccine in cynomolgus monkeys carrying Mafa-A1*052:02.
AB  - We made an H1N1 vaccine candidate from a virus library consisting of 144 ( = 16
      HA*9 NA) non-pathogenic influenza A viruses and examined its protective effects
      against a pandemic (2009) H1N1 strain using immunologically naive cynomolgus
      macaques to exclude preexisting immunity and to employ a preclinical study since
      preexisting immunity in humans previously vaccinated or infected with influenza
      virus might make comparison of vaccine efficacy difficult. Furthermore, macaques
      carrying a major histocompatibility complex class I molecule, Mafa-A1*052:02,
      were used to analyze peptide-specific CD8(+) T cell responses. Sera of macaques
      immunized with an inactivated whole particle formulation without addition of an
      adjuvant showed higher neutralization titers against the vaccine strain
      A/Hokkaido/2/1981 (H1N1) than did sera of macaques immunized with a split
      formulation. Neutralization activities against the pandemic strain
      A/Narita/1/2009 (H1N1) in sera of macaques immunized twice with the split vaccine
      reached levels similar to those in sera of macaques immunized once with the whole
      particle vaccine. After inoculation with the pandemic virus, the virus was
      detected in nasal samples of unvaccinated macaques for 6 days after infection and
      for 2.67 days and 5.33 days on average in macaques vaccinated with the whole
      particle vaccine and the split vaccine, respectively. After the challenge
      infection, recall neutralizing antibody responses against the pandemic virus and
      CD8(+) T cell responses specific for nucleoprotein peptide NP262-270 bound to
      Mafa-A1*052:02 in macaques vaccinated with the whole particle vaccine were
      observed more promptly or more vigorously than those in macaques vaccinated with
      the split vaccine. These findings demonstrated that the vaccine derived from our
      virus library was effective for pandemic virus infection in macaques and that the
      whole particle vaccine conferred more effective memory and broader cross-reactive
      immune responses to macaques against pandemic influenza virus infection than did
      the split vaccine.

PMID- 22623998
TI  - The behavioural response of Australian fur seals to motor boat noise.
AB  - Australian fur seals breed on thirteen islands located in the Bass Strait,
      Australia. Land access to these islands is restricted, minimising human presence
      but boat access is still permissible with limitations on approach distances.
      Thirty-two controlled noise exposure experiments were conducted on breeding
      Australian fur seals to determine their behavioural response to controlled in-air
      motor boat noise on Kanowna Island (39 degrees 10'S, 146 degrees 18'E). Our
      results show there were significant differences in the seals' behaviour at low
      (64-70 dB) versus high (75-85 dB) sound levels, with seals orientating themselves
      towards or physically moving away from the louder boat noise at three different
      sound levels. Furthermore, seals responded more aggressively with one another and
      were more alert when they heard louder boat noise. Australian fur seals
      demonstrated plasticity in their vocal responses to boat noise with calls being
      significantly different between the various sound intensities and barks tending
      to get faster as the boat noise got louder. These results suggest that Australian
      fur seals on Kanowna Island show behavioural disturbance to high level boat
      noise. Consequently, it is recommended that an appropriate level of received boat
      sound emissions at breeding fur seal colonies be below 74 dB and that these
      findings be taken into account when evaluating appropriate approach distances and
      speed limits for boats.

PMID- 22623999
TI  - Matrix rigidity regulates cancer cell growth by modulating cellular metabolism
      and protein synthesis.
AB  - BACKGROUND: Tumor cells in vivo encounter diverse types of microenvironments both
      at the site of the primary tumor and at sites of distant metastases.
      Understanding how the various mechanical properties of these microenvironments
      affect the biology of tumor cells during disease progression is critical in
      identifying molecular targets for cancer therapy. METHODOLOGY/PRINCIPAL FINDINGS:
      This study uses flexible polyacrylamide gels as substrates for cell growth in
      conjunction with a novel proteomic approach to identify the properties of
      rigidity-dependent cancer cell lines that contribute to their differential growth
      on soft and rigid substrates. Compared to cells growing on more rigid/stiff
      substrates (>10,000 Pa), cells on soft substrates (150-300 Pa) exhibited a longer
      cell cycle, due predominantly to an extension of the G1 phase of the cell cycle,
      and were metabolically less active, showing decreased levels of intracellular ATP
      and a marked reduction in protein synthesis. Using stable isotope labeling of
      amino acids in culture (SILAC) and mass spectrometry, we measured the rates of
      protein synthesis of over 1200 cellular proteins under growth conditions on soft
      and rigid/stiff substrates. We identified cellular proteins whose syntheses were
      either preferentially inhibited or preserved on soft matrices. The former
      category included proteins that regulate cytoskeletal structures (e.g., tubulins)
      and glycolysis (e.g., phosphofructokinase-1), whereas the latter category
      included proteins that regulate key metabolic pathways required for survival,
      e.g., nicotinamide phosphoribosyltransferase, a regulator of the NAD salvage
      pathway. CONCLUSIONS/SIGNIFICANCE: The cellular properties of rigidity-dependent
      cancer cells growing on soft matrices are reminiscent of the properties of
      dormant cancer cells, e.g., slow growth rate and reduced metabolism. We suggest
      that the use of relatively soft gels as cell culture substrates would allow
      molecular pathways to be studied under conditions that reflect the different
      mechanical environments encountered by cancer cells upon metastasis to distant
      sites.

PMID- 22624000
TI  - Five year incidence of visual field loss in adult Chinese. The Beijing Eye Study.
AB  - PURPOSE: To describe the cumulative 5 year incidence of visual field loss in
      adult Chinese in Greater Beijing. METHODS: The Beijing Eye Study 2006 included
      3251 subjects (mean age 60.4+/-10.1 years) who had participated in the Beijing
      Eye Study 2001 and returned for re-examination. All participants underwent a
      comprehensive eye examination, including visual field test by frequency doubling
      threshold perimetry. An abnormal visual field was defined as reduced sensitivity
      in at least one test location. Incident visual field loss was defined as a change
      in visual field from normal at baseline to abnormal at follow-up. RESULTS: An
      incident visual field loss was detected in 273 eyes (4.3+/-0.5%)/235 subjects
      (7.3+/-0.5%). It was significantly associated with higher age (P = 0.001), higher
      intraocular pressure (P<0.001), and higher fasting blood glucose concentration (P
      = 0.019). Considering only eyes (n = 140) with a detected cause for visual field
      loss, the most frequent causes were cataract (68 (48.6%) eyes) followed by
      glaucoma (23 (16.4%) eyes), diabetic retinopathy (13 (9.3%) eyes), age-related
      macular degeneration (10 (7.1%) eyes), and myopic degenerative retinopathy (9
      (6.4%) eyes). For 133 (48.7%) eyes with a visual field loss, the cause for the
      VFL remained unclear. CONCLUSIONS: The 5-year incidence of visual field loss was
      4.3+/-0.5% per eye or 7.3+/-0.5% per subject. It increased significantly with
      age, intraocular pressure, and fasting blood glucose level. Major causes for the
      incidence of visual field loss were cataract, glaucoma and diabetic retinopathy.

PMID- 22624001
TI  - An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.
AB  - There is an urgent need for potent inhibitors of dengue virus (DENV) replication
      for the treatment and/or prophylaxis of infections with this virus. We here
      report on an aglycon analogue of the antibiotic teicoplanin (code name LCTA-949)
      that inhibits DENV-induced cytopathic effect (CPE) in a dose-dependent manner.
      Virus infection was completely inhibited at concentrations that had no adverse
      effect on the host cells. These findings were corroborated by quantification of
      viral RNA levels in culture supernatant. Antiviral activity was also observed
      against other flaviviruses such as the yellow fever virus and the tick-borne
      encephalitis virus (TBEV). In particular, potent antiviral activity was observed
      against TBEV. Time-of-drug-addition experiments indicated that LCTA-949 inhibits
      an early stage in the DENV replication cycle; however, a virucidal effect was
      excluded. This observation was corroborated by the fact that LCTA-949 lacks
      activity on DENV subgenomic replicon (that does not encode structural proteins)
      replication. Using a microsopy-based binding and fusion assay employing DiD
      labeled viruses, it was shown that LCTA-949 targets the early stage
      (binding/entry) of the infection. Moreover, LCTA-949 efficiently inhibits
      infectivity of DENV particles pre-opsonized with antibodies, thus potentially
      also inhibiting antibody-dependent enhancement (ADE). In conclusion, LCTA-949
      exerts in vitro activity against several flaviviruses and does so (as shown for
      DENV) by interfering with an early step in the viral replication cycle.

PMID- 22624002
TI  - Human hepatitis B virus production in avian cells is characterized by enhanced
      RNA splicing and the presence of capsids containing shortened genomes.
AB  - Experimental studies on hepatitis B virus (HBV) replication are commonly done
      with human hepatoma cells to reflect the natural species and tissue tropism of
      the virus. However, HBV can also replicate, upon transfection of virus coding
      plasmids, in cells of other species. In such cross-species transfection
      experiments with chicken LMH hepatoma cells, we previously observed the formation
      of HBV genomes with aberrant electrophoretic mobility, in addition to the those
      DNA species commonly seen in human HepG2 hepatoma cells. Here, we report that
      these aberrant DNA forms are mainly due to excessive splicing of HBV pregenomic
      RNA and the abundant synthesis of spliced DNA products, equivalent to those also
      made in human cells, yet at much lower level. Mutation of the common splice
      acceptor site abolished splicing and in turn enhanced production of DNA from full
      length pgRNA in transfected LMH cells. The absence of splicing made other DNA
      molecules visible, that were shortened due to the lack of sequences in the core
      protein coding region. Furthermore, there was nearly full-length DNA in the
      cytoplasm of LMH cells that was not protected in viral capsids. Remarkably, we
      have previously observed similar shortened genomes and non-protected viral DNA in
      human HepG2 cells, yet exclusively in the nucleus where uncoating and final
      release of viral genomes occurs. Hence, two effects reflecting capsid disassembly
      in the nucleus in human HepG2 cells are seen in the cytoplasm of chicken LMH
      cells.

PMID- 22624004
TI  - Diverse temperate bacteriophage carriage in Clostridium difficile 027 strains.
AB  - BACKGROUND: The hypervirulent Clostridium difficile ribotype 027 can be
      classified into subtypes, but it unknown if these differ in terms of severity of
      C. difficile infection (CDI). Genomic studies of C. difficile 027 strains have
      established that they are rich in mobile genetic elements including prophages.
      This study combined physiological studies, electron microscopy analysis and
      molecular biology to determine the potential role of temperate bacteriophages in
      disease and diversity of C. difficile 027. METHODOLOGY/PRINCIPAL FINDINGS: We
      induced prophages from 91 clinical C. difficile 027 isolates and used
      transmission electron microscopy and pulsed-field gel electrophoresis to
      characterise the bacteriophages present. We established a correlation between
      phage morphology and subtype. Morphologically distinct tailed bacteriophages
      belonging to Myoviridae and Siphoviridae were identified in 63 and three
      isolates, respectively. Dual phage carriage was observed in four isolates. In
      addition, there were inducible phage tail-like particles (PT-LPs) in all
      isolates. The capacity of two antibiotics mitomycin C and norfloxacin to induce
      prophages was compared and it was shown that they induced specific prophages from
      C. difficile isolates. A PCR assay targeting the capsid gene of the myoviruses
      was designed to examine molecular diversity of C. difficile myoviruses.
      Phylogenetic analysis of the capsid gene sequences from eight ribotypes showed
      that all sequences found in the ribotype 027 isolates were identical and distinct
      from other C. difficile ribotypes and other bacteria species.
      CONCLUSION/SIGNIFICANCE: A diverse set of temperate bacteriophages are associated
      with C. difficile 027. The observed correlation between phage carriage and the
      subtypes suggests that temperate bacteriophages contribute to the diversity of C.
      difficile 027 and may play a role in severity of disease associated with this
      ribotype. The capsid gene can be used as a tool to identify C. difficile
      myoviruses present within bacterial genomes.

PMID- 22624003
TI  - Polymyxin B inadequately quenches the effects of contaminating lipopolysaccharide
      on murine dendritic cells.
AB  - Dendritic cell (DC) activation is commonly used as a measure of the
      immunomodulatory potential of candidate exogenous and endogenous molecules.
      Residual lipopolysaccharide (LPS) contamination is a recurring theme and the
      potency of LPS is not always fully appreciated. To address this, polymyxin B
      (PmB) is often used to neutralise contaminating LPS. However, the limited
      capacity of this antibiotic to successfully block these effects is neglected.
      Therefore, this study aimed to determine the minimum LPS concentration required
      to induce murine bone marrow-derived dendritic cell (BMDC) maturation and
      cytokine secretion and to assess the ability of PmB to inhibit these processes.
      LPS concentrations as low as 10 pg/ml and 20 pg/ml induced secretion of
      interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha respectively, while a
      concentration of 50 pg/ml promoted secretion of IL-12p40. A much higher threshold
      exists for IL-12p70 as an LPS concentration of 500 pg/ml was required to induce
      secretion of this cytokine. The efficacy of PmB varied substantially for
      different cytokines but this antibiotic was particularly limited in its ability
      to inhibit LPS-induced secretion of IL-6 and TNF-alpha. Furthermore, an LPS
      concentration of 50 pg/ml was sufficient to promote DC expression of
      costimulatory molecules and PmB was limited in its capacity to reverse this
      process when LPS concentrations of greater than 20 ng/ml were used. There is a
      common perception that LPS is heat resistant. However, heat treatment attenuated
      the ability of low concentrations of LPS to induce secretion of IL-6 and IL-12p40
      by BMDCs, thus suggesting that heat-inactivation of protein preparations is also
      an ineffective control for discounting potential LPS contamination. Finally, LPS
      concentrations of less than 10 pg/ml were incapable of promoting secretion of IL
      6 independently but could synergise with heat-labile enterotoxin (LT) to promote
      IL-6, indicating that reducing contaminating endotoxin concentrations to low
      pg/ml concentrations is essential to avoid misleading conclusions regarding
      candidate immunomodulators.

PMID- 22624005
TI  - Genetic and mechanistic evaluation for the mixed-field agglutination in B3 blood
      type with IVS3+5G>A ABO gene mutation.
AB  - BACKGROUND: The ABO blood type B(3) is the most common B subtype in the Chinese
      population with a frequency of 1/900. Although IVS3+5G>A (rs55852701) mutation of
      B gene has been shown to associate with the development of B(3) blood type,
      genetic and mechanistic evaluation for the unique mixed-field agglutination
      phenotype has not yet been completely addressed. METHODOLOGY/PRINCIPAL FINDINGS:
      In this study, we analyzed 16 cases of confirmed B(3) individuals and found that
      IVS3+5G>A attributes to all cases of B(3). RT-PCR analyses revealed the presence
      of at least 7 types of aberrant B(3) splicing transcripts with most of the
      transcripts causing early termination and producing non-functional protein during
      translation. The splicing transcript without exon 3 that was predicted to
      generate functional B(3) glycosyltransferase lacking 19 amino acids at the N
      terminal segment constituted only 0.9% of the splicing transcripts. Expression of
      the B(3) cDNA with exon 3 deletion in the K562 erythroleukemia cells revealed
      that the B(3) glycosyltransferase had only 40% of B(1) activity in converting H
      antigen to B antigen. Notably, the typical mixed-field agglutination of B(3)-RBCs
      can be mimicked by adding anti-B antibody to the K562-B(3) cells.
      CONCLUSIONS/SIGNIFICANCE: This study thereby demonstrates that both aberrant
      splicing of B transcripts and the reduced B(3) glycosyltransferase activity
      contribute to weak B expression and the mixed-field agglutination of B(3), adding
      to the complexity for the regulatory mechanisms of ABO gene expression.

PMID- 22624006
TI  - Joint effects of febrile acute infection and an interferon-gamma polymorphism on
      breast cancer risk.
AB  - BACKGROUND: There is an inverse relationship between febrile infection and the
      risk of malignancies. Interferon gamma (IFN-gamma) plays an important role in
      fever induction and its expression increases with incubation at fever-range
      temperatures. Therefore, the genetic polymorphism of IFN-gamma may modify the
      association of febrile infection with breast cancer risk. METHODOLOGY AND
      PRINCIPAL FINDINGS: Information on potential breast cancer risk factors, history
      of fever during the last 10 years, and blood specimens were collected from 839
      incident breast cancer cases and 863 age-matched controls between October 2008
      and June 2010 in Guangzhou, China. IFN-gamma (rs2069705) was genotyped using a
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      platform. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated
      using multivariate logistic regression. We found that women who had experienced
      >=1 fever per year had a decreased risk of breast cancer [ORs and 95% CI: 0.77
      (0.61-0.99)] compared to those with less than one fever a year. This association
      only occurred in women with CT/TT genotypes [0.54 (0.37-0.77)] but not in those
      with the CC genotype [1.09 (0.77-1.55)]. The association of IFN-gamma rs2069705
      with the risk of breast cancer was not significant among all participants, while
      the CT/TT genotypes were significantly related to an elevated risk of breast
      cancer [1.32 (1.03-1.70)] among the women with <1 fever per year and to a reduced
      risk of breast cancer [0.63 (0.40-0.99)] among women with >=1 fever per year
      compared to the CC genotype. A marked interaction between fever frequencies and
      the IFN-gamma genotypes was observed (P for multiplicative and additive
      interactions were 0.005 and 0.058, respectively). CONCLUSIONS: Our findings
      indicate a possible link between febrile acute infection and a decreased risk of
      breast cancer, and this association was modified by IFN-gamma rs2069705.

PMID- 22624007
TI  - When art moves the eyes: a behavioral and eye-tracking study.
AB  - The aim of this study was to investigate, using eye-tracking technique, the
      influence of bottom-up and top-down processes on visual behavior while subjects,
      naive to art criticism, were presented with representational paintings. Forty-two
      subjects viewed color and black and white paintings (Color) categorized as
      dynamic or static (Dynamism) (bottom-up processes). Half of the images
      represented natural environments and half human subjects (Content); all stimuli
      were displayed under aesthetic and movement judgment conditions (Task) (top-down
      processes). Results on gazing behavior showed that content-related top-down
      processes prevailed over low-level visually-driven bottom-up processes when a
      human subject is represented in the painting. On the contrary, bottom-up
      processes, mediated by low-level visual features, particularly affected gazing
      behavior when looking at nature-content images. We discuss our results proposing
      a reconsideration of the definition of content-related top-down processes in
      accordance with the concept of embodied simulation in art perception.

PMID- 22624008
TI  - Graph theoretical model of a sensorimotor connectome in zebrafish.
AB  - Mapping the detailed connectivity patterns (connectomes) of neural circuits is a
      central goal of neuroscience. The best quantitative approach to analyzing
      connectome data is still unclear but graph theory has been used with success. We
      present a graph theoretical model of the posterior lateral line sensorimotor
      pathway in zebrafish. The model includes 2,616 neurons and 167,114 synaptic
      connections. Model neurons represent known cell types in zebrafish larvae, and
      connections were set stochastically following rules based on biological
      literature. Thus, our model is a uniquely detailed computational representation
      of a vertebrate connectome. The connectome has low overall connection density,
      with 2.45% of all possible connections, a value within the physiological range.
      We used graph theoretical tools to compare the zebrafish connectome graph to
      small-world, random and structured random graphs of the same size. For each type
      of graph, 100 randomly generated instantiations were considered. Degree
      distribution (the number of connections per neuron) varied more in the zebrafish
      graph than in same size graphs with less biological detail. There was high local
      clustering and a short average path length between nodes, implying a small-world
      structure similar to other neural connectomes and complex networks. The graph was
      found not to be scale-free, in agreement with some other neural connectomes. An
      experimental lesion was performed that targeted three model brain neurons,
      including the Mauthner neuron, known to control fast escape turns. The lesion
      decreased the number of short paths between sensory and motor neurons analogous
      to the behavioral effects of the same lesion in zebrafish. This model is
      expandable and can be used to organize and interpret a growing database of
      information on the zebrafish connectome.

PMID- 22624009
TI  - Responses to dehydration in the one-humped camel and effects of blocking the
      renin-angiotensin system.
AB  - Our objectives were to compare the levels of circulating electrolytes, hormones,
      and renal function during 20 days of dehydration in camels versus the level in
      non-dehydrated camels and to record the effect of blocking angiotensin II AT1
      receptors with losartan during dehydration. Dehydration induced significant
      increments in serum sodium, creatinine, urea, a substantial fall in body weight,
      and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone,
      however, was unaltered compared with time-matched controls. Losartan
      significantly enhanced the effect of dehydration to reduce body weight and
      increase serum levels of creatinine and urea, whilst also impairing the rise in
      plasma AVP and reducing aldosterone levels. We conclude that dehydration in the
      camel induces substantial increments in serum sodium, creatinine, urea and AVP
      levels; that aldosterone levels are altered little by dehydration; that blockade
      of angiotensin II type 1 receptors enhances the dehydration-induced fall in body
      weight and increase in serum creatinine and urea levels whilst reducing
      aldosterone and attenuating the rise in plasma AVP.

PMID- 22624010
TI  - Kinship shapes affiliative social networks but not aggression in ring-tailed
      coatis.
AB  - Animal groups typically contain individuals with varying degrees of genetic
      relatedness, and this variation in kinship has a major influence on patterns of
      aggression and affiliative behaviors. This link between kinship and social
      behavior underlies socioecological models which have been developed to explain
      how and why different types of animal societies evolve. We tested if kinship and
      age-sex class homophily in two groups of ring-tailed coatis (Nasua nasua)
      predicted the network structure of three different social behaviors: 1)
      association, 2) grooming, and 3) aggression. Each group was studied during two
      consecutive years, resulting in four group-years available for analysis (total of
      65 individuals). Association patterns were heavily influenced by agonistic
      interactions which typically occurred during feeding competition. Grooming
      networks were shaped by mother-offspring bonds, female-female social
      relationships, and a strong social attraction to adult males. Mother-offspring
      pairs were more likely to associate and groom each other, but relatedness had no
      effect on patterns of aggressive behavior. Additionally, kinship had little to no
      effect on coalitionary support during agonistic interactions. Adult females
      commonly came to the aid of juveniles during fights with other group members, but
      females often supported juveniles who were not their offspring (57% of
      coalitionary interactions). These patterns did not conform to predictions from
      socioecological models.

PMID- 22624011
TI  - The neural basis of decision-making and reward processing in adults with euthymic
      bipolar disorder or attention-deficit/hyperactivity disorder (ADHD).
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder
      (BD) share DSM-IV criteria in adults and cause problems in decision-making.
      Nevertheless, no previous report has assessed a decision-making task that
      includes the examination of the neural correlates of reward and gambling in
      adults with ADHD and those with BD. METHODOLOGY/PRINCIPAL FINDINGS: We used the
      Iowa gambling task (IGT), a task of rational decision-making under risk (RDMUR)
      and a rapid-decision gambling task (RDGT) which elicits behavioral measures as
      well as event-related potentials (ERPs: fERN and P3) in connection to the
      motivational impact of events. We did not observe between-group differences for
      decision-making under risk or ambiguity (RDMUR and IGT); however, there were
      significant differences for the ERP-assessed RDGT. Compared to controls, the ADHD
      group showed a pattern of impaired learning by feedback (fERN) and insensitivity
      to reward magnitude (P3). This ERP pattern (fERN and P3) was associated with
      impulsivity, hyperactivity, executive function and working memory. Compared to
      controls, the BD group showed fERN- and P3-enhanced responses to reward magnitude
      regardless of valence. This ERP pattern (fERN and P3) was associated with mood
      and inhibitory control. Consistent with the ERP findings, an analysis of source
      location revealed reduced responses of the cingulate cortex to the valence and
      magnitude of rewards in patients with ADHD and BD. CONCLUSIONS/SIGNIFICANCE: Our
      data suggest that neurophysiological (ERPs) paradigms such as the RDGT are well
      suited to assess subclinical decision-making processes in patients with ADHD and
      BD as well as for linking the cingulate cortex with action monitoring systems.

PMID- 22624012
TI  - Expression of an epitope-tagged virulence protein in Rickettsia parkeri using
      transposon insertion.
AB  - Despite recent advances in our ability to genetically manipulate Rickettsia,
      little has been done to employ genetic tools to study the expression and
      localization of Rickettsia virulence proteins. Using a mariner-based Himar1
      transposition system, we expressed an epitope-tagged variant of the actin
      polymerizing protein RickA under the control of its native promoter in Rickettsia
      parkeri, allowing the detection of RickA using commercially-available antibodies.
      Native RickA and epitope-tagged RickA exhibited similar levels of expression and
      were specifically localized to bacteria. To further facilitate protein expression
      in Rickettsia, we also developed a plasmid for Rickettsia insertion and
      expression (pRIE), containing a variant Himar1 transposon with enhanced
      flexibility for gene insertion, and used it to generate R. parkeri strains
      expressing diverse fluorescent proteins. Expression of epitope-tagged proteins in
      Rickettsia will expand our ability to assess the regulation and function of
      important virulence factors.

PMID- 22624013
TI  - Homeostatic regulation of Salmonella-induced mucosal inflammation and injury by
      IL-23.
AB  - IL-12 and IL-23 regulate innate and adaptive immunity to microbial pathogens
      through influencing the expression of IFN-gamma, IL-17, and IL-22. Herein we
      define the roles of IL-12 and IL-23 in regulating host resistance and intestinal
      inflammation during acute Salmonella infection. We find that IL-23 alone is
      dispensable for protection against systemic spread of bacteria, but synergizes
      with IL-12 for optimal protection. IL-12 promotes the production of IFN-gamma by
      NK cells, which is required for resistance against Salmonella and also for
      induction of intestinal inflammation and epithelial injury. In contrast, IL-23
      controls the severity of inflammation by inhibiting IL-12A expression, reducing
      IFN-gamma and preventing excessive mucosal injury. Our studies demonstrate that
      IL-23 is a homeostatic regulator of IL-12-dependent, IFN-gamma-mediated
      intestinal inflammation.

PMID- 22624014
TI  - Tumor blood flow differs between mouse strains: consequences for vasoresponse to
      photodynamic therapy.
AB  - Fluctuations in tumor blood flow are common and attributed to factors such as
      vasomotion or local vascular structure, yet, because vessel structure and
      physiology are host-derived, animal strain of tumor propagation may further
      determine blood flow characteristics. In the present report, baseline and stress
      altered tumor hemodynamics as a function of murine strain were studied using
      radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in
      tumor blood flow during one hour of baseline monitoring or during vascular stress
      induced by photodynamic therapy (PDT) were measured by diffuse correlation
      spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly
      correlated with heart rate and with similar median periods (i.e., ~9 and 14 min
      in C3H and nudes, respectively). However, tumor blood flow in C3H animals was
      more sensitive to physiologic or stress-induced perturbations. Specifically, PDT
      induced vascular insults produced greater decreases in blood flow in the tumors
      of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in
      blood flow were more regular and more prevalent within the tumors of C3H mice
      versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in
      C3H mice but did not affect tumor blood flow in nudes. Underlying differences in
      vascular structure, such as smaller tumor blood vessels in C3H versus nude
      animals, may contribute to strain-dependent variation in vascular function. These
      data thus identify clear effects of mouse strain on tumor hemodynamics with
      consequences to PDT and potentially other vascular-mediated therapies.

PMID- 22624015
TI  - Plant food delphinidin-3-glucoside significantly inhibits platelet activation and
      thrombosis: novel protective roles against cardiovascular diseases.
AB  - Delphinidin-3-glucoside (Dp-3-g) is one of the predominant bioactive compounds of
      anthocyanins in many plant foods. Although several anthocyanin compounds have
      been reported to be protective against cardiovascular diseases (CVDs), the direct
      effect of anthocyanins on platelets, the key players in atherothrombosis, has not
      been studied. The roles of Dp-3-g in platelet function are completely unknown.
      The present study investigated the effects of Dp-3-g on platelet activation and
      several thrombosis models in vitro and in vivo. We found that Dp-3-g
      significantly inhibited human and murine platelet aggregation in both platelet
      rich plasma and purified platelets. It also markedly reduced thrombus growth in
      human and murine blood in perfusion chambers at both low and high shear rates.
      Using intravital microscopy, we observed that Dp-3-g decreased platelet
      deposition, destabilized thrombi, and prolonged the time required for vessel
      occlusion. Dp-3-g also significantly inhibited thrombus growth in a carotid
      artery thrombosis model. To elucidate the mechanisms, we examined platelet
      activation markers via flow cytometry and found that Dp-3-g significantly
      inhibited the expression of P-selectin, CD63, CD40L, which reflect platelet alpha
      and delta-granule release, and cytosol protein secretion, respectively. We
      further demonstrated that Dp-3-g downregulated the expression of active integrin
      alphaIIbbeta3 on platelets, and attenuated fibrinogen binding to platelets
      following agonist treatment, without interfering with the direct interaction
      between fibrinogen and integrin alphaIIbbeta3. We found that Dp-3-g reduced
      phosphorylation of adenosine monophosphate-activated protein kinase, which may
      contribute to the observed inhibitory effects on platelet activation. Thus, Dp-3
      g significantly inhibits platelet activation and attenuates thrombus growth at
      both arterial and venous shear stresses, which likely contributes to its
      protective roles against thrombosis and CVDs.

PMID- 22624017
TI  - Differences in walking pattern during 6-min walk test between patients with COPD
      and healthy subjects.
AB  - BACKGROUND: To date, detailed analyses of walking patterns using accelerometers
      during the 6-min walk test (6MWT) have not been performed in patients with
      chronic obstructive pulmonary disease (COPD). Therefore, it remains unclear
      whether and to what extent COPD patients have an altered walking pattern during
      the 6MWT compared to healthy elderly subjects. METHODOLOGY/PRINCIPAL FINDINGS: 79
      COPD patients and 24 healthy elderly subjects performed the 6MWT wearing an
      accelerometer attached to the trunk. The accelerometer features (walking
      intensity, cadence, and walking variability) and subject characteristics were
      assessed and compared between groups. Moreover, associations were sought with 6
      min walk distance (6MWD) using multiple ordinary least squares (OLS) regression
      models. COPD patients walked with a significantly lower walking intensity, lower
      cadence and increased walking variability compared to healthy subjects. Walking
      intensity and height were the only two significant determinants of 6MWD in
      healthy subjects, explaining 85% of the variance in 6MWD. In COPD patients also
      age, cadence, walking variability measures and their interactions were included
      were significant determinants of 6MWD (total variance in 6MWD explained: 88%).
      CONCLUSIONS/SIGNIFICANCE: COPD patients have an altered walking pattern during
      6MWT compared to healthy subjects. These differences in walking pattern partially
      explain the lower 6MWD in patients with COPD.

PMID- 22624016
TI  - Persistent gastric colonization with Burkholderia pseudomallei and dissemination
      from the gastrointestinal tract following mucosal inoculation of mice.
AB  - Melioidosis is a disease of humans caused by opportunistic infection with the
      soil and water bacterium Burkholderia pseudomallei. Melioidosis can manifest as
      an acute, overwhelming infection or as a chronic, recurrent infection. At
      present, it is not clear where B. pseudomallei resides in the mammalian host
      during the chronic, recurrent phase of infection. To address this question, we
      developed a mouse low-dose mucosal challenge model of chronic B. pseudomallei
      infection and investigated sites of bacterial persistence over 60 days. Sensitive
      culture techniques and selective media were used to quantitate bacterial burden
      in major organs, including the gastrointestinal (GI) tract. We found that the GI
      tract was the primary site of bacterial persistence during the chronic infection
      phase, and was the only site from which the organism could be consistently
      cultured during a 60-day infection period. The organism could be repeatedly
      recovered from all levels of the GI tract, and chronic infection was accompanied
      by sustained low-level fecal shedding. The stomach was identified as the primary
      site of GI colonization as determined by fluorescent in situ hybridization.
      Organisms in the stomach were associated with the gastric mucosal surface, and
      the propensity to colonize the gastric mucosa was observed with 4 different B.
      pseudomallei isolates. In contrast, B. pseudomallei organisms were present at low
      numbers within luminal contents in the small and large intestine and cecum
      relative to the stomach. Notably, inflammatory lesions were not detected in any
      GI tissue examined in chronically-infected mice. Only low-dose oral or intranasal
      inoculation led to GI colonization and development of chronic infection of the
      spleen and liver. Thus, we concluded that in a mouse model of melioidosis B.
      pseudomallei preferentially colonizes the stomach following oral inoculation, and
      that the chronically colonized GI tract likely serves as a reservoir for
      dissemination of infection to extra-intestinal sites.

PMID- 22624018
TI  - Comparing aerodynamic efficiency in birds and bats suggests better flight
      performance in birds.
AB  - Flight is one of the energetically most costly activities in the animal kingdom,
      suggesting that natural selection should work to optimize flight performance. The
      similar size and flight speed of birds and bats may therefore suggest convergent
      aerodynamic performance; alternatively, flight performance could be restricted by
      phylogenetic constraints. We test which of these scenarios fit to two measures of
      aerodynamic flight efficiency in two passerine bird species and two New World
      leaf-nosed bat species. Using time-resolved particle image velocimetry
      measurements of the wake of the animals flying in a wind tunnel, we derived the
      span efficiency, a metric for the efficiency of generating lift, and the lift-to
      drag ratio, a metric for mechanical energetic flight efficiency. We show that the
      birds significantly outperform the bats in both metrics, which we ascribe to
      variation in aerodynamic function of body and wing upstroke: Bird bodies
      generated relatively more lift than bat bodies, resulting in a more uniform
      spanwise lift distribution and higher span efficiency. A likely explanation would
      be that the bat ears and nose leaf, associated with echolocation, disturb the
      flow over the body. During the upstroke, the birds retract their wings to make
      them aerodynamically inactive, while the membranous bat wings generate thrust and
      negative lift. Despite the differences in performance, the wake morphology of
      both birds and bats resemble the optimal wake for their respective lift-to-drag
      ratio regimes. This suggests that evolution has optimized performance relative to
      the respective conditions of birds and bats, but that maximum performance is
      possibly limited by phylogenetic constraints. Although ecological differences
      between birds and bats are subjected to many conspiring variables, the different
      aerodynamic flight efficiency for the bird and bat species studied here may help
      explain why birds typically fly faster, migrate more frequently and migrate
      longer distances than bats.

PMID- 22624019
TI  - The association between cesarean delivery on maternal request and method of
      newborn feeding in China.
AB  - BACKGROUND: Cesarean delivery has increased significantly during the last
      decades. This study aimed to investigate the association between planned mode of
      delivery and method of feeding. METHODOLOGY/PRINCIPAL FINDINGS: A cohort was
      created retrospectively using data from a population-based maternal and child
      health surveillance system, which covers 27 study sites in China from 1993 to
      2006. The cohort consisted of 431,704 women for analysis, including 22,462 women
      with planned cesarean delivery on maternal request (CDMR) and 409,242 women with
      planned vaginal delivery (VD). Logistic regression models were used to examine
      the association between mode of delivery and method of feeding adjusting for
      selected covariates. In this cohort, 398,176 (92.2%) women exclusively breastfed
      their baby, 28,798 (6.7%) women chose mixed feeding, and 4,730 (1.1%) women chose
      formula feeding before hospital discharge. Women who planned CDMR were less
      likely to exclusively breastfeed and more likely to formula feed their babies
      than those who planned VD. After adjusting for covariates, the odds ratios were
      0.85 (95% CI: 0.81-0.89) for exclusive breastfeeding and 1.61 (95% CI: 1.45-1.79)
      for formula feeding. Associations between planned mode of delivery and method of
      feeding in the south, north, rural and urban areas yielded similar results.
      CONCLUSION: This study demonstrated that planned CDMR was associated with a lower
      rate of exclusive breastfeeding and a higher rate of formula feeding in a low
      risk Chinese population.

PMID- 22624020
TI  - Denaturing gradient gel electrophoresis (DGGE) as a powerful novel alternative
      for differentiation of epizootic ISA virus variants.
AB  - Infectious Salmon Anemia is a devastating disease critically affecting world-wide
      salmon production. Chile has been particularly stricken by this disease which in
      all cases has been directly related with its causative agent, a novel
      orthomyxovirus which presents specific and distinctive infective features. Among
      these, two molecular markers have been directly associated with pathogenicity in
      two of the eight RNA sub genomic coding units of the virus: an insertion hot spot
      region present in viral segment 5 and a Highly Polymorphic Region (HPR) located
      in viral segment 6. Here we report the successful adaptation of a PCR-dependent
      denaturing gel electrophoresis technique (DGGE), which enables differentiation of
      selected reported HPR epizootic variants detected in Chile. At the same time, the
      technique allows us to distinguish one nucleotide differences in sequences
      associated with the intriguing, and still not well-understood, insertion events
      which tend to occur on RNA Segment 5. Thus, the versatility of the technique
      opens new opportunities for improved understanding of the complex biology of all
      ISA variants as well as possible applications to other highly variable pathogens.

PMID- 22624021
TI  - Increased mobility of metal oxide nanoparticles due to photo and thermal induced
      disagglomeration.
AB  - Significant advances have been made on our understanding of the fate and
      transport of engineered nanomaterials. One unexplored aspect of nanoparticle
      aggregation is how environmental stimuli such as light exposure and temperature
      variations affect the mobility of engineered nanoparticles. In this study,
      TiO(2), ZnO, and CeO(2) were chosen as model materials for investigating the
      mobility of nanoparticles under three external stimuli: heat, light and
      sonication. Sunlight and high power sonication were able to partially
      disagglomerate metal oxide clusters, but primary particles bonded by solid state
      necks were left intact. A cycle of temperature increase from 25 degrees C to 65
      degrees C and then decrease back was found to disagglomerate the compact clusters
      in the heating phase and reagglomerate them as more open fractal structures
      during the cooling phase. A fractal model summing the pair-wise DLVO interactions
      between primary particles within two fractal agglomerates predicts weak
      attractions on the order of a few kT. Our study shows that common environmental
      stimuli such as light exposure or temperature variation can disagglomerate
      nanoparticle clusters and enhance their mobility in open waters. This phenomenon
      warrants attention since it is likely that metal oxide nanoparticles will
      experience these natural stimuli during their transport in the environment.

PMID- 22624022
TI  - Stenotrophomonas maltophilia infections in a general hospital: patient
      characteristics, antimicrobial susceptibility, and treatment outcome.
AB  - INTRODUCTION: Stenotrophomonas maltophilia is acquiring increasing importance as
      a nosocomial pathogen. METHODS: We retrospectively studied the characteristics
      and outcome of patients with any type of S. maltophilia infection at the
      University Hospital of Heraklion, Crete, Greece, between 1/2005-12/2010. S.
      maltophilia antimicrobial susceptibility was tested with the agar dilution
      method. Prognostic factors for all-cause in-hospital mortality were assessed with
      multivariate logistic regression. RESULTS: Sixty-eight patients (median age: 70.5
      years; 64.7% males) with S. maltophilia infection, not related to cystic
      fibrosis, were included. The 68 patients were hospitalized in medical (29.4%),
      surgical (26.5%), hematology/oncology departments (23.5%), or the intensive care
      units (ICU; 20.6%). The most frequent infection types were respiratory tract
      (54.4%), bloodstream (16.2%), skin/soft tissue (10.3%), and intra-abdominal
      (8.8%) infection. The S. maltophilia-associated infection was polymicrobial in
      33.8% of the cases. In vitro susceptibility was higher to colistin (91.2%),
      trimethoprim/sulfamethoxazole and netilmicin (85.3% each), and ciprofloxacin
      (82.4%). The empirical and the targeted treatment regimens were microbiologically
      appropriate for 47.3% and 63.6% of the 55 patients with data available,
      respectively. Most patients received targeted therapy with a combination of
      agents other than trimethoprim/sulfamethoxazole. The crude mortality and the
      mortality and the S. maltophilia infection-related mortality were 14.7% and 4.4%,
      respectively. ICU hospitalization was the only independent prognostic factor for
      mortality. CONCLUSION: S. maltophilia infection in a general hospital can be
      associated with a good prognosis, except for the patients hospitalized in the
      ICU. Combination reigmens with fluoroquinolones, colistin, or tigecycline could
      be alternative treatment options to trimethoprim/sulfamethoxazole.

PMID- 22624023
TI  - Activity patterns during food provisioning are affected by artificial light in
      free living great tits (Parus major).
AB  - Artificial light may have severe ecological consequences but there is limited
      experimental work to assess these consequences. We carried out an experimental
      study on a wild population of great tits (Parus major) to assess the impact of
      light pollution on daily activity patterns during the chick provisioning period.
      Pairs that were provided with a small light outside their nest box did not alter
      the onset, cessation or duration of their working day. There was however a clear
      effect of artificial light on the feeding rate in the second half of the nestling
      period: when provided with artificial light females increased their feeding rate
      when the nestlings were between 9 and 16 days old. Artificial light is
      hypothesised to have affected the perceived photoperiod of either the parents or
      the offspring which in turn led to increased parental care. This may have
      negative fitness consequences for the parents, and light pollution may thus
      create an ecological trap for breeding birds.

PMID- 22624024
TI  - A low concentration of ethanol impairs learning but not motor and sensory
      behavior in Drosophila larvae.
AB  - Drosophila melanogaster has proven to be a useful model system for the genetic
      analysis of ethanol-associated behaviors. However, past studies have focused on
      the response of the adult fly to large, and often sedating, doses of ethanol. The
      pharmacological effects of low and moderate quantities of ethanol have remained
      understudied. In this study, we tested the acute effects of low doses of ethanol
      (~7 mM internal concentration) on Drosophila larvae. While ethanol did not affect
      locomotion or the response to an odorant, we observed that ethanol impaired
      associative olfactory learning when the heat shock unconditioned stimulus (US)
      intensity was low but not when the heat shock US intensity was high. We
      determined that the reduction in learning at low US intensity was not a result of
      ethanol anesthesia since ethanol-treated larvae responded to the heat shock in
      the same manner as untreated animals. Instead, low doses of ethanol likely impair
      the neuronal plasticity that underlies olfactory associative learning. This
      impairment in learning was reversible indicating that exposure to low doses of
      ethanol does not leave any long lasting behavioral or physiological effects.

PMID- 22624026
TI  - Images of eyes enhance investments in a real-life public good.
AB  - A key issue in cooperation research is to determine the conditions under which
      individuals invest in a public good. Here, we tested whether cues of being
      watched increase investments in an anonymous public good situation in real life.
      We examined whether individuals would invest more by removing experimentally
      placed garbage (paper and plastic bottles) from bus stop benches in Geneva in the
      presence of images of eyes compared to controls (images of flowers). We provided
      separate bins for each of both types of garbage to investigate whether
      individuals would deposit more items into the appropriate bin in the presence of
      eyes. The treatment had no effect on the likelihood that individuals present at
      the bus stop would remove garbage. However, those individuals that engaged in
      garbage clearing, and were thus likely affected by the treatment, invested more
      time to do so in the presence of eyes. Images of eyes had a direct effect on
      behaviour, rather than merely enhancing attention towards a symbolic sign
      requesting removal of garbage. These findings show that simple images of eyes can
      trigger reputational effects that significantly enhance on non-monetary
      investments in anonymous public goods under real life conditions. We discuss our
      results in the light of previous findings and suggest that human social behaviour
      may often be shaped by relatively simple and potentially unconscious mechanisms
      instead of very complex cognitive capacities.

PMID- 22624025
TI  - A panel of serum microRNAs as specific biomarkers for diagnosis of compound- and
      herb-induced liver injury in rats.
AB  - BACKGROUND: Drug-induced liver injury (DILI) has been a public, economic and
      pharmaceutical issue for many years. Enormous effort has been made for
      discovering and developing novel biomarkers for diagnosing and monitoring both
      clinical and preclinical DILI at an early stage, though progress has been
      relatively slow. Additionally, herb-induced liver injury is an emerging cause of
      liver disease because herbal medicines are increasingly being used worldwide.
      Recently, circulating microRNAs (miRNAs) have shown potential to serve as novel,
      minimally invasive biomarkers to diagnose and monitor human cancers and other
      diseases at early stages. METHODOLOGY/PRINCIPAL FINDINGS: In order to identify
      candidate miRNAs as diagnostic biomarkers for DILI, miRNA expression profiles of
      serum and liver tissue from two parallel liver injury Sprague-Dawley rat models
      induced by a compound (acetaminophen, APAP) or an herb (Dioscorea bulbifera, DB)
      were screened in this study. The initial screens were performed on serum using a
      MicroRNA TaqMan low-density qPCR array and on liver tissue using a miRCURY LNA
      hybridization array and were followed by a TaqMan probe-based quantitative
      reverse transcription-PCR (qRT-PCR) assay to validate comparison with serum
      biochemical parameters and histopathological examination. Two sets of
      dysregulated miRNA candidates in serum and liver tissue were selected in the
      screening phase. After qRT-PCR validation, a panel of compound- and herb- related
      serum miRNAs was identified. CONCLUSIONS/SIGNIFICANCE: We have demonstrated that
      this panel of serum miRNAs provides potential biomarkers for diagnosis of DILI
      with high sensitivity and specificity.

PMID- 22624027
TI  - Cervical, anal and oral HPV in an adolescent inner-city health clinic providing
      free vaccinations.
AB  - OBJECTIVES: Published human papillomavirus (HPV) vaccine trials indicate efficacy
      is strongest for those naive to the vaccine-types. However, few high-risk young
      women have been followed and cervical HPV has been the predominant outcome
      measure. METHODS: We collected cervical and anal swabs, as well as oral rinse
      specimens from 645 sexually active inner-city young females attending a large
      adolescent health-clinic in New York City that offers free care and HPV
      vaccination. Specimens were tested for HPV-DNA using a MY09/MY11-PCR system. Type
      specific prevalence of HPV at each anatomic site was compared for individuals by
      vaccination dose using generalized estimating equation logistic regression
      models. RESULTS: The majority of subjects reported being of non-Caucasian (92%)
      and/or Hispanic ethnicity (61%). Median age was 18 years (range:14-20). All had
      practiced vaginal sex, a third (33%) practiced anal sex, and most (77%) had also
      engaged in oral sex. At enrollment, 21% had not received the vaccine and 51% had
      received three doses. Prevalent HPV infection at enrollment was detected in 54%
      of cervical, 42% of anal and 20% of oral specimens, with vaccine types present in
      7%, 6% and 1% of specimens, respectively. Comparing prevalence for vaccine types,
      the detection of HPV in the cervix of vaccinated compared to unvaccinated
      adolescents was significantly reduced: HPV6/11 (odds ratio [OR] = 0.19,
      95%CI:0.06-0.75), HPV16 (OR = 0.31, 95%CI:0.11-0.88) and HPV18 (OR = 0.14,
      95%CI:0.03-0.75). For anal HPV, the risk of detecting vaccine types HPV6/11 (OR =
      0.27, 95%CI:0.10-0.72) and HPV18(OR = 0.12, 95%CI:0.01-1.16) were significantly
      reduced for vaccinated adolescents however, the risk for HPV16 was not
      significantly decreased (OR = 0.63, 95%CI:0.18-2.20). CONCLUSION: HPV Prevalence
      is extremely high in inner-city female adolescents. Administration of the HPV
      vaccine reduced the risk for cervical HPV; however continued follow-up is
      required to assess the protection for HPV at all sites in young women with high
      exposure.

PMID- 22624028
TI  - Automated solid-phase subcloning based on beads brought into proximity by
      magnetic force.
AB  - In the fields of proteomics, metabolic engineering and synthetic biology there is
      a need for high-throughput and reliable cloning methods to facilitate
      construction of expression vectors and genetic pathways. Here, we describe a new
      approach for solid-phase cloning in which both the vector and the gene are
      immobilized to separate paramagnetic beads and brought into proximity by magnetic
      force. Ligation events were directly evaluated using fluorescent-based microscopy
      and flow cytometry. The highest ligation efficiencies were obtained when gene-
      and vector-coated beads were brought into close contact by application of a
      magnet during the ligation step. An automated procedure was developed using a
      laboratory workstation to transfer genes into various expression vectors and more
      than 95% correct clones were obtained in a number of various applications. The
      method presented here is suitable for efficient subcloning in an automated manner
      to rapidly generate a large number of gene constructs in various vectors intended
      for high throughput applications.

PMID- 22624029
TI  - Cks1 is required for tumor cell proliferation but not sufficient to induce
      hematopoietic malignancies.
AB  - The Cks1 component of the SCF(Skp2) complex is necessary for p27(Kip1)
      ubiquitylation and degradation. Cks1 expression is elevated in various B cell
      malignancies including Burkitt lymphoma and multiple myeloma. We have previously
      shown that loss of Cks1 results in elevated p27(Kip1) levels and delayed tumor
      development in a mouse model of Myc-induced B cell lymphoma. Surprisingly, loss
      of Skp2 in the same mouse model also resulted in elevated p27(Kip1) levels but
      exhibited no impact on tumor onset. This raises the possibility that Cks1 could
      have other oncogenic activities than suppressing p27(Kip1). To challenge this
      notion we have targeted overexpression of Cks1 to B cells using a conditional
      retroviral bone marrow transduction-transplantation system. Despite potent
      ectopic overexpression, Cks1 was unable to promote B cell hyperproliferation or B
      cell malignancies, indicating that Cks1 is not oncogenic when overexpressed in B
      cells. Since Skp2 overexpression can drive T-cell tumorigenesis or other cancers
      we also widened the quest for oncogenic activity of Cks1 by ubiquitously
      expressing Cks1 in hematopoetic progenitors. At variance with c-Myc
      overexpression, which caused acute myeloid leukemia, Cks1 overexpression did not
      induce myeloproliferation or leukemia. Therefore, despite being associated with a
      poor prognosis in various malignancies, sole Cks1 expression is insufficient to
      induce lymphoma or a myeloproliferative disease in vivo.

PMID- 22624031
TI  - Uncovering dangerous cheats: how do avian hosts recognize adult brood parasites?
AB  - BACKGROUND: Co-evolutionary struggles between dangerous enemies (e.g., brood
      parasites) and their victims (hosts) lead to the emergence of sophisticated
      adaptations and counter-adaptations. Salient host tricks to reduce parasitism
      costs include, as front line defence, adult enemy discrimination. In contrast to
      the well studied egg stage, investigations addressing the specific cues for adult
      enemy recognition are rare. Previous studies have suggested barred underparts and
      yellow eyes may provide cues for the recognition of cuckoos Cuculus canorus by
      their hosts; however, no study to date has examined the role of the two cues
      simultaneously under a consistent experimental paradigm. METHODOLOGY/PRINCIPAL
      FINDINGS: We modify and extend previous work using a novel experimental approach-
      custom-made dummies with various combinations of hypothesized recognition cues.
      The salient recognition cue turned out to be the yellow eye. Barred underparts,
      the only trait examined previously, had a statistically significant but small
      effect on host aggression highlighting the importance of effect size vs.
      statistical significance. CONCLUSION: Relative importance of eye vs. underpart
      phenotypes may reflect ecological context of host-parasite interaction: yellow
      eyes are conspicuous from the typical direction of host arrival (from above),
      whereas barred underparts are poorly visible (being visually blocked by the upper
      part of the cuckoo's body). This visual constraint may reduce usefulness of
      barred underparts as a reliable recognition cue under a typical situation near
      host nests. We propose a novel hypothesis that recognition cues for enemy
      detection can vary in a context-dependent manner (e.g., depending on whether the
      enemy is approached from below or from above). Further we suggest a particular
      cue can trigger fear reactions (escape) in some hosts/populations whereas the
      same cue can trigger aggression (attack) in other hosts/populations depending on
      presence/absence of dangerous enemies that are phenotypically similar to brood
      parasites and costs and benefits associated with particular host responses.

PMID- 22624030
TI  - Targeting aquaporin function: potent inhibition of aquaglyceroporin-3 by a gold
      based compound.
AB  - Aquaporins (AQPs) are membrane channels that conduct water and small solutes such
      as glycerol and are involved in many physiological functions. Aquaporin-based
      modulator drugs are predicted to be of broad potential utility in the treatment
      of several diseases. Until today few AQP inhibitors have been described as
      suitable candidates for clinical development. Here we report on the potent
      inhibition of AQP3 channels by gold(III) complexes screened on human red blood
      cells (hRBC) and AQP3-transfected PC12 cells by a stopped-flow method. Among the
      various metal compounds tested, Auphen is the most active on AQP3 (IC(50) = 0.8+/
      0.08 uM in hRBC). Interestingly, the compound poorly affects the water
      permeability of AQP1. The mechanism of gold inhibition is related to the ability
      of Au(III) to interact with sulphydryls groups of proteins such as the thiolates
      of cysteine residues. Additional DFT and modeling studies on possible gold
      compound/AQP adducts provide a tentative description of the system at a molecular
      level. The mapping of the periplasmic surface of an homology model of human AQP3
      evidenced the thiol group of Cys40 as a likely candidate for binding to gold(III)
      complexes. Moreover, the investigation of non-covalent binding of Au complexes by
      docking approaches revealed their preferential binding to AQP3 with respect to
      AQP1. The high selectivity and low concentration dependent inhibitory effect of
      Auphen (in the nanomolar range) together with its high water solubility makes the
      compound a suitable drug lead for future in vivo studies. These results may
      present novel metal-based scaffolds for AQP drug development.

PMID- 22624032
TI  - PARP-1 Val762Ala polymorphism is associated with risk of cervical carcinoma.
AB  - PARP-1 is a nuclear enzyme that plays an important role in DNA repair,
      recombination, proliferation and the genome stability. The PARP-1 Val762Ala
      polymorphism has been associated with increased risk of developing cancers of the
      prostate, esophagus and lung. The aim of this study was to determine whether the
      PARP-1 Val762Ala polymorphism is associated with the risk of cervical carcinoma.
      MA-PCR was used to genotype the PARP-1 Val762Ala polymorphism in 539 women with
      cervical carcinoma, 480 women with CIN and 800 controls. The genotyping method
      was confirmed by the DNA sequencing analysis. The PARP-1 Val762Ala polymorphism
      was not associated with the risk of CIN. However, women carrying the PARP-1
      Ala762Ala genotype were significantly susceptible to cervical carcinoma (OR:
      2.70, 95% CI: 1.47-3.70), and the similar results were also found in squamous
      cell carcinoma (OR: 2.56, 95% CI: 1.47-3.70). In HPV positive population, the
      PARP-1 Ala762Ala genotype was also associated with increased risk of cervical
      carcinoma (OR: 5.56, 95% CI: 2.08-14.3). Our results indicate that the PARP-1
      Ala762Ala genotype increases the risk of cervical carcinoma.

PMID- 22624034
TI  - Intricate correlation between body posture, personality trait and incidence of
      body pain: a cross-referential study report.
AB  - OBJECTIVE: Occupational back pain is a disorder that commonly affects the working
      population, resulting in disability, health-care utilization, and a heavy
      socioeconomic burden. Although the etiology of occupational pain remains largely
      unsolved, anecdotal evidence exists for the contribution of personality and
      posture to long-term pain management, pointing to a direct contribution of the
      mind-body axis. In the current study, we have conducted an extensive evaluation
      into the relationships between posture and personality. METHOD: We have sampled a
      random population of 100 subjects (50 men and 50 women) in the age range of 13-82
      years based on their personality and biomechanical profiles. All subjects were
      French-Canadian, living in Canada between the Quebec and Sorel-Tracy areas. The
      Biotonix analyses and report were used on the subjects being tested in order to
      distinguish postural deviations. Personality was determined by using the Myers
      Briggs Type Indicator questionnaire. RESULTS: We establish a correlation between
      ideal and kyphosis-lordosis postures and extraverted personalities. Conversely,
      our studies establish a correlative relationship between flat back and sway-back
      postures with introverted personalities. CONCLUSION: Overall, our studies
      establish a novel correlative relationship between personality, posture and pain.

PMID- 22624033
TI  - Spatial reorientation by geometry in bumblebees.
AB  - Human and non-human animals are capable of using basic geometric information to
      reorient in an environment. Geometric information includes metric properties
      associated with spatial surfaces (e.g., short vs. long wall) and left-right
      directionality or 'sense' (e.g. a long wall to the left of a short wall).
      However, it remains unclear whether geometric information is encoded by
      explicitly computing the layout of surface geometry or by matching images of the
      environment. View-based spatial encoding is generally thought to hold for insect
      navigation and, very recently, evidence for navigation by geometry has been
      reported in ants but only in a condition which does not allow the animals to use
      features located far from the goal. In this study we tested the spatial
      reorientation abilities of bumblebees (Bombus terrestris). After spatial
      disorientation, by passive rotation both clockwise and anticlockwise, bumblebees
      had to find one of the four exit holes located in the corners of a rectangular
      enclosure. Bumblebees systematically confused geometrically equivalent exit
      corners (i.e. corners with the same geometric arrangement of metric properties
      and sense, for example a short wall to the left of a long wall). However, when
      one wall of the enclosure was a different colour, bumblebees appeared to combine
      this featural information (either near or far from the goal) with geometric
      information to find the correct exit corner. Our results show that bumblebees are
      able to use both geometric and featural information to reorient themselves, even
      when features are located far from the goal.

PMID- 22624035
TI  - Exosome-related multi-pass transmembrane protein TSAP6 is a target of rhomboid
      protease RHBDD1-induced proteolysis.
AB  - We have previously reported that rhomboid domain containing 1 (RHBDD1), a
      mammalian rhomboid protease highly expressed in the testis, can cleave the Bcl-2
      protein Bik. In this study, we identified a multi-pass transmembrane protein,
      tumor suppressor activated pathway-6 (TSAP6) as a potential substrate of RHBDD1.
      RHBDD1 was found to induce the proteolysis of TSAP6 in a dose- and activity
      dependent manner. The cleavage of TSAP6 was not restricted to its glycosylated
      form and occurred in three different regions. In addition, mass spectrometry and
      mutagenesis analyses both indicated that the major cleavage site laid in the C
      terminal of the third transmembrane domain of TSAP6. A somatic cell knock-in
      approach was used to genetically inactivate the endogenous RHBDD1 in HCT116 and
      RKO colon cancer cells. Exosome secretion was significantly elevated when RHBDD1
      was inactivated in the two cells lines. The increased exosome secretion was
      verfied through the detection of certain exosomal components, including Tsg101,
      Tf-R, FasL and Trail. In addition, the elevation of exosome secretion by RHBDD1
      inactivation was reduced when TSAP6 was knocked down, indicating that the role of
      RHBDD1 in regulating exosomal trafficking is very likely to be TSAP6-dependent.
      We found that the increase in FasL and Trail increased exosome-induced apoptosis
      in Jurkat cells. Taken together, our findings suggest that RHBDD1 is involved in
      the regulation of a nonclassical exosomal secretion pathway through the
      restriction of TSAP6.

PMID- 22624036
TI  - Exposure to radiofrequency electromagnetic fields and sleep quality: a
      prospective cohort study.
AB  - BACKGROUND: There is persistent public concern about sleep disturbances due to
      radiofrequency electromagnetic field (RF-EMF) exposure. The aim of this
      prospective cohort study was to investigate whether sleep quality is affected by
      mobile phone use or by other RF-EMF sources in the everyday environment. METHODS:
      We conducted a prospective cohort study with 955 study participants aged between
      30 and 60 years. Sleep quality and daytime sleepiness was assessed by means of
      standardized questionnaires in May 2008 (baseline) and May 2009 (follow-up). We
      also asked about mobile and cordless phone use and asked study participants for
      consent to obtain their mobile phone connection data from the mobile phone
      operators. Exposure to environmental RF-EMF was computed for each study
      participant using a previously developed and validated prediction model. In a
      nested sample of 119 study participants, RF-EMF exposure was measured in the
      bedroom and data on sleep behavior was collected by means of actigraphy during
      two weeks. Data were analyzed using multivariable regression models adjusted for
      relevant confounders. RESULTS: In the longitudinal analyses neither operator
      recorded nor self-reported mobile phone use was associated with sleep
      disturbances or daytime sleepiness. Also, exposure to environmental RF-EMF did
      not affect self-reported sleep quality. The results from the longitudinal
      analyses were confirmed in the nested sleep study with objectively recorded
      exposure and measured sleep behavior data. CONCLUSIONS: We did not find evidence
      for adverse effects on sleep quality from RF-EMF exposure in our everyday
      environment.

PMID- 22624037
TI  - Dietary pseudopurpurin improves bone geometry architecture and metabolism in red
      bone Guishan goats.
AB  - Red-colored bones were found initially in some Guishan goats in the 1980s, and
      they were designated red-boned goats. However, it is not understood what causes
      the red color in the bone, or whether the red material changes the bone geometry,
      architecture, and metabolism of red-boned goats. Pseudopurpurin was identified in
      the red-colored material of the bone in red-boned goats by high-performance
      liquid chromatography-electrospray ionization-mass spetrometry and nuclear
      magnetic resonance analysis. Pseudopurpurin is one of the main constituents of
      Rubia cordifolia L, which is eaten by the goats. The assessment of the mechanical
      properties and micro-computed tomography showed that the red-boned goats
      displayed an increase in the trabecular volume fraction, trabecular thickness,
      and the number of trabeculae in the distal femur. The mean thickness, inner
      perimeter, outer perimeter, and area of the femoral diaphysis were also
      increased. In addition, the trabecular separation and structure model index of
      the distal femur were decreased, but the bone mineral density of the whole femur
      and the mechanical properties of the femoral diaphysis were enhanced in the red
      boned goats. Meanwhile, expression of alkaline phosphatase and osteocalcin mRNA
      was higher, and the ratio of the receptor activator of the nuclear factor kappa B
      ligand to osteoprotegerin was markedly lower in the bone marrow of the red-boned
      goats compared with common goats. To confirm further the effect of pseudopurpurin
      on bone geometry, architecture, and metabolism, Wistar rats were fed diets to
      which pseudopurpurin was added for 5 months. Similar changes were observed in the
      femurs of the treated rats. The above results demonstrate that pseudopurpurin has
      a close affinity with the mineral salts of bone, and consequently a high level of
      mineral salts in the bone cause an improvement in bone strength and an
      enhancement in the structure and metabolic functions of the bone.

PMID- 22624039
TI  - Analysis of C3 suggests three periods of positive selection events and different
      evolutionary patterns between fish and mammals.
AB  - BACKGROUND: The third complement component (C3) is a central protein of the
      complement system conserved from fish to mammals. It also showed distinct
      characteristics in different animal groups. Striking features of the fish
      complement system were unveiled, including prominent levels of extrahepatic
      expression and isotypic diversity of the complement components. The evidences of
      the involvement of complement system in the enhancement of B and T cell responses
      found in mammals indicated that the complement system also serves as a bridge
      between the innate and adaptive responses. For the reasons mentioned above, it is
      interesting to explore the evolutionary process of C3 genes and to investigate
      whether the huge differences between aquatic and terrestrial environments
      affected the C3 evolution between fish and mammals. METHODOLOGY/PRINCIPAL
      FINDINGS: Analysis revealed that these two groups of animals had experienced
      different evolution patterns. The mammalian C3 genes were under purifying
      selection pressure while the positive selection pressure was detected in fish C3
      genes. Three periods of positive selection events of C3 genes were also detected.
      Two happened on the ancestral lineages to all vertebrates and mammals,
      respectively, one happened on early period of fish evolutionary history.
      CONCLUSIONS/SIGNIFICANCE: Three periods of positive selection events had happened
      on C3 genes during history and the fish and mammals C3 genes experience different
      evolutionary patterns for their distinct living environments.

PMID- 22624038
TI  - Persistent systemic inflammation is associated with poor clinical outcomes in
      COPD: a novel phenotype.
AB  - BACKGROUND: Because chronic obstructive pulmonary disease (COPD) is a
      heterogeneous condition, the identification of specific clinical phenotypes is
      key to developing more effective therapies. To explore if the persistence of
      systemic inflammation is associated with poor clinical outcomes in COPD we
      assessed patients recruited to the well-characterized ECLIPSE cohort
      (NCT00292552). METHODS AND FINDINGS: Six inflammatory biomarkers in peripheral
      blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF
      alpha levels) were quantified in 1,755 COPD patients, 297 smokers with normal
      spirometry and 202 non-smoker controls that were followed-up for three years. We
      found that, at baseline, 30% of COPD patients did not show evidence of systemic
      inflammation whereas 16% had persistent systemic inflammation. Even though
      pulmonary abnormalities were similar in these two groups, persistently inflamed
      patients during follow-up had significantly increased all-cause mortality (13%
      vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs. 0.9 (1.1) per year,
      p<0.001) compared to non-inflamed ones. As a descriptive study our results show
      associations but do not prove causality. Besides this, the inflammatory response
      is complex and we studied only a limited panel of biomarkers, albeit they are
      those investigated by the majority of previous studies and are often and easily
      measured in clinical practice. CONCLUSIONS: Overall, these results identify a
      novel systemic inflammatory COPD phenotype that may be the target of specific
      research and treatment.

PMID- 22624040
TI  - A computational profiling of changes in gene expression and transcription factors
      induced by vFLIP K13 in primary effusion lymphoma.
AB  - Infection with Kaposi's sarcoma associated herpesvirus (KSHV) has been linked to
      the development of primary effusion lymphoma (PEL), a rare lymphoproliferative
      disorder that is characterized by loss of expression of most B cell markers and
      effusions in the body cavities. This unique clinical presentation of PEL has been
      attributed to their distinctive plasmablastic gene expression profile that shows
      overexpression of genes involved in inflammation, adhesion and invasion. KSHV
      encoded latent protein vFLIP K13 has been previously shown to promote the
      survival and proliferation of PEL cells. In this study, we employed gene array
      analysis to characterize the effect of K13 on global gene expression in PEL
      derived BCBL1 cells, which express negligible K13 endogenously. We demonstrate
      that K13 upregulates the expression of a number of NF-kappaB responsive genes
      involved in cytokine signaling, cell death, adhesion, inflammation and immune
      response, including two NF-kappaB subunits involved in the alternate NF-kappaB
      pathway, RELB and NFKB2. In contrast, CD19, a B cell marker, was one of the genes
      downregulated by K13. A comparison with K13-induced genes in human vascular
      endothelial cells revealed that although there was a considerable overlap among
      the genes induced by K13 in the two cell types, chemokines genes were
      preferentially induced in HUVEC with few exceptions, such as RANTES/CCL5, which
      was induced in both cell types. Functional studies confirmed that K13 activated
      the RANTES/CCL5 promoter through the NF-kappaB pathway. Taken collectively, our
      results suggest that K13 may contribute to the unique gene expression profile,
      immunophenotype and clinical presentation that are characteristics of KSHV
      associated PEL.

PMID- 22624041
TI  - Quantitative analysis and comparison study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2
      and [68Ga]Ga-NOTA-PRGD2 using a reference tissue model.
AB  - With favorable pharmacokinetics and binding affinity for alpha(v)beta(3)
      integrin, (18)F-labeled dimeric cyclic RGD peptide ([(18)F]FPPRGD2) has been
      intensively used as a PET imaging probe for lesion detection and therapy response
      monitoring. A recently introduced kit formulation method, which uses an (18)F
      fluoride-aluminum complex labeled RGD tracer ([(18)F]AlF-NOTA-PRGD2), provides a
      strategy for simplifying the labeling procedure to facilitate clinical
      translation. Meanwhile, an easy-to-prepare (68)Ga-labeled NOTA-PRGD2 has also
      been reported to have promising properties for imaging integrin alpha(v)beta(3).
      The purpose of this study is to quantitatively compare the pharmacokinetic
      parameters of [(18)F]FPPRGD2, [(18)F]AlF-NOTA-PRGD2, and [(68)Ga]Ga-NOTA-PRGD2.
      U87MG tumor-bearing mice underwent 60-min dynamic PET scans following the
      injection of three tracers. Kinetic parameters were calculated using Logan
      graphical analysis with reference tissue. Parametric maps were generated using
      voxel-level modeling. All three compounds showed high binding potential (Bp(ND) =
      k(3)/k(4)) in tumor voxels. [(18)F]AlF-NOTA-PRGD2 showed comparable Bp(ND) value
      (3.75+/-0.65) with those of [(18)F]FPPRGD2 (3.39+/-0.84) and [(68)Ga]Ga-NOTA
      PRGD2 (3.09+/-0.21) (p>0.05). Little difference was found in volume of
      distribution (V(T)) among these three RGD tracers in tumor, liver and muscle.
      Parametric maps showed similar kinetic parameters for all three tracers. We also
      demonstrated that the impact of non-specific binding could be eliminated in the
      kinetic analysis. Consequently, kinetic parameter estimation showed more
      comparable results among groups than static image analysis. In conclusion,
      [(18)F]AlF-NOTA-PRGD2 and [(68)Ga]Ga-NOTA-PRGD2 have comparable pharmacokinetics
      and quantitative parameters compared to those of [(18)F]FPPRGD2. Despite the
      apparent difference in tumor uptake (%ID/g determined from static images) and
      clearance pattern, the actual specific binding component extrapolated from
      kinetic modeling appears to be comparable for all three dimeric RGD tracers.

PMID- 22624042
TI  - Are you approaching me? Motor execution influences perceived action orientation.
AB  - Human observers are especially sensitive to the actions of conspecifics that
      match their own actions. This has been proposed to be critical for social
      interaction, providing the basis for empathy and joint action. However, the
      precise relation between observed and executed actions is still poorly
      understood. Do ongoing actions change the way observers perceive others' actions?
      To pursue this question, we exploited the bistability of depth-ambiguous point
      light walkers, which can be perceived as facing towards the viewer or as facing
      away from the viewer. We demonstrate that point-light walkers are perceived more
      often as facing the viewer when the observer is walking on a treadmill compared
      to when the observer is performing an action that does not match the observed
      behavior (e.g., cycling). These findings suggest that motor processes influence
      the perceived orientation of observed actions: Acting observers tend to perceive
      similar actions by conspecifics as oriented towards themselves. We discuss these
      results in light of the possible mechanisms subtending action-induced modulation
      of perception.

PMID- 22624043
TI  - Evolution of a novel muscle design in sea urchins (Echinodermata: Echinoidea).
AB  - The sea urchin (Echinodermata: Echinoidea) masticatory apparatus, or Aristotle's
      lantern, is a complex structure composed of numerous hard and soft components.
      The lantern is powered by various paired and unpaired muscle groups. We describe
      how one set of these muscles, the lantern protractor muscles, has evolved a
      specialized morphology. This morphology is characterized by the formation of
      adaxially-facing lobes perpendicular to the main orientation of the muscle,
      giving the protractor a frilled aspect in horizontal section. Histological and
      ultrastructural analyses show that the microstructure of frilled muscles is
      largely identical to that of conventional, flat muscles. Measurements of muscle
      dimensions in equally-sized specimens demonstrate that the frilled muscle design,
      in comparison to that of the flat muscle type, considerably increases muscle
      volume as well as the muscle's surface directed towards the interradial cavity, a
      compartment of the peripharyngeal coelom. Scanning electron microscopical
      observations reveal that the insertions of frilled and flat protractor muscles
      result in characteristic muscle scars on the stereom, reflecting the shapes of
      individual muscles. Our comparative study of 49 derived "regular" echinoid
      species using magnetic resonance imaging (MRI) shows that frilled protractor
      muscles are found only in taxa belonging to the families Toxopneustidae,
      Echinometridae, and Strongylocentrotidae. The onset of lobe formation during
      ontogenesis varies between species of these three families. Because frilled
      protractor muscles are best observed in situ, the application of a non-invasive
      imaging technique was crucial for the unequivocal identification of this
      morphological character on a large scale. Although it is currently possible only
      to speculate on the functional advantages which the frilled muscle morphology
      might confer, our study forms the anatomical and evolutionary framework for
      future analyses of this unusual muscle design among sea urchins.

PMID- 22624044
TI  - Essential role of the coxsackie- and adenovirus receptor (CAR) in development of
      the lymphatic system in mice.
AB  - The coxsackie- and adenovirus receptor (CAR) is a cell adhesion molecule
      predominantly associated with epithelial tight junctions in adult tissues. CAR is
      also expressed in cardiomyocytes and essential for heart development up to
      embryonic day 11.5, but not thereafter. CAR is not expressed in vascular
      endothelial cells but was recently detected in neonatal lymphatic vessels,
      suggesting that CAR could play a role in the development of the lymphatic system.
      To address this, we generated mice carrying a conditional deletion of the CAR
      gene (Cxadr) and knocked out CAR in the mouse embryo at different time points
      during post-cardiac development. Deletion of Cxadr from E12.5, but not from
      E13.5, resulted in subcutaneous edema, hemorrhage and embryonic death.
      Subcutaneous lymphatic vessels were dilated and structurally abnormal with gaps
      and holes present at lymphatic endothelial cell-cell junctions. Furthermore,
      lymphatic vessels were filled with erythrocytes showing a defect in the
      separation between the blood and lymphatic systems. Regionally, erythrocytes
      leaked out into the interstitium from leaky lymphatic vessels explaining the
      hemorrhage detected in CAR-deficient mouse embryos. The results show that CAR
      plays an essential role in development of the lymphatic vasculature in the mouse
      embryo by promoting appropriate formation of lymphatic endothelial cell-cell
      junctions.

PMID- 22624045
TI  - Structural dynamics of HIV-1 envelope Gp120 outer domain with V3 loop.
AB  - BACKGROUND: The net charge of the hypervariable V3 loop on the HIV-1 envelope
      gp120 outer domain plays a key role in modulating viral phenotype. However, the
      molecular mechanisms underlying the modulation remain poorly understood.
      METHODOLOGY/PRINCIPAL FINDINGS: By combining computational and experimental
      approaches, we examined how V3 net charge could influence the phenotype of the
      gp120 interaction surface. Molecular dynamics simulations of the identical gp120
      outer domain, carrying a V3 loop with net charge of +3 or +7, showed that the V3
      change alone could induce global changes in fluctuation and conformation of the
      loops involved in binding to CD4, coreceptor and antibodies. A neutralization
      study using the V3 recombinant HIV-1 infectious clones showed that the virus
      carrying the gp120 with +3 V3, but not with +7 V3, was resistant to
      neutralization by anti-CD4 binding site monoclonal antibodies. An information
      entropy study shows that otherwise variable surface of the gp120 outer domain,
      such as V3 and a region around the CD4 binding loop, are less heterogeneous in
      the gp120 subpopulation with +3 V3. CONCLUSIONS/SIGNIFICANCE: These results
      suggest that the HIV-1 gp120 V3 loop acts as an electrostatic modulator that
      influences the global structure and diversity of the interaction surface of the
      gp120 outer domain. Our findings will provide a novel structural basis to
      understand how HIV-1 adjusts relative replication fitness by V3 mutations.

PMID- 22624046
TI  - The dynamics of sensorimotor cortical oscillations during the observation of hand
      movements: an EEG study.
AB  - BACKGROUND: The observation of action done by others determines a
      desynchronization of the rhythms recorded from cortical central regions. Here, we
      examined whether the observation of different types of hand movements (target
      directed, non-target directed, cyclic and non-cyclic) elicits different EEG
      cortical temporal patterns. METHODOLOGY: Video-clips of four types of hand
      movements were shown to right-handed healthy participants. Two were target
      directed (grasping and pointing) motor acts; two were non-target directed
      (supinating and clenching) movements. Grasping and supinating were performed
      once, while pointing and clenching twice (cyclic movements). High-density EEG was
      recorded and analyzed by means of wavelet transform, subdividing the time course
      in time bins of 200 ms. The observation of all presented movements produced a
      desynchronization of alpha and beta rhythms in central and parietal regions. The
      rhythms desynchronized as soon as the hand movement started, the nadir being
      reached around 700 ms after movement onset. At the end of the movement, a large
      power rebound occurred for all bands. Target and non-target directed movements
      produced an alpha band desynchronization in the central electrodes at the same
      time, but with a stronger desynchronization and a prolonged rebound for target
      directed motor acts. Most interestingly, there was a clear correlation between
      the velocity profile of the observed movements and beta band modulation.
      SIGNIFICANCE: Our data show that the observation of motor acts determines a
      modulation of cortical rhythm analogous to that occurring during motor act
      execution. In particular, the cortical motor system closely follows the velocity
      of the observed movements. This finding provides strong evidence for the presence
      in humans of a mechanism (mirror mechanism) mapping action observation on action
      execution motor programs.

PMID- 22624047
TI  - IL-15 participates in the respiratory innate immune response to influenza virus
      infection.
AB  - Following influenza infection, natural killer (NK) cells function as interim
      effectors by suppressing viral replication until CD8 T cells are activated,
      proliferate, and are mobilized within the respiratory tract. Thus, NK cells are
      an important first line of defense against influenza virus. Here, in a murine
      model of influenza, we show that virally-induced IL-15 facilitates the
      trafficking of NK cells into the lung airways. Blocking IL-15 delays NK cell
      entry to the site of infection and results in a disregulated control of early
      viral replication. By the same principle, viral control by NK cells can be
      therapeutically enhanced via intranasal administration of exogenous IL-15 in the
      early days post influenza infection. In addition to controlling early viral
      replication, this IL-15-induced mobilization of NK cells to the lung airways has
      important downstream consequences on adaptive responses. Primarily, depletion of
      responding NK1.1+ NK cells is associated with reduced immigration of influenza
      specific CD8 T cells to the site of infection. Together this work suggests that
      local deposits of IL-15 in the lung airways regulate the coordinated innate and
      adaptive immune responses to influenza infection and may represent an important
      point of immune intervention.

PMID- 22624048
TI  - Atomic force mechanobiology of pluripotent stem cell-derived cardiomyocytes.
AB  - We describe a method using atomic force microscopy (AFM) to quantify the
      mechanobiological properties of pluripotent, stem cell-derived cardiomyocytes,
      including contraction force, rate, duration, and cellular elasticity. We measured
      beats from cardiomyocytes derived from induced pluripotent stem cells of healthy
      subjects and those with dilated cardiomyopathy, and from embryonic stem cell
      lines. We found that our AFM method could quantitate beat forces of single cells
      and clusters of cardiomyocytes. We demonstrate the dose-responsive, inotropic
      effect of norepinephrine and beta-adrenergic blockade of metoprolol.
      Cardiomyocytes derived from subjects with dilated cardiomyopathy showed decreased
      force and decreased cellular elasticity compared to controls. This AFM-based
      method can serve as a screening tool for the development of cardiac-active
      pharmacological agents, or as a platform for studying cardiomyocyte biology.

PMID- 22624050
TI  - Transgenic mice for a tamoxifen-induced, conditional expression of the Cre
      recombinase in osteoclasts.
AB  - BACKGROUND: Studies on osteoclasts, the bone resorbing cells, have remained
      limited due to the lack of transgenic mice allowing the conditional knockout of
      genes in osteoclasts at any time during development or adulthood.
      METHODOLOGY/PRINCIPAL FINDING: We report here on the generation of transgenic
      mice which specifically express a tamoxifen-inducible Cre recombinase in
      osteoclasts. These mice, generated on C57BL/6 and FVB background, express a
      fusion Cre recombinase-ERT2 protein whose expression is driven by the promoter of
      cathepsin K (CtsK), a gene highly expressed in osteoclasts. We tested the
      cellular specificity of Cre activity in CtsKCreERT2 strains by breeding with
      Rosa26LacZ reporter mice. PCR and histological analyses of the CtsKCreERT2LacZ
      positive adult mice and E17.5 embryos show that Cre activity is restricted
      largely to bone tissue. In vitro, primary osteoclasts derived from the bone
      marrow of CtsKCreERT2+/-LacZ+/- adult mice show a Cre-dependent beta
      galactosidase activity after tamoxifen stimulation. CONCLUSIONS/SIGNIFICANCE: We
      have generated transgenic lines that enable the tamoxifen-induced, conditional
      deletion of loxP-flanked genes in osteoclasts, thus circumventing embryonic and
      postnatal gene lethality and avoiding gene deletion in other cell types. Such
      CtsKCreERT2 mice provide a convenient tool to study in vivo the different facets
      of osteoclast function in bone physiology during different developmental stages
      and adulthood of mice.

PMID- 22624049
TI  - AMP affects intracellular Ca2+ signaling, migration, cytokine secretion and T
      cell priming capacity of dendritic cells.
AB  - The nucleotide adenosine-5'-monophosphate (AMP) can be released by various cell
      types and has been shown to elicit different cellular responses. In the
      extracellular space AMP is dephosphorylated to the nucleoside adenosine which can
      then bind to adenosine receptors. However, it has been shown that AMP can also
      activate A(1) and A(2a) receptors directly. Here we show that AMP is a potent
      modulator of mouse and human dendritic cell (DC) function. AMP increased
      intracellular Ca(2+) concentration in a time and dose dependent manner.
      Furthermore, AMP stimulated actin-polymerization in human DCs and induced
      migration of immature human and bone marrow derived mouse DCs, both via direct
      activation of A(1) receptors. AMP strongly inhibited secretion of TNF-alpha and
      IL-12p70, while it enhanced production of IL-10 both via activation of A(2a)
      receptors. Consequently, DCs matured in the presence of AMP and co-cultivated
      with naive CD4(+)CD45RA(+) T cells inhibited IFN-gamma production whereas
      secretion of IL-5 and IL-13 was up-regulated. An enhancement of Th2-driven immune
      response could also be observed when OVA-pulsed murine DCs were pretreated with
      AMP prior to co-culture with OVA-transgenic naive OTII T cells. An effect due to
      the enzymatic degradation of AMP to adenosine could be ruled out, as AMP still
      elicited migration and changes in cytokine secretion in bone-marrow derived DCs
      generated from CD73-deficient animals and in human DCs pretreated with the ecto
      nucleotidase inhibitor 5'-(alpha,beta-methylene) diphosphate (APCP). Finally, the
      influence of contaminating adenosine could be excluded, as AMP admixed with
      adenosine desaminase (ADA) was still able to influence DC function. In summary
      our data show that AMP when present during maturation is a potent regulator of
      dendritic cell function and point out the role for AMP in the pathogenesis of
      inflammatory disorders.

PMID- 22624051
TI  - Personalized pathway enrichment map of putative cancer genes from next generation
      sequencing data.
AB  - BACKGROUND: Pathway analysis of a set of genes represents an important area in
      large-scale omic data analysis. However, the application of traditional pathway
      enrichment methods to next-generation sequencing (NGS) data is prone to several
      potential biases, including genomic/genetic factors (e.g., the particular disease
      and gene length) and environmental factors (e.g., personal life-style and
      frequency and dosage of exposure to mutagens). Therefore, novel methods are
      urgently needed for these new data types, especially for individual-specific
      genome data. METHODOLOGY: In this study, we proposed a novel method for the
      pathway analysis of NGS mutation data by explicitly taking into account the gene
      wise mutation rate. We estimated the gene-wise mutation rate based on the
      individual-specific background mutation rate along with the gene length. Taking
      the mutation rate as a weight for each gene, our weighted resampling strategy
      builds the null distribution for each pathway while matching the gene length
      patterns. The empirical P value obtained then provides an adjusted statistical
      evaluation. PRINCIPAL FINDINGS/CONCLUSIONS: We demonstrated our weighted
      resampling method to a lung adenocarcinomas dataset and a glioblastoma dataset,
      and compared it to other widely applied methods. By explicitly adjusting gene
      length, the weighted resampling method performs as well as the standard methods
      for significant pathways with strong evidence. Importantly, our method could
      effectively reject many marginally significant pathways detected by standard
      methods, including several long-gene-based, cancer-unrelated pathways. We further
      demonstrated that by reducing such biases, pathway crosstalk for each individual
      and pathway co-mutation map across multiple individuals can be objectively
      explored and evaluated. This method performs pathway analysis in a sample
      centered fashion, and provides an alternative way for accurate analysis of cancer
      personalized genomes. It can be extended to other types of genomic data
      (genotyping and methylation) that have similar bias problems.

PMID- 22624052
TI  - Effects of sodium azide on the abundance of prokaryotes and viruses in marine
      samples.
AB  - Flow cytometry is set to become the standard method for enumerating prokaryotes
      and viruses in marine samples. However, the samples need to be flash-frozen in
      liquid nitrogen directly after aldehyde fixation. Because liquid nitrogen may not
      always be available, we tested the potential of sodium azide as a preservative
      for prokaryotes and viruses in marine samples as a possible alternative. For that
      we conducted incubation experiments with untreated and sodium azide treated
      marine water samples at 4 degrees C and room temperature. The data indicate that
      sodium azide cannot be used to maintain marine samples used for the enumeration
      of prokaryotes and viruses.

PMID- 22624054
TI  - A unique regulator contributes to quorum sensing and virulence in Burkholderia
      cenocepacia.
AB  - Burkholderia cenocepacia causes chronic and life-threatening respiratory
      infections in immunocompromized people. The B. cenocepacia N-acyl-homoserine
      lactone (AHL)-dependent quorum sensing system relies on the production of AHLs by
      the synthases CepI and CciI while CepR, CciR and CepR2 control expression of many
      genes important for pathogenesis. Downstream from, and co-transcribed with cepI,
      lies BCAM1871 encoding a hypothetical protein that was uncharacterized prior to
      this study. Orthologs of B. cenocepacia BCAM1871 are uniquely found in
      Burkholderia spp and are conserved in their genomic locations in pathogenic
      Burkholderia. We observed significant effects on AHL activity upon mutation or
      overexpression of BCAM1871, although these effects were more subtle than those
      observed for CepI indicating BCAM1871 acts as an enhancer of AHL activity.
      Transcription of cepI, cepR and cciIR was significantly reduced in the BCAM1871
      mutant. Swimming and swarming motilities as well as transcription of fliC,
      encoding flagellin, were significantly reduced in the BCAM1871 mutant. Protease
      activity and transcription of zmpA and zmpB, encoding extracellular zinc
      metalloproteases, were undetectable in the BCAM1871 mutant indicating a more
      significant effect of mutating BCAM1871 than cepI. Exogenous addition of OHL
      restored cepI, cepR and fliC transcription but had no effect on motility,
      protease activity or zmpA or zmpB transcription suggesting AHL-independent
      effects. The BCAM1871 mutant exhibited significantly reduced virulence in rat
      chronic respiratory and nematode infection models. Gene expression and phenotypic
      assays as well as vertebrate and invertebrate infection models showed that
      BCAM1871 significantly contributes to pathogenesis in B. cenocepacia.

PMID- 22624053
TI  - Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling
      identifies key regulators of functional dynamics.
AB  - Deciphering functional mechanisms of the Hsp90 chaperone machinery is an
      important objective in cancer biology aiming to facilitate discovery of targeted
      anti-cancer therapies. Despite significant advances in understanding structure
      and function of molecular chaperones, organizing molecular principles that
      control the relationship between conformational diversity and functional
      mechanisms of the Hsp90 activity lack a sufficient quantitative characterization.
      We combined molecular dynamics simulations, principal component analysis, the
      energy landscape model and structure-functional analysis of Hsp90 regulatory
      interactions to systematically investigate functional dynamics of the molecular
      chaperone. This approach has identified a network of conserved regions common to
      the Hsp90 chaperones that could play a universal role in coordinating functional
      dynamics, principal collective motions and allosteric signaling of Hsp90. We have
      found that these functional motifs may be utilized by the molecular chaperone
      machinery to act collectively as central regulators of Hsp90 dynamics and
      activity, including the inter-domain communications, control of ATP hydrolysis,
      and protein client binding. These findings have provided support to a long
      standing assertion that allosteric regulation and catalysis may have emerged via
      common evolutionary routes. The interaction networks regulating functional
      motions of Hsp90 may be determined by the inherent structural architecture of the
      molecular chaperone. At the same time, the thermodynamics-based "conformational
      selection" of functional states is likely to be activated based on the nature of
      the binding partner. This mechanistic model of Hsp90 dynamics and function is
      consistent with the notion that allosteric networks orchestrating cooperative
      protein motions can be formed by evolutionary conserved and sparsely connected
      residue clusters. Hence, allosteric signaling through a small network of
      distantly connected residue clusters may be a rather general functional
      requirement encoded across molecular chaperones. The obtained insights may be
      useful in guiding discovery of allosteric Hsp90 inhibitors targeting protein
      interfaces with co-chaperones and protein binding clients.

PMID- 22624056
TI  - Genetic variation in the beta2-adrenocepter gene is associated with
      susceptibility to bacterial meningitis in adults.
AB  - Recently, the biased beta2-adrenoceptor/beta-arrestin pathway was shown to play a
      pivotal role in crossing of the blood brain barrier by Neisseria meningitidis. We
      hypothesized that genetic variation in the beta2-adrenoceptor gene (ADRB2) may
      influence susceptibility to bacterial meningitis. In a prospective genetic
      association study we genotyped 542 patients with CSF culture proven community
      acquired bacterial meningitis and 376 matched controls for 2 functional single
      nucleotide polymorphisms in the beta2-adrenoceptor gene (ADRB2). Furthermore, we
      analyzed if the use of non-selective beta-blockers, which bind to the beta2
      adrenoceptor, influenced the risk of bacterial meningitis. We identified a
      functional polymorphism in ADRB2 (rs1042714) to be associated with an increased
      risk for bacterial meningitis (Odds ratio [OR] 1.35, 95% confidence interval [CI]
      1.04-1.76; p = 0.026). The association remained significant after correction for
      age and was more prominent in patients with pneumococcal meningitis (OR 1.52, 95%
      CI 1.12-2.07; p = 0.007). For meningococcal meningitis the difference in genotype
      frequencies between patients and controls was similar to that in pneumococcal
      meningitis, but this was not statistically significant (OR 1.43, 95% CI 0.60
      3.38; p = 0.72). Patients with bacterial meningitis had a lower frequency of non
      selective beta-blockers use compared to the age matched population (0.9% vs.
      1.8%), although this did not reach statistical significance (OR 1.96 [95% CI 0.88
      4.39]; p = 0.09). In conclusion, we identified an association between a genetic
      variant in the beta2-adrenoceptor and increased susceptibility to bacterial
      meningitis. The potential benefit of pharmacological treatment targeting the
      beta2-adrenoceptor to prevent bacterial meningitis in the general population or
      patients with bacteraemia should be further studied in both experimental studies
      and observational cohorts.

PMID- 22624055
TI  - The African cichlid fish Astatotilapia burtoni uses acoustic communication for
      reproduction: sound production, hearing, and behavioral significance.
AB  - Sexual reproduction in all animals depends on effective communication between
      signalers and receivers. Many fish species, especially the African cichlids, are
      well known for their bright coloration and the importance of visual signaling
      during courtship and mate choice, but little is known about what role acoustic
      communication plays during mating and how it contributes to sexual selection in
      this phenotypically diverse group of vertebrates. Here we examined acoustic
      communication during reproduction in the social cichlid fish, Astatotilapia
      burtoni. We characterized the sounds and associated behaviors produced by
      dominant males during courtship, tested for differences in hearing ability
      associated with female reproductive state and male social status, and then tested
      the hypothesis that female mate preference is influenced by male sound
      production. We show that dominant males produce intentional courtship sounds in
      close proximity to females, and that sounds are spectrally similar to their
      hearing abilities. Females were 2-5-fold more sensitive to low frequency sounds
      in the spectral range of male courtship sounds when they were sexually-receptive
      compared to during the mouthbrooding parental phase. Hearing thresholds were also
      negatively correlated with circulating sex-steroid levels in females but
      positively correlated in males, suggesting a potential role for steroids in
      reproductive-state auditory plasticity. Behavioral experiments showed that
      receptive females preferred to affiliate with males that were associated with
      playback of courtship sounds compared to noise controls, indicating that acoustic
      information is likely important for female mate choice. These data show for the
      first time in a Tanganyikan cichlid that acoustic communication is important
      during reproduction as part of a multimodal signaling repertoire, and that
      perception of auditory information changes depending on the animal's internal
      physiological state. Our results highlight the importance of examining non-visual
      sensory modalities as potential substrates for sexual selection contributing to
      the incredible phenotypic diversity of African cichlid fishes.

PMID- 22624057
TI  - Effects of exogenous galanin on neuropathic pain state and change of galanin and
      its receptors in DRG and SDH after sciatic nerve-pinch injury in rat.
AB  - A large number of neuroanatomical, neurophysiologic, and neurochemical mechanisms
      are thought to contribute to the development and maintenance of neuropathic pain.
      However, mechanisms responsible for neuropathic pain have not been completely
      delineated. It has been demonstrated that neuropeptide galanin (Gal) is
      upregulated after injury in the dorsal root ganglion (DRG) and spinal dorsal horn
      (SDH) where it plays a predominantly antinociceptive role. In the present study,
      sciatic nerve-pinch injury rat model was used to determine the effects of
      exogenous Gal on the expression of the Gal and its receptors (GalR1, GalR2) in
      DRG and SDH, the alterations of pain behavior, nerve conduction velocity (NCV)
      and morphology of sciatic nerve. The results showed that exogenous Gal had
      antinociceptive effects in this nerve-pinch injury induced neuropathic pain
      animal model. It is very interesting that Gal, GalR1 and GalR2 change their
      expression greatly in DRG and SDH after nerve injury and intrathecal injection of
      exougenous Gal. Morphological investigation displays a serious damage after nerve
      pinch injury and an amendatory regeneration after exogenous Gal treatment. These
      findings imply that Gal, via activation of GalR1 and/or GalR2, may have
      neuroprotective effects in reducing neuropathic pain behaviors and improving
      nerve regeneration after nerve injury.

PMID- 22624058
TI  - Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human
      colostrum.
AB  - BACKGROUND: Generation of potent anti-HIV antibody responses in mucosal
      compartments is a potential requirement of a transmission-blocking HIV vaccine.
      HIV-specific, functional antibody responses are present in breast milk, and these
      mucosal antibody responses may play a role in protection of the majority of HIV
      exposed, breastfeeding infants. Therefore, characterization of HIV-specific
      antibodies produced by B cells in milk could guide the development of vaccines
      that elicit protective mucosal antibody responses. METHODS: We isolated B cells
      from colostrum of an HIV-infected lactating woman with a detectable
      neutralization response in milk and recombinantly produced and characterized the
      resulting HIV-1 Envelope (Env)-specific monoclonal antibodies (mAbs). RESULTS:
      The identified HIV-1 Env-specific colostrum mAbs, CH07 and CH08, represent two of
      the first mucosally-derived anti-HIV antibodies yet to be reported. Colostrum mAb
      CH07 is a highly-autoreactive, weakly-neutralizing gp140-specific mAb that binds
      to linear epitopes in the gp120 C5 region and gp41 fusion domain. In contrast,
      colostrum mAb CH08 is a nonpolyreactive CD4-inducible (CD4i) gp120-specific mAb
      with moderate breadth of neutralization. CONCLUSIONS: These novel HIV
      neutralizing mAbs isolated from a mucosal compartment provide insight into the
      ability of mucosal B cell populations to produce functional anti-HIV antibodies
      that may contribute to protection against virus acquisition at mucosal surfaces.

PMID- 22624060
TI  - QM/MM MD and free energy simulations of G9a-like protein (GLP) and its mutants:
      understanding the factors that determine the product specificity.
AB  - Certain lysine residues on histone tails could be methylated by protein lysine
      methyltransferases (PKMTs) using S-adenosyl-L-methionine (AdoMet) as the methyl
      donor. Since the methylation states of the target lysines play a fundamental role
      in the regulation of chromatin structure and gene expression, it is important to
      study the property of PKMTs that allows a specific number of methyl groups (one,
      two or three) to be added (termed as product specificity). It has been shown that
      the product specificity of PKMTs may be controlled in part by the existence of
      specific residues at the active site. One of the best examples is a Phe/Tyr
      switch found in many PKMTs. Here quantum mechanical/molecular mechanical (QM/MM)
      molecular dynamics (MD) and free energy simulations are performed on wild type
      G9a-like protein (GLP) and its F1209Y and Y1124F mutants for understanding the
      energetic origin of the product specificity and the reasons for the change of
      product specificity as a result of single-residue mutations at the Phe/Tyr switch
      as well as other positions. The free energy barriers of the methyl transfer
      processes calculated from our simulations are consistent with experimental data,
      supporting the suggestion that the relative free energy barriers may determine,
      at least in part, the product specificity of PKMTs. The changes of the free
      energy barriers as a result of the mutations are also discussed based on the
      structural information obtained from the simulations. The results suggest that
      the space and active-site interactions around the epsilon-amino group of the
      target lysine available for methyl addition appear to among the key structural
      factors in controlling the product specificity and activity of PKMTs.

PMID- 22624059
TI  - Purification and characterization of a novel hypersensitive response-inducing
      elicitor from Magnaporthe oryzae that triggers defense response in rice.
AB  - BACKGROUND: Magnaporthe oryzae, the rice blast fungus, might secrete certain
      proteins related to plant-fungal pathogen interactions. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we report the purification, characterization, and gene
      cloning of a novel hypersensitive response-inducing protein elicitor (MoHrip1)
      secreted by M. oryzae. The protein fraction was purified and identified by de
      novo sequencing, and the sequence matched the genomic sequence of a putative
      protein from M. oryzae strain 70-15 (GenBank accession No. XP_366602.1). The
      elicitor-encoding gene mohrip1 was isolated; it consisted of a 429 bp cDNA, which
      encodes a polypeptide of 142 amino acids with a molecular weight of 14.322 kDa
      and a pI of 4.53. The deduced protein, MoHrip1, was expressed in E. coli. And the
      expression protein collected from bacterium also forms necrotic lesions in
      tobacco. MoHrip1 could induce the early events of the defense response, including
      hydrogen peroxide production, callose deposition, and alkalization of the
      extracellular medium, in tobacco. Moreover, MoHrip1-treated rice seedlings
      possessed significantly enhanced systemic resistance to M. oryzae compared to the
      control seedlings. The real-time PCR results indicated that the expression of
      some pathogenesis-related genes and genes involved in signal transduction could
      also be induced by MoHrip1. CONCLUSION/SIGNIFICANCE: The results demonstrate that
      MoHrip1 triggers defense responses in rice and could be used for controlling rice
      blast disease.

PMID- 22624062
TI  - Temporal and spatial profiling of root growth revealed novel response of maize
      roots under various nitrogen supplies in the field.
AB  - A challenge for Chinese agriculture is to limit the overapplication of nitrogen
      (N) without reducing grain yield. Roots take up N and participate in N
      assimilation, facilitating dry matter accumulation in grains. However, little is
      known about how the root system in soil profile responds to various N supplies.
      In the present study, N uptake, temporal and spatial distributions of maize
      roots, and soil mineral N (N(min)) were thoroughly studied under field conditions
      in three consecutive years. The results showed that in spite of transient
      stimulation of growth of early initiated nodal roots, N deficiency completely
      suppressed growth of the later-initiated nodal roots and accelerated root death,
      causing an early decrease in the total root length at the rapid vegetative growth
      stage of maize plants. Early N excess, deficiency, or delayed N topdressing
      reduced plant N content, resulting in a significant decrease in dry matter
      accumulation and grain yield. Notably, N overapplication led to N leaching that
      stimulated root growth in the 40-50 cm soil layer. It was concluded that the
      temporal and spatial growth patterns of maize roots were controlled by shoot
      growth and local soil N(min), respectively. Improving N management involves not
      only controlling the total amount of chemical N fertilizer applied, but also
      synchronizing crop N demand and soil N supply by split N applications.

PMID- 22624061
TI  - Development and validation of Burkholderia pseudomallei-specific real-time PCR
      assays for clinical, environmental or forensic detection applications.
AB  - The bacterium Burkholderia pseudomallei causes melioidosis, a rare but serious
      illness that can be fatal if untreated or misdiagnosed. Species-specific PCR
      assays provide a technically simple method for differentiating B. pseudomallei
      from near-neighbor species. However, substantial genetic diversity and high
      levels of recombination within this species reduce the likelihood that molecular
      signatures will differentiate all B. pseudomallei from other Burkholderiaceae.
      Currently available molecular assays for B. pseudomallei detection lack rigorous
      validation across large in silico datasets and isolate collections to test for
      specificity, and none have been subjected to stringent quality control criteria
      (accuracy, precision, selectivity, limit of quantitation (LoQ), limit of
      detection (LoD), linearity, ruggedness and robustness) to determine their
      suitability for environmental, clinical or forensic investigations. In this
      study, we developed two novel B. pseudomallei specific assays, 122018 and 266152,
      using a dual-probe approach to differentiate B. pseudomallei from B.
      thailandensis, B. oklahomensis and B. thailandensis-like species; other species
      failed to amplify. Species specificity was validated across a large DNA panel
      (>2,300 samples) comprising Burkholderia spp. and non-Burkholderia bacterial and
      fungal species of clinical and environmental relevance. Comparison of assay
      specificity to two previously published B. pseudomallei-specific assays, BurkDiff
      and TTS1, demonstrated comparable performance of all assays, providing between
      99.7 and 100% specificity against our isolate panel. Last, we subjected 122018
      and 266152 to rigorous quality control analyses, thus providing quantitative
      limits of assay performance. Using B. pseudomallei as a model, our study provides
      a framework for comprehensive quantitative validation of molecular assays and
      provides additional, highly validated B. pseudomallei assays for the scientific
      research community.

PMID- 22624063
TI  - Disability, home physical environment and non-fatal injuries among young children
      in China.
AB  - OBJECTIVES: We compared the patterns of medically attended injuries between
      children with and without disabilities and explored the residential environment
      risks in five counties of Hubei Province in the People's Republic of China by a
      1:1 matched case-control study based on the biopsychosocial model of the
      International Classification of Functioning, Disability and Health--ICF. METHODS:
      1201 children aged 1-14 with disabilities and 1201 their healthy counterparts
      matched as having the same gender, same age, and lived in the same neighborhood
      were recruited in our study. Characteristics of injuries in the past 12 months
      were compared between children with and without disabilities. The associations
      among disability status, home environment factors and injuries were examined in
      logistic regression analysis taking into account sociodemographic factors.
      RESULTS: Children with disabilities had a significantly higher prevalence of
      injury than children without disabilities (10.2% vs. 4.4%; P<.001). The two
      groups differed significantly in terms of number of injury episodes, injury place
      and activity at time of injury. Falls were the leading mechanism of injury
      regardless of disability status. Most of the injury events happened inside the
      home and leisure activities were the most reported activity when injured for both
      groups. The univariate OR for injury was 4.46 (2.57-7.74) for the disabled
      children compared with the non-disabled children. Disabled children whose family
      raised cat/dog(s) were 76% more likely to be injured during the last 12 months
      (OR = 1.76; 95% CI = 1.02, 3.02), comparing with those whose family did not have
      any cat/dog. And for children without disabilities, those whose family had
      cat/dog(s) were over 3 times more likely to having injuries comparing with those
      whose family did not have any cat/dog. CONCLUSIONS: Children with disabilities
      had a significantly increased risk for injury. Interventions to prevent
      residential injury are an important public health priority in children with
      disabilities.

PMID- 22624064
TI  - Neuronatin in a subset of glioblastoma multiforme tumor progenitor cells is
      associated with increased cell proliferation and shorter patient survival.
AB  - Glioblastoma multiforme is the most common and malignant primary brain tumor.
      Recent evidence indicates that a subset of glioblastoma tumor cells have a stem
      cell like phenotype that underlies chemotherapy resistance and tumor recurrence.
      We utilized a new "multidimensional" capillary isoelectric focusing nano-reversed
      phase liquid chromatography platform with tandem mass spectrometry to compare the
      proteomes of isolated glioblastoma tumor stem cell and differentiated tumor cell
      populations. This proteomic analysis yielded new candidate proteins that were
      differentially expressed. Specifically, two isoforms of the membrane proteolipid
      neuronatin (NNAT) were expressed exclusively within the tumor stem cells. We
      surveyed the expression of NNAT across 10 WHO grade II and III gliomas and 23
      glioblastoma (grade IV) human tumor samples and found NNAT was expressed in a
      subset of primary glioblastoma tumors. Through additional in vitro studies
      utilizing the U87 glioma cell line, we found that expression of NNAT is
      associated with significant increases in cellular proliferation. Paralleling the
      in vitro results, when NNAT levels were evaluated in tumor specimens from a
      consecutive cohort of 59 glioblastoma patients, the presence of increased levels
      of NNAT were found to be a an independent risk factor (P = 0.006) for decreased
      patient survival through Kaplan-Meier and multivariate analysis. These findings
      indicate that NNAT may have utility as a prognostic biomarker, as well as a cell
      surface target for chemotherapeutic agents.

PMID- 22624065
TI  - Derivation of a myeloid cell-binding adenovirus for gene therapy of inflammation.
AB  - The gene therapy field is currently limited by the lack of vehicles that permit
      efficient gene delivery to specific cell or tissue subsets. Native viral vector
      tropisms offer a powerful platform for transgene delivery but remain nonspecific,
      requiring elevated viral doses to achieve efficacy. In order to improve upon
      these strategies, our group has focused on genetically engineering targeting
      domains into viral capsid proteins, particularly those based on adenovirus
      serotype 5 (Ad5). Our primary strategy is based on deletion of the fiber knob
      domain, to eliminate broad tissue specificity through the human coxsackie-and
      adenovirus receptor (hCAR), with seamless incorporation of ligands to re-direct
      Ad tropism to cell types that express the cognate receptors. Previously, our
      group and others have demonstrated successful implementation of this strategy in
      order to specifically target Ad to a number of surface molecules expressed on
      immortalized cell lines. Here, we utilized phage biopanning to identify a myeloid
      cell-binding peptide (MBP), with the sequence WTLDRGY, and demonstrated that MBP
      can be successfully incorporated into a knob-deleted Ad5. The resulting virus,
      Ad.MBP, results in specific binding to primary myeloid cell types, as well as
      significantly higher transduction of these target populations ex vivo, compared
      to unmodified Ad5. These data are the first step in demonstrating Ad targeting to
      cell types associated with inflammatory disease.

PMID- 22624066
TI  - Management of an occluded biliary metallic stent.
AB  - In patients with a malignant biliary obstruction who require biliary drainage, a
      self-expandable metallic stent (SEMS) provides longer patency duration than a
      plastic stent (PS). Nevertheless, a stent occlusion by tumor ingrowth, tumor
      overgrowth and biliary sludge may develop. There are several methods to manage
      occluded SEMS. Endoscopic management is the preferred treatment, whereas
      percutaneous intervention is an alternative approach. Endoscopic treatment
      involves mechanical cleaning with a balloon and a second stent insertion as stent
      in-stent with either PS or SEMS. Technical feasibility, patient survival and cost
      effectiveness are important factors that determine the method of re-drainage and
      stent selection.

PMID- 22624067
TI  - Endoscopic submucosal dissection for superficial esophageal neoplasms.
AB  - Endoscopic submucosal dissection (ESD) is currently accepted as the major
      treatment modality for superficial neoplasms in the gastrointestinal tract
      including the esophagus. An important advantage of ESD is its effectiveness in
      resecting lesions regardless of their size and severity of fibrosis. Based on
      excellent outcomes for esophageal neoplasms with a small likelihood of lymph node
      metastasis, the number of ESD candidates has increased. On the other hand, ESD
      still requires highly skilled endoscopists due to technical difficulties. To
      avoid unnecessary complications including perforation and postoperative
      stricture, the indications for ESD require careful consideration and a full
      understanding of this modality. This article, in the highlight topic series,
      provides detailed information on the indication, procedure, outcome,
      complications and their prevention in ESD of superficial esophageal neoplasms.

PMID- 22624069
TI  - Endoscopic papillary large balloon dilation after limited sphincterotomy for
      difficult biliary stones.
AB  - AIM: To assess the efficacy and safety of endoscopic papillary large balloon
      dilation after biliary sphincterotomy for difficult bile duct stones retrieval.
      METHODS: Retrospective review of consecutive patients submitted to the technique
      during 18 mo. The main outcomes considered were: efficacy of the procedure
      (complete stone clearance; number of sessions; need of lithotripsy) and
      complications. RESULTS: A total of 30 patients with a mean age of 68 +/- 10
      years, 23 female (77%) and 7 male (23%) were enrolled. In 10 patients, a single
      stone was found in the common bile duct (33%) and in 20 patients multiple stones
      (67%) were found. The median diameter of the stones was 17 mm (12-30 mm).
      Dilations were performed with progressive diameter Through-The-Scope balloons (up
      to 12, 15) or 18 mm. Complete retrieval of stones was achieved in a single
      session in 25 patients (84%) and in two sessions in 4 patients (13%). Failure
      occurred in 1 case (6%). Mechanical lithotripsy was performed in 6 cases (20%).
      No severe complications occurred. One patient (3%) had mild-grade post-endoscopic
      retrograde cholangiopancreatography (ERCP) pancreatitis. CONCLUSION: Endoscopic
      balloon dilatation with a large balloon after endoscopic sphincterotomy is a safe
      and effective technique that could be considered an alternative choice in
      therapeutic ERCP.

PMID- 22624070
TI  - Does capsule endoscopy have an added value in patients with perianal disease and
      a negative work up for Crohn's disease?
AB  - AIM: To investigate the role of capsule endoscopy in patients with persistent
      perianal disease and negative conventional work up for Crohn's disease (CD).
      METHODS: Patients with perianal disease (abscesses, fistulas, recurrent fissures)
      were evaluated for underlying CD. Patients who had a negative work up, defined as
      a negative colonoscopy with a normal ileoscopy or a normal small bowel series or
      a normal CT/MR enterography, underwent a Pillcam study of the small bowel after
      signing informed consent. Patients using nonsteroidal anti-inflammatory drugs or
      who had a history of inflammatory bowel disease or rheumatic disease were
      excluded. RESULTS: We recruited 26 patients aged 21-61 years (average 35.6
      years), 17 males and 9 females. One case could not be evaluated since the capsule
      did not leave the stomach. In 6 of 25 (24%) patients with a negative standard
      work up for Crohn's disease, capsule endoscopy (CE) findings were consistent with
      Crohn's disease of the small bowel. Family history of CD, white blood cell,
      hemoglobin, erythrocyte sedimentation rate or C-reactive protein did not predict
      a diagnosis of CD. Capsule endoscopy findings led to a change in treatment.
      CONCLUSION: In patients with perianal disease and a negative conventional work up
      to exclude CD, CE leads to incremental diagnostic yield of 24%.

PMID- 22624068
TI  - Endoscopic extraction of large common bile duct stones: A review article.
AB  - Since therapeutic endoscopic retrograde cholangiopancreatography replaced surgery
      as the first approach in cases of choledocolithiasis, a plethora of endoscopic
      techniques and devices appeared in order to facilitate rapid, safe and effective
      bile duct stones extraction. Nowadays, endoscopic sphincterotomy combined with
      balloon catheters and/or baskets is the routine endoscopic technique for stone
      extraction in the great majority of patients. Large common bile duct stones are
      treated conventionally with mechanical lithotripsy, while the most serious
      complication of the procedure is "basket and stone impaction" that is
      predominately resolved surgically. In cases of difficult, impacted, multiple or
      intrahepatic stones, more sophisticated procedures have been used.
      Electrohydraulic lithotripsy and laser lithotripsy are performed using
      conventional mother-baby scope systems, ultra-thin cholangioscopes, thin
      endoscopes and ultimately using the novel single use, single operator SpyGlass
      Direct Visualization System, in order to deliver intracorporeal shock wave energy
      to fragment the targeted stone, with very good outcomes. Recently, large balloon
      dilation after endoscopic sphincterotomy confirmed its effectiveness in the
      extraction of large stones in a plethora of trials. When compared with mechanical
      lithotripsy or with balloon dilation alone, it proved to be superior. Moreover,
      dilation is an ideal alternative in cases of altered anatomy where access to the
      papilla is problematic. Endoscopic sphincterotomy followed by large balloon
      dilation represents the onset of a new era in large bile duct stone extraction
      and the management of "impaction" because it seems that is an effective,
      inexpensive, less traumatic, safe and easy method that does not require
      sophisticated apparatus and can be performed widely by skillful endoscopists.
      When complete extraction of large stones is unsuccessful, the drainage of the
      common bile duct is mandatory either for bridging to the final therapy or as a
      curative therapy for very elderly patients with short life expectancy. Placing of
      more than one plastic endoprostheses is better while the administration of
      Ursodiol is ineffective. The great majority of patients with large stones can be
      treated endoscopically. In cases of unsuccessful stone extraction using balloons,
      baskets, mechanical lithotripsy, electrohydraulic or laser lithotripsy and large
      balloon dilation, the patient should be referred for extracorporeal shock wave
      lithotripsy or a percutaneous approach and finally surgery.

PMID- 22624071
TI  - Anesthetic management for small bowel enteroscopy in a World Gastroenterology
      Organization Endoscopy Training Center.
AB  - AIM: To study the anesthetic management of patients undergoing small bowel
      enteroscopy in the World Gastroenterology Organization (WGO) Endoscopy Training
      Center in Thailand. METHODS: Patients who underwent small bowel enteroscopy
      during the period of March 2005 to March 2011 in Siriraj Gastrointestinal
      Endoscopy Center were retrospectively analyzed. The patients' characteristics,
      pre-anesthetic problems, anesthetic techniques, anesthetic agents, anesthetic
      time, type and route of procedure and anesthesia-related complications were
      assessed. RESULTS: One hundred and forty-four patients underwent this procedure
      during the study period. The mean age of the patients was 57.6 +/- 17.2 years,
      and most were American Society of Anesthesiologists (ASA) class II (53.2%).
      Indications for this procedure were gastrointestinal bleeding (59.7%), chronic
      diarrhea (14.3%), protein losing enteropathy (2.6%) and others (23.4%).
      Hematologic disease, hypertension, heart disease and electrolyte imbalance were
      the most common pre-anesthetic problems. General anesthesia with endotracheal
      tube was the anesthetic technique mainly employed (50.6%). The main anesthetic
      agents administered were fentanyl, propofol and midazolam. The mean anesthetic
      time was 94.0 +/- 50.5 min. Single balloon and oral (antegrade) intubation was
      the most common type and route of enteroscopy. The anesthesia-related
      complication rate was relatively high. The overall and cardiovascular-related
      complication rates including hypotension in the older patient group (aged >= 60
      years old) were significantly higher than those in the younger group. CONCLUSION:
      During anesthetic management for small bowel enteroscopy, special techniques and
      drugs are not routinely required. However, for safety reasons anesthetic
      personnel need to optimize the patient's condition.

PMID- 22624072
TI  - Double-balloon endoscopy-diagnosed multiple small intestinal ulcers in a Churg
      Strauss syndrome patient.
AB  - Churg-Strauss syndrome (CSS) is a systemic vascular disorder characterized by
      severe bronchial asthma, hypereosinophilia, and allergic rhinitis. Small
      intestinal ulcers associated with CSS are a relatively rare manifestation that
      causes gastrointestinal bleeding. Multiple deep ulcers with an irregular shape
      are characteristic of small intestinal involvement of CSS. Video-capsule
      endoscopy (VCE), double-balloon endoscopy (DBE) and Spirus assisted enteroscopy
      have been developed recently and enabled observation of the small intestine. In
      this case report, we have described a patient with CSS who had multiple deep
      ulcers in the jejunum detected by oral DBE. Since severe gastrointestinal (GI)
      involvement has been identified as an independent factor associated with poor
      outcome, the careful investigation of GI tract must be needed for CSS patients
      with GI symptoms. We describe the usefulness of DBE for diagnosis of small
      intestinal ulcers in patient with CSS.

PMID- 22624073
TI  - Efferent limb of gastrojejunostomy obstruction by a whole okra phytobezoar: Case
      report and brief review.
AB  - A phytobezoar is one of the intraluminal causes of gastric outlet obstruction,
      especially in patients with previous gastric surgery and/or gastric motility
      disorders. Before the proton pump inhibitor era, vagotomy, pyloroplasty,
      gastrectomy and gastrojejunostomy were commonly performed procedures in peptic
      ulcer patients. One of the sequelae of gastrojejunostomy is phytobezoar
      formation. However, a bezoar causing gastric outlet obstruction is rare even with
      giant gastric bezoars. We report a rare case of gastric outlet obstruction due to
      a phytobezoar obstructing the efferent limb of the gastrojejunostomy site. This
      phytobezoar which consisted of a whole piece of okra (lady finger vegetable) was
      successfully removed by endoscopic snare. To the best of our knowledge, this is
      the first case of okra bezoar-related gastrojejunostomy efferent limb obstruction
      reported in the literature.

PMID- 22624074
TI  - Hispanic Fathers and Risk for Maltreatment in Father-Involved Families of Young
      Children.
AB  - The Hispanic population is the fastest growing segment of U.S. population.
      However, risks for child maltreatment in the foreign-born and native-born
      Hispanic populations are largely understudied. To address this knowledge gap, we
      explore the association of sociodemographic factors, psychosocial parenting
      factors, and nativity status with Hispanic fathers' aggression toward their young
      children (3 to 5 years). Using the Fragile Families and Child Wellbeing Study and
      the follow-up In-Home Longitudinal Study of Pre-School Aged Children, we examine
      data for 372 foreign-born (FB; n = 155) and native-born (NB; n = 217) Hispanic
      biological fathers residing in the home when the study target child was 3 years
      old. Results of analysis at the bivariate level show FB Hispanic fathers engage
      in fewer aggressive behaviors than NB Hispanic, White, or Black fathers. Time
      lagged path models of Hispanic fathers show FB Hispanic fathers use less
      aggression than NB Hispanic fathers. Length of time in the United States was not
      associated with parenting aggression. Path models also examine paternal
      psychosocial factors such as alcohol use, depression, parenting stress, and
      involvement in caregiving, and control for the child's aggressive behavior.
      Results suggest one reason Hispanic children do not face heightened risk for
      child welfare involvement, despite socioeconomic risks, is that FB Hispanic
      fathers use less aggression toward their young children. An implication of this
      finding is that socioeconomic and parenting behavior risks must be considered
      separately when practitioners are considering issues related to the
      representation of minority children in the child welfare system.

PMID- 22624076
TI  - The art of mothering.

PMID- 22624075
TI  - Acute Myocardial Infarction in a Young Adult Male Associated with the use of
      Smokeless Tobacco (Sweka).
AB  - Dipping smokeless tobacco (ST) is used worldwide. We report a case of acute
      myocardial infarction in a young patient, who consumed smokeless tobacco (Sweka)
      for over one year. ST may be as harmful as smoking and carries adverse cardiac
      complications. A prompt call for restriction and prohibition is advised and its
      alternative use to quit smoking must be abandoned.

PMID- 22624077
TI  - Austin flint (1812-1886).

PMID- 22624078
TI  - Healthy Ageing in Iranian Traditional Medicine's Resources in the Occasion of the
      World Health Day 2012.

PMID- 22624080
TI  - Applying an Educational-participatory Program based on the PRECEDE Model for
      Promoting Self-esteem and Mental Health of Students in Iran.
AB  - BACKGROUND: The students' vulnerability to different problems can have an impact
      on their mental health. Regarding the lack of evidence on the effectiveness of
      interventional programs based on health education planning models in this area in
      developing countries, an educational-participatory program based on the PRECEDE
      model was used, to promote the medical science students' self-esteem and mental
      health status, in Iran. METHODS: In this experimental study, 154 students from
      the universities of medical sciences in the north east of Iran were selected by
      stratified random sampling method. Then, they were randomly assigned to two
      groups of case and control. The questionnaires, including the enabling,
      reinforcing, and predisposing factors, the Rosenberg self-esteem scale, and the
      GHQ-28 were used for data collection. Then, an intervention plan, including focus
      group discussions and training of selected life skills, based on the PRECEDE
      model, was conducted for the case group. RESULTS: The predisposing, reinforcing,
      and enabling factors, and the self-esteem and mental health of the students
      showed a significant difference between the case and control groups. The Pearson
      correlation coefficient showed that there was a correlation between mental health
      and knowledge (P =0.008), between self-esteem and knowledge (P =0.02), self
      esteem and attitude (P =0.01), and mental health and attitude (P = 0.03).
      CONCLUSION: Health promotion planning by using life skills training based on the
      PRECEDE model can result in participation and empowerment, in order to promote
      the self-esteem and mental health of the students.

PMID- 22624079
TI  - Preventing a Cardiovascular Disease Epidemic among Indigenous Populations through
      Lifestyle Changes.
AB  - Cardiovascular disease (CVD) is the driving force behind the discrepancy in life
      expectancy between indigenous and non-indigenous groups in many countries.
      Preceding CVD many indigenous groups exhibit a cluster of cardiometabolic risk
      factors, including overweight-obesity, diabetes, high cholesterol, and high blood
      pressure. In turn, modifiable lifestyle risk factors contribute to the
      development of this cluster of cardiometabolic conditions. Modifiable lifestyle
      risk factors include, but are not limited to, physical inactivity, poor
      nutrition, excessive alcohol consumption, and cigarette smoking. Notably, these
      metabolic and lifestyle risk factors are relatively simple to monitor and track.
      The current review will look at modifiable cardiometabolic (overweight-obesity,
      diabetes mellitus, high cholesterol, and high blood pressure) and lifestyle
      (physical inactivity, poor nutrition, risky alcohol behavior, and cigarette
      smoking) risk factors among indigenous populations from Australia (Aboriginal
      Australians and Torres Strait Islanders), New Zealand (Maori) and the United
      States (Native Americans). Discussion will focus on the causal relationship
      between modifiable lifestyle risk factors and cardiometabolic outcomes, as well
      as, simple measurements for tracking these risk factors.

PMID- 22624081
TI  - Effectiveness of Community-based Intervention to Promote Iran's Food-based
      Dietary Guidelines.
AB  - BACKGROUND: Dietary Guidelines are considered as a useful tool for the promotion
      of healthy dietary behaviors. In Iran, despite the development of the latest
      National Food-Based Dietary Guidelines, in 2006, it has not been introduced at
      the community level yet. The present study aims to evaluate the effectiveness of
      an intervention program to promote Iran's Food-Based Dietary Guidelines (IFBDGs)
      in urban adult women. METHODS: A sample of 435 healthy women, aged 26 to 54
      years, was randomly assigned to the intervention or control groups. The
      intervention group was designed based on the Health Belief Model (HBM). Each
      subject in the intervention group received three sessions of group education on
      IFBDGs and the food guide pyramid and participated in a healthy cooking class.
      Dietary intake, cognitive outcomes related to the constructs of the HBM, physical
      activity, and the BMI were measured in both groups before, immediately, and one
      month after the intervention. The outcome measures were compared with the
      analysis of covariance (ANCOVA), by adjusting for baseline values. RESULTS: The
      intervention group had a significantly lower total daily energy intake than the
      control group after the intervention (P=.000). The adjusted differences in the
      changes of body mass index from the baseline were significant in both post
      intervention measurements in the intervention group compared to the controls.
      CONCLUSIONS: The intervention designed based on the Health Belief Model was
      effective in improving the adherence to FBDGs and could serve as a basic model
      for the promotion of healthy nutrition behavior among women in the primary health
      care setting.

PMID- 22624082
TI  - Diagnostic usefulness of transcutaneous bilirubinometry in very preterm newborns.
AB  - BACKGROUND: This study was performed to find out whether transcutaneous
      bilirubinometry could be a valid screening method for hyperbilirubinemia in
      preterm infants, especially for those who needed mechanical ventilation. METHODS:
      We evaluated 63 preterm Iranian newborns who were managed in the neonatal
      intensive care unit of Shahidbeheshti University Hospital, Isfahan, Iran from
      April 2009 to April 2010. Transcutaneous bilirubin (TCB) measurements were
      obtained using BiliCheck(TM) shortly before or 10 minutes after taking blood for
      determination of the plasma bilirubin level in premature newborns, who did not
      receive phototherapy. We assessed the correlation between the transcutaneous
      bilirubin and plasma bilirubin level by linear regression analysis. We also
      analyzed the gestational age, birth weight, postnatal age, sex, and hematocrit,
      for determination of their effect on transcutaneous bilirubin accuracy. RESULTS:
      The overall bilirubin concentration ranged from 5.4 to 17 mg/dL and from 4.8 to
      17.3 mg/dl for total serum bilirubin (TSB) and transcutaneous bilirubin,
      respectively. The mean values obtained by transcutaneous bilirubinometry were
      slightly higher than the total TSB values. The correlation coefficient between
      TSB and TCB was r=0.82, P<0.001, and this was not influenced by gestational age,
      postnatal age or hematocrit, which were previously considered to be important.
      The correlation coefficient between TSB and TCB in mechanically ventilated
      preterm infants was r=0.75, P<0.001. CONCLUSION: Plasma bilirubin level can be
      accurately measured by BiliCheck(TM) in premature newborns, even in newborns who
      need mechanical ventilation.

PMID- 22624083
TI  - The First Epidemic and New-emerging Human Fascioliasis in Kermanshah (Western
      Iran) and a Ten-year Follow Up, 1998-2008.
AB  - BACKGROUND: Fascioliasis is one of the most common zoonotic diseases in Iran and
      other parts of the world. Although the largest epidemic of this disease has
      occurred in northern provinces of Iran (Guilan) during the past two decades and a
      few cases have also been reported in Tehran and the other provinces, there has
      been no evidence of its' occurrence in western provinces of Iran such as
      Kermanshah before the outbreak which is being reported. METHODS: The study was
      conducted by teamwork of infectious disease specialist, parasitologist, general
      practitioner, entomologist, and laboratory technician. It is an "epidemic
      investigation" and a cross sectional descriptive one. Clinical data and para
      clinical changes are recorded considering all of the population of a village in
      Kangavar, one of the suburbs of Kermanshah (western Iran). RESULTS: The mean age
      was 21.65, (SD=12.44). Fifty three percent were female, and all of them were
      farmers. Eighty two percent had a history of watercress ingestion in a period of
      1-2 months before the admission and 18% consumed other vegetables. The average of
      eosinophils was 32.35% (SD=26). The patients' Enzyme Linked Immunosorbent Assay
      (ELISA) and Counter Current Immuno-electrophoresis (CCIE) serological tests were
      reported positive by the department of parasitology, Pasteur Institute of Iran.
      Treatment response to triclabendazole was excellent. A ten-year clinical and
      laboratory follow-up revealed no evidence of abnormality in treated patients.
      CONCLUSIONS: It was the first case of human fascioliasis in west Iran and was a
      real epidemic and an emerging infectious disease for this area at that time. The
      clinical symptoms were less severe compared with other reports. Health education
      to inhabitants and health care workers can lead to rapid detection of such
      outbreaks.

PMID- 22624084
TI  - Is routine duodenal biopsy necessary for the detection of celiac disease in
      patients presenting with iron deficiency anemia?
AB  - BACKGROUNDS: Iron deficiency anemia (IDA) is one of the well recognized
      presentations of celiac disease (CD). According to the lack of data from our
      population in this regard, we determined the prevalence of CD in patients
      presenting with IDA to see if it is worthwhile to do a precise screening for CD
      in such patients. METHODS: This cross-sectional study was conducted on patients
      referred with IDA to Poursina Hakim Gastroenterology Clinic, Isfahan (IRAN). All
      included patients underwent upper gastrointestinal endoscopy and duodenal biopsy.
      Histopathological changes were assessed according to the Marsh classification.
      Also, patients were evaluated for IgA anti-tissue transglutaminase (t-TG)
      antibody with enzyme-linked immunosorbent assay (ELISA) technique. CD was defined
      as having Marsh II or above histopathology or being seropositive with Marsh I
      histopathology and having a good response to gluten free diet (GFD). RESULTS:
      During the study, 130 patients with the mean age of 35.5+/-13.7 (67.7% female
      [20.4% post-menopausal]) were undergone seropathological studies. According to
      histopathological study and a clinical response to GFD, 13 patients (10%) were
      ultimately diagnosed with CD. Nine patients (6.9%) were seropositive, from which,
      five patients (3.8%) were ultimately diagnosed as CD cases. IgA anti-tTG became
      negative in all of these patients after six months of GFD. CONCLUSION: CD should
      be considered in any adult patient presenting with unexplained IDA, even if not
      accompanied with gastrointestinal symptoms. Routine duodenal biopsy performed
      during diagnostic upper gastrointestinal endoscopy is worthwhile in order to
      investigate for CD as an underlying cause of IDA in adult patients.

PMID- 22624085
TI  - The Influence of Individual and Contextual Socioeconomic Status on Obstetric Care
      Utilization in the Democratic Republic of Congo: A Population-based Study.
AB  - BACKGROUND: Maternal health care utilization continues to focus on the agenda of
      health care planners around the world, with high attention being paid to the
      developing countries. The devastating effect of maternal death at birth on the
      affected families is untold. This study examines the utilization of obstetric
      care in the Democratic Republic of Congo. METHODS: We have used the nationally
      representative data from the 2007. Democratic Republic of Congo Demographic and
      Health Survey. Multilevel regression analysis has been applied to a nationally
      representative sample of 6,695 women, clustered around 299 communities in the
      country. RESULTS: The results show that there are variations in the use of
      antenatal care and delivery care. Individual-level characteristics, such as
      women's occupation and household wealth status are shown to be associated with
      the use of antenatal care. Uptake of facility-based delivery has been seen to be
      dependent on the household wealth status, women's education, and partner's
      education. The effect of the neighborhoods' socioeconomic disadvantage on the use
      of antenatal care and facility-based delivery are the same. Women from highly
      socioeconomically disadvantaged communities, compared to their counterparts from
      less socioeconomically disadvantaged neighborhoods, are less likely to utilize
      both the antenatal services and healthcare facility for child delivery. The
      result of this study has shown that both individual and contextual socioeconomic
      status play an important role in obstetric care uptake. CONCLUSION: Thus,
      intervention aimed at improving the utilization of obstetrics care should target
      both the individual economic abilities of the women and that of their environment
      when considering the demand side.

PMID- 22624086
TI  - Vitamin B(12) Deficiency and Multiple Sclerosis; Is there Any Association?
AB  - BACKGROUND: Vitamin B(12) (Cobalamin) deficiency can result in some clinical and
      paraclinical characteristics similar to what is seen in multiple sclerosis (MS)
      patients. This study aimed to evaluate the controversial association between
      vitamin B(12) deficiency and MS. METHODS: We measured serum vitamin B(12) in 60
      patients with MS and 38 healthy controls. Clinical disability was evaluated
      according to the Extended Disability Status Scale (EDSS). Serum B(12)
      concentration was measured with Radioimmunoassay Dual Isotope method. The cutoff
      value for low serum vitamin B(12) concentrations was 75 pg/mL. Patients were in
      remission at the time of blood draw. RESULTS: There were 13 (21.6%) MS patients
      and 10 (26.3%) controls with low serum B(12) concentration with no significant
      difference between the groups; P>0.05. The mean serum vitamin B(12) concentration
      in MS patients (108.9+/-45.3 pg/mL) was not significantly different compared with
      controls (98.9+/-44.4 pg/mL); P=0.284. Likewise, there was no correlation between
      the concentration of serum vitamin B(12) and disease' age of onset, duration,
      subtypes, or disability status. CONCLUSIONS: In contrast to some previous
      reports, our findings did not support any association between B(12) deficiency
      and MS.

PMID- 22624087
TI  - Behavioral Addiction versus Substance Addiction: Correspondence of Psychiatric
      and Psychological Views.
AB  - INTRODUCTION: Behavioral science experts believe that all entities capable of
      stimulating a person can be addictive; and whenever a habit changes into an
      obligation, it can be considered as an addiction. Researchers also believe that
      there are a number of similarities as well as some differences between drug
      addiction and behavioral addiction diagnostic symptoms. The purpose of this study
      is to consider different approaches in this field. METHODS: This is a descriptive
      research using content analysis method. First, differences and similarities of
      various perspectives on addiction and addiction behavior in different substances
      were obtained, thereafter, the data was coded and categorized, subjects were
      discussed and major issues were extracted. RESULTS: Behavioral addiction such as
      internet addiction is similar to drug addiction except that in the former, the
      individual is not addicted to a substance but the behavior or the feeling brought
      about by the relevant action. In addition, the physical signs of drug addiction,
      are absent in behavioral addiction. Others have stated that behaviorally addicted
      individuals have certain symptoms and will undergo the same consequences brought
      about by addiction to alcohol and drugs as well as other obsessive behaviors.
      CONCLUSION: Similar to substance abuse prevention, programs aimed at addicted
      individuals and specialized training can educate adolescents about the warning
      signs of online addiction, in order to assist the early detection of this
      disorder. For prevention of behavioral addiction (such as internet addiction)
      authorities, cultural institutions and parents should monitor the use of internet
      and teach to the adolescent and children, the useful and appropriate methods of
      internet use.

PMID- 22624088
TI  - Acute Right Coronary Ostial Stenosis during Aortic Valve Replacement.
AB  - We report a rare case of acute right coronary artery stenosis developing in a
      patient undergoing aortic valve replacement. We present a case report with a
      brief overview of the literature relating to coronary artery occlusion associated
      with cardiac valve surgery - the theories and treatments are discussed. A 85 year
      old female was admitted under the care of the cardiothoracic team with signs and
      symptoms of heart failure. Investigations, including cardiac echocardiography and
      coronary angiography, indicated a critical aortic valve stenosis. Intraoperative
      right ventricular failure ensued post aortic valve replacement. Subsequent
      investigations revealed an acute occlusion of the proximal right coronary artery
      with resultant absence of distal flow supplying the right ventricle. An immediate
      right coronary artery bypass procedure was performed with resolution of the right
      ventricular failure. Subsequent weaning off cardiopulmonary bypass was uneventful
      and the patient continued to make excellent recovery in the postoperative phase.
      To our knowledge this is one of the few documented cases of intraoperative acute
      coronary artery occlusion developing during valve surgery. However, surgeons
      should be aware of the potential for acute occlusion so that early recognition
      and rapid intervention can be instituted.

PMID- 22624089
TI  - Determinants of Nutritional Status among Tribal Adolescent in Girls Paschim
      Medinipur District of West Bengal.

PMID- 22624090
TI  - Children contacting with smear positive tuberculosis patients.

PMID- 22624091
TI  - From wing to wing: the persistence of long ecological interaction chains in less
      disturbed ecosystems.
AB  - Human impact on biodiversity usually is measured by reduction in species
      abundance or richness. Just as important, but much more difficult to discern, is
      the anthropogenic elimination of ecological interactions. Here we report on the
      persistence of a long ecological interaction chain linking diverse food webs and
      habitats in the near-pristine portions of a remote Pacific atoll. Using
      biogeochemical assays, animal tracking, and field surveys we show that seabirds
      roosting on native trees fertilize soils, increasing coastal nutrients and the
      abundance of plankton, thus attracting manta rays to native forest coastlines.
      Partnered observations conducted in regions of this atoll where native trees have
      been replaced by human propagated palms reveal that this complex interaction
      chain linking trees to mantas readily breaks down. Taken together these findings
      provide a compelling example of how anthropogenic disturbance may be contributing
      to widespread reductions in ecological interaction chain length, thereby
      isolating and simplifying ecosystems.

PMID- 22624092
TI  - The network architecture of cortical processing in visuo-spatial reasoning.
AB  - Reasoning processes have been closely associated with prefrontal cortex (PFC),
      but specifically emerge from interactions among networks of brain regions. Yet it
      remains a challenge to integrate these brain-wide interactions in identifying the
      flow of processing emerging from sensory brain regions to abstract processing
      regions, particularly within PFC. Functional magnetic resonance imaging data were
      collected while participants performed a visuo-spatial reasoning task. We found
      increasing involvement of occipital and parietal regions together with caudal
      rostral recruitment of PFC as stimulus dimensions increased. Brain-wide
      connectivity analysis revealed that interactions between primary visual and
      parietal regions predominantly influenced activity in frontal lobes. Caudal-to
      rostral influences were found within left-PFC. Right-PFC showed evidence of
      rostral-to-caudal connectivity in addition to relatively independent influences
      from occipito-parietal cortices. In the context of hierarchical views of PFC
      organization, our results suggest that a caudal-to-rostral flow of processing may
      emerge within PFC in reasoning tasks with minimal top-down deductive
      requirements.

PMID- 22624093
TI  - What is new in critical illness and injury science? Benefits of co-induction
      anesthesia in supraglottic airway management.

PMID- 22624094
TI  - Sedation in intensive care unit: Is Dexmedetomidine the best choice?

PMID- 22624095
TI  - A retrospective analysis of maxillofacial injuries in patients reporting to a
      tertiary care hospital in East Delhi.
AB  - BACKGROUND AND AIM: Maxillofacial trauma is frequently encountered in the
      Accident and Emergency department of hospitals either as an isolated injury or as
      a part of multiple injuries to the head, neck, chest, and abdomen. This study
      aimed to assess retrospectively the profile of maxillofacial injuries in patients
      reporting to a tertiary care hospital in East Delhi. MATERIALS AND METHODS: The
      study was conducted in the Department of Dentistry, UCMS and GTB Hospital, Delhi.
      Dental case record sheets of 1000 medicolegal cases reporting to the hospital
      emergency were scrutinized and various demographic and epidemiologic factors,
      including the patient's age and gender, time and day of reporting, and the
      etiology and nature of injury were recorded. RESULTS: The peak incidence of
      maxillofacial injury was observed in the age group of 21-30 years, with males
      outnumbering females in all age groups. Maximum number of trauma cases reported
      in late evening hours, especially on weekends. Interpersonal assault was the
      primary etiological factor followed by road traffic accidents. Soft tissue
      injuries were very common and maxillofacial fractures, when present, were most
      frequently observed in the mandible followed by the midface. CONCLUSION: The
      changing trend of the etiology of maxillofacial injuries in East Delhi
      necessitates strict legislation against violence and education in alcohol abuse.
      Periodic review of driving skills and stricter implementation of traffic rules in
      this area is a must to minimize the physical, psychological, and emotional
      distress associated with maxillofacial trauma.

PMID- 22624096
TI  - Studying current status of intensive care services in Sri Lanka.
AB  - OBJECTIVE: To describe intensive care unit (ICU) facilities in Sri Lanka; to
      describe the pattern of admissions, case-mix and mortality; compare patient
      outcome against the various types of ICUs; and determine the adequacy and
      standards of training received by medical and nursing staff. MATERIALS AND
      METHODS: Observational study of multidisciplinary (general) and adult speciality
      ICUs in government sector hospitals. RESULTS: Hospitals studied had 1 ICU bed per
      100 hospital beds. Each bed catered to 70-90 patients over a year. Death rates
      were comparable in each level of hospital/ICU despite differences in resource
      allocation. Fifty to 60% of patients had their original problems related to
      medicine, while only 35% - 45% were surgical. Thirty two percent of medical
      patients and 15% of surgical patients died. More than 90% of ICUs had a multi
      monitor for each bed. Seventy seven percent of ICUs had one or more ventilators
      for each bed. Arterial blood gas (ABG) facilities were available in 83% of ICUs.
      There were serious inadequacies in the availability of facilities of 24 hour
      physiotherapy (available only in 36.7%), 24 hour in hospital Ultra Sonography
      (22.4%), electrolyte analyser in ICU (54.2%), haemodialysis / continuous renal
      replacement therapy (HD/CRRT) (41.7%), and Echocardiography. Medical Officers'
      training was anaesthetics dominated as opposed to a multidisciplinary training.
      There was a severe shortage of critical care trained nurses. CONCLUSIONS: Only
      limited evolution has taken place in intensive care over the past 5 years. The
      reasons for higher death rates in medical patients should be investigated
      further. Moving towards a multidisciplinary approach for training and provision
      of care for ICU patients is recommended.

PMID- 22624097
TI  - Comparison of ketamine with fentanyl as co-induction in propofol anesthesia for
      short surgical procedures.
AB  - BACKGROUND AND OBJECTIVE: A prospective randomized control study was conducted to
      compare and evaluate quality of anesthesia with ketamine or fentanyl as co
      induction with propofol. MATERIALS AND METHODS: Sixty ASA I or II, 18-50 year old
      patients who were scheduled for minor surgeries of short duration (<30 min
      anticipated duration) were selected. The patients were randomly allocated to
      group I and group II comprising 30 patients each. The patients of group I were
      given ketamine injection 0.5 mg/kg and group II patients fentanyl injection (1.5
      MUg/kg) as co-induction agent. Two minutes later, induction of anesthesia was
      given with inj propofol (2.5 mg/kg) and appropriate-sized laryngeal mask airway
      was inserted. The anesthesia was maintained with 60% N(2)O in O(2) and
      intermittent bolus of inj propofol (0.5 mg/kg) after observing significant
      changes in the heart rate, blood pressure, lacrimation, sweating, and abnormal
      movements. RESULTS: There was significant decrease (P<0.05) in the pulse rate,
      systolic and diastolic blood pressure at 1, 3, and 5 min in group II (fentanyl
      group) whereas the change was insignificant (P>0.05) at 10 min. CONCLUSION: It
      was observed that ketamine as premedicant was better than fentanyl with respect
      to hemodynamic stability and caused less adverse effects intraoperatively and
      postoperatively.

PMID- 22624098
TI  - Upper extremity deep vein thrombosis.
AB  - A 56-year-old female, recently (3 months) diagnosed with chronic kidney disease
      (CKD), on maintenance dialysis through jugular hemodialysis lines with a
      preexisting nonfunctional mature AV fistula made at diagnosis of CKD, presented
      to the hospital for a peritoneal dialysis line. The recently inserted indwelling
      dialysis catheter in left internal jugular vein had no flow on hemodialysis as
      was the right-sided catheter which was removed a day before insertion of the left
      sided line. The left-sided line was removed and a femoral hemodialysis line was
      cannulated for maintenance hemodialysis, and the next day, a peritoneal catheter
      was inserted in the operation theater. However, 3 days later, there was
      progressive painful swelling of the left hand and redness with minimal numbness.
      The radial artery pulsations were felt. There was also massive edema of forearm,
      arm and shoulder region on the left side. Doppler indicated a steal phenomena due
      to a hyperfunctioning AV fistula for which a fistula closure was done. Absence of
      relief of edema prompted a further computed tomography (CT) angiogram (since it
      was not possible to evaluate the more proximal venous segments due to edema and
      presence of clavicle). Ct angiogram revealed central vein thrombosis for which
      catheter-directed thrombolysis and venoplasty was done resulting in complete
      resolution of signs and symptoms. Upper extremity DVT (UEDVT) is a very less
      studied topic as compared to lower extremity DVT and the diagnostic and
      therapeutic modalities still have substantial areas that need to be studied. We
      present a review of the present literature including incidences, diagnostic and
      therapeutic modalities for this entity. DATA SOURCES: MEDLINE, MICROMEDEX, The
      Cochrane database of Systematic Reviews from 1950 through March 2011.

PMID- 22624099
TI  - Role of music in intensive care medicine.
AB  - The role of music in intensive care medicine is still unclear. However, it is
      well known that music may not only improve quality of life but also effect
      changes in heart rate (HR) and heart rate variability (HRV). Reactions to music
      are considered subjective, but studies suggest that cardio/cerebrovascular
      variables are influenced under different circumstances. It has been shown that
      cerebral flow was significantly lower when listening to "Va pensioero" from
      Verdi's "Nabucco" (70.4+3.3 cm/s) compared to "Libiam nei lieti calici" from
      Verdi's "La Traviata" (70.2+3.1 cm/s) (P<0,02) or Bach's Cantata No. 169 "Gott
      soll allein mein Herze haben" (70.9+2.9 cm/s) (P<0,02). There was no significant
      influence on cerebral flow in Beethoven's Ninth Symphony during rest (67.6+3.3
      cm/s) or music (69.4+3.1 cm/s). It was reported that relaxing music plays an
      important role in intensive care medicine. Music significantly decreases the
      level of anxiety for patients in a preoperative setting (STAI-X-1 score 34) to a
      greater extent even than orally administered midazolam (STAI-X-1 score 36)
      (P<0.001). In addition, the score was better after surgery in the music group
      (STAI-X-1 score 30) compared to midazolam (STAI-X-1 score 34) (P<0.001). Higher
      effectiveness and absence of apparent adverse effects make relaxing, preoperative
      music a useful alternative to midazolam. In addition, there is sufficient
      practical evidence of stress reduction suggesting that a proposed regimen of
      listening to music while resting in bed after open-heart surgery is important in
      clinical use. After 30 min of bed rest, there was a significant difference in
      cortisol levels between the music (484.4 mmol/l) and the non-music group (618.8
      mmol/l) (P<0.02). Vocal and orchestral music produces significantly better
      correlations between cardiovascular and respiratory signals in contrast to
      uniform emphasis (P<0.05). The most benefit on health in intensive care medicine
      patients is visible in classical (Bach, Mozart or Italian composers) music and
      meditation music, whereas heavy metal music or techno are not only ineffective
      but possibly dangerous and can lead to stress and/or life-threatening
      arrhythmias, particularly in intensive care medicine patients.

PMID- 22624101
TI  - Dexmedetomidine-ketamine sedation during upper gastrointestinal endoscopy and
      biopsy in a patient with Duchenne muscular dystrophy and egg allergy.
AB  - Sedation during invasive procedures provides appropriate humanitarian care as
      well as facilitating the completion of procedure. Although generally safe and
      effective, adverse effects may occur especially in patients with co-morbid
      diseases. In many cases, given its rapid onset and offset, propofol is chosen to
      provide sedation during various invasive procedures. We present a nine-year-old,
      45 kg child with Duchenne muscular dystrophy (DMD) who presented for
      esophagogastroduodenoscopy (EGD). Given the egg allergy, which was a relative
      contraindication to the use of propofol, and the potential risk of malignant
      hyperthermia due to DMD, a combination of dexmedetomidine and ketamine was used
      for procedural sedation. Dexmedetomidine was administered as a loading dose of 1
      MUg/kg along with a single bolus dose of ketamine (1 mg/kg). This was followed by
      a dexmedetomidine infusion at 0.5 MUg/kg/hour. The patient tolerated the
      procedure well and was discharged to home. Previous reports regarding the use of
      dexmedetomidine and ketamine for procedural sedation are reviewed and the
      potential efficacy of this combination is discussed.

PMID- 22624100
TI  - Delivering obstetrical critical care in developing nations.
AB  - Obstetrical critical care has not been able to achieve the same level of peaks in
      developing nations like India, as in the western countries. Numerous factors,
      including clinical and economical, have played a major role in widening the gap
      of quality care delivery in severely ill obstetric patients, between the two
      extreme worlds. Moreover, this wide gap can be, to a large extent, attributable
      to the lower literacy rates, paucity of research in obstetrical critical care,
      poverty, lack of awareness, and the sociocultural and behavioral factors
      prevalent in these developing nations. The most common indication for Intensive
      Care Unit (ICU) admission of such patients throughout the world is hemorrhage,
      both antepartum and postpartum. Hypertensive disorders, pre-eclampsia, and its
      related complications are also major contributory factors for such admissions.
      The pattern of the disease necessitating such admissions influences maternal
      mortality to a great extent. The present article reviews the most common
      indications of obstetrical admissions to the ICU, the challenges and obstacles in
      the treatment of severely ill obstetric patients, their possible outcome in the
      developing nations, room for improvement, and the need for a change in the system
      for better delivery of critical care obstetrical services.

PMID- 22624102
TI  - Stevens-Johnson syndrome induced by sodium valproate monotherapy.
AB  - A case of Stevens-Johnson syndrome following treatment with sodium valproate is
      presented here. A 20-year-old male was put on sodium valproate monotherapy for
      the migraine, with generalized epilepsy. He developed vesicles and bullae in the
      oral and nasal mucosa with conjunctivitis, after 10 days of treatment. The
      lesions resolved after treating with systemic steroids. This case has been
      presented because Stevens-Johnson syndrome with sodium valproate monotherapy has
      been very rarely reported.

PMID- 22624103
TI  - Nosocomial infections and antimicrobial resistance pattern in a tertiary referral
      hospital in Hamedan, Iran.

PMID- 22624104
TI  - Continuous flow left ventricular assist devices and gastrointestinal bleeding.

PMID- 22624105
TI  - Histological effects of chronic administration of efavirenz on lateral geniculate
      body of adult Wistar rats.
AB  - BACKGROUND: The effects of chronic administration of efavirenz commonly used as
      part of highly active antiretroviral therapy (HAART) for the treatment of Human
      Immunodeficiency Virus (HIV) type-1 on the weight of the brain and inferior
      colliculus of adult Wistar rats was carefully studied. METHODS AND MATERIALS: The
      rats of both sexes (n = 24), with average weight of 200g were randomly assigned
      into two treatment (A & B) (n=16) and Control (c) (n=8) groups. The rats in the
      treatment group received 600mg/70kg bogy weight of efavirenz dissolved in
      distilled water daily for 30days through the orogastric tube. The control group
      received equal volume of distilled through the same route. All rats were fed with
      grower's mash and given water liberally. The rats were sacrificed by cervical
      dislocation method on the thirty-first day of the experiment and the lateral
      geniculate body was carefully dissected out and quickly fixed in 10% formal
      saline for histological study. RESULTS: The findings indicate that rats in the
      treated group showed some cellular degenerative changes like sparse cellular
      population, pyknotic nuclei with some microcystic changes and edema in the stroma
      of the lateral geniculate body as compared to the control group. CONCLUSION:
      Chronic administration of efavirenz may have an adverse effect on the visual
      sensibilities by affecting the microanatomy of the lateral geniculate body of
      adult Wistar rats. It is recommended that further studies aimed at corroborating
      these observations be carried out.

PMID- 22624106
TI  - Quantitative real time PCR detection of Clostridium difficile growth inhibition
      by probiotic organisms.
AB  - BACKGROUND: Probiotic microorganisms are potential treatments for Clostridium
      difficile diarrheal disease (CDD) but better methods are needed to determine the
      relative potency of probiotic microorganisms against pathogenic organisms in
      mixed cultures. AIM: Quantify C. difficile in the presence of putative probiotic
      organisms using molecular methods to determine relative probiotic potency.
      MATERIALS AND METHODS: C. difficile strains were cultivated anaerobically. Serial
      dilutions of Lactobacillus cultures or microbial mixtures from kefir were co
      cultured with C. difficile for 48 hours. Bacterial DNA was extracted and qPCR was
      used to measure C. difficile toxin A gene, on the basis of cycle threshold (Ct)
      number. RESULTS: Strains of Lactobacillus (human and ATCC derived), and mixed
      cultures from commercial kefir were co-cultured with C. difficile. Lactobacillus
      and the microbial mixture from kefir were ranked in order of their potency in C.
      difficile growth inhibition. CONCLUSIONS: PCR allows facile quantification of C.
      difficle in the presence of other. The technique measures relative potency of
      over-the-counter probiotics and may predict human strains meriting probiotic
      status.

PMID- 22624107
TI  - Rural male health workers in Western Jamaica: Knowledge, attitudes and practices
      toward prostate cancer screening.
AB  - BACKGROUND: Statistics have shown that since 1988, a significant percentage of
      males are unwilling to seek medical care. The question is if they had the
      knowledge, worked in the health system and were educated, would this be any
      different? AIM: The current study aims to fill this void in the literature by
      examining the perception of rural male health workers (from the Western Region)
      about prostate examination, and why they are reluctant to inquire about the
      probability of having, or the likelihood of not having prostate cancer. MATERIALS
      AND METHODS: The study utilized primary cross-sectional data that was collected
      during February and March 2008 from 170 males (ages 29 years and older), health
      care workers who were employed in particular rural health institutions in Jamaica
      (i.e. Western Regional Health Authority). SPSS was used to analyze the data.
      RESULTS: When the respondents were asked "Have you ever heard about the screening
      procedure for prostate?" 71.2% indicated yes, but only 27.1% had got their
      prostate checked by a health practitioner. When respondents were asked to state
      what influenced their choice of not doing a digital rectal examination, 20.6%
      indicated comfort level; 9.4% stated the gender of the health practitioner, 5.3%
      mentioned fear and others did not respond. Of those who had the examination 2
      years ago, 96.5% did not state the choice of method. CONCLUSION: The current
      study is limited in terms of its generalizability to rural males or rural males
      in Western Jamaica, but it does provide an insight into the difficulty of men in
      breaking away from culture.

PMID- 22624108
TI  - Paradoxes in self-evaluated health data in a developing country.
AB  - BACKGROUND: Statistics showed that males reported fewer illnesses and greater
      mortality rates than females, but are outlived by approximately 6 years by their
      female counterparts, yet their self-rated health status is the same as that of
      females. AIMS: THIS STUDY EXAMINES THE FOLLOWING QUESTIONS: (1) Are there
      paradoxes in health disparity between the sexes in Jamaica? and (2) is there an
      explanation for the disparity outside of education, marital status, and area of
      residence? METHODS AND MATERIALS: The current study utilised a data set collected
      jointly by the Planning Institute of Jamaica and the Statistical Institute of
      Jamaica. The data set is a survey on the living conditions of Jamaicans. It was
      conducted between May and August of 2007. The JSLC is a modification of the World
      Bank's Living Standards Measurement Study. The sample size was 6,783 respondents,
      with a non-response rate being 26.2%. RESULTS: Good health status was correlated
      with self-reported illness (OR =0.23, 95% CI = 0.09-0.59), medical care-seeking
      behaviour (OR = 0.51, 95% CI = 0.36-0.72), age (OR = 0.96, 95% CI = 0.96-0.97),
      and income (OR = 1.00, 95% CI = 1.00-1.00). Self-reported illness is
      statistically correlated with sex (OR = 0.25, 95% CI = 0.10-0.62), head of
      household (OR = 0.33, 95% CI = 0.12-0.96), age (OR = 1.04, 95% CI = 1.01-1.07)
      and current good self-rated health status (OR = 0.32, 95% CI = 0.12-0.84).
      CONCLUSION: This paper highlights that caution must be used by researchers in
      interpreting self-reported health data of males.

PMID- 22624109
TI  - Self-rated health of the educated and uneducated classes in Jamaica.
AB  - BACKGROUND: Education provides choices, opportunities, access to resources and it
      is associated with an increased likelihood of higher income. Does this holds true
      in developing nations like Jamaica, and does the educated class experience
      greater self-rated health status than the uneducated classes? AIMS: The current
      study will identify the socio-demographic correlates of self-rated health status
      of Jamaicans, examine the effects of these variables, explore self-rated health
      status and self-reported diagnosed recurring illness among the educated and
      uneducated classes, compute mean income among the different educational types,
      and determine whether a significant statistical correlation exists between the
      different educational cohorts. MATERIALS AND METHODS: The current study utilised
      the data set of Jamaica Survey Living Conditions which is a cross-sectional
      survey. It is a national probability survey, and data were collected across the
      14 parishes of the island. Stratified random sampling techniques were used to
      draw the sample. RESULTS: Self-rated health statuses of respondents are
      correlated with age, income, crowding, sex, marital status, area of residence,
      and self-reported illness (es) - chi(2) = 1,568.4, P < 0.001. Respondents with
      tertiary level educations were most likely to be classified in the wealthiest 20%
      (53.4%) and there was no significant statistical difference between their health
      status and the lower educated classes. CONCLUSION: There is a need for a public
      health care campaign that is specifically geared towards the educated classes as
      their educational achievement is not translating itself into better health care
      seeking behaviour and health status than the uneducated classes.

PMID- 22624110
TI  - Bilateral myopic photorefractive keratectomy in a 14-year-old boy.
AB  - CONTEXT: Refractive surgery has been performed for more than 10 years. Laser
      assisted intrastromal keratomileusis (LASIK) and photorefractive keratectomy
      (PRK) may be used in accommodative esotropia either in adolescent or in adult
      patients. Some authors have shown that LASIK is safe, effective, and stable at 10
      years follow-up post-surgery. CASE REPORT: A 14-year-old boy was admitted to our
      outpatient department on 08-01-2008. Together with his parents he asked for both
      eyes to be operated on by myopic PRK. On September 5(th) 2008 a myopic PRK was
      performed on his right eye and on September 12(th) 2008 on his left eye. A Bausch
      & Lomb Z172 excimer laser was used to perform a Planoscan procedure on both eyes.
      Uncorrected visual acuity was 1.0 after both procedures. The patient did not
      suffer pain, haze or glare in postoperative follow-up. CONCLUSION: Apart from the
      surgical technique, the author raises questions about the ethics of this
      procedure in a young boy.

PMID- 22624111
TI  - Bilateral proliferating Brenner tumor of the ovary associated with recurrent
      urothelial carcinoma of the urinary bladder.
AB  - CONTEXT: Brenner tumors of ovary are relatively uncommon neoplasm. Most of them
      are benign and less than 5% are proliferating or borderline. The association
      between Brenner tumor of the ovary and papillary urothelial carcinoma of bladder
      is extremely rare. CASE REPORT: We describe an unusual case of proliferating
      bilateral Brenner tumor of the ovary with a highly recurrent low-grade papillary
      urothelial carcinoma of bladder. CONCLUSION: The immunohistopathological
      similarities of ovarian and bladder tumors and their association in the current
      case, may be coincidental but may reflect a common initiating event inducing
      similar pathogenesis changes in the epithelium of both organs. More cases are
      needed to be reported to better understand this association.

PMID- 22624112
TI  - Autoreactivity to sweat glands and nerves in clinical scabies infection.
AB  - CONTEXT: Skin changes in pregnancy can be categorized as 1)
      physiological/hormonal, 2) alterations in pre-existing skin diseases, or 3)
      represent development of new dermatoses, some of which may be pregnancy specific.
      CASE REPORT: We describe a 19 years old female at 27 weeks gestation who
      presented with a rash on the face and breast, with intense pruritis. Hematoxylin
      and eosin demonstrated Scabies mites within the epidermis, with an intense
      perivascular infiltrate of lymphohistiocytic cells around the superficial dermal
      blood vessels. By direct immunofluorescence (DIF), human fibrinogen was also
      detected in the perivascular areas. DIF also revealed deposits of human IgG and
      complement C5-9/MAC deposits in the sweat glands, as well as in nerves
      surrounding the sweat glands subjacent to the mites. Overexpression of ezrin and
      junctional adhesion molecule antibodies close to the scabies infection sites were
      also seen. CONCLUSION: Given that the hallmark of clinical scabies is intense
      pruritus and that very limited information is available regarding the
      pathophysiology of this symptom, we suggest that the itching sensation may be
      exacerbated by nerves and eccrine sweat glands in close proximity to the sites of
      infection.

PMID- 22624113
TI  - Squamous cell carcinoma arising from an epidermal inclusion cyst: A case report.
AB  - CONTEXT: Cutaneous epidermal cysts are common lesions, but fortunately, malignant
      transformation of their epithelium is rare. There are few case reports in the
      literature concerning malignant transformation of an epidermal cyst into squamous
      cell carcinoma. We present a case of squamous cell carcinoma arising from an
      epidermal inclusion cyst and describe the clinical and histopathologic findings.
      CASE REPORT: A tumour measuring 1.5cm was surgically excised. Based on the
      histopathologic findings of the tumour, this case was diagnosed as squamous cell
      carcinoma that arises in an epidermal cyst. Malignant change had not been
      suspected until histological examination revealed it. Nine months after tumour
      resection, the patient is free of disease. CONCLUSION: malignant transformation
      of an epidermal inclusion cyst is rare; this case illustrates the importance of
      routine histology in excision of epidermal cysts.

PMID- 22624114
TI  - Extra ocular sebaceous carcinoma of the thigh: A case report.
AB  - CONTEXT: Sebaceous cell carcinoma is a malignant neoplasm, rarely recognized in
      extra ocular sites. His prognosis depends of the precocity of the diagnosis. This
      neoplasm is aggressive in 29%; lymph node and visceral metastasis aren't rare.
      CASE REPORT: An 80-year-old male had an ulcerated and infected nodule located on
      the left thigh. The lesion appeared after five months ago. It suspected a
      squamous cell carcinoma. The histologic findings revealed an extra ocular
      sebaceous carcinoma. The patient died one month later due to heart insufficiency.
      CONCLUSION: extra ocular sebaceous carcinoma is a rare neoplasm. It has more
      difficulties of diagnosis because it has diverse clinical presentations as well
      as a variety of histologic patterns. We will discuss the incidence, clinical,
      histological and the prognosis of this aggressive neoplasm.

PMID- 22624115
TI  - Endemic pemphigus foliaceus over a century: Part I.
AB  - BACKGROUND: Endemic pemphigus foliaceus (EPF) is the only known autoimmune
      disease presenting in circumscribed geographic areas. AIM: We aim to provide
      information concerning the natural course of EPF, including systemic compromise
      in the presteroid era, which has been largely unavailable in the current medical
      literature.  MATERIAL #ENTITYSTARTX00026; METHODS: By a retrospective review of
      the literature we aim to compile and compare the focus of EPF and the current
      knowledge about them. The main aim of this review is to summarize our current
      knowledge of EPF, including data described almost one century ago; and, to
      include several unindexed reports, which may have not been available to many
      current scientists and health care personnel. RESULTS: Foci of EPF have been
      described in several Central American and South American countries, affecting
      predominately young people and Amerindians, with an additional female
      predilection. Although most cases have occurred in Brazil, some cases have been
      reported in Peru, Paraguay, El Salvador, and Venezuela. Another variant of EPF
      has been described in El Bagre, Colombia, affecting older men and a few post
      menopausal females. Finally, another type of EPF was described in nomadic tribes
      affecting females of child bearing age in Tunisia, Africa. CONCLUSION: Our
      understanding of EPF has been hampered by a lack of government attention to these
      diseases, especially in some South and Central American countries. Other factors
      that have made past studies of EPF difficult include 1) that the disease foci are
      often located in rural areas bordering the rain forest of underdeveloped
      countries; and 2) military conflicts in some of these areas.

PMID- 22624117
TI  - Preparation and evaluation of a novel therapeutic dairy-based drink for
      phenylketonuria.
AB  - BACKGROUND: People with phenylketonuria need to eat a special diet which contains
      a low level of phenylalanine. Most of these special diets have high protein
      levels which contain phenylalanine. Control of phenylalanine levels in the early
      years of life is crucial and remains important throughout childhood, especially
      for cognitive function and behavior. AIMS: The current study evaluated the
      biological and sensory properties of a novel dairy-based drink for patients with
      phenylketonuria (PKU). METHODS AND MATERIALS: The novel dairy-based drink was
      prepared by emulsifying corn germ oil with casein glycomacropeptide (GMP)
      solution in milk permeates. The chemical composition and sensory properties of
      the dairy-based drink were determined. In addition, the dairy-based drink was
      nutritionally evaluated using patient volunteers. These patients followed a
      strict diet limiting phenylalanine in their food. Phenylalanine levels were
      measured before and after three days of consuming the dairy-based drink. RESULTS:
      The results of the sensory evaluation showed that the product was ranked that
      there were decreases in "good" and was acceptable by all test panels and
      volunteers. Serum phenylalanine levels in all volunteers decreased between 30% -
      80%. CONCLUSIONS: The data obtained from the sensory evaluation and the decreases
      in serum phenylalanine levels encourage us to utilize this formulated dairy-based
      drink for therapeutic feeding of PKU patients.

PMID- 22624118
TI  - Self-reported health and medical care-seeking behaviour of uninsured Jamaicans.
AB  - BACKGROUND: On examination of the literature in Latin America and the Caribbean,
      and in particular Jamaica, no study could be found that investigated the health
      and health care-seeking behaviour of uninsured people. This study bridges the gap
      in the literature by evaluating uninsured Jamaicans' medical care-seeking
      behaviour and good health status.  MATERIAL #ENTITYSTARTX00026; METHOD: The study
      extracted a sample of 5,203 uninsured respondents 15 years and older from a
      national probability cross-sectional survey of 6,782 Jamaicans. Descriptive
      statistics were used to provide background information on the sample; cross
      tabulations evaluated bivariate analyses, and logistic regression was used to
      model health and medical care-seeking behaviour. RESULTS: Good health of
      uninsured Jamaicans is correlated -reported biological condition (OR =0.114, 95%
      CI = 0.090 -0 .145) followed by age (OR =0.952, 95% CI = 0.946- 0.959); gender
      (OR = 1.501, 95% CI = 1.221-1.845); consumption (OR = 1.000, 95% CI = 1.000
      1.000); social class (upper class OR = 0.563, 95% CI = 0.357-0.888); education
      (secondary and above OR = 0.622, 95%CI = 0.402-0.963), and area of residence
      (other towns OR = 1.351, 95% CI = 1.026-1.778). Medical care-seeking behaviour is
      associated with age (OR = 1.020, 95% CI = 1.006 - 1.033); poor health status (OR
      = 2.303, 95% CI = 1.533-3.461), and marital status (married OR = 0.518, 95% CI =
      0.325-0.824). CONCLUSION: The findings are far reaching and provide an
      understanding of the uninsured, and the information can be used to aid public
      health intervention and education programmes.

PMID- 22624116
TI  - Health-related quality of life and chronic obstructive pulmonary disease in North
      Carolina.
AB  - BACKGROUND: Comparisons of health-related quality of life (HRQOL) between persons
      with chronic obstructive pulmonary disease (COPD) and adults in the general
      population are not well described. AIMS: To examine associations between COPD and
      four measures of HRQOL in a population-based sample.  PATIENTS
      #ENTITYSTARTX00026; METHODS: These relationships were examined using data from
      13,887 adults aged >18 years who participated in the 2007 Behavioral Risk Factor
      Surveillance System (BRFSS) conducted in North Carolina (NC). Logistic regression
      was used to obtain adjusted relative odds (aOR). RESULTS: The age-adjusted
      prevalence of COPD among NC adults was 5.4% (standard error 0.27). Nearly half of
      adults with COPD reported fair/poor health compared with 15% of those without the
      condition (age-aOR, 5.5; 95% confidence interval [ CI] , 4.4 to 6.8). On average,
      adults with COPD reported twice as many unhealthy days (physical/mental) as those
      without the condition. The age-adjusted prevalence of >14 unhealthy days during
      the prior 30 days was 45% for adults with COPD and 17% for those without. The aOR
      of >14 unhealthy days was 1.7 (95% CI, 1.4 to 2.2) times greater among adults
      with COPD compared with those without. CONCLUSIONS: These results suggest COPD is
      independently associated with lower levels of HRQOL and reinforce the importance
      of preventing COPD and its complications through health education messages
      stressing efforts to reduce total personal exposure to tobacco smoke,
      occupational dusts and chemicals, and other indoor and outdoor air pollutants
      linked to COPD and early disease recognition. Our findings represent one of the
      few statewide efforts in the US and provide guidance for disease management and
      policy decision making.

PMID- 22624119
TI  - Effect of curcumin on quinpirole induced compulsive checking: An approach to
      determine the predictive and construct validity of the model.
AB  - BACKGROUND: Disorders of anxiety vary in severity to a wide extent, and obsessive
      compulsive disorder (OCD) persists as the fourth most common form of mental
      illness and is reported to be associated with memory impairment, necessitating
      effective means of treatment. AIM: To study the effect of curcumin on OCD.
      METHODS: The present study includes the determination of effect of curcumin at 5
      and 10 mg/kg in quinpirole (0.5 mg/kg) -induced model of OCD, memory retention
      and brain monoamine levels in rats. RESULTS: A significant improvement from the
      obsessive-compulsive symptoms induced by quinpirole was observed in curcumin
      treated rats; curcumin showed a protective effect on memory task. An increase in
      serotonin levels and a decrease in the dopamine levels were observed in curcumin
      treated rats. CONCLUSION: Curcumin treatment had shown a protective effect in OCD
      with considerable influence on brain monoamine levels, thus providing an evidence
      for the predictive and construct validity of the model.

PMID- 22624121
TI  - Sensitivity of a papanicolaou smear in the diagnosis of candida albicans
      infection of the cervix.
AB  - BACKGROUND: Candida albicans infections of the cervix are not adequately
      diagnosed in Papanicolaou smears when compared with culture in Sabouraud dextrose
      agar. METHODS: Cervical smears were collected from 1000, non-pregnant,
      asymptomatic women. The specimens were prepared using the Papanicolaou (Pap)
      smear method examined by microscopy and subsequently cultured in Sabouraud
      dextrose agar. RESULTS: The overall incidences of C. albicans in cervical smears
      cultured in Sabouraud dextrose agar was 30.10%, while the incidence in the Pap
      smears was 7.60%, making the sensitivity of Pap smears for the diagnosis of C.
      albicans to be 25.25%. Mild, and some moderate, infections detectable in
      Sabouraud dextrose agar could not be detected in the Pap smear specimens.
      Vulnerability to C. albicans infection decreased with age, the highest infection
      rate being between 20 and 39 years of age while the least was between 60 and 69
      years of age. Papanicolaou's method stained the nuclei, chromatin and nucleoli
      very well and enhanced differentiation between malignant and non-malignant cells.
      It also stained the cytoplasm and its contents such as keratin, vacuoles and
      granules and differentiated between acidophilic and basophilic materials. Non
      cellular substances such as fibrin, crystals and pigments were also stained using
      this method. In addition, Papanicolaou's method also stained some fungal and
      bacterial species, but did not provide differential staining characteristics seen
      in Gram staining technique. CONCLUSIONS: Papanicolaou stain should not be used as
      an alternative to culture in the diagnosis of Candida albicans.

PMID- 22624120
TI  - Social determinants of physical exercise in older men in Jamaica.
AB  - BACKGROUND:  BACKGROUND: Physical activity interventions have been demonstrated
      to improve health-related quality of life and to be of special benefit to older
      adults with specific chronic conditions including arthritis, hypertension,
      diabetes mellitus, and heart disease. AIM: This study examined the extent and
      social determinants of physical exercise in elderly men in Jamaica. MATERIALS AND
      METHODS: A sample of 2,000 men 55 years of age and older was extracted from a
      total of 33,674 males in the parish of St. Catherine. A 132-item questionnaire
      was used to collect the data. A stratified random sampling technique was used to
      draw the sample. Descriptive statistics were used to provide background
      information on the sub-sample, and logistic regressions were utilized to model
      physical exercise. RESULTS: Of the respondents, 55.4% indicated good health
      status, 51.0% lived in rural areas; 10.4% had moderate to high functional
      dependence and 67.3% reported that they did some form of physical exercise. Of
      those who indicated involvement in physical exercise (n = 1,345), 77.2% jogged,
      ran, and/or walked; 13.3% did aerobics; 4.7% swam; 2.0% cycled and 0.6% did push
      ups or sit-ups. The variables that predicted being engaged in physical exercise
      were education; age of respondents; current good health status; household head;
      health plan; employment status, and social support. CONCLUSION: Most of the
      elderly men were engaged in some form of physical activity and had good health.
      Age and good health status were the most influential social determinants of
      physical exercise. However, effective interventions to promote physical activity
      in older men in Caribbean countries such as Jamaica deserve wide implementation.

PMID- 22624122
TI  - Attitudes and perceived barriers of tertiary level health professionals towards
      incident reporting in Pakistan.
AB  - BACKGROUND: A limited framework of incident reporting exists in most of the
      health care system in Pakistan. This poses a risk to the patient population and
      therefore there is a need to find the causes behind the lack of such a system in
      healthcare settings in Pakistan. AIMS: To determine the attitudes and perceived
      barriers towards incident reporting among tertiary care health professionals in
      Pakistan MATERIALS AND METHODS: The study was done in Shifa International
      Hospitals and consisted of a questionnaire given to 217 randomly selected doctors
      and nurses. Mean +/- SD of continuous variables and frequency (percentage %) of
      categorical variables are presented. Chi square statistical analysis was used to
      test the significance of association among doctors and nurses with various
      outcome variables (motivators to report, perceived barriers, preferred person to
      report and patient's outcome that influence reporting behaviors). P value of
      <0.05 was considered significant. Student doctors and student nurses were not
      included in the study. RESULTS: Unlike consultant, registrars, medical officers
      and nurses (more than 95% are willing to report), only 20% of house officers will
      report the incident happened through them. Sixty nine percent of doctors and 67%
      of nurses perceive 'administration sanction' as a common barrier to incident
      reporting. Sixty percent of doctors and 80% of nurses would prefer reporting to
      the head of the department. CONCLUSIONS: By giving immunity from administrative
      sanction, providing prompt feedback and assurance that the incident reporting
      will be used to make changes in the system, there is considerable willingness of
      doctors and nurses to take time out of their busy schedules to submit reports.

PMID- 22624123
TI  - Vimentin compartmentalization in discoid lupus.
AB  - CONTEXT: Discoid lupus erythematosus (DLE) is a chronic skin condition, often
      presenting inflammatory, scarring lesions predominating on sun exposed areas of
      the face and scalp. CASE REPORT: A 46-year-old black female was evaluated for
      possible DLE. Biopsies for hematoxylin and eosin (H&E) and immunohistochemistry
      (IHC) examination, as well as for direct immunofluorescence (DIF) analysis were
      performed. The H&E staining demonstrated mild epidermal atrophy with focal
      follicular plugging. A mild interface infiltrate of lymphocytes and histiocytes
      and a superficial and deep, perivascular and periadnexal dermal infiltrate of
      lymphocytes, histiocytes and plasma cells was observed The DIF revealed strong
      deposits of immunoglobulins IgG, IgM, fibrinogen and Complement/C3, present in a
      granular pattern at the basement membrane junction (BMZ) of the skin as well as
      in the BMZ of the sebaceous glands. In addition, deposits of IgA surrounding the
      superficial dermal blood vessels were appreciated. The IHC displayed
      compartmentalization of vimentin around the BMZ of both the superrficial skin and
      sebaceous gland BMZs, as well as similar patterns of deposits of the same
      immunoglobulins, complement, and fibrinogen as visualized by DIF. CONCLUSIONS:
      Minimal attention has been given to the process of compartmentalization of the
      dermis in inflammatory skin conditions, including DLE. However, it seems that in
      addition to the classical immunoglobulin and complement "lupus band" deposits at
      the BMZ, an additional, orchestrated immunologic reorganization of the dermis
      surrounding the inflammatory process is also present. Such an immunologic
      reorganization of the dermis could play a significant role in the pathophysiology
      of this disorder.

PMID- 22624124
TI  - Mucinous carcinoma with axillary lymph node metastasis in a male breast: A case
      report.
AB  - CONTEXT: Pure mucinous carcinoma of the male breast is an extremely rare
      neoplasm. It is characterized by a lower incidence of metastatic nodal
      involvement and a higher survival rate than invasive ductal carcinomas. CASE
      REPORT: We report the case of a 75-year-old male who presented with a
      retroareolar mass of the right breast. The patient underwent radical mastectomy
      including right axillary lymph node dissection. The tumor was well demarcated and
      had a friable consistency with a gelatinous appearance. Histologically, the
      diagnostic of pure mucinous carcinoma with lymph node metastasis was performed.
      After surgery, the patient received chemotherapy, radiotherapy, and
      hormonotherapy (Tamoxifen). The patient remained free of disease for 36 months
      after surgery. CONCLUSION: Pure mucinous carcinoma of the male breast is a very
      rare tumor; in which axillary nodal disease is exceptional.

PMID- 22624125
TI  - Endemic pemphigus over a century: Part II.
AB  - BACKGROUND: Endemic pemphigus foliaceus (EPF) is an autoimmune disease,
      classically occurring in a restricted geographic area. Foci of EPF have been
      described in several Central and South American countries, often affecting young
      people and Amerindians, with some female predilection. Although most American EPF
      cases have been documented in Brazil, cases have been reported in Peru, Paraguay,
      El Salvador and Venezuela. An additional variant of EPF has been described in El
      Bagre, Colombia, (El Bagre-EPF) affecting older men and a few post-menopausal
      females. Finally, one additional type of EPF has been described in nomadic tribes
      affecting females of child bearing age in Tunisia, Africa. AIMS: The main aim of
      this review is to summarize current knowledge about autoantigens, and immunologic
      and genetic studies in EPF. MATERIAL AND METHODS: We utilized a retrospective
      review of the literature, aiming to compile and compare the multiple geographic
      foci of EPF. RESULTS: The primary autoantigens in EPF are still considered to be
      desmogleins in the case of the Tunisian and all American cases, in
      contradistinction to plakins and desmogleins in El Bagre-EPF. Although several
      autoantigens are been suggested, their biochemical nature needs further
      elucidation. Current knowledge still supports the concept that an antibody
      mediated immune response represents the principal pathophysiology in all variants
      of EPF. CONCLUSION: A strong genetic susceptibility appears to contribute to
      disease development in several people affected by these diseases; however, no
      specific genes have been confirmed at present. We conclude that further
      investigation is necessary to define these disorders immunologically and
      genetically.

PMID- 22624126
TI  - Patient care: Is interpersonal trust missing?
AB  - BACKGROUND: Health statistics and studies in the Caribbean have omitted
      interpersonal trust in their investigations. AIMS: This study will examine the
      effect of interpersonal trust and other conditions on psychosocial subjective
      wellbeing and self-reported health, in order to assess the significance of
      interpersonal trust, as well as other socio-demographic factors on health.
      MATERIALS AND METHOD: The current study utilized primary data commissioned by the
      Centre of Leadership and Governance, Department of Government, the University of
      West Indies, Mona, Jamaica, between July and August 2006. It was a nationally
      representative probability sampling survey. A sample of 1,338 respondents was
      interviewed with a detailed 166-item questionnaire. RESULTS: Generally, the
      psychosocial subjective wellbeing of Jamaicans was high (mean = 6.8 +/- 1.8), and
      self-reported health was moderately high (mean = 6.3 +/- 2.6). The current study
      has revealed that income, political system, subjective social class, employment
      status, and interpersonal trust determine psychosocial subjective wellbeing as
      well as self-reported health. Interpersonal trust accounted for between 9.4 to
      10.4% of the explanatory power of the wellbeing and self-reported health of
      Jamaicans. CONCLUSION: The current study highlights that the determinants of
      health include interpersonal trust. It is critical to point out here that trust
      must be taken into consideration in any evaluation of health statistics, as it is
      a factor of subjective wellbeing and health. It is within this context that
      clinicians need to incorporate interpersonal trust along with other conditions,
      as it is a part of the psychosocial determinants of health, subjective wellbeing,
      and health treatment.

PMID- 22624127
TI  - Histological effects of long term consumption of nutmeg on the medial geniculate
      body of adult Wistar rats.
AB  - BACKGROUND: Nutmeg is commonly used as a spice in various dishes, as components
      of teas and soft drinks or mixed in milk and alcohol. The effect of chronic
      consumption of nutmeg on the medial geniculate body of adult Wistar rats was
      carefully studied. AIM: The objective is to observe any possible histological
      changes. MATERIALS AND METHODS: Rats of both sexes (n = 24), with average weight
      of 200g were equally and randomly assigned into two treatment groups [A] and [B];
      and untreated Control group [C] of (n = 8) per group. The rats in the treatment
      groups [A] and [B] were respectively given 1g and 2g of nutmeg thoroughly mixed
      with the feeds on a daily basis for thirty-two days. The control group received
      equal amount of feeds daily without nutmeg added for the thirty-two days period.
      All rats were fed with grower's mash and given water liberally. The rats were
      sacrificed by cervical dislocation method on day thirty-three of the experiment,
      medial geniculate body was carefully dissected out from the brain and quickly
      fixed in 10% formol-saline for histological study. RESULTS: The findings indicate
      that rats in the treated groups (A & B) showed some cellular degenerative changes
      like hypertrophy, sparse cellular population, pyknotic nuclei with some
      microcystic changes, and vacuolation in the stroma of the treated medial
      geniculate body relative to those in the control group. CONCLUSION: Long term
      consumption of nutmeg may have adverse effect on microanatomy of medial
      geniculate body, which could negatively impact on the auditory sensibilities.
      Further research, including human observational studies, aimed at corroborating
      these observations is recommended.

PMID- 22624128
TI  - Celiac disease in native Indians from Brazil: A clinical and epidemiological
      survey.
AB  - BACKGROUND: Celiac disease has been described in populations from around the
      world, with recent data emphasizing the occurrence of the disease in ethnic
      minorities. There are only a few studies evaluating celiac disease in native
      Indians. AIMS: This study aimed to screen the anti-endomysial antibody (IgA-EmA)
      in Kaingang and Guarani Indians from southern Brazil, in order to establish a
      clinical serological evaluation of celiac disease in these individuals. MATERIAL
      AND METHODS: Serum samples from 321 individuals (125 male and 196 female; 4-86
      years old) from Mangueirinha Indigenous Reserve, State of Parana, Brazil, and 180
      non-Indigenous healthy individuals (62 male and 118 female; 2-81 years old) were
      analysed to the presence of anti-endomysial antibody class IgA by indirect
      immunofluorescence assay. Amongst the Indians, 158 were Kaingang, 98 Guarani and
      65 of mixed race. Indians presenting complaints of diarrhea (N=12) were also
      evaluated to the IgG class of anti-endomisyal antibody. RESULTS: None of the
      individuals showed positive results either to IgA or IgG anti-endomysial
      antibodies. CONCLUSIONS: Although the results indicate an absence of celiac
      disease in Kaingang and Guarani Indians, the authors call attention to the
      importance of following up indigenous children or adults presenting
      gastrointestinal complaints or other symptoms related to the disease.
      Consideration should be given to the genetic background of these individuals,
      allied to the inter ethnic marriages and the changing habits or occupational
      activities, that have gradually introduced diseases previously not described in
      indigenous populations.

PMID- 22624129
TI  - The effects of dancehall genre on adolescent sexual and violent behavior in
      Jamaica: A public health concern.
AB  - BACKGROUND: Research has shown that there is a direct correlation between the
      loud 'hard-core' music played on public transportation and the proliferation of
      sexual activities on these said transportations. AIM: To determine the extent to
      which dancehall music/genre impacts adolescent behavior. MATERIALS AND METHOD:
      The study is informed by quantitative and qualitative data, which were collected
      during the period February-May 2008. Convenience and judgmental sampling were
      used to target 100 subjects. RESULTS: Of the 100 adolescent cases (50 male, 50
      female), females (40%) were more likely to gravitate to sexually explicit lyrical
      content than their male counterparts (26%). Females (74%) were also more likely
      to act upon lyrical contents than males (46%). There was no significant
      difference where males (100%) and females (98%) subconsciously sings the
      dancehall lyrics even without hearing it; as well as inspire their dreams 64% and
      62% respectively. However, more females (74%) than males (46%) acted on lyrical
      contents of the dancehall genre. CONCLUSION: There is a correlation between hard
      core dancehall genre and the sexual and violent behavior of adolescents.

PMID- 22624130
TI  - Histological studies of the effects of monosodium glutamate of the fallopian
      tubes of adult female Wistar rats.
AB  - BACKGROUND: The effect of monosodium glutamate used as food additive on the
      fallopian tubes of adult Wistar rat was investigated. MATERIAL AND METHODS: Adult
      female Wistar rats (n=24) of average weight of 230g were randomly assigned into
      three groups A, B and C in each group (n=8). The treatment groups (A & B) were
      given 0.04mg/kg and 0.08mg/kg of monosodium glutamate thoroughly mixed with the
      growers' mash, respectively on a daily basis. The control group (C) received
      equal amount of feeds (Growers' mash) without monosodium glutamate added for
      fourteen days. The growers' mash was obtained from Edo Feeds and Flour Mill Ltd,
      Ewu, Edo State and the rats were given water liberally. The rats were sacrificed
      on day fifteen of the experiment. The fallopian tubes were carefully dissected
      out and quickly fixed in 10% buffered formaldehyde for routine histological
      procedures. RESULT: The histological findings in the treated groups showed
      evidence of cellular hypertrophy, degenerative and atrophic changes, and lysed
      red blood cells in lumen with the group that received 0.08mg/kg of monosodium
      glutamate more severe. CONCLUSION: MSG may have some deleterious effects on the
      fallopian tubes of adult female Wistar rats at higher doses and by extension may
      contribute to the causes of female infertility. It is recommended that further
      studies aimed at corroborating these findings be carried out.

PMID- 22624131
TI  - Cognitive functionality of older men in St. Catherine, Jamaica.
AB  - BACKGROUND: The scientific literature is replete with factors that influence the
      cognitive functionality of older men but no such study has been done in Jamaica.
      AIMS: In this study we report our findings on the cognitive functionality of
      three cohorts of older men in a rural area. This is the first data published on
      the cognitive functionality of older men from Jamaica. MATERIAL AND METHOD: The
      investigation was carried out with the administration of a 132-item
      questionnaire. The measure includes items on demographics, retirement and health
      status, the seeking and avoidance of medical care, health treatment, medication
      use, childhood illness, happiness and the mini-mental status examination. The
      measure was given to 2,000 men 55 years and older who were randomly selected from
      St. Catherine. RESULTS: THE MULTIVARIATE ANALYSIS OF THE MODEL REVEALED THREE
      SIGNIFICANT DETERMINANTS OF COGNITIVE FUNCTIONALITY: Age (OR = 0.346, 95% CI =
      0.206, 0.582), social support (OR = 0.683, 95% CI = 0.443, 1.053) and having
      children (OR = 2.42, 95% CI = 1.130, 5.183). There is a negative relationship
      between age and cognitive functionality and a positive relationship between
      having children and cognitive functionality. CONCLUSIONS: Our main conclusions
      are that the two significant determinants of cognitive functionality of older men
      (age and having children) in Jamaica are unique given the many determinants of
      cognitive functioning cited in the scientific literature. The plethora of factors
      points to the need for further research to understand the range of factors that
      influence the cognitive functionality of older Jamaicans.

PMID- 22624132
TI  - Crohn's disease of the appendix with enterocutaneous fistula post-appendicectomy:
      An approach to management.
AB  - CONTEXT: Isolated involvement of the appendix in Crohn's disease is reported to
      be 0.2% to 1.8%, and is usually associated with ileocaecal Crohn's disease in 25%
      of ileal and 50% of caecal disease. While appendicitis in a patient who was
      previously diagnosed to have ileocaecal Crohn's may be managed with
      appendicectomy and ileocaecal resection, appendicectomy alone when performed for
      appendicitis in a patient with unsuspected ileocaecal Crohn's disease could lead
      to postoperative complications including enterocutaneous fistula. CASE REPORT: A
      young female patient who underwent appendicectomy elsewhere for acute
      appendicitis presented to us with a persistent enterocutaneous fistula of 6 weeks
      duration. She had complained of general ill health and occasional altered bowel
      habits for 6 months prior to the acute appendicitis presentation. Our
      investigations, including a CT scan, suggested the possibility of ileocaecal
      Crohn's disease. She underwent excision of the enterocutaneous fistula and
      ileocaecal resection, and histopathology of the resected specimen confirmed
      Crohn's disease. In the postoperative period she received mesasalazine. When last
      seen 2 years later during her regular follow-up, she was found to be in good
      health. CONCLUSION: The possibility of ileocaecal Crohn's disease should be
      considered in patients presenting with unexplained postoperative enterocutaneous
      fistula following appendicectomy. A high index of clinical suspicion is required
      to make a prompt diagnosis and institute appropriate further treatment in form of
      ileocaecal resection.

PMID- 22624133
TI  - Intramuscular cysticercosis diagnosed on ultrasonography in thigh: A rare case
      report.
AB  - CONTEXT: Cysticercosis is an infection with the larval (cysticercus) stage of
      Taenia solium. It is difficult to diagnose cysticercosis on ultrasonography.
      Ultrasonography was done on Logiq 500 Pro machine with convex probe at 3.5 MHz
      frequency and diagnosed as cysticercosis with surrounding inflammation in the
      right vastus medialis muscle of thigh with a linear probe at 9.6 MHz frequency.
      In this case, we are discussing the role of high resolution sonography which
      helped in non-invasive diagnosis and treatment. CASE REPORT: A 12 years old male
      patient presented with a swelling on the medial aspect of the right thigh. There
      was complaint of pain in the right thigh for the last one week with history of
      fever since three days. On local examination, a single swelling of size
      approximately 4x5 cm in the right medial aspect of thigh was present. On
      ultrasonography there was a well defined isolated cystic lesion of size 3.3 * 2.5
      cm intermuscular area. We have successfully managed the patient conservatively
      with albendazole and steroids only. CONCLUSION: We conclude that intermuscular
      cystic swelling in thigh can be diagnosed on high resolution sonography with a
      great confidence to manage it conservatively. Cost of investigations also
      reduced. Ultrasonography plays an important role. Child is doing well in follow
      up.

PMID- 22624134
TI  - CARDIOVASCULAR RISK ASSESSMENT AND SUPPORT TECHNIQUES: Whole blood viscosity
      assessment issues I: Extrapolation chart and reference values.
AB  - BACKGROUND: There are many different methods for the assessment of whole blood
      viscosity, but not every pathology unit has equipment for any of the methods.
      However, a validated arithmetic method exists whereby whole blood viscosity can
      be extrapolated from haematocrit and total serum proteins. AIMS: The objective of
      this work is to develop an algorithm in the form of a chart by which clinicians
      can easily extrapolate whole blood viscosity values in their consulting rooms or
      on the ward. Another objective is to suggest normal, subnormal and critical
      reference ranges applicable to this method. MATERIALS AND METHODS: Whole blood
      viscosity at high shear stress was determined, from various possible pairs of
      haematocrit and total proteins. A chart was formulated so that whole blood
      viscosity can be extrapolated. After determination of two standard deviations
      from the mean and ascertainment of symmetric distribution, normal and abnormal
      reference ranges were defined. RESULTS: The clinicians' user-friendly chart is
      presented. Considering presumptive lower and upper limits, the continuum of
      <=14.28, 14.29 - 15.00, 15.01 - 19.01, 19.02 - 19.39 and >=19.40 (208 Sec(-1)) is
      obtained as reference ranges for critically low, subnormal low, normal, subnormal
      high and critically high whole blood viscosity levels respectively. CONCLUSION:
      This article advances a validated method to provide a user-friendly chart that
      would enable clinicians to assess whole blood viscosity for any patients who has
      results for full blood count and total proteins. It would make the assessment of
      whole blood viscosity costless and the neglect of a known cardiovascular risk
      factor less excusable.

PMID- 22624135
TI  - Markers of renal function tests.
AB  - BACKGROUND: The markers of renal function test assess the normal functioning of
      kidneys. These markers may be radioactive and non radioactive. They indicate the
      glomerular filtration rate, concentrating and diluting capacity of kidneys
      (tubular function). If there is an increase or decrease in the valves of these
      markers it indicates dysfunction of kidney. AIM: The aim of this review is to
      compare and analyze the present and newer markers of renal function tests which
      help in diagnosis of clinical disorders.  MATERIAL #ENTITYSTARTX00026; METHODS:
      An extensive literature survey was done aiming to compare and compile renal
      function tests makers required in diagnosis of diseases. RESULTS: Creatinine,
      urea, uric acid and electrolytes are makers for routine analysis whereas several
      studies have confirmed and consolidated the usefulness of markers such as
      cystatin C and beta-Trace Protein. CONCLUSION: We conclude that further
      investigation is necessary to define these biomarkers in terms of usefulness in
      assessing renal function.

PMID- 22624136
TI  - Perception of women on cancer screening and sexual behavior in a rural area,
      Jamaica: Is there a public health problem?
AB  - BACKGROUND: The Ministry of Health in Jamaica recommends that cervical cancer
      screening be undergo by women 25-54 years old. The age range is based on
      international standards, but this is in need for revision based on the parish of
      St. Thomas. AIMS: The study aimed to evaluate the perception and practice of Pap
      smear and the sexual practices of women in St. Thomas in order to aid policy.
      PATIENTS AND METHODS: This is a cross-sectional descriptive study of 210 women
      (15-54 years) from St. Thomas, Jamaica. RESULTS: Eighty eight percent of the
      sample had done a Pap smear and 24% indicated that they did this at least once
      every 12 months. The Pap smear results revealed that 83.2% of the sample was
      normal and 11.5% of the participants knew that their Pap smear was abnormal.
      Eighty percent of those with abnormal Pap smear were aged between 20-35 years.
      Sixty percent indicated that they did not believe they were infected with any
      STDs, but the Pap smear results showed that 76.4% of them had STDs. Eighty-three
      percent of the sample indicated having one sexual partner; 22.1% indicated that
      they began having sex before 15 years; 71% began having sex at 15-20 years; 76%
      of the sample used a condom and 12% reported that they had never practiced safe
      sex. CONCLUSION: This study finds that the age interval for conducting Pap smear
      screening should be lowered to 20 years for women in the parish of St. Thomas,
      Jamaica.

PMID- 22624137
TI  - Dietary intake is not associated to the metabolic syndrome in elderly women.
AB  - BACKGROUND: The metabolic syndrome is a complex metabolic disturbance due to an
      interaction between genetic factors, poor dietary habits and physical inactivity.
      AIMS: To investigate the role of dietary intake on the prevalence of the
      metabolic syndrome in a population of elderly, socially active women in Brazil.
      PATIENTS AND METHODS: A total of 284 women with mean age 69.3 +/- 6.3 years were
      evaluated in a cross-sectional retrospective study. The metabolic syndrome was
      diagnosed according to criteria of the International Diabetes Federation. The
      dietary intake was evaluated through a questionnaire for 24-hour dietary recall.
      The groups with or without the metabolic syndrome were compared for dietary
      intake and risk factors for metabolic syndrome by the multiple regression model
      adjusted for age, smoking, physical activity, educational level, total energy
      intake and fiber contents of the diet. The odds ratio for the presence of the
      metabolic syndrome was calculated for each nutrient by quartile for total energy
      intake adjusted by the residue method. RESULTS: The prevalence of metabolic
      syndrome was 32% in the sample. There was not found any association between
      dietary intake, including all macronutrients and several micronutrients, and the
      presence of metabolic syndrome. CONCLUSION: No associations were observed between
      nutritional factors and the prevalence of the metabolic syndrome in elderly
      women, a result possibly due to the fact that these factors have an influence in
      earlier phases of life, or to a recent modification of dietary habits, which
      however was not able to prevent the establishment of the syndrome.

PMID- 22624138
TI  - Histological effects of oral administration of nutmeg on the kidneys of adult
      Wister rats.
AB  - AIMS: The effects of oral administration of nutmeg commonly used as spice in
      various dishes, as components of teas and soft drinks or mixed in milk and
      alcohol on the kidneys of adult Wistar rats were carefully studied. MATERIAL AND
      METHODS: Rats of both sexes (n = 24), with average weight of 220g were randomly
      assigned into two treatments (A & B) of (n=16) and Control (c) (n=8) groups. The
      rats in the treatment groups (A & B) received 0.1g (500mg/kg body weight) and
      0.2g (1000mg/kg body weight) of nutmeg thoroughly mixed with the feeds
      respectively on a daily basis for forty-two days. The control group (c) received
      equal amount of feeds daily without nutmeg added for forty-two days. The growers'
      mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo state,
      Nigeria and the rats were given water liberally. The rats were sacrificed by
      cervical dislocation on the forty-third day of the experiment. The kidneys were
      carefully dissected out and quickly fixed in 10% buffered formaldehyde for
      routine histological study after hematoxylin and eosin method. RESULT: The
      histological findings in the treated sections of the kidneys showed distortion of
      the renal cortical structures, vacuolations appearing in the stroma and some
      degree of cellular necrosis, with degenerative and atrophic changes when compared
      to the control group. CONCLUSION: These findings indicate that oral
      administration of nutmeg may have some deleterious effects on the kidneys of
      adult Wistar rats at higher doses and by extension may affect its excretory and
      other metabolic functions. It is recommended that caution should therefore be
      advocated in the intake of this product and further studies be carried out to
      examine these findings.

PMID- 22624139
TI  - Histological effects of chronic administration of Phyllanthus amarus on the
      kidney of adult Wistar rat.
AB  - BACKGROUND: Phyllanthus amarus is commonly used for treatment such as in gastro,
      urogenital diseases and infection. However, it is speculated to have some toxic
      effects such as renal tubular damage. AIMS: This study was to investigate the
      histological effects of chronic administration of the herb on kidney of adult
      Wistar rats. MATERIAL AND METHODS: Rats of both sexes (n = 24), with average
      weight of 200g were randomly assigned into two treatments (A and B) and control
      (C) groups of 8 rats each. Rats in treatment groups (A) and (B) respectively
      received daily administration of 400mg and 800mg of aqueous Phyllanthus amarus,
      per 70kg body weight for 30days through the orogastric tube. The control group
      received distilled water through the same route. All rats were fed with grower's
      mash and given water liberally. The rats were sacrificed by cervical dislocation
      on the thirty-first day of the experiment and the kidneys were carefully
      dissected out and quickly fixed in 10% formal saline for histological study.
      RESULTS: The observations indicate that rats in the treated groups showed some
      varying degree of distortion and disruption in microanatomy of the kidney
      including interstitial oedema and tubular necrosis, when compared to the control
      section. CONCLUSION: This report provides further evidence that medicinal use of
      Phyllanthus amarus has a potential adverse effect. This warrants further studies
      to establish or rule out any untoward side-effect of chronic renal dysfunctions.

PMID- 22624140
TI  - The image of health status and quality of life in a Caribbean society.
AB  - BACKGROUND: Health is defined as the presence or absence of illness. This
      conceptualization of health status is dominant in health treatment and in
      fashioning the health care system. However, very little research has been done on
      how Jamaicans view health status and quality of life (QoL). AIMS: This article
      seeks to understand how Jamaicans conceptualize health status and QoL because
      definitional content has implications for their health. MATERIAL AND METHODS: The
      current study utilized two national cross-sectional probability surveys from the
      Centre for Leadership and Governance (CLG) which looked at QoL among other
      variables and the Jamaican Survey of Living Conditions (JSLC) which measured
      living standards including health status. The sample in both surveys was 8,120
      participants. RESULTS: The majority of the respondents in the CLG (54%) and the
      JSLC (82.2%) surveys reported good health status. There was a strong statistical
      relationship between area of residence and health status (P < 0.0001) unlike the
      relationship between area of residence and quality of life (P < 0.137). The
      respondents dichotomized health status and QoL and a significant relationship was
      found between both variables (P < 0.0001). The respondents' dichotomization of
      health status and QoL is explained by the significant relationship between health
      status and self reported illness (P < 0.0001) where respondents view health
      status as the absence or presence of illness, excluding QoL. CONCLUSION: Health
      status means the presence or absence of illness and excludes QoL which is not in
      keeping with previous findings. This distinction is culturally determined.

PMID- 22624141
TI  - Knee joint examinations by magnetic resonance imaging: The correlation of
      pathology, age, and sex.
AB  - AIMS: The aim of our study was to investigate the incidence and coexistence of
      multiple knee joint pathologies and the distribution of knee joint pathologies
      according to age and sex. PATIENTS AND METHODS: A retrospective analysis was
      performed using the clinical data of patients evaluated with magnetic resonance
      imaging (MRI) of the knee joint. Data from 308 patients examined between August
      2002 and July 2003 were included into this study. A Pearson correlation analysis
      was performed to examine the relationship between the pathological findings and
      the age and sex of the patients. RESULTS: The ages of the patients ranged between
      1 and 74 years (mean: 43.3 years). Age was significantly correlated with meniscal
      degeneration and tears, medial collateral ligament degeneration, parameniscal
      cyst, and chondromalacia patellae. There was a significant correlation between
      male gender and anterior cruciate ligament injury. Meniscal injury was
      significantly correlated with bursitis, as well as medial collateral ligament
      injury. Bone bruise was significantly correlated with medial collateral ligament
      injury, lateral collateral ligament injury, Baker's cyst, and anterior cruciate
      ligament injury. Chondromalacia patellae was significantly correlated with
      anterior cruciate ligament injury, patellae alta, and osteochondral lesion.
      Bursitis (in 53.2% of the patients) followed by grade-II meniscal degeneration
      (in 43% of the patients) were the most common knee pathologies observed by MRI.
      CONCLUSIONS: MRI findings of select knee pathologies are significantly correlated
      with each other and the age and sex of the patient.

PMID- 22624142
TI  - Mycobacterium gordonae pulmonary infection in an immunocompetent adult.
AB  - CONTEXT: Nontuberculous mycobacteria are non-communicable organisms and currently
      there are over 125 species. Nontuberculous mycobacteria are usually recovered
      from the environment and can cause disease through respiratory, cutaneous,
      parenteral and gastrointestinal exposure. CASE REPORT: We describe a case of a
      young, immunocompetent patient that developed symptomatic Mycobacterium gordonae
      pulmonary infection. A computed tomography of the chest revealed hilar
      lymphadenopathy and nodular densities on the left side. Definitive diagnosis was
      made by a culture of a transbronchial biopsy. Treatment consisted of a short
      course of rifampin and ethambutol, which resulted in a clinical and radiographic
      improvement. CONCLUSIONS: Mycobacterium gordonae is capable of causing clinically
      significant disease in both immunocompetent and immunosuppressed individuals.

PMID- 22624144
TI  - Ionic liquid-functionalized graphene for fabricating an amperometric
      acetylcholinesterase biosensor.
AB  - This work reports a sensitive amperometric biosensor for organophosphate
      pesticides (OPs) fabricated by modifying a glassy carbon electrode with
      acetylcholinesterase (AChE) immobilized on ionic liquid-functionalized graphene
      (IL-G). The functionalized graphene sheets had good dispersibility and long-term
      stability in various solvents. The as-prepared biosensor showed high affinity to
      acetylthiocholine (ATCl) with a Michaelis-Menten constant (K(m)) value of 0.77
      mM. Furthermore, based on the inhibition by OPs of the enzymatic activity of the
      immobilized AChE, and using carbaryl as a model compound, the inhibition of
      carbaryl was proportional to its concentration ranging from 0.0025 to 0.48 and
      0.48 to 1.42 MUg mL(-1) with a detection limit of 0.8 ng mL(-1) (S/N = 3). The
      developed biosensor exhibited a good performance for OPs detection, including
      good reproducibility and acceptable stability, which provided a new and promising
      tool for the analysis of enzyme inhibitors.

PMID- 22624143
TI  - Sacroiliitis due to Salmonella Typhi: A case report.
AB  - CONTEXT: Pyogenic infections of the sacroiliac joint are observed quite rarely.
      The most frequent causative microorganisms are Staphylococcus aureus,
      Streptococcus species, and Pseudomonas aeruginosa that are commonly found in
      patients under intravenous medication. In this paper, a rare sacroiliitis case
      that developed due to Salmonella Typhi is discussed. CASE REPORT: A woman at the
      age of twenty applied to our clinic with complaints of fever, headache and
      diarrhea with which she had been suffering for five days. On physical
      examination, she had a slight fever, with a body temperature of 38.6 degrees C.
      She was hospitalized, and Salmonella Typhi was isolated from her blood culture.
      Later on, the patient described pain during left hip movement. Diffusion-weighted
      magnetic resonance imaging and scintigraphic examinations revealed left
      sacroiliitis. CONCLUSION: Although sacroiliitis arising from Salmonella Typhi
      infection is a rare entity, it should not be ignored in patients who have a
      clinical history for sacroiliitis.

PMID- 22624145
TI  - Surface-assisted laser desorption-ionization mass spectrometry on titanium
      dioxide (TiO2) nanotube layers.
AB  - The paper reports on the use of a titanium oxide (TiO(2)) nanotube layer as a
      sensitive substrate for surface-assisted laser desorption-ionization mass
      spectrometry (SALDI-MS) of peptides and small molecules. The nanotube layers were
      prepared by electrochemical anodization of titanium foil. The optimized TiO(2)
      nanotubes morphology coupled to a controlled surface chemistry allowed desorption
      ionization (D/I) of a peptide mixture (Mix1) with a detection limit of 10
      femtomoles for the neurotensin peptide. The performance of the TiO(2) nanotubes
      for the D/I of small molecules was also tested for the detection of sutent, a
      small tyrosine kinase inhibitor, and verapamil. A detection limit of 50 fmol was
      obtained for these molecules, as compared to 500 fmol using classical matrix
      assisted laser desorption-ionization mass spectrometry (MALDI-MS). Both amorphous
      and anatase TiO(2) layers displayed a comparable performance for D/I of analyte
      molecules. In a control experiment, we have performed D/I of analyte molecules on
      a flat TiO(2) layer. The absence of signal emphasizes the role of the
      nanostructured substrate in the D/I process.

PMID- 22624146
TI  - Amperometric detection of hypoxanthine and xanthine by enzymatic amplification
      using a gold nanoparticles-carbon nanohorn hybrid as the carrier.
AB  - A novel gold nanoparticles-single-walled carbon nanohorn (GNPs-SWCNH) hybrid was
      synthesized for the construction of an amperometric biosensing platform. The GNPs
      SWCNH hybrid was stable in aqueous solution for at least two weeks, and was
      characterized with scanning electron microscopy, transmission electron
      microscopy, and electrochemical impedance spectroscopy. The average diameter of
      GNPs in situ synthesized on the SWCNH was 5-8 nm, and the good interaction
      between GNPs and SWCNH was confirmed by ultraviolet-visible absorption
      spectroscopy. The GNPs-SWCNH immobilized on a platinum electrode showed high
      electrochemical activity toward the oxidation of hydrogen peroxide and uric acid
      with low applied potentials. Combining with the enzymatic reaction of xanthine
      oxidase (XOx), a biosensor for hypoxanthine and xanthine was constructed. The XOx
      GNPs-SWCNH-based biosensor exhibited good responses to hypoxanthine and xanthine
      with the linear ranges of 1.5 to 35.4 and 2.0 to 37.3 MUM, and the detection
      limits of 0.61 and 0.72 MUM, respectively. The recovery test showed acceptable
      results. The gold nanoparticles functionalized carbon nanohorns provided a
      promising way to construct an electrochemical platform for sensitive biosensing.

PMID- 22624147
TI  - Sensitive and selective detection of glutathione based on resonance light
      scattering using sensitive gold nanoparticles as colorimetric probes.
AB  - In this paper, we reported the development of a highly sensitive and selective
      resonance light scattering (RLS) technique for glutathione using gold
      nanoparticle probes. The assay relies upon the distance-dependent optical
      properties of gold nanoparticles, the self-assembly of glutathione on gold
      nanoparticles, and the interaction of a 2 : 1 glutathione-Cu(2+) complex. In the
      presence of Cu(2+), glutathione could rapidly induce the aggregation of gold
      nanoparticles, thereby resulting in greatly enhanced RLS intensity and red-to
      blue (or purple) color change. The concentration of glutathione can be determined
      by the naked eye or a fluorescence spectrometer. Under the optical conditions,
      the detection of glutathione can be finished within 20 min, and the detection
      limit of 10 nM can be reached. The concentration range of the probe is 40-280 nM.
      The proposed method holds a specific selectivity toward glutathione and it is
      applied to the detection of glutathione in human serum with satisfactory results.
      In addition, the assay shows great potential application for disease-associated
      biomarkers, and it will meet the great demand for amino acid determination in
      fields such as food processing, biochemistry, pharmaceutical, and clinical
      analysis.

PMID- 22624148
TI  - Fluorogenic and chromogenic probe for rapid detection of a nerve agent simulant
      DCP.
AB  - A fluorogenic and visual probe was devised to detect diethyl chlorophosphate
      (DCP), a nerve agent simulant. The probe, N-(rhodamine B)-lactam-2-aminoethanol
      (RB-AE), undergoes oxazoline formation following phosphorylation in the presence
      of DCP, which gives rapid and clear fluorescence and color change in the assay
      solutions.

PMID- 22624150
TI  - Noncovalent surface grafting of uranium complexed cucurbit[5]uril oligomer onto
      palm shell powder: a novel approach for selective uranyl ion extraction.
AB  - Biomass - that is a new feather in your cap: palm shell powder was used as
      support for novel uranyl complexed cucurbit[5]uril oligomer to obtain a selective
      extractant for uranium. The key to the selectivity lies in the perfect
      environment of the two portals of cucurbit[5]uril for uranyl ion binding.

PMID- 22624149
TI  - Amplified quenching of electrochemiluminescence from CdS sensitized TiO2
      nanotubes by CdTe-carbon nanotube composite for detection of prostate protein
      antigen in serum.
AB  - This work reports an ECL immunoassay method for ultrasensitive detection of
      prostate protein antigen (PSA), by remarkably efficient energy-transfer induced
      electrochemiluminescence (ECL) quenching from the CdS nanoparticles (NPs)
      sensitized TiO(2) nanotube array (CdS-TiO(2) NTs) to the activated CdTe NPs
      functionalized multi-wall carbon nanotubes (CdTe-MWNTs) composite. The coupling
      of TiO(2) and CdS NPs results in a cathodic ECL intensity 14.7 times stronger
      than that of the pure TiO(2) NTs electrode, which could be efficiently quenched
      by the CdTe-MWNTs. The enhanced mechanism of TiO(2) NTs ECL by CdS NPs was
      studied in detail by cyclic voltammetry and ECL spectroscopy. The strong
      absorption of the CdTe-MWNTs in the wavelength range of 400-800 nm renders them
      highly efficient for ECL quenching labeled on anti-PSA antibody. Based on a
      sandwich structure, we developed an ECL immunoassay method for the sensitive and
      selective detection of PSA. The ECL intensity decrement was logarithmically
      related to the concentration of the PSA in the range of 1.0 fg mL(-1) to 10 pg
      mL(-1) with a detection limit of 1 fg mL(-1). Human serum samples were then
      tested using the proposed immunoassay with excellent correlations, suggesting
      that the proposed immunoassay method is of great promise in clinical screening of
      cancer biomarkers.

PMID- 22624151
TI  - Editorial--single entities.

PMID- 22624152
TI  - The prognostic value of N-terminal pro-brain natriuretic peptide in non-ST
      elevation acute coronary syndromes: a meta-analysis.
AB  - BACKGROUND: Precise risk stratification is important in patients with non-ST
      elevation acute coronary syndromes (NSTE-ACS) on determination for
      hospitalization and intensity of treatment. A meta-analysis was performed in
      studies of patients with NSTE-ACS to evaluate the predictive nature of elevated N
      terminal pro-brain natriuretic peptide (NT-proBNP). METHODS: Online searches were
      conducted using database to identify suitable studies. A summary of relative
      risks (RRs) for death and myocardial infarction (MI) was calculated using random
      effects modeling. We also calculated the pooled sensitivity, specificity,
      positive predictive value, and negative predictive value. RESULTS: Thirteen
      studies were included. Elevated NT-proBNP levels were significantly associated
      with mortality [RR 4.89; 95% confidence interval (CI) 3.85-6.22] and incidence of
      MI (RR 1.66; 95% CI 1.24-2.22). The sensitivity and specificity for MI was 69.1%
      (95% CI 66.6%-71.6%) and 43.6% (95% CI 42.9%-44.3%), respectively, along with the
      positive and negative predictive values for MI of 8.2% (95% CI 7.7%-8.7%) and
      95.1% (95% CI 94.6%-95.5%), respectively. CONCLUSIONS: Meta-analysis suggests
      that elevated NT-proBNP levels were associated with an increased risk for MI or
      death in patients with NSTE-ACS. Normal levels of NT-proBNP are certainly more
      helpful when selecting NSTE-ACS patients with likelihood for favorable outcomes.

PMID- 22624153
TI  - Separate structural and functional domains of Tn4430 transposase contribute to
      target immunity.
AB  - Like other transposons of the Tn3 family, Tn4430 exhibits target immunity, a
      process that prevents multiple insertions of the transposon into the same DNA
      molecule. Immunity is conferred by the terminal inverted repeats of the
      transposon and is specific to each element of the family, indicating that the
      transposase TnpA is directly involved in the process.However, the molecular
      mechanism whereby this protein promotes efficient transposition into permissive
      targets while preventing transposition into immune targets remains unknown. Here,
      we demonstrate that both functions of TnpA can be uncoupled from each other by
      isolating and characterizing mutants that are proficient in transposition (T+)
      but impaired in immunity (I-). The identified T+/I- mutations are clustered into
      separate structural and functional domains of TnpA, indicating that different
      activities of the protein contribute to immunity.Combination of separate
      mutations had synergistic effects on target immunity but contrasting effects on
      transposition. One class of mutations was found to stimulate transposition,
      whereas other mutations appeared to reduce TnpA activity. The data are discussed
      with respect to alternative models in which TnpA acts as a specific determinant
      to both establish and respond to immunity.

PMID- 22624154
TI  - Retraction notice. "Antidepressant medication prevents suicide in depression".

PMID- 22624155
TI  - Commentary on Educational outcomes associated with providing a comprehensive
      guidelines program about nursing care of preterm neonates receiving total
      parenteral nutrition.

PMID- 22624156
TI  - A tool for every task, for every task a tool.

PMID- 22624157
TI  - How to get house staff involved in QI and safety.

PMID- 22624158
TI  - Hospital achieves consistent success.

PMID- 22624159
TI  - TJC begins advanced certification for hospice.

PMID- 22624160
TI  - Joint Commission gives HAIs own web portal.

PMID- 22624161
TI  - [2010 AIAC Guidelines for the management and treatment of atrial fibrillation].

PMID- 22624182
TI  - Alignment-free sequence comparison for biologically realistic sequences of
      moderate length.
AB  - The D(2) statistic, defined as the number of matches of words of some pre
      specified length k, is a computationally fast alignment-free measure of
      biological sequence similarity. However there is some debate about its
      suitability for this purpose as the variability in D(2) may be dominated by the
      terms that reflect the noise in each of the single sequences only. We examine the
      extent of the problem and the effectiveness of overcoming it by using two mean
      centred variants of this statistic, D(2)* and D(2c). We conclude that all three
      statistics are potentially useful measures of sequence similarity, for which
      reasonably accurate p-values can be estimated under a null hypothesis of
      sequences composed of identically and independently distributed letters. We show
      that D(2) and D(2)c, and to a somewhat lesser extent D(2)*, perform well in tests
      to classify moderate length query sequences as putative cis-regulatory modules.

PMID- 22624183
TI  - Hydroalcoholic extracts of Indian medicinal  plants can help in amelioration from
      oxidative  stress through antioxidant properties.
AB  - The in vitro study of the antioxidant properties of the hydroalcoholic extracts
      of various Indian medicinal plants can logically help to develop a better and
      safer way of amelioration from oxidative stress. As aimed, the present study has
      been done to estimate and thereby conclude regarding the antioxidant activities
      of a few Indian medicinal plants, viz., Terminalia chebula, Terminalia belerica,
      Emblica officinalis, Caesalpinia crista, Cajanus cajan, and Tinospora cordifolia.
      The extracts of the plants have been subjected to the evaluation of antioxidant
      properties through scavenging assays for reactive oxygen species like superoxide,
      nitric oxide, peroxynitrite, hypochlorous acid, singlet oxygen, etc. and
      measurement of TEAC values and other phytochemical parameters. The phenolic and
      flavonoid contents of each plant have been found to be correlated to their
      individual antioxidant activity. The results showed the hydroalcoholic extracts
      of the plants were efficient indicators of their antioxidant capacity thus
      concreting their basis to be used as natural antioxidant.

PMID- 22624184
TI  - Antioxidant potential and protection of pancreatic beta- cells by Calotropis
      gigantea in streptozocin induced diabetic rats.
AB  - This study was designed to examine the antioxidant defense by chloroform extract
      of Calotropis gigantea on streptozotocin-(40mg/kg, intraperitonial, single
      injection) induced diabetes in wistar albino rats. The extract significantly (P <
      .05) decreased the pancreatic thiobarbituric acid-reactive substances (TBARS)
      levels and significantly (P < .05) increased the superoxide dismutase, catalase,
      and glutathione levels as compared to above levels in pancreatic tissue of
      pathogenic diabetic rats. The results of test drug were comparable to
      Glibenclamide (5mg/kg, daily), a standard antihyperglycemic agent. The study
      concludes that Calotropis gigantea enhances the antioxidant defense against
      reactive oxygen species produced under hyperglycemic condition and this protects
      beta-cells against loss, and exhibit antidiabetic property.

PMID- 22624185
TI  - [The "historical realm of experience" of natural history and biology].

PMID- 22624186
TI  - [Ways of transcultural analysis: an essay on the    paradigm shift in 20th
      century Euro-American social and cultural anthropology].

PMID- 22624187
TI  - "Lodore" and the novel of society.

PMID- 22624188
TI  - Monstrous stepmother: Mary Shelley and Mary Jane Godwin.

PMID- 22624189
TI  - Mrs. Brown by Windsor's other widow.

PMID- 22624191
TI  - Warriors in politics: religious nationalism, masculine Hinduism and the Shiv Sena
      in Bombay.

PMID- 22624190
TI  - Polysexualities and romantic generations in Mary Shelley's mythological dramas
      "Midas" and "Proserpine".

PMID- 22624193
TI  - Reviving aid.

PMID- 22624194
TI  - Intestinal failure and the ward nurses: causes, assessment and management.
AB  - In order to manage intestinal failure (IF), a complex regimen of care is required
      to manage fluid intake and electrolyte balance. In the majority of cases ward
      nurses will bare the responsibility of managing patients with these specific
      needs, with the support of the nutritional multidisciplinary team. Therefore,
      nurses need to ensure they have expert knowledge of each area of IF management.
      This article defines IF and outlines how it can be managed surgically and
      medically. The author discusses the role of the ward nurse in monitoring and
      managing therapy, and states the importance of providing emotional and
      psychological care.

PMID- 22624195
TI  - Australia's biosecurity report card.

PMID- 22624196
TI  - Why we love being country vets--Walwa Veterinary Practice.

PMID- 22624197
TI  - Delivering optimal patient care through effective communication.

PMID- 22624198
TI  - Multiple anthropogenic stressors and the structural properties of food webs.
AB  - Coastal environments are among the most productive on the planet, providing a
      wide range of ecosystem services. Development and exploitation mean that they are
      faced with stresses from a number of anthropogenic sources. Such stresses are
      typically studied in isolation, but multiple stressors can combine in unexpected
      ways to alter the structure of ecological systems. Here, we experimentally
      explore the impacts of inorganic nutrients and organic matter on a range of food
      web properties. We find that these two stressors combine additively to produce
      significant increases in connectance and mean food chain length. Such increases
      are typically associated with enhanced robustness to secondary extinctions and
      productivity, respectively. Despite these apparent beneficial effects, we find a
      simplification of web structure in terms of taxon richness and diversity, and
      altered proportions of basal and top species. These effects are driven by a
      reduction in community assembly and lower consistency in a range of system
      properties as a result of the multiple stressors. Consequently, impacted food
      webs are likely to be more vulnerable to human- or climate-induced perturbations
      in the long-term.

PMID- 22624199
TI  - Climate heterogeneity modulates impact of warming on tropical insects.
AB  - Evolutionary history and physiology mediate species responses to climate change.
      Tropical species that do not naturally experience high temperature variability
      have a narrow thermal tolerance compared to similar taxa at temperate latitudes
      and could therefore be most vulnerable to warming. However, the thermal
      adaptation of a species may also be influenced by spatial temperature variations
      over its geographical range. Spatial climate gradients, especially from
      topography, may also broaden thermal tolerance and therefore act to buffer
      warming impacts. Here we show that for low-seasonality environments, high spatial
      heterogeneity in temperature correlates significantly with greater warming
      tolerance in insects globally. Based on this relationship, we find that climate
      change projections of direct physiological impacts on insect fitness highlight
      the vulnerability of tropical lowland areas to future warming. Thus, in addition
      to seasonality, spatial heterogeneity may play a critical role in thermal
      adaptation and climate change impacts particularly in the tropics.

PMID- 22624200
TI  - Strong self-limitation promotes the persistence of rare species.
AB  - Theory has recognized a combination of niche and neutral processes each
      contributing, with varying importance, to species coexistence. However, long-term
      persistence of rare species has been difficult to produce in trait-based models
      of coexistence that incorporate stochastic dynamics, raising questions about how
      rare species persist despite such variability. Following recent evidence that
      rare species may experience significantly different population dynamics than
      dominant species, we use a plant community model to simulate the effect of
      disproportionately strong negative frequency dependence on the long-term
      persistence of the rare species in a simulated community. This strong self
      limitation produces long persistence times for the rare competitors, which
      otherwise succumb quickly to stochastic extinction. The results suggest that the
      mechanism causing species to be rare in this case is the same mechanism allowing
      those species to persist.

PMID- 22624201
TI  - Soil nutrient supply modulates temperature-induction cues in mast-seeding
      grasses.
AB  - Synchronous and intermittent reproduction in long-lived plants, known as mast
      seeding, is induced by climatic cues, but the mechanism explaining variation in
      masting among neighboring but edaphically segregated species is unknown. Soil
      nutrients can enhance flowering, and thus, populations on nutrient-rich soils may
      require less-favorable growing temperatures to flower. We tested this hypothesis
      by predicting the probability of flowering in response to air temperature for
      five species of alpine Chionochloa grasses in South Island, New Zealand, over 37
      years and relating our predictions to soil N supply (NH4(+) + NO3(-)). Summer air
      temperatures better predicted flowering than spring air temperatures, which were
      correlated with soil N mineralization. Species on N-rich soils required lower
      mean temperatures to induce flowering and/or responded more consistently across a
      gradient of air temperatures, contributing to the higher probability of their
      tillers and tussocks flowering at low summer temperatures. Our results suggest
      that flowering primarily occurs in response to warm summer temperatures, but
      species on N-rich soils require less favorable growing conditions because they
      invest relatively less N in seeds. Thus, predicting masting requires a
      consideration of the interactions among climate, the internal resources of
      plants, and mineral nutrient uptake.

PMID- 22624202
TI  - A dynamic explanation of size-density scaling in carnivores.
AB  - Population abundance is negatively related to body size for many types of
      organisms. Despite the ubiquity of size-density scaling relationships, we lack a
      general understanding of the underlying mechanisms. Although dynamic models
      suggest that it is possible to predict the intercept and slope of the scaling
      relationship from prior observations, this has never been empirically attempted.
      Here we fully parameterize a set of consumer-resource models for mammalian
      carnivores and successfully predict the size-density scaling relationship for
      this group without the use of free parameters. All models produced similar
      predictions, but comparison of nested models indicated that the primary factors
      generating size-density scaling in mammalian carnivores are prey productivity,
      predator-prey size ratios, and consumer area of capture.

PMID- 22624203
TI  - Measuring diversity: the importance of species similarity.
AB  - Realistic measures of biodiversity should reflect not only the relative
      abundances of species, but also the differences between them. We present a
      natural family of diversity measures taking both factors into account. This is
      not just another addition to the already long list of diversity indices. Instead,
      a single formula subsumes many of the most popular indices, including Shannon's,
      Simpson's, species richness, and Rao's quadratic entropy. These popular indices
      can then be used and understood in a unified way, and the relationships between
      them are made plain. The new measures are, moreover, effective numbers, so that
      percentage changes and ratio comparisons of diversity value are meaningful. We
      advocate the use of diversity profiles, which provide a faithful graphical
      representation of the shape of a community; they show how the perceived diversity
      changes as the emphasis shifts from rare to common species. Communities can
      usefully be compared by comparing their diversity profiles. We show by example
      that this is a far more subtle method than any relying on a single statistic.
      Some ecologists view diversity indices with suspicion, questioning whether they
      are biologically meaningful. By dropping the naive assumption that distinct
      species have nothing in common, working with effective numbers, and using
      diversity profiles, we arrive at a system of diversity measurement that should
      lay much of this suspicion to rest.

PMID- 22624204
TI  - Temporal turnover in the composition of tropical tree communities: functional
      determinism and phylogenetic stochasticity.
AB  - The degree to which turnover in biological communities is structured by
      deterministic or stochastic factors and the identities of influential
      deterministic factors are fundamental, yet unresolved, questions in ecology.
      Answers to these questions are particularly important for projecting the fate of
      forests with diverse disturbance histories worldwide. To uncover the processes
      governing turnover we use species-level molecular phylogenies and functional
      trait data sets for two long-term tropical forest plots with contrasting
      disturbance histories: one forest is older-growth, and one was recently
      disturbed. Having both phylogenetic and functional information further allows us
      to parse out the deterministic influences of different ecological filters. With
      the use of null models we find that compositional turnover was random with
      respect to phylogeny on average, but highly nonrandom with respect to measured
      functional traits. Furthermore, as predicted by a deterministic assembly process,
      the older-growth and disturbed forests were characterized by less than and
      greater than expected functional turnover, respectively. These results suggest
      that the abiotic environment, which changes due to succession in the disturbed
      forest, strongly governs the temporal dynamics of disturbed and undisturbed
      tropical forests. Predicting future changes in the composition of disturbed and
      undisturbed forests may therefore be tractable when using a functional-trait
      based approach.

PMID- 22624205
TI  - Experimental manipulation of seed shadows of an Afrotropical tree determines
      drivers of recruitment.
AB  - The loss of animals in tropical forests may alter seed dispersal patterns and
      reduce seedling recruitment of tree species, but direct experimental evidence is
      scarce. We manipulated dispersal patterns of Manilkara mabokeensis, a monkey
      dispersed tree, to assess the extent to which spatial distributions of seeds
      drive seedling recruitment. Based on the natural seed shadow, we created seed
      distributions with seeds deposited under the canopy ("no dispersal"), with
      declining density from the tree ("natural dispersal"), and at uniform densities
      ("good dispersal"). These distributions mimicked dispersal patterns that could
      occur with the extirpation of monkeys, low levels of hunting, and high rates of
      seed dispersal. We monitored seedling emergence and survival for 18 months and
      recorded the number of leaves and damage to leaves. "Good dispersal" increased
      seedling survival by 26%, and "no dispersal" decreased survival by 78%, relative
      to "natural dispersal." Using a mixed-effects survival model, we decoupled the
      distance and density components of the seed shadow: seedling survival depended on
      the seed density, but not on the distance from the tree. Although community
      seedling diversity tended to decrease with longer dispersal distances, we found
      no conclusive evidence that patterns of seed dispersal influence the diversity of
      the seedling community. Local seed dispersal does affect seedling recruitment and
      survival, with better dispersal resulting in higher seedling recruitment; hence
      the loss of dispersal services that comes with the reduction or extirpation of
      seed dispersers will decrease regeneration of some tree species.

PMID- 22624206
TI  - Evaluating the impacts of multiple generalist fungal pathogens on temperate tree
      seedling survival.
AB  - Host-specific mortality driven by natural enemies is a widely discussed mechanism
      for explaining plant diversity. In principle, populations of plant species can be
      regulated by distinct host-specific natural enemies that have weak or nonexistent
      effects on heterospecific competitors, preventing any single species from
      becoming dominant and thus promoting diversity. Two of the first steps in
      exploring the role of natural enemies in diversity regulation are to (1) identify
      potential enemies and (2) evaluate their levels of host specificity by
      determining if interactions between any one host and its enemy have equivalent
      survival impacts on co-occurring host species. We developed a bioinformatics
      framework to evaluate impacts of potential pathogens on seedling survival, for
      both single and multiple infections. Importantly, we consider scenarios not only
      if there are specialist pathogens for each plant, but also when generalist
      pathogens have differential effects on multiple host species, and when co
      infection has species-specific effects. We then applied this analytical framework
      to a field experiment using molecular techniques to detect potential fungal
      pathogens on co-occurring tree seedling hosts. Combinatorial complexity created
      by 160 plant-fungus interactions was reduced to eight combinations that affect
      seedling survival. Potential fungal pathogens had broad host ranges, but seedling
      species were each regulated by different combinations of fungi or by generalist
      fungi that had differential effects on multiple plant species. Soil moisture can
      have the potential to shift the nature of the interactions in some plant-fungal
      combinations from neutral to detrimental. Reassessing the assumption of single
      enemy-single-host interactions broadens the mechanisms through which natural
      enemies can influence plant diversity.

PMID- 22624207
TI  - Drivers of inter-year variability of plant production and decomposers across
      contrasting island ecosystems.
AB  - Despite the likely importance of inter-year dynamics of plant production and
      consumer biota for driving community- and ecosystem-level processes, very few
      studies have explored how and why these dynamics vary across contrasting
      ecosystems. We utilized a well-characterized system of 30 lake islands in the
      boreal forest zone of northern Sweden across which soil fertility and
      productivity vary considerably, with larger islands being more fertile and
      productive than smaller ones. In this system we assessed the inter-year dynamics
      of several measures of plant production and the soil microbial community (primary
      consumers in the decomposer food web) for each of nine years, and soil
      microfaunal groups (secondary and tertiary consumers) for each of six of those
      years. We found that, for measures of plant production and each of the three
      consumer trophic levels, inter-year dynamics were strongly affected by island
      size. Further, many variables were strongly affected by island size (and thus
      bottom-up regulation by soil fertility and resources) in some years, but not in
      other years, most likely due to inter-year variation in climatic conditions. For
      each of the plant and microbial variables for which we had nine years of data, we
      also determined the inter-year coefficient of variation (CV), an inverse measure
      of stability. We found that CVs of some measures of plant productivity were
      greater on large islands, whereas those of other measures were greater on smaller
      islands; CVs of microbial variables were unresponsive to island size. We also
      found that the effects of island size on the temporal dynamics of some variables
      were related to inter-year variability of macroclimatic variables. As such, our
      results show that the inter-year dynamics of both plant productivity and
      decomposer biota across each of three trophic levels, as well as the inter-year
      stability of plant productivity, differ greatly across contrasting ecosystems,
      with potentially important but largely overlooked implications for community and
      ecosystem processes.

PMID- 22624208
TI  - Postdispersal seed predation limits the abundance of a long-lived perennial forb
      (Lithospermum ruderale).
AB  - Loss of seeds to consumers is common in plant communities, but the degree to
      which these losses influence plant abundance or population growth is often
      unclear. This is particularly the case for postdispersal seed predation by
      rodents, as most studies of rodent seed predation have focused on the sources of
      spatiotemporal variation in seed loss but not quantified the population
      consequences of this loss. In previous work we showed that seed predation by deer
      mice (Peromyscus maniculatus) substantially reduced seedling recruitment and
      establishment of Lithospermum ruderale (Boraginaceae), a long-lived perennial
      forb. To shed light on how rodent seed predation and the near-term effects on
      plant recruitment might influence longer-term patterns of L. ruderale population
      growth, we combined experimental results with demographic data in stage-based
      population models. Model outputs revealed that rodent seed predation had a
      significant impact on L. ruderale population growth rate (lambda). With the
      removal of postdispersal seed predation, the projected population growth rates
      increased between 0.06 and 0.12, depending on site (mean deltalambda across sites
      = 0.08). Seed predation shifted the projected stable stage distribution of
      populations from one with a high proportion of young plants to one in which
      larger adult size classes dominate. Elasticities of vital rates also changed,
      with germination and growth of seedlings and young plants becoming more important
      with the removal of seed predation. Simulations varying the magnitude of seed
      predation pressure while holding other vital rates constant showed that seed
      predation could lower lambda even if only 40% of available seeds were consumed.
      These results demonstrate that rodent granivory can be a potent force limiting
      the abundance of a long-lived perennial forb.

PMID- 22624209
TI  - Changes in seed dispersal processes and the potential for between-patch
      connectivity for an arid land daisy.
AB  - Dispersal is a major and critical process in population biology that has been
      particularly challenging to study. Animals can have major roles in seed dispersal
      even in species that do not appear specifically adapted to animal-aided
      dispersal. This can occur by two processes: direct movement of diaspores by
      animals and modification of landscape characteristics by animals in ways that
      greatly influence dispersal. We exploited the production of large, persistent
      dispersal structures (seed heads, henceforth) by Erodiophyllum elderi
      (Asteraceae), a daisy from arid Australia, to further understand secondary
      dispersal. Seed head dispersal on and off animal tracks in eight E. elderi
      patches was monitored for 9.5 months by periodically recording the location of
      marked seed heads. Sites were located inside a reserve that excludes sheep but
      not kangaroos, and in a nearby area with both kangaroos and sheep. The distance
      moved and likelihood of seed head movement was higher in areas with sheep, and
      especially along animal tracks. There was clear evidence that seed heads were
      channeled down animal tracks during large rainfall events. Seed head dispersal
      away from patches occurred to a limited extent via their physical contact with
      sheep and potentially via wind dispersal. Thus, the advantages of this study
      system allowed us to demonstrate the two postulated effects of herbivores on
      dispersal via direct movement of seed heads, and two distinct indirect effects
      through landscape modification by herbivores from the creation of animal tracks
      and the denudation of vegetation.

PMID- 22624210
TI  - Vertebrate herbivory impacts seedling recruitment more than niche partitioning or
      density-dependent mortality.
AB  - In tropical forests, resource-based niches and density-dependent mortality are
      mutually compatible mechanisms that can act simultaneously to limit seedling
      populations. Differences in the strengths of these mechanisms will determine
      their roles in maintaining species coexistence. In the first assessment of these
      mechanisms in a Congo Basin forest, we quantified their relative strengths and
      tested the extent to which density-dependent mortality is driven by the distance
      dependent behavior of seed and seedling predators predicted by the Janzen-Connell
      hypothesis. We conducted a large-scale seed addition experiment for five randomly
      selected tropical tree species, caging a subset of seed addition quadrats against
      vertebrate predators. We then developed models to assess the mechanisms that
      determine seedling emergence (three months after seed addition) and survival (two
      years after seed addition). As predicted, both niche differentiation and density
      dependent mortality limited seedling recruitment, but predation had the strongest
      effects on seedling emergence and survival. Seedling species responded
      differently to naturally occurring environmental variation among sites, including
      variation in light levels and soil characteristics, supporting predictions of
      niche-based theories of tropical tree species coexistence. The addition of higher
      densities of seeds into quadrats initially led to greater seedling emergence, but
      survival to two years decreased with seed density. Seed and seedling predation
      reduced recruitment below levels maintained by density-dependent mortality, an
      indication that predators largely determine the population size of tree
      seedlings. Seedling recruitment was unrelated to the distance to or density of
      conspecific adult trees, suggesting that recruitment patterns are generated by
      generalist vertebrate herbivores rather than the specialized predators predicted
      by the Janzen-Connell hypothesis. If the role of seed and seedling predation in
      limiting seedling recruitment is a general phenomenon, then the relative
      abundances of tree species might largely depend on species-specific adaptations
      to avoid, survive, and recover from damage induced by vertebrate herbivores.
      Likewise, population declines of herbivorous vertebrate species (many of which
      are large and hunted) may trigger shifts in species composition of tropical
      forests.

PMID- 22624211
TI  - There are many ways to be a mutualist: endophytic fungus reduces plant survival
      but increases population growth.
AB  - One of the challenges to quantifying the costs and benefits of symbiosis is that
      symbionts can influence different components of host fitness. To improve
      understanding of the ecology of inherited symbionts, we developed general theory
      for a perennial host-hereditary symbiont interaction, in which symbionts can have
      independent and potentially opposing effects on host regeneration and survival.
      The model showed that negative effects on one component of fitness may be
      outweighed by positive effects on another, leading to a net positive impact of
      symbiosis on population growth. Model predictions depended on the availability of
      suitable patches, which influenced the relative contributions of survival vs.
      regeneration to host fitness. We then used experimental symbiont removal to
      quantify effects of a hereditary, fungal endophyte on a grass host. Endophyte
      presence strongly reduced host survival but increased regeneration. Application
      of the model revealed that negative effects on plant survival were overwhelmed by
      beneficial effects on regeneration, resulting in stable endophyte persistence at
      100% frequency, consistent with field observations. Our work demonstrates the
      utility of a demographic perspective for predicting the dynamics of symbioses and
      supports the hypothesis that symbionts function as mutualists when host and
      symbiont fitness are coupled through vertical transmission.

PMID- 22624212
TI  - Thieves or mutualists? Pulp feeders enhance endozoochore local recruitment.
AB  - The persistence of mutualisms despite the strong incidence of exploiters could be
      explained if exploiters deny one or more services (i.e., cheat) while eventually
      supplying some subtler but critical services. Pulp feeders usually ingest fruit
      reward without dispersing seeds and thus are considered to be mainly cheaters or
      thieves of seed-disperser mutualisms. By consuming the fruit pulp, however, they
      could release seeds from pulp inhibitory effect, enhancing germination and,
      potentially, subsequent seedling emergence, growth, survival, and thus local
      recruitment. We evaluated such a largely neglected hypothesis by considering the
      interaction between Pyrus bourgaeana and its pulp feeders. We experimentally
      showed that pericarp removal had a consistent strong positive effect on seed
      performance (e.g., lower rotting and higher germination percentages) and seedling
      fate (greater emergence, growth, and survival to two years old). Interestingly,
      these relatively large positive effects of depulpation on plant fitness persisted
      for a surprisingly long time. Though seedlings experienced higher mortality under
      fruiting conspecifics, the benefits of depulpation were not overridden by high
      propagule mortality beneath fruiting trees or in adverse microhabitats after two
      years of monitoring. Specifically, the cumulative probability of establishment
      for depulped seeds was 4-25 times higher than for seeds in whole ripe fruits.
      Thus, under some circumstances, pulp feeders can provide essential services to
      endozoochorous plants. Our study contributes to clarifying the apparent paradox
      of plant-frugivore mutualisms that persist in the face of exploitation by pulp
      feeders. Because "thieves" and "mutualists" refer to the extremes of a complex
      continuum, and because organisms displaying concurrent cheating and honest
      behaviors during different host stages are likely prevalent, the persistent
      language of mutualists vs. thieves, cheaters, or exploiters might be misleading.

PMID- 22624213
TI  - Interactions between mangroves and exotic Spartina in an anthropogenically
      disturbed estuary in southern China.
AB  - Cordgrass (Spartina alterniflora) was introduced to China in 1979 from the United
      States for reducing coastal erosion. It grows vigorously in China and has spread
      over much of the Chinese coast, from Leizhou Peninsula to Liaoning, a range of
      more than 19 degrees of latitude. On the southern coast of China, S. alterniflora
      has invaded mangrove-dominated habitats during the last two decades, but little
      is known about interactions between native mangroves and invasive S.
      alterniflora. We studied the distribution and competitive interactions between
      native mangroves and S. alterniflora in the Zhangjiang Estuary at four tidal
      sites along a salinity gradient: oligohaline upstream, mesohaline, polyhaline,
      and euhaline downstream. S. alterniflora occurred at all four sites, and several
      mangrove species occurred at all but the downstream euhaline site. S.
      alterniflora has invaded the estuary widely and has spread to the lower tidal
      margins of mangroves. It has not invaded mangrove areas with a closed canopy but
      has established in the mangrove zone where the canopy was opened by human
      disturbance. Ramets of S. alterniflora transplanted into the understory of
      mangrove stands with closed canopies died within 10 weeks, but 37.5% survived and
      grew well on open mud flats. S. alterniflora had virtually no competitive effect
      on mangrove seedlings planted at the upstream oligohaline site. However, S.
      alterniflora competitively reduced biomass of mangrove seedlings to 33% over a
      period of 14 weeks at the mesohaline and polyhaline sites where human disturbance
      has opened the mangrove canopy. In contrast, S. alterniflora marginally
      facilitated growth and survival of experimental seedlings at the downstream
      euhaline site. In China, mangroves occur along the coastline south of Whenzhou,
      but they have been severely disturbed and removed widely, mainly by mariculture
      activities. Natural vegetation patterns and our experimental results suggest
      that, without intervention, S. alterniflora could gradually replace these
      mangroves in mid-salinity regions of Chinese estuaries.

PMID- 22624214
TI  - The natives are restless, but not often and mostly when disturbed.
AB  - The argument that the threat posed by introduced species is overblown is often
      buttressed by the observation that native species sometimes also become invasive.
      An examination of the literature on plant invasions in the United States shows
      that six times more nonnative species have been termed invasive than native
      species, and that a member of the naturalized nonnative pool is 40 times more
      likely than a native species to be perceived as invasive. In the great majority
      of instances in which a native plant species is seen as invasive, the invasion is
      associated with an anthropogenic disturbance, especially changed fire or
      hydrological regime, livestock grazing, and changes wrought by an introduced
      species. These results suggest that natives are significantly less likely than
      nonnatives to be problematic for local ecosystems.

PMID- 22624215
TI  - Changes in diatom patch-size distribution and degradation in a spatially self
      organized intertidal mudflat ecosystem.
AB  - Self-organized spatial patterns have been proposed as possible indicators for
      regime shifts in ecosystems. Until now, this hypothesis has only been tested in
      drylands. Here, we focus on intertidal mudflats where regular spatial patterns
      develop in early spring from the interaction between diatom growth and
      sedimentation but disappear when benthic herbivore abundance increases in early
      summer, accompanied by a dramatic shift to a bare mudflat. We followed the patch
      size distributions of diatom biofilms during this degradation process. As time
      progressed, we found a temporal change in the spatial configuration occurring
      simultaneously with the loss of the diatom-sediment feedback. This indicates a
      gradual failure in time of the self-organization process that underlies regular
      patterning in this ecosystem. The path to degradation co-occurred with the loss
      of the larger patches in the ecosystem, which resulted in a decrease of the
      truncation in the patch-size distribution. Hence, our study in mudflat ecosystems
      confirms the general hypothesis that spatial patterns can provide important clues
      about the level of degradation. Nevertheless, our study highlights the need for
      thorough study about the type of spatial patterns and the nature of the
      underlying feedbacks before a reliable assessment of ecosystem status can be
      made, as changes in patch-size distribution differed markedly with those observed
      in other ecosystems.

PMID- 22624216
TI  - Benthic-planktonic coupling, regime shifts, and whole-lake primary production in
      shallow lakes.
AB  - Alternative stable states in shallow lakes are typically characterized by
      submerged macrophyte (clear-water state) or phytoplankton (turbid state)
      dominance. However, a clear-water state may occur in eutrophic lakes even when
      macrophytes are absent. To test whether sediment algae could cause a regime shift
      in the absence of macrophytes, we developed a model of benthic (periphyton) and
      planktonic (phytoplankton) primary production using parameters derived from a
      shallow macrophyte-free lake that shifted from a turbid to a clear-water state
      following fish removal (biomanipulation). The model includes a negative feedback
      effect of periphyton on phosphorus (P) release from sediments. This in turn
      induces a positive feedback between phytoplankton production and P release.
      Scenarios incorporating a gradient of external P loading rates revealed that (1)
      periphyton and phytoplankton both contributed substantially to whole-lake
      production over a broad range of external P loading in a clear-water state; (2)
      during the clear-water state, the loss of benthic production was gradually
      replaced by phytoplankton production, leaving whole-lake production largely
      unchanged; (3) the responses of lakes to biomanipulation and increased external P
      loading were both dependent on lake morphometry; and (4) the capacity of
      periphyton to buffer the effects of increased external P loading and maintain a
      clear-water state was highly sensitive to relationships between light
      availability at the sediment surface and the of P release. Our model suggests a
      mechanism for the persistence of alternative states in shallow macrophyte-free
      lakes and demonstrates that regime shifts may trigger profound changes in
      ecosystem structure and function.

PMID- 22624217
TI  - Transient dynamics and the destabilizing effects of prey heterogeneity.
AB  - The presence of prey heterogeneity and weakly interacting prey species is
      frequently viewed as a stabilizer of predator-prey dynamics, countering the
      destabilizing effects of enrichment and reducing the amplitude of population
      cycles. However, prior model explorations have largely focused on long-term,
      dynamic attractors rather than transient dynamics. Recent theoretical work shows
      that the presence of prey that are defended from predation can have strongly
      divergent effects on dynamics depending on time scale: prey heterogeneity can
      counteract the destabilizing effects of enrichment on predator-prey dynamics at
      long time scales but strongly destabilize systems during transient phases by
      creating long periods of low predator/prey abundance and increasing extinction
      probability (an effect that is amplified with increasing enrichment). We tested
      these general predictions using a planktonic system composed of a zooplankton
      predator and multiple algal prey. We first parameterized a model of our system to
      generate predictions and tested these experimentally. Our results qualitatively
      supported several model predictions. During transient phases, presence of
      defended algal prey increased predator extinctions at low and high enrichment
      levels compared to systems with only a single edible prey. This destabilizing
      effect was moderated at higher dilution rates, as predicted by our model. When
      examining dynamics beyond initial oscillations, presence of the defended prey
      increased predator-prey temporal variability at high nutrient enrichment but had
      no effect at low nutrient levels. Our results highlight the importance of
      considering transient dynamics when assessing the role of stabilizing factors on
      the dynamics of food webs.

PMID- 22624218
TI  - A power-efficiency trade-off in resource use alters epidemiological
      relationships.
AB  - Trade-offs play pivotal roles in the ecology and evolution of natural
      populations. However, trade-offs are probably not static, invariant
      relationships. Instead, ecological factors can shift, alter, or reverse the
      relationships underlying trade-offs and create critical genotype x environment (G
      x E) interactions. But which ecological factors alter trade-offs or create G x E
      interactions, and why (mechanistically) do they do this? We tackle these
      questions using resource quality as the central ecological factor and a case
      study of disease in the plankton. We show that clonal genotypes of a zooplankton
      host (Daphnia dentifera) exhibit a "power-efficiency" trade-off in resource use,
      where powerful (fast-feeding) host clones perform well on richer algal resources,
      but more efficient (slow-feeding) clones perform relatively well on poorer
      resources. This resource-based trade-off then influences epidemiological
      relationships due to fundamental connections between resources and fecundity,
      transmission rate (an index of resistance), and replication of a virulent fungal
      parasite (Metschnikowia bicuspidata) within hosts. For instance, using
      experiments and dynamic energy budget models, we show that the power-efficiency
      trade-off overturned a previously detected trade-off between fecundity and
      transmission risk of hosts to this parasite. When poorer resources were eaten,
      transmission risk and fecundity were negatively, not positively, correlated.
      Additionally, poor resource quality changed positive relationships between yield
      of infectious stages (spores) and host fecundity: those fecundity-spore
      relationships with poor food became negative or nonsignificant. Finally, the
      power-efficiency trade-off set up an interaction between host clone and resource
      quality for yield of fungal spores: powerful clones yielded relatively more
      spores on the better resource, while efficient clones yielded relatively more on
      the poorer resource. Thus, the physiological ecology of resource use can offer
      potent, mechanistic insight linking environmental factors to epidemiological
      relationships.

PMID- 22624219
TI  - From metamorphosis to maturity in complex life cycles: equal performance of
      different juvenile life history pathways.
AB  - Performance in one stage of a complex life cycle may affect performance in the
      subsequent stage. Animals that start a new stage at a smaller size than
      conspecifics may either always remain smaller or they may be able to "catch up"
      through plasticity, usually elevated growth rates. We study how size at and date
      of metamorphosis affected subsequent performance in the terrestrial juvenile
      stage and lifetime fitness of spadefoot toads (Pelobates fuscus). We analyzed
      capture-recapture data of > 3000 individuals sampled during nine years with mark
      recapture models to estimate first-year juvenile survival probabilities and age
      specific first-time breeding probabilities of toads, followed by model selection
      to assess whether these probabilities were correlated with size at and date of
      metamorphosis. Males attained maturity after two years, whereas females reached
      maturity 2-4 years after metamorphosis. Age at maturity was weakly correlated
      with metamorphic traits. In both sexes, first-year juvenile survival depended
      positively on date of metamorphosis and, in males, also negatively on size at
      metamorphosis. In males, toads that metamorphosed early at a small size had the
      highest probability to reach maturity. However, because very few toadlets
      metamorphosed early, the vast majority of male metamorphs had a very similar
      probability to reach maturity. A matrix projection model constructed for females
      showed that different juvenile life history pathways resulted in similar lifetime
      fitness. We found that the effects of date of and size at metamorphosis on
      different juvenile traits cancelled each other out such that toads that were
      small or large at metamorphosis had equal performance. Because the costs and
      benefits of juvenile life history pathways may also depend on population
      fluctuations, ample phenotypic variation in life history traits may be
      maintained.

PMID- 22624220
TI  - Despotic, high-impact species and the subcontinental scale control of avian
      assemblage structure.
AB  - Some species have disproportionate influence on assemblage structure, given their
      numbers or biomass. Most examples of such "strong interactors" come from small
      scale experiments or from observations of the effects of invasive species. There
      is evidence that entire avian assemblages in open woodlands can be influenced
      strongly by individual species over very large areas in eastern Australia, with
      small-bodied species (< 50 g) being adversely affected. We used data from
      repeated surveys in 371 sites in seven districts across a region from Victoria to
      Queensland (> 2000 km). A series of linked Bayesian models was used to identify
      large-bodied (> or = 50 g) bird species that were associated with changes in
      occurrence and abundance of small-bodied species. One native species, the Noisy
      Miner (Manorina melanocephala; family Meliphagidae), was objectively identified
      as the sole large-bodied species having similar detrimental effects in all
      districts, depressing occurrence of 57 of 71 small-bodied species. Adverse
      effects on abundances of small-bodied species were profound when the Noisy Miner
      occurred with mean site abundances > or = 1.6 birds/2 ha. The Noisy Miner may be
      the first species to have been shown to influence whole-of-avifauna assemblage
      structure through despotic aggressiveness over subcontinental scales. These
      substantial shifts in occurrence rates and abundances of small-bodied species
      flow on to alter species abundance distributions of entire assemblages over much
      of eastern Australia.

PMID- 22624221
TI  - Cross-validation of species distribution models: removing spatial sorting bias
      and calibration with a null model.
AB  - Species distribution models are usually evaluated with cross-validation. In this
      procedure evaluation statistics are computed from model predictions for sites of
      presence and absence that were not used to train (fit) the model. Using data for
      226 species, from six regions, and two species distribution modeling algorithms
      (Bioclim and MaxEnt), I show that this procedure is highly sensitive to "spatial
      sorting bias": the difference between the geographic distance from testing
      presence to training-presence sites and the geographic distance from testing
      absence (or testing-background) to training-presence sites. I propose the use of
      pairwise distance sampling to remove this bias, and the use of a null model that
      only considers the geographic distance to training sites to calibrate cross
      validation results for remaining bias. Model evaluation results (AUC) were
      strongly inflated: the null model performed better than MaxEnt for 45% and better
      than Bioclim for 67% of the species. Spatial sorting bias and area under the
      receiver-operator curve (AUC) values increased when using partitioned presence
      data and random-absence data instead of independently obtained presence-absence
      testing data from systematic surveys. Pairwise distance sampling removed spatial
      sorting bias, yielding null models with an AUC close to 0.5, such that AUC was
      the same as null model calibrated AUC (cAUC). This adjustment strongly decreased
      AUC values and changed the ranking among species. Cross-validation results for
      different species are only comparable after removal of spatial sorting bias
      and/or calibration with an appropriate null model.

PMID- 22624222
TI  - Find and forming dedicated people.

PMID- 22624224
TI  - Humanities enrich physician training.

PMID- 22624223
TI  - Physicians and Catholic health care: educating doctors for mission fit.

PMID- 22624225
TI  - The 'soft stuff': medicine as art.

PMID- 22624226
TI  - How the arts help this doctor connect.

PMID- 22624227
TI  - Building a pipeline: connect young talent with the ministry.

PMID- 22624228
TI  - Mission integration leaders: a system draws from many streams.

PMID- 22624229
TI  - The Catholic Teaching Hospital: ethics education enhances skills of doctors in
      training.

PMID- 22624230
TI  - Ethics training for medical interns/residents in the Mercy Health System.

PMID- 22624231
TI  - Integrating ethics into the residency model of physician education.

PMID- 22624232
TI  - Strategies in education: breaking down silos, building up teams.

PMID- 22624233
TI  - Chief nursing officers: program teaches new skills to new leaders.

PMID- 22624234
TI  - Can for-profit Catholic health care get the mission right?

PMID- 22624235
TI  - Physicians and the Affordable Care Act: much to like.

PMID- 22624237
TI  - Nurturing health care ethicists for the future. Efforts continue.

PMID- 22624236
TI  - Hallmarks for assessing a solid program.

PMID- 22624238
TI  - Strict interpretation helps avoid harshness.

PMID- 22624239
TI  - Doing good isn't good enough. Global Summit connecting CHA members with partners
      will advance all of our efforts.

PMID- 22624240
TI  - Cartilage repair in the knee: part II.

PMID- 22624241
TI  - Science and animal models of marrow stimulation for cartilage repair.
AB  - Microfracture of subchondral bone to enhance cartilage repair is a popular
      surgical technique used in human and animal patients. Clinical results with
      resolution or improvement in pain are promising and last on average for 2 to 3
      years. Animal studies aimed at understanding microfracture indicate that the
      repair tissue continues to remodel toward chondrogenesis for at least a year, but
      longer term results are not available to gain insight into the mechanism of
      microfracture function or failure over time. Subchondral bone sclerosis and
      central lesional osteophyte formation following subchondral bone microfracture
      have been observed in animal models of microfracture, but studies do not provide
      any insight into the etiology of these pathologies. The continued maturation of
      microfracture repair tissue over time supports further investigation of
      microfracture or microfracture-augmented cartilage repair procedures with caution
      for the investigator and clinician to be observant for conditions that lead to
      subchondral bone sclerosis or central osteophyte formation, and what affect these
      boney reactions have on clinical outcome.

PMID- 22624242
TI  - Microfracture and augments.
AB  - Microfracture is in widespread clinical use as an intervention for symptomatic
      cartilage defects. While effective when used with strict indications for the
      treatment of smaller defects in the femoral condyles, the resultant
      fibrocartilaginous repair tissue has shown degradation over time when used in
      larger or patellofemoral defects. This article reviews the indications,
      technique, and results of standard microfracture. It also provides an overview of
      augmentation devices such as biomaterials and growth factors that have the
      potential to enhance the outcomes of microfracture, potentially widening its
      indications to include larger defects and other locations. Augmentation
      techniques discussed include collagen and polymer membranes, chitosan and fibrin
      gels, hyaluronan injections, as well as numerous growth factors.

PMID- 22624243
TI  - ACI and MACI.
AB  - Regenerative procedures aim to recreate a hyaline-like tissue, thus restoring a
      biologically and biomechanically valid articular surface with durable clinical
      results. Autologous chondrocyte implantation (ACI) has been developed two decades
      ago, and both the production of a hyaline-like articular surface and a
      satisfactory clinical outcome have been documented at medium-long follow-up.
      Bioengineering technology further improved this regenerative treatment approach
      to include matrix-assisted ACI (MACI) techniques. These procedures have been
      introduced in the clinical practice one decade ago, showing similar results while
      at the same time overcoming most of the concerns related to the first-generation
      ACI. The use of scaffolds to create a cartilage-like tissue in a three
      dimensional culture system allows for the optimization of the procedure from both
      the biological and surgical point of view. However, despite thousands of treated
      patients and many published studies suggesting good clinical results and
      durability of these procedures, the properties of healthy, normal articular
      cartilage are still unmatched by any available substitute. Both indications and
      results of these substitutes are still controversial. The role of many variables
      that may influence the final outcome still need to be clarified to further
      improve the potential benefits of these biological regenerative procedures.

PMID- 22624244
TI  - Particulated articular cartilage: CAIS and DeNovo NT.
AB  - Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and
      DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for
      focal articular cartilage defects in the knee. These methods involve the
      implantation of particulated articular cartilage from either autograft or
      juvenile allograft donor, respectively. In the laboratory and in animal models,
      both CAIS and DeNovo NT have demonstrated the ability of the transplanted
      cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and
      form a new hyaline-like cartilage tissue matrix that integrates with the
      surrounding host tissue. In clinical practice, the technique for both CAIS and
      DeNovo NT is straightforward, requiring only a single surgery to affect cartilage
      repair. Clinical experience is limited, with short-term studies demonstrating
      both procedures to be safe, feasible, and effective, with improvements in
      subjective patient scores, and with magnetic resonance imaging evidence of good
      defect fill. While these treatment options appear promising, prospective
      randomized controlled studies are necessary to refine the indications and
      contraindications for both CAIS and DeNovo NT.

PMID- 22624245
TI  - Nontraditional modification to articular cartilage.
AB  - Biomechanical imbalance, trauma, and age-related degeneration often result in
      chondral lesions, which may lead to overt osteoarthritis over time. Such
      cartilage pathology is frequently accompanied by persistent pain and loss of
      normal joint function. As a result, patients who suffer from biologically active
      articular cartilage lesions are often unable to function in both high level
      activities and exhibit compromised activities of daily living. The limited
      potential for self-regeneration of hyaline cartilage has led to the emergence of
      new technologies to solve this difficult clinical problem. Treatment of arthritis
      and chondral lesions includes alleviation of pain and return of function through
      pharmacologic intervention and/or attempts at cartilage reparative, restorative
      and reconstructive options.

PMID- 22624246
TI  - Methicillin-resistant Staphylococcus aureus screening in total joint
      arthroplasty: a worthwhile endeavor.
AB  - Infections with methicillin-resistant Staphylococcus aureus (MRSA) are an ever
      growing problem in the community, hospitals, and for orthopedic surgeons in
      particular. A conscious effort must be made to deal with this pathogen prior to
      total joint arthroplasty procedures. The drastic increase in prevalence of
      surgical-site infections (SSIs) after total joint replacement surgery has proved
      to be a major health care burden for both patients and surgeons from both a
      medical and financial standpoint. The development of screening techniques for
      detection of MRSA colonization in patients being admitted to hospitals is
      steadily increasing popularity. Particularly nasal swab rapid polymerase chain
      reaction detection of MRSA allows surgeons to identify patients at high risk for
      postoperative SSI. A variety of treatment regimens for eradication of MRSA
      colonization from the nares of surgical patients have surfaced, such as topical
      mupirocin prior to undergoing surgery. Decolonization of MRSA in patients
      undergoing joint arthroplasty procedures has demonstrated encouraging initial
      results in preventing SSIs and should be a serious focus of the future for
      orthopedic surgeons.

PMID- 22624247
TI  - Rotating platform revision total knee arthroplasty.
AB  - Although revision total knee arthroplasty (TKA) procedures are successful in
      relieving pain and restoring function in failed knees, long-term results are
      inferior to primary procedures. Mobile bearing (MB) revision knees can
      potentially improve functional performance. Clinical results of 44 MB rotating
      platform (RP) revision TKAs demonstrated mean knee injury and osteoarthritis
      outcome score (KOOS) activity of daily living score of 77 2 years
      postoperatively. Clinical results were put into context through wear testing
      which demonstrated improved wear performance compared with fixed bearing (FB)
      revision knees. The RP construct is a good choice for revision TKA because it
      permits the surgeon to align the tray for fixation, not compromise rotation of
      the tibial insert, and reduce transmission of shear stresses to the bone, cement
      and implant interface, which is a known cause of failure.

PMID- 22624248
TI  - Patellar dislocation in the United States: role of sex, age, race, and athletic
      participation.
AB  - Patellar instability has been extensively studied in selected, high-risk cohorts,
      but the epidemiology in the general population remains unclear. A longitudinal,
      prospective epidemiological database was used to determine the incidence and
      demographic risk factors for patellar dislocations presenting to emergency
      departments of the United States. The National Electronic Injury Surveillance
      System was queried for all patellar dislocations presenting to emergency
      departments between 2003 and 2008. Incidence rate ratios (IRRs) were then
      calculated with respect to sex, age, and race. The hypothesis was that patellar
      dislocation is influenced by sex, age, race, and athletic participation. An
      estimated 40,544 patellar dislocations occurred among an at-risk population of
      1,774,210,081 person-years for an incidence rate of 2.29 per 100,000 person-years
      in the United States. When compared with males, females showed no significant
      overall or age-stratified differences in the rates of patellar dislocation (IRR
      0.85, 95% CI 0.71, 1.00; p = 0.08; p > 0.05). Peak incidence of patellar
      dislocation occurred between 15 and 19 years of age (11.19/100,000 person-years).
      When compared with Hispanic race, black and white race were associated with
      significantly higher rates of patellar dislocation (IRR 4.30 [95% CI 1.63, 6.97;
      p = 0.02], IRR 4.02 [95% CI 1.06, 6.98; p = 0.03], respectively). Nearly half
      (51.9%) of all patellar dislocation occurred during athletic activity, with
      basketball (18.2%), soccer (6.9%), and football (6.3%) associated with the
      highest percentage of patellar dislocation during athletics. Age between 15 and
      19 years is associated with higher rates of patellar dislocation. Sex is not a
      significant risk factor for patellar dislocation. Black and white race are a
      significant risk factor for patellar dislocation when compared with Hispanic
      race. Half of all patellar dislocation occurs during athletic activity. This
      study was conducted on the Level of evidence II.

PMID- 22624249
TI  - Single compared to double-bundle PCL reconstruction using allograft tissue.
AB  - This study compares the results of arthroscopic transtibial tunnel single-bundle
      and double-bundle posterior cruciate ligament (PCL) reconstructions using
      allograft tissue in PCL-based multiple ligament injured knees. Ninety consecutive
      PCL reconstructions are evaluated: 45 single-bundle and 45 double-bundle
      reconstructions. All PCL reconstructions were performed using the
      arthroscopically assisted transtibial tunnel PCL reconstruction technique using
      fresh frozen allograft tissue from the same tissue bank. Achilles tendon
      allograft was used for the anterolateral bundle; tibialis anterior allograft was
      used for the posteromedial bundle. The knees were evaluated postoperatively,
      comparing the single-bundle results to the double-bundle results, with KT-1000
      arthrometer (Medmetric Corporation, San Diego, CA) testing, three different knee
      ligament rating scales, and Telos stress radiography (Austin Associates,
      Fallston, MD). Both the single-bundle and the double-bundle PCL reconstruction
      surgical techniques using allograft tissue provide successful results in the PCL
      based multiple ligament injured knee when evaluated with stress radiography,
      arthrometer measurements, and knee ligament rating scales.

PMID- 22624250
TI  - Total knee arthroplasty in patients 40 years and younger.
AB  - Total knee arthroplasty (TKA) is a procedure with excellent clinical results in
      older patients with a primary diagnosis of osteoarthritis. Many younger patients
      undergo unicompartmental or high tibial osteotomy rather than TKA, but are not
      always good candidates for these joint-preserving procedures. The purpose of this
      study was to review the outcomes of patients 40 years of age and under who
      underwent TKA. We identified 33 patients (38 knees) who were 40 years of age or
      less at the time of surgery. These patients had a mean age of 36 years (range, 23
      to 40 years), and were followed for a mean of 49 months (range, 16 to 101
      months). The survival rate in the study cohort was 97%. For the young patient who
      is not a candidate for other types of joint preserving procedures, in the senior
      authors' experience total knee arthroplasties have performed well.

PMID- 22624251
TI  - Determining the isometric point of the knee.
AB  - Posteromedial and posterolateral reconstructions of the knee are frequently
      required in the management of knee dislocations. This study compares the accuracy
      of radiographic reference points to established anatomical landmarks in
      reproducing the isometric points of the posteromedial corner and posterolateral
      corner (PLC) of the knee. Posteromedial and posterolateral surgical approaches
      were made in 20 cadaveric knees. The posteromedial and posterolateral isometric
      points of each femur were determined using the anatomic landmarks and
      radiographic reference points in a randomized order. An Isometer was used to
      measure the displacement, to the nearest millimeter; knees were passed into
      flexion. A two-tailed t-test was used to analyze the data and statistical
      significance was set to p < 0.05. For the isometric point of the PLC, the
      radiographic method resulted in a mean displacement of 1.63 mm as the knee was
      passed from extension into flexion, while the anatomic method had a mean
      displacement of 4.84 mm (p < 0.00018). The mean displacement on the posteromedial
      side using the radiographic method was 2.10 mm as the knee was passed from
      extension into flexion, while the anatomic method resulted in 3.21 mm of
      displacement (p = 0.074).

PMID- 22624252
TI  - Primary malignant melanoma of proximal tibia.
AB  - Primary malignant melanoma (clear cell sarcoma) of bone is a very rare neoplasm.
      Although metastatic melanoma to bone is not uncommon, primary malignant melanoma
      of bone is extremely uncommon. To date, only nine cases have been reported in the
      English literature. In this report, we present a case of primary malignant
      melanoma arising from the medial aspect of the proximal tibia in a 26-year-old
      woman. We treated the patient with above-knee amputation without any chemotherapy
      or radiotherapy. At final follow-up of 18 months, the patient was free of
      disease.

PMID- 22624253
TI  - Deep medial collateral ligament tear during knee arthroscopy.
AB  - We report herein deep medial collateral ligament (MCL) tear of the knee with
      application of valgus stress during arthroscopic partial medial meniscectomy.
      With symptomatic treatment only, the patient went on to heal this injury without
      incident and recovered in an expected fashion from arthroscopic surgery. There is
      no earlier report in the literature of deep MCL tear during knee arthroscopy.
      Awareness of this entity, its consequences, and optimal management are essential
      as arthroscopic partial meniscectomy is the most common surgery performed by
      orthopedic surgeons.

PMID- 22624254
TI  - [Acne therapy with a tetracycline: caution sun!].

PMID- 22624255
TI  - [Time spent in emergency service: with reference to Wezel/Liebold my KV has
      canceled the GOP 01440].

PMID- 22624256
TI  - [Physician couple refutes preconceptions about general medicine: "We enjoyed
      being rural physicians"].

PMID- 22624257
TI  - [Loss of driving license: even on call duty will not help].

PMID- 22624258
TI  - [Eyes, nose, mouth, but no face: how a patient with prosopagnosia sees others
      (interview by Dr. Beate Schumacher)].

PMID- 22624259
TI  - [Why it should be treated: hay fever is not a trivial matter].

PMID- 22624260
TI  - [Specific immunotherapy: from the struggle to tolerance].

PMID- 22624261
TI  - [Diabetes therapy for the elderly: for seniors different goals apply].

PMID- 22624262
TI  - [Autoimmune thyroiditis: sneaking into hypothyroidism].

PMID- 22624263
TI  - [Overtraining is dangerous: when sports become murder].

PMID- 22624264
TI  - [Innovations in therapy of atrial fibrillation].

PMID- 22624265
TI  - [Prophylaxis of stroke and embolisms in atrial fibrillation--what is new in the
      guidelines?].

PMID- 22624266
TI  - [Rhythm---control in atrial fibrillation].

PMID- 22624267
TI  - [Update coronary artery disease: important progresses in acute and chronic
      therapy].

PMID- 22624268
TI  - [Emergency checklist: sudden anal pain].

PMID- 22624269
TI  - [Emergency checklist: acute gout attack].

PMID- 22624270
TI  - [Diabetes mellitus and sexuality (sexual dysfunctions in diabetes mellitus)].

PMID- 22624271
TI  - [Case report: Tibial pain: tumor or something innocent?].

PMID- 22624272
TI  - [Abdominal aortic aneurysm: ultrasound screening can lower mortality in patients
      at risk].

PMID- 22624273
TI  - [Hypertension: improved therapy adherence after switch to a fixed drug
      combinations].

PMID- 22624274
TI  - Acute myocardial infarction--the changing face.

PMID- 22624275
TI  - Diagnosis of acute myocardial infarction.
AB  - Diagnosis of acute myocardial infarction (AMI) has to be made early in the
      emergency triage since maximal mortality occurs within first hour and the
      benefits of all interventions are greater once these are instituted early.
      Diagnosis is easy and based on simple principals of good history, physical
      examination, early and complete 12 lead electrocardiogram and use of
      echocardiography which should be available in the emergency triage area.
      Subsequently biomarkers are also available for documentation and risk
      stratification. The other causes of acute severe chest pain should be kept in
      mind and ruled out. The role of myocardial perfusion imaging for diagnosis of AMI
      is limited. The diagnosis also involves an estimation of the size of infarct,
      duration since onset of the process, any acute complications of AMI and the
      likely vessel involved since these have significant therapeutic implications.

PMID- 22624276
TI  - Pre-hospital thrombolysis.
AB  - Coronary heart disease (CHD) is a major cause of mortality in India. Patients in
      India, who have acute coronary syndromes, have a higher rate of STEMI than do
      patients in developed countries. Since most of these patients are poor, they are
      less likely to get evidence-based treatments, and have a greater 30-day
      mortality. Reduction of delays in access to hospital and provision of affordable
      treatments could reduce this. Treatment regimes for AMI should aim to open the
      artery as soon as possible and as wide as possible. In patients suitable for
      thrombolytic treatment, time is critical and reperfusion should be initiated as
      soon as possible. Some adjunctive therapies are also beneficial, in particular,
      the antiplatelet agent aspirin, which should be given in the prehospital setting
      when a diagnosis of AMI is suspected. Despite availability of good treatment,
      mortality from AMI is showing no further reduction due to the prehospital phase
      and in-hospital delays. Thrombolysis is almost always delivered to patients after
      arriving in hospital, losing valuable time (and hence heart muscle). Newer drugs
      combined with recognition of improved outcomes have prompted attempts to decrease
      the time from symptom onset to treatment delivery via Pre Hospital Thrombolysis
      (PHT). However, PHT is significantly superior to in-hospital thrombolysis (IHT).
      This is especially important in regions where PCI is not available. In the RIKS
      HIA and NRMI, PHT had better outcomes than IHT, but patients who received PPCI
      had lower mortality and re-infarction rates. They concluded that within 2 h of
      symptom onset, patients should receive PHT only if PPCI is not available within 4
      h. In CAPTIM, which compared PPCI and PHT followed by PCI if thrombolysis failed
      and in GRACIA-1 trial, which tested the role of systematic PCI within 24 h of
      thrombolysis, the policy of systematic PCI following thrombolysis yielded better
      results than conservative management. The American Heart Association (AHA) and
      the American College of Cardiology (ACC) favour the use of PHT over PCI, placing
      the emphasis on the time factor rather than on the method of reperfusion.
      However, if PHT cannot be administered, the patient should be treated with PPCI
      within 90 min of first medical contact or therapy within 30 min such that the
      total ischaemic time is 120 min. The National Institute for Clinical Excellence
      supports reperfusion with fibrinolytics, recommending PHT using the newer agents,
      reteplase and tenecteplase, whose bolus application simplifies administration.
      PHT constitutes one of the means to shorten delays before the administration of
      reperfusion therapy. However, it poses several organizational problems that can
      find different answers according to each regional/national system of care. A
      number of barriers exist that limit the actual use of PHT. Thus the system of
      care chosen is likely to have a definite impact on the percentage of STEMI
      patients in whom PHT can be delivered.

PMID- 22624277
TI  - Approach to STEMI and NSTEMI.
AB  - Acute coronary syndrome (ACS) refers to any constellation of clinical symptoms
      that are compatible with acute myocardial ischemia. ACS is divided into ST-
      elevated myocardial infarction (STEMI), non-ST elevated myocardial infarction
      (NSTEMI), and unstable angina (UA). STEMI results from complete and prolonged
      occlusion of an epicardial coronary blood vessel and is defined based on ECG
      criteria..NSTEMI usually results from severe coronary artery narrowing, transient
      occlusion, or microembolization of thrombus and/or atheromatous material. NSTEMI
      is defined by an elevation of cardiac biomarkers in the absence of ST elevation.
      The syndrome is termed UA in the absence of elevated cardiac enzymes. History,
      physical examination, ECG, biochemical markers, ECHO all remain important tools
      to make an appropriate diagnosis The management of ACS should focus on rapid
      diagnosis, risk stratification, and institution of therapies that restore
      coronary blood flow and reduce myocardial ischemia.

PMID- 22624278
TI  - Thrombolysis in the era of intervention.
AB  - Thrombolysis revolutionized the treatment of acute ST - elevation myocardial
      infarction in the latter part of the last century and has been in use for more
      than two decades. Use of thrombolytic therapy is widespread owing to its safety,
      efficacy, ease of use, and affordability. Thrombolytic therapy has several
      limitations, many of which have been overcome with the adoption of percutaneous
      coronary intervention techniques in recent years. Primary percutaneous
      intervention is currently the preferred form of reperfusion therapy in the
      management of ST elevation myocardial infarction. However, thrombolytic therapy
      continues to have a role in many situations even in this era of intervention.

PMID- 22624279
TI  - Recent advances in the management of acute myocardial infarction.
AB  - Recently the reperfusion therapy in the form of Primary Percutaneous Coronary
      intervention (PPCI) has become the gold standard for the treatment of Acute
      Myocardial Infarction. In spite of rapid revascularization either with PPCI or
      thrombolytic therapy, the significant number of patients develops decreased left
      ventricular function leading to heart failure which can increase long-term
      mortality and morbidity. The number of strategies are being evolved and evaluated
      to reduce this post infarct heart failure. They are being developed at the level
      of optimizing the outcomes of PPCI, protection against the reperfusion injury,
      and novel therapies like cardiac repair and regeneration and sonothrombolysis.
      Thrombus aspiration using simple aspiration catheters during PPCI are getting
      established as a useful adjunct tool to reduce distal embolisation and
      consequently improving myocardial salvage. The newer antiplatelet drugs like
      Prasugrel and Ticagrelor may replace the Clopidogrel to reduce ischemic
      complications. The reduction in reperfusion injury using drugs has shown mixed
      results. The newer modalities like cardiac repair and regeneration using stem
      cell therapy looks promising but are yet to be established.

PMID- 22624280
TI  - Guidelines for management of acute myocardial infarction.
AB  - These Guidelines summarize and evaluate all currently available evidence on Acute
      Myocardial Infarction (AMI) with the aim of assisting physicians in selecting the
      best management strategies for a typical patient, suffering from AMI, taking into
      account the impact on outcome, as well as the risk/benefit ratio of particular
      diagnostic or therapeutic means. Rapid diagnosis and early risk stratification of
      patients presenting with AMI are important to identify patients in whom early
      interventions can improve outcome. AMI can be defined from a number of different
      perspectives related to clinical, electrocardiographic (ECG), biochemical, and
      pathological characteristics. Quantitative assessment of risk is useful for
      clinical decision making. For patients with the clinical presentation of AMI
      within 12 h after symptom onset, early mechanical (PCI) or pharmacological
      reperfusion should be performed. Platelet activation and subsequent aggregation
      play a dominant role in the propagation of arterial thrombosis and consequently
      are the key therapeutic targets in the management of AMI. Adjunctive therapy with
      antiplatelets and antithrombotics is essential. A recommendation for routine
      urgent PCI (within 24 h) following successful fibrinolysis seems to be most
      practical option. In India, pharmacoinvasive therapy is the best option.

PMID- 22624281
TI  - Managing complications in acute myocardial infarction.
AB  - Acute myocardial infarction (AMI) due to coronary artery disease is a leading
      cause of death in both the developed and developing countries. The advent of
      coronary care units and early reperfusion therapy (Thrombolytic and Percutaneous
      Coronary Intervention) has substantially decreased in-hospital mortality rates
      and has improved the outcome in survivors of the acute phase of MI. Complications
      of AMI include mechanical, arrhythmic, ischemic, and inflammatory (early
      pericarditis and post-MI syndrome) sequelae, as well as left ventricular mural
      thrombus. In addition to these broad categories, right ventricular (RV)
      infarction and cardiogenic shock are other common complications of AMI. The onset
      of each of these complications usually results in explicit symptoms and physical
      manifestations. Thus, a basic knowledge of the complications that occur in the
      postinfarction period and the clinical syndromes associated with each, will allow
      the physician to evaluate and treat the complication appropriately.

PMID- 22624282
TI  - Future of thrombolytic therapy--an Indian context.
AB  - Acute myocardial infarction has two main treatment modalities in the form of
      direct angioplasty (PAMI) and intravenous thrombolysis. PAMI is statistically
      clearly superior to intravenous thrombolysis. However, as ground reality in
      Indian conditions PAMI remains a distant ideal option for many ST elevation MI
      patients. In order to bridge the gap between IV thrombolysis and PAMI, early/pre
      hospital IV thrombolysis to all and early angiography within 3 to 24 hours is the
      treatment modality, which needs to be exercised in India. Because of the
      encouraging results of pharmaco-invasive treatment in acute and long-term
      morbidity and mortality, it should be the prime treatment of management of ST
      elevation myocardial infarction in India. The future of IV thrombolysis will
      remarkably be based on whether Indian physicians switch to direct Fibrin
      Inhibitors like Tenectaplase and Reteplase and whether every patient of ST
      elevation MI undergoes early angiography or not. If these two changes are
      accepted for treatment of ST elevation MI, remarkably successful and effective
      treatment could be offered in a place like India, which is too vast and too
      diversioned and too socio-economically irrelevant for the ideal treatment of
      PAMI. In conclusion, early/pre-hospital thrombolysis with Tenectaplase/Retelase
      and angiography within 3 to 24 hours is the way to go in future in India.

PMID- 22624283
TI  - Cardiac rehabilitation after myocardial infarction.
AB  - Cardiac rehabilitation/secondary prevention programs are recognized as integral
      to the comprehensive care of patients with coronary heart disease (CHD), and as
      such are recommended as useful and effective (Class I) by the American Heart
      Association and the American College of Cardiology in the treatment of patients
      with CHD. The term cardiac rehabilitation refers to coordinated, multifaceted
      interventions designed to optimize a cardiac patient's physical, psychological,
      and social functioning, in addition to stabilizing, slowing, or even reversing
      the progression of the underlying atherosclerotic processes, thereby reducing
      morbidity and mortality. Cardiac rehabilitation, aims at returning the patient
      back to normal functioning in a safe and effective manner and to enhance the
      psychosocial and vocational state of the patient. The program involves education,
      exercise, risk factor modification and counselling. A meta-analysis based on a
      review of 48 randomized trials that compared outcomes of exercise-based
      rehabilitation with usual medical care, showed a reduction of 20% in total
      mortality and 26% in cardiac mortality rates, with exercise-based rehabilitation
      compared with usual medical care. Risk stratification helps identify patients who
      are at increased risk for exercise-related cardiovascular events and who may
      require more intensive cardiac monitoring in addition to the medical supervision
      provided for all cardiac rehabilitation program participants. During exercise,
      the patients' ECG is continuously monitored through telemetry, which serves to
      optimize the exercise prescription and enhance safety. The safety of cardiac
      rehabilitation exercise programs is well established, and the occurrence of major
      cardiovascular events during supervised exercise is extremely low. As hospital
      stays decrease, cardiac rehabilitation is assuming an increasingly important role
      in secondary prevention. In contrast with its growing importance internationally,
      there are very few cardiac rehabilitation centers in India at the present moment.

PMID- 22624284
TI  - Supervisory control of multiple robots: effects of imperfect automation and
      individual differences.
AB  - OBJECTIVE: A military multitasking environment was simulated to examine the
      effects of an intelligent agent, RoboLeader, on the performance of robotics
      operators. BACKGROUND: The participants' task was to manage a team of ground
      robots with the assistance of RoboLeader, an intelligent agent capable of
      coordinating the robots and changing their routes on the basis of battlefield
      developments. METHOD: In the first experiment, RoboLeader was perfectly reliable;
      in the second experiment, RoboLeader's recommendations were manipulated to be
      either false-alarm prone or miss prone, with a reliability level of either 60% or
      90%. The visual density of the targeting environment was manipulated by the
      presence or absence of friendly soldiers. RESULTS: RoboLeader, when perfectly
      reliable, was helpful in reducing the overall mission times.The type of
      RoboLeader imperfection (false-alarm vs. miss prone) affected operators'
      performance of tasks involving visual scanning (target detection, route editing,
      and situation awareness). There was a consistent effect of visual density
      (clutter of the visual scene) for multiple performance measures. Participants'
      attentional control and video gaming experience affected their overall
      multitasking performance. In both experiments, participants with greater spatial
      ability consistently outperformed their low-spatial-ability counterparts in tasks
      that required effective visual scanning. CONCLUSION: Intelligent agents, such as
      RoboLeader, can benefit the overall human-robot teaming performance. However, the
      effects of type of agent unreliability, tasking requirements, and individual
      differences have complex effects on human-agent interaction. APPLICATION: The
      current results will facilitate the implementation of robots in military settings
      and will provide useful data to designs of systems for multirobot control.

PMID- 22624285
TI  - Predicting maximum acceptable efforts for repetitive tasks: an equation based on
      duty cycle.
AB  - OBJECTIVE: The objective was to develop an equation, for repetitive tasks, that
      uses frequency and/or duty cycle (DC) to predict maximum acceptable efforts (MAE)
      relative to maximum voluntary efforts (MVE). BACKGROUND: Ergonomists must
      determine acceptable physical demands for a wide variety of tasks. Although a
      large database exists in the literature for maximum single-effort strength, far
      fewer repetitive tasks have psychophysical and/or physiological data available to
      guide the prediction of acceptable submaximal, repeated efforts. METHOD: DC
      represents the total effort duration divided by the cycle time. MAEs were
      calculated by dividing average psychophysics-based acceptable loads by
      corresponding single-effort maximum strength using 69 values from studies of the
      upper extremities. The author developed an equation to characterize the
      relationship between MAE and DC. RESULTS: The resulting equation had DC taken to
      the exponent 0.24, and it predicted MAE very well (r2 = 0.87%, root mean square
      [RMS] difference = 7.2% of the maximum strength). At higher DC values, the
      equation also demonstrated good agreement with the published physiological data.
      CONCLUSION: The limited psychophysical database in the literature makes it
      difficult for ergonomists and engineers to recommend acceptable efforts for the
      large variety of repetitive tasks they evaluate. However, the proposed equation
      now allows for a correction of the large strength database to estimate acceptable
      force and torque limits for repetitive occupational tasks. APPLICATION: The
      proposed equation will have wide applications for ergonomic practitioners
      performing evaluations of repetitive tasks.

PMID- 22624286
TI  - Earthquakes on the mind: implications of disasters for human performance.
AB  - OBJECTIVE: The present study explored the impact a natural disaster has on human
      performance. BACKGROUND: Previous research indicates that traffic accidents
      increase after disasters. A plausible explanation for this finding is that
      disasters induce cognitive disruption and this disruption negatively affects
      performance (e.g., driving quality). METHOD: A total of 16 participants (7 men
      and 9 women) performed a sustained-attention-to-response task before and after a
      7.1-magnitude earthquake. Performance (errors of omission, errors of commission,
      and reaction time) was compared before and after the earthquake. RESULTS: Errors
      of omission increased after the earthquake. Changes in errors of commission and
      reaction times were, however, dependent on individual differences in stress
      response to the earthquake. CONCLUSION: The results indicate that natural
      disasters may have a negative impact on performance. APPLICATION: Communities
      need to be aware of the increased risk of accidents following disasters and
      develop countermeasures, including individualized assessment tools.

PMID- 22624287
TI  - Human factors-focused reporting system for improving care quality and safety in
      hospital wards.
AB  - OBJECTIVE: The aim was to develop a reporting system for collecting human factors
      problem reports to establish a database to guide activities for improving health
      care quality and patient safety. BACKGROUND: The current error and incident
      report systems do not provide sufficient and adequate coverage of the factors
      contributing to impaired safety and care quality. They fail to examine the range
      of difficulties that clinical staff encounters in the conduct of daily work.
      METHOD: A voluntary problem-reporting system was developed to be used by hospital
      wards' clinicians and was tested in four wards of two hospitals in Israel. The
      system is based on human factors--formatted problem reports submitted by
      physicians and nurses on difficulties and hazards they confront in their daily
      work. Reports are grouped and evaluated by a team of human factor professionals.
      RESULTS: A total of 359 reports were collected in the wards during 12 weeks, as
      compared with a total of 200 incidents reports that were collected during a
      period of 5 years with the existing obligatory incident reporting system. In
      depth observational studies conducted on the wards confirmed the ability of the
      new system to highlight major human factors problems, differentially identifying
      specific problems in each of the wards studied. Problems reported were directly
      related to general factors affecting care quality and patient safety. CONCLUSION:
      Validation studies confirmed the reliability of the reporting system in
      pinpointing major problems per investigated unit according to its specific
      characteristics. APPLICATION: This type of reporting system could fill an
      important information gap with the potential to be a cost-effective initial
      database source to guide human factors efforts to improve care quality, reduce
      errors, and increase patient safety.

PMID- 22624288
TI  - The Play Experience Scale: development and validation of a measure of play.
AB  - OBJECTIVE: A measure of play experience in video games was developed through
      literature review and two empirical validation studies. BACKGROUND: Despite the
      considerable attention given to games in the behavioral sciences, play experience
      remains empirically underexamined. One reason for this gap is the absence of a
      scale that measures play experience. METHOD: In Study 1, the initial Play
      Experience Scale (PES) was tested through an online validation that featured
      three different games (N = 203). In Study 2, a revised PES was assessed with a
      serious game in the laboratory (N = 77). RESULTS: Through principal component
      analysis of the Study 1 data, the initial 20-item PES was revised, resulting in
      the 16-item PES-16. Study 2 showed the PES-16 to be a robust instrument with the
      same patterns of correlations as in Study 1 via (a) internal consistency
      estimates, (b) correlations with established scales of motivation, (c)
      distributions of PES-16 scores in different game conditions, and (d) examination
      of the average variance extracted of the PES and the Intrinsic Motivation Scale.
      CONCLUSION: We suggest that the PES is appropriate for use in further validation
      studies. Additional examinations of the scale are required to determine its
      applicability to other contexts and its relationship with other constructs.
      APPLICATION: The PES is potentially relevant to human factors undertakings
      involving video games, including basic research into play, games, and learning;
      prototype testing; and exploratory learning studies.

PMID- 22624289
TI  - Can passengers' active head tilt decrease the severity of carsickness? Effect of
      head tilt on severity of motion sickness in a lateral acceleration environment.
AB  - OBJECTIVE: We investigated the effect of the passenger head-tilt strategy on the
      severity of carsickness in lateral acceleration situations in automobiles.
      BACKGROUND: It is well known that the driver is generally less susceptible to
      carsickness than are the passengers. However, it is also known that the driver
      tilts his or her head toward the curve center when negotiating a curve, whereas
      the passenger's head moves in the opposite direction. Therefore, we hypothesized
      that the head-tilt strategy has the effect of reducing the severity of
      carsickness. METHOD: A passenger car was driven on a quasi-oval track with a
      pylon slalom while the participant sat in the navigator seat. The experiment was
      terminated when either the participant felt the initial symptoms of motion
      sickness or the car finished 20 laps. In the natural head-tilt condition, the
      participants were instructed to sit naturally, to relax, and not to oppose the
      lateral acceleration intentionally. In the active head-tilt condition, the
      participants were asked to tilt their heads against the centrifugal acceleration,
      thus imitating the driver's head tilt. RESULTS: The number of laps achieved in
      the active condition was significantly greater than that in the natural
      condition. In addition, the subjective ratings of motion sickness and symptoms in
      the active condition were significantly lower than those in the natural
      condition. CONCLUSION: We suggest that an active head tilt against centrifugal
      acceleration reduces the severity of motion sickness. APPLICATION: Potential
      applications of this study include development of a methodology to reduce
      carsickness.

PMID- 22624290
TI  - The effect of apparent latency on simulator sickness while using a see-through
      helmet-mounted display: reducing apparent latency with predictive compensation.
AB  - OBJECTIVE: The aim of this study was to determine the effect of head movement
      frequency and predictive compensation on (a) latency produced in a monocular see
      through helmet-mounted display (HMD) test bed and (b) simulator sickness
      experienced by users wearing the HMD. BACKGROUND: There is conflicting research
      regarding latency as a significant factor in the onset of simulator sickness.
      Predictive compensation has been shown to mitigate the magnitude of latency, but
      little is known about the extent of its effect on simulator sickness. METHOD: A
      video camera recorded HMD and simulator imagery to accurately measure apparent
      latency produced at three head movement frequencies. Predictive compensation
      strategies were manipulated to measure the difference in apparent latency
      produced by the test bed in various conditions. Similar methodology was employed
      with human participants to measure simulator sickness experienced by users of
      this test bed. RESULTS: In Experiment 1, apparent latency increased significantly
      as head movement frequency increased. Predictive compensation strategies
      significantly reduced apparent latency present in the test bed. In Experiment 2,
      predictive compensation significantly reduced the magnitude of simulator
      sickness. CONCLUSION: Predictive compensation can be effectively implemented to
      reduce apparent latency, resulting in a lower magnitude of simulator sickness.
      APPLICATION: Potential applications include HMD use in which head position is
      tracked and visual imagery is linked to head or body movement, such as in virtual
      and augmented reality systems, and is thus critical to functionality and
      performance.

PMID- 22624291
TI  - Scrolling and driving: how an MP3 player and its aftermarket controller affect
      driving performance and visual behavior.
AB  - OBJECTIVE: The aim of this study was to assess how scrolling through playlists on
      an MP3 player or its aftermarket controller affects driving performance and to
      examine how drivers adapt device use to driving demands. BACKGROUND: Drivers use
      increasingly complex infotainment devices that can undermine driving performance.
      The goal activation hypothesis suggests that drivers might fail to compensate for
      these demands, particularly with long tasks and large search set sizes. METHOD: A
      total of 50 participants searched for songs in playlists of varying lengths using
      either an MP3 player or an aftermarket controller while negotiating road segments
      with traffic and construction in a medium-fidelity driving simulator. RESULTS:
      Searching through long playlists (580 songs) resulted in poor driving performance
      and required more long glances (longer than 2 s) to the device compared with
      other playlist lengths. The aftermarket controller also led to more long glances
      compared with the MP3 player. Drivers did not adequately adapt their behavior to
      roadway demand, as evident in their degraded driving performance. No significant
      performance differences were found between short playlists, the radio-tuning
      task, and the no-task condition. CONCLUSION: Selecting songs from long playlists
      undermined driving performance, and drivers did not sufficiently adapt their use
      of the device to the roadway demands, consistent with the goal activation
      hypothesis. The aftermarket controller degraded rather than enhanced performance.
      APPLICATION: Infotainment systems should support drivers in managing distraction.
      Aftermarket controllers can have the unintended effect of making devices carried
      into the car less compatible with driving.These results can motivate development
      of new interfaces as alternatives to scrolling lists.

PMID- 22624292
TI  - Effectiveness of suspension seats in maintaining performance following military
      high-speed boat transits.
AB  - OBJECTIVE: The aim of this study was to investigate whether suspension seats (SS)
      fitted to rigid inflatable boats (RIB) could help maritime boarding teams
      maintain running performance during the high-risk posttransit phase. BACKGROUND:
      High-speed RIB transits have been reported to cause reductions in the running
      performance of boarding teams posttransit. METHOD: In this experiment, two pairs
      of teams completed a 3-hr transit in either calm or rough seas (calm, 5 vs. 5;
      rough, 6 vs. 6) in an RIB fitted with either fixed (FS) or Suspension seats (SS).
      Exhaustive shuttle run distance was measured pre- and immediately posttransit.
      Transit heart rate and perceived exertion (RPE) were measured and deck and seat
      pan acceleration recorded; the latter were reported as impacts count and peak
      magnitude. RESULTS: Distance run was reduced for the FS teams following both
      transits (calm,-250 m,-20%, p < .07; rough, -398 m, -26%, p < .05), whereas it
      was unchanged for the SS teams. All transit heart rates and RPE indicated light
      exertion levels. Seat pan impacts were similarly reduced during the calm transit
      (FS, -42%; SS, -30%); however, during the rough transit, the SS was more than
      twice as effective (FS, -32%; SS, -71%). Peak impact magnitudes were reduced by
      the SS (calm, -38%; rough, -57%) and amplified by the FS (calm, +3%; rough,
      +28%). CONCLUSION: Suspension seats effectively maintained posttransit running
      performance by reducing magnitude of the vertical shocks imposed on the
      passengers. APPLICATION: High-speed RIB transits followed immediately by high
      intensity activity are intrinsic to contemporary maritime operations; suspension
      seats can maintain post-transit physical performance, thereby enhancing safety
      and operational effectiveness.

PMID- 22624293
TI  - Team task analysis: differentiating between tasks using team relatedness and team
      workflow as metrics of team task interdependence.
AB  - OBJECTIVE: As a constructive replication and extension of Arthur, Edwards, Bell,
      Villado, and Bennett (2005), the objective of the current study was to further
      investigate the efficacy of team relatedness and team workflow ratings (along
      with their composite) as metrics of interdependence. BACKGROUND: Although an
      analysis of task and job interdependence has important implications and uses in
      domains such as job design, selection, and training, the job analysis literature
      has been slow to develop an effective method to identify team-based tasks and
      jobs. METHOD: To achieve the study's objectives, 140 F-16 fighter pilots (35 four
      person teams) rated 34 task and activity statements in terms of their team
      relatedness and team workflow. RESULTS: The results indicated that team
      relatedness and team workflow effectively differentiated between tasks with
      varying levels of interdependency (as identified by instructor pilots who served
      as subject matter experts) within the same job. In addition, teams that
      accurately perceived the level of interdependency performed better on a four-ship
      F-16 flight-training program than those that did not. CONCLUSION: Team
      relatedness and team workflow ratings can effectively differentiate between tasks
      with varying levels of interdependency. APPLICATION: Like traditional individual
      task or job analysis, this information can serve as the basis for specified human
      resource functions and interventions, and as diagnostic indicators as well.

PMID- 22624294
TI  - Sweet potato-based complementary food for infants in low-income countries.
AB  - BACKGROUND: In low-income countries, most infants are given cereal-based
      complementary foods prepared at the household level. Such foods are high in
      phytate, which limits the bioavailability of nutrients, including iron, calcium,
      zinc, and in some cases proteins, which are crucial to the development of
      infants. OBJECTIVE: To compare the levels of macronutrients (protein, fat, and
      carbohydrate), gross energy, and fructose in sweet potato-based (denoted ComFa)
      formulations and enriched Weanimix (dehulled maize-dehulled soybean-groundnut
      blend with fish powder and sugar incorporated). The phytate level was also
      compared. METHODS: A composite flour of sweet potato and soybeans containing fish
      powder was processed by oven toasting as a home-based complementary food. Another
      blend containing skim milk powder was processed by extrusion cooking or roller
      drying as industrial-based prototypes. The macronutrient composition and the
      levels of fructose and phytate were determined in the ComFa formulations and
      enriched Weanimix. RESULTS: The ComFa formulations and the enriched Weanimix met
      the stipulated values in the Codex Alimentarius Commission standard for energy
      (400 kcal/100 g), protein (15 g/100 g), and fat (10 to 25 g/100 g) for
      complementary food, with the exception of the industrial-based ComFa
      formulations, which satisfied 83% of the protein requirement (15 g/100 g). The
      ComFa formulations had a quarter of the phytate level of enriched Weanimix. The
      fructose level in the sweet potato-based complementary foods was more than five
      times that in enriched Weanimix. CONCLUSIONS: The sweet potato-based formulations
      were superior to enriched Weanimix as complementary foods for infants in low
      income countries, based on the fructose (which makes the porridge naturally
      sweet) and phytate levels.

PMID- 22624295
TI  - Indian social safety net programs as platforms for introducing wheat flour
      fortification: a case study of Gujarat, India.
AB  - BACKGROUND: Micronutrient deficiencies exact an enormous health burden on India.
      The release of the National Family Health Survey results--showing the relatively
      wealthy state of Gujarat having deficiency levels exceeding national averages-
      prompted Gujarat officials to introduce fortified wheat flour in their social
      safety net programs (SSNPs). OBJECTIVE: To provide a case study of the
      introduction of fortified wheat flour in Gujarat's Public Distribution System
      (PDS), Integrated Child Development Scheme (ICDS), and Mid-Day Meal (MDM)
      Programme to assess the coverage, costs, impact, and cost-effectiveness of the
      initiative. METHODS: India's 2004/05 National Sample Survey data were used to
      identify beneficiaries of each of Gujarat's three SSNPs and to estimate usual
      intake levels of vitamin A, iron, and zinc. Comparing age- and sex-specific usual
      intakes to Estimated Average Requirements, the proportion of the population with
      inadequate intakes was estimated. Postfortification intake levels and reductions
      in inadequate intake were estimated. The incremental cost of fortifying wheat
      flour and the cost-effectiveness of each program were estimated. RESULTS: When
      each program was assessed independently, the proportion of the population with
      inadequate vitamin A intakes was reduced by 34% and 74% among MDM and ICDS
      beneficiaries, respectively. Both programs effectively eliminated inadequate
      intakes of both iron and zinc. Among PDS beneficiaries, the proportion with
      inadequate iron intakes was reduced by 94%. CONCLUSIONS. Gujarat's substitution
      of fortified wheat flour for wheat grain is dramatically increasing the intake of
      micronutrients among its SSNP beneficiaries. The incremental cost of introducing
      fortification in each of the programs is low, and, according to World Health
      Organization criteria, each program is "highly cost-effective." The introduction
      of similar reforms throughout India would largely eliminate the inadequate iron
      intake among persons participating in any of the three SSNPs and would have a
      significant impact on the global prevalence rate of inadequate iron intake.

PMID- 22624296
TI  - Prevalence and sociodemographic factors of malnutrition among children in
      Malaysia.
AB  - BACKGROUND: For many developing countries undergoing rapid economic growth and
      urbanization, trends in nutritional status indicate a decrease in malnutrition
      with an associated rise in the prevalence of obesity. An understanding of the
      situation among children in Malaysia is lacking. OBJECTIVE: To examine the
      prevalence, trends and sociodemographic factors described for underweight and
      overweight children in Malaysia. METHODS: The literature from January 1996 to
      November 2010 on the prevalence of underweight and overweight among children in
      Malaysia was reviewed. RESULTS: Twelve studies were identified that reported on
      both underweight and overweight among children in Malaysia, of which only one was
      a nationally representative survey. Based on the National Health and Morbidity
      Survey in 2006, 13.2% (95% CI, 12.6 to 13.9) of children aged 0 to 18 years were
      underweight (weight-for-age < -2SD), and 8.0% (95% CI, 7.5 to 8.6) of those aged
      0 to 13 years were overweight (weight-for-height > +2SD). Both underweight and
      overweight were more prevalent in males than females. Children in rural areas
      were more likely to be underweight and less likely to be overweight than urban
      children. Ethnic differences between Malays, Chinese, and Indians were
      inconsistent across studies and less clear. Aborigines were more likely to be
      underweight and less likely to be overweight than the general population. The
      available evidence, although limited and sparse, suggests that over the past
      decade the prevalence of both underweight and overweight among children in
      Malaysia has been stable or has shown an increasing trend. CONCLUSIONS: Long-term
      national monitoring and longitudinal cohort studies will be critical for
      understanding, preventing, and managing the double burden of malnutrition among
      children in Malaysia.

PMID- 22624297
TI  - Development, acceptability, and nutritional characteristics of a low-cost, shelf
      stable supplementary food product for vulnerable groups in Kenya.
AB  - BACKGROUND: Food-based approaches have been advocated as the best strategies to
      curb hunger and malnutrition in developing countries. The use of low-cost,
      locally available, nutritious foods in the development of supplementary foods has
      been recommended. OBJECTIVE: To develop low-cost food supplements using different
      traditionally processed local foods, consisting of cereals, legumes, nuts, fish,
      and vegetables, to meet the nutrient requirements for vulnerable groups in Kenya.
      METHODS: Four food supplements were developed and evaluated by taste panel
      procedures. The product containing amaranth grain, pigeon pea, sweet potato,
      groundnuts, and brown sugar was found to be the most acceptable supplement.
      Evaluation of nutritional composition, shelf-life, and cost analysis of the
      acceptable supplement was carried out to assess if it could satisfactorily
      provide more than 50% of the Recommended Dietary Allowances (RDAs) of the basic
      nutrients for vulnerable groups. RESULTS: The acceptable supplement contained
      453.2 kcal energy, 12.7 g crude protein, 54.3 g soluble carbohydrates, 20.8 g
      crude fat, and 10.1 g crude fiber per 110 g. The micronutrient contents were 93.0
      mg calcium, 172.4 mg magnesium, 2.7 mg zinc, 5.7 mg iron, 0.8 mg vitamin B1, 0.2
      mg vitamin B2, 7.9 mg niacin, 100 microg folic acid, and 140 microg retinol
      equivalent per 110 g. The supplement also contained 21% total essential amino
      acid in addition to appreciable levels of palmitic, stearic, oleic, linoleic, and
      alpha-linolenic fatty acids. The shelf-life study showed that it could be stored
      in different packaging materials (polythene bags, gunny bags, and kraft paper) at
      26 degrees C without deleterious effects on its chemical composition for up to 4
      months. Cost analysis of the supplement indicated that the product could be
      competitively sold at US$0.812/kg (KES 65.50/kg). CONCLUSIONS: Locally available
      indigenous foods can be used in the formulation of acceptable, low-cost, shelf
      stable, nutritious supplementary foods for vulnerable groups.

PMID- 22624298
TI  - Response of urinary biomarkers of systemic oxidation to oral iron supplementation
      in healthy men.
AB  - BACKGROUND: Urinary biomarkers are used in assessment of severe, clinical
      oxidative stress. Little is known, however, about their diagnostic value within
      the normative range. OBJECTIVE: To evaluate the response of urinary
      thiobarbituric acid reactive substances (TBARS) and 8-hydroxy-2-deoxyguanosine (8
      OHdG) as indicators of systemic oxidation in response to short-term oral iron and
      antioxidant supplementation. METHODS: Five healthy adult men participated in the
      pilot study phase and 12 in the definitive intervention trial. For 7 days each,
      separated by 12-day washouts, the subjects received different treatment regimens,
      consisting of 120 mg of iron, 120 mg of iron in refined palm oil, and 120 mg of
      iron in palm oil combined with one of the two doses of Carotino Tocotrienol
      Carotene Mixed Concentrate (CTCMC). Creatinine-normalized urinary TBARS and 8
      OHdG concentrations were quantified in samples taken from subjects with and
      without active supplementation. Temporal and correlative associations between
      TBARS and 8-OHdG were explored. RESULTS: Daily intake of supplemental iron failed
      to produce any increment in urinary excretion of TBARS or 8-OHdG. However, a
      significant within-individual correlation between the urinary biomarkers was
      observed (Spearman r = 0.697, p < .0001, n = 466). Both doses of CTCMC
      significantly lowered urinary excretion of both oxidation indicators.
      CONCLUSIONS: Despite the lack of effect of oral iron on the biomarkers of
      systemic oxidation, they show a strong and significant mutual association within
      the nonpathological range of oxidative stress in healthy male adults.

PMID- 22624299
TI  - Comparative intake of white- versus orange-colored maize by Zambian children in
      the context of promotion of biofortified maize.
AB  - BACKGROUND: Vitamin A deficiency is associated with poor health outcomes related
      to reproduction, growth, vision, and immunity. Biofortification of staple crops
      is a novel strategy for combating vitamin A deficiency in high-risk populations
      where staple food intakes are high. African populations are proposed
      beneficiaries of maize (Zea mays) biofortified with provitamin A carotenoids,
      often called "orange maize" because of its distinctive deep yellow-orange
      kernels. The color facilitates ready recognition but presents a cultural
      challenge to maize-consuming populations, including those in much of Africa, who
      traditionally eat white varieties. OBJECTIVE: This study explores the intake
      patterns of, as well as adaptation to, traditional foods made with provitamin A
      biofortified maize compared with white maize in rural Zambian children 3 to 5
      years of age (n = 189) during a 3-month feeding trial. METHODS: The subjects were
      fed a breakfast of maize porridge (sweet mush), a lunch of maize nshima (stiff
      mush) with various side dishes, and an afternoon snack based on a 6-day rotating
      menu. The trial was conducted in 2010. The orange maize used in the trial came
      from three different sources. O1 maize was from the 2009 harvest and was stored
      in a freezer until use in 2010. O2 maize was also from the 2009 harvest and was
      stored in a cold room until 2010. O3 ("fresh") maize was from the 2010 harvest
      and was fed immediately after harvest in week 9 of the study and then stored in a
      freezer until milling for the final four weeks. RESULTS: Consumption of menu
      items, except snacks, was influenced by week (p < .0084). The intakes of porridge
      and nshima made with orange maize equaled those of porridge and nshima made with
      white maize from week 2 onward. The intakes of porridge and nshima prepared from
      O1 and O2 did not differ, but intakes became significantly higher when meals made
      from O3 were introduced (p < .014 for porridge and p < or = .013 for nshima).
      CONCLUSIONS: These results demonstrate quick adaptation to orange maize, a
      preference for recently harvested maize, and an optimistic outlook for similar
      adaptation patterns in other biofortified-maize target countries.

PMID- 22624300
TI  - "Agriculture and malnutrition in India" by Gulati et al.

PMID- 22624301
TI  - Agriculture and malnutrition in India.
AB  - BACKGROUND: Despite the high and relatively stable overall growth of the economy,
      India's agriculture sector is underperforming and a vast section of the
      population remains undernourished. OBJECTIVE: To explore the possible interplay
      between agricultural performance and malnutrition indicators to see whether
      states that perform better in agriculture record better nutritional outcomes.
      METHODS: Correlation analysis and a simple linear regression model were used to
      study the relationship between agricultural performance and malnutrition among
      children under 5 years of age and adults from 15 to 49 years of age at 20 major
      states using data from the National Family Health Survey-3 for the year 2005/06
      and the national accounts. RESULTS: Indicators of the level of agricultural
      performance or income have a strong and significant negative relationship with
      indices of undernutrition among adults and children, a result suggesting that
      improvement of agricultural productivity can be a powerful tool to reduce
      undernutrition across the vast majority of the population. In addition to
      agriculture, access to sanitation facilities and women's literacy were also found
      to be strong factors affecting malnutrition. Access to healthcare for women and
      child-care practices, in particular breastfeeding within 1 hour after birth, are
      other important determinants of malnutrition among adults and children.
      CONCLUSIONS: Malnutrition is a multidimensional problem that requires
      multisectoral interventions. The findings show that improving agricultural
      performance can have a positive impact on nutritional outcomes. However,
      improvements in agriculture alone cannot be effective in combating malnutrition
      if several other mediating factors are not in place. Interventions to improve
      education, health, sanitation and household infrastructure, and care and feeding
      practices are critical. Innovative strategies that integrate agriculture and
      nutrition programs stand a better chance of combating the malnutrition problem.

PMID- 22624302
TI  - Multi-decadal drought and amplified moisture variability drove rapid forest
      community change in a humid region.
AB  - Climate variability, particularly the frequency of extreme events, is likely to
      increase in the coming decades, with poorly understood consequences for
      terrestrial ecosystems. Hydroclimatic variations of the Medieval Climate Anomaly
      (MCA) provide a setting for studying ecological responses to recent climate
      variability at magnitudes and timescales comparable to expectations of coming
      centuries. We examined forest response to the MCA in the humid western Great
      Lakes region of North America, using proxy records of vegetation, fire, and
      hydroclimate. Multi-decadal moisture variability during the MCA was associated
      with a widespread, episodic decline in Fagus grandifolia (beech) populations.
      Spatial patterns of drought and forest changes were coherent, with beech
      declining only in areas where proxy-climate records indicate that severe MCA
      droughts occurred. The occurrence of widespread, drought-induced ecological
      changes in the Great Lakes region indicates that ecosystems in humid regions are
      vulnerable to rapid changes in drought magnitude and frequency.

PMID- 22624303
TI  - Effects of plant species traits on ecosystem processes: experiments in the
      Patagonian steppe.
AB  - Several experiments have shown that aboveground net primary productivity
      increases with plant species richness. The main mechanism proposed to explain
      this relationship is niche complementarity, which is determined by differences in
      plant traits that affect resource use. We combined field and laboratory
      experiments using the most abundant species of the Patagonian steppe to identify
      which are the traits that determine niche complementarity in this ecosystem. We
      estimated traits that affect carbon, water, microclimate, and nitrogen dynamics.
      The most important traits distinguishing among species, from the standpoint of
      their effects on ecosystem functioning, were potential soil nitrification,
      rooting depth, and soil thermal amplitude. Additionally, we explored the
      relationship between trait diversity and aboveground net primary production
      (ANPP) using a manipulative field experiment. ANPP and the fraction of ANPP
      accounted for by trait diversity increased with number of traits. The effect of
      trait diversity decreased as the number of traits increased. Here, the use of
      traits gave us a mechanistic understanding of niche complementarity in the
      Patagonian steppe.

PMID- 22624304
TI  - Epiphyte metapopulation dynamics are explained by species traits, connectivity,
      and patch dynamics.
AB  - The colonization-extinction dynamics of many species are affected by the dynamics
      of their patches. For increasing our understanding of the metapopulation dynamics
      of sessile species confined to dynamic patches, we fitted a Bayesian incidence
      function model extended for dynamic landscapes to snapshot data on five epiphytic
      lichens among 2083 mapped oaks (dynamic patches). We estimate the age at which
      trees become suitable patches for different species, which defines their niche
      breadth (number of suitable trees). We show that the colonization rates were
      generally low, but increased with increasing connectivity in accordance with
      metapopulation theory. The rates were related to species traits, and we show, for
      the first time, that they are higher for species with wide niches and small
      dispersal propagules than for species with narrow niches or large propagules. We
      also show frequent long-distance dispersal in epiphytes by quantifying the
      relative importance of local dispersal and background deposition of dispersal
      propagules. Local stochastic extinctions from intact trees were negligible in all
      study species, and thus, the extinction rate is set by the rate of patch
      destruction (tree fall). These findings mean that epiphyte metapopulations may
      have slow colonization-extinction dynamics that are explained by connectivity,
      species traits, and patch dynamics.

PMID- 22624305
TI  - Incompletely resolved phylogenetic trees inflate estimates of phylogenetic
      conservatism.
AB  - The tendency for more closely related species to share similar traits and
      ecological strategies can be explained by their longer shared evolutionary
      histories and represents phylogenetic conservatism. How strongly species traits
      co-vary with phylogeny can significantly impact how we analyze cross-species data
      and can influence our interpretation of assembly rules in the rapidly expanding
      field of community phylogenetics. Phylogenetic conservatism is typically
      quantified by analyzing the distribution of species values on the phylogenetic
      tree that connects them. Many phylogenetic approaches, however, assume a
      completely sampled phylogeny: while we have good estimates of deeper phylogenetic
      relationships for many species-rich groups, such as birds and flowering plants,
      we often lack information on more recent interspecific relationships (i.e.,
      within a genus). A common solution has been to represent these relationships as
      polytomies on trees using taxonomy as a guide. Here we show that such trees can
      dramatically inflate estimates of phylogenetic conservatism quantified using S.
      P. Blomberg et al.'s K statistic. Using simulations, we show that even randomly
      generated traits can appear to be phylogenetically conserved on poorly resolved
      trees. We provide a simple rarefaction-based solution that can reliably retrieve
      unbiased estimates of K, and we illustrate our method using data on first
      flowering times from Thoreau's woods (Concord, Massachusetts, USA).

PMID- 22624306
TI  - Testing hypotheses in evolutionary ecology with imperfect detection: capture
      recapture structural equation modeling.
AB  - Studying evolutionary mechanisms in natural populations often requires testing
      multifactorial scenarios of causality involving direct and indirect relationships
      among individual and environmental variables. It is also essential to account for
      the imperfect detection of individuals to provide unbiased demographic parameter
      estimates. To cope with these issues, we developed a new approach combining
      structural equation models with capture-recapture models (CR-SEM) that allows the
      investigation of competing hypotheses about individual and environmental
      variability observed in demographic parameters. We employ Markov chain Monte
      Carlo sampling in a Bayesian framework to (1) estimate model parameters, (2)
      implement a model selection procedure to evaluate competing hypotheses about
      causal mechanisms, and (3) assess the fit of models to data using posterior
      predictive checks. We illustrate the value of our approach using two case studies
      on wild bird populations. We first show that CR-SEM can be useful to quantify the
      action of selection on a set of phenotypic traits with an analysis of selection
      gradients on morphological traits in Common Blackbirds (Turdus merula). In a
      second case study on Blue Tits (Cyanistes caeruleus), we illustrate the use of CR
      SEM to study evolutionary trade-offs in the wild, while accounting for varying
      environmental conditions.

PMID- 22624307
TI  - Fitting complex population models by combining particle filters with Markov chain
      Monte Carlo.
AB  - We show how a recent framework combining Markov chain Monte Carlo (MCMC) with
      particle filters (PFMCMC) may be used to estimate population state-space models.
      With the purpose of utilizing the strengths of each method, PFMCMC explores
      hidden states by particle filters, while process and observation parameters are
      estimated using an MCMC algorithm. PFMCMC is exemplified by analyzing time series
      data on a red kangaroo (Macropus rufus) population in New South Wales, Australia,
      using MCMC over model parameters based on an adaptive Metropolis-Hastings
      algorithm. We fit three population models to these data; a density-dependent
      logistic diffusion model with environmental variance, an unregulated stochastic
      exponential growth model, and a random-walk model. Bayes factors and posterior
      model probabilities show that there is little support for density dependence and
      that the random-walk model is the most parsimonious model. The particle filter
      Metropolis-Hastings algorithm is a brute-force method that may be used to fit a
      range of complex population models. Implementation is straightforward and less
      involved than standard MCMC for many models, and marginal densities for model
      selection can be obtained with little additional effort. The cost is mainly
      computational, resulting in long running times that may be improved by
      parallelizing the algorithm.

PMID- 22624308
TI  - Robustness of variance and autocorrelation as indicators of critical slowing
      down.
AB  - Ecosystems close to a critical threshold lose resilience, in the sense that
      perturbations can more easily push them into an alternative state. Recently, it
      has been proposed that such loss of resilience may be detected from elevated
      autocorrelation and variance in the fluctuations of the state of an ecosystem due
      to critical slowing down; the underlying generic phenomenon that occurs at
      critical thresholds. Here we explore the robustness of autocorrelation and
      variance as indicators of imminent critical transitions. We show both
      analytically and in simulations that variance may sometimes decrease close to a
      transition. This can happen when environmental factors fluctuate stochastically
      and the ecosystem becomes less sensitive to these factors near the threshold, or
      when critical slowing down reduces the ecosystem's capacity to follow high
      frequency fluctuations in the environment. In addition, when available data is
      limited, variance can be systematically underestimated due to the prevalence of
      low frequencies close to a transition. By contrast, autocorrelation always
      increases toward critical transitions in our analyses. To exemplify this point,
      we provide cases of rising autocorrelation and increasing or decreasing variance
      in time series prior to past climate transitions.

PMID- 22624309
TI  - Can rare positive interactions become common when large carnivores consume
      livestock?
AB  - Livestock populations in protected areas are viewed negatively because of their
      interaction with native ungulates through direct competition for food resources.
      However, livestock and native prey can also interact indirectly through their
      shared predator. Indirect interactions between two prey species occur when one
      prey modifies either the functional or numerical responses of a shared predator.
      This interaction is often manifested as negative effects (apparent competition)
      on one or both prey species through increased predation risk. But indirect
      interactions can also yield positive effects on a focal prey if the shared
      predator modifies its functional response toward increased consumption of an
      abundant and higher-quality alternative prey. Such a phenomenon between two prey
      species is underappreciated and overlooked in nature. Positive indirect effects
      can be expected to occur in livestock-dominated wildlife reserves containing
      large carnivores. We searched for such positive effects in Acacia-Zizhypus
      forests of India's Gir sanctuary where livestock (Bubalus bubalis and Bos
      indicus) and a coexisting native prey (chital deer, Axis axis) are consumed by
      Asiatic lions (Panthera leo persica). Chital vigilance was higher in areas with
      low livestock density than in areas with high livestock density. This positive
      indirect effect occurred because lion predation rates on livestock were twice as
      great where livestock were abundant than where livestock density was low.
      Positive indirect interactions mediated by shared predators may be more common
      than generally thought with rather major consequences for ecological
      understanding and conservation. We encourage further studies to understand
      outcomes of indirect interactions on long-term predator-prey dynamics in
      livestock-dominated protected areas.

PMID- 22624311
TI  - Scale dependence in species turnover reflects variance in species occupancy.
AB  - Patterns of species turnover may reflect the processes driving community dynamics
      across scales. While the majority of studies on species turnover have examined
      pairwise comparison metrics (e.g., the average Jaccard dissimilarity), it has
      been proposed that the species-area relationship (SAR) also offers insight into
      patterns of species turnover because these two patterns may be analytically
      linked. However, these previous links only apply in a special case where turnover
      is scale invariant, and we demonstrate across three different plant communities
      that over 90% of the pairwise turnover values are larger than expected based on
      scale-invariant predictions from the SAR. Furthermore, the degree of scale
      dependence in turnover was negatively related to the degree of variance in the
      occupancy frequency distribution (OFD). These findings suggest that species
      turnover diverges from scale invariance, and as such pairwise turnover and the
      slope of the SAR are not redundant. Furthermore, models developed to explain the
      OFD should be linked with those developed to explain species turnover to achieve
      a more unified understanding of community structure.

PMID- 22624310
TI  - Harvesting creates ecological traps: consequences of invisible mortality risks in
      predator-prey metacommunities.
AB  - Models of two-patch predator-prey metacommunities are used to explore how the
      global predator population changes in response to additional mortality in one of
      the patches. This could describe the dynamics of a predator in an environment
      that includes a refuge area where that predator is protected and a spatially
      distinct ("risky") area where it is harvested. The predator's movement is based
      on its perceived fitness in the two patches, but the risk from the additional
      mortality is potentially undetectable; this often occurs when the mortality is
      from human harvesting or from a novel type of top predator. Increases in
      undetected mortality in the risky area can produce an abrupt collapse of either
      the refuge population or of the entire predator population when the mortality
      rate exceeds a threshold level. This is due to the attraction of the risky patch,
      which has abundant prey due to its high predator mortality. Extinction of the
      refuge predator population does not occur when the refuge patch has a higher
      maximum per capita predator growth rate than the exploited patch because the
      refuge is then more attractive when the predator is rare. The possibility of
      abrupt extinction of one or both patches from high densities in response to a
      small increase in harvest is often associated with alternative states. In such
      cases, large reductions in mortality may be needed to avoid extinction in a
      collapsing predator population, or to reestablish an extinct population. Our
      analysis provides a potential explanation for sudden collapses of harvested
      populations, and it argues for more consideration of adaptive movement in
      designing protected areas.

PMID- 22624312
TI  - Catastrophe and the life span of coral reefs.
AB  - A strong earthquake in the western Caribbean in 2009 had a catastrophic impact on
      uncemented, unconsolidated coral reefs in the central sector of the shelf lagoon
      of the Belizean barrier reef. In a set of 21 reef sites that had been observed
      prior to the earthquake, the benthic assemblages of 10 were eradicated, and one
      was partially damaged, by avalanching of their slopes. Ecological dynamics that
      had played out over the previous 23 years, including the mass mortalities of two
      sequentially dominant coral species and a large increase in the cover of an
      encrusting sponge, were instantaneously rendered moot in the areas of
      catastrophic reef-slope failure. Because these prior dynamics also determined the
      benthic composition and resilience of adjacent sections of reef that remained
      intact, the history of disturbance prior to the earthquake will strongly
      influence decadal-scale recovery in the failed areas. Geological analysis of the
      reef framework yielded a minimum return time of 2000-4000 years for this type of
      high-amplitude event. Anthropogenic degradation of ecosystems must be viewed
      against the backdrop of long-period, natural catastrophes, such as the impact of
      strong earthquakes on uncemented, lagoonal reefs.

PMID- 22624313
TI  - Sea ice microbial production supports Ross Sea benthic communities: influence of
      a small but stable subsidy.
AB  - Diversity in guilds of primary producers enhances temporal stability in provision
      of organic matter to consumers. In the Antarctic ecosystem, where temporal
      variability in phytoplankton production is high, sea ice contains a diatom and
      microbial community (SIMCO) that represents a pool of organic matter that is
      seasonally more consistent, although of relatively small magnitude. The fate of
      organic material produced by SIMCO in Antarctica is largely unknown but may
      represent an important link between sea ice dynamics and secondary production in
      nearshore food webs. We used whole tissue and compound-specific stable isotope
      analysis of consumers to test whether the sea ice microbial community is an
      important source of organic matter supporting nearshore communities in the Ross
      Sea. We found distinct gradients in delta13C and delta15N of SIMCO corresponding
      to differences in inorganic carbon and nitrogen acquisition among sites with
      different sea ice extent and persistence. Mass balance analysis of a suite of
      consumers demonstrated large fluxes of SIMCO into the nearshore food web, ranging
      from 5% to 100% of organic matter supplied to benthic species, and 0-10% of
      organic matter to upper water column or pelagic inhabitants. A delta13C analysis
      of nine fatty acids including two key biomarkers for diatoms, eicosapentaenoic
      acid (EPA, 20:5omega3), and docosahexaenoic acid (DHA, 22:6omega3), confirmed
      these patterns. We observed clear patterns in delta13C of fatty acids that are
      enriched in 13C for species that acquire a large fraction of their nutrition from
      SIMCO. These data demonstrate the key role of SIMCO in ecosystem functioning in
      Antarctica and strong linkages between sea ice extent and nearshore secondary
      productivity. While SIMCO provides a stabilizing subsidy of organic matter,
      changes to sea ice coverage associated with climate change would directly affect
      secondary production and stability of benthic food webs in Antarctica.

PMID- 22624314
TI  - Meta-ecosystem engineering: nutrient fluxes reveal intraspecific and
      interspecific feedbacks in fragmented mussel beds.
AB  - Ecologists still have to elucidate the complex feedback interactions operating
      among biodiversity and ecosystem processes in engineered systems. To address
      this, a field experiment was conducted to mimic natural mussel bed meta
      ecosystems (Mytilus spp.) of the lower St. Lawrence Estuary (Quebec, Canada) and
      partition the effects of their biotic and abiotic properties and spatial
      structure on ecosystem processes and community dynamics of associated macro
      invertebrates. We found positive intraspecific feedbacks between mussels and
      their recruits, and negative interspecific feedbacks between mussels and their
      associated ecosystem. These feedbacks were associated with mussel bed ecosystem
      processes (fluxes of ammonium and oxygen). In addition, we showed that proximity
      between mussel patches increased within-patch nutrient fluxes. Our study revealed
      the potential for meta-ecosystem engineering to drive feedback interactions
      between community and ecosystem functioning in marine fragmented systems. It also
      shows the relevance of meta-ecosystem theories as a conceptual framework to
      elucidate biotic and abiotic processes controlling ecosystem and community
      structure. Such framework could contribute to ecosystem-based management of
      spatially structured systems such as reserve networks and fragmented ecosystems.

PMID- 22624315
TI  - Tidal regime dictates the cascading consumptive and nonconsumptive effects of
      multiple predators on a marsh plant.
AB  - Prey perception of predators can dictate how prey behaviorally balance the need
      to avoid being eaten with the need to consume resources, and this perception and
      consequent behavior can be strongly influenced by physical processes. Physical
      factors, however, can also alter the density and diversity of predators that
      pursue prey. Thus, it remains uncertain to what extent variable risk perception
      and antipredator behavior vs. variation in predator consumption of prey underlie
      prey-resource dynamics and give rise to large-scale patterns in natural systems.
      In an experimental food web where tidal inundation of marsh controls which
      predators access prey, crab and conch (predators) influenced the survivorship and
      antipredator behavior of snails (prey) irrespective of whether tidal inundation
      occurred on a diurnal or mixed semidiurnal schedule. Specifically, cues of either
      predator caused snails to ascend marsh leaves; snail survivorship was reduced
      more by unrestrained crabs than by unrestrained conchs; and snail survivorship
      was lowest with multiple predators than with any single predator despite
      interference. In contrast to these tidally consistent direct consumptive and
      nonconsumptive effects, indirect predator effects differed with tidal regime:
      snail grazing of marsh leaves in the presence of predators increased in the
      diurnal tide but decreased in the mixed semidiurnal tidal schedule, overwhelming
      the differences in snail density that resulted from direct predation. In
      addition, results suggest that snails may increase their foraging to compensate
      for stress-induced metabolic demand in the presence of predator cues. Patterns
      from natural marshes spanning a tidal inundation gradient (from diurnal to mixed
      semidiurnal tides) across 400 km of coastline were consistent with experimental
      results: despite minimal spatial variation in densities of predators, snails,
      abiotic stressors, and marsh productivity, snail grazing on marsh plants
      increased and plant biomass decreased on shorelines exposed to a diurnal tide.
      Because both the field and experimental results can be explained by tidal-induced
      variation in risk perception and snail behavior rather than by changes in snail
      density, this study reinforces the importance of nonconsumptive predator effects
      in complex natural systems and at large spatial scales.

PMID- 22624316
TI  - Interactions among lignin, cellulose, and nitrogen drive litter chemistry-decay
      relationships.
AB  - Litter decay rates often correlate with the initial ratios of lignin:nitrogen (N)
      or lignin:cellulose in litter. However, the chemical and microbial mechanisms
      that give rise to these patterns are still unclear. To identify these mechanisms,
      we studied the decomposition of a model plant system, Arabidopsis thaliana, in
      which plants were manipulated to have low levels of lignin, cellulose, or litter
      N. Nitrogen fertilizer often increases the loss of cellulose, but it suppresses
      the breakdown of lignin in plant litter. To understand the mechanisms driving
      these patterns, we decomposed plants in litterbags for one year in control and N
      fertilized plots in an Alaskan boreal forest. We found that litter N had a
      positive effect on total mass loss because it increased the loss of lignin, N,
      and soluble C. Lignin had a negative effect on rates of total litter mass loss
      due to decreases in the loss of cellulose and hemicellulose. Cellulose had a
      positive effect on lignin loss, supporting the concept of a "priming effect" for
      lignin breakdown. However, the low-cellulose plants also lost more of their
      original cellulose compared to the other plant types, indicating that decomposers
      mined the litter for cellulose despite the presence of lignin. Low-lignin litter
      had higher fungal biomass and N-acetyl glucosaminidase (NAG, a chitinase)
      activity, suggesting that lignin restricted fungal growth and may have influenced
      competitive interactions between decomposers. Nitrogen fertilization increased
      NAG activity in the early stages of decay. In the later stages, N fertilization
      led to increased cellulase activity on the litters and tended to reduce lignin
      losses. The transition over time from competition among decomposers to high
      cellulase activity and suppressed lignin loss under N fertilization suggests
      that, in N-limited systems, N fertilization may alter decomposer community
      structure by favoring a shift toward cellulose- and mineral-N users.

PMID- 22624317
TI  - CO2 enrichment inhibits shoot nitrate assimilation in C3 but not C4 plants and
      slows growth under nitrate in C3 plants.
AB  - The CO2 concentration in Earth's atmosphere may double during this century. Plant
      responses to such an increase depend strongly on their nitrogen status, but the
      reasons have been uncertain. Here, we assessed shoot nitrate assimilation into
      amino acids via the shift in shoot CO2 and O2 fluxes when plants received nitrate
      instead of ammonium as a nitrogen source (deltaAQ). Shoot nitrate assimilation
      became negligible with increasing CO2 in a taxonomically diverse group of eight
      C3 plant species, was relatively insensitive to CO2 in three C4 species, and
      showed an intermediate sensitivity in two C3-C4 intermediate species. We then
      examined the influence of CO2 level and ammonium vs. nitrate nutrition on growth,
      assessed in terms of changes in fresh mass, of several C3 species and a
      Crassulacean acid metabolism (CAM) species. Elevated CO2 (720 micromol CO2/mol of
      all gases present) stimulated growth or had no effect in the five C3 species
      tested when they received ammonium as a nitrogen source but inhibited growth or
      had no effect if they received nitrate. Under nitrate, two C3 species grew faster
      at sub-ambient (approximately 310 micromol/mol) than elevated CO2. A CAM species
      grew faster at ambient than elevated or sub-ambient CO2 under either ammonium or
      nitrate nutrition. This study establishes that CO2 enrichment inhibits shoot
      nitrate assimilation in a wide variety of C3 plants and that this phenomenon can
      have a profound effect on their growth. This indicates that shoot nitrate
      assimilation provides an important contribution to the nitrate assimilation of an
      entire C3 plant. Thus, rising CO2 and its effects on shoot nitrate assimilation
      may influence the distribution of C3 plant species.

PMID- 22624318
TI  - Seed terminal velocity, wind turbulence, and demography drive the spread of an
      invasive tree in an analytical model.
AB  - Little is known about the relative importance of mechanistic drivers of plant
      spread, particularly when long-distance dispersal (LDD) events occur. Most
      methods to date approach LDD phenomenologically, and all mechanistic models, with
      one exception, have been implemented through simulation. Furthermore, the few
      recent mechanistically derived spread models have examined the relative role of
      different dispersal parameters using simulations, and a formal analytical
      approach has not yet been implemented. Here we incorporate an analytical
      mechanistic wind dispersal model (WALD) into a demographic matrix model within an
      analytical integrodifference equation spread model. We carry out analytical
      perturbation analysis on the combined model to determine the relative effects of
      dispersal and demographic traits and wind statistics on the spread of an invasive
      tree. Models are parameterized using data collected in situ and tested using
      independent data on historical spread. Predicted spread rates and direction match
      well the two historical phases of observed spread. Seed terminal velocity has the
      greatest potential influence on spread rate, and three wind properties
      (turbulence coefficient, mean horizontal wind speed, and standard deviation of
      vertical wind speed) are also important. Fecundity has marginal importance for
      spread rate, but juvenile survival and establishment are consistently important.
      This coupled empirical/theoretical framework enables prediction of plant spread
      rate and direction using fundamental dispersal and demographic parameters and
      identifies the traits and environmental conditions that facilitate spread. The
      development of an analytical perturbation analysis for a mechanistic spread model
      will enable multispecies comparative studies to be easily implemented in the
      future.

PMID- 22624319
TI  - Abundance declines of a native forb have nonlinear impacts on grassland invasion
      resistance.
AB  - The effects of declining plant biodiversity on ecosystem processes are well
      studied, with most investigations examining the role of species richness declines
      rather than declines of species abundance. Using grassland mesocosms, we examined
      how the abundance of a native, resident species, Hemizonia congesta (hayfield
      tarweed), affected exotic Centaurea solstitialis (yellow starthistle) invasion.
      We found that progressive H. congesta abundance declines had threshold effects on
      invasion resistance, with initial declines resulting in minor increases in
      invasion and subsequent declines leading to accelerating increases in invader
      performance. Reduced invasion resistance was explained by increased resource
      availability as H. congesta declined. We also found evidence that resident
      abundance might indirectly affect invasion by mediating invader impact on
      resident competitors; C. solstitialis disproportionately reduced H. congesta
      biomass in low-abundance rather than high-abundance populations. H. congesta's
      direct and indirect effects on invasion resistance illustrate that an individual
      species' declining abundance can have accelerating, deleterious effects on
      ecosystem functions of conservation value.

PMID- 22624320
TI  - Factors driving mortality and growth at treeline: a 30-year experiment of 92 000
      conifers.
AB  - Understanding the interplay between environmental factors contributing to
      treeline formation and how these factors influence different life stages remains
      a major research challenge. We used an afforestation experiment including 92 000
      trees to investigate the spatial and temporal dynamics of tree mortality and
      growth at treeline in the Swiss Alps. Seedlings of three high-elevation conifer
      species (Larix decidua, Pinus mugo ssp. uncinata, and Pinus cembra) were
      systematically planted along an altitudinal gradient at and above the current
      treeline (2075 to 2230 m above sea level [a.s.l.]) in 1975 and closely monitored
      during the following 30 years. We used decision-tree models and generalized
      additive models to identify patterns in mortality and growth along gradients in
      elevation, snow duration, wind speed, and solar radiation, and to quantify
      interactions between the different variables. For all three species, snowmelt
      date was always the most important environmental factor influencing mortality,
      and elevation was always the most important factor for growth over the entire
      period studied. Individuals of all species survived at the highest point of the
      afforestation for more than 30 years, although mortality was greater above 2160 m
      a.s.l., 50-100 m above the current treeline. Optimal conditions for height growth
      differed from those for survival in all three species: early snowmelt (ca. day of
      year 125-140 [where day 1 is 1 January]) yielded lowest mortality rates, but
      relatively later snowmelt (ca. day 145-150) yielded highest growth rates.
      Although snowmelt and elevation were important throughout all life stages of the
      trees, the importance of radiation decreased over time and that of wind speed
      increased. Our findings provide experimental evidence that tree survival and
      height growth require different environmental conditions and that even small
      changes in the duration of snow cover, in addition to changes in temperature, can
      strongly impact tree survival and growth patterns at treeline. Further, our
      results show that the relative importance of different environmental variables
      for tree seedlings changes during the juvenile phase as they grow taller.

PMID- 22624321
TI  - Native ecotypic variation and the role of host identity in the spread of an
      invasive herbivore, Cactoblastis cactorum.
AB  - Environmental niche models (ENMs) have gained enormous popularity as tools to
      investigate potential changes in species distributions resulting from climate
      change and species introductions. Despite recognition that species interactions
      can influence the dynamics of invasion spread, most implementations of ENMs focus
      on abiotic factors as the sole predictors of potential range limits. Implicit in
      this approach is the assumption that biotic interactions are relatively
      unimportant, either because of scaling issues, or because fundamental and
      realized niches are equivalent in a species' native range. When species are
      introduced into exotic landscapes, changes in biotic interactions relative to the
      native range can lead to occupation of different regions of niche space and
      apparent shifts in physiological tolerances. We use an escaped biological control
      organism, Cactoblastis cactorum (Berg.), to assess the role of the environmental
      envelope as compared with patterns of host-herbivore associations based on
      collections made in the native range. Because all nonnative populations are
      derived from a single C. cactorum ecotype, we hypothesize that biotic
      interactions associated with this ecotype are driving the species' invasion
      dynamics. Environmental niche models constructed from known native populations
      perform poorly in predicting nonnative distributions of this species, except
      where there is an overlap in niche space. In contrast, genetic isolation in the
      native range is concordant with the observed pattern of host use, and strong host
      association has been noted in nonnative landscapes. Our results support the
      hypothesis that the apparent shift in niche space from the native to the exotic
      ranges results from a shift in biotic interactions, and demonstrate the
      importance of considering biotic interactions in assessing the risk of future
      spread for species whose native range is highly constrained by biotic
      interactions.

PMID- 22624322
TI  - A simple plant mutation abets a predator-diversity cascade.
AB  - Resource consumption often increases with greater consumer biodiversity. This
      could result either from complementarity among consumers or the inclusion of
      particular key species, and it is often difficult to differentiate between these
      two mechanisms. We exploited a simple plant mutation (reduced production of
      surface waxes) to alter foraging within a community of aphid predators, and thus
      perhaps shift the nature of resulting predator diversity effects. We found that
      greater predator species richness dramatically increased prey suppression and
      plant biomass only on mutant, reduced-wax pea plants (Pisum sativum). On pea
      plants from a sister line with wild type, waxier plant surfaces, predator species
      richness did not influence predators' impacts on herbivores or plants. Thus, a
      change in plant surface structure acted to turn on, or off, the cascading effects
      of predator diversity. Greater predator richness encouraged higher densities of
      true predators but did not lead to greater reproduction by a parasitoid, Aphidius
      ervi; fecundity of each natural enemy species was similar for the two plant
      types. Behavioral observations indicated that although A. ervi was less likely to
      forage within species-rich predator communities, low-wax plants mitigated this
      interference by encouraging generally greater A. ervi foraging and thus high
      rates of aphid dislodgement (aphids dropped from plants to escape A. ervi, but
      not the other predators). Thus, only species-rich, low-wax plants simultaneously
      encouraged strong species-specific effects of A. ervi, and strong complementarity
      among the other predator species. In summary, our study provides evidence that
      diversity effects in predator assemblages are sensitive to habitat
      characteristics. Further, we show that a simple plant morphological trait,
      controlled by a single gene mutation, can dramatically alter the cascading
      effects of predator species richness on herbivores and plants.

PMID- 22624323
TI  - Plant secondary chemistry mediates the performance of a nutritional symbiont
      associated with a tree-killing herbivore.
AB  - Many herbivores consume microbial food sources in addition to plant tissues for
      nutrition. Despite the ubiquity of herbivore-microbe feeding associations, few
      studies examine how host plant phenotypes affect microbial symbionts of
      herbivores. We tested the hypothesis that chemical polymorphism in a plant
      population mediates the performance of nutritional microbial symbionts. We
      surveyed the composition of ponderosa pine resin in northern Arizona, USA, for
      variation in six monoterpenes, and we approximated four chemical phenotypes. We
      reared populations of an herbivorous tree-killing beetle (Dendroctonus
      brevicomis) in ponderosa pine host material, controlling for three monoterpene
      compositions representing an alpha-pinene to delta-3-carene gradient. Beetles
      were reared in host material where the dominant monoterpene was alpha-pinene,
      delta-3-carene, or a phenotype that was intermediate between the two. We isolated
      nutritional fungal symbionts (Entomocorticium sp. B) from beetle populations
      reared in each phenotype and performed reciprocal growth experiments in media
      amended to represent four "average" monoterpene compositions. This allowed us to
      test the effects of natal host phenotype, chemical polymorphism, and the
      interaction between natal host phenotype and chemical polymorphism on a
      nutritional symbiont. Three important findings emerged: (1) fungal isolates grew
      25-32% faster when acquired from beetles reared in the intermediate phenotype;
      (2) the mean growth rate of nutritional fungi varied up to 44% depending on which
      monoterpene composition media was amended with; and (3) fungal isolates uniformly
      performed best in the intermediate phenotype regardless of the chemical
      composition of their natal host. The performance of nutritional fungi related to
      both the chemical "history" of their associated herbivore and the chemical
      phenotypes they are exposed to. However, all fungal isolates appeared adapted to
      a common chemical phenotype. These experiments argue in favor of the hypothesis
      that chemical polymorphism in plant populations mediates growth of nutritional
      symbionts of herbivores. Intraspecific chemical polymorphism in plants
      contributes indirectly to the regulation of herbivore populations, and our
      experiments demonstrate that the ecological effects of plant secondary chemistry
      extend beyond the trophic scale of the herbivore-plant interaction.

PMID- 22624324
TI  - Advertising to the enemy: enhanced floral fragrance increases beetle attraction
      and reduces plant reproduction.
AB  - Many organisms face challenges in avoiding predation while searching for mates.
      For plants, emitting floral fragrances to advertise reproductive structures could
      increase the attraction of detrimental insects along with pollinators. Very few
      studies have experimentally evaluated the costs and benefits of fragrance
      emission with explicit consideration of how plant fitness is affected by both
      pollinators and florivores. To determine the reproductive consequences of
      increasing the apparency of reproductive parts, we manipulated fragrance,
      pollination, and florivores in the wild Texas gourd, Cucurbita pepo var. texana.
      With enhanced fragrance we found an increase in the attraction of florivores,
      rather than pollinators, and a decrease in seed production. This study is the
      first to demonstrate that enhanced floral fragrance can increase the attraction
      of detrimental florivores and decrease plant reproduction, suggesting that
      florivory as well as pollination has shaped the evolution of floral scent.

PMID- 22624325
TI  - Diterpenoid alkaloids of Aconitum vulparia Rchb.
AB  - From the roots of Aconitum vulparia Rchb., collected in Prum (Germany), a new
      norditerpenoid alkaloid, named alexhumboldtine, has been isolated along with the
      known norditerpenoid alkaloids lappaconitine, anthranoyllycoctonine, lycoctonine,
      puberaconitine, ajacine, and septentriodine. The structure of alexhumboldtine was
      established on the basis of 1H, 13C, DEPT, homonuclear 1H COSY, NOESY, HSQC, and
      HMBC NMR studies. From the aerial parts of the plant another norditerpenoid
      alkaloid, aconorine, has been isolated.

PMID- 22624326
TI  - Synthesis of s-triazine-based thiazolidinones as antimicrobial agents.
AB  - A novel series of thiazolidinone derivatives, namely 4-{4-dimethylamino-6-[4-oxo
      2-phenyl-5-(4-pyridin-2-yl-piperazin-1-ylmethyl)-thiazolidin-3-yl]-[1,3,5]
      triazin-2-yloxy}-1-methyl-1H-quinolin-2-ones, have been synthesized from the key
      intermediate 4-(4-amino-6-dimethylamino-[1,3,5]-triazin-2-yloxy)-1-methyl-1H
      quinolin-2-one (5). Compound 5 was condensed with various aldehydes to give
      Schiff base derivatives, which after cyclization gave thiazolidinones that were
      linked with 1-pyridin-2-yl-piperazine to obtain the target compounds. The newly
      synthesized compounds were evaluated for their antimicrobial activity against
      eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli,
      Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus
      vulgaris, Shigella flexneri) and four fungi (Aspergillus niger, Candida albicans,
      Aspergillus fumigatus, Aspergillus clavatus).

PMID- 22624327
TI  - Biological activity of novel N-substituted amides of endo-3-(3-methylthio-1,2,4
      triazol-5-yl)bicyclo[2.2.1]hept-5-ene-2-carboxylic acid and N-substituted amides
      of 1-(5-methylthio-1,2,4-triazol-3-yl)cyclohexane-2-carboxylic acids.
AB  - N-Substituted amides of endo-3-(3-methylthio-1,2,4-triazol-5
      yl)bicyclo[2.2.1]hept-5-ene-2-carboxylic acid and 1-(5-methylthio-1,2,4-triazol-3
      yl)cyclohexane-2-carboxylic acid were prepared by the condensation reaction of
      endo-S-methyl-N1-(bicyclo[2.2.1]hept-5-ene-2,3-dicarbonyl)isothiosemicarbazide
      and S-methyl-N1-(cyclohexane-2,3-dicarbonyl)isothiosemicarbazide with primary
      amines. The synthesized compounds were screened for their microbiological and
      pharmacological activities.

PMID- 22624328
TI  - Cytotoxic constituents of Viscum coloratum.
AB  - Phytochemical studies on Viscum coloratum have resulted in the isolation of
      nineteen compounds. The structures of the isolated compounds were identified on
      the basis of 1D, 2D NMR and HR-ESI-Q-TOF-MS. Pachypodol (4) and ombuine (6) were
      characterized in the family Loranthaceae for the first time. 1,7-Bis(4
      hydroxyphenyl)-1,4-heptadien-3-one (8) and 5-hydroxy-3,7,3'-trimethoxyflavone-4'
      O-beta-D-glucoside (13) were two new natural compounds, which exhibited cytotoxic
      activities against four human tumour cell lines (HeLa, SGC-7901, MCF-7, and
      U251).

PMID- 22624329
TI  - Phenolic compounds from the Mongolian medicinal plant Scorzonera radiata.
AB  - Chromatographic separation of a crude extract obtained from aerial parts of the
      Mongolian medicinal plant Scorzonera radiata yielded fifteen natural compounds,
      including two new flavonoids and one new quinic acid congener, as well as four
      flavones and eight quinic acid derivatives, all of which are known natural
      compounds. The structures of the isolated compounds were elucidated on the basis
      of NMR (1H, 13C, COSY, HMBC, ROESY, and TOCSY) and mass spectrometric data. The
      antioxidant activities of the quinic acid derivatives were evaluated by the DPPH
      assay.

PMID- 22624330
TI  - Chemical constituents and biological activities of Senecio aegyptius var.
      discoideus Boiss.
AB  - A new eremophilane sesquiterpene, 1-beta-hydroxy-8-oxoeremophila-7,9-dien-12-oic
      acid (1), in addition to two known flavonol glycosides, rutin (2) and quercetin-3
      O-glucoside-7-O-rutinoside (3), was isolated from the ethyl acetate fraction
      obtained from the aqueous alcoholic extract of the aerial parts of Senecio
      aegyptius var. discoideus Boiss. (family Asteraceae). The chemical structures of
      the isolated compounds were established by 1D and 2D NMR analysis (1H, 13C, COSY,
      HMQC, HMBC), MS and UV data, and through comparison with the literature. The
      ethyl acetate fraction and the isolated rutin showed significant cytotoxic
      activity against colorectal carcinoma (HCT 116) and to less extent against brain
      (U 251) and breast carcinoma (MCF 7). The ethyl acetate fraction showed a
      significant level of activity against Klebsiella pneumoniae, while the total
      extract showed the best antifungal activity against Candida albicans and
      Saccharomyces cerevisiae. DPPH radical scavenging activity of the ethyl acetate
      fraction was significant (96.7%) when compared to ascorbic acid. It also showed
      anti-inflammatory activity but no diuretic effect.

PMID- 22624331
TI  - Spectroscopic identification of new ellagitannins and a trigalloyl
      glucosylkaempferol from an extract of Euphorbia cotinifolia L. with antitumour
      and antioxidant activity.
AB  - From an extract of leaves and small branches of Euphorbia cotinifolia L., 17
      polyphenols were isolated including two new ellagitannins and a trigalloyl
      glucosylkaempferol. Based on extensive spectral data (UV, ESI-MS, 1H NMR, DEPT
      and 1D/2D NMR) and chemical studies, their structures were characterized as 1-O
      galloyl-3,6-hexahydroxydiphenoyl-D-B1,4-glucopyranose (5), 1-O-galloyl-3,6
      valoneoyl-D-B1,4-glucopyranose (6), and kaempferol 3-O-(2",3",6"-tri-O-galloyl)
      beta-D-glucopyranoside (13). Biological evaluation indicated that the 80% aqueous
      methanol extract (AME), chloroform extract (CE), and some pure compounds have
      potent scavenging activity in the DPPH assay with SC50 values lower than that of
      ascorbic acid, especially 5, 7-9, and a mixture of hyperin 6"-gallate (11) and
      isoquercitrin 6"-gallate (12). Moreover, using the 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl-2H-tetrazolium bromide (MTT) cell viability assay, 6 and 8 exhibited
      the highest inhibition of human hepatocellular carcinoma cells (Hep-G2), while
      AME, CE, 5, 7, 9, and the mixture of 11 and 12 were found to be moderate growth
      inhibitors according to their IC50 values. In addition, AME, 5, and 8 exhibited
      significant antiproliferative activity against colon carcinoma cells (HCT-116);
      however, CE and the other examined compounds displayed moderate to low antitumour
      activity against HCT-116 cells.

PMID- 22624332
TI  - Gastroprotective activity of Sterculia striata A. St. Hil. & Naudin (Malvaceae)
      in rodents.
AB  - The Sterculia striata ethanolic extract (Ss-EtOH) inhibited gastric lesions
      induced by ethanol, HCl/ethanol, and ischemia/reperfusion, but not those induced
      by indomethacin, and did not alter the gastric secretion. Ss-EtOH restored the
      catalase activity and content of nonprotein sulfhydryl groups in the stomach of
      mice treated with ethanol. The gastroprotection induced by Ss-EtOH in the ethanol
      induced gastric lesion model was abolished by N(G)-nitroL-arginine methyl ester
      (L-NAME) pretreatment, suggesting the involvement of nitric oxide and antioxidant
      compounds, but not prostaglandins, in this activity. Lupeol obtained from Ss-EtOH
      promoted gastroprotection as well as the extract at the same dose, and it must
      therefore contribute to the observed effects.

PMID- 22624333
TI  - Anti-Helicobacter pylori activity of the methanolic extract of Geum iranicum and
      its main compounds.
AB  - Geum iranicum Khatamsaz, belonging to the Rosaceae family, is an endemic plant of
      Iran. The methanol extract of the roots of this plant showed significant activity
      against one of the clinical isolates of Helicobacter pylori which was resistant
      to metronidazole. The aim of this study was the isolation and evaluation of the
      major compounds of G. iranicum effective against H. pylori. The compounds were
      isolated using various chromatographic methods and identified by spectroscopic
      data (1H and 13C NMR, HMQC, HMBC, EI-MS). An antimicrobial susceptibility test
      was performed employing the disk diffusion method against clinical isolates of H.
      pylori and a micro dilution method against several Gram-positive and Gram
      negative bacteria; additionally the inhibition zone diameters (IZD) and minimum
      inhibitory concentrations (MIC) values were recorded. Nine compounds were
      isolated: two triterpenoids, uvaol and niga-ichigoside F1, three sterols, beta
      sitosterol, beta-sitosteryl acetate, and beta-sitosteryl linoleate, one phenyl
      propanoid, eugenol, one phenolic glycoside, gein, one flavanol, (+)-catechin, and
      sucrose. The aqueous fraction, obtained by partitioning the MeOH extract with
      water and chloroform, was the most effective fraction of the extract against all
      clinical isolates of H. pylori. Further investigation of the isolated compounds
      showed that eugenol was effective against H. pylori but gein, diglycosidic
      eugenol, did not exhibit any activity against H. pylori. The subfraction D4 was
      the effective fraction which contained tannins. It appeared that tannins were
      probably the active compounds responsible for the anti-H. pylori activity of G.
      iranicum. The aqueous fraction showed a moderate inhibitory activity against both
      Gram-positive and Gram-negative bacteria. The MIC values indicated that Gram
      positive bacteria including Staphylococcus aureus, Staphylococcus epidermidis,
      and Bacillus subtilis are more susceptible than Gram-neagative bacteria including
      Escherichia coli and Pseudomonas aeruginosa.

PMID- 22624334
TI  - Physiological responses of two wheat cultivars to soil drought.
AB  - Young plants of the two wheat cultivars Katya and Prelom, differing in their
      reaction to drought in the field, were grown in soil in pots, and their water
      status was assessed as well as the intensity of gas exchange, chlorophyll
      fluorescence, and accumulation of compatible solutes and hydrogen peroxide after
      7 days of dehydration. It was established that cv. Katya displayed markedly
      better tolerance to soil drying in comparison with cv. Prelom. This was partly
      due to the more effective control of water balance, activity of the
      photosynthetic apparatus, and metabolic activity of leaves under stress.
      Consequently, lower amounts of hydrogen peroxide were accumulated and a lower
      membrane injury index was determined.

PMID- 22624335
TI  - Characterization of Erwinia amylovora strains from Bulgaria by pulsed-field gel
      electrophoresis.
AB  - The aim of this study was to characterize genetically Bulgarian Erwinia amylovora
      strains using pulsed-field gel electrophoresis (PFGE) analysis. Fifty E.
      amylovora strains isolated from different hosts, locations, as well as in
      different years were analysed by PFGE after XbaI, SpeI, and XhoI digestion of the
      genomic DNA. The strains were distributed into four groups according to their
      XbaI-generated profile. About 82% of the strains displayed a PFGE profile
      identical to that of type Pt2. Three strains belonged to the Central Europe Pt1
      type. Two new PFGE profiles, not reported so far, were established--one for a
      strain isolated from Malus domestica and another for all Fragaria spp. strains.
      The same grouping of the strains was obtained after analysis of the SpeI
      digestion patterns. On the basis of PFGE profiles, after XbaI and SpeI digestion,
      a genetic differentiation between the strains associated with subfamily Maloideae
      and subfamily Rosoideae was revealed. The presence of more than one PFGE profile
      in the population of E. amylovora in Bulgaria suggests a multiple source of
      inoculum.

PMID- 22624336
TI  - Improvement of amorpha-4,11-diene production by a yeast-conform variant of
      Vitreoscilla hemoglobin.
AB  - Amorpha-4,11-diene is the precursor of the antimalarial compound artemisinin. The
      effect of Vitreoscilla hemoglobin (VHb) and its yeast-conform variant (VHbm) on
      amorpha-4,11-diene production in engineered Saccharomyces cerevisiae was
      investigated. First, the VHb gene was mutated to the yeast-conform variant VHbm
      based on step-by-step extension of a short region of the gene through a series of
      polymerase chain reactions (PCR). The artificial VHbm gene contained codons
      preferred by the yeast translation machinery. Two yeast expression vectors
      containing VHb or VHbm gene were constructed and introduced into the amorpha-4,11
      diene-producing strain S. cerevisiae WK1 to form WK1[VHb] and WK1[VHbm],
      respectively. Western blot and CO-difference spectrum absorbance assay showed
      that VHb and VHbm were successfully expressed. In shake flasks, VHbm expression
      conferred higher cell growth than VHb expression. GC-MS results indicated the
      amorpha-4,11-diene production in WK1[VHbm] and WK1[VHb] was 3- and 2-fold higher
      than that in WK1, respectively. This suggests that VHb might improve the amorpha
      4,11-diene production in engineered S. cerevisiae.

PMID- 22624337
TI  - Analysis of the low-molecular weight protein profile of egg-white and its changes
      during early chicken embryological development.
AB  - Many low-molecular weight (LMW) proteins in egg-white are potentially bioactive,
      but the mass range and number of these are not yet fully characterized. The aim
      of the present study was to map the LMW protein profile in egg-white and provide
      the basis for further understanding of the physiological function of these
      proteins. For this purpose, six time points (days 0, 1, 2, 3, 4, 5 of incubation)
      were selected in an attempt to delineate the LMW proteomic profile in egg-white
      and its changes during early chicken embryological development. Samples were
      pretreated using gel chromatography techniques prior to analysis by matrix
      assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF
      MS). Protein search focused on the mass range m/z 1,000 to 8,000. One hundred and
      fourteen mass signal peaks of LMW proteins ranging from m/z 1,035.88 to 7,112.91
      were detected at all six time points. The observed changes in the LMW protein
      profile during development were highly dynamic. Eighty six novel mass signal
      peaks of LMW proteins were generated during incubation, the origin of which could
      be assigned to the high-molecular weight protein fractions.The list of egg-white
      LMW proteins provided in this paper is by far the most comprehensive and is
      intended to serve as a starting point for the isolation and functional
      characterization of interesting LMW proteins which may play a crucial role in
      early embryo nutrition and immunity.

PMID- 22624338
TI  - Carbocisteine reduces the cytotoxicity of oxaliplatin.
AB  - Hepatic injury induced by oxaliplatin has been reported. Even though agents are
      available that reduce oxaliplatin-induced hepatocyte toxicity, their mode of
      action has remained obscure. In the present study, hepatic L02 cells were
      incubated with different combinations of oxaliplatin and carbocisteine.
      Significantly increased levels of reactive oxygen species (ROS) were found in L02
      cells treated with oxaliplatin. Using 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) as an indicator of
      cell viability and flow cytometry, we found that carbocisteine could reverse
      oxaliplatin-induced apoptosis of L02 cells. Western blot analysis demonstrated
      that oxaliplatin could induce apoptosis of L02 cells by reducing the Bcl-2/Bim
      ratio, stimulating the cytochrome c release, and activating caspase-3. All of
      these effects could be suppressed by carbocisteine. We further found that
      carbocisteine did not affect the anticancer effect of oxaliplatin against HT-29
      cells. This is the first report opening prospects for the clinical use of
      carbocisteine in the pretreatment against liver injury accompanying the
      chemotherapy regimen with oxaliplatin.

PMID- 22624340
TI  - [Vitamin D and health: Lack of evidence is the biggest problem].

PMID- 22624339
TI  - Cyclic adenosine monophosphate (cAMP)-induced histone hyperacetylation
      contributes to its antiproliferative and differentiation-inducing activities.
AB  - Histone acetylation is linked to the control of chromatin remodeling, which is
      involved in cell growth, proliferation, and differentiation. It is not fully
      understood whether cyclic adenosine monophosphate (cAMP), a representative
      differentiation-inducing molecule, is able to modulate histone acetylation as
      part of its anticancer activity. In the present study, we aimed to address this
      issue using cell-permeable cAMP, i.e. dibutyryl cAMP (dbcAMP) and C6 glioma
      cells. As reported previously, under the conditions of our studies, treatment
      with dbcAMP clearly arrested C6 cell proliferation and altered their morphology.
      Its antiproliferative and differentiation-inducing activity in C6 glioma cells
      involved upregulation of p219WAF/CIP), p27(kip1), glial fibrillary acidic protein
      (GFAP), and Cx43, as well as downregulation of vimentin. Furthermore, dbcAMP
      modulated the phosphorylation of ERK and Akt in a time-dependent manner and
      altered the colocalization pattern of phospho-Src and the actin cytoskeleton.
      Interestingly, dbcAMP upregulated the enzyme activity of histone
      acetyltransferase (HAT) and, in parallel, enhanced cellular acetyllysine levels.
      Finally, the hyperacetylation-inducing compound, sodium butyrate (NaB), a histone
      deacetylase (HDAC) inhibitor, displayed similar anticancer activity to dbcAMP.
      Therefore, our data suggest that antiproliferative and differentiation-inducing
      activities of dbcAMP may be generated by its enhanced hyperacetylation function.

PMID- 22624341
TI  - [Guidelines for allergic rhinitis and asthma must reach out. Primary health care
      and the local pharmacies need to cooperate more].

PMID- 22624342
TI  - [HIV testing should be offered generously. Important both for the individual and
      the society].

PMID- 22624343
TI  - [International guidelines for allergic rhinitis have been updated].

PMID- 22624344
TI  - [Adolescents denied HIV testing at adolescent health centers. Lack of knowledge
      and interest according to a study with simulated client study].

PMID- 22624345
TI  - [Traumatic brain injury can cause pituitary deficiency. Suggestions for
      guidelines for assessment of pituitary function].

PMID- 22624346
TI  - [Certain work can cause neck and shoulder problems. SBU presents a new systematic
      literature review].

PMID- 22624347
TI  - [The right to personal ombudsman should be written in the law].

PMID- 22624348
TI  - [The gender perspective failed - again].

PMID- 22624349
TI  - [Medicines for type 2 diabetes: fine tuning rather than redesign].

PMID- 22624350
TI  - [Retigabine. A novel anticonvulsant drug for the adjunctive treatment of partial
      seizures].

PMID- 22624351
TI  - [Fatigue in cancer patients].
AB  - Fatigue is characterized by persistent tiredness or exhaustion and besides the
      anorexia-nausea-emesis syndrome one of the most frequent adverse events of cancer
      treatment. There is a large variety of causes and symptoms. Various non
      pharmacologic and pharmacologic interventions can help to ameliorate the symptoms
      and to improve patient's quality of life. For the effective management of fatigue
      a systematic approach of the multiprofessional team is required. Last but not
      least, the pharmacist can contribute to support cancer patients suffering from
      fatigue.

PMID- 22624352
TI  - [Right heart failure in the ICU. The primary goal of treatment is to reduce right
      ventricular afterload].

PMID- 22624353
TI  - [What is histamine intolerance?].

PMID- 22624354
TI  - [Stable carbon isotope of black carbon from typical emission sources in China].
AB  - Smoke particles from the three typical BC emission sources (biomass burning,
      household coal combustion, and vehicular exhaust) were collected and analyzed for
      stable carbon isotopes (delta13C) of black carbon (BC), total carbon (TC), as
      well as the original fuels. The results show that corn stalk (a typical C4 plant,
      -13.62 per thousand) has the highest delta13C(BC) value, and the average values
      for C3 plants, bituminous coals, and vehicle exhaust are -26.49 per thousand +/-
      1.17 per thousand, -23.46 per thousand +/- 0.37 per thousand, and -25.17 per
      thousand +/- 0.40 per thousand, respectively. delta13C(BC) values from the three
      sources are similar to the corresponding fuels, and the ranges of these values
      are different from each other. Carbon fractionation occurs during the process of
      BC formation. delta13C(BC) for C4 plant (corn stalk) is lower than that of the
      fuel by 1.62 per thousand, while the values for C3 plants and coals are higher
      than that of the fuels by 0.63 per thousand and 0.52 per thousand, respectively.
      CTO-375 method, which is used to extract BC from TC, affects the stable carbon
      isotope of smokes from biomass burning to some extent (the difference between
      delta13C(BC) and delta13C(TC) is nearly 0.50 per thousand), but has little effect
      on fossil fuel smokes. This delta13C database for typical emission sources
      provides scientific information on BC source apportionment.

PMID- 22624355
TI  - [Characteristics of carbonaceous aerosol concentration in snow and ice of
      glaciers in Tianshan Mountains].
AB  - The snow and ice samples, collected at Glacier No. 1 at the headwaters of Urumqi
      River (UG1) and Glacier No. 51 at Haxilegen of Kuytun River (HG51) in 2002 and
      2004, were analyzed for organic carbon (OC) and element carbon (EC) by thermal/
      optical reflectance (TOR). The spatio-temporal characteristics and environmental
      significance of OC and EC concentration were discussed in details. The
      concentration order of total carbon (TC) was: snowpack of west branch on UG1 (1
      943 ng x g(-1)) > snowpack of east branch on UG1 (989 ng x g(-1)) > snowpack of
      HG51 (150 ng x g(-1)) > glacier ice of east branch on UG1 (77 ng x g(-1)), and
      the concentration order of OC and EC lay similar as TC. The concentration of OC
      and EC in snowpack of Tianshan Mountains were 557 ng x g(-1) and 188 ng x g(-1),
      respectively. Concentration peak of carbonaceous aerosol usually appeared near
      the dust layer at the bottom section of snowpack, but the some sudden events
      could increase the concentration in the surface snow. Because of the seasonality
      of carbon emission (e. g. heating and agricultural activities) and transportation
      (e. g. atmospheric circulation), the concentration of carbonaceous aerosol
      increased from July to November with fluctuations. Difference on the order of
      magnitude might exist between the concentration in snow (firn) and glacier ice,
      which was influenced by the glacier surroundings, sampling situation and other
      factors. EC on the surface snow affected the albedo significantly, and an average
      albedo reduction of 0.22 in the wavelength of 300-700 nm was simulated by SNICAR
      (snow, ice, and aerosol radiative) model.

PMID- 22624356
TI  - [Size distribution properties of atmospheric aerosol particles during summer and
      autumn in Lanzhou].
AB  - Atmospheric particle size distributions (size range 0.5-20 microm) were measured
      using aerodynamic particle sizer (APS-3321) from August 1st to October 31st in
      Lanzhou. Variations of particle concentrations and properties of volume
      concentration distributions were analyzed through cluster analysis. The main
      objective of this study was to identify factors affecting the particle size
      distributions in Lanzhou. The hourly averaged particle number, surface area and
      volume concentrations are (108.1 +/- 92.2) cm(-3), (282.9 +/- 267.9) microm2 x
      cm(-3) and (92.2 +/- 127.3) microm3 x cm(-3), respectively. The number, surface
      area and volume concentrations of fine particles (0.5-2.5 microm) account for
      98.7%, 73.8% and 52.9% of the total particle concentrations in 0.5-20 microm,
      respectively. The size distribution of number concentrations is unimodal with a
      peak at accumulation mode. The size distributions of surface area and volume
      concentrations are bimodal with peaks at accumulation mode and coarse mode,
      respectively. The size distributions of particle volume concentrations mainly
      have 7 clusters, indicating the effect of different sources and meteorological
      conditions. Coarse mode particles are dominant in particle volume size
      distributions affected by wind-borne dust and on dust days, while that affected
      by motor vehicle combustion emissions and traffic resuspended dust are
      characterized by bimodal with peaks at accumulation mode and coarse mode,
      respectively.

PMID- 22624357
TI  - [Particle number size distribution near a major road with different traffic
      conditions].
AB  - The profiles of number concentration of ambient particles at a roadside site in
      Beijing were studied with different traffic conditions. A Scanning Mobility
      Particle Sizer (SMPS) was utilized to measure the number concentrations of fine
      and ultrafine (10-100 nm) particles in August 2008 and August 2009, which
      represented the normal and Olympic traffic conditions, respectively. Size
      distributions of particle number concentration were identified and their temporal
      variations were also discussed. Results indicated that with normal traffic
      pattern, the total number concentration of ultrafine and 10-478 nm particles were
      (1.15 +/- 0.49) x 10(4) cm(-3) and (1.61 +/- 0.57) x 10(4) cm(-3), respectively.
      While the concentrations were decreased to (0.55 +/- 0.14) x 10(4) cm(-3) and
      (1.21 +/- 0.24) x 10(4) cm(-3), respectively, with special traffic condition
      during the Beijing Olympic Games. Largest reduction of 52.2% was observed for
      ultrafine particles among all size ranges. With normal traffic condition, bimodal
      distribution was found with two peak values in number concentrations around 22.5
      nm and 113.0 nm. During the Olympic period, nucleation mode particles were
      significantly reduced due to a series of temporal control measures on motor
      vehicles such as the removal of yellow-labeled vehicles from the roads and travel
      restrictions based on odd-even license plate numbers. As a result, the peak in
      particle number concentration at 22.5 nm disappeared. The temporal variation
      indicated that significantly higher ultrafine particle number concentrations
      occurred around 00 : 00-04 : 00, 11 : 00-13 : 00 and 17 : 00-20 : 00 with normal
      traffic situation, which primarily attributed to the contributions of diesel
      exhaust at night, secondary formation at noon and traffic jam in the evening,
      respectively. However during the Olympic period, the temporal variation pattern
      changed significantly. The gap in the number concentrations of ultrafine particle
      between these three time periods and other time periods were narrowed, which
      should be attributed to the reduction of traffic flow as well as the increase of
      fleet speed during the Olympics.

PMID- 22624358
TI  - [Atmospheric particle formation events in Nanjing during summer 2010].
AB  - Feature of aerosol particle number concentration, condition and impact factor of
      new particle formation (NPF) were investigated in Nanjing during summer. In this
      study, aerosol particle number concentration and gaseous pollutants (O3, SO2 and
      NO2) measurements were carried out by Wide-Range Particle Spectrometer (WPS) and
      Differential Optical Absorption Spectroscopy (DOAS) in July 2010. Combining with
      observations from Automatic Weather Station and Backward Trajectory Simulation,
      the condition and impact factor of NPF were discussed. Results showed that the
      averaged 10-500 nm particle number concentration was 1.7 x 10(4) cm(-3), similar
      to some typical observation values in North American and Europe; the 10-25 nm
      particle number concentration accounted for 25% of the total number
      concentration. Six NPF events occurred during observation. We analyzed that
      stable wind speed and direction, strong solar radiation promoted the NPF. The
      humidity during NPF event varied from 50% to 70%. Results indicated that clean
      ocean air mass brought from easterly and southerly wind promoted the NPF by
      Backward Trajectory Model Simulation. During the NPF event, the 10 - 25 nm
      particle number concentration positively correlated with the concentration of
      SO2, and negatively correlated with O3, whereas poorly correlated with NO2.

PMID- 22624359
TI  - [Characteristics of delta18O in precipitation and moisture transports over the
      arid region in Northwest China].
AB  - Based on the observed data of stable isotopes in precipitation and meteorological
      statistics at Urumqi (1986-2003), Zhangye (1986-2003), and Hotan (1988-1992) from
      IAEA/WMO, the precipitation equation of arid region in Northwest China was
      calculated through the regression analysis, and the characteristics of stable
      isotopic in precipitation, as well as the correlation between stable isotopic and
      meteorological records, were analyzed. The water vapor source of the three sites
      was tracked by the HYSPLIT4. 9 model, and water vapour transmission regime of
      arid region in Northwest China was established, while the record of delta18O in
      cryosphere was discussed. Results showed that the precipitation equation of
      deltaD = 7.24 delta18O + 1.96 per thousand indicates intense evaporation;
      delta18O values at Urumqi, Zhangye and Hotan fluctuates at -20.58 per thousand- 
      5.4 per thousand, -18.58 per thousand- -2.46 per thousand and -20.33 per thousand
      -0.01 per thousand, respectively. The delta18O value is low in winter and high
      in summer, but the values of d-excess is on the contrary; The spatial
      distribution shows that delta18O value at Zhangye is highest, followed by Hotan,
      and the lowest is at Urumqi; The highest of d-excess value is at Urumqi, followed
      by Hotan, the lowest is at Zhangye; The temperature effect of delta18O in
      precipitation is significant with the correlation coefficients of 0.85, 0.81 and
      0.86, respectively, and the rainfall effect does not exist; The modeled
      trajectory of vapor source showed there are two main paths all the year, which
      are from the Atlantic Ocean via Westerlies and the Arctic region, respectively,
      influence by different vapor sources, the seasonality of delta18O values lower in
      winter, higher in summer; In addition, according to the cryospheric environment,
      the correlation between delta18O in snow pack or ice core and the corresponding
      meteorological station record was significant, which reflects the variation of
      temperature efficiently.

PMID- 22624360
TI  - [Distributions and seasonal variations of total dissolved inorganic arsenic in
      the estuaries and coastal area of eastern Hainan].
AB  - The concentrations of total dissolved inorganic arsenic (TDIAs) were measured by
      Hydride Generation-Atomic Fluorescence Spectrometry (HG-AFS). Two cruises were
      carried out in the river, estuary, coastal area and groundwater of eastern Hainan
      in December 2006 and August 2007. The concentrations of TDIAs in the Wanquan and
      Wenchang/Wenjiao rivers and their estuaries, coastal area in December 2006 were
      4.0-9.4, 1.3-13.3, 13.3-17.3 nmol x L(-1), respectively. The concentrations of
      TDIAs in the Wanquan and Wenchang/Wenjiao rivers and their estuaries, coastal
      area in August 2007 were 1.6-15.5, 2.4-15.9, 10.8-17.6 nmol x L(-1),
      respectively. There was no significantly seasonal variation of TDIAs in the
      rivers and estuaries during the dry and wet seasons. Compared with other areas in
      the world, the concentration of TDIAs in the Eastern Hainan remained at pristine
      levels. TDIAs showed conservatively mixing in the both estuaries. The
      concentration of TDIAs of groundwater was below detection limit (BDL)-41.7 nmol x
      L(-1). The submarine groundwater discharge (SGD) to the coastal area was
      estimated in the drainage basin of Wenchang/Wenjiao river based on the average
      concentration of TDIAs in the groundwater and SGD water discharge, with the value
      of 1 153 mol x a(-1). Budget estimation indicated that the SGD discharge is one
      of the important sources of arsenic in the coastal area.

PMID- 22624361
TI  - [Mixing behavior of arsenic in the Daliaohe Estuary].
AB  - Mixing behavior of arsenic in the Daliaohe Estuary was studied. Twenty samples
      were collected from the Daliaohe Estuary during April, July and November, 2010
      and arsenic was determined by HG-AFS. The concentrations of arsenic varied from
      2.98-44.1, 1.19-14.6, 1.27-12.4 microg x L(-1) in April, July and November. The
      seasonal variation of arsenic content was significant. In July, the concentration
      of arsenic was lower than that in April, and higher than that in November. The
      data indicated that arsenic did not behave conservatively in April and November,
      but behaved conservatively in July. An important mobilization of dissolved
      arsenic was observed from the river up to halfway in the estuary in April and
      November, 2010. Both input flux (from river to estuary) and output flux (from
      estuary to coastal zone) of dissolved arsenic were calculated from statistical
      interpretations of the salinity profiles. Concentration of arsenic in the
      Daliaohe Estuary is higher than large systems, like the Changjiang Estuary and
      Zhujiang Estuary.

PMID- 22624362
TI  - [Variation characteristics and potential ecological risk assessment of heavy
      metals in the surface sediments of Bohai Bay].
AB  - The geochemical characteristics of eight heavy metals (Cd, Co, Cr, Cu, Ni, Pb, V
      and Zn) in two sediment cores from Bohai Bay, North China, were studied. Sediment
      samples were collected from 27 stations in spring 2008. A sequential extractions,
      procedure was used to gain their fractionation information. Five operationally
      defined fractions were obtained by this protocol, i. e. exchangeable (L1), bound
      to carbonates (L2), bound to Fe/Mn-oxides (L3), bound to organic matter and
      sulphides (LA), and residual fraction (R5). Combined with ecological risk in
      total contents and fraction, a series of results and viewpoints with regard to
      distribution characteristics of heavy metals were presented, as well as
      ecological risk and controlling factors. Heavy metals in sediments were mainly
      concentrated in the middle region with fine particle. The distributions of V, Ni,
      Cu, Pb, Co, Cd were mainly controlled by nature source, while Zn and Cr can be
      easily impacted by environment or human input. Coming from atmospheric deposition
      and riverine, Pb was different with other heavy metals. Sequential extractions
      suggested that V, Zn, Cr were mainly composed with residual fractions, while Co,
      Ni, Cu were dominated by labile fractions. The percentage of labile Co increased
      from inner to outside, labile Ni reached maximum at station A3, labile Cu and Pb
      concentrated in the middle of Bohai Bay, while Cu achieved maximum at station D1
      near Yellow River. Labile heavy metals were enriched near the estuary of Haihe
      River. The order of enrichment factors (EF) of heavy metals was Pb > Cd > Zn > Cr
      > V > Co > Cu > Ni. And the EF of Pb, Cd and Zn were above 1, suggesting that
      they could be polluted by exterior input, while the sediment quality was
      relatively good in general. The ratios of labile and residual fraction showed
      that V and Cr were clean, Zn was partly in slightly polluted, Co was mostly
      slightly polluted, Cu was from clean to moderately polluted, Ni was polluted from
      slightly to heavy, and Pb was polluted heaviest in all heavy metal. In
      conclusion, V, Cr and Co were clean, Cu and Zn may be polluted, while Pb was
      polluted heaviest.

PMID- 22624363
TI  - [Distribution of PAHs in surface seawater of Qingdao coast area and their
      preliminary apportionment].
AB  - The 15 parent PAHs in surface seawater from Qingdao coastal areas have been
      quantified by solid phase extraction-high performance liquid chromatography with
      fluorescent detection. The results showed that the concentration of total PAHs
      ranged from 8.23 ng x L(-1) to 272.02 ng x L(-1), with highest concentration near
      estuary and lowest at rural location. As for PAHs composition, 2, 3 ring PAHs
      were dominant, with percentage ranged from 52.2% to 93.8%, while the remaining
      were 4 to 6 ring PAHs which were ranged from 6.2% to 47.8%. The concentration of
      total PAHs correlates strongly with dissolved organic carbon (R = 0.944 7) in
      surface seawater. There was no significant fluctuation in the concentration and
      composition of PAHs in surface seawater from Qingdao bay area in a one-month
      period. The two ratios of paired PAH isomeric compounds, fluoranthene to
      fluoranthene plus pyrene[ Fl/(Fl + Py)] and anthracene to phenanthrene plus
      anthracene [An/(An + Ph)], for source apportionment suggested that various
      petroleum related sources, such as oil spill and petroleum combustion, were the
      major origin at most sampling sites, except in clean areas where PAHs were
      predominantly derived from coal and wood combustion.

PMID- 22624364
TI  - [Atmospheric deposition of PAHs in Dashiwei Karst Tiankeng Group in Leye,
      Guangxi].
AB  - In order to understand atmospheric deposition of polycyclic aromatic hydrocarbons
      impact on ecological environment of Dashiwei Karst Tiankeng Group in Leye County,
      Guangxi (National Geological Park), the dry and wet deposition samples around
      Dashiwei Tiankeng were collected by season for a year, and were analyzed
      utilizing GC-MS for 16 EPA PAHs. The results showed that PAH depositional fluxes
      ranged from 132.36-1 655.27 ng x (m2 x d)(-1), with an average value of 855.00 ng
      x (m2 x d)(-1). Weight of PAHs which deposited into Dashiwei Tiankeng was 51.98 g
      x a(-1), and the dominant PAH compounds are benzo[b] fluoranthene, chrysene,
      benzo[a] pryene, benzo[k]fluoranthene, anthracene, phenanthrene and naphthalene.
      Spatial distribution of PAHs around Dashiwei Tiankeng was: the east valley
      entrance > the south valley entrance > the north valley entrance > the west peak;
      seasonal variability of PAH depositional fluxes was: spring > summer > autumn >
      winter. Deposition fluxes of PAHs were 4.6 times higher in spring and summer than
      those in autumn and winter. The dominant PAH compounds were 4-6 rings PAHs in
      spring and summer, but the dominant PAH compounds were 2-3 rings PAHs in autumn
      and winter. PAH depositional fluxes in this study area were closely related with
      precipitation, wind direction, temperature, wind speed and location of pollution
      sources. PAHs increased in spring and summer in Dashiwei Karst Tiankeng Group,
      this could be transported by atmospheric movement from higher air temperature and
      lower elevation areas where industry developed in Guangxi.

PMID- 22624365
TI  - [Lead isotope signatures and source identification in urban soil of Baoshan
      district, Shanghai].
AB  - Two soil cores were collected from the Yuepu Park and a vegetable field near the
      Yunchuan Road in Baoshan district, Shanghai. Particle size, Pb content and Pb
      stable isotopic ratios were measured to examine Pb contamination status and its
      source. The results indicate that Pb concentration in the vegetable field soil
      and Yuepu park soil varies from 17.2 mg x kg(-1) to 34.8 mg x kg(-1) and 17.5 mg
      x kg(-1) to 36. 5 mg x kg(-1), respectively. The observed Pb isotopic ratios of
      vegetable field samples vary from 0.827 to 0.849 for 207Pb/206Pb, and 2.082 to
      2.101 for 208Pb/206Pb, while those of Yuepu Park samples range from 0.839 to
      0.848 and 2.089 to 2.097, respectively. Pb content, its enrichment factor (EF)
      and Pb stable isotopic ratios increase upward in both soil cores. EF values of
      surfacial (top 10 cm) vegetable field samples and park samples are mostly greater
      than 1.5, suggesting that higher Pb contents in topsoils are caused by
      anthropogenic activities. Compared with previous reports on Pb isotope signatures
      of different environmental materials in Shanghai, Pb isotopic ratios in the two
      soil cores are between those of Yangtze River intertidal sediments and the dust
      of coal combustion, and those of soil samples with EF > 1.5 are closer to the
      isotopic ratios of coal combustion dust. It indicates that topsoil in the Baoshan
      district is contaminated by dust derived from coal combustion.

PMID- 22624366
TI  - [Solute transport modeling application in groundwater organic contaminant source
      identification].
AB  - Investigation and numerical simulation, based on RT3D (reactive transport in 3
      dimensions)were used to identify the source of tetrachloroethylene (PCE) and
      trichloroethylene (TCE) in the groundwater of a city in the north of China and
      reverse the input intensity. Multiple regressions were applied to analyze the
      influenced factors of input intensity of PCE and TCE using Stepwise function in
      Matlab. The results indicate that the factories and industries are the source of
      the PCE and TCE in groundwater. Natural attenuation was identified and the
      natural attenuation rates are 93.15%, 61.70% and 61.00% for PCE, and 70.05%,
      73.66% and 63.66% for TCE in 173 days. The 4 source points identified by the
      simulation have released 0.910 6 kg PCE and 95.693 8 kg TCE during the simulation
      period. The regression analysis results indicate that local precipitation and the
      thickness of vadose zone are the main factors influencing organic solution
      transporting from surface to groundwater. The PCE and TCE concentration are found
      to be 0 and 5 mg x kg(-1) from surface to 35 cm in vadose zone. All above results
      suggest that PCE and TCE in groundwater are from the source in the surface.
      Natural attenuation occurred when PCE and TCE transporting from the surface to
      groundwater, and the rest was transported to groundwater through vadose zone.
      Local precipitation was one of the critical factors influencing the
      transportation of PCE and TCE to aquifer through sand, pebble and gravel of the
      Quaternary.

PMID- 22624367
TI  - [Quantitative method of representative contaminants in groundwater pollution risk
      assessment].
AB  - In the light of the problem that stress vulnerability assessment in groundwater
      pollution risk assessment is lack of an effective quantitative system, a new
      system was proposed based on representative contaminants and corresponding
      emission quantities through the analysis of groundwater pollution sources. And
      quantitative method of the representative contaminants in this system was
      established by analyzing the three properties of representative contaminants and
      determining the research emphasis using analytic hierarchy process. The method
      had been applied to the assessment of Beijing groundwater pollution risk. The
      results demonstrated that the representative contaminants hazards greatly
      depended on different research emphasizes. There were also differences between
      the sequence of three representative contaminants hazards and their corresponding
      properties. It suggested that subjective tendency of the research emphasis had a
      decisive impact on calculation results. In addition, by the means of sequence to
      normalize the three properties and to unify the quantified properties results
      would zoom in or out of the relative properties characteristic of different
      representative contaminants.

PMID- 22624368
TI  - [Study on the advanced pre-treatments of reclaimed water used for groundwater
      recharge].
AB  - To prevent groundwater contamination, pretreatments of reclaimed water are needed
      before the groundwater recharge. In this study, five treatments, including
      ultrafiltration (UF), ozonation, magnetic ion exchange (MIEX), UF coupled with
      ozonation and MIEX coupled with ozonation, were evaluated for their purification
      efficiencies of the reclaimed water and their influences on the following soil
      aquifer treatments. For organic matters in the secondary effluents, identified as
      dissolved organic carbon (DOC) and specific ultraviolet absorbance (SUVA), 20%
      DOC and 10% SUVA are removed by MIEX treatment with dose of 5 mL x L(-1), while
      only 10% DOC and no SUVA are removed by UF, but neither of these two
      pretreatments enhance the purification of soil aquifer treatments. Differently,
      SUVA of the secondary effluents are removed by 60%-79% by ozonation alone or
      coupled with UF/MIEX, increasing the biodegradability of the reclaimed water.
      These pretreatments significantly enhance the removal of organic matters by the
      following soil aquifer with DOC in the final effluents reducing to 1-2 mg x L(
      1). For nitrogen, MIEX can remove 25% NO3(-) -N, and ozonation can remove 72%
      NH4(+) -N. The soil aquifer treatment could efficiently remove NH4(+) -N to below
      0.5 mg x L(-1), while no obvious removal is detected for NO3(-) -N. In
      conclusion, more attentions should be paid to the organic matters and NO3(-) -N
      during the pretreatments of reclaimed water. Among all the pretreatments tested
      here, ozonation coupled with MIEX is capable of increasing the biodegradability
      of the reclaimed water and removing NO3(-) -N, which is a good choice for the
      pretreatment of groundwater recharge.

PMID- 22624369
TI  - [Influence of Ruditapes philippinarum aquaculture on benthic fluxes of biogenic
      elements in Jiaozhou Bay].
AB  - Nutrient excretion rates and the impact of Ruditapes philippinarum on benthic
      nutrient fluxes were measured by incubation experiments, and these results were
      used to assess the effect of R. philippinarum aquaculture on nutrient recycling
      in Jiaozhou bay. Our research indicates that the bioturbation of R. philippinarum
      would modify biogeochemical progresses in sediment, and restrain nutrients
      excreted by R. philippinarum releasing to overlying water. Only 37% DIN and 34%
      PO4(3-) -P excreted by R. philippinarum were released to seawater across the
      sediment-water interface due to bioturbation of R. philippinarum. According to
      the reduction of nutrient exchange across the sediment-water interface by
      bioturbation, only 19% (N) and 17% (P) of biogenic elements fed by R.
      philippinarum can be recycled and returned to seawater, while the others would be
      removed from seawater in Jiaozhou Bay. The ratios of Si: N and Si: P of nutrients
      released from sediment to seawater with bioturbation of R. philippinarum were
      about 5:18 and 5:1, which were far less than Redfield ratios. Therefore,
      aquaculture of R. philippinarum should promote BSi biodeposition to sediment and
      reduce the nutrient ratios of Si: N and Si: P in seawater of Jiaozhou bay.

PMID- 22624370
TI  - [Influence of spatial difference on water quality in Jiuxiang River watershed,
      Nanjing].
AB  - Exploring the quantitative relationship between landscape characteristics and
      surface water quality indicators can provide important information to urban
      landscape planning and water environment protection. Jiuxiang River watershed in
      Nanjing city, being as a typical case study area, its landscape classification
      maps was conducted in 2009 by remote sensing digital images interpretation. Based
      on the remote sensing images and real-time monitoring data from October 2009 to
      September 2010, geospatial analysis and statistical analysis were integrated to
      explore the relationship between landscape composition, landscape pattern
      (landscape-level and class-level) and river water quality at the subwatershed
      scale. Results showed that most of landscape compositions influenced river water
      quality. Percentage of built-up land and unused land was positively related to
      total nitrogen (TN), total phosphorus (TP), ammonia nitrogen (NH4(+) -N) and
      permanganate index, while percentage of forestland showed a negative
      relationship. At the landscape level, the water quality was good when the size of
      patch was big. But at class-level, the aggregated distribution of the built-up
      land, unused land and arable land might cause TN, TP, permanganate index and
      NH4(+) -N concentration increased. But the aggregated distribution of the
      forestland had the opposite effect on water quality indicators.

PMID- 22624371
TI  - [Temporal and spatial variation of non-point source nitrogen in surface water in
      urban agricultural region of Shanghai].
AB  - To know the temporal and spatial variation characteristics of non-point source
      nitrogen in surface water in urban agricultural region, and reveal the effect of
      non-point source nitrogen pollution on the quality of surface water, the contents
      of total nitrogen and inorganic nitrogen species in surface water were
      continuously monitored in Orchard Village, Nanhui District, Shanghai. The results
      were obtained as follows: (1) Spatial distribution of nitrogen in surface water
      is affected by hydrological periods and land use type. Mass concentration of
      nitrate nitrogen (NN) is high and that of ammonium nitrogen (AN) is low in
      surface water affected by the orchard, and the discrepancy of nitrogen
      concentration is high in wet season and low in dry season. Mass concentrations of
      NN and AN in surface water affected by residential region and factories show
      little difference, and the discrepancy of nitrogen concentration is high both in
      wet season and in dry season. (2) Winter and summer monsoons may affect the
      spatial distribution of nitrogen in surface water in the studied area. (3)
      Spatial variation of total nitrogen (TN), NN and AN is the highest in spring rain
      period, and it is higher in plum rain period and winter brief rain period than
      that in autumn rain period and summer brief rain period. Nitrite nitrogen (SNN)
      shows contrary spatial variation. (4) Dissolved organic nitrogen (DON, mass
      fraction in TN is 76.1%) is the main species in surface water in orchard region
      in May, while the dissolved inorganic nitrogen (DIN, mass fraction in TN is
      83.2%) in other months. (5) The temporal variation of NN in orchard region is
      higher than that in residential region, while that of AN and TN in residential
      region is higher than that in orchard region.

PMID- 22624372
TI  - [Migration and transformation of heavy metals in street dusts with different
      particle sizes during urban runoff].
AB  - The heavy metal pollution in runoff caused by street dust washoff has been an
      increasingly prominent problem in the context of rapid urbanization in China.
      Based on measurement of heavy metal contents in street dusts with different
      particle sizes and an experiment of street dust washoff using simulated rainfall,
      we analyzed the role of particle size of street dust in heavy metal pollution,
      and the variation in geometrical forms of heavy metals during street dust
      washoff. Our results showed that the heavy metal concentration decreased from
      "static" street dust to "dynamic" runoff particulate in the same diameter
      particles. Heavy metals in street dust were dissolved and extracted during
      washoff. The average loss proportion of the five metals (Cr, Cu, Ni, Pb, Zn) were
      24.3%, 56.8%, 34.3%, 22.8%, 27.3%, respectively. The loss proportion increased
      with the decrease of the particle size of street dust. Proportion of extracted
      form dust was higher in street than that in washoff samples, which suggested some
      dissolved loss in water. In washoff samples, dissolved metals of waterphase did
      not have significant changes; however, heavy metals with particle state in
      waterphase reduced rapidly during runoff. Meanwhile, heavy metals of solid-phase
      particle reduced during runoff. Street dust with small particle size had higher
      loss rate during runoff. The variation rate of street dust loss among different
      particle sizes varied from 4.6% to 62.1%. Street dust with smaller particle size
      had higher migration ability in runoff, which was more risky to urban water
      pollution.

PMID- 22624373
TI  - [Treatment studies of industrial rainoff with a new type of constructed wetland].
AB  - According to water characteristics of industrial rain runoff in a catchment of
      Tongsha reservoir, Dongguan city, an improved baffled constructed wetland (BCW)
      was used for purification experiment study of simulated and on-the-spot rain
      runoff. The purification effects of simulated rain runoff were compared in
      different operated phases of BCW. Meanwhile, the variation of the pollutants
      (COD, SS, TN, TP, NH4(+) -N, Pb, Zn, Cu) along the BCW and their removal
      mechanism were analyzed and discussed, respectively. In the simulated experiment,
      the effluent water quality of BCW system met the needs of Environmental Quality
      Standard for Surface Water( GB 3838-2002) III, besides TN met IV, and most of the
      pollutants were removed in the front of the BCW. In the purification study of on
      the-spot rain runoff, removal rate of COD, SS, TN, TP and NH4(+) -N were 90.9%,
      97.0%, 83.4%, 92.2% and 90.0%, respectively; removal rate of Pb, Zn and Cu were
      98.4%, 94.1% and 93.6%, respectively. The effluent met the grade III. Results
      showed that there was remarkable treatment performance of industrial catchment
      rain runoff when BCW system was used, which also can withstand strong shock load.
      Moreover, a modest variation of temperature affected the removal of pollutants in
      the BCW insignificantly.

PMID- 22624374
TI  - [Emergent retention of organic liquid by modified bentonites: property and
      mechanism].
AB  - In this study, the property and mechanism of modified bentonites synthesized by
      long chain quaternary ammonium compounds which would be used in the emergent
      retention of typical organic liquid (benzene, chlorobenzene, nitrobenzene and
      diesel) were investigated and a pilot-scale simulation experiment was conducted.
      The unit retention capacity of modified bentonites for organic liquid (2.83-9.01
      g x g(-1)) was much higher than that of conventional retention agents (0.28-1.17
      g x g(-1)). The property and amount of the surfactants used and viscosity of
      organic liquid had a significant influence on the retention capacity of modified
      bentonites for the organic liquid, for example, the bentonites modified by
      cetyltrimethylammonium (CTMAB) with an adding quantity of 100% CEC showed the
      highest efficiency in the retention of organic liquid. In the simulation
      experiment, organic liquid could be retained effectively within 30 min by
      emergent retention device with modified bentonites and the retention efficiency
      might reach positively up to 90%. Results indicated that modifications using
      surfactants could enhance the hydrophobicity and interlayer space of the modified
      bentonites and make their retention capacities for organic liquid improved.

PMID- 22624375
TI  - [Production of peroxide hydrogen in Chattonella ovata Hong Kong strain].
AB  - The growth characteristics of Chattonellea ovata Hong Kong strain (COHK) under
      different salinity and nutrient conditions and production of peroxide hydrogen
      (H2O2) in different growth phase were investigated in laboratory unialgal culture
      experiment. The results showed that high concentration of H2O2 was reached during
      the logarithmic phase from 4th to 8th days, corresponding to the maximum value of
      2.91 x 10(-4) nmo x cell(-1) on the 6th day. When the N: P ratios were 16: 1,
      32:1 and 64: 1, COHK possessed the relatively high growth rate and cell
      concentration, however, growth rate of COHK was lower with the N: P ratios of 4:
      1 and 8: 1. The H2O2 concentration reached the highest (1.26 x 10(-4) nmol x
      cell(-1)) with the N: P ratio of 4: 1, which suggested that production of H2O2
      was reversely related to the growth of COHK. The optimum salinities for COHK were
      20 and 25. When the salinities were 10, 15 and 30, the growth rate of COHK was
      lower, showing lower and higher salinities inhibited the growth of COHK. Salinity
      also influenced the production of H2O2. The highest concentration of H2O2 among
      the experiments, 2. 2 x 10(-4) nmol x cell(-1), was observed at the salinity of
      10, while there was no significant difference of H2O2 concentration from the
      salinity range of 15 to 30. The optimal Fe(3+) concentration for the growth of
      COHK was from 0.2 x 10(-8) to 1 x 10(-8) mol x L(-1), where growth rate were
      relatively higher. Growth rate of COHK was depressed in absence (0 mol x L(-1))
      and high concentration of Fe3+ (5 x 10(-8) mol x L(-1)), with which H2O2
      concentration was 0.97 x 10(-4) and 0.95 x 10(-4) nmol x cell(-1), respectively.

PMID- 22624376
TI  - [Characteristics study of extracellular active substance of Bacillus sp. B1 on
      Phaeocystis globosa].
AB  - The algicidal bacterium named B1 which was identified as Bacillus sp. was
      isolated from red tide water in Xiangzhou shipside of Zhuhai. The algicidal mode
      of algae-lysis bacterium B1 and the microstructure of algal cells in the algae
      lysing process were studied. In order to explore the properties of extracellular
      algicidal substances, the sterile condensed bacteria-free filtrate was dialysed,
      sedimentated by ethanol, extracted by organic solvents and exposed in different
      heat and pH variations. The results showed that the sterile condensed bacteria
      free filtrate could effectively dissolve Phaeocystis globosa (P. globosa), the
      removal rate was 94.9%, B1 excreted algae-lysing substances to inhibit the growth
      of algae indirectly. Algicidal process under the visual field of microscope
      demonstrated that the alga cell rounded and the cell wall lost integrity after 16
      h, the algae cell lysed and cellular substances released after 56 h. The
      molecular weight of the extracellular algae-lysing components of B1 are less than
      3 500, the algicidal substances have strong polarity and heat-tolerant, which
      still had a strong algae-lysing effect after being treated at 121 degrees C, and
      the removal rate was 92.6%. The algae-lysing ability was stronger while the pH
      value was kept at 9.0, ethanol can separate extracellular algae-lysing components
      from other components efficiently. The algae-lysing components may be non
      bioactive molecules which contain acidic or alkaline groups, and may not be
      protein, nuclear acid and polysaccharides.

PMID- 22624377
TI  - [Effects of sediment on the growth of Microcystis and Anabaena in Yanghe
      reservoir].
AB  - Batch culture experiments were used to study the effect of leachate from sediment
      of Yanghe reservoir on the growth of Microcystis and Anabaena isolated from
      Yanghe reservoir. The results showed that the growth of Microcystis was
      significantly inhibited when the addition of anaerobic leachate from sediment in
      M11 culture medium was high (> or = 20% V/V). The maximum biomass of Microcystis
      was lower than that grown in pure M11 culture medium. But there was an obvious
      promotion on the growth of Anabaena when anaerobic leachate from sediment was
      added. The growth rate of Anabaena increased 36.6%, 47.2% and 36.0%,
      respectively, compared to M11 culture medium when adding 2%, 20% and 50% (V/V)
      anaerobic leachate. Compared to adding anaerobic leachate, aerobic leachate had
      no influence on the growth of Microcystis, while the growth rate of Anabaena was
      promoted by aerobic leachate. The growth rate of Anabaena increased 37.2%
      compared with M11 when adding 20% (V/V) of aerobic leachate. But after addition
      of Fe-citrate to the mixed culture medium (50% M11 culture medium +50% anaerobic
      leachate), the maximum biomass of Microcystis significantly increased. The
      results suggest that high organic matter concentration decreases iron
      availability for Microcystis.

PMID- 22624378
TI  - [New-type electrodeless excilamp for advanced treatment on nitrogen-heterocyclic
      compounds (NHCs) in aqueous solution].
AB  - A novel 206 nm excilamp generated by microwave-driven Kr/I2 mixtures was employed
      for nitrogen-heterocyclic compounds (NHCs) degradation in aqueous solution. The
      photodissociation efficiencies of indole and quinoline with 206 nm excilamp were
      estimated on the basis of removal efficiency of targeted compounds and the loss
      of total organic carbon (TOC). The results indicated that removal efficiency of
      20 mg x L(-1) indole was as high as 62.0% after 80 min and TOC loss efficiency of
      50.7% for 150 min. The irradiation time, initial concentration and pH value had
      some influences on quinoline degradation. Indole removal efficiency and TOC loss
      was markedly higher than that of quinoline under the same condition. The
      intermediates were identified qualitatively by gas chromatography/mass spectrum
      (GC/MS) with headspace sampling after they were extracted by rotary evaporator.
      GC/MS analysis indicated that indole and quinoline underwent ring-open
      dissociation under 206 nm irradiation, as a result, benzene, xylene, acetate,
      aldehyde, as well as ester compounds were formed, while indole aggregation
      reaction occurred during indole photodegradation. At last, degradation mechanisms
      of quinoline and indole in aqueous media with 206 nm excilamp were proposed on
      the basis of intermediates.

PMID- 22624379
TI  - [Preparation and electro-catalytic characterization on La/Ce doped Ti-base lead
      dioxide electrodes].
AB  - Ti-base lead dioxide electrodes (Ti/PbO2) doped with rare earth La, Ce were
      prepared by the electrode position. The surface morphology and crystal structure
      of the electrodes was analyzed by scanning electron microscopy (SEM) and X-ray
      diffraction (XRD), the results showed that, microstructure and crystal
      orientation of electrode surface changed after doping rare earth La, Ce, which
      made the electrode surface more dense and uniform. The electrochemical properties
      of the electrodes were tested by linear sweeping (LS) and cyclic voltammogram
      (CV), the experimental results show that, La, Ce doping improved the electrode
      overpotential of oxygen evolution and the peak current density, promoted the
      catalytic performance of the electrode. Different doping amount of modified
      electrodes were used to degrade methylene blue simulative dyeing wastewater, the
      results showed that, electrodes doped La and Ce respectively 8.0 g x L(-1) and
      5.0 g x L(-1) have the best degradation efficiency and catalytic activity, for
      example, the removal of MB and its COD respectively researches 83.85%, 79.95% and
      79.18%, 76.21%. The possible degradation pathways and mechanisms were also
      discussed.

PMID- 22624380
TI  - [Study on decolorization of triphenylmethane dyes by DTT].
AB  - Decolorization of triphenylmethane dyes by DTT was researched. For malachite
      green, content of DTT in reaction system was optimized to investigate the
      quantitative relation between DTT and malachite green and the decolorization
      capacity of DTT was confirmed. Effect of pH of reaction system on reducibility of
      DTT was explored. The results indicated 4 mol malachite green could be
      decolorized by 1 mol DTT averagely within 1 min, when pH of the reaction system
      was above 5. The decolorization rate was up to 97%. Decolorization product of
      malachite mreen was corroborated to be its leuco form by HPLC analysis. Some
      insoluble compounds, which could be the complex products of leuco malachite green
      with DTT, were formed during the decolorization reaction. Decolorization of
      crystal violet, brilliant green and basic fuchsin by DTT was tested further, and
      the decolorization rates were all above 85%, which suggested DTT was a broad
      spectrum decolorization agent for triphenylmethane dyes.

PMID- 22624381
TI  - [Influences of pH and complexing agents on degradation of reactive brilliant blue
      KN-R by ferrous activated persulfate].
AB  - The influences of pH and complexing agents on degradation of reactive brilliant
      blue KN-R by ferrous activated persulfate were investigated, and finally the
      complexed and the uncomplexed system were compared. Because the lower the pH the
      more quickly will be the dissociation of S2O8(2-) to the SO4(-*) and the ORP of
      the dominant radical SO4(-*) in the acidic condition is higher than the dominant
      radical *OH in the alkaline condition, KN-R degradation rates in acidic condition
      are far outweigh in the neutral and alkaline conditions. When pH value was 3, the
      residual rate of KN-R was 17.0% within 3 hours by EDTA system with the lowest PS
      consumption rate 32.3%, so EDTA was the best complexing agent choice in acidic
      condition. When pH value was 7, the residual rates of KN-R were 11.3%, 12.4%
      within 3 days by EDTA, citric acid system with the PS residual rates 28.9%, 28.0%
      respectively, so EDTA, citric acid were the better choices in the neutral
      condition. When pH value was 10, glucose acid, citric acid, EDTA and tartaric
      acid systems all had the similar KN-R degradation rates and PS residual rates, so
      all could acted as the complexing agents, when the system contained trace amounts
      of ferrous, the addition of complexing agent would greatly improve the
      degradation rate of pollutant, from original 52.5% to 79.3% of 3 d, so PS is
      suitable for in situ chemical oxidation (ISCO).

PMID- 22624382
TI  - [Degradation kinetics of ozone oxidation on high concentration of humic
      substances].
AB  - Humic substance oxidation (HS) degradation by ozone was kinetically investigated.
      The effects of O3 dosage, initial pH, temperature and initial concentration of HS
      were studied. Under the conditions of 3.46 g x h(-1) ozone dosage, 1 000 mg x L(
      1) initial HS, 8.0 initial pH and 303 K temperature, the removal efficiencies of
      HS achieved 89.04% at 30 min. The empirical kinetic equation of ozonation
      degradation for landfill leachate under the conditions of 1.52-6.10 g x h(-1)
      ozone dosage, 250-1 000 mg x L(-1) initial HS, 2.0-10.0 initial pH, 283-323 K
      temperature fitted well with the experimental data (average relative error is
      7.62%), with low activation energy E(a) = 1.43 x 10(4)J x mol(-1).

PMID- 22624383
TI  - [Index of stability and its mechanisms of aerobic granular system using volume
      based information entropy].
AB  - Autotrophic nitrification granular sludge was cultivated in a sequencing batch
      reactor (SBR), the information entropy of volume distribution decreased from 2.05
      (27 d, granules were firstly observed) to 1.85 (95 d) during granulation period.
      And the driving force for the decrease of information entropy could be ascribed
      to the washing out of flocs by means of the hydraulic selection pressure. After
      the granules formation stage finished, the median settling velocity of the
      granules system was 6.27 m x h(-1) and the information entropy of volume
      distribution would not be controlled by the settling velocity selection pressure
      (6 m x h(-1)). It was found that the size, settling velocity and the volume-based
      information entropy periodically changed. The mean, minimum and maximum of
      information entropy were 2.16, 1.79 and 2.63, respectively, during the period
      from 122 d to 579 d. The mean size varied by the pattern of increase and decrease
      periodically. The driving force for the fluctuation of the information entropy
      was the smashing of the larger granular and the volume fragmentation growth, and
      the volume distribution of the information entropy could well indicate the
      stability of granular sludge systems.

PMID- 22624384
TI  - [Relationship between physicochemical characteristics of activated sludge and
      polymer conditioning dosage].
AB  - Jar test was employed to determine the relationship between physicochemical
      characteristics of activated sludge (AS) and polymer conditioning dose. The
      evolutions of indexes representing the AS physicochemical characteristics, such
      as the viscosity of AS centrifugal supernatant, zeta potential and surface charge
      density of colloids in it, size, fractal dimensions and strength of AS flocs,
      with polymer doses of CZ-8698 in flocculation conditioning process were recorded
      and analyzed. In addition, the difference in determining the optimum dosage of AS
      conditioner was identified among the aforementioned indexes. The results showed
      that CZ-8698 doses had a great impact on the dewaterability and physicochemical
      characteristics of AS. The range for optimum CZ-8698 dose was 4.28-7.13 g x kg(
      1) on the basis of capillary suction Time (CST) and specific resistance to
      filtration (SRF) test, and the corresponding values for CST and SRF were (12.62
      +/- 1.39)s and 0.56 x 10(12)m x kg(-1), respectively. In this optimum range, both
      the zeta potential and surface charge density of colloids in AS centrifugal
      supernatant changed into positive values from negative ones, and AS flocs showed
      the most irregular boundary or surface and much compact structure, which was
      demonstrated by their fractal dimensions of 1.09 (one-dimensional fractal
      dimension, D1) and 1.51 (two-dimensional fractal dimension, D2). Although AS
      flocs grow up to millimeters scale with the increase of CZ-8698 doses, the
      strength of these flocs gradually tended to keep constant at the conditioner
      doses higher than 4.60 g x kg(-1). Furthermore, when conditioner dosage was much
      less than above optimum dosage range, the viscosity of AS centrifugal supernatant
      reach the minimum value (1.24 +/- 0.04) mPa x s.

PMID- 22624385
TI  - [Research of aerobic granule characteristics with different granule age].
AB  - In the SBR reactor, we studied the different style, physicochemical
      characteristic, pollutants removal and microbial activity between the short age
      and long age aerobic granule, respectively. The short age aerobic granule was
      cultivated from activated floccules sludge and the other was gotten from aerobic
      granular sludge which was operated stably more than one year. The results
      indicated that the wet density, the specific gravity and integrated coefficient
      (IC) of the short age aerobic granule were 1.066 g x cm(-1), 1.013 g x cm(-3) and
      98.7%, respectively. And that of long age were 1.026 g x cm(-3), 1.010 g x cm(-3)
      and 98.4%, respectively. All of them were higher than the long age aerobic
      granule. The mean diameters of them were 1.9 mm and 2.2 mm, respectively. The
      settling velocity of short age and long age aerobic granule were 0.005-0.032 m x
      s(-1) and 0.003-0.028 m x s(-1), respectively, and two kinds of aerobic granule
      settling velocity increased with the diameter increased. SVI of the former was
      lower. The COD removal rates of two aerobic granules were above 90%, and the
      NH4(+) -N removal rates of them were about 85%. The results of the COD effluent
      concentration, NH4(+) -N effluent concentration and the pollutants concentration
      in a typical cycle indicated that the short age aerobic granule had better
      pollutants removal efficiency. The TP removal rates of them were between 40% -90%
      and 32% -85%, respectively. The TN removal rates of them were about 80%. The
      SOUR(H) SOUR(NH4) and SOUR(NO2) of the short age aerobic granule were 26.4, 14.8
      and 11.2 mg x (h x g)(-1), respectively. And that of long age were 25.2, 14.4 and
      8.4 mg x (h x g)(-1), respectively. In summary, the aerobic granule had
      significantly different physical and chemical characteristics because of
      different granule age, and the short age aerobic granule exhibited better
      pollutants removal ability, higher microbial activity and more stability than the
      long age aerobic granule.

PMID- 22624386
TI  - [Effect of size and number of aerobic granules on nitrification and
      denitrification].
AB  - Based on experimental results, a one dimension dynamic model was developed for
      describing the growth, maintenance and decay processes of microbes using multi
      substances, and consequently, the effect of size and number of aerobic granules
      on nitrification and denitrification were investigated. It was found that the
      consuming of ammonia nitrogen increased with the larger number of granules given
      the same biomass amount, indicating that the consumption of ammonia was dependent
      on the surface area of granules. The resulting amount of NO2(-) -N and NO3(-) -N
      was dependent not only on the amount but also on the diameter of granules, and
      the effect of the diameter became negligible only when the ammonia concentration
      was very low, suggesting the penetration depth of oxygen determines the
      production of NO2(-) -N and NO3(-) -N. Regarding on denitrification, for those
      granules with the diameter more than 1 000 microm, the denitrification increased
      with the increase of diameter, however, for those ones less than 1 000 microm the
      effect of diameter became negligible, indicating that the limitation of oxygen
      diffusion in granules of big granules more than 1 000 microm could help the
      process of denitrification.

PMID- 22624387
TI  - [Optimization and comparison of nitrogen and phosphorus removal by different
      aeration modes in oxidation ditch].
AB  - The oxidation ditch operation mode was simulated by sequencing batch reactor
      (SBR) system with alternate stirring and aeration. The nitrogen and phosphorus
      removal efficiencies were investigated in two different aeration modes: point
      aeration and step aeration. Experimental results show that oxygen is dissolved
      more efficiently in point aeration mode with a longer aerobic region in the same
      air supply capacity, but dissolved oxygen (DO) utilization efficiency for
      nitrogen and phosphorus removal is high in step aeration mode. Nitrification
      abilities of the two modes are equal with ammonia-nitrogen (NH4(+) -N) removal
      efficiency of 96.68% and 97.03%, respectively. Nitrifier activities are 4.65 and
      4.66 mg x (g x h)(-1) respectively. When the ratio of anoxic zones and the
      aerobic zones were 1, the total nitrogen (TN) removal efficiency of point
      aeration mode in 2, 4 or 7 partitions was respectively 60.14%, 47.93% and 33.7%.
      The total phosphorus (TP) removal efficiency was respectively 28.96%, 23.75% and
      24.31%. The less the partitions, the higher the nitrogen and phosphorus removal
      efficiencies, but it is in more favor of TN removal. As for step aeration mode
      with only one partitioning zone, the TN and TP removal efficiencies are
      respectively 64.21% and 49.09%, which is better than in point aeration mode, but
      more conducive to the improvement of TP removal efficiency. Under the condition
      of sufficient nitrification in step aeration mode, the nitrogen and phosphorus
      removal is better with the increase of anoxic zone. The removal efficiencies of
      TN and TP respectively rose to 73.94% and 54.18% when the ratio of anoxic zones
      and the aerobic zones was increased from 1 : 1 to 1. 8 : 1. As the proportion of
      anoxic zones was enlarged further, nitrification and operation stability were
      weakened so as to affect the nitrogen and phosphorus removal efficiencies.

PMID- 22624388
TI  - [Effect of acidification on the dewaterability of sewage sludge in bioleaching].
AB  - Batch experiments were performed to exploit the effect and the mechanism of
      bioleaching on sludge dewaterability by the inoculation of Acidithiobacillus
      ferrooxidans LX5 in this study. Besides, chemical leaching experiments using
      sulphuric acid were also performed as control to study the effect of
      acidification on sludge dewaterability. During the processes of both biological
      and chemical leaching, Zeta potential, cell lyses, morphology and structure of
      sludge flocs were monitored. Results showed that along with the acid production
      and hence the decrease of pH during bioleaching, the specific resistance of
      bioleached sludge decreased systematically from 1.81 x 10(12) m x kg(-1) to 0.59
      x 10(12) m x kg(-1), whilst Zeta potential increased from -25.2 mV to 9.6 mV, and
      the natural sedimentation rate increased to as high as 48% at pH 2.90. In
      chemical leaching, the specific resistance decreased continuously to a minimum
      value of 2.6 x 10(12) m x kg(-1) at pH 3.35 and then started to increase. Zeta
      potential increased with the decrease of pH, and reached zero at pH 2.90. At
      strong acid condition, sludge cells could be decomposed, resulting in the
      increase of total dissolved phosphorus in centrifugal liquor of chemical leached
      sludge. However, this phenomenon was not observed in bioleaching process because
      that the phosphorus was utilized by the abundant microorganism in system.
      Observation by SEM showed that there was no obvious change in the flocs structure
      of both sludge at pH 3.35 except for that some secondary minerals appeared only
      in bioleached sludge. These results revealed that decrease of absolute value of
      Zeta potential and formation of secondary minerals caused by bioleaching were
      responsible for the improvement of sludge dewaterability.

PMID- 22624389
TI  - [Microbial ecology analysis of the biofilm from two biological contact oxidation
      processes with different performance].
AB  - This study investigated the performance of one-step aerobic biological oxidation
      process and anoxic/aerobic two-step biological oxidation process treating modeled
      river water containing low carbon and rich ammonia. Biofilm microbial ecology was
      analyzed with multiple molecular technologies including PCR-DGGE, FISH/CLSM and
      FISH/FCM to investigate the succession of bacteria community and space
      distribution along with abundance of the main functional bacteria, and to
      research the micro-influential factors and the mechanism of different biological
      contact oxidation processes for their performance. Results showed that two-step
      contact oxidation process achieved higher removal percentage than that of the one
      step process, with COD and NH4(+) -N removal enhanced about 10% and 32%-59%,
      respectively. A much thicker biofilm was obtained by the one-step process
      compared to the two-step process, and nitrobacterium was mainly distributed in
      the depth of 180-200 microm and 105-125 microm, respectively. PCR-DGGE results
      found that the two-step process demonstrated less microbial diversity than that
      of the one-step process, FISH/FCM results showed that ammonia oxidizing bacteria
      (AOB) and nitrite oxidizing bacteria (NOB) abundance increased in the two-step
      process with the increase of operation time, while that of the one-step process
      declined. Experiment results demonstrate that functional partitioning of the
      anoxic-aerobic two-step biological contact oxidation process could be in favor
      for harvesting nitrobacteria and other special bacteria in different reactor
      spaces, which can improve removal efficiency for organics and ammonia finally.

PMID- 22624390
TI  - [Altered microbial communities change soil respiration rates and their
      temperature sensitivity].
AB  - Inoculating common sterilized soil with different non-sterilized soils was used
      to investigate the potentials of altered microbial communities to change rate and
      temperature sensitivity of soil microbial respiration. Results showed that
      accumulative CO2 emission of sterilized Hailun black soils inoculated with non
      sterilized Harbin black soil, Fengqiu fluvo-aquic soil and Qiyang red soil were
      684.25, 753.97 and 644.91 microg, respectively, at 15 degrees C; were 963.06, 1
      015.44 and 852.31 microg, respectively, at 25 degrees C; and were 1 252.55,
      380.36 and 1 177.88 microg, respectively, at 35 degrees C. The soil accumulative
      CO2 emissions increased with pH of inoculant soils, but did not relate to organic
      content of and geographical distance from inoculant soils. Difference of
      microbial respiration rates among the three inoculant soils kept for 104, 277 and
      1 177 h at 15 degrees C, 25 degrees C and 35 degrees C, respectively. Temperature
      sensitivity quotients (Q10) of microbial respiration of sterilized Hailun black
      soils inoculated with non-sterilized Harbin black soil, Fengqiu fluvo-aquic soil
      and Qiyang red soil were 1.63, 1.49 and 1.80, respectively, during 0-104 h; were
      1.43, 1.39 and 1.46, respectively, during 0-277 h and were 1.35, 1.35 and 1.35,
      respectively, during 0-1 609 h. The Q10 decreased with pH of inoculant soils and
      incubation time. The results suggest that altered microbial community would
      change rate and temperature sensitivity of soil microbial respiration.

PMID- 22624391
TI  - [Storages and distributed patterns of soil organic carbon and total nitrogen
      during the succession of artificial sand-binding vegetation in arid desert
      ecosystem].
AB  - Soil carbon pool acts as the largest one of carbon pools in the terrestrial
      ecosystem. The storages and distributed patterns of soil organic carbon (SOC) and
      total nitrogen (TN) evaluated accurately are helpful to predict the feedback
      between the terrestrial ecosystem and climate changes. Based on the data about
      bulk density, content of SOC and TN at 0-100 cm soil profile, the density of SOC
      and TN at the temporal (chronosequence of artificial vegetation) and spatial
      (vertical) distributed patterns have been estimated. The results indicated that
      storages of SOC and TN at 0-100 cm depth increased with the chronosequence of
      artificial vegetation. The storages of SOC and TN showed the same tendency with
      the succession time of artificial vegetation. Storages of SOC and TN
      significantly increased at the early stage of banding sand by artificially
      vegetation (< 16 a), then piled up at the mid-stage (16-25 a), and markedly
      increased at the late stage (> 25 a). The variation of storages mainly occurred
      in the 0-20 cm depth. The storages decreased with the soil vertical depth. At the
      early stage of banding sand, increase in storage included every depth (0-100 cm).
      Whereas, at the later stage, increase in storage at 0-20 cm depth was main, and
      increase in the 20-100 cm was inconspicuous. The accumulation of storage at the
      shallow soil depth was more notability with the succession of artificial
      vegetation. The distributed pattern of storage in SOC and TN has been confirmed
      in arid desert regions below 200 mm annual precipitation. This was beneficial to
      understand the carbon cycle and to predict the feedback relationship between
      desert ecosystem and climate changes.

PMID- 22624392
TI  - [Factors controlling soil organic carbon and total nitrogen densities in the
      upstream watershed of Miyun Reservoir, North China].
AB  - Effects of climate (temperature and precipitation), topography (elevation and
      slope), soil properties (soil bulk density, pH, water and clay contents) and land
      use on soil organic carbon (SOC) and total nitrogen (TN) densities were
      investigated in the study to identify dominant factors controlling SOC and TN
      densities in the upstream watershed of Miyun Reservoir of North China by soil
      sampling, laboratory analysis and statistical analysis. Results showed that SOC
      and TN densities in the 0-20 cm soil layer were 4.77 kg x m(-2) and 0.41 kg x m(
      2) in forestland, 6.79 kg x m(-2) and 0.69 kg x m(-2) in grassland, 2.90 kg x m(
      2) and 0.30 kg x m(-2) in cropland, respectively. Significant differences in SOC
      and TN densities were observed among the three land uses. Soil water content,
      land use, slope, soil pH and clay content were the most significant factors
      controlling SOC density, while land use, soil clay and water contents were the
      most significant determinants of TN density. Climate, topography and soil
      properties jointly explained 63.6% and 53.4% of SOC and TN densities variability,
      respectively, while environmental factors and land use together explained 67.6%
      and 57.8% of variations in SOC and TN densities, respectively. Clearly,
      environmental variables were more important for SOC and TN densities variability
      than land use in the study area. Therefore, establishing a high-spatial
      resolution database of environmental factors is a key to more accurate
      assessments of SOC and TN stocks on a regional scale.

PMID- 22624393
TI  - [Impact of microbial aggregating agents on soil aggregate stability under
      addition of exogenous nutrients].
AB  - In this study, we investigated the effects of biological aggregating agents
      (fungal hyphae and microbial extracellular polysaccharides) soil aggregate (with
      different sizes) stability under addition of exogenous nutrients. The exogenous
      nutrients included glucose and ammonium nitrate. Experiments were conducted in a
      30 d incubation period with three treatments: (1) the control (0.5 mg x g(-1)
      soil); (2) CN5 (0.5 mg x g(-1) soil, 0.1 mg x g(-1) soil, C/N = 5); (3) CN10 (0.5
      mg x g(-1) soil, 0.05 mg x g(-1) soil, C/N = 10). Results showed that soil
      respiration rates were not significantly different among the three treatments,
      with maximums being about 3.10 mg x (h x kg)(-1), indicating that the impact of
      inorganic nitrogen fertilizer was not obvious in a short term. Aside from 5 d,
      macroaggregates amount of CK (15.67%) was observably lower than those of CN5
      (25.32%) and CN10 (24.63%), there were no remarkable discrepancies among 3
      treatments in other incubation period. The insignificant difference in the
      aggregate amounts among the three treatments suggested that the influence of
      glucose on microbial activities surpassed the inorganic nitrogen fertilizer in
      shortterm in the study.

PMID- 22624394
TI  - [Adsorption of aflatoxin on montmorillonite modified by low-molecular-weight
      humic acids].
AB  - The adsorption of a typical biogenic toxin aflatoxin B1 on montmorillonite
      modified by low-molecular-weight humic acids (M(r) < 3 500) was investigated. The
      montmorillonite rapidly adsorbed the aflatoxin B1 until amounting to the maximal
      capacity, and then the adsorbed aflatoxin B1 slowly released into solution and
      reached the sorption equilibrium state after 12 h. The sorption isotherm of
      aflatoxin B1 by montmorillonite could be well described by Langmiur model, while
      the sorption isotherm by humic acid-modified montmorillonite was well fitted by
      using the Freundlich model. The modification of the montmorillonite with humic
      acids obviously enhanced its adsorption capacity for aflatoxin B1, and the
      amounts of aflatoxin adsorbed by modified montmorillonite were obviously higher
      than those by montmorillonite. The sorption enhancement by humic acid
      modification was attributed to (1) the enlarged adsorption sites which owed to
      the surface collapse of crystal layers induced by organic acids, and (2) the
      binding of aflatoxin with the humic acid sorbed on mineral surface. In addition,
      the adsorption amounts of aflatoxin by montmorillonite and modified
      montmorillonite increased with the increase of pH values in solution, and more
      significant enhancement was observed for the latter than the former, which
      attributed to the release of humic acids from the modified montmorillonite with
      the high pH values in solution. This indicates that increasing the pH values
      resulted in the enhanced hydrophilic property and the release of the organic
      acids presented in modified montmorillonite, and more sorption sites were
      available for aflatoxin on the modified montmorillonite. Results of this work
      would strengthen our understanding of the behavior and fate of biological
      contaminants in the environment.

PMID- 22624395
TI  - [Influence of operating parameters on surfactant-enhanced washing to remedy PAHs
      contaminated soil].
AB  - Liquid/solid ratio (L/S) is an important influencing factor on contaminant
      removal in soil washing. The impact of different liquid/solid ratio on washing
      performance with Triton X-100 and Tween-80 was studied respectively and evaluated
      through removal ratio (R), surfactant adsorption loss ratio (V(s)) and
      solubilization percent (SP). The results presented that the performance of
      washing to remove PAHs in soil was significantly affected by liquid/solid ratio.
      PAH removal ratio was gradually increased with liquid/solid ratio increasing in
      the non-linear form, R presented nonlinear increasing until L/S = 10: 1.
      Surfactant adsorption loss ratio was insignificantly decreased. At the same
      liquid/solid ratio, removal ratio of Triton X-100 is more than that of Tween-80.
      V(s) presented drastic decreasing until L/S = 10: 1, adsorption loss ratio of
      Triton X-100 is less than that of Tween-80. SP was decreased after maximum value
      is occurred at L/S = 10: 1. Combining with R, V(s) and SP, L/S = 10:1 should be
      an effective washing point, Triton X-100 should be a reasonable washing solution
      and SP is a more effective index to chose liquid/solid ratio. When Triton X-100
      is as washing solution and L/S = 10: 1, R, V(s) and SP is 74.7%, 23.47% and
      48.99%, respectively.

PMID- 22624396
TI  - [Study on the land use optimization based on PPI].
AB  - Land use type and managing method which is greatly influenced by human
      activities, is one of the most important factors of non-point pollution. Based on
      the collection and analysis of non-point pollution control methods and the
      concept of the three ecological fronts, 9 land use optimized scenarios were
      designed according to rationality analysis of the current land use situation in
      the 3 typed small watersheds in Miyun reservoir basin. Take Caojialu watershed
      for example to analyze and compare the influence to environment of different
      scenarios based on potential pollution index (PPI) and river section potential
      pollution index (R-PPI) and the best combination scenario was found. Land use
      scenario designing and comparison on basis of PPI and R-PPI could help to find
      the best combination scenario of land use type and managing method, to optimize
      space distribution and managing methods of land use in basin, to reduce soil
      erosion and to provide powerful support to formulation of land use planning and
      pollution control project.

PMID- 22624397
TI  - [Research on algal diversity in Zoige Alpine Wetland].
AB  - Water samples were collected in summer and winter in Zoige Alpine Wetland. Both
      the traditional cultivable and microscopic method and modern molecular approach
      were used to reveal the algal diversity in the wetland. For the samples collected
      in summer, single-cell Chlorophyta was cultured, isolated and identified. The
      results showed that there were at least four kinds of Chlorophyta, which were
      Chlorella vulgaris Beij., Planktosphaeria gelatinosa G. M. Smith, Scenedesmus
      abundans Kirchne and Scenedesmus bijuga Turp. They all belonged to
      Chlorococcales. The dominant species was Chlorella vulgaris Beij., which had been
      purified. For the samples collected in winter, the microscopic results showed
      that the dominant populations were diatoms, which is in accordance with the
      principle that the dominant populations of algae are diatoms in low-temperature
      seasons. Cyanobacterial 16S rRNA gene clone library showed that the dominant
      group was Bacillaripiophyta (35.3%). And Cyanobacteria contained the orders of
      Chroococcales (5.9%), Nostocales (11.8%), Osillatoriales (11.8%) and Unclassified
      Cyanobacteria (35.3%). There were some clones related to those from frigid
      habitats, such as Leptolyngbya-related clones.

PMID- 22624398
TI  - [Effects of three fungicides on arbuscular mycorrhizal fungal infection and
      growth of Scutellaria baicalensis Georgi].
AB  - To make full use of arbuscular mycorrhizal (AM) fungal resources to increase the
      quantity and quality of Chinese medicinal materials and reduce the use of
      fungicide and environmental pollution, this research was carried out under pot
      culture condition to study the effects of benomyl, difenconazole and flusilazol
      on AM fungal (Glomus mosseae) colonization and the growth of Scutellaria
      baicalensis. The results showed that Glomus mosseae generally promoted the growth
      of host plant under the same fungicide application, and the effect of Glomus
      mosseae was different with different fungicides. The growth of non-mycorrhizal
      Scutellaria baicalensis was inhibited by applying with different fungicides. On
      mycorrhizal plants, contents of K in shoot and Fe in root significantly decreased
      under benomyl treatment; the contents of total N, K in shoot, Baicalin and Ca in
      root significantly decreased under difenconazole treatment; mycorrhizal
      colonization, the contents of total P, Baicalin, K and Cu in shoot, total N, Ca,
      Zn and Fe in root significantly decreased under flusilazol. The inhibitory
      effects of flusilazol on the Glomus mosseae colonization and growth of
      Scustellaria baicalensis were greater than those of difenconazole and benomyl. It
      is reasonable to choose less toxic fungicides in Scutellaria baicalensis
      cultivation to reduce the harmful effects on arbuscular mycorrhizal fungi.

PMID- 22624399
TI  - [Community structure and spatial distribution of anaerobic ammonium oxidation
      bacteria in the sediments of Chongming eastern tidal flat in summer].
AB  - The objectives of this study were to identify whether there were Anaerobic
      Ammonium Oxidation (ANAMMOX) bacteria in the surface sediments of Chongming
      eastern tidal flat in the Yangtze estuary and the feature of their community
      structure and spatial distribution. Based on the total DNA extracted from the
      surface sediments of Chongming eastern tidal flat, ANAMMOX-specific 16S rDNA
      fragments were amplified. PCR products were cloned and sequenced, and an ANAMMOX
      specific 16S rDNA gene library was established. Phylogenetic tree was constructed
      using MEGA5 after the sequences were checked in the GenBank database.
      Phylogenetic analysis indicated that the clone sequences CM-L-7 and CM-L-18 had
      98% identities with ANAMMOX bacteria Candidatus 'Scalindua sp.'. CM-L-13 had 94%
      identities with Candidatus 'Scalindua wagneri'. CM-M-6 had 94% identities with
      Candidatus 'Kuenenia sp.'. CM-M-22 had 95% identities with Anaerobic ammonium
      oxidizing planctomycete JMK-1. CM-H-15 had 94% identities with Candidatus
      'Kuenenia stuttgartiensis'. The results indicated that there were ANAMMOX
      bacteria in the surface sediments of Chongming eastern tidal flat, but the
      ANAMMOX species were diverse in different tidal flats: Candidatus 'Scalindua' was
      the predominant group in the low tidal flat, while Candidatus 'Kuenenia' was the
      major population in the high tidal flat and the middle tidal flat. In comparison
      with the high and low tidal flats, the community structure of ANAMMOX bacteria in
      the middle tidal flat was the most complicated. A portion of the sequences
      related to uncultivated bacteria outside the known ANAMMOX cluster, probably
      indicated that there were potential ANAMMOX bacteria in the sediments of
      Chongming eastern tidal flat.

PMID- 22624400
TI  - [Microbial degradation of 2, 2', 4, 4'-tetrabrominated diphenyl ether under
      anaerobic condition].
AB  - Polybrominated diphenyl ethers are emerging contaminants in the environment,
      among which 2, 2' 4, 4'-tetrabrominated diphenyl ether (BDE-47) is one of the
      most frequently detected and the most toxic to organisms. Using BDE-47 as the
      object, this study investigated the degradation of BDE-47 by six enriched
      cultures containing Dehalococcoides species. The purpose is to understand the
      microbial degradation of BDE-47 under anaerobic condition and its kinetics. Serum
      bottles of 100 mL were used to construct the microcosms and enrich the anaerobic
      microorganisms. For each culture, two treatments were performed. One used BDE-47
      as the only energy source with the designed concentration of 200 microg x L(-1),
      and the other used both BDE-47 and trichloroethene (TCE) as the energy source
      with the designed concentrations being 200 microg x L(-1) and 13 mg x L(-1),
      respectively. After three months of experiment, two enriched cultures (6M6B and
      T2) could obviously degrade BDE-47, producing BDE-17 and BDE-4 (and small amount
      of DE). The presence of TCE inhibited the degradation of BDE-47 by 6M6B and T2
      cultures to a certain degree. The PCR-DGGE assay was performed to compare the
      microbial community structure of various enrichments and it was found that
      Acetobacterium sp. had good correlation with the degradation of BDE-47. Under
      three different initial BDE-47 concentrations (50 microg x L(-1), 250 microg x L(
      1) and 500 microg x L(-1)), the degradation rates of BDE-47 were 0.003 3, 0.001 4
      and 0.001 0 d(-1), respectively. This study demonstrated that BDE-47 could be
      reductively degraded by bacteria under anaerobic condition, producing BDE-17 and
      BDE-4. Acetobacterium sp. might play an important role in the degradation of BDE
      47. High concentration of BDE-47 might inhibit the activity of the BDE-47
      degrading bacteria to a certain degree.

PMID- 22624401
TI  - [Effect of heavy metals on degradation of BDE-209 by white-rot fungus].
AB  - Effects and mechanisms of heavy metals Cu, Cd and Pb on the growth of white-rot
      fungus P. chrysosporium and its ability of BDE-209 degradation were studied. The
      results showed that low concentrations of heavy metals (< or = 1 mg x L(-1))
      stimulated the growth of P. chrysosporium with the order of Cd > Pb > Cu when 1
      mg x L(-1) of each heavy metal was concerned, while high concentrations (> 1 mg x
      L(-1)) depressed it. P. chrysosporium degraded BDE-209 efficiently with
      degradation efficiency reaching 69.7% after 7 days. The presence of heavy metals
      significantly influenced the capability of P. chrysosporium to decompose BDE-209
      (P < 0.05). Low concentrations of Cu (< or = 1 mg x L(-1)) and Cd (< or = 0.5 mg
      x L(-1)) accelerated the degradation of BDE-209 and the degradation efficiency
      was enhanced from 69.7% to 84.4% when 1 mg x L(-1) Cu was present, while Pb had
      negative effect. On the other hand, all three metals under high concentrations (>
      1 mg x L(-1)) showed depressed effects on the degradation in the order of Cd > Pb
      > Cu. The growth of P. chrysosporium did not completely positively correlate with
      the degradation capability of BDE-209. The degradation of BDE-209 by P.
      chrysosporium conformed to the first-order kinetic model. The reaction rate
      constant k raised firstly and then declined with increasing concentrations of Cu
      and Cd, and the highest k of 0.321 2 achieved in the presence of 1 mg x L(-1) Cu.
      By contrast, the constant k declined all the way when Pb existed. A further
      investigation into the effects of heavy metals on degradation of BDE-209 by
      extracellular enzymes derived from P. chrysosporium was conducted, and the
      distance correlation analysis of the degradation by extracellular enzymes and the
      whole cell was carried out. The results demonstrated that the degradation by
      extracellular enzymes and the whole cell was 63.7%, 69.7% separately, showing no
      significant difference of degradation capability between them, which proved that
      the extracellular enzymes played dominating role in the degradation of BDE-209.
      Furthermore, the distance correlation coefficient R were all greater than 0.9
      when three heavy metals existed, certificating that heavy metals affected the
      degradation of BDE-209 through the interaction between extracellular enzymes and
      heavy metals.

PMID- 22624402
TI  - [Biodegradation mechanism of DDT and chlorpyrifos using molecular simulation].
AB  - In order to explore the microscopic degradation mechanism of organic pesticides
      degrading enzymes, we used molecular docking method to investigate the binding
      modes of DDT to laccase and chlorpyrifos to organophosphorus hydrolase, and
      obtained the corresponding complex structures. According to the principle of
      minimum scoring, the results showed that the MolDock scores were -103.134 and 
      111.626, re-rank scores were -72.858 and -80.261, respectively. And we used
      LPC/CSU server search the interactions between organic pesticides and their
      degrading enzymes. Our results showed that hydrophobic interaction was the
      strongest contacts in DDT-laccase complex, and both hydrogen bonds and
      hydrophobic interactions were the strongest contacts when chlorpyrifos
      organophosphorus hydrolase complex. The amino acid residues Tyr224 in laccase and
      Arg254 in organophosphorus hydrolase were detected to play significant roles in
      catalytic processes.

PMID- 22624403
TI  - [Construction of a microbial consortium RXS with high degradation ability for
      cassava residues and studies on its fermentative characteristics].
AB  - A microbial consortium with high effective and stable cellulosic degradation
      ability was constructed by successive enrichment and incubation in a peptone
      cellulose medium using cassava residues and filter paper as carbon sources, where
      the inoculums were sampled from the environment filled with rotten
      lignocellulosic materials. The degradation ability to different cellulosic
      materials and change of main parameters during the degradation process of cassava
      residues by this consortium was investigated in this study. It was found that,
      this consortium can efficiently degrade filter paper, absorbent cotton, avicael,
      wheat-straw and cassava residues. During the degradation process of cassava
      residues, the key hydrolytic enzymes including cellulase, hemicellulase and
      pectinase showed a maximum enzyme activity of 34.4, 90.5 and 15.8 U on the second
      or third day, respectively. After 10 days' fermentation, the degradation ratio of
      cellulose, hemicellulose and lignin of cassava residues was 79.8%, 85.9% and
      19.4% respectively, meanwhile the loss ratio of cassava residues reached 61.5%.
      Otherwise,it was found that the dominant metabolites are acetic acid, butyric
      acid, caproic acid and glycerol, and the highest hydrolysis ratio is obtained on
      the second day by monitoring SCOD, total volatile fatty acids and total sugars.
      The above results revealed that this consortium can effectively hydrolyze cassava
      residues (the waste produced during the cassava based bioethanol production) and
      has great potential to be utilized for the pretreatment of cassava residues for
      biogas fermentation.

PMID- 22624404
TI  - [Anaerobic digestion of animal manure contaminated by tetracyclines].
AB  - Anaerobic digestion of pig manure spiked with tetracycline (TC) and
      chlortetracycline (CTC) and the degradation of the two antibiotics during the
      anaerobic digestion at 35 degrees C were investigated. The results indicate that
      propionate was the main volatile fatty acid produced during the anaerobic
      digestion followed by acetate. Compared with the CTC addition, TC + CTC addition
      showed obvious inhibitory effect on the hydrolysis and acidification of easily
      digestible organic components of pig manure. The cumulative methane production of
      TC, CTC, TC + CTC and CK2 during anaerobic digestion was 386.4 mL, 406.0 mL,
      412.1 mL and 464.6 mL, respectively. Degradation of TC and CTC followed the first
      order kinetic equation. The half-life of TC and CTC was 14-18 days and 10 days,
      respectively. After the treatment of 45-day anaerobic digestion, the degradation
      efficiency of TC was 88.6%-91.6% with 97.7%-98.2% of CTC. Therefore, anaerobic
      digestion shows the benefit on the management of animal manures contaminated by
      tetracyclines.

PMID- 22624405
TI  - [Continuous dry fermentation of pig manure using up plug-flow type anaerobic
      reactor].
AB  - To solve the problems of ammonia inhibition and discharging difficulty in
      continuous dry fermentation of pig manure, under the experimental conditions of
      temperature of (25 +/- 2) degrees C and organic loading rate (TS) of 4.44 g x (L
      x d) (-1), a lab-scale up plug-flow type anaerobic reactor (UPAR) was setup to
      investigate biogas production, ammonia inhibition, effluent liquidity, and the
      feasibility of continuous dry fermentation of pig manure using up plug-flow type
      anaerobic reactor. The experiment was operated for 160 days using the pig manure
      with four different TS mass fractions (20%, 25%, 30%, 35%) as feeding. Results
      showed that the feeding TS mass fraction exerted a significant influence on the
      dry fermentation of pig manure; the stable volumetric biogas production rates of
      four different feeding TS mass fractions were 2.40, 1.73, 0.89, and 0.62 L x (L x
      d)(-1), respectively; the biogas producing efficiencies of the reactors with
      feeding TS mass fractions of 20%, 25% and 30% were obviously superior to that
      with feeding TS of 35%. With feeding TS mass fraction increased from 20% to 35%,
      obvious inhibition to biogas producing occurred when concentration of ammonia
      nitrogen reached more than 2 300 mg x L(-1). When the feeding TS mass fraction
      was 35%, the concentration of ammonia nitrogen could accumulate to 3 800 mg x L(
      1) but biogas production rate decreased 74.1% of that with feeding TS of 20%.
      Additionally, while the feeding TS mass fraction was 35%, the effluent TS mass
      fraction achieved 17.1%, and the velocity of effluent was less than 0.002 m x s(
      1) the effluent of UPAR could not be smoothly discharged.

PMID- 22624407
TI  - Time trend and clinical pattern of extrapulmonary tuberculosis in Serbia, 1993
      2007.
AB  - BACKGROUND/AIM: Increased incidence of extrapulmonary tuberculosis (XPTB) is
      reported worldwide. Serbia is a country in socio-economic transition period with
      low-middle HIV prevalence and intermediate-to-low tuberculosis (TB) incidence
      rate, 100% directly observed treatment (DOT) coverage, and mandatory BCGC
      vaccination at birth. The aim of the study was to examine the incidence trend and
      clinical features of XPTB in Serbia during a 15-year period. METHODS: This
      retrospective observational study included XPTB cases diagnosed in the period
      between 1st January 1993 and 31st Decembre 2007, according to the reports of the
      National Referral Institute of Lung Diseases and Tuberculosis in Belgrade and
      Central Tuberculosis Register. Population estimates with extrapolations were
      based on 1991 and 2002 census data. RESULTS: While the overall TB incidence rate
      showed a slight, not significant decreasing trend (p = 0.535), a significant
      increase was found for XPTB (y = 1.7996 + 0.089x; R2 = 0.4141; p = 0.01). A total
      of 2,858 XPTB cases (newly diagnosed and 10% relapses) gave an average age
      specific incidence rate of 2.51/100,000 population (95% confidence interval, SD =
      0.6182) with 8.9% annual increase. The male-to-female ratio was 0.54. Lymph nodes
      were most frequently affected site (48.5%) followed by genitourinary (20.5%),
      pleural (12%), and osseo-arthicular (10.3%) TB. Treatment outcome was successful
      in 88.29% of patients (cured and completed), 3.64% died, 5.18% interrupted, 0.57%
      displaced, and 2.3% unknown. CONCLUSION: Increasing trend of XPTB incidence rate
      may be a result of increased morbidity due to still present risk factors,
      possible higher detection rate in Serbia and better notification. A high coverage
      of newborns with BCG vaccination at birth might contribute to a decreased number
      and rare XPTB cases in children.

PMID- 22624408
TI  - Transforming growth factor beta1, matrix-metalloproteinase-2 and its tissue
      inhibitor in patients with pseudoexfoliation glaucoma/syndrome.
AB  - BACKGROUND/AIM: Transforming growth factor-beta1 (TGF-beta1), oxidative stress
      and imbalance between matrix metalloproteinases (MMPs) and their tissue
      inhibitors (TIMPs) may play an important role in pathogenesis of
      pseudoexfoliation syndrome/glaucoma (PEX Sy/Gl). The aim of the study was to
      measure concentrations of TGF-beta1, MMP-2, TIMP-2 in the aqueous humor in the
      examined group, as well as to compare the biochemical findings with the following
      clinical parameters: degree of chamber angle pigmantation, presence of
      pseudoexfoliation and the value of intraocular pressure (IOP). METHODS: Aqueous
      samples from 30 patients with cataract, 30 patients with PEX Sy, 36 patients with
      PEX Gl, and 42 patients with primary open-angle glaucoma (POAG) were collected
      during phacoemulsification cataract surgery. TGF beta1, MMP-2, TIMP-2 Fluotokine
      Multi Analyze Profiling kits and Luminex technology were used to simultaneously
      measure TGF beta1, MMP-2 and TIMP-2. RESULTS: TGF-beta1, MMP-2, TIMP-2 were
      detected in human aqueous from all the groups with the highest level in the group
      with PEX Gl. Statistically, a significant correlation between the levels of TGF
      beta1, MMP-2, TIMP-2 in the aqueous humor of the patients with PEX Gl and the IOP
      value was confirmed (p < 0.05). In this group, the positive correlations between
      the TGF beta1 concentration in the aqueous humor and the presence of
      pseudoexfoliation (p < 0.01), on the one hand, and between the TIMP-2 level and
      the presence of pseudoexfoliation (p < 0.05), on the other, were reported. A
      statistically significant positive correlation of TGF-beta1 and MMP-2, and the
      degree of chamber angle pigmentation in the PEX Gl group was confirmed (p <
      0.05). In the POAG group, TIMP-2 values were in a negative correlation with the
      degree of pigmentation (p < 0.05), and the IOP value (p < 0.05). CONCLUSION: TGF
      beta1 and MMP-2 affect the degree of chamber angle pigmentation and the degree of
      pseudoexfoliation in patients with pseudoexfoliative glaucoma.

PMID- 22624409
TI  - Effects of a short-term differently dosed aerobic exercise on maximum aerobic
      capacity in breast cancer survivors: a pilot study.
AB  - BACKGROUND/AIM: Regular physical activity and exercise improves quality of life
      and possibly reduces risk of disease relapse and prolongs survival in breast
      cancer survivors. The aim of this study was to evaluate the impact of a 3-week
      moderate intensity aerobic training, on aerobic capacity (VO2max) in breast
      cancer survivors. METHODS: A prospective, randomized clinical study included 18
      female breast cancer survivors in stage I-IIIA, in which the primary treatment
      was accomplished at least 3 months before the study inclusion. In all the
      patients VO2max was estimated using the Astrand's protocol on a bicycle-ergometer
      (before and after 3 weeks of training), while subjective assessment of exertion
      during training were estimated by the Category-Ratio RPE Scale. Each workout
      lasted 21 minutes: 3 minutes for warm-up and cool-down each and 15 min of full
      training, 2 times a week. The workload in the group E1 was predefined at the
      level of 45% to 65% of individual VO2max, and in the group E2 it was based on
      subjective evaluation of exertion, at the level marked 4-6. Data on the
      subjective feeling of exertion were collected after each training course in both
      groups. RESULTS: We recorded a statistically significant improvement in VO2max in
      both groups (E1--11.86%; E2--17.72%), with no significant differences between the
      groups. The workload level, determined by the percent of VO2max, was different
      between the groups E1 and E2 (50.47 +/- 7.02% vs 55.58 +/- 9.58%), as well as
      subjective perception of exertion (in the groups E1 and E2, 11.6% and 41.6% of
      training, respectively, was graded in the mark 6). CONCLUSION: In our group of
      breast cancer survivors, a 3-week moderate intensity aerobic training
      significantly improved the level of VO2max.

PMID- 22624410
TI  - Vitamin D and parathyroid hormone in relation to bone mineral density in
      postmenopausal women.
AB  - BACKGROUND/AIM: Despite vitamin D insufficiency being widely reported, in Serbia
      the epidemiological data lack information regarding vitamin D status in the sera
      of postmenopausal women. The aim of this study was to establish the prevalence of
      inadequate serum 25-hydroxyvitamin D [25(OH)D] concentrations in postmenopausal
      Serbian women with seasonal variations of 25(OH)D, in relation to parathyroid
      hormone (PTH) and bone mineral density (BMD). METHODS: A total of 95
      postmenopausal women, mean age 65.1 +/- 9.08 years, were examined. Measurements
      of 25(OH)D and PTH were performed both in the winter and the summer period, using
      electrochemiluminiscence immunoassays. BMD (g/cm2) was measured by the dual
      energy x-Ray absortimetry (DXA) method on the spine and hip areas. RESULTS: A
      decreased value of vitamin D (< 75 nmol/L) in 88.4% of postmenopausal women and
      an elevated level of PTH (> 65 pg/mL) in 25.3% of the cases were found. Elevated
      PTH varied individually, but was mostly increased if 25(OH)D was equal or lower
      than 37.6 nmol/L. 25(OH)D insufficiency was found in winter in 94.5% and in
      summer in 80% of the cases (p < 0.01). The mean of the PTH was higher (p < 0.05)
      in winter than in summer. A significant negative correlation between 25(OH)D and
      PTH (p < 0.001) was proved. Correlation between 25(OH)D and PTH with BMD at
      lumbar spine was established in the whole group, but at the femoral neck in women
      aged over 65 years (p < 0.05). CONCLUSION: Our results showed a high prevalence
      of vitamin D insufficiency (88.4%) among postmenopausal women. The levels of
      25(OH)D and PTH changed significantly according to the season.

PMID- 22624411
TI  - Evaluation of the patients with Grave's ophthalmopathy after the corticosteroids
      treatment.
AB  - BACKGROUND/AIM: Graves' ophthalmopthy is one of the most common causes of
      exophthalmos as well as the most common manifestation of Graves' disease. The
      treatment of Graves' ophthalmopathy includes ophthalmological and
      endocrinological therapy. The aim of this study was to clinically evaluate the
      patients with Graves' ophthalmopathy treated with corticosteroids. METHODS:
      Evaluation of 21 patients was performed in the Ophthalmology Clinic and
      Endocrinology Clinic, Clinical Centre Kragujevac, in the period from 2009 to
      2010. They were treated with pulse doses of intravenous corticosteroids. They
      were referred to ophthalmologist by endocrinologist in euthyroid condition in the
      active phase of Graves' ophthalmopathy (ultrasonography of orbit findings and
      positive findings of antithyroid stimulating hormone receptor antibody--anti-TSH
      R Ab). The clinical activity score (CAS) and NO SPECS classification for
      evaluation of disease severity were used. Ophthalmological examination includes:
      best corrected visual acuity, slit-lamp exam, Hertels' test, direct
      ophthalmoscopy and ultrasonography of the orbit. RESULTS: According to our
      results 76.19% of the patients were female; mean age of the patients was 35.2 +/-
      5.6 years. According to CAS classification after 6 months of the treatment
      recovery was shown in 23.81% of the patients, partial amelioration in 47.62% and
      no clinical amelioration in 28.57% of the patients. We achieved better results
      with male, young patients with high clinical activity score. Good results were
      observed after the first dose of corticosteroids, much better CAS after the third
      dose, which maintained until 6 months after the first treatment. CONCLUSION: Our
      results signify that intravenous pulse dose of corticosteroids treatment of the
      patients with Graves' ophthalmopthy is safe, comfortable, clinically justified
      and accessible for the clinicians and patients. Positive results are achieved
      after the first dose with increasing trend up to the third dose, which was
      maintained for the next three months.

PMID- 22624413
TI  - Quality of life in childhood and adolescence: from concept to practice.

PMID- 22624412
TI  - Urodynamic characteristics of the modified orthotopic ileal neobladder.
AB  - BACKGROUND/AIM: Radical cystectomy is the method of choice in management of
      muscle invasive, organ-confined tumors of the bladder (T2-T4, N0-Nx). The most
      frequent continent orthotopic urinary diversion after radical cystectomy is the
      ileal neobladder. A modified technique consists of using a shorter segment of the
      terminal ileum than the standard technique, around 30 cm. The aim of this study
      was to determine the urodynamic characteristics of the orthotopic ileal
      neobladder created by a modified technique. METHODS: In this prospective clinical
      study we analyzed the urodynamic parameters of 24 patients who had underwent
      radical cystectomy with orthotopic urinary diversion by ileal neobladder created
      using a modified technique. In all the patients we performed invasive and
      noninvasive urodynamic investigations 12 months after the operation. The urethral
      pressure profile parameters analyzed were maximal urethral pressure, maximal
      urethral closure pressure and the functional urethral profile length. RESULTS:
      The average age of the patients was 63 (49-73) years, 90% were males and 10% were
      females. The median length of the shorter segment of the terminal ileum was 28
      (range 22-35) cm. Prior to enterocystometry and uroflowmetry postvoid residual
      (PVR) urine was measured by a urethral catheter. The median PVR was 16.7 (0-140)
      mL. The median enterocystometric capacity was 396 (range 372-532) mL. The median
      end filling pouch pressure was 27.6 (range 20-70) cmH2O. The median maximal flow
      of urine was 22.1 (range 9.7-39.5) mL/s and the average flow of urine was 9.61
      (range 3.6-17.6) mL/s. Flow time in the analyzed group was 47.5 (range 22-119) s.
      The median maximal urethral pressure was 54 (range 12-101) cmH2O, maximal
      urethral closure pressure 36.6 (range 6-91) cmH2O. Functional urethral profile
      length was 14.9 (range 4-37) mm. CONCLUSION: An ileal orthotopic pouch created by
      a modified technique using a shorter segment of the terminal ileum after 12
      months presents with urodynamic characteristics similar to the native bladder.

PMID- 22624414
TI  - Conceptual framework for communicating health and illness across cultures.

PMID- 22624415
TI  - [Major changes in the European Resuscitation Council Guidelines for
      Cardiopulmonary Resuscitation 2010 in the field of adult basic and advanced life
      support].

PMID- 22624416
TI  - [Impact of heart myxoma localization upon its clinical course and outcome].
AB  - INTRODUCTION: Primary heart tumors are very rare. They can be benign and
      malignant. Benign ones make about two thirds of all heart tumors. However, they
      are benign only by their biologic characteristics, but potentially malignant by
      their localization. About three forths of benign tumors are myxomas. Their growth
      is usually slow and they can be for a long time silent, particularly if they do
      not compromise vital functional parts of the heart. Myxomas grow in the atria,
      mostly in the left one and very rarely in the ventricles. CASE REPORT: We
      presented two patients with myxomas in the left, and, in the right atrium which
      are representative samples of the most common localization of heart myxoma
      considering previous knowledge of these tumors. Analysis of the clinical course
      in the two presented patients with characteristic localizations showed general
      characteristics of the clinical course of heart myxoma. The patients did not have
      characteristic symptoms for a rather long period of time and the findings
      obtained by standard examinations did not raise suspicion of heart tumor.
      Pulmonary symptomatology in one patient and cardial in the other, when tumor had
      already occupied almost the entire atrium, suggested necessity of cardiologic
      examination. Indication for operation was in both patients confirmed after
      performed echocardiography, computed tomography of the thorax and angiography
      with ventriculography. The size of the removed atrial tumors and their
      localization explained some of the patients' troubles, but it was also amazing
      that they had not caused more serious problems. Operation as the only method of
      treatment was successful in both female patients and its effect was permanent. At
      annual controls neither recurrence of the tumor nor troubles possibly associated
      with it were observed. CONCLUSION: Patients with heart myxoma usually pass
      through asymptomatic or oligosymptomatic phase, but when troubles become
      manifested, they do not much differ from those due to other causes. For this
      reason this tumor can be diagnosed just when complications caused by its
      localization and growth develop. Modern cardiologic diagnostics, primarily
      preventive non-invasive echocardiography, enables timely diagnosis and removal of
      the tumor because only then it may take a name benign tumor.

PMID- 22624417
TI  - Intracranial yolk sac tumor in an adult patient: MRI, diffusion-weighted imaging
      and 1H MR spectroscopy features.
AB  - INTRODUCTION: Yolk sac tumors represent only 5%-7% of intracranial germ cell
      tumors, which comprise about 1% of all primary brain tumors in adults. Literature
      data about nonspecific imaging characteristics of these tumors are scant. We
      presented magnetic resonance imaging findings with diffusion-weighted imaging and
      proton magnetic resonance spectroscopy of this rare type of tumor in an adult
      patient. CASE REPORT: A 55-year-old man with progressive left side weakness,
      headache, dizziness and ataxia, underwent preoperative magnetic resonance
      imaging, diffusion-weighted imaging and proton magnetic resonance spectroscopy.
      After surgical resection and histological analysis, the final diagnosis of yolk
      sac tumor was established. Retrospective imaging analysis were performed in order
      to determine imaging and biochemical parameters that could be useful in the
      diagnostic evaluation of this tumor type. CONCLUSION: Though the imaging features
      of yolk sac tumor are not specific, morphoanatomical and metabolic imaging could
      offer the information that provides new insights into this tumor that may
      facilitate further therapeutic decision process and potentially provides better
      information regarding the disease prognosis.

PMID- 22624418
TI  - [Elective visceral hybrid repair of type III thoracoabdominal aortic aneurysm].
AB  - INTRODUCTION: According to the classification given by Crawford et al. type III
      thoracoabdominal aortic aneurysm (TAAA) is dilatation of the aorta from the level
      of the rib 6 to the separation of the aorta below the renal arteries, capturing
      all the visceral branch of aorta. Visceral hybrid reconstruction of TAAA is a
      procedure developed in recent years in the world, which involves a combination of
      conventional, open and endovascular aortic reconstruction surgery at the level of
      separation of the left subclavian artery to the level of visceral branches of
      aorta. CASE REPORT: We presented a 75-years-old man, with elective visceral
      hybrid reconstruc tion of type III TAAA. Computerized scanning (CT) angiography
      of the patient showed type III TAAA with the maximum transverse diameter of
      aneurysm of 92 mm. Aneurysm started at the level of the sixth rib, and the end of
      the aneurysm was 1 cm distal to the level of renal arteries. Aneurysm compressed
      the esophagus, causing the patient difficulty in swallowing act, especially solid
      food, and frequent back pain. From the other comorbidity, the patient had been
      treated for a long time, due to chronic obstructive pulmonary disease and
      hypertension. In general endotracheal anesthesia with epidural analgesia, the
      patient underwent visceral hybrid reconstruction of TAAA, which combines classic,
      open vascular surgery and endovascular procedures. Classic vascular surgery is
      visceral reconstruction using by-pass procedure from the distal, normal aorta to
      all visceral branches: celiac trunk, superior mesenteric artery and both renal
      arteries, with ligature of all arteries very close to the aorta. After that, by
      synchronous endovascular technique a complete aneurysmal exclusion of
      thoracoabdominal aneurysm with thoracic stent-graft was performed. The
      postoperative course was conducted properly and the patient left the Clinic for
      Vascular Surgery on postoperative day 21. Control CT, performed 3 months after
      the surgery showed that the patient's vascular status was uneventful with
      functional visceral by-pass and with good position of a stent-graft without a
      significant endoleak. CONCLUSION: Visceral hybrid reconstruction represents a
      complementary surgical technique to that with open reconstruction of TAAA. This
      approach is far less traumatic to a patient, and is especially important in
      patients with lot of comorbidities, because there is no need for thoracotomy, and
      ischemic-reperfusion injury of the body is reduced to a minimum.

PMID- 22624419
TI  - Unilateral optic nerve aplasia associated with microphthalmos.
AB  - INTRODUCTION: Optic nerve aplasia is a rare developmental anomaly characterised
      by the congenital absence of the optic nerve, central retinal vessels and retinal
      ganglion cells that is seen most often in a unilaterally malformed eye. CASE
      REPORT: We reported a girl with a very rare anomaly of the eye, unilateral
      aplasia of the optic nerve and microphthalmia. We carried out a complete
      ophthalmological examination, A- and B-scan ultrasonography, magnetic resonance
      imaging (MRI) of the orbit and brain, pediatrician, neurological examinations and
      karyotype determination. The examined child was a third child from the third
      regular pregnancy, born at term (39 GS, BM 3100 g). Family ocular history was
      negative. The right corneal diameter was 7.5 mm and left 10 mm. On dilated fundus
      examination, the right eye showed the absence of op tic nerve and central retinal
      vessels. B-scan echography showed a small right globe (axial length 13.80 mm),
      normal size left globe (axial length 18.30 mm) and the absence of optic nerve on
      the right eye. Physical and neurological findings and karyotype was normal. MRI
      of the orbits and brain marked asymmetry of globe size and unilateral absence of
      the optic nerve. The patient is under the control of a competent ophthalmologist
      and prosthetic. CONCLUSION: Further aesthetic and functional development of a
      young person is the primary goal in tracking this rare congenital optic nerve
      anomalies in the malformed eye.

PMID- 22624420
TI  - [Success rate of intrauterine insemination in patients with unknown infertility].
AB  - BACKGROUND/AIM: Unknown cause of infertility exists in 10%-26% of couples with
      infertility problems. Treatment of these couples depends on the posibility of
      correcting the unidentified defect over time. Intrauterine insemination (IUI) and
      ovaluation stimulation are methods of choice in treatment of unexplained
      fertility, but if a woman is older than 37 years, in vitro fertilization (IVF)
      could be directly recommended. The aim of this research was to compare the
      success rate of pregnancies with IUI between the patients with unexplained
      infertility and the patients with mild form endometriosis. METHODS: The study
      included on 50 patients diagnosed with mild form endometriosis (group A) and 50
      patients with unknown cause infertility (group B). Using the same therapeutical
      protocol, human menopausal gonadothropin (hMG) stimulation and horionic
      gonadropin (hCG) induction were applied, as well as IUI. RESULTS: The percentage
      of achieved ovulation was higher in the group B (p < 0.05). During the 3
      simulated sequential periods 102 IUI were performed in the group A and 97 IUI in
      the group B. In the group A there were 6 single and 1 twin pregnancies sucesfully
      conceived (14%), while in group B there were 9 (18%) single pregnancies.
      CONCLUSION: The use of a combination of controled ovarian hyperstimulation and
      IUI is an effective, cheap and safe method for treating infertility couples,
      especially couples with unknown cause infertility. Mild form endometriosis, as
      etiological infertility factor, has a negative impact on IUI success rate.

PMID- 22624421
TI  - Factors influencing the choice of antidepressants: a study of antidepressant
      prescribing practice at University Psychiatric Clinic in Belgrade.
AB  - BACKGROUND/AIM: Antidepressants are a widely used class of drugs. The aim of this
      study was to investigate different aspects of antidepressant prescribing practice
      at University Psychiatric Clinic in Belgrade. METHODS: This cross-sectional study
      was carried out by retrospective analysis of the patient's medical charts. The
      study included all patients with antidepressant prescribed at discharge during
      2009 (n = 296). The evaluation was focused on patient-related factors (socio
      demographic and illness related), psychiatrist-related factors (sex and duration
      of working experience) and drug related factors (type of antidepressant, dose,
      polypharmacy and reimbursement by national health insurance). RESULTS:
      Antidepressants were prescribed for unipolar depression (F32-34, ICD X) either
      without comorbidity (46.2%) or with comorbidity (24.7%), mostly as a monotherapy
      (91% had one antidepressant), to the patients who were 65% female, aged 50.1 +/-
      8.9, most of them with 12 years of education (52.6%), married (69.3%) and
      employed (55.9%). The majority of patients had a history of two hospitalizations
      (Med 2; 25th-75th perc. 1-4) during nine years (Med 9; 25th-75th perc. 2-15)
      after the first episode of depression. Among them, 19% were found to be suicidal
      in a lifetime. The single most prescribed antidepressant was sertraline (20.4%),
      followed by fluoxetine (13.3%) and maprotiline (11.7%). Utilization of
      antidepressants was positively correlated with the rate of reimbursement (p <
      0.01). The most prescribed antidepressant group was selective serotonin reuptake
      inhibitors (SSRI) (47.8%), followed by tricyclic antidepresants (TCA) (25.3%) and
      new antidepressants - venlafaxine, tianeptine, mirtazapine, bupropion, trazodone
      (15.1%). Most of the drugs were prescribed in doses which are at the lower end of
      the recommended dose-range. Regarding severity of the actual depressive episode,
      TCA were prescribed for severe depression with psychotic features, while SSRI
      were choice for episodes with moderate symptom severity (p = 0.01). Psychiatrists
      with longer working age (20-30 years) hesitated to prescribe new antidepressants
      in comparison to younger colleagues (p = 0.01). CONCLUSION: Economic issues in
      Serbia as developing country influence the choice of antidepressants, as well as
      a psychiatrist's working age and severity of depression. However, SSRI are the
      drugs of the first choice, as it was shown in most of the developed countries
      nowadays.

PMID- 22624422
TI  - [Significance of pathohistological findings and the expression of Bcl-2 in
      diagnosis and treatment of oral planocellular carcinoma].
AB  - BACKGROUND/AIM: Numerous studies were aimed to detect and characterize various
      tumor markers in patients with oral planocellular carcinoma in order to reduce
      moratlity and mobidity rates of these patients, as well as to establish the
      correlation between the expression of specific tumor marker and prognostic
      outcome. The aim of this study was to determine patohistological characteristics
      of tumor and peritumor tissue in patients with oral planocellular carcinoma, with
      special regard to the expression of Bcl-2, as well as to point out the
      significance of clinicomorphological correlations for clinical use. METHODS:
      Sixty-two patients with oral planocellular carcinoma, stage II and III, were
      examined. The patients were surgically treated for this condition at the Clinic
      for Maxillofacial Surgery, Military Medical Academy, Belgrade. Surgical specimens
      were obtained from both tumor and peritumoral tissues. Patohistologic degree of
      tumor differentiation and the immunohistochemical expression of Bcl-2 were
      determinated for each specimens. RESULTS: Twenty-four (39%) patients had tumor
      dimension T1, while six (9%) and thirty-two (52%) patients had tumor dimension T2
      and T3, respectively. Patohistologic analysis of peritumor connective, fat,
      muscle and bone tissue samples confirmed the presence of tumor infiltration. The
      expression of Bcl-2 in peritumor tissue samples correlated significantly with
      tumor's histologic grade (rho = 0.468; p < 0.001), nuclear grade (rho = 0.430; p
      < 0.001) and nucleocytoplasmic ratio (rho = 0.410; p = 0.001). CONCLUSION: This
      results suggest that the expression of Bcl-2 in combination with patohistologic
      findings could have a prognostic value in patients with oral planocellular
      carcinoma.

PMID- 22624423
TI  - Microleakage, adaptation ability and clinical efficacy of two fluoride releasing
      fissure sealants.
AB  - BACKGROUND/AIM: Retention of fissure sealants and good adaptation to enamel are
      essential for their success. Fluoride releasing resin-based materials are widely
      accepted for pit and fissure sealing, but newly designed glass ionomers can serve
      as a good alternative. The aim of this study was to evaluate microleakage and
      sealing ability in vitro, and to clinically assess two fluoride releasing fissure
      sealants. METHODS: The sample for experimental study consisted of 20 freshly
      extracted intact human third molars, divided in two experimental groups according
      to the sealing material: fluoride releasing resin-based (Heliosel F) and glass
      ionomer (Fuji Triage) material. Digital images and scanning electron microscope
      were used to assess microleakage and adaptation ability. Sample for clinical
      study consisted of 60 children, aged 6-8 years, with high caries risk, divided in
      two groups according to the sealant material. Fissure sealant was applied to all
      erupted, caries-free first permanent molars. Sealants were evaluated after 3, 6
      and 12 months using modified Ryge criteria for retention, marginal adaptation,
      colour match, surface smoothness and caries. RESULTS: Microleakage was detected
      in more than half of the specimen, without significant differences between the
      two groups (p > 0.05). Both materials exhibited acceptable sealing ability.
      Complete retention at the end of the observation period was 81.8% for resin
      based, and 21.1% for glass-ionomer fissure sealant (p < 0.001). The presence of
      caries in sealed molars has been detected in one patient in both groups. During
      the 12-month observation period, Helioseal F demonstrated better retention,
      marginal adaptation and surface smoothness (p < 0.001). There were no differences
      between the two materials regarding caries and color match (p > 0.05).
      CONCLUSION: Both tested materials demonstrate satisfactory clinical and caries
      prophylactic characteristics that justify their use in contemporary preventive
      dentistry.

PMID- 22624424
TI  - [Differences in depression severity and frequency of relapses in opiate addicts
      treated with methadone or opiate blocker after detoxification].
AB  - BACKGROUND/AIM: Relapse of opiate dependence is a common occurrence after
      detoxification and introduction of opiate addicts in abstinence from opiates.
      Clinical evaluation showed that over 90% of opiate addicts exhibit depressive
      manifestations during detoxification, or develop post-detoxification depression.
      The aim of this study was to determine differences in the frequency of relapses,
      severity and course of depression during a of 6-month period, and previous
      patterns of use of opioids in the two groups of opiate addicts treated by two
      different therapeutic modalities. METHODS: The results of the two groups of
      opiate addicts were compared: the patients on substitution methadone treatment
      (M) and the patients treated with opiate blocker naltrexone (B). In all the
      patients, clinical and instrumental evaluations confirmed depressive syndrome.
      Opioid relapses were diagnosed by the panel test for rapid detection of
      metabolites of opiates in urine. Then they were brought in connection with scores
      of depression and addiction variables. The Hamilton Depression Scale (HAMD) and
      Zunge Depression Scale were the applied instruments for measuring the level of
      depression. All the subjects completed a questionnaire Pompidou (short version).
      Psychological measurements were carried out during a 6-month follow-up on three
      occasions. The presence of opiate metabolites in urine was controlled every two
      weeks. RESULTS: Both groups of patients (M and B) had high scores on HAMD during
      the study. The group on methadone had a strong depression in all three
      measurements. There was a drop in the level of depression in both experimental
      groups over time, which was accompanied by a decrease in the incidence of
      recurrence. In both tested groups the frequency of relapses was positively
      correlated with earlier addiction variables - intravenous application of opioids,
      the experience of overdose, the absence of immunization against hepatitis C and
      hepatitis C virus carriers. CONCLUSION: The opioid relapse behavior is associated
      with a marked depression in post-detoxification period. The tested group M had a
      more expressed depression which is consistent with the literature data. In both
      tested groups the frequency of relapses was positively correlated with individual
      addiction variables associated with latent suicidal behavior. Diagnosing and
      monitoring depression of opiate addicts as well as timely remediation of post
      detoxification depression symtoms, could help in prevention of opiate relapse.

PMID- 22624425
TI  - Knowledge of nursing students about central venous catheters.
AB  - BACKGROUND/AIM: Central venous catheters (CVC) are at the crucial importance,
      particulary in the intensive therapy units. In order to handle a CVC safely,
      nursing students need to acquire theoretical and practical knowledge during the
      course of their studies. The aim of the study was to establish theoretical
      knowledge of nursing students about the procedures of nurses in placing and
      removing a central venous catheter (CVC), dressing the catheter entry point, the
      reasons for measuring central venous pressure (CVP), possible complications and
      risk factors for developing infections related to CVC. METHODS: The questionnaire
      developed specifically for this cross-sectionl study was handed out to 87 full
      time students and 57 part-time students. RESULTS: The results show that all the
      surveyed nursing students know why chest radiography is carried out when
      inserting a catheter, have relatively good knowledge of CVC insertion points,
      procedures carried out in case of a suspected catheter sepsis and complications
      and risk factors for the development of infections related to CVC. However, the
      study show that the majority of students have insufficient knowledge of the
      procedures accompanying insertion of a catheter, signs that indicate correct
      functioning of CVC, frequency of flushing a catheter when it is not in use and
      the reasons for introducing an implanted CVC. CONCLUSION: Based on the results of
      the study it can be concluded that the second-year nursing students have
      insufficient knowledge of CVC. In order to correctly and safely handle a CVC,
      good theoretical knowledge and relevant practical experience are needed. The
      authors therefore believe that, in future, the classes should be organized in
      smaller groups with step-by-step demonstrations of individual procedures in
      handling a CVC, and the students encouraged to learn as actively as possible.

PMID- 22624426
TI  - Neonatal screening of hearing function by otoacustic emissions--a single center
      experience.
AB  - BACKGROUND/AIM: Nowadays development of techniques enables detection of hearing
      impairment in a very short time, immediately after birth by using otoacoustic
      emissions. They are low-pitched sounds produced in physiologically clear cochlea
      and can be recorded in cochlear outer meatus. By this method, complete data are
      found on a whole presynaptic auditory nervous system functioning that has mostly
      been affected by pathological changes making it a perfect screening test.
      Reliability and sensibility of this method is up to 98%. The aim of this study
      was to present the first results of systematic neonatal screening of hearing
      function by otoacoustic emissions in the Clinical Center Kragujevac (Kragujevac,
      Serbia). METHODS: This prospective study of neonatal hearing screening function,
      initiated systematically by the 2008 at the Clinical Center Kragujevac, included
      full-term newborns and premature born ones, within the first 24 h after birth,
      using a DPOAEs interacoustics otoread-screener. Retesting was done after a month.
      RESULTS: From January 1st, 2009 to December 1st, 2010, a total number of examined
      infants by this method was 1,994 out of which 1,778 were full-term and 216 were
      premature born. The test passing was higher in the group of full-term babies
      (92.5%) than in the preterm ones (55.1%). No bilateral answers were recorded in
      premature born children compared to the full-term ones, of whom a larger number
      was with missing lateral responses. The results of re-examination test in the
      group of full-term born and premature newborns were 83.7%, and 61%, respectively.
      CONCLUSION: Deliberately provoked transient otoacoustic emission is an efficient
      method in testing hearing function in newborns, since it is non-invasive, rapid
      and objective. Its correlation with audibly evoked potentials is very high, which
      confirms its reliability.

PMID- 22624427
TI  - Correlation of subtraction parathyroid scintigraphy with weight, pathohistologic
      finding and oxyphil cell content of parathyroid glands in parathyroid
      hyperplasia.
AB  - BACKGROUND/AIM: Parathyroid hyperplasia (PHP) is defined as an absolute increase
      in the mass of parenchymal cells of the parathyroid gland. PHP is classified as
      primary, secondary and tertiary. The enlargement of parathyroid glands (PG) is
      usually asymmetric, resulting in a "dominant" gland. In order to confirm the
      diagnosis, at least two glands should be examined histologically. Subtotal
      parathyroidectomy, i.e. removal of the three PG and leaving a small remnant of
      the forth, is the treatment of choice. High percent of PHP recurrence imposes the
      need for preoperative high sensitivity localizing procedures. Parathyroid
      scintigraphy localizes about 60% of hyperplastic glands. The aim of this study
      was to correlate findings of subtraction parathyroid scintigraphy (SPS) with
      weight, pathohistologic finding and oxyphil cell (OC) content of PG in patients
      with primary, secondary and tertiary parathyroid hyperplasia. METHODS: Twenty
      seven patients with primary/secondary PHP underwent SPS before surgery.
      Scintigraphic results were graded from 1-5, in relation to the degree of uptake.
      SPS graded 3, 4 and 5 were considered positive. The number and weight of operated
      PG were evaluated macroscopically. Pathohistologic and cellular types were
      defined on standard stained hematoxylin-eosin slides. OC content was defined as a
      percent of OC and graded from 1 to 3: grade 1 < 10%, grade 2 > or = 10% and grade
      3 > or = 20% of OC. RESULTS: SPS localized dominant gland in all patients with
      sensitivity 100%, and 51 from 73 hyperplastic PG, with sensitivity per gland of
      70%. PG weighed 0.1 g to 6.7 g (median 1 g). A significant positive correlation
      (p < 0.0001) was found between the SPS results and PG weight. A significant
      positive correlation was found between PG weight and OC content (p = 0.0002). An
      insignificant correlation was found between SPS and OC content. Thirty-eight PG
      had < 10% of OC, 32 PG had > or = 10% and 3 PG had > or = 20% of OC. Four
      patients had diffuse PHP and 23 patients nodular PHP. There was no statistically
      significant difference in SPS results compared to hyperplasia type, and between
      OC content and hyperplasia type. A significant positive correlation (p = 0.05)
      was found between PG weight and hyperplasia type. CONCLUSION: A high positive
      correlation was found between SPS results and PG weight, PG weight and OC content
      and PG weight and hyperplasia type. Between SPS results and OC content, and
      between SPS results and hyperplasia type, an insignificant correlation was found.
      Our results showed that SPS is a reliable and very sensitive diagnostic tool in
      detecting abnormal PG in parathyroid hyperplasia, reaching 100% sensitivity in
      detecting a "dominant gland" and sensitivity per localized gland of 70%. Causes
      that affect increased uptake of liposolubile Tc99m radiopharmaceuticals (RF) in
      the hyperfunctional PG tissue and conditions which prevent RF admission into the
      PG cells still remain to be accurately and precisely determined.

PMID- 22624428
TI  - Advantages and limitations of clopidogrel response testing methods.

PMID- 22624429
TI  - [Autoimmune polyglandular syndrome, type 2 associated with myasthenia gravis].
AB  - INTRODUCTION: Autoimmune polyglandular syndrome type 2 is defined as adrenal
      insufficiency associated with autoimmune primary hypothyroidism and/or with
      autoimmune type 1 diabetes mellitus, but very rare vith myasthenia gravis. CASE
      REPORT: We presented a case of an autoimmune polyglandular syndrome, type 2
      associated with myasthenia gravis. A 49-year-old female with symptoms of muscle
      weakness and low serum levels of cortisol and aldosterone was already diagnosed
      with primary adrenal insufficiency. Primary hypothyroidism was identified with
      low values of free thyroxine 4 (FT4) and raised values of thyroidstumulating
      hormone (TSH). The immune system as a cause of hypothyroidism was confirmed by
      the presence of thyroid antibodies to peroxidase and TSH receptors. Myasthenia
      gravis was diagnosed on the basis of a typical clinical feature, positive
      diagnostic tests and an increased titre of antibodies against the acetylcholine
      receptors. It was not possible to confirm the immune nature of adrenal
      insufficiency by the presence of antibodies to 21-hydroxylase. The normal
      morphological finding of the adrenal glands was an indirect confirmation of the
      condition as well as the absence of other diseases that might have led to adrenal
      insufficiency and low levels of both serum cortisol and aldosterone. Hormone
      replacement therapy, anticholinergic therapy and corticosteroid therapy for
      myasthenia gravis improved the patient's general state of health and muscle
      weakness. CONCLUSION: This case report indicates a need to examine each patient
      with an autoimmune disease carefully as this condition may be associated with
      another autoimmune diseases.

PMID- 22624430
TI  - External ear canal cholesteatoma after ventilation tube insertion and
      mastoidectomy.
AB  - INTRODUCTION: Etiopathogenetically, there are two types of chollesteatomas:
      congenital, and acquired. Numerous theories in the literature try to explain the
      nature of the disease, however, the question about cholesteatomas remain still
      unanswered. The aim of the study was to present a case of external ear canal
      cholesteatoma (EEC) developed following microsurgery (ventilation tube insertion
      and mastoidectomy), as well as to point ant possible mechanisms if its
      development. CASE REPORT: A 16-year-old boy presented a 4-month sense of fullness
      in the ear and otalgia on the left side. A year before, mastoidectomy and
      posterior atticotomy were performed with ventilation tube placement due to acute
      purulent mastoiditis. Diagnosis was based on otoscopy examination, audiology and
      computed tomography (CT) findings. CT showed an obliterative soft-tissue mass
      completely filled the external ear canal with associated erosion of subjacent the
      bone. There were squamous epithelial links between the canal cholesteatoma and
      lateral tympanic membrane surface. They originated from the margins of tympanic
      membrane incision made for a ventilation tube (VT) insertion. The position of VT
      was good as well as the aeration of the middle ear cavity. The tympanic membrane
      was intact and of normal appearance without middle ear extension or mastoid
      involvement of cholesteatoma. Cholesteatoma and ventilation tube were both
      removed. The patient recovered without complications and shortly audiology
      revealed hearing improving. Follow-up 2 years later, however, showed no signs of
      the disease. CONCLUSION: There could be more than one potential delicate
      mechanism of developing EEC in the ear with VT insertion and mastoidectomy. It is
      necessary to perform routine otologic surveillance in all patients with tubes.
      Affected ear CT scan is very helpful in showing the extent of cholesteatoma and
      bony defects, which could not be assessed by otoscopic examination alone.

PMID- 22624431
TI  - Atypical presentation of cystic fibrosis--obese adolescent with hypertension and
      pseudo-Bartter's syndrome.
AB  - INTRODUCTION: Infants with cystic fibrosis may fail to thrive despite recommended
      caloric intake because of electrolyte disurbances caused by salt depletion
      resulting in hypochloremic metabolic alkalosis or pseudo-Bartter's syndrome. In
      most patients reported symptoms began in infancy, but it may be an initial
      presentation of disease in a previously healthy adolescent. CASE REPORT: A 15
      year-old boy was admitted for evaluation of recurrent episodes of malaise
      associated with dehydration and acute renal insufficiency. Laboratory analysis
      showed hypochloremic metabolic alkalosis with hyponatremia and hypokalemia. On
      admission the boy was obese, with body weight of 95.5 kg (> P97), height 174 cm
      (> P75), and body mass index of 31.2 kg/m2 (> P95). Physical examination was
      inconclusive. Blood pressure holter monitoring proved significant systolic
      hypertension. Routine urinalysis, protein and electrolyte levels in urine were
      normal. Plasma renin and aldosteron were normal. Sweat chloride concentration was
      63 mmol/L. Genetic testing confirmed the diagnosis of cystic fibrosis.
      CONCLUSION: To our knowledge, this is the first reported case of atypical
      presentation of cystic fibrosis in an adolescent presented with pseudo-Bartter's
      syndrome and signs of obesity and hypertension. We suggest that every patient
      with hypochloremic metabolic alkalosis should be evaluated for cystic fibrosis.

PMID- 22624432
TI  - Unilateral presentation of pseudo-Kaposi's acroangiodermatitis--a diagnostic and
      therapeutic challenge.
AB  - INTRODUCTION: Acroangiodermatitis is a rare skin disease characterised by
      hyperplasia of pre-existing vasculature due to venous hypertension from severe
      chronic venous stasis. Clinical appearance of this condition is often similar to
      Kaposi sarcoma and is creating serious differential diagnostic difficulties. CASE
      REPORT: A patient with acroangiodermatitis was presented and the differential
      diagnosis discussed. Examination of the patella of the affected area showed
      grayish-blue to brown infiltrates and reduced elasticity, located in the supra-
      and infrapatellar regions. Clinically, Kaposi's sarcoma was suspected.
      Histopathologically there were acanthosis and compact hyperkeratosis. The
      underlying papillary dermis showed fibrosis and edema. A subepidermal lobular
      vascular proliferation with hemosiderin deposition was also noted. This consisted
      of multiple newly formed capillaries, featuring small blood vessels with dilated,
      rounded lumina. Serologies for HIV and Borrelia burgdorferi were negative, as was
      a HHV-8 PCR in lesional tissue. Doppler analysis of the vessels of the
      extremities showed chronic venous insufficiency, insufficiency of v. perforantes,
      insufficiency of the Cockett II-III. No deep thromboses in the area of the shank
      and thigh were found. Initially, treatment consisted of clindamycin 600 mg 3
      times per day, intravenously, during a 2-week period. After that the treatment
      was continued with prednisolone, 30 mg daily in combination with furosemide 40
      mg/day, as well as lymph drainage and adequate compression therapy. The
      consequent clinical improvement allowed the patient to be discharged from the
      clinic. CONCLUSION: The most important differential diagnostic marker in
      distinguishing between acroangiodermatitis and Kaposi sarcoma seems to be the
      confirmation of the presence of genetic material of HHV-8 in the affected skin
      areas in patients with Kaposi sarcoma.

PMID- 22624433
TI  - Food allergy epidemic: can we reverse the trend?

PMID- 22624434
TI  - Human milk fatty acids profile changes during prolonged lactation: a cross
      sectional study.
AB  - BACKGROUND: Human milk produced during prolonged lactation (> 1 year) is
      extraordinarily rich in fat and has a higher energy content than human milk
      produced during short lactation. OBJECTIVES: To estimate the fatty acid (FA)
      profile of human milk and to test the hypothesis that the proportion of C12 and
      C14 (two dietary saturated FA known to most promote hypercholesterolemia) in
      human milk during prolonged lactation is similar to that in short lactation.
      METHODS: We conducted a cross-sectional study of 30 mothers of term infants
      lactating for more than 1 year as compared with 25 mothers of full-term infants
      who lactated for 2-6 months. Milk was collected by manual expression in mid
      breastfeeding. RESULTS: The two groups did not differ in maternal height, weight,
      body mass index, diet, infant birth weight and gestational age, but mothers in
      the prolonged lactation group were significantly older. There was a significant
      correlation between lactation duration and C12 or C14. The percentage of all FA
      combined (except for C12 and C14) decreased significantly overtime. In contrast,
      C12:0 and C14:0 combined increased significantly during lactation (R2 = 10.0%, P
      < 0.03). CONCLUSIONS: Women who lactated for more than 1 year had higher C12 and
      C14 FA percentages in their milk than women who lactated for 2-6 months.

PMID- 22624435
TI  - Isolated contact urticaria caused by immunoglobulin E-mediated fish allergy.
AB  - Fish is a common cause of food allergy. The reactions usually occur after its
      ingestion. In most immunoglobulin E-mediated reactions, the allergens are
      gastroresistant and heat-stable proteins of low molecularweight (parvalbumin). On
      the other hand, isolated contact urticaria following the handling of raw fish but
      without symptoms after its ingestion was found among cooks and professional fish
      handlers. In these cases, the fish allergens are gastrosensitive and
      thermolabile, as demonstrated by the decrease in the diameter of the wheal in the
      skin-prick test using cooked fish. To the best of our knowledge isolated fish
      contact urticaria in children has not been previously reported. We analyze the
      features of three pediatric cases of contact urticaria from cod (one of them was
      sensitized to parvalbumin), with tolerance after ingestion of this fish on oral
      food challenge.

PMID- 22624436
TI  - Effect of instruction on the ability to use a self-administered epinephrine
      injector.
AB  - BACKGROUND: Patients with allergy as well as their parents frequently fail to use
      the self-administered epinephrine injection (EpiPen) properly in cases of
      allergic emergencies. OBJECTIVES: To determine the benefit of an instruction
      session with follow-up instruction. METHODS: We evaluated 141 patients aged 1.9
      23.4 years (median 5.8 years, 83% with food allergy) or their parents (for those
      aged < 12 years) who were trained in the use of the EpiPen during the first
      diagnostic visit to the allergy clinic during 2006-2009. At the next follow-up
      visit, the patients or their parents were asked to list the indications for
      epinephrine administration and to demonstrate the five steps involved in using
      the EpiPen. Each step was scored on a scale of 0-2. RESULTS: Fourteen
      participants (9.9%) had used self-injectable epinephrine in the past. Only 65
      (46%) brought the device with them to the follow-up visit. The mean total score
      for the whole sample was 4.03 +/- 3. Fifty-three participants (38%) failed to
      remove the cap before trying to apply the device. Only 8 (5.6%) had a maximum
      score. The patients and their parents were reinstructed in the use of the device:
      41 participants were reexamined at a subsequent follow-up visit after 1.02 +/-
      0.56 years; their mean score improved from 4.71 +/- 3.04 to 6.73 +/- 3.18 (P <
      0.001). CONCLUSIONS: Patients with severe allergic reactions, as well as their
      parents, are not sufficiently skilled in the use of the EpiPen after only one
      instruction session with a specialist. Repeated instruction may improve the
      results and we therefore recommend that the instructions be repeated at every
      follow-up visit.

PMID- 22624437
TI  - A new model for conservative food challenge in children with immunoglobulin E
      mediated cow's milk allergy.
AB  - BACKGROUND: The diagnostic gold standard for food allergy is an oral food
      challenge (OFC) with the suspected food. Usually, an OFC is stopped at the onset
      of mild objective symptoms for fear of severe reactions, but there is no
      consensus on this issue. OBJECTIVES: To investigate the effectiveness and side
      effects of a new model of oral milk challenge in order to increase the diagnostic
      accuracy of cow's milk protein allergy and reduce the number of useless
      elimination diets. This model is characterized by a conservative diagnostic
      protocol and "step-up cow's milk dosing." The secondary aim was to investigate
      possible factors influencing severe reactions. METHODS: Sixty-six children
      (median age 1 year, range 1-18) with suspected immunoglobulin E (IgE)-mediated
      cow's milk allergy performed a conservative OFC, i.e., the OFC was continued even
      in the presence of subjective, even repeated, or mild local or multiple organ
      objective symptoms. If the first objective reaction occurred when the quantity of
      milk was > 10 ml, the investigator would decide whether to continue the OFC or
      prescribe a gradual increase in milk feeding at home. RESULTS: Symptoms developed
      during the OFC in 42.4% of the children. Local, generalized and severe
      generalized reactions developed in 11 (16.7%), 11 (16.7%) and 6 (9.1%) children,
      respectively. Only 14/28 (50%) who developed objective symptoms during the OFC
      were considered to be affected by cow's milk allergy. In the remaining 14 both
      subjective and objective symptoms developed and the OFC was continued without
      further symptoms. Epinephrine was administered to 6 of the 28 children (21.4%)
      who developed objective symptoms. All but one had subjective symptoms following
      the early doses of milk, whereas all children who later tolerated milk had their
      first subjective or mild symptoms following doses > or = 10 ml. CONCLUSIONS: This
      new model of OFC criteria led to frequent severe allergic reactions; hence its
      use in daily practice seems inadvisable. However, our study provides evidence
      that a severe allergic reaction does not invariably occur if, the offending food
      continues to be administered after the onset of symptoms. If mild symptoms appear
      at doses > 10 ml, continued milk administration, on the same day or in subsequent
      days, seems to facilitate the development of tolerance and may reduce the number
      of useless elimination diets.

PMID- 22624438
TI  - Predictive values for food challenge-induced severe reactions: development of a
      simple food challenge score.
AB  - BACKGROUND: Skin-prick tests (SPT), food-specific immunoglobulin E level (sIgE)
      and clinical history have limited value individually in predicting the severity
      of outcome of the oral food challenge (OFC). OBJECTIVES: To develop a score that
      accounts for SPT, sIgE and clinical history to predict the risk of severe
      reaction to the OFC. METHODS: A 5 year retrospective chart review was performed
      on 983 children who underwent OFC to egg, milk and peanut. RESULTS: Using
      multilogistic regression, four major indicators were found to be independently
      associated with failed OFC: sIgE (odds ratio = 1.04, P < 0.0001), wheal size of
      the SPT (OR = 1.23, P < 0.0001), a history of any prior reaction to the food (OR
      = 1.13, P < 0.01), and a history of a prior non-cutaneous reaction (OR = 1.99, P
      < 0.01); and three were independently associated with anaphylaxis: wheal size (OR
      = 1.16, P < 0.001), a history of a prior non-cutaneous reaction (OR = 4.24, P <
      0.01), and age (OR = 1.07, P < 0.03). A Food Challenge Score (0-4) was developed
      which accounted for SPT wheal, sIgE, a history of a prior non-cutaneous reaction,
      and age. A score of 0-1 had a negative predictive value for multisystem reaction
      to the OFC: 95% for milk, 91% for egg and 93% for peanut. A score of 3-4 had a
      positive predictive value for anaphylaxis: 62% for milk, 92% for egg and 86% for
      peanut. CONCLUSIONS: Severe reaction to milk, egg and peanut OFC can be predicted
      using a simple score that takes into account clinical data that are commonly
      available prior to the challenges.

PMID- 22624440
TI  - Home-based oral immunotherapy protocol with pasteurized egg for children allergic
      to hen's egg.
AB  - BACKGROUND: In the last decade the use of different types of oral immunotherapy
      for food-allergic patients has increased with generally satisfactory outcomes.
      Cow's milk and hen's egg, a common element in the daily diet, have received the
      main interest. Most of these immunotherapy regimens are performed in the
      hospital, causing inconvenience for both children and their parents. OBJECTIVES:
      To assess the efficacy and safety of a home-based oral immunotherapy regimen with
      raw pasteurized egg. METHODS: The study group comprised children aged 6 years and
      older with allergy to hen's egg proteins, proven by positive skin prick-tests
      (SPT) and/orspecific immunoglobulin E (sIgE) and positive open oral food
      challenge (OOFC) with boiled or raw egg. Patients who met the inclusion criteria
      and signed the informed consent form underwent egg immunotherapy according to an
      established schedule. RESULTS: The treatment was given to 31 of the 36 recruited
      patients: 80.6% of the intention-to-treat population achieved complete tolerance
      to the maximum dose equivalent to one raw hen's egg, 3.2% achieved incomplete
      tolerance, and 16.2% did not achieve an acceptable tolerance dose. Most of the
      latter patients had a positive baseline OOFC with low doses of boiled egg. The
      average number of reactions per treated patient was 5.8, most of them grades 1
      and 2; there were no grade 4 reactions. CONCLUSIONS: This home-based oral
      immunotherapy protocol proved to effectively induce tolerance to hen's egg in
      most of the egg-allergic children and its safety profile was acceptable.

PMID- 22624439
TI  - Lessons from cases of mortality due to food allergy in Israel: cow's milk protein
      should be considered a potentially fatal allergen.
AB  - BACKGROUND: Most reports in the medical literature on food allergy mortality are
      related to peanut and tree nut. There is limited knowledge regarding these
      reactions and often only a partial medical history is described. OBJECTIVE: To
      record and characterize all known cases of mortality due to food allergy in
      Israel occurring during the period 2004-2011. METHODS: All cases of food allergy
      related mortality that were known to medical personnel or were published in the
      Israeli national communications media were investigated. We interviewed the
      parents and, when feasible, physicians who treated the final event. RESULTS: Four
      cases of food-related mortality were identified: three cases were due to cow's
      milk and one to hazelnut. All were exposed to a hidden/non-obvious allergen. All
      four had a history of asthma but were not on controller medications, and none had
      experienced previous non-life threatening accidental reactions. Three of the four
      patients had not been evaluated by an allergist, nor were they prescribed
      injectable epinephrine. The one patient who had been prescribed injectable
      epinephrine did not use it during her fatal anaphylactic attack. CONCLUSIONS:
      Fatal reactions to cow's milk and hazelnut but not to peanut are the only
      reported food mortality cases in Israel. Although these patients had previous
      reactions following accidental exposures, none had experienced a life-threatening
      reaction. Patients at risk are not adequately evaluated by allergists, nor are
      they prescribed and instructed on the proper use of injectable epinephrine. Cow's
      milk should be considered a potentially fatal allergen.

PMID- 22624441
TI  - Severe malnutrition resulting from use of rice milk in food elimination diets for
      atopic dermatitis.
AB  - BACKGROUND: Alternatives to cow's milk and soy milk are often necessary for
      children with food allergies. Although hydrolyzed and elemental formulas are
      appropriate replacements, other milk products such as rice and almond milk are
      insufficient protein sources for children under 2 years of age. A chart review on
      three patients treated for protein malnutrition in association with multiple
      diagnosed food allergies that resulted in refractory eczema revealed adverse
      outcomes that resulted from elimination diets. The use of rice milk resulted in
      hypoalbuminemia and poor weight gain in all cases, and multiple secondary
      infections in one patient. These cases illustrate the need for careful
      nutritional guidance in the management of food allergy, as well as the importance
      of cautious use and interpretation of testing for food allergies in the absence
      of a clear clinical history of reaction.

PMID- 22624442
TI  - Efficacy of oral immunotherapy protocol for specific oral tolerance induction in
      children with cow's milk allergy.
AB  - BACKGROUND: In the last two decades milkoralimmunotherapy has gained interest as
      an effective treatment option for milk-allergic patients. OBJECTIVES: To report
      on the efficacy of a milk oral immunotherapy. METHODS: Children with
      immunoglobulin E-mediated cow's milk allergy were included in the protocol. The
      treatment consisted of an induction phase in which milk doses were increased
      weekly in the hospital, while the tolerated dose was continued daily at home. The
      goal was to achieve a minimum milk intake of 200 ml a day. During the maintenance
      phase, patients ingested at least 200 ml of milk in a single dose every day.
      RESULTS: The protocol was applied to 105 milk-allergic children diagnosed by
      specific IgE to milk and controlled oral food challenge. The mean duration of the
      induction phase was 19 weeks. Of the 105 subjects, 86 (81.9%) successfully
      complied with the protocol and 19 (19.1%) failed. Causes of failure were
      moderate/severe reactions in 12 patients (12.44%) and personal reasons in 7
      (6.66%). A total of 182 adverse reactions occurred during the induction phase,
      most of them mild. Baseline specific IgE to milk and casein was significantly
      lower (P < 0.05) in the successfully treated group compared to the group in which
      the treatment failed. CONCLUSIONS: Milk oral immunotherapy is a safe and
      effective treatment for milk-allergic children, although adverse reactions may
      occur. Baseline milk and casein-specific IgE may be useful to predict a good
      response to milk oral immunotherapy.

PMID- 22624443
TI  - Predicting outcomes in food challenges: what's the score?

PMID- 22624444
TI  - Can feeding practices during infancy change the risk for celiac disease?

PMID- 22624445
TI  - Oral desensitization for immunoglobulin E-mediated milk and egg allergies.
AB  - Food allergy is an increasingly prevalent disease in western countries, but an
      effective form of therapy has not yet been found. A specific active treatment for
      immunoglobulin E (IgE)-mediated food allergy is currently under study in human
      clinical trials. Allergen-specific approaches include oral, sublingual and
      epicutaneous immunotherapy. Currently, reports on oral immunotherapy (OIT) have
      been more extensive than reports on other routes such as sublingual immunotherapy
      (SLIT) and epicutaneous patch. The aim of OIT using foods, especially milk and
      egg--the cause of most common allergies in infants and young children in Europe-
      is the achievement of desensitization or tolerance by patients suffering from
      food allergy. Treatment protocols have been initiated in highly supervised
      research settings with the goal of finding an active treatment against IgE
      mediated food allergy. The preliminary data on OIT are encouraging, and among the
      plethora of novel approaches the strategies most likely to advance into clinical
      practice include both OIT and SLIT. It is still unclear whether oral
      desensitization is only the first step toward permanent desensitization or
      whether it induces only a transient tolerance. Longer duration of desensitization
      may result in permanent tolerance. The occurrence of adverse events or reactions
      during OIT is quite frequent and has been reported in all published studies.
      Therefore, before this treatment can be used in clinical practice additional
      studies are needed. Currently, immunotherapy for cow's milk or egg allergies is a
      novel approach that expands the possibility of an active treatment to improve the
      quality of life of patients and their families.

PMID- 22624446
TI  - Early nutritional strategies for preventing allergic disease.
AB  - The rising number of children and adults with allergic disorders worldwide has
      prompted interest in strategies to prevent or reduce the risk of allergy. This
      article discusses the role of early nutritional strategies in the prenatal/
      postnatal periods that potentially may modify disease risk. Exclusive
      breastfeeding may help to prevent allergic disease by decreasing exposure to
      exogenous antigens, protecting against infections, promoting gastrointestinal
      mucosal maturation and the development of gut microbiota, and conferring
      immunomodulatory and anti-inflammatory benefits. However, the results of the
      studies are inconsistent, showing a protective effect, no effect, or even a
      predisposing effect. Still, breastfeeding should be promoted for its nutritional,
      immunological and psychological benefits. For infants with a documented
      hereditary risk of allergy (i.e., an affected parent and/or sibling) who cannot
      be breastfed exclusively, dietary products with confirmed reduced allergenicity
      are recommended. Previously, for complementary feeding, early exposure to solid
      foods during infancy was associated with the development of allergic diseases,
      particularly eczema. Currently, the guidelines downplaythe role of solid foods in
      the development of allergies, stating that there is no convincing scientific
      evidence that the avoidance or delayed introduction of potentially allergenic
      foods beyond 4-6 months reduces allergies in infants considered to be at
      increased risk for the development of allergic diseases or in those not
      considered to be at increased risk. Evidence from some trials with probiotics or
      prebiotic oligosaccharides suggests some benefits, but at present there is
      insufficient evidence to support their routine use. Neither can specific
      recommendations be made for the use of long-chain polyunsaturated fatty acids,
      antioxidants, folate, and vitamin D.

PMID- 22624447
TI  - Oral immunotherapy for the treatment of food allergy.
AB  - Food allergies have increased significantly over recent decades and are the most
      common cause of admissions for anaphylaxis in childhood, particularly in children
      under 5 years of age. Current management of food allergy is limited to strict
      food allergen avoidance together with education on the recognition and emergency
      management of allergic reactions, and in some cases provision of self-injectable
      adrenaline. Although this supportive management approach is generally effective,
      it is burdensome for patients and families, and in turn leads to reduced quality
      of life. Patients with food allergy would benefit greatly from a definitive
      treatment that could achieve long-term tolerance. Recent studies demonstrate that
      oral immunotherapy (OIT) can induce desensitization and modulate allergen
      specific immune responses. However, it remains uncertain whether long-term
      tolerance can be achieved with current OIT regimens. Increased allergen dose,
      duration of OIT and/or inclusion of an immune modifying adjuvant may enhance the
      tolerogenic potential of OLT. Allergic reactions during OIT are common, although
      severe reactions are infrequent. Oral immunotherapy holds promise as a novel
      approach to the definitive treatment of food allergy.

PMID- 22624448
TI  - Adult-onset food allergy.
AB  - The prevalence of food allergy is increasing in both the pediatric and adult
      populations. While symptom onset occurs mostly during childhood, there are a
      considerable number of patients whose symptoms first begin to appear after the
      age of 18 years. The majority of patients with adult-onset food allergy suffer
      from the pollen-plant allergy syndromes. Many of them manifest their allergy
      after exercise and consuming food to which they are allergic. Eosinophilic
      esophagitis, an eosinophilic inflammation of the esophagus affecting individuals
      of all ages, recently emerged as another allergic manifestation, with both
      immediate and late response to the ingested food. This review provides a
      condensed update of the current data in the literature on adult-onset allergy.

PMID- 22624450
TI  - Please, intubate me!

PMID- 22624449
TI  - The Dead Sea and SCHF patients with an ICD.

PMID- 22624451
TI  - Summary health statistics for the U.S. population: National Health Interview
      Survey, 2010.
AB  - OBJECTIVE: This report presents both age-adjusted and unadjusted health
      statistics from the 2010 National Health Interview Survey (NHIS) for the civilian
      noninstitutionalized population of the United States. Estimates are disaggregated
      by sex, age, race, Hispanic origin, education, family income, poverty status,
      health insurance coverage (where appropriate), place of residence, and region of
      residence. The topics covered are respondent-assessed health status, limitations
      in activities, special education or early intervention services, injury and
      poisoning episodes, health care access and utilization, and health insurance
      coverage. DATA SOURCE: NHIS is a household, multistage probability sample survey
      conducted annually by interviewers of the U.S. Census Bureau for the Centers for
      Disease Control and Prevention's National Center for Health Statistics. In 2010,
      household interviews were completed for 89,976 persons living in 34,329
      households, reflecting a household response rate of 79.5%. SELECTED HIGHLIGHTS:
      Nearly 7 in 10 persons were in excellent or very good health in 2010. About 38
      million persons (12%) were limited in their usual activities due to one or more
      chronic health conditions. About 5 million persons (2%) required the help of
      another person with activities of daily living, and about 9 million persons (4%)
      required the help of another person with instrumental activities of daily living.
      About 7% of children received special education or early intervention services.
      Among persons under age 65 years, about 48 million (19%) did not have any health
      insurance coverage. The most common reason for lacking health insurance was cost,
      followed by a change in employment.

PMID- 22624452
TI  - [The 33rd report on survey of the adverse reaction to radiopharmaceuticals (the
      36th Survey in 2010)].
AB  - This survey was performed in order to investigate the incidence of adverse
      reactions to radiopharmaceuticals in FY2010 in Japan. It was based on responses
      to questionnaires sent to nuclear medicine institutions. The reply was obtained
      from 961 institutions among 1,259 to which the questionnaire had been sent.
      Twenty-two cases of adverse reactions were reported. A total of 1,046,243
      radiopharmaceutical administrations was reported. The incidence of adverse
      reactions per 100,000 cases was 2.1. One case of defect products was reported,
      and the incidence of defect products per 100,000 cases was 0.1.

PMID- 22624453
TI  - [The biochemical markers of hypoxic perinatal affections of central nervous
      system in newborns].
AB  - The review analyses the clinical informativity of new biochemical markers of
      perinatal hypoxic affection of central nervous system in newborns--xanthine,
      hypoxanthine, adrenomedillin, protein S100B, activin A and neuron specific
      enolase.

PMID- 22624454
TI  - [The latex agglutination with video digital registration: the enhancement of
      diagnostic significance of conventional technique].
AB  - The rapid semiquantitative latex-tests, because of their analytic characteristics
      and convenient application, became widespread in the practice of laboratory
      diagnostics. Though, in spite of high sensitivity and specificity, their
      diagnostic effectiveness is lower that it could be mainly because of the
      impossibility to document the results of latex agglutinative re4actions and to
      manage the objective quality control. The application of systems of video digital
      registration permits to enhance the clinical significance of these analyses. By
      means of scanner systems (control and program complex "Expert Lab") the image of
      analytic objects is received with the results of latex agglutination reaction.
      The application of program techniques (the programs "Expert Lab - Agglutination"
      and "Expert Lab - Agglutination - Micros") in data processing permits to get the
      precise qualitative characteristics of active reactions, to ensure the automatic
      interpretation of results and gives an opportunity to proceed with the internal
      laboratory quality control. The saving of analytic object image in computer
      memory after termination of reaction favors the formation of data base, the
      implementation of retrospective evaluation of obtained results, additional
      consultations in dubious cases, including on-line. The application of complex
      "Expert Lab" permitted to develop the miniaturizes matrix systems permitting to
      decrease the withdrawal of latex reagents, to increase the productivity of
      analytical stage of operation preserving all analytical characteristics of
      method.

PMID- 22624455
TI  - [The alteration of threshold of clinical decision making in connection with the
      implementation of direct detection of cholesterol-low density lipoproteins in
      laboratory practice].
AB  - The retrospective study included 494 patients (the triglycerides level was less
      than 4.2 mole per liter) examined during January-March 2010 in four medical
      institutions of Volgograd and Voljsky. The comparative analysis was made of
      results of the Friedewald equation test and direct test of cholesterol-low
      density lipoproteins in the same samples. The correlation between the results of
      different tests of cholesterol-low density lipoproteins was low (R2=0.65). The
      labeling of patients as particular category according the results of testing of
      cholesterol-low density lipoproteins with different techniques matched only in
      55% of cases. At the same time, under direct testing of cholesterol-low density
      lipoproteins in 40% of cases the patients were labeled as low risk category.

PMID- 22624456
TI  - [The comparative analysis of electrophoretic fractionating of blood serum
      proteins in diagnostics of multiple plasma cell myeloma].
AB  - The choice of technology of electrophoretic fractionating of blood serum proteins
      is determined, besides the analytical characteristics, by its economic component.
      The electrophoresis technologies developed by the R&D production facility "Astra"
      (Russia) and the firm "PZ Cormay S.A." (Poland) are compared from a viewpoint of
      applicability in routine laboratory, practice and diagnostics of multiple plasma
      cell myeloma in particular. It is established that under the comparable economic,
      "consumer" and analytic characteristics of technologies in the diagnostic process
      the application of the technology in agarose gel ("PZ Cormay S.A.") is more
      preferable.

PMID- 22624457
TI  - [The characteristics of changes of indicators of hypophyseal-thyroid system and
      lipid metabolism in adolescents of different ethnic groups].
AB  - The girls and boys (the ethnic tofs) residing in the village of Alykdjer of
      Nijneudinsky district of Irkutsk oblast have been examined. The Irkutsk girls and
      boys (the Caucasians) made the comparison groups. In tof boys the activation of
      hypophyseal-thyroid system and activity increase of lipoprotein spectrum of blood
      serum was established. Furthermore, in the tof adolescents the level of
      liposoluble vitamin alpha-tocopherol is increased as compared with the Caucasians
      adolescents.

PMID- 22624458
TI  - [The laboratory diagnostics of fat embolism].
AB  - The examination was applied to 598 patients with polytrauma and patients after
      surgery on bones and joints on the subject of various diseases of locomotor
      apparatus. All patients were tested on fat embolism in blood serum and
      cerebrospinal fluid. The modificated Guard's technique was applied. The test data
      permitted to develop the method of express diagnostics of oil embolism. It is
      established that fat liquorglobulia is a pathognomonic symptom of cerebral form
      of fat embolism.

PMID- 22624459
TI  - [The characteristics of lipid spectrum of blood serum in native and alien
      population in Amur region].
AB  - The study was organized to establish the distinctive characteristics of lipid
      metabolism among the most numerous ethnic groups of native population in Amur
      region (Nanay, Ultch, Even) as compared with alien population. The technique of
      random sample was applied to examine 297 Even, 792 Ultch and 1274 Nanay (83.4%,
      83.5% and 77.5% of total residing population accordingly, aged from 30 to 70
      years and older). All examined persons were tested on whole cholesterol,
      triglycerides and cholesterol high-density lipoproteins in blood serum. The
      content of cholesterol high-density lipoproteins was calculated in mmol/l
      according the W. Friedwold equation. The examined group of alien population
      statistically did not differ. In all natives the indicators of lipid spectrum
      were more favorable on the average as compared with alien population. The
      differences were detected in native and alien population of Amur region
      concerning the lipid spectrum of blood. The levels of whole cholesterol,
      triglycerides and cholesterol high-density lipoproteins are reliably lower in
      males and females of Even and Nanay than in alien population residing next to
      them. This kind of difference concerning whole cholesterol and triglycerides is
      present among Ultch and Nanay as compared with alien males. The level of
      cholesterol high-density lipoproteins is lower in Ultchan females as compared
      with alien females. The level of cholesterol high-density lipoproteins is higher
      in all groups of native population than in alien populations.

PMID- 22624460
TI  - [The HPLC analysis of vanillil-almond, 5-hydroxiindolacetic, homovanillic and
      homogentisic acids in biologic fluids in clinical laboratory].
AB  - The simple and fast HPLC technique of analysis of vanillil-almond, 5
      hydroxiindolacetic, homovanillic and homogentisic acids in urine with solid-phase
      extraction using ultra cross-linked polystyrene (Purosep-200) is proposed. The
      separation on column Chromolith Performance RP-18e "Merck" 100x4.6 mm with
      monolithic phase-reversed silica gel in isocratic or gradient mode with
      ultraviolet detection under 285 nm. The isocratic mode is applied in case of
      ordinary analysis of vanillil-almond or homogentisic acids. The composition of
      eluent is isopropanol - water - TFA (1:99:0.025, v/v/v), flow speed is 1400
      mkl/min; pressure is 37 bar, full separation less than in 4 min. The gradient low
      pressure mode is applied to analyze vanillil-almond, hydroxiindolacetic and
      homovanillic acids. Under this approach the switching to second eluent occurred
      from second minute. The composition of eluent is isopropanol-water-TFA
      (6:94:0.025, v/v/v), flow speed is 1400 mkl/min, pressure is 43 bar, full
      separation is less than in 7 min. The output (extraction share) consisted 78
      113%. The simplicity reproducibility and sufficient sensitivity of technique in
      combination with the possibility of its application on standard chromatographic
      equipment (isocratic pump and ultraviolet detector) made it useful for routine
      clinical application.

PMID- 22624461
TI  - [The function of mitochondrion, carnitine, coenzyme-A, fat acids, glucose, the
      Randle cycle and insulin: a lecture].
AB  - In the function of feeding as biologic function of trophology, occurs the
      interchange of biologic reactions of exotrophy (postprandial hyperglycemia and
      hyperlipidemia) and periods of food absence (biologic reaction of endotrophy).
      The action of insulin is realized in the biologic reaction of exotrophy only. The
      phylogenetic late insulin manages the function of phylogenetic early
      mitochondrion in the biologic reaction of exotrophy. In the biologic reaction of
      exotrophy, the cells activatedly absorb glucose under effect of insulin through
      glucose carriers-4 and actively absorb fat acids in the form of nonpolar
      triglycerides in olein lipoproteins of very low density by force of receptor
      endocytosis. These mechanisms formed on late stages of phylogenesis in the
      becoming of biologic function of locomotion--the function of movement. In the
      biologic reaction of endotrophy the cells absorb passively glucose under effect
      of glycaemia in intercellular medium through glucose carriers and passively (on
      gradient of concentration) absorb the fat acids in polar form under passive
      diffusion through plasmatic membrane. These reactions are worked out on the early
      stages of phylogenesis in the becoming of biologic function of homeostasis. The
      syndrome of resistance to insulin is formed only in biologic reaction of
      exotrophy but the disorders can persist and during realization of biologic
      reaction of endotrophy. In the biologic reaction of exotrophy insulin "decides":
      a) glucose can be deposited only in a limited way and can be consumed (oxidized
      in mitochondrion) in the first instance: b) fat acids can be stored and kept to
      be used in biologic function of locomotion. In the biologic reaction of exotrophy
      insulin "endeavors" as fast and full as possible use glucose and preserve in vivo
      as much as possible of fat acids as a substratum for further realization of
      biologic function of locomotion. Insulin minimizes in cytosol the content of a)
      ketone bodies - metabolites of C4 butyric fat acid and b) short chained C6-C10
      fat acids and C16 palmitic acid for which in mitochondrion exists specific
      carrier - carnitin-palmitoilacyltransferase and "forces" mitochondrion to oxidize
      glucose. The main biologic role of insulin is to provide the biologic function of
      locomotion with substratum of energy

PMID- 22624462
TI  - [The dynamics of indicators of hemostasis in case of physiologically progressing
      pregnancy].
AB  - The conditions of vascular thrombocyte, coagulator and fibrinolytic components of
      hemostasis were evaluated in trimestral dynamics in 65 healthy pregnant women
      without thrombotic risk factors and with physiologically progressing pregnancy
      resulted in timely delivery of term fetus. In the process of gestation, the
      increase of spontaneous and induced aggregative activity of thrombocytes, the
      increase of levels of fibrinogen, soluble fibrin monomeric complexes. D-dimer and
      fibrinolysis delay were established.

PMID- 22624463
TI  - [The impact of gen polymorphism of subunits of receptors of thrombocytes GP
      IIb/IIIa on variation of indicators of thrombocyte hemostasis in obstetrics
      practice].
AB  - The article presents the results of study of the impact of gen polymorphism of
      subunits of receptors of thrombocytes GP Ilb/IIIa on variation of quantitative,
      functional and morphometric parameters of thrombocytes in 408 puerperae. The
      heterozygous variant of mutation was established in women with physiologically
      progress of pregnancy and delivery and in women with clinical manifestations of
      thrombophilia. The homozygous variant was established only in women with
      thrombophilia. The relationship is established between the presence of hetero-
      and homozygous mutations of gen of subunits of receptors of thrombocytes GP
      IIb/IIIa and inclination to hypercoagulation. This relationship manifests itself
      in increasing of degree of thrombocytes aggregation with all inductors and as
      well as in increasing of functional activity and appearance of young active
      cells, according morphometric analysis data. The application of computer
      morphometry of thrombocytes in the study made it possible to ascertain the
      activization of thrombocyte component of hemostasis in healthy women and
      availability of heterozygous mutation of gen of subunits of receptors of
      thrombocytes GP IIb/IIIa (PlA1/PlA2).

PMID- 22624464
TI  - [The molecular markers of systemic inflammation response and hemocoagulation in
      case of endoprosthesis replacement of articulation of hip].
AB  - The groups with "compensated" and "decompensated" conditions of organism are
      marked out according the level of sICAM-1 and neopterin. The surgery of
      endoprosthesis replacement results in the development of systemic inflammation
      response syndrome (manifestation of hemostatic and adhesional dysfunctions of
      endothelium depends on pre-surgery condition of vessel wall). To forecast the
      risk of development of post-surgery thromboembolic and inflammatory complications
      it is appropriate to study the content of sICAM-1 and neopterin in pre-surgery
      period.

PMID- 22624465
TI  - [The test system to identify mucin MUC1 in human blood serum using the technique
      of immune-enzyme analysis based on monoclonal antibody ICO25].
AB  - On the basis of genuine mouse monoclonal antibody ICO25 the test system IEA ICO25
      was developed and standardized to quantitative detect tumor-associated antigen,
      mucin1 in human blood serum in format of inhibitory immune-enzyme analysis. The
      analytic characteristics of test-system correspond to the standards applied to
      immune-enzyme diagnostic kits. The results of identification of MUC1 in blood
      serum of healthy donors and female patients with breast pathology using IEA ICO25
      fully correlate with the data concerning the detection of antigen CA15-3 using
      certified commercial kits. The test system IEA ICO25 can be used to detect MUC1
      in human blood serum for research purpose.

PMID- 22624466
TI  - [Estimation of the minimum infective doses of HIV in the prevalence of its
      infection].
AB  - Estimation of the minimum human infective doses of HIV is essential to the
      prediction of its infection prevalence, including in bioterrorism. Information on
      the epidemiology and pathogenesis of HIV infection and on the biological
      properties of the pathogen may serve as reference data for the theoretical
      determination of a rough infective dose of HIV. The most common route of virus
      infection is parenteral transmission. The likelihood of HIV transmission through
      blood depends on the frequency of transfusions, the stage of HIV infection in a
      donor and the amount of blood given to a recipient. The author has analyzed the
      data available in the literature on the epidemiology and pathogenesis of the
      infection, on the properties of the pathogen, and on the risks of HIV infection
      in different groups and summarized information on the infection among injecting
      drug users, which could roughly estimate the level of sensitivity in man as a
      biological species to this virus.

PMID- 22624467
TI  - [Universal influenza vaccines: developments, prospects for use].
AB  - The review analyzes the developments of genetic engineering influenza vaccines
      based on the conservative epitopes of viral surface proteins, such as
      hemagglutinin, neuraminidase, ectodomain of matrix protein M2. It estimates the
      capacity of the vaccines to induce an immune response to a wide variety of
      influenza viruses, considers ways to increase the immunogenicity and protective
      properties of the vaccines, based on the conservative epitopes of viral surface
      proteins, and prospects for their use to prevent influenza.

PMID- 22624468
TI  - [Correlation between the receptor specificity of pandemic influenza A (H1N1)pdm09
      virus strains isolated in 2009-2011 and the structure of the receptor-binding
      site and the probability of fatal primary viral pneumonia].
AB  - The receptor specificity (RS) of pandemic influenza A(H1N1) pdm09 virus strains
      deposited into the State Collection of Viruses of the Russian Federation, D. I.
      Ivanovsky Research Institute of Virology, Ministry of Health and Social
      Development of Russia, in the 2009-2010 and 2010-2011 epidemic seasons to a panel
      of 9 sialoglycopolymers (SGP). The strains were divided into 3 groups according
      to the W(3/6) index proposed by the authors, which was equal to the amount of
      reactivities to unbranched alpha2-3-SGP to that of reactivities to unbranched
      alphal-6-SGP: W(3/6) < or = 1.0; 1.0 < W(3/6) < or = 1.5. The W(3/6) < or = 1.5
      group showed a predominance of a2-3-RS, attended by the high incidence of fatal
      primary viral pneumonias (FPVP) (60.0%) and amino acid replacements in the HA1
      receptor-binding site (RBS) (80.0%): D222{G, N} and Q223R. The 1.0 < W(3/6) < or
      = 1.5 group was characterized by mixed alpha2-3/alpha2-6-RS with the incidence of
      FPVP (29.7%) and amino acid replacements in the HA1 RBS (40.5%) (D222{G, N, V}
      and Q223), respectively. In the W(3/6) < or = 1.0 group, alpha2-6-RS was
      prevalent, FPVPs were absent and amino acid replacements in HA1 RBS (D222{G, E})
      were seen only in 6.0% of cases. The number of strains with increased specificity
      to alpha2-3-sialosides increased in the 2010-2011 epidemic season as compared to
      the previous season. With their further spread among the population, there may be
      a rise in cases of severe primary viral pneumonias with possible fatal outcomes,
      which can be, however, accompanied by a decrease in the capacity of mutants to
      air-dropwise transmission.

PMID- 22624469
TI  - [The specific features of the cocirculation of influenza viruses in the 2010-2011
      postpandemic period according to the results of activities of the D. I. Ivanovsky
      Research Institute of Virology, Ministry of Health and Social Development of
      Russia].
AB  - The paper gives the results of monitoring the circulation of influenza viruses in
      the 2010-2011 season, that covers the second year of circulation of pandemic
      A(H1N1)v virus strains, and their interaction with seasonal A (H3N2) and B
      strains. Unlike the previous season, the beginning of an increase in morbidity
      was recorded in January 2011; its peak in the most of contiguous areas was noted
      at 5-7 weeks of 2011, with its further decline to threshold levels at week 11 of
      2011. Preschool and school children were most involved in the epidemic process.
      Three influenza virus strains (A(H1N1)v, A(H3N2), and B) were found to circulate.
      Differences were found in the level of participation of the isolated strains in
      individual areas of the Russian Federation. Detailed typing of the isolated
      strains determined the compliance of the vast majority of them with vaccine
      viruses. The pandemic influenza A(H1N1)v virus strains retained their
      susceptibility to oseltamivir and were resistant to rimantadine. The
      participation of non-influenza acute respiratory viral infection pathogens was
      estimated as follows: 11.9% for parainfluenza viruses, 5.9% for adenoviruses, and
      3.5% for PC viruses, and 0.7% for pneumonia Mycoplasma, which was comparable with
      the previous epidemic seasons.

PMID- 22624470
TI  - [Increasing the immunogenicity of inactivated chitosan adjuvanted vaccine from
      A/California/7/09 (H1N1) strain and analyzing the antigenic specificity of this
      influenza virus strain].
AB  - Addition of chitosan as an adjuvant to subunit vaccine from the swine origin
      influenza virus A/California/7/09 (H1N1) increases vaccine immunogenicity by 8-16
      times and significantly enhances its protective potency. Single immunization with
      chitosan adjuvanted vaccine induced similar antibody titers as two immunizations
      with unadjuvanted vaccine. Chitosan stabilized the immunogenicity of subunit
      vaccine when stored at 4 degrees C. The antigenic specificity of the
      A/California/7/09 (H1N1) virus strain did not resemble substantially that of the
      human influenza strains A/Brisbane/59/07 (H1N1) and A/Solomon Isles/3/06 (H1N1),
      which are among the 2008/2009 and 2007/2008 seasonal influenza vaccines,
      respectively, as well as that of the human influenza H1N1 virus strains that
      circulated about 30 years ago.

PMID- 22624471
TI  - [In vitro investigation of the antiviral activity of Ingavirin against human
      metapneumovirus].
AB  - The antiviral activity of Ingavirin against human metapneumovirus (HMPV)
      infection was investigated in vitro. The investigation used the human cell line
      ChangConjunctiva, permissive for HMPV, clone 1-5C4, and the HMPV strain isolated
      at the D. I. Ivanovsky Research Institute of Virology. The experimental studies
      suggest that when added at a concentration of 50 to 500 microg/ml to a nutrient
      medium 24 hours after HMPV infection, Ingavirin suppressed effectively virus
      replication by 2.2-3.3 logs, respectively. When used at a concentration of 500
      microg/ml 24 hours before cell infection, Ingavirin protected cells from HMPV
      infection.

PMID- 22624472
TI  - [Stimulation of homo- and heterologic T-cell immunological memory in volunteers
      inoculated with live influenza A (H5N2) reassortant vaccine].
AB  - The study deals with the ability of live attenuated reassortant influenza vaccine
      (LAIV) A (H5N2) to stimulate a CD4+ and CD8+ immunological memory T cell-mediated
      immune response in volunteers. These data were compared with the quantitative
      characteristics of a humoral immune response. A two-dose regimen of intranasal
      vaccination of avian influenza naive people with A (H5N2) LAIV induced the
      production of circulating CD4+ and CD8+ memory cells specific to both A (H5N2)
      and seasonal A (H1N1) influenza strains. Some of the volunteers were not
      absolutely A (H5N2) influenza virus naive since they had been found to have this
      virus-specific cross-reactive immunological memory T-cells in the prevaccination
      period. The content (%) of these cells varied significantly within the group. The
      quantitative values of postvaccination CD4+ and CD8+ memory cell accumulation
      were inversely related to their prevaccination level.

PMID- 22624473
TI  - [Evaluation of the efficiency of differential diagnosis of influenza by multiplex
      real-time polymerase chain reaction].
AB  - The paper gives the results of a comparative analysis of the detection of
      influenza viruses in clinical samples, by using multiplex real-time polymerase
      chain reaction (RT-PCR) and by virus isolation in MDCK cell cultures. The
      investigation employed 267 nasopharyngeal swab specimens obtained from patients
      with influenza symptoms during two epidemic seasons (2008-2009 and 2009-2010).
      Influenza viruses were found in 104 samples (48 with influenza A virus (IAV) and
      56 with influenza B virus (IBV)) by multiplex RT-RCR and in 84 samples (35 with
      IAV and 49 with IBV) by a cultural technique. The results of detection of
      influenza viruses by the two methods showed 89.4% agreement. The diagnostic
      sensitivity of multiplex RT-PCR testing a panel of the clinical samples in
      question was estimated to be 94.3% for IAV and 95.9% for IBV. The diagnostic
      sensitivity of multiplex RT-PCR in virus detection was demonstrated to be not
      only highly competitive with virus isolation, but also superior to the latter.

PMID- 22624474
TI  - [Design of a polymer drug for serological diagnosis of hepatitis C].
AB  - A new immunobiological polymer drug has been designed for the serological
      identification of hepatitis C. The drug is able to reveal specific antibodies in
      the sera of patients with hepatitis C, meets the current requirements of
      diagnostic test systems, and shows a high sensitivity and specificity. It is
      based on polyacroleinic microspheres; the concentrated cell culture biomass of
      hepatitis C virus (HCV), which contains an adequate set of viral antigens, is
      used as sensitin. A new diagnosticum is proposed to be used during primary
      (screening) laboratory studies based on the serological detection of total
      antibodies to HCV antigens in the volume agglomeration test. The latter is both
      one of the alternative methods during serological studies and an additional
      procedure when a set of diagnostic techniques is used.

PMID- 22624475
TI  - [The problems of studying the effects of far long-duration space mission factors
      on the higher nervous activity in model experiments with animals].
AB  - The article presents the analysis of difficulty with studying the CNS functional
      changes caused by ionizing radiations solely and in combination with the other
      spaceflight factors, and discusses optional methods of modeling the basic
      elements of operator's work in experiments with animals, primates specifically,
      as well as of data extrapolation on humans.

PMID- 22624476
TI  - [Influence of simulated hypomagnetic environment in a far space flight on the
      rhythmic structure of rat's behavior].
AB  - Behavior of a group of rats was observed visually and tape recorded continuously
      from day 19 till the end of 25-d hypomagnetic experiments. Results were
      statistically processed with the help of Statistica 6.0, time series spectral
      analysis, and cosinor analysis. The 25-d HM exposure was shown to suppress food
      motivated behavior in the mornings on the background of step-up in serotoninergic
      processes in the brain, and exaggerate the intraspecific violent conduct at
      night. The hypogeomagnetic environment impacted diurnal system adaptability to
      the seasonal light period drifting and produced exo- and endogenous
      desynchronosis.

PMID- 22624478
TI  - [Rates of aberrant lymphocytes elimination in various bio-objects].
AB  - Rate of damaged cells elimination in mammals after prolonged irradiation modifies
      frequency of chromosomal aberrations (CAF) significantly. Hence, CAF is unlikely
      to be identical in a bio-object exposed to equal doses with varying dose rate for
      the reason of different periods of ionizing irradiation. This should be taken
      into account by designers of bio-dosimeters. Main time characteristics of
      chromosomal aberrations in mammals can be calculated from the experimentally
      evidenced CAF growth in the course of irradiation and decline afterwards. This
      assumption was tested using the data about disaster fighters at the Chernobyl
      nuclear power station and of experiments with chronic and fractionated exposure
      of rhesus macaques to 2.5 Gy (Cs137). The experimental doses ranged from 25 cGy
      to 250 cGy; dose rate made up 1.4 and 20 cGy/hr. Therapeutic doses were within
      the interval of 1.2 to 9.8 Gy. Rate of aberrant cells elimination was determined
      for two objects, i.e. humans and rhesus macaques. The follow-up period was
      approx. 6 years (61 to 2174 days). Elimination rate in the experiment was
      estimated using a proposed mathematical description of CAF dynamics in peripheral
      blood lymphocytes of monkeys. Elimination rates of aberrant peripheral
      lymphocytes in two bio-species were compared. The parameter is equal to (2 +/-
      0.5).10(-3) d(-1) and (16 +/- 3) x 10(-3) d(-1) for the human and rhesus macaque,
      respectively.

PMID- 22624477
TI  - [Evaluation of the risk of delayed adverse effects of chronic combined exposure
      to radiation and chemical factors with the purpose to ensure safety in orbital
      and exploration space missions].
AB  - The work had the aim to anatomize the existing issues with providing safety in
      extended orbital and exploration missions for ensuing estimation of actual values
      of the total radiation risk for the crew, and risks of other delayed effects of
      simultaneous exposure to ionizing radiation and chemical pollutants in cabin air,
      and a number of other stressful factors inevitable in space flight. The flow of
      chronic experiments for separate and combined studies with reproduction of air
      makeup and radiation doses in actual orbital and predicted exploration missions
      is outlined. To set safety limits, new approaches should be applied to the
      description of gradual norm degradation to pathologies in addition to several
      generalized quantitative indices of adaptation and straining of the regulatory
      systems, as well as of effectiveness of the compensatory body reserve against
      separate and combined exposure.

PMID- 22624479
TI  - [Gamma-radiation action on cells of algae Euglena gracilis].
AB  - Considering the potentials of algae Euglena to constitute a part of biological
      systems of human life support, effects of low radiation doses on algal cells and
      radiosensitivity dependence on their genotype were studied. In experiments with
      gamma-irradiation (60Co) of Euglena gracilis, the highest radioresistance was
      demonstrated by strain Z. OFL; the chloroplasts lacking Z-derived strain showed
      hypersensitivity to radiation. E. bacillaris and derived chlorophyll-lacking
      strains W3 and W10 had intermediate radiosensitivity. Irradiation with the doses
      of up to 10 Gy produced a hormetic effect in the stock strains. Cells death was
      observed only after irradiation by doses above 100 Gy. The stimulating effect was
      exerted both on radioresistance and growth rate. Dyes made possible rapid
      evaluation of the proportion of living and dead cells. Comparison of two survival
      tests showed that the classic medium inoculation overestimates cell deaths as it
      disregards the living non-proliferating cells.

PMID- 22624480
TI  - [Desmin content and cell breathing in rats' m. soleus fibers after 3- and 7-day
      recovery from 14-day suspension].
AB  - Cell breathing and relative desmin content were investigated in m. soleus fibers
      of rats after 3 and 7 days of recovery from 14-day suspension according to the
      Morey - Holton modification of the Ilyin - Novikov procedure. The cell breathing
      parameters were determined with the help of polarography; desmin content was
      measured using the western-blot technique. The results evidence that cell
      breathing intensity subsided during 14 days of gravitational unloading, reached
      minimum after 3 days of recovery and regained baseline values after 7 days of
      recovery. Post suspension desmin content did not differ from control values, made
      a significant drop in 3 days and returned to baseline values in 7 days of
      recovery. These data suggest an interdependence between cell breathing and desmin
      content in m. soleus fibers of rats as during gravitation unloading, so in the
      period of recovery.

PMID- 22624481
TI  - [Optimization of the mineral nutrition of plants constituting the phototrophic
      component of closed biological life support systems].
AB  - Applicability of a new substrate for crops cultivation in bioregenerative LSSs
      with a high degree of mass-exchange closure was tested. Optimization of leaf
      cabbage nutrition by supplementing the basic substrate fabricated of plant and
      animal residues with ion-exchange resins proved to have a success.

PMID- 22624482
TI  - Australian Meningococcal Surveillance Programme annual report, 2010.
AB  - In 2010 there were 214 laboratory-confirmed cases of invasive meningococcal
      disease analysed by the National Neisseria Network, a nationwide network of
      reference laboratories. One hundred and twenty-four isolates of Neisseria
      meningitidis from invasive cases of meningococcal disease were available for
      which the phenotypes (serogroup, serotype and serosubtype) and/or genotype and
      antibiotic susceptibility were determined. An additional 90 cases were confirmed
      by non-culture based methods (77 by nucleic acid amplification testing and 13 by
      serology), and where possible, serotyping was determined. Nationally 167 (78%)
      laboratory-confirmed cases, where a serogroup was determined, were infected with
      serogroup B, 16 (7.5%) with serogroup C, 9 (4.2%) with serogroup W135 and 7
      (3.3%) with serogroup Y meningococci. The national total of confirmed cases has
      decreased since 2004, but the number of cases may vary between jurisdictions each
      year. New South Wales had the highest number of recorded cases in 2010. Typical
      primary and secondary disease peaks were observed in those aged 4 years or less
      and in adolescents and young adults respectively. Serogroup B cases predominated
      in all age groups and jurisdictions. The common phenotype circulating in
      Australia continues to be B:15:P1.7, corresponding to the porA genotype P1.7,16
      26. Serogroup C cases were again numerically low, as were serogroups W135 and Y.
      Eighty per cent of all isolates showed decreased susceptibility to the penicillin
      group of antibiotics (minimal inhibitory concentration (MIC) 0.06-0.5 mg/L). All
      isolates remained susceptible to ceftriaxone. One isolate had reduced
      susceptibility to ciprofloxacin, and none to rifampicin.

PMID- 22624483
TI  - Australian Gonococcal Surveillance Programme annual report, 2010.
AB  - The Australian Gonococcal Surveillance Programme monitors antibiotic
      susceptibility testing of Neisseria gonorrhoeae isolated in all states and
      territories. In 2010 the in vitro susceptibility of 3,997 isolates of gonococci
      from public and private sector sources was determined by standardised methods.
      Varying antibiotic susceptibility patterns were again reported across
      jurisdictions and regions. Resistance to the penicillins nationally was 29% and,
      with the exception of the Northern Territory, ranged from 22% in Queensland to
      42% in Victoria. Quinolone resistance, most at high minimal inhibitory
      concentration (MIC) levels, was 35% nationally (excepting the Northern
      Territory), ranging from 28% in Queensland to 44% in Victoria. Decreased
      susceptibility to ceftriaxone (MIC 0.06 mg/L or more), was found nationally in
      4.8% of isolates. There has not been an isolate of N. gonorrhoeae with an MIC
      value greater than 0.125 mg/L reported in Australia. Nationally, all isolates
      remained sensitive to spectinomycin. Azithromycin surveillance was performed in
      New South Wales, Queensland, Western Australia, the Northern Territory and South
      Australia, and resistance was found in low numbers of gonococci with MIC values
      up to 16 mg/L. In larger urban centres the ratio of male to female cases was
      high, and rectal and pharyngeal isolates were common in men. In other centres,
      and in rural Australia, the male to female ratio of cases was lower, and most
      isolates were from the genital tract.

PMID- 22624484
TI  - Antimicrobial susceptibility of Staphylococcus aureus isolated from hospital
      inpatients, 2009: report from the Australian Group on Antimicrobial Resistance.
AB  - In 2009, the Australian Group on Antimicrobial Resistance (AGAR) conducted a
      period-prevalence survey of clinical Staphylococcus aureus isolated from hospital
      inpatients. Thirty medical microbiology laboratories from each state and mainland
      territory participated. Specimens were collected more than 48 hours post
      admission. Isolates were tested by Vitek2 (AST-P579 card) and by Etest for
      daptomycin. Nationally, the proportion of S. aureus that were MRSA was 33.6%,
      ranging from 27.3% in South Australia to 41.4% in New South Wales/Australian
      Capital Territory. Resistance to the non-beta-lactam antimicrobials was common
      except for rifampicin, fusidic acid, daptomycin and high-level mupirocin. No
      resistance was detected for vancomycin, teicoplanin, quinupristin-dalfopristin or
      linezolid. Resistance in the methicillin susceptible S. aureus (MSSA) was rare
      apart from erythromycin (12%) and absent for vancomycin, teicoplanin, daptomycin,
      quinupristin-dalfopristin and linezolid. The proportion of methicillin resistant
      S. aureus (MRSA) has remained stable since the first AGAR inpatient survey in
      2005 yet during the same time frame resistance to many antimicrobials, in
      particular tetracycline, trimethoprim-sulphamethoxazole and gentamicin, has
      significantly decreased. This suggests that non-multi-resistant community
      associated MRSA (CA-MRSA) clones are becoming more common in the hospital setting
      and replacing the long-established multi-resistant clones such as ST239-III (Aus
      2/3 EMRSA). Given hospital outbreaks of CA-MRSA are thought to be extremely rare
      it is most likely that patients colonised at admission with CA-MRSA have become
      infected with the colonising strain during their hospital stay.

PMID- 22624485
TI  - Australian Paediatric Surveillance Unit annual report, 2010.

PMID- 22624486
TI  - Communicable diseases surveillance.

PMID- 22624487
TI  - Annual report: surveillance of adverse events following immunisation in
      Australia, 2010.
AB  - This report summarises Australian passive surveillance data for adverse events
      following immunisation (AEFI) reported to the Therapeutic Goods Administration
      (TGA) for 2010, and describes reporting trends over the 11-year period 2000 to
      2010. There were 3,894 AEFI records for vaccines administered in 2010, the
      highest number reported in any year, and a 63% increase over the 2,396 in 2009.
      The increase was almost entirely attributable to the large number of reports
      following seasonal influenza (n = 2,354) and pandemic H1N1 (pH1N1) influenza
      vaccines (n = 514). In children < 7 years of age, the number of reports following
      influenza vaccine increased almost 100-fold from 17 in 2009 to 1,693 in 2010 and,
      for people aged > or =18 years, from 135 to 496. For seasonal influenza vaccine,
      a disproportionate number of reports were from Western Australia (34%),
      consistent with more widespread influenza vaccination of children in that state,
      and 79% were identified as being associated with Fluvax or Fluvax junior (CSL
      Biotherapies). For pH1N1 vaccine, the number of reports in children < 7 years of
      age increased from 23 in 2009 to 329 in 2010, but was available for this age
      group for only 1 month (December) in 2009. In those aged > or = 18 years, for
      whom the pH1N1 vaccine was available from late September 2009, pH1N1 vaccine
      reports decreased from 1,209 in 2009 to 109 in 2010. For influenza vaccines, 79%
      of reports included fever, 45% allergic reactions and 15% malaise. In children
      aged < 7 years, there were 169 reports of convulsions (127 febrile), compared
      with 19 in 2009. In contrast, for non-influenza vaccines, reporting rates in
      children < 7 years of age increased only marginally from 14.1 per 100,000 in 2009
      to 19.3 per 100,000 in 2010. Four deaths temporally associated with immunisation
      were reported but none were considered to have a causal association.

PMID- 22624488
TI  - Australian Rotavirus Surveillance Program annual report, 2010/11.
AB  - The Australian Rotavirus Surveillance Program together with collaborating
      laboratories Australia-wide conducts a laboratory based rotavirus surveillance
      program. This report describes the genotypes of rotavirus strains responsible for
      the hospitalisation of children with acute gastroenteritis during 1 July 2010 to
      30 June 2011. This report represents the fourth year of surveillance following
      introduction of rotavirus vaccines into the National Immunisation Program. One
      thousand one hundred and twenty-seven faecal samples were referred to the centre
      for G and P genotype analysis using hemi-nested multiplex reverse transcription
      polymerase chain reaction. Eight hundred and sixteen samples were confirmed as
      rotavirus positive. Of these, 551 were collected from children under 5 years of
      age, while 265 were from older children and adults. Genotype analysis revealed
      that a change in the dominant type occurred in this reporting period, such that
      genotype G2P[4] was the dominant type nationally, representing 51% of samples,
      followed by genotype G1P[8] (26.1%). Genotypes G3P[8] represented 11% of samples
      while G4P[8] re-emerged as an important genotype, and was identified in 6% of
      samples. Uncommon rotavirus G and P combinations continue to be identified, with
      G2P[8] and G9P[4] identified during this survey. Differences in genotype
      distribution based on vaccine usage continue to be evident in Australian states.
      This survey continues to highlight the fluctuations in rotavirus genotypes, with
      an annual change in dominant genotypes suggesting a more dynamic wild-type
      population.

PMID- 22624489
TI  - Flutracking weekly online community survey of influenza-like illness annual
      report, 2010.
AB  - Flutracking is a national weekly online survey of influenza-like illness (ILI)
      completed by community members. Flutracking integrates participants' ILI symptom
      information with their influenza vaccination status to monitor influenza activity
      and field vaccine effectiveness (FVE). This report summarises results from the
      2010 Flutracking season compared with previous seasons. Nationally, participation
      in Flutracking has more than doubled between 2008 and 2010, with 5,346 new
      participants enrolled or recruited in 2010 and a peak weekly participation of
      10,773. By the end of the 2010 season, 5,904 of 9,109 (64.8%) participants had
      received the monovalent pandemic vaccine and/or the 2010 seasonal vaccine. From
      2007 to 2010 FVE calculations demonstrated that the seasonal vaccine was
      effective except in 2009 during the pandemic. Peak 2010 ILI activity occurred in
      early June and August, and peak weekly 2010 ILI rates (4.2% among unvaccinated
      participants) were lower than the peak ILI rates during the 2009 pandemic (6.0%
      among unvaccinated participants). However, the decrease in laboratory
      notifications was much larger than the decrease in Flutracking rates. In summary,
      the number of Flutracking participants continued to steadily increase over the
      2010 influenza season. The system has shown value in providing weekly vaccination
      uptake data during and beyond the 2009 influenza pandemic, as well as rapid FVE
      estimates that are qualitatively aligned with findings from other analyses of
      vaccine efficacy. Flutracking has also provided estimates of weekly community ILI
      activity that were not biased by health seeking behaviour and clinician testing
      practices.

PMID- 22624490
TI  - Surveillance of adverse events following immunisation: the model of SAEFVIC,
      Victoria.
AB  - State-based adverse events following immunisation (AEFI) reporting systems in
      Australia demonstrate marked regional differences in surveillance methodologies
      and reporting rates. To improve AEFI services in Victoria, Surveillance of
      Adverse Events Following Vaccination in the Community (SAEFVIC) was established
      in 2007. SAEFVIC comprises a central reporting enhanced passive surveillance
      system integrated with clinical services. AEFI may be reported by phone, fax or
      on-line. Immunisation nurse specialists follow up all reports, coupled with
      physician review as required. Supervised re-vaccination in a hospital
      environment, when appropriate, helps ensure clinical support for vaccinees,
      families and health-care providers. The Brighton Collaboration, the Australian
      Immunisation Handbook and in-house case definitions are used to categorise AEFI
      reports. In the first 3 years (2007-2010) of operation 3,265 reports were
      received, describing 4,293 AEFI. The number of reports received increased
      annually over the 3-year period. Seventy-six per cent of AEFI met one of 52
      established case definitions and the remainder were recorded verbatim: 22% of
      reported AEFI were considered severe. Of 1,086 persons reporting an AEFI in 2009,
      356 (36%) attended for a clinical consultation and 325 (83%) were revaccinated,
      of which 114 were day stay or overnight patients. Enhanced passive AEFI
      surveillance using integrated clinical services has been shown to improve adverse
      event reporting with reporting rates in Victoria increasing from 2.6 per 100,000
      in 2003 to 13.5 per 100,000 per annum in 2009. This report describes the SAEFVIC
      service model and summarises outcomes and lessons learnt in the first 3 years of
      operation.

PMID- 22624491
TI  - Campylobacter outbreaks associated with poultry liver dishes.

PMID- 22624492
TI  - OzFoodNet quarterly report, 1 January to 31 March 2011.

PMID- 22624494
TI  - Communicable diseases surveillance.

PMID- 22624493
TI  - OzFoodNet quarterly report, 1 April to 30 June 2011.

PMID- 22624495
TI  - Three-dimensional tracking of carbon nanotubes within living cells.
AB  - Three-dimensional tracking of single-walled carbon nanotubes (SWNT) with an
      orbital tracking microscope is demonstrated. We determine the viscosity regime
      (above 250 cP) at which the rotational diffusion coefficient can be used for
      length estimation. We also demonstrate SWNT tracking within live HeLa cells and
      use these findings to spatially map corral volumes (0.27-1.32 MUm(3)), determine
      an active transport velocity (455 nm/s), and calculate local viscosities (54-179
      cP) within the cell. With respect to the future use of SWNTs as sensors in living
      cells, we conclude that the sensor must change the fluorescence signal by at
      least 4-13% to allow separation of the sensor signal from fluctuations due to
      rotation of the SWNT when measuring with a time resolution of 32 ms.

PMID- 22624496
TI  - Hexanuclear copper(II) cages built on a central {MU3-O...H...MU3-O} moiety, 1,3
      bis(dimethylamino)-2-propanolato and capping R-phosphonates: crystal structures,
      magnetic behavior, and DFT studies.
AB  - The syntheses, structural characterization, and magnetic behavior of two new
      hexanuclear copper(II) complexes derived from R-phosphonic acids and 1,3
      bis(dimethylamino)-2-propanol (Hbdmap) with formulas [Cu(6)(MU-bdmap)(3)(MU(3)-Ph
      PO(3))(2)(MU(3)-O...H...MU(3)-O)(ClO(4))(2)(H(2)O)].5H(2)O (1) and [Cu(6)(MU
      bdmap)(3)(MU(3)-t-Bu-PO(3))(2)(MU(3)-O...H...MU(3)-O)(MU(1,3)
      dca)(dca)(H(2)O)].6H(2)O (2) (Ph-H(2)PO(3) = phenylphosphonic acid, t-Bu
      H(2)PO(3) = tert-butylphosphonic acid, dca = dicyanamide) are reported. Compounds
      1 and 2 are hexanuclear 3.111 R-phosphonate(2-)/1,3-bis(dimethylamino)-2
      propanolato(1-) cages including in the center the [MU(3)-O...H...MU(3)-O](3-)
      unit. The temperature dependence of the magnetic properties of 1 and 2 clearly
      indicates an overall strong antiferromagnetic coupling confirmed by DFT
      calculations.

PMID- 22624497
TI  - Melanoma of the sellar region mimicking pituitary adenoma.
AB  - We report here the case of an 82-year-old woman who presented with visual
      disturbance. MRI demonstrated a sellar mass. The diagnosis of pituitary adenoma
      was made. She underwent transnasal surgery. Histologic, immunohistochemical and
      ultrastructural studies indicated that the tumor was a melanoma. Despite an
      exhaustive search for a primary lesion elsewhere, none was found. The sellar
      tumor was considered a primary lesion, although extrasellar primary tumor imaging
      cannot be excluded with 100% certainty. Reported examples of melanoma affecting
      the sellar region are few. They exhibit morphologic features identical to those
      of melanomas arising elsewhere. Although very rare, primary melanomas enter into
      the differential diagnosis of sellar lesions.

PMID- 22624499
TI  - Geometrical shape of micelles formed by cationic dimeric surfactants determined
      with small-angle neutron scattering.
AB  - The influence of spacer group on the geometrical shape of micelles formed by
      quaternary-bis dimeric (Gemini) surfactants
      C(12)H(25)N(CH(3))(2)(CH(2))(s)N(CH(3))(2)C(12)H(25) (12-s-12) has been
      investigated with small-angle neutron scattering (SANS). Dimeric surfactants with
      a short spacer unit (12-3-12 and 12-4-12) are observed to form elongated general
      ellipsoidal micelles with half axes a < b < c, whereas SANS data demonstrate that
      12-s-12 surfactants with 6 <= s <= 12 form rather small spheroidal micelles
      rather than strictly spherical micelles. By means of comparing our present SANS
      results with previously determined growth rates using time-resolved fluorescence
      quenching, we are able to conclude that micelles formed by 12-6-12, 12-8-12, 12
      10-12, and 12-12-12 are shaped as oblate rather than prolate spheroids. As a
      result, our present investigation suggests a never before reported structural
      behavior of Gemini surfactant micelles, according to which micelles transform
      from elongated ellipsoids to nonelongated oblate spheroids as the length of the
      spacer group is increased. The aggregation number of oblate micelles is observed
      to monotonously decrease with an increasing length of the surfactant spacer
      group, mainly as a result of a decreasing minor half axis (a), whereas the major
      half axis (b) is rather constant with respect to s. We argue that geometrically
      heterogeneous elongated micelles are formed by dimeric surfactants with a short
      spacer group mainly as a result of the surface charges becoming less uniformly
      distributed over the micelle interface. As the length of the spacer group
      increases, the distance between intramolecular charges become approximately equal
      to the average distance between charges on the micelle interface, and as a
      result, rather small oblate spheroidal micelles with a more uniform distribution
      of surface charges are formed by dimeric 12-s-12 surfactants with 6 <= s <= 12.

PMID- 22624498
TI  - Phylogeny of the order Tintinnida (Ciliophora, Spirotrichea) inferred from small-
      and large-subunit rRNA genes.
AB  - Concatenated sequences of small- and large-subunit rRNA genes were used to infer
      the phylogeny of 29 species in six genera of Tintinnida. We confirmed previous
      results on the positions of major clusters and the grouping of various genera,
      including Stenosemella, the paraphyletic Tintinnopsis, the newly investigated
      Helicostomella, and some species of the polyphyletic Favella. Tintinnidium and
      Eutintinnus were found to be monophyletic. This study contributes to tintinnid
      phylogenetic reconstruction by increasing both the number of species and the
      range of genetic markers analyzed.

PMID- 22624500
TI  - alpha7 nicotinic acetylcholine receptor-mediated neuroprotection against
      dopaminergic neuron loss in an MPTP mouse model via inhibition of astrocyte
      activation.
AB  - BACKGROUND: Although evidence suggests that the prevalence of Parkinson's disease
      (PD) is lower in smokers than in non-smokers, the mechanisms of nicotine-induced
      neuroprotection remain unclear. Stimulation of the alpha7 nicotinic acetylcholine
      receptor (alpha7-nAChR) seems to be a crucial mechanism underlying the anti
      inflammatory potential of cholinergic agonists in immune cells, including
      astrocytes, and inhibition of astrocyte activation has been proposed as a novel
      strategy for the treatment of neurodegenerative disorders such as PD. The
      objective of the present study was to determine whether nicotine-induced
      neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse
      model occurs via alpha7-nAChR-mediated inhibition of astrocytes. METHODS: Both in
      vivo (MPTP) and in vitro (1-methyl-4-phenylpyridinium ion (MPP+) and
      lipopolysaccharide (LPS)) models of PD were used to investigate the role(s) of
      and possible mechanism(s) by which alpha7-nAChRs protect against dopaminergic
      neuron loss. Multiple experimental approaches, including behavioral tests,
      immunochemistry, and stereology experiments, astrocyte cell cultures, reverse
      transcriptase PCR, laser scanning confocal microscopy, tumor necrosis factor
      (TNF)-alpha assays, and western blotting, were used to elucidate the mechanisms
      of the alpha7-nAChR-mediated neuroprotection. RESULTS: Systemic administration of
      nicotine alleviated MPTP-induced behavioral symptoms, improved motor
      coordination, and protected against dopaminergic neuron loss and the activation
      of astrocytes and microglia in the substantia nigra. The protective effects of
      nicotine were abolished by administration of the alpha7-nAChR-selective
      antagonist methyllycaconitine (MLA). In primary cultured mouse astrocytes,
      pretreatment with nicotine suppressed MPP(+)-induced or LPS-induced astrocyte
      activation, as evidenced by both decreased production of TNF-alpha and inhibition
      of extracellular regulated kinase1/2 (Erk1/2) and p38 activation in astrocytes,
      and these effects were also reversed by MLA. CONCLUSION: Taken together, our
      results suggest that alpha7-nAChR-mediated inhibition of astrocyte activation is
      an important mechanism underlying the protective effects of nicotine.

PMID- 22624501
TI  - Calmodulin readily switches conformation upon protonating high pKa acidic
      residues.
AB  - We investigate protonation as a possible route for triggering conformational
      change in proteins by focusing on the calmodulin (CaM) example. Two hundred
      nanosecond molecular dynamics (MD) simulations are performed on both the extended
      and compact forms of calcium loaded CaM. The stability of both structures is
      confirmed under prevailing conditions. Protonation of nine acidic residues with
      upshifted pK(a) values leads to a large conformational change in less than 100
      ns. The structure attained is consistent with fluorescence resonance energy
      transfer experimental results as well as structures from an ensemble compatible
      with NMR data. Analysis of the MD trajectories summing up to one microsecond
      implies that the key events leading to the completion of the conformational
      change begins with an initial formation of a salt bridge between the N-lobe and
      the linker, followed by the bending of the C-lobe and the organization of a
      stabilizing hydrophobic patch between the lobes. We find that CaM utilizes its
      Ca(2+) ions to harden/soften different regions so as to achieve various
      conformations. Thus, barrier crossing between extended and compact forms of CaM
      which is normally a rare event due to the repulsive electrostatic interactions
      between the two lobes is facilitated by protonation of high pK(a) residues. The
      results delineate how pH changes might be utilized in the cell to achieve
      different conformation-related functions.

PMID- 22624502
TI  - Impact of low-dose ritonavir on danoprevir pharmacokinetics: results of computer
      based simulations and a clinical drug-drug interaction study.
AB  - BACKGROUND AND OBJECTIVE: Danoprevir, a potent, selective inhibitor of the
      hepatitis C virus (HCV) NS3/4A protease, is metabolized by cytochrome P450 (CYP)
      3A. Clinical studies in HCV patients have shown a potential need for a high
      danoprevir daily dose and/or dosing frequency. Ritonavir, an HIV-1 protease
      inhibitor (PI) and potent CYP3A inhibitor, is used as a pharmacokinetic enhancer
      at subtherapeutic doses in combination with other HIV PIs. Coadministering
      danoprevir with ritonavir as a pharmacokinetic enhancer could allow reduced
      danoprevir doses and/or dosing frequency. Here we evaluate the impact of
      ritonavir on danoprevir pharmacokinetics. METHODS: The effects of low-dose
      ritonavir on danoprevir pharmacokinetics were simulated using Simcyp, a
      population-based simulator. Following results from this drug-drug interaction
      (DDI) model, a crossover study was performed in healthy volunteers to investigate
      the effects of acute and repeat dosing of low-dose ritonavir on danoprevir single
      dose pharmacokinetics. Volunteers received a single oral dose of danoprevir 100
      mg in a fixed sequence as follows: alone, and on the first day and the last day
      of 10-day dosing with ritonavir 100 mg every 12 hours. RESULTS: The initial DDI
      model predicted that following multiple dosing of ritonavir 100 mg every 12 hours
      for 10 days, the danoprevir area under the plasma concentration-time curve (AUC)
      from time zero to 24 hours and maximum plasma drug concentration (C(max)) would
      increase by about 3.9- and 3.2-fold, respectively. The clinical results at day 10
      of ritonavir dosing showed that the plasma drug concentration at 12 hours
      postdose, AUC from time zero to infinity and C(max) of danoprevir increased by
      approximately 42-fold, 5.5-fold and 3.2-fold, respectively, compared with
      danoprevir alone. The DDI model was refined with the clinical data and
      sensitivity analyses were performed to better understand factors impacting the
      ritonavir-danoprevir interaction. CONCLUSION: DDI model simulations predicted
      that danoprevir exposures could be successfully enhanced with ritonavir
      coadministration, and that a clinical study confirming this result was warranted.
      The clinical results demonstrate that low-dose ritonavir enhances the
      pharmacokinetic profile of low-dose danoprevir such that overall danoprevir
      exposures can be reduced while sustaining danoprevir trough concentrations.

PMID- 22624528
TI  - Episodic blindness and ataxia in a horse with cholesterinic granulomas.
AB  - An 11-year-old Oldenburg mare presented following three episodes of acute,
      transient blindness, ataxia, and disorientation within the preceding 7 months.
      Clinical improvement, including return of vision, occurred within 1 week of
      initiating corticosteroid therapy for each of the three episodes. However, mild
      right-sided miosis was a consistent finding on ophthalmic examinations. Routine
      clinicopathologic testing revealed no significant abnormalities, and testing of
      cerebral spinal fluid for selected infectious diseases was unrewarding. Computed
      tomography of the brain demonstrated a hyperattenuating mass with peripheral
      mineralization in the rostroventral aspect of each lateral ventricle. The mare
      was euthanized due to a guarded to poor prognosis. On histopathology, the masses
      consisted of clusters of cholesterol clefts admixed with leukocytes, mineral
      deposits, and connective tissue. Cholesterinic granulomas of the lateral
      ventricles and hydrocephaly were diagnosed. Cholesterinic granulomas should be
      considered a differential diagnosis in horses presenting for intermittent
      blindness.

PMID- 22624503
TI  - Population pharmacokinetics and pharmacogenetics of everolimus in renal
      transplant patients.
AB  - BACKGROUND AND OBJECTIVE: Everolimus is a novel macrolide immunosuppressant used
      in the prevention of acute and chronic rejection of solid organ transplants.
      Everolimus is being actively investigated worldwide as a non-nephrotoxic
      alternative for calcineurin inhibitors. Its highly variable pharmacokinetics and
      narrow therapeutic window make it difficult to maintain an adequate exposure to
      prevent serious adverse effects. The primary objective of this study was to
      improve prediction of everolimus systemic exposure in renal transplant patients
      by describing the pharmacokinetics of everolimus and identifying the influence of
      demographic factors and a selection of polymorphisms in genes coding for ABCB1,
      CYP3A5, CYP2C8 and PXR. The secondary objective of this study was to develop a
      limited sampling strategy to enable prediction of everolimus exposure in an
      efficient way and to compare it with the widely used trough blood concentration
      (C(trough)) monitoring. METHODS: A total of 783 blood samples were obtained from
      53 renal transplant patients who had been switched from a triple therapy of
      ciclosporin, mycophenolate mofetil and prednisolone to a calcineurin inhibitor
      free dual therapy of everolimus (twice daily) and prednisolone. Everolimus blood
      concentrations were analysed in whole blood using liquid chromatography-tandem
      mass spectrometry during routine therapeutic drug monitoring targeting an area
      under the blood concentration-time curve from time zero to 12 hours (AUC(12)) of
      120 MUg . h/L. A population pharmacokinetic model was developed and demographic
      factors and genetic polymorphisms in genes coding for ABCB1, CYP3A5, CYP2C8 and
      PXR were included as covariates. In addition, a limited sampling strategy was
      developed. RESULTS: Maintaining everolimus systemic exposure at an AUC(12) of 120
      MUg . h/L resulted in low rejection rates but considerable numbers of adverse
      events and toxicity. Everolimus pharmacokinetics were best described by a two
      compartment model with lag-time (oral clearance = 17.9 L/h; volume of
      distribution of the central compartment after oral administration [V(1)/F] = 148
      L and first-order absorption rate constant [k(a)] = 7.36 h-1). Ideal body weight
      was significantly related to V(1)/F. None of the selected polymorphisms in genes
      coding for enzymes involved in distribution and metabolism of everolimus had a
      significant influence on everolimus pharmacokinetics. The pharmacokinetic limited
      sampling model (C(trough) and whole blood drug concentration at 2 hours postdose
      [C(2)]) resulted in a significantly improved prediction of everolimus exposure
      compared with the widely used C(trough) monitoring. CONCLUSION: A two-compartment
      pharmacokinetic model with lag-time describing the concentration-time profile of
      oral everolimus in renal transplant patients has been developed using
      pharmacokinetic modelling. Ideal body weight significantly influenced V(1)/F of
      everolimus; however, the selected polymorphisms in genes coding for ABCB1,
      CYP3A5, CYP2C8 and PXR had no clinically relevant effect on everolimus
      pharmacokinetics. Everolimus C(trough) and C(2) as a limited sampling model can
      be used to accurately estimate everolimus systemic exposure, an improvement over
      the widely used C(trough) monitoring.

PMID- 22624529
TI  - Subsidising patient dispensing fees: the cost of injecting equity into the opioid
      pharmacotherapy maintenance system.
AB  - INTRODUCTION AND AIMS: Australian pharmacotherapy maintenance programs incur
      costs to patients. These dispensing fees represent a financial burden to patients
      and are inconsistent with Australian health-care principles. No previous work has
      examined the current costs nor the future predicted costs if government
      subsidised dispensing fees. DESIGN AND METHODS: A system dynamics model, which
      simulated the flow of patients into and out of methadone maintenance treatment,
      was developed. Costs were imputed from existing research data. The approach
      enabled simulation of possible behavioural responses to a fee subsidy (such as
      higher retention) and new estimates of costs were derived under such scenarios.
      RESULTS: Current modelled costs (AUS$11.73m per month) were largely borne by
      state/territory government (43%), with patients bearing one-third (33%) of the
      total costs and the Commonwealth one-quarter (24%). Assuming no behavioural
      changes associated with fee subsidies, the cost of subsidising the dispensing
      fees of Australian methadone patients would be $3.9m per month. If retention were
      improved as a result of fee subsidy, treatment numbers would increase and the
      model estimates an additional cost of $0.8m per month. If this was coupled with
      greater numbers entering treatment, the costs would increase by a further $0.4m
      per month. In total, full fee subsidy with modelled behavioural changes would
      increase per annum government expenditure by $81.8m to $175.8m. DISCUSSION AND
      CONCLUSIONS: If government provided dispensing fee relief for methadone
      maintenance patients, it would be a costly exercise. However, these additional
      costs are offset by the social and health gains achieved from the methadone
      maintenance program.

PMID- 22624530
TI  - Barriers to condom use among women at risk of HIV/AIDS: a qualitative study from
      Iran.
AB  - BACKGROUND: The growing trend of women infected with HIV through sexual
      transmission is alarming. Factors influencing condom use have not yet been fully
      identified, especially in countries with conservative cultures and backgrounds.
      The present study aimed to explore the barriers of condom use in Iranian women at
      risk of HIV. METHODS: Using the grounded theory methodology, participants'
      experiences and their perceptions regarding condom were collected during semi
      structured in depth interviews. Participants were 22 women, aged 21-49 years,
      considered to be at risk for HIV, due to their own or their partner's sexual
      behaviors. Qualitative analysis of the data was conducted manually and was guided
      by constant comparative analysis. RESULTS: Two main barriers, personal and socio
      environmental emerged from data analysis. Lack of perceived threat, absence of
      protective motivation, inadequate knowledge, perceived lack of control, negative
      attitudes towards condom and misperception were the major personal barriers,
      while unsupportive environments and cultural norms were the common socio
      environmental barriers to condom use among these at risk women. CONCLUSIONS:
      These critical barriers have to be addressed for implementing effective
      prevention programs against HIV among populations at risk for HIV.

PMID- 22624531
TI  - Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4
      vs. 0.9% NaCl fluid replacement in patients with severe sepsis: the CRYSTMAS
      study.
AB  - INTRODUCTION: Inadequate initial treatment and delayed hemodynamic stabilization
      (HDS) may be associated with increased risk of death in severe sepsis patients.
      METHODS: In order to compare the hemodynamic efficacy and safety of 6% HES
      130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a
      prospective, multicenter, active-controlled, double-blind, randomized study in
      intensive care units. RESULTS: 174 out of 196 patients reached HDS (88 and 86
      patients for HES and NaCl, respectively). Significantly less HES was used to
      reach HDS vs. NaCl (1,379 +/- 886 ml in the HES group and 1,709 +/- 1,164 ml in
      the NaCl group (mean difference = -331 +/- 1,033, 95% CI -640 to -21, P =
      0.0185). Time to reach HDS was 11.8 10.1 hours vs. 14.3 +/- 11.1 hours for HES
      and NaCl, respectively. Total quantity of study drug infused over four
      consecutive days, ICU and hospital LOS, and area under the curve of SOFA score
      were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients
      for HES and NaCl, respectively (P = 0.454). There was no difference between AKIN
      and RIFLE criteria among groups and no difference in mortality, coagulation, or
      pruritus up to 90 days after treatment initiation. CONCLUSION: Significantly less
      volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid
      resuscitation in severe sepsis patients without any difference for adverse events
      in both groups. CLINICALTRIALSGOV: NCT00464204.

PMID- 22624533
TI  - The need for continued ethical scrutiny.

PMID- 22624532
TI  - Alterations of platelet function and clot formation kinetics after in vitro
      exposure to anti-A and -B.
AB  - BACKGROUND: ABO-mismatched platelets (PLTs) are commonly transfused despite
      reported complications. We hypothesized that because PLTs possess A and B
      antigens on their surface, ABO-mismatched transfused or recipient PLTs could
      become activated and/or dysfunctional after exposure to anti-A or -B in the
      transfused or recipient plasma. We present here in vitro modeling data on the
      functional effects of exposure of PLTs to ABO antibodies. STUDY DESIGN AND
      METHODS: PLT functions of normal PLTs of all ABO types were assessed before and
      after incubation with normal saline, ABO-identical plasma samples, or O plasma
      samples with varying titers of anti-A and anti-B (anti-A/B). Assays used for this
      assessment include PLT aggregation, clot kinetics, thrombin generation, PLT
      cytoskeletal function, and mediator release. RESULTS: Exposure of antigen-bearing
      PLTs to O plasma with moderate to high titers of anti-A/B significantly inhibits
      aggregation, prolongs PFA-100 epinephrine closure time, disrupts clot formation
      kinetics, accelerates thrombin generation, reduces total thrombin production,
      alters PLT cytoskeletal function, and influences proinflammatory and
      prothrombotic mediator release. CONCLUSIONS: Our findings demonstrate a wide
      range of effects that anti-A/B have on PLT function, clot formation, thrombin
      generation, PLT cytoskeletal function, and mediator release. These data provide
      potential explanations for clinical observations of increased red blood cell
      utilization in trauma and surgical patients receiving ABO-nonidentical blood
      products. Impaired hemostasis caused by anti-A/B interacting with A and B
      antigens on PLTs, soluble proteins, and perhaps even endothelial cells is a
      potential contributing factor to hemorrhage in patients receiving larger volumes
      of ABO-nonidentical transfusions.

PMID- 22624534
TI  - Racial/ethnic health disparities and ethics -- the need for a multilevel
      approach.

PMID- 22624535
TI  - Redistribution and recognition -- pursuing social justice in public health.

PMID- 22624536
TI  - Debating the cause of health disparities -- implications for bioethics and racial
      equality.

PMID- 22624537
TI  - Elderly and older racial/ethnic minority healthcare inequalities -- care,
      solidarity, and action.

PMID- 22624538
TI  - African American and white disparities in pediatric kidney transplantation in the
      United States -- unfortunate or unjust?

PMID- 22624539
TI  - Postcolonial bioethics -- a lens for considering the historical roots of racial
      and ethnic inequalities in mental health.

PMID- 22624540
TI  - The Irish Council for Bioethics -- an unaffordable luxury?

PMID- 22624541
TI  - Regulating ethics in Australian healthcare research.

PMID- 22624542
TI  - Introduction -- a modern version of an ancient question.

PMID- 22624543
TI  - Must I stay? -- the obligations of physicians in proximity to the Fukushima
      Nuclear Power Plant.

PMID- 22624544
TI  - The case: Starving for perfection.

PMID- 22624545
TI  - Commentary: Staying the swinging pendulum.

PMID- 22624546
TI  - Commentary: Where ignorant armies clash by night.

PMID- 22624547
TI  - Commentary: Practical wisdom and theory.

PMID- 22624548
TI  - What actually happened.

PMID- 22624549
TI  - BioCEP - a model educational program for cross-cultural bioethics.

PMID- 22624550
TI  - Laxiflorolides A and B, epimeric bishomoditerpene lactones from Isodon eriocalyx.
AB  - Laxiflorolides A (1) and B (2), two unprecedented epimeric bishomoditerpene
      lactones with a unique C(22) framework, along with laxiflorins P-R (3-5),
      maoecrystal P (6), maoecrystal C (7), and eriocalyxin B (8), were isolated from
      the leaves of I. eriocalyx var. laxiflora. The structures of 1 and 2, including
      the absolute configurations, were determined by spectroscopic methods and single
      crystal X-ray diffraction analysis. All of the compounds isolated were evaluated
      for their cytotoxicity against five tumor cell lines. Compounds 3, 6, and 8
      showed remarkable cytotoxic activity against certain cell lines compared with the
      positive control.

PMID- 22624551
TI  - Recent developments in gastroesophageal reflux disease and Barrett's esophagus:
      ANNO 2012.
AB  - The incidence of gastroesophageal reflux disease (GERD) and esophageal columnar
      metaplasia is rising worldwide. Both mechanical and functional factors perturb
      the double sphincter barrier at the esophagogastric junction (EGJ). Discovery of
      the acid pocket is fundamental in understanding postprandial acid reflux. Adding
      impedencemetry to pH measurements allows detection of non-acid or weakly acidic
      reflux. Histologic and endoscopic injury of the squamous mucosa rises from
      dilation of the intercellular spaces, papillary extension, accentuated
      intrapapillary looping, red streaks, erosive tissue loss, etc., graded with the
      Los Angeles system. Seventy percent of patients have no recognizable
      abnormalities (non-erosive or neGERD). Treatment of GERD mainly relates to the
      control of acid secretion but a revival of alginate/antacid obliterating the acid
      pocket is to be expected. Weaker heartburn control in neGERD is a misnomer
      because most studies included patients with no evidence of reflux disease.
      Traditional (delayed-release) proton pump inhibitors (PPIs) are powerful
      suppressors of acid secretion but do have limitations such as gradual build up of
      acid control, weak control of nocturnal acid recovery, possibility of rebound,
      occasional need for dose escalation, etc. Barrett's esophagus (BE) is
      endoscopically diagnosed also in the absence of intestinal metaplasia. A
      prerequisite is the precise location of the EGJ (proximal end of gastric folds,
      esophageal sphincter pinch, distal extent of palisade vessels). BE is graded with
      the Prague C & M system. Barrett's cancer develops usually via low-grade and high
      grade dysplasia. Endoscopic examination may indicate suspicious areas, amenable
      for targeted biopsy. Otherwise, four quadrant biopsies are obtained when
      searching for neoplasia. Low-grade dysplasia, especially when it is multifocal
      and p53 positive, high-grade dysplasia and mucosal cancer should be treated with
      endoscopic resection of the target area, followed by radiofrequency ablation of
      the adjacent non-neoplastic columnar mucosa, followed with powerful acid
      suppressant therapy. The long-term results of the combination of resection and
      ablation are exiting and at least comparable to surgical resection.

PMID- 22624552
TI  - Prevalence and endoscopic features of eosinophilic esophagitis in patients with
      esophageal or upper gastrointestinal symptoms.
AB  - OBJECTIVE: This study was aimed to evaluate the prevalence of eosinophilic
      esophagitis (EoE) among patients with esophageal or upper gastrointestinal (UGI)
      symptoms. METHODS: Patients with esophageal or UGI symptoms including dysphagia
      food impaction, acid regurgitation, heartburn, chest pain, epigastric pain,
      nausea and/or vomiting were prospectively collected. The enrolled patients
      responded to a symptomatic questionnaire and underwent an
      esophagogastroduodenoscopy and esophageal biopsies. Supportive endoscopic
      findings of EoE (ring-like appearance, liner furrows, whitish papules, shearing
      or friability) were recorded. EoE was diagnosed if patients had chronic UGI or
      esophageal symptoms, the esophageal biopsy showed >=15 eosinophils/high-power
      field and were unresponsive to 2-3 weeks of proton pump inhibitors. RESULTS: A
      total of 122 patients were enrolled and supportive endoscopic findings were found
      in 31 (25.4%) patients [whitish papules: 19 (15.6%), ring-like appearance: 8
      (6.6%), linear furrows: 5 (4.1%)]. One patient had a simultaneous ring-like
      appearance and linear furrows. EoE was diagnosed in 8 (6.6%) patients and
      supportive endoscopic findings and past history of gastroesophageal reflux
      disease, allergic rhinitis and atopic dermatitis were more common in EoE positive
      than EoE negative patients. The diagnostic yield of endoscopic findings was 40.0%
      (2/5) in linear furrows, 25.0% (2/8) in ring-like appearance and 15.8% (3/19) in
      whitish papules. CONCLUSION: Prevalence of EoE among patients with esophageal or
      UGI symptoms was 6.6%. Linear furrows and ring-like appearance had a relatively
      high diagnostic value.

PMID- 22624553
TI  - Prevalence, clinical manifestations and endoscopic features of eosinophilic
      esophagitis: a pathological review in China.
AB  - OBJECTIVE: We aimed to determine the prevalence of eosinophilic esophagitis (EoE)
      and define its clinical and endoscopic characteristics in Chinese patients.
      METHODS: Esophageal specimens obtained from January 2006 to December 2010 in the
      First Affiliated Hospital of Sun Yat-sen University were reviewed, and the data
      on clinical characteristics and endoscopic findings of patients were obtained.
      Patients with eosinophils >=15 per high power field (HPF) were identified as
      having EoE. RESULTS: A total of 12 patients met the criteria for EoE,
      establishing a prevalence of 0.34%. These patients presented with dysphagia
      (4/12, 33.3%), gastroesophageal reflux disease (GERD)-like symptoms (3/12,
      25.0%), abdominal pain (3/12, 25.0%) and others (2/12, 16.7%). The most common
      endoscopic finding was plaques (5/12, 41.7%), and other findings were irregular Z
      line (2/12, 16.7%), erosive esophagitis (2/12, 16.7%), white exudates (1/12,
      8.3%), linear furrows (1/12, 8.3%), Schatzki ring (1/12, 8.3%), ulcers (1/12,
      8.3%) and erythema (1/12, 8.3%). CONCLUSIONS: The prevalence of EoE was 0.34% in
      our patients. Clinicians should pay attention to patients manifested with
      dysphagia and GERD-like symptomes with endosopic findings of white exudates,
      plaques, Schatzki ring and linear furrows.

PMID- 22624554
TI  - Transnasal esophagogastroduodenoscopy for placement of nasoenteric feeding tubes
      in patients with severe upper gastrointestinal diseases.
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of small-caliber transnasal
      esophagogastroduodenoscopy for the placement of nasoenteric feeding tubes (NET)
      in patients with severe upper gastrointestinal (GI) diseases. METHODS: Between
      January 2007 and March 2010, 51 patients underwent transnasal endoscopy for the
      placement of NET in Peking University Third Hospital. Indications for NET
      included esophageal stricture or gastric outlet obstruction because of corrosive
      esophagitis or gastritis, partial obstruction due to malignancy, stenosis in
      stoma or efferent loop, gastroparesis, metallic stent in upper GI tract,
      tracheoesophageal fistula, severe acute pancreatitis, anorexia nervosa and
      intensive care patients. The tubes were endoscopically placed using the guidewire
      technique. The position of the tube was confirmed by the immediate second
      endoscopy or abdominal X-ray. If the initiate placement was not correct, an
      adjustment or a second placement was conducted immediately. RESULTS: Initial post
      pyloric placement of NET was achieved in 43 of 51 patients (84.3%), but the total
      success rate reached 98.0% (50/51) after the second placement. The time required
      for the procedure ranged from 10 to 35 min, with a median time of 20.4 min.
      Epistaxis occurred in 2 patients. There were no complications of hemorrhage,
      perforation or aspiration. CONCLUSION: The transnasal endoscopic placement of NET
      was feasible in patients with upper GI diseases, especially in those with changed
      anatomy.

PMID- 22624555
TI  - Diagnosis and management of jejunoileal diverticular hemorrhage: a decade of
      experience.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical features and
      management of jejunoileal diverticular hemorrhage at Changhua Christian Hospital
      over the past decade. METHODS: A retrospective study on the clinical features,
      treatment and outcomes of the patients with jejunoileal diverticular hemorrhage
      diagnosed from January 2000 to December 2010 was conducted. RESULTS: Twenty-eight
      patients (male to female ratio 15:13) were enrolled in the study with a mean age
      of 73.9 years. Symptoms consisted of bloody stool (46.4%), tarry stool (82.1%),
      coffee ground vomitus (7.1%) and shock (39.3%). The mean duration of hospital
      stay was 13.5 days and the mean blood transfusion volume was 13.5 units. Eight
      patients (28.6%) underwent surgical resection, 9 (32.1%) received endoscopic
      therapy and 11 (39.3%) were administered conservative therapy. Five patients
      (17.9%) had recurrent bleeding during the follow-up. Two patients (7.1%) died
      eventually. CONCLUSIONS: The management of jejunoileal diverticular hemorrhage
      has mainly been nonsurgical at our institution over the past decade. The
      decreased requirement of surgical intervention might be attributed to the
      improvement of diagnostic and treatment procedures during this period.

PMID- 22624556
TI  - Changes of serum biochemical parameters and liver pathology in 18 patients with
      1,1,2,2-tetrachloroethane-induced hepatotoxicity.
AB  - OBJECTIVE: To evaluate the changes of serum biochemical parameters and liver
      pathology in patients with 1,1,2,2-tetrachloroethane (TTCE)-induced
      hepatotoxicity. METHODS: A total of 18 patients were diagnosed as TTCE-induced
      hepatotoxicity with an incubation period of 11-56 days. Blood samples were
      obtained from all patients and liver biopsy was performed in 16. RESULTS: All
      patients had fatigue, poor appetite and dark urine, 15 of whom suffered nausea,
      vomiting, abdominal distension and other gastrointestinal disorders. All patients
      had various degrees of liver function damage, and one died from liver failure.
      The prothrombin time was significantly prolonged in 6 patients. Histological
      findings showed varying degrees of necrosis, fatty degeneration and fibrosis in
      portal areas without cirrhosis. Patients with more severe jaundice had more
      severe pathologic changes, including piecemeal and bridge necrosis, and
      cholestasis. CONCLUSIONS: TTCE-induced hepatotoxicity may cause the changes in
      serum biochemical parameters and liver pathology. Most patients might recover
      with regular treatment. Prevention and early diagnosis of TTCE-induced
      hepatotoxicity are necessary.

PMID- 22624558
TI  - Dyspepsia and gastroesophageal reflux symptoms predominate in gastric
      diverticulum.

PMID- 22624557
TI  - Overexpression of Smad ubiquitin regulatory factor 2 suppresses transforming
      growth factor-beta mediated liver fibrosis.
AB  - OBJECTIVE: To determine the function of Smad ubiquitin regulatory factor 2
      (Smurf2) on the development of liver fibrosis and cirrhosis. METHODS: In vivo
      Smurf2 expression in fibrotic and cirrhotic rat and human liver tissues were
      measured using reverse transcription-polymerase chain reaction, Western blot (WB)
      and immunohistochemistry. In vitro Smurf2 levels were determined in LX-2 cell
      line with or without transforming growth factor (TGF)-beta1 treatment; I, III, IV
      collagen and laminin levels were determined by ELISA. The recombinant plasmid
      pcDNA3.1-Smurf2 was transfected into LX-2 cells, and WB and ELISA were utilized
      to analyze the expression of TGF-beta receptor type I (TbetaRI), Smad7, collagens
      and laminin with or without proteasome inhibitor MG-132. Coimmunoprecipitation
      was utilized to characterize the interactions among these factors and the
      ubiquitination levels. pcDNA3.1-Smad7 vector was transfected and subsequent
      examinations were conducted just as Smurf2. RESULTS: Smurf2 levels were elevated
      in the early period of fibrotic rat liver and TGF-beta1-treated LX-2 cells but
      were reduced in the cirrhotic livers. Smurf2 overexpression in LX-2 cells reduced
      TbetaRI and Smad7 levels, which was accompanied by decreased collagen and laminin
      levels. Coimmunoprecipitation demonstrated that Smurf2 interacted with TbetaRI
      and Smad7, which increased TbetaRI and Smad7 ubiquitin levels. Smad7
      overexpression reduced the TbetaRI level and was accompanied by decreased
      collagen and laminin levels. MG-132 could antagonize these effects. CONCLUSION:
      Smurf2 interacts with Smad7 to suppress TGF-beta-mediated liver fibrosis through
      the ubiquitin-dependent degradation of TbetaRI during the early period of liver
      fibrosis.

PMID- 22624559
TI  - Novel soluble epoxide hydrolase inhibitor protects mitochondrial function
      following stress.
AB  - Epoxyeicosatrienoic acids (EETs) are active metabolites of arachidonic acid that
      are inactivated by soluble epoxide hydrolase enzyme (sEH) to
      dihydroxyeicosatrienoic acid. EETs are known to render cardioprotection against
      ischemia reperfusion (IR) injury by maintaining mitochondrial function. We
      investigated the effect of a novel sEH inhibitor (sEHi) in limiting IR injury.
      Mouse hearts were perfused in Langendorff mode for 40 min and subjected to 20 min
      of global no-flow ischemia followed by 40 min of reperfusion. Hearts were
      perfused with 0.0, 0.1, 1.0 and 10.0 umol.L(-1) of the sEHi N-(2-chloro-4
      methanesulfonyl-benzyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide (BI00611953).
      Inhibition of sEH by BI00611953 significantly improved postischemic left
      ventricular-developed pressure and reduced infarct size following IR compared
      with control hearts, and similar to hearts perfused with 11,12-EETs (1 umol.L(
      1)) and sEH(-/-) mice. Perfusion with the putative EET receptor antagonist 14,15
      epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 10 umol.L(-1)), or the plasma membrane
      K(ATP) channels (pmK(ATP)) inhibitor (glibenclamide, 10 umol.L(-1)) abolished the
      improved recovery by BI00611953 (1 umol.L(-1)). Mechanistic studies in H9c2 cells
      demonstrated that BI0611953 decreased ROS generation, caspase-3 activity,
      proteasome activity, increased HIF-1? DNA binding, and delayed the loss of
      mitochondrial membrane potential (DeltaPsi(m)) caused by anoxia-reoxygenation.
      Together, our data demonstrate that the novel sEHi BI00611953, a nicotinamide
      based compound, provides significant cardioprotection against ischemia
      reperfusion injury.

PMID- 22624560
TI  - The functional significance of E277K and V295A HFE  mutations.
AB  - Hereditary haemochromatosis (HH) is an autosomal recessive disorder characterized
      by excessive intestinal iron absorption resulting in increased pathological body
      iron stores. It is typically associated with homozygosity for the c.845G>A
      (p.C282Y) mutation in the HFE gene. However, other HFE alterations have been
      reported in affected individuals but their association with the disease is
      unclear. This study analysed the functional consequences of two HFE mutations,
      c.829G>A (p.E277K) and c.884T>C (p.V295A). Firstly, it was shown that c.829G>A
      affects the HFE splicing by diminishing the full length HFE and ivs4_66bp
      inclusion transcript levels, while increasing the amount of exon 4 skipping
      transcript. Immunofluorescent techniques showed that the HFE_E277K protein had a
      diffuse distribution (similar to HFE_C282Y) while HFE_V295A presented at the cell
      surface and perinuclear compartments (resembling HFE_wt). Immunoprecipitation
      assays revealed a decreased association of HFE_E277K and HFE_V295A with both
      beta2-microglobulin (B2M; 38 +/- 7% and 66 +/- 8%, respectively) and transferrin
      receptor (TFRC, also termed TFR1) (58 +/- 2% and 49 +/- 16%, respectively).
      Herein, we prove that both mutations partially abrogate HFE association with B2M
      and TFRC, crucial for its correct processing and cell surface presentation.
      Although E277K has a more deleterious effect than V295A, we propose that both
      mutations may play a role in the development of hereditary haemochromatosis.

PMID- 22624561
TI  - Effects of tour boats on dolphin activity examined with sensitivity analysis of
      Markov chains.
AB  - In Patagonia, Argentina, watching dolphins, especially dusky dolphins
      (Lagenorhynchus obscurus), is a new tourist activity. Feeding time decreases and
      time to return to feeding after feeding is abandoned and time it takes a group of
      dolphins to feed increase in the presence of boats. Such effects on feeding
      behavior may exert energetic costs on dolphins and thus reduce an individual's
      survival and reproductive capacity or maybe associated with shifts in
      distribution. We sought to predict which behavioral changes modify the activity
      pattern of dolphins the most. We modeled behavioral sequences of dusky dolphins
      with Markov chains. We calculated transition probabilities from one activity to
      another and arranged them in a stochastic matrix model. The proportion of time
      dolphins dedicated to a given activity (activity budget) and the time it took a
      dolphin to resume that activity after it had been abandoned (recurrence time)
      were calculated. We used a sensitivity analysis of Markov chains to calculate the
      sensitivity of the time budget and the activity-resumption time to changes in
      behavioral transition probabilities. Feeding-time budget was most sensitive to
      changes in the probability of dolphins switching from traveling to feeding
      behavior and of maintaining feeding behavior. Thus, an increase in these
      probabilities would be associated with the largest reduction in the time
      dedicated to feeding. A reduction in the probability of changing from traveling
      to feeding would also be associated with the largest increases in the time it
      takes dolphins to resume feeding. To approach dolphins when they are traveling
      would not affect behavior less because presence of the boat may keep dolphins
      from returning to feeding. Our results may help operators of dolphin-watching
      vessels minimize negative effects on dolphins.

PMID- 22624562
TI  - Relationship between high-fidelity simulation and patient safety in prelicensure
      nursing education: a comprehensive review.
AB  - Advances in nursing simulation technology raise the question "Are educators
      feeling pressure to accommodate the learning styles of the techno-age studentry?"
      This integrative review evaluates the current quantitative evidence from
      preintervention-postintervention and control-experimental research studies
      related to the use of simulation in prelicensure nursing education directed at
      enhancing safety in nursing practice. A thorough review of the available
      literature using truncated search terms in several databases yielded 258
      scholarly, peer-reviewed articles, of which 18 articles directly addressed the
      posed research question related to simulation and safety. Replete with student
      reports of simulation as an enjoyable learning activity, the literature does not
      yet support simulation over other approaches to the teaching-learning of safety
      competencies in nursing. Therefore, nurse educators must continue to select the
      most appropriate methods based on the specific course, student, or program type,
      with concentrated focus on competency-based safety education in nursing.

PMID- 22624563
TI  - Interpreting the NLN Jeffries Framework in the context of Nurse Educator
      preparation.
AB  - The NLN Jeffries Framework describing simulation in nursing education has been
      used widely to guide construction of human patient simulation scenarios and serve
      as a theoretical framework for research on the use of simulation. This framework
      was developed with a focus on prelicensure nursing education. However, use of
      human patient simulation scenarios is also a way of providing practice
      experiences for graduate students learning the educator role. High-fidelity human
      patient simulation offers nurse educator faculty a unique opportunity to
      cultivate the practical knowledge of teaching in an interactive and dynamic
      environment. This article describes how the components of The NLN Jeffries
      Framework can help to guide simulation design for nurse educator preparation.
      Adapting the components of the framework-which include teacher, student,
      educational practices, design characteristics, and outcomes-helps to ensure that
      future faculty gain hands-on experience with nurse educator core competencies.

PMID- 22624564
TI  - Preparing emotionally intelligent doctor of nursing practice leaders.
AB  - The Institute of Medicine (IOM) identified the need for interdisciplinary teams
      that collaborate, communicate, and integrate care across settings to improve
      health care delivery. Focusing on innovative strategies that address leadership
      skills in graduate nursing education could have an effect on interdisciplinary
      partnerships, transformation of patient care, and new styles of leadership to
      change current practice models. In response to the IOM guidelines, we
      incorporated emotional intelligence as a component in our Doctor of Nursing
      Practice (DNP) leadership curriculum. This article describes a new action
      oriented leadership model that prepares the DNP graduate for leadership roles to
      serve the public and the nursing discipline during a time of radical changes in
      health care. Behavioral profile, nontraditional readings, and online discussions
      form the basis of the model. The principles and strategies in this article can be
      applied to nursing education in multiple arenas, at both the undergraduate and
      graduate settings.

PMID- 22624565
TI  - Genetic-basis analysis of heterotic loci in Dongxiang common wild rice (Oryza
      rufipogon Griff.).
AB  - Heterosis is widely used in genetic crop improvement; however, the genetic basis
      of heterosis is incompletely understood. The use of whole-genome segregating
      populations poses a problem for establishing the genetic basis of heterosis, in
      that interactions often mask the effects of individual loci. However,
      introgression line (IL) populations permit the partitioning of heterosis into
      defined genomic regions, eliminating a major part of the genome-wide epistasis.
      In our previous study, based on mid-parental heterosis (HMP) value with single
      point analysis, 42 heterotic loci (HLs) associated with six yield-related traits
      were detected in wild and cultivated rice using a set of 265 ILs of Dongxiang
      common wild rice (Oryza rufipogon Griff.). In this study, the genetic effects of
      HLs were determined as the combined effects of both additive and dominant gene
      actions, estimated from the performance values of testcross F1s and the dominance
      effects estimated from the HMP values of testcross F1s. We characterized the gene
      action type at each HL. Thirty-eight of the 42 HLs were over-dominant, and in the
      absence of epistasis, four HLs were dominant. Therefore, we favour that over
      dominance is a major genetic basis of 'wild-cultivar' crosses at the single
      functional Mendelian locus level.

PMID- 22624566
TI  - Impact of epistasis and QTL * environmental interaction on the mass filling rate
      during seed development of soybean.
AB  - Seed filling rate of soybean has been shown to be a dynamic process in different
      developmental stages affected by both genotype and environment. The objective of
      the present study was to determine additive, epistatic and quantitative trait
      loci (QTLs) * environment interaction (QE) effects of the QTL underlying a seed
      filling rate of soybean. One hundred and forty-three recombinant inbred lines
      (RILs) derived from the cross of Charleston and Dongnong 594 were used with 2
      years of field data (2004 and 2005). Eleven QTLs with significantly unconditional
      and conditional additive (a) effect and/or additive * environment interaction
      (ae) effect at different filling stages were identified. Of them six QTLs showed
      positive a effects and four QTLs had negative a effects on the seed filling rate
      during seed development. aa and aae effects of 12 pairs of QTLs were identified
      by unconditional mapping from the initial stage to the final stage. Thirteen
      pairs of QTLs underlying the seed filling rate with aa and aae effects were
      identified by conditional mapping. QTLs with aa and aae (additive * additive *
      environment) effects appeared to vary at different filling stages. Our results
      demonstrated that the mass filling rate in soybean seed were under genetic and
      environmental control.

PMID- 22624567
TI  - Genome-wide association mapping including phenotypes from relatives without
      genotypes.
AB  - A common problem for genome-wide association analysis (GWAS) is lack of power for
      detection of quantitative trait loci (QTLs) and precision for fine mapping. Here,
      we present a statistical method, termed single-step GBLUP (ssGBLUP), which
      increases both power and precision without increasing genotyping costs by taking
      advantage of phenotypes from other related and unrelated subjects. The procedure
      achieves these goals by blending traditional pedigree relationships with those
      derived from genetic markers, and by conversion of estimated breeding values
      (EBVs) to marker effects and weights. Additionally, the application of mixed
      model approaches allow for both simple and complex analyses that involve multiple
      traits and confounding factors, such as environmental, epigenetic or maternal
      environmental effects. Efficiency of the method was examined using simulations
      with 15,800 subjects, of which 1500 were genotyped. Thirty QTLs were simulated
      across genome and assumed heritability was 0.5. Comparisons included ssGBLUP
      applied directly to phenotypes, BayesB and classical GWAS (CGWAS) with
      deregressed proofs. An average accuracy of prediction 0.89 was obtained by
      ssGBLUP after one iteration, which was 0.01 higher than by BayesB. Power and
      precision for GWAS applications were evaluated by the correlation between true
      QTL effects and the sum of m adjacent single nucleotide polymorphism (SNP)
      effects. The highest correlations were 0.82 and 0.74 for ssGBLUP and CGWAS with
      m=8, and 0.83 for BayesB with m=16. Standard deviations of the correlations
      across replicates were several times higher in BayesB than in ssGBLUP. The
      ssGBLUP method with marker weights is faster, more accurate and easier to
      implement for GWAS applications without computing pseudo-data.

PMID- 22624568
TI  - Bayesian B-spline mapping for dynamic quantitative traits.
AB  - Owing to their ability and flexibility to describe individual gene expression at
      different time points, random regression (RR) analyses have become a popular
      procedure for the genetic analysis of dynamic traits whose phenotypes are
      collected over time. Specifically, when modelling the dynamic patterns of gene
      expressions in the RR framework, B-splines have been proved successful as an
      alternative to orthogonal polynomials. In the so-called Bayesian B-spline
      quantitative trait locus (QTL) mapping, B-splines are used to characterize the
      patterns of QTL effects and individual-specific time-dependent environmental
      errors over time, and the Bayesian shrinkage estimation method is employed to
      estimate model parameters. Extensive simulations demonstrate that (1) in terms of
      statistical power, Bayesian B-spline mapping outperforms the interval mapping
      based on the maximum likelihood; (2) for the simulated dataset with complicated
      growth curve simulated by B-splines, Legendre polynomial-based Bayesian mapping
      is not capable of identifying the designed QTLs accurately, even when higher
      order Legendre polynomials are considered and (3) for the simulated dataset using
      Legendre polynomials, the Bayesian B-spline mapping can find the same QTLs as
      those identified by Legendre polynomial analysis. All simulation results support
      the necessity and flexibility of B-spline in Bayesian mapping of dynamic traits.
      The proposed method is also applied to a real dataset, where QTLs controlling the
      growth trajectory of stem diameters in Populus are located.

PMID- 22624569
TI  - Different patterns of Robertsonian fusion pairing in Bovidae and the house mouse:
      the relationship between chromosome size and nuclear territories.
AB  - Using a dataset of karyotypic changes reported for bovids and the house mouse
      (Mus musculus domesticus) together with information from the cattle (Bos taurus)
      and mouse genomes, we examined two principal variables that have been proposed to
      predict chromosomal positioning in the nucleus, chromosome size and GC content.
      These were expected to influence the distribution of Robertsonian (Rb) fusions,
      the predominant mode of chromosomal change in both taxa. We found the largest
      chromosomes to be most frequently involved in fusions in bovids, and confirm
      earlier reports that chromosomes of intermediate size were the most frequent
      fusers in mice. We then tested whether chromosomal positioning can explain Rb
      fusion frequencies. We classified chromosomes into groups by size and considered
      the frequency of interactions between specific groups. Among the interactions,
      mouse chromosomes showed a slight tendency to fuse with neighbouring chromosomes,
      in line with expectations of chromosomal positioning, but also resembling
      predictions from meiotic spindle-induced bias. Bovids, on the other hand, showed
      no trend in interactions, with small chromosomes being the least frequent partner
      for all size classes. We discuss the results in terms of nuclear organization at
      various cell cycle stages and the proposed mechanisms of Rb fusion formation, and
      note that the difference can be explained by (i) considering bovid species
      generally to be characterized by a greater intermingling of chromosomal size
      classes than the house mouse, or (ii) by the vastly different timescales
      underpinning their evolutionary histories.

PMID- 22624570
TI  - Experiences from nutritional rehabilitation among under 5 children from a remote
      mountain area of Nepal.

PMID- 22624574
TI  - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics.

PMID- 22624571
TI  - Erratum.

PMID- 22624576
TI  - Nanoreactors by programmed enzyme encapsulation inside the capsid of the
      bacteriophage P22.
AB  - The virus like particle (VLP) derived from bacteriophage P22 presents a unique
      platform for constructing catalytically functional nanomaterials by encapsulation
      of enzymes into its interior. Encapsulation has been engineered to be genetically
      programmed allowing "one pot" synthesis and incorporation of desired enzymes. The
      unique characteristic that separates P22 from other VLP systems is the ability to
      modulate the overall volume and porosity of the VLP structure, thus controlling
      substrate access to the encapsulated enzyme. The present study demonstrates
      incorporation of an enzyme, alcohol dehydrogenase D, with the highest internal
      loading for an active enzyme by any VLP described thus far. In addition, we show
      that not only does encapsulating AdhD inside P22 affect its kinetic parameters in
      comparison with the "free" enzyme, but transformation of P22 to different
      morphological states, which changes the internal volume of the VLP, yields
      changes in the overall activity of the encapsulated enzyme as well. The findings
      reported here clearly illustrate that P22 holds potential for synthetic
      approaches to create nanoreactors, by design, using the power of highly evolved
      enzymes for chemical transformations.

PMID- 22624577
TI  - Infrared spectroscopic and theoretical investigations of the OUF2 and OThF2
      molecules with triple oxo bond character.
AB  - The terminal oxo species OUF(2) and OThF(2) have been prepared via the
      spontaneous and specific OF(2) molecule reactions with laser ablated uranium and
      thorium atoms in solid argon and neon. These isolated molecules are characterized
      by one terminal M-O and two F-M-F (M = U or Th) stretching vibrational modes
      observed in matrix isolation infrared spectra, which are further supported by
      density functional frequency calculations and CASPT2 energy and structure
      calculations. Both molecules have pyramidal structures with singlet (Th) and
      triplet (U) ground states. The molecular orbitals and metal-oxygen bond lengths
      for the OUF(2) and OThF(2) molecules indicate triple bond character for the
      terminal oxo groups, which are also substantiated by NBO analysis at the B3LYP
      level and by CASPT2 molecular orbital calculations. Dative bonding involving
      O(2p) -> Th(6d) and U(df) interactions is clearly involved in these oxoactinide
      difluoride molecules. Finally, the weak O-F bond in OF(2) as well as the strong U
      O, U-F and Th-O, Th-F bonds make reaction to form the OUF(2) and OThF(2)
      molecules highly exothermic.

PMID- 22624578
TI  - Imaging amyloid plaque in Alzheimer's disease brain with a biotinylated Abeta
      peptide radiopharmaceutical conjugated to an IgG-avidin fusion protein.
AB  - The Abeta amyloid peptide of Alzheimer's disease (AD) is a potentially large
      molecule radiopharmaceutical for imaging the brain amyloid burden, should the
      peptide be made transportable across the blood-brain barrier (BBB). Peptides can
      be made BBB-penetrating with the combined use of Trojan horse and avidin-biotin
      technologies. The peptide is monobiotinylated and attached to a fusion protein of
      avidin (AV) and a genetically engineered monoclonal antibody (mAb) against the
      human insulin receptor (HIR). The fusion protein is designated HIRMAb-AV, and is
      produced by stably transfected mammalian host cells grown in biotin free medium.
      The HIRMAb domain of the fusion protein acts as a molecular Trojan horse, which
      crosses the BBB via transport on the endogenous insulin receptor. The avidin
      domain of the fusion protein creates a high-affinity linker between the HIRMAb
      and the biotinylated peptide radiopharmaceutical. The 4 kDa Abeta(1-40) amyloid
      peptide of AD was N-biotinylated and radiolabeled with (125)I. The amyloid plaque
      binding of the [(125)I]-N-biotinyl-Abeta(1-40) peptide, either without or with
      conjugation to the HIRMAb-AV fusion protein, was tested with film autoradiography
      and tissue sections of autopsy AD brain. The study shows the biotinyl-Abeta(1-40)
      peptide still binds to amyloid plaque in AD brain to the same extent when the
      peptide radiopharmaceutical is either free or conjugated to the HIRMAb-AV fusion
      protein. The study supports further evaluation of antibody-targeted peptide
      radiopharmaceuticals as large molecule neuro-imaging agents that penetrate the
      BBB. 

PMID- 22624579
TI  - Prevalence and causes of monocular childhood blindness in a rural population in
      southern India.
AB  - PURPOSE: To determine the prevalence and etiology of childhood monocular
      blindness in a rural population in southern India. METHODS: A total of 14,423
      children younger than 15 years in randomly selected villages (8,222 households)
      with a total population of 40,336 were screened. Screening was performed in two
      stages. In the first stage, all children with visual acuity worse than 6/18 in at
      least one eye were screened. Subsequently, children with visual acuity worse than
      3/60 in one eye were referred to a tertiary care hospital for further examination
      for determination of the cause of visual impairment. RESULTS: The age range of
      affected children was 1 to 15 years (median age: 12 years). Fifteen children had
      monocular visual impairment, yielding a prevalence rate of 1.13 in 1,000
      children. Refractive error leading to amblyopia was the most common cause of
      monocular visual impairment, followed by trauma, congenital disorders, and
      vitamin A deficiency. One case had toxoplasmosis. Approximately one-third of the
      children were born of a consanguineous marriage (30.06%). The proportion of first
      degree consanguinity (46.4%) was higher than that of second-degree (37.5%) or
      third-degree (16.1%) consanguinity. CONCLUSION: The prevalence of childhood
      monocular blindness was high in the current study, but most causes were
      preventable or treatable. Improved screening methods (especially for refractive
      errors), genetic counseling, and therapeutic interventions can reduce the burden
      of childhood blindness.

PMID- 22624580
TI  - Comparative cross-sectional study of empathy among first year and final year
      medical students in Jimma University, Ethiopia: steady state of the heart and
      opening of the eyes.
AB  - BACKGROUND: There is general consent that empathy is crucial for the physician
      patient relationship and thus an important issue in medical education. This
      comparative study was designed to examine the differences in empathy between
      first year and final year medical students in Jimma University, Ethiopia.
      METHODS: A comparative cross-sectional study among 131 first year and 106 final
      year medical students was conducted in Jimma University, Ethiopia on academic
      year 2010/11. The study subjects were selected using simple random sampling
      technique from the list of the students. Study participation was voluntary. The
      Balanced Emotional Empathy Scale (BEES) was used for the detection of "heart
      reading", i.e. emotional empathy and the Reading the Mind in the Eyes test (RME-R
      test) to evaluate "mind-reading", i.e. cognitive empathy. We performed t-test to
      compare the mean difference in empathy and RME-R scores between the two groups of
      students. A linear regression was computed to identify potential factors
      influencing the BEES and RME-R. RESULTS: Out of the total 237 students, 207
      (87.3%) were males. The mean age of first year and final year students was 19.3
      +/- 1.1 and 24.0 +/- 1.4 years respectively. First year students have scored 40.6
      +/- 23.8 while final year students scored 41.5 +/- 20.8 mean in the BEES
      measuring emotional empathy score. However, this difference was not statistically
      significant (t = -0.30, df = 231, P-value >0.05). Final year students had
      significantly higher mean cognitive empathy score (17.8 +/- 4.5) than first year
      students (14.4 +/- 4.8) [beta = 2.7, 95%CI (1.20, 4.13)]. Males had scored lower
      cognitive [beta = -2.5, 95%CI (-4.37, -0.66)] and emotional empathy [beta = 
      12.0, 95%CI (-21.66, -5.46)]. CONCLUSIONS: Low emotional (BEES) and cognitive
      empathy sores were found in first year and final year students of Jimma
      University could have implications on the medical education curricula. Medical
      education targeted at enhancing emotional empathy and increasing cognitive
      empathy is required by segmenting with gender for effective physician-patient
      interaction. The influence of empathy on clinical competence should be studied
      using more rigorous design.

PMID- 22624582
TI  - Coagulation and fibrinolysis abnormalities in familial amyloid polyneuropathy.
AB  - OBJECTIVE: Familial amyloid polyneuropathy (FAP) is an autosomal dominant form of
      hereditary amyloidosis. Several studies reported coagulation factor X deficiency
      and excessive fibrinolysis in immunoglobulin light chain amyloidosis. However,
      few have investigated coagulation and fibrinolysis in FAP. The objective of this
      study was to determine abnormalities in plasma biomarkers of coagulation and
      fibrinolysis in FAP. METHODS: We prospectively recruited eight FAP patients with
      transthyretin mutations and ten age-matched control patients with other
      neuropathies in our university. We examined plasma biomarkers of coagulation and
      fibrinolysis including prothrombin time, activated partial thromboplastin time,
      fibrinogen, fibrin/fibrinogen degradation products, D-dimer, alpha2-antiplasmin,
      antithrombin, plasminogen, thrombin-antithrombin complex, plasmin-alpha2
      antiplasmin complex, prothrombin fragment 1+2, and coagulation factor X. The Mann
      Whitney U test was performed for statistical comparisons between FAP and control
      groups. RESULTS: FAP patients exhibited significantly decreased levels of
      coagulation factor X, plasminogen and alpha2-antiplasmin, and significantly
      increased levels of prothrombin fragment 1+2 compared to control patients.
      CONCLUSION: Our results indicate abnormalities of coagulation and fibrinolysis in
      FAP patients.

PMID- 22624581
TI  - Anti-herpes virus activities of bioactive fraction and isolated pure constituent
      of Mallotus peltatus: an ethnomedicine from Andaman Islands.
AB  - BACKGROUND: Viral infections, particularly the infections caused by herpes
      simplex virus (HSV), represent one of the most serious public health concerns
      globally because of their devastating impact. The aim of this study was to
      evaluate the antiviral potential of methanolic crude extract of an ethnomedicine
      Mallotus peltatus, its active fraction and pure compound, against HSV-1 F and HSV
      2 G. RESULT: The cytotoxicity (CC(50), the concentration of 50% cellular
      toxicity), antiviral effective concentration (EC(50), the concentration required
      to achieve 50% protection against virus-induced cytopathic effect), plaque
      reduction and the selectivity index (SI, the ratio of CC(50) and EC(50)) was
      determined. Results showed that the crude methanolic extract of M. peltatus
      possessed weak anti-HSV activity. In contrast, the active fraction A and isolated
      ursolic acid from fraction A exhibited potent antiherpesvirus activity against
      both HSV-1 (EC(50)= 7.8 and 5.5 MUg/ml; SI = 22.3 and 20) and HSV-2 (EC(50)= 8.2
      and 5.8 MUg/ml, and SI = 21.2 and 18.97). The fraction A and isolated ursolic
      acid (10 MUg/ml) inhibited plaque formation of HSV-1 and HSV-2 at more than 80%
      levels, with a dose dependent antiviral activity, compared to acyclovir. The time
      response study revealed that the anti-HSV activity of fraction A and isolated
      ursolic acid is highest at 2-5 h post-infection. Moreover, the time kinetics
      study by indirect immunofluorescence assay showed a characteristic pattern of
      small foci of single fluorescent cells in fraction A- treated virus infected
      cells at 2 h and 4 h post-infection, suggesting drug inhibited viral
      dissemination. Further, the PCR study with infected cell cultures treated with
      fraction A and isolated ursolic acid at various time intervals, failed to show
      amplification at 48-72 h, like acyclovir treated HSV-infected cells. Moreover,
      fraction A or isolated ursolic acid showed no interaction in combination with
      acyclovir. CONCLUSION: This study revealed that bioactive fraction A and isolated
      ursolic acid of M. peltatus has good anti-HSV activity, probably by inhibiting
      the early stage of multiplication (post-infection of 0-5 h), with SI value of 20,
      suggesting its potential use as anti-HSV agents.

PMID- 22624583
TI  - Thermodynamic impact of embedded water molecules in the unfolding of human CD2BP2
      GYF domain.
AB  - GYF domains are small polyproline-recognition modules adopting a structural
      arrangement consisting of a single alpha-helix packed against a small beta-sheet.
      Although most families of proline-rich recognition modules have been extensively
      characterized in terms of function, structure, or conformational flexibility,
      little is known about GYF domain functionality and folding. We have undertaken
      the thermodynamic characterization of the unfolding of CD2BP2-GYF domain by
      combining differential scanning calorimetry and circular dichroism under
      different pH conditions. The experimental data can be well-described in terms of
      a two-state equilibrium, although an unusually high heat capacity of the native
      state reflects a considerable conformational flexibility and dynamics of CD2BP2
      GYF domain. In addition, the normalized thermodynamic parameters of unfolding
      (enthalpy, entropy and heat capacity) are roughly a factor of two greater than
      expected. In contrast, stability curves reveal an ordinary unfolding behavior of
      CD2BP2-GYF domain in terms of Gibbs energies, incurring thus unusually strong
      enthalpy-entropy compensation. This phenomenon, previously described as
      "thermodynamic homeostasis", has been associated in different examples to the
      contribution of occluded water (solvent) molecules into the protein structure. By
      means of CASTp server, we have found seven cavities/pockets scattered throughout
      of the CD2BP2-GYF structure, each able to harbor at least one water molecule.
      This structural feature provides rationalization for the atypical enthalpy values
      observed for CD2BP2-GYF because each water molecule is able to organize an extra
      amount of hydrogen bonds in the native state. In addition, these bound waters
      increase the vibrational entropy of the protein, which could also be responsible
      for an increase in protein flexibility and may thus fully explain the homeostatic
      behavior experimentally observed.

PMID- 22624584
TI  - Copper(II)-mediated layer-by-layer assembly of viologenthiol-functionalized
      carbon nanotube hybrid multilayers: preparation, characterization, morphology,
      and electrochemical properties.
AB  - The metal-mediated self-assembly of coordination polymers, building blocks, and
      metal-organic frameworks has been widely used to construct multifunctional novel
      materials on the molecular level. Here, we developed this technique to build up
      multilayers of functionalized carbon nanotubes on the basis of both
      intermolecular electrostatic and coordinative interactions. Positively charged
      electroactive viologenthiol (VSH) was first immobilized on multiwalled carbon
      nanotubes (MWNTs) to form MWNT-VSH hybrids with a relative content of ~9% by
      weight. Field emission transmission electron microscopy images revealed that the
      VSH molecules randomly covered the surfaces of MWNTs with a thickness of 1 to 2
      nm. Then, the MWNT-VSH hybrids were used as nanoscale multidentate "ligands"
      (linkers) to construct metal-mediated multilayers with the use of CuAc(2) as the
      connectors by the layer-by-layer (LBL) method. The assembly process was monitored
      by absorption and X-ray photoelectron spectroscopy as well as scanning electron
      and atomic force microscopy after each assembly of Cu(II) ions and MWNT-VSH
      hybrids. Finally, the electrochemical behaviors of the viologens in the MWNT
      VS/Cu LBL multilayers were investigated.

PMID- 22624585
TI  - Blood transfusions increase circulating plasma free hemoglobin levels and plasma
      nitric oxide consumption: a prospective observational pilot study.
AB  - INTRODUCTION: The increasing number of reports on the relation between
      transfusion of stored red blood cells (RBCs) and adverse patient outcome has
      sparked an intense debate on the benefits and risks of blood transfusions.
      Meanwhile, the pathophysiological mechanisms underlying this postulated relation
      remain unclear. The development of hemolysis during storage might contribute to
      this mechanism by release of free hemoglobin (fHb), a potent nitric oxide (NO)
      scavenger, which may impair vasodilation and microcirculatory perfusion after
      transfusion. The objective of this prospective observational pilot study was to
      establish whether RBC transfusion results in increased circulating fHb levels and
      plasma NO consumption. In addition, the relation between increased fHb values and
      circulating haptoglobin, its natural scavenger, was studied. METHODS: Thirty
      patients electively received 1 stored packed RBC unit (n = 8) or 2 stored packed
      RBC units (n = 22). Blood samples were drawn to analyze plasma levels of fHb,
      haptoglobin, and NO consumption prior to transfusion, and 15, 30, 60 and 120
      minutes and 24 hours after transfusion. Differences were compared using Pearson's
      chi-square test or Fisher's exact test for dichotomous variables, or an
      independent-sample t test or Mann-Whitney U test for continuous data. Continuous,
      multiple-timepoint data were analyzed using repeated one-way analysis of variance
      or the Kruskall-Wallis test. Correlations were analyzed using Spearman or Pearson
      correlation. RESULTS: Storage duration correlated significantly with fHb
      concentrations and NO consumption within the storage medium (r = 0.51, P < 0.001
      and r = 0.62, P = 0.002). fHb also significantly correlated with NO consumption
      directly (r = 0.61, P = 0.002). Transfusion of 2 RBC units significantly
      increased circulating fHb and NO consumption in the recipient (P < 0.001 and P <
      0.05, respectively), in contrast to transfusion of 1 stored RBC unit. Storage
      duration of the blood products did not correlate with changes in fHb and NO
      consumption in the recipient. In contrast, pre-transfusion recipient plasma
      haptoglobin levels inversely influenced post-transfusion fHb concentrations.
      CONCLUSION: These data suggest that RBC transfusion can significantly increase
      post-transfusion plasma fHb levels and plasma NO consumption in the recipient.
      This finding may contribute to the potential pathophysiological mechanism
      underlying the much-discussed adverse relation between blood transfusions and
      patient outcome. This observation may be of particular importance for patients
      with substantial transfusion requirements.

PMID- 22624586
TI  - Case of complete response to everolimus for metastatic renal cell carcinoma.

PMID- 22624587
TI  - Central thalamic deep brain stimulation to promote recovery from chronic
      posttraumatic minimally conscious state: challenges and opportunities.
AB  - BACKGROUND: Central thalamic deep brain stimulation (CT-DBS) may have therapeutic
      potential to improve behavioral functioning in patients with severe traumatic
      brain injury (TBI), but its use remains experimental. Current research suggests
      that the central thalamus plays a critical role in modulating arousal during
      tasks requiring sustained attention, working memory, and motor function. The aim
      of the current article is to review the methodology used in the CT-DBS protocol
      developed by our group, outline the challenges we encountered and offer
      suggestions for future DBS trials in this population. RATIONAL FOR CT-DBS IN TBI:
      CT-DBS may therefore be able to stimulate these functions by eliciting action
      potentials that excite thalamocortical and thalamostriatal pathways. Because
      patients in chronic minimally conscious state (MCS) have a very low probability
      of regaining functional independence, yet often have significant sparing of
      cortical connectivity, they may represent a particularly appropriate target group
      for CT-DBS. PIlOT STUDY RESULTS:  We have conducted a series of single-subject
      studies of CT-DBS in patients with chronic posttraumatic MCS, with 24-month
      follow-up. Outcomes were measured using the Coma Recovery Scale-Revised as well
      as a battery of secondary outcome measures to capture more granular changes.
      Findings from our index case suggest that CT-DBS can significantly increase
      functional communication, motor performance, feeding, and object naming in the
      DBS on state, with performance in some domains remaining above baseline even
      after DBS was turned off. CONCLUSIONS: The use of CT-DBS in patients in MCS,
      however, presents challenges at almost every step, including during surgical
      planning, outcome measurement, and postoperative care. Additionally, given the
      difficulties of obtaining informed consent from patients in MCS and the
      experimental nature of the treatment, a robust, scientifically rooted ethical
      framework is resented for pursuing this line of work.

PMID- 22624593
TI  - {4-t-Bu-2,6-[P(O)(O-i-Pr)2]2C6H2Sn}2: an intramolecularly coordinated
      organotin(I) compound with a Sn-Sn single bond, its disproportionation toward a
      diorganostannylene and elemental tin, and its oxidation with PhI(OAc)2.
AB  - Syntheses of the intramolecularly coordinated organotin(I) compound {4-t-Bu-2,6
      [P(O)(O-i-Pr)(2)](2)C(6)H(2)Sn}(2) (2), which crystallized in two different
      pseudopolymorphs 2 and 2.C(7)H(8), of the diorganostannylene {4-t-Bu-2,6-[P(O)(O
      i-Pr)(2)](2)C(6)H(2)}(2)Sn (3) and of the organotin(II) acetate 4-t-Bu-2,6
      [P(O)(O-i-Pr)(2)](2)C(6)H(2)SnOAc (4) are reported. The compounds were
      characterized by multinuclear NMR, IR (3 and 4), UV-vis spectroscopy (2),
      electrospray ionization mass spectrometry (3 and 4), and single-crystal X-ray
      diffraction analyses. Density functional theory calculations on compound 2
      revealed the stabilizing effect of the intramolecular P?O -> Sn coordination.

PMID- 22624592
TI  - Capsid coding sequences of foot-and-mouth disease viruses are determinants of
      pathogenicity in pigs.
AB  - The surface exposed capsid proteins, VP1, VP2 and VP3, of foot-and-mouth disease
      virus (FMDV) determine its antigenicity and the ability of the virus to interact
      with host-cell receptors. Hence, modification of these structural proteins may
      alter the properties of the virus.In the present study we compared the
      pathogenicity of different FMDVs in young pigs. In total 32 pigs, 7-weeks-old,
      were exposed to virus, either by direct inoculation or through contact with
      inoculated pigs, using cell culture adapted (O1K B64), chimeric (O1K/A-TUR and
      O1K/O-UKG) or field strain (O-UKG/34/2001) viruses. The O1K B64 virus and the two
      chimeric viruses are identical to each other except for the capsid coding
      region.Animals exposed to O1K B64 did not exhibit signs of disease, while pigs
      exposed to each of the other viruses showed typical clinical signs of foot-and
      mouth disease (FMD). All pigs infected with the O1K/O-UKG chimera or the field
      strain (O-UKG/34/2001) developed fulminant disease. Furthermore, 3 of 4 in
      contact pigs exposed to the O1K/O-UKG virus died in the acute phase of infection,
      likely from myocardial infection. However, in the group exposed to the O1K/A-TUR
      chimeric virus, only 1 pig showed symptoms of disease within the time frame of
      the experiment (10 days). All pigs that developed clinical disease showed a high
      level of viral RNA in serum and infected pigs that survived the acute phase of
      infection developed a serotype specific antibody response. It is concluded that
      the capsid coding sequences are determinants of FMDV pathogenicity in pigs.

PMID- 22624591
TI  - Relationship between total bilirubin and endothelial function, inflammation and
      oxidative stress in HIV-infected adults on stable antiretroviral therapy.
AB  - OBJECTIVES: Enhanced inflammation is evident in HIV infection, even with
      virological suppression. Outside HIV infection, studies show an independent
      association between higher total bilirubin and better endothelial function as
      well as a lower prevalence of coronary heart disease, possibly as a consequence
      of the anti-inflammatory and antioxidant effect of bilirubin. The aim of this
      study was to determine whether such an association exists in HIV-infected
      individuals. METHODS: A cross-sectional study was performed in HIV-1-infected
      adults on stable antiretroviral therapy (ART) to determine if a relationship
      exists between total bilirubin and endothelial function [flow-mediated dilation
      (FMD) of the brachial artery], inflammation [interleukin-6 (IL-6), soluble tumour
      necrosis factor receptors, C-reactive protein, and adhesion molecules],
      coagulation markers (fibrinogen and D-dimer) and oxidative stress (F (2) 
      isoprostanes). Endpoints were compared based on total bilirubin levels and
      atazanavir status using distributionally appropriate, two-sample tests.
      Correlation coefficients were determined between total bilirubin and endpoints.
      Linear regression was used to model the relationship between total bilirubin (and
      atazanavir status) and FMD. RESULTS: A total of 98 adults were included in the
      study. Total bilirubin was higher in the atazanavir group when compared to the
      non-atazanavir group [median (interquartile range) 1.8 (1.1-2.6) vs. 0.6 (0.4
      1.4) mg/dL; P < 0.01] as were insulin, the homeostasis model assessment of
      insulin resistance (HOMA-IR) and fibrinogen. Total bilirubin was positively
      correlated with fibrinogen and was not correlated with other outcomes. After
      adjustment, neither total bilirubin nor atazanavir status was associated with
      FMD. CONCLUSIONS: In virologically suppressed, HIV-infected adults on stable ART,
      neither total bilirubin nor atazanavir use was associated with improved
      endothelial function as measured using FMD, inflammation or oxidative stress as
      measured using biomarkers.

PMID- 22624594
TI  - A prospective clinical trial evaluating the safety and efficacy of the
      combination of rituximab and plerixafor as a mobilization regimen for patients
      with lymphoma.
AB  - BACKGROUND: Previous reports suggested that rituximab may impair stem cell
      collection and posttransplant engraftment in lymphoma patients undergoing
      autologous hematopoietic progenitor cell transplantation. STUDY DESIGN AND
      METHODS: A prospective biologic allocation study examined the effect of adding
      rituximab to a mobilization regimen of plerixafor and granulocyte-colony
      stimulating factor (G-CSF) for patients with CD20+ lymphoma compared with CD20-
      lymphoma patients mobilized without rituximab. The primary endpoint was safety of
      the rituximab-containing regimen; secondary endpoints compared the efficiency of
      stem cell collection, posttransplant engraftment, graft characteristics,
      mobilization kinetics, immune reconstitution, and engraftment durability between
      the cohorts of patients with CD20+ and CD20- lymphoma. RESULTS: Fifteen subjects
      assigned to each treatment arm were accrued. Both mobilization regimens had
      similar toxicities. The median number of CD34+ cells collected (7.4 * 10(6) /kg
      vs. 6.4 * 10(6) /kg) and the median numbers of days of apheresis needed to
      collect stem cells were not different between the CD20+ and CD20- cohorts. No
      significant differences in neutrophil engraftment (median, 13.5 days vs. 13 days)
      or platelet engraftment (22 vs. 21 days) or in graft durability were seen
      comparing patients with CD20+ versus CD20- lymphoma. There were no significant
      differences in the kinetics of blood T-cell or natural killer-cell reconstitution
      comparing the two groups. B-cell reconstitution was delayed in the CD20+ lymphoma
      group, but this did not translate into a significant increase in infectious
      complications. CONCLUSION: Rituximab can be safely added to the combination of
      plerixafor and G-CSF as a mobilization strategy without excess toxicity or
      posttransplant engraftment delays for patients with chemosensitive lymphoma
      undergoing autologous hematopoietic progenitor cell transplantation.

PMID- 22624595
TI  - Incorporating geographical and evolutionary rarity into conservation
      prioritization.
AB  - Key goals of conservation are to protect both species and the functional and
      genetic diversity they represent. A strictly species-based approach may
      underrepresent rare, threatened, or genetically distinct species and
      overrepresent widespread species. Although reserves are created for a number of
      reasons, including economic, cultural, and ecological reasons, their efficacy has
      been measured primarily in terms of how well species richness is protected, and
      it is useful to compare how well they protect other measures of diversity. We
      used Proteaceae species-occurrence data in the Cape Floristic Region of South
      Africa to illustrate differences in the spatial distribution of species and
      evolutionary diversity estimated from a new maximum-likelihood molecular
      phylogeny. We calculated species richness, phylogenetic diversity (i.e., summed
      phylogenetic branch lengths in a site), and a site-aggregated measure of
      biogeographically weighted evolutionary distinctiveness (i.e., an abundance
      weighted measure that captures the unique proportion of the phylogenetic tree a
      species represents) for sites throughout the Cape Floristic Region. Species
      richness and phylogenetic diversity values were highly correlated for sites in
      the region, but species richness was concentrated at a few sites that
      underrepresented the much more spatially extensive distribution of phylogenetic
      diversity. Biogeographically weighted evolutionary diversity produced a scheme of
      prioritization distinct from the other 2 metrics and highlighted southern sites
      as conservation priorities. In these sites, the high values of biogeographically
      weighted evolutionary distinctiveness were the result of a nonrandom relation
      between evolutionary distinctiveness and geographical rarity, where rare species
      also tended to have high levels of evolutionary distinctiveness. Such distinct
      and rare species are of particular concern, but are not captured by conservation
      schemes that focus on species richness or phylogenetic diversity alone.

PMID- 22624596
TI  - Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura
      and other thrombotic microangiopathies.

PMID- 22624597
TI  - One and done? Equality of opportunity and repeated access to scarce, indivisible
      medical resources.
AB  - BACKGROUND: Existing ethical guidelines recommend that, all else equal, past
      receipt of a medical resource (e.g. a scarce organ) should not be considered in
      current allocation decisions (e.g. a repeat transplantation). DISCUSSION: One
      stated reason for this ethical consensus is that formal theories of ethics and
      justice do not persuasively accept or reject repeated access to the same medical
      resources. Another is that restricting attention to past receipt of a particular
      medical resource seems arbitrary: why couldn't one just as well, it is argued,
      consider receipt of other goods such as income or education? In consequence,
      simple allocation by lottery or first-come-first-served without consideration of
      any past receipt is thought to best afford equal opportunity, conditional on
      equal medical need.There are three issues with this view that need to be
      addressed. First, public views and patient preferences are less ambiguous than
      formal theories of ethics. Empirical work shows strong preferences for fairness
      in health care that have not been taken into account: repeated access to
      resources has been perceived as unfair. Second, while difficult to consider
      receipt of many other prior resources including non-medical resources, this
      should not be used a motive for ignoring the receipt of any and all goods
      including the focal resource in question. Third, when all claimants to a scarce
      resource are equally deserving, then use of random allocation seems warranted.
      However, the converse is not true: mere use of a randomizer does not by itself
      make the merits of all claimants equal. SUMMARY: My conclusion is that not
      ignoring prior receipt of the same medical resource, and prioritizing those who
      have not previously had access to the medical resource in question, may be
      perceived as fairer and more equitable by society.

PMID- 22624598
TI  - Using 3-6 differences in essential fatty acids rather than 3/6 ratios gives
      useful food balance scores.
AB  - BACKGROUND: The vitamin-like omega-3 and omega-6 essential fatty acids are
      converted in the body to a large family of hormones which act at selective
      receptors that occur on nearly every cell and tissue. A relative omega-3 deficit
      allows overabundant actions of omega-6 hormones to develop into health disorders.
      People need simple, explicit information on the balance of essential fatty acids
      in their foods to avoid accumulating unintended imbalances in their tissue omega
      3 and omega-6 fatty acids. RESULTS: We developed an Omega 3-6 Balance Food Score
      that summarizes in a single value the balance among eleven omega-3 and omega-6
      essential fatty acids in a food. The value allows a quantitative estimate of the
      impact of each food item on the proportions of omega-3 and omega-6 that will
      accumulate in the 20- and 22-carbon highly unsaturated fatty acids of blood,
      which is an important health risk assessment biomarker. CONCLUSIONS: The impact
      of an individual food item upon a useful health risk assessment biomarker is
      easily evident in a simple, explicit value for the balance among eleven essential
      fatty acids nutrients. Foods with more positive Omega 3-6 Balance Food Scores
      will increase the percent of omega-3 in the biomarker, whereas those with more
      negative Scores will increase the percent of omega-6 in the biomarker.

PMID- 22624599
TI  - Analytical methods for characterizing magnetic resonance probes.
AB  - The efficiency of Gd(III) contrast agents in magnetic resonance image enhancement
      is governed by a set of tunable structural parameters. Understanding and
      measuring these parameters requires specific analytical techniques. This Feature
      describes strategies to optimize each of the critical Gd(III) relaxation
      parameters for molecular imaging applications and the methods employed for their
      evaluation.

PMID- 22624600
TI  - Timing of electron and proton transfer in the ba(3) cytochrome c oxidase from
      Thermus thermophilus.
AB  - Heme-copper oxidases are membrane-bound proteins that catalyze the reduction of
      O(2) to H(2)O, a highly exergonic reaction. Part of the free energy of this
      reaction is used for pumping of protons across the membrane. The ba(3) oxidase
      from Thermus thermophilus presumably uses a single proton pathway for the
      transfer of substrate protons used during O(2) reduction as well as for the
      transfer of the protons that are pumped across the membrane. The pumping
      stoichiometry (0.5 H(+)/electron) is lower than that of most other (mitochondrial
      like) oxidases characterized to date (1 H(+)/electron). We studied the pH
      dependence and deuterium isotope effect of the kinetics of electron and proton
      transfer reactions in the ba(3) oxidase. The results from these studies suggest
      that the movement of protons to the catalytic site and movement to a site located
      some distance from the catalytic site [proposed to be a "proton-loading site"
      (PLS) for pumped protons] are separated in time, which allows individual
      investigation of these reactions. A scenario in which the uptake and release of a
      pumped proton occurs upon every second transfer of an electron to the catalytic
      site would explain the decreased proton pumping stoichiometry compared to that of
      mitochondrial-like oxidases.

PMID- 22624601
TI  - Dual-responsive controlled drug delivery based on ionically assembled
      nanoparticles.
AB  - Ionically assembled nanoparticles (INPs) have been formed from poly(ionic liquid
      co-N-isopropylacrylamide) with deoxycholic acid through electrostatic
      interaction. The structure and properties of the INPs were investigated by using
      (1)H NMR, Fourier transform infrared (FTIR), transmission electron microscopy
      (TEM), dynamic light scattering (DLS), and so on. Due to pH-responsive
      deoxycholic acid (pK(a) = 6.2) and thermo responsive N-isopropylacrylamide
      included in the ionic complex, the INPs exhibit highly pH and thermal dual
      responsive properties. The potential practical applications as drug delivery
      carriers were demonstrated using doxorubicin (DOX) as a model drug. With a lower
      pH (pH 5.2) and higher temperature (above 37  degrees C), structural collapse of
      the INPs occurred as well as release of DOX owing to protonated DA departure from
      the INPs and a lower LCST (lower critical solution temperature) at the
      pathological conditions. The result shows that 80% of DOX molecules were released
      from INPs within 48 h at pH 5.2, 43  degrees C, but only 30% of the drug was
      released within 48 h at 37  degrees C and pH 7.4. Moreover, drug-loaded INPs
      exhibit an inhibitory effect on cell growth.

PMID- 22624602
TI  - Intramolecular aryl-aryl coupling of fluoroarenes through Al2O3-mediated HF
      elimination.
AB  - A strategy for effective intramolecular aryl-aryl coupling of fluoroarenes
      through Al(2)O(3)-mediated HF elimination is reported. It is demonstrated that
      the C-F bond, which is widely believed to be the most passive functionality in
      organic chemistry, can be reconsidered as a useful functional group allowing very
      effective C-C bond formation. The solid-state strategy presented in this study
      opens the possibility for facile syntheses of insoluble extended polycyclic
      aromatic hydrocarbons.

PMID- 22624603
TI  - Serum amyloid A and cholesterol: a pivotal role on inflammation.

PMID- 22624604
TI  - Hericium erinaceus mushroom extracts protect infected mice against Salmonella
      Typhimurium-Induced liver damage and mortality by stimulation of innate immune
      cells.
AB  - The present study investigated the antibacterial effect of four extracts from the
      fruitbody of the edible medicinal mushroom  Hericium erinaceus  (hot water
      extract, HWE; microwave/50% ethanol extract, MWE; acid extract, ACE; and alkaline
      extract, AKE) against murine salmonellosis. The extracts had no effect on 
      Salmonella  ser. Typhimurium growth in culture. Nor were the extracts toxic to
      murine macrophage cells, RAW 264.7. HWE and MWE stimulated uptake of the bacteria
      into the macrophage cells as indicated by increased colony-forming unit (CFU)
      counts of the contents of the lysed macrophages infected with Salmonella
      Typhimurium for 30 and 60 min. Two hours postinfection, the bacterial counts
      increased in the macrophages, but 4 and 8 h postinfection the HWE- and MWE
      treated cells showed greater activity against the bacteria than the control. HWE-
      and MWE-treated noninfected macrophages had altered morphology and elevated
      inducible nitric oxide (NO) synthase (iNOS) mRNA expression. In the presence of
      S. Typhimurium, iNOS mRNA expression was further increased, accompanied by an
      increase in NO production. Histology assays of the livers of mice infected with a
      sublethal dose (1 * 10(4) CFU) of S. Typhimurium showed that HWE and MWE,
      administered by daily intraperitoneal injection, protected against necrosis of
      the liver, a biomarker of in vivo salmonellosis. The lifespans of mice similarly
      infected with a lethal dose of S. Typhimurium (1 * 10(5) CFU) were significantly
      extended by HWE and MWE. beta-Glucan, known to stimulate the immune system, was
      previously found to be present in high amounts in the active extracts. These
      results suggest that the mushroom extract activities against bacterial infection
      in mice occur through the activation of innate immune cells.

PMID- 22624605
TI  - When less is more: evidence for a facilitative cathodal tDCS effect in
      attentional abilities.
AB  - Many previous studies reported that the hyperpolarization of cortical neurons
      following cathodal stimulation (in transcranial direct current stimulation) has
      resulted in cognitive performance degradation. Here, we challenge this assumption
      by showing that cathodal stimulation will not always degrade cognitive
      performance. We used an attentional load paradigm in which irrelevant stimuli are
      processed only under low but not under high attentional load. Thirty healthy
      participants were randomly allocated into three interventional groups with
      different brain stimulation parameters (active anodal posterior parietal cortex
      [PPC], active cathodal PPC, and sham). Cathodal but not anodal stimulation
      enabled flanker processing even in high-loaded scenes. A second experiment was
      carried out to assert whether the improved flanker processing under cathodal
      stimulation is because of altered attention allocation between center and
      surround or, alternatively, enhanced attentional resources. In this experiment,
      the flanker was presented centrally. The results of Experiment 2 replicated
      Experiment 1's finding of improved flanker processing. We interpret the results
      from these two experiments as evidence for the ability of cathodal stimulation to
      enhance attentional resources rather than simply change attention allocation
      between center and periphery. Cathodal stimulation in high-loaded scenes can act
      like a noise filter and may in fact enhance cognitive performance. This study
      contributes to understanding the way the PPC is engaged with attentional
      functions and explains the cathodal effects, which thus might lead to more
      efficient brain stimulation protocols.

PMID- 22624606
TI  - Response suppression by automatic retrieval of stimulus-stop association:
      evidence from transcranial magnetic stimulation.
AB  - Behavioral studies show that subjects respond more slowly to stimuli to which
      they previously stopped. This response slowing could be explained by "automatic
      inhibition" (i.e., the reinstantiation of motor suppression when a stimulus
      retrieves a stop association). Here we tested this using TMS. In Experiment 1,
      participants were trained to go or no-go to stimuli. Then, in a test phase, we
      compared the corticospinal excitability for go stimuli that were previously
      associated with stopping (no-go_then_go) with go stimuli that were previously
      associated with going (go_then_go). Corticospinal excitability was reduced for no
      go_then_go compared with go_then_go stimuli at a mere 100 msec poststimulus.
      Although these results fit with automatic inhibition, there was, surprisingly, no
      suppression for no-go_then_no-go stimuli, although this should occur. We
      speculated that automatic inhibition lies within a continuum between effortful
      top-down response inhibition and no inhibition at all. When the need for
      executive control and active response suppression disappears, so does the
      manifestation of automatic inhibition. Therefore, it should emerge during go/no
      go learning and disappear as performance asymptotes. Consistent with this idea,
      in Experiment 2, we demonstrated reduced corticospinal excitability for no-go
      versus go trials most prominently in the midphase of training but it wears off as
      performance asymptotes. We thus provide neurophysiological evidence for an
      inhibition mechanism that is automatically reinstantiated when a stimulus
      retrieves a learned stopping episode, but only in an executive context in which
      active suppression is required. This demonstrates that automatic and top-down
      inhibition jointly contribute to goal-directed behavior.

PMID- 22624607
TI  - Task-relevant and task-irrelevant dimensions are modulated independently at a
      task-irrelevant location.
AB  - Single-cell and fMRI experiments indicate that task-relevant features are
      enhanced globally across the visual field (VF). Moreover, this global feature
      based attention can spread to task-irrelevant features of the attended object.
      Here we ask whether a task-irrelevant feature, by virtue of being bound to a task
      relevant feature, can also be enhanced at a task-irrelevant location.
      Specifically, we asked whether attending to the color of moving dots in one VF
      would influence the motion signal to colored moving dots in the other VF.
      Participants attended to either red or cyan dots, superimposed and moving in
      opposite directions. Critically, the color and motion of dots present in the
      opposite VF varied as a function of the attended dots such that they were either
      the same color/same direction, same color/opposite direction, opposite color/same
      direction, or opposite color/opposite direction as the attended dots. We found
      greater activity in ventral visual cortex when either the color or direction of
      motion matched the color or direction of motion at the attended location. Similar
      effects were found for direction of motion in human medial temporal/medial
      superior temporal cortex. Moreover, the color and motion effects did not interact
      in any region. Together, these results suggest that the coselection of an
      object's features modulates those features independently beyond the selected
      object.

PMID- 22624608
TI  - Multiple cognitive abilities from a single cortical algorithm.
AB  - One strong claim made by the representational-hierarchical account of cortical
      function in the ventral visual stream (VVS) is that the VVS is a functional
      continuum: the basic computations carried out in service of a given cognitive
      function, such as recognition memory or visual discrimination, might be the same
      at all points along the VVS. Here, we use a single-layer computational model with
      a fixed learning mechanism and set of parameters to simulate a variety of
      cognitive phenomena from different parts of the functional continuum of the VVS:
      recognition memory, categorization of perceptually related stimuli, perceptual
      learning of highly similar stimuli, and development of retinotopy and orientation
      selectivity. The simulation results indicate--consistent with the
      representational-hierarchical view--that the simple existence of different levels
      of representational complexity in different parts of the VVS is sufficient to
      drive the emergence of distinct regions that appear to be specialized for solving
      a particular task, when a common neurocomputational learning algorithm is assumed
      across all regions. Thus, our data suggest that it is not necessary to invoke
      computational differences to understand how different cortical regions can appear
      to be specialized for what are considered to be very different psychological
      functions.

PMID- 22624609
TI  - Mammalian tissues defective in nonsense-mediated mRNA decay display highly
      aberrant splicing patterns.
AB  - BACKGROUND: Nonsense-mediated mRNA decay (NMD) affects the outcome of alternative
      splicing by degrading mRNA isoforms with premature termination codons. Splicing
      regulators constitute important NMD targets; however, the extent to which loss of
      NMD causes extensive deregulation of alternative splicing has not previously been
      assayed in a global, unbiased manner. Here, we combine mouse genetics and RNA-seq
      to provide the first in vivo analysis of the global impact of NMD on splicing
      patterns in two primary mouse tissues ablated for the NMD factor UPF2. RESULTS:
      We developed a bioinformatic pipeline that maps RNA-seq data to a combinatorial
      exon database, predicts NMD-susceptibility for mRNA isoforms and calculates the
      distribution of major splice isoform classes. We present a catalog of NMD
      regulated alternative splicing events, showing that isoforms of 30% of all
      expressed genes are upregulated in NMD-deficient cells and that NMD targets all
      major splicing classes. Importantly, NMD-dependent effects are not restricted to
      premature termination codon+ isoforms but also involve an abundance of splicing
      events that do not generate premature termination codons. Supporting their
      functional importance, the latter events are associated with high intronic
      conservation. CONCLUSIONS: Our data demonstrate that NMD regulates alternative
      splicing outcomes through an intricate web of splicing regulators and that its
      loss leads to the deregulation of a panoply of splicing events, providing novel
      insights into its role in core- and tissue-specific regulation of gene
      expression. Thus, our study extends the importance of NMD from an mRNA quality
      pathway to a regulator of several layers of gene expression.

PMID- 22624610
TI  - Recent advances in the treatment of advanced renal cell carcinoma: towards
      multidisciplinary personalized care.
AB  - What's known on the subject? and What does the study add? With recent
      improvements in the prognosis for patients with metastatic renal cell carcinoma
      (mRCC), focus is now shifting towards maximising clinical benefit from targeted
      therapies. Factors other than efficacy data are increasingly being considered
      when selecting a treatment strategy, with a view towards optimising clinical
      outcomes. This review examines the development and efficacy of targeted agents
      for the management of mRCC and discusses the potential factors, including
      resistance mechanisms, sequential therapy, prognostic and predictive markers of
      response, and adverse event management, that may contribute to successful
      individually tallored treatment of patients with this disease. * Targeted agents
      have substantially improved outcomes for patients with metastatic renal cell
      carcinoma (mRCC). * Treatment focus is now shifting towards achieving a continuum
      of care such that long-term benefit and extended survival may be achieved through
      the optimal use of targeted agents. * To achieve this goal, a number of factors
      which impact on treatment selection and outcomes need to be considered when
      treating patients with mRCC, such as the optimal sequence of targeted therapies
      (and the related issue of resistance mechanisms). * Recent advances are also
      likely to impact on the future treatment of mRCC. Examples include the
      identification of predictive biomarkers as well as a consideration of patient
      risk profiles or the safety profile of the selected targeted agent. In addition,
      attention is focusing on re-defining the role of surgery for the treatment of RCC
      in the context of targeted therapies. * This review examines the recent and
      future advances that offer the potential for personalizing treatment by selecting
      the most appropriate treatment for each patient with a view towards optimizing
      clinical outcomes.

PMID- 22624611
TI  - TreeSnatcher plus: capturing phylogenetic trees from images.
AB  - BACKGROUND: Figures of phylogenetic trees are widely used to illustrate the
      result of evolutionary analyses. However, one cannot easily extract a machine
      readable representation from such images. Therefore, new software emerges that
      helps to preserve phylogenies digitally for future research. RESULTS:
      TreeSnatcher Plus is a GUI-driven JAVA application that semi-automatically
      generates a Newick format for multifurcating, arbitrarily shaped, phylogenetic
      trees contained in pixel images. It offers a range of image pre-processing
      methods and detects the topology of a depicted tree with adequate user
      assistance. The user supervises the recognition process, makes corrections to the
      image and to the topology and repeats steps if necessary. At the end TreeSnatcher
      Plus produces a Newick tree code optionally including branch lengths for
      rectangular and freeform trees. CONCLUSIONS: Although illustrations of
      phylogenies exist in a vast number of styles, TreeSnatcher Plus imposes no
      limitations on the images it can process with adequate user assistance. Given
      that a fully automated digitization of all figures of phylogenetic trees is
      desirable but currently unrealistic, TreeSnatcher Plus is the only program that
      reliably facilitates at least a semi-automatic conversion from such figures into
      a machine-readable format.

PMID- 22624612
TI  - Curcumin inhibits tongue carcinoma cells migration and invasion through
      downregulation of matrix metallopeptidase 10.
AB  - Squamous cell carcinoma (SCC) of tongue is an aggressive head and neck cancer
      with high propensity of regional spreading and invasion. Tongue carcinoma cells
      treated with curcumin, the major curcuminoid of the turmeric, demonstrated
      reduction in adhesion, migration, and invasion ability. High-throughput
      microarray analysis indicated that curcumin treatment suppressed matrix
      metallopeptidase 10 (MMP10) expression. MMP10 is overexpressed in tongue
      carcinoma tissues in comparison with the normal epithelia. Curcumin treatment on
      tongue carcinoma cell lines suppressed MMP10 expression at both mRNA and protein
      levels. Our results suggested that curcumin is a promising inhibitor to tongue
      cancer cells migration and invasion.

PMID- 22624613
TI  - Infantile hemangiopericytoma of the orbit treated with primary chemotherapy.
AB  - A 7-month-old female infant presented with proptosis of the left eye. Imaging
      showed an intraconal mass with marked post-contrast enhancement. Histopathology
      revealed a diagnosis of infantile hemangiopericytoma. The patient was treated
      with primary chemotherapy with no recurrence until 14 months after completion of
      treatment.

PMID- 22624614
TI  - Prenatal ultrasonographic detection of ophthalmic diseases.
AB  - Four patients with prenatal sonographic findings suggestive of ophthalmic
      pathology were detected in utero. The definitive diagnoses of infantile
      fibrosarcoma, persistent hyperplastic primary vitreous/persistent fetal
      vasculature, Fraser syndrome, and microphthalmia with coloboma and retrobulbar
      cyst were made postnatally. High-resolution intrauterine sonograms expedited
      ophthalmic referral and influenced prenatal planning.

PMID- 22624618
TI  - Tracking polypeptide folds on the free energy surface: effects of the chain
      length and sequence.
AB  - Characterization of the folding transition in polypeptides and assessing the
      thermodynamic stability of their structured folds are of primary importance for
      approaching the problem of protein folding. We use molecular dynamics simulations
      for a coarse grained polypeptide model in order to (1) obtain the equilibrium
      conformation diagram of homopolypeptides in a broad range of the chain lengths, N
      = 10, ..., 100, and temperatures, T (in a multicanonical ensemble), and (2)
      determine free energy profiles (FEPs) projected onto an optimal, so-called
      "natural", reaction coordinate that preserves the height of barriers and the
      diffusion coefficients on the underlying free energy hyper-surface. We then
      address the following fundamental questions. (i) How well does a kinetically
      determined free energy landscape of a single chain represent the polypeptide
      equilibrium (ensemble) behavior? In particular, under which conditions might the
      correspondence be lost, and what are the possible implications for the folding
      processes? (ii) How does the free energy landscape depend on the chain length
      (homopolypeptides) and the monomer interaction sequence (heteropolypeptides)? Our
      data reveal that at low T values equilibrium structures adopted by relatively
      short homopolypeptides (N < 60) are dominated by alpha-helical folds which
      correspond to the primary and secondary minima of the FEP. In contrast, longer
      homopolypeptides (N > 70), upon quasi-equilibrium cooling, fold preferentially in
      beta-bundles with small helical portions, while the FEPs exhibit no distinct
      global minima. Moreover, subject to the choice of the initial configuration, at
      sufficiently low T, essentially metastable structures can be found and prevail
      far from the true thermodynamic equilibrium. We also show that, by sequence
      enabling the polypeptide model, it is possible to restrict the chain to a very
      specific part of the configuration space, which results in substantial
      simplification and smoothing of the free energy landscape as compared to the case
      of the corresponding homopolypeptide.

PMID- 22624619
TI  - Estimation of the costs of cervical cancer screening, diagnosis and treatment in
      rural Shanxi Province, China: a micro-costing study.
AB  - BACKGROUND: Cost estimation is a central feature of health economic analyses. The
      aim of this study was to use a micro-costing approach and a societal perspective
      to estimate aggregated costs associated with cervical cancer screening, diagnosis
      and treatment in rural China. METHODS: We assumed that future screening programs
      will be organized at a county level (population ~250,000), and related treatments
      will be performed at county or prefecture hospitals; therefore, this study was
      conducted in a county and a prefecture hospital in Shanxi during 2008-9. Direct
      medical costs were estimated by gathering information on quantities and prices of
      drugs, supplies, equipment and labour. Direct non-medical costs were estimated
      via structured patient interviews and expert opinion. RESULTS: Under the base
      case assumption of a high-volume screening initiative (11,475 women screened
      annually per county), the aggregated direct medical costs of visual inspection,
      self-sampled careHPV (Qiagen USA) screening, clinician-sampled careHPV,
      colposcopy and biopsy were estimated as US$2.64,$7.49,$7.95,$3.90 and $5.76,
      respectively. Screening costs were robust to screening volume (<5% variation if
      2,000 women screened annually), but costs of colposcopy/biopsy tripled at the
      lower volume. Direct medical costs of Loop Excision, Cold-Knife Conization and
      Simple and Radical Hysterectomy varied from $61-544, depending on the procedure
      and whether conducted at county or prefecture level. Direct non-medical
      expenditure varied from $0.68-$3.09 for screening/diagnosis and $83-$494 for pre
      cancer/cancer treatment. CONCLUSIONS: Diagnostic costs were comparable to
      screening costs for high-volume screening but were greatly increased in lower
      volume situations, which is a key consideration for the scale-up phase of new
      programs. The study's findings will facilitate cost-effectiveness evaluation and
      budget planning for cervical cancer prevention initiatives in China.

PMID- 22624620
TI  - Evaluation of arterial structure and function in pediatric patients with end
      stage renal disease on dialysis and after renal transplantation.
AB  - CVD is a major cause of morbidity and mortality in pediatric patients with CKD.
      It is unclear whether vascular abnormalities in these patients are reversible,
      and if transplantation portends salutary effects on arterial function. We
      compared FMD, PWV, AI75, and CIMT in 15 dialysis (D), 14 transplant patients (T),
      and 15 controls (C), and their associations with cardiovascular risk factors.
      There was stepwise lower FMD (p < 0.001), higher AI75 (p < 0.001), higher PWV (p
      = 0.01), and higher CIMT SDS for age (p = 0.03) and height (p = 0.006) in the D
      group than T and C groups. FMD, PWV, and CIMT were unrelated to dialysis duration
      or time from transplantation. On multivariate analysis, group status was
      independently associated with FMD (beta = 3.15, p = 0.002), AI75 (beta = -5.95, p
      = 0.01), PWV (beta = -0.57, p = 0.07) and CIMT (beta = -0.02, p = 0.04) and CIMT
      SDS for height (beta = -0.541, p = 0.009). FMD is lower and AI75, PWV and CIMT
      are higher in pediatric patients maintained on D than T/C. T patients have
      similar AI75, PWV and CIMT to C although FMD remains reduced. These findings
      suggest that transplantation stabilizes or improves CKD associated arteriopathy.

PMID- 22624621
TI  - Transcranial magnetic stimulation as an investigative tool for motor dysfunction
      and recovery in stroke: an overview for neurorehabilitation clinicians.
AB  - RATIONALE: An improved understanding of motor dysfunction and recovery after
      stroke has important clinical implications that may lead to the design of more
      effective rehabilitation strategies for patients with hemiparesis. SCOPE:
      Transcranial magnetic stimulation (TMS) is a safe and painless tool that has been
      used in conjunction with other existing diagnostic tools to investigate motor
      pathophysiology in stroke patients. Since TMS emerged more than two decades ago,
      its application in clinical and basic neuroscience has expanded worldwide. TMS
      can quantify the corticomotor excitability properties of clinically affected and
      unaffected muscles and can probe local cortical networks as well as remote but
      functionally related areas. This provides novel insight into the physiology of
      neural circuits underlying motor dysfunction and brain reorganization during the
      motor recovery process. This important tool needs to be used with caution by
      clinical investigators, its limitations need to be understood, and the results
      should to be interpreted along with clinical evaluation in this patient
      population. SUMMARY: In this review, we provide an overview of the rationale,
      implementation, and limitations of TMS to study stroke motor physiology. This
      knowledge may be useful to guide future rehabilitation treatments by assessing
      and promoting functional plasticity.

PMID- 22624623
TI  - Global cooperation among diverse organizations to reduce illegal fishing in the
      Southern Ocean.
AB  - Illegal, unreported, and unregulated (IUU) fishing is prevalent globally and has
      detrimental effects on commercial fish stocks and nontarget species. Effective
      monitoring and enforcement aimed at reducing the level of IUU fishing in
      extensive, remote ocean fisheries requires international collaboration. Changes
      in trade and vessel activities further complicate enforcement. We used a web
      based survey of governmental and nongovernmental organizations engaged in
      reducing IUU fishing in the Southern Ocean to collect information on
      interorganizational collaborations. We used social-network analyses to examine
      the nature of collaborations among the identified 117 organizations engaged in
      reducing IUU fishing. International collaboration improved the ability to control
      and manage harvest of commercially important toothfish (Dissostichus spp.) stocks
      and reduced bycatch of albatrosses (Diomedeidae) and petrels (Procellariidae) in
      longlines of IUU fishing vessels. The diverse group of surveyed organizations
      cooperated frequently, thereby making a wide range of resources available for
      improved detection of suspected IUU vessels and trade flows, cooperation aimed at
      prosecuting suspected offenders or developing new policy measures. Our results
      suggest the importance of a central agency for coordination and for maintaining
      commonly agreed-upon protocols for communication that facilities collaboration.
      Despite their differences, the surveyed organizations have developed common
      perceptions about key problems associated with IUU fishing. This has likely
      contributed to a sustained willingness to invest in collaborations. Our results
      show that successful international environmental governance can be accomplished
      through interorganizational collaborations. Such cooperation requires trust,
      continuous funding, and incentives for actors to participate.

PMID- 22624622
TI  - Pulmonary surfactant coating of multi-walled carbon nanotubes (MWCNTs) influences
      their oxidative and pro-inflammatory potential in vitro.
AB  - BACKGROUND: Increasing concern has been expressed regarding the potential adverse
      health effects that may be associated with human exposure to inhaled multi-walled
      carbon nanotubes (MWCNTs). Thus it is imperative that an understanding as to the
      underlying mechanisms and the identification of the key factors involved in
      adverse effects are gained. In the alveoli, MWCNTs first interact with the
      pulmonary surfactant. At this interface, proteins and lipids of the pulmonary
      surfactant bind to MWCNTs, affecting their surface characteristics. Aim of the
      present study was to investigate if the pre-coating of MWCNTs with pulmonary
      surfactant has an influence on potential adverse effects, upon both (i) human
      monocyte derived macrophages (MDM) monocultures, and (ii) a sophisticated in
      vitro model of the human epithelial airway barrier. Both in vitro systems were
      exposed to MWCNTs either pre-coated with a porcine pulmonary surfactant
      (Curosurf) or not. The effect of MWCNTs surface charge was also investigated in
      terms of amino (-NH2) and carboxyl (-COOH) surface modifications. RESULTS: Pre
      coating of MWCNTs with Curosurf affects their oxidative potential by increasing
      the reactive oxygen species levels and decreasing intracellular glutathione
      depletion in MDM as well as decreases the release of Tumour necrosis factor alpha
      (TNF-alpha). In addition, an induction of apoptosis was observed after exposure
      to Curosurf pre-coated MWCNTs. In triple cell-co cultures the release of
      Interleukin-8 (IL-8) was increased after exposure to Curosurf pre-coated MWCNTs.
      Effects of the MWCNTs functionalizations were minor in both MDM and triple cell
      co-cultures. CONCLUSIONS: The present study clearly indicates that the pre
      coating of MWCNTs with pulmonary surfactant more than the functionalization of
      the tubes is a key factor in determining their ability to cause oxidative stress,
      cytokine/chemokine release and apoptosis. Thus the coating of nano-objects with
      pulmonary surfactant should be considered for future lung in vitro risk
      assessment studies.

PMID- 22624624
TI  - Microparticle detection in platelet products by three different methods.
AB  - BACKGROUND: Standardization of platelet-derived microparticle (PMP) enumeration
      by flow cytometry (FCM) is limited due to its intrinsic characteristics. Because
      of high clinical relevance of microparticle (MP) detection, standardization of MP
      assays is required. STUDY DESIGN AND METHODS: This prospective paired study
      analyzed 31 healthy blood donors (18 male, 13 female) and compared pre- and
      postdonation results of donors with results of plateletpheresis products by three
      different methods. PMP counts were analyzed by FCM using calibrated beads of
      defined diameter and annexin V-fluorescein isothiocyanate and CD41-phycoerythrin
      staining. MP activity was tested by prothrombinase assay (enzyme-linked
      immunosorbent assay [ELISA]) and a procoagulant phospholipid-dependent clotting
      time assay (STA-Procoag-PPL, Diagnostica Stago S.A.S.). RESULTS: PMP
      concentration was more than threefold higher in single-platelet units (SPUs) and
      resulted in higher PMP yields in SPUs compared to double-platelet units (DPUs).
      The ELISA and the procoagulant clotting assay also revealed a significant higher
      MP activity in SPUs compared to DPUs. The results of the procoagulation clotting
      assay correlated inversely with PMP counts obtained by FCM (r = -0.685, p <
      0.001) and with the MP activity measured by ELISA (r = -0.641, p < 0.001).
      CONCLUSION: Three different methods for MP detection showed good correlations of
      results, albeit the basis for MP analysis was different. Even if FCM is
      considered the "gold standard" of MP detection there are still technical
      limitations concerning detection of small MP. The procoagulant STA-Procoag-PPL
      assay and the prothrombinase ELISA assay could be useful additional MP tests.
      Regarding the interpretation of quantitative results of MPs, preanalytical
      conditions must be optimized and standardized.

PMID- 22624625
TI  - Palladium-catalyzed amidation of aryl halides using 2-dialkylphosphino-2'-alkoxyl
      1,1'-binaphthyl as ligands.
AB  - Palladium-catalyzed intermolecular C-N bond-forming reactions between aryl
      halides and amides are described using 2-dialkylphosphino-2'-alkoxyl-1,1'
      binaphthyl, which is both bulky and electron-rich, as the ligand. A variety of
      amides, including aliphatic and aromatic primary amides, lactams, and carbamates,
      were viable substrates for the amidation, which exhibited good functional group
      compatibility. By tuning the substituents at the 2,2'-position of 1,1'-binaphthyl
      of the ligand, the palladium-catalyzed amidation of bulky aryl halides was
      realized and this coupling reaction was used to synthesize 2-amino-2'-methoxy
      1,1'-binaphthyl in high yield.

PMID- 22624626
TI  - Incidence of severe congenital neutropenia in Sweden and risk of evolution to
      myelodysplastic syndrome/leukaemia.
AB  - Severe congenital neutropenia (SCN) is characterized by low blood neutrophil
      counts, early bacterial infections, and risk of leukaemia development. As yet, no
      population-based incidence estimates of SCN have been reported. Children less
      than 16 years of age with SCN were sought in Sweden during the 20-year period
      1987-2006 by a questionnaire to all Swedish Departments of Paediatrics and by
      reviewing the Swedish Health and Welfare Statistical Databases. Thirty-two
      patients were diagnosed with congenital neutropenia during this period. All
      received treatment with recombinant granulocyte-colony stimulating factor (G
      CSF). Twenty-one patients were diagnosed as SCN or probable SCN, corresponding to
      1.0 per 100,000 live births. Nine (43%) had ELANE mutations, four (19%) HAX1
      mutations and eight (38%) were children with disease of unknown genetic
      aetiology. Four out of 21 patients (19%) developed myelodysplastic
      syndrome/leukaemia and three (14%) died, all with leukaemia. The cumulative
      incidence of myelodysplastic syndrome/leukaemia was 31%. The observed incidence
      of SCN in this population-based study was higher than previously estimated,
      possibly because genetic testing now can identify SCN cases previously thought to
      be idiopathic or benign neutropenia. The risk of developing myelodysplastic
      syndrome/leukaemia is considerable. ELANE mutations are the most commonly
      identified genetic defects.

PMID- 22624628
TI  - RNA and DNA association to zwitterionic and charged monolayers at the air-liquid
      interface.
AB  - The objective of this work is to establish under which conditions short RNA
      molecules (similar to miRNA) associate with zwitterionic phospholipids and how
      this differs from the association with cationic surfactants. We study how the
      base pairing (i.e., single stranded versus double stranded nucleic acids) and the
      length of the nucleic acid and the charge of the lipid/surfactant monolayer
      affect the association behavior. For this purpose, we study the adsorption of
      nucleic acids to monolayers composed of dipalmitoyl phosphatidylcholine (DPPC) or
      dioctadecyl-dimethyl-ammoniumbromide (DODAB) using the surface film balance,
      neutron reflectometry, and fluorescence microscopy. The monolayer studies with
      the surface film balance suggested that short single-stranded ssRNA associates
      with liquid expanded zwitterionic phospholipid monolayers, whereas less or no
      association is detected for double-stranded dsRNA and dsDNA. In order to quantify
      the interaction and to determine the location of the nucleic acid in the
      lipid/surfactant monolayer we performed neutron reflectometry measurements. It
      was shown that ssRNA adsorbs to and penetrates the liquid expanded monolayers,
      whereas there is no penetration of nucleic acids into the liquid condensed
      monolayer. No adsorption was detected for dsDNA to zwitterionic monolayers. On
      the basis of these results, we propose that the association is driven by the
      hydrophobic interactions between the exposed hydrophobic bases of the ssRNA and
      the hydrocarbon chains of the phospholipids. The addition of ssRNA also
      influences domain formation in the DPPC monolayer, leading to fractal-like
      interconnected domains. The experimental results are discussed in terms of the
      implication for biological processes and new leads for applications in medicine
      and biotechnology.

PMID- 22624629
TI  - The future of community-centred health services in Australia - an alternative
      view.
AB  - Community-centred healthcare works in conjunction with hospital-centred
      healthcare. Both have strengths and limitations. Community-centred healthcare has
      been demonstrated to be a more cost-efficient and cost-effective alternative to
      hospital-centred care at best in a limited fashion. If hospital-centred services
      dominate healthcare services in Australia, as argued previously in this journal,
      then this has not extended to maintenance of inpatient bed provision. The author,
      as a hospital-based emergency specialist, has observed case load and models of
      care in hospitals and emergency departments for 30 years and is sceptical of
      promises to substantially further decrease emergency department demand and acute
      bed requirements. The real benefits of community, primary and preventive care
      should not be over sold.

PMID- 22624627
TI  - P450 monooxygenases (P450ome) of the model white rot fungus Phanerochaete
      chrysosporium.
AB  - Phanerochaete chrysosporium, the model white rot fungus, has been the focus of
      research for the past about four decades for understanding the mechanisms and
      processes of biodegradation of the natural aromatic polymer lignin and a broad
      range of environmental toxic chemicals. The ability to degrade this vast array of
      xenobiotic compounds was originally attributed to its lignin-degrading enzyme
      system, mainly the extracellular peroxidases. However, subsequent physiological,
      biochemical, and/or genetic studies by us and others identified the involvement
      of a peroxidase-independent oxidoreductase system, the cytochrome P450
      monooxygenase system. The whole genome sequence revealed an extraordinarily large
      P450 contingent (P450ome) with an estimated 149 P450s in this organism. This
      review focuses on the current status of understanding on the P450 monooxygenase
      system of P. chrysosproium in terms of pre-genomic and post-genomic
      identification, structural and evolutionary analysis, transcriptional regulation,
      redox partners, and functional characterization for its biodegradative potential.
      Future research on this catalytically diverse oxidoreductase enzyme system and
      its major role as a newly emerged player in xenobiotic metabolism/degradation is
      discussed.

PMID- 22624630
TI  - Digital technology use among disadvantaged Australians: implications for
      equitable consumer participation in digitally-mediated communication and
      information exchange with health services.
AB  - OBJECTIVE: To present research findings on access to, and use of, digital
      information and communication technologies (ICTs) by Australians from lower
      income and disadvantaged backgrounds to determine implications for equitable
      consumer access to digitally-mediated health services and information. METHODS:
      Focus groups were held in 2008-09 with 80 residents from lower income and
      disadvantaged backgrounds in South Australia, predominantly of working- and
      family-formation age (25 to 55 years). Qualitative analysis was conducted on a
      priori and emergent themes to describe dominant categories. RESULTS: Access to,
      and use of, computers, the Internet and mobile phones varied considerably in
      extent, frequency and quality within and across groups due to differences in
      abilities, resources and life experience. Barriers and facilitators included
      English literacy (including for native speakers), technological literacy,
      education, income, housing situation, social connection, health status,
      employment status, and trust. Many people gained ICT skills by trial and error or
      help from friends, and only a few from formal programs, resulting in varied
      skills. CONCLUSION: The considerable variation in ICT access and use within lower
      income and disadvantaged groups must be acknowledged and accommodated by health
      initiatives and services when delivering digitally-mediated consumer-provider
      interaction, online health information, or online self-management of health
      conditions. If services require consumers to participate in a digitally-mediated
      communication exchange, then we suggest they might support skills and technology
      acquisition, or provide non-ICT alternatives, in order to avoid exacerbating
      health inequities.

PMID- 22624631
TI  - The journey to total hip or knee replacement.
AB  - OBJECTIVES: Despite the incidence of joint replacements in Australia, there is a
      paucity of information regarding how patients progress from their referral to
      their surgery. The aim of this study was to describe a patient pathway from
      referral to receipt of total hip replacement (THR) or total knee replacement
      (TKR) surgery in South Australian public hospitals. METHODS: Patient perspectives
      of the pathway to THR and TKR surgery were obtained via a postal survey (n=450)
      and hospital employee perspectives were attained via semi-structured interviews
      (n=19). Survey data were analysed using descriptive statistics and interview data
      were analysed thematically. RESULTS: A typical patient pathway to THR and TKR
      surgery can be divided into two distinct phases; referral-to-initial appointment
      (9-24 months), and initial appointment-to-surgery (12-15 months). This gives an
      overall waiting period between 2 and 3 years for THR or TKR surgery. CONCLUSIONS:
      Waiting times for THR and TKR surgery reported in this study were longer than
      other reports in the literature. Current Australian health policy does not
      consider the first (and longest) phase of the patient pathway. Excluding this
      initial phase could be generating an erroneous perception of the patient pathway
      to THR or TKR surgery, possibly leading to poorly considered health reforms.

PMID- 22624632
TI  - Leadership collaboration during health reform: an action learning approach with
      an interagency group of executives in Tasmania.
AB  - OBJECTIVE: To use an action learning approach to encourage a group of executive
      leaders, responsible for the implementation of a state health reform agenda, to
      consider the leadership required to drive improvement in healthcare services.
      METHODS: Based on an assertion that knowledge is co-produced and that
      deliberative and structured conversation can be a mechanism to drive change, an
      action learning approach was used to facilitate an interagency group of executive
      leaders, responsible for the implementation of a state health reform agenda, who
      were encouraged to consider the leadership required to drive improvement in
      healthcare services. RESULTS: It was difficult to assert how the group
      contributed specifically to the implementation of the health reform agenda but
      individuals gained insights and there was informal resolution of institutional
      tensions and differences. The method may provide new knowledge to the reform
      process over time. CONCLUSIONS: Getting the participants together was
      challenging, which may reflect the reality of time-poor executives, or a low
      commitment to giving time to structured and deliberative informal dialogue.
      Further work is required to test this thesis and the action learning approach
      with other parts of healthcare workforce.

PMID- 22624633
TI  - Safety of non-medically led primary maternity care models: a critical review of
      the international literature.
AB  - The Australian government has announced major reforms with the move to a primary
      maternity care model. The direction of the reforms remains contentious; with the
      Australian Medical Association warning that the introduction of non-medically led
      services will compromise current high standards in maternity services and
      threaten the safety of mothers and babies. The purpose of this paper is to
      conduct a critical review of the literature to determine whether there is
      convincing evidence to support the safety of non-medically led models of primary
      maternity care. Twenty-two non-randomised international studies were included
      representing midwifery-led care, birth centre care and home birth. Comparative
      outcome measurements included: perinatal mortality; perinatal morbidity; rates of
      medical intervention in labour; and antenatal and intrapartum referral and
      transfer rates. Findings support those of the three Cochrane reviews, that there
      is sufficient international evidence to support the conclusion of no difference
      in outcomes associated with low risk women in midwifery-led, birth centre and
      home birth models compared with standard hospital or obstetric care. These
      findings are limited to services involving qualified midwives working within
      rigorous exclusion, assessment and referral guidelines, limiting the number of
      urgent intrapartum transfers that come with increased risk of perinatal
      mortality.

PMID- 22624634
TI  - Breaking up is hard to do: why disinvestment in medical technology is harder than
      investment.
AB  - Healthcare technology is a two-edged sword - it offers new and better treatment
      to a wider range of people and, at the same time, is a major driver of increasing
      costs in health systems. Many countries have developed sophisticated systems of
      health technology assessment (HTA) to inform decisions about new investments in
      new healthcare interventions. In this paper, we question whether HTA is also the
      appropriate framework for guiding or informing disinvestment decisions. In
      exploring the issues related to disinvestment, we first discuss the various HTA
      frameworks which have been suggested as a means of encouraging or facilitating
      disinvestment. We then describe available means of identifying candidates for
      disinvestment (comparative effectiveness research, clinical practice variations,
      clinical practice guidelines) and for implementing the disinvestment process
      (program budgeting and marginal analysis (PBMA) and related techniques). In
      considering the possible reasons for the lack of progress in active
      disinvestment, we suggest that HTA is not the right framework as disinvestment
      involves a different decision making context. The key to disinvestment is not
      just what to stop doing but how to make it happen - that is, decision makers need
      to be aware of funding disincentives.

PMID- 22624635
TI  - Coordination of care in Australian mental health policy.
AB  - OBJECTIVE: To review Australian mental health initiatives involving coordination
      of care. METHODS: Commonwealth government websites were systematically searched
      for mental health policy documents. Database searches were also conducted using
      the terms 'coordination' or 'integration' and 'mental health' or 'mental illness'
      and 'Australia'. We assessed the extent to which informational, relational and
      management continuity have been addressed in three example programs. RESULTS: The
      lack of definition of coordination at the policy level reduces opportunities for
      developing actionable and measurable programs. Of the 51 mental health
      initiatives identified, the three examples studied all demonstrated some use of
      the dimensions of continuity to facilitate coordination. However, problems with
      funding, implementation, evaluation and competing agendas between key
      stakeholders were barriers to improving coordination. CONCLUSIONS: Coordination
      is possible and can improve both relationships between providers and care
      provided. However, clear leadership, governance and funding structures are needed
      to manage the challenges encountered, and evaluation using appropriate outcome
      measures, structured to assess the elements of continuity, is necessary to detect
      improvements in coordination.

PMID- 22624636
TI  - Do smoke-free environment policies reduce smoking on hospital grounds? Evaluation
      of a smoke-free health service policy at two Sydney hospitals.
AB  - OBJECTIVE: To evaluate the compliance of hospital staff, inpatients and visitors
      with Sydney South West Area Health Service's Smoke-free Environment Policy.
      METHODS: Six sites were observed at two Sydney hospitals 2 weeks before
      implementation of the policy and at 2 weeks, 6 months, 12 months, 18 months and 2
      years after implementation. RESULTS: There was an overall significant 36%
      (P<=0.05) reduction in observed smoking incidents on hospital grounds 2 years
      after implementation. Two years after implementation, observed smoking incidents
      reduced by 44% (P<=0.05) in staff, 37% (P<=0.05) in visitors and remained
      unchanged among inpatients. CONCLUSIONS AND IMPLICATIONS: The Smoke-free
      Environment Policy was effective in reducing visitors and staff observed smoking
      on hospital grounds, but had little effect on inpatients' smoking. Identifying
      strategies to effectively manage nicotine addiction and promote cessation amongst
      hospital inpatients remains a key priority.

PMID- 22624637
TI  - Variation in the adoption of patient safety practices among New Zealand district
      health boards.
AB  - OBJECTIVE: To investigate the adoption and impact of quality improvement measures
      in New Zealand hospitals. METHOD: Structured interviews with quality and safety
      managers of District Health Boards (DHBs). Correlation of use of measures with
      adjusted 30-day mortality data. RESULTS: Eighteen of New Zealand's 21 DHBs
      participated in the survey. Structural or policy measures to improve patient
      safety, such as credentialing and event reporting procedures, had been introduced
      into all DHBs, whereas changes to general clinical processes such as medicine
      reconciliation, falls prevention interventions and disease-specific management
      guidelines were less consistently used. There was no meaningful correlation
      between risk-adjusted mortality rates for three common medical conditions and
      related quality measures. CONCLUSION: Widespread variation exists among New
      Zealand DHBs in their adoption of quality and safety practices, especially in
      relation to clinical processes of care.

PMID- 22624639
TI  - Addressing the workplace needs of Western Australian midwives: a Delphi study.
AB  - OBJECTIVE: To determine the workplace needs of Western Australian midwives
      working in public metropolitan secondary hospitals. METHOD: Using a three-round
      Delphi approach, Round 1 incorporated focus groups and a questionnaire. Fifteen
      focus groups were conducted with midwives also having the option of contributing
      through an open-ended questionnaire. During Round 2, 38 items reflecting seven
      themes were prioritised with a final ranking performed in Round 3. In total, 114
      midwives participated in Round 1, 72 in Round 2 and 89 in Round 3. RESULTS:
      During Round 1, workplace needs identified as being met included: working across
      all areas of midwifery; ability to work in areas of interest; opportunity to work
      with low to moderate risk women; supportive colleagues; accessible parking;
      hospital close to home and friendly work atmosphere. Round 2 items revealed the
      five top unmet needs as: adequate midwifery staff coverage; access to maintained
      equipment; competitive pay scales; patient safety issues and opportunities to
      implement midwifery models. The top ranked needs from Round 3 included:
      recognising the unpredictable nature of midwifery services; provision of
      competent medical coverage, and adequate midwifery staff coverage. CONCLUSIONS:
      Demand for maternity services is unpredictable; however, in order to maintain a
      sustainable maternity workforce, WA midwives' prioritised needs would suggest
      health management focus upon expanding the availability of midwifery models of
      care, fostering flexible working conditions and ensuring collaboration between
      maternity health professionals occurs within clinically safe staffing levels.

PMID- 22624638
TI  - Australian maternity reform through clinical redesign.
AB  - The current Australian national maternity reform agenda focuses on improving
      access to maternity care for women and their families while preserving safety and
      quality. The caseload midwifery model of care offers the level of access to
      continuity of care proposed in the reforms however the introduction of these
      models in Australia continues to meet with strong resistance. In many places
      access to caseload midwifery care is offered as a token, usually restricted to
      well women, within limited metropolitan and regional facilities and where
      available, places for women are very small as a proportion of the total service
      provided. This case study outlines a major clinical redesign of midwifery care at
      a metropolitan tertiary referral maternity hospital in Sydney. Caseload midwifery
      care was introduced under randomised trial conditions to provide midwifery care
      to 1500 women of all risk resulting in half of the publicly insured women
      receiving midwifery group practice care. The paper describes the organisational
      quality and safety tools that were utilised to facilitate the process while
      discussing the factors that facilitated the process and the barriers that were
      encountered within the workforce, operational and political context.

PMID- 22624640
TI  - Workplace abuse among correctional health professionals in New South Wales,
      Australia.
AB  - OBJECTIVE: Studies have found that health workers are at elevated risk of being
      abused while at work. Little is known, however, about workplace abuse among
      correctional health professionals. We implemented a cross-sectional study to
      investigate the prevalence, sources and consequences of workplace abuse among
      correctional health professionals in New South Wales, Australia. METHODS All
      employees of Justice Health (a statutory health corporation) were invited to
      complete a self-administered survey, which was delivered via the internet. Among
      nurses, medical doctors and allied health professionals, 299 usable surveys were
      returned; a response rate of 42%. RESULTS: In the preceding 3 months, 76% of
      participants had personally experienced some form of abuse in their workplace,
      all but one of whom recalled verbal abuse. Only 16% reported physical abuse.
      Seventy per cent reported feeling safe in their workplace. Patients were
      identified as the main perpetrators of abuse, followed by fellow health staff.
      Participants felt that incidents of workplace abuse increased their potential to
      make errors while providing care to patients and reduced their productivity while
      at work. CONCLUSIONS: Compared with health workers who practise in a community
      setting, the risk of physical abuse among correctional health professionals
      appears to be low.

PMID- 22624641
TI  - Why are junior doctors deterred from choosing a surgical career?
AB  - OBJECTIVE: To identify the reasons why interns would not choose a surgical
      career. METHODS: This qualitative study used semi-structured telephone interviews
      to explore the future career choices of 41 junior doctors (14 men, 27 women).
      Doctors were asked to identify specialties they would not take up, and state why
      this was the case. RESULTS: Thirty (73.2%) of the 41 interns nominated surgery as
      a specialty they would not choose. Themes relating to reasons for not wanting to
      pursue a surgical career included the lifestyle associated with surgery (66.7%),
      the culture within the surgical work environment (53.3%), the lack of interest in
      performing surgical work (36.7%), and the training requirements associated with
      surgery (33.3%). Both sexes had similar reasons for not wanting to choose a
      surgical career; but additionally, women referred to the male domination of
      surgery, and the difficulty and inflexibility of the training program as
      deterrents. CONCLUSIONS: Efforts are needed to promote interest in surgery as a
      career especially for women, to improve the surgical work environment so that
      medical students and junior doctors have exposure to positive role models and
      surgical placements, and to provide a more flexible approach to surgical
      training.

PMID- 22624642
TI  - Bullying in the Australian medical workforce: cross-sectional data from an
      Australian e-Cohort study.
AB  - OBJECTIVE: This study aimed to describe the prevalence of perceived workplace
      bullying in the Australian medical workforce, and investigate the relationship
      between workplace bullying and job satisfaction, health status, and current and
      planned medical workforce participation. METHODS: An electronic cross-sectional
      survey of doctors currently in the paid workforce, conducted between April 2008
      and October 2009, was nested within a longitudinal cohort study investigating
      factors affecting the recruitment and retention of the Australian medical
      workforce. To address the specific aims of this study, a subset of questions in
      the survey investigated the prevalence of self-reported bullying; physical and
      mental health; workforce participation patterns; job satisfaction; and job
      stressors. RESULTS: Seven hundred and forty-seven participants responded to the
      bullying question and were included in this analysis. Twenty-five percent of
      participants reported being bullied in the last 12 months. There were no
      differences in the reported rates of bullying across age groups, sex and country
      of medical qualification. Bullied doctors were least satisfied with their jobs
      (P<0.001), had taken more sick leave in the last 12 months (P<0.001), and were
      more likely to be planning to decrease the number of hours worked in medicine in
      the next 12 months (P=0.01) or ceasing direct patient care in the next 5 years
      (independent of their age or the number of hours currently worked in patient
      care) (P=0.006). CONCLUSIONS: Our findings suggest that Australian doctors,
      independent of age or sex, have experienced workplace bullying, and although no
      conclusions can be made about causal pathways, there were strong associations
      between this exposure and poorer health and wellbeing, and on remaining in the
      medical workforce.

PMID- 22624643
TI  - Effect of a chronic disease management service for patients with diabetes on
      hospitalisation and acute care costs.
AB  - OBJECTIVE: To evaluate the effect of a diabetes-management program for patients
      with type 2 diabetes and related comorbidities on acute healthcare utilisation
      and costs. METHODS: This was a retrospective administrative dataset analysis
      using data for patients enrolled from 2007 to 2008. Inpatient admissions for
      diabetes-related conditions were compared before, during and following enrolment.
      Costs per episode were estimated from Weighted Inlier Equivalent Separations
      (WIES) funding. A cost model was then developed based on admission rates per 100
      patients. RESULTS: Data were retrieved for 357 patients; 49% males, mean age 62
      years. The mean per-patient cost of the program was AU$524 (s.d. $213). The mean
      cost of an inpatient admission was $4357(95% CI 2743-5971) pre-enrolment and
      $4396 (95% CI 2888-5904) post-enrolment. Following program completion the annual
      costs (per 100 patients) for managing 'diabetes with multiple complications' and
      hypoglycaemia decreased from $10181 to $1710 and $9947 to $7800. In contrast, the
      annual cost of cardiovascular disorders increased from $14485 to $40071 per 100
      patients. CONCLUSIONS: In the short-term diabetes-management programs for
      patients with comorbid vascular disease may reduce hospital utilisation for
      diabetes but not for cardiovascular disease. Longer-term follow-up is needed to
      determine whether intensive management of vascular complications can reduce
      costs.

PMID- 22624644
TI  - Knowing the people planning: measuring change in mental health services.
AB  - This article describes the underlying philosophy of knowing the people planning
      (KPP) and gives an example of a practical approach to measure people's recovery
      in terms of consumer identified outcomes leading to the improvement in the
      effectiveness of mental health and addiction services in Hawke's Bay. KPP
      provided a valuable approach to planning service delivery by measuring key
      variables of service delivery based on consumer determined key features and a
      means to describe the quality improvements implemented in services in Hawke's
      Bay. Practitioners were directly involved; the key was to identify gaps and work
      with stakeholders to create solutions to facilitate better and improved recovery
      outcomes.

PMID- 22624645
TI  - Research performance evaluation: the experience of an independent medical
      research institute.
AB  - BACKGROUND: Evaluation of the social and economic outcomes of health research
      funding is an area of intense interest and debate. Typically, approaches have
      sought to assess the impact of research funding by medical charities or regional
      government bodies. Independent research institutes have a similar need for
      accountability in investment decisions but have different objectives and funding,
      thus the existing approaches are not appropriate. METHODS: An evaluation
      methodology using eight indicators was developed to assess research performance
      across three broad categories: knowledge creation; inputs to research; and
      commercial, clinical and public health outcomes. The evaluation approach was
      designed to provide a balanced assessment across laboratory, clinical and public
      health research. RESULTS AND DISCUSSION: With a diverse research agenda supported
      by a large number of researchers, the Research Performance Evaluation process at
      the Murdoch Childrens Research Institute has, by necessity, been iterative and
      responsive to the needs of the Institute and its staff. Since its inception 5
      years ago, data collection systems have been refined, the methodology has been
      adjusted to capture appropriate data, staff awareness and participation has
      increased, and issues regarding the methodology and scoring have been resolved.
      CONCLUSIONS: The Research Performance Evaluation methodology described here
      provides a fair and transparent means of disbursing internal funding. It is also
      a powerful tool for evaluating the Institute's progress towards achieving its
      strategic goals, and is therefore a key driver for research excellence.

PMID- 22624646
TI  - An evaluation framework for non-medical prescribing research.
AB  - Without robust and credible evidence for the benefits in health outcomes of non
      medical prescribing, widespread implementation will be challenging. Our aim is to
      develop a consistent evaluation framework that could be applied to non-medical
      prescribing research. An informal collaboration was initiated in 2008 by a group
      of pharmacists from Australia and New Zealand to assist in information sharing,
      pilot design, methodologies and evaluation for pharmacist prescribing. Different
      pilots used different models, methodologies and evaluation. It was agreed that
      the development of a consistent evaluation framework to be applied to future
      research on non-medical prescribing was required. The framework would help to
      align the outcomes of different research pilots and enable the comparison of
      endpoints to determine the effectiveness of a non-medical prescribing
      intervention.

PMID- 22624647
TI  - Validity of anaesthetic complication coding data as a clinical indicator.
AB  - Clinical indicators using routinely collected International Statistical
      Classification of Diseases, Australian Modification (ICD-10-AM) data offer
      promise as tools for improvement of quality. The ICD-10-AM is the coding system
      used by Australian administrators to summarise information from the clinical
      record to describe a patient's hospital encounter. The use of anaesthesia
      complications as coded by this system has been proposed by two jurisdictions as a
      monitor of the quality of anaesthetic services. We undertook a review of cases
      identified by such indicators in a large tertiary hospital. Our results indicate
      the anaesthesia indicator dataset proposed by the Victorian and Queensland Health
      departments appears to have little clinical or quality improvement relevance.

PMID- 22624648
TI  - Successfully reforming orthopaedic outpatients.
AB  - Since 2005, Barwon Health has successfully reformed its orthopaedic outpatient
      service to address the following issues: increasing number of referrals,
      inefficient referral management and triage, long waiting times for non-urgent
      appointments, high 'Did Not Attend' (DNA) rates and poor utilisation of
      conservative therapies before referral to surgeon. Numerous strategies have been
      implemented including: waiting list audits, triage guidelines, physiotherapy-led
      clinics, a DNA policy, an orthopaedic lead nurse role and a patient-focussed
      booking system. There has been a 66% reduction in the number of patients waiting
      for their first appointment; an 87% reduction in the waiting time from referral
      to first appointment; a 10% reduction in new patient DNAs; and more efficient
      referral management and communication processes. Patients are now seen in
      clinically appropriate time frames and offered earlier access to a wider range of
      conservative treatments.

PMID- 22624649
TI  - Suicide in men with testis cancer.
AB  - Depression, anxiety and aggression are documented in testis cancer patients and
      can result in death from suicides; however, their risk of suicide is not defined.
      We report suicide rates among testis cancer patients in the USA and determine
      factors associated with higher rates. We used the Surveillance, Epidemiology, and
      End Results (SEER) database maintained by the National Cancer Institute to
      identify patients diagnosed with testis cancer between 1995 and 2008.
      Multivariate analysis was used to assess factors affecting suicide rate. Among
      23,381 patients followed for 126,762 person-years, suicide rate was 26.0 per
      100,000 person-years, with the average corresponding rate in the US population
      aged 25-44 years being 21.5 per 100,000 person-years; the calculated standardised
      mortality ratio for death by suicide was 1.2 [95% confidence interval (CI): 1.1
      2.1]. The standardised mortality ratio for suicide was 1.5 (95% CI: 1.1-2.1) in
      ages less than 30 years, and 1.8 (95% CI: 1.3-2.4) in men of races other than
      White and Black. Other patient and disease characteristics were not predictive.
      In conclusion, patients with testis cancer have a 20% increase in the risk of
      suicide over that of the general population, and races other than White and Black
      and younger patients may commit suicide at higher rates.

PMID- 22624650
TI  - Identification of a novel structure in heparin generated by sequential oxidative
      reductive treatment.
AB  - Unfractionated heparin is isolated from animal organs, predominantly porcine
      intestinal mucosa, and goes through an extensive process of purification before
      it can be used for pharmaceutical purposes. While the structural
      microheterogeneity of heparin is predominantly biosynthetically imprinted in the
      Golgi, subsequent steps involved in the purification and manufacture of
      commercial heparin can lead to the introduction of additional modifications.
      Postheparin crisis of 2008, it has become increasingly important to identify what
      additional structural diversity is introduced as a function of the purification
      process and thus can be determined as being heparin-related, as opposed to being
      an adulterant or contaminant, e.g., oversulfated chondroitin sulfate. Our study
      focuses on the identification of a previously unreported structure in heparin
      that arises due to specific steps used in the manufacturing process. This
      structure was initially observed as a disaccharide peak in a complete enzymatic
      digest of heparin, but its presence was later identified in the NMR spectra of
      intact heparin as well. Structural elucidation experiments involved isolation of
      this structure and analysis based on multidimensional NMR and liquid
      chromatography coupled with mass spectrometry (LC-MS). Heparin was also subjected
      to specific chemical reactions to determine which steps in the manufacturing
      process are responsible for this novel structure. Our results allowed for the
      definitive assignment of the structure of this novel process-related modification
      and enabled an identification of the putative steps in the process that give rise
      to the structure.

PMID- 22624651
TI  - A systematic screen reveals new elements acting at the G2/M cell cycle control.
AB  - BACKGROUND: The major cell cycle control acting at the G2 to mitosis transition
      is triggered in all eukaryotes by cyclin-dependent kinases (CDKs). In the fission
      yeast Schizosaccharomyces pombe the activation of the G2/M CDK is regulated
      primarily by dephosphorylation of the conserved residue Tyr15 in response to the
      stress-nutritional response and cell geometry sensing pathways. To obtain a more
      complete view of the G2/M control we have screened systematically for gene
      deletions that advance cells prematurely into mitosis. RESULTS: A screen of 82%
      of fission yeast non-essential genes, comprising approximately 3,000 gene
      deletion mutants, identified 18 genes that act negatively at mitotic entry, 7 of
      which have not been previously described as cell cycle regulators. Eleven of the
      18 genes function through the stress response and cell geometry sensing pathways,
      both of which act through CDK Tyr15 phosphorylation, and 4 of the remaining genes
      regulate the G2/M transition by inputs from hitherto unknown pathways. Three
      genes act independently of CDK Tyr15 phosphorylation and define additional
      uncharacterized molecular control mechanisms. CONCLUSIONS: Despite extensive
      investigation of the G2/M control, our work has revealed new components of
      characterized pathways that regulate CDK Tyr15 phosphorylation and new components
      of novel mechanisms controlling mitotic entry.

PMID- 22624652
TI  - Nutritional treatment of aged individuals with Alzheimer disease living at home
      with their spouses: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Nutritional status often deteriorates in Alzheimer's disease (AD).
      Less is known about whether nutritional care reverses malnutrition and its
      harmful consequences in AD. The aim of this study is to examine whether
      individualized nutritional care has an effect on weight, nutrition, health,
      physical functioning, and quality of life in older individuals with AD and their
      spouses living at home. METHODS: AD patients and their spouses (aged > 65 years)
      living at home (n = 202, 102 AD patients) were recruited using central AD
      registers in Finland. The couples were randomized into intervention and control
      groups. A trained nutritionist visited intervention couples 4-8 times at their
      homes and the couples received tailored nutritional care. When necessary, the
      couples were given protein and nutrient-enriched complementary drinks. All
      intervention couples were advised to take vitamin D 20 MUg/day. The intervention
      lasted for one year. The couples of the control group received a written guide on
      nutrition of older people. Participants in the intervention group were assessed
      every three months. The primary outcome measure is weight change. Secondary
      measures are the intake of energy, protein, and other nutrients, nutritional
      status, cognition, caregiver's burden, depression, health related quality of life
      and grip strength. DISCUSSION: This study provides data on whether tailored
      nutritional care is beneficial to home-dwelling AD patients and their spouses.
      TRIAL REGISTRATION: ACTRN 12611000018910.

PMID- 22624653
TI  - Laparoscopic Heller's cardiomyotomy achieved lesser recurrent dysphagia with
      better quality of life when compared with endoscopic balloon dilatation for
      treatment of achalasia.
AB  - Achalasia is a rare primary motility disorder of esophagus; treatments include
      endoscopic balloon dilatation (EBD) and laparoscopic Heller's cardiomyotomy (LC).
      This study compared EBD versus LC for treatment of achalasia with focus on
      quality of life (QoL) and prevalence of post-treatment gastroesophageal reflux
      disease. This was a retrospective cohort study of all patients diagnosed with
      achalasia older than 16 treated with either EBD or LC from January 1998 to April
      2008. Patients' demographic data, comorbidities, postintervention GERD symptoms,
      QoL, recurrence of dysphagia, reintervention rate, hospital stay, and time to
      resumption of diet were collected. Sixty-eight patients were recruited into the
      study (EBD n= 50; LC n= 18). A significant improvement in QoL was found in
      patients undergoing LC (0.917 vs. 0.807, P= 0.006). A higher proportion of
      patients treated with EBD developed post-treatment gastroesophageal reflux
      symptoms (60.5% vs. 43.8%) when compared with LC, although statistically
      insignificant (P= 0.34). Patients treated with balloon dilatation had a greater
      percentage of recurrence of dysphagia (55.1% vs. 26.7%; P= 0.235) and need of
      reintervention (42.1% vs. 9.1%; P= 0.045). However, these patients had a shorter
      median hospital stay (1d [range 0-4]) and earlier resumption of diet (0d [range 0
      3]). Although EBD is associated with a quicker perioperative recovery, LC
      accomplished a better QoL, lower incidence of recurrence of dysphagia, and need
      of reintervention after treatment for achalasia.

PMID- 22624654
TI  - Insect repellents and associated personal protection for a reduction in human
      disease.
AB  - Personal protection measures against biting arthropods include topical insect
      repellents, area repellents, insecticide-treated bednets and treated clothing.
      The literature on the effectiveness of personal protection products against
      arthropods is mainly limited to studies of prevention of bites, rather than
      prevention of disease. Tungiasis was successfully controlled by application of
      topical repellents and scrub typhus was reduced through the use of treated
      clothing. Successful reduction of leishmaniasis was achieved through the use of
      topical repellents, treated bednets and treated clothing in individual studies.
      Malaria has been reduced by the use of insecticide-treated bednets (ITN), certain
      campaigns involving topical repellents, and the combination of treated bednets
      and topical repellents. Although area repellents such as mosquito coils are used
      extensively, their ability to protect humans from vector-transmitted pathogens
      has not been proven. Taken together, the literature indicates that personal
      protection measures must be used correctly to be effective. A study that showed
      successful control of malaria by combining treated bednets and topical repellents
      suggests that combinations of personal protection measures are likely to be more
      effective than single methods. Implementation of successful programmes based on
      personal protection will require a level of cooperation commonly associated with
      other basic societal functions, such as education and food safety.

PMID- 22624655
TI  - Anxiety and depression among AL amyloidosis patients: the role of cardiac
      symptoms.
AB  - Light-chain (AL) amyloidosis has the worst prognosis out of the different forms
      of cardiac amyloidosis, However, data are not available about the incidence of
      the disease-related psychological impact of AL amyloidosis in this population. In
      particular, no data are available about the impact of diagnosis communication or
      about the impact of cardiac symptom onset and severity on anxiety and depression
      levels among AL patients. AIM: To evaluate the role of time that has passed since
      the diagnosis was communicated, time that has passed since the onset of cardiac
      symptoms, and actual cardiac symptom severity have on level of anxiety,
      depression and psychological stress among cardiology patients with AL. Thirty-two
      AL patients with cardiac-related symptoms were administered General Health
      Questionnaire, State-Trait Anxiety Inventory and Centre for Epidemiological Study
      Depression Scale. Clinical variables such as months gone by since diagnosis,
      months gone by since the onset of cardiac symptoms, and cardiac symptom severity
      (New York Heart Association (NYHA) class) were measured. Troponin, NT-pro BNP
      levels, Mayo Stage and echocardiographic characteristics were also collected.
      RESULTS: According to questionnaire normative values, AL patients presented
      severe psychological distress, severe anxiety and clinical depression. Moreover,
      anxiety levels were determined by psychological distress (p < 0.001) and months
      gone by since the onset of cardiac symptoms (p < 0.01) while depression levels
      were influenced by NYHA class (p < 0.001). CONCLUSIONS: Our results suggest that
      there is a need to plan psychological support for these patients with
      consideration for the onset of cardiac symptoms and symptom severity.

PMID- 22624656
TI  - MetaDisorder: a meta-server for the prediction of intrinsic disorder in proteins.
AB  - BACKGROUND: Intrinsically unstructured proteins (IUPs) lack a well-defined three
      dimensional structure. Some of them may assume a locally stable structure under
      specific conditions, e.g. upon interaction with another molecule, while others
      function in a permanently unstructured state. The discovery of IUPs challenged
      the traditional protein structure paradigm, which stated that a specific well
      defined structure defines the function of the protein. As of December 2011,
      approximately 60 methods for computational prediction of protein disorder from
      sequence have been made publicly available. They are based on different
      approaches, such as utilizing evolutionary information, energy functions, and
      various statistical and machine learning methods. RESULTS: Given the diversity of
      existing intrinsic disorder prediction methods, we decided to test whether it is
      possible to combine them into a more accurate meta-prediction method. We
      developed a method based on arbitrarily chosen 13 disorder predictors, in which
      the final consensus was weighted by the accuracy of the methods. We have also
      developed a disorder predictor GSmetaDisorder3D that used no third-party disorder
      predictors, but alignments to known protein structures, reported by the protein
      fold-recognition methods, to infer the potentially structured and unstructured
      regions. Following the success of our disorder predictors in the CASP8 benchmark,
      we combined them into a meta-meta predictor called GSmetaDisorderMD, which was
      the top scoring method in the subsequent CASP9 benchmark. CONCLUSIONS: A series
      of disorder predictors described in this article is available as a MetaDisorder
      web server at http://iimcb.genesilico.pl/metadisorder/. Results are presented
      both in an easily interpretable, interactive mode and in a simple text format
      suitable for machine processing.

PMID- 22624657
TI  - Bacillus cereus septicemia attributed to a matched unrelated bone marrow
      transplant.
AB  - BACKGROUND: Hematopoietic cell transplantation (HCT) is performed in more than
      25,000 patients annually. Clinically significant bacterial transmission from HCT
      products is rare. CASE REPORT: A 36-year-old male of Asian descent with chronic
      myelogenous leukemia developed sepsis leading to acute renal failure and
      disseminated intravascular coagulation during infusion of matched unrelated donor
      bone marrow. This product later tested positive for Bacillus cereus. DISCUSSION:
      This HCT product traveled 31 hours at room temperature before arriving at the
      transplant center. Reducing transport times, transporting at 4  degrees C, and
      enhancing bacterial surveillance of HCT products may increase the ability to
      detect bacterial proliferation from transport. CONCLUSION: To prevent a similar
      case in the future, we will begin Gram staining all HCT products in transit more
      than 24 hours to alert physicians of the need for prophylactic antibiotic
      therapy.

PMID- 22624658
TI  - The impact of sample non-normality on ANOVA and alternative methods.
AB  - In this journal, Zimmerman (2004, 2011) has discussed preliminary tests that
      researchers often use to choose an appropriate method for comparing locations
      when the assumption of normality is doubtful. The conceptual problem with this
      approach is that such a two-stage process makes both the power and the
      significance of the entire procedure uncertain, as type I and type II errors are
      possible at both stages. A type I error at the first stage, for example, will
      obviously increase the probability of a type II error at the second stage. Based
      on the idea of Schmider et al. (2010), which proposes that simulated sets of
      sample data be ranked with respect to their degree of normality, this paper
      investigates the relationship between population non-normality and sample non
      normality with respect to the performance of the ANOVA, Brown-Forsythe test,
      Welch test, and Kruskal-Wallis test when used with different distributions,
      sample sizes, and effect sizes. The overall conclusion is that the Kruskal-Wallis
      test is considerably less sensitive to the degree of sample normality when
      populations are distinctly non-normal and should therefore be the primary tool
      used to compare locations when it is known that populations are not at least
      approximately normal.

PMID- 22624659
TI  - Exotic venomous snakebite drill.
AB  - BACKGROUND: There were 900 exotic venomous snakebites reported from 2000 to 2009.
      The Association of Zoos and Aquariums' recommends institutions housing venomous
      reptiles have protocols for appropriate and timely transport of envenomed
      individuals to hospitals. The study objective was to evaluate functional aspects
      and potential problems of our emergency operation procedure designed for handling
      the response to an exotic venomous snakebite during implementation via a
      simulated drill. The emergency operation procedure consists of two protocols, the
      protocol for zoo personnel and exotic snakebite protocol for hospital personnel.
      METHODS: Before the exercise the poison center (PC), zoo, Emergency Medical
      Services (EMS), receiving hospital emergency department (ED), and pharmacy were
      contacted. The emergency operation procedure was reviewed to determine areas of
      deficiency. A checklist of all required actions for each participating
      institution was created for use during the exercise. The exercise was divided
      into four phases: zoo, EMS, PC, and ED. Each phase was evaluated by an
      independent observer. RESULTS: Review of the emergency operation procedure
      revealed sufficient and easy to follow information for zoo personnel. However,
      the exotic snakebite protocol for hospital personnel lacked details regarding
      signs and symptoms expected from each exotic venomous species in the zoo; and
      indications, dosing, and instructions on reconstitution for each of the antivenom
      carried by the zoo. Zoo, EMS, ED, and PC personnel completed 95%, 90%, 83%, and
      25% of the required tasks, respectively. The PC encountered problems
      communicating the exotic snakebite protocol for hospital personnel to the ED due
      to phone and fax equipment failures. Creative solutions to the PC system issues
      were not identified in a timely manner. Despite the shortcomings, the time from
      simulated envenomation to antivenom (AV) administration was under an hour.
      CONCLUSIONS: This drill identified several issues leading to revision of our
      exotic snakebite protocol for hospital personnel. We also identified suboptimal
      PC response in the application of the emergency operation procedure. We encourage
      every poison center in cooperation with local zoos to perform a similar exercise.

PMID- 22624660
TI  - Factors associated with the decline in suicide by pesticide poisoning in Taiwan:
      a time trend analysis, 1987-2010.
AB  - OBJECTIVE: Pesticide self-poisoning accounts for one-third of suicides worldwide,
      but few studies have investigated the national epidemiology of pesticide suicide
      in countries where it is a commonly used method. We investigated trends in
      pesticide suicide, and factors associated with such trends, in Taiwan, a rapidly
      developing East Asian country. METHODS: We conducted an ecological study using
      graphical approaches and Spearman's correlation coefficients to examine trends in
      pesticide suicide (1987-2010) in Taiwan in relation to pesticide sales, bans on
      selected pesticides, the proportion of the workforce involved in agriculture and
      unemployment. We compared pesticide products banned by the Taiwanese government
      with products that remained on the market and pesticides that accounted for the
      most poisoning deaths in Taiwan. RESULTS: Age-standardised rates of pesticide
      suicide showed a 67% reduction from 7.7 per 100,000 (42% of all suicides) in 1987
      to 2.5 per 100,000 (12% of all suicides) in 2010, in contrast to a 69% increase
      in suicide rates by other methods. Pesticide poisoning was the most commonly used
      method of suicide in 1987 but had become the third most common method by 2010.
      The reduction was paralleled by a 66% fall in the workforce involved in
      agriculture but there was no strong evidence for its association with trends in
      pesticide sales, bans on selected pesticide products or unemployment. The bans
      mostly post-dated the decline in pesticide suicides; furthermore, they did not
      include products (e.g. paraquat) that accounted for most deaths and were mainly
      restricted to selected high-strength formulated products whilst their equivalent
      low-strength products were not banned. CONCLUSIONS: Access to pesticides,
      indicated by the size of agricultural workforce, appears to influence trends in
      pesticide suicide in Taiwan. Targeted bans on pesticides should focus on those
      products that account for most deaths.

PMID- 22624661
TI  - The impact of liver transplantation on family functioning in pediatric
      recipients: can "healthy" families contribute to improved long-term survival?

PMID- 22624662
TI  - Recognition of avirulence gene AvrLm1 from hemibiotrophic ascomycete
      Leptosphaeria maculans triggers salicylic acid and ethylene signaling in Brassica
      napus.
AB  - Interaction of a plant with a fungal pathogen is an encounter with hundreds of
      molecules. In contrast to this, a single molecule often decides between the
      disease and resistance. In the present article, we describe the defense responses
      triggered by AvrLm1, an avirulence gene from a hemibiotrophic ascomycete,
      Leptosphaeria maculans, responsible for an incompatible interaction with Brassica
      napus. Using multiple hormone quantification and expression analysis of defense
      related genes, we investigated signaling events in Rlm1 plants infected with two
      sister isolates of L. maculans differentiated by the presence or absence of
      AvrLm1. Infection with the isolate carrying AvrLm1 increased the biosynthesis of
      salicylic acid (SA) and induced expression of the SA-associated genes ICS1,
      WRKY70, and PR-1, a feature characteristic of responses to biotrophic pathogens
      and resistance gene-mediated resistance. In addition to SA-signaling elements, we
      also observed the induction of ASC2a, HEL, and CHI genes associated with ethylene
      (ET) signaling. Pharmacological experiments confirmed the positive roles of SA
      and ET in mediating resistance to L. maculans. The unusual cooperation of SA and
      ET signaling might be a response to the hemibiotrophic nature of L. maculans. Our
      results also demonstrate the profound difference between the natural host B.
      napus and the model plant Arabidopsis in their response to L. maculans infection.

PMID- 22624663
TI  - Is it useful to calculate sum scores of the quality of life questionnaire EORTC
      QLQ-C30?
AB  - The aim of this paper is to test the psychometric properties of sum scores of the
      quality of life questionnaire EORTC QLQ-C30. A sample of cancer patients (n=
      1529) and a sample of the general population (n= 1185) were tested with the EORTC
      QLQ-C30, the Hospital Anxiety and Depression Scale and the Multidimensional
      Fatigue Inventory. Three sum scores of the EORTC QLQ-C30 are defined: a score
      concerning functioning, a score concerning symptoms and a total score. Compared
      with the two-item quality of life scale of the EORTC QLQ-C30, the psychometric
      quality of the total score and the functioning score is superior with respect to
      reliability, convergent validity and discriminant validity. Cronbach's alpha of
      the total score is 0.94 (cancer patients) and 0.95 (general population). The
      effect size discriminating between patients and controls is d= 0.83 for the total
      score, compared to only 0.50 obtained with the two-item quality of life scale.
      The results prove that the calculation of sum scores provides useful information
      for clinicians who are interested in one generalising score of quality of life.

PMID- 22624664
TI  - Understanding the self-healing hydrophobic recovery of high-voltage insulators.
AB  - Amorphous siloxane polymers are designed to have high dielectric strength for use
      as high-voltage insulation materials. Surface hydrophobicity is essential and can
      be impaired by environmental, electrical, or mechanical factors, leading to
      leakage currents due to dielectric breakdown. Self-recovery is possible and is
      generally observed over a period of several hours. Using large-scale, all-atom
      molecular dynamics simulations, the surface wetting of water droplets on the
      polymer surface is simulated for various surface conditions, including oxidation
      and coating with small molecules, to understand the driving forces of the
      recovery process at the atomistic level, which is of primary importance for the
      developments of novel materials. In this work, we shed light onto the self
      recovery mechanism and propose the use of low-molecular-weight (LMW) siloxane to
      accelerate the recovery of hydrophobicity.

PMID- 22624665
TI  - Effects of climate and exurban development on nest predation and predator
      presence in the southern Appalachian Mountains (USA).
AB  - In the eastern United States, land-use and climate change have likely contributed
      to declines in the abundance of Neotropical migrant birds that occupy forest
      interiors, but the mechanisms are not well understood. We conducted a nest
      predation experiment in southern Appalachian Mountain forests (North Carolina,
      U.S.A.) during the 2009 and 2010 breeding seasons to determine the effects of
      exurban development and temperature on predator presence and the average number
      of days until eggs in an artificial nest were disturbed by predators. We baited
      artificial nests with quail (Excalfactoria chinensi) eggs and monitored them for
      18 days. We used clay eggs, track plates, and motion-triggered cameras to detect
      and identify nest predators. The average number of days a nest was undisturbed
      decreased as mean temperature increased and, to a lesser extent, as the density
      of buildings increased. Nests on the ground were more often depredated than those
      in trees, likely due to increased predation by opossum (Didelphis virginiana) and
      other carnivores. Raccoons (Procyon lotor), opossums, corvids (Corvus
      brachyrhynchos and Cyanocitta cristata), chipmunks (Tamias striatus), black bears
      (Ursus americanus), and domestic cats (Felis catus) were the most commonly
      detected predators. Presence of these predators did not vary as a function of
      mean temperature. Domestic cats and corvids were detected more frequently in
      plots with high rather than low densities of buildings. Forest-interior
      specialists and Neotropical migrants often nest in cool, high-elevation areas
      with low housing density. These bird species, especially those that nest on the
      ground, may be most vulnerable to increased nest predation if temperature and
      exurban development increase at higher elevations as anticipated.

PMID- 22624666
TI  - Multispectroscopic and molecular modeling approach to investigate the interaction
      of flavokawain B with human serum albumin.
AB  - Interaction of flavokawain B (FB), a multitherapeutic flavonoid from Alpinia
      mutica with the major transport protein, human serum albumin (HSA), was
      investigated using different spectroscopic probes, i.e., intrinsic, synchronous,
      and three-dimensional (3-D) fluorescence, circular dichroism (CD), and molecular
      modeling studies. Values of binding parameters for FB-HSA interaction in terms of
      binding constant and stoichiometry of binding were determined from the
      fluorescence quench titration and were found to be 6.88 * 10(4) M(-1) and 1.0 mol
      of FB bound per mole of protein, respectively, at 25  degrees C. Thermodynamic
      analysis of the binding data obtained at different temperatures showed that the
      binding process was primarily mediated by hydrophobic interactions and hydrogen
      bonding, as the values of the enthalpy change (DeltaH) and the entropy change
      (DeltaS) were found to be -6.87 kJ mol(-1) and 69.50 J mol(-1) K(-1),
      respectively. FB binding to HSA led to both secondary and tertiary structural
      alterations in the protein as revealed by intrinsic, synchronous, and 3-D
      fluorescence results. Increased thermal stability of HSA in the presence of FB
      was also evident from the far-UV CD spectral results. The distance between the
      bound ligand and Trp-214 of HSA was determined as 3.03 nm based on the Forster
      resonance energy transfer mechanism. Displacement experiments using bilirubin and
      warfarin coupled with molecular modeling studies assigned the binding site of FB
      on HSA at domain IIA, i.e., Sudlow's site I. 

PMID- 22624667
TI  - Men's susceptibility to HIV in Swaziland.
AB  - HIV prevention that uses gender as an analytical framework tends to focus on the
      ways in which gender inequalities differentially affect women's susceptibility to
      HIV infection. Men, in this context, are often conceptualized as aggressors, as
      opposed to women, who are seen as passive victims of HIV infection. In recent
      years, a growing number of researchers and public health officials have called
      attention to the pitfalls of this paradigm, pointing out that gender inequities
      harm both women and men. The first step towards transforming gender norms is to
      understand what norms currently exist. With this in mind, the aim of this paper
      is to consolidate and analyse literature that examines structural factors that
      contribute to the continued HIV infection of men in Swaziland, the country with
      the highest prevalence of HIV. Gaps in current literature related to this topic
      are also elucidated. Findings highlight the need for research to be conducted in
      Swaziland and elsewhere that investigates the effects of gender norms on the
      wellbeing of both women and men.

PMID- 22624668
TI  - In situ monitoring of protein adsorption on a nanoparticulated gold film by
      attenuated total reflection surface-enhanced infrared absorption spectroscopy.
AB  - In situ surface enhanced infrared absorption spectroscopy (SEIRAS) with an
      attenuated total reflection (ATR) configuration has been used to monitor the
      adsorption kinetics of bovine hemoglobin (BHb) on a Au nanoparticle (NP) film.
      The IR absorbance for BHb molecules on a gold nanoparticle film deposited on a Si
      hemispherical optical window is about 58 times higher than that on a bare Si
      optical window and the detection sensitivity has been improved by 3 orders of
      magnitude. From the IR signal as a function of adsorption time, the adsorption
      kinetics and thermodynamics can be explored in situ. It is found that both the
      electrostatic interaction and the coordination bonds between BHb residues and Au
      NP film surface affect the adsorption kinetics. The maximum adsorption can be
      obtained in solution pH 7.0 (close to the isoelectric point of the protein) due
      to the electrostatic interaction among proteins. In addition, the isotherm of BHb
      adsorption follows well the Freundlich adsorption model.

PMID- 22624669
TI  - Merging visible-light photocatalysis and transition-metal catalysis in the copper
      catalyzed trifluoromethylation of boronic acids with CF3I.
AB  - This communication describes the development of a mild method for the cross
      coupling of arylboronic acids with CF(3)I via the merger of photoredox and Cu
      catalysis. This method has been applied to the trifluoromethylation of
      electronically diverse aromatic and heteroaromatic substrates and tolerates many
      common functional groups.

PMID- 22624670
TI  - Exploring the spectrum of 3-M syndrome, a primordial short stature disorder of
      disrupted ubiquitination.
AB  - 3-M syndrome is an autosomal recessive primordial growth disorder characterized
      by small birth size and post-natal growth restriction associated with a spectrum
      of minor anomalies (including a triangular-shaped face, flat cheeks, full lips,
      short chest and prominent fleshy heels). Unlike many other primordial short
      stature syndromes, intelligence is normal and there is no other major system
      involvement, indicating that 3-M is predominantly a growth-related condition.
      From an endocrine perspective, serum GH levels are usually normal and IGF-I
      normal or low, while growth response to rhGH therapy is variable but typically
      poor. All these features suggest a degree of resistance in the GH-IGF axis. To
      date, mutations in three genes CUL7, OBSL1 and CCDC8 have been shown to cause 3
      M. CUL7 acts an ubiquitin ligase and is known to interact with p53, cyclin D-1
      and the growth factor signalling molecule IRS-1, the link with the latter may
      contribute to the GH-IGF resistance. OBSL1 is a putative cytoskeletal adaptor
      that interacts with and stabilizes CUL7. CCDC8 is the newest member of the
      pathway and interacts with OBSL1 and, like CUL7, associates with p53, acting as a
      co-factor in p53-medicated apoptosis. 3-M patients without a mutation have also
      been identified, indicating the involvement of additional genes in the pathway.
      Potentially damaging sequence variants in CUL7 and OBSL1 have been identified in
      idiopathic short stature (ISS), including those born small with failure of catch
      up growth, signifying that the 3-M pathway could play a wider role in disordered
      growth.

PMID- 22624671
TI  - Effect of 5-aza-2'-deoxycytidine on methylation of the putative imprinted control
      region of H19 during the in vitro development of vitrified bovine two-cell
      embryos.
AB  - OBJECTIVE: To determine the effect of vitrification and 5-aza-2'-deoxycytidine (5
      aza-dC) on the methylation levels of the putative imprinted control region (ICR)
      of H19 and H19 expression in bovine two-cell embryos and their derived
      blastocysts. DESIGN: Experimental animal study. SETTING: Academic institution.
      ANIMAL(S): Abattoir-derived bovine ovaries. INTERVENTION(S): Vitrified two-cell
      embryos were cultured in vitro to blastocysts with 0.01 MUM 5-aza-dC (5-aza-dC
      group) or without 5-aza-dC (vitrification group). Fresh embryos and their derived
      blastocysts were used as control. MAIN OUTCOME MEASURE(S): Putative ICR
      methylation of H19 was measured by bisulfate mutagenesis and sequencing,
      blastocyst development rate; total cell number were determined; and H19
      expression was measured by real-time reverse transcriptase-polymerase chain
      reaction (PCR). RESULT(S): Vitrification significantly increased putative ICR
      methylation of H19 in two-cell embryos and their derived blastocysts; 5-aza-dC
      significantly reduced putative ICR methylation of H19 in vitrified two-cell
      embryos and their derived blastocysts. The H19 expression level was significantly
      higher in blastocysts from the 5-aza-dC group than the vitrification group. The
      blastocyst development rate and total cell number in the 5-aza-dC and
      vitrification groups were similar. CONCLUSION(S): Putative ICR methylation levels
      of H19 significantly increased in vitrified two-cell embryos and their derived
      blastocysts; 5-aza-dC significantly reduced putative ICR methylation of H19 and
      increased H19 expression in blastocysts derived from vitrified two-cell embryos.

PMID- 22624673
TI  - Human sperm head vacuoles are physiological structures formed during the sperm
      development and maturation process.
AB  - OBJECTIVE: To clarify whether human sperm vacuoles affected intracytoplasmic
      sperm injection (ICSI) success rates. DESIGN: Retrospective study. SETTING: A
      private infertility clinic. PATIENT(S): Spermatozoa and spermatids were obtained
      from 11 normozoospermic, 10 oligozoospermic or asthenozoospermic, 4 obstructive
      azoospermic, and 3 nonobstructive azoospermic men. INTERVENTION(S): Differential
      interference contrast observation and intracytoplasmic injection of
      morphologically selected sperm. MAIN OUTCOME MEASURE(S): Incidence, size, and
      position of vacuoles of sperm cells were recorded. Ability of fertilization and
      blastocyst development were compared between cells with and without vacuoles.
      RESULT(S): More than 97.4% of ejaculated, 87.5% of epididymal, 87.5% of
      testicular spermatozoa, and more than 90.0% of Sc-Sd2 spermatids had vacuoles of
      various sizes. The incidence of vacuoles on ejaculated cells was significantly
      higher than that on the other types of cells, but there was no difference between
      sperm from normozoospermic men and those from the other donors. Removal of plasma
      membrane and/or acrosome did not affect the incidence of vacuoles. Although more
      than 60% of spermatozoa had small vacuoles in the acrosomal regions, 52.6% of Sb1
      2 spermatids had large vacuoles. After injection of a motile spermatozoon with
      large and small vacuoles, 60.9% and 85.7% of metaphase II oocytes could be
      normally fertilized, respectively, and almost half of the zygotes developed to
      the blastocyst stage. When using sperm without vacuoles, the fertilization rate
      was 80.0%, but only 25% of them developed to the blastocyst stage. CONCLUSION(S):
      Human sperm head vacuoles did not affect ICSI outcomes.

PMID- 22624672
TI  - Thyroid peroxidase antibody in women with unexplained recurrent miscarriage:
      prevalence, prognostic value, and response to empirical thyroxine therapy.
AB  - OBJECTIVE: To determine the prevalence, prognostic value, and response to
      thyroxine therapy of thyroid peroxidase antibody (TPOAb) in women with
      unexplained recurrent miscarriage (RM). DESIGN: Observational, cohort study. The
      index cases included women with unexplained RM who tested positive for thyroid
      peroxidase antibody, and control cases included women with unexplained RM who
      tested negative for the antibodies; a second age-matched control group included
      women with RM who had a known cause for the repeated pregnancy loss. SETTING:
      Tertiary referral center for RM. PATIENT(S): A total of 496 women with
      unexplained RM and 220 women with known diagnoses of RM who had a TPOAb test.
      INTERVENTION(S): Thyroxine replacement (50 MUg daily during pregnancy) was begun
      in some patients who tested positive for thyroid peroxidase antibody,
      irrespective of TSH level. MAIN OUTCOME MEASURE(S): Miscarriage and live birth
      rates of a subsequent pregnancy. RESULT(S): A total of 496 women with unexplained
      RM who had a TPOAb test were included in the study. Of these, 10.7% of subjects
      tested positive for TPOAb. The prevalence of TPOAb in control subjects who had a
      known cause for RM was 11.8%. The live birth rate of the first pregnancies after
      referral was 64%, 53%, and 58% in TPOAb-negative, TPOAb-positive with thyroxine
      treatment, and TPOAb-positive without treatment subjects; there was no
      significant difference in the outcome between any two or three groups, or between
      those who tested positive or negative for TPOAb. Among women who tested positive
      for TPOAb, there was no difference in the antibody titer between women with
      unexplained RM and those with a known cause for the pregnancy loss. Women who
      tested positive for TPOAb were significantly more likely to have TSH levels above
      the normal range (>=4.2 mIU/L). CONCLUSION(S): The prevalence of TPOAb-positive
      results in women with unexplained RM is not higher than in the general
      population, TPOAb-positive status does not have a prognostic value regarding the
      outcome of a subsequent pregnancy, and empirical thyroxine therapy in those who
      tested positive did not seem to improve outcome.

PMID- 22624674
TI  - Paternal and maternal carriage of the annexin A5 M2 haplotype are equal risk
      factors for recurrent pregnancy loss: a pilot study.
AB  - OBJECTIVE: To study the possible contribution of paternal, in addition to
      maternal, carriage of M2/ANXA5 as a risk factor for recurrent pregnancy loss
      (RPL). DESIGN: Case-control study. SETTING: Academic research center. PATIENT(S):
      Couples presenting themselves to the Fertility Center, Ludwig-Maximilians
      University Munich with two or more consecutive, unexplained miscarriages were
      selected for this study. Fertile female controls were from the same center and
      also from the resource of the Institute of Human Genetics, Westfalian Wilhelms
      University Muenster. Population controls were drafted from the PopGen biobank,
      University Clinic Schleswig-Holstein Kiel. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Incidence of M2 carriage was estimated in patient and control groups,
      odds ratios were calculated, and RPL risk was evaluated. RESULT(S): In comparison
      with female fertile controls, the risk for repeated abortion in the RPL group,
      associated with M2 carriage, was between 1.7 and 3.8, and it was 2.3 compared
      with population controls. Because of the equal genetic incidence of M2, with an
      allelic frequency of 0.167 in the female and male partner RPL subgroups, the
      haplotype confers approximately the same relative risk to carriers of both sexes.
      CONCLUSION(S): Paternal M2 carriage seems to confer an equal risk for recurrent
      miscarriages as M2 carriage in RPL mothers. This finding points to a role of
      ANXA5 and the M2 haplotype in the fetus and/or the extraembryonic membranes for
      pregnancy pathology. Prognostic RPL algorithms might be improved by testing the
      male partner for M2 carriage, and this may guide adequate therapeutic decisions.

PMID- 22624675
TI  - Genetic polymorphisms of molecules involved in host immune response to dengue
      virus infection.
AB  - The dengue virus (DENV) belongs to the flavivirus family. Each of the four
      distinct serotypes of this virus is capable of causing human disease, especially
      in tropical and subtropical areas. The majority of people infected with DENV
      manifest asymptomatic or dengue fever with flu-like self-limited symptoms.
      However, a small portion of patients emerge with severe manifestations referred
      to as dengue hemorrhagic fever, which has a high mortality rate if not treated
      promptly. The host immune system, which plays important roles throughout the
      whole process of DENV infection, has been confirmed to have double-edged effects
      on DENV infection. Recently, much attention has been paid to the genetic
      heterogeneity of molecules involved in the host immune response to DENV
      infection. This heterogeneity has been proved to be the determining factor for
      DENV disease orientation. The present review discusses the primary functions and
      single nucleotide polymorphisms of some critical molecules in the human DENV
      immunological defense, especially the polymorphism locus associated with the DENV
      pathogenesis and disease susceptibility.

PMID- 22624676
TI  - Long-term experience of patch graft failure after Ahmed Glaucoma Valve(r) surgery
      using donor dura and sclera allografts.
AB  - BACKGROUND AND OBJECTIVE: To report the long-term incidence, timing, and
      experience of patch graft failure (PGF) after Ahmed Glaucoma Valve (AGV) (New
      World Medical, Inc., Rancho Cucamonga, CA) surgery in a large consecutive case
      series using donor dura mater and sclera sequentially as the allograft materials.
      PATIENTS AND METHODS: The medical records of all AGV surgeries performed from
      June 1994 through December 2010 were retrospectively reviewed for cases of PGF.
      RESULTS: Patch graft failure occurred in 44 (6.3%) of the initial 695 procedures
      using dura and in 65 (5.8%) of the subsequent 1,121 procedures using sclera (P =
      .64). The time interval after AGV surgery until the occurrence of PGF was
      significantly longer for dura (5.8 +/- 3.8 years) than for sclera (2.7 +/- 1.9
      years) (P < .001). CONCLUSION: After an average of 4 years, PGF occurred in 109
      (6%) of 1,816 consecutive AGV surgeries using donor dura and sclera allografts.
      PGF may be the most frequent long-term complication after AGV surgery.

PMID- 22624677
TI  - An instrument assessing patient satisfaction with day care in hospitals.
AB  - BACKGROUND: Patient satisfaction is an important indicator of quality of care in
      hospitals. Reliable and valid instruments to measure clinical and outpatient
      satisfaction already exist. Recently hospitals have increasingly provided day
      care, i.e., admitting patients for one day without an overnight stay. This
      article describes the adaption of the 'Core questionnaire for the assessment of
      Patient Satisfaction' (COPS) for general Day care (COPS-D), and the subsequent
      validation of the COPS-D. METHODS: The clinical COPS was supplemented with items
      to cover two new dimensions: Pre-admission visit and Operation Room. It was sent
      to a sample of day care patients of five general Dutch hospitals to investigate
      dimensionality, acceptability, reliability, construct and external validity.
      Construct validity was established by correlating the dimensions of the COPS-D
      with patients' overall satisfaction. RESULTS: The COPS-D was returned by 3802
      patients (response 46%). Factor analysis confirmed its' structure: Pre-intake
      visit, Admission, Operation room, Nursing care, Medical care, Information,
      Autonomy and Discharge and aftercare (extraction communality 0.63-0.90). The
      internal consistency of the eight dimensions was good (alpha = 0.82-0.90); the
      item internal consistency corrected for overlap was satisfactory (>0.40); all
      inter-item correlations were higher than 0.45 but not too high (<0.90). The
      construct validity of all dimensions was good (r from 0.52-0.62, p < 0.01). The
      Information dimension had the strongest correlation with overall day care
      satisfaction. CONCLUSIONS: The COPS-D is a reliable and valid instrument for
      measuring satisfaction with day care. It complements the model of measuring
      patient satisfaction with clinical and outpatient care given in hospitals. It
      also fulfils the conditions made while developing the clinical and outpatient
      COPS: a short, core instrument to screen patient satisfaction.

PMID- 22624678
TI  - Single copy nuclear gene analysis of polyploidy in wild potatoes (Solanum section
      Petota).
AB  - BACKGROUND: Recent genomic studies have drastically altered our knowledge of
      polyploid evolution. Wild potatoes (Solanum section Petota) are a highly diverse
      and economically important group of about 100 species widely distributed
      throughout the Americas. Thirty-six percent of the species in section Petota are
      polyploid or with diploid and polyploid cytotypes. However, the group is poorly
      understood at the genomic level and the series is ideal to study polyploid
      evolution. Two separate studies using the nuclear orthologs GBSSI and nitrate
      reductase confirmed prior hypotheses of polyploid origins in potato and have
      shown new origins not proposed before. These studies have been limited, however,
      by the use of few accessions per polyploid species and by low taxonomic
      resolution, providing clade-specific, but not species-specific origins within
      clades. The purpose of the present study is to use six nuclear orthologs, within
      54 accessions of 11 polyploid species, 34 accessions of 29 diploid species of
      section Petota representing their putative progenitors, and two outgroups, to see
      if phenomena typical of other polyploid groups occur within wild potatoes, to
      include multiple origins, loss of alleles, or gain of new alleles. RESULTS: Our
      results increase resolution within clades, giving better ideas of diploid
      progenitors, and show unexpected complexity of allele sharing within clades.
      While some species have little diversity among accessions and concur with the
      GBSSI and nitrate reductase results, such as S. agrimonifolium, S. colombianum,
      S. hjertingii, and S. moscopanum, the results give much better resolution of
      species-specific progenitors. Seven other species, however, show variant patterns
      of allele distributions suggesting multiple origins and allele loss. Complex
      three-genome origins are supported for S. hougasii, and S. schenckii, and one of
      the ten accessions of S. stoloniferum. A very unexpected shared presence of
      alleles occurs within one clade of S. verrucosum from Central America, and S.
      berthaultii from South America in six polyploid species S. demissum, S.
      hjertingii, S. hougasii, S. iopetalum, S. schenckii, and S. stoloniferum.
      CONCLUSIONS: Our results document considerable genomic complexity of some wild
      potato polyploids. These can be explained by multiple hybrid origins and allele
      losses that provide a clear biological explanation for the taxonomic complexity
      in wild potato polyploids. These results are of theoretical and practical benefit
      to potato breeders, and add to a growing body of evidence showing considerable
      complexity in polyploid plants in general.

PMID- 22624679
TI  - Relationship between physical activity, physical performance, and iron status in
      adult women.
AB  - Iron deficiency affects approximately 16% of US females 18-45 years old. Iron is
      a key component of heme-containing proteins, which are essential for oxygen
      transport throughout the body. With low iron levels, performance and intense
      physical activity may be compromised. Thus, the purpose of this study was to
      examine the relationship between iron status, physical performance, and physical
      activity in 18- to 45-year-old females. Participants (N = 109) were screened for
      iron status using a venous blood sample, had their height and mass measured, and
      self-reported their physical activity level. The screening was used to match iron
      depleted nonanemic females (hemoglobin, Hgb > 120 g.L(-1); serum ferritin, sFer <
      20 ug.L(-1)) to females with normal iron levels. After participant matching, they
      had their body composition measured, performed three cycle ergometer tests
      (maximal, endurance, and efficiency), and wore an ActiGraph GT1M accelerometer
      for five consecutive days, except when sleeping or during water activities. The
      final sample consisted of 25 iron-depleted participants and 24 with normal iron
      levels. Key findings were as follows: (i) after controlling for fat-free mass and
      vigorous physical activity, iron-depleted females had a significantly lower
      [Formula: see text]O(2) at ventilatory threshold compared with those with normal
      iron levels (P < 0.05); and (ii) after controlling for age, iron-depleted females
      spent significantly more time in sedentary behaviors and significantly less time
      in light physical activity than those with normal iron levels (P < 0.05). The
      increased sedentary time in iron-depleted females may contribute to excess mass
      gain over time; however, further investigation is needed to confirm these
      results.

PMID- 22624680
TI  - Inhibition of human recombinant T-type calcium channels by N-arachidonoyl 5-HT.
AB  - BACKGROUND AND PURPOSE: N-arachidonoyl 5-HT (NA-5HT) has anti-nociceptive effects
      reported to be mediated by inhibitory actions at the transient receptor potential
      vanilloid receptor 1 (TRPV1) and fatty acid amide hydrolase (FAAH). Anandamide
      and N-arachidonoyl dopamine (NA-DA), endocannabinoids that activate TRPV1 or are
      metabolized by FAAH, also inhibit T-type calcium channels (I(Ca) ). T-type I(Ca)
      are expressed by many excitable cells, including neurons involved in pain
      detection and processing. We sought to determine whether NA-5HT also modulates T
      type I(Ca) . EXPERIMENTAL APPROACH: Human recombinant T-type I(Ca) (Ca(V) 3
      channels) expressed in HEK 293 cells were examined using standard whole-cell
      voltage-clamp electrophysiology techniques. KEY RESULTS: NA-5HT completely
      inhibited Ca(V) 3 channels with a rank order of potency (pEC(50) ) of Ca(V) 3.1
      (7.4) > Ca(V) 3.3 (6.8) >= Ca(V) 3.2 (6.6). The effects of NA-5HT were voltage
      dependent, and it produced significant hyperpolarizing shifts in Ca(V) 3 steady
      state inactivation relationships. NA-5HT selectively affected Ca(V) 3.3 channel
      kinetics. CONCLUSIONS AND IMPLICATIONS: NA-5HT increases the steady-state
      inactivation of Ca(V) 3 channels, reducing the number of channels available to
      open during depolarization. These effects occur at NA-5HT concentrations at or
      below those at which NA-5HT affects TRPV1 receptors and FAAH. NA-5HT is one of
      the most potent inhibitors of T-type I(Ca) described to date, and it is likely to
      exert some of its biological effects, including anti-nociception, via inhibition
      of these channels.

PMID- 22624681
TI  - Identification of systemic responses in soybean nodulation by xylem sap feeding
      and complete transcriptome sequencing reveal a novel component of the
      autoregulation pathway.
AB  - Establishment of the nitrogen-fixing nodulation symbiosis between legumes and
      rhizobia requires plant-wide reprogramming to allow infection and development of
      nodules. Nodulation is regulated principally via a mechanism called
      autoregulation of nodulation (AON). AON is dependent on shoot and root factors
      and is maintained by the nodulation autoregulation receptor kinase (NARK) in
      soybean. We developed a bioassay to detect root-derived signalling molecules in
      xylem sap of soybean plants which may function in AON. The bioassay involves
      feeding of xylem extracts via the cut hypocotyl of soybean seedlings and
      monitoring of molecular markers of AON in the leaf. Transcript abundance changes
      occurring in the leaf in response to feeding were used to determine the
      biological activity of the extracts. To identify transcript abundance changes
      that occur during AON, which may also be used in the bioassay, we used an RNA-seq
      based transcriptomics approach. We identified changes in the leaves of bioassay
      plants fed with xylem extracts derived from either Bradyrhizobium japonicum
      inoculated or uninoculated plants. Differential expression responses were
      detected for genes involved in jasmonic acid metabolism, pathogenesis and
      receptor kinase signalling. We identified an inoculation- and NARK-dependent
      candidate gene (GmUFD1a) that responds in both the bioassay and intact,
      inoculated plants. GmUFD1a is a component of the ubiquitin-dependent protein
      degradation pathway and provides new insight into the molecular responses
      occurring during AON. It may now also be used in our feeding bioassay as a
      molecular marker to assist in identifying the factors contributing to the
      systemic regulation of nodulation.

PMID- 22624682
TI  - Body mass index and postoperative complications in kidney transplant recipients.
AB  - BACKGROUND: There is a growing number of overweight and obese patients receiving
      kidney transplants, despite elevated body mass index (BMI) being associated with
      postoperative complications. Understanding associations between BMI and
      complications would allow more objectivity when recommending patients for
      transplantation or otherwise. METHODS: We analysed a retrospective cohort of 508
      adult patients who received primary kidney grafts at a single centre in South
      Australia, 2002-2009, using hospital records and Australia and New Zealand
      Dialysis and Transplant Registry (ANZDATA) data. Complications within 1 year of
      transplantation were classified into: surgical, wound, urological, delayed graft
      function, early nephrectomy and admission to intensive care unit (ICU). RESULTS:
      Overall, 62% of transplant recipients had a BMI above 25 kg/m(2) at transplant.
      Higher BMI was associated with an increased risk of wound complications (P <
      0.001), early nephrectomy (P = 0.002) and delayed graft function (P = 0.03), but
      not associated with surgical or urological complications, or ICU admission. These
      associations were stronger for Indigenous Australians than other patients,
      especially for surgical complications. There was no BMI value above which risks
      of complications increase substantially. CONCLUSION:   Delayed graft function is
      an important determinant of patient outcomes. Wound complications can be serious,
      and are more common in patients with higher BMI. This may justify the use of
      elevated BMI as a contraindication for transplantation, although no obvious cut
      off value exists. Investigations into other measures of body fat composition and
      distribution are warranted.

PMID- 22624683
TI  - Can you trust a computer to read your electrocardiogram?

PMID- 22624684
TI  - Review: Management of postprandial diarrhea syndrome.
AB  - Unexpected, urgent, sometimes painful bowel movements after eating are common
      complaints among adults. Without a clear etiology, if pain is present and
      resolves with the movements, this is usually labeled "irritable bowel syndrome
      diarrhea" based solely on symptoms. If this symptom-based approach is applied
      exclusively, it may lead physicians not to consider treatable conditions: celiac
      disease, or maldigestion due to bile acid malabsorption, pancreatic exocrine
      insufficiency, or an a-glucosidase (sucrase, glucoamylase, maltase, or
      isomaltase) deficiency. These conditions can be misdiagnosed as irritable bowel
      syndrome-diarrhea (or functional diarrhea, if pain is not present). Limited
      testing is currently available to confirm these conditions (antibody screens for
      celiac disease; fecal fat as a surrogate marker for pancreatic function).
      Therefore, empirical treatment with alpha amylase, pancreatic enzymes, or a bile
      acid-binding agent may simultaneously treat these patients and serve as a
      surrogate diagnostic test. This review will summarize the current evidence for
      bile acid malabsorption, and deficiencies of pancreatic enzymes or a-glucosidases
      as potential causes for postprandial diarrhea, and provide an algorithm for
      treatment options.

PMID- 22624685
TI  - Outcomes from a medical weight loss program: primary care clinics versus weight
      loss clinics.
AB  - BACKGROUND: Few studies have focused on weight loss programs implemented in
      community-based primary care settings. The objective of this analysis was to
      evaluate the effectiveness of a weight loss program and determine whether
      physicians in primary care practices could achieve reductions in body weight and
      body fat similar to those obtained in weight loss clinics. METHODS: Analyses were
      performed on chart review data from 413 obese participants who underwent weight
      loss at a primary care (n=234) or weight loss (n=179) clinic. Participants
      received physician-guided behavioral modification sessions and self-selected a
      diet plan partially or fully supplemented by meal replacements. A repeated
      measures analysis of covariance was conducted with age and sex serving as
      covariates; significance was set at P<=.05. RESULTS: In 178 subjects (43%)
      completing 12 weeks of the program, primary care clinics were as effective as
      weight loss clinics at achieving reductions in body weight (12.4 vs 12.1 kg) but
      better with regard to reduction in body fat percentage (3.8% vs 2.7%; P<=.05).
      Regardless of location, participants completing 12 weeks lost an average of 11.1%
      of their body weight. Participants selecting full meal replacement had greater
      reductions in weight and body fat percentage (12.7 kg, 3.5%) compared with
      participants selecting a partial meal replacement plan (8.3 kg, 2.3%).
      CONCLUSION: Primary care physicians can successfully manage and treat obese
      patients using behavioral modification techniques coupled with meal replacement
      diets.

PMID- 22624686
TI  - Inpatient outcomes and physician years in practice.

PMID- 22624688
TI  - Role of sodium bicarbonate in the treatment of methanol-induced acidosis.

PMID- 22624689
TI  - A reappraisal of chlorthalidone also is required.

PMID- 22624691
TI  - Can selection bias in trials allow hydrochlorothiazide to be banned?

PMID- 22624693
TI  - Gastric perforation after Heimlich maneuver.

PMID- 22624694
TI  - Comprehensive chronic pain management: improving physical and psychological
      function (CME multimedia activity).
AB  - As shown in this CME online activity (www.cmeaccess.com/AJM/ChronicPain02),
      chronic, non-cancer pain can arise from a variety of etiologies and can be
      broadly classified based on its underlying mechanism as nociceptive,
      inflammatory, neuropathic, or central, with some patients having pain arising
      from a combination of mechanisms. Chronic pain assessment and treatment involves
      evaluating not only its biological aspects, but also psychological and
      sociocultural factors. Beyond neural mechanisms, a patient's perception of
      chronic pain can be influenced by comorbid mood disorders, such as depression and
      anxiety; cognitive and affective traits, such as catastrophizing and fear
      avoidance; environmental stressors, family relationships, social support, and
      cultural beliefs. Based on this biopsychosocial model, a multidisciplinary
      approach to management incorporates pharmacotherapy (opioid, nonopioid, and
      centrally-acting analgesics, and pain adjuvant medications) with nonpharmacologic
      physical rehabilitation and psychological and behavioral therapies to address the
      multifactorial causes of chronic pain, which in turn leads to improvement of
      physical and psychological function.

PMID- 22624695
TI  - Hepatitis B prophylaxis post liver transplantation with newer nucleos(t)ide
      analogues after hepatitis B immunoglobulin discontinuation.
AB  - Newer nucleos(t)ide analogues (NUCs) have better resistance profiles making
      hepatitis B immunoglobulin (HBIG)-sparing protocol an attractive prophylactic
      approach against hepatitis B virus (HBV) recurrence after liver transplantation
      (LT). We evaluated the risk of HBV recurrence after withdrawal of HBIG in
      patients who had been under HBIG plus NUCs after LT. Stable patients without HBV
      recurrence after LT while receiving combination of HBIG plus NUCs for at least 12
      months were eligible for HBIG discontinuation. The patients were at low risk for
      HBV recurrence (only 4.5% had detectable HBV DNA at the time of LT, and 32% had
      HBV/hepatitis D virus co-infection). All patients were followed up with HBV serum
      markers, HBV-DNA, and evaluation of renal function, including glomerular
      filtration rate. Forty-seven recipients discontinued HBIG and were maintained on
      newer NUCs. Median follow-up post-HBIG withdrawal was 24 months (range: 6-40
      months). Twenty-eight (60%) patients continued on lamivudine in combination with
      adefovir dipivoxil (n = 23, 82%) or tenofovir (n = 5, 18%); 10 (21%) and 9 (19%)
      of the 47 patients continued on tenofovir and entecavir monoprophylaxis,
      respectively. Although 3 (6.3%) patients developed detectable hepatitis B surface
      antigen, all of them had undetectable HBV DNA and no clinical manifestations of
      HBV recurrence. Renal function was similar between the different groups of
      patients. In conclusion, maintenance therapy with newer NUCs after
      discontinuation of HBIG prophylaxis was effective, but further studies in larger
      cohorts with longer follow-up are needed.

PMID- 22624696
TI  - Comparative analysis of the pathological events involved in immune and non-immune
      TRALI models.
AB  - BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is
      characterized by leukocyte transmigration and alveolar capillary leakage shortly
      after transfusion. TRALI pathogenesis has not been fully elucidated. In some
      cases, the infusion of alloantibodies (immune model), whereas in others the
      combination of neutrophil priming by proinflammatory molecules with the
      subsequent infusion of biological response modifiers (BRMs) in the hemocomponent
      (non-immune model) have been implicated. Our aim was to compare the pathological
      events involved in TRALI induced by antibodies or BRMs using murine models.
      MATERIALS AND METHODS: In the immune model, human HNA-2(+) neutrophils were
      incubated in vitro with a monoclonal antibody (anti-CD177, clone 7D8) directed
      against the HNA-2 antigen and injected i.v. in NOD/SCID mice. In the non-immune
      model, BALB/c mice were treated with low doses of lipopolysaccharide (LPS)
      followed by platelet-activating factor (PAF) infusion 2 h later. Forty minutes
      after PAF administration, or 6 h after neutrophil injection, lungs were isolated
      and histological analysis, determination of a variety of cytokines and chemokines
      including keratinocyte-derived chemokine (KC), MIP-2, the interleukins IL-1beta,
      IL-6, IL-8 as well as TNFalpha, cell influx and alveolar capillary leakage were
      performed. RESULTS: In both models, characteristic histological findings of TRALI
      and an increase in KC and MIP-2 levels were detected. In contrast to the immune
      model, in the non-immune model, there was a dramatic increase in IL-1beta and
      TNFalpha. However, capillary leakage was only detected if PAF was administrated.
      CONCLUSIONS: Regardless of the triggering event(s), KC, MIP-2 and integrins
      participate in TRALI pathogenesis, whereas PAF is essential for capillary leakage
      when two events are involved.

PMID- 22624698
TI  - Is volume the only factor that impacts cord blood processing efficiency?

PMID- 22624697
TI  - Analgesia effect of a fixed nitrous oxide/oxygen mixture on burn dressing pain:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Procedural burn pain is the most intense acute pain and most likely
      type of burn injury pain to be undertreated due to the physician's fear of the
      adverse effect of analgesia and lack of anesthetist present. At our institution,
      in most of the cases, local burn detersion and debridement were performed at the
      ward level without any analgesics. This article describes a study designed to
      test the analgesia effect of a fixed nitrous oxide/oxygen mixture on burn
      dressing pain. METHODS/DESIGN: The experiment was carried out in three centers.
      The patients were given a number from 1 to 240. A randomization list was produced
      by a statistician according to our preliminary study. Due to the severity of the
      pain suffered, ethically it was decided to help as many as possible, so patients
      given the letters A, B or C were treated using a canister with the appropriate
      letter containing preprepared nitrous oxide/oxygen mixture (NOOM). Those with D
      were given oxygen only, from an identical-looking canister labeled D. Neither
      patients, nor doctors, nor nurses, nor data collector knew what was in each
      canister, thus they were all blind. The nursing officer who implemented the
      intervention handed the doctors envelopes containing the patients' name and
      allocation of A, B, C or D. Thus, patients receiving NOOM or oxygen were in the
      ratio 3:1. Parameters, including pain severity, blood pressure, heart rate,
      digital oxygen saturation and the Chinese version of the burn specific pain
      anxiety scale (C-BSPAS), were taken before, during and after dressing for each
      group. A video and audio record was taken individually for later communication
      coding and outcome analysis. Rescue analgesic was recorded. DISCUSSION: Based on
      the findings from our previous qualitative study that physician's reluctance to
      order narcotic analgesia is due to its adverse effect and from our pilot
      experiment, this study aims to test the hypothesis that a fixed nitrous
      oxide/oxygen mixture will promote better burn dressing pain alleviation and
      outcomes. Analyses will focus on the effects of the experimental intervention on
      pain severity during dressing (primary outcomes); physiological parameters, C
      BSPAS and acceptance of both health care professionals and patients (secondary
      outcomes). If this model of analgesia for burn pain management implemented by
      nurses proves successful, it could potentially be implemented widely in hospital
      and prehospital settings and improve patients' satisfaction and quality of life.
      TRIAL REGISTRATION: (Clinical Trials Identifier: CHICTR-TRC11001690).

PMID- 22624699
TI  - Cardiac pressure overload initiates a systemic stem cell response.
AB  - BACKGROUND AIMS: Acute cardiac injury results in the activation and recruitment
      of resident and non-cardiac stem cells. In this study we sought to define the
      pattern of peripheral stem cells and resident cardiac stem cell (CSC) activation
      induced acutely by cardiac pressure overload (PO). METHODS: PO was induced in
      mice by transaortic constriction (TAC). CSC, endothelial progenitor cells (EPC),
      hematopoietic stem cells (HSC) and stage-specific embryonic antigen (SSEA)-1(+)
      cells were profiled in the heart, spleen and bone marrow after TAC by flow
      cytometry. RESULTS: The combination of a systemic and local stem cell response
      resulted in increases in SSEA-1 (+) cells and EPC in the heart 7 and 14 days post
      TAC, respectively. Locally, modest SSEA-1(+) proliferation at 4 days preceded the
      elevated myocardial stem cell number. We observed no significant proliferation of
      EPC and CSC in the heart. The systemic stem cell response was characterized by a
      biphasic loss of splenic SSEA-1(+) cells at 2 and 7 days post-TAC and loss of
      bone marrow and spleen EPC at 4 and 7 days, respectively. Spleen size changed
      dynamically after TAC. A negligible response of HSC to TAC was observed.
      Significant EPC and SSEA-1(+) proliferation in the bone marrow and spleen
      occurred only after their local levels were decreased. CONCLUSIONS: Our results
      demonstrate that an orchestrated systemic stem cell response (EPC and SSEA-1 (+)
      ) takes place in response to TAC. The increase of SSEA-1(+) cells and EPC in the
      heart in response to pressure is likely to be because of a combination of local
      proliferation and stem cell recruitment.

PMID- 22624700
TI  - Isoelectric solubilization/precipitation as a means to recover protein isolate
      from striped bass (Morone saxatilis) and its physicochemical properties in a
      nutraceutical seafood product.
AB  - Excessive dietary intake of Na (i.e., NaCl) contributes to hypertension, which is
      a major risk factor for cardiovascular disease. Normally, NaOH and HCl are used
      to dissolve and precipitate, respectively, fish muscle proteins in isoelectric
      solubilization/precipitation (ISP), therefore contributing to increased Na
      content in the recovered fish protein isolates (FPI). Substitution of NaOH with
      KOH may decrease the Na content in FPI and, thus, allow development of reduced-Na
      seafood products. In this study, FPI was recovered with ISP using NaOH or KOH. In
      order to develop a nutraceutical seafood product, the FPI was extracted with NaCl
      or KCl-based salt substitute and subjected to cold- or heat-gelation. In
      addition, standard nutraceutical additives (omega-3 fatty acids-rich oil and
      dietary fiber) along with titanium dioxide (TiO2) were added to FPI. Color,
      texture, dynamic rheology, Na and K content, and lipid oxidation of the FPI gels
      were compared to commercial Alaska pollock surimi gels. FPI gels had greater (p <
      0.05) whiteness, good color properties (L*a*b*), and generally better textural
      properties when compared to surimi gels. Although the ISP-recovered FPI and
      surimi developed similar final gel elasticity, the proteins in FPI and surimi had
      different gelation pattern. A reduction (p < 0.05) of Na content and simultaneous
      increase (p < 0.05) in K content of FPI gels was achieved by the substitution of
      NaOH with KOH during ISP and NaCl with the KCl-based salt substitute during
      formulation of the FPI paste. Although cooking and addition of NaCl during
      formulation of the FPI paste increased (p < 0.05) lipid oxidation in FPI gels,
      TBARS values were much below rancidity levels. These results indicate that KOH
      can replace NaOH to recover FPI from whole gutted fish for subsequent development
      of nutraceutical seafood products tailored for reduction of diet-driven
      cardiovascular disease. 

PMID- 22624701
TI  - Development and testing of an instrument to assess nurses' knowledge, risk
      perception, health beliefs and behaviours related to influenza vaccination.
AB  - AIMS AND OBJECTIVES: To develop an instrument to measure nurses' knowledge, risk
      perception and health beliefs towards influenza and influenza vaccination and
      their vaccination behaviours and evaluate its construct validity and internal
      consistency reliability. BACKGROUND: Although instruments to assess predictors of
      nurses' vaccination behaviours have been developed, their validity and
      reliability have not been reported. DESIGN: Instrument development and initial
      validity and reliability testing. METHODS: The instrument was developed drawing
      on a literature review and expert consultation and was refined through pilot
      work. A cross-sectional survey using a revised version of the instrument was
      conducted among a convenience sample of 520 registered nurses (response rate
      77.4%). Cronbach's alpha coefficient was calculated to determine internal
      consistency of the sub-scale in the instrument. Principal components analysis
      with varimax rotation was carried out to evaluate the instrument's construct
      validity and examine its internal structure. RESULTS: Cronbach's alpha
      coefficients for the three newly developed scales ranged from 0.70-0.76.
      Principal components analysis produced a good fit and confirmed the internal
      design of the instrument. In the seasonal influenza knowledge sub-scale four
      factors explained 44.8% of the total variance; in the H1N1 knowledge sub-scale
      two factors explained 44.7% of the total variance. Three factors in the risk
      perception scale contributed 50.5% of the total variance and two factors in the
      vaccination behaviours scale contributed 62.1% of the total variance.
      CONCLUSIONS: An instrument has been developed to assess nurses' knowledge, risk
      perception and health beliefs towards influenza and influenza vaccination and
      their vaccination behaviours. The instrument was valid and reliable for the
      setting where it was used. RELEVANCE TO CLINICAL PRACTICE: This instrument could
      be used to assess nurses' knowledge, risk perception, health beliefs towards
      influenza and influenza vaccination and their vaccination behaviours. The three
      newly developed scales could also be used independently to measure variables
      influencing nurses' vaccination practices.

PMID- 22624702
TI  - Population dynamics of Hawaiian seabird colonies vulnerable to sea-level rise.
AB  - Globally, seabirds are vulnerable to anthropogenic threats both at sea and on
      land. Seabirds typically nest colonially and show strong fidelity to natal
      colonies, and such colonies on low-lying islands may be threatened by sea-level
      rise. We used French Frigate Shoals, the largest atoll in the Hawaiian
      Archipelago, as a case study to explore the population dynamics of seabird
      colonies and the potential effects sea-level rise may have on these rookeries. We
      compiled historic observations, a 30-year time series of seabird population
      abundance, lidar-derived elevations, and aerial imagery of all the islands of
      French Frigate Shoals. To estimate the population dynamics of 8 species of
      breeding seabirds on Tern Island from 1980 to 2009, we used a Gompertz model with
      a Bayesian approach to infer population growth rates, density dependence, process
      variation, and observation error. All species increased in abundance, in a
      pattern that provided evidence of density dependence. Great Frigatebirds (Fregata
      minor), Masked Boobies (Sula dactylatra), Red-tailed Tropicbirds (Phaethon
      rubricauda), Spectacled Terns (Onychoprion lunatus), and White Terns (Gygis alba)
      are likely at carrying capacity. Density dependence may exacerbate the effects of
      sea-level rise on seabirds because populations near carrying capacity on an
      island will be more negatively affected than populations with room for growth. We
      projected 12% of French Frigate Shoals will be inundated if sea level rises 1 m
      and 28% if sea level rises 2 m. Spectacled Terns and shrub-nesting species are
      especially vulnerable to sea-level rise, but seawalls and habitat restoration may
      mitigate the effects of sea-level rise. Losses of seabird nesting habitat may be
      substantial in the Hawaiian Islands by 2100 if sea levels rise 2 m. Restoration
      of higher-elevation seabird colonies represent a more enduring conservation
      solution for Pacific seabirds.

PMID- 22624703
TI  - How many chiral centers can Raman optical activity spectroscopy distinguish in a
      molecule?
AB  - To study the capabilities and limitations of Raman optical activity, (-)-(M)sigma
      [10]helicene and (-)-(M)sigma-[4]helicene serve as scaffold molecules on which
      new chiral centers are introduced by substitution of hydrogen atoms with other
      functional groups. These functional groups are deuterium atoms, fluorine atoms,
      and methyl groups. Multiply deuterated species are compared. Then, results of
      singly deuterated derivatives are compared against results obtained from singly
      fluorinated and methylated derivatives. The analysis required the calculation of
      a total of 2433 Raman optical activity spectra. The method we propose for the
      comparison of the various Raman optical activity spectra is based on the total
      intensity of squared difference spectra. This allows a qualitative comparison of
      pairs of Raman optical activity spectra and the extraction of the pair of most
      similar Raman optical activity spectra for each group of stereoisomers. Different
      factors were accounted for, such as the spectral resolution (modeled by line
      broadening) and the range of vibrational frequencies considered. In the case of
      sigma-[4]helicene all generated stereoisomers in each group can be distinguished
      from one another by Raman optical activity spectroscopy. For sigma-[10]helicene
      this holds except for the lower one of the two resolutions considered. Here, the
      group consisting of stereoisomers with five chiral centers contains at least one
      pair of derivatives whose Raman optical activity spectra cannot be distinguished
      from one another. This indicates that an increased molecular size has a negative
      effect on the number of chiral centers which can be distinguished by Raman
      optical activity spectroscopy. Regarding the different substituents, 
      stereoisomers are the better distinguishable in Raman optical activity
      spectroscopy, the more distinct the signals of the substituent are from the rest
      of the spectrum.

PMID- 22624704
TI  - Bifunctional Janus microparticles with spatially segregated proteins.
AB  - We present a fabrication process to create bifunctional microparticles displaying
      two distinct proteins that are spatially segregated onto the surface hemispheres.
      Silica and polystyrene microparticles with 2.0, 4.1, and 4.7 MUm diameters are
      processed with metal deposition to form two chemically distinct and segregated
      hemispheres. The surface of each hemisphere is then separately derivatized with
      biological proteins using different chemical conjugation strategies. These
      bifunctional Janus particles possess biologically relevant, native conformation
      proteins attached to a biologically unreactive and safe substrate. They also
      display high densities of each type of protein which may enable a range of
      capabilities that monofunctional particles cannot, such as improved targeting of
      drugs and bioimaging agents.

PMID- 22624705
TI  - The effects of distraction and a brief intervention on auditory and visual
      spatial working memory in college students with attention deficit hyperactivity
      disorder.
AB  - Two studies addressed how young adult college students with attention deficit
      hyperactivity disorder (ADHD) (n = 44) compare to their nonaffected peers (n =
      42) on tests of auditory and visual-spatial working memory (WM), are vulnerable
      to auditory and visual distractions, and are affected by a simple intervention.
      Students with ADHD demonstrated worse auditory WM than did controls. A near
      significant trend indicated that auditory distractions interfered with the visual
      WM of both groups and that, whereas controls were also vulnerable to visual
      distractions, visual distractions improved visual WM in the ADHD group. The
      intervention was ineffective. Limited correlations emerged between self-reported
      ADHD symptoms and objective test performances; students with ADHD who perceived
      themselves as more symptomatic often had better WM and were less vulnerable to
      distractions than their ADHD peers.

PMID- 22624706
TI  - Pink Ribbon Pin-Ups: photographing femininity after breast cancer.
AB  - Many treatments for breast cancer are traumatic, invasive and harshly visible. In
      addition to physical trauma, breast cancer is often associated with a variety of
      psychosocial issues surrounding romantic relationships, sexuality and feminine
      identity. Pink Ribbon Pin-Ups was a pin-up girl calendar wherein all the models
      were women who were living with, or had survived, breast cancer. The project's
      purpose was to raise funds and awareness for breast cancer research and to create
      a space where survivors could explore and express their post-cancer sexuality.
      This study uses an observational approach, paired with semi-structured
      interviews, to explore the ways that breast cancer survivors perceive their post
      cancer body and the subsequent impact on relationships and feminine identity. By
      examining contemporary discussions regarding breast cancer, body image and the
      objectification of women, it is concluded that although this photographic
      approach may be at odds with some modern breast cancer activism, it does appear
      to meet the expressed needs of a particular group of women living with the
      disease.

PMID- 22624707
TI  - There's a time and a place for MYCN.
AB  - Brain tumors display extensive diversity. In this issue of Cancer Cell, Swartling
      et al. provide evidence that the temporal and spatial transcriptional programs in
      neural stem cells underlie a diverse response to the MYCN oncogene, potentially
      contributing to cancer diversity.

PMID- 22624708
TI  - What a difference a phosphate makes: life or death decided by a single amino acid
      in MDM2.
AB  - In this issue of Cancer Cell, Gannon and colleagues create genetically engineered
      mice to test the role phosphorylation plays in the modification of one serine
      long thought to play a critical role in controlling the activity of MDM2, one of
      p53's main negative regulators.

PMID- 22624709
TI  - SMIP-016 in action: CD37 as a death receptor.
AB  - CD37 is a tetraspannin that triggers cell death and is a potential therapeutic
      target in cancers. In this issue of Cancer Cell, Lapalombella et al. show that
      CD37 is tyrosine phosphorylated following engagement by a bivalent engineered
      antibody fragment that binds CD37 and activates both SHP-1-dependent apoptotic
      signaling and PI3K-AKT-mediated survival signaling.

PMID- 22624710
TI  - Opening a new GATAway for treating KRAS-driven lung tumors.
AB  - In a recent issue of Cell, Kumar and colleagues uncovered a synthetic lethal
      interaction between oncogenic KRAS and the transcription factor GATA2 in non
      small cell lung carcinoma. Pharmacological inhibition of GATA2-mediated pathways
      with bortezomib and fasudil results in dramatic tumor inhibition. These
      observations unveil new armamentaria to fight this deadly disease.

PMID- 22624712
TI  - Allele-specific p53 mutant reactivation.
AB  - Rescuing the function of mutant p53 protein is an attractive cancer therapeutic
      strategy. Using the National Cancer Institute's anticancer drug screen data, we
      identified two compounds from the thiosemicarbazone family that manifest
      increased growth inhibitory activity in mutant p53 cells, particularly for the
      p53(R175) mutant. Mechanistic studies reveal that NSC319726 restores WT structure
      and function to the p53(R175) mutant. This compound kills p53(R172H) knockin mice
      with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele
      specific mutant p53-dependent manner. This activity depends upon the zinc ion
      chelating properties of the compound as well as redox changes. These data
      identify NSC319726 as a p53(R175) mutant reactivator and as a lead compound for
      p53-targeted drug development.

PMID- 22624711
TI  - Distinct neural stem cell populations give rise to disparate brain tumors in
      response to N-MYC.
AB  - The proto-oncogene MYCN is mis-expressed in various types of human brain tumors.
      To clarify how developmental and regional differences influence transformation,
      we transduced wild-type or mutationally stabilized murine N-myc(T58A) into neural
      stem cells (NSCs) from perinatal murine cerebellum, brain stem, and forebrain.
      Transplantation of N-myc(WT) NSCs was insufficient for tumor formation. N
      myc(T58A) cerebellar and brain stem NSCs generated medulloblastoma/primitive
      neuroectodermal tumors, whereas forebrain NSCs developed diffuse glioma.
      Expression analyses distinguished tumors generated from these different regions,
      with tumors from embryonic versus postnatal cerebellar NSCs demonstrating Sonic
      Hedgehog (SHH) dependence and SHH independence, respectively. These differences
      were regulated in part by the transcription factor SOX9, activated in the SHH
      subclass of human medulloblastoma. Our results demonstrate context-dependent
      transformation of NSCs in response to a common oncogenic signal.

PMID- 22624713
TI  - Lunatic fringe deficiency cooperates with the Met/Caveolin gene amplicon to
      induce basal-like breast cancer.
AB  - Basal-like breast cancers (BLBC) express a luminal progenitor gene signature.
      Notch receptor signaling promotes luminal cell fate specification in the mammary
      gland, while suppressing stem cell self-renewal. Here we show that deletion of
      Lfng, a sugar transferase that prevents Notch activation by Jagged ligands,
      enhances stem/progenitor cell proliferation. Mammary-specific deletion of Lfng
      induces basal-like and claudin-low tumors with accumulation of Notch
      intracellular domain fragments, increased expression of proliferation-associated
      Notch targets, amplification of the Met/Caveolin locus, and elevated Met and Igf
      1R signaling. Human BL breast tumors, commonly associated with JAGGED expression,
      elevated MET signaling, and CAVEOLIN accumulation, express low levels of LFNG.
      Thus, reduced LFNG expression facilitates JAG/NOTCH luminal progenitor signaling
      and cooperates with MET/CAVEOLIN basal-type signaling to promote BLBC.

PMID- 22624714
TI  - S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future
      metastatic sites.
AB  - Recent studies underscore the importance of myeloid cells in rendering distant
      organs hospitable for disseminating tumor cells to colonize. However, what
      enables myeloid cells to have an apparently superior capacity to colonize distant
      organs is unclear. Here, we show that S1PR1-STAT3 upregulation in tumor cells
      induces factors that activate S1PR1-STAT3 in various cells in premetastatic
      sites, leading to premetastatic niche formation. Targeting either S1PR1 or STAT3
      in myeloid cells disrupts existing premetastatic niches. S1PR1-STAT3 pathway
      enables myeloid cells to intravasate, prime the distant organ microenvironment
      and mediate sustained proliferation and survival of their own and other stromal
      cells at future metastatic sites. Analyzing tumor-free lymph nodes from cancer
      patients shows elevated myeloid infiltrates, STAT3 activity, and increased
      survival signal.

PMID- 22624715
TI  - DNA methylation screening identifies driver epigenetic events of cancer cell
      survival.
AB  - Cancer cells typically exhibit aberrant DNA methylation patterns that can drive
      malignant transformation. Whether cancer cells are dependent on these abnormal
      epigenetic modifications remains elusive. We used experimental and bioinformatic
      approaches to unveil genomic regions that require DNA methylation for survival of
      cancer cells. First, we surveyed the residual DNA methylation profiles in cancer
      cells with highly impaired DNA methyltransferases. Then, we clustered these
      profiles according to their DNA methylation status in primary normal and tumor
      tissues. Finally, we used gene expression meta-analysis to identify regions that
      are dependent on DNA methylation-mediated gene silencing. We further showed
      experimentally that these genes must be silenced by DNA methylation for cancer
      cell survival, suggesting these are key epigenetic events associated with
      tumorigenesis.

PMID- 22624716
TI  - ATM phosphorylation of Mdm2 Ser394 regulates the amplitude and duration of the
      DNA damage response in mice.
AB  - DNA damage induced by ionizing radiation activates the ATM kinase, which
      subsequently stabilizes and activates the p53 tumor suppressor protein. Although
      phosphorylation of p53 by ATM was found previously to modulate p53 levels and
      transcriptional activities in vivo, it does not appear to be a major regulator of
      p53 stability. We have utilized mice bearing altered Mdm2 alleles to demonstrate
      that ATM phosphorylation of Mdm2 serine 394 is required for robust p53
      stabilization and activation after DNA damage. In addition, we demonstrate that
      dephosphorylation of Mdm2 Ser394 regulates attenuation of the p53-mediated
      response to DNA damage. Therefore, the phosphorylation status of Mdm2 Ser394
      governs p53 protein levels and functions in cells undergoing DNA damage.

PMID- 22624717
TI  - In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and
      dynamic cell movements in embryonal rhabdomyosarcoma.
AB  - Embryonal rhabdomyosarcoma (ERMS) is an aggressive pediatric sarcoma of muscle.
      Here, we show that ERMS-propagating potential is confined to myf5+ cells and can
      be visualized in live, fluorescent transgenic zebrafish. During early tumor
      growth, myf5+ ERMS cells reside adjacent normal muscle fibers. By late-stage
      ERMS, myf5+ cells are reorganized into distinct regions separated from
      differentiated tumor cells. Time-lapse imaging of late-stage ERMS revealed that
      myf5+ cells populate newly formed tumor only after seeding by highly migratory
      myogenin+ ERMS cells. Moreover, myogenin+ ERMS cells can enter the vasculature,
      whereas myf5+ ERMS-propagating cells do not. Our data suggest that non-tumor
      propagating cells likely have important supportive roles in cancer progression
      and facilitate metastasis.

PMID- 22624719
TI  - SnapShot: glioblastoma multiforme.

PMID- 22624720
TI  - Multisociety sedation curriculum for gastrointestinal endoscopy.

PMID- 22624718
TI  - Tetraspanin CD37 directly mediates transduction of survival and apoptotic
      signals.
AB  - Tetraspanins are commonly believed to act only as "molecular facilitators," with
      no direct role in signal transduction. We herein demonstrate that upon ligation,
      CD37, a tetraspanin molecule expressed on mature normal and transformed B cells,
      becomes tyrosine phosphorylated, associates with proximal signaling molecules,
      and initiates a cascade of events leading to apoptosis. Moreover, we have
      identified two tyrosine residues with opposing regulatory functions: one lies in
      the N-terminal domain of CD37 in a predicted "ITIM-like" motif and mediates SHP1
      dependent death, whereas the second lies in a predicted "ITAM motif" in the C
      terminal domain of CD37 and counteracts death signals by mediating
      phosphatidylinositol 3-kinase-dependent survival.

PMID- 22624721
TI  - Fungal infection in cardiothoracic transplant recipients: outcome without
      systemic amphotericin therapy.
AB  - Transplant recipients require immunosuppression to prevent allograft rejection,
      placing them at risk of opportunistic infections including fungal infection.
      Difficulties in managing fungal infections include: establishing diagnosis, poor
      treatment response, drug interactions and toxicity. We report our single centre
      experience of treating fungal infections using systemic non-Amphotericin current
      generation antifungals. Patients receiving inpatient antifungal therapy from
      September 2005 to December 2010 were identified from pharmacy records. Fungal
      infections were retrospectively classified according to European Organization for
      Research and Treatment of Cancer (EORTC) criteria. Treatment outcomes were
      classified in a manner similar to those used in clinical trials. Two hundred and
      forty-nine recipients received antifungal treatment, 204 lungs and 45 hearts. One
      hundred and one patients received Voriconazole, 82 Caspofungin and 65 received
      both agents. One patient was unsuccessfully treated with additional Amphotericin.
      Treatment duration varied from 1.5 to 12 weeks. One hundred and sixty-five
      patients had a complete response, 24 had a partial response and in 60 patients
      treatment was unsuccessful. The response to systemic non-Amphotericin based
      antifungal therapy was high. We propose that diagnostic criteria without positive
      identification of a fungus allow treatment to be started early with few
      clinically relevant side effects.

PMID- 22624722
TI  - Enrichment of genomic DNA for polymorphism detection in a non-model highly
      polyploid crop plant.
AB  - Large polyploid genomes of non-model species remain challenging targets for DNA
      polymorphism discovery despite the increasing throughput and continued reductions
      in cost of sequencing with new technologies. For these species especially, there
      remains a requirement to enrich genomic DNA to discover polymorphisms in regions
      of interest because of large genome size and to provide the sequence depth to
      enable estimation of copy number. Various methods of enriching DNA have been
      utilised, but some recent methods enable the efficient sampling of large regions
      (e.g. the exome). We have utilised one of these methods, solution-based
      hybridization (Agilent SureSelect), to capture regions of the genome of two
      sugarcane genotypes (one Saccharum officinarum and one Saccharum hybrid) based
      mainly on gene sequences from the close relative Sorghum bicolor. The capture
      probes span approximately 5.8 megabases (Mb). The enrichment over whole-genome
      shotgun sequencing was 10-11-fold for the two genotypes tested. This level of
      enrichment has important consequences for detecting single nucleotide
      polymorphisms (SNPs) from a single lane of Illumina (Genome Analyzer) sequence
      reads. The detection of polymorphisms was enabled by the depth of sequence at or
      near probe sites and enabled the detection of 270 000-280 000 SNPs within each
      genotype from a single lane of sequence using stringent detection parameters. The
      SNPs were present in 13 000-16 000 targeted genes, which would enable mapping of
      a large number of these chosen genes. SNP validation from 454 sequencing and
      between-genotype confirmations gave an 87%-91% validation rate.

PMID- 22624723
TI  - A comparative quality assessment of evidence-based clinical guidelines in
      endocrinology.
AB  - CONTEXT: Evidence-based clinical guidelines in endocrinology attempt to improve
      and standardize patient care. There has been an expansion in guideline production
      although some of the heterogeneous methods used to assess the quality of the
      underlying evidence base might limit interpretation and implementation. DESIGN:
      Current and archived guidelines from major endocrine organizations were accessed.
      The organizations used six different methods to rate underlying evidence,
      including Grading of Recommendations Assessment, Development and Evaluation
      (GRADE). To allow direct comparison between guidelines produced by different
      organizations, the levels of evidence used to generate them were graded according
      to the standardized system: 'high' based on randomized, controlled trials and
      meta-analyses, 'moderate' based on nonrandomized studies and 'low' based on
      expert opinion. RESULTS: There was an increase in guideline production over time
      (1995-2000 = 9, 2001-2005 = 12, 2006-2011 = 36). Three guidelines were updated
      with an average delay of 4.3 years and an increase in recommendations per
      guideline (21.1%). Encouragingly, whilst updates had similar levels of 'high'
      quality evidence, there was increased reliance on 'moderate'-category evidence
      and less on 'low''-quality evidence' ('high', 6.3% vs 6.5%; 'moderate', 46.1% vs
      59.1%; 'low', 47.7% vs 34.4%). A high proportion of 'low'-category evidence was
      seen throughout all organizations. Rarer conditions and recommendations
      concerning treatment efficacy were particularly reliant on 'low'-category
      evidence. CONCLUSIONS: The level of evidence underpinning current guidelines
      highlights areas in need of well-designed, collaborative clinical research.
      Furthermore, criteria to define when guideline updates are necessary are
      currently lacking. A standardized method of assessment, such as GRADE, would
      promote understanding and compliance by guideline users with the ultimate aim of
      enhancing patient care.

PMID- 22624724
TI  - The close relatives of people who have had a traumatic brain injury and their
      special needs.
AB  - PRIMARY OBJECTIVE: This study aims to paint a picture of the needs of people
      close to individuals with a TBI and the services offered to answer these needs,
      from the point of view of the individuals with a TBI and health professionals.
      RESEARCH DESIGN: This study has a qualitative design and a reflexive group was
      used to collect data. The demarche reflexive d'analyse en partenariat, DRAP
      (developing reflexive analysis for partnership) was used as a data collection
      method. The sample comprised Montreal family members (n = 4), Outaouais family
      members (n = 8), Abitibi family members (n = 7); Montreal care providers (n = 9),
      Outaouais care providers (n = 11) and Abitibi care providers (n = 9). MAIN
      OUTCOMES AND RESULTS: The results show that people close to individuals with a
      TBI need information on the health problem, specifically with regard to the
      diagnostic, the prognostic, and the factors that influence it, as well as the
      steps towards rehabilitation, and care and services. The results show that close
      ones need specific, quality services and continuity of services. CONCLUSION: In
      conclusion, the pertinence of this study lies in the desire of close ones and
      health professionals to ease the adaptation process imposed by a TBI, and to
      promote the well-being of informal caregivers.

PMID- 22624725
TI  - Comparative transcriptional analysis of Bacillus subtilis cells overproducing
      either secreted proteins, lipoproteins or membrane proteins.
AB  - BACKGROUND: Bacillus subtilis is a favorable host for the production of
      industrially relevant proteins because of its capacity of secreting proteins into
      the medium to high levels, its GRAS (Generally Recognized As Safe) status, its
      genetic accessibility and its capacity to grow in large fermentations. However,
      production of heterologous proteins still faces limitations. RESULTS: This study
      aimed at the identification of bottlenecks in secretory protein production by
      analyzing the response of B. subtilis at the transcriptome level to
      overproduction of eight secretory proteins of endogenous and heterologous origin
      and with different subcellular or extracellular destination: secreted proteins
      (NprE and XynA of B. subtilis, Usp45 of Lactococcus lactis, TEM-1 beta-lactamase
      of Escherichia coli), membrane proteins (LmrA of L. lactis and XylP of
      Lactobacillus pentosus) and lipoproteins (MntA and YcdH of B. subtilis).
      Responses specific for proteins with a common localization as well as more
      general stress responses were observed. The latter include upregulation of genes
      encoding intracellular stress proteins (groES/EL, CtsR regulated genes). Specific
      responses include upregulation of the liaIHGFSR operon under Usp45 and TEM-1 beta
      lactamase overproduction; cssRS, htrA and htrB under all secreted proteins
      overproduction; sigW and SigW-regulated genes mainly under membrane proteins
      overproduction; and ykrL (encoding an HtpX homologue) specifically under membrane
      proteins overproduction. CONCLUSIONS: The results give better insights into B.
      subtilis responses to protein overproduction stress and provide potential targets
      for genetic engineering in order to further improve B. subtilis as a protein
      production host.

PMID- 22624726
TI  - Outcomes of transplantation using organs from a donor infected with Klebsiella
      pneumoniae carbapenemase (KPC)-producing K. pneumoniae.
AB  - Transmission of pathogens from donor to recipient is a potential complication of
      organ transplantation. Herein, we describe the clinical course and outcomes of 4
      transplant recipients who received tissues from a donor with multi-organ
      infection with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae.
      Recipient 1 underwent simultaneous liver and kidney transplantation for alpha-1
      antitrypsin deficiency and alcohol-related cirrhosis, and acute tubular necrosis,
      respectively. Soon after transplantation, he developed an infected hematoma and
      peritonitis due to KPC-producing K. pneumoniae despite receiving tigecycline
      prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and
      meropenem, in conjunction with surgical evacuation and percutaneous drainage of
      the infected fluid collections. Recipient 2 underwent living-donor liver
      transplantation for cholangiocarcinoma and primary sclerosing cholangitis using
      vein graft from the donor infected with KPC-producing K. pneumoniae. Culture of
      the preservation fluid containing the vein graft was positive for KPC-producing
      K. pneumoniae. The patient received preemptive amikacin and tigecycline, and he
      did not develop any infection (as evidenced by negative surveillance blood
      cultures). The isolates from the donor and Recipients 1 and 2 were
      indistinguishable by pulsed-field gel electrophoresis. Recipients 3 and 4
      underwent kidney and heart transplantation, respectively; both patients received
      perioperative tigecycline prophylaxis and did not develop infections due to KPC
      producing K. pneumoniae. All transplant recipients had good short-term outcomes.
      These cases highlight the importance of inter-institutional communication and
      collaboration to ensure the successful management of recipients of organs from
      donors infected with multidrug-resistant organisms.

PMID- 22624727
TI  - Navitoclax (ABT-263) and bendamustine +/- rituximab induce enhanced killing of
      non-Hodgkin's lymphoma tumours in vivo.
AB  - BACKGROUND AND PURPOSE: Bendamustine with or without rituximab provides an
      effective and more tolerable alternative to the polytherapy cyclophosphamide
      doxorubicin-vincristine-prednisolone (CHOP) in the treatment of haematological
      tumours and is currently approved for the treatment of many haematological
      malignancies. Navitoclax (ABT-263) is a potent inhibitor of Bcl-2, Bcl-x(L) and
      Bcl-w, which has demonstrated efficacy in haematological tumours alone and in
      combination with other agents. This paper describes the in vivo efficacy of
      combining either bendamustine or bendamustine plus rituximab (BR) with navitoclax
      in xenograft models of non-Hodgkin's lymphoma EXPERIMENTAL APPROACH: Activity was
      tested in xenograft models of diffuse large B-cell lymphoma (DoHH-2, SuDHL-4),
      mantle cell lymphoma (Granta 519) and Burkitt's lymphoma (RAMOS). Activity was
      also monitored in a systemic model of Granta 519. KEY RESULTS: Navitoclax
      potentiated bendamustine activity in all cell lines tested. Bendamustine
      activated p53 in Granta 519 tumours, concurrent with activation of caspase 3.
      Navitoclax also improved responses to bendamustine-rituximab (BR) in a subset of
      tumours. CONCLUSIONS AND IMPLICATIONS: Navitoclax in combination with
      bendamustine and BR is a viable combination strategy for use in the clinic and
      demonstrated superior efficacy compared with previously reported data for
      navitoclax plus CHOP and rituximab-CHOP.

PMID- 22624728
TI  - A potent preparation method combining neutralization with microfluidization for
      rebamipide nanosuspensions and its in vivo evaluation.
AB  - BACKGROUNDS: Rebamipide (REB) is classified as a Biopharmaceutics Classification
      System (BCS) Class-IV compound with poor aqueous solubility and poor
      permeability. The local concentration in the mucosa makes REB exhibiting the
      therapeutic activities, and the strategy of increasing the dissolution rate has
      the possibility to improve the oral gastrointestinal (GI) distribution when using
      REB nanosuspensions. OBJECTIVE: The purpose of this work was to prepare REB
      nanosuspensions (REB-NSs) by combining neutralization with microfluidization to
      improve its dissolution rate and orally pharmacokinetic properties. METHODS: The
      feasibility of using acid-base neutralization and microfluidization to prepare
      REB-NSs was studied, and the preparation was optimized by central composite
      design (CCD). Physical states were characterized by using some technical methods,
      while the plasma drug concentration and GI distribution in rodents were
      determined. RESULTS: The experimental results identified a formulation with 10
      mg/mL REB, 0.9% (w/v) Lutrol F127, and 0.6% (w/v) Kollidon 90F. The dissolution
      rate of the dried REB-NSs was faster than that of Mucosta((r)) tablets in
      different media, and the pharmacokinetic study showed a slight increase (1.3-fold
      and 1.1-fold) in the AUC0-12 h compared with unprocessed conventional suspensions
      (CSs) and solutions. Also, the GI distribution of REB-NSs improved compared with
      REB-CSs, and this would be preferable to assist in protecting GI mucosa.
      CONCLUSION: The REB-NSs prepared by the combining method exhibited a higher
      plasma drug concentration and superior GI distribution, thereby demonstrating
      positive results for preparing nanosuspensions of local effective BCS IV drugs
      with pH dependence such as REB by this method.

PMID- 22624729
TI  - Cytokines in schizophrenia: possible role of anti-inflammatory medications in
      clinical and preclinical stages.
AB  - AIMS: In this paper, we review the literature on the efficacy of anti
      inflammatory agents as neuroprotectors in clinical and preclinical stages of
      schizophrenia. METHOD: A synthetic and integrative approach was applied to review
      studies stemming from epidemiology, phenomenology, cognition, genetics and
      neuroimaging data. We provide conclusions and future directions of research on
      early-onset schizophrenia. RESULTS: Abnormal inflammatory activation has been
      demonstrated in schizophrenia. Increases or imbalances in cytokines before birth
      or during childhood may impact neurodevelopment and produce vulnerability to
      schizophrenia. The specificity of inflammatory abnormalities in psychiatric
      disorders is controversial. Similar increases in pro-inflammatory cytokines have
      been described in other disorders, especially mood and anxiety disorders. One of
      the most important challenges at this point is the understanding of
      neurobiological correlates of prodromal stages of schizophrenia. CONCLUSION:
      Although future research should investigate the exact role of different cytokines
      in pathophysiology of schizophrenia, these mediators emerge as promising
      molecular targets to its prevention and treatment.

PMID- 22624730
TI  - State and trait markers of emotionally charged visual event-related potentials
      (P300) in drug-naive schizophrenia.
AB  - AIM: In the present study, we investigated the changes in P3 component in the
      emotionally charged visual event-related potentials (ERP) in 30 drug-naive
      schizophrenic patients for up to 1 year. METHODS: Visual oddball event-related
      potential was recorded from six recording sites for crying baby or smiling baby
      photographs. ERP were recorded before the treatment (session 1 [S1]), after 3
      months (session 2 [S2]), and after 12 months (session 3 [S3]), as well as in 30
      healthy subjects. RESULTS: Before taking medicine, there were no significant
      differences in the P300 amplitude between viewing photographs of a crying and a
      smiling baby. The P300 amplitude was significantly larger at S2 and S3 than at S1
      for a crying baby, while there was no significant difference among sessions for a
      smiling baby after medication. A significant difference of the P300 amplitude was
      only observed between S3 and healthy subjects for a smiling baby. The P300
      latency only when viewing a smiling face became significantly longer at S3 than
      those at S1 and S2. A significant negative correlation was obtained between the
      P300 amplitude changes upon viewing crying faces and negative syndrome score
      changes at the Pz site. CONCLUSION: The P300 amplitude induced by crying-face
      stimuli may be a state marker and the P300 amplitude caused by smiling-face
      stimuli may be a trait marker during recovery in schizophrenic patients. Atypical
      antipsychotic medications may be useful and may recover cognitive function
      reflected by the emotionally charged visual P300 components in schizophrenic
      patients.

PMID- 22624731
TI  - Object relations in adolescence: a comparison of normal and inpatient
      adolescents.
AB  - AIMS: We aimed to study the development of object relations in adolescents and
      their correlation with their mothers' defense styles in inpatient and normal
      adolescents. METHODS: We administered the Thematic Apperception Test to
      adolescents in the adolescent unit (junior high, n = 16; senior high, n = 22) and
      normal controls (junior high, n = 16; senior high, n = 16). Results were analyzed
      using the Complexity of Representations Scale (CRS). We administered the Defense
      Style Questionnaire (DSQ(40)) to the subjects' mothers (patients, n = 38;
      controls, n = 32) to determine whether adolescents' CRS scores correlated with
      mothers' DSQ scores. RESULTS: There was a nearly significant interaction for
      group-by-school-year for the children's CRS scores. In the control group, senior
      high school students' scores (mean [SD] = 3.52 [0.49]) were significantly higher
      (F [1,66] = 12.3, P = 0.001) than those of junior high school students' (mean
      [SD] = 3.03 [0.31]). In the patient group, no significant difference was observed
      between senior high and junior high. For mothers' DSQ(40), mature defense scores
      were significantly higher in the control group than in the patient group (mean
      [SD] = 10.8 [1.89] vs 9.35 [1.40] in junior high, and 11.8 [1.67] vs 9.36 [1.81]
      in senior high, F [1,66] = 22.1, P < 0.001, two-way ANOVA). A significant,
      positive correlation (r = 0.37, P = 0.04) was observed between the mothers'
      mature defense and the children's CRS scores in the control group only.
      CONCLUSIONS: Whatever diagnoses are provided, the problems of adolescents with
      non-psychotic pathologies are related to the arrest of object relations
      development. A patient's mother cannot employ mature mechanisms to alleviate
      signals of anxiety sent by her child.

PMID- 22624732
TI  - Differential relationships between personality and brain function in monetary and
      goal-oriented subjective motivation: multichannel near-infrared spectroscopy of
      healthy subjects.
AB  - AIM: To examine relationships between personality traits and cerebral cortex
      reactivity under different motivating conditions. METHODS: Relationships between
      personality traits assessed using the NEO Personality Inventory-Revised (NEO-PI
      R) and cerebral cortex reactivity during a verbal fluency task monitored using
      multichannel near-infrared spectroscopy (NIRS) were examined under three
      different motivational conditions: control, monetary reward, and goal-oriented,
      in healthy young male volunteers. RESULTS: Significant correlations between
      cerebral cortex reactivity and personality traits were found in the frontopolar
      region: a positive correlation with agreeableness and a negative correlation with
      the neuroticism and conscientiousness scores of the NEO-PI-R under the three
      motivational conditions. Higher scores for agreeableness were more strongly
      associated with a greater increase in total hemoglobin concentration ([total-Hb])
      under the goal-oriented and control conditions than under the monetary reward
      condition. In addition, higher scores for neuroticism were more strongly
      associated with a greater increase in deoxygenated hemoglobin concentration
      ([deoxy-Hb]) under the monetary reward condition than the goal-oriented
      condition, and higher scores for conscientiousness were more strongly associated
      with a greater increase in [deoxy-Hb] under control conditions than under the
      goal-oriented condition. CONCLUSION: Using multichannel NIRS, certain personality
      traits of the big-five model are related to frontopolar reactivity. These
      relationships vary depending on the motivational condition when brain functions
      are monitored: agreeableness, neuroticism, and conscientiousness are all related
      to frontopolar reactivity depending on the motivational condition.

PMID- 22624733
TI  - Time course of the development of depressive mood and oppositional defiant
      behavior among boys with attention deficit hyperactivity disorder: differences
      between subtypes.
AB  - AIM: The aim of this research was to clarify the development of depression among
      boys with attention deficit hyperactivity disorder (ADHD) by examining the
      correlation between depressive mood, oppositional defiant behavior, and age for
      each ADHD subtype. METHODS: The Birleson Depression Self-Rating Scale (DSRS) was
      used to evaluate depressive mood while the Oppositional Defiant Behavior
      Inventory (ODBI) was used to evaluate oppositional defiant behavior. The 90
      subjects were divided into three groups: 22 boys (mean age, 12.4 +/- 1.9 years)
      were placed in the ADHD predominantly inattentive type (ADHD-I) group; 45 boys
      (mean age, 10.4 +/- 2.0 years) were placed in the ADHD combined type (ADHD-C)
      group; and 23 boys (mean age, 12.7 +/- 2.4 years) were placed in the depressive
      disorder (DD) group. The DD group was included to highlight characteristics of
      depressive mood among boys with ADHD. RESULTS: The DSRS score was significantly
      higher in the DD group compared to the ADHD-I and ADHD-C groups. The ODBI score
      was significantly higher in the ADHD-C group compared to the ADHD-I (P = 0.043)
      and DD (P = 0.013) groups. In the DD group, ODBI was seen to decrease with
      increasing age. A certain degree of oppositional defiant behavior was seen in
      each ADHD subtype. The DSRS score correlated with the ODBI score in the ADHD-C
      group, while the DSRS score correlated with age in the ADHD-I group. CONCLUSION:
      The characteristics of developing depressive mood in childhood ADHD appeared to
      differ between subtypes and also differed from depression without ADHD.

PMID- 22624734
TI  - Psychosocial and psychiatric characteristics of suicide completers with
      psychiatric treatment before death: a psychological autopsy study of 76 cases.
AB  - AIM: The present study was conducted to examine differences in psychosocial and
      psychiatric characteristics between suicide completers with and without a history
      of psychiatric treatment within the year before death, using a psychological
      autopsy method. METHODS: A semi-structured interview was administered by a
      psychiatrist and other mental health professionals for the closest bereaved of 76
      suicide completers. RESULTS: Suicide completers with a history of psychiatric
      treatment (n = 38) were significantly younger than those without (n = 38) (P <
      0.01), and a significantly higher proportion of cases in the treatment group were
      estimated to be suffering from schizophrenia. Further, in 57.9% of the treatment
      group, the fatal suicidal behavior involved overdose with prescribed psychotropic
      drugs. In addition, female suicide completers in the treatment group were more
      likely to have a history of self-harm or non-fatal suicidal behavior. CONCLUSION:
      Many suicide completers who received psychiatric treatment were young adults. It
      was common for suicide completers to overdose on prescribed drugs as a
      supplementary means of suicide, and many experienced self-harming behavior before
      death. In addition, a higher proportion of the treatment cases suffered from
      schizophrenia.

PMID- 22624735
TI  - Pilot study of deep brain stimulation in refractory obsessive-compulsive disorder
      ethnic Chinese patients.
AB  - AIMS: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum
      (VC/VS) is a promising alternative to ablative surgery in treatment of refractory
      obsessive-compulsive disorder (OCD). A pilot study was conducted to assess 15
      month outcomes of DBS in patients with refractory OCD in Taiwan. METHODS: Four
      adult patients with a 3-year or more history of refractory OCD (Yale-Brown
      Obsessive-Compulsive Scale [Y-BOCS] score of at least 28) met the criteria for
      DBS surgery. DBS electrodes were implanted bilaterally in the VC/VS. Stimulation
      was adjusted for therapeutic benefit and absence of adverse effects. Psychiatric
      evaluation was conducted preoperatively, postoperatively, and at follow up at
      every 3 months for 15 months. Primary outcome measure was Y-BOCS. Secondary
      outcomes included the Hamilton Depression Rating Scale (HAM-D), and the Global
      Assessment of Function Scale. RESULTS: Mean severity of OCD was a Y-BOCS score of
      36.3 +/- 2.1. At the end of 15 months' follow up, there was a 33.06% decrease in
      OCD severity (P = 0.001). Similar findings were seen for HAM-D (32.51% reduction,
      P = 0.005), and Global Assessment of Function Scale (31.03% increase, P = 0.026).
      In terms of adverse effects, two patients suffered from hypomania episodes after
      several weeks of DBS stimulation, and one had transient hypomania-like syndrome
      during DBS initial programming. One patient (Case 1) had an allergic reaction to
      implantation of the pulse generator in the chest, and another patient (Case 3)
      exhibited vertigo. CONCLUSIONS: We confirm that DBS of the VC/VS appears to be
      beneficial for improvements in function and mood among patients with treatment
      resistant OCD. Compared to previous studies examining the therapeutic effects of
      DBS, no serious adverse effects were observed.

PMID- 22624736
TI  - Improved outcomes following a switch to olanzapine treatment from risperidone
      treatment in a 1-year naturalistic study of schizophrenia patients in Japan.
AB  - AIMS: This study assessed clinical and functional outcomes following a switch
      from risperidone to olanzapine in a 1-year naturalistic study of schizophrenia
      patients in Japan. METHODS: We used data from a large 1-year prospective,
      multicenter, observational non-interventional study of individuals who were
      initiated on olanzapine for the treatment of schizophrenia in Japan. Current
      analyses focused on patients who were switched at study entry from risperidone to
      olanzapine (n = 258). Repeated measures analysis was employed to assess outcomes
      on validated measures. RESULTS: At study entry, 45% were inpatients and 55%
      outpatients. Participants were in their early 40s with mean illness duration of
      14 years. Approximately half were male. Most were switched from risperidone to
      olanzapine due to poor medication efficacy (67.8%) rather than medication
      intolerability (29.1%). Most patients (67.8%) completed the 1-year study.
      Patients experienced clinically and statistically significant (P < 0.05)
      improvements in global symptom severity, positive, negative, depressive, and
      cognitive symptoms, health-related quality of life, and paid work rates. Most
      patients (59.2%) demonstrated treatment response to olanzapine and 43.4%
      experienced symptom remission. Mean weight gain was 2.19 kg, with one-third of
      patients (33.3%) experiencing clinically significant weight gain (>=7%).
      CONCLUSIONS: In this 1-year naturalistic study, inpatients and outpatients who
      were switched from risperidone to olanzapine experienced clinically and
      statistically significant improvements in their clinical and functional outcomes.
      One-third of all patients experienced clinically significant weight gain. Current
      findings highlight the favorable benefit-to-risk profile of switching to
      olanzapine therapy following treatment failure on risperidone among patients with
      schizophrenia in Japan.

PMID- 22624737
TI  - Normal mind-reading capacity but higher response confidence in borderline
      personality disorder patients.
AB  - AIM: Borderline personality disorder (BPD) is characterized by a pattern of
      instability in interpersonal relationships. Therefore, the investigation of
      social cognition is of compelling interest for the understanding of BPD. One
      important aspect of social cognition is theory of mind (ToM), which describes the
      ability to understand others' mental states, such as beliefs, desires and
      intentions. The aim of the present study was to further investigate ToM in BPD
      patients. METHODS: The Reading the Mind in the Eyes Test was assessed in 31 BPD
      patients and 27 healthy controls. In addition, the test was complemented by a
      response confidence rating. RESULTS: BPD patients and healthy controls did not
      differ in their mind-reading ability with respect to accuracy, but patients were
      significantly more often highly confident in their decisions than controls.
      CONCLUSIONS: Overconfidence might contribute to the severe difficulties in
      interpersonal relationships often observed in BPD patients.

PMID- 22624738
TI  - Effects of an assertive community program in patients with severe mental
      disorders and impact on their families.
AB  - AIMS: Assertive community treatment (ACT) is known to have a positive impact on
      the number and length of inpatient stays. However, recent studies have shown
      little or no effect of such programs in European settings. This paper aims to
      describe the impact of a newly implemented ACT program on patients and their
      families' burden. Predictive factors have also been examined. METHOD: Fifty-five
      patients characterized by heavy use of psychiatric care, numerous
      hospitalizations, or failure to link with outpatient psychiatric care and their
      relatives were followed. Data were gathered on patients before and after follow
      up as well as on relatives' burden and costs. The number and domains of clinician
      interventions have been detailed. RESULTS: The ACT program had a positive effect
      on symptoms, psychosocial adaptation and quality of life. Age was the most
      significant predictor of changes. Older patients, most of them suffering from
      delusional disorders, showed no improvement or even some impairment. Finally, the
      program appeared to have a marked effect on easing families' burden in domains
      such as assistance in daily life activities and costs. CONCLUSIONS: ACT appears
      to be recommended for patients with poor outcome when treated in other settings.
      Early intervention seems to be justified as highlighted by younger age being the
      best predictor of positive changes. Families can be helped considerably,
      particularly those confronted with patients with persistent disturbing symptoms
      which do not, however, warrant hospitalization. Finally, the fact that patients
      with delusional disorder do not seem to improve warrants further research.

PMID- 22624739
TI  - Serotonin 1A receptor genetic variations, suicide, and life events in the Iranian
      population.
AB  - AIM: The association of serotonin 1A receptor (5-HTR1A) gene polymorphisms with
      suicidal behavior has been reported in several previous studies, but the results
      have been inconsistent, which might be due to ethnic differences. The aim of the
      present study was therefore to investigate the association between polymorphisms 
      1019C>G, 47C>T (Pro16Leu) and 815G>A (Gly272Asp) and suicidal behavior, taking
      into account age, gender, and the presence of stressful life and loss events in 1
      year prior to suicide. METHODS: A total of 191 suicide victims and 218 healthy
      control subjects were included in the present study. 5-HT1RA gene polymorphisms
      were determined on polymerase chain reaction-restriction fragment length
      polymorphism. RESULTS: The distribution of -1019C>G genotypes was significantly
      different in suicide victims and healthy controls (P = 0.002), and the GG
      genotype was associated with a significantly higher number of more stressful life
      and loss events in the suicide victims (P = 0.017, P = 0.037, respectively). The
      distribution of 47C>T (Pro16Leu) and 815G>A (Gly272Asp) genotypes was not
      significantly different in the suicide victims and control subjects (P > 0.05).
      Moreover, these genotypes were not associated with stressful life and loss events
      (P > 0.05). CONCLUSION: The frequency of the -1019G allele in the 5-HTR1A gene
      was higher in suicide victims (with stressful life events) as compared with the
      control group. In contrast, neither 47C>T (Pro16Leu) nor 815G>A (Gly272Asp)
      polymorphisms were related with suicide and stressful life events.

PMID- 22624740
TI  - Resting motor threshold changes and clinical response to prefrontal repetitive
      transcranial magnetic stimulation in depressed patients.
AB  - AIMS: Several variables are able to influence the antidepressant effects of
      repetitive transcranial magnetic stimulation (rTMS), particularly the intensity
      of stimulation, which is generally expressed according to the resting motor
      threshold (RMT). The aim of our study was to investigate whether or not RMT
      changes during the treatment of resistant depression by rTMS and whether these
      fluctuations could alter treatment outcome. METHODS: Seventy-five inpatients
      suffering from unipolar or bipolar treatment-resistant depression and who had
      been antidepressant-free or taking a stable antidepressant drug and a daily dose
      of benzodiazepine for at least a month received a left prefrontal rTMS session
      once a day for 10 days at 10 Hz and 95% RMT. RESULTS: For the whole group, no
      significant fluctuation of RMT was observed between the first and the second week
      of rTMS treatment. However, RMT increased, decreased or remained constant
      throughout treatment depending on the patient. These RMT changes influenced the
      outcome of the 10 sessions concerning the severity of depressive and anxiety
      symptoms, measured by the Beck Depression Inventory and State Trait Anxiety,
      respectively. CONCLUSIONS: Our results justify calculating RMT regularly, and
      suggest that its variations play a role in treatment outcome.

PMID- 22624741
TI  - Psychological impact of the pandemic (H1N1) 2009 on general hospital workers in
      Kobe.
AB  - AIMS: In order for hospitals to work efficiently in a pandemic, it is important
      to know how a pandemic affects the hospital staff. The aim of the present study
      was to investigate the psychological impact of the pandemic (H1N1) 2009 on
      hospital workers and how it was affected by the characteristics of the hospital,
      gender, age, job and work environment. METHODS: In late June 2009, soon after the
      pandemic had ended in Kobe city, Japan, a questionnaire was distributed
      consisting of questions on sociodemographic characteristics, 19 stress-related
      questions and the Impact of Event Scale (IES) to all 3635 employees at three core
      general hospitals in Kobe. Exploratory factor analysis was applied to the 19
      stress-related questions, and this produced four factors for evaluation (anxiety
      about infection, exhaustion, workload, and feeling of being protected). Multiple
      regression models were used to evaluate the association of personal
      characteristics with each score of the four factors and the IES. RESULTS: Valid
      answers were received from 1625 employees. Workers at a hospital with intense
      liaison psychiatric services felt less psychological impact. Workers at a
      hospital that provided staff with information about the pandemic less frequently,
      felt unprotected. Workers in work environments that had a high risk of infection
      felt more anxious and more exhausted. The total IES score was higher in workers
      in high-risk work environments. CONCLUSIONS: It is important for hospitals to
      protect hospital workers during a pandemic and to rapidly share information about
      the pandemic. Liaison psychiatric services can help to reduce the impact of the
      pandemic on hospital workers.

PMID- 22624742
TI  - Heart rate variability in the subsyndromal depressive phase of bipolar disorder.
AB  - AIMS: To compare the heart rate variability of bipolar patients in the
      subsyndromal depressive phase with healthy controls and to evaluate the
      relationship between severity of subsyndromal depressive symptoms and heart rate
      variability. METHODS: Thirty-three bipolar patients in the subsyndromal
      depressive phase and 59 healthy controls were enrolled. A patient was considered
      to be in a subsyndromal depressive phase when the Montgomery-Asberg depression
      rating scale score was <=10 and the Clinical Global Impression-Severity scale
      (CGI-S) was <=3 for the previous 1 month. After approximately 10 min of supine
      rest, all participants underwent resting electrocardiograms for 5 min in the
      supine position using limb leads. Different parameters of heart rate variability
      were analyzed in the time and frequency domains. RESULTS: Bipolar patients had
      significantly lower standard deviation of all RR intervals (SDNN), proportion of
      adjacent NN intervals that differ by >50 ms (pNN50), log total power (log TP) and
      very low frequency power (VLF) compared to healthy controls. There were
      significant negative correlations between CGI-S score and some heart rate
      variability parameters, including heart rate variability index, SDNN, root mean
      square successive difference (RMSSD), pNN50, log TP, VLF, low frequency power
      (LF) and high frequency power (HF). CONCLUSION: Patients with bipolar disorder in
      the subsyndromal depressive state have reduced heart rate variability relative to
      healthy controls, and reduction of heart rate variability appears to be
      correlated with severity of symptoms in bipolar patients.

PMID- 22624743
TI  - Association of lower hemoglobin levels with depression, though not with cognitive
      performance, in healthy elderly men.
AB  - Lower hemoglobin (Hb) levels are a common feature in the elderly. The present
      study recruited 180 healthy elderly men. Participants were assessed using the
      Geriatric Depression Scale, the Cognitive Abilities Screening Instrument Chinese
      version, and the Wechsler Digit Span Task test. The mean age of the participants
      was 85.8 years (SD = 10.5). Pearson's correlation tests demonstrated that Hb
      concentrations negatively correlated with Geriatric Depression Scale (r = -0.245,
      P = 0.001), but did not correlate with Cognitive Abilities Screening Instrument,
      Forward or Backward Digit Span tests. Lower Hb levels, therefore, were associated
      with depression in the elderly men.

PMID- 22624744
TI  - Hyposmia in Parkinson's disease.

PMID- 22624746
TI  - Does the growth rate of total amount in cash salaries relate to a transition in
      the suicide rate?

PMID- 22624745
TI  - Improvement in quetiapine-induced hypoglycemia following a switch to blonanserin.

PMID- 22624747
TI  - Minimum 2-year follow up of sex reassignment surgery in Brazilian male-to-female
      transsexuals.

PMID- 22624748
TI  - Dentists' marketing to consumers - what's the point?

PMID- 22624749
TI  - Root caries and diabetes: risk assessing to improve oral and systemic health
      outcomes.
AB  - This report reviews the current understanding of the relationship between
      diabetes and root caries, and investigates the evidence for dental chairside
      testing of gingival crevicular blood (GCB) glucose levels to assess risk for type
      2 diabetes mellitus. Diabetes is linked with the progression of periodontal
      disease and a greater number of exposed root surfaces at risk for root caries.
      The rapidly increasing prevalence of type 2 diabetes coupled with a general trend
      towards retention of teeth means that the number of patients with increased risk
      for root caries is expanding significantly. Many patients with diabetes or
      abnormal blood glucose levels are unaware of their condition or that they are at
      increased risk for oral disease. Systemic blood glucose concentrations are
      comparable to those found in GCB and therefore may be a useful adjunctive
      clinical aid in determining appropriate care for patients and providing timely
      referrals to general medical practitioners. Use of GCB testing within the dental
      clinic is described. It is proposed that future studies be undertaken to provide
      clinicians with improved risk assessment strategies and to evaluate GCB glucose
      screening models.

PMID- 22624750
TI  - Accessory roots in maxillary molar teeth: a review and endodontic considerations.
AB  - Maxillary molar teeth may have accessory roots. The aim of this paper is to
      review and discuss the endodontic implications of this anatomical variation. A
      review of the literature was undertaken to identify studies and reported cases
      where accessory roots have been recorded in maxillary molar teeth. The results
      show that although the prevalence of accessory roots in maxillary molar teeth is
      low, they can exist in all three types of maxillary molar teeth, and they may be
      located palatally, buccally, mesially or distally. Hence, it is essential that
      dentists undertaking root canal treatment thoroughly assess all teeth to
      determine how many roots are present in order to provide the best possible
      outcome of treatment for the patient.

PMID- 22624751
TI  - A three-year retrospective study of emergency visits at an oral health clinic in
      south-east Queensland.
AB  - BACKGROUND: There is little information available regarding dental emergencies
      for children in Australia. The aim of this study was to investigate the reasons
      for dental emergency cases which were treated at a public oral health clinic in a
      low socioeconomic district in south-east Queensland. METHODS: From a register
      kept at a public oral health clinic, we analysed the monthly number of emergency
      visits for children over a three-year period (January 2008 to August 2010) with
      respect to numbers treated, reasons for presentation and types of treatment
      rendered. RESULTS: During the period 2008-2010, there was a mean of 196 +/- 86
      cases presenting for emergency care each month. The proportions of the various
      types of emergencies remained fairly consistent over the three-year period, with
      the majority presenting for caries related problems (74-75%), followed by trauma
      (8-9%), orthodontic treatment related (2-5%) and other reasons (16-11%). Between
      8-11% of cases were preschool children who were added to the waitlist for
      treatment for caries under general anaesthesia at the public hospital.
      CONCLUSIONS: Trends in the past three years at a public oral health clinic in a
      low socioeconomic district in south-east Queensland show that dental caries
      constitute nearly three-quarters of all paediatric emergency appointments.

PMID- 22624752
TI  - Adhesion to Er:YAG laser and bur prepared root and crown dentine.
AB  - BACKGROUND: The purpose of this study was to evaluate the bond strengths between
      dentine and resin composite obtained after Er:YAG laser treatment of crown or
      root dentine used together with self-etch and total-etch adhesive systems.
      METHODS: One etch-and-rinse adhesive (Single Bond, 3M, USA) and one self-etch
      system (Clearfil SE Bond, Kuraray, Japan) were applied to root and crown dentine
      prepared with a regular bur in a turbine or with an Er:YAG laser. The shear bond
      strength was determined after thermocycling and statistically analysed using
      independent t-tests. RESULTS: Crown sites bonded using Clearfil SE Bond and
      Single Bond adhesives yielded bond strengths similar to that of root dentine
      sites (p > 0.05). Clearfil SE Bond was stronger in both the lased and non-lased
      groups (p < 0.05). The lowest bond strength was obtained when Single Bond without
      acid etching was used on Er:YAG ablated dentine. When total-etch adhesive was
      used, there were significant differences (p < 0.05) between the laser-ablated and
      laser-ablated/acid-etched and bur-cut/acid-etched groups. CONCLUSIONS: Er:YAG
      laser irradiation of root and crown dentine conducted prior to the adhesive
      protocol adversely affected adhesion and decreased bond strength compared with
      traditional preparation.

PMID- 22624753
TI  - Outcomes of moderate sedation in paediatric dental patients.
AB  - BACKGROUND: The aim of this study was to evaluate the outcomes of moderate
      sedation with nitrous oxide/oxygen (N(2) O/O(2)) alone or combined with different
      dosages and administration routes of midazolam in uncooperative paediatric dental
      patients using the Bispectral Index System (BIS). METHODS: This one-year clinical
      study examined first-visit moderate sedation performed in 240 healthy children
      aged 4-6 years. Subjects were randomly divided into four groups according to
      drug, route and dosage, as follows: Group 1 - 0.20 mg/kg midazolam (40 mg/ml)
      delivered intranasally; Group 2 - 0.75 mg/kg midazolam (15 mg/3 ml) delivered
      orally; Group 3 - 0.50 mg/kg midazolam (15 mg/3 ml) delivered orally. All
      children in these three groups also received inhalation sedation with 50%-50%
      N(2) O/O(2), whereas children in Group 4 received inhalation sedation with 50%
      50% N(2) O/O(2) only. The outcome of sedation was evaluated as either
      'successful', 'failed' or 'not accepted'. RESULTS: The highest success rate was
      found in Group 1 (0.20 mg/kg intranasally, 87%), followed by Group 2 (0.75 mg/kg
      orally, 79%). The overall mean success rate for all groups was 73%. CONCLUSIONS:
      Moderate sedation can be successfully used in the clinical management of
      paediatric dental patients, with both intranasal and oral sedation using
      midazolam in conjunction with nitrous oxide found to be effective methods.

PMID- 22624754
TI  - Enamel roughness and depth profile after phosphoric acid etching of healthy and
      fluorotic enamel.
AB  - BACKGROUND: Dental fluorosis requires aesthetic treatment to improve appearance
      and etching of enamel surfaces with phosphoric acid is a key step for adhesive
      restorations. The aim of this study was to evaluate surface roughness and a depth
      profile in healthy and fluorotic enamel before and after phosphoric acid etching
      at 15, 30 and 60 seconds. METHODS: One hundred and sixty enamel samples from
      third molars with no fluorosis to severe fluorosis were evaluated by atomic force
      microscopy. RESULTS: Healthy enamel showed a statistically significant difference
      (p < 0.05) between mean surface roughness at 15 seconds (180.3 nm), 30 seconds
      (260.9 nm) and 60 seconds (346.5 nm); depth profiles revealed a significant
      difference for the 60 second treatment (4240.2 nm). For mild fluorosis, there was
      a statistically significant difference (p < 0.05) between mean surface roughness
      for 30 second (307.8 nm) and 60 second (346.6 nm) treatments; differences in
      depth profiles were statistically significant at 15 seconds (2546.7 nm), 30
      seconds (3884.2 nm) and 60 seconds (3612.1 nm). For moderate fluorosis, a
      statistically significant difference (p < 0.05) was observed for surface
      roughness for 30 second (324.5 nm) and 60 second (396.6 nm) treatments.
      CONCLUSIONS: Surface roughness and depth profile analyses revealed that the best
      etching results were obtained at 15 seconds for the no fluorosis and mild
      fluorosis groups, and at 30 seconds for the moderate fluorosis group. Increasing
      the etching time for severe fluorosis decreased surface roughness and the depth
      profile, which suggests less micromechanical enamel retention for adhesive
      bonding applications.

PMID- 22624755
TI  - Effect of ginsenoside Rg1 on proliferation and differentiation of human dental
      pulp cells in vitro.
AB  - BACKGROUND: Human dental pulp cells (hDPCs) have the potency to proliferate and
      differentiate into odontoblasts and play an important role in dentine formation
      and reparation. The aim of the present study is to evaluate the effects of
      ginsenoside Rg1 on the proliferation and differentiation of hDPCs. METHODS: hDPCs
      were incubated with different concentrations of ginsenoside Rg1 (0.1, 0.5, 2.5,
      5, 10 and 20 MUmol/L). The effects of ginsenoside Rg1 on the proliferative
      ability of hDPCs were evaluated by a fibroblast colony forming test, MTT assay
      and flow cytometry for cell cycle. The control group, osteogenic induction group,
      ginsenoside Rg1 (5 MUmol/L) group and combination group were designed, and
      alkaline phosphatase (ALP) activity and FQ-PCR for gene expressions of dentine
      sialophosphoprotein (DSPP) and dentine matrix protein 1 (DMP1) were performed to
      evaluate the differentiation of hDPCs. RESULTS: The proliferative ability of
      hDPCs in ginsenoside Rg1 was significantly enhanced (p < 0.05), especially in the
      ginsenoside Rg1 (5 MUmol/L) group. ALP activity and gene expressions of DSPP and
      DMP1 were increased in the induction group, ginsenoside Rg1 group, and their
      combination group compared with the control group (p < 0.05). CONCLUSIONS: The
      results indicate that ginsenoside Rg1 promotes the proliferation and
      differentiation of hDPCs.

PMID- 22624756
TI  - The effect of calcium silicate-based sealer on the push-out bond strength of
      fibre posts.
AB  - BACKGROUND: The aim of this study was to assess the effect of the iRoot SP root
      canal sealer on the push-out bond strength of fibre posts cemented with self
      adhesive resin cement. METHODS: Forty-eight extracted maxillary incisors were
      randomly divided into four groups according to the tested sealer (n = 12): group
      1 - control (only gutta-percha points, no sealer); group 2 - AH Plus Jet (resin
      based sealer); group 3 - Endofill (zinc oxide-eugenol-based sealer); and group 4 
      iRoot SP (calcium silicate-based sealer). All root canals were filled with gutta
      percha, and groups 2-4 additionally received one of the sealers. Fibre posts were
      cemented with the self-adhesive resin cement Clearfil SA Cement. The specimens
      were sectioned in the coronal, middle and apical regions, producing three slices
      of 1 mm thickness. The push-out test was performed. All data were submitted to
      ANOVA and Tukey tests (alpha = 0.05). RESULTS: No statistically significant
      differences were found between the control group, AH Plus Jet and iRoot SP (p >
      0.05). The Endofill sealer showed significantly lower bond strength compared to
      the other sealers and the control group (p < 0.05). CONCLUSIONS: The calcium
      silicate-based sealer did not adversely affect the bond strength of the fibre
      posts cemented with self-adhesive resin cement.

PMID- 22624757
TI  - Location of main occluding areas and masticatory ability in patients with implant
      supported prostheses.
AB  - BACKGROUND: The purpose of this study was to locate the main occluding area when
      the reduced posterior occlusal support was treated with an implant-supported
      prosthesis and to evaluate the subsequent improvement in the masticatory ability
      as compared with removable partial dentures. METHODS: Twenty-six patients with
      implant prostheses and 24 patients with removable partial dentures were recruited
      for this study. All patients had partially lost their posterior occlusal support.
      The first molar region in any quadrant was always included in the prosthetic
      region. Each subject was instructed to clench a piece of temporary stopping as a
      test food on the occluding area that was preferably used during mastication. The
      main occluding area was judged by locating the tooth on which the temporary
      stopping rested during clenching. Subjective masticatory ability was self
      assessed by means of a questionnaire. RESULTS: The main occluding area of the
      subjects in the implant group was located more posterior compared with the
      removable partial denture group. The level of masticatory ability in the implant
      group was the same as that in the control group. CONCLUSIONS: The location of the
      main occluding area and the masticatory ability of the subjects with implants
      were equivalent to those with healthy natural dentition.

PMID- 22624758
TI  - The effect of repeated fluoride recharge and storage media on bond durability of
      fluoride rechargeable Giomer bonding agent.
AB  - BACKGROUND: For a restorative material or adhesive to exhibit caries inhibitive
      potential through fluoride release, it must be capable of fluoride recharge. The
      aim of this study was to evaluate the effect of repeated fluoride recharge and
      different storage media on dentine bond strength durability. METHODS: Two self
      etch adhesive systems (two-step) were evaluated: fluoride-rechargeable Giomer FL
      Bond II and non-fluoride-containing UniFil Bond. For each adhesive 32 human
      dentine specimens were prepared for shear bond strength testing. The specimens
      were randomly allocated to one of four storage groups: Group 1 - 24-hour water
      ageing; Group 2 - four-month water ageing; Group 3 - four-month water ageing with
      weekly fluoride recharge (5000 ppm for 10 minutes); and Group 4 - four-month acid
      ageing with weekly fluoride recharge. RESULTS: Weekly fluoride recharge over four
      months ageing did not significantly (p > 0.05) reduce the dentine shear bond
      strength of FL-Bond II or UniFil Bond. Storage media did not significantly (p >
      0.05) affect bond durability. CONCLUSIONS: The adhesion between fluoride
      rechargeable FL-Bond II and dentine maintained durability despite regular
      fluoride recharge over the four months ageing. Clinicians prescribing the
      fluoride recharge regime used in the present study to reduce recurrent caries
      incidence associated with Giomer FL-Bond II restorations can do so without
      compromising dentine bond strengths.

PMID- 22624759
TI  - A comparative analysis of the accuracy of different direct impression techniques
      for multiple implants.
AB  - BACKGROUND: The aim of this study was to compare the accuracy of different direct
      implant impression techniques for edentulous arches with multiple implants.
      METHODS: Five experimental groups (n = 5) were assembled. Experimental models
      were created by a direct splinted technique (EG2 to EG5) and a non-splinted
      technique (EG1). In EG2 and EG3 synOcta impression copings were splinted with an
      acrylic resin bar, and in EG4 and EG5 with a light-curing composite resin bar. In
      EG3 and EG5 the resin bars were sectioned, while the other experimental groups
      were not. Three-dimensional discrepancies were measured by a computerized
      coordinate measuring machine. Distortion values among the groups were analysed
      using one-way repeated measures ANOVA. The post hoc Tukey's test was then
      performed for multiple comparisons. RESULTS: The highest accuracy was obtained in
      EG2 (mean deviation: 12.70 MUm). The acrylic bars demonstrated less deviation
      (12.70 MUm and 22.71 MUm) from the master model than the light-curing composite
      resin groups and the non-splinted group (41.09 MUm). The post hoc Tukey's test
      showed no significant difference among the groups when the effect of splint
      design on accuracy was investigated. CONCLUSIONS: For situations where
      impressions of multiple implants are to be made, splinting impression copings
      with acrylic resin demonstrate superior results than the non-splinted technique
      and splinting with light-curing composite.

PMID- 22624761
TI  - Validation of micro-CT against the section method regarding the assessment of
      marginal leakage of sealants.
AB  - BACKGROUND: The aim of this study was to validate the micro-CT and related
      software against the section method using the stereomicroscope for marginal
      leakage assessment along the sealant-enamel interface. METHODS: Pits and fissures
      of the occlusal surface of 10 teeth were sealed with a resin-fissure sealant
      material without acid etching, thermocycled for 5000 cycles, immersed in 50%
      silver nitrate for three hours and scanned using micro-CT. Teeth were embedded in
      epoxy resin and cut in three sections. The middle section was subjected to micro
      CT and stereomicroscopy. Images were taken from the left and right sides of the
      sealant-enamel interface at both the left and the right site of the section. Two
      experienced evaluators assessed marginal leakage. RESULTS: Both assessment
      instruments observed no leakage in 37 out of the 40 images evaluated. Leakage at
      the sealant-enamel interface was observed in three stereomicroscopy images only.
      A fracture line in the sealant was seen on eight stereomicroscopy images and
      observed in only two micro-CT images. CONCLUSIONS: The quality of the micro-CT
      and related software used in the present study does not qualify it to replace the
      section method as the gold standard for marginal leakage assessment at the
      sealant-enamel interface of permanent teeth.

PMID- 22624760
TI  - Enamel demineralization and bracket bond strength when etching with acid and /or
      Er:YAG laser.
AB  - BACKGROUND: Enamel etching for brackets is usually done with phosphoric acid.
      Er:YAG lasers have been recently used for this purpose with conflicting results.
      The effects of lasers on tooth demineralization and the effects of different
      combinations of laser treatments and bonding agents were evaluated in this study.
      METHODS: The enamel contents of fluorine, calcium oxide and phosphorus pentoxide
      (P(2) O(5)) were analysed using acid etching, laser treatment or both. The
      tensile bond strength of metallic and ceramic brackets using Transbond XT and
      Fuji Ortho LC were also tested, using acid etching, laser treatment or a
      combination of both. RESULTS: All treatments reduced the contents of fluorine,
      P(2)O(5) and calcium oxide, and acid reduced P(2) O(5) levels more than laser.
      The bond strength with laser was weaker than with acid, and stronger when
      combining both. When using laser, the best adhesive was the Fuji Ortho LC. The
      combination of laser and acid produced the best results when using Transbond XT.
      CONCLUSIONS: The demineralization promoted by laser was lower than the one
      produced with acid. Laser treatment produced lower tensile stress strength than
      acid, but still enough to produce clinically efficient retention. The combination
      of laser and acid produced the best retention results.

PMID- 22624762
TI  - Bone regeneration in sinus augmentation procedures with calcium sulphate.
      Microstructure and microanalytical investigations.
AB  - BACKGROUND: The aim of this study was a histological and ultrastructural
      evaluation of the bone formed in human sinus augmentation procedures with calcium
      sulphate (CaS). METHODS: Scanning electron microscopy (SEM) and energy dispersive
      X-ray spectroscopy (EDS) were used to evaluate the relationship between CaS and
      newly-formed bone, while birefringence was used to evaluate the bone structure
      around the CaS particles by polarized light microscopy. Unstained sections were
      studied with an Axiovert 200 M using the fluorescence in reflected UV light to
      evaluate the interface between CaS and newly-formed bone. Twenty specimens
      retrieved from the sinus after a healing period of six months were studied.
      RESULTS: EDS analysis of six specimens showed that little sulphur remained and
      residual particles appeared to have transformed to calcium phosphate. Under
      polarized light a few biomaterial remnants were present in some areas and covered
      by mature bone. The relationship between residual particles and bone due to the
      different photon emission under UV light stimulation was observed under
      fluorescence microscopy. CONCLUSIONS: The present results confirm the high
      biocompatibility and rapid resorption rate of CaS. The mechanism of
      transformation of CaS to calcium phosphate, already demonstrated in animal
      studies, has been confirmed in the present human study.

PMID- 22624763
TI  - Platelet-rich fibrin increases cell attachment, proliferation and collagen
      related protein expression of human osteoblasts.
AB  - BACKGROUND: Platelet-rich fibrin (PRF) prepared by Choukroun's technique is
      derived from an autogenous preparation of concentrated platelets without any
      manipulation. PRF was found to increase osteoblast growth and proliferation.
      However, the underlying mechanisms are not yet completely understood. This study
      aimed to determine the effects of PRF on cell attachment, proliferation,
      phosphorylated Akt, heat shock protein 47 (HSP47) and lysyl oxidase (LOX)
      expression on human osteoblasts. METHODS: Blood collection was carried out from
      10 healthy volunteers. Cell attachment and proliferation were measured by
      colorimetric assay with WST-1 and alamar blue in human osteoblast cell line U2OS
      cells, respectively. Western blot was employed to evaluate the expression of p
      Akt, HSP47 and LOX. RESULTS: PRF alone was found to stimulate U2OS cell
      attachment compared with untreated controls (p < 0.05). PRF was found to increase
      osteoblast proliferation during a 5-day incubation period (p < 0.05). PRF was
      found to increase Akt phosphorylation in a time-dependent manner (p < 0.05).
      Collagen-related proteins HSP47 and LOX were significantly elevated by
      stimulation with PRF compared with untreated controls (p < 0.05). CONCLUSIONS: It
      is suggested that PRF is capable of increasing osteoblast attachment,
      proliferation and simultaneously upregulating collagen-related protein
      production. These actions in combination would effectively promote bone
      regeneration.

PMID- 22624764
TI  - Tooth whitening with hydrogen/carbamide peroxides in association with a CPP-ACP
      paste at different proportions.
AB  - BACKGROUND: Different enhanced peroxide formulations have been developed to
      overcome mineral loss during tooth whitening. This study investigated the impact
      on tooth whitening from combining a CPP-ACP paste with home peroxide agents at
      several proportions. METHODS: Ninety bovine incisors were randomly allocated into
      nine groups (n = 10) and exposed to 7.5% hydrogen peroxide (HP), 16% carbamide
      peroxide (CP), a CPP-ACP paste (Tooth Mousse/MI Paste, GC Corporation, Tokyo,
      Japan) and blends of HP/CP:MI at three proportions (1:1, 2:1 and 1:2). Tooth
      whitening was performed for 14 days and its effectiveness was measured by a
      spectrophotometer utilizing the CIE L*a*b* system (DeltaE, DeltaL*, Deltaa* and
      Deltab*). Colour readings were measured at baseline (T0), 7 days of bleaching
      (T7), 14 days of bleaching (T14) and 7 days after the end of bleaching (T21).
      Data were analysed by two-way ANOVA for paired averages followed by the Tukey's
      test and Pearson's correlation at 5%. RESULTS: Although CP produced the greatest
      colour change (DeltaE), all whitening protocols were considered to be effective
      regardless of the CPP-ACP presence. In general, greater changes in DeltaE,
      DeltaL*, Deltaa* and Deltab* were detected at T14, with T21 exhibiting similar
      results to those at T7. A greater number of strong correlations with DeltaE
      values was found for a* (11/15). CONCLUSIONS: Within the limitations of this
      study, the results indicate that the CPP-ACP paste did not affect tooth whitening
      efficacy.

PMID- 22624765
TI  - Influence of phosphoric acid etching on microleakage of a self-etch adhesive and
      a self-adhering composite.
AB  - BACKGROUND: The aim of this study was to evaluate the influence of preliminary
      phosphoric acid etching on the microleakage of a self-adhering flowable composite
      and a self-etch adhesive used in combination with the proprietary flowable
      composite. METHODS: Standard Class V cavities were prepared on the buccal side of
      20 extracted sound human molars. Specimens were randomly divided into five
      groups: (1) Gel Etchant/Optibond FL/Premise Flowable; (2) Vertise Flow; (3)
      Optibond XTR/Premise Flowable; (4) Gel Etchant/Vertise Flow; and (5) Gel
      Etchant/Optibond XTR/Premise Flowable (Kerr). The interfacial sealing ability of
      the materials was evaluated by scoring the depth of silver nitrate penetration
      and through scanning electron microscopy observations. Differences in leakage at
      either the enamel or the dentine interface were evaluated for statistical
      significance (Kruskal-Wallis ANOVA, Mann-Whitney U test, p < 0.05). RESULTS: At
      the enamel interface, no significant differences were found among the materials.
      On dentine, Gel Etchant/Vertise Flow had the highest leakage scores and the
      difference was statistically significant (p < 0.05). CONCLUSIONS: The early
      sealing ability of the self-adhering flowable composite and the self-etch
      adhesive in Class V restorations did not significantly benefit from selective
      enamel etching. Preliminary phosphoric acid etching of dentine negatively
      affected the quality of the seal when using the adhesive-free flowable composite.

PMID- 22624766
TI  - Radical surgical treatment of bisphosphonate related osteonecrosis of the jaw.
AB  - We describe a case of a 64-year-old female diagnosed with multiple myeloma in
      2001. She was treated with pamidronate and subsequently zolodronic acid before
      developing spontaneous bisphosphonate related osteonecrosis (BRONJ) of the left
      maxilla in December 2008. Over the next two years the BRONJ was treated
      conservatively but gradually became more symptomatic. About three years after her
      last dose of zolodronic acid with her symptoms increasing, she underwent radical
      surgical excision of all diseased bone and flap reconstruction. The patient is
      now six months postoperative and symptom free.

PMID- 22624767
TI  - Mandibular angle fractures during third molar removal: a report of two cases.
AB  - Although fracture of the tooth during surgical removal is common, mandibular
      fracture during lower third molar removal is an unusual and major complication.
      Possible aetiologies are age, gender, the position of the tooth, uncontrolled
      excessive force applied, insufficient surgical experience and improper
      instrumentation. Symptoms can vary widely and treatment options range from
      prescription of a soft diet to surgical treatment by open reduction and internal
      fixation. We present two cases of the treatment and follow-up of fracture of the
      angle region of the mandible during removal.

PMID- 22624768
TI  - Exotic encounters with dental implants: managing complications with unidentified
      systems.
AB  - As the application of dental implants increases worldwide, so is the number of
      technical and biological complications that general dental practitioners will be
      called to manage, while maintaining implant patients. In addition, the greater
      patient mobility encountered today combined with a growing trend of 'dental
      implant tourism' will very often result in situations where the dentist is
      requested to deal with complications in implants placed elsewhere and which
      sometimes might be of an 'exotic' system one cannot directly recognize. Such a
      situation can pose significant challenges to even experienced clinicians. The
      challenges are not only in the scientific field, but often include professional
      and ethical implications. This case report will discuss strategies for the
      management of implant complications in cases of unidentified implant systems.
      Critical factors in such situations would be the clinician's experience and
      special training, the correct radiographic technique, as well as access to the
      appropriate tools and devices.

PMID- 22624771
TI  - Assessment of bone grafts.

PMID- 22624774
TI  - Effects of host physiology on the development of core rot, caused by alternaria
      alternata, in Red Delicious apples.
AB  - Alternaria alternata is the predominant fungus involved in moldy core and core
      rot of Red Delicious apples. The effects of environmental conditions during bloom
      on moldy core and core rot, and on the need for fungicide application, were
      examined in 10 experiments carried out in 2007. In untreated experimental plots,
      typical moldy core symptoms were very common, with relatively low variability
      (coefficient of variation: 22.2%) among experiments; core rot incidence ranged
      from 2 to 26% with large variability (coefficient of variation: 90.0%) among
      experiments. No evidence of prevailing environmental conditions during bloom
      affecting the development of moldy core or core rot was detected. No effect of
      fungicide application (a mixture of bromuconazole + captan three times a week at
      bloom) on moldy core or core rot was found. A random distribution of moldy core
      and an occasional aggregation of core rot in the orchards were indicated from
      Morisita's index of dispersion (I(delta)). The hypothesis that core rot incidence
      is governed by host physiology and that yield load can be used as an indicator of
      trees' susceptibility was examined in a set of eight observations and four
      experiments. No correlation was found between tree yield load and moldy core, but
      core rot incidence was inversely related to yield load. Furthermore, irrespective
      of tree yield load, core rot was more abundant on large compared with small
      fruits. It is concluded that host physiology, rather than pathogen occurrence or
      environmental conditions at bloom stage, governs the development of core rot in
      Red Delicious apples caused by A. alternata in Israel.

PMID- 22624773
TI  - LNA probes substantially improve the detection of bacterial endosymbionts in
      whole mount of insects by fluorescent in-situ hybridization.
AB  - BACKGROUND: Detection of unculturable bacteria and their localization in the
      host, by fluorescent in-situ hybridization (FISH), is a powerful technique in the
      study of host-bacteria interaction. FISH probes are designed to target the 16 s
      rRNA region of the bacteria to be detected. LNA probes have recently been used in
      FISH studies and proven to be more efficient. To date no report has employed LNA
      probes for FISH detection of bacterial endosymbiont in the whole mount tissues.
      Further, though speculated, bacteriocytes have not been reported from males of
      Bemisia tabaci. RESULTS: In this study, we compared the efficiency in detecting
      bacteria by fluorescent DNA oligonucleotides versus modified probes containing
      Locked Nucleic Acid (LNA) substitution in their structure. We used the insect
      Bemisia tabaci as the experimental material since it carried simultaneous
      infection by two bacteria: one a primary endosymbiont, Portiera (and present in
      more numbers) while the other a secondary endosymbiont Arsenophonus (and present
      in less numbers). Thus a variation in the abundance of bacteria was expected.
      While detecting both the bacteria, we found a significant increase in the signal
      whenever LNA probes were used. However, the difference was more pronounced in
      detecting the secondary endosymbiont, wherein DNA probes gave weak signals when
      compared to LNA probes. Also, signal to noise ratio for LNA probes was higher
      than DNA probes. We found that LNA considerably improved sensitivity of FISH, as
      compared to the commonly used DNA oligonucleotide probe. CONCLUSION: By employing
      LNA probes we could detect endosymbiotic bacteria in males, which have never been
      reported previously. We were able to detect bacteriocytes containing Portiera and
      Arsenophonus in the males of B. tabaci. Thus, employing LNA probes at optimized
      conditions will help to significantly improve detection of bacteria at the lowest
      concentration and may give a comprehensible depiction about their specific
      distribution within samples.

PMID- 22624775
TI  - Observations of assisted feeding among people with language impairment.
AB  - AIMS AND OBJECTIVES: This study examines the phenomenon of assisted feeding among
      people with language impairment. BACKGROUND: Patients' experience of assisted
      feeding is influenced by the caregivers' availability and their other
      responsibilities. Also, caregivers and patients may have different values with
      respect to assisted feeding. METHODS: Instances of assisted feeding (n=42) were
      observed among people with language impairment admitted to a neurological ward.
      Field notes were taken simultaneously and in some cases a few simple questions
      were posed to the caregivers or the patients. All notes and answers were analysed
      using the phenomenological guidelines of Dahlberg and colleagues (2008,
      Studentlitteratur AB, Stockholm). RESULT: The essence of assisted feeding among
      people living with language impairment was identified to be a transaction
      characterised by efficiency. The constituents of the essence were in the shadow
      of institutional structures, accidental relationships with potential humiliation,
      meal-related conventions versus respect for the individual's wishes, sense of joy
      threatened by goal-related determination' time being significant for the course
      of the meal. CONCLUSION: This study shows that assisted feeding is not important
      enough to postpone other activities in a neurological ward. Although assisted
      feeding is an opportunity to enjoy mutual contact and exchange information
      between the patient and the caregiver, it is a situation where the nutritional
      aspect of the meal tends to take precedence. We recommend that the focus of
      recent years on the patients' nutritional status is now supplemented by
      improvement in the relational and affective aspects of meals, especially for
      people who require assistance to eat. RELEVANCE TO CLINICAL PRACTICE: The
      findings indicate that the institutional conditions for meals need to be
      reconsidered. For instance caregivers could be exempted from other
      responsibilities during mealtimes. More flexible time-limits for meals depending
      on the number of patients with extensive assistance needs is another possibility.

PMID- 22624777
TI  - Management of gynecologic surgery in the patient with factor XI deficiency: a
      review of the literature.
AB  - Factor XI deficiency is a rare bleeding disorder that is more commonly found in
      Ashkenazi Jews. Bleeding manifestations of this disorder are varied and poorly
      correlate with factor XI levels. Spontaneous bleeding is uncommon, whereas
      delayed postoperative bleeding is often the presentation of factor XI deficiency.
      To date, there are no standard recommendations for prophylactic treatment in
      women undergoing gynecologic surgery. Here, we review published cases of
      gynecological surgery in women with factor XI deficiency and discuss the risks
      and benefits of various therapeutic options. TARGET AUDIENCE: Obstetricians And
      Gynecologists. LEARNING OBJECTIVES: After participating in this activity,
      physicians should be better able to identify the pathophysiology of factor XI
      deficiency. Compare previous outcomes of prophylactic treatment in patients with
      factor XI deficiency undergoing gynecological surgery. Implement possible
      prophylactic therapies for patients with factor XI deficiency undergoing
      gynecological surgery.

PMID- 22624778
TI  - Maternal arrhythmia: a case report and review of the literature.
AB  - Pregnant patients with maternal arrhythmias can be challenging and difficult to
      treat. Medication choices may be limited in patients who are pregnant. Pregnancy
      carries with it a unique and complex physiology, coupled with fetal concerns. We
      describe a pregnant patient with an arrhythmia to illustrate treatment thought
      process and options. We also present a comprehensive review of the literature in
      regard to treatment of maternal arrhythmias and their potential adverse fetal and
      maternal outcomes. These treatments include antiarrhythmic medications,
      electrical cardioversion, and radiofrequency ablation. Antepartum and intrapartum
      monitoring will also be addressed along with delivery planning and postpartum
      considerations. The most important aspect in treating these patients is the use
      of a multidisciplinary approach. The decision of what therapy to use must be
      addressed on a case-by-case basis with special attention to the patient's
      individual issues and concerns. TARGET AUDIENCE: Obstetricians and gynecologists,
      family physicians, emergency room physicians LEARNING OBJECTIVES: After
      completion of this educational activity, the obstetrician/gynecologist should be
      better able to assess and council patients on the risks and complications of
      maternal arrhythmias in pregnancy. Evaluate the current treatment options
      available for health care providers caring for pregnant patients with maternal
      arrhythmia, and manage the antepartum course, labor, and delivery in these
      patients.

PMID- 22624776
TI  - An interdisciplinary knowledge translation intervention in long-term care: study
      protocol for the vitamin D and osteoporosis study (ViDOS) pilot cluster
      randomized controlled trial.
AB  - BACKGROUND: Knowledge translation (KT) research in long-term care (LTC) is still
      in its early stages. This protocol describes the evaluation of a multifaceted,
      interdisciplinary KT intervention aimed at integrating evidence-based
      osteoporosis and fracture prevention strategies into LTC care processes. METHODS
      AND DESIGN: The Vitamin D and Osteoporosis Study (ViDOS) is underway in 40 LTC
      homes (n = 19 intervention, n = 21 control) across Ontario, Canada. The primary
      objectives of this study are to assess the feasibility of delivering the KT
      intervention, and clinically, to increase the percent of LTC residents prescribed
      >=800 IU of vitamin D daily. Eligibility criteria are LTC homes that are serviced
      by our partner pharmacy provider and have more than one prescribing physician.
      The target audience within each LTC home is the Professional Advisory Committee
      (PAC), an interdisciplinary team who meets quarterly. The key elements of the
      intervention are three interactive educational sessions led by an expert opinion
      leader, action planning using a quality improvement cycle, audit and feedback
      reports, nominated internal champions, and reminders/point-of-care tools. Control
      homes do not receive any intervention, however both intervention and control
      homes received educational materials as part of the Ontario Osteoporosis
      Strategy. Primary outcomes are feasibility measures (recruitment, retention,
      attendance at educational sessions, action plan items identified and initiated,
      internal champions identified, performance reports provided and reviewed), and
      vitamin D (>=800 IU/daily) prescribing at 6 and 12 months. Secondary outcomes
      include the proportion of residents prescribed calcium supplements and
      osteoporosis medications, and falls and fractures. Qualitative methods will
      examine the experience of the LTC team with the KT intervention. Homes are
      centrally randomized to intervention and control groups in blocks of variable
      size using a computer generated allocation sequence. Randomization is stratified
      by home size and profit/nonprofit status. Prescribing data retrieval and analysis
      are performed by blinded personnel. DISCUSSION: Our study will contribute to an
      improved understanding of the feasibility and acceptability of a multifaceted
      intervention aimed at translating knowledge to LTC practitioners. Lessons learned
      from this study will be valuable in guiding future research and understanding the
      complexities of translating knowledge in LTC.

PMID- 22624779
TI  - Postpartum depression in special populations: a review.
AB  - This review article aims to define and characterize postpartum depression; to
      discuss the social, financial, regulatory and legal implications of the disorder;
      and to elucidate its impact on special groups, namely adolescents, immigrants,
      fathers, and those of different racial and ethnic groups. A MEDLINE review of the
      current literature was run on postpartum depression, using the key words
      postpartum depression, depression, pregnancy, peripartum, or postpartum, from the
      years 2000 to 2011. Postpartum depressive syndromes place women and their
      children at risk of suicide and infanticide if not appropriately diagnosed and
      treated. Screening should occur within 4 to 6 weeks postpartum. Women with a
      history of depression before or during pregnancy, adolescents, those with low
      incomes and poor social support, or with a history of substance abuse, are
      especially at high risk. Treatments include antidepressants and psychotherapy.
      The unique populations of adolescents, fathers, immigrants, and certain racial
      and ethnic groups require special consideration in terms of diagnosis, screening
      modalities, and treatment. Collaboration between obstetrical providers and
      behavioral health professionals can ensure improved outcomes. It was found that
      postpartum depression is a challenging diagnosis and may be difficult to treat. A
      multidisciplinary approach is warranted to prevent life-threatening consequences
      in mothers and their children. TARGET AUDIENCE: Obstetricians & Gynecologists,
      Family Physicians LEARNING OBJECTIVES: After participating in this activity,
      physicians should be better able to diagnose postpartum depression and to analyze
      the social, financial, regulatory and legal implications of the disorder; and to
      evaluate its impact on special groups, namely adolescents, immigrants, fathers,
      and those of different racial and ethnic groups.

PMID- 22624780
TI  - A new approach on Brewer's spent grains treatment and potential use as
      lignocellulosic yeast cells carriers.
AB  - The major objective of this work is to improve the pretreatments of brewer's
      spent grains (BSG) aiming at their use as a source for lignocellulosic yeast
      carriers (LCYC) production. Therefore, several pretreatments of BSG have been
      designed aiming at obtaining various yeast carriers, differing on their
      physicochemical composition. Cellulose, hemicellulose, lignin, fat, protein, and
      ash content were determined for crude BSG and the LCYCs. The long chain fatty
      acids profile for the crude BSG was also analyzed. Chemical treatments
      successfully produced several different LCYC based on BSG. The highest cellulose
      content in LCYC was achieved upon application of caustic (NaOH) treatment during
      40 min. Either caustic or combined acid-caustic treatments predominately
      generated hydrophobic, negatively charged LCYC. The feasibility of using BSG for
      LCYC production is strengthened by the fact that added-value byproduct can be
      extracted before the chemical treatments are applied. 

PMID- 22624781
TI  - JHS guidelines on systematic review and meta-analysis submissions.

PMID- 22624782
TI  - Lunatocapitate and triquetrohamate arthrodeses for degenerative arthritis of the
      wrist.
AB  - PURPOSE: Proximal row carpectomy and 4-corner arthrodesis are 2 well-established
      motion-preserving treatment strategies for scapholunate advanced collapse. In
      this study, we present an arthrodesis technique involving the capitolunate and
      triquetrohamate joints as another potential treatment option. METHODS: From 2000
      to 2009, 27 consecutive patients with degenerative scapholunate advanced collapse
      and scaphoid nonunion advanced collapse were evaluated prospectively and treated
      with scaphoid excision and intercarpal arthrodesis between the capitate and
      lunate and between the hamate and triquetrum. This cohort consisted of 18 men and
      9 women, involving dominant-sided surgery in 20 of 27 patients. Two patients were
      active smokers, and 3 cases were work related. Average age at time of surgery was
      55 +/- 3 years, and average follow-up was 51 +/- 7 months. Preoperative and
      postoperative range of motion, grip strength, and radiographic evidence of
      osseous union were documented. Standardized Patient-Rated Wrist Evaluation scores
      for both pain and function were collected. RESULTS: Wrist extension and flexion
      were decreased after surgery by 17% and 25% respectively, yielding a 21% decrease
      in mean flexion-extension arc. There was no significant difference with regard to
      postoperative radial and ulnar deviation or mean coronal plane arc compared to
      preoperative values. Compared to the contralateral side, preoperative and
      postoperative grip strength were 53% and 70%, respectively. The average operative
      sided grip strength increased by 27%. The mean Patient-Rated Wrist Evaluation
      pain score was 11 +/- 3 (of 50). The mean Patient-Rated Wrist Evaluation
      functional score was 17 +/- 5 (of 100). Complications included 1 nonunion
      (yielding a 96% fusion rate), 1 median neuropathy (which resolved), and 2
      superficial wound infections (treated successfully with oral antibiotics).
      CONCLUSIONS: Arthrodesis of the capitolunate and triquetrohamate joints offers a
      motion-preserving strategy with a high union rate and good clinical function and
      pain outcomes for the treatment for scapholunate advanced collapse and scaphoid
      nonunion advanced collapse. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22624783
TI  - The durability of the intrascaphoid compression of headless compression screws:
      in vitro study.
AB  - PURPOSE: To test a new generation of compression screws: the Acumed Acutrak 2
      Mini (AA; Acumed, Hillsboro, OR), the Stryker TwinFix (ST; Stryker, Kalamazoo,
      MI), and the Synthes 3.0 headless compression screw (SH; Synthes, Solothurn,
      Switzerland). METHODS: We used 40 fresh-frozen human scaphoids for this study.
      Bone density was measured. A K-wire was inserted centrally. A perpendicular
      osteotomy was created in the middle third (Herbert B2 fracture). A custom-made
      load sensor was placed between the bone fragments. All screws were implanted
      according to the manufacturers' instructions. The Synthes 2.0 cortical screw
      (SC), implanted as a lag screw, was used as a reference. The compression force
      during each experiment was digitally monitored for 12 hours while the data were
      acquired. The data were analyzed using analysis of variance with the Bonferroni
      correction. RESULTS: Immediately after screw insertion, ST reached 226 N,
      followed by AA with 191 N, SH with 137 N, and SC with 72 N. After 12 hours, ST
      displayed the highest residual compression force, 141 N, followed by AA with 121
      N, SH with 78 N, and SC with 32 N. The differences were significant for ST and AA
      compared to SC. The loss of compression force over 12 hours was 39% for ST, 42%
      for AA, 49% for SH, and 55% for SC. CONCLUSIONS: The new generation of headless
      compression screws, especially ST and AA, provided significantly higher
      compression forces after 12 hours, as well as the least loss of compression force
      over time, in comparison to a classic cortical lag screw. CLINICAL RELEVANCE: A
      new generation of headless compression screws, by producing higher compression
      forces, increase stability at the fracture site and might thereby promote bone
      healing.

PMID- 22624784
TI  - The vascularization of the median nerve in the distal forearm and its potential
      clinical importance.
AB  - PURPOSE: The aims of this anatomical study were to identify any extrinsic blood
      supply to the median nerve in the distal forearm and to measure the tension
      required to approximate the severed nerve after and before dissecting it while
      maintaining its extrinsic blood supply. METHODS: We injected the arterial system
      of 15 lightly embalmed forearms with red latex to define the vascular anatomy of
      the median nerve in the distal forearm. We measured the gap resulting from
      spontaneous retraction of the cut ends of the divided median nerve and the
      average tension needed to reapproximate the ends before and after resection of
      the attachments to the nerve on its superficial, deep, and ulnar aspects.
      RESULTS: A constant branch to the median nerve arises from the radial artery
      approximately 5 cm proximal to the radial styloid process. The mean gap between
      the severed nerve ends was 1.2 cm (range, 0.9-1.7 cm). The mean tension required
      to coapt the nerve ends was 231 g force (range, 200-280 g), reducing to 89 g
      force (range, 60-110 g) when only its radial attachments, including this vessel,
      were preserved. CONCLUSIONS: This cadaveric study suggests that it may be
      possible to advance the median nerve at the wrist while retaining the vascular
      connection and blood supply from the radial artery, and so maintain the
      vascularity of the nerve at the common site of nerve repair in the distal
      forearm. CLINICAL RELEVANCE: This cadaveric study identifies constant arterial
      feeding branches from the radial artery to the median nerve in the distal
      forearm, and is a preliminary investigation into the possibility of advancing the
      median nerve for repair in the distal forearm while maintaining the continuity of
      this branch.

PMID- 22624785
TI  - Comparison of splinting versus nonsplinting in the treatment of pediatric trigger
      finger.
AB  - PURPOSE: Because pediatric trigger finger is much less common than pediatric
      trigger thumb, there is no consensus on the efficacy of splinting, owing to both
      the rarity of the condition and a lack of natural history and comparative
      therapeutic data. We performed the present retrospective study on 47 fingers to
      compare pediatric trigger finger treatment by splinting and nonsplinting.
      METHODS: We included 24 children with a total of 47 trigger fingers. Affected
      fingers included 4 index, 28 middle, 11 ring, and 4 little fingers. Patient age
      at initial examination ranged from 1 month to 9 years (mean, 2 y). We observed 24
      fingers treated with a static splint and 23 fingers treated without it. The time
      from initial examination to follow-up ranged from 2 to 18 years. RESULTS: In the
      splinting group, 16 fingers (67%) resolved, 4 fingers (17%) improved, and 4
      fingers (17%) remained unchanged. Seven fingers (29%) ultimately required
      surgery. In the nonsplinting group, 7 fingers (30%) resolved spontaneously, 1
      (4%) improved, and 15 (65%) remained unchanged. Fifteen fingers (65%) later
      underwent surgical release. The rate of resolution in the splinting group was
      significantly higher than that in the nonsplinting group. The proportion of
      fingers needing surgical treatment in the splinting group was significantly lower
      than that in the nonsplinting group. CONCLUSIONS: For treatment of pediatric
      trigger finger, it is advisable to fit a static splint at the first visit. TYPE
      OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22624786
TI  - The anterolateral corner of the radial metaphysis as a source of bone graft for
      the treatment of scaphoid nonunion.
AB  - As a source of corticocancellous grafts for treating scaphoid nonunions, the
      anterolateral corner of the distal radial metaphysis has several advantages over
      other alternatives: it provides good-quality corticocancellous bone, it allows
      one to harvest the graft and treat the scaphoid through the same incision, it
      does not require general anesthesia, and it has less morbidity than occurs when
      obtaining the graft from the iliac crest.

PMID- 22624787
TI  - Another light in the dark: review of a new method for the arthroscopic repair of
      triangular fibrocartilage complex.
AB  - The triangular fibrocartilage complex (TFCC) is an anatomically and
      biomechanically important structure. Repair of radial-sided TFCC tear has
      previously been challenging. We designed a new method of radial-sided TFCC tear
      repair and found that it was also applicable for ulnar-sided TFCC tear repair.
      From October 2006 to December 2010, 10 patients underwent this operation and were
      reviewed: 9 men and 1 woman, with a mean age of 33.9 years. Average postoperative
      follow-up was 8 months. We graded results according to the Mayo modified wrist
      score. We rated 2 of the 10 patients (20%) as "excellent," 3 (30%) as "good," and
      5 (50%) as "fair." The 5 patients who were rated as "fair" returned to regular
      jobs or had restricted employment. Based on this small sample, we recommend that
      this technique be considered an alternative method for TFCC repair.

PMID- 22624788
TI  - Lessons for adult fingertip regeneration: glimpses from basic research.
AB  - Understanding the mechanisms involved in limb and finger regeneration holds
      promise for improving current treatment therapies. Recent animal studies have
      improved our understanding of the limb regeneration process markedly. Improved
      sophistication in experimentation has allowed results that partly reveal the
      cells of origin in fingertip regeneration in mouse models, which implicates a
      tissue-resident progenitor cell population. The impressive regeneration of
      amputated salamander limbs has been shown to work through an evolutionarily
      divergent mechanism and may not be open to direct translational approaches in
      mammals. In addition, researchers are beginning to understand the complexity of
      the interrelated mechanisms of axis determinants in chick embryo limb
      development. In this article, we review lessons to be learned from these
      divergent experiments, to understand fingertip regeneration in humans.

PMID- 22624789
TI  - Paul R. Manske 2011 award for best upper extremity congenital research
      manuscript.

PMID- 22624790
TI  - Occurrence of the non-native annual bluegrass on the Antarctic mainland and its
      negative effects on native plants.
AB  - Few non-native species have colonized Antarctica, although increased human
      activity and accelerated climate change may increase their number, distributional
      range, and effects on native species on the continent. We searched 13 sites on
      the maritime Antarctic islands and 12 sites on the Antarctic Peninsula for annual
      bluegrass (Poa annua), a non-native flowering plant. We also evaluated the
      possible effects of competition between P. annua and 2 vascular plants native to
      Antarctica, Antarctic pearlwort (Colobanthus quitensis) and Antarctic hairgrass
      (Deschampsia antarctica). We grew the native species in experimental plots with
      and without annual bluegrass under conditions that mimicked the Antarctic
      environment. After 5 months, we measured photosynthetic performance on the basis
      of chlorophyll fluorescence and determined total biomass of both native species.
      We found individual specimens of annual bluegrass at 3 different sites on the
      Antarctic Peninsula during the 2007-2008 and 2009-2010 austral summers. The
      presence of bluegrass was associated with a statistically significant reduction
      in biomass of pearlwort and hairgrass, whereas the decrease in biomass of
      bluegrass was not statistically significant. Similarly, the presence of bluegrass
      significantly reduced the photosynthetic performance of the 2 native species.
      Sites where bluegrass occurred were close to major maritime routes of scientific
      expeditions and of tourist cruises to Antarctica. We believe that if current
      levels of human activity and regional warming persist, more non-native plant
      species are likely to colonize the Antarctic and may affect native species.

PMID- 22624791
TI  - Noninvasive, quantitative, spatiotemporal characterization of mineralization in
      three-dimensional collagen hydrogels using high-resolution spectral ultrasound
      imaging.
AB  - As tissue engineering products move toward the clinic, nondestructive methods to
      monitor their development and ensure quality are needed. In this study, high
      resolution spectral ultrasound imaging (SUSI) was used to noninvasively
      characterize mineral content in collagen hydrogels. SUSI was used to generate
      three-dimensional (3D) grayscale (GS) images of construct morphology with
      submillimeter resolution. Spectral analysis of the backscattered radio frequency
      (RF) ultrasound signals was used to determine the midband fit (MBF) and slope of
      the linearized RF spectrum. These parameters are operator and instrument
      independent, and were used to characterize the spatial distribution of mineral in
      constructs supplemented with hydroxyapatite particles. GS and MBF correlated
      closely with mineral content, while slope was not dependent on concentration.
      SUSI also was used to monitor mineralization of collagen constructs by immersion
      in simulated body fluid (SBF) over 21 days. The construct surface was mineralized
      before the interior, and there was a dose-dependent effect of SBF concentration
      on degree of mineralization and deposited particle size. MBF density was closely
      correlated with the amount of calcium deposited. These data demonstrate that SUSI
      has utility as a noninvasive imaging method for quantitative analysis of
      mineralization in 3D protein constructs. Such techniques may assist the
      development of engineered orthopedic tissues.

PMID- 22624792
TI  - Lethal necrosis and perforation of the stomach and the aorta after multiple EUS
      guided celiac plexus neurolysis procedures in a patient with chronic
      pancreatitis.

PMID- 22624793
TI  - Multisociety sedation curriculum for gastrointestinal endoscopy.

PMID- 22624795
TI  - Immune reconstitution uveitis complicated by vitreoretinal traction and formation
      of a retinal tear.
AB  - The authors report a case of immune reconstitution uveitis induced by
      cytomegalovirus retinitis with subsequent development of vitreoretinal traction
      and a resultant retinal tear.

PMID- 22624796
TI  - Successful management of choroidal metastasis with intravitreal ranibizumab
      injections.
AB  - Uveal metastases are the most frequent intraocular malignancy in adults. Among
      various treatment modalities, previous studies have described intravitreal
      injections of bevacizumab to suppress tumor vascularity. Because of its smaller
      molecular size, compared to bevacizumab, ranibizumab may offer better tissue
      penetration and be more efficient in suppressing neovascularization in choroidal
      lesions. This report presents two cases of choroidal metastases from bronchial
      and nasopharyngeal carcinoma that were treated as a series of three intravitreal
      ranibizumab injections (0.5 mg each), showing definite signs of regression. The
      encouraging results imply that intravitreal ranibizumab may be effective in the
      management of choroidal metastases, but this finding will have to be confirmed by
      larger prospective studies.

PMID- 22624794
TI  - Reduced glutamate decarboxylase 65 protein within primary auditory cortex
      inhibitory boutons in schizophrenia.
AB  - BACKGROUND: Schizophrenia is associated with perceptual and physiological
      auditory processing impairments that may result from primary auditory cortex
      excitatory and inhibitory circuit pathology. High-frequency oscillations are
      important for auditory function and are often reported to be disrupted in
      schizophrenia. These oscillations may, in part, depend on upregulation of gamma
      aminobutyric acid synthesis by glutamate decarboxylase 65 (GAD65) in response to
      high interneuron firing rates. It is not known whether levels of GAD65 protein or
      GAD65-expressing boutons are altered in schizophrenia. METHODS: We studied two
      cohorts of subjects with schizophrenia and matched control subjects, comprising
      27 pairs of subjects. Relative fluorescence intensity, density, volume, and
      number of GAD65-immunoreactive boutons in primary auditory cortex were measured
      using quantitative confocal microscopy and stereologic sampling methods. Bouton
      fluorescence intensities were used to compare the relative expression of GAD65
      protein within boutons between diagnostic groups. Additionally, we assessed the
      correlation between previously measured dendritic spine densities and GAD65
      immunoreactive bouton fluorescence intensities. RESULTS: GAD65-immunoreactive
      bouton fluorescence intensity was reduced by 40% in subjects with schizophrenia
      and was correlated with previously measured reduced spine density. The reduction
      was greater in subjects who were not living independently at time of death. In
      contrast, GAD65-immunoreactive bouton density and number were not altered in deep
      layer 3 of primary auditory cortex of subjects with schizophrenia. CONCLUSIONS:
      Decreased expression of GAD65 protein within inhibitory boutons could contribute
      to auditory impairments in schizophrenia. The correlated reductions in dendritic
      spines and GAD65 protein suggest a relationship between inhibitory and excitatory
      synapse pathology in primary auditory cortex.

PMID- 22624797
TI  - Social behavior in mild cognitive impairment and early dementia.
AB  - Social behavioral abnormalities are commonly seen in the later stages of
      dementia. However, there has been only limited empirical study of social
      functioning in the earlier stages of the disease, or in individuals diagnosed
      with mild cognitive impairment (MCI). The aim of the present study was to test
      whether these clinical groups show more socially inappropriate and prejudicial
      behavior relative to controls, as rated by informants. No group differences were
      identified for ratings of either socially appropriate behavior or stereotyping
      and prejudice. However, the results also indicated that informants rated
      participants with dementia as showing the most inappropriate behavior, and that
      these ratings were related to participants' degree of immediate logical memory
      impairment, but not to delayed memory recall or to more general neurocognitive
      decline as indexed by the Mini Mental State Examination. Together, these results
      have implications for an understanding of some of the changes in social function
      seen in abnormal adult aging.

PMID- 22624798
TI  - Ex vivo detection of iron oxide magnetic nanoparticles in mice using their
      intrinsic peroxidase-mimicking activity.
AB  - Iron oxide magnetic nanoparticles (MNPs) are widely used as diagnostic and
      therapeutic agents for biomedical applications. Quantitatively analyzing
      biodistribution, pharmacokinetics and organ clearance of MNPs in mouse models is
      important for understanding their in vivo behavior. In this study, we developed a
      novel histochemical method for visualizing unlabeled MNPs in mouse tissues by
      employing their intrinsic peroxidase-mimicking activity, regarding which we
      reported previously that MNPs could catalyze the oxidation of peroxidase
      substrates to produce a color reaction at the site of MNPs (Gao et al. Nat.
      Nanotechnol.2007, 2, 577-583). Based on this MNPs-peroxidase approach, we
      determined the biodistribution and organ clearance of MNPs by visualizing and
      quantifying the localization of MNPs within the main organs. Compared to
      traditional Prussian blue assay, this novel MNPs-peroxidase approach has higher
      sensitivity. In conclusion, the developed MNPs-peroxidase approach based on
      intrinsic peroxidase activity of iron oxide nanoparticles was used effectively
      for quantitative detection of MNPs in mice by histochemical staining. Presumably,
      other nanoparticles having intrinsic peroxidase activity could also be
      considered.

PMID- 22624799
TI  - Plant-driven weathering of apatite--the role of an ectomycorrhizal fungus.
AB  - Ectomycorrhizal (EcM) fungi are increasingly recognized as important agents of
      mineral weathering and soil development, with far-reaching impacts on
      biogeochemical cycles. Because EcM fungi live in a symbiotic relationship with
      trees and in close contact with bacteria and archaea, it is difficult to
      distinguish between the weathering effects of the fungus, host tree and other
      micro-organisms. Here, we quantified mineral weathering by the fungus Paxillus
      involutus, growing in symbiosis with Pinus sylvestris under sterile conditions.
      The mycorrhizal trees were grown in specially designed sterile microcosms in
      which the supply of soluble phosphorus (P) in the bulk media was varied and
      grains of the calcium phosphate mineral apatite mixed with quartz, or quartz
      alone, were provided in plastic wells that were only accessed by their fungal
      partner. Under P limitation, pulse labelling of plants with (14)CO(2) revealed
      plant-to-fungus allocation of photosynthates, with 17 times more (14)C
      transferred into the apatite wells compared with wells with only quartz. Fungal
      colonization increased the release of P from apatite by almost a factor of three,
      from 7.5 (+/-1.1) * 10(-10) mol m(-2) s(-1) to 2.2 (+/-0.52) * 10(-9) mol m(-2)
      s(-1). On increasing the P supply in the microcosms from no added P, through
      apatite alone, to both apatite and orthophosphate, the proportion of biomass in
      roots progressively increased at the expense of the fungus. These three
      observations, (i) proportionately more plant energy investment in the fungal
      partner under P limitation, (ii) preferential fungal transport of photosynthate
      derived carbon towards patches of apatite grains and (iii) fungal enhancement of
      weathering rate, reveal the tightly coupled plant-fungal interactions
      underpinning enhanced EcM weathering of apatite and its utilization as P source.

PMID- 22624800
TI  - The good-old-days bias and post-concussion syndrome symptom reporting in a non
      clinical sample.
AB  - PRIMARY OBJECTIVE: To investigate the good-old-days bias, a psychosocial factor
      associated with post-concussion syndrome (PCS). STUDY DESIGN: Repeated measures
      comparison of PCS symptoms reported 6 months prior (retrospectively) and
      currently. A non-clinical sample was used to determine if this bias is a general
      recall bias. METHODS AND PROCEDURES: Fifty-seven university students with no
      history of brain injury or neurological disease completed the British Columbia
      Post-concussion Symptom Inventory. Symptoms were reported on two occasions,
      spaced 1 week apart, commencing with current symptoms. MAIN OUTCOMES AND RESULTS:
      Using PCS symptom frequency by severity product scores, there was no significant
      difference in the 13 PCS symptoms reported across occasions, nor the relevant
      summary score (p = 0.199). These data do not support the presence of a general
      recall bias. However, significant differences emerged when analysed using a
      simple count of the total number of endorsed symptoms (p = 0.002, d = 0.39, small
      to-medium effect) or the sample percentage that endorsed each symptom (four
      symptoms were endorsed by fewer participants retrospectively than currently).
      CONCLUSIONS: There is only weak evidence of a general recall bias in this non
      clinical sample. Further consideration of the methods used to study this bias and
      its role clinically is needed.

PMID- 22624801
TI  - Rhodium-catalyzed intermolecular amidation of arenes with sulfonyl azides via
      chelation-assisted C-H bond activation.
AB  - We report the direct amidation of arene C-H bonds using sulfonyl azides as the
      amino source to release N(2) as the single byproduct. The reaction is catalyzed
      by a cationic rhodium complex under external oxidant-free conditions in the
      atmospheric environment. A broad range of chelate group-containing arenes are
      selectively amidated with excellent functional group tolerance, thus opening a
      new avenue to practical intermolecular C-N bond formation.

PMID- 22624802
TI  - Successful ABO-incompatible kidney transplantation in patient with congenital
      afibrinogenemia.

PMID- 22624804
TI  - How may the transition to value-based payment influence gastroenterology: threat
      or opportunity?

PMID- 22624805
TI  - Inclusion bodies as potential vehicles for recombinant protein delivery into
      epithelial cells.
AB  - BACKGROUND: We present the potential of inclusion bodies (IBs) as a protein
      delivery method for polymeric filamentous proteins. We used as cell factory a
      strain of E. coli, a conventional host organism, and keratin 14 (K14) as an
      example of a complex protein. Keratins build the intermediate filament
      cytoskeleton of all epithelial cells. In order to build filaments, monomeric K14
      needs first to dimerize with its binding partner (keratin 5, K5), which is then
      followed by heterodimer assembly into filaments. RESULTS: K14 IBs were
      electroporated into SW13 cells grown in culture together with a "reporter"
      plasmid containing EYFP labeled keratin 5 (K5) cDNA. As SW13 cells do not
      normally express keratins, and keratin filaments are built exclusively of keratin
      heterodimers (i.e. K5/K14), the short filamentous structures we obtained in this
      study can only be the result of: a) if both IBs and plasmid DNA are transfected
      simultaneously into the cell(s); b) once inside the cells, K14 protein is being
      released from IBs; c) released K14 is functional, able to form heterodimers with
      EYFP-K5. CONCLUSIONS: Soluble IBs may be also developed for complex cytoskeletal
      proteins and used as nanoparticles for their delivery into epithelial cells.

PMID- 22624806
TI  - Urinary metabolite variation is associated with pathological progression of the
      post-hepatitis B cirrhosis patients.
AB  - Cirrhosis is a common and terminal outcome of many chronic liver conditions. A
      urinary metabonomic study using gas chromatography-mass spectrometry (GC-MS) and
      ultra performance liquid chromatography time-of-flight mass spectrometry (UPLC
      TOFMS) was carried out to elucidate the pathophysiological basis of posthepatitis
      B cirrhosis in 63 posthepatitis B cirrhosis patients and 31 health controls.
      Urinary metabolic profile and corresponding differential metabolites associated
      with Child-Pugh (CP) grading of liver function were characterized, in addition to
      the blood routine, liver, and renal function tests. Multivariate statistical
      tools including principal component analysis (PCA) and orthogonal partial least
      squares-discriminant analysis (OPLS-DA) were employed in the metabolite analysis
      along with a univariate statistical method, Wilcoxon-Mann-Whitney test. The
      alterations of differential metabolites contributing to the intergroup variation
      between healthy controls and cirrhotic patients, and among cirrhosis of CP grade
      A, B and C were also investigated. Six metabolites, alpha-hydroxyhippurate,
      tyrosine-betaxanthin, 3-hydroxyisovalerate, canavaninosuccinate, estrone, and
      glycoursodeoxycholate, were significantly altered among cirrhotic patients with
      CP A, B, and C, reflecting abnormal metabolism of amino acid, bile acids,
      hormones, and intestinal microbial metabolism. The results show that dynamic
      alteration of urinary metabolome, characterized by the changes of a panel of the
      differential metabolite markers, is indicative of an exacerbated liver function,
      highlighting their diagnostic and prognostic potential for the liver cirrhosis
      development.

PMID- 22624807
TI  - Appropriate use of GI endoscopy.

PMID- 22624808
TI  - The role of endoscopy in the management of acute non-variceal upper GI bleeding.

PMID- 22624809
TI  - Reliability measures in managing GI bleeding.
AB  - BACKGROUND: Multiple procedures and devices are used in a complex interplay to
      diagnose and treat GI bleeding. OBJECTIVE: To model how a large variety of
      diagnostic and therapeutic components interact in the successful management of GI
      bleeding. DESIGN: The analysis uses the concept of reliability block diagrams
      from probability theory to model management outcome. Separate components of the
      management process are arranged in a serial or parallel fashion. If the outcome
      depends on the function of each component individually, such components are
      modeled to be arranged in series. If components complement each other and can
      mutually compensate for each of their failures, such components are arranged in a
      parallel fashion. SETTING: General endoscopy practice. PATIENTS: Patients with GI
      bleeding of unknown etiology. INTERVENTIONS: All available endoscopic and
      radiographic means to diagnose and treat GI bleeding. MAIN OUTCOME MEASUREMENTS:
      Process reliability in achieving hemostasis. RESULTS: Serial arrangements tend to
      reduce process reliability, whereas parallel arrangements increase it. Whenever
      possible, serial components should be bridged and complemented by additional
      alternative (parallel) routes of operation. Parallel components with low
      individual reliability can still contribute to overall process reliability as
      long as they function independently of other pre-existing alternatives.
      LIMITATIONS: Probability of success associated with individual components is
      partly unknown. CONCLUSIONS: Modeling management of GI bleeding by a reliability
      block diagram provides a useful tool in assessing the impact of individual
      endoscopic techniques and administrative structures on the overall outcome.

PMID- 22624810
TI  - Duodenal bulb biopsies for diagnosing adult celiac disease: is there an optimal
      biopsy site?
AB  - BACKGROUND: Recent studies highlight the role of duodenal bulb biopsy in the
      diagnosis of celiac disease. OBJECTIVE: To determine whether a targeted duodenal
      bulb biopsy in addition to distal duodenal biopsies is the optimal strategy to
      identify villous atrophy. DESIGN: Prospective cohort study. SETTING: Tertiary
      care referral center. PATIENTS: Seventy-seven patients undergoing clinically
      indicated EGD with duodenal biopsies were recruited. Of these, 28 had newly
      diagnosed celiac disease and 49 were controls. INTERVENTIONS: At endoscopy, 8
      duodenal biopsy specimens were taken: 4 from the second part of the duodenum and
      4 quadrantically from the bulb (at the 3-, 6-, 9-, and 12-o'clock positions).
      MAIN OUTCOME MEASUREMENTS: Increasing the diagnostic yield and detection of the
      most severe villous atrophy in celiac disease with the addition of a targeted
      duodenal bulb biopsy. RESULTS: The most severe degree of villous atrophy was
      detected when distal duodenal biopsy specimens were taken in addition to a
      duodenal bulb biopsy specimen from either the 9- or 12-o'clock position (96.4%
      sensitivity; 95% CI, 79.7%-100%). The difference between the 12-o'clock position
      biopsy and the 3-o'clock position biopsy in detecting the most severe villous
      atrophy was 92% (24/26) versus 65% (17/26) (P = .02). LIMITATIONS: Small sample
      and study performed in a tertiary referral center. CONCLUSIONS: This study
      demonstrates the patchy appearance of villous atrophy that occurs within the
      duodenum. A targeted duodenal bulb biopsy from either the 9- or 12-o'clock
      position in addition to distal duodenal biopsies may improve diagnostic yields by
      detecting the most severe villous atrophy within the duodenum.

PMID- 22624811
TI  - What are we missing when colon preparation is inadequate?

PMID- 22624812
TI  - Colonoscopy quality, quality measures, and a natural language processing tool for
      electronic health records.

PMID- 22624813
TI  - History of portal hypertension and endoscopic treatment of esophageal varices.

PMID- 22624814
TI  - Novel technique of endoscopic submucosal dissection by using external forceps for
      early rectal cancer (with videos).
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is more difficult for rectal
      cancer than for gastric cancer. OBJECTIVE: To evaluate the feasibility and safety
      of an ESD procedure by using external forceps for early rectal cancer. DESIGN: A
      case series. SETTING: A tertiary medical center. PATIENTS: Thirteen patients with
      early-stage rectal cancer were enrolled. Twelve of the 13 lesions were granular
      type laterally spreading tumors and 1 was a protruding tumor. INTERVENTIONS:
      After circumferential incision around the lesion with a dual-knife or a flex
      knife, bendable external forceps were introduced with the help of grasping
      forceps inserted through the accessory channel and anchored at the anal margin of
      the lesion. After the forceps were bent, they were locked. With gentle anal
      traction and bending applied with the forceps, the lesion was elevated, the
      submucosal layer was opened, and the submucosal layer was dissected from the
      grasped side, facilitating dissection of the submucosal layer under direct
      vision. MAIN OUTCOME MEASUREMENTS: Technical success, complication rates.
      RESULTS: The mean lesion size was 33.0 mm (range 20-80 mm), and the mean
      operating time was 60 minutes (range 20-150 minutes). All lesions could be
      resected en bloc with tumor-free margins. Major bleeding after ESD occurred in
      only 1 patient (7.7%), who did not require blood transfusion. Perforation did not
      occur in any patient. LIMITATIONS: Single-center experience, small number of
      patients. CONCLUSION: This ESD procedure using external forceps for early-stage
      rectal cancers is feasible and safe.

PMID- 22624815
TI  - Novel approach to therapeutic ERCP after long-limb Roux-en-Y gastric bypass
      surgery using transgastric self-expandable metal stents: experimental outcomes
      and first human case study (with videos).
AB  - BACKGROUND: ERCP in Roux-en-Y gastric bypass (RYGB) patients is challenging.
      Balloon-assisted enteroscopy (BAE) allows access to the excluded stomach with
      creation of a percutaneous endoscopic gastrostomy (PEG). Transgastric self
      expandable metal stent (SEMS) placement may allow antegrade ERCP in 1 session.
      OBJECTIVE: To determine the feasibility of transgastric endoscopy and ERCP
      through a newly created PEG augmented by SEMS placement. DESIGN: Prospective live
      animal study; human case report. SETTINGS: Animal laboratory and endoscopy units,
      tertiary care medical center. SUBJECTS: Nine domestic pigs; 1 patient.
      INTERVENTIONS: PEG tract with SEMS placement; transgastric endoscopy through
      SEMS. MAIN OUTCOME MEASUREMENTS: Technical success, feasibility of transgastric
      endoscopy. RESULTS: Successful SEMS deployment was achieved in 9 of 9 animals.
      The stent was removed in 6 animals; 3 were killed within 24 hours (group A) and 3
      were killed 1 week later (group B). In 3 animals, stents remained in place, they
      were killed 9 to 15 days later (group C). Duodenoscopy was difficult in 1 animal
      from group A resulting in stent dislodgment. Peristomal infection occurred in 1
      animal in group B. In group C, 1 stent was buried subcutaneously and 1 completely
      migrated out. Necropsy showed no peritoneal fluid or peritonitis in any animal.
      In the 1 patient, BAE-assisted PEG and SEMS placement in the excluded stomach
      allowed antegrade ERCP and biliary sphincterotomy without adverse events.
      LIMITATIONS: Small number of subjects. CONCLUSIONS: Performance of PEG with
      immediate SEMS placement allows for antegrade transgastric ERCP during 1
      procedure. With the use of BAE, retrograde PEG/SEMS in excluded stomach allows
      therapeutic ERCP without need for surgery.

PMID- 22624816
TI  - Sensitivity analysis, not a calculation of sensitivity, is essential in a
      propensity score analysis.

PMID- 22624818
TI  - Endoscopic management of colonoscopic perforations.

PMID- 22624819
TI  - Systemic candidiasis arising from percutaneous endoscopic gastrostomy tube.

PMID- 22624820
TI  - Endoscopic hemoclip placement and endoscopic band ligation for Dieulafoy's
      lesions.

PMID- 22624823
TI  - Asymptomatic transmission of Treponema pallidum (syphilis) through deceased donor
      liver transplantation.
AB  - A 55-year-old woman underwent liver transplantation (LT) with a graft from a
      deceased donor. Mandatory pre-donation investigations showed positive syphilis
      serology that was available only after the transplant, with high Treponema
      pallidum particle agglutination assay titer compatible with donor syphilis
      infection. Despite the institution of appropriate post-exposure prophylaxis, the
      recipient demonstrated latent seroconversion; however, liver graft function
      improved without evidence of syphilitic hepatitis or other manifestations of the
      disease. Through this first reported case of asymptomatic transmission of
      syphilis following LT, we highlight the investigations and treatment strategies
      for donor-derived syphilis in liver transplant recipients. This report
      supplements the existing limited evidence on safe use of infected grafts from
      syphilitic donors through appropriate post-exposure prophylaxis.

PMID- 22624822
TI  - Histamine H4 receptor antagonists as potent modulators of mammalian vestibular
      primary neuron excitability.
AB  - BACKGROUND AND PURPOSE: Betahistine, the main histamine drug prescribed to treat
      vestibular disorders, is a histamine H(3) receptor antagonist. Here, we explored
      the potential for modulation of the most recently cloned histamine receptor (H(4)
      receptor) to influence vestibular system function, using a selective H(4)
      receptor antagonist JNJ 7777120 and the derivate compound JNJ 10191584.
      EXPERIMENTAL APPROACH: RT-PCR was used to assess the presence of H(4) receptors
      in rat primary vestibular neurons. In vitro electrophysiological recordings and
      in vivo behavioural approaches using specific antagonists were employed to
      examine the effect of H(4) receptor modulation in the rat vestibular system. KEY
      RESULTS: The transcripts of H(4) and H(3) receptors were present in rat
      vestibular ganglia. Application of betahistine inhibited the evoked action
      potential firing starting at micromolar range, accompanied by subsequent strong
      neuronal depolarization at higher concentrations. Conversely, reversible
      inhibitory effects elicited by JNJ 10191584 and JNJ 7777120 began in the
      nanomolar range, without inducing neuronal depolarization. This effect was
      reversed by application of the selective H(4) receptor agonist 4-methylhistamine.
      Thioperamide, a H(3) /H(4) receptor antagonist, exerted effects similar to those
      of H(3) and H(4) receptor antagonists, namely inhibition of firing at nanomolar
      range and membrane depolarization above 100 uM. H(4) receptor antagonists
      significantly alleviated the vestibular deficits induced in rats, while neither
      betahistine nor thioperamide had significant effects. CONCLUSIONS AND
      IMPLICATIONS: H(4) receptor antagonists have a pronounced inhibitory effect on
      vestibular neuron activity. This result highlights the potential role of H(4)
      receptors as pharmacological targets for the treatment of vestibular disorders.

PMID- 22624824
TI  - Nature and the natural environment as health facilitators: the need to
      reconceptualize the ICF environmental factors.
AB  - PURPOSE: This work examines the environmental factors component of the
      International Classification of Functioning, Disability, and Health (ICF)
      relative to current health-facilitating evidence about natural environmental
      factors. We argue that the environmental factors component warrants
      reconceptualization in order to offer an extended and more systematic framework
      for identifying and measuring health-facilitating natural environmental factors.
      METHOD: Current evidence highlighting the potential health-facilitating benefits
      of natural environmental factors is synthesized and considered in the context of
      the ICF framework and its coding system. RESULTS: In its current form, the ICF's
      conceptual framework and coding system are inadequate for identifying and
      measuring natural environmental factors in individuals and groups with and/or
      without health conditions. CONCLUSION: The ICF provides an advanced framework for
      health and disability that reflects contemporary conceptualizations about health.
      However, given the scope of emerging evidence highlighting positive health and
      well-being outcomes associated with natural environmental factors, we believe the
      environmental factors component requires further advancement to reflect this
      current knowledge. Reconceptualizing the environmental factors component supports
      a more holistic interpretation of the continuum of environmental factors as both
      facilitators and barriers. In doing so, it strengthens the ICF's utility in
      identifying and measuring health-facilitating natural environmental factors.

PMID- 22624825
TI  - Potential roles of stem cells in the management of sensorineural hearing loss.
AB  - BACKGROUND: In the management of sensorineural hearing loss, effective therapy
      for degenerated hair cells, third order neurons, ganglions, dendrites and
      synaptic areas of the vestibulo-cochleo-cerebral pathway remains an enigma.
      Transplantation of stem and progenitor cells appears to be an emerging potential
      solution, and is the focus of this review. AIM: To review recent developments in
      the management of sensorineural hearing loss in the field of stem cell research.
      MATERIALS AND METHOD: A systematic review of the English language literature
      included all experimental and non-experimental studies with a Jadad score of
      three or more, published between 2000 and 2010 and included in the following
      databases: Cochrane Library Ear, Nose and Throat Disorders; Medline; Google
      Scholar; Hinari; and the Online Library of Toronto University. RESULTS: Of the
      455 and 29 600 articles identified from Medline and Google Scholar, respectively,
      48 met the inclusion criteria. These were independently reviewed and jointly
      analysed. CONCLUSION: Although there is not yet any evidence from successful
      human studies, stem cell and 'alternative stem cell' technology seems to
      represent the future of sensorineural hearing loss management.

PMID- 22624826
TI  - Living through gynaecological cancer: three typologies.
AB  - AIMS AND OBJECTIVES: The aim of this qualitative study is to highlight how women
      experienced living through gynaecological cancer. BACKGROUND: The increasing
      number of long-term survivors after cancer has created a greater need for
      knowledge about how patients live through the illness. DESIGN: A qualitative
      design, with a phenomenological-hermeneutical perspective, provided the framework
      for the study. METHOD: Thirty-two unstructured in-depth interviews with 16 women
      were conducted. Each woman was interviewed twice: one year apart, and five and
      six years after treatment, respectively. Stepwise meaning condensation was used
      to analyse the data. RESULTS: Based on the women's first-hand stories about their
      experiences with cancer, we identified three typologies, describing different
      ways in which the women negotiated encountering and living through cancer. These
      typologies are the emotion- and relationship-oriented women, the activity
      oriented women and the self-controlled women. CONCLUSIONS: There are substantial
      differences regarding how women process the experience of cancer. The findings
      add valuable knowledge about the impact cancer can have on women's lives and can
      be of help for nurses who support patients during treatment and follow-up.
      RELEVANCE TO CLINICAL PRACTICE: Understanding different ways women can experience
      living through cancer is fundamental for the development and improvement of
      cancer care. Allowing time for the women to talk with nurses about their cancer
      experiences could be essential during treatment and follow-up. Nurses can support
      the women by listening to their stories, accepting their emotions and informing
      them in detail. The findings in this study imply that strengthening nurses'
      listening and conversational competence can be of importance for supporting
      patients after cancer. By building on the women's own stories, it might be
      possible to create a follow-up process that is individually tailored for each
      cancer patient.

PMID- 22624827
TI  - Patch testing with the textile dyes Disperse Orange 1 and Disperse Yellow 3 and
      some of their potential metabolites, and simultaneous reactions to para-amino
      compounds.
AB  - BACKGROUND: It is known that, in vitro, human skin bacteria are able to split
      disperse azo dyes into the corresponding aromatic amines, some of which are
      sensitizers in the local lymph node assay. We hypothesize that the molecules of
      disperse dyes migrate onto the skin while garments are worn, and are metabolized
      and degraded by commensal skin bacteria. These molecules penetrate the skin and
      induce sensitization. OBJECTIVES: To evaluate the elicitation capacities of the
      possible azo-degradation products of the selected azo disperse dyes in patients
      allergic to them and to compare it with the elicitation capacities of other para
      compounds. METHODS: Ten patients allergic to Disperse Yellow 3 (DY3) and/or
      Disperse Orange 1 (DO1) were patch tested with a dilution series of the purified
      dyes 4-nitroaniline and p-aminodiphenylamine in concentrations equimolar to those
      of purified DO1 in the dilution series, as well as 4-aminoacetanilide and 2-amino
      p-cresol in concentrations equimolar to those of purified DY3 in the dilution
      series. Results. Three patterns of patch test reactions could be seen. The 6
      patients who were positive to DO1 and DY3 also reacted to p-aminodiphenylamine
      and 2-amino-p-cresol. Two patients were positive to DO1 only, and both reacted to
      p-aminodiphenylamine, but to neither 4-aminoacetanilide or 2-amino-p-cresol. Two
      patients did not react to DO1 or DY3 on this occasion. CONCLUSION: We show that
      it is possible that the major sensitizers in contact allergy to DO1 and DY3 are
      their metabolites, p-aminodiphenylamine and 2-amino-p-cresol, respectively, which
      might be formed by the azoreductase pathway of skin bacteria.

PMID- 22624828
TI  - Test-retest reliability of the Danish Adult Reading Test in patients with
      comorbid psychosis and cannabis-use disorder.
AB  - BACKGROUND: The New Adult Reading Test is a common instrument for assessing pre
      morbid IQ for patients with, for instance, schizophrenia. However, test-retest
      reliability has not been established for patients dually diagnosed with psychosis
      and substance use disorder. Furthermore, test-retest reliability of the Danish
      adaptation has never been established in any population. AIMS: To determine the
      test-retest reliability of the Danish Adult Reading Test (DART) (adapted from the
      National Adult Reading Test, NART) for patients dually diagnosed with psychosis
      and cannabis-use disorder. METHODS: This was a secondary analysis of the CapOpus
      randomized trial. As part of the trial, 103 patients were randomized, and
      completed the DART up to three times. Pearson's r and pairwise t-tests were
      calculated. RESULTS: DART score was independent of randomization, cannabis-use
      frequency and psychopathology. Scores at the last interview were slightly higher
      than at the first two. Correlation over time was very strong (0.8 < r <0.9) for
      all pairwise comparisons of interviews. Variations in DART scores and estimated
      pre-morbid IQ over time were sometimes of borderline statistical significance but
      not of clinical relevance. CONCLUSIONS: DART and NART have high test-retest
      reliability, but apparently non-systematic, clinically irrelevant variation over
      time does occur. CLINICAL IMPLICATION: The Danish adaptation of the New Adult
      Reading Test possesses good test-retest reliability, making it an appropriate
      choice for assessment of pre-morbid IQ, and in patients with dually diagnosed
      psychosis and cannabis-use disorder.

PMID- 22624830
TI  - Isolated extrahepatic bile duct rupture: a rare consequence of blunt abdominal
      trauma. Case report and review of the literature.
AB  - A 16-year-old girl suffered blunt abdominal trauma. Clinically, a severe motor
      impairment with paraesthesia of the legs was found. Posterior osteosynthesis in
      T10-L1 with laminectomy in T10-T12 and posterolateral arthrodesis in T11-T12 was
      performed because of a dorsal traumatic vertebral fracture. On hospital day 7,
      because of an acute abdomen, surgical laparoscopic exploration showed sterile
      bloody fluid without any evident hemorrhagic injury. On hospital day 11, the
      patient was reoperated on by the laparoscopic approach for increasing abdominal
      pain and fever: a peritoneal biliary fluid was aspirated. After conversion to
      open surgery, cholecystectomy was performed. Intraoperative cholangiography was
      considered as normal. On arrival at our institution 13 days after injury, the
      patient was operated on for a biliary peritonitis. Intraoperatively, a trans
      cystic cholangiography showed a biliary leakage of the common bile duct; a T-tube
      was placed into the common bile duct; a subhepatic drainage was placed too. On
      postoperative day 30, a T-tube cholangiography showed a normal biliary tree,
      without any leakage, and the T-tube was subsequently removed. The patient had a
      complete recovery.

PMID- 22624829
TI  - Multi-locus variable number tandem repeat analysis of 7th pandemic Vibrio
      cholerae.
AB  - BACKGROUND: Seven pandemics of cholera have been recorded since 1817, with the
      current and ongoing pandemic affecting almost every continent. Cholera remains
      endemic in developing countries and is still a significant public health issue.
      In this study we use multilocus variable number of tandem repeats (VNTRs)
      analysis (MLVA) to discriminate between isolates of the 7th pandemic clone of
      Vibrio cholerae. RESULTS: MLVA of six VNTRs selected from previously published
      data distinguished 66 V. cholerae isolates collected between 1961-1999 into 60
      unique MLVA profiles. Only 4 MLVA profiles consisted of more than 2 isolates. The
      discriminatory power was 0.995. Phylogenetic analysis showed that, except for the
      closely related profiles, the relationships derived from MLVA profiles were in
      conflict with that inferred from Single Nucleotide Polymorphism (SNP) typing. The
      six SNP groups share consensus VNTR patterns and two SNP groups contained
      isolates which differed by only one VNTR locus. CONCLUSIONS: MLVA is highly
      discriminatory in differentiating 7th pandemic V. cholerae isolates and MLVA data
      was most useful in resolving the genetic relationships among isolates within
      groups previously defined by SNPs. Thus MLVA is best used in conjunction with SNP
      typing in order to best determine the evolutionary relationships among the 7th
      pandemic V. cholerae isolates and for longer term epidemiological typing.

PMID- 22624831
TI  - Concentration measurements of bubbles in a water column using an optical
      tomography system.
AB  - Optical tomography provides a means for the determination of the spatial
      distribution of materials with different optical density in a volume by non
      intrusive means. This paper presents results of concentration measurements of gas
      bubbles in a water column using an optical tomography system. A hydraulic flow
      rig is used to generate vertical air-water two-phase flows with controllable
      bubble flow rate. Two approaches are investigated. The first aims to obtain an
      average gas concentration at the measurement section, the second aims to obtain a
      gas distribution profile by using tomographic imaging. A hybrid back-projection
      algorithm is used to calculate concentration profiles from measured sensor values
      to provide a tomographic image of the measurement cross-section. The algorithm
      combines the characteristic of an optical sensor as a hard field sensor and the
      linear back projection algorithm.

PMID- 22624832
TI  - Cyclic guanosine monophosphate signaling and phosphodiesterase-5 inhibitors in
      cardioprotection.
AB  - Cyclic guanosine monophosphate (cGMP) is an important intracellular second
      messenger that mediates multiple tissue and cellular responses. The cGMP pathway
      is a key element in the pathophysiology of the heart and its modulation by drugs
      such as phosphodiesterase (PDE)-5 inhibitors and guanylate cyclase activators may
      represent a promising therapeutic approach for acute myocardial infarction,
      cardiac hypertrophy, heart failure, and doxorubicin cardiotoxicity in patients.
      In addition, PDE-5 inhibitors may prove to be innovative therapeutic agents for
      enhancing the chemosensitivity of doxorubicin while providing concurrent cardiac
      benefit.

PMID- 22624833
TI  - Influence of genetic polymorphisms on the effect of high- and standard-dose
      clopidogrel after percutaneous coronary intervention: the GIFT (Genotype
      Information and Functional Testing) study.
AB  - OBJECTIVES: This study sought to evaluate the influence of single nucleotide
      polymorphisms (SNPs) on the pharmacodynamic effect of high- or standard-dose
      clopidogrel after percutaneous coronary intervention (PCI). BACKGROUND: There is
      a lack of prospective, multicenter data regarding the effect of different genetic
      variants on clopidogrel pharmacodynamics over time in patients undergoing PCI.
      METHODS: The GRAVITAS (Gauging Responsiveness with A VerifyNow assay-Impact on
      Thrombosis And Safety) trial screened patients with platelet function testing
      after PCI and randomly assigned those with high on-treatment reactivity (OTR) to
      either high- or standard-dose clopidogrel; a cohort of patients without high OTR
      were also followed. DNA samples obtained from 1,028 patients were genotyped for
      41 SNPs in 17 genes related to platelet reactivity. After adjusting for clinical
      characteristics, the associations between the SNPs and OTR using linear
      regression were evaluated. RESULTS: CYP2C19*2 was significantly associated with
      OTR at 12 to 24 h (R(2) = 0.07, p = 2.2 * 10(-15)), 30 days (R(2) = 0.10, p = 1.3
      * 10(-7)), and 6 months after PCI (R(2) = 0.07, p = 1.9 * 10(-11)), whereas PON1,
      ABCB1 3435 C->T, and other candidate SNPs were not. Carriers of 1 and 2 reduced
      function CYP2C19 alleles were significantly more likely to display persistently
      high OTR at 30 days and 6 months, irrespective of treatment assignment. The
      portion of the risk of persistently high OTR at 30 days attributable to reduced
      function CYP2C19 allele carriage was 5.2% in the patients randomly assigned to
      high-dose clopidogrel. CONCLUSIONS: CYP2C19, but not PON1 or ABCB1, is a
      significant determinant of the pharmacodynamic effects of clopidogrel, both early
      and late after PCI. In patients with high OTR identified by platelet function
      testing, the CYP2C19 genotype provides limited incremental information regarding
      the risk of persistently high reactivity with clopidogrel 150-mg maintenance
      dosing. (Genotype Information and Functional Testing Study [GIFT]; NCT00992420).

PMID- 22624834
TI  - Dynamicity of the J-wave in idiopathic ventricular fibrillation with a special
      reference to pause-dependent augmentation of the J-wave.
AB  - OBJECTIVES: This study evaluated the pause-dependency of the J-wave to
      characterize this phenomenon in idiopathic ventricular fibrillation (VF).
      BACKGROUND: The J-wave can be found in apparently healthy subjects and in
      patients at risk for sudden cardiac death, and risk stratification is therefore
      needed. METHODS: Forty patients with J-wave-associated idiopathic VF were studied
      for J waves with special reference concerning pause-dependent augmentation. J
      waves were defined as those >=0.1 mV above the isoelectric line and were compared
      with 76 non-VF patients of comparable age and sex. RESULTS: The J-wave was larger
      in patients with idiopathic VF than in the controls: 0.360 +/- 0.181 mV versus
      0.192 +/- 0.064 mV (p = 0.0011). J waves were augmented during storms of VF (n =
      9 [22.5%]), which was controlled by isoproterenol; they disappeared within weeks
      in 5 patients. In addition, sudden prolongation of the R-R interval was observed
      in 27 patients induced by benign arrhythmia, and 15 patients (55.6%) demonstrated
      pause-dependent augmentation (from 0.391 +/- 0.126 mV to 0.549 +/- 0.220 mV; p <
      0.0001). In the other 12 experimental subjects and in the 76 control subjects, J
      waves remained unchanged. Pause-dependent augmentation of J waves was detected in
      55.6% (sensitivity) but was specific (100%) in the patients with idiopathic VF
      with high positive (100%) and negative (86.4%) predictive values. CONCLUSIONS:
      Pause-dependent augmentation of J waves was confirmed in about one-half of the
      patients with idiopathic VF after sudden R-R prolongation. Such dynamicity of J
      waves was specific to idiopathic VF and may be used for risk stratification.

PMID- 22624836
TI  - BOLD new directions in myocardial ischemia imaging-myocardial oxygenation
      assessment by cardiac magnetic resonance.

PMID- 22624835
TI  - Myocardial oxygenation in coronary artery disease: insights from blood oxygen
      level-dependent magnetic resonance imaging at 3 tesla.
AB  - OBJECTIVES: The purpose of this study was to assess the diagnostic accuracy of
      blood oxygen-level dependent (BOLD) MRI in suspected coronary artery disease
      (CAD). BACKGROUND: By exploiting the paramagnetic properties of deoxyhemoglobin,
      BOLD magnetic resonance imaging can detect myocardial ischemia. We applied BOLD
      imaging and first-pass perfusion techniques to: 1) examine the pathophysiological
      relationship between coronary stenosis, perfusion, ventricular scar, and
      myocardial oxygenation; and 2) evaluate the diagnostic performance of BOLD
      imaging in the clinical setting. METHODS: BOLD and first-pass perfusion images
      were acquired at rest and stress (4 to 5 min intravenous adenosine, 140
      MUg/kg/min) and assessed quantitatively (using a BOLD signal intensity index
      [stress/resting signal intensity], and absolute quantification of perfusion by
      model-independent deconvolution). A BOLD signal intensity index threshold to
      identify ischemic myocardium was first determined in a derivation arm (25 CAD
      patients and 20 healthy volunteers). To determine diagnostic performance, this
      was then applied in a separate group comprising 60 patients with suspected CAD
      referred for diagnostic angiography. RESULTS: Prospective evaluation of BOLD
      imaging yielded an accuracy of 84%, a sensitivity of 92%, and a specificity of
      72% for detecting myocardial ischemia and 86%, 92%, and 72%, respectively, for
      identifying significant coronary stenosis. Segment-based analysis revealed
      evidence of dissociation between oxygenation and perfusion (r = -0.26), with a
      weaker correlation of quantitative coronary angiography with myocardial
      oxygenation (r = -0.20) than with perfusion (r = -0.40; p = 0.005 for
      difference). Hypertension increased the odds of an abnormal BOLD response, but
      diabetes mellitus, hypercholesterolemia, and the presence of ventricular scar
      were not associated with significant deoxygenation. CONCLUSIONS: BOLD imaging
      provides valuable insights into the pathophysiology of CAD; myocardial
      hypoperfusion is not necessarily commensurate with deoxygenation. In the clinical
      setting, BOLD imaging achieves favorable accuracy for identifying the anatomic
      and functional significance of CAD.

PMID- 22624838
TI  - The changing epidemiology of infective endocarditis: the paradox of prophylaxis
      in the current and future eras.

PMID- 22624837
TI  - Temporal trends in infective endocarditis in the context of prophylaxis guideline
      modifications: three successive population-based surveys.
AB  - OBJECTIVES: The goal of this study was to evaluate temporal trends in infective
      endocarditis (IE) incidence and clinical characteristics after 2002 French IE
      prophylaxis guideline modifications. BACKGROUND: There are limited data on
      changes in the epidemiology of IE since recent guidelines recommended restricting
      the indications of antibiotic prophylaxis of IE. METHODS: Three 1-year population
      based surveys were conducted in 1991, 1999, and 2008 in 3 French regions totaling
      11 million inhabitants age >=20 years. We prospectively collected IE cases from
      all medical centers and analyzed age- and sex-standardized IE annual incidence
      trends. RESULTS: Overall, 993 expert-validated IE cases were analyzed (323 in
      1991; 331 in 1999; and 339 in 2008). IE incidence remained stable over time (95%
      confidence intervals given in parentheses/brackets): 35 (31 to 39), 33 (30 to
      37), and 32 (28 to 35) cases per million in 1991, 1999, and 2008, respectively.
      Oral streptococci IE incidence did not increase either in the whole patient
      population (8.1 [6.4 to 10.1], 6.3 [4.8 to 8.1], and 6.3 [4.9 to 8.0] in 1991,
      1999, and 2008, respectively) or in patients with pre-existing native valve
      disease. The increased incidence of Staphylococcus aureus IE (5.2 [3.9 to 6.8],
      6.8 [5.3 to 8.6], and 8.2 [6.6 to 10.2]) was not significant in the whole patient
      population (p = 0.228) but was significant in the subgroup of patients without
      previously known native valve disease (1.6 [0.9 to 2.7], 3.7 [2.6 to 5.1], and
      4.1 [3.0 to 5.6]; p = 0.012). CONCLUSIONS: Scaling down antibiotic prophylaxis
      indications was not associated with an increased incidence of oral streptococcal
      IE. A focus on avoidance of S. aureus bacteremia in all patients, including those
      with no previously known valve disease, will be required to improve IE
      prevention.

PMID- 22624839
TI  - Cardioprotective effect of beta-3 adrenergic receptor agonism: role of neuronal
      nitric oxide synthase.
AB  - OBJECTIVES: The aim of this study was to determine whether activation of beta3
      adrenergic receptor (AR) and downstream signaling of nitric oxide synthase (NOS)
      isoforms protects the heart from failure and hypertrophy induced by pressure
      overload. BACKGROUND: beta3-AR and its downstream signaling pathways are
      recognized as novel modulators of heart function. Unlike beta1- and beta2-ARs,
      beta3-ARs are stimulated at high catecholamine concentrations and induce negative
      inotropic effects, serving as a "brake" to protect the heart from catecholamine
      overstimulation. METHODS: C57BL/6J and neuronal NOS (nNOS) knockout mice were
      assigned to receive transverse aortic constriction (TAC), BRL37344 (beta3
      agonist, BRL 0.1 mg/kg/h), or both. RESULTS: Three weeks of BRL treatment in wild
      type mice attenuated left ventricular dilation and systolic dysfunction, and
      partially reduced cardiac hypertrophy induced by TAC. This effect was associated
      with increased nitric oxide production and superoxide suppression. TAC decreased
      endothelial NOS (eNOS) dimerization, indicating eNOS uncoupling, which was not
      reversed by BRL treatment. However, nNOS protein expression was up-regulated 2
      fold by BRL, and the suppressive effect of BRL on superoxide generation was
      abrogated by acute nNOS inhibition. Furthermore, BRL cardioprotective effects
      were actually detrimental in nNOS(-/-) mice. CONCLUSIONS: These results are the
      first to show in vivo cardioprotective effects of beta3-AR-specific agonism in
      pressure overload hypertrophy and heart failure, and support nNOS as the primary
      downstream NOS isoform in maintaining NO and reactive oxygen species balance in
      the failing heart.

PMID- 22624840
TI  - Alterations in beta3-adrenergic cardiac innervation and nitric oxide signaling in
      heart failure.

PMID- 22624841
TI  - Severe and diffuse arterial lesions in a patient with pseudoxanthoma elasticum.

PMID- 22624842
TI  - Regression of "gray zone" exercise-induced concentric left ventricular
      hypertrophy during prescribed detraining.

PMID- 22624843
TI  - Incidental diagnosis of cor triatriatum in 2 elderly patients.

PMID- 22624844
TI  - Multidimensional effects of acculturation on English-language neuropsychological
      test performance among HIV+ Caribbean Latinas/os.
AB  - Acculturation has been linked to neuropsychological performance in several ethnic
      groups. However, research among Latina/o samples has examined primarily
      Mexicans/Mexican Americans and has not examined Latina/o clinical populations of
      Caribbean descent. This study examined associations between a multidimensional
      acculturation measure and neuropsychological performance among 82 HIV+ Caribbean
      Latina/o adults. Multivariate results showed that US acculturation significantly
      predicted 11-14% of the variance in global neuropsychological functioning, verbal
      fluency, and processing speed, whereas Latina/o acculturation predicted 6-8% of
      the variance in motor and executive function (trend level associations). Both
      linguistic and nonlinguistic cultural factors had distinct effects on
      neuropsychological performance.

PMID- 22624845
TI  - Intensity-modulated and image-guided radiation therapy for treatment of
      genitourinary carcinomas in dogs.
AB  - BACKGROUND: External beam radiation therapy can be used to treat pelvic tumors in
      dogs, but its utility is limited by lack of efficacy data and associated late
      complications. HYPOTHESIS/OBJECTIVES: The objective of this study was to assess
      local tumor control, overall survival, and toxicosis after intensity-modulated
      and image-guided radiation therapy (IM/IGRT) for treatment of genitourinary
      carcinomas (CGUC) in dogs. ANIMALS: 21 client-owned dogs. METHODS: A
      retrospective study was performed. Medical records of dogs for which there was
      intent to treat with a course of definitive-intent IM/IGRT for CGUC between 2008
      and 2011 were reviewed. Descriptive and actuarial statistics comprised the data
      analysis. RESULTS: Primary tumors were located in the prostate (10), urinary
      bladder (9), or urethra (2). The total radiation dose ranged from 54-58 Gy,
      delivered in 20 daily fractions. Grade 1 and 2 acute gastrointestinal toxicoses
      developed in 33 and 5% of dogs, respectively. Grade 1 and 2 acute genitourinary
      and grade 1 acute integumentary toxicoses were documented in 5, 5, and 20% of
      dogs, respectively. Four dogs experienced late grade 3 gastrointestinal or
      genitourinary toxicosis. The subjective response rate was 60%. The median event
      free survival was 317 days; the overall median survival time was 654 days.
      Neither local tumor control nor overall survival was statistically dependent upon
      location of the primary tumor. CONCLUSIONS AND CLINICAL IMPORTANCE: IM/IGRT is
      generally well-tolerated and provides an effective option for locoregional
      control of CGUC. As compared with previous reports in the veterinary literature,
      inclusion of IM/IGRT in multimodal treatment protocols for CGUC can result in
      superior survival times; controlled prospective evaluation is warranted.

PMID- 22624846
TI  - Single photon counting from individual nanocrystals in the infrared.
AB  - Experimental restrictions imposed on the collection and detection of shortwave
      infrared photons (SWIR) have impeded single molecule work on a large class of
      materials whose optical activity lies in the SWIR. Here we report the successful
      observation of room-temperature single nanocrystal photoluminescence at SWIR
      wavelengths using a highly efficient multielement superconducting nanowire single
      photon detector. We confirm that the photoluminescence from single lead sulfide
      nanocrystals is strongly antibunched, demonstrating the feasibility of performing
      sophisticated photon correlation experiments on individual weak SWIR emitters,
      and, more broadly, paving the way for sensitive measurements of spectral
      observables on infrared quantum systems that are incompatible with current
      detection techniques.

PMID- 22624847
TI  - Vitrified sperm banks: the new aseptic technique for human spermatozoa allows
      cryopreservation at -86  degrees C.
AB  - The vitrification technique is simple, quick, cost-effective and has showed a
      significantly stronger cryoprotective effect in contrast to conventional
      freezing. The method is based on the rapid cooling of the cell by direct
      immersion in liquid nitrogen (LN (2) ), thereby avoiding the formation of ice
      crystals, due to the lower risk of water thawing, which impairs cell function.
      The aim of this study was to evaluate the effect of storage at -86  degrees C
      compared to the conventional -196  degrees C (under LN (2) ) on essential
      parameters of the functioning of aseptically vitrified human sperm. Sperm
      motility, integrity of mitochondrial membrane potential and the rate of DNA
      fragmentation were determined. The comparison of -86  degrees C and -196  degrees
      C demonstrated no statistical difference in sperm progressive motility (73% vs.
      77%), integrity of mitochondrial membrane potential (71% vs. 74%) or DNA
      fragmentation (3.1% vs. 2.9%). In conclusion, aseptically vitrified sperm can be
      preserved at -86  degrees C; eliminating the use of LN (2)  simplifies and
      significantly reduces the costs associated with storage in sperm banks by
      decreasing the time and space needed for storage, the effort in finding stored
      samples, and by improving safety for the operator. However, for prolonged storage
      further studies are needed.

PMID- 22624848
TI  - Posttraumatic stress disorder among paramedics: exploring a new solution with
      occupational health nurses using the Ottawa Charter as a framework.
AB  - Paramedics have the highest rate of posttraumatic stress disorder (PTSD) among
      emergency service workers, higher than police or firefighters. This disorder can
      be detrimental to their personal and family lives, as well as their careers.
      Current biomedical, behavioral, and socioenvironmental interventions do not
      address paramedics' work environment, which contributes to the high rate of PTSD.
      Occupational health nurses can influence the triad of factors contributing to
      PTSD among paramedics by facilitating social support and emotional expression
      while advocating for reduced job exposure to traumatic events. This goal can be
      accomplished by using a component of the Ottawa Charter, creating a supportive
      work environment, as a framework. Occupational health nurses, together with
      management and paramedics, can facilitate a sustainable and supportive work
      environment that initiates change from within the trauma membrane of paramedics'
      workplaces to prevent PTSD.

PMID- 22624850
TI  - Prevalence of traumatic injuries to permanent dentition and its association with
      overjet in a Swiss child population.
AB  - OBJECTIVE: Dental trauma is a very common issue in dentistry and its occurrence
      has been related to many factors. The aim of this study was to evaluate the
      prevalence of traumatic dental injuries in the permanent dentition among Swiss
      children and its association with overjet. MATERIAL AND METHODS: A sample of 1900
      children aged 6-13 years was prospectively evaluated to determine the number and
      types of injuries, the influence of overjet on the risk of suffering trauma and
      the relationships between trauma, age, gender and life conditions. RESULTS: The
      observed prevalence of trauma was higher for boys, with a slight risk increase
      with age and a peak frequency at the age of 10 years. Most of the injuries
      (91.2%) involved the upper front teeth; 87.2% of all injuries were hard tissue
      injuries (enamel or dentin fractures), and 12.8% only subluxation and luxation
      injuries. Children with an overjet of 6 mm or more had a four times higher risk
      of suffering trauma, compared with those with less overjet. CONCLUSION: This
      cross-sectional study confirmed most of the results from earlier studies dealing
      with epidemiological factors of dental injuries to the permanent dentition. Of
      all the variables analysed, overjet stood out as the most significant risk
      factor: an increased overjet of 6 mm or more had a major impact on the risk of
      trauma, which would speak in favour of early orthodontic correction of an
      increased overjet to reduce the prevalence of dental trauma.

PMID- 22624849
TI  - Occurrence of Fusarium Head Blight species and Fusarium mycotoxins in winter
      wheat in the Netherlands in 2009.
AB  - Most recent information on the occurrence of Fusarium Head Blight species and
      related mycotoxins in wheat grown in the Netherlands dates from 2001. This aim of
      this study was to investigate the incidence and levels of Fusarium Head Blight
      species and Fusarium mycotoxins, as well as their possible relationships, in
      winter wheat cultivated in the Netherlands in 2009. Samples were collected from
      individual fields of 88 commercial wheat growers. Samples were collected at
      harvest from 86 fields, and 2 weeks before the expected harvest date from 21
      fields. In all, 128 samples, the levels of each of seven Fusarium Head Blight
      species and of 12 related mycotoxins were quantified. The results showed that F.
      graminearum was the most frequently observed species at harvest, followed by F.
      avenaceum and M. nivale. In the pre-harvest samples, only F. graminearum and M.
      nivale were relevant. The highest incidence and concentrations of mycotoxins were
      found for deoxynivalenol, followed by zearalenone and beauvericin, both pre
      harvest and at harvest. Other toxins frequently found--for the first time in the
      Netherlands--included T-2 toxin, HT-2 toxin, and moniliformin. The levels of
      deoxynivalenol were positively related to F. graminearum levels, as well as to
      zearalenone levels. Other relationships could not be established. The current
      approach taken in collecting wheat samples and quantifying the presence of
      Fusarium Head Blight species and related mycotoxins is an efficient method to
      obtain insight into the occurrence of these species and toxins in wheat grown
      under natural environmental conditions. It is recommended that this survey be
      repeated for several years to establish inter-annual variability in both species
      composition and mycotoxin occurrence.

PMID- 22624851
TI  - The early gene product EUO is a transcriptional repressor that selectively
      regulates promoters of Chlamydia late genes.
AB  - The obligate intracellular bacterium Chlamydia has an unusual developmental cycle
      in which there is conversion between two forms that are specialized for either
      intracellular replication or propagation of the infection to a new host cell.
      Expression of late chlamydial genes is upregulated during conversion from the
      replicating to the infectious form, but the mechanism for this temporal
      regulation is unknown. We found that EUO, which is expressed from an early gene,
      binds to two sites upstream of the late operon omcAB, but only the downstream
      site was necessary for transcriptional repression. Using gel shift and in vitro
      transcription assays we showed that EUO specifically bound and repressed
      promoters of Chlamydia trachomatis late genes, but not early or mid genes. These
      findings support a role for EUO as a temporal repressor that negatively regulates
      late chlamydial genes and prevents their premature expression. The basis of this
      specificity is the ability of EUO to selectively bind promoter regions of late
      genes, which would prevent their transcription by RNA polymerase. Thus, we
      propose that EUO is a master regulator that prevents the terminal differentiation
      of the replicating form of chlamydiae into the infectious form until sufficient
      rounds of replication have occurred.

PMID- 22624852
TI  - Social environment and HIV risk among MSM in Hanoi and Thai Nguyen.
AB  - Little is known about the effect of the social environment on HIV risk in gay men
      in northern Vietnam, particularly in rural areas. This qualitative research study
      conducted 4 key informant interviews and 30 in-depth interviews of men in two
      northern Vietnamese cities: Hanoi, a large city, and Thai Nguyen, a smaller town.
      Hanoi has experienced a growth in the number of places where gay men can
      socialize, access HIV prevention services, and discuss health issues. Thai Nguyen
      lacks these open venues. However, homosexuality is still highly stigmatized in
      the general population in both cities. This stigma affects the number of partners
      and level of sexual risk of participants. Also, men generally reported little
      communication between partners about sexual risk. While stigma in the general
      community is difficult to change, social environments where gay men can openly
      communicate creates an opportunity for HIV prevention and social support.

PMID- 22624854
TI  - Targeting the human genome-microbiome axis for drug discovery: inspirations from
      global systems biology and traditional Chinese medicine.
AB  - Most chronic diseases impairing current human public health involve not only the
      human genome but also gene-environment interactions, and in the latter case the
      gut microbiome is an important factor. This makes the classical single drug
      receptor target drug discovery paradigm much less applicable. There is widespread
      and increasing international interest in understanding the properties of
      traditional Chinese medicines (TCMs) for their potential utilization as a source
      of new drugs for Western markets as emerging evidence indicates that most TCM
      drugs are actually targeting both the host and its symbiotic microbes. In this
      review, we explore the challenges of and opportunities for harmonizing Eastern
      Western drug discovery paradigms by focusing on emergent functions at the whole
      body level of humans as superorganisms. This could lead to new drug candidate
      compounds for chronic diseases targeting receptors outside the currently accepted
      "druggable genome" and shed light on current high interest issues in Western
      medicine such as drug-drug and drug-diet-gut microbial interactions that will be
      crucial in the development and delivery of future therapeutic regimes optimized
      for the individual patient.

PMID- 22624853
TI  - An affordable, quality-assured community-based system for high-resolution
      entomological surveillance of vector mosquitoes that reflects human malaria
      infection risk patterns.
AB  - BACKGROUND: More sensitive and scalable entomological surveillance tools are
      required to monitor low levels of transmission that are increasingly common
      across the tropics, particularly where vector control has been successful. A
      large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported
      by a community-based (CB) system for trapping adult mosquito densities to monitor
      programme performance. METHODOLOGY: An intensive and extensive CB system for
      routine, longitudinal, programmatic surveillance of malaria vectors and other
      mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es
      Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys
      using either ITT-C or human landing catches (HLC), as well as a cross-sectional
      survey of malaria parasite prevalence in the same housing compounds. RESULTS:
      Community-based ITT-C had much lower sensitivity per person-night of sampling
      than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051,
      0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001
      for Culicines) but only moderately differed from QA surveys with the same trap
      (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An.
      gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night
      of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably
      sensitive in absolute terms (171 versus 169 primary vectors caught) and cost
      effective (153US$ versus 187US$ per An. gambiae caught) because it allowed more
      spatially extensive and temporally intensive sampling (4284 versus 335 trap
      nights distributed over 615 versus 240 locations with a mean number of samples
      per year of 143 versus 141). Despite the very low vectors densities (Annual
      estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the
      only entomological predictor of parasite infection risk (Odds Ratio [95% CI] =
      4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P
      =0.0373). DISCUSSION AND CONCLUSION: CB trapping approaches could be improved
      with more sensitive traps, but already offer a practical, safe and affordable
      system for routine programmatic mosquito surveillance and clusters could be
      distributed across entire countries by adapting the sample submission and quality
      assurance procedures accordingly.

PMID- 22624855
TI  - Retrospective case review of pyriform sinus fistulae of third branchial arch
      origin commonly presenting as acute suppurative thyroiditis in children.
AB  - OBJECTIVE: Abnormalities of the third branchial arch are less common than those
      of the second arch and usually present with left thyroid lobe inflammation. This
      paper describes 15 cases of pyriform sinus fistulae of third branchial arch
      origin usually presenting as recurrent thyroid abscess on the left side. METHOD:
      A retrospective review of 15 cases of third arch fistulae managed 2000 and 2008,
      diagnosed based on histopathology and radiological evidence of a fistulous tract,
      and treated with fistulectomy with left hemithyroidectomy. RESULTS: All patients
      (six boys and nine girls, aged three to 15 years) presented with recurrent low
      neck inflammation. Pre-operative ultrasound, computed tomography fistulography
      and barium swallow demonstrated a third arch fistulous tract, left-sided in all
      cases. The fistula was detected intra-operatively and pathologically in all
      cases. Surgery (successful in all cases) emphasised complete recurrent laryngeal
      nerve and ipsilateral pyriform sinus exposure, to facilitate tract excision, with
      left hemithyroidectomy. There was no recurrence over three to five years' follow
      up. CONCLUSION: Paediatric recurrent low neck inflammatory episodes, due to
      thyroidal abscess, especially left-sided, should raise suspicion of pyriform
      sinus fistulae.

PMID- 22624856
TI  - The effectiveness of video prompting on teaching aquatic play skills for children
      with autism.
AB  - OBJECTIVE: To investigate the effectiveness of the video prompting procedure on
      teaching aquatic play skills and to determine the effects of aquatic exercise
      training on the motor performance of children with autism. DESIGN: A multiple
      probe design across behaviours was used and replicated across subjects for the
      instructional part of this study. Pretest-posttest design was applied for the
      exercise training part of this study. METHODS: Three children with autism were
      taught three aquatic play skills in a one-to-one training format. Aquatic play
      skills intervention and aquatic exercise training were performed separately
      throughout 12 weeks at three sessions per week, each lasting 1 h. The video
      prompting procedure was utilized for the instruction part of this study. RESULTS:
      Video prompting was effective in teaching aquatic play skills to children with
      autism. In addition, aquatic exercise training increased the total motor
      performance scores of all the participants after 12 weeks. According to the
      social validity results, the families gave positive feedback about the learned
      skills and movement capabilities of their children. CONCLUSION: Aquatic play
      skills and swimming pools are favoured for children with autism. This attractive
      intervention is recommended as a means to extend knowledge of leisure skills and
      motor development of children with autism.

PMID- 22624857
TI  - Neural activity associated with self-reflection.
AB  - BACKGROUND: Self-referential cognitions are important for self-monitoring and
      self-regulation. Previous studies have addressed the neural correlates of self
      referential processes in response to or related to external stimuli. We here
      investigated brain activity associated with a short, exclusively mental process
      of self-reflection in the absence of external stimuli or behavioural
      requirements. Healthy subjects reflected either on themselves, a personally known
      or an unknown person during functional magnetic resonance imaging (fMRI). The
      reflection period was initialized by a cue and followed by photographs of the
      respective persons (perception of pictures of oneself or the other person).
      RESULTS: Self-reflection, compared with reflecting on the other persons and to a
      major part also compared with perceiving photographs of one-self, was associated
      with more prominent dorsomedial and lateral prefrontal, insular, anterior and
      posterior cingulate activations. Whereas some of these areas showed activity in
      the "other"-conditions as well, self-selective characteristics were revealed in
      right dorsolateral prefrontal and posterior cingulate cortex for self-reflection;
      in anterior cingulate cortex for self-perception and in the left inferior
      parietal lobe for self-reflection and -perception. CONCLUSIONS: Altogether,
      cingulate, medial and lateral prefrontal, insular and inferior parietal regions
      show relevance for self-related cognitions, with in part self-specificity in
      terms of comparison with the known-, unknown- and perception-conditions. Notably,
      the results are obtained here without behavioural response supporting the
      reliability of this methodological approach of applying a solely mental
      intervention. We suggest considering the reported structures when investigating
      psychopathologically affected self-related processing.

PMID- 22624858
TI  - The role of conserved PEX3 regions in PEX19-binding and peroxisome biogenesis.
AB  - The human peroxins PEX3 and PEX19 are essential for peroxisome biogenesis. They
      mediate the import of membrane proteins as well as the de novo formation of
      peroxisomes. PEX19 binds newly synthesized peroxisomal membrane proteins post
      translationally and directs them to peroxisomes by engaging PEX3, a protein
      anchored in the peroxisomal membrane. After protein insertion into the lipid
      bilayer, PEX19 is released back to the cytosol. Crystallographic analysis
      provided detailed insights into the PEX3-PEX19 interaction and identified three
      highly conserved regions, the PEX19-binding region, a hydrophobic groove and an
      acidic cluster, on the surface of PEX3. Here, we used site-directed mutagenesis
      and biochemical and functional assays to determine the role of these regions in
      PEX19-binding and peroxisome biogenesis. Mutations in the PEX19-binding region
      reduce the affinity for PEX19 and destabilize PEX3. Furthermore, we provide
      evidence for a crucial function of the PEX3-PEX19 complex during de novo
      formation of peroxisomes in peroxisome-deficient cells, pointing to a dual
      function of the PEX3-PEX19 interaction in peroxisome biogenesis. The maturation
      of preperoxisomes appears to require the hydrophobic groove near the base of
      PEX3, presumably by its involvement in peroxisomal membrane protein insertion,
      while the acidic cluster does not appear to be functionally relevant.

PMID- 22624860
TI  - Consequences of occupational food-related hand dermatoses with a focus on protein
      contact dermatitis.
AB  - BACKGROUND: Protein contact dermatitis is a frequent disorder among hand eczema
      patients who have occupational food contact. Knowledge about the consequences of
      having protein contact dermatitis is lacking. OBJECTIVES: To investigate the
      consequences of having occupational skin disease on the hands resulting from food
      handling, with a focus on protein contact dermatitis. MATERIAL AND METHODS: One
      hundred and seventy-eight patients who were identified as having skin disease
      related to occupational food exposure and who answered a questionnaire concerning
      the consequences of their skin disease were included in the study. The patients
      were consecutively examined at Gentofte Hospital, Denmark between 2001 and 2010.
      RESULTS: Seventy-five per cent of patients with protein contact dermatitis had to
      wear gloves at work, and 62.5% reported sick leave lasting for >3 weeks, as
      compared with 60.2% and 30%, respectively, of the patients with other
      occupational food-related hand dermatoses (p = 0.02). Sixty-two per cent and 43%,
      respectively, had to change job because of skin problems (p = 0.02). Atopic
      dermatitis was equally common in the two groups. CONCLUSION: We found that the
      patients with protein contact dermatitis experienced more severe and frequent
      consequences than patients with other food-related hand dermatoses.

PMID- 22624859
TI  - Cannabidiol inhibits angiogenesis by multiple mechanisms.
AB  - BACKGROUND AND PURPOSE: Several studies have demonstrated anti-proliferative and
      pro-apoptotic actions of cannabinoids on various tumours, together with their
      anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD)
      effectively inhibits the growth of different types of tumours in vitro and in
      vivo and down-regulates some pro-angiogenic signals produced by glioma cells. As
      its anti-angiogenic properties have not been thoroughly investigated to date, and
      given its very favourable pharmacological and toxicological profile, here, we
      evaluated the ability of CBD to modulate tumour angiogenesis. EXPERIMENTAL
      APPROACH: Firstly, we evaluated the effect of CBD on human umbilical vein
      endothelial cell (HUVEC) proliferation and viability - through [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and FACS analysis -
      and in vitro motility - both in a classical Boyden chamber test and in a wound
      healing assay. We next investigated CBD effects on different angiogenesis-related
      proteins released by HUVECs, using an angiogenesis array kit and an ELISA
      directed at MMP2. Then we evaluated its effects on in vitro angiogenesis in
      treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into
      collagen gels, and further characterized its effects in vivo using a Matrigel
      sponge model of angiogenesis in C57/BL6 mice. KEY RESULTS: CBD induced HUVEC
      cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion and
      sprouting in vitro, and angiogenesis in vivo in Matrigel sponges. These effects
      were associated with the down-modulation of several angiogenesis-related
      molecules. CONCLUSIONS AND IMPLICATIONS: This study reveals that CBD inhibits
      angiogenesis by multiple mechanisms. Its dual effect on both tumour and
      endothelial cells supports the hypothesis that CBD has potential as an effective
      agent in cancer therapy.

PMID- 22624861
TI  - Late somatic sequelae after treatment of childhood cancer in Slovenia.
AB  - BACKGROUND: This is a long-term follow-up clinical study of adolescents and
      adults, survivors of childhood cancer. We evaluate and analyze the late somatic
      sequelae of childhood cancer treatment. Many such studies are susceptible to a
      strong selection bias, i.e., they employ a limited non-systematic sample of
      patients, based on a clinical hospital that provided the cancer treatment or
      performed the follow-up. To address the issue of selection bias, we perform here
      an analysis of late sequelae on a systematic database of the entire population of
      the children treated for cancer in Slovenia. Due to the specifics of cancer
      treatment procedures in Slovenia, they have all been treated and followed-up in
      the same clinic. METHODS: The data are based on the centralized registry of
      cancer patients in Slovenia and present a controlled and homogeneous collection.
      Late sequelae are evaluated following a modified CTCAE, i.e., the National Cancer
      Institute's Common Terminology Criteria for Adverse Events version 3.0. We use
      survival analysis method to estimate the incidence of and risk for late sequelae,
      where the time variable is measured in years from the diagnosis date, while we
      follow the event of incidence of late sequelae scored other than none. Survival
      analysis is performed using Kaplan Meier estimator and Cox regression model.
      RESULTS: The incidence of mild, moderate, or severe late sequelae of childhood
      cancer treatment significantly decreased from 75% in the group of patients
      diagnosed before 1975 to 55% for those diagnosed after 1995. The Cox regression
      analysis of the risk factors for the incidence of late sequelae identifies three
      significant factors: treatment modalities, age at diagnosis, and primary
      diagnosis. CONCLUSIONS: The change of treatment modalities in terms of
      replacement of surgery and radiotherapy with chemotherapy is the main reason for
      the decrease of the incidence and the risk for late sequelae of childhood cancer
      treatment; treatment modalities including surgery significantly increase the risk
      ratio of late sequelae, while those based on chemotherapy only significantly
      decreases the risk. Risk of late sequelae increases with the diagnosis age:
      younger children are more susceptible to late effects of treatment. Finally,
      primary diagnosis significantly influences the risk for late sequelae, but mostly
      due to the dependency of the treatment modality on the primary diagnosis.

PMID- 22624862
TI  - Prevalence, location and morphology of maxillary sinus septa: systematic review
      and meta-analysis.
AB  - AIM: To gain further insights and resolve conflicting results in the literature
      regarding prevalence, predominant location and morphologic variability of
      maxillary sinus septa. MATERIAL AND METHODS: Electronic and hand searching of
      English literature identified 33 investigations published from 1995 to 2011.
      Septa were defined as at least 2-4 mm in height. RESULTS: Septa were present in
      28.4% of 8923 sinuses investigated (95% confidence interval: 24.3-32.5%).
      Prevalence was significantly higher in atrophic sinuses compared with dentate
      maxillae (p < 0.001). Septa were located in premolar, molar and retromolar
      regions in 24.4%, 54.6% and 21.0% respectively. Orientation of septa was
      transverse in 87.6%, sagittal in 11.1% and horizontal in 1.3% of cases. Septa
      height measured 7.5 mm on average. Complete septa (dividing the sinus into two
      separate cavities) were found in only 0.3%. Other rare conditions included
      multiple septa in one sinus (4.2%) and bilateral septa (17.2%). Septa diagnosis
      using panoramic radiographs yielded incorrect results in 29% of cases.
      CONCLUSIONS: In view of their high overall prevalence and significant morphologic
      variability, 3D radiographic imaging prior to sinus floor augmentation may help
      to reduce complication rates in the presence of maxillary sinus septa.

PMID- 22624865
TI  - Acute and late outcomes of Transcatheter Aortic Valve Implantation (TAVI) for the
      treatment of severe symptomatic aortic stenosis in patients at high- and low
      surgical risk.
AB  - BACKGROUND: This prospective study examines the impact of EuroSCORE and
      transfemoral (TF) or transapical (TA) delivery approach on mortality at 30 days
      and 1 year in patients with severe aortic stenosis implanted with either the
      Edwards SAPIEN Transcatheter Heart Valve (THV) or Medtronic CoreValve. METHODS
      AND RESULTS: TAVI was successfully performed in 293 (97.7%) of 300 patients (TF:
      174, TA: 126, mean EuroSCORE 24.0). The mortality at 30 days and after 1 year was
      6.0% and 17.3%. Mortality depends significantly on the logistic EuroSCORE with a
      30-day odds ratio (OR) of 1.92 (95% CI 1.41 to 2.62, P < 0.001) and after 1 year
      of 1.67 (95% CI 1.34 to 2.08, P < 0.001). Mortality in patients with a logistic
      EuroSCORE <15 (n = 113) or >=15 (n = 187) at 30 days was 0.9% versus 9.1% and
      after 1 year 7.1% versus 23.5% demonstrating significantly less mortality (P <
      0.001) in patients with lower logistic EuroSCOREs. In this specific setup of our
      center there was no significant difference (P = 0.553) in mortality regarding the
      technical approach for TA (4.0% and 15.9%) and for TF (7.5% and 18.4%). Severe
      cardiac complications occurred in 20 patients (6.7%) with a 30-day mortality of
      45.0%. CONCLUSION: The mortality in patients undergoing TAVI correlates
      significantly with the logistic EuroSCORE. Patients with a logistic EuroSCORE <15
      can be implanted, with a low 30-day mortality and good long-term outcome over 1
      year.

PMID- 22624867
TI  - Sulfoform generation from an orthogonally protected disaccharide.
AB  - An orthogonally protected disaccharide (GlcN(alpha1->4)Glc) with a beta-linked 2'
      aminoethyl linker was used to generate a series of sulfated derivatives
      (sulfoforms), with a 6-O-sulfate on the glucose residue and one or more sulfate
      esters on the terminal glucosamine. Deprotection and sulfonation steps were
      performed in solution and in variable order, with isolated yields of 36-54% (85
      90% per operation) after HPLC purification. The modular deprotection-sulfonation
      sequences can be performed with efficient recovery of the polysulfate products,
      and avoids complications associated with heterogeneous reactivity in solid-phase
      synthesis.

PMID- 22624868
TI  - Asset ownership among households caring for orphans and vulnerable children in
      rural Zimbabwe: the influence of ownership on children's health and social
      vulnerabilities.
AB  - The high prevalence of human immunodeficiency virus/acquired immune deficiency
      syndrome in sub-Saharan Africa has resulted in a dramatic increase in orphans and
      vulnerable children (OVC) over the past decade. These children typically rely on
      extended family networks for support, but the magnitude of the crisis has
      resulted in traditional familial networks becoming overwhelmed and more
      economically and socially vulnerable. Previous research consistently demonstrates
      the positive influence of household asset ownership on children's well-being.
      Using data from impoverished households caring for OVC in rural Manicaland
      Province, Zimbabwe, this study explores the influence of household asset
      ownership on OVC health vulnerability (HV) and social vulnerability (SV).
      Findings indicate that asset ownership is associated with significantly lower SV,
      in terms of school attendance and birth registration. Yet, assets do not emerge
      as a direct influence of OVC HV as measured by disease and chronic illness,
      although having a chronically ill adult in the household increases HV. These
      findings suggest that asset ownership, specifically a combination of fixed and
      movable assets, may offset the influence of other risk factors for children's SV.

PMID- 22624869
TI  - The propensity for consuming ethanol in Drosophila requires rutabaga adenylyl
      cyclase expression within mushroom body neurons.
AB  - Alcohol activates reward systems through an unknown mechanism, in some cases
      leading to alcohol abuse and dependence. Herein, we utilized a two-choice
      Capillary Feeder assay to address the neural and molecular basis for ethanol self
      administration in Drosophila melanogaster. Wild-type Drosophila shows a
      significant preference for food containing between 5% and 15% ethanol. Preferred
      ethanol self-administration does not appear to be due to caloric advantage, nor
      due to perceptual biases, suggesting a hedonic bias for ethanol exists in
      Drosophila. Interestingly, rutabaga adenylyl cyclase expression within intrinsic
      mushroom body neurons is necessary for robust ethanol self-administration. The
      expression of rutabaga in mushroom bodies is also required for both appetitive
      and aversive olfactory associative memories, suggesting that reinforced behavior
      has an important role in the ethanol self-administration in Drosophila. However,
      rutabaga expression is required more broadly within the mushroom bodies for the
      preference for ethanol-containing food than for olfactory memories reinforced by
      sugar reward. Together these data implicate cAMP signaling and behavioral
      reinforcement for preferred ethanol self-administration in D. melanogaster.

PMID- 22624870
TI  - Effects of a structured educational programme on patient-controlled analgesia
      (PCA) for gynaecological patients in South Korea.
AB  - AIMS AND OBJECTIVES: The purpose of the study was to evaluate the effects of a
      structured educational programme on the patient-controlled analgesia device in
      terms of postoperative pain, dose of analgesics used, adverse reactions, patient
      knowledge and attitudes of patient-controlled analgesia and patient satisfaction
      with postoperative pain management among gynaecological patients in South Korea.
      BACKGROUND: Patient-controlled intravenous analgesia has become the most common
      method to manage postoperative pain. Although the patient-controlled analgesia
      device can be very effective in managing pain, patients using external pump
      delivery have several problems because of their lack of knowledge of patient
      controlled analgesia. To minimise these problems, nursing interventions that may
      decrease the number of problems should be developed and adopted into clinical
      practice. DESIGN: A non-equivalent control group, non-synchronised design.
      METHODS: The participants were 79 patients who had gynaecological surgery under
      general anaesthesia. Of the 79 patients, 39 were assigned to the experimental
      group and 40 to the control group. A day before surgery, 40 minutes of structured
      education on the patient-controlled analgesia device was provided individually to
      the patients in the experimental group using both a CD-ROM and brochure. RESULTS:
      Pain level and adverse reactions were significantly lower in the experimental
      group than in the control group. Furthermore, the analgesic dose administered and
      the level of patient satisfaction with postoperative pain management increased
      significantly in the experimental group compared with the control group.
      CONCLUSION: A structured educational programme on the patient-controlled
      analgesia can be an effective nursing intervention for pain management in
      gynaecological patients. RELEVANCE TO CLINICAL PRACTICE: Nurses caring for the
      patients who are using the patient-controlled analgesia should provide a
      structured educational programme to increase knowledge of pain management with
      patient-controlled analgesia, patient satisfaction with pain management, as well
      as more effective management of the pain and adverse reaction caused by patient
      controlled analgesia.

PMID- 22624871
TI  - Incidence of postpartum anal incontinence among Indians and black Africans in a
      resource-constrained country.
AB  - OBJECTIVE: To estimate the prevalence of postpartum anal incontinence (AI) in a
      low-resource setting and to highlight any interracial variation in the incidence.
      METHODS: A prospective observational cohort study was conducted amongst the
      Indian and black African populations of KwaZulu-Natal, South Africa. A group of
      1331 women who delivered at term completed a questionnaire on the symptoms of AI
      in both the prenatal and postpartum periods. The prevalence, incidence and
      persistence of AI were compared by race, age, parity, and mode of delivery.
      RESULTS: The prenatal prevalence of incontinence of flatus was 26.3%, with a 6
      week postpartum incidence of 61.1% and a 6-month persistence of 6.4%. Interracial
      variation in the incidence of AI was evident. Prenatal incontinence of flatus was
      more frequent among Indians than black Africans (34.1% versus 24.5%; P=0.002). By
      contrast, the 6-week postpartum incidence of incontinence of flatus was higher
      among black Africans than Indians (63.2% versus 53.1%; P=0.018). The incidence of
      AI was significantly lower among women who underwent cesarean delivery; parity
      and age did not show significant associations. CONCLUSION: Postpartum AI in a low
      resource setting is problematic, with interracial variation in incidence. The
      mode of delivery possibly influences subsequent development of AI.

PMID- 22624872
TI  - Suppression of erythroid development in vitro by Plasmodium vivax.
AB  - BACKGROUND: Severe anaemia due to dyserythropoiesis has been documented in
      patients infected with Plasmodium vivax, however the mechanism responsible for
      anaemia in vivax malaria is poorly understood. In order to better understand the
      role of P. vivax infection in anaemia the inhibition of erythropoiesis using
      haematopoietic stem cells was investigated. METHODS: Haematopoietic stem
      cells/CD34+ cells, isolated from normal human cord blood were used to generate
      growing erythroid cells. Exposure of CD34+ cells and growing erythroid cells to
      P. vivax parasites either from intact or lysed infected erythrocytes (IE) was
      examined for the effect on inhibition of cell development compared with untreated
      controls. RESULTS: Both lysed and intact infected erythrocytes significantly
      inhibited erythroid growth. The reduction of erythroid growth did not differ
      significantly between exposure to intact and lysed IE and the mean growth
      relative to unexposed controls was 59.4 +/- 5.2 for lysed IE and 57 +/- 8.5% for
      intact IE. Interestingly, CD34+ cells/erythroid progenitor cells were susceptible
      to the inhibitory effect of P. vivax on cell expansion. Exposure to P. vivax also
      inhibited erythroid development, as determined by the reduced expression of
      glycophorin A (28.1%) and CD 71 (43.9%). Moreover, vivax parasites perturbed the
      division of erythroid cells, as measured by the Cytokinesis Block Proliferation
      Index, which was reduced to 1.35 +/- 0.05 (P-value<0.01) from a value of 2.08 +/-
      0.07 in controls. Neither TNF-a nor IFN-g was detected in the culture medium of
      erythroid cells treated with P. vivax, indicating that impaired erythropoiesis
      was independent of these cytokines. CONCLUSIONS: This study shows for the first
      time that P. vivax parasites inhibit erythroid development leading to ineffective
      erythropoiesis and highlights the potential of P. vivax to cause severe anaemia.

PMID- 22624873
TI  - Bone volume and regional density of the central tarsal bone detected using
      computed tomography in a cross-sectional study of adult racing greyhounds.
AB  - AIMS: To determine whether left-to-right asymmetry of the central tarsal bone
      (CTB) of racing greyhounds was detectable using computed tomography (CT) in live
      dogs; to quantify the asymmetry in terms of average bone volume, volumetric bone
      mineral density (vBMD), and dorsal cortical shape, and to determine if age,
      gender, bodyweight, number of starts or history of tarsal injury were significant
      covariates. METHODS: One trainer supplied 11 male and seven female, unrelated,
      skeletally mature, actively racing greyhounds, including dogs with a history of
      tarsal injury diagnosed by the trainer and/or track veterinarian (n=8), and dogs
      without a history of tarsal injury (n=10). Using CT, standardised parameters of
      the CTB were measured including volume and average vBMD of the left and right
      CTB, vBMD of regions within the CTB, and bone shape. RESULTS: There was no
      difference in the volumes of the left and right CTB and no association with
      number of racing starts. Volume of CTB in dogs with a history of tarsal injury
      was greater than in dogs with no history of injury (p<0.001). Mean vBMD of the
      right was greater than the left CTB (p=0.004), and was independent of history of
      injury, gender, bodyweight, and number of starts. Males with a history of injury
      weighed more than those with no history of injury (p=0.004). The region of
      greatest difference in vBMD between right and left limbs was the
      centrodorsomedial aspect of the CTB. Middle plantar ligament enthesiopathies and
      fractures of tarsal bones other than the central tarsal bone were identified in
      dogs with and without a history of tarsal injury. CONCLUSIONS: Significant left
      to-right asymmetry of the CTB in racing greyhounds was detected using CT.
      Contrary to previous suggestions, the asymmetry was not associated with the
      number of racing starts. We propose that the majority of the adaptive modelling
      of the CTB occurred rapidly following the onset of counter-clockwise training,
      with little further modelling throughout the racing career of the dog, however
      further investigation is warranted. CLINICAL RELEVANCE: This study described a
      technique using CT for imaging the CTB in live dogs, which opens the way for a
      longitudinal study of bone modelling of the CTB in response to training and
      racing in a counter-clockwise direction.

PMID- 22624874
TI  - Selection strategy to generate aptamer pairs that bind to distinct sites on
      protein targets.
AB  - Many analytical techniques benefit greatly from the use of affinity reagent
      pairs, wherein each reagent recognizes a discrete binding site on a target. For
      example, antibody pairs have been widely used to dramatically increase the
      specificity of enzyme linked immunosorbent assays (ELISA). Nucleic acid-based
      aptamers offer many advantageous features relative to protein-based affinity
      reagents, including well-established chemical synthesis, thermostability, and low
      production cost. However, the generation of suitable aptamer pairs has posed a
      significant challenge, and few such pairs have been reported to date. To address
      this important challenge, we present multivalent aptamer isolation systematic
      evolution of ligands by exponential enrichment (MAI-SELEX), a technique designed
      for the efficient selection of aptamer pairs. In contrast to conventional
      selection methods, our method utilizes two selection modules to generate separate
      aptamer pools that recognize distinct binding sites on a single target. Using MAI
      SELEX, we have isolated two groups of 2'-fluoro-modified RNA aptamers that
      specifically recognize the alphaV or beta3 subunits of integrin alphaVbeta3.
      These aptamers exhibit low nanomolar affinities for their targets, with minimal
      cross-reactivity to other closely related integrin homologues. Moreover, we show
      that these aptamer pairs do not interfere with each other's binding and
      effectively detect the target even in complex mixtures such as undiluted serum.

PMID- 22624875
TI  - Superresolution imaging of ribosomes and RNA polymerase in live Escherichia coli
      cells.
AB  - Quantitative spatial distributions of ribosomes (S2-YFP) and RNA polymerase
      (RNAP; beta'-yGFP) in live Escherichia coli are measured by superresolution
      fluorescence microscopy. In moderate growth conditions, nucleoid-ribosome
      segregation is strong, and RNAP localizes to the nucleoid lobes. The mean copy
      numbers per cell are 4600 RNAPs and 55,000 ribosomes. Only 10-15% of the
      ribosomes lie within the densest part of the nucleoid lobes, and at most 4% of
      the RNAPs lie in the two ribosome-rich endcaps. The predominant observed
      diffusion coefficient of ribosomes is D(ribo) = 0.04 um(2) s(-1), attributed to
      free mRNA being translated by one or more 70S ribosomes. We find no clear
      evidence of subdiffusion, as would arise from tethering of ribosomes to the DNA.
      The degree of DNA-ribosome segregation strongly suggests that in E. coli most
      translation occurs on free mRNA transcripts that have diffused into the ribosome
      rich regions. Both RNAP and ribosome radial distributions extend to the
      cytoplasmic membrane, consistent with the transertion hypothesis. However, few if
      any RNAP copies lie near the membrane of the endcaps. This suggests that if
      transertion occurs, it exerts a direct radially expanding force on the nucleoid,
      but not a direct axially expanding force.

PMID- 22624876
TI  - Development of a deletion and genetic linkage map for the 5A and 5B chromosomes
      of wheat (Triticum aestivum).
AB  - The aims of the present study were to provide deletion maps for wheat ( Triticum
      aestivum  L.) chromosomes 5A and 5B and a detailed genetic map of chromosome 5A
      enriched with popular microsatellite markers, which could be compared with other
      existing maps and useful for mapping major genes and quantitative traits loci
      (QTL). Physical mapping of 165 gSSR and EST-SSR markers was conducted by
      amplifying each primer pair on Chinese Spring, aneuploid lines, and deletion
      lines for the homoeologous group 5 chromosomes. A recombinant inbred line (RIL)
      mapping population that is recombinant for only chromosome 5A was obtained by
      crossing the wheat cultivar Chinese Spring and the disomic substitution line
      Chinese Spring-5A dicoccoides and was used to develop a genetic linkage map of
      chromosome  5A. A total of 67 markers were found polymorphic between the parental
      lines and were mapped in the RIL population. Sixty-three loci and the Q gene were
      clustered in three linkage groups ordered at a minimum LOD score of 5, while four
      loci remained unlinked. The whole genetic 5A chromosome map covered 420.2 cM,
      distributed among three linkage groups of 189.3, 35.4, and 195.5 cM. The EST
      sequences located on chromosomes 5A and 5B were used for comparative analysis
      against  Brachypodium distachyon  (L.) P. Beauv. and rice ( Oryza sativa  L.)
      genomes to resolve orthologous relationships among the genomes of wheat and the
      two model species.

PMID- 22624878
TI  - The role of CD98hc in mouse macrophage functions.
AB  - CD98hc is a type II transmembrane protein that covalently links to one of several
      L-type amino acid transporters. CD98hc was first identified as a lymphocyte
      activation marker. In this study, we examined the role that CD98hc plays in the
      functions of macrophages using tissue specific knock-out miceCD98hc (CD98hc(flox/
      )LysM-cre mice). When isolated peritoneal macrophages were incubated for 48 h,
      the macrophages obtained from the knock-out mice showed round-shaped
      morphologies, while almost all of the cells obtained from the control mice were
      spindle-shaped. The macrophage functions such as the antigen-presenting,
      phagocytic, and fusion activities, have been reported to decrease in CD98hc
      deficient peritoneal macrophages. In addition, when the CD98hc deficient
      macrophages were stimulated with either IFN-gamma/LPS or IL-4, the production of
      NO(2) or arginase-I decreased in comparison to that observed in the control
      macrophages. These findings show that the CD98hc molecules play an important role
      in the activation and functions of macrophages.

PMID- 22624877
TI  - Recruitment and dynamics of proteasome association with rhTRIM5alpha cytoplasmic
      complexes during HIV-1 infection.
AB  - A variety of proteins have been identified that restrict infection by different
      viruses. One such restriction factor is the rhesus macaque variant of TRIM5alpha
      (rhTRIM5alpha), which potently blocks infection by HIV-1. The block to infection
      mediated by rhTRIM5alpha occurs early after entry into the host cell, generally
      prior to reverse transcription. However, proteasome inhibitors reveal an
      intermediate step of restriction in which virus can complete reverse
      transcription, but still fails to infect the cell. While proteasome inhibitors
      have been a useful tool in understanding how restriction takes place, the role of
      the proteasome itself during restriction has not yet been examined. Here, we
      characterize the interaction of rhTRIM5alpha and incoming virions with the
      proteasome. We show that proteasomes localize to rhTRIM5alpha cytoplasmic bodies,
      and this localization is more evident when the activity of the proteasome is
      inhibited pharmacologically. We also show that restricted virus associates with
      complexes of proteasomes and rhTRIM5alpha, suggesting that rhTRIM5alpha utilizes
      the proteasome during restriction. Finally, live cell imaging experiments reveal
      that virus associates with proteasomes, and proteasome inhibition affects the
      duration of association. Taken together, these studies implicate the proteasome
      as playing a functional role during rhTRIM5alpha restriction of incoming virions.

PMID- 22624879
TI  - Mother and child behaviour in very preterm and term dyads at 6 and 8 years.
AB  - AIM: Mothers of very preterm children have been reported to behave less
      sensitively and to be more controlling. It is unknown whether this is the result
      of maternal factors or due to maternal adaptation to children's cognitive
      problems. METHOD: We investigated a geographically defined prospective whole
      population sample of very low birthweight (<1500 g) or very preterm (<32 wks'
      gestation; VLBW/VP) children (n = 267, 124 females, 143 males) and a comparison
      group born at term (n = 298, 146 females, 152 males) in Germany. Mother-child
      interactions were videotaped during a play situation and analysed with a
      standardized coding system at children's mean ages of 6 years 3 months and 8
      years 5 months. RESULTS: At both 6 years 3 months and 8 years 5 months, VLBW/VP
      children were less task persistent and socially active (p<0.001) whereas their
      mothers behaved less sensitively and were more controlling than term mother-child
      dyads (p<0.001). Cross-sectional group differences in maternal behaviour remained
      when scores where adjusted for social factors but disappeared once adjusted for
      child IQ. High maternal sensitivity predicted higher task persistence (p<0.001),
      in particular in those children with cognitive problems. INTERPRETATION: Mothers
      of VLBW/VP children adapt their behaviour to their children's level of cognitive
      functioning. High maternal sensitivity is particularly beneficial for task
      persistence in children with cognitive deficits.

PMID- 22624880
TI  - Tacrine-silibinin codrug shows neuro- and hepatoprotective effects in vitro and
      pro-cognitive and hepatoprotective effects in vivo.
AB  - A codrug of the anti-Alzheimer drug tacrine and the natural product silibinin was
      synthesized. The codrug's biological and pharmacological properties were compared
      to an equimolar mixture of the components. The compound showed potent acetyl- and
      butyrylcholinesterase inhibition. In a cellular hepatotoxicity model, analyzing
      the influence on viability and mitochondria of hepatic stellate cells (HSC), the
      toxicity of the codrug was markedly reduced in comparison to that of tacrine.
      Using a neuronal cell line (HT-22), a neuroprotective effect against glutamate
      induced toxicity could be observed that was absent for the 1:1 mixture of
      components. In subsequent in vivo experiments in rats, in contrast to the effects
      seen after tacrine treatment, after administration of the codrug no
      hepatotoxicity and no induction of the cytochrome P450 system were noticed. In a
      scopolamine-induced cognitive impairment model using Wistar rats, the codrug was
      as potent as tacrine in reversing memory dysfunction. The tacrine-silibinin
      codrug shows high AChE and BChE inhibition, neuroprotective effects, lacks
      tacrine's hepatotoxicity in vitro and in vivo, and shows the same pro-cognitive
      effects in vivo as tacrine, being superior to the physical mixture of tacrine and
      silibinin in all these regards.

PMID- 22624881
TI  - Plant PRMTs broaden the scope of arginine methylation.
AB  - Post-translational methylation at arginine residues is one of the most important
      covalent modifications of proteins, involved in a myriad of essential cellular
      processes in eukaryotes, such as transcriptional regulation, RNA processing,
      signal transduction, and DNA repair. Methylation at arginine residues is
      catalyzed by a family of enzymes called protein arginine methyltransferases
      (PRMTs). PRMTs have been extensively studied in various taxa and there is a
      growing tendency to unveil their functional importance in plants. Recent studies
      in plants revealed that this evolutionarily conserved family of enzymes regulates
      essential traits including vegetative growth, flowering time, circadian cycle,
      and response to high medium salinity and ABA. In this review, we highlight recent
      advances in the field of post-translational arginine methylation with special
      emphasis on the roles and future prospects of this modification in plants.

PMID- 22624882
TI  - Efficient and specific modifications of the Drosophila genome by means of an easy
      TALEN strategy.
AB  - Technology development has always been one of the forces driving breakthroughs in
      biomedical research. Since the time of Thomas Morgan, Drosophilists have, step by
      step, developed powerful genetic tools for manipulating and functionally
      dissecting the Drosophila genome, but room for improving these technologies and
      developing new techniques is still large, especially today as biologists start to
      study systematically the functional genomics of different model organisms,
      including humans, in a high-throughput manner. Here, we report, for the first
      time in Drosophila, a rapid, easy, and highly specific method for modifying the
      Drosophila genome at a very high efficiency by means of an improved transcription
      activator-like effector nuclease (TALEN) strategy. We took advantage of the very
      recently developed "unit assembly" strategy to assemble two pairs of specific
      TALENs designed to modify the yellow gene (on the sex chromosome) and a novel
      autosomal gene. The mRNAs of TALENs were subsequently injected into Drosophila
      embryos. From 31.2% of the injected F(0) fertile flies, we detected inheritable
      modification involving the yellow gene. The entire process from construction of
      specific TALENs to detection of inheritable modifications can be accomplished
      within one month. The potential applications of this TALEN-mediated genome
      modification method in Drosophila are discussed.

PMID- 22624883
TI  - A profile of native integration sites used by phiC31 integrase in the bovine
      genome.
AB  - The Streptomyces phage phiC31 integrase can efficiently target attB-bearing
      transgenes to endogenous pseudo attP sites within mammalian genomes. To better
      understand the activity of phiC31 integrase in the bovine genome, DNA sequences
      of 44 integration events were analyzed, and 32 pseudo attP sites were identified.
      The majority of these sites share a sequence motif that contains inverted repeats
      and has similarities to wild-type attP site. Genomic DNA flanking these sites
      typically contained repetitive sequence elements, such as short and long
      interspersed repetitive elements. These sequence features indicate that DNA
      sequence recognition plays an important role in guiding phiC31-mediated site
      specific integration. In addition, BF27 integration hotspot sites were identified
      in the bovine genome, which accounted for 13.6% of all isolated integration
      events and mapped to an intron of the deleted in liver cancer 1 (DLC1) gene. Also
      we found that the pseudo attP sites in the bovine genome had other features in
      common with those in the human genome. This study represents the first time that
      the sequence features of pseudo attP sites in the bovine genome were analyzed. We
      conclude that this site-specific integrase system has great potential for applied
      modifications of the bovine genome.

PMID- 22624884
TI  - A high-throughput method for screening Arabidopsis mutants with disordered
      abiotic stress-induced calcium signal.
AB  - It is established that different stresses cause signal-specific changes in
      cellular Ca(2+) level, which function as messengers in modulating diverse
      physiological processes. These calcium signals are important for stress
      adaptation. Though numbers of downstream components of calcium signal cascades
      have been identified, upstream events in calcium signal remain elusive,
      specifically components required for calcium signal generation due to the lack of
      high-throughput genetic assay. Here, we report the development of an easy and
      efficient method in a forward genetic screen for Ca(2+) signals-deficient mutants
      in Arabidopsis thaliana. Using this method, 121 mutants with disordered NaCl- and
      H(2)O(2)-induced Ca(2+) signals are isolated.

PMID- 22624885
TI  - Hand eczema: prevalence and risk factors of hand eczema in a population of 2274
      healthcare workers.
AB  - BACKGROUND: Healthcare workers are at increased risk of developing hand eczema.
      OBJECTIVES: To investigate the prevalence and severity of self-reported hand
      eczema, and to relate the findings to demographic data, occupation, medical
      speciality, wards, shifts, and working hours. PATIENTS/MATERIALS/METHODS: A
      survey of 3181 healthcare workers was performed. Data were analysed with logistic
      regression. Data on sick leave and notification to the authorities were obtained.
      RESULTS: The response rate was 71% (2274 of 3181). The 1-year prevalence of hand
      eczema was 21%, and was positively associated with atopic dermatitis, younger
      age, male sex (male doctors), and working hours. Eighty nine per cent of subjects
      reported mild/moderate lesions. Atopic dermatitis was the only factor
      significantly related to severity. Sick leave was reported by 8% of subjects, and
      notification to the authorities by 12%. CONCLUSIONS: The 21% prevalence of hand
      eczema in healthcare workers is double the prevalence in the background
      population. Eleven per cent of hand eczema patients reported severe/very severe
      eczema. No significant differences were found between professions or medical
      specialities with respect to prevalence or severity, but cultural differences
      between professions with respect to coping with the eczema were significant.
      Atopic dermatitis was related to increased prevalence and severity, and
      preventive efforts should be made for healthcare workers with atopic dermatitis.

PMID- 22624886
TI  - Prevalence and factors associated with irritable bowel syndrome among medical
      students of Karachi, Pakistan: a cross-sectional study.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) and its association with stress, has
      not been studied among university students in Pakistan. We investigated the
      prevalence and the pattern of anxiety related IBS symptoms among medical students
      of Karachi. FINDINGS: An observational case-control study was carried out at
      three medical colleges of Karachi, Pakistan. Random sampling was done on 360
      medical students. Data was collected using validated tools "Rome III Criteria"
      and "Generalized Anxiety Disorder Questionnaire". Participants with IBS were
      diagnosed on the criteria having experienced abdominal discomfort at least 2-3
      days/month associated with high level of anxiety. The apparent prevalence of IBS
      was found to be 28.3%, with a predominance of 87 (85.29%) females (85.29%) over
      males (14.71%). The psychological symptoms of anxiety were encountered in 57
      (55.8%) participants with IBS, among which males were 15.7% and females 84.2%
      respectively. CONCLUSION: Students who more frequently suffer with mental stress
      and anxiety are more associated with IBS.

PMID- 22624888
TI  - Keratoconus.

PMID- 22624889
TI  - Reversed needle pass clear-corneal or limbal incision suturing technique using
      the 3-throw (1-1-1) adjustable square knot.
AB  - A single radial suture is required for a corneal or limbal incision that does not
      seal despite stromal hydration. In the traditional technique for placing this
      suture, the needle enters from the corneal side of the limbal incision and exits
      toward the scleral side and the suture is usually tied with a 3-1-1 surgical
      knot. We present an improved suturing technique in which the needle path is
      reversed. The needle enters on the scleral side of the limbal incision, exits on
      the corneal side toward the apex, and is tied with an adjustable 1-1-1 knot.

PMID- 22624887
TI  - Test-retest reliability of multidimensional dyspnea profile recall ratings in the
      emergency department: a prospective, longitudinal study.
AB  - BACKGROUND: Dyspnea is among the most common reasons for emergency department
      (ED) visits by patients with cardiopulmonary disease who are commonly asked to
      recall the symptoms that prompted them to come to the ED. The reliability of
      recalled dyspnea has not been systematically investigated in ED patients.
      METHODS: Patients with chronic or acute cardiopulmonary conditions who came to
      the ED with dyspnea (N = 154) completed the Multidimensional Dyspnea Profile
      (MDP) several times during the visit and in a follow-up visit 4 to 6 weeks later
      (n = 68). The MDP has 12 items with numerical ratings of intensity,
      unpleasantness, sensory qualities, and emotions associated with how breathing
      felt when participants decided to come to the ED (recall MDP) or at the time of
      administration ("now" MDP). The recall MDP was administered twice in the ED and
      once during the follow-up visit. Principal components analysis (PCA) with varimax
      rotation was used to assess domain structure of the recall MDP. Internal
      consistency reliability was assessed with Cronbach's alpha. Test-retest
      reliability was assessed with intraclass correlation coefficients (ICCs) for
      absolute agreement for individual items and domains. RESULTS: PCA of the recall
      MDP was consistent with two domains (Immediate Perception, 7 items, Cronbach's
      alpha = .89 to .94; Emotional Response, 5 items; Cronbach's alpha = .81 to .85).
      Test-retest ICCs for the recall MDP during the ED visit ranged from .70 to .87
      for individual items and were .93 and .94 for the Immediate Perception and
      Emotional Response domains. ICCs were much lower for the interval between the ED
      visit and follow-up, both for individual items (.28 to .66) and for the Immediate
      Perception and Emotional Response domains (.72 and .78, respectively).
      CONCLUSIONS: During an ED visit, recall MDP ratings of dyspnea at the time
      participants decided to seek care in the ED are reliable and sufficiently stable,
      both for individual items and the two domains, that a time lag between arrival
      and questionnaire administration does not critically affect recall of perceptual
      and emotional characteristics immediately prior to the visit. However, test
      retest reliability of recall over a 4- to 6-week interval is poor for individual
      items and significantly attenuated for the two domains.

PMID- 22624890
TI  - Comparison of stromal hydration techniques for clear corneal cataract incisions:
      conventional hydration versus anterior stromal pocket hydration.
AB  - Anterior stromal pocket hydration was compared with conventional hydration for
      preventing wound leak after 2.8 mm uniplanar clear corneal incisions (CCIs) in
      patients having routine cataract surgery. Conventional hydration involves
      hydration of the lateral walls of the main incision with visible whitening of the
      stroma. The anterior stromal pocket hydration technique involves creation of an
      additional supraincisional stromal pocket overlying the main incision, which is
      then hydrated instead of the main incision. Sixty-six eyes of 48 patients were
      included in the data analysis with 33 assigned to each study group. The anterior
      stromal pocket hydration technique was significantly better than conventional
      hydration in preventing wound leak due to direct pressure on the posterior lip of
      the incision.

PMID- 22624891
TI  - Treatment of late-onset capsular distension syndrome with a neodymium:YAG laser
      peripheral iridotomy and anterior capsulotomy.
AB  - We describe a new approach to treat late-onset capsular distension syndrome in
      which the fluid in the capsular bag is cloudy and prevents a posterior
      neodymium:YAG (Nd:YAG) laser capsulotomy. A peripheral laser iridotomy is created
      through which the anterior lens capsule peripheral to the IOL optic is accessed.
      This opening in the iris provides an access point through which an anterior
      Nd:YAG laser capsulotomy can be performed. Following disruption of the anterior
      lens capsule, the capsular fluid is released into the anterior chamber and
      absorbed through the inherent drainage system of the eye. This approach avoids
      the need for a more invasive surgical intervention.

PMID- 22624892
TI  - Macular morphology assessed by optical coherence tomography image segmentation
      after femtosecond laser-assisted and standard cataract surgery.
AB  - PURPOSE: To evaluate and compare thickness changes in the retinal layers in the
      macula with optical coherence tomography (OCT) segmentation software after
      femtosecond laser-assisted phacoemulsification (study group) and conventional
      phacoemulsification (control group). SETTING: Department of Ophthalmology,
      Semmelweis University, Budapest, Hungary. DESIGN: Case-control study. METHODS:
      Total retinal thickness of the macula was evaluated using Stratus OCT 4 to 8
      weeks postoperatively. The OCT images were segmented using OCT retinal image
      analysis software. Regional thickness data in the central area, inner rings, and
      outer rings were obtained and absolute and relative thicknesses of the individual
      retinal layers in the 2 study groups compared. Relative thickness was calculated
      as the ratio of the retinal layer to the total retinal thickness. RESULTS: All
      surgeries were uneventful. Statistically significant differences were found in
      absolute outer nuclear layer thickness and relative outer nuclear layer thickness
      in the inner and outer macular rings between the 2 groups. After adjusting for
      effective phaco time in multivariate modeling, type of surgery showed a
      significantly lower relative outer nuclear layer ratio in the inner retinal ring
      (0.26 with 95% confidence interval [CI], 0.25-0.27 versus 0.28 with 95% CI, 0.27
      0.29; P=.03) and in the outer retinal ring (0.27 with 95% CI, 0.25-0.28 versus
      0.29 with 95% CI, 0.28-0.31; P=.02) in the study group. CONCLUSION: After
      cataract surgery, macular edema was detectable mainly in the outer nuclear layer
      in both groups but was significantly less using the femtosecond laser platform.

PMID- 22624893
TI  - Visual simulation through different intraocular lenses using adaptive optics:
      effect of tilt and decentration.
AB  - PURPOSE: To analyze visual quality differences between intraocular lenses (IOLs)
      and assess the impact of IOL decentration and tilt on visual quality. SETTING:
      University of Valencia, Valencia, Spain. DESIGN: Cohort study. METHODS: The crx1
      adaptive optics visual simulator was used to simulate the wavefront aberration
      pattern of 2 commercially available aspheric aberration-correcting IOLs (Acrysof
      IQ SN60WF and Tecnis ZA9003) and 2 spherical IOLs (Akreos Adapt and Triplato) in
      5 situations: centered, decentered 0.2 mm and 0.4 mm, and tilted 2 degrees and 4
      degrees. Monocular distance visual acuity at 100%, 50%, and 10% contrast and the
      depth of focus were measured. RESULTS: Ten eyes of 10 patients were evaluated.
      When the IOLs were centered, there were no differences in visual acuity between
      the 4 IOLs at any contrast. The aberration-correcting IOLs were more sensitive to
      tilt and decentration than the spherical IOLs; Tecnis ZA9003 IOL was the most
      sensitive to decentration and the Acrysof IQ SN60WF IOL was the most sensitive to
      tilt. Higher residual spherical aberration slightly improved depth of focus and
      the tolerance to defocus. CONCLUSIONS: The results in this study suggest that the
      aspheric aberration-correcting and spherical IOLs provided comparable visual
      quality when centered in eyes in which the corneal higher-order aberrations are
      those of the average of the human cornea. Tilt and decentration of the IOLs had
      an impact on visual quality, with aberration-correcting IOLs having a greater
      effect than the spherical IOLs.

PMID- 22624894
TI  - Ocular Trauma Score as a predictor of final visual outcomes in traumatic cataract
      cases in pediatric patients.
AB  - PURPOSE: To validate the predictive value of the Ocular Trauma Score (OTS) in
      children with traumatic cataract. DESIGN: Retrospective cohort study. SETTING:
      Tertiary eye care center at nexus of Gujarat, Madhya Pradesh, and Rajasthan
      states, central Western India. METHODS: After meeting inclusion criteria, eyes
      with traumatic cataract were enrolled and examined to review comorbidities caused
      by trauma. Surgery was performed for traumatic cataract, intraocular lenses were
      implanted, and patients were treated for amblyopia, as applicable. Patients were
      reexamined 6 weeks postoperatively. Based on ocular trauma described according to
      the Birmingham Eye Trauma Terminology System, the patients were divided into 2
      traumatic cataract groups: open-globe injury and closed-globe injury. The
      relationship between final corrected distance visual acuity (CDVA) and
      demographic and clinical variables was analyzed. Visual outcomes were predicted
      using the OTS, and the predictions were compared with actual outcomes using
      statistical tests. RESULTS: The study enrolled 354 children. Six weeks
      postoperatively, the CDVA was better than 20/200 in 181 eyes (63.0%) and 20/40 or
      better in 110 eyes (38.4%) in the open-globe group and better than 20/200 in 36
      eyes (53%) and 20/40 or better in 15 eyes (22.4%) in the closed-globe group. The
      differences between the groups were not significant (P=.143). Of all eyes, 214
      (61.3%) achieved a final CDVA of better than 20/200 and 123 eyes (35.3%), of
      20/40 or better. CONCLUSION: The OTS was a reliable predictor of the final visual
      outcome in cases of pediatric traumatic cataract.

PMID- 22624895
TI  - Comparison of anterior ocular biometry between optical low-coherence
      reflectometry and anterior segment optical coherence tomography in an adult
      Chinese population.
AB  - PURPOSE: To evaluate the agreement between optical low-coherence reflectometry
      (OLCR) and anterior segment optical coherence tomography (AS-OCT) for biometry of
      the anterior segment. SETTING: State Key Laboratory of Ophthalmology, Zhongshan
      Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. DESIGN: Evaluation
      of diagnostic technology. METHODS: A series of OLCR (Lenstar LS 900) and AS-OCT
      measurements of the anterior segment were taken for consecutive subjects aged 35
      years and older in a population-based study. The differences and correlations
      between the 2 methods of ocular biometry were assessed. Agreement was calculated
      as the 95% limits of agreement (LoA). RESULTS: The mean age of the 776 subjects
      was 55.2 years +/- 12.0 (SD); 54.6% were women. The mean central corneal
      thickness (CCT) was smaller with OLCR than with AS-OCT (537.84 +/- 31.46 MUm
      versus 559.39 +/- 32.02 MUm) as was anterior chamber depth (ACD) (2.60 +/- 0.37
      mm versus 2.72 +/- 0.37 mm) and anterior chamber width (ACW) (11.76 +/- 0.47 mm
      versus 12.04 +/- 0.55 mm) (all P<.001). The 95% LoA between the 2 instruments
      were -44.80 to 1.71 MUm for CCT, -0.17 to -0.06 mm for ACD, and -1.28 to 0.72 mm
      for ACW. CONCLUSION: Optical low-coherence reflectometry and AS-OCT yielded
      potentially interchangeable ACD measurements, while the CCT and ACW measurements
      acquired by the 2 devices showed clinically significant differences.

PMID- 22624896
TI  - Visual outcomes with a single-optic accommodating intraocular lens and a low
      addition-power rotational asymmetric multifocal intraocular lens.
AB  - PURPOSE: To compare the visual outcomes and intraocular optical quality in
      patients with a low-addition (add) power multifocal refractive intraocular lens
      (IOL) with rotational asymmetry and a single-optic accommodating IOL. SETTING:
      Vissum Instituto Oftalmologico de Alicante, Miguel Hernandez University,
      Alicante, Spain. DESIGN: Prospective comparative nonrandomized consecutive case
      series. METHODS: Consecutive cataract patients had implantation of a low-add
      power refractive multifocal IOL with rotational asymmetry (Lentis-Mplus LS-312
      MF15) (multifocal group) or a single-optic accommodating IOL (Crystalens HD)
      (accommodating group). Distance and near visual acuities were evaluated. Ocular
      optical quality, intraocular aberrations, defocus curve, and contrast sensitivity
      were evaluated postoperatively. RESULTS: Of the 66 eyes (40 patients; age 61 to
      81 years), 31 were in the multifocal group and 35 were in the accommodating
      group. Postoperatively, both groups had a significant improvement in the
      uncorrected and corrected distance visual acuities and uncorrected (UNVA) and
      corrected near (CNVA) near visual acuities (P <.01). Distance-corrected near
      visual acuity was significantly better in the multifocal group postoperatively (P
      <=.04). No significant differences in UNVA and CNVA were detected postoperatively
      (P >=.09). In the defocus curve, the multifocal group had significantly better
      visual acuities at several defocus levels. The accommodating group had better
      contrast sensitivity under photopic conditions at all spatial frequencies (P
      <=.04). The multifocal group had significantly higher postoperative intraocular
      tilt (P <.01). CONCLUSIONS: Both IOLs restored distance vision. The refractive
      multifocal IOL provided better near visual rehabilitation.

PMID- 22624897
TI  - Sulcus anatomy and diameter in pseudophakic eyes and correlation with biometric
      data: evaluation with a 50 MHz ultrasound biomicroscope.
AB  - PURPOSE: To evaluate the sulcus anatomy and possible correlations between sulcus
      diameter and white-to-white (WTW) diameter in pseudophakic eyes, data that may be
      important in the stability of add-on intraocular lenses (IOLs). SETTING:
      University Eye Hospital, Tuebingen, Germany. DESIGN: Case series. METHODS: In
      pseudophakic eyes, the axial length (AL) and horizontal WTW were measured by the
      IOLMaster device. Cross-sectional images were obtained with a 50 MHz ultrasound
      biomicroscope on the 4 meridians: vertical, horizontal (180 degrees), temporal
      oblique, and nasal oblique. Sulcus-to-sulcus (STS), angle-to-angle (ATA), and
      sclera-to-sclera (ScTSc) diameters were measured. The IOL optic diameter (6.0 mm)
      served as a control. To test reliability, optic measurements were repeated 5
      times in a subset of eyes. RESULTS: The vertical ATA and STS diameters were
      statistically significantly larger than the horizontal diameter (P=.0328 and
      P=.0216, respectively). There was no statistically significant difference in
      ScTSc diameters. A weak correlation was found between WTW and horizontal ATA (r =
      0.5766, P<.0001) and between WTW and horizontal STS (r = 0.5040, P=.0002). No
      correlation was found between WTW and horizontal ScTSc (r = 0.2217, P=.1217).
      CONCLUSIONS: The sulcus anatomy had a vertical oval shape with the vertical
      meridian being the largest, but it also had variation in the direction of the
      largest meridian. The WTW measurements showed a weak correlation with STS. In
      pseudophakic eyes, Soemmerring ring or a bulky haptic may affect the ciliary
      sulcus anatomy.

PMID- 22624898
TI  - Cox proportional hazards model of myopic regression for laser in situ
      keratomileusis flap creation with a femtosecond laser and with a mechanical
      microkeratome.
AB  - PURPOSE: To compare predictive factors for postoperative myopic regression
      between laser in situ keratomileusis (LASIK) with a femtosecond laser and LASIK
      with a mechanical microkeratome. SETTING: Nobel Eye Clinic, Taipei, Taiwan.
      DESIGN: Retrospective comparative study. METHOD: Refractive outcomes were
      recorded 1 day, 1 week, and 1, 3, 6, 9, and 12 months after LASIK. A Cox
      proportional hazards model was used to evaluate the impact of the 2 flap-creating
      methods and other covariates on postoperative myopic regression. RESULTS: The
      femtosecond group comprised 409 eyes and the mechanical microkeratome group, 377
      eyes. For both methods, significant predictors for myopic regression after LASIK
      included preoperative manifest spherical equivalent (P=.0001) and central corneal
      thickness (P=.027). Laser in situ keratomileusis with a mechanical microkeratome
      had a higher probability of postoperative myopic regression than LASIK with a
      femtosecond laser (P=.0002). After adjusting for other covariates in the Cox
      proportional hazards model, the cumulative risk for myopic regression with a
      mechanical microkeratome was higher than with a femtosecond laser 12 months
      postoperatively (P=.0002). With the definition of myopic regression as a myopic
      shift of 0.50 diopter (D) or more and residual myopia of -0.50 D or less, the
      risk estimate based on the mean covariates in all eyes in the femtosecond group
      and mechanical microkeratome group at 12 months was 43.6% and 66.9%,
      respectively. CONCLUSION: Laser in situ keratomileusis with a mechanical
      microkeratome had a higher risk for myopic regression than LASIK with a
      femtosecond laser through 12 months postoperatively.

PMID- 22624899
TI  - Refractive and topographic results of benzalkonium chloride-assisted
      transepithelial crosslinking.
AB  - PURPOSE: To evaluate the effect of benzalkonium chloride-assisted (BAC)
      transepithelial collagen crosslinking (CXL) in eyes with progressive keratoconus
      and a minimum follow-up of 6 months. SETTING: Department of Ophthalmology,
      Antwerp University Hospital, Antwerp, Belgium. DESIGN: Cohort study. METHODS:
      Eyes with progressive keratoconus had CXL treatment without epithelial
      debridement. The standard CXL irradiation was preceded by instillation of
      proparacaine drops 0.5% preserved with BAC 0.005% every 5 minutes for 30 minutes.
      Selected parameters of refraction assessed by Placido disk (Eyesys) and
      Scheimpflug (Pentacam) examinations were compared before CXL and after CXL at 6,
      12, and 18 months. RESULTS: The study enrolled 53 eyes of 38 patients. Sphere,
      cylinder, as well as maximum keratometry (K max) simulated K values (steep, flat,
      astigmatism), and refractive power values (steep, flat, astigmatism) measured
      using the Placido disk device remained stable over the 18-month follow-up. Only
      corrected distance visual acuity showed a statistically significant improvement
      at 6 months and 12 months. The Scheimpflug device measurements of maximum K and
      pachymetry at the thinnest point showed statistically significant progression
      throughout the study. No patient developed corneal haze or other complications.
      CONCLUSION: Transepithelial CXL using proparacaine drops 0.5% preserved with BAC
      0.005% was less effective than standard CXL in stabilizing progressive
      keratoconus.

PMID- 22624900
TI  - Intrastromal corneal ring segment implantation to correct astigmatism after
      penetrating keratoplasty.
AB  - PURPOSE: To evaluate the clinical outcomes of implantation of Ferrara
      intrastromal corneal ring segments (ICRS) in patients with astigmatism after
      penetrating keratoplasty (PKP). SETTING: Private clinic, Belo Horizonte, Brazil.
      DESIGN: Retrospective consecutive case series. METHODS: Chart records of post-PKP
      patients who had ICRS implantation from May 2005 to September 2009 were
      retrospectively reviewed. The following parameters were studied: corrected
      distance visual acuity (CDVA), keratometry (K) values, spherical equivalent (SE),
      spherical refractive error, corneal topographic astigmatism, minimum K, and
      maximum K. RESULTS: The study evaluated 59 eyes (54 patients). The mean CDVA
      (logMAR) improved from 0.45 +/- 0.17 (SD) (range 0.18 to 1.00) to 0.30 +/- 0.17
      (range 0.00 to 1.00). The mean SE was -6.34 +/- 3.40 diopters (D) (range 0.37 to 
      16.50 D) preoperatively and -2.66 +/- 2.52 D (range 0.87 to -10.50 D)
      postoperatively. The mean spherical refractive error decreased from -7.10 +/-
      3.07 D (range 2.15 to 16.68 D) preoperatively to -3.46 +/- 2.05 D (range 0.88 to
      10.79 D) postoperatively. No patient lost visual acuity. The mean corneal
      topographic astigmatism decreased from 3.37 +/- 1.51 D preoperatively to 1.69 +/-
      1.04 D postoperatively. The mean maximum K value decreased from 48.09 +/- 2.56 D
      to 44.17 +/- 2.67 D and the mean minimum K value, from 44.90 +/- 2.54 D to 42.46
      +/- 2.63 D. All changes were statistically significant (P<.0001). CONCLUSION:
      Intrastromal corneal ring segments effectively reduced corneal cylinder in
      patients with astigmatism after PKP.

PMID- 22624901
TI  - Laser in situ keratomileusis to manage refractive errors after deep anterior
      lamellar keratoplasty.
AB  - PURPOSE: To analyze the visual and refractive outcomes of laser in situ
      keratomileusis (LASIK) after deep anterior lamellar keratoplasty (DALK) for
      keratoconus. SETTING: Haydarpasa Numune Education and Research Hospital,
      Ophthalmology Clinic, Istanbul, Turkey. DESIGN: Cohort study. METHODS: Patients
      with compound myopic astigmatism after DALK and a spherical equivalent (SE)
      between -2.50 diopters (D) and -8.00 D had LASIK as a single-step procedure,
      correcting the manifest refraction error. The visual and refractive results at 1
      month, 3 months, and the last follow-up were compared with preoperative values.
      RESULTS: The mean follow-up was 11.17 months +/- 3.61 (SD). The mean manifest
      refraction SE (MRSE) and autorefractometer measurements and the
      autokeratorefractometer and corneal topography keratometry readings decreased
      significantly from preoperatively to 1 month postoperatively (P<.01) but did not
      change significantly thereafter (P>.05). Preoperatively, the mean uncorrected
      (UDVA) and corrected (CDVA) distance visual acuities were 0.21 +/- 0.08 and 0.73
      +/- 0.08, respectively; postoperatively, the means were 0.73 +/- 0.10 and 0.98 +/
      0.05, respectively. All eyes achieved a postoperative UDVA better than 0.5. No
      eye lost CDVA lines. The safety index was 1.34. The mean MRSE was -5.18 +/- 1.74
      D preoperatively and -1.05 +/- 0.64 D postoperatively (P<.01). Postoperatively,
      11 eyes (91.67%) were within +/- 2.00 D of the SE, 8 (6.67%) were within +/- 1.00
      D, and 5 (41.67%) were within +/- 0.50 D. No complications were encountered.
      CONCLUSION: Treatment of post-DALK keratoconus patients with LASIK to correct
      manifest refraction error seems to be a viable option.

PMID- 22624902
TI  - Photorefractive keratectomy with mitomycin-C for the combined treatment of myopia
      and subepithelial infiltrates after epidemic keratoconjunctivitis.
AB  - PURPOSE: To report the use of photorefractive keratectomy (PRK) with mitomycin-C
      (MMC) to treat concomitant myopia and visually significant infiltrates associated
      with epidemic keratoconjunctivitis (EKC). SETTING: Ophthalmic Consultants of Long
      Island, Nassau University, Long Island, New York, USA. DESIGN: Interventional
      case series. METHODS: Consecutive patients with myopia and recalcitrant
      subepithelial infiltrates after EKC were treated with custom wavefront PRK (Visx
      S4 IR) and MMC with a target of emmetropia in all cases. RESULTS: The study
      evaluated 6 eyes of 3 patients. One year after treatment, all eyes attained an
      uncorrected distance visual acuity of 20/20 or better. There was no recurrence of
      infiltrates within the ablation zone in any eye. CONCLUSION: The use of topical
      MMC in conjunction with PRK to treat subepithelial infiltrates due to EKC
      provided good visual and refractive results.

PMID- 22624903
TI  - Long-term comparison of laser in situ keratomileusis versus laser surface
      ablation in corneas thinner than 470 MUm.
AB  - PURPOSE: To compare long-term refractive and visual outcomes of laser in situ
      keratomileusis (LASIK) and laser surface ablation in eyes with corneas thinner
      than 470 MUm. SETTING: Private clinics, Spain. DESIGN: Comparative case series.
      METHODS: The study comprised eyes with myopic error and corneas thinner than 470
      MUm that had at least 2.9 years of postoperative follow-up between September 2001
      and June 2007. The main outcome measures were safety, efficacy, predictability,
      and complications. RESULTS: The mean central corneal thickness was 462.0 MUm
      (range 440 to 469 MUm) in the LASIK group (n = 40) and 458.1 MUm (range 420 to
      469 MUm) in the laser surface ablation group (n = 88). All eyes had normal
      preoperative topography. In the LASIK group after a mean follow-up of 5.1 years
      +/- 1.5 (SD), the safety index was 1.07, efficacy was 0.99, and predictability
      (+/- 1.00 diopter [D]) was 0.93. In the laser surface ablation group after a mean
      follow-up of 4.8 +/- 1.3 years, the safety index was 1.01, efficacy was 0.93, and
      predictability (+/- 1.00 D) was 0.92. The mean residual corneal bed thickness in
      all eyes was 345 +/- 25 MUm (range 270 to 399 MUm). No major complications
      occurred. The safety index was better in the LASIK group than in the laser
      surface ablation group. CONCLUSION: Both techniques were effective, safe, and
      predictable in eyes with corneas thinner than 470 MUm, normal preoperative
      topography, and a residual corneal bed thickness greater than 250 MUm.

PMID- 22624904
TI  - Comparison of front-surface corneal topography and Bowman membrane specular
      topography in keratoconus.
AB  - PURPOSE: To define the contribution of the corneal epithelium in corneal
      topography in keratoconus and discuss the implications regarding combined
      topography-guided photorefractive keratectomy and corneal collagen crosslinking
      (CXL). SETTING: French National Reference Center for Keratoconus, Bordeaux,
      France. DESIGN: Case series. METHODS: Specular topographies were performed before
      and immediately after epithelial removal during conventional CXL surgery in
      patients with keratoconus. RESULTS: The study included 1 eye with forme fruste
      keratoconus, 4 eyes in Krumeich stage I, and 3 eyes in stage II. The mean
      simulated maximum keratometry (K) increased by 2.87 diopters (D) after epithelial
      removal. The mean effective refractive power increased by a mean of 4.01 D and
      the astigmatic refractive power, by a mean of 2.17 D. The difference in mean axis
      deviation was not significant. The mean inferior-superior ratio irregularity
      index increased 1.51 units. All K and refractive readings except astigmatic
      refractive axis were significantly increased after epithelial removal. All
      regularity indices increased significantly without the epithelium. The amplitude
      of variations in K readings made it difficult to predict the refractive changes
      after custom laser photoablation based on epithelial-based topography.
      CONCLUSIONS: The astigmatism refractive axis did not change significantly;
      therefore, this axis could be useful for astigmatic corrections, whereas the
      spherical component would not be useful. Topographic changes after epithelial
      removal can be important but not intuitive in keratoconus eyes. This should be
      considered in custom topography-guided photoablation strategies when attempting
      to correct refractive errors at the time of CXL.

PMID- 22624906
TI  - Comparison of dry-eye disease severity after laser in situ keratomileusis and
      laser-assisted subepithelial keratectomy.
AB  - PURPOSE: To evaluate the effects of laser in situ keratomileusis (LASIK) and
      laser-assisted subepithelial keratectomy (LASEK) on dry-eye disease markers
      including tear osmolarity, Schirmer testing, and the ocular surface disease index
      (OSDI). SETTING: Laser Suite, Mater Private Hospital, Dublin, Ireland. DESIGN:
      Prospective controlled cross-sectional observation study. METHODS: In a single
      center, consecutive eyes that had LASIK or LASEK had dry-eye disease markers
      assessed preoperatively and 3, 6, and 12 months postoperatively. RESULTS: In
      LASIK eyes (n = 50), the mean tear osmolarity was significantly elevated (by
      2.8%) at 12 months (P=.009, Student t test). The mean Schirmer test values were
      not significantly altered postoperatively in either group. The mean OSDI was
      maximum in LASIK eyes at 3 months (mean follow-up 7.2 months +/- 8.2 [SD]) and in
      LASEK eyes (n = 35) preoperatively (mean follow-up 9.1 +/- 9.7 months).
      CONCLUSIONS: There were no significant differences in dry-eye disease markers or
      tear osmolarity between LASIK and LASEK patients at any stage after surgery up to
      1 year. Although tear osmolarity remains one of the highest predictive tests of
      dry eye, it is complementary with other diagnostic criteria in the context of dry
      eye after refractive surgery.

PMID- 22624905
TI  - Visual quality after posterior chamber phakic intraocular lens implantation in
      keratoconus.
AB  - PURPOSE: To quantify image-quality characteristics after correction of refractive
      error with a posterior chamber phakic intraocular lens (PC pIOL) in eyes with
      stable or stabilized keratoconus. SETTING: Narayana Nethralaya Postgraduate
      Institute of Ophthalmology, Bangalore, India. DESIGN: Case series. METHODS: Eyes
      with stable or stabilized keratoconus that had V4 Visian PC pIOL implantation for
      correction of refractive error were evaluated postoperatively for visual-quality
      metrics. RESULTS: Ten eyes of 7 patients had PC pIOL implantation. The
      preoperative mean refractive spherical equivalent of -7.21 diopters (D) +/- 2.25
      (SD) decreased to -0.55 +/- 1.53 D at 6 weeks and -0.44 +/- 1.21 D at 6 months.
      The efficacy index was 0.72 and the safety index, 1.13. The mean modulation
      transfer function (MTF) was 18.96 +/- 14.16 (>= 30 cycles per degree = good), the
      Strehl ratio was 0.11 +/- 0.07 (1 = perfect), and the objective scatter index
      (OSI) was 4.45 +/- 3.29 (>= 1.5 = significant scatter). The MTF correlated
      inversely with secondary coma (P=.026), negative vertical coma (P=.014), and the
      root mean square (RMS) of total aberrations (P=.010) and higher-order aberrations
      (HOAs) (P=.015). The OSI was directly correlated with secondary coma (P=.021),
      secondary trefoil (P=.016), the RMS of total aberrations (P=.032), and HOAs
      (P=.050). CONCLUSION: In keratoconus, the refractive error could be corrected
      with the PC pIOL; however, the associated aberrations had an adverse impact on
      the ultimate visual quality and have to be addressed.

PMID- 22624907
TI  - Objective comparison of 4 nonlongitudinal ultrasound modalities regarding
      efficiency and chatter.
AB  - PURPOSE: To compare efficiency and chatter of Infiniti Ozil with and without
      Intelligent Phacoemulsification (IP) and the Signature Ellips with and without
      FX. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah,
      USA. DESIGN: Experimental study. METHODS: Brunescent 2.0 mm human lens cubes were
      created by an instrument devised for this study. Cubes were tested (10 per test)
      for time of particle removal (efficiency) and for the number of times the lens
      particle bounced off the tip (chatter) at 300 mm Hg and 550 mm Hg, 50% and 100%
      power, and 50% and 100% amplitudes (amplitude for Ozil only). RESULTS: Of the
      ultrasound settings, efficiency varied from a mean of 3.3 seconds +/- 1.4 (SD) to
      50.4 +/- 11.7 seconds and chatter from 0.0 to 52.0 +/- 16.7 bounces per run. The
      Ozil-IP was generally more efficient than the Ozil and the Ellips FX more
      efficient than the Ellips. At optimized values, the Ozil-IP and Ellips-FX were
      similar. In general, efficiency and chatter were better at 550 mm Hg and at 50%
      power. The amplitude effect was complex. Efficiency closely correlated with
      chatter (Pearson r(2) = .31, P<.0001). CONCLUSIONS: Objective comparison of
      phacoemulsification efficiency and chatter found that optimized Ozil-IP and
      Ellips-FX were similar in both parameters and in general, both performed better
      than preceding technology. The study parameters can significantly affect
      efficiency and chatter, which strongly correlate with each other.

PMID- 22624908
TI  - Corneal collagen crosslinking in vitro: inhibited regeneration of human limbal
      epithelial cells after riboflavin-ultraviolet-A exposure.
AB  - PURPOSE: To assess the hypothesis that during corneal crosslinking (CXL)
      treatment, riboflavin and ultraviolet-A (UVA) may have a toxic effect on human
      limbal epithelial cells. SETTING: Center for Eye Research, Department of
      Ophthalmology, Oslo University Hospital Ulleval, Oslo, Norway. DESIGN:
      Experimental study. METHODS: In this vitro study, limbal biopsies from
      corneoscleral rims collected after corneal transplantation were treated with the
      following combinations: riboflavin-UVA, riboflavin only, or UVA only; a control
      group received no treatment. After 3 weeks of cell culture, outgrowth of
      epithelium from the biopsies was evaluated by measuring the area of cell
      expansion and the number of cell layers. The explanted biopsies were analyzed for
      proliferation using immunohistochemistry marker Ki-67 and for apoptosis using the
      terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) assay.
      RESULTS: The mean outgrowth from the biopsies was 2.25 mm(2) +/- 6.90 (SD) in the
      riboflavin-UVA group, 181.4 +/- 94.8 mm(2) in the riboflavin-only group, 128.5 +/
      129.5 mm(2) in the UVA-only group, and 176.2 +/- 114.0 mm(2) in the control
      group. There were no statistically significant between-group differences in the
      number of cell layers except in the riboflavin-UVA group, in which no cells were
      found. Detection of apoptosis with the TUNEL-assay was found in the riboflavin
      UVA group only (4/5 sections). The proliferation marker Ki-67 was positive in
      some sections in all groups. CONCLUSION: Cytotoxicity and reduced cell expansion
      of human limbal epithelial cells occurred after riboflavin-UVA treatment in
      vitro, emphasizing the importance of avoiding riboflavin-UVA on the limbus during
      CXL.

PMID- 22624910
TI  - Bilateral uveitis after phakic intraocular lens implantation and management with
      adalimumab.
AB  - A 25-year-old woman with myopia who had an AC pIOL implantation in the left eye
      and posterior chamber pIOL implantation in the right eye developed bilateral
      granulomatous panuveitis 2 months after the second surgery. Physical examination
      showed bilateral Koeppe and Busacca nodules. Fluorescein angiography showed
      diffuse vascular and retinal pigment epithelial leakage in both eyes. With
      assessment of sympathetic ophthalmia, treatment with a high-dose systemic steroid
      was started. Oral cyclosporine and azathioprine were later added. Because the
      uveitis was not controlled, adalimumab was added. After 6 doses of adalimumab (40
      mg subcutaneously), the uveitis subsided and corticosteroid and other
      immunosuppressive agents were tapered. Refractive AC pIOL implantation should be
      added to the list of intraocular procedures that may induce sympathetic
      ophthalmia. Adalimumab may have a therapeutic role in its management.

PMID- 22624909
TI  - Anterior segment optical coherence tomography in the assessment of postoperative
      intraocular lens optic changes.
AB  - PURPOSE: To evaluate the use of anterior segment optical coherence tomography (AS
      OCT) to assess postoperative intraocular lens (IOL) optic changes. SETTING: John
      A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN:
      Experimental study. METHODS: Intraocular lenses explanted because of various
      complications were used, including poly(methyl methacrylate) (PMMA) IOLs with
      snowflake degeneration, hydrophilic acrylic IOLs with calcification, a silicone
      IOL with calcification from an eye with asteroid hyalosis, and hydrophobic
      acrylic IOLs explanted because of decentration, subluxation, or uveitis-glaucoma
      hyphema syndrome. After gross and light microscopy, the IOLs were examined in the
      dry and hydrated states using AS-OCT. Selected hydrophilic acrylic IOLs were
      stained for calcium. In-the-bag IOLs in pseudophakic cadaver eyes were also
      evaluated by AS-OCT before and after explantation to confirm correspondence with
      the clinical situation. RESULTS: Intraoptic changes, such as snowflake lesions in
      PMMA IOLs, calcification in hydrophilic acrylic IOLs, and glistenings in
      hydrophobic acrylic IOLs, could be imaged by AS-OCT. The method was also helpful
      in analyzing the location and density. However, in cases of more superficial
      changes, unless the lesions/deposits were present on the optic surface with an
      extension to the optic substance of at least 0.1 mm, they could not be clearly
      differentiated from the overall outline of the IOL surface. CONCLUSIONS: Anterior
      segment OCT may be helpful in assessing the presence, location, and density of
      intraoptic changes, avoiding a misdiagnosis of IOL opacification and the
      performance of unnecessary procedures, such as posterior capsulotomy or
      vitrectomy.

PMID- 22624911
TI  - Safety of an artificial iris in a phakic eye.
AB  - This case report describes the one-year results of the implantation of a
      sectorial and foldable artificial iris in a phakic eye. To our knowledge, this is
      the first such report with a follow-up of 1 year. No perioperative or
      postoperative complications were seen. Corrected distance visual acuity remained
      unchanged (left eye, 1.5/10), the subjective complaints of glare and photophobia
      improved considerably, and the patient was very satisfied with the aesthetic
      result.

PMID- 22624912
TI  - Light-adjustable intraocular lens in post-LASIK and post-traumatic cataract
      patient.
AB  - The case illustrates the use of a light-adjustable intraocular lens (IOL) in a
      patient who had had refractive surgery and developed blunt trauma with resultant
      flap damage and traumatic cataract. Consistent with early reports of the light
      adjustable IOL, which show positive results in non-LASIK eyes, this case suggests
      that the light-adjustable IOL may have similar benefits in the post-LASIK eye and
      other complex situations.

PMID- 22624913
TI  - Intraocular lens fixation with a 30-gauge injectable shape-memory alloy clip in a
      porcine eye.

PMID- 22624914
TI  - Surgical step to facilitate phacoemulsification after Descemet membrane
      endothelial keratoplasty.

PMID- 22624915
TI  - Consultation section. Cataract surgical problem.

PMID- 22624924
TI  - Here's a good tip.

PMID- 22624925
TI  - Bevel tip position and corneal damage during phacoemulsification.

PMID- 22624927
TI  - Bevel-up versus bevel-down phacoemulsification tip.

PMID- 22624928
TI  - Opacification of anterior part of hydrophilic acrylic IOL or a prelenticular
      inflammatory membrane?

PMID- 22624930
TI  - Rotationally asymmetric multifocal intraocular lens.

PMID- 22624932
TI  - India ink intrusion?

PMID- 22624934
TI  - Struma ovarii and the thyroid surgeon.
AB  - INTRODUCTION: Struma ovarii is a rare, monodermal, ovarian teratoma. The common
      presentation is abdominal, with pelvic mass and pain, traditionally managed by
      gynaecologists. The malignant form is extremely rare and consists of
      differentiated thyroid cancer. It is rare for struma ovarii to present with
      features of hyperthyroidism. We present two unusual cases of struma ovarii and
      discuss the role of the thyroid surgeon in their management. METHODS AND RESULTS:
      The first case involved a 40-year-old woman with a two-month history of swelling
      in the lower abdomen. Investigations revealed a mass arising from the left ovary.
      Surgery revealed a follicular carcinoma arising in a struma ovarii. She underwent
      a total thyroidectomy prior to radio-iodine therapy. The second case involved a
      60-year-old woman who underwent thyroidectomy for thyrotoxicosis. Three months
      post-operatively, she remained thyrotoxic despite stopping thyroxine. A whole
      body radio-iodine scan revealed high uptake in the left ovary. Histological
      analysis of the resected ovary showed benign struma ovarii. CONCLUSION: These two
      cases highlight the diagnostic and therapeutic role of thyroid surgeons in the
      management of benign and malignant forms of struma ovarii.

PMID- 22624935
TI  - Getting past getting by: training culturally and linguistically competent
      bilingual physicians.

PMID- 22624944
TI  - Conservation in a cup of water: estimating biodiversity and population abundance
      from environmental DNA.
AB  - Three mantras often guide species and ecosystem management: (i) for preventing
      invasions by harmful species, 'early detection and rapid response'; (ii) for
      conserving imperilled native species, 'protection of biodiversity hotspots'; and
      (iii) for assessing biosecurity risk, 'an ounce of prevention equals a pound of
      cure.' However, these and other management goals are elusive when traditional
      sampling tools (e.g. netting, traps, electrofishing, visual surveys) have poor
      detection limits, are too slow or are not feasible. One visionary solution is to
      use an organism's DNA in the environment (eDNA), rather than the organism itself,
      as the target of detection. In this issue of Molecular Ecology, Thomsen et al.
      (2012) provide new evidence demonstrating the feasibility of this approach,
      showing that eDNA is an accurate indicator of the presence of an impressively
      diverse set of six aquatic or amphibious taxa including invertebrates,
      amphibians, a fish and a mammal in a wide range of freshwater habitats. They are
      also the first to demonstrate that the abundance of eDNA, as measured by qPCR,
      correlates positively with population abundance estimated with traditional tools.
      Finally, Thomsen et al. (2012) demonstrate that next-generation sequencing of
      eDNA can quantify species richness. Overall, Thomsen et al. (2012) provide a
      revolutionary roadmap for using eDNA for detection of species, estimates of
      relative abundance and quantification of biodiversity.

PMID- 22624945
TI  - Within-genotype epigenetic variation enables broad niche width in a flower living
      yeast.
AB  - Niche theory is one of the central organizing concepts in ecology. Generally,
      this theory defines a given species niche as all of the factors that effect the
      persistence of the species as well as the impact of the species in a given
      location (Hutchinson 1957; Chase 2011). Many studies have argued that phenotypic
      plasticity enhances niche width because plastic responses allow organisms to
      express advantageous phenotypes in a broader range of environments (Bradshaw
      1965; Van Valen 1965; Sultan 2001). Further, species that exploit habitats with
      fine-grained variation, or that form metapopulations, are expected to develop
      broad niche widths through phenotypic plasticity (Sultan & Spencer 2002;
      Baythavong 2011). Although a long history of laboratory, greenhouse and
      reciprocal transplant experiments have provided insight into how plasticity
      contributes to niche width (Pigliucci 2001), recent advances in molecular
      approaches allow for a mechanistic understanding of plasticity at the molecular
      level (Nicotra et al. 2010). In particular, variation in epigenetic effects is a
      potential source of the within-genotype variation that underlies the phenotypic
      plasticity associated with broad niche widths. Epigenetic mechanisms can alter
      gene expression and function without altering DNA sequence (Richards 2006) and
      may be stably transmitted across generations (Jablonka & Raz 2009; Verhoeven et
      al. 2010). Also, epigenetic mechanisms may be an important component of an
      individual's response to the environment (Verhoeven et al. 2010). While these
      ideas are intriguing, few studies have made a clear connection between genome
      wide DNA methylation patterns and phenotypic plasticity (e.g. Bossdorf et al.
      2010). In this issue of Molecular Ecology, Herrera et al. (2012) present a study
      that demonstrates epigenetic changes in genome-wide DNA methylation are causally
      active in a species' ability to exploit resources from a broad range of
      environments and are particularly important in harsh environments.

PMID- 22624946
TI  - Population studies of native grass-endophyte symbioses provide clues for the
      roles of host jumps and hybridization in driving their evolution.
AB  - Fungal endophytes in the genera Epichloe and Neotyphodium, collectively termed
      the epichloae, have fascinated biologists for decades. These intriguing fungi,
      also referred to as 'class 1 or clavicipitaceous endophytes', spend the large
      majority, or even their entire life cycle, within the tissues of their cool
      season grass hosts without eliciting any symptoms of infection. While all
      epichloae reside within the intercellular spaces of aboveground vegetative grass
      tissues, the species at the symbiotic extreme are known as Neotyphodium, and the
      intimacy of their interaction extends to the reproductive (flowering) stage. At
      this point, fungal filaments (hyphae) nondestructively invade the developing
      ovaries of their host and are incorporated into perfectly viable, healthy seeds.
      Thus, these endophytes live solely within the tissues of their host plants and
      are transmitted maternally from generation to generation. A second life history
      characteristic of interest is that while all Epichloe and some Neotyphodium
      species are haploid, a great many of the strictly seed-transmitted Neotyphodium
      spp. are interspecific hybrids. This phenomenon may be critical for the success
      of these symbioses over longer spans of evolutionary time and will be discussed
      in greater detail below. A third characteristic, and one of the primary reasons
      these grass endophytes have received so much attention over the last three
      decades, is the strong mutualistic nature these relationships often exhibit. In
      exchange for photosynthetically derived carbon, the endophytes protect their cool
      season grass hosts from grazing herbivores and a variety of abiotic stresses. It
      has been hypothesized that these three biological phenomena are related (Schardl
      & Craven 2003), perhaps with the former two driving the third, and it is here
      that the recent article in Molecular Ecology entitled 'Genetic diversity in
      epichloid endophytes of Hordelymus europaeus suggests repeated host jumps and
      interspecific hybridizations', by Oberhofer & Leuchtmann (2012), provides
      critical clues to linking these traits together. While the large majority of
      studies have focused on documenting the ever-increasing list of mutualistic
      qualities attributed to these fungi, very few have taken an exhaustive population
      level approach to document plant and endophyte genotypes within a naturally
      occurring system (Faeth et al. 2010; Jani et al. 2010; Tintjer & Rudgers 2006).
      Such information is crucial to more fully elucidate the factors shaping grass
      endophyte symbioses and those often driving these relationships to mutualistic
      extremes.

PMID- 22624948
TI  - Retroperitoneal laparoendoscopic single-site ureterolithotomy and
      ureteroureterostomy for retrocaval ureter with ureteral calculus: first case
      report.
AB  - A 53-year-old man presented with a 6-month history of intermittent right flank
      pain. Radiological imaging confirmed the diagnosis of retrocaval ureter (RCU) and
      ureteral calculus. Retroperitoneal laparoendoscopic single-site surgery (LESS)
      ureterolithotomy and ureteroureterostomy was successfully performed. The
      operative time was 185 min and the blood loss was approximately 20 ml. The
      patient's postoperative course was uneventful. Postoperative analgesia was not
      needed. The patient was discharged on the third postoperative day. The drain and
      double-J stent were respectively removed at 1 and 8 weeks postoperatively. At the
      3-month follow-up, nuclear scan showed no evidence of obstruction of the right
      kidney and the patient also remained symptom free. It may be concluded that
      retroperitoneal LESS repair for RCU is a feasible and safe procedure, which can
      be considered as a option for the management of RCU even if it is complicated by
      the presence of a ureteral calculus.

PMID- 22624947
TI  - Isopeptide bonds of the major pilin protein BcpA influence pilus structure and
      bundle formation on the surface of Bacillus cereus.
AB  - Bacillus cereus strains elaborate pili on their surface using a mechanism of
      sortase-mediated cross-linking of major and minor pilus components. Here we used
      a combination of electron microscopy and atomic force microscopy to visualize
      these structures. Pili occur as single, double or higher order assemblies of
      filaments formed from monomers of the major pilin, BcpA, capped by the minor
      pilin, BcpB. Previous studies demonstrated that within assembled pili, four
      domains of BcpA - CNA(1), CNA(2), XNA and CNA(3) - each acquire intramolecular
      lysine-asparagine isopeptide bonds formed via catalytic glutamic acid or aspartic
      acid residues. Here we showed that mutants unable to form the intramolecular
      isopeptide bonds in the CNA(2) or CNA(3) domains retain the ability to form pilus
      bundles. A mutant lacking the CNA(1) isopeptide bond assembled deformed pilin
      subunits that failed to associate as bundles. X-ray crystallography revealed that
      the BcpA variant Asp(312) Ala, lacking an aspartyl catalyst, did not generate the
      isopeptide bond within the jelly-roll structure of XNA. The Asp(312) Ala mutant
      was also unable to form bundles and promoted the assembly of deformed pili. Thus,
      structural integrity of the CNA(1) and XNA domains are determinants for the
      association of pili into higher order bundle structures and determine native
      pilus structure.

PMID- 22624949
TI  - Exhaled NO is a poor marker of asthma control in children with a reported use of
      asthma medication: a pharmacy-based study.
AB  - BACKGROUND: A high fraction of nitric oxide in exhaled breath (FeNO) has been
      suggested to be a marker of ongoing airway inflammation and poorly controlled
      disease in asthma. The usefulness of FeNO to monitor asthma control is still
      debated today. AIM: To assess the validity of FeNO as a marker of asthma control
      in children with reported use of asthma medication. METHODS: Fraction of nitric
      oxide in exhaled breath was measured in 601 children (aged 4-12 yr) with reported
      use of asthma medication in the past 6 months and in 63 healthy non-asthmatic
      children (aged 5-12). Asthma control was assessed by the Asthma Control
      Questionnaire (ACQ). A receiver-operator characteristics (ROC) curve was
      generated to assess the accuracy of FeNO as a marker for asthma control. Logistic
      regression analysis was used to study whether clinical, healthcare, medication,
      and environmental factors are associated with high FeNO levels (>25 ppb).
      RESULTS: Fraction of nitric oxide in exhaled breath had a poor accuracy to
      discriminate well-controlled from not well-controlled asthma [area under the ROC
      curve: 0.56 (95% CI: 0.52-0.61, p = 0.008)]. In addition, high FeNO (>25 ppb) was
      associated with lower medication adherence rates (OR: 0.4; 95% CI 0.3-0.6), fewer
      antibiotic courses in the past year (OR: 0.6; 95% CI: 0.4-0.9), fewer leukotriene
      antagonists use in the past year (OR: 0.4; 95% CI: 0.2-0.9), and fewer visits to
      a (pulmonary) pediatrician (OR: 0.6; 95% CI: 0.4-0.9). Children living in a non
      urban environment had more often high FeNO levels (OR: 1.7; 95% CI: 1.1-2.6).
      CONCLUSION: High FeNO is a poor marker of asthma control in children with
      reported use of asthma medication. Various other factors, including medication
      adherence and medication use, are associated with increased FeNO levels.

PMID- 22624950
TI  - Arabidopsis acetyl-amido synthetase GH3.5 involvement in camalexin biosynthesis
      through conjugation of indole-3-carboxylic acid and cysteine and upregulation of
      camalexin biosynthesis genes.
AB  - Camalexin (3-thiazol-2'-yl-indole) is the major phytoalexin found in Arabidopsis
      thaliana. Several key intermediates and corresponding enzymes have been
      identified in camalexin biosynthesis through mutant screening and biochemical
      experiments. Camalexin is formed when indole-3-acetonitrile (IAN) is catalyzed by
      the cytochrome P450 monooxygenase CYP71A13. Here, we demonstrate that the
      Arabidopsis GH3.5 protein, a multifunctional acetyl-amido synthetase, is involved
      in camalexin biosynthesis via conjugating indole-3-carboxylic acid (ICA) and
      cysteine (Cys) and regulating camalexin biosynthesis genes. Camalexin levels were
      increased in the activation-tagged mutant gh3.5-1D in both Col-0 and cyp71A13-2
      mutant backgrounds after pathogen infection. The recombinant GH3.5 protein
      catalyzed the conjugation of ICA and Cys to form a possible intermediate indole-3
      acyl-cysteinate (ICA(Cys)) in vitro. In support of the in vitro reaction, feeding
      with ICA and Cys increased camalexin levels in Col-0 and gh3.5-1D.
      Dihydrocamalexic acid (DHCA), the precursor of camalexin and the substrate for
      PAD3, was accumulated in gh3.5-1D/pad3-1, suggesting that ICA(Cys) could be an
      additional precursor of DHCA for camalexin biosynthesis. Furthermore, expression
      of the major camalexin biosynthesis genes CYP79B2, CYP71A12, CYP71A13 and PAD3
      was strongly induced in gh3.5-1D. Our study suggests that GH3.5 is involved in
      camalexin biosynthesis through direct catalyzation of the formation of ICA(Cys),
      and upregulation of the major biosynthetic pathway genes.

PMID- 22624951
TI  - Interactions between occlusion and human brain function activities.
AB  - There are few review articles in the area of human research that focus on the
      interactions between occlusion and brain function. This systematic review
      discusses the effect of occlusion on the health of the entire body with a focus
      on brain function. Available relevant articles in English from 1999 to 2011 were
      assessed in an online database and as hard copies in libraries. The selected 19
      articles were classified into the following five categories: chewing and tongue
      movements, clenching and grinding, occlusal splints and occlusal interference,
      prosthetic rehabilitation, and pain and stimulation. The relationships between
      the brain activity observed in the motor and sensory cortices and movements of
      the oral and maxillofacial area, such as those produced by gum chewing, tapping
      and clenching, were investigated. It was found that the sensorimotor cortex was
      also affected by the placement of the occlusal interference devices, splints and
      implant prostheses. Brain activity may change depending on the strength of the
      movements in the oral and maxillofacial area. Therefore, mastication and other
      movements stimulate the activity in the cerebral cortex and may be helpful in
      preventing degradation of a brain function. However, these findings must be
      verified by evidence gathered from more subjects.

PMID- 22624952
TI  - Estimation of binding constants of peptide nucleic acid and secondary-structured
      DNA by affinity capillary electrophoresis.
AB  - An affinity capillary electrophoresis method was developed to determine a binding
      constant between a peptide nucleic acid (PNA) and a hairpin-structured DNA. A
      diblock copolymer composed of PNA and polyethylene glycol (PEG) was synthesized
      as a novel affinity probe. The base sequence of the probe's PNA segment was
      complementary to a hairpin-structured region of a 60-base single-stranded DNA
      (ssDNA). Upon applying a voltage, the DNA hairpin migrated slowly compared to a
      random sequence ssDNA in the presence of the PNA probe. This retardation was
      induced by strand invasion of the PNA into the DNA hairpin to form a hybridized
      complex, where the PEG segment received a large amount of hydrodynamic friction
      during electrophoresis. The binding constant between the PNA probe and the DNA
      hairpin was easily determined by mobility analysis. This simple method would be
      potentially beneficial in studying binding behaviors of various artificial
      nucleotides to natural DNA or RNA.

PMID- 22624953
TI  - Sleep/wake estimation using only anterior tibialis electromyography data.
AB  - BACKGROUND: In sleep efficiency monitoring system, actigraphy is the simplest and
      most commonly used device. However, low specificity to wakefulness of actigraphy
      was revealed in previous studies. In this study, we assumed that sleep/wake
      estimation using actigraphy and electromyography (EMG) signals would show
      different patterns. Furthermore, each EMG pattern in two states (sleep, wake
      during sleep) was analysed. Finally, we proposed two types of method for the
      estimation of sleep/wake patterns using only EMG signals from anterior tibialis
      muscles and the results were compared with PSG data. METHODS: Seven healthy
      subjects and five patients (2 obstructive sleep apnea, 3 periodic limb movement
      disorder) participated in this study. Night time polysomnography (PSG) recordings
      were conducted, and electrooculogram, EMG, electroencephalogram,
      electrocardiogram, and respiration data were collected. Time domain analysis and
      frequency domain analysis were applied to estimate the sleep/wake patterns. Each
      method was based on changes in amplitude or spectrum (total power) of anterior
      tibialis electromyography signals during the transition from the sleep state to
      the wake state. To obtain the results, leave-one-out-cross-validation technique
      was adopted. RESULTS: Total sleep time of the each group was about 8 hours. For
      healthy subjects, the mean epoch-by-epoch results between time domain analysis
      and PSG data were 99%, 71%, 80% and 0.64 (sensitivity, specificity, accuracy and
      kappa value), respectively. For frequency domain analysis, the corresponding
      values were 99%, 73%, 81% and 0.67, respectively. Absolute and relative
      differences between sleep efficiency index from PSG and our methods were 0.8 and
      0.8% (for frequency domain analysis). In patients with sleep-related disorder,
      our proposed methods revealed the substantial agreement (kappa > 0.61) for OSA
      patients and moderate or fair agreement for PLMD patients. CONCLUSIONS: The
      results of our proposed methods were comparable to those of PSG. The time and
      frequency domain analyses showed the similar sleep/wake estimation performance.

PMID- 22624955
TI  - Flavonoids and saponins from Zizyphus incurva.
AB  - A new flavonol triglycoside, myricetin-3-O-[beta-xylopyranosyl-(1-2)-alpha
      rhamnopyranoside]-4'-O-alpha -rhamnopyranoside, named as bayarin (1), was
      isolated from the aerial parts of Zizyphus incurva Roxb. (Rhamnaceae) along with
      eight known compounds: six flavonoids and two saponins. All of these compounds
      were isolated for the first time from this plant. Structures of these compounds
      were elucidated on the basis of spectroscopic data.

PMID- 22624956
TI  - Liminality and transfer to adult services: a qualitative investigation involving
      young people with cystic fibrosis.
AB  - BACKGROUND: Moving to adult care can be challenging for adolescents with a long
      term condition; if not managed well it may result in non-adherence, failure to
      attend appointments and a decline in health post-transfer. Life expectancy for
      those with cystic fibrosis has improved considerably in recent decades. This
      patient group was selected as an exemplar for thinking about the movement of care
      from paediatric to adult services. OBJECTIVES: To explore young people's
      experience of transferring. DESIGN: A qualitative descriptive methodology,
      involving semi-structured interviews. SETTING: One adult cystic fibrosis unit in
      the United Kingdom. PARTICIPANTS: 19 patients (12=male) who had moved to the
      study site no more than 12 months prior to data collection, which took place
      between October 2010 and February 2011. METHODS: Interviews were conducted face
      to-face, by telephone or email. Framework analysis was applied to interview
      transcripts. RESULTS: Data suggested transfer was a period of flux, during which
      participants progressed from a service that was relatively prescriptive to one
      that called for autonomy. They appeared to go through three stages during this
      process: fracturing, acclimatising and integrating. The concept of liminality was
      used as a lens to explore data. Liminality describes those on the threshold of a
      new social position and rituals that bring meaning to such change. Rites of
      passage, such as being visited by a member of the adult team and a first
      appointment within this new healthcare setting, were important because they
      allowed for initiation into the workings of the adult unit. However, the absence
      of certain rituals, including a ceremony marking departure from paediatrics,
      might hinder progression towards becoming an adult patient. CONCLUSIONS: The
      concept of liminality proved useful for thinking about data. Additional work
      should explore whether it can be applied to different long-term conditions and if
      initiation rituals vary across services. Nurses could play a role in preparing
      adolescents by assessing their readiness to transfer on a regular basis and
      intervening to address individual needs. This would help with young people's
      shift from a paediatric to adult identity, hopefully preventing them from
      experiencing a prolonged liminal state post-transfer.

PMID- 22624957
TI  - [Laparoscopic treatment of acute gastric volvulus].
AB  - INTRODUCTION: Gastric volvulus is an uncommon clinical condition and is
      associated with type ii-iii hiatal hernias. Its acute presentation constitutes a
      surgical emergency. Despite its low frequency, results of laparoscopic treatment
      have already been published. MATERIAL AND METHODS: A retrospective study was
      performed on all cases diagnosed with gastric volvulus undergoing laparoscopic
      surgery between 1998 and 2010. The surgical technique, the post-operative
      outcome, and the clinical follow-up are described. RESULTS: A total of 10 cases
      were identified, one was a primary gastric volvulus, and the remainder were
      secondary. A laparoscopic anterior gastropexy as the sole procedure was performed
      on 7 patients. A Nissen fundoplication with mesh reinforcement of the crural
      closure was performed on the 3 remaining cases. Postoperative outcome was
      uneventful in 9 patients, with an early start of the diet, and hospital discharge
      between 48-72 h. After a mean follow-up period of 18 months, radiological hernia
      recurrence occurred in one case but recurrence of the volvulus was not observed.
      CONCLUSION: Laparoscopic anterior gastropexy is, in our experience, an effective
      and safe procedure with a low morbidity, for the treatment of acute gastric
      volvulus in patients with high surgical risk.

PMID- 22624958
TI  - Chronic inflammation as predictor of 1-year hospitalization and mortality in
      elderly population.
AB  - BACKGROUND: Systemic low-grade inflammation is thought to be associated with an
      increased risk of adverse clinical outcomes in elderly population. We tested this
      notion with the goal of identifying useful potential biomarkers of 1-year
      hospitalization and mortality in the elderly population. DESIGN: A total of 120
      institutionalized older subjects were enrolled as participants in this study,
      including 90 women and 30 men (ranging in age from 68 to 105 years), selected
      from Santa Teresa nursing home (Oviedo, Spain). We studied functional status,
      morbidity, socio-demographic characteristics and several inflammation and
      inflammation-related markers. RESULTS: The study included 95 non-hospitalized
      participants and 23 participants with at least one hospitalization during 1 year
      (19% of subjects). The study also included 100 survivors and 19 participants who
      died during the 1-year study (16% of subjects). In logistic regression models
      adjusted by age, sex, anti-inflammatory drug use and morbid conditions, high
      levels of interleukin 1 receptor antagonist (IL-1ra) and red blood cell
      distribution width (RDW) were associated with hospitalization and death at 1
      year. Elevated levels of tumour necrosis factor alpha (TNF-alpha) were also
      associated with an increased risk of death at 1 year after adjusting for the same
      potential confounders. Multivariate logistic regression models showed that
      elevated serum levels of IL-1ra were intimately associated with 1-year subsequent
      hospitalization and mortality in aged subjects after adjusting for age, sex, anti
      inflammatory drug use and morbid conditions. CONCLUSIONS: Current data suggest
      that IL-1ra is a predictor of 1-year hospitalization and mortality in the elderly
      population.

PMID- 22624959
TI  - Mechanisms of Fc receptor and dectin-1 activation for phagocytosis.
AB  - Phagocytosis is a key cellular process, both during homeostasis and upon
      infection or tissue damage. Receptors on the surface of professional phagocytic
      cells bind to target particles either directly or through opsonizing ligands, and
      trigger actin-mediated ingestion of the particles. The process must be carefully
      controlled to ensure that phagocytosis is triggered efficiently and specifically,
      and that the antimicrobial cytotoxic responses that often accompany it are
      initiated only when required. In this review, we will describe and compare the
      molecular mechanisms that regulate phagocytosis triggered by Fcgamma receptors,
      which mediate the uptake of immunoglobulin G-opsonized targets, and Dectin-1,
      which is responsible for internalization of fungi with exposed cell wall beta
      glucan. We will examine how these receptors detect their ligands, how signal
      transduction is initiated and regulated, and how internalization is instructed to
      achieve rapid and yet controlled uptake of their targets.

PMID- 22624960
TI  - AM-8553: a novel MDM2 inhibitor with a promising outlook for potential clinical
      development.

PMID- 22624961
TI  - High frequency of false-positive reactions in attempted patch testing with
      acrylate/methacrylate mixes.
AB  - BACKGROUND: Although acrylate/methacrylate allergy has been frequently reported,
      until now patch testing with this group of allergens has been unwieldy, requiring
      the application of large supplementary series in most centres. OBJECTIVES: To
      formulate and evaluate two mixes of acrylate/methacrylate allergens in three
      centres (Malmo, Singapore, and Leuven). PATIENTS/MATERIALS/METHODS: All patients
      tested with the baseline series during the study period were also patch tested
      with the mixes. Mix 1 consisted of: triethyleneglycol diacrylate (TREGDA) 0.1%
      wt/wt, 2-hydroxyethyl methacrylate (2-HEMA) 1.0% wt/wt and ethyleneglycol
      dimethacrylate 1.0% wt/wt in petrolatum. Mix 2 consisted of: TREGDA 0.1% wt/wt
      and 2-HEMA 2.0% wt/wt in pet. The separate components of the two mixes were also
      tested simultaneously. RESULTS: There were 25 (5 males; 20 females) positive
      reactions to mix 1 with 16 in Malmo, 8 in Singapore, and 1 in Leuven. Positive
      reactions to mix 2 were seen only in Malmo, in 8 female patients. Thus, the
      positive reaction rate for mix 1 was 8.3% overall (Malmo 7.7%, Singapore 18.6%,
      and Leuven 2.1%), and that for mix 2 was 2.7% overall (Malmo 3.8%, Singapore 0%,
      and Leuven 0%). Of the 16 positive reactions to mix 1 in Malmo, only 4 were
      considered to be true allergic reactions, as the component allergen testing gave
      totally negative results in 12/16. For mix 2, only 3/8 positive reactions were
      considered to be true allergic reactions, as the component testing was negative
      in 5/8. Many doubtful (10-20%) and positive but non-allergic reactions were
      recorded, leading to early termination of the study. CONCLUSIONS: Although this
      was an unsuccessful attempt to formulate an acrylate/methacrylate mix, our
      experience will be useful for those embarking on future attempts to do this.

PMID- 22624963
TI  - Letter from the editor: Imaging of the aorta.

PMID- 22624962
TI  - Modeling and structural analysis of PA clan serine proteases.
AB  - BACKGROUND: Serine proteases account for over a third of all known proteolytic
      enzymes; they are involved in a variety of physiological processes and are
      classified into clans sharing structural homology. The PA clan of endopeptidases
      is the most abundant and over two thirds of this clan is comprised of the S1
      family of serine proteases, which bear the archetypal trypsin fold and have a
      catalytic triad in the order Histidine, Aspartate, Serine. These proteases have
      been studied in depth and many three dimensional structures have been
      experimentally determined. However, these structures mostly consist of bacterial
      and animal proteases, with a small number of plant and fungal proteases and as
      yet no structures have been determined for protozoa or archaea. The core
      structure and active site geometry of these proteases is of interest for many
      applications. This study investigated the structural properties of different S1
      family serine proteases from a diverse range of taxa using molecular modeling
      techniques. RESULTS: Our predicted models from protozoa, archaea, fungi and
      plants were combined with the experimentally determined structures of 16 S1
      family members and used for analysis of the catalytic core. Amino acid sequences
      were submitted to SWISS-MODEL for homology-based structure prediction or the
      LOOPP server for threading-based structure prediction. Predicted models were
      refined using INSIGHT II and SCRWL and validated against experimental structures.
      Investigation of secondary structures and electrostatic surface potential was
      performed using MOLMOL. The structural geometry of the catalytic core shows clear
      deviations between taxa, but the relative positions of the catalytic triad
      residues were conserved. Some highly conserved residues potentially contributing
      to the stability of the structural core were identified. Evolutionary divergence
      was also exhibited by large variation in secondary structure features outside the
      core, differences in overall amino acid distribution, and unique surface
      electrostatic potential patterns between species. CONCLUSIONS: Encompassing a
      wide range of taxa, our structural analysis provides an evolutionary perspective
      on S1 family serine proteases. Focusing on the common core containing the
      catalytic site of the enzyme, this analysis is beneficial for future molecular
      modeling strategies and structural analysis of serine protease models.

PMID- 22624964
TI  - Imaging of the aorta: embryology and anatomy.
AB  - This review focuses on the embryology and anatomy of the aorta with some imaging
      examples. Dividing the aorta by segments of unique function and embryogenesis
      facilitates organizing the group of potential anomalies encountered. A basic
      understanding of the embryologic development of the aorta and its major branches
      helps in understanding and recognizing typical and atypical anatomic findings.
      Diagnostic imaging of the aorta and its major branches can be accomplished by
      invasive and noninvasive methods, based on the clinical scenario and the age of
      the patient. In this review, computed tomography and magnetic resonance imaging
      examples are emphasized.

PMID- 22624965
TI  - Multidetector computed tomography of congenital anomalies of the thoracic aorta.
AB  - Congenital abnormalities may affect any segment of the thoracic aorta. Their
      clinical presentation is quite variable, and some may require prompt and precise
      diagnosis to avoid complications. Associated cardiovascular comorbidities are
      common, and their presence and type may significantly affect prognosis,
      management, and patient outcome. Nowadays, state-of-the-art multidetector
      computed tomography has replaced invasive angiography in the evaluation of
      patients with suspected aortic disease. With the advent of this technology that
      allows diagnostic scans even in small infants and newborns, radiologists must be
      familiar with anatomy and pathophysiology of these uncommon diseases. The
      embryology, morphology, and imaging findings of these anomalies, divided
      according to their anatomic location, are reviewed.

PMID- 22624966
TI  - Infectious and noninfectious aortitis: cross-sectional imaging findings.
AB  - "Aortitis" is a pathologic term that refers to an abnormal inflammation of the
      aortic wall. A wide spectrum of infectious, inflammatory, and idiopathic
      conditions may result in the development of aortitis. Infectious aortitis may be
      secondary to bacterial, tubercular, syphilitic, and viral pathogens. Although
      Takayasu arteritis and giant cell arteritis are the most common rheumatologic
      causes of aortitis, the other systemic diseases, such as rheumatoid arthritis,
      systemic lupus erythematosus, Behcet disease, and Cogan syndrome, may also be
      associated with aortitis. In addition, aortitis may also occur without any
      systemic diseases or infectious causes (idiopathic). Clinical features of
      aortitis are nonspecific and may include fever, abdominal or chest pain, and
      vascular insufficiency. Patients may have elevated serum levels of acute phase
      reactants. A high index of clinical suspicion is always needed for the diagnosis
      of aortitis in a timely manner. Cross-sectional imaging techniques, such as
      computed tomographic angiography, magnetic resonance imaging, magnetic resonance
      angiography, and positron emission tomography, are extremely helpful in
      diagnosis, assessing disease activity, treatment planning, and post-treatment
      follow-up. Many of the patients with aortitis may require a multimodality imaging
      approach for appropriate diagnosis. Knowledge of the clinical features and cross
      sectional imaging findings of different types of aortitis permit optimal patient
      management.

PMID- 22624967
TI  - State-of-the-art computed tomography angiography of acute aortic syndrome.
AB  - Acute aortic syndrome refers to a spectrum of acute life-threatening aortic
      abnormalities requiring prompt recognition and treatment. Although underlying
      pathologies are diverse, presenting signs and symptoms are often
      indistinguishable clinically, underscoring the role of imaging to make the
      correct diagnosis. Computed tomography (CT) angiography, a safe and accessible
      imaging modality, is paramount in accurately confirming or excluding critical
      aortic lesions, defining location and extent, and describing associated
      complications. Electrocardiographic gating further improves diagnostic precision
      of CT, providing motion-free 3- and 4-dimensional imaging of the entire aorta.
      This article reviews the imaging spectrum and state-of-the-art CT for patients
      presenting with acute aortic syndrome.

PMID- 22624968
TI  - Computed tomography angiography of thoracic aortic aneurysms.
AB  - Thoracic aortic aneurysms (TAAs) can be life-threatening but often remain
      undiagnosed until a complication occurs or the disease is discovered incidentally
      on imaging studies performed for other purposes. Multidetector-row computed
      tomography angiography has emerged as a useful modality for aortic imaging and
      allows a comprehensive evaluation of TAAs in terms of their morphology, extent,
      amount of thrombus, relationship to adjacent structures, and signs of acute or
      impending rupture. This article reviews the normal anatomy of the thoracic aorta,
      etiology of TAAs, and the spectrum of their imaging appearance. Technical
      considerations for performing and interpreting multidetector-row computed
      tomography angiography of the thoracic aorta will be presented along with the
      role this modality plays in identifying the various complications associated with
      TAAs.

PMID- 22624969
TI  - Thoracic endovascular aortic repair: literature review with emphasis on the role
      of multidetector computed tomography.
AB  - Thoracic endovascular aortic repair (TEVAR) has evolved as an alternative to open
      repair for a range of aortic pathology. The earliest endovascular repairs were
      limited to descending thoracic aortic pathology, but growing experience has
      resulted in the use of stents in the ascending aorta and aortic arch. This review
      presents the current literature pertaining to thoracic endoluminal stent repair,
      with emphasis on the role of intravenous contrast-enhanced multidetector computed
      tomography, the primary cross-sectional imaging modality used in these patients.
      Radiologists play an integral role in patient selection, procedural planning, and
      postprocedural follow-up.

PMID- 22624970
TI  - Aortic tumors.
AB  - Increasing use of cross-sectional studies has resulted in a concomitant increase
      in the number of intravascular and perivascular masses found in patients being
      studied for a multitude of thoracic conditions. As a consequence, there needs to
      be an awareness of the imaging findings of certain unusual abnormalities that
      will help prevent erroneous treatment (eg, anticoagulation) and expedite proper
      therapy. Although the spectrum of conditions that may present as intravascular,
      mural, and extravascular abnormalities in and around the aorta is broad, imaging
      features like contrast enhancement, signal intensity, and metabolic activity may
      help in making the correct diagnosis. Examples of the imaging presentation of
      these rare primary tumors and more common secondary tumors that may affect the
      aorta are presented in this article.

PMID- 22624971
TI  - Cadmium-induced cyto- and genotoxicity are organ-dependent in lettuce.
AB  - Cadmium is a priority pollutant. Its mechanisms and effects within different
      plant organs remain unclear. Here, cyto-genotoxicity biomarkers were evaluated in
      roots and leaves after Cd exposure (0, 1, 10, and 50 MUM) of the model crop
      Lactuca sativa L. (cv. "Reine de Mai"). Overall, superoxide dismutase (SOD) and
      catalase (CAT) activities were stimulated in leaves, where Cd accumulation was
      lower in comparison to that in roots. In roots, SOD and peroxidase (POX, APX)
      activities were stimulated. Moreover, in both organs glutathione reductase (GR)
      was not affected by Cd. Overall, the H(2)O(2) content increased in both organs,
      while the total antioxidant capacity decreased in leaves and increased in roots
      with Cd concentrations. In both organs, lipid and protein oxidation rose with
      consequent increase of membrane permeability. Simultaneously, the comet assay
      showed that tail moment, tail length, and % tail DNA were maximum for 1 MUM. For
      10 MUM, shorter tails were found suggesting induced Cd-DNA adducts that lead to
      DNA-DNA/DNA-protein cross-links, and/or formation of longer DNA fragments, and/or
      impairment of DNA repair mechanisms, while at 50 MUM, nucleoids sensitivity to
      the technique was evident. This result was consistent with the maximum
      micronuclei frequency found for the 10 MUM Cd dose in roots, suggesting that the
      surviving cells in this organ had an increase of mitotic catastrophe and that DNA
      repair systems for blocking cell cycle were dysfunctional. In lower Cd
      concentrations, root cells might have developed strategies to repair damaged DNA
      by blocking the cell cycle at specific checkpoints, thus avoiding mitotic
      catastrophe. Roots at 1 MUM showed a cell cycle blockage trend at the G(2)
      checkpoint, while those at higher concentrations presented S phase delay. We
      finally discuss a general model of Cd-organ interaction covering these cyto- and
      genotoxic effects and the potential use of this cultivar in phytoremediation
      strategies.

PMID- 22624972
TI  - Interval colon cancer in a Lynch syndrome patient under annual colonoscopic
      surveillance: a case for advanced imaging techniques?
AB  - BACKGROUND: Lynch syndrome confers increased risk for various malignancies,
      including colorectal cancer. Colonoscopic surveillance programs have led to
      reduced incidence of colorectal cancer and reduced mortality from colorectal
      cancer. Colonoscopy every 1-2 years beginning at age 20-25, or 10 years earlier
      than the first diagnosis of colorectal cancer in a family, with annual
      colonoscopy after age 40, is the recommended management for mutation carriers.
      Screening programs have reduced colon cancer mortality, but interval cancers may
      occur. CASE PRESENTATION: We describe a 48-year-old woman with Lynch syndrome who
      was found to have an adenoma with invasive colorectal cancer within one year
      after a normal colonoscopy. CONCLUSION: Our patient illustrates two current
      concepts about Lynch syndrome: 1) adenomas are the cancer precursor and 2) such
      adenomas may be "aggressive," in the sense that the adenoma progresses more
      readily and more rapidly to carcinoma in this setting compared to usual
      colorectal adenomas. Our patient's resected tumor invaded only into submucosa and
      all lymph nodes were negative; in that sense, she represents a success for annual
      colonoscopic surveillance. Still, this case does raise the question of whether
      advanced imaging techniques are advisable for surveillance colonoscopy in these
      high-risk patients.

PMID- 22624973
TI  - Submucosal neoplasms of the laryngeal introitus.
AB  - BACKGROUND: The differential diagnosis of endolaryngeal mesenchymal neoplasms
      includes a wide spectrum of benign and malignant pathologies, which have been
      rarely photo-documented and assessed as a group. METHODS: Non-epithelial
      neoplasms of the endolarynx seen at our centre from 2002 to 2011 (n = 38; 36
      treated at our institution) were retrospectively reviewed, with attention to
      clinical presentation, radiographic imaging, operative management, histology, and
      pre- and post-operative endoscopy. Submucosal squamous cell carcinomas, mucosal
      cysts, amyloid and Teflon granulomas were excluded. RESULTS: Twenty-three of a
      total of 36 patients underwent definitive endoscopic surgical treatment.
      Supraglottic pathologies included lymphoma, lipoma, neuroendocrine carcinoma,
      lymphangioma, oncocytoma, haemangioma, synovial cell sarcoma and benign spindle
      cell neoplasm. Transglottic pathologies included synovial cell sarcoma and
      granular cell tumour. Glottic pathologies included granular cell tumour, osteoma,
      rhabdomyoma, rhabdomycosarcoma and myofibroblastic sarcoma. Subglottic
      pathologies included chondrosarcoma, neurofibroma, adenoid cystic carcinoma and
      vascular malformation. CONCLUSION: The site of origin, degree of malignant
      behaviour and sensitivity to adjuvant treatment determined the course of surgical
      management, i.e. endolaryngeal versus transcervical, and limited removal versus
      wider resection.

PMID- 22624975
TI  - Role of encapsulation of Na+ and F- ions on the Diels-Alder reactivity of C32.
AB  - The density functional theory (DFT)-based Becke's three parameter hybrid exchange
      functional and Lee-Yang-Parr correlation functional (B3LYP) calculations have
      been performed to understand the role of encapsulation of Na(+) and F(-) ions on
      the Diels-Alder reactivity of C(32). In this context, C(32) has been taken as the
      dienophile and cis-1,3-butadiene has been considered as diene. Results obtained
      from the calculations on the Na(+)@C(32) and F(-)@C(32) have also been compared
      with that of C(32). It is found from the results that encapsulated Na(+) ion acts
      as a catalyst, whereas the encapsulated F(-) does not accelerate the reaction
      between C(32) and cis-1,3-butadiene. Thus, the reactivity of F(-)@C(32) is less
      than that of free C(32) and Na(+)@C(32). Formation of adduct involving [5,5]-B
      bond is preferred over other bonds. The energy decomposition analysis has been
      applied to understand the role of confinement on an encaged ion. The part played
      by the charge transfer interaction is evident from the NBO analysis. The frontier
      orbital analysis points out that the reaction is driven by the normal electron
      demand.

PMID- 22624974
TI  - The Atlantic-Mediterranean watershed, river basins and glacial history shape the
      genetic structure of Iberian poplars.
AB  - Recent phylogeographic studies have elucidated the effects of Pleistocene
      glaciations and of Pre-Pleistocene events on populations from glacial refuge
      areas. This study investigates those effects in riparian trees (Populus spp.),
      whose particular features may convey enhanced resistance to climate fluctuations.
      We analysed the phylogeographic structure of 44 white (Populus alba), 13 black
      (Populus nigra) and two grey (Populus x canescens) poplar populations in the
      Iberian Peninsula using plastid DNA microsatellites and sequences. We also
      assessed fine-scale spatial genetic structure and the extent of clonality in four
      white and one grey poplar populations using nuclear microsatellites and we
      determined quantitative genetic differentiation (Q(ST) ) for growth traits in
      white poplar. Black poplar displayed higher regional diversity and lower
      differentiation than white poplar, reflecting its higher cold-tolerance. The
      dependence of white poplar on phreatic water was evidenced by strong
      differentiation between the Atlantic and Mediterranean drainage basins and among
      river basins, and by weaker isolation by distance within than among river basins.
      Our results suggest confinement to the lower river courses during glacial periods
      and moderate interglacial gene exchange along coastlines. In northern Iberian
      river basins, white poplar had lower diversity, fewer private haplotypes and
      larger clonal assemblies than in southern basins, indicating a stronger effect of
      glaciations in the north. Despite strong genetic structure and frequent asexual
      propagation in white poplar, some growth traits displayed adaptive divergence
      between drainage and river basins (Q(ST) >F(ST)), highlighting the remarkable
      capacity of riparian tree populations to adapt to regional environmental
      conditions.

PMID- 22624976
TI  - Highly luminescent and nontoxic amine-capped nanoparticles from porous silicon:
      synthesis and their use in biomedical imaging.
AB  - Stable and brightly luminescent amine-terminated Si nanoparticles (SiNPs) have
      been synthesized from electrochemically etched porous silicon (PSi). The surface
      amine termination was confirmed by FTIR, NMR, and XPS studies. The mean diameter
      of the crystal core of 4.6 nm was measured by transmission electron microscopy
      (TEM), which is in a good agreement with the size obtained by dynamic light
      scattering (DLS). The dry, amine-terminated product can be obtained from bulk
      silicon wafers in less than 4 h. This represents a significant improvement over
      similar routines using PSi where times of >10 h are common. The emission quantum
      yield was found to be about 22% and the nanoparticles exhibited an exceptional
      stability over a wide pH range (4-14). They are resistant to aging over several
      weeks. The amine-terminated SiNPs showed no significant cytotoxic effects toward
      HepG2 cells, as assessed with MTT assays. 

PMID- 22624977
TI  - PICK1 expression in reactive astrocytes within the spinal cord of amyotrophic
      lateral sclerosis (ALS) rats.
AB  - AIMS: The protein interacting with C kinase 1 (PICK1), a PDZ domain-containing
      protein mainly expressed in the central nervous system, interacts with the
      glutamate receptor subunit GluR2, with the glutamate transporter GLT-1b and with
      the enzyme serine racemase. These three proteins appear as key actors in the
      glutamate-mediated excitotoxicity associated with amyotrophic lateral sclerosis
      (ALS), in both patients and animal models of the disease. In this study, we
      examined the expression of PICK1 in the spinal cord of transgenic rats expressing
      a mutated form of the human superoxide dismutase 1 (hSOD1(G93A) ) during the
      progression of the disease. METHODS: Expression of PICK1 was examined by real
      time qPCR at presymptomatic and symptomatic stages as well as at end-stage. The
      expression of PICK1 in the different cell types of the spinal cord was examined
      by immunohistochemistry. RESULTS: The overall expression of PICK1 is not modified
      in cervical and lumbar spinal cord of transgenic (hSOD1(G93A) ) rats during the
      progression of the disease. Nonetheless, immunohistochemical studies of lumbar
      ventral horns revealed a shift of PICK1 expression from motor neurones in healthy
      rats to activated astrocytes in end-stage hSOD1(G93A) animals. CONCLUSIONS:
      Considering the documented influence of PICK1 expression on d-serine release and
      glutamate transport in astrocytes, these findings point to a potential
      implication of PICK1 in the progression of ALS.

PMID- 22624978
TI  - Is prevention of atopic eczema with hydrolyzed formulas cost-effective? A health
      economic evaluation from Germany.
AB  - OBJECTIVE: The German Infant Nutritional Intervention (GINI) trial, a
      prospective, randomized, double-blind intervention, enrolled children with a
      hereditary risk for atopy. When fed with certain hydrolyzed formulas for the
      first 4 months of life, the risk was reduced by 26-45% in PP and 8-29% in
      intention-to-treat (ITT) analyses compared with children fed with regular cow's
      milk at age 6. The objective was to assess the cost-effectiveness of feeding
      hydrolyzed formulas. PATIENTS AND METHODS: Cost-effectiveness was assessed with a
      decision tree model programmed in TreeAge. Costs and effects over a 6-yr period
      were analyzed from the perspective of the German statutory health insurance (SHI)
      and a societal perspective at a 3% effective discount rate followed by
      sensitivity analyses. RESULTS: The extensively hydrolyzed casein formula would be
      the most cost-saving strategy with savings of 478 ? per child treated in the ITT
      analysis (CI95%: 12 ?; 852 ?) and 979 ? in the PP analysis (95%CI: 355 ?; 1455 ?)
      from a societal perspective. If prevented cases are considered, the partially
      whey hydrolyzed formula is cost-saving (ITT -5404 ?, PP -6358 ?). From an SHI
      perspective, the partially whey hydrolyzed formula is cost-effective, but may
      also be cost-saving depending on the scenario. An extensively hydrolyzed whey
      formula also included into the analysis was dominated in all analyses.
      CONCLUSIONS: For the prevention of AE, two formulas can be cost-effective or even
      cost-saving. We recommend that SHI should reimburse formula feeding or at least
      the difference between costs for cow's milk formula and the most cost-effective
      formula.

PMID- 22624979
TI  - Chlamydia co-opts the rod shape-determining proteins MreB and Pbp2 for cell
      division.
AB  - Chlamydiae are obligate intracellular bacterial pathogens that have extensively
      reduced their genome in adapting to the intracellular environment. The chlamydial
      genome contains only three annotated cell division genes and lacks ftsZ. How this
      obligate intracellular pathogen divides is uncharacterized. Chlamydiae contain
      two high-molecular-weight (HMW) penicillin binding proteins (Pbp) implicated in
      peptidoglycan synthesis, Pbp2 and Pbp3/FtsI. We show here, using HMW Pbp-specific
      penicillin derivatives, that both Pbp2 and Pbp3 are essential for chlamydial cell
      division. Ultrastructural analyses of antibiotic-treated cultures revealed
      distinct phenotypes: Pbp2 inhibition induced internal cell bodies within a single
      outer membrane whereas Pbp3 inhibition induced elongated phenotypes with little
      internal division. Each HMW Pbp interacts with the Chlamydia cell division
      protein FtsK. Chlamydiae are coccoid yet contain MreB, a rod shape-determining
      protein linked to Pbp2 in bacilli. Using MreB-specific antibiotics, we show that
      MreB is essential for chlamydial growth and division. Importantly, co-treatment
      with MreB-specific and Pbp-specific antibiotics resulted in the MreB-inhibited
      phenotype, placing MreB upstream of Pbp function in chlamydial cell division.
      Finally, we showed that MreB also interacts with FtsK. We propose that, in
      Chlamydia, MreB acts as a central co-ordinator at the division site to substitute
      for the lack of FtsZ in this bacterium.

PMID- 22624980
TI  - miR-34a is downregulated in cis-diamminedichloroplatinum treated sinonasal
      squamous cell carcinoma patients with poor prognosis.
AB  - For the purpose of analyzing mechanisms related to the cis
      diamminedichloroplatinum resistance in head and neck squamous cell carcinoma, we
      analyzed RPMI2650 and its derived previously established cis
      diamminedichloroplatinum resistant cell line RPMI2650CR. To identify resistant
      phenotype-related microRNAs, we compared microRNA expressions between RPMI2650CR
      and RPMI2650 by microarray. One of the microRNAs as downregulated, miR-34a, was
      further investigated. Decreased expression of miR-34a in RPMI2650CR was confirmed
      by quantitative reverse transcription-polymerase chain reaction, but introduction
      of the miR-34a precursor into RPMI2650CR or the inhibitor of miR-34a into
      RPMI2650 did not change cis-diamminedichloroplatinum sensitivities. However, 24
      patients with sinonasal squamous cell carcinomas treated with intra-arterial
      infusion of cis-diamminedichloroplatinum showed a significant association between
      decreased expression of miR-34a and poor disease specific survival (P = 0.0015),
      poor disease free survival (P = 0.0019), and poor local control rates (P = 0.017)
      (median follow-up period: 53 months). Furthermore, multivariate analyses
      demonstrated significant associations between miR-34a expression and the hazard
      ratios of disease free survival at 0.005 (95% confidence interval [CI] 0.00-0.29,
      P = 0.011) and local control rate at 0.008 (95% CI 0.00-0.44, P = 0.019),
      although other parameters such as age, gender, treatment method, T and N stages
      did not show any similar association. These results strongly suggest that miR-34a
      expression can be an independent prognostic biomarker in patients with sinonasal
      squamous cell carcinoma who are undergoing treatment with cis
      diamminedichloroplatinum.

PMID- 22624981
TI  - Simple and highly enantioselective electrochemical aptamer-based binding assay
      for trace detection of chiral compounds.
AB  - A new electrochemical methodology is reported for monitoring in homogeneous
      solution the enantiospecific binding of a small chiral analyte to an aptamer. The
      principle relies on the difference of diffusion rates between the targeted
      molecule and the aptamer/target complex, and thus on the ability to more easily
      electrochemically detect the former over the latter in a homogeneous solution.
      This electrochemical detection strategy is significant because, in contrast to
      the common laborious and time-consuming heterogeneous binding approaches, it is
      based on a simple and fast homogeneous binding assay which does not call for an
      aptamer conformational change upon ligand binding. The methodology is here
      exemplified with the specific chiral recognition of trace amounts of l- or d
      tyrosinamide by a 49-mer d- or l-deoxyribooligonucleotide receptor. Detection as
      low as 0.1% of the minor enantiomer in a nonracemic mixture can be achieved in a
      very short analysis time (<1 min). The assay finally combines numerous attractive
      features including simplicity, rapidity, low cost, flexibility, low volume
      samples (few microliters), and homogeneous format.

PMID- 22624983
TI  - Fatty acid composition in the mature milk of Bolivian forager-horticulturalists:
      controlled comparisons with a US sample.
AB  - Breast milk fatty acid (FA) composition varies greatly among individual women,
      including in percentages of the long-chain polyunsaturated FAs (LCPUFA) 20:4n-6
      (arachidonic acid, AA) and 22:6n-3 (docosahexaenoic acid, DHA), which are
      important for infant neurological development. It has been suggested that owing
      to wide variation in milk LCPUFA and low DHA in Western diets, standards of milk
      FA composition should be derived from populations consuming traditional diets. We
      collected breast milk samples from Tsimane women at varying lactational stages (6
      82 weeks). The Tsimane are an indigenous, natural fertility, subsistence-level
      population living in Amazonia Bolivia. Tsimane samples were matched by
      lactational stage to samples from a US milk bank, and analysed concurrently for
      FA composition by gas-liquid chromatography. We compared milk FA composition
      between Tsimane (n = 35) and US (n = 35) mothers, focusing on differences in
      LCPUFA percentages that may be due to population-typical dietary patterns. Per
      total FAs, the percentages of AA, DHA, total n-3 and total n-6 LCPUFA were
      significantly higher among Tsimane mothers. Mean percentages of 18:2n-6 (linoleic
      acid) and trans FAs were significantly higher among US mothers. Tsimane mothers'
      higher milk n-3 and n-6 LCPUFA percentages may be due to their regular
      consumption of wild game and freshwater fish, as well as comparatively lower
      intakes of processed foods and oils that may interfere with LCPUFA synthesis.

PMID- 22624984
TI  - Validation of a new tool to assess health-related quality of life in psoriasis:
      the PSO-LIFE questionnaire.
AB  - BACKGROUND: Several questionnaires have been used to measure health related
      quality of life (HRQoL) in patients with psoriasis, few have been adapted for use
      in Spain; none of them was developed specifically for the Spanish population. The
      purpose of the study was to validate and assess the sensitivity to change of a
      new questionnaire to measure HRQOL in patients with psoriasis (PSO-LIFE).
      METHODS: Observational, prospective, multicenter study performed in centers
      around Spain. Patients with active or inactive psoriasis completed the PSO-LIFE
      together with other Dermatology Quality of Life Index (DLQI) and Psoriasis
      Disability Index (PDI). A control group of patients with urticaria or atopic
      dermatitis was also included. Internal consistency and test-retest reliability of
      the PSO-LIFE were assessed by calculating Cronbach's alpha and Intraclass
      Correlation Coefficient (ICC). Validity was assessed by examining factorial
      structure, the capacity to discriminate between groups, and correlations with
      other measures. Sensitivity to change was measured using effect sizes. RESULTS:
      The final sample included for analysis consisted of 304 patients and 56 controls.
      Mean (SD) age of psoriasis patients was 45.3 (14.5) years compared to 38.8 (14)
      years for controls (p < 0.01). Cronbach's alpha for the PSO-LIFE was 0.95 and
      test-retest reliability using the ICC was 0.98. Factor analysis showed the
      questionnaire to be unidimensional. Mean (SD) PSO-LIFE scores differed between
      patients with psoriasis and controls (64.9 [22.5] vs 69.4 [17.3]; p < 0.05),
      between those with active and inactive disease (57.4 [20.4] vs 76.4 [20.6]; p <
      0.01), and between those with visible and non-visible lesions (63.0 [21.9] vs.
      74.8 [23.9]; p < 0.01). The correlation between PSO-LIFE and PASI scores was
      moderate (r = -0.43) while correlations with DLQI and PDI dimensions ranged from
      moderate to high (between 0.4 and 0.8). Effect size on the PSO-LIFE in patients
      reporting 'much improved' health status at study completion was 1.01 (large
      effect size). CONCLUSIONS: The present results provide substantial support for
      the reliability, validity, and responsiveness of the PSO-LIFE questionnaire in
      the population for which it was designed.

PMID- 22624985
TI  - Heroin inhalation-induced unilateral complete hippocampal stroke.
AB  - A 33-year-old man presented to our clinic with amnesia 48 hours after his first
      heroin inhalation. Examination showed lateral tongue biting and anterograde
      amnesia demonstrated by impaired performance on verbal and visual Wechsler Memory
      Scale-Revised tests carried out 10 days after onset, suggesting hippocampal
      involvement. Magnetic resonance imaging (MRI) of the brain was performed 48 hours
      after heroin snorting and evoked cortical laminar necrosis (CLN) of the left
      hippocampus without vascular abnormality. This is the first description of
      complete hippocampal CLN as a complication subsequent to acute intranasal heroine
      abuse. While the pathogenic mechanism remains uncertain, our case provides a very
      specific MRI lesion pattern and highlights the risk of intranasal heroin uptake
      induced neurological complication. 

PMID- 22624986
TI  - 3D nitrogen-doped graphene aerogel-supported Fe3O4 nanoparticles as efficient
      electrocatalysts for the oxygen reduction reaction.
AB  - Three-dimensional (3D) N-doped graphene aerogel (N-GA)-supported Fe(3)O(4)
      nanoparticles (Fe(3)O(4)/N-GAs) as efficient cathode catalysts for the oxygen
      reduction reaction (ORR) are reported. The graphene hybrids exhibit an
      interconnected macroporous framework of graphene sheets with uniform dispersion
      of Fe(3)O(4) nanoparticles (NPs). In studying the effects of the carbon support
      on the Fe(3)O(4) NPs for the ORR, we found that Fe(3)O(4)/N-GAs show a more
      positive onset potential, higher cathodic density, lower H(2)O(2) yield, and
      higher electron transfer number for the ORR in alkaline media than Fe(3)O(4) NPs
      supported on N-doped carbon black or N-doped graphene sheets, highlighting the
      importance of the 3D macropores and high specific surface area of the GA support
      for improving the ORR performance. Furthermore, Fe(3)O(4)/N-GAs show better
      durability than the commercial Pt/C catalyst.

PMID- 22624987
TI  - Family history differs between young women with myocardial infarction and
      ischemic stroke: results from the RATIO case-control study.
AB  - BACKGROUND: Family history may help in risk stratification, especially in the
      young. This study assesses the predictive value of a positive family history of
      cardiovascular disease for myocardial infarction (MI) and ischemic stroke (IS).
      METHODS/RESULTS: The RATIO study case-control study includes women with MI (N =
      248), IS (N = 203) and 925 healthy matched controls. Odds ratios (ORs) and 95%
      confidence intervals (95%CI) were calculated with logistic regression. The risk
      of MI was almost fourfold increased in women with a family history positive for
      MI (OR 3.70, 95%CI 2.68-5.10), whereas the risk of IS was, if anything, only
      slightly elevated (1.25, 0.83-1.87). A family history of stroke (ischemic and
      hemorrhagic) was associated with a twofold increase in MI risk (2.00, 1.29-3.12),
      whereas the IS risk was again not clearly associated (1.37, 0.79-2.40).
      CONCLUSIONS: The predictive value of a family history for cardiovascular disease
      differs between MI and IS.

PMID- 22624988
TI  - Beta-blockers use and risk of hyperglycemia in acute stroke patients.
AB  - BACKGROUND: Beta-adrenergic blockade prevents or diminishes stress-induced
      hyperglycemia in different experimental models. The aim of the study was to
      determine if the use of beta-blockers before stroke reduces the risk of acute
      hyperglycemia in stroke patients. METHODS: We analyzed the data of 603
      consecutive patients with acute ischemic stroke and without pre-stroke diagnosis
      of diabetes mellitus admitted to stroke unit within 24 h after symptoms onset.
      RESULTS: Plasma glucose level on admission (6.0 +/- 1.4 vs 6.6 +/- 1.9 mmol/L, P
      = 0.01) and fasting glucose on day 1 (5.2 +/- 1.1 vs 5.7 +/- 1.1 mmol/L, P =
      0.02) were significantly lower in patients treated with beta-blockers before
      stroke than in those who did not receive such a treatment. On multivariate
      logistic analysis beta-blockers use before stroke was associated with reduced
      risk of glucose level on admission >=7.8 mmol/L (OR: 0.22, 95%CI: 0.07-0.74) and
      fasting glucose on day 1 >= 7.0 mmol/L (OR: 0.21, 95%CI: 0.05-0.91). The risk of
      fasting hyperglycemia defined as glucose >=6.1 mmol/L did not differ between
      groups. CONCLUSIONS: Beta-blockage before stroke onset may result in lower plasma
      glucose on admission and prevent early hyperglycemia in patients without pre
      stroke diagnosis of diabetes mellitus.

PMID- 22624989
TI  - Effect of age, gender and cardiovascular risk factors on carotid distensibility
      during 6-year follow-up. The cardiovascular risk in Young Finns study.
AB  - OBJECTIVE: Arterial elasticity decreases with aging. We evaluated the role of
      conventional cardiovascular risk factors in this process and studied the
      modifying effect of gender in a population of young adults. METHODS: 6-year
      follow-up study that included 1711 subjects (aged 32 +/- 5 years) who had carotid
      artery distensibility (Cdist) measured at baseline (in 2001) and at follow-up (in
      2007). Risk factors measurements included waist circumference, body mass index,
      lipids, glucose, C-reactive protein, smoking and family history of coronary
      disease. RESULTS: In a multivariable model, baseline age (beta +/- SEM = -0.024
      +/- 0.003, P < 0.001), waist circumference (beta +/- SEM = -0.005 +/- 0.002, P =
      0.009) and insulin (beta +/- SEM = -0.097 +/- 0.034, P = 0.005) were associated
      with 6-year change in Cdist. The 6-year increase in waist circumference (beta +/-
      SEM = -0.016 +/- 0.003, P < 0.001) and systolic blood pressure (beta +/- SEM = 
      0.005 +/- 0.002, P = 0.006) were associated with reduced Cdist. In women, an
      increase in glucose was associated with reduced Cdist (beta +/- SEM = -0.074 +/-
      0.025, P = 0.004). Decreasing trend in Cdist levels was observed with increasing
      number of metabolic syndrome risk factors in women (P = 0.0001) but not in men (P
      = 0.18) (P for interaction 0.02). CONCLUSIONS: In addition to age, increased
      adiposity and insulin levels were strong predictors for impaired arterial
      elasticity. Moreover, our results suggest that arterial function in women may be
      more vulnerable to the atherogenic effects of hyperglycemia and increased risk
      factor burden compared to men in young adulthood.

PMID- 22624990
TI  - Zotarolimus-eluting vs. sirolimus-eluting coronary stents in patients with and
      without acute coronary syndromes: a SORT OUT III substudy.
AB  - OBJECTIVES: To compare clinical outcomes among patients with acute coronary
      syndrome treated with zotarolimus-eluting and sirolimus-eluting stents in the
      SORT OUT III trial. BACKGROUND: Currently, only limited data allow direct
      comparison of clinical outcomes among patients with acute coronary syndrome
      treated with a second-generation drug-eluting stent (DES) eluting zotarolimus vs.
      a first-generation DES eluting sirolimus. METHODS: Patients with acute coronary
      syndrome (n=1052) were randomized to treatment with zotarolimus-eluting (n=506)
      or sirolimus-eluting (n=546) stents and followed for 18 months. The primary
      composite endpoint, major adverse cardiac events (MACE), was defined as a
      composite of cardiac death, myocardial infarction or target vessel
      revascularization. RESULTS: Zotarolimus-eluting stent treatment compared to
      sirolimus-eluting stent treatment was associated with increased rates of MACE
      (8.7% vs. 5.0%; hazard ratio (HR), 1.78; 95% confidence interval (CI), 1.10-2.88;
      P=0.02) and TVR (6.8% vs. 3.9%; HR, 1.77; 95% CI, 1.03-3.04; P=0.04), while all
      cause death, cardiac death, myocardial infarction and definite stent thrombosis
      did not differ significantly. In the same trial, stable angina pectoris patients
      (n=1206) were randomized to zotarolimus-eluting (n=614) and sirolimus-eluting
      (n=592) stents with similar results. CONCLUSIONS: With and without acute coronary
      syndromes, patients treated with the sirolimus-eluting stent had better clinical
      outcomes than those treated with the zotarolimus-eluting stent.

PMID- 22624991
TI  - Activity-screening-guided isolation and purification for vasodilative effects
      compounds from Radix Astragali by high-speed counter-current chromatography using
      gradient elution.
AB  - The animal models were conducted to activity screening of different ethanol
      fraction from Radix Astragali. Eluted from the macroporous adsorptive resins, the
      potential active fraction that had vasodilative effects was isolated and purified
      by high-speed counter-current chromatography (HSCCC) using gradient elution. The
      solvent system was composed of chloroform-methanol-acetic acid-water (2 : 1 : 1 :
      1, v/v/v/v). The flow rate was 1.0 mL min(-1) initially and changed to 2.0 mL
      min(-1) at 300 min. Four flavonoids named calycosin-7-O-beta- D -glycoside (a),
      formononetin-7-O-beta- D -glycoside (b), calycosin (c) and formononetin (d) with
      purity over 94% were obtained and then identified by (1)H NMR and (13)C NMR.

PMID- 22624992
TI  - Bovine serum albumin further enhances the effects of organic solvents on
      increased yield of polymerase chain reaction of GC-rich templates.
AB  - BACKGROUND: While being a standard powerful molecular biology technique,
      applications of the PCR to the amplification of high GC-rich DNA samples still
      present challenges which include limited yield and poor specificity of the
      reaction. Organic solvents, including DMSO and formamide, have been often
      employed as additives to increase the efficiency of amplification of high GC
      content (GC > 60%) DNA sequences. Bovine serum albumin (BSA) has been used as an
      additive in several applications, including restriction enzyme digestions as well
      as in PCR amplification of templates from environmental samples that contain
      potential inhibitors such as phenolic compounds. FINDINGS: Significant increase
      in PCR amplification yields of GC-rich DNA targets ranging in sizes from 0.4 kb
      to 7.1 kb were achieved by using BSA as a co-additive along with DMSO and
      formamide. Notably, enhancing effects of BSA occurs in the initial PCR cycles
      with BSA additions having no detrimental impact on PCR yield or specificity. When
      a PCR was set up such that the cycling parameters paused after every ten cycles
      to allow for supplementation of BSA, combining BSA and organic solvent produced
      significantly higher yields relative to conditions using the solvent alone. The
      co-enhancing effects of BSA in presence of organic solvents were also obtained in
      other PCR applications, including site-directed mutagenesis and overlap extension
      PCR. CONCLUSIONS: BSA significantly enhances PCR amplification yield when used in
      combination with organic solvents, DMSO or formamide. BSA enhancing effects were
      obtained in several PCR applications, with DNA templates of high GC content and
      spanning a broad size range. When added to the reaction buffer, promoting effects
      of BSA were seen in the first cycles of the PCR, regardless of the size of the
      DNA to amplify. The strategy outlined here provides a cost-effective alternative
      for increasing the efficiency of PCR amplification of GC-rich DNA targets over a
      broad size range.

PMID- 22624993
TI  - Topical antioxidants protect the skin from chemical-induced irritation in the
      repetitive washing test: a placebo-controlled, double-blind study.
AB  - BACKGROUND: There is increasing evidence that reactive oxygen species play an
      important role in the development of both irritant and allergic contact
      dermatitis. OBJECTIVES: To assess the potential of topical antioxidants to
      prevent the development of experimentally induced irritant contact dermatitis.
      METHODS: We evaluated the effect of a cream containing a combination of
      antioxidants on sodium lauryl sulfate-induced irritant contact dermatitis in the
      repetitive washing test. As readout parameters for skin barrier function and
      cutaneous inflammation stratum corneum hydration, cutaneous blood flow and
      transepidermal water loss were assessed in 25 volunteers with bioengineering
      methods. RESULTS: In comparison with the cream base and a frequently used barrier
      cream, the antioxidant cream had high radical scavenging activity and effectively
      protected the skin from chemical-induced irritation. CONCLUSIONS: The superiority
      of the cream with antioxidants to the cream base suggests that reactive oxygen
      species, at least in part, play a role in the development of irritant contact
      dermatitis.

PMID- 22624994
TI  - The relationship between urban environment and the inflammatory bowel diseases: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The objective of this study was to conduct a systematic review with
      meta-analysis of studies assessing the association between living in an urban
      environment and the development of the Crohn's disease (CD) or ulcerative colitis
      (UC). METHODS: A systematic literature search of MEDLINE (1950-Oct. 2009) and
      EMBASE (1980-Oct. 2009) was conducted to identify studies investigating the
      relationship between urban environment and IBD. Cohort and case-control studies
      were analyzed using incidence rate ratio (IRR) or odds ratio (OR) with 95 %
      confidence intervals (CIs), respectively. Stratified and sensitivity analyses
      were performed to explore heterogeneity between studies and assess effects of
      study quality. RESULTS: The search strategy retrieved 6940 unique citations and
      40 studies were selected for inclusion. Of these, 25 investigated the
      relationship between urban environment and UC and 30 investigated this
      relationship with CD. Included in our analysis were 7 case-control UC studies, 9
      case-control CD studies, 18 cohort UC studies and 21 cohort CD studies. Based on
      a random effects model, the pooled IRRs for urban compared to rural environment
      for UC and CD studies were 1.17 (1.03, 1.32) and 1.42 (1.26, 1.60), respectively.
      These associations persisted across multiple stratified and sensitivity analyses
      exploring clinical and study quality factors. Heterogeneity was observed in the
      cohort studies for both UC and CD, whereas statistically significant
      heterogeneity was not observed for the case-control studies. CONCLUSIONS: A
      positive association between urban environment and both CD and UC was found.
      Heterogeneity may be explained by differences in study design and quality
      factors.

PMID- 22625175
TI  - Control of glutamate homeostasis in Bacillus subtilis: a complex interplay
      between ammonium assimilation, glutamate biosynthesis and degradation.
AB  - Glutamate, the major amino group donor in anabolism, is synthesized by the
      combined action of the glutamine synthetase (GS) and the glutamate synthase
      (GOGAT) in Bacillus subtilis. The glutamate dehydrogenase (GDH) exclusively
      degrades glutamate. GS and GDH are both trigger enzymes, active in nitrogen
      metabolism and in controlling gene expression. Feedback-inhibited GS (FBI-GS)
      controls DNA-binding activities of two transcription factors, the repressor GlnR
      and TnrA, the global regulator of nitrogen metabolism. FBI-GS binds to and
      activates GlnR. This protein complex inhibits GS formation and thus glutamine
      synthesis. Moreover, FBI-GS inhibits DNA-binding activity of TnrA. Glutamate
      biosynthesis, the reaction linking carbon with nitrogen metabolism, is controlled
      by GDH. Together with glutamate GDH inhibits GltC, the transcription factor that
      activates expression of the GOGAT genes. Thus, GS and GDH control glutamine and
      glutamate synthesis, respectively, depending on the nitrogen status of the cell.
      B. subtilis lacking a functional GDH show a severe growth defect. Interestingly,
      the growth defect is suppressed by the rapid activation of an inactive GDH. Thus,
      maintenance of glutamate homeostasis is crucial for cellular vitality. This
      review covers the recent work on the complex control of glutamine and glutamate
      metabolism in the Gram-positive model organism B. subtilis.

PMID- 22625176
TI  - Leptospirosis following a major flood in Central Queensland, Australia.
AB  - Throughout December 2010 and January 2011, Queensland experienced widespread
      flooding due to unusually protracted and heavy rainfalls. In mid-January 2011,
      four individuals from a small community in Central Queensland were hospitalized
      with leptospirosis. A further five cases were subsequently identified from around
      Central Queensland, bringing the total to nine. Microscopic agglutination testing
      found that serovar Arborea (Leptospira borgpetersenii serovar Arborea) was
      presumptively responsible for leptospirosis in seven of nine confirmed cases.
      Serovars Hardjo and Australis were identified in samples from two remaining
      cases. All cases had exposure to flood water. No single exposure source was
      identified. This is the first reported outbreak of leptospirosis in Central
      Queensland and the first report of leptospirosis cases associated with flood
      water inundation in Queensland. Public health authorities should continue to
      promote awareness of leptospirosis in flood-affected populations. Healthcare
      providers must maintain a high level of suspicion for leptospirosis during and
      after flood events.

PMID- 22625177
TI  - Crossing the divide: gene flow produces intergeneric hybrid in feral transgenic
      creeping bentgrass population.
AB  - Gene flow is the most frequently expressed public concern related to the
      deregulation of transgenic events (Snow 2002; Ellstrand 2003). However, assessing
      the potential for transgene escape is complex because it depends on the
      opportunities for unintended gene flow, and establishment and persistence of the
      transgene in the environment (Warwick et al. 2008). Creeping bentgrass (Agrostis
      stolonifera L.), a turfgrass species widely used on golf courses, has been
      genetically engineered to be resistant to glyphosate, a nonselective herbicide.
      Outcrossing species, such as creeping bentgrass (CB), which have several
      compatible species, have greater chances for gene escape and spontaneous
      hybridization (i.e. natural, unassisted sexual reproduction between taxa in the
      field), which challenges transgene containment. Several authors have emphasized
      the need for evidence of spontaneous hybridization to infer the potential for
      gene flow (Armstrong et al. 2005). Here we report that a transgenic intergeneric
      hybrid has been produced as result of spontaneous hybridization of a feral
      regulated transgenic pollen receptor (CB) and a nontransgenic pollen donor
      (rabbitfoot grass, RF, Polypogon monspeliensis (L.) Desf.). We identified an off
      type transgenic seedling and confirmed it to be CB * RF intergeneric hybrid. This
      first report of a transgenic intergeneric hybrid produced in situ with a
      regulated transgenic event demonstrates the importance of considering all
      possible avenues for transgene spread at the landscape level before planting a
      regulated transgenic crop in the field. Spontaneous hybridization adds a level of
      complexity to transgene monitoring, containment, mitigation and remediation
      programmes.

PMID- 22625179
TI  - Hydroxyapatite formation on sol-gel derived poly(epsilon-caprolactone)/bioactive
      glass hybrid biomaterials.
AB  - Investigation of novel biomaterials for bone regeneration is based on the
      development of scaffolds that exhibit bone-bonding ability, biocompatibility, and
      sufficient mechanical strength. In this study, using novel poly (epsilon
      caprolactone)/bioactive glass (PCL/BG) hybrids with different organic/inorganic
      ratios, the effects of BG contents on the in vitro bone-like hydroxyapatite (HA)
      formation, mechanical properties, and biocompatibility were investigated. Rapid
      precipitation of HA on the PCL/BG hybrid surfaces were observed after incubating
      in simulated body fluid (SBF) for only 6 h, as confirmed by scanning electron
      microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), Fourier-transform
      infrared spectroscopy (FTIR), and inductively coupled plasma atomic emission
      spectroscopy (ICPS). The ICPS elemental analysis results were further analyzed in
      terms of the Ca(2+) and PO4(3-) which were consumed to form the apatite layer.
      The results revealed that the rate and total amount of HA deposition decreased
      with an increase in PCL content. The compressive modulus and strength of the
      PCL/BG hybrids increased with the decrease in PCL content. The highest values
      were achieved at the lowest PCL content (10 wt %) and were around, 90 MPa and 1.4
      GPa, respectively. To evaluate the cytotoxicity of PCL/BG bioactive hybrids,
      MC3T3-E1 osteoblast-like cells were cultured for up to 72 h. Our data indicated
      that whereas initial cell attachment was marginally lower than the control tissue
      culture poly styrene (TCPS) surface, the hybrid materials promoted cell growth in
      a time-dependent manner. Cell viability within the different PCL/BG hybrid
      samples appeared to be influenced by compositional differences whereby higher PCL
      contents correlated with slight reduction in cell viability. Taken together, this
      study adds important new information to our knowledge on hydroxyapatite
      formation, mechanical properties, and cytotoxic effects of PCL/BG hybrids
      prepared by the sol-gel process using a tertiary glass composition and may have
      considerable potential for bone tissue regeneration applications. 

PMID- 22625178
TI  - Digital switching of local arginine density in a genetically encoded self
      assembled polypeptide nanoparticle controls cellular uptake.
AB  - Cell-penetrating peptides (CPPs) are a class of molecules that enable efficient
      internalization of a wide variety of cargo in diverse cell types, making them
      desirable for delivery of anticancer drugs to solid tumors. For CPPs to be
      useful, it is important to be able to turn their function on in response to an
      external trigger that can be spatially localized in vivo. Here we describe an
      approach to turning on CPP function by modulation of the local density of
      arginine (Arg) residues by temperature-triggered micelle assembly of diblock
      copolymer elastin-like polypeptides (ELP(BC)s). A greater than 8-fold increase in
      cellular uptake occurs when Arg residues are presented on the corona of ELP(BC)
      micelles, as compared to the same ELP(BC) at a temperature in which it is a
      soluble unimer. This approach is the first to demonstrate digital 'off-on'
      control of CPP activity by an extrinsic thermal trigger in a clinically relevant
      temperature range by modulation of the interfacial density of Arg residues on the
      exterior of a nanoparticle.

PMID- 22625180
TI  - Radical quantum yields from formaldehyde photolysis in the 30,400-32,890 cm(-1)
      (304-329 nm) spectral region: detection of radical photoproducts using pulsed
      laser photolysis-pulsed laser induced fluorescence.
AB  - The relative quantum yield for the production of radical products, H + HCO, from
      the UV photolysis of formaldehyde (HCHO) has been measured using a pulsed laser
      photolysis-pulsed laser induced fluorescence (PLP-PLIF) technique across the
      30,400-32,890 cm(-1) (304-329 nm) spectral region of the A(1)A2-X(1)A1 electronic
      transition. The photolysis laser had a bandwidth of 0.09 cm(-1), which is
      slightly broader than the Doppler width of a rotational line of formaldehyde at
      300 K (0.07 cm(-1)), and the yield spectrum shows detailed rotational structure.
      The H and HCO photofragments were monitored using LIF of the OH radical as a
      spectroscopic marker. The OH radicals were produced by rapid reaction of the H
      and HCO photofragments with NO2. This technique produced an "action" spectrum
      that at any photolysis wavelength is the product of the H + HCO radical quantum
      yield and HCHO absorption cross section at the photolysis wavelength and is a
      relative measurement. Using the HCHO absorption cross section previously obtained
      in this laboratory, the relative quantum yield was determined two different ways.
      One produced band specific yields, and the other produced yields averaged over
      each 100 cm(-1). Yields were normalized to a value of 0.69 at 31,750 cm(-1) based
      on the current recommendation of Sander et al. (Sander, S. P.; Abbatt, J.;
      Barker, J. R.; Burkholder, J. B.; Friedl, R. R.; Golden, D. M.; Huie, R. E.;
      Kolb, C. E.; Kurylo, M. J.; Moortgat, G. K.; et al. Chemical Kinetics and
      Photochemical Data for Use in Atmospheric Studies, Evaluation No. 17; Jet
      Propulsion Laboratory: Pasadena, CA, USA, 2011). The resulting radical quantum
      yields agree well with previous experimental studies and the current JPL
      recommendation but show greater wavelength dependent structure. A significant
      decrease in the quantum yield was observed for the 5(0)(1) + 1(0)(1)4(0)(1)
      combination band centered at 31,125 cm(-1). This band has a low absorption cross
      section and has little impact on the calculated atmospheric photodissociation
      rate but is a further indication of the complexity of HCHO photodissociation
      dynamics.

PMID- 22625181
TI  - A single-molecule view of conformational switching of DNA tethered to a gold
      electrode.
AB  - Surfaces that can actively regulate binding affinities or catalytic properties in
      response to external stimuli are a powerful means to probe and control the
      dynamic interactions between the cell and its microenvironment. Active surfaces
      also enable novel functionalities in biosensors and biomolecular separation
      technologies. Although electrical stimuli are often appealing due to their speed
      and localization, the operation of these electrically activated surfaces has
      mostly been characterized with techniques averaging over many molecules. Without
      a molecular-scale understanding of how biomolecules respond to electric fields,
      achieving the ultimate detection sensitivity or localized biological perturbation
      with the ultimate resolution would be difficult. Using electrochemical atomic
      force microscopy, we are able to follow the conformational changes of individual,
      short DNA molecules tethered to a gold electrode in response to an applied
      potential. Our study reveals conformations and dynamics that are difficult to
      infer from ensemble measurements: defects in the self-assembled monolayer (SAM)
      significantly perturb conformations and adsorption/desorption kinetics of surface
      tethered DNA; on the other hand, the SAM may be actively molded by the DNA at
      different potentials. These results underscore the importance of characterizing
      the systems at the relevant length scale in the development of electrically
      switchable biofunctional surfaces.

PMID- 22625182
TI  - Cluster-randomized trial on complementary and responsive feeding education to
      caregivers found improved dietary intake, growth and development among rural
      Indian toddlers.
AB  - Inadequate feeding and care may contribute to high rates of stunting and
      underweight among children in rural families in India. This cluster-randomized
      trial tested the hypothesis that teaching caregivers appropriate complementary
      feeding and strategies for how to feed and play responsively through home-visits
      would increase children's dietary intake, growth and development compared with
      home-visit-complementary feeding education alone or routine care. Sixty villages
      in Andhra Pradesh were randomized into three groups of 20 villages with 200
      mother-infant dyads in each group. The control group (CG) received routine
      Integrated Child Development Services (ICDS); the complementary feeding group
      (CFG) received the ICDS plus the World Health Organization recommendations on
      breastfeeding and complementary foods; and the responsive complementary feeding
      and play group (RCF&PG) received the same intervention as the CFG plus skills for
      responsive feeding and psychosocial stimulation. Both intervention groups
      received bi-weekly visits by trained village women. The groups did not differ at
      3 months on socioeconomic status, maternal and child nutritional indices, and
      maternal depression. After controlling for potential confounding factors using
      the mixed models approach, the 12-month intervention to the CFG and RCF&PG
      significantly (P < 0.05) increased median intakes of energy, protein, Vitamin A,
      calcium (CFG), iron and zinc, reduced stunting [0.19, confidence interval (CI):
      0.0-0.4] in the CFG (but not RCF&PG) and increased (P < 0.01) Bayley Mental
      Development scores (mean = 3.1, CI: 0.8-5.3) in the RCF&PG (but not CFG) compared
      with CG. Community-based educational interventions can improve dietary intake,
      length (CFG) and mental development (RCF&PG) for children under 2 years in food
      secure rural Indian families.

PMID- 22625183
TI  - Distribution of calcium in the ascending aorta in patients undergoing
      transcatheter aortic valve implantation and its relevance to the transaortic
      approach.
AB  - OBJECTIVES: This study sought to identify how many patients suitable for
      transcatheter aortic valve implantation (TAVI) would have a contraindication for
      the transaortic (TAo) approach due to ascending aortic calcification. BACKGROUND:
      TAo is an emerging approach for implantation of the Sapien valve through the
      ascending aorta. A "porcelain aorta" is often considered a contraindication for
      the TAo approach. This may not always be true, as the TAo procedure requires a
      small calcium-free area for the purse-string suture, usually in the upper outer
      quadrant of the distal ascending aorta, identified as the "TAo zone." METHODS: A
      total of 237 patients underwent TAVI between February 2008 and June 2011.
      Multislice computed tomography scans (MSCT) were analyzed for distribution of
      calcium with special attention to the TAo zone. Each MSCT was interrogated in
      cross section and three dimensional (3D) reconstructions. Correlation between the
      calcium distribution on MSCT and the 3D reconstruction with the clinical findings
      was sought in patients undergoing the TAo procedure. RESULTS: The vast majority
      of patients had calcification in the aortic arch (n = 154, 64.9%) and aortic root
      (n = 220, 92.8%). Of the 237 patients, only 1 patient had diffuse calcification
      in the ascending aorta, including the TAo zone, thus precluding a TAo procedure.
      MSCT and 3D reconstruction data in the 33 patients who underwent a TAo procedure,
      including 6 who were identified as having porcelain aorta preoperatively,
      correlated very well with the absence of calcium in the TAo zone during surgery.
      There were no post-procedure neurological events in this group. CONCLUSIONS:
      Conventionally defined porcelain aorta should not be considered a
      contraindication for performing TAVI by the TAo approach.

PMID- 22625184
TI  - Direct percutaneous access technique for transaxillary transcatheter aortic valve
      implantation: "the Hamburg Sankt Georg approach".
AB  - OBJECTIVES: This study questioned whether transaxillary transcatheter aortic
      valve implantation (TAVI) is feasible as a true percutaneous approach using
      percutaneous closure devices. BACKGROUND: Transaxillary TAVI is gaining
      increasing acceptance as an alternative to the transfemoral route; however, the
      access has always been done via surgical cutdown so far. METHODS: Between August
      2010 and September 2011, a total of 24 high-risk patients with severe aortic
      valvular stenosis underwent a percutaneous TAVI procedure by direct puncture of
      the axillary artery without surgical cutdown. For safety reasons and as a target
      for the puncture, a wire was advanced via the ipsilateral brachial artery.
      Moreover, a balloon was placed into the subclavian artery via the femoral artery
      for temporary vessel blockade before percutaneous vessel closure. Vascular
      closure was performed using either the ProStar XL system (Abbott Vascular
      Devices, Redwood City, California) or 2 ProGlide systems (Abbott Vascular
      Devices). RESULTS: The true percutaneous approach was successfully completed in
      all patients (14 left and 8 right axillary artery cases). Overall mortality at 30
      days was 8.3%. Acute vascular closure device success was achieved in 17 patients
      (71%). Vascular closure device success rate was 100% for the ProGlide device and
      37% for the ProStar device, respectively. Seven patients (29%) with failing
      closure devices were treated by endovascular stent graft implantation without the
      need for surgical repair. For the last 12 treated patients, direct closure was
      achieved in 11 patients. CONCLUSIONS: Direct puncture of the axillary artery for
      TAVI is feasible and safe if a wire is placed into the subclavian artery via the
      ipsilateral brachial artery.

PMID- 22625185
TI  - Access for transcatheter aortic valve replacement: which is the preferred route?

PMID- 22625186
TI  - Evaluation of multidimensional geriatric assessment as a predictor of mortality
      and cardiovascular events after transcatheter aortic valve implantation.
AB  - OBJECTIVES: This study evaluated Multidimensional Geriatric Assessment (MGA) as
      predictor of mortality and major adverse cardiovascular and cerebral events
      (MACCE) after transcatheter aortic valve implantation (TAVI). BACKGROUND:
      Currently used global risk scores do not reliably estimate mortality and MACCE in
      these patients. METHODS: This prospective cohort comprised 100 consecutive
      patients >= 70 years undergoing TAVI. Global risk scores (Society of Thoracic
      Surgeons [STS] score, EuroSCORE) and MGA-based scores (cognition, nutrition,
      mobility, activities of daily living [ADL], and frailty index) were evaluated as
      predictors of all-cause mortality and MACCE 30 days and 1 year after TAVI in
      regression models. RESULTS: In univariable analyses, all predictors were
      significantly associated with mortality and MACCE at 30 days and 1 year, except
      for the EuroSCORE at 30 days and instrumental ADL at 30 days and 1 year.
      Associations of cognitive impairment (odds ratio [OR]: 2.98, 95% confidence
      interval [CI]: 1.07 to 8.31), malnutrition (OR: 6.72, 95% CI: 2.04 to 22.17),
      mobility impairment (OR: 6.65, 95% CI: 2.15 to 20.52), limitations in basic ADL
      (OR: 3.63, 95% CI: 1.29 to 10.23), and frailty index (OR: 3.68, 95% CI: 1.21 to
      11.19) with 1-year mortality were similar compared with STS score (OR: 5.47, 95%
      CI: 1.48 to 20.22) and EuroSCORE (OR: 4.02, 95% CI: 0.86 to 18.70). Similar
      results were found for 30-day mortality and MACCE. Bivariable analyses, including
      STS score or EuroSCORE suggested independent associations of MGA-based scores
      (e.g., OR of frailty index: 3.29, 95% CI: 1.06 to 10.15, for 1-year mortality in
      a model including EuroSCORE). CONCLUSIONS: This study provides evidence that risk
      prediction can be improved by adding MGA-based information to global risk scores.
      Larger studies are needed for the development and validation of improved risk
      prediction models.

PMID- 22625187
TI  - Frailty scores and the writing on the wall.

PMID- 22625189
TI  - Post-dilating transcatheter heart valves.

PMID- 22625188
TI  - Predictive factors, efficacy, and safety of balloon post-dilation after
      transcatheter aortic valve implantation with a balloon-expandable valve.
AB  - OBJECTIVES: This study sought to evaluate the predictive factors, effects, and
      safety of balloon post-dilation (BPD) for the treatment of significant
      paravalvular aortic regurgitation (AR) after transcatheter aortic valve
      implantation (TAVI). BACKGROUND: Very few data exist on BPD after TAVI with a
      balloon-expandable valve. METHODS: A total of 211 patients who underwent TAVI
      with a balloon-expandable valve were included. BPD was performed after TAVI if
      paravalvular AR >= 2 was identified by transesophageal echocardiography. Clinical
      events and echocardiographic data were prospectively recorded, and median follow
      up was 12 (6 to 24) months. RESULTS: BPD was performed in 59 patients (28%),
      leading to a reduction in at least 1 degree of AR in 71% of patients, with
      residual AR <2 in 54% of the patients. The predictors of the need for BPD were
      the degree of valve calcification and transfemoral approach, with valve
      calcification volume >2,200 and >3,800 mm(3) best determining the need for and a
      poor response to BPD, respectively. Patients who underwent BPD had a higher
      incidence of cerebrovascular events at 30 days (11.9% vs. 2.0%, p = 0.006), with
      most (83%) events within the 24 h after the procedure occurring in patients who
      had BPD. No significant changes in valve area or AR degree were observed at
      follow-up in BPD and no-BPD groups. CONCLUSIONS: BPD was needed in about one
      fourth of the patients undergoing TAVI with a balloon-expandable valve and was
      successful in about one-half of them. A higher degree of valve calcification and
      transfemoral approach predicted the need for BPD. BPD was not associated with any
      deleterious effect on valve function at mid-term follow-up, but a higher rate of
      cerebrovascular events was observed in patients who had BPD.

PMID- 22625190
TI  - Percutaneous management of vascular complications in patients undergoing
      transcatheter aortic valve implantation.
AB  - OBJECTIVES: This study sought to investigate the feasibility and safety of
      percutaneous management of vascular complications after transcatheter aortic
      valve implantation (TAVI). BACKGROUND: Vascular complications after TAVI are
      frequent and outcomes after percutaneous management of these adverse events not
      well established. METHODS: Between August 2007 and July 2010, 149 patients
      underwent transfemoral TAVI using a percutaneous approach. We compared outcomes
      of patients undergoing percutaneous management of vascular complications with
      patients free from vascular complications and performed duplex ultrasonography,
      fluoroscopy, and multislice computed tomography during follow-up. RESULTS: A
      total of 27 patients (18%) experienced vascular complications consisting of
      incomplete arteriotomy closure (n = 19, 70%), dissection (n = 3, 11%), arterial
      perforation (n = 3, 11%), arterial occlusion (n = 1, 4%), and pseudoaneurysm (n =
      1, 4%). Percutaneous stent graft implantation was successful in 21 of 23 (91%)
      patients, whereas 2 patients were treated by manual compression, 2 patients
      underwent urgent surgery, and 2 patients required delayed surgery. Rates of major
      adverse cardiac events at 30 days were similar among patients undergoing
      percutaneous management of vascular complications and those without vascular
      complications (9% vs. 8%, p = 1.00). After a median follow-up of 10.9 months,
      imaging showed no evidence of hemodynamically significant stenosis (mean peak
      velocity ratio: 1.2 +/- 0.4). Stent fractures were observed in 4 stents (22%,
      type I [6%], type II [16%]) and were clinically silent in all cases. CONCLUSIONS:
      Vascular complications after TAVI can be treated percutaneously as a bailout
      procedure with a high rate of technical success, and clinical outcomes are
      comparable to patients without vascular complications. Stent patency is high
      during follow-up, although stent fractures require careful scrutiny.

PMID- 22625191
TI  - Structural integrity of balloon-expandable stents after transcatheter aortic
      valve replacement: assessment by multidetector computed tomography.
AB  - OBJECTIVES: This study sought to evaluate the structural integrity of balloon
      expandable stents used in transcatheter aortic valve replacement. BACKGROUND:
      Underexpansion, deformation, or fracture of stent frames may affect transcatheter
      heart valve (THV) function and durability. METHODS: Patients >1 year after
      transcatheter aortic valve replacement underwent multidetector computed
      tomography. Geometry of the stent frame was assessed for circularity;
      eccentricity; minimum and maximum external diameter; and expansion at the inflow,
      mid-stent, and outflow levels, as well as for stent fracture. THV noncircularity
      was defined as stent eccentricity >10% (1 - minimum diameter/maximum diameter)
      and THV underexpansion when expansion <90% (multidetector computed tomography
      derived external valve area/nominal external valve area). Echocardiography was
      performed after implantation and annually. RESULTS: Fifty patients underwent
      multidetector computed tomography at an average of 2.5 +/- 0.9 years after
      transcatheter aortic valve replacement (35 Sapien, 8 Sapien XT, and 7 Cribier
      Edwards valves [all Edwards Lifesciences, Irvine, California). The mean external
      diameter for the 23- and 26-mm valves was 23.3 +/- 0.9 mm and 25.9 +/- 0.9 mm,
      respectively. Circularity was present in 96% (48 of 50) and median eccentricity
      was 2.0% (interquartile range: 1.2% to 3.0%). Mean THV expansion was 104.1 +/-
      7.4%, which increased from stent inflow to outflow (100.8 +/- 7.6% vs. 108.1 +/-
      6.9%, p < 0.001). Stent fracture was not observed. Underexpanded valves (8% [4 of
      50]) and noncircular valves (4% [2 of 50]) demonstrated stable hemodynamic
      function on annual echocardiography. CONCLUSIONS: Balloon-expandable aortic
      valves have excellent rates of circularity with low eccentricity and maintain
      full expansion without stent fracture at an average 2.5 years after implantation.

PMID- 22625192
TI  - Factors predicting and having an impact on the need for a permanent pacemaker
      after CoreValve prosthesis implantation using the new Accutrak delivery catheter
      system.
AB  - OBJECTIVES: The purpose of this study was to evaluate the need for a permanent
      pacemaker after transcatheter aortic valve implantation with the CoreValve
      prosthesis (Medtronic, Inc., Minneapolis, Minnesota) using the new Accutrak
      delivery system (Medtronic, Inc.). BACKGROUND: The need for a permanent pacemaker
      is a recognized complication after transcatheter aortic valve implantation with
      the CoreValve prosthesis. METHODS: Between April 23, 2008 and May 31, 2011, 195
      consecutive patients with symptomatic aortic valve stenosis underwent
      transcatheter aortic valve implantation using the self-expanding CoreValve
      prosthesis. In 124 patients, the traditional delivery system was used, and in 71
      patients, the Accutrak delivery system was used. RESULTS: There were no
      significant differences in baseline electrocardiographic characteristics between
      the traditional system and the Accutrak patients: PR interval: 153 +/- 46 mm
      versus 165 +/- 30 mm, p = 0.12; left bundle branch block: 22 (20.2%) versus 8
      (12.7%), p = 0.21; right bundle branch block: 21 (19.3%) versus 8 (12.7%), p =
      0.26. The depth of the prosthesis in the left ventricular outflow tract was
      greater with the traditional system than with the Accutrak system (9.6 +/- 3.2 mm
      vs. 6.4 +/- 3 mm, p < 0.001) and the need for a permanent pacemaker was higher
      with traditional system than with Accutrak (35.1% vs. 14.3%, p = 0.003). The
      predictors of the need for a pacemaker were the depth of the prosthesis in the
      left ventricular outflow tract (hazard ratio [HR]: 1.2, 95% confidence interval
      [CI]: 1.08 to 1.34, p < 0.001), pre-existing right bundle branch block (HR: 3.5,
      95% CI: 1.68 to 7.29, p = 0.001), and use of the traditional system (HR: 27, 95%
      CI: 2.81 to 257, p = 0.004). CONCLUSIONS: The new Accutrak delivery system was
      associated with less deep prosthesis implantation in the left ventricular outflow
      tract, which could be related to the lower rate of permanent pacemaker
      requirement.

PMID- 22625193
TI  - Need for permanent pacemaker as a complication of transcatheter aortic valve
      implantation and surgical aortic valve replacement in elderly patients with
      severe aortic stenosis and similar baseline electrocardiographic findings.
AB  - OBJECTIVES: The aim of this study was to compare the incidence and predictive
      factors of complete atrioventricular block (AVB) and permanent pacemaker
      implantation (PPI) after transcatheter aortic valve implantation (TAVI) versus
      surgical aortic valve replacement (SAVR). BACKGROUND: No data exist on the need
      for PPI after TAVI versus SAVR in patients with similar baseline
      electrocardiographic (ECG) findings. METHODS: A total of 411 patients with severe
      aortic stenosis (AS) and no prior pacemaker who underwent TAVI with the balloon
      expandable Edwards valve (Edwards Lifesciences, Irvine, California) were matched
      (1:1) with 411 elderly patients with severe AS who underwent isolated SAVR on the
      basis of baseline ECG findings. The incidence, reasons, and predictive factors
      for PPI within 30 days after the procedure were compared between groups. RESULTS:
      Mean age was similar in both groups (p = 0.11), and the TAVI group had a higher
      Society of Thoracic Surgeons score (p < 0.001). The rate of new PPI was higher
      after TAVI (7.3%) compared with SAVR (3.4%), p = 0.014. Complete AVB and severe
      symptomatic bradycardia, respectively, were the reasons for PPI in the TAVI (5.6%
      and 1.7%, respectively) and SAVR (2.7% and 0.7%, respectively) groups (p = 0.039
      for complete AVB, p = NS for symptomatic bradycardia). The presence of baseline
      right bundle branch block was the only variable associated with PPI in the TAVI
      group (odds ratio: 8.61, 95% confidence interval: 3.14 to 23.67, p < 0.0001),
      whereas no variable was found in the SAVR group. CONCLUSIONS: Transcatheter
      aortic valve implantation was associated with a higher rate of complete AVB and
      PPI compared with SAVR in elderly patients with severe AS and similar baseline
      ECG findings. The presence of baseline right bundle branch block correlated with
      the need for PPI in the TAVI group.

PMID- 22625194
TI  - Transcatheter aortic valve implantation in patients with low-flow, low-gradient
      aortic stenosis.
AB  - OBJECTIVES: The purpose of this study was to evaluate the efficacy and outcome of
      transcatheter aortic valve implantation (TAVI) in patients with low-flow, low
      gradient aortic stenosis (LG-AS). BACKGROUND: Patients with LG-AS have a poor
      prognosis with medical treatment and a high risk for surgical aortic valve
      replacement. METHODS: Between January 2009 and June 2010, a total of 1,302
      patients underwent TAVI for severe AS and were prospectively included in the
      multicenter German TAVI registry. RESULTS: LG-AS was present in 149 patients
      (11.4%; mean age: 80.2 +/- 6.3 years). In this subgroup, the EuroSCORE was
      significantly higher (26.8 +/- 16.6 vs. 20.0 +/- 13.3; p < 0.0001) compared with
      patients with high-gradient AS (HG-AS). The procedural success rate (LG-AS: 95.3%
      vs. HG-AS: 97.5%; p = 0.13) and the rate of TAVI-associated complications were
      comparable in both groups (new pacemaker: 27.0% vs. 28.1%; p = 0.76;
      cerebrovascular events: 3.4% vs. 3.1%, p = 0.83). However, post-operative low
      output syndrome occurred more frequently in the LG-AS-group (LG-AS: 14.9% vs. HG
      AS: 5.7%, p < 0.0001), and mortality at 30 days and 1 year was significantly
      higher in this subgroup (LG-AS: 12.8% and 36.9% vs. HG-AS: 7.4% and 18.1%; p <
      0.001 and p < 0.0001, respectively). Post-operative New York Heart Association
      functional class improved, and self-assessed quality of life increased
      significantly, demonstrating a substantial benefit in the LG-AS group at 30 days
      and 1 year after TAVI. CONCLUSIONS: In high-risk patients with LG-AS, TAVI is
      associated with a significantly higher mortality at 30 days and at 1 year.
      However, long-term survivors benefit from TAVI with functional improvement and a
      significantly increased quality of life. Therefore, in view of the poor prognosis
      with medical treatment, TAVI should be considered an option in high-risk patients
      with LG-AS.

PMID- 22625195
TI  - Low-gradient, low-ejection fraction aortic stenosis: what we know and what we do
      not know.

PMID- 22625196
TI  - Multicenter evaluation of Edwards SAPIEN positioning during transcatheter aortic
      valve implantation with correlates for device movement during final deployment.
AB  - OBJECTIVES: This study sought to evaluate the exact location of Edwards SAPIEN
      (Edwards Lifesciences, Irvine, California) devices in different stages of
      implantation and to quantify possible operator-independent device movement during
      final deployment. BACKGROUND: Accurate device positioning during transcatheter
      aortic valve implantation is crucial in order to achieve optimal results.
      METHODS: This multicenter study consisted of 68 procedures with reliable
      pacemaker capture. Device positions were assessed using fluoroscopic images and
      the C-THV system (Paieon Medical, Rosh Ha'Ayin, Israel). RESULTS: The location
      after implantation was significantly higher than in the final stage of rapid
      pacing: 16.7 +/- 16.3% of device height below the plane of the lower sinus border
      versus 32.6 +/- 13.8%, p < 0.0001. Operator-independent device-center upper
      movement during final deployment was 2 +/- 1.43 mm, range: -1.3 to 4.6 mm. Device
      movement was asymmetrical, occurring more in the lower part of the device than in
      its upper part (3.2 +/- 1.4 mm vs. 0.75 +/- 1.5 mm, p < 0.001), resulting in
      device shortening. Multivariate analysis revealed that moderate and severe aortic
      valve calcification had 49% higher upward movement than mild calcification (p =
      0.03), and aortic sinus volume was negatively correlated with movement size (r = 
      0.35, p = 0.005). This movement was independent of device version (SAPIEN vs.
      SAPIEN XT), procedural access (transfemoral vs. transapical), and
      interventricular septum width. CONCLUSIONS: The final Edwards SAPIEN position is
      mostly aortic in relation to the lower sinus border. There is an operator
      independent upward movement of the device center during the final stage of
      implantation. Anticipated upward movement of the device should influence its
      positioning before final deployment.

PMID- 22625198
TI  - A permanent solution for a temporary problem: transcatheter valve-in-valve
      implantation for failed transcatheter aortic valve replacement.

PMID- 22625197
TI  - Transcatheter valve-in-valve implantation for failed balloon-expandable
      transcatheter aortic valves.
AB  - OBJECTIVES: This study sought to evaluate outcomes after implantation of a second
      transcatheter heart valve (THV-in-THV) for acute THV failure. BACKGROUND: Aortic
      regurgitation after transcatheter aortic valve replacement (TAVR) may be valvular
      due to prosthetic leaflet dysfunction or paravalvular due to poor annular
      sealing. METHODS: Patients undergoing aortic balloon-expandable TAVR at 3 centers
      were prospectively evaluated at baseline, intraprocedurally, at hospital
      discharge, and annually. RESULTS: Of 760 patients undergoing TAVR, 21 (2.8%)
      received a THV-in-THV implant due to acute, severe regurgitation. Aortic
      regurgitation was paravalvular in 18 patients and transvalvular in the remaining
      3 patients. THV-in-THV implantation was technically successful in 19 patients
      (90%) and unsuccessful in 2 patients (10%), who subsequently underwent open heart
      surgery. Mortality at 30 days and 1 year was 14.3% and 24%, respectively. After
      successful THV-in-THV, mean aortic valve gradient fell from 37 +/- 12 mm Hg to 13
      +/- 5 mm Hg (p < 0.01); aortic valve area increased from 0.64 +/- 0.14 cm(2) to
      1.55 +/- 0.27 cm(2) (p < 0.01); and paravalvular aortic regurgitation was none in
      4 patients, mild in 13 patients, and moderate in 2 patients. At 1-year follow-up,
      1 patient had moderate and the others had mild or no paravalvular leaks. The mean
      transvalvular gradient was 15 +/- 4 mm Hg, which was higher than in patients
      undergoing conventional TAVR (11 +/- 4 mm Hg, p = 0.02). CONCLUSIONS: THV-in-THV
      implantation is feasible and results in satisfactory short- and mid-term
      outcomes.

PMID- 22625199
TI  - Pathology of transcatheter valve therapy.
AB  - OBJECTIVES: This study sought to report on the pathology of transcatheter aortic
      valves explanted at early and late time points after transcatheter aortic valve
      implantation. BACKGROUND: Information on pathological findings following
      transcatheter aortic valve implantation is scarce, particularly late after
      transcatheter aortic valve implantation. METHODS: This study included 20 patients
      (13 men, median age 80 years [interquartile range: 72 to 84] years) with previous
      transcatheter aortic valve implantation with a valve explanted at autopsy (n =
      17) or surgery (n = 3) up to 30 months after implantation (10 transapical and 10
      transfemoral procedures). RESULTS: Structural valve degeneration was not seen,
      although fibrous tissue ingrowth was observed at later time points with minimal
      effects on cusp mobility in 1 case. Minor alterations in valve configuration or
      placement were observed in up to 50% of cases, but they were not accompanied by
      substantial changes in valve function or reliably associated with chest
      compressions. Vascular or myocardial injury was common, especially within 30 days
      of transcatheter aortic valve implantation (about 69%), with the latter
      associated with left coronary ostial occlusion by calcified native aortic valve
      tissue in 2 cases. Mild to severe myocardial amyloidosis was present in nearly
      33% of cases and likely played a role in the poor outcome of 3 patients.
      Endocarditis, migration of the valve, and embolization during the procedure led
      to surgical valve removal. CONCLUSIONS: Structural degeneration was not seen and
      minor alterations of valve configuration or placement did not affect valve
      function and were not reliably caused by chest compressions. Vascular or
      myocardial injury is very common early after transcatheter aortic valve
      implantation and myocardial amyloidosis represents a relatively frequent
      potentially significant comorbid condition.

PMID- 22625200
TI  - Failed valve-in-valve transcatheter aortic valve implantation.

PMID- 22625201
TI  - Radial artery occlusion: if a tree falls in the forest....

PMID- 22625203
TI  - A rose by any other name: a valve by any other method.

PMID- 22625204
TI  - First experience with transcatheter valve-in-valve implantation for a stenotic
      mitral prosthesis within the United States.

PMID- 22625205
TI  - CpG oligodeoxynucleotides discriminately enhance binding capacity of human naive
      B cells to  Hepatitis B virus  epitopes.
AB  - CpG oligodeoxynucleotides (CpG ODN) have the potential to enhance the antigen
      presenting cells function of human naive B cells. In this study, we aim to define
      the effect of CpG ODNs on the binding capacity of human naive B cells for
      different Hepatitis B virus (HBV) epitopes. Three HLA-A2 restricted epitopes were
      selected to incubate with CpG ODN-primed human naive B cells. Binding capacity
      for each epitope and expression of CD80, CD86, class I major histocompatibility
      complex (MHC), and class II MHC of naive B cells was tested, respectively, by
      flow cytometry. CpG ODNs, especially ODN 2216, enhanced the binding capacity of
      human naive B cells for HBV epitopes (p < 0.01), and induced markedly higher
      expression of CD80, CD86, class I MHC, and class II MHC. The binding capacity of
      CpG-treated naive B cells for each epitope was significantly different. In all
      the 3 subjects, CpG ODN 2216-primed naive B cells showed the highest binding
      ability for Env172-180 compared with the other epitopes with a high expression of
      co-stimulatory and MHC molecules. CpG ODN showed the potential to selectively
      enhance the binding capacity of human naive B cells for HBV epitopes. These
      results suggest new strategies for development of vaccine design.

PMID- 22625206
TI  - Exposure to farming environments in childhood and asthma and wheeze in rural
      populations: a systematic review with meta-analysis.
AB  - Asthma is a chronic respiratory disorder that has become substantially more
      common over the past decades. One environmental factor for which particularly
      strong associations with asthma and allergic diseases have been described is
      exposure to farming environments in childhood. The aim of this systematic review
      was to update and extend existing narrative reviews, test for heterogeneity of
      effect across studies, and conduct a meta-analysis to report a summary effect
      measure. Published relevant literature was searched through PubMed including all
      articles added to PubMed before September 1, 2011. Articles were included if they
      reported an epidemiological study on the exposure to a farming environment in
      childhood and subsequent wheeze or asthma. Heterogeneity of effect measures
      across studies was evaluated using Cochran's Q and I(2). Random-effects meta
      analysis was performed to summarize effect measures for various outcome
      definitions. In total, 357 retrieved abstracts revealed 52 original articles from
      39 studies with data considered for the meta-analysis. Most studies were
      conducted among children or on childhood onset of disease. Most data were
      published on doctor-diagnosed asthma or current wheeze. The meta-analysis showed
      substantial heterogeneity across studies with similar outcome definitions.
      Nonetheless, the combined effects were statistically significant and showed an
      approximate 25% lower asthma prevalence among exposed subjects compared with
      unexposed subjects. The protective 'farm-effect' on asthma was reported in
      numerous studies. Its underlying factors ought to be studied, and promising
      efforts have been already made. However, the heterogeneity of the effect across
      studies should also be investigated because whatever causes it is a potential
      threat to valid synthesis of evidence and to the detection of specific protective
      factors.

PMID- 22625208
TI  - Simultaneous determination of human and veterinary antibiotics in various
      environmental matrices by rapid resolution liquid chromatography-electrospray
      ionization tandem mass spectrometry.
AB  - A robust and sensitive analytical method is presented in which 11 classes of
      antibiotics are simultaneously extracted and determined in surface water, lagoon
      wastewater, influent, effluent, sediment, manure and sludge. Water samples with
      different volumes were adjusted to pH 3, added with 0.2g Na2EDTA and then
      extracted using Oasis hydrophilic-lipophilic balance (HLB) cartridges. Extraction
      of solid samples was carried out by a combination of ultrasonic and vortex mixing
      using a mixture of acetonitrile and citric buffer at pH 3 as the extraction
      solution. The extracts of the solid samples were then cleaned-up by a tandem
      solid phase extraction (SPE) method using a strong anion exchange cartridge (SAX)
      and a HLB cartridge, followed by analysis using rapid resolution liquid
      chromatography-tandem mass spectrometry (RRLC-MS/MS) equipped with electrospray
      ionization source. Among the 50 target compounds, the recoveries in the range of
      50-150% were obtained for 39, 40, 36, 40, 38, 33 and 36 antibiotics in the spiked
      samples of surface water, lagoon wastewater, influent, effluent, sediment, manure
      and sludge with three concentrations, respectively. Method quantification limits
      (MQLs) for the target compounds (except sulfaguanidine and sulfanilamide) were in
      the range of 0.52-5.88 ng/L, 2.36-65.8 ng/L, 1.73-20 ng/L, 1.42-9.52 ng/L, 0.64
      6.67 ng/g (except bacitracin and cloxacillin), 1.33-17.4 ng/g (except
      salinomycin, narasin, monensin, cloxacillin and novobiocin) and 1.50-28.6 ng/g
      (except salinomycin, narasin, monensin and cloxacillin) in surface water, lagoon
      wastewater, influent, effluent, sediment, manure and sludge, respectively. The
      developed analytical method was successfully applied in the determination of
      target compounds in wastewater and sludge samples from Huiyang wastewater
      treatment plants, and in ground water, lagoon wastewater, manure and sediment
      collected from a pig farm, in South China.

PMID- 22625207
TI  - Citrullination of proteins: a common post-translational modification pathway
      induced by different nanoparticles in vitro and in vivo.
AB  - AIM: Rapidly expanding manufacture and use of nanomaterials emphasize the
      requirements for thorough assessment of health outcomes associated with novel
      applications. Post-translational protein modifications catalyzed by Ca(2+)
      dependent peptidylargininedeiminases have been shown to trigger immune responses
      including autoantibody generation, a hallmark of immune complexes deposition in
      rheumatoid arthritis. Therefore, the aim of the study was to assess if
      nanoparticles are able to promote protein citrullination. MATERIALS & METHODS:
      Human A549 and THP-1 cells were exposed to silicon dioxide, carbon black or
      single-walled carbon nanotubes. C57BL/6 mice were exposed to respirable single
      walled carbon nanotubes. Protein citrullination, peptidylargininedeiminases
      activity and target proteins were evaluated. RESULTS: The studied nanoparticles
      induced protein citrullination both in cultured human cells and mouse lung
      tissues. Citrullination occurred via the peptidylargininedeiminase-dependent
      mechanism. Cytokeratines 7, 8, 18 and plectins were identified as intracellular
      citrullination targets. CONCLUSION: Nanoparticle exposure facilitated post
      translational citrullination of proteins.

PMID- 22625209
TI  - A note on the relevance of norsolorinic acid as a chemopreventive agent for the
      treatment of bladder cancer.

PMID- 22625210
TI  - Appropriate use criteria for echocardiography: new applications for a new era of
      utilization.

PMID- 22625211
TI  - Echocardiography derived valve area of the Edwards SAPIEN aortic valve
      prosthesis: new methodology is required to comply with old hemodynamic
      principles.

PMID- 22625212
TI  - Precise assessment of myocardial contractile performance in aortic regurgitation:
      biological and management implications.

PMID- 22625213
TI  - ECMO and ECHO: the evolving role of quantitative echocardiography in the
      management of patients requiring extracorporeal membrane oxygenation.

PMID- 22625215
TI  - Contraindications to extracorporeal membrane oxygenation: are there any
      absolutes?

PMID- 22625218
TI  - Teaching TEE for use in the operating room: where are things now...and where are
      we going?

PMID- 22625219
TI  - Strategic goals for 2012 & beyond.

PMID- 22625220
TI  - Rapid characterisation of flavonoids from Sophora alopecuroides L. by
      HPLC/DAD/ESI-MSn.
AB  - An HPLC/DAD/ESI-MSn method was established to characterise flavonoids in the
      seeds of Sophora alopecuroides L. All the flavonoids exhibited abundant [M-H]-
      ions, which triggered data-dependent multistage mass spectrometry fragmentations.
      Characteristic UV spectra were used to confirm flavonoid subtypes. In total, 22
      flavonoids and two phenolic compounds were detected and identified. Five of them
      were identified by comparing with reference standards, and the others were
      characterised based on the retention behaviour, multistage fragmentation feature
      and UV absorption. A total of 19 compounds were reported from S. alopecuroides
      for the first time. This method accomplished rapid profiling of flavonoid
      constituents in S. alopecuroides L.

PMID- 22625221
TI  - Plasma glycation levels are associated with severity in sepsis.
AB  - BACKGROUND: Advanced glycation end-products (AGE) have been involved in
      inflammatory diseases and may have an important role in the progression of
      symptoms. However, few studies have analysed the levels of glycated proteins in
      sepsis. In this study, we evaluated the levels of the well-known AGE (N(epsilon) 
      (carboxymethyl)lysine (CML) and N(epsilon) -(carboxyethyl)lysine (CEL)) in the
      plasma of septic patients. MATERIAL AND METHODS: Plasma from 36 patients admitted
      to an adult intensive care unit and 6 healthy controls had the levels of CML/CEL
      measured by ELISA. RESULTS: The level of AGE in plasma decreased with the
      increase of severity (1.40+/-0.46 nmol/mg of protein in sepsis, 0.58+/-0.23
      nmol/mg of protein in severe sepsis and 0.31+/-0.12 nmol/mg of protein in septic
      shock). Control plasma presented low AGE concentration (0.06+/-0.01 nmol/mg
      protein). Also, we found a decrease in plasma AGE in those patients that died at
      the end of 28 days follow-up (0.80+/-0.50 nmol/mg of protein in survivors vs.
      0.31+/-0.10 nmol/mg of protein in nonsurvivors), being associated with the renal
      component of sequential organ failure assessment (SOFA) score. In the same line,
      there was a decrease in plasma AGE with the increase in SOFA. CONCLUSIONS: Our
      data demonstrate that plasma AGE levels are inversely associated with the
      severity of sepsis and may be associated with kidney dysfunction.

PMID- 22625222
TI  - Healthier food choices as a result of the revised healthy diet programme
      Krachtvoer for students of prevocational schools.
AB  - BACKGROUND: Krachtvoer is a Dutch healthy diet programme for prevocational
      schools, developed in 2001 and revised for a broader target group in 2007, based
      on the findings of an evaluation of the first version. The goal of this study was
      to report on the short- and longer-term total and subgroup effects of the revised
      programme on students' fruit, fruit juice, breakfast, and snack consumption.
      METHODS: Schools were randomized to the experimental condition, teaching the
      Krachtvoer programme, or to the control condition teaching the regular nutrition
      lessons. Self-reported consumption of fruit, fruit juice, breakfast and snacks
      was measured at baseline directly before programme implementation, one to four
      weeks after finishing programme implementation, and after six months. Mixed
      linear and logistic regression analyses were conducted. RESULTS: In total 1117
      students of 13 experimental schools and 758 students of 11 control schools
      participated in the study. Short- and longer-term favourable intervention effects
      were found on fruit consumption (mean difference between experimental and control
      group 0.15 servings at both posttests). Regarding fruit juice consumption, only
      short-term favourable effects were revealed (mean difference between experimental
      and control group 0.05 glasses). Intervention effects on breakfast intakes were
      limited. No changes in snack frequency were reported, but students made healthier
      snack choices as a result of the programme. Some favourable as well as
      unfavourable effects occurred in subgroups of students. CONCLUSIONS: The effects
      on fruit consumption and snack choices justify the current nationwide
      dissemination of the programme. Achieving changes in breakfast consumption may,
      however, require other strategies.

PMID- 22625223
TI  - Effect of zinc supplementation on growth hormone-insulin growth factor axis in
      short Egyptian children with zinc deficiency.
AB  - BACKGROUND: The relationship between zinc (Zn) and growth hormone-insulin growth
      factor (GH-IGF) system and how Zn therapy stimulates growth in children has not
      been clearly defined in humans. Thus, we aimed to assess GH-IGF axis in short
      children with Zn deficiency and to investigate the effect of Zn supplementation
      on these parameters. METHODS: Fifty pre-pubertal Egyptian children with short
      stature and Zn deficiency were compared to 50 age-, sex-, and pubertal stage-
      matched controls. All subjects were subjected to history, auxological assessment
      and measurement of serum Zn, IGF-1, insulin growth factor binding protein-3
      (IGFBP-3); and basal and stimulated GH before and 3 months after Zn
      supplementation (50 mg/day). RESULTS: After 3 months of Zn supplementation in Zn
      deficient patients, there were significant increases in height standard deviation
      score (SDS, P = 0.033), serum Zn (P < 0.001), IGF-1 (P < 0.01), IGF-1 standard
      deviation score (SDS, P < 0.01) and IGFBP-3 (P = 0.042). Zn rose in all patients
      but reached normal ranges in 64 %, IGF-1 levels rose in 60 % but reached normal
      ranges in 40 % and IGFBP-3 levels rose in 40 % but reached reference ranges in 22
      %. Growth velocity (GV) SDS did not differ between cases and controls (p = 0.15)
      but was higher in GH-deficient patients than non-deficient ones, both having Zn
      deficiency (p = 0.03). CONCLUSION: Serum IGF-1 and IGFBP-3 levels were low in
      short children with Zn deficiency, and increased after Zn supplementation for 3
      months but their levels were still lower than the normal reference ranges in most
      children; therefore, Zn supplementation may be necessary for longer periods.

PMID- 22625225
TI  - Innovative approaches for training young carers: nurses cannot be left behind.

PMID- 22625224
TI  - Blood leukocytes from benznidazole-treated indeterminate chagas disease patients
      display an overall type-1-modulated cytokine profile upon short-term in vitro
      stimulation with Trypanosoma cruzi antigens.
AB  - BACKGROUND: Benznidazole (Bz)-chemotherapy is recommended to prevent Chagas
      disease progression, despite its limited efficacy during chronic disease.
      However, the host mechanisms underlying these benefits still remain to be
      elucidated. METHODS: In this study, we have used short-term whole blood cultures
      to describe the cytokine profile of Bz-treated Indeterminate Chagas disease
      patients-(INDt) as compared to untreated patients-(IND). RESULTS: Our findings
      showed that IND presented increased levels of IL-10+neutrophils, IL-12+ and IL
      10+ monocytes and IFN-gamma+NK-cells. Moreover, IND showed slight increase of IL
      4+CD4+T-cells and enhanced levels of IL-10+CD8+T-cells and B-cells. Additional
      analysis of cytokine Low and High producers also highlighted the presence of High
      cytokine producers within IND, including IL-10 from CD4+ T-cells and IFN-gamma
      from CD8+ T-cells, as compared to NI. The Bz-treatment lead to an overall
      cytokine down-regulation in the innate and adaptive compartments, including low
      levels of IL-12+ and IL-10+ neutrophils and monocytes, IFN-gamma+NK-cells, IL
      12+, TNF-alpha+, IFN-gamma+ and IL-5+CD4+T-cells and IL-10+B-cells, along with
      basal levels of cytokine-expressing CD8+T-cells in INDt as compared to IND. The
      in vitro antigen stimulation shifted the cytokine profile toward a type 1
      modulated profile, with increased levels of IL-12+ and IL-10+ monocytes, IFN
      gamma+ and IL-4+NK-cells along with TNF-alpha+ and IFN-gamma+CD8+T-cells.
      Analysis of Low and High cytokine producers, upon in vitro antigen stimulation,
      further confirm these data. CONCLUSION: Together, our findings showed that the Bz
      treatment of Indeterminate Chagas' disease patients shifts the cytokine patterns
      of peripheral blood monocytes, NK-cells and CD8+ T-cells towards a long-lasting
      Type-1-modulated profile that could be important to the maintenance of a non
      deleterious immunological microenvironment.

PMID- 22625226
TI  - Diseases of north European wrasse (Labridae) and possible interactions with
      cohabited farmed salmon, Salmo salar L.
AB  - There have been several reported studies of wrasse health but none of these has
      shown transmission of wrasse diseases when stocked with farmed Atlantic salmon.
      Most of the studies have focussed on bacterial and parasite issues, including
      treatment of bacterial diseases with antibiotics and vaccination of wrasse.
      Classical and atypical furunculosis have been reported in wrasse following
      stress, and wrasse have been susceptible to vibrio infection. Further study is
      required on the vaccination of wrasse for furunculosis with latent carrier status
      to maximize survival. There are studies on viral diseases such as infectious
      pancreatic necrosis, infectious salmon anaemia and pancreas disease and although
      these did not give any undue concern for salmon health, there is also scope for
      further study in this area. Resident parasite communities of wrasse are largely
      host-specific and do not appear to be a threat to salmon. Given that wrasse have
      not, to date, been a vector of disease in salmon, attention should be placed on
      maintaining best practice in cohabiting wrasse with salmon. Other issues that
      should be addressed are good welfare of wrasse in pens and identifying measures
      of this, the identification of losses of wrasse in pens, being alert to potential
      emerging diseases through health screening of mortalities and assessing the risks
      associated with carrying forward wrasse from one salmon production cycle to the
      next. Issues of exploitation by fishing on wild wrasse stocks and improved
      biosecurity may be addressed by the increased movement by the industry to the
      stocking of farmed wrasse.

PMID- 22625227
TI  - Distribution, clinicopathologic features and survival of breast cancer subtypes
      in Southern China.
AB  - Breast cancer research and treatment by different subtypes is an inevitable
      trend. We investigated the clinicopathologic features and outcomes of different
      breast cancer subtypes in Southern China. A total of 5809 patients with invasive
      ductal carcinomas were identified. Immunohistochemical (IHC) markers for estrogen
      receptor (ER), progesterone receptor (PR), Her2/neu, and Ki-67 proliferation
      index were used to classify cases into five molecular subtypes. Clinicopathologic
      characteristics and survival rates were analyzed retrospectively. Of all
      patients, 31.1% were luminal A subtype, 30.4% luminal B (high Ki-67), 13.1%
      luminal B (Her2/neu+), 9.0% Her2/neu and 16.5% triple negative subtype. Luminal B
      (high Ki-67) presented primarily in premenopausal patients with the lowest
      average age (43.0 years). Her2/neu positive tumors were more closely associated
      with aggressive features including increased tumor size, positive lymph node
      status and lymphvascular invasion (LVI). Triple negative subtype was
      characterized by poorer histologic grade. Her2/neu positive cases had presented
      the worst 5-year disease-free survival (DFS) and overall survival (OS).
      Multivariate analyses of OS and DFS suggested that there were different negative
      prognostic factors for the five subtypes. The benefit of the cyclophosphamide,
      methotrexate, and 5-fluorouracil (5FU) (CMF) regimen was equal to that of
      anthracycline-based and Taxane-based regimens for patients with luminal A subtype
      and triple negative subtype, but inferior to anthracycline-based and Taxane-based
      regimens for those with two luminal B subtypes and Her2/neu subtype. The
      prognostic significance of traditional markers may differ among subtypes. This
      study revealed the distinct clinicopathologic characteristics, systemic therapy
      benefits, prognostic factors and survival rate among different breast cancer
      subtypes.

PMID- 22625406
TI  - Light-induced alteration of c-di-GMP level controls motility of Synechocystis sp.
      PCC 6803.
AB  - Cph2 from the cyanobacterium Synechocystis sp. PCC 6803 is a hybrid photoreceptor
      that comprises an N-terminal module for red/far-red light reception and a C
      terminal module switching between a blue- and a green-receptive state. This
      unusual photoreceptor exerts complex, light quality-dependent control of the
      motility of Synechocystis sp. PCC 6803 cells by inhibiting phototaxis towards
      blue light. Cph2 perceives blue light by its third GAF domain that bears all
      characteristics of a cyanobacteriochrome (CBCR) including photoconversion between
      green- and blue-absorbing states as well as formation of a bilin species
      simultaneously tethered to two cysteines, C994 and C1022. Upon blue light
      illumination the CBCR domain activates the subsequent C-terminal GGDEF domain,
      which catalyses formation of the second messenger c-di-GMP. Accordingly,
      expression of the CBCR-GGDEF module in Deltacph2 mutant cells restores the blue
      light-dependent inhibition of motility. Additional expression of the N-terminal
      Cph2 fragment harbouring a red/far-red interconverting phytochrome fused to a c
      di-GMP degrading EAL domain restores the complex behaviour of the intact Cph2
      photosensor. c-di-GMP was shown to regulate flagellar and pili-based motility in
      several bacteria. Here we provide the first evidence that this universal
      bacterial second messenger is directly involved in the light-dependent regulation
      of cyanobacterial phototaxis.

PMID- 22625407
TI  - Trends in breastfeeding: it is not only at the breast anymore.
AB  - The past characterisations of breastfeeding as being only at the breast of the
      mother may no longer be applicable in the United States as mothers now frequently
      express their milk. We conducted a retrospective cohort study with women who
      visited the Cincinnati Children's Breastfeeding Medicine Clinic to understand
      breast milk feeding behaviours of healthy mothers and infants, which included
      questions specifically about breast milk expression. All 40 mothers in the cohort
      expressed their milk and all 40 infants were fed expressed milk. One infant was
      fed another mother's milk for 30 days. Two-thirds (13/40) of infants received
      their mother's expressed milk at least a week after it was first expressed and
      25% (10/40) of infants continued to be fed expressed breast milk after mothers
      had stopped expressing milk. There were 14 sequences of breast milk production by
      the mothers and 16 sequences of consumption by the infants. Early in the post
      partum period, mothers started expressing milk even though their infants were
      consuming all of the breast milk that they needed at the breast. As a result of
      breast milk expression by all mothers in this cohort, we observed highly variable
      patterns of maternal breast milk production and infant breast milk consumption,
      which were not necessarily synchronous within a dyad. It is now time to develop
      appropriate ways to characterise the production and consumption of breast milk
      more accurately and investigate whether these behaviours have consequences for
      the health of mothers and infants.

PMID- 22625408
TI  - Electronic structure and exciton-phonon interaction in two-dimensional colloidal
      CdSe nanosheets.
AB  - We study the electronic structure of ultrathin zinc-blende two-dimensional (2D)
      CdSe nanosheets both theoretically, by Hartree-renormalized k.p calculations
      including Coulomb interaction, and experimentally, by temperature-dependent and
      time-resolved photoluminescence measurements. The observed 2D-heavy hole exciton
      states show a strong influence of vertical confinement and dielectric screening.
      A very weak coupling to phonons results in a low phonon-contribution to the
      homogeneous line-broadening. The 2D-nanosheets exhibit much narrower ensemble
      absorption and emission linewidths as compared to the best colloidal CdSe
      nanocrystallites ensembles. Since those nanoplatelets can be easily stacked and
      tend to roll up as they are large, we see a way to form new types of multiple
      quantum wells and II-VI nanotubes, for example, for fluorescence markers.

PMID- 22625409
TI  - Exploratory combustion synthesis: amorphous indium yttrium oxide for thin-film
      transistors.
AB  - We report the implementation of amorphous indium yttrium oxide (a-IYO) as a thin
      film transistor (TFT) semiconductor. Amorphous and polycrystalline IYO films were
      grown via a low-temperature solution process utilizing exothermic "combustion"
      precursors. Precursor transformation and the IYO films were analyzed by
      differential thermal analysis, thermogravimetric analysis, X-ray diffraction,
      atomic force microscopy, X-ray photoelectron spectroscopy, and optical
      transmission, which reveal efficient conversion to the metal oxide lattice and
      smooth, transparent films. a-IYO TFTs fabricated with a hybrid nanodielectric
      exhibit electron mobilities of 7.3 cm(2) V(-1) s(-1) (T(anneal) = 300  degrees C)
      and 5.0 cm(2) V(-1) s(-1) (T(anneal) = 250  degrees C) for 2 V operation.

PMID- 22625410
TI  - Chemistry and biology of indoles and indazoles: a mini-review.
AB  - The present review article is related with the method of preparation, importance
      and medicinal application of indole and indazoles. The studies of heterocycles is
      an evergreen field in the branch of organic chemistry and always attract the
      attention of chemists working not only in the area of natural products but also
      in the synthetic chemistry. Moreover many useful drugs have emerged from the
      successful investigation carried out in this branch. The derivatives of indoles
      and indazoles exhibits antibacterial, anticancer, antionidants, anti
      inflammatory, antidiabetic, antiviral, atniproliferative, antituberculosis,
      antispermetogenic activity, antipsychotic drugs etc. 

PMID- 22625411
TI  - Recent advances in medicinal chemistry of sulfonamides. Rational design as anti
      tumoral, anti-bacterial and anti-inflammatory agents.
AB  - Now-a-days, cancer is becoming one of the major problems of public health in the
      world. Pharmacology treatment is a way to increase quality and long life.
      Predominantly, in last decade sulfonamide derivatives have been described as
      potential carbonic anhydrase inhibitors. In the present work, we describe recent
      advances during the last decade in medicinal chemistry of sulfonamides
      derivatives with some examples of rational design as anti-tumoral, antibacterial
      and anti-inflammatory agents. We show strategy design, structure-activity
      relationship, biological activity and advances of new sulfonamide compounds that
      have more health significance than some clinically used sulfonamides.

PMID- 22625412
TI  - A review of antimycobacterial drugs in development.
AB  - The needs of newly developed antitubercular agents are required for the control
      of tuberculosis in the present time. In the discovery of new antitubercular
      drugs, the emergence of multidrug-resistant (MDR) and extensively drug resistant
      (XDR) strains of Mycobacterium tuberculosis (Mtb) has encouraged the researchers
      to intensify the efforts to discover novel antitubercular drugs. These novel
      drugs will predominantly target the persistent state of mycobacterium strains,
      which are resistant to conventional drugs including non resistant mycobacterium
      strains. In the last three to four decades no new effective drug has been
      developed for the treatment of resistant tuberculosis. However, in recent years,
      the research and development programs for the control of TB, there is a lot works
      is going on to enhancement of the anti-TB activity of new drugs particularly
      against resistant mycobacterium strains. Simultaneously, practical usefulness of
      some new targets is being identified and validated for the treatment of TB. Some
      compounds are presently in clinical trials, while others are being investigated
      in an attempt to explore new compounds for the target based treatment. The
      present review provides an overview of the new anti-TB agents with different
      molecular structures that are being clinically used and advanced stages of
      preclinical as well as clinical stages and also attempted to highlight the
      efforts that are being made in the development of new drug molecules as lead anti
      TB agents.

PMID- 22625413
TI  - Reversible Michael additions: covalent inhibitors and prodrugs.
AB  - Covalent inhibition is an efficient molecular mechanism for inhibiting enzymes or
      modulating the function of proteins and is found in the action of many drugs and
      biologically active natural products. However, it is has been less appreciated
      that the formation of covalent bonds can be reversible or irreversible. This
      review focuses on biologically active compounds that are Michael acceptors and
      how the reversible nature of the Michael addition reaction influences biological
      activity and how this can be exploited in designing prodrugs.

PMID- 22625414
TI  - Invasive aspergillosis: adjunctive combination therapy.
AB  - Invasive aspergillosis remains a serious opportunistic fungal infection
      particularly in patients with a reduced immune defense such as those with
      hematological malignancies or transplant recipients. The mortality of invasive
      infections due to Aspergillus spp. is still high. The main reasons for this are
      the difficulty in diagnosing of these infections and the limited efficacy of
      antifungal agents. There is no optimal therapy for invasive aspergillosis, and
      therefore many clinicians have attempted to utilize a combination approach to
      improve outcomes. The current antifungal classes of drugs targeting the cell wall
      and cell membrane may need adjunctive agents focused on separate cellular
      pathways that can be used in combination therapy to maximize the efficacy, a
      valuable alternative to the monotherapy. The endeavor of this article is to
      review the literature on combination therapy by using adjunctive agents against
      Aspergillus spp and assess its eventual usability in the treatment of invasive
      aspergillosis.

PMID- 22625415
TI  - Some clinical applications of the electrochemical biosensors.
AB  - Electrochemical biosensing, due to its sensitivity and specificity, combined with
      the low-cost and operation convenience of the equipment, is considered as a
      promising point-of-care approach in clinical analysis. This review presents the
      basic principles of operation, the current status, and the trends in the
      development and the clinical implementation of some selected electrochemical
      biosensors. These include: electrochemical glucose biosensors successfully
      applied in diabetes management, and electrochemical biosensors for
      cholinesterases and trypsin activities determination. The latter, although less
      common, demonstrate the potential of improving the existing clinical methods in
      the diagnostics and the treatment of neurotoxic, neurological, and pancreatic
      diseases.

PMID- 22625416
TI  - Flax terpenoid pathway as a source of health promoting compounds.
AB  - Flax is an important crop plant grown mainly for its fiber and seeds, which are
      also rich in omega-3 fatty acids and valuable antioxidants derived from the
      terpenoid pathways including carotenoids, tocochromanols and sterols. Many of
      those components found in flax have been recently shown to positively influence
      human health. Although terpenes vary greatly in their chemical structure, mainly
      two mechanisms of their biological activity can be considered: direct
      antioxidation, and a recently explored one, connected to specific receptor and
      cell signaling pathway activation. Recent studies show that many of the health
      promoting agents derived from flax act through both of the mentioned mechanisms,
      resulting in synergistic physiological effects. The work summarizes the two
      mechanisms, focusing mainly on the one involving cell signaling, as a promising
      target for medicine and pharmacotherapy.

PMID- 22625417
TI  - Advances in studies on the rupestonic acid derivatives as anti-influenza agents.
AB  - Rupestonic acid (isolated from the Chinese traditional medicine Artemisia
      rupestris L.) is a sesquiterpene with multifunctional groups and possess higher
      activity against influenza virus B. In order to improve the biological activity
      of rupestonic acid, many derivatives have been synthesized and their anti
      influenza activity was screened. This review describes the rupestonic acid
      derivatives and their anti-influenza activity studied by our researching group.

PMID- 22625418
TI  - Role of lipid rafts/caveolae in the anticancer effect of endocannabinoids.
AB  - The endocannabinoid system comprises the cannabinoid receptors type 1 (CB1) and
      type 2 (CB2), their endogenous ligands (endocannabinoids) and the whole apparatus
      appointed of their synthesis and degradation. Recent studies investigated the
      possibility that drugs targeting the endocannabinoid system might be used to
      retard or block cancer growth. CB1, CB2 and metabolic enzymes of
      endocannabinoids, function in the context of lipid rafts, specialized membrane
      microdomains enriched in cholesterol, sphingolipids and glycosphingolipids which
      may be important in modulating signal transduction. Here, we analysed the role of
      lipid rafts/caveolae in the intracellular signaling and trafficking of
      cannabinoid receptor agonist in cancer cells. Perturbation of lipid
      rafts/caveolae may in fact represent a useful tool for the development of a novel
      therapy for endocannabinoids-related diseases, such as cancer. Also, we report
      the more recent developments of endocannabinoids in cancer drug discovery.

PMID- 22625419
TI  - Optimized and comparative antioxidant assays and its applications in herbal and
      synthetic drug analysis as an antioxidants.
AB  - Drug development in the recent times often relies on use of natural and synthetic
      drugs that are promising candidates as therapeutic agents for prevention of
      diseases and disorders. They possess different chemical structures with wide
      range of therapeutic activities. Many natural and synthetic drugs act as
      antioxidant agents in various metabolic processes. Increasing epidemiological,
      clinical and experimental studies have shown that intake of antioxidants drugs
      provide protection against various disorders and diseases related to oxidative
      stress. The factors responsible for this oxidative stress are mainly free
      radicals, reactive nitrogen species (RNS) and reactive oxygen species (ROS). The
      antioxidant drugs act as free radical scavenging, reducing and metal chelating
      substances; Antioxidants also show inhibition of various metabolic enzymes and
      factors responsible for inflammation. The present paper reviews different In
      vitro assays for determination of antioxidant activities (Table 1). The basic
      assays include DDPH assay, OH Scavenging assay, Reducing activity assay, TEAC
      assay, FCR assay, PRTC assay, ABTS assay, FRAP assay, ORAC assay, Ferric
      thiocynate assay, TRAP assay, Chemiluminescence assay, NBT assay, CUPRAC Assay.

PMID- 22625420
TI  - Plant-associated bacterial populations on native and invasive plant species:
      comparisons between 2 freshwater environments.
AB  - Plant-microbial interactions have been well studied because of the ecological
      importance of such relationships in aquatic systems. However, general knowledge
      regarding the composition of these biofilm communities is still evolving, partly
      as a result of several confounding factors that are attributable to plant host
      properties and to hydrodynamic conditions in aquatic environments. In this study,
      the occurrences of various bacterial phylogenetic taxa on 2 native plants, i.e.,
      mayapple (Podophyllum peltatum L.) and cow parsnip (Heracleum maximum Bartram),
      and on an invasive species, i.e., garlic mustard (Alliaria petiolata (M. Bieb.)
      Cavara & Grande), were quantitatively examined using nucleic acid staining and
      fluorescence in situ hybridization. The plants were incubated in triplicates for
      about a week within the Kalamazoo River and Pierce Cedar Creek as well as in
      microcosms. The bacterial groups targeted for enumeration are known to globally
      occur in relatively high abundance and are also ubiquitously distributed in
      freshwater environments. Fluorescence in situ hybridization analyses of the
      bacterioplankton assemblages revealed that the majority of bacterial cells that
      hybridized with the different probes were similar between the 2 sites. In
      contrast, the plant-associated populations while similar on the 3 plants
      incubated in Kalamazoo River, their representations were highest on the 2 native
      plants relative to the invasive species in Pierce Cedar Creek. Overall, our
      results further suggested that epiphytic bacterial assemblages are probably under
      the influences of and probably subsequently respond to multiple variables and
      conditions in aquatic milieus.

PMID- 22625421
TI  - Natural variation in GL1 and its effects on trichome density in Arabidopsis
      thaliana.
AB  - The ultimate understanding of how biological diversity arises, is maintained, and
      lost depends on identifying the genes responsible. Although a good deal has been
      discovered about gene function over the past few decades, far less is understood
      about gene effects, that is, how natural variation in a gene contributes to
      natural variation in phenotypes. Trichome density in Arabidopsis thaliana is an
      ideal trait for studies of natural molecular and phenotypic variation, as
      trichome initiation is genetically well-characterized and trichome density is
      highly variable in and among natural populations. Here, we show that variation at
      GLABRA1 (GL1), an R2R3 MYB transcription factor gene, which has a role in
      trichome initiation, has qualitative and likely quantitative effects on trichome
      density in natural accessions of A. thaliana. Specifically, we characterize four
      independent loss-of-function alleles for GL1, each of which yields a glabrous
      phenotype. Further, we find that a pattern of common polymorphisms confined to
      the GL1 locus is associated with quantitative variation for trichome density.
      While mutations resulting in a glabrous phenotype are primarily coding changes,
      the pattern resulting in quantitative variation spans both coding and regulatory
      regions. These data show that GL1 is an important source of trichome density
      variation within A. thaliana and, along with recent reports, suggest that the
      TTG1 epidermal cell fate pathway generally may be the key molecular genetic
      source of natural trichome density variation and an important model for the study
      of molecular evolution.

PMID- 22625423
TI  - Low maternal vitamin B12 status during pregnancy is associated with reduced heart
      rate variability indices in young children.
AB  - Vitamin B12 plays a vital role in neuronal development, particularly in
      myelinogenesis. Demyelination of the autonomic nervous system occurs early in
      vitamin B12 deficiency. However, the impact of maternal vitamin B12 deficiency
      during pregnancy on neuronal function in the offspring is poorly documented. The
      objective of this study was to assess cardiac autonomic nervous activity in
      children born to mothers with low vitamin B12 status during pregnancy using heart
      rate variability (HRV) indices in the frequency domain. Seventy-nine healthy
      children between 3 and 8 years of age were evaluated from an ongoing birth
      cohort. The blood sample of the mother had been stored and was analysed for
      plasma vitamin B12 following enrolment of the child. Subjects were divided, based
      on the median maternal first trimester vitamin B12 status (114 pmol L(-1)), into
      lower (n = 40) and higher (n = 39) vitamin B12 status groups. A lead II
      electrocardiogram was recorded in the supine posture and subjected to HRV
      analysis. Low-frequency HRV in absolute units was reduced significantly in
      children of the lower vitamin B12 status group (P = 0.03) and was 53% that of the
      higher vitamin B12 status group. There was a significant association between low
      frequency and total power HRV with cord blood vitamin B12 levels (rho = 0.31 and
      0.30, both P = 0.03). In summary, children born to mothers with a lower vitamin
      B12 status have a reduced cardiac sympathetic activity. The long-term implication
      of this needs to be evaluated by follow-up studies.

PMID- 22625422
TI  - Cannabidiol for neurodegenerative disorders: important new clinical applications
      for this phytocannabinoid?
AB  - Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous
      disorders exerted through molecular mechanisms that are yet to be completely
      identified. CBD acts in some experimental models as an anti-inflammatory,
      anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent,
      and is therefore a potential medicine for the treatment of neuroinflammation,
      epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia,
      respectively. The neuroprotective potential of CBD, based on the combination of
      its anti-inflammatory and anti-oxidant properties, is of particular interest and
      is presently under intense preclinical research in numerous neurodegenerative
      disorders. In fact, CBD combined with Delta(9)-tetrahydrocannabinol is already
      under clinical evaluation in patients with Huntington's disease to determine its
      potential as a disease-modifying therapy. The neuroprotective properties of CBD
      do not appear to be exerted by the activation of key targets within the
      endocannabinoid system for plant-derived cannabinoids like Delta(9)
      tetrahydrocannabinol, i.e. CB(1) and CB(2) receptors, as CBD has negligible
      activity at these cannabinoid receptors, although certain activity at the CB(2)
      receptor has been documented in specific pathological conditions (i.e. damage of
      immature brain). Within the endocannabinoid system, CBD has been shown to have an
      inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of
      FAAH enzyme), thereby enhancing the action of these endogenous molecules on
      cannabinoid receptors, which is also noted in certain pathological conditions.
      CBD acts not only through the endocannabinoid system, but also causes direct or
      indirect activation of metabotropic receptors for serotonin or adenosine, and can
      target nuclear receptors of the PPAR family and also ion channels.

PMID- 22625424
TI  - A ligand-free Pd-catalyzed cascade reaction: an access to the highly diverse
      isoquinolin-1(2H)-one derivatives via isocyanide and Ugi-MCR synthesized amide
      precursors.
AB  - A novel ligand-free palladium-catalyzed cascade reaction for the synthesis of
      highly diverse isoquinolin-1(2H)-one derivatives from isocyanide and amide
      precursors synthesized by Ugi-MCR has been developed. A broad variety of acids,
      amines, and isocyanides were used as starting materials for Ugi-MCR leading to
      various amide precursors, which in turn provided entry into diverse isoquinolin
      1(2H)-one derivatives. The reaction proceeds through tandem isocyanide insertion
      with intramolecular cyclization followed by a Mazurciewitcz-Ganesan type sequence
      to provide isoquinoline-1(2H)-one derivatives in moderate to good yields.

PMID- 22625425
TI  - Directionality and bipolarity of olfactory ensheathing cells on electrospun
      nanofibers.
AB  - AIM: As a preliminary to the construction of olfactory ensheathing cells (OECs)
      bearing scaffold for bridging larger lesions in the spinal cord, we have
      investigated the response of purified cultured OECs to nanoscale fibers of
      varying diameter using US FDA-approved, biodegradable poly(lactic-co-glycolic
      acid). MATERIALS & METHODS: Conventional electrospinning produced fibers of
      approximately 700 nm diameter (nano-700) while nanocomposite electrospinning with
      quantum dots produced significantly more uniform fibers of a reduced diameter to
      approximately 237 nm (nano-250). OECs from adult rat were FACS purified, cultured
      at low density on either a flat surface or a meshwork of randomly orientated nano
      700 and nano-250 fibers, and assessed using cytomorphometric analysis of
      immunofluorescent confocal images and by scanning electron microscopy. RESULTS &
      CONCLUSION: Compared with a flat surface, culture on a nano-700 mesh increases
      cell attachment. Cells change from rounded to stellate forms in random
      orientation. Further size reduction to the nano-250 favors bipolarity in cells
      with unidirectional orientation as observed in the case when transplanted OECs
      were used to bridge areas of damage in rat spinal cords.

PMID- 22625426
TI  - Excess body fat in obese and normal-weight subjects.
AB  - Excess body adiposity, especially abdominal obesity and ectopic fat accumulation,
      are key risk factors in the development of a number of chronic diseases. The
      advent of in vivo imaging methodologies that allow direct assessment of total
      body fat and its distribution have been pivotal in this process. They have helped
      to identify a number of sub-phenotypes in the general population whose metabolic
      risk factors are not commensurate with their BMI. At least two such sub
      phenotypes have been identified: subjects with normal BMI, but excess intra
      abdominal (visceral) fat (with or without increased ectopic fat) and subjects
      with elevated BMI (> 25 kg/m(2)) but low visceral and ectopic fat. The former sub
      phenotype is associated with adverse metabolic profiles, while the latter is
      associated with a metabolically normal phenotype, despite a high BMI. Here,
      examples of these phenotypes are presented and the value of carrying out enhanced
      phenotypical characterisation of subjects in interventional studies discussed.

PMID- 22625427
TI  - Decreased expression of zinc-alpha2-glycoprotein in hepatocellular carcinoma
      associates with poor prognosis.
AB  - BACKGROUND: Zinc-alpha2-glycoprotein (AZGP1, ZAG) was recently demonstrated to be
      an important factor in tumor carcinogenesis. However, AZGP1 expression in
      hepatocellular carcinoma (HCC) and its significance remain largely unknown.
      METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied
      to determine mRNA level of AZGP1 in 20 paired fresh HCC tissues. Clinical and
      pathological data of 246 HCC patients were collected. Tissue-microarray-based
      immunohistochemistry (IHC) was performed to examine AZGP1 expression in HCC
      samples. Relationship between AZGP1 expression and clinicopathological features
      was analyzed by Chi-square test, Kaplan-Meier analysis and Cox proportional
      hazards regression model. RESULTS: AZGP1 expression was significantly lower in
      80.0% (16/20) of tumorous tissues than that in the corresponding adjacent
      nontumorous liver tissues (P < 0.001). Consistently, IHC data revealed that
      decreased expression of AZGP1 was present in 80.1% (197/246) of HCC patient
      tissues (P < 0.001). Furthermore, AZGP1 expression in HCC significantly
      associated with several clinicopathological parameters, including serum AFP level
      (P = 0.013), liver cirrhosis (P = 0.002) and tumor differentiation (P = 0.025).
      Moreover, HCC patients with high AZGP1 expression survived longer, with better
      overall survival (P = 0.006) and disease-free survival (P = 0.025). In addition,
      low AZGP1 expression associated with worse relapse-free survival (P = 0.046) and
      distant metastatic progression-free survival (P = 0.036). CONCLUSION: AZGP1 was
      downregulated in HCC and could be served as a promising prognostic marker for HCC
      patients.

PMID- 22625428
TI  - Synthesis and anticonvulsant activity of some 4-nitro-N-phenylbenzamides.
AB  - A short series of 4-nitro-N-phenylbenzamides was synthesized and evaluated for
      anticonvulsant properties and neurotoxicity. In mice dosed intraperitoneally,
      three of the four 4-nitro-N-phenylbenzamides were efficient in the maximal
      electroshock-induced seizure (MES) test, especially N-(2,6-dimethylphenyl)-4
      nitrobenzamide (ED(50) value in the MES test = 31.8 MUmol/kg, TD(50) = 166.9
      MUmol/kg, protective index [PI] = 5.2) and N-(2-chloro-6-methylphenyl)-4
      nitrobenzamide (ED(50) value in the MES test = 90.3 MUmol/kg, TD(50) = 1.068
      MUmol/kg, PI = 11.8). The latter 4-nitro-N-phenylbenzamide was also found to be
      active against seizures induced by subcutaneous pentylenetetrazole (sc Ptz) and
      was selected for further evaluation in rats dosed orally. In these conditions, N
      (2-chloro-6-methylphenyl)-4-nitrobenzamide was found to be, in the MES test,
      three times more active than phenytoin and 4-amino-N-(2,6
      dimethylphenyl)benzamide, two potent anti-MES agents.

PMID- 22625430
TI  - Hb Stanleyville-II [alpha78(EF7)Asn->Lys (alpha2); HbA2: c.237C>A]: incidence of
      1:11,500 in a newborn screening program in Brazil.
AB  - Almost 3 million babies were tested in a newborn screening program in Minas
      Gerais, Brazil (1998-2008); 128 who have S-like hemoglobins (Hbs) were tested for
      the beta(S) allele and 112 were identified through polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) or sequencing. Hb
      Stanleyville-II [alpha78(EF7)Asn->Lys (alpha2); HbA2: c.237C>A] was present in 96
      children (85.7%), two in a homozygous state and 94 in a heterozygous state. Its
      estimated prevalence was 1:11,500. Hbs Hasharon [alpha47(CE5)Asp->His, GAC>CAC
      (alpha2)], Ottawa [alpha15(A13)Gly->Arg (GGT>CGT) (alpha2 or alpha1)], G-Ferrara
      [beta57(E1)Asn->Lys (AAC>AAA or AAG)], St. Luke's [alpha95(G2)Pro->Arg, C CG>C GG
      (alpha1)], Maputo [beta47(CD6)Asp->Tyr (GAT>TAT)] and Etobicoke [alpha84(F5)Ser
      >Arg (AG C>AG G or CGC or AGA) (alpha2 or alpha1)] were also identified. Many
      children with Hbs Stanleyville-II and Hasharon also co-inherited the -alpha(3.7)
      thalassemia gene. African ancestry was recognized by parents of all 31 children
      with Hb Stanleyville-II who were interviewed. Mean corpuscular volume (MCV) and
      mean corpuscular Hb (MCH) values were significantly lower in children with alpha
      thalassemia (alpha-thal). We came to the conclusion that Hb Stanleyville-II is
      not so uncommon in Brazil and seems to have originated from the African slave
      trade. This study reinforces the importance of an accurate diagnosis of variants
      that have electrophoretic mobility similar to Hb S [beta6(A3)Glu->Val, GAG>GTG]
      so that false diagnoses are avoided.

PMID- 22625429
TI  - Pichia pastoris 14-3-3 regulates transcriptional activity of the methanol
      inducible transcription factor Mxr1 by direct interaction.
AB  - The zinc-finger transcription factor, Mxr1 activates methanol utilization and
      peroxisome biogenesis genes in the methylotrophic yeast, Pichia pastoris.
      Expression of Mxr1-dependent genes is regulated in response to various carbon
      sources by an unknown mechanism. We show here that this mechanism involves the
      highly conserved 14-3-3 proteins. 14-3-3 proteins participate in many biological
      processes in different eukaryotes. We have characterized a putative 14-3-3
      binding region at Mxr1 residues 212-225 and mapped the major activation domain of
      Mxr1 to residues 246-280, and showed that phenylalanine residues in this region
      are critical for its function. Furthermore, we report that a unique and
      previously uncharacterized 14-3-3 family protein in P. pastoris complements
      Saccharomyces cerevisiae 14-3-3 functions and interacts with Mxr1 through its 14
      3-3 binding region via phosphorylation of Ser215 in a carbon source-dependent
      manner. Indeed, our in vivo results suggest a carbon source-dependent regulation
      of expression of Mxr1-activated genes by 14-3-3 in P. pastoris. Interestingly, we
      observed 14-3-3-independent binding of Mxr1 to the promoters, suggesting a post
      DNA binding function of 14-3-3 in regulating transcription. We provide the first
      molecular explanation of carbon source-mediated regulation of Mxr1 activity,
      whose mechanism involves a post-DNA binding role of 14-3-3.

PMID- 22625432
TI  - Fabrication of Fe3O4/SiO2 core/shell nanoparticles attached to graphene oxide and
      its use as an adsorbent.
AB  - Amino-functionalized Fe(3)O(4)/SiO(2) core/shell nanoparticles were synthesized
      by reacting Fe(3)O(4) nanoparticles with tetraethyl orthosilicate and (3
      aminopropyl) triethoxysilane to introduce amino groups on the surface. The amino
      groups on the Fe(3)O(4)/SiO(2) were reacted with the carboxylic groups of
      graphene oxide (GO) with the aid of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
      and N-hydroxysuccinnimide to form Fe(3)O(4)/SiO(2)GO nanoparticles. The
      structural, surface, and magnetic characteristics of the material were
      investigated by scanning and transmission electron microscopy, energy-dispersive
      X-ray spectrometry, powder X-ray diffraction, Fourier transform infrared
      spectroscopy, and thermogravimetric analysis. Adsorption equilibrium and kinetics
      of methylene blue on the Fe(3)O(4)/SiO(2)GO were studied in a batch system. The
      maximum adsorption capacities were found to be 97.0, 102.6, and 111.1 mg g(-1) at
      25, 45, and 60 degrees C, respectively. A second-order kinetic equation could
      best describe the sorption kinetics. Thermodynamic parameters indicated that the
      adsorption of methylene blue onto the material was thermodynamically feasible and
      could occur spontaneously.

PMID- 22625431
TI  - The 1027th target candidate in stroke: Will NADPH oxidase hold up?
AB  - As recently reviewed, 1026 neuroprotective drug candidates in stroke research
      have all failed on their road towards validation and clinical translation,
      reasons being quality issues in preclinical research and publication bias.
      Quality control guidelines for preclinical stroke studies have now been
      established. However, sufficient understanding of the underlying mechanisms of
      neuronal death after stroke that could be possibly translated into new therapies
      is lacking. One exception is the hypothesis that cellular death is mediated by
      oxidative stress. Oxidative stress is defined as an excess of reactive oxygen
      species (ROS) derived from different possible enzymatic sources. Among these,
      NADPH oxidases (NOX1-5) stand out as they represent the only known enzyme family
      that has no other function than to produce ROS. Based on data from different NOX
      knockout mouse models in ischemic stroke, the most relevant isoform appears to be
      NOX4. Here we discuss the state-of-the-art of this target with respect to stroke
      and open questions that need to be addressed on the path towards clinical
      translation.

PMID- 22625433
TI  - Effect of wearing a dorsiflexion assist orthosis on mobility, perceived fatigue
      and exertion during the six-minute walk test in people with multiple sclerosis: a
      randomised cross-over protocol.
AB  - BACKGROUND: Fatigue in combination with gait and balance impairments can severely
      limit daily activities in people with multiple sclerosis (PWMS). Generalised
      fatigue has a major impact on walking ability, with moderately disabled PWMS
      experiencing difficulty in walking extended distances. Localised motor fatigue in
      the ankle dorsiflexors can lead to foot drop, further reducing functional
      ambulation. The aim of this study is to evaluate the effect of a simple dynamic
      dorsiflexion assist orthosis on walking-induced fatigue, gait, balance and
      functional mobility in PWMS. METHODS: A randomised cross-over trial will be
      conducted with 40 community dwelling PWMS with mild to moderate mobility
      disability. Participants will initially be screened for disease severity,
      balance, strength, depression and fatigue at the South Australian Motion Analysis
      Centre. On two non-consecutive occasions, within two weeks, participants will
      undergo either the 6-minute walk test (6MWT) or the 6MWT while wearing a
      dorsiflexion ankle orthosis (with a randomised condition order). Distance walked,
      perceived exertion, perceived fatigue and the physiological cost of walking (the
      primary outcome measures) will be compared between the two walking conditions.
      Additional pre- and post-6MWT assessments for the two conditions will include
      tests of strength, reaction time, gait and balance. DISCUSSION: This study will
      increase our understanding of motor fatigue on gait and balance control in PWMS
      and elucidate the effect of a Dynamic Ankle Orthosis on fatigue-related balance
      and gait in PWMS. It will also examine relationships between mobility and balance
      performance with perceived fatigue levels in this group. TRIAL REGISTRATION
      NUMBER: ACTRN12612000218897.

PMID- 22625650
TI  - Carbon-deuterium bonds as probes of protein thermal unfolding.
AB  - We report a residue-specific characterization of the thermal unfolding mechanism
      of ferric horse heart cytochrome c using C-D bonds site-specifically incorporated
      at residues dispersed throughout three different structural elements within the
      protein. As the temperature increases, Met80 first dissociates from the heme
      center, and the protein populates a folding intermediate before transitioning to
      a solvent exposed state. With further increases in temperature, the C-terminal
      helix frays and then loses structure along with the core of the protein.
      Interestingly, the data also reveal that the state populated at high temperature
      retains some structure and possibly represents a molten globule. Elucidation of
      the detailed unfolding mechanism and the structure of the associated molten
      globule, both of which represent challenges to conventional techniques,
      highlights the utility of the C-D technique.

PMID- 22625651
TI  - Intermedin is overexpressed in hepatocellular carcinoma and regulates cell
      proliferation and survival.
AB  - Angiogenesis is one of the hallmarks of tumor growth and metastasis.
      Identification of tumor angiogenic factors has been a critical component in
      understanding cancer biology and treatment. Intermedin (IMD) has been reported to
      promote angiogenesis in a rat ischemic model and human umbilical vascular
      endothelial cells. Our study sought to determine the role of IMD in human
      hepatocellular carcinoma tumor progression. High IMD mRNA expression levels were
      observed in human hepatocellular carcinoma tumors, even in early stage disease,
      by real-time RT-PCR. Immunohistochemical analysis of hepatocellular carcinoma
      clinical samples demonstrated that the tumor regions were significantly more
      immunoreactive for IMD than adjacent benign liver. Inhibition of IMD expression
      using RNA interference reduced cell proliferation in SK-Hep-1 and SNU-398 cells.
      Blockage of IMD signaling using either an antagonist peptide or a neutralizing
      antibody inhibited growth in a dose-dependent manner with concomitant induction
      of apoptosis, causing cleavage of caspase-8 and downregulation of Gli1 and Bcl2.
      Conversely, addition of IMD active peptide increased the phosphorylation level of
      extracellular signal-regulated kinase. Thus, IMD might play an important role in
      cell proliferation and survival of hepatocellular carcinoma. Our data suggests
      that IMD is a potential biomarker and therapeutic target for hepatocellular
      carcinoma.

PMID- 22625653
TI  - Synthesis of ethanol via syngas on Cu/SiO2 catalysts with balanced Cu0-Cu+ sites.
AB  - This paper describes an emerging synthetic route for the production of ethanol
      (with a yield of ~83%) via syngas using Cu/SiO(2) catalysts. The remarkable
      stability and efficiency of the catalysts are ascribed to the unique lamellar
      structure and the cooperative effect between surface Cu(0) and Cu(+) obtained by
      an ammonia evaporation hydrothermal method. Characterization results indicated
      that the Cu(0) and Cu(+) were formed during the reduction process, originating
      from well-dispersed CuO and copper phyllosilicate, respectively. A correlation
      between the catalytic activity and the Cu(0) and Cu(+) site densities suggested
      that Cu(0) could be the sole active site and primarily responsible for the
      activity of the catalyst. Moreover, we have shown that the selectivity for
      ethanol or ethylene glycol can be tuned simply by regulating the reaction
      temperature.

PMID- 22625654
TI  - Design, preparation, X-ray crystal structure, and reactivity of o
      alkoxyphenyliodonium bis(methoxycarbonyl)methanide, a highly soluble carbene
      precursor.
AB  - The preparation, X-ray structure, and reactivity of new, highly soluble, and
      reactive iodonium ylides derived from malonate methyl ester and bearing an ortho
      substituent on the phenyl ring are reported. These new reagents show higher
      reactivity than common phenyliodonium ylides in the Rh-catalyzed
      cyclopropanation, C-H insertion, and transylidation reactions under homogeneous
      conditions.

PMID- 22625652
TI  - Signalling through the type 1 insulin-like growth factor receptor (IGF1R)
      interacts with canonical Wnt signalling to promote neural proliferation in
      developing brain.
AB  - Signalling through the IGF1R [type 1 IGF (insulin-like growth factor) receptor]
      and canonical Wnt signalling are two signalling pathways that play critical roles
      in regulating neural cell generation and growth. To determine whether the
      signalling through the IGF1R can interact with the canonical Wnt signalling
      pathway in neural cells in vivo, we studied mutant mice with altered IGF
      signalling. We found that in mice with blunted IGF1R expression specifically in
      nestin-expressing neural cells (IGF1RNestin-KO mice) the abundance of neural beta
      catenin was significantly reduced. Blunting IGF1R expression also markedly
      decreased: (i) the activity of a LacZ (beta-galactosidase) reporter transgene
      that responds to Wnt nuclear signalling (LacZTCF reporter transgene) and (ii) the
      number of proliferating neural precursors. In contrast, overexpressing IGF-I
      (insulin-like growth factor I) in brain markedly increased the activity of the
      LacZTCF reporter transgene. Consistently, IGF-I treatment also markedly increased
      the activity of the LacZTCF reporter transgene in embryonic neuron cultures that
      are derived from LacZTCF Tg (transgenic) mice. Importantly, increasing the
      abundance of beta-catenin in IGF1RNestin-KO embryonic brains by suppressing the
      activity of GSK3beta (glycogen synthase kinase-3beta) significantly alleviated
      the phenotypic changes induced by IGF1R deficiency. These phenotypic changes
      includes: (i) retarded brain growth, (ii) reduced precursor proliferation and
      (iii) decreased neuronal number. Our current data, consistent with our previous
      study of cultured oligodendrocytes, strongly support the concept that IGF
      signalling interacts with canonical Wnt signalling in the developing brain to
      promote neural proliferation. The interaction of IGF and canonical Wnt signalling
      plays an important role in normal brain development by promoting neural precursor
      proliferation.

PMID- 22625655
TI  - AFLP genome scans suggest divergent selection on colour patterning in allopatric
      colour morphs of a cichlid fish.
AB  - Genome scan-based tests for selection are directly applicable to natural
      populations to study the genetic and evolutionary mechanisms behind phenotypic
      differentiation. We conducted AFLP genome scans in three distinct geographic
      colour morphs of the cichlid fish Tropheus moorii to assess whether the extant,
      allopatric colour pattern differentiation can be explained by drift and to
      identify markers mapping to genomic regions possibly involved in colour
      patterning. The tested morphs occupy adjacent shore sections in southern Lake
      Tanganyika and are separated from each other by major habitat barriers. The
      genome scans revealed significant genetic structure between morphs, but a very
      low proportion of loci fixed for alternative AFLP alleles in different morphs.
      This high level of polymorphism within morphs suggested that colour pattern
      differentiation did not result exclusively from neutral processes. Outlier
      detection methods identified six loci with excess differentiation in the
      comparison between a bluish and a yellow-blotch morph and five different outlier
      loci in comparisons of each of these morphs with a red morph. As population
      expansions and the genetic structure of Tropheus make the outlier approach prone
      to false-positive signals of selection, we examined the correlation between
      outlier locus alleles and colour phenotypes in a genetic and phenotypic cline
      between two morphs. Distributions of allele frequencies at one outlier locus were
      indeed consistent with linkage to a colour locus. Despite the challenges posed by
      population structure and demography, our results encourage the cautious
      application of genome scans to studies of divergent selection in subdivided and
      recently expanded populations.

PMID- 22625656
TI  - A comparison of the accuracy of film-screen mammography, full-field digital
      mammography, and digital breast tomosynthesis.
AB  - AIM: To measure the change in diagnostic accuracy of conventional film-screen
      mammography and full-field digital mammography (FFDM) with the addition of
      digital breast tomosynthesis (DBT) in women recalled for assessment following
      routine screening. MATERIALS AND METHODS: Ethics approval for the study was
      granted. Women recalled for assessment following routine screening with screen
      film mammography were invited to participate. Participants underwent bilateral,
      two-view FFDM and two-view DBT. Readers scored each lesion separately for
      probability of malignancy on screen-film mammography, FFDM, and then DBT. The
      scores were compared with the presence or absence of malignancy based on the
      final histopathology outcome. RESULTS: Seven hundred and thirty-eight women
      participated (93.2% recruitment rate). Following assessment 204 (26.8%) were
      diagnosed as malignant (147 invasive and 57 in-situ tumours), 286 (37.68%) as
      benign, and 269 (35.4%) as normal. The diagnostic accuracy was evaluated by using
      receiving operating characteristic (ROC) and measurement of area under the curve
      (AUC). The AUC values demonstrated a significant (p = 0.0001) improvement in the
      diagnostic accuracy with the addition of DBT combined with FFDM and film-screen
      mammography (AUC = 0.9671) when compared to FFDM plus film-screen mammography
      (AUC = 0.8949) and film-screen mammography alone (AUC = 0.7882). The effect was
      significantly greater for soft-tissue lesions [AUC was 0.9905 with the addition
      of DBT and AUC was 0.9201 for FFDM with film-screen mammography combined (p =
      0.0001)] compared to microcalcification [with the addition of DBT (AUC = 0.7920)
      and for FFDM with film-screen mammography combined (AUC = 0.7843; p = 0.3182)].
      CONCLUSION: The addition of DBT increases the accuracy of mammography compared to
      FFDM and film-screen mammography combined and film-screen mammography alone in
      the assessment of screen-detected soft-tissue mammographic abnormalities.

PMID- 22625657
TI  - Competitive interactions between forest trees are driven by species' trait
      hierarchy, not phylogenetic or functional similarity: implications for forest
      community assembly.
AB  - The relative importance of competition vs. environmental filtering in the
      assembly of communities is commonly inferred from their functional and
      phylogenetic structure, on the grounds that similar species compete most strongly
      for resources and are therefore less likely to coexist locally. This approach
      ignores the possibility that competitive effects can be determined by relative
      positions of species on a hierarchy of competitive ability. Using growth data, we
      estimated 275 interaction coefficients between tree species in the French
      mountains. We show that interaction strengths are mainly driven by trait
      hierarchy and not by functional or phylogenetic similarity. On the basis of this
      result, we thus propose that functional and phylogenetic convergence in local
      tree community might be due to competition-sorting species with different
      competitive abilities and not only environmental filtering as commonly assumed.
      We then show a functional and phylogenetic convergence of forest structure with
      increasing plot age, which supports this view.

PMID- 22625658
TI  - A survey study of index food-related allergic reactions and anaphylaxis
      management.
AB  - BACKGROUND: Initial food-allergic reactions are often poorly recognized and under
      treated. METHODS: Parents of food-allergic children were invited to complete an
      online questionnaire, designed with Kids with Food Allergies Foundation, about
      their children's first food-allergic reactions resulting in urgent medical
      evaluation. RESULTS: Among 1361 reactions, 76% (95% CI 74-79%) were highly likely
      to represent anaphylaxis based on NIAID/FAAN criteria. Only 34% (95% CI 31-37%)
      of these were administered epinephrine. In 56% of these, epinephrine was
      administered by emergency departments; 20% by parents; 9% by paramedics; 8% by
      primary care physicians; and 6% by urgent care centers. In 26% of these,
      epinephrine was given within 15 min of the onset of symptoms; 54% within 30 min;
      82% within 1 h; and 93% within 2 h. Factors associated with a decreased
      likelihood of receiving epinephrine for anaphylaxis included age <12 months, milk
      and egg triggers, and symptoms of abdominal pain and/or diarrhea. Epinephrine was
      more likely to be given to asthmatic children and children with peanut or tree
      nut ingestion prior to event. Post-treatment, 42% of reactions likely to
      represent anaphylaxis were referred to allergists, 34% prescribed and/or given
      epinephrine auto-injectors, 17% trained to use epinephrine auto-injectors, and
      19% given emergency action plans. Of patients treated with epinephrine, only half
      (47%) were prescribed epinephrine auto-injectors. CONCLUSIONS: Only one-third of
      initial food-allergic reactions with symptoms of anaphylaxis were recognized and
      treated with epinephrine. Fewer than half of patients were referred to
      allergists. There is still a need to increase education and awareness about food
      induced anaphylaxis.

PMID- 22625659
TI  - Adaptive functional specialisation of architectural design and fibre type
      characteristics in agonist shoulder flexor muscles of the llama, Lama glama.
AB  - Like other camelids, llamas (Lama glama) have the natural ability to pace (moving
      ipsilateral limbs in near synchronicity). But unlike the Old World camelids
      (bactrian and dromedary camels), they are well adapted for pacing at slower or
      moderate speeds in high-altitude habitats, having been described as good climbers
      and used as pack animals for centuries. In order to gain insight into skeletal
      muscle design and to ascertain its relationship with the llama's characteristic
      locomotor behaviour, this study examined the correspondence between architecture
      and fibre types in two agonist muscles involved in shoulder flexion (M. teres
      major - TM and M. deltoideus, pars scapularis - DS and pars acromialis - DA).
      Architectural properties were found to be correlated with fibre-type
      characteristics both in DS (long fibres, low pinnation angle, fast-glycolytic
      fibre phenotype with abundant IIB fibres, small fibre size, reduced number of
      capillaries per fibre and low oxidative capacity) and in DA (short fibres, high
      pinnation angle, slow-oxidative fibre phenotype with numerous type I fibres, very
      sparse IIB fibres, and larger fibre size, abundant capillaries and high oxidative
      capacity). This correlation suggests a clear division of labour within the M.
      deltoideus of the llama, DS being involved in rapid flexion of the shoulder joint
      during the swing phase of the gait, and DA in joint stabilisation during the
      stance phase. However, the architectural design of the TM muscle (longer fibres
      and lower fibre pinnation angle) was not strictly matched with its fibre-type
      characteristics (very similar to those of the postural DA muscle). This unusual
      design suggests a dual function of the TM muscle both in active flexion of the
      shoulder and in passive support of the limb during the stance phase, pulling the
      forelimb to the trunk. This functional specialisation seems to be well suited to
      a quadruped species that needs to increase ipsilateral stability of the limb
      during the support phase of the pacing gait. Compared with other species, llama
      skeletal muscles are well suited for greater force generation combined with
      higher fatigue resistance during exercise. These characteristics are interpreted
      as being of high adaptive value, given the llama's habitat and its use as a pack
      animal.

PMID- 22625663
TI  - Socio-economic and demographic determinants of childhood obesity prevalence in
      Greece: the GRECO (Greek Childhood Obesity) study.
AB  - OBJECTIVE: Given the rapid increase in the prevalence of childhood obesity,
      identifying the sociodemographic influences on obesity status is important for
      planning and implementing effective prevention initiatives. However, this type of
      data is limited for Greek children. Therefore the aim of the present study was to
      identify possible sociodemographic factors associated with childhood obesity at
      the national level. DESIGN: Cross-sectional, population-based survey, carried out
      from October to May 2009. Setting Under the context of the GRECO (Greek Childhood
      Obesity) study, a nationwide sample of 2315 primary-school children. SUBJECTS:
      Children aged 10-12 years and their parents were voluntarily enrolled. Direct
      anthropometric measurements of the children were obtained and information on
      sociodemographic characteristics of the parents, as well as their self-reported
      values of body weight and height, were collected. RESULTS: Overweight and obesity
      prevalence was 29.5 % and 13.1 %, respectively, among boys; 29.5 % and 9.0 %,
      respectively, among girls. Multiple logistic regression analysis revealed that
      the most important sociodemographic predictors of childhood obesity were mother's
      age, parental BMI classification and father's type of occupation. More
      specifically, increased mother's age and normal BMI status of the parents seemed
      to have a protective effect on the likelihood of having an overweight/obese
      child. Additionally, the odds of a female child of being overweight/obese were
      reduced when the father's type of occupation tended to be less manual.
      CONCLUSIONS: Anti-obesity health policy interventions have to address to the
      parents and promote their active involvement, to effectively confront the
      alarming magnitude of the paediatric obesity problem in Greece.

PMID- 22625662
TI  - Meta-analysis of the comparative effects of different classes of antihypertensive
      agents on brachial and central systolic blood pressure, and augmentation index.
AB  - AIMS: Brachial systolic blood pressure (bSBP) exceeds aortic pressure by a
      variable amount, and estimated central systolic blood pressure (cSBP) may be a
      better indicator of cardiovascular risk than bSBP. We undertook a systematic
      review and meta-analysis to compare the effect of single and multiple
      antihypertensive agents on bSBP, cSBP and augmentation index (AIx). METHODS: A
      random effects meta-analysis was performed on 24 randomized controlled trials of
      antihypertensives with measurements of bSBP, cSBP and/or AIx. Separate analyses
      were performed for drug comparisons with or without placebo, and drug
      combinations. RESULTS: In the placebo vs. drug meta-analysis, antihypertensive
      therapy reduced bSBP more than cSBP and there was no statistically significant
      evidence of heterogeneity by drug class, although the number of individual
      studies was small. In placebo-adjusted drug vs. drug comparison, treatment with
      beta-blockers, omapatrilat and thiazide diuretics lowered cSBP significantly less
      than bSBP (i.e. central to brachial amplification decreased), whereas other
      monotherapies lowered cSBP and bSBP to similar extents. Sample sizes were too
      small and effect estimates insufficiently precise to allow firm conclusions to be
      made regarding comparisons between individual drug classes. Antihypertensive
      combinations that included beta-blockers decreased central to brachial
      amplification. beta-Blockers increased AIx, whereas all other antihypertensive
      agents reduced AIx to similar extents. CONCLUSIONS: A reduction in central to
      brachial amplification by some classes of antihypertensive drug will result in
      lesser reductions in cSBP despite achievement of target bSBP. This effect could
      contribute to differences in outcomes in randomized clinical trials when beta
      blocker- and/or diuretic-based antihypertensive therapy are compared with other
      regimens.

PMID- 22625664
TI  - Polyhexamethylene biguanide functionalized cationic silver nanoparticles for
      enhanced antimicrobial activity.
AB  - Polyhexamethylene biguanide (PHMB), a broad spectrum disinfectant against many
      pathogens, was used as a stabilizing ligand for the synthesis of fairly uniform
      silver nanoparticles. The particles formed were characterized using UV-visible
      spectroscopy, FTIR, dynamic light scattering, electrophoretic mobility, and TEM
      to measure their morphology and surface chemistry. PHMB-functionalized silver
      nanoparticles were then evaluated for their antimicrobial activity against a gram
      negative bacterial strain, Escherichia coli. These silver nanoparticles were
      found to have about 100 times higher bacteriostatic and bactericidal activities,
      compared to the previous reports, due to the combined antibacterial effect of
      silver nanoparticles and PHMB. In addition to other applications, PHMB
      functionalized silver nanoparticles would be extremely useful in textile industry
      due to the strong interaction of PHMB with cellulose fabrics.

PMID- 22625665
TI  - Acute experimental stress evokes a differential gender-determined increase in
      human intestinal macromolecular permeability.
AB  - BACKGROUND: Intestinal epithelial dysfunction is a common pathophysiologic
      feature in irritable bowel syndrome (IBS) patients and might be the link to its
      clinical manifestations. We previously showed that chronic psychosocial stress
      induces jejunal epithelial barrier dysfunction; however, whether this epithelial
      response is gender-specific and might thus explain the enhanced female
      susceptibility to IBS remains unknown. METHODS: Intestinal responses to acute
      stress were compared in age-matched groups of healthy women and men (n = 10 each)
      experiencing low background stress. A 20-cm jejunal segment, was perfused with an
      isosmotic solution, and intestinal effluents were collected under basal
      conditions, for 15 min during cold pain stress and for a 45-min recovery period.
      Epithelial function (net water flux and albumin output), changes in stress
      hormones, and cardiovascular and psychologic responses to cold stress were
      measured. KEY RESULTS: Heart rate and blood pressure significantly increased
      during cold pain stress with no differences between men and women.
      Adrenocorticotropic hormone and cortisol levels during cold pain stress were
      significantly higher in men. Basal net water flux and epithelial permeability
      were similar in men and women. Cold pain stress increased water flux in both
      groups (72 +/- 23 and 107 +/- 18 MUL min(-1) cm(-1) , respectively; F(5, 90) =
      5.5; P = 0.003 for Time) and, interestingly, this was associated with a marked
      increase of albumin permeability in women but not in men (0.8 +/- 0.2 vs.-0.7 +/-
      0.2 mg/15 min; P < 0.0001). CONCLUSIONS & INFERENCES: Intestinal macromolecular
      permeability in response to acute experimental stress is increased in healthy
      women, a mechanism that may contribute to female oversusceptibility to IBS.

PMID- 22625666
TI  - Hb S [beta6(A3)Glu->Val, GAG>GTG] and beta-globin gene cluster haplotype
      distribution in Mauritania.
AB  - Of 1050 Mauritanian blood donors screened from the two main racial groups, i.e.,
      the Moors and Black Africans, 60 were found to carry Hb S [beta6(A3)Glu->Val,
      GAG>GTG], giving a global frequency of 5.71%. The prevalence observed in the
      Black African Mauritanians (10.69%) is almost five times that found in the Moor
      group (2.25%). Four of the five main beta(S) haplotypes were detected in this
      study: Senegal (77.8%), Benin (8.8%), Arab-Indian (5.5%) and Bantu (4.4%). These
      data showed that Hb S is a serious public health problem in Mauritania. They also
      confirm the ethnic heterogeneity of the Mauritanian population.

PMID- 22625844
TI  - Working on wellness (WOW): a worksite health promotion intervention programme.
AB  - BACKGROUND: Insufficient PA has been shown to cluster with other CVD risk factors
      including insufficient fruit and vegetable intake, overweight, increased serum
      cholesterol concentrations and elevated blood pressure. This paper describes the
      development of Working on Wellness (WOW), a worksite intervention program
      incorporating motivational interviewing by wellness specialists, targeting
      employees at risk. In addition, we describe the evaluation the effectiveness of
      the intervention among employees at increased risk for cardiovascular disease.
      METHODS: The intervention mapping (IM) protocol was used in the planning and
      design of WOW. Focus group discussions and interviews with employees and managers
      identified the importance of addressing risk factors for CVD at the worksite.
      Based on the employees' preference for individual counselling, and previous
      evidence of the effectiveness of this approach in the worksite setting, we
      decided to use motivational interviewing as part of the intervention strategy.
      Thus, as a cluster-randomised, controlled control trial, employees at increased
      risk for CVD (N = 928) will be assigned to a control or an intervention group,
      based on company random allocation. The sessions will include motivational
      interviewing techniques, comprised of two face-to-face and four telephonic
      sessions, with the primary aim to increase habitual levels of PA. Measures will
      take place at baseline, 6 and 12 months. Secondary outcomes include changes in
      nutritional habits, serum cholesterol and glucose concentrations, blood pressure
      and BMI. In addition, healthcare expenditure and absenteeism will be measured for
      the economic evaluation. Analysis of variance will be performed to determine
      whether there were significant changes in physical activity habits in the
      intervention and control groups at 6 and 12 months. DISCUSSION: The formative
      work on which this intervention is based suggests that the strategy of targeting
      employees at increased risk for CVD is preferred. Importantly, this study extends
      the work of a previous, similar study, Health Under Construction, in a different
      setting. Finally, this study will allow an economic evaluation of the
      intervention that will be an important outcome for health care funders, who
      ultimately will be responsible for implementation of such an intervention. TRIAL
      REGISTRATION: United States Clinical Trails Register NCT 01494207.

PMID- 22625845
TI  - Brief daily exposures to Asian females reverses perceptual narrowing for Asian
      faces in Caucasian infants.
AB  - Perceptual narrowing in the visual, auditory, and multisensory domains has its
      developmental origins during infancy. The current study shows that experimentally
      induced experience can reverse the effects of perceptual narrowing on infants'
      visual recognition memory of other-race faces. Caucasian 8- to 10-month-olds who
      could not discriminate between novel and familiarized Asian faces at the
      beginning of testing were given brief daily experience with Asian female faces in
      the experimental condition and Caucasian female faces in the control condition.
      At the end of 3 weeks, only infants who received daily experience with Asian
      females showed above-chance recognition of novel Asian female and male faces.
      Furthermore, infants in the experimental condition showed greater efficiency in
      learning novel Asian females compared with infants in the control condition.
      Thus, visual experience with a novel stimulus category can reverse the effects of
      perceptual narrowing during infancy via improved stimulus recognition and
      encoding.

PMID- 22625846
TI  - Supervised hours requirements in graduated driver licensing: Effectiveness and
      parental awareness.
AB  - Most states require teens to complete a certain number of hours of supervised
      driving practice to obtain a license to drive unsupervised. Although widely
      implemented, the effect of requiring supervised practice is largely unknown.
      Using auto-regressive integrated moving average (ARIMA) interrupted time-series
      analysis, we found no change in fatal and injury crash involvement of 16-17-year
      old drivers in Minnesota following enactment of a 30h supervised driving
      requirement. To supplement and provide insight into these findings, we conducted
      telephone interviews with parents of newly licensed teenage drivers in five
      states with varying amounts of required supervised driving, including Minnesota.
      Interviews revealed awareness of supervised driving requirements was limited.
      Only a third of parents (32%) overall could correctly identify the number of
      hours their state required. In Minnesota only 15% of parents could identify the
      amount of supervised driving their teen was required to complete. Awareness of
      the number of hours required was substantially higher (55%) in Maryland. Unlike
      the other states, Maryland requires submission of a driving log detailing the
      hours of supervised driving. The findings suggest states need to develop more
      effective mechanisms to ensure parents are aware of supervised hours
      requirements.

PMID- 22625847
TI  - Decomposition of malonic anhydrides.
AB  - Malonic anhydrides decompose at or below room temperature, to form a ketene and
      carbon dioxide. Rate constants for the thermal decomposition of malonic,
      methylmalonic, and dimethylmalonic anhydrides were measured by NMR spectroscopy
      at various temperatures, and activation parameters were evaluated from the
      temperature dependence of the rate constants. Methylmalonic anhydride is the
      fastest, with the lowest DeltaH(?), and dimethylmalonic anhydride is the slowest.
      The nonlinear dependence on the number of methyl groups is discussed in terms of
      a concerted [2(s) + (2(s) + 2(s))] or [2(s) + 2(a)] cycloreversion that proceeds
      via a twisted transition-state structure, supported by computations.

PMID- 22625848
TI  - Novel biochemical manipulation of brain serotonin reveals a role of serotonin in
      the circadian rhythm of sleep-wake cycles.
AB  - Serotonin (5-HT) neurons have been implicated in the modulation of many
      physiological functions, including mood regulation, feeding, and sleep. Impaired
      or altered 5-HT neurotransmission appears to be involved in depression and
      anxiety symptoms, as well as in sleep disorders. To investigate brain 5-HT
      functions in sleep, we induced 5-HT deficiency through acute tryptophan depletion
      in rats by intraperitoneally injecting a tryptophan-degrading enzyme called
      tryptophan side chain oxidase I (TSOI). After the administration of TSOI (20
      units), plasma tryptophan levels selectively decreased to 1-2% of those of
      controls within 2 h, remained under 1% for 12-24 h, and then recovered between 72
      and 96 h. Following plasma tryptophan levels, brain 5-HT levels decreased to ~30%
      of the control level after 6 h, remained at this low level for 20-30 h, and
      returned to normal after 72 h. In contrast, brain norepinephreine and dopamine
      levels remained unchanged. After TSOI injection, the circadian rhythms of the
      sleep-wake cycle and locomotive activity were lost and broken into minute(s)
      ultradian alternations. The hourly slow-wave sleep (SWS) time significantly
      increased at night, but decreased during the day, whereas rapid eye movement
      sleep was significantly reduced during the day. However, daily total (cumulative)
      SWS time was retained at the normal level. As brain 5-HT levels gradually
      recovered 48 h after TSOI injection, the circadian rhythms of sleep-wake cycles
      and locomotive activity returned to normal. Our results suggest that 5-HT with a
      rapid turnover rate plays an important role in the circadian rhythm of sleep-wake
      cycles.

PMID- 22625850
TI  - Equisetum.

PMID- 22625849
TI  - Upstream stimulatory factor 1 activates GATA5 expression through an E-box motif.
AB  - Silencing of GATA5 gene expression as a result of promoter hypermethylation has
      been observed in lung, gastrointestinal and ovarian cancers. However, the
      regulation of GATA5 gene expression has been poorly understood. In the present
      study, we have demonstrated that an E (enhancer)-box in the GATA5 promoter (bp 
      118 to -113 in mice; bp -164 to -159 in humans) positively regulates GATA5
      transcription by binding USF1 (upstream stimulatory factor 1). Using site
      directed mutagenesis, EMSA (electrophoretic mobility-shift analysis) and affinity
      chromatography, we found that USF1 specifically binds to the E-box sequence (5'
      CACGTG-3'), but not to a mutated E-box. CpG methylation of this E-box
      significantly diminished its binding of transcription factors. Mutation of the E
      box within a GATA5 promoter fragment significantly decreased promoter activity in
      a luciferase reporter assay. Chromatin immunoprecipitation identified that USF1
      physiologically interacts with the GATA5 promoter E-box in mouse intestinal
      mucosa, which has the highest GATA5 gene expression in mouse. Co-transfection
      with a USF1 expression plasmid significantly increased GATA5 promoter-driven
      luciferase transcription. Furthermore, real-time and RT (reverse transcription)
      PCR analyses confirmed that overexpression of USF1 activates endogenous GATA5
      gene expression in human bronchial epithelial cells. The present study provides
      the first evidence that USF1 activates GATA5 gene expression through the E-box
      motif and suggests a potential mechanism (disruption of the E-box) by which GATA5
      promoter methylation reduces GATA5 expression in cancer.

PMID- 22625851
TI  - Sense of agency.

PMID- 22625852
TI  - Qualia.

PMID- 22625853
TI  - High temperature exposure increases plant cooling capacity.

PMID- 22625854
TI  - Developmental neurobiology: awakening the brain for the first time.
AB  - Imaging of the chicken embryo in the egg has revealed that the entire brain can
      be switched on for the first time earlier than expected by exposure to maternal
      vocalizations.

PMID- 22625855
TI  - RNA-directed DNA methylation: getting a grip on mechanism.
AB  - Small RNAs guide repressive chromatin modifications to regions of the genome
      containing transposons and repeats. An Arabidopsis genetic screen reveals that
      the guidance machinery includes a novel ATPase complex that could act as a
      dynamic molecular gripper.

PMID- 22625856
TI  - Animal culture: chimpanzee conformity?
AB  - Culture-like phenomena in wild animals have received much attention, but how good
      is the evidence and how similar are they to human culture? New data on
      chimpanzees suggest their culture may even have an element of conformity.

PMID- 22625857
TI  - DNA replication: Pif1 pulls the plug on stalled replication forks.
AB  - The conserved PIF helicase family appears to function in replication to ensure
      termination and passage through regions that slow or arrest replication fork
      movement. Findings in fission yeast extend evidence from budding yeast, and argue
      for universal mechanisms that ensure replication integrity.

PMID- 22625858
TI  - Biological clocks: who in this place set up a sundial?
AB  - How do circadian rhythms, alarm clocks and the light/dark cycle interact? The
      concept of social jetlag is informing our appreciation of the tensions and
      consequences of imposing an artificial temporal order upon our biology.

PMID- 22625859
TI  - Parallel selection: evolution's surprising predictability.
AB  - The mechanistic basis of how polygenic traits respond to selection is not well
      understood. New research provides compelling evidence for widespread parallel
      selection in independent mouse strains selected for extreme body weight.

PMID- 22625860
TI  - Pronuclear migration: no attachment? No union, but a futile cycle!
AB  - How do pronuclei migrate towards each other? The zebrafish futile cycle gene is
      shown to encode a maternally expressed membrane protein required for nuclear
      attachment and migration along the sperm aster.

PMID- 22625861
TI  - Cortical circuits: layer 6 is a gain changer.
AB  - Stimulation of excitatory cells in layer six of mouse visual cortex results in
      net inhibition of the spiking of neurons in upper cortical layers; this ascending
      intra-cortical drive provides a mechanism for gain modulation of sensory-evoked
      responses.

PMID- 22625863
TI  - Changes in centring and shaping ability using three  nickel-titanium
      instrumentation techniques  analysed by micro-computed tomography (MUCT).
AB  - AIM: To compare the centring ability and the shaping ability of ProTaper (PT)
      files used in reciprocating motion and PT and Twisted Files (TF) used in
      continuous rotary motion, and to compare the volume changes obtained with the
      different instrumentation techniques using micro-computed tomography. Methodology
      Sixty mesial canals of thirty mandibular molars were randomly assigned to three
      instrumentation techniques: group 1, canals prepared with the PT series (up to
      F2) (n = 20); group 2, canals prepared with the F2 PT in reciprocating motion (n
      = 20); group 3 canals prepared with the TF series (size 25) (n = 20). Teeth were
      scanned pre- and postoperatively using micro-computed tomography to measure
      volume and shaping changes, and the obtained results were statistically analysed
      using parametric tests. Results The increase in canal volume obtained with the
      three instrumentation techniques was not significantly different. Canals were
      transported mostly towards the mesial aspect in the apical- and mid-third of the
      roots, and towards the furcal aspect coronally. No difference in the
      transportation and centring ratio was found between the techniques. There was no
      significant difference between the times of instrumentation (TF: 62.5 +/- 5.4 s;
      PT: 60.6 +/- 3.9 s; and F2 PT file in reciprocating motion: 51.0 +/- 3.3 s).
      Conclusions ProTaper files used in reciprocating motion and PT and TF used in
      continuous rotary motion were capable of producing centred preparations with no
      substantial procedural errors.

PMID- 22625862
TI  - Golgi membrane dynamics and lipid metabolism.
AB  - The striking morphology of the Golgi complex has fascinated cell biologists since
      its discovery over 100 years ago. Yet, despite intense efforts to understand how
      membrane flow relates to Golgi form and function, this organelle continues to
      baffle cell biologists and biochemists alike. Fundamental questions regarding
      Golgi function, while hotly debated, remain unresolved. Historically, Golgi
      function has been described from a protein-centric point of view, but we now
      appreciate that conceptual frameworks for how lipid metabolism is integrated with
      Golgi biogenesis and function are essential for a mechanistic understanding of
      this fascinating organelle. It is from a lipid-centric perspective that we
      discuss the larger question of Golgi dynamics and membrane trafficking. We review
      the growing body of evidence for how lipid metabolism is integrally written into
      the engineering of the Golgi system and highlight questions for future study.

PMID- 22625864
TI  - Colloidal aggregation affects the efficacy of anticancer drugs in cell culture.
AB  - Many small molecules, including bioactive molecules and approved drugs,
      spontaneously form colloidal aggregates in aqueous solution at micromolar
      concentrations. Though it is widely accepted that aggregation leads to artifacts
      in screens for ligands of soluble proteins, the effects of colloid formation in
      cell-based assays have not been studied. Here, seven anticancer drugs and one
      diagnostic reagent were found to form colloids in both biochemical buffer and in
      cell culture media. In cell-based assays, the antiproliferative activities of
      three of the drugs were substantially reduced when in colloidal form as compared
      to monomeric form; a new formulation method ensured the presence of drug colloids
      versus drug monomers in solution. We also found that Evans Blue, a dye
      classically used to measure vascular permeability and to demonstrate the
      "enhanced permeability and retention (EPR) effect" in solid tumors, forms
      colloids that adsorb albumin, as opposed to older literature that suggested the
      reverse.

PMID- 22625865
TI  - Effect of oral contraceptive use on lipid profile in Korean women aged 35-55
      years.
AB  - BACKGROUND: Although oral contraceptives (OCs) are widely used, their effects on
      lipid profile need monitoring according to current usage in different
      populations. STUDY DESIGN: A cross-sectional study was conducted using data from
      1541 participants aged 35-55 years collected by the 2005-2009 Korea National
      Health and Nutrition Examination Surveys. OC use, demographic characteristics and
      dietary intake were obtained from the participants by questionnaire, and lipid
      levels were determined by analysis of blood samples. RESULTS: Longer duration of
      OC use was positively associated with increasing levels of high-density
      lipoprotein cholesterol (HDL-C) and decreasing levels of low-density lipoprotein
      cholesterol (LDL-C). After adjusting for demographic and dietary factors, the
      odds ratio (OR) of low HDL-C (<50 mg/dL) was significantly decreased in the
      longer-term (>12 months) OC users (OR=0.36, 95% confidence interval 0.24-0.52)
      compared with those who never used OCs. However, use of OCs was not associated
      with a risk of high total cholesterol (>= 240 mg/dL), high LDL-C (>= 130 mg/dL),
      high triglycerides (>= 150 mg/dL) or high ratio of triglycerides to HDL-C (>3.8).
      CONCLUSIONS: These data suggest that the use of OCs may reduce the risk of
      dyslipidemia, mainly due to the decreased risk of low HDL-C, in Korean women.

PMID- 22625866
TI  - A novel medical device for removal of intrauterine devices under direct vision.
AB  - BACKGROUND: Evaluation of the efficacy of a novel medical device for removal of
      retained intrauterine devices (IUDs) under direct vision without uterine
      distention is reported. CASES: The five cases presented used the novel medical
      device to remove the IUDs. One woman had an incarcerated IUD, two women had
      fractured IUDs and two women had IUDs with lost threads. All IUDs were removed
      completely with use of direct vision without uterine distention. CONCLUSIONS: The
      device is effective for the removal of incarceration IUDs under direct vision
      without uterine distention.

PMID- 22625867
TI  - Directly fused highly substituted naphthalenes via Pd-catalyzed dehydrogenative
      annulation of N,N-dimethylaminomethyl ferrocene using a redox process with a
      substrate.
AB  - N,N-Dimethylaminomethyl ferrocenium could be generated in situ and served as a
      terminal oxidant for Pd-catalyzed directly dehydrogenative annulations of N,N
      dimethylaminomethyl ferrocene and internal alkynes. This procedure utilized the
      redox activity of ferrocene and avoided adding an oxidant. A series of highly
      arylated naphthalenes functionalized by ferrocene were obtained in 53-81% yields.

PMID- 22625869
TI  - Breathlessness perception assessed by visual analogue scale and lung function in
      children with asthma: a real-life study.
AB  - BACKGROUND: In children with asthma, discrepancies between objective indicators
      of airway obstruction and symptom perception are often observed. Although visual
      analogue scale (VAS) has been proposed as a useful tool for assessing accurate
      symptom perception, previous studies conducted in children with asthma included
      only small cohorts. A study was therefore designed to investigate the usefulness
      of VAS in establishing a reliable relationship between breathlessness perception
      and lung function in a large cohort of children with clinical diagnosis of
      asthma. METHODS: A total of 703 children [470 boys and 233 girls, median age
      10.29 (8.33-12.58) yr] with asthma were included in this cross-sectional, real
      life study. Perception of breathlessness was assessed by using VAS, and lung
      volumes and expiratory flows were measured by spirometry. RESULTS: Most children
      had intermittent or mild persistent asthma (93.3%), and only 46 children had a
      significant bronchial obstruction defined by FEV(1) values <80% of predicted.
      Globally, VAS was significantly, even though weakly, related to lung function.
      Analyzing children with bronchial obstruction, a moderate relationship between
      both FEV(1) (r = 0.47) and FEF(25-75) (r = 0.42) and VAS was detected. A VAS
      value of 6 was found to be a reliable cutoff for discriminating children with
      bronchial obstruction (AUC 0.83 at ROC curve; OR 9.4). CONCLUSION: The present
      study demonstrates that VAS might be considered a useful tool to assess symptom
      perception, mainly in children with airflow limitation.

PMID- 22625868
TI  - Diagnostic imaging for spinal disorders in the elderly: a narrative review.
AB  - The high prevalence of neck and low back pain in the rapidly aging population is
      associated with significant increases in health care expenditure. While spinal
      imaging can be useful to identify less common causes of neck and back pain,
      overuse and misuse of imaging services has been widely reported. This narrative
      review aims to provide primary care providers with an overview of available
      imaging studies with associated potential benefits, adverse effects, and costs
      for the evaluation of neck and back pain disorders in the elderly population.
      While the prevalence of arthritis and degenerative disc disease increase with
      age, fracture, infection, and tumor remain uncommon. Prevalence of other
      conditions such as spinal stenosis and abdominal aortic aneurysm (AAA) also
      increase with age and demand special considerations. Radiography of the lumbar
      spine is not recommended for the early management of non-specific low back pain
      in adults under the age of 65. Aside from conventional radiography for suspected
      fracture or arthritis, magnetic resonance imaging (MRI) and computed tomography
      (CT) offer better characterization of most musculoskeletal diseases. If
      available, MRI is usually preferred over CT because it involves less radiation
      exposure and has better soft-tissue visualization. Use of subspecialty
      radiologists to interpret diagnostic imaging studies is recommended.

PMID- 22625870
TI  - The endothelium: influencing vascular smooth muscle in many ways.
AB  - The endothelium, although only a single layer of cells lining the vascular and
      lymphatic systems, contributes in multiple ways to vascular homeostasis.
      Subsequent to the 1980 report by Robert Furchgott and John Zawadzki, there has
      been a phenomenal increase in our knowledge concerning the signalling molecules
      and pathways that regulate endothelial - vascular smooth muscle communication. It
      is now recognised that the endothelium is not only an important source of nitric
      oxide (NO), but also numerous other signalling molecules, including the putative
      endothelium-derived hyperpolarizing factor (EDHF), prostacyclin (PGI(2)), and
      hydrogen peroxide (H(2)O(2)), which have both vasodilator and vasoconstrictor
      properties. In addition, the endothelium, either via transferred chemical
      mediators, such as NO and PGI(2), and (or) low-resistance electrical coupling
      through myoendothelial gap junctions, modulates flow-mediated vasodilatation as
      well as influencing mitogenic activity, platelet aggregation, and neutrophil
      adhesion. Disruption of endothelial function is an early indicator of the
      development of vascular disease, and thus an important area for further research
      and identification of potentially new therapeutic targets. This review focuses on
      the signalling pathways that regulate endothelial - vascular smooth muscle
      communication and the mechanisms that initiate endothelial dysfunction,
      particularly with respect to diabetic vascular disease.

PMID- 22625872
TI  - Nerve growth factor content is increased in the rectal mucosa of children with
      diarrhea-predominant irritable bowel syndrome.
AB  - BACKGROUND: The enteric nervous system is a complex network that includes, in the
      digestive mucosa, neuronal bodies and fibers interacting with the immune system
      and mucosal mast cells (MC). These interactions involve the secretion of
      messengers, such as the neurotrophin nerve growth factor (NGF), which influence
      colonic motility and sensitivity, both affected in irritable bowel syndrome
      (IBS). This study was designed to test the hypothesis that, in children with IBS,
      colonic mucosal innervation, NGF content, and MC infiltration are altered. We
      aimed to measure MC infiltration, number of neuronal bodies, distance from MC to
      nerve fibers, inflammation, and NGF content in rectal mucosa of pediatric
      patients with IBS as compared with controls. METHODS: Rectal biopsies from
      children (median age: 14 years) with diarrhea-predominant IBS (n = 11) and
      controls (n = 14) were studied. MC and neuronal mucosal structures were
      identified by tryptase, CD117 and PGP9.5 immunoreactivity. Inflammatory cells
      (neutrophils, eosinophils, and lymphocytes) were counted. NGF was quantified in
      situ by ELISA. KEY RESULTS: No mucosal inflammation was detected in IBS. MC
      infiltration and number of neuronal bodies were not significantly different
      between IBS and controls. The distance between MC and nerve fibers was not
      different in IBS compared with controls (5.2 +/- 0.3 vs 5.0 +/- 0.3 MUm). Number
      of MC in close proximity to nerve fibers (<5 MUm) was not different in the two
      groups. However, in IBS, NGF content was higher than controls (0.93 +/- 0.3 vs
      0.62 +/- 0.3 pg mg(-1) protein, P < 0.05) and significantly correlated with MC
      number. CONCLUSIONS & INFERENCES: Regardless of inflammation, NGF content is
      increased in rectal mucosa of diarrhea-predominant IBS children.

PMID- 22625871
TI  - Comparative metatranscriptomics reveals widespread community responses during
      phenanthrene degradation in soil.
AB  - Soil microbial community response to phenanthrene was evaluated by
      metatranscriptomics. A marked increase in transcripts involved in aromatic
      compound metabolism, respiration and stress responses, and concurrent decreases
      in virulence, carbohydrate, DNA metabolism and phosphorus metabolism transcripts
      was revealed. Phenanthrene addition led to a 1.8-fold to 33-fold increase in the
      abundance of dioxygenase, stress response and detoxification transcripts, whereas
      those of general metabolism were little affected. Heavy metal P-type ATPases and
      thioredoxin transcripts were more abundant in the phenanthrene-amended soil, and
      this is the first time these proteins have been associated with polycyclic
      aromatic hydrocarbon (PAH) stress in microorganisms. Annotation with custom
      databases constructed with bacterial or fungal PAH metabolism protein sequences
      showed that increases in PAH-degradatory gene expression occurred for all gene
      groups investigated. Taxonomic determination of mRNA transcripts showed
      widespread changes in the bacteria, archaea and fungi, and the actinobacteria
      were responsible for most of the de novo expression of transcripts associated
      with dioxygenases, stress response and detoxification genes. This is the first
      report of an experimental metatranscriptomic study detailing microbial community
      responses to a pollutant in soil, and offers information on novel in situ effects
      of PAHs on soil microbes that can be explored further.

PMID- 22625873
TI  - Mechanisms of interaction between Candida albicans and Streptococcus mutans: an
      experimental and mathematical modelling study.
AB  - OBJECTIVE: To evaluate the mechanisms of microbial interaction between the oral
      pathogens Candida albicans and Streptococcus mutans. MATERIALS AND METHODS:
      Growth kinetics for the two micro-organisms, cultured individually or together,
      were followed experimentally for 36 h. The different growth curves were analysed
      by means of mathematical modelling. RESULTS: Under the experimental conditions,
      S. mutans final concentration, when grown individually, was 5-times that of C.
      albicans. Contrarily, when both micro-organisms grew together, this ratio was
      inversed and C. albicans final concentration was even higher than that of S.
      mutans. When both micro-organisms share the niche, a model including linear
      competition among one another was best suited to reproduce the experimental
      observations. The results of this model show that the initial growth rates of
      both species are positively influenced by their mutual interaction. However, at
      longer incubation times, C. albicans prevents bacterial growth and achieves
      concentrations 4-times higher than when grown individually. CONCLUSIONS: The
      results suggest that C. albicans biofilm formation could be potentiated by the
      presence of S. mutans by two mechanisms: synergically at short times and by
      competition at longer periods.

PMID- 22625874
TI  - Differences in Danish children's diet quality on weekdays v. weekend days.
AB  - OBJECTIVE: To compare differences in children's diet quality on weekdays (Monday
      Thursday), Fridays and weekend days. DESIGN: A representative cross-sectional
      study in which participants completed a 7 d pre-coded food record. Mean intakes
      of energy, macronutrients and selected food items (g/10 MJ) as well as energy
      density were compared between weekdays, Fridays and weekend days for each gender
      in three age groups (4-6, 7-10 and 11-14 years) using Tobit analysis to account
      for zero intakes. SETTING: The Danish National Survey of Dietary Habits and
      Physical Activity 2003-2008. SUBJECTS: Children (n 784; 49.9 % boys) aged 4-14
      years. RESULTS: For both genders in all age groups (P < 0.05), energy intake was
      higher during weekends than on weekdays, and intakes of sugar-sweetened beverages
      and white bread were higher, whereas intake of rye bread was lower. This
      contributed to a higher percentage of energy from added sugars, a lower fibre
      content and a higher energy density on weekend days v. weekdays. In children aged
      4-6 and 7-10 years, the diet on weekend days was also characterized by higher
      intakes of sweets and chocolate and lower intakes of fruit and vegetables.
      Overall, the diet on Fridays appeared as a mix of the diets on weekdays and
      weekend days. CONCLUSIONS: Significant differences and distinct characteristic
      patterns were found in children's diet quality during weekdays, Fridays and
      weekend days. The present study suggests that in prevention of childhood
      overweight and obesity, more attention should be paid to the higher energy
      intake, especially from sugar-rich foods and beverages, on Fridays and weekend
      days.

PMID- 22625875
TI  - Thinning and functionalization of few-layer graphene sheets by CF4 plasma
      treatment.
AB  - Structural changes of few-layer graphene sheets induced by CF4 plasma treatment
      are studied by optical microscopy and Raman spectroscopy, together with
      theoretical simulation. Experimental results suggest a thickness reduction of few
      layer graphene sheets subjected to prolonged CF4 plasma treatment while plasma
      treatment with short time only leads to fluorine functionalization on the surface
      layer by formation of covalent bonds. Raman spectra reveal an increase in
      disorder by physical disruption of the graphene lattice as well as
      functionalization during the plasma treatment. The F/CF3 adsorption and the
      lattice distortion produced are proved by theoretical simulation using density
      functional theory, which also predicts p-type doping and Dirac cone splitting in
      CF4 plasma-treated graphene sheets that may have potential in future graphene
      based micro/nanodevices. PACS: 81.05.ue; 73.22.Pr; 52.40.Hf.

PMID- 22625876
TI  - Effect of moisture, lipids, and select amino acid blocking agents on the
      formation and stability of metastable radicals in powdered soy proteins.
AB  - Incremental increases in the moisture content of powdered soy protein products
      from 4.4% to 13.4% produced an inverse effect on the ability of soy proteins to
      maintain metastable free radicals. The corresponding reduction in electron
      paramagnetic resonance signal was not due to dielectric loss in the range of
      moisture contents examined. Subsequent evaluations of various treatments were
      conducted after drying soy proteins with molecular sieve to a water activity
      below 0.085 in order to minimize the influence from variations in moisture.
      Isolated soy protein (ISP) samples, prepared with "defatted flour" that had been
      further extracted with chloroform/methanol (2: 1), had a 96% reduction in total
      lipids compared to the control ISP samples. The initial rate of radical
      accumulation in the "reduced-lipid" ISP for the first 3 wk was not significantly
      different from the initial rate of radical increases in the control ISP. After 3
      wk, radical accumulation in the "reduced-lipid" ISP continued to increase, but at
      a rate that was less than the control. These findings indicate that the initial
      reactions contributing to the formation of metastable radicals in the powdered
      ISP are not strongly dependent on associated lipids. Blocking sulfhydryl groups
      during ISP preparation with N-ethylmaleimide did not significantly slow the rate
      of radical accumulation compared to the control ISP. Blocking arginine residues
      in ISP samples with phenylglyoxal caused an increased rate of radical
      accumulation for the first 4 wk. PRACTICAL APPLICATION: Levels of metastable
      radicals in powdered soy protein products typically range from 10 to 100 times
      greater than the free radicals in other food protein sources. This current
      research examines various compositional and treatment parameters that might be
      used to minimize the content of free radicals in foods containing soy proteins.

PMID- 22625877
TI  - Impact of the CYP2C8 *3 polymorphism on the drug-drug interaction between
      gemfibrozil and pioglitazone.
AB  - AIM: The objective of this study was to determine the extent to which the
      CYP2C8*3 allele influences pharmacokinetic variability in the drug-drug
      interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8
      substrate). METHODS: In this randomized, two phase crossover study, 30 healthy
      Caucasian subjects were enrolled based on CYP2C8*3 genotype (n = 15, CYP2C8*1/*1;
      n = 15, CYP2C8*3 carriers). Subjects received a single 15 mg dose of pioglitazone
      or gemfibrozil 600 mg every 12 h for 4 days with a single 15 mg dose of
      pioglitazone administered on the morning of day 3. A 48 h pharmacokinetic study
      followed each pioglitazone dose and the study phases were separated by a 14 day
      washout period. RESULTS: Gemfibrozil significantly increased mean pioglitazone
      AUC(0,infinity) by 4.3-fold (P < 0.001) and there was interindividual variability
      in the magnitude of this interaction (range, 1.8- to 12.1-fold). When
      pioglitazone was administered alone, the mean AUC(0,infinity) was 29.7% lower (P
      = 0.01) in CYP2C8*3 carriers compared with CYP2C8*1 homozygotes. The relative
      change in pioglitazone plasma exposure following gemfibrozil administration was
      significantly influenced by CYP2C8 genotype. Specifically, CYP2C8*3 carriers had
      a 5.2-fold mean increase in pioglitazone AUC(0,infinity) compared with a 3.3-fold
      mean increase in CYP2C8*1 homozygotes (P = 0.02). CONCLUSION: CYP2C8*3 is
      associated with decreased pioglitazone plasma exposure in vivo and significantly
      influences the pharmacokinetic magnitude of the gemfibrozil-pioglitazone drug
      drug interaction. Additional studies are needed to evaluate the impact of CYP2C8
      genetics on the pharmacokinetics of other CYP2C8-mediated drug-drug interactions.

PMID- 22625878
TI  - Nutrition education intervention for dependent patients: protocol of a randomized
      controlled trial.
AB  - BACKGROUND: Malnutrition in dependent patients has a high prevalence and can
      influence the prognosis associated with diverse pathologic processes, decrease
      quality of life, and increase morbidity-mortality and hospital admissions.The aim
      of the study is to assess the effect of an educational intervention for
      caregivers on the nutritional status of dependent patients at risk of
      malnutrition. METHODS/DESIGN: Intervention study with control group, randomly
      allocated, of 200 patients of the Home Care Program carried out in 8 Primary Care
      Centers (Spain). These patients are dependent and at risk of malnutrition, older
      than 65, and have caregivers. The socioeconomic and educational characteristics
      of the patient and the caregiver are recorded. On a schedule of 0-6-12 months,
      patients are evaluated as follows: Mini Nutritional Assessment (MNA), food
      intake, dentures, degree of dependency (Barthel test), cognitive state (Pfeiffer
      test), mood status (Yesavage test), and anthropometric and serum parameters of
      nutritional status: albumin, prealbumin, transferrin, haemoglobin, lymphocyte
      count, iron, and ferritin.Prior to the intervention, the educational procedure
      and the design of educational material are standardized among nurses. The nurses
      conduct an initial session for caregivers and then monitor the education impact
      at home every month (4 visits) up to 6 months. The North American Nursing
      Diagnosis Association (NANDA) methodology will be used. The investigators will
      study the effect of the intervention with caregivers on the patient's nutritional
      status using the MNA test, diet, anthropometry, and biochemical
      parameters.Bivariate normal test statistics and multivariate models will be
      created to adjust the effect of the intervention.The SPSS/PC program will be used
      for statistical analysis. DISCUSSION: The nutritional status of dependent
      patients has been little studied. This study allows us to know nutritional risk
      from different points of view: diet, anthropometry and biochemistry in dependent
      patients at nutritional risk and to assess the effect of a nutritional education
      intervention. The design with random allocation, inclusion of all patients,
      validated methods, caregivers' education and standardization between nurses
      allows us to obtain valuable information about nutritional status and prevention.
      TRIAL REGISTRATION NUMBER: Clinical Trial Registration-URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01360775.

PMID- 22625994
TI  - Structure-activity studies on the spiroketal moiety of a simplified analogue of
      debromoaplysiatoxin with antiproliferative activity.
AB  - Aplog-1, a simplified analogue of tumor-promoting debromoaplysiatoxin, is
      antiproliferative but not tumor-promoting. Our recent study has suggested that
      local hydrophobicity around the spiroketal moiety is a crucial determinant for
      antiproliferative activity. To further clarify the structural features relevant
      to the activity, we synthesized two methyl derivatives of aplog-1, where a methyl
      group was installed at position 4 or 10 of the spiroketal moiety. 10-Methyl-aplog
      1 (5) bound to the C1B domains of novel PKCs (delta, eta, and theta) with
      subnanomolar K(i) values, approximately 10-20 times stronger than aplog-1, and
      markedly inhibited the growth of many human cancer cell lines, while 4-methyl
      aplog-1 (4) had levels of activity similar to those of aplog-1. Interestingly, 5
      showed little tumor-promoting activity unlike the tumor promoter
      debromoaplysiatoxin. These results suggest that 5 is a potent PKC ligand without
      tumor-promoting activity and could be a therapeutic lead for the treatment of
      cancer, like bryostatins.

PMID- 22625995
TI  - The consequences of foreclosure for depressive symptomatology.
AB  - PURPOSE: We tested whether experiencing the stressful event of a home mortgage
      foreclosure was associated with depressive symptomatology. METHODS: Data derive
      from a cohort study of 662 new mothers in the Life-course Influences on Fetal
      Environment (LIFE) Study. Eligibility included black/African-American mothers,
      ages 18 to 45 years, who had just given birth to a singleton baby. Mothers
      enrolled June 2009 to December 2010 were interviewed immediately after giving
      birth. Our outcome measure was depressive symptoms based on the Center for
      Epidemiologic Studies-Depression Scale, dichotomized to measure severe depressive
      symptomatology during the week prior to the interview. RESULTS: A total of 8% of
      the sample experienced foreclosure in the past 2 years. Covariate-adjusted
      Poisson regression models showed that women experiencing a recent foreclosure had
      1.76 times greater risk for severe depressive symptoms during the week prior to
      birth compared to women not experiencing foreclosure (95% confidence interval
      1.25-2.47, p = .001); foreclosure was also associated with higher excess absolute
      risk for depressive symptoms (adjusted risk difference 0.173, 95% confidence
      interval 0.044-0.301, p = .008). CONCLUSIONS: Women who have recently experienced
      foreclosure are at risk for severe depressive symptoms. The mental health needs
      of pregnant women experiencing foreclosure or other housing stressors should be
      considered in clinical practice.

PMID- 22625996
TI  - Differential impact of risk factors for women and men on the risk of major
      depressive disorder.
AB  - PURPOSE: Our aim is to examine which risk factors have a greater impact in women
      than in men on the risk of major depressive disorder (MDD) and whether factors
      differ between a possible recurrent MDD and a first onset of MDD. METHODS:
      Prospective cohort study of general practice attendees in seven countries, who
      were followed up at 6 and 12 months (predictD). Absolute risk differences
      (interaction contrast) across sex for onset of DSM-IV MDD after 6 or 12 months of
      follow-up were estimated for 35 risk factors from 7101 participants without MDD
      at baseline. RESULTS: A total of 599 participants (80% female) had an onset of
      MDD at 6 or 12 months. Most risk factors had a greater impact in women than in
      men on the risk of MDD and were not restricted to a specific class of risk
      factors. After we stratified for a history of depressive symptoms, we found that
      the impact of risk factors across sex was generally stronger on possible
      recurrent MDD than on a first onset of MDD. CONCLUSIONS: Our findings may partly
      account for the observed difference in incidence of MDD between men and women.

PMID- 22625997
TI  - Problems with the collection and interpretation of Asian-American health data:
      omission, aggregation, and extrapolation.
AB  - Asian-American citizens are the fastest growing racial/ethnic group in the United
      States. Nevertheless, data on Asian American health are scarce, and many health
      disparities for this population remain unknown. Much of our knowledge of Asian
      American health has been determined by studies in which investigators have either
      grouped Asian-American subjects together or examined one subgroup alone (e.g.,
      Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese). National health
      surveys that collect information on Asian-American race/ethnicity frequently omit
      this population in research reports. When national health data are reported for
      Asian-American subjects, it is often reported for the aggregated group. This
      aggregation may mask differences between Asian-American subgroups. When health
      data are reported by Asian American subgroup, it is generally reported for one
      subgroup alone. In the Ni-Hon-San study, investigators examined cardiovascular
      disease in Japanese men living in Japan (Nippon; Ni), Honolulu, Hawaii (Hon), and
      San Francisco, CA (San). The findings from this study are often incorrectly
      extrapolated to other Asian-American subgroups. Recommendations to correct the
      errors associated with omission, aggregation, and extrapolation include:
      oversampling of Asian Americans, collection and reporting of race/ethnicity data
      by Asian-American subgroup, and acknowledgement of significant heterogeneity
      among Asian American subgroups when interpreting data.

PMID- 22625998
TI  - Does the African-American-white mortality gap persist after playing professional
      basketball? A 59-year historical cohort study.
AB  - PURPOSE: The African-American-white mortality gap for males in the United States
      is 6 years in favor of whites. Participation in professional sport may moderate
      this ethnic disparity. The historical cohort of professional basketball players,
      with nearly equal numbers of African-American and white players, can provide a
      natural experiment that may control for the classic confounders of income,
      education, socioeconomic status (SES), and physical factors related to mortality.
      The objectives of this study are to assess mortality and calculate survival for
      the overall study population and within ethnicity. METHODS: Data were combined
      from several publicly available sources. The cohort was analyzed to compare
      longevity among all players, and for players stratified by ethnicity, with the
      general U.S. population. RESULTS: The final dataset included 3366 individuals, of
      whom 56.0% were African American. Results suggest white players live 18 months
      longer than their African-American colleagues. African-American players gained 9
      years on their respective referent and live longer than white men in the general
      public. After controlling for covariates, we found that African-American players
      have a 75% increased risk of death compared with white players, a statistically
      significant gap (p < .0001, 95% confidence interval 1.41-2.44). CONCLUSIONS: The
      African-American-white mortality gap for males is largely ameliorated (1.5 years
      vs. 6.1 years) in professional basketball but still persists.

PMID- 22625999
TI  - How do we more effectively move epidemiology into policy action?
AB  - A major focus of the American College of Epidemiology's Policy Committee has been
      to review the translation of epidemiologic evidence into policy by developing
      case studies. This article summarizes crosscutting policy process lessons across
      the eight cases developed to date through two workshops held in 2009 and 2011. A
      framework for evidence-based public health policy has emerged to suggest that
      process, content, and outcomes are all needed to help move policy forward. The
      most readily and apparent contributions from epidemiologists are towards content
      and outcomes activities, and although this is apparent in all of the case studies
      presented, much of the 2011 workshop discussion focused on six process issues.
      Policy and process issues are not well incorporated into current epidemiologic
      training, and controversy remains over the role of the epidemiologist as an
      advocate for policy changes. As these case studies show, epidemiologic evidence
      impacts policy to address emerging public health problems, yet few
      epidemiologists are formally trained in the domains to support policy
      development. As we continue to learn from current policy efforts, we encourage
      the incorporation of these case studies and the emerging experience within
      epidemiologic training programs.

PMID- 22626000
TI  - Population-wide sodium reduction: the bumpy road from evidence to policy.
AB  - Elevated blood pressure is a highly prevalent condition that is etiologically
      related to coronary heart disease and stroke, two of the leading causes of
      morbidity and mortality throughout the world. Excess salt (sodium chloride)
      intake is a major determinant of elevated blood pressure. In this article, we
      discuss the scientific rationale for population-wide salt reduction, the types
      and strength of available evidence, policy-making on dietary salt intake in the
      United States and other countries, and the role and impact of key stakeholders.
      We highlight a number of lessons learned, many of which are germane to policy
      development in other domains.

PMID- 22626002
TI  - Cancer screening: the journey from epidemiology to policy.
AB  - PURPOSE: Cancer screening procedures have brought great benefit to the public's
      health. However, the science of cancer screening and the evidence arising from
      research in this field as it is applied to policy is complex and has been
      difficult to communicate, especially on the national stage. We explore how
      epidemiologists have contributed to this evidence base and to its translation
      into policy. METHODS: Our essay focuses on breast and lung cancer screening to
      identify commonalities of experience by epidemiologists across two different
      cancer sites and describe how epidemiologists interact with evolving scientific
      and policy environments. RESULTS: We describe the roles and challenges that
      epidemiologists encounter according to the maturity of the data, stakeholders,
      and the related political context. We also explore the unique position of cancer
      screening as influenced by the legislative landscape where, due to recent
      healthcare reform, cancer screening research plays directly into national policy.
      CONCLUSIONS: In the complex landscape for cancer screening policy,
      epidemiologists can increase their impact by learning from past experiences,
      being well prepared and communicating effectively.

PMID- 22626001
TI  - The emerging HIV epidemic on the Mexico-U.S. border: an international case study
      characterizing the role of epidemiology in surveillance and response.
AB  - PURPOSE: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome
      surveillance data are critical for monitoring epidemic trends, but they can mask
      dynamic subepidemics, especially in vulnerable populations that underuse HIV
      testing. In this case study, we describe community-based epidemiologic data among
      injection drug users (IDUs) and female sex workers (FSWs) in two northern Mexico
      U.S. border states that identified an emerging HIV epidemic and generated a
      policy response. METHODS: We draw from quantitative and qualitative cross
      sectional and prospective epidemiologic studies and behavioral intervention
      studies among IDUs and FSWs in Tijuana, Baja California, and Ciudad Juarez,
      Chihuahua. RESULTS: The recognition that the HIV epidemic on Mexico's northern
      border was already well established in subgroups in whom it had been presumed to
      be insignificant was met with calls for action and enhanced prevention efforts
      from researchers, nongovernmental organizations, and policy makers. CONCLUSIONS:
      Successful policies and program outcomes included expansion of needle-exchange
      programs, a nationwide mobile HIV prevention program targeting marginalized
      populations, a successful funding bid from the Global Fund for HIV, TB, and
      Malaria to scale up targeted HIV-prevention programs, and the establishment of bi
      national training programs on prevention of HIV and substance use. We discuss how
      epidemiologic data informed HIV prevention policies and suggest how other
      countries may learn from Mexico's experience.

PMID- 22626003
TI  - Epidemiology, policy, and racial/ethnic minority health disparities.
AB  - PURPOSE: Epidemiologists have long contributed to policy efforts to address
      health disparities. Three examples illustrate how epidemiologists have addressed
      health disparities in the United States and abroad through a "social determinants
      of health" lens. METHODS: To identify examples of how epidemiologic research has
      been applied to reduce health disparities, we queried epidemiologists engaged in
      disparities research in the United States, Canada, and New Zealand, and drew upon
      the scientific literature. RESULTS: Resulting examples covered a wide range of
      topic areas. Three areas selected for their contributions to policy were: (1)
      epidemiology's role in definition and measurement, (2) the study of housing and
      asthma, and (3) the study of food policy strategies to reduce health disparities.
      Although epidemiologic research has done much to define and quantify health
      inequalities, it has generally been less successful at producing evidence that
      would identify targets for health equity intervention. Epidemiologists have a
      role to play in measurement and basic surveillance, etiologic research,
      intervention research, and evaluation research. However, our training and funding
      sources generally place greatest emphasis on surveillance and etiologic research.
      CONCLUSIONS: The complexity of health disparities requires better training for
      epidemiologists to effectively work in multidisciplinary teams. Together we can
      evaluate contextual and multilevel contributions to disease and study
      intervention programs to gain better insights into evidenced-based health equity
      strategies.

PMID- 22626004
TI  - Mechanically untying a protein slipknot: multiple pathways revealed by force
      spectroscopy and steered molecular dynamics simulations.
AB  - Protein structure is highly diverse when considering a wide range of protein
      types, helping to give rise to the multitude of functions that proteins perform.
      In particular, certain proteins are known to adopt a knotted or slipknotted fold.
      How such proteins undergo mechanical unfolding was investigated utilizing a
      combination of single molecule atomic force microscopy (AFM), protein
      engineering, and steered molecular dynamics (SMD) simulations to show the
      mechanical unfolding mechanism of the slipknotted protein AFV3-109. Our results
      reveal that the mechanical unfolding of AFV3-109 can proceed via multiple
      parallel unfolding pathways that all cause the protein slipknot to untie and the
      polypeptide chain to completely extend. These distinct unfolding pathways proceed
      via either a two- or three-state unfolding process involving the formation of a
      well-defined, stable intermediate state. SMD simulations predict the same contour
      length increments for different unfolding pathways as single molecule AFM
      results, thus providing a plausible molecular mechanism for the mechanical
      unfolding of AFV3-109. These SMD simulations also reveal that two-state unfolding
      is initiated from both the N- and C-termini, while three-state unfolding is
      initiated only from the C-terminus. In both pathways, the protein slipknot was
      untied during unfolding, and no tightened slipknot conformation was observed.
      Detailed analysis revealed that interactions between key structural elements lock
      the knotting loop in place, preventing it from shrinking and the formation of a
      tightened slipknot conformation. Our results demonstrate the bifurcation of the
      mechanical unfolding pathway of AFV3-109 and point to the generality of a kinetic
      partitioning mechanism for protein folding/unfolding.

PMID- 22626005
TI  - Pediatric and neonatal extracorporeal life support technology component
      utilization: are US clinicians implementing new technology?
AB  - The objective of this investigation is to describe recent changes made in
      extracorporeal life support (ECLS) technology in the US Postal survey to
      directors and coordinators of all 125 US ECLS centers identified by
      Extracorporeal Life Support Organization as of November 2010, with follow-up of
      nonrespondents. Spearman coefficients were used to correlate the method of
      updating knowledge of ECLS technology with the likelihood of changing technology,
      and to correlate decision-making hierarchy with the likelihood of changing
      equipment. The response rate was 75% representing 34 states, and the majority of
      respondents were ECLS coordinators (56.6%). Respiratory diagnosis is the
      predominant indication for ECLS at any age. Over 40% of centers are using a
      hollow-fiber oxygenator for neonates and 80% of pediatric patients. Roller pumps
      are used in 70% of neonatal and pediatric ECLS. Forty-two percent of centers
      changed the oxygenator type within the past 3 years, while 30% changed both the
      oxygenator and pump. Less than 10% of centers reported problems with either
      oxygenator or pump in both neonates and pediatric ECLS. Forty-six percent of
      respondents that changed oxygenators cited that the primary reason for changing
      was "clinical preference/experience," while the other half was split between "FDA
      approval" and "Research results." In 40% of centers, a multidisciplinary group
      made decisions on changing technology. This survey indicates that over one-half
      of ECLS centers implemented new technology within the past 3 years. Knowledge of
      ECLS technology and safe operation of ECLS circuit components is essential in
      preventing some of the mechanical complications.

PMID- 22626006
TI  - Responses to two-dimensional shapes in the macaque anterior intraparietal area.
AB  - Neurons in the macaque dorsal visual stream respond to the visual presentation of
      objects in the context of a grasping task and to three-dimensional (3D) surfaces
      defined by binocular disparity, but little is known about the neural
      representation of two-dimensional (2D) shape in the dorsal stream. We recorded
      the activity of single neurons in the macaque anterior intraparietal area (AIP),
      which is known to be crucial for grasping, during the presentation of images of
      objects and silhouette, outline and line-drawing versions of these images
      (contour stimuli). The vast majority of AIP neurons responding selectively to 2D
      images were also selective for at least one of the contour stimuli with the same
      boundary shape, suggesting that the boundary is sufficient for the image
      selectivity of most AIP neurons. Furthermore, a subset of these neurons with
      foveal receptive fields generally preserved the shape preference across
      positions, whereas for more than half of the AIP population the center of the
      receptive field was at a parafoveal location with less tolerance to changes in
      stimulus position. AIP neurons frequently exhibited shape selectivity across
      different stimulus sizes. These results demonstrate that AIP neurons encode not
      only 3D but also 2D shape features.

PMID- 22626007
TI  - Rapid compensation of visual search strategy in patients with chronic visual
      field defects.
AB  - INTRODUCTION: The aim of this study was to test the effect and specificity of a
      novel, compensatory eye movement training therapy designed to improve visual
      search performance in patients with homonymous visual field defects. METHODS:
      Seven patients with chronic homonymous visual field defects and six healthy
      control subjects were tested. All subjects completed the single training period
      (300 trials). Subjects were assessed on three different saccadic tasks (a visual
      search task, a rapid scanning task and a reading task) which were evaluated at
      three time points on the same day: two before and one after the training period.
      The computer-based training consisted of a novel ramp-step search paradigm that
      required subjects to pursue a stimulus (ramp phase) and then saccade to find its
      location when it suddenly jumped (step phase). RESULTS: Pre-therapy we confirmed
      that patients differed from controls on the visual search task. Post-training we
      demonstrated a clear improvement in terms of reaction time required to complete
      the visual search. This effect was confined to: (1) the patient group only; (2)
      targets presented to the blind visual field of the patients only; (3) the visual
      search task only and not the rapid scanning or reading task. CONCLUSION: These
      results demonstrate that rapid, compensatory changes can occur in patients with
      visual field defects that impact on their ability to carry out efficient visual
      search. We plan to translate this therapy, along with appropriate testing
      materials, in a free-to-use, internet-based application based on this
      intervention.

PMID- 22626008
TI  - Organocatalyzed enantioselective formal [4 + 2] cycloaddition of 2,3
      disubstituted indole and methyl vinyl ketone.
AB  - A formal [4 + 2] cycloaddition of 2,3-disubstituted indoles with vinyl methyl
      ketone was realized in the presence of a catalytic amount of quinine-derived
      primary amine and pentafluorobenzoic acid. This method provides bridged-ring
      indoline scaffolds containing two quaternary carbon centers with excellent yields
      and enantioselectivity (up to 98% yield and 98% ee).

PMID- 22626010
TI  - Low-oxidation state indium-catalyzed C-C bond formation.
AB  - The development of innovative metal catalysis for selective bond formation is an
      important task in organic chemistry. The group 13 metal indium is appealing for
      catalysis because indium-based reagents are minimally toxic, selective, and
      tolerant toward various functional groups. Among elements in this group, the most
      stable oxidation state is typically +3, but in molecules with larger group 13
      atoms, the chemistry of the +1 oxidation state is also important. The use of
      indium(III) compounds in organic synthesis has been well-established as Lewis
      acid catalysts including asymmetric versions thereof. In contrast, only sporadic
      examples of the use of indium(I) as a stoichiometric reagent have been reported:
      to the best of our knowledge, our investigations represent the first synthetic
      method that uses a catalytic amount of indium(I).  Depending on the nature of the
      ligand or the counteranion to which it is coordinated, indium(I) can act as both
      a Lewis acid and a Lewis base because it has both vacant p orbitals and a lone
      pair of electrons. This potential ambiphilicity may offer unique reactivity and
      unusual selectivity in synthesis and may have significant implications for
      catalysis, particularly for dual catalytic processes. We envisioned that
      indium(I) could be employed as a metallic Lewis base catalyst to activate Lewis
      acidic boron-based pronucleophiles for selective bond formation with suitable
      electrophiles. Alternatively, indium(I) could serve as an ambiphilic catalyst
      that activates both reagents at a single center.  In this Account, we describe
      the development of low-oxidation state indium catalysts for carbon-carbon bond
      formation between boron-based pronucleophiles and various electrophiles. We
      discovered that indium(I) iodide was an excellent catalyst for alpha-selective
      allylations of C(sp(2)) electrophiles such as ketones and hydrazones. Using a
      combination of this low-oxidation state indium compound and a chiral semicorrin
      ligand, we developed catalytic highly enantioselective allylation, crotylation,
      and alpha-chloroallylation reactions of hydrazones. These transformations
      proceeded with rare constitutional selectivities and remarkable
      diastereoselectivities. Furthermore, indium(I) triflate served as the most
      effective catalyst for allylations and propargylations of C(sp(3)) electrophiles
      such as O,O-acetals, N,O-aminals, and ethers, and we applied this methodology to
      carbohydrate chemistry. In addition, a catalyst system composed of indium(I)
      chloride and a chiral silver BINOL-phosphate facilitated the highly
      enantioselective allylation and allenylation of N,O-aminals. Overall, these
      discoveries demonstrate the versatility, efficiency, and sensitivity of low
      oxidation state indium catalysts in organic synthesis.

PMID- 22626009
TI  - Biomarkers of coagulation, inflammation, and angiogenesis are independently
      associated with preeclampsia.
AB  - PROBLEM: Although preeclampsia has been associated with inflammation,
      coagulation, and angiogenesis, their correlation and relative contribution are
      unknown. METHOD OF STUDY: About 114 women with preeclampsia, 31 with early onset
      (EOP) and 83 with late onset preeclampsia (LOP), and 100 normal pregnant controls
      were included. A broad panel of 32 biomarkers reflecting coagulation,
      inflammation, and angiogenesis was analyzed. RESULTS: Preeclampsia was associated
      with decreased antithrombin, IL-4 and placental growth factor levels and with
      increased C3a, pentraxin-3, and sFlt-1 levels, with more marked differences in
      the EOP group. The Th1-associated chemokines CXCL10 and CXCL11 were significantly
      higher in the preeclampsia and EOP group than in controls, respectively. No
      correlations between the biomarkers were found in preeclampsia. Multivariate
      logistic regression tests confirmed the results. CONCLUSIONS: Cytokines,
      chemokines and complement activation seem to be part of a Th1-like inflammatory
      reaction in preeclampsia, most pronounced in EOP, where chemokines may be more
      useful than cytokines as biomarkers. Biomarkers were not correlated suggesting
      partly independent or in time separated mechanisms.

PMID- 22626011
TI  - Endothelial calcium-activated potassium channels as therapeutic targets to
      enhance availability of nitric oxide.
AB  - The vascular endothelium plays a critical role in vascular health by controlling
      arterial diameter, regulating local cell growth, and protecting blood vessels
      from the deleterious consequences of platelet aggregation and activation of
      inflammatory responses. Circulating chemical mediators and physical forces act
      directly on the endothelium to release diffusible relaxing factors, such as
      nitric oxide (NO), and to elicit hyperpolarization of the endothelial cell
      membrane potential, which can spread to the surrounding smooth muscle cells via
      gap junctions. Endothelial hyperpolarization, mediated by activation of calcium
      activated potassium (K(Ca)) channels, has generally been regarded as a distinct
      pathway for smooth muscle relaxation. However, recent evidence supports a role
      for endothelial K(Ca) channels in production of endothelium-derived NO, and
      indicates that pharmacological activation of these channels can enhance NO
      mediated responses. In this review we summarize the current data on the
      functional role of endothelial K(Ca) channels in regulating NO-mediated changes
      in arterial diameter and NO production, and explore the tempting possibility that
      these channels may represent a novel avenue for therapeutic intervention in
      conditions associated with reduced NO availability such as hypertension,
      hypercholesterolemia, smoking, and diabetes mellitus.

PMID- 22626012
TI  - Laryngeal leishmaniasis as a differential diagnosis of glottic leukoplakia.

PMID- 22626013
TI  - Mounier-Kuhn syndrome.

PMID- 22626014
TI  - Eye pain after blunt ocular trauma. Traumatic mydriasis with hyphema.

PMID- 22626015
TI  - Immediate and delayed traumatic intracranial hemorrhage in patients with head
      trauma and preinjury warfarin or clopidogrel use.
AB  - STUDY OBJECTIVE: Patients receiving warfarin or clopidogrel are considered at
      increased risk for traumatic intracranial hemorrhage after blunt head trauma. The
      prevalence of immediate traumatic intracranial hemorrhage and the cumulative
      incidence of delayed traumatic intracranial hemorrhage in these patients,
      however, are unknown. The objective of this study is to address these gaps in
      knowledge. METHODS: A prospective, observational study at 2 trauma centers and 4
      community hospitals enrolled emergency department (ED) patients with blunt head
      trauma and preinjury warfarin or clopidogrel use from April 2009 through January
      2011. Patients were followed for 2 weeks. The prevalence of immediate traumatic
      intracranial hemorrhage and the cumulative incidence of delayed traumatic
      intracranial hemorrhage were calculated from patients who received initial
      cranial computed tomography (CT) in the ED. Delayed traumatic intracranial
      hemorrhage was defined as traumatic intracranial hemorrhage within 2 weeks after
      an initially normal CT scan result and in the absence of repeated head trauma.
      RESULTS: A total of 1,064 patients were enrolled (768 warfarin patients [72.2%]
      and 296 clopidogrel patients [27.8%]). There were 364 patients (34.2%) from Level
      I or II trauma centers and 700 patients (65.8%) from community hospitals. One
      thousand patients received a cranial CT scan in the ED. Both warfarin and
      clopidogrel groups had similar demographic and clinical characteristics, although
      concomitant aspirin use was more prevalent among patients receiving clopidogrel.
      The prevalence of immediate traumatic intracranial hemorrhage was higher in
      patients receiving clopidogrel (33/276, 12.0%; 95% confidence interval [CI] 8.4%
      to 16.4%) than patients receiving warfarin (37/724, 5.1%; 95% CI 3.6% to 7.0%),
      relative risk 2.31 (95% CI 1.48 to 3.63). Delayed traumatic intracranial
      hemorrhage was identified in 4 of 687 (0.6%; 95% CI 0.2% to 1.5%) patients
      receiving warfarin and 0 of 243 (0%; 95% CI 0% to 1.5%) patients receiving
      clopidogrel. CONCLUSION: Although there may be unmeasured confounders that limit
      intergroup comparison, patients receiving clopidogrel have a significantly higher
      prevalence of immediate traumatic intracranial hemorrhage compared with patients
      receiving warfarin. Delayed traumatic intracranial hemorrhage is rare and
      occurred only in patients receiving warfarin. Discharging patients receiving
      anticoagulant or antiplatelet medications from the ED after a normal cranial CT
      scan result is reasonable, but appropriate instructions are required because
      delayed traumatic intracranial hemorrhage may occur.

PMID- 22626016
TI  - Validation of the dime.

PMID- 22626017
TI  - Commentary: Driver electronic device use--put down that cell telephone!

PMID- 22626018
TI  - Change of shift. Spiders.

PMID- 22626019
TI  - Annals of Emergency Medicine Journal Club. Preparing your emergency department
      for the new CMS metrics: collecting and comparing the data: answers to the
      January 2012 Journal Club questions.

PMID- 22626020
TI  - Progressive foot swelling and pain. Posttraumatic dorsalis pedis pseudoaneurysm.

PMID- 22626021
TI  - Public access defibrillation: a call to arms for systematic data collection and
      integration into 911.

PMID- 22626023
TI  - Public access defibrillation.

PMID- 22626025
TI  - Path dependence and the persistence of the Glasgow Coma Scale.

PMID- 22626026
TI  - Male with left lower quadrant abdominal pain. Swallowed wire brush bristle
      foreign body resulting in small bowel perforation.

PMID- 22626027
TI  - Intestinal aganglionosis is associated with early and sustained disruption of the
      colonic microbiome.
AB  - BACKGROUND: Congenital aganglionosis (Hirschsprung's disease) results in colonic
      dysmotility and a risk for Hirschsprung's-associated enterocolitis (HAEC), whose
      cause is unknown. We hypothesized that aganglionosis leads to microbiome changes
      that may contribute to HAEC risk. METHODS: Colon and fecal samples were collected
      from endothelin receptor B-null (Ednrb(-/-) ) mice, an established model of
      colorectal aganglionosis, at postnatal day 7 (P7), P20, and P24. We determined
      microbiome composition by 16S ribosomal RNA gene pyrosequencing and fecal
      metabolite profile by nuclear magnetic resonance spectroscopy. KEY RESULTS: Wild
      type (WT) mice exhibited increasing species diversity with age, with mutant mice
      possessing even greater diversity. WT and mutant microbiomes, both fecal and
      colonic, significantly segregated by principal coordinates analysis based on
      species composition at all ages examined. Importantly, mutant mice contained more
      Bacteroidetes and less Firmicutes than WT, with additional genus- and species
      level differences observed. Notably, mutant P7 colon was dominated by coagulase
      negative Staphylococcus species, which were rare in WT. Mutant fecal metabolite
      profiles also differed, particularly in the abundance of formate, a short-chain
      fatty acid product of microbial fermentation. CONCLUSIONS & INFERENCES:
      Colorectal aganglionosis is associated with early and sustained disruption of the
      normal colonic and fecal microbiome, supporting the enteric nervous system as a
      determinant of microbiome composition. Furthermore, the differences observed
      suggest a potential contributory role for the microbiome in the etiology of HAEC.
      These findings provide a basis for further studies to determine the causative
      role of specific bacterial communities in HAEC and the potential to restore the
      normal microbiome in Hirschsprung's disease.

PMID- 22626028
TI  - Is SPE necessary for environmental analysis? A quantitative comparison of matrix
      effects from large-volume injection and solid-phase extraction based methods.
AB  - Environmental analysis by large-volume injection (LVI) was compared to solid
      phase extraction (SPE) based methods using matrix effects as a quantitative
      indicator of analytical signal quality. LVI was performed by the direct injection
      of 900 MUL of wastewater onto a high-performance liquid chromatography (HPLC)
      column while SPE-based methods utilized octadecyl silane (C18) and hydrophobic
      lypophilic balance (HLB) solid phases to preconcentrate wastewater prior to
      analysis. Model analytes from three classes of environmental contaminants were
      selected for study including four estrogens (estrone, estradiol, estriol, and
      ethinylestradiol), eight perfluoroalkyl carboxylates (C4-C11), and five
      perfluoroalkyl sulfonates (C4, C6-C8, and C10). The matrix effects on analytes
      were assessed by two approaches (quantitatively by calculating percent matrix
      effects and qualitatively with postcolumn infusions) and compared across LVI- and
      SPE-based methods at constant (high and low) analyte-to-matrix mass ratios. The
      results from this study demonstrated that the LVI-based method produced
      analytical signals of quality similar to the two SPE-based methods. Furthermore,
      LVI presented a clear advantage over SPE because it was performed at lower cost,
      required fewer materials, involved less labor and eliminated the analyte loss
      associated with SPE.

PMID- 22626029
TI  - Does journal endorsement of reporting guidelines influence the completeness of
      reporting of health research? A systematic review protocol.
AB  - BACKGROUND: Reporting of health research is often inadequate and incomplete.
      Complete and transparent reporting is imperative to enable readers to assess the
      validity of research findings for use in healthcare and policy decision-making.
      To this end, many guidelines, aimed at improving the quality of health research
      reports, have been developed for reporting a variety of research types. Despite
      efforts, many reporting guidelines are underused. In order to increase their
      uptake, evidence of their effectiveness is important and will provide authors,
      peer reviewers and editors with an important resource for use and implementation
      of pertinent guidance. The objective of this study was to assess whether
      endorsement of reporting guidelines by journals influences the completeness of
      reporting of health studies. METHODS: Guidelines providing a minimum set of items
      to guide authors in reporting a specific type of research, developed with
      explicit methodology, and using a consensus process will be identified from an
      earlier systematic review and from the EQUATOR (Enhancing the QUAlity and
      Transparency Of health Research) Network's reporting guidelines library. MEDLINE,
      EMBASE, the Cochrane Methodology Register and Scopus will be searched for
      evaluations of those reporting guidelines; relevant evaluations from the recently
      conducted CONSORT systematic review will also be included. Single data extraction
      with 10% verification of study characteristics, 20% of outcomes and complete
      verification of aspects of study validity will be carried out. We will include
      evaluations of reporting guidelines that assess the completeness of reporting:
      (1) before and after journal endorsement, and/or (2) between endorsing and non
      endorsing journals. For a given guideline, analyses will be conducted for
      individual and the total sum of items. When possible, standard, pooled effects
      with 99% confidence intervals using random effects models will be calculated.
      DISCUSSION: Evidence on which guidelines have been evaluated and which are
      associated with improved completeness of reporting is important for various
      stakeholders, including editors who consider which guidelines to endorse in their
      journal editorial policies.

PMID- 22626030
TI  - GSK3b-inhibitor lithium chloride enhances activation of Wnt canonical signaling
      and osteoblast differentiation on hydrophilic titanium surfaces.
AB  - AIMS: Promoting bone formation at the tissue interface is an important step to
      improve implant success. This study investigated whether stimulation of Wnt
      signaling by GSK3b inhibitor lithium chloride (LiCl) could affect the response of
      mesenchymal or osteoblastic cells growing on titanium surfaces with different
      topography and wettability, and improve their differentiation along the
      osteoblastic lineage. MATERIAL AND METHODS: Murine mesenchymal C2C12 cells were
      plated on Pickled, acid-etched/sand-blasted (SLA), and hydrophilic SLA titanium
      disks (modSLA) and stimulated with increasing doses of LiCl. Cell viability was
      measured using chemiluminescence-based ATP quantitation and activation of Wnt
      canonical signaling was measured using a Luciferase-based reporter assay. Gene
      expression was measured using real time PCR in C2C12 cells, murine osteoblastic
      MC3T3 cells or murine primary bone marrow cells. RESULTS: LiCl stimulated Wnt
      activation and expression of Wnt markers in C2C12 cells on modSLA. Addition of 1
      mM LiCl increased levels for bone marker Osteocalcin in MC3T3 cells on modSLA
      surfaces. Similarly, LiCl potently enhanced Osteoprotegetrin levels in MC3T3
      cells on modSLA. When primary bone marrow cells were stimulated with LiCl, the
      expression of Wnttarget genes and osteoblastic differentiation markers was
      increased on modSLA surfaces. CONCLUSIONS: Stimulation of the canonical Wnt
      pathway promoted osteoblast differentiation on hydrophilic modSLA surfaces. Taken
      together, these results demonstrate that Wnt activators such as LiCl should be
      further tested as a possible approach to improve implant osseointegration.

PMID- 22626031
TI  - Infant feeding in relation to eating patterns in the second year of life and
      weight status in the fourth year.
AB  - OBJECTIVE: To explore associations of early infant feeding with (i) eating
      patterns in the second year of life and (ii) weight status in the fourth year of
      life in a prospective cohort of children in Scotland. DESIGN: Growing Up in
      Scotland (GUS) longitudinal birth cohort study (2005-2008). SETTING: Scotland,
      UK. SUBJECTS: Children aged 9-12 months (n 5217) followed through to 45-48
      months. RESULTS: Infant feeding was associated with eating patterns, defined by
      using SPSS two-step cluster analysis, in the second year of life. Children who
      were ever breast-fed compared with never breast-fed (adjusted OR = 1.48, 95 % CI
      1.27, 1.73) were more likely to have a positive eating pattern (Cluster 2).
      Children who started complementary feeding at 4-5 months or 6-10 months compared
      with 0-3 months (adjusted OR = 1.32, 95 % CI 1.09, 1.59 or AOR = 1.50, 95 % CI
      1.19, 1.89) were more likely to belong to Cluster 2. Breast-feeding was
      negatively associated with being overweight or obese in the fourth year of life
      compared with no breast-feeding (adjusted OR = 0.81, 95 % CI 0.81, 1.01).
      Introduction of complementary feeding at 4-5 months compared with 0-3 months was
      negatively associated with being overweight or obese (adjusted OR = 0.74, 95 % CI
      0.57, 0.97). CONCLUSIONS: Breast-feeding and introduction of complementary
      feeding after 4 months were associated with a positive eating pattern in the
      second year of life. Introduction of complementary feeding at 4-5 months compared
      with 0-3 months was negatively associated with being overweight or obese.

PMID- 22626033
TI  - The relationship between body composition and physical fitness in 14 year old
      adolescents residing within the Tlokwe local municipality, South Africa: the PAHL
      study.
AB  - BACKGROUND: Little is known about the relationship between body composition and
      physical fitness in 14 year-old high school adolescents of South Africa. Baseline
      data from a longitudinal study on physical activity and health (PAHLS) may
      provide valuable information for future studies, hence to inform public health
      policy makers. The objectives of this study are to determine the prevalence of
      underweight, normal weight and overweight among adolescents aged 14 years in the
      Tlokwe Local Municipality of the North West Province of South Africa, and to
      assess the association between physical fitness and body composition separately
      for boys and girls, adjusted for race and locality. METHODS: Body weight, height
      and triceps, and subscapular skinfolds of 256 adolescents (100 boys and 156
      girls) aged 14 years were measured, and percentage body fat and body mass index
      (BMI) were calculated. BMI was used to determine underweight, normal weight and
      overweight based on the standard criterion. Physical fitness was assessed by
      standing broad jump, bent arm hang and sit-ups according to the EUROFIT fitness
      standard procedures. Multinomial logistic regression analyses stratified for
      gender and adjusted for race (black or white), and the locality (urban or
      township) of the schools were used to analyze the data. RESULTS: In the total
      group 35.9% were underweight and 13.7% overweight. Boys were more underweight
      (44%) than girls (30.7%). The prevalence of overweight was 8% in boys and 17.3%
      in girls. BMI was strongly (p = 0.01) related with percentage body fat. Strong
      and significant positive associations between physical fitness and BMI for the
      underweight girls with high physical fitness scores (OR, 10.69 [95%CI: 2.81
      40.73], and overweight girls with high physical fitness scores (OR, 0.11 [95%CI:
      0.03-0.50]) were found. Non-significant weaker positive relationship between
      physical fitness and BMI for the underweight boys with high physical fitness
      scores (OR, 1.80 [95%CI: 0.63-5.09]), and the overweight boys with high physical
      fitness scores (OR, 0.18 [95%CI: 0.02-1.78]) were found. CONCLUSION: Both
      underweight and overweight among boys and girls in Tlokwe Local Municipality
      exist, and their effects on physical fitness performances were also noticed. As
      such, strategic physical activity, interventions or follow-up studies recognizing
      this relationship particularly in the overweight adolescents are needed. In
      addition, authorities in health and education departments dealing with
      adolescents should make use of this evidence base information in policies
      development.

PMID- 22626034
TI  - GSTP1 and MC1R in melanoma susceptibility.

PMID- 22626035
TI  - The great atopic diseases epidemic: does chemical exposure play a role?

PMID- 22626036
TI  - Winding the clock back on female androgenetic alopecia.

PMID- 22626037
TI  - Minocycline in the management of acne vulgaris: the challenge of conveying
      pharmacovigilance data to primary care.

PMID- 22626038
TI  - The quest for psoriasis susceptibility genes in the postgenome-wide association
      studies era: charting the road ahead.
AB  - The International Psoriasis Council, a global nonprofit organization dedicated to
      advancing psoriasis research and treatment, organized its inaugural genetics
      workshop in Montreal, on 12 October 2011. The presentations included a summary of
      the remarkable progress achieved through the implementation of genome-wide
      association studies, which have highlighted key pathogenic pathways for
      psoriasis. Ongoing meta-analyses are identifying further susceptibility genes,
      bringing the number of known loci close to 40. The functional characterization of
      low-risk alleles is proving problematic, but next-generation sequencing
      approaches are expected to identify rare deleterious variants, which will be
      easier to investigate. Elucidating the genetic architecture of psoriasis will
      have major implications in terms of understanding disease mechanisms and
      predicting response to treatment.

PMID- 22626032
TI  - Characterization of the anaerobic microbial community in oil-polluted subtidal
      sediments: aromatic biodegradation potential after the Prestige oil spill.
AB  - The influence of massive crude oil contamination on the microbial population of
      coastal sediments was investigated in the Cies Islands 18 and 53 months after the
      tanker Prestige sank off the NW coast of Spain. Communities were studied by means
      of culturable and non-culturable methods at three horizons in the sediment (2-5
      cm, 12-15 cm and 25-30 cm) in an area heavily affected by the spill. Most
      probable number of aerobic hydrocarbon degraders was highest in the upper zone
      and decreased dramatically with depth. Aromatic oxidizing nitrate-reducing
      bacteria counts were slightly higher than aerobes in the oxidized layer, and also
      decreased considerably with depth. Iron-reducing bacteria were barely detectable.
      The highest counts were obtained for sulfate-reducing bacteria, which represented
      the most relevant fraction of aromatic oxidizers, being maximal at 12-15 cm
      depth. The community response to high pollution levels was characterized by an
      increase in culturable populations active towards crude oil components despite
      the strong decay in the total cell counts. Analysis of whole 16S rRNA gene
      libraries obtained from the two sampling times and different depths (1460
      sequences in all) showed a predominance of Gamma- and Deltaproteobacteria, which
      was confirmed by fluorescent in situ hybridization. Desulfobacteraceae was the
      most abundant group among Deltaproteobacteria, followed by sequences affiliated
      with the order Myxococcales. All retrieved sequences of this order affiliated
      with a marine myxobacterial clade. Interestingly, sequences affiliated to the
      order Desulfarculales constituted half of the Deltaproteobacteria sequences
      retrieved from the heaviest contaminated sample. Principal coordinates analysis
      of 16S rRNA gene libraries suggested fluctuation in the community distribution
      with time. Changes in the abundance of certain groups such as Bacteroidetes
      contributed to these observed differences. Although predominance of certain
      metabolic types in each horizon could be delimited, a considerable overlap in the
      use of electron acceptors was observed, confirming that each selected zone could
      be influenced by more than one respiratory metabolism. Altogether, our results
      evidence the presence in these sediments of a microbial community with potential
      to respond against hydrocarbon contamination, consistent with the long pollution
      history of the site.

PMID- 22626039
TI  - Mutational analysis of SDCCAG8 in Bardet-Biedl syndrome patients with renal
      involvement and absent polydactyly.
AB  - PURPOSE: To assess for SDCCAG8 mutations in Bardet-Biedl syndrome (BBS) subjects
      with renal involvement and no polydactyly, and to describe phenotypic
      characteristics of SDCCAG8-related disease. MATERIAL AND METHODS: Five patients
      (from 4 pedigrees) with clinical diagnosis of BBS, who had retinal and renal
      involvement and no polydactyly, were assessed. Sequence analysis of SDCCAG8 was
      undertaken and a detailed clinical review of an affected sibship was performed.
      RESULTS: A sibship of East Indian origin who carried a putative clinical
      diagnosis of BBS had compound heterozygous mutations in SDCCAG8
      (p.Thr482LysfsX12/p.Asp543AlafsX24). The renal involvement was early and required
      transplant in both cases. Both were short statured and had asthma since
      childhood. The younger sister also had non-alcoholic fatty liver disease. Visual
      acuity and central fields were preserved in the teenage years in both patients.
      The optical coherence tomography showed preservation of the retinal lamination at
      the fovea; fundus autofluorescence demonstrated a perifoveal ring of
      hyperfluorescence as commonly observed in other forms of retinitis pigmentosa.
      Full-field electroretinogram revealed rod function to be more severely affected
      than cone function in both cases. CONCLUSION: Our results and prior literature
      suggest that SDCCAG8 could play an important role in presumed BBS patients
      affected with severe kidney disease and absent polydactyly. This report enhances
      the phenotypic description of SDCCAG8-related disease.

PMID- 22626041
TI  - The conceit of curriculum.

PMID- 22626042
TI  - Broadening our perceptions of diversity in medical education: using multifocal
      lenses.

PMID- 22626043
TI  - Feedback: the complexity of self-perception and the transition from 'transmit' to
      'received and understood'.

PMID- 22626044
TI  - Clinical reasoning: are we testing what we are teaching?

PMID- 22626045
TI  - Is accreditation a true reflection of quality?

PMID- 22626046
TI  - Improving cultural competence education: the utility of an intersectional
      framework.
AB  - CONTEXT: Most US medical schools have instituted cultural competence education in
      the undergraduate curriculum. This training is intended to improve the quality of
      care that doctors, the majority of whom are White, deliver to ethnic and racial
      minority patients. Research into the outcomes of cultural competence training
      programmes reveals that they have been largely ineffective in improving doctors'
      skills. In varied curricular formats, programmes tend to teach group-specific
      cultural knowledge, despite the vast heterogeneity of racial and ethnic groups.
      This cultural essentialism diminishes training effectiveness. METHODS: This paper
      proposes key curriculum content changes and suggests the inclusion of an
      intersectional framework in the cultural competence curriculum. This framework
      maintains that racial and ethnic minority groups hold multiple social statuses,
      called social locations, which interact with one another to uniquely shape the
      health views, needs and experiences of the individuals within the groups. Social
      locations include those defined by race, ethnicity, gender, social class and
      sexuality, which are experienced multiplicatively, not additively, within a
      particular social context. Cultural competence education must go beyond
      simplified cultural understandings to explore these more complex meanings.
      Doctors' ability to understand, communicate with and treat diverse groups can be
      vastly improved by applying an intersectional framework in academic research,
      self-awareness exercises and clinical training. RESULTS: Integrating an
      intersectional framework into cultural competency education can better prepare
      doctors for caring for racial and ethnic minority patients. This paper recommends
      curriculum elements for the classroom and clinical training that can improve
      doctor knowledge and skills for caring for diverse groups. Medical schools can
      use the proposed model to facilitate the development of new educational
      strategies and learning experiences. These improvements can lead to more
      equitable care and ultimately diminish disparities in health care. Although these
      recommendations are designed with US schools in mind, they may improve doctor
      understanding and care of marginal populations across the world.

PMID- 22626047
TI  - How to construct and implement script concordance tests: insights from a
      systematic review.
AB  - CONTEXT: Programmes of assessment should measure the various components of
      clinical competence. Clinical reasoning has been traditionally assessed using
      written tests and performance-based tests. The script concordance test (SCT) was
      developed to assess clinical data interpretation skills. A recent review of the
      literature examined the validity argument concerning the SCT. Our aim was to
      provide potential users with evidence-based recommendations on how to construct
      and implement an SCT. METHODS: A systematic review of relevant databases
      (MEDLINE, ERIC [Education Resources Information Centre], PsycINFO, the Research
      and Development Resource Base [RDRB, University of Toronto]) and Google Scholar,
      medical education journals and conference proceedings was conducted for
      references in English or French. It was supplemented by ancestry searching and by
      additional references provided by experts. RESULTS: The search yielded 848
      references, of which 80 were analysed. Studies suggest that tests with around 100
      items (25-30 cases), of which 25% are discarded after item analysis, should
      provide reliable scores. Panels with 10-20 members are needed to reach adequate
      precision in terms of estimated reliability. Panellists' responses can be
      analysed by checking for moderate variability among responses. Studies of
      alternative scoring methods are inconclusive, but the traditional scoring method
      is satisfactory. There is little evidence on how best to determine a pass/fail
      threshold for high-stakes examinations. CONCLUSIONS: Our literature search was
      broad and included references from medical education journals not indexed in the
      usual databases, conference abstracts and dissertations. There is good evidence
      on how to construct and implement an SCT for formative purposes or medium-stakes
      course evaluations. Further avenues for research include examining the impact of
      various aspects of SCT construction and implementation on issues such as
      educational impact, correlations with other assessments, and validity of
      pass/fail decisions, particularly for high-stakes examinations.

PMID- 22626048
TI  - Supporting students with disability and health issues: lowering the social
      barriers.
AB  - CONTEXT: Legislation and General Medical Council guidance require medical schools
      to make reasonable adjustments to enable students with disabilities to progress
      in their studies without disadvantage. Current definitions of disability have
      moved from the traditional 'medical' model to a 'social' model that emphasises
      the role of institutions in removing unnecessary barriers to learning through
      flexible provision. In response, two medical schools introduced a Student Support
      Card to empower students with disabilities and health issues to request
      reasonable adjustments. A study was carried out to ascertain the effectiveness of
      the Student Support Card from the user's perspective in both institutions.
      METHODS: A questionnaire survey of card-holders was conducted in 2009-2010. A
      total of 31 respondents took part, from among whom six volunteers were recruited
      to participate in semi-structured interviews. Thematic analysis was conducted and
      data independently analysed by two researchers. RESULTS: The results from the
      questionnaire indicated that the scheme was well received by students and brought
      clear benefits, and that the card's value lay in ownership, as well as in use.
      Further themes emerged from the interviews which suggested that students were
      judicious in requesting adjustments, thus reflecting their concerns over the
      disclosure of disability, the threat that their behaviour might be misinterpreted
      and their acquiring of the competencies necessary to become a doctor.
      CONCLUSIONS: The benefits of such a scheme are that it is flexible and addresses
      unique student needs. Further research needs to focus upon: how educators
      perceive the utility of the Student Support Card; whether it should be embedded
      in the wider medical school culture, and, subsequently, how a working consensus
      can be achieved with regard to reasonable adjustments within vocational education
      in which there are clear requirements for competence.

PMID- 22626049
TI  - Ethnic disparities in undergraduate pre-clinical and clinical performance.
AB  - CONTEXT: Research from numerous medical schools has shown that students from
      ethnic minorities underperform compared with those from the ethnic majority.
      However, little is known about why this underperformance occurs and whether there
      are performance differences among ethnic minority groups. OBJECTIVES: This study
      aimed to investigate underperformance across ethnic minority groups in
      undergraduate pre-clinical and clinical training. METHODS: A longitudinal
      prospective cohort study of progress on a 6-year undergraduate medical course was
      conducted in a Dutch medical school. Participants included 1661 Dutch and 696 non
      Dutch students who entered the course over a consecutive 6-year period (2002
      2007). Main outcome measures were performance in Year 1 and in the pre-clinical
      and clinical courses. Odds ratios (ORs) with 95% confidence intervals (CIs) were
      estimated by logistic regression analysis for ethnic subgroups
      (Surinamese/Antillean, Turkish/Moroccan/African, Asian, Western) compared with
      Dutch students, adjusted for age, gender, pre-university grade point average (pu
      GPA), additional socio-demographic variables (first-generation immigrant, urban
      background, first-generation university student, first language, medical doctor
      as parent) and previous performance at medical school. RESULTS: Compared with
      Dutch students, Surinamese and Antillean students specifically underperformed in
      the Year 1 course (pass rate: 37% versus 64%; adjusted OR 0.40, 95% CI 0.27-0.60)
      and the pre-clinical course (pass rate: 19% versus 41%; adjusted OR 0.57, 95% CI
      0.35-0.93). On the clinical course all non-Dutch subgroups were less likely than
      Dutch students to receive a grade of >= 8.0 (at least three of five grades: 54
      77% versus 88%; adjusted ORs: 0.17-0.45). CONCLUSIONS: Strong ethnic disparities
      exist in medical school performance even after adjusting for age, gender, pu-GPA
      and socio-demographic variables. More subjective grading cannot be ruled out as a
      cause of lower grades in clinical training, but other possible explanations
      should be studied further to mitigate the disparities.

PMID- 22626050
TI  - Medical education accreditation in Mexico and the Philippines: impact on student
      outcomes.
AB  - CONTEXT: Accreditation of medical education programmes is becoming increasingly
      prevalent worldwide, but beyond the face validity of these quality assurance
      methods, data linking accreditation to improved student outcomes are limited.
      Mexico and the Philippines both have voluntary systems of medical education
      accreditation and large numbers of students who voluntarily take components of
      the United States Medical Licensing Examination (USMLE). We investigated the
      examination performance of Mexican and Philippine citizens who attended medical
      schools in their home countries by medical school accreditation status. METHODS:
      The sample included 5045 individuals (1238 from Mexico, 3807 from the
      Philippines) who took at least one of the three USMLE components required for
      Educational Commission for Foreign Medical Graduates (ECFMG) certification. We
      also separately studied 2702 individuals who took all three examinations (589
      from Mexico, 2113 from the Philippines). The chi-squared statistic was used to
      determine whether the associations between outcomes (first attempt pass rate on
      USMLE components and rate of ECFMG certification) and medical school
      accreditation (yes/no) were statistically significant. RESULTS: For the sample of
      registrants who took at least one USMLE component, first attempt pass rates on
      all USMLE components were higher for individuals attending accredited schools,
      although there were differences in pass rates among the components and between
      the two countries. The distinction was greatest for USMLE Step 1, for which
      attending an accredited school was associated with increases in first attempt
      pass rates of 15.9% for Mexican citizens and 29.2% for Philippine citizens. In
      registrants from the Philippines who took all three examinations, attending an
      accredited medical school was also associated with increased success in obtaining
      ECFMG certification. CONCLUSIONS: These findings support the value and usefulness
      of accreditation in Mexico and the Philippines by linking accreditation to
      improved student outcomes.

PMID- 22626051
TI  - Understanding responses to feedback: the potential and limitations of regulatory
      focus theory.
AB  - OBJECTIVES: Regulatory focus theory posits the existence of two systems of self
      regulation underlying human motivation: promotion focus, which is concerned with
      aspirations and accomplishments, and prevention focus, which is concerned with
      obligations and responsibilities. It has been proposed that regulatory focus
      theory may help to explain learners' variable responses to feedback, predicting
      that positive feedback is motivating under promotion focus, whereas negative
      feedback is motivating under prevention focus. We aimed to explore this link
      between regulatory focus theory and response to feedback using data collected in
      a naturalistic setting. METHODS: In a constructivist grounded theory study, we
      interviewed 22 early-career academic doctors about experiences they perceived as
      influential in their learning. Although feedback emerged as important, responses
      to feedback were highly variable. To better understand how feedback becomes (or
      fails to become) influential, we used the theoretical framework of regulatory
      focus to re-examine all descriptions of experiences of receiving and responding
      to feedback. RESULTS: Feedback could be influential or non-influential,
      regardless of its sign (positive or negative). In circumstances in which the
      individual's regulatory focus was readily determined, such as in choosing a
      career (promotion) or preparing for a high-stakes examination (prevention), the
      apparent influence of feedback was consistent with the prediction of regulatory
      focus theory. However, we encountered many challenges in applying regulatory
      focus theory to real feedback scenarios, including the frequent presence of a
      mixed regulatory focus, the potential for regulatory focus to change over time,
      and the competing influences of other factors, such as the perceived credibility
      of the source or content of the feedback. CONCLUSIONS: Regulatory focus theory
      offers a useful, if limited, construct for exploring learners' responses to
      feedback in the clinical setting. The insights and predictions it offers must be
      considered in light of the motivational complexity of clinical learning tasks and
      of other factors influencing the impact of feedback.

PMID- 22626052
TI  - The process of feedback in workplace-based assessment: organisation, delivery,
      continuity.
AB  - OBJECTIVES: Feedback in workplace-based clinical settings often relies on expert
      trainers' judgements of directly observed trainee performance. There is ample
      literature on effective feedback, but in practice trainees in workplace-based
      training are not regularly observed. We aimed to examine external conditions that
      impact feedback in observational workplace-based assessment (WBA). METHODS:
      Interviews were conducted and the resulting data analysed using a qualitative,
      phenomenological approach. Between October 2009 and January 2010, we interviewed
      22 postgraduate general practice trainees at two institutions in the Netherlands.
      Three researchers analysed the transcripts of the interviews. RESULTS: A three
      step scheme emerged from the data. Feedback as part of WBA is of greater benefit
      to trainees if: (i) observation and feedback are planned by the trainee and
      trainer; (ii) the content and delivery of the feedback are adequate, and (iii)
      the trainee uses the feedback to guide his or her learning by linking it to
      learning goals. Negative emotions reported by almost all trainees in relation to
      observation and feedback led to different responses. Some trainees avoided
      observation, whereas others overcame their apprehension and actively sought
      observation and feedback. Active trainers were able to help trainees overcome
      their fears. Four types of trainer-trainee pairs were distinguished according to
      their engagement in observation and feedback. External requirements set by
      training institutions may stimulate inactive trainers and trainees. CONCLUSIONS:
      In line with the literature, our results emphasise the importance of the content
      of feedback and the way it is provided, as well as the importance of its
      incorporation in trainees' learning. Moreover, we highlight the step before the
      actual feedback itself. The way arrangements for feedback are made appears to be
      important to feedback in formative WBA. Finally, we outline several factors that
      influence the success or failure of feedback but precede the process of
      observation and feedback.

PMID- 22626053
TI  - Students' workplace learning in two clerkship models: a multi-site observational
      study.
AB  - CONTEXT: Longitudinal integrated clerkships (LICs) are established, rapidly
      growing models of education designed to improve the core clinical year of medical
      school using guiding principles about workplace learning and continuity. This
      study is the first to report data from direct observations of workplace learning
      experiences of students on LICs and traditional block clerkships (BCs),
      respectively. METHODS: This multi-institution study used an observational, work
      sampling methodology to compare LIC and BC students early and late in the core
      clinical year. Trained research assistants documented students' activities,
      participation (observing, with assistance, alone), and interactions every 10
      minutes over 4-hour periods. Each student was observed one to three times early
      and/or late in the year. Data were aggregated at the student level and by in
      patient or out-patient setting for BC students. One-way analysis of variance
      (anova) was used to compare two groups early in the year (LIC and BC students)
      and three groups late in the year (LIC, out-patient BC and in-patient BC
      students). RESULTS: Early-year observations included 26 students (16 LIC and 10
      BC students); late-year observations included 44 students (28 LIC, eight out
      patient BC and eight in-patient BC students). Out-patient activities and
      interactions of LIC and BC students were similar early in the year, but in the
      later period LIC students spent significantly more time performing direct patient
      care activities alone (25%) compared with out-patient (12%) and in-patient (7%)
      BC students. Students on LICs were significantly more likely to experience
      continuity with patients as 34% of their patients returned to them, whereas only
      5% of patients did so for out-patient BC students late in the year. CONCLUSIONS:
      By late year, LIC students engage in patient care more independently and have
      more opportunities to see clinic patients on multiple occasions than BC students.
      Consistent with the principles of workplace learning, these findings suggest that
      yearlong longitudinal integrated education models, that rely mostly on ambulatory
      settings, afford students greater opportunities to participate more fully in the
      provision of patient care.

PMID- 22626054
TI  - Money is the root of all progress.

PMID- 22626055
TI  - Future direction for research in self-regulated learning in medical education.

PMID- 22626056
TI  - Theoretical foundations of a Starling-like controller for rotary blood pumps.
AB  - A clinically intuitive physiologic controller is desired to improve the
      interaction between implantable rotary blood pumps and the cardiovascular system.
      This controller should restore the Starling mechanism of the heart, thus
      preventing overpumping and underpumping scenarios plaguing their implementation.
      A linear Starling-like controller for pump flow which emulated the response of
      the natural left ventricle (LV) to changes in preload was then derived using pump
      flow pulsatility as the feedback variable. The controller could also adapt the
      control line gradient to accommodate longer-term changes in cardiovascular
      parameters, most importantly LV contractility which caused flow pulsatility to
      move outside predefined limits. To justify the choice of flow pulsatility, four
      different pulsatility measures (pump flow, speed, current, and pump head
      pressure) were investigated as possible surrogates for LV stroke work.
      Simulations using a validated numerical model were used to examine the
      relationships between LV stroke work and these measures. All were approximately
      linear (r(2) (mean +/- SD) = 0.989 +/- 0.013, n = 30) between the limits of
      ventricular suction and opening of the aortic valve. After aortic valve opening,
      the four measures differed greatly in sensitivity to further increases in LV
      stroke work. Pump flow pulsatility showed more correspondence with changes in LV
      stroke work before and after opening of the aortic valve and was least affected
      by changes in the LV and right ventricular (RV) contractility, blood volume,
      peripheral vascular resistance, and heart rate. The system (flow pulsatility)
      response to primary changes in pump flow was then demonstrated to be appropriate
      for stable control of the circulation. As medical practitioners have an
      instinctive understanding of the Starling curve, which is central to the
      synchronization of LV and RV outputs, the intuitiveness of the proposed Starling
      like controller will promote acceptance and enable rational integration into
      patterns of hemodynamic management.

PMID- 22626057
TI  - Role of estrogen treatment in the management of schizophrenia.
AB  - Increasing evidence from epidemiological, preclinical and clinical studies
      suggests that estrogens may exert psychoprotective effects in schizophrenia.
      Observations of gender differences in the onset and course of schizophrenia have
      prompted exploration of the effects of estrogen on the CNS. The aim of this paper
      is to provide an overview of different applications of adjunctive estrogen as a
      possible treatment for symptoms of schizophrenia in both men and women. Recent
      trials have suggested that estrogen augmentation therapy may be able to enhance
      the management of schizophrenia; however, the clinical application of estrogen as
      a treatment has been limited by potential side effects, the most worrying being
      breast and uterine cancer in women, and feminization in men. Selective estrogen
      receptor modulators (SERMs), however, may offer therapeutic benefits for both men
      and women with schizophrenia without posing threat to breast and uterine tissue
      and without feminizing effects. The use of estrogen opens up new possibilities
      for both men and women in the treatment of severe mental illnesses such as
      schizophrenia. With further preclinical and clinical research, it is hoped that
      this promising field of hormone modulation can continue to evolve and eventually
      be translated into real therapeutic potential.

PMID- 22626058
TI  - MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is
      involved in type I interferon production after activation of the antiviral RIG-I
      like receptors.
AB  - BACKGROUND: During a viral infection, the intracellular RIG-I-like receptors
      (RLRs) sense viral RNA and signal through the mitochondrial antiviral signaling
      adaptor MAVS (also known as IPS-1, Cardif and VISA) whose activation triggers a
      rapid production of type I interferons (IFN) and of pro-inflammatory cytokines
      through the transcription factors IRF3/IRF7 and NF-kappaB, respectively. While
      MAVS is essential for this signaling and known to operate through the scaffold
      protein NEMO and the protein kinase TBK1 that phosphorylates IRF3, its mechanism
      of action and regulation remain unclear. RESULTS: We report here that RLR
      activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin
      ligase TRIM25 and marks it for proteasomal degradation concomitantly with
      downstream signaling. Inhibition of this MAVS degradation with a proteasome
      inhibitor does not affect NF-kappaB signaling but it hampers IRF3 activation, and
      NEMO and TBK1, two essential mediators in type I IFN production, are retained at
      the mitochondria. CONCLUSIONS: These results suggest that MAVS functions as a
      recruitment platform that assembles a signaling complex involving NEMO and TBK1,
      and that the proteasome-mediated MAVS degradation is required to release the
      signaling complex into the cytosol, allowing IRF3 phosphorylation by TBK1.

PMID- 22626059
TI  - What are the important subsets of gastroparesis?
AB  - Gastroparesis is often divided into subsets based on etiology and
      pathophysiology; however, the utility of these subsets in the diagnosis and
      treatment of gastro-paresis is not well defined. The objectives are to consider
      the subsets of gastroparesis from the perspectives of etiology and pathogenesis,
      pathophysiology, histopathology, and clinical associations, with particular focus
      on similarities and differences between diabetic and idiopathic gastroparesis and
      consideration of the potential subset of painful gastroparesis. We conclude that
      idiopathic and diabetic gastroparesis has similar initial presentations and
      manifestations, except that idiopathic gastroparesis tends to be associated more
      frequently with pain. Myopathic disorders are uncommon. Extrinsic denervation was
      considered the most common etiology; however, with the decline in surgery for
      peptic ulceration and in-depth study of full-thickness gastric biopsies, the most
      common intrinsic defects are being recognized in the interstitial cells of Cajal
      (ICC-opathy) and with immune infiltration and neuronal changes (intrinsic
      neuropathic gastroparesis). Histomorphological differences at the microscopic
      level between diabetic and idiopathic gastroparesis are still of unclear
      significance. Two gastroparesis subsets worthy of special mention, because they
      are potentially reversible with identification of the cause, are postviral
      gastroparesis, which has a generally good prognosis, and iatrogenic
      gastroparesis, especially in patients with non-surgical gastroparesis, such as
      diabetics exposed to incretins such as pramlintide and exenatide.

PMID- 22626060
TI  - Reciprocal regulation of cholesterol and beta amyloid at the subcellular level in
      Alzheimer's disease.
AB  - Since the discovery that apolipoprotein E, a cholesterol transport protein, is a
      major risk factor for Alzheimer's disease (AD) development, there has been a
      remarkable interest in understanding the many facets of the relationship between
      cholesterol and AD. Several lines of evidence have demonstrated the importance of
      cholesterol in amyloid beta peptide (Abeta) production and metabolism, as well as
      the involvement of Abeta in cholesterol homeostasis. The emerging picture is
      complex and still incomplete. This review discusses findings that indicate that a
      reciprocal regulation exists between Abeta and cholesterol at the subcellular
      level. The pathological impact of such regulation is highlighted.

PMID- 22626061
TI  - Effect of air polishing with glycine powder on titanium abutment surfaces.
AB  - OBJECTIVE: The aim of the present study was to evaluate morphological changes
      induced by glycine powder air polishing on titanium surfaces and its effect on
      bacteria recolonization in comparison with sodium bicarbonate powder. MATERIALS
      AND METHODS: 5 mm wide and 1 mm thick titanium grade II disks were divided into
      three groups of treatments: (i) no treatment; (ii) air polishing with glycine
      powder; (iii) air polishing with sodium bicarbonate powder. Specimens were
      characterized by laser profilometry, scanning electron microscopy (SEM) and then
      installed onto removable appliances worn for 24 h by healthy volunteers. Surface
      contamination was evaluated using SEM and counting the number of colony forming
      units (CFU). RESULTS: SEM observation revealed an increased roughness with the
      formation of craters on samples treated with sodium bicarbonate powder, while not
      in glycine ones. Statistical analysis failed to show significant differences of
      both Ra and Rmax parameters in treated groups. SEM observation of specimens
      surfaces, after 24 h of permanence in the oral cavity, showed a higher
      contamination of the disks treated with sodium bicarbonate compared with those
      not treated (P < 0.05). Conversely, the group treated with glycine showed the
      lower contamination if compared with bicarbonate-treated group (P < 0.05).
      CONCLUSIONS: Air polishing with glycine powder may be considered as a better
      method to remove plaque from dental implant because glycine is less aggressive
      than sodium bicarbonate powder. Moreover, the use of glycine powder seems to have
      an active role on the inhibition of bacterial recolonization of implants in a
      short test period (24 h). Further studies are needed to demonstrate the
      bacteriostatic properties of glycine, envisaged on the basis of reduced
      contamination of the disks polished with glycine compared with those not treated.

PMID- 22626244
TI  - Myocardial contraction and long QT syndrome.
AB  - The long QT syndrome is an inherited cardiac arrhythmic disease that has been
      regarded as a purely electrical disease. However, sporadic reports have indicated
      that myocardial contraction abnormalities are present in these patients. Novel
      echocardiographic techniques such as strain echocardiography have made it
      possible to further elucidate cardiac mechanics in patients with long QT
      syndrome. Here, we provide an overview of current reports on myocardial
      mechanical alterations in patients with long QT syndrome.

PMID- 22626243
TI  - Discrepant regulation of QT (QTc) interval duration by calcium channel blockade
      and angiotensin converting enzyme inhibition in experimental hypertension.
AB  - Antihypertensive treatment may reduce prolonged QT duration in hypertension.
      Generally, the reductions of blood pressure and/or of cardiac mass are believed
      to be the responsible factors. However, drugs are not equivalent in QT modulation
      despite similar antihypertensive and antihypertrophic action. We investigated the
      effect of a calcium channel blocker, lacidipine and an angiotensin-converting
      enzyme inhibitor, enalapril on QT duration in rats. Normotensive Wistar-Kyoto
      rats (WKY) and spontaneously hypertensive rats (SHR) were treated with lacidipine
      (at the dose of 1.5 mg/kg per day for WKY and 3 mg/kg per day for SHR) or
      enalapril (5 mg/kg per day for WKY and 10 mg/kg per day for SHR) during 8 weeks.
      Tail-cuff systolic blood pressure (sBP), left ventricular weight (LVW), vascular
      function of isolated aorta and mesenteric artery and duration of QT (and QTc)
      interval on Frank electrocardiograms were evaluated. As expected, untreated SHR
      showed elevated sBP, impaired vascular reactivity, increased LVW and prolonged QT
      when compared with WKY (p < 0.05). After treatment, both agents markedly improved
      vascular reactivity and reduced sBP in SHR (p < 0.05). Additionally, enalapril
      reduced LVW in both hypertensive (by 17%; p < 0.05) and normotensive rats (by
      13%; p < 0.05) and, consequently, corrected QT duration in SHR. Interestingly,
      lacidipine also reduced LVW in SHR (by 9%; p < 0.05), but without influence on
      prolonged QT. Moreover, lacidipine had no effect on LVW in WKYs but prolonged
      their QT interval (by 10%; p < 0.05). In conclusion, lacidipine did not reverse a
      progressive prolongation of QT in SHR, despite sBP lowering and LVW reduction.
      Thus, the lowering of blood pressure and/or reduction of LVW are not sufficient
      per se to normalize ventricular repolarization in hypertensive cardiac disease.
      More likely, modulation of QT prolongation by antihypertensive drugs is a
      function of their complex action on blood pressure, vascular function, cardiac
      mass and on reflex neurohumoral activation.

PMID- 22626245
TI  - Interplay of defective excitation-contraction coupling, energy starvation, and
      oxidative stress in heart failure.
AB  - In chronic heart failure, maladaptive remodeling of the left ventricle (LV) with
      systolic and diastolic dysfunction underlies the inability of the heart to pump
      sufficient blood to supply the body with blood and oxygen. Three integral aspects
      of this maladaptive LV remodeling are (1) defects in excitation-contraction (EC)
      coupling, particularly of cellular Ca(2+) and Na(+) homeostasis; (2) an energetic
      deficit; and (3) oxidative stress. Although these three aspects are often
      investigated separately from each other, their close and dynamic interplay are
      increasingly recognized. Central to this novel approach are mitochondria, which
      are the main source for cellular ATP, but also for reactive oxygen species, and
      their function is critically regulated by Ca(2+) and Na(+). Here, we review
      recent advances in our understanding of how maladaptive changes of EC coupling
      can contribute to the energetic deficit and oxidative stress, which may initiate
      a vicious cycle leading to progressive cardiac dysfunction.

PMID- 22626246
TI  - Calcium-activated potassium channels, cardiogenesis of pluripotent stem cells,
      and enrichment of pacemaker-like cells.
AB  - Potassium channels represent the largest group of pore proteins regulating
      K(+)efflux from the K(+)-rich inner cell to the extracellular compartment,
      thereby inducing changes in the membrane potential. Activity is regulated either
      by voltage or calcium concentrations, thus the nomenclature of voltage- and
      calcium-activated potassium channels. The critical role of potassium ion channels
      in developmental processes remains enigmatic, although it is well accepted that
      cell differentiation and maturation affect the expression patterns of certain ion
      channels. Recently, a series of studies delineated the precise function of
      calcium-activated potassium channels during cardiac, particularly pacemaker, cell
      development using human and mouse pluripotent stem cell models. It has become
      evident that this protein family not only regulates proliferation, apoptosis, and
      cell metabolism but also drives critical events during organ development such as
      the heart. This review summarizes the literature on calcium-activated potassium
      channels, their role in cardiac stem cell differentiation and development, and
      provides an outlook on how this process could be mechanistically regulated.

PMID- 22626247
TI  - Bioengineered vascular grafts: can we make them off-the-shelf?
AB  - Surgical treatments for vascular disease have progressed during the past century
      from autologous bypass conduits to synthetic materials, animal-derived tissues,
      cryopreserved grafts, and, finally, bioengineered conduits. In all cases,
      alternative vascular grafting materials have been developed with the goal of
      treating patients who have severe vascular disease requiring bypass but who have
      no suitable autologous conduit. Synthetic vascular grafts, animal-derived
      tissues, and cryopreserved grafts all have drawbacks in terms of availability and
      functionality that have limited their routine clinical adoption. Although
      bioengineered vascular graft technologies remain early and highly
      investigational, they have the potential to revolutionize the way in which severe
      vascular disease is treated. However, before they can have a clinical impact,
      bioengineered grafts must be available immediately and "off-the-shelf."

PMID- 22626248
TI  - Antifibrotic effects of omega-3 fatty acids in the heart: one possible treatment
      for diastolic heart failure.
AB  - Half of heart failure patients have diastolic heart failure, which has no
      effective treatments. Several studies indicate a role for omega-3 polyunsaturated
      fatty acids (PUFAs) in heart failure. Recent studies suggest that omega-3 PUFAs
      inhibit cardiac fibrosis and attenuate diastolic dysfunction. This opens up
      possible new avenues for treatment of diastolic heart failure. In this review, we
      focus on the antifibrotic effects of omega-3 PUFAs in heart and the underlying
      cellular and molecular mechanisms.

PMID- 22626249
TI  - Construction of covalent membrane protein complexes and high-throughput selection
      of membrane mimics.
AB  - The association of transmembrane (TM) helices underlies membrane protein
      structure and folding. Structural studies of TM complexes are limited by complex
      stability and the often time-consuming selection of suitable membrane mimics.
      Here, methodology for the efficient, preparative scale construction of covalent
      TM complexes and the concomitant high-throughput selection of membrane mimics is
      introduced. For the employed integrin alphaIIbbeta3 model system, the methodology
      identified phospholipid bicelles, including their specific composition, as the
      best membrane mimic. The method facilitates structure determination by NMR
      spectroscopy as exemplified by the measurement of previously inaccessible
      residual dipolar couplings and (15)N relaxation parameters.

PMID- 22626250
TI  - Site-dependent and state-dependent inhibition of pruritogen-responsive spinal
      neurons by scratching.
AB  - The relief of itch by scratching is thought to involve inhibition of pruritogen
      responsive neurons in the spinal cord. We recorded the responses of superficial
      dorsal horn neurons in mice to intradermal injection of the pruritogens
      chloroquine and histamine. Scratching within an area 5-17 mm distant from the
      injection site, outside of the units' mechanoreceptive fields (off-site),
      significantly inhibited chloroquine-evoked and histamine-evoked responses without
      affecting capsaicin-evoked firing. This is consistent with observations that
      scratching at a distance from a site of itch is antipruritic. In contrast,
      scratching directly at the injection site (within the receptive field; on-site)
      had no effect on chloroquine-evoked neuronal firing, but enhanced the same
      neurons' responses to intradermal injection of the algogen capsaicin. Moreover,
      neuronal responses to histamine were enhanced during on-site scratching, and this
      was followed by suppression of firing below baseline levels after termination of
      scratching. Scratching thus inhibits pruritogen-responsive neurons in a manner
      that depends on the input modality (i.e. pain vs. histamine-dependent or
      histamine-independent itch) and skin location.

PMID- 22626251
TI  - Normograde and retrograde pinning of the distal fragment in feline humeral
      fractures.
AB  - OBJECTIVE: To determine if normograde and retrograde pinning of the distal
      humeral fragment, performed to maximize pin purchase in this fragment, would
      damage vital structures in and around the elbow and shoulder joints in cats.
      STUDY DESIGN: Anatomic study. SAMPLE POPULATION: Cadaveric cats (n = 12; 24
      thoracic limbs). METHODS: Twelve thoracic limb pairs were harvested from domestic
      short-haired cats and 1 limb from each pair was allocated to 1 of 3 groups. A
      transverse osteotomy was created at the junction of the middle and distal thirds
      in the diaphyseal osteotomy group (n = 8) and proximal to the supracondylar
      foramen in the metaphyseal osteotomy group (n = 8). Humeri in the normograde
      group (n = 8) were left intact. Retrograde pinning of the distal fragment in both
      osteotomy groups was performed with the elbow flexed. Pins were driven into the
      medial epicondyle until they exited the skin caudal to the elbow and dissection
      of the soft tissues around the exit tract of the pin was performed. The fracture
      was reduced and the pin was advanced until it exited the proximal humeral
      fragment. In the specimens in normograde group, pinning was initiated on the
      distal aspect of the medial epicondyle. A 1.0 mm guide hole was drilled from the
      medial epicondyle to the center of the medullary cavity of the distal humeral
      metaphysis. A bevelled 1.5 mm IM pin was driven proximally through the guide hole
      until it exited the proximal humerus. RESULTS: Pins exiting the distal aspect of
      the medial epicondyle passed through muscle origins in 5 specimens in the
      diaphyseal osteotomy group and in all 8 specimens in the metaphyseal group. The
      ulnar nerve was entrapped in 1 specimen in both the metaphyseal osteotomy and
      diaphyseal osteotomy groups. The articular cartilage of the trochlea was damaged
      in 5 specimens in the diaphyseal osteotomy group and in 1 specimen in the
      metaphyseal osteotomy group. There was no damage to articular or periarticular
      structures by pins exiting the proximal humerus. CONCLUSION: Retrograde pinning
      of the distal fragment in humeral fractures in the cat may damage the articular
      cartilage and cannot be recommended. Normograde pinning is safe and maximizes pin
      purchase in the distal fragment.

PMID- 22626252
TI  - Emerging themes in uterine natural killer cell heterogeneity and function.
AB  - PROBLEM: Understanding of uterine natural killer (uNK) cell functions during
      normal pregnancy remains incomplete. METHOD OF STUDY: Cloud tag analysis of
      literature was used to document themes addressed experimentally for uNK cells.
      Immunohistochemistry, including whole-mount staining of early implantation sites,
      separation of uNK cells into molecularly distinct subsets, and physiologic
      measurements in normal and mutant mice, are further advancing understanding of
      uNK cell biology. RESULTS: Literature analyses revealed three key, current uNK
      cell research themes: angiogenesis, spiral arterial remodeling/pre
      eclampsia/hypertension and infertility. UNK cells are being defined as cells
      potentially regulated by Wnt signaling that are heterogeneous in progenitor
      source and function and make unique contributions to implantation site
      development prior to spiral arterial remodeling. CONCLUSION: Future studies are
      poised to define uNK cell progenitor cells, identify the signaling pathways
      supporting established uNK cell functions and move current understanding of mouse
      uNK cells to clinical research questions.

PMID- 22626253
TI  - Centimeter-scale colloidal crystal belts via robust self-assembly strategy.
AB  - Centimeter-scale poly(acrylic acid-co-DVB80) (PAA) 3D colloidal crystal belts
      were prepared via a novel robust vertical deposition technique based on negative
      pressure and curvature substrate of the glass vial. The formation of PAA
      colloidal crystal belts was investigated. The results indicated that curvature
      could control the dimension of PAA colloidal crystal belts. Well-controlled
      negative pressure resulted in rapid fabrication of well-defined PAA colloidal
      crystal belts. Curvature substrate of glass vial could distribute shrinking
      stress in the process of drying of colloidal films. Strong hydrogen bonding
      interactions among carboxyl groups on the surface of PAA colloidal particles was
      responsible for PAA colloidal crystal belts with closed-packing characteristics.

PMID- 22626254
TI  - Measurement error of waist circumference: gaps in knowledge.
AB  - OBJECTIVE: It is not clear whether measuring waist circumference in clinical
      practice is problematic because the measurement error is unclear, as well as what
      constitutes a clinically relevant change. The present study aimed to summarize
      what is known from state-of-the-art research. DESIGN: To identify the magnitude
      of the measurement error of waist circumference measurements from the literature,
      a search was conducted in PubMed from 1975 to February 2011. RESULTS: The
      measurement error may vary between 0.7 cm and 15 cm. Taking a realistic range of
      measurable waist circumference into account (60-135 cm), we argue that a short
      term clinically relevant change in waist circumference of 5 % may lie between 3.0
      and 6.8 cm and a maintained clinically relevant change of 3 % between 1.8 and 4.1
      cm. CONCLUSIONS: Based on these results, we conclude it may be difficult to
      distinguish clinically relevant change from measurement error in individual
      subjects, due to the large measurement error and unclear definition of clinically
      relevant change. More research is needed to address these gaps in knowledge. To
      minimize measurement error, we recommend using a uniform measurement protocol,
      training and repeated measurements.

PMID- 22626255
TI  - Systematic evaluation of 99mTc-tetrofosmin versus 99mTc-sestamibi to study murine
      myocardial perfusion in small animal SPECT/CT.
AB  - BACKGROUND: The "back-translation" of clinically available protocols to measure
      myocardial perfusion to preclinical imaging in mouse models of human disease is
      attractive for basic biomedical research. With respect to single-photon emission
      computed tomography (SPECT) approaches, clinical myocardial perfusion imaging
      protocols are established with different 99mTc-labeled perfusion tracers;
      however, studies evaluating and optimizing protocols for these tracers in high
      resolution pinhole SPECT in mice are lacking. This study aims at evaluating two
      clinically available 99mTc-labeled myocardial perfusion tracers (99mTc-sestamibi
      vs. 99mTc-Tetrofosmin) in mice using four different imaging protocols. METHODS:
      Adult C57BL/6 male mice were injected with 99mTc-sestamibi (MIBI) or 99mTc
      Tetrofosmin (TETRO) (4 MBq/g body weight) either intravenously through the tail
      vein (n = 5) or retroorbitally (n = 5) or intraperitoneally (i.p.) under
      anesthesia (n = 3) or i.p. in an awake state (n = 3) at rest. Immediately after
      injection, a multi-frame single-photon emission computed tomography/computed
      tomography (SPECT/CT) acquisition was initiated with six subsequent time frames
      of 10 min each. Reconstructed images of the different protocols were assessed and
      compared by visual analysis by experts and by time-activity-curves generated from
      regions-of-interest for various organs (normalized uptake values). RESULTS:
      Visually assessing overall image quality, the best image quality was found for
      MIBI for both intravenous injection protocols, whereas TETRO only had comparable
      image quality after retroorbital injections. These results were confirmed by
      quantitative analysis where left ventricular (LV) uptake of MIBI after tail vein
      injections was found significantly higher for all time points accompanied with a
      significantly slower washout of 16% for MIBI vs. 33% for TETRO (p = 0.009) from
      10 to 60 min post injection (PI). Interestingly, LV washout from 10 to 60 min PI
      was significantly higher for TETRO when applied by tail vein injections when
      compared to retroorbital injections (22%, p = 0.008). However, liver uptake was
      significant and comparable for both tracers at all time points. Radioactivity
      concentration in the lungs was negligible for all time points and both tracers.
      CONCLUSION: Intravenous MIBI injection (both tail vein and retroorbital) results
      in the best image quality for assessing myocardial perfusion of the murine heart
      by SPECT/CT. TETRO has a comparable image quality only for the retroorbital
      injection route.

PMID- 22626256
TI  - APIC strategic plan 2020.

PMID- 22626257
TI  - The relationship of public health to the infection preventionists in United
      States hospitals, 2011: a partnership for change.
AB  - To gain a better understanding of the relationship between state and local health
      departments and the hospital-based infection prevention community, including the
      potential impact of the American Recovery and Reinvestment Act of 2009 funding on
      those relationships, a survey was developed by the Association for Professionals
      in Infection Control and Epidemiology and the Council of State and Territorial
      Epidemiologists and distributed in 2011. This report describes the survey
      findings and presents an initial assessment of factors identified by infection
      preventionists as the most important in developing an effective relationship with
      health departments. Opportunities for improvement are also described. This
      preliminary analysis provides an initial baseline for further investigation to
      clarify the optimum approaches for ongoing collaboration.

PMID- 22626258
TI  - Pre-marital sexual debut and its associated factors among in-school adolescents
      in Eastern Ethiopia.
AB  - BACKGROUND: More adolescents in Ethiopia are in school today than ever, but few
      studies have assessed the sexual behaviour of these learners. Thus, this study
      tried to assess pre-marital sexual debut and factors associated with it among in
      school adolescents in Eastern Ethiopia. METHODS: A cross-sectional school-based
      study was conducted using a facilitator guided selfadministered questionnaire.
      Respondents were students attending regular school classes in fourteen high
      schools. The proportion of adolescents involved in pre-marital sexual debut and
      the mean age at sexual debut was computed. Factors associated with pre-marital
      sexual debut were assessed using bivariate and multivariable logistic regression.
      RESULTS: About one in four, 686 (24.8%) never married in-school adolescent
      respondents reported pre-marital sexual debut of these 28.8% were males and 14.7%
      were females (p < 0.001). Pre-marital sexual debut was more common among
      adolescents who had their parents in urban areas (Adjusted OR and [95% CI] = 1.42
      [1.17-1.73]), who received higher pocket money per month (Adjusted OR and [95%
      CI] = 1.56 [1.19-2.04]), who perceived low self-educational rank (Adjusted OR and
      [95% CI] = 1.89 [1.07-3.34]) and who lived in rented houses (Adjusted OR and [95%
      CI] = 1.32 [1.03-1.70]). The females and those who were less influenced by
      external pressure were more protected against pre-marital sexual debut (Adjusted
      OR and [95% CI] = 0.44 [0.35-0.56; 0.62 [0.52-0.74, respectively]) than their
      counterparts. CONCLUSION: A significant proportion of in-school adolescents were
      engaged in sexual relationship. Thus, public health interventions should consider
      the broader determinants of premarital sexual debut, including the ecological
      factors in which the behavior occurs.

PMID- 22626260
TI  - NO and ROS homeostasis in mitochondria: a central role for alternative oxidase.

PMID- 22626261
TI  - Out of the light and into the dark: post-illumination respiratory metabolism.

PMID- 22626259
TI  - Discovery of novel PI3-kinase delta specific inhibitors for the treatment of
      rheumatoid arthritis: taming CYP3A4 time-dependent inhibition.
AB  - PI3Kdelta is a lipid kinase and a member of a larger family of enzymes, PI3K
      class IA(alpha, beta, delta) and IB (gamma), which catalyze the phosphorylation
      of PIP2 to PIP3. PI3Kdelta is mainly expressed in leukocytes, where it plays a
      critical, nonredundant role in B cell receptor mediated signaling and provides an
      attractive opportunity to treat diseases where B cell activity is essential,
      e.g., rheumatoid arthritis. We report the discovery of novel, potent, and
      selective PI3Kdelta inhibitors and describe a structural hypothesis for isoform
      (alpha, beta, gamma) selectivity gained from interactions in the affinity pocket.
      The critical component of our initial pharmacophore for isoform selectivity was
      strongly associated with CYP3A4 time-dependent inhibition (TDI). We describe a
      variety of strategies and methods for monitoring and attenuating TDI. Ultimately,
      a structure-based design approach was employed to identify a suitable structural
      replacement for further optimization.

PMID- 22626262
TI  - Recombination, and chromosomes, in a changing environment.

PMID- 22626263
TI  - Powdery mildew genomes in the crosshairs. 2nd International Powdery Mildew
      Workshop and 3rd New Phytologist Workshop, in Zurich, Switzerland, February 2012.

PMID- 22626264
TI  - Sulfur metabolism in archaea reveals novel processes.
AB  - Studies on sulfur metabolism in archaea have revealed many novel enzymes and
      pathways and have advanced our understanding on metabolic processes, not only of
      the archaea, but of biology in general. A variety of dissimilatory sulfur
      metabolisms, i.e. reactions used for energy conservation, are found in archaea
      from both the Crenarchaeota and Euryarchaeota phyla. Although not yet fully
      characterized, major processes include aerobic elemental sulfur (S(0)) oxidation,
      anaerobic S(0) reduction, anaerobic sulfate/sulfite reduction and anaerobic
      respiration of organic sulfur. Assimilatory sulfur metabolism, i.e. reactions
      used for biosynthesis of sulfur-containing compounds, also possesses some novel
      features. Cysteine biosynthesis in some archaea uses a unique tRNA-dependent
      pathway. Fe-S cluster biogenesis in many archaea differs from that in bacteria
      and eukaryotes and requires unidentified components. The eukaryotic ubiquitin
      system is conserved in archaea and involved in both protein degradation and
      biosynthesis of sulfur-containing cofactors. Lastly, specific pathways are
      utilized for the biosynthesis of coenzyme M and coenzyme B, the sulfur-containing
      cofactors required for methanogenesis.

PMID- 22626266
TI  - Glycerol dehydratation by the B12-independent enzyme may not involve the
      migration of a hydroxyl group: a computational study.
AB  - A combination of continuum electrostatic and density functional calculations has
      been employed to study the mechanism of the B(12)-independent glycerol
      dehydratase, a novel glycyl-radical enzyme involved in the microbial conversion
      of glycerol to 3-hydroxylpropionaldehyde. The calculations indicate that the
      dehydratation of glycerol by the B(12)-independent enzyme does not need to
      involve a mechanistically complicated migration of the middle hydroxyl group to
      one of the two terminal positions of a molecule, as previously suggested.
      Instead, the reaction can proceed in three elementary steps. First, a radical
      transfer from the catalytically active Cys433 to the ligand generates a substrate
      related intermediate. Second, a hydroxyl group splits off at the middle position
      of the ligand and is protonated by the neighboring His164 to form a water
      molecule. The other active site residue Glu435 accepts a proton from one of the
      terminal hydroxyl groups of the ligand and a C?O double bond is created. Third,
      the reaction is completed by a radical back transfer from the product-related
      intermediate to Cys433. On the basis of our calculations, the catalytic functions
      of the active site residues have been suggested. Cys433 is a radical relay site;
      His164 and Glu435 make up a proton accepting/donating system; Asn156, His281, and
      Asp447 form a network of hydrogen bonds responsible for the electrostatic
      stabilization of the transition state. A synergistic participation of these
      residues in the reaction seems to be crucial for the catalysis.

PMID- 22626265
TI  - Temporal changes in innate immune signals in a rat model of alcohol withdrawal in
      emotional and cardiorespiratory homeostatic nuclei.
AB  - BACKGROUND: Chronic alcohol use changes the brain's inflammatory state. However,
      there is little work examining the progression of the cytokine response during
      alcohol withdrawal, a period of profound autonomic and emotional upset. This
      study examines the inflammatory response in the central nucleus of the amygdala
      (CeA) and dorsal vagal complex (DVC), brain regions neuroanatomically associated
      with affective and cardiorespiratory regulation in an in vivo rat model of
      withdrawal following a single chronic exposure. METHODS: For qRT-PCR studies, we
      measured the expression of TNF-alpha, NOS-2, Ccl2 (MCP-1), MHC II invariant chain
      CD74, and the TNF receptor Tnfrsf1a in CeA and DVC samples from adult male rats
      exposed to a liquid alcohol diet for thirty-five days and in similarly treated
      animals at four hours and forty-eight hours following alcohol withdrawal. ANOVA
      was used to identify statistically significant treatment effects.
      Immunohistochemistry (IHC) and confocal microscopy were performed in a second set
      of animals during chronic alcohol exposure and subsequent 48-hour withdrawal.
      RESULTS: Following a chronic alcohol exposure, withdrawal resulted in a
      statistically significant increase in the expression of mRNAs specific for innate
      immune markers Ccl2, TNF-alpha, NOS-2, Tnfrsf1a, and CD74. This response was
      present in both the CeA and DVC and most prominent at 48 hours. Confocal IHC of
      samples taken 48 hours into withdrawal demonstrate the presence of TNF-alpha
      staining surrounding cells expressing the neural marker NeuN and endothelial
      cells colabeled with ICAM-1 (CD54) and RECA-1, markers associated with an
      inflammatory response. Again, findings were consistent in both brain regions.
      CONCLUSIONS: This study demonstrates the rapid induction of Ccl2, TNF-alpha, NOS
      2, Tnfrsf1a and CD74 expression during alcohol withdrawal in both the CeA and
      DVC. IHC dual labeling showed an increase in TNF-alpha surrounding neurons and
      ICAM-1 on vascular endothelial cells 48 hours into withdrawal, confirming the
      inflammatory response at the protein level. These findings suggest that an abrupt
      cessation of alcohol intake leads to an acute central nervous system (CNS)
      inflammatory response in these regions that regulate autonomic and emotional
      state.

PMID- 22626268
TI  - Cost analysis of cryotherapy for metastatic disease.

PMID- 22626267
TI  - Percutaneous cryoablation of metastatic lesions from non-small-cell lung
      carcinoma: initial survival, local control, and cost observations.
AB  - PURPOSE: To assess feasibility, complications, local tumor recurrences, overall
      survival (OS), and estimates of cost effectiveness for multisite cryoablation
      (MCA) of oligometastatic non-small-cell lung cancer (NSCLC). MATERIALS AND
      METHODS: A total of 49 computed tomography- and/or ultrasound-guided percutaneous
      MCA procedures were performed on 60 tumors in 31 patients (19 women and 12 men)
      with oligometastatic NSCLC. Average patient age was 65 years. Tumor location was
      grouped according to common metastatic sites. Median OS was determined by Kaplan
      Meier method and defined life-years gained (LYGs). Estimates of MCA costs per LYG
      were compared with established values for systemic therapies. RESULTS: Total
      numbers of tumors and cryoablation procedures for each anatomic site were as
      follows: lung, 20 and 18; liver, nine and seven; superficial, 12 and 11; adrenal,
      seven and seven; paraaortic/isolated, two and two; and bone, 10 and seven. A mean
      of 1.6 procedures per patient were performed, with a median clinical follow-up of
      11 months. Major complication and local recurrence rates were 8% (four of 49) and
      8% (five of 60), respectively. Median OS for MCA was 1.33 years, with an
      estimated 1-year survival rate of approximately 53%. MCA appeared cost-effective
      even when added to the cost of best supportive care or systemic regimens, with an
      adjunctive cost-effectiveness ratio of $49,008-$87,074. CONCLUSIONS: MCA was
      associated with very low morbidity and local tumor recurrence rates for all
      anatomic sites, and possibly increased OS. Even as an adjunct to systemic
      therapies, MCA appeared cost-effective for palliation of oligometastatic NSCLC.

PMID- 22626269
TI  - Magnetic resonance imaging-guided volumetric ablation of symptomatic leiomyomata:
      correlation of imaging with histology.
AB  - PURPOSE: To describe the preliminary safety and accuracy of a magnetic resonance
      (MR) imaging-guided high-intensity-focused ultrasound (HIFU) system employing new
      technical developments, including ablation control via volumetric thermal
      feedback, for the treatment of uterine leiomyomata with histopathologic
      correlation. MATERIALS AND METHODS: In this phase I clinical trial, 11 women
      underwent MR-guided HIFU ablation (Sonalleve 1.5T; Philips Medical Systems,
      Vantaa, Finland), followed by hysterectomy within 30 days. Adverse events,
      imaging findings, and pathologic confirmation of ablation were assessed. The
      relationship between MR imaging findings, thermal dose estimates, and pathology
      and HIFU spatial accuracy were assessed using Bland-Altman analyses and
      intraclass correlations. RESULTS: There were 12 leiomyomata treated. No serious
      adverse events were observed. Two subjects decided against having hysterectomy
      and withdrew from the study before surgery. Of 11 women, 9 underwent
      hysterectomy; all leiomyomata demonstrated treatment in the expected location. A
      mean ablation volume of 6.92 cm(3) +/- 10.7 was observed at histopathologic
      examination. No significant differences between MR imaging nonperfused volumes,
      thermal dose estimates, and histopathology ablation volumes were observed (P >
      .05). Mean misregistration values perpendicular to the ultrasound beam axis were
      0.8 mm +/- 1.2 in feet-head direction and 0.1 mm +/- 1.0 in and left-right
      direction and -0.7 mm +/- 3.1 along the axis. CONCLUSIONS: Safe, accurate
      ablation of uterine leiomyomata was achieved with an MR-guided HIFU system with
      novel treatment monitoring capabilities, including ablation control via
      volumetric thermal feedback.

PMID- 22626270
TI  - Usefulness of material recovered from distal embolic protection devices after
      carotid angioplasty for proteomic studies.
AB  - PURPOSE: To demonstrate the usefulness of biologic material obtained from distal
      embolic protection devices (DEPDs) used in carotid angioplasty for the study of
      atherosclerosis protein markers and to establish the effect of systemic
      inflammation on the protein expression of carotid atheromatous plaques. MATERIALS
      AND METHODS: Two-dimensional gel electrophoresis and mass spectrometry were used
      to study proteins obtained from debris captured in DEPDs from patients who
      underwent carotid angioplasty. In addition, protein expression obtained from
      angioplasty samples in patients with different types of systemic inflammation
      (measured by serum levels of high-sensitivity C-reactive protein [CRP] with a
      cutoff value of 3 mg/L) was compared. Finally, immunohistochemistry of
      atherosclerotic plaques obtained by endarterectomy was used to validate the
      results obtained using DEPDs. RESULTS: Proteomic studies were successfully
      performed using debris from DEPDs. Protein expression differences were found in
      debris from patients with high systemic inflammation compared with debris from
      patients with low systemic inflammation. Annexin A5 (ANXA5), haptoglobin
      precursor, purine nucleoside phosphorylase, transgelin-2 (TAGLN2), and
      bisphosphoglycerate mutase were upregulated in debris from patients with high
      systemic inflammation, and proteasome subunit 8 beta type and glutathione-S
      transferase kappa 1 (GSTK1) levels were higher in debris from patients with low
      levels of systemic inflammation. CONCLUSIONS: Atherosclerotic plaque debris
      captured in DEPDs is a suitable and valid source of material for proteomic
      studies of atherosclerosis. Protein expression in DEPD debris is affected by
      systemic inflammation.

PMID- 22626271
TI  - Usefulness of material recovered from distal embolic protection devices after
      carotid angioplasty: too little, too late?

PMID- 22626272
TI  - Preoperative embolization of primary spinal aneurysmal bone cysts by direct
      percutaneous intralesional injection of n-butyl-2-cyanoacrylate.
AB  - Aneurysmal bone cysts (ABCs) are highly vascular lesions often referred for
      preoperative transarterial embolization. However, accessible arterial pedicles do
      not always exist. Two cases are presented of pediatric patients with spinal ABCs
      in which preoperative embolization was performed by percutaneous injection of up
      to 31 mL of liquid embolic agent (1:7 ratio, n-butyl-2-cyanoacrylate [n-BCA] to
      ethiodized oil). Total estimated surgical blood loss was 1,000 mL in one case and
      3,650 mL in the other case, which occurred during the extensive anterior and
      posterior approaches required to remove the massive ABCs. Direct percutaneous
      injection of n-BCA is a technically simple and efficient adjunct to surgical
      resection with the aim to reduce intraoperative blood loss.

PMID- 22626273
TI  - Transmitted water pump vibration precluding intraprocedural electrocardiographic
      monitoring in juxtacardiac microwave ablation of liver tumor.

PMID- 22626274
TI  - Percutaneous osteoplasty for the treatment of symptomatic subchondral cyst.

PMID- 22626275
TI  - Renal sympathetic denervation: potential role of noncontrast magnetic resonance
      angiography.

PMID- 22626276
TI  - Description of 2 angiogenic phenotypes in clear cell renal cell carcinoma.
AB  - Angiogenesis in clear cell renal cell carcinoma has received recent focus with
      the development of antiangiogenic therapies. Although tumor progression is known
      to be correlated with intratumoral and plasma levels of vascular endothelial
      growth factor-A, the role of tumor induced-angiogenesis remains unclear in these
      tumors. We analyzed the vascular network in a cohort of 73 clear cell renal cell
      carcinoma cases using endothelial immunostaining. We studied protein expression
      of vascular endothelial growth factor, Von Hippel Lindau, and carbonic anhydrase
      IX by immunohistochemistry, Von Hippel Lindau gene alteration by sequencing,
      deletion- and methylation-specific Multiplex Ligation-dependent Probe
      Amplification, and gene expression by pangenomic microarray and quantitative
      polymerase chain reaction in a subcohort of 39 clear cell renal cell carcinoma
      cases. We described 2 distinct angiogenic phenotypes in comparison with the
      normal kidney vasculature: low and high angiogenic phenotypes. The low angiogenic
      phenotype was associated with more aggressive prognostic factors such as T3 to T4
      (62% versus 31%, P=.002), N+ (29% versus 3% P=.004), M+ (53% versus 21%, P=.004)
      stages, Fuhrman grade (grade 3-4: 91% versus 36%, P<.001), and intratumoral
      vascular endothelial growth factor expression (74% versus 28%, P<.001); was less
      associated with Von Hippel Lindau inactivation (56% versus 80%, P=.03); and was a
      predictor of poor prognosis in terms of progression-free, cancer-specific, and
      overall survival (log-rank test, P=.002, P=.011, and P=.035, respectively). The
      low angiogenic phenotype was also associated with a relative down-regulation of
      gene expression (platelet-derived growth factor D, N-acetyl transferase 8, and N
      acetyl transferase 8 B). In conclusion, the histologic and molecular distinction
      between these 2 angiogenic phenotypes could help to better understand the
      biologic behavior of clear cell renal cell carcinoma angiogenesis and could be
      analyzed in a prospective study of the effects of antiangiogenic drugs.

PMID- 22626277
TI  - Involvement of pelvic inflammation-related mismatch repair abnormalities and
      microsatellite instability in the malignant transformation of ovarian
      endometriosis.
AB  - Inflammation in the ovary, including ovulation and pelvic inflammatory disease,
      has been proposed to play a role in the pathogenesis of ovarian cancer.
      Endometriotic lesions trigger a local inflammatory reaction and have been
      reported to be associated with an increased risk of epithelial ovarian cancer.
      However, the precise molecular mechanisms of ovarian cancer arising from
      endometriosis are still to be elucidated. To clarify the involvement of mismatch
      repair (MMR) abnormalities in the inflammation-associated malignant
      transformation of endometriosis, the immunohistochemical expression of mismatch
      repair proteins (human mutL homolog 1 [hMLH1] and human mutS homolog 2 [hMSH2])
      was examined in 27 cases of ovarian endometriosis, 25 cases of ovarian carcinoma
      accompanied by endometriosis, and 39 cases of solitary ovarian carcinoma. In
      addition, the relationship between mismatch repair abnormalities including the
      microsatellite instability, PTEN (phosphatase and tensin homolog) mutation, and
      clinicopathologic parameters was analyzed. The expression of mismatch repair
      proteins was stepwisely decreased in endometriosis, ovarian carcinoma accompanied
      by endometriosis, and ovarian carcinoma. Tumors harboring multiple microsatellite
      instability (high-frequency microsatellite instability [MSI-H]) were detected in
      4 (14.8%) of 27 cases of endometriosis and 7 (30.4%) of 23 cases of ovarian
      carcinomas. The frequency of PTEN mutations was higher in MSI-H cases than in
      microsatellite instability-stable (MSI-S) cases. In 2 cases of ovarian carcinoma
      accompanied by endometriosis, the decreased expression of mismatch repair
      proteins and MSI-H was observed in both the endometriosis and carcinoma lesions.
      Clinicopathologically, the MSI-H cases were associated with elevated serum levels
      of C-reactive protein and higher white blood cell counts. These findings suggest
      that mismatch repair abnormalities might be involved in the malignant
      transformation of ovarian endometriosis and that inflammation induces mismatch
      repair abnormalities during ovarian carcinogenesis arising from endometriosis.

PMID- 22626278
TI  - PTH [1-34] enhances bone response around titanium implants in a rabbit model of
      osteoporosis.
AB  - INTRODUCTION: Dental implant osseointegration can be impaired in medical
      conditions with low bone mass, such as glucocorticoid-induced osteoporosis.
      Intermittent human parathyroid hormone (PTH) [1-34] administration has shown
      relevant anabolic bone activity in various animal models of osteoporosis.
      Therefore, we studied the effects of intermittent PTH [1-34] on bone response
      around titanium implants in experimental osteoporosis induced by ovariectomy and
      glucocorticoid administration. METHODS: Titanium dental implants were placed in
      the proximal tibia metaphysis in 38 animals. Twenty-eight rabbits had undergone
      bilateral ovariectomy and further methylprednisolone administration for 4 weeks
      to induce osteoporosis. Ten healthy rabbits were used as controls. At week 8,
      osteoporotic rabbits started saline vehicle or intermittent PTH administration
      for 12 weeks. Bone mineral density (BMD) was assessed in peri-implant area,
      lumbar spine, and global and subchondral knee bone at baseline, and weeks 6 and
      20. Animal sacrifice was carried out at week 21. Afterward, tibiae were removed
      for MUCT morphometry and undecalcified sections were evaluated by light and
      scanning electron microscopy. RESULTS: PTH increased bone-to-implant contact
      compared with control rabbits or vehicle administration in osteoporotic rabbits
      (P < 0.005). PTH-induced new bone formation around external and internal surfaces
      of titanium implants led to a significant increase of BMD at peri-implant area in
      osteoporotic rabbits at week 20, when compared with vehicle (P < 0.005).
      Likewise, PTH increased BMD in other analysed regions. CONCLUSIONS: Intermittent
      administration of PTH [1-34] enhances the bone response around titanium implants
      in a rabbit model of ovariectomy and glucocorticoid-induced osteoporosis.

PMID- 22626442
TI  - Adaptive and variable intraguild predators facilitate local coexistence in an
      intraguild predation module.
AB  - BACKGROUND: Intraguild predation (IGP) is common in nature, but its ecological
      role is still illusive. A number of studies have investigated a three species IGP
      module that consists of an intraguild predator, intraguild prey, and resource
      species in which the intraguild predator and the intraguild prey exploitatively
      compete for the resource while the intraguild predator also consumes the
      intraguild prey. A common prediction of models of the IGP module is that the
      coexistence of the species is difficult, which is considered inconsistent to the
      ubiquity of IGP in nature. This study revisits the IGP module and provides an
      alternative coexistence mechanism by focusing on a commonly used analysis method
      (i.e., invasion analysis) in light of individual variation in adaptive behavior.
      RESULTS: Invasion analysis underestimates the possibility of coexistence
      regardless of the presence or absence of adaptive behavior. Coexistence is
      possible even when invasion analysis predicts otherwise. The underestimation by
      invasion analysis is pronounced when the intraguild predator forages adaptively,
      which is even further pronounced when the expression of foraging behavior is
      variable among intraguild predators. CONCLUSIONS: The possibility of coexistence
      in the IGP module is greater than previously thought, which may have been partly
      due to how models were analyzed. Inconsistent conclusions may result from the
      same model depending on how the model is analyzed. Individual variation in
      adaptive behavior can be an important factor promoting the coexistence of species
      in IGP modules.

PMID- 22626443
TI  - CD4 costimulation is not required in a novel LPS-enhanced model of myasthenia
      gravis.
AB  - The potential of lipopolysaccharide (LPS) to induce antigen-specific B cell
      responses to acetylcholine receptor (AChR) in myasthenia gravis (MG) was
      evaluated in wild type (WT) and CD4-/- C57BL/6 mice. The WT mice immunized with
      AChR in LPS developed an MG-like disease (LPS-EAMG) similar to that induced by
      immunization with AChR in complete Freund's adjuvant (CFA-EAMG). CD4-/- mice were
      resistant to CFA-EAMG but susceptible to LPS-EAMG. LPS abrogated EAMG resistance
      in CD4-/- mice by increasing high-affinity anti-AChR IgG2b in sera and enhancing
      immune complex deposition in muscle.

PMID- 22626444
TI  - Intranasal inoculation with an adenovirus vaccine encoding ten repeats of Abeta3
      10 reduces AD-like pathology and cognitive impairment in Tg-APPswe/PSEN1dE9 mice.
AB  - To develop a safe and efficient vaccine for AD treatment, we constructed an
      adenovirus vector vaccine encoding ten repeats of Abeta3-10 and CpG motif as a
      molecular adjuvant. We demonstrated that therapeutic immunization with Ad
      10*Abeta3-10-CpG elicits Abeta3-10 specific Th2-polarized immune response with
      high titers of anti-Abeta antibodies in APPswe/PSEN1dE9 mice, which in turn
      reduced Abeta deposits in brains and cognitive impairment. In addition, Ad
      10*Abeta3-10-CpG reduced astrocytosis without increasing the incidence of
      microhemorrhage. Our findings of this study raise the possibility that the
      adenovirus vaccine Ad-10*Abeta3-10-CpG would be a safe and effective alternative
      for AD immunotherapy.

PMID- 22626445
TI  - Transcriptomics: mRNA and alternative splicing.
AB  - Transcriptomics has emerged as a powerful approach for biomarker discovery. In
      the present review, the two main types of high throughput transcriptomic
      technologies - microarrays and next generation sequencing - that can be used to
      identify candidate biomarkers are briefly described. Microarrays, the mainstream
      technology of the last decade, have provided hundreds of valuable datasets in a
      wide variety of diseases including multiple sclerosis (MS), in which this
      approach has been used to disentangle different aspects of its complex
      pathogenesis. RNA-seq, the current next generation sequencing approach, is
      expected to provide similar power as microarrays but extending their capabilities
      to aspects up to now more difficult to analyse such as alternative splicing and
      discovery of novel transcripts.

PMID- 22626446
TI  - Hortonones A to C, hydroazulenones from the genus Hortonia.
AB  - The new hexahydroazulenones hortonones A (1) to C (3) were isolated from the
      leaves of three representative species of the endemic Sri Lankan genus Hortonia
      that belongs to the family Monimiaceae. Hortonones A (1) and B (2) have the
      unprecedented rearranged hortonane sesquiterpenoid carbon skeleton, and hortonone
      C (3) has the unprecedented rearranged and degraded 13-norhortonane skeleton.
      Hortonone C (3) exhibited in vitro cytotoxicity against human breast cancer MCF-7
      cells at 5 MUg/mL.

PMID- 22626447
TI  - Study on the reversible electrode reaction of Na(1-x)Ni(0.5)Mn(0.5)O2 for a
      rechargeable sodium-ion battery.
AB  - Layered NaNi(0.5)Mn(0.5)O(2) (space group: R 3m), having an O3-type (alpha
      NaFeO(2) type) structure according to the Delmas' notation, is prepared by a
      solid-state method. The electrochemical reactivity of NaNi(0.5)Mn(0.5)O(2) is
      examined in an aprotic sodium cell at room temperature. The NaNi(0.5)Mn(0.5)O(2)
      electrodes can deliver ca. 105-125 mAh g(-1) at rates of 240-4.8 mA g(-1) in the
      voltage range of 2.2-3.8 V and show 75% of the initial reversible capacity after
      50 charge/discharge cycling tests. In the voltage range of 2.2-4.5 V, a higher
      reversible capacity of 185 mAh g(-1) is achieved; however, its reversibility is
      insufficient because of the significant expansion of interslab space by charging
      to 4.5 V versus sodium. The reversbility is improved by adding fluoroethylene
      carbonate into the electrolyte solution. The structural transition mechanism of
      Na(1-x)Ni(0.5)Mn(0.5)O(2) is also examined by an ex situ X-ray diffraction method
      combined with X-ray absorption spectroscopy (XAS). The staking sequence of the
      [Ni(0.5)Mn(0.5)]O(2) slabs changes progressively as sodium ions are extracted
      from the crystal lattice. It is observed that the original O3 phase transforms
      into the O'3, P3, P'3, and P3" phases during sodium extraction. XAS measurement
      proves that NaNi(0.5)Mn(0.5)O(2) consists of divalent nickel and tetravalent
      manganese ions. As sodium ions are extracted from the oxide to form Na(1
      x)Ni(0.5)Mn(0.5)O(2), nickel ions are oxidized to the trivalent state, while the
      manganese ions are electrochemically inactive as the tetravalent state.

PMID- 22626448
TI  - Surface ion engineering of Mn2+-doped ZnS quantum dots using ion-exchange resins.
AB  - We report the engineering of surface ions present as defects in doped quantum
      dots (Qdots) following their synthesis. This was achieved by treating the Qdots
      with cation-exchange resin beads (CB). An aqueous dispersion of Mn(2+)-doped ZnS
      Qdots, when treated with different amounts of CB, resulted in two kinds of
      changes in the emission due to Mn(2+) ions. First, the intensity increased in the
      presence of a smaller amount of CB, to the extent of a doubled quantum yield.
      With increased CB as well as incubation time, the emission intensity decreased
      systematically, accompanied by an increasing blue shift of the peak emission
      wavelength. Electron spin resonance results indicated the removal of clusters of
      Mn(2+) present in the Qdots by the CB, which has been attributed to changes in
      the emission characteristics. Transmission electron microscopy studies revealed
      that for smaller amounts of CB there was no change in the particle size, whereas
      for greater amounts the particle size decreased. The results have been explained
      on the basis of the removal of Mn(2+) (and also Zn(2+)) ions present on the
      surfaces of Qdots in the form of clusters as well as individual ions.

PMID- 22626449
TI  - Visual perception of bodily interactions in the primary somatosensory cortex.
AB  - Brain imaging studies in humans have revealed the existence of a visuo-tactile
      system, which matches observed touch with felt touch. In this system, the primary
      somatosensory cortex (SI) appears to play a causal role in the visual processing
      of tactile events. Whether this visuo-tactile mechanism for touch in SI applies
      to the sight of 'any' touch, or whether it is restricted to the domain of body
      related tactile experiences remains unresolved. To address this issue, repetitive
      transcranial magnetic stimulation (rTMS) was used to determine whether activity
      in SI is strictly related to the visual processing of human body-part
      interactions, or is also involved in processing the contact between inanimate
      objects, or between human body-parts and objects. The results show that rTMS over
      SI selectively impaired the processing of a contralateral visual stimulus
      depicting a human body-part being touched by a human agent, while it did not
      affect the visual perception of contact between objects, or between human body
      parts and objects. Correlation analysis shows that this effect was associated
      with the intensity and embodiment of the observed touched. This result suggests
      that SI is more suited to represent social touch, contributing to our
      understanding of the effect of interpersonal tactile interactions between people.

PMID- 22626450
TI  - Correlates of Omani adults' physical inactivity and sitting time.
AB  - OBJECTIVE: To inform public health approaches for chronic disease prevention, the
      present study identified sociodemographic, anthropometric and behavioural
      correlates of work, transport and leisure physical inactivity and sitting time
      among adults in Oman. DESIGN: Cross-sectional study using the WHO STEPwise study
      methodology. SETTING: Sur City, Oman. SUBJECTS: Men and women aged 20 years and
      older (n = 1335) in the Sur City Healthy Lifestyle Study who had complete data
      for demographic variables (gender, age, education, work status and marital
      status), BMI and behavioural risk factors - smoking and dietary habits plus
      physical inactivity and sitting time (the outcome variables). RESULTS: The
      highest level of physical inactivity was in the leisure domain (55.4 %); median
      sitting time was about 2 h/d. Gender-stratified logistic regression models found
      that the statistically significant (P < 0.05) correlates of inactivity (in one or
      more domains) were age, work status and fruit and vegetable intake in women, and
      age, education, work status, marital status and BMI in men. Gender-stratified
      linear regression models found that the statistically significant correlates of
      sitting time were age, work status and BMI in women and education in men.
      CONCLUSIONS: Findings suggest that public health interventions need to be gender
      responsive and focus on domain-specific physical inactivity. In the Omani
      context, this might include gender-segregated exercise facilities to promote
      leisure physical activity among women and walking-friendly environmental
      initiatives to promote transport physical activity among men. Further evidence on
      barriers to physical activity and factors that influence prolonged sitting is
      required to develop relevant public health interventions.

PMID- 22626451
TI  - In vivo multiphoton microscopy technique to reveal the physiology of the mouse
      placenta.
AB  - PROBLEM: Pregnancy is a challenge to the maternal immune system as it must defend
      the body against pathogens while at the same time develop immune tolerance
      against the fetus growing inside the uterus. Despite ex vivo techniques being
      used to understand these processes, in vivo techniques are missing. METHOD OF
      STUDY: To directly study these phenomena, we have developed a new microscope
      stage and surgical procedures for use in two-photon microscopy, for in vivo
      observation of the mouse placenta. RESULTS: These tools and surgical procedures
      demonstrate fetal and maternal blood flow inside the labyrinth zone of the
      placenta, as well as its three dimensional structure. It was also useful to
      identify Plasmodium chabaudi-infected red blood cells inside this labyrinth zone.
      CONCLUSION: We believe this technique will represent an important contribution
      for expanding the available knowledge concerning cell dynamics and interactions
      at the fetal-maternal interface.

PMID- 22626452
TI  - Multicenter case-control study of risk factors for cutaneous melanoma in
      Valencia, Spain.
AB  - INTRODUCTION: It is important to identify subgroups within the general population
      that have an elevated risk of developing cutaneous melanoma because preventive
      and early-detection measures are useful in this setting. The findings of most
      studies that have evaluated risk factors for cutaneous melanoma are of limited
      application in Spain because the populations studied have different pigmentary
      traits and are subject to different environmental factors. OBJECTIVE: To identify
      the phenotypic characteristics and amount of exposure to sunlight that constitute
      risk factors for cutaneous melanoma in the population of the Autonomous Community
      of Valencia, Spain. METHODS: We performed a multicenter observational case
      control study. In total, the study included 242 patients with melanoma undergoing
      treatment in 5 hospitals and 173 controls enrolled from among the companions of
      the patients between January 2007 and June 2008. The information was collected by
      means of a standardized, validated questionnaire. The odds ratio (OR) was
      calculated for each variable and adjusted using a multiple logistic regression
      model. RESULTS: The risk factors found to be statistically significant were skin
      phototypes I and II, blond or red hair, light eye color, abundant melanocytic
      nevi, and a personal history of actinic keratosis or nonmelanoma skin cancer.
      After the multivariate analysis, only blond or red hair (OR=1.9), multiple
      melanocytic nevi (OR=3.1), skin phototypes i and ii (OR=2.1), and a personal
      history of actinic keratosis (OR=3.5) or nonmelanoma skin cancer (OR=8.1)
      maintained significance in the model as independent predictive variables for
      melanoma. CONCLUSIONS: Our study supports the importance of certain factors that
      indicate genetic predisposition (hair color and skin phototype) and environmental
      factors associated with exposure to sunlight. Patients with multiple acquired
      melanocytic nevi and patients with markers of chronic skin sun damage (actinic
      keratosis and nonmelanoma cancer) presented a significant increase in risk.

PMID- 22626453
TI  - Cloned IGH VDJ targets as tools for personalized minimal residual disease
      monitoring in mature lymphoid malignancies; a feasibility study in mantle cell
      lymphoma by the Groupe Ouest Est d'Etude des Leucemies et Autres Maladies du
      Sang.
AB  - Molecular minimal residual disease (MRD) analysis is fast emerging as an
      essential clinical decision-making tool for the treatment and follow-up of mature
      B cell malignancies. Current EuroMRD consensus IGH real-time quantitative
      polymerase chain reaction RQ-PCR assays rely on flow cytometric assessment of
      diagnostic tumour burdens to construct 'normalized', patient-specific, diagnostic
      DNA-based MRD quantification standards. Here, we propose a new 'hybrid' assay
      that relies on plasmid-based quantification of patient-specific IGH VDJ targets
      by consensus IGH real time (RQ)-PCR, combined with EuroMRD guidelines, for MRD
      monitoring in lymphoid malignancies. This assay was evaluated for MRD assessment
      in a total of 273 samples from 29 mantle cell lymphoma (MCL) patients treated
      within a Groupe Ouest Est d'Etude des Leucemies et Autres Maladies du Sang
      (GOELAMS) Phase II trial and was feasible, reliable and consistently comparable
      to gold-standard MRD techniques (99% concordance across all samples including 32
      samples within the quantitative range) when analysed in parallel (117 samples).
      Integrating clinical prognostic parameters and MRD status in peripheral blood at
      the post-induction stage was predictive of progression-free survival (P = 0.034)
      thus demonstrating the clinical utility of the approach. Plasmid-based standards
      for the quantification of IGH VDJ targets are therefore confirmed to offer new
      opportunities for further standardization and clinical evaluation of MRD-guided
      management of patients with mature B cell malignancies.

PMID- 22626454
TI  - [Surgical management of extracranial carotid artery aneurysm].
AB  - OBJECTIVE: Aneurysm of the extracranial carotid artery is rare. The embolic risk
      mandates prompt intervention once diagnosed. The aim of this study was to
      determine therapeutic techniques, their indications and outcomes. PATIENTS AND
      METHODS: We report a series of ten patients who underwent surgery for
      extracranial carotid artery aneurysm in the cardiovascular surgery department of
      La Rabta hospital. RESULTS: There were six men and four women, mean age 43 years.
      All patients were symptomatic (swelling and pulsatile cervical mass). Two
      patients had dysphonia and one patient underwent an emergency procedure because
      of aneurismal rupture. Aneurismal excision was performed in most patients. The
      arterial reconstruction was performed by end-to-end anastomosis in four cases,
      interposition of an autologous venous graft in four, interposition of a
      prosthetic graft in one and suture of a small rent in the artery in one. There
      was no postoperative mortality. Early postoperative morbidity included one
      recurrent laryngeal nerve injury, one hypoglossal nerve injury, one stroke and
      one infection with thrombosis of a prosthetic graft. The follow-up was
      uneventful. CONCLUSION: Surgical treatment of extracranial carotid aneurysms is
      required, in most cases with good results. Endovascular treatment may be an
      effective therapy in selected cases.

PMID- 22626456
TI  - Tertiary butyl hydroperoxide induced oxidative damage in mice erythrocytes:
      Protection by taurine.
AB  - The present study was undertaken to investigate the protective role of taurine,
      against t-butyl hydroperoxide (TBHP) induced oxidative stress in murine
      erythrocytes. Erythrocytes were treated either with TBHP alone or with taurine,
      followed by TBHP exposure. TBHP-induced oxidative stress increased methemoglobin
      formation, lipid peroxidation and protein carbonylation in erythrocytes. The same
      exposure, however, depleted cellular GSH content and altered the activities of
      the antioxidant enzymes as well as of methemoglobin reductase; reduced activities
      of Ca(+) and Na(+)/K(+) ATPase and intracellular ATP levels. Taurine transport
      inhibitor, beta-alanine, treated erythrocytes showed increased phosphatidylserine
      externalization and ROS formation on TBHP exposure and taurine could not revert
      the effect. TBHP exposure increased intracellular calcium and upregulated the
      level of calpain. Administration of taurine could, however, prevent the TBHP
      induced oxidative imbalance. Electron micrographs of erythrocytes showed changed
      morphology with an increase in the number of echinocytes. Taurine treatment could
      restore the normal levels of the antioxidant enzymes and metabolites of the
      erythrocytes. Results suggest that the oxidative insult introduced in
      erythrocytes by TBHP administration is prevented by taurine mainly via membrane
      stabilization.

PMID- 22626455
TI  - Differences in the stimulation of cyclic electron flow in two tropical ferns
      under water stress are related to leaf anatomy.
AB  - Cyclic electron flow (CEF) plays an important role in photoprotection for
      angiosperms under environmental stresses. However, ferns are more sensitive to
      drought and their water transport systems are not as efficient as those of
      angiosperms, it is unclear whether CEF also contributes to photoprotection in
      these plants. Using Microsorum punctatum and Paraleptochillus decurrens, we
      studied the electron fluxes through both photosystem I (PSI) and photosystem II
      (PSII) under water stress and their leaf anatomies. Our goal was to determine if
      CEF functions in the photoprotection of these ferns and, if so, whether CEF
      stimulation is related to leaf anatomy. Compared with P. decurrens, M. punctatum
      had thicker leaves and cuticles and higher water storage capacity, but lower
      stomatal density and slower rate of water loss. During induced drought, the
      decrease in leaf water potential (Psi(leaf) ) was more pronounced in P. decurrens
      than in M. punctatum. For both species, the decline in Psi(leaf)  was associated
      with a lower effective PSII quantum yield, photochemical quantum yield of PSI and
      electron transport rate (ETR), whereas increases were found in the quantum yield
      of regulated energy dissipation, CEF and CEF/ETR(II) ratio. Values for CEF and
      the CEF/ETR(II) ratio peaked in M. punctatum at a light intensity of 500-600 umol
      m(-2)  s(-1)  vs only 150-200 umol m(-2)  s(-1)  in P. decurrens. Therefore, our
      results indicate that the stimulation of CEF in tropical ferns contributes to
      their photoprotection under water stress, and is related to their respective
      drought tolerance and leaf anatomy.

PMID- 22626457
TI  - Hypothermic protection in traumatic brain injury.

PMID- 22626458
TI  - Can erosions on MRI of the sacroiliac joints be reliably detected in patients
      with ankylosing spondylitis? - A cross-sectional study.
AB  - INTRODUCTION: Erosions of the sacroiliac joints (SIJ) on pelvic radiographs of
      patients with ankylosing spondylitis (AS) are an important feature of the
      modified New York classification criteria. However, radiographic SIJ erosions are
      often difficult to identify. Recent studies have shown that erosions can be
      detected also on magnetic resonance imaging (MRI) of the SIJ early in the disease
      course before they can be seen on radiography. The goals of this study were to
      assess the reproducibility of erosion and related features, namely, extended
      erosion (EE) and backfill (BF) of excavated erosion, in the SIJ using a
      standardized MRI methodology. METHODS: Four readers independently assessed T1
      weighted and short tau inversion recovery sequence (STIR) images of the SIJ from
      30 AS patients and 30 controls (15 patients with non-specific back pain and 15
      healthy volunteers) <= 45 years old. Erosions, EE, and BF were recorded according
      to standardized definitions. Reproducibility was assessed by percentage
      concordance among six possible reader pairs, kappa statistics (erosion as binary
      variable) and intraclass correlation coefficient (ICC) (erosion as sum score) for
      all readers jointly. RESULTS: SIJ erosions were detected in all AS patients and
      six controls by >= 2 readers. The median number of SIJ quadrants affected by
      erosion recorded by four readers in 30 AS patients was 8.6 in the iliac and 2.1
      in the sacral joint portion (P < 0.0001). For all 60 subjects and for all four
      readers, the kappa value for erosion was 0.72, 0.73 for EE, and 0.63 for BF. ICC
      for erosion was 0.79, 0.72 for EE, and 0.55 for BF, respectively. For comparison,
      the kappa and ICC values for bone marrow edema were 0.61 and 0.93, respectively.
      CONCLUSIONS: Erosions can be detected on MRI to a comparable degree of
      reliability as bone marrow edema despite the significant heterogeneity of their
      appearance on MRI.

PMID- 22626459
TI  - Temporal variability in the diversity and composition of stream bacterioplankton
      communities.
AB  - Bacterioplankton in freshwater streams play a critical role in stream nutrient
      cycling. Despite their ecological importance, the temporal variability in the
      structure of stream bacterioplankton communities remains understudied. We
      investigated the composition and temporal variability of stream bacterial
      communities and the influence of physicochemical parameters on these communities.
      We used barcoded pyrosequencing to survey bacterial communities in 107
      streamwater samples collected from four locations in the Colorado Rocky Mountains
      from September 2008 to November 2009. The four sampled locations harboured
      distinct communities yet, at each sampling location, there was pronounced
      temporal variability in both community composition and alpha diversity levels.
      These temporal shifts in bacterioplankton community structure were not seasonal;
      rather, their diversity and composition appeared to be driven by intermittent
      changes in various streamwater biogeochemical conditions. Bacterial communities
      varied independently of time, as indicated by the observation that communities in
      samples collected close together in time were no more similar than those
      collected months apart. The temporal turnover in community composition was higher
      than observed in most previously studied microbial, plant or animal communities,
      highlighting the importance of stochastic processes and disturbance events in
      structuring these communities over time. Detailed temporal sampling is important
      if the objective is to monitor microbial community dynamics in pulsed ecosystems
      like streams.

PMID- 22626460
TI  - Rationale for accuracy and consistency in applying standardized definitions for
      surveillance of health care-associated infections.
AB  - As legislative mandates for disclosure of data on health care-associated
      infections (HAIs) to the public escalate, with both economic and reputational
      implications for hospitals, the development of a valid national surveillance
      system has become imperative. Recent studies have identified interinstitutional
      variability of surveillance techniques. These inconsistencies affect the validity
      of publicly reported HAI data, which has as a primary goal the advancement of
      patient safety through the reduction of HAIs. The continued funding of state
      validation studies, the expansion of qualitative research to further assess
      interrater bias, the endorsement of educational materials to assist infection
      preventionists with application of National Healthcare Safety Network criteria,
      and the development of automated surveillance methods are all necessary to ensure
      a national HAI surveillance system that can be used for public reporting.

PMID- 22626461
TI  - An American Journal of Infection Control and National Healthcare Safety Network
      data quality collaboration: a supplement of new case studies.
AB  - The rationale for the case study series is presented, along with results of the
      first 5 American Journal of Infection Control-National Healthcare Safety Network
      case studies. Although the respondents were correct in their assessments more
      often than not, opportunities for improvement remain. Ten new case studies with
      questions are provided. Participants are provided with instructions on how to
      submit responses for continuing education credit through the Centers for Disease
      Control and Prevention. Answers with referenced explanations will be provided
      immediately to those who seek continuing education credit and at a later date via
      the online journal for those who do not.

PMID- 22626462
TI  - Cellular senescence: a double-edged sword in the fight against cancer.
AB  - Over the last few decades, it has become apparent that oncogenic proliferative
      signals are coupled to a variety of growth inhibitory responses, such as the
      induction of apoptotic cell death or irreversible cell cycle arrest known as
      'cellular senescence'. Thus, both apoptosis and cellular senescence are thought
      to act as important tumor suppression mechanisms. Unlike apoptotic cells,
      however, senescent cells remain viable for long periods of time and accumulate
      with increasing age in various organs and tissues. Moreover, recent studies
      reveal that although cellular senescence initially functions as a tumor
      suppressive process, it may eventually exhibit tumor-promoting effects.
      Therefore, it is conceivable that accumulation of senescent cells during the
      ageing process in vivo may contribute to the age-related increase in cancer
      incidence. In this review, we provide an update and perspective on recent
      advances made in understanding the deleterious side effects of cellular
      senescence.

PMID- 22626463
TI  - Oxidative deterioration of platinum nanoparticle and its prevention by palladium.
AB  - Pt nanoparticle is a strong reductant and has been used as an antioxidant in
      cosmetics and medicine. It was reported to have catalase-like activity, which
      converts hydrogen peroxide to water and oxygen. However, in this study, freshly
      prepared Pt nanoparticle was almost inert towards decomposing hydrogen peroxide.
      The catalase-like activity of Pt nanoparticle increased with increasing weeks of
      storage at room temperature and became more significant when the Pt nanoparticle
      was exposed to air. No hydroxyl radical formation was confirmed by several
      methods such as ESR spin-trapping, dimethyl sulphoxide oxidation, salicylic acid
      hydroxylation and hydroxytoluene oxidation, indicating that the decomposition of
      hydrogen peroxide proceeds by the two-electron oxidation/reduction reaction. The
      oxidatively deteriorated Pt nanoparticle catalytically decomposed ascorbic acid,
      which is one of the most important biological antioxidants. We found that such
      oxidation was effectively prevented by the addition of Pd nanoparticle. We also
      discussed the reaction mechanisms and application of Pt nanoparticle.

PMID- 22626465
TI  - Astaxanthin attenuates the UVB-induced secretion of prostaglandin E2 and
      interleukin-8 in human keratinocytes by interrupting MSK1 phosphorylation in a
      ROS depletion-independent manner.
AB  - To elucidate the effects of redox balance regulation on cutaneous inflammation,
      we used the potent antioxidant astaxanthin (AX) to assess its effect on the UVB
      induced secretion of PGE(2) and IL-8 in human keratinocytes and analysed its
      biological mechanism of action. The addition of AX (at 8 MUm) to human
      keratinocytes even after UVB irradiation significantly down-regulated the
      increased secretion of PGE(2) or IL-8. Those suppressive effects were accompanied
      by significantly decreased expression of genes encoding COX-2 or IL-8 as well as
      COX-2 protein. Analysis using a specific NF-kappaB tanslocation inhibitor
      demonstrated that the UVB-stimulated secretion of PGE(2) and IL-8 was
      significantly abolished by its treatment prior to UVB irradiation. Western
      blotting of phosphorylated signalling molecules revealed that UVB irradiation (80
      mJ/cm(2) ) significantly stimulated the phosphorylation of p38, ERK and JNK,
      which was not suppressed by treatment with AX after irradiation. In contrast, AX
      significantly inhibited the UVB-increased phosphorylation of mitogen- and stress
      activated protein kinase (MSK)-1, NF-kBp65 or CREB even when treated
      postirradiation. Further, the MSK1 inhibitor H89 significantly down-regulated the
      increased secretion of PGE(2) and IL-8 in UVB-exposed human keratinocytes,
      following post-irradiation treatment. These findings suggests that AX attenuates
      the auto-phosphorylation of MSK1 required for its activation, which results in
      the decreased phosphorylation of NF-kBp65, which in turn probably leads to a
      deficiency of NF-kB DNA binding activity. This may be associated with the
      significant suppression of PGE(2) /IL-8 secretion via the down-regulated
      expression of COX-2 and IL-8 at the gene and/or protein levels.

PMID- 22626464
TI  - Influence of chemical peeling on the skin stress response system.
AB  - Skin stress response system (SSRS) involves corticotropin-releasing hormone (CRH)
      and proopiomelanocortin (POMC)-derived peptides, such as adrenocorticotropic
      hormone (ACTH), a-melanocyte-stimulating hormone (MSH) and b-endorphin that are
      locally generated in response to locally provided stressors or proinflammatory
      cytokines. This system would restrict tissue damage and restore local
      homoeostasis. Trichloroacetic acid (TCA) is one of the most widely used peeling
      agents and applied for cosmetic treatment of photodamaged skin. However, the
      biological mechanism responsible for TCA peeling has yet to be fully determined.
      While our investigation focused on the inflammation and wound healing pathways,
      in the recent study, we have examined involvement of the SSRS as the third
      pathway. Mostly depending on our findings that TCA peeling activates the SSRS by
      inducing the POMC expression of keratinocytes in the CRH-independent manner,
      together with the results reported by other researchers, we can say that the
      biological effect of POMC seems to be responsible for the TCA-induced epidermal
      SSRS activation.

PMID- 22626466
TI  - Investigation by in vivo reflectance confocal microscopy: melanocytes at the
      edges of solar lentigines.
AB  - In vivo reflectance confocal microscopy (RCM) provides high-resolution, real-time
      optical sections of the skin in a non-invasive manner, allowing visualization of
      the skin in its native state. Highly reflective skin components including
      melanin, collagen and keratin appear bright (white) in RCM images. RCM
      examination of solar lentigines is known to show features that correlate well
      with histologic findings such as supranuclear melanin caps, but there are a
      limited number of reports on melanocyte dendrites. In this study, we utilized RCM
      to investigate the melanocyte dendricity and distribution within solar
      lentigines. Seventeen healthy Japanese females who had fairly large solar
      lentigines on their faces were recruited to join our clinical study, and we
      examined them by using RCM on their non-lesional areas, and the inside and the
      outer rim of the lesional areas. As a result, we discovered that dendritic
      melanocytes were rarely seen in the center of a solar lentigo (SL), but were seen
      at a very high frequency in the outer rim of a SL. The results suggest that the
      melanocytes are more active at the edge of a SL, produce more melanin, and often
      spread their dendrites widely in a horizontal direction. The findings in this
      report might shed light on the dynamic pathomechanisms of solar lentigines in
      vivo.

PMID- 22626467
TI  - Ultraviolet light-induced changes of lymphatic and blood vasculature in skin and
      their molecular mechanisms.
AB  - Ultraviolet light in the 290- to 320-nm wavelength range (UVB) induces
      angiogenesis and lymphatic dysfunction in skin. This review deals with UVB
      induced alterations to the blood and lymphatic systems in skin and the molecular
      mechanisms involved. We also discuss potential strategies to block photoageing of
      skin by inhibiting angiogenesis and/or promoting lymphatic vascular function.

PMID- 22626468
TI  - Mitochondrial common deletion mutation and extrinsic skin ageing in German and
      Japanese women.
AB  - The mitochondrial common deletion (CD) mutation is induced by oxidative stress.
      One main source of oxidative stress is the error-prone process of the respiratory
      chain located in the mitochondria. Another important source is the exposure to
      environmental factors, which further induces oxidative stress in the cells. For
      human skin, the primary damaging environmental factor is ultraviolet (UV)
      radiation, which is able to induce CD mutations and the characteristic extrinsic
      skin ageing signs. Traditionally, levels of UV exposure differ between German and
      Japanese populations, as tanned skin represents beauty and health in Western
      cultures, whereas photo-protected skin is considered ideal in Asia. We
      hypothesize that (i) this cultural-related UV exposure pattern might be reflected
      by CD concentrations in environmentally exposed skin and (ii) CD concentrations
      in environmentally exposed areas might be associated with the manifestation of
      extrinsic skin ageing. In this study, we determined the concentration of CD in
      skin from the neck (environmentally exposed area) and the buttock
      (environmentally protected area) of 22 German and 46 Japanese women between 30
      and 70 years of age. We evaluated skin ageing signs by a validated clinical
      score, and exposure to environmental factors, such as UV exposure and smoking,
      was assessed using a questionnaire-based interview. Higher levels of CD were
      detected in neck skin than in buttock skin in both German and Japanese women. CD
      also increased with age in the neck skin. German women had higher CD
      concentrations in the neck skin than Japanese women. The CD concentrations in the
      buttock skin samples were similar in both populations. These findings suggest
      higher environmental UV exposure resulted in higher levels of CD in the skin of
      German women compared with Japanese women. However, only in Japanese women were
      the signs of extrinsic skin ageing associated with higher CD concentrations in
      the neck skin, in agreement with the hypothesis (ii). In German women, we did not
      find this latter association, which might be due to reaching a maximum level of
      CD, beyond which cells undergo negative selection and are lost to the population
      samples. In conclusion, under some conditions, there seems to be an association
      between the CD mutation concentration and extrinsic skin ageing, but this may be
      modified by cellular and tissue processes which affect the sampling rate for CD
      mutation concentrations and prevent a statistical association with extrinsic skin
      ageing.

PMID- 22626469
TI  - Effect of chemical peeling on the skin in relation to UV irradiation.
AB  - Chemical peeling is one of the dermatological treatments available for certain
      cutaneous diseases and conditions or improvement of cosmetic appearance of
      photoaged skin. However, it needs to be clarified whether the repetitive
      procedure of chemical peeling on photodamaged skin is safe and whether the
      different chemicals used for peeling results in similar outcomes or not. In this
      article, we reviewed the effect of peeling or peeling agents on the skin in
      relation to ultraviolet (UV) radiation. The pretreatment of peeling agents
      usually enhance UV sensitivity by inducing increased sunburn cell formation,
      lowering minimum erythematous dose and increasing cyclobutane pyrimidine dimers.
      However, this sensitivity is reversible and recovers to normal after 1-week
      discontinuation. Using animals, the chronic effect of peeling and peeling agents
      was shown to prevent photocarcinogenesis. There is also an in vitro study using
      culture cells to know the detailed mechanisms of peeling agents, especially on
      cell proliferation and apoptotic changes via activating signalling cascades and
      oxidative stress. It is important to understand the effect of peeling agents on
      photoaged skin and to know how to deal with UV irradiation during the application
      of peeling agents and treatment of chemical peeling in daily life.

PMID- 22626470
TI  - Nuclear factor-kappaB, p53, and mitochondria: regulation of cellular metabolism
      and the Warburg effect.
AB  - Among the characteristics acquired by many tumour cells is a shift from using
      oxidative phosphorylation to using glycolysis for ATP production. Although the
      nuclear factor (NF)-kappaB family of transcriptional regulators have important
      roles in tumorigenesis, their ability to function as regulators of metabolism has
      only been recently investigated. This has revealed the importance of crosstalk
      between NF-kappaB, the p53 tumour suppressor and other crucial cell signalling
      pathways. This review discusses the mechanisms through which NF-kappaB regulates
      tumour cell metabolism and the important role of p53 in determining the
      consequences of NF-kappaB activity. It also proposes a model in which NF-kappaB
      contributes to the shift to glycolytic ATP production through regulation of both
      nuclear and mitochondrial gene expression.

PMID- 22626471
TI  - Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2
      in cancer.
AB  - Cancer cell metabolism is exemplified by high glucose consumption and lactate
      production. Pyruvate kinase (PK), which catalyzes the final step of glycolysis,
      has emerged as a potential regulator of this metabolic phenotype. The M2 isoform
      of PK (PKM2) is highly expressed in cancer cells. However, the mechanisms by
      which PKM2 coordinates high energy requirements with high anabolic activities to
      support cancer cell proliferation are still not completely understood. Current
      research has elucidated novel regulatory mechanisms for PKM2, contributing to its
      important role in cancer. This review summarizes the current understanding and
      explores future directions in the field, highlighting controversies regarding the
      activity and specificity of PKM2 in cancer. In light of this knowledge, the
      potential therapeutic implications and strategies are critically discussed.

PMID- 22626473
TI  - Arsenic in drinking water and acute coronary syndrome in Zrenjanin municipality,
      Serbia.
AB  - BACKGROUND: Arsenic is constantly present in drinking water supply systems of
      Zrenjanin municipality across decades. It presents a great public health problem
      in Serbia, but its relationship with acute coronary syndrome (ACS) has not been
      studied previously. OBJECTIVES: The aims of this study were to assess the
      incidence of ACS in two areas from Zrenjanin municipality consuming different
      levels of arsenic in drinking water, and to explore the association between
      arsenic exposure and the probability of fatal outcome of ACS. METHODS: The
      research was a registry-based ecological study of two populations consuming water
      with different arsenic levels, based on current guidelines (10 MUg/L). Median
      arsenic in the area above national standard was 80 MUg/L; median arsenic in the
      other area was 1 MUg/L. Newly diagnosed cases of ACS were obtained from the
      National Registry for Acute Coronary Syndrome from 2006 to 2010. RESULTS: The two
      populations were comparable by age, gender, and prevalence of risk factors for
      ACS. Standardized incidence rates (SIR) of ACS were higher for people consuming
      arsenic above standard (average five-year SIR was 237.00 per 100.000; 95%
      CI=214.93-260.74), in comparison to people consuming arsenic within limits
      (average SIR=124.40 per 100.000; 95% CI=96.00-158.56). Exposure to arsenic above
      limits was insignificantly associated with fatal outcome of ACS for the whole
      population, men and women. CONCLUSIONS: Consumption of arsenic above national
      standards was associated with higher risk for the occurrence of acute coronary
      syndrome and with insignificantly higher probability of fatal outcome of ACS in
      Zrenjanin municipality.

PMID- 22626472
TI  - Exposure to polycyclic aromatic hydrocarbons and serum inflammatory markers of
      cardiovascular disease.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are environmental and occupational
      carcinogens produced by the incomplete combustion of organic materials, such as
      coal and petroleum product combustion, tobacco smoking, and food cooking, that
      may be significant contributors to the burden of cardiovascular disease in human
      populations. The purpose of this study was to investigate associations between
      ten monohydroxy urinary metabolites of four PAHs and three serum biomarkers of
      cardiovascular disease (fibrinogen, homocysteine, and white blood cell count).
      Using data on 3219 participants aged 20 years and older from the National Health
      and Nutrition Examination Survey (NHANES) 2001-2004 dataset, the associations
      between PAH metabolites and serum inflammatory markers were analyzed using the
      Spearman correlations and multiple linear regression modeling. The PAH
      metabolites of naphthalene, fluorene, phenanthrene, and pyrene each showed both
      positive and negative correlations with homocysteine, fibrinogen, and white blood
      cell count (correlation coefficient range: -0.077-0.143) in nonsmoking
      participants. Using multiple linear regression models adjusted for age, gender,
      race/ethnicity, and body mass index, estimates of weighted geometric means of
      inflammatory marker levels were not significantly different between high and low
      levels (75th vs. 25th percentiles) for all PAH metabolites in nonsmoking
      subjects. The results of this study do not provide evidence for a relationship
      between PAH exposure (as measured by urinary levels of PAH metabolites) and serum
      biomarkers of cardiovascular disease after controlling for tobacco use.

PMID- 22626475
TI  - Autonomic dysfunction and clinical severity of disease in children with allergic
      rhinitis.
AB  - OBJECTIVES: The involvement of autonomic imbalance has been reported in the
      pathogenesis of allergic diseases. PURPOSE: To investigate the association
      between the clinical severity of childhood allergic rhinitis and autonomic
      nervous system (ANS) dysfunction, to define whether the severity of disease
      correlates with ANS activity. METHODS: In this cross-sectional, case-control
      study, we evaluated the ANS testing by measuring sympathetic skin response (SRR)
      and heart rate (R-R) interval variation (RRIV) in 55 children with perennial
      allergic rhinitis (PAR), aged 7-12 yrs without any chronic co-morbidity, and the
      results were compared with 40 sex- and age-matched control subjects. The patients
      were divided into two groups according to the severity of allergic rhinitis.
      RESULTS: There were significant increase in calculated RRIV variables during at
      rest and deep breathing in children with PAR compared to controls, which reflect
      parasympathetic nervous system (PNS) activity (p<0.005). The mean amplitude of
      SSR in patients, which reflect sympathetic nervous system (SNS) activity was
      smaller compared with the controls, but this difference was not significant
      (0.61+/-0.35 MUV vs controls 0.94+/-0.46, p>0.05). Lower RRIV and the prolonged
      SSR latencies in children with AR were closely correlated with disease severity
      (r=-0.65, p<0.05, and r=-0.59, p<0.05 respectively). CONCLUSION: Combined use of
      these two tests, allows separate testing of PNS and SNS function, and are very
      sensitive methods in assessing of severity of disease in children with PAR.

PMID- 22626474
TI  - The prevalence of overweight and obesity, and distribution of waist
      circumference, in adults and children in the French Overseas Territories: the
      PODIUM survey.
AB  - AIM: This study aimed to describe the prevalence of overweight (excluding
      obesity) and obesity, and distribution of waist circumference, in children and
      adults in four French Overseas Territories (Guadeloupe, Martinique, French Guiana
      in the Caribbean and French Polynesia in the Pacific Ocean). METHODS: The survey
      was designed to provide a sample representative of the population in each of the
      four territories. The protocol aimed to evaluate 600 adults (aged >= 15 years)
      and 300 children (aged: 5-14 years) in each territory. RESULTS: In children, the
      differences were small among the territories in the prevalence of overweight
      (excluding obesity), as defined by the International Obesity Task Force (IOTF):
      Guadeloupe, 15.4%; Martinique, 17.0%; French Guiana, 13.2%; and French Polynesia,
      17.2% (P = 0.49). Larger, significant, differences were observed for obesity,
      with prevalences of 7.2%, 7.7%, 5.4% and 15.9%, respectively (P < 0.002). In
      adults, the prevalence of obesity also differed significantly among the
      territories: 22.9%, 22.0%, 17.9% and 33.1% in Guadeloupe, Martinique, French
      Guiana and French Polynesia, respectively (P < 0.001, adjusted for age and
      gender). However, overweight (excluding obesity) was again more homogeneously
      distributed, with prevalences of 31.7%, 33.6%, 30.3% and 34.4%, respectively (P =
      0.43, adjusted for age and gender). Waist circumference was larger in French
      Polynesia than in the other territories in both genders, and in both children and
      adults. CONCLUSION: While the distribution of overweight was relatively
      homogeneous, the prevalence of obesity differed considerably across the four
      territories. It was especially high in French Polynesia, and in children and
      women. Appropriate programmes are urgently needed in these populations,
      especially in children, to avoid the morbidity associated with obesity.

PMID- 22626477
TI  - Still not on the radar: adolescent risk and gambling, revisited.

PMID- 22626478
TI  - Attentional bias and disinhibition toward gaming cues are related to problem
      gaming in male adolescents.
AB  - PURPOSE: The aim of this study was to examine whether behavioral tendencies
      commonly related to addictive behaviors are also related to problematic computer
      and video game playing in adolescents. The study of attentional bias and response
      inhibition, characteristic for addictive disorders, is relevant to the ongoing
      discussion on whether problematic gaming should be classified as an addictive
      disorder. METHODS: We tested the relation between self-reported levels of problem
      gaming and two behavioral domains: attentional bias and response inhibition.
      Ninety-two male adolescents performed two attentional bias tasks (addiction
      Stroop, dot-probe) and a behavioral inhibition task (go/no-go). Self-reported
      problem gaming was measured by the game addiction scale, based on the Diagnostic
      and Statistical Manual of Mental Disorders-fourth edition criteria for
      pathological gambling and time spent on computer and/or video games. RESULTS:
      Male adolescents with higher levels of self-reported problem gaming displayed
      signs of error-related attentional bias to game cues. Higher levels of problem
      gaming were also related to more errors on response inhibition, but only when
      game cues were presented. CONCLUSIONS: These findings are in line with the
      findings of attentional bias reported in clinically recognized addictive
      disorders, such as substance dependence and pathological gambling, and contribute
      to the discussion on the proposed concept of "Addiction and Related Disorders"
      (which may include non-substance-related addictive behaviors) in the Diagnostic
      and Statistical Manual of Mental Disorders-fourth edition.

PMID- 22626479
TI  - Local tobacco policy and tobacco outlet density: associations with youth smoking.
AB  - PURPOSE: This study investigates the associations between local tobacco policy,
      tobacco outlet density, and youth smoking. A primary focus is on whether local
      tobacco policy moderates the relation between outlet density and youth smoking.
      METHODS: In all, 1,491 youth (51.9% male, mean age = 14.7 years, standard
      deviation = 1.05) in 50 midsized California cities were surveyed through a
      computer-assisted telephone interview. Measures of local clean air policy and
      youth access policy were created based on a review of tobacco policies in these
      cities. Outlet density was calculated as the number of retail tobacco outlets per
      10,000 persons, and city characteristics were obtained from 2000 U.S. Census
      data. RESULTS: Using multilevel regression analyses and controlling for city
      characteristics, tobacco outlet density was positively associated with youth
      smoking. No significant main effects were found for the two tobacco policy types
      on any of the smoking outcomes after controlling for interactions and covariates.
      However, statistically significant interactions were found between local clean
      air policy and tobacco outlet density for ever smoked and past 12-month cigarette
      smoking. Comparisons of simple slopes indicated that the positive associations
      between tobacco outlet density and youth smoking behaviors were stronger at the
      lowest level of local clean air policy compared with the moderate and high
      levels. CONCLUSIONS: Our results suggest that tobacco outlet density is related
      to youth smoking. In addition, local clean air policy may act as a moderator of
      relationship between tobacco outlet density and youth smoking, such that density
      is less important at moderate and high levels of this tobacco policy.

PMID- 22626481
TI  - Prevalence and correlates of mental health problems and treatment among
      adolescents seen in primary care.
AB  - PURPOSE: In this study, we describe the characteristics of adolescents with
      mental health problems among those presenting to primary care clinics in urban
      areas. METHODS: The sample included 1,076 adolescents aged 12-18 years who
      presented to federally qualified community health clinics in urban cities in the
      Midwest. Bivariate and multivariate logistic regression analyses were conducted
      to examine the associations between having a mental health problem with
      demographic characteristics, health-related variables, and other risk and
      promotive factors. We also examined the use of health services and involvement in
      activities among those with mental health problems. RESULTS: Approximately 14% of
      adolescents screened positive for a mental health problem; among those with a
      mental health problem, 42.8% received mental health services in the past 3
      months. In the multivariate logistic regression analysis, adolescents who were
      female, with poorer grades, fair to poor self-reported health, using drugs, and
      lower parental monitoring were more likely to have a mental health problem. In
      bivariate analyses, adolescents with mental health problems were less likely to
      participate in school activities and community activities and more likely to use
      emergency room services. CONCLUSIONS: Adolescents with mental health problems
      were more likely to have several other difficulties including poor grades, poor
      self-rated health, drug/alcohol use, and sexual activity. This study highlights
      the importance of screening youth with multidimensional needs and referring them
      to the appropriate services.

PMID- 22626480
TI  - Mental health disorders and long-term opioid use among adolescents and young
      adults with chronic pain.
AB  - PURPOSE: The purpose of this study was to examine the association between mental
      health disorders and subsequent risk for long-term opioid use among adolescents
      and young adults presenting with common chronic pain complaints (back pain, neck
      pain, headache, and arthritis/joint pain). METHODS: Using claims data from
      January 1, 2001 to June 30, 2008, we conducted a longitudinal analysis of opioid
      use patterns among 13-24-year-old subjects presenting with a new episode of
      chronic pain. Long-term opioid use was defined as receiving >90 days of opioids
      within a 6-month period with no gap of >30 days in use of opioids in the 18
      months after the first qualifying pain diagnosis. Mental health disorders were
      identified from claims in the 6 months before the first qualifying pain
      diagnosis. RESULTS: Fifty-nine thousand seventy-seven youth met criteria for a
      new episode of chronic pain. Among these youth, 321 (.5%) met criteria for long
      term opioid use, and 16,172 (27.4%) had some opioid use. After controlling for
      demographic and clinical factors, youth with preexisting mental health diagnoses
      had a 2.4-fold increased risk of subsequently receiving long-term opioids versus
      no opioids (odds ratio = 2.36, 95% confidence interval = 1.73-3.23) and a 1.8
      fold increased likelihood of receiving long-term opioids versus some opioids
      (odds ratio = 1.83, 95% confidence interval = 1.34-2.50). CONCLUSIONS: Mental
      health disorders are associated with increased risk for long-term opioid use
      among adolescents and emerging young adults. Further study is warranted to
      examine risks and benefits of long-term opioid use in this population.

PMID- 22626482
TI  - Contextual amplification or attenuation of pubertal timing effects on depressive
      symptoms among Mexican American girls.
AB  - PURPOSE: To examine the role of neighborhood contextual variation in the putative
      association between pubertal timing and depressive symptoms among Mexican-origin
      girls. METHOD: Mexican-origin girls (N = 344; x(age) = 10.8 years) self-reported
      their total pubertal, adrenal, and gonadal events, along with levels of
      depressive symptoms in the 5th grade. Girls' residential addresses were geocoded
      into neighborhoods, and census data were obtained to describe neighborhoods along
      two dimensions: Hispanic cultural context and socioeconomic disadvantage. Two
      years later, when most of the girls were in the 7th grade, we reassessed the
      girls regarding depressive symptoms. RESULTS: Neighborhood Hispanic composition
      and neighborhood disadvantage were highly positively correlated. Using
      hierarchical linear modeling, we examined the moderating influence of
      neighborhood Hispanic composition and neighborhood disadvantage on the
      prospective associations between pubertal timing (total, gonadal, and adrenal)
      and depressive symptoms. Neighborhood Hispanic composition moderated the
      prospective association between total pubertal and gonadal timing and depressive
      symptoms. Neighborhood disadvantage did not moderate these associations.
      CONCLUSIONS: Our results suggest that early maturing 5th grade Mexican-origin
      girls living in non-Hispanic neighborhoods are at the greatest risk for increased
      depressive symptoms in the 7th grade, even though these neighborhoods tend to be
      socioeconomically more advantaged. The protective cultural context of largely
      Hispanic neighborhoods may outweigh the potential amplifying effects of
      neighborhood disadvantage.

PMID- 22626483
TI  - Understanding the attitudes of Latino parents toward confidential health services
      for teens.
AB  - OBJECTIVES: To explore the knowledge and attitudes that Latino parents have about
      confidential health services for their teens and to identify factors that may
      influence those attitudes. METHODS: Latino parents of teens (12-17 years) were
      randomly selected from a large health maintenance organization and a community
      based hospital to participate in 1-hour focus groups. We conducted eight focus
      groups in the parent's preferred language. Spanish and English transcripts were
      translated and coded with intercoder reliability >80%. RESULTS: There were 52
      participants (30 mothers, 22 fathers). There is a wide range of parental
      knowledge and attitudes about confidential health services for teens. Parents
      believed they had the right to know about their teens' health but were
      uncomfortable discussing sexual topics and thought confidential teen-clinician
      discussions would be helpful. Factors that influence parental acceptability of
      confidential health services include parental trust in the clinician; the
      clinician's interpersonal skills, clinical competencies, and ability to partner
      with parents and teens; and clinician-teen gender concordance. Most parents
      preferred teens' access to confidential services than having their teens forego
      needed care. CONCLUSIONS: This study identifies several underlying issues that
      may influence Latino youths' access to confidential health services. Implications
      for clinical application and future research are discussed.

PMID- 22626484
TI  - Mental distress and subsequent use of psychotropic drugs among adolescents-a
      prospective register linkage study.
AB  - PURPOSE: To investigate the association between mental distress, other factors,
      and subsequent use of psychotropic drugs in adolescents aged 15-16 years.
      METHODS: This study is based on information retrieved from the Norwegian Youth
      Health Surveys (2000-2003) and linked to prescription data from the Norwegian
      Prescription Database (2004-2009). The study population included 11,620
      adolescents aged 15-16 (87% response rate) years. Self-reported mental distress
      (Hopkins Symptom Checklist-10 score 1.85) was recorded along with health and
      lifestyle habits, education plans, and family economics. Incident psychotropic
      drug use (outcome measure) was defined >=1 prescriptions of one of the following
      psychotropic drugs: anxiolytics, hypnotics, antidepressants, or phenothiazines
      registered in the Norwegian Prescription Database. RESULTS: Overall, 15.5% of the
      adolescents reported mental distress, 75% of them were girls. For both genders,
      incident psychotropic use was significantly higher among those reporting mental
      distresses at baseline, compared with the rest of the participants. The highest
      psychotropic drug use was observed among mentally distressed girls (27.7%).
      Mental distress was significantly associated with incident use of psychotropic
      drugs (odds ratio: 2.25, 95% confidence interval: 1.97-2.55). After adjustment
      for confounding factors and inclusion of potential mediating factors, the odds
      ratio attenuated to 1.59 (95% confidence interval: 1.35-1.86). CONCLUSIONS: The
      prevalence of mental distress among adolescents may have consequences for health
      promotion. Public health nurses in Norway, working in health centers and schools,
      have a responsibility to promote health and prevent health problems. They have
      the opportunity and a responsibility to identify vulnerable young people.

PMID- 22626485
TI  - Peer passengers: how do they affect teen crashes?
AB  - PURPOSE: The specific mechanisms by which peer passengers increase teen drivers'
      crash risk are not completely understood. We aimed to provide insight on the two
      primary hypothesized mechanisms, distraction and promotion of risk-taking
      behavior, for male and female teen drivers and further for select driver
      passenger gender combinations. METHODS: From the National Motor Vehicle Crash
      Causation Survey (2005-2007), we analyzed a nationally representative sample of
      677 drivers aged 16-18 years (weighted n = 277,484) involved in serious crashes,
      to compare the risk of specific distraction-related and risk-taking-related
      precrash factors (documented via on-scene crash investigation) for teens driving
      with peer passengers and teens driving alone. RESULTS: Compared with males
      driving alone, those with peer passengers were more likely to perform an
      aggressive act (risk ratio, RR [95% confidence interval] = 2.36 [1.29-4.32]) and
      perform an illegal maneuver (RR = 5.88 [1.81-19.10]) just before crashing; risk
      taking increased regardless of passenger gender. Crash-involved males with
      passengers were also more likely to be distracted by an exterior factor (RR =
      1.70 [1.15-2.51]). Conversely, females with passengers were more often engaged in
      at least one interior nondriving activity (other than conversing with passengers)
      (RR = 3.87 [1.36-11.06]), particularly when driving with opposite-gender
      passengers. Female drivers, both with and without passengers, rarely drove
      aggressively or performed an illegal maneuver before crashing. CONCLUSIONS:
      Passengers may affect male teen driver crashes through both distraction and risk
      promoting pathways, and female involvement primarily through internal
      distraction. Results of this and future studies investigating peer-driver
      interactions may guide development of passenger-related crash prevention efforts
      to complement already existing Graduated Driver Licensing passenger restrictions.

PMID- 22626486
TI  - Validity and reliability of the rapid assessment for adolescent preventive
      services adolescent health risk assessment.
AB  - PURPOSE: Seventy-five percent of adolescent morbidity and mortality is a result
      of risky behaviors. The Rapid Assessment for Adolescent Preventive Services
      (RAAPS) is a 21-question adolescent risk screening tool developed to identify the
      behaviors contributing most to adolescent morbidity, mortality, and social
      problems. The aim of this study was to evaluate the validity and reliability of
      the RAAPS. METHODS: This study used psychometric methods to establish face-,
      content-, and criterion-related validity and inter-rater and equivalence
      reliability. Focus groups with adolescents (n = 21) and health care professionals
      (n = 7) were facilitated to establish face validity. Adolescent expert review (n
      = 10) was gathered to establish content validity and reliability. A retrospective
      chart audit of adolescents (n = 263) who completed both the RAAPS and the
      Guidelines for Adolescent Preventive Services risk questionnaire was conducted to
      assess criterion-related validity and equivalence between paired question
      responses using Cohen kappa measure, percent agreement, and Fisher exact test.
      RESULTS: Face validity was established by consensus of focus group. Adolescent
      expert content validity index scores ranged from 0.825 to 1.0, and inter-rater
      content agreement ranged from 0.9 to 1.0. Cohen kappa ranged from 0.44 to 0.99;
      percent agreement ranged from 0.71 to .99; Fisher exact test resulted in all p >
      0.05 establishing criterion-related validity and equivalence. CONCLUSION:
      Validity and reliability of the RAAPS as a measure of adolescent risk behaviors
      was established. Results indicate RAAPS is an acceptable screening tool in
      identifying adolescent risk behaviors, contributing most to morbidity, mortality,
      and social problems.

PMID- 22626487
TI  - Weight information labels on media models reduce body dissatisfaction in
      adolescent girls.
AB  - PURPOSE: To examine how weight information labels on variously sized media models
      affect (pre)adolescent girls' body perceptions and how they compare themselves
      with media models. METHODS: We used a three (body shape: extremely thin vs. thin
      vs. normal weight) * three (information label: 6-kg underweight vs. 3-kg
      underweight vs. normal weight) experimental design in three age-groups (9-10
      years, 12-13 years, and 15-16 years; n = 184). The girls completed questionnaires
      after exposure to media models. RESULTS: Weight information labels affected
      girls' body dissatisfaction, social comparison with media figures, and
      objectified body consciousness. Respondents exposed to an extremely thin body
      shape labeled to be of "normal weight" were most dissatisfied with their own
      bodies and showed highest levels of objectified body consciousness and comparison
      with media figures. An extremely thin body shape combined with a corresponding
      label (i.e., 6-kg underweight), however, induced less body dissatisfaction and
      less comparison with the media model. Age differences were also found to affect
      body perceptions: adolescent girls showed more negative body perceptions than
      preadolescents. CONCLUSIONS: Weight information labels may counteract the
      generally media-induced thin-body ideal. That is, when the weight labels
      appropriately informed the respondents about the actual thinness of the media
      model's body shape, girls were less affected. Weight information labels also
      instigated a normalization effect when a "normal-weight" label was attached to
      underweight-sized media models. Presenting underweight as a normal body shape,
      clearly increased body dissatisfaction in girls. Results also suggest age between
      preadolescence and adolescence as a critical criterion in responding to media
      models' body shape.

PMID- 22626488
TI  - Developmental trajectories of peer victimization: off-line and online experiences
      during adolescence.
AB  - PURPOSE: This study investigated the development and consequences of off-line and
      online victimization during adolescence. We examined the number and shapes of off
      line and online victimization trajectories, the relationship between trajectories
      of off-line and online victimization, and their effect on life satisfaction.
      METHODS: A four-wave panel study with 6-month time intervals was conducted among
      a representative sample of Dutch adolescents aged 12-17 years (N = 1,762). We
      used group-based modeling to investigate the victimization trajectories. RESULTS:
      Three off-line victimization trajectories could be distinguished. One group
      followed a trajectory of low to no victimization experiences across adolescence.
      A second group followed a pathway of moderate and decreasing victimization. A
      third group followed a pathway of high and decreasing victimization. Two groups
      in online victimization could be distinguished. One group followed a trajectory
      of low to no victimization experiences. A second group followed a pathway of
      moderate victimization that peaked at age 14. Dual-trajectory analyses revealed a
      substantial overlap between off-line and online victimization trajectories.
      Finally, victimization and life satisfaction were longitudinally related;
      moderate and high victimization trajectories resulted in lower levels of life
      satisfaction during wave 4. CONCLUSIONS: The overlap between the off-line and
      online victimization trajectories and their negative consequences on life
      satisfaction suggests that prevention of victimization should focus on both types
      of victimization. The results suggest that peer victimization should not be
      studied without considering adolescent peer relationships on the Internet.

PMID- 22626489
TI  - Lifting the curtain on the conditions of sexual initiation among youth in
      Ethiopia.
AB  - PURPOSE: Deriving accurate estimates of the level of sexual coercion is
      challenging because of the stigma that is attached to the experience. This study
      examines the effectiveness of a nonverbal response-card method to reduce social
      desirability bias in reports of the conditions of sexual initiation among youth
      in southwestern Ethiopia. METHODS: The conditions surrounding sexual initiation
      are examined using data from a pilot survey and a final survey of youth aged 13
      24 years. Half of the respondents in each survey were randomly assigned to a
      nonverbal response-card method for sensitive questions on sexual attitudes and
      behavior, and the other half of the respondents were assigned to a control group
      that provided verbal responses. Responses for the two groups to questions
      regarding the conditions of sexual initiation are compared. RESULTS: Respondents
      who used the nonverbal response card were more likely to report pressure from
      friends or a partner, having sex for money or another gain, and rape as
      conditions of sexual initiation than those who provided verbal responses. Among
      sexually experienced youth, 29.3% of respondents who used the card method
      reported some form of coercion during sexual initiation compared with 19.4% of
      respondents who gave verbal responses. CONCLUSIONS: The nonverbal response card
      provides an effective method for reducing social desirability bias when
      soliciting responses to sensitive questions in the context of an interviewer
      administered survey. The analysis also suggests that coerced sexual initiation is
      underreported by youth in interviewer-administered surveys that use conventional
      verbal responses.

PMID- 22626490
TI  - Is obesity at individual and national level associated with lower age at
      menarche? Evidence from 34 countries in the Health Behaviour in School-aged
      Children Study.
AB  - PURPOSE: A unique standardized international data set from adolescent girls in 34
      countries in Europe and North America participating in the Health Behaviour in
      School-aged Children Study (HBSC) is used to investigate the contribution of body
      mass index (BMI) at individual and country level to cross-national differences in
      age at menarche. METHODS: Two independent nationally representative survey data
      sets from 15-year-olds (n = 27,878, in 34 countries, year = 2005/2006) and 11
      year-olds (n = 18,101, in 29 countries, year = 2001/2002) were analyzed. The
      survey instrument is a self-report questionnaire. Median age at menarche and 95%
      confidence intervals (CIs) were estimated using Kaplan-Meier analysis.
      Hierarchical models were used to assess the relationship between BMI and age at
      menarche (months). "Country-level obesity" was measured by prevalence of
      overweight/obesity (%) in each country. RESULTS: Country-level median age at
      menarche ranged between 12 years and 5 months and 13 years and 5 months. Country
      level prevalence of overweight among 15-year-old girls ranged from 4% to 28%. Age
      at menarche was inversely associated with individual BMI (unstandardized
      regression coefficient beta = -1.01; 95% CI, -1.09 to -.94) and country-level
      aggregate overweight at age 11 (unstandardized regression coefficient beta = 
      .25; 95% CI, -.43 to -.08). Individual- and country-level measures of BMI account
      for 40% of the country-level variance in age at menarche. CONCLUSIONS: The
      findings add to the evidence that obesity in childhood is a risk factor for early
      puberty in girls and accounts for much of the cross-national variation in age at
      menarche. Future HBSC surveys can track this relationship in the wake of the
      obesity "epidemic."

PMID- 22626492
TI  - Factors associated with adolescents' propensity to drive with multiple passengers
      and to engage in risky driving behaviors.
AB  - PURPOSE: Research shows that parenting factors and individual difference
      variables, such as sensation seeking (SS) and risk perceptions (RPs), are
      associated with increased motor vehicle crash risk for young drivers. The
      presence of peer passengers is also known to be associated with increased crash
      risk. However, as previous studies did not study these factors concurrently, less
      is known about the factors that are associated with driving with peer passengers
      and if peer passengers may mediate the effect of parenting and individual
      difference variables on adolescents' engagement in risky driving behavior.
      METHODS: We examined predictors of driving with multiple passengers (DWMPs) and
      explored it as a potential mediator of pathways from three factors: (1) SS, (2)
      RPs, and (3) Parental monitoring and rule-setting to risky driving behaviors in a
      convenience sample of 198 adolescent drivers using a cross-sectional Web-based
      survey. RESULTS: Findings indicate that both stronger RPs and perceiving parents
      as strong monitors and rule setters were associated with less engagement in risky
      driving, whereas greater SS was associated with more engagement in risky driving;
      RPs, monitoring, and SS were also significantly associated with DWMPs in these
      same directions. DWMPs partially mediated the effect of these risk factors on
      risky driving behavior. CONCLUSIONS: Results inform theory and policy by
      examining factors associated with risk taking in the context of adolescent
      driving. Interventions can be developed to complement graduated driver licensing
      laws by targeting individual difference variables and decreasing opportunities
      for peer passenger carriage.

PMID- 22626491
TI  - Engaging parents in the family check-up in middle school: longitudinal effects on
      family conflict and problem behavior through the high school transition.
AB  - PURPOSE: Adolescence is a time of significant developmental change. During this
      period, levels of problem behavior that had been relatively innocuous may
      escalate in the company of peers, with simultaneous reductions in parental
      monitoring and involvement. In this article, we report the results of a
      randomized controlled trial of the Family Check-Up (FCU), a family-centered,
      school-based intervention designed to forestall the escalation of adolescent
      problem behavior by promoting and motivating skillful parenting through the
      transition to high school. METHODS: In this study, 593 ethnically diverse
      families were randomized to be offered the FCU when their youth were in seventh
      and eighth grades of middle school. We used complier average causal effect
      analysis to examine change in family conflict, antisocial behavior, involvement
      with deviant peers, and alcohol use from sixth through ninth grades. RESULTS:
      Analyses revealed that when compared with a matched control group, youths whose
      parents had engaged in the FCU demonstrated significantly lower rates of growth
      in family conflict (p = .052), antisocial behavior, involvement with deviant
      peers, and alcohol use. DISCUSSION: Our results extend current research on the
      FCU and provide support for theory that links family conflict with a variety of
      youth problem behavior. These results and the extant research on the FCU suggest
      that traditional school-based service delivery models that focus on the
      individual child may benefit from a shift in perspective to engage parents and
      families.

PMID- 22626493
TI  - Course of life into adulthood of patients with biliary atresia: the achievement
      of developmental milestones in a nationwide cohort.
AB  - PURPOSE: To investigate the course of life of young adults diagnosed with biliary
      atresia (BA) in infancy by comparing patients who did and did not underwent
      transplantation with an age-matched Dutch reference group. METHODS: All patients
      from the Dutch BA registry, aged >18 years, were invited to complete the course
      of life questionnaire. RESULTS: Forty patients participated (response = 74%).
      Twenty-five had not undergone transplantation; 15 had undergone orthotopic liver
      transplantation. One significant between-group difference was found, namely in
      substance use and gambling. BA patients who underwent transplantation reported
      less use than the reference group (p = .01, moderate effect size). Additional
      moderate effect sizes were found for differences in psychosexual and social
      development and antisocial behavior. Patients who underwent transplantation had
      lower scores than one or both other groups. CONCLUSIONS: Development of BA
      survivors who did not undergo transplantation seems not delayed, whereas that of
      transplanted patients does seem somewhat delayed. However, patients who underwent
      transplantation display less risk behavior. Larger samples are necessary to
      confirm these findings.

PMID- 22626494
TI  - Uncorrected distance visual impairment among adolescents in the United States.
AB  - PURPOSE: To describe uncorrected distance visual impairment (VI). METHODS: We
      conducted an analysis of the 3,555 adolescents aged 12 through 21 years who
      participated in the 2005-2008 National Health and Nutrition Examination Survey.
      Distance VI was defined as 20/40 or worse in the better-seeing eye. Data were
      weighted to represent the civilian noninstitutionalized population. RESULTS:
      Overall, 12.3% (95% confidence interval [CI]: 10.7%-14.1%) had distance VI, which
      was correctable to 20/30 or better in both eyes in 86.1% (95% CI: 83.6%-89.5%).
      The prevalence was higher among those who reported not having corrective lenses
      available (44.3%) compared with those who reported that they did not need them
      (8.5%) or who had them available (5.2%; p < .001). After adjusting for potential
      confounders, those who were 12 or 13 years of age had 2.27 (95% CI: 1.32-3.90)
      greater odds of distance VI than older adolescents, and the odds of distance VI
      were greater among non-Hispanic blacks (1.66 [95% CI: 1.11-2.48]), Hispanics
      (1.96 [95% CI: 1.35-2.84]), or other race/ethnicities (2.06 [95% CI: 1.19-3.57])
      than among non-Hispanic whites. CONCLUSIONS: More than 1 in 10 adolescents had
      uncorrected distance VI. To address this, interventions should address case
      detection, access to eye care, and adherence with corrective lenses.

PMID- 22626495
TI  - Hospitalization for underage drinkers in the United States.
AB  - PURPOSE: Underage drinking is common in the United States. This article presents
      nationally representative data on hospitalizations for alcohol use disorder (AUD)
      in youth. METHODS: Using the Nationwide Inpatient Sample database, discharge
      records of individuals between 15 and 20 years diagnosed with AUD were
      identified. Incidence rates of these hospitalizations were calculated based on
      population estimates from the US Census Bureau. RESULTS: In 2008, there were
      699,506 nonobstetric discharges in 15- to 20-year-olds, of which 39,619 (5.6%)
      had an AUD diagnosis with or without an injury diagnosis. The overall annual
      incidence of AUD hospitalization was 18.3 per 10,000 boys and 12.3 per 10,000
      girls. Native American boys in the Midwest had the highest incidence (101 per
      10,000), and Asian/Pacific Islander girls in the South had the lowest (2 per
      10,000). The estimated total charges for these hospitalizations were $755 million
      in 2008. CONCLUSIONS: Hospitalization care for underage drinking is common,
      especially in certain race and in certain geographic regions and is associated
      with a substantial health care expenditure.

PMID- 22626498
TI  - Substance use, sexual intercourse, and condom nonuse among depressed adolescents
      and young adults: scientific views.

PMID- 22626496
TI  - Relationships between body satisfaction and psychological functioning and weight
      related cognitions and behaviors in overweight adolescents.
AB  - PURPOSE: To examine how differences in body satisfaction may influence weight
      control behaviors, eating, weight and shape concerns, and psychological well
      being among overweight adolescents. METHODS: A group of 103 overweight
      adolescents completed a survey assessing body satisfaction, weight control
      behaviors, eating-related thoughts and behaviors, importance placed on thinness,
      self-esteem, anger, and symptoms of depression and anxiety between 2004 and 2006.
      Logistic regression analyses compared overweight adolescents with high and low
      body satisfaction. RESULTS: Higher body satisfaction was associated with a lower
      likelihood of engaging in unhealthy weight control behaviors, less frequent fears
      of losing control over eating, and less importance placed on thinness. Overweight
      adolescents with higher body satisfaction reported higher levels of self-esteem
      and were less likely to endorse symptoms of depression, anxiety, and anger than
      overweight adolescents with lower body satisfaction. CONCLUSIONS: Adolescents
      with higher body satisfaction may be protected against the negative behavioral
      and psychological factors associated with overweight.

PMID- 22626499
TI  - Magnetic nanosized {M(II)24}-wheel-based (M = Co, Ni) coordination polymers.
AB  - Two 3D coordination polymers,
      [Co(24)(OH)(12)(SO(4))(12)(ip)(6)(DMSO)(18)(H(2)O)(6)].(DMSO)(6)(EtOH)(6)(H(2)O)(
      6) (1.guests, ip = isophthalate) and
      [Ni(24)(OH)(12)(SO(4))(12)(ip)(6)(DMSO)(12)(H(2)O)(12)].(DMSO)(6)(EtOH)(6)(H(2)O)
      20) (2.guests), constructed with nanosized tetraicosanuclear Co(II) and Ni(II)
      wheels are solvothermally synthesized. Both complexes show intra- and interwheel
      dominant antiferromagnetic interactions.

PMID- 22626500
TI  - Mesenchymal stem cells and prostaglandins may be critical for intestinal wound
      repair.

PMID- 22626501
TI  - Dead on arrival: understanding the failure of CTLA4-immunoglobulin therapy in
      inflammatory bowel disease.

PMID- 22626502
TI  - Microparticles and paracrine signaling in portal hypertension: crucial
      conversations or idle chat?

PMID- 22626503
TI  - How can we improve quality of care for patients with cirrhosis?

PMID- 22626504
TI  - Cutaneous vasculitis in ulcerative colitis mimicking Henoch-Schonlein purpura.
AB  - To the best of our knowledge, no cases of ulcerative colitis (UC) mimicking
      Henoch-Schonlein purpura (HSP) have been reported so far. During a 28-year period
      5635 patients were followed up at our Pediatric Rheumatology Unit and 357 had HSP
      according to the European League Against Rheumatism, the Paediatric Rheumatology
      International Trials Organisation and the Paediatric Rheumatology European
      Society validated classification criteria. At the same period, 148 patients with
      IBD according to the European Society for Paediatric Gastroenterology, Hepatology
      and Nutrition criteria were followed up at the Pediatric Gastroenterology Unit in
      our University Hospital. Only two of them had vasculitis, as an extra intestinal
      manifestation of UC mimicking HSP, and fulfilled both disease criteria. A 2-year
      old girl had bloody diarrhoea, severe abdominal pain, arthritis in ankles,
      petechiae and palpable purpura not related to thrombocytopenia in lower limbs. A
      5-year old boy had bloody diarrhoea, palpable purpura in buttocks, lower limbs,
      penis and scrotum associated with arthritis in knees, orchitis in right testicle
      and periarticular swelling in hands and feet. Their ileocolonoscopy showed
      diffuse mucosal erythema, oedema, friability and multiple irregular ulcers, and
      histopathological examination of colonic specimen revealed diffuse chronic
      mucosal inflammation, crypt distortion and crypt abscesses suggesting ulcerative
      colitis. There were no signs of intestinal vasculitis in both cases. In
      conclusion, this is the first study in a paediatric population that evidenced
      palpable purpura associated with UC mimicking HSP.

PMID- 22626505
TI  - Listeria infection in patients on anti-TNF treatment: report of two cases and
      review of the literature.
AB  - Listeria monocytogenes is an aerobic gram positive intracellular bacillus,
      predominantly affecting pregnant women, immunocompromised patients and old
      individuals. Invasive listeriosis, meningitis and meningoencephalitis,
      bacteraemia with or without joint, eye or heart focalization are clinical
      manifestations of the disease. Anti-TNF-alpha drugs blocking the host's response
      against various microorganisms, particularly intracellular agents like Listeria
      monocytogenes, increase the risk of disease. We report two cases of L.
      monocytogenes meningitis in ulcerative colitis patients under infliximab plus
      steroids. One patient is HIV-1 infected. A review of reported invasive
      listeriosis cases under anti-TNF drugs is also showed.

PMID- 22626506
TI  - Urinary NMR metabolomic profiles discriminate inflammatory bowel disease from
      healthy.
AB  - BACKGROUND AND AIMS: Inflammatory bowel disease, a chronic inflammation of the
      intestinal tract, presents in two variations, Ulcerative Colitis (UC) and Crohn's
      disease (CD). Given that treatment of CD differs from UC, a single test that
      provided strong diagnostic ability would offer great clinical value. Two previous
      studies have indicated that CD can be distinguished from UC, and that both can be
      distinguished from non-IBD-type gastrointestinal disease, based on urinary and
      faecal metabolite profiling. METHODS: Analysis of healthy as well as CD and UC
      patients attending an IBD clinic was performed. IBD patients were classified into
      two groups (CD or UC) based on chart review of clinical, endoscopic, and
      histological assessment. Urine samples were obtained and analyzed using nuclear
      magnetic resonance (NMR) spectroscopy combined with targeted profiling
      techniques, followed by univariate and multivariate statistical analysis.
      RESULTS: Based on urinary metabolomics, individuals with IBD could be
      differentiated from healthy. Major differences between IBD and healthy included
      TCA cycle intermediates, amino acids, and gut microflora metabolites. Comparison
      of CD and UC patients revealed discrimination, but removal of patients with the
      surgical intervention confounder revealed that CD could not be discriminated from
      UC. CONCLUSIONS: This study highlights the potential for metabolomics to
      distinguish IBD from the healthy state but shows that careful consideration must
      be given to establishing disease-representative cohorts that are free of
      confounding factors.

PMID- 22626507
TI  - High smoking cessation rate in Crohn's disease patients after physician advice-
      the TABACROHN Study.
AB  - INTRODUCTION: Tobacco smoking has a significant impact on the development of
      Crohn's disease (CD) and its clinical course, making smoking cessation one of the
      main goals in CD therapeutic strategy. AIMS: To evaluate the effectiveness of an
      advice-based smoking cessation strategy among CD patients. METHODS: We have
      performed a prospective multicenter study which enrolled 408 CD smokers. At
      inclusion all patients were instructed about the risks of smoking and
      subsequently followed every 3 months. Each center used additional smoking
      cessation strategies based on available resources. Urinary cotinine and exhaled
      carbon monoxide levels were evaluated in a subgroup of patients. RESULTS: Median
      study follow up was 18 months. 31% of the patients achieved complete smoking
      cessation and 23% were smoking-free at the end of their follow up with 8% of
      smoking relapse. Most patients not achieving smoking cessation did not change
      their smoking habit with only 5% presenting a decrease in tobacco load. 63% of
      patients willing to quit smoking received help from another specialist, most
      frequently the pulmonologist (47%). Surprisingly, most patients (88%) tried to
      quit smoking with no pharmacological therapy and bupropion, varenicline and
      nicotine replacement treatment were used in few patients. Urinary cotinine and
      exhaled CO levels tested in a subgroup of patients proved to have a good
      correlation with the self-reported smoking habit. No predictors of successful
      smoking cessation were identified. CONCLUSION: Our results underline that an anti
      tobacco strategy mostly based on CD patients's education and counseling is
      feasible and effective in helping patients reach complete abstinence.

PMID- 22626508
TI  - Economic impact of combination therapy with infliximab plus azathioprine for drug
      refractory Crohn's disease: a cost-effectiveness analysis.
AB  - BACKGROUND: Combination therapy with infliximab (IFX) and azathioprine (AZA) is
      significantly more effective for treatment of active Crohn's disease (CD) than
      IFX monotherapy. However, AZA is associated with an increased risk of lymphoma in
      patients with inflammatory bowel disease. AIM: To evaluate the cost-effectiveness
      of combination therapy with IFX plus AZA for drug-refractory CD. METHODS: A
      decision analysis model is constructed to compare, over a time horizon of 1year,
      the cost-effectiveness of combination therapy with IFX plus AZA and that of IFX
      monotherapy for CD patients refractory to conventional non-anti-TNF-alpha
      therapy. The treatment efficacy, adverse effects, quality-of-life scores, and
      treatment costs are derived from published data. One-way and probabilistic
      sensitivity analyses are performed to estimate the uncertainty in the results.
      RESULTS: The incremental cost-effectiveness ratio (ICER) of combination therapy
      with IFX plus AZA is 24,917 GBP/QALY when compared with IFX monotherapy. The
      sensitivity analyses reveal that the utility score of nonresponding active
      disease has the strongest influence on the cost-effectiveness, with ICERs ranging
      from 17,147 to 45,564 GBP/QALY. Assuming that policy makers are willing to pay
      30,000 GBP/QALY, the probability that combination therapy with IFX plus AZA is
      cost-effective is 0.750. CONCLUSIONS: Combination therapy with IFX plus AZA
      appears to be a cost-effective treatment for drug-refractory CD when compared
      with IFX monotherapy. Furthermore, the additional lymphoma risk of combination
      therapy has little significance on its cost-effectiveness.

PMID- 22626509
TI  - Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007
      2008.
AB  - PURPOSE: The objective of this study was to estimate the latest prevalence of
      major comorbidities associated with gout and hyperuricemia in the US based on a
      recent, nationally representative sample of US men and women. METHODS: Using data
      from 5707 participants aged 20 years and older in the National Health and
      Nutrition Examination Survey 2007-2008, we calculated the national prevalence and
      population estimates of major comorbidities according to gout status and various
      hyperuricemia levels, compared with those without these conditions. Case
      definitions of gout and comorbidities were based on an affirmative answer to a
      question that asked whether a physician or a health professional had diagnosed
      the corresponding condition. RESULTS: Among these individuals with gout, 74% (6.1
      million) had hypertension, 71% (5.5 million) had chronic kidney disease stage
      >=2, 53% (4.3 million) were obese, 26% (2.1 million) had diabetes, 24% (2.0
      million) had nephrolithiasis, 14% (1.2 million) had myocardial infarction, 11%
      (0.9 million) had heart failure, and 10% (0.9 million) had suffered a stroke.
      These proportions were substantially higher than those among individuals without
      gout (all P-values <.67). With increasing levels of hyperuricemia, there were
      graded increases in the prevalences of these comorbidities. In the top category
      (serum urate >=10 mg/dL), 86% of subjects had chronic kidney disease stage >=2,
      66% had hypertension, 65% were obese, 33% had heart failure, 33% had diabetes,
      23% had myocardial infarction, and 12% had stroke. These prevalences were 3-33
      times higher than those in the lowest serum urate category (<4 mg/dL). Sex
      specific odds ratios tended to be larger among women than men, and the overall
      comorbidity prevalence was highest among individuals with both gout and
      hyperuricemia. CONCLUSIONS: These findings from the latest nationally
      representative data highlight remarkable prevalences and population estimates of
      comorbidities of gout and hyperuricemia in the US. Appropriate preventive and
      management measures of these comorbidities should be implemented in gout
      management, with a preference to strategies that can improve gout and
      comorbidities together.

PMID- 22626511
TI  - The equine intestinal microbiome.
AB  - The equine intestinal tract contains a complex microbial population (microbiota)
      that plays an important role in health and disease. Despite the undeniable
      importance of a 'normal' microbiota, understanding of the composition and
      function of this population is currently limited. As methods to characterize the
      microbiota and its genetic makeup (the microbiome) have evolved, the composition
      and complexity of this population are starting to be revealed. As is befitting a
      hindgut fermenter, members of the Firmicutes phylum appear to predominate, yet
      there are significant populations of numerous other phyla. The microbiome appears
      to be profoundly altered in certain disease states, and better understanding of
      these alterations may offer hope for novel preventive and therapeutic measures.
      The development and increasing availability of next generation sequencing and
      bioinformatics methods offer a revolution in microbiome evaluation and it is
      likely that significant advances will be made in the near future. Yet, proper use
      of these methods requires further study of basic aspects such as optimal testing
      protocols, the relationship of the fecal microbiome to more proximal locations
      where disease occurs, normal intra- and inter-horse variation, seasonal
      variation, and similar factors.

PMID- 22626510
TI  - Awareness of kidney disease and relationship to end-stage renal disease and
      mortality.
AB  - BACKGROUND: Often, patients with chronic kidney disease are reported to be
      unaware of it. We prospectively evaluated the association between awareness of
      kidney disease to end-stage renal disease and mortality. METHODS: We utilized
      2000-2009 data from the National Kidney Foundation's Kidney Early Evaluation
      Program. Mortality was determined by cross reference to the Social Security
      Administration Death Master File and development of end stage by cross reference
      with the United States Renal Data System. RESULTS: Of 109,285 participants,
      28,244 (26%) had chronic kidney disease defined by albuminuria or estimated
      glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). Only 9% (n=2660) reported
      being aware of kidney disease. Compared with those who were not aware,
      participants aware of chronic kidney disease had lower eGFR (49 vs 62 mL/min/1.73
      m(2)) and a higher prevalence of albuminuria (52% vs. 46%), diabetes (47% vs
      42%), cardiovascular disease (43% vs 28%), and cancer (23% vs 14%). Over 8.5
      years of follow-up, aware participants compared with those unaware had a lower
      rate of survival for end stage (83% and 96%) and mortality (78% vs 81%), P <.001.
      After adjustment for demographics, socioeconomic factors, comorbidity, and
      severity of kidney disease, aware participants continued to demonstrate an
      increased risk for end-stage renal disease (hazard ratio 1.37; 95% confidence
      interval, 1.07-1.75; P <.0123) and mortality (hazard ratio 1.27; 95% confidence
      interval, 1.07-1.52; P <.0077) relative to unaware participants with chronic
      kidney disease. CONCLUSIONS: Among patients identified as having chronic kidney
      disease at a health screening, only a small proportion had been made aware of
      their diagnosis previously by clinicians. This subgroup was at a
      disproportionately high risk for mortality and end-stage renal disease.

PMID- 22626512
TI  - Understanding right ventricular dysfunction and functional tricuspid
      regurgitation accompanying mitral valve disease.
AB  - OBJECTIVES: The study objective was to correlate the degree of tricuspid
      regurgitation with clinical indicators of right-sided heart failure and both
      qualitative and quantitative measures of right-sided heart morphology and
      function in patients with degenerative mitral valve disease. METHODS: From 2001
      to 2007, 1833 patients with degenerative mitral valve disease, structurally
      normal tricuspid valve, and no coronary artery disease underwent surgery. Right
      sided heart morphology (right ventricular base-to-apex length, tethering distance
      and area, and right atrial systolic area) and right ventricular function
      (tricuspid annular plane systolic excursion, myocardial performance index, and
      tricuspid valve annular shortening) were measured on preoperative transthoracic
      echocardiograms for 100 randomly selected patients from each of tricuspid
      regurgitation grades 0, 1+, and 2+, and for all 93 patients with tricuspid
      regurgitation grade 3+/4+. Multivariable regression was used to evaluate the
      association of left- and right-sided heart morphology and function with tricuspid
      regurgitation. RESULTS: Increasing tricuspid regurgitation grade was associated
      with higher right ventricular pressure (P < .0001), increased tethering distance
      (P = .008), larger right atrial size (P = .0002), and worsening right ventricular
      function, particularly when 3+/4+ tricuspid regurgitation was present. When
      tricuspid regurgitation was 3+/4+, both tricuspid annular plane systolic
      excursion and myocardial performance index were almost certainly abnormal.
      Changes in right-sided heart morphology and right ventricular dysfunction were
      synergistic in relation to severity of tricuspid regurgitation. CONCLUSIONS:
      Functional tricuspid regurgitation accompanying mitral valve disease is
      associated with proportional changes in right-sided heart morphology; however,
      severe tricuspid regurgitation is nearly always associated with right ventricular
      dysfunction, suggesting a synergistic relationship. Right ventricular dysfunction
      is likely as important as tricuspid regurgitation because it offers an
      explanation for the negative prognostic impact of tricuspid regurgitation and has
      implications for the clinical management of patients.

PMID- 22626513
TI  - Historical perspectives of The American Association for Thoracic Surgery: W.
      Gerald Austen.

PMID- 22626515
TI  - Drug delivery research in Europe.

PMID- 22626514
TI  - Inhibiting CXCL12 blocks fibrocyte migration and differentiation and attenuates
      bronchiolitis obliterans in a murine heterotopic tracheal transplant model.
AB  - OBJECTIVES: Fibrocytes are integral in the development of fibroproliferative
      disease after lung transplantation. Undifferentiated fibrocytes (CD45+anti
      collagen 1+CXCR4+) preferentially traffic by way of the CXCR4/CXCL12 axis and
      differentiate into smooth muscle actin-producing (CD45+CXCR4+alpha-smooth muscle
      actin+) cells. We postulated that an antibody directed against CXCL12 would
      attenuate fibrocyte migration and fibro-obliteration of heterotopic tracheal
      transplant allografts. METHODS: A total alloantigenic mismatch murine heterotopic
      tracheal transplant model of obliterative bronchiolitis was used. The mice were
      treated with either goat-anti-human CXCL12 F(ab')(2) or goat IgG F(ab')(2). Buffy
      coat, bone marrow, and trachea allografts were collected and analyzed using flow
      cytometry. Tracheal luminal obliteration was assessed using hematoxylin-eosin and
      Direct Red 80 collagen stain. RESULTS: Compared with the controls, the anti
      CXCL12-treated mice showed a significant decrease in tracheal allograft fibrocyte
      populations at 7 and 21 days after transplantation. Bone marrow and buffy coat
      aspirates showed the same trend at 7 days. In the anti-CXCL12-treated mice, there
      was a 35% decrease in luminal obliteration at 21 days (65% vs 100% obliterated;
      interquartile range, 38% vs 10%; P = .010) and decreased luminal collagen
      deposition at 21 and 28 days after transplantation (P = .042 and P = .012,
      respectively). CONCLUSIONS: Understanding the role of fibrocytes in airway
      fibrosis after lung transplantation could lead to a paradigm shift in treatment
      strategy. Anti-CXCL12 antibody afforded protection against infiltrating
      fibrocytes and reduced the deterioration of the tracheal allografts. Thus, the
      CXCR4/CXCL12 axis is a novel target for the treatment of fibro-obliteration after
      lung transplantation, and the quantification of fibrocyte populations could
      provide clinicians with a biomarker of fibrosis, allowing individualized drug
      therapy.

PMID- 22626516
TI  - Knockdown of a G protein-coupled receptor through efficient peptide-mediated
      siRNA delivery.
AB  - In recent years, therapeutic applications of siRNAs have come into the focus of
      pharmaceutical research owing to their potential to specifically regulate gene
      expression. However, oligonucleotides have to overcome a series of extracellular
      and intracellular barriers which is why delivery systems helping to overcome
      these barriers are desperately needed. A promising approach to transport nucleic
      acids beyond cellular membranes is the use of cell-penetrating peptides (CPPs),
      which are able to autonomously cross the plasma membrane. Recently, we
      synthesized branched derivatives of truncated human calcitonin (hCT) and
      identified them as efficient vehicles for non-covalent gene delivery. Here we
      describe two novel branched hCT-derivatives that are optimized for efficient
      intracellular delivery of siRNA by conjugation with either a fatty acid or an
      endosomolytic peptide sequence. As target we chose the human NPY Y1 receptor
      (NPY1R), which belongs to the family of G protein-coupled receptors and thus
      constitutes a model for complex therapeutic targets related to various disorders.
      For instance, knockdown of Y1 receptor expression offers a potential therapy for
      osteoporosis. We present a read-out system that allows for the quantitation of
      the induced knockdown of receptor expression on the protein as well as on the
      mRNA level. As a result of this study, we could show that the herein presented
      cell-penetrating peptides effectively transport siRNA into HEK-293 cells without
      inducing cytotoxicity and that the knockdown rates are comparable to those
      obtained by lipofection.

PMID- 22626517
TI  - Encephalitozoonosis in pharmacologically immunosuppressed mice.
AB  - Encephalitozoon cuniculi is a parasite that has been identified as a cause of
      opportunistic infections in immunocompromised individuals. This study was
      performed to evaluate E. cuniculi infection in pharmacologically immunosuppressed
      mice. Mice were immunosuppressed with cyclophosphamide (100mg/kg twice a week,
      IP) or cyclosporin (10mg/kg daily, IP) and inoculated with 10(7)E. cuniculi
      spores IP. The E. cuniculi spores were cultivated in MDCK cells. E. cuniculi
      identification was performed by light microscopy studies using Gram-Chromotrope,
      Hematoxylin-Eosin and Toluidine blue-fuchsin staining techniques, as well as by
      PCR at 15, 30 and 45 days post-inoculation (DPI). Cyclophosphamide
      immunosuppressed mice have greatly reduced amounts of CD8(+), CD4(+) and CD3(+) T
      cells and CD19(+) B cells. The cells from these mice were analyzed by FACS and
      showed acute disseminated and fatal encephalitozoonosis. Mice treated with
      ciclosporin, which is both antiparasitic and immunosuppressive, have a milder,
      chronic, non-lethal infection and showed a significant reduction only in CD3(+)
      and CD4(+) T cell numbers. Our results support the role of CD8(+) T cells in
      controlling infection by E. cuniculi and show that preventive measures are
      essential for preventing this zoonosis in individuals undergoing chemotherapy for
      cancer or other immunosuppressive therapies.

PMID- 22626518
TI  - Enhancement in therapeutic efficacy of miltefosine in combination with synthetic
      bacterial lipopeptide, Pam3Cys against experimental Visceral Leishmaniasis.
AB  - Existing drugs for visceral leishmaniasis (VL) are partially effective, toxic,
      having high cost and long term treatment. Their efficacies are also compromised
      due to suppression of immune function associated during the course of infection.
      Combination therapy including a potential and safe immunostimulant with lower
      doses of effective drug has proven as a significant approach which is more
      effective than immunotherapy or drug therapy alone. In the present study, we have
      used the combination of Pam3Cys (an in-built immunoadjuvant and TLR2 ligand) and
      miltefosine. Initially dose optimization of both the agents was carried out and
      after that, antileishmanial effect of their combination was evaluated. All
      experiments were done in BALB/c mouse model. The immunomodulatory role of Pam3Cys
      on the immune functions of the host receiving combination treatment was also
      determined using immunological and biochemical parameters viz. phagocytosis,
      Th1/Th2 cytokines and production of ROS, RNS and H(2)O(2). Combination group
      showed significant enhancement in parasitic inhibition as compared to groups
      receiving miltefosine and Pam3Cys separately. Enhanced production of Th1
      cytokines as well as ROS, RNS and H(2)O(2) was witnessed during the study of
      immunological alterations. Remarkable increase in phagocytosis index was also
      observed. Thus, the risk of development of drug resistance against miltefosine
      can be resolved through using low doses of it and Pam3Cys (single-dose) in
      combination and also provide a promising alternative for cure of leishmaniasis,
      with a pronounced transformation of the host immune response.

PMID- 22626519
TI  - Characterization of Schistosoma japonicum estrogen-related receptor beta like 1
      and immunogenicity analysis of the recombinant protein.
AB  - The estrogen-related receptor beta like 1 (EsRRBL1) is a sex hormone receptor.
      Here, we describe the cloning and expression of the EsRRBL1 gene from Schistosoma
      japonicum (SjEsRRBL1). Quantitative real time PCR (qPCR) and Western blot
      analysis revealed that SjEsRRBL1 was highly expressed in 14-, 18-, 23- and 28
      days-old schistosomes at the transcriptional and protein levels, when the
      schistosomes were undergoing early development of reproductive organs, male and
      female coupling, and egg-laying. qPCR also showed that schistosomula isolated
      from a S. japonicum-susceptible mouse host had 3- to 4-fold higher expression of
      SjEsRRBL1 than that from the S. japonicum non-permissive Microtus fortis host or
      the non-susceptible rat host. Moreover, SjEsRRBL1 expression was 2-fold higher in
      schistosomula from female mice than that from male mice. Western blot analysis
      revealed that rSjEsRRBL1 had good antigenicity. After immunization of BALB/c mice
      with recombinant (r)SjEsRRBL1, partial and significantly protective efficacy was
      observed in two independent trials (30.84% and 30.70% worm reduction; 35.39% and
      35.61% liver eggs reduction), as compared with the blank control group. An enzyme
      linked immunosorbent assay (ELISA) showed that mice vaccinated with rSjEsRRBL1
      produced increased levels of specific IgG, IFN-gamma and IL-4, but a reduced
      IgG1/IgG2a ratio, as compared to the adjuvant control group and the blank control
      group, suggesting that rSjEsRRBL1 vaccination could induce a mixed Th1/Th2
      response. The results suggested that SjEsRRBL1 might be a critical regulator of
      schistosome development and represent a promising vaccine target for
      schistosomiasis.

PMID- 22626520
TI  - Trypanosoma cruzi: effects of azadirachtin and ecdysone on the dynamic
      development in Rhodnius prolixus larvae.
AB  - The effects of azadirachtin and ecdysone on the Trypanosoma cruzi population in
      the Rhodnius prolixus gut were investigated. T. cruzi were rarely found in the
      gut compartments of azadirachtin-treated larvae. High parasite numbers were
      observed in the stomach of the control and ecdysone groups until 10 days after
      treatment and in the small intestine and rectum until 25 days after treatment.
      High percentages of round forms developed in the stomachs of all groups, whereas
      azadirachtin blocked the development of protozoan intermediate forms. This effect
      was counteracted by ecdysone therapy. In the small intestine and rectum,
      epimastigotes predominated for all groups, but more of their intermediates
      developed in the control and ecdysone groups. Azadirachtin supported the
      development of round forms and their intermediates into trypomastigotes. In the
      rectum, trypomastigotes did not develop in the azadirachtin group and developed
      much later after ecdysone therapy. The parallel between the effects of
      azadirachtin and ecdysone on the host and parasite development is discussed on
      the basis of the present results because ecdysone appears to act directly or
      indirectly in determining the synchronic development of T. cruzi forms from round
      to epimastigotes, but not metacyclic trypomastigotes, in the invertebrate vector.

PMID- 22626521
TI  - Fractionated stereotactic conformal radiotherapy for optic nerve sheath
      meningiomas.
AB  - AIMS: To assess visual outcome, tumour control and treatment-related morbidity in
      patients with optic nerve sheath meningiomas (ONSMs) treated with fractionated
      stereotactic radiotherapy (FSRT). PATIENTS AND METHODS: A retrospective analysis
      of 45 patients (13 men and 32 women, median age 46 years) with ONSMs (51 optic
      nerves involved) treated in a single institution between 1997 and 2010 was
      carried out. FSRT was delivered to a dose of 50 Gy in 30 or 33 fractions as
      primary treatment in 39 patients and after surgery in six patients. RESULTS: At a
      median follow-up of 30 months (range 1-13 years), the tumour control in 41
      evaluable patients (four were lost to follow-up) was 100% at 5 years with no
      subsequent local or distant recurrence. Of the 46 evaluable optic nerves treated,
      41 had residual vision (38 with impaired vision) before radiotherapy and five
      were blind in one eye. There was no recovery of vision in any of the blind eyes.
      Of 41 optic nerves with residual vision, 13 had improvement, 24 remained stable
      and four deteriorated; two patients (4%) developed radiation retinopathy. One
      patient developed a central retinal artery occlusion in the untreated eye 10
      years after treatment. CONCLUSION: FSRT is highly effective at controlling the
      growth of ONSMs with improvement or stabilisation of visual deficit in 89% of the
      optic nerves retaining some vision, albeit with a small risk of radiation-induced
      retinopathy. The results support the use of FSRT as an effective approach in the
      management of ONSM. The lack of functional benefit in patients with severe visual
      impairment would argue for earlier institution of treatment before complete
      visual loss is established.

PMID- 22626522
TI  - Definitive radiotherapy or chemoradiotherapy in the treatment of Merkel cell
      carcinoma.
AB  - AIMS: Merkel cell carcinoma (MCC) is a radiosensitive tumour. Radiotherapy has an
      important role in its treatment, including definitive management. This study
      aimed to determine the in-field control achieved with definitive radiotherapy or
      chemoradiotherapy (CRT) and to examine patterns of relapse. MATERIALS AND
      METHODS: Patients treated with definitive radiotherapy or CRT for biopsy
      confirmed MCC were identified from records of the Royal Prince Alfred Hospital
      and Melanoma Institute Australia. Definitive treatment was defined as treatment
      delivered to macroscopic or residual microscopic disease at the primary site or
      in regional nodes. Patients with distant metastatic disease at presentation and
      those treated electively or adjuvantly (i.e. after microscopically clear
      excision) were excluded. RESULTS: Of 26 patients treated with definitive
      radiotherapy (n = 18) or CRT (n = 8), 20 were disease free at last follow-up
      (median follow-up 23.5 months). Five of the six patients who recurred did so at
      distant sites, with two experiencing simultaneous in-field failure at treated
      nodal sites where there had been macroscopic disease at presentation. Eighty-nine
      per cent of all patients and 85% of those with macroscopic disease were free of
      in-field recurrence at 2 years. CONCLUSION: Definitive radiotherapy or CRT
      produces excellent in-field disease control in the treatment of primary and
      regionally metastatic MCC.

PMID- 22626523
TI  - [Triclocarban antibacterial activity on resistant staphylococci, streptococci,
      and enterococci].
AB  - Triclocarban is an antiseptic of the anilide family. Its antibacterial activity
      was re-assessed in vitro against various susceptible and antibiotic resistant
      staphylococcus, streptococcus, and enterococcus strains. The results of this
      study show that, in vitro, the effectiveness of triclocarban antibacterial is
      maintained at very low MICs ranging from 0.5 to 8 mg/L for the various resistant
      strains studied. Triclocarban remains still very effective for the treatment of
      either initially bacterial skin and mucosal infections, or skin and mucosal at
      risk of super infection.

PMID- 22626524
TI  - Education modifies the relation of vascular pathology to cognitive function:
      cognitive reserve in cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy.
AB  - A clinical impact of cognitive reserve (CR) has been demonstrated in Alzheimer's
      disease, whereas its role in vascular cognitive impairment (VCI) is largely
      unknown. In this study, we investigated the impact of CR in patients with
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL), a genetic variant of pure VCI. A total of 247
      NOTCH3 mutation carriers from a two-center study were investigated using detailed
      neuropsychological and neuroimaging protocols. CR was operationalized as years of
      formal education. Brain pathology was assessed by MRI using normalized brain
      volume and lacunar lesion volume as proxies. Multivariate analyses were done for
      each structural measure with scores of processing speed, executive function, and
      memory as dependent variables. Additional linear regression models were conducted
      with interaction terms for education * brain volume and education * lacunar
      lesion volume. Education had an independent impact on cognitive performance in
      subjects with mild and moderate degrees of brain pathology, whereas there was no
      significant influence of education on cognition in patients with severe MRI
      changes. This interaction was found for processing speed, the cognitive domain
      most impaired in our patients. Our findings demonstrate an interaction of
      education and brain pathology in regard to cognitive impairment: the effect of
      education seems most pronounced in early disease stages but may ultimately be
      overwhelmed by the pathological changes. The results extend the concept of CR to
      VCI.

PMID- 22626526
TI  - Retraction of "Pathological biochemistry of a-synucleinopathy" by Takeshi
      Iwatsubo, published online on 18 September 2007.

PMID- 22626525
TI  - Photochemical inactivation of chikungunya virus in plasma and platelets using the
      Mirasol pathogen reduction technology system.
AB  - BACKGROUND: Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that
      has been responsible for a number of large-scale epidemics as well as imported
      cases covering a wide geographical range. As a blood-borne virus capable of
      mounting a high-titer viremia in infected humans, CHIKV was included on a list of
      risk agents for transfusion and organ transplant by the AABB Transfusion
      Transmitted Diseases Committee. Therefore, we evaluated the ability of the
      Mirasol pathogen reduction technology (PRT) system (CaridianBCT Biotechnologies)
      to inactivate live virus in contaminated plasma and platelet (PLT) samples. STUDY
      DESIGN AND METHODS: Plasma, PLTs, and phosphate-buffered saline controls were
      spiked with CHIKV and treated with riboflavin and varying doses of ultraviolet
      (UV) light using the Mirasol PRT system. Samples were tested before and after
      treatment for cytotoxicity, interference, and virus titer by titration and
      quantitative real-time reverse transcription-polymerase chain reaction. RESULTS:
      A significant reduction in CHIKV titer of greater than 99% was recorded after
      treatment of plasma or PLTs with the Mirasol PRT system, and the titer reduction
      was directly proportional to the UV dose delivered to the samples. No
      cytotoxicity of interference was observed in any sample at any treatment dose.
      CONCLUSION: These data indicate that the Mirasol PRT system efficiently
      inactivated live CHIKV in plasma and PLTs and could therefore potentially be used
      to prevent CHIKV transmission through the blood supply.

PMID- 22626528
TI  - Establishment and optimization of a wheat germ cell-free protein synthesis system
      and its application in venom kallikrein.
AB  - Wheat germ cell-free protein synthesis systems have the potential to synthesize
      functional proteins safely and with high accuracy, but the poor energy supply and
      the instability of mRNA templates reduce the productivity of this system, which
      restricts its applications. In this report, phosphocreatine and pyruvate were
      added to the system to supply ATP as a secondary energy source. After comparing
      the protein yield, we found that phosphocreatine is more suitable for use in the
      wheat germ cell-free protein synthesis system. To stabilize the mRNA template,
      the plasmid vector, SP6 RNA polymerase, and Cu(2+) were optimized, and a wheat
      germ cell-free protein synthesis system with high yield and speed was
      established. When plasmid vector (30 ng/MUl), SP6 RNA polymerase (15 U),
      phosphocreatine (25 mM), and Cu(2+) (5 mM) were added to the system and incubated
      at 26 degrees C for 16 h, the yield of venom kallikrein increased from 0.13 to
      0.74 mg/ml. The specific activity of the recombinant protein was 1.3 U/mg, which
      is only slightly lower than the crude venom kallikrein (1.74 U/mg) due to the
      lack of the sugar chain. In this study, the yield of venom kallikrein was
      improved by optimizing the system, and a good foundation has been laid for
      industrial applications and for further studies.

PMID- 22626530
TI  - Possible dysregulation of cortical plasticity in auditory verbal hallucinations-A
      cortical thickness study in schizophrenia.
AB  - INTRODUCTION: Investigations of gray matter changes in relation with auditory
      verbal hallucinations (AVH) have reported conflicting results. Assuming that
      alterations in gray matter might be related to certain symptoms in schizophrenia
      this study aimed to investigate changes in cortical thickness specific to AVH. It
      was hypothesized that schizophrenia patients suffering from persistent AVH would
      show significant differences in cortical thickness in regions involved in
      language-production and perception when compared to schizophrenia patients which
      had never experienced any hallucinations. METHODS: Using cortical thickness
      analysis the present study investigated ten schizophrenic patients suffering from
      AVH, ten non-hallucinating schizophrenic patients, and ten healthy control
      subjects. Anatomical data were acquired on a 3 T MRI system, transformed into
      standard space and cortically aligned to investigate local differences in whole
      brain cortical thickness between the two patient groups. Based on this
      comparison, brain regions with alterations specific for the patients with AVH
      were identified and then used as regions of interest to compare both patient
      groups to the healthy subjects respectively. RESULTS: Hallucinating patients
      showed gray matter reductions in the dominant hemisphere predominantly in sensory
      language areas relevant for speech processing. Increased cortical thickness was
      found in regions related to self-monitoring. CONCLUSIONS: Gray matter reductions
      in chronic schizophrenic patients may be the sequel of synaptic derangement or
      disease-related deregulation of language circuits. In order to clarify the
      ambiguous information processing additional demands might be put on cortical
      structures responsible for self-monitoring processes leading to changes in
      cortical thickness in the sense of neural plasticity.

PMID- 22626531
TI  - Biomechanical and coherent phenomena in morphogenetic relaxation processes.
AB  - Biological forms can be studied independently of the principles of their
      actualization, which was demonstrated in the book of D'Arcy Thompson "On Growth
      and Form" (1917) and in the nomogenetic theories of evolution. However the
      principles of actualization of forms have to be established and they are not
      directly related to the genetic system, being the generic phenomena non-reducible
      to the formal language of the genome. It is suggested that for the description of
      morphogenesis the concept of conformational relaxation is just as important as
      for enzymatic catalysis. Long-term relaxation properties are provided by the
      cytoskeleton. Compared to a single protein molecule, the cytoskeletal structures
      allow conformational movements on longer distances and for longer duration that
      can generally lead to a hyper-restoration of the initial state with the increased
      tension triggering further morphogenetic events. During this prolonged
      relaxation, the cytoskeleton microtubules hold the coherent state characterized
      by ultraweak emission of photons. This allows non-local interactions and assembly
      similar to that demonstrated recently for self-coordinated operation of
      photosynthetic antennae. As a result, the spatiotemporal patterns are formed
      based on the optimality principles that are established via internal reflective
      activity of biological systems.

PMID- 22626529
TI  - Impulsivity in the general population: a national study.
AB  - OBJECTIVE: The construct of impulsivity is an important determinant of
      personality differences, psychiatric disorders, and associated risk-taking
      behaviors. Most existing knowledge about impulsivity comes from clinical samples.
      To date, no study has estimated the prevalence of impulsivity and examined its
      correlates in the general population. METHOD: We analyzed data from a large
      national sample of the United States population. Face-to-face surveys of 34 653
      adults aged 18 years and older residing in households were conducted during the
      2004-2005 period. Diagnoses of mood, anxiety, and drug disorders as well as
      personality disorders were based on the Alcohol Use Disorder and Associated
      Disabilities Interview Schedule-DSM-IV Version. RESULTS: Impulsivity was common
      (17% of the sample), particularly among males and younger individuals, and
      associated with a broad range of axis I and II disorders, particularly drug
      dependence, cluster B, dependent and schizotypal personality disorders, bipolar
      disorder and ADHD. It was associated with behavioral disinhibition, attention
      deficits, and lack of planning. Individuals with impulsivity were more likely to
      engage in behaviors that could be dangerous to themselves or others, including
      driving recklessly, starting fights, shoplifting, perpetrating domestic violence
      and trying to hurt or kill themselves. They were exposed to higher risk of
      lifetime trauma and to substantial physical and psychosocial impairment.
      CONCLUSION: Given the association of impulsivity with psychiatric disorders and
      multiple adverse events, there is a need to target impulsivity in prevention and
      treatment efforts.

PMID- 22626532
TI  - A mean field Ising model for cortical rotation in amphibian one-cell stage
      embryos.
AB  - We propose a new physical mechanism of cortical rotation generation in one-cell
      embryos of amphibians based on a phase transition in the ensemble of microtubules
      localized to the cortical region of the cell interior. Microtubules, protein
      polymers formed from tubulin heterodimers, are highly negatively charged, which
      results in strong electrostatic interactions over tens of nanometers, even in the
      presence of counterions that partially screen electrostatic interactions. A
      simplified model that offers a plausible representation of these effects is based
      on the Ising Hamiltonian, which has been robustly applied to explain a wide range
      of order-disorder transitions in physics, chemistry and other sciences. An Ising
      model phase transition, especially with the supercooperative flow alignment
      effect of global rotation of the cortex, provides an alternative to models of
      cortical rotation based on microtubule polymerization or motor molecules. Insofar
      as there is any reality to the concept that microtubules are involved in
      consciousness, we propose that cortical rotation in the one-cell embryo is a
      better place to look for the purported microtubule entanglement or coherence
      properties than the adult brain.

PMID- 22626533
TI  - A case of acute deep palmar ulnar neuropathy due to a ganglion after
      weightlifting diagnosed with short segmental study and diagnostic ultrasound.

PMID- 22626534
TI  - Fatal outcomes of pediatric patients with moyamoya disease associated with
      pulmonary arterial hypertension. Report of two cases.

PMID- 22626535
TI  - Intraradicular lumbar disc herniation in a rare localization: case report.

PMID- 22626537
TI  - [Borderline states of cardiovascular risk in a worker population and its
      motivation to cope with changes in the style of life].

PMID- 22626536
TI  - CCR9+ plasmacytoid dendritic cells in the small intestine suppress development of
      intestinal inflammation in mice.
AB  - Almost all mice lacking specific molecules associated with regulatory T cells or
      barrier function develop intestinal inflammation in the colon, but not in the
      small intestine (SI). Therefore, intestinal homeostasis of the SI may be tightly
      controlled by other mechanisms. To determine the role of CCR9(+) plasmacytoid
      dendritic cells (pDCs) in intestinal homeostasis of the SI we transferred
      CD4(+)CD45RB(high) T cells into ccr9(-/-)*rag-2(-/-) mice. We showed that CCL25,
      a counterpart chemokine for CCR9, is constitutively expressed in the SI but not
      the colon and spleen of rag-2(-/-) or ccr9(-/-)*rag-2(-/-) mice before or after
      transfer of CD4(+)CD45RB(high) T cells. The ccr9(-/-)*rag-2(-/-) mice did not
      develop spontaneous intestinal inflammation in the SI and colon. Mice of both
      genotype where CD4(+)CD45RB(high) T cells were transferred developed colitis.
      However, the ccr9(-/-)*rag-2(-/-) mice also developed ileitis with marked
      infiltration of Th1 cells. These results suggest that CCR9(+) pDCs are possibly
      small, regulatory, antigen-presenting cells of the intestine that suppress
      intestinal inflammation.

PMID- 22626540
TI  - Successful medical treatment of an orbital osteoma in a dog.
AB  - A 6-year-old neutered male German Shepherd-mixed breed with a 2-month history of
      bilateral conjunctival hyperemia, epiphora, and a firm, slowly progressive
      swelling of the medial canthal region of the left eye (OS) was examined.
      Ophthalmic examination OS revealed a firm and smooth mass, extending from the
      medial canthus toward the medial orbital wall. Indirect ophthalmoscopy revealed
      indentation of the nasal part OS, which corresponded to the position of the
      orbital mass. Orbital neoplastic diseases were the main differential
      considerations. Computerized tomography revealed a bony smooth orbital mass
      without bone destructive features. Biopsy was performed, and histologic features
      were suggestive of osteoma. Systemic nonsteroidal anti-inflammatory (NSAID) drugs
      resulted in complete mass regression and absence of clinical signs for 5 years
      following initial diagnosis. This report describes the first case of canine
      orbital osteoma, which was responsive to NSAIDs.

PMID- 22626541
TI  - Placental mitochondrial DNA content and particulate air pollution during in utero
      life.
AB  - BACKGROUND: Studies emphasize the importance of particulate matter (PM) in the
      formation of reactive oxygen species and inflammation. We hypothesized that these
      processes can influence mitochondrial function of the placenta and fetus.
      OBJECTIVE: We investigated the influence of PM10 exposure during pregnancy on the
      mitochondrial DNA content (mtDNA content) of the placenta and umbilical cord
      blood. METHODS: DNA was extracted from placental tissue (n = 174) and umbilical
      cord leukocytes (n = 176). Relative mtDNA copy numbers (i.e., mtDNA content) were
      determined by real-time polymerase chain reaction. Multiple regression models
      were used to link mtDNA content and in utero exposure to PM10 over various time
      windows during pregnancy. RESULTS: In multivariate-adjusted analysis, a 10-ug/m3
      increase in PM10 exposure during the last month of pregnancy was associated with
      a 16.1% decrease [95% confidence interval (CI): -25.2, -6.0%, p = 0.003] in
      placental mtDNA content. The corresponding effect size for average PM10 exposure
      during the third trimester was 17.4% (95% CI: -31.8, -0.1%, p = 0.05).
      Furthermore, we found that each doubling in residential distance to major roads
      was associated with an increase in placental mtDNA content of 4.0% (95% CI: 0.4,
      7.8%, p = 0.03). No association was found between cord blood mtDNA content and
      PM10 exposure. CONCLUSIONS: Prenatal PM10 exposure was associated with placental
      mitochondrial alterations, which may both reflect and intensify oxidative stress
      production. The potential health consequences of decreased placental mtDNA
      content in early life must be further elucidated.

PMID- 22626542
TI  - The dystrophin-glycoprotein complex in brain development and disease.
AB  - In addition to muscle disease, defects in processing and assembly of the
      dystrophin-glycoprotein complex (DGC) are associated with a spectrum of brain
      abnormalities ranging from mild cognitive impairment (MCI) to neuronal migration
      disorders. In brain, the DGC is involved in the organisation of GABA(A) receptors
      (GABA(A)Rs) and aquaporin-4 (AQP4)-containing protein complexes in neurons and
      glia, respectively. During development, defects in the glycosylation of alpha
      dystroglycan that impair its ability to interact with the extracellular matrix
      (ECM) are frequently associated with cobblestone lissencephaly and mental
      retardation. Furthermore, mutations in the gene encoding E-sarcoglycan (SGCE)
      cause the neurogenic movement disorder myoclonus dystonia syndrome. In this
      review, we describe recent progress in defining distinct roles for the DGC in
      neurons and glia.

PMID- 22626543
TI  - Origins of arousal: roles for medullary reticular neurons.
AB  - The existence of a primitive CNS function involved in the activation of all
      vertebrate behaviors, generalized arousal (GA), has been proposed. Here, we
      provide an overview of the neuroanatomical, neurophysiological and molecular
      properties of reticular neurons within the nucleus gigantocellularis (NGC) of the
      mammalian medulla, and propose that the properties of these neurons equip them to
      contribute powerfully to GA. We also explore the hypothesis that these neurons
      may have evolved from the Mauthner cell in the medulla of teleost fish, although
      NGC neurons have a wider range of action far beyond the specific escape network
      served by Mauthner cells. Understanding the neuronal circuits that control and
      regulate GA is central to understanding how motivated behaviors such as hunger,
      thirst and sexual behaviors arise.

PMID- 22626545
TI  - Excelsior Surgical Society Edward D Churchill Lecture. Changes in combat casualty
      care.
AB  - There have been many positive changes in combat casualty care since Desert Storm.
      The Air Force has made a major change and significant improvement in combat
      casualty care, which is aided by the United States Army and Navy. The current
      care is second to none, including rehabilitation. This improvement in care and
      outcomes is due to the dedication of the doctors, nurses, corpsmen, pilots, and
      the incredible support services that make it happen.

PMID- 22626546
TI  - Lean management in academic surgery.
AB  - BACKGROUND: Lean is a management system designed to enhance productivity by
      eliminating waste. Surgical practice offers many opportunities for improving
      efficiency. Our objective was to determine whether systematic implementation of
      lean thinking in an academic otolaryngology operating room improves efficiency
      and profitability and preserves team morale and educational opportunities. STUDY
      DESIGN: In an 18-month prospective quasi-experimental study, a multidisciplinary
      task force systematically implemented lean thinking within an otolaryngology
      operating room of an academic health system. Operating room turnover time and
      turnaround time were measured during a baseline period; an observer-effect period
      in which workers were made aware that their efficiency was being measured but
      before implementing lean changes; and an intervention period after redesign
      principles had been used. The impact on teamwork, morale, and surgical resident
      education were measured during the baseline and intervention periods through
      validated surveys. A profit model was applied to estimate the financial
      implications of the study. RESULTS: There was no difference between the baseline
      and observer-effect periods of the study for turnover time (p = 0.98) or
      turnaround time (p = 0.20). During the intervention period, the mean turnover
      time and turnaround time were significantly shorter than during the baseline
      period (29 vs 38 minutes; p < 0.001 and 69 vs 89 minutes; p < 0.001,
      respectively). The composite morale score suggested improved morale after
      implementation (p = 0.011). Educational metrics were unchanged before and after
      implementation. The annual opportunity revenue for the involved operating room is
      $330,000; when extrapolated throughout the operating rooms, lean thinking could
      create 6,500 hours of capacity annually. CONCLUSIONS: Application of lean
      management techniques to a single operating room and surgical service improved
      operating room efficiency and morale, sustained resident education, and can
      provide considerable financial gains when scaled to an entire academic surgical
      suite.

PMID- 22626544
TI  - Discovery of novel vitamin D receptor interacting proteins that modulate 1,25
      dihydroxyvitamin D3 signaling.
AB  - The nuclear vitamin D receptor (VDR) modulates gene transcription in 1,25
      dihydroxyvitamin D(3) (1,25D) target tissues such as kidney, intestine, and bone.
      VDR is also expressed in heart, and 1,25D deficiency may play a role in the
      acceleration of cardiovascular disease. Employing a yeast two-hybrid system and a
      human heart library, using both a 1,25D-independent and 1,25D-dependent screen,
      we discovered six candidate VDR interacting proteins (VIPs). These novel VIPs
      include CXXC5, FASTK, NR4A1, TPM2, MYL3 and XIRP1. Mammalian two-hybrid assays as
      well as GST pull-downs were used to confirm VIP-VDR interaction, and the
      combination of these two assays reveals that CXXC5, XIRP1, FASTK and NR4A1
      interactions with VDR may be modulated by 1,25D. The functional effects of these
      VIPs on 1,25D-mediated gene expression were explored in transcriptional assays
      employing three separate and distinct 1,25D-responsive element (VDRE)-driven
      luciferase reporter genes in transfected Caco-2 and HEK-293 cells, and in a C2C12
      myoblast line. FASTK and TPM2 activated expression in all cell line and promoter
      contexts, while CXXC5 and XIRP1 exhibited differing effects depending on the cell
      line and promoter employed, suggesting promoter and cell-specific effects of
      these unique VIPs on VDR signaling. Further evaluation of the interaction between
      CXXC5 and VDR revealed that CXXC5 acts in a dose-dependent manner to stimulate
      VDR-mediated transcription on select VDREs. Identification of novel heart VIPs
      and their influence on VDR activity may increase our understanding of how vitamin
      D impacts cardiac physiology and may facilitate development of VDR/VIP drug
      analogs to combat heart disease.

PMID- 22626547
TI  - Long-term effects of aspirin on colorectal cancer.

PMID- 22626549
TI  - Backtranslating clinical knowledge for use in cheminformatics--what is the
      potential?
AB  - 'From bench to bedside' is seeing a very strong focus in current Drug Discovery.
      However, often overlooked are the advantages that turn out if data is used 'from
      bedside to bench', the fact one can also make beneficial use of clinical
      information in early Drug Discovery. By leveraging the wealth of clinical data
      carried by each marketed drug, down to the level of a single person, one can gain
      a deep insight that can be leveraged in conjunction with chemical structure
      information and therefore within all kinds of cheminformatics analyses. This
      supports the design of drugs that better fit the requirements of a well-defined
      subpopulation. Within this contribution I am going to focus on the realm of
      cheminformatics applications and how this data can thereby used to better impact
      the decisions of medicinal chemists.

PMID- 22626550
TI  - Synthesis of novel Schiff base analogues of 4-amino-1,5-dimethyl-2-phenylpyrazol
      3-one and their evaluation for antioxidant and anti-inflammatory activity.
AB  - 4-Aminoantipyrine (4-amino-1,5-dimethyl-2-phenylpyrazole-3-one) and its analogues
      have been found to be compounds of interest for their anti-inflammatory,
      analgesic, antiviral, antipyretic, antirheumatic and antimicrobial activities. In
      the present study, Schiff base analogues of 4-aminoantipyrine were synthesized by
      the condensation reaction with substituted benzaldehydes and then evaluated for
      their antioxidant and anti-inflammatory activities. From among the synthesized
      compounds (3a-m, 4 and 5), 3 k and 3f exhibited the highest antioxidant activity
      followed by 3g, 3l, 3c, 3i, 5, 3m and 3h. The IC(50) values for compounds 3 k and
      3f were found to be 0.44 and 0.93 MUM, respectively, comparable to that of
      ascorbic acid (IC(50) 0.41 MUM), a standard antioxidant agent. From the
      comparisons between the hydroxylated and methoxylated compounds, the rank order
      of antioxidant activity for the products resulting from benzylidene phenyl ring
      substitution was 2,4,6-OH>3,4-OH>3-OMe-4-OH>3,5-OMe-4-OH>2,4-OH>3-Me-4-OMe>3,4
      OMe>4-OMe>4-OH. The structure-activity relationship study revealed that the
      position and nature of the substituted group on the benzylidene phenyl ring of
      the Schiff base analogues of 4-aminoantipyrine play an important role in their
      antioxidant activity. The anti-inflammatory activity of 3f, which also exhibited
      excellent antioxidant activity, was evaluated in terms of its inhibition of NO
      production, an inflammatory modulator, in LPS pretreated RAW 264.7 cells using
      the Griess method. We also examined whether or not this compound had effect on
      iNOS and COX-2 mRNA expression in RAW 264.7 cells. It was observed that compound
      3f significantly reduced NO production and inhibited LPS-stimulated iNOS and COX
      2 mRNA levels in a dose-dependent manner. Overall, 3f showed promising
      antioxidant and anti-inflammatory activities and may be used as the lead compound
      in a future study.

PMID- 22626551
TI  - Synthesis of Leubethanol derivatives and evaluation against Mycobacterium
      tuberculosis.
AB  - Twenty-five derivatives of the natural diterpene leubethanol, including several
      potential pro-drugs, with changes in the functionality of the aliphatic chain or
      modifications of the phenolic group, were synthesized and tested in vitro by the
      MABA technique for their activity against the H37Rv strain of Mycobacterium
      tuberculosis. Several compounds showed antimycobacterial potencies similar to
      that of the lead compound and two of them displayed higher selectivity indexes.

PMID- 22626552
TI  - Synthesis and SAR of 4-aminocyclopentapyrrolidines as N-type Ca2+ channel
      blockers with analgesic activity.
AB  - A novel 4-aminocyclopentapyrrolidine series of N-type Ca(2+) channel blockers
      have been discovered. Enantioselective synthesis of the 4
      aminocyclopentapyrrolidines was enabled using N-tert-butyl sulfinamide chemistry.
      SAR studies demonstrate selectivity over L-type Ca(2+) channels. N-type Ca(2+)
      channel blockade was confirmed using electrophysiological recording techniques.
      Compound 25 is an N-type Ca(2+) channel blocker that produces antinociception in
      inflammatory and nociceptive pain models without exhibiting cardiovascular or
      motor liabilities.

PMID- 22626555
TI  - PHD finger of the SUMO ligase Siz/PIAS family in rice reveals specific binding
      for methylated histone H3 at lysine 4 and arginine 2.
AB  - We determined the three-dimensional structure of the PHD finger of the rice
      Siz/PIAS-type SUMO ligase, OsSiz1, by NMR spectroscopy and investigated binding
      ability for a variety of methylated histone H3 tails, showing that OsSiz1-PHD
      primarily recognizes dimethylated Arg2 of the histone H3 and that methylations at
      Arg2 and Lys4 reveal synergy effect on binding to OsSiz1-PHD. The K4 cage of
      OsSiz1-PHD for trimethylated Lys4 of H3K4me3 was similar to that of the BPTF-PHD
      finger, while the R2 pocket for Arg2 was different. It is intriguing that the PHD
      module of Siz/PIAS plays an important role, with collaboration with the DNA
      binding domain SAP, in gene regulation through SUMOylation of a variety of
      effectors associated with the methylated arginine-riched chromatin domains.

PMID- 22626554
TI  - The human phosphatase interactome: An intricate family portrait.
AB  - The concerted activities of kinases and phosphatases modulate the phosphorylation
      levels of proteins, lipids and carbohydrates in eukaryotic cells. Despite
      considerable effort, we are still missing a holistic picture representing, at a
      proteome level, the functional relationships between kinases, phosphatases and
      their substrates. Here we focus on phosphatases and we review and integrate the
      available information that helps to place the members of the protein phosphatase
      superfamilies into the human protein interaction network. In addition we show how
      protein interaction domains and motifs, either covalently linked to the
      phosphatase domain or in regulatory/adaptor subunits, play a prominent role in
      substrate selection.

PMID- 22626556
TI  - Green tea: an effective synergist with anticancer drugs for tertiary cancer
      prevention.
AB  - Green tea is now an acknowledged cancer preventive in Japan. Based on evidence
      that colorectal adenomas and prostate cancer in humans have been prevented, we
      review here the concept that the combination of anticancer drugs with green tea
      catechin synergistically induces apoptosis of human cancer cells, inhibits tumor
      formation in mice, and enhances inhibition of tumor growth in xenograft mouse
      models. As a molecular mechanism by the combination, the induction of growth
      arrest and DNA damage-inducible 153 (GADD153, CHOP) gene expression is discussed
      in relation to death receptor 5 and TRAIL-apoptotic pathway. The combination of
      anticancer drugs with green tea could be a new cancer therapeutic strategy in
      humans.

PMID- 22626557
TI  - Differentiating benign from malignant thyroid nodules using micro ribonucleic
      acid amplification in residual cells obtained by fine needle aspiration biopsy.
AB  - BACKGROUND: Fine needle aspiration biopsy (FNAB) is the most commonly used
      diagnostic tool to differentiate benign from malignant thyroid nodules.
      Nevertheless, some FNAB cytology results are not definite. In such cases
      diagnostic thyroid lobectomy is performed with malignancy rate on final
      histopathology ranging at 15%-75%. The aim of this study was to improve on the
      accuracy of FNAB-based cytology by amplification of microRNAs (micro ribonucleic
      acids [miRs]) from the residual cells left in the FNAB needle after submission
      for cytology. METHODS: Residual cells were collected from the needle cup after
      FNAB cytology of 77 consecutive patients with thyroid nodules. miR-enriched RNA
      was extracted for all patients with cytology showing either follicular lesion or
      suspicion for malignancy (n=11). The expression of miR-21, -31, -146b, -187, 
      221, and -222 was determined using real-time polymerase chain reaction. Results
      were compared with final surgical histopathology. RESULTS: RNA was successfully
      extracted from all FNAB specimens. Five patients had FNAB cytology suspicious for
      malignancy. The miR panel was positive in all five (100%). Six patients had
      follicular lesions on FNAB. The miR panel was positive in three of four patients
      (75%) with confirmed malignancy and was negative in two of two (0%) patients with
      benign pathology results. This corresponded to a specificity of 100%, sensitivity
      of 88%, and accuracy of 90%. CONCLUSIONS: RNA extraction from FNAB residual cells
      is feasible, and a miR panel amplified from the extracted RNA seems like a
      promising diagnostic tool in this limited number of patients.

PMID- 22626559
TI  - Lipid peroxidation products in machine perfusion of older donor kidneys.
AB  - BACKGROUND: Owing to the shortage of donors, organs with an increased risk
      potential such as grafts recovered from expanded criteria donors are increasingly
      being used in transplants. Machine perfusion (MP) technology offers the
      possibility of determining the biomarkers in the perfusion solution so that
      conclusions might be drawn regarding the effectiveness of organ preservation and
      organ viability. METHODS: All kidneys from the MP arm of our multicenter,
      randomized, controlled trial of MP whose donors were aged 55 years or older were
      included in the present study. The biomarkers, total glutathione-S-transferase
      (GST), alpha-GST, and pi-GST and markers for lipid peroxidation and cell decay
      were determined in the MP perfusate and correlated with the outcomes after kidney
      transplantation. RESULTS: A total of 111 machine perfused kidneys were included
      in the present study. The mean donor age was 64.1 +/- 6.6 y. The average cold
      ischemic time was 13.8 +/- 5.3 h. Total GST, alpha-GST, and lipid peroxidation
      markers were significantly elevated at the end of MP. However, according to the
      multivariate analysis, only the lipid peroxidation markers were independent
      predictors of delayed graft function after transplantation. CONCLUSIONS: Our data
      suggest that routine determination of lipid peroxidation markers in the perfusate
      of expanded criteria donor kidneys can provide the opportunity to identify the
      kidneys that have sustained severe oxidative damage and should be excluded from
      transplantation. Additional analysis of a larger cohort with more primary
      nonfunction cases is needed to confirm these findings.

PMID- 22626560
TI  - Noncosmetic benefits of single-incision laparoscopic sigmoid colectomy for
      diverticular disease: a case-matched comparison with multiport laparoscopic
      technique.
AB  - BACKGROUND: Single-incision laparoscopic (SIL) colectomy has gained significant
      momentum with anticipated benefit of improved cosmesis. Feasibility and safety of
      SIL colectomy have been shown; however, benefits are not well defined. The
      purpose of this study is to directly compare outcomes of SIL sigmoid colectomy
      for diverticular disease with standard multiport laparoscopic (LAP) technique.
      METHODS: SIL sigmoid colectomy cases performed for diverticular disease between
      August 2009 and July 2011 were case matched for age, gender, body mass index,
      American Society of Anesthesiologists score, previous abdominal operation, and
      need to mobilize the splenic flexure and compared with an equal number of LAP
      cases. Data analyzed included operative time, estimated blood loss, procedure
      conversion, incision length, length of hospital stay (LOS), 30-d hospital
      readmission, and postoperative pain scores. RESULTS: Twenty patients were
      analyzed in each group with no significant differences found in the six case
      matching criteria. Operative time, conversions, estimated blood loss, surgical
      site infection, and hospital readmissions were similar. The mean incision length
      for both groups was 5cm (P=0.72). LOS was 3.7d for the SIL group, which was >1d
      shorter than that for the LAP group (5.0d; P<0.05). Pain score at post-anesthesia
      care unit discharge and total amount of narcotic pain medication delivered in the
      post-anesthesia care unit was significantly less in the SIL group (P<0.05), as
      was maximum visual analog scale pain score on postoperative day 1 and
      postoperative day 2 (P<=0.01). CONCLUSIONS: SIL sigmoid colectomy is associated
      with noncosmetic benefits, including a reduction in early postoperative pain and
      decreased LOS. These findings may be related to reduced abdominal wall trauma.

PMID- 22626558
TI  - Bile salts increase epithelial cell proliferation through HuR-induced c-Myc
      expression.
AB  - BACKGROUND: Bile salts increase intestinal mucosal proliferation through an
      increase in c-Myc, a transcription factor that controls the expression of
      numerous translation regulatory proteins. HuR is an RNA-binding protein that
      regulates translation of target mRNAs. RNA-binding proteins can control mRNA
      stability by binding to AU- and U-rich elements located in the 3'-untranslated
      regions (3'-UTRs) of target mRNAs. AIM: To determine how bile salt-induced c-Myc
      stimulates enterocyte proliferation. METHODS: Enterocyte proliferation was
      measured both in vivo using C57Bl6 mice and in vitro using IEC-6 cells after
      taurodeoxycholate (TDCA) supplementation. HuR and c-Myc protein expression was
      determined by immunoblot. c-Myc mRNA expression was determined by PCR. HuR
      expression was inhibited using specific small interfering RNA. HuR binding to c
      Myc mRNA was determined by immunoprecipitation. RESULTS: TDCA increased
      enterocyte proliferation in vivo and in vitro. TDCA stimulates translocation of
      HuR from the nucleus to the cytoplasm. Cytoplasmic HuR regulates c-Myc
      translation by HuR binding to the 3'-UTR of c-Myc mRNA. Increased TDCA-induced c
      Myc increases enterocyte proliferation. CONCLUSIONS: Bile salts have beneficial
      effects on the intestinal epithelial mucosa, which are important in maintaining
      intestinal mucosal integrity and function. These data further support an
      important beneficial role of bile salts in regulation of mucosal growth and
      repair. Decreased enterocyte exposure to luminal bile salts, as occurs during
      critical illness, liver failure, starvation, and intestinal injury, may have a
      detrimental effect on mucosal integrity.

PMID- 22626561
TI  - Discrepancies between capillary glucose measurements and traditional laboratory
      assessments in both shock and non-shock states after trauma.
AB  - INTRODUCTION: The purpose of this study was to analyze the accuracy of capillary
      blood glucose (CBG) against laboratory blood glucose (LBG) in critically ill
      trauma patients during the shock state. METHODS: All critically ill trauma
      patients admitted to the Surgical Intensive Care Unit at the Los Angeles County +
      University of Southern California Medical Center requiring blood glucose
      monitoring from January 2007 to December 2008 were included. Accuracy of CBG was
      compared against LBG during shock and non-shock states. Shock was defined as
      either systolic blood pressure <90 mm Hg or mean arterial pressure <70 mm Hg and
      the need for vasopressor therapy. The Bland-Altman method was used to determine
      the agreement between CBG and LBG during shock and non-shock states. CBG values
      were considered to disagree significantly with LBG values when the difference
      exceeded 15%. RESULTS: During the 2-y study period, a total of 1215 patients were
      admitted to the Surgical Intensive Care Unit. Overall, the mean age was 38.4 +/-
      20.9 y, 79.6% (967) were male, and 75.0% (911) sustained blunt trauma. A total of
      1935 paired samples of CBG and LBG were included in this analysis (367 during
      shock and 1568 during non-shock). During shock, the mean difference between CBG
      and LBG levels was 13.4 mg/dL (95% CI, -15.4 to 42.2 mg/dL), and the limits of
      agreement were -27.1 and 53.9 mg/dL. A total of 136 CBG values (37.1%) differed
      from the LBG values by more than 15%. During non-shock, the mean difference
      between CBG and LBG levels was 12.6 mg/dL (95% CI, -19.9 to 32.5 mg/dL), and the
      limits of agreement were -20.6 and 45.8 mg/dL. A total of 639 CGB values (40.8%)
      differed from the LBG values by more than 15%. Agreement was lowest among
      hypoglycemic readings in both shock and non-shock states. CONCLUSION: There is
      poor correlation between the capillary and laboratory glucose values in both
      shock and non-shock states.

PMID- 22626562
TI  - The role of white spot syndrome virus (WSSV) VP466 protein in shrimp antiviral
      phagocytosis.
AB  - Widespread evidence indicates that the structural proteins of virus play very
      important roles in virus-host interactions. However, the effect of viral proteins
      on host immunity has not been addressed. Our previous studies revealed that the
      host shrimp Rab6 (termed as PjRab previously), tropomyosin, beta-actin and the
      white spot syndrome virus (WSSV) envelope protein VP466 formed a complex. In this
      study, the VP466 protein was shown to be able to bind host Rab6 protein and
      increase its GTPase activity in vivo and vitro. Thus, VP466 could function as a
      GTPase-activating protein (GAP) of Rab6. In the VP466-Rab-actin pathway, the
      increase of the Rab6 activity induced rearrangements of the actin cytoskeleton,
      resulting in the formation of actin stress fibers which promoted the phagocytosis
      against virus. Therefore our findings revealed that a viral protein could be
      employed by host to initiate the host immunity, representing a novel molecular
      mechanism in the virus-host interaction. Our study would help to better
      understand the molecular events in immune response against virus infection in
      invertebrates.

PMID- 22626563
TI  - A 15 nucleotide deletion mutation in coding region of the RIG-I lowers grass carp
      (Ctenopharyngodon idella) resistance to grass carp reovirus.
AB  - RIG-I (Retinoic acid-inducible gene I) is a pivotal receptor that detects
      numerous RNA and DNA viruses and plays crucial roles in the induction of type I
      interferons. In the present study, a deletion mutation in CiRIG-I
      (Ctenopharyngodon idella RIG-I) coding region was detected, its association with
      resistance/susceptibility to grass carp reovirus (GCRV) was examined, and
      possible mechanism was analyzed. A 15-bp deletion mutation was found, and the
      mutation results in a deletion of five amino acids. To investigate the genotypes
      and alleles, the relevant PCR products were electrophoresed on 2.5% agarose gel.
      Three genotypes and two alleles were discovered. The general allele was named as
      A and the deletion mutation allele was named as B. The deletion mutation cancels
      a predicted phosphorylation site and changes the secondary structure and the
      probability of peroxisomal targeting signal 1 in CiRIG-I. To explore the
      correlation between these genotypes and the resistance of grass carp to GCRV, a
      challenge experiment was carried out. The cumulative mortality in genotype AA
      (40.70%) and AB (52.73%) was significantly lower than that in genotype BB
      (71.43%) (P = 0.032). The result demonstrated that genotype AA and AB were
      resistant to GCRV, while genotype BB was susceptible. The 15-bp deletion mutation
      lowers the resistance of grass carp to GCRV. This result might provide a
      potential genetic marker for further investigation of selective breeding of
      resistant grass carp to GCRV.

PMID- 22626564
TI  - Non-specific immune response and disease resistance induced by Siegesbeckia
      glabrescens against Vibrio parahaemolyticus in Epinephelus bruneus.
AB  - The immunomodulatory effect of Siegesbeckia glabrescens extract-supplementation
      diets on innate immune response and disease resistance of kelp grouper,
      Epinephelus bruneus against Vibrio parahaemolyticus at weeks 1, 2, and 4 is
      reported. The serum lysozyme activity was significantly enhanced with any
      enriched diet from weeks 1-4 when compared to control diet (0%). The alternative
      complement haemolytic activities significantly were enhanced with all enriched
      diets on weeks 2 and 4 whereas the cellular reactive oxygen species (ROS) was
      significantly enhanced only with 1.0% and 2.0% diets. The reactive nitrogen
      intermediate (RNI) value was significantly enhanced with any enriched diet on
      weeks 2 and 4, but on first week it did not differ from control. The
      myeloperoxidase (MPO) production significantly increased with 1.0% and 2.0% diets
      from second week onwards; with other enriched diets the increase manifested on
      fourth week; but during first week it did not vary from that of the control with
      any enriched diet. The protection in terms of cumulative mortality was the least
      being 25% and 20% when fed with 1.0% and 2.0% diets. The present results indicate
      that feeding kelp grouper with S. glabrescens extract enriched diet at 1.0% and
      2.0% levels significantly enhance the immunological parameters, increase the
      disease resistance and minimize the cumulative mortality in E. bruneus against V.
      parahaemolyticus.

PMID- 22626565
TI  - Development of a strand specific real-time RT-qPCR assay for the detection and
      quantitation of murine norovirus RNA.
AB  - Murine norovirus (MNV), currently the only norovirus that efficiently replicates
      in cell culture, is often used as a model system to understand the molecular
      mechanisms of norovirus replication. MNV is a single stranded positive sense RNA
      virus of the Caliciviridae family. Replication of MNV involves the synthesis of
      both full length genomic and sub-genomic RNAs. The replication of these RNAs
      involves the synthesis of negative strand intermediates. To understand the
      molecular mechanism of RNA replication and the role of viral and host factors in
      virus replication, it is necessary to quantify accurately both positive and
      negative sense RNA molecules of the viral RNA during replication. Increasingly,
      strand specific reverse transcription-quantitative PCR (RT-qPCR) is becoming the
      method of choice for this kind of quantitation. Many strategies have been
      developed to avoid the false priming property of reverse transcriptase and to
      amplify specifically one strand in the presence of excess opposite strand. In
      this report, a SYBR based, real time RT-qPCR assay was developed to detect and
      quantify specifically the negative and the positive sense RNAs of MNV genomic
      RNA. This assay is based on using a tagged RT primer containing a non-viral
      sequence at the 5' end of the viral strand specific sequence. This non-viral
      sequence is then used to amplify selectively the strand specific cDNA at the PCR
      stage. This assay can be used for a range of MNV strains including MNV-1 and 3,
      as these are now widely accepted for use in molecular studies. The specificity of
      this assay was determined by its ability to quantify one strand in the presence
      of up to 10(6) copies of competitor opposite sense RNA. Using this assay, the
      production of both strands of MNV-1 RNA was monitored during viral single step
      growth curve.

PMID- 22626566
TI  - Detection of rabies viral RNA by TaqMan real-time RT-PCR using non-neural
      specimens from dogs infected with rabies virus.
AB  - To determine the burden of rabies in developing countries, a reliable and
      accurate diagnostic test for the examination of the brains of animals is needed.
      Recently, the number of samples and carcasses submitted to rabies diagnostic
      units has been declining. Methods for obtaining tissues from different regions of
      the brain are even more difficult, and direct florescent antibody examination may
      fail if the samples decomposed. The spread of rabies virus to peripheral non
      nervous tissues starts early during the pre-clinical phase. It has been shown
      that saliva and skin biopsies taken at the neck and containing hair follicles can
      be used in the ante-mortem diagnosis of rabies in humans. Obtaining oral swab
      samples, whisker or hair follicles from the heads of canines is easy and
      practical and can be performed without special equipment. The objective of this
      study was to determine whether these non-neural specimens can be used for the
      detection of rabies viral RNA. The RNAs extracted from these specimens were
      tested using a real-time reverse transcriptase polymerase chain reaction (RT
      PCR). The sensitivity of the TaqMan real-time RT-PCR analysis using samples from
      dogs confirmed to be infected with rabies virus was 84.6% (55/65), 81.8% (54/66)
      and 66.7% (44/66) when using oral swab samples, extracted whisker follicles and
      extracted hair follicles; the specificity of all specimen types was 100%. The
      negative predictive values were 77.8%, 74.4% and 61.4%, respectively. Although
      the rate of positivity when combining the three non-neural specimen types was
      increased to 86.4%, this level of sensitivity was not sufficient to help
      physicians whether to administer post exposure prophylaxis. However, these oral
      swab and whisker specimens may serve to enhance epidemiological surveillance;
      such data will contribute in the planning of rabies control programs.

PMID- 22626567
TI  - WITHDRAWN: A real-time PCR approach based on SPF10 primers and the INNO-LiPA HPV
      Genotyping Extra assay for the detection and typing of human papillomavirus.
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- 22626569
TI  - Antenatal corticosteroids: too much of anything is bad?

PMID- 22626570
TI  - A clinical/translational perspective: can a developmental hormone play a role in
      the treatment of traumatic brain injury?
AB  - Despite decades of laboratory research and clinical trials, a safe and effective
      treatment for traumatic brain injury (TBI) has yet to be put into successful
      clinical use. I suggest that much of the problem can be attributed to a
      reductionist perspective and attendant research strategy directed to finding or
      designing drugs that target a single receptor mechanism, gene, or brain locus.
      This approach fails to address the complexity of TBI, which leads to a cascade of
      systemic toxic events in the brain and throughout the body that may persist over
      long periods of time. Attention is now turning to pleiotropic drugs: drugs that
      act on multiple genomic, proteomic and metabolic pathways to enhance
      morphological and functional outcomes after brain injury. Of the various agents
      now in clinical trials, the neurosteroid progesterone (PROG) is gaining attention
      despite the widespread assumption that it is "just a female hormone" with
      limited, if any, neuroprotective properties. This perspective should change. PROG
      is also a powerful developmental hormone that plays a critical role in protecting
      the fetus during gestation. I argue here that development, neuroprotection and
      cellular repair have a number of properties in common. I discuss evidence that
      PROG is pleiotropically neuroprotective and may be a useful therapeutic and
      neuroprotective agent for central nervous system injury and some
      neurodegenerative diseases.

PMID- 22626571
TI  - [Stereotactic radiotherapy for brain metastasis].
AB  - Stereotactic radiosurgery is now well implanted in the radiotherapy treatment
      tools of brain metastasis. The dose can be delivered in one or multiple sessions.
      Results seem equivalent. CT scan and MRI imaging are required to delineate and
      calculate dosimetry. Doses are variable according to the size of the metastases,
      localization, pathology or equipment. Stabilization or reduction of tumour size
      is the rules after stereotactic treatment. Impact in terms of overall survival is
      more difficult to apprehend because of the general context of the disease. Many
      questions remain unresolved, such as the usefulness of whole brain irradiation,
      adaptation of the treatment schedule to tumour pathophysiology, role of
      stereotactic treatment after surgery of metastases, etc.

PMID- 22626572
TI  - CT-guided conformal cryoablation for peripheral NSCLC: initial experience.
AB  - PURPOSE: To study the feasibility of CT-guided and monitored percutaneous
      conformal cryoablation of Non-Small Cell Lung Cancer for patients who are not
      suitable for surgical resection. MATERIALS AND METHOD: CT-guided percutaneous
      conformal cryoablation was performed on 46 patients with peripheral Non-Small
      Cell Lung Cancer. Patients with tumor sizes less than 3 cm in diameter were
      treated with double-needle clamping cryoablation, while the patients with 3-5 cm
      tumor sizes were treated with multiple-needle conformal cryoablation. CT was used
      to monitor the extent of cryoablation during the procedures. At month 1, 3, 6,
      12, and 24 post-procedure, enhanced CT scans and/or PET-CT scans were performed
      to evaluate the impact of the therapy. RESULTS: The average tumor CT values were
      32+/-10 HU and -21+/-8 HU before and after cryoablation, respectively. The
      largest diameters of the lesions at month 1, 3, 6, 12, and 24 post-procedure were
      2.63+/-0.56 cm, 1.93+/-0.51 cm, 1.55+/-0.39 cm, 1.43+/-0.40 cm, and 1.38+/-0.38
      cm, respectively, in patients with tumor diameter less than 3 cm, and 3.63+/-0.39
      cm, 2.98+/-0.31 cm, 2.62+/-0.32 cm, 2.54+/-0.34 cm, and 2.56+/-0.37 cm
      respectively in patients with the tumor diameters between 3 and 5 cm. At the 24th
      month, there were 36 cases of complete response (83.7%), 7 cases of partial
      response (16.3%), and no cases of stable disease or progressive disease. 3
      patients died due to multiple metastases. CONCLUSION: CT-guided percutaneous
      conformal cryoablation is a safe, effective, and minimally invasive therapeutic
      method for peripheral lung cancer.

PMID- 22626573
TI  - Which obesity index best correlates with prostate volume, prostate-specific
      antigen, and lower urinary tract symptoms?
AB  - OBJECTIVE: To determine which measurement variable, waist circumference (WC),
      body mass index (BMI), or waist-to-hip ratio (WHR) is most closely related to the
      prostate volume (PV), prostate-specific antigen (PSA), and lower urinary tract
      symptoms (LUTS). METHODS: Between January 2010 and September 2011, 1632
      consecutive ostensibly healthy Korean men aged 40-69 years who visited our clinic
      for a prostate checkup were enrolled into the study. Exclusion criteria included
      pyuria, history of lower urinary tract disorder influencing urination, and a high
      PSA level of >3.0 ng/mL. All men underwent a detailed clinical evaluation using
      the International Prostate Symptom Score (I-PSS) questionnaire. Anthropometric
      measurements were determined. Serum PSA, urinalysis, and transrectal ultrasound
      were also performed. RESULTS: Data from 1601 men were analyzed. The mean age was
      51.6 years, WC 83.7 cm, BMI 24.8 kg/m(2), PV 24.6 mL, and the mean PSA level was
      1.07 ng/mL. Using multivariate analysis, PV most positively associated with WC (P
      < .001), while PSA level had negatively associated with BMI (P = .036) and no
      significant association with WC or WHR was noted. There was no significant
      relationship between various obesity indexes and I-PSS. CONCLUSION: Our data
      showed that PV positively associated with central obesity, as represented by WC.
      In contrast, serum PSA negatively associated with BMI, which represented overall
      obesity (ie, hemodilution). Our data also suggested that obesity is not
      associated with lower urinary tract symptoms in Korean men.

PMID- 22626574
TI  - Association between pioglitazone and urothelial bladder cancer.
AB  - The U.S. Food and Drug Administration and the European Medicines Agency have
      recently informed the public of a potential impact of pioglitazone (Actos) use on
      bladder cancer incidence. These recommendations are based on 2 recent large
      published cohort studies indicating a possible association between pioglitazone
      use and bladder cancer development. Currently, there is no urology literature on
      this subject. We present the current literature reporting the association between
      pioglitazone and bladder cancer.

PMID- 22626575
TI  - Synthetic mesh in the surgical repair of pelvic organ prolapse: current status
      and future directions.
AB  - In light of the recent Food and Drug Administration public health notification
      regarding complications associated with transvaginally placed mesh for pelvic
      organ prolapse (POP) repair, we review recent literature to evaluate current
      outcomes and complication data, analyze the clinical need for mesh on the basis
      of genetic and biochemical etiologies of POP, and investigate trends of mesh use
      via an American Urological Association member survey. Mesh-based techniques show
      better anatomic results than traditional repair of anterior POP, but subjective
      outcomes are equivalent. Further research and Level I evidence are required
      before mesh-based repair of POP can be standardized. Adequate surgical training
      and patient selection should decrease complication rates.

PMID- 22626576
TI  - Characteristics and outcomes of tumors arising from the distal nephron.
AB  - OBJECTIVE: To compare the characteristics and predictors of cancer-specific
      survival (CSS) of 2 rare distal nephron tumors--medullary renal cell carcinoma
      (MRCC) and collecting duct carcinoma (CDC). METHODS: All cases of histologically
      verified MRCC and CDC reported to The Surveillance, Epidemiology and End Results
      (SEER) database between 1995 and 2007 were considered. A number of
      characteristics were compared by tumor histology. Subset analyses were performed
      for metastatic patients and those managed surgically. CSS was analyzed using Cox
      proportional hazard models. RESULTS: Overall, 21 cases of MRCC and 227 cases of
      CDC met the criteria for analysis. Patients with MRCC were younger (median 24 vs
      63 years, P < .001), more often black (71.4% vs 22.7%, P < .001), metastatic at
      presentation (71.4% vs 27.8%, P < .001), and less likely to undergo surgery
      (61.9% vs 85.6%, P = .015) compared with patients with CDC. Tumor size was
      similar between MRCC and CDC (median 6 vs 5 cm, P = .70). Median survival was 5
      months for MRCC and 30 months for CDC (P < .001). In metastatic MRCC and CDC
      patients, surgery predicted CSS (HR 4.61 and 2.24, both P <=.05) despite having
      larger primary tumors than those managed nonsurgically (median 7.5 vs 5.0 cm, P <
      .01). CONCLUSION: Patients with MRCC present younger, at a later stage, and are
      more often black than patients with CDC. The stage migration toward localized
      kidney cancer is not apparent for these tumors. Although both cancers have a poor
      prognosis, the clinical and survival characteristics are distinct. Patients
      selected for cytoreductive surgery have improved survival.

PMID- 22626577
TI  - Risk factors for new-onset overactive bladder in older subjects: results of the
      Fujiwara-kyo study.
AB  - OBJECTIVE: To evaluate the risk factors for new-onset overactive bladder (OAB) in
      older subjects. METHODS: The present study enrolled 4427 subjects aged >= 65
      years who had participated in the Fujiwara-kyo study. The prevalence of OAB at
      baseline and 1 year later was evaluated using the OAB symptom score
      questionnaire. The incidence and remission rate of OAB were calculated. We
      identified the risk factors for OAB by evaluating the difference in
      characteristics (including sex, age, body mass index, life style, comorbidities,
      depressive status, metabolic syndrome, and sum of voiding symptoms) between those
      with and without new-onset OAB. In addition, the independent risk factors were
      determined by multivariate analysis. RESULTS: Of the 4427 subjects, 3685
      completely replied to the self-administrated questionnaires at baseline and 1
      year later. The incidence and remission rate of OAB was 11.9% and 29.8%,
      respectively. The male/female ratio, sum of voiding symptoms, alcohol consumption
      and smoking, hypertension, and depressive status in subjects with new-onset OAB,
      were significantly greater than those in subjects without new-onset OAB. A
      multivariate analysis, including sex (odds ratio 2.0, P < .0001), sum of voiding
      symptoms (odds ratio 1.1, P < .0001), and depressive status (odds ratio 1.8, P <
      .0001) were independent factors for new-onset OAB in older subjects. CONCLUSION:
      The results of the present study have demonstrated that male sex, the sum of
      voiding symptoms, and depression were independent factors for new-onset OAB. It
      is necessary to determine whether the treatment of patients with voiding symptoms
      or depression controls for new-onset OAB.

PMID- 22626578
TI  - Adrenomedullin inhibits norepinephrine-induced contraction of rat seminal
      vesicle.
AB  - OBJECTIVE: To investigate the effect of adrenomedullin (ADM) on seminal vesicle
      smooth muscle contractions in the rat and the specific receptor involved. Whether
      it was dependent on the nitric oxidant pathway was also investigated. METHODS:
      The seminal vesicles from Sprague-Dawley rats aged 8-10 weeks were incubated in
      Kreb's solution. Using an organ bath technique, the contraction of the seminal
      vesicle in response to norepinephrine (NE) and ADM was recorded, in the presence
      or absence of an ADM receptor blocker (hADM22-52), a calcitonin-gene-related
      peptide (CGRP) receptor blocker (hCGRP8-37), and L-NG-nitroarginine methyl ester,
      an endothelial nitric oxide synthase inhibitor. The basal tone, amplitude, and
      frequency of contraction were measured after incubation with the drugs. RESULTS:
      The results showed that the contraction induced by NE was effectively inhibited
      by ADM. The basal tone, amplitude, and frequency all decreased. The ADM effects
      on the NE-induced increases in basal tone and amplitude were completely blocked
      by hCGRP8-37, the CGRP receptor antagonist, but were not abolished by L-NG
      nitroarginine methyl ester. CONCLUSION: The findings have demonstrated that in
      the seminal vesicle the inhibitory effect of ADM on NE-induced contraction was
      mediated by the CGRP receptor but not by nitric oxide production.

PMID- 22626579
TI  - RENAL nephrometry score predicts surgery type independent of individual surgeon's
      use of nephron-sparing surgery.
AB  - OBJECTIVE: To evaluate whether surgeon factors, such as training and experience,
      have a strong impact on selection of surgical approach for treating renal
      cancers. Nephron-sparing surgery (NSS) has become the reference standard for
      tumors that are amenable to such an approach. Tumor size and configuration are
      important predictors of usage of NSS. The RENAL nephrometry score (RNS) has been
      developed to standardize reporting of tumor complexity, but the performance of
      this method within individual surgeons' practices, particularly in the community
      based setting, has not been evaluated previously. METHODS: Clinical data and RNS
      were collected retrospectively for 300 cases performed by 5 different surgeons
      with varying NSS usage rates (31-74%). RESULTS: Mean RNS for patients undergoing
      NSS (6.0) and radical nephrectomy (RN) (9.3) differed significantly (P <.0001),
      as did tumor size (2.8 vs 6.3 cm, P <.0001). RNS was a better predictor of
      surgery type (R(2) = .55) than was tumor size (R(2) = .43) for all 5 surgeons. In
      univariable analysis, individual surgeon, surgery year, glomerular filtration
      rate, tumor size, RNS, and each RNS component predicted NSS vs RN (each P <.05).
      In multivariable analysis, surgeon, tumor size, exophytic amount, and nearness to
      collecting system were independent predictors of NSS usage (P <.001). CONCLUSION:
      Despite significant variation in NSS usage by individual surgeons at a community
      based health system, RNS appears to be valid for both low and high usage. With
      increasing usage of NSS worldwide, RNS appears to reflect current patterns and
      may inform future practice for surgeons of all backgrounds.

PMID- 22626580
TI  - Phase IIb, multicenter, double-blind, randomized, placebo-controlled, parallel
      group study to determine effects of elocalcitol in women with overactive bladder
      and idiopathic detrusor overactivity.
AB  - OBJECTIVE: To evaluate the efficacy and safety of elocalcitol in the treatment of
      women with overactive bladder and idiopathic detrusor overactivity. METHODS: The
      study was a multicenter, double-blind, randomized, placebo-controlled, parallel
      group trial of women with overactive bladder symptoms recruited from 48 European
      tertiary referral centers. The participants were randomized to receive either
      placebo or elocalcitol, 75 MUg/d or 150 MUg/d for 4 weeks. A 3-day bladder diary,
      the Urgency Perception Scale, the Patient's Perception of Bladder Condition, and
      urodynamics were used before and after treatment. Vital signs, laboratory blood
      tests, 24-hour urine collection, and electrocardiography were also performed to
      assess the safety. The analysis of covariance test was used to compare the
      treatment groups. The primary objective was to evaluate the change in bladder
      volume at the first involuntary detrusor contraction from baseline. RESULTS: A
      total of 308 women were studied. No significant change was seen in the urodynamic
      parameters between the placebo and elocalcitol groups, except for the bladder
      volume at the first desire to void. The frequency of incontinence episodes was
      significantly reduced in the elocalcitol group compared with the placebo group (P
      = .02). The Patient's Perception of Bladder Condition score improved
      significantly after treatment for the women receiving elocalcitol compared with
      those receiving placebo (P = .02). Treatment with both doses of elocalcitol was
      well tolerated, and no differences versus placebo were observed. CONCLUSION:
      Although the primary endpoint was not achieved, elocalcitol appears to be an
      effective and well-tolerated drug for the treatment of women with overactive
      bladder and idiopathic detrusor overactivity. However, the multicenter setting
      for the use of urodynamics might have biased the results of our study.

PMID- 22626581
TI  - Synchronous transperitoneal laparoscopic resection of right retroperitoneal
      schwannoma and left kidney monotypic PEComa in the presence of a duplicated
      inferior vena cava (IVC).
AB  - A 21-year-old female presented with a retroperitoneal mass in the right side and
      a centrally located renal mass in the left kidney with an aberrant vascular
      anatomy of a double inferior vena cava. The 2 tumors were radically excised by a
      transperitoneal laparoscopic approach in one session. Histopathologic examination
      revealed the right retroperitoneal lesion to be a schwannoma and the renal mass
      to be a cluster of monotypic neoplasms with perivascular epithelioid cell
      differentiation (PEComas). The latter is a rare tumor.

PMID- 22626582
TI  - Salvage laparoscopic radical prostatectomy following high-intensity focused
      ultrasound for treatment of prostate cancer.
AB  - OBJECTIVE: To test the feasibility and safety of salvage laparoscopic radical
      prostatectomy (sLRP) for recurrent prostate cancer after high-intensity focused
      ultrasound (HIFU) treatment. METHODS: Thirteen men (median age 61.3 years)
      fulfilled the criteria of recurrent prostate cancer after HIFU undergoing sLRP
      with HIFU performed using Ablatherm devices (EDAP TMS, Lyon, France). The median
      interval from primary treatment and biochemical recurrence was 38 months, and the
      median serum PSA nadir after primary therapy was 1.05 ng?mL. Perioperative data
      and functional outcome were recorded for each patient. Complications were
      recorded and graded according to Clavien scale. The prostatectomy specimens were
      analyzed for Gleason score, extracapsular extension, and surgical margins. Mean
      follow-up was 14 months. RESULTS: There was no perioperative mortality and no
      conversion to open surgery was necessary. Mean operation time was 220 minutes,
      mean blood loss was 150 mL, and none of the patients received any transfusion. On
      histopathologic evaluation, 8 patients had extracapsular extension (pT3a) and 5
      patients had intracapsular disease (pT2b). Positive surgical margins (PSMs) were
      detected in 2 patients in the pT3a group. Gleason score was 7 (3 + 4) in 6
      patients and (4 + 3) in 5 patients. Two patients had a Gleason score of 8. The
      median time to achieve continence was 6 months. Four patients showed mild
      incontinence and used 2 pads per day. None of the patients in our series were
      potent after sLRP. CONCLUSION: sLRP is feasible for men in whom HIFU has failed
      but has a higher morbidity rate than primary surgery.

PMID- 22626583
TI  - Comparison of two experimental models for urethral stricture in the anterior
      urethra of the male rabbit.
AB  - OBJECTIVE: To compare 2 urethral stricture models and determine the appropriate
      model for the generation of urethral stricture in rabbits. METHODS: A total of 28
      adult male New Zealand rabbits were included in the present study. They were
      separated randomly into 3 groups. Urethroscopy was performed using a pediatric
      resectoscope (13F). In 1 group (10 rabbits), circumferential electrocoagulation
      of the anterior urethra 2-3 mm long was performed until ulceration of the mucosa
      occurred. In the second group (10 rabbits), 2-3 mm wide resection from the
      anterior urethra was performed that was deep enough to expose the periurethral
      tissue to allow urine leakage from the lumen. The remaining 8 rabbits as the
      control group underwent only urethroscopy. On the 30th day, retrograde
      urethrography and urethroscopy were performed to evaluate urethral stricture
      formation. Histologic examination was done to evaluate the urethral pathologic
      changes. RESULTS: According to the urethrography and urethroscopy findings, no
      rabbits in the electrocoagulation or control group developed urethral stricture;
      however, significant stricture formation was observed in every case of the
      electroresection group. Regenerating urothelium at the luminal side of the
      urethra was seen in 6 rabbits in the electrocoagulation group and 4 showed normal
      urethra. In the electroresection group, extensive fibrosis that obstructed the
      urethral lumen and nodular collagen bundles in the urethral wall were seen.
      CONCLUSION: The electroresection method is more reliable than the
      electrocoagulation method in developing urethral stricture in the rabbit model. A
      2-3-mm-wide resection from the anterior urethra can successfully generate
      urethral stricture with respect to electrocoagulation. Electroresection offers an
      ideal animal model for generating urethral stricture.

PMID- 22626584
TI  - Assessing iodine intakes in pregnancy and strategies for improvement.
AB  - An adequate intake of iodine in the diet of pregnant women is important to ensure
      normal growth and development of the fetus. It is difficult, however, to
      accurately determine iodine intakes using traditional methods of dietary
      assessment, primarily because the contribution of iodised salt use, at the table
      and in cooking, to total iodine intake is difficult to quantify. Given the
      limitations of dietary assessment, biochemical indices in blood and urine are
      typically used to assess iodine status in children and adults. Although reference
      ranges exist for thyroid hormones, there has been no consensus on the cut-offs
      needed in pregnancy to diagnose iodine deficiency. In contrast, a median urinary
      iodine concentration (UIC) of 150-249 MUg/L has been established to determine the
      adequate iodine status of a group of pregnant women. However, the large intra
      individual variation in UIC from either spot or 24h urine samples means that UIC
      cannot be used to assess iodine status in an individual pregnant woman. The
      difficulty in determining if an individual pregnant woman is iodine deficient is
      problematic for cross-sectional studies examining associations between iodine
      status in pregnancy and developmental outcomes in the child.

PMID- 22626585
TI  - [Identification of occupational risks associated with diseases suspected to be of
      possible occupational origin seen in the National Health System].
AB  - In an earlier study, we identified 26 diseases of possible occupational origin,
      seen in different settings within the national health system in Catalonia. In
      this literature review we identify those occupational risk factors most strongly
      associated with these pathologies. After applying inclusion/exclusion criteria to
      754 reviews, meta-analyses and/or practice guidelines, 37 articles remained that
      were rated for study quality by 3 reviewers. Of these, the 31 studies of highest
      quality were examined in depth, and summarised in a final table. Ergonomic risk
      factors (manual handling of materials, highly repetitive movements and awkward
      postures), especially for musculoskeletal disorders of the upper extremity, and
      exposures to chemical products and physical agents, were prominent. These results
      provide an additional resource for primary care physicians to assist them with
      the identification of possible occupational illness and to improve communication
      between the National Health Service and social security system.

PMID- 22626586
TI  - Better rested, but more stressed? Evidence of the effects of resident work hour
      restrictions.
AB  - OBJECTIVE: After the publication of the 2009 Institute of Medicine report
      addressing resident sleep, the Accreditation Council for Graduate Medical
      Education implemented new work hour restrictions in 2011. We explored the effects
      of a resident schedule compliant with 2011 limits on resident sleep, fatigue,
      education, and aspects of professionalism. METHODS: Partially randomized cohort
      study of residents and hospitalist attendings on general pediatric inpatient
      teams at a large children's hospital. Five intervention group interns worked a
      shift-based schedule compliant with 2011 restrictions with a 12 hour maximum
      shift. Six control group interns maintained the existing every fourth night, 30
      hour call schedule. Interns kept daily work and sleep logs. Interns and
      attendings were surveyed regarding perceptions of education, professionalism, and
      overall well-being. RESULTS: The average amount of intern sleep per 24 hours did
      not differ between intervention and control groups (7.5 vs 7.3 hours; P = .63).
      However, intervention interns had a lower proportion of duty hours without any
      sleep in the preceding 24 hours compared to interns in the control group (1% vs
      15%; P < .001). Twenty-one of 22 survey items on perceptions of education and
      professionalism were rated lower in the intervention group with absolute
      differences ranging from 18% to 86% between the control and intervention groups,
      but only 5 items were statistically significant. CONCLUSION: Implementation of
      new duty hour restrictions should produce more rested interns at work. However,
      resident and faculty perceptions of education and professionalism may be
      adversely affected. The unexpected finding of increased work load compression may
      contribute to these outcomes.

PMID- 22626587
TI  - Impact of cystatin C and RIFLE on renal function assessment after cardiac
      surgery.
AB  - The lack of a consensus classification system and of a specific, sensitive, and
      early-stage biomarker for kidney injury frequently results in late diagnosis of
      acute kidney injury (AKI). The aim of the present study was to characterize the
      discriminatory power of cystatin C and the RIFLE and Acute Kidney Injury Network
      (AKIN) criteria for the assessment of renal dysfunction after cardiac surgery. A
      longitudinal, quantitative study was conducted in intensive care units of the
      Heart Institute (Sao Paulo, Brazil) in which 121 patients were followed for the
      first 72 hr after cardiac surgery. Most of the patients were male (61.2%), and
      the mean age was 50 years. The most frequent surgeries were valve replacement
      (48.8%) and myocardial revascularization (43.8%). AKI was defined as an increase
      of at least 50%, 0.3 mg/dl or 0.5 mg/dl in baseline serum creatinine. The
      percentage of participants meeting each of these criteria was 13.2%, 28.1%, and
      11.6%, respectively. A progressive increase in cystatin C levels was associated
      with a worsening of renal function, as classified by RIFLE and AKIN (p < .05).
      Analysis of the receiver operating characteristic (ROC) curves showed the RIFLE
      and AKIN classification to have good discriminatory power for the assessment of
      renal function, with the performance of cystatin C being poorer (area under the
      curve: 0.804 and 0.794 vs. 0.719). However, combining cystatin C and RIFLE
      resulted in greater discriminatory power for detecting kidney injury in
      postoperative patients than any marker in isolation.

PMID- 22626588
TI  - Molecular allergy diagnosis: we need to become more knowledgeable.

PMID- 22626589
TI  - The promise and obstacles of asthma genetics research.

PMID- 22626590
TI  - Immunologic disorders of the female and male reproductive tract.

PMID- 22626591
TI  - Enhanced nerve growth factor expression by mast cells does not differ
      significantly between idiopathic and allergic rhinitis.
AB  - BACKGROUND: The role of neurotrophins in allergic rhinitis (AR) has been well
      studied, but it has not been evaluated in idiopathic rhinitis (IR). OBJECTIVE: We
      aimed to evaluate the nasal beta-nerve growth factor (beta-NGF) expressions of
      mast cells in patients with AR and IR. METHODS: Seventeen patients with house
      dust mites-induced persistent moderate/severe allergic rhinitis (mean age: 29.7
      +/- 11.96), 14 patients with idiopathic rhinitis (mean age, 29.3 +/- 10.62), and
      16 healthy controls (29.9 +/- 11.57) were included in the study. Nasal biopsy
      specimens were taken from the posterior part of the inferior turbinate from all
      of the study subjects. Nasal beta-nerve growth factor and its receptors, pan
      neurotrophin receptor p75, and tyrosine kinase A (trkA) were assessed with an
      immunofluorescence assay. Mast cells were determined by both an
      immunofluorescence assay and immunohistochemistry as tryptase-positive cells.
      RESULTS: The beta-NGF, trkA, and p75 receptor counts were significantly higher in
      AR and IR patients than in the control group (P < .001, for each), but they were
      not different between AR and IR patients. Similarly, the ratio of beta-NGF+ mast
      cells/total mast cells and the ratio of beta-NGF+ mast cells/total beta-NGF+
      cells in AR and IR patients was found to be elevated when compared with the
      control group (P < .001, P < .001, P < .001, and P = .046, respectively);
      furthermore, the 2 ratios were not statistically different between the 2 patient
      groups. CONCLUSION: The increase in beta-NGF-expressing mast cells does not
      differ between idiopathic and allergic rhinitis. Therefore, we propose that mast
      cells do play a role in the pathogenesis of IR as important as in that of AR.

PMID- 22626592
TI  - 17q12-21 variants are associated with asthma and interact with active smoking in
      an adult population from the United Kingdom.
AB  - BACKGROUND: Although an association between 17q12-21 and asthma has been
      replicated across different populations, some inconsistencies have been found
      between different studies. OBJECTIVE: We investigated the association between
      genetic variation in this region with asthma, lung function, airway inflammation,
      hyperresponsiveness (AHR), and atopy in a case-control study of United Kingdom
      adults. The interaction between genotype and smoking was also evaluated. METHODS:
      Study subjects (n = 983) were carefully phenotyped using questionnaires,
      measurement of lung function, AHR (methacholine challenge), exhaled nitric oxide
      (eNO), and assessment of atopic status. Blood/saliva/buccal swabs were collected,
      and 47 single nucleotide polymorphisms (SNPs) in 17q12-21 were genotyped using
      MALDI-TOF (Matrix-assisted LASER desorption/ionisation-time of flight) mass
      spectrometry. We conducted a comprehensive investigation of 28 common SNPs within
      6 genes of interest (IKZF3, ZPBP2, ORMDL3, GSDMA, GSDMB, TOP2A). RESULTS: Sixteen
      SNPs were significantly associated with asthma after multiple testing correction
      (P <= .01), of which 5 (rs2290400, rs8079416, rs3894194, rs7212938, and
      rs3859192) were strongly associated (FDR P <= .0002), and one was novel (IKZF3
      rs1453559). For 3 of these SNPs, we found significant interaction with smoking
      and asthma (rs12936231, rs2290400, and rs8079416). Smoking modified the
      associations between 8 SNPs and lung function (rs9911688, rs9900538, rs1054609,
      rs8076131, rs3902025, rs3859192, rs11540720, and rs11650680). We observed
      significant interaction between 5 SNPs and smoking on AHR, and 3 interacted with
      smoking in relation to asthma with AHR (rs4795404, rs4795408, rs3859192).
      CONCLUSION: We found 1 novel association and replicated several previously
      reported associations between 17q12-21 polymorphisms and asthma. We demonstrated
      significant interactions between active smoking and polymorphisms in 17q12-21
      with asthma, lung function, and AHR in adults. Our data confirm that 17q12-21 is
      an important asthma susceptibility locus.

PMID- 22626593
TI  - Asthma deaths outside the hospital in an urban community from 2004 to 2008.
AB  - BACKGROUND: Several studies have been performed reviewing medical examiner's
      autopsy reports of asthma deaths. None, to our knowledge, have focused on the
      characteristics of asthma deaths in the urban community alone. OBJECTIVE: To
      characterize factors related to asthma deaths occurring outside the hospital
      setting in an urban community. METHODS: We reviewed the medical records of 22
      patients who died outside the hospital of asthma and underwent autopsy performed
      by the Milwaukee County medical examiner from 2004 to 2008. RESULTS: The mean age
      of the patients was 32 years (range, 12-71 years), 11 patients were male, and 14
      patients (64%) were African American. Seventeen patients (77%) died during the
      night or shortly on awakening. Twelve patients (55%) died in June, July, or
      August. A history of illicit drug, alcohol, or tobacco use was discovered in 13
      patients (59%). Toxicologic test results for drugs of abuse were positive in 4
      patients (18%). Twenty patients were using or overusing a short-acting beta
      agonist, 1 patient was taking omalizumab, and none were taking long-acting beta
      agonists alone. Two patients were taking no medications. Asthma severity and
      medication adherence were not consistently reported. Lung pathologic testing
      revealed eosinophils in 18 patients and a lack of neutrophils in every case.
      CONCLUSION: In this small and limited series of asthma deaths occurring in an
      urban setting outside the hospital, individuals were more likely to be African
      Americans, with deaths occurring more frequently at night, during the summer
      months, and in those with substance abuse and not taking anti-inflammatory asthma
      medications.

PMID- 22626594
TI  - Endotoxin exposure in inner-city schools and homes of children with asthma.
AB  - BACKGROUND: Endotoxins are stimulators of the immune system and, despite their
      potential to protect against allergy, have been associated with early wheezing
      and asthma morbidity. OBJECTIVE: To compare inner-city school endotoxin exposure
      with home endotoxin exposure in children with asthma. METHODS: Students with
      asthma were recruited from 12 urban elementary schools. Settled and airborne dust
      samples, linked to enrolled students, were collected from school classrooms,
      gymnasiums, and cafeterias twice during the academic year. For comparison,
      settled dust was collected once from the bedrooms of students with asthma.
      RESULTS: Two hundred twenty-nine school settled dust samples and 118 bedroom
      settled dust samples were collected and analyzed for endotoxin. The median
      endotoxin concentration for school samples was 13.4 EU/mg (range, 0.7-360.7
      EU/mg) and for home samples was 7.0 EU/mg (range = LLOD-843.0 EU/mg). The median
      concentration within each individual school varied from 6.6 EU/mg to 24.0 EU/mg.
      One hundred four students with asthma had matched classroom and bedroom endotoxin
      exposure measurements performed in the same season and demonstrated significantly
      higher concentrations of endotoxin in the students' classrooms (mean log value,
      1.13 vs 0.99, P = .04). The median of the classrooms was 12.5 EU/mg compared with
      their bedrooms, with a median of 7.0 EU/mg. Within the school environment, no
      significant difference was seen between the fall and spring samples (mean log
      value 1.14 vs 1.09; P = .35). CONCLUSION: Inner-city children with asthma were
      exposed to higher concentrations of endotoxin in their classrooms as compared
      with their bedrooms. Further studies are needed to evaluate school endotoxin
      exposure as a factor in asthma morbidity.

PMID- 22626595
TI  - Poor asthma control and exposure to traffic pollutants and obesity in older
      adults.
AB  - BACKGROUND: Environmental and host predictors of asthma control in older
      asthmatic patients (>65 years old) are poorly understood. OBJECTIVE: To examine
      the effects of residential exposure to traffic exhaust and other environmental
      and host predictors on asthma control in older adults. METHODS: One hundred four
      asthmatic patients 65 years of age or older from allergy and pulmonary clinics in
      greater Cincinnati, Ohio, completed the validated Asthma Control Questionnaire
      (ACQ), pulmonary function testing, and skin prick testing to 10 common
      aeroallergens. Patients had a physician's diagnosis of asthma, had significant
      reversibility in forced expiratory volume in 1 second or a positive methacholine
      challenge test result, and did not have chronic obstructive pulmonary disease.
      The mean daily residential exposure to elemental carbon attributable to traffic
      (ECAT) was estimated using a land-use regression model. Regression models were
      used to evaluate associations among independent variables, ACQ scores, and the
      number of asthma exacerbations, defined as acute worsening of asthma symptoms
      requiring prednisone use, in the past year. RESULTS: In the adjusted model, mean
      daily residential exposure to ECAT greater than 0.39 MUg/m(3) was significantly
      associated with poorer asthma control based on ACQ scores (adjusted beta = 2.85;
      95% confidence interval [CI], 0.58-5.12; P = .02). High ECAT levels were also
      significantly associated with increased risk of asthma exacerbations (adjusted
      odds ratio, 3.24; 95% CI, 1.01-10.37; P = .05). A significant association was
      found between higher body mass index and worse ACQ scores (adjusted beta = 1.15;
      95% CI, 0.53-1.76; P < .001). Atopic patients (skin prick test positive) had
      significantly better ACQ scores than nonatopic patients (adjusted beta = -0.39;
      95% CI, -0.67 to -0.11; P < .01). CONCLUSION: Higher mean daily residential
      exposure to traffic exhaust, obesity, and nonatopic status are associated with
      poorer asthma control among older asthmatic patients.

PMID- 22626596
TI  - Relationships between total and allergen-specific serum IgE concentrations and
      lung function in young adults.
AB  - BACKGROUND: Prior studies have shown relationships between serum immunoglobulin E
      (IgE) and asthma. OBJECTIVE: To investigate relationships between total and
      allergen-specific IgE concentrations and lung function in young adults. METHODS:
      Measurements of total IgE, allergen-specific IgE to 6 common allergens, and
      spirometry (forced expiratory volume in one second [FEV(1)], forced vital
      capacity [FVC], FEV(1)/FVC, and percent change in FEV(1) after bronchodilation)
      were used to calculate correlations between the logarithmically transformed IgE
      values and measures of lung function among participants in a birth cohort not
      selected for risk of allergic disease stratified by current asthma, prior asthma,
      or no asthma. RESULTS: The 428 participants were 51.6% female, 93% white, and
      18.4 (standard deviation = 0.6) years old. Forty-eight (11.2%) had current
      asthma, 55 (12.9%) had a history of asthma, and 325 (75.9%) never had asthma. For
      males with current asthma, correlations between total IgE and FEV(1)% and FVC%
      were -0.51 (P = .06) and -0.70 (P = .005), respectively. For females with current
      asthma, the only significant correlation was between total IgE and the FEV(1)/FVC
      ratio (-0.55, P = .001). After excluding smokers and individuals without
      detectable allergen-specific IgE, the negative correlations for both males and
      females remained statistically significant. The correlations among males or
      females with prior asthma or no history of asthma were minimal and not
      statistically significant. The sum of the allergen-specific IgEs showed the same
      pattern of relationships to lung function as did total IgE. CONCLUSION: Our
      results show significant negative correlations that vary by gender between both
      total and allergen-specific IgE and measurements of lung function in young adults
      with current asthma.

PMID- 22626597
TI  - Prevalence of atopic disorders and immunodeficiency in patients with ectodermal
      dysplasia syndromes.
AB  - BACKGROUND: Ectodermal dysplasia (ED) syndromes are a diverse group of disorders
      that affect multiple ectodermally derived tissues. Small studies and case reports
      suggest an increase in atopy and primary immunodeficiencies (PIDs) among patients
      with ED syndromes. OBJECTIVE: To determine the prevalence of clinical symptoms
      suggestive of atopy or immunodeficiency among a large cohort of children with ED
      syndromes. METHODS: A 9-page questionnaire was mailed to families who were
      members of the National Foundation for Ectodermal Dysplasias. The surveys were
      completed by parents of children younger than 18 years with a diagnosis of an ED
      syndrome or carrier state. Portions of the questionnaire were adapted from
      previously validated questionnaires developed by the International Study of
      Asthma and Allergies in Childhood (ISAAC). RESULTS: We received 347 completed
      questionnaires (41%). When compared with the 13- to 14-year-old children surveyed
      by ISAAC, we found both all-aged and age-matched children with ED syndromes,
      respectively, had significantly higher rates of asthma (32.2% and 37.2% vs
      16.4%), rhinitis symptoms (76.1% and 78.3% vs 38.9%), and eczema (58.9% and 48.9%
      vs 8.2%). The prevalence of physician-diagnosed food allergies (20.7%) and PIDs
      (6.1%) in these ED patients also exceeded known rates in the general pediatric
      population. CONCLUSION: This large-scale, retrospective study demonstrates a
      greater reported prevalence of symptoms suggestive of atopic disorders and PIDs
      among children with ED syndromes than the general pediatric population. A
      combination of genetic and environmental factors in ED syndromes may contribute
      to breaches of skin and mucosal barriers, permitting enhanced transmission and
      sensitization to irritants, allergens, and pathogens.

PMID- 22626598
TI  - Allergen stabilities and compatibilities in mixtures of high-protease fungal and
      insect extracts.
AB  - BACKGROUND: Current practice guidelines state that protease-rich fungal and
      insect extracts can be combined when preparing immunotherapy vaccines, but data
      supporting the stability of allergens in these mixtures have not been reported.
      OBJECTIVE: To determine the stabilities and compatibilities of Alternaria
      alternata and German cockroach allergens in mixtures with other high-protease
      fungal and insect (cockroach, imported fire ant) extracts at final extract
      concentrations consistent with injection dose targets for maintenance
      immunotherapy. METHODS: Mixtures containing Alternaria, German cockroach, and
      other fungal and insect extracts frequently included in immunotherapy vaccines
      were analyzed by a combination of quantitative analyses (enzyme-linked
      immunosorbent assays for multiallergen immunoglobulin E [IgE]-binding potency,
      major Alternaria allergen Alt a 1, and major German cockroach allergens Bla g 1
      and Bla g 2) and qualitative methods (immunoblotting). Mixtures and analogous
      single-extract controls containing 10 to 50% glycerin were evaluated after
      storage for up to 12 months at 2 degrees C to 8 degrees C. RESULTS: Mixtures of
      extracts within the same phylogenetic groups (fungal-fungal, insect-insect)
      retained favorable Alternaria and German cockroach allergen levels and activities
      under most conditions examined. For several cross-taxonomic (fungal-insect)
      extract combinations at 10 to 25% glycerin concentrations, different
      immunochemical test methods measuring single (major) or multiple allergens
      yielded threefold to 10-fold variations in allergen recoveries. CONCLUSION:
      Allergen compatibilities can be compromised in some fungal-insect extract
      mixtures, contrary to current immunotherapy practice parameter recommendations.
      Separation of these products into different treatment vials may be required to
      produce stable mixtures for subcutaneous immunotherapy. Data from assay
      methodologies with distinct binding specificities provide a critical assessment
      of allergen activities in high-protease extract mixtures.

PMID- 22626599
TI  - Outcome measures and serious asthma exacerbation in clinical trials of asthma
      controller medications.
AB  - BACKGROUND: With the introduction and approval of several new asthma controller
      medications for pediatric use, the risk-benefit ratio of these medications has
      not been fully evaluated. OBJECTIVE: To determine whether physiologic pulmonary
      measurements are superior to other measures in evaluating outcomes and to
      determine whether asthmatic children have a higher risk of serious adverse events
      than adults. METHODS: We obtained data on asthma controller medications approved
      between 1997 and 2010 from the US Food and Drug Administration archives. Six
      medications were approved for use in children and adults during this time. Of
      these, we were able to analyze 23 trials of 5 medications. Nine of the trials
      were conducted in pediatric patients and 14 in adults. RESULTS: We determined
      whether the primary outcome measure was a physiologic pulmonary measure or
      another measure and compared trial outcomes. We also evaluated serious adverse
      events, including mortality rates for both adult and pediatric trials. The
      frequency of successfully demonstrating efficacy was far superior using
      physiologic pulmonary measures (13/14 [93%]) compared with other outcome measures
      (4/9 [44%]). The frequency of serious asthma exacerbations, although less than
      1%, was higher in the pediatric group of patients (18/1,948 [0.9%]) compared with
      adults (4/2,460 [0.2%]), regardless of assignment to placebo or drug. CONCLUSION:
      These results suggest that physiologic pulmonary function measures should be used
      in evaluating the efficacy of asthma controller medications. These data also
      indicate that pediatric patients may be more prone to serious asthma
      exacerbations during clinical trials.

PMID- 22626600
TI  - Allergen immunotherapy practice patterns: a worldwide survey.
AB  - BACKGROUND: Allergists around the world have different practice styles when
      administering subcutaneous aeroallergen immunotherapy (IT) in peak pollen
      seasons, especially when changing doses or frequency of IT. The Immunotherapy
      practice parameters do not specifically address this issue. OBJECTIVE: Given the
      paucity of good data about adjustment of allergen immunotherapy during the pollen
      seasons, we examined whether a significant difference is present in the way
      allergists administer immunotherapy during allergy seasons. METHODS: To quantify
      the practice styles of allergists who are members of the American Academy of
      Allergy, Asthma and Immunology (AAAAI), a self-reported electronic survey was
      disseminated in September 2010 with the help of the AAAAI Needs Assessment
      Committee. The responses were tallied and analyzed according to demographic
      information. RESULTS: A total of 1,201 allergists in the AAAAI responded to the
      survey. Most responders practice in an urban or suburban nonacademic practice in
      the United States and have been in practice for more than 10 years. The size of
      their practice was variable. Those in practice for more than 10 years were more
      likely to adjust the dose and frequency of immunotherapy in pollen seasons.
      CONCLUSION: This survey highlights the differences in the practice styles of
      AAAAI member allergists, and these differences may be associated with their
      demographic characteristics. Given the wide variability in how allergists adjust
      dose and frequency of immunotherapy during pollen seasons, establishing
      guidelines regarding this routine dilemma might help standardize the delivery of
      treatment to patients.

PMID- 22626601
TI  - Treatment of idiopathic nonhistaminergic angioedema with bradykinin B2 receptor
      antagonist icatibant.

PMID- 22626602
TI  - Eutamias sibiricus: a new pet as a cause of asthma.

PMID- 22626603
TI  - Successful C1 esterase inhibitor therapy in a child with a novel type 3
      hereditary angioedema-like syndrome.

PMID- 22626604
TI  - Acute hemolysis secondary to high-dose intravenous immunoglobulin in a patient
      with Stevens-Johnson syndrome.

PMID- 22626605
TI  - Common variable immune deficiency and treatment with intravenous immunoglobulin
      during pregnancy.

PMID- 22626606
TI  - Graded challenge protocol for fluconazole hypersensitivity in a patient with
      cryptococcal pneumonitis.

PMID- 22626607
TI  - Allergen of the month--Stachybotrys chartarum.

PMID- 22626608
TI  - The cost effectiveness of radiofrequency ablation for Barrett's esophagus.
AB  - BACKGROUND & AIMS: Radiofrequency ablation (RFA) reduces the risk of esophageal
      adenocarcinoma (EAC) in patients with Barrett's esophagus (BE) with high-grade
      dysplasia (HGD), but its effects in patients without dysplasia are debatable. We
      analyzed the effectiveness and cost effectiveness of RFA for the management of
      BE. METHODS: We constructed a decision analytic Markov model. We conducted
      separate analyses of hypothetical cohorts of patients with BE with dysplasia (HGD
      or low-grade [LGD]) and without dysplasia. In the analysis of the group with HGD,
      we compared results of initial RFA with endoscopic surveillance with surgery when
      cancer was detected. In analyzing the group with LGD or no dysplasia, we compared
      3 strategies: endoscopic surveillance with surgery when cancer was detected (S1),
      endoscopic surveillance with RFA when HGD was detected (S2), and initial RFA
      followed by endoscopic surveillance (S3). RESULTS: Among patients with HGD,
      initial RFA was more effective and less costly than endoscopic surveillance.
      Among patients with LGD, when S3 was compared with S2, the incremental cost
      effectiveness ratio was $18,231/quality-adjusted life-year, assuming an annual
      rate of progression rate from LGD to EAC of 0.5%/year. For patients without
      dysplasia, S2 was more effective and less costly than S1. In a comparison of S3
      with S2, the incremental cost-effectiveness ratios were $205,500, $124,796, and
      $118,338/quality-adjusted life-year using annual rates of progression of no
      dysplasia to EAC of 0.12%, 0.33%, or 0.5% per year, respectively. CONCLUSIONS: By
      using updated data, initial RFA might not be cost effective for patients with BE
      without dysplasia, within the range of plausible rates of progression of BE to
      EAC, and be prohibitively expensive, from a policy perspective. RFA might be cost
      effective for confirmed and stable LGD. Initial RFA is more effective and less
      costly than endoscopic surveillance in HGD.

PMID- 22626609
TI  - Factors that predict response of patients with hepatitis C virus infection to
      boceprevir.
AB  - BACKGROUND & AIMS: Little is known about factors associated with a sustained
      virologic response (SVR) among patients with hepatitis C virus (HCV) infection to
      treatment with protease inhibitors. METHODS: Previously untreated patients (from
      the Serine Protease Inhibitor Therapy 2 [SPRINT-2] trial) and those who did not
      respond to prior therapy (from the Retreatment with HCV Serine Protease Inhibitor
      Boceprevir and PegIntron/Rebetol 2 [RESPOND-2] trial) received either a
      combination of peginterferon and ribavirin for 48 weeks or boceprevir,
      peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and
      ribavirin (total treatment duration, 28-48 wk). A good response to interferon was
      defined as a >= 1 log(10) decrease in HCV RNA at week 4; a poor response was
      defined as a <1 log(10) decrease. We used multivariate regression analyses to
      identify baseline factors of the host (including the polymorphism interleukin
      [IL]-28B rs12979860) associated with response. The polymorphism IL-28B rs8099917
      also was assessed. RESULTS: In the SPRINT-2 trial, factors that predicted a SVR
      to triple therapy included low viral load (odds ratio [OR], 11.6), IL-28B
      genotype (rs 12979860 CC vs TT and CT; ORs, 2.6 and 2.1, respectively), absence
      of cirrhosis (OR, 4.3), HCV subtype 1b (OR, 2.0), and non-black race (OR, 2.0).
      In the RESPOND-2 trial, the only factor significantly associated with a SVR was
      previous relapse, compared with previous nonresponse (OR, 2.6). Most patients
      with rs12979860 CC who received triple therapy had undetectable levels of HCV RNA
      by week 8 (76%-89%), and were eligible for shortened therapy. In both studies, IL
      28B rs12979860 CC was associated more strongly with a good response to interferon
      than other baseline factors; however, a >= 1 log(10) decrease in HCV-RNA level at
      week 4 was associated more strongly with SVR than IL-28B rs12979860. Combining
      the rs8099917 and rs12979860 genotypes does not increase the association with
      SVR. CONCLUSIONS: The CC polymorphism at IL-28B rs12979860 is associated with
      response to triple therapy and can identify candidates for shorter treatment
      durations. A >= 1 log(10) decrease in HCV RNA at week 4 of therapy is the
      strongest predictor of a SVR, regardless of polymorphisms in IL-28B.

PMID- 22626610
TI  - Chronic cadmium exposure in vitro causes acquisition of multiple tumor cell
      characteristics in human pancreatic epithelial cells.
AB  - BACKGROUND: Cancer may be a stem cell (SC)-based disease involving formation of
      cancer SCs (CSCs) potentially arising from transformation of normal SCs. Cadmium
      has been linked to human pancreatic cancer. OBJECTIVE: We studied cadmium
      exposure of human pancreatic ductal epithelial (HPDE) cells and whether SCs may
      be targeted in this process. METHODS: We chronically exposed HPDE cells to low
      level cadmium (1 MUM) for <= 29 weeks. Nonadherent spheroid formation was used to
      indicate CSC-like cell production, and we assessed tumor cell characteristics in
      such spheres. Assessed tumor cell characteristics including secretion of matrix
      metalloproteinase-9 (MMP-9), invasion, and colony formation were fortified by
      evaluating expression of relevant genes by real-time reverse transcription
      polymerase chain reaction and by Western blot. RESULTS: Increased MMP-9 secretion
      and overexpression of the pancreatic cancer marker S100P occurred in chronic (29
      weeks of exposure) cadmium-exposed (CCE) cells. CCE cells also showed markedly
      higher colony formation and invasion, typical of cancer cells. Floating "spheres"
      of viable cells, known to contain an abundance of normal SCs or CSCs, form in
      vitro with many cell types. CCE cells produced 3-fold more spheres than control
      cells and were more invasive, secreted more MMP-9, and overexpressed markers for
      pancreatic SCs/CSCs (i.e., CXCR4, OCT4, CD44) and S100P, a marker for pancreatic
      cancer. CCE-derived spheres rapidly produced aggressive, highly branched, and
      poorly differentiated glandular-like structures in Matrigel. CONCLUSIONS: Chronic
      cadmium exposure produced multiple tumor cell characteristics in HPDE cells and
      CCE cell-derived spheres. These data support the plausibility of cadmium as a
      human pancreatic carcinogen.

PMID- 22626612
TI  - Multiple intussusceptions revealing metastases from renal carcinoma to the small
      intestine.
AB  - Malignant tumors of the kidney represent rare primary intestinal metastases. They
      occur in 4% of cases. These intestinal metastases are mainly the small intestine;
      colon is a rare achievement. We report a case of small intestine metastatic of a
      tubulo-pappilary carcinoma revealed by a multiple intussusception a year after
      nephrectomy. The cross-sectional imaging (ultrasound and CT) was the gold
      standard for positive diagnosis of intussusception and the nature of secondary
      underlying tumor. Intestinal metastases of renal cell carcinoma sometimes occur
      many years after nephrectomy. On imaging, metastases simulate all tumor aspects.

PMID- 22626613
TI  - DNA extraction method from bones using Maxwell(r) 16.
AB  - This paper describes the automated purification of DNA extracted from human bones
      using Maxwell(r) 16 bench top instrument. Analysis of nuclear short tandem
      repeats (STR) is invaluable in identification of human remains exhumed from mass
      graves in Croatia. Up to today 4683 skeletal remains have been recovered and for
      897 human remains identity has not been determined. DNA has been extracted from
      70% of all unidentified samples. For more than 90% of the samples nuclear STR
      profiles have been obtained using either organic phenol/chloroform method or
      silica-column purification for the extraction of DNA from bones or teeth. In
      order to evaluate a Maxwell(r) 16 DNA extraction performance 40 bone samples with
      different stage of decomposition were analyzed. The efficacy of manual silica
      based extraction and an automated purification was compared. The DNA yield per
      gram of starting material, removal of inhibitors and the quality of resulting STR
      profiles of the Maxwell extracts from duplicate amplifications were evaluated.
      The results show that Maxwell 16 platform can be used instead of manual DNA
      extraction procedures.

PMID- 22626614
TI  - Hand-head coordination changes from discrete to reciprocal hand movements for
      various difficulty settings.
AB  - The parameters dictating the temporal hand-head coordination during visually
      corrected movements remain elusive. Here we examine the effects of the nature
      (discrete vs reciprocal) and the difficulty (ID of 4.7, 5.7 and 6.7 bits) of the
      task on the temporal hand-head coordination during a Fitts' like paradigm.
      Subjects aimed at a single target (discrete movement) or alternately to two
      targets (reciprocal movements). Head movements were unaffected by the ID during
      discrete movements. This was not the case during reciprocal movements where they
      were (1) smaller in duration and amplitude than during discrete movements and (2)
      increased in duration and amplitude with an increasing ID. To measure the
      temporal hand-head coordination, hand-head latencies were calculated at the
      onset, peak speed and offset of each movement. Offset latencies remained positive
      (i.e. the hand reached the target after the head stopped) for all IDs during
      reciprocal but not during discrete movements. Altogether, different patterns of
      temporal hand-head coordination were observed between discrete and reciprocal
      movements as well as between IDs, suggesting the hand-head coordination does not
      follow a fixed rule but is adjusted to task requirements.

PMID- 22626615
TI  - Tramadol induces conditioned place preference in rats: interactions with morphine
      and buprenorphine.
AB  - Surveys and drug surveillance have demonstrated that the abuse liability of
      tramadol is considerably low in the general population but appears to be higher
      in opiate addicts, and this difference could attribute to the poly-drug abuse of
      opioid addicts, although this hypothesis has not been tested in the laboratory.
      The present study examined the interactions between tramadol and a full MU opioid
      receptor agonist morphine or a partial MU opioid receptor agonist buprenorphine
      in a conditioned place preference (CPP) paradigm in rats. Rats were conditioned
      with tramadol (2-54 mg/kg, i.p.), morphine (0.125-8 mg/kg, s.c.), buprenorphine
      (0.01-0.316 mg/kg, s.c.) or a combination of a subeffective dose of tramadol
      (2mg/kg) with a subeffective dose of morphine or buprenorphine and the CPP effect
      was measured. The retention of CPP effect was also examined. Tramadol, morphine
      and buprenorphine all produced a dose-dependent and significant CPP. A smaller
      dose of tramadol (2mg/kg) enhanced morphine- and buprenorphine-induced CPP and
      shifted the dose-effect curves of both drugs leftward. In addition, the
      combination of tramadol with morphine or buprenorphine prolonged the retention of
      CPP. These findings indicate that tramadol potentiates the rewarding effects of
      morphine or buprenorphine largely in an additive manner and support the general
      contention that tramadol has relatively low abuse liability.

PMID- 22626616
TI  - [Healthy and participative schools: evaluation of a public health strategy].
AB  - OBJECTIVE: Let's foster health! is an intervention strategy in health promotion
      for use in primary and secondary schools and based on evidence, participation,
      consensus and the commitment of all members of the educational community. The aim
      of the present study was to evaluate this strategy according to the achievement
      of two specific aims: 1) the educational community's opinion of the
      implementation process, and 2) changes due to the strategy. METHODS: From 2010 to
      2011, researchers conducted 1) a descriptive qualitative study to evaluate the
      implementation process by identifying facilitators, barriers, needs and
      suggestions using focus groups and in-depth interviews, and 2) a before-and-after
      quasi-experimental study with a comparison group using specific questionnaires
      aimed at evaluating participation and compliance with features of Health
      Promoting Schools. Both education and health professionals were used as
      information sources. RESULTS: The main facilitators were the involvement of
      management structures and faculty during implementation. The most important
      barrier was lack of time and resources. Participating centers in Let's foster
      health! complied with the parameters defining Health Promoting Schools to a
      higher degree than the control group: these centers became more involved,
      carrying out more preventive actions and implementing health-related decisions in
      the curriculum and the center's policy. CONCLUSIONS: Let's foster health! is a
      participative and community intervention strategy based on the characteristics of
      Health Promoting Schools that encourages health-promoting environments.

PMID- 22626617
TI  - Nonmydriatic ultrawide field retinal imaging compared with dilated standard 7
      field 35-mm photography and retinal specialist examination for evaluation of
      diabetic retinopathy.
AB  - PURPOSE: To compare nonmydriatic stereoscopic Optomap ultrawide field images with
      dilated stereoscopic Early Treatment Diabetic Retinopathy Study 7-standard field
      35-mm color 30-degree fundus photographs (ETDRS photography) and clinical
      examination for determining diabetic retinopathy (DR) and diabetic macular edema
      (DME) severity. DESIGN: Single-site, prospective, comparative, instrument
      validation study. METHODS: One hundred three diabetic patients (206 eyes)
      representing the full spectrum of DR severity underwent nonmydriatic ultrawide
      field 100-degree and 200-degree imaging, dilated ETDRS photography, and dilated
      fundus examination by a retina specialist. Two independent readers graded images
      to determine DR and DME severity. A third masked retina specialist adjudicated
      discrepancies. RESULTS: Based on ETDRS photography (n = 200), the results were as
      follows: no DR (n = 25 eyes [12.5%]), mild nonproliferative DR (NPDR; 47
      [23.5%]), moderate NPDR (61 [30.5%]), severe NPDR (11 [5.5%]), very severe NPDR
      (3 [1.5%]), and proliferative DR (52 [2.5%]). One (0.5%) eye was ungradable and 6
      eyes did not complete ETDRS photography. No DME was found in 114 eyes (57.0%),
      DME was found in 28 eyes (14.0%), and clinically significant DME was found in 47
      eyes (23.5%), and 11 (5.5%) eyes were ungradable. Exact DR severity agreement
      between ultrawide field 100-degree imaging and ETDRS photography occurred in 84%,
      with agreement within 1 level in 91% (K(W) = 0.85; K = 0.79). Nonmydriatic
      ultrawide field images exactly matched clinical examination results for DR in 70%
      and were within 1 level in 93% (K(W) = 0.71; K = 0.61). Nonmydriatic ultrawide
      field imaging acquisition time was less than half that of dilated ETDRS
      photography (P < .0001). CONCLUSIONS: Nonmydriatic ultrawide field images compare
      favorably with dilated ETDRS photography and dilated fundus examination in
      determining DR and DME severity; however, they are acquired more rapidly. If
      confirmed in broader diabetic populations, nonmydriatic ultrawide field imaging
      may prove to be beneficial in DR evaluation in research and clinical settings.

PMID- 22626618
TI  - Microbiologic and histopathologic assessment of corneal biopsies in the
      evaluation of microbial keratitis.
AB  - PURPOSE: To investigate the utility of corneal biopsy in the evaluation of
      infectious keratitis; to compare results of culture and histopathologic
      examination of the same specimens; to investigate potential factors related to
      positive biopsy results. DESIGN: Retrospective, observational case series.
      METHODS: We reviewed medical records for all patients who underwent corneal
      biopsy because of infectious keratitis at the Jules Stein Eye Institute from June
      1989 through June 2009. In general, biopsy specimens were both cultured and
      examined histopathologically. Lesion size, lesion progression, and interval from
      presentation to biopsy were analyzed as possible predictors of positive biopsies.
      RESULTS: Organisms were identified in 20 of 48 (42%) consecutive biopsies
      (positive cultures in 9 of 47 cases [19%]; positive histopathologic examination
      in 19 of 47 cases [40%]). Culture and histopathologic results were concordant in
      30 of 46 biopsies (65%) for which both techniques were performed; 10 of the 16
      discordant cases were culture-negative/histopathology-positive, while the
      remaining 6 had positive but discordant results for the 2 techniques (cultures
      all showed bacteria; histopathologic examination showed fungi or cysts consistent
      with Acanthamoeba sp.). Corneal biopsy revealed microorganisms in 12 of 27
      patients (44%) with negative cultures of corneal scrapings obtained at
      presentation. None of the potential risk factors was statistically associated
      with positive biopsies. CONCLUSIONS: Corneal biopsy can be useful for identifying
      the cause of infectious keratitis in selected cases. Culture and histopathologic
      examination can provide complementary information, but discordant results may
      occur. Acanthamoebic and fungal infections are more likely to be identified by
      histopathologic examination.

PMID- 22626619
TI  - Short-term changes of Basal laminar drusen on spectral-domain optical coherence
      tomography.
AB  - PURPOSE: To determine if small hard drusen in patients with basal laminar drusen
      show short-term changes. DESIGN: Prospective observational case series. METHODS:
      Ten subjects with basal laminar drusen were longitudinally followed during a
      period of 4 months by spectral-domain optical coherence tomography. Drusen that
      showed a spontaneous change in volume were further analyzed according to 5
      morphologic parameters: shape, reflectivity, homogeneity, and concurring
      photoreceptor layer/retinal pigment epithelium damage. Odds ratios (OR) and risk
      for regression and progression of drusen volumes were calculated. RESULTS: One
      hundred and five small hard drusen in 19 eyes showed a spontaneous change in
      volume over the period of follow-up. Drusen with a "pointed" shape were
      significantly associated (P = .031; OR 4.89; 95% confidence interval [CI] 1.16
      20.67) with spontaneous progression in drusen volume, with a chance of 0.80 (95%
      CI 0.55-0.93) to progress. Drusen that showed a decreased reflectivity of
      overlying photoreceptor layer (P = .041; OR 7.67; 95% CI 1.09-54.24) or retinal
      pigment epithelium (P = .022; OR 12.38; 95% CI 1.44-106.57), showed a significant
      association with spontaneous regression in drusen volume, with chances of
      regression of 0.86 (95% CI 0.41-0.98) and 0.89 (95% CI 0.49-0.99), respectively.
      CONCLUSION: Small hard drusen in patients with the basal laminar drusen phenotype
      are subject to a process of short-term remodeling. The dynamic nature of this
      disease points to high biochemical activity that may be sensitive to future
      pharmacologic treatment strategies. In addition, these short-term changes of
      drusen may be a source of misclassification in disease staging.

PMID- 22626620
TI  - RAND-like appropriateness methodology consensus for primary open-angle glaucoma
      in Latin America.
AB  - PURPOSE: To report the results of a Latin American consensus panel regarding the
      diagnosis and management of primary open-angle glaucoma and to compare these
      results with those from a similar panel in the United States. DESIGN: A RAND-like
      (Research and Development) appropriateness methodology was used to assess
      glaucoma practice in Latin America. METHODS: The 148 polling statements created
      for the RAND- like analysis in the United States and 10 additional statements
      specific to glaucoma care in Latin America were presented to a panel of Latin
      American glaucoma experts. Panelists were polled in private using the RAND- like
      methodology before and after the panel meeting. RESULTS: Consensus agreement or
      disagreement among Latin American experts was reached for 51.3% of statements
      before the meeting and increased to 66.5% in the private, anonymous meeting after
      polling (79.0% agreement, 21.0% disagreement). Although there was a high degree
      of concordance (111 of 148 statements; 75%) between the results of this Latin
      American panel and the United States panel, there were some notable exceptions
      relating to diagnostic and therapeutic decision making. CONCLUSIONS: This RAND
      like consensus methodology provides a perspective of how Latin American glaucoma
      practitioners view many aspects of glaucoma and compares these results with those
      obtained using a similar methodology from practitioners in the United States.
      These findings may be helpful to ophthalmologists providing glaucoma care in
      Latin America and in other regions of the world.

PMID- 22626621
TI  - New molecular markers for fungal phylogenetics: two genes for species-level
      systematics in the Sordariomycetes (Ascomycota).
AB  - Although significant progress has been made resolving deep branches of the fungal
      tree of life, many fungal systematists are interested in species-level questions
      to both define species and assess fungal biodiversity. Fungal genome sequences
      are a useful resource to systematic biologists for developing new phylogenetic
      markers that better represent the whole genome. Here we report primers for two
      newly identified single-copy protein-coding genes, FG1093 and MS204, for use with
      ascomycetes. Although fungi were the focus of this study, this methodological
      approach could be easily applied to marker development for studies of other
      organisms. The tests used here to assess phylogenetic informativeness are
      computationally rapid, require only rudimentary datasets to evaluate existing or
      newly developed markers, and can be applied to other non-model organisms to
      assist in experimental design of phylogenetic studies. Phylogenetic utility of
      the markers was tested in two genera, Gnomoniopsis and Ophiognomonia
      (Gnomoniaceae, Diaporthales). The phylogenetic performance of beta-tubulin, ITS,
      and tef-1alpha was compared with FG1093 and MS204. Phylogenies inferred from
      FG1093 and MS204 were largely in agreement with beta-tubulin, ITS, and tef-1alpha
      although some topological conflict was observed. Resolution and support for
      branches differed based on the combination of markers used for each genus. Based
      on two independent tests of phylogenetic performance, FG1093 and MS204 were
      determined to be equal to or better than beta-tubulin, ITS, and tef-1alpha in
      resolving species relationships. Differences were found in site-specific rate of
      evolution in all five markers. In addition, isolates from 15 orders and 22
      families of Ascomycota were screened using primers for FG1093 and MS204 to
      demonstrate primer utility across a wide diversity of ascomycetes. The primer
      sets for the newly identified genes FG1093 and MS204 and methods used to develop
      them are useful additions to the ascomycete systematists' toolbox.

PMID- 22626622
TI  - Catchment-to-reef continuum: Case studies from the Great Barrier Reef. A special
      issue--Marine Pollution Bulletin 2012.

PMID- 22626623
TI  - Contaminant concentrations, biochemical and hematological biomarkers in blood of
      West Indian manatees Trichechus manatus from Brazil.
AB  - The West Indian manatee Trichechus manatus is threatened with extinction in
      Brazil, and this study focused on nondestructive blood samples analyzed for
      metals, polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), as
      well as biochemical and hematological biomarkers. Studied manatees were kept at
      Projeto Peixe-Boi headquarters in Pernambuco State, and at two natural areas in
      estuaries where they are released to the wild. Manatees kept at the natural
      estuary in Paraiba State have blood concentrations of Al, Pb, Cd, Sn that are 11,
      7, 8 and 23 times greater, respectively, than the concentrations found in blood
      of animals from the same species in Florida, USA. An inhibition of
      butyrylcholinesterase in manatees kept at the two reintroduction sites in Alagoas
      and Paraiba States indicated possible exposure of the animals to cholinesterase
      inhibitor insecticides. PCBs and OCPs were not detected. Results from this study
      will help delineate conservation efforts in the region.

PMID- 22626624
TI  - Viral interactions with the host and microbiota in the intestine.
AB  - This review explores the recent advances that have been made in our understanding
      of host viral interactions in the intestine. Technical advances have allowed the
      initial definition of intestinal viromes in a number of species including humans.
      Important advances in our knowledge of the host response to viral infection have
      shown that interferon lambda has a role that is unique from type I interferons in
      the intestine. Lastly, our understanding of virally induced phenotypes has
      expanded through new studies that show bacteria can play an important role in the
      outcome of viral infection in the intestine.

PMID- 22626625
TI  - Telomeres and immune competency.
AB  - Telomeres are essential for the integrity of chromosomes and for cellular
      replication. Attrition of telomeres occurs during DNA replication owing to the
      inability of conventional DNA polymerase to replicate chromosomal termini and the
      insufficient compensation for telomere loss by telomerase, an enzyme that
      synthesizes telomeric DNA. A number of genetic defects have been described in
      humans and in animal models that cause accelerated telomere attrition, in turn
      leading to severe phenotypes of hematopoietic and other proliferating cells.
      Telomere length, most frequently measured as an average value in heterogeneous
      peripheral blood leukocyte populations in humans, has been associated with a wide
      range of health conditions and diseases of immune and non-immune cells. Here, I
      review recent studies of telomere length dynamics with particular relevance to
      immune function.

PMID- 22626626
TI  - Inventory of non starter lactic acid bacteria from ripened Parmigiano Reggiano
      cheese as assessed by a culture dependent multiphasic approach.
AB  - The objective of this study was to investigate microbial species diversity and
      strain complexity of the cultivable non starter lactic acid bacteria (NSLAB)
      occurring in 31 ripened Parmigiano Reggiano (PR) cheeses. Dereplication of 127
      lactobacilli isolates by (GTG)(5)-PCR fingerprinting yielded a total of 51
      genotypes. Phylogenetic relatedness of all the genotypes with known Lactobacillus
      species was determined by a novel combined amplified 16S rDNA restriction
      analysis (16S-ARDRA), species-specific PCR assays and 16S rRNA gene sequencing.
      The species Lactobacillus rhamnosus and Lactobacillus paracasei comprise the
      largest portions of the cultivable NSLAB community in PR cheese, with an inter
      individual diversity ranging from one to four dominant genotypes per sample.
      Lactobacillus casei, Lactobacillus harbinensis and Lactobacillus fermentum
      species were also detected at low frequency. The data showed differences in
      cultivable NSLAB population, with an overall decrease in diversity and complexity
      from early to advanced stages of ripening. Finally the de-replicated collection
      of genotypes resulting from this work is the bases for further functional
      screening.

PMID- 22626627
TI  - Tamarind (Tamarindus indica) fruit shell carbon: A calcium-rich promising
      adsorbent for fluoride removal from groundwater.
AB  - Tamarindus indica fruit shells (TIFSs) are naturally calcium rich compounds. They
      were impregnated with ammonium carbonate and then carbonized, leading to ammonium
      carbonate activated ACA-TIFS carbon. The resulting materials and carbon arising
      from virgin fruit shells V-TIFS were characterized and assayed as adsorbent for
      the removal of fluoride anions from groundwater. The fluoride scavenging ability
      of TIFS carbons was due to naturally dispersed calcium compounds. X-ray
      diffraction (XRD) showed that TIFS carbon contained a mixture of calcium oxalate
      and calcium carbonate. Batch studies on the fluoride removal efficiency of TIFS
      carbons with respect to contact time, pH, initial fluoride concentration, and co
      ion interference were conducted. Applicability of various kinetic models (viz.,
      pseudo-first-order, pseudo-second-order, intra-particle diffusion and Elovich)
      and sorption isotherms were tested for batch techniques. The fluoride removal
      capacity of TIFS carbons was found to be 91% and 83% at a pH of 7.05 for V-TIFS
      and ACA-TIFS carbons, respectively. The practical applicability of TIFS carbons
      using groundwater samples was approved. The fluoride removal was greater in
      groundwater without hydrogen carbonate ions than those containing these ions. The
      characterizations of fluoride unloaded and loaded TIFS carbons were done by SEM
      and XRD studies.

PMID- 22626628
TI  - Development of immobilized biophotonic beads consisting of Photobacterium
      leiognathi for the detection of heavy metals and pesticide.
AB  - The present communication deals with construction of immobilized robust
      biophotonic bead using P. leiognathi, a marine luminescent bacterium for their
      possible application in monitoring of environmental toxicants. Immobilization
      efficiency of agar, carrageenan and sodium alginate was evaluated separately in
      terms of luminescence response and was recorded as 30.3, 77.4 or 99.5%,
      respectively. Under optimized storage conditions, the luminescent response of P.
      leiognathi in the immobilized state was studied over a period of 30 days. These
      biophotonic beads were further used as a rapid and reliable optical biosensing
      tool for the detection of heavy metals [Hg(II), As(V) or Cd(II)] and pesticide
      [2,4-dichlorophenoxyacetic acid (2,4-D)] in water systems. The concentration
      range for the detection of Hg(II), As(V), Cd(II) and 2,4-D was 2-32ppm, 4-128ppm,
      16-512ppm and 100-600ppm, respectively, while corresponding sensitivity threshold
      was 2.0ppm, 4.0ppm, 16.0ppm and 100ppm. A comparison of inhibition constant
      (K(d)) (or EC(20)) values indicated that the sensitivity thresholds rank as
      Hg(II)>As(V)>Cd(II)>2,4-D. Moreover, the time taken for the detection of heavy
      metals and pesticide was less than 30min. Using the bioluminescence inhibition
      method, the concentration of heavy metals and pesticide could be predicted.

PMID- 22626629
TI  - Removal of cesium from simulated liquid waste with countercurrent two-stage
      adsorption followed by microfiltration.
AB  - Copper ferrocyanide (CuFC) was used as an adsorbent to remove cesium. Jar test
      results showed that the adsorption capacity of CuFC was better than that of
      potassium zinc hexacyanoferrate. Lab-scale tests were performed by an adsorption
      microfiltration process, and the mean decontamination factor (DF) was 463 when
      the initial cesium concentration was 101.3MUg/L, the dosage of CuFC was 40mg/L
      and the adsorption time was 20min. The cesium concentration in the effluent
      continuously decreased with the operation time, which indicated that the used
      adsorbent retained its adsorption capacity. To use this capacity, experiments on
      a countercurrent two-stage adsorption (CTA)-microfiltration (MF) process were
      carried out with CuFC adsorption combined with membrane separation. A calculation
      method for determining the cesium concentration in the effluent was given, and
      batch tests in a pressure cup were performed to verify the calculated method. The
      results showed that the experimental values fitted well with the calculated
      values in the CTA-MF process. The mean DF was 1123 when the dilution factor was
      0.4, the initial cesium concentration was 98.75MUg/L and the dosage of CuFC and
      adsorption time were the same as those used in the lab-scale test. The DF
      obtained by CTA-MF process was more than three times higher than the single-stage
      adsorption in the jar test.

PMID- 22626631
TI  - MRI mean diffusivity detects widespread brain degeneration in multiple sclerosis.
AB  - We investigated the magnetic resonance imaging (MRI) findings of 32 multiple
      sclerosis (MS) patients using voxel-based morphometry (VBM) and voxel-based
      analysis of white matter fluid-attenuated inversion recovery image (FLAIR) high
      intensity lesions and diffusion tensor imaging (DTI). Compared with 18 healthy
      controls, MS patients showed gray matter volume reduction in the thalamus,
      hypothalamus, caudate, limbic lobe, and frontal lobe. A marked volume reduction
      of white matter was evident along the ventriculus lateralis and corpus callosum.
      FLAIR high-intensity lesions were observed beside the ventriculus lateralis. DTI
      revealed reduced fractional anisotropy areas similar to those of the FLAIR high
      intensity lesions. Changes in the volume of increased mean diffusivity (MD) were
      the most widespread and extended to normal-appearing white matter (p<0.001).
      Multiple regression analysis revealed that MD values were significantly
      correlated with both disease duration (r=0.381, p=0.032) and expanded disability
      status scale scores (EDSS) (r=0.393, p=0.026). This study demonstrated that
      combined voxel-based analysis for volumetry, FLAIR high-intensity lesions, and
      DTI could reveal widespread brain abnormalities in MS patients. Furthermore, DTI,
      especially MD, showed far more widespread brain degeneration than other MRI
      parameters, and was significantly correlated with both severity and disease
      duration.

PMID- 22626630
TI  - 3D evaluation of postoperative swelling in treatment of bilateral mandibular
      fractures using 2 different cooling therapy methods: a randomized observer blind
      prospective study.
AB  - Surgical treatment and complications in patients with mandibular fractures leads
      to a significant degree of tissue trauma resulting in common postoperative
      symptoms and signs of pain, facial swelling, mandible dysfunction and limited
      mouth opening (trismus). Beneficial effects of local cold treatment on
      postoperative swelling, oedema, pain, inflammation and haemorrhage, as well as
      the reduction of metabolism, bleeding and haematomas have been described. The aim
      of this study was to compare postoperative cooling therapy by cooling compresses
      with the water-circulating cooling face mask by Hilotherm((r)) in terms of
      beneficial effects on postoperative facial swelling, pain, mandible dysfunction,
      trismus and neurological complaints. Thirty-two patients were assigned for
      treatment of bilateral mandibular fractures and were divided randomly into
      treatment either with the Hilotherm((r)) cooling face mask or with conventional
      cooling with cooling compresses. Cooling was initiated as soon as possible after
      surgery until postoperative day 3 continuously for 12h daily. Facial swelling was
      quantified by a 3D optical scanning technique. Pain, neurological complaints,
      mandibular dysfunction and the degree of mouth opening were measured for each
      patient. Patients receiving cooling therapy by Hilotherm((r)) demonstrated less
      facial swelling, less pain, a tendency to fewer neurological complaints and were
      more satisfied when compared to conventional cooling. Hilotherm((r)) is more
      superior in the management of postoperative swelling and pain after treatment of
      bilateral mandibular fractures when compared to conventional cooling.

PMID- 22626632
TI  - Positive attitude towards life and emotional expression as personality phenotypes
      for centenarians.
AB  - Centenarians have been reported to share particular personality traits including
      low neuroticism and high extraversion and conscientiousness. Since these traits
      have moderate to high heritability and are associated with various health
      outcomes, personality appears linked to bio-genetic mechanisms which may
      contribute to exceptional longevity. Therefore, the present study sought to
      detect genetically-based personality phenotypes in a genetically homogeneous
      sample of centenarians through developing and examining psychometric properties
      of a brief measure of the personality of centenarians, the Personality Outlook
      Profile Scale (POPS). The results generated two personality
      characteristics/domains, Positive Attitude Towards Life (PATL: optimism,
      easygoing, laughter, and introversion/outgoing) and Emotional Expression (EE:
      expressing emotions openly and not bottling up emotions). These domains
      demonstrated acceptable concurrent validity with two established personality
      measures, the NEO-Five Factor Inventory and Life Orientation Test-Revised.
      Additionally, centenarians in both groups had lower neuroticism and higher
      conscientiousness than the US adult population. Findings suggest that the POPS is
      a psychometrically sound measure of personality in centenarians and capture
      personality aspects of extraversion, neuroticism, and conscientiousness, as well
      as dispositional optimism which may contribute to successful aging.

PMID- 22626633
TI  - Comparison of neuroleptic malignant syndrome induced by first- and second
      generation antipsychotics.
AB  - BACKGROUND: Reports of neuroleptic malignant syndrome (NMS) induced by second
      generation antipsychotic drugs highlight a propensity for atypical clinical
      presentations. AIMS: To systematically compare the clinical profile of NMS
      induced by first- (1G-NMS) and second-generation antipsychotic drugs (2G-NMS).
      METHOD: The Australian Adverse Drug Reaction Advisory Committee (ADRAC) database
      was searched to identify individuals with NMS reported between April 1994 and
      September 2010. The clinical characteristics of 208 people with NMS induced by
      monotherapy with first- or second-generation antipsychotic drugs, as well as
      presenting features of NMS, were compared. RESULTS: The individuals with 2G-NMS
      were younger and more likely to have a psychotic disorder diagnosis. The features
      of NMS in the two groups were very similar, except that people with 2G-NMS were
      less likely to present with rigidity or extrapyramidal signs compared with those
      with 1G-NMS. This difference was due to the lower rates of rigidity in those with
      clozapine-induced NMS. Mortality was considerably lower for those with 2G-NMS
      (3.0%) compared with 1G-NMS (16.3%), and the former were more likely to have
      received supportive treatment. CONCLUSIONS: The clinical profile of 2G-NMS is
      largely similar to 1G-NMS, with clozapine-induced NMS being differentiated by the
      relative lack of rigidity as a feature. Mortality is lower for 2G-NMS.

PMID- 22626634
TI  - Relationship between progression of brain white matter changes and late-life
      depression: 3-year results from the LADIS study.
AB  - BACKGROUND: Brain white matter changes (WMC) and depressive symptoms are linked,
      but the directionality of this association remains unclear. AIMS: To investigate
      the relationship between baseline and incident depression and progression of
      white matter changes. METHOD: In a longitudinal multicentre pan-European study
      (Leukoaraiosis and Disability in the elderly, LADIS), participants aged over 64
      underwent baseline magnetic resonance imaging (MRI) and clinical assessments.
      Repeat scans were obtained at 3 years. Depressive outcomes were assessed in terms
      of depressive episodes and the Geriatric Depression Scale (GDS). Progression of
      WMC was measured using the modified Rotterdam Progression scale. RESULTS:
      Progression of WMC was significantly associated with incident depression during
      year 3 of the study (P = 0.002) and remained significant after controlling for
      transition to disability, baseline WMC and baseline history of depression. There
      was no significant association between progression of WMC and GDS score, and no
      significant relationship between progression of WMC and history of depression at
      baseline. CONCLUSIONS: Our results support the vascular depression hypothesis and
      implicate WMC as causal in the pathogenesis of late-life depression.

PMID- 22626636
TI  - SKI-1/S1P inhibition: a promising surrogate to statins to block hepatitis C virus
      replication.
AB  - Hepatitis C virus (HCV) is often associated with steatosis, cirrhosis and
      hepatocellular carcinoma (HCC). Statins (HMG-CoAR inhibitors) have been shown to
      exert an antiviral effect in vitro, principally on replicon harboring cells, but
      the effect of their use alone in vivo remains controversial. In clinical trials,
      when used in combination with the standards of care (SOC), they led to an
      increased proportion of sustained virological responder (SVR). Here we
      investigated the implication of SKI-1/S1P, a master lipogenic pathways regulator
      upstream of HMG-CoAR, on different steps of HCV life cycle. We compared the HCV
      antiviral effect of the most potent SKI-1/S1P small molecule inhibitor (PF
      429242) with a set of two statins on different steps of the viral life cycle, and
      showed that SKI-1/S1P inhibitor blocked HCVcc (strain JFH-1) RNA replication
      (EC(50)= 5.8 MUM) more efficiently than statins. Moreover, we showed that PF
      429242 could reduce lipid droplets accumulation in Huh7 cells. Interestingly, PF
      429242 dramatically reduced infectious particles production (EC(90)= 4.8 MUM).
      Such inhibition could not be achieved with statins. SKI-1/S1P activity is thus
      essential for viral production and its inhibition should be considered for
      antiviral drug development.

PMID- 22626635
TI  - Childhood attention problems and socioeconomic status in adulthood: 18-year
      follow-up.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) has been associated
      with socioeconomic difficulties later in life. Little research in this area has
      been based on longitudinal and community studies. AIMS: To examine the
      relationship between childhood attention problems and socioeconomic status 18
      years later. METHOD: Using a French community sample of 1103 youths followed from
      1991 to 2009, we tested associations between childhood attention problems and
      socioeconomic status between ages 22 and 35 years, adjusting for potential
      childhood and family confounders. RESULTS: Individuals with high levels of
      childhood attention problems were three times more likely to experience
      subsequent socioeconomic disadvantage than those with low levels of attention
      problems (odds ratio 3.44, 95% CI 1.72-6.92). This association remained
      statistically significant even after adjusting for childhood externalising
      problems, low family income, parental divorce and parental alcohol problems.
      CONCLUSIONS: This longitudinal community-based study shows an association between
      childhood attention problems and socioeconomic disadvantage in adulthood. Taking
      into account ADHD and associated difficulties could help reduce the long-term
      socioeconomic burden of the disorder.

PMID- 22626637
TI  - The European Virus Archive: a new resource for virology research.
AB  - The European Virus Archive (EVA) was conceived as a direct response to the need
      for a coordinated and readily accessible collection of viruses that could be made
      available to academia, public health organisations and industry, initially within
      Europe, but ultimately throughout the world. Although scientists worldwide have
      accumulated virus collections since the early twentieth century, the quality of
      the collections and the viruses collected may vary according to the personal
      interests and agenda of the scientists. Moreover, when laboratories are re
      organised or closed, collections are no longer maintained and gradually cease to
      exist. The tragedy of 9/11 and other disruptive activities have also meant that
      some previously available biological reagents are no longer openly exchanged
      between countries. In 2008, funding under the FP7-EU infrastructure programme
      enabled the initiation of the EVA. Within three years, it has developed from a
      consortium of nine European laboratories to encompass associated partners in
      Africa, Russia, China, Turkey, Germany and Italy. There is every reason to
      believe that EVA will continue to expand and ultimately exist as a globally
      networked, quality-controlled non-profit archive for the benefit of science.
      Organizations or individuals who would like to be considered as contributors are
      invited to contact the EVA coordinator, Jean-Louis Romette, at jean
      louis.romette@univmed.fr.

PMID- 22626638
TI  - Optimization and qualification of a multiplex bead array to assess cytokine and
      chemokine production by vaccine-specific cells.
AB  - The magnitude and functional phenotype (e.g. proliferation, immune stimulation)
      of vaccine-induced T-cell responses are likely to be critical in defining
      responses that can control pathogenic challenge. Current multi-parameter flow
      cytometric techniques may not be sufficient to measure all of these different
      functions, since characterizing T-cell responses by flow cytometry is presently
      limited to concurrent measurement of at most 10 cytokines/chemokines. Here, we
      describe extensive studies conducted using standardized GCLP procedures to
      optimize and qualitatively/quantitatively qualify a multiplex bead array (MBA)
      performed on supernatant collected from stimulated peripheral blood mononuclear
      cells (PBMC) to assess 12 cytokines and chemokines of interest. Our optimized MBA
      shows good precision (intra-assay, inter-day, inter-technician; coefficients of
      variation <30%) and linearity for most of the analytes studied. We also developed
      positivity criteria that allow us to define a response as positive or negative
      with a high degree of confidence. In conclusion, we provide a detailed
      description of the qualification of an MBA, which permits quantitative and
      qualitative evaluation of vaccine-induced immunogenicity and analysis of immune
      correlates of protection. This assay provides an excellent complement to the
      existing repertoire of assays for assessing immunogenicity in HIV vaccine
      clinical trials.

PMID- 22626639
TI  - Improved detection of synovial boundaries in ultrasound examination by using a
      cascade of active-contours.
AB  - Rheumatoid arthritis (RA) is a chronic multisystemic autoimmune disease, with an
      unclear etiopathogenesis. Its early diagnosis and activity assessment are
      essential to adjust the proper therapy. Among the different imaging techniques,
      ultrasonography (US) allows direct visualization of early inflammatory joint
      changes as synovitis, being also rapidly performed and easily accepted by
      patients. We propose an algorithm to semi-automatically detect synovial
      boundaries on US images, requiring minimal user interaction. In order to identify
      the synovia-bone and the synovia-soft tissues interfaces, and to tackle the
      morphological variability of diseased joints, a cascade of two different active
      contours is developed, whose composition corresponds to the whole synovial
      boundary. The algorithm was tested on US images acquired from proximal
      interphalangeal (PIP) and metacarpophalangeal (MCP) finger joints of 34 subjects.
      The results have been compared with a consensus manual segmentation. We obtained
      an overall mean sensitivity of 85+/-13%, and a mean Dice's similarity index of
      80+/-8%, with a mean Hausdorff distance from the manual segmentation of 28+/-10
      pixels (approximately 1.4+/-0.5mm), that are a better performance than those
      obtained by the raters with respect to the consensus.

PMID- 22626640
TI  - Fine-needle aspiration cytology in the management of parotid masses: evaluation
      of 249 patients.
AB  - INTRODUCTION: The role of fine-needle aspiration cytology (FNAC) in the
      management of parotid tumours is still the subject of controversy. The purpose of
      this study was to determine the diagnostic value of FNAC in our institution in
      order to define its place in the diagnostic strategy. PATIENTS AND METHODS: This
      retrospective study was based on 249 patients who had undergone preoperative FNAC
      before being operated in our institution between 2001 and 2008. All examinations
      were performed and interpreted by the same experienced pathologist. RESULTS:
      Among the 249 patients included in this study, 187 (75%) had a benign tumour and
      62 (25%) had a malignant tumour. No complications of FNAC were observed.
      Cytological findings were non-contributory in 47 patients (18%). The sensitivity
      of FNAC for the diagnosis of malignancy was 80% with a specificity of 89.5%.
      Among the 11 false-negative results, lymphomas and low-grade mucoepidermoid
      carcinomas were the most common histological types. Among the 16 false-positive
      results, Warthin's tumours, pleomorphic adenomas and lymphoepithelial lesions
      were the most common histological types. Accurate histological classification of
      the tumour was reported in 79.5% of cases (86% for benign tumours and 44% for
      malignant tumours). CONCLUSION: FNAC is a reliable examination providing
      important information to the surgeon in the preoperative diagnostic assessment.

PMID- 22626641
TI  - Dopaminergic activity coincides with stimulus detection by the frontal lobe.
AB  - For midbrain dopamine (DA) neurons to respond to sensory events, the presence of
      a stimulus must first be detected. Where is the signal that activates DA neurons
      coming from? Here we show that DA responses to a vibrotactile stimulus lag
      significantly behind those of the primary somatosensory cortex, but they arise
      with a latency that closely matches the onset of premotor neurons known to encode
      perceptual decisions. In agreement with previous findings, these data suggest
      that sensory evoked DA activity does not signal a stimulus physical presence but
      arises from the output of a perceptual decision.

PMID- 22626642
TI  - Heterogenous GABA(B) receptor-mediated pathways are involved in the local
      GABAergic system of the rat trigeminal ganglion: possible involvement of KCTD
      proteins.
AB  - It is well known that Gamma-aminobutyric acid (GABA) plays an important role in
      signal transduction in the central nervous system. However, the function of GABA
      in the peripheral nervous system, including sensory ganglions, is still unclear.
      In this study we have characterized the expression, cellular distribution, and
      function of GABA(B) receptor subunits, and the recently discovered GABA(B)
      auxiliary subunits, K(+) channel tetramerization domain-containing (KCTD)
      proteins, in rat trigeminal ganglion (TG) neuronal cells, which are devoid of
      synapses. We found heterogeneous expression of both GABA(B1) and GABA(B2)
      subunits, and a near-plasma membrane localization of KCTD12. In addition, we
      found that GABA(B2) subunits correlated with KCTD16. Whole-cell current-clamp
      recordings showed that responses to the GABA(B) receptor agonist, baclofen, were
      variable and both increases and decreases in excitability were observed. This
      correlated with observed differences in voltage-dependent K(+) current responses
      to baclofen in voltage-clamped TG neuronal cells. The functional diversity of the
      GABA(B)ergic regulation on the excitability of the TG neuronal cell bodies could
      be due to the heterogenous expression of KCTD proteins, and subsequent regulation
      of plasma membrane K(+) channels. Taken together with our previous demonstration
      of a local GABA(A) receptor-mediated system in rat TG, we provide an updated
      GABAergic model in the rat TG that incorporates both GABA(A)- and GABA(B)
      receptor systems.

PMID- 22626643
TI  - Anticipatory postural adjustments during step initiation: elicitation by auditory
      stimulation of differing intensities.
AB  - Step initiation is associated with anticipatory postural adjustments (APAs) that
      vary according to the speed of the first step. When step initiation is elicited
      by a "go" signal (i.e. in a reaction time task), the presentation of an
      unpredictable, intense, acoustic startling stimulus (engaging a subcortical
      mechanism) simultaneously with or just before the imperative "go" signal is able
      to trigger early-phase APAs. The aim of the present study was to better
      understand the mechanisms underlying APAs during step initiation. We hypothesized
      that the early release of APAs by low-intensity, non-startling stimuli delivered
      long before an imperative "go" signal indicates the involvement of several
      different mechanisms in triggering APAs (and not just acoustic reflexes
      triggering brainstem structures). Fifteen healthy subjects were asked to respond
      to an imperative visual "go" signal by initiating a step with their right leg. A
      brief, binaural 40, 80 or 115 dB auditory stimulus was given 1.4 s before the
      "go" signal. Participants were instructed not to respond to the auditory
      stimulus. The centre of pressure trajectory and the electromyographic activity of
      the orbicularis oculi, sternocleidomastoid and tibialis anterior muscles were
      recorded. All three intensities of the auditory stimulus were able to evoke low
      amplitude, short APAs without subsequent step execution. The louder the stimulus,
      the more frequent the elicitation. Depending on the intensity of the stimulus,
      APAs prior to step initiation can be triggered without the evocation of a startle
      response or an acoustic blink. Greater reaction times for these APAs were
      observed for non-startling stimuli. This observation suggested the involvement of
      pathways that did not involve the brainstem as a "prime mover".

PMID- 22626644
TI  - Pronociceptive effect of 5-HT(1A) receptor agonist on visceral pain involves
      spinal N-methyl-D-aspartate (NMDA) receptor.
AB  - The functional role of serotonergic 5-HT(1A) receptors in the modulation of
      visceral pain is controversial. The objective of this study was to systematically
      examine the mechanism and site of action of a selective 5-HT(1A) receptor agonist
      8-hydroxy-2-(di-n-propylamino)-tetralin (DPAT) on visceral pain. In the
      behavioral model of visceral pain, systemic injection (5-250 MUg/kg) of DPAT
      produced a significant increase in the viscero-motor response (VMR) to colorectal
      distension (CRD) and this effect was blocked by the selective 5-HT(1A) receptor
      antagonist WAY-100135 (5 mg/kg, s.c.). Similarly, intrathecal (i.t.) injection (5
      MUmol) of DPAT into the lumbo-sacral (L6-S1) spinal cord produced a significant
      increase in VMR. The administration of N-methyl D-aspartate (NMDA) receptor
      antagonist AP5 (50 MUg/kg) prior to DPAT injection completely blocked the
      pronociceptive effect of DPAT. Similarly, DPAT failed to increase VMR in rats
      chronically treated with NR1 subunit-targeted antisense oligonucleotide (ON),
      whereas the drug increased VMR in rats treated with mismatched-ON. Chronic i.t.
      injection of allylglycine (AG), a gamma-amino decarboxylase (GAD) enzyme
      inhibitor, produced significant increase in VMRs, suggesting that the inhibition
      of GABA synthesis produces pronociception. In AG-treated rats, i.t. injection of
      DPAT failed to further increase in VMR, suggesting that the DPAT action is linked
      to GABA release. Similarly, WAY-100135 failed to attenuate VMR in AG-treated
      rats, suggesting that unlike DPAT, AG action is not via the activation of 5
      HT(1A) receptors. In electrophysiology experiments, DPAT (50 MUg/kg)
      significantly increased the responses of spinal neurons to CRD, but did not
      influence the mechanotransduction property of CRD-sensitive pelvic nerve afferent
      fibers. The effect of DPAT on spinal neurons remained unaffected when tested in
      spinal-transected (C1-C2) rats. These results indicate that the 5-HT(1A) receptor
      agonist DPAT produces pronociceptive effects, primarily via the activation of
      presynaptic 5-HT(1A) receptors in GABAergic neuron to restrict GABA release and
      thereby disinhibits the excitatory glutamatergic neurons in the spinal cord.

PMID- 22626645
TI  - The differential profiles of withdrawal symptoms induced by morphine and beta
      endorphin administered intracerebroventricularly in mice.
AB  - In the present study, withdrawal symptoms induced by morphine or beta-endorphin
      administered intracerebroventricularly (i.c.v.) were compared in ICR mice.
      Naloxone (10mg/kg) was post-treated intraperitoneally (i.p.) 3h after either a
      single or repeated (1 time/day for 3 days) i.c.v. injections with opioids.
      Withdrawal symptoms such as jumping frequency, diarrhea, weight loss, rearing,
      penile licking and paw tremor were observed for 30 min immediately after naloxone
      treatment. Withdrawal symptoms (jumping, diarrhea, weight loss, rearing, penile
      licking and paw tremor) observed in the group treated with morphine was
      persistently increased during 3 days. On the other hand, withdrawal symptoms such
      as diarrhea, weight loss and rearing in beta-endorphin-treated group were
      increased after a single injection with beta-endorphin, but gradually decreased
      after the repeated injection. Furthermore, no jumping behavior, penile licking
      and paw tremor in beta-endorphin-treated group were observed throughout the whole
      period of time. In addition, the hypothalamic changes of several signal molecules
      such as pERK, pCaMK-IIalpha, c-FOS and pCREB expression were observed during the
      presence or absence of withdrawal responses induced by morphine or beta-endorphin
      administered once or repeatedly. Both hypothalamic pCaMK-IIalpha and c-FOS
      expressions were increased by naloxone treatment in acutely administered morphine
      group, whereas only pCaMK-IIalpha expression was elevated by naloxone treatment
      in repeatedly administered morphine group. In contrast with the findings in
      morphine-treated group, only pCaMK-IIalpha expression was decreased by naloxone
      treatment in repeatedly administered beta-endorphin group. Our results suggest
      that profiles of the withdrawal symptoms induced by morphine and beta-endorphin
      administered supraspinally appear to be differentially regulated. The pCaMK
      IIalpha and the c-FOS protein expression may play important roles for the
      regulation of naloxone-precipitated withdrawal symptoms such as jumping,
      diarrhea, weight loss, rearing, penile licking and paw tremor induced by morphine
      treated group, whereas the phosphorylation of hypothalamic pCaMK-IIalpha appears
      to be involved only in the regulation of naloxone-precipitated withdrawal
      symptoms such as diarrhea, weight loss and rearing in beta-endorphin-treated
      group.

PMID- 22626646
TI  - Neurobehavioral abnormalities in a brain-specific NADPH-cytochrome P450 reductase
      knockout mouse model.
AB  - The aim of the present study was to test a new hypothesis that brain cytochrome
      P450 reductase (CPR) and CPR-dependent enzymes play important roles in behavioral
      performance. A mouse model with brain neuron-specific deletion of the Cpr gene
      (brain-Cpr-null) was recently generated. Brain-Cpr-null mice and wild-type (WT)
      littermates were compared in a variety of behavioral assays. Notable differences
      were found in the exploratory behavior assay: for both males and females,
      activity in the center of the chamber was significantly higher for brain-Cpr-null
      than for WT mice on days 2 and 3 of the assay, although no significant difference
      was found between the two groups in anxiety-like behavior in the elevated zero
      maze. Furthermore, in the fear-conditioning assay, brain-Cpr-null mice exhibited
      significantly less activity suppression than did WT controls. This deficit in
      activity suppression was not accompanied by any difference between WT and brain
      Cpr-null mice in nociceptive responses to foot shocks. Abnormal activity
      suppression was also observed in both male and female brain-Cpr-null mice during
      the contextual memory test. However, in the Morris water maze assay, the brain
      Cpr-null and WT mice were indistinguishable, indicating normal spatial memory in
      the mutant mice. These data collectively indicate a novel role of the Cpr gene in
      fear conditioning and memory.

PMID- 22626647
TI  - Neonatal dexamethasone exposure down-regulates GnRH expression through the GnIH
      pathway in female mice.
AB  - Synthetic glucocorticoid (dexamethasone; DEX) treatment during the neonatal stage
      is known to affect reproductive activity. However, it is still unknown whether
      neonatal stress activates gonadotropin-inhibitory hormone (GnIH) synthesizing
      cells in the dorsomedial hypothalamus (DMH), which could have pronounced
      suppressive action on gonadotropin-releasing hormone (GnRH) neurons, leading to
      delayed pubertal onset. This study was designed to determine the effect of
      neonatal DEX (1.0mg/kg) exposure on reproductive maturation. Therefore, GnRH,
      GnIH and GnIH receptors, G-protein coupled receptors (GPR) 147 and GPR74 mRNA
      levels were measured using quantitative real-time PCR in female mice at postnatal
      (P) days 21, 30 and in estrus stage mice, aged between P45-50. DEX-treated
      females of P45-50 had delayed vaginal opening, and irregular estrus cycles and
      lower GnRH expression in the preoptic area (POA) when compared with age-matched
      controls. The expression levels of GPR147 and GPR74 mRNA in the POA increased
      significantly in DEX-treated female mice of P21 and P45-50 compared to controls.
      In addition, GPR147 and GPR74 mRNA expression was observed in laser captured
      single GnRH neurons in the POA. Although there was no difference in GnIH mRNA
      expression in the DMH, immunostained GnIH cell numbers in the DMH increased in
      DEX-treated females of P45-50 compared to controls. Taken together, the results
      show that the delayed pubertal onset could be due to the inhibition of GnRH gene
      expression after neonatal DEX treatment, which may be accounted for in part by
      the inhibitory signals from the up-regulated GnIH-GnIH receptor pathway to the
      POA.

PMID- 22626648
TI  - Distribution and localisation of Galpha proteins in the rostral ventrolateral
      medulla of normotensive and hypertensive rats: focus on catecholaminergic
      neurons.
AB  - About 860 G-protein-coupled receptors (GPCRs) mediate their actions via
      heterotrimeric G-proteins. Their activation releases Galpha from Gbetalambda
      subunits. The type of Galpha subunit dictates the major signalling proteins
      involved: adenylyl cyclase, PLC and rhoGEF. The rostral ventrolateral medulla
      (RVLM), containing the rostral C1 (rC1) cell group, sets and maintains the tonic
      and reflex control of blood pressure and a plethora of inputs converge onto these
      neurons. We determined the relative abundance of 10 Galpha subunit mRNAs,
      representing the four major families, within the RVLM, using quantitative RT-PCR.
      In situ hybridisation (ISH) combined with immunohistochemistry (IHC) was used to
      quantify and compare this expression in rC1 with that in the A1 and A5 cell
      groups. The relative abundance of Galpha subunit mRNAs and a comparison of gene
      expression levels were quantitatively determined in normotensive and hypertensive
      rat strains. All 10 Galpha mRNAs were detected in the RVLM of Sprague-Dawley (SD)
      rats with relative abundance such that
      Galphas>Galphai2>Galphao>Galphaq>GalphaL>Galpha11>Galphai3>Galphai1>Galpha12>Galp
      a13. The high abundance of Galpha mRNAs signalling via adenylyl cyclase indicates
      the importance of associated GPCRs. Within the rC1 and A1 groups similar
      differential Galpha mRNA expression profiles were seen with Galphas being found
      in all rC1 cells, Galpha11 absent and Galphai3 rarely expressed. Thus
      functionally distinct subgroups exist within the rC1 and A1 cell groups as
      differing distributions of Galpha subunits must reflect the array of GPCRs that
      influence their activity. In contrast, all A5 cells expressed all Galpha mRNAs
      suggesting a functionally homogeneous group. When the 10 Galpha mRNAs of the RVLM
      in spontaneously hypertensive rats (SHR) were compared quantitatively to Wistar
      Kyoto (WKY), only Galphas and Galpha12 were significantly elevated. However when
      the expression in normotensive SD and WKY was compared with SHR no significant
      differences were evident. These findings demonstrate a range of GPCR signalling
      capabilities in brainstem neurons important for homeostasis and suggest a
      prominent role for signalling via adenylyl cyclase.

PMID- 22626650
TI  - The social defeat animal model of depression shows diminished levels of orexin in
      mesocortical regions of the dopamine system, and of dynorphin and orexin in the
      hypothalamus.
AB  - Anhedonia is a core symptom of clinical depression. Two brain neuropeptides that
      have been implicated in anhedonia symptomology in preclinical depression models
      are dynorphin and orexin; which are concentrated along lateral hypothalamic
      dopamine reward pathways. These affect regulating neuropeptides modulate each
      other's function, implicating an interactive dysfunction between them in
      anhedonia symptomology. But whether their influences are modified or imbalanced
      within the hypothalamus or dopamine system in anhedonic preclinical depression
      models is not yet clear. We used radioimmunoassay to determine this in the rat
      social defeat model of depression; at a time that anhedonic sexual disinterest
      was expressed. In tissue samples of the medial prefrontal cortex (mPFC), ventral
      tegmental area (VTA) and nucleus accumbens, basal dynorphin levels were similar
      to normal animals. But orexin was reduced in the VTA and mPFC. Also, dynorphin
      and orexin were both diminished in the hypothalamus which is noteworthy since
      nearly all hypothalamic orexin cells co-express dynorphin. These findings suggest
      that orexin and dynorphin function may be imbalanced between the hypothalamus and
      mesocortical dopaminergic brain regions in depression.

PMID- 22626651
TI  - [Comparative analysis of mice models for preeclampsia].
AB  - Preeclampsia is a multifactorial disease of pregnancy. It is a major cause of
      maternal and perinatal mortality and morbidity and is defined by the de novo
      onset of hypertension and proteinuria after the 20th week of pregnancy. This
      pathology manifests during the early stages of pregnancy, making it hard to
      predict and very difficult to study in humans (presymptomatic phase and lack of
      tissues access). Animal models are therefore necessary to study the
      physiopathology of preeclampsia, however, since this pathology is specifically
      human, there are no spontaneous models. Animal models have thus been engineered.
      In this review, the models obtained in mice are described and compared. These
      models are essential for the development of new therapeutic strategies.

PMID- 22626649
TI  - Lectican proteoglycans, their cleaving metalloproteinases, and plasticity in the
      central nervous system extracellular microenvironment.
AB  - The extracellular matrix (ECM) in the central nervous system actively
      orchestrates and modulates changes in neural structure and function in response
      to experience, after injury, during disease, and with changes in neuronal
      activity. A component of the multi-protein, ECM aggregate in brain, the
      chondroitin sulfate (CS)-bearing proteoglycans (PGs) known as lecticans, inhibit
      neurite outgrowth, alter dendritic spine shape, elicit closure of critical period
      plasticity, and block target reinnervation and functional recovery after injury
      as the major component of a glial scar. While removal of the CS chains from
      lecticans with chondroitinase ABC improves plasticity, proteolytic cleavage of
      the lectican core protein may change the conformation of the matrix aggregate and
      also modulate neural plasticity. This review centers on the roles of the
      lecticans and the endogenous metalloproteinase families that proteolytically
      cleave lectican core proteins, the matrix metalloproteinases (MMPs) and a
      disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs), in neural
      plasticity. These extracellular metalloproteinases modulate structural neural
      plasticity-including changes in neurite outgrowth and dendritic spine remodeling
      and synaptic plasticity. Some of these actions have been demonstrated to occur
      via cleavage of the PG core protein. Other actions of the proteases include
      cleavage of non-matrix substrate proteins, whereas still other actions may occur
      directly at the cell surface without proteolytic cleavage. The data convincingly
      demonstrate that metalloproteinases modulate physiological and pathophysiological
      neural plasticity.

PMID- 22626652
TI  - [Ischemic stroke. Prevalence of cardiovascular causes documented by an extensive
      cardiovascular workup in 110 patients].
AB  - PURPOSE: The ischemic cerebrovascular accidents (I CVA) correspond to a pathology
      widely dominated by atherosclerosis and embolic cardiopathies. Our work aimed to
      determine the frequency of the cardiovascular diseases among the patients who
      were previously victims of an I CVA and the interest of the cardiovascular
      assessment in the etiologic inquest. PATIENTS AND METHODS: We led a retrospective
      study in the cardiology service of the Avicenne military hospital of Marrakech
      about 110 cases of I CVA between January 2005 and August 2008. The
      electrocardiogram (ECG), Holter ECG, transthoracic echocardiography and Doppler
      echography of the cervical vessels were systematically made for all the patients.
      The transesophageal echocardiography was practice in a few patients. RESULTS: The
      average age of the patients was 60.8 years old (+/-12.14) with a male
      predominance (72%). Ninety-one percent of the patients presented at least one
      cardiovascular risk factor: hypertension (66.45%), diabetes (41.8%), smoking
      (35.45%). Cardiovascular antecedents were noted among 18.2% of the patients, the
      continuous atrial fibrillation comes first (9%). A carotid atheromatous excess
      was noted in 74 cases of which 24 with a significant plaque. The transesophageal
      echocardiography made to 13 patients showed a spontaneous echo contrast with a
      left atrial thrombus in four cases and a left atrial myxoma in one patient.
      CONCLUSION: Penetrating artery disease occupies 39%, large artery atherosclerosis
      28% and cardiogenic stroke 18%. The cardiovascular assessment is indispensable,
      and the echocardiography is more interesting in presence of cardiopathy. Its
      therapeutic repercussion is modest.

PMID- 22626653
TI  - Carnosine analogues containing NO-donor substructures: synthesis, physico
      chemical characterization and preliminary pharmacological profile.
AB  - The synthesis, physico-chemical, and biological characterisation of a short
      series of carnosine amides bearing NO-donor nitrooxy functionalities are
      described. The NO-donor carnosine analogues and their des-NO derivatives display
      carnosine-like properties, differing from the lead for their high serum
      stability. The newly-synthesised compounds are able to complex Cu(2+) ions at
      physiological pH, displaying significant copper ion sequestering ability, and
      protect LDL from oxidation catalysed by Cu(2+) ions. All products show moderately
      potent HNE quenching activity. The NO-donor compounds 7c-f relaxed rat aorta
      strips via an NO-dependent mechanism. In vivo evaluation of organ protection in a
      model of cerebral ischaemia/reperfusion injury, using the selected NO-donor 7e
      and its des-NO analogue 7a, showed that both derivatives protect from hypoxia
      induced brain damage, at lower concentrations than carnosine; 7e also decreased
      serum TNF-alpha levels. This class of NO-donor carnosine amides is worthy of
      further study as potential tools for treating a wide range of chronic vascular
      and neurodegenerative diseases in which NO-bioavailability is reduced.

PMID- 22626654
TI  - Synthesis, crystal structures and electronic properties of isomers of chloro
      pyridinylvinyl-1H-indoles.
AB  - Three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and
      tested as inhibitors of human tryptophan 2,3-dioxygenase (hTDO). The crystal
      structures of two of them were solved by X-ray diffraction. The solubility of the
      molecules also was determined experimentally. The molecular electrostatic
      potentials and dipole moments of the three isomers were calculated by ab initio
      quantum mechanics (HF/6-311G). The single crystal X-ray analyses reveal non
      planar structures. This non-coplanarity is retained during docking of the
      compounds into a model of hTDO, the molecular target of this series. The position
      of the Cl atom does not significantly affect the electronic delocalization.
      Nevertheless, the position of the Cl atom produces a local variation of bond
      lengths inducing different dipole moments for these isomers. Variations in dipole
      moments are consistent with the different melting points and crystal packings.
      Differences in aqueous solubilities are best explained by subtle changes in H
      bonds resulting from different accessibilities of the indole NH's due to steric
      effects of the Cl substituent. The non-coplanarity plays an important role in the
      crystalline packing of the molecules in contrast to the position of the Cl. This
      study leads to a better understanding of the structural and electronic
      characteristics of this chemical series and can potentially help to better
      understand their inhibitory activity.

PMID- 22626655
TI  - Endothelial progenitor cell and adhesion molecules determine the quality of the
      coronary collateral circulation/Endothelial progenitor cells (CD34+KDR+) and
      monocytes may provide the development of good coronary collaterals despite the
      vascular risk factors and extensive atherosclerosis.

PMID- 22626656
TI  - Echocardiographic measurement of epicardial fat thickness: in search for a
      consensus/Correlation of echocardiographic epicardial fat thickness with severity
      of coronary artery disease-an observational study.

PMID- 22626657
TI  - [Percutaneous renal denervation in patients with resistant hypertension-first
      experiences in Turkey].

PMID- 22626658
TI  - Can an observational case-controlled study assess survival benefits in a group of
      patients undergoing CABG or medical treatment sufficiently?/ Survival of patients
      with well-developed collaterals undergoing CABG or medical treatment: an
      observational case-controlled study.

PMID- 22626659
TI  - [The importance of right ventricular failure in pulmonary embolism/Clinical,
      laboratory and computerized tomography pulmonary angiography (CTPA) results in
      pulmonary embolism: retrospective evaluation of 205 patients].

PMID- 22626660
TI  - [Description of a valve/The effects of implanted valve sizes on ventricular
      hypertrophy in aortic stenosis].

PMID- 22626661
TI  - Hypothyroidism leading to a syncopal episode: a reminder to check drug
      interactions/A case of iatrogenic hypothyroidism presented with cardio-inhibitory
      syncope and resolved by thyroxine supplementation.

PMID- 22626662
TI  - [Ventricular pacing through coronary sinus in a patient with a prosthetic
      tricuspid valve].

PMID- 22626663
TI  - The role of real-time 3-dimensional transesophageal echocardiography in depiction
      of the concealed base of the iceberg.

PMID- 22626664
TI  - A parachute mitral valve accompanying persistent left superior vena cava:
      assessment by three-dimensional transthoracic echocardiography.

PMID- 22626665
TI  - Pseudocirrhosis; constrictive pericarditis due to huge calcific pericardial
      cystic mass compressing right cardiac chambers.

PMID- 22626666
TI  - Ruptured covered stent in a ruptured coronary artery: a catheterization
      laboratory nightmare.

PMID- 22626667
TI  - ["Spinning wheels'' syndrome].

PMID- 22626668
TI  - Black aorta in a patient with alkaptonuric ochronosis.

PMID- 22626669
TI  - Chest X-ray in  a hypertensive patient with stage 2 diastolic dysfunction.

PMID- 22626670
TI  - [On medical treatment vs revascularization, subscription, the Anatolian Journal
      of Cardiology awards, remembering Dr. Ersin].

PMID- 22626671
TI  - Addressing trauma in collaborative mental health care for refugee children.
AB  - Primary care institutions, including clinics, schools and community
      organizations, because of their closeness to the family living environment, are
      often in a privileged position to detect problems in traumatized refugee children
      and to provide help. In a collaborative care model, the child psychiatrist
      consultant can assist the primary care consultee and family in holding the trauma
      narrative and organizing a safe network around the child and family. The
      consultant can support the establishment of a therapeutic alliance, provide a
      cultural understanding of presenting problems and negotiate with the consultee
      and the family a treatment plan. In many settings, trauma focused psychotherapy
      may not be widely available, but committed community workers and primary care
      professionals may provide excellent psychosocial support and a forum for empathic
      listening that may provide relief to the family and the child.

PMID- 22626672
TI  - Anti Propionibacterium acnes activity of rhodomyrtone, an effective compound from
      Rhodomyrtus tomentosa (Aiton) Hassk. leaves.
AB  - Propionibacterium acnes have been recognized as one of the main causative agents
      in pathogenesis of acne. Twenty one isolates of P. acnes isolated from acne
      lesions were screened for lipase and protease activity which are reported to be
      associated in acne and inflammation. Interestingly, all P. acnes isolates
      demonstrated lipase activity. Similarly, 90% of test P. acnes produced protease
      enzyme. Antibacterial activity of the ethanol extract of Rhodomyrtus tomentosa
      (Aiton) Hassk. leaves and rhodomyrtone, its principle compound were tested
      against P. acnes using broth macrodilution method. The MIC(90) values of the
      ethanol extract and rhodomyrtone were 32 and 0.5 MUg/mL, respectively. The
      numbers of the bacterial cells were reduced at least 99% after treatment with the
      ethanol extract and rhodomyrtone within 72 and 24 h, respectively. Cytotoxicity
      test of the extract and rhodomyrtone was performed on human normal fibroblast.
      The IC(50) values of the ethanol extract and rhodomyrtone were 476 and more than
      200 MUg/mL, approximately 15 and 400 folds higher than the MIC(90) values
      indicating that both substances were very low cytotoxic which could be applied as
      topical therapeutic anti-acne agents.

PMID- 22626673
TI  - [Non-invasive mechanical ventilation in out-of-hospital emergency departments].

PMID- 22626674
TI  - [Familial gastrointestinal stroma tumor due to mutation in exon 13 (K642E) of the
      KIT gene].

PMID- 22626675
TI  - A randomised, single-blind, dose-range study to assess the immunogenicity and
      safety of a cell-culture-derived A/H1N1 influenza vaccine in adult and elderly
      populations.
AB  - BACKGROUND: Modern cell-culture production techniques and the use of adjuvants
      helps to ensure that the global demand for pandemic influenza vaccine can be met.
      This study aimed to assess the immunogenicty and safety profiles of various cell
      culture-derived A/H1N1 pandemic vaccine formulations in healthy adult and elderly
      subjects. METHODS: Adult (18-60 years) subjects (n=544) received vaccine either
      containing 3.75 MUg of antigen with half the standard dose of MF59 (Novartis
      Vaccines and Diagnostics) adjuvant, 7.5 MUg antigen with a full dose of MF59, or
      a non-adjuvanted vaccine containing 15 MUg of antigen. Elderly (>= 61 years)
      subjects (n=268) received either the 3.75 MUg or 7.5 MUg adjuvanted formulations.
      Two priming vaccine doses were administered 3 weeks apart, followed by a single
      booster dose of seasonal influenza vaccine 1 year later. Immunogenicity was
      assessed 3 weeks after each vaccination. The safety profile of each formulation
      was evaluated throughout the study. RESULTS: A single primary dose of each A/H1N1
      vaccine formulation was sufficient to meet all three European (CHMP) licensure
      criteria for pandemic influenza vaccines in adult subjects. Two licensure
      criteria were met after one vaccine dose in elderly subjects; two primary doses
      were required to meet all three criteria in this age group. The highest antibody
      titres were observed in response to the 7.5 MUg vaccine containing a full dose of
      MF59 adjuvant. All subjects rapidly generated seroprotective antibody titres in
      response to booster vaccination. CONCLUSION: This study identified one 3.75 MUg
      vaccine dose containing half the standard dose of MF59 adjuvant as optimal for
      adults, two doses were optimal for elderly subjects. The antigen-sparing
      properties of MF59, and rapid, modern, cell-culture production techniques
      represent significant steps towards meeting the global demand for influenza
      vaccine.

PMID- 22626676
TI  - Unexpected and asymptomatic lingual thyroid as a cause of difficult intubation.

PMID- 22626677
TI  - Use of an intravascular warming catheter to maintain normothermia during flap
      reconstruction of the sternum.

PMID- 22626678
TI  - Use of the Trachlight in securing the airway due to accidental dislodgement of a
      tracheostomy tube.

PMID- 22626679
TI  - Oculocardiac reflex elicited during debridement of an empty orbit.

PMID- 22626680
TI  - A rapid emergence device to aid recovery from a volatile anesthetic in stage II
      nasal reconstruction repair.

PMID- 22626682
TI  - Reflux-preventing face mask designed for painless gastroscopy.

PMID- 22626681
TI  - Preoperative moderate renal impairment is an independent risk factor of
      transfusion in elderly patients undergoing hip fracture surgery and receiving low
      molecular-weight heparin for thromboprophylaxis.
AB  - STUDY OBJECTIVE: To define the risk factors of allogeneic erythrocyte transfusion
      in patients older than 65 years of age who underwent hip fracture surgery.
      DESIGN: Retrospective, single-center study. SETTING: Orthopedic unit of a
      university hospital. MEASUREMENTS: The records of 413 consecutive patients
      undergoing hip fracture surgery over a 12-month period and receiving low
      molecular-weight heparin (LMWH) for thromboprophylaxis were retrospectively
      reviewed. Preoperative independent predictors of transfusion were determined by
      multivariate analysis, from which a model of individual probability of
      transfusion was derived using creatinine clearance calculated by Cockroft-Gault
      (CG) and the Modification of Diet in Renal Disease (MDRD) formulas. MAIN RESULTS:
      Using the CG and MDRD formulas, 56.9% and 50.1% of patients had moderate renal
      impairment that was an independent factor associated with transfusion, with
      adjusted odds ratios of 2.44 (1.49 - 4.02) and 2.35 (1.32 - 4.18), respectively.
      Other factors were fracture with trochanteric extension, preoperative hemoglobin
      (Hb) < 12 g/dL, and weight. The observed transfusion rate and probability of
      transfusion calculated with the regression logistic model were well correlated: y
      = 0.9534x + 0.0287, P < 0.0001, Pearson coefficient 0.988, goodness of fit,
      chi(2), P = 1 with CG; y = 0.9197x + 0.0504, P < 0.0001, Pearson coefficient
      0.956, goodness of fit, chi(2), P = 1 with MDRD). CONCLUSION: This predictive
      model may be useful to identify those elderly patients undergoing hip fracture
      repair who are at risk of blood transfusion.

PMID- 22626683
TI  - Performance of three new-generation pulse oximeters during motion and low
      perfusion in volunteers.
AB  - STUDY OBJECTIVE: To evaluate pulse oximeter performance during motion and induced
      low perfusion in volunteers. DESIGN: Prospective volunteer study. SETTING: Direct
      Observation unit. SUBJECTS: 10 healthy adult volunteers. INTERVENTIONS: Ten
      volunteers were monitored with three different pulse oximeters while they
      underwent desaturation to about 75% oxygen saturation (SpO(2)) and performed
      machine-generated (MG) and volunteer-generated (VG) hand movements with the test
      hand, keeping the control hand stationary. MEASUREMENTS: SpO(2) and pulse rate
      readings from the motion (test) and stationary (control) hands were recorded as
      well as the number of times and the duration that the oximeters connected to the
      test hands did not report a reading. Sensitivity, specificity, performance index
      for SpO(2), and pulse rate (PR) were calculated for each pulse oximeter by
      comparing performance of the test hand with the control hand. MAIN RESULTS:
      During both MG and VG motion, the Masimo Radical had higher SpO(2) specificity
      (93% and 97%) than the Nellcor N-600 (67% and 77%) or the Datex-Ohmeda TruSat
      (83% and 82%). The Masimo Radical also had higher SpO(2) sensitivity (100% and
      95%) than the Nellcor N-600 (65% and 50%) or the Datex-Ohmeda TruSat (20% and
      15%) during both MG and VG motion. During MG motion, the Masimo Radical had the
      lowest PR failure rate (0%) compared with the Nellcor N-600 (22.2%) and Datex
      Ohmeda TruSat (1.3%). However, during VG motion, the Masimo Radical had the
      lowest SpO(2) failure rate (0%) of the three devices (Nellcor N-600 16.4% and
      Datex-Ohmeda TruSat 1.7%). Both the Masimo Radical and the Datex-Ohmeda TruSat
      had lower PR failure rates (0% and 4.4%) than the Nellcor N-600 (33.9%). There
      were no significant differences in SpO(2) or PR performance index between the
      three devices. CONCLUSIONS: The Masimo Radical had higher SpO(2) sensitivity and
      specificity than the Nellcor N-600 and Datex-Ohmeda TruSat during conditions of
      motion and induced low perfusion in this volunteer study.

PMID- 22626684
TI  - Femoral nerve catheter-induced neuralgia.

PMID- 22626685
TI  - Bulk oxygen tank vaporizer leak.

PMID- 22626686
TI  - Delayed presentation: negative pressure pulmonary hemorrhage.
AB  - Negative pressure pulmonary hemorrhage (NPPH) is a rare, life-threatening
      complication that develops after an acute upper airway obstruction. A 26 year
      old, healthy African-American man with no underlying lung disease developed
      negative pressure pulmonary edema and subsequently NPPH during recovery from
      general anesthesia for elective spine surgery. Diagnostic bronchoscopy confirmed
      an alveolar source of the bleeding. Clinical improvement was quick with
      supportive care in the medical intensive care unit.

PMID- 22626687
TI  - Abnormal coagulation profile after hepatic resection: the effect of chronic
      hepatic disease and implications for epidural analgesia.
AB  - STUDY OBJECTIVE: To evaluate the effect of chronic hepatic disease on
      postoperative coagulation. DESIGN: Retrospective cohort study. SETTING: Operating
      room with postoperative inpatient followup. MEASUREMENTS: The records of 153
      patients who underwent elective open hepatic resection were reviewed. The
      perioperative coagulation profile of each patient was assessed. The postoperative
      period was subdivided into the early [postoperative day (POD) 0-3] and late (POD
      4 - POD 7) periods. MAIN RESULTS: 68 (44.4%) patients had chronic hepatic disease
      and 50 (32.7%) had cirrhosis. Eighty-four (54.9%) patients had an abnormal early
      postoperative coagulation profile and 46 (30.1%) had an abnormal late
      postoperative coagulation profile. The proportion of patients having an abnormal
      coagulation profile peaked on POD 2, at 39.2%. Only 5.3% of patients had an
      abnormal coagulation profile on POD 7. The independent predictors of abnormal
      early and late postoperative coagulation profiles were preexisting hepatic
      cirrhosis [early: odds ratio (OR) 3.73(1.49 - 9.29), late: OR 6.84(2.11 -
      22.21)], abnormal preoperative coagulation profile [early: OR 9.68 (1.97 - 47.5),
      late: OR 11.71 (3.61- 38.02)], major hepatic resection [early: OR 4.15 (1.66 -
      10.4), late: OR 5.43 (1.68 - 17.47)], and intraoperative blood loss. CONCLUSIONS:
      An abnormal postoperative coagulation profile after hepatic surgery is common in
      a patient population with chronic hepatic disease.

PMID- 22626688
TI  - Pneumocephalus with BiPAP use after transsphenoidal surgery.
AB  - While the benefits of continuous positive airway pressure (CPAP) or bilevel
      positive airway pressure (BiPAP) for patients with obstructive sleep apnea are
      well described, reports in the literature of complications from its use are rare.
      A patient who received postoperative BiPAP after undergoing transsphenoidal
      craniopharyngioma resection developed severe pneumocephalus and unplanned
      intensive care unit admission. Although the pneumocephalus resolved with
      conservative management over two weeks, we propose caution in the use of CPAP
      postoperatively in patients undergoing procedures of the head and neck.

PMID- 22626689
TI  - Early echocardiographic detection of a massive intracardiac thrombus in a patient
      scheduled for orthotopic liver transplantation.
AB  - Transesophageal echocardiography (TEE) in cases of orthotopic liver
      transplantation is gaining acceptance for intraoperative hemodynamic monitoring.
      The timepoint of TEE probe insertion varies and is based on the fear of bleeding
      complications in the setting of portal hypertension with esophageal varices. In
      this case, early insertion of the TEE probe and examination resulted in the early
      detection of a large intracardiac thrombus, and thus the cancellation of the
      planned procedure. This case highlights the potential value of early TEE
      examination in orthotopic liver transplantation.

PMID- 22626690
TI  - The next generation of therapies for adrenocortical cancers.
AB  - Adrenocortical carcinoma (ACC) is a rare cancer for which few treatment options
      have been available. Currently, the best available treatment involves combination
      chemotherapy with the adrenolytic drug mitotane, although the response rate
      remains modest. Over the past 10 years there has been renewed interest in the
      field owing to the recognition that targeted therapies may provide new avenues
      for effective treatment of this deadly disease. Molecular analyses have revealed
      specific signaling alterations in ACC, and advances in drug development have
      generated the tools to block these pathways. Although convincing evidence for the
      effectiveness of targeted therapies is not currently available, these studies are
      in progress and should shift the prognosis of this disease in the years to come.

PMID- 22626691
TI  - Integrin alpha5beta1 simultaneously controls EGFR-dependent proliferation and Akt
      dependent pro-survival signaling in epidermoid carcinoma cells.
AB  - To delineate distinctive role of the components of alpha5beta1 integrin-EGFR axis
      in control of epidermoid carcinoma cell proliferation, we performed individual
      inhibition of alpha5beta1 and EGFR via genetic and phamacological methods,
      respectively. We demonstrated that pharmacological inhibition of epidermal growth
      factor receptor (EGFR) significantly affected proliferation of A431 human cells
      by inducing the G0/G1 cell cycle arrest, whereas shRNA-mediated depletion of
      alpha5 subunit of alpha5beta1 integrin led to a similar type of cell cycle arrest
      followed by significant apoptosis. Both treatments resulted in suppression of
      activated (phosphorylated) forms of focal adhesion kinase (FAK) and Erk. However,
      unlike EGFR inhibition, depletion of alpha5 led to substantial suppression of AKT
      activity. Accordingly, pharmacological inhibition of EGFR and AKT recapitulated
      detrimental effects caused by shRNA-mediated depletion of alpha5. Moreover,
      depletion of alpha5 led to a severe drop in the amounts of active EGFR. Thus, for
      the first time, we demonstrated that alpha5beta1 integrin simultaneously
      maintains pro-survival signaling via continuous activation of AKT and up
      regulates proliferation via activation of EGFR.

PMID- 22626692
TI  - Multi-drug-resistant central nervous system tuberculosis.

PMID- 22626693
TI  - An initial experience with therapeutic drug monitoring of levetiracetam as
      reported from a pediatric clinical setting in India.
AB  - BACKGROUND AND OBJECTIVES: Monitoring of levetiracetam in routine clinical
      practice is not strongly recommended. The aim of this study was to investigate
      any difference in serum levetiracetam concentration between patients on enzyme
      inducing and -inhibiting antiepileptic co-medication and also to identify any
      correlation between levetiracetam concentration and clinical response. MATERIALS
      AND METHODS: This study included pediatric patients with epilepsy from a tertiary
      care referral hospital in India. Details of antiepileptic co-medication, seizure
      frequency before and after initiating levetiracetam were recorded. Serum trough
      levetiracetam concentration was measured. RESULTS: Of the 69 children recruited
      in the study, 55 children had >50% reduction in seizure frequency compared to
      baseline seizure frequency. Eight patients showed no improvement. The serum
      concentration of levetiracetam was more than 10 MUg/ml in 78.2% of responders and
      75% non-responders. There was no difference in dosing between responders and non
      responders. Patients on enzyme-inducing co-medication had lower median serum
      levetiracetam concentrations (7.3 MUg/ml) compared to those on enzyme-inhibiting
      co-medication (14.4 MUg/ml) or those without interfering antiepileptic co
      medication (16.6 MUg/ml). CONCLUSION: Levetiracetam monitoring has a role in
      patients on antiepileptic polypharmacy and for confirmation of compliance.

PMID- 22626694
TI  - Clinical predictors of mechanical ventilation in Guillain-Barre syndrome.
AB  - BACKGROUND: Patients with Guillain-Barre syndrome (GBS) require assisted
      ventilation frequently. However, no single factor can predict ventilator
      requirement. AIMS: To identify clinical variables which could predict the need
      for mechanical ventilation in GBS. SETTINGS AND DESIGN: Tertiary hospital-based
      retrospective and prospective study. MATERIALS AND METHODS: One hundred and
      thirty-eight GBS patients studied were divided into two groups ventilated (Group
      1) and non-ventilated (Group 2). Parameters assessed included age, gender,
      associated illness(es), antecedent events, first symptom at onset, time from
      onset to bulbar involvement, confinement to bed and peak disability, upper limb
      power and reflexes at nadir, presence of facial weakness, neck muscle weakness
      and autonomic dysfunction. STATISTICAL ANALYSIS: Multivariate predictors of
      ventilation were assessed using logistic regression analysis. RESULTS: There were
      53 patients in Group 1 and 85 in Group 2. The mean age in the two groups was
      comparable. On bivariate analysis, simultaneous weakness of upper (UL) and lower
      (LL) limbs as the initial symptom (P<0.001); UL power less than Grade 3/5 at
      nadir (P<0.001); presence of neck and bulbar weakness (P<0.001); shorter duration
      from onset to bulbar weakness and confinement to bed (P=0.001) and bilateral
      facial involvement (P<0.01) were more frequently associated with the need for
      ventilation. Preserved reflexes in UL at nadir was significantly associated with
      absence of the need for mechanical ventilation (P<0.01). On multivariate
      analysis, factors independently associated with the need for mechanical
      ventilation included simultaneous motor weakness in UL and LL as the initial
      symptom (P=0.02), UL power<3/5 (Medical Research Council grade) at nadir
      (P=0.013) and presence of bulbar weakness (P<0.001). Preserved reflexes in the UL
      at nadir was independently associated with a lesser need for ventilation
      (P=0.001). CONCLUSIONS: Comprehensive assessment of clinical features may predict
      the need for mechanical ventilation in patients of GBS.

PMID- 22626695
TI  - Risk factors, clinical profile, and long-term outcome of 428 patients of cerebral
      sinus venous thrombosis: insights from Nizam's Institute Venous Stroke Registry,
      Hyderabad (India).
AB  - BACKGROUND: With the widespread use of neuroimaging and hematological workup,
      many of the previously held concepts about cerebral sinus venous thrombosis
      (CSVT) are changing. OBJECTIVE: The objective of this study was to investigate
      the risk factors, clinical profile, and outcome of the fully investigated cases
      of CSVT from a major university referral hospital in South India. MATERIALS AND
      METHODS: Consecutive patients of CSVT confirmed by definite neuroimaging criteria
      and fully investigated for prothrombotic states, between June 2002 and September
      2010, were prospectively studied in the Venous Stroke Registry of Nizam's
      Institute of Medical Sciences, Hyderabad, South India. RESULTS: Of the 428
      patients, 230 (53.7%) were men and the mean age was 31.3 years (range 8-65
      years). Seizures were noted in 126 (29.4%) patients, stroke like presentation was
      found in 122 (28.5%) patients, and benign intracranial hypertension like
      presentation was found in 78 (18.2%) patients. Common risk factors were anemia in
      79 (18.4%), hyperhomocysteinemia in 78 (18.2%), alcoholism in 67 (15.6%), oral
      contraceptive pill intake in 49 (11.4%), postpartum state in 42 (9.8%),
      anticardiolipin antibodies in 31 (7.2%), and protein S deficiency in 53 (12.3%)
      patients. Good outcome at 90 days (modified Rankin Scale L 2) was observed in 273
      (71.2%) of 383 patients available for follow-up. In-house mortality was noted in
      33 (7.7%) and recurrence in 22 (5.1%) patients. CONCLUSIONS: Compared to the
      previous studies, prevalence of CSVT was higher in men. Anemia,
      hyperhomocysteinemia, alcoholism, oral contraceptive use, and postpartum state
      were the most common risk factors. Overall prognosis was good, but a small
      percentage of patients died or showed recurrence.

PMID- 22626696
TI  - 'Susceptibility sign' on susceptibility-weighted imaging in acute ischemic
      stroke.
AB  - BACKGROUND AND AIM: Acute intra-arterial thrombus produces susceptibility
      artifact on gradient echo images (susceptibility sign). Our aim was to study the
      sensitivity and specificity of the susceptibility sign in various major
      intracranial arteries on susceptibility-weighted imaging (SWI) in patients with
      acute stroke. We also compared it with the 'hyperintensity sign' on fluid
      attenuated inversion recovery (FLAIR) and 'hyperdense artery sign' on computed
      tomography (CT) for middle cerebral artery (MCA) occlusion. MATERIALS AND
      METHODS: We have retrospectively studied 48 patients with ischemic stroke in
      various stages, due to intracranial arterial occlusions, for presence of
      'hyperdense artery sign' (CT), 'hyperintense arterial sign' (FLAIR sequence) and
      'susceptibility sign' (SWI). The sensitivity and specificity of each sign to
      detect intracranial arterial occlusion were calculated using the contrast
      enhanced magnetic resonance (MR) angiogram as reference standard. RESULTS: The
      sensitivity and specificity of the 'susceptibility sign' for detecting the MCA
      occlusion were 77% and 100% respectively (10 of 13).The sensitivity of the
      'susceptibility sign' for detecting anterior cerebral artery (ACA) occlusion was
      50% (1 of 2), 66.6% for posterior cerebral artery (2 of 3) and 75% for basilar
      artery (3 of 4). All the vertebral artery occlusions showed 'susceptibility sign'
      (6 of 6). Overall sensitivity and specificity of the 'susceptibility sign' for
      all acute major intracranial arterial occlusions were 82% and 100% respectively.
      Only one of the two cases of subacute infarcts studied showed a positive
      susceptibility sign. None of the 11 chronic intracranial occlusions and seven
      internal carotid occlusions showed the sign intracranially. CONCLUSION:
      'Susceptibility sign' is more sensitive in detecting the acute MCA thrombus as
      compared to 'hyperdense MCA sign' on CT and 'hyperintense artery' sign on FLAIR
      images. It also has high sensitivity and specificity for other intracranial acute
      arterial occlusions.

PMID- 22626697
TI  - Early risk and predictors of cerebrovascular and cardiovascular events in
      transient ischemic attack and minor ischemic stroke.
AB  - BACKGROUND: Transient ischemic attack (TIA) and minor ischemic stroke (MIS) are
      associated with early recurrence and deterioration respectively. The aim of the
      present study was to assess the risk of new cerebrovascular and cardiovascular
      events in a prospective, emergently enrolled patient cohort with TIA and MIS and
      the predictors of risk. MATERIALS AND METHODS: Patients with TIA and MIS (NIH
      Stroke Scale [NIHSS] <= 5) presenting within the first 48 h between July 2008
      June 2009 were prospectively enrolled. The primary outcome was new-onset stroke,
      TIA, cardiovascular events and vascular death at 90 days and early deterioration
      in patients with minor stroke. The 90-day outcome was also assessed (excellent
      outcome; modified Rankin scale [mRS] <=2). RESULTS: Eighteen (15.3%) of the 118
      patients enrolled developed new cerebrovascular or cardiovascular events during
      the 90 days of follow-up, nine (50%) of which occurred within seven days. Of the
      all new events 5.9% (7/118) had new stroke, 4.2% (5/118) patients developed early
      deterioration, 2.5% (3/118) patients had recurrent TIA and 2.5% (3/118) had
      cardiovascular events at 90 days. Eight (6.7%) patients had poor outcome at 90
      days (mRS>2). The factors predicting new vascular events were presence of
      coronary artery disease (CAD), and stroke etiology being large artery
      atherosclerosis (LAA). CONCLUSION: In patients with TIA and MIS, despite urgent
      evaluation and aggressive management, the short-term risk of stroke and other
      vascular events is high. Those with CAD and LAA should be monitored closely for
      early deterioration.

PMID- 22626698
TI  - The etiological diagnosis and outcome in patients of acute febrile
      encephalopathy: a prospective observational study at tertiary care center.
AB  - BACKGROUND: Acute febrile encephalopathy (AFE) is a clinical term used to an
      altered mental state that either accompanies or follows a short febrile illness
      and is characterized by a diffuse and nonspecific brain insult manifested by a
      combination of coma, seizures, and decerebration. OBJECTIVE: To identify the
      etiological diagnosis and outcome in adult patients with AFE. SETTINGS AND
      DESIGN: A prospective observational study was done in patients aged 14 years or
      above who were admitted with AFE at a tertiary care center in northwest India.
      MATERIALS AND METHODS: The non-infectious causes of unconsciousness were excluded
      and then only a diagnosis of AFE was considered. Cerebrospinal fluid (CSF)
      analysis and imaging of brain was done to determine the possible etiology.
      Outcome was assessed at 1 month of follow-up after discharge by using modified
      Rankin Scale (mRS). Data were analyzed and presented as mean, median, and
      percentages. A P value of <0.05 was considered significant. RESULTS: Of the total
      120 patients studied, pyogenic meningitis was the most common cause accounting
      for 36.7%, followed by acute viral encephalitis (AVE) in 28.33% of the patients
      (Japanese B encephalitis in 12.5%, herpes simplex virus encephalitis in 3.33%,
      and other undetermined viral etiology in 12.5%). Cerebral malaria, sepsis
      associated encephalopathy (SAE), and tuberculous meningitis were diagnosed in
      21.7%, 9.17%, and 4.2% of cases, respectively. Of the total, 16 patients died, 6
      with AVE, 3 with pyogenic meningitis, 3 with cerebral malaria, and 4 with SAE.
      mRS at discharge was >3 in 14 patients with AVE (P < 0.001), and in the remaining
      it was <3. After 1 month, mRS was >3 in six patients with AVE and in the rest it
      was <=1 (P < 0.001). CONCLUSIONS: In this study, pyogenic meningitis was the
      leading cause of AFE, followed by AVE and cerebral malaria. The outcome in cases
      with AVE can be fatal or more disabling than other etiologies.

PMID- 22626699
TI  - Monitored gradual occlusion of the internal carotid artery followed by ligation
      for giant internal carotid artery aneurysms.
AB  - OBJECTIVE: To demonstrate a technique of gradual monitored occlusion of the
      internal carotid artery (ICA) followed by ligation for giant aneurysms as an
      option for balloon test occlusion followed by permanent ligation of ICA.
      MATERIALS AND METHODS: Authors retrospectively analyzed 27 patients with giant
      and complex ICA aneurysms who underwent carotid artery ligation between January
      2001 and December 2010. Clinical presentation included headache, vision loss and
      diplopia. There were 19 patients with cavernous aneurysm, 5 supraclinoid, 1
      ophthalmic, 1 petrous segment and 1 cervical segment aneurysm located
      extracranially. All demonstrated good cross-circulation. Selverstone clamp was
      used for gradual occlusion of the ICA over 72 h under closed observation in the
      intensive care unit. RESULTS: Six patients developed hemiparesis in the
      postoperative period. Improvement occurred in one patient over two to three weeks
      while the remaining five patients had residual hemiparesis. One patient developed
      malignant MCA infarct for which decompressive craniectomy had to be done. There
      was no mortality in the present series. CONCLUSIONS: Gradual monitored occlusion
      and ICA ligation may be a simple, safe alternative procedure to clipping in
      surgically inaccessible and complex aneurysms, especially for surgeons with
      limited experience. Cross circulation study is an absolute requisite for carotid
      ligation.

PMID- 22626701
TI  - Surgery for recurrent malignant gliomas: feasibility and perioperative outcomes.
AB  - BACKGROUND: Surgery for recurrent gliomas is often undertaken in select cases.
      Equivocal oncological outcomes of such surgeries are responsible for much of the
      controversy surrounding its role. Adding to the dilemma is the perceived
      increased morbidity associated with redo surgeries. Lack of studies and absence
      of uniformity in reporting outcomes is partly responsible for this. We evaluated
      our perioperative outcomes in recurrent malignant gliomas with the aim of
      documenting these objectively. MATERIALS AND METHODS: A consecutive prospectively
      maintained database was queried for all redo surgeries in malignant gliomas
      performed at our referral neuro-oncology center. Demographic, clinical, surgical,
      and perioperative details were retrieved. Perioperative outcomes were objectively
      categorized as neurological (major/minor, transient/prolonged), regional, and
      systemic complications, along with overall morbidity and mortality. A similar
      analysis was performed for all craniotomies for intra-axial tumors. RESULTS:
      Forty-one surgeries for recurrent malignant gliomas (from a database of 196
      craniotomies for all intra-axial tumors) were evaluated. Neurological worsening
      occurred in 22.2% (12.2% major), whereas 44% showed improvement in the pre
      existing deficits. Besides, regional and systemic complications occurred in 14.2%
      and 4.8%, respectively. Overall morbidity was 29.3% (major in 14.6%) and
      mortality was 2.4%. Though not significant on multivariate analysis, prior
      treatment was an important predictor of increased regional complications.
      CONCLUSIONS: Neurological morbidity after surgery for recurrent gliomas is
      acceptable. Surgery also provides a high chance of restoration of neurological
      function. Though regional complications can be significant and need to be given
      cognizance when reporting perioperative outcomes, they are not alarmingly high.
      Careful case selection can ensure optimization of these outcomes.

PMID- 22626700
TI  - Application of the Willis covered stent for the management of posttraumatic
      carotid-cavernous fistulas: an initial clinical study.
AB  - AIMS: To evaluate the feasibility of using the Willis covered stent in the
      management of patients with traumatic carotid-cavernous fistulas (CCFs).
      MATERIALS AND METHODS: Twelve consecutive patients with 14 post-traumatic CCFs
      referred for treatment with Willis covered stents were enrolled in this
      prospective study. Data on technical success, initial and final angiographic
      results, mortality, morbidity and final clinical outcome were collected. Follow-
      up was at one, three, six, and 12 months, and yearly thereafter. RESULTS:
      Deployment of covered stents was technically successful in all the patients
      without complications. One covered stent was placed in eight patients and two
      covered stents in four. Angiographic results following stent placement showed a
      complete occlusion in nine patients with 11 CCFs, and an incomplete occlusion in
      three patients. Angiographic follow-up (mean, 14.00 +/- 6.93 months; range, 6-24
      months) revealed complete occlusion and no obvious in-stent stenosis in all the
      patients. Clinical follow-up (mean, 17.75 +/- 7.05 months; range, 7-28 months)
      demonstrated full recovery in 11 patients, and improvement in one. CONCLUSION:
      This initial experience indicates that the use of the Willis covered stent is a
      feasible procedure and may be an alternative treatment option for CCFs.

PMID- 22626702
TI  - Stereoscopic virtual realistic surgical simulation in intracranial aneurysms.
AB  - BACKGROUND: Three-dimensional (3D)-computed tomographic angiography (CTA) has
      been widely used for surgical simulation of intracranial aneurysms. Stereo
      imaging technology is progressing rapidly in recent years and stereo imaging may
      make more realistic surgical simulation possible. Therefore, we aimed at the
      establishment of a technique for stereoscopic viewing of minute volume rendering
      images while pursuing a low cost. MATERIALS AND METHODS: Between January 2009 and
      June 2011, 54 patients with ruptured intracranial aneurysms were enrolled in this
      study. CTA data was transferred to the workstation equipped with image-processing
      software, and multilayer fusion images were processed by neurosurgeons. Image
      data for stereoscopic viewing of multilayer fusion image from arbitrary
      directions were collected form rotational trajectories around an aneurysm and
      were output to MPEG file. Stereoscopic viewing using MPEG data was achieved by
      the freeware named Stereo Movie Maker. Stereo viewing method using QuickTime VR
      format was also tried. RESULTS: Multilayer fusion image created from CTA data
      displayed clearly the anatomical information about not only the aneurysm but also
      the surrounding structures, such as parent artery, venous system, brain tissue,
      skull bone, and scalp. The quality of the resulting multilayer fusion image was
      suitable for surgical simulation with virtual reality. Virtual realistic surgical
      simulation became possible by the combination of minute multilayer fusion image
      and stereoscopic viewing by our method. CONCLUSIONS: Our method for stereo
      viewing of multilayer fusion images resulted in an improvement in the capability
      of diagnostic imaging and the image-guided support for neurosurgical procedures
      in intracranial aneurysm.

PMID- 22626703
TI  - Comparative study of two laminoplasty techniques: a missed opportunity.

PMID- 22626704
TI  - Central corpectomy in cervical spondylotic myelopathy: prevertebral soft tissue
      swelling.

PMID- 22626705
TI  - Surgical management of cervical spondylotic myelopathy.
AB  - Cervical spondylotic myelopathy (CSM) is emerging as the most common cause of
      spinal cord dysfunction in the elderly worldwide. In the past decade, our
      understanding of the biomechanics of the spine has improved along with advances
      in spinal instrumentation and this has led to significant changes in the surgical
      management of CSM. This review will discuss the indications, advantages and
      limitations of different operative approaches as well as the complications and
      prognosis of surgery for cervical spondylotic myelopathy. Choice of surgical
      approach for CSM should be based on the clinical and radiological characteristics
      of the individual patient and not on the preferences of the surgeon.

PMID- 22626706
TI  - Clinical outcomes of two different types of open-door laminoplasties for cervical
      compressive myelopathy: a prospective study.
AB  - BACKGROUND: Hirabayashi open-door laminoplasty is the most typical surgical
      treatment option for cervical compressive myelopathy, however, this conventional
      approach has many complications. To minimize these complications, many modified
      approaches have been devised. AIMS: To compare clinical outcomes of two different
      types of open-door laminoplasties for cervical compressive myelopathy. MATERIALS
      AND METHODS: Fifty patients (31 men and 19 women) with cervical compressive
      myelopathy were prospectively allocated to two groups, 25 patients in each group.
      Patients in Group A underwent Hirabayashi open-door laminoplasty and patients in
      Group B underwent modified instrumented approach. The following parameters were
      studied: operation time, blood loss, perioperative complications, Japanese
      Orthopedic Association (JOA) scores, axial pain, and short-form 36 (SF-36).
      Cervical lordosis was reviewed as lordotic angle, measured at C2-C7. RESULTS:
      Mean operation time and blood loss in both the groups were similar. Perioperative
      complications occurred more frequently in Group A than in Group B. Although there
      were no significant differences in postoperative JOA scores between the two
      groups, axial pain was significantly decreased in Group B at final follow-up. The
      scores of all subscales of SF-36 were higher in Group B than in Group A.
      CONCLUSION: Both the conventional and instrumented techniques provide similar
      good results but the instrumented technique provided better axial pain relief and
      lower incidence of perioperative complications.

PMID- 22626707
TI  - Temporal progression and spatial distribution of "normal" prevertebral soft
      tissue swelling following central corpectomy for cervical spondylotic myelopathy.
AB  - OBJECTIVE: To document the temporal progression and spatial distribution of
      prevertebral soft tissue swelling (PSTS) after central corpectomy (CC) and to
      determine the variables affecting its severity. BACKGROUND: The natural
      attributes of PSTS following CC for cervical spondylotic myelopathy (CSM) have
      not been characterized in literature. MATERIALS AND METHODS: PSTS was measured at
      the C2 level and midpoint of the operated segment on lateral radiographs of the
      cervical spine taken pre-operatively and post-operatively (day 0, day 3/4, day 5
      and day 6/7) in 93 patients with CSM undergoing one to three level uninstrumented
      CC. Patient's age, weight, Nurick's grade, number of corpectomy levels and
      intubation time were correlated with the PSTS. RESULTS: Proportionately, the
      swelling was maximal at the C2 level rather than at the level of CC, on all days,
      irrespective of the level of surgery. At the C2 level, the increase in PSTS was
      maximum by day 3/4 (P = 0.0001), whereas at the CC level, the PSTS continued to
      increase till day 5 (P = 0.0001). PSTS was higher in patients undergoing a three
      level CC and in those with inclusion of C4 in the CC (P = 0.002). CONCLUSION:
      Patients undergoing CC are at risk for upper airway obstruction mainly at the C2
      level in the first 3 days after surgery due to the PSTS. Those undergoing three
      level CC, or having inclusion of C4 in the CC, have a greater degree of PSTS and
      have a higher risk of post-operative airway obstruction.

PMID- 22626709
TI  - Posterior cerebral artery-posterior communicating artery (PCA-PComA) aneurysms:
      report of five cases and literature review.
AB  - Posterior cerebral artery-posterior communicating artery aneurysms are rare and
      not well documented. In this article, we report five such cases and review four
      similar cases by searching the PubMed database through the years 1980-2011 to
      study the occurrence and treatment of this rare entity.

PMID- 22626708
TI  - Chronic manganese toxicity due to substance abuse in Turkish patients.
AB  - BACKGROUND: Manganese toxicity may lead to a levodopa-resistant akinetic-rigid
      syndrome. Pathological changes occur mostly in the pallidium and stratium.
      MATERIALS AND METHODS: We report seven patients with a new form of chronic
      manganese toxicity due to long-term intravenous use of a solution consisting of
      ephedrine, acetylsalicylic acid and potassium permanganate as a psycho-stimulant,
      popularly known as "Russian Cocktail". RESULTS: The age of the patients ranged
      between 19 and 31 years, and the duration of substance abuse was between nine and
      106 months. The onset of symptoms from first use ranged seven to 35 months. The
      initial symptom was impaired speech followed by gait disturbance and
      bradykinesia. In addition to these symptoms, choreic movements, ataxia presenting
      as backward falls and dystonia were also seen. Serum and urine samples revealed
      high levels of manganese. Hyperintense lesions on T1-weighted magnetic resonance
      imaging were seen in bilateral basal ganglia and brainstem, dentate nuclei,
      features consistent with manganese intoxication. CONCLUSION: Manganese toxicity,
      which may cause a distinctive irreversible neurodegenerative disorder, can be
      seen frequently with "Russian Cocktail" abuse, a substance which can be accessed
      very easily and at a low cost.

PMID- 22626710
TI  - Multidrug-resistant tuberculous subdural empyema with secondary methicillin
      resistant Staphylococcus aureus infection: an unusual presentation of cranial
      tuberculosis in an infant.
AB  - Despite tuberculosis (TB) being endemic in many parts of the world, its
      prevalence in infancy is low. Neurotuberculosis in this age is even rarer and
      presents either as meningitis or intracranial tuberculoma on the background of
      exposure to the disease. We report occurrence of multidrug-resistant tuberculous
      subdural empyema in a three-month-old girl as the initial presenting
      manifestation of TB in the absence of any exposure to the disease. She was
      successfully managed with surgery and drugs with good outcome at 18 months.

PMID- 22626711
TI  - Isolated myelopathy probably associated with Hashimoto's disease.

PMID- 22626712
TI  - Tuberculous spinal subdural abscess in an infant with dermal sinus.

PMID- 22626713
TI  - Chronic progressive encephalopathy, intractable seizures, and neuropathy: a triad
      of neurological features in insulinoma.

PMID- 22626714
TI  - Successful mechanical thrombectomy of acute middle cerebral artery occlusion due
      to vegetation from infective endocarditis.

PMID- 22626715
TI  - Sterile hemorrhagic brain abscess in infective endocarditis.

PMID- 22626716
TI  - Posterior fossa extradural hydatid cyst with septae and calcification.

PMID- 22626717
TI  - Intratumoral hemorrhage in brainstem low-grade glioma.

PMID- 22626718
TI  - An unusual case of post-traumatic intradiploic leptomeningeal cyst and review of
      the literature.

PMID- 22626719
TI  - Neurenteric cyst of the cerebello-pontine angle in an infant presenting with
      obstructive hydrocephalus.

PMID- 22626720
TI  - Fusiform aneurysm of transverse sinus associated with growth retardation.

PMID- 22626721
TI  - Intradiploic ossified giant cavernous hemangioma of skull with a dural tail sign
      mimicking primary calvarial meningioma.

PMID- 22626722
TI  - Disseminated cranio-spinal intradural mesenchymal chondrosarcoma.

PMID- 22626723
TI  - Subdural collections complicating third ventriculostomy: over-drainage or failure
      of ventriculostomy?

PMID- 22626724
TI  - Cervical pseudomeningocele as a cause of neurological decline after posterior
      cervical spine surgery.

PMID- 22626725
TI  - Intradural thoracic disc presenting with radiculopathy.

PMID- 22626726
TI  - Intravenous cannula: a rescue tool for cerebrospinal fluid diversion.

PMID- 22626727
TI  - Partially calcified giant intracerebral hydatid cyst in a pediatric child.

PMID- 22626728
TI  - Management of upper cervical kyphosis in an adolescent with Larsen's syndrome.

PMID- 22626729
TI  - Cerebral shading sign in a giant intraparenchymal white epidermoid.

PMID- 22626730
TI  - Reversal of MRI findings following CSF drainage in idiopathic intracranial
      hypertension.

PMID- 22626731
TI  - Diagnostic utility of LightCycler SeptiFast and procalcitonin assays in the
      diagnosis of bloodstream infection in immunocompromised patients.
AB  - Sepsis is an increasingly prevalent cause of death, and management in the early
      stage is a critical issue. However, microbiological findings are generally
      obtained late during the course of the disease. In this study, we evaluated the
      clinical utility of procalcitonin (PCT) in improving the diagnosis of bloodstream
      infections and the potential utility of the SeptiFast (SF) test, a multiplex
      pathogen detection system, in the etiological diagnosis of immunocompromised
      patients. Seventy-nine hospitalized immunocompromised patients were included in
      this study. Our results demonstrate that while the PCT value correlates highly
      with sepsis, the results do not discriminate adequately enough to justify its
      independent use as a diagnostic tool. The SF test, combined with blood cultures,
      improves microbiological data in immunocompromised patients, especially in cases
      of previous antibiotic therapy and invasive fungal infection.

PMID- 22626732
TI  - Morphological changes on the intestinal mucosa in orthotopic neobladder.
AB  - INTRODUCTION: The intestinal mucosa undergoes significant atrophic changes when
      it is used to reconstruct the urinary tract. We analyzed the ultrastructural
      changes of intestinal mucosa in the orthotopic neobladder on the basis of our
      clinical experience. PATIENTS AND METHODS: Fifteen male patients with an ileal
      neobladder underwent endoscopic biopsy at different postoperative intervals.
      RESULTS: No significant changes were observed 3 months after surgery. After 6 and
      12 months, the structure of the microvilli was modified significantly. No other
      substantial changes after 24 months were observed. CONCLUSIONS: Progressive
      modifications occur in the cytoplasmic structures involved in the absorptive
      process. They do not seem to begin before 3 months and are almost totally
      completed after 1 year.

PMID- 22626733
TI  - The zinc homeostasis network of land plants.
AB  - The use of the essential element zinc (Zn) in the biochemistry of land plants is
      widespread, and thus comparable to that in other eukaryotes. Plants have evolved
      the ability to adjust to vast fluctuations in external Zn supply, and they can
      store considerable amounts of Zn inside cell vacuoles. Moreover, among plants
      there is overwhelming, but yet little explored, natural genetic diversity that
      phenotypically affects Zn homeostasis. This results in the ability of specific
      races or species to thrive in different soils ranging from extremely Zn-deficient
      to highly Zn-polluted. Zn homeostasis is maintained by a tightly regulated
      network of low-molecular-weight ligands, membrane transport and Zn-binding
      proteins, as well as regulators. Here we review Zn homeostasis of land plants
      largely based on the model plant Arabidopsis thaliana, for which our molecular
      understanding is most developed at present. There is some evidence for
      substantial conservation of Zn homeostasis networks among land pants, and this
      review can serve as a reference for future comparisons. Major progress has
      recently been made in our understanding of the regulation of transcriptional Zn
      deficiency responses and the role of the low-molecular-weight chelator
      nicotianamine in plant Zn homeostasis. Moreover, we have begun to understand how
      iron (Fe) and Zn homeostasis interact as a consequence of the chemical similarity
      between their divalent cations and the lack of specificity of the major root iron
      uptake transporter IRT1. The molecular analysis of Zn-hyperaccumulating plants
      reveals how metal homeostasis networks can be effectively modified. These
      insights are important for sustainable bio-fortification approaches. This article
      is part of a Special Issue entitled: Cell Biology of Metals.

PMID- 22626734
TI  - A microarray of ubiquitylated proteins for profiling deubiquitylase activity
      reveals the critical roles of both chain and substrate.
AB  - Substrate ubiquitylation is a reversible process critical to cellular homeostasis
      that is often dysregulated in many human pathologies including cancer and
      neurodegeneration. Elucidating the mechanistic details of this pathway could
      unlock a large store of information useful to the design of diagnostic and
      therapeutic interventions. Proteomic approaches to the questions at hand have
      generally utilized mass spectrometry (MS), which has been successful in
      identifying both ubiquitylation substrates and profiling pan-cellular chain
      linkages, but is generally unable to connect the two. Interacting partners of the
      deubiquitylating enzymes (DUBs) have also been reported by MS, although
      substrates of catalytically competent DUBs generally cannot be. Where they have
      been used towards the study of ubiquitylation, protein microarrays have usually
      functioned as platforms for the identification of substrates for specific E3
      ubiquitin ligases. Here, we report on the first use of protein microarrays to
      identify substrates of DUBs, and in so doing demonstrate the first example of
      microarray proteomics involving multiple (i.e., distinct, sequential and
      opposing) enzymatic activities. This technique demonstrates the selectivity of
      DUBs for both substrate and type (mono- versus poly-) of ubiquitylation. This
      work shows that the vast majority of DUBs are monoubiquitylated in vitro, and are
      incapable of removing this modification from themselves. This work also
      underscores the critical role of utilizing both ubiquitin chains and substrates
      when attempting to characterize DUBs. This article is part of a Special Issue
      entitled: Ubiquitin Drug Discovery and Diagnostics.

PMID- 22626735
TI  - Should measures of patient experience in primary care be adjusted for case mix?
      Evidence from the English General Practice Patient Survey.
AB  - OBJECTIVES: Uncertainties exist about when and how best to adjust performance
      measures for case mix. Our aims are to quantify the impact of case-mix adjustment
      on practice-level scores in a national survey of patient experience, to identify
      why and when it may be useful to adjust for case mix, and to discuss unresolved
      policy issues regarding the use of case-mix adjustment in performance measurement
      in health care. DESIGN/SETTING: Secondary analysis of the 2009 English General
      Practice Patient Survey. Responses from 2 163 456 patients registered with 8267
      primary care practices. Linear mixed effects models were used with practice
      included as a random effect and five case-mix variables (gender, age,
      race/ethnicity, deprivation, and self-reported health) as fixed effects. MAIN
      OUTCOME MEASURES: Primary outcome was the impact of case-mix adjustment on
      practice-level means (adjusted minus unadjusted) and changes in practice
      percentile ranks for questions measuring patient experience in three domains of
      primary care: access; interpersonal care; anticipatory care planning, and overall
      satisfaction with primary care services. RESULTS: Depending on the survey measure
      selected, case-mix adjustment changed the rank of between 0.4% and 29.8% of
      practices by more than 10 percentile points. Adjusting for case-mix resulted in
      large increases in score for a small number of practices and small decreases in
      score for a larger number of practices. Practices with younger patients, more
      ethnic minority patients and patients living in more socio-economically deprived
      areas were more likely to gain from case-mix adjustment. Age and race/ethnicity
      were the most influential adjustors. CONCLUSIONS: While its effect is modest for
      most practices, case-mix adjustment corrects significant underestimation of
      scores for a small proportion of practices serving vulnerable patients and may
      reduce the risk that providers would 'cream-skim' by not enrolling patients from
      vulnerable socio-demographic groups.

PMID- 22626736
TI  - Signal and noise: applying a laboratory trigger tool to identify adverse drug
      events among primary care patients.
AB  - BACKGROUND: The extent of outpatient adverse drug events (ADEs) remains unclear.
      Trigger tools are used as a screening method to identify care episodes that may
      be ADEs, but their value in a population with high chronic-illness burden remains
      unclear. METHODS: The authors used six abnormal laboratory triggers for detecting
      ADEs among adults in outpatient care. Eligible patients were included if they
      were >18 years, sought primary or urgent care between November 2008 and November
      2009 and were prescribed at least one medication. The authors then used the
      clinical / administrative database to identity patients with these triggers. Two
      physicians conducted in-depth chart review of any medical records with identified
      triggers. RESULTS: The authors reviewed 1342 triggers representing 622 unique
      episodes among 516 patients. The trigger tool identified 91 (15%) ADEs. Of the 91
      ADEs included in the analysis, 49 (54%) occurred during medication monitoring, 41
      (45%) during patient self-administration, and one could not be determined. 96% of
      abnormal international normalised ratio triggers were ADEs, followed by 12% of
      abnormal blood urea nitrogen triggers, 9% of abnormal alanine aminotransferase
      triggers, 8% of abnormal serum creatinine triggers and 3% of aspartate
      aminotransferase triggers. CONCLUSIONS: The findings imply that other tools such
      as text triggers or more complex automated screening rules, which combine data
      hierarchically are needed to effectively screen for ADEs in chronically ill
      adults seen in primary care.

PMID- 22626737
TI  - What stops hospital clinical staff from following protocols? An analysis of the
      incidence and factors behind the failure of bedside clinical staff to activate
      the rapid response system in a multi-campus Australian metropolitan healthcare
      service.
AB  - OBJECTIVE: To explore the causes of failure to activate the rapid response system
      (RRS). The organisation has a recognised incidence of staff failing to act when
      confronted with a deteriorating patient and leading to adverse outcomes. DESIGN:
      A multi-method study using the following: a point prevalence survey to determine
      the incidence of abnormal simple bedside observations and activation of the rapid
      response team by clinical staff; a prospective audit of all patients experiencing
      a cardiac arrest, unplanned intensive care unit admission or death over an 8-week
      period; structured interviews of staff to explore cognitive and sociocultural
      barriers to activating the RRS. SETTING: Southern Health is a comprehensive
      healthcare network with 570 adult in-patient beds across four metropolitan
      teaching hospitals in the south-eastern sector of Melbourne. MEASUREMENTS:
      Frequency of physiological instability and outcomes within the in-patient
      hospital population. Qualitative data from staff interviews were thematically
      coded. RESULTS: The incidence of physiological instability in the acute adult
      population was 4.04%. Nearly half of these patients (42%) did not receive an
      appropriate clinical response from the staff, despite most (69.2%) recognising
      their patient met physiological criteria for activating the RRS, and being
      'quite', or 'very' concerned about their patient (75.8%). Structured interviews
      with 91 staff members identified predominantly sociocultural reasons for failure
      to activate the RRS. CONCLUSIONS: Despite an organisational commitment to the
      RRS, clinical staff act on local cultural rules within the clinical environment
      that are usually not explicit. Better understanding of these informal rules may
      lead to more appropriate activation of the RRS.

PMID- 22626738
TI  - Challenges of making a diagnosis in the outpatient setting: a multi-site survey
      of primary care physicians.
AB  - BACKGROUND: Although misdiagnosis in the outpatient setting leads to significant
      patient harm and wasted resources, it is not well studied. The authors surveyed
      primary care physicians (PCPs) about barriers to timely diagnosis in the
      outpatient setting and assessed their perceptions of diagnostic difficulty.
      METHODS: Surveys of PCPs practicing in an integrated health system across 10
      geographically dispersed states in 2005. The survey elicited information on key
      cognitive failures (including in clinical knowledge or judgement) for a specific
      case, and solicited strategies for reducing diagnostic delays. Content analysis
      was used to categorise cognitive failures and strategies for improvement. The
      authors examined the extent and predictors of diagnostic difficulty, defined as
      reporting >5% patients difficult to diagnose. RESULTS: Of 1817 physicians
      surveyed, 1054 (58%) responded; 848 (80%) respondents primarily practiced in
      outpatient settings and had an assigned patient panel (inclusion sample).
      Inadequate knowledge (19.9%) was the most commonly reported cognitive factor.
      Half reported >5% of their patients were difficult to diagnose; more experienced
      physicians reported less diagnostic difficulty. In adjusted analyses, problems
      with information processing (information availability and time to review it) and
      the referral process were associated with greater diagnostic difficulty.
      Strategies for improvement most commonly involved workload issues (panel size,
      non-visit tasks). CONCLUSIONS: PCPs report a variety of reasons for diagnostic
      difficulties in primary care practice. In this study, knowledge gaps appear to be
      a prominent concern. Interventions that address these gaps as well as practice
      level issues such as time to process diagnostic information and better
      subspecialty input may reduce diagnostic difficulties in primary care.

PMID- 22626739
TI  - Design and trial of a new ambulance-to-emergency department handover protocol:
      'IMIST-AMBO'.
AB  - BACKGROUND: Information communicated by ambulance paramedics to Emergency
      Department (ED) staff during handover of patients has been found to be
      inconsistent and incomplete, and yet has major implications for patients'
      subsequent hospital treatment and trajectory of care. AIM: The study's aims were
      to: (1) identify the existing structure of paramedic-to-emergency staff handovers
      by video recording and analysing them; (2) involve practitioners in reflecting on
      practice using the footage; (3) combine those reflections with formal analyses of
      these filmed handovers to design a handover protocol; (4) trial-run the protocol;
      and (5) assess the protocol's enactment. METHOD: The study was a 'video-reflexive
      ethnography' involving: structured analysis of videoed handovers (informed by ED
      clinicians' and ambulance paramedics' comments); ED clinicians and ambulance
      paramedics viewing their own practices; and rapid at-work training and feedback
      for paramedics. A five-question pre- and post-survey measured ED triage nurses'
      perceptions of the new protocol's impact. In total, 137 pre- and post-handovers
      were filmed involving 291 staff, and 368 staff were educated in the use of the
      new protocol. RESULTS: There was agreement that Identification of the patient,
      Mechanism/medical complaint, Injuries/information relative to the complaint,
      Signs, vitals and GCS, Treatment and trends/response to treatment, Allergies,
      Medications, Background history and Other (social) information (IMIST-AMBO) was
      the preferred protocol for non-trauma and trauma handovers. Uptake of IMIST-AMBO
      showed improvements: a greater volume of information per handover that was more
      consistently ordered; fewer questions from ED staff; a reduction in handover
      duration; and fewer repetitions by both paramedics and ED clinicians that may
      suggest improved recipient comprehension and retention. CONCLUSION: IMIST-AMBO
      shows promise for improving the ambulance-ED handover communication interface.
      Involving paramedics and ED clinicians in its development enhanced the resulting
      protocol, strengthened ED clinicians' and ambulance paramedics' sense of
      ownership over the protocol and bolstered their peers' willingness to adopt it.

PMID- 22626740
TI  - An institution-wide handoff task force to standardise and improve physician
      handoffs.
AB  - BACKGROUND: Transfers of care have become increasingly frequent and complex with
      shorter inpatient stays and changes in work hour regulations. Potential hazards
      exist with transfers. There are few reports of institution-wide efforts to
      improve handoffs. METHODS: An institution-wide physician handoff task force was
      developed to proactively address issues surrounding handoffs and to ensure a
      consistent approach to handoffs across the institution. RESULTS: This report
      discusses the authors' experiences with handoff standardisation, provider
      utilisation of a new electronic medical record-based handoff tool, and
      implementation of an educational curriculum; future work in developing hospital
      wide policies and procedures for transfers; and the authors' consensus on the
      best methods for monitoring and evaluation of trainee handoffs. CONCLUSION: The
      handoff task force infrastructure has enabled the authors to take an institution
      wide approach to improving handoffs. The task force has improved patient care by
      addressing handoffs systematically and consistently and has helped create new
      strategies for minimising risk in handoffs.

PMID- 22626741
TI  - Echocardiography screening for rheumatic heart disease in Ugandan schoolchildren.
AB  - BACKGROUND: Historically, sub-Saharan Africa has had the highest prevalence rates
      of clinically detected rheumatic heart disease (RHD). Echocardiography-based
      screening improves detection of RHD in endemic regions. The newest screening
      guidelines (2006 World Health Organization/National Institutes of Health) have
      been tested across India and the Pacific Islands, but application in sub-Saharan
      Africa has, thus far, been limited to Mozambique. We used these guidelines to
      determine RHD prevalence in a large cohort of Ugandan school children, to
      identify risk factors for occult disease, and to assess the value of laboratory
      testing. METHODS AND RESULTS: Auscultation and portable echocardiography were
      used to screen randomly selected schoolchildren, 5 to 16 years of age, in
      Kampala, Uganda. Disease likelihood was defined as definite, probable, or
      possible in accordance with the 2006 National Institutes of Health/World Health
      Organization guidelines. Ninety-seven percent of eligible students received
      screening (4869 of 5006). Among them, 130 children (2.7%) had abnormal screening
      echocardiograms. Of those 130, secondary evaluation showed 72 (55.4%) with
      possible, probable, or definite RHD; 18 (13.8%) with congenital heart disease;
      and 40 (30.8%) with no disease. Echocardiography detected 3 times as many cases
      of RHD as auscultation: 72 (1.5%) versus 23 (0.5%; P<0.001). Children with RHD
      were older (10.1 versus 9.3 years; P=0.002). Most cases (98%) involved only the
      mitral valve. Lower socioeconomic groups had more RHD (2.7% versus 1.4%; P=0.036)
      and more advanced disease (64% versus 26%; P<0.001). Antistreptolysin O titers
      were elevated in children with definite RHD. CONCLUSIONS: This is one of the
      largest single-country childhood RHD prevalence studies and the first to be
      conducted in sub-Saharan Africa. Our data support inclusion of echocardiography
      in screening protocols, even in the most resource-constrained settings, and
      identify lower socioeconomic groups as most vulnerable. Longitudinal follow-up of
      children with echocardiographically diagnosed subclinical RHD is needed.

PMID- 22626742
TI  - Telemonitoring of outpatients with heart failure: a search for the holy grail?

PMID- 22626743
TI  - Remote monitoring reduces healthcare use and improves quality of care in heart
      failure patients with implantable defibrillators: the evolution of management
      strategies of heart failure patients with implantable defibrillators (EVOLVO)
      study.
AB  - BACKGROUND: Heart failure patients with implantable cardioverter-defibrillators
      (ICDs) or an ICD for resynchronization therapy often visit the hospital for
      unscheduled examinations, placing a great burden on healthcare providers. We
      hypothesized that Internet-based remote interrogation systems could reduce
      emergency healthcare visits. METHODS AND RESULTS: This multicenter randomized
      trial involving 200 patients compared remote monitoring with standard patient
      management consisting of scheduled visits and patient response to audible ICD
      alerts. The primary end point was the rate of emergency department or urgent in
      office visits for heart failure, arrhythmias, or ICD-related events. Over 16
      months, such visits were 35% less frequent in the remote arm (75 versus 117;
      incidence density, 0.59 versus 0.93 events per year; P=0.005). A 21% difference
      was observed in the rates of total healthcare visits for heart failure,
      arrhythmias, or ICD-related events (4.40 versus 5.74 events per year; P<0.001).
      The time from an ICD alert condition to review of the data was reduced from 24.8
      days in the standard arm to 1.4 days in the remote arm (P<0.001). The patients'
      clinical status, as measured by the Clinical Composite Score, was similar in the
      2 groups, whereas a more favorable change in quality of life (Minnesota Living
      With Heart Failure Questionnaire) was observed from the baseline to the 16th
      month in the remote arm (P=0.026). CONCLUSIONS: Remote monitoring reduces
      emergency department/urgent in-office visits and, in general, total healthcare
      use in patients with ICD or defibrillators for resynchronization therapy.
      Compared with standard follow-up through in-office visits and audible ICD alerts,
      remote monitoring results in increased efficiency for healthcare providers and
      improved quality of care for patients. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00873899.

PMID- 22626744
TI  - Rheumatic heart disease: the tip of the iceberg.

PMID- 22626745
TI  - Surgery for primary cardiac tumors in children: early and late results in a
      multicenter European Congenital Heart Surgeons Association study.
AB  - BACKGROUND: To evaluate indications and results of surgery for primary cardiac
      tumors in children. METHODS AND RESULTS: Eighty-nine patients aged <=18 years
      undergoing surgery for cardiac tumor between 1990 and 2005 from 16 centers were
      included retrospectively (M/F=41/48; median age 4.3 months, range 1 day to 18
      years). Sixty-three patients (68.5%) presented with symptoms. Surgery consisted
      of complete resection in 62 (69.7%) patients, partial resection in 21 (23.6%),
      and cardiac transplant in 4 (4.5%). Most frequent histotypes (93.2%) were benign
      (rhabdomyoma, myxoma, teratoma, fibroma, and hemangioma). Postoperative
      complications occurred in 29.9%. Early and late mortality were 4.5% each (mean
      follow-up, 6.3+/-4.4 years); major adverse events occurred in 28.2% of the
      patients; 90.7% of patients are in New York Heart Association class I. There were
      no statistically significant differences in survival, postoperative
      complications, or adverse events after complete and partial resection in benign
      tumors other than myxomas. Cardiac transplant was associated significantly with
      higher mortality rate (P=0.006). Overall mortality was associated to malignancy
      (P=0.0008), and adverse events during follow-up (P=0.005). CONCLUSIONS: Surgery
      for primary cardiac tumors in children has good early and long-term outcomes,
      with low recurrence rate. Rhabdomyomas are the most frequent surgical histotypes.
      Malignant tumors negatively affect early and late survival. Heart transplant is
      indicated when conservative surgery is not feasible. Lack of recurrence after
      partial resection of benign cardiac tumors indicates that a less risky tumor
      debulking is effective for a subset of histotypes such as rhabdomyomas and
      fibromas.

PMID- 22626747
TI  - Anti-inflammatory homoisoflavonoids from the tuberous roots of Ophiopogon
      japonicus.
AB  - Two new homoisoflavonoids, named ophiopogonone E (1) and ophiopogonanone H (2),
      together with thirteen known ones (3-15) were isolated from the tuberous roots of
      Ophiopogon japonicus. Their structures were elucidated by spectroscopic and
      chemical analyses. Compounds 7 and 15 were isolated from the genus for the first
      time. In addition, compounds 2-15 were evaluated for their effects on the
      inhibition of NO production induced by lipopolysaccharide in the murine
      microglial cell line BV-2. Compounds 2, 4, 6, 7, 10, 11 showed potent inhibitory
      effects on NO production with IC(50) values of 20.1, 17.0, 7.8, 5.1, 19.2 and
      14.4 MUM respectively.

PMID- 22626746
TI  - Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent
      anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus.
AB  - BACKGROUND: A recent case-control study suggested a benefit of hydroxychloroquine
      (HCQ) in lowering the risk of cardiac manifestations of neonatal lupus (cardiac
      NL) in pregnancies of anti-SSA/Ro-positive patients with systemic lupus
      erythematosus. A historical cohort assembled from 3 international databases was
      used to evaluate whether HCQ reduces the nearly 10-fold increase in risk of
      recurrence of cardiac-NL independently of maternal health status. METHODS AND
      RESULTS: Two hundred fifty-seven pregnancies of anti-SSA/Ro-positive mothers (40
      exposed and 217 unexposed to HCQ) subsequent to the birth of a child with cardiac
      NL were identified from 3 databases (United States, England, and France).
      Exposure was defined as the sustained use of HCQ throughout pregnancy with
      initiation before 10 weeks of gestation. The recurrence rate of cardiac-NL in
      fetuses exposed to HCQ was 7.5% (3 of 40) compared with 21.2% (46 of 217) in the
      unexposed group (P=0.050). Although there were no deaths in the exposed group,
      the overall case fatality rate of the cardiac-NL fetuses in the unexposed group
      was 21.7%. In a multivariable analysis that adjusted for database source,
      maternal race/ethnicity, and anti-SSB/La status, HCQ use remained significantly
      associated with a decreased risk of cardiac-NL (odds ratio, 0.23; 95% confidence
      interval, 0.06-0.92; P=0.037). Similar results were obtained with propensity
      score analysis, an alternative approach to adjust for possible confounding by
      indication. CONCLUSION: Aggregate data from a multinational effort show that in
      mothers at high risk of having a child with cardiac-NL, the use of HCQ may
      protect against recurrence of disease in a subsequent pregnancy.

PMID- 22626748
TI  - Antispasmodic effect of 4'-methylepigallocatechin on guinea pig ileum.
AB  - The antispasmodic effect of 4'-methylepigallocatechin (MEC), which was isolated
      from Maytenus rigida Mart (Celestraceae), was investigated in vitro in guinea pig
      intestinal segments. In the isolated ileum, MEC (1 nM-100 MUM) did not modify the
      ileal spontaneous tonus or the electrically elicited contractions. MEC (8 MUM)
      significantly (p<0.01) reduced the submaximal contractions induced by histamine
      (2 MUM), carbachol (100 MUM) and BaCl2 (0.03 M). An additive relaxing action
      (p<0.001) was observed by co-incubation of verapamil (10 nM) and MEC (8 MUM).
      Although MEC (1 nM-100 MUM) did not modify the contractions elicited by 60 mM
      KCl, it significantly reduced the CaCl2 contractile response without changing the
      EC50 (effective concentration of CaCl2 causing 50% of maximum response). In
      brief, these results show that MEC has a potent ileal spasmolytic effect and
      blocks spasms induced by specific and nonspecific stimuli. Importantly, the
      spasmolytic effects were attained at low concentrations and might be related to
      the symptomatic relief of abdominal pain that is obtained from the use of the M.
      rigida stem bark.

PMID- 22626749
TI  - Gelam honey inhibits lipopolysaccharide-induced endotoxemia in rats through the
      induction of heme oxygenase-1 and the inhibition of cytokines, nitric oxide, and
      high-mobility group protein B1.
AB  - Malaysian Gelam honey has anti-inflammatory and antibacterial properties, a high
      antioxidant capacity, and free radical-scavenging activity. Lipopolysaccharide
      (LPS) stimulates immune cells to sequentially release early pro- and anti
      inflammatory cytokines and induces the synthesis of several related enzymes. The
      aim of this study was to investigate the effect of the intravenous injection of
      honey in rats with LPS-induced endotoxemia. The results showed that after 4h of
      treatment, honey reduced cytokine (tumor necrosis factor-alpha, interleukins
      1beta, and 10) and NO levels and increased heme oxygenase-1 levels. After 24h, a
      decrease in cytokines and NO and an increase in HO-1 were seen in all groups,
      whereas a reduction in HMGB1 occurred only in the honey-treated groups. These
      results support the further examination of honey as a natural compound for the
      treatment of a wide range of inflammatory diseases.

PMID- 22626750
TI  - Midterm results of the modified Ross/Konno procedure in neonates and infants.
AB  - BACKGROUND: The management of congenital aortic stenosis in neonates and infants
      continues to be a surgical challenge. We have performed the modified Ross-Konno
      procedure for patients who have severe aortic insufficiency or significant
      residual stenosis after balloon aortic dilation. The midterm results of this
      procedure were evaluated in this subset of patients. METHODS: Between 1994 and
      2010, a total of 24 patients younger than 1 year of age underwent the modified
      Ross-Konno procedure. The diagnoses were aortic stenosis with or without
      subaortic stenosis (n = 16), Shone's complex (n = 7), and interrupted aortic arch
      with subaortic stenosis (n = 1). The aortic root was replaced with a pulmonary
      autograft, and the left ventricular outflow tract (LVOT) was enlarged with a
      right ventricular infundibular free wall muscular extension harvested with the
      autograft. RESULTS: Age at operation ranged from 1 to 236 days (median 28 days).
      The median follow-up period was 81 months (range 1-173 months). There was 1 early
      death and no late mortality. Overall the 1-, 2-, and 5-year survival rate was 95%
      +/- 4.5%. Freedom from aortic stenosis was 94.7% +/- 5.1% at 1, 2, and 5 years.
      Less than mild aortic insufficiency was 93.3% +/- 6.4% at 2 years, and 74.7% +/-
      12.9% at 5 years. In total, 23 reoperations and reinterventions were performed;
      14 were allograft conduit replacements. Two patients required aortic valve
      plasty. None required valve replacement. The reintervention-free rate was 64.6%
      +/- 10.8% at 2 years and 36.9% +/- 11.3% at 5 years. CONCLUSIONS: Pulmonary
      autografts demonstrated good durability with low mortality and morbidity. This
      study shows that the modified Ross-Konno procedure can be a practical choice in
      selective cases for complex LVOT stenosis in neonates and infants.

PMID- 22626751
TI  - Impact of blood product transfusion on short and long-term survival after cardiac
      surgery: more evidence.
AB  - BACKGROUND: Despite the proven benefits in hemorrhagic shock, blood transfusions
      have been linked to increased morbidity and mortality. The short-term adverse
      effects of blood transfusion in cardiac surgical patients are well documented but
      there are very few studies that adequately assess the long-term survival. This
      study was undertaken to evaluate the effects of transfusion on both short-term
      and long-term survival after cardiac surgery. METHODS: Data from 5,342 patients
      who underwent a cardiac surgical procedure from January 2002 to December 2005 at
      our institution were reviewed. The effect of transfusion of packed red blood
      cells (PRBC) and other blood products was tested in a 2-level approach of
      transfusion (any) versus no transfusion, and also a 4-level approach of
      transfusion (PRBC, other blood products, and both blood and blood products)
      versus no transfusion. Long-term survival data of these patients were obtained.
      Cox proportional hazard models, Kaplan-Meier survival plots, and hazard functions
      were used to compare the groups. RESULTS: A total of 3,013 of the 5,342 study
      patients (56.4%) received transfusion during or within 72 hours of their cardiac
      surgery. Median time to death was significantly lower for patients who received
      transfusions; 1.15 years for PRC and 0.83 years for any transfusion, compared
      with 4.68 years in the non-transfused group. The overall 30-day mortality was
      1.7%, but in patients who received transfusions (3.6%) was significantly higher
      than the non-transfused group (0.3%, p<0.001). The 1-year mortality (overall
      3.9%) in the transfused group (7.3%, p<0.001) was also significantly higher than
      that in the non-transfused group (1.3%). The 5-year mortality rate in the
      transfused group was more than double that in the non-transfused group (16% vs
      7%). After correction for comorbidities and other factors, transfusion was still
      associated with a 66% increase in mortality. CONCLUSIONS: This study suggests
      that blood or blood product transfusion during or after cardiac surgery is
      associated with increased short-term and long-term mortality. It reinforces the
      need for prospective randomized controlled studies for evaluation of restrictive
      transfusion triggers and objective clinical indicators for transfusion in the
      cardiac surgical patient population.

PMID- 22626752
TI  - Pulmonary endarterectomy: recent changes in a single institution's experience of
      more than 2,700 patients.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a known
      sequela of acute pulmonary embolic disease and yet remains underdiagnosed.
      Although nonsurgical options for patients with CTEPH have become increasingly
      available, including pulmonary artery hypertensive medical therapy, surgical
      endarterectomy provides the most appropriate intervention as a potential cure for
      this debilitating disorder. This article summarizes the most recent outcomes of
      pulmonary endarterectomy at a single institution over the past 12 years, with
      emphasis on the surgical approach to segmental-level chronic thromboembolic
      disease. METHODS: More than 2,700 pulmonary endarterectomy operations have been
      performed at the University of California, San Diego Medical Center. Because of
      recent changes in the patient population and in surgical results, 1,500 patients
      with symptomatic chronic thromboembolic disease who underwent pulmonary
      endarterectomy between March 1999 and December 2010 were analyzed. The outcomes
      for the more recent 500 patients, compared with the previous 1,000 were studied.
      RESULTS: In-hospital mortality for the cohort of 1,000 patients (group 1) was
      5.2% compared with 2.2% for the last 500 operations (group 2) (p < 0.01). There
      was no mortality in the last 260 consecutive patients undergoing isolated
      pulmonary endarterectomy. More patients presented with segmental type III disease
      in the more recent 500 patients (21.4% versus 13.1%; p < 0.001). Between the 2
      patient groups, there was a comparable decline in pulmonary vascular resistance
      (PVR) (group 1: 861.2 +/- 446.2 to 94.8 +/- 204.2 dynes/sec/cm(-5); group 2:
      719.0 +/- 383.2 to 253.4 +/- 148.6 dynes/sec/cm(-5)) and mean pulmonary artery
      (PA) pressures (group 1: 46.1 +/- 11.4 to 28.7 +/- 10.1 mm Hg; group 2: 45.5 +/-
      11.6 to 26.0 +/- 8.4 mm Hg) after endarterectomy. CONCLUSIONS: Despite a patient
      population with more distal disease, results continue to improve. Pulmonary
      endarterectomy for patients with CTEPH results in significant pulmonary
      hemodynamic improvement, with favorable outcomes achievable even in patients with
      distal segmental-level chronic thromboembolic disease.

PMID- 22626753
TI  - Surgical experience with cardiac papillary fibroelastoma over a 15-year period.
AB  - BACKGROUND: Papillary fibroelastomas are rare, benign cardiac tumors. They are
      predominantly asymptomatic. However, they can lead to serious complications,
      namely thromboembolic events. Symptomatic lesions can be managed primarily with
      surgical excision and valvular preservation. Controversy exists as to the
      management of asymptomatic lesions. METHODS: All patients diagnosed with cardiac
      papillary fibroelastoma between 1996 and 2012 at a single institution were
      queried for clinical and pathologic characteristics. RESULTS: Twenty-three
      patients with 29 lesions were identified. Most lesions were solitary, less than
      1.0 cm in diameter, and occurred in patients greater than 60 years of age. The
      most common presentation was thromboembolic complication. All were managed
      successfully with surgical excision. One patient developed a recurrence or
      metachronous lesion within 3 months of initial surgical intervention.
      CONCLUSIONS: Papillary fibroelastomas are rare, benign, predominantly
      asymptomatic cardiac tumors that can cause potentially serious complications. The
      natural history and etiology of papillary fibroelastomas are largely unknown.
      Controversy exists over the management of asymptomatic lesions. However, there is
      consensus that symptomatic lesions should undergo surgical excision with valvular
      preservation when possible. A unique case of a possible papillary fibroelastoma
      recurrence is also described.

PMID- 22626754
TI  - Transcatheter closure of congenital perimembranous ventricular septal defect in
      children using symmetric occluders: an 8-year multiinstitutional experience.
AB  - BACKGROUND: Perimembranous ventricular septal defects (pmVSDs) are one of the
      most common forms of congenital cardiac malformation in children. Results of
      transcatheter pmVSD closure remain debatable, prompting the need for further
      evaluation with regard to the safety and efficacy of this procedure. The aim of
      the study was to analyze the safety, efficacy, and long-term follow-up data
      associated with transcatheter closure of pmVSDs in children using symmetric
      occluders. METHODS: From December 2002 to October 2011, 525 children with pmVSDs
      between 2 and 12 years of age underwent transcatheter closure at three major
      heart centers in northwest China with symmetric pmVSD occluders. All patients
      were followed up until October 2011 with electrocardiogram and transthoracic
      echocardiography. Adverse events were recorded and evaluated. RESULTS: There were
      252 male and 273 female patients with an average weight of 21.5 kg. The mean age
      at the time of transcatheter closure was 5.6 years, and the average ratio of
      pulmonic to systemic blood flow was 2.5. Transcatheter intervention was
      successfully performed in 502 patients (95.6%). The median device size implanted
      was 6.5 mm (range, 4 to 18 mm). During a median 45-month follow-up period, no
      mortality occurred. A total of three major adverse events (0.6%) were reported;
      two were valve-related. Meanwhile, 104 minor adverse events were detected during
      the entire follow-up period. All individuals experiencing major adverse events
      were younger than 3 years of age. The incidence of major adverse events in
      patients younger than 3 years old was significantly higher than that of patients
      older than 3 years old (3.75% versus 0.00%; Fisher's exact test p=0.004).
      CONCLUSIONS: Data from the current study suggest that transcatheter pmVSD closure
      using symmetric occluders displayed an excellent success rate and long-term
      follow-up results. The transcatheter approach provides a less-invasive
      alternative to open surgery and displays some promise in the treatment of pmVSDs
      in certain patient populations.

PMID- 22626755
TI  - Long-term results of mitral valve repair for severe mitral regurgitation in
      infants: fate of artificial chordae.
AB  - BACKGROUND: The experience with mitral valve repair for severe mitral
      regurgitation in infants was retrospectively reviewed. METHODS: From 1978 to
      2009, 15 infant patients (4 boys, 7.2+/-3.2 months old) underwent mitral valve
      repair for severe mitral regurgitation. The etiology of mitral regurgitation
      according to Carpentier classification was type I in 1 patient, type II in 10
      patients, and type III in 4 patients. Artificial chordal replacement was
      performed in 11 patients. The follow-up course was completed in all patients,
      with a median follow-up period of 10.2 years (range, 2.2 to 33.4 years). RESULTS:
      There were no operative or in-hospital mortalities. The actuarial survival and
      freedom from reoperation rates at 10 years were 89% and 65%, respectively. Five
      patients required redo mitral valve surgery, including 4 patients needing mitral
      valve replacement. Three of 4 patients with type III mitral regurgitation, caused
      by congenital subvalvar structural abnormality, required redo mitral valve
      surgery. In 11 patients who underwent artificial chordal reconstruction, 2 (18%)
      required mitral valve replacement during the early postoperative period, whereas
      the remaining patients showed no recurrent mitral regurgitation during the entire
      study period. The latest echocardiography findings at 7.3 years after the
      operation showed that the left ventricular diastolic diameter, mitral valve
      diameter, and ejection fraction were 99.2%+/-5.0% of normal, 101.7%+/-13.3% of
      normal, and 0.741+/-0.058, respectively. CONCLUSIONS: Long-term durability of
      mitral valve repair for severe mitral regurgitation in infants was satisfactory.
      Artificial chordal reconstruction is an effective procedure without an elevated
      risk of late reoperation.

PMID- 22626756
TI  - The valve-in-valve operation for aortic homograft dysfunction: a better option.
AB  - BACKGROUND: Reoperations on dysfunctional aortic homografts often require root
      reconstruction with coronary reanastomosis. This is associated with substantial
      perioperative morbidity and mortality. Resecting compromised aortic homograft
      valve leaflets and seating a new valve within the homograft annulus avoids root
      reconstruction and is a viable alternative. METHODS: We retrospectively evaluated
      50 patients undergoing reoperations on dysfunctional homografts between 1999 and
      2011. Outcomes were compared between valve-in-valve (ViV) and aortic valve
      prosthetic conduit (AVR-C) procedures. RESULTS: Twenty-eight patients underwent
      ViV, and 22 had AVR-C. Groups were similar in age, sex, and incidence of
      endocarditis and renal failure. Median time between homograft and index procedure
      was 8.5 years for AVR-C and 8 years for ViV patients (p=0.93). Patients
      undergoing AVR-C had longer cardiopulmonary bypass (282 versus 151 minutes;
      p<0.001) and cross-clamp (207 versus 106 minutes; p<0.001) times and received
      significantly more intraoperative red blood cell transfusions than ViV patients
      (36.4% versus 7.1%; p=0.014). Patients undergoing ViV had shorter intensive care
      unit stays (47 hours versus 67 hours for AVR-C; p=0.049) and fewer postoperative
      red blood cell transfusions (21.4% versus 54.5%; p=0.020). There were trends
      toward shorter ventilation times for ViV patients (6 hours versus 11 hours for
      AVR-C; p=0.077), shorter postoperative length of stay (7 days versus 9 days;
      p=0.092), and fewer readmissions (3.6% versus 19.0%; p 0.073). One operative
      mortality occurred in the AVR-C group. CONCLUSIONS: The strategy of replacing
      aortic valve leaflets in a failed calcified homograft, with a valve seated inside
      the annulus, is a safe alternative to root reconstruction. Preserving root
      architecture and coronary buttons facilitates shorter cardiopulmonary bypass and
      cross-clamp times, and directly impacts transfusions, intensive care unit time,
      hospital stay, and readmission rates.

PMID- 22626757
TI  - Improving left ventricular outflow tract obstruction repair in common
      atrioventricular canal defects.
AB  - BACKGROUND: Left ventricular outflow tract obstruction (LVOTO) is the second most
      frequent reason for reoperation after atrioventricular canal (AVC) defect repair.
      Limited data are available on the mechanisms of LVOTO, their treatment, and
      outcomes. METHODS: Between 1998 and 2010, 56 consecutive children with AVC
      underwent 68 LVOTO procedures. The AVC was partial in 4, transitional in 9, and
      complete in 43. The LVOTO procedure was required in 21 patients at the primary
      AVC repair, and the initial LVOTO procedure in 35 patients was a late reoperation
      after AVC repair. RESULTS: During a mean follow-up of 50+/-41 months, 5 patients
      (24%) with LVOTO repair at AVC repair required a reoperation for LVOTO, and 7
      patients (20%) whose initial LVOTO repair was a reoperation required a second
      reoperation for LVOTO repair. Overall freedom from LVOTO reoperation was 98.5% at
      1 year, 92.5% at 3 years, 81% at 5 years, 72.2% at 7 years, and 52.5% at 10 and
      12 years. The freedom from reoperation was neither significantly different
      between partial, transitional, and complete AVC (p=0.78) nor between timing of
      the LVOT procedure (p=0.49). Modified single-patch AVC repair was associated with
      a higher LVOTO reoperation rate (p=0.04). Neither the mechanisms leading to LVOTO
      nor the surgical techniques used were independent predictors of reoperation.
      CONCLUSIONS: LVOTO in AVC is a complex and multifactorial disease. Aggressive
      surgical repair has improved late outcomes; however, risk factors for reoperation
      and the ideal approach for repair remain to be defined.

PMID- 22626758
TI  - Should orthotopic heart transplantation using marginal donors be limited to
      higher volume centers?
AB  - BACKGROUND: This study examined whether institutional volume impacts outcomes
      after orthotopic heart transplantation (OHT) utilizing marginal donors. METHODS:
      Adult patients undergoing OHT with the use of marginal donors between 2000 and
      2010 were identified in the United Network for Organ Sharing database. A
      previously derived and validated donor risk score (range, 1 to 15) was used to
      define marginal donors as those in the 90th percentile of risk (score>=7).
      Patients were stratified into equal-size tertiles based on overall institutional
      OHT volume. Posttransplant outcomes were compared between these center cohorts.
      RESULTS: A total of 3,176 OHTs utilizing marginal donors were identified. In Cox
      regression analysis, recipients undergoing OHT at low-volume centers were at
      significantly increased risk of 30-day (hazard ratio 1.82 [1.31 to 2.54],
      p<0.001), 1-year (hazard ratio 1.40 [1.14 to 1.73], p=0.002), and 5-year
      posttransplant mortality (hazard ratio 1.29 [1.10 to 1.52], p=0.02). These
      findings persisted after adjusting for recipient risk, differences in donor risk
      score, and year of transplantation (each p<0.05). In Kaplan-Meier analysis, there
      was a similar trend of decreasing 1-year survival with decreasing center volume:
      high (86.0%), intermediate (85.7%), and low (81.2%; log rank p=0.003). Drug
      treated rejection within the first post-OHT year was more common in low-volume
      versus high-volume centers (34.3% versus 24.2%, p<0.001). At an overall mean
      follow-up of 3.4+/-2.9 years, low-volume centers also had higher incidences of
      death due to malignancy (2.8% versus 1.3%, p=0.01) or infection (6.2% versus
      4.1%, p=0.02). CONCLUSIONS: Consolidating the use of marginal donors to higher
      volume centers may be prudent in improving post-OHT outcomes in this higher risk
      patient subset.

PMID- 22626759
TI  - Open repair of chronic aortic dissections using deep hypothermia and circulatory
      arrest.
AB  - BACKGROUND: There has been great enthusiasm for thoracic endograft repair of
      chronic thoracic or thoracoabdominal aortic dissection (ChAD) given the low
      operative morbidity and mortality. However long-term results are unknown and
      early reintervention is common. This study examines the early and late results of
      open repair of ChAD using deep hypothermia and circulatory arrest (DHCA).
      METHODS: From January 1995 to December 2009, 343 patients had open repair of
      descending thoracic or thoracoabdominal aneurysms using DHCA. Of these
      individuals, 93 patients had open repair of ChAD with DHCA. All patients
      undergoing elective procedures underwent preoperative cardiac catheterization.
      Lumbar drains were not placed preoperatively. Visceral or renal artery bypass was
      performed in 20% of patients. Supraaortic branches were bypassed in 14% of
      patients. RESULTS: Mean age was 60 +/- 14 years. Men composed 77% of the cohort.
      Aortic replacement encompassed the descending aorta in 29% of patients, type I
      thoracoabdominal repair was performed in 25% of patients, type II
      thoracoabdominal repair was performed in 40% of patients, and arch replacement
      was performed in 24% of patients. Operative mortality was 2.2%, renal failure
      requiring dialysis was 0%, paralysis occurred in 1.1% of patients, stroke
      occurred in 1.1% of patients, prolonged intubation was needed in 9.7% of
      patients, and tracheostomy was needed in 2.2% of patients. Postoperative length
      of stay was 10.5 +/- 7.6 days. One-, 3-, 5-, and 10-year survival rates were 93%,
      90%, 79%, and 61%, respectively. Reintervention was necessary in 2.2% of patients
      for graft infection, in 2.2% of patients for anastomotic pseudoaneurysm, and in
      4.4% of patients for growth of a distal aortic aneurysm. CONCLUSIONS: Open repair
      of ChAD with DHCA has low operative morbidity and mortality. Long-term survival
      is very good with low rates of reintervention. Endovascular repair of ChAD does
      not have proven short- or long-term efficacy.

PMID- 22626760
TI  - A systematic review of pulmonary embolism in patients with lung cancer.
AB  - Pulmonary embolism (PE) is increasingly recognized as causing significant
      morbidity and mortality in modern societies; however, little is known about PE in
      patients with lung cancer. We systematically reviewed Medline, Web of Science,
      and the Cochrane Library databases and selected 26 studies, including 2
      randomized controlled trials, and 4 prospective, 18 retrospective cohort, and 2
      case-control studies. Overall incidence of PE was 3.6%. Pulmonary embolism
      abbreviated survival in 2 studies when the diagnosis was synchronous with lung
      cancer. Venous thromboembolism prophylaxis, treatment, and surveillance are
      inconsistently reported. Clinical outcome data pertaining to this topic are
      limited and of overall poor methodologic quality.

PMID- 22626761
TI  - Surgical repair of ventricular septal defect after myocardial infarction:
      outcomes from the Society of Thoracic Surgeons National Database.
AB  - BACKGROUND: The development of a ventricular septal defect (VSD) after myocardial
      infarction (MI) is an uncommon but highly lethal complication. We examined The
      Society of Thoracic Surgeons database to characterize patients undergoing
      surgical repair of post-MI VSD and to identify risk factors for poor outcomes.
      METHODS: This was a retrospective review of The Society of Thoracic Surgeons
      database to identify adults (aged>=18 years) who underwent post-MI VSD repair
      between 1999 and 2010. Patients with congenital heart disease were excluded. The
      primary outcome was operative death. The covariates in the current The Society of
      Thoracic Surgeons model for predicted coronary artery bypass grafting operative
      death were incorporated in a logistic regression model in this cohort. RESULTS:
      The study included 2,876 patients (1,624 men [56.5%]), who were a mean age of
      68+/-11 years. Of these, 215 (7.5%) had prior coronary artery bypass grafting
      operations, 950 (33%) had prior percutaneous intervention, and 1,869 (65.0%) were
      supported preoperatively with an intraaortic balloon pump. Surgical status was
      urgent in 1,007 (35.0%) and emergencies in 1,430 (49.7%). Concomitant coronary
      artery bypass grafting was performed in 1,837 (63.9%). Operative mortality was
      54.1% (1,077 of 1,990) if repair was within 7 days from MI and 18.4% (158 of 856)
      if more than 7 days from MI. Multivariable analysis identified several factors
      associated with increased odds of operative death. CONCLUSIONS: In the largest
      study to date to examine post-MI VSD repair, ventricular septal rupture remains a
      devastating complication. As alternative therapies emerge to treat this
      condition, these results will serve as a benchmark for future comparisons.

PMID- 22626762
TI  - Are thromboembolic and bleeding complications a drawback for composite aortic
      root replacement?
AB  - BACKGROUND: Valve-preserving aortic root reconstruction is being performed with
      increasing frequency. Independent of durability concerns, enthusiasm for
      retaining the native valve is often championed on the presumption that composite
      graft replacement of the aorta will be complicated by thromboembolism and
      bleeding. Our goal in this late follow-up study is to determine if
      thromboembolism or bleeding, or both, are indeed problematic after composite
      aortic root replacement. METHODS: Between 1995 and 2011, 306 patients (mean age,
      56+/-14 years) underwent composite graft replacement of the aorta. St. Jude
      mechanical valve conduits (St. Jude Medical, St Paul, MN) were used in 242
      patients, and 64 received a biologic conduit. Long-term postoperative follow-up
      (mean, 56 months; range, 1 to 97 months) was performed through our Aortic
      Database, supplemented by patient interviews and use of the Social Security Death
      Index. RESULTS: Hospital mortality was 2.9% overall and 1.4% in the last 8 years.
      Kaplan-Meier curves showed freedom (+/-standard deviation) from bleeding, stroke,
      and distal embolism as 94.3%+/-1.7% at 5 years and 91.3%+/-2.4% at 10 years.
      Survival was 93.5%+/-1.8% at 5 years and 80.9%+/-4.6% at 10 years, which was not
      statistically different from that for an age- and sex-matched population in
      Connecticut. Freedom from reoperation of the aortic root was 99% at 10 years.
      CONCLUSIONS: Patients had excellent survival and few thromboembolic and bleeding
      complications after composite aortic root replacement. These data supporting
      minimal morbidity in the setting of well-established durability should be used to
      put alternative procedures, such as valve-preserving aortic root reconstruction,
      into context.

PMID- 22626764
TI  - The metabolic syndrome and coronary artery disease: a structural equation
      modeling approach suggestive of a common underlying pathophysiology.
AB  - OBJECTIVE: The purpose of this research was to utilize a structural equation
      modeling (SEM) approach to simultaneously examine the relationship among the
      Metabolic Syndrome (MetSyn) and coronary artery calcification (CAC), a surrogate
      marker for sub-clinical atherosclerosis and coronary artery disease (CAD).
      MATERIALS/METHODS: Data were derived from the Spokane Heart Study (SHS), a
      prospective study designed to examine the role of traditional and non-traditional
      biological, psychological, and behavioral risk factors predictive of CAC. Study
      participants included 434 non-clinical healthy volunteers (54% female, 46% male;
      mean age of 56 years) who were asymptomatic for CAD at enrollment and had
      complete data for the primary variables of interest (MetSyn components and CAC)
      during the data collection period (i.e., 2002-2006). A confirmatory factor
      analysis (CFA) was conducted on the MetSyn factor with the following indicator
      variables: body mass index, fasting glucose, high-density lipoprotein
      cholesterol, fasting triglyceride levels, and systolic blood pressure. SEM was
      used to test the theoretical model that the MetSyn is associated with CAC.
      RESULTS: This study demonstrated that body mass index, fasting glucose, fasting
      triglyceride levels, HDL cholesterol, and blood pressure do cluster together
      under a single latent factor, and that this latent factor is associated with CAC.
      CONCLUSIONS: Our results highlight the possibility that there is a common
      pathophysiological pathway that could explain the relationship between the MetSyn
      and CAD. Future studies should examine these relationships in a prospective
      fashion for early detection and prevention of CAD and to identify ideal time
      points for clinical intervention.

PMID- 22626763
TI  - Acetylation and deacetylation--novel factors in muscle wasting.
AB  - We review recent evidence that acetylation and deacetylation of cellular
      proteins, including transcription factors and nuclear cofactors, may be involved
      in the regulation of muscle mass. The level of protein acetylation is balanced by
      histone acetyltransferases (HATs) and histone deacetylases (HDACs) and studies
      suggest that this balance is perturbed in muscle wasting. Hyperacetylation of
      transcription factors and nuclear cofactors regulating gene transcription in
      muscle wasting may influence muscle mass. In addition, hyperacetylation may
      render proteins susceptible to degradation by different mechanisms, including
      intrinsic ubiquitin ligase activity exerted by HATs and by dissociation of
      proteins from cellular chaperones. In recent studies, inhibition of p300/HAT
      expression and activity and stimulation of SIRT1-dependent HDAC activity reduced
      glucocorticoid-induced catabolic response in skeletal muscle, providing further
      evidence that hyperacetylation plays a role in muscle wasting. It should be
      noted, however, that although several studies advocate a role of hyperacetylation
      in muscle wasting, apparently contradictory results have also been reported. For
      example, muscle atrophy caused by denervation or immobilization may be associated
      with reduced, rather than increased, protein acetylation. In addition, whereas
      hyperacetylation results in increased degradation of certain proteins, other
      proteins may be stabilized by increased acetylation. Thus, the role of
      acetylation and deacetylation in the regulation of muscle mass may be both
      condition- and protein-specific. The influence of HATs and HDACs on the
      regulation of muscle mass, as well as methods to modulate protein acetylation, is
      an important area for continued research aimed at preventing and treating muscle
      wasting.

PMID- 22626765
TI  - The craniocervical flexion test: an investigation of performance in young
      asymptomatic subjects.
AB  - INTRODUCTION: The Deep Cervical Flexors (DCFs) provide support and segmental
      stability to the cervical spine. However, their endurance capacity can be reduced
      in cervicogenic disorders. The Craniocervical Flexion Test (CCFT) is regarded as
      the most effective means of assessing the contractile performance of these
      muscles. However, limited normative data exists to serve as a reference point
      during diagnosis. AIM: This study examined CCFT performance in a group of young
      asymptomatic subjects and investigated the influence of physical activity levels,
      age and gender on CCFT score. METHOD: The most recent CCFT protocol as described
      by Jull et al. (2008) was used. Baseline assessment scores along with certain
      patient characteristics were recorded on one occasion. RESULTS: For testing, 34
      asymptomatic subjects were recruited (24 females, 10 males with a mean age of
      21.5 +/- 2.15 years). The median baseline assessment score was 24 mmHg
      (interquartile range = 3). Physical activity levels, age or gender did not
      significantly correlate with DNF endurance (P > 0.05). CONCLUSION: The Median
      Baseline Assessment score was 24 mmHg (interquartile range = 3). Between-subject
      variability was high while physical activity levels; age or gender did not appear
      to influence the DCF muscle tonic holding capacity. The small heterogeneous
      sample involved in this study highlights the need for high quality normative
      studies to validate these findings.

PMID- 22626766
TI  - The expression of interleukin-8 and interleukin-8 receptors in endometrial
      carcinoma.
AB  - Interleukin-8 (IL-8) is a pro-inflammatory cytokine which exerts its effects via
      binding to 2 receptors, CXCR1 and CXCR2 and is known to promote angiogenesis,
      mitogenesis and motogenesis in cancer. IL-8 is over expressed in endometrial
      carcinoma, but the expression of CXCR1 and CXCR2 in endometrial carcinoma has not
      been previously investigated. The aim of this study was to determine the
      expression of IL-8 receptors in endometrial carcinoma. The expression of CXCR1
      and CXCR2 was studied in endometrial carcinomas and normal endometrium by
      immunohistochemistry in 101 tumours. IL-8 and IL-8 receptor expression was also
      studied by Real-time quantitative PCR (RT-qPCR) in 17 tumours in comparison to
      normal endometrium. The expression profile was correlated to the clinico
      pathological features of the tumours. Immunohistochemistry showed CXCR1 and CXCR2
      were expressed in all cases of endometrial carcinoma, with CXCR1 showing stronger
      expression. There was a statistically significant correlation between CXCR2
      staining intensity and tumour grade (P=0.012) and disease free survival (P=0.015)
      independently. On RT-qPCR, 14/17, 15/17 and 16/17 tumours showed significant
      increase in IL-8, CXCR1 and CXCR2 expression levels in comparison to normal
      endometrium, with median fold increase of 42-fold, 51-fold and 27-fold,
      respectively. This is the first report of the expression of IL-8 receptors in
      endometrial carcinoma and the results show an association between IL-8 and IL-8
      receptors and the pathogenesis of endometrial carcinoma, and represent potential
      prognostic biomarkers and therapeutic targets.

PMID- 22626767
TI  - Divergent effects of a CLA-enriched beef diet on metabolic health in ApoE-/- and
      ob/ob mice.
AB  - Conjugated linoleic acid (CLA) is found naturally in meat and dairy products, and
      represents a potential therapeutic functional nutrient. However, given the
      discrepancies in isomer composition and concentration, controversy surrounds its
      proposed antidiabetic, antiobesity effects. This study focused on the effects of
      CLA-enriched beef (composed predominantly of c9, t11-CLA) in two separate models
      of metabolic disease: proatherosclerotic ApoE(-/-) mice and diabetic, leptin
      deficient ob/ob mice. Animals were fed CLA-enriched beef for 28 days, and markers
      of the metabolic syndrome and atherosclerosis were assessed. Comprehensive
      hepatic transcriptomic analysis was completed to understand divergent metabolic
      effects of CLA. CLA-enriched beef significantly reduced plasma glucose, insulin,
      nonesterified fatty acid and triacylglycerol and increased adiponectin levels in
      ob/ob mice. In contrast, plasma lipid profiles and glucose homeostasis
      deteriorated and promoted atherosclerosis following the CLA-enriched beef diet in
      ApoE(-/-) mice. Hepatic transcriptomic profiling revealed divergent effects of
      CLA-enriched beef on insulin signaling and lipogenic pathways, which were
      adversely affected in ApoE(-/-) mice. This study demonstrated clear divergence in
      the effects of CLA. CLA-enriched beef improved metabolic flexibility in ob/ob
      mice, resulting in enhanced insulin sensitivity. However, CLA-enriched diet
      increased expression of lipogenic genes, resulting in inefficient fatty acid
      storage which increases lipotoxicity in peripheral organs, and led to profound
      metabolic dysfunction in ApoE(-/-) mice. While CLA may have potential health
      effects, in some circumstances, caution must be exercised in presenting this
      bioactive lipid as a potential functional food for the treatment of metabolic
      disease.

PMID- 22626768
TI  - Challenges of work-life balance for women physicians/mothers working in
      leadership positions.
AB  - BACKGROUND: Female leadership in medicine is still disproportionately small,
      which might be due to the barriers of combining work and family. OBJECTIVES: The
      aim of this study was, first, to perform a strengths, weakness, opportunities,
      and threats (SWOT) analysis and, second, to create a strategic concept for career
      development. METHODS: In this study, all women in leadership positions in the
      health care system in Vienna, Austria, with at least 1 child (n = 8), were
      interviewed about the advantages and disadvantages of gender with regard to
      career development, the strengths and weaknesses of female leadership, and their
      work-life balance. Different factors that influenced the work-life balance were
      specified, and career strategies to realize adequate solutions were developed.
      RESULTS: The sporadic focus on career advancement, time-consuming child care,
      responsibility for family life, and a woman's tendency toward understatement were
      barriers to career development. Work-family enrichment has a positive spillover
      effect that spreads positive energy and helps to balance the work-life
      relationship. For each individual, the allocation and interaction of different
      resources such as time, money, scope of decision making, and physical, emotional,
      and social resources, were essential to maintain the individual work-life
      balance. CONCLUSIONS: In addition to the existing "glass ceiling," the
      predominant responsibility for child care is still borne by the woman. However,
      mentoring programs, coaching, networking, and support of the partner or of other
      people help to strengthen female "soft" skills and achieve a work-life balance.

PMID- 22626769
TI  - Large animal models for the study of ovarian follicular dynamics in women.
AB  - Initial studies of the ovaries were based on postmortem anatomic descriptions,
      followed by histologic and endocrine approaches. The introduction of high
      resolution ultrasonography provided a long-awaited tool to image the reproductive
      tissues in situ in both animals and humans. Critical studies of the
      characteristics and control of ovarian follicular and luteal dynamics in nonhuman
      primates, rodents, and domestic farm animals have involved frequent (i.e., daily
      or multiple times a day) blood sampling and ultrasonography. Studies of this
      nature in women are difficult, and often unethical to conduct. Differences in
      antral folliculogenesis between humans and animals appear to be more in detail
      rather than in essence, and may reflect differences in intrinsic physiology or
      merely differences in our ability to detect changes in a given species. In women,
      the presence of endometrial shedding and symmetric luteal and follicular phases
      are different from that observed during the estrous cycles of domestic farm
      animals but despite these differences, general similarities in antral follicular
      dynamics exist. A continuous pattern of antral follicle development was
      originally proposed in domestic livestock species; however, the use of frequent
      serial ultrasonography and simultaneous endocrine profiling in these animal
      species has resulted in a broad understanding of follicular wave dynamics.
      Follicular waves have now been described in every species in which this approach
      has been used, including humans. The relatively large diameters of antral
      follicles in cows and mares, compared with monkeys, sheep, and rodents provide
      greater feasibility for characterizing antral follicular dynamics
      ultrasonographically. While the use of large animal models has increased our
      understanding of ovarian function and provides the hypothetical basis for studies
      in women, differences in vocabulary, culture, and research methodologies has
      hampered knowledge translation. These differences represent a systemic impediment
      to a broad understanding of ovarian function and limits progress and innovation
      in the development of safer and more efficacious treatments for infertility and
      contraception.

PMID- 22626770
TI  - Characterizing the behavior and reproductive biology of zoo-housed Sichuan takin
      (Budorcas taxicolor tibetana) using non-invasive techniques.
AB  - The Sichuan takin (takin; Budorcas taxicolor tibetana) is distributed in the
      Gansu and Sichuan providences of southern China and along eastern Tibet. Because
      of their ecology, few data on takin reproductive biology exist, with the
      exception of its mating season in the Sichuan province, which occurs from July
      through August. Therefore, the objectives were to: 1) characterize reproductive
      hormones in zoo-housed male and female takin, including pregnancy in the female,
      using non-invasive fecal steroid hormonal monitoring; 2) characterize behaviors
      of zoo-housed takin, emphasizing reproductive behaviors and activity budget; and
      3) assess the influence of season on births in North America and reproductive
      hormonal and behavioral activity. Fecal samples were collected 3 to 5 times per
      week from two adult males and three adult females. Extracted hormones were
      analyzed using an enzyme immunoassay for progestagen and androgen concentrations.
      Behavioral observations were collected for 2 yrs using an ethogram. In this
      study, season affected reproduction, specifically birth occurrences, reproductive
      cyclicity in females and androgen production in males. The duration of the
      estrous cycle was approximately 35 d and cycles occurred June through December.
      Androgen concentrations peaked in May through August. Season did not influence
      behavior; however, age and sex may affect some behaviors, including activity
      level, foraging and drinking, social affiliative behavior, and visibility from
      the visitor's viewpoint. In conclusion, fecal hormonal and behavioral analyses
      can provide information for management and conservation of this herd species.

PMID- 22626771
TI  - Compared to dinoprost tromethamine, cloprostenol sodium increased rates of estrus
      detection, conception and pregnancy in lactating dairy cows on a large commercial
      dairy.
AB  - Using two PGF(2alpha) treatments 14 days apart as a way to enhance estrus
      detection rate following the 2nd treatment is a reproductive management tool that
      continues to be used on large dairy farms. In one study, in cows with a
      functional CL and a dominant follicle, treatment with cloprostenol vs. dinoprost
      resulted in greater peripheral estradiol concentrations. The objective of the
      present study was to determine if cloprostenol could enhance pregnancy rates of
      cows in a large dairy herd using a PGF(2alpha) program for 1st artificial
      insemination (AI). Lactating dairy cows (n = 4549) were randomly assigned to
      receive two treatments of either 500 MUg cloprostenol or 25 mg dinoprost 14 days
      apart, with the 2nd treatment on the 1st day of the voluntary waiting period (57
      DIM). Cows detected in estrus within 5 days after the 2nd treatment were
      inseminated. There was no effect of treatment on day of estrus detection, with
      78% of cows inseminated on Days 3 or 4 following treatment. Cloprostenol
      increased (P < 0.01) estrus detection rates in 1st parity cows compared to
      dinoprost, 42.4 vs. 34.0%. In cows inseminated on Days 3 or 4 after treatment,
      cloprostenol increased (P = 0.05) conception rates compared to dinoprost, 38.3
      vs. 34.4%. When treatments and parities were combined, conception rates increased
      (P < 0.02) with interval after treatment (27.0, 36.4, and 44.5% for Days 1 or 2,
      Days 3 or 4, and Day 5, respectively). Cloprostenol increased (P = 0.02) overall
      pregnancy rate compared to dinoprost, 14.4 vs. 12.2%. In summary, cloprostenol
      increased fertility in 1st parity cows inseminated on Days 3 or 4 following
      treatment and subsequently enhanced pregnancy rates of 1st parity lactating dairy
      cows compared to dinoprost. Fertility appeared greater in cows expected to have
      had a young antral ovarian follicle at treatment.

PMID- 22626772
TI  - Blastocysts cloned from the Putian Black pig ear tissues frozen without
      cryoprotectant at -80 and -196 degrees Celsius for 3 yrs.
AB  - The Putian Black pig, as one of elite cultivars of endemic species in China, has
      been on the verge of extinction and urgently needs protection. Somatic cell
      nuclear transfer (SCNT) and noncryoprotected frozen tissue technology have
      successfully resurrected several mammalian species. Therefore, this study
      explored the primary feasibility of conserving this breed using a combination of
      both technologies. Skin tissues obtained from the ears of adult Putian Black
      boars were frozen without cryoprotectant at -20, -80, or -196  degrees C and
      stored for 3 yrs. Primary cell culture, passage and subculture were performed on
      frozen samples after being rapidly thawed at 39  degrees C and on fresh pig ear
      tissues (control). Cloned embryos were reconstructed using fibroblasts (from
      frozen and fresh tissues) with enucleated oocytes. Live cell lines were obtained
      from tissues frozen at -80 and at -196  degrees C and appeared to have normal
      proliferative activity after passage; furthermore, they directed cloned embryos
      to develop to the blastocyst stage after nuclear transfer. We concluded that the
      population of Putian Black pig might be increased in the future by transferring
      cloned blastocysts into synchronized recipient pigs.

PMID- 22626773
TI  - Control of the estrous cycle in guinea-pig (Cavia porcellus).
AB  - The aim of this work was to look for a simple method to obtain synchronized
      ovulation in guinea pigs under farming conditions while respecting animal
      welfare. The luteolytic activity of three different prostaglandins F2alpha
      (PGF2alpha) analogs (D-cloprostenol, D,L-cloprostenol and luprostiol) and a daily
      treatment with oral progestagen (altrenogest) was tested successively at
      different stages of the estrous cycle on the same group of females during a
      period of 8 mo. The estrous cycle length was not modified by the administration
      of PGF2alpha analogs, whatever the stage of the estrous cycle when the treatment
      was initiated. Our results led us to reject the use of PGF2alpha analog to induce
      practical synchronization of the estrus in this species. In females (n = 29),
      given 15 days with altrenogest (0.1 mL po once a day), ovulation occurred 4.43 +/
      0.13 days after the end of the treatment. Altrenogest treatment was followed by
      mating. No negative impacts of the treatment on the pregnancy rates, delivery
      rates and litter sizes were observed. This standard method of guinea-pig estrus
      synchronization is less stressful for the animals compared to techniques using
      progesterone tubing.

PMID- 22626774
TI  - Seasonal dynamics of sperm morphometric subpopulations and its association with
      sperm quality parameters in ram ejaculates.
AB  - Sperm morphologic assessment is considered an irreplaceable part of standard
      laboratory routine analyses in the diagnosis of male fertility. Thus, in an
      attempt to quantify the effects of season on sperm morphology and its functional
      significance in relation to sperm quality parameters, sperm head morphometric
      traits were analyzed by using an objective computerized analysis combined with
      principal components analysis (PCA) cluster analysis to establish the
      relationship between the distribution of the subpopulations found and sperm
      quality in each season. There were slight variations on sperm motility and sperm
      membrane integrity indexes (P > 0.05). However, the mean values for sperm
      concentration substantially changed among seasons in all individuals studied (P <
      0.01). There were significant differences in sperm morphometric parameters (P <
      0.01) as well as in the distribution of morphometric subpopulations between
      seasons (P < 0.001). In conclusion, this study confirmed that there was an
      important seasonal effect on sperm morphometric traits. In addition, the
      distribution of these subpopulations seems to be related to the season studied
      and the ejaculate quality which would be a very important indicator of sperm
      function. The substantial information derived from these morphometric
      subpopulations has provided new knowledge which can be used in future studies
      using sperm morphometry as a seasonal indicator in ram ejaculates.

PMID- 22626775
TI  - Effect of sericin on preimplantation development of bovine embryos cultured
      individually.
AB  - The silk protein sericin has been identified as a potent antioxidant in mammalian
      cells. This study was conducted to examine the effects of sericin on
      preimplantation development and quality of bovine embryos cultured individually.
      When two-cell-stage embryos were cultured individually for 7 days in CR1aa medium
      supplemented with 0, 0.1, 0.5, or 1% sericin, rates of total blastocyst formation
      and development to expanded blastocysts from embryos cultured with 0.5% sericin
      were higher (P < 0.05) than those from embryos cultured with 0 or 1% sericin.
      When embryos were cultured individually for 7 days in the CR1aa medium
      supplemented with 0 or 0.5% sericin under two oxidative stress conditions (50 or
      100 MUm H(2)O(2)), the addition of sericin significantly improved the blastocyst
      formation rate of embryos exposed to 100 MUm H(2)O(2). However, the protective
      effect of sericin was not observed in development of embryos exposed to 50 MUm
      H(2)O(2). When embryos were exposed to 100 MUm H(2)O(2) during culture, the DNA
      fragmentation index of total blastocysts from embryos cultured with 0.5% sericin
      was lower than blastocysts derived from embryos cultured without sericin (4.4 vs.
      6.8%; P < 0.01). In conclusion, the addition of 0.5% sericin to in vitro culture
      medium improved preimplantation development and quality of bovine embryos
      cultured individually by preventing oxidative stress.

PMID- 22626776
TI  - Estimation of genetic parameters for semen quality traits and growth rate in a
      paternal rabbit line.
AB  - Variance components of sperm quality traits were estimated in a paternal line of
      rabbits selected on the basis of daily weight gain (DG, g/day) between 28 and 63
      days of age. Features of the marginal posterior distributions for the genetic
      variance ratios, variance due to non-additive plus environmental permanent male
      effects, and variance due to litter of birth effects with respect to phenotypic
      variance are reported. The correlation between sperm quality traits and the
      selection criteria were also estimated. Nine sets of two-trait analyses were
      performed involving 12 908 DG records, 2231 ejaculates corresponding to 412
      males, and 14 700 animals in the pedigree file. Heritability values (h(2)) of
      sperm quality traits commonly evaluated in a classic spermiogram were 0.18, 0.19,
      and 0.12 for normal acrosome status (NAR) (%, percentage of sperm with intact
      acrosome), sperm abnormalities (ANR) (%, percentage of sperm abnormalities), and
      sperm motility (MOT) (%, percentage of total motile sperm cells), respectively.
      The h(2) of some motion computer-assisted sperm analysis (CASA) Parameters 0.09,
      0.11, 0.10, 0.11, 0.11 and 0.11 for average path velocity (VAP) (MUm/sec; average
      path velocity), straight-line velocity (VSL) (MUm/sec; straight-line velocity),
      curvilinear velocity (VCL) (MUm/sec; curvilinear velocity), linearity index (LIN)
      (%, linearity index), amplitude of lateral head displacement (ALH) (MUm;
      amplitude of the lateral head displacement) and straightness (STR) (%,
      straightness) were also estimated. Permanent environmental effects were lower
      than the corresponding values of h(2) and varied between 0.04 and 0.14. Genetic
      correlations between DG and sperm traits showed a high interval of highest
      density of 95% (HPD)(95%) (interval of highest density of 95%). However, there is
      some consistent evidence of the negativity of the genetic correlations of DG with
      NAR and MOT (-0.40 and -0.53, respectively). Permanent correlations were low,
      including the zero in the HPD(95%). Litter birth correlations between DG with LIN
      and STR showed that a favorable effect for growth could be detrimental for them (
      0.47 and -0.53). Therefore, as the magnitude of the genetic correlations does not
      seem very high, it may be possible to define a selection index, including some
      sperm quality traits that allow improvement of DG without diminishing the semen
      quality.

PMID- 22626777
TI  - Effect of holding medium, temperature and time on structural integrity of equine
      ovarian follicles during the non-breeding season.
AB  - The objective was to evaluate the efficiency of phosphate-buffered saline (PBS)
      and Minimum Essential Medium (MEM) during the transport of equine preantral and
      antral follicles at various temperatures and incubation interval. Equine ovaries
      (n = 10) from an abattoir were cut into 19 fragments; one was immediately fixed
      in Bouin's solution (control) and the other fragments were placed in PBS or MEM
      solution at 4, 20, or 39  degrees C for 4, 12, or 24 h. After the respective
      incubation periods, all fragments were fixed in Bouin's solution for 24 h and
      then submitted to standard histologic analysis. In total, 2567 ovarian follicles
      were analyzed, including 1752 primordial, 764 primary, 34 secondary and seven
      antral follicles. Relative to the control group, the transport of equine ovarian
      fragments in both solutions significantly reduced the percentage of
      morphologically normal follicles with increasing time and temperature. At 4 
      degrees C for 4 h, considering primordial and developing follicles, PBS had a
      higher (P < 0.05) rate (98.9%) of morphologically normal follicles than MEM,
      48.7%. At 39  degrees C for 12 h, all follicles in both solutions were
      degenerated. Regarding the stage of follicular development, primordial follicles
      were less (P < 0.05) affected by preservation than primary and secondary
      follicles in all media, times and temperatures tested, except at 4  degrees C for
      12 h in PBS, in which the primary and secondary follicles were less (P < 0.05)
      affected. Overall, 43% of antral follicles were morphologically normal when
      maintained in MEM at 4  degrees C for 4 h. In conclusion, equine follicles were
      successfully preserved in ovarian fragments at 4  degrees C in phosphate-buffered
      saline for up to 4 h.

PMID- 22626778
TI  - Effect of dietary energy on seminal plasma insulin-like growth factor-I (IGF-I),
      serum IGF-I and testosterone levels, semen quality and fertility in adult rams.
AB  - The objective of the present study was to modulate seminal plasma insulin-like
      growth factor-I (IGF-I) by dietary energy and assess the relationship among
      testosterone and IGF-I levels, semen quality and fertility in adult rams. Twenty
      four 1-yr old adult Nellore rams were equally divided into three groups (n = 8)
      and fed with three different concentrate mixtures formulated using conventional
      ingredients and finger millet (Eleucine corocana) straw to ensure rams received
      with similar amount of crude protein with three levels of energy. Rams in low
      energy group were offered diets with 20% less energy than the control energy
      group (optimum energy, 100%, recommended energy level), whereas rams in high
      energy group were offered diets with 20% more energy than the optimum energy
      group. Semen was collected from rams 60 days after start of the experimental
      feeding. The percentages of progressive forward motility, functional membrane
      integrity and mitochondrial membrane potential of the spermatozoa were
      significantly (P < 0.05) higher in control and high energy groups as compared to
      low-energy group. Feeding of low-energy diet significantly (P < 0.05) decreased
      spermatozoa VSL, VCL and VAP when compared to control and high energy fed groups.
      The number of spermatozoa binding/oocyte was significantly (P < 0.05) higher in
      control (11.23 +/- 0.20) and high energy (10.57 +/- 0.19) groups as compared to
      the low energy (6.14 +/- 0.01) group. The serum and seminal plasma IGF-I levels
      were significantly (P < 0.05) higher in control and high energy fed groups as
      compared to the low-energy group. The serum testosterone and cholesterol levels
      were significantly (P < 0.05) higher in the control group as compared to the low
      energy group. The seminal plasma fructose levels in optimum energy fed animals
      were significantly (P < 0.05) higher as compared to other two groups. The seminal
      plasma IGF-I level had positive correlation with progressive forward motility (r
      = 0.7) and other velocity (linearity, r = 0.7; straightness, r = 0.7) parameters.
      The study suggested that the modulation of seminal plasma IGF-I levels by dietary
      energy is possible and the optimum level of seminal plasma IGF-I is necessary and
      sufficient to influence semen quality.

PMID- 22626779
TI  - Direct effect of PGF2alpha pulses on PRL pulses, based on inhibition of PRL or
      PGF2alpha secretion in heifers.
AB  - The relationships between PRL and PGF(2alpha) and their effect on luteolysis were
      studied. Heifers were treated with a dopamine-receptor agonist (bromocriptine;
      Bc) and a Cox-1 and -2 inhibitor (flunixin meglumine [FM]) to inhibit PRL and
      PGF(2alpha), respectively. The Bc was given (Hour 0) when ongoing luteolysis was
      indicated by a 12.5% reduction in CL area (cm(2)) from the area on Day 14
      postovulation, and FM was given at Hours 0, 4, and 8. Blood samples were
      collected every 8-h beginning on Day 14 until Hour 48 and hourly for Hours 0 to
      12. Three groups of heifers in ongoing luteolysis were used: control (n = 7), Bc
      (n = 7), and FM (n = 4). Treatment with Bc decreased (P < 0.003) the PRL
      concentrations averaged over Hours 1 to 12. During the greatest decrease in PRL
      (Hours 2-6), LH concentrations were increased. Progesterone concentrations
      averaged over hours were greater (P < 0.05) in the Bc group than in the controls.
      In the FM group, no PGFM pulses were detected, and PRL concentrations were
      reduced. Concentrations of PGFM were not reduced in the Bc group, despite the
      reduction in PRL. Results supported the hypothesis that a decrease (12.5%) in CL
      area (cm(2)) is more efficient in targeting ongoing luteolysis (63%) than using
      any day from Days 14 to >= 19 (efficiency/day, 10-24%). The hypothesis that PRL
      has a role in luteolysis was supported but was confounded by the known positive
      effect of LH on progesterone. The hypothesis was supported that the synchrony of
      PGFM and PRL pulses represents a positive effect of PGF(2alpha) on PRL, rather
      than an effect of PRL on PGF(2alpha).

PMID- 22626780
TI  - Cortisol and progestin release, heart rate and heart rate variability in the
      pregnant and postpartum mare, fetus and newborn foal.
AB  - The mechanisms leading to parturition in the horse in many aspects differ from
      those in other species. Pregnancy is maintained not by progesterone but by 5alpha
      pregnanes and the progestin precursor pregnenolone originates from the fetus. As
      parturition approaches, the fetal adrenal switches from pregnenolone to cortisol
      synthesis but it is not known whether cortisol crosses the placenta. We
      hypothesized that in parallel to fetal cortisol release, cortisol in the maternal
      circulation increases before foaling and this increase can be determined in both
      saliva and plasma. In addition, maternal, fetal and neonatal heart rate and heart
      rate variability were measured. In 25 pregnant mares, saliva for cortisol
      analysis was collected 4 times daily from 15 days before to 5 days after foaling.
      In 13 mares, in addition, fetomaternal electrocardiogram (ECG) recordings were
      made and blood samples for progestin and cortisol analysis were collected once
      daily. Heart rate (HR) was recorded until 5 days after foaling. The heart rate
      variability (HRV) variables standard deviation of the beat-to-beat (RR) interval
      (SDRR) and root mean square of successive RR differences (RMSSD) were calculated.
      From Days 15 to 4 before parturition, progestin concentration increased (peak 267
      +/- 42 ng/mL) and decreased thereafter (P < 0.05, day of foaling 113 +/- 18
      ng/mL). A prepartum increase in maternal cortisol concentrations was evident in
      blood (P < 0.05) and saliva (P < 0.05) and paralleled the decrease in progestin
      concentrations. In mares, HR remained constant during the last days of pregnancy
      but decreased within one day after parturition (P < 0.05) while maternal HRV did
      not change. In the fetus and neonate, HR increased from before to after birth (P
      < 0.05) indicating increasing demands on the cardiovascular system with
      adaptation to extrauterine life.

PMID- 22626781
TI  - Normal reproductive development of offspring derived by intracytoplasmic
      injection of porcine sperm grown in host mice.
AB  - For establishment of gonadal xenografting, it is essential to clarify whether
      offspring derived from gametes grown in host mice harboring xenografts have
      normal reproductive development. This study examined the secretory profiles of
      gonadal hormones in relation to sexual maturation or ovarian cyclicity in pigs
      generated by intracytoplasmic sperm injection using xenogeneic sperm (Xeno-ICSI
      pigs, four males and one female). We also assessed the developmental activity of
      gametes obtained from these pigs using in vitro culture systems, or by mating
      with conventionally produced (conventional) pigs. During the growth of male Xeno
      ICSI pigs, serum inhibin and testosterone concentrations were generally within
      ranges for those hormones in conventional pigs. Histologically, there were no
      differences in the growth and differentiation of seminiferous tubules between
      Xeno-ICSI and conventional pigs. Parameters of semen quality, including volume,
      pH, sperm concentration, and the percentage of motile sperm were not different
      from those in conventional pigs. Among the Xeno-ICSI pigs, individual differences
      were noted in the ability of sperm to penetrate oocytes and to produce
      blastocysts. However, oocytes after in vitro fertilization using these sperm
      developed into blastocysts containing more than 31 cells. One conventional sow
      delivered 12 piglets after being mated with a male Xeno-ICSI pig. During growth
      of the female Xeno-ICSI pig, serum progesterone concentrations had a sudden
      increase at 41 wk of age, suggesting CL formation. After puberty, this animal
      showed cyclic changes in the serum concentrations of progesterone and inhibin,
      and delivered 10 piglets after AI using fresh sperm obtained from a conventional
      boar. In conclusion, these findings demonstrated that both male and female Xeno
      ICSI pigs had normal reproductive abilities.

PMID- 22626783
TI  - Targeting protein-tyrosine phosphatases in breast cancer.
AB  - In conclusion, we are starting to uncover important activities of PTPs in breast
      cancer initiation, progression and maintenance. Studies of SHP2 and PTP1B have
      exposed them as potentially important targets for the treatment or prevention of
      breast cancer, not to mention the importance of PTP1B in diabetes. However, the
      appropriateness of specific inhibitors has to be fully confirmed, especially
      given the differential involvement of PTPs in an organ-dependent fashion. Crucial
      issues for future studies include the participation of other PTPs in tissue
      development and maintenance as well as cancer, and the signaling networks
      perturbed by PTP inactivation. This approach may lead to the discovery of novel
      signaling mechanisms regulated by PTPs and a better understanding of cancer
      associated pathways.

PMID- 22626782
TI  - Regulation of oocyte mitochondrial DNA copy number by follicular fluid, EGF, and
      neuregulin 1 during in vitro maturation affects embryo development in pigs.
AB  - Little is known about mitochondrial DNA (mtDNA) replication during oocyte
      maturation and its regulation by extracellular factors. The present study
      determined the effects of supplementation of maturation medium with porcine
      follicular fluid (pFF; 0, 10%, 20%, and 30%) on mtDNA copy number and oocyte
      maturation in experiment 1; the effects on epidermal growth factor (EGF; 10
      ng/mL), neuregulin 1 (NRG1; 20 ng/mL), and NRG1 + insulin-like growth factor 1
      (IGF1; 100 ng/mL + NRG1 20 ng/mL), on mtDNA copy number, oocyte maturation, and
      embryo development after parthenogenic activation in experiment 2; and effects on
      embryo development after in vitro fertilization in experiment 3. Overall, mtDNA
      copy number increased from germinal vesicle (GV) to metaphase II (MII) stage
      oocytes after in vitro maturation (GV: 167 634.6 +/- 20 740.4 vs. MII: 275 131.9
      +/- 9 758.4 in experiment 1; P < 0.05; GV: 185 004.7 +/- 20 089.3 vs. MII: 239
      392.8 +/- 10 345.3 in experiment 2; P < 0.05; Least Squares Means +/- SEM).
      Supplementation of IVM medium with pFF inhibited mtDNA replication (266 789.9 +/-
      11 790.4 vs. 318 510.1 +/- 20 377.4; P < 0.05) and oocyte meiotic maturation
      (67.3 +/- 0.7% vs. 73.2 +/- 1.2%, for the pFF supplemented and zero pFF control,
      respectively; P < 0.01). Compared with the control, addition of growth factors
      enhanced oocyte maturation. Furthermore, supplementation of NRG1 stimulated
      mitochondrial replication, increased mtDNA copies in MII oocytes than in GV
      oocytes, and increased percentage of blastocysts in both parthenogenetic and in
      vitro fertilized embryos. In this study, mitochondrial biogenesis in oocytes was
      stimulated during in vitro maturation. Oocyte mtDNA copy number was associated
      with developmental competence. Supplementation of maturation medium with NRG1
      increased mtDNA copy number, and thus provides a means to improve oocyte quality
      and developmental competence in pigs.

PMID- 22626784
TI  - Capturing the signature of single atoms with the tiny probe of a STEM.
AB  - With their first scanning transmission electron microscope (STEM), Albert Crewe
      and his collaborators have succeeded 40 years ago in bringing to reality a dream
      for all electron microscopists, to see individual atoms. In the derivation of
      Crewe's pioneering work, the present review describes various historical and
      present steps, involving continuous instrumental and methodological developments
      as well as the preparation of suitable specimens. They have lead to the
      identification of individual atoms by electron energy-loss spectroscopy (EELS)
      and to the demonstration of atom-by-atom spectroscopy. Beyond these spectacular
      successes which open wide fields of use, most recent technical achievements, such
      as the introduction of monochromators on the incident electron beam or of optical
      spectrometers for recording spectra (in the visible as well as in the X-ray
      domain), will undoubtedly lead to refine the accessible signature of single atoms
      and molecules.

PMID- 22626785
TI  - Minimal residual disease in myeloma: are we there yet?
AB  - Measurement of minimal residual disease is routine in diseases such as chronic
      myelogenous leukemia, precursor B cell acute lymphoblastic leukemia, and acute
      promyelocytic leukemia because it provides important prognostic information.
      However, the role of minimal residual disease testing has not been widely adopted
      in multiple myeloma (MM), with other parameters such as the International Staging
      System (ISS) and cytogenetic analysis primarily guiding therapy and determination
      of prognosis. Until recently, achieving a complete response (CR), as defined by
      the International Myeloma Working Group (IMWG) criteria, was rare in patients
      with MM. The use of novel agents with or without autologous peripheral blood stem
      cell transplantation (auto-PBSCT) has significantly increased CR rates, thus
      increasing overall survival (OS) rates. The majority of patients with MM have
      persistent levels of residual disease that are below the sensitivity of bone
      marrow (BM) morphology, protein electrophoresis with immunofixation, and light
      chain quantitation even after attaining CR and will eventually relapse.
      Measurement of minimal residual disease by more sensitive methods, and the use of
      these methods as a tool for predicting patient outcomes and guiding therapeutic
      decisions, has thus become more relevant. Methods available for monitoring
      minimal residual disease in MM include PCR and multiparameter flow cytometry
      (MFC), both of which have been shown to be valuable in other hematologic
      malignancies; however, neither has become a standard of care in MM. Here, we
      review current evidence for using minimal residual disease measurement for risk
      assessment in MM as well as incorporating pretreatment factors and posttreatment
      minimal residual disease monitoring as a prognostic tool for therapeutic
      decisions, and we outline challenges to developing uniform criteria for minimal
      residual disease monitoring.

PMID- 22626786
TI  - Promoter methylation of esophageal cancer-related gene 4 in gastric cancer tissue
      and its clinical significance.
AB  - BACKGROUND/AIMS: To observe the promoter methylation of esophageal cancer-related
      gene 4 (ECRG4) in gastric cancer tissues and explore its clinical significance.
      METHODOLOGY: ECRG4 promoter methylation was detected with methylation-specific
      PCR in 49 samples of gastric cancer tissues, 30 samples of peri-cancerous tissues
      and 15 samples of normal tissues. The relations of ECRG4 promoter methylation to
      pathology, age, gender and lymph node metastasis were analyzed. RESULTS: The rate
      of ECRG4 promoter methylation was higher in gastric cancer tissues (69.4%
      (34/49)) and peri-cancerous tissues (53.3% (16/30)) than in normal tissues (6.7%
      (1/15)) (p<0.01). The rate of ECRG4 promoter methylation was higher in stage
      III+IV (80% (24/30)) than in stage I+II gastric cancer tissues (52.6% (10/19))
      (p<0.05). The rate of ECRG4 promoter methylation was not related to age, gender
      and lymph node metastasis (all p>0.05). CONCLUSIONS: Aberrant ECRG4 promoter
      methylation may be used to monitor early gastric cancer and predict pathological
      staging. ECRG4 may become a molecular therapeutic target against gastric cancer.

PMID- 22626787
TI  - Meta-analysis of randomized controlled trials on laparoscopic gastrectomy vs.
      open gastrectomy for distal gastric cancer.
AB  - BACKGROUND/AIMS: To evaluate the safety and practicability of laparoscopic
      gastrectomy (LG) by comparing the short-term and long-term outcomes of LG and
      open gastrectomy (OG) for gastric cancer. METHODOLOGY: According to the
      criterion, randomized clinical trials (RCTs) were searched in MEDLINE, EMBASE,
      CNKI (in Chinese), WANFANG DATA (in Chinese), and Cochrane Controlled Trials
      Register from January 2000 to January 2012. The RCTs were prepared in accordance
      with the quality of reporting of meta-analyses statement. Intraoperative and
      early postoperative parameters, as well as long-term tumor recurrence were
      analyzed. Random effect meta-analyses were performed using odds ratios (ORs) and
      weighted mean differences (WMDs). RESULTS: Up to 8 RCTs with 782 patients were
      enrolled in the present meta-analysis (402 patients underwent LG (LG group) and
      380 underwent OG (OG group)). The LG group had shorter wound lengths, less blood
      loss, more rapid bowel function recovery: first flatus and first food intake,
      lower overall complication rate and shorter hospital stay, whereas the LG group
      had longer operation times and less harvested lymph nodes. The tumor recurrence
      between the two groups had no significant difference. CONCLUSIONS: Considering
      its lower morbidity and enhanced postoperative recovery, LG is a safe technical
      alternative to OG for distal gastric cancer.

PMID- 22626788
TI  - [A rash].

PMID- 22626789
TI  - Developmental plasticity in metabolic rates reinforces morphological plasticity
      in response to social cues of sexual selection.
AB  - Developmental plasticity allows individuals to match their phenotype to the
      competitive environment they are most likely to encounter. Although there are
      numerous studies that demonstrate adaptive shifts in life-history and metric
      traits, we still have a poor understanding of whether internal physiological
      processes demonstrate plasticity and whether this plasticity supports life
      history and metric traits. Here we use the Australian redback spider (Latrodectus
      hasselti), a species that demonstrates adaptive developmental shifts in response
      to the availability of females and the density of males, to examine the
      relationship between the routine metabolic rate (RMR) and the expression of size,
      body-condition and development rate. We reared immature males in three diet
      treatments, and in social environments that varied the presence/absence of
      females and the density of males and measured their RMR, weight, size and
      developmental rate at maturity. We show that although RMR decreased with
      decreasing resource abundance, RMR was positively correlated with the density of
      rivals. Moreover, RMR was not correlated with size or body-condition at maturity.
      Our results demonstrate that plasticity in the RMR supports plasticity in metric
      and life-history traits to create an integrated phenotype that matches the
      competitive environment.

PMID- 22626790
TI  - Honeybees - superstars for all types of education.

PMID- 22626791
TI  - Copulation is necessary for the completion of a gonotrophic cycle in the tick
      Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae).
AB  - Ovarian development and egg maturation are essential stages in animal
      reproduction. For bisexual ixodid ticks, copulation is an important prerequisite
      for the completion of the gonotrophic cycle. In this study, we aimed to
      characterize the morpho-histological changes in the ovary and oocytes of the tick
      Rhipicephalus sanguineus, together with the identification of feeding and
      reproductive parameters associated with mating. Virgin and cross-mated females
      (with R. turanicus males) weighed 60% less at full engorgement than females mated
      conspecifically. In addition, the oocytes of these females did not develop to the
      same advanced stages as those of the conspecifically mated females. Sequencing of
      a 250-bp ITS-2 fragment in eggs that originated from a cross between an R.
      sanguineus female and an R. turanicus male showed a genotype similar (except by a
      deletion of 1 thymine) to that observed in the mother, arguing against
      fertilization by a trans-specific male. These findings suggest that male sex
      peptides are species-specific molecules that influence both full engorgement and
      oocyte maturation. Mechanical stimulation of the gonopore alone was insufficient
      for the completion of the entire process of vitellogenesis.

PMID- 22626792
TI  - The fate of follicles after a blood meal is dependent on previtellogenic
      nutrition and juvenile hormone in Aedes aegypti.
AB  - Juvenile hormone (JH) mediates the relationship between fecundity and nutrition
      during the gonotrophic cycle of the mosquito in three ways: (1) by regulating
      initial previtellogenic development, (2) by mediating previtellogenic resorption
      of follicles and (3) by altering intrinsic previtellogenic follicle "quality",
      physiology, and competitiveness thereby predetermining the fate of follicles
      after a blood meal. To support a role for JH in mediating the response of ovarian
      follicles after a blood meal, we explored three main questions: (1) Do changes in
      nutrition during the previtellogenic resting stage lead to relevant biochemical
      and molecular changes in the previtellogenic ovary? (2) Do hormonal manipulations
      during the previtellogenic resting stage lead to the same biochemical and
      molecular changes? (3) Does nutrition and hormones during the previtellogenic
      resting stage affect vitellogenic resorption and reproductive output? We examined
      the accumulation of neutral lipids in the previtellogenic ovary as well as the
      previtellogenic expression of genes integral to endocytosis and oocyte
      development such as the: vitellogenin receptor (AaVgR), lipophorin receptor
      (AaLpRov), heavy-chain clathrin (AaCHC), and ribosomal protein L32 (rpL32) under
      various previtellogenic nutritional and hormonal conditions. mRNA abundance and
      neutral lipid content increased within the previtellogenic ovary as
      previtellogenic mosquitoes were offered increasing sucrose concentrations.
      Methoprene application mimicked the effect of offering the highest sucrose
      concentrations on mRNA abundance and lipid accumulation in the previtellogenic
      ovary. These same nutritional and hormonal manipulations altered the extent of
      vitellogenic resorption. Mosquitoes offered 20% sucrose during the
      previtellogenic resting stage had nearly 3 times less vitellogenic resorption
      than mosquitoes offered 3% sucrose despite taking smaller blood meals and
      developed ~10% more eggs during the first gonotrophic cycle. Mosquitoes treated
      with JH III during the previtellogenic resting stage and then offered a blood
      meal had a ~40% reduction in the amount of vitellogenic resorption and developed
      ~12% more eggs. Taken together, these results suggest that previtellogenic
      nutrition alters the extent and pattern of resorption after a blood meal through
      the effect of JH on mRNA abundance and lipid accumulation in previtellogenic
      follicles.

PMID- 22626793
TI  - What improves minimal hepatic encephalopathy: probiotic yogurt, protein
      restriction or nonabsorbable disaccharides?

PMID- 22626795
TI  - Lactulose for minimal hepatic encephalopathy in patients with extrahepatic portal
      vein obstruction.
AB  - BACKGROUND/AIMS: Minimal hepatic encephalopathy (MHE) is common in patients with
      extrahepatic portal vein obstruction (EHPVO). There is no study on the treatment
      of MHE using lactulose in patients with EHPVO. PATIENTS AND METHODS: Consecutive
      EHPVO patients were assessed by psychometric (number connection test (NCT-A and
      B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), and
      critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were
      treated with lactulose and psychometric tests, CFF, and were reassessed after 3
      months. RESULTS: Of the 70 patients screened, the prevalence of abnormal
      psychometric test was as follows: NCT-A (41%), NCT-B (53%), DST (38%), SDT (40%),
      and LTT (44%). Thirty patients (43%) had two or more than two abnormal (>2 SD)
      psychometry tests. Lactulose improved MHE in 16/30 (53%) of patients after 3
      months of treatment. Arterial ammonia decreased after lactulose treatment
      compared to baseline (83.7+/-19.1 vs. 65.1+/-19.3 MUmol/l, P=0.001). A total of 9
      (75%) of 12 patients with large spontaneous shunt and 7 (39%) of 18 patients
      without spontaneous shunt improved with lactulose (P=0.07). CFF in patients with
      MHE (n=30) was significantly lower than those without MHE (n=40) (38.1+/-2.4 vs.
      41.5+/-3.1 Hz, P=0.01). CFF was less than 38 Hz in 21 (70%) of 30 patients before
      treatment and in 10 (33%) patients after lactulose therapy in MHE patients. All
      patients could tolerate lactulose without any significant side effects. Four
      patients (13%) developed transient diarrhea in whom dose needed reduction, 3
      (10%) did not like its taste but have continued, and 2 (6%) developed abdominal
      bloating sensation. CONCLUSIONS: Lactulose is effective in the treatment of MHE
      in patients with EHPVO.

PMID- 22626796
TI  - Knowledge, attitudes, and practices of primary care physicians about irritable
      bowel syndrome in Northern Saudi Arabia.
AB  - BACKGROUND/AIM: Primary health care (PHC) physicians manage most patients with
      irritable bowel syndrome (IBS). In Saudi Arabia, there are limited data on their
      knowledge, attitudes, and practices about this disorder. This study aimed to
      assess knowledge, attitudes, and practices of primary care physicians about IBS.
      PATIENTS AND METHODS: A cross-sectional survey of 70 practitioners aged 36 +/-
      10.25 years was carried out in primary care centers in AlJouf Province of Saudi
      Arabia. The physicians were asked to fill a valid questionnaire containing their
      sociodemographic data, and well-modified questions regarding their knowledge,
      attitudes, and practices about IBS. Data was processed and analyzed using SPSS
      (version 15) program, and the level of significance was set at P<0.05. RESULTS: A
      response rate of 92.9% yielded 65 questionnaires for analysis. Majority of
      physicians surveyed (83.1%) considered IBS as a common health problem in Saudi
      Arabia, and (55.4%) believed it is underestimated. There was a significant
      association between physicians' qualifications and using diagnostic tools to
      facilitate IBS diagnosis (14.3% vs 35.5%; P<0.05), while utilization of "Rome or
      Manning criteria" was more frequent by physicians with master's degree (35.5%)
      compared to residents (14.3%). Also, 35.4% of physicians (15 males and 8 females)
      were not sure how to diagnose IBS. CONCLUSIONS: This study suggested that PHC
      physicians had a suitable attitude toward IBS, but they lacked knowledge, and
      their practices toward this condition were inappropriate.

PMID- 22626797
TI  - Therapeutic effect of captopril, pentoxifylline, and cordyceps sinensis in pre
      hepatic portal hypertensive rats.
AB  - BACKGROUND/AIM: Portal hypertension is an important and potentially fatal
      complication of liver disease whereby cellular and fibrotic alterations manifest
      to increase portal venous pressure. The aim of this study is to investigate the
      effect of captopril, pentoxifylline (PTX), and cordyceps sinensis in pre-hepatic
      portal hypertensive rats. SETTINGS AND DESIGN: Wistar male rats were divided at
      random into 3 main groups: the first group: control rats. The second group: sham
      operated rats and the third group: prehepatic portal hypertensive rats (PHPHT)
      induced by regulated pre-hepatic portal vein ligation. After 14 days, Group 3 was
      subdivided into 5 subgroups. Subgroup (1): portal vein-ligated (PVL) was killed
      at once; Subgroup (2): received distilled water for 30 days (untreated PVL
      group); subgroups 3-5 were treated with captopril (60 mg/kg, orally); PTX (100
      mg/kg, orally); and C. sinensis (200 mg/kg, orally), respectively, as a single
      daily dose for 30 days. PATIENTS AND METHODS: Portal pressure, nitric oxide (NO),
      antioxidant enzymes, Liver enzymes, and creatinine levels were measured to
      evaluate the status of the liver state. RESULTS: Portal vein ligation produced
      significant increments in liver enzymes, NO, creatinine and portal pressure
      concomitant with significant decrements in glutathione content and superoxide
      dismutase activity. Treatment with captopril, PTX, and C. sinensis resulted in a
      significant reduction in liver enzymes, NO, creatinine and portal pressure and
      observable increase in antioxidant enzymes. CONCLUSIONS: captopril, PTX, and C.
      sinensis have promising effect in controlling PHPHT and reducing hyperdynamic
      circulatory state through reduction of portal pressure and NO level.

PMID- 22626794
TI  - Understanding the mechanism of hepatic fibrosis and potential therapeutic
      approaches.
AB  - Hepatic fibrosis (HF) is a progressive condition with serious clinical
      complications arising from abnormal proliferation and amassing of tough fibrous
      scar tissue. This defiance of collagen fibers becomes fatal due to ultimate
      failure of liver functions. Participation of various cell types, interlinked
      cellular events, and large number of mediator molecules make the fibrotic process
      enormously complex and dynamic. However, with better appreciation of underlying
      cellular and molecular mechanisms of fibrosis, the assumption that HF cannot be
      cured is gradually changing. Recent findings have underlined the therapeutic
      potential of a number of synthetic compounds as well as plant derivatives for
      cessation or even the reversal of the processes that transforms the liver into
      fibrotic tissue. It is expected that future inputs will provide a conceptual
      framework to develop more specific strategies that would facilitate the
      assessment of risk factors, shortlist early diagnosis biomarkers, and eventually
      guide development of effective therapeutic alternatives.

PMID- 22626798
TI  - The protective role of Aegle marmelos on aspirin-induced gastro-duodenal
      ulceration in albino rat model: a possible involvement of antioxidants.
AB  - BACKGROUND/AIM: Gastro duodenal ulcer is a common disorder of the
      gastrointestinal tract. Several Indian medicinal plants have been traditionally
      and extensively used to prevent different diseases. In the present research
      studies, Bael fruit (Aegle marmelos (AM), family: Rutaceae) which are also called
      as Bilva in ancient Sanskrit was used as a herbal drug and its antioxidative role
      in aspirin- induced gastroduodenal ulceration in albino rat was evaluated using
      essential biochemical parameters. PATIENTS AND METHODS: Mucosal thickness (MT),
      ulcer index (UI), different biochemical parameters, such as aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), catalase (CAT),
      superoxide dismutase (SOD), reduced glutathione (GSH), and lipid peroxidation
      (LPO) were measured in all the groups, to study the possible involvement of
      antioxidants with gastroduodenal protection. RESULTS: A significant decrease in
      MT, SOD and CAT activities and GSH level and a significant increase in UI, AST,
      ALT, and ALP activities and LPO level were observed in aspirin treated stomach
      and duodenum of albino rats. CONCLUSIONS: Pretreatment with AM fruit pulp extract
      for 14 consecutive days showed the reverse effects of aspirin suggesting gastro
      duodenal protective and anti- ulcerogenic properties of AM through its
      antioxidant mechanism.

PMID- 22626799
TI  - Comparison of quality of life in patients undergoing transhiatal esophagectomy
      with or without chemotherapy.
AB  - BACKGROUND/AIM: To compare the quality of life (QOL) in patients undergoing
      transhiatal esophagectomy (THE) with or without chemotherapy, who were admitted
      to the Post Graduate Institute of Medical Education and Research, Chandigarh and
      enrolled in the study, from July 2004 to October 2005. PATIENTS AND METHODS:
      Thirty patients of esophageal carcinoma by purposive sampling were randomized
      into two groups i.e., patients undergoing THE after chemotherapy and patients
      undergoing THE without chemotherapy. Two QOL questionnaires, one generic i.e.,
      EORTC-QLQ C-30 (European Organization for Research and Treatment of Cancer) and
      other esophageal cancer-specific i.e., EORTC OES-18 were utilized to assess the
      QOL. RESULT: Physical functional scales were better in patients, who received
      neoadjuvant chemotherapy. The role and social aspects of functional scales
      deteriorated after completion of treatment in both groups. This was primarily due
      to the effect of surgery. However, they were better from an emotional and
      cognitive point of value after surgery and radiotherapy. Fourteen out of 30
      patients experienced vomiting and diarrhea due to radiotherapy. CONCLUSION: THE
      in esophageal carcinoma improves global health scales and majority of symptom
      scales in all patients. QOL improvement in general was better in patients who
      were administered neoadjuvant chemotherapy along with surgery.

PMID- 22626800
TI  - Frequency of low bone mineral density in Saudi patients with inflammatory bowel
      disease.
AB  - BACKGROUND/AIMS: Metabolic bone disease is common in patients with inflammatory
      bowel disease (IBD). Our aim was to determine the frequency of bone loss among
      Saudi patients with IBD and possible contributing risk factors. SETTINGS AND
      DESIGN: We retrospectively reviewed Saudi patients with IBD, between 18 and 70
      years of age, who had bone mass density (BMD) determined by dual-energy X-ray
      absorptiometry scanning at one of three hospitals in the Kingdom of Saudi Arabia
      from 2001 to 2008. PATIENTS AND METHODS: Case notes and BMDs results were
      carefully reviewed for demographic and clinical data. Low bone mass, osteopenia,
      and osteoporosis were defined according to the WHO guidelines. STATISTICAL
      ANALYSIS USED: Predictive factors for BMD were analyzed using group comparisons
      and stepwise regression analyses. RESULTS: Ninety-five patients were included;
      46% had Crohn's disease (CD) and 54% had ulcerative colitis (UC). The average age
      was 30.9+/-11.6 years. Using T-scores, the frequency of osteopenia was 44.2%, and
      the frequency of osteoporosis was 30.5% at both lumbar spine and proximal femur.
      Only 25.3% of patients exhibited a BMD within the normal range. Our results
      revealed a positive correlation between the Z-score in both the lumbar spine and
      the proximal femur and body mass index (BMI) (P=0.042 and P=0.018, respectively).
      On regression analysis BMI, age, and calcium supplementation were found to be the
      most important independent predictors of BMD. CONCLUSIONS: Saudi patients with
      IBD are at an increased risk of low BMD and the frequency of decreased BMD in
      Saudi patients with CD and UC were similar. BMI and age were the most important
      independent predictors of low BMD.

PMID- 22626801
TI  - Perinatal cytomegalovirus hepatitis in Saudi infants: a case series.
AB  - BACKGROUND/AIM: Cytomegalovirus (CMV) is the most common congenital viral
      infection, occurring in 0.4%-2.3% of all live births. The clinical manifestations
      of CMV are multiorgan involvement. Currently, the numbers of studies of hepatic
      CMV infection in immunocompetent infants are insufficient and little information
      exists in the medical literature about the hepatic manifestations and
      complications of CMV. PATIENTS AND METHODS: Nine infants diagnosed with hepatic
      CMV infection were included in the study. The diagnosis was based on the presence
      of IgM anti-CMV antibodies titer in serum and detection of CMV-DNA in blood. The
      authors identified clinical characteristics, biochemical characteristics,
      immunologic markers, and the outcome of hepatic CMV with or without treatment.
      RESULTS: Jaundice was the most common clinical feature of CMV infection in
      infancy (100%). Hepatic abnormalities in the form of cholestasis (defined as a
      serum conjugated bilirubin concentration greater than 17.1 MUmol/L or greater
      than 20% of the total serum bilirubin) were found in all patients (100%),
      hepatitis (77%), hypoalbuminemia (55%), elevated alkaline phosphatase, and gamma
      glutamyltransferase (77%). Other findings showed hepatosplenomegaly (44%),
      thrombocytopenia (22%) and low birth weight (11%) The treatment of hepatic CMV
      infection was indicated in 66% and was not indicated in 33%. Both of them had
      resolved cholestasis and hepatitis. CONCLUSION: Jaundice and cholestasis were the
      most common clinical features of hepatic CMV infections. Hepatic CMV infection in
      young infants is often a self-limited illness that does not require antiviral
      therapy. Most of the patients with hepatic CMV infection had a favorable outcome.

PMID- 22626802
TI  - Hepatic-associated immunoglobulin-A nephropathy in a child with liver cirrhosis
      and portal hypertension.
AB  - Hepatic-associated immunoglobulin A (IgA) nephropathy is a relatively common
      condition that occurs in adults with liver cirrhosis and portal hypertension.
      However, it is rare in children. This condition is characterized by the
      deposition of IgA in the renal glomeruli. The present report describes a 14-year
      old boy with cryptogenic liver cirrhosis and portal hypertension who presented
      with hematuria and proteinuria associated with histological changes of IgA
      nephropathy.

PMID- 22626803
TI  - Seroconversion of hepatitis B envelope antigen (HBeAg) by entecavir in a child
      with chronic hepatitis B.
AB  - Hepatitis B virus (HBV) infection is a worldwide health problem. Consensus
      guidelines for the treatment of chronic HBV in children have not been
      established, and indications for antiviral therapy in adults with chronic HBV
      infection may not be applicable to children. The medications that are Food and
      Drug Administration approved for the treatment of children with HBV include
      interferon (IFN)-alpha and lamivudine. Nondetectable serum HBV deoxyribonucleic
      acid, Hepatitis B envelope antigen (HBeAg) loss, and HBeAg seroconversion
      following 1 year duration of entecavir treatment. A review of the literature of
      entecavir treatment of chronic hepatitis B in children is also provided.

PMID- 22626804
TI  - Endoscopic management for delayed diagnosis of a foreign body penetrating the
      esophagus into the lung.
AB  - A 31-year-old male presented with chest pain started after eating chicken about 2
      weeks earlier. Upper endoscopy and Computed tomography scan of the chest revealed
      a sharp chicken bone penetrating the esophageal wall into the right lung. The
      foreign body was removed endoscopically using a rat-tooth forceps, followed by
      prophylactic placement of a metal stent across the esophageal perforation site.
      Foreign body-induced perforation is one of the common etiologies of benign
      esophageal perforations. Although the primary treatment is surgery, endoscopic
      therapy may be appropriate in individualized cases like our patient.

PMID- 22626805
TI  - Dilated biliary system. Type-1A choledochal cyst with cholalgocarcinoma.

PMID- 22626806
TI  - Epigenetic regulation of cancer stem cell genes in triple-negative breast cancer.
AB  - Expression of specific breast cancer stem cells (BCSCs) is seen in aggressive
      tumors, but their regulation is unclear. Epigenetic changes influence gene
      expression and are implicated in breast cancer progression. We hypothesized that
      promoter methylation regulates specific BCSC-related genes [CD44, CD133, CD24,
      MSH1 (alias, Musashi-1), and ALDH1] and that this epigenetic profile can identify
      aggressive subtypes, such as triple-negative breast cancer (TNBC). Methylation
      analysis was performed using MassARRAY EpiTYPER sequencing; CpG-rich sites were
      identified in the promoter regions of BCSC genes, except ALDH1. These sites were
      screened by treatment with 5-aza-2'-deoxycytidine in four TN and five non-TNBC
      cell lines. The specific regulatory CpG site demonstrating the most significant
      inverse correlation between CpG site methylation and mRNA expression was
      identified for CD44, CD133, and Musashi-1, but not for CD24. Methylation of CD44,
      CD133, and Musashi-1 was evaluated in 91 American Joint Committee on Cancer stage
      I to III primary breast cancer tumors, and these sites were significantly
      hypomethylated in TNBC versus non-TNBC. The IHC staining of primary tumors with
      the highest and lowest methylation levels revealed the strongest staining in
      hypomethylated specimens, suggesting that hypomethylation leads to gene
      activation. We demonstrate that methylation is a significant mechanism regulating
      CD44, CD133, and Musashi-1, and that gene hypomethylation correlates with TNBC.
      Assessment of epigenetic changes in BCSC genes may provide a more accurate
      classification of TNBC and could be developed as potential therapeutic targets.

PMID- 22626808
TI  - Matrix metalloproteinase 2 of grass carp Ctenopharyngodon idella (CiMMP2) is
      involved in the immune response against bacterial infection.
AB  - The gene encoding matrix metalloproteinase 2 (MMP2) was cloned from grass carp
      (Ctenopharyngodon idella), and its expression levels during Aeromonas hydrophila
      infection and embryonic development stages were evaluated. The complete open
      reading frame of CiMMP2 was 1974 bp in length, encoding a 658-amino acid
      polypeptide. The deduced MMP2 protein contained four conserved domain structures,
      including an N-terminal signal sequence, a propeptide domain, three repeats of
      fibronectin-type II domain inserted in the catalytic domain and a C-terminal
      hemopexin-like domain. Phylogenetic analysis of MMP2s grouped grass carp with
      other teleosts. Detected in all fish tissues examined, CiMMP2 expression
      increased in the spleen and head kidney at 4 h and was significantly
      downregulated at 1 d after A. hydrophila infection. CiMMP2 transcripts were
      present in unfertilized eggs, suggesting its maternal origin. These findings
      implicate an important role for CiMMP2 in A. hydrophila-related diseases and
      early embryonic developmental stages of grass carp.

PMID- 22626809
TI  - Characterization of skin ulceration syndrome associated microRNAs in sea cucumber
      Apostichopus japonicus by deep sequencing.
AB  - MicroRNAs (miRNAs) constitute a family of small RNA species which have been
      demonstrated to be one of key effectors in mediating host-pathogen interaction.
      In this study, two haemocytes miRNA libraries were constructed with deep
      sequenced by illumina Hiseq2000 from healthy (L1) and skin ulceration syndrome
      Apostichopus japonicus (L2). The high throughput solexa sequencing resulted in
      9,579,038 and 7,742,558 clean data from L1 and L2, respectively. Sequences
      analysis revealed that 40 conserved miRNAs were found in both libraries, in which
      let-7 and mir-125 were speculated to be clustered together and expressed
      accordingly. Eighty-six miRNA candidates were also identified by reference genome
      search and stem-loop structure prediction. Importantly, mir-31 and mir-2008
      displayed significant differential expression between the two libraries according
      to FPKM model, which might be considered as promising targets for elucidating the
      intrinsic mechanism of skin ulceration syndrome outbreak in the species.

PMID- 22626807
TI  - Type 1 interferons suppress accelerated osteoclastogenesis and prevent loss of
      bone mass during systemic inflammatory responses to Pneumocystis lung infection.
AB  - HIV infection causes loss of CD4(+) T cells and type 1 interferon (IFN)-producing
      and IFN-responsive dendritic cells, resulting in immunodeficiencies and
      susceptibility to opportunistic infections, such as Pneumocystis. Osteoporosis
      and bone marrow failure are additional unexplained complications in HIV-positive
      patients and patients with AIDS, respectively. We recently demonstrated that mice
      that lack lymphocytes and IFN a/b receptor (IFrag(-/-)) develop bone marrow
      failure after Pneumocystis lung infection, whereas lymphocyte-deficient, IFN
      alpha/beta receptor-competent mice (RAG(-/-)) had normal hematopoiesis.
      Interestingly, infected IFrag(-/-) mice also exhibited bone fragility, suggesting
      loss of bone mass. We quantified bone changes and evaluated the potential
      connection between progressing bone fragility and bone marrow failure after
      Pneumocystis lung infection in IFrag(-/-) mice. We found that Pneumocystis
      infection accelerated osteoclastogenesis as bone marrow failure progressed. This
      finding was consistent with induction of osteoclastogenic factors, including
      receptor-activated nuclear factor-kappaB ligand and the proapoptotic factor tumor
      necrosis factor-related apoptosis-inducing ligand, in conjunction with their
      shared decoy receptor osteoprotegerin, in the bone marrow of infected IFrag(-/-)
      mice. Deregulation of this axis has also been observed in HIV-positive
      individuals. Biphosphonate treatment of IFrag(-/-) mice prevented bone loss and
      protected loss of hematopoietic precursor cells that maintained activity in vitro
      but did not prevent loss of mature neutrophils. Together, these data show that
      bone loss and bone marrow failure are partially linked, which suggests that the
      deregulation of the receptor-activated nuclear factor-kappaB
      ligand/osteoprotegerin/tumor necrosis factor-related apoptosis-inducing ligand
      axis may connect the two phenotypes in our model.

PMID- 22626810
TI  - Modulation of the innate immune system in white shrimp Litopenaeus vannamei
      following long-term low salinity exposure.
AB  - Immune parameters, haemocyte lifespan, and gene expressions of lipopolysaccharide
      and beta-glucan-binding protein (LGBP), peroxinectin (PX), integrin beta, and
      alpha2-macroglobulin (alpha2-M) were examined in white shrimp Litopenaeus
      vannamei juveniles (0.48 +/- 0.05 g) which had been reared at different salinity
      levels of 2.50/00, 50/00, 150/00, 250/00, and 350/00 for 24 weeks. All shrimp
      survived during the first 6 weeks. The survival rate of shrimp reared at 2.50/00
      and 50/00 was much lower (30%) than that of shrimp reared at 150/00, 250/00, and
      350/00 (76%~86%) after 24 weeks. Shrimp reared at 25% grew faster. Shrimp reared
      at 2.50/00 and 50/00 showed lower hyaline cells (HCs), granular cells (GCs),
      phenoloxidase activity (PO) activity, respiratory bursts (RBs), superoxide
      dismutase (SOD) activity, and lysozyme activity, but showed a longer haemocyte
      lifespan, and higher expressions of LGBP, PX, integrin beta, and alpha2-M. In
      another experiment, shrimp which had been reared at different salinity levels for
      24 weeks were challenged with Vibrio alginolyticus (6 * 10(6) cfu shrimp(-1)),
      and WSSV (10(3) copies shrimp(-1)) and then released to their respective
      seawater. At 96-144 h, cumulative mortalities of shrimp reared at 2.50/00 and
      50/00 were significantly higher than those of shrimp reared at 150/00, 250/00,
      and 350/00. It was concluded that following long-term exposure to 2.50/00 and
      50/00 seawater, white shrimp juveniles exhibited decreased resistance against a
      pathogen due to reductions in immune parameters. Increases in the haemocyte
      lifespan and gene expressions of LGBP, integrin beta, PX, and alpha2-M indicated
      that shrimp had the ability to expend extra energy to modulate the innate immune
      system to prevent further perturbations at low salinity levels.

PMID- 22626811
TI  - Subcellular localization and functional characterization of a fish IRF9 from
      crucian carp Carassius auratus.
AB  - Mammalian interferon (IFN) regulatory factor 9 (IRF-9) has long been recognized
      as the DNA sequence recognition subunit of IFN-stimulated gene factor 3 (ISGF3)
      complex, which is critical for type I IFN to induce the expression of IFN
      stimulated genes (ISGs) against viral infection. Recent studies have shown that
      fish IFN exerts antiviral effects by induction of a number of ISGs and also of
      itself; however, little is known about the role of fish IRF9 in IFN signaling.
      Here we identify a fish IRF9 orthologue (CaIRF9) from IFN-producing cell line,
      crucian carp Carassius auratus blastulae embryonic (CAB) cells. Analysis of
      subcellular distribution of CaIRF9-green fluorescent protein indicates that
      CaIRF9 is constitutively present in the nucleus, which is driven by two nuclear
      localization signals (NLS), one locating within DNA-binding domain (DBD) of
      CaIRF9 and the other immediately behind DBD, although human IRF9 contains only
      one NLS analogous to the former of CaIRF9. Overexpression of CaIRF9 together with
      CaSTAT2 not only activates ISRE-containing promoter but also upregulates the
      expression of fish ISGs. Strikingly, CaIRF9 together with CaSTAT2 also exhibits
      an ability to activate crucian carp IFN promoter, and blockade of cellular CaIRF9
      attenuates IFN itself-induced activation of crucian carp IFN promoter. Taken
      together, these data suggest that crucian carp IFN induces the expression of ISGs
      and also of itself possibly by the JAK-STAT signaling pathway that is conserved
      from fish to mammals.

PMID- 22626812
TI  - The use of the finasteride-adjusted Prostate Cancer Prevention Trial Prostate
      Cancer Risk Calculator in a Mexican referral population: a validation study.
AB  - OBJECTIVES: To perform the first validation study of the finasteride-adjusted
      Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (finPCPTRC) in a
      contemporary referral population in Mexico. METHODS: 837 patients referred to the
      Instituto Nacional de Cancerologia, Mexico City, Mexico, between 2005 and 2009
      were used to validate the finPCPTRC by examining various measures of
      discrimination and calibration. Net benefit curve analysis was used to gain
      insight into the use of the finPCPTRC for clinical decisions. RESULTS: Prostate
      cancer (PCa) incidence (72.8%) was high in this Mexican referral cohort and 45.7%
      of men who were diagnosed with PCa had high-grade lesions (HGPCa, Gleason score
      >6). 1.3% of the patients were taking finasteride. The finPCPTRC was a superior
      diagnostic tool compared to prostate-specific antigen alone when discriminating
      patients with PCa from those without PCa (AUC = 0.784 vs. AUC = 0.687, p < 0.001)
      and when discriminating patients with HGPCa from those without HGPCa (AUC = 0.768
      vs. AUC = 0.739, p < 0.001). The finPCPTRC underestimated the risk of PCa but
      overestimated the risk of HGPCa (both p < 0.001). Compared with other strategies
      to opt for biopsy, the net benefit would be larger with utilization of the
      finPCPTRC for patients accepting higher risks of HGPCa. CONCLUSIONS: Rates of
      biopsy-detectable PCa and HGPCa were high and 1.3% of this referral cohort in
      Mexico was taking finasteride. The risks of PCa or HGPCa calculated by the
      finPCPTRC were not well calibrated for this referral Mexican population and new
      clinical diagnostic tools are needed.

PMID- 22626813
TI  - The effects of prewarming the I-gel on fitting to laryngeal structure.
AB  - PURPOSE: The supraglottic airway, I-gel (Intersurgical, Wokingham, United
      Kingdom), has a noninflatable cuff, which softens at body temperature to fit to
      laryngeal structure. The present study was performed to investigate the
      hypothesis that the cuff of I-gel can fit to laryngeal structure faster when
      prewarmed to body temperature than kept at room temperature. METHODS: A total of
      180 adult patients were assigned to the warm group (90 patients) or the control
      group (90 patients). Anesthesia was induced with propofol, remifentanil, or
      fentanyl. Vecuronium or rocuronium was administered as a muscle relaxant. The I
      gel was warmed to 37  degrees C before insertion in the warm group and it was in
      the room temperature (approximately 20  degrees C) in the control group.
      Insertion time, number of attempt for successful insertion, inspiratory pressure,
      leak pressure, and leak volume were compared between the 2 groups. RESULTS:
      Insertion time was 12.9 +/- 9.3 seconds in the warm group and 14.5 +/- 12.3
      seconds in the control group. Number of attempt for insertion was 1 in 77 cases,
      2 in 4 cases, and 3 in 1 case in the warm group and 1 in 79 cases and 2 in 7
      cases in the control group. Inspiratory pressure, leak pressure, and leak volume
      were not significantly different between the 2 groups, whereas leak volume had a
      tendency to be smaller in the warm group. CONCLUSION: Prewarming the I-gel to
      body temperature did not have any significant benefits in comparison with the I
      gel kept at room temperature.

PMID- 22626814
TI  - Predictors of bacteremia in emergency department patients with suspected
      infection.
AB  - OBJECTIVES: The goal of this study is to identify clinical variables associated
      with bacteremia. Such data could provide a rational basis for blood culture
      testing in emergency department (ED) patients with suspected infection. METHODS:
      This is a secondary analysis of a prospective cohort of ED patients with
      suspected infection. Data collected included demographics, vital signs, medical
      history, suspected source of infection, laboratory and blood culture results and
      outcomes. Bacteremia was defined as a positive blood culture by Centers for
      Disease Control criteria. Clinical variables associated with bacteremia on
      univariate logistic regression were entered into a multivariable model. RESULTS:
      There were 5630 patients enrolled with an average age of 59.9 +/- 19.9 years, and
      54% were female. Blood cultures were obtained on 3310 (58.8%). There were 409
      (12.4%) positive blood cultures, of which 68 (16.6%) were methicillin-resistant
      Staphylococcus aureus (MRSA) and 161 (39.4%) were Gram negatives. Ten covariates
      (respiratory failure, vasopressor use, neutrophilia, bandemia, thrombocytopenia,
      indwelling venous catheter, abnormal temperature, suspected line or urinary
      infection, or endocarditis) were associated with all-cause bacteremia in the
      final model (c-statistic area under the curve [AUC], 0.71). Additional factors
      associated with MRSA bacteremia included end-stage renal disease (odds ratio
      [OR], 3.9; 95% confidence interval [CI], 1.9-7.8) and diabetes (OR, 2.0; 95% CI,
      1.1-3.6) (AUC, 0.73). Factors strongly associated with Gram-negative bacteremia
      included vasopressor use in the ED (OR, 2.8; 95% CI, 1.7-4.6), bandemia (OR, 3.5;
      95% CI, 2.3-5.3), and suspected urinary infection (OR, 4.0; 95% CI, 2.8-5.8)
      (AUC, 0.75). CONCLUSIONS: This study identified several clinical factors
      associated with bacteremia as well as MRSA and Gram-negative subtypes, but the
      magnitude of their associations is limited. Combining these covariates into a
      multivariable model moderately increases their predictive value.

PMID- 22626815
TI  - Noninvasive pulse CO-oximetry expedites evaluation and management of patients
      with carbon monoxide poisoning.
AB  - PURPOSES: Pulse CO-oximetry (Rad-57; Masimo Corp, Irvine, CA) has been available
      since 2005. To date, all published clinical studies have focused on clinical
      reliability and whether the device enhances case finding through screening of
      various populations. This study examines whether use of pulse CO-oximetry
      shortens the time to diagnosis and treatment of patients with carbon monoxide
      (CO) poisoning. BASIC PROCEDURES: Data from the joint Undersea and Hyperbaric
      Medical Society/Centers for Disease Control and Prevention CO poisoning
      surveillance system from August 2008 to July 2011 were analyzed. Of 1711 cases of
      CO poisoning treated with hyperbaric oxygen in the United States and reported
      through the system, 1606 had their initial carboxyhemoglobin (COHb) level
      measured by laboratory CO-oximetry and 105 by pulse CO-oximetry. Patients were
      selected from the laboratory CO-oximetry group to match each of the 105 patients
      evaluated by pulse CO-oximetry in 5 characteristics--age, sex, race/ethnicity,
      intent of poisoning, and occurrence of loss of consciousness. Measures of
      timeliness in measurement and management were compared between the 2 groups. MAIN
      FINDINGS: Patients with initial COHb measurement by pulse CO-oximetry had
      significantly shorter time to measurement of COHb, higher average levels of COHb,
      and shorter time from the end of CO exposure to the initiation of hyperbaric
      oxygen treatment. On average, patients evaluated by pulse CO-oximetry reached the
      hyperbaric chamber 1 hour faster than did patients evaluated by laboratory CO
      oximetry (P < .01). PRINCIPLE CONCLUSIONS: Pulse CO-oximetry is associated with
      more rapid diagnosis and initiation of hyperbaric oxygen therapy in CO-poisoned
      patients compared with laboratory CO-oximetry. The impact on clinical outcome
      remains to be determined.

PMID- 22626816
TI  - Improving risk stratification in patients with chest pain: the Erlanger HEARTS3
      score.
AB  - BACKGROUND: The HEART score uses elements from patient History,
      Electrocardiogram, Age, Risk Factors, and Troponin to obtain a risk score on a 0-
      to 10-point scale for predicting acute coronary syndromes (ACS). This
      investigation seeks to improve on the HEART score by proposing the HEARTS(3)
      score, which uses likelihood ratio analysis to give appropriate weight to the
      individual elements of the HEART score as well as incorporating 3 additional "S"
      variables: Sex, Serial 2-hour electrocardiogram, and Serial 2-hour delta troponin
      during the initial emergency department valuation. METHODS: This is a
      retrospective analysis of a prospectively acquired database consisting of 2148
      consecutive patients with non-ST-segment elevation chest pain. Interval analysis
      of likelihood ratios was performed to determine appropriate weighting of the
      individual elements of the HEART(3) score. Primary outcomes were 30-day ACS and
      myocardial infarction. RESULTS: There were 315 patients with 30-day ACS and 1833
      patients without ACS. Likelihood ratio analysis revealed significant
      discrepancies in weight of the 5 individual elements shared by the HEART and
      HEARTS(3) score. The HEARTS(3) score outperformed the HEART score as determined
      by comparison of areas under the receiver operating characteristic curve for
      myocardial infarction (0.958 vs 0.825; 95% confidence interval difference in
      areas, 0.105-0.161) and for 30-day ACS (0.901 vs 0.813; 95% confidence interval
      difference in areas, 0.064-0.110). CONCLUSION: The HEARTS(3) score reliably risk
      stratifies patients with chest pain for 30-day ACS. Prospective studies need to
      be performed to determine if implementation of this score as a decision support
      tool can guide treatment and disposition decisions in the management of patients
      with chest pain.

PMID- 22626817
TI  - [Incidence and clinical impact of seizures after surgery for chronic subdural
      haematoma].
AB  - BACKGROUND AND PURPOSE: Seizures can occur in patients who have surgery for a
      chronic subdural hematoma. However, the incidence of seizures and their impact on
      the clinical course of patients in the perioperative period is not well known.
      METHODS: In this retrospective study, we reviewed 161 cases of patients treated
      for chronic subdural hematoma in our institution. The surgical procedures
      consisted in trephine craniotomy in 156 cases, burr-hole craniotomy in three
      cases, and bone flap craniotomy in two cases. All the patients had systematic
      antiepileptic drug prophylaxis. RESULTS: In our patients' population, the
      incidence of seizures was 10.6% before surgery and 14.9% after surgery. Low
      initial score on the Glasgow Coma Scale (P<0.001) and preoperative cognitive
      impairment (P=0.005) were associated with a higher rate of postoperative
      seizures. In our study, the mortality rate was 14.9%. Low initial score on the
      Glasgow Coma Scale (P=0.068) and postoperative seizures (P=0.002) were associated
      with a higher mortality rate. CONCLUSIONS: We have shown that patients suffering
      from seizures may have worse outcome. The benefit of a systematic perioperative
      prophylaxis using antiepileptic drugs has to be evaluated.

PMID- 22626818
TI  - Recent peritonitis associates with mortality among patients treated with
      peritoneal dialysis.
AB  - Peritonitis is a major complication of peritoneal dialysis, but the relationship
      between peritonitis and mortality among these patients is not well understood. In
      this case-crossover study, we included the 1316 patients who received peritoneal
      dialysis in Australia and New Zealand from May 2004 through December 2009 and
      either died on peritoneal dialysis or within 30 days of transfer to hemodialysis.
      Each patient served as his or her own control. The mean age was 70 years, and the
      mean time receiving peritoneal dialysis was 3 years. In total, there were 1446
      reported episodes of peritonitis with 27% of patients having >= 2 episodes.
      Compared with the rest of the year, there were significantly increased odds of
      peritonitis during the 120 days before death, although the magnitude of this
      association was much greater during the 30 days before death. Compared with a 30
      day window 6 months before death, the odds for peritonitis was six-fold higher
      during the 30 days immediately before death (odds ratio, 6.2; 95% confidence
      interval, 4.4-8.7). In conclusion, peritonitis significantly associates with
      mortality in peritoneal dialysis patients. The increased odds extend up to 120
      days after an episode of peritonitis but the magnitude is greater during the
      initial 30 days.

PMID- 22626819
TI  - Obesity and oxidative stress predict AKI after cardiac surgery.
AB  - Obesity increases oxidative stress, endothelial dysfunction, and inflammation,
      but the effect of obesity on postoperative AKI is not known. We examined the
      relationship between body mass index (BMI) and AKI in 445 patients undergoing
      cardiac surgery and whether oxidative stress (F(2)-isoprostanes), inflammation
      (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1])
      contribute to any identified relationship. Overall, 112 (25%) of the 445 patients
      developed AKI. Higher BMI was independently associated with increased odds of AKI
      (26.5% increase per 5 kg/m(2) [95% confidence interval, 4.3%-53.4%]; P=0.02).
      Baseline F(2)-isoprostane (P=0.04), intraoperative F(2)-isoprostane (P=0.003),
      and intraoperative PAI-1 (P=0.04) concentrations also independently predicted
      AKI. BMI no longer predicted AKI after adjustment for the effect of F(2)
      isoprostanes, suggesting that obesity may affect AKI via effects on oxidative
      stress. In contrast, adjustment for IL-6 or PAI-1 did not substantially alter the
      association between BMI and AKI. Further, deconstruction of the obesity-AKI
      relationship into direct (i.e., independent of candidate pathways) and indirect
      (i.e., effect of BMI on AKI via each candidate pathway) effects indicated that
      F(2)-isoprostanes, but not IL-6 or PAI-1, partially mediate the relationship
      between obesity and AKI (P=0.001). In conclusion, obesity independently predicts
      AKI after cardiac surgery, and oxidative stress may partially mediate this
      association.

PMID- 22626820
TI  - A hybrid CFHR3-1 gene causes familial C3 glomerulopathy.
AB  - Controlled activation of the complement system, a key component of innate
      immunity, enables destruction of pathogens with minimal damage to host tissue.
      Complement factor H (CFH), which inhibits complement activation, and five CFH
      related proteins (CFHR1-5) compose a family of structurally related molecules.
      Combined deletion of CFHR3 and CFHR1 is common and confers a protective effect in
      IgA nephropathy. Here, we report an autosomal dominant complement-mediated GN
      associated with abnormal increases in copy number across the CFHR3 and CFHR1
      loci. In addition to normal copies of these genes, affected individuals carry a
      unique hybrid CFHR3-1 gene. In addition to identifying an association between
      these genetic observations and complement-mediated kidney disease, these results
      provide insight into the protective role of the combined deletion of CFHR3 and
      CFHR1 in IgA nephropathy.

PMID- 22626822
TI  - The challenge of hyponatremia.
AB  - Treatment of hypotonic hyponatremia often challenges clinicians on many counts.
      Despite similar serum sodium concentrations, clinical manifestations can range
      from mild to life threatening. Some patients require active management, whereas
      others recover without intervention. Therapeutic measures frequently yield safe
      correction, yet the same measures can result in osmotic demyelination. To address
      this challenge, we present a practical approach to managing hyponatremia that
      centers on two elements: a diagnostic evaluation directed at the pathogenesis and
      putative causes of hyponatremia, the case-specific clinical and laboratory
      features, and the associated clinical risk; and a management plan tailored to the
      diagnostic findings that incorporates quantitative projections of fluid therapy
      and fluid losses on the patient's serum sodium, balances potential benefits and
      risks, and emphasizes vigilant monitoring. These principles should enable the
      clinician to formulate a management plan that addresses expeditiously three
      critical questions: Which of the determinants of the serum sodium are deranged
      and what is the underlying culprit? How urgent is the need for intervention? What
      specific therapy should be instituted and which are the associated pitfalls?

PMID- 22626823
TI  - Ranging behaviour of little bustard males, Tetrax tetrax, in the lekking grounds.
AB  - We investigated the ranging behaviour during the breeding season of 18
      radiotracked little bustard (Tetrax tetrax) males, a disperse-lekking species
      inhabiting the cereal pseudo-steppes. The average kernel 95% home range was 60+/
      50 ha and the average cluster 85% area was 17+/-17 ha. Range structure was as
      relevant as home range size for explaining the variation in the ranging behaviour
      of males, which could be partially explained by age, habitat quality and site.
      Ranging behaviour varied from males defending small and concentrated home ranges
      with high habitat quality, to males holding larger home ranges composed by
      several arenas. Our results suggest that social dominance and resource
      availability may affect ranging behaviour of males during the breeding season.
      Also, mating systems constraints may play a role on the use of space of males
      within the lekking ground. The ranging behaviour of a given male may be
      determined by a tendency to reduce and concentrate the home range as age and
      social status increase, and several fine-tuning mechanisms adjusting the ranging
      behaviour to the prevailing environmental or social factors on a given site and
      year.

PMID- 22626821
TI  - Normal and pathologic concentrations of uremic toxins.
AB  - An updated review of the existing knowledge regarding uremic toxins facilitates
      the design of experimental studies. We performed a literature search and found
      621 articles about uremic toxicity published after a 2003 review of this topic.
      Eighty-seven records provided serum or blood measurements of one or more solutes
      in patients with CKD. These records described 32 previously known uremic toxins
      and 56 newly reported solutes. The articles most frequently reported
      concentrations of beta2-microglobulin, indoxyl sulfate, homocysteine, uric acid,
      and parathyroid hormone. We found most solutes (59%) in only one report. Compared
      with previous results, more recent articles reported higher uremic concentrations
      of many solutes, including carboxymethyllysine, cystatin C, and parathyroid
      hormone. However, five solutes had uremic concentrations less than 10% of the
      originally reported values. Furthermore, the uremic concentrations of four
      solutes did not exceed their respective normal concentrations, although they had
      been previously described as uremic retention solutes. In summary, this review
      extends the classification of uremic retention solutes and their normal and
      uremic concentrations, and it should aid the design of experiments to study the
      biologic effects of these solutes in CKD.

PMID- 22626824
TI  - Evaluation of RapidChek Select for the screening of Salmonella in meat and meat
      products.
AB  - The efficacy of the RapidChek Select, an alternative rapid method based on
      lateral flow technology, for the screening of Salmonella in meat and meat
      products, was compared with the current ISO reference culture-based method. Of
      the 265 routine samples examined, 61 were found to be positive for Salmonella by
      both methods. The percentage of agreement between the results of two methods was
      determined as 98%. All presumptive positive results obtained by the RapidCheck
      Select were confirmed to be positive by ISO method. For five samples ISO method
      gave positive result, while RapidChek Select gave negative result. The limit of
      detection (LOD(50)) of RapidChek Select and ISO methods for minced beef meat
      samples were 1.00 cfu/25 g and 0.63 cfu/25 g, respectively. For sausage samples,
      LOD(50) of both methods were 2.00 cfu/25 g. As a result, the high agreement
      between two methods and the comparable detection limits of two methods showed
      that the RapidChek Select is an efficient alternative method for the screening of
      Salmonella in meat and meat products.

PMID- 22626825
TI  - Implication of bony cochlear nerve canal on hearing in patients with congenital
      unilateral sensorineural hearing loss.
AB  - This study was designed to evaluate the dimensions of the bony cochlear nerve
      canal (BCNC) in congenital unilateral sensorineural hearing loss (USNHL) patients
      with normal inner ears, and to analyze the correlation between BCNC and hearing
      status. Medical records and temporal bone computed tomography (TBCT) findings of
      380 patients who visited Seoul National University Hospital between January 1999
      and December 2007 were reviewed retrospectively. The length and width of the BCNC
      at the fundus of the internal auditory canal were measured in millimeters based
      on the axial view of TBCT for three ear groups: normal inner ears of control
      group subjects (group A, 179 ears), normal inner ears on the contralateral side
      of USNHL patients (group B, 201 ears), and the affected inner ears in USNHL
      (group C, 201 ears). The mean values of length and width in group C (0.79 +/-
      0.36 and 1.58 +/- 0.83 mm, respectively) were significantly smaller than those in
      group A (1.07 +/- 0.10 and 2.38 +/- 0.28 mm, respectively; p < 0.001) and group B
      (1.04 +/- 0.23 and 2.33 +/- 0.39 mm, respectively; p < 0.001). The receiver
      operating characteristic curves for BCNC were conducted to estimate the cutoff
      values from which the proportions of profound hearing loss increased, compared to
      those of mild to severe hearing loss. The areas under the curve were 0.487 +/-
      0.044 (p = 0.781) and 0.622 +/- 0.041 (p = 0.011) for length and width,
      respectively. The cutoff value of width with a sensitivity of 90% for profound
      USNHL was 1.16 mm in otherwise normal inner ears. Clinicians would be recommended
      to take a close look at BCNC as one of the possible causes of hearing loss in
      otherwise normal inner ears of USNHL on TBCT.

PMID- 22626826
TI  - Bi-enzyme L-arginine-selective amperometric biosensor based on ammonium-sensing
      polyaniline-modified electrode.
AB  - A novel L-arginine-selective amperometric bi-enzyme biosensor based on
      recombinant human arginase I isolated from the gene-engineered strain of
      methylotrophic yeast Hansenula polymorpha and commercial urease is described. The
      biosensing layer was placed onto a polyaniline-Nafion composite platinum
      electrode and covered with a calcium alginate gel. The developed sensor revealed
      a good selectivity to L-arginine. The sensitivity of the biosensor was 110 +/-
      1.3 nA/(mM mm(2)) with the apparent Michaelis-Menten constant (K(M)(app)) derived
      from an L-arginine (L-Arg) calibration curve of 1.27 +/- 0.29 mM. A linear
      concentration range was observed from 0.07 to 0.6mM, a limit of detection being
      0.038 mM and a response time - 10s. The developed biosensor demonstrated good
      storage stability. A laboratory prototype of the proposed amperometric biosensor
      was applied to the samples of three commercial pharmaceuticals ("Tivortin",
      "Cytrarginine", "Aminoplazmal 10% E") for L-Arg testing. The obtained L-Arg
      content values correlated well with those declared by producers.

PMID- 22626827
TI  - Electrochemical detection of individual single nucleotide polymorphisms using
      monobase-modified apoferritin-encapsulated nanoparticles.
AB  - An electrochemical approach for detection of individual single nucleotide
      polymorphisms (SNPs) based on nucleobase-conjugated apoferritin probe loaded with
      metal phosphate nanoparticles is reported. Coupling of the nucleotide-modified
      nanoparticle probe to the mutant sites of duplex DNA was induced by DNA
      polymerase I (Klenow fragment) to preserve Watson-Crick base-pairing rules. After
      sequential liquid hybridization of biotinylated DNA probes with mutant DNA and
      complementary DNA, the resulting duplex DNA helixes were captured to the surface
      of magnetic beads through a well known and specific biotin-streptavidin affinity
      binding. For signaling each of eight possible Single-nucleotide polymorphisms
      (SNPs), Pb, Cu, Cd and Zn phosphate-loaded apoferritin nanoparticle probes were
      linked to adenosine (A), cytidine (C), guanosine (G), and thymidine (T)
      mononucleotides, respectively. Monobase-conjugated apoferritin probes were
      coupled to the mutant sites of the formed duplex DNA in the presence of DNA
      polymerase. Electrochemical stripping analyses of the metals loaded in
      apoferritin nanoparticle probes provide a means for detection and quantification
      of mutant DNA. Each mutation captures different nucleotide-conjugated apoferritin
      probe and provide a distinct four-potential voltammogram, whose peak potentials
      reflect the identity of the mismatch. The method is sensitive enough to
      accurately determine AG mutation, as the most thermodynamically stable mismatch
      to detect, in the range of 50-600 pM. The proposed protocol provides a simple,
      fast, cost-effective, accurate and sensitive method for detection of SNPs.

PMID- 22626828
TI  - Aptamer-conjugated silver nanoparticles for electrochemical detection of
      adenosine triphosphate.
AB  - The capability of silver nanoparticles (SNP) as redox tag in the construction of
      an electrochemical aptasensor for the detection of adenosine triphosphate (ATP)
      is investigated in the present manuscript. To construct the aptasensor, a well
      known ATP binding aptamer (ABA) splits into two segments. The first amino-labeled
      segment of the aptamer was covalently immobilized on 3-mercaptopropionic acid
      modified gold electrode surface by the formation of carbodiimide bond. The second
      segment was modified by SNPs and associated with the first segment in the
      presence of ATP. The direct oxidation signal of SNPs is followed as the
      analytical signal to detect ATP. The sandwich assay shows a suitable signal gain
      and importantly, a good response time. The sensor can detect the concentrations
      of ATP as low as micromolar scales with a desirable stability under optimum
      conditions. Furthermore, analog nucleotides including GTP, UTP and CTP, do not
      show serious interferences and this sensor readily detects its target in a
      complex media such as human blood plasma.

PMID- 22626829
TI  - Amplified surface plasmon resonance immunosensor for interferon-gamma based on a
      streptavidin-incorporated aptamer.
AB  - Interferon-gamma (IFN-gamma) is associated with susceptibility to tuberculosis,
      which is a major public health problem worldwide. Although significant progress
      has been made with regard to the design of enzyme immunoassays for IFN-gamma,
      this assay is still labor-intensive and time-consuming. We therefore designed a
      DNA aptamer hairpin structure for the detection of IFN-gamma with high
      sensitivity and selectivity. A streptavidin DNA aptamer was incorporated into the
      IFN-gamma binding aptamer probe for the amplified detection of the target
      molecules. Initially, the probe remained in the inactive configuration. The
      addition of IFN-gamma induced the rearrangement of the aptamer structure,
      allowing the self-assembly of the active streptavidin aptamer conformation for
      the streptavidin molecular recognition. Under optimized conditions, the detection
      limit was determined to be 33 pM, with a dynamic range from 0.3 to 333 nM, both
      of which were superior to those of corresponding optical sensors. Because
      combined aptamers are composed of nucleic acids, this optical aptasensor provided
      the advantages of high sensitivity, simplicity, reusability, and no further
      labeling or sample pre-treatment.

PMID- 22626830
TI  - Highly sensitive and selective photoelectrochemical DNA sensor for the detection
      of Hg2+ in aqueous solutions.
AB  - A "turn-on" photoelectrochemical sensor for Hg(2+) detection based on thymine
      Hg(2+)-thymine interaction is presented by using a thymine-rich oligonucleotide
      film and a double-strand DNA intercalator, Ru(bpy)(2)(dppz)(2+) (bpy=2,2'
      bipyridine, dppz=dipyrido[3,2-a:2',3'-c]phenazine) as the photocurrent signal
      reporter. The presence of Hg(2+) induces the formation of a double helical DNA
      structure which provides binding sites for Ru(bpy)(2)(dppz)(2+). The double
      helical structure was confirmed by circular dichroism and fluorescence
      measurements. Under the optimized conditions, a linear relationship between
      photocurrent and Hg(2+) concentration was obtained over the range of 0.1 nM to 10
      nM Hg(2+), with a detection limit of 20 pM. Interference by 10 other metal ions
      was negligible. Analytical results of Hg(2+) spiked into tap water and lake water
      by the sensor were in good agreement with mass spectrometry data. With the
      advantages of high sensitivity and selectivity, simple sensor construction, low
      instrument cost and low sample volume, this method is potentially suitable for
      the on-site monitoring of Hg(2+) contamination.

PMID- 22626831
TI  - New strategies for detecting steroid metabolic disorders--paneling vs profiling.

PMID- 22626832
TI  - Citrullinated mouse collagen administered to DBA/1J mice in the absence of
      adjuvant initiates arthritis.
AB  - INTRODUCTION: Citrullinated self-proteins are thought to be involved in the
      onset/progression of rheumatoid arthritis (RA). Numerous studies have been
      performed to look for the self-antigen that becomes citrullinated and induces RA.
      Importantly, these studies have been performed using citrullinated self-antigens
      injected into an animal model in the presence of a strong adjuvant in order to
      derive the response. However, to date no studies have been performed to determine
      if these phenotypes can be induced in the absence of an adjuvant. METHODS: To
      investigate this possibility, mice were immunized with citrullinated or non
      citrullinated mouse Type II collagen (Cit-Col or Col) in the presence or absence
      of Freund's Complete Adjuvant (FCA). RESULTS: An autoimmune-like RA response was
      observed in mice immunized with Cit-Col in the absence of FCA; by the increase in
      caliper score, visual observation, and micro-CT analysis of bone erosions.
      Antibody and T-cell responses were increased in the Cit-Col injected mice to Cit
      Col as well as antibody to Anti-Citrullinated Peptide Antigens (ACPA) as
      determined by a commercially available test kit. CONCLUSIONS: Therefore, the use
      of citrullinated mouse collagen induces an autoimmune-like RA in the absence of
      an adjuvant. These data also suggest that citrullinate self-proteins may be
      potential molecular adjuvants that assist in driving an inflammatory response,
      that increases the production of PAD in joint tissue, resulting in the
      citrullination of other self-proteins to exacerbate the disease.

PMID- 22626833
TI  - A finite-element approach to the direct computation of relative cardiovascular
      pressure from time-resolved MR velocity data.
AB  - The evaluation of cardiovascular velocities, their changes through the cardiac
      cycle and the consequent pressure gradients has the capacity to improve
      understanding of subject-specific blood flow in relation to adjacent soft tissue
      movements. Magnetic resonance time-resolved 3D phase contrast velocity
      acquisitions (4D flow) represent an emerging technology capable of measuring the
      cyclic changes of large scale, multi-directional, subject-specific blood flow. A
      subsequent evaluation of pressure differences in enclosed vascular compartments
      is a further step which is currently not directly available from such data. The
      focus of this work is to address this deficiency through the development of a
      novel simulation workflow for the direct computation of relative cardiovascular
      pressure fields. Input information is provided by enhanced 4D flow data and
      derived MR domain masking. The underlying methodology shows numerical advantages
      in terms of robustness, global domain composition, the isolation of local fluid
      compartments and a treatment of boundary conditions. This approach is
      demonstrated across a range of validation examples which are compared with
      analytic solutions. Four subject-specific test cases are subsequently run,
      showing good agreement with previously published calculations of intra-vascular
      pressure differences. The computational engine presented in this work contributes
      to non-invasive access to relative pressure fields, incorporates the effects of
      both blood flow acceleration and viscous dissipation, and enables enhanced
      evaluation of cardiovascular blood flow.

PMID- 22626834
TI  - The nature of cardiac calcification in aortic stenosis.

PMID- 22626835
TI  - Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium
      and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind
      placebo-controlled trial among elderly Swedish citizens.
AB  - BACKGROUND: Selenium and coenzyme Q10 are essential for the cell. Low cardiac
      contents of selenium and coenzyme Q10 have been shown in patients with
      cardiomyopathy, but inconsistent results are published on the effect of
      supplementation of the two components separately. A vital relationship exists
      between the two substances to obtain optimal function of the cell. However,
      reports on combined supplements are lacking. METHODS: A 5-year prospective
      randomized double-blind placebo-controlled trial among Swedish citizens aged 70
      to 88 was performed in 443 participants given combined supplementation of
      selenium and coenzyme Q10 or a placebo. Clinical examinations, echocardiography
      and biomarker measurements were performed. Participants were monitored every 6th
      month throughout the intervention. The cardiac biomarker N-terminal proBNP (NT
      proBNP) and echocardiographic changes were monitored and mortalities were
      registered. End-points of mortality were evaluated by Kaplan-Meier plots and Cox
      proportional hazard ratios were adjusted for potential confounding factors.
      Intention-to-treat and per-protocol analyses were applied. RESULTS: During a
      follow up time of 5.2 years a significant reduction of cardiovascular mortality
      was found in the active treatment group vs. the placebo group (5.9% vs. 12.6%;
      P=0.015). NT-proBNP levels were significantly lower in the active group compared
      with the placebo group (mean values: 214 ng/L vs. 302 ng/L at 48 months;
      P=0.014). In echocardiography a significant better cardiac function score was
      found in the active supplementation compared to the placebo group (P=0.03).
      CONCLUSION: Long-term supplementation of selenium/coenzyme Q10 reduces
      cardiovascular mortality. The positive effects could also be seen in NT-proBNP
      levels and on echocardiography.

PMID- 22626837
TI  - Recurrent right ventricular echinococcosis characterized by cardiac magnetic
      resonance.

PMID- 22626836
TI  - Trends in prevalence, awareness, treatment, and control of hypertension among
      Chinese adults 1991-2009.

PMID- 22626838
TI  - Impact of high post-loading platelet aggregation on 30-day clinical outcomes
      after primary percutaneous coronary intervention. The antiplatelet regimen
      tailoring after primary PCI (ART-PCI) trial.
AB  - BACKGROUND: Patients with high post-loading platelet aggregation (PPA) are at
      increased risk of stent thrombosis and death after primary percutaneous coronary
      intervention (pPCI). The objective of the present trial was to examine whether
      high PPA is associated with adverse clinical outcomes in pPCI patients whose
      therapy was modified in accordance with PPA. METHODS: We analyzed 961 consecutive
      pPCI patients who underwent pPCI between February 2008 and June 2011. High PPA
      was defined as PPA >50%, 24h after the loading dose. Patients with high PPA were
      treated with aspirin 300 mg, clopidogrel 150 mg or ticlopidine 500 mg for 30
      days. The co-primary efficacy and safety end points at 30 days were major adverse
      cardiovascular events (MACE) and major bleeding. RESULTS: We detected high PPA to
      clopidogrel and aspirin in 44.4% and 16.5% of patients, respectively. The rates
      of 30-day MACE (adjusted OR 1.76, 95% CI 1.05-2.97), definite subacute stent
      thrombosis (DSST, adjusted OR 2.15, 95% CI 1.09-4.22) and nonfatal infarction
      (adjusted OR 3.99, 95% CI 1.57-10.13) were higher in patients with high PPA to
      clopidogrel compared with responders. High PPA to aspirin was not associated with
      an adverse 30-day clinical outcome. Compared with high PPA patients who were not
      tailored, a significantly better outcome with respect to the primary end point
      was observed in the tailored group (OR 0.42, 95% CI 0.19-0.93). CONCLUSION: High
      PPA to clopidogrel was an independent predictor of 30-day adverse events after
      pPCI. Among high PPA patients, tailoring was associated with an improved primary
      outcome.

PMID- 22626839
TI  - Are treatments for vasovagal syncope effective? A meta-analysis.
AB  - BACKGROUND: Therapies used to treat vaso-vagal syncope (VVS) recurrence have not
      been proven effective in single studies. METHODS: Comprehensive search of PubMed,
      EMBASE and Cochrane Central databases of published trials was done. Randomized or
      non-randomized studies, comparing the intervention of interest to control
      group(s), with the endpoint of spontaneous recurrence or syncope on head-up tilt
      test, were included. Data were extracted on an intention-to-treat basis. Study
      heterogeneity was analyzed by Cochran's Q statistics. A random-effect analysis
      was used. RESULTS: alpha-adrenergic agonists were found effective (n=400, OR
      0.19, CI 0.06-0.62, p<0.05) in preventing VVS recurrence. beta-blockers were not
      found to be effective when only randomized studies comparing beta-blockers to non
      pharmacologic agents were assessed (9 studies, n=583, OR 0.48, CI 0.22-1.04,
      p=0.06). Tilt-training had no effect when only randomized studies were considered
      (4 studies, n=298, OR 0.47, CI 0.21-1.05, p=0.07). Selective serotonin reuptake
      inhibitors were found effective (n=131, OR 0.28, CI 0.10-0.74, p<0.05), though
      the analysis contained only 2 studies. Pacemakers were found effective in
      preventing syncope recurrence when all studies were analyzed (n=463, OR 0.13, CI
      0.05-0.36, p<0.05). However, studies comparing active pacemaker to sensing mode
      only did not show benefit (3 studies, n=162, OR 0.45, CI 0.09-2.14, p=0.32).
      CONCLUSIONS: This meta-analysis highlights the totality of evidence for commonly
      used medications used to treat VVS, and the requirement for larger, double-blind,
      placebo controlled trials with longer follow-up.

PMID- 22626840
TI  - Which are the most reliable predictors of recurrence of atrial fibrillation after
      transcatheter ablation?: a meta-analysis.
AB  - CONTEXT: Transcatheter ablation of atrial fibrillation (AF) has undergone
      important development, with acceptable midterm results in terms of the safety and
      recurrence. A meta-analysis was performed to identify the periprocedural
      complications, midterm success rates and predictors of recurrence after AF
      ablation. METHODS AND RESULTS: 4357 patients with paroxysmal AF, 1083 with
      persistent AF and 1777 with long standing AF were included. The pooled analysis
      showed that there was an in-hospital complication rate of tamponade requiring
      drainage of 0.99% (0.44-1.54; CI 99%), stroke with neurological persistent
      impairment of 0.22% (0.04-0.47; CI 99%), and stroke without of 0.36% (0.03-0.70;
      CI 99%) After a follow up of 22 (13-28) months and 1.23 (1.19-1.5; CI 99%)
      procedures per patient, the AF recurrence rate was 31.20% (24.87-34.81; CI 99%).
      The persistent AF patients exhibited a greater risk of recurrence after the first
      ablation (OR 1.78 [1.14, 2.77] CI 99%), but a trend towards non significance was
      present in the patients with more than one procedure (OR 1.69 [0.95, 3.00] CI
      99%). The most powerful predictors of an AF ablation failure in the overall
      population were a recurrence within 30-days (OR 4.30; 2.00-10.80), valvular AF
      (OR 5.20; 2.22-9.50) and a left atrium diameter of more than 50mm (OR 5.10 2.00
      12.90; all CI 95%). CONCLUSIONS: Persistent AF remains burdened from higher
      recurrence rates, however not so following redo-procedures. Three predictors,
      valvular AF, a left atrium diameter longer than 50mm and recurrence within 30
      days, could be appraised to drive selection of patients and therapeutic strategy.

PMID- 22626841
TI  - Impact of a cardiac rehabilitation program and inflammatory state on endothelial
      progenitor cells in acute coronary syndrome patients.
AB  - BACKGROUND: Among the benefits of a cardiac rehabilitation (CR) program for
      patients after an acute coronary syndrome (ACS) is the mobilization of
      endothelial progenitor cells (EPCs). However not all patients respond to CR with
      an increase of EPC. We performed this study to identify the characteristics of
      patients who will not benefit from an increase of EPCs at the end of a CR
      program. METHODS: 112 ACS patients were admitted to a four-week CR program. EPCs,
      high sensitivity C-reactive protein (hsCRP) and NT-ProBNP levels were determined
      at the beginning (T1) and at the end (T2) of the CR program. All patients
      performed a cardiopulmonary exercise test at T1 and at T2. EPCs were defined as
      CD34+KDR+, CD133+KDR+ and CD34+CD133+KDR+. hsCRP and NT-ProBNP were measured by
      nephelometric and immunometric method, respectively. RESULTS: At T2, we observed
      a significant increase of EPCs (p=0.001), VO2 peak, Watt max HDL-cholesterol
      (p<0.0001) and a significant decrease (p<0.001) of hsCRP and NT-ProBNP,
      triglycerides, HbA1c, systolic blood pressure and waist circumference. Variations
      of VO2 peak were significantly correlated with the variations of EPCs. Patients
      with increased EPCs showed significantly (p=0.01) lower baseline levels of CRP
      and higher basal Watt max (p=0.04). In a multivariate logistic regression
      analysis, the lowest tertile of baseline hsCRP significantly affected the
      likelihood of having an increase of EPCs at the end of the CR program.
      CONCLUSIONS: A CR program determines an increase of EPCs with a decrease of CRP
      and NT-ProBNP. A different trend for EPCs can be detected among patients
      correlated to CRP levels and exercise tolerance.

PMID- 22626842
TI  - New antiviral therapies in the management of HCV infection.
AB  - Improved knowledge of the HCV life cycle and of structural features of HCV
      proteins have led to the discovery of numerous potential targets for antiviral
      therapy. Viral replication and polyprotein processing have been tagged as
      promising viral targets. Clathrin-mediated endocytosis, fusion of HCV with
      cellular membranes, translation of viral RNA, virus production and release as
      well as several host cell factors may provide alternative targets for future anti
      HCV therapies. Several compounds are currently under investigation in clinical
      trials and showed high antiviral activity in patients with chronic hepatitis C.
      Recently, Phase III studies for two protease inhibitors, telaprevir and
      boceprevir, each given in combination with pegylated interferon (standard of care
      [SOC]), were completed. In HCV-genotype-1-infected patients, the addition of
      telaprevir or boceprevir to SOC increased sustained virological response rates
      from <50% to >70%. Nucleoside/nucleotide inhibitors of the HCV NS5B polymerase
      have shown antiviral activity against different HCV genotypes, and have a higher
      barrier to resistance than protease inhibitors. In addition, several allosteric
      binding sites have been identified for non-nucleoside inhibitors of the NS5B
      polymerase. Inhibitors of NS5A are potentially active against all HCV genotypes.
      Among the different host cell-targeting compounds, cyclophilin inhibitors have
      shown promising results. Future hope lies in the combination of direct-acting
      antiviral agents with the possibility of interferon-free treatment regimens.

PMID- 22626844
TI  - Segregation of secondary metabolite biosynthesis in hybrids of Fusarium fujikuroi
      and Fusarium proliferatum.
AB  - Fusarium fujikuroi and Fusarium proliferatum are two phylogenetically closely
      related species of the Gibberella fujikuroi species complex (GFC). In some cases,
      strains of these species can cross and produce a few ascospores. In this study,
      we analyzed 26 single ascospore isolates of an interspecific cross between F.
      fujikuroi C1995 and F. proliferatum D4854 for their ability to produce four
      secondary metabolites: gibberellins (GAs), the mycotoxins fusarin C and fumonisin
      B(1), and a family of red polyketides, the fusarubins. Both parental strains
      contain the biosynthetic genes for all four metabolites, but differ in their
      ability to produce these metabolites under certain conditions. F. fujikuroi C1995
      produces GAs and fusarins, while F. proliferatum D4854 produces fumonisins and
      fusarubins. The segregation amongst the progeny of these traits is not the
      expected 1:1 Mendelian ratio. Only eight, six, three and three progeny,
      respectively, produce GAs, fusarins, fumonisin B(1) and fusarubins in amounts
      similar to those synthesized by the producing parental strain. Beside the eight
      highly GA(3)-producing progeny, some of the progeny produce small amounts of GAs,
      predominantly GA(1), although these strains contain the GA gene cluster of the
      non-GA-producing F. proliferatum parental strain. Some progeny had recombinant
      secondary metabolite profiles under the conditions examined indicating that
      interspecific crosses can yield secondary metabolite production profiles that are
      atypical of the parent species.

PMID- 22626843
TI  - Sex-specific gene expression during asexual development of Neurospora crassa.
AB  - The impact of loci that determine sexual identity upon the asexual, dominant
      stage of fungal life history has been well studied. To investigate their impact,
      expression differences between strains of different mating type during asexual
      development were assayed, with RNA sampled from otherwise largely isogenic mat A
      and mat a strains of Neurospora crassa at early, middle, and late clonal stages
      of development. We observed significant differences in overall gene expression
      between mating types across clonal development, especially at late development
      stages. The expression levels of mating-type genes and pheromone genes were
      assayed by reverse transcription and quantitative PCR, revealing expression of
      pheromone and receptor genes in strains of both mating types in all development
      stages, and revealing that mating type (mat) genes were increasingly expressed
      over the course of asexual development. Interestingly, among differentially
      expressed genes, the mat A genotype more frequently exhibited a higher expression
      level than mat a, and demonstrated greater transcriptional regulatory dynamism.
      Significant up-regulation of expression was observed for many late light
      responsive genes at late asexual development stages. Further investigation of the
      impact of light and the roles of light response genes in asexual development of
      both mating types are warranted.

PMID- 22626845
TI  - Concurrent JAK2(V617F) mutation and MTHFR(C677T) homozygosity in an adolescent
      with polycythemia vera: case report and discussion.

PMID- 22626846
TI  - Managing medical equipment used by technology-dependent children: evaluation of
      an instructional tool for pediatric residents and medical students.
AB  - OBJECTIVES: To evaluate the effectiveness of a workshop on managing medical
      devices used in technology-dependent children. METHODS: Study participants
      included residents and medical students rotating in the pediatrics department at
      the time of the study. A workshop was conducted consisting of learning stations
      for common medical devices, including brief presentations and opportunities for
      hands-on practice with each device. Participants completed surveys before and
      after the workshop assessing their perceived ability to manage medical equipment
      before and after the workshop and their ongoing learning needs. RESULTS: All
      participants indicated a substantial need for training on how to manage medical
      devices used by technology-dependent patients. Scores for perceived ability to
      manage the devices improved significantly after workshop participation for nearly
      all devices taught. CONCLUSIONS: Medical trainees have significant learning needs
      for managing devices used by technology-dependent patients. Hands-on, small-group
      training can be an effective instructional tool for improving confidence in these
      skills.

PMID- 22626848
TI  - A novel dual-site transcranial magnetic stimulation paradigm to probe fast
      facilitatory inputs from ipsilateral dorsal premotor cortex to primary motor
      cortex.
AB  - The dorsal premotor cortex (PMd) plays an import role in action control,
      sensorimotor integration and motor recovery. Animal studies and human data have
      demonstrated direct connections between ipsilateral PMd and primary motor cortex
      hand area (M1(HAND)). In this study we adopted a multimodal approach combining
      highly focal dual-site TMS (dsTMS) and diffusion tensor imaging (DTI) to probe
      ipsilateral effective and structural connectivity between PMd and M1(HAND) in
      humans. A suprathreshold test stimulus (TS) was applied to left M1(HAND)
      producing a motor evoked potential (MEP) and a subsequent conditioning stimulus
      (CS) to ipsilateral rostromedial PMd at short latencies ranging from of 0.8 to
      2.0 ms. At an interstimulus interval of 1.2 ms, dsTMS of the left M1(HAND) and
      PMd facilitated MEP amplitudes relative to unconditioned TMS of M1(HAND). This
      PMd to M1(HAND) facilitation was absent during voluntary contraction of the
      target muscle. During a two-choice reaction time task, PMd-M1(HAND) facilitation
      was only observed when dsTMS was given 125 ms after presentation of the cue and
      subjects responded with their right hand, but not for left hand responses. Our
      results reveal a short-latency PMd to M1(HAND) connection which modulates
      excitability of ipsilateral M1(HAND) in a task and effector specific manner. DTI
      revealed that individual increases in PMd to M1(HAND) facilitation were
      correlated with fractional anisotropy and axial diffusivity in the juxtacortical
      white matter underlying the caudal portion of the left superior frontal gyrus.
      This finding shows that the functional strength of this connection from medial
      PMd to M1(HAND) has a microstructural correlate in the underlying subcortical
      white matter. This novel dsTMS paradigm can be used to non-invasively probe
      effective PMd to M1(HAND) connectivity in healthy individuals and patients with
      impaired hand function.

PMID- 22626847
TI  - Arginylation regulates myofibrils to maintain heart function and prevent dilated
      cardiomyopathy.
AB  - Protein arginylation mediated by arginyltransferase (ATE1) is essential for heart
      formation during embryogenesis, however its cell-autonomous role in
      cardiomyocytes and the differentiated heart muscle has never been investigated.
      To address this question, we generated cardiac muscle-specific Ate1 knockout
      mice, in which Ate1 deletion was driven by alpha-myosin heavy chain promoter
      (alphaMHC-Ate1 mouse). These mice were initially viable, but developed severe
      cardiac contractility defects, dilated cardiomyopathy, and thrombosis over time,
      resulting in high rates of lethality after 6months of age. These symptoms were
      accompanied by severe ultrastructural defects in cardiac myofibrils, seen in the
      newborns and far preceding the onset of cardiomyopathy, suggesting that these
      defects were primary and likely underlay the development of the future heart
      defects. Several major sarcomeric proteins were arginylated in vivo. Moreover,
      Ate1 deletion in the hearts resulted in a significant reduction of active and
      passive myofibril forces, suggesting that arginylation is critical for both
      myofibril structural integrity and contractility. Thus, arginylation is essential
      for maintaining the heart function by regulation of the major myofibril proteins
      and myofibril forces, and its absence in the heart muscle leads to progressive
      heart failure through cardiomyocyte-specific defects.

PMID- 22626849
TI  - Assessment of fetal myocardial deformation using speckle tracking techniques.
AB  - OBJECTIVE: To report the current status of speckle tracking techniques in
      evaluation of fetal myocardial deformation. METHODS: A variety of non-Doppler
      ultrasound methods are available using offline analysis of standard four-chamber
      and short axis views of the heart. RESULTS: Most reports have used techniques
      developed for the measurement of strain and strain rate in the adult heart and
      produced conflicting descriptions of gestational changes in strain. Myocardial
      velocities usually reflect mean modal velocities and are lower than the peak
      velocities obtained using Doppler techniques. CONCLUSIONS: In the fetus, most
      current methods of acquisition result in frame rates that are too low, and the
      fetal heart size is too small to achieve reliable measures of fetal myocardial
      deformation.

PMID- 22626850
TI  - Methodology for agricultural and rural NPS pollution in a typical county of the
      North China Plain.
AB  - Agricultural non-point source (NPS) pollution has been recently identified by the
      Chinese government as a major source of aquatic pollution. Methodologies commonly
      used to make basin-wide or area-wide assessments are problematic and regional
      distinctions have not been made relative to rainfall and runoff. Using a typical
      agricultural county in the Hai River basin of the North China Plan we developed
      methodology to estimate potential load and delivered load for crops (field crops
      + rice), animal production, rural living and from atmospheric N input. We use
      scenarios to allow for uncertainty in delivery to estimate the relative roles of
      different rural forms of pollution. Livestock raising is the major source of NPS
      pollution. Despite a 75% rural population, rural living contributes almost
      nothing to surface water pollution. While over-fertilization is typical, nutrient
      runoff from crops is low. Our results have implications for policies now under
      development for NPS control in China.

PMID- 22626852
TI  - Early childhood environment and dementia.

PMID- 22626851
TI  - Dementia incidence and mortality in middle-income countries, and associations
      with indicators of cognitive reserve: a 10/66 Dementia Research Group population
      based cohort study.
AB  - BACKGROUND: Results of the few cohort studies from countries with low incomes or
      middle incomes suggest a lower incidence of dementia than in high-income
      countries. We assessed incidence of dementia according to criteria from the 10/66
      Dementia Research Group and Diagnostic and Statistical Manual of Mental Disorders
      (DSM) IV, the effect of dementia at baseline on mortality, and the independent
      effects of age, sex, socioeconomic position, and indicators of cognitive reserve.
      METHODS: We did a population-based cohort study of all people aged 65 years and
      older living in urban sites in Cuba, the Dominican Republic, and Venezuela, and
      rural and urban sites in Peru, Mexico, and China, with ascertainment of incident
      10/66 and DSM-IV dementia 3-5 years after cohort inception. We used
      questionnaires to obtain information about age in years, sex, educational level,
      literacy, occupational attainment, and number of household assets. We obtained
      information about mortality from all sites. For participants who had died, we
      interviewed a friend or relative to ascertain the likelihood that they had
      dementia before death. FINDINGS: 12,887 participants were interviewed at
      baseline. 11,718 were free of dementia, of whom 8137 (69%) were reinterviewed,
      contributing 34,718 person-years of follow-up. Incidence for 10/66 dementia
      varied between 18.2 and 30.4 per 1000 person-years, and were 1.4-2.7 times higher
      than were those for DSM-IV dementia (9.9-15.7 per 1000 person-years). Mortality
      hazards were 1.56-5.69 times higher in individuals with dementia at baseline than
      in those who were dementia-free. Informant reports suggested a high incidence of
      dementia before death; overall incidence might be 4-19% higher if these data were
      included. 10/66 dementia incidence was independently associated with increased
      age (HR 1.67; 95% CI 1.56-1.79), female sex (0.72; 0.61-0.84), and low education
      (0.89; 0.81-0.97), but not with occupational attainment (1.04; 0.95-1.13).
      INTERPRETATION: Our results provide supportive evidence for the cognitive reserve
      hypothesis, showing that in middle-income countries as in high-income countries,
      education, literacy, verbal fluency, and motor sequencing confer substantial
      protection against the onset of dementia. FUNDING: Wellcome Trust Health
      Consequences of Population Change Programme, WHO, US Alzheimer's Association,
      FONACIT/ CDCH/ UCV.

PMID- 22626853
TI  - Tuberous sclerosis: computed tomography diagnosis.

PMID- 22626854
TI  - Essays on citation classics in Developmental Neuroscience.

PMID- 22626855
TI  - Genistein enhances the effect of trichostatin A on inhibition of A549 cell growth
      by increasing expression of TNF receptor-1.
AB  - Our previous study has shown that genistein enhances apoptosis in A549 lung
      cancer cells induced by trichostatin A (TSA). The precise molecular mechanism
      underlying the effect of genistein, however, remains unclear. In the present
      study, we investigated whether genistein enhances the anti-cancer effect of TSA
      through up-regulation of TNF receptor-1 (TNFR-1) death receptor signaling. We
      incubated A549 cells with TSA (50 ng/mL) alone or in combination with genistein
      and then determined the mRNA and protein expression of TNFR-1 as well as the
      activation of downstream caspases. Genistein at 5 and 10 MUM significantly
      enhanced the TSA-induced decrease in cell number and apoptosis in a dose
      dependent manner. The combined treatment significantly increased mRNA and protein
      expression of TNFR-1 at 6 and 12h, respectively, compared with that of the
      control group; while TSA alone had no effect. TSA in combination with 10 MUM of
      genistein increased TNFR-1 mRNA and protein expression by about 70% and 40%,
      respectively. The underlying mechanism for this effect of genistein may be partly
      associated with the estrogen receptor pathway. The combined treatment also
      increased the activation of caspase-3 and -10 as well as p53 protein expression
      in A549 cells. The enhancing effects of genistein on the TSA-induced decrease in
      cell number and on the expression of caspase-3 in A549 cells were suppressed by
      silencing TNFR-1 expression. These data demonstrated that the upregulation of
      TNFR-1 death receptor signaling plays an important role, at least in part, in the
      enhancing effect of genistein on TSA-induced apoptosis in A549 cells.

PMID- 22626856
TI  - Early or delayed cholecystectomy (LC) for acute gallstone pancreatitis? An
      experience and review.
AB  - BACKGROUND/AIMS: The timing for the management of gallstones pancreatitis remains
      a contentious issue. Various scholars have their own achievement in in regards to
      this issue. METHODOLOGY: We reviewed our hospital charts from Jan 2007 to
      December 2010 and made a comparative study about early and delayed LC for mild to
      moderate gallstone pancreatitis in 80 patients. RESULTS: Successful management
      was obtained in all patients. Out of 80 patients, 54 had underwent for early LC
      within 48 hours and 26 delayed LC (6-8 weeks). CONCLUSIONS: Our study reveals
      that early cholecystectomy has nice outcomes in terms of shorter hospital stay
      and expenses. Proper consultation should be taken from radiological colleague if
      CBD dilations are >6 mm and contraction of gallbladder appears on imaging
      modalities. Comorbid conditions, past history of cholecystitis cannot be avoided
      for proper surgical outcomes. Postoperative complications can be deterred by
      early LC for mild gallstone pancreatitis. However, large volume studies are
      essential from different places to answer the debated topic of which management
      protocol is justifiable for the management of mild to moderate gall stone
      pancreatitis.

PMID- 22626858
TI  - Relationship between inter-digestive migrating motor complex and quality of life
      in patients after conventional distal gastrectomy for gastric cancer.
AB  - BACKGROUND/AIMS: To clarify the significance of duodenal interdigestive migrating
      complex (IMMC) in patients after conventional distal gastrectomy (COG), we
      studied the relationships between lMMC and postoperative quality of life (QOL).
      METHODOLOGY: A total of 48 patients (32 males, 16 females; 39 to 68 years, mean,
      57.4 years) at two years after CDG for gastric cancer (Billroth I, D2 lymph node
      dissection, curability A) were divided into two groups (IMMC-positive group; 34
      patients, IMMC-negative group; 14 patients) according to the occurrence of IMMC
      from duodenum and their postoperative QOL was compared. RESULTS: IMMC was only
      found from the duodenum, and not from the remnant stomach. 1) Patients in the
      IMMC-positive group had evidently more appetite and ate more food with less
      decrease in body weight compared with the IMMC-negative group; 2) Patients in the
      IMMC-positive group had clearly less symptoms such as early dumping symptoms,
      symptoms of reflux esophagitis, nausea, abdominal pain, diarrhea, abdominal
      fullness, borborygmus and diarrhea compared with the negative group. CONCLUSIONS:
      The IMMC-positive group showed more satisfactory QOL compared with the negative
      group.

PMID- 22626857
TI  - VEGF-C: an indicator of lymph node metastasis for patients that underwent
      esophagectomy.
AB  - BACKGROUND/AIMS: To investigate the expression of vascular endothelial growth
      factor-C (VEGF-C) and its relationship to lymph node metastasis in esophageal
      squamous cell cancer after esophagectomy. METHODOLOGY: The expression of VEGF-C
      protein was detected by immunohistochemistry. Kaplan-Meier method was performed
      to calculate the survival rate. Cox regression multivariate analysis was
      performed to determine independent prognostic factors. RESULTS: The difference of
      VEGF-C protein expression in Tl, T2 and T3 patients was statistically significant
      (p=0.031). The expression of VEGF-C protein in patients with lymph node
      metastasis was significantly higher than those without metastasis (p=0.004). VEGF
      C protein expression correlated with significantly worsened 5-year survival for
      all patients as well as those with T3 tumors and N1 nodal status. The result of
      Cox analysis demonstrated that N stage and VEGF-C protein expression were
      independent prognostic factors; the multivariate analyses indicated that the N
      classification is the independent pathological risk factor of VEGF-C expression.
      CONCLUSION: VEGF-C expression was found to be significantly associated with T
      stage and N stage. The patients with VEGF-C protein expression had a
      significantly lower 5-year survival rate than without VEGF-C protein expression.
      Lymph node metastasis and VEGF-C protein expression were independent prognostic
      factors.

PMID- 22626859
TI  - Postnatal effects of prenatal nicotine exposure on body weight, brain size and
      cortical connectivity in mice.
AB  - Maternal smoking results in myriad physical, cognitive, and behavioral effects in
      offspring due to prenatal exposure to nicotine. As the mammalian neocortex
      coordinates sensory integration and higher-order processes including cognition
      and behavioral regulation, it follows that cognitive and behavioral phenotypes of
      prenatal nicotine exposure (PNE) may correlate with, or stem from changes in
      anatomy and physiology of the neocortex. The current study uses a prenatal
      nicotine mouse model to determine effects of PNE on body weight, brain weight,
      brain length and development of neocortical circuitry, including thalamocortical
      afferents (TCAs) and intraneocortical connections (INCs). Although dam nutrition,
      dam weight gain and litter size were not significantly affected by nicotine
      treatment, PNE resulted in lower newborn birth weight, brain weight and length.
      Interestingly, the reduction of body weight, brain weight, and brain length
      observed in newborn PNE mice compared to control mice was no longer present at
      postnatal day (P) 10. A morphological study of somatosensory and visual TCAs and
      INCs shows no major defects in areal patterning of these connections. These data
      add to a growing body of literature on the neurobiological effects of PNE by
      providing new information on the time course of PNE-related change in the
      postnatal brain.

PMID- 22626860
TI  - Comparison of the kidney fungal burden in experimental disseminated candidiasis
      by species of the Candida parapsilosis complex treated with fluconazole,
      amphotericin B and caspofungin in a temporarily neutropenic murine model.
AB  - BACKGROUND: The efficacy of fluconazole (FLU), amphotericin B (AMB) and
      caspofungin (CAS) was tested against three Candida orthopsilosis, three C.
      metapsilosis and two C. parapsilosis sensu stricto isolates in neutropenic mice.
      METHODS: Mice were immunosuppressed by 200 mg/kg cyclophosphamide. Five-day
      intraperitoneal treatment was started 24 h after infection. Kidney burden was
      analyzed using the Kruskal-Wallis test. RESULTS: FLU 10 and 20 mg/kg as well as
      AMB 1 mg/kg significantly decreased the fungal burden (p < 0.05) for all eight
      isolates of the three species. CAS 2 and 5 mg/kg were efficacious against all C.
      orthopsilosis and C. metapsilosis isolates (p < 0.05), but only 5 mg/kg CAS was
      effective against C. parapsilosis isolates (p < 0.05). CONCLUSIONS: The efficacy
      of FLU and AMB against the three species was comparable. Though the activity of
      CAS was higher against C. orthopsilosis and C. metapsilosis, the current
      treatment guidelines for C. parapsilosis sensu stricto seem to be applicable to
      other 'psilosis' species.

PMID- 22626861
TI  - Infrasonic noise induces axonal degeneration of cultured neurons via a Ca2+
      influx pathway.
AB  - Infrasound is a kind of environmental noise. It can evoke biological resonance in
      organismic tissues including the central nervous system (CNS), causing
      displacement and distortion of cellular architectures. Several studies have
      revealed that certain intensity infrasound can impair normal functions of the
      brain, but the underlying mechanisms still remain largely unknown. Growing
      evidence has demonstrated that axonal degeneration is responsible for a variety
      of CNS dysfunctions. To explore whether neuronal axons are affected under
      infrasonic insults, we exposed cultured hippocampal neurons to infrasound with a
      frequency of 16 Hz and a pressure level of 130 dB for 1h, and examined the
      morphological and molecular changes of neuronal axons by immunocytochemistry and
      Western blotting, respectively. Our results showed that infrasound exposure
      significantly resulted in axonal degeneration of cultured hippocampal neurons,
      which was relatively independent of neuronal cell death. This infrasound-induced
      axonal degeneration can be significantly blocked by Ca2+ chelator EGTA and Rho
      kinase inhibitor Fasudil, but not by proteasome inhibitor MG132. Moreover,
      calcium imaging and RhoA activation assays revealed a great enhancement of Ca2+
      influx within axons and RhoA activation after infrasound exposure, respectively.
      Depletion of Ca2+ by EGTA markedly inhibited this Ca2+ influx and attenuated RhoA
      activation as well. Thus, our findings revealed that axonal degeneration may be
      one of the important mechanisms underlying infrasound-induced CNS impairment, and
      Ca2+ influx pathway is likely implicated in the process.

PMID- 22626862
TI  - Impact of the Parkinson's disease medication protocol program on nurses'
      knowledge and management of Parkinson's disease medicines in acute and aged care
      settings.
AB  - AIMS: To determine the impact of a Parkinson's medicine education program on
      nurses' knowledge and practices in two settings where people with Parkinson's
      disease are cared for: hospitals and residential aged care facilities. The
      Parkinson's Disease Medication Protocol Program aimed to increase nurse knowledge
      of Parkinson's medication administration and safety in care management in order
      to improve health outcomes, function and well-being for the person with
      Parkinson's. BACKGROUND: The ageing demographic of the developed world is
      concomitant with an increase in chronic disease, with Parkinson's disease being
      one of the most debilitating and costly. Individually complex medication regimens
      and unique spectrums of symptoms require disease-specific knowledge in nurses.
      People with Parkinson's disease admitted to hospitals and/or living in
      residential aged care facilities often have multiple co-morbidities, rendering
      care more complex still. Nurse ignorance of Parkinson's disease medicines, their
      uses, side effects and administration regimens, and safe care practices, can
      cause unnecessary distress and dysfunction for the person. METHOD: The two pilot
      studies employed an eighteen month pre/post-test/follow up design at different
      time frames, using a questionnaire developed by the study team and an expert
      panel to evaluate nurses' self-assessed 'perceived' knowledge and actual
      knowledge of Parkinson's disease, Parkinson's medicines and safe care practices,
      and satisfaction with the targeted Parkinson's education program.
      RESULTS/FINDINGS: Nurses in the hospital pilot (2006/8) revealed deficits in pre
      test perceived and actual knowledge levels, which increased significantly at post
      test and follow-up. In contrast, in the residential aged care pilot (2008/10) the
      nurses had higher perceived and actual (correct) knowledge relevant to experience
      at pre-test and these levels increased at follow-up. Both pilot study cohorts
      were very satisfied with the PDMPP as an education and support vehicle in
      Parkinson's management. CONCLUSION: These study results concur with the
      international literature which identifies that without targeted clinical
      education nurses do not necessarily have sufficient knowledge to effectively
      manage Parkinson's medicines and avoid unnecessary negative outcomes arising from
      delays, errors and omissions, nor do they know how to provide safe and effective
      care for persons with Parkinson's. A well-developed and resourced Parkinson's
      medicine education program, such as the PDMPP, has the potential to improve
      deficits in clinical practice.

PMID- 22626863
TI  - Grading practice: an evaluation one year on.

PMID- 22626864
TI  - Neighborhood-level socioeconomic and urban land use risk factors of canine
      leptospirosis: 94 cases (2002-2009).
AB  - Associations of housing, population, and agriculture census variables, and
      presence near public places were retrospectively evaluated as potential risk
      factors for canine leptospirosis using Geographic Information Systems (GIS). The
      sample population included 94 dogs positive for leptospirosis based on a positive
      polymerase chain reaction test for leptospires on urine, isolation of leptospires
      on urine culture, a single reciprocal serum titer of 12,800 or greater, or a four
      fold rise in reciprocal serum titers over a 2-4 week period; and 185 dogs
      negative for leptospirosis based on a negative polymerase chain reaction test and
      reciprocal serum titers less than 400. Multivariable logistic regressions
      revealed different risk factors among different census units; however, houses
      lacking complete plumbing facilities [OR=2.80, 95% C.I.=1.82, 4.32 (census unit,
      block group); OR=1.36, 95% C.I.=1.28, 1.45 (census tract); OR=3.02, 95%
      C.I.=2.60, 3.52 (county)]; and poverty status by age (18-64) [OR=2.04, 95%
      C.I.=1.74, 2.39 (block group); OR=1.53, 95% C.I.=1.41, 1.67 (census tract); and
      OR=1.62, 95% C.I.=1.50, 1.76 (county)] were consistent risk factors for all
      census units. Living within 2500 m of a university/college and parks/forests were
      also significantly associated with leptospirosis status in dogs. Dogs that live
      under these circumstances are at higher risk for leptospirosis and pet owners
      should consider vaccination.

PMID- 22626865
TI  - Inhibition and avoidance of mRNA degradation by RNA viruses.
AB  - The cellular mRNA decay machinery plays a major role in regulating the quality
      and quantity of gene expression in cells. This machinery involves multiple
      enzymes and pathways that converge to promote the exonucleolytic decay of mRNAs.
      The transcripts made by RNA viruses are susceptible to degradation by this
      machinery and, in fact, can be actively targeted. Thus, to maintain gene
      expression and replication, RNA viruses have evolved a number of strategies to
      avoid and/or inactivate aspects of the cellular mRNA decay machinery. Recent work
      uncovering the mechanisms used by RNA viruses to maintain the stability of their
      transcripts is described below.

PMID- 22626866
TI  - 'Omics' of the mammalian gut--new insights into function.
AB  - To understand the role of gut microbes in host health, it is imperative to probe
      their genetic potential, expression, and ecological status. The current high
      throughput sequencing revolution, in addition to advances in mass spectrometry
      based proteomics, have recently enabled deep access to these complex
      environments, and are revealing important insights into the roles of the
      gastrointestinal (GI) microbiota in host physiology and health. This review
      discusses examples of how the integration of cutting-edge 'meta-omics'
      technologies are providing new knowledge about the relationships between host
      health status in mammals and the microbes inhabiting the GI tract. In addition,
      we address some promises that these techniques hold for future therapeutic and
      diagnostic applications.

PMID- 22626867
TI  - Polarity- and valence-dependent effects of prefrontal transcranial direct current
      stimulation on heart rate variability and salivary cortisol.
AB  - Recent evidence has supported the notion that the hypothalamic-pituitary-adrenal
      (HPA) and the sympatho-adreno-medullary (SAM) systems are modulated by cortical
      structures such as the prefrontal cortex. This top-down modulation may play a
      major role in the neuroendocrine changes associated with stressful events. We
      aimed to investigate further this hypothesis by modulating directly prefrontal
      cortex excitability using transcranial direct current stimulation (tDCS) - a non
      invasive, neuromodulatory tool that induces polarity-dependent changes in
      cortical excitability - and measuring effects on salivary cortisol and heart rate
      variability as proxies of the HPA and SAM systems. Twenty healthy participants
      with no clinical and neuropsychiatric conditions were randomized to receive
      bifrontal tDCS (left anodal/right cathodal or left cathodal/right anodal) or sham
      stimulation, in a within-subject design. During each stimulation session, after a
      resting period, subjects were shown images with neutral or negative valence. Our
      findings showed that excitability enhancing left anodal tDCS induced a decrease
      in cortisol levels. This effect is more pronounced during emotional negative
      stimuli. Moreover, vagal activity was higher during left anodal tDCS and
      emotional negative stimuli, as compared to sham stimulation and neutral images.
      We also observed an association between higher mood scores, higher vagal
      activation and lower cortisol levels for anodal stimulation. Subjective mood and
      anxiety evaluation revealed no specific changes after stimulation. Our findings
      suggest that tDCS induced transient, polarity specific modulatory top-down
      effects with anodal tDCS leading to a down-regulation of HPA and SAM systems.
      Further research using tDCS and neuroendocrine markers should explore the
      mechanisms of stress regulation in healthy and clinical samples.

PMID- 22626868
TI  - Trait mindfulness modulates neuroendocrine and affective responses to social
      evaluative threat.
AB  - BACKGROUND: Individual differences in mindfulness have been associated with
      numerous self-report indicators of stress, but research has not examined how
      mindfulness may buffer neuroendocrine and psychological stress responses under
      controlled laboratory conditions. The present study investigated the role of
      trait mindfulness in buffering cortisol and affective responses to a social
      evaluative stress challenge versus a control task. METHODS: Participants
      completed measures of trait mindfulness, perceived stress, anxiety, and fear of
      negative evaluation before being randomized to complete the Trier Social Stress
      Test (TSST; Kirschbaum et al., 1993) or a control task. At points throughout the
      session, participants provided five saliva samples to assess cortisol response
      patterns, and completed four self-report measures of anxiety and negative affect
      to assess psychological responses. RESULTS: In accord with hypotheses, higher
      trait mindfulness predicted lower cortisol responses to the TSST, relative to the
      control task, as well as lower anxiety and negative affect. These relations
      remained significant when controlling for the role of other variables that
      predicted cortisol and affective responses. CONCLUSIONS: The findings suggest
      that trait mindfulness modulates cortisol and affective responses to an acute
      social stressor. Further research is needed to understand the neural pathways
      through which mindfulness impacts these responses.

PMID- 22626869
TI  - Role of LXR in trout adipocytes: target genes, hormonal regulation, adipocyte
      differentiation and relation to lipolysis.
AB  - In the present study, we describe an initial approach to investigate the role of
      LXR in fish adipose tissue. Rainbow trout (Oncorhynchus mykiss) isolated
      adipocytes were incubated with LXR agonists, unsaturated fatty acids, tumour
      necrosis factor-alpha (TNFalpha), insulin or growth hormone (GH) for 6h and LXR
      expression was analyzed. Lipolysis was measured after incubation with one of the
      LXR agonists and LXR expression was compared with levels of lipolysis. LXR
      expression was also analyzed during the differentiation of adipocytes in culture.
      The incubations with agonists in isolated adipocytes indicated that ATP-binding
      cassette transporter A1 (ABCA1) is an LXR target gene, but lipoprotein lipase
      (LPL), fatty acid synthase (FAS), hormone-sensitive lipase (HSL) and peroxisome
      proliferator-activated receptor (PPARs) are not. LXR agonists also induced LXR
      expression and raised lipolysis levels. Besides, LXR expression was upregulated
      in parallel with basal lipolysis. LXR mRNA expression was regulated by
      unsaturated fatty acids, insulin, TNFalpha and GH in isolated adipocytes.
      Besides, LXR showed an upregulation during adipocyte differentiation. All these
      data indicate that LXR is involved in orchestrating the transcriptional
      regulatory network in trout adipocyte lipid metabolism, specifically, in
      cholesterol transport, adipocyte differentiation and lipolysis.

PMID- 22626870
TI  - Cleavage mediated by the catalytic domain of bacterial RNase P RNA.
AB  - Like other RNA molecules, RNase P RNA (RPR) is composed of domains, and these
      have different functions. Here, we provide data demonstrating that the catalytic
      (C) domain of Escherichia coli (Eco) RPR when separated from the specificity (S)
      domain mediates cleavage using various model RNA hairpin loop substrates.
      Compared to full-length Eco RPR, the rate constant, k(obs), of cleavage for the
      truncated RPR (CP RPR) was reduced 30- to 13,000-fold depending on substrate.
      Specifically, the structural architecture of the -1/+73 played a significant role
      where a C(-1)/G(+73) pair had the most dramatic effect on k(obs). Substitution of
      A(248) (E. coli numbering), positioned near the cleavage site in the RNase P
      substrate complex, with G in the CP RPR resulted in 30-fold improvement in rate.
      In contrast, strengthening the interaction between the RPR and the 3' end of the
      substrate only had a modest effect. Interestingly, although deleting the S-domain
      gave a reduction in the rate, it resulted in a less erroneous RPR with respect to
      cleavage site selection. These data support and extend our understanding of the
      coupling between the distal interaction between the S-domain and events at the
      active site. Our findings will also be discussed with respect to the structure of
      RPR derived from different organisms.

PMID- 22626871
TI  - Endovascular vs open repair for ruptured abdominal aortic aneurysm.
AB  - OBJECTIVE: Endovascular repair (EVAR) of ruptured abdominal aortic aneurysm
      (rAAA) has become first-line therapy at our institution and is performed under a
      standardized protocol. We compare perioperative mortality, midterm survival, and
      morbidity after EVAR and open surgical repair (OSR). METHODS: Records were
      retrospectively reviewed from May 2000 to September 2010 for repair of infrarenal
      rAAAs. Primary end points included perioperative mortality and midterm survival.
      Secondary end points included acute limb ischemia, length of stay, ventilator
      dependent respiratory failure, myocardial infarction, renal failure, abdominal
      compartment syndrome, and secondary intervention. Statistical analysis was
      performed using the t-test, chi(2) test, the Fisher exact test, and logistic
      regression calculations. Midterm survival was assessed with Kaplan-Meier analysis
      and Cox proportional hazard models. RESULTS: Seventy-four infrarenal rAAAs were
      repaired, 19 by EVAR and 55 by OSR. Despite increased age and comorbidity in the
      EVAR patients, perioperative mortality was 15.7% for EVAR, which was
      significantly lower than the 49% for OSR (odds ratio, 0.19; 95% CI, 0.05-0.74; P
      = .008). Midterm survival also favored EVAR (hazard ratio, 0.40; 95% CI, 0.21
      0.77; P = .028, adjusted for age and sex). Mean follow-up was 20 months, and 1
      year survival was 60% for EVAR vs 45% for OSR. Mean length of stay for patients
      surviving >1 day was 10 days for EVAR and 21 days for OSR (P = .004). Ventilator
      dependent respiratory failure was 5% in the EVAR group vs 42% for OSR (odds
      ratio, 0.08; 95% CI, 0.01-0.62; P = .001). CONCLUSIONS: EVAR of rAAA has a
      superior perioperative survival advantage and decreased morbidity vs OSR.
      Although not statistically significant, overall survival favors EVAR. We
      recommend that EVAR be considered as the first-line treatment of rAAAs and
      practiced as the standard of care.

PMID- 22626872
TI  - Legal implications of pushing the endovascular envelope.
AB  - Endovascular technology continues to improve for the treatment of vascular
      disease. However, application of these technologies without first obtaining
      proper informed consent may result in medical malpractice litigation. Similarly,
      use of these technologies without proper government and/or hospital approval may
      result in both criminal and/or civil liability. Care must be taken when pushing
      the envelope of endovascular interventions.

PMID- 22626873
TI  - Variability in hemoglobin A1c predicts all-cause mortality in patients with type
      2 diabetes.
AB  - BACKGROUND: To evaluate the relationship between hemoglobin A1c variability and
      all-cause mortality in type 2 diabetic patients. METHODS: This was a
      retrospective cohort study in type 2 diabetic patients followed for at least 2
      years between 2003 and 2009. A1C variability was determined from the standard
      deviation or coefficient of variation of serial A1C values (A1C(SD) or A1C(CV)).
      Subjects were categorized into either the high or low A1C variability group
      according to their A1C(CV) median. Hazard ratios (HRs) of various factors for all
      cause mortality were determined from Cox's proportional hazard models. RESULTS: A
      total of 881 subjects (422 men, 459 women) were included and 73 (8.3%) died
      during follow-up. The follow-up period was 4.7 +/- 2.3 years. All-cause mortality
      was higher in subjects with high A1C(CV) (11.0% vs. 5.4%, p=0.002). In the Kaplan
      Meier failure curve, subjects with higher A1C(CV) demonstrated a trend of higher
      mortality (p=0.1). In multivariate Cox's proportional hazards models, A1C(SD) and
      A1C(CV) significantly predicted all-cause mortality with an HR of 1.987 (p=0.02)
      and 1.062 (p=0.013), respectively, after adjusting for age, gender, body mass
      index, duration of diabetes, mean systolic blood pressure, use of
      antihypertensives and statins, mean LDL-cholesterol, smoking status, chronic
      kidney disease, and mean A1C values (A1C(MEAN)). The ability of A1C(SD) and
      A1C(CV) to predict all-cause mortality was more evident in subjects with
      relatively low A1C(MEAN.) CONCLUSIONS: A1C variability is an important risk
      factor for all-cause mortality in type 2 diabetic patients.

PMID- 22626874
TI  - Luteolin ameliorates cardiac failure in type I diabetic cardiomyopathy.
AB  - OBJECTIVE: The study aimed to determine whether luteolin can confer
      cardioprotective effects against diabetic cardiomyopathy in relation to specific
      and quantitative markers of oxidative stress. METHODS: We examined diabetic
      cardiomyopathy by left ventricular hemodynamic analysis. Myocardial oxidative
      stress was assessed by measuring the activity of superoxide dismutase (SOD) as
      well as the level of malondialdehyde (MDA). Hypolipidaemic effects of luteolin
      were also investigated in STZ-induced diabetic rats. Myocardial Akt/PKB
      phosphorylation, heme oxygenase-1 (HO-1) and connective tissue growth factor
      (CTGF) protein levels were measured by Western blot in all rats at the end of the
      study. RESULTS: This study showed a significant increase in serum triacylglycerol
      (TG), total cholesterol (TC), lower density lipoprotein (LDL), MDA content,
      creatine kinase (CK), lactate dehydrogenase (LDH), and myocardial CTGF and a
      significant decrease in high density lipoprotein (HDL), SOD and Akt
      phosphorylation level in the diabetic group compared to the control group.
      Luteolin treatment induced a significant decrease in serum TG, TC, LDL, MDA, CK,
      LDH, and myocardial CTGF and a significant increase in HDL, SOD and Akt
      phosphorylation levels in comparison with the diabetic group. CONCLUSION: These
      results show that luteolin protects against the progression of diabetes mellitus
      induced cardiac dysfunction by attenuation of myocardial oxidative stress
      probably through its antioxidant properties.

PMID- 22626875
TI  - Vildagliptin selectively ameliorates GLP-1, GLUT4, SREBP-1c mRNA levels and
      stimulates beta-cell proliferation resulting in improved glucose homeostasis in
      rats with streptozotocin-induced diabetes.
AB  - OBJECTIVE: Inhibitors of dipeptidyl peptidase-4 (DPP-4), a key regulator of the
      actions of incretin hormones, exert antihyperglycemic effects in type 2 diabetic
      patients. A major unanswered question concerns the potential ability of DPP-4
      inhibition to have beneficial disease-modifying effects, specifically to
      attenuate loss of pancreatic beta-cell mass and function due to oxidative stress
      induced inflammation. Here, we investigated the effects of a potent and selective
      DPP-4 inhibitor vildagliptin on glycemic control, pancreatic beta-cell mass and
      function, genes and proteins expressions, tumor necrosis factor-alpha, and nitric
      oxide in an n2-STZ diabetic model of rat with defects in insulin sensitivity and
      secretion. METHOD: To induce NIDDM, STZ (sigma chemicals, USA) (90 mg/kg) was
      administered i.p. to a group of 2 days old pups. Another group of pups received
      only saline. The pups were weaned for 21 days, and 6 weeks after the injection of
      STZ, the animals were checked for fasting glucose level (FPG) >=160 mg/dl were
      considered as diabetic. RESULTS: Significant and dose-dependent correction of
      postprandial and fasting hyperglycemia was observed in diabetic rats following 8
      weeks of chronic therapy. Treatment with vildagliptin showed increase in the
      number of insulin-positive beta-cells in islets and improved the expressions of
      genes and proteins are responsible for insulin secretions. In addition, treatment
      of rats with vildagliptin significantly increased insulin content; and decreased
      the nitric oxide and TNF-alpha concentration. CONCLUSION: These findings suggest
      that DPP-4 inhibitors may offer long-lasting efficacy in the treatment of
      diabetes mellitus by modifying the courses of the disease.

PMID- 22626876
TI  - Anemia as a factor related to the progression of proliferative diabetic
      retinopathy after photocoagulation.
AB  - OBJECTIVE: This study aimed to investigate factors that could be related to the
      progression of proliferative diabetic retinopathy in patients treated with
      photocoagulation. METHODS: In this case-control study, a total of 106 patients
      with diabetic retinopathy participated who were treated with photocoagulation. We
      analyzed glycaemia, serum cholesterol, triglycerides, hemoglobin, platelet
      levels, blood pressure measurement, diabetes duration, diabetes and hypertension
      treatment, sex, and age. The statistical analysis was done with t test, chi2
      test, odds ratio (OR), and simple linear regression. RESULTS: We found
      statistical significance in blood glucose level(P=.038), cholesterol level
      (P<.001), and hemoglobin level (P<.001). The simple linear regression was
      significant with blood glucose level (P<.05) and hemoglobin level (P=.001).
      Hemoglobin had a significant result: OR=2.432, 95% CI 1.902-3.115; Pearson
      chi2=16.812; P<.001. CONCLUSIONS: Anemia is an important finding in diabetic
      patients. Anemia is a relevant factor related to the progression of proliferative
      diabetic retinopathy, which can be treated with photocoagulation.

PMID- 22626877
TI  - Response of the epibenthic macrofaunal community to a strong upwelling-driven
      hypoxic event in a shallow bay of the southern Humboldt Current System.
AB  - In January 2008, most of the southern coastal zone of the Humboldt Current System
      was affected by an intense upwelling event. This caused an intrusion of
      equatorial sub-surface water into the coastal zone, generating severe hypoxic
      conditions (<=0.5 ml O(2) l(-1)) three days after the beginning of the event. A
      rapid, massive die-off of marine organisms occurred in Coliumo Bay on January
      3rd, affecting zooplankton, mollusks, crustaceans and fishes. Normal oxygen
      concentrations were observed on January 10th, seven days after the hypoxic event.
      Here we analyze the response of the epibenthic macrofauna community using data
      spanning three years of sampling which encompass the short-term hypoxic
      disturbance in the bay. We found that (i) strong changes in total density, total
      biomass, and diversity occurred immediately after the hypoxic event, negatively
      affecting crustaceans and fishes, while gastropods were favored, (ii) initial
      changes were reverted over a period of three months, (iii) on an inter-annual
      time scale, species richness and diversity decreased following the hypoxic event.
      Total density increased strongly, but total biomass showed no clear inter-annual
      trend. These results show that, while initial recovery from hypoxia was fast,
      over longer time scales the community exhibited a shift to an alternative
      structure dominated principally by Nassariid scavenger species.

PMID- 22626878
TI  - Effect of stroke volume variability- guided intraoperative fluid restriction on
      gastrointestinal functional recovery.
AB  - To investigate the effect of stroke volume variability(SVV)-guided intraoperative
      fluid restriction on gastrointestinal functional recovery and postoperative
      outcome after gastrointestinal surgery. Forty ASA I-II patients undergoing
      elective gastrointestinal surgery were randomly divided into 2 groups (n=20
      each):group A routine fluid administration and group B restricted fluid
      administration. SW value was maintained at 5-7 in group A and 11-13 in group B.
      All patients received general anesthesia, tracheal catheterized and mechanical
      ventilation. Hemodynamic monitoring parameters (MBP, HR, CVP, CO) were noted at 5
      time points. The hemodynamic parameters were maintained within normal limits
      during operation in both groups. The intraoperative intravenous fluid volume in
      group B was significant less than in group A (p<0.01).Urine output in group A was
      significant less than in group B (p<0.05). Stroke volume variation measured from
      Edwards Flotrac sensor and Edwards Vigileo monitor could be a security and
      sensitive parameter as an index of volume administration. In elective
      gastrointestinal surgery, volume resuscitation with a goal SVV of11-13 not only
      reduced intravenous fluid volume but also maintained the stable hemodynamic and
      tissue perfusion, enhanced gastrointestinal functional recovery and reduced the
      length of hospital stay

PMID- 22626879
TI  - Regulatory T-cell responses in chronic hepatitis B patients treated with
      nucleos(t)ide analogs compared with healthy subjects and untreated infected
      individuals.
AB  - BACKGROUND/AIMS: The purpose of this prospective case-control study was to
      evaluate the clinical effects and host immune response in patients with chronic
      hepatitis B (CHB) treated with either entecavir (ETV)or adefovir dipivoxil (ADV).
      METHODOLOGY: Forty-two patients diagnosed with CHB were recruited and randomly
      assigned to receive either ADV (n=19) or ETV(n=18) and were followed for a
      minimum of 96 weeks.Serum hepatitis B virus (HBV) DNA, hepatitis B e antigen and
      antibody (HBeAg, HBeAb), alanine amino-transferase (ALT) and aspartate
      aminotransferase(AST) were measured at baseline and every 24 weeks until study
      completion. After 96 weeks of therapy, regulatory T-cells (Tregs) were measured
      in the patients treated with ETV or ADV. RESULTS: Significant decreases in serum
      ALT, AST and HBV DNA, but not in HBeAgor HbeAb, were noted in the treatment
      group. The ra-tios of CD4+CD25+ and CD4+CD25+CD45RO+CD125+in CD4+ T-cells were
      significantly higher in the untreated group compared to those in the ETV and ADV
      groups. Treg profiles were significantly altered in CHB patients after 96 weeks
      of nucelos(t)ide therapy HBV-infected individuals. CONCLUSIONS: Study results
      support the hypothesis that Tregs play a role in regulating the immune response
      in patients with CHB.

PMID- 22626880
TI  - Is the TissueLink dissecting sealer a better liver resection device than clamp
      crushing? A meta-analysis and system review.
AB  - BACKGROUND/AIMS: Liver resection is the most effective treatment for selected
      patients with primary or metastatic hepatic tumor and many liver resection
      techniques have tried to minimize blood loss. The objective of the present study
      was to examine whether TissueLink dissection sealer (DS) was superior to clamp
      crushing (CC) technique for liver transection or not. METHODOLOGY: MEDLINE,
      Pubmed, Ovid and Cochrane Library electronic databases were used to search for
      studies without language and time period restrictions. RESULTS: Four clinical
      trials with 276 patients were involved. We evaluated intraoperative blood loss,
      postoperative morbidity, postoperative biliary leakage, transfusion rate,
      operation time,hospital stay duration, postoperative mortality,transection time,
      blood loss in liver transection and pertran section area, transection speed, AST
      and TBIL and found no statistical differences between the DS and CC groups.
      Sensitive analysis showed transection time was longer in the former group. In
      addition, there was no apparent publication bias concerning intraoperative blood
      loss. CONCLUSIONS: In summary, we could not draw a firm conclusion that DS is
      superior to CC in liver resection of transection and the advantage of TissueLink
      dissecting sealer should be evaluated

PMID- 22626881
TI  - Dopamine-NMDA receptor interactions: twenty years later.

PMID- 22626882
TI  - The right ventricle in health and disease: insights into physiology,
      pathophysiology and diagnostic management.
AB  - Until recently, the right ventricle (RV) received little attention in adult
      patients with congenital heart disease and even less attention in the setting of
      acquired heart failure. However, in the last two decades, our perspective towards
      the right side of the heart has begun to change. Advances in imaging modalities
      have permitted the accurate study of RV physiology and made it apparent that RV
      function is an important determinant of prognosis in heart failure irrespective
      of the underlying etiology. This article summarizes the existing data on the
      unique anatomical and physiological features of the RV. The hemodynamic
      conditions and cellular and biochemical pathways that lead to right heart failure
      are presented. Moreover, the imaging modalities that aid in the assessment of RV
      structure and function are described and the importance of the diagnostic and
      prognostic information they provide is discussed. 

PMID- 22626883
TI  - Comparison of PR intervals determined by fetal magnetocardiography and pulsed
      Doppler echocardiography.
AB  - OBJECTIVE: In clinical practice, measurement of mechanical PR interval (mPR) with
      pulsed Doppler echocardiography is a standard method used to estimate the
      atrioventricular conduction time in the fetus. However, fetal echocardiography
      does not directly reflect the electrical properties of the heart. Technological
      advances in fetal magnetocardiography (fMCG) have allowed recording of the
      electrical PR interval (ePR) with high time resolution. The aim of this study was
      to clarify the differences between ePR and mPR. METHODS: The study subjects were
      295 normal human fetuses (gestational age, range 20.4-41.4 weeks) who underwent
      fMCG, and 135 of them underwent fetal echocardiography 15-90 min before or after
      fMCG. The ePR was measured using the fMCG, and the mPR was determined by two
      pulsed Doppler methods, simultaneous recording of the left ventricular inward and
      outward flow (LV in/out) (n = 135) and superior vena cava and ascending aorta
      (SVC/aAo) (n = 84). RESULTS: The ePR showed a significant, but weak, positive
      correlation with gestational age (r = 0.162, p = 0.0053). The mPR was
      significantly longer than the ePR (p < 0.0001), with mean differences of 14.6%
      (95% limits of agreement -10.7, 39.9) for the LV in/out method and 14.7% (95%
      limits of agreement -8.6, 38.0) for the SVC/aAo method. CONCLUSION: Our results
      point to the risk of overestimation of the atrioventricular conduction time when
      the mPR is used, and the need for careful interpretation of PR prolongation
      determined by mPR.

PMID- 22626884
TI  - The R-rich motif of Beet black scorch virus P7a movement protein is important for
      the nuclear localization, nucleolar targeting and viral infectivity.
AB  - Beet black scorch virus (BBSV) encodes three movement proteins (P7a, P7b and P5')
      that facilitate its cell-to-cell movement. An arginine-rich motif of P7a N
      terminus was found to determine nuclear and nucleolar localization. Amino acids
      substitution or deletion of the R-rich motif interfered with P7a nuclear and
      nucleolar localization. Bimolecular fluorescence complementation (BiFC) assays
      revealed that P7a protein interacted with Nicotiana benthamiana nuclear import
      factor importin alpha, suggesting that P7a is translocated into the nucleus by
      the classical importin alpha/beta-dependent pathway. Moreover, P7a also
      interacted with the nucleolar protein fibrillarin. Mutations in the R-rich motif
      of P7a diminished P7a interactions with importin alpha and fibrillarin,
      influenced viral replication in Nicotiana benthamiana protoplasts and altered the
      symptom phenotype and viral RNA accumulation in Chenopodium amaranticolor plants.
      These results demonstrate that the R-rich motif of P7a is correlated with nuclear
      and nucleolar localization, viral replication and virus infection.

PMID- 22626885
TI  - A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms
      - an application for paediatric dosage form selection.
AB  - The design and selection of new pharmaceutical dosage forms involves the careful
      consideration and balancing of a quality target product profile against technical
      challenges and development feasibility. Paediatric dosage forms present
      particular complexity due to the diverse patient population, patient compliance
      challenges and safety considerations of this vulnerable population. This paper
      presents a structured framework for assessing the comparative benefits and risks
      of different pharmaceutical design options against pre-determined criteria
      relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk
      framework has then been applied to three hypothetical, but realistic, scenarios
      for paediatric dosage forms in order to explore its utility in guiding dosage
      form design and formulation selection. The approach allows a rigorous, systematic
      and qualitative assessment of the merits and disadvantages of each dosage form
      option and helps identify mitigating strategies to modify risk. The application
      of a weighting and scoring system to the criteria depending on the specific case
      could further refine the analysis and aid decision-making. In this paper, one
      case study is scored for illustrative purposes. However, it is acknowledged that
      in real development scenarios, the generation of actual data considering the very
      specific situation for the patient/product/developer would come into play to
      drive decisions on the most appropriate dosage form strategy.

PMID- 22626886
TI  - A discriminatory intrinsic dissolution study using UV area imaging analysis to
      gain additional insights into the dissolution behaviour of active pharmaceutical
      ingredients.
AB  - For efficient and effective drug development it is desirable to acquire a deep
      understanding of the dissolution behaviour of potential candidate drugs and their
      physical forms as early as possible and with the limited amounts of material that
      are available at that time. Using 3-10mg sample quantities, the ability of a UV
      imaging system is investigated to provide deep mechanistic insight into the
      intrinsic dissolution profiling of a range of compounds and physical forms
      assessed under flow conditions. Physical forms of indomethacin, theophylline and
      ibuprofen were compressed and their solid-state form confirmed before and after
      compression with X-ray methods and/or Raman spectroscopy. Intrinsic dissolution
      rates (IDRs) were determined using the compact's UV-imaging profile. The ratio in
      the IDRs for theophylline anhydrate over hydrate was 2.1 and the ratio for the
      alpha form of indomethacin over the gamma form was approximately 1.7. The
      discriminatory power of the novel UV area visualisation approach was shown to be
      high in that process-induced solid-state dissolution differences post
      micronisation could be detected. Additionally, the scale-down system was able to
      visualise a previously observed increase in ibuprofen IDR with an increase in
      concentration of sodium dodecyl sulphate. The mechanistic dissolution insights
      from the visualisation approach are evident.

PMID- 22626887
TI  - Cystatin B homolog from rock bream Oplegnathus fasciatus: genomic
      characterization, transcriptional profiling and protease-inhibitory activity of
      recombinant protein.
AB  - Cysteine proteases are present in all living organisms and, in animals, function
      in a vast array of physiological and pathological processes. Cysteine protease
      inhibitors act upon the cysteine proteases to regulate their activity. The
      cystatin superfamily of cysteine protease inhibitors has members represented in
      all living organisms studied to date. Here, we report the identification of a new
      member of the family 1 cystatin in Oplegnathus fasciatus rock bream (denoted as
      RbCyt B) and the characterization at the molecular level. The complete genomic
      sequence of RbCyt B consists of three exons and a promoter region. The open
      reading frame (ORF) encodes for a 100 amino acids length polypeptide with a
      single cystatin-like domain and a cysteine protease inhibitor signature motif.
      The conserved N-terminal glycine, glutamine-valine-glycine motif, QxVxG, and a
      variant of the proline-tryptophan, PW, motif were identified. RbCyt B showed
      closest phylogenetic distance to Dicentrarchus labrax cystatin B, and shared up
      to 73% amino acid identity and 90% amino acid similarity with known cystatin B
      genes. RbCyt B mRNA expression was detected in nine different tissues and was
      highly expressed in liver, spleen, gill, brain, intestine, kidney, head kidney,
      and blood, as compared with muscle. In vivo immune stimulation with Edwardsiella
      tarda bacteria caused significant up-regulation of RbCyt B mRNA in head kidney
      and spleen at 24h post-infection (P<0.05). Recombinant RbCyt B was expressed in
      Escherichia coli, and the purified protein demonstrated 82% papain inhibitory
      activity at 500 * 10(-3) MUg MUL(-1) in a concentration-dependent manner. These
      results suggest that RbCyt B is a member of family 1 cystatin with high homology
      to cystatin B, and is a biologically active protein possessing papain inhibitory
      activity and potentially involved in immune responses against invading Gram
      negative bacteria in rock bream.

PMID- 22626888
TI  - Cost-effectiveness of nutritional intervention on healing of pressure ulcers.
AB  - BACKGROUND & AIMS: Pressure ulcers not only affect quality of life among the
      elderly, but also bring a large economic burden. There is limited evidence
      available for the effectiveness of nutritional interventions for treatment of
      pressure ulcers. In Japan, recently, a 60-patient randomized controlled trial of
      nutritional intervention on pressure ulcers demonstrated improvement in healing
      of pressure ulcers, compared with conventional management. To evaluate value for
      money of nutritional intervention on healing of pressure ulcers, cost-effective
      analysis was carried out using these trial results. METHODS: The analysis was
      carried out from a societal perspective. As effectiveness measures, pressure
      ulcer days (PUDs) and quality-adjusted life years (QALYs) were estimated.
      Prevalence of pressure ulcers was estimated by the Kaplan-Meier method. Utility
      score for pressure ulcers is derived from a cross-sectional survey among health
      professionals related to pressure ulcers. Costs (e.g., nutritional interventions
      and management of pressure ulcers) were estimated from trial data during
      observation and follow-up. Stochastic and qualitative sensitivity analyses were
      performed to examine the robustness of results. RESULTS: For observation (12
      weeks) and follow-up (12-week observation plus 4-week follow-up), nutritional
      intervention reduced PUDs by 9.6 and 16.2 per person, and gained 0.226 * 10(-2)
      QALYs and 0.382 * 10(-2) QALYs per person, respectively. In addition, costs were
      reduced by $542 and $881 per person, respectively. This means nutritional
      intervention is dominant (cost savings and greater effectiveness). The
      sensitivity analyses showed the robustness of these results. CONCLUSION: Economic
      evaluation of nutritional intervention on healing pressure ulcers from a small
      randomized controlled trial showed that this intervention is cost saving with
      health improvement. Further studies are required to determine whether this is a
      cost-effective intervention for widespread use.

PMID- 22626889
TI  - Testing the specificity between social anxiety disorder and drinking motives.
AB  - This study tested the specificity of the relationship between social anxiety
      disorder (SAD) and coping drinking motives (versus enhancement drinking motives
      and social drinking motives) within the context of a range of potentially
      confounding variables measured during adolescence (e.g., quantity and frequency
      of alcohol use, coping drinking motives) and substantively important variables
      assessed during young adulthood (e.g., other anxiety disorders and major
      depressive disorder). A sample of high school sophomores and juniors (n=717)
      completed measures of substance use and risk factors during adolescence and were
      then prospectively followed-up in early- and middle-young adulthood, and
      psychiatric diagnoses and drinking motives (i.e., coping, enhancement, and
      social) were assessed each time. Findings indicated that SAD was specifically
      related to coping motives (measured during early-to-middle young adulthood) after
      controlling for the effects of a range of alcohol and mental health variables. In
      addition, adolescent variables predicted young adult drinking motives as did
      major depressive disorder and other anxiety disorders. These findings are
      discussed within a conceptual framework of the functional role (e.g., self
      medication) that drinking motives, and especially coping drinking motives, may
      play in the etiology of alcohol problems and disorders. Implications for
      prevention and treatment interventions are discussed.

PMID- 22626891
TI  - Interference by metabolites and the corresponding troubleshooting during the LC
      MS/MS bioanalysis of G004, a bromine-containing hypoglycemic agent.
AB  - The quantitative determination of drugs in bio-samples may be interfered by the
      drug-related metabolites during the high-throughput LC-MS/MS analysis. When
      quantifying bromine or chlorine containing compounds, the 81Br/37Cl isotopic
      forms of their mono-hydroxylated metabolites after in-source dehydration could
      produce ions which are isobaric with the precursor ions of the parent compounds
      at the 79Br/35Cl isotopic form. In this report, we described the identification
      of an interfering hydroxylated metabolite of G004, a novel bromine-containing
      hypoglycemic agent, during LC-MS/MS analysis of plasma samples. Several different
      MRM transitions were tested and evaluated to minimize the metabolite influence on
      the quantification of G004. Furthermore, the standard addition method using
      incurred samples was used to evaluate the matrix effect caused by the interfering
      metabolite. The lower limit of quantitation of the established method was 0.2
      ng/ml, which was 10 times lower than the existing one. The method was
      successfully applied to investigate the single-dosing pharmacokinetic profile of
      G004 in beagle dogs. The above results indicated that when quantifying chlorine
      or bromine containing compounds, evaluation of the interference from mono
      hydroxylation or dehydrogenation metabolites should be undertaken, and if such
      metabolites existed, their impact on quantification of the parent compounds could
      be eliminated by the proper selection of the MRM transitions.

PMID- 22626890
TI  - Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent
      youth.
AB  - BACKGROUND: In opioid dependent youth there is substantial attrition from
      medication-assisted treatment. If youth at risk for attrition can be identified
      at treatment entry or early in treatment, they can be targeted for interventions
      to help retain them in treatment. METHODS: Opioid dependent adolescents and young
      adults (n=152), aged 15-21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of
      detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in
      combination with 12 weeks of psychosocial treatment. Baseline and early treatment
      related predictors of treatment attrition were identified in each group using
      bivariate and multivariate logistic regression. RESULTS: In the DETOX group 36%
      left between weeks 2 and 4, at the end of the dose taper, while in the BUP group
      only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early
      opioid negative urines, use of any medications in the month prior to treatment
      entry, and lifetime non-heroin opioid use were associated with retention while
      prior 30-day hallucinogen use was associated with attrition. In the DETOX group,
      only use of sleep medications was associated with retention although not an
      independent predictor. A broad range of other pre-treatment characteristics was
      unrelated to attrition. CONCLUSIONS: Prompt attention to those with early non
      adherence to medication or an early opioid positive urine, markers available in
      the first 2 weeks of treatment, may improve treatment retention. Extended Bup/Nal
      treatment appeared effective in improving treatment retention for youth with
      opioid dependence across a wide range of demographics, and pre-treatment clinical
      characteristics.

PMID- 22626893
TI  - Simultaneous determination in hair of multiclass drugs of abuse (including THC)
      by ultra-high performance liquid chromatography-tandem mass spectrometry.
AB  - A simple procedure for the quantitative determination in hair samples of 13
      common drugs of abuse or metabolites (morphine, 6-acetylmorphine, codeine,
      amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4
      methylenedioxymethamphetamine, 3,4-methylenedioxyethylamphetamine,
      benzoylecgonine, cocaine, buprenorphine, methadone and Delta(9)
      tetrahydrocannabinol) has been developed and fully validated. The analytes were
      extracted from the matrix by a simple overnight incubation with methanol at 55 
      degrees C. An aliquot of the extract was directly injected into an ultra-high
      performance liquid chromatography system equipped with Waters Acquity UHPLC BEH
      C18 column (100 mm * 2.1mm, 1.7 MUm). The mobile phase eluted with a linear
      gradient (water/formic acid 5 mM:acetonitrile; v:v) from 98:2 to 0:100 in 4.5
      min, followed by isocratic elution at 100% B for 1.0 min. The flow rate was 0.6
      mL/min and the total run time was 8.0 min including re-equilibration at the
      initial conditions. The compounds were revealed by a triple quadrupole mass
      spectrometer operating in the selected reaction monitoring mode. The absence of
      matrix interferents, together with excellent repeatability of both retention
      times and relative abundances of diagnostic transitions, allowed the correct
      identification of all analytes tested. The method proved linear in the interval
      from the limit of quantification to 5.0 ng/mg (1.0 ng/mg for Delta9
      tetrahydrocannabinol) with correlation coefficient values ranging from 0.9970 to
      0.9997. Quantitation limits were below the cut-off values recommended by the
      Society of Hair Testing and ranged from 0.02 to 0.08 ng/mg. Application of the
      present UHPLC-MS/MS procedure and instrumentation to hair analysis allows high
      sample-throughput, together with excellent sensitivity and selectivity, in
      workplace drug-screening controls and forensic investigations. These qualities,
      combined with minimal sample workup, make the cost of this screening affordable
      for most private and public administrations.

PMID- 22626892
TI  - Development and validation of a liquid chromatography-tandem mass spectrometry
      method for quantification of decitabine in rat plasma.
AB  - Decitabine is chemically unstable at physiological temperature and pH. In
      addition, the bioanalysis of decitabine is easily interfered by endogenous 2
      deoxycytidine. A simple, sensitive and specific LC-MS/MS method was developed for
      the analysis of decitabine in rat plasma. No exogenous stabilizers were used to
      prevent the degradation of decitabine in rat plasma. After deproteinized with
      acetonitrile at room temperature, rat plasma samples were analyzed on a Hypersil
      APS-2 NH2 column interfaced with a triple quadrupole tandem mass spectrometer in
      positive electrospray ionization mode. Decitabine was completely separated from 2
      deoxycytidine using gradient elution of water (solvent A) and acetonitrile
      (solvent B) at a flow rate of 1 mL/min. To quantify decitabine and daidzin
      (internal standard), respectively, multiple reaction monitoring (MRM) transitions
      of m/z 251.1->134.7 and m/z 417.3->255.3 was performed. The assay was linear over
      the concentration range of 5.0-2000 ng/mL. The intra- and inter-day precision was
      within 12.0% in terms of relative standard deviation (RSD%) and the accuracy
      within 5.9% in terms of relative error. The LC-MS/MS method was fully validated
      for its sensitivity, selectivity, stability study, matrix effect and recovery.
      The data indicate that this LC-MS/MS method is a specific and effective method
      for the pharmacokinetic study of decitabine in rat plasma. Compared with the
      previously reported analytical methods, this method showed easy and economic
      sample preparation, good specificity and high sensitivity with less plasma (50
      MUL).

PMID- 22626894
TI  - Determination of the active metabolite of moguisteine in human plasma and urine
      by LC-ESI-MS method and its application in pharmacokinetic study.
AB  - In this study, a sensitive and reproducible electro-spray ionization liquid
      chromatography-mass spectrometry (LC-ESI-MS) method was established to determine
      the concentration of M1, the main active metabolite of moguisteine in human
      plasma and urine. The analysis was performed on a Diamonsil(r) C18(2) column (150
      mm * 4.6 mm, 5 MUm) with the mobile phase consisting of 0.1% formic acid
      acetonitrile (57:43, v/v, pH=3.0) at a flow rate of 0.8 mL min-1. The pseudo
      molecular ions [M+H]+ (m/z 312.2 for M1 and 446.3 for glipizide) were selected as
      the target ions for quantification in the selected ion monitoring (SIM) mode.
      Plasma samples were analyzed after being processed by acidification with formic
      acid and protein precipitation with acetonitrile. Urine samples were
      appropriately diluted with blank urine for analysis. Calibration curve was ranged
      from 0.02 to 8 MUg mL-1. The extraction recovery in plasma was over 90%. Both the
      inter- and intra-day precision values were less than 7.5%, and the accuracy was
      in the range from -6.0% to 6.0%. This is the first reported LC-ESI-MS method for
      analyzing M1 in human plasma and urine. The method was successfully applied to
      the pharmacokinetic study after oral administration of single-dose and multiple
      dose of moguisteine tablets in healthy Chinese subjects.

PMID- 22626895
TI  - A pulse fishery model with closures as function of the catch: conditions for
      sustainability.
AB  - We present a model of single species fishery which alternates closed seasons with
      pulse captures. The novelty is that the length of a closed season is determined
      by the remaining stock size after the last capture. The process is described by a
      new type of impulsive differential equations recently introduced. The main result
      is a fishing effort threshold which determines either the sustainability of the
      fishery or the extinction of the resource.

PMID- 22626896
TI  - Alternative to Ritt's pseudodivision for finding the input-output equations of
      multi-output models.
AB  - Differential algebra approaches to structural identifiability analysis of a
      dynamic system model in many instances heavily depend upon Ritt's pseudodivision
      at an early step in analysis. The pseudodivision algorithm is used to find the
      characteristic set, of which a subset, the input-output equations, is used for
      identifiability analysis. A simpler algorithm is proposed for this step, using
      Grobner Bases, along with a proof of the method that includes a reduced upper
      bound on derivative requirements. Efficacy of the new algorithm is illustrated
      with several biosystem model examples.

PMID- 22626897
TI  - Calcium supplements: bad for the heart?

PMID- 22626898
TI  - Significance of systemic to pulmonary artery collaterals in single ventricle
      physiology: new insights from CMR imaging.

PMID- 22626899
TI  - Prevalence and non-invasive predictors of left main or three-vessel coronary
      disease: evidence from a collaborative international meta-analysis including 22
      740 patients.
AB  - BACKGROUND: Left main disease (LMD) and three-vessel disease (3VD) have important
      prognostic value in patients with coronary artery disease. However, uncertainties
      still exist about their prevalence and predictors in patients with acute coronary
      syndrome (ACS) and also in patients with stable coronary disease. Thus the aim of
      this study was to perform an international collaborative systematic review and
      meta-analysis to appraise the prevalence and predictors of LMD and 3VD. METHODS:
      Medline/PubMed were systematically searched for eligible studies published up to
      2010, reporting multivariate predictors of LMD or 3VD. Study features, patient
      characteristics, and prevalence and predictors of LMD and 3VD were abstracted and
      pooled with random-effect methods (95% CIs). RESULTS: 17 studies (22 740
      patients) were included, 11 focusing on ACS (17 896 patients) and six on stable
      coronary disease (4844 patients). In the ACS subgroup, LMD or 3VD occurred in 20%
      (95% CI 7.2% to 33.4%), LMD in 12% (95% CI 10.5% to 13.5%), and 3VD in 25% (95%
      CI 23.1% to 27.0%). Heart failure at admission and extent of ST-segment elevation
      in lead aVR on 12-lead ECG were the most powerful predictors of LMD or 3VD. In
      the stable disease subgroup, LMD or 3VD was found in 36% (95% CI 18.5% to 48.8%),
      with the most powerful predictors being transient ischaemic dilation during the
      imaging stress test, extent of ST-segment elevation in aVR and V1 during the
      stress test, and hyperlipidaemia. CONCLUSIONS: This meta-analysis demonstrated
      that severe coronary disease-that is, LMD or 3VD-is more common in patients with
      ACS or stable coronary disease than generally perceived, and that simple and low
      cost tools may help in the selection of the most appropriate therapeutic
      approach.

PMID- 22626900
TI  - Associations of dietary calcium intake and calcium supplementation with
      myocardial infarction and stroke risk and overall cardiovascular mortality in the
      Heidelberg cohort of the European Prospective Investigation into Cancer and
      Nutrition study (EPIC-Heidelberg).
AB  - BACKGROUND: It has been suggested that a higher calcium intake might favourably
      modify cardiovascular risk factors. However, findings of an ultimately decreased
      risk of cardiovascular disease (CVD) are limited. Instead, recent evidence warns
      that taking calcium supplements might increase myocardial infarction (MI) risk.
      OBJECTIVE: To prospectively evaluate the associations of dietary calcium intake
      and calcium supplementation with MI and stroke risk and overall CVD mortality.
      METHODS: Data from 23 980 Heidelberg cohort participants of the European
      Prospective Investigation into Cancer and Nutrition study, aged 35-64 years and
      free of major CVD events at recruitment, were analysed. Multivariate Cox
      regression models were used to estimate HRs and 95% CIs. RESULTS: After an
      average follow-up time of 11 years, 354 MI and 260 stroke cases and 267 CVD
      deaths were documented. Compared with the lowest quartile, the third quartile of
      total dietary and dairy calcium intake had a significantly reduced MI risk, with
      a HR of 0.69 (95% CI 0.50 to 0.94) and 0.68 (95% CI 0.50 to 0.93), respectively.
      Associations for stroke risk and CVD mortality were overall null. In comparison
      with non-users of any supplements, users of calcium supplements had a
      statistically significantly increased MI risk (HR=1.86; 95% CI 1.17 to 2.96),
      which was more pronounced for calcium supplement only users (HR=2.39; 95% CI 1.12
      to 5.12). CONCLUSIONS: Increasing calcium intake from diet might not confer
      significant cardiovascular benefits, while calcium supplements, which might raise
      MI risk, should be taken with caution.

PMID- 22626901
TI  - Systemic to pulmonary collateral blood flow influences early outcomes following
      the total cavopulmonary connection.
AB  - BACKGROUND: Systemic to pulmonary collaterals (SPCs) represent an additional and
      unpredictable source of pulmonary blood flow in patients with single ventricle
      physiology following bidirectional superior cavopulmonary connection (BCPC).
      Understanding their influence on patient outcomes has been hampered by
      uncertainty about the optimal method of quantifying SPC flow. OBJECTIVE: To
      quantify SPC flow by cardiac magnetic resonance (CMR) prior to total
      cavopulmonary connection (TCPC) in order to identify preoperative risk factors
      and determine influence on postoperative outcomes. DESIGN: Single centre
      prospective cohort study. SETTING: Tertiary referral centre. PATIENTS: 65
      patients with single ventricle physiology undergoing CMR for preoperative
      assessment of TCPC completion underwent quantification of SPC flow. Clinical
      outcomes of 41 patients in whom TCPC was completed were obtained. MAIN OUTCOME
      MEASURES: Early post-TCPC clinical outcomes associated with SPC flow were
      assessed, including postoperative chest drainage volume, postoperative chest
      drainage duration and length of intensive care and hospital stays. Additionally
      preoperative covariates associated with SPC flow were assessed including age at
      BCPC and CMR, SpO(2) at BCPC and CMR, ventricle type, pulmonary artery (PA) cross
      sectional area and PA pulsatility. Different methods of CMR SPC flow
      quantification were compared. RESULTS: Higher SPC flow was associated with
      increased postoperative chest drain volume (r=0.51, p=0.001), chest drain
      duration (r=0.43, p=0.005), and intensive care unit (r=0.32, p=0.04) and log
      transformed hospital stays (r=0.31, p=0.048). The effect of SPC flow on outcome
      was independent of fenestration, ventricle type and function. Preoperative
      covariates associated with SPC flow included age at BCPC (beta=-0.34, p=0.008),
      SpO(2) at time of CMR (beta=0.34, p=0.004) and branch PA cross-sectional area
      (beta=-0.26, p=0.036), model R(2)=0.34. Moreover, patients with pulsatile
      pulmonary blood flow had lower SPC flow than those without (0.8 vs 1.3 l/min/m(2)
      p=0.012). SPC flow calculated by the difference between pulmonary venous return
      and pulmonary artery flow (l/min/m(2)) showed greatest association with
      preoperative covariates and strongest correlation with postoperative outcomes
      compared with other methods of quantification. CONCLUSIONS: CMR can provide an
      effective measurement of SPC flow prior to TCPC. Young age at BCPC, high
      preoperative oxygen saturation and smaller PAs are associated with increased SPC
      flow, which may promote increased postoperative pleural drainage and lengthen
      recovery.

PMID- 22626902
TI  - Cardiovascular risk age: concepts and practicalities.
AB  - OBJECTIVES: A young person with many risk factors may have the same level of risk
      as an older person with no risk factors. Thus a high-risk 40-year-old may have a
      risk age of 60 years or more. The aim of the study was to derive a generic
      equation for risk age, construct risk age charts, and explore the hypothesis that
      risk age is similar regardless of the cardiovascular disease (CVD) end point
      used. METHODS: The equation was generated by equating the generic formula for 10
      year CVD risk (with unknown risk factor levels) to the generic formula for 10
      year CVD risk in a person with age = x and ideal risk factor levels (total
      cholesterol 4 mmol/l, systolic blood pressure 120 mm Hg, and non-smoker) and
      solving for x. To examine the consistency between risk ages for different end
      points, a risk age based on risk of CVD fatal events and based on risk of fatal
      and non-fatal CVD events was derived for each of the participants in the FINRISK
      population study. The correlation between these risk ages was examined. RESULTS:
      A generic equation for risk age was derived. The generic equation could not be
      used for SCORE (Systematic COronary Risk Evaluation), because the age is included
      in the baseline. Therefore a table of SCORE risk ages was developed by looking up
      the risk age corresponding to each combination of risk factors in the chart. Risk
      age remains similar regardless of the cardiovascular end point used, which
      bypasses the dilemma of whether to use a risk-estimation system based on CVD
      mortality or on the more attractive but less reliable end point of total CVD
      events. On the basis of the equation, risk age is not dependent on baseline
      survival and therefore recalibration is not required. CONCLUSIONS: Risk age is an
      intuitive and easily understood method for communicating about risk, particularly
      in younger patients, and may facilitate lifestyle change in younger patients.
      However, treatment decisions should be based on absolute risk, as recommended by
      guidelines on CVD prevention.

PMID- 22626903
TI  - The athlete's heart.

PMID- 22626904
TI  - Endoscopic vein harvesting: importance of patient selection.

PMID- 22626906
TI  - Isolated tuberculosis of the talonavicular joint in a child.
AB  - Tuberculosis of small bones of foot is a diagnostic dilemma particularly when it
      is isolated. We report a rare case of isolated tuberculosis of navicular bone in
      1a 11-year-old girl that was differently traded for a long time before final
      diagnosis.

PMID- 22626907
TI  - Adeno-associated virus type 2 vector-mediated glial cell line-derived
      neurotrophic factor gene transfer induces neuroprotection and neuroregeneration
      in a ubiquitin-proteasome system impairment animal model of Parkinson's disease.
AB  - BACKGROUND: The impairment of the ubiquitin-proteasome system (UPS) is a cellular
      mechanism underlying the neurodegenerative process in Parkinson's disease (PD). A
      mouse model induced by the selective proteasome inhibitor lactacystin targeting
      on substantia nigra has been demonstrated to be valuable in investigating
      etiopathogenesis and neuroprotection for PD. OBJECTIVE: In the present study, we
      used adeno-associated virus type 2 vector (AAV2) encoding glial cell line-derived
      neurotrophic factor (GDNF) injected into the striatum of this animal model to
      test the effectiveness and possible mechanisms of GDNF gene therapy. RESULTS: Our
      results showed that AAV2-mediated GDNF gene therapy significantly attenuated
      lactacystin-induced loss of nigral dopamine (DA) neurons and striatal DA levels.
      Furthermore, we found that GDNF protein is mostly expressed in astrocytes in the
      subventricular zone (SVZ) and dentate gyrus (DG). AAV2-mediated GDNF therapy can
      induce neurogenesis in the SVZ and DG, and increase the number of nigral newborn
      DA neurons. CONCLUSION: These data indicate that AAV2-mediated GDNF gene therapy
      can protect the nigral DA neurons from the UPS impairment-induced degeneration,
      which may partly result from the nigral DA neuron regeneration in the brain, and
      such experimental results may have implications for the treatment of PD.

PMID- 22626908
TI  - Limitations and sources of bias in clinical knee cartilage research.
AB  - PURPOSE: The purpose of this study was to systematically review the limitations
      and biases inherent to surgical trials on the management of knee chondral
      defects. METHODS: A literature search of PubMed/Medline, CINAHL (Cumulative Index
      to Nursing and Allied Health Literature), EMBASE, and the Cochrane Central
      Register of Controlled Trials was conducted in September 2010 and updated in
      August 2011 to identify all English-language, Level I evidence, prospective,
      randomized controlled trials published from 1996 to present. The keyword search
      included the following: "autologous chondrocyte," "cartilage graft," "cartilage
      repair," "chondroplasty," "microfracture," "mosaicplasty," and/or
      "osteochondral." Nonoperative studies, nonhuman studies, ex vivo studies, non
      knee studies, and/or studies with follow-up of less than 1 year were excluded. A
      systematic review was performed on all included studies, and limitations and/or
      biases were identified and quantitated. RESULTS: Of 15,311 citations, 33
      abstracts were reviewed and 11 prospective, randomized controlled trials were
      included. We identified 9 major limitations (subject age, subject prior surgery,
      subject duration of symptoms, lesion location, lesion size, lesion number,
      procedure selection, procedure standardization, and limited histologic analysis)
      and 7 common biases (selection, performance, transfer, nonresponder, detection,
      publication, and study design). CONCLUSIONS: Level I therapeutic studies
      investigating the surgical management of human knee cartilage defects have
      substantial identified biases and limitations. This review has limitations
      because other classifications of bias or limitation exist. Optimal management of
      cartilage defects is controversial, and future rigorous research methods could
      minimize common biases through strict study design and patient selection
      criteria, larger patient enrollment, more extended follow-up, and standardization
      of clinical treatment pathways. LEVEL OF EVIDENCE: Level I, systematic review of
      Level I studies.

PMID- 22626909
TI  - Is aortic bioprosthesis degeneration influenced by metabolic factors?

PMID- 22626910
TI  - Are poor health behaviours in anxious and depressed cardiac patients explained by
      sociodemographic factors?
AB  - INTRODUCTION: While there is evidence of poor health behaviours in anxious and
      depressed cardiac patients, it is possible that sociodemographic factors explain
      these associations. Few previous studies have adequately controlled for
      confounders. The present study investigated health behaviours in anxious and
      depressed cardiac patients, while accounting for sociodemographic confounders.
      METHOD: A consecutive sample of 275 patients admitted to hospital after acute
      myocardial infarction (32%) or for coronary bypass surgery (40%) or percutaneous
      coronary intervention (28%) was interviewed six weeks after hospital discharge.
      Anxiety and depression were assessed using the Hospital Anxiety and Depression
      Scale (HADS). Smoking, physical activity, alcohol intake and dietary fat intake
      were assessed by self-report. Backward stepwise logistic regression was used to
      identify the factors independently associated with anxiety and depression.
      RESULTS: In total, 41 patients (15.2%) were 'depressed' (HADS-D >=8) while 68
      (25.2%) were 'anxious' (HADS-A >=8). Depressed patients reported higher rates of
      smoking (chi2)= 4.47, p = 0.034), lower physical activity (F = 8.63, p < 0.004)
      and higher dietary fat intake (F = 7.22, p = 0.008) than non-depressed patients.
      Anxious patients reported higher smoking rates (chi2)= 5.70, p = 0.024) and
      dietary fat intake (F = 7.71, p = 0.006) than non-anxious patients. In
      multivariate analyses, an association with depression was retained for both diet
      and physical activity, and an association with anxiety was retained for diet. Low
      social support and younger age were significant confounders with depression and
      anxiety respectively. CONCLUSIONS: While the high smoking rates evidenced in
      anxious and depressed patients were explained by sociodemographic factors, their
      poor diet and low physical activity (depressed patients only) were independent of
      these factors. Given the impact of lifestyle modification on survival after a
      cardiac event, anxious and depressed patients should be a priority for cardiac
      rehabilitation and other secondary prevention programmes.

PMID- 22626911
TI  - Surfing the internet with a BCI mouse.
AB  - In this paper, we present a new web browser based on a two-dimensional (2D) brain
      computer interface (BCI) mouse, where our major concern is the selection of an
      intended target in a multi-target web page. A real-world web page may contain
      tens or even hundreds of targets, including hyperlinks, input elements, buttons,
      etc. In this case, a target filter designed in our system can be used to exclude
      most of those targets of no interest. Specifically, the user filters the targets
      of no interest out by inputting keywords with a P300-based speller, while keeps
      those containing the keywords. Such filtering largely facilitates the target
      selection task based on our BCI mouse. When there are only several targets in a
      web page (either an original sparse page or a target-filtered page), the user
      moves the mouse toward the target of interest using his/her
      electroencephalographic signal. The horizontal movement and vertical movement are
      controlled by motor imagery and P300 potential, respectively. If the mouse
      encounters a target of no interest, the user rejects it and continues to move the
      mouse. Otherwise the user selects the target and activates it. With the
      collaboration of the target filtering and a series of mouse movements and target
      selections/rejections, the user can select an intended target in a web page.
      Based on our browser system, common navigation functions, including history
      rolling forward and backward, hyperlink selection, page scrolling, text input,
      etc, are available. The system has been tested on seven subjects. Experimental
      results not only validated the efficacy of the proposed method, but also showed
      that free internet surfing with a BCI mouse is feasible.

PMID- 22626912
TI  - Preoperative cognitive dysfunction is related to adverse postoperative outcomes
      in the elderly.
AB  - BACKGROUND: Preoperative risk stratification is commonly performed by assessing
      end-organ function (such as cardiac and pulmonary) to define postoperative risk.
      Little is known about impaired preoperative cognition and outcomes. The purpose
      of this study was to evaluate the impact of baseline impaired cognition on
      postoperative outcomes in geriatric surgery patients. STUDY DESIGN: Subjects 65
      years and older undergoing a planned elective operation requiring postoperative
      ICU admission were recruited prospectively. Preoperative baseline cognition was
      assessed using the validated Mini-Cog test. Impaired cognition was defined as a
      Mini-Cog score of <= 3. Delirium was assessed using the Confusion Assessment
      Method-ICU by a trained research team. Adverse outcomes were defined using the
      Veterans Affairs Surgical Quality Improvement Program definitions. RESULTS: One
      hundred and eighty-six subjects were included, with a mean age of 73 +/- 6 years.
      Eighty-two subjects (44%) had baseline impaired cognition. The impaired cognition
      group had the following unadjusted outcomes: increased incidence of 1 or more
      postoperative complications (41% vs 24%; p = 0.011), higher incidence of delirium
      (78% vs 37%; p < 0.001), longer hospital stays (15 +/- 14 vs 9 +/- 9 days; p =
      0.001), higher rate of discharge institutionalization (42% vs 18%; p = 0.001),
      and higher 6-month mortality (13% vs 5%; p = 0.040). Adjusting for potential
      confounders determined by univariate analysis, logistic regression found impaired
      cognition was still associated with the occurrence of 1 or more postoperative
      complications (odds ratio = 2.401; 95% CI, 1.185-4.865; p = 0.015). Kaplan-Meier
      survival analysis revealed higher mortality in the impaired cognition group (log
      rank p = 0.008). CONCLUSIONS: Baseline cognitive impairment in older adults
      undergoing major elective operations is related to adverse postoperative outcomes
      including increased complications, length of stay, and long-term mortality.
      Improved understanding of baseline cognition and surgical outcomes can aid
      surgical decision making in older adults.

PMID- 22626913
TI  - Impact of compliance with the American College of Surgeons trauma center
      verification requirements on organ donation-related outcomes.
AB  - BACKGROUND: In order to maximize organ donation opportunities, the American
      College of Surgeons (ACS) requires verified trauma centers to have a relationship
      with an organ procurement organization (OPO), a policy for notification of the
      OPO, a process to review organ donation rates, and a protocol for declaring
      neurologic death. We hypothesized that meeting the ACS requirements will be
      associated with improved donation outcomes. STUDY DESIGN: Twenty-four ACS
      verified Level I and Level II trauma centers were surveyed for the following
      registry data points from 2004 to 2008: admissions, ICU admissions, patients with
      a head Abbreviated Injury Score >= 5, deaths, and organ donors. Centers were also
      queried for the presence of the ACS requirements as well as other process
      measures and characteristics. The main outcomes measure was the number of organ
      donors per center normalized for patient volume and injury severity. The
      relationship between center characteristics and outcomes was determined. RESULTS:
      Twenty-one centers (88%) completed the survey and referred 2,626 trauma patients
      to the OPO during the study period, 1,008 were eligible to donate, and 699 became
      organ donors. Compliance with the 4 ACS requirements was not associated with
      increased organ donation outcomes. However, having catastrophic brain injury
      guidelines (CBIGs) and the presence of a trauma surgeon on a donor council were
      associated with significantly more organ donors per 1,000 trauma admissions (6.3
      vs 4.2 and 6.0 vs 4.2, respectively, p < 0.05). CONCLUSIONS: Although the ACS
      trauma center organ donation-related requirements were not associated with
      improved organ donor outcomes, involvement of trauma surgeons on donor councils
      and CBIGs were and should be encouraged. Additionally, incorporation of
      quantitative organ donation measures into the verification process should be
      considered.

PMID- 22626914
TI  - John J Conley Lecture on Ethics and Philosophy. Health care reform: ethical
      foundations, policy, and law.

PMID- 22626915
TI  - Compliance with Centers for Disease Control and Prevention field triage
      guidelines in an established trauma system.
AB  - BACKGROUND: Regionalization of trauma care reduces mortality and has clear
      guidelines for transport to the highest level of trauma care. Whether prehospital
      providers follow the CDC triage algorithm remains to be determined. STUDY DESIGN:
      We performed a 5-year retrospective cohort analysis of linked data from
      Washington State's Central Region Trauma Registry (CRTR) and King County
      Emergency Medical Services (KCEMS). Patients were analyzed based on transport to
      their designated hospital, as determined by geocode mapping, or directly to the
      level I center (no level II center is available in this region). RESULTS: Of the
      12,106 patients in the study, 5,976 (49.4%) were transported directly to a level
      I center from the scene. Of the remaining 6,130 patients initially transported to
      level III to V centers, 5,024 (41.5%) remained in the respective level III to V
      centers and 1,106 (9.1%) were transferred to the level I center. Patients
      transported directly to a level I center were more likely to be male, younger,
      have a penetrating injury, lower scene Glasgow Coma Scale (GCS), lower scene
      blood pressure, and be more severely injured. Level I direct scene transport was
      significantly less likely for older patients. Compared with patients ages 18 to
      45, the adjusted odds ratio for direct transport to the level I center was 0.7
      (95% CI 0.59 to 0.83) for patients aged 46 to 55 years; 0.47 (95% CI 0.39 to
      0.57) for those 56 to 65 years; 0.28 (95% CI 0.23 to 0.34) for patients 66 to 80
      years; and 0.11 (95% CI 0.09 to 0.14) for those older than 81 years. CONCLUSIONS:
      Prehospital providers follow physiologic, anatomic, and mechanistic parameters in
      steps 1 to 3 of the CDC field triage guidelines. However, contrary to the special
      considerations guideline in step 4, older age was associated with transport to
      the lower level of trauma care in our region.

PMID- 22626916
TI  - Modulation of motor area activity during observation of unnatural body movements.
AB  - The mirror neuron system (MNS) is activated when observing the actions of others.
      However, it remains unclear whether the MNS responds more strongly to natural
      bodily actions in the observer's motor repertoire than to unnatural actions. We
      investigated whether MNS activity is modulated by the unnaturalness of an
      observed action by inserting short pauses in the middle of the action (0, 2, and
      6 pauses; no-pause, pause-1, and pause-2 conditions, respectively). The results
      indicated that the number of pauses significantly affected motor area activity.
      Subsequent analyses revealed significant differences between the pause-1 and
      pause-2 conditions (P<0.01), as well as the no-pause and pause-2 conditions
      (P<0.05). There was significant activation in the pause-1 condition (P<0.001),
      while significant deactivation was observed in the pause-2 condition (P<0.05).
      These results indicate that MNS activity is modulated by the kinematic
      characteristics of the observed action. We suggest the possibility that a
      slightly deviated action may enhance the MNS activity during action observation,
      while a highly unnatural action would lead to a strong attenuation (deactivation)
      of activity in the MNS.

PMID- 22626917
TI  - Hemispheric asymmetries in the activation and monitoring of memory errors.
AB  - Previous research on the lateralization of memory errors suggests that the right
      hemisphere's tendency to produce more memory errors than the left hemisphere
      reflects hemispheric differences in semantic activation. However, all prior
      research that has examined the lateralization of memory errors has used self
      paced recognition judgments. Because activation occurs early in memory retrieval,
      with more time to make a decision, other memory processes, like strategic
      monitoring processes, may affect memory errors. By manipulating the time subjects
      were given to make memory decisions, this study separated the influence of
      automatic memory processes (activation) from strategic memory processes
      (monitoring) on the production of false memories. The results indicated that when
      retrieval was fast, the right hemisphere produced more memory errors than the
      left hemisphere. However, when retrieval was slow, the left hemisphere's error
      proneness increased compared to the fast retrieval condition, while the right
      hemisphere's error-proneness remained the same. These results suggest that the
      right hemisphere's errors are largely due to activation, while the left
      hemisphere's errors are influenced by both activation and monitoring.

PMID- 22626918
TI  - The amygdala is involved in affective priming effect for fearful faces.
AB  - The object of this study was to investigate whether the amygdala is involved in
      affective priming effect after stimuli are encoded unconsciously and consciously.
      During the encoding phase, each masked face (fearful or neutral) was presented to
      participants six times for 17ms each, using a backward masking paradigm. During
      the retrieval phase, participants made a fearful/neutral judgment for each face.
      Half of the faces had the same valence as that seen during encoding (congruent
      condition) and the other half did not (incongruent condition). Participants were
      divided into unaware and aware groups based on their subjective and objective
      awareness assessments. The fMRI results showed that during encoding, the amygdala
      elicited stronger activation for fearful faces than neutral faces but differed in
      the hemisphere according to the awareness level. During retrieval, the amygdala
      showed a significant repetition priming effect, with the congruent faces
      producing less activation than the incongruent faces, especially for fearful
      faces. These data suggest that the amygdala is important in unconscious
      retrieving of memories for emotional faces whether they are encoded consciously
      or unconsciously.

PMID- 22626919
TI  - Experts in fast-ball sports reduce anticipation timing cost by developing
      inhibitory control.
AB  - The present study was conducted to examine the relationship between expertise in
      movement correction and rate of movement reprogramming within limited time
      periods, and to clarify the specific cognitive processes regarding superior
      reprogramming ability in experts. Event-related potentials (ERPs) were recorded
      in baseball experts (n=7) and novices (n=7) while they completed a predictive
      task. The task was to manually press a button to coincide with the arrival of a
      moving target. The target moved at a constant velocity, and its velocity was
      suddenly decreased in some trials. Under changed velocity conditions, the
      baseball experts showed significantly smaller timing errors and a higher rate of
      timing reprogramming than the novices. Moreover, ERPs in baseball experts
      revealed faster central negative deflection and augmented frontal positive
      deflection at 200ms (N200) and 300ms (Pd300) after target deceleration,
      respectively. Following this, peak latency of the next positive component in the
      central region (P300b) was delayed. The negative deflection at 200ms, augmented
      frontal positive deflection, and late positive deflection at 300ms have been
      interpreted as reflecting stimulus detection, motor inhibition, and stimulus
      response translation processes. Taken together, these findings suggest that the
      experts have developed movement reprogramming to avoid anticipation cost, and
      this is characterized by quick detection of target velocity change, stronger
      inhibition of the planned, incorrect response, and update of the stimulus
      response relationship in the changed environment.

PMID- 22626920
TI  - Neural adaptation across viewpoint and exemplar in fusiform cortex.
AB  - The visual system has the remarkable ability to generalize across different
      viewpoints and exemplars to recognize abstract categories of objects, and to
      discriminate between different viewpoints and exemplars to recognize specific
      instances of particular objects. Behavioral experiments indicate the critical
      role of the right hemisphere in specific-viewpoint and -exemplar visual form
      processing and the left hemisphere in abstract-viewpoint and -exemplar visual
      form processing. Neuroimaging studies indicate the role of fusiform cortex in
      these processes, however results conflict in their support of the behavioral
      findings. We investigated this inconsistency in the present study by examining
      adaptation across viewpoint and exemplar changes in the functionally defined
      fusiform face area (FFA) and in fusiform regions exhibiting adaptation. Subjects
      were adapted to particular views of common objects and then tested with objects
      appearing in four critical conditions: same-exemplar, same-viewpoint adapted,
      same-exemplar, different-viewpoint adapted, different-exemplar adapted, and not
      adapted. In line with previous results, the FFA demonstrated a release from
      neural adaptation for repeated different viewpoints and exemplars of an object.
      In contrast to previous work, a (non-FFA) right medial fusiform area also
      demonstrated a release from neural adaptation for repeated different viewpoints
      and exemplars of an object. Finally, a left lateral fusiform area demonstrated
      neural adaptation for repeated different viewpoints, but not exemplars, of an
      object. Test-phase task demands did not affect adaptation in these regions.
      Together, results suggest that dissociable neural subsystems in fusiform cortex
      support the specific identification of a particular object and the abstract
      recognition of that object observed from a different viewpoint. In addition,
      results suggest that areas within fusiform cortex do not support abstract
      recognition of different exemplars of objects within a category.

PMID- 22626921
TI  - Surface EEG shows that functional segregation via phase coupling contributes to
      the neural substrate of mental calculations.
AB  - Multichannel EEG traces from healthy subjects are used to investigate the brain's
      self-organisation tendencies during two different mental arithmetic tasks. By
      making a comparison with a control-state in the form of a classification problem,
      we can detect and quantify the changes in coordinated brain activity in terms of
      functional connectivity. The interactions are quantified at the level of EEG
      sensors through descriptors that differ over the nature of functional
      dependencies sought (linear vs. nonlinear) and over the specific form of the
      measures employed (amplitude/phase covariation). Functional connectivity graphs
      (FCGs) are analysed with a novel clustering algorithm, and the resulting
      segregations enter an appropriate discriminant function. The magnitude of the
      contrast function depends on the frequency-band (theta, alpha(1), alpha(2), beta
      and gamma) and the neural synchrony descriptor. We first show that the maximal
      contrast corresponds to a phase coupling descriptor and then identify the
      corresponding spatial patterns that represent best the task-induced changes for
      each frequency band. The principal finding of this study is that, during mental
      calculations, phase synchrony plays a crucial role in the segregation into
      distinct functional domains, and this segregation is the most prominent feature
      of the brain's self-organisation as this is reflected in sensor space.

PMID- 22626922
TI  - Synthesis, characterization and thermodynamics of complex formation of some new
      Schiff base ligands with some transition metal ions and the adduct formation of
      zinc Schiff base complexes with some organotin chlorides.
AB  - Four new complexes, [M(Salpyr)] where Salpyr=N,N'-bis(Salicylidene)-2,3- and 3,4
      diiminopyridine and M=Co, Cu, Mn, Ni and Zn were synthesized and characterized by
      (1)H NMR, IR spectroscopy, elemental analysis and UV-vis spectrophotometry. UV
      vis spectrophotometric study of the adduct formation of the zinc(II) complexes,
      [Zn(2,3-Salpyr)] and [Zn(3,4-Salpyr)], as donor with R(2)SnCl(2) (R=methyl,
      phenyl, n-butyl), PhSnCl(3) and Bu(3)SnCl as acceptors has been investigated in
      methanol, as solvent. The formation constants and the thermodynamic free energies
      were measured using UV-vis spectrophotometry. Titration of the organotin
      chlorides with Zn(II) complexes at various temperatures (T=283-313K) leads to 1:1
      adduct formation. The results show that the formation constants were decreased by
      increasing the temperature. The trend of the reaction of R(n)SnCl(4-n) as
      acceptors toward given zinc complexes was as follows: PhSnCl3 > Me2SnCl2 >
      Ph2SnCl2 > Bu2SnCl2 > Bu3SnCl. By considering the formation constants and the
      DeltaG degrees  of the complex formation for the Schiff base as donor and the
      M(II) as acceptor, the following conclusion was drawn: the formation constant for
      a given Schiff base changes according to the following trend: Ni > Cu > Co > Zn >
      Mn.

PMID- 22626923
TI  - The genus Commiphora: a review of its traditional uses, phytochemistry and
      pharmacology.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The resinous exudates of the Commiphora species,
      known as 'myrrh', are used in traditional Chinese medicine for the treatment of
      trauma, arthritis, fractures and diseases caused by blood stagnation. Myrrh has
      also been used in the Ayurvedic medical system because of its therapeutic effects
      against inflammatory diseases, coronary artery diseases, gynecological disease,
      obesity, etc. AIM OF THE REVIEW: Based on a comprehensive review of traditional
      uses, phytochemistry, pharmacological and toxicological data on the genus
      Commiphora, opportunities for the future research and development as well as the
      genus' therapeutic potential are analyzed. METHODS: Information on the Commiphora
      species was collected via electronic search (using Pubmed, SciFinder, Scirus,
      Google Scholar and Web of Science) and a library search for articles published in
      peer-reviewed journals. Furthermore, information also was obtained from some
      local books on ethnopharmacology. This paper covers the literature, primarily
      pharmacological, from 2000 to the end of December 2011. RESULTS: The resinous
      exudates from the bark of plants of the genus Commiphora are important indigenous
      medicines, and have a long medicinal application for arthritis, hyperlipidemia,
      pain, wounds, fractures, blood stagnation, in Ayurvedic medicine, traditional
      Chinese medicine and other indigenous medical systems. Phytochemical
      investigation of this genus has resulted in identification of more than 300
      secondary metabolites. The isolated metabolites and crude extract have exhibited
      a wide of in vitro and in vivo pharmacological effects, including
      antiproliferative, antioxidant, anti-inflammatory and antimicrobial. The
      bioactive steroids guggulsterones have attracted most attention for their potent
      hypolipidemic effect targeting farnesoid X receptor, as well as their potent
      inhibitory effects on tumor cells and anti-inflammatory efficiency. CONCLUSIONS:
      The resins of Commiphora species have emerged as a good source of the traditional
      medicines for the treatment of inflammation, arthritis, obesity, microbial
      infection, wound, pain, fractures, tumor and gastrointestinal diseases. The resin
      of C. mukul in India and that of C. molmol in Egypt have been developed as anti
      hyperlipidemia and antischistosomal agents. Pharmacological results have
      validated the use of this genus in the traditional medicines. Some bioassays are
      difficult to reproduce because the plant materials used have not been well
      identified, therefore analytical protocol and standardization of extracts should
      be established prior to biological evaluation. Stem, bark and leaf of this genus
      should receive more attention. Expansion of research materials would provide more
      opportunities for the discovery of new bioactive principles from the genus
      Commiphora.

PMID- 22626924
TI  - Effect of Viscum articulatum Burm. (Loranthaceae) in Nomega-nitro-L-arginine
      methyl ester induced hypertension and renal dysfunction.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Viscum articulatum Burm. is used traditionally in
      Chinese medicine for treating hypertension. AIM OF THE STUDY: The present study
      was designed to evaluate the antihypertensive activity of the methanolic extract
      of Viscum articulatum (MVA) against N(omega)-nitro-L-arginine methyl ester (L
      NAME) induced hypertension in rats. MATERIALS AND METHODS: Six groups of rats
      were investigated for 4 weeks as normal control, L-NAME (40 mg/kg/day), L
      NAME+enalapril (15 mg/kg/day), L-NAME+L-arginine (100 mg/kg/day), L-NAME+MVA (200
      mg/kg/day) and L-NAME+MVA (400 mg/kg/day) for four weeks. The systolic blood
      pressure (SBP) and heart rate (HR) were measured weekly throughout the
      experimental period. The urine electrolytes concentration, cardiac mass index,
      serum nitrate/nitrite (NO(x)) level, serum creatinine level and lipid profile
      were determined. RESULTS: Treatment with MVA (200 and 400 mg/kg) or enalapril
      delayed the rise in SBP produced by administration of L-NAME. None of the
      treatments had a significant effect on the depression of the serum NO(x) level
      caused by L-NAME. The serum creatinine and total cholesterol concentrations were
      elevated upon administration of L-NAME, and this elevation was prevented by MVA
      co-administration. The urine volume and urine potassium ion level were depressed
      by L-NAME administration and this effect being inhibited in MVA and enalapril
      groups. There was no cardiac hypertrophy and HR change after 28 day of L-NAME
      administration. CONCLUSION: We conclude that MVA may have an antihypertensive
      effect in the NO deficient type of hypertension, which may be attributed to its
      diuretic, nephroprotective and hypolipidemic actions.

PMID- 22626925
TI  - Berberine acutely inhibits the digestion of maltose in the intestine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese Goldthread Rhizome has been used in
      the Traditional Chinese Medicine as an important ingredient of many formulas for
      the treatment of diabetes mellitus. Berberine, the main effective composition of
      Chinese Goldthread Rhizome, is also effective in treating diabetes in today's
      clinical practice of Traditional Chinese Medicine. AIM OF THE STUDY: To evaluate
      the hypoglycemic activity of berberine which treats acutely on the postprandial
      blood glucose, and to explore the mechanism of this activity. MATERIALS AND
      METHODS: 1. One-dose preprandial intragastric administrations of berberine were
      given to normal animals (dogs and rats), and the postprandial blood glucose
      concentration curves were measured. Serum insulin enzyme linked immunosorbent
      assay (ELISA) was only performed in rats. 2. The euglycemic clamp test was
      performed to evaluate the effect of one-dose berberine intragastric
      administration on the blood glucose transformation and utilization rate in rats.
      3. In the Caco-2 cell monolayer test, the changes of glucose concentration on the
      apical and basolateral sides were measured when the maltose solution containing
      berberine was added to the apical side. 4. The inhibition ratio of berberine
      against alpha-glucosidase was measured in vitro. 5. The effect of berberine on
      the fluorescence emission spectrums of alpha-glucosidase was studied. RESULTS:
      One-dose preprandial intragastric administration of berberine delayed the rise of
      post-maltose blood glucose, did not affect postprandial blood glucose after
      glucose meal, and did not affect the insulin level in normal rats; reduced post
      maltose blood glucose in normal dogs. 2. The result of euglycemic clamp test
      showed that one-dose intragastric administration of berberine had no effect on
      the blood glucose transformation and utilization rate in rats. 3. Berberine added
      to the maltose solution on the apical side of Caco-2 cell monolayer reduced the
      glucose concentration on the apical side. Glucose in basolateral side of all
      groups cannot be detected. 4. Berberine inhibited the activity of alpha
      glucosidase in vitro. 5. Berberine significantly and concentration dependently
      quenched the fluorescence emission spectrum of alpha-glucosidase. CONCLUSION: Our
      findings suggest an additional mechanism of the hypoglycemic activity of
      berberine by demonstrating its ability to acutely inhibit the alpha-glucosidase,
      and support the traditional use of berberine and Chinese Goldthread Rhizome for
      the treatment of diabetes mellitus.

PMID- 22626926
TI  - Anti-proliferative activities on HeLa cancer cell line of Thai medicinal plant
      recipes selected from MANOSROI II database.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Thai/Lanna medicinal plant recipe database
      "MANOSROI II" contained the medicinal plant recipes of all regions in Thailand
      for the treatment of various diseases including anti-cancer medicinal plant
      recipes. AIM OF THE STUDY: To investigate anti-proliferative activity on HeLa
      cell lines of medicinal plant recipes selected from the Thai/Lanna medicinal
      plant recipe database "MANOSROI II". MATERIALS AND METHODS: The forty aqueous
      extracts of Thai/Lanna medicinal plant recipes selected from the Thai/Lanna
      medicinal plant recipe database "MANOSROI II" were investigated for anti
      proliferative activity on HeLa cell line by SRB assay. The apoptosis induction by
      caspase-3 activity and MMP-2 inhibition activity by zymography on HeLa cell line
      of the three selected aqueous extracts, which gave the highest anti-proliferative
      activity were determined. Phytochemicals and anti-oxidative activities including
      free radical scavenging activity, inhibition of lipid peroxidation and metal
      chelating inhibition activities were also investigated. RESULT: Sixty percentages
      of the medicinal plant recipes selected from "MANOSROI II" database showed anti
      proliferative activity on HeLa cell line. The recipes of N031(Albizia chinensis
      (Osbeck) Merr, Cassia fistula L., and Dargea volubilis Benth.ex Hook. etc.), N039
      (Nymphoides indica L., Peltophorum pterocarpum (DC.), and Polyalthia debilis
      Finet et Gagnep etc.) and N040 (Nymphoides indica L. Kuntze, Sida rhombifolia L.,
      and Xylinbaria minutiflora Pierre. etc.) gave higher anti-proliferative activity
      than the standard anti-cancer drug, cisplatin of 1.25, 1.29 and 30.18 times,
      respectively. The positive relationship between the anti-proliferative activity
      and the MMP-2 inhibition activity and metal chelating inhibition activity was
      observed, but no relationship between the anti-proliferative activity and
      apoptosis induction, free radical scavenging activity and lipid peroxidation
      inhibition activity. Phytochemicals found in these extracts were alkaloids,
      flavonoids, tannins and xanthones, but not anthraquinones and carotenoids. The
      recipe N040 exhibited the highest anti-proliferative and MMP-2 inhibition on HeLa
      cancer cell line at 30 and threefolds of cisplatin, respectively (p<0.05), while
      recipe N031 gave the highest caspase-3 activity (1.29-folds over the control)
      (p<0.05). CONCLUSION: This study has demonstrated that recipe N040 selected from
      MANOSROI II database appeared to be a good candidate with high potential for the
      further development as an anti-cancer agent.

PMID- 22626927
TI  - Beneficial effects of the ethanol extract of Caesalpinia pyramidalis on the
      inflammatory response and abdominal hyperalgesia in rats with acute pancreatitis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia pyramidalis Tul. (Fabaceae) is a
      plant found in the Northeast of Brazil that is popularly used to treat
      inflammation. Acute pancreatitis (AP) is an inflammatory disease for which
      abdominal pain is a relevant symptom. As there is no specific therapy for AP, we
      investigated the effect of the ethanol extract from the inner bark of C.
      pyramidalis (EECp) on the AP induced by common bile duct obstruction (CBDO) in
      rats. MATERIAL AND METHODS: AP was induced in male Wistar rats (200-250 g, n=6-8)
      through laparotomy and subsequent CBDO. Animals were euthanized after 6 (G6h) or
      24 h (G24h) of induction. In the G6h protocol, animals were pretreated with EECp
      (100-400 mg/kg, p.o.) or vehicle (Tween 80; 0.2%) 1h before CBDO or sham surgery.
      For the G24h protocol, rats were pretreated with EECp (400mg/kg, 1h before CBDO
      or 1 h before and 12 h after CBDO) or vehicle. The following parameters were
      measured: inflammatory/oxidative (myeloperoxidase activity and malondialdehyde
      formation in the pancreas and lung, leukocyte counts in the blood and serum
      nitrate/nitrite), enzymatic (serum amylase and lipase levels) and nociceptive
      (abdominal hyperalgesia). RESULTS: Induction of AP by CBDO significantly
      increased all the parameters evaluated in both G6h and G24h protocols when
      compared with the respective sham group. In the G6h protocol, the EECp
      pretreatment (400 mg/kg) significantly reduced all these parameters, besides
      completely inhibiting abdominal hyperalgesia. The same profile of reduction was
      observed from two administrations of EECp in the G24h protocol, while one single
      dose of EECp was able to significantly reduce pancreatic MDA, serum lipase
      levels, leukocyte counts in the blood and abdominal hyperalgesia without
      affecting the other parameters in the G24h protocol. Furthermore, rutin was found
      in the EECp. CONCLUSIONS: Our results demonstrated that EECp decreases
      inflammation, lipoperoxidation and hyperalgesia in CBDO-induced AP, making it of
      interest in future approaches to treat this condition.

PMID- 22626928
TI  - Number of tracts or stone size: which influences outcome of percutaneous
      nephrolithotomy for staghorn renal stones?.
AB  - INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is the recommended first-line
      treatment for staghorn stones. To achieve complete stone clearance, PCNL may
      require using multiple tracts. OBJECTIVE: To evaluate outcome of PCNL in patients
      with staghorn calculi and its correlation with the number of tracts and stone
      features. MATERIALS AND METHODS: One hundred consecutive patients with staghorn
      renal stone who underwent PCNL were included in the study. Perioperative and
      postoperative features were recorded. Correlation of the variables with number of
      tracts and stone size was assessed. RESULTS: Mean age (+/- SD) was 49.6 +/- 14.7
      years. Our patients were ASA class I. The mean cumulative stone burden was 365.9
      +/- 156.5 mm(2). The mean number of tracts was 2.4 (range: 1-7), and stone-free
      rate was 83%. The stone-free rate (p = 0.026) and hospital stay (p = 0.005)
      correlated with stone size, but not with number of tracts. Postoperative fever
      correlated with stone size (p = 0.017) and number of tracts (p = 0.037).
      CONCLUSION: PCNL using multiple tracts seem to be effective and safe in treatment
      of staghorn calculi. Most outcome measures correlated with stone size rather than
      number of tracts.

PMID- 22626929
TI  - Novel AAV-based genetic vaccines encoding truncated dengue virus envelope
      proteins elicit humoral immune responses in mice.
AB  - The envelope protein of dengue virus is involved in host cell attachment for
      entry and induction of protective immunity. Current efforts are focused on
      producing a tetravalent vaccine by mixing four monovalent vaccine components. In
      this work, we developed a genetic vaccine based on a novel adeno-associated viral
      (AAV) vector expressing the carboxy-terminal truncated envelope protein (79E) of
      dengue virus. The expression of the recombinant 79E protein in HEK 293 cells was
      confirmed by Western blot. Vectors packaged with novel AAV capsids (AAV2/8 or
      AAV2/rh32.33) were injected into C57BL/6 mice intramuscularly. Dengue virus
      antigen was produced in the mice and induced long-lasting antibody responses
      against the dengue virus still detectable 20 weeks after immunization. AAV2/8
      vaccine induced higher anti-dengue virus antibody levels than AAV2/rh32.33
      vaccine or AAV plasmid. Furthermore, the anti-dengue antibodies could neutralize
      homogeneous dengue virus. These results demonstrated that the AAV vaccines
      possessed appropriate immunogenicity and could be used for the development of an
      effective dengue vaccine.

PMID- 22626930
TI  - Evasion from NK cell-mediated immune responses by HIV-1.
AB  - Human immunodeficiency virus type 1 (HIV-1) mostly owes its success to its
      ability to evade host immune responses. Understanding viral immune escape
      mechanisms is a prerequisite to improve future HIV-1 vaccine design. This review
      focuses on the strategies that HIV-1 has evolved to evade recognition by natural
      killer (NK) cells.

PMID- 22626932
TI  - Bio-inspired nanopore-based sensors: Comment on "Nanopores: A journey towards DNA
      sequencing" by M. Wanunu.

PMID- 22626931
TI  - Exploring the Plasmodium falciparum cyclic-adenosine monophosphate (cAMP)
      dependent protein kinase (PfPKA) as a therapeutic target.
AB  - One of the prototype mammalian kinases is PKA and various roles have been defined
      for PKA in malaria pathogenesis. The recently described phospho-proteomes of
      Plasmodium falciparum introduced a great volume of phospho-peptide data for both
      basic research and identification of new anti-malaria therapeutic targets. We
      discuss the importance of phosphorylations detected in vivo at different sites in
      the parasite R and C subunits of PKA and highlight the inhibitor sites in the
      parasite R subunit. The N-terminus of the parasite R subunit is predicted to be
      very flexible and we propose that phosphorylation at multiple sites in this
      region likely represent docking sites for interactions with other proteins, such
      as 14-3-3. The most significant observation when the P. falciparum C subunit is
      compared to mammalian C isoforms is lack of phosphorylation at a key site tail
      implying that parasite kinase activity is not regulated so tightly as mammalian
      PKA. Phosphorylation at sites in the activation loop could be mediating a number
      of processes from regulating parasite kinase activity, to mediating docking of
      other proteins. The important differences between Plasmodium and mammalian PKA
      isoforms that indicate the parasite kinase is a valid anti-malaria therapeutic
      target.

PMID- 22626933
TI  - The richness of the eye of a needle: Comment on "Nanopores: A journey towards DNA
      sequencing" by M. Wanunu.

PMID- 22626934
TI  - Interaction between lexical and grammatical language systems in the brain.
AB  - This review concentrates on two different language dimensions: lexical/semantic
      and grammatical. This distinction between a lexical/semantic system and a
      grammatical system is well known in linguistics, but in cognitive neurosciences
      it has been obscured by the assumption that there are several forms of language
      disturbances associated with focal brain damage and hence language includes a
      diversity of functions (phoneme discrimination, lexical memory, grammar,
      repetition, language initiation ability, etc.), each one associated with the
      activity of a specific brain area. The clinical observation of patients with
      cerebral pathology shows that there are indeed only two different forms of
      language disturbances (disturbances in the lexical/semantic system and
      disturbances in the grammatical system); these two language dimensions are
      supported by different brain areas (temporal and frontal) in the left hemisphere.
      Furthermore, these two aspects of the language are developed at different ages
      during child's language acquisition, and they probably appeared at different
      historical moments during human evolution. Mechanisms of learning are different
      for both language systems: whereas the lexical/semantic knowledge is based in a
      declarative memory, grammatical knowledge corresponds to a procedural type of
      memory. Recognizing these two language dimensions can be crucial in understanding
      language evolution and human cognition.

PMID- 22626935
TI  - DNA nanopore sequencing within the technology landscape: Comment on "Nanopores: A
      journey towards DNA sequencing" by M. Wanunu.

PMID- 22626936
TI  - A nice theory has probably more to do with aesthetics than reality: Comment on
      "Interaction between lexical and grammatical language systems in the brain" by
      Alfredo Ardila.

PMID- 22626937
TI  - Nanopores - mission accomplished and what next?: Comment on "Nanopores: A journey
      towards DNA sequencing" by M. Wanunu.

PMID- 22626938
TI  - The impact of missense mutations on human behavior.

PMID- 22626940
TI  - Image guided therapy: the advent of theranostic agents.
AB  - Theranostic agents represent a recently introduced class of imaging probes
      designed to offer to pharmacologists and physicians a robust tool for minimally
      invasive in vivo visualization of drug delivery/release and therapy monitoring.
      By means of these agents, novel strategies able to integrate diagnosis and
      therapy could be developed. This highly interdisciplinary research field is one
      of the more innovative products resulting from the synergism between molecular
      imaging and nanomedicine. Potential applications of theranosis include the in
      vivo assessment of drug biodistribution and accumulation at the target site,
      visualization of the drug release from a given nanocarrier, and real-time
      monitoring of the therapeutic outcome. The expected end-point of theranostic
      agents is to provide a fundamental support for the optimization of innovative
      diagnostic and therapeutic strategies that could contribute to emerging concepts
      in the field of the "personalized medicine". This perspective paper aims at
      providing the reader the basic principles of theranosis with a particular
      emphasis to the design of theranostic agents.

PMID- 22626941
TI  - Modeling the oral cavity: in vitro and in vivo evaluations of buccal drug
      delivery systems.
AB  - The delivery of drugs through the buccal mucosa has attracted much research
      interest over the past two decades and numerous approaches, both conventional and
      complex, have been developed in an attempt to deliver a variety of pharmaceutical
      compounds via the buccal route. However, the design of appropriate in vitro and
      in vivo methods to evaluate the behavior of these delivery systems is often
      ignored. This review aims to outline the progress in the in vitro and in vivo
      modeling of buccal drug delivery and provide a critical review of currently used
      methods. The development of a range of in vitro methods is outlined including
      disintegration/dissolution testing, in vitro mucoadhesion tests, in vitro
      residence time evaluation and permeability studies. The suitability of commonly
      used animal models for in vivo evaluation is also discussed and the physiological
      comparison of the animal oral cavity with that of a human's is described.

PMID- 22626939
TI  - Biodistribution and inflammatory profiles of novel penton and hexon double-mutant
      serotype 5 adenoviruses.
AB  - The use of adenovirus serotype 5 (Ad5) vectors in the clinical setting is
      severely hampered by the profound liver tropism observed after intravascular
      delivery coupled with the pronounced inflammatory and innate immune response
      elicited by these vectors. Liver transduction by circulating Ad5 virions is
      mediated by a high-affinity interaction between the capsid hexon protein and
      blood coagulation factor X (FX), whilst penton-alpha(v)integrin interactions are
      thought to contribute to the induction of anti-Ad5 inflammatory and innate immune
      responses. To overcome these limitations, we sought to develop and characterise
      for the first time novel Ad5 vectors possessing mutations ablating both hexon:FX
      and penton:integrin interactions. As expected, intravascular administration of
      the FX binding-ablated Ad5HVR5*HVR7*E451Q vector (AdT*) resulted in significantly
      reduced liver transduction in vivo compared to Ad5. In macrophage-depleted mice,
      increased spleen uptake of AdT* was accompanied by an elevation in the levels of
      several inflammatory mediators. However ablation of the penton RGD motif in the
      AdT* vector background (AdT*RGE) resulted in a significant 5-fold reduction in
      spleen uptake and attenuated the antiviral inflammatory response. A reduction in
      spleen uptake and inflammatory activation was also observed in animals after
      intravascular administration of Ad5RGE compared to the parental Ad5 vector, with
      reduced co-localisation of the viral beta-galactosidase transgene with MAdCAM-1+
      sinus-lining endothelial cells. Our detailed assessment of these novel
      adenoviruses indicates that penton base RGE mutation in combination with FX
      binding-ablation may be a viable strategy to attenuate the undesired liver uptake
      and pro-inflammatory responses to Ad5 vectors after intravascular delivery.

PMID- 22626942
TI  - Comparison of patient rated treatment response with measured improvement in
      Parkinson's disease.
AB  - BACKGROUND: A marked response to dopamine replacement therapy is important in
      supporting a diagnosis of idiopathic Parkinson's disease (PD). The aim of the
      study was to compare PD patients' subjective rating of improvement with measured
      improvement on a number of scales. METHODS: People with clinically defined PD
      were identified from a prospective long term follow-up study of incident
      parkinsonian patients. Changes in the Unified Parkinson's Disease Rating Scale
      (UPDRS) (activities of daily living and motor subsections), timed tests and
      Parkinson's Disease Questionnaire, full version, between assessments immediately
      before starting adequate dopamine replacement and the two subsequent follow-up
      assessments (mean 6 and 12 months after baseline) were calculated. These were
      compared with the patients' own subjective ratings of improvement (nil, slight,
      moderate, good, excellent). RESULTS: 133 patients were included (mean age 71
      years, 56% men). Thirty-eight patients were treated with a dopamine agonist and
      95 with l-dopa (median l-dopa equivalent dose 300 mg). Most patients showed
      improvements in their measured scores but there was no statistically significant
      association between these scores and the patient subjective response, except for
      the motor UPDRS at the first follow-up. A third of those who showed no
      improvement in their motor UPDRS at the first follow-up rated their improvement
      as moderate or better, while 29% of those whose motor UPDRS improved by over 50%
      said they had no or slight improvement. CONCLUSION: PD patients' subjective
      ratings of their degree of improvement often do not accurately reflect the degree
      of objective change in parkinsonian impairment or disability. Clinicians should
      record a simple measure of motor impairment before and after treatment to assess
      treatment response more accurately.

PMID- 22626943
TI  - Cognition and psychopathology in myoclonus-dystonia.
AB  - OBJECTIVE: (1) To study the neuropsychological and psychopathological profile in
      myoclonus-dystonia (M-D) patients with and without a mutation in the DYT11 gene.
      (2) To explore whether cognitive and psychiatric impairments are related to
      severity and duration of motor symptoms. Herewith, this study may help to clarify
      whether neuropsychological and psychiatric symptoms are associated with the DYT11
      mutation or are secondary to the burden of motor impairments that originated in
      early childhood. METHODS: Extensive batteries of neuropsychological tests and
      psychiatric questionnaires were administered to DYT11 gene mutation-carrying (MC)
      M-D patients (n=31), non-mutation-carrying (NMC) M-D patients (n=20) and a
      healthy control group (n=36). RESULTS: MC M-D patients demonstrated mild
      impairments in executive functions. On the contrary, with the exception of one
      type of verbal fluency, no evident cognitive impairments were found in NMC M-D
      patients. Further, increased rates of anxiety disorders were found only in MC M-D
      patients, whereas increased rates of depressive symptoms were observed in both M
      D groups. Correlation analyses yielded modest associations between severity of
      myoclonus and executive functions. No relationships were found between
      neuropsychological test performance and scores on the psychiatric assessments.
      CONCLUSIONS: The findings of this study suggest that anxiety disorders and
      executive dysfunctions may be part of the phenotype of M-D patients with a DYT11
      mutation, whereas depressive symptoms and semantic fluency impairments may be
      secondary to suffering from a chronic movement disorder, regardless of DYT11 gene
      mutation.

PMID- 22626944
TI  - Reduced R2' in multiple sclerosis normal appearing white matter and lesions may
      reflect decreased myelin and iron content.
AB  - BACKGROUND: R(2)' is an MRI measure of microscopic magnetic field inhomogeneity,
      and is increased by the paramagnetic effect of iron and the diamagnetic effect of
      myelin. R(2)' may detect features of multiple sclerosis (MS) not evident with
      conventional MRI. METHODS: Multiecho T(2) and T(2)* weighted sequences were
      obtained from 21 healthy controls (nine men, 12 women; mean age 36 years) and 28
      MS patients (seven men, 21 women; 18 relapsing remitting, 10 secondary
      progressive; mean age 42 years). T(2) and T(2)* relaxation time maps were created
      from the multiecho sequences, and R(2)' maps were created using the formula R(2)'
      = R(2)*-R(2) = 1/T(2)*-1/T(2). R(2)' was measured in MS white matter lesions and
      in regions of interest in normal appearing white matter (NAWM) and grey matter in
      all subjects. RESULTS: R(2)' was reduced in NAWM in MS compared with controls
      (9.5/s vs 10.1/s, p=0.05). R(2)' was additionally reduced in lesions, both T(1)
      isointense (8.5/s vs 9.5/s, p=0.02) and T(1) hypointense (7.7/s vs 9.5/s,
      p=0.003) compared with NAWM. R(2)' tended to be higher in the basal ganglia of MS
      patients compared with controls, and was significantly higher in the caudate
      nucleus in secondary progressive MS (12.9/s vs 10.9/s, p=0.03). Increased T(2)
      lesion volume predicted an increase in R(2)' in the caudate (beta=0.412, p=0.02).
      CONCLUSIONS: Reduction in R(2)' in NAWM and lesions is consistent with a
      decreases in myelin, tissue iron and/or deoxyhaemoglobin. Increased caudate R(2)'
      in patients with secondary progressive MS is consistent with increased iron
      deposition, as corroborated by other techniques.

PMID- 22626946
TI  - Term pregnancies and the clinical characteristics of multiple sclerosis: a
      population based study.
AB  - OBJECTIVE: Pregnancy has a well documented effect on relapse risk in multiple
      sclerosis (MS). Prospective studies have reported a significant decline by two
      thirds in the rate of relapses during the third trimester of pregnancy and a
      significant increase by two-thirds during the first 3 months postpartum. However,
      it is unclear as to whether there are any long term effects on disability.
      METHODS: Data were collated from clinical records and family histories
      systematically collected from the University of British Columbia MS Clinic.
      RESULTS: Clinical and term pregnancy data were available from 2105 female MS
      patients. MS patients having children after MS onset took the longest time to
      reach an Expanded Disability Status Scale (EDSS) score of 6 (mean 22.9 years) and
      patients having children before MS onset were the quickest (mean 13.2 years).
      However, these effects were not related to term pregnancy and were fully
      accounted for by age of MS onset. CONCLUSIONS: Pregnancy had no effect on the
      time to reach an EDSS score 6. As MS predominantly affects women of childbearing
      age, women with MS can be reassured that term pregnancies do not appear to have
      any long term effects on disability.

PMID- 22626945
TI  - Clonazepam quiets tinnitus: a randomised crossover study with Ginkgo biloba.
AB  - OBJECTIVE: To assess the effect of Ginkgo biloba and clonazepam, a gamma
      aminobutyric acid (GABA)-receptor agonist, upon tinnitus. METHODS: This was an
      open-label, randomised, crossover study. 27 men and 11 women (aged 16-80 (mean
      58)) with tinnitus for more than 2 months were enrolled. Participants were
      randomised to either clonazepam or G biloba for the first 3 weeks. For the next 2
      weeks of washout no medication was taken. For the final 3 weeks, subjects were
      given the other drug. The initial dose of clonazepam and G biloba was one tablet
      daily (clonazepam 0.5 mg; G biloba 40 mg). Subjects were instructed to increase
      the dose by one tablet every 3 days to a maximum of four tablets daily until they
      perceived a satisfactory decrease in tinnitus loudness or intolerable side
      effects. Tinnitus was assessed with pitch and loudness matching, tinnitus
      handicap inventory, and visual analogue scales of loudness, duration and
      annoyance. RESULTS: Comparing before and after each drug, clonazepam
      significantly improved tinnitus loudness (74% of subjects), duration (63%),
      annoyance (79%), and tinnitus handicap inventory score (61%), whereas the G
      biloba showed no significant differences on any of these measures. CONCLUSION:
      Clonazepam is effective in treating tinnitus; G biloba is ineffective.

PMID- 22626947
TI  - Utility of biomarkers and imaging in the development of drugs for the treatment
      of coronary atherosclerosis.
AB  - Biomarkers and imaging trials have often been used as guideposts in the
      development of drugs for atherosclerosis. This article explores the role of
      biomarkers and imaging trials in the development of 4 drugs: rimonabant,
      torcetrapib, ezetimibe, and niacin. Rimonabant, a selective cannabinoid-1
      receptor, causes weight loss and exerts favourable effects on lipid biomarkers.
      An intracoronary ultrasound study showed no effect for the primary but
      significant benefit for the secondary end point. A large clinical outcomes trial
      was halted when it became apparent that the drug caused serious psychiatric side
      effects, including suicide. Torcetrapib, a cholesteryl ester transfer protein
      inhibitor, lowers low-density lipoprotein (LDL) cholesterol and induces a marked
      increase in high-density lipoprotein (HDL) cholesterol. However, a large clinical
      outcomes trial was halted very prematurely due to a 58% increase in all-cause
      mortality. Neutral imaging studies were reported later. Ezetimibe lowers low
      density lipoprotein cholesterol but did not reduce carotid intima-media
      thickness, and there is as yet no clinical trial evidence that it reduces
      cardiovascular events after a decade on the market. Niacin exerts favourable
      effects on lipid biomarkers and has shown regression of atherosclerosis in small
      carotid imaging trials, but did not reduce events in a recent clinical trial that
      was stopped early due to a lack of efficacy. In summary, favourable effects on
      lipid biomarkers often do not translate into clinical benefit, and imaging
      trials, which focus on a narrow measurement of atherosclerosis, are also often
      not helpful.

PMID- 22626948
TI  - ADAMTS13 promotes angiogenesis and modulates VEGF-induced angiogenesis.
AB  - Plasma ADAMTS13 deficiency results in the clinical disorder thrombotic
      thrombocytopenic purpura. However, other potential pathophysiological roles of
      ADAMTS13 in endothelial cell biology remain unexplored. To assess the possible
      role of ADAMTS13 and its interactions with VEGF-mediated angiogenesis, the
      effects of ADAMTS13 on human umbilical vein endothelial cell (HUVEC) were studied
      in Matrigel tube formation, proliferation, cell migration, and scratch wound
      assays. Treatment of endothelial cells with exogenous recombinant full-length
      ADAMTS13 alone promoted angiogenesis in a dose-dependent manner. HUVEC incubated
      with 200 ng/mL ADAMTS13 (1.4 nM) resulted in a 65% increase in cell tube
      formation when compared to the EBM-2 control. HUVEC treated with 30 ng/mL
      ADAMTS13 (204.1 pM) resulted in an 83% increase in proliferation in a visual
      counting assay, whereas HUVEC treated with 10 ng/mL ADAMTS13 (68.0 pM) yielded a
      295% increase in EC migration in a Boyden chamber assay. In contrast, ADAMTS13
      inhibited VEGF-induced angiogenesis in a dose-dependent manner, with 200ng/mL
      inhibiting tube formation by 35%. HUVEC co-incubated with ADAMTS13 and an
      antibody to the ADAMTS13 thrombospondin domains 5-7 reversed the inhibition of
      tube formation. HUVEC treated with 30 ng/mL ADAMTS13 and 6.2 ng/mL (323.0 pM)
      VEGF proliferated 40% slower than the VEGF control after 24 h of incubation as
      measured by visual counting assay. Treatment of HUVEC with 6.2 ng/mL VEGF and 10
      ng/mL ADAMTS13 inhibited cell migration by 48%, compared to the VEGF control.
      Substitution of ADAMTS13 with truncated ADAMTS13 (deletion of C-terminal TSP1
      domain) did not significantly increase angiogenesis or suppress VEGF-induced
      angiogenesis, suggesting that the TSP1 domain is involved in ADAMTS13 angiogenic
      activities. Co-immunoprecipitation experiments provided further evidence that
      ADAMTS13 binds to VEGF via its TSP1 domain.

PMID- 22626949
TI  - An automated computational framework for retinal vascular network labeling and
      branching order analysis.
AB  - Changes in retinal vascular morphology are well known as predictive clinical
      signs of many diseases such as hypertension, diabetes and so on. Computer-aid
      image processing and analysis for retinal vessels in fundus images are effective
      and efficient in clinical diagnosis instead of tedious manual labeling and
      measurement. An automated computational framework for retinal vascular network
      labeling and analysis is presented in this work. The framework includes 1)
      detecting and locating the optic disc; 2) tracking the vessel centerline from
      detected seed points and linking the breaks after tracing; 3) extracting all the
      retinal vascular trees and identifying all the significant points; and 4)
      classifying terminal points into starting points and ending points based on the
      information of optic disc location, and finally assigning branch order for each
      extracted vascular tree in the image. All the modules in the framework are fully
      automated. Based on the results, morphological analysis is then applied to
      achieve geometrical and topological features based on branching order for one
      individual vascular tree or for the vascular network through the retinal vascular
      network in the images. Validation and experiments on the public DRIVE database
      have demonstrated that the proposed framework is a novel approach to analyze and
      study the vascular network pattern, and may offer new insights to the diagnosis
      of retinopathy.

PMID- 22626950
TI  - Assessment of fetal cardiac function using tissue Doppler techniques.
AB  - OBJECTIVE: Tissue Doppler echocardiography is being increasingly used in fetal
      medicine as a clinical and research tool. The objective of this study was to
      review the current status of tissue Doppler imaging (TDI) techniques applied to
      the fetus. METHODS: Fetal cardiac function was evaluated using spectral and color
      TDI modes in normal fetuses and in several clinical conditions. RESULTS: Annular
      peak velocities and their ratios as well as the myocardial performance index were
      evaluated using spectral TDI, and changes throughout gestation were described.
      Color TDI has several limitations in fetal life, particularly the use of low
      frame rates with current methods of acquisition and the lack of normal references
      for deformation parameters. CONCLUSIONS: Despite its limitations, TDI is a
      sensitive and promising method to evaluate fetal cardiac function.

PMID- 22626951
TI  - Intranasal insulin-like growth factor I (IGF-I) as a plausible future treatment
      of depression.
AB  - Depression remains a highly prevalent and mostly recurrent disorder causing an
      increased need to optimize and broaden the current therapy options. An enormous
      body of evidence links the regulation of specific neurotrophic proteins, like the
      brain-derived neurotrophic factor (BDNF), to depression and it may be assumed
      that the behavioral effects of antidepressants require functional BDNF signaling
      in the brain. Another neurotrophin, insulin-like growth factor-I (IGF-I), also
      produces antidepressant-like behavioral effects. Data have shown that BDNF plus
      IGF-I are more effective than either neurotrophin alone in activating
      neurotrophic cascades and promoting survival of hippocampal neurons. In fact, it
      has been suggested that the increase in hippocampal BDNF following antidepressant
      treatment or physical exercise in animal models is IGF-I-dependent and that
      antidepressant treatment increases IGF-I in human cerebrospinal fluid (CSF).
      Thus, BDNF and IGF-I seem to act synergistically in the same cascade of
      transmission and neuroplasticity. In order to avoid the pitfalls of systemic
      application (e.g. possible peripheral side effects) while directly targeting
      central nervous circuitries, the clinical intranasal administration of IGF-I
      appears to be a plausible and promising treatment option of depression.

PMID- 22626952
TI  - The role of erythropoietin in the "stroke belt" phenomenon.
AB  - Global geographic disparities in stroke mortality rates are substantial. In the
      US alone, higher stroke mortality rates are reported in the Southeast part
      particularly along the coastline while lower rates have been observed in the
      Mountain region. The phenomenon has been called the "stroke belt". Although many
      theories have attempted to explain such nonrandom distribution of stroke
      mortality rates, no conclusive explanations have been drawn so far. I hypothesize
      that this nonrandom stroke distribution is related to regional differences in
      individual levels of erythropoietin (EPO), a hormone, which production depends on
      the tissue hypoxia due to variation in altitude. If successful, future studies
      based on this hypothesis may open up new avenues for treatment of such an
      important health issue as stroke. More importantly, future studies based on this
      theory may shed the lights on the mechanism of stroke as well as other diseases
      which have nonrandom geographic distribution not only in the US but also
      internationally.

PMID- 22626953
TI  - Is suicide risk correlated to thyroid weight?
AB  - Disturbances in some endocrine hormones have been implicated in the
      pathophysiology of depression and psychosis. We consider here further the
      hypothesis that there may be a correlation between suicide risk and the weight of
      the thyroid gland. The thyroid weight and other relevant information (sex, BMI)
      were collected retrospectively from 576 autopsies including 299 cases of
      completed suicide, analyzed in the west area of Paris between 1994 and 2010.
      Multiple regression model, adjusted on sex and BMI, confirmed that only for
      subjects more than 60 years of age, deceased by suicide, had a significant
      decrease in their weight of thyroid compared to those who deceased for another
      cause (decrease of around 3g, p=0.03, for age class 60 and over). Our hypothesis
      is that there could exist an anatomical correlate (thyroid weight) among people
      who have committed suicide, especially old individuals. Various hypotheses
      regarding the hypothalamus-pituitary-thyroid axis dysfunction and the
      physiopathology of major depression are proposed and discussed. Further studies
      will be necessary in order to confirm that such a tendency exists on other
      populations.

PMID- 22626954
TI  - Is BDNF biological link between depression and type 2 diabetes mellitus?
AB  - Epidemiological and clinical studies have demonstrated a strong association
      between depression and diabetes. Of note, depression is a risk factor for the
      development of type 2 diabetes mellitus (T2DM), while most patients with T2DM
      also have depression. Despite the abundance of evidence showing an
      epidemiological link between depression and T2DM, the cause of this association
      is still unknown. Brain-derived neurotrophic factor (BDNF) is widely expressed in
      the brain. Biological and clinical studies have repeatedly shown that BDNF is
      important in the pathogenesis of depression and T2DM. Therefore, we propose that
      BDNF may play an important role linking depression and T2DM. Studies examining
      the components of the BDNF system in patients with T2DM and depression may
      provide new understanding into the link between depression and T2DM. Such studies
      might also help us to identify potential treatment targets for these two common
      disorders.

PMID- 22626955
TI  - Aleurites moluccana and its main active ingredient, the flavonoid 2"-O
      rhamnosylswertisin, have promising antinociceptive effects in experimental models
      of hypersensitivity in mice.
AB  - This study investigated the antinociceptive effect of Aleurites moluccana dried
      extract (DE; 125 to 500 mg/kg, p.o.) and the isolated flavonoid 2"-O
      rhamnosylswertisin (5 to 50.6 MUmol/kg, p.o.) using different models of long
      lasting inflammatory and neuropathic pain in mice. Attempts were made to analyse
      the mechanisms through which A. moluccana exerted its effects. A. moluccana DE
      inhibited complete Freund's adjuvant (CFA)-induced mechanical nociception. It was
      also evidenced by a reduction of sensitization in the contralateral hindpaw. The
      extract reversed the mechanical hypersensitivity of partial ligation of sciatic
      nerve (PLSN)-treated animals, similar to gabapentin. In PLSN model, the opioid,
      dopaminergic and oxidonitrergic pathways were involved in the A. moluccana DE
      antinociceptive effects. A single dose of 2"-O-rhamnosylswertisin inhibited the
      carrageenan- and CFA-induced mechanical nociception. Furthermore, the compound
      caused expressive antinociception in PLSN-mice, with inhibition value greater
      than obtained with gabapentin. Oral treatment with the extract or the isolated
      compound attenuated the neutrophil migration and IL-1beta levels following
      carrageenan injection. Of note, A. moluccana DE did not interfere with thermal
      sensitivity in healthy mice. The absence of side effects, including interference
      in locomotor activity, motor performance in animals treated with the extract,
      showed excellent potential for the therapeutic use of this medicinal plant in
      treating persistent pain in humans.

PMID- 22626956
TI  - An auditory brain-computer interface evoked by natural speech.
AB  - Brain-computer interfaces (BCIs) are mainly intended for people unable to perform
      any muscular movement, such as patients in a complete locked-in state. The
      majority of BCIs interact visually with the user, either in the form of
      stimulation or biofeedback. However, visual BCIs challenge their ultimate use
      because they require the subjects to gaze, explore and shift eye-gaze using their
      muscles, thus excluding patients in a complete locked-in state or under the
      condition of the unresponsive wakefulness syndrome. In this study, we present a
      novel fully auditory EEG-BCI based on a dichotic listening paradigm using human
      voice for stimulation. This interface has been evaluated with healthy volunteers,
      achieving an average information transmission rate of 1.5 bits min-1 in full
      length trials and 2.7 bits min-1 using the optimal length of trials, recorded
      with only one channel and without formal training. This novel technique opens the
      door to a more natural communication with users unable to use visual BCIs, with
      promising results in terms of performance, usability, training and cognitive
      effort.

PMID- 22626957
TI  - The demise of Bazett's formula?

PMID- 22626958
TI  - Cardioprotective effect of renalase in 5/6 nephrectomized rats.
AB  - Cardiovascular disease (CVD) remains one of the most common causes of morbidity
      and mortality in patients with chronic renal disease. It has been recently
      postulated that the loss or reduced levels of renalase in patients with chronic
      renal disease are, at least in part, responsible for elevated plasma
      catecholamine levels, which leads to increased CVD. Therefore, the aim of the
      present study was to evaluate whether renalase administration might serve as a
      therapeutic drug, decreasing the severity of CVD in 5/6 nephrectomized (Nx) rats.
      The current study was conducted on 30 male Wistar albino rats divided into the
      following groups: group I: sham-operated rats that received phosphate-buffered
      saline (PBS) subcutaneously (s.c.) for 4 weeks following sham operation, group
      II: rats in which 5/6 Nx was done and then the rats received PBS daily s.c. for 4
      weeks following 5/6 Nx, and group III: rats in which 5/6 Nx was done and then the
      rats received recombinant renalase daily s.c. for 4 weeks following 5/6 Nx. 5/6
      nephrectomy resulted in a significant increase in mean arterial pressure, left
      ventricular (LV)/body weight ratio, LV hydroxyproline concentration, plasma
      creatinine, blood urea nitrogen (BUN), and noradrenaline (NA) levels as well as
      significant decrease in LV papillary muscle developed tension in group II
      compared with the sham-operated group I. Administration of renalase to group III
      resulted in significant amelioration of all studied parameters with the exception
      of plasma creatinine and BUN which were not significantly different from
      nontreated group II. The results of the current study identify renalase as a new
      therapeutic modality that might modulate cardiac function and systemic blood
      pressure in renalase-deficient states like chronic renal disease.

PMID- 22626959
TI  - Donor-specific antibodies after ceasing immunosuppressive therapy, with or
      without an allograft nephrectomy.
AB  - BACKGROUND AND OBJECTIVES: Within the last few years, anti-human leukocyte
      antigen detection assays have significantly improved. This study asked, using the
      Luminex single-antigen assay, whether an allograft nephrectomy allowed donor
      specific alloantibodies to appear that were not previously detected in the serum
      when the failed kidney was still in place. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: After losing the kidney allograft and stopping immunosuppressive
      therapy, the proportions of donor-specific alloantibodies and nondonor-specific
      alloantibodies were compared in patients who had (n=48; group I) and had not
      (n=21; group II) undergone an allograft nephrectomy. Allograft nephrectomies were
      performed at 150 days after kidney allograft loss, and the time between allograft
      nephrectomy and last follow-up was 538 +/- 347 days. RESULTS: At kidney allograft
      loss, donor-specific alloantibodies were detected in three group II patients
      (14.2%) and six group I patients (12.5%). At last follow-up, donor-specific
      alloantibodies were detected in 11 patients (52.4%) without and 39 patients (81%)
      with an allograft nephrectomy (P=0.02). Anti-human leukocyte antigen class I
      donor-specific alloantibodies were positive in 23.8% of group II and 77% of group
      I patients (P<0.001); anti-human leukocyte antigen class II donor-specific
      alloantibodies were positive in 42.8% of group II and 62.5% of group I patients.
      Independent predictive factors for developing donor-specific alloantibodies after
      losing kidney allograft and stopping immunosuppressants were number of anti-human
      leukocyte antigen A/B mismatches at transplantation (zero versus one or more) and
      allograft nephrectomy. CONCLUSIONS: The development of donor-specific
      alloantibodies was significantly greater in patients with a failed kidney who had
      undergone an allograft nephrectomy compared with those patients who had not
      undergone allograft nephrectomy.

PMID- 22626960
TI  - Serum potassium and cause-specific mortality in a large peritoneal dialysis
      cohort.
AB  - BACKGROUND AND OBJECTIVES: Unlike hemodialysis (HD), peritoneal dialysis (PD) is
      a continuous therapy and does not induce myocardial stunning. Yet, the death risk
      in HD and PD patients is similar. This study tested the hypothesis that serum
      potassium abnormalities contribute more to the death risk in PD patients than in
      HD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from patients
      treated in DaVita facilities between July 1, 2001 and June 30, 2006 (n=10,468 PD
      patients; n=111,651 HD patients) were used to determine association of serum
      potassium with mortality. RESULTS: PD patients were significantly more likely to
      have serum potassium < 4 mEq/L, with an adjusted odds ratio of 3.30 (95%
      confidence interval [95% CI], 3.05, 3.56). There was a U-shaped relationship
      between time-averaged serum potassium and all-cause and cardiovascular mortality
      of PD patients, with adjusted hazards ratios of 1.51 for all-cause mortality for
      potassium < 3.5 mEq/L (95% CI, 1.29, 1.76) and 1.52 for potassium >= 5.5 mEq/L
      (95% CI, 1.32, 1.75). The population-attributable risks for all-cause mortality
      for serum potassium < 4.0 and >= 5.5 mEq/L were 3.6% and 1.9%, respectively, in
      PD patients, and 0.8% and 1.5%, respectively, in HD patients. CONCLUSIONS:
      Abnormalities in serum potassium contribute disproportionately to the high death
      risk in PD patients. This may, in part, account for the equivalent cardiac risk
      seen with the two therapies.

PMID- 22626961
TI  - Comparing mandated health care reforms: the Affordable Care Act, accountable care
      organizations, and the Medicare ESRD program.
AB  - In addition to extending health insurance coverage, the Affordable Care Act of
      2010 aims to improve quality of care and contain costs. To this end, the act
      allowed introduction of bundled payments for a range of services, proposed the
      creation of accountable care organizations (ACOs), and established the Centers
      for Medicare and Medicaid Innovation to test new care delivery and payment
      models. The ACO program began April 1, 2012, along with demonstration projects
      for bundled payments for episodes of care in Medicaid. Yet even before many
      components of the Affordable Care Act are fully in place, the Medicare ESRD
      Program has instituted legislatively mandated changes for dialysis services that
      resemble many of these care delivery reform proposals. The ESRD program now
      operates under a fully bundled, case-mix adjusted prospective payment system and
      has implemented Medicare's first-ever mandatory pay-for-performance program: the
      ESRD Quality Incentive Program. As ACOs are developed, they may benefit from the
      nephrology community's experience with these relatively novel models of health
      care payment and delivery reform. Nephrologists are in a position to assure that
      the ACO development will benefit from the ESRD experience. This article reviews
      the new ESRD payment system and the Quality Incentive Program, comparing and
      contrasting them with ACOs. Better understanding of similarities and differences
      between the ESRD program and the ACO program will allow the nephrology community
      to have a more influential voice in shaping the future of health care delivery in
      the United States.

PMID- 22626962
TI  - Incidence and outcomes of BK virus allograft nephropathy among ABO- and HLA
      incompatible kidney transplant recipients.
AB  - BACKGROUND AND OBJECTIVES: ABO-incompatible kidney transplant recipients may have
      a higher incidence of BK virus allograft nephropathy (BKVAN) compared with ABO
      compatible recipients. It is unclear whether HLA-incompatible recipients share
      this risk or whether this phenomenon is unique to ABO-incompatible recipients.  
      DESIGN, SETTING, PARTICIPATION,  MEASUREMENTS:  This study analyzed adult
      incompatible kidney transplant recipients from 1998 to 2010 (62 ABO-incompatible
      and 221 HLA-incompatible) and identified patients in whom BKVAN was diagnosed by
      biopsy (per protocol or for cause). This was a retrospective analysis of a
      prospectively maintained database that compared BKVAN incidence and outcomes
      between ABO- and HLA-incompatible recipients, respectively. BKVAN link to
      rejection and graft accommodation phenotype were also explored. The Johns Hopkins
      Institutional Review Board approved this study. RESULTS: Risk for BKVAN was
      greater among ABO-incompatible than HLA-incompatible patients (17.7% versus 5.9%;
      P=0.008). Of BKVAN cases, 42% were subclinical, diagnosed by protocol biopsy. ABO
      incompatibility and age were independent predictors for BKVAN on logistic
      regression. C4d deposition without histologic features of glomerulitis and
      capillaritis (graft accommodation-like phenotype) on 1-year biopsies of ABO
      incompatible patients with and without BKVAN was 40% and 75.8%, respectively
      (P=0.04). Death-censored graft survival (91%) and serum creatinine level among
      surviving kidneys (1.8 mg/dl) were identical in ABO- and HLA-incompatible
      patients with BKVAN (median, 1399 and 1017 days after transplantation,
      respectively). CONCLUSIONS: ABO-incompatible kidney recipients are at greater
      risk for BKVAN than HLA-incompatible kidney recipients. ABO-incompatible
      recipients not showing the typical graft accommodation-like phenotype may be at
      heightened risk for BKVAN, but this observation requires replication among other
      groups.

PMID- 22626963
TI  - Decoy receptor 3, a novel inflammatory marker, and mortality in hemodialysis
      patients.
AB  - BACKGROUND AND OBJECTIVES: Inflammation is closely associated with cardiovascular
      disease, the leading cause of mortality in patients with CKD. Serum decoy
      receptor 3 (DcR3) is a member of the TNF receptor superfamily. CKD patients have
      higher levels of DcR3 than the general population, but whether DcR3 predicts
      mortality in CKD patients on hemodialysis has not been explored. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: DcR3 levels were measured in 316 prevalent
      hemodialysis patients who were followed up from November 1, 2004, to June 30,
      2009, for cardiovascular and all-cause mortality. RESULTS: The baseline DcR3
      concentration showed a strong positive correlation with inflammatory markers
      including high-sensitivity C-reactive protein, IL-6, intercellular adhesion
      molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). During a
      follow-up period of 54 months, 90 patients died (34 cardiovascular deaths).
      Kaplan-Meier survival analysis showed higher cardiovascular and all-cause
      mortality in patients with higher DcR3 levels. The hazard ratios (95% confidence
      intervals) of the highest versus lowest tertiles of DcR3 were 2.8 (1.1-7.3; P for
      trend=0.04) for cardiovascular mortality and 2.1 (1.1-3.7; P for trend=0.02) for
      all-cause mortality, respectively. Based on the minimal increase in the area
      under the receiver operating characteristic curve from 0.79 to 0.80, the addition
      of DcR3 to established risk factors including VCAM-1, albumin, and IL-6 does not
      improve the prediction of mortality. CONCLUSIONS: Higher DcR3 levels strongly
      correlate with inflammation and independently predict cardiovascular and all
      cause mortality in CKD patients on hemodialysis.

PMID- 22626964
TI  - Tacrolimus-induced rosacea-like dermatitis: a clinical analysis of 16 cases
      associated with tacrolimus ointment application.
AB  - BACKGROUND: Recently, reports have indicated that the continuous use of topical
      calcineurin inhibitors such as tacrolimus may induce rosacea-like dermatitis
      (RD). OBJECTIVE AND METHODS: To assess clinical features of RD associated with
      tacrolimus, 44 cases of patients diagnosed with RD between 2005 and 2010 at our
      hospital were retrospectively reviewed. RESULTS: In total, 22 cases were caused
      by topical steroid use, 8 by topical tacrolimus use, and 8 by consecutive
      treatment with topical steroids and tacrolimus. Clinical presentation was
      basically similar among the 3 groups, although the nose was less frequently
      affected and pustules were rarely observed in the latter 2 sets of cases. Demodex
      mites were often found in smears of skin lesions from patients with RD caused by
      steroids and tacrolimus. Treatment with topical metronidazole was effective in
      most RD patients. CONCLUSION: Topical tacrolimus is becoming an important cause
      of RD along with topical steroids.

PMID- 22626965
TI  - Comparison of microbial communities in marinated and unmarinated broiler meat by
      metagenomics.
AB  - Most raw poultry sold in Finland at the retail level is mixed with marinades
      containing oil, sugar, spices and acetic acid and packaged under modified
      atmosphere. Premature spoilage of marinated poultry preparations has been
      observed and associated with high levels of Leuconostoc spp. in meat. In this
      study we investigated whether marination of broiler fillet strips increased the
      proportion of Leuconostoc spp. in the microbial communities. To obtain a
      comprehensive view of the microbiota, we sequenced total DNA and 16S rRNA gene
      amplicons from the microbial communities. The lactic acid bacterial communities
      were characterized also by identification of colonies. The results showed that
      marinade increased the proportions of the spoilage-associated Leuconostoc
      gasicomitatum in the communities as well as the proportions of Leuconostoc
      gelidum and Lactobacillus spp. The proportions of Carnobacterium, Vagococcus,
      Brochothrix thrermosphacta, Clostridium, Enterobacteriaceae and Vibrio were
      diminished in marinated meat. Analysis of 16S rRNA gene amplicons resulted in 312
      and 284 operational taxonomical units (dissimilarity 0.03) in unmarinated and
      marinated meat, respectively, indicating that the meat communities were more
      diverse than hitherto shown. Metagenomic analysis revealed a number of bacterial
      taxa that have not been associated with late shelf-life meat before, including
      Vagococcus and Vibrio that belonged to the predominating part of the microbial
      community in unmarinated meat. According to the functional analysis of the
      metagenomes, the communities in both marinated and unmarinated poultry were
      characterized by high proportions (15.6% or 17.9%) of genes involved in
      carbohydrate metabolism.

PMID- 22626966
TI  - Secondary metabolites from the root of Ehretia longiflora and their biological
      activities.
AB  - Bioassay-guided fractionation of the methanolic extract of the root of Ehretia
      longiflora (Boraginaceae) afforded eight compounds, ehretiquinone (1),
      ehretiolide (2), ehreticoumarin (3), ehretilactone A (4), ehretilactone B (5),
      ehretiamide (6), ehretine (7), and ehretiate (8), together with 12 known
      compounds (9-20). The relative configuration of 1 was determined by single
      crystal X-ray diffraction. Among the isolates, 1 and prenylhydroquinone (14)
      showed antitubercular activity against Mycobacterium tuberculosis strain H37Rv
      with MIC values of 25.0 and 26.2 MUg/mL, respectively. Moreover, 1 exhibited
      inhibitory effects on N-formylmethionylleucylphenylalanine (fMLP)-induced
      superoxide production, with IC50 value of 0.36+/-0.03MUM.

PMID- 22626967
TI  - Accuracy in contouring of small and low contrast lesions: comparison between
      diagnostic quality computed tomography scanner and computed tomography simulation
      scanner-A phantom study.
AB  - To evaluate the accuracy in detection of small and low-contrast regions using a
      high-definition diagnostic computed tomography (CT) scanner compared with a
      radiotherapy CT simulation scanner. A custom-made phantom with cylindrical holes
      of diameters ranging from 2-9 mm was filled with 9 different concentrations of
      contrast solution. The phantom was scanned using a 16-slice multidetector CT
      simulation scanner (LightSpeed RT16, General Electric Healthcare, Milwaukee, WI)
      and a 64-slice high-definition diagnostic CT scanner (Discovery CT750 HD, General
      Electric Healthcare). The low-contrast regions of interest (ROIs) were delineated
      automatically upon their full width at half maximum of the CT number profile in
      Hounsfield units on a treatment planning workstation. Two conformal indexes,
      CI(in), and CI(out), were calculated to represent the percentage errors of
      underestimation and overestimation in the automated contours compared with their
      actual sizes. Summarizing the conformal indexes of different sizes and contrast
      concentration, the means of CI(in) and CI(out) for the CT simulation scanner were
      33.7% and 60.9%, respectively, and 10.5% and 41.5% were found for the diagnostic
      CT scanner. The mean differences between the 2 scanners' CI(in) and CI(out) were
      shown to be significant with p < 0.001. A descending trend of the index values
      was observed as the ROI size increases for both scanners, which indicates an
      improved accuracy when the ROI size increases, whereas no observable trend was
      found in the contouring accuracy with respect to the contrast levels in this
      study. Images acquired by the diagnostic CT scanner allow higher accuracy on size
      estimation compared with the CT simulation scanner in this study. We recommend
      using a diagnostic CT scanner to scan patients with small lesions (<1 cm in
      diameter) for radiotherapy treatment planning, especially for those pending for
      stereotactic radiosurgery in which accurate delineation of small-sized, low
      contrast regions is important for dose calculation.

PMID- 22626968
TI  - A patient-specific quality assurance study on absolute dose verification using
      ionization chambers of different volumes in RapidArc treatments.
AB  - The recalculation of 1 fraction from a patient treatment plan on a phantom and
      subsequent measurements have become the norms for measurement-based verification,
      which combines the quality assurance recommendations that deal with the treatment
      planning system and the beam delivery system. This type of evaluation has
      prompted attention to measurement equipment and techniques. Ionization chambers
      are considered the gold standard because of their precision, availability, and
      relative ease of use. This study evaluates and compares 5 different ionization
      chambers: phantom combinations for verification in routine patient-specific
      quality assurance of RapidArc treatments. Fifteen different RapidArc plans
      conforming to the clinical standards were selected for the study. Verification
      plans were then created for each treatment plan with different chamber-phantom
      combinations scanned by computed tomography. This includes Medtec intensity
      modulated radiation therapy (IMRT) phantom with micro-ionization chamber (0.007
      cm(3)) and pinpoint chamber (0.015 cm(3)), PTW-Octavius phantom with semiflex
      chamber (0.125 cm(3)) and 2D array (0.125 cm(3)), and indigenously made Circular
      wax phantom with 0.6 cm(3) chamber. The measured isocenter absolute dose was
      compared with the treatment planning system (TPS) plan. The micro-ionization
      chamber shows more deviations when compared with semiflex and 0.6 cm(3) with a
      maximum variation of -4.76%, -1.49%, and 2.23% for micro-ionization, semiflex,
      and farmer chambers, respectively. The positive variations indicate that the
      chamber with larger volume overestimates. Farmer chamber shows higher deviation
      when compared with 0.125 cm(3). In general the deviation was found to be <1% with
      the semiflex and farmer chambers. A maximum variation of 2% was observed for the
      0.007 cm(3) ionization chamber, except in a few cases. Pinpoint chamber
      underestimates the calculated isocenter dose by a maximum of 4.8%. Absolute dose
      measurements using the semiflex ionization chamber with intermediate volume
      (0.125 cm(3)) shows good agreement with the TPS calculated among the detectors
      used in this study. Positioning is very important when using smaller volume
      chambers because they are more sensitive to geometrical errors within the
      treatment fields. It is also suggested to average the dose over the sensitive
      volume for larger-volume chambers. The ionization chamber-phantom combinations
      used in this study can be used interchangeably for routine RapidArc patient
      specific quality assurance with a satisfactory accuracy for clinical practice.

PMID- 22626969
TI  - [Left ventricular aneurysm and differential diagnosis with pseudoaneurysm].
AB  - Left ventricular aneurysm and pseudoaneurysm are two complications of myocardial
      infarction in which the role of imaging is paramount. The authors describe a case
      of a true aneurysm of the posterior wall, for which cardiac magnetic resonance
      was useful, although only intra-operative assessment confirmed the diagnosis.

PMID- 22626970
TI  - MKLs: co-factors of serum response factor (SRF) in neuronal responses.
AB  - Serum response factor (SRF) is a major transcription factor that regulates
      activity-driven gene expression in neurons. Activation of SRF-driven
      transcription occurs through its interaction with two families of co-factors:
      ternary complex factor (TCF) and myocardin-related transcription factors (MRTFs).
      This review focuses on the MRTF family members MKL1 (MAL/MRTF-A/BSAC) and MKL2
      (MRTF-B/MAL16). MKLs share several high-homology domains but a low level of
      sequence identity in the transactivation domain. Both co-activators are expressed
      in the brain and regulate SRF-dependent gene expression. MKL1 and MKL2 function
      as major co-activators of SRF function in the developing mouse brain. MKLs
      inactivation causes ineffective neuronal migration and aberrant neurite outgrowth
      during development. Moreover, inhibition of MKL1 or MKL2 by short-hairpin RNAs
      results in a decreased number of dendritic processes and dendritic length.
      Altogether, MKLs appear to regulate plasticity-related structural changes in
      neurons.

PMID- 22626971
TI  - ESR1 gene status correlates with estrogen receptor protein levels measured by
      ligand binding assay and immunohistochemistry.
AB  - The Estrogen Receptor (ER) is an established predictive marker for the selection
      of adjuvant endocrine treatment in early breast cancer. During the 1990s
      Immunohistochemistry (IHC) replaced cytosol based assays for determination of ER
      status. This study examined the association between ER protein level determined
      by two different methods and ESR1 gene copy number. From 289 primary high-risk
      breast cancer patients, randomized in the Danish Breast Cancer Cooperative Group
      (DBCG) 77C trial, results from cytosolic ER levels were available from ligand
      binding assays. Archival tumor tissue was retrieved from 257 patients. ESR1/CEN-6
      ratio was analyzed successfully by Fluorescence In Situ Hybridization (FISH) in
      220 (86%) patients. ESR1 amplification (ESR1/CEN-6 >= 2.00) was observed in 23%
      of the patients and ESR1 deletion (ESR1/CEN-6 < 0.80) was observed in 32%.
      Further, we identified ESR1 gain (ratio ESR1/CEN-6 from 1.30 to 1.99) in 19% of
      the patients. A positive correlation of ESR1 FISH with both ER-cytosol and ER IHC
      was found (p < 0.0001). Amplification and gain of the ESR1 gene are associated
      with higher ER protein content measured by ligand binding assay and a more
      intense nuclear staining by IHC compared to tumors with normal ESR1 gene status.
      Major variations in ER measured by ligand binding assay and IHC are observed
      within all ESR1 copy number subgroups and other mechanisms than gene copy number
      seem to contribute to the ER protein content in the tumors.

PMID- 22626973
TI  - Age-related learning deficits can be reversible in honeybees Apis mellifera.
AB  - Many animals are characterized by declining brain function at advanced ages,
      including honeybees (Apis mellifera). Variation in honeybee social development,
      moreover, results in individual differences in the progression of aging that may
      be accelerated, delayed, and sometimes reversed by changes in behavior. Here, we
      combine manipulations of social development with a measurement of sensory
      sensitivity, Pavlovian (associative) learning, and a proteomic technique to study
      the brain of aged honeybees. First, we confirm that sensory sensitivity can
      remain intact during aging, and that age-associated learning deficits are
      specific to bees that forage, a behavior typically expressed after a period of
      nursing activity. These initial data go beyond previous findings by showing how
      foragers age in social groups of different age compositions and sizes.
      Thereafter, we establish that learning ability can recover in aged foragers that
      revert to nursing tasks. Finally, we use liquid chromatography coupled to tandem
      mass spectrometry (LC-MS(2)) to describe proteomic differences between central
      brains, from reverted former foragers that varied in recovery of learning
      performance, and from nurse bees that varied in learning ability but never
      foraged. We find that recovery is positively associated with levels of stress
      response/cellular maintenance proteins in the central brain, while variation in
      learning before aging is negatively associated with the amounts of metabolic
      enzymes in the brain tissue. Our work provides the strongest evidence, thus far,
      for reversibility of learning deficits in aged honeybees, and indicates that
      recovery-related brain plasticity is connected to cellular stress resilience,
      maintenance and repair processes.

PMID- 22626972
TI  - The specific contributions of force and velocity to muscle power in older adults.
AB  - The purpose of this study is to examine the relative importance of the force
      based and velocity-based measures of muscle performance to explain inter
      individual differences in power production capability and functional task
      performance. Participants included seventy-nine men and women: middle-aged
      healthy adults (MH: 40-55years), older healthy adults (OH: 70-85years), and older
      adults with mobility limitations (OML: 70-85years). Muscle power at 180 degrees
      /s, isometric maximal torque, and maximal contraction velocity at 40% 1RM were
      measured during unilateral leg extension. The Short Physical Performance Battery
      (SPPB) was used to differentiate between healthy and mobility limited older
      adults. Functional task performance was assessed using multiple chair rise and
      stair climb tests. Leg extensor force (torque), but not maximal contraction
      velocity, was significantly associated with muscle power in MH. Both torque and
      velocity were significantly associated with muscle power in OH. Maximal velocity,
      but not torque, was associated with power in OML. Maximal velocity demonstrated
      an association with multiple chair rise time and stair climb time in OML, but not
      MH or OH. It is concluded that movement velocity is an increasingly important
      determinant of maximal power output with advancing age. Furthermore, movement
      velocity is also a critical component of functional task performance with aging
      and may contribute to functional deficits. These findings help to explain why the
      rate-dependent variable power has emerged as a critical component of both
      assessment and rehabilitation of muscular performance and physical function in
      older adults.

PMID- 22626974
TI  - Tissue distribution and cancer growth inhibition of magnetic lipoplex-delivered
      type 1 insulin-like growth factor receptor shRNA in nude mice.
AB  - The targeted delivery of therapeutic genes into specific tissues, as well as the
      determination of the biological fate and potential toxicity of nanoparticles,
      remains a highly relevant challenge for gene-based therapies. Type 1 insulin-like
      growth factor receptor (IGF-1R), an important oncogene, is frequently over
      expressed in lung cancer and mediates cancer cell proliferation as well as tumor
      growth. In our previous studies, we have successfully applied gene delivery
      mediated by commercially available nanoparticles (CombiMAG) under a magnetic
      field, which suppresses IGF-1R expression in a non-small cell lung cancer cell
      line (A549) in vitro. In the present study, we aimed to investigate the
      biological distribution and target tumor suppression of magnetofection, as well
      as its potential toxicity via CombiMAG-carrying plasmids expressing green
      fluorescent protein (GFP) and short hairpin RNAs (shRNAs) targeting IGF-1R
      (pGFPshIGF-1Rs) in tumor-bearing mice. The peak expression in various organs
      appeared 48 h after transfection. Transgene expression via magnetofection was 3
      fold improvement than via lipofection. On the 30th day after injection, the tumor
      size and weight of the CombiMAG-treated group (789.32 +/- 39.43 mm(3), 105.5 +/-
      6.1 mg) were significantly decreased compared with those of the lipofection group
      (893.83 +/- 31.23 mm(3), 164.5 +/- 9.1 mg; P< 0.05), and the suppression rate was
      ~36%. After a 30-day observation, the injection of CombiMAG did not cause any
      apparent toxicity. Therefore, IGF-1R shRNA nanoparticles can be valuable and safe
      delivery agents for RNA interference therapy to tumors in vivo.

PMID- 22626975
TI  - Ellagic acid facilitates indomethacin-induced gastric ulcer healing via COX-2 up
      regulation.
AB  - The mechanism of indomethacin-induced gastric ulcer healing by ellagic acid (EA)
      in experimental mice model is described in our study. Ulcer index (UI) and
      myeloperoxidase (MPO) activity of the stomach tissues showed maximum ulceration
      on the third day after indomethacin (18 mg/kg, single dose) administration.
      Preliminary observation of UI and MPO activity suggests that EA possesses ulcer
      healing activity. Other anti-ulcer parameters such as the levels of prostaglandin
      E(2), cyclooxygenase (COX) 1 and 2 enzymes, anti-inflammatory cytokines
      [interleukin (IL)-4 and -5], pro-angiogenic factors, e.g. vascular endothelial
      growth factor, hepatocyte growth factor (HGF), and endothelial growth factor
      (EGF) were down-regulated by indomethacin. EA (7 mg/kg/day) treatment for 3 days
      shifted the indomethacin-induced pro-inflammatory biochemical parameters to the
      healing side. These activities were correlated with the ability of EA to alter
      the COX-2-dependent healing pathways. The ulcer-healing activity of EA was,
      however, compromised by pre-administration of the specific COX-2 inhibitor,
      celecoxib, and NS-398. Taken together, these results suggested that the EA
      treatment accelerates ulcer healing by inducing IL-4, EGF/HGF levels and enhances
      COX-2 expression.

PMID- 22626976
TI  - Angiotensin II generation in vivo: does it involve enzymes other than renin and
      angiotensin-converting enzyme?

PMID- 22626977
TI  - Mathematical models to describe iontophoretic transport in vitro and in vivo and
      the effect of current application on the skin barrier.
AB  - The architecture and composition of the stratum corneum make it a particularly
      effective barrier against the topical and transdermal delivery of hydrophilic
      molecules and ions. As a result, different strategies have been explored in order
      to expand the range of therapeutic agents that can be administered by this route.
      Iontophoresis involves the application of a small electric potential to increase
      transport into and across the skin. Since current flow is preferentially via
      transport pathways with at least some aqueous character, it is ideal for
      hydrosoluble molecules containing ionisable groups. Hence, the physicochemical
      properties that limit partitioning and passive diffusion through the
      intercellular lipid matrix are beneficial for electrically-assisted delivery. The
      presence of fixed ionisable groups in the skin (pI 4-4.5) means that application
      of the electric field results in a convective solvent flow (i.e., electroosmosis)
      in the direction of ion motion so as to neutralise membrane charge. Hence, under
      physiological conditions, cation electrotransport is due to both electromigration
      and electroosmosis-their relative contribution depends on the formulation
      conditions and the physicochemical properties of the permeant. Different
      mathematical models have been developed to provide a theoretical framework in
      order to explain iontophoretic transport kinetics. They usually involve solutions
      of the Nernst-Planck equation - using either the constant field (Goldman) or
      electroneutrality (Nernst) approximations - with or without terms for the
      convective solvent flow component. Investigations have also attempted to
      elucidate the nature of ion transport pathways and to explain the effect of
      current application on the electrical properties of the skin-more specifically,
      the stratum corneum. These studies have led to the development of different
      equivalent circuit models. These range from simple parallel arrangements of a
      resistor and a capacitor to the inclusion of the more esoteric "constant phase
      element"; the latter provides a better mathematical description of the "non
      ideal" behaviour of skin impedance. However, in addition to simply providing a
      "mathematical" fit of the observed data, it is essential to relate these circuit
      elements to biological structures present in the skin. More recently, attention
      has also turned to what happens when the permeant crosses the epidermis and
      reaches the systemic circulation and pharmacokinetic models have been proposed to
      interpret data from iontophoretic delivery studies in vivo. Here, we provide an
      overview of mathematical models that have been proposed to describe (i) the
      effect of current application on the skin and the implications for potential
      iontophoretic transport pathways, (ii) electrotransport kinetics and (iii) the
      fate of iontophoretically delivered drugs once they enter the systemic
      circulation.

PMID- 22626979
TI  - Improved input parameters for diffusion models of skin absorption.
AB  - To use a diffusion model for predicting skin absorption requires accurate
      estimates of input parameters on model geometry, affinity and transport
      characteristics. This review summarizes methods to obtain input parameters for
      diffusion models of skin absorption focusing on partition and diffusion
      coefficients. These include experimental methods, extrapolation approaches, and
      correlations that relate partition and diffusion coefficients to tabulated
      physico-chemical solute properties. Exhaustive databases on lipid-water and
      corneocyte protein-water partition coefficients are presented and analyzed to
      provide improved approximations to estimate lipid-water and corneocyte protein
      water partition coefficients. The most commonly used estimates of lipid and
      corneocyte diffusion coefficients are also reviewed. In order to improve modeling
      of skin absorption in the future diffusion models should include the vertical
      stratum corneum heterogeneity, slow equilibration processes, the absorption from
      complex non-aqueous formulations, and an improved representation of dermal
      absorption processes. This will require input parameters for which no suitable
      estimates are yet available.

PMID- 22626980
TI  - Lanthanide-doped upconverting luminescent nanoparticle platforms for optical
      imaging-guided drug delivery and therapy.
AB  - Lanthanide-doped upconverting luminescent nanoparticles (UCNPs) are promising
      materials for optical imaging-guided drug delivery and therapy due to their
      unique optical and chemical properties. UCNPs absorb low energy near-infrared
      (NIR) light and emit high-energy shorter wavelength photons. Their special
      features allow them to overcome various problems associated with conventional
      imaging probes and to provide versatility for creating nanoplatforms with both
      imaging and therapeutic modalities. Here, we discuss several approaches to
      fabricate and utilize UCNPs for traceable drug delivery and therapy.

PMID- 22626981
TI  - Huprine X and huperzine A improve cognition and regulate some neurochemical
      processes related with Alzheimer's disease in triple transgenic mice (3xTg-AD).
AB  - BACKGROUND: Different studies have established that cholinergic neurodegeneration
      could be a major pathological feature of Alzheimer's disease (AD). Thus,
      enhancement of the central cholinergic neurotransmission has been regarded as one
      of the most promising strategies for the symptomatic treatment of AD, mainly by
      means of reversible acetylcholinesterase inhibitors (AChEIs). The cognitive
      enhancing properties of both huprine X, a new AChEI, and the structurally related
      huperzine A, as well as their effects on the regulation of several neurochemical
      processes related to AD have been studied in triple transgenic mice (3xTg-AD).
      METHODS: Seven-month-old homozygous 3xTg-AD male mice, which received chronic
      intraperitoneal treatment with either saline, huprine X (0.12 umol.kg(-1)) or
      huperzine A (0.8 umol.kg(-1)) were subjected to a battery of behavioural tests
      after 3 weeks of treatment and thereafter the brains were dissected to study the
      neurochemical effects induced by the two AChEIs. RESULTS: Treatments with huprine
      X and huperzine A improved learning and memory in the Morris water maze and some
      indicators of emotionality without inducing important adverse effects. Moreover,
      huprine X and huperzine A activate protein kinase C/mitogen-activated protein
      kinase pathway signalling, alpha-secretases (ADAM 10 and TACE) and increase the
      fraction of phospho-glycogen synthase kinase 3-beta. CONCLUSION: Results obtained
      herein using a sample of 3xTg-AD animals strongly suggest that the treatment with
      the two AChEIs not only improves the cognitive performance of the animals but
      also induces some neurochemical changes that could contribute to the beneficial
      effects observed.

PMID- 22626982
TI  - A neglected diagnosis in severe diarrhea, thrombocytopenia, and elevated serum
      creatinine levels.

PMID- 22626983
TI  - SIR: Deterministic protein inference from peptides assigned to MS data.
AB  - Currently the bottom up approach is the most popular for characterizing protein
      samples by mass spectrometry. This is mainly attributed to the fact that the
      bottom up approach has been successfully optimized for high throughput studies.
      However, the bottom up approach is associated with a number of challenges such as
      loss of linkage information between peptides. Previous publications have
      addressed some of these problems which are commonly referred to as protein
      inference. Nevertheless, all previous publications on the subject are
      oversimplified and do not represent the full complexity of the proteins
      identified. To this end we present here SIR (spectra based isoform resolver) that
      uses a novel transparent and systematic approach for organizing and presenting
      identified proteins based on peptide spectra assignments. The algorithm groups
      peptides and proteins into five evidence groups and calculates sixteen parameters
      for each identified protein that are useful for cases where deterministic protein
      inference is the goal. The novel approach has been incorporated into SIR which is
      a user-friendly tool only concerned with protein inference based on imports of
      Mascot search results. SIR has in addition two visualization tools that
      facilitate further exploration of the protein inference problem.

PMID- 22626978
TI  - Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.
AB  - Complications in treatment of large bone defects using bone grafting still
      remain. Our understanding of the endogenous bone regeneration cascade has
      inspired the exploration of a wide variety of growth factors (GFs) in an effort
      to mimic the natural signaling that controls bone healing. Biomaterial-based
      delivery of single exogenous GFs has shown therapeutic efficacy, and this likely
      relates to its ability to recruit and promote replication of cells involved in
      tissue development and the healing process. However, as the natural bone healing
      cascade involves the action of multiple factors, each acting in a specific
      spatiotemporal pattern, strategies aiming to mimic the critical aspects of this
      process will likely benefit from the usage of multiple therapeutic agents. This
      article reviews the current status of approaches to deliver single GFs, as well
      as ongoing efforts to develop sophisticated delivery platforms to deliver
      multiple lineage-directing morphogens (multiple GFs) during bone healing.

PMID- 22626984
TI  - Multi-color CD34+ progenitor-focused flow cytometric assay in evaluation of
      myelodysplastic syndromes in patients with post cancer therapy cytopenia.
AB  - Bone marrow assessment for myelodysplastic syndrome (MDS) in a patient who
      develops cytopenia(s) following cancer therapy is challenging. With recent
      advances in multi-color flow cytometry immunophenotypic analysis, a CD34(+)
      progenitor-focused 7-color assay was developed and tested in this clinical
      setting. This assay was first performed in 73 MDS patients and 53 non-MDS
      patients (developmental set). A number of immunophenotypic changes were
      differentially observed in these two groups. Based on the sensitivity,
      specificity and reproducibility, a core panel of markers was selected for final
      assessment that included increased total CD34(+) myeloblasts; decreased stage I
      hematogones; altered CD45/side scatter; altered expression of CD13, CD33, CD34,
      CD38, CD117, and CD123; aberrant expression of lymphoid or mature myelomonocytic
      antigens on CD34(+) myeloblasts; and several marked alterations in maturing
      myelomonocytic cells. The data were translated into a simplified scoring system
      which was then used in 120 patients with cytopenia(s) secondary to cancer therapy
      over a 2-year period (validation set). With a median follow-up of 11 months, this
      assay demonstrated 89% sensitivity, 94% specificity, and 92% accuracy in
      establishing or excluding a diagnosis of MDS.

PMID- 22626986
TI  - From genes to cognition in tuberous sclerosis: implications for mTOR inhibitor
      based treatment approaches.
AB  - Tuberous sclerosis (TSC) is a neurocutaneous disorder with an autosomal-dominant
      pattern of inheritance and is caused by heterozygous mutations in the TSC1 or
      TSC2 gene. Neuropsychiatric conditions, including intellectual disability, autism
      and epilepsy, are highly prevalent in TSC populations. Here, I review recent
      findings that shed light on some of the neurobiological mechanisms that may
      contribute to the pathogenesis of TSC-associated neuropsychiatric impairments.
      Emerging intervention studies in animal models show striking effects of mTORC1
      inhibitors on TSC-related CNS manifestations. Translational studies that assess
      the effects of mTORC1 inhibitors on neuropsychiatric phenotypes in human TSC
      individuals are underway. This article is part of the Special Issue entitled
      'Neurodevelopmental Disorders'.

PMID- 22626985
TI  - Role of presynaptic metabotropic glutamate receptors in the induction of long
      term synaptic plasticity of vesicular release.
AB  - While postsynaptic ionotropic and metabotropic glutamate receptors have received
      the lions share of attention in studies of long-term activity-dependent synaptic
      plasticity, it is becoming clear that presynaptic metabotropic glutamate
      receptors play critical roles in both short-term and long-term plasticity of
      vesicular transmitter release, and that they act both at the level of voltage
      dependent calcium channels and directly on proteins of the vesicular release
      machinery. Activation of G protein-coupled receptors can transiently inhibit
      vesicular release through the release of Gbetagamma which binds to both voltage
      dependent calcium channels to reduce calcium influx, and directly to the C
      terminus region of the SNARE protein SNAP-25. Our recent work has revealed that
      the binding of Gbetagamma to SNAP-25 is necessary, but not sufficient, to elicit
      long-term depression (LTD) of vesicular glutamate release, and that the
      concomitant release of Galpha(i) and the second messenger nitric oxide are also
      necessary steps in the presynaptic LTD cascade. Here, we review the current state
      of knowledge of the molecular steps mediating short-term and long-term plasticity
      of vesicular release at glutamatergic synapses, and the many gaps that remain to
      be addressed. This article is part of a Special Issue entitled 'Metabotropic
      Glutamate Receptors'.

PMID- 22626987
TI  - Measuring action potential-evoked transmission at individual synaptic contacts.
AB  - In the neuronal culture experimental system, the total synaptic connection
      between two neurons can consist of large numbers of synaptic sites, each behaving
      probabilistically. Studies of synaptic function with paired recordings typically
      consider the summed response across all of these sites and from this infer the
      average response. Understanding of synaptic transmission and plasticity could be
      improved by examination of activity at as few synaptic sites as possible. To this
      end, we develop a system for recording responses from individual contacts. It
      relies on a precisely regulated pneumatic/hydrostatic pressure system to create a
      microenvironment within which individual synapses are active, and an acoustic
      signature method to monitor the stability of this microenvironment noninvasively.
      With this method we are able to record action potential-evoked postsynaptic
      currents consistent with individual quanta. The approach does not distort
      synaptic current waveforms and permits stable recording for several hours. The
      method is applied to address mechanisms of short-term plasticity, the variability
      of latency at individual synaptic sites and, in a preliminary experiment, the
      independence of nearby synapses on the same axon.

PMID- 22626988
TI  - Predicting torsade de pointes in acquired long QT syndrome: optimal
      identification of critical QT interval prolongation.
AB  - OBJECTIVES: To determine the optimal method of ventricular repolarization
      assessment in predicting torsade de pointes (Tdp) in acquired long QT syndrome
      (LQTS) within the context of the recommended cutoff levels of concern for
      QT/corrected QT (QTc) interval prolongation. METHODS: Twenty-nine patients with
      LQTS and Tdp (age 66 +/- 11 years) and matched controls were studied. Standard 12
      lead electrocardiograms were utilized to evaluate ventricular repolarization by
      using six different QT/JT heart rate correction methods. We compared the
      distribution of QT/QTc and JT/corrected JT intervals of patients who experienced
      Tdp with (1) the corresponding intervals in the matched controls and (2) the
      recommended cutoff levels for QT/JT interval prolongation. RESULTS: Patients with
      Tdp (23 with narrow QRS, 6 with wide QRS) had longer ventricular repolarization
      intervals than controls (p < 0.001). For patients with narrow QRS, the QTc
      interval as determined firstly by the method of Hodges (t = 7.56, c = 0.933, p <
      0.001), followed by the Nomogram and Fridericia methods, best discriminated Tdp
      patients from controls and provided the optimal balance between sensitivity and
      specificity at all three cutoff levels. For patients with wide QRS, the JT
      interval or, alternatively, the Hodges method seemed most useful. CONCLUSIONS:
      Assessment of ventricular repolarization by the Hodges, Nomogram and Fridericia
      methods performs best in identifying subsequent Tdp.

PMID- 22626989
TI  - General anaesthesia is associated with adverse cardiac outcome after endovascular
      aneurysm repair.
AB  - OBJECTIVES: Endovascular aneurysm repair (EVAR) is associated with reduced
      cardiac stress compared with open repair and is an attractive therapeutic option,
      especially in cardiac fragile patients. General and locoregional anaesthesia
      differ regarding the stress response evoked by surgery. The aim of the study is
      to compare the incidence of cardiac events after EVAR under general or
      locoregional anaesthesia. METHODS: A total of 302 consecutive patients undergoing
      infrarenal EVAR between 2002 and 2011 were analysed in this retrospective cohort
      study. Selection of anaesthesia type was at the discretion of the treating
      physicians. Medical history, medication use, anaesthesia technique and follow-up
      were obtained. The study end point was 30-day cardiac complications, including
      cardiac death, non-fatal myocardial infarction, heart failure, ventricular
      arrhythmia and troponin T release. Multivariable analysis, adjusted for the
      propensity of receiving a locoregional technique and cardiac risk factors
      according to the Revised Cardiac Risk Index, was used to assess the association
      between cardiac events and anaesthesia type. RESULTS: A total of 173 patients
      underwent general anaesthesia and 129 locoregional anaesthesia. Obesity, aspirin
      use and therapeutic anticoagulation were more common in patients receiving
      general anaesthesia. Cardiac events were observed in 13.3% of patients receiving
      general anaesthesia and in 4.7% of patients receiving locoregional anaesthesia (P
      = 0.02), or 6.4% versus .8% (P = 0.02) when asymptomatic troponin release is
      excluded from the end point. In the general anaesthesia group, two cardiac
      deaths, six non-fatal myocardial infarctions, two cases of non-fatal heart
      failure, one non-fatal cardiac arrest and 12 cases of troponin T release were
      observed, compared with one myocardial infarction and five cases of troponin T
      release in the locoregional anaesthesia group. In multivariable analysis, general
      anaesthesia was associated with adverse cardiac events (odds ratio (OR) 3.8; 95%
      confidence interval (CI) 1.1-12.9). Non-cardiac complications occurred in 11.6%
      of patients in both groups (P = 1.00). CONCLUSION: General anaesthesia was
      associated with an increased risk of cardiac events in EVAR, compared with
      locoregional anaesthesia.

PMID- 22626990
TI  - Discrepancies between treatment standards and clinical reality: the role of
      population-based practice registries - commentary on the first VASCUNET report.

PMID- 22626991
TI  - A comparison of epidural and cerebrospinal fluid glucose in parturients at term:
      an observational study.
AB  - BACKGROUND: Detecting inadvertent dural puncture during labour epidural insertion
      can be difficult when using a loss of resistance to saline technique. Testing
      fluid for glucose that leaks from a Tuohy needle may confirm the presence of
      cerebrospinal fluid and infer inadvertent dural puncture. This study compared the
      glucose content of intrathecal fluid obtained during spinal anaesthesia for
      elective caesarean delivery with that of fluid from a Tuohy needle or epidural
      catheter when establishing epidural analgesia for labour. METHODS: Women aged
      >=18 years undergoing elective caesarean delivery and labouring parturients who
      requested epidural analgesia were recruited prospectively in a tertiary referral
      centre over a three-month period. Fluid was collected into a sterile container
      either during spinal anaesthesia or from a labour epidural needle. Glucose
      content was evaluated using a bedside blood glucometer and laboratory
      colorimetric analyzer. RESULTS: Of the 118 women approached, 115 participated.
      All 40 women having spinal anaesthesia and 2/75 (2.7%) women having epidural
      analgesia, in whom inadvertent dural puncture was subsequently confirmed, had
      fluid samples testing positive for glucose. Median [range] laboratory glucose
      readings were 2.9 [1.3-5.1] mmol/L for cerebrospinal fluid and <0.3 mmol/L in
      fluid that leaked from a Tuohy needle (P=0.0001). CONCLUSION: When using a loss
      of resistance to saline technique for epidural catheter placement, bedside
      glucometer testing of fluid leaking from the epidural needle may be of value in
      the early detection of inadvertent dural puncture.

PMID- 22626992
TI  - Perioperative management of a parturient with antithrombin deficiency and the
      role of thromboelastography.

PMID- 22626993
TI  - Emergency caesarean delivery of a parturient with undiagnosed pemphigoid
      gestationis.

PMID- 22626994
TI  - Prospective evaluation of systolic arterial pressure control with a phenylephrine
      infusion regimen during spinal anaesthesia for caesarean section.
AB  - BACKGROUND: Hypotension and nausea occur frequently during spinal anaesthesia for
      caesarean section. The aim of this evaluation was to assess systolic arterial
      pressure control with our routine prophylactic intravenous phenylephrine infusion
      regimen. We audited a local standard for an incidence of hypotension of <= 25%
      during the first 15 min of anaesthesia. METHODS: One hundred healthy women
      undergoing elective caesarean section were assessed. Following intravenous
      preload with 10 mL/kg Hartmann's solution, 0.5% hyperbaric bupivacaine 2.8 mL
      combined with diamorphine 400 MUg was given intrathecally in the sitting
      position. Intravenous phenylephrine was then started at 67 MUg/min (the maximum
      rate). Systolic arterial pressure was recorded every 2 min. The infusion was
      titrated, according to local guidelines, to maintain systolic arterial pressure
      close to baseline. RESULTS: The median dose of phenylephrine given by infusion
      was 1000 [interquartile range 670-1000]MUg, with 51 patients not requiring any
      change to the infusion rate. Eleven patients (11%, 95% CI 6-19) developed
      hypotension, defined as a systolic arterial pressure <80% of baseline. A further
      four patients were given a bolus of phenylephrine for suspected hypotension. The
      incidence of hypotension or suspected hypotension was therefore 15% (95% CI 9
      24). Thirteen patients (13%, 95% CI 7-21) developed nausea. No patient vomited.
      CONCLUSIONS: Our routine phenylephrine infusion regimen was effective at
      minimizing hypotension and nausea during relatively high-dose spinal anaesthesia.
      This was achieved with a low intervention rate, in conjunction with a 2-min
      rather than a 1-min non-invasive blood pressure cycle time and a relatively low
      volume of intravenous fluid.

PMID- 22626995
TI  - Natural exceptions to normal gonad development in mammals.
AB  - Gonads are the only organs with 2 possible developmental pathways, testis or
      ovary. A consequence of this unique feature is that mutations in genes
      controlling gonad development give rise not only to gonadal malformation or
      dysfunction but also to frequent cases of sex reversal, including XY females, XX
      males and intersexes. Most of our current knowledge on mammalian sex
      determination, the genetic process by which the gonadal primordia are committed
      to differentiate as either testes or ovaries, has derived mainly from the study
      of sex-reversed mice obtained by direct genetic manipulation. However, there are
      also numerous cases of natural exceptions to normal gonad development which have
      been described in a variety of mammals, including both domestic and wild species.
      Here, we review the most relevant cases of: (1) natural, non-induced sex reversal
      and intersexuality described in laboratory rodents, including Sxr and B6-Y(DOM)
      mice; (2) sex reversal in domestic animals, including freemartinism in bovids and
      pigs, XX sex reversal in pigs, goats and dogs, XY sex reversal in the horse, and
      sex chromosome chimerism and sex reversal in the cat, and (3) sex reversal in
      wild mammals, including the generalised true hermaphroditism described in talpid
      moles, XY sex reversal in Akodon, Microtus and Dicrostonyx species, males lacking
      a Y chromosome and SRY in Ellobius lutescens, the X* chromosome of Myopus
      schisticolor, and sex chromosome mosaicism and X0 females in Microtus oregoni.
      These studies are necessary to elucidate particular aspects of mammalian gonad
      development in some instances and to understand how the genetic mechanisms
      controlling gonad development have evolved.

PMID- 22626996
TI  - Expression of CD147, BIGH3 and Stathmin and their potential role as diagnostic
      marker in patients with urothelial carcinoma of the bladder.
AB  - BACKGROUND: Urothelial carcinoma of the bladder is characterised by very high
      recurrence rate, followed up by cystoscopy which being invasive technique makes
      the need for non-invasive markers important for Transitional Cell Carcinoma (TCC)
      detection. CD147 is a transmembrane protein highly expressed in tumour cells
      which aids in tumour invasion and growth. BIGH3, an Extracellular matrix protein
      (ECM) which interacts with various ECM component in different tissue system and
      Stathmin(STMN1) is cytosolic microtubule destabilising protein also called as
      Oncoprotein18 due to its role in tumour promotion. So far the expression of BIGH3
      and STMN1 remains undetermined in cancer subjects including TCC. We therefore
      studied the levels and molecular expression of these molecules in TCC patients,
      to evaluate their usefulness as diagnostic markers. METHODS: Thirty consecutive
      TCC patients and two sets of control- 15 Benign prostatic hyperplasia (BPH)
      patient and 15 healthy were taken. Serum and urine levels of these molecules were
      estimated by ELISA and relative mRNA expression by Q-PCR from tumour and normal
      urothelium. Post-Hoc analysis and ROC curve were determined to evaluate the
      significance and sensitivity and specificity. RESULTS: The mean concentrations of
      these molecules were found to be significantly increased (p<0.001) in the serum
      and urine of TCC patients, with varying significance in each grade for different
      molecules. The urinary levels of CD147 (67 pg/ml) and serum STMN1 concentration
      (1.38 ng/ml) showed a specific increase as compared to the controls, while BIGH3
      was elevated in both serum and urine samples. Molecular (mRNA) expression was
      elevated in the high grade (Muscle Invasive) stage of the disease for all the
      molecules, with a significant 3-fold increase that correlated with disease
      severity being observed for STMN1. ROC analysis gave optimal combination of
      sensitivity and specificity for diagnosis of the disease in urine and serum
      sample for STMN1. CONCLUSION: Of CD147, BIGH3 and STMN1, significant results were
      obtained for STMN1 and it could serve as the best possible diagnostic marker for
      TCC detection in future.

PMID- 22626997
TI  - Effect of glenoid implant design on glenohumeral stability: an experimental
      study.
AB  - BACKGROUND: Though several glenoid implants were developed over the past years, a
      high rate of glenoid loosening remains. This complication is linked to the
      glenohumeral stability, defined as humeral head translation. In an intact
      shoulder, this concept is ensured by all active and passive elements,
      particularly the labrum. Two features of a glenoid implant can be adjusted to
      improve the stability, or, in other words, to decrease the translations: the
      first is the mismatch, defined as the difference of curvature between the
      prosthetic head and glenoid; the second is the shape of the glenoid component.
      Therefore, the objective of this study was to compare the performance of 2
      glenoid components (Ceraver, Roissy, France): (1) a standard design and (2) a
      design named "labrum design" with a superior part simulating the anatomic labrum.
      METHODS: An experimental device was developed to evaluate forces and kinematics.
      The device simulated active, dynamic and continuous abduction of an entire arm.
      It reproduced the Scapulo-Humeral Rhythm. The labrum design was installed first.
      To evaluate the effect of mismatch on the glenohumeral stability, 3 humeral heads
      were tested, corresponding to the ones recommended by the company. The experiment
      was repeated for the standard design. FINDINGS: The results obtained show a
      general decrease of the prosthetic head translation with the labrum design
      compared to the standard design. No noticeable effect of mismatch was found.
      INTERPRETATION: A proof of concept of the interest of the artificial labrum was
      provided since it improved the glenohumeral stability.

PMID- 22626998
TI  - Train to retain or drain? The need for a global survey for sitting allowances.

PMID- 22626999
TI  - Quality of life among healthcare workers: a multicentre cross-sectional study in
      Italy.
AB  - OBJECTIVE: To evaluate the quality of life among doctors, nurses, and
      occupational safety and health technologists (OSHT). STUDY DESIGN: Cross
      sectional study was undertaken in a population of healthcare workers in 10
      Italian regions. METHODS: The Italian version of short form-36 (SF-36) was
      anonymously and voluntarily self-administered by participants to assess the
      perceived health-related quality of life (HRQOL). The HRQOL scores for the sample
      and the Italian population were compared. A multiple linear regression was
      performed to assess the influence of age, gender, role, socializing time, working
      time, years spent in healthcare and years spent in the specific department on the
      SF-36 score. RESULTS: The sample included 324 healthcare workers [57.1% women,
      mean age 39.0 (standard deviation 10.2) years]: 52.6% were medical doctors, 36.8%
      were nurses and 10.5% were OSHTs. Workers with a career of >15 years achieved a
      general health score lower than that of workers with a shorter career, while
      those who spent more time in socializing activities achieved a higher mental
      health score. The multivariate analysis showed that increasing age is positively
      related to role emotional levels (beta = 0.243; P = 0.002), while it appears to
      be inversely related to general health (beta = -0.218; P = 0.007) and physical
      function (beta = -0.246; P = 0.001). Nurses had lower scores for bodily pain
      (beta = -0.214; P < 0.001), social function (beta = -0.242; P = 0.001) and role
      emotional (beta = -0.211; P = 0.006) compared with doctors. Compared with the
      general Italian population, healthcare workers had higher scores for general
      health, physical function, role physical, bodily pain and mental health, and
      lower scores for vitality, social function and role emotional. CONCLUSIONS:
      Healthcare workers have different levels of HRQOL related to their professional
      role. In particular, nurses have lower quality of life. These results may help to
      identify the main roles and attitudes that could cause frustration,
      dissatisfaction and emotional stress in healthcare workers.

PMID- 22627000
TI  - Assessing the optimal time point for the measurement of extrastriatal serotonin
      transporter binding with 123I-FP-CIT SPECT in healthy, male subjects.
AB  - (123)I-N-omega-fluoropropyl-2beta-carboxymethoxy-3beta-(4-iodophenyl)nortropane
      ((123)I-FP-CIT) is commonly used to assess the dopamine transporter in the
      striatum. However, recent studies suggest that this tracer may be used also to
      assess binding to monoamine transporters in the midbrain or diencephalon, which
      may reflect predominantly serotonin transporter (SERT) binding. However, it is
      still unclear at what time point after injection SPECT should be performed for
      optimal assessment of SERT with(123)I-FP-CIT. Therefore, we examined the time
      course of extrastriatal (123)I-FP-CIT binding. METHODS: Nineteen healthy, male
      subjects were included, and SPECT images were acquired up to 3 h after (123)I-FP
      CIT injection. Region-of-interest analysis was performed, and specific-to
      nonspecific binding ratios were calculated. RESULTS: Specific-to-nonspecific
      (123)I-FP-CIT binding ratios in the midbrain and diencephalon were significantly
      higher 2 h after injection than 1 h after injection and remained stable between 2
      and 3 h after injection. CONCLUSION: The optimal time frame for assessing (123)I
      FP-CIT binding to extrastriatal SERT is between 2 and 3 h after injection of the
      tracer.

PMID- 22627001
TI  - Noise considerations for PET quantification using maximum and peak standardized
      uptake value.
AB  - In tumor response monitoring studies with (18)F-FDG PET, maximum standardized
      uptake value (SUV(max)) is commonly applied as a quantitative metric. Although it
      has several advantages due to its simplicity of determination, concerns about the
      influence of image noise on single-pixel SUV(max) persist. In this study, we
      measured aspects of bias and reproducibility associated with SUV(max) and the
      closely related peak SUV (SUV(peak)) using real patient data to provide a
      realistic noise context. METHODS: List-mode 3-dimensional PET data were acquired
      for 15 min over a single bed position in twenty (18)F-FDG oncology patients. For
      each patient, data were sorted so as to form 2 sets of images: respiration-gated
      images such that each image had statistical quality comparable to a 3 min/bed
      position scan, and 5 statistically independent (ungated) images of different
      durations (1, 2, 3, 4, and 5 min). Tumor SUV(max) and SUV(peak) (12-mm-diameter
      spheric region of interest positioned so as to maximize the enclosed average)
      were analyzed in terms of reproducibility and bias. The component of
      reproducibility due to statistical noise (independent of physiologic and other
      variables) was measured using paired SUVs from 2 comparable respiration-gated
      images. Bias was measured as a function of scan duration. RESULTS: Replicate
      tumor SUV measurements had a within-patient SD of 5.6% +/- 0.9% for SUV(max) and
      2.5% +/- 0.4% for SUV(peak). SUV(max) had average positive biases of 30%, 18%,
      12%, 4%, and 5% for the 1-, 2-, 3-, 4-, and 5-min images, respectively. SUV(peak)
      was also biased but to a lesser extent: 11%, 8%, 5%, 1%, and 4% for the 1-, 2-, 3
      , 4-, and 5-min images, respectively. CONCLUSION: The advantages of SUV(max) are
      best exploited when PET images have a high statistical quality. For images with
      noise properties typically associated with clinical whole-body studies, SUV(peak)
      provides a slightly more robust alternative for assessing the most metabolically
      active region of tumor.

PMID- 22627002
TI  - A score comparability study for the NBDHE: paper-pencil versus computer versions.
AB  - This study evaluated the comparability of a paper-pencil (PP) version and two
      computer-based (CB) versions of the National Board Dental Hygiene Examination.
      Comparability was evaluated by validity and psychometric criteria. Data were
      collected from the following resources: (1) 4,560 candidates enrolled in
      accredited dental hygiene programs who took the PP version in the Spring 2009,
      (2) 973 and 1,033 candidates enrolled in accredited dental hygiene programs who
      took two separate CB versions in 2009, and (3) the survey data from 2,486
      candidates who took the CB versions in 2009. The results from the PP and CB
      versions were found to be comparable on several criteria.

PMID- 22627003
TI  - Acute autonomic, sensory and motor neuropathy with oral hypoesthesia leading to
      split tongue.

PMID- 22627005
TI  - Treatment of obesity as a potential complementary approach to cancer therapy.
AB  - Obesity has long been recognized as a risk factor for diabetes and cardiovascular
      disease. Recent epidemiological data also associate obesity with cancer risk and
      progression. For this reason, a combination treatment of obesity along with
      treatment of the cancer itself may improve patient survival and well-being. As
      the molecular pathways linking obesity and cancer become better understood, new
      potential therapy targets are surfacing. In this article, we summarize the
      mechanisms proposed to account for the obesity-cancer association and discuss
      approaches to manipulation of adipose tissue as potential interventions aimed at
      cancer prevention or supplemental therapy.

PMID- 22627004
TI  - Mitochondrial inhibitor models of Huntington's disease and Parkinson's disease
      induce zinc accumulation and are attenuated by inhibition of zinc neurotoxicity
      in vitro or in vivo.
AB  - BACKGROUND: Inhibition of mitochondrial function occurs in many neurodegenerative
      diseases, and inhibitors of mitochondrial complexes I and II are used to model
      them. The complex II inhibitor, 3-nitroproprionic acid (3-NPA), kills the
      striatal neurons susceptible in Huntington's disease. The complex I inhibitor N
      methyl-4-phenylpyridium (MPP(+)) and 6-hydroxydopamine (6-OHDA) are used to model
      Parkinson's disease. Zinc (Zn(2+)) accumulates after 3-NPA, 6-OHDA and MPP(+) in
      situ or in vivo. OBJECTIVE: We will investigate the role of Zn(2+) neurotoxicity
      in 3-NPA, 6-OHDA and MPP(+). METHODS: Murine striatal/midbrain tyrosine
      hydroxylase positive, or near-pure cortical neuronal cultures, or animals were
      exposed to 3-NPA or MPP(+) and 6-OHDA with or without neuroprotective compounds.
      Intracellular zinc ([Zn(2+)](i)), nicotinamide adenine dinucleotide (NAD(+)),
      NADH, glycolytic intermediates and neurotoxicity were measured. RESULTS: We
      showed that compounds or genetics which restore NAD(+) and attenuate Zn(2+)
      neurotoxicity (pyruvate, nicotinamide, NAD(+), increased NAD(+) synthesis,
      sirtuin inhibition or Zn(2+) chelation) attenuated the neuronal death induced by
      these toxins. The increase in [Zn(2+)](i) preceded a reduction in the NAD(+)/NADH
      ratio that caused a reversible glycolytic inhibition. Pyruvate, nicotinamide and
      NAD(+) reversed the reductions in the NAD(+)/NADH ratio, glycolysis and neuronal
      death after challenge with 3-NPA, 6-OHDA or MPP(+), as was previously shown for
      exogenous Zn(2+). To test efficacy in vivo, we injected 3-NPA into the striatum
      of rats and systemically into mice, with or without pyruvate. We observed early
      striatal Zn(2+) fluorescence, and pyruvate significantly attenuated the 3-NPA
      induced lesion and restored behavioral scores. CONCLUSIONS: Together, these
      studies suggest that Zn(2+) accumulation caused by MPP(+) and 3-NPA is a novel
      preventable mechanism of the resultant neurotoxicity.

PMID- 22627006
TI  - Drug discovery in pharmaceutical industry: productivity challenges and trends.
AB  - Low productivity, rising R&D costs, dissipating proprietary products and
      dwindling pipelines are driving the pharmaceutical industry to unprecedented
      challenges and scrutiny. In this article I reflect on the current status of the
      pharmaceutical industry and reasons for continued low productivity. An emerging
      'symbiotic model of innovation', that addresses underlying issues in drug failure
      and attempts to narrow gaps in current drug discovery processes, is discussed to
      boost productivity. The model emphasizes partnerships in innovation to deliver
      quality products in a cost-effective system. I also discuss diverse options to
      build a balanced research portfolio with higher potential for persistent delivery
      of drug molecules.

PMID- 22627007
TI  - Network analysis has diverse roles in drug discovery.
AB  - Computational biologists use network analysis to uncover relationships between
      various data types of interest for drug discovery. For example, signalling and
      metabolic pathways are commonly used to understand disease states and drug
      mechanisms. However, several other flavours of network analysis techniques are
      also applicable in a drug discovery context. Recent advances include networks
      that encompass relationships between diseases, molecular mechanisms and gene
      targets. Even social networks that mirror interactions within the scientific
      community are helping to foster collaborations and novel research. We review how
      these different types of network analysis approaches facilitate drug discovery
      and their associated challenges.

PMID- 22627008
TI  - Decoding continuous three-dimensional hand trajectories from epidural
      electrocorticographic signals in Japanese macaques.
AB  - Brain-machine interface (BMI) technology captures brain signals to enable control
      of prosthetic or communication devices with the goal of assisting patients who
      have limited or no ability to perform voluntary movements. Decoding of inherent
      information in brain signals to interpret the user's intention is one of main
      approaches for developing BMI technology. Subdural electrocorticography (sECoG)
      based decoding provides good accuracy, but surgical complications are one of the
      major concerns for this approach to be applied in BMIs. In contrast, epidural
      electrocorticography (eECoG) is less invasive, thus it is theoretically more
      suitable for long-term implementation, although it is unclear whether eECoG
      signals carry sufficient information for decoding natural movements. We
      successfully decoded continuous three-dimensional hand trajectories from eECoG
      signals in Japanese macaques. A steady quantity of information of continuous hand
      movements could be acquired from the decoding system for at least several months,
      and a decoding model could be used for ~10 days without significant degradation
      in accuracy or recalibration. The correlation coefficients between observed and
      predicted trajectories were lower than those for sECoG-based decoding experiments
      we previously reported, owing to a greater degree of chewing artifacts in eECoG
      based decoding than is found in sECoG-based decoding. As one of the safest
      invasive recording methods available, eECoG provides an acceptable level of
      performance. With the ease of replacement and upgrades, eECoG systems could
      become the first-choice interface for real-life BMI applications.

PMID- 22627009
TI  - [Clinical simulation and our new reality. The need for a combined effort].

PMID- 22627010
TI  - [Septic shock secondary due to Staphylococcus aureus-induced hip arthritis:
      Treatment in the Recovery Unit].

PMID- 22627011
TI  - [Prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma
      genitalium infections in the emergency department].
AB  - STUDY OBJECTIVE: To estimate the prevalence of Chlamydia trachomatis (CT),
      Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG) in patients under 31
      years of age admitted to the emergency department of the University Hospital of
      Montpellier, for which a urinalysis was performed. PATIENTS AND METHODS: CT, NG
      and MG specific real-time PCRs were performed in the urine samples from 301
      patients between July 2010 and January 2011. RESULTS: CT DNA was detected in 11%
      of patients, NG DNA in 3.7% of patients and MG DNA in one patient. Seventy-five
      percent of male patients and only 13% of women were diagnosed with sexually
      transmitted infection (STI). No patient with leucocyturia below 10(4)/mL had a
      positive PCR result for one of the three bacteria. Of the patients with
      leucocyturia greater or equal to 10(4)/mL, CT was detected in 23.4% of men and
      11% of women, NG in 19.2% of men and 1% of women, and MG in 2.1% of men.
      CONCLUSION: The prevalence of NG and CT detection in our population was high
      while that of MG was low. The diagnosis was facilitated by the use of PCR on the
      urine sample although this sample is not recommended for the molecular detection
      of bacterial agents of STIs and may explain the low detection of MG. The study
      allowed diagnosing STIs in 14.3% of our patient population.

PMID- 22627012
TI  - Severe hypomagnesemia and hypoparathyroidism induced by omeprazole.

PMID- 22627013
TI  - Rapid isolation of single-chain antibodies from a human synthetic phage display
      library for detection of Bacillus thuringiensis (Bt) Cry1B toxin.
AB  - Single chain variable fragment antibody (scFv) is capable of binding its target
      antigens and is one of the most popular recombinant antibodies format for many
      applications. In this study, a large human synthetic phage displayed library
      (Tomlinson J) was employed to generate scFvs against Cry1B toxin by affinity
      panning. After four rounds of panning, six monoclonal phage particles capable of
      binding with the Cry1B were isolated, sequenced and characterized by Enzyme
      Linked Immunosorbent Assay (ELISA). Two of the identified novel anti-Cry1B scFvs,
      namely H9 and B12, were expressed in Escherichia coli HB2151 and purified by Ni
      metal ion affinity chromatography. Sodium dodecyl sulfate polyacrylamine gel
      electrophoresis (SDS-PAGE) indicated that the relative molecular mass of scFv was
      estimated at 30 kDa. The purified scFv-H9 was used to develop an indirect
      competitive enzyme-linked immunosorbent assay (ic-ELISA) for Cry1B toxin. The
      linear range of detection for standards in this ic-ELISA was approximately 0.19
      1.1 MUg mL-1 and 50% inhibition of control (IC50) was 0.84 MUg mL-1 for Cry1B.
      The affinity of scfv-H9 was (1.95+/-0.12) * 107 M-1 and showed cross-reactivity
      with Cry1Ab toxin and Cry1Ac toxin (8.53% and 7.58%, respectively), higher cross
      reactivity (12.8%) with Cry1C toxin. The average recoveries of Cry1B toxin from
      spiked leaf and rice samples were in the range 89.5-96.4%, and 88.5-95.6%,
      respectively, with a coefficient of variation (C.V) less than 6.0%. These results
      showed promising applications of scfv-H9 for detecting Cry1B toxin in
      agricultural and environmental samples.

PMID- 22627014
TI  - Transfer of PCBs from bottom sediment to freshwater river fish: a food-web
      modelling approach in the Rhone River (France) in support of sediment management.
AB  - Since 2005, restrictions have been because of fish consumption along the Rhone
      River because of high polychlorobiphenyl (PCB) concentrations, which have
      resulted inadverse economic consequences for professional fisheries in affected
      areas. French environmental authorities have expended considerable efforts to
      research sediment remediation strategies and development of sediment quality
      guidelines designed to protect the health of humans consuming Rhone River fish.
      Here we: (1) develop a bioaccumulation food-web model that describes PCB
      concentrations in three common freshwater fish species of the Rhone River, using
      Bayesian inference to estimate the input parameters; (2) test the predictive
      power of the model in terms of risk assessment for fish consumption; and (3)
      discuss the use of this approach to develop sediment quality guidelines that
      protect the health of humans consuming Rhone River fish. The bioaccumulation
      model predictions are protective for human consumer of fish and are efficient for
      use in risk assessment. For example, 85% of the predicted values were within a
      factor of 5 of measured CB153 concentrations in fish. Using sensitivity analyses,
      the major role played by sediment and diet behaviors on bioaccumulation process
      is illustrated: the parameters involved in the respiratory process (contamination
      from water) have little impact on model outputs, whereas the parameters related
      to diet and digestion processes are the most sensitive. The bioaccumulation model
      was applied to derive sediment concentrations compatible with safe fish
      consumption. The resulting PCB sediment thresholds (expressed as the sum of seven
      PCB indicator congeners) that are protective for the consumption of the fish
      species ranged from 0.7 to 3 ng/g (dw).

PMID- 22627015
TI  - Hematological parameters' changes in mice subchronically exposed to static
      magnetic fields of different orientations.
AB  - Static magnetic fields (SMFs) are time independent fields whose intensity can be
      spatially dependent. This study investigates influence of subchronic continuous
      exposure to upward and downward directed SMF on hematological parameters and
      spleen cellularity in mice. The experiment is performed on the Northern
      hemisphere; consequently, the vertical component of geomagnetic field is directed
      downward. Male, Swiss-Webster, 6 weeks old mice were exposed to the vertically
      declining SMF. Mice were divided in three groups and continuously exposed or not
      exposed for 28 days to the SMF characterized by the averaged field of 16 mT and
      averaged field gradient of 10 mT/cm. Differently oriented SMF did not alter
      hemoglobin and hematocrit content among the groups. However, the groups exposed
      to the upward and downward fields had statistically significant higher levels of
      serum transferrin compared to the control. Moreover, spleen cellularity in
      animals in the downward group was significantly higher compared to the upward and
      control group. In addition, spleen lymphocytes in both of the exposed groups were
      significantly higher than in the control group. In contrast, spleen granulocytes
      in the exposed groups were significantly lower than in the control group.
      Significant decrease was also observed in brain and liver iron content with
      concomitant increase of iron in serum and spleen in exposed animals. Subchronic
      continuous exposure to 16 mT SMF caused lymphocyte and granulocyte redistribution
      between spleen and blood. This distribution is typical for stress induced
      hematological changes. These results suggest that observed changes were not due
      to an unspecific stress response, but that they were rather caused by specific
      adaptation to subchronic SMF exposure.

PMID- 22627016
TI  - Leveraging the "living laboratory": on the emergence of the entrepreneurial
      hospital.
AB  - For years, scholars have debated the "commercial ethos" in higher education, and
      the rise of the entrepreneurial university. But what of the "entrepreneurial
      hospital"? Largely unnoticed by scholars, this unique organisational form differs
      from the entrepreneurial university in some significant ways, not least in its
      capacity to use its innovations, and to count patients-and even patient
      populations-amongst its human capital. Accordingly, this article provides an
      initial conceptualisation of the entrepreneurial hospital, along with an
      exploration of its larger implications. Using twenty-six semi-structured
      interviews with key-informants (2008-2009), who work in two networked
      organisations within a single academic health science system in a Canadian
      province, our analysis identifies distinctive characteristics of an
      entrepreneurial hospital. Informed by grounded theory, especially situational
      analysis, we derive from our data an illustration of potentially incommensurate
      understandings of the entrepreneurial hospital's resources. On one hand, our
      study participants view patients and patient populations as a resource for
      research, linking its value to the contribution it can make to improved, more
      cost-effective care. On the other hand, some also see commercial potential in
      this resource. In both cases, exploitation is accompanied by perceived
      obligations to make proper use of patient populations, and to "give back" to the
      public-at-large, including through the entrepreneurial search for new ways of
      mobilising the resources of publicly-funded health care. Thus, a key task of the
      entrepreneurial hospital is to invent and mediate new uses for its care
      infrastructure and the unique resource constituted by patient populations. By
      drawing together care and research in new ways, the entrepreneurial hospital
      promises increased capacity for biomedical innovation. Yet, as it invents and
      mediates new uses for patient populations and health care infrastructure, the
      entrepreneurial hospital stands to significantly redefine both systems of care
      and the bonds of social solidarity.

PMID- 22627017
TI  - Improving teamwork and safety: toward a practical systems approach, a commentary
      on Deneckere et al.

PMID- 22627018
TI  - Antibacterial effect of novel synthesized sulfated beta-cyclodextrin crosslinked
      cotton fabric and its improved antibacterial activities with ZnO, TiO2 and Ag
      nanoparticles coating.
AB  - Sulfated beta-cyclodextrin was synthesized from sulfonation of beta-cyclodextrin
      and sulfated polymer was crosslinked with cotton fabric using
      ethylenediaminetetraacetic acid as crosslinker. ZnO, TiO(2) and Ag nanoparticles
      were prepared and characterized by XRD, UV, DLS, SEM and PSA. The prepared
      nanoparticles were coated on crosslinked cotton fabric. The crosslinking and
      nanoparticles coating effects of cotton fabrics were studied by FTIR and SEM
      analysis. The antibacterial test was done against gram positive Staphylococcus
      aureus and gram negative Escherichia coli bacterium.

PMID- 22627020
TI  - Correlation between the arterial pulse wave of the cerebral microcirculation and
      CBF during breath holding and hyperventilation in human.
AB  - OBJECTIVE: To evaluate if relative changes in the amplitude of the arterial pulse
      wave of the cerebral microcirculation (APWCM) measured by near-infrared
      spectroscopy (NIRS) may provide information about relative changes of cerebral
      blood flow (CBF) in cerebral cortex. METHODS: In 10 healthy human volunteers,
      through simultaneous recording of the APWCM amplitude by means of NIRS and the
      mean blood flow velocity (MBFV) of middle cerebral artery by means of
      transcranial Doppler (TCD) at rest and during breath holding and
      hyperventilation, we evaluate a possible correlation between relative changes of
      the mean APWCM amplitude and relative changes of MBFV. RESULTS: We found a
      significant linear correlation: breath holding: R(2) 0.84, p < 0.001,
      hyperventilation: R(2) 0.81, p<0.001. CONCLUSION: The relative changes of the
      mean APWCM amplitude seem able to provide information about relative changes of
      CBF of cerebral cortex in healthy adult humans during breath holding and
      hyperventilation. SIGNIFICANCE: APWCM detected by NIRS, a safe, repeatable,
      inexpensive technology and at the bedside may improve the study of cerebral
      cortex microcirculation in neurological diseases.

PMID- 22627019
TI  - Effects of carpal tunnel syndrome on adaptation of multi-digit forces to object
      texture.
AB  - OBJECTIVE: The ability to adapt digit forces to object properties requires both
      anticipatory and feedback-driven control mechanisms which can be disrupted in
      individuals with a compromised sensorimotor system. Carpal tunnel syndrome (CTS)
      is a median nerve compression neuropathy affecting sensory and motor function in
      a subset of digits in the hand. Our objective was to examine how CTS patients
      coordinate anticipatory and feedback-driven control for multi-digit grip force
      adaptation. METHODS: We asked CTS patients and healthy controls to grasp, lift,
      and hold an object with different textures. RESULTS: CTS patients effectively
      adapted their digit forces to changes in object texture, but produced excessive
      grip forces. CTS patients also produced larger peak force rate profiles with
      fewer modulations of normal force prior to lift onset than did controls and
      continued to increase grip force throughout the lift whereas forces were set at
      lift onset for the controls. CONCLUSIONS: These findings suggest that CTS
      patients use less online sensory feedback for fine-tuning their grip forces,
      relying more on anticipatory control than do healthy controls. SIGNIFICANCE:
      These characteristics in force adaptation in CTS patients indicate impaired
      sensorimotor control which leads to excessive grip forces with the potential to
      further exacerbate their median nerve compression.

PMID- 22627021
TI  - Motor unit firing in amyotrophic lateral sclerosis and other upper and lower
      motor neurone disorders.
AB  - OBJECTIVE: Motor unit recruitment order and firing rate was investigated in
      healthy subjects, and in small numbers of patients 50years ago. We aimed to
      investigate firing rate in different disorders, testing the same target muscle
      with normal strength, to evaluate possible application in diagnosing upper motor
      neuron (UMN) lesion. METHODS: We studied motor unit firing in the tibialis
      anterior muscle in six groups of subjects; normal subjects (n=45), patients with
      amyotrophic lateral sclerosis (ALS) (n=36), primary lateral sclerosis (PLS)
      (n=21), progressive muscular atrophy (PMA) (n=14), various upper motor neurone
      lesions (n=16) and polyneuropathy (n=42). In all these subjects the tibialis
      anterior muscle was of normal strength. Motor units were recruited during slight
      contraction in order to study 2-5 motor units at each recording site, using a
      standard concentric needle electrode, so that 20-22 motor units were recorded in
      each muscle. We analysed the coefficient of variation (CV) for amplitude, area,
      duration and firing rate in these motor units, and the correlation between motor
      unit potential size and recruitment order. RESULTS: The mean MU firing rate in
      this task was similar in each group. No recruitment order was disclosed within
      the limits of the study task. The CV of firing rate was decreased in UMN and PLS
      groups. ALS patients with marked spasticity showed a lower CV of motor unit
      firing rate. The CV of amplitude, area and duration was similar between groups.
      CONCLUSIONS: These results in tibialis anterior indicate that physiological
      modulation of lower motor neuron (LMN) firing rate is decreased in patients with
      lower limb spasticity. The variability of MU discharges tends to be greater in
      diseases affecting the LMN. SIGNIFICANCE: These results suggest that,
      notwithstanding the simplicity of the task we have used, the physiological
      variability of motor unit firing may be a useful variable in assessing UMN
      involvement in motor system disorders.

PMID- 22627024
TI  - Commercial sexual exploitation of children and the school nurse.
AB  - As trusted health professionals in the school setting, school nurses are well
      positioned to identify students who may be victims of commercial sexual
      exploitation of children (CSEC). However, until recently this issue has been
      clouded by lack of awareness, stigma, and/or denial. Since nationally the average
      age of entry for girls into the commercial sex industry (specifically
      prostitution) is 12-15 years old, many of these young people continue to attend
      school although attendance may be sporadic. Additional continuing education is
      needed to increase school nurses' awareness that these young victims might be in
      their practices, whether they are located in urban, rural, or suburban
      communities. As primary sources of health care for children throughout the United
      States, school nurses have a pivotal role in helping an exploited girl move
      beyond invisibility to a path of safety and support-and a new life.

PMID- 22627022
TI  - The effects of wide pulse neuromuscular electrical stimulation on elbow flexion
      torque in individuals with chronic hemiparetic stroke.
AB  - OBJECTIVE: Neuromuscular electrical stimulation that incorporates wide pulse
      widths (1ms) and high frequencies (100Hz; wide pulse-NMES (WP-NMES)) augments
      contractions through an increased reflexive recruitment of motoneurons in
      individuals without neurological impairments and those with spinal cord injury.
      The current study was designed to investigate whether WP-NMES also augments
      contractions after stroke. We hypothesized that WP-NMES would generate larger
      contractions in the paretic arm compared to the non-paretic arm due to increased
      reflex excitability for paretic muscles after stroke. METHODS: The biceps brachii
      muscles were stimulated bilaterally in 10 individuals with chronic hemiparetic
      stroke. Four stimulation patterns were delivered to explore the effects of pulse
      width and frequency on contraction amplitude: 20-100-20Hz (4s each phase, 1ms
      pulse width); 20-100-20Hz (4s each phase, 0.1ms); 20Hz for 12s (1ms); and 100Hz
      for 12s (1ms). Elbow flexion torque and electromyography were recorded. RESULTS:
      Stimulation that incorporated 1ms pulses evoked more torque in the paretic arm
      than the non-paretic arm. When 0.1ms pulses were used there was no difference in
      torque between arms. For both arms, torque declined significantly during the
      constant frequency 100Hz stimulation and did not change during the constant
      frequency 20Hz stimulation. CONCLUSIONS: The larger contractions generated by WP
      NMES are likely due to increased reflexive recruitment of motoneurons, resulting
      from increased reflex excitability on the paretic side. SIGNIFICANCE: NMES that
      elicits larger contractions may allow for development of more effective stroke
      rehabilitation paradigms and functional neural prostheses.

PMID- 22627023
TI  - Mass spectrometric elucidation of the neuropeptidome of a crustacean
      neuroendocrine organ.
AB  - The blue crab Callinectes sapidus has been used as an experimental model organism
      for the study of regulation of cardiac activity and other physiological
      processes. Moreover, it is an economically and ecologically important crustacean
      species. However, there was no previous report on the characterization of its
      neuropeptidome. To fill in this gap, we employed multiple sample preparation
      methods including direct tissue profiling, crude tissue extraction and tissue
      extract fractionation by HPLC to obtain a complete description of the
      neuropeptidome of C. sapidus. Matrix-assisted laser desorption/ionization (MALDI)
      Fourier transform mass spectrometry (FTMS) and MALDI-time-of-flight (TOF)/TOF
      were utilized initially to obtain a quick snapshot of the neuropeptide profile,
      and subsequently nanoflow liquid chromatography (nanoLC) coupled with
      electrospray ionization quadrupole time-of-flight (ESI-Q-TOF) tandem MS analysis
      of neuropeptide extracts was conducted for de novo sequencing. Simultaneously,
      the pericardial organ (PO) tissue extract was labeled by a novel N,N-dimethylated
      leucine (DiLeu) reagent, offering enhanced fragmentation efficiency of peptides.
      In total, 130 peptide sequences belonging to 11 known neuropeptide families
      including orcomyotropin, pyrokinin, allatostatin A (AST-A), allatostatin B (AST
      B), FMRFamide-like peptides (FLPs), and orcokinin were identified. Among these
      130 sequences, 44 are novel peptides and 86 are previously identified. Overall,
      our results lay the groundwork for future physiological studies of neuropeptides
      in C. sapidus and other crustaceans.

PMID- 22627025
TI  - Eye movements during object recognition in visual agnosia.
AB  - This paper reports the first ever detailed study about eye movement patterns
      during single object recognition in visual agnosia. Eye movements were recorded
      in a patient with an integrative agnosic deficit during two recognition tasks:
      common object naming and novel object recognition memory. The patient showed
      normal directional biases in saccades and fixation dwell times in both tasks and
      was as likely as controls to fixate within object bounding contour regardless of
      recognition accuracy. In contrast, following initial saccades of similar
      amplitude to controls, the patient showed a bias for short saccades. In object
      naming, but not in recognition memory, the similarity of the spatial
      distributions of patient and control fixations was modulated by recognition
      accuracy. The study provides new evidence about how eye movements can be used to
      elucidate the functional impairments underlying object recognition deficits. We
      argue that the results reflect a breakdown in normal functional processes
      involved in the integration of shape information across object structure during
      the visual perception of shape.

PMID- 22627026
TI  - Shared features of S100B immunohistochemistry and cytochrome oxidase
      histochemistry in the ventroposterior thalamus and lateral habenula in neonatal
      rats.
AB  - The ventroposterior thalamus and the habenular nuclei of the epithalamus are
      relevant to the monoaminergic system functionally and anatomically. The glia
      derived S100B protein plays a critical role in the development of the nervous
      system including the monoaminergic systems. In this study, we performed an
      immunohistochemical study of glia-related proteins including S100B, serotonin
      transporter, and microtubule-associated protein 2, as well as cytochrome oxidase
      histochemistry in neonatal rats. Results showed the same findings for S100B
      immunohistochemistry between the ventroposterior thalamus and the lateral
      habenula at postnatal day 7: intense staining in cell bodies of astrocytes,
      diffusely spread immunoproduct in the intercellular space, and S100B-free areas
      as well as a strong reaction to cytochrome oxidase histochemistry. Further common
      features were the scarcity of glial fibrillary acidic protein-positive astrocytes
      and the few apoptotic cells observed. The results of the cytochrome oxidase
      reaction suggested that S100B is released actively into intercellular areas in
      restricted brain regions showing high neuronal activity at postnatal day 7.
      Pathology of the ventroposterior thalamus and the habenula is suggested in mental
      disorders, and S100B might be a key factor for investigations in these areas.

PMID- 22627027
TI  - Blinded and uniform cause of death verification in a lung cancer CT screening
      trial.
AB  - Disease-specific mortality is the final outcome of a lung cancer screening trial,
      therefore cause of death verification is crucial. The use of death certificates
      for this purpose is debated because of bias, inaccurate completion and incorrect
      ante mortem diagnoses. A cause of death evaluation process was designed to ensure
      a uniform and unbiased determination of the graduation of certainty that lung
      cancer was the underlying cause of death. An independent clinical expert
      committee will review the medical files of all deceased participants once
      diagnosed with lung cancer and will make use of a flow chart and predetermined
      criteria. A pilot study of fifty cases was conducted to determine the performance
      of this process and to compare the outcome with the official death certificates.
      The independent review has shown an agreement of 90% (kappa 0.65), which
      demonstrates a uniform classification. The sensitivity and specificity of the
      death certificates for lung cancer specific mortality were 95.2 and 62.5%. This
      demonstrates a limited distinctive character of the death certification process
      in lung cancer patients. Our results imply that the final outcome of a lung
      cancer screening trial cannot reliably be established without predetermined
      criteria and an independent review of blinded cases.

PMID- 22627028
TI  - Genome size evolution: sizing mammalian genomes.
AB  - The study of genome size (GS) and its variation is so fascinating to the
      scientific community because it constitutes the link between the present-day
      analytical and molecular studies of the genome and the old trunk of the holistic
      and synthetic view of the genome. The GS of several taxa vary over a broad range
      and do not correlate with the complexity of the organisms (the C-value paradox).
      However, the biology of transposable elements has let us reach a satisfactory
      view of the molecular mechanisms that give rise to GS variation and novelties,
      providing a less perplexing view of the significance of the GS (C-enigma). The
      knowledge of the composition and structure of a genome is a pre-requisite for
      trying to understand the evolution of the main genome signature: its size. The
      radiation of mammals provides an approximately 180-million-year test case for
      theories of how GS evolves. It has been found from data-mining GS databases that
      GS is a useful cyto-taxonomical instrument at the level of orders/superorders,
      providing genomic signatures characterizing Monotremata, Marsupialia, Afrotheria,
      Xenarthra, Laurasiatheria, and Euarchontoglires. A hypothetical ancestral
      mammalian-like GS of 2.9-3.7 pg has been suggested. This value appears compatible
      with the average values calculated for the high systematic levels of the extant
      Monotremata (~2.97 pg) and Marsupialia (~4.07 pg), suggesting invasion of mobile
      DNA elements concurrently with the separation of the older clades of Afrotheria
      (~5.5 pg) and Xenarthra (~4.5 pg) with larger GS, leaving the Euarchontoglires
      (~3.4 pg) and Laurasiatheria (~2.8 pg) genomes with fewer transposable elements.
      However, the paucity of GS data (546 mammalian species sized from 5,488 living
      species) for species, genera, and families calls for caution. Considering that
      mammalian species may be vanished even before they are known, GS data are sorely
      needed to phenotype the effects brought about by their variation and to validate
      any hypotheses on GS evolution in mammals.

PMID- 22627029
TI  - Skeletal muscle fatigue--regulation of excitation-contraction coupling to avoid
      metabolic catastrophe.
AB  - ATP provides the energy in our muscles to generate force, through its use by
      myosin ATPases, and helps to terminate contraction by pumping Ca(2+) back into
      the sarcoplasmic reticulum, achieved by Ca(2+) ATPase. The capacity to use ATP
      through these mechanisms is sufficiently high enough so that muscles could
      quickly deplete ATP. However, this potentially catastrophic depletion is avoided.
      It has been proposed that ATP is preserved not only by the control of metabolic
      pathways providing ATP but also by the regulation of the processes that use ATP.
      Considering that contraction (i.e. myosin ATPase activity) is triggered by
      release of Ca(2+), the use of ATP can be attenuated by decreasing Ca(2+) release
      within each cell. A lower level of Ca(2+) release can be accomplished by control
      of membrane potential and by direct regulation of the ryanodine receptor (RyR,
      the Ca(2+) release channel in the terminal cisternae). These highly redundant
      control mechanisms provide an effective means by which ATP can be preserved at
      the cellular level, avoiding metabolic catastrophe. This Commentary will review
      some of the known mechanisms by which this regulation of Ca(2+) release and
      contractile response is achieved, demonstrating that skeletal muscle fatigue is a
      consequence of attenuation of contractile activation; a process that allows
      avoidance of metabolic catastrophe.

PMID- 22627030
TI  - Reversible 'anterior' leukoencephalopathy syndrome in an elderly hypertensive
      patient.

PMID- 22627031
TI  - RANKL in the osteolysis of AES total ankle replacement implants.
AB  - Peri-implant tissue reactions in failed total ankle replacement (TAR) are
      characterized by early developing peri-implant osteolysis. The hypothesis of the
      study was that this reaction is mediated by receptor activator of nuclear factor
      kappa B ligand (RANKL). Samples of peri-prosthetic tissues from failed TAR
      implants were stained for macrophages, RANKL, its receptor RANK and
      osteoprotegerin (OPG), and compared to control samples. The failed TAR implants
      were surrounded by implant capsule, synovial lining-like interface membrane or
      necrotic tissues. Infiltrating scavenger receptor I positive CD163(+) macrophages
      were frequent, in particular around necrotic soft tissues or bone sequestrate,
      and possibly in part formed due to ischemia and mechanical factors. In contrast,
      implant-derived wear debris was scanty. Still many RANK(+) macrophages were often
      seen in close contact with RANKL(+) mesenchymal cells, whereas OPG was mostly
      located at a distance in vascular endothelial cells. Foreign body giant cells
      were frequent. RANKL seems to stimulate locally accumulated CD163(+) RANK
      expressing cells to fusion, which leads to the local formation of multinuclear
      foreign body giant cells (and probably of osteoclasts). Therefore, peri-implant
      osteolysis in early TAR implant failure seems to be caused by the RANKL-driven
      chronic foreign body inflammation directed against, not implant-derived
      particles, but against necrotic autologous tissues.

PMID- 22627036
TI  - Embryonic pretreatment with bromodeoxyuridine blocks regeneration and functional
      recovery from perinatal medial frontal lesions in rats.
AB  - Removal of the midline frontal cortex on postnatal day 10 is followed by apparent
      regeneration of the part of the lost cortex, correlated with substantial recovery
      of function in adulthood. The spontaneous regrowth of the medial frontal cortex
      after midline frontal lesions on postnatal day 10 was blocked by pretreatment
      with bromodeoxyuridine (BrdU) on embryonic days 11, 12, 13, 15, or 17. BrdU
      pretreatment on embryonic day 21 or postnatal day 10 did not block either
      functional recovery or cortical regrowth. These results demonstrate a
      teratological effect of BrdU and are consistent with the claim that functional
      recovery after midline frontal removal on postnatal day 10 is supported by the
      generation of new midline frontal tissue.

PMID- 22627037
TI  - The challenge of diagnosing atypical exanthems: a clinico-laboratory study.
AB  - BACKGROUND: Although atypical exanthems pose a severe diagnostic challenge, they
      have not been studied widely. OBJECTIVE: To identify the clinical features,
      laboratory parameters and other characteristics that help establish the etiology
      of atypical exanthems. METHODS: We collected the following information from 260
      consecutive patients with atypical exanthems, including 108 children and 152
      adults: demographic data, exanthem and enanthem morphology, clinical symptoms,
      month of outbreak and total duration. Throat, rectal, and vesicle swabs as well
      as urine and skin samples were examined for bacterial and viral signs. Serologic
      studies were performed for the most common infectious agents. RESULTS: Seven
      morphological patterns were identified: macular erythema, papular erythema,
      macular-papular erythema, erythematovesicular, macular-papular erythema with
      petechiae, erythema with pustules, and urticarial. Ninety-four cases were due to
      viruses, 38 to bacteria, 65 to drugs, 3 to parasites, and one to viruses-plus
      drugs. Nineteen of the 25 cases with a petechial pattern had an infectious
      etiology (12 viral and 7 bacterial) and only 4 were iatrogenic. Sixty-one of 69
      patients with enanthems were infectious (57 viral and 4 bacterial), 6 were
      iatrogenic, and 2 remained undiagnosed. The petechial pattern was infectious in
      80% of cases (14 viral and 2 bacterial). Four cases were iatrogenic. During the
      spring and summer, 60% of exanthems were infectious and 21% were iatrogenic.
      Picornavirus infections exhibited summer prevalence (57%), peaking in July.
      LIMITATIONS: There were a variable number of patients with each of the
      morphological patterns. CONCLUSIONS: Morphological patterns, seasonal occurrence,
      and enanthem are key for etiological diagnosis of atypical exanthems.

PMID- 22627038
TI  - Clinical and histopathologic review of Schnitzler syndrome: the Mayo Clinic
      experience (1972-2011).
AB  - BACKGROUND: Schnitzler syndrome is a rare multisystem disorder, defined by
      urticaria and monoclonal gammopathy, that is associated with malignancy.
      Considered a neutrophilic urticarial dermatosis, previous reports have included
      patients with leukocytoclastic vasculitis. OBJECTIVE: We sought to better define
      the clinical features, histopathology, and outcomes of Schnitzler syndrome.
      METHODS: We retrospectively reviewed clinical records and cutaneous
      histopathology of all patients with Schnitzler syndrome seen at our institution
      from January 1, 1972, through July 31, 2011. RESULTS: Of the 20 patients
      identified, 80% had IgM kappa monoclonal gammopathy; others had IgG lambda (10%),
      IgG kappa (5%), or IgM kappa+lambda (5%). Patients had fevers (85%), arthralgias
      (70%), leukocytosis (70%), increased erythrocyte sedimentation rate (70%), bone
      pain (50%), lymphadenopathy (40%), and organomegaly (5%); 45% developed a
      hematologic malignancy. Histopathologic examination (n = 14) showed predominantly
      neutrophilic perivascular and interstitial inflammation (57%) or predominantly
      mononuclear cell perivascular inflammation (29%), with eosinophils in 50% of
      cases. None showed leukocytoclastic vasculitis. LIMITATIONS: Our study was
      limited by its retrospective design. CONCLUSION: We added 20 patients to
      approximately 100 reported cases of Schnitzler syndrome. Neutrophilic urticarial
      dermatosis was the most common histopathologic pattern, but mononuclear cells
      were predominant in many cases and the infiltrates often contained eosinophils. A
      high index of suspicion and careful clinicopathologic correlation are needed to
      avoid diagnostic delays in this syndrome associated with hematologic malignancy.

PMID- 22627039
TI  - Permethrin and malathion resistance in head lice: results of ex vivo and
      molecular assays.
AB  - BACKGROUND: Treatment of head lice infestation relies on the application of
      topical insecticides. Overuse of these products has led to the emergence of
      resistance to pyrethroids and malathion worldwide. Permethrin resistance in head
      lice is mostly conferred by the knockdown resistance (kdr) trait. OBJECTIVE: To
      evaluate the occurrence of permethrin- and malathion-resistant head lice in
      Paris. METHODS: A prospective survey was conducted in 74 elementary schools. Live
      lice collected on schoolchildren were randomly selected and submitted to ex vivo
      bioassays or underwent individual DNA extraction. A fragment of kdr-like gene was
      amplified and compared with wild-type sequences. RESULTS: Live head lice were
      detected in 574 children. Ex vivo assays showed no surviving lice after a 1-hour
      contact with malathion while most lice died after a 1-hour exposure to permethrin
      and piperonyl butoxide (85.7%, 95% confidence interval [CI]: 83.9-87.5). Among
      the 670 lice with workable DNA sequences, 661 lice (98.7%, 95% CI 97.7-99.3) had
      homozygous kdr mutations. LIMITATIONS: The findings of this large-scale survey of
      the occurrence of insecticide-resistant head lice indicated a major insecticide
      pressure in the study population, but it was not sufficient to draw conclusions
      about other populations. The presence of T917I-L920F mutations in kdr gene may
      not correlate with treatment failure in prospective studies. CONCLUSION: The high
      occurrence of kdr mutant allele suggests that insecticide resistance was already
      strongly established in the studied population. This finding must be interpreted
      with caution as it may not be predictive of treatment failure.

PMID- 22627040
TI  - Human papillomavirus in non-small-cell lung cancer: the impact of EGFR mutations
      and the response to erlotinib.
AB  - It has been suggested that human papillomavirus (HPV) could participate in the
      development of non-small-cell lung cancer (NSCLC). A higher HPV infection rate
      has been reported in the NSCLC samples from Asian non-smoker patients, with
      adenocarcinomas or responders to EGFR tyrosine kinase inhibitors (EGFR-TKI). We
      explored a potential relationship between EGFR mutation, response to EGFR-TKI and
      HPV infection in Western NSCLC patients. We retrospectively analyzed 40 NSCLC
      samples and the impact of age, gender, histology, tobacco habit and sample type.
      HPV infection rate was 2.5% and it was not statistically modified by any analyzed
      variable, although the limited sample size did not provide definitive
      conclusions. The rate of HPV infection in NSCLC should be studied in patients
      with EGFR mutations or a tendency towards presenting them.

PMID- 22627042
TI  - The effects of aminoguanidine on retinopathy in STZ-induced diabetic rats.
AB  - BACKGROUND: The accumulation of advanced glycated end products (AGEs) in retinal
      blood vessels is one of the major etiological factors contributing to diabetic
      retinopathy. Aminoguanidine (AG) is one of the most extensively used inhibitors
      of AGEs formation. The aim of this study was to investigate whether AG could
      protect the development of diabetic retinopathy through inhibition of AGEs.
      METHODS: Rat diabetes was induced by intraperitoneal injection with
      streptozotocin (STZ). AG was given to rats in drinking water. Retina was
      extracted 3 and 6 months following STZ and AG administration. Immunochemistry and
      transmission electron microscope were used to detect the expression of AGEs and
      retina morphology. RESULTS: Extensive staining of AGEs was detected in retinal
      blood vessels of 3- and 6-month diabetic rats, while no significant staining was
      found in the control non-diabetic retina or AG treated groups. Pericyte loss,
      endothelial cell proliferation, increased ratio of endothelial cells/pericytes,
      acellular capillaries and capillary occlusion were observed in the retina of 6
      month diabetic rats. The increased electron density of retinal capillary basement
      membrane, mitochondrial swelling in pericytes and endothelial cells were also
      found in 6-month diabetic rats. The 3-month diabetic rats and the AG-treated rats
      did not have similar morphological changes compared to control group. The AGEs
      staining in AG-treated rats was still weakly positive. CONCLUSIONS: AGEs plays
      pivotal roles in diabetic retinopathy. AGE deposition occurs prior to retinal
      microvasculature changes. AG could prevent the onset and development of diabetic
      retinopathy through inhibition of AGEs.

PMID- 22627041
TI  - Discovery of novel sulfonated small molecules that inhibit vascular tube
      formation.
AB  - Tumor-associated angiogenesis is a complex process that involves the interplay
      among several molecular players such as cell-surface heparan sulfate
      proteoglycans, vascular endothelial growth factors and their cognate receptors.
      PI-88, a highly sulfonated oligosaccharide, has been shown to have potent anti
      angiogenic activity and is currently in clinical trials. However, one of the
      major drawbacks of large oligosaccharides such as PI-88 is that their synthesis
      often requires numerous complex synthetic steps. In this study, several novel
      polysulfonated small molecule carbohydrate mimetics, which can easily be
      synthesized in fewer steps, are identified as promising inhibitors of
      angiogenesis in an in vitro tube formation assay.

PMID- 22627043
TI  - The influence of folate and methionine on intestinal tumour development in the
      Apc(Min/+) mouse model.
AB  - Folate and methionine are critical for one-carbon metabolism impacting DNA
      synthesis, repair, and methylation processes, as well as polyamine synthesis.
      These micronutrients have been implicated in colorectal cancer risk. There are,
      however, inconsistencies within the literature, with some studies showing
      restriction to have tumour-inhibitory effects, whereas others suggest excess to
      have adverse outcomes. We conducted a review of the published data to examine the
      accumulated evidence for involvement of dietary folate and/or methionine
      restriction or excess in intestinal tumour development in the Apc(Min/+) mouse
      model, which is genetically prone to develop such cancers. Thirteen publications
      were selected for evaluation based on the following inclusion criteria: (i) use
      of Apc(Min/+) mouse model; (ii) interventions using dietary folate and/or
      methionine; and (iii) primary outcome measures focused on intestinal tumour
      development. We found that nutritional modulation of folate and methionine was
      shown to have different effects on intestinal cancer in the Apc(Min/+) mouse,
      depending on the dosage, duration and timing of intervention, and interaction of
      the Apc(Min/+) genotype with other genetic factors affecting folate and DNA
      methylation metabolism. Although some studies showed that folate deficiency
      before tumorigenesis tended to increase risk of tumour formation, there are
      inconsistencies regarding whether excess folate post-weaning or after tumour
      initiation increases intestinal tumour burden. Altogether, the pooled data do not
      appear to indicate a difference in effect on intestinal tumour incidence between
      post-weaning diets that are folate deficient or folate adequate. The Apc(Min/+)
      mouse is a useful model for assessment of the impact of dietary folate on
      intestinal tumour development, but further research is required to understand the
      reasons for these inconsistencies amongst studies based on likely mechanisms,
      including modulation of nucleotide synthesis, DNA methylation, and chromosomal
      instability, which may affect the rate of cellular division and its control.

PMID- 22627044
TI  - Mutational analysis of the feline CLN3 gene and an ultrastructural evaluation of
      lysosomal storage materials in a cat with neuronal ceroid lipofuscinosis: an
      investigation into the molecular basis of the disease.
AB  - Neuronal ceroid lipofuscinosis (NCL) is a neurodegenerative disease caused by a
      number of different genes. A mutational analysis of the feline CLN3 gene was
      performed in a cat with NCL that had vacuolated lymphocytes, which is a feature
      of human NCL caused by defects of the CLN3 gene. To determine the candidate
      gene(s) responsible for this case, NCL-specific ultrastructures of storage
      materials were analysed. A sequence analysis indicated that the CLN3 gene was not
      likely to be responsible for this case of feline NCL because no deleterious
      mutation was detected. An ultrastructural analysis did not reveal any candidate
      gene because of inconsistency with any pattern found in human NCL. These findings
      suggest that the diagnostic criteria for human NCL are not directly applicable to
      feline NCL.

PMID- 22627045
TI  - Antibiotic resistance of Streptococcus agalactiae from cows with mastitis.
AB  - The aim of this study was to characterise the phenotypic and genotypic antibiotic
      resistance patterns of Streptococcus agalactiae isolated from cows with mastitis
      in China. Antibiotic resistance was based on minimum inhibitory concentrations
      and detection of resistance genes by PCR. S. agalactiae isolates most frequently
      exhibited phenotypic resistance to tetracycline, while the resistance genes most
      frequently detected were ermB, tetL and tetM. Resistance genes were detected in
      some susceptible isolates, whereas no resistance genes could be detected in some
      resistant isolates, indicating that the resistance genotype does not accurately
      predict phenotypic resistance.

PMID- 22627046
TI  - Gene and protein expression of cartilage canal and osteochondral junction
      chondrocytes and full-thickness cartilage in early equine osteochondrosis.
AB  - The objective of this study was to investigate the expression of several
      regulatory factors associated with cartilage maturation in horses with early
      osteochondrosis (OC) compared to normal controls. The hypothesis was that
      expression levels of Indian hedgehog (Ihh), parathyroid hormone-related peptide
      (PTH-rP), vascular endothelial growth factor (VEGF), platelet-derived growth
      factor-A (PDGF-A), and matrix metalloproteinase-13 and -3 (MMP-13, -3) would be
      increased in OC. Articular cartilage and osteochondral samples were collected
      from the femoropatellar joints from seven OC and eight normal young (1-6 months)
      horses after euthanasia and snap frozen or suspended in 4% paraformaldehyde.
      Laser capture microdissection was used to capture cells surrounding cartilage
      canals and the osteochondral junction. Total RNA was isolated from whole
      cartilage and laser-captured cells. Equine-specific Ihh, PTH-rP, VEGF, PDGF-A,
      MMP-13, and MMP-3 mRNA expression levels were evaluated by real-time (RT)-PCR.
      Spatial tissue protein expression was determined by immunohistochemistry. In
      laser-captured samples, there was significantly increased MMP-13 and PDGF-A gene
      expression in chondrocytes adjacent to cartilage canals and increased PDGF-A gene
      expression in osteochondral junction chondrocytes of OC-affected foals. In full
      thickness cartilage samples, there was significantly increased Ihh, MMP-3, and
      MMP-13 gene expression in OC samples, while PTH-rP protein expression was
      significantly higher along the osteochondral junction. The results suggest that
      pathways involving cartilage maturation and ossification are altered in early OC
      and may be associated with disease pathogenesis.

PMID- 22627047
TI  - Frequency of bovine congenital pseudomyotonia carriers in selected Italian
      Chianina sires.
AB  - Bovine congenital pseudomyotonia (PMT) is a genetic disease in Chianina and other
      breeds of cattle that induces muscular stiffness. PMT in the Chianina breed is
      caused by a missense mutation in exon 6 of the ATP2A1 gene, which encodes the
      SERCA1 pump. In this study, the prevalence of PMT carriers and the frequency of
      the deleterious PMT allele in selected subpopulations of the Chianina breed were
      estimated. The prevalence of PMT carriers among ranked Chianina sires used for
      artificial insemination in the years 2007-2011 was 13.6%. The frequency of PMT
      carriers in young bull calves born in the period January 2007 to June 2011
      selected for a performance testing programme was 13.4%. Selective breeding
      against this genetic defect is restricted to males only and therefore is
      predicted to require at least seven generations to eradicate PMT.

PMID- 22627048
TI  - Further investigation of exposure to Lawsonia intracellularis in wild and feral
      animals captured on horse properties with equine proliferative enteropathy.
AB  - This study investigated the exposure to Lawsonia intracellularis in wild birds,
      mice, rabbits, raccoons, coyotes and squirrels, and feral cats and pigs on 10
      farms with confirmed equine proliferative enteropathy (EPE). Serum samples from
      all resident foals (417 samples) as well as fecal (461) and serum (106) samples
      from wild and feral animals were collected for serological and molecular
      detection of L. intracellularis following the diagnosis of EPE in index cases. A
      total of three cats from two farms, three mice from two farms and eight
      cottontail rabbits from one farm had evidence of prior exposure to L.
      intracellularis. These animals may be an indicator of environmental exposure or
      may be actively involved in the transmission of L. intracellularis to foals by
      acting as a potential reservoir/amplifier host.

PMID- 22627049
TI  - Candida tropicalis biofilms: effect on urinary epithelial cells.
AB  - Candida tropicalis infection is strongly associated with the presence of biofilms
      in urinary catheters. Thus, the aim of this work was to study the behaviour of C.
      tropicalis in biofilms of different ages (24-120 h) formed in artificial urine
      (AU) and their effect in human urinary bladder cells (TCC-SUP). Reference strain
      ATCC 750 and two isolates from patients with candiduria (U69 and U75) were used
      in this study. The adhesion to human cells was evaluated after 2 h of contact
      with Candida biofilms, using the Crystal violet staining method, and the human
      cells response was evaluated in terms of activity inhibition and cell damage.
      Candida tropicalis aspartyl proteinase (SAPT) gene expression was determined by
      real-time PCR. Candida tropicalis biofilm cells were able to adhere to TCC-SUP
      cells. The highest extent of yeast attachment was obtained for the 72 h old
      biofilm cells. Yeasts affected TCC-SUP cells, with 120 h-biofilm cells causing
      the highest levels of cell injury. Generally, SAPT3 was highly expressed and
      SAPT4 was only detected in the reference strain. Overall, it is important to
      highlight that C. tropicalis cells detached from biofilms are able to colonize
      human cells and cause some injury and reduction of metabolic activity.

PMID- 22627050
TI  - Metabolic profiling and identification of the genetic varieties and agricultural
      origin of Cnidium officinale and Ligusticum chuanxiong.
AB  - Quality control methods for Cnidium officinale and Ligusticum chuanxiong are
      lacking because their quality is influenced by multiple factors. Thus, there is a
      need to develop a multifactorial method for measuring quality that is both
      standardized and practical. Here, we report a profiling method based on gas
      chromatography-mass spectrometry (GC-MS) to discriminate among the genetic
      varieties and agricultural origins of C. officinale and L. chuanxiong. Our
      metabolome analysis identified 68 metabolites, 13 of which were newly identified
      in our samples. The S-plot of the OPLS discriminant analysis enabled us to
      determine significant biomarkers. Using only double-compound biomarkers, the
      samples were successfully classified into distinct groups defined by genetic
      variety and cultivation origin. This method will simplify the process of
      searching for quality control markers that can be used to determine genetic
      variety and agricultural origin.

PMID- 22627051
TI  - Using crude glycerol and thin stillage for the production of microbial lipids
      through the cultivation of Rhodotorula glutinis.
AB  - Single cell oils (SCO) produced from oleaginous microorganisms are a potential
      alternative oil feedstock for biodiesel production. The worldwide production of
      glycerol, a 10% (w/w) byproduct produced in the transesterfication process of
      oils converted to biodiesel, is increasing as more biodiesel is being produced.
      For the purposes of cost reduction, crude glycerol was regarded as a suitable
      carbon source for the cultivation of Rhodotorula glutinis. In addition to using
      renewable crude glycerol, waste solution collected from the brewing company
      (called thin stillage) was adopted as a substitute to replace a costly nitrogen
      source used in the medium. The results of using mixture of crude glycerol and
      thin stillage indicated about a 27% increase in total biomass as compared to that
      of using crude glycerol with a standard medium. Using glycerol instead of glucose
      as the carbon source could also alter the lipid profile, resulting in an increase
      in linolenic acid (C18:2) to comprise over 20% of the total lipid. Successfully
      using renewable crude glycerol and thin stillage for the cultivation of
      oleaginous microorganisms could greatly enhance the economic competition of
      biodiesel produced from SCO.

PMID- 22627052
TI  - Investigation of utilization of the algal biomass residue after oil extraction to
      lower the total production cost of biodiesel.
AB  - In this study, component analysis of a novel biodiesel-producing alga,
      Pseudochoricystis ellipsoidea, was performed. The component analysis results
      indicated that proteins and amino acids are abundant in P. ellipsoidea while the
      sugar content is relatively low. Rather than its use as a carbon source, the use
      of the algal biomass residue after oil extraction as a nutrient source provided a
      new way for lowering the total production cost of biodiesel. In both lactic acid
      and ethanol fermentations, the use of the residue instead of high-cost nutrient
      yeast extract allowed a significant saving, showing the promise of the algal
      biomass residue for use as a fermentation nutrient source.

PMID- 22627053
TI  - Persistent abdominal pain caused by an inferior vena cava filter protruding into
      the duodenum and the aortic wall.
AB  - Inferior vena cava (IVC) filter placement has increased dramatically over the
      past 2 decades. Symptomatic duodenal perforation by IVC filters with involvement
      of the aorta is a very rare, but challenging, complication. We report a case of
      persistent atypical right upper quadrant pain secondary to duodenal and aortic
      perforation by an IVC filter treated with cavotomy for filter removal, primary
      repair of the duodenum, and extraction of prongs from the aorta.

PMID- 22627054
TI  - [Submandibular dermoid cyst extended to the cervical region].
AB  - INTRODUCTION: Dermoid cysts of the submandibular region are rare. We report an
      exceptional case with extension to the neck. OBSERVATION: The patient presented
      with a voluminous left submandibular cystic tumor with extension to the neck and
      to floor of the mouth. Ultrasonography and CT scan contributed to the diagnosis
      and to chose the best surgical approach in case of large cyst. In our case, the
      tumor was removed using a double cervical and intraoral approach.
      Histopathological examination confirmed a dermoid cyst. DISCUSSION: We report an
      exceptional case of dermoid cyst originating from submandibular region. A double
      surgical approach was necessary for tumor resection. Tumor removal must be
      complete; the submandibular gland may be removed if necessary.

PMID- 22627055
TI  - [Composite midfacial flap vascularized by the facial artery: a preliminary
      anatomic study].
AB  - INTRODUCTION: Extended facial tissue defects are difficult to reconstruct because
      of the anatomical and functional complexity of the area. Recently, composite
      facial allotransplantation was used for reconstruction. This could be performed
      because of specific facial blood supply and its facial and maxillary anastomoses.
      Could a composite naso-labio-mental flap rely on the sole blood supply of a
      facial artery anastomosis? We performed an anatomic study of a naso-labio-mental
      composite flap vascularized by the facial artery. MATERIAL AND METHOD: The study
      relied on arteriographies made on cadaveric heads and in vivo. The following data
      was analyzed: caliber of facial and maxillary arteries, terminal branch of facial
      arteries, and vascular territories. RESULTS: Sixteen facial arteries and six
      maxillary arteries were studied. The mean facial artery caliber was 2.06 mm (1
      3.2mm). The facial artery ended in the nasal area in 68.8% of the cases. The
      latero-nasal artery was always present; it was a branch of the facial artery in
      66.7% of cases. The two facial arteries, when injected bilaterally, always
      allowed complete facial composite flap circulation. The nasal territory of the
      flap was not opacified by the homolateral facial artery in 16.7% of the cases.
      DISCUSSION: Both facial artery anastomoses are recommended as blood supply for
      composite midfacial flaps. Preoperative imaging should be used systematically to
      assess the vascular network before harvesting.

PMID- 22627056
TI  - [Pediatric keratocystic odontogenic tumor and nevoid basal cell carcinoma
      syndrome. Predictive factors for recurrence and aggressiveness].
AB  - INTRODUCTION: Keratocystic odontogenic tumors (KOT), as complications in Nevoid
      Basal Cell Carcinoma Syndrome (NBCCS), occur early (before 20 years of age) and
      are usually more aggressive. The aim of this retrospective study was to determine
      the clinical, histological, and genetic phenotype, of these lesions and to define
      predictive features of aggressiveness. PATIENTS AND METHODS: We retrospectively
      studied five patients presenting with one or several KOT with NBCCS. We collected
      their clinical, radiological, and therapeutic data, rate of recurrence or new
      localization. Anatomopathological examinations were reviewed systematically.
      Somatic PTCH, SMO and SMAD 4 sequencing were completed. RESULTS: The average age
      at diagnosis was 11.2 years. The average number of KOT was 3.2 most often located
      in the molar region. All the cysts were enucleated. Anatomopathological
      examination revealed the presence of satellite cysts and daughter cysts and
      epithelial expansion in more than 80% of cases. No somatic mutation was observed
      among KOT. DISCUSSION: KOT develop in the first 10 years, in patients presenting
      with NBCCS, and recurrence is observed in the second and third decade. KOT are
      typically aggressive and have a tendency to recur, especially in patients with
      NBCCS. Anatomopathological examination may be predictive of the lesion's
      aggressiveness. Understanding the genetic and immunological mechanisms should
      open the way for new medical treatment.

PMID- 22627057
TI  - Loteprednol etabonate suspension 0.2% administered QID compared with olopatadine
      solution 0.1% administered BID in the treatment of seasonal allergic
      conjunctivitis: a multicenter, randomized, investigator-masked, parallel group
      study in Chinese patients.
AB  - BACKGROUND: Seasonal allergic conjunctivitis (SAC) is caused by seasonal
      allergens and usually manifests as ocular itching and bulbar conjunctival
      injection (redness). Treatment options for SAC include corticosteroids and dual
      acting antihistamine and mast-cell stabilizers. OBJECTIVE: Our objective was to
      compare the efficacy and tolerability of loteprednol etabonate (LE), a C-20 ester
      based corticosteroid, with those of olopatadine, a dual-acting antihistamine mast
      cell stabilizer, in Chinese patients. METHODS: This was a multicenter,
      randomized, investigator-masked, parallel group study. Patients with acute SAC
      experiencing grade 4 ocular itching and grade 2 or higher bulbar conjunctival
      injection received either LE suspension 0.2% QID at 4-hour intervals or
      olopatadine solution 0.1% BID at 6- to 8-hour intervals bilaterally for 15 days.
      Primary efficacy end points included the change from baseline (CFB) in ocular
      itching and bulbar conjunctival injection at day 15. The primary analysis tested
      the noninferiority of LE suspension 0.2% to olopatadine solution 0.1%.
      Tolerability outcomes included the incidence of adverse events (AEs),
      biomicroscopy findings, visual acuity, and intraocular pressure. RESULTS: A total
      of 300 patients were randomly assigned, and 293 were included in the per-protocol
      population (LE, n = 147; olopatadine, n = 146). Mean (SD) CFB at day 15 in the LE
      and olopatadine treatment groups, respectively, was -3.74 (0.47) and -3.28 (0.91)
      for ocular itching and -1.91 (0.52) and -1.71 (0.59) for bulbar conjunctival
      injection. The 95% CI for the differences in CFB in ocular itching (-0.59 to 
      0.27) and bulbar conjunctival injection (-0.27 to -0.08) was less than the
      prespecified noninferiority limit of 0.3. Treatment differences in CFB were
      significantly better with LE compared with olopatadine for both end points (P <=
      0.0006). Ocular AEs were few and similar between treatment groups. There were no
      clinically significant biomicroscopy or visual acuity findings, and no patient
      experienced a clinically significant increase in intraocular pressure (>=10 mm
      Hg). CONCLUSION: Results of this investigator-masked study with Chinese patients
      suggest LE suspension 0.2% was noninferior to olopatadine solution 0.1% for the
      treatment of SAC. Both LE suspension 0.2% and olopatadine solution 0.1% were well
      tolerated. ClinicalTrials.gov identifier: NCT01435460.

PMID- 22627058
TI  - A novel compound heterozygous TACI mutation in an autosomal recessive common
      variable immunodeficiency (CVID) family.
AB  - Common variable immunodeficiency (CVID) is a primary immune disorder
      characterized by low immunoglobulin serum levels and increased susceptibility to
      infections. Underlying genetic causes are only known in less than 15% of patients
      and encompass mutations in the genes encoding for ICOS, TACI, BAFF-R, CD19, CD20,
      CD81 and MSH5. TACI is the most frequently mutated gene among CVID patients. We
      report on two pediatric Italian male siblings with hypogammaglobulinemia and
      recurrent respiratory and gastrointestinal infections in association with a novel
      compound heterozygous TACI mutation. Both patients carry the I87N/C104R mutation
      that has not been reported yet. This results in aberrant TACI expression and
      abrogates APRIL binding on EBV B cells. This study identifies a novel combined
      mutation in TNFRSF13B increasing the spectrum of TACI mutations associated with
      CVID.

PMID- 22627059
TI  - Comparative molecular cytogenetics in Cetartiodactyla.
AB  - Cetartiodactyla comprises Artiodactyla (even-toed ungulates) and Cetacea (whales,
      dolphins and porpoises). Artiodactyla is a large taxon represented by about 200
      living species ranked in 10 families. Cetacea are classified into 13 families
      with almost 80 species. Many publications concerning karyotypic relationships in
      Cetartiodactyla have been published in previous decades. Formerly, the karyotypes
      of closely related species were compared by chromosome banding. Introduction of
      molecular cytogenetic methods facilitated comparative mapping between species
      with highly rearranged karyotypes and distantly related species. Such information
      is a prerequisite for the understanding of karyotypic phylogeny and the
      reconstruction of the karyotypes of common ancestors. This study summarizes the
      data on chromosome evolution in Cetartiodactyla, mainly derived from molecular
      cytogenetic studies. Traditionally, phylogenetic relationships of most groups
      have been estimated using morphological data. However, the results of some
      molecular studies of mammalian phylogeny are discordant with traditional
      conceptions of phylogeny. Cetartiodactyls provide several examples of
      incongruence between traditional morphological and molecular data. Such cases of
      conflict include the relationships of the major clades of artiodactyls, the
      relationships among the extant families of the suborder Ruminantia or the
      phylogeny of the family Bovidae. The most unexpected aspect of the molecular
      phylogeny was the recognition that Cetacea is a deeply nested member of
      Artiodactyla. The largest living order of terrestrial hoofed mammals is the even
      toed hoofed mammals, or Artiodactyla. The artiodactyls are composed of over 190
      living species including pigs, peccaries, hippos, camels, llamas, deer,
      pronghorns, giraffes, sheep, goats, cattle and antelopes. Cetacea is an order of
      wholly aquatic mammals, which include whales, dolphins and porpoises.
      Cetartiodactyla has become the generally accepted name for the clade containing
      both of these orders.

PMID- 22627061
TI  - MicroRNA changes in rat mesentery and serum associated with drug-induced vascular
      injury.
AB  - Regulatory miRNAs play a role in vascular biology and are involved in biochemical
      and molecular pathways dysregulated during vascular injury. Collection and
      integration of functional miRNA data into these pathways can provide insight into
      pathogenesis at the site of injury; the same technologies applied to biofluids
      may provide diagnostic or surrogate biomarkers. miRNA was analyzed from mesentery
      and serum from rats given vasculotoxic compounds for 4 days. Fenoldopam, dopamine
      and midodrine each alter hemodynamics and are associated with histologic evidence
      of vascular injury, while yohimbine is vasoactive but does not cause histologic
      evidence of vascular injury in rat. There were 38 and 35 miRNAs altered in a
      statistically significant manner with a fold change of 2 or greater in
      mesenteries of fenoldopam- and dopamine-dosed rats, respectively, with 9 of these
      miRNAs shared. 10 miRNAs were altered in rats given midodrine; 6 were shared with
      either fenoldopam or dopamine. In situ hybridization demonstrated strong
      expression and co-localization of miR-134 in affected but not in adjacent
      unaffected vessels. Mesenteric miRNA expression may provide clarity or avenues of
      research into mechanisms involved in vascular injury once the functional role of
      specific miRNAs becomes better characterized. 102 miRNAs were altered in serum
      from rats with drug-induced vascular injury. 10 miRNAs were commonly altered in
      serum from dopamine and either fenoldopam or midodrine dosed rats; 18 of these
      102 were also altered in mesenteries from rats with drug-induced vascular injury,
      suggesting their possible utility as peripheral biomarkers.

PMID- 22627060
TI  - Verapamil stereoisomers induce antiproliferative effects in vascular smooth
      muscle cells via autophagy.
AB  - Calcium channel blockers (CCBs) are important in the management of hypertension
      and limit restenosis. Although CCB efficacy could derive from decreased blood
      pressure, other mechanisms independent of CCB activity also can contribute to
      antiproliferative action. To understand mechanisms of CCB-mediated
      antiproliferation, we studied two structurally dissimilar CCBs, diltiazem and
      verapamil, in cultured rat vascular smooth muscle cells (VSMC). To elucidate CCB
      independent effects, pure stereoisomers of verapamil (R-verapamil, inactive VR; S
      verapamil, active, VS) were used. The effects of CCB exposure on cell viability
      (MTT reduction), cell proliferation ((3)H-thymidine incorporation), VSMC
      morphology by light and transmission electron microscopy (TEM) and autophagy
      (LC3I/II, ATG5) were measured. In general, verapamil, VR or VS treatment alone
      (80 MUM) appreciably enhanced MTT absorbance although higher concentrations (VR
      or VS) slightly decreased MTT absorbance. Diltiazem (140 MUM) markedly decreased
      MTT absorbance (40%) at 120 h. VR or VS treatment inhibited (3)H-thymidine
      incorporation (24h) and induced cytological alterations (i.e., karyokinesis,
      enhanced perinuclear MTT deposition, accumulated perinuclear "vacuoles"). TEM
      revealed perinuclear "vacuoles" to be aggregates of highly laminated and electron
      dense vesicles resembling autophagosomes and lysosomes, respectively. Increased
      autophagosome activity was confirmed by a concentration-dependent increase in LC3
      II formation by Western blotting and by increased perinuclear LC3-GFP(+) puncta
      in verapamil-treated VSMC. Verapamil stereoisomers appeared to decrease
      perinuclear mitochondrial density. These observations indicate that
      antiproliferative effects of verapamil stereoisomers are produced by enhanced
      mitochondrial damage and upregulated autophagy in VSMC. These effects are
      independent of CCB activity indicating a distinct mechanism of action that could
      be targeted for more efficacious anti-atherosclerotic and anti-restenosis
      therapy.

PMID- 22627062
TI  - Role of Nrf2 in preventing ethanol-induced oxidative stress and lipid
      accumulation.
AB  - Oxidative stress and lipid accumulation play important roles in alcohol-induced
      liver injury. Previous reports showed that, in livers of nuclear factor erythroid
      2-related factor 2 (Nrf2)-activated mice, genes involved in antioxidant defense
      are induced, whereas genes involved in lipid biosynthesis are suppressed. To
      investigate the role of Nrf2 in ethanol-induced hepatic alterations, Nrf2-null
      mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD)
      mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with
      maximum Nrf2 activation, were treated with ethanol (5 g/kg, po). Blood and liver
      samples were collected 6h thereafter. Ethanol increased alanine aminotransferase
      and lactate dehydrogenase activities as well as thiobarbituric acid reactive
      substances in serum of Nrf2-null and wild-type mice, but not in Nrf2-enhanced
      mice. After ethanol administration, mitochondrial glutathione concentrations
      decreased markedly in Nrf2-null mice but not in Nrf2-enhanced mice. H(2)DCFDA
      staining of primary hepatocytes isolated from the four genotypes of mice
      indicates that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2
      enhanced cells than in wild-type cells. Ethanol increased serum triglycerides and
      hepatic free fatty acids in Nrf2-null mice, and these increases were blunted in
      Nrf2-enhanced mice. In addition, the basal mRNA and nuclear protein levels of
      sterol regulatory element-binding protein 1(Srebp-1) were decreased with graded
      Nrf2 activation. Ethanol further induced Srebp-1 mRNA in Nrf2-null mice but not
      in Nrf2-enhanced mice. In conclusion, Nrf2 activation prevented alcohol-induced
      oxidative stress and accumulation of free fatty acids in liver by increasing
      genes involved in antioxidant defense and decreasing genes involved in
      lipogenesis.

PMID- 22627063
TI  - QSAR model for human pregnane X receptor (PXR) binding: screening of
      environmental chemicals and correlations with genotoxicity, endocrine disruption
      and teratogenicity.
AB  - The pregnane X receptor (PXR) has a key role in regulating the metabolism and
      transport of structurally diverse endogenous and exogenous compounds. Activation
      of PXR has the potential to initiate adverse effects, causing drug-drug
      interactions, and perturbing normal physiological functions. Therefore,
      identification of PXR ligands would be valuable information for pharmaceutical
      and toxicological research. In the present study, we developed a quantitative
      structure-activity relationship (QSAR) model for the identification of PXR
      ligands using data based on a human PXR binding assay. A total of 631 molecules,
      representing a variety of chemical structures, constituted the training set of
      the model. Cross-validation of the model showed a sensitivity of 82%, a
      specificity of 85%, and a concordance of 84%. The developed model provided
      knowledge about molecular descriptors that may influence the binding of molecules
      to PXR. The model was used to screen a large inventory of environmental
      chemicals, of which 47% was found to be within domain of the model. Approximately
      35% of the chemicals within domain were predicted to be PXR ligands. The
      predicted PXR ligands were found to be overrepresented among chemicals predicted
      to cause adverse effects, such as genotoxicity, teratogenicity, estrogen receptor
      activation and androgen receptor antagonism compared to chemicals not causing
      these effects. The developed model may be useful as a tool for predicting
      potential PXR ligands and for providing mechanistic information of toxic effects
      of chemicals.

PMID- 22627064
TI  - Update on the management of hypertension for secondary stroke prevention.
AB  - High blood pressure (BP) is the strongest risk factor for stroke. It is estimated
      that almost 50% of strokes may be attributable to hypertension. Both diastolic
      and isolated systolic hypertension are important predictors of primary or
      recurrent strokes, and even minor decreases in BP can reduce the risk of stroke.
      While the primary prevention of stroke through the treatment of hypertension is
      well established, the issue of lowering BP after a stroke has been uncertain,
      particularly since this might worsen cerebral perfusion if autoregulation remains
      chronically damaged or severe carotid artery stenosis is present. Furthermore,
      there is substantial evidence to support BP lowering for prevention of a first
      stroke; however, few trials have focused on antihypertensive therapy for
      recurrent stroke prevention. In fact, currently, BP management in patients with
      strokes remains problematic, and questions such as the choice of antihypertensive
      drug and by how much to reduce BP are yet to be resolved. Recently, the American
      Heart Association and American Stroke Association published updated guidelines
      for recurrent stroke prevention, and new recommendations on BP management have
      been included. Our review presents the most recent evidence on the management of
      hypertension in patients who have had a stroke.

PMID- 22627065
TI  - Selection and characterization of cell binding and internalizing phage
      antibodies.
AB  - Many therapeutic targets are cell surface receptors, which can be challenging
      antigens for antibody generation. For many therapeutic applications, one needs
      antibodies that not only bind the cell surface receptor but also are internalized
      into the cell. This allows use of the antibody to deliver various payloads into
      the cell to achieve a therapeutic effect. Phage antibody technology has proven a
      powerful tool for the generation and optimization of human antibodies to any
      antigen. While applied to the generation of antibodies to purified proteins, it
      is possible to directly select cell binding and internalizing antibodies on
      cells. Potential advantages of this approach include: cell surface receptors are
      in native conformation on intact cells while this might not be so for recombinant
      proteins; antibodies can be selected for both cell binding and internalization
      properties; the antibodies can be used to identify their tumor associated
      antigens; and such antibodies can be used for human treatment directly since they
      are human in sequence. This review will discuss the factors that impact the
      successful selection of cell binding and internalizing antibodies. These factors
      include the cell types used for selection, the impact of different phage antibody
      library formats, and the specific selection protocols used.

PMID- 22627066
TI  - Protein-losing enteropathy and premature ovarian failure in a young woman with
      systemic lupus erythematosus.
AB  - Protein-losing enteropathy (PLE) and autoimmune oophoritis are unusual
      manifestations of systemic lupus erythematosus (SLE). Autoimmune oophoritis may
      result in menstrual disturbance and spontaneous premature ovarian failure.
      However, there is no validated examination to confirm the diagnosis and it is
      easily neglected in patients with ovarian insufficiency. A 31-year-old woman with
      SLE presented with PLE and autoimmune oophoritis during the long course of flares
      and remissions in her lupus activity. The synchronism implied the association
      between the two. Moreover, both conditions simultaneously had a good response to
      cyclosporine A (CsA) therapy.

PMID- 22627067
TI  - Precursor films in wetting phenomena.
AB  - The spontaneous spreading of non-volatile liquid droplets on solid substrates
      poses a classic problem in the context of wetting phenomena. It is well known
      that the spreading of a macroscopic droplet is in many cases accompanied by a
      thin film of macroscopic lateral extent, the so-called precursor film, which
      emanates from the three-phase contact line region and spreads ahead of the latter
      with a much higher speed. Such films have been usually associated with liquid-on
      solid systems, but in the last decade similar films have been reported to occur
      in solid-on-solid systems. While the situations in which the thickness of such
      films is of mesoscopic size are fairly well understood, an intriguing and yet to
      be fully understood aspect is the spreading of microscopic, i.e. molecularly
      thin, films. Here we review the available experimental observations of such films
      in various liquid-on-solid and solid-on-solid systems, as well as the
      corresponding theoretical models and studies aimed at understanding their
      formation and spreading dynamics. Recent developments and perspectives for future
      research are discussed.

PMID- 22627068
TI  - Improving implementation of infection control guidelines to reduce nosocomial
      infection rates: pioneering the report card.
AB  - BACKGROUND: Two detailed checklists were developed, based on published infection
      control guidelines, for daily use by infection control practitioners in
      departments and operating rooms. AIM: To assess the impact of the checklists on
      nosocomial infection rates in three hospitals over the course of one year.
      METHODS: The checklists included 20 subheadings (+/- 150 items). Project nurses
      conducted rounds in the study (but not control) departments; during each round,
      the nurses selected 15-20 items for observation, marked the checklists according
      to appropriateness of observed behaviour and provided on-the-spot corrective
      education. Rates of adherence to the checklist, antibiotic use, number of
      obtained and positive cultures, and positive staff hand and patient environment
      cultures were reported monthly as a report card to relevant personnel and
      administrators. The rate of nosocomial infections was determined in the first and
      last months. RESULTS: The baseline nosocomial infection rate was similar in the
      study and control departments: 37/345 (11%) and 26/270 (10%) respectively. In the
      last month, the rate in the study department decreased to 16/383 (4%) (P<0.01);
      in the control it decreased insignificantly to 21/248 (8%) (not significant). No
      significant trends were detected in the number of obtained cultures, positive
      cultures, or antibiotic use. Adherence to guidelines ranged from 75% to 94%
      between the hospitals (P<0.001): the overall rate increased from 80% to 91%
      (P<0.01). CONCLUSIONS: The use of checklists during the conduct of infection
      control rounds, combined with monthly reports, was associated with a significant
      decrease in nosocomial infections in study departments.

PMID- 22627070
TI  - Overutilization of post-polypectomy surveillance colonoscopy in clinical
      practice: a prospective, multicentre study.
AB  - BACKGROUND: Although the adherence to post-polipectomy recommendations is
      advocated as a quality indicator of colonoscopy programmes, prospective data on
      actual use of surveillance are lacking. AIM: To evaluate the appropriateness of
      post-polypectomy surveillance colonoscopy on a community-wide basis and to
      identify factors associated with it. METHODS: Data on consecutive post
      polypectomy surveillance examinations performed over a 4-week period in 29
      Italian endoscopy units were collected. The time interval between index and
      surveillance colonoscopy was calculated and compared to guidelines
      recommendations. Determinants of surveillance timing appropriateness were
      assessed by logistic step-wise regression. RESULTS: Of 7081 consecutive
      outpatients, 1218 (17.2%) were referred for post-polypectomy surveillance and 902
      were included into the analysis. Surveillance colonoscopy was prescribed
      correctly in 330 subjects (36.6%) and earlier than recommended by guidelines in
      490 (54.3%). Low-risk subjects had an anticipated surveillance colonoscopy more
      frequently than global cohort (67.4% vs. 54.3%, p<0.001). At multivariate
      analysis, determinants of correct surveillance timing were high-volume workload
      centres (OR 1.92; 1.41-2.63 95%CI), centres providing written recommendation on
      surveillance interval (OR 1.70; 1.18-2.58 95%CI) and surveillance examinations
      performed within the national screening programme (OR 2.62; 1.92-3.59 95%CI).
      CONCLUSIONS: In community practice, post-polipectomy surveillance colonoscopy is
      often performed earlier than recommended, especially in low-risk subjects.
      Interventions to improve adherence to guidelines and to reduce unnecessary
      examinations are needed.

PMID- 22627073
TI  - Very late stent thrombosis with newer drug-eluting stents: no longer an issue?

PMID- 22627072
TI  - Psychosocial intervention effects on adaptation, disease course and biobehavioral
      processes in cancer.
AB  - A diagnosis of cancer and subsequent treatments place demands on psychological
      adaptation. Behavioral research suggests the importance of cognitive, behavioral,
      and social factors in facilitating adaptation during active treatment and
      throughout cancer survivorship, which forms the rationale for the use of many
      psychosocial interventions in cancer patients. This cancer experience may also
      affect physiological adaptation systems (e.g., neuroendocrine) in parallel with
      psychological adaptation changes (negative affect). Changes in adaptation may
      alter tumor growth-promoting processes (increased angiogenesis, migration and
      invasion, and inflammation) and tumor defense processes (decreased cellular
      immunity) relevant for cancer progression and the quality of life of cancer
      patients. Some evidence suggests that psychosocial intervention can improve
      psychological and physiological adaptation indicators in cancer patients.
      However, less is known about whether these interventions can influence tumor
      activity and tumor growth-promoting processes and whether changes in these
      processes could explain the psychosocial intervention effects on recurrence and
      survival documented to date. Documenting that psychosocial interventions can
      modulate molecular activities (e.g., transcriptional indicators of cell
      signaling) that govern tumor promoting and tumor defense processes on the one
      hand, and clinical disease course on the other is a key challenge for
      biobehavioral oncology research. This mini-review will summarize current
      knowledge on psychological and physiological adaptation processes affected
      throughout the stress of the cancer experience, and the effects of psychosocial
      interventions on psychological adaptation, cancer disease progression, and
      changes in stress-related biobehavioral processes that may mediate intervention
      effects on clinical cancer outcomes. Very recent intervention work in breast
      cancer will be used to illuminate emerging trends in molecular probes of interest
      in the hope of highlighting future paths that could move the field of
      biobehavioral oncology intervention research forward.

PMID- 22627074
TI  - Bradyarrhythmias and conduction blocks.
AB  - Bradyarrhythmias are a common clinical finding and comprise a number of rhythm
      disorders including sinus node dysfunction and atrioventricular conduction
      disturbances. Clinical presentation varies from asymptomatic electrocardiogram
      findings (eg, during a routine examination) to a wide range of symptoms such as
      heart failure symptoms, near syncope or syncope, central nervous symptoms, or
      nonspecific and chronic symptoms such as dizziness or fatigue. Conditions
      resulting in bradyarrhythmic disorders are divided into intrinsic and extrinsic
      conditions causing damage to the conduction system. Furthermore bradyarrhythmias
      can be a normal physiologic reaction under certain circumstances. A proper
      diagnosis including a symptom-rhythm correlation is extremely important and is
      generally established by noninvasive diagnostic studies (12-lead
      electrocardiogram, Holter electrocardiogram, exercise testing, event recorder,
      implantable loop recorder). Invasive electrophysiologic testing is rarely
      required. If reversible extrinsic causes of bradyarrhythmias such as drugs (most
      often beta-blockers, glycosides and/or calcium channel blockers) or underlying
      treatable diseases are ruled out, cardiac pacing is usually the therapy of choice
      in symptomatic bradyarrhythmias. In this article of the current series on
      arrhythmias we will review the pathophysiology, diagnosis and treatment options
      of bradyarrhythmias, especially sinus node dysfunction and atrioventricular
      conduction blocks.

PMID- 22627075
TI  - Clinicopathologic features of oral squamous papilloma and papillary squamous cell
      carcinoma: a study of 197 patients from eastern China.
AB  - Oral squamous papilloma and papillary squamous cell carcinoma are 2
      clinicopathologically distinctive papillary epithelial tumors. The current study
      aims to compare the clinical and pathologic features of these oral papillary
      lesions in a patient population from eastern China. A retrospective review in a
      series of patients with clinical and pathologic diagnosis of oral squamous
      papilloma (n = 141) and papillary squamous cell carcinoma (n = 56) was conducted.
      The average age of oral squamous papilloma was 51.0 years (male-to-female ratio,
      1.82), with the palate being the predominant site. The average age of oral
      papillary squamous cell carcinoma was 63.3 years (male-to-female ratio, 1.67),
      with the gingiva being the predominant site. Multivariate analysis revealed that
      the elderly patient with papillary lesion (>=60 years) was associated with 3.09
      fold (95% confidence interval, 1.59-6.03) increased carcinoma risk compared with
      the nonelderly patient. The lesion located on the gingiva was associated with
      4.98-fold (95% confidence interval, 1.96-12.63) increased carcinoma risk compared
      with other oral sites. Collectively, clinicopathologic features of oral squamous
      papilloma and papillary squamous cell carcinoma in eastern China were elucidated.
      Elderly patients with oral papillary lesions located on the gingiva correlate
      with higher carcinoma risk. It highlights the importance of using a histologic
      examination to confirm the clinical diagnosis for any suspicious papillary
      lesions.

PMID- 22627077
TI  - Update of the evolution of breast cancer incidence in relation to hormone
      replacement therapy use in Belgium.
AB  - BACKGROUND: Several studies reported a decrease in breast cancer (BC) incidence,
      subsequent to the decrease in hormone replacement therapy (HRT) use. AIM:
      Although Belgium has one of the highest incidences of BC in Europe and one of the
      highest rates of HRT use, we were unable, in a previous study, to observe a
      significant association between BC incidence and HRT changes. In this updated
      report we added the BC data from incidence years 2007 and 2008. MATERIAL AND
      METHOD: We used European standardized incidence rates for invasive BC in the age
      class 50-69 years for Flanders (1999-2008), Brussels and Wallonia (2004-2008),
      obtained from IMS Health HRT sales data (1997-2008) for Brussels, Flanders and
      Wallonia. The association between BC incidence and HRT use was analyzed using
      generalized estimating equations (GEE) in order to take into consideration the
      dependency between the subsequent data points. RESULTS: There was a significant
      association between the invasive BC incidence rate and estimated rate of HRT
      users in the previous year: p-value<0.001. CONCLUSION: Although this study is
      hampered by a number of limitations, these data support the idea that the drop in
      BC incidence can be partly attributed to the decrease in HRT use. Since HRT
      remains the most used medication for climacteric symptoms, we encourage the
      creation of a prospective registry in Europe, collecting detailed data in various
      European countries, in order to assess the adjusted increase in BC risk
      associated with HRT, which may be population and regimen dependent.

PMID- 22627076
TI  - Comparison of methods for estimating the intraclass correlation coefficient for
      binary responses in cancer prevention cluster randomized trials.
AB  - The intraclass correlation coefficient (ICC) is a fundamental parameter of
      interest in cluster randomized trials as it can greatly affect statistical power.
      We compare common methods of estimating the ICC in cluster randomized trials with
      binary outcomes, with a specific focus on their application to community-based
      cancer prevention trials with primary outcome of self-reported cancer screening.
      Using three real data sets from cancer screening intervention trials with
      different numbers and types of clusters and cluster sizes, we obtained point
      estimates and 95% confidence intervals for the ICC using five methods: the
      analysis of variance estimator, the Fleiss-Cuzick estimator, the Pearson
      estimator, an estimator based on generalized estimating equations and an
      estimator from a random intercept logistic regression model. We compared
      estimates of the ICC for the overall sample and by study condition. Our results
      show that ICC estimates from different methods can be quite different, although
      confidence intervals generally overlap. The ICC varied substantially by study
      condition in two studies, suggesting that the common practice of assuming a
      common ICC across all clusters in the trial is questionable. A simulation study
      confirmed pitfalls of erroneously assuming a common ICC. Investigators should
      consider using sample size and analysis methods that allow the ICC to vary by
      study condition.

PMID- 22627079
TI  - Whole-lung lavage: a successful treatment for restoring acinar ventilation
      distribution in primary acquired pulmonary alveolar proteinosis.
AB  - A 51-year-old active smoker with primary acquired pulmonary alveolar proteinosis
      (PAP) diagnosed by biopsy and anti-GM-CSF antibodies was treated safely with
      whole-lung lavage (WLL). This resulted in a rapid improvement of symptoms and
      arterial blood oxygenation, but not of standard lung function parameters.
      However, we also performed the multiple-breath nitrogen washout (MBW) test to
      determine the lung clearance index (LCI) as well as indices of acinar ventilation
      heterogeneity (S(acin)) and conductive ventilation heterogeneity (S(cond)). At
      baseline, a distinct abnormality was seen for S(acin) and LCI, while S(cond) was
      at the upper limit of normal for this subject. S(acin), in particular, was in
      excess of the S(acin) abnormality corresponding to a 20-pack-year smoking
      history. Immediately after WLL, S(acin) and S(cond) both fell to within a normal
      range while LCI also decreased but remained abnormal. The S(acin) decrease was
      much greater than the S(cond) decrease, which was to be expected after 1 week of
      smoking cessation at the hospital (smoking was resumed after release from
      hospital). A follow-up visit 7 weeks after WLL revealed a spectacular improvement
      on CT scan and improvements in standard lung function. Another follow-up visit 14
      weeks after WLL showed further improvements in standard lung function, and both
      S(acin) and S(cond) remained well within the normal range, and LCI was above the
      upper limit of normal. We conclude that in this patient, removal of excess
      surfactant by WLL resulted in a restored ventilation distribution in most of the
      distal air spaces.

PMID- 22627078
TI  - Sensory and motor characterization in the postnatal valproate rat model of
      autism.
AB  - Although autism is diagnosed according to three core features of social deficits,
      communication impairments, and repetitive or stereotyped behaviors, other
      behavioral features such as sensory and motor impairments are present in more
      than 70% of individuals with autism spectrum disorders (ASD). Exposure of rat
      pups to the teratogen valproate during sensitive periods of brain development has
      been shown to elicit behavioral features associated with autism diagnosis and has
      been proposed as a valid animal model of the disorder. The purpose of this study
      was to characterize sensory and motor performance in rats postnatally treated
      with valproate. Thirty-four rat pups were injected with either valproate (150
      mg/kg) or saline on postnatal days 6-12. Auditory and tactile startle as well as
      auditory sensory gating was assessed during both the juvenile and adolescent
      stages of development; motor testing was conducted during late adolescence and
      included a sunflower seed eating task and a vermicelli handling task. Valproate
      treated rats were underresponsive to auditory stimuli, showed deficits in
      auditory sensory gating, and demonstrated impairments in motor speed and
      performance. These findings suggest that postnatal valproate treatment elicits
      sensory and motor features often seen in individuals with ASD. Further, the
      hyposensitivity seen in postnatally valproate-treated rats contrasted with
      hypersensitivity previously reported in prenatally valproate-exposed rats. This
      suggests that timing of teratogenic exposure during early brain development may
      be important to consider when investigating the neurobiological basis of
      sensorimotor impairments in ASD.

PMID- 22627080
TI  - Sleep disorders and multiple sclerosis: a clinical and polysomnography study.
AB  - BACKGROUND: Patients with multiple sclerosis (MS) report sleep disturbances (SD)
      and excessive daytime sleepiness (EDS) more frequently than the general
      population. Our objectives were to evaluate SD and EDS in MS patients and to test
      the reliability of subjective sleep questionnaires. METHODS: Demographic and
      clinical characteristics of unselected consecutive patients with MS were
      collected. Different questionnaires were used to assess quality of sleep, daytime
      sleepiness, fatigue, anxiety, depression and quality of life (QoL). Nocturnal
      polysomnography and Multiple Sleep Latency Test (MSLT) were performed in 25
      selected MS patients with fatigue and with or without EDS. RESULTS: 205 MS
      patients were enrolled. More than half of the MS patients were classified as
      'poor sleepers'. In multivariate analysis, SD were correlated with disability,
      fatigue, depression, QoL, and pain, but not with EDS. Subjective sleepiness
      evaluated with the Epworth Sleepiness Scale and SD with the Pittsburgh Sleep
      Quality Index were not correlated with the results of the objective assessments
      of vigilance (MSLT) and sleep. CONCLUSIONS: SD and EDS are frequent among MS
      patients. Objective assessment of vigilance and sleep can be challenging but MS
      patients who are poor sleepers should receive immediate assessment and treatment
      in order to improve QoL.

PMID- 22627081
TI  - Sundowning syndrome in aging and dementia: research in mouse models.
AB  - Both normal aging and dementia are associated with altered circadian regulation
      of physiology and behavior. Elderly individuals and dementia patients commonly
      experience disrupted sleep-wake cycles, which may lead to psychomotor agitation,
      confusion, and wandering. These behaviors are disruptive to both patients and
      caregivers. Sundowning syndrome, which encompasses many of these behaviors, is
      characterized by a temporal pattern in the severity of symptoms, usually
      expressed as worse during the late afternoon or evening. Other than antipsychotic
      medications, off-label medications, and restraint, few treatment options are
      available. The aim of this paper is to review mouse studies of circadian
      behavioral disturbances relevant to sundowning, in order to determine potential
      models for studying the mechanisms of sundowning syndrome. The emergence of a
      useful mouse model should facilitate the development of novel therapeutic
      approaches.

PMID- 22627082
TI  - Molecular mechanism for the selective impairment of cancer mitochondrial function
      by a mitochondrially targeted vitamin E analogue.
AB  - The effects of alpha-tocopheryl succinate (alpha-TOS), alpha-tocopheryl acetyl
      ether (alpha-TEA) and triphenylphosphonium-tagged vitamin E succinate
      (mitochondrially targeted vitamin E succinate; MitoVES) on energy-related
      mitochondrial functions were determined in mitochondria isolated from AS-30D
      hepatoma and rat liver, bovine heart sub-mitochondrial particles (SMPs), and in
      rodent and human carcinoma cell lines and rat hepatocytes. In isolated
      mitochondria, MitoVES stimulated basal respiration and ATP hydrolysis, but
      inhibited net state 3 (ADP-stimulated) respiration and Ca(2+) uptake, by
      collapsing the membrane potential at low doses (1-10MUM). Uncoupled mitochondrial
      respiration and basal respiration of SMPs were inhibited by the three drugs at
      concentrations at least one order of magnitude higher and with different
      efficacy: MitoVES>alpha-TEA>alpha-TOS. At high doses (>10MUM), the respiratory
      complex II (CII) was the most sensitive MitoVES target. Acting as an uncoupler at
      low doses, this agent stimulated total O(2) uptake, collapsed ?psi(m), inhibited
      oxidative phosphorylation and induced ATP depletion in rodent and human cancer
      cells more potently than in normal rat hepatocytes. These findings revealed that
      in situ tumor mitochondria are preferred targets of the drug, indicating its
      clinical relevance.

PMID- 22627083
TI  - The harmful alga Aureococcus anophagefferens utilizes 19'-butanoyloxyfucoxanthin
      as well as xanthophyll cycle carotenoids in acclimating to higher light
      intensities.
AB  - Aureococcus anophagefferens is a picoplanktonic microalga that is very well
      adapted to growth at low nutrient and low light levels, causing devastating
      blooms ("brown tides") in estuarine waters. To study the factors involved in long
      term acclimation to different light intensities, cells were acclimated for a
      number of generations to growth under low light (20MUmolphotonsm(-2)s(-1)),
      medium light (60 or 90MUmolphotonsm(-2)s(-1)) and high light (200MUmolphotonsm(
      2)s(-1)), and were analyzed for their contents of xanthophyll cycle carotenoids
      (the D pool), fucoxanthin and its derivatives (the F pool), Chls c(2) and c(3),
      and fucoxanthin Chl a/c polypeptides (FCPs). Higher growth light intensities
      resulted in increased steady state levels of both diadinoxanthin and
      diatoxanthin. However, it also resulted in the conversion of a significant
      fraction of fucoxanthin to 19'-butanoyloxyfucoxanthin without a change in the
      total F pool. The increase in 19'-butanoyloxyfucoxanthin was paralleled by a
      decrease in the effective antenna size, determined from the slope of the change
      in F(0) as a function of increasing light intensity. Transfer of acclimated
      cultures to a higher light intensity showed that the conversion of fucoxanthin to
      its derivative was a relatively slow process (time-frame of hours). We suggest
      the replacement of fucoxanthin with the bulkier 19'-butanoyloxyfucoxanthin
      results in a decrease in the light-harvesting efficiency of the FCP antenna and
      is part of the long-term acclimative response to growth at higher light
      intensities.

PMID- 22627084
TI  - Absent left main with anomalous origin of all three coronary arteries from left
      aortic sinus: a previously undescribed combination of coronary anomalies.
AB  - Coronary artery anomalies resulting in all three coronary arteries arising
      separately from single sinus of Valsalva is very rare. We report a patient with
      two coincidental coronary anomalies: absent left main with left anterior
      descending, and left circumflex arteries arising separately from left sinus of
      Valsalva along with anomalous origin of right coronary artery from left sinus of
      Valsalva. Computed tomography angiogram and conventional coronary angiogram
      showed anomalous right coronary artery from left sinus with an interarterial
      course, but with no significant lesions. However, there was significant stenosis
      of left anterior descending and circumflex arteries that was treated with
      angioplasty and stenting. To the best of our knowledge, absent left main with all
      three major coronary arteries arising separately from left aortic sinus has never
      been reported previously.

PMID- 22627085
TI  - Role of donor defects in stabilizing room temperature ferromagnetism in (Mn, Co)
      co-doped ZnO nanoparticles.
AB  - We report the effects of co-doping ZnO with Co and Mn in an n-type environment on
      ferromagnetism (FM). Two sets of samples, Zn(0.95-x)Co(0.04)Mn(x)O (0.000 <= x <=
      0.02) and Zn(0.95-y)Co(y)Mn(0.04)O (0.000 <= y <= 0.02), were synthesized by the
      chemical route with oxygen vacancies introduced via annealing in a forming gas
      (reducing the atmosphere). In addition to the magnetization, the particles were
      characterized by x-ray diffraction, diffuse reflectance spectroscopy and x-ray
      absorption near-edge emission spectroscopy. The Co and Mn ions were determined to
      be in the + 2 state in a tetrahedral symmetry, with no evidence of metallic Co or
      Mn. We find that while a purely Mn-doped sample exhibits weak FM at room
      temperature, the general effect of Mn as a co-dopant with Co, in an n-type
      environment, is to decrease the moment strongly. All of our results can be
      systematically explained within the context of defect mediated FM in these wide
      bandgap semiconductors, where the coincidence of the spin-split-impurity (defect)
      band states and the 3d states leads to the development of a net moment alongside
      the formation of spin polarons.

PMID- 22627086
TI  - Exogenous predictors of national performance measures for emergency department
      crowding.
AB  - STUDY OBJECTIVE: We explore the relationship between exogenous-level predictors
      and performance on 4 emergency department (ED) throughput measures approved by
      the National Quality Forum: median ED length of visit for admitted and discharged
      patients, median waiting time, and rate of left without being seen. We seek to
      find predictors for benchmarking and public reporting. METHODS: This was a study
      of 424 US hospitals that reported data to the National Hospital Ambulatory Care
      Survey in 2008 to 2009. Wald F tests and generalized linear models were used to
      test the relationship between exogenous variables (case mix, age mix, ED volume,
      teaching status, and Metropolitan Statistical Area status) and performance on the
      measures. RESULTS: Median waiting time was 35 minutes (95% confidence interval
      [CI] 26 to 43 minutes), median length of visit for patients treated but not
      admitted was 131 minutes (95% CI 121 to 142 minutes), median length of visit for
      patients admitted was 244 minutes (95% CI 218 to 270 minutes), and rate of left
      without being seen was 1.3% (95% CI 0.9% to 1.8%). Most exogenous variables,
      including ED volume, Metropolitan Statistical Area, teaching hospital status, age
      mix, and case mix, demonstrated significant association with waiting times and
      lengths of visit. Older age and a higher proportion of respiratory complaints
      were associated with differences in rates of left without being seen. CONCLUSION:
      Several exogenous factors outside of a hospital's control are associated with
      National Quality Forum-approved ED performance measures, which will have
      important implications for future benchmarking and public reporting of these
      data.

PMID- 22627087
TI  - An ethical framework for assessments of criminal responsibility: applying Susan
      Wolf's account of sanity to forensic psychiatry.
AB  - Within the context of an ethical theory of responsibility, Susan Wolf has argued
      that people can only be considered fully responsible for their actions when they
      are sane. In this paper I explore the possibility of applying her ethical account
      of sanity and responsibility to forensic assessments of criminal responsibility.
      I argue that after some substantial revisions her account can be helpful in order
      to arrive at an ethics-based conceptual framework for forensic psychiatric
      assessments within the context of an insanity defense.

PMID- 22627088
TI  - [Toxocara canis cerebral vasculitis revealed by iterative strokes].
AB  - INTRODUCTION: Cerebral vasculitis is a rare and severe condition, posing problems
      for diagnosis and treatment. Toxocara canis cerebral vasculitis is exceptionally
      rare, with only 4 cases having been reported. We report an additional case
      revealed by iterative strokes. OBSERVATION: A 49-years-old Laotian man presented
      with right ACA infarction associated with contrast enhancement of cerebrospinal
      fluid, and multiple segmental stenoses in small and medium caliber encephalic
      arteries, in a context of hypereosinophilia and chronic headaches. Laboratory
      tests showed lymphocytic meningitis and T. canis antibody IgE in the blood and
      CSF. The diagnosis of T. canis cerebral vasculitis was retained. During follow
      up, the patient presented again with left pontine hemorrhagic stroke.
      Conventional cerebral angiography confirmed progression of vasculitis despite
      treatment. CONCLUSION: This case-report illustrates the diagnostic and
      therapeutic difficulties associated with vasculitis.

PMID- 22627089
TI  - Comparative effectiveness of mailed reminder letters on mammography screening
      compliance.
AB  - OBJECTIVE: Reminder letters are effective at prompting women to schedule
      mammograms. Less well studied are reminders addressing multiple preventive
      service recommendations. We compared the effectiveness of a mammogram-specific
      reminder sent when a woman was due for a mammogram to a reminder letter
      addressing multiple preventive services and sent on a woman's birthday on
      mammography receipt. METHODS: The study included 48,583 women 52-74 years
      enrolled in Group Health Cooperative, a health plan in Washington State. From
      2005 to 2009, women were mailed 88,605 mammogram-specific or birthday letters. In
      this one group pretest-posttest study, we modeled the odds of obtaining a
      screening mammogram after receiving a letter by reminder type using logistic
      regression, controlling for demographic and healthcare use characteristics and
      stratifying by whether women were overdue or up-to-date with mammography at the
      mailing. RESULTS: Among women up-to-date with screening, birthday letters were
      negatively associated with mammography receipt compared to mammogram-specific
      letters (birthday letters with 1-2 recommendations: OR=0.73; 95% CI:0.68-0.79; 3
      recommendations: OR=0.74; 95% CI:0.69-0.78; 4-8 recommendations: OR=0.62 95%
      CI:0.55-0.68) after. Among overdue women, birthday letters with 4-8
      recommendations were negatively associated with mammography receipt. CONCLUSIONS:
      Transitioning from mammogram-specific reminder letters to multiple preventive
      service birthday letters was associated with decreased mammography receipt.

PMID- 22627090
TI  - Scavenger receptor A (SR-A) is required for LPS-induced TLR4 mediated NF-kappaB
      activation in macrophages.
AB  - Recent evidence suggests that the macrophage scavenger receptor class A (SR-A,
      aka, CD204) plays a role in the induction of innate immune and inflammatory
      responses. We investigated whether SR-A will cooperate with Toll-like receptors
      (TLRs) in response to TLR ligand stimulation. Macrophages (J774/a) were treated
      with Pam2CSK4, (TLR2 ligand), Polyinosinic:polycytidylic acid (Poly I:C) (TLR3
      ligand), and Lipopolysaccharides (LPS) (TLR4 ligand) for 15 min in the presence
      or absence of fucoidan (the SR-A ligand). The levels of phosphorylated
      IkappaBalpha (p-IkappaBalpha) were examined by Western blot. We observed that
      Poly I:C and LPS alone, but not Pam2CSK4 or fucoidan increased the levels of p
      IkappaBalpha. However, LPS-induced increases in p-IkappaBalpha levels were
      further enhanced when presence of the fucoidan. Immunoprecipitation and double
      fluorescent staining showed that LPS stimulation promotes SR-A association with
      TLR4 in the presence of fucoidan. To further confirm our observation, we isolated
      peritoneal macrophages from SR-A deficient (SR-A(-/-)), TLR4(-/-) and wild type
      (WT) mice, respectively. The peritoneal macrophages were treated with LPS for
      15min in the presence and absence of fucoidan. We observed that LPS-stimulated
      TNFalpha and IL-1beta production was further enhanced in the WT macrophages, but
      did not in either TLR4(-/-) or SR-A(-/-) macrophages, when fucoidan was present.
      Similarly, in the presence of fucoidan, LPS-induced IkappaBalpha phosphorylation,
      NF-kappaB binding activity, and association between TLR4 and SR-A were
      significantly enhanced in WT macrophages compared with LPS stimulation alone. The
      data suggests that SR-A is needed for LPS-induced inflammatory responses in
      macrophages.

PMID- 22627091
TI  - The functional benefits of criticality in the cortex.
AB  - Rapidly growing empirical evidence supports the hypothesis that the cortex
      operates near criticality. Although the confirmation of this hypothesis would
      mark a significant advance in fundamental understanding of cortical physiology, a
      natural question arises: What functional benefits are endowed to cortical
      circuits that operate at criticality? In this review, we first describe an
      introductory-level thought experiment to provide the reader with an intuitive
      understanding of criticality. Second, we discuss some practical approaches for
      investigating criticality. Finally, we review quantitative evidence that three
      functional properties of the cortex are optimized at criticality: 1) dynamic
      range, 2) information transmission, and 3) information capacity. We focus on
      recently reported experimental evidence and briefly discuss the theory and
      history of these ideas.

PMID- 22627092
TI  - Prolonged administration of bisphosphonates is well-tolerated and effective for
      skeletal-related events in Chinese breast cancer patients with bone metastasis.
AB  - OBJECTIVE: To evaluate the long-term tolerability and activity of prolonged
      administration of bisphosphonates (BPs) in breast cancer (BrCa) patients with
      bone metastasis (BM). METHODS: We retrospectively analyzed safety data and
      activity of BPs in BrCa patients with BM who had received intravenous BPs for >24
      months. Renal toxicity, osteonecrosis of the jaw (ONJ), and hypocalcemia were
      assessed. In addition, levels of creatinine (Cr) and calcium (Ca) in pre- and
      post-treatment sera were examined. The following parameters were also analyzed:
      the proportion of patients with at least one skeletal-related event (SRE), the
      distribution of each type of SRE, and the skeletal morbidity rate (SMR). RESULTS:
      181 patients from January 1, 2005 to May 31, 2009 were enrolled in the study. The
      median BP administration period was 36 (range: 25-133) months. Grades 1-2 and 3
      renal toxicity occurred in 3.9% and 0.7% of patients, respectively. Only one
      patient was diagnosed with ONJ, the incidence rate of which was 0.6%.
      Hypocalcemia occurred in 29 patients (16.0%), most frequently after two years of
      BP therapy. Neither serum Cr levels nor the creatinine clearance rate were
      significantly increased by treatment. Furthermore, 50 patients (27.6%)
      experienced a new SRE between zero and 24 months after BP therapy. However, no
      notable increase in incidence rate of SREs was observed after the two years of BP
      treatment. Overall, 63 patients (34.8%) experienced at least one new SRE after
      initiation of BPs (p = 0.173). No significant difference was found among the
      different BP subgroups of pamidronate, ibandronate, and zoledronate. Radiation to
      bone was the most common cause of SREs (68.4%, 67/98). SMR was 0.10 events per
      year for 0-5 years after BP treatment. CONCLUSIONS: This was the largest
      retrospective study of extended use of BPs in BrCa patients with BM. Intravenous
      administration of BPs was well-tolerated and remained active throughout the
      prolonged period of administration. The occurrence of SREs was similar among the
      pamidronate, ibandronate, and zoledronate subgroups after two years of BP
      treatment.

PMID- 22627093
TI  - Alzheimer culprits: cellular crossroads and interplay.
AB  - Alzheimer's disease (AD) is the primary cause of dementia in the elderly and one
      of the major health problems worldwide. Since its first description by Alois
      Alzheimer in 1907, noticeable but insufficient scientific comprehension of this
      complex pathology has been achieved. All the research that has been pursued takes
      origin from the identification of the pathological hallmarks in the forms of
      amyloid-beta (Abeta) deposits (plaques), and aggregated hyperphosphorylated tau
      protein filaments (named neurofibrillary tangles). Since this discovery, many
      hypotheses have been proposed to explain the origin of the pathology. The
      "amyloid cascade hypothesis" is the most accredited theory. The mechanism
      suggested to be one of the initial causes of AD is an imbalance between the
      production and the clearance of Abeta peptides. Therefore, Amyloid Precursor
      Protein (APP) synthesis, trafficking and metabolism producing either the toxic
      Abeta peptide via the amyloidogenic pathway or the sAPPalpha fragment via the non
      amyloidogenic pathway have become appealing subjects of study. Being able to
      reduce the formation of the toxic Abeta peptides is obviously an immediate
      approach in the trial to prevent AD. The following review summarizes the most
      relevant discoveries in the field of the last decades.

PMID- 22627094
TI  - Regulation of SLC26A3 activity by NHERF4 PDZ-mediated interaction.
AB  - SLC26A3 functions as a chloride/bicarbonate anion exchanger expressed in the
      secretory epithelial cells in the intestine, pancreas, and salivary glands.
      SLC26A3 has a C-terminal class I PDZ binding motif that assembles regulatory
      factors or other transporters by anchoring to various PDZ scaffold proteins.
      NHERF4 is an epithelial-enriched PDZ domain scaffold protein that has attracted
      attention because of its enriched tissue expression in the intestine and kidney.
      In this study, we identified SLC26A3 as a novel binding transporter of NHERF4. We
      investigated the functional role of NHERF4 in the regulation of SLC26A3 by using
      integrated biochemical and physiological approaches. A direct protein-protein
      interaction was identified between the PDZ-binding motif of SLC26A3 and the third
      PDZ domain of NHERF4. Interaction with NHERF4 decreased the level of SLC26A3
      expression on the plasma membrane, which led to reduced SLC26A3 anion exchange
      activity. Notably, interaction with NHERF4 induced rapid internalisation of
      SLC26A3 from the plasma membrane. The SLC26A3-NHERF4 interaction was modulated by
      phosphorylation; serine 329 of NHERF4-PDZ3 played a critical role in modulating
      binding selectivity. Our findings suggest that NHERF4 is a novel modulator of
      luminal fluidity in the intestine by adjusting SLC26A3 expression and activity
      through a phosphorylation-dependent mechanism.

PMID- 22627096
TI  - The multiple faces of host defence peptides and proteins.

PMID- 22627095
TI  - The translational role of diffusion tensor image analysis in animal models of
      developmental pathologies.
AB  - Diffusion tensor magnetic resonance imaging (DTI) has proven itself a powerful
      technique for clinical investigation of the neurobiological targets and
      mechanisms underlying developmental pathologies. The success of DTI in clinical
      studies has demonstrated its great potential for understanding translational
      animal models of clinical disorders, and preclinical animal researchers are
      beginning to embrace this new technology to study developmental pathologies. In
      animal models, genetics can be effectively controlled, drugs consistently
      administered, subject compliance ensured, and image acquisition times
      dramatically increased to reduce between-subject variability and improve image
      quality. When pairing these strengths with the many positive attributes of DTI,
      such as the ability to investigate microstructural brain organization and
      connectivity, it becomes possible to delve deeper into the study of both normal
      and abnormal development. The purpose of this review is to provide new
      preclinical investigators with an introductory source of information about the
      analysis of data resulting from small animal DTI studies to facilitate the
      translation of these studies to clinical data. In addition to an in-depth review
      of translational analysis techniques, we present a number of relevant clinical
      and animal studies using DTI to investigate developmental insults in order to
      further illustrate techniques and to highlight where small animal DTI could
      potentially provide a wealth of translational data to inform clinical
      researchers.

PMID- 22627097
TI  - Positive clinical risk factors predict a high rate of methicillin-resistant
      Staphylococcus aureus colonization in emergency department patients.
AB  - BACKGROUND: This study was undertaken to determine the rate of methicillin
      resistant Staphylococcus aureus (MRSA) colonization predicted by clinical risk
      factors compared with determination by nasal swab culture and polymerase chain
      reaction in emergency department patients. METHODS: From November 2009 to March
      2011, patients seen in the emergency department were studied prospectively. The
      risk of MRSA colonization was determined by clinical risk factors, and both
      surveillance cultures and a polymerase chain reaction assay were performed in
      each patient. RESULTS: A total of 277 patients was enrolled, and 31.4% (87/277)
      of patients had a positive surveillance culture or a MRSA polymerase chain
      reaction assay. The rate of colonization in patients with high-risk factors
      included the following: past history of colonization/infections, 60.0%; history
      of previous antibiotic use, 47.2%; more than 30 days hospitalization in the past
      3 months, 43.9%; more than 10 days hospitalization in the past 3 months, 41.7%;
      and a history of hospitalization because of acute illness, 40.0%. CONCLUSION: The
      prevalence rate of colonization in patients with a high risk of MRSA colonization
      exceeded 30%. Active surveillance cultures should be considered in patients at
      high risk for MRSA colonization.

PMID- 22627098
TI  - Rituximab-induced hepatitis C virus reactivation in rheumatoid arthritis.
AB  - The B-cell depletion agent rituximab (RTX) is used in lymphoma and rheumatoid
      arthritis (RA), and there have been several case reports of an RTX-induced
      reactivation of hepatitis C virus in patients with lymphoma. However, there have
      been no papers detailing hepatitis C virus reactivation after RTX therapy in a
      patient with RA. Here we report a case of RTX-induced hepatitis C virus
      reactivation in a patient with RA. Physicians should be aware that a close follow
      up of liver function and viral load is mandatory after RTX therapy in patients
      with RA and concomitant hepatitis C.

PMID- 22627099
TI  - Ab initio calculations of the forbidden Bragg reflections energy spectra in
      wurtzites versus temperature.
AB  - Thermal-motion induced (TMI) scattering is caused by the influence of atomic
      displacements on electronic states in crystals and strongly depends on
      temperature. It corresponds to dipole-dipole resonant x-ray scattering, but is
      usually accompanied by dipole-quadrupole scattering. The phenomenological theory
      supposes the dipole-quadrupole term to be temperature independent (TI). As a
      result, the transformation of the energy spectra with temperature observed
      experimentally in ZnO and GaN corresponds to the interference between the TMI and
      TI terms. In the present paper the direct confirmation of this theoretical
      prediction is given. Ab initio molecular dynamics was used to simulate the sets
      of atomic sites at various temperatures followed by quantum mechanical
      calculation of resonant Bragg reflection energy spectra. The results of
      simulation are in excellent coincidence with experimental energy spectra of
      forbidden reflections and confirm the earlier phenomenological conjecture about
      the interference between the TI dipole-quadrupole and TMI dipole-dipole
      contributions to the resonant atomic factor.

PMID- 22627101
TI  - Immunogenicity and safety of yellow fever vaccine among 115 HIV-infected patients
      after a preventive immunisation campaign in Mali.
AB  - The immune response to yellow fever (YF) vaccine and its safety among HIV
      infected individuals living in YF endemic areas is not well understood. Following
      a national YF preventive immunisation campaign in Mali in April 2008, we assessed
      the immunogenicity and safety of 17D yellow fever vaccine (17DV) among HIV
      infected patients in two HIV treatment centres in Bamako, Mali, by testing for
      neutralising antibodies and identifying serious adverse events following
      immunisation (AEFI). A YF neutralisation titre (NT) of 1:>=20 was considered to
      be adequate and protective. A serious AEFI included hospitalisation, any life
      threatening condition, or death, occurring within 30 days following 17DV
      administration. Of 115 HIV-infected patients who reported having received 17DV,
      110 (96%) were on combination antiretroviral therapy and 83 patients were tested
      for neutralising antibodies. Around the time of vaccination, median CD4 cell
      count was 389 cells/mm(3) (IQR 227-511cells/mm(3)); HIV-RNA was undetectable in
      24 of 46 patients tested. Seventy-six (92%) of 83 participants had adequate
      immune titres 9 months after the immunisation campaign. Previous vaccination or
      flavivirus exposure could contribute to this finding. No serious AEFI was found
      in the 115 participants. In this small series, YF vaccine appeared to be
      immunogenic with a favourable safety profile in HIV-infected patients on
      antiretroviral therapy. Higher CD4 cell counts and suppressed HIV-RNA were
      associated with the presence of an adequate immune titre and higher NTs.

PMID- 22627100
TI  - Chiropractic care of children from birth to adolescence and classification of
      reported conditions: an internet cross-sectional survey of 956 European
      chiropractors.
AB  - OBJECTIVE: Few studies have addressed the practice of chiropractic care of
      children in Europe. No systematic classification of conditions currently exists
      in chiropractic pediatrics. The objective of this study was to investigate
      characteristics of clinical chiropractic practice, including the age of pediatric
      patients, the number of reports of negative side effects (NSEs), the opinions of
      doctors of chiropractic on treatment options by patient age groups, the
      conditions seen and the number of treatment sessions delivered by conditions and
      by patient age. METHODS: An Internet cross-sectional survey was conducted in 20
      European countries with 4109 doctors of chiropractic invited to reply. The 19
      national associations belonging to the European Chiropractic Union and the Danish
      Chiropractic Association were asked to participate. Respondents were asked to
      self-report characteristics of their practices. RESULTS: Of the 956 (23.3%)
      participating chiropractors, 921 reported 19821 pediatric patients per month.
      Children represented 8.1% of chiropractors' total patient load over the last
      year. A total of 557 (534 mild, 23 moderate, and 0 severe) negative (adverse)
      side effects were reported for an estimated incidence of 0.23%. On the given
      treatment statements, chiropractors reported varying agreement and disagreement
      rates based on patient age. The 8309 answers on conditions were grouped into
      skeletal (57.0%), neurologic (23.7%), gastrointestinal (12.4%), infection (3.5%),
      genitourinary (1.5%), immune (1.4%), and miscellaneous conditions (0.5%). The
      number of treatment sessions delivered varied according to the condition and the
      patient age. CONCLUSION: This study showed that European chiropractors are active
      in the care of pediatric patients. Reported conditions were mainly skeletal and
      neurologic complaints. In this survey, no severe NSEs were reported, and mild
      NSEs were infrequent.

PMID- 22627102
TI  - The role of prothrombin time (PT) in evaluating green pit viper (Cryptelytrops
      sp) bitten patients.
AB  - Viper bites cause consumptive coagulopathy resulting in hypofibrinogenaemia.
      Whole-blood clotting time is a standard test used to assess bleeding risk.
      Prothrombin time (PT) and activated partial thromboplastin time (APTT) are better
      standardised assays that are widely available, but their diagnostic accuracy in
      viper bites remains unknown. Adult patients presumed bitten by green pit vipers
      (Cryptelytops sp.) were enrolled. Conventional venous clotting time (VCT), 20min
      whole-blood clotting time (20WBCT), PT with international normalized ratio (INR)
      and APTT were determined. A fibrinogen level below 1.0g/litre was used as the
      gold standard. There were 97 patients. The average age was 46.1 years and 49.5%
      were men. VCT >30min, INR >1.2 and fibrinogen level <1.0g/litre were found in
      9.3, 10.3 and 7.2%, respectively. The sensitivities of VCT >30min, 20WBCT (N=55),
      INR and APTT were 57.0%, 85.7%, 85.7% and 57.1%, respectively. The respective
      specificities were 94.4%, 95.8%, 95.6% and 72.4%. Three hypofibrinogenaemic
      patients who did not receive antivenom because of VCT <30min had persistently
      normal VCT and went home without clinical bleeding. In conclusion, PT with INR
      can be an alternative test for evaluation of coagulopathy in green pit viper
      bitten patients with potentially improved inter-laboratory standardisation.

PMID- 22627103
TI  - Rectal cancer--the times they are a-changing.

PMID- 22627105
TI  - Nifedipine inhibits hypoxia induced transvascular leakage through down regulation
      of NFkB.
AB  - We have studied the prophylactic administration of nifedipine and its molecular
      mechanism involved in reducing the transvascular leakage and inflammation in rats
      under hypoxia. Rats exposed to an altitude of 7620m for 6h resulted into
      significant increase in transvascular leakage, oxidative stress with increased
      NFkB expression in lungs followed by significant increase in pro inflammatory
      cytokines (IL-1, TNF-alpha) with up regulation of cell adhesion molecules (ICAM
      I, VCAM-I, E-selectin, and P-selectin) in the lungs over control. Prophylactic
      administration of nifedipine significantly reduced the transvascular leakage,
      oxidative stress, inhibited the up regulation of NFkB in lungs of rats compared
      to control. In addition, nifedipine significantly suppressed the levels of
      proinflammatory cytokines and cell adhesion molecules and stabilized the HIF1
      alpha accumulation in the lungs of rats compared to control. These results
      indicate that, nifedipine has an inhibitory effect on initial leaking and showed
      reduction in progression of inflammation through down regulation of NFkB activity
      in lungs of rats under hypoxia.

PMID- 22627106
TI  - Isolation, identification and characterization of a novel antioxidant protein
      from the nematocyst of the jellyfish Stomolophus meleagris.
AB  - Reactive oxygen species (ROS) can damage the lipids, proteins and DNA when
      produced excessively in cells. Here, we describe the isolation and identification
      of a novel antioxidant protein named SmP90 from the nematocyst of jellyfish
      Stomolophus meleagris by 50% ammonium sulfate precipitation and gel filtration
      chromatography, superdex75. HPLC and SDS-PAGE analysis revealed >95% purity of
      SmP90 with apparent molecular weight of 90 kDa, approximately. The identification
      of SmP90 was confirmed by both N-terminal amino acids sequencing, with the
      sequences of NLDTPYCFYSGDYGG, and peptide mass fingerprint (PMF) analysis by
      MALDI-TOF-MS. However, no known protein had been completely matched in the
      database, which indicated that SmP90 might be a novel protein. The antioxidant
      assay result showed that it had strong superoxide anion radical-scavenging
      activity with the half-scavenging concentration (EC(50)) of about 16 MUg/mL.
      Therefore, the present study is the first time to demonstrate a high efficient
      method of isolating a novel antioxidant protein from the nematocyst of jellyfish
      S. meleagris.

PMID- 22627107
TI  - Changes in urinary and sexual function 6 months after cystocele repair with a
      polypropylene mesh.
AB  - INTRODUCTION: We used quantitative parameters obtained during the voiding phase,
      urinary symptoms and sexual functioning to investigate the symptomatic and
      functional changes after cystocele repair with a polypropylene mesh. PATIENTS AND
      METHODS: The maximum urinary flow rate (Q(max)), residual urine (RU) volume and
      two symptom questionnaires, the Urinary Distress Inventory (UDI-6) and the Female
      Sexual Function Index (FSFI), were used to retrospectively evaluate 39
      consecutive cystocele patients before and 6 months after surgery. RESULTS:
      Q(max), RU and FSFI were not significantly different (p = 0.366, 0.286 and 0.100,
      respectively) pre- and postoperatively, but the UDI-6 score had significantly
      improved (p < 0.001) 6 months after the cystocele repair. A concomitant sling
      procedure was significantly correlated with changes in the UDI-6 score (p <
      0.001); the patients without stress urinary incontinence (SUI) who underwent
      cystocele repair only showed no symptomatic improvements in the UDI-6 score (p =
      0.560). CONCLUSIONS: Correction of SUI resulted in urinary symptom improvement in
      cystocele patients. Cystocele repair with or without sling placement did not
      change Q(max), RU or sexual functioning at the 6-month follow-up.

PMID- 22627108
TI  - Functions of plasmalogen lipids in health and disease.
AB  - Plasmalogens are a unique class of membrane glycerophospholipids containing a
      fatty alcohol with a vinyl-ether bond at the sn-1 position, and enriched in
      polyunsaturated fatty acids at the sn-2 position of the glycerol backbone. These
      two features provide novel properties to these compounds. Although plasmalogens
      represent up to 20% of the total phospholipid mass in humans their physiological
      roles have been challenging to identify, and are likely to be particular to
      different tissues, metabolic processes and developmental stages. Their
      biosynthesis starts in peroxisomes, and defects at these steps cause the
      malformation syndrome, Rhizomelic Chondrodysplasia Punctata (RCDP). The RCDP
      phenotype predicts developmental roles for plasmalogens in bone, brain, lens,
      lung, kidney and heart. Recent studies have revealed secondary plasmalogen
      deficiencies associated with more common disorders and allow us to tease out
      additional pathways dependent on plasmalogen functions. In this review, we
      present current knowledge of plasmalogen biology in health and disease.

PMID- 22627109
TI  - Transfection efficiency boost of cholesterol-containing lipoplexes.
AB  - Most lipid formulations require cholesterol for successful transfection, but the
      precise reason remains to be more clearly understood. Here, we have studied the
      effect of cholesterol on the transfection efficiency (TE) of lipoplexes in vitro.
      Addition of cholesterol to highly effective DC-Chol-DOPE/DNA lipoplexes increases
      TE, with 40 mol% cholesterol yielding about 10-fold improvement. The transfection
      mechanisms of cholesterol-containing lipoplexes have been investigated by
      combining dynamic light scattering, synchrotron small angle X-ray scattering,
      laser scanning confocal microscopy and transfection efficiency measurements. Our
      results revealed that cholesterol-containing lipoplexes enter the cells partially
      by membrane fusion and this mechanism accounts for efficient endosomal escape. We
      also found evidence that formulations with high cholesterol content are not
      specifically targeted to metabolic degradation. These studies will contribute to
      rationally design novel delivery systems with superior transfection efficiency.

PMID- 22627110
TI  - Difference in lipid packing sensitivity of exchangeable apolipoproteins apoA-I
      and apoA-II: an important determinant for their distinctive role in lipid
      metabolism.
AB  - Exchangeable apolipoproteins A-I and A-II play distinct roles in reverse
      cholesterol transport. ApoA-I interacts with phospholipids and cholesterol of the
      cell membrane to make high density lipoprotein particles whereas apolipoprotein A
      II interacts with high density lipoprotein particles to release apolipoprotein A
      I. The two proteins show a high activity at the aqueous solution/lipid interface
      and are characterized by a high content of amphipathic alpha-helices built upon
      repetition of the same structural motif. We set out to investigate to what extent
      the number of alpha-helix repeats of this structural motif modulates the affinity
      of the protein for lipids and the sensitivity to lipid packing. To this aim we
      have compared the insertion of apolipoproteins A-I and A-II in phospholipid
      monolayers formed on a Langmuir trough in conditions where lipid packing, surface
      pressure and charge were controlled. We also used atomic force microscopy to
      obtain high resolution topographic images of the surface at a resolution of
      several nanometers and performed statistical image analysis to calculate the
      spatial distribution and geometrical shape of apolipoproteins A-I and A-II
      clusters. Our data indicate that apolipoprotein A-I is sensitive to packing of
      zwitterionic lipids but insensitive to the packing of negatively charged lipids.
      Interestingly, apolipoprotein A-II proved to be insensitive to the packing of
      zwitterionic lipids. The different sensitivity to lipid packing provides clues as
      to why apolipoprotein A-II barely forms nascent high density lipoprotein
      particles while apolipoprotein A-I promotes their formation. We conclude that the
      different interfacial behaviors of apolipoprotein A-I and apolipoprotein A-II in
      lipidic monolayers are important determinants of their distinctive roles in lipid
      metabolism.

PMID- 22627112
TI  - [Progressive ossifying fibrodysplasia, the stone man syndrome].

PMID- 22627111
TI  - Endothelin-1 stimulates small artery VCAM-1 expression through p38MAPK-dependent
      neutral sphingomyelinase.
AB  - Endothelin-1 (ET-1) stimulates vascular cell adhesion molecule (VCAM-1)
      expression, a process associated with arterial remodelling. However, the pathways
      activated by ET-1 that lead to VCAM-1 expression are not fully understood. It is
      reported that sphingomyelinases are necessary for VCAM-1 expression in response
      to cytokines. Our aim was to investigate the role of sphingomyelinases in ET-1
      induced VCAM-1 expression. Acid and neutral sphingomyelinase activities were
      measured in extracts from rat mesenteric small arteries (RMSA). ET-1 (1-100
      nmol/l) stimulated neutral but not acid sphingomyelinase. The activation was
      rapid, peaking within 5 min and transient, returning towards baseline by 10 min
      and inhibited by BQ-788, GW4869 and SB203580, which are inhibitors of ET(B)
      receptor, neutral sphingomyelinase and p38MAPK, respectively. Both GW4869 and
      SB203580 are reported to inhibit activation of neutral sphingomyelinase 2
      implicating it in the response to ET-1. Accordingly we investigated the
      expression of this isoform and found it was present in RMSA, predominantly in
      endothelial cells. Treatment of RMSA with ET-1 (1-100 nmol/l) for 16 h increased
      VCAM-1 expression, which was inhibited by GW4869 and SB203580. These results
      indicate that ET-1 stimulates arterial VCAM-1 expression through p38MAPK
      dependent activation of neutral sphingomyelinases. This suggests a role for
      sphingolipids in ET-1-induced vascular inflammation in cardiovascular disease.

PMID- 22627113
TI  - Climacteric lowers plasma levels of platelet-derived microparticles: a pilot
      study in pre- versus postmenopausal women.
AB  - BACKGROUND: Climacteric increases the risk of thrombotic events by alteration of
      plasmatic coagulation. Up to now, less is known about changes in platelet- (PMP)
      and endothelial cell-derived microparticles (EMP). METHODS: In this prospective
      study, plasma levels of microparticles (MP) were compared in 21 premenopausal and
      19 postmenopausal women. RESULTS: No altered numbers of total MP or EMP were
      measured within the study groups. However, the plasma values of CD61-exposing MP
      from platelets/megakaryocytes were higher in premenopausal women (5,364 *
      10(6)/l, range 4,384-17,167) as compared to postmenopausal women (3,808 *
      10(6)/l, range 2,009-8,850; p = 0.020). This differentiation was also significant
      for the subgroup of premenopausal women without hormonal contraceptives (5,364 *
      10(6)/l, range 4,223-15,916; p = 0.047; n = 15). Furthermore, in premenopausal
      women, higher plasma levels of PMP exposing CD62P were also present as compared
      to postmenopausal women (288 * 10(6)/l, range 139-462, vs. 121 * 10(6)/l, range
      74-284; p = 0.024). This difference was also true for CD63+ PMP levels (281 *
      10(6)/l, range 182-551, vs. 137 * 10(6)/l, range 64-432; p = 0.015). CONCLUSION:
      Climacteric lowers the level of PMP but has no impact on the number of EMP in
      women. These data suggest that PMP and EMP do not play a significant role in
      enhancing the risk of thrombotic events in healthy, postmenopausal women.

PMID- 22627114
TI  - Comparison of coagulation performance and floc properties using a novel zirconium
      coagulant against traditional ferric and alum coagulants.
AB  - Coagulation in drinking water treatment has relied upon iron (Fe) and aluminium
      (Al) salts throughout the last century to provide the bulk removal of
      contaminants from source waters containing natural organic matter (NOM). However,
      there is now a need for improved treatment of these waters as their quality
      deteriorates and water quality standards become more difficult to achieve.
      Alternative coagulant chemicals offer a simple and inexpensive way of doing this.
      In this work a novel zirconium (Zr) coagulant was compared against traditional Fe
      and Al coagulants. The Zr coagulant was able to provide between 46 and 150% lower
      dissolved organic carbon (DOC) residual in comparison to the best traditional
      coagulant (Fe). In addition floc properties were significantly improved with
      larger and stronger flocs forming when the Zr coagulant was used with the median
      floc sizes being 930 MUm for Zr; 710 MUm for Fe and 450 MUm for Al. In pilot
      scale experiments, a similar improved NOM and particle removal was observed. The
      results show that when optimised for combined DOC removal and low residual
      turbidity, the Zr coagulant out-performed the other coagulants tested at both
      bench and pilot scale.

PMID- 22627115
TI  - Effect of magnetic field on Mott's variable-range hopping parameters in multiwall
      carbon nanotube mat.
AB  - We report the temperature and magnetic field dependence of the conductivity of
      multiwall carbon nanotube mat in the temperature range 1.4-150 K and in magnetic
      fields up to 10 T. It is observed that charge transport in this system is
      governed by Mott's variable-range hopping of three-dimensional type in the higher
      temperature range and two-dimensional type in the lower temperature range. Mott's
      various parameters, such as localization length, hopping length, hopping energy
      and density of states at the Fermi level are deduced from the variable-range
      hopping fit. The resistance of the sample decreases with the magnetic field
      applied in the direction of tube axis of the nanotubes. The magnetic field gives
      rise to delocalization of states with the well-known consequence of a decrease in
      Mott's T0 parameter in variable-range hopping. The application of magnetic field
      lowers the crossover temperature at which three-dimensional variable-range
      hopping turns to two-dimensional variable-range hopping. The conductivity on the
      lower temperature side is governed by the weak localization giving rise to
      positive magnetoconductance. Finally, a magnetic field-temperature diagram is
      proposed showing different regions for different kinds of transport mechanism.

PMID- 22627116
TI  - Insecticide and acaricide molecules and/or combinations to prevent pet
      infestation by ectoparasites.
AB  - External antiparasitic drugs used in cats and dogs have evolved in terms of
      active ingredients but also regarding formulations. Old chemical groups have been
      supplanted by phenylpyrazoles, neonicotinoids, oxadiazines, spinosyns or others
      which are entering the veterinary market. In addition to insecticides-acaricides,
      insect and mite growth inhibitors (IGRs) have emerged. These IGRs are used in
      animals or in the environment, either alone or in combination with insecticides
      acaricides. The notion of antiparasitic treatment has evolved to the concept of
      prevention of ectoparasite infestation but also of transmitted diseases through
      the introduction of formulations providing long-lasting activity. At the same
      time, ease-of-use has been improved with the development of spot-on formulations.
      Progress has also been achieved through the development of antiparasitic drugs
      providing control of both external and internal parasites.

PMID- 22627117
TI  - Normative nasalance data in Ugandan english-speaking children.
AB  - AIMS: The aim of this study was to obtain normative nasalance values for
      typically developing Ugandan English-speaking children as a reference point for
      clinical practice and further research. METHODS: Sixty-nine typically developing
      Ugandan children (35 males and 34 females, 2.7-13.5 years of age) participated in
      the study. Nasalance scores were obtained with the Nasometer while children
      repeated 4 sustained sounds, 14 repeated syllables, 15 sentences (12 oral, 3
      nasal) and 2 texts ('Rainbow Passage' and 'Zoo Passage'). Data were analyzed for
      gender and age dependence. RESULTS: No significant effects of age or gender on
      nasalance values were obtained; hence, normative values for the overall group
      were reported. The average nasalance scores for Ugandan English-speaking children
      were 17 and 64% for the oral and nasal sentences and 33 and 14% for the oronasal
      and oral text, respectively. CONCLUSION: The normative values are important as a
      reference point to assess the impact of several surgical procedures and several
      surgical timing strategies on speech in Uganda.

PMID- 22627118
TI  - Shifting trends in bacterial keratitis in Toronto: an 11-year review.
AB  - OBJECTIVE: To review the distribution, current trends, and resistance patterns of
      bacterial keratitis isolates in Toronto over the last 11 years. DESIGN:
      Retrospective, observational, case series. PARTICIPANTS: Microbiology records of
      suspected bacterial keratitis cases that underwent a diagnostic corneal scraping
      and cultures from January 1, 2000, through December 31, 2010, were reviewed.
      METHODS: Culture results and antibiotic sensitivity profiles were reviewed and
      analyzed. MAIN OUTCOME MEASURES: Distribution of the main isolated pathogens as
      well as in vitro laboratory minimum inhibitory concentration testing results to
      identify resistance patterns. RESULTS: A total of 1701 consecutive corneal
      scrapings were taken during the 11 years of the study. A pathogen was recovered
      in 977 samples (57.4%), with bacterial keratitis accounting for 897 of the
      positive cultures (91.8%). The total number of Gram-positive and Gram-negative
      isolates was 684 and 213, respectively. We identified a decreasing trend in Gram
      positive isolates (P = 0.016). The most common isolate overall was coagulase
      negative Staphylococcus (CNS) and the most common Gram-negative bacteria isolated
      was Pseudomonas aeruginosa. Methicillin-resistant Staphylococcus aureus (MRSA)
      was present in 1.3% of the S aureus isolates, whereas methicillin-resistant CNS
      (MRCNS) was present in 43.1% of the CNS isolates. There was a trend toward
      increasing laboratory resistance to methicillin from 28% during the first 4 years
      of the study to 38.8% for the last 3 years (P = 0.133). When analyzing the
      sensitivities of MRSA and MRCNS isolates to other antibiotics, there was
      resistance to cefazolin and sensitivity to vancomycin in all isolates, whereas
      resistance to other antibiotics was variable. CONCLUSIONS: There was a
      significant decrease in the percentage of Gram-positive microorganisms over time.
      The sensitivity of Gram-negative isolates to tested antimicrobials was >97%
      response for all the reported antibiotics; this was not the case for Gram
      positive isolates, in which resistance to the antibiotics was more common.
      Methicillin-resistant organisms accounted for 29.1% of all Gram-positive cultures
      in our series, suggesting that the empiric use of vancomycin in the setting of
      severe suspected bacterial keratitis may be justified.

PMID- 22627119
TI  - Longer axial length is protective of diabetic retinopathy and macular edema.
AB  - PURPOSE: To assess the association of ocular biometric parameters and refractive
      error with diabetic retinopathy (DR) and diabetic macular edema (DME) in persons
      with diabetes. DESIGN: Cross-sectional, clinic-based study. PARTICIPANTS:
      Patients with diabetes aged 18 years or more from the Royal Victorian Eye and Ear
      Hospital, Victoria, Australia. METHODS: Spherical equivalent (SE) refraction was
      assessed using objective autorefraction. Axial length (AL), corneal curvature
      (CC), and anterior chamber depth (ACD) were measured using the IOLMaster (Carl
      Zeiss Meditech AG, Jena, Germany). Diabetic retinopathy was graded from 2-field
      retinal photographs using the modified Airlie House classification system.
      Diabetic macular edema was defined as absent or present from fundus photographs
      and confirmed by optical coherence tomography (Stratus, Carl Zeiss Meditech AG).
      MAIN OUTCOME MEASURES: Severity of DR was grouped as no DR, mild DR (Early
      Treatment of Diabetic Retinopathy Study [ETDRS] = 20), moderate DR (ETDRS = 31
      43), and severe DR (ETDRS >43). Diabetic macular edema severity was classified as
      mild, moderate, or severe. RESULTS: A total of 208 of 630 eyes (33.0%) had DR. In
      multivariate models, eyes with longer AL were less likely to have mild (odds
      ratio [OR], 0.58; 95% confidence interval [CI], 0.41-0.83; P = 0.006 per mm
      increase), moderate (OR, 0.73; 95% CI, 0.60-0.88; P = 0.002), and severe DR (OR,
      0.67; 95% CI, 0.53-0.85; P=0.01), and had a lesser risk of mild (OR, 0.70; 95%
      CI, 0.56-0.86; P < 0.001) and moderate DME (OR, 0.72; 95% CI, 0.56-0.93; P=0.002)
      but not severe DME. No association was found for SE, ACD, and CC with DR.
      CONCLUSIONS: In persons with diabetes, eyes with longer ALs are less likely to
      have DR and DME.

PMID- 22627120
TI  - Vitamin D3 deficiency increases sinus mucosa dendritic cells in pediatric chronic
      rhinosinusitis with nasal polyps.
AB  - OBJECTIVE: Dendritic cells are professional antigen presenting cells, capable of
      initiating Th1 or Th2 responses, and have been implicated in the pathogenesis of
      a number of diseases, including sinusitis. Vitamin D(3) is a steroid hormone that
      acts on dendritic cells in a manner similar to corticosteroids. Investigators
      examined whether children with allergic fungal rhinosinusitis (AFRS) or chronic
      rhinosinusitis with nasal polyposis (CRSwNP) were vitamin D(3) deficient and the
      relationship of vitamin D(3) deficiency to dendritic cell infiltrate in the sinus
      mucosa. SETTING: Tertiary care university hospital. STUDY DESIGN: Retrospective,
      controlled study using samples collected from pediatric patients seen from August
      2009 to July 2011. SUBJECTS AND METHODS: Plasma levels of 25-hydroxy vitamin D(3)
      were measured by enzyme-linked immunosorbent assay in children (<=18 years old)
      with AFRS, CRSwNP, or CRS without nasal polyposis (CRSsNP) and in controls
      undergoing surgery for adenotonsillar hypertrophy. Vitamin D(3) levels were
      confirmed using clinical diagnostic methods for those with CRSwNP or AFRS. Tissue
      samples were immunohistochemically stained for the dendritic cell marker CD209
      and the costimulatory molecules CD80 and CD86. RESULTS: There was no difference
      in mean vitamin D(3) levels between control and CRSsNP, whereas mean CRSwNP and
      AFRS levels were both well below the minimum recommended level of 30 ng/mL and
      significantly lower than control and CRSsNP levels. CD209(+) dendritic cells
      inversely correlated with vitamin D(3) but not costimulatory molecule expression.
      CONCLUSIONS: These studies identify that children with CRSwNP or AFRS are vitamin
      D(3) deficient, which may be linked to increased dendritic cell infiltrate. These
      results suggest a role for vitamin D(3) as a key player in the immunopathology of
      pediatric CRSwNP.

PMID- 22627121
TI  - Efficacy of fibrin sealant for drainage reduction in total thyroidectomy with
      bilateral central neck dissection.
AB  - OBJECTIVE: To investigate the efficacy of fibrin sealant (FS) for reducing
      postoperative drainage in patients who underwent total thyroidectomy (TT) with
      bilateral central neck dissection (CND) for papillary thyroid cancer. STUDY
      DESIGN: Prospective randomized trial. SETTING: Tertiary care institution.
      SUBJECTS AND METHODS: Seventy-eight patients with papillary thyroid cancer were
      enrolled and randomized to either the FS application group (FS+, 38 patients) or
      no FS application group (FS-, 40 patients). In both groups, postoperative
      drainage amounts were measured by a negative suction system until the criterion
      of drain removal was met. Drainage amounts as well as the time to drain removal,
      postoperative complications, and chemical profile assay of drain fluids between
      the 2 groups were performed. RESULTS: Drainage amounts at the initial 24 hours as
      well as total amounts of the FS+ group tended to be lower than those of the FS-
      group; however, they were not statistically different (at initial 24 hours, 64.3
      +/- 17.5 mL vs 73.0 +/- 18.0 mL, P = .06; total amounts, 93.5 +/- 30.7 mL vs
      105.7 +/- 31.2 mL, P = .05). The FS application did not shorten the time to drain
      removal even when different criteria for drain removal were applied (criteria of
      <20 mL/d or <30 mL/d). When chemistry profiles of collected drain fluids were
      analyzed in patient subgroups, the level of triglycerides in the FS+ group was
      significantly lower than in the FS- group. CONCLUSION: Fibrin sealant has no
      additional advantage in terms of drainage reduction and early discharge despite
      the additional medical cost.

PMID- 22627122
TI  - The relationship of trait to state motivation: the role of self-competency
      beliefs.
AB  - Even when people with schizophrenia describe themselves as generally motivated
      and eager to engage in activities, they may not actually be motivated in the
      present moment. In order to better understand the relationship between trait and
      state motivation, we aimed to assess trait motivation and state intrinsic
      motivation, and investigate their relations to each other and to criterion
      related variables including cognition, negative symptoms, and beliefs about one's
      own competency-also known as perceived competency (PC). Further, we investigated
      whether PC mediates the relationships between state intrinsic motivation (IM) and
      trait motivation dimensions. Forty individuals with schizophrenia or
      schizoaffective disorders were administered two self-report measures of
      motivation, the Motivational Trait Questionnaire (Kanfer, R., Ackerman, P., 2000.
      Individual differences in work motivation: further explorations of a trait
      framework. Appl. Psychol. 49 (3), 470-482) and the Intrinsic Motivation Inventory
      for Schizophrenia Research (Choi, J., Medalia, A., 2010. Intrinsic motivation and
      learning in a schizophrenia spectrum sample. Schizophr. Res. 118, 12-19), as well
      as measures of PC, cognition and symptoms. The results showed that in people with
      schizophrenia, trait approach motivation, but not trait avoidance motivation, is
      positively correlated with state intrinsic motivation and PC. There was evidence
      that PC partially mediates the relationship between trait approach motivation and
      state intrinsic motivation to do the task. These results support the role of
      therapies that directly address self-competency beliefs and set the groundwork
      for future investigations on the impact of such treatments on motivation.

PMID- 22627104
TI  - Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil
      and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer:
      initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial.
AB  - BACKGROUND: Preoperative chemoradiotherapy, total mesorectal excision surgery,
      and adjuvant chemotherapy with fluorouracil is the standard combined modality
      treatment for rectal cancer. With the aim of improving disease-free survival
      (DFS), this phase 3 study (CAO/ARO/AIO-04) integrated oxaliplatin into standard
      treatment. METHODS: This was a multicentre, open-label, randomised, phase 3 study
      in patients with histologically proven carcinoma of the rectum with clinically
      staged T3-4 or any node-positive disease. Between July 25, 2006, and Feb 26,
      2010, patients were randomly assigned to two groups: a control group receiving
      standard fluorouracil-based combined modality treatment, consisting of
      preoperative radiotherapy of 50.4 Gy plus infusional fluorouracil (1000 mg/m(2)
      days 1-5 and 29-33), followed by surgery and four cycles of bolus fluorouracil
      (500 mg/m(2) days 1-5 and 29; fluorouracil group); and an experimental group
      receiving preoperative radiotherapy of 50.4 Gy plus infusional fluorouracil (250
      mg/m(2) days 1-14 and 22-35) and oxaliplatin (50 mg/m(2) days 1, 8, 22, and 29),
      followed by surgery and eight cycles of adjuvant chemotherapy with oxaliplatin
      (100 mg/m(2) days 1 and 15), leucovorin (400 mg/m(2) days 1 and 15), and
      infusional fluorouracil (2400 mg/m(2) days 1-2 and 15-16; fluorouracil plus
      oxaliplatin group). Randomisation was done with computer-generated block
      randomisation codes stratified by centre, clinical T category (cT1-4 vs cT4), and
      clinical N category (cN0 vs cN1-2) without masking. DFS is the primary endpoint.
      Secondary endpoints, including toxicity, compliance, and histopathological
      response are reported here. Safety and compliance analyses included patients as
      treated, efficacy endpoints were analysed according to the intention-to-treat
      principle. This study is registered with ClinicalTrials.gov, number NCT00349076.
      FINDINGS: Of the 1265 patients initially enrolled, 1236 were evaluable (613 in
      the fluorouracil plus oxaliplatin group and 623 in the fluorouracil group).
      Preoperative grade 3-4 toxic effects occurred in 140 (23%) of 606 patients who
      actually received fluorouracil and oxaliplatin during chemoradiotherapy and in
      127 (20%) of 624 patients who actually received fluorouracil chemoradiotherapy.
      Grade 3-4 diarrhoea was more common in those who received fluorouracil and
      oxaliplatin during chemoradiotherapy than in those who received fluorouracil
      during chemoradiotherapy (73 patients [12%] vs 52 patients [8%]), as was grade 3
      4 nausea or vomiting (23 [4%] vs nine [1%]). 516 (85%) of the 606 patients who
      received fluorouracil and oxaliplatin-based chemoradiotherapy had the full dose
      of chemotherapy, and 571 (94%) had the full dose of radiotherapy; as did 495
      (79%) and 601 (96%) of 624 patients who received fluorouracil-based
      chemoradiotherapy, respectively. A pathological complete response was achieved in
      103 (17%) of 591 patients who underwent surgery in the fluorouracil and
      oxaliplatin group and in 81 (13%) of 606 patients who underwent surgery in the
      fluorouracil group (odds ratio 1.40, 95% CI 1.02-1.92; p=0.038). In the
      fluorouracil and oxaliplatin group, 352 (81%) of 435 patients who began adjuvant
      chemotherapy completed all cycles (with or without dose reduction), as did 386
      (83%) of 463 patients in the fluorouracil group. INTERPRETATION: Inclusion of
      oxaliplatin into modified fluorouracil-based combined modality treatment was
      feasible and led to more patients achieving a pathological complete response than
      did standard treatment. Longer follow-up is needed to assess DFS. FUNDING: German
      Cancer Aid (Deutsche Krebshilfe).

PMID- 22627124
TI  - Flat affect and social functioning: a 10 year follow-up study of first episode
      psychosis patients.
AB  - BACKGROUND: Affective flattening has been described as enduring, but long term
      follow-up studies of first episode psychosis patients are lacking. OBJECTIVE: The
      aim of this study was to follow the symptom development of flat affect (FA), over
      a 10 year follow-up period, with focus on prevalence, predictors and outcome
      factors including social functioning. METHODS: Three-hundred-and-one patients
      with FEP were included at baseline, 186 participated in the 10 year follow-up.
      These were followed on PANSS item N1 (FA) from baseline through 5 follow-up
      assessments over 10 years. Patients were grouped as having never-present,
      improving, deteriorating, fluctuating or enduring FA. The groups were compared on
      baseline variables, variables at 10 year follow-up, and social functioning
      throughout the follow-up period. RESULTS: Twenty nine percent never displayed FA,
      66% had improving, deteriorating or fluctuating FA, while 5% of patients had
      enduring FA. Premorbid social function predicted enduring FA. The patients with
      enduring, fluctuating and deteriorating FA did poorer on all outcome variables,
      including remission and recovery rates. The enduring FA group did significantly
      poorer in social functioning over the 10 year period. CONCLUSIONS: FA is
      expressed at some point of time in the majority of FEP patients in a 10 year
      follow-up period, and appears more fluctuant than expected from the relevant
      literature. FA is associated with poorer outcome after 10 years, and enduring FA
      to poorer social function at all points of assessment.

PMID- 22627123
TI  - Adolescents at ultra-high risk for psychosis with and without 22q11 deletion
      syndrome: a comparison of prodromal psychotic symptoms and general functioning.
AB  - OBJECTIVE: Genetic syndromes related to psychosis have become increasingly
      important for exploring the trajectory that leads to psychosis onset. A very
      significant opportunity for mapping earlier phases of the trajectory can be found
      in 22q11.2 deletion syndrome (22q11DS). Comparative studies have shown that
      schizophrenic disorder in 22q11DS largely resembles schizophrenia in the general
      population, but only few studies have investigated the features of prodromal
      symptoms in 22q11DS. The aim of the present study was to investigate differences
      and similarities between two samples: patients with 22q11DS clinically at risk
      for psychotic onset (UHR+22q11DS group) and patients at clinical high risk for
      psychotic onset (UHR group). METHOD: The study was conducted on a sample of 30
      individuals UHR+22q11DS and 81 individuals at UHR without 22q11DS. The two groups
      were compared on positive, negative and depressive symptoms, level of general
      functioning and IQ. RESULTS: There was a significant group difference in negative
      symptoms, but no significant differences were found for positive, global and
      total symptoms. The UHR+22q11DS group showed a lower level of general
      functioning. The clinical profile of the UHR+22q11DS group was clearly more
      homogeneous. CONCLUSIONS: Even if the two UHR groups are comparable in terms of
      positive symptoms, the UHR+22q11DS have a specific clinical pattern characterized
      by higher negative symptoms, lower general functioning and an older age of onset
      of the UHR state. This finding may be of clinical value for the development of
      specific therapeutic intervention for UHR+22q11DS, and of theoretical value since
      the two groups may share only some underlying etiopathogenetic mechanisms.

PMID- 22627125
TI  - Heritability of functioning in families with schizophrenia in relation to
      neurocognition.
AB  - The role of daily functioning is an integral part of the schizophrenia (SZ)
      phenotype and deficits in this trait appear to be present in both affected
      persons and some unaffected relatives; hence we have examined its heritability in
      our cohort of African American schizophrenia families. There is now ample
      evidence that deficits in cognitive function can impact family members who are
      not themselves diagnosed with SZ; there is some, but less evidence that role
      function behaves likewise. We evaluate whether role function tends to "run in
      families" who were ascertained because they contain an African American proband
      diagnosed with SZ. METHODS: We analyzed heritability for selected traits related
      to daily function, employment, living situation, marital status, and Global
      Assessment Scale (GAS) score; modeling age, gender, along with neurocognition and
      diagnosis as covariates in a family based African-American sample (N=2488
      individuals including 979 probands). RESULTS: Measures of role function were
      heritable in models including neurocognitive domains and factor analytically
      derived neurocognitive summary scores and demographics as covariates; the most
      heritable estimate was obtained from the current GAS scores (h2=0.72).
      Neurocognition was not a significant contributor to heritability of role
      function. CONCLUSIONS: Commonly assessed demographic and clinical indicators of
      functioning are heritable with a global rating of functioning being the most
      heritable. Measures of neurocognition had little impact on heritability of
      functioning overall. The family covariance for functioning, reflected in its
      heritability, supports the concept that interventions at the family level, such
      as evidenced-based family psychoeducation may be beneficial in schizophrenia.

PMID- 22627128
TI  - Comparative genomic analysis reveals novel facts about Leptospirillum spp.
      cytochromes.
AB  - Chemolithoautotrophic acidophilic bacteria, which belong to the genus
      Leptospirillum, can only grow with Fe(II) as electron donor and oxygen as an
      electron acceptor. Members of this genus play an important role in bioleaching
      sulfide ores. We used nearly complete genome sequences of Leptospirillum
      ferrooxidans (group I), Leptospirillum rubarum, Leptospirillum '5-way CG' (group
      II) and Leptospirillum ferrodiazotrophum (group III) to identify cytochromes that
      are likely involved in electron transfer chain(s). The results show the presence
      of genes encoding a number of c-type cytochromes (18-20 genes were identified in
      each species), as well as bd and cbb3 oxidases. Genes encoding cbb3 oxidase are
      clustered, with predicted genes involved in cbb3 maturation proteins. Duplication
      of cbb3 encoding genes (ccoNO) was detected in all four genomes. Interestingly,
      these micro-organisms also contain genes that potentially encode bc1 and b6f-like
      complexes organized into two putative operon structures. To date, the
      Leptospirillum genus includes the only organisms reported to have genes coding
      for two different bc complexes. This study provides detailed insights into the
      components of electron transfer chains of Leptospirillum spp., revealing their
      conservation among leptospirilla groups and suggesting that there may be a single
      common pathway for electron transport between Fe(II) and oxygen.

PMID- 22627126
TI  - Identification and characterization of DSCAM isoforms isolated from orange
      spotted grouper Epinephelus coioides.
AB  - The Down syndrome cell adhesion molecule (DSCAM), an immunoglobulin (Ig)
      superfamily member, was first identified from human and subsequently isolated
      from both vertebrates and invertebrates. Recent studies have shown that the DSCAM
      molecule serves diverse functions in neurodevelopment, such as axon guidance and
      neuronal migration. Most studies on DSCAM, however, have focused on mammals and
      arthropods, and our present knowledge of bony fish DSCAM is still limited. In
      this study, orange-spotted grouper Epinephelus coioides was used as an animal
      model to explore the possible functions of DSCAM. Two DSCAM isoforms were
      isolated, namely EcDSCAM A and EcDSCAM B, with lengths of 1648 and 2025 amino
      acids, respectively. The classical domain structure (i.e. 9Ig-4FNIII-1Ig-2FNIII
      Transmembrane domain-Cytoplasmic tail) was also found in the coding regions of
      these two EcDSCAMs. Phylogenetic analysis showed that in the vertebrate DSCAM
      clade, the EcDSCAMs and various teleost DSCAMs were clustered into a subclade.
      Real-time PCR revealed that EcDSCAM B is the major EcDSCAM isoform, with the
      expression of EcDSCAM B being significantly higher than that of EcDSCAM A. During
      the first 14days after hatching (dph), increases in the expression of the two
      EcDSCAMs were observed at 2-4 and 8-11dph. EcDSCAM is expressed mainly in the
      intestine, nerve-related tissues, and stomach. Optic nerve transection analysis
      showed that EcDSCAM was up-regulated during optic nerve regeneration after optic
      nerve injury. We also investigated whether DSCAM expression was affected by viral
      nervous necrosis (VNN) disease or vibriosis. We found that when grouper were
      challenged with nervous necrosis virus (NNV), there were no meaningful changes in
      DSCAM expression, but challenge with Vibrio anguillarum led to a decrease in
      EcDSCAM levels in the brain. This decrease may be related to the pathogenesis of
      V. anguillarum.

PMID- 22627127
TI  - Thulium laser (Revolix) vapoenucleation of the prostate is a safe procedure in
      patients with an increased risk of hemorrhage.
AB  - PURPOSE: To evaluate the feasibility and safety of thulium:yttrium-aluminium
      garnet laser vapoenucleation of the prostate (ThuVEP) in patients with chronic
      anticoagulation and bleeding disorders. METHODS: We retrospectively analyzed the
      clinical data (transfusion rate, hemoglobin changes, residual urine, bleeding
      complications, complications and residual urine) of patients with chronic
      anticoagulation and bleeding disorders treated with ThuVEP. Anticoagulation was
      not paused for surgery. RESULTS: We identified 39 patients who fulfilled the
      inclusion criteria (32 with chronic anticoagulation, 3 with bleeding disorder,
      and 4 with both). Mean preoperative hemoglobin was 12.9 g/l; the postoperative
      hemoglobin was 11.7 g/l. One patient received a blood transfusion. Mean residual
      urine was 166 ml preoperatively and 47 ml postoperatively, respectively;
      spontaneous voiding postoperatively was feasible in 36 patients. During follow
      up, 5 patients suffered from gross hematuria, which was treated conservatively.
      CONCLUSIONS: ThuVEP is a safe procedure in patients with therapeutic
      anticoagulation, bleeding disorders and platelet aggregation inhibitor
      medication.

PMID- 22627129
TI  - Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases.
AB  - Lysophosphatidic acid (LPA) designates a family of bioactive phosphoglycerides
      that differ in the length and degree of saturation of their radyl chain.
      Additional diversity is provided by the linkage of the radyl chain to glycerol:
      acyl, alkyl, or alk-1-enyl. Acyl-LPAs are the predominate species in tissues and
      biological fluids. Alkyl-LPAs exhibit distinct pharmacodynamics at LPA receptors,
      potently drive platelet aggregation, and contribute to ovarian cancer
      aggressiveness. Multiple biosynthetic pathways exist for alkyl-LPA production.
      Herein we report that diacylglycerol kinases (DGKs) contribute to cell-associated
      alkyl-LPA production involving phosphorylation of 1-alkyl-2-acetyl glycerol and
      document the biosynthesis of alkyl-LPA by DGKs in SKOV-3 ovarian cancer cells,
      specifically identifying the contribution of DGKalpha. Concurrently, we
      discovered that treating SKOV-3 ovarian cancer cell with a sphingosine analog
      stimulates conversion of exogenous 1-alkyl-2-acetyl glycerol to alkyl-LPA,
      indicating that DGKalpha contributes significantly to the production of alkyl-LPA
      in SKOV-3 cells and identifying cross-talk between the sphingolipid and glycerol
      lipid pathways.

PMID- 22627130
TI  - Deregulation of Beclin 1 in patients with tobacco-related oral squamous cell
      carcinoma.
AB  - Autophagy is a physiologically regulated and evolutionary conserved process that
      plays a critical role in degradation of cytoplasmic proteins and other
      macromolecules within the lysosomes. Beclin-1, the mammalian orthologue of yeast
      Atg6, is an important mediator of autophagy that has been studied in many human
      cancers. However, the expression of Beclin-1 has not yet been investigated in
      oral cancer. We for the first time investigated the expression of Beclin-1 in
      serum and tissues and correlated it with the clinic-pathological features of oral
      cancer patients. m-RNA expression of Beclin-1 was evaluated in tumor and normal
      areas of surgical specimens from 10 oral cancer patients by real-time PCR.
      Approximately, 8-fold lower expression (p<0.001) of Beclin-1 mRNA was observed in
      tumor tissue as compared to the normal tissue. Serum levels of Beclin-1 were
      evaluated by SPR and ELISA. No significant difference was observed in serum
      Beclin-1 levels in patients as compared to healthy subjects, similarly no
      correlation was found between serum levels and clinic-pathological parameters
      such as stage, lymph node involvement and tumor size. Our results demonstrate
      that down-regulation of Beclin-1 may play an important role in the development
      and progression of oral cancer possibly by dysregulation of autophagy in tumor
      cells.

PMID- 22627131
TI  - Sodium arsenite down-regulates the expression of X-linked inhibitor of apoptosis
      protein via translational and post-translational mechanisms in hepatocellular
      carcinoma.
AB  - X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitors of
      apoptosis protein (IAP) family, and has been reported to exhibit elevated
      expression levels in hepatocellular carcinoma (HCC) and promote cell survival,
      metastasis and tumor recurrence. Targeting XIAP has proven effective for the
      inhibition of cancer cell proliferation and restoration of cancer cell
      chemosensitivity. Arsenic (or sodium arsenite) is a potent anti-tumor agent used
      to treat patients with acute promyelocytic leukemia (APL). Additionally, arsenic
      induces cell growth inhibition, cell cycle arrest and apoptosis in human HCC
      cells. In this study, we identified XIAP as a target for sodium arsenite-induced
      cytotoxicity in HCC. The exposure of HCC cell lines to sodium arsenite resulted
      in inhibition of XIAP expression in both a dose- and time-dependent manner.
      Sodium arsenite blocked the de novo XIAP synthesis and the activity of its
      internal ribosome entry site (IRES) element. Moreover, treatment with sodium
      arsenite decreased the protein stability of XIAP and induced its ubiquitin
      proteasomal degradation. Overexpression of XIAP attenuated the pro-apoptotic
      effect of sodium arsenite in HCC. Taken together, our data demonstrate that
      sodium arsenite suppresses XIAP expression via translational and post
      translational mechanisms in HCC.

PMID- 22627132
TI  - Endoplasmic reticulum chaperone GRP78 suppresses the aggregation of proteins
      containing expanded polyglutamine tract.
AB  - Polyglutamine (polyQ) diseases are inherited neurodegenerative diseases
      characterized by the aggregation of proteins containing expanded polyQ tract. It
      has been shown that expanded polyQ tract-containing proteins impair the functions
      of other cellular proteins. However, quantitative changes of cellular proteins in
      cells expressing expanded polyQ tract-containing proteins have not been
      performed. Here, we performed proteomic analysis of cells expressing expanded
      polyQ tract-containing proteins, and showed that GRP78, the endoplasmic reticulum
      (ER) chaperone, was significantly decreased in the cells expressing enhanced
      green fluorescent protein with a pathological-length polyQ tract (EGFP-polyQ97),
      but not with a non-pathological-length polyQ tract (EGFP-polyQ24). In addition,
      we revealed that down-regulation of GRP78 expression resulted in increase of the
      aggregation of EGFP-polyQ97. Conversely, the aggregation of EGFP-polyQ97 was
      suppressed by the overexpression of GRP78 in the cells. Furthermore, it seemed
      that the decreased GRP78 expression in the cells expressing EGFP-polyQ97 was due
      to the enhanced protein degradation of GRP78 through the ubiquitin-proteasome
      pathway. These findings indicated that GRP78, which has an inhibitory effect on
      the aggregation of proteins containing expanded polyQ tract, may be an effective
      target for the treatment of polyQ diseases.

PMID- 22627133
TI  - The subcellular localization of cyclin B2 is required for bipolar spindle
      formation during Xenopus oocyte maturation.
AB  - Cyclins B1 and B2 are subtypes of cyclin B, a regulatory subunit of a
      maturation/M-phase promoting factor, and they are also highly conserved in many
      vertebrate species. Cyclin B1 is essential for mitosis, whereas cyclin B2 is
      regarded as dispensable. However, the overexpression of the cyclin B2 N-terminus
      containing the cytoplasmic retention signal, but not cyclin B1, inhibits bipolar
      spindle formation in Xenopus oocytes and embryos. Here we show that endogenous
      cyclin B2 was localized in and around the germinal vesicle. The perinuclear
      localization of cyclin B2 was perturbed by the overexpression of its N-terminus
      containing the cytoplasmic retention signal, which resulted in a spindle defect.
      This spindle defect was rescued by the overexpression of bipolar kinesin Eg5,
      which is located at the perinuclear region in the proximity of endogenous cyclin
      B2. These results demonstrate that the proper localization of cyclin B2 is
      essential for bipolar spindle formation in Xenopus oocytes.

PMID- 22627134
TI  - Purification and crystallization of the ABC-type transport substrate-binding
      protein OppA from Thermoanaerobacter tengcongensis.
AB  - Di- and oligopeptide- binding protein OppAs play important roles in solute and
      nutrient uptake, sporulation, biofilm formation, cell wall muropeptides
      recycling, peptide-dependent quorum-sensing responses, adherence to host cells,
      and a variety of other biological processes. Soluble OppA from Thermoanaerobacter
      tengcongensis was expressed in Escherichia coli. The protein was found to be >95%
      pure with SDS-PAGE after a series of purification steps and the purity was
      further verified by mass spectrometry. The protein was crystallized using the
      sitting-drop vapour-diffusion method with PEG 400 as the precipitant. Crystal
      diffraction extended to 2.25 A. The crystal belonged to space group C222(1), with
      unit-cell parameters of a=69.395, b=199.572, c=131.673 A, and alpha=beta=gamma=90
      degrees .

PMID- 22627135
TI  - DNA methyltransferase inhibitor CDA-II inhibits myogenic differentiation.
AB  - CDA-II (cell differentiation agent II), isolated from healthy human urine, is a
      DNA methyltransferase inhibitor. Previous studies indicated that CDA-II played
      important roles in the regulation of cell growth and certain differentiation
      processes. However, it has not been determined whether CDA-II affects skeletal
      myogenesis. In this study, we investigated effects of CDA-II treatment on
      skeletal muscle progenitor cell differentiation, migration and proliferation. We
      found that CDA-II blocked differentiation of murine myoblasts C2C12 in a dose
      dependent manner. CDA-II repressed expression of muscle transcription factors,
      such as Myogenin and Mef2c, and structural proteins, such as myosin heavy chain
      (Myh3), light chain (Mylpf) and MCK. Moreover, CDA-II inhibited C1C12 cell
      migration and proliferation. Thus, our data provide the first evidence that CDA
      II inhibits growth and differentiation of muscle progenitor cells, suggesting
      that the use of CDA-II might affect skeletal muscle functions.

PMID- 22627136
TI  - Changes of calcium channel mRNA, protein and current in NG108-15 cells after cell
      differentiation.
AB  - Based on the characteristics of differentiated NG108-15 cells (cell membrane
      excitability, acetylcholine release, and activities of choline acetyltransferase
      and acetylcholinesterase), NG108-15 cells are extensively used to explore
      neuronal functions as a cholinergic cell line. In the present study,
      differentiation-induced alterations of voltage-gated Ca(2+) channel mRNA,
      protein, and current were investigated in the NG108-15 cells. Real-time PCR,
      Western blot, and whole-cell patch-clamp data showed that differentiation caused
      mRNA, protein, and ion current changes of all Ca(2+) channel subunits. However,
      the changes of mRNA, protein, and ion current are inconsistent in all Ca(2+)
      channel subunits. Especially, P/Q- and R-type Ca(2+) channel proteins do not form
      the functional P/Q- and R-type Ca(2+) channels even if the mRNA and protein of
      P/Q- and R-type Ca(2+) channels can be detected in NG108-15 cells. These results
      indicate that differentiation can modulate gene transcription, protein
      translation, and post-translation of the Ca(2+) channels to induce the alteration
      of the Ca(2+) ion currents in NG108-15 cells. From these data, we understand that
      combining real-time PCR, Western blot, and patch-clamp techniques can
      comprehensively unveil the modulation of the Ca(2+) channels.

PMID- 22627137
TI  - Reduction of DNA hydroxymethylation in the mouse kidney insulted by ischemia
      reperfusion.
AB  - Ischemia reperfusion (IR) is a frequent pathological injury to the perioperative
      patients. The molecular mechanism underlying IR injury is still not well
      characterized. In this study, we investigated the effect of IR injury on DNA
      hydroxymethylation in mouse kidney. Dot blot and immunochemistry analysis showed
      that the global level of 5-hydroxymethylcytosine (5hmC) was reduced in mouse
      kidney insulted by IR; however, the 5-methylcytosine (5mC) level had no
      significant change. hMeDIP-qPCR validated that IR injury also decreased the 5hmC
      enrichment at promoter regions of Cxcl10 and Ifngr2 genes. RT-qPCR analysis
      revealed that the mRNA levels of Cxcl10 and Ifngr2 increased in IR-injured
      kidney. In addition, mRNA expression of both Tet1 and Tet2 but not Tet3 was
      dramatically downregulated in IR-injured kidney. Taken together, our data
      provided the first evidence that IR injury influences DNA hydroxymethylation and
      Tet gene expression in mouse kidney, which may contribute to the regulation of
      gene transcription during renal IR injury.

PMID- 22627138
TI  - The interaction between hepatitis B virus X protein and AIB1 oncogene is required
      for the activation of NFkappaB signal transduction.
AB  - We identified the interaction between HBV X (HBx) protein and the oncogene AIB1
      (amplified in breast cancer 1). A serine/proline motif (SSPSPS) in HBx was found
      to be required for the interaction. Two LXD motifs [LLXX(X)L, X means any amino
      acids], LLRNSL and LLDQLHTLL in AIB1 were also found to be involved in the HBx
      AIB1 interaction. The HBx-AIB1 interaction was important for the activation of
      NFkappaB signal transduction, the HBx mutant that did not interact with
      AIB1showed dramatically lower NFkappaB activation activity than the WT HBx. These
      findings contribute to the new understanding on signal transduction activation
      mechanisms of HBx.

PMID- 22627139
TI  - AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of
      Arabidopsis in abscisic acid-dependent manner.
AB  - AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as
      an abiotic stress candidate gene by bioinformatic analysis in our previous study.
      The gene encodes a putative protein phosphatase 2C that belongs to Group G of
      PP2C. There is no report of Group G genes involved in abiotic stress so far. Real
      time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt,
      drought, and abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in
      the ABA synthesis-deficient mutant abi2-3 were much lower than that in WT plants
      under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA
      dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance,
      whereas its loss of function caused decreased salt tolerance. These results
      indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent
      manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of
      stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity
      was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter
      GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm
      via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.

PMID- 22627140
TI  - Pyruvate kinase M2 promotes the growth of gastric cancer cells via regulation of
      Bcl-xL expression at transcriptional level.
AB  - PKM2 is an isoenzyme of the glycolytic enzyme pyruvate kinase that promotes
      aerobic glycolysis. Here, we describe an important role for PKM2 in regulating
      the survival of gastric cancer (GC) cells. We showed that PKM2 was overexpressed
      in gastric tumor tissues compared to normal tissues and its expression level was
      associated with poor survival of gastric cancer patients. We also showed that
      PKM2 affected cell survival by regulating Bcl-xL at the transcriptional level.
      PKM2 knockdown partially affected the stability of NF-kB subunit p65, suggesting
      that post-translational regulation of p65 by PKM2 is one of plausible mechanisms
      for the increased cell growth. Therefore, PKM2 may function as an upstream
      molecule that regulates p65 function and thus enhances the growth of tumor cells.

PMID- 22627141
TI  - Phosphorylation and activation of nuclear Ca2+/calmodulin-dependent protein
      kinase phosphatase (CaMKP-N/PPM1E) by Ca2+/calmodulin-dependent protein kinase I
      (CaMKI).
AB  - Nuclear Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP-N/PPM1E) is
      an enzyme that dephosphorylates and downregulates multifunctional
      Ca(2+)/calmodulin-dependent protein kinases (CaMKs) as well as AMP-dependent
      protein kinase. In our previous study, we found that zebrafish CaMKP-N (zCaMKP-N)
      underwent proteolytic processing and translocated to cytosol in a proteasome
      inhibitor-sensitive manner. In the present study, we found that zCaMKP-N is
      regulated by phosphorylation at Ser-480. When zCaMKP-N was incubated with the
      activated CaMKI, time-dependent phosphorylation of the enzyme was observed. This
      phosphorylation was significantly reduced when Ser-480 was replaced by Ala,
      suggesting that CaMKI phosphorylates Ser-480 of zCaMKP-N. Phosphorylation-mimic
      mutants, S480D and S480E, showed higher phosphatase activities than those of wild
      type and S480A mutant in solution-based phosphatase assay using various
      substrates. Furthermore, autophosphorylation of CaMKII after ionomycin treatment
      was more severely attenuated in Neuro2a cells when CaMKII was cotransfected with
      the phosphorylation-mimic mutant of zCaMKP-N than with the wild-type or non
      phosphorylatable zCaMKP-N. These results strongly suggest that phosphorylation of
      zCaMKP-N at Ser-480 by CaMKI activates CaMKP-N catalytic activity and thereby
      downregulates multifunctional CaMKs in the cytosol.

PMID- 22627142
TI  - Subchronic ketamine treatment leads to permanent changes in EEG, cognition and
      the astrocytic glutamate transporter EAAT2 in mice.
AB  - Ketamine is an NMDA receptor antagonist with psychotomimetic, dissociative,
      amnestic and euphoric effects. When chronically abused, ketamine users display
      deficits in cognition and information processing, even following long-term
      abstinence from the drug. While animal studies have shown evidence of behavioral
      changes and cognitive deficits that mimic those seen in humans within the period
      immediately following subchronic ketamine, a few animal studies have assessed
      long-term changes following cessation of ketamine exposure. To this end, the
      present study assessed event related potentials (ERPs) and EEG oscillations in
      mice exposed to subchronic ketamine following a 6month period of abstinence from
      the drug. Ketamine-treated mice showed no change in P20, but did show marked
      reductions in amplitude of the later N40 and P80 components, consistent with
      previous studies of acute ketamine exposure. Additionally, ketamine-treated
      animals showed a significant reduction in stimulus evoked theta oscillations. To
      assess the functional significance of these changes, mice were also assessed on a
      series of behavioral and cognitive tests, including progressive ratio
      (motivation), extinction (behavioral flexibility) and win-shift radial maze
      (spatial memory). Subchronic ketamine produced marked disruptions in reversal
      learning and spatial memory. Analysis of brains from ketamine-treated mice failed
      to show evidence of neuronal degeneration as determined by NueN
      immunohistochemistry, but did show increased astrocyte proliferation and
      decreased expression of the glial specific glutamate transporter, GLT-1. These
      results strongly suggest: 1) that subchronic ketamine induces significant changes
      in brain function that long exceed exposure to the drug; 2) that ketamine
      exposure in mice induces lasting cognitive impairments closely resembling those
      observed in human ketamine abusers; 3) that ERP and EEG measures are highly
      sensitive to alterations in brain function associated with reduced cognitive
      function; and 4) that the brain changes induced by chronic ketamine treatment are
      suggestive of long-term adaptive or plastic, rather than degenerative, changes.

PMID- 22627144
TI  - Comparisons of forward and backward gait between poorer and better attention
      capabilities in early Parkinson's disease.
AB  - This study compared forward and backward gait between Parkinson's disease (PD)
      patients with poorer and better attention capabilities. PD and healthy control
      (HC) participants received a dual-stimuli attention task. The results were
      assessed using principal component analysis to quantify and rank attention
      capability. Accordingly, 22 PD and 42 HC subjects were equally divided into
      poorer (14 PD-P, 18 HC-P) and better (8 PD-B, 24 HC-B) attention capabilities. To
      analyze the spatiotemporal gait parameters, each participant walked forwards and
      backwards on a GAITRite((r)) walkway. Compared to HC, PD performed worse in the
      dual task and exhibited slower velocity, less swing, and shorter stride in both
      walking directions. Notably, PD-P experienced all these gait defects, regardless
      of directions. PD-B walked worse than HC-B backwards, and displayed comparable
      gait to HC-P in both directions. In PD and HC, velocity, stride, and swing
      decreased perceptibly when walking backwards compared to forwards, and the same
      was true for velocity and stride in PD-P and PD-B. Backward strides were reduced
      evidently more in PD-P than in PD-B. However, backward swing reductions in PD-P
      and PD-B were statistically insignificant. Cadence in both directions was similar
      within the groups and between the groups, and there were little alterations
      between directions within each group and between groups. These results suggest
      that attention capability may affect PD gait. Poorer attention exacerbates gait
      defects and better attention improves gait in both directions. These results may
      support the application of cuing strategies in PD to enhance attention capability
      and improve walking gait.

PMID- 22627143
TI  - Effects of histone acetylation and CpG methylation on the structure of
      nucleosomes.
AB  - Nucleosomes are the fundamental packing units of the eukaryotic genome. A
      nucleosome core particle comprises an octameric histone core wrapped around by
      ~147bp DNA. Histones and DNA are targets for covalent modifications mediated by
      various chromatin modification enzymes. These modifications play crucial roles in
      various gene regulation activities. A group of common hypotheses for the
      mechanisms of gene regulation involves changes in the structure and structural
      dynamics of chromatin induced by chromatin modifications. We employed single
      molecule fluorescence methods to test these hypotheses by monitoring the
      structure and structural dynamics of nucleosomes before and after histone
      acetylation and DNA methylation, two of the best-conserved chromatin
      modifications throughout eukaryotes. Our studies revealed that these
      modifications induce changes in the structure and structural dynamics of
      nucleosomes that may contribute directly to the formation of open or repressive
      chromatin conformation.

PMID- 22627145
TI  - A qualitative study examining women's experiences of an appearance-focussed
      facial-ageing sun protection intervention.
AB  - The study was designed to investigate women's experiences of an appearance
      focussed, facial-ageing, morphing intervention to show the effect of UV exposure
      on their skin. Forty-seven women aged 18-34 took part in the intervention: 35
      women in individual sessions, and 12 in four focus groups. Transcripts were
      analysed using inductive thematic analysis. Women were shocked about the likely
      effect of UV exposure on their skin. All of the women stated that they were going
      to make changes to their UV exposure and sun protection behaviours after viewing
      the images of themselves which were morphed to show the effects of UV exposure.
      The results are discussed in relation to suggestions for interventions aimed at
      women aged 18-34. It is concluded that appearance-based interventions do have a
      role to play in healthcare and educational settings with regards to UV exposure
      and sun protection intentions.

PMID- 22627146
TI  - Endoscopic ultrasound-guided transrectal drainage of a pelvic abscess following
      total abdominal hysterectomy.

PMID- 22627147
TI  - Regulation of CREB signaling through L-type Ca2+ channels by Nipsnap-2.
AB  - A recent study identified Nipsnap1 as an auxiliary protein inhibiting TRPV6 ion
      channel activity. Based upon this finding, we investigated the role of Nipsnap1,
      and the closely related Nipsnap2, in Ca(2+) channel regulation. Here, we find
      that overexpression of Nipsnap2 caused a 45% increase in currents though L-type
      Ca(2+) channels in a neuronal cell line, while siRNA knockdown of Nipsnap2
      greatly reduced L-type currents. The increased influx through L-type Ca(2+)
      channels due to Nipsnap2 overexpression led to increased phosphorylation of the
      transcription factor cyclic adenosine monophosphate (cAMP) response element
      binding protein (CREB) along with enhanced expression of several transcription
      factors and CREB target genes. These experiments highlight a novel role of
      Nipsnap2 in transcriptional regulation via L-type Ca(2+) channels.

PMID- 22627148
TI  - Chronic pregabalin inhibits synaptic transmission between rat dorsal root
      ganglion and dorsal horn neurons in culture.
AB  - In this study, we have examined the properties of synaptic transmission between
      dorsal root ganglion (DRG) and dorsal horn (DH) neurons, placed in co-culture. We
      also examined the effect of the anti-hyperalgesic gabapentinoid drug pregabalin
      (PGB) at this pharmacologically relevant synapse. The main method used was
      electrophysiological recording of excitatory post synaptic currents (EPSCs) in DH
      neurons. Synaptic transmission between DRG and DH neurons was stimulated by
      capsaicin, which activates transient receptor potential vanilloid-1 (TRPV1)
      receptors on small diameter DRG neurons. Capsaicin (1 MUM) application increased
      the frequency of EPSCs recorded in DH neurons in DRG-DH co-cultures, by about 3
      fold, but had no effect on other measured properties of the EPSCs. There was also
      no effect of capsaicin in the absence of co-cultured DRGs. Application of PGB
      (100 MUM) for 40-48 h caused a reduction in the capsaicin-induced increase in
      EPSC frequency by 57%. In contrast, brief preincubation of PGB had no significant
      effect on the capsaicin-induced increase in EPSC frequency. In conclusion, this
      study shows that PGB applied for 40-48 h, but not acute application inhibits
      excitatory synaptic transmission at DRG-DH synapses, in response to nociceptive
      stimulation, most likely by a presynaptic effect on neurotransmitter release from
      DRG presynaptic terminals.

PMID- 22627149
TI  - Posterior pituitary functions are not altered after growth hormone replacement
      therapy in hypopituitarism due to Sheehan's syndrome.
AB  - OBJECTIVE: The aim of the present study was to investigate the effects of growth
      hormone (GH) replacement on posterior pituitary functions of GH-deficient
      Sheehan's syndrome (SS) patients. DESIGN: Ten patients with SS and 14 healthy
      control women were included in this prospective study. All patients were given
      appropriate hormone replacement therapy other than GH, according to present
      hormone deficiencies. Patients were euthyroid and eucortisolemic at the time of
      baseline evaluation. Patients and the control group were evaluated with water
      deprivation and saline-infusion tests at baseline and the tests were repeated in
      patients with SS after 3 months of GH replacement therapy. RESULTS: According to
      the water deprivation test, 3 patients had partial central DI at baseline. Urine
      osmolalities of the patients were slightly lower and plasma osmolalities were
      significantly higher than the control group at baseline, after water deprivation
      and following DDAVP injection and after hypertonic saline infusion. The osmotic
      threshold of serum for thirst perception was found to be significantly higher in
      SS patients than the control group, GH replacement therapy did not influence the
      results of water deprivation and saline infusion tests in SS patients.
      CONCLUSION: Patients with SS have subtle abnormalities in posterior pituitary
      functions and the threshold for thirst perception is increased. However GH
      replacement therapy does not seem to reverse or adversely affect the mildly
      deteriorated posterior pituitary functions of SS patients.

PMID- 22627150
TI  - Voluntary GHG reduction of industrial sectors in Taiwan.
AB  - The present paper describes the voluntary greenhouse gas (GHG) reduction
      agreements of six different industrial sectors in Taiwan, as well as the
      fluorinated gases (F-gas) reduction agreement of the semiconductor and Liquid
      Crystal Display (LCD) industries. The operating mechanisms, GHG reduction
      methods, capital investment, and investment effectiveness are also discussed. A
      total of 182 plants participated in the voluntary energy saving and GHG reduction
      in six industrial sectors (iron and steel, petrochemical, cement, paper,
      synthetic fiber, and textile printing and dyeing), with 5.35 Mt reduction from
      2004 to 2008, or 33% higher than the target goal (4.02 Mt). The reduction
      accounts for 1.6% annual emission or 7.8% during the 5-yr span. The petrochemical
      industry accounts for 49% of the reduction, followed by the cement sector (21%)
      and the iron and steel industry (13%). The total investment amounted to
      approximately USD 716 million, in which, the majority of the investment went to
      the modification of the manufacturing process (89%). The benefit was valued at
      around USD 472 million with an average payback period of 1.5 yr. Moreover,
      related energy saving was achieved through different approaches, e.g., via
      electricity (iron and steel), steam and oil consumption (petrochemical) and coal
      usage (cement). The cost for unit CO(2) reduction varies per industry, with the
      steel and iron industrial sector having the highest cost (USD 346 t(-1) CO(2))
      compared with the average cost of the six industrial sectors (USD 134 t(-1)
      CO(2)). For the semiconductor and Thin-Film Transistor LCD industries, F-gas
      emissions were reduced from approximately 4.1 to about 1.7 Mt CO(2)-eq, and from
      2.2 to about 1.1 Mt CO(2)-eq, respectively. Incentive mechanisms for
      participation in GHG reduction are also further discussed.

PMID- 22627151
TI  - Evaluation of effectiveness of EDTA and sodium thiosulfate in removing metal
      toxicity toward sea urchin embryo-larval applying the TIE.
AB  - Since the development of the TIE (Toxicity Identification and Evaluation) in 1988
      it has been assumed that the capacity of EDTA and sodium thiosulfate to complex
      some metals, and thus remove their toxicity, can be applied to both freshwater
      and seawater ecotoxicological tests and the results subsequently interpreted.
      However, it is now known that there is a wide variability in the extent of this
      complexation. In this context, the removal of toxicity caused by the presence of
      Hg(2+), Cd(2+), Cu(2+), Cr(6+), Zn(2+), Ni(2+), Pb(2+), Ag(1+) and Se(2+),
      through metal complexation by EDTA and sodium thiosulfate, in relation to the
      performance of embryo-larval tests with the sea urchin Arbacia lixula was
      investigated. It was observed that EDTA was capable of removing the toxicity of
      Pb(2+), Zn(2+) and Cu(2+) while sodium thiosulfate only reduced the toxicity of
      Ag(1+). Compared to the complexation observed in freshwater ecotoxicological
      tests, the complexing agents used in this study (EDTA and sodium thiosulfate)
      have a lower capacity to complex metals in the marine ecotoxicological test with
      A. lixula.

PMID- 22627152
TI  - Assessment of phenylurea herbicides sorption on various Mediterranean soils
      affected by irrigation with wastewater.
AB  - The retention values of two herbicides, chlorotoluron and isoproturon, in five
      Mediterranean soils were assessed by two different approaches, a dynamic method,
      using a batch technique (BT) and a static method, using a soil saturated paste
      (SP). The SP method led in all cases to lower herbicide sorption when compared
      with BT, although pesticide distribution constants from both methods were
      linearly related for the set of used soils (R(2)?0.99) showing that both methods
      similarly reflected the behaviour of the different soils. Low-quality water,
      evaluated by employing recycled urban wastewater, did not modify herbicide
      sorption when compared with high quality water, in any soil and with any method.

PMID- 22627153
TI  - Magnetic ordering in semiconducting Tl0.53K0.47Fe1.64Se2 single crystals studied
      by Mossbauer spectroscopy.
AB  - The results of a 57Fe Mossbauer spectroscopy study between 4.5 and 523.2 K and in
      external magnetic fields (up to 90 kOe) of semiconducting Tl0.53K0.47Fe1.64Se2
      single crystals are reported. Evidence is provided for a possible phase
      separation into the magnetic majority and minority phases. It is demonstrated
      that the magnetic moments of the divalent Fe atoms located at the 16i site (space
      group I4/m) of the majority phase and of the minority phase are
      antiferromagnetically ordered, with the Neel temperature T(N) = 518.0(3.6) K. The
      magnetic moments at 5.0 K of 2.09(1) and 2.28(2) MU(B) in these two phases are
      tilted from the crystallographic c axis by 18(1) degrees  and 32(2) degrees ,
      respectively. The Debye temperature of Tl0.53K0.47Fe1.64Se2 is found to be 228(4)
      K.

PMID- 22627155
TI  - Turkish apheresis activity for 2011.

PMID- 22627156
TI  - Approaching stimuli bias attention in numerical space.
AB  - Increasing evidence suggests that common mechanisms underlie the direction of
      attention in physical space and numerical space, along the mental number line.
      The small leftward bias (pseudoneglect) found on paper-and-pencil line bisection
      is also observed when participants 'bisect' number pairs, estimating (without
      calculating) the number midway between two others. Here we investigated the
      effect of stimulus motion on attention in numerical space. A two-frame apparent
      motion paradigm manipulating stimulus size was used to produce the impression
      that pairs of numbers were approaching (size increase from first to second
      frame), receding (size decrease), or not moving (no size change). The magnitude
      of pseudoneglect increased for approaching numbers, even when the final stimulus
      size was held constant. This result is consistent with previous findings that
      pseudoneglect in numerical space (as in physical space) increases as stimuli are
      brought closer to the participant. It also suggests that the perception of
      stimulus motion modulates attention over the mental number line and provides
      further support for a connection between the neural representations of physical
      space and number.

PMID- 22627157
TI  - Lying and executive control: an experimental investigation using ego depletion
      and goal neglect.
AB  - This study investigated whether lying requires executive control using a reaction
      time based lie test. We hypothesized that (1) goal neglect induced by a long
      response-stimulus interval (RSI; 5-8s) would make lying harder relative to a
      short RSI (.2 s) that promoted attentional focus, and (2) participants whose
      executive control resources were depleted by an initial executive control task
      would experience more difficulty to lie than control participants who performed a
      task that required little executive control. Across two experiments, the ego
      depletion manipulation did not reliably affect lying. Both experiments revealed
      that the cognitive cost associated with lying was larger for the long compared to
      the short RSI. This finding supports the idea that lying requires more executive
      control than truth telling. The manipulation of RSI may provide a simple, yet
      effective means to improve lie detection accuracy.

PMID- 22627158
TI  - Extended practice of reciprocal wrist and arm movements of varying difficulties.
AB  - An experiment was designed to determine the degree to which reciprocal aiming
      movements of the wrist and arm with various accuracy requirements (Fitts' tasks)
      are enhanced by extended practice. The vast majority of research on motor
      learning shows performance improvement over practice. However, literature
      examining the effect of practice on Fitts' task performance is limited and
      inconclusive. Participants were asked to flex/extend their limb/lever in the
      horizontal plane at the wrist (arm stabilized) or elbow joint (wrist stabilized)
      in an attempt to move back and forth between two targets as quickly and
      accurately as possible. The targets and current position of the limb were
      projected on the screen in front of the participant. Target width was manipulated
      with amplitude constant (16 degrees ) in order to create indexes of difficulty
      (ID) of 1.5, 3, 4.5, and 6. Contrary to the earlier reports, after 20 days of
      practice, we found minimal changes in movement time or the movement time-ID
      relationships for the arm and wrist over practice. However, the variability in
      the movement endpoints decreased over practice and wrist movements at ID=6 were
      characterized by shorter movement times and longer dwell times relative to arm
      movements with dwell time for the wrist increasing over practice. These data are
      consistent with the notion that Fitts' tasks provide a stable measure of
      perceptual-motor capabilities.

PMID- 22627159
TI  - Constant or variable practice: recreating the especial skill effect.
AB  - An especial skill occurs when performance of a single action from within a class
      of actions produces an advantage in performance. This advantage in a single
      action over others in the class is presumed to result from large amounts of
      practice performing the specific action (Keetch, Schmidt, Lee, & Young, 2005). In
      an experiment involving the learning of a basketball set shot, practice was
      manipulated to identify whether an especial skill effect emerges at the free
      throw line as a result of constant practice conditions in novice performers.
      After a pretest, which involved set shots across five distances, participants
      were randomly assigned to one of two intervention groups. A constant practice
      group (n=10) performed 300 trials of the set shot at the 15 ft free throw line
      only, whereas a variable practice group (n=10) performed 300 trials across five
      distances. Shot accuracy increased for both groups as a result of practice at the
      15' distance. However, on the posttest, a significant difference was reported
      between actual and expected scores for the constant practice group only. This
      finding provided evidence that an effect similar to that seen for especial skills
      emerges as a result of constant practice. Although an especial skill effect could
      result from massive amounts of practice, we show it can emerge as a result of
      short term repetitive practice, indicating that the type, rather than amount, of
      practice is important.

PMID- 22627160
TI  - Short-term storage capacity for visual objects depends on expertise.
AB  - Visual short-term memory (VSTM) has traditionally been thought to have a very
      limited capacity of around 3-4 objects. However, recently several researchers
      have argued that VSTM may be limited in the amount of information retained rather
      than by a specific number of objects. Here we present a study of the effect of
      long-term practice on VSTM capacity. We investigated four age groups ranging from
      pre-school children to adults and measured the change in VSTM capacity for
      letters and pictures. We found a clear increase in VSTM capacity for letters with
      age but not for pictures. Our results indicate that VSTM capacity is dependent on
      the level of expertise for specific types of stimuli.

PMID- 22627161
TI  - Neonatal conductive hearing loss disrupts the development of the Cat-315 epitope
      on perineuronal nets in the rat superior olivary complex.
AB  - The critical period is a postnatal window characterized by a high level of
      experience-dependent neuronal plasticity in the central nervous system and
      sensory deprivation during this period significantly impacts neurological
      function. Perineuronal nets (PNNs) are specialized aggregates of the
      extracellular matrix which ensheath neuronal cell bodies, primary dendrites and
      axon hillocks and function in neuronal protection and stabilize synapses. PNNs
      are generally not present at birth, but reach adult-like patterns by the end of
      the third or fourth postnatal week. Their appearance is believed to mark the
      close of the critical period and sensory deprivation during this epoch disrupts
      development of PNNs. Here we investigate the postnatal development of two PNN
      markers (Wisteria floribunda agglutinin [WFA] and Cat-315) and the effect of
      neonatal conductive hearing loss (CHL) on their development. Our data indicates
      that these PNN markers are not present in the superior olivary complex (SOC) at
      birth, but develop over the first four postnatal weeks in different temporal
      patterns and also that neonatal CHL results in a significant decrease in the
      number of SOC neurons associated with Cat-315 reactive PNNs.

PMID- 22627162
TI  - Effects of a 4 month enriched environment on the hippocampus and the myelinated
      fibers in the hippocampus of middle-aged rats.
AB  - An enriched environment has been shown to enhance learning and memory and to
      induce morphological changes in the hippocampus. In the present study, 14-month
      (middle-aged) female and male Sprague-Dawley rats were randomly divided into
      enriched environment (EE) rats and standard environment (SE) rats. EE rats were
      reared in an enriched environment and SE rats were reared in a standard
      environment for 4 months. The spatial learning capacity was assessed with Morris
      water maze. The hippocampus and the myelinated fibers in the rat hippocampus were
      quantitatively investigated with a transmission electronic microscope technique
      and stereological methods. The female rats housed in an enriched environment
      showed improved performance in the Morris water maze. There was no significant
      difference in the total volume of hippocampus between SE rats and EE rats. The
      total length and total volume of the myelinated fibers in the hippocampus of the
      female and male EE rats were significantly increased, respectively, when compared
      to the female and male SE rats. The increase of the total length of the
      myelinated nerve fibers in the hippocampus was mainly due to the increase of the
      myelinated fibers with diameters from 0.5 to 0.9 MUm. Our results showed that a 4
      month enriched environment had significant effects on the spatial learning
      capacity and the myelinated fibers in the hippocampus of middle-aged rats. The
      present study might provide an important theoretical basis for searching for an
      ethological strategy to delay the progress of brain aging in the future.

PMID- 22627164
TI  - Increased excitability and altered action potential waveform in cerebellar
      granule neurons of the Ts65Dn mouse model of Down syndrome.
AB  - Down syndrome (DS) is characterized by intellectual disability and impaired motor
      control. Lack of coordinated movement, poor balance, and unclear speech imply
      dysfunction of the cerebellum, which is known to be reduced in volume in DS. The
      principal cause of the smaller cerebellum is a diminished number of granule cells
      (GCs). These neurons form the 'input layer' of the cerebellar cortex, where
      sensorimotor information carried by incoming mossy fibers is transformed before
      it is conveyed to Purkinje cells and inhibitory interneurons. However, it is not
      known how processing of this information is affected in the hypogranular
      cerebellum that characterizes DS. Here we explore the possibility that the
      electrical properties of the surviving GCs are changed. We find that in the
      Ts65Dn mouse model of DS, GCs have a higher input resistance at voltages
      approaching the threshold for firing, which causes them to be more excitable. In
      addition, they fire narrower and larger amplitude action potentials. These subtly
      modified electrical properties may result in atypical transfer of information at
      the input layer of the cerebellum.

PMID- 22627163
TI  - Effects of ethanol during adolescence on the number of neurons and glia in the
      medial prefrontal cortex and basolateral amygdala of adult male and female rats.
AB  - Human adolescents often consume alcohol in a binge-like manner at a time when
      changes are occurring within specific brain structures, such as the medial
      prefrontal cortex (mPFC) and the basolateral nucleus of the amygdala (BLN). In
      particular, the number of neurons and glia is changing in both of these areas in
      the rat between adolescence and adulthood (Markham et al., 2007; Rubinow and
      Juraska, 2009). The current study investigated the effects of ethanol exposure
      during adolescence on the number of neurons and glia in the adult mPFC and BLN in
      Long-Evans male and female rats. Saline or 3g/kg ethanol was administered between
      postnatal days (P) 35-45 in a binge-like pattern, with 2days of injections
      followed by 1 day without an injection. Stereological analyses of the ventral
      mPFC (prelimbic and infralimbic areas) and the BLN were performed on brains from
      rats at 100 days of age. Neuron and glia densities were assessed with the optical
      disector and then multiplied by the volume to calculate the total number of
      neurons and glia. In the adult mPFC, ethanol administration during adolescence
      resulted in a decreased number of glia in males, but not females, and had no
      effect on the number of neurons. Adolescent ethanol exposure had no effects on
      glia or neuron number in the BLN. These results suggest that glia cells in the
      prefrontal cortex are particularly sensitive to binge-like exposure to ethanol
      during adolescence in male rats only, potentially due to a decrease in
      proliferation in males or protective mechanisms in females.

PMID- 22627166
TI  - Treatment of depression in first episode of schizophrenia: results from EUFEST.
AB  - Depressive symptomatology is an important target of treatment in first episode
      schizophrenia. This reanalysis of the European First Episode Schizophrenia Trial
      (EUFEST) describes the depressive symptomatology and the effect of antipsychotic
      treatment in patients suffering from first episode schizophrenia and
      schizophreniform disorder randomized to treatment with low dose haloperidol
      (n=103), amisulpride (n=104), olanzapine (n=105), quetiapine (n=104) or
      ziprasidone (n=82) for one year. At baseline, the mean score on the Calgary
      Depression Scale for Schizophrenia (CDSS) was 5.1 (+/-4.9) with 38.3% of patients
      having a CDSS score>=6, i.e. clinically relevant depressive symptom severity.
      During treatment depression scores decreased, the mean CDSS score being 1.1 (+/
      2.1) and 3.0% of patients having a CDSS>=6 at 52 weeks. The proportion of
      patients using antidepressants during the complete trial was 18.5% in the
      haloperidol group, 28.6% in the olanzapine group compared to 5.8% in the
      quetiapine group, 12.5% in the amisulpride group, and 9.8% in the ziprasidone
      group. There were no differences over time in the probability of being depressed
      (CDSS>=6) between the 5 treatment groups after adjustment for antidepressant use,
      nor in a sub analysis of patients who did not take any antidepressant. Depression
      scores at baseline or during the trial had no effect on treatment discontinuation
      or on the reduction of positive symptoms. In summary, the results of EUFEST did
      not demonstrate a differential effect of the antipsychotics studied on depressive
      symptomatology in patients with first episode schizophrenia.

PMID- 22627167
TI  - Combination of polymorphic variants in serotonin transporter and monoamine
      oxidase-A genes may influence the risk for early-onset alcoholism.
AB  - The combinatory effect of polymorphisms in serotonin transporter and monoamine
      oxidase-A genes on the aetiopathogenesis of alcoholism was investigated in a
      sample of 714 individuals. Increased frequency of subjects having three
      'suspected' genotypes (5-HTTLPR-LL, STin2-1010 and MAO-A 3-repeat allele) was
      found among type-2 alcoholic patients (P=0.0189). Results highlight
      serotonergic/genetic contribution to early-onset alcoholism.

PMID- 22627168
TI  - Effect of obesity on serum prostate-specific antigen in Nigerian men.
AB  - OBJECTIVE: Lower serum total prostate-specific antigen (PSA) levels (tPSA) have
      been reported in obese men. It has not been confirmed if this association truly
      exists in all ethnic groups. Thus, we evaluated the relationship between tPSA and
      obesity among Nigerian men. METHODS: Men aged >= 40 years with tPSA <20 ng/ml and
      no known prostatic disease were involved. Obesity was defined using the body mass
      index (BMI) and waist to hip ratio (WHR). Multivariate linear regression was used
      to investigate the relationship between tPSA and either BMI or WHR. The odds of
      having abnormal tPSA were estimated using logistic regression. RESULTS: A total
      of 3,191 men participated, and 3,049 (95.6%) were eligible for analysis. A BMI >=
      25.0 and a WHR >= 0.9 were found in 47.7 and 64.6%, respectively. tPSA was
      significantly associated with age (p < 0.001) and digital rectal examination
      status (p < 0.001). Multivariate linear regression analysis showed no
      relationship between tPSA and obesity (BMI, p = 0.581; WHR, p = 0.160). Adjusting
      for age and digital rectal examination status, logistic regression showed no
      significantly observable trend of having a tPSA level greater than thresholds for
      men with a BMI >= 25 or a WHR >= 0.9 when compared with normal BMI or WHR,
      respectively. CONCLUSION: Although overweight and obesity were common among
      healthy Nigerian men, there was no associated tendency towards lower serum tPSA.

PMID- 22627169
TI  - Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative
      stress by resveratrol in fructose-fed rats.
AB  - Metabolic syndrome and oxidative stress are common complications of type 2
      diabetes mellitus. The present study was designed to determine whether
      resveratrol, a widely used nutritional supplement, can improve insulin
      sensitivity, metabolic complication as well as hepatic oxidative stress in
      fructose-fed rats. Male Sprague Dawley rats (180-200 g) were divided into four
      groups with 8 animals each. Fructose-fed insulin resistant group (Dia) animals
      were fed 65% fructose (Research diet, USA) for a period of 8 weeks, whereas
      control group (Con) animals were fed 65% cornstarch (Research Diet, USA).
      Resveratrol, 10 mg/kg/day (Dia+Resv) or metformin 300 mg/kg/day (Dia+Met) were
      administered orally to the 65% fructose-fed rats for 8 weeks. At the end of the
      feeding schedule, Dia group had insulin resistance along with increased blood
      glucose, triglyceride, uric acid and nitric oxide (NO) levels. Significant
      (p<0.05) increase in hepatic TBARS and conjugated dienes, and significant
      (p<0.05) decrease in hepatic SOD and vitamin C was observed in Dia group compared
      to Con group. Administration of metformin or resveratrol significantly (p<0.05)
      normalized all the altered metabolic parameters. However, a marked insulin
      sensitizing action was only observed in the Dia+Resv group. Similarly, while
      metformin administration failed to normalize the increased TBARS levels and
      decreased SOD activity, resveratrol showed a more promising effect of all
      oxidative stress parameters measured in the present study. Attenuation of hepatic
      oxidative stress in fructose-fed rat liver after resveratrol administration was
      associated with significant (p<0.05) increase in nuclear level of NRF2 compared
      with other groups. The present study demonstrates that resveratrol is more
      effective than metformin in improving insulin sensitivity, and attenuating
      metabolic syndrome and hepatic oxidative stress in fructose-fed rats.

PMID- 22627170
TI  - Endothelium-dependent mechanisms of the vasodilatory effect of the
      endocannabinoid, anandamide, in the rat pulmonary artery.
AB  - Endocannabinoids exhibit vasodilatory properties and reduce blood pressure in
      vivo. However, the influence and mechanism of action of the prominent
      endocannabinoid, anandamide (AEA), in pulmonary arteries are not known. The
      present study determined the vascular response to AEA in isolated rat pulmonary
      arteries. AEA relaxed rat pulmonary arteries that were pre-constricted with U
      46619. This relaxation was reduced by the following conditions:removal of the
      endothelium; in KCl pre-constricted preparations; in the presence of the
      potassium channel (K(Ca)) blockers, tetraethylammonium and the combination of
      charybdotoxin and apamin, and the prostacyclin receptor antagonist, RO1138452.
      Inhibitors of cyclooxygenase (indomethacin), nitric oxide (NO) synthase (N(G)
      nitro-l-arginine methyl ester) and fatty acid amide hydrolase (URB597) alone or
      in combination diminished AEA-induced relaxation in endothelium-intact vessels.
      The remaining experiments were performed in the presence of URB597 to eliminate
      the influence of AEA metabolites. Antagonists of the endothelial cannabinoid
      receptor (CB(x)), O-1918 and cannabidiol, attenuated the AEA-induced response.
      Antagonists of CB(1), CB(2) and TRPV1 receptors, AM251, AM630 and capsazepine,
      respectively, did not modify the AEA-induced response. A reference activator of
      CB(x) receptors, abnormal cannabidiol, mimicked the receptor-mediated AEA
      effects. The present study demonstrated that AEA relaxed rat pulmonary arteries
      in an endothelium-dependent fashion via the activation of the O-1918-sensitive
      CB(x) receptor and/or prostacyclin-like vasoactive products of AEA. One or both
      of these mechanisms may involve K(Ca) or the NO pathway.

PMID- 22627171
TI  - Corticosteroid treatment of pure red cell aplasia in a patient with hepatitis A.
AB  - Secondary pure red cell aplasia (PRCA), as an extrahepatic manifestation of
      hepatitis A virus infection, has been reported on rare occasions. We report
      herein an unusual case of hepatitis A complicated by PRCA. In addition, we
      reviewed nine cases reported in the English literature. Our case of nonfulminant
      hepatitis A complicated by PRCA and hemolytic anemia was successfully treated
      with initial transfusion and corticosteroid therapy for 18 weeks. The patient's
      hematologic abnormalities and liver function tests re-normalized completely. We
      review clinical features and effective therapeutic strategies for this disease
      entity.

PMID- 22627172
TI  - Keep on rolling: optimizing human islet transport conditions using a perfused
      rotary system.
AB  - The setup of an islet isolation facility designed along the rules of good
      manufacturing practice (GMP) is a technically challenging, cost and time
      intensive process. ( 1)  Consequently, several institutions have decided to
      perform transplantation of islets isolated at another center with an already
      standing expertise. Such a solution includes the necessity to transport the
      isolated islets from the isolation to the transplantation facility. In spite of
      its importance, an ideal solution for the transport of the isolated human islets
      has still not been established. Here, we present an islet transport device suited
      to transport human islet cells under reproducible conditions and minimized cell
      stress. The transport simulation of the human islets was performed in a
      transfused "rotary transport system for islets" termed "ROTi." Besides measuring
      standard metabolic (LDH, lactate, glucose) and physical parameters (pH, dissolved
      oxygen and temperature), we used five different live stains in combination with
      real time live confocal microscopy to document islet quality parameters. As live
      stains we added tetramethylrhodamine methyl ester, cell permeant
      acetoxymethylester, propidium iodide, annexin-fitc and fluorescent wheat germ
      agglutinin, and assessed mitochondrial membrane potentials, calcium levels, cell
      death, apoptosis or cell morphology, respectively.   We compared the viability of
      human islets after 24 h incubation in the ROTi device to an incubation simulating
      "standard" shipment of islets in 50 ml tubes. All cell viability parameters
      studied (mitochondrial membrane potentials, calcium content, apoptosis, cell
      death as well as cell morphology) documented a significantly better cell
      viability in the ROTi fraction compared with the simulated "standard" shipment
      fraction. Besides maintaining islet cell viability, the ROTi bears the advantage
      of a better reproducibility of islet transport conditions.

PMID- 22627174
TI  - A DIEP perforator with a twist!

PMID- 22627175
TI  - The amino acid-polyamine-organocation superfamily.
AB  - The amino acid-polyamine-organocation (APC) superfamily has been shown to include
      five recognized families, four of which are specific for amino acids and their
      derivatives. Recent high-resolution X-ray crystallographic data have shown that
      four additional transporter families (BCCT, TC No. 2.A.15; SSS, 2.A.21; NSS,
      2.A.22; and NCS1, 2.A.39), transporting a wide range of solutes, exhibit
      sufficiently similar folds to suggest a common evolutionary origin. We have used
      established statistical methods, based on sequence similarity, to show that these
      families are, in fact, members of the APC superfamily. We also identify two
      additional families (NCS2, 2.A.40; SulP, 2.A.53) as being members of this
      superfamily. Repeat sequences, each having five transmembrane alpha-helical
      segments and arising via ancient intragenic duplications, are demonstrated for
      all of these families, further strengthening the conclusion of homology. The APC
      superfamily appears to be the second largest superfamily of secondary carriers,
      the largest being the major facilitator superfamily (MFS). Although the topology
      of the members of the APC superfamily differs from that of the MFS, both families
      appear to have arisen from a common ancestral 2 TMS hairpin structure that
      underwent intragenic triplication followed by loss of a TMS in the APC family, to
      give the repeat units that are characteristic of these two superfamilies.

PMID- 22627176
TI  - Dietary sodium intake and cardiovascular mortality: controversy resolved?
AB  - Universal reduction in sodium intake has long been recommended, largely because
      of its proven ability to lower blood pressure for some. However, multiple
      randomized trials have also demonstrated that similar reductions in sodium
      increase plasma renin activity and aldosterone secretion, insulin resistance,
      sympathetic nerve activity, serum cholesterol, and triglyceride levels. Thus, the
      health consequences of reducing sodium cannot be predicted by its impact on any
      single physiologic characteristic but will reflect the net of conflicting
      effects. Some 23 observational studies (>360,000 subjects and >26,000 end points)
      linking sodium intake to cardiovascular outcomes have yielded conflicting
      results. In subjects with average sodium intakes of less than 4.5 g/day, most
      have found an inverse association of intake with outcome; in subjects with
      average intakes greater than 4.5 g/day, most reported direct associations.
      Finally, in two, a "J-shaped" relation was detected. In addition, three
      randomized trials have found that heart failure subjects allocated to 1.8 g of
      sodium have significantly increased morbidity and mortality compared with those
      at 2.8 g. At the same time, a randomized study in retired Taiwanese men found
      that allocation to an average intake of 3.8 g improved survival compared with 5.3
      g. Taken together, these data provide strong support for a "J-shaped" relation of
      sodium to cardiovascular outcomes. Sodium intakes above and below the range of
      2.5-6.0 g/day are associated with increased cardiovascular risk. This robust body
      of evidence does not support universal reduction of sodium intake.

PMID- 22627177
TI  - Isocyanate and VOC exposure analysis using Flexane(r).
AB  - Flexane(r) 80 is a trowelable urethane product used in combination with cleaners
      and primers to effect rubber conveyor belt repairs. These products are of concern
      due to the potential for worker exposure to isocyanates and volatile organic
      compounds (VOCs). Small chamber experiments were used to identify chemicals
      liberated to the ambient air from each of the Flexane(r)-related products. A new
      sample collection method using treated cotton sleeves as a surrogate skin surface
      to assess potential dermal exposure to isocyanates during mixing and application
      of the Flexane(r) product was validated. Six simulations of a worst case scenario
      were performed by an experienced belt repair technician in a walk-in laboratory
      exposure chamber. Analysis of air samples from the large chamber simulations did
      not detect airborne isocyanates. The average airborne VOC concentrations were
      below established occupational exposure levels. Dermal sleeve samples detected
      intermittent and low levels of isocyanates from self-application while wearing
      gloves having surface residues of uncured Flexane(r). The data strongly suggest
      that the normal and intended use of Flexane(r) putty, and its associated products
      under worst case or typical working conditions is not likely to result in worker
      VOC or isocyanate exposure levels sufficient to produce adverse health effects.

PMID- 22627178
TI  - Aye-aye (Daubentonia madagascariensis) feeding strategies at Ranomafana National
      Park, Madagascar: an indirect sampling method.
AB  - In this research, we focused on aye-aye populations in Ranomafana National Park,
      Madagascar. From August to December 2008, we tested how aye-aye feeding was
      influenced by presence/absence of both fruiting and non-fruiting Canarium trees.
      Deadwood feeding traces were used as a proxy for evidence of Canarium feeding. We
      enumerated deadwood feeding traces in 20 locations, 10 with Canarium, 10 without.
      Each location contained two transects (80 m L * 20 m W) for a total area of 5.6
      ha. Feeding trace results for Canarium locations compared to non-Canarium
      locations were not significant (Z = -1.926, p = 0.083); however, feeding trace
      results were significant when comparing fruiting and non-fruiting Canarium
      locations (Z = -2.417, p = 0.016). These results highlight the importance of
      Canarium in the diet of aye-ayes and demonstrate how the distribution of this
      resource may influence the foraging behavior of aye-ayes.

PMID- 22627179
TI  - APOE: a risk factor for multiple disorders.

PMID- 22627181
TI  - X-ray linear dichroism dependence on ferroelectric polarization.
AB  - X-ray absorption spectroscopy and photoemission electron microscopy are
      techniques commonly used to determine the magnetic properties of thin films,
      crystals, and heterostructures. Recently, these methods have been used in the
      study of magnetoelectrics and multiferroics. The analysis of such materials has
      been compromised by the presence of multiple order parameters and the lack of
      information on how to separate these coupled properties. In this work, we shed
      light on the manifestation of dichroism from ferroelectric polarization and
      atomic structure using photoemission electron microscopy and x-ray absorption
      spectroscopy. Linear dichroism arising from the ferroelectric order in the
      PbZr0:2Ti0:8O3 thin films was studied as a function of incident x-ray
      polarization and geometry to unambiguously determine the angular dependence of
      the ferroelectric contribution to the dichroism. These measurements allow us to
      examine the contribution of surface charges and ferroelectric polarization as
      potential mechanisms for linear dichroism. The x-ray linear dichroism from
      ferroelectric order revealed an angular dependence based on the angle between the
      ferroelectric polarization direction and the x-ray polarization axis, allowing a
      formula for linear dichroism in ferroelectric samples to be defined.

PMID- 22627180
TI  - Pesticide exposure and Parkinson's disease: epidemiological evidence of
      association.
AB  - It has been suggested that exposure to pesticides might be involved in the
      etiology of Parkinson's disease (PD). We conducted an updated systematic review
      of the epidemiologic literature over the past decade on the relationship between
      pesticide exposure and PD, using the MEDLINE database. Despite methodological
      differences, a significantly increased PD risk was observed in 13 out of 23 case
      control studies that considered overall exposure to pesticides (risk estimates of
      1.1-2.4) and in 10 out of 12 studies using other research designs (risk estimates
      of 2 or higher). Various studies found stronger associations in genetically
      susceptible individuals. Among a growing number of studies on the effects of
      exposure to specific pesticides (n=20), an increased PD risk has been associated
      with insecticides, especially chlorpyrifos and organochlorines, in six studies
      (odds ratios of 1.8-4.4), and with the herbicide paraquat, the fungicide maneb or
      the combination of both. Findings considerably strengthen the evidence that
      exposure to pesticides in well water may contribute to PD, whereas studies of
      farming and rural residence found inconsistent or little association with the
      disease. Taken together, this comprehensive set of results suggests that the
      hypothesis of an association between pesticide exposure and PD cannot be ruled
      out. However, inadequate data on consistent responses to exposure hinder the
      establishment of a causal relationship with PD. Given the extensive worldwide use
      of many pesticides, further studies are warranted in larger populations that
      include detailed quantitative data on exposure and determination of genetic
      polymorphisms.

PMID- 22627182
TI  - Effects of steady-state lopinavir/ritonavir on the pharmacokinetics of
      pitavastatin in healthy adult volunteers.
AB  - OBJECTIVES: Pitavastatin, a statin recently approved in the United States, has a
      potential benefit of reduced risk of cytochrome P450 (CYP)-mediated drug-drug
      interaction due to minimal metabolism by the CYP system. The primary objective
      was to investigate pharmacokinetic (PK) effects of lopinavir/ritonavir 400 mg/100
      mg twice daily on pitavastatin 4 mg when coadministered. DESIGN: This was an open
      label one-arm study. METHOD: Pitavastatin 4 mg was administered once daily (days
      1-5 and days 20-24). Lopinavir/ritonavir 400 mg/100 mg was administered twice
      daily (days 9-24). Plasma samples for PK assessments were collected on days 5,
      19, and 24. Plasma concentrations of analytes were determined by liquid
      chromatography with tandem mass spectrometric detection methods. RESULTS: PK data
      were available for 23 of 24 subjects enrolled. For pitavastatin, area under the
      concentration time curve (AUC0-tau) and maximum concentration (C(max)) were 136.8
      +/- 52.9 ng.h(-1).mL(-1) and 58.6 +/- 30.4 ng/mL, respectively, when given alone,
      versus 113.9 +/- 53.8 ng.h(-1).mL(-1) and 58.2 +/- 32.7 ng/mL when combined with
      lopinavir/ritonavir. The geometric mean ratio for AUC(0-tau) for pitavastatin
      with lopinavir/ritonavir versus pitavastatin alone was 80.0 (90% confidence
      interval: 73.4 to 87.3) and C(max) was 96.1 (90% confidence interval: 83.6 to
      110.4). Median T(max) of pitavastatin was approximately 0.5 hours for both
      treatments. The PK effect of pitavastatin on lopinavir/ritonavir was minimal. No
      significant safety issues were reported. CONCLUSIONS: The effect on exposures
      when pitavastatin and lopinavir/ritonavir are coadministered was minimal.
      Concomitant use of pitavastatin and lopinavir/ritonavir was safe and well
      tolerated in healthy adult volunteers.

PMID- 22627183
TI  - Greater HIV testing after Veterans Health Administration policy change: the
      experience from a VA Medical Center in a high HIV prevalence area.
AB  - Veterans Health Administration changed its HIV testing policy to remove
      requirements for written informed consent with pretest/posttest counseling and to
      make testing part of routine care in August 2009. HIV testing percentages were
      compared for 1-year periods before and after this change at our medical center
      located in Washington, DC, the city with the highest US HIV prevalence. After
      this policy change, HIV screening rose from 5.5% to 10.3% of persons in care with
      the majority of testing in outpatient settings and the greatest increase among
      veterans aged 61-70. Broadening of HIV testing has significance for HIV detection
      and prevention.

PMID- 22627184
TI  - Undiagnosed tuberculosis among HIV clinic attendees: association with
      antiretroviral therapy and implications for intensified case finding, isoniazid
      preventive therapy, and infection control.
AB  - OBJECTIVES: Initiation of antiretroviral therapy (ART) and the 3I's are
      strategies to prevent HIV-associated tuberculosis (TB). We describe factors
      associated with undiagnosed TB among HIV-infected patients attending an HIV
      clinic in South Africa and discuss implications for the 3 Is. DESIGN: Convenience
      sample of HIV clinic attendees. METHODS: HIV-infected participants were assessed
      for TB using a symptom screen, sputum-smear microscopy, sputum and blood
      mycobacterial culture, fine needle aspiration of enlarged lymph nodes, and chest
      radiography. RESULTS: Four hundred twenty-two participants were enrolled. The
      median age and CD4+ T-cell count were 37 years [interquartile range (IQR): 31-44
      years] and 215 cells per microliter (IQR: 107-347 cells/MUL). Forty-seven percent
      had been on ART for a median duration of 8 months (IQR: 3.3-22.8 months). Three
      hundred sixty-one participants (85.6%) reported TB symptoms. Twenty-seven
      participants (6.4%) met criteria for bacteriologically confirmed TB and 50
      (11.6%) for any form of TB. Bacteriologically confirmed TB was associated with
      CD4+ T-cell counts <=100 cells per microliter (odds ratio: 5.05, 95% confidence
      interval: 1.69 to 15.12) when compared with CD4+ T-cell counts >200 cells per
      microliter and hemoglobin {hemoglobin < 10 g/dL [odds ratio 3.12 (95% confidence
      interval: 1.26 to 7.72)]}. CONCLUSIONS: Undiagnosed TB among HIV-infected
      ambulatory patients was associated with low CD4+ T-cell counts regardless of ART
      status. TB screening algorithms which include CD4+ T-cell count and hemoglobin
      testing may be an effective way to identify HIV-infected clinic attendees at
      highest risk of undiagnosed TB. Isoniazid preventive therapy and TB infection
      control are essential for reducing occurrence of HIV-associated TB even after ART
      initiation.

PMID- 22627185
TI  - Impaired performance of female APP/PS1 mice in the Morris water maze is coupled
      with increased Abeta accumulation and microglial activation.
AB  - BACKGROUND: Alzheimer's disease (AD) is characterized by progressive neuronal
      loss and cognitive decline. Epidemiological studies suggest that the risk of AD
      is higher in women even when data are adjusted for age. OBJECTIVE: We set out to
      compare changes in 9-month-old male and female mice which overexpress amyloid
      precursor protein (APP) with presenilin (PS1; APP/PS1 mice) and to evaluate
      whether any changes were coupled with deficits in spatial learning. METHODS:
      APP/PS1 mice were assessed for their ability to learn in the Morris water maze
      and Abeta burden assessed by Congo Red and Abeta triple ultrasensitive assay.
      Neuroinflammatory changes were examined in brain tissue along with expression of
      Abeta-generating and Abeta-degrading enzymes. RESULTS: A deficit in reversal
      phase learning in the Morris water maze was observed in female mice and was
      paralleled by evidence of increased accumulation of Abeta, microglial activation
      and expression of IL-1beta. Accumulation of Abeta was coupled with an increase in
      expression of BACE-1 and a decrease in insulin-degrading enzyme (IDE).
      CONCLUSION: The results indicate that the observed impairment in spatial memory
      in female APP/PS1 mice correlated with increased Abeta burden and the changes in
      Abeta may have occurred as a result of enhanced BACE-1 and decreased IDE
      expression.

PMID- 22627186
TI  - Hyperglycemia in the newborn--clinical guidelines are needed but must be based on
      correct reporting of the data.

PMID- 22627187
TI  - Occult functioning vagal paraganglioma in the infrahyoid carotid sheath.
AB  - Paragangliomas are highly vascular tumors that arise from chief cells in extra
      adrenal paraganglia of the autonomic nervous system. Vagal paragangliomas occur
      along the vagal nerve, usually located in the rostral portion of the vagus nerve
      in the vicinity of the gangliom nodosum. Actively functional vagal paragangliomas
      are rare. We report a patient with functioning vagal paraganglioma located in the
      infrahyoid carotid sheath. The patient had no history of hypertension and
      catecholamines were not measured before surgery. The findings of diagnostic
      imaging workup, including computed tomography, ultrasonography and magnetic
      resonance, were suggestive of paraganglioma. The blood pressure and pulse rates
      increased sharply intraoperatively during tumor manipulation, together with
      spikes in noradrenaline and dopamine. The tumor was removed with successful
      preservation of the vagus nerve trunk. The blood catecholamine levels returned to
      normal immediately after surgery. Head and neck surgeons should be aware of
      occult functioning paragangliomas and patients with such tumors should undergo
      full hormonal assessment.

PMID- 22627188
TI  - TGF-beta-induced epithelial-mesenchymal transition: a link between cancer and
      inflammation.
AB  - Metastatic spread of tumor cells to vital organs is the major cause of death in
      cancer. Accumulating data support an important role of infiltrating immune cells
      in promoting carcinoma progression into metastatic disease. Tumor-infiltrating
      immune cells produce and secrete cytokines, growth factors and proteases that re
      activate latent developmental processes including epithelial-mesenchymal
      transition (EMT). EMT provides tumor cells with invasive, migratory and stem cell
      properties allowing them to disseminate and propagate at distant sites. Induction
      of EMT requires two criteria to be fulfilled: (i) cells are competent to undergo
      EMT (ii) an EMT-permissive microenvironment exists. The cytokine TGF-beta, which
      is expressed by tumor-infiltrating immune cells, stands out as a master regulator
      of the pro-invasive tumor microenvironment. TGF-beta cooperates with stem cell
      pathways, such as Wnt and Ras signaling, to induce EMT. In addition, TGF-beta
      contributes to an EMT-permissive microenvironment by switching the phenotypes of
      tumor-infiltrating immune cells, which thereby mount pro-invasive and pro
      metastatic immune responses. In this review, we discuss the role of TGF-beta
      induced EMT as a link between cancer and inflammation in the context of
      questions, which from our point of view are key to answer in order to understand
      the functionality of EMT in tumors.

PMID- 22627193
TI  - Regulatory T cells are decreased in acute RHDV lethal infection of adult rabbits.
AB  - Rabbit hemorrhagic disease virus (RHDV) is the etiologic agent of rabbit
      hemorrhagic disease (RHD), an acute lethal infection that kills 90% of adult
      rabbits due to severe acute liver inflammation. Interestingly, young rabbits are
      naturally resistant to RHDV infection. Here, we have compared naturally occurring
      CD4(+)Foxp3(+) regulatory T cells (Tregs) between young and adult rabbits after
      infection by RHDV. The number and frequency of Tregs was decreased in the spleen
      of adult rabbits 24h after the RHDV infection; this was in contrast with the
      unchanged number and frequency of splenic Tregs found in young rabbits after the
      same infection. Also, serum levels of IL-10 and TGF-beta were enhanced in the
      infected adult rabbits whereas no alteration was observed in infected young
      rabbits. However, this increase is accompanied by a burst of pro-inflammatory
      cytokines, but seems not able to prevent the death of the animals with severe
      acute liver inflammation in few days after infection. Since Tregs downregulate
      inflammation, we conclude that their decrease may contribute to the natural
      susceptibility of adult rabbits to RHDV infection.

PMID- 22627194
TI  - Effects of fructooligosaccharide-inulin on Salmonella-killing and inflammatory
      gene expression in chicken macrophages.
AB  - Salmonella Enteritidis (SE) is one of the leading causes of food-borne
      salmonellosis, and macrophages play an essential role in eliminating this
      pathogen. Among the interventions to improve Salmonella clearance in chickens are
      the use of prebiotics and direct fed microbials (DFM) in animal feed as they have
      immunomodulatory effects. Therefore, we tested the influence of a prebiotic
      fructooligosaccharide (FOS)-inulin on the ability of the chicken macrophage HD11
      cell line to phagocytose and kill SE, and express selected inflammatory cytokines
      and chemokines in an in vitro model. There were significantly fewer viable
      intracellular SE in HD11 cells treated with FOS-inulin than the untreated cells.
      However, SE phagocytosis, nitric oxide expression or production were not
      influenced by the prebiotic treatment. Among the inflammatory markers tested, IL
      1beta expression was significantly lower in HD11 cells treated with FOS-inulin.
      These results suggest that FOS-inulin has the ability to modulate the innate
      immune system as shown by the enhanced killing of SE and decreased inflammasome
      activation.

PMID- 22627195
TI  - LC3 as a potential therapeutic target in hypoxia-induced pulmonary hypertension.
AB  - Recent research suggests that microtubule-associated protein 1 light chain 3B
      (LC3B) confers protection against hypoxia-induced pulmonary hypertension (HPH) by
      inhibiting proliferation of pulmonary artery (PA) wall cells. We recently
      demonstrated that 17beta-estradiol (E2), a sex hormone with known protective
      properties in HPH, increases lung LC3-II expression in chronically hypoxic male
      Sprague-Dawley rats. Stimulatory E2 effects on LC3-II were recapitulated in
      isolated hypoxic (1% O 2 for 48 h), but not room air-exposed primary rat PA
      endothelial cells (PAECs), and were accompanied by hypoxia-specific inhibitory
      effects on other parameters involved in proproliferative signaling (MAPK3/ERK1
      MAPK1/ERK2 activation, VEGF secretion), as well as inhibitory effects on PAEC
      proliferation. Taken together, these results suggest that E2 mediates hypoxia
      specific antiproliferative effects in PAECs, and that stimulation of autophagy
      may be one of the underlying mechanisms of E2-mediated protection in HPH. Viewed
      in the context of previously published data, these results indicate that LC3 1)
      exerts protective effects in the pathogenesis of HPH, and 2) may represent a
      potential target for future therapeutic interventions in HPH.

PMID- 22627196
TI  - Uliginosin B presents antinociceptive effect mediated by dopaminergic and opioid
      systems in mice.
AB  - Previous studies have shown that uliginosin B inhibits dopamine reuptake in rat
      brain. This compound occurs in Hypericum polyanthemum and H. caprifoliatum for
      which was reported to have antinociceptive effect sensitive to naloxone. The aim
      of this study was to assess the antinociceptive effect of uliginosin B and to
      evaluate the involvement of opioid and dopaminergic receptors activation.
      Uliginosin B presented antinociceptive effect in hot-plate and abdominal writhing
      tests, in mice, at doses that did not impair the motor coordination (15 mg/kg,
      i.p.). Uliginosin B in high dose (90 mg/kg, i.p.) presented ataxic effect in the
      rotarod apparatus. These effects seem to be mediated by distinct receptors since
      the effect on the hot-plate was completely abolished by naloxone and sulpiride,
      but it was unaffected by SCH 23390. On the other hand, the motor impairment
      induced by uliginosin B was completely prevented by naloxone and partially
      prevented by sulpiride and SCH 23390. However, the receptors' activation appears
      to be indirect since uliginosin B did not bind to opioid and dopaminergic
      receptors. Thus, uliginosin B effects probably are due to its ability to inhibit
      monoamine reuptake with consequent activation of dopamine receptors and indirect
      stimulation of opioid system.

PMID- 22627197
TI  - Ziprasidone attenuates brain injury after focal cerebral ischemia induced by
      middle cerebral artery occlusion in rats.
AB  - Ziprasidone is an atypical antipsychotic drug used for the treatment of
      schizophrenia. Recent studies have reported that atypical antipsychotics have
      neuroprotective effects against brain injury. In the present study, the effect of
      ziprasidone on ischemic brain injury was investigated. Focal cerebral ischemia
      was induced by middle cerebral artery occlusion (MCAO) in rats. All the animals
      experienced ischemia for 1h and then underwent reperfusion. The infarct size
      induced by MCAO was significantly reduced in the animals that received acute
      treatment with 5mg/kg ziprasidone and subchronic treatment with 2.5mg/kg
      ziprasidone for 7 days compared with that in the vehicle-treated animals. The
      acute treatment with ziprasidone significantly improved neurological functions,
      as measured by the modified neurological severity score, in a dose-dependent
      manner. The subchronic treatment produced more rapid recovery from functional
      deficits than the vehicle treatment. The immunohistochemical investigation
      revealed that the subchronic treatment prevented severe loss of neuronal marker
      intensity and attenuated the increased in microglial marker intensity in the
      infarcted cortical area. These results suggest that ziprasidone has
      neuroprotective effects in a rat model of ischemic stroke and provide new insight
      for its clinical applications.

PMID- 22627198
TI  - [How to deal with those low parathyroid hormone values in dialysis patients?].
AB  - BACKGROUND: The target for serum parathyroid (PTH) hormone level in dialysis
      patients is higher than that in the normal population in order to prevent
      adynamic bone disease (ABD) that is associated with more frequent cardiovascular
      and bone disease. Based on biological and clinical data, we aimed at identifying
      the different types of low PTH (L-PTH) in order to determine the best therapeutic
      strategies in these patients. METHODS: Between 2004 and 2010, all haemodialysis
      (HD) patients were assessed. Patients with serum L-PTH (<130pg/mL) were
      classified into five groups as follows : 'PTX' for patients with a history of
      parathyroidectomy (PTX); 'HypoMed' for patients with a tendency to hypocalcemia
      without PTX; 'IatroMed' for patients who had undergone excessive PTH-lowering
      treatments (calcium, vitamin D, or cinacalcet); 'EndoG' for patients with
      endogenous hypercalcaemia (immobilization, cancer, or granulomatosis); and
      'SponT' for patients with L-PTH without evident causes and with 'normal' biology
      in most cases. RESULTS: From 520 charts, 163 (31.3 %) L-PTH cases were recorded,
      with 17.7% of PTX in younger patients with longer dialysis times; 2.4% of HypoMed
      in older women with high co-morbidities (these two groups needed calcium and
      vitamin D therapy to prevent hypocalcaemia); 22.6% of IatroMed in diabetic
      patients receiving excessive PTH-lowering treatments; 3% of EndoG in
      hypercalcaemic patients, more frequently in the hospitalization ward; and 54% of
      SponT, more frequently comprising old diabetic patients not receiving PTH
      lowering treatment and without biological signs of ABD. Treatment changes were
      necessary only in cases of IatroMed and EndoG, requiring a lowered prescription
      of PTH-lowering therapies and the addition of bisphosphonates for EndoG.
      CONCLUSION: In our HD population, we could identify five types of L-PTH based on
      medical conditions and biological data. Only two types, i.e. approximately 25% of
      patients needed therapeutic modifications. For the other patients, L-PTH could be
      maintained without decreasing the calcium and vitamin D intake that can lead to
      osteomalacia or administering recombinant PTH 1-34 or calcium-receptor inhibitors
      that need to be assessed in HD patients.

PMID- 22627199
TI  - Soluble C-X-C chemokine ligand 16 levels are increased in gout patients.
AB  - OBJECTIVES: Soluble C-X-C chemokine ligand 16 (CXCL16) was shown to recruit
      polymorphonuclear cells into synovial tissue in gout patients. The aim of this
      study was to explore the pathophysiological characteristics of CXCL16 in gout
      patients with or without chronic kidney disease (CKD). DESIGN AND METHODS: 42
      gout patients, 22 CKD and 20 healthy subjects were enrolled. Plasma CXCL16 and
      other biochemical parameters were tested. RESULTS: Plasma CXCL16 levels in gout
      subjects with CKD were significantly increased compared with healthy, CKD and
      gout subjects without CKD. Soluble CXCL16 levels in gout subjects were closely
      correlated with renal function and lipid profiles, and independently associated
      with 24h proteinuria, creatinine clearance rate and C-reactive protein.
      CONCLUSION: Our data indicated that plasma CXCL16 levels are significantly
      increased in gout patients with and without CKD, and are independently associated
      with renal function. Elucidating the pathophysiologcial role of CXCL16 in gout
      patients requires further study.

PMID- 22627200
TI  - Development of an immunoassay for differentiating human immunodeficiency virus
      infections--from vaccine-induced immune response in Tiantan vaccine trials in
      China.
AB  - OBJECTIVE: To develop a Rapid Flow-through assay for distinguishing replicating
      Tiantan vaccine-generated serological response from true HIV infection. DESIGN
      AND METHOD: A Rapid Flow-through Test including gp41, gp36, sk1, sk2 and sk3
      antigens was established and the performance of the assay was evaluated in
      clinical studies and compared with ELISA assay. RESULTS: Sk1, sk2 and sk3
      peptides performed at 100% specificity and slightly but not significantly
      different sensitivities between ELISA assay (92%, 76% and 41%) and Flow-through
      Test Kit (92%, 75% and 40%) in diagnosing HIV-1 infections. Of particular
      importance, Tiantan vaccine recipients that gave false-positive results in gp41
      serodetection scored negative for sk1, sk2 and sk3 antibodies. CONCLUSION: The
      Rapid Flow-through Test could be a robust tool in both diagnosing HIV-1/2
      infections and differentiating between vaccines induced immunity and immunity
      resulting from natural exposure, thus serving as potential implementation in HIV
      vaccine trials.

PMID- 22627201
TI  - Cathepsin D activity in nasal polyps.
AB  - OBJECTIVES: The aim of the study was to assess the activity of cathepsin D in
      polyps removed during first-time FESS surgery and in recurrent polyps removed
      during successive FESS surgeries. DESIGN AND METHODS: The study examined 24
      polyps: 11 polyps were removed during first-time surgical procedures (termed
      primary polyps in the study), and 13 recurrent polyps were removed in successive
      FESS surgeries (termed polyps after re-polypectomy in the study). The activity of
      cathepsin D was determined by measuring the tyrosine released from denatured
      hemoglobin. RESULT: The average cathepsin D activity in polyps after re
      polypectomy was 74% higher than the average activity in primary polyps, whereas
      the difference between the maximum and the minimum cathepsin D activities in
      polyps after re-polypectomy was twofold greater than the respective difference in
      primary polyps. CONCLUSION: Differences in cathepsin activity and the protein
      content, likely to be significant in the process of polyp recurrence, were
      observed in both groups of polyps.

PMID- 22627202
TI  - Spin dynamics of the S = 5/2 2D triangular antiferromagnet Ba3NbFe3Si2O14.
AB  - We report pulse-field magnetization, ac susceptibility, and 100 GHz electron spin
      resonance (ESR) measurements on the S = 5/2 two-dimensional triangular compound
      Ba3NbFe3Si2O14 with the Neel temperature T(N) = 26 K. The magnetization curve
      shows an almost linear increase up to 60 T with no indication of a one-third
      magnetization plateau. An unusually large frequency dependence of the ac
      susceptibility in the temperature range of T = 20-100 K reveals a spin-glass
      behavior or superparamagnetism, signaling the presence of frustration-related
      slow magnetic fluctuations. The temperature dependence of the ESR linewidth
      exhibits two distinct critical regimes; (i) DeltaH(pp)(T) is proportional to (T
      T(N))(-p) with the exponent p = 0.2(1)-0.2(3) for temperatures above 27 K, and
      (ii) DeltaH(pp)(T) is proportional to (T-T*)(-p) with T* = 12 K and p = 0.8(1)
      0.8(4) for temperatures between 12 and 27 K. This is interpreted as indicating a
      dimensional crossover of magnetic interactions and the persistence of short-range
      correlations with a helically ordered state.

PMID- 22627203
TI  - Palladium-catalyzed carbocyclization-cross-coupling reactions of two different
      allenic moieties: synthesis of 3-(buta-1,3-dienyl) carbazoles and mechanistic
      insights.
AB  - A palladium-catalyzed chemo-, regio- and stereoselective carbocyclization-cross
      coupling sequence of two different alpha-allenols to afford 3-(E-buta-1,3-dienyl)
      carbazoles is reported.

PMID- 22627204
TI  - Does D put the dilemma in CPD?

PMID- 22627205
TI  - Automaton behaviour.

PMID- 22627207
TI  - Resigned to pension logic.

PMID- 22627206
TI  - DCP LDS.

PMID- 22627209
TI  - Potentially disastrous.

PMID- 22627208
TI  - Managing aspiration.

PMID- 22627210
TI  - A shot in the dark.

PMID- 22627216
TI  - Research trial to improve oral health of children in Northern Ireland.

PMID- 22627221
TI  - Hindsight isn't always 20/20.

PMID- 22627222
TI  - Three cases of oral syphilis - an overview.
AB  - Syphilis is an infectious disease caused by the organism Treponema pallidum.
      There has been a dramatic increase in the number of new cases of syphilis in the
      UK over the past decade. Intra-oral ulceration is often the only presenting
      feature of the disease, which then enters a latent period. A missed diagnosis can
      often lead to serious complications and may result in further spread of the
      disease. Three cases are discussed in this paper with varying clinical
      presentations of the disease. Such a significant increase of syphilis and its
      high infectivity require the dental profession to increase their awareness of
      sexually infectious diseases and the appropriate dental management.

PMID- 22627223
TI  - Antibiotics and oral contraceptives: new considerations for dental practice.
AB  - The aim of this paper is to highlight a change in guidance relating to possible
      interactions between antibiotics and oral contraceptives. Until recently,
      dentists have been advised to warn women taking the combined oral contraceptive
      pill of the routine need to use additional contraceptive measures while taking
      courses of broad spectrum antibiotics. Recent guidance relating to this issue has
      changed and dentists may not be aware of this. This paper reminds dentists of the
      previous guidelines and related evidence, reviews the pharmacokinetics of
      hormonal contraception and presents them with the latest evidence-based guidance.
      This should change their clinical practice.

PMID- 22627225
TI  - Amelogenesis imperfecta: the orthodontic perspective.
AB  - Orthodontics in patients with amelogenesis imperfecta can be complicated by
      commonly occurring dental features in this group as well as patient factors. In
      this article we examine ways to avoid the common pitfalls of orthodontic
      management and the importance of adequate and timely liaison between the general
      dental practitioner and the multidisciplinary team.

PMID- 22627230
TI  - Summary of: the impact of fluoride application training: survey of trained dental
      nurses from King's College Hospital NHS Trust.
AB  - OBJECTIVES: To explore the perceived benefits of a fluoride varnish training
      scheme, subsequent use of extended skills and any barriers that exist, in order
      to inform future training and practice. METHOD: Questionnaire survey of the first
      four cohorts of fluoride varnish training at one London dental hospital. RESULTS:
      Thirty-six (62%) nurses responded to the survey, 89% of whom were using fluoride
      varnishing. 'Personal development', 'NHS initiatives' and 'having a supportive
      principal' were key drivers for course attendance. Over 2,500 fluoride
      application treatments were carried out (range = 0-630) with six nurses providing
      71% of the treatments. Twenty nurses (56%) worked in the salaried primary dental
      care service and provided 69% of treatments, the remaining 31% of treatments were
      provided by the 44% (n = 16) of nurses in general dental practice. Barriers were
      'systems-related' and 'professional', including lack of community programmes,
      consultant oversight, referrals, materials and concerns regarding insurance and
      consent. The majority felt that the course contributed to their professional
      career (97%), and expressed their confidence in conducting fluoride application
      (80%). CONCLUSION: The findings highlight the potential for using extended roles
      to deliver evidence-based prevention and variation in their use; however, there
      is some evidence that organisational and professional barriers exist.

PMID- 22627231
TI  - Summary of: availability of manufacturers' information on efficacy and
      compatibility of detergents used for cleaning dental instruments.
AB  - AIM: To review physico-chemical data supplied for commercially available
      detergents marketed for manual and/or ultrasonic cleansing of reusable dental
      instruments. METHOD: Manufacturers/suppliers of commercially available detergents
      for manual or ultrasonic cleaning of dental instruments within primary dental
      care were invited to supply product information. A structured questionnaire
      requested details on a range of physical and chemical properties for each
      detergent. RESULTS: Seventeen detergent manufacturers/suppliers, encompassing 31
      commercially available detergents were identified. Ten of the 17 manufacturers
      provided information on 23 (74%) of the detergent formulations. Nine detergents
      were of neutral pH, ten mild alkalis (pH 7.5-10.5) and four strong alkalis (pH
      >10.5). Sixteen detergents were recommended for ultrasonic and manual cleaning,
      four stated ultrasonic use and three manual only. Ten detergents cited enzymatic
      activity as their main mode of action, but only six manufacturers provided
      detailed information. Four detergents recommended by manufacturers as suitable
      for manual washing had a strong alkaline pH (>10.5), presenting chemical hazards
      to users. Two strong alkaline detergents did not warn users of potential adverse
      effects of such alkaline solutions (corrosion) upon aluminium containing
      instruments. Only one detergent had investigated the potential toxicity of
      detergent residuals remaining on instruments after reprocessing. CONCLUSION: It
      has proven challenging to collate physico-chemical data on detergents suitable
      for use in manual and/or ultrasonic cleaning of dental instruments in general
      dental practice. Standardisation of information on the nature and efficacy of
      dental detergents in a readily accessible form would be beneficial to dental
      practice.

PMID- 22627232
TI  - Update of guidelines for surgical endodontics - the position after ten years.
AB  - This is the first of a series of articles, which will summarise new or updated
      clinical guidelines produced by the Clinical Standards Committee of the Faculty
      of Dental Surgery, Royal College of Surgeons of England (FDSRCS). Important
      developments for the dental profession from a number of clinical guidelines will
      be presented, commencing with the Guidelines for surgical endodontics. The impact
      of recent evidence relating to the outcome of surgical endodontics and techniques
      such as cone beam computed tomography and microsurgical techniques are
      considered.

PMID- 22627253
TI  - The impact of fluoride application training: survey of trained dental nurses from
      King's College Hospital NHS Trust.
AB  - OBJECTIVES: To explore the perceived benefits of a fluoride varnish training
      scheme, subsequent use of extended skills and any barriers that exist, in order
      to inform future training and practice. METHOD: Questionnaire survey of the first
      four cohorts of fluoride varnish training at one London dental hospital. RESULTS:
      Thirty-six (62%) nurses responded to the survey, 89% of whom were using fluoride
      varnishing. 'Personal development', 'NHS initiatives' and 'having a supportive
      principal' were key drivers for course attendance. Over 2,500 fluoride
      application treatments were carried out (range = 0-630) with six nurses providing
      71% of the treatments. Twenty nurses (56%) worked in the salaried primary dental
      care service and provided 69% of treatments, the remaining 31% of treatments were
      provided by the 44% (n = 16) of nurses in general dental practice. Barriers were
      'systems-related' and 'professional', including lack of community programmes,
      consultant oversight, referrals, materials and concerns regarding insurance and
      consent. The majority felt that the course contributed to their professional
      career (97%), and expressed their confidence in conducting fluoride application
      (80%). CONCLUSION: The findings highlight the potential for using extended roles
      to deliver evidence-based prevention and variation in their use; however, there
      is some evidence that organisational and professional barriers exist.

PMID- 22627254
TI  - Availability of manufacturers' information on efficacy and compatibility of
      detergents used for cleaning dental instruments.
AB  - AIM: To review physico-chemical data supplied for commercially available
      detergents marketed for manual and/or ultrasonic cleansing of reusable dental
      instruments. METHOD: Manufacturers/suppliers of commercially available detergents
      for manual or ultrasonic cleaning of dental instruments within primary dental
      care were invited to supply product information. A structured questionnaire
      requested details on a range of physical and chemical properties for each
      detergent. RESULTS: Seventeen detergent manufacturers/suppliers, encompassing 31
      commercially available detergents were identified. Ten of the 17 manufacturers
      provided information on 23 (74%) of the detergent formulations. Nine detergents
      were of neutral pH, ten mild alkalis (pH 7.5-10.5) and four strong alkalis (pH
      >10.5). Sixteen detergents were recommended for ultrasonic and manual cleaning,
      four stated ultrasonic use and three manual only. Ten detergents cited enzymatic
      activity as their main mode of action, but only six manufacturers provided
      detailed information. Four detergents recommended by manufacturers as suitable
      for manual washing had a strong alkaline pH (>10.5), presenting chemical hazards
      to users. Two strong alkaline detergents did not warn users of potential adverse
      effects of such alkaline solutions (corrosion) upon aluminium containing
      instruments. Only one detergent had investigated the potential toxicity of
      detergent residuals remaining on instruments after reprocessing. CONCLUSION: It
      has proven challenging to collate physico-chemical data on detergents suitable
      for use in manual and/or ultrasonic cleaning of dental instruments in general
      dental practice. Standardisation of information on the nature and efficacy of
      dental detergents in a readily accessible form would be beneficial to dental
      practice.

PMID- 22627256
TI  - Review Series--Inflammation & Fibrosis. Introduction.

PMID- 22627257
TI  - Review Series--Inflammation & Fibrosis. Fibrocytes and fibrosis.

PMID- 22627258
TI  - Outcomes of tacrolimus therapy in adults with refractory membranous nephrotic
      syndrome:  a prospective, multicenter clinical trial.
AB  - INTRODUCTION: The treatment of adult refractory idiopathic membranous nephropathy
      with steroid and other immunosuppressant-resistant nephrotic syndrome can be a
      significant challenge. The authors investigated the efficacy and safety of
      tacrolimus (TAC) as a promising regimen. METHODS: A prospective, multicenter
      trial was conducted in 9 nephrology centers from 2006 to 2008. Fourteen patients
      were enrolled. In conjunction with prednisone, TAC was started at 0.05 mg/kg/d,
      titrated to achieve a trough blood level of 5 to 10 ng/mL for the first 6 months,
      then reduced to 4 to 6 ng/mL for the subsequent 6 months. The primary endpoints
      included complete or partial remission. Secondary endpoints included relapse,
      change of clinical parameters and adverse events. RESULTS: After 12 months,
      complete remission was achieved in 35.7% of patients and partial remission in
      42.9%, yielding a response rate of 78.6%. Proteinuria, serum albumin,
      cholesterol, triglyceride and low-density lipoprotein were improved significantly
      (P < 0.001, P < 0.001, P = 0.002, P = 0.01, P = 0.004, respectively). Proteinuria
      and serum albumin were significantly improved (42.0% +/- 13.2%, P = 0.02; 15.2%
      +/- 4.5%, P = 0.01, respectively) even after the first month of treatment. One
      patient relapsed during the subsequent 6 months of follow-up. Adverse events
      included 2 cases of infection and 1 case each of hyperglycemia, hand tremor,
      sudden death (nondrug related) and diarrhea. CONCLUSIONS: TAC plus prednisone may
      be an alternative therapeutic option for steroid and general immunosuppressant
      resistant membranous nephrotic syndrome patients, with a favorable safety
      profile. However, given the limitation of a small number of patients in this
      trial, further study with a larger number and longer follow-up is needed.

PMID- 22627259
TI  - Increased expression of hypoxia-inducible factor-1alpha in proliferating
      neointimal lesions in a rat model of pulmonary arterial hypertension.
AB  - INTRODUCTION: The role of hypoxia-inducible factor-1alpha (HIF-1alpha) in
      pulmonary vascular remodeling is still undetermined. The objective of this study
      is to investigate the expression of HIF-1alpha and its role in proliferating
      neointimal lesions in a rat model of pulmonary arterial hypertension induced by
      monocrotaline (MCT) administration after left pneumonectomy. METHODS: The rats
      were subjected to MCT (60 mg/kg, subcutaneously) 7 days after left pneumonectomy
      or sham surgery; controls with vehicle treatment after left pneumonectomy or sham
      surgery were also studied. On day 35, hemodynamic parameters of the rats were
      measured. The right lower lobes of the lungs were fixed for morphometric
      analysis. The expression of proliferating cell nuclear antigen and survivin was
      detected with Western blot. The expressions of HIF-1alpha and hexokinase-2 (HK-2)
      were detected with Western blot and immunohistochemistry assay. RESULTS: The rats
      treated with MCT after pneumonectomy developed severe pulmonary arterial
      hypertension and marked medial thickening on day 35. The neointimal lesions in
      pulmonary arterioles were observed only in MCT-treated pneumonectomized rats. The
      severely injured pulmonary arterioles (intimal proliferation causing greater than
      50% luminal occlusion) accounted for 40% of all the measured arterioles in rats
      treated by MCT after pneumonectomy. The intriguing finding showed that HIF-1alpha
      was predominantly expressed in neointimal lesion areas, paralleled with the
      increased expression of HK-2 in MCT-treated pneumonectomized rats, which was not
      observed in rats undergoing MCT treatment alone. CONCLUSIONS: The activation of
      HIF-1alpha/HK-2 axis is probably the key mediator responsible for the neointimal
      lesion formation in MCT-treated pneumonectomized rats.

PMID- 22627260
TI  - Spicy seizure.
AB  - Despite the widespread use of illegal synthetic cannabinoids, report of serious
      toxicity following its use of is rare. The authors report a case of severe
      toxicity after intentional inhalation of the synthetic cannabinoid JWH-018.

PMID- 22627261
TI  - Immunofixation electrophoresis was highly specific for the diagnosis of renal
      light-chain amyloidosis.
AB  - BACKGROUND: Renal light-chain amyloidosis (AL) is one of the common causes of
      massive proteinuria and nephrotic syndrome, especially in elderly patients. This
      study aimed to evaluate the sensitivity and specificity of serum and urine using
      immunofixation electrophoresis (IFE) in the diagnosis of renal AL amyloidosis in
      patients older than 40 years. METHODS: Patients receiving native renal biopsy in
      the hospital who meet the following criteria were recruited in this retrospective
      study: (1) proteinuria excretion >=3.5 g/24 hr; (2) age >= 40 years when
      receiving renal biopsy and (3) biopsy-proven glomerulopathy. Serum and urine
      monoclonal free immunoglobulin light chains were detected using IFE. RESULTS: A
      total of 625 patients were recruited. Of them, 32 patients (5.12%) were diagnosed
      as renal AL amyloidosis. The specificities of serum, urine and serum combined
      urine IFE in the total 625 patients (ie, monoclonal free immunoglobulin light
      chain in serum or urine) for diagnosis of renal AL amyloidosis were 98.6%, 98.0%
      and 97.6%, respectively. For patients older than 60 years, the specificities of
      serum, urine and serum combined urine IFE for diagnosis of renal AL amyloidosis
      were 98.5%, 98.0% and 97.6%, respectively and the sensitivity of serum, urine and
      serum combined urine IFE for diagnosis of renal AL amyloidosis were 68.6%, 81.3%
      and 81.3%, respectively. CONCLUSION: Serum or urine IFE was highly specific for
      renal AL amyloidosis for patients older than 40 years with nephrotic-range
      proteinuria. In older patients (>60 years), both the sensitivity and specificity
      of IFE for renal AL amyloidosis were high. Combination of serum and urine IFE
      could improve the sensitivity with comparable specificity.

PMID- 22627262
TI  - Primary splenic diffuse large B-cell lymphoma in a patient with thymus Rosai
      Dorfman disease.
AB  - Rosai-Dorfman disease (RDD) is a rare macrophage-related histiocytic disorder
      that occurs primarily in lymph nodes or extranodal sites. Primary splenic
      lymphoma is an even rarer form of malignant lymphoma exhibiting characteristic
      diagnosis, treatment and outcome that have been poorly documented. Documentation
      of a rare case of primary splenic diffuse large B-cell lymphoma concomitant with
      isolated thymus RDD is reported in a 42-year-old male patient who was admitted to
      our hospital for persistent fever and splenomegaly after diagnostic thymectomy.
      On pathological review of the patient's resected thymus tissue, notable
      characteristics of thymus RDD were observed. The patient's condition quickly
      deteriorated, and the spleen progressively enlarged over the course of steroid
      treatment in our facility. Subsequent diagnostic splenectomy results indicated
      that non-Hodgkin's lymphoma (nongerminal center diffuse large B-cell lymphoma)
      was present in splenic tissues. Results of the current case study suggest that
      early exclusion of possible lymphoma is necessary in RDD patients who exhibit
      limited or no response to steroid therapy.

PMID- 22627263
TI  - Purulent pericardial effusion from community-acquired methicillin-resistant
      Staphylococcus aureus.
AB  - Although the incidence of purulent pericarditis has decreased significantly in
      the modern antibiotic era, a high index of clinical suspicion should be
      maintained to diagnose this life-threatening illness at an early stage. Community
      acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a global
      pathogen and notorious for its ability to cause infection in otherwise healthy
      individuals. However, it has been associated with purulent pericarditis only in
      some sporadic case reports. The authors describe a case of purulent pericardial
      effusion caused by CA-MRSA infection. To the best of our knowledge, this is only
      the fourth case of CA-MRSA pericarditis to be reported in English literature.

PMID- 22627264
TI  - False appearance of free air under the diaphragm.

PMID- 22627265
TI  - Spontaneously thrombosed polar renal artery aneurysm: multidetector computed
      tomography findings.

PMID- 22627266
TI  - Giant mucinous ovarian tumor.

PMID- 22627267
TI  - Hepcidin and iron regulation in health and disease.
AB  - A decade ago, hepcidin, an antimicrobial peptide with iron-regulatory properties,
      was discovered and proposed as playing a significant role in the pathogenesis of
      anemia of chronic disease. Subsequent studies have demonstrated that hepcidin is
      the keystone of the linked systems of iron balance and iron transport in health
      and in disease. The definition of the role of hepcidin and its regulation has
      permitted the mechanisms of disorders of iron homeostasis to be understood at a
      molecular level. Future studies may identify roles for hepcidin or hepcidin
      related molecules in diagnosis and therapy.

PMID- 22627268
TI  - Identification of a mechanism of transformation of clathrate hydrate structures I
      to II or H.
AB  - Binary mixed-gas hydrates including methane and other guest gases demonstrate a
      structural transition between the sI and sII phases. Under increasing pressure
      pure methane hydrate exhibits a phase transition first from sI to sII and then to
      sH. But the mechanism of the transformation from sI to sII or sH has not yet been
      identified. Recently, molecular dynamics simulations of methane hydrates suggest
      there may exist uncommon 15-hedral cages (51263), linking the sI and sII cages.
      In addition, xenon hydrate involving 15-hedral cages has been synthesized and
      named an hsI hydrate. Based on the hsI cages, we propose a mechanism for the
      transition of sI to sII or sH at atomic level resolution. The sI hydrate is first
      transformed to hsI, and hsI is further transformed to sII. Upon compression, hsI
      is transformed to sH owing to depletion of atomic layers. The mechanism of
      transformation speculated here calls for experimental verification.

PMID- 22627269
TI  - Pharmacology and therapeutic potential of pattern recognition receptors.
AB  - Pharmacologists have used pathogen-associated molecular patterns (PAMPs), such as
      lipopolysaccharide (LPS) for decades as a stimulus for studying mediators
      involved in inflammation and for the screening of anti-inflammatory compounds.
      However, in the view of immunologists, LPS was too non-specific for studying the
      mechanisms of immune signalling in infection and inflammation, as no receptors
      had been identified. This changed in the late 1990s with the discovery of the
      Toll-like receptors. These 'pattern recognition receptors' (PRRs) were able to
      recognise highly conserved sequences, the so called pathogen associated molecular
      patterns (PAMPs) present in or on pathogens. This specificity of particular PAMPs
      and their newly defined receptors provided a common ground between
      pharmacologists and immunologists for the study of inflammation. PRRs also
      recognise endogenous agonists, the so called danger-associated molecular patterns
      (DAMPs), which can result in sterile inflammation. The signalling pathways and
      ligands of many PRRs have now been characterised and there is no doubt that this
      rich vein of research will aid the discovery of new therapeutics for infectious
      conditions and chronic inflammatory disease.

PMID- 22627270
TI  - Imaging inflammation: molecular strategies to visualize key components of the
      inflammatory cascade, from initiation to resolution.
AB  - Dysregulation of inflammation is central to the pathogenesis of innumerable human
      diseases. Understanding and tracking the critical events in inflammation are
      crucial for disease monitoring and pharmacological drug discovery and
      development. Recent progress in molecular imaging has provided novel insights
      into spatial associations, molecular events and temporal sequelae in the
      inflammatory process. While remaining a burgeoning field in pre-clinical
      research, increasing application in man affords researchers the opportunity to
      study disease pathogenesis in humans in situ thereby revolutionizing conventional
      understanding of pathophysiology and potential therapeutic targets. This review
      provides a description of commonly used molecular imaging modalities, including
      optical, radionuclide and magnetic resonance imaging, and details key advances
      and translational opportunities in imaging inflammation from initiation to
      resolution.

PMID- 22627271
TI  - Drug development for severe asthma: what are the metrics?
AB  - Although reversible airway obstruction in part defines asthma, lung function as
      measured by spirometry alone inadequately predicts the value of new therapeutic
      agents in the treatment of severe asthma. Our objectives are 1) to review whether
      pulmonary function and bronchodilator reversibility are endpoints for drug
      discovery and 2) to identify parameters that predict efficacy in drug development
      in severe asthma. An English language literature search using MedLine and PubMed
      was conducted from 1997 to present concerning pathophysiology, diagnosis and
      therapy of severe asthma using the terms "severe asthma," "irreversible asthma,"
      "difficult asthma," "airway remodeling," "fixed airway obstruction,"
      "reversibility" and "bronchodilator reversibility" as index terms. Eight studies
      were characterized that encompass 1424 subjects with asthma. Our review
      identified the limitations of using bronchodilator reversibility as a predictor
      in drug development for severe asthma. Neither improvement in lung function nor
      bronchodilator reversibility characterized the benefit of new drugs in the
      treatment of severe asthma. Newly approved drugs in the treatment of severe
      asthma show decreased asthma exacerbations and improved quality of life
      associated with steroid-sparing benefits without altering bronchodilator
      responsiveness or improving lung function. Although changes in lung function
      predict asthma control in mild/moderate asthma, lung function alone is inadequate
      to assess improvement in asthma control in severe asthma manifested by fixed
      airway obstruction. Endpoints that focus on asthma control, as defined by the
      Expert Panel Report 3 and GINA guidelines, may predict the value of new
      therapeutics in the management of severe asthma.

PMID- 22627272
TI  - Primary mixed glial cultures from fetal ovine forebrain are a valid model of
      inflammation-mediated white matter injury.
AB  - Astrocytes, microglial cells and oligodendrocytes (OLs) have been employed
      separately in vitro to assess cellular pathways following a variety of stimuli.
      Mixed glial cell cultures, however, have not been utilized to the same extent,
      despite the observed discrepancy in outcomes resulting from cell-to-cell contact
      of different glia in culture. Our objective was to standardize and
      morphologically characterize a primary culture of preterm ovine glial cells in
      order to attain a relevant in vitro model to assess the intracellular effects of
      infection and inflammation. This would provide a high-throughput model necessary
      for in-depth studies on the various pathophysiological mechanisms of white matter
      injury (WMI), which may occur in the preterm infant as a consequence of maternal
      infection or the fetal inflammatory response. Glial cells from the forebrains of
      0.65-gestation ovine fetuses (comparable to 24- to 26-week human fetal brain
      development) were mechanically and enzymatically isolated and plated at a final
      density of 250,000 cells per well. When reaching confluence at 5 days after
      plating, the cultures contained astrocytes, microglial cells, as well as
      progenitor, precursor and immature OLs. Glial cell morphology and phenotypic
      immunoreactivity were characteristic of and consistent with previous observations
      of separately cultured cell types. To determine the effects of infection or
      inflammation in our in vitro model, we then treated mixed glial cultures with
      tumour necrosis factor-alpha (TNF-alpha; 50 or 100 ng/ml) or lipopolysaccharide
      (LPS; 1 ug/ml) for a period of 48 h. Cytokine levels were measured by ELISA and
      cell numbers for specific glial cell types were determined along with OL
      proliferation and apoptosis by Ki67 and caspase-3 immunocytochemistry,
      respectively. Our results showed that exposure to TNF-alpha or LPS resulted in a
      characteristic inflammatory response entailed by up-regulation of pro
      inflammatory cytokines, a lack of astrogliosis and a marked reduction in OLs
      attributable to increased apoptosis. In LPS-treated cultures, there was a marked
      increase in the pro-inflammatory cytokine TNF-alpha at both 24 and 48 h. In
      conclusion, this is the first report of the immunocytochemical description and
      characterization of fetal ovine-derived mixed glial cell primary cultures. This
      in vitro model provides a novel and efficient system to explore the mechanisms of
      infection/inflammation-mediated WMI at the cellular level and for screening
      candidate therapeutic strategies.

PMID- 22627273
TI  - Neutrophil gelatinase-associated lipocalin: a novel marker of contrast
      nephropathy risk.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL, siderocalin) is a
      protein secreted by the kidney in the setting of acute kidney injury in an
      attempt to regulate and bind the release of catalytic iron from injured cells. We
      sought to evaluate the relationships between baseline NGAL, renal filtration
      function, and the degree of injury reflected by further increases in NGAL.
      METHODS: This study was a prospective, blinded assessment of blood samples taken
      from patients with estimated glomerular filtration rate (eGFR) <75 ml/min/1.73
      m(2) undergoing non-urgent coronary angiography and intervention using iodinated
      contrast. Renal transplant recipients, dialysis patients, and administration of
      iodinated contrast in the prior 30 days were exclusion criteria. Plasma NGAL was
      measured using the AlereTM assay. Serum creatinine (Cr) was measured using
      calibrated methods at a core laboratory. Samples were obtained at baseline, 1, 2,
      4, 6, 12, 24, and 48 h after contrast administration. RESULTS: A total of 63
      subjects were enrolled with a mean age of 69.4 +/- 9.1 years, 73% male, 35% with
      diabetes, and a mean eGFR of 47.82 +/- 15.46 ml/min/1.73 m(2). The correlation
      between eGFR and NGAL was r = -0.61, 95% CI -0.74 to -0.44, p < 0.001. When
      stratified by baseline NGAL tertile, the peak NGAL observed for each group
      occurred at 29.0 +/- 22.2 h and there was a twofold increase in the mean and peak
      change in NGAL across the tertiles. NGAL began to rise 6 h after contrast
      exposure and followed a similar course to serum Cr and at 48 h the overall mean
      NGAL was still rising. Only 2 patients sustained a rise in Cr of >25% or >=0.5
      mg/dl. Multivariate regression revealed that baseline NGAL (p < 0.001) and not
      eGFR (p = 0.95) was independently associated with the NGAL value at 48 h.
      CONCLUSIONS: Baseline NGAL is strongly correlated with eGFR in patients with
      reduced renal filtration function undergoing coronary angiography. The magnitude
      of rise in NGAL is positively associated with the baseline value and is analogous
      to the time course of Cr in blood after contrast exposure. NGAL and not eGFR is
      an independent predictor of changes in the post-procedure NGAL. A baseline NGAL
      level is necessary for the interpretation of NGAL levels in the evaluation of
      acute kidney injury.

PMID- 22627274
TI  - Wafer-scale mitochondrial membrane potential assays.
AB  - It has been reported that mitochondrial metabolic and biophysical parameters are
      associated with degenerative diseases and the aging process. To evaluate these
      biochemical parameters, current technology requires several hundred milligrams of
      isolated mitochondria for functional assays. Here, we demonstrate manufacturable
      wafer-scale mitochondrial functional assay lab-on-a-chip devices, which require
      mitochondrial protein quantities three orders of magnitude less than current
      assays, integrated onto 4'' standard silicon wafer with new fabrication processes
      and materials. Membrane potential changes of isolated mitochondria from various
      well-established cell lines such as human HeLa cell line (Heb7A), human
      osteosarcoma cell line (143b) and mouse skeletal muscle tissue were investigated
      and compared. This second generation integrated lab-on-a-chip system developed
      here shows enhanced structural durability and reproducibility while increasing
      the sensitivity to changes in mitochondrial membrane potential by an order of
      magnitude as compared to first generation technologies. We envision this system
      to be a great candidate to substitute current mitochondrial assay systems.

PMID- 22627275
TI  - Hydrogen bond-assisted macrocyclic oligocholate transporters in lipid membranes.
AB  - Three macrocyclic oligocholates containing a carboxyl group, a guanidinium ion,
      and a Cbz-protected amine, respectively, were studied as membrane transporters
      for hydrophilic molecules. To permeate glucose across lipid bilayers, the
      macrocycles stacked over one another to form a transmembrane nanopore, driven by
      a strong tendency of the water molecules in the internal cavities of the
      amphiphilic macrocycles to aggregate in a nonpolar environment. To transport
      larger guests such as carboxyfluorescein (CF), the macrocycles acted as carriers
      to shuttle the guest across the membrane. Hydrogen-bonds between the side chains
      of the macrocycles strongly affected the transport properties. Surprisingly, the
      carboxyl group turned out to be far more effective at assisting the aggregation
      of the oligocholate macrocycles in the membrane than the much stronger
      carboxylate-guanidinium salt bridge, likely due to competition from the phosphate
      groups of the lipids for the guanidinium.

PMID- 22627276
TI  - Height and torsional stiffness are most sensitive to annular injury in large
      animal intervertebral discs.
AB  - BACKGROUND CONTEXT: Acute annulus fibrosus injury has been identified as a
      contributing factor to intervertebral disc (IVD) degeneration. Injuries as small
      as those resulting from needle injection result in localized mechanical
      disruption via fiber breakage, but it is unknown whether these injuries initiate
      degeneration locally or through changes in the mechanical behavior of the entire
      disc. However, in vitro biomechanical studies of injury are limited to a single
      type of injury or measurements in only one or two degrees of freedom. PURPOSE:
      The aim of this study is to provide a comprehensive assessment of the joint level
      mechanical response to IVD injuries of various sizes in a large animal model. We
      hypothesize that annular injuries will affect disc mechanics differently
      depending on size, location, and mode of loading. We further hypothesize that a
      large injury to one side of the disc will induce a bending moment reaction under
      axial compression, which may decrease spinal column stability. STUDY DESIGN: A
      comprehensive biomechanical study investigating effects of small and large
      injuries on IVD pressurization and six-degree-of-freedom stiffness behaviors
      using bovine motion segments. METHODS: Bovine caudal motion segments were
      subjected to a series of annular injuries ranging from 21-gauge needle puncture
      to 10-mm scalpel incisions and evaluated before and after injury with both
      mechanical testing under multiple degrees of freedom (axial compression, flexion
      extension, lateral bending, and torsion) and nucleus pulposus (NP) fluid
      pressurization tests. RESULTS: Mechanical tests showed that axial torsional
      stiffness and disc height under resting compressive load were the parameters most
      sensitive to large annular injury. Bending and compressive stiffnesses, as well
      as bending moments induced by axial compression, were not significantly changed
      by scalpel incisions. Additionally, large injuries resulted in altered relaxation
      behavior after NP pressurization indicative of increases in both radial bulge
      compliance and fluid flow rates. CONCLUSIONS: These findings suggest that loss of
      disc height, torsional stiffness, and NP fluid pressurization are the immediate
      results of acute annular injury and are therefore those properties that IVD
      repair strategies must strive to restore or maintain. The lack of change in
      bending stiffness and moment under compression suggests that acute annular tears
      alone are not sufficient to induce off-axis motion and instability.

PMID- 22627277
TI  - A Bayesian non-parametric Potts model with application to pre-surgical FMRI data.
AB  - The Potts model has enjoyed much success as a prior model for image segmentation.
      Given the individual classes in the model, the data are typically modeled as
      Gaussian random variates or as random variates from some other parametric
      distribution. In this article, we present a non-parametric Potts model and apply
      it to a functional magnetic resonance imaging study for the pre-surgical
      assessment of peritumoral brain activation. In our model, we assume that the Z
      score image from a patient can be segmented into activated, deactivated, and null
      classes, or states. Conditional on the class, or state, the Z-scores are assumed
      to come from some generic distribution which we model non-parametrically using a
      mixture of Dirichlet process priors within the Bayesian framework. The posterior
      distribution of the model parameters is estimated with a Markov chain Monte Carlo
      algorithm, and Bayesian decision theory is used to make the final
      classifications. Our Potts prior model includes two parameters, the standard
      spatial regularization parameter and a parameter that can be interpreted as the a
      priori probability that each voxel belongs to the null, or background state,
      conditional on the lack of spatial regularization. We assume that both of these
      parameters are unknown, and jointly estimate them along with other model
      parameters. We show through simulation studies that our model performs on par, in
      terms of posterior expected loss, with parametric Potts models when the
      parametric model is correctly specified and outperforms parametric models when
      the parametric model in misspecified. 

PMID- 22627278
TI  - Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and
      vascular development.
AB  - Molecular oxygen is essential for the development, growth and survival of
      multicellular organisms. Hypoxic microenvironments and oxygen gradients are
      generated physiologically during embryogenesis and organogenesis. In the eye,
      oxygen plays a crucial role in both physiological vascular development and common
      blinding diseases. The retinal pigment epithelium (RPE) is a monolayer of cells
      essential for normal ocular development and in the mature retina provides support
      for overlying photoreceptors and their vascular supply. Hypoxia at the level of
      the RPE is closely implicated in pathogenesis of age-related macular
      degeneration. Adaptive tissue responses to hypoxia are orchestrated by
      sophisticated oxygen sensing mechanisms. In particular, the von Hippel-Lindau
      tumour suppressor protein (pVhl) controls hypoxia-inducible transcription factor
      (HIF)-mediated adaptation. However, the role of Vhl/Hif1a in the RPE in the
      development of the eye and its vasculature is unknown. In this study we explored
      the function of Vhl and Hif1a in the developing RPE using a tissue-specific
      conditional-knockout approach. We found that deletion of Vhl in the RPE results
      in RPE apoptosis, aniridia and microphthalmia. Increased levels of Hif1a, Hif2a,
      Epo and Vegf are associated with a highly disorganised retinal vasculature,
      chorioretinal anastomoses and the persistence of embryonic vascular structures
      into adulthood. Additional inactivation of Hif1a in the RPE rescues the RPE
      morphology, aniridia, microphthalmia and anterior vasoproliferation, but does not
      rescue retinal vasoproliferation. These data demonstrate that Vhl-dependent
      regulation of Hif1a in the RPE is essential for normal RPE and iris development,
      ocular growth and vascular development in the anterior chamber, whereas Vhl
      dependent regulation of other downstream pathways is crucial for normal
      development and maintenance of the retinal vasculature.

PMID- 22627279
TI  - Gut endoderm is involved in the transfer of left-right asymmetry from the node to
      the lateral plate mesoderm in the mouse embryo.
AB  - In the mouse, the initial signals that establish left-right (LR) asymmetry are
      determined in the node by nodal flow. These signals are then transferred to the
      lateral plate mesoderm (LPM) through cellular and molecular mechanisms that are
      not well characterized. We hypothesized that endoderm might play a role in this
      process because it is tightly apposed to the node and covers the outer surface of
      the embryo, and, just after nodal flow is established, higher Ca(2+) flux has
      been reported on the left side near the node, most likely in the endoderm cells.
      Here we studied the role of endoderm cells in the transfer of the LR asymmetry
      signal by analyzing mouse Sox17 null mutant embryos, which possess endoderm
      specific defects. Sox17(-/-) embryos showed no expression or significantly
      reduced expression of LR asymmetric genes in the left LPM. In Sox17 mutant
      endoderm, the localization of connexin proteins on the cell membrane was greatly
      reduced, resulting in defective gap junction formation, which appeared to be
      caused by incomplete development of organized epithelial structures. Our findings
      suggest an essential role of endoderm cells in the signal transfer step from the
      node to the LPM, possibly using gap junction communication to establish the LR
      axis of the mouse.

PMID- 22627281
TI  - lyve1 expression reveals novel lymphatic vessels and new mechanisms for lymphatic
      vessel development in zebrafish.
AB  - We have generated novel transgenic lines that brightly mark the lymphatic system
      of zebrafish using the lyve1 promoter. Facilitated by these new transgenic lines,
      we generated a map of zebrafish lymphatic development up to 15 days post
      fertilisation and discovered three previously uncharacterised lymphatic vessel
      networks: the facial lymphatics, the lateral lymphatics and the intestinal
      lymphatics. We show that a facial lymphatic vessel, termed the lateral facial
      lymphatic, develops through a novel developmental mechanism, which initially
      involves vessel growth through a single vascular sprout followed by the
      recruitment of lymphangioblasts to the vascular tip. Unlike the lymphangioblasts
      that form the thoracic duct, the lymphangioblasts that contribute to the lateral
      facial lymphatic vessel originate from a number of different blood vessels. Our
      work highlights the additional complexity of lymphatic vessel development in the
      zebrafish that may increase its versatility as a model of lymphangiogenesis.

PMID- 22627280
TI  - Olig2-dependent developmental fate switch of NG2 cells.
AB  - NG2-expressing cells (NG2 cells or polydendrocytes) generate oligodendrocytes
      throughout the CNS and a subpopulation of protoplasmic astrocytes in the gray
      matter of the ventral forebrain. The mechanisms that regulate their
      oligodendrocyte or astrocyte fate and the degree to which they exhibit lineage
      plasticity in vivo have remained unclear. The basic helix-loop-helix
      transcription factor Olig2 is required for oligodendrocyte specification and
      differentiation. We have found that Olig2 expression is spontaneously
      downregulated in NG2 cells in the normal embryonic ventral forebrain as they
      differentiate into astrocytes. To further examine the role of Olig2 in NG2 cell
      fate determination, we used genetic fate mapping of NG2 cells in constitutive and
      tamoxifen-inducible Olig2 conditional knockout mice in which Olig2 was deleted
      specifically in NG2 cells. Constitutive deletion of Olig2 in NG2 cells in the
      neocortex and corpus callosum but not in ventral forebrain caused them to convert
      their fate into astrocytes, with a concomitant severe reduction in the number of
      oligodendrocytes and myelin. Deletion of Olig2 in NG2 cells in perinatal mice
      also resulted in astrocyte generation from neocortical NG2 cells. These
      observations indicate that the developmental fate of NG2 cells can be switched by
      altering a single transcription factor Olig2.

PMID- 22627282
TI  - Distinct developmental origins and regulatory mechanisms for GABAergic neurons
      associated with dopaminergic nuclei in the ventral mesodiencephalic region.
AB  - GABAergic neurons in the ventral mesodiencephalic region are highly important for
      the function of dopaminergic pathways that regulate multiple aspects of behavior.
      However, development of these neurons is poorly understood. We recently showed
      that molecular regulation of differentiation of the GABAergic neurons associated
      with the dopaminergic nuclei in the ventral midbrain (VTA and SNpr) is distinct
      from the rest of midbrain, but the reason for this difference remained elusive.
      Here, we have analyzed the developmental origin of the VTA and SNpr GABAergic
      neurons by genetic fate mapping. We demonstrate that the majority of these
      GABAergic neurons originate outside the midbrain, from rhombomere 1, and move
      into the ventral midbrain only as postmitotic neuronal precursors. We further
      show that Gata2, Gata3 and Tal1 define a subpopulation of GABAergic precursors in
      ventral rhombomere 1. A failure in GABAergic neuron differentiation in this
      region correlates with loss of VTA and SNpr GABAergic neurons in Tal1 mutant
      mice. In contrast to midbrain, GABAergic neurons of the anterior SNpr in the
      diencephalon are not derived from the rhombomere 1. These results suggest unique
      migratory pathways for the precursors of important GABAergic neuron
      subpopulations, and provide the basis for understanding diversity within midbrain
      GABAergic neurons.

PMID- 22627283
TI  - Hedgehog-dependent proliferation drives modular growth during morphogenesis of a
      dermal bone.
AB  - In the developing skeleton, dermal bone morphogenesis includes the balanced
      proliferation, recruitment and differentiation of osteoblast precursors, yet how
      bones acquire unique morphologies is unknown. We show that Hedgehog (Hh)
      signaling mediates bone shaping during early morphogenesis of the opercle (Op), a
      well characterized dermal bone of the zebrafish craniofacial skeleton. ihha is
      specifically expressed in a local population of active osteoblasts along the
      principal growing edge of the bone. Mutational studies show that Hh signaling by
      this osteoblast population is both necessary and sufficient for full recruitment
      of pre-osteoblasts into the signaling population. Loss of ihha function results
      in locally reduced proliferation of pre-osteoblasts and consequent reductions in
      recruitment into the osteoblast pool, reduced bone edge length and reduced
      outgrowth. Conversely, hyperactive Hh signaling in ptch1 mutants causes opposite
      defects in proliferation and growth. Time-lapse microscopy of early Op
      morphogenesis using transgenically labeled osteoblasts demonstrates that ihha
      dependent bone development is not only region specific, but also begins exactly
      at the onset of a second phase of morphogenesis, when the early bone begins to
      reshape into a more complex form. These features strongly support a hypothesis
      that dermal bone development is modular, with different gene sets functioning at
      specific times and locations to pattern growth. The Hh-dependent module is not
      limited to this second phase of bone growth: during later larval development, the
      Op is fused along the dysmorphic edge to adjacent dermal bones. Hence, patterning
      within a module may include adjacent regions of functionally related bones and
      might require that signaling pathways function over an extended period of
      development.

PMID- 22627284
TI  - Hyperproliferation of mitotically active germ cells due to defective anti
      Mullerian hormone signaling mediates sex reversal in medaka.
AB  - The function of AMH (Anti-Mullerian hormone), a phylogenetically ancient member
      of the TGFbeta family of proteins, in lower vertebrates is largely unknown.
      Previously, we have shown that the gene encoding the type II anti-Mullerian
      hormone receptor, amhrII, is responsible for excessive germ cell proliferation
      and male-to-female sex reversal in the medaka hotei mutant. In this study,
      functional analyses in cultured cells and of other amhrII mutant alleles indicate
      that lack of AMH signaling causes the hotei phenotype. BrdU incorporation
      experiments identified the existence of both quiescent and mitotically active
      germ cells among the self-renewing, type I population of germ cells in the
      developing gonad. AMH signaling acts in supporting cells to promote the
      proliferation of mitotically active germ cells but does not trigger quiescent
      germ cells to proliferate in the developing gonad. Furthermore, we show that the
      male-to-female sex reversal phenotype in hotei mutants is not a direct
      consequence of AMH signaling in supporting cells, but is instead mediated by germ
      cells. Our data demonstrate that interfollicular AMH signaling regulates
      proliferation at a specific stage of germ cell development, and that this
      regulation is crucial for the proper manifestation of gonadal sex directed by sex
      determination genes.

PMID- 22627285
TI  - Novel mechanisms of early upper and lower urinary tract patterning regulated by
      RetY1015 docking tyrosine in mice.
AB  - Mutations in the receptor tyrosine kinase RET are associated with congenital
      anomalies of kidneys or urinary tract (CAKUT). RET tyrosine Y1015 is the docking
      site for PLCgamma, a major regulator of RET signaling. Abrogating signaling via
      Y1015 causes CAKUT that are markedly different than renal agenesis in Ret-null or
      RetY1062F mutant mice. We performed analysis of Y1015F mutant upper and lower
      urinary tracts in mice to delineate its molecular and developmental roles during
      early urinary tract formation. We found that the degeneration of the common
      nephric ducts (CND), the caudal-most Wolffian duct (WD) segment, depends on Y1015
      signals. The CNDs in Y1015F mutants persist owing to increased proliferation and
      reduced apoptosis, and showed abundance of phospho-ERK-positive cells. In the
      upper urinary tract, the Y1015 signals are required for proper patterning of the
      mesonephros and metanephros. Timely regression of mesonephric mesenchyme and
      proper demarcation of mesonephric and metanephric mesenchyme from the WD depends
      on RetY1015 signaling. We show that the mechanism of de novo ectopic budding is
      via increased ERK activity due to abnormal mesenchymal GDNF expression. Although
      reduction in GDNF dosage improved CAKUT it did not affect delayed mesenchyme
      regression. Experiments using whole-mount immunofluorescence confocal microscopy
      and explants cultures of early embryos with ERK-specific inhibitors suggest an
      imbalance between increased proliferation, decreased apoptosis and increased ERK
      activity as a mechanism for WD defects in RetY1015F mice. Our work demonstrates
      novel inhibitory roles of RetY1015 and provides a possible mechanistic
      explanation for some of the confounding broad range phenotypes in individuals
      with CAKUT.

PMID- 22627286
TI  - In vitro generation of mature dopamine neurons by decreasing and delaying the
      expression of exogenous Nurr1.
AB  - Neural stem/progenitor cell (NSC/NPC) cultures can be a source of dopamine (DA)
      neurons for experimental and transplantation purposes. Nurr1, a steroid receptor
      transcription factor, can overcome the limitations associated with
      differentiation of cultured NPCs into DA neurons. However, forced Nurr1
      expression in NPC cultures generates non-neuronal and/or immature DA cells. We
      show here that the Nurr1 level and period of expression crucially affect the
      differentiation and maturation of Nurr1-induced DA neurons. Mature DA neurons
      were generated by manipulating Nurr1 expression patterns to resemble those in the
      developing midbrain.

PMID- 22627287
TI  - FGF signaling establishes the anterior border of the Ciona neural tube.
AB  - The Ciona tadpole is constructed from simple, well-defined cell lineages governed
      by provisional gene networks that have been defined via extensive gene disruption
      assays. Here, we examine the patterning of the anterior neural plate, which
      produces placodal derivatives such as the adhesive palps and stomodeum, as well
      as the sensory vesicle (simple brain) of the Ciona tadpole. Evidence is presented
      that the doublesex-related gene DMRT is expressed throughout the anterior neural
      plate of neurulating embryos. It leads to the activation of FoxC and ZicL in the
      palp placode and anterior neural tube, respectively. This differential expression
      depends on FGF signaling, which inhibits FoxC expression in the anterior neural
      tube. Inhibition of FGF signaling leads to expanded expression of FoxC, the loss
      of ZicL, and truncation of the anterior neural tube.

PMID- 22627289
TI  - Coffee, colon function and colorectal cancer.
AB  - For several years the physiological effects of coffee have been focused on its
      caffeine content, disregarding the hundreds of bioactive coffee components, such
      as polyphenols, melanoidins, carbohydrates, diterpenes, etc. These compounds may
      exert their protection against colorectal cancer (CRC), the third most common
      cancer worldwide. However, the amount and type of compounds ingested with the
      beverage may be highly different depending on the variety of coffee used, the
      roasting degree, the type of brewing method as well as the serving size. In this
      frame, this paper reviews the mechanisms by which coffee may influence the risk
      of CRC development focusing on espresso and filtered coffee, as well as on the
      components that totally or partially reach the colon i.e. polyphenols and dietary
      fiber, including melanoidins. In particular the effects of coffee on some colon
      conditions whose deregulation may lead to cancer, namely microbiota composition
      and lumen reducing environment, were considered. Taken together the discussed
      studies indicated that, due to their in vivo metabolism and composition, both
      coffee chlorogenic acids and dietary fiber, including melanoidins, may reduce CRC
      risk, increasing colon motility and antioxidant status. Further studies should
      finally assess whether the coffee benefits for colon are driven through a
      prebiotic effect.

PMID- 22627288
TI  - beta-Catenin gain of function in muscles impairs neuromuscular junction
      formation.
AB  - Neuromuscular junction (NMJ) formation requires proper interaction between
      motoneurons and muscle cells. beta-Catenin is required in muscle cells for NMJ
      formation. To understand underlying mechanisms, we investigated the effect of
      beta-catenin gain of function (GOF) on NMJ development. In HSA-beta
      cat(flox(ex3)/+) mice, which express stable beta-catenin specifically in muscles,
      motor nerve terminals became extensively defasciculated and arborized. Ectopic
      muscles were observed in the diaphragm and were innervated by ectopic phrenic
      nerve branches. Moreover, extensive outgrowth and branching of spinal axons were
      evident in the GOF mice. These results indicate that increased beta-catenin in
      muscles alters presynaptic differentiation. Postsynaptically, AChR clusters in
      HSA-beta-cat(flox(ex3)/+) diaphragms were distributed in a wider region,
      suggesting that muscle beta-catenin GOF disrupted the signal that restricts AChR
      clustering to the middle region of muscle fibers. Expression of stable beta
      catenin in motoneurons, however, had no effect on NMJ formation. These
      observations provide additional genetic evidence that pre- and postsynaptic
      development of the NMJ requires an intricate balance of beta-catenin activity in
      muscles.

PMID- 22627290
TI  - Drosophila apc regulates delamination of invasive epithelial clusters.
AB  - Border Cells in the Drosophila ovaries are a useful genetic model for
      understanding the molecular events underlying epithelial cell motility. During
      stage 9 of egg chamber development they detach from neighboring stretched cells
      and migrate between the nurse cells to reach the oocyte. RNAi screening allowed
      us to identify the dapc1 gene as being critical in this process. Clonal and live
      analysis showed a requirement of dapc1 in both outer border cells and contacting
      stretched cells for delamination. This mutant phenotype was rescued by dapc1 or
      dapc2 expression. Loss of dapc1 function was associated with an abnormal lasting
      accumulation of beta-catenin/Armadillo and E-cadherin at the boundary between
      migrating border and stretched cells. Moreover, beta-catenin/armadillo or E
      cadherin downregulation rescued the dapc1 loss of function phenotype. Altogether
      these results indicate that Drosophila Apc1 is required for dynamic remodeling of
      beta-catenin/Armadillo and E-cadherin adhesive complexes between outer border
      cells and stretched cells regulating proper delamination and invasion of
      migrating epithelial clusters.

PMID- 22627293
TI  - Autophagy acts as a safeguard mechanism against G-quadruplex ligand-mediated DNA
      damage.
AB  - G-quadruplex ligands have attracted considerable interest as novel anticancer
      therapeutics due to their capability to interfere with guanosine-rich DNA/RNA
      sequences, such as telomeres. Elucidation of the structures of telomeric G
      quadruplexes has led, in the past few years, to the rational development of
      effective G-quadruplex-stabilizing small molecules. In the present study, we
      showed that short-term exposure of melanoma cells to Ant1,5--an anthracene-based
      ligand able to stabilize telomeric G-quadruplexes--impaired cell growth without
      inducing cell senescence or apoptosis. Conversely, drug-treated cells were
      characterized by the occurrence of typical biochemical and morphological features
      associated with autophagy, such as an increase in the lipidated form of the
      autophagic marker LC3B and the accumulation of autophagosomes. Such drug-induced
      autophagy occurred as a consequence of DNA damage induction, at least in part
      dependent on drug-mediated telomere uncapping, through a pathway converging on
      the cyclin-dependent kinase inhibitor 1A (CDKN1A/p21). Indeed, melanoma cells
      depleted for CDKN1A did not show evidence of autophagic markers upon exposure to
      Ant1,5. The inhibition of autophagy by a pharmacologic inhibitor or through RNAi
      mediated depletion of the ATG5 gene enhanced the cytotoxic activity of Ant1,5, as
      revealed by the marked increase in drug-induced apoptosis. Our data outline a
      molecular scenario in which G-quadruplex ligand-induced telomeric dysfunctions
      and DNA damage are translated into an autophagic response and provide the first
      evidence of autophagy as a safeguard mechanism activated by melanoma cells to
      counteract G-quadruplex ligand-mediated cellular stress.

PMID- 22627291
TI  - Visualization of retinoic acid signaling in transgenic axolotls during limb
      development and regeneration.
AB  - Retinoic acid (RA) plays a necessary role in limb development and regeneration,
      but the precise mechanism by which it acts during these processes is unclear. The
      role of RA in limb regeneration was first highlighted by the remarkable effect
      that it has on respecifying the proximodistal axis of the regenerating limb so
      that serially repeated limbs are produced. To facilitate the study of RA
      signaling during development and then during regeneration of the same structure
      we have turned to the axolotl, the master of vertebrate regeneration, and
      generated transgenic animals that fluorescently report RA signaling in vivo.
      Characterization of these animals identified an anterior segment of the
      developing embryo where RA signaling occurs revealing conserved features of the
      early vertebrate embryo. During limb development RA signaling was present in the
      developing forelimb bud mesenchyme, but was not detected during hindlimb
      development. During limb regeneration, RA signaling was surprisingly almost
      exclusively observed in the apical epithelium suggesting a different role of RA
      during limb regeneration. After the addition of supplemental RA to regenerating
      limbs that leads to pattern duplications, the fibroblast stem cells of the
      blastema responded showing that they are capable of transcriptionally responding
      to RA. These findings are significant because it means that RA signaling may play
      a multifunctional role during forelimb development and regeneration and that the
      fibroblast stem cells that regulate proximodistal limb patterning during
      regeneration are targets of RA signaling.

PMID- 22627292
TI  - Transcriptional integration of Wnt and Nodal pathways in establishment of the
      Spemann organizer.
AB  - Signaling inputs from multiple pathways are essential for the establishment of
      distinct cell and tissue types in the embryo. Therefore, multiple signals must be
      integrated to activate gene expression and confer cell fate, but little is known
      about how this occurs at the level of target gene promoters. During early
      embryogenesis, Wnt and Nodal signals are required for formation of the Spemann
      organizer, which is essential for germ layer patterning and axis formation.
      Signaling by both Wnt and Nodal pathways is required for the expression of
      multiple organizer genes, suggesting that integration of these signals is
      required for organizer formation. Here, we demonstrate transcriptional
      cooperation between the Wnt and Nodal pathways in the activation of the organizer
      genes Goosecoid (Gsc), Cerberus (Cer), and Chordin (Chd). Combined Wnt and Nodal
      signaling synergistically activates transcription of these organizer genes.
      Effectors of both pathways occupy the Gsc, Cer and Chd promoters and effector
      occupancy is enhanced with active Wnt and Nodal signaling. This suggests that, at
      organizer gene promoters, a stable transcriptional complex containing effectors
      of both pathways forms in response to combined Wnt and Nodal signaling.
      Consistent with this idea, the histone acetyltransferase p300 is recruited to
      organizer promoters in a Wnt and Nodal effector-dependent manner. Taken together,
      these results offer a mechanism for spatial and temporal restriction of organizer
      gene transcription by the integration of two major signaling pathways, thus
      establishing the Spemann organizer domain.

PMID- 22627294
TI  - Clioquinol induces DNA double-strand breaks, activation of ATM, and subsequent
      activation of p53 signaling.
AB  - Clioquinol, a Cu2+/Zn2+/Fe2+ chelator/ionophor, was used extensively in the mid
      1900s as an amebicide for treating indigestion and diarrhea. It was eventually
      withdrawn from the market because of a link to subacute myelo-optic neuropathy
      (SMON) in Japan. The pathogenesis of SMON, however, is not fully understood. To
      clarify the molecular mechanisms of clioquinol-induced neurotoxicity, a global
      analysis using DNA chips was carried out on human neuroblastoma cells. The global
      analysis and quantitative PCR demonstrated that mRNA levels of p21(Cip1), an
      inhibitor of cyclins D and E, and of GADD45alpha, a growth arrest and DNA damage
      inducible protein, were significantly increased by clioquinol treatment in SH
      SY5Y and IMR-32 neuroblastoma cells. Activation of p53 by clioquinol was
      suggested, since clioquinol induced phosphorylation of p53 at Ser15 to enhance
      its stabilization. The phosphorylation of p53 was inhibited by KU-55933, an
      inhibitor of ataxia-telangiectasia mutated kinase (ATM), but not by NU7026, an
      inhibitor of DNA-dependent protein kinase (DNA-PK). Clioquinol in fact induced
      phosphorylation of ATM and histone H2AX, a marker of DNA double-strand breaks
      (DSBs). These results suggest that clioquinol-induced neurotoxicity is mediated
      by DSBs and subsequent activation of ATM/p53 signaling.

PMID- 22627295
TI  - Aroclor 1254 selectively inhibits expression of glial GLT-1 glutamate transporter
      in the forebrain of chronically exposed adult rat.
AB  - Aroclor 1254, a commercially produced mixture of polychlorinated biphenyls, is
      known to cause many adverse conditions, including neurotoxicity. It has been
      recently postulated that upregulation of N-methyl-d-aspartate receptors (NMDARs)
      and enhanced glutamate signalling which leads to excitotoxicity, is the mechanism
      of Aroclor-induced neurotoxicity. To obtain insights into the mechanisms
      underlying glutamatergic overstimulation, we investigated the function and
      expression of sodium-dependent glutamate transporters which are known to regulate
      extracellular glutamate concentrations in the brain. Exposure to Aroclor 1254 was
      found to significantly lower the uptake of radioactive glutamate into gliosomal
      fractions obtained from adult rat brains. It also markedly decreased the
      expression of both protein and mRNA of GLT-1, the main glial glutamate
      transporter. This indicates that downregulation of GLT-1 may potentially lead to
      disturbances in glutamate clearance. The expression of GLAST, another astroglial
      glutamate transporter, was unchanged under conditions of Aroclor toxicity.
      Conversely, we observed enhanced glutamate uptake into nerve-endings fractions
      paralleled by increased EAAC1 protein expression. This may reflect the induction
      of protective mechanisms.

PMID- 22627296
TI  - Implication of oxidative stress in size-dependent toxicity of silica
      nanoparticles in kidney cells.
AB  - Silica nanoparticles (nano-SiO(2)) are one of the most popular nanomaterials used
      in industrial manufacturing, synthesis, engineering and medicine. While
      inhalation of nanoparticles causes pulmonary damage, nano-SiO(2) can be
      transported into the blood and deposit in target organs where they exert
      potential toxic effects. Kidney is considered as such a secondary target organ.
      However, toxicological information of their effect on renal cells and the
      mechanisms involved remain sparse. In the present study, the cytotoxicity of nano
      SiO(2) of different sizes was investigated on two renal proximal tubular cell
      lines (human HK-2 and porcine LLC-PK(1)). The molecular pathways involved were
      studied with a focus on the involvement of oxidative stress. Nanoparticle
      characterization was performed (primary nanoparticle size, surface area,
      dispersion) in order to investigate a potential relationship between their
      physical properties and their toxic effects. Firstly, evidence of particle
      internalization was obtained by transmission electron microscopy and conventional
      flux cytometry techniques. The use of specific inhibitors of endocytosis pathways
      showed an internalization process by macropinocytosis and clathrin-mediated
      endocytosis for 100 nm nano-SiO(2) nanoparticles. These nanoparticles were
      localized in vesicles. Toxicity was size- and time-dependent (24h, 48 h, 72 h).
      Indeed, it increased as nanoparticles became smaller. Secondly, analysis of
      oxidative stress based on the assessment of ROS (reactive oxygen species)
      production (DHE, dihydroethidium) or lipid peroxidation (MDA, malondialdehyde)
      clearly demonstrated the involvement of oxidative stress in the toxicity of 20 nm
      nano-SiO(2). The induction of antioxidant enzymes (catalase, GSTpi, thioredoxin
      reductase) could explain their lesser toxicity with 100 nm nano-SiO(2).

PMID- 22627297
TI  - The stress caused by nitrite with titanium dioxide nanoparticles under UVA
      irradiation in human keratinocyte cell.
AB  - Our previous work found that in the presence of nitrite, titanium dioxide
      nanoparticles can cause protein tyrosine nitration under UVA irradiation in vivo.
      In this paper, the human keratinocyte cells was used as a skin cell model to
      further study the photo-toxicity of titanium dioxide nanoparticles when nitrite
      was present. The results showed that nitrite increased the photo-toxicity of
      titanium dioxide in a dose-dependant manner, and generated protein tyrosine
      nitration in keratinocyte cells. Morphological study of keratinocyte cells
      suggested a specific apoptosis mediated by apoptosis inducing factor. It was also
      found the main target nitrated in cells was cystatin-A, which expressed
      abundantly in cytoplasm and functioned as a cysteine protease inhibitor. The
      stress induced by titanium dioxide with nitrite under UVA irradiation in human
      keratinocyte cells appeared to trigger the apoptosis inducing factor mediated
      cell death and lose the inhibition of active caspase by cystatin-A. We conclude
      that nitrite can bring new damage and stress to human keratinocyte cells with
      titanium dioxide nanoparticles under UVA irradiation.

PMID- 22627298
TI  - Comparison of the adverse events associated with MF59-adjuvanted and non
      adjuvanted H1N1 vaccines in healthy young male Korean soldiers.
AB  - The first large-scale outbreaks of respiratory disease in the 21st century were 
      caused by the influenza A (H1N1) virus in 2009, which affected mostly young
      adults. The M59  vaccine was developed to control pandemic influenza A (H1N1).
      However, the complications  arising from the use of the non-adjuvanted and
      adjuvanted vaccines in young male Korean soldiers  have not previously been
      evaluated and compared. We conducted a prospective multicenter study  of 2,864
      healthy male soldiers aged 19 to 25 years to evaluate the adverse events
      associated  with both the MF59-adjuvanted and non-adjuvanted forms of the
      influenza A/California/2009  (H1N1) surface-antigen vaccine. In most cases, the
      adverse-event symptoms were mild, and the  most frequent adverse events were
      swelling at the injection site and myalgia, which were noted  in 4.8% and 10.7%
      of participants, respectively. Administration of the MF59-adjuvanted vaccine  was
      associated with an increased incidence of local (crude odds ratio [cOR], 1.56;
      95%  confidence interval [CI], 1.11-2.29) and systemic adverse events (cOR, 1.64;
      95% CI, 1.29-2.07)  after vaccination. Atopic dermatitis (adjusted OR [aOR],
      2.32; 95% CI, 0.99-5.46) might be the  choice risk factor for local adverse
      events, and adjuvant use (aOR, 1.35; 95% CI, 1.03-1.78)  was a significant
      predictor of systemic adverse events in healthy young male Korean soldiers.

PMID- 22627299
TI  - Serotype, Shiga toxin (Stx) type, and antimicrobial resistance of Stx-producing
      Escherichia coli isolated from humans in Shizuoka Prefecture, Japan (2003-2007).
AB  - The serotype, Shiga toxin (Stx) type, and antimicrobial resistance patterns of 
      138 Stx-producing Escherichia coli (STEC) strains isolated from humans between
      2003 and 2007 in  Shizuoka Prefecture, Japan were characterized. The predominant
      O serogroups of the STEC isolates  were O157, O26, and O111. Antimicrobial
      susceptibility testing of the STEC isolates showed that  31 of the 138 isolates
      (22.5%) were resistant to antibiotics. Compared to the results reported  in the
      previous studies, a higher rate of STEC O157 isolates were susceptible to all the
      antimicrobial agents used in this study. However, antimicrobial susceptibility
      data from this  study showed that antimicrobial resistance patterns have
      increased by 6 compared to the survey  performed by Masuda et al. between 1987
      and 2002 (Jpn. J. Food Microbiol., 21, 44-51, 2004).  This indicates that STEC
      isolates have evolved to show a variety of antimicrobial resistance  patterns. It
      is important to consider the population of isolates showing decreased 
      susceptibility to clinically relevant drugs such as ciprofloxacin (CPFX) and
      fosfomycin (FOM).  All the 3 STEC isolates resistant to nalidixic acid showed low
      susceptibility to CPFX (MIC,  0.25-0.5 MUg/ml). In addition, a decreased
      susceptibility to FOM was clearly observed in the  E. coli O26 isolates. Our
      findings also showed that 1 STEC O26 strain could possibly be a  chromosomal AmpC
      beta-lactamase hyperproducer. These results suggest that antimicrobial therapy 
      may be less effective in patients with non-O157 STEC infections than in those
      with STEC O157  infections.

PMID- 22627300
TI  - Isolation and identification of Escherichia albertii from a patient in an
      outbreak of gastroenteritis.
AB  - A microbial strain harboring the eae gene, which is known as the virulence gene 
      of enteropathogenic Escherichia coli (EPEC) and most enterohemorrhagic E. coli,
      was isolated  from a patient in a gastroenteritis outbreak that occurred in 22
      patients in Akita Prefecture,  Japan, in November 2011. The biochemical
      characteristics of the isolate were more similar to  those of a novel Escherichia
      sp., E. albertii than E. coli. Partial 16S rRNA gene sequences of  the isolate
      were identical to those of a certain E. albertii strain, but also showed a high 
      degree of similarity to those of E. coli strains. Finally, we identified this
      isolate as E.  albertii by performing PCR analysis that targeted the uidA, lysP,
      mdh, and cdtB genes  in addition to stx and eae genes to differentiate between
      the EPEC and E. albertii strains.

PMID- 22627301
TI  - A prospective comparison of the epidemiological and clinical characteristics of
      pandemic (H1N1) 2009 influenza A virus and seasonal influenza A viruses in
      Guangzhou, South China in 2009.
AB  - Comparisons of the clinical characteristics of contemporaneous pandemic (H1N1) 
      2009 influenza A virus (A(H1N1)pdm09)- and seasonal influenza viruses-infected
      patients are  important for both clinical management and epidemiological studies.
      A prospective multicenter  observational study was conducted using a
      preestablished sentinel surveillance system in  Guangzhou, China during 2009. In
      this study, the clinical presentations of patients with either  acute respiratory
      infection or community-acquired pneumonia were recorded, and nasopharyngeal  swab
      samples were collected for detection of respiratory virus strains using cell
      cultures or  real-time reverse transcription/real-time polymerase chain reaction.
      Comparisons of the  clinical features between A(H1N1)pdm09- and seasonal
      influenza viruses-infected patients were  conducted accordingly. Of the 1,498
      patients examined, 265 tested positive for A(H1N1)pdm09,  286 were positive for
      seasonal influenza A viruses, and 137 for influenza B viruses. The  predominant
      virus was influenza B before the emergence of A(H1N1)pdm09 (epidemiological week 
      [EW] 1-EW 21); then, predominantly non-A(H1N1)pdm09 influenza A and, later,
      A(H1N1)pdm09, which  peaked in EW 46. Compared with the common seasonal influenza
      infected patients,  A(H1N1)pdm09-infected patients were younger, and had a higher
      proportion of these patients  reported prior contact with infected individuals (P
      < 0.001, by chi(2) test). However, few  significant differences were observed in
      clinical symptoms and severity among any of the  infections caused by the
      different influenza A strains. Our hospital-based network served as a  useful
      source of information during A(H1N1)pdm09 monitoring. Viral distribution in
      Guangzhou was  characterized by a sharp rise in A(H1N1)pdm09-infected patients in
      September 2009. Similar to  seasonal influenza A-infected cases, A(H1N1)pdm09
      cases had a very small proportion of severe  cases.

PMID- 22627302
TI  - Distribution of mosquitoes and mosquito-borne viruses along the China-Myanmar
      border in Yunnan Province.
AB  - A total of 54,673 mosquitoes were collected at 11 sites located near the  China
      Myanmar border in the western part of Yunnan Province during July and August
      2007.  There were 29 species in 4 genera identified from the collections,
      including 12 species of  Culex, 12 species of Anopheles, 3 species of Aedes, and
      2 species of Armigeres. Culex  tritaeniorhynchus Giles (67.9%, 37,119/54,673) and
      Anopheles sinensis Wiedemann (25.9%,  14,170/54,673) were the most abundant
      species in this investigation. Virus was isolated using  BHK-21 and C6/36 cells
      from 22 of 510 mosquito pools. Isolates included Japanese encephalitis  virus
      (JEV) and Getah virus (GETV), which were identified by serological and molecular
      methods.  Twenty JEV strains were isolated from Cx. tritaeniorhynchus (15
      isolates), An. sinensis (3  isolates), and Armigeres subalbatus Coquillett (2
      isolates), and 2 GETV strains were isolated  from Culex pseudovishnui Colless and
      Cx. tritaeniorhynchus. This study suggests that Ar.  subalbatus is a potentially
      important local vector because of the high JEV infection ratio  found in this
      species. Enzootic JEV transmission persists in this area and therefore, 
      surveillance for human disease caused by JEV and GETV should be conducted in the
      region.

PMID- 22627303
TI  - Cost-benefit analysis of the tsutsugamushi disease prevention program in South
      Korea.
AB  - The purpose of this research was to evaluate the economic value of the 
      tsutsugamushi disease prevention program and to suggest whether to abolish or
      expand this  program. A cost-benefit analysis was conducted to evaluate the
      economic feasibility of this  prevention program. We collected cost data from 25
      public health centers (PHCs) and the medical  insurance data for all
      tsutsugamushi patients. We estimated the costs and benefits of the  program using
      a macro-costing method. The estimated total cost was $1.22 million with a 
      governmental cost of $697,000 and a cost of $521,000 to the PHCs. After the
      prevention program  was implemented, $581 were salvaged from medical costs, $46
      from non-medical costs, and $847  from productivity loss due to the reduced
      number of patients, with an estimated $6.66 million  per year in total benefits
      of the program. The ratio of benefit to cost was found to be 5.5,  making the
      economic value of the program significant. The net benefit should increase if the
      tsutsugamushi disease prevention program is continued and the implementation
      period is expanded  to 10 years.

PMID- 22627304
TI  - A comparative analysis of meropenem and doripenem in febrile patients with
      hematologic malignancies: a single-center retrospective study.
AB  - Many patients with hematologic malignancies show immunosuppression and/or
      neutropenia,  and are at a high risk of developing a serious infection that would
      require empiric therapy  with broad-spectrum antibiotics. However, a thorough
      comparison of the efficacies of different  carbapenems has not been carried out.
      To compare the efficacies of meropenem (MEPM) and  doripenem (DRPM) in febrile
      patients with hematologic neoplasms, we retrospectively reviewed  data of 149
      consecutive febrile patients with acute myeloid leukemia, acute lymphoblastic 
      leukemia, or myelodysplastic syndrome (MDS) who were treated empirically with
      MEPM or DRPM. The  duration from the start of carbapenem administration to
      decline of fever was not significantly  different between the MEPM and DRPM
      groups (median, 3 versus 4 days; P = 0.79). Multivariate  analysis showed that a
      diagnosis of MDS and the use of liposomal amphotericin-B or voriconazole  are
      statistically significant risk factors for sustained fever. In conclusion, MEPM
      and DRPM  showed similar efficacies in febrile patients with acute leukemia and
      MDS.

PMID- 22627305
TI  - Molecular epidemiology of a major subgroup of Arthroderma benhamiae isolated in
      Japan by restriction fragment length polymorphism analysis of the non-transcribed
      spacer region of ribosomal RNA gene.
AB  - Arthroderma benhamiae vectored by small animals, such as household pets, causes 
      tinea lesions on human skin. The number of tinea cases caused by this species is
      increasing in  Japan. We attempted to develop a simple molecular method for
      strain discrimination, which is  expected to be useful in molecular epidemiology.
      Out of the 61 strains of A. benhamiae  registered at our institute, 46 A.
      benhamiae strains showed very high degrees of sequence  similarity on cluster
      analysis of the internal transcribed spacer regions of ribosomal RNA  (rRNA)
      genes. These 46 strains, including 22 strains isolated from Japan, were further
      used for  strain typing by analyzing the non-transcribed spacer (NTS) region of
      the rRNA gene. Polymerase  chain reaction was performed using a primer pair
      designed for amplification of a part of the  NTS region, and the amplicons were
      successfully discriminated by restriction fragment length  polymorphism (RFLP)
      analysis performed using MvaI. RFLP analysis showed 11 NTS types  (NTS1-NTS11)
      among the 46 strains. Out of the 22 Japanese strains, 10 were of the NTS8 type; 
      6, of the NTS1 type; 3, of the NTS2 type; and 3, of the NTS5 type. Molecular
      typing showed  consistency of NTS types among the strains isolated from different
      lesions on the same patient,  among the strains derived from the same family, and
      among the strains from pets and their  owners. We observed that 3 out of the 4
      NTS types among the Japanese strains were detected  outside Japan as well.

PMID- 22627306
TI  - In vitro activity of linezolid against clinical isolates of Mycobacterium
      tuberculosis, including multidrug-resistant and extensively drug-resistant
      strains from Beijing, China.
AB  - The in vitro activity of linezolid was evaluated against 84 clinical isolates of 
      Mycobacterium tuberculosis, including multidrug-resistant (MDR) and extensively
      drug-resistant  (XDR) strains, isolated from the center for tuberculosis research
      and treatment of the Chinese  army. Linezolid showed excellent activity, with
      minimum inhibitory concentrations (MICs) of  0.125-0.5 MUg/mL against all tested
      isolates. There were no differences in the MIC(50) and MIC(90)  of linezolid
      between susceptible, isoniazid-resistant, MDR, and XDR. Indeed, all of the groups
      displayed identical MIC(90) values of 0.25 MUg/mL, which is lower than
      previously reported in  similar studies. We conclude that linezolid may be a more
      effective drug against M. tuberculosis  and may play an important role in
      treating drug-resistant tuberculosis in China.

PMID- 22627307
TI  - Preliminary evaluation of insecticide-impregnated ceiling nets with coarse mesh
      size as a barrier against the invasion of malaria vectors.
AB  - We evaluated the effectiveness of installing the Olyset(r) Net on the ceiling  in
      preventing the invasion of malaria vectors. This study was conducted in houses in
      western  Kenya. The number of resting mosquitoes inside the houses reduced when
      the ceiling and eaves of  the houses were covered with the net. The mosquito
      densities remained low for 9 months, until  the nets were removed.

PMID- 22627308
TI  - A rapid loop-mediated isothermal amplification assay targeting hspX for the
      detection of Mycobacterium tuberculosis complex.
AB  - A rapid, simple, and low-cost diagnostic tool for tuberculosis (TB) detection is 
      urgently needed in countries with a high TB burden. Here, we report a novel loop
      mediated  isothermal amplification (LAMP) assay targeting the hspX gene for the
      rapid detection of  Mycobacterium tuberculosis, M. bovis, M. africanum, and M.
      microti. The specificity of this  assay was evaluated using 4 reference strains
      of Mycobacterium tuberculosis complex (MTC), 22  species of non-tuberculous
      mycobacteria (NTM), 7 non-mycobacterial species, and 50 clinical  M. tuberculosis
      isolates. All the reference MTC strains and M. tuberculosis clinical isolates 
      were successfully detected by this method, and there were no false-positive
      results with NTM or  non-mycobacterial species, which demonstrates the high
      specificity of this assay for MTC. The  detection limit was 10 copies of MTC
      genome within 27 min, and the detection speed of this  assay was higher than that
      of any other isothermal methods reported so far. Because of its  speed,
      simplicity, sensitivity, specificity, and inexpensiveness, the TB hspX LAMP assay
      is a  potential gene diagnostic method for TB detection in developing countries
      with a high TB burden.

PMID- 22627309
TI  - Evaluation of transferability of R-plasmid in bacteriocin-producing donors to
      bacteriocin-resistant recipients.
AB  - Bacteriocin-producing Escherichia coli (donors) rapidly kill conventional 
      recipient E. coli DH5alpha in conjugation experiments. To evaluate plasmid
      transferability of  bacteriocin-producing donors, we established 2 different
      bacteriocin-resistant mutants derived  from E. coli DH5alpha and used them as
      recipients. When the bacteriocin-resistant mutants were  used in conjugation
      experiments, the transconjugant recovery from 20 bacteriocin-producing  donors
      increased from 5% (1/20) to 65% (13/20), and the transfer frequencies increased.
      These  results showed that bacteriocins inhibited the transfer of the R-plasmid
      from  bacteriocin-producing donors. Thus, application of bacteriocin-resistant
      recipients might aid  the evaluation of the potential transferability of plasmids
      from bacteriocin-producing donors.

PMID- 22627310
TI  - First report of class 1 and class 2 integrons in multidrug-resistant Klebsiella
      pneumoniae isolates from northwest Iran.
AB  - We investigated the prevalence of multidrug resistance, production of  extended
      spectrum beta-lactamases (ESBLs), and presence of class 1 and 2 integrons in 150 
      clinical isolates of Klebsiella pneumoniae from northwest Iran by performing
      phenotypic  confirmatory tests and polymerase chain reaction (PCR) analysis. Of
      the 150 isolates, 149  (99.3%) were multidrug resistant (MDR). Of the MDR
      isolates, 124 (83.2%) were ESBL positive.  The results of the PCR analysis showed
      that 117 (78.5%) and 20 (13.4%) MDR K. pneumoniae  isolates carried intI1 and
      intI2, respectively, and 16 (10.7%) MDR K. pneumoniae isolates  contained the
      integrase genes of both class 1 and class 2. Resistance of the isolates to 
      gentamicin, tetracycline, ceftazidime, cephalothin, chloramphenicol, and
      nalidixic acid was  observed to be significantly associated with the presence of
      class 1 integrons; however, the  resistance to tetracycline was observed to be
      associated with the presence of class 2 integrons  alone. This study showed that
      integrons are widely prevalent in the clinical isolates of  K. pneumoniae from
      northwest Iran, and that they may be playing an important role in  attributing
      multidrug resistance to the clinical K. pneumoniae isolates. To the best of our 
      knowledge, this is the first report showing the presence of class 1 and class 2
      integrons  in MDR K. pneumoniae isolates from clinical settings in northwest
      Iran.

PMID- 22627311
TI  - A molecular epidemiologic study of human adenovirus type 8 isolates causing
      epidemic keratoconjunctivitis in Kawasaki City, Japan in 2011.
AB  - A local outbreak of epidemic keratoconjunctivitis (EKC) caused by human 
      adenovirus type 8 (HAdV-D8) occurred in Kawasaki city, Japan in July-August 2011.
      Since the  cases were sporadic in nature, the source of the infection could not
      be identified. The results  of PCR analysis and the appearance of cytopathic
      effects in the samples indicated that 22  patients were positive for HAdV. The
      mean age of the patients (10 men and 12 women) was 64.3  +/- 17.3 years (median,
      68 years; range, 11-86 years). The sequences of hexon, which included 
      hypervariable loop 1; the penton, which included RGD loops; and the fiber, which
      included the  knob-coding regions, were identical in all the HAdV-positive cases.
      Phylogenetic analysis of  the major capsid protein-encoding regions of HAdV
      confirmed that the isolates were HAdV-D8.  Although the incidence of HAdV-D8
      outbreaks has decreased in Japan since 1997, the results of  our study imply that
      HAdV-D8 is still a causative agent for EKC outbreaks in Japan.

PMID- 22627312
TI  - Antibiotic susceptibility pattern and the indicator of decreased ciprofloxacin
      susceptibility of Salmonella enterica serovar Typhi isolated from Dhulikhel
      Hospital, Nepal.
AB  - Monitoring the antibiotic susceptibility pattern of Salmonella enterica serovar
      Typhi  (S. Typhi) is important for efficiently managing cases of typhoid fever.
      In this study,  the antimicrobial susceptibility patterns of 114 S. Typhi
      isolates, which were collected from  a university hospital in Nepal during July
      2009-December 2010, were investigated by disc  diffusion assays. All of the S.
      Typhi isolates were sensitive to amoxycillin-clavulanic acid.  More than 95% of
      the isolates were sensitive to chloramphenicol, ceftazidime, ceftriaxone, and 
      cotrimoxazole. In addition, 1.7% of the studied isolates showed multiple drug
      resistance  patterns. Of the 40 S. Typhi isolates, 32 strains (80%) showed
      nalidixic acid (NA) resistance  with decreased susceptibility to ciprofloxacin
      (CIP). Importantly, we found the simultaneous  presence of NA resistance and
      decreased susceptibility to CIP, suggesting that the resistance  to NA is a
      reliable indicator of decreased CIP susceptibility (sensitivity, 97.5%;
      specificity,  100.0%). Furthermore, the sequencing of NA-resistant S. Typhi
      isolates showed a predominant  amino acid alteration in the quinolone resistance
      determining region (QRDR) of gyrA gene at  position 83 from Ser->Phe. Two
      isolates with resistance to both CIP and NA had a  double-mutation (Ser83->Phe
      and Asp87->Asn) in the QRDR of the gyrA gene, of which one had an  additional
      amino acid mutation (Ser80->Ilu) in the QRDR of the parC gene.

PMID- 22627313
TI  - Imported cases of measles in Niigata, Japan in 2011.

PMID- 22627314
TI  - Detection of human coronavirus NL63 and OC43 in children with acute respiratory
      infections in Niigata, Japan, between 2010 and 2011.

PMID- 22627315
TI  - A case of urethritis caused by human adenovirus type 56.

PMID- 22627316
TI  - Vertical transmission of dengue virus in Aedes aegypti collected in Surabaya,
      Indonesia, during 2008-2011.

PMID- 22627317
TI  - Shigella sonnei outbreak among men who have sex with men in Tokyo.

PMID- 22627318
TI  - Zwitterionic half-sandwich Rh and Ir complexes containing a diphosphine nido
      carborane ligand: synthesis, structure transformation and application in H2
      activation.
AB  - Several novel zwitterionic half-sandwich complexes and pseudocloso
      metallacarboranes based on 1,2-(PPh(2))(2)-1,2-C(2)B(10)H(10) were successfully
      prepared, and further study proved that some of them can activate H(2) to form
      the metal hydride complexes Cp*M(H)(7,8-(PPh(2))(2)-7,8-C(2)B(9)H(10)) (M = Rh,
      Ir).

PMID- 22627319
TI  - High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome
      for standard chemotherapy in acute myeloid leukaemia.
AB  - BACKGROUND: Cytosine arabinoside-based chemotherapy coupled with anthracycline is
      currently the first-line treatment for acute myeloid leukaemia (AML), but diverse
      responses to the regimen constitute obstacles to successful treatment. Therefore,
      outcome prediction to chemotherapy at diagnosis is believed to be a critical
      consideration. METHODS: The mRNA expression of 12 genes closely involved in the
      actions of cytosine arabinoside and anthracycline was evaluated by real-time
      reverse transcriptase PCR (RT-PCR), in 54 diagnostic bone marrow specimens of M2
      subtype AML. RESULTS: Low expression levels of ribonucleotide reductase M2 (RRM2)
      and high expression levels of topoisomerase 2 beta (TOP2B) were correlated with
      longer survival in a univariate analysis. Another interesting finding is that
      high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis
      were also shown to have a prognostic impact for longer survival with improved
      accuracy. Among the four markers, when adjusted for the influence of other
      clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was
      significantly correlated with treatment outcomes; patients with high ratios
      trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall
      survival (HR, 0.29; P=0.005). CONCLUSION: Genes with distinct expression profiles
      such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome
      prediction after the treatment with standard regimens in AML patients with M2
      subtype.

PMID- 22627323
TI  - Politicizing women's choices--again.
AB  - Why the commotion over Planned Parenthood and Ann Romney matters.

PMID- 22627322
TI  - Model testing, prediction and experimental protocols in neuroscience: a case
      study.
AB  - In their theoretical and experimental reflections on the capacities and
      behaviours of living systems, neuroscientists often formulate generalizations
      about the behaviour of neural circuits. These generalizations are highly
      idealized, as they omit reference to the myriads of conditions that could perturb
      the behaviour of the modelled system in real-world settings. This article
      analyses an experimental investigation of the behaviour of place cells in the rat
      hippocampus, in which highly idealized generalizations were tested by comparing
      predictions flowing from them with real-world experimental results. The aim of
      the article is to identify (1) under what conditions even single prediction
      failures regarding the behaviour of single cells sufficed to reject highly
      idealized generalizations, and (2) under what conditions prima facie counter
      examples were deemed to be irrelevant to the testing of highly idealized
      generalizations. The results of this analysis may contribute to understanding how
      idealized models are tested experimentally in neuroscience and used to make
      reliable predictions concerning living systems in real-world settings.

PMID- 22627320
TI  - Targeting heat shock protein 27 (HspB1) interferes with bone metastasis and
      tumour formation in vivo.
AB  - BACKGROUND: The small stress heat shock protein 27 (Hsp27) has recently turned as
      a promising target for cancer treatment. Hsp27 upregulation is associated with
      tumour growth and resistance to chemo- and radio-therapeutic treatments, and
      several ongoing drugs inhibiting Hsp27 expression are under clinical trial. Hsp27
      is now well described to counteract apoptosis and its elevated expression is
      associated with increased aggressiveness of several primary tumours. However, its
      role in the later stage of tumour progression and, more specifically, in the
      later and most deadly stage of tumour metastasis is still unclear.
      METHODS/RESULTS: In the present study, we showed by qRT-PCR that Hsp27 gene is
      overexpressed in a large fraction of the metastatic breast cancer area in 53
      patients. We further analysed the role of this protein in mice during bone
      metastasis invasion and establishment by using Hsp27 genetically depleted MDA
      MB231/B02 human breast cancer cell line as a model. We demonstrate that Hsp27
      silencing led to reduced cell migration and invasion in vitro and that in vivo it
      correlated with a decreased ability of breast cancer cells to metastasise and
      grow in the skeleton. CONCLUSION: Altogether, these data characterised Hsp27 as a
      potent therapeutic target in breast cancer bone metastasis and skeletal tumour
      growth.

PMID- 22627324
TI  - Let teens provide their own consent for the HPV vaccine.
AB  - The evidence says it doesn't increase sexual activity or cause intellectual
      disabilities, but it will save lives.

PMID- 22627325
TI  - Meds in the pea soup.

PMID- 22627326
TI  - A seat on the board.

PMID- 22627327
TI  - Delegating school nursing.

PMID- 22627328
TI  - Postoperative abortion care.

PMID- 22627329
TI  - Effectiveness of nondrug pain relief during labor.
AB  - A review calls for more trials on techniques that have only empirical support.

PMID- 22627330
TI  - Nurse-initiated corticosteroids for pediatric asthma in the ED.
AB  - Hospital admission rates were lower and time to ED discharge was shorter.

PMID- 22627332
TI  - Fighting obesity, locally and nationally.
AB  - Fifty regional teams participate in Collaborate for Healthy Weight.

PMID- 22627336
TI  - Breast milk sharing is making a comeback, but should it?
AB  - Internet access provides convenience but carries real risks.

PMID- 22627339
TI  - Does treatment of periodontal disease improve glycemic control in diabetes?
AB  - Editor's note: This is the eighth in a series of summaries of nursing care-
      related systematic reviews from the Cochrane Library.

PMID- 22627340
TI  - You're being investigated by your state nursing board.
AB  - What to do when the nursing board investigates or takes action against you.

PMID- 22627347
TI  - Interdisciplinary team training:  five lessons learned.
AB  - Communication and teamwork improved on this labor and delivery unit.

PMID- 22627353
TI  - The journey to magnet:  an international perspective.
AB  - An Australian hospital achieves recognition by the ANCC's Magnet program.

PMID- 22627354
TI  - The safe use of negative-pressure wound therapy.
AB  - The Pennsylvania Patient Safety Reporting System is a confidential, statewide
      Internet reporting system to which all Pennsylvania hospitals, outpatient-surgery
      facilities, and birthing centers, as well as some abortion facilities, must file
      information on medical errors. Safety Monitor is a column from Pennsylvania's
      Patient Safety Authority, the authority that informs nurses on issues that can
      affect patient safety and presents strategies they can easily integrate into
      practice. For more information on the authority, visit
      www.patientsafetyauthority.org. For the original article discussed in this column
      or for other articles on patient safety, click on "Patient Safety Advisories" and
      then "Advisory Library" in the left-hand navigation menu.

PMID- 22627355
TI  - Promoting community health.
AB  - A nurse-managed health center bridges the gap to care.

PMID- 22627356
TI  - Dangers of the menopause. 1910.
AB  - Editor's note: From its first issue in 1900 through to the present day, AJN has
      unparalleled archives detailing nurses' work and lives over the last century.
      These articles not only chronicle nursing's growth as a profession within the
      context of the events of the day, but they also reveal prevailing societal
      attitudes about women, health care, and human rights. Today's nursing school
      curricula rarely include nursing's history, but it's a history worth knowing. To
      this end, From the AJN Archives will be a frequent column, containing articles
      selected to fit today's topics and times.This month's article, from the September
      1910 issue, is "Dangers of the Menopause." The author, Anne E. Perkins, MD,
      states that its purpose is to correct "popular fallacies," so nurses can
      "disseminate knowledge of the real dangers" of menopause. It's interesting how
      much information in the article is still valid 100 years later, such as the need
      to investigate any postmenopausal bleeding. It's also noteworthy that the three
      symptoms causing women the most distress-hot flashes, insomnia, and mood problems
      haven't changed, although a comparison of Dr. Perkins's article with "Managing
      Menopausal Symptoms" in this issue reveals that menopause management certainly
      has: from a "trip abroad" and avoiding "fancy work" in 1910 to physical exercise
      and acupuncture in 2012. To read the complete article from our archives, go to
      http://bit.ly/IZkCiD.

PMID- 22627357
TI  - Seized.
AB  - A child's chronic illness may be impossible to control, but there's still a
      choice to make.

PMID- 22627358
TI  - Eosinophils are now recognized to play a role in health and disease, with a
      functional diversity due to multifaceted biological properties. Preface.

PMID- 22627359
TI  - Pathophysiologic role of histamine: evidence clarified by histidine decarboxylase
      gene knockout mice.
AB  - The role of histamine in various murine disease models has been clarified using
      histidine decarboxylase gene knockout mice. The mice were generated using
      conventional gene-targeting methods. Studies, including ours, using knockout mice
      have shown that the activity of histamine is not limited to allergic, peptic and
      neurologic functions as in the old paradigm, but extends to other processes
      related to wound healing, circulatory disease, immunology, oncology and
      infectious disease. The recent observation of the activity of newly cloned
      histamine receptors and a pathophysiologic effect of histamine has dramatically
      expanded our understanding of the scope of histamine function.

PMID- 22627360
TI  - Murine T cell-derived contractile activity for bronchial smooth muscle cells.
AB  - BACKGROUND: Adoptive transfer of helper T (Th) cells conferred a late asthmatic
      response upon antigen challenge. A possible production of a contractile activity
      for bronchial smooth muscle (BSM) by activated Th cells was examined. METHOD:
      Murine Th clones were stimulated with immobilized anti-CD3 antibody in the
      presence or absence of anti-CD28 antibody. Culture supernatants were dialyzed and
      then applied to the collagen gels containing cultured human BSM cells. RESULTS:
      Culture supernatants of activated but not resting murine Th clones that conferred
      a late asthmatic response, induced the contraction of human BSM cell-containing
      collagen gels. CONCLUSION: Activated Th cells produce a contractile activity for
      BSM in vitro.

PMID- 22627361
TI  - Eosinophil granular proteins damage bronchial epithelial cells infected with
      respiratory syncytial virus.
AB  - BACKGROUND: Respiratory syncytial (RS) virus infection is an important
      exacerbating factor in acute bronchial asthma. However, the precise mechanisms
      responsible for viral infection-induced exacerbations of asthma are uncertain. To
      elucidate the role of eosinophilic inflammation in the pathogenesis of virus
      induced asthma, we investigated the effects of eosinophil granule proteins on
      bronchial epithelial cell infected with RS virus. METHODS: Morphological changes
      and cytopathic effects in human type II pulmonary alveolar epithelial cells
      (A549) infected with RS virus and/or eosinophil granule proteins such as major
      basic protein (MBP), eosinophil peroxidase (EPO), eosinophil cationic protein
      (ECP) and eosinophil-derived neurotoxin (EDN) were observed by microscopy.
      Apoptosis/necrosis was evaluated by trypan blue exclusion test. We also measured
      8 types of phosphorylated proteins in MBP-treated A549 cells infected with RS
      virus. RESULTS: Although RS virus alone did not affect the cytopathic effects of
      A549 cells, high concentrations of MBP or a combination of 4 granule proteins
      resulted in cytopathic effects. MBP or EPO, but not ECP or EDN, induced
      cytotoxicity and necrosis of the infected A549 cells. Furthermore, MBP induced
      the phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2, p38
      mitogen-activated protein kinase (MAPK), Jun-N-terminal protein kinase (JNK), and
      signal transducer and activator of transcription (STAT)3 in the infected cells.
      CONCLUSIONS: These results suggest that eosinophil granule proteins, specifically
      MBP, damage bronchial epithelial cells infected with RS virus and that the MAPK
      family are involved in these responses, indicating that eosinophilic inflammation
      might be associated with the pathophysiology of RS virus-induced acute
      exacerbations of asthma.

PMID- 22627363
TI  - NFAT1 and NFAT2 differentially regulate IL-17A expression in human T cells.
AB  - BACKGROUND: The NFAT family transcription factors play crucial roles in T cell
      functions. Recently, NFAT has been implicated in the production of an
      inflammatory cytokine, IL-17A; however, functional differences among NFAT members
      in IL-17A synthesis have not been elucidated. In this study, the relative
      contribution of NFAT1 and NFAT2 to IL-17A expression in human T cells was
      investigated. METHODS: NFAT1 and NFAT2 were introduced in human cord blood CD4+ T
      cells by a lentiviral transduction system. Then, the expression of IL-17A mRNA
      was determined by quantitative real-time RT-PCR. The transient effects of NFAT1
      and NFAT2 on IL-17A expression in Jurkat-Tag cells were also investigated.
      RESULTS: Stimulation-induced expression of IL-17A in human CD4+ T cells was
      augmented by the introduction of NFAT1 and more vigorously, NFAT2. IL-17A
      expression in Jurkat-Tag cells was also enhanced by NFAT1, whereas it was not
      affected by NFAT2. CONCLUSION: NFAT1 and NFAT2 facilitated IL-17A expression in
      human T cells, though distinct mechanisms might be involved in these effects.

PMID- 22627362
TI  - Alternaria fungus induces the production of GM-CSF, interleukin-6 and interleukin
      8 and calcium signaling in human airway epithelium through protease-activated
      receptor 2.
AB  - RATIONALE: Recent studies suggest that host immune responses to environmental
      fungi may play an important role in the development of allergic diseases, such as
      human asthma. Epithelium is considered an active participant in allergic
      inflammation. We previously reported that aspartate protease from Alternaria
      induces the activation and degranulation of human eosinophils that are mediated
      through protease-activated receptor 2 (PAR-2). However, our current knowledge on
      the innate immune responses of epithelium to environmental fungi is very limited.
      We investigated the responses of epithelium to fungi and the mechanisms of these
      responses. METHODS: Human airway epithelial cell line BEAS-2B and Calu-3 (both
      from American Type Culture Collection) were incubated with PAR-2 peptides and
      extracts of various fungi. The cellular responses, including GM-CSF, interleukin
      (IL)-6, IL-8, eotaxin, eotaxin-2 and RANTES production as well as increases in
      intracellular calcium concentration ([Ca(2+)](i)), were examined. To characterize
      the proteases involved in these responses, protease inhibitors such as pepstatin
      A and alkalo-thermophilic Bacillus inhibitor (ATBI), HIV protease inhibitors and
      4-amidinophenylmethanesulfonyl fluoride hydrochloride were used. To investigate
      the role of PAR-2, PAR-2-agonistic and PAR-2-antagonistic peptides were used.
      RESULTS: PAR-2-activating peptide, but not the control peptide, induced GM-CSF,
      IL-6 and IL-8 production; these cellular responses were accompanied by a quick
      and marked increase in [Ca(2+)](i). Among 7 common environmental fungi, only
      Alternaria induced GM-CSF, IL-6 and IL-8 production and increased [Ca(2+)](i)
      response. Both cytokine production and increased [Ca(2+)](i) were significantly
      inhibited by PAR-2 antagonist peptide and by aspartate protease inhibitors
      (pepstatin A, ritonavir, nelfinavir and ATBI), but not by the PAR-2 control
      peptide or by other protease inhibitors. CONCLUSIONS: Aspartate proteases from
      Alternaria induce cytokine production and calcium response in airway epithelium
      that is mediated through PAR-2. This protease-mediated activation of airway
      epithelium may be implicated in the development and exacerbation of airway
      allergic disease.

PMID- 22627364
TI  - Higher sensitivity of male CD4+ T cells to suppressive effects of CD8+ T cells on
      IL-5 production compared to female CD4+ T cells.
AB  - BACKGROUND: Asthma prevalence and severity are higher in females than in males
      after puberty. The underlying mechanisms of this gender difference are not fully
      understood. More severe airway inflammation in female mice has been reported to
      be associated with higher levels of T helper type 2 (Th2) cytokines in asthma
      models. The aim of this study was to investigate sex differences in CD4+ and CD8+
      T cell functions in Th2 cytokine production. METHODS: Splenocytes from naive mice
      were stimulated with anti-CD3/CD28 antibodies and the proportions of CD4+ and
      CD8+ T cells were analyzed. CD4+ T cells were stimulated in the presence of CD8+
      T cells. The concentrations of interleukin (IL)-5, IL-10 and interferon (IFN)
      gamma in the cultures were measured. RESULTS: The concentration of IL-5, but not
      IFN-gamma, was significantly higher in female splenocytes than in male
      splenocytes. There were no sex differences in the proportions of CD4+ and CD8+ T
      cells in the splenocytes. Although the IL-5 production levels in male and female
      CD4+ T cells were similar, IL-5 production in male CD4+ T cells, but not female
      CD4+ T cells, was suppressed by both male and female CD8+ T cells. While IL-5 and
      IL-10 were not detected in the cultures from both male and female CD8+ T cells,
      IFN-gamma concentration in female CD8+ T cells was significantly higher than in
      male CD8+ T cells. CONCLUSIONS: The sex difference in the sensitivity of CD4+ T
      cells to CD8+ T cell suppression might contribute to the sex difference in IL-5
      production by splenocytes.

PMID- 22627365
TI  - Roles of CRTH2+ CD4+ T cells in immunoglobulin G4-related lacrimal gland
      enlargement.
AB  - BACKGROUND: Lacrimal gland enlargement (LGE) is one of the characteristics of
      Mikulicz's disease (MD). Recently, marked serum immunoglobulin (Ig)G4 elevation
      and infiltration of IgG4-positive plasma cells in the enlarged exocrine glands
      have been reported in MD patients. Moreover, we have reported that in patients
      with LGE and elevated serum IgG4 levels (IgG4-related LGE), T helper type 2 (Th2)
      cell-mediated immune responses are enhanced. Although prostaglandin D2 (PGD2) and
      its receptor CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2
      cells) have been shown to be involved in Th2 cell-related diseases such as
      bronchial asthma, their roles in IgG4-related diseases remain unknown. AIM: The
      aim of this study is to address the role of CD4+ T cells expressing CRTH2 (CRTH2+
      CD4+ T cells) in IgG4-related LGE. METHODS: We examined the expression of CCR4,
      CXCR3 and CRTH2 on peripheral blood CD4+ T cells in patients with IgG4-related
      LGE, in patients with bronchial asthma and in healthy controls. RESULTS: The
      ratio of CCR4+ to CXCR3+ in CD45RO+ CD4+ T cells was increased in patients with
      IgG4-related LGE when compared to that in healthy controls, confirming that Th2
      cells are predominant in patients with IgG4-related LGE. In addition, the
      frequency of CRTH2+ cells in CD4+ T cells was significantly increased in these
      patients, compared to healthy controls. Furthermore, although not statistically
      significant, the frequency of CRTH2+ cells in CD4+ T cells tended to correlate
      with the levels of serum IgE and the number of blood eosinophils in patients with
      IgG4-related LGE. CONCLUSION: CRTH2+ CD4+ T cells may be involved in the
      pathogenesis of IgG4-related LGE.

PMID- 22627366
TI  - Elevated levels of interleukin-33 in the nasal secretions of patients with
      allergic rhinitis.
AB  - BACKGROUND: Interleukin (IL)-33, which is a member of the IL-1 family of
      cytokines, is now recognized as an important contributor to Th2-type immune
      responses. We examined whether the levels of IL-33 in sera and nasal secretions
      are upregulated in allergic rhinitis (AR) patients, and we tested for
      correlations between the IL-33 level and the parameters of atopy and the nasal
      symptom score. METHODS: The study included 24 Japanese cedar pollinosis patients
      (12 male and 12 female patients with a mean age of 47.7 years) with a history of
      moderate-to-severe AR, 14 house-dust-mite-sensitized patients with AR (9 male and
      5 female patients with a mean age of 42 years) and 8 normal controls. We used
      Japan Rhinoconjunctivitis Quality-of-Life Questionnaire sheets to evaluate the
      nasal symptoms. We collected sera and nasal secretions to examine the level of IL
      33 protein by ELISA. RESULTS: IL-33 protein was not detected in the serum of any
      of the subjects. However, the IL-33 level in nasal secretions was significantly
      elevated in patients with Japanese cedar pollinosis at peak season and in
      patients with perennial AR compared to Japanese cedar pollinosis patients at
      preseason and the normal controls. Furthermore, IL-33 in nasal secretions
      correlated significantly with the total nasal symptom score. CONCLUSIONS: Our
      results suggest that IL-33 in nasal secretions may be related to exacerbation of
      AR, including that of Japanese cedar pollinosis cases.

PMID- 22627367
TI  - 1,25-Dihydroxyvitamin D3 upregulates functional C-x-C chemokine receptor type 4
      expression in human eosinophils.
AB  - BACKGROUND: Epidemiological studies suggest that vitamin D may be protective
      against the inception and exacerbation of allergic diseases. However, the direct
      effect of vitamin D on eosinophils, the major effector cells in allergic
      inflammation, is not known. It has been reported that C-X-C chemokine receptor
      type 4 (CXCR4) in eosinophils is induced in non-Th2 cytokine milieu or in
      response to glucocorticoids, recruiting the cell to noninflammatory sites.
      OBJECTIVES: To test whether 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3) or
      calcitriol], the active metabolite of vitamin D, acts directly on eosinophils to
      induce upregulation of CXCR4. METHODS: Peripheral blood eosinophils from normal
      volunteers were isolated by CD16 immunomagnetic beads. Vitamin D receptor (VDR)
      expression was detected by RT-PCR. Eosinophils were cultured with 1,25
      (OH)(2)D(3) and the survival and expression of CXCR4 on eosinophils were measured
      by flowcytometry. Eosinophil migration by CXCL-12/SDF-1 in the presence of 1,25
      (OH)(2)D(3) was also analyzed. RESULTS: Eosinophils expressed VDR. 1,25
      (OH)(2)D(3) prolonged eosinophil survival and upregulated eosinophil surface
      expression of CXCR4 in a concentration-dependent manner. Interleukin (IL)-5
      significantly reduced CXCR4 expression and migration induced by the ligand CXCL
      12/SDF-1. 1,25-(OH)(2)D(3) reversed the negative effects of IL-5 on the CXCR4
      CXCL12 pathway. CONCLUSION: 1,25-(OH)(2)D(3) regulates CXCR4 expression in
      eosinophils. The mechanism may be involved in eosinophil recruitment to
      noninflammatory sites where the ligand of CXCR4 is constitutively expressed.

PMID- 22627368
TI  - Possible regulatory role of galectin-9 on Ascaris suum-induced eosinophilic lung
      inflammation in mice.
AB  - BACKGROUND: Galectin-9 (Gal-9) is a member of the galectin family of lectins that
      exhibit binding affinity for beta-galactosides. We found a T cell line-derived
      Gal-9 with novel eosinophil chemoattractant activity, but its role in
      eosinophilic inflammation of the lung is unknown. We evaluated the role of Gal-9
      in Ascaris suum-induced eosinophilic lung inflammation in mice. METHODS: To
      evaluate the role of Gal-9 in Ascaris suum-induced eosinophilic lung
      inflammation, we developed a mouse model of eosinophilic pneumonia induced by the
      Ascaris suum antigen, and analyzed eosinophilic inflammation in Gal-9-deficient
      mice. The therapeutic effects of recombinant Gal-9 on lung inflammation were also
      examined in this mouse model. To evaluate lung inflammation, numbers of
      inflammatory cells and cytokine levels in the bronchoalveolar lavage fluid (BALF)
      were estimated by flow cytometry and enzyme-linked immunosorbent assay,
      respectively. RESULTS: The BALF of this mouse model of eosinophilic pneumonia
      induced by the Ascaris suum antigen contained increased numbers of inflammatory
      cells and elevated Gal-9 levels. Compared with wild-type mice, the BALF of Gal-9
      deficient mice contained higher numbers of both eosinophils and T helper type 2
      (Th2) cells. Th2 cytokines and eotaxin levels were also higher, and levels of
      CD4+CD25+Foxp3+ regulatory T cells were lower in Gal-9-deficient mice than in
      wild-type mice. Intranasal administration of recombinant Gal-9 prevented
      eosinophilic inflammation of the lung and upregulated the release of endogenous
      Gal-9. CONCLUSIONS: Our findings suggest that Gal-9 negatively regulates Th2
      mediated eosinophilic inflammation of the lung and that Foxp3+ regulatory T cells
      might be involved in suppressing allergic inflammation.

PMID- 22627369
TI  - Inhibition of allergen-induced airway inflammation by low-dose oral immunotherapy
      with transgenic rice seeds independently of immunoglobulin e synthesis.
AB  - BACKGROUND: Oral immunotherapy is potentially useful for the treatment of
      allergic diseases. We previously demonstrated that allergen-induced airway
      inflammation and immunoglobulin E (IgE) production in mice were suppressed by
      oral administration of high-dose transgenic (Tg) rice seeds (approximately 50
      g/kg/day) expressing a T cell epitope of Dermatophagoides pteronyssinus group 1
      allergen (Der p 1). However, this amount of Tg rice seeds was not realistic in
      our daily life. In this study, allergen-induced airway inflammation and IgE
      production following oral immunotherapy with a realistic (lowest) dose of Tg rice
      seeds were investigated. METHODS: Mice orally administered with Tg or non-Tg rice
      seeds at approximately 5 g/kg/day for 1 week were immunized with recombinant Der
      p 1, and then challenged with the corresponding allergen. The infiltration of
      inflammatory cells into the airways and the levels of allergen-specific serum IgE
      were examined. RESULTS: Low-dose oral administration of Tg rice seeds
      significantly inhibited the allergen-induced infiltration of eosinophils and
      lymphocytes into the airways, but allergen-specific IgE synthesis was not
      changed. CONCLUSIONS: Low-dose oral immunotherapy with Tg rice seeds could
      suppress allergen-induced airway inflammation through mechanisms other than the
      downregulation of IgE synthesis.

PMID- 22627370
TI  - Elevated numbers of cells producing interleukin-5 and interleukin-10 in a boy
      with Kimura disease.
AB  - Kimura disease is a rare disorder of unknown etiology, characterized by the
      presence of benign subcutaneous granuloma, marked peripheral blood eosinophilia
      and elevation of the immunglobulin E (IgE) serum level. Here, we present a case
      of a 12-year-old boy with Kimura disease who had a history of repeated severe
      influenza virus A infection. Along with the characteristic histological findings
      of granuloma, including eosinophil infiltration, enzyme-linked immunospot assay
      showed elevated numbers of IL-5- and IL-10-producing cells in the peripheral
      blood. Immunohistochemical evaluation, however, did not detect IL-5 in the
      tissue. Possible cytokine dysregulation in Kimura disease was suggested, but the
      pathogenesis remains unclear.

PMID- 22627371
TI  - Eosinophilic gastroenteritis due to cow's milk allergy presenting with acute
      pancreatitis.
AB  - Eosinophilic gastroenteritis (EGE) is characterized by eosinophilic infiltration
      of the digestive organs, most commonly of the stomach and the duodenum. Symptoms
      of EGE are nonspecific and include nausea, vomiting, abdominal pain, dyspepsia,
      malabsorption, ascites and weight loss. The various symptoms of EGE depend on its
      location and the depth of gastrointestinal eosinophil infiltration. We report a
      case presenting with acute pancreatitis caused by a milk allergy. The patient's
      symptoms rapidly improved after treatment with corticosteroids, and he remained
      symptom-free for more than 20 months by the elimination of cow's milk from his
      diet. Serum titers of pancreatic enzymes and total bilirubin simultaneously
      recovered and blood eosinophil counts normalized. The causative allergens of EGE
      are too various to detect; however, allergologic exams revealed that a cow's milk
      allergy had provoked EGE in our case. Adult-onset cow's milk allergies are rare;
      when seen, however, they may present severe complications such as anaphylaxis,
      gastroenteritis and pancreatitis. When unaccountable gastrointestinal symptoms
      are observed, EGE caused by food allergies should be included in the differential
      diagnosis.

PMID- 22627372
TI  - Eosinophilic gastrointestinal disorder in an infant with feeding dysfunction.
AB  - Feeding dysfunction (FD) has recently been considered to comprise a prevalent set
      of symptoms in eosinophilic gastrointestinal disorders (EGIDs) in young children.
      We report the case of an 8-month-old girl with an EGID who visited our hospital
      due to vomiting, poor weight gain and feeding difficulties; her condition was
      discovered during the examination of the symptoms including FD. Tracheal
      aspiration and reduced esophageal clearance showed up in a barium swallow test
      and upper gastrointestinal contrast radiography, respectively. Delayed clearance
      from the stomach was also detected on gastrointestinal scintigraphy.
      Gastrointestinal endoscopy and biopsies revealed esophagitis with some
      eosinophils and duodenitis with eosinophilic inflammation. She was not a likely
      candidate for eosinophilic esophagitis. On administration of an elemental diet,
      the patient gained weight. Esophageal and stomach clearance subsequently
      improved, although the vomiting and FD persisted to some extent. We conclude that
      it is important to consider other EGIDs as well as eosinophilic esophagitis in
      the differential diagnosis of FD.

PMID- 22627373
TI  - Obesity and eosinophilic inflammation: does leptin play a role.
AB  - It has been pointed out that obesity is a risk factor for, and is involved in the
      exacerbation of asthma. Mounting evidence about adipose tissue-derived proteins
      (adipokines) gave rise to the current understanding of obesity as a systemic
      inflammatory disorder. In this review, we summarized the involvement of leptin,
      focusing on eosinophil functions. Several studies have indicated that leptin can
      restrain eosinophil apoptosis, enhance migration, increase adhesion molecules and
      induce cytokine production. Since leptin also acts on a variety of immune cells
      related to allergic response, increased leptin in obese individuals potentially
      explains the mechanism by which obesity leads to an exacerbation of asthma.
      Further studies targeting adipokines will delineate the association between
      obesity and eosinophil-associated diseases.

PMID- 22627374
TI  - Critical roles of IKB kinase subunits in mast cell degranulation.
AB  - The IkappaB kinase (IKK) complex plays a crucial role in the activation of the
      transcription factor NF-kappaB by phosphorylating an inhibitory molecule
      IkappaBalpha. Recently, we showed that IKK2 (also called IKKbeta), a catalytic
      subunit of the IKK complex, induces immunoglobulin E-mediated degranulation in
      mast cells by phosphorylating SNAP-23, the target-membrane soluble N
      ethylmaleimide-sensitive fusion factor attachment protein receptor (SNARE). In
      addition to IKK2, a recent study has shown that ELKS, a regulatory subunit of the
      IKK complex, also induces the degranulation of rat basophilic leukemia cells.
      These findings indicate that the two subunits of the IKK complex, IKK2 and ELKS,
      function not only in NF-kappaB-dependent transcriptional activation but also in
      NF-kappaB-independent pathways. This review focuses on the functions of IKK2 and
      ELKS in mast cell degranulation.

PMID- 22627375
TI  - Neutrophilic inflammation in severe asthma.
AB  - Neutrophils may play an important role in the pathogenesis of severe asthma.
      Their infiltration into the airway is increased. Interleukin (IL)-8 is involved
      in this process, and is actually upregulated in the airways of patients. We have
      observed that in the absence of eosinophil chemoattractants, neutrophils
      stimulated by IL-8 augment eosinophil trans-basement membrane migration by
      releasing superoxide anion, matrix metalloproteinase, leukotriene B(4) and
      platelet-activating factor. These findings suggest that IL-8-stimulated
      neutrophils could lead eosinophils to accumulate in the airways of asthmatic
      patients, which might be a mechanism for corticosteroid resistance in severe
      asthma. However, the mechanisms of IL-8 upregulation in the airway are not
      completely understood. Several studies suggest that IL-17 (or T helper 17 cells;
      Th17) is involved in the IL-8 upregulation observed in severe asthma. We
      clarified that dopamine induces Th17 differentiation through dopamine D1-like
      receptor (D1-like-R), and that the D1-like-R antagonist attenuates Th17-mediated
      diseases like experimental autoimmune encephalomyelitis. Furthermore, we
      demonstrated that a D1-like-R antagonist significantly suppressed ovalbumin (OVA)
      induced neutrophilic airway inflammation in OVA T cell receptor-transgenic
      DO11.10 mice through inhibiting Th17-mediated immune responses. Therefore,
      dopamine D1-like-R antagonists could become useful for treating Th17-mediated
      neutrophil-dominant severe asthma. As inhaled corticosteroids are known to be
      less effective for controlling neutrophilic inflammation, a more effective
      therapeutic strategy for neutrophil-dominant asthma should still be elucidated.

PMID- 22627376
TI  - Effects of 30Hz theta burst transcranial magnetic stimulation on the primary
      motor cortex.
AB  - Theta Burst Stimulation (TBS) is a relatively new form of repetitive Transcranial
      Magnetic Stimulation (TMS) used to probe neuroplasticity in the human cortex.
      Thirty-Hz TBS, a variation of the originally described 50Hz TBS, has been shown
      to induce cortical changes in several nonmotor regions. However, its effects over
      the primary motor cortex have not been examined. Due to TMS device mechanical
      properties, 30Hz TBS is advantageous over 50Hz TBS in that it can be delivered at
      higher stimulation intensities. The goal of this pilot study is to examine the
      neurophysiologic effects of 30Hz TBS on the primary motor cortex (M1) of healthy
      adults. Eighteen right-handed adults (33+/-9.0 years; M:F=8:10) completed
      intermittent TBS (iTBS) or continuous TBS (cTBS) over left M1. TBS was performed
      with Magstim(r) SuperRapid2 with stimulation bursts (3 pulses at 30Hz) repeating
      every 200ms. For iTBS, each 2-s stimulation train was separated by 8s but there
      was no pause between trains for cTBS. Each TBS consisted of a total of 600 pulses
      delivered at an intensity of 90%*Resting Motor Threshold. Motor-Evoked Potentials
      (MEP) in the right first dorsal interosseous muscle were measured before, and one
      and ten minutes after TBS. Pre/post-TBS MEP amplitudes were compared using
      repeated-measures ANOVA. MEP amplitudes increased after 30Hz iTBS and decreased
      after 30Hz cTBS (TBS-Type*Time effect p=0.009). In conclusion, 30Hz TBS induced
      similar neurophysiologic effects over M1 as conventional 50Hz TBS.

PMID- 22627377
TI  - Cutaneous and electrically evoked glutamate signaling in the adult rat
      somatosensory system.
AB  - Glutamate neurotransmission plays critical roles in normal central nervous system
      (CNS) function, neurodegenerative diseases, and neurotrauma. We determined
      whether glutamate signaling could be evoked within the anesthetized normal adult
      rat CNS with clinically relevant peripheral stimulation and recorded (at >1Hz)
      with glutamate-sensitive, ceramic microelectrode arrays (MEAs). Basal glutamate
      levels and both forelimb cutaneous and electrical stimulation-evoked glutamate
      release were measured within the cuneate nucleus, a relay of the mammalian dorsal
      columns somatosensory system. The MEAs with triangular, sharp-point tips were
      more effective at tissue penetration than the flat, blunt tips. Basal glutamate
      levels of 2.1+/-4.4MUM (mean+/-SD, n=10 animals) were detected from 150MUm to
      1200MUm below the brainstem dorsal surface. Cutaneous evoked glutamate signals
      showed an amplitude of 1.1+/-1.1MUM and a duration of 7.3+/-6.5s (26 signals,
      n=6). Electrically evoked signals, like cutaneous ones, were both rapid and
      slowly rising. Electrically evoked signals, especially those evoked by
      stimulation trains, were more reproducible and had an amplitude of 1.2+/-1.4MUM,
      duration of 19.4+/-17.3s, and latency from stimulus onset of 21.3+/-21.5s (25
      signals, n=4). In contrast to cutaneous stimulation, glutamate signals evoked by
      electrical stimulation had longer durations and were recorded primarily in the
      middle and ventral cuneate nuclei. Importantly, both cutaneous and electrical
      stimulation of the contralateral forelimb and hindlimbs did not evoke glutamate
      signaling. With the use of MEAs, these results show, for the first time,
      somatosensory-pathway specific changes in glutamate levels during peripheral
      cutaneous and electrical stimulation.

PMID- 22627378
TI  - Improvement of collagenase distribution with the ductal preservation for human
      islet isolation.
AB  - A delivery of collagenase at the islet-exocrine interface is crucial for
      successful human islet isolation. In this study, we investigated how the ductal
      preservation method at the procurement site affected collagenase distribution. At
      first, we analyzed human islet isolation data among groups using Serva
      collagenase with or without ductal injection (DI) or using new Liberase MTF with
      DI. Then, to assess the distribution of collagenase, human pancreata were
      classified into two groups: without DI (no DI, n = 5) and with DI at the
      procurement site (DI, n = 5). Collagenase with 1% marking dye was perfused in the
      same manner as in our clinical isolation. The distension of the pancreas and the
      microscopic distribution of the dyed collagenase in pancreas sections were
      examined. For microscopic analysis, islets were counted and classified into three
      criteria: unreached, dye didn't reach the islet surface; surface, dye resided on
      the surface of the islet but not inside; and inside, dye was found inside the
      islet. As a result, DI groups substantially improved islet yields. In addition,
      Liberase MTF with DI significantly improved efficacy of pancreas digestion. All
      pancreata were well distended macroscopically. However, microscopically, the
      majority of islets in the no DI group were untouched by the dyed collagenase.
      Ductal preservation substantially improved dyed collagenase delivery on the
      surface of islets. In conclusion, delivery of collagenase on the surface of
      islets was unexpectedly insufficient without DI, which was substantially improved
      by DI. Thus, ductal preservation is a potent method to improve collagenase
      delivery and islet yields.

PMID- 22627379
TI  - Snap denaturation reveals dimerization by AraC-like protein Rns.
AB  - Here we show that the Rns regulator of Escherichia coli dimerises in vivo and in
      vitro. Furthermore, we demonstrate that Rns forms aggregates in vitro and
      describe a methodology to ameliorate aggregation thus permitting the analysis of
      Rns by cross-linking.

PMID- 22627380
TI  - Chromatin-modifying agents in anti-cancer therapy.
AB  - Epigenetic alterations are involved in every step of carcinogenesis. The
      development of chromatin-modifying agents (CMAs) has provided the ability to
      fight cancer by reversing these alterations. Currently, four CMAs have been
      approved for cancer treatment; two DNA demethylating agents and two deacetylase
      inhibitors. A number of promising CMAs are undergoing clinical trials in several
      cancer types. Moreover, already approved CMAs are still under clinical
      investigation to improve their efficacy and to extend their use to a broader
      panel of cancers. Combinatorial treatments with CMAs are already considered a
      promising strategy to improve clinical benefits and to limit side effects. The
      real mechanisms by which these CMAs allow the improvement and remission of
      patients are still obscure. A deeper analysis of the molecular features expressed
      by responding patients should be performed to reveal this information. In this
      review, we focus on clinical trials with CMAs, discussing the success and the
      pitfalls of this new class of anti-cancer drugs.

PMID- 22627381
TI  - Leptin and leptin receptor-related monogenic obesity.
AB  - The studies based on candidate genes and encoded proteins known to cause severe
      obesity in rodents, have shown that these genes also contribute to human early
      onset obesity especially for those involved in the leptin pathway: the leptin
      (LEP) and leptin receptor (LEPR) genes. Since 1997, less than 20 individuals
      carrying a LEP gene mutation have been identified. Patients are mostly
      characterized by severe early-onset obesity with severe hyperphagia and
      associated phenotype such hypogonadotrophic hypogonadism, high rate of infection
      associated with a deficiency in T cell and abnormalities of sympathetic nerve
      function. Therapeutic option (subcutaneous daily injection of leptin) is
      available for patients with LEP deficiency. It results in weight loss, mainly of
      fat mass, with a major effect on reducing food intake and on other dysfunctions
      including immunity and induction of puberty even in adults. In LEPR deficient
      subjects, phenotypic similarities with the LEP-deficient subjects were noticed,
      especially the exhibited rapid weight gain in the first few months of life, with
      severe hyperphagia and the endocrine abnormalities (hypogonadotrophic
      hypogonadism, insufficient somatotrophic or thyreotropic secretion). Leptin
      treatment is useless in the LEPR deficient subjects. Factors that could possibly
      bypass normal leptin delivery systems are being developed but are not yet
      currently available for the treatment of these patients. Measurement of
      circulating leptin may help for the diagnosis of such obesity: it is undetectable
      in LEP mutation carriers or extremely elevated in LEPR mutation carriers. Thus,
      LEPR gene screening might be also considered in subjects with the association of
      severe obesity with endocrine dysfunctions such as hypogonadism and with leptin
      related to corpulence level.

PMID- 22627382
TI  - Impaired drug-binding capacities of in vitro and in vivo glycated albumin.
AB  - Albumin, the major circulating protein in blood, can undergo increased glycation
      in diabetes. One of the main properties of this plasma protein is its strong
      affinity to bind many therapeutic drugs, including warfarin and ketoprofen. In
      this study, we investigated whether or not there were any significant changes
      related to in vitro or in vivo glycation in the structural properties and the
      binding of human albumin to both therapeutic drugs. Structural parameters,
      including redox state and ketoamine contents of in vitro and in vivo glycated
      purified albumins, were investigated in parallel with their affinity for warfarin
      and ketoprofen. High-performance liquid chromatography was used to determine the
      free drug concentrations and dissociation constants according to the Scatchard
      method. An alternative method based on fluorescence spectroscopy was also used to
      assess drug-binding properties. Oxidation and glycation levels were found to be
      enhanced in albumin purified from diabetic patients or glycated with glucose or
      methylglyoxal, after determination of their ketoamine, free thiol, amino group
      and carbonyl contents. In parallel, significant impairments in the binding
      affinity of in vitro and in vivo glycated albumin, as indicated by the higher
      dissociation constant values and confirmed by higher free drug fractions, were
      observed. To a lesser extent, this alteration also significantly affected
      diabetic albumin affinity, indicated by a lower static quenching in fluorescence
      spectroscopy. This work provides useful information supporting in vivo diabetic
      albumin could be the best model of glycation for monitoring diabetic
      physiopathology and should be valuable to know if glycation of albumin could
      contribute to variability in drugs response during diabetes.

PMID- 22627383
TI  - Identification of retinoblastoma related genes with shortest path in a protein
      protein interaction network.
AB  - This paper presents a new method for identifying retinoblastoma related genes by
      integrating gene expression profile and shortest path in a functional linkage
      graph. With the existing protein-protein interaction data from STRING, a weighted
      functional linkage graph is constructed. 119 consistently differentially
      expressed genes between retinoblastoma and normal retina were obtained from the
      overlap of two gene expression studies of retinoblastoma. Then the shortest paths
      between each pair of these 119 genes were determined with Dijkstra's algorithm.
      Finally, all the genes present on the shortest paths were extracted and ranked
      according to their betweenness and the 119 shortest genes with a betweenness
      greater than 100 and with a p-value less than 0.05 were selected for further
      analysis. We also identified 53 retinoblastoma related miRNAs from published
      miRNA array data and most of the 238 (119 consistently differentially expressed
      genes and 119 shortest path genes) retinoblastoma genes were shown to be target
      genes of these 53 miRNAs. Interestingly, the genes we identified from both the
      gene expression profiles and the functional protein association network included
      more cancer genes than did the genes identified from the gene expression profiles
      alone. In addition, these genes also had greater functional similarity to the
      reported cancer genes than did the genes identified from the gene expression
      profiles alone. This study shows promising results and proves the efficiency of
      the proposed methods.

PMID- 22627384
TI  - Molecular characterization of a thermostable L-fucose isomerase from Dictyoglomus
      turgidum that isomerizes L-fucose and D-arabinose.
AB  - A recombinant thermostable l-fucose isomerase from Dictyoglomus turgidum was
      purified with a specific activity of 93 U/mg by heat treatment and His-trap
      affinity chromatography. The native enzyme existed as a 410 kDa hexamer. The
      maximum activity for l-fucose isomerization was observed at pH 7.0 and 80 
      degrees C with a half-life of 5 h in the presence of 1 mM Mn(2+) that was present
      one molecular per monomer. The isomerization activity of the enzyme with aldose
      substrates was highest for l-fucose (with a k(cat) of 15,500 min(-1) and a K(m)
      of 72 mM), followed by d-arabinose, d-altrose, and l-galactose. The 15 putative
      active-site residues within 5 A of the substrate l-fucose in the homology model
      were individually replaced with other amino acids. The analysis of metal-binding
      capacities of these alanine-substituted variants revealed that Glu349, Asp373,
      and His539 were metal-binding residues, and His539 was the most influential
      residue for metal binding. The activities of all variants at 349 and 373
      positions except for a dramatically decreased k(cat) of D373A were completely
      abolished, suggesting that Glu349 and Asp373 were catalytic residues. Alanine
      substitutions at Val131, Met197, Ile199, Gln314, Ser405, Tyr451, and Asn538
      resulted in substantial increases in K(m), suggesting that these amino acids are
      substrate-binding residues. Alanine substitutions at Arg30, Trp102, Asn404,
      Phe452, and Trp510 resulted in decreases in k(cat), but had little effect on
      K(m).

PMID- 22627385
TI  - A new ADAMTS13 missense mutation (D1362V) in thrombotic thrombocytopenic purpura
      diagnosed during pregnancy.

PMID- 22627390
TI  - Selectin-mediated adhesion in shear flow using micropatterned substrates:
      multiple-bond interactions govern the critical length for cell binding.
AB  - Receptor-ligand adhesive interactions play a pivotal role in diverse biological
      processes including inflammation and cancer metastasis. Cell adhesion is mediated
      by the molecular recognition of membrane-bound receptors by their cognate ligands
      on apposing cells. Cell-cell binding is regulated by distinct parameters such as
      the receptor-ligand binding kinetics, the tensile strength of individual bonds,
      the involvement of multiple bonds and their modulation by hydrodynamic shear.
      This work aims to investigate the interplay of these parameters on selectin
      mediated cell adhesion in shear flow. We designed a microfluidic device that
      delivers cells in a single file over a receptor-functionalized substrate, thereby
      permitting accurate determination of the cell flux. The selectin(s) was presented
      on striped patches of fixed width and varying length. We identified the critical
      patch lengths of P- and L-selectin for the initiation of HL-60 cell binding in
      shear flow. This characteristic length is governed by the time required to form
      multiple-bond interactions, as revealed by a multiple-bond mathematical model.
      The number of bonds required to support cell binding increases with the applied
      shear stress (0.5-2 dyn cm(-2)) for L- but not P-selectin. This finding is
      explained by differences in the tensile strength of P- and L-selectin for PSGL-1.
      Our integrated experimental and mathematical approach advances our understanding
      of receptor-mediated cell adhesion in the vasculature. Detailed knowledge of how
      molecular interactions modulate macroscopic cell binding behavior pertinent to
      inflammation and metastasis would facilitate the development of promising
      diagnostic tools to combat these diseases.

PMID- 22627391
TI  - A case of bronchial asthma complicated by epidural emphysema.

PMID- 22627393
TI  - Facile synthesis of functional Au nanopatches and nanocups.
AB  - This communication describes a one-step strategy for the facile synthesis of
      polymer-Au patchy particles (PPs) and Au nanocups using the interfacial
      reactions.

PMID- 22627392
TI  - In vivo selection of autologous MGMT gene-modified cells following reduced
      intensity conditioning with BCNU and temozolomide in the dog model.
AB  - Chemotherapy with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide
      (TMZ) is commonly used for the treatment of glioblastoma multiforme (GBM) and
      other cancers. In preparation for a clinical gene therapy study in patients with
      glioblastoma, we wished to study whether these reagents could be used as a
      reduced-intensity conditioning regimen for autologous transplantation of gene
      modified cells. We used an MGMT(P140K)-expressing lentivirus vector to modify dog
      CD34(+) cells and tested in four dogs whether these autologous cells engraft and
      provide chemoprotection after transplantation. Treatment with O(6)-benzylguanine
      (O6BG)/TMZ after transplantation resulted in gene marking levels up to 75%,
      without significant hematopoietic cytopenia, which is consistent with
      hematopoietic chemoprotection. Retrovirus integration analysis showed that
      multiple clones contribute to hematopoiesis. These studies demonstrate the
      ability to achieve stable engraftment of MGMT(P140K)-modified autologous
      hematopoietic stem cells (HSCs) after a novel reduced-intensity conditioning
      protocol using a combination of BCNU and TMZ. Furthermore, we show that
      MGMT(P140K)-HSC engraftment provides chemoprotection during TMZ dose escalation.
      Clinically, chemoconditioning with BCNU and TMZ should facilitate engraftment of
      MGMT(P140K)-modified cells while providing antitumor activity for patients with
      poor prognosis glioblastoma or alkylating agent-sensitive tumors, thereby
      supporting dose-intensified chemotherapy regimens.

PMID- 22627394
TI  - High-frequency variant p.T60M in NaCl cotransporter and blood pressure
      variability in Han Chinese.
AB  - OBJECTIVE: Frequent studies have confirmed that homozygous or compound
      heterozygous loss-of-function mutation p.Thr60Met in NaCl cotransporter (NCC)
      lead to the salt-wasting Gitelman's syndrome (GS) of hypotension. The finding
      that Thr60 is a key SPAK/OSR1 phosphorylation site on NCC also raises the
      possible importance of Thr60 in regulating the activity of NCC and blood pressure
      (BP). However, the association of heterozygous NCC mutation p.Thr60Met and BP has
      not yet been studied. METHODS: We collected 38 heterozygous mutation p.Thr60Met
      carriers, respectively, from 14 GS families confirmed by our previous studies and
      1,000 unrelated Han Chinese, and matched them pairwise (sex, age +/-2 years and
      BMI +/-1) with 38 unrelated healthy controls. BP and biochemistry data were
      obtained. Student's t test and chi(2) test were used to compare the differences
      between these study subjects with the heterozygous variant p.T60M and the
      controls. p < 0.05 was considered statistically significant. RESULTS: p.Thr60Met
      carriers had markedly lower BP (systolic 110.3 +/- 13.5 vs. 119.1 +/- 15.0 mm Hg;
      diastolic 70.2 +/- 7.0 vs. 75.4 +/- 8.2 mm Hg, p < 0.01) than controls.
      p.Thr60Met heterozygotes had higher fasting plasma glucose concentration (5.35 +/
      0.73 vs. 4.95 +/- 0.69 mmol/l, p < 0.01). 14 carriers versus 6 control subjects
      had impaired fasting glucose (36.8 vs. 15.8%, p < 0.01), and p.Thr60Met carriers
      had higher 24-hour urinary sodium excretion than controls but not significantly
      (170.2 +/- 35.6 vs. 159.5 +/- 39.0 mmol, p = 0.10). CONCLUSIONS: The NCC mutation
      p.Thr60Met carriers in Han populations have markedly lower BP and slightly higher
      fasting plasma glucose compared with normal controls.

PMID- 22627395
TI  - A new ratiometric and colorimetric chemosensor for cyanide anion based on
      coumarin-hemicyanine hybrid.
AB  - A hybrid coumarin-hemicyanine dye, Cou-BT, was developed as a new ratiometric and
      colorimetric sensor for cyanide with a sensing mechanism via nucleophilic
      addition of cyanide anion to the benzothiolium group. Cou-BT shows high
      sensitivity and selectivity for cyanide detection over other common anion species
      in aqueous acetonitrile solution. The calculated pseudo-first-order rate constant
      for cyanide anion addition was (2.13 +/- 0.08) * 10(-2) s(-1) at 298 K, and the
      detection limit was estimated to be 0.64 MUM. The DFT and TDDFT calculation
      results suggest that the ratiometric and colorimetric sensing behavior of Cou-BT
      upon its reaction with cyanide was due to the interrupted pi-conjugation and
      blocked ICT progress.

PMID- 22627397
TI  - Stem cells in plastic surgery--new applications in evolution.

PMID- 22627396
TI  - The most negatively charged low-density lipoprotein L5 induces stress pathways in
      vascular endothelial cells.
AB  - BACKGROUND/AIMS: L5, the most negatively charged species of low-density
      lipoprotein (LDL), has been implicated in atherogenesis by inducing apoptosis of
      endothelial cells (ECs) and inhibiting the differentiation of endothelial
      progenitor cells. In this study, we compared the effects of LDL charge on
      cellular stress pathways leading to atherogenesis. METHODS: We isolated L5 and L1
      (the least negatively charged LDL) from the plasma of patients with familial
      hypercholesterolemia and used JC-1 staining to examine the effects of L5 and L1
      on the mitochondrial membrane potential (DCm) in human umbilical vein ECs
      (HUVECs). Additionally, we characterized the gene expression profiles of 7
      proteins involved in various types of cellular stress. RESULTS: The DCm was
      severely compromised in HUVECs treated with L5. Furthermore, compared with L1, L5
      induced a decrease in mRNA and protein expression of the endoplasmic reticulum
      (ER) chaperone proteins ORP150, Grp94, and Grp58, mitochondrial proteins Prdx3
      and ATP synthase, and an increase in the expression of the pro-inflammatory
      protein hnRNP C1/C2. CONCLUSIONS: Our work suggests that L5, but not L1, may
      promote the destruction of ECs that occurs during atherogenesis by causing
      mitochondrial dysfunction and modulating the expression of key proteins to
      promote inflammation, ER dysfunction, oxidative stress, and apoptosis.

PMID- 22627399
TI  - Highlights of the proceedings from the 14th International Congress of the
      International Society of Craniofacial Surgery: ISCFS 2011, Livingston, Zambia.

PMID- 22627398
TI  - Craniofacial reconstruction with induced pluripotent stem cells.

PMID- 22627401
TI  - Commentary on "New Resorbable Plate and Screw System in Pediatric Craniofacial
      Surgery".

PMID- 22627402
TI  - Sectional anatomy aid for improvement of decompression surgery approach to
      vertical segment of facial nerve.
AB  - The aim of this study was to find a surgical approach to a vertical segment of
      the facial nerve (VFN) with a relatively wide visual field and small lesion by
      studying the location and structure of VFN with cross-sectional anatomy. High
      resolution spiral computed tomographic multiplane reformation was used to reform
      images that were parallel to the Frankfort horizontal plane. To locate the VFN,
      we measured the distances as follows: from the VFN to the paries posterior bony
      external acoustic meatus on 5 typical multiplane reformation images, to the
      promontorium tympani and the root of the tympanic ring on 2 typical images. The
      mean distances from the VFN to the paries posterior bony external acoustic meatus
      are as follows: 4.47 mm on images showing the top of the external acoustic
      meatus, 4.20 mm on images with the best view of the window niche, 3.35 mm on
      images that show the widest external acoustic meatus, 4.22 mm on images with the
      inferior margin of the sulcus tympanicus, and 5.49 mm on images that show the
      bottom of the external acoustic meatus. The VFN is approximately 4.20 mm lateral
      to the promontorium tympani on images with the best view of the window niche and
      4.12 mm lateral to the root of the tympanic ring on images with the inferior
      margin of the sulcus tympanicus. The other results indicate that the area and
      depth of the surgical wound from the improved approach would be much smaller than
      that from the typical approach. The surgical approach to the horizontal segment
      of the facial nerve through the external acoustic meatus and the tympanic cavity
      could be improved by grinding off the external acoustic meatus to show the VFN.
      The VFN can be found by taking the promontorium tympani and tympanic ring as
      references. This improvement is of high potential to expand the visual field to
      the facial nerve, remarkably without significant injury to the patients compared
      with the typical approach through the mastoid process.

PMID- 22627403
TI  - Internal carotid artery in the operative plane of endoscopic endonasal
      transsphenoidal surgery.
AB  - The objective of this study was to measure the related parameters of intercarotid
      artery (ICA) in the operative plane of endonasal transsphenoidal approach for
      hypophyseal surgeries. Nine parameters of the ICA were examined in the computed
      tomographic angiographic (CTA) scan of 101 patients. The shortest distance
      between the middle point of the nasal columella and the projective point of the
      ICA (D(3)) was 85.50 (5.79) mm. The shortest distance between the anterior wall
      of the sphenoid sinus and the projective point of the ICA (D(4)) was 16.93 (3.50)
      mm. The distance between the bilateral projective points of the ICA (D(5)) was
      21.60 (3.45) mm. The shortest distance from the anterior wall of the sphenoid
      sinus to the line between the bilateral projective points of the ICA (D(6)) was
      12.1 (3.91) mm. The shortest distance between the middle point of nasal columella
      and the anterior wall of the sphenoid sinus (D(7)) was 72.67 (5.99) mm. The width
      of the angle between the bilateral ICA projective point from the middle point of
      the nasal columella (A(1)) was 14.9 (2.32) degrees. The width of the angle
      between the bilateral ICA projective points from the anterior-most point of
      sphenoid sinus (A(2)) was 85.49 (18.12) degrees. Clinically, it is relatively
      safe to work within the distances and angles measured in this research, and these
      results may provide information for clinical surgery of pituitary tumor.

PMID- 22627404
TI  - Effect of endothelial differentiated adipose-derived stem cells on vascularity
      and osteogenesis in poly(D,L-lactide) scaffolds in vivo.
AB  - Prevascularization of engineered bony constructs can potentially improve in vivo
      viability. However, the effect of endothelial cells on osteogenesis is unknown
      when placed in poly(D,L-lactide) (PLA) scaffolds alone. Adipose-derived stem
      cells (ASCs) have the ability to differentiate into both osteoblasts and
      endothelial cells by culture in specific media. We hypothesized that ASC-derived
      endothelial cells would improve vascularity with minimal contribution to bone
      formation when placed in scaffold alone. ASCs were successfully differentiated
      into endothelial cells (ASC-Endo) and osteoblasts (ASC-Osteo) using media
      supplemented with vascular endothelial growth factor and bone morphogenic protein
      2, respectively. Tissue-engineered constructs were created with PLA matrices
      containing no cells (control), undifferentiated ASCs (ASCs), osteogenic
      differentiated ASCs (ASC-Osteo), or endothelial differentiated ASCs (ASC-Endo),
      and these constructs were evaluated in critical-size Lewis rat calvarial defect
      model (n = 34). Eight weeks after implantation, the bone volume and microvessel
      population of bony constructs were evaluated by micro-computed tomography
      analysis and histologic staining. Bone volumes for ASCs and ASC-Osteo constructs,
      0.7 and 0.91 mm(3), respectively, were statistically greater than that for ASC
      Endo, 0.28 mm(3) (P < 0.05). There was no statistical difference between the PLA
      control (0.5 mm(3)) and ASC-Endo (0.28 mm(3)) constructs in bone formation. The
      percent area of microvessels within constructs was highest in the ASC-Endo group,
      although it did not reach statistical significance (0.065). Prevascularization of
      PLA scaffold with ASC-Endo cells will not increase bone formation by itself but
      may be used as a cell source for improving vascularization and potentially
      improving existing osteoblast function.

PMID- 22627405
TI  - Tissue interactions between craniosynostotic dura mater and bone.
AB  - BACKGROUND: Cells within the dura mater have been implicated in the determination
      of suture patency and fusion. Craniosynostosis (CS), the premature fusion of 1 or
      more of the cranial sutures, could result from abnormal control over the
      differentiation of osteoprogenitor cells from the dura mater. This study tested
      whether dura mater cells derived from rabbits with congenital CS were different
      from cells derived from normal rabbits and investigated the effects that CS dura
      mater had on osteogenic differentiation in vitro and in vivo. METHODS: Cells were
      derived from the dura mater from wild-type rabbits (WT; n = 23) or CS rabbits (n
      = 16). Cells were stimulated with bone morphogenetic protein 4, and alkaline
      phosphatase (ALP) expression and cell proliferation were assessed. Dura mater
      derived cells were also cocultured with primary rabbit bone-derived cells, and
      ALP was assessed. Finally, interactions between the dura mater and overlying
      tissues were manipulated in vivo. RESULTS: Craniosynostotic dura mater-derived
      cells proliferated faster than did WT cells but were not more ALP positive.
      Coculture experiments showed that CS dura mater cells induced increased ALP
      activity in CS bone-derived cells, but not in WT bone-derived cells. In vivo
      experiments showed that a physical barrier successfully inhibited dura mater
      derived osteogenesis. CONCLUSIONS: Coculture of CS bone- and CS dura mater
      derived cells evoked an abnormal phenotype in vitro. Covering the CS dura mater
      led to decreased bone formation in vivo. Further investigations will focus on the
      signaling molecules involved in the communication between these 2 CS tissue types
      in vitro and in vivo.

PMID- 22627406
TI  - Preliminarily measurement and analysis of sawing forces in fresh cadaver mandible
      using reciprocating saw for reality-based haptic feedback.
AB  - PURPOSE: The aim of the study was to preliminarily measure and analyze the
      cutting forces in fresh Chinese cadaver mandible using a clinically widely used
      reciprocating saw for reality-based haptic feedback. METHODS: Eight mandibles
      were taken from fresh Chinese cadavers, 4 females and 4 males, aged between 59
      and 95 years. A set of sawing experiments, using a surgery Stryker micro
      reciprocating saw and Kistler piezoelectric dynamometer, was carried out by a CNC
      machining center. Under different vibration frequencies of saw and feeding rates
      measured from orthognathic surgery, sawing forces were recorded by a signal
      acquisition system. RESULTS: Remarkably different sawing forces were measured
      from different cadavers. Feed and vibration frequency of the reciprocating saw
      could determine the cutting forces only on 1 body. To reduce the impact of bone
      thickness changes on the cutting force measurements, all the cutting force data
      should be converted to the force of unit cutting length. The vibration frequency
      of haptic feedback system is determined by main cutting forces. Fast Fourier
      transform method can be used to calculate the frequency of this system. To
      simulate surgery in higher fidelity, all the sawing forces from the experiment
      should be amended by experienced surgeons before use in virtual reality surgery
      simulator. CONCLUSIONS: Sawing force signals of different ages for force feedback
      were measured successfully, and more factors related to the bone mechanical
      properties, such as bone density, should be concerned in the future.

PMID- 22627407
TI  - Herpes zoster developing within recent subciliary incision scar.
AB  - Herpes zoster is a common dermatologic disease characterized by unilateral pain
      and vesicular lesions over the unilateral sensory dermatomes being caused by the
      reactivation of varicella zoster virus, and its incidence seems to be increasing
      recently. In case of involving the ganglion of the fifth cranial nerve
      (trigeminal nerve), it can descend down the affected nerve into the skin, then
      producing an eruption in the dermatome. Among the patients with this disease,
      about 40% to 50% had associated conditions such as diabetes mellitus,
      hypertension, pulmonary tuberculosis, liver diseases, peptic ulcer,
      hypothyroidism, or pharyngitis but rarely facial trauma. Generally, herpes zoster
      was commonly associated with systemic disorders, and the treatment duration was
      prolonged in associated diseases. However, herpes zoster occurring specifically
      at the site of previously traumatized facial bone has not yet been reported.
      Retrospective study of 1 case of herpes zoster with blow-out fracture, which had
      been treated with acyclovir and steroid, was done. Follow-up length was about 3
      months. After treatment, the patient became stable, and there was no
      complication. We treated herpes zoster developing within a recent operative
      subciliary scar, and the case is presented with the review of literature.
      Finally, facial trauma or reconstruction of the orbital floor with alloplastic
      implant might be a risk factor for herpes zoster in traumatized patient.

PMID- 22627408
TI  - Contouring of the forehead irregularities (washboard effect) with bone
      biomaterial.
AB  - Calvarial vault defects may be repaired with autologous bone or alloplastic
      materials, such as methyl methacrylate, hydroxyapatite, titanium, or porous
      polyethylene. The criterion standard for repairing small cranial defects is
      autogenous bone from iliac crest or split calvarial grafts. However, autogenous
      grafts may result in donor-site morbidity, increased operative time,
      reabsorption, blood loss, and additional time for recovery. An alloplastic
      material should have some ideal properties, including easy adaptation,
      biocompatibility, which permit ingrowth of new tissue, stability of shape, and
      low rate of reabsorption. An implant in this area should be easily shaped and
      positioned, allowing an easy tissue in growth.The authors report the case of a 50
      year-old man with a deformity of the frontal region as a result of a frontonaso
      orbitoethmoidal fracture after reduction and fixation of the fractures and right
      frontal sinus cranialization with frontal craniotomy via coronal approach. The
      deformity caused the typical aspect (washboard effect). Correction and
      reconstruction were performed by using Cerament (Bonesupport AB, Lund, Sweden),
      alloplastic biphasic material, composed of 60% alpha-hemihydrate of calcium
      sulfate and 40% hydroxyapatite. Four years after the surgery, the patient had
      recovered with satisfactory morphology of the forehead as well as disappearance
      of the frowning look in the frontal region.

PMID- 22627409
TI  - Versatile use of submental tissue for reconstruction of perioral soft tissue
      defects.
AB  - To obtain optimum aesthetic result, perioral soft tissue defects require
      reconstruction using similar tissue. The submental area has very similar
      characteristics to perioral soft tissue and consists of thin, pliable tissue with
      a perfect color match. Therefore, we have used submental tissues for
      reconstruction of perioral soft tissue defects and application of the techniques,
      and results are discussed in this article. Between February 2001 and April 2008,
      14 perioral soft tissue reconstruction procedures using the submental tissues
      were performed. The defect was on the upper lip including nasal columella in 5
      cases, mentum in 3 cases, and oral commissure including buccal cheek in 6 cases.
      The techniques that were used included composite graft in 3 cases, local
      advancement flap in 3 cases, pedicled flap in 5 cases, and free flap in 3 cases.
      Patients were followed up for 9 months to 5 years. During this period, no major
      complications were noted, and satisfactory aesthetic results were obtained. All
      transferred submental tissues survived. In all patients, donor defects were
      closed primarily except in cases of local advancement flap. The donor-site scar
      was inconspicuous and well hidden below the mandibular margin and did not
      restrict neck motion in all patients. In particular, hair restoration on the flap
      was excellent in male patients. We believe that the submental area can provide
      useful soft tissue for perioral soft tissue defects because it provides a good
      color and texture match with perioral skin and can be harvested with minimal
      donor-site morbidity.

PMID- 22627410
TI  - Measurements for the direct approach to the oval foramen to apply mandibular
      nerve blockade.
AB  - PURPOSE: The lack of certain quotable landmarks and not taking the morphometric
      variations into consideration for mandibular nerve blockade can cause some
      complications. The aim of this study was to ensure there are data for more
      feasible and successful lateral extraoral approach to block the mandibular nerve
      by proposing reliable and quotable landmarks. METHODS: The current study was
      carried out on 55 skulls at the anatomy departments of the Universities of Mersin
      and Ankara. The length of the zygomatic arch, measurements indicating the
      puncture point (PP), injection depth, and injection angle were revealed. The
      differences between sides and the relationships between the parameters were
      evaluated by using paired t-test and Pearson correlation test, respectively.
      RESULTS: Of all skulls, it is observed that the injection line passed anterior to
      the articular surface of the temporomandibular joint. The distance between
      external acoustic opening and PP showed positive correlation with the distance
      between oval foramen and the midpoint of the zygomatic arch on the left side (r =
      0.364, P = 0.001). On the right, the correlation was close to the statistically
      significant level (r = 0.280, P = 0.072). The distance between external acoustic
      opening and PP that can be adapted to the living subjects was found as 26.31 +/-
      1.95 mm. Injection angle to the coronal plane was measured to be 16.39 +/- 2.96
      degrees. The difference between sides for this parameter was not statistically
      significant. CONCLUSIONS: The determined parameters are suggested to be
      convenient and quotable to help in successful direct application under three
      dimensional computed tomography or computed tomography-fluoroscopy for blocking
      the mandibular nerve.

PMID- 22627416
TI  - Torn earlobe caused by an earring trapped in the net of goalposts.

PMID- 22627417
TI  - Selection of osteotomy type in selected group of patients for rhinoplasty.

PMID- 22627418
TI  - Posttraumatic severe epistaxis and its safe management.

PMID- 22627419
TI  - Pharyngeal suturing made easier and safer by the Peruvian fisherman's knot.

PMID- 22627420
TI  - Osseous regeneration of the free fibula flap resembling a firm mass after
      mandible reconstruction.

PMID- 22627421
TI  - Giant neglected desmoplastic ameloblastoma:  reconstruction with free fibula
      flap.
AB  - The desmoplastic ameloblastoma (DA) is a rare variant of the conventional
      ameloblastoma. It accounts for only 4% to 13% of all ameloblastomas. In this
      article, we describe the case of a young child affected by a giant neglected DA
      of the jaw. Preoperative biopsy demonstrated the extremely rare osteoplastic
      variant of DA. The patient was submitted to segmental mandibulectomy and
      immediate reconstruction with a free fibula osseous flap. The postoperative
      period was uneventful. The patient was very satisfied with the functional and
      aesthetic results of the procedure. In case of such rare variants of
      ameloblastoma, it is mandatory to preoperatively recognize them to allow the
      adequate treatment modality to be provided.

PMID- 22627422
TI  - Functional aesthetic treatment of patient with phenytoin-induced gingival
      overgrowth.
AB  - Gingival overgrowth (GO) may be related to the frequent use of certain
      medications, such as cyclosporin, phenytoin (PHT), and nifedipine, and is
      therefore denominated drug-induced GO. This article reports a case of a patient
      who with chronic periodontitis made use of PHT and presented generalized GO. A 30
      year-old man with GO was referred to the clinic of the Universidade Estadual
      Paulista, Brazil. The complaint was poor aesthetics because of the GO. The
      patient had a medical history of a controlled epileptic state, and PHT was
      administered as an anticonvulsant medication. The clinical examination showed
      generalized edematous gingival tissues and presence of bacterial plaque and
      calculus on the surfaces of the teeth. The diagnosis was GO associated with PHT
      because no other risk factors were identified. Treatment consisted of meticulous
      oral hygiene instruction, scaling, root surface instrumentation, prophylaxis, and
      daily chlorhexidine mouth rinses. After this stage, periodontal surgery was
      performed, and histopathologic evaluation was made. The patient has been under
      control for 3 years after the periodontal surgery, and up to the present time,
      there has been no recurrence. It can be concluded that PHT associated with the
      presence of irritants favored gingival growth and that the association of
      nonsurgical and surgical periodontal therapies was effective in the treatment of
      GO. Besides, motivating the patient to maintain oral hygiene is a prerequisite
      for the maintenance of periodontal health.

PMID- 22627423
TI  - Maxillary fungus ball caused by retained foreign bodies for 25 years.
AB  - We present a case of a maxillary fungus ball caused by retained foreign bodies
      for 25 years. The patient sustained a stab wound in the left face 25 years ago.
      The patient had no symptoms and complications of a foreign body, until the
      patient went to the hospital. The fungus ball and foreign bodies were removed via
      an endoscopic and Caldwell-Luc approach. We suggest the need for careful
      inspection and radiologic studies to localize occult foreign bodies in the
      sinonasal cavity or facial soft tissues after facial trauma.

PMID- 22627424
TI  - Low-grade central osteosarcoma of the orbit.
AB  - Low-grade central osteosarcoma is a rare type of osteosarcoma, representing fewer
      than 2% of all osteosarcomas. Approximately 80% of these tumors are located in
      the long bones, and they are particularly common in the distal and proximal
      tibia. However, they are rare in the craniofacial bones, and this tumor type has
      never been reported to occur in the orbit. In this report, a case of low-grade
      central osteosarcoma arising from the orbit is presented. The differential
      diagnoses of this tumor and the surgical results of radical resection and
      reconstruction are also presented.

PMID- 22627425
TI  - Scar due to skin incision for screw fixation through the transbuccal approach
      after sagittal split ramus osteotomy.
AB  - Most rigid fixation techniques after sagittal split ramus osteotomies of the
      mandible involve the transbuccal approach. A skin incision in the cheek carries
      with it possible undesirable sequelae, such as noticeable scarring. The aim of
      this study was to investigate whether there is scarring in the face after this
      technique. For screw insertion, a 5-mm stab incision was performed on 40 Japanese
      patients (20 men and 20 women) with class III occlusion. After surgery, gross
      examination (via the naked eyes) of the skin incision was performed monthly for 1
      year by the same oral surgeon. In all cases, the skin incision had disappeared by
      1 year after the surgery.

PMID- 22627426
TI  - Reconstructive procedure of lower lip defect due to ecthyma gangrenosum--a rare
      complication of acute lymphoblastic leukemia.
AB  - Ecthyma gangrenosum is a rare invasive cutaneous infection mostly caused by
      Pseudomonas aeruginosa in immunosuppressed patients, especially during
      neutropenic states. Embolic lesions usually accompanying with septicemia of P.
      aeruginosa are typically painless, round, and centrally necrotic with a
      surrounding erythematous halo. Facial involvement occurred only in 6% of the
      patients, which may result to complicated defects for reconstruction. In this
      article, we aimed to present a case with relapse of acute lymphoblastic leukemia
      presented to our clinic with 50% defect of the lower lip due to ecthyma
      gangrenosum and its late-term reconstruction.

PMID- 22627427
TI  - Conservative management of a large keratocystic odontogenic tumor in the maxilla.
AB  - Keratocystic odontogenic tumor is characterized by high recurrence rates.
      Conservative or aggressive management has been suggested as a method of
      treatment. Decompression is a conservative treatment that has been used in the
      treatment of large odontogenic cysts. The authors report a case of a 14-year-old
      patient with a keratocystic odontogenic tumor located in the right maxilla, which
      was treated by decompression followed by enucleation with curettage. The lesion
      did not recur on follow-up for 3 years after the enucleation surgery.

PMID- 22627428
TI  - New collagen matrix to avoid the reduction of keratinized tissue during guided
      bone regeneration in postextraction sites.
AB  - For decades, there has been an ongoing controversy regarding the need for an
      "adequate" width of keratinized gingiva/mucosa to preserve periodontal and
      implant health. Today, the presence of a certain width of keratinized tissue is
      recommended for achieving long-term periodontal and implant success, and
      therefore, a new collagen matrix has been developed to enhance the width of
      keratinized gingiva/mucosa. During postextraction socket preservation, guided
      bone regeneration techniques require complete coverage of the barrier membrane to
      reduce the risk of infection, occasionally causing a reduction of the width of
      keratinized tissue. Using the new collagen matrix, it is possible to leave the
      membrane intentionally uncovered, without suturing the surgical flap above it, to
      avoid the reduction of such tissue.

PMID- 22627429
TI  - Rectangular body ostectomy for the treatment of severe mandibular prognathism.
AB  - OBJECTIVE: The aim of this article was to present the surgical technique and the
      outcomes of rectangular body ostectomy in the treatment of severe mandibular
      prognathism. METHODS: Mandibular setback by bilateral rectangular body
      ostectomies combined with Le Fort I level maxillary advancement was performed.
      The deep bony concavity of paranasal area was grafted with bone blocks harvested
      from the ostectomized segments of the mandible. RESULTS: Satisfactory functional
      and aesthetic outcomes were obtained by rectangular body ostectomy combined with
      Le Fort I level maxillary advancement and an acceptable profile was provided for
      the patient. CONCLUSIONS: The mandibular rectangular ostectomy remains a safe and
      versatile procedure with predictable results in well-selected cases.

PMID- 22627430
TI  - Is the coexistence of intraoral synechia and cleft palate anomaly a sequence?
AB  - Intraoral synechia is a rarely seen intraoral anomaly. As a result of intraoral
      synechiae, fusion of the palatal shelves may be prevented because of the abnormal
      interposition of the tongue. Hence, cleft palate anomaly accompanies intraoral
      synechiae in many patients. The main problem for these patients is the inadequate
      oral opening for feeding. Flexible nasopharyngeal examination before intubation
      may help the anesthetist for simple excision of synechiae in the newborn period.
      In this article, a newborn who had a congenital synechia between the mandible and
      the maxilla has been presented, and the etiopathogenesis of intraoral synechia
      and the importance of flexible nasal endoscopy before endotracheal intubation are
      discussed.

PMID- 22627431
TI  - Analysis of complications following endoscopically assisted treatment of
      mandibular condylar fractures.
AB  - BACKGROUND: Within the field of facial reconstructive surgery, minimally invasive
      procedures are used for the treatment of temporomandibular joint disorders,
      traumas, and salivary glands and base of skull tumors. The recent report of
      endoscopic approach for treating subcondylar fractures of the mandible is
      designed to provide a new method for the treatment of subcondylar fractures using
      an endoscope through a limited transoral incision. To the best of our knowledge,
      the advantages and the disadvantages of an endoscopically assisted approach to
      mandibular condylar fracture have not been verified in studies with a high level
      of evidence. The objective of this article was to present our experience
      regarding the endoscopically assisted reduction of subcondylar mandibular
      fractures with a special focus on complications. METHODS: The records of 14
      patients who underwent surgical repair of subcondylar fractures by transoral
      endoscopic-assisted technique from January 2005 to December 2008 at the
      Maxillofacial Surgery Unit of Novara Major Hospital were reviewed
      retrospectively. The measures for the surgical objectives included the following
      outcome variables: (1) operation time, (2) cosmetic outcome, (3) salivary
      fistulas, (4) infection, (5) delayed wound healing, (6) facial nerve damage, (7)
      hemorrhage, (8) repeat interventions, (9) bone consolidation, (10) occlusion
      changes, and (11) temporomandibular joint dysfunction. RESULTS: Our data show
      that we have had 4 complications (28%) experienced by 4 different patients: (1)
      arterial hemorrhage, (2) facial nerve injury, (3) nonunion, and (4) partial
      condylar reabsorption. CONCLUSIONS: Although we cannot draw statistically
      significant conclusions, we think that further randomized clinical trials should
      be necessary to analyze this method; we believe that there is not an ideal
      approach for a fracture, but each patient needs to be fully evaluated carefully
      preoperatively, and the more convenient approach needs to be selected for each
      case.

PMID- 22627432
TI  - Three-dimensional analysis of maxillary anatomic landmarks for greater palatine
      nerve block anesthesia.
AB  - Greater palatine nerve block anesthesia (GPNBA) is a local anesthetic procedure
      used for maxillary and nasal treatment. Investigation of the three-dimensional
      anatomic location of the greater palatine foramen (GPF) is important for
      successful local anesthesia. The study aim was to provide standards for anatomic
      structures in the oral cavity that can be easily referred to in GPNBA. Maxillary
      computed tomography data were obtained from patients between 8 and 16 years of
      age whose maxillary incisors and first molars had already erupted (the growth
      group, n = 103); changes in the maxilla were observed over time in this group.
      Reference values for GPNBA in adults were measured in 107 patients older than 18
      years. Maxillary computed tomography images were reconstructed three
      dimensionally. Regression analysis demonstrates that all maxillary measurements
      in the growth group except for the distance from the posterior nasal spine to the
      GPF in the coronal plane correlated significantly with age. In adults, the mean
      perpendicular distance from the interdental alveolar bone between the left and
      right central incisors (1alvB) to the GPF in the coronal plane was 46.16 mm, and
      the mean distance from 1alvB to the GPF was 51.05 mm. The mean distance from the
      maxillary central incisor to the GPF was 57.58 mm. The mean angle between the
      line from the maxillary central incisor to each GPF and the sagittal plane was
      16.49 degrees. The mean perpendicular distance from the anterior nasal spine to
      the GPF in the coronal plane was 43.49 mm, whereas the mean perpendicular
      distance from the GPF to the bone plane was 12.67 mm, and the mean perpendicular
      distance from the GPF to the occlusal plane was 22.13 mm. These measurements can
      be used to find the height of the GPF. In adults, the measured perpendicular
      distance from the incisive foramen to the GPF in the coronal plane was 32.04 mm,
      and the perpendicular distance from the median of the line that connects both of
      the contact points between the maxillary tuberosity and the pterygoid plate to
      the GPF in the coronal plane was 5.23 mm. Three-dimensional reference values
      relative to the anatomic structures in the oral cavity may increase the success
      rate of GPNBA and reduce complications. Although the maxillary growth pattern was
      analyzed, a limitation of this study is that maxillary anatomic measurements were
      not analyzed with regard to race or ethnicity.

PMID- 22627434
TI  - Parotid gland tumors in a Korean population.
AB  - Salivary gland tumors occur in about 3% of the head and neck tumors, and among
      the salivary gland tumors, parotid gland tumor occurs in about 80%. Because of
      its low frequency and small cases, it is hard to establish the epidemiologic
      characteristics of the tumors. This study was performed retrospectively from
      February 1987 to August 2010. There were 95 male, and 76 female patients. Most of
      the patients complained of the painless and progressively enlarged mass in the
      preauricular area. Peak incidence of benign parotid gland tumor was at the fifth
      decade of life. In the malignant tumors, peak age in males was the eighth decade,
      and peak age in females was from the third to the fifth decade of life, which was
      relatively younger and has a broad range of spectrum. Pleomorphic adenoma was the
      most common benign tumor of the 93 cases (61.6%) followed by Warthin tumor,
      occurring in 20 cases (13.2%). Squamous cell carcinoma, reported in 6 cases
      (30%), is the most frequent. Mucoepidermoid carcinoma was the second leading
      tumor. In conclusion, parotid gland tumor incidence was found to be higher in
      males. Pleomorphic adenoma was the most commonly encountered type of parotid
      gland neoplasms, which is in agreement with findings from all of the published
      literature from all over world. In contrast to most of the previous studies,
      squamous cell carcinoma was the most frequent malignant tumor found. Based on the
      data in this study, it has significant clinical respect and is helpful in the
      management of parotid gland tumors in Orientals.

PMID- 22627433
TI  - Comparison of the effect of 2 hypotensive anesthetic techniques on early recovery
      complications after orthognathic surgery.
AB  - The aim of this study was to evaluate the recovery complications following the
      use of 2 anesthetic protocols in orthognathic surgery, namely, propofol with
      remifentanil and isoflurane with remifentanil. Sixty-two patients with American
      Society of Anesthesiologists physical status I were selected. All underwent
      bimaxillary orthognathic surgery. Propofol with remifentanil was used as an
      anesthesia in group 1 (n = 32), and isoflurane with remifentanil was used in the
      patients in group 2 (n = 30). Early recovery complications consisting of pain,
      postoperative nausea and vomiting (PONV), shivering, and agitation were evaluated
      and documented. The length of the operation and duration of recovery were
      documented for all patients. Analysis of the data demonstrated no relationship
      between age and recovery time (P > 0.05). Analysis of data with chi(2) and
      independent t-tests did not show any difference between the 2 groups with regard
      to pain, agitation, PONV, and shivering (P > 0.05). Logistic regression was used
      to evaluate the effect of the operation time on recovery complications. The
      analysis showed that pain and PONV were significantly higher in those who
      experienced a longer operation time. With increasing operation time longer than
      165 minutes, 64% of patients experienced pain, and 89% of them had PONV. General
      anesthesia can be provided via intravenously administered medications and/or
      inhaled volatile anesthetics. No significant difference in early recovery time
      was found in patients when either isoflurane or propofol was used to maintain the
      anesthesia. However, the length of the operation played a major role in
      increasing early recovery complications.

PMID- 22627435
TI  - Apert syndrome in a newborn infant without craniosynostosis.
AB  - Apert syndrome is a rare congenital disorder characterized by irregular
      craniosynostosis especially of the coronal suture. We report a case of Apert
      syndrome confirmed by molecular genetic analysis in a newborn infant, who did not
      have craniosynostosis at birth. Because this disturbance in osteogenesis may vary
      in timing and extent, we suggest that this diagnosis be considered even in the
      absence of this hallmark finding.

PMID- 22627436
TI  - Ascending necrotizing fasciitis of the face following odontogenic infection.
AB  - Necrotizing fasciitis (NF) of the face is a rare but extremely dangerous
      complication of dental infection associated with a nearly 30% mortality rate.
      This infection spreads rapidly along the superficial fascial planes of the head
      and neck and can lead to severe disfigurement. Reports in the literature of cases
      of NF of the face caused by dental infection are few. We report such a case in a
      36-year-old woman and review the current standards of diagnosis and management.
      The patient initially presented with pain and severe swelling in the left side of
      her face subsequent to a dental infection. The symptoms had progressed quickly
      and had not improved with administration of oral antibiotics in the outpatient
      setting. The patient had no palpable crepitus despite its classic association
      with NF. The infection also took a rare, ascending route of spread with
      involvement of the temporalis muscle. Cultures taken during debridement grew
      Streptococcus anginosus and Bacteroides. Biopsies of involved muscle showed
      histologic evidence of necrosis. Through early surgical intervention including
      aggressive debridement, and the adjunctive use of appropriate antibiotics, the
      patient recovered with minimal loss of facial mass and no skin loss. Although NF
      of the face is rare, the surgeon must maintain a high index of suspicion with any
      patient presenting after a dental infection with rapid progression of swelling
      and a disproportionate amount of pain that is unresponsive to antibiotics.

PMID- 22627437
TI  - Oral lesions in renal transplant.
AB  - To prevent rejection of kidney transplants, patients must be kept in
      immunosuppressive therapy for a long time, which includes the use of drugs such
      as cyclosporine, azathioprine, cyclophosphamide, and prednisone. The action of
      these drugs reduces the general immune response of transplant patients and thus
      increases their susceptibility to infections. Moreover, these drugs increase the
      potential of developing lesions. Therefore, oral hygiene in kidney transplant
      recipients contributes to maintenance of the transplanted organ and its function.
      Thus, an investigation of oral lesions could be counted as a notable work. The
      aim of this study was to investigate oral lesions in a group of 21 kidney
      transplant patients under immunosuppressive therapy attended during a 1-year
      period in the Nephrology Department of the Federal University of Sergipe, Brazil.
      Data related to sex, age, etiology of renal disease, types of renal transplant,
      time elapsed after transplantation, immunosuppressive treatment, use of
      concomitant agents, and presence of oral lesions were obtained. All patients
      received a kidney transplant from a living donor, and the mean
      posttransplantation follow-up time was 31.6 months; 71.5% used triple
      immunosuppressive therapy with cyclosporine A, azathioprine, and prednisone. Ten
      patients were also treated with calcium-channel blockers. Of the 21 transplant
      patients, 17 (81%) presented oral lesions. Gingival overgrowth was the most
      common alteration, followed by candidiasis and superficial ulcers. One case of
      spindle cell carcinoma of the lower lip was observed. Oral cavity can harbor a
      variety of manifestations related to renal transplantation under
      immunosuppressive therapy.

PMID- 22627438
TI  - Cervical spine in Treacher Collins syndrome.
AB  - Treacher Collins syndrome is a congenital syndrome with characteristic
      craniofacial malformations, which are well described in the literature. However,
      the presence of cervical spine dysmorphology in this syndrome has been minimally
      described. This study reviews cervical spine radiographs of 40 patients with
      Treacher Collins syndrome. In this sample, 7 of 40 patients displayed cervical
      spine anomalies, with 3 of these patients displaying multiple cervical spine
      anomalies. The patterns of spinal anomalies were variable, suggesting that the
      underlying genetic mutation has variable expressivity in cervical spine
      development as it does elsewhere in the craniofacial skeleton.

PMID- 22627439
TI  - Bioactive glass for alveolar ridge augmentation.
AB  - The restoration and recovery of the alveolar healing process are a challenge to
      dental surgeons to achieve satisfactory results at the osseointegration of
      implants and implant rehabilitation. Different operative technique and
      biomaterials are being used to reconstruct the framework of the alveolar process.
      One of the biomaterials used for this purpose is the bioactive glass. The aim of
      this study was to report clinical and histologic final results of 7 clinical
      reports of alveolar ridge augmentation using bioactive glass. Clinically,
      bioglass was able to maintain bone architecture of the alveolar bone and repaired
      satisfactory. Biopsy was performed on the histologic samples and showed bone
      formation in intimate contact to the particles of the biomaterial.

PMID- 22627440
TI  - Dental outcomes in computer-assisted orthognathic surgery.
AB  - The purpose of this study was to assess the effectiveness of computer-aided
      orthognathic surgery in reducing incisal overjet and establishing class I
      occlusion in subjects with dentofacial deformities. To address the research
      purpose, the investigators initiated a retrospective cohort study and enrolled a
      sample of subjects who underwent computer-assisted orthognathic surgery for
      dentofacial deformities. Two examiners assessed preoperative and postoperative
      lateral cephalometric radiographs for change in overjet after computer-assisted
      orthognathic surgery. Preoperative and postoperative occlusal photographs were
      then reviewed to assess for establishment of class I occlusion after computer
      assisted orthognathic surgery. Cohen kappa coefficient was used to assess for
      interrater agreement. A matched-pairs t-test was used to assess reduction in
      incisal overjet after computer-assisted orthognathic surgery. The sample was
      composed of 9 subjects who underwent computer-assisted surgery for dentofacial
      deformities. There was good interrater consistency for preoperative measurement
      of overjet (kappa = 0.7, P <= 0.001). There was fair interrater consistency for
      postoperative measurement of overjet (kappa = 0.4, P = 0 .02). Both examiners
      agreed on preoperative and postoperative assessments of occlusal photographs.
      There was a 3.4-mm reduction in incisal overjet after computer-assisted
      orthognathic surgery (P <= 0.001). Mean postoperative absolute overjet was 1.3
      mm. In subjects with dentofacial deformities, computer-aided orthognathic surgery
      was effective in reducing incisal overjet and establishing class I occlusion.

PMID- 22627441
TI  - Clinicopathologic features of dentigerous cysts in the maxillary sinus.
AB  - Dentigerous cyst (DC) in the maxillary sinus is extremely rare. This study
      evaluated the clinical features, etiologic factors, imaging, treatment, and signs
      and symptoms of this type of DC. Clinical symptoms, radiographic findings,
      surgical methods, and histopathologic findings of 4 patients with DCs in the
      maxillary sinus were evaluated. In addition, we reviewed the literature reports
      of DCs in the maxillary sinus over the past 40 years. Our 4 patients with DC in
      the maxillary sinus showed the following results: (1) all the patients were males
      at first 3 decades of age, (2) swelling and/or yellow-green pus discharges from
      pharyngeal cavity were common symptoms, (3) the involved teeth in the DC were the
      maxillary third molar teeth and supernumerary teeth, and (4) Caldwell-Luc
      approach was performed in these 4 patients. The patients with DC in the maxillary
      sinus should be evaluated thoroughly by extraoral and intraoral examinations,
      proper diagnostic imaging procedures, and pathologic examination to avoid
      misdiagnosis of maxillary sinusitis. The standard treatment for DC in the
      maxillary sinus is often removed by Caldwell-Luc approach. Furthermore,
      marsupialization or functional endoscopic sinus surgery may be performed because
      of the size, location of the cysts, or the age of the patients.

PMID- 22627442
TI  - Simulated fronto-orbital advancement achieves reproducible results in metopic
      synostosis.
AB  - BACKGROUND: Metopic synostosis results in trigonocephaly with bitemporal
      narrowing. Treatment involves differential fronto-orbital advancement, widening
      of the bitemporal region, and rounding the forehead. The purpose of this article
      was to implement three-dimensional surgical planning to treat metopic synostosis,
      including use of intraoperative templates, and to test the accuracy of the
      results. METHODS: This is a prospectively analyzed series of retrospective
      patients with metopic synostosis. Consecutive cases treated by the authors
      involving a simulated computer-aided planning session were reviewed. Demographic
      data were tabulated, and three-dimensional quantitative data reviewed.
      Measurements obtained included bifrontal angle, temporal advancement, and
      bitemporal distance and widening. Preoperative, simulated, and actual results
      were compared and analyzed using the t test. RESULTS: Five infants with metopic
      synostosis treated by this method were included (3 boys, 2 girls). The
      endocranial bifrontal anglechanged from 111.25 degrees  preoperatively to 148.58
      degrees  postoperatively (P = 0.0001) and simulated 145.62 degrees  (compared
      with actual 148.58) (P = 0.5099). The bitemporal distance preoperative averaged
      73.72mm, compared with actual of 89.78mm (P = 0.019), and was simulated to
      89.28mm (vs actual 89.78) (P = 0.8815). The surgically planned advancement and
      expansion were similar compared with actual (P = 0.591, 0.806, and 0.806),
      respectively. CONCLUSIONS: The results show that simulated surgical planning can
      accurately and reproducibly be translated to actual surgical outcome during
      fronto-orbital advancement for trigonocephaly. The treatment goals for metopic
      synostosis are conserved and effectively achieved, including lateral orbital
      advancement, widening of the endocranial bifrontal angle, bitemporal expansion,
      and rounding of the forehead.

PMID- 22627443
TI  - Contemporary techniques for the correction of temporal hollowing:  augmentation
      temporoplasty with the classic dermal fat graft.
AB  - INTRODUCTION: Temporal hollowing is a depression within the soft tissues
      overlying the temporal fossa, sometimes seen after surgical dissection for access
      to the facial skeleton. Surgeons have successfully used bone grafts,
      hydroxyapatite, methyl methacrylate, and autogenous tissue to correct the
      deformity. A systematic review of the literature demonstrated that the most
      popular technique for the correction of temporal hollowing seems to be the use of
      nonbiologic materials. These materials have been used successfully but are
      associated with some complications. There has been a growing experience with
      augmentation of the soft tissues of the temporal fossa using dermal fat grafts at
      our institutions, and this article describes this experience. METHODS: Two senior
      surgeons' recent experience with the correction of temporal hollowing was
      reviewed and analyzed. RESULTS: The retrospective review revealed 5 cases of
      temporal hollowing treated with dermal fat graft placement. Follow-up at 1 year
      revealed aesthetically pleasing results. CONCLUSIONS: A thorough understanding of
      temporal anatomy and conscious effort to respect structural integrity during
      dissection are essential in avoiding temporal hollowing. Sometimes, however, this
      deformity is impossible to avoid. In these patients, there are a number of
      options for correction. Open placement of the classic dermal fat graft is a
      technique that seems to offer good long-term aesthetic results.

PMID- 22627444
TI  - New aesthetic approach to carotid cavernous sinus fistula for coil embolization.
AB  - PURPOSE: Transvenous embolization has become the treatment of choice for carotid
      cavernous sinus fistula (CCSF). We report a case of coil embolization of CCSF
      using a superior ophthalmic vein (SOV) approach. METHODS: We have used the SOV
      approach on 5 patients with dural arteriovenous fistulas involving the cavernous
      sinus. Diagnostic facial contrast-enhanced computed tomography, brain magnetic
      resonance imaging, and contrast angiography and cerebral angiography revealed a
      CCSF. Fistula occlusion using an external SOV approach of CCSF was performed.
      RESULTS: Angiography performed on both sides demonstrated complete occlusion of
      the fistula. We had good result with coil embolization via SOV approach. We have
      a 100% success rate with no major complication. CONCLUSIONS: The coil
      embolization via SOV approach is a safe and effective treatment. The SOV can be
      channeled by allowing the insertion of detachable coils in the fistula. We
      suggest that there is need to training plastic surgeon to be experienced.

PMID- 22627445
TI  - Total auricular reconstruction after traumatic total amputation of the auricle.
AB  - We present a case of successful total auricular reconstruction after total
      amputation of the auricle. Owing to the severe damage to the auricular cartilage,
      replantation was not attempted; instead, for the next step of the reconstruction,
      severed superficial temporal artery and vein were anastomosed. At the second
      stage, total auricular reconstruction was planned. A huge temporoparietal fascial
      flap was used (based on STA/STV), which was used to cover the costal cartilage
      ear framework. This case suggests that, even for the total loss of the auricle,
      autogenous reconstruction can still be successfully done if a temporoparietal
      fascial flap is available.

PMID- 22627446
TI  - Forehead abscess caused by Klebsiella oxytoca with undiagnosed type 2 diabetes.
AB  - Klebsiella is an opportunistic pathogen that is known to cause septicemia,
      pneumonia, urinary tract infections, hepatobiliary tract infections, and soft
      tissue infections in patients who have severe underlying diseases or are under
      immunosuppression. Most Klebsiella species found are Klebsiella pneumoniae, and
      Klebsiella oxytoca is rarely cultured in humans. We report a case of a 48-year
      old man presenting with a soft fluctuating mass on his forehead. The lesion was
      an abscess, and percutaneous drainage yielded pus from which K. oxytoca was
      isolated. Parenteral levofloxacin was administrated leading to resolution of
      infection signs. Because of the rarity of the pathogen, evaluation for underlying
      illnesses was done, and the patient was diagnosed with type 2 diabetes mellitus.
      This is the first report of a patient with previously undiagnosed diabetes who
      was found with an extraorbital abscess caused by K. oxytoca, which we present
      with a review of diagnosis, pathogenesis, and treatment.

PMID- 22627447
TI  - Stensen duct relocation after cheek mucosa tumor resection.
AB  - Cheek mucosa cancer might surround Stensen meatus requiring preservation and
      relocation of the duct. Sialodochoplasty is necessary to avoid subsequent
      stricture, cheek swelling, and obstructive sequelae that could make following
      oncologic follow-up difficult. We report a simple successful technique of parotid
      duct cannulation and relocation in a 77-year-old woman who underwent cheek mucosa
      tumor resection for squamous cell carcinoma and free fasciocutaneous forearm
      reconstruction. Ability of milk clear saliva from the duct orifice after 6 weeks
      from surgery was assessed clinically, and no fistula or swelling was experienced.
      Stensen duct cannulation and relocation are a useful adjunctive procedure in the
      treatment of oral mucosa cancer, preserving salivary gland function while not
      compromising cancer resection.

PMID- 22627448
TI  - Closed reduction of fractured anterior wall of the frontal sinus using threaded K
      wires.
AB  - Classic approach of the anterior wall of frontal sinus fracture involves
      bicoronal or direct forehead incisions. However, these methods have some
      disadvantages, for example, paresthesia, scarring, and even alopecia. The purpose
      of this study was to introduce the simple and effective method of reduction of
      the anterior wall of frontal sinus fracture with threaded K-wires. Thirteen
      patients with fracture of the anterior wall of the frontal sinus underwent our
      method from December 2005 to September 2011. The distance of threaded K-wires was
      measured by facial computed tomography, and those marks were made directly on the
      threaded K-wires with an aseptic pencil. Closed reduction with these K-wires was
      tried carefully until a tolerable level was attained with digital palpation.
      Facial computed tomography was performed the following day for comparison. On
      postoperative day 7, following disappearance of swelling, the patient and the
      doctor mutually evaluated the outcome; both were satisfied with the results. The
      postoperative course was uneventful, without any complications. Unlike other
      methods, this method can guarantee a short operating time, effective reduction,
      and inconspicuous scar.

PMID- 22627449
TI  - Panconcha bullosa:  new definition in the literature.
AB  - Pneumatizated turbinates are named as concha bullosa in the literature. Concha
      bullosa is a frequently seen variation of the middle and superior turbinates. But
      concha bullosa in the inferior turbinate is rarely seen. But pneumatization of
      all turbinates in a person has not been published yet. Here is a 17-year-old
      adolescent girl who presented with concha bullosa in all turbinates.

PMID- 22627450
TI  - Preservation of the deep facial vein in reduction malarplasty.
AB  - PURPOSE: Many facial bone contouring surgeries, including reduction malarplasty,
      are performed in Asian countries to give the face an oval shape. When performing
      reduction malarplasty, a few large vessels can be injured, including the deep
      facial vein. The aim of this study was to determine the anatomy of the deep
      facial vein and to investigate the best method to prevent injury of deep facial
      vein during reduction malarplasty. PATIENTS AND METHODS: A retrospective chart
      review was performed for all patients who underwent reduction malarplasty with L
      shaped osteotomy between March 2009 and February 2010. We performed a chart
      review focusing on complications associated with bleeding, which result in an
      emergency operation. RESULTS: A total of 324 patients underwent reduction
      malarplasty with L-shaped osteotomy during the study period. In 2 cases, the deep
      facial vein was injured during vertical osteotomy at the posterior wall of the
      maxillary sinus, resulting in major bleeding. Because it was difficult to access
      the deep facial vein that lies just behind the posterior side of the maxillary
      sinus, the fixed free zygomatic bone segment had to be disassembled to access the
      vessels. CONCLUSIONS: In reduction malarplasty using L-shaped osteotomy, the
      subperiosteal dissection should be performed carefully and osteotomy should be
      performed cautiously not too deep to reach the periosteum of the posterior side
      of the maxillary sinus. The surgeon should consider the possibility of major
      bleeding because of injury to the deep facial vein, and it may be necessary to
      notify patients and explain this risk.

PMID- 22627451
TI  - Preoperative embolization for the treatment of cervical Castleman disease.
AB  - Castleman disease (CD) is a rare benign lymphoproliferative disorder commonly
      described as a hypervascular mass that causes progressive lymph node enlargement.
      Head and neck involvement occurs only in 15% to 20% of cases. The recommended
      treatment in solitary CD is radical resection. Few reports have described the use
      of angiographic study and preoperative embolization to minimize the
      intraoperative risk of hemorrhage. We report a clinical case of a solitary large
      painless, slow-growing mass located in the neck of a 34-year-old woman. Contrast
      enhanced computed tomographic and magnetic resonance imaging scan demonstrated a
      well-defined mass with internal calcifications and peripheral vessels located in
      the posterior cervical space, extending inferiorly to the supraclavicular space,
      which moderately enhanced after contrast administration. In the preoperative
      arteriography, a hypervascularized mass was identified, which mainly received an
      arterial supply from thyrocervical trunk. Successful embolization with polyvinyl
      alcohol microparticles was performed, resulting in a significant reduction of
      intraoperative bleeding, allowing a subsequently safe removal of the tumor.
      Histopathologic examination corresponded to hyaline vascular-type CD.

PMID- 22627452
TI  - Delayed free flap salvage after venous thrombosis.
AB  - The incidence of free flap failure is reported at 4% to 5%,but pedicle thrombosis
      occurs in a higher percentage, with the difference resulting from successful
      salvage of failing flaps. Often, these failures are attributed to postoperative
      venous thrombosis with salvage reported at 42%. The venous engorgement of the
      flap and the resulting microvascular changes lead to a more rapid and less
      reversible no-reflow phenomenon established within 6 hours. However, this report
      shows successful free flap salvage with thrombolytic drugs after 6 hours,
      highlighting that the mechanisms of free flap failure are still poorly
      understood.

PMID- 22627453
TI  - Infected sialocele:  complication in masseter reduction using radiofrequency
      coagulation.
AB  - Radiofrequency coagulation was introduced to reduce the volume of masseter
      muscle. Radiofrequency procedure causes focal necrosis in masseter muscles, which
      leads to muscle hypoplasia and a slender lower face. We present a case of a 24
      year-old woman who underwent radiofrequency coagulation to reduce masseter
      muscles. The patient experienced progressive erythematous swelling and noticed
      the mass around the right cheek 5 days after the procedure. On radiologic
      evaluation, a round cavity of 4-cm diameter containing air and fluid was
      observed. Incision and drainage was performed, and antibiotics were administrated
      intravenously. Blood-tinged purulent fluid was obtained, which was subsequently
      found to have a high amylase level. The swelling subsided, and there is no
      relapse up to 6 months after drainage. There are several complications of
      radiofrequency coagulation reported such as mucoserous fluid collections, late
      bleeding, infections, long-lasting pain, Stensen duct injury, facial nerve
      injuries, and limitation of temporomandibular joint movement. A well-designed
      operation plan and skilled technique are required to avoid these complications.

PMID- 22627454
TI  - Frontal linear scleroderma:  long-term result in volumetric restoration of the
      fronto-orbital area by structural fat grafting.
AB  - Frontal linear scleroderma (also known as "en coup de sabre") is a congenital
      deformity characterized by a linear band of atrophy and a furrow in the skin that
      occurs in the frontal or frontoparietal area. The authors present a case of a 34
      year-old woman with history of en coup de sabre. In different steps, volumetric
      restoration of the fronto-orbital region has been obtained by structural fat
      grafting technique. After 3 reconstructive surgeries, morphologic, functional,
      and aesthetic long-term results have been obtained.

PMID- 22627455
TI  - Treatment of malignant triton tumor in zygomatic region.
AB  - Malignant triton tumor (MTT) is extremely rare and supposed to be highly
      aggressive because of high propensity for local recurrence and metastasis. To
      date, only about 170 cases were reported in various body locations including
      trunks, maxillary sinus, neck, extremities, retroperitoneal, and so on. We
      present a case of MTT in the zygoma with good outcome. A 27-year-old male patient
      with progressive swelling and pain in the right zygoma was proved to have an MTT
      by biopsy. Radical resection accompanying postoperative radiotherapy was adopted,
      and then the soft and hard tissue defects were repaired by prosthesis. The
      patient recovered well and was satisfied with the facial contour. At 45-month
      follow-up, there was no recurrence or metastasis that occurred. According to
      literature review, one third of MTTs appeared in the head and neck regions and
      seem to have a better prognosis. Radical resection is the most important remedy,
      and adjuvant radiotherapy could be helpful. With early finding and effective
      treatments, satisfactory outcome could be achieved.

PMID- 22627456
TI  - Transient total facial nerve paralysis:  an unusual complication of transoral
      endoscopic-assisted management of subcondylar fracture.
AB  - Endoscopic-assisted repair of subcondylar fractures is an additional tool for
      management; however, there is a steep learning curve. Generally, this technique
      allows good visualization of the fracture site for reduction through an incision
      with an acceptable cosmetic result. Recently, the surgical techniques and
      technology as well as the indications for endoscopic facial fracture repair are
      in development; there are few available data in the literature regarding detail
      complications and recovery processes following endoscopic fracture treatment. The
      purpose of this article was to reveal unusual complication following endoscopic
      repair of subcondylar fracture in terms of radiographic, photographic, and
      recovering orders of the facial nerve and facial reanimations. In our case, no
      damage to the facial nerve was observed intraoperatively, but the patient had
      total facial paralysis, immediately postoperatively. At long-term follow-up, the
      facial nerve function was recovered well within 6 months. The authors consider
      that transoral endoscopic-assisted open reduction constitutes a valid alternative
      to a transcutaneous approach for the reduction and fixation of subcondylar
      fractures. It provides the benefits of open reduction and internal fixation
      without the permanent complications, such as facial nerve injury.

PMID- 22627457
TI  - An unusual presentation of presentation of a branchial cleft cyst.
AB  - Branchial cleft cysts are congenital anomalies that arise from the aberrant
      embryological development of the branchial apparatus. The location of a branchial
      cleft cyst is determined by which branchial cleft failed to obliterate during
      embryological development, with the second branchial cleft cyst being the most
      commonly recognized lesion. Although the most common location for branchial cleft
      cysts is between the external auditory canal and the level of the clavicle, the
      literature does describe unusual locations. We present a case a 15-year-old boy
      who had an enlarging lesion on his back that had been present since birth. A
      presumptive radiologic diagnosis of lymphangioma circumscriptum was made. Upon
      excision of the lesion and pathologic examination, it was determined to be a
      branchial cleft cyst. The patient had an uneventful postoperative course, and no
      recurrence was noted after a 2-year follow-up. Our clinical report demonstrates a
      lesion on the posterior thorax that proved to be a branchial cleft cyst and
      should always be part of the differential diagnosis for soft tissue masses of the
      thorax.

PMID- 22627458
TI  - Surprising cause of respiratory distress in child:  laryngeal leech.
AB  - Foreign body aspiration is a major problem that can cause respiratory distress
      and oral bleeding in a child. Leeches are rarely seen foreign bodies in the
      larynx. Generally, they live in springwater and can be aspirated by drinking.
      They can cause respiratory distress, oral bleeding, and anemia, if diagnostic
      process is delayed. When leeches are detected, urgent diagnosis and treatment are
      necessary. In this case, we present a 7-year-old child examined in the emergency
      service with these symptoms. A dark green living body in the larynx was detected
      and removed urgently under sedo-analgesia. The living body was seen as a leech
      that is 5 cm in length.

PMID- 22627459
TI  - Bilateral oncocytoma in the parotid gland.
AB  - Oncocytomas are rare tumors in the head and neck region. They occur commonly in
      salivary glands, especially in parotid glands. The prevalence is 0.5% to 1.2% in
      parotideal neoplasms. Oncocytomas rarely occur bilaterally. To our knowledge,
      only 20 cases were reported in the literature. A case with bilateral oncocytoma
      was presented with clinical, radiologic, and pathologic findings and treatment
      options in this study.

PMID- 22627460
TI  - A microfluidic-based frequency-multiplexing impedance sensor (FMIS).
AB  - We present a novel technology for the simultaneous and simple impedimetric
      screening of multiple microfluidic channels with only one electrode pair. We have
      exploited the frequency dimension to distinguish between up to three channels.
      Each 'sub-sensor' possesses its corresponding measurement frequency where the
      sample-specific dielectric properties can be probed. We have shown the validity
      of our frequency-multiplexing impedance sensor (FMIS) by comparison with
      conventional 'single sensors'. Our highly sensitive FMIS was proven suitable for
      life science applications through usage as a cell-based toxicology platform. We
      are confident that our technology might find great utility in parallelized cell
      based analysis systems as well as in biomedical devices where size limitations
      and spatially distributed probing are important parameters.

PMID- 22627461
TI  - Evaluation of smoking habits among Turkish family physicians.
AB  - Smoking is still a major public health problem in Turkey. It was aimed to
      investigate smoking prevalence and habits among Turkish family physicians. Cross
      sectional study among physicians working in primary care settings was
      established. A self-administered study survey was applied. The surveys of 1233
      family physicians were analyzed. The study included 704 (57.1%) male and 529
      (42.9%) female physicians. Mean age (SD) was 38.94 (7.01) years. The proportions
      of the current, the former and never smokers among family physicians were 34.1%,
      14.7% and 51.3%, respectively. Mean age (SD) of smoking initiation was 21.73
      (5.04) years. Mean duration (SD) of smoking use was 14.61 (7.29) years.
      Proportion of current smoker in male physicians was quite higher than in female
      counterparts (36.9% vs. 30.4%; p < 0.001). Mean age (SD) of smoking initiation in
      female was 21.42 (4.59) years, but in male was 22.33 (4.98) years (p = 0.36). In
      female physicians, mean age (SD) for quitting cigarette smoking was found higher
      than in male (35.85 (6.35) years vs. 33.09 (6.45) years; p = 0.004). No
      significant difference between nicotine dependence (mean score (SD) of 3.76
      (2.48) vs. 3.65 (2.82); p > 0.05) and mean (SD) unit of cigarette a day
      (18.34(6.03) vs. 17.17 +/- 6.79; p > 0.05) between genders was observed. The
      number of male physicians who started smoking before faculty was higher than
      female counterparts (15.5% vs. 8.6%; p = 0.023). In conclusion, the smoking
      prevalence among Turkish family physicians is considerably high. 

PMID- 22627462
TI  - CPR cardiopulmonary resuscitation or cerebral perfusion restoration.

PMID- 22627463
TI  - Assessment of beta-cell function in human patients.
AB  - This review focuses on the methods accessing beta-cell function. beta-cell
      failure is the critical step in the development of type 2 diabetes. Therefore,
      assessment of beta-cell function is an important part of the evaluation and
      treatment of diabetic patients. However, it is not easy because of complex
      interaction between multiple tissues. Several parameters should be considered,
      such as glucose level and insulin sensitivity of diverse insulin target tissues
      to assess beta-cell function. To overcome these difficulties, several invasive or
      non-invasive methods have been developed to assess beta-cell function for
      clinical or research purposes.

PMID- 22627465
TI  - Transient receptor potential ankyrin 1 as a target for perioperative pain
      management.

PMID- 22627464
TI  - Lipid emulsion infusion: resuscitation for local anesthetic and other drug
      overdose.

PMID- 22627466
TI  - Development of a carbon-14 labeling approach to support disposition studies with
      a pegylated biologic.
AB  - Although it is widely accepted that one can extend the pharmacokinetic half-life
      of a therapeutic protein by covalent conjugation with polyethylene glycol (PEG),
      the disposition properties of such biologics have not yet been fully evaluated.
      Therefore, a novel [14C]-labeling method was developed that can be applied to a
      biologic conjugated with PEG through a maleimide-cysteine reaction. The method
      was used to study the tissue and tumor distribution of a PEGylated Adnectin, a
      recombinant protein derived from the 10th type III domain of fibronectin, in nude
      mice bearing human xenograft tumors. The PEGylated Adnectin contained a 40-kDa
      branched PEG (P40B) that was labeled with [14C] at the linker region between the
      PEG and Adnectin, without compromising cellular activity and plasma half-life in
      mice. After a single intravenous or intraperitoneal dose (33 mg/kg, 1.7 MUCi per
      mouse) of [14C]-P40B-Adnectin, quantitative whole-body autoradiography analysis
      revealed that the liver had the highest uptake of the radioactivity among
      nontumor tissues, followed by the kidneys and lung. The muscle and brain showed
      the least penetration of the radioactivity among all tissues examined. In
      addition, the [14C]-P40B-EI-tandem penetrated into the tumor tissue, although the
      extent of accumulation was largely dependent on tumor type. Therefore, it was
      possible to assess the tissue distribution of a PEGylated biologic after it had
      been [14C] labeled using the novel method described herein.

PMID- 22627469
TI  - Transthyretin aggregates induce production of reactive nitrogen species.
AB  - BACKGROUND AND OBJECTIVE: Misfolded and aggregated transthyretins (agTTR)
      contribute to neurodegenerative amyloid diseases such as familial amyloid
      polyneuropathy and senile systemic amyloidosis. The neurotoxicity mechanisms of
      agTTR, however, are not well understood. In the current study, the possible
      contribution of reactive nitrogen species (RNS) to such mechanisms was
      investigated by examining agTTR-mediated changes in cellular RNS levels. METHODS
      AND RESULTS: The production of RNS was assessed through nitrate and nitrite
      assays in two human cell lines after exposure to agTTR (2.4 uM pre-aggregation
      concentration). In both epidermoid (A431) and schwannoma (sNF94.3) cell lines,
      agTTR induced significant increases in RNS (p < 0.05 relative to the same
      concentration of normal TTR, or no-TTR controls). Redox modulators such as
      apocynin (1-(4-hydroxy-3-methoxy-phenyl)ethanone) and L-NMMA (N(G)-monomethyl-L
      arginine) were tested for their effects on RNS production. These modulators
      decreased RNS production in both cell lines; although the effects of L-NMMA were
      statistically significant only in the schwannoma cells. Moreover, cells treated
      with agTTR exhibited decreases in metabolic activity relative to TTR- or non-TTR
      treated cells (p < 0.05) as assessed by reduction of MTT (3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide). CONCLUSION: The results provide novel
      evidence for involvement of RNS in pro-oxidative effects of agTTR in two
      different human cell lines, and show that agTTR can induce more generalized
      changes in cellular metabolic activity.

PMID- 22627470
TI  - Changes in von Willebrand factor-cleaving protease (ADAMTS-13) in patients with
      aortic stenosis undergoing valve replacement or balloon valvuloplasty.
AB  - It was the objective of this study to determine whether reduced cleavage of von
      Willebrand factor (VWF) multimers following aortic valve replacement (AVR) is a
      consequence of reduced shear stress or postoperative changes in VWF cleavage
      protease (ADAMTS-13) activity. Aortic stenosis (AS) may be complicated by
      acquired von Willebrand disease. Aortic valve replacement (AVR) corrects the
      associated haematologic abnormalities. We enrolled 114 patients with severe AS
      scheduled for either balloon aortic valvuloplasty (BAV; n=64) or AVR (n=50).
      Haematologic assessments of VWF levels and activity and ADAMTS-13 were performed
      before and 24 hours after valve intervention. The VWF:RCo to VWF:Ag ratio, a
      surrogate for large VWF multimer activity, increased by 37% (p < 0.0001) after
      AVR and by 10% (p = 0.0002) after BAV. ADAMTS-13 activity significantly decreased
      after AVR (579 +/- 127 to 468 +/- 135 ng/ml; p<0.0001), but not after BAV (484 +/
      153 to 529 +/- 185 ng/ml; p = 0.10). By multivariable analysis, the change in
      VWF:RCo ratio after AVR was more strongly associated with the fall in ADAMTS-13
      than with reduction of valve gradient; whereas the change in gradient better
      predicted the rise in VWF:RCo after BAV. In conclusion, both BAV and AVR reverse
      the haematological abnormalities of the acquired von Willebrand syndrome of AS
      and ADAMTS-13 levels decrease after AVR. These findings suggest that a portion of
      the haematologic benefit of AVR may be due to a postoperative decline in ADAMTS
      13 rather than solely to relief of AS as previously thought.

PMID- 22627471
TI  - An enantioenriched vanadium phosphonate generated via asymmetric chiral
      amplification of crystallization from achiral sources showing a single-crystal-to
      single-crystal dehydration process.
AB  - By using an asymmetrical 2-carboxyphenylphosphonate ligand (2-cpp(3-)), a chiral
      layered vanadium compound (VO)(3)(2-cpp)(2)(H(2)O)(6).H(2)O (1) is isolated. The
      bulk sample is enantioenriched due to symmetry breaking on crystallization.
      Partial release of the coordination water molecules upon heating leads to a
      single-crystal-to-single-crystal transformation to compound [(VO)(3)(2
      cpp)(2)(H(2)O)(4)] (1a) which is centrosymmetric.

PMID- 22627472
TI  - Increased vascular contractility and oxidative stress in beta2-adrenoceptor
      knockout mice: the role of NADPH oxidase.
AB  - BACKGROUND/AIMS: beta(2)-adrenoceptor (beta(2)-AR) activation induces smooth
      muscle relaxation and endothelium-derived nitric oxide (NO) release. However,
      whether endogenous basal beta(2)-AR activity controls vascular redox status and
      NO bioavailability is unclear. Thus, we aimed to evaluate vascular reactivity in
      mice lacking functional beta(2)-AR (beta(2)KO), focusing on the role of NO and
      superoxide anion. METHODS AND RESULTS: Isolated thoracic aortas from beta(2)KO
      and wild-type mice (WT) were studied. beta(2)KO aortas exhibited an enhanced
      contractile response to phenylephrine compared to WT. Endothelial removal and L
      NAME incubation increased phenylephrine-induced contraction, abolishing the
      differences between beta(2)KO and WT mice. Basal NO availability was reduced in
      aortas from beta(2)KO mice. Incubation of beta(2)KO aortas with superoxide
      dismutase or NADPH inhibitor apocynin restored the enhanced contractile response
      to phenylephrine to WT levels. beta(2)KO aortas exhibited oxidative stress
      detected by enhanced dihydroethidium fluorescence, which was normalized by
      apocynin. Protein expression of eNOS was reduced, while p47(phox) expression was
      enhanced in beta(2)KO aortas. CONCLUSIONS: The present results demonstrate for
      the first time that enhanced NADPH-derived superoxide anion production is
      associated with reduced NO bioavailability in aortas of beta(2)KO mice. This
      study extends the knowledge of the relevance of the endogenous activity of
      beta(2)-AR to the maintenance of the vascular physiology.

PMID- 22627474
TI  - Postoperative eye protection after cataract surgery.

PMID- 22627475
TI  - Macular pigment optical density in wet age-related macular degeneration among
      Indians.
AB  - PURPOSE: To estimate the value of macular pigment optical density (MPOD) in adult
      south Indian population with wet age-related macular degeneration (AMD). METHODS:
      A total of 33 patients with wet AMD and 29 age-matched controls >50 years of age
      underwent MPOD measurement with the macular densitometer. The patients were also
      tested for their dietary intake of carotenoids, smoking history, and lifetime UV
      exposure. RESULTS: The mean MPOD values in the Indian population with wet AMD was
      0.23 (95% CI: 0.18-0.29) vs control was 0.43 (95% CI: 0.37-0.49), P<0.0001, at
      0.5 degrees  eccentricity. Ex-smokers had a lower MPOD than non-smokers (0.16
      (0.09-0.23) vs 0.28 (0.22-0.34), P=0.026) and the lowest level of carotenoids
      intake had 48% lower MPOD than the highest level (0.14 (0.08-0.21) vs 0.33 (0.24
      0.43), P=0.012). There was no significant age-related decline or gender variation
      in MPOD. CONCLUSION: This study establishes the MPOD in adult Indian population
      with wet AMD, with a lack of macular pigment in association with wet AMD.

PMID- 22627477
TI  - Phase 1 dose-escalation study of a siRNA targeting the RTP801 gene in age-related
      macular degeneration patients.
AB  - BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics, and dose
      limiting toxicities of a single intravitreal (IVT) injection of PF-04523655, a 19
      nucleotide, O-methyl stabilized, double-stranded small interfering ribonucleic
      acid targeting the RTP801 gene in patients with neovascular age-related macular
      degeneration (AMD). METHODS: Prospective, phase 1, clinical multicentre trial,
      enrolled 27 patients with neovascular AMD unresponsive to prior treatment and
      best corrected visual acuity (BCVA) <= 20/200 in the study eye in stratum 1:
      (dose-escalating, open-label: 50 to 3000 MUg of PF-04523655) and 27 patients who
      had potential to benefit from therapy and BCVA of <= 20/100 and >= 20/800 in
      stratum 2 (parallel, masked study of 1000, 1500, 2250, and 3000 MUg of PF
      04523655). The primary outcome was safety and tolerability assessment as well as
      pharmacokinetic profiling following a single IVT injection of PF-04523655.
      RESULTS: Doses of PF-04523655 >= 400 MUg were generally detectable in the plasma
      at 1, 4, and 24 h post-injection. And all doses were below the lowest level of
      quantification by day 14. A single IVT injection of 50 to 3000 MUg of PF
      045237655 was generally safe and well tolerated over 24 months. There were no
      dose-limiting toxicities. CONCLUSION: A single IVT injection of PF-0523655 <=
      3000 MUg seems safe and well tolerated in eyes with neovascular AMD.

PMID- 22627478
TI  - 'Bilateral same-day cataract surgery should routinely be offered to patients' -
      yes.

PMID- 22627480
TI  - Entropion in children with isolated peripheral facial nerve paresis.
AB  - PURPOSE: Adults with facial nerve paresis (FNP) generally develop ectropion, but
      a recent report of children with syndromatic FNPs implies that entropion may be
      more common in this setting than ectropion. This study evaluates eyelid position
      and other periorbital changes in children with isolated, non-syndromatic FNP.
      METHODS: Charts were reviewed of 10 sequential children who presented to a major
      national eye referral centre with isolated FNP of variable aetiology. Severity of
      FNP was assessed according to the House-Brackmann scale. RESULTS: All 10 patients
      (4 males and 6 females; mean age at presentation, 4 years) had unilateral,
      isolated FNP. Mild lower-eyelid entropion was present in four patients, and
      severe lower-eyelid entropion required surgical correction in three patients. All
      patients had lower eyelid retraction (mean 2.3 mm) and lagophthalmos (mean 2.9
      mm). None had enophthalmos, lower eyelid ectropion, or brow ptosis. CONCLUSION:
      Unlike adults, children with isolated FNP seem prone to develop entropion rather
      than ectropion. Entropion reported previously in five syndromic children with FNP
      seems more likely related to patients' age than to their congenital syndromes.

PMID- 22627479
TI  - Evaluation of corpus geniculatum laterale and vitreous fluid by magnetic
      resonance spectroscopy in patients with glaucoma; a preliminary study.
AB  - PURPOSE: To determine whether metabolite changes at cellular level occur in
      vitreous and lateral geniculate body (LGB) in patients with glaucoma by magnetic
      resonance spectroscopy (MRS). METHODS: A total of 29 eyes of 29 patients with
      glaucoma, no existing ocular pathology and systemic disease (group 1), and 13
      eyes of 13 healthy individuals whose routine ophthalmological examinations were
      normal (group 2) were included in the study. Single-voxel MRS examination was
      performed by placing region of interest in vitreous and LGB. Glutamate-glutamine
      (Glx)/creatin (Cr) ratios and lactate peaks in the vitreous, and the Glx/Cr, N
      acetyl aspartate (NAA)/Cr, choline (Cho)/Cr ratios in the ipsilateral area of LGB
      were evaluated. RESULTS: A statistically significant difference was found between
      the two groups for the Glx/Cr ratio in both the vitreous and LGB (P=0.0001).
      There was no statistically significant difference between the two groups for the
      NAA/Cr, and Cho/Cr ratios in the LGB (P=0.108). A lactate peak was established in
      the vitreous of 11 glaucoma patients. CONCLUSION: Determining increased Glx/Cr
      ratios in both the vitreous and LGB of glaucoma patients, supports the theory of
      apoptosis in the etiopathogenesis of glaucoma. The MRS method, which can measure
      biochemical structures and metabolites of tissues, and also shows on a single
      spectrum, may be a new and non-invasive method for confirming the diagnosis of
      glaucoma and the role of apoptosis in the etiopathogenesis of glaucoma.

PMID- 22627481
TI  - 'Bilateral same-day cataract surgery should routinely be offered to patients' -
      no.

PMID- 22627482
TI  - Comment on 'effects of merogel coverage on wound healing and ostial patency in
      endonasal endoscopic dacryocytorhinostomy for primary chronic dacryocystitis'.

PMID- 22627483
TI  - Cytomegalovirus and eye.

PMID- 22627487
TI  - A microfluidic "baby machine" for cell synchronization.
AB  - Common techniques used to synchronize eukaryotic cells in the cell cycle often
      impose metabolic stress on the cells or physically select for size rather than
      age. To address these deficiencies, a minimally perturbing method known as the
      "baby machine" was developed previously. In the technique, suspension cells are
      attached to a membrane, and as the cells divide, the newborn cells are eluted to
      produce a synchronous population of cells in the G1 phase of the cell cycle.
      However, the existing "baby machine" is only suitable for cells which can be
      chemically attached to a surface. Here, we present a microfluidic "baby machine"
      in which cells are held onto a surface by pressure differences rather than
      chemical attachment. As a result, our method can in principle be used to
      synchronize a variety of cell types, including cells which may have weak or
      unknown surface attachment chemistries. We validate our microfluidic "baby
      machine" by using it to produce a synchronous population of newborn L1210 mouse
      lymphocytic leukemia cells in G1 phase.

PMID- 22627488
TI  - Chemotherapy-related thrombocytosis: does it increase the risk of
      thromboembolism?.
AB  - OBJECTIVES: Chemotherapy increases the risk of thromboembolism in patients with
      cancer. Although thrombocytopenia is a known side effect of chemotherapy,
      reactive thrombocytosis related to chemotherapy is uncommonly reported. The
      present study aimed to determine the incidence of gemcitabine-related
      thrombocytosis and the associated risk of thromboembolism. METHODS: Medical
      records of 250 consecutive patients with a malignant disease who received
      gemcitabine-based therapy were reviewed. A multivariate analysis was done to
      determine factors associated with thromboembolism. RESULTS: A total of 220
      eligible patients with a median age of 63 years (range 26-83) were identified. Of
      these 220 patients, 95% had advanced malignancy and 59% had received prior
      chemotherapy. A total of 69% of patients received a platinum combination. In all,
      46% patients experienced thrombocytosis following chemotherapy, with a median
      platelet count of 632 * 10(9)/l (range 457-1,385). Twenty-three of the 220
      patients experienced a vascular event within 6 weeks of treatment. Eleven
      patients with thrombocytosis experienced a vascular event compared with 10
      patients without thrombocytosis (not significant). On multivariate analysis,
      leukocytosis (odds ratio 5.8, 95% confidence interval 2.1-15.8) and comorbid
      illnesses (odds ratio 4.1, 95% confidence interval 1.4-12.6) were correlated with
      thromboembolism. CONCLUSIONS: Although gemcitabine-based therapy has been
      associated with an increased incidence of thrombocytosis, it does not increase
      the risk of thromboembolism in cancer patients. Leukocytosis and comorbid
      illnesses do increase the risk of thromboembolism.

PMID- 22627489
TI  - Esteem 2 middle ear implant: our experience.
AB  - INTRODUCTION: The Esteem is a totally implantable hearing system that uses
      piezoelectric technology. It is indicated in case of moderate to severe stable
      sensorineural hearing loss with a minimum discrimination score of 60% and a
      middle ear which is anatomically and functionally intact. Its two components
      (sensor and driver) are positioned and fixed in the mastoid cavity and coupled
      respectively to the incus body and capitulum with cement. STUDY DESIGN:
      Retrospective study. SETTINGS: Tertiary referral center. MATERIALS AND METHODS:
      Pure-tone average (PTA) gain in the implanted ear was calculated at 1, 2, and 4
      KHz, word recognition score (WRS) gain at 50 dB SPL, and average WRS (AWRS) gain
      at 40, 55, and 70 dB SPL. WRS was also evaluated in silence and noise. All
      patients were asked to fill in the abbreviated profile of hearing aid benefit
      (APHAB) questionnaire pre- and postoperatively as well as an Esteem
      questionnaire. RESULTS: Thirteen patients received implants between May 2008 and
      April 2010. Five minor complications occurred (1 temporary partial facial palsy,
      1 secondary healing difficulty, and 3 revision surgeries for poor and
      deteriorating functional results and progressive gain loss after use of a heart
      defibrillator). Two patients (15%) suffered major complications and their
      implants had to be removed 4 months postoperatively because of a Staphylococcus
      aureus wound infection. One patient underwent reimplantation 6 months later. Mean
      PTA gain was 25 +/- 11 dB, mean WRS gain at 50 dB SPL was 64 +/- 33%, and mean
      AWRS gain was 40 +/- 20%. WRS in silence and with a signal-noise ratio of 10, 0,
      and -5 dB was 91 +/- 11, 85 +/- 14, 71 +/- 19, and 64 +/- 30%, respectively. The
      APHAB questionnaire revealed 84% of satisfaction improvement compared to the
      previous classic hearing aid. CONCLUSION: The totally implantable hearing device
      Esteem 2 can offer good functional and satisfaction results. Careful selection of
      patients is required, however, based on hearing tests, exclusion of middle ear
      ventilation problems, and CAT-scan middle ear anatomy. Specific surgical training
      and experience are also needed. The implant is safe and only associated with
      classic auditory implant complications.

PMID- 22627490
TI  - Antituberculosis agent diaportheone B: synthesis, absolute configuration
      assignment, and anti-TB activity of its analogues.
AB  - First synthesis of diaportheone B, an antituberculosis agent isolated from
      endophytic fungus Diaporthe sp. P133 is reported using two complementary routes,
      a one step and a three-step sequence. The absolute configuration of diaportheone
      B was determined by using X-ray crystal structure analysis of its dibromo
      derivative. In addition, we have prepared several close analogues of diaportheone
      B and determined their anti-TB potential using Alamar-blue assay (H(37)Rv).

PMID- 22627491
TI  - Effects of an inclined walking surface and balance abilities on spatiotemporal
      gait parameters of older adults.
AB  - BACKGROUND AND PURPOSE: To date, few studies have investigated how walking
      patterns on inclines change in healthy older adults. The purpose of the study was
      to examine the effects of an inclined walking surface and balance abilities on
      various spatiotemporal gait parameters of healthy older adults. METHODS: Seventy
      eight self-reported independent community ambulators (mean age, 77.8 years; SD,
      4.8) participated in this study. After completing the Berg Balance Scale and
      Dynamic Gait Index (DGI), all participants were asked to walk on the GaitRite on
      level and inclined surfaces (10 degrees  slope). Dependent t tests were used to
      determine statistical significance between level and inclined surfaces for
      cadence, step length, velocity, and gait stability ratio (GSR). GSR is a measure
      of the degree of adaptation an individual makes to increase stability during gait
      derived from a ratio of cadence/velocity. A 2 2 analysis of variance was
      performed to determine differences in means among the higher-risk participants
      (as determined by the Berg Balance Scale and Dynamic Gait Index) comparing their
      level and incline walking patterns. The level of significance was set at P 0.05.
      RESULTS: During incline walking a significant decrease occurred in mean step
      length, 63.1(8.8) cm, P 0.001, mean cadence, 111.6 (8.9) step/min, P 0.01 and
      mean normalized velocity, 1.4 (0.23), P 0.001. However, mean GSR increased on
      inclines, 1.62 (0.22) steps/m, P 0.004. Main effects were evident for both
      walking surface and fall risk for all gait parameters tested. CONCLUSIONS:
      Healthy older adults adopt a more stable gait pattern on inclines decreasing
      velocity and spending more time in the double support despite the increased
      physiological demands to perform this task. Clear changes were evident between
      level and incline surfaces regardless of fall risk as defined by 2 different
      objective balance measures [corrected].

PMID- 22627494
TI  - Human skin keratinocytes, melanocytes, and fibroblasts contain distinct circadian
      clock machineries.
AB  - Skin acts as a barrier between the environment and internal organs and performs
      functions that are critical for the preservation of body homeostasis. In mammals,
      a complex network of circadian clocks and oscillators adapts physiology and
      behavior to environmental changes by generating circadian rhythms. These rhythms
      are induced in the central pacemaker and peripheral tissues by similar
      transcriptional-translational feedback loops involving clock genes. In this work,
      we investigated the presence of functional oscillators in the human skin by
      studying kinetics of clock gene expression in epidermal and dermal cells
      originating from the same donor and compared their characteristics. Primary
      cultures of fibroblasts, keratinocytes, and melanocytes were established from an
      abdominal biopsy and expression of clock genes following dexamethasone
      synchronization was assessed by qPCR. An original mathematical method was
      developed to analyze simultaneously up to nine clock genes. By fitting the
      oscillations to a common period, the phase relationships of the genes could be
      determined accurately. We thereby show the presence of functional circadian
      machinery in each cell type. These clockworks display specific periods and phase
      relationships between clock genes, suggesting regulatory mechanisms that are
      particular to each cell type. Taken together, our data demonstrate that skin has
      a complex circadian organization. Oscillators are present not only in fibroblasts
      but also in epidermal keratinocytes and melanocytes and are likely to act in
      coordination to drive rhythmic functions within the skin.

PMID- 22627495
TI  - Preoperative imaging for perforator flaps in reconstructive surgery: a systematic
      review of the evidence for current techniques.
AB  - BACKGROUND: Although preoperative imaging of perforator vasculature in planning
      microvascular reconstruction is commonplace, there has not been any clear
      demonstration of the evidence for this practice, or data comparing the many
      available modalities in an evidence-based approach. This article aims to provide
      an objective, evidence-based review of the literature on this subject. METHODS:
      The evidence supporting the use of various modalities of imaging was investigated
      by performing focused searches of the PubMed and Medline databases. The articles
      were ranked according to the criteria set out in March 2009 Oxford Centre for
      Evidence-Based Medicine definitions. Endpoints comprised objective outcome data
      supporting the use of imaging, including flap loss, unplanned returns to theater,
      operative time reduction, and surgeon-reported stress. RESULTS: The objective
      high level of evidence for any form of preoperative perforator imaging is low
      with only small number of comparative studies or case series investigating
      computed tomographic angiography (CTA), magnetic resonance angiography, handheld
      Doppler, color duplex, and classic angiography. Of all modalities, there is a
      growing body of level 2b evidence supporting the use of CTA. CONCLUSION: While
      further multicenter trials testing hard outcomes are needed to conclusively
      validate preoperative imaging in reconstructive surgery, sufficient evidence
      exists to demonstrate that preoperative imaging can statistically improve
      outcomes, and that CTA is the current gold standard for perforator mapping.

PMID- 22627493
TI  - Energy dysfunction in Huntington's disease: insights from PGC-1alpha, AMPK, and
      CKB.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease
      caused by a CAG trinucleotide expansion in the Huntingtin (Htt) gene. When the
      number of CAG repeats exceeds 36, the translated polyglutamine-expanded Htt
      protein interferes with the normal functions of many types of cellular machinery
      and causes cytotoxicity. Clinical symptoms include progressive involuntary
      movement disorders, psychiatric signs, cognitive decline, dementia, and a
      shortened lifespan. The most severe brain atrophy is observed in the striatum and
      cortex. Besides the well-characterized neuronal defects, recent studies showed
      that the functions of mitochondria and several key players in energy homeostasis
      are abnormally regulated during HD progression. Energy dysregulation thus is now
      recognized as an important pathogenic pathway of HD. This review focuses on the
      importance of three key molecular determinants (peroxisome proliferator-activated
      receptor-gamma coactivator-1alpha, AMP-activated protein kinase, and creatine
      kinase B) of cellular energy homeostasis and their possible involvement in HD
      pathogenesis.

PMID- 22627496
TI  - To everything there is a season: impact of seasonal change on admissions, acuity
      of injury, length of stay, throughput, and charges at an accredited, regional
      burn center.
AB  - PURPOSE: Although previous studies have investigated the impact of weather and
      temporal factors on incidence of trauma admissions, there is a paucity of data
      describing the effect of seasonal change on burn injury. The purpose of this
      study was to examine the impact of the changing seasons on admissions to and
      resource utilization at an accredited burn center, with the goal of optimizing
      patient throughput and matching supply with demand. METHODS: We performed a
      retrospective review of all burn admissions to an accredited, regional burn
      center, from Summer 2009 through Spring 2010. Patients were segregated into the
      seasonal cohorts of Summer, Fall, Winter, and Spring, based on admission date.
      Patient demographics included age, gender, mechanism of injury, and total body
      surface area (TBSA) injured. Main outcome measures included length of intensive
      care unit (ICU) stay, length of stay (LOS), and hospital charges, which served as
      a proxy for resource utilization (nursing, wound, and critical care; access to
      operating room (OR); inpatient rehabilitation). Groups were compared by T tests,
      with statistical significance assigned to P values <0.05. RESULTS: Seven hundred
      thirty patients were admitted to the burn center during this annual period, with
      a mean age of 31.6 years and a TBSA of 8.9%. Although Spring had the greatest the
      number of admissions at 219 (30%), patients from Summer and Winter had the
      largest burns, longest length of ICU and hospital stays, and highest hospital
      charges (P < 0.05). Furthermore, variability of these parameters, as measured by
      standard deviation, was greatest during Summer and Winter, serving to reduce
      throughput via uneven demand on resources. Highest throughput occurred during the
      Spring, which had the highest admission-to-LOS ratio. No differences were
      observed in age, gender, and incidence of electrical injuries, across the 4
      seasons. CONCLUSIONS: Summer and winter were the peak seasons of resource
      utilization at our burn center, in terms of length and variability of ICU and
      hospital stays, as well as total hospital charges. Such seasonal change may be
      related to acuity of burn injury but not number of burn admissions. To improve
      operational efficiency and maximize patient throughput, resource allocation
      should be structured to anticipate seasonal changes, so that supply of services
      matches demand.

PMID- 22627492
TI  - Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the
      neonatal brain: mechanisms and possible interventions.
AB  - Growing evidence of epidemiological, clinical and experimental studies has
      clearly shown a close link between adverse in utero environment and the increased
      risk of neurological, psychological and psychiatric disorders in later life.
      Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine,
      alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular
      and molecular levels to alter the brain development and result in programming of
      heightened brain vulnerability to hypoxic-ischemic encephalopathy and the
      development of neurological diseases in the postnatal life. The underlying
      mechanisms are not well understood. However, glucocorticoids may play a crucial
      role in epigenetic programming of neurological disorders of fetal origins. This
      review summarizes the recent studies about the effects of fetal stress on the
      abnormal brain development, focusing on the cellular, molecular and epigenetic
      mechanisms and highlighting the central effects of glucocorticoids on programming
      of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance
      the understanding of brain pathophysiology resulting from fetal stress and help
      explore potential targets of timely diagnosis, prevention and intervention in
      neonatal hypoxic-ischemic encephalopathy and other brain disorders.

PMID- 22627497
TI  - Melanoma arising on a scar 10 years after a burn: management and review of the
      literature.
AB  - We report a case of a melanoma arising after about 10 years after a burn injury.
      This is an uncommon example of a carcinogenetic event that could be prevented or
      diagnosed early. Usually, the mutagenic event clinically appears many years after
      the burn especially if it was not treated correctly with a careful surgical
      approach. The average time of latency could be found in literature as 46.5 years
      from the burn, whereas our case was only 10. A frequent and very long follow-up
      of the burn scars could represent a valid prophylactic option to avoid neoplastic
      proliferation if the tumor appears.

PMID- 22627498
TI  - Coculture of vascular endothelial cells and adipose-derived stem cells as a
      source for bone engineering.
AB  - The interaction between vascular endothelial cells (VECs) and osteoblasts (OBs)
      is the focus of this recent research. Vascular endothelial cells secrete bone
      morphogenetic protein, which promotes OB differentiation and stimulates OBs and
      their precursor cells to secrete vascular endothelial growth factor. Vascular
      endothelial growth factor is important in angiogenesis and angiopoiesis. Cloning
      studies have shown that adipose-derived stem cells (ADSCs) have the potential to
      differentiate into fat, bone, cartilage, and skeletal and smooth muscle cells,
      among others. Adipose-derived stem cells can express multiple growth factors,
      including vascular endothelial growth factor and hepatocyte growth factor. Our
      study examined the influence of coculturing VECs and ADSCs on osteogenic
      differentiation. Cord blood-derived VECs and ADSCs were isolated from rats and
      characterized with immunofluorescence staining and morphological observation.
      Coculture of third-generation ADSCs and VECs was induced for 6 weeks. Cell growth
      was analyzed using a modified MTT assay. Alkaline phosphatase (ALP) and
      osteocalcin (OC) was analyzed using immunofluorescence staining. When ADSCs and
      VECs were cocultured, the absorbance of cells gradually increased, reaching a
      peak on day 12. The highest absorbance was seen in a coculture system with a
      ratio of ADSCs and VECs of 1:1. The secretion of ALP and OC gradually increased
      in these cells and was significantly higher than controls (P < 0.01). Coculturing
      of ADSCs and VECs at a 1:1 ratio gave the highest secretion of ALP and OC at
      every time point, and was significantly higher than other groups (P < 0.01). Our
      results indicated that ADSCs can be induced to osteogenic differentiation by VECs
      in vitro, suggesting a coculture system of VECs and ADSC as a novel source of
      cells for bone engineering.

PMID- 22627501
TI  - Innovative use of an Amplatzer septal occluder for occlusion of a large right
      subclavian artery aneurysm and reconstruction of the posterior aortic arch wall.
AB  - PURPOSE: To highlight the efficacy of the Amplatzer septal occluder in
      endovascular exclusion of an aberrant right subclavian artery aneurysm and
      reconstruction of the posterior aortic arch wall for subsequent endovascular
      placement of a thoracic graft. CASE REPORT: A 73-year-old lady with prohibitive
      surgical risk was found to have a 35 * 39 mm aberrant right subclavian artery
      aneurysm as well as a 7.6 cm wide thoracic aortic aneurysm. Repair of both
      defects was performed endoluminally with the patient awake. An Amplatzer septal
      occluder was used for successful exclusion of the subclavian artery.
      Additionally, the device enabled reconstruction of the posterior aortic arch
      wall, thereby providing a landing zone for subsequent placement of a custom-made
      thoracic endograft. CONCLUSION: The Amplatzer septal occluder provides an
      innovative endovascular alternative for complex, large subclavian artery
      aneurysms.

PMID- 22627502
TI  - Hybrid porous tin(IV) phosphonate: an efficient catalyst for adipic acid
      synthesis and a very good adsorbent for CO2 uptake.
AB  - A new porous organic-inorganic hybrid tin phosphonate material has been
      synthesized hydrothermally, which shows a Brunauer-Emmett-Teller surface area of
      723 m(2) g(-1) and it adsorbs 4.8 mmol g(-1) CO(2) at 273 K and 5 bar pressure.
      The material also shows remarkable catalytic activity in one-pot liquid phase
      oxidation of cyclohexanone to adipic acid under eco-friendly conditions.

PMID- 22627503
TI  - Reactive leptin resistance and the profile of platelet activation in acute
      ischaemic stroke patients.
AB  - Leptin is an adipokine that in vitro enhances agonist-induced platelet
      aggregation and adipokine expression. Hyperleptinaemia represents a risk factor
      for cardiovascular disease. We conducted a prospective evaluation of the
      potential link between blood platelet activation and plasma leptin levels in post
      stroke patients. Using five-colour flow cytometry, the platelet surface
      expression of CD40L, CD62P, the subpopulations of monocyte-platelet aggregates
      and platelet-derived microparticles (PMPs) as well as the plasma leptin, soluble
      leptin receptor (sOb-R), leptin/sOb-R ratio, the plasma adiponectin, and
      leptin/adiponectin ratio were assessed in 98 stroke patients on the first (V0),
      10th (V1 ) and 90th (V2) day after stroke and once in 78 age-, gender- and
      vascular risk factor-matched disease controls. We demonstrated that at V0 leptin
      resistance, defined as leptin/sOb-R ratio, was higher than in the controls [1.1
      (0.5-1.8 vs. 0.5 (0.2-1.1); p=0.02]. After adjustment according to the factors
      which influence platelet activation, we confirmed the relationship between
      percentage of circulating PMPs and plasma leptin level (B=0.18; p=0.02) or the
      leptin/sOb-R ratio (B=0.23; p=0.02) in normal-weight subjects in the acute phase
      of stroke. No correlation could be demonstrated between the adipokine parameters
      and the percentage of monocyte-platelet aggregates or expression of platelet pro
      inflammatory glycoproteins. In conclusion, formation of PMPs on the first day
      following an ischaemic stroke shows a positive correlation with leptin levels and
      with resistance to leptin. Leptin level does not seem to affect the expression of
      platelet surface proinflammatory glycoproteins.

PMID- 22627504
TI  - Age at diagnosis of inflammatory bowel disease influences early development of
      colorectal cancer in inflammatory bowel disease patients: a nationwide, long-term
      survey.
AB  - BACKGROUND: Data on clinical characteristics of patients with inflammatory bowel
      disease (IBD)-related colorectal cancer (CRC) are scarce and mainly originate
      from tertiary referral centres. We studied patient and disease characteristics of
      IBD-related CRC in a nationwide IBD cohort in general hospitals. Main outcome
      parameters were time to develop CRC, and factors associated with early CRC
      development. METHODS: All IBD patients diagnosed with CRC between 1 January 1990
      and 1 July 2006 were identified using a nationwide automated pathology database
      (PALGA). Patient charts were assessed to confirm diagnosis and collect clinical
      data. Early CRC was defined as CRC diagnosed less than 8 years after IBD
      diagnosis. Statistical analysis was performed using descriptive statistics,
      independent t tests, binary logistic regression and Cox-regression analysis.
      RESULTS: Diagnosis of IBD-related CRC was confirmed in 251 patients (171
      ulcerative colitis, 77 Crohn's disease, 3 unclassified colitis), 161 males (64
      %). Median time from IBD diagnosis to CRC diagnosis was 12 years (IQR 4-20); 89
      patients (35 %) developed early CRC. Type of IBD, gender, concomitant PSC,
      pseudopolyps, extent of inflammation, and medication use were not related to
      early CRC (p > 0.05). IBD diagnosis at older age (HR for 10 years older age 2.25;
      95 % CI 1.92-2.63) was related to early CRC. Twenty-three patients (12 %) had
      been included in a surveillance programme prior to CRC diagnosis. Patients in the
      surveillance group had a significantly better tumor stage (p = 0.004).
      CONCLUSIONS: We emphasize the problem of a high proportion of IBD-associated CRCs
      developing before the recommended start of surveillance. Therefore, we suggest
      that older age at IBD onset could be an additional factor to start surveillance
      in IBD patients.

PMID- 22627505
TI  - Mathematical models for insulin secretion in pancreatic beta-cells.
AB  - Insulin secretion is one of the most characteristic features of beta-cell
      physiology. As it plays a central role in glucose regulation, a number of
      experimental and theoretical studies have been performed since the discovery of
      the pancreatic beta-cell. This review article aims to give an overview of the
      mathematical approaches to insulin secretion. Beginning with the bursting
      electrical activity in pancreatic beta-cells, we describe effects of the gap
      junction coupling between beta-cells on the dynamics of insulin secretion. Then,
      implications of paracrine interactions among such islet cells as alpha-, beta-,
      and delta-cells are discussed. Finally, we present mathematical models which
      incorporate effects of glycolysis and mitochondrial glucose metabolism on the
      control of insulin secretion.

PMID- 22627506
TI  - The theatricalization of death.
AB  - The essay analyzes anorexia as a theatrical performance, complete with its chosen
      acting school and particular dramatic features (plot, acting style, suspense
      establishing mechanisms and motifs).

PMID- 22627507
TI  - A three-dimensional model of thoughts: insight into depression.
AB  - Thought processing and mood regulation are closely linked, but existing
      classifications of mood disorders fail to recognize the complex interplay between
      these two clinical dimensions. Furthermore, existing classifications fail to
      account for the possibility that depression might be associated with an increased
      frequency of self-referential thoughts that could in some circumstances be
      related to creativity processes. Based on recent evidence from clinical
      phenomenology, experimental psychology and affective neuroscience, we propose a
      novel comprehensive theoretical framework that incorporates thought processing
      and emotional valence. This new taxonomy provides insights into the clinical
      understanding of the spectrum of mood disorders and accounts for the possibility
      of increased creativity in altered mood states.

PMID- 22627508
TI  - Chromatic dispersion measurements using a virtually referenced interferometer.
AB  - We present a technique for measuring the chromatic dispersion of short-length (<1
      m) optical devices using unbalanced spectral interferometry and a virtual
      reference path. The technique combines the speed and ease of measurement of
      unbalanced spectral interferometry with the accuracy of balanced spectral
      interferometry. We demonstrate measurement accuracy for group delay and the
      dispersion-length product of ~10(-3) ps/m (<0.0001% relative error) and ~10(-5)
      ps/m (<0.5% relative error), respectively. Measurement precision is demonstrated
      to be ~10(-5) ps/m (<0.15% relative deviation). We validate the technique via
      measurement of well-known dispersion standards.

PMID- 22627509
TI  - Targeted alteration of real and imaginary refractive index of biological cells by
      histological staining.
AB  - Various staining techniques are commonly used in biomedical research to
      investigate cellular morphology. By inducing absorption of light, staining dyes
      change the intracellular refractive index due to the Kramers-Kronig relationship.
      We present a method for creating 2D maps of real and imaginary refractive indices
      of stained biological cells using their thickness and absorptance. We validate
      our technique on dyed polystyrene microspheres and quantify the alteration in
      refractive index of stained biological cells. We reveal that specific staining of
      individual organelles can increase their scattering cross-section by orders of
      magnitudes, implying a major impact in the field of biophotonics.

PMID- 22627510
TI  - On the relative roles of higher-order nonlinearity and ionization in ultrafast
      light-matter interactions.
AB  - Far off-resonant ultrafast and nonlinear light-matter interactions are studied
      using a one-dimensional atomic model. Results from a pump-probe diagnostic reveal
      that any higher-order nonlinear refraction is masked by ionization-induced
      defocusing before it becomes significant. On the other hand, we show that
      signatures of a higher-order nonlinearity may still be manifest via low-order
      harmonics of the pump center frequency. Implications for filamentation of
      femtosecond pulses are pointed out.

PMID- 22627511
TI  - Hollow-core photonic crystal fiber based multifunctional optical system for
      trapping, position sensing, and detection of fluorescent particles.
AB  - We demonstrate a novel multifunctional optical system that is capable of
      trapping, imaging, position sensing, and fluorescence detection of micrometer
      sized fluorescent test particles using hollow-core photonic crystal fiber (HC
      PCF). This multifunctional optical system for trapping, position sensing, and
      fluorescent detection is designed such that a near-IR laser light is used to
      create an optical trap across a liquid-filled HC-PCF, and a 473 nm laser is
      employed as a source for fluorescence excitation. This proposed system and the
      obtained results are expected to significantly enable an efficient integrated
      trapping platform employing HC-PCF for diagnostic biomedical applications.

PMID- 22627512
TI  - Bending sensor based on intermodal interference properties of two-dimensional
      waveguide array fiber.
AB  - We propose a highly sensitive bending sensor based on the intermodal interference
      properties of a strongly coupled two-dimentional waveguide array fiber (WAF). The
      interference resonance peaks formed by the SMF-WAF-SMF Mach-Zehnder
      interferometer are intrinsically the result of interference between the LP(01)
      like supermode and other higher order supermodes, displaying supernormal
      sensitivity to bending in a wide curvature range. The bending sensitivity of the
      intermodal MZI is a quadratic function of curvature, and the resonance wavelength
      shift is up to 100 nm within a curvature range 0-10 m(-1). The fabrication
      reveals briefness, and temperature response shows little impact on the bend
      sensing precision. The high bending sensitivity and wide sensing range can make
      this device a candidate for bending discrimination and measurement in widespread
      areas.

PMID- 22627513
TI  - Simultaneous optically sectioned fluorescence and optical coherence microscopy
      with full-field illumination.
AB  - Full-field optical coherence microscopy (FF-OCM) and optically sectioned
      fluorescence microscopy are two imaging techniques that are implemented here in a
      novel dual modality instrument. The two imaging modalities use a broad field
      illumination to acquire the entire field of view without raster scanning. Optical
      sectioning is achieved in both imaging modalities owing to the coherence gating
      property of light for FF-OCM, and a structured illumination setup for
      fluorescence microscopy. Complementary image data are provided by the dual
      modality instrument in the context of biological tissue screening. FF-OCM imaging
      modality shows the tissue microarchitecture, while fluorescence microscopy
      highlights specific tissue features with cellular-level resolution by using
      targeting contrast agents. Complementary tissue morphology and biochemical
      features could potentially improve the understanding of cellular functions and
      disease diagnosis.

PMID- 22627514
TI  - Ultrathin fiber probes with extended depth of focus for optical coherence
      tomography.
AB  - We report on a novel scheme for extending the depth of focus (DOF) of ultrathin
      (125 MUm diameter) fiber probes for optical coherence tomography (OCT) using a
      simple phase mask consisting of graded-index (GRIN) fiber. The technique is
      compatible with existing all-in-fiber probe fabrication techniques, and our
      simulations show that it can provide a DOF gain of ~2 at a modest ~5 dB reduction
      of peak sensitivity. In a prototype device using commercially available GRIN
      fiber, a DOF gain of 1.55 is obtained, validated by beam profiling and OCT
      imaging.

PMID- 22627515
TI  - Deep-ultraviolet picosecond flat-top pulses by chirp-matched sum frequency
      generation.
AB  - Picosecond, flat-top, deep-UV pulses are needed to generate high-brightness
      electron beams to efficiently drive x-ray free electron lasers. Current metal
      photocathodes have low efficiency and therefore require high-energy pulses, and
      the generation of high-energy, flat-top pulses in the deep UV is still
      challenging. The low efficiencies of both the harmonic generation and deep-UV
      pulse shapers restrict the accessible pulse energy. Moreover, the acceptance
      bandwidth of the harmonic generation limits the minimum rise time of the flat-top
      profile. We present the generation of few-hundred microjoule, picosecond, deep-UV
      pulses using chirp-matched sum frequency generation. This scheme combined with IR
      spectral manipulation is a novel approach for deep-UV pulse shaping. It permits
      flat-top pulses with high energy and fast rise time, highly suited for high
      brightness photoelectron beam production.

PMID- 22627516
TI  - X-ray submicrometer phase contrast imaging with a Fresnel zone plate and a two
      dimensional grating interferometer.
AB  - The application of a two dimensional (2D) grating interferometer-Fresnel zone
      plate combination for quantitative submicron phase contrast imaging is reported.
      The combination of the two optical elements allows quick recovery of the phase
      shift introduced by a sample in a hard X-ray beam, avoiding artifacts observed
      when using the one dimensional (1D) interferometer for a sample with features
      oriented in the unsensitive direction of the interferometer. The setup provides
      submicron resolution due to the optics magnification ratio and a fine sensitivity
      in both transverse orientations due to the 2D analysis gratings. The method opens
      up possibilities for sub-micro phase contrast tomography of microscopic objects
      made of light and/or homogeneous materials with randomly oriented features.

PMID- 22627517
TI  - Noncontact all-optical measurement of corneal elasticity.
AB  - We report on a noninvasive and noncontact all-optical method to measure the
      elasticity of the cornea. We use a pulsed laser to excite surface acoustic waves
      (SAW) that propagate on the corneal surface, then use a phase-sensitive optical
      coherence tomography system to remotely record the SAWs from which the corneal
      elasticity is estimated. In addition, the system is able to provide real-time
      tomographic images of the cornea being examined, an important consideration for
      clinical studies. While precisely maintaining a range of intraocular pressures
      (IOP), a series of measurements is performed on ex vivo intact primate eyes. The
      measurement results not only demonstrate the feasibility of the proposed system
      to remotely measure the corneal elasticity, but also suggest a strong correlation
      between the corneal stiffness and the true IOP.

PMID- 22627518
TI  - Ultra-high efficiency multilayer blazed gratings through deposition kinetic
      control.
AB  - Diffraction efficiency of multilayer-coated blazed gratings (MBG) strongly
      depends on the perfection of the sawtooth-shaped layers in the overall composite
      structure. Growth of multilayers on sawtooth substrates should be carefully
      optimized to reduce groove profile distortion and, at the same time, to avoid
      significant roughening of multilayer interfaces. In this work, we report on a way
      to optimize growth of sputter-deposited Mo/Si multilayers on sawtooth substrates
      through variation of the sputtering gas pressure. We believe a new record for
      diffraction efficiency of 44% was achieved for an optimized MBG with groove
      density of 5250 lines/mm at the wavelength of 13.1 nm.

PMID- 22627519
TI  - Tomographic diffractive microscopy with a wavefront sensor.
AB  - Tomographic diffractive microscopy is a recent imaging technique that
      reconstructs quantitatively the three-dimensional permittivity map of a sample
      with a resolution better than that of conventional wide-field microscopy. Its
      main drawbacks lie in the complexity of the setup and in the slowness of the
      image recording as both the amplitude and the phase of the field scattered by the
      sample need to be measured for hundreds of successive illumination angles. In
      this Letter, we show that, using a wavefront sensor, tomographic diffractive
      microscopy can be implemented easily on a conventional microscope. Moreover, the
      number of illuminations can be dramatically decreased if a constrained
      reconstruction algorithm is used to recover the sample map of permittivity.

PMID- 22627520
TI  - Double shock dynamics induced by the saturation of defocusing nonlinearities.
AB  - We show that the saturation of defocusing nonlinearities leads to qualitative
      changes in the onset of wave breaking, determining double shock formation whose
      regularization occurs in terms of antidark solitons. In a given material, the
      crossover between different regimes can be controlled by changing the input
      intensity.

PMID- 22627521
TI  - Temperature dependence of Rb 5P fine-structure transfer induced by 4He
      collisions.
AB  - Employing ultrafast laser excitation and time-correlated single-photon counting,
      we have measured the fine-structure transfer between Rb 5P states induced by
      collisions with 4He buffer gas at temperatures up to 150  degrees C. The
      temperature dependence of the binary cross section agrees with earlier
      measurements. Our data show that the temperature dependence of the three-body
      rate is about the same as that of the binary rate. The three-body rate can be
      described as arising from the reduction of the rubidium fine-structure splitting
      due to nearby helium atoms.

PMID- 22627522
TI  - 66 W average power from a microjoule-class sub-100 fs fiber oscillator.
AB  - Performance scaling of passively mode-locked ultrashort-pulse fiber oscillators
      in terms of average power, peak power, and pulse energy is demonstrated. A very
      large-mode-area fiber laser in an all-positive group-velocity-dispersion ring
      cavity configuration with intracavity spectral filter, mode-locked by nonlinear
      polarization evolution, emits 66 W of average power at 76 MHz repetition rate,
      corresponding to 0.9 MUJ pulse energy. The pulses are dechirped to 91 fs outside
      the cavity with an average power of 60 W remaining after the compressor. The
      generated pulse peak power is as high as 7 MW.

PMID- 22627523
TI  - Leveraging bimodal kinetics to improve detection specificity.
AB  - Optical microcavities are high sensitivity transducers able to detect single
      nanoparticles and molecules. However, the specificity of detection is dependent
      on the availability of an appropriate targeting moiety with minimal cross
      reactivity. In the present work, an alternative approach is shown. Namely, using
      biotin-functionalized toroidal microcavities, the dissociation constant of biotin
      to two different streptavidin complexes (free and polystyrene bead) is
      determined. Based on the difference in affinity and in mass transport, the two
      complexes are identified from a mixture. By leveraging information in the binding
      site, improved specificity can be achieved.

PMID- 22627524
TI  - Reduction of pulse-to-pulse fluctuation in laser pulse energy using the optical
      Kerr effect.
AB  - An all-optical stabilization method of laser pulse energy is proposed using the
      optical Kerr effect (OKE). The method uses the OKE induced by a portion of the
      laser pulse as a power controller. The decrease (increase) in the throughput of
      the optical setup for OKE compensates for the increase (decrease) in pulse
      energy, thereby stabilizing the pulse-to-pulse fluctuation in pulse energy. The
      validity of this principle was proven by experiments with a femtosecond laser.

PMID- 22627525
TI  - Generalized effective mode volume for leaky optical cavities.
AB  - We show explicitly how the commonly adopted prescription for calculating
      effective mode volumes is wrong and leads to uncontrolled errors. Instead, we
      introduce a generalized mode volume that can be easily evaluated based on the
      mode calculation methods typically applied in the literature, and which allows
      one to compute the Purcell effect and other interesting optical phenomena in a
      rigorous and unambiguous way.

PMID- 22627527
TI  - Noise correlations in a doubly-resonant atomic optical parametric oscillator.
AB  - The simultaneous generations of bright Stokes and anti-Stokes fields are realized
      by using only one pump field in a Doppler-broadened atomic medium confined in an
      optical ring cavity. A vacuum-induced absorption phenomenon is also observed in
      such a system. By utilizing an external Fabry-Perot cavity to separate the Stokes
      and anti-Stokes fields, we investigate the noise correlation and anticorrelation
      properties between the Stokes, anti-Stokes, and the pump fields.

PMID- 22627526
TI  - Fiber four-wave mixing source for coherent anti-Stokes Raman scattering
      microscopy.
AB  - We present a fiber-format picosecond light source for coherent anti-Stokes Raman
      scattering microscopy. Pulses from a Yb-doped fiber amplifier are frequency
      converted by four-wave mixing (FWM) in normal-dispersion photonic crystal fiber
      to produce a synchronized two-color picosecond pulse train. We show that seeding
      the FWM process overcomes the deleterious effects of group-velocity mismatch and
      allows efficient conversion into narrow frequency bands. The source generates
      more than 160 mW of nearly transform-limited pulses tunable from 775 to 815 nm.
      High-quality coherent Raman images of animal tissues and cells acquired with this
      source are presented.

PMID- 22627528
TI  - Pulse inversion ultrasound modulated optical tomography.
AB  - Pulse inversion acoustic imaging is useful as it allows second harmonic imaging
      to be obtained with short acoustic pulses. This allows high axial resolution, but
      removes any overlap in the frequency spectra of fundamental and harmonic. We
      demonstrate pulse inversion ultrasound modulated optical tomography using an
      optical speckle based detection method. Inverted and non-inverted acoustic pulses
      combined with synchronized strobed illumination are applied to an optically
      scattering medium. Over the acquisition time of a camera, multiple pulses are
      summed and at the next frame the phase of the ultrasound is shifted by pi/2 and
      the process repeated. Combining the two frames allows a second harmonic signal to
      be obtained. A reduction in linewidth is observed (DC=9.26 mm, fundamental=4.02
      mm, second harmonic=2.43 mm) in line scans of optically absorbing objects
      embedded in a scattering medium (thickness=16 mm, scattering coefficient=2.3 mm(
      1), anisotropy factor=0.938).

PMID- 22627529
TI  - All-optical microwave bandpass filter and phase shifter using a broadband optical
      source and an optical phase modulator.
AB  - We propose a system that can perform microwave bandpass filtering and phase
      shifting simultaneously without redundant optical-electrical and electrical
      optical conversions. The principle is based on polarization-dependant phase
      modulation of a broadband optical source and the variable optical carrier time
      shift method. A single-bandpass microwave photonic filter with a central
      frequency of 10.8 GHz, a 3-dB bandwidth of 670 MHz, and a 360 degrees  phase
      tuning range is experimentally demonstrated. The capability of our configuration
      to implement wideband phase shifters is also verified.

PMID- 22627530
TI  - Q-switched thulium-doped photonic crystal fiber laser.
AB  - We report a novel, Tm-doped photonic crystal fiber (PCF) actively Q-switched
      oscillator that provides ~8.9 kW peak power with 435 uJ, 49 ns pulses at 10 kHz
      repetition rate at 2 MUm wavelength. This fiber has a mode-field area >1000 MUm2,
      the largest of any flexible PCF providing diffraction-limited beam quality to the
      best of our knowledge. As an application, the oscillator is used as pump to
      generate >350 nm broadening in ~50 m of SMF-28 fiber.

PMID- 22627531
TI  - Electromagnetic fields near plasmonic wedges.
AB  - The behavior of electromagnetic fields near the edge of a plasmonic wedge is
      investigated. We study the scattering properties, field divergence, and field
      enhancement near an Au wedge bounded by SiO2 upon illumination by TM-polarized
      light using hypersingular integral equations, as a function of wavelength, wedge
      angle, and angle of incidence. The transverse scattered field components show a
      convergent behavior at wavelengths approaching the surface plasmon energy
      asymptote (on the corresponding flat Au-SiO2 interface), and become strongly
      divergent at longer wavelengths. The computed divergence is compared with
      Meixner's theory and is found to be in good agreement over a restricted range of
      parameters.

PMID- 22627532
TI  - Tunable white luminescence and energy transfer in (Cu+)2, Eu3+ codoped sodium
      silicate glasses.
AB  - Luminescent properties of (Cu+)2, Eu3+ single-doped and codoped sodium silicate
      glasses were systematically investigated by excitation spectra, emission spectra,
      and decay curves. Due to the efficient energy transfer from (Cu+)2 pairs to Eu3+,
      varied hues from green to yellowish white and eventually to orange were generated
      by tuning the content of Eu3+. A perfect white-light emission with CIE
      coordinates (X=0.336,Y=0.346) was realized in (Cu+)2, Eu3+ and Ce3+ codoped
      samples. Our research indicates the potential application of (Cu+)2, Eu3+ codoped
      sodium silicate glasses for converting phosphors for UV LED chips to generate
      white LEDs.

PMID- 22627533
TI  - Carrier-envelope phase stable sub-two-cycle pulses tunable around 1.8 um at 100
      kHz.
AB  - We present a simple and efficient concept for the generation of ultrashort
      infrared pulses with passively stabilized carrier-envelope phase at 100 kHz
      repetition rate. The central wavelength is tunable between 1.6 and 2.0 um with
      pulse durations between 8.2 and 12.8 fs, corresponding to a sub-two-cycle
      duration over the whole tuning range. Pulse energies of up to 145 nJ are
      achieved. As a first application we measure the high nonlinearity of multiphoton
      photoemission from a nanoscale metal tip.

PMID- 22627534
TI  - Controlling the diffused nonlinear light generated in random materials.
AB  - We describe a method for shaping the wavefront of the second-harmonic light
      generated in nonlinear materials with a disordered structure using a spatial
      light modulator on the fundamental beam. We show that, for the case of a
      transparent strontium-barium niobate crystal with a random distribution of
      antiparallel domains, the speckle generation can be concentrated into a single
      spot.

PMID- 22627535
TI  - Polarization entanglement generation at 1.5 MUm based on walk-off effect due to
      fiber birefringence.
AB  - In this Letter, a linear scheme to generate polarization entanglement at 1.5 MUm
      based on commercial polarization maintained dispersion shifted fiber (PM-DSF) is
      proposed. The birefringent walk-off effect of the pulsed pump light in the PM-DSF
      provides an effective way to suppress the vector scattering processes of
      spontaneous four-wave mixing. A 90 deg offset of fiber polarization axes is
      introduced at the midpoint of the fiber to realize the quantum superposition of
      the two correlated photon states generated by the two scalar processes on
      different fiber polarization axes, leading to polarization entanglement
      generation. Experiments of the indistinguishable property on single-side and two
      photon interference in two nonorthogonal polarization bases are demonstrated. A
      two-photon interference fringe visibility of 89+/-3% is achieved without
      subtracting the background counts, demonstrating its great potential in
      developing highly a efficient and stable fiber based polarization-entangled
      quantum light source at the optical communication band.

PMID- 22627536
TI  - Femtosecond laser-assisted etching of three-dimensional inverted-woodpile
      structures in fused silica.
AB  - Three-dimensional inverted-woodpile (WP) structures were embedded in a
      microchannel by femtosecond laser direct-writing of fused silica followed by
      chemical etching with diluted hydrofluoric acid. We show the hole size is
      linearly dependent on laser-scanning depth for various pulse energies, permitting
      the control of laser exposures to facilitate close 5 um periodic packing of
      uniform microcapillary arrays. Exposure compensation for depth-dependent etching
      rate and optical beam aberrations yielded stable and crack-free uniform inverted
      WP structures. The direct formation of the inverted-WP structure together with
      microchannels in an all-fused silica substrate, offers chemical stability and
      inertness, and biocompatibility to be exploited as new microfluidic systems for
      chromatography and electro-osmotic pumps.

PMID- 22627537
TI  - Ultrabroadband supercontinuum generation in a CMOS-compatible platform.
AB  - We demonstrate supercontinuum generation spanning 1.6 octaves in silicon nitride
      waveguides. Using a 4.3 cm-long waveguide, with an effective nonlinearity of
      gamma=1.2 W(-1) m(-1), we generate a spectrum extending from 665 nm to 2025 nm
      (at -30 dB) with 160 pJ pulses. Our results offer potential for a robust,
      integrated, and low-cost supercontinuum source for applications including
      frequency metrology, optical coherence tomography, confocal microscopy, and
      optical communications.

PMID- 22627538
TI  - Single-pulse coherent diffraction imaging using soft x-ray laser.
AB  - We report a coherent diffraction imaging (CDI) using a single 8 ps soft x-ray
      laser pulse at a wavelength of 13.9 nm. The soft x-ray pulse was generated by a
      laboratory-scale intense pumping laser providing coherent x-ray pulses up to the
      level of 10(11) photons/pulse. A spatial resolution below 194 nm was achieved
      with a single pulse, and it was shown that a resolution below 55 nm is feasible
      with improved detector capability. The single-pulse CDI might provide a way to
      investigate dynamics of nanoscale molecules or particles.

PMID- 22627539
TI  - Compact, highly efficient ytterbium doped bismuthate glass waveguide laser.
AB  - Laser slope efficiencies close to the quantum defect limit and in excess of 78%
      have been obtained from an ultrafast laser inscribed buried channel waveguide
      fabricated in a ytterbium-doped bismuthate glass. The simultaneous achievement of
      low propagation losses and preservation of the fluorescence properties of
      ytterbium ions is the basis of the outstanding laser performance.

PMID- 22627540
TI  - Optical trapping of gold nanoparticles by cylindrical vector beam.
AB  - Optical trapping of gold nanoparticles is experimentally demonstrated using
      radially and azimuthally polarized beams. The transverse optical trapping
      stiffness of gold nanoparticles is measured. The radially polarized beam exhibits
      a higher trapping efficiency than the azimuthally polarized beam and the Gaussian
      beam. The transverse stiffness of particles with different diameters is measured
      experimentally and calculated via the discrete-dipole approximation method, and
      good agreement between theory and experiment is found.

PMID- 22627541
TI  - Production of optical notch filters with fine parameter control using regenerated
      fiber Bragg gratings.
AB  - A new method to create a controlled notch filter for attenuation of signals based
      on regenerated fiber Bragg gratings is experimentally demonstrated. A fine
      adjustment of the notch depth is achieved by controlling the time of regeneration
      phenomenon in strongly saturated Bragg gratings written in standard ITU G.652
      single-mode fiber. This method can used to produce tailored notch filters for
      several photonic applications, such as optical RF filtering, subcarrier
      processing or radio over fiber systems.

PMID- 22627542
TI  - Instabilities in quantum-dot spin-VCSELs.
AB  - A modified spin-flip model is used to investigate the stability of optically
      pumped quantum-dot spin-vertical cavity surface-emitting lasers. in terms of pump
      intensity and polarization. The stability maps exhibit pronounced polarization
      switching in the stable regions. Periodic oscillations in unstable regions are
      attributed to competition between spin relaxation and birefringence.

PMID- 22627543
TI  - Stroboscopic supercontinuum white-light interferometer for MEMS characterization.
AB  - We used a supercontinuum-based scanning white-light interferometer to
      characterize the oscillation of a MEMS device. The output of a commercially
      available supercontinuum light source (FiberWare Ilum II USB) was modulated to
      achieve stroboscopic operation. By synchronizing the modulation frequency of the
      source to the sample oscillation, dynamic 3-D profile measurements were recorded.
      These results were validated against those obtained with a white light LED setup.
      The measured maximum deflection of a 400*25*4 MUm(3) microbridge driven with 0
      6.8 V sinusoidal voltage at 10 Hz was 1.42+/-0.03 MUm (supercontinuum), which
      agreed with the LED measurement. The method shows promise for characterization of
      high-frequency MEMS devices.

PMID- 22627544
TI  - Water vapor concentration measurement in air using filament-induced fluorescence
      spectroscopy.
AB  - Water vapor fluorescence in air induced by femtosecond laser filaments was
      systematically investigated. The fluorescence signal intensity was found to be
      linearly proportional to the water vapor concentration, which opens up the
      possibility of absolute humidity measurements, even remotely.

PMID- 22627545
TI  - Four-step pulses of fractional-order surface plasmons.
AB  - The 0-order transmission of a 1D metallic grating, on a high-resistivity silicon
      wafer in optical contact with a silicon plate, has been characterized by
      terahertz time-domain spectroscopy with subpicosecond resolution over a 400 ps
      scan range. Two new long-time-delay, powerful pulses are observed after the
      second reflected pulse. In the frequency domain, these two strong and fast
      ringing structures correspond to the bandwidth ranges between the [0, 1] and [0,
      2] surface plasmon modes and the range above [0, 2], respectively. A physical
      optics ray analysis provides an intuitive understanding of these new four-step
      (reflection, diffraction, total reflection, and diffraction) pulses, caused by
      fractional-order surface plasmon type beam coupling.

PMID- 22627546
TI  - Experimental demonstration of joule-level non-collinear optical parametric
      chirped-pulse amplification in yttrium calcium oxyborate.
AB  - In this Letter, we report on what is, to our knowledge, the first experimental
      demonstration of yttrium calcium oxyborate (YCOB) for joule-level and broadband
      non-collinear optical parametric chirped-pulse amplification centered at 800 nm.
      Based on a Ti:sapphire chirped-pulse amplification front end, an amplified signal
      energy of 3.36 J was generated with a pump of 35 J in the crystal. Compressed
      pulse duration of 44.3 fs, with a bandwidth of 49 nm, was achieved. The results
      confirm that YCOB crystal is another potential alternative as a final amplifier
      besides Ti:sapphire in a petawatt laser at 800 nm.

PMID- 22627547
TI  - Anderson cross-localization.
AB  - We report Anderson localization in two-dimensional optical waveguide arrays with
      disorder in waveguide separation introduced along one axis of the array, in an
      uncorrelated fashion for each waveguide row. We show that the anisotropic nature
      of such disorder induces a strong localization along both array axes. The degree
      of localization in the cross-axis remains weaker than that in the direction in
      which disorder is introduced. This effect is illustrated both theoretically and
      experimentally.

PMID- 22627548
TI  - Modeling quantitative phase image formation under tilted illuminations.
AB  - A generalized product-of-convolution model for simulation of quantitative phase
      microscopy of thick heterogeneous specimen under tilted plane-wave illumination
      is presented. Actual simulations are checked against a much more time-consuming
      commercial finite-difference time-domain method. Then modeled data are compared
      with experimental measurements that were made with a quadriwave lateral shearing
      interferometer.

PMID- 22627549
TI  - Silicon slow-light-based photonic mixer for microwave-frequency conversion
      applications.
AB  - We describe and demonstrate experimentally a method for photonic mixing of
      microwave signals by using a silicon electro-optical Mach-Zehnder modulator
      enhanced via slow-light propagation. Slow light with a group index of ~11,
      achieved in a one-dimensional periodic structure, is exploited to improve the
      upconversion performance of an input frequency signal from 1 to 10.25 GHz. A
      minimum transmission point is used to successfully demonstrate the upconversion
      with very low conversion losses of ~7 dB and excellent quality of the received
      I/Q modulated QPSK signal with an optimum EVM of ~8%.

PMID- 22627550
TI  - Color lensless digital holographic microscopy with micrometer resolution.
AB  - Color digital lensless holographic microscopy with micrometer resolution is
      presented. Multiwavelength illumination of a biological sample and a posteriori
      color composition of the amplitude images individually reconstructed are used to
      obtain full-color representation of the microscopic specimen. To match the sizes
      of the reconstructed holograms for each wavelength, a reconstruction algorithm
      that allows for choosing the pixel size at the reconstruction plane independently
      of the wavelength and the reconstruction distance is used. The method is
      illustrated with experimental results.

PMID- 22627551
TI  - Multistep quadratic cascading in broadband optical parametric generation.
AB  - We theoretically and experimentally investigate multistep parametric processes in
      broadband optical parametric generators (OPGs) based on periodically poled 1 mol.
      % MgO-doped stoichiometric LiTaO3. We demonstrate that parametric collateral
      processes may deplete or enhance spectral portions of the OPG output, depending
      on pump pulse duration.

PMID- 22627552
TI  - Wavelength dependence of focusing properties of two-dimensional photonic
      quasicrystal flat lens.
AB  - We investigated the wavelength dependence of the focusing properties of a
      germanium-cylinder-based two-dimensional (2D) decagonal Penrose-type photonic
      quasicrystal (PQC) flat lens for the first time, to the best of our knowledge. We
      found that near the second bandgap and in the high-frequency side (between the
      bandgap boundary and the first light intensity peak) of the pass band, the flat
      lens can exhibit a focusing effect for a point light source and that the focusing
      wavelengths can directly be drawn from the photonic band structure. For all the
      focusing wavelengths, the summation of the object distance and the image distance
      is less than the thickness of the flat lens when the object distance is half the
      thickness of the flat lens. As the wavelength increases, the image distance, the
      image quality, and the effective refractive index of the flat lens increase,
      whereas the image power of the point light source decreases. The effective
      refractive index of the flat lens is less than -1.

PMID- 22627553
TI  - Entanglement of two spatially separated qubits via correlated photons.
AB  - We show that a high degree of steady-state entanglement between two spatially
      separated and initially uncoupled qubits can be achieved via interaction with a
      quantized squeezed field in a cavity. The cavity field induces two-photon
      coherence, which is crucial in creating entanglement between the qubits. Optimum
      entanglement is obtained when the less dissipative qubit is incoherently pumped
      while the other dissipates the excitation. Given the current state-of-the-art in
      cavity quantum electrodynamics and squeezed light sources, our scheme presents an
      effective way for light-to-matter entanglement transfer.

PMID- 22627554
TI  - Sending femtosecond pulses in circles: highly nonparaxial accelerating beams.
AB  - We use caustic beam shaping on 100 fs pulses to experimentally generate
      nonparaxial accelerating beams along a 60 degrees  circular arc, moving laterally
      by 14 um over a 28 um propagation length. This is the highest degree of
      transverse acceleration reported to our knowledge. Using diffraction integral
      theory and numerical beam propagation simulations, we show that circular
      acceleration trajectories represent a unique class of nonparaxial diffraction
      free beam profile which also preserves the femtosecond temporal structure in the
      vicinity of the caustic.

PMID- 22627555
TI  - Microfluidic sorting with blinking optical traps.
AB  - It is shown that by appropriately choosing the periodicity of a blinking optical
      trap only larger sized colloidal spheres can be selectively trapped out of a
      mixed population. This happens because smaller sized, more agile, spheres escape
      out of the trap volume during the off period of the trap beam. Therefore, by
      scanning an array of blinking traps over a mixed sample, bigger spheres can be
      forced to move with the traps and eventually could be taken to the output side.
      Experimental demonstration of sorting between 1 um and 2 um diameter silica
      spheres is presented.

PMID- 22627556
TI  - Extraordinary optical transmission: coupling of the Wood-Rayleigh anomaly and the
      Fabry-Perot resonance.
AB  - In this Letter, we demonstrate for the first time that by combining the effects
      of the Wood-Rayleigh anomaly (WRA) and the Fabry-Perot (FP) resonance,
      transmission efficiencies of one-dimensional metallo-dielectric gratings on
      substrates can be significantly improved compared to when these two phenomena
      work separately. Results of combining the WRA and the FP resonance can be
      utilized to eliminate the necessity of using the index matching technique and the
      core-shell structure for enhancing the performance of extraordinary optical
      transmission devices. Further, the outcomes of combining the WRA and the FP
      resonance can elucidate some of the unexplained results in the literature.

PMID- 22627557
TI  - Microelectromechanical-systems-driven two-layer rotary-blade-based adjustable
      iris diaphragm.
AB  - We report a miniature adjustable multi-blade iris diaphragm driven by
      microelectromechanical-systems-based electrostatic rotary microactuators. A proof
      of-concept device is designed and fabricated using a silicon-on-insulator
      micromachining process. The diameter of the developed iris diaphragm aperture is
      experimentally demonstrated to be able to adjust from 0.45 to 1.56 mm. When used
      in a miniature camera lens system, the current prototype device is capable of
      providing an adjustment range of more than three full f/stops.

PMID- 22627559
TI  - Analysis of an ultra-compact wavelength filter based on hybrid plasmonic
      waveguide structure.
AB  - In this letter, we propose and analyze an ultra-compact wavelength filter on
      silicon-based hybrid plasmonic waveguides, which confines light in a nanometeric
      silica dioxide layer between the silicon substrate and metal cap. The filter
      consists of a stub structure coupled to a straight waveguide. The three
      dimensional finite-difference time-domain (FDTD) method is applied to calculate
      the spectral responses of such devices. Similar resonant behaviors are obtained
      since those devices are based on two-dimensional Metal-Insulator-Metal waveguide
      structure. Results also show that by adding stubs and tuning the distance between
      stubs can further improve the device's performance and shape the spectral
      response to some extent.

PMID- 22627558
TI  - Plasmonic optical trap having very large active volume realized with nano-ring
      structure.
AB  - The feasibility of using gold nano-rings as plasmonic nano-optical tweezers is
      investigated. We found that at a resonant wavelength of lambda=785 nm, the nano
      ring produces a maximum trapping potential of ~32k(B)T on gold nanoparticles. The
      existence of multiple potential wells results in a very large active volume of
      ~10(6) nm(3) for trapping the target particles. The report nano-ring design
      provides an effective approach for manipulating nano-objects in very low
      concentration into the high-field region and is well suited for integration with
      microfluidics for lab-on-a-chip applications.

PMID- 22627560
TI  - Polarization-multiplexed vibrational sum frequency generation for comprehensive
      simultaneous characterization of interfaces.
AB  - We describe a novel three-pulse experimental arrangement for the simultaneous
      generation and subsequent resolution of all four electric-dipole allowed
      vibrational sum frequency generation polarization combinations. For
      noncentrosymmetric and achiral systems, this represents full characterization of
      all symmetry-allowed elements of the second-order susceptibility, providing a
      comprehensive intensity level assessment of the system under study. By measuring
      all relevant signals simultaneously, this approach enables assessment of
      molecular orientation and structure in dynamic, temporally evolving systems that
      were previously inaccessible by means of sequentially scanned acquisition of the
      individual tensor elements.

PMID- 22627561
TI  - Recovery of partially occluded objects by applying compressive Fresnel
      holography.
AB  - A compressive Fresnel holography approach is suggested for the recovery of
      partially occluded objects. Reconstruction guarantees are analyzed and the
      effectiveness of the method is demonstrated using simulations and an experimental
      result showing the reconstruction of a partially occluded resolution chart.

PMID- 22627562
TI  - Bayesian compressive optical imaging within the Rytov approximation.
AB  - Within the range of validity of the Rytov approximation (RA), an innovative
      Bayesian compressive sensing (BCS) inverse scattering technique is developed.
      Potentialities and limitations of the BCS-RA method are validated through
      numerical experiments and representative results are discussed.

PMID- 22627563
TI  - Circular grating waveguide structures for intracavity generation of azimuthal
      polarization in a thin-disk laser.
AB  - We report on the generation of beams with azimuthal polarization using resonant
      grating waveguide structures (GWSs) inside an Yb:YAG thin-disk laser (TDL)
      oscillator. Two different GWS concepts were used to select the polarization of
      the emitted beam. The first uses the resonant reflection principle, and the
      second is based on the leaky-mode approach already reported in our previous work.
      Up to 93 W and 103 W of output power were extracted from a TDL with an optical
      efficiency, eta(oo), of 36.2% and 40.1% using the first and the second
      approaches, respectively. In both cases, a pure azimuthal polarization and a beam
      quality factor, M2, of about 2.2 were measured. The design, fabrication, and
      different experimental results, as well as the laser performances for both GWSs,
      are discussed in the present Letter.

PMID- 22627564
TI  - 18 W single-stage single-frequency acoustically tailored Raman fiber amplifier.
AB  - A single-mode polarization-maintaining fiber doped to increase the Raman gain
      while suppressing stimulated Brillouin scattering (SBS) was utilized in a single
      stage counter-pumped Raman fiber amplifier. The SBS suppression was achieved
      through the acoustic tailoring of the core. A pump probe experiment was conducted
      to characterize the Brillouin gain and indicated the existence of multiple
      Brillouin peaks. When the amplifier was seeded with approximately 15 mW of 1178
      nm light, 11.5 W of cw output power was obtained with a linewidth <=2 MHz. The
      application of a thermal gradient to further mitigate the SBS process increased
      the output power to 18 W, thus providing a net amplifier gain >30 dB.

PMID- 22627565
TI  - Characterization of time-resolved laser differential phase using 3D complementary
      cumulative distribution functions.
AB  - An experimental method for characterizing the time-resolved phase noise of a fast
      switching tunable laser is discussed. The method experimentally determines a
      complementary cumulative distribution function of the laser's differential phase
      as a function of time after a switching event. A time resolved bit error rate of
      differential quadrature phase shift keying formatted data, calculated using the
      phase noise measurements, was fitted to an experimental time-resolved bit error
      rate measurement using a field programmable gate array, finding a good agreement
      between the time-resolved bit error rates.

PMID- 22627566
TI  - Nonreciprocal behavior and switching in optical couplers with longitudinally
      varying coupling coefficient.
AB  - We report the nonreciprocal behavior of an optical coupler consisting of two
      straight waveguides forming a small angle. An optical diode action is
      theoretically demonstrated when light is launched along opposite directions. The
      switching power is lower than the case of parallel waveguides with a constant
      coupling coefficient.

PMID- 22627567
TI  - Direct phase and amplitude characterization of femtosecond laser pulses
      undergoing filamentation in air.
AB  - Measurement of the temporal (spectral) phase and amplitude of a 50 fs laser pulse
      approaching and exceeding the critical power for self-focusing (P(crit)) in air
      reveals the formation of an isolated 17 fs pulse at 3P(crit). The dynamics of
      self-shortening are measured directly in the filament using transient-grating
      cross-correlation frequency-resolved optical gating with a noble gas serving as
      the nonlinear medium. Our results support recent filamentary propagation
      simulations, suggesting that a Kerr-dominated temporal reshaping process toward
      the end of the filament is largely responsible for the generation of short
      pulses.

PMID- 22627568
TI  - Octave-spanning super-continuum from a silica photonic crystal fiber pumped by a
      386 MHz Yb:fiber laser.
AB  - We report octave-spanning super-continuum generation in a silica photonic crystal
      fiber (PCF) pumped by a compact, efficient, mode-locked all-normal dispersion
      Yb:fiber laser. The laser achieved 45% optical-to-optical efficiency by using an
      optimized resonator design, producing chirped 750 fs pulses with a repetition
      rate of 386 MHz and an average power of 605 mW. The chirped pulses were
      compressed to 110 fs with a loss of only 4% by using multiple reflections on a
      pair of Gires-Tournois interferometer mirrors, yielding an average power of up to
      580 mW. The corresponding peak power was 13.7 kW and produced a super-continuum
      spectrum spanning from 696-1392 nm.

PMID- 22627569
TI  - Report on the p.Ser489X (p.Ser489*) CFTR mutation, a variant with severe
      associated phenotype and high prevalence in a Quebec French-Canadian cystic
      fibrosis patient population.
AB  - PURPOSE: This study reports on the phenotype of cystic fibrosis patients
      identified to be carriers of the p.Ser489X (p.Ser489*; c.1466C>A) cystic fibrosis
      transmembrane conductance regulator (CFTR) mutation, a variant rarely described
      in the cystic fibrosis literature, as well as on its allelic frequency in a
      French-Canadian cystic fibrosis patient cohort. METHODS: Reported phenotypes and
      allelic frequency of this variant were collected based on the data from a large
      French-Canadian cystic fibrosis patient cohort. RESULTS: Cystic fibrosis patients
      found to carry the p.Ser489X variant generally presented with classic
      gastrointestinal manifestations of this condition in infancy. The allelic
      frequency of this variant was calculated to be 0.7% for this population.
      CONCLUSION: The p.Ser489X CFTR variant is a severe disease-causing CFTR allele
      that is relatively frequent in the French-Canadian cystic fibrosis patient
      population, warranting its inclusion into CFTR molecular testing panel for this
      population.

PMID- 22627570
TI  - Usability testing of a Smartphone for accessing a web-based e-diary for self
      monitoring of pain and symptoms in sickle cell disease.
AB  - We examined the usability of smartphones for accessing a web-based e-Diary for
      self-monitoring symptoms in children and adolescents with sickle cell disease
      (SCD). One group of participants (n = 10; mean age, 13.1 +/- 2.4 y; 5 M; 5 F)
      responded to questions using precompleted paper-based measures. A second group (n
      = 21; mean age, 13.4 +/- 2.4 y; 10 M; 11 F) responded based on pain and symptoms
      they experienced over the previous 12 hours. The e-Diary was completed with at
      least 80% accuracy when compared to paper-based measures. Symptoms experienced
      over the previous 12 hours included feeling tired (33.3%), headache (28.6%),
      coughing (23.8%), lack of energy/fatigue (19.0%), yellowing of the eyes (19.0%),
      pallor (19.0%), irritability (19.0%), stiffness in joints (19.0%), general
      weakness (14.3%), and pain (14.3%), rating on average as 2.0 +/- 1.7 (on 0 to 10
      scale). Overall, sleep was good (8.1 +/- 1.4 on the 0 to 10 scale). In
      conclusion, children with SCD were able to use smartphones to access a web-based
      e-Diary for reporting pain and symptoms. Smartphones may improve self-reporting
      of symptoms and communication between patients and their health care providers,
      who may consequently be able to improve pain and symptom management in children
      and adolescents with SCD in a timely manner.

PMID- 22627571
TI  - Acute encephalopathy in the immune-compromised child: never forget toxoplasmosis.
AB  - Toxoplasma gondii is an opportunistic parasite, which very unusually may cause
      acute encephalitis in patients undergoing chemotherapy or hematopoietic stem cell
      transplant. The prognosis is usually dismal also because of late diagnosis,
      depending on the limited availability of specific diagnostic tools. An early
      diagnosis allows effective intervention with specific antibiotics, which may
      provide a chance for cure. We report 2 cases of cerebral toxoplasmosis in which
      the use of polymerase chain reaction on cerebrospinal fluid allowed a prompt
      diagnosis and specific therapy, which was followed by clinical response and
      negativization at follow-up studies of T. gondii genome on cerebrospinal fluid by
      polymerase chain reaction and by brain imaging.

PMID- 22627572
TI  - Spontaneous remission of childhood acute marrow fibrosis and megakaryoblastic
      leukemia.
AB  - Spontaneous remission in 2 children with myelofibrosis, one with megakaryocytic
      acute myeloblastic leukemia and t(1;22) (with recurrence later) and one with Down
      syndrome and GATA1 mutation (permanent), are described. One had sepsis and was
      treated with antibiotics and blood products, whereas the other received only
      blood products. Remission was spontaneous, without chemotherapy treatment.
      Possible explanations for these outcomes include immunologic response to sepsis
      by a leukemia-specific T-cell response or the release of various cytokines, such
      as tumor necrosis factor and interleukin-2, during infections. Natural killer and
      cytotoxic T cells transfused with blood products might have also triggered an
      immune response.

PMID- 22627573
TI  - Intraspinal mesenchymal chondrosarcoma in a 14-year-old patient: diagnostic and
      therapeutic problems in relation to the review of literature.
AB  - Mesenchymal chondrosarcoma (MC) is an infrequent, highly malignant neoplasm of
      the soft tissues and bone. It is very rare in the pediatric age group, especially
      in the intraspinal location. Only 24 cases have been reported to date. The
      authors present a case of a 14-year-old boy with an intraspinal MC who died of
      the disease 50 months from the initial diagnosis and after the third local
      recurrence. The patient was treated with a combination of chemotherapy,
      radiotherapy, and surgery. The authors review the clinical presentation,
      diagnostics, and the efficacy of treatment of pediatric patients with MC reported
      in the literature from 1978 to 2010.

PMID- 22627574
TI  - Scrub typhus-associated severe hemophagocytic lymphohistiocytosis with
      encephalomyelitis leading to permanent sequelae: a case report and review of the
      literature.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal
      disorder. There have been a few reports on HLH secondary to scrub typhus in
      adults. Here, we describe the case of a 9-year-old Korean girl who presented with
      the typical findings of HLH. Despite adequate antirickettsial and HLH treatment,
      the neurological impairment worsened and remained. This is the first case report
      of severe neurological impairment resulting from the very rare association of HLH
      with scrub typhus. Therefore, in endemic areas, a high index of suspicion for
      scrub typhus is warranted in patients presenting with HLH.

PMID- 22627575
TI  - Methemoglobin reductase deficiency:  novel mutation is associated with a disease
      phenotype of intermediate severity.
AB  - BACKGROUND: Cytochrome b5 reductase (CB5R) deficiency is a recessively inherited
      autosomal disorder that is either benign (type I) or associated with severe
      neurological problems (type II). Specific mutations in the CYB5R gene are not
      exclusive to each type. OBSERVATION: Two cyanotic children with developmental
      delay but with slow progression were investigated for CB5R deficiency. A novel
      mutation, p.Arg58Pro, was independently detected in both cases. CONCLUSIONS: The
      clinical variability and severity of the disease reflect the combined effects of
      impaired function of the 2 mutant enzymes. As illustrated by these 2 cases,
      inheritance of p.Arg58Pro with either p.Gly76Ser or pLeu188del causes a clinical
      condition more severe than type I and less severe than the type II cases reported
      to date.

PMID- 22627577
TI  - Polyclonal outbreak of vancomycin-resistant Enterococcus faecium in a pediatric
      oncology department.
AB  - We present a polyclonal outbreak of vancomycin-resistant enterococci (VRE)
      colonization in a pediatric oncology department and the role of a bundle of
      actions. After the occurrence of VRE bloodstream infections in 2 patients, an
      active surveillance of VRE colonization was started. Enhanced infection control
      measures and closure of the department to new admissions for the first 3 months
      were implemented. Among 32 patients screened for VRE, 21 were found colonized.
      Daily prevalence of VRE colonization among hospitalized patients ranged from 40%
      to 75%, but no new VRE infections occurred. Monthly incidence of VRE colonization
      decreased from 2.5 to 0.6 cases per 100 occupied bed-days at the end of this
      outbreak by the implementation of the above-mentioned measures. All VRE isolates
      tested were Enterococcus faecium carrying VanA gene. Pulsed field gel
      electrophoresis showed a polyclonal outbreak. A case-control study did not show
      any particular risk factors for colonization. High use of glycopeptide was noted
      before study outbreak that was drastically decreased during the study but only
      temporarily. Control of VRE in pediatric oncology departments with high
      colonization rates is challenging and requires a multifaceted strategy.
      Polyclonal spread of VRE found in this study suggests a possible effect of prior
      antimicrobial overuse and the critical need for antimicrobial stewardship
      especially in the era of multidrug-resistant bacteria.

PMID- 22627576
TI  - A case of severe toxicity during coadministration of vincristine and
      piperacillin:  are drug transporters involved in vincristine hypersensitivity and
      drug-drug interactions?
AB  - Neurotoxicity is frequent with vincristine treatment, but severe autonomic
      neuropathy is rare. A decreased activity of drug transporters in the presence of
      an interacting drug may favor such events by increasing systemic or tissue
      exposure to the drug. We encountered severe autonomic neuropathy and cholestasis
      in a child receiving vincristine, after the introduction of piperacillin
      tazobactam. A causality assessment of the adverse reaction identified the
      antibiotic as the most probable cause of the observation. The patient was
      heterozygous for several common polymorphisms of ABCC2 (multidrug-related protein
      2), CYP3A5, and ABCB1 (multidrug-related protein-1, P-glycoprotein), but their
      role in the toxicity cannot be ascertained.

PMID- 22627578
TI  - MYH9-related disorders: report on a patient of Greek origin presenting with
      macroscopic hematuria and presenile cataract, caused by an R1165C mutation.
AB  - Myosin heavy chain-9 (MYH9)-related disorders represent a heterogenous group of
      hereditary diseases caused by mutations in the gene encoding the heavy chain of
      nonmuscle myosin IIA. May-Hegglin anomaly and Fechtner, Sebastian, and Epstein
      syndromes are the four phenotypes of the disease, characterized by congenital
      macrothrombocytopenia and distinguished by different combinations of clinical
      signs that may include glomerulonephritis, sensorineural hearing loss, and
      presenile cataract. The spectrum of mutations responsible for the disease is wide
      and the existence of genotype-phenotype correlation remains a critical issue. We
      report the first case of an MYH9-RD in a patient of Greek origin presenting with
      macroscopic hematuria and presenile cataract caused by a p.R1165C mutation. The
      same mutation was present in the patient's father, who exhibited no
      extrahematological features of the disease. The p.R1165C mutation is one of the
      MYH9 alterations whose prognostic significance is still poorly defined. Thus, the
      patients described add to the limited existing data on the MYH9 mutations and
      their resultant phenotypes.

PMID- 22627579
TI  - Vancomycin-resistant Enterococcus in pediatric oncology patients: balancing
      infection prevention and family-centered care.
AB  - In February 2007, we experienced an abrupt 8-fold increase in vancomycin
      resistant Enterococcus (VRE)-positive pediatric hematology/oncology patients in
      isolation per day, peaking at 12 patients in isolation per day in June 2007. We
      enforced and expanded infection prevention practices and initiated a rigorous 6
      month clearance process. After noting an eventual decrease, we modified clearance
      to a 3-month process, maintaining <1 patient/day in isolation by June 2009,
      subjectively improving family and staff satisfaction after this 2-year process.
      VRE infection was relatively uncommon (7.8%), although continued VRE colonization
      portended an overall poorer prognosis.

PMID- 22627580
TI  - Langerhans cell histiocytosis:  40 years' experience.
AB  - OBJECTIVES: Our study analyzes 40 years' experience with pediatric Langerhans
      cell histiocytosis patients. MATERIALS AND METHODS: Between June 1968 and
      December 2009, 121 patients (79 males, 42 females; median age 4.13 y) were
      diagnosed at our center (74% monosystemic disease; 26% multisystemic), treated
      according to current protocols. We evaluated the response, the survival, and the
      neuroendocrinological sequelae. RESULTS: Overall survival (OS) for all patients
      was 93% at 10 years from diagnosis, event-free survival (EFS) 77%. OS for
      patients younger than 2 years and older than or equal to 2 years was 82% and 97%
      (P = 0.003); EFS 48% and 87% (P = 0.001). OS for patients diagnosed before and
      after April 1, 1991 was 84% and 98% (P = 0.007), EFS 66% and 85% (P = 0.03). OS
      for monosystemic and multisystemic disease was 100% and 71% (P < 0.001); EFS 88%
      and 45% (P < 0.001). OS for "risk" patients (involvement of bone marrow, spleen,
      liver, lungs) and "low-risk" patients was 50% and 94% (P = 0.007), EFS 37% and
      54% (P = 0.06). Fourteen patients developed diabetes insipidus, 7 patients growth
      hormone deficiency, 2 hypothyroidism, and 1 neurodegeneration. CONCLUSIONS: Our
      study confirms improvement of pathogenetic knowledge and treatment over the last
      20 years. Age at diagnosis older than or equal to 2 years and standardized
      treatment are associated with improved prognoses. Multisystemic involvement,
      especially with "risk" organs seem to be correlated to a worse outcome.

PMID- 22627581
TI  - Electrode migration in cochlear implant patients: not an exception.
AB  - OBJECTIVE: It was the aim of this study to investigate the occurrence of
      electrode migration of a cochlear implant in patients with and without
      complaints. METHODS: We performed a retrospective case review in a tertiary
      referral center. The electrode position was evaluated in 35 cochlear implantees,
      16 with a CII HiFocus1 (non-positioner) and 19 with a HiRes90K HiFocus1J, using
      multiplanar reconstructions of the postoperative CT scans. Of 5 patients, a
      second scan was obtained to evaluate complaints of performance drop, vertigo,
      tinnitus, headache or nonauditory stimulation. Displacements of the electrode
      contacts were calculated and displacements of >1 mm were considered a migration.
      The possible correlation with implant type, insertion depth or presence of
      complaints was analyzed. RESULTS: Migrations were detected in 10 patients (29%).
      There was a significant effect of the implant type in favour of the HiFocus1, but
      no relation with the original insertion depth of the device. In the 5 patients
      scanned because of complaints, two migrations were detected. CONCLUSIONS: In our
      patient population, electrode migration was not uncommon and turned out to occur
      in patients with and without complaints.

PMID- 22627582
TI  - Alterations of sympathetic nervous system, coagulation and platelet function in
      gestational diabetes.
AB  - Gestational diabetes is associated with increased risk for venous
      thromboembolism. Activation of sympathetic nervous system affects blood
      coagulation, fibrinolysis and platelet activation by several mechanisms. We aimed
      to study the relationship of sympathetic nervous system, coagulation and platelet
      function in gestational diabetes. Forty-one white women with gestational
      diabetes, 22 healthy pregnant and 14 nonpregnant controls were studied. We
      assayed serial nocturnal (at 12 p.m., 4 a.m. and 7 a.m.) changes of the
      adrenergic transmitter noradrenaline, coagulation variables and platelet
      activation with PFA-100. Plasma noradrenaline increased from 4 to 7 a.m. in both
      pregnant groups. During the same time period, prothrombin time (PT) shortened in
      gestational diabetes compared with healthy pregnant and nonpregnant controls. In
      gestational diabetes, nocturnal FVIII:C levels were lower compared with normal
      pregnancy and also variables associated with von Willebrand factor tended to be
      lower. Platelet activity increased at midnight in pregnant women compared with
      nonpregnant women without differences between gestational diabetes and normal
      pregnancy. Gestational diabetes is associated with concomitant early morning
      sympathetic stimulation and activation of extrinsic coagulation pathway
      (shortened PT). Decreased FVIII:C may refer to compensatory anticoagulatory
      mechanism. These alterations could reflect increased risk of pregnancy-related
      thromboembolism in gestational diabetes.

PMID- 22627583
TI  - Association of platelet collagen receptor polymorphisms with premature acute
      myocardial infarction.
AB  - The impact of platelet collagen receptor polymorphisms in the pathogenesis of
      myocardial infarction at young age remains unknown. To determine whether either
      of the two platelet collagen receptor polymorphisms (GP VI T13254C and GP Ia
      C807T) was associated with premature acute myocardial infarction. One hundred
      patients with premature acute myocardial infarction and 100 age-matched controls
      with normal coronary angiograms were studied. Genotyping was done using PCR
      followed by restriction fragment length polymorphism (RFLP). GP Ia C807T
      polymorphism was more frequent in the patient group (65%) than in the control
      group (53%). However, there was no association between this polymorphism and
      premature acute myocardial infarction (P = 0.08). The prevalence of T13254C
      polymorphism did not differ between patients (38%) and controls (33%), and this
      polymorphism was not associated with premature acute myocardial infarction (P =
      0.46). Logistic regression analysis also indicated no association between these
      polymorphisms and premature acute myocardial infarction (C807T with P = 0.51 and
      T13254C with P = 0.20). There is no association between GP VI T13254C or GP Ia
      C807T polymorphisms and premature acute myocardial infarction.

PMID- 22627584
TI  - Does risk-based coagulation screening predict intraventricular haemorrhage in
      extreme premature infants?
AB  - BACKGROUND: Intraventricular haemorrhage (IVH) continues to be a significant
      contributor to neonatal morbidity and mortality, especially in the extremely
      premature population (<26 weeks). The aims of the study were to test the
      hypothesis that risk-based coagulopathy screening could identify infants at risk
      of severe IVH/mortality, and whether preterm infants born at less than 26 weeks
      of gestation who received early (within first 48 h) fresh frozen plasma (FFP) had
      a lower incidence of IVH than those who did not. METHOD: Chart review of preterm
      infants born less than 26-week gestation was conducted. The study compared two
      cohorts of infants who either had 'early' risk-based coagulopathy screening
      (within first 48 h, n = 47) or 'late' screening (n = 55). RESULTS: Baseline and
      clinical characteristics of the two cohorts were similar. 'Early' coagulopathy
      screening predicted infants at risk of severe IVH [relative risk (RR) 2.59, 95%
      confidence interval (CI) 1.18-5.67, P < 0.01] but not mortality (RR 1.2, 95% CI
      0.79-1.94). FFP was administered significantly more in the 'early' screened
      cohort (P < 0.001); however, the incidence of IVH was similar in those who
      received early FFP administration than those who did not. CONCLUSIONS: 'Early'
      risk-based coagulopathy screening may identify preterm infants at risk of severe
      IVH; however, the study failed to show any benefit of early treatment of a
      coagulopathy with FFP in a small but high-risk population.

PMID- 22627590
TI  - Inverse relation between cortisol and anger and their relation to performance and
      explicit memory.
AB  - Cortisol has been found to increase in response to social evaluative threat.
      However, little is known about the cortisol response to induced anger. Thus, in
      the present study, we investigated the cortisol response to anger induction and
      its effects on performance and explicit memory. A variant of the Montreal Stress
      Imaging Task (MIST; Dedovic et al., 2005) was used to induce anger in 17 male and
      17 female students. Consistent with previous observations, a significant decrease
      in cortisol was found from pre to post manipulation which was inversely related
      to increases in subjective anger. Moreover, whereas anger increase was related to
      impairments in performance, cortisol reduction was inversely related to cognitive
      performance and explicit memory (recall and recognition of persons' features in a
      social memory task). The adaptive value of an increase in cortisol in response to
      fear or uncontrollability and of a decrease in cortisol in response to anger will
      be discussed.

PMID- 22627591
TI  - Deficiencies of antithrombin, protein C and protein S - practical experience in
      genetic analysis of a large patient cohort.
AB  - Deficiencies of natural anticoagulant proteins including antithrombin (AT),
      protein C (PC) and protein S (PS) are important causes of inherited
      thrombophilia. This study aimed to report on the practical experience gained in
      performing genetic analyses of a large cohort of patients with AT, PC and PS
      deficiencies and to relate this knowledge to clinical application. We genotyped a
      large cohort of 709 unrelated patients with AT (231), PC (234) and PS (244)
      deficiencies referred to us by physicians throughout Germany. Mutations were
      detected by direct sequencing and multiplex ligation-dependent probe
      amplification (MLPA). The highest mutation detection rate (MDR) was found for the
      SERPINC1  gene (83.5%), followed by the  PROC  (69%) and  PROS1  (43%) genes.
      Even at AT activities close to the normal range (75%), the MDR was 70%.
      Contrastingly, for PC and PS deficiencies, the MDR dropped significantly and
      mildly lowered to subnormal values. At PS activities >55% for PS no mutations
      were detected. Mutation profiles of all three genes were similar with the highest
      prevalence for missense mutations (63-78%), followed by nonsense (7-11%), splice
      site mutations (7-13%), small deletions (1-8%), small insertions/duplications (1
      4%) and large deletions (3-6%). In conclusion, genetic testing is a useful
      diagnostic tool for diagnosing thrombophilia. Based on our data, genetic analysis
      for patients with AT deficiency is indicated for all subnormal activities. In
      contrast, genotyping is not advisable for PC activities >70% and for PS
      activities >55%.

PMID- 22627592
TI  - The shady side of dasatinib.

PMID- 22627593
TI  - Antibiotics as first-line therapy for Hp-associated gastric large B-cell
      lymphoma? Probably yes.

PMID- 22627594
TI  - Decoding HSC heterogeneity.

PMID- 22627595
TI  - Rare cells predict GVHD.

PMID- 22627597
TI  - Low contrast agent and radiation dose protocol for hepatic dynamic CT of thin
      adults at 256-detector row CT: effect of low tube voltage and hybrid iterative
      reconstruction algorithm on image quality.
AB  - PURPOSE: To evaluate the effect on image quality of a low contrast agent dose and
      radiation dose protocol at abdominal dynamic computed tomography (CT) with a low
      tube voltage, hybrid iterative reconstruction algorithm, and a 256- detector row
      scanner. MATERIALS AND METHODS: This prospective study received institutional
      review board approval, and prior informed written consent was obtained from all
      patients. Seventy-four patients undergoing hepatic dynamic CT were randomly
      assigned to one of two protocols: Thirty-nine patients underwent scanning with
      the conventional 120-kVp protocol and the other 35 patients underwent scanning
      with an 80-kVp tube voltage and a 40% reduction in contrast agent dose. The 80
      kVp images were also postprocessed with a hybrid iterative reconstruction
      algorithm. The estimated effective radiation dose of each protocol was compared
      and the image noise and contrast-to-noise-ratio (CNR) of the 120-kVp, 80-kVp, and
      hybrid iterative reconstructed 80-kVp images were evaluated by using the Student
      t test. RESULTS: The effective radiation dose was 51% lower during the hepatic
      arterial phase (HAP) and 48% lower during the portal venous phase (PVP) with the
      80-kVp protocol than with the 120-kVp protocol (HAP: 5.6 mSv +/- 1.0 [standard
      deviation] vs 11.6 mSv +/- 3.3; PVP: 5.8 mSv +/- 0.7 vs 11.2 mSv +/- 3.2,
      respectively). The hybrid iterative reconstruction decreased image noise by 23%
      during the HAP (9.2 +/- 1.9 vs 12.0 +/- 2.6) and by 24% during the PVP (9.4 +/-
      1.8 vs 12.3 +/- 2.6). There were no significant differences in the CNR of any of
      the regions of interest between 80-kVp with iterative reconstruction and 120-kVp
      protocols (P = .46-.85). CONCLUSION: A low tube voltage and the hybrid iterative
      reconstruction algorithm can dramatically decrease radiation and contrast agent
      doses with adequate image quality at hepatic dynamic CT of thin adults with use
      of a 256-detector row scanner.

PMID- 22627598
TI  - Nontraumatic subarachnoid hemorrhage management: evaluation with reduced iodine
      volume at CT angiography.
AB  - PURPOSE: To evaluate the technical quality and the diagnostic performance of a
      protocol with use of low volumes of contrast medium (25 mL) at 64-detector spiral
      computed tomography (CT) in the diagnosis and management of adult, nontraumatic
      subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: This study was performed
      outside the United States and was approved by the institutional review board.
      Intracranial CT angiography was performed in 73 consecutive patients with
      nontraumatic SAH diagnosed at nonenhanced CT. Image quality was evaluated by two
      observers using two criteria: degree of arterial enhancement and venous
      contamination. The two independent readers evaluated diagnostic performance
      (lesion detection and correct therapeutic decision-making process) by using
      rotational angiographic findings as the standard of reference. Sensitivity,
      specificity, and positive and negative predictive values were calculated for
      patients who underwent CT angiography and three-dimensional rotational
      angiography. The intraclass correlation coefficient was calculated to assess
      interobserver concordance concerning aneurysm measurements and therapeutic
      management. RESULTS: All aneurysms were detected, either ruptured or unruptured.
      Arterial opacification was excellent in 62 cases (85%), and venous contamination
      was absent or minor in 61 cases (84%). In 95% of cases, CT angiographic findings
      allowed optimal therapeutic management. The intraclass correlation coefficient
      ranged between 0.93 and 0.95, indicating excellent interobserver agreement.
      CONCLUSION: With only 25 mL of iodinated contrast medium focused on the arterial
      phase, 64-detector CT angiography allowed satisfactory diagnostic and therapeutic
      management of nontraumatic SAH.

PMID- 22627599
TI  - Exposing exposure: enhancing patient safety through automated data mining of
      nuclear medicine reports for quality assurance and organ dose monitoring.
AB  - PURPOSE: To develop and validate an open-source informatics toolkit capable of
      creating a radiation exposure data repository from existing nuclear medicine
      report archives and to demonstrate potential applications of such data for
      quality assurance and longitudinal patient-specific radiation dose monitoring.
      MATERIALS AND METHODS: This study was institutional review board approved and
      HIPAA compliant. Informed consent was waived. An open-source toolkit designed to
      automate the extraction of data on radiopharmaceuticals and administered
      activities from nuclear medicine reports was developed. After iterative code
      training, manual validation was performed on 2359 nuclear medicine reports
      randomly selected from September 17, 1985, to February 28, 2011. Recall
      (sensitivity) and precision (positive predictive value) were calculated with 95%
      binomial confidence intervals. From the resultant institutional data repository,
      examples of usage in quality assurance efforts and patient-specific longitudinal
      radiation dose monitoring obtained by calculating organ doses from the
      administered activity and radiopharmaceutical of each examination were provided.
      RESULTS: Validation statistics yielded a combined recall of 97.6% +/- 0.7 (95%
      confidence interval) and precision of 98.7% +/- 0.5. Histograms of administered
      activity for fluorine 18 fluorodeoxyglucose and iodine 131 sodium iodide were
      generated. An organ dose heatmap which displays a sample patient's dose
      accumulation from multiple nuclear medicine examinations was created. CONCLUSION:
      Large-scale repositories of radiation exposure data can be extracted from
      institutional nuclear medicine report archives with high recall and precision.
      Such repositories enable new approaches in radiation exposure patient safety
      initiatives and patient-specific radiation dose monitoring.

PMID- 22627600
TI  - "Tumoral pseudoblush" identified within gliomas at high-spatial-resolution
      ultrahigh-field-strength gradient-echo MR imaging corresponds to microvascularity
      at stereotactic biopsy.
AB  - PURPOSE: To use directed biopsy sampling to determine whether microvascular
      assessment within gliomas, by means of ultrahigh-field-strength high-spatial
      resolution gradient-echo (GRE) magnetic resonance (MR) imaging at 8 T, correlates
      with histopathologic assessment of microvascularity. MATERIALS AND METHODS: The
      study was institutional review board approved and HIPAA compliant. Informed
      consent was obtained. Thirty-five subjects with gliomas underwent 8-T and 80-cm
      MR imaging by using a GRE sequence (repetition time, 600-750 msec; echo time, 10
      msec; in-plane resolution, 196 mm). Haphazardly arranged serpentine low-signal
      intensity structures, often associated with areas of low signal intensity within
      the tumor bed ("tumoral pseudoblush") at MR imaging, were presumed to be related
      to tumoral microvascularity. Microvessel density (MVD) and microvessel size (MVS)
      ranked with a semiquantitative three-tier scale (high, medium, and low) relative
      to cortical penetrating veins were assessed from regions of interest identified
      at MR imaging and were compared with a similar assessment of stereotactic biopsy
      specimens by using Kendall taub. Tumor grade (high vs low) was compared with
      ultrahigh-field-strength high-resolution GRE MR analysis by using Pearson chi2.
      Discrepancies between 8-T and histopathologic assessment were identified and
      analyzed. RESULTS: Ultrahigh-field-strength high-resolution GRE MR imaging and
      histopathologic assessment concurred for MVS (P<.0001) and MVD (P<.0001). World
      Health Organization classification tumor grade was associated with number
      (P<.0005) and size (P<.0005) of foci of microvascularity within the tumor bed at
      8-T MR imaging. Radiation-induced microvessel hyalinosis mimicked tumor
      microvascularity at 8-T MR imaging. Potential confounders could result from
      radiofrequency inhomogeneity and displaced normal microvasculature. CONCLUSION:
      Microvascularity identified as a tumoral pseudoblush at ultrahigh-field-strength
      high-resolution GRE MR imaging without contrast material shows promise as a
      marker for increased tumoral microvascularity.

PMID- 22627601
TI  - Intrahepatic cholangiocarcinoma treated with local-regional therapy: quantitative
      volumetric apparent diffusion coefficient maps for assessment of tumor response.
AB  - PURPOSE: To evaluate volumetric changes in apparent diffusion coefficient (ADC)
      and contrast material enhancement on contrast-enhanced (CE) magnetic resonance
      (MR) images in hepatic arterial and portal venous phases for assessing early
      response in cholangiocarcinoma treated with transcatheter arterial
      chemoembolization (TACE). MATERIALS AND METHODS: Twenty-nine patients with
      unresectable cholangiocarcinoma, including 11 men (mean age, 60 years; standard
      deviation, 16.8) and 18 women (mean age, 63 years; standard deviation, 11.5) were
      included in this retrospective institutional review board-approved, HIPAA
      compliant study; informed consent was waived. Sixty-nine TACE procedures were
      performed during the observational time (range, one to five TACE sessions). No
      patients received another form of therapy after treatment with TACE. MR Imaging
      was performed before and 3-4 weeks after TACE, and images were analyzed with a
      semiautomatic volumetric software package. Patients were stratified as responders
      and nonresponders on the basis of overall survival (OS) as the primary end point.
      Differences between responders and nonresponders were analyzed with paired t
      tests, and OS was calculated with the Kaplan-Meier method. Significant
      differences were analyzed with the log-rank test. RESULTS: Mean volumetric ADC
      increased from 1.54*10(-3) mm2/sec to 1.92*10(-3) mm2/sec (P<.0001), with no
      significant decrease in mean volumetric enhancement in hepatic arterial (40.6% vs
      37.5%, P=.546) and portal venous (79.0% vs 70.0%, P=.105) phases. Patients who
      demonstrated improved survival of 10 months or more had a significant increase in
      mean volumetric ADC and volumetric ADC above the threshold level of 1.60*10(-3)
      mm2/sec (P<.002). Patients with 45% or greater (n=21; log-rank test, P<.02) and
      60% or greater (n=12; log-rank test, P<.009) ADC changes for the whole tumor
      volume demonstrated better OS compared with patients in whom these ADC changes
      were not achieved. CONCLUSION: Patients with percentage tumor volume increase in
      ADC of 45% or greater and 60% or greater above the threshold level of 1.60*10(-3)
      mm2/sec had favorable response to therapy and improved survival.

PMID- 22627602
TI  - Islet cell liver metastases: assessment of volumetric early response with
      functional MR imaging after transarterial chemoembolization.
AB  - PURPOSE: To assess early response to transarterial chemoembolization by using
      volumetric functional magnetic resonance (MR) imaging in patients with islet cell
      liver metastases (ICLMs). MATERIALS AND METHODS: This retrospective institutional
      review board-approved HIPAA-compliant study included 215 ICLMs in 26 patients (15
      men, 11 women; mean age, 59.7 years; age range, 37-79 years). Volumetric
      measurements were performed by an experienced radiologist on diffusion-weighted
      and contrast material-enhanced MR images at baseline and 1-month follow-up.
      Measurements included mean change (three-dimensional [3D] mean apparent diffusion
      coefficient [ADC], 3D mean enhancement) and percentage of tumor with change above
      a predetermined threshold (3D threshold ADC, 3D threshold enhancement). Response
      by volumetric measurements at 1-month follow-up was compared with Response
      Evaluation Criteria in Solid Tumors (RECIST) at 6-month follow-up. Lesions that
      had complete or partial response were considered responders, while those with
      stable or progressive disease were considered nonresponders. Statistical analysis
      included the t test, receiver operating characteristic (ROC) curve analysis, and
      logistic regression analysis. RESULTS: RECIST criteria at 6-month follow-up
      indicated 78 (36.3%) lesions responded, while 137 (63.7%) did not. The increase
      in 3D mean ADC was significantly higher in responders than in nonresponders
      (median, 26.2% vs 10.9%; P<.001). The 3D threshold ADC was 71.1% in responders
      and 47.6% in nonresponders (P<.001). Decrease in 3D mean arterial enhancement
      (AE) was significantly higher in responders than in nonresponders (median, 40.5%
      vs 18.0%; P<.001). Decrease in 3D mean venous enhancement (VE) was significantly
      higher in responders than in nonresponders (median, 28.0% vs 10.0%; P<.001). The
      3D threshold VE and 3D threshold AE did not differ between responders and
      nonresponders. In unadjusted logistic regression analyses, 3D mean ADC and 3D
      threshold ADC had the highest odds ratio (1.02 and 1.03, respectively) and the
      largest area under the ROC curve (0.698 and 0.695, respectively). CONCLUSION:
      Volumetric functional MR imaging could be used to predict early response of
      hepatic ICLMs to therapy and to distinguish between responders and nonresponders.

PMID- 22627603
TI  - Effect of an angiogenesis inhibitor on hepatic tumor perfusion and the
      implications for adjuvant cytotoxic therapy.
AB  - PURPOSE: To determine whether dynamic contrast material-enhanced (DCE) computed
      tomography (CT) can help identify hepatic tumor perfusion response to vascular
      remodeling induced by antiangiogenesis treatment in a rabbit model. MATERIALS AND
      METHODS: The study was approved by the Animal Use Subcommittee of the University
      Council on Animal Care. DCE CT hepatic perfusion measurements were performed in
      the livers of 20 rabbits implanted with VX2 carcinoma. Vascular remodeling was
      induced with thalidomide dissolved in dimethyl sulfoxide and sterile water,
      starting at a tumor diameter of 0.7 cm+/-0.1 and continuing until metastatic lung
      nodules were observed. The control group (n=8) was given an equivalent volume of
      the vehicle. The therapy group was subdivided into animals that survived for more
      than 24 days without lung metastasis (responder group, n=5) or those that
      survived for less than 24 days (nonresponder group, n=7). Data were analyzed with
      the Kruskal-Wallis or Friedman rank test and reported as medians and
      interquartile ranges. RESULTS: DCE CT depicted differential perfusion change
      within the therapy group after treatment. By day 4, hepatic blood volume (HBV) in
      the responder group decreased by 29.2% (-32.5% to -11.8%) relative to that before
      treatment and was significantly different from that in the nonresponder (P=.048)
      and control (P=.011) groups, where HBV remained stable. By day 8, hepatic artery
      blood flow decreased by 50.0% (-59.08% to -21.05%) relative to that before
      treatment in the responder group and was significantly different from that in the
      nonresponder and control groups (P=.030 for both), which remained stable at -3.5%
      (-8.5% to 28.7%, P=.50) and -10.0% (-33.8% to 10.4%, P=.48), respectively.
      CONCLUSION: DCE CT can help differentiate responders from nonresponders by their
      early differential perfusion response to antiangiogenesis therapy.

PMID- 22627604
TI  - Postantibiotic effect of various antibiotics on Legionella pneumophila strains
      isolated from water systems.
AB  - The postantibiotic effects (PAE) of azithromycin, clarithromycin, ciprofloxacin,
      and levofloxacin were investigated against Legionella pneumophila (L.
      pneumophila) strains isolated from several hot water systems of different
      buildings in Istanbul. Each strain in logarithmic phase of growth was exposed to
      concentrations of antibiotics equal to minimum inhibitory concentration (MIC) and
      4* MIC for 1 h. Recovery periods of test cultures were evaluated after
      centrifugation using the viable counting method. The mean values of PAEs for the
      strains of L. pneumophila, azithromycin at a concentration equal to and 4 times
      of MIC values were found 1.75 +/- 0.28 h and 4.06 +/- 0.44 h, for clarithromycin
      2.98 +/- 0.70 h and 4.18 +/- 0.95 h, for ciprofloxacin 2.97 +/- 0.63 h and 4.70
      +/- 0.63 h, for levofloxacin 2.05 +/- 0.33 h and 3.78 +/- 0.46 h, respectively.
      All of the antibiotics showed increased PAE values in a concentration-dependent
      manner. The findings of our study may play useful role in selecting the
      appropriate timing of doses during therapy with antimicrobials to treat patients
      infected with L. pneumophila.

PMID- 22627605
TI  - Update on HIV-1 diversity in Africa: a decade in review.
AB  - BACKGROUND: HIV-1 strains have diversified extensively through mutation and
      recombination since their initial transmission to human beings many decades ago
      in Central Africa in the first part of the 20th Century (between 1915 and 1941).
      The upward trend in global HIV-1 diversity has continued unabated, with newer
      groups, subtypes, and unique and circulating recombinants increasingly being
      reported, especially in Africa. OBJECTIVE: In this review, we focus on the
      extensive diversity of HIV-1 over a decade (2000-2011), in 51 countries of the
      three African geographic regions (eastern and southern, western and central, and
      northern Africa) as per the WHO/UNAIDS 2010 classification. METHODOLOGY:
      References for this review were identified through searches of PubMed, conference
      abstracts, Google Scholar, and Springer Online Archives Collection. We retrieved
      273 citations, of which 200 reported HIV-1 diversity from Africa from January,
      2000 to August, 2011. Articles resulting from these searches and relevant
      references cited in those articles were reviewed. Articles published in English
      and French were included. FINDINGS: There has been a high diversity of HIV-1 in
      its epicenter, west-central Africa. A few subtypes, namely, A (A1, A2, A3, A4,
      A5), C, CRF02_AG, and D accounted for about 85% of new infections. Subtype A and
      D have been stable in East Africa; C in southern Africa; A, G, CRF02_AG, and
      CRF06_cpx in western Africa; and subtype B and CRF02_AG in northern Africa.
      Recently a new putative group, designated P, was reported to be found in two
      Cameroonians. CONCLUSION: The regional distributions of individual subtypes and
      recombinants are broadly stable, although unique/circulating recombinant forms
      may play an increasing role in the HIV pandemic. Understanding the kinetics and
      directions of this continuing adaptation and its impact on viral fitness,
      immunogenicity, and pathogenicity are crucial to the successful design of
      effective HIV vaccines. There is need for regular monitoring and review updates,
      such as the one presented here, to assist countries to plan and anticipate
      complex forms that may be introduced with time.

PMID- 22627606
TI  - Psychopharmacological treatments in HIV patients under antiretroviral therapy.
AB  - Human immunodeficiency virus-infected patients have high rates of psychiatric
      disorders, including substance and alcohol abuse. Prompt identification and
      effective management of mental disorders can improve the quality of life and
      antiretroviral adherence in HIV patients. Additive side effects and drug
      interactions may complicate the psychopharmacological treatment in this
      population. This article reviews the indications and precautions needed when
      prescribing psychoactive drugs to HIV patients with mental disorders.

PMID- 22627607
TI  - Fat redistribution syndromes associated with HIV-1 infection and combination
      antiretroviral therapy.
AB  - More than 15 years after the introduction of highly active antiretroviral
      therapy, HIV/HAART-associated lipodystrophy syndrome still shadows the
      indisputable efficacy of antiretroviral therapy. Several issues related to this
      complication (prevalence, diagnosis, pathogenesis, prevention, or clinical
      management) have not been completely clarified. However, in the last years,
      substantial progress has been made in elucidating some of these basic aspects.
      This includes a better knowledge of the pathogenic mechanisms underlying
      HIV/HAART-associated lipodystrophy syndrome such as genetic host determinants,
      the impact of HIV infection per se, as well as the contribution of antiretroviral
      therapy. In regard to treatment, we have learned that certain drugs are
      especially prone to cause HIV/HAART-associated lipodystrophy syndrome (i.e.
      thymidine analogues). Pharmacological interventions to treat this condition have
      yielded mostly disappointing results, and the only intervention which offers an
      immediate aesthetical improvement for patients with HIV/HAART-associated
      lipodystrophy syndrome is plastic surgery. Even under the most favorable
      conditions (ideal host genetic make-up, and the timely initiation of HIV therapy
      with less toxic drugs), current data show that HIV/HAART-associated lipodystrophy
      syndrome is a complication of HIV infection and/or antiretroviral treatment that
      we are unable to avoid. In the context of HIV-1-infected patients under long-term
      antiretroviral therapy, fat toxicity is still the dark side of the rainbow.

PMID- 22627608
TI  - Impact of hepatitis C co-infection on response to antiretroviral treatment.
AB  - The MONET study, comparing darunavir/ritonavir-based triple therapy and
      monotherapy, has found higher risk of failure in patients with positive HCV
      serology, but the effects of HCV co-infection on the efficacy of antiretroviral
      treatment have not been clearly established. A detailed MEDLINE search was
      conducted to identify cohort studies and clinical trials with published analyses
      of the efficacy of antiretroviral treatment by HCV co-infection. A meta-analysis
      of the clinical trials was conducted, with the standardized endpoint of HIV RNA <
      50 copies/ml at week 48 (intent to treat, time to loss of virologic response
      algorithm). Twelve cohort studies, seven clinical trials in antiretroviral-naive
      patients and three in pretreated patients were identified. In the clinical
      trials, 637/5,408 (12%) patients had HIV/HCV co-infection by HCV antibody tests;
      this percentage was in the lower range of the percentage of HIV/HCV co-infected
      patients reported in cohort studies in North America and Europe (median 37%,
      range 9-64%). In the meta-analysis of the clinical trials, the mean percentage of
      patients achieving HIV RNA < 50 copies/ml at week 48 was 68.2% for HIV/HCV co
      infected patients versus 80.4% for HIV mono-infected patients. The absolute
      difference in efficacy was 11.5% (95% CI: 7.7-15.3%; p < 0.001). However, a high
      proportion of endpoints in the time to loss of virologic response analysis were
      discontinuations of randomized treatment for adverse events or other reasons. The
      cause of the lower efficacy of antiretroviral treatment in HIV/HCV co-infected
      patients is unclear. The low percentage of HIV/HCV co-infected patients in this
      analysis, compared with published cohort studies, suggests that HCV co-infected
      patients are underrepresented in HIV clinical trials.

PMID- 22627609
TI  - Contemporary role of nevirapine in HIV treatment.
AB  - Nevirapine was the first nonnucleoside reverse transcriptase inhibitor that was
      approved for treatment of HIV infection and quickly became an important component
      of HAART. As experience with this drug grew, potential toxicities and significant
      clinical benefits became apparent. With the development of new patient criteria
      based on CD4(+) cell counts, new treatment initiation guidelines were developed.
      Incorporation of these criteria has reduced the incidence of rare but significant
      toxicities associated with nevirapine therapy to levels seen with other drugs.
      For treatment-naive patients who meet established starting criteria, or for
      patients switching from other nonnucleoside reverse transcriptase inhibitor- or
      protease inhibitor-based regimens, nevirapine can offer potent and durable viral
      suppression with significant clinical benefits. These benefits include the
      absence of central nervous system effects in patients who are at risk for
      depression, minimal untoward effects on serum lipid profiles, which is especially
      important for patients who have other cardiovascular disease risk factors, and
      relative safety during pregnancy for women of childbearing age. Patients who
      should avoid nevirapine include those with prior hypersensitivity reactions,
      those who do not meet treatment initiation criteria, those who experience adverse
      reactions during induction, and those with existing hepatotoxicity. This review
      focuses on current information regarding the role of nevirapine in HAART and
      defines patient groups whose clinical profiles may warrant consideration of
      nevirapine.

PMID- 22627610
TI  - Computational models for prediction of response to antiretroviral therapies.
AB  - This review describes the state-of-the-art in statistical, machine learning, and
      expert-advised computational methods for the evaluation and optimization of
      combination antiretroviral therapy, with respect to the virologic outcomes in HIV
      1-infected patients. Currently employed methodologies are based on the paradigm
      for which mutations present in patient viral genotypes, selected either by
      treatment or already transmitted to the patient as resistant mutants, are the
      major drivers of virologic outcomes. Genotypic interpretation systems have been
      designed with the prime objective of characterizing the resistance to individual
      drugs, deriving scores from the association of viral genotypes with in vitro
      phenotypic drug susceptibility or in vivo response to treatment. Nevertheless,
      the very large range of possible drug combinations and of viral mutational
      patterns leads to an extremely complex scenario, making prediction of in vivo
      treatment response extremely challenging. To deal with such complexity, machine
      learning methods are being increasingly explored, thanks to the availability of
      exponentially growing HIV data bases in recent years. The combination of
      genotypic interpretation systems with other laboratory markers, treatment
      history, past clinical events, and the usage of data-driven techniques has
      dramatically raised the confidence in predicting virologic outcomes. A few of
      these systems have been implemented as free web-services, indicating ranks of
      suitable combination antiretroviral therapy regimens given a patient's clinical
      background. Future perspectives in the field foresee the extension of therapy
      optimization systems to newly approved antiretroviral drug targets and the
      prediction of other clinical outcomes, rather than the sole virologic response.

PMID- 22627611
TI  - Cancer cell death and selection: unexpected putative roles for pRb2/p130, BORIS
      and CTCF in endoplasmic stress response maintained by the T-antigen.

PMID- 22627612
TI  - Long-term follow-ups of revascularized immature necrotic teeth: three case
      reports.
AB  - Revascularization of immature necrotic teeth is a reliable treatment alternative
      to conventional apexogenesis or apexification. In case 1, a 12-year-old boy had
      his necrotic, immature mandibular left second premolar treated with a
      revascularization technique. At a24-month follow-up, periapical radiolucency had
      disappeared and thickening of the root wall was observed. In cases 2 and 3, a10
      year-old boy had his necrotic, immature, bilateral mandibular second premolars
      treated with the same modality. At 48-month(in case 2) and 42-month (in case 3)
      follow-ups, loss of periapical radiolucencies and increases in the root wall
      thickness were also observed.

PMID- 22627613
TI  - Papillae alterations around single-implant restorations in the anterior maxillae:
      thick versus thin mucosa.
AB  - To evaluate the papilla alterations around single-implant restorations in the
      anterior maxillae after crown attachment and to study the influence of soft
      tissue thickness on the papilla fill alteration. According to the inclusion
      criteria, 32 patients subjected to implant-supported single-tooth restorations in
      anterior maxillae were included. The patients were assigned to two groups
      according to the mucosal thickness: (i) group 1, 1.5 mm s mucosal thickness 3 mm;
      and (ii) group 2, 3 mm<mucosal thickness 4.5 mm.Assessments of interproximal
      papillae at the time of crown placement (baseline) and at 6-month post loading
      (follow-up) were made by two prosthodontists using papilla fill index (PFI). The
      mean mucosal thickness was (2.49+/-_0.31) mm (group 1) and (3.81+/-_0.31)
      mm(group 2) for the two groups respectively. A significant difference in PFI
      between the groups was detected at the baseline (P<0.001).PFI improvements over
      time occurred after 6-month follow-up irrespective of the groups. When compared
      to group 1, the likelihood to obtain papilla fill was significantly higher for
      group 2 with an odds ratio of 6.05 (P<0.001). The interproximal papilla level
      around single-implant restorations could improve significantly over time after 6
      month restoration according to PFI assessment. The thicker mucosa before implant
      placement implied a more favorable esthetic outcome in papilla alteration.

PMID- 22627614
TI  - Multidetector computed tomography diagnosis and cine imaging of left main
      coronary arterial dissection.
AB  - Coronary artery dissection (CD) is a rare cause of acute myocardial ischemia. It
      is often diagnosed by invasive coronary angiography, which is the principal
      diagnostic tool and gold standard in the diagnosis and triage of patients with
      CD. More recently, electrocardiogram-gated multidetector computerized tomography
      has emerged as a complementary imaging tool primarily for follow-up purposes. To
      our knowledge, this is the first published report of the primary diagnosis and
      dynamic cine interrogation of a left main CD using retrospective
      electrocardiogram-gated multidetector computerized tomography, which was not
      disclosed on invasive coronary angiography.

PMID- 22627615
TI  - Reader variability in identifying pulmonary nodules on chest radiographs from the
      national lung screening trial.
AB  - PURPOSE: To measure reader variability related to the evaluation of screening
      chest radiographs (CXRs) for findings of primary lung cancer. MATERIALS AND
      METHODS: From the National Lung Screening Trial (NLST), 100 cases were randomly
      selected from baseline CXR examinations for retrospective interpretation by 9
      NLST radiologists; images with noncalcified lung nodules (NCNs) or other
      abnormalities suspicious for lung cancer as determined by the original NLST
      reader were oversampled. Agreement on the presence of pulmonary nodules and
      abnormalities suspicious for cancer and recommendations for follow-up were
      assessed by the multirater kappa statistic. RESULTS: The multirater kappa
      statistic for interreader agreement on the presence of at least 1 NCN was 0.38.
      Rates at which readers reported the presence of at least 1 NCN ranged from 32% to
      63% (mean, 41%); among 16 subjects with NCN and a cancer diagnosis within 1 year
      of the CXR examination, an average of 87% (range, 81% to 94%) of cases were
      classified as suspicious for cancer across all readers. The multirater kappa for
      agreement on follow-up recommendations was 0.34; pairwise kappa values ranged
      from 0.15 to 0.64 (mean, 0.36). For all subjects, readers recommended a follow-up
      procedure classified as high level (computed tomography, fluorodeoxyglucose
      positron emission tomography, or biopsy) 42% of the time on average (range, 30%
      to 67%); this increased to 84% (range, 52% to 100%) when readers reported an NCN
      and 88% (range, 82% to 94%) for subjects with cancer. CONCLUSION: Reader
      agreement for screening CXR interpretation and follow-up recommendations is fair
      overall but is high for malignant lesions.

PMID- 22627616
TI  - Quantitative analysis of motion artifacts in high-pitch dual-source computed
      tomography of the thorax.
AB  - PURPOSE: The purpose of this study was to objectively analyze motion artifacts on
      thoracic computed tomography (CT) with dual-source high-pitch and single-source
      techniques when using a no-breath-hold technique to examine patients who have
      difficulty complying with breath-holding instructions. MATERIALS AND METHODS: A
      total of 120 patients who received CT of the thorax with a free-breathing
      technique in single-source (16 slices and 128 slices; pitch = 1.2) and dual
      source (pitch = 3.0) manners were evaluated retrospectively. In each of the 3
      study groups, movements of the diaphragm and pulsations of the aortic root and
      main pulmonary artery were analyzed for their number and severity (blurred
      distance). RESULTS: No motion artifacts of the diaphragm were identified using a
      pitch of 3.0 (compared with n = 14 for single-source CT using 128 slices and n =
      24 using 16-slice CT). In single-source examinations, the severity of artifacts
      was similar between 128-slice CT and 16-slice CT: blurring distance of the lung
      parenchyma due to diaphragm movements was 14 versus 16 mm, and double contours of
      the aorta were measured as 8 and 9 mm, respectively. CONCLUSIONS: A high-pitch,
      dual-source mode is potentially advantageous for evaluating the lung parenchyma
      and vascular structures in patients who have difficulty complying with breath
      holding instructions. Increasing from 16 to 128 slices can significantly reduce
      the number and severity of motion artifacts.

PMID- 22627617
TI  - Are names of children with attention deficit hyperactivity disorder more
      'hyperactive'?
AB  - BACKGROUND: The role of the meaning of given names has been noted in
      psychotherapy as well as in everyday life. This study aimed to investigate the
      possible association between the nature of given names of children and attention
      deficit hyperactivity disorder (ADHD) diagnosis. SAMPLING AND METHODS: A total of
      134 given names of children and adolescent patients diagnosed as having ADHD were
      compared with those of an age- and gender-matched randomly chosen control group
      from the general population. The first names of the two cohorts were compared
      with regard to the following: the literal meaning of their names, whether the
      name constitutes a verb, the prevalence of each name and their length (number of
      syllables). RESULTS: The meaning of first names of children and adolescents with
      ADHD combined type were rated by referees as expressing significantly more
      activity and containing less syllables than the names of controls. In addition,
      the prevalence of their names was significantly lower than that of names used in
      the general population. All findings remained significant following Bonferroni
      adjustment. CONCLUSIONS: Our findings demonstrate an intriguing relationship
      between children's given names and ADHD diagnosis. Given names may serve as a
      possible predictor of later diagnosis of ADHD. Clinicians should be more
      attentive to given names in the context of child psychiatric evaluation and
      therapy.

PMID- 22627618
TI  - Monitoring of selected pesticides residue levels in water samples of paddy fields
      and removal of cypermethrin and chlorpyrifos residues from water using rice bran.
AB  - Consumption of pesticides associated foods increased in recent decades in
      Bangladesh. Most of the pesticides come from paddy, as rice is the main food
      items here and about 70 % pesticides are used only on paddy fields. Water samples
      of paddy fields and Kaliganga River of Manikganj district were analyzed to
      provide base line data on cypermethrin, chlorpyrifos and diazinon residue by
      using high performance liquid chromatography. Levels of Cypermethrin,
      chlorpyrifos and diazinon detected in the paddy field water samples were (0.605
      +/- 0.011 MUg/L), (0.06 +/- 0.001 MUg/L) and (0.039 +/- 0.002 MUg/L),
      respectively. 0.11 +/- 0.003 MUg/L of cypermethrin and 0.012 +/- 0.0006 MUg/L of
      chlorpyrifos were also identified in the water samples of Kaligonga River.
      Diazinon residue was not detected in the river water samples. The detected
      concentrations of pesticide residues in the river water were below the accepted
      maximum residue limit (MRL) value of drinking water (0.1 MUg/l) adopted by the
      FAO/WHO Codex Alimentarius Commission. Cypermethrin and chlorpyrifos were chosen
      for decontamination through rice bran, as it was found in river water. Two gm
      rice bran could easily decontaminated 95.6 % and 96.4 % of cypermethrin and
      chlorpyrifos. The result of this study showed that pesticide residue was detected
      in water samples were below the MRLs value, which can easily be decontaminated
      through absorption of rice bran.

PMID- 22627619
TI  - A gold nanocage-CNT hybrid for targeted imaging and photothermal destruction of
      cancer cells.
AB  - This communication reports the design of a novel aptamer conjugated gold nanocage
      decorated SWCNTs hybrid nanomaterial for targeted imaging and selective
      photothermal destruction of the prostate cancer cells.

PMID- 22627623
TI  - Late treatment of tuberculosis-associated kyphosis: literature review and
      experience from a SRS-GOP site.
AB  - INTRODUCTION: Spinal tuberculosis (TB) accounts for approximately half of all
      cases of musculoskeletal tuberculosis. Kyphosis is the rule in spinal
      tuberculosis and has potential detrimental effects on both the spinal cord and
      pulmonary function. Late-onset paraplegia is best avoided with the surgical
      correction of severe kyphosis, where at the same time anterior decompression of
      the cord is performed and the remnants of the tuberculosis-destroyed vertebral
      bodies are excised. MATERIAL AND METHODS: Review of the literature on late
      surgical treatment of TB-associated kyphosis; description and comparative
      analysis of the different surgical techniques. RESULTS: Kyphosis can be corrected
      either at the acute stage or at the healed late stage of tuberculous infection.
      In the late stage, the stiffness of the spine and chronic lung disease are
      additional considerations for the surgical approach and technique. Contrary to
      the traditional anterior transpleural approach used in the acute spinal
      tuberculosis infection, extrapleural approaches, either antero-lateral or direct
      posterior, are favored in late treatment. CONCLUSION: The correction of deformity
      is only feasible with three-column osteotomies, and posterior vertebral column
      resection (PVCR) is the treatment of choice in extreme kyphosis. The prognosis of
      the neurologic deficit (late paraplegia) is dependent on the extent of gliosis of
      the spinal cord.

PMID- 22627625
TI  - Basic psychological need satisfaction in leisure activities and adolescents' life
      satisfaction.
AB  - Participation in leisure activities is an important arena for the positive
      psychological development of adolescents. The present study set out to examine
      the relationship between adolescents' satisfaction of the psychological needs for
      competence, relatedness, and autonomy in their participation in leisure
      activities and their perceived life satisfaction. The aim was to identify the
      extent to which satisfaction of the three needs explained the relationship
      between participation in leisure activities and life satisfaction. These proposed
      mechanisms were based on previous empirical work and the theoretical frameworks
      of self-determination theory, and were tested in a nationally representative
      sample of Norwegian adolescents (N = 3,273) aged 15 and 16 years (51.8 % boys).
      The structural equation analysis showed that competence and relatedness
      satisfaction fully mediated the association between participation in activities
      and life satisfaction. Autonomy satisfaction had a direct positive effect on life
      satisfaction but did not show any mediation effect. The positive processes of
      psychological need satisfaction, and especially the need for competence and
      relatedness, experienced in the leisure activity domain thus seem to be
      beneficial for adolescents' well-being. These findings add to previous research
      investigating the positive impact of need satisfaction in other important domains
      in the lives of children and adolescents.

PMID- 22627624
TI  - Acculturation, enculturation, and symptoms of depression in Hispanic youth: the
      roles of gender, Hispanic cultural values, and family functioning.
AB  - The risk for depression increases as Hispanic youth acculturate to U.S. society.
      This association is stronger for Hispanic girls than boys. To better understand
      the influence of culture and family on depressive symptoms, we tested a process
      oriented model of acculturation, cultural values, and family functioning. The
      data came from Project RED, which included 1,922 Hispanic students (53 % girls;
      86 % were 14 years old; and 84 % were U.S. born) from Southern California. We
      used data from 9th to 11th grade to test the influence of acculturation-related
      experiences on depressive symptoms over time. Multi-group structural equation
      analysis suggested that both family conflict and cohesion were linked with
      depressive symptoms. Hispanic cultural values were associated with family
      cohesion and conflict but the strength and direction of these relationships
      varied across cultural values and gender. For girls and boys, familismo and
      respeto were associated with higher family cohesion and lower family conflict.
      Moreover, gender roles were linked with higher family cohesion in girls but not
      in boys. These results indicate that improving family functioning will be
      beneficial for boys' and girls' psychological well-being. This may be achieved by
      promoting familismo and respeto for boys and girls and by promoting traditional
      gender roles for girls.

PMID- 22627627
TI  - Association between the proportion of sclerotic glomeruli and serum creatinine in
      primary focal segmental glomerulosclerosis.
AB  - OBJECTIVE: To evaluate the possible correlation between the extent of sclerotic
      glomeruli and the level of serum creatinine and its clearance rate in patients
      with primary focal segmental glomerolusclerosis. MATERIAL AND METHOD: In a cross
      sectional study, 50 patients with biopsy-proven primary focal segmental
      glomerolusclerosis were recruited. The proportion of globally and segmentally
      sclerosed glomeruli was determined during the first histopathological examination
      of renal biopsy specimens. Correlations of these variables with on admission
      serum level of creatinine and its clearance rate were investigated. RESULTS:
      Twenty-four males and 26 females with a mean age of 39.82+/-16.45 (range: 16-85)
      years were enrolled in the study. In a significant fashion, the proportions of
      segmental and global glomerulosclerosis were directly correlated with the serum
      level of creatinine and inversely with its clearance rate (r=-0.43 with p=0.002
      and r=-0.45 with p=0.001, respectively). CONCLUSION: Apart from the degree of
      interstitial fibrosis, the serum level of creatinine and its clearance rate are
      well correlated with the proportions of both segmentally and globally sclerosed
      glomeruli in primary focal segmental glomerulosclerosis.

PMID- 22627626
TI  - Evidence of ambiguous differentiation and mTOR pathway dysregulation in
      subependymal giant cell astrocytoma.
AB  - OBJECTIVE: The exact cell of origin of subependymal giant cell astrocytoma is
      debated but most currently consider the tumor in the astrocytic category.
      Mutations and subsequent biallelic inactivation of TSC1 encoding hamartin, or
      TSC2 encoding tuberin appear to be the underlying genetic aberrations.
      Inactivation leads to loss of proteins that inhibit mammalian target of rapamycin
      (mTOR ) disrupting tightly regulated cell functions. MATERIAL AND METHOD: We
      analyzed the expression of tuberin and hamartin along with an array of
      neuroepithelial markers in 9 subependymal giant cell astrocytomas. In addition,
      RPS6 and 4EBP1 regulatory proteins that are downstream in the mTOR pathway were
      also evaluated. RESULTS: While hamartin and tuberin expression levels were
      relatively decreased compared to control tissue, this was not of particular
      practical use to detect the mutated gene since low levels of positivity could be
      detected throughout the central nervous system. As expected, the levels of RPS6
      and 4EBP1 were increased, further confirming the activation of the mTOR pathway.
      GFAP was positive in 5 cases, while Synaptophysin positivity was found in all
      tumors. CD34 (a marker often observed in well differentiated glio-neuronal
      tumors), Olig2 (a nuclear marker present in most gliomas), IDH1 and IDH2 were
      entirely negative in all tumor cells. Ki67 (MIB-1) showed a low proliferation
      rate ranging from 2% to 8%. CONCLUSION: Staining with neuroepithelial markers
      supports the suggestion of ambiguous differentiation. Subependymal giant cell
      astrocytomas do not appear to have the typical expression profiles of astrocytic
      tumors, under which they have been classified.

PMID- 22627628
TI  - The relationship between the stromal mast cell number, microvessel density, c
      erbB-2 staining and survival and prognostic factors in colorectal carcinoma.
AB  - OBJECTIVE: Colorectal adenocarcinomas take second place among the causes of death
      from carcinoma, and account for 98% of colorectal carcinomas. There is a need to
      determine new prognostic factors because of high frequency and significance.
      MATERIAL AND METHOD: 204 colorectal carcinomas diagnosed between 01.01.2005 -
      31.12.2008 at Uludag University Medical Faculty Pathology Department were studied
      for Factor VIII and c-erbB-2 immunohistochemically and with toluidine blue stain
      histochemically. Association of mast cell number, microvessel density, and c-erbB
      2 staining pattern with survival and known prognostic factors was evaluated.
      RESULTS: Follow-up period was 4-60 months. A total of 111 cases were alive, and
      65 had died. The mean number of mast cells was 8.00 (1-21) and the mean density
      of microvessels was 10.00 (2-21). Five-year survival rate of the mast cell group
      was 48.3% for values under 10 and 57.9% for values of 10 and higher. Five-year
      survival rate was 58.2% in the group with a microvessel density of 10 and above
      and 45.9% for values under 10. Five-year survival rate was 53.9% for the group
      with c-erbB-2 cytoplasmic staining and 48.2% for the group with membranous
      staining. CONCLUSION: The grade increased with the number of mast cells, while
      survival decreased with an increase in the number of mast cells. The ratio of c
      erbB-2 staining increased as the grade and stage increased. There was an
      association between mast cell number and microvessel density. We found no
      relationship between prognosis and c-erbB-2, mast cell number, and microvessel
      density.

PMID- 22627629
TI  - The expression of p53 and COX-2 in basal cell carcinoma, squamous cell carcinoma
      and actinic keratosis cases.
AB  - OBJECTIVE: The aim of this study was to investigate p53 and COX-2 expressions in
      basal cell carcinoma, squamous cell carcinoma and actinic keratoses, and to
      determine a possible relationship. MATERIAL AND METHOD: 50 basal cell carcinoma,
      45 squamous cell carcinoma and 45 actinic keratosis cases were evaluated. The
      type of tumor in basal cell carcinoma and tumor differentiation in squamous cell
      carcinoma were noted and the paraffin block that best represented the tumor was
      chosen. Immunostaining by p53 and COX-2 was performed on sections of the paraffin
      blocks. RESULTS: p53 expression was observed in 98% of basal cell carcinoma,
      88.9% of squamous cell carcinoma and all actinic keratosis cases. p53 expression
      was also noted in non-dysplastic appearing epithelium in actinic keratosis cases.
      COX-2 expression was seen in 90, 100 and 88.9% of the basal cell carcinoma,
      squamous cell carcinoma and actinic keratosis groups, respectively. Skin
      appendages, inflammatory cells and vascular structures were also stained by COX-2
      besides tumor tissue. COX-2 expression increased by the p53 expression increase
      in basal cell carcinoma and squamous cell carcinoma. p53 and COX-2 expressions
      were not related in terms of tumor type in the BCC and were not related in terms
      of differentiation in SCC. CONCLUSION: The existence of p53 expression in actinic
      keratosis cases has supported the idea that p53 plays a role in the early steps
      of carcinogenesis in skin cancers. The fact that the expression of COX-2
      increases in line with the increase of p53 expression in basal cell carcinoma and
      squamous cell carcinoma cases indicates that COX-2 expression may be affected by
      p53.

PMID- 22627630
TI  - Analysis of IMP3 expression in prostate adenocarcinomas.
AB  - OBJECTIVE: Prostate cancer is the second most common cause of male cancer deaths
      after lung cancer in developed countries. The prognostic factors currently
      identified for prostate carcinoma include preoperative serum PSA, TNM staging
      system, histological grade and surgical margin status and are composed of the
      clinically most important and useful parameters. However, all the markers studied
      have not been applied in clinical practice. The oncofetal protein Insulin-Like
      Growth Factor II has been demonstrated to be associated with aggressive tumor
      behavior in many organs including urothelial tumors and renal cell carcinoma. Our
      aim was to investigate the expression status of Insulin-Like Growth Factor II in
      benign prostate glands, high grade PIN and prostate adenocarcinoma, and to
      determine the role of Insulin-Like Growth Factor II in pathogenesis of prostate
      adenocarcinoma. MATERIAL AND METHOD: A total of 70 prostate adenocarcinoma cases
      accompanied by high grade PIN and benign prostate glands were evaluated by
      immunohistochemistry for the expression of Insulin-Like Growth Factor II.
      RESULTS: Insulin-Like Growth Factor II expression was not seen in any of the 70
      prostate adenocarcinoma and high grade PIN cases and benign prostate glands.
      CONCLUSION: Although the number of our cases was limited, our results suggested
      that Insulin-Like Growth Factor II protein expression was not included in the
      pathogenesis of the prostate adenocarcinomas and Insulin-Like Growth Factor II
      expression status cannot be used for diagnosis of prostate adenocarcinomas.

PMID- 22627631
TI  - Metaplastic breast carcinomas and their relationship with basal-like phenotype.
AB  - OBJECTIVE: Metaplastic carcinoma is a rare tumor showing high histological grade
      and low hormone receptor expression. It has pure epithelial and mixed types.
      Studies have suggested that metaplastic carcinomas may have a basal-like profile.
      Our aim was to evaluate the clinicopathological features of 11 metaplastic
      carcinomas and determine their resemblance to basal-like breast carcinomas
      regarding their morphological and immunohistochemical profile. MATERIAL AND
      METHOD: Eleven metaplastic carcinoma cases were reviewed for their
      histopathological features. All tumors but one were evaluated for the
      immunohistochemical expressions of the cytokeratin 5/6, cytokeratin 14 and
      epidermal growth factor receptor; and hormonal status was assessed. RESULTS: Four
      of eleven cases were carcinoma with chondroid metaplasia, 3 were adenosquamous
      carcinoma, 2 were squamous cell carcinoma and 2 were carcinosarcoma. The mean
      patient age was 53 years and the mean tumor size was 5,1 cm. Histological grade
      was 3 for all with a nuclear grade of 3. Average mitotic count was 31/10 high
      power fields. Four cases had a central scar, 5 had central necrosis and 7 had
      geographic necrosis. Tumor growth pattern was pushing in 6 cases and no carcinoma
      in-situ was identified in 5 cases. Seven of 10 patients had axillary lymph node
      metastasis. Seven of 10 cases were triple-negative (estrogen receptor-,
      progesterone receptor-, HER2-) and 6 of them were positive for cytokeratin 5/6
      and/or epidermal growth factor receptor, consistent with basal-like
      immunophenotype. Cytokeratin 14 was positive in 7 cases. CONCLUSION: Metaplastic
      carcinomas are large-sized, high-grade tumors with prominent nuclear pleomorphism
      and frequent mitosis. They rarely overexpress hormone receptors and HER2 and
      generally have basal-like immunophenotype.

PMID- 22627632
TI  - Efficacy of bronchial brush cytology and bronchial washings in diagnosis of non
      neoplastic and neoplastic bronchopulmonary lesions.
AB  - OBJECTIVE: The present study is based on the cytologic evaluation of bronchial
      brushings for the diagnosis of non neoplastic and neoplastic bronchopulmonary
      lesions and relation of the cytologic findings with clinical diagnosis and
      histopathologic examination wherever possible. MATERIAL AND METHOD: 35
      symptomatic patients were selected on whom bronchoscopy was done. Bronchial
      brushing was performed using straight brushes and bronchial washing specimens
      were collected after brushing samples. Smears were stained by Pap, H&E, and
      Giemsa in all the cases while PAS and Ziehl Neelsen stainings were done in
      selected cases. Endobronchial biopsy was performed using a flexible long biopsy
      forceps. RESULTS: The age of the patients varied from 18 to 88 years, and the
      male:female ratio was 3.3:1. Carcinoma was diagnosed in 21 (60%) out of total 35
      cases on bronchial biopsy and the remaining 14 cases (40%) showed inflammatory,
      tuberculous or no significant pathology. Bronchial washing showed 10 true
      positive, 10 true negative, 4 false positive and 11 false negative cases whereas
      bronchial brushing showed 17 true positive, 12 true negative, 2 false positive
      and 4 false negative cases as confirmed on biopsy. Bronchial brushing showed good
      sensitivity (80.9%) and specificity (85.7%) compared to bronchial washing which
      had sensitivity of 47.6% and specificity of 71.4%. CONCLUSION: These findings
      attempted to confirm the concept that pulmonary cytology has improved to the
      point that its sensitivity is high enough to justify its use as a definitive
      diagnostic tool in those cases in which tissue diagnosis is not possible.

PMID- 22627633
TI  - Placental ultrastructural changes and apoptosis in pregnancies with meconium
      stained amniotic fluid.
AB  - OBJECTIVE: The cause of meconium stained amniotic fluid in term healthy
      pregnancies is not clearly understood yet. The aim of this study was to
      investigate the placental ultrastructural changes and placental apoptosis in
      pregnancies complicated with meconium stained amniotic fluid. MATERIAL AND
      METHOD: The study group was composed of mothers (n: 13) and their term,
      appropriate for gestational age newborns with meconium stained amniotic fluid but
      without meconium aspiration syndrome. The control group consisted of mothers (n:
      24) and their term appropriate for gestational age babies. We studied placental
      ultrastructural changes by transmission electron microscopy and placental
      apoptosis by transmission electron microscopy and the TUNEL method. RESULTS: The
      incidence of placental apoptosis by the TUNEL method was significantly higher in
      the study group compared to the control group. Transmission electron microscopy
      investigation revealed more remarkable ultrastructural changes in the study group
      compared to the control group. CONCLUSION: The increased apoptosis and
      ultrastructural findings in placentas with meconium stained amniotic fluid may be
      related to the placental adaptation to the hypoxic fetuses.

PMID- 22627634
TI  - Evaluation of fetal autopsy findings in the Hatay region: 274 cases.
AB  - OBJECTIVE: The aim of this study was to present the incidence of fetal anomalies
      in our region of Hatay, Turkey in order to determine the efficiency of prenatal
      diagnosis through fetal autopsy, and to compare our statistical data with other
      national and international studies. MATERIAL AND METHOD: This study was conducted
      on 274 fetuses from terminated pregnancies due to abnormal prenatal findings and
      intrauterine deaths from 2005 to September 2010. Fetuses were evaluated through
      postmortem examination, external measurements, X-rays, Magnetic Resonance Images,
      Multislice Computerized Tomography and photographs. The autopsy was completed by
      the histological examination of each organ. RESULTS: Autopsy was conducted on 274
      fetuses. A fetal anomaly was detected in 160 (58.39%) cases. The central nervous
      system contained the most frequent structural defects (79 cases, 49.38%),
      followed by malformations in the musculoskeletal system in 36 cases (22.5%). The
      most frequent multiple system anomalies were central nervous system defect and
      bilateral adrenal agenesis, musculoskeletal system malformations and urinary
      system defects. Fetal autopsy provided additional findings in 43 cases (26.88%).
      CONCLUSION: Fetal autopsy is a very important procedure and an integral part of
      the general prenatal management. New findings through this method may suggest
      invaluable data for parents about potential risks in future pregnancies.

PMID- 22627635
TI  - [Angiomyxoma: always myxoid, sometimes aggressive].
AB  - Angiomyxoma is a distinct soft tissue tumor characterized by the presence of    
      prominent myxoid matrix and numerous thin-walled blood vessels. This tumor has a 
      predilection for the trunk, head and neck, extremities, and genitalia. It is a
      benign tumor and total excision is curative. Recurrence is rare except for   
      aggressive angiomyxomas. A 12-year-old girl with a 10-year history of a    
      subcutaneous mass on the left gluteus measuring 4.5x4x3 cm had been referred.    
      The tumor was encapsulated and was located in the reticular dermis and    
      subcutaneous tissue, composed of stellate cells with mucinous stroma.     Thin
      walled blood vessels were prominent. Immunohistochemically, tumor cells     were
      immunoreactive for vimentin. No immunoreactivity was present for estrogen    
      receptor, CD34, smooth muscle actin, S-100 protein and desmin. The purpose of    
      this report is to present a classical example of an isolated superficial    
      angiomyxoma and discuss the differential diagnosis, because of its relatively    
      infrequent occurence.

PMID- 22627636
TI  - Primary paratesticular ganglioneuroma: a rare case in an adult.
AB  - Ganglioneuroma is a benign tumor, affecting the central nervous system, commonly 
      seen in children and young adults. Non-cranial ganglioneuromas are seen    
      predominantly in the posterior mediastinum and retroperitoneum. Paratesticular   
      neoplasms are extremely rare and are susceptible to clinical misinterpretation  
      as malignancy. Tumors of nerve origin are a rarity in the paratesticular
      region,     with a few cases of schwannoma and malignant peripheral nerve sheath
      tumor being     reviewed in the literature. A rare case of ganglioneuroma
      involving the     paratesticular region in an adult is presented.

PMID- 22627637
TI  - Angiomyofibroblastoma-like tumor of the scrotum: a case report and review of
      literature.
AB  - Angiomyofibroblastoma-like tumor is a rare mesenchymal tumor of men. It commonly 
      occurs during the fifth to eighth decades of life and mainly involves the    
      inguinoscrotal region. It is derived from perivascular stem cells and has    
      capacity of lipoid and myofibroblastic differentiation. Histopathologically this 
      tumor in the male genitalia mimics female angiomyofibroblastoma but there are 
      morphological and immunohistochemical differences between these lesions. We   
      report a case of an angiomyofibroblastoma-like tumor that arose in the scrotal  
      region in a 40-year-old man.

PMID- 22627638
TI  - Periosteal chondroma of the ischium; an unusual location.
AB  - Periosteal chondroma is a rare benign tumor of hyaline cartilage. Periosteal    
      chondroma arising in the ischium is an extremely rare event. By presenting this  
      case report, we aim to remind that differential diagnosis of these lesions    
      should be carefully performed especially for unusual locations. A 51-year-old    
      man visited the orthopedics clinic with the complaints of left pelvic mass and   
      pain lasting about one year. Computed tomography showed a solid mass with    
      abundant specks of calcification that was 4x5 cm in diameter and associated with 
      the ischium of the left pelvic bone. There was no evidence of penetration into
      the medullary cavity and cortical sclerosis. No radiological aggressive    
      appearance was observed. The lesion was removed with the covering periosteum.    
      Microscopically, there were lobules of hyaline cartilage composed of    
      chondrocytes with foci of endochondral ossification and calcification. The case  
      was reported as 'periosteal chondroma'. In conclusion, this case     report
      presents a case of periosteal chondroma, a rare tumor, which occurred in     an
      unusual location and age range. The differential diagnosis of periosteal    
      chondroma from malignant lesions is necessary for avoiding aggressive and    
      inappropriate treatment.

PMID- 22627639
TI  - A rare parasitic infection in Turkey: schistosomiasis. Case report.
AB  - Schistosomiasis is a water-borne parasitic disease. It is endemic in tropical    
      and subtropical countries mainly in Africa and the eastern Mediterranean region. 
      We report a case of a 37-year-old male who attended our hospital for terminal 
      hematuria and irritative voiding symptoms. Schistosoma haematobium eggs were  
      found in his urine sediment. He underwent transurethral resection of the    
      bladder. Pathological study confirmed the existence of vesical schistosomiasis.  
      S. haematobium cases are rarely seen in Turkey. Epidemiological and clinical   
      significance of S. haematobium has been discussed.

PMID- 22627640
TI  - [Clear cell mucoepidermoid carcinoma of the parotid gland: a case report].
AB  - Clear cell variant of mucoepidermoid carcinoma of the salivary glands is rare. A 
      55-year-old male patient with recently growing left parotid mass underwent    
      superficial parotidectomy. Although the dominant component of the tumor was    
      composed of clear cells, mucin containing cells were also present.    
      Histochemically, alcian blue stain supported intracellular mucin positivity.    
      Immunohistochemically, p63 was positive. Based on the morphological,    
      histochemical and immunohistochemical findings, the case was diagnosed as    
      mucoepidermoid carcinoma, clear cell variant.

PMID- 22627641
TI  - A case of pure endophytic squamous cell carcinoma of the gallbladder: a rare
      entity with aggressive behaviour.
AB  - Pure squamous cell carcinoma of gallbladder is a rare tumor accounting for only
      3% of the malignancies of gallbladder. A 35-year-old female presented with pain
      and lump in right hypochondrium. Ultrasonography and computed tomography revealed
      a thickened gallbladder filled with stones without any obvious growth and a large
      hepatic mass. Histologically, a pure type of well differentiated squamous cell
      carcinoma of gallbladder was diagnosed after excluding all possible differential
      diagnoses owing to different histogenesis and aggressive biological behaviour.
      Early diagnosis is the most important parameter for improving the survival
      indices among the patients with squamous cell carcinoma of the gallbladder.

PMID- 22627642
TI  - Clinical, histopathological and mineralogical analysis findings of an unusual
      case of pneumoconiosis.
AB  - A 43-year-old man with a long history of dyspnea which had progressively    
      worsened over the preceding month is presented. He had worked in an antimony    
      mine for 3 years. Radiologically, there were diffuse reticulonodular shadowing   
      opacities in both lung parenchymas. Histopathologic examination of the open-lung
      biopsy specimen revealed alveolar spaces filled with dust-laden macrophages
      and     amorphous proteinaceous semifluid, the latter being immunoreactive for
      Human     Surfactant Apoprotein A, associated with marked interstitial
      accumulation of the     similar-looking macrophages along the bronchovascular
      bundles and mild     interstitial fibrosis. Silicotic nodules or mixed dust
      fibrosis were not seen.     The patient was diagnosed as silicoproteinosis with
      unusual histopathological     features because he had worked in an antimony mine
      for only 3 years and had 86%     silica in a mineralogical analysis.
      Pneumoconiosis is a rare lung disease which     may be confused with other
      interstitial lung diseases. Clinical, radiological     and unusual
      histopathologic features of this rare case are presented and     discussed with
      the differential diagnosis, especially of mixed dust     pneumoconiosis.

PMID- 22627643
TI  - Impact on carbon footprint: a life cycle assessment of disposable versus reusable
      sharps containers in a large US hospital.
AB  - Hospitals are striving to reduce their greenhouse gas (GHG) emissions. Targeting
      supply chain points and replacing disposable with reusable items are among
      recommendations to achieve this. Annually, US hospitals use 35 million disposable
      (DSC) or reusable sharps containers (RSC) generating GHG in their manufacture,
      use, and disposal. Using a life cycle assessment we assessed the global warming
      potential (GWP) of both systems at a large US hospital which replaced DSC with
      RSC. GHG emissions (CO(2), CH(4), N(2)O) were calculated in metric tons of CO(2)
      equivalents (MTCO(2)eq). Primary energy input data was used wherever possible and
      region-specific conversions used to calculate the GWP of each activity. Unit
      process GHGs were collated into manufacture, transport, washing, and treatment
      and disposal. The DSC were not recycled nor had recycled content. Chemotherapy
      DSC were used in both systems. Emission totals were workload-normalized per 100
      occupied beds-yr and rate ratio analyzed using Fisher's test with P <=0.05 and
      95% confidence level. With RSC, the hospital reduced its annual GWP by 127
      MTCO(2)eq (-83.5%) and diverted 30.9 tons of plastic and 5.0 tons of cardboard
      from landfill. Using RSC reduced the number of containers manufactured from
      34,396 DSC annually to 1844 RSC in year one only. The study indicates sharps
      containment GWP in US hospitals totals 100,000 MTCO(2)eq and if RSC were used
      nationally the figure could fall by 64,000 MTCO(2)eq which, whilst only a
      fraction of total hospital GWP, is a positive, sustainable step.

PMID- 22627644
TI  - Possible environmental impacts of recycled glass used as a pavement base
      material.
AB  - In theory, glass diverted or recovered from the municipal solid waste (MSW)
      stream can be used as feedstock (glass cullet) in the production of new glass
      containers. However, post-consumer glass typically contains a mixture of clear
      and coloured material and is often contaminated with other wastes;
      characteristics that are impediments to the production of new containers. Sorting
      and cleaning of glass diverted from MSW to make it feasible for use in bottle
      industries are also time consuming and costly tasks. There is, however, the
      potential to use recycled glass as a sub-base material for road pavement
      construction. Geotechnical investigations to date suggest that use of recycled
      glass as a roadway sub-base could be cost-effective, and thus preclude the need
      for expensive sorting. There is, however, the necessessity to further investigate
      the potential short- and long-term toxicity, health hazards, and/or environmental
      pollution associated with use of mixed glass cullet as an aggregate, considering
      conditions during stockpiled storage and after placement. The results of
      laboratory tests on recycled glass regarding its potential to release pollutants
      to the environment via leaching are presented herein. Five random samples of
      crushed glasses were collected from a recycling company in Melbourne, Australia.
      The parameters tested for each sample were total organic matter, heavy metals,
      sulfates, chlorides, conductivity, pH and surfactant levels. It wais found that
      in most cases, the contamination levels were within the State of Victoria's
      Environmental Protection Agency-specified limits for manual handling, thus
      indicating that recycled glass could probably be safely used in pavement sub
      bases.

PMID- 22627646
TI  - Stage I lung cancer survivorship: risk of second malignancies and need for
      individualized care plan.
AB  - BACKGROUND: Survivors of stage I lung cancer are at increased risk of subsequent
      malignancies. Specific data on risk of subsequent malignancies are underreported
      in the literature. We studied the incidence of stage I lung cancer and the
      incidence of all second malignancies in survivors. METHODS: Data from the
      Surveillance, Epidemiology and End Results 9 database were analyzed to calculate
      the incidence of stage I lung cancer and subsequent malignancies from 1998 to
      2007. The risk of subsequent malignancies is reported as a standardized incidence
      ratio (observed incidence [O]/expected incidence [E]). RESULTS: The incidence
      rate of stage I lung cancer increased slowly from 1988 (8, confidence interval
      [CI]: 7.6-8.4) to 2003 (9.2, CI: 8.9-9.6) and more rapidly from 2003 to 2007
      (11.2, CI: 10.8-11.7). The risk of developing a second lung cancer is highest in
      the first year with the O/E at 6.78 (CI: 6.29-7.31) and continues to be high at
      10 years (O/E 4.12; CI: 4.44-4.80). Laryngeal cancer has the highest incidence in
      the first year (O/E 9.78; CI: 7.51-12.51) and continues to be high at 10 years
      (O/E 3.55; CI: 1.77-6.34). For gastrointestinal cancers, there is increased risk
      of colon (O/E 1.33; CI: 1.22-1.44), esophagus (O/E 2.29; CI: 1.85-2.89), and
      stomach (O/E 1.43; CI: 1.15-1.75) cancers. The increased risk of bladder cancer
      (O/E 1.83; CI: 1.65-2.03) remains high even at 10 years after the diagnosis of
      stage I lung cancer. CONCLUSIONS: There is increasing incidence of stage I lung
      cancer. Survivors of stage I are at increased risk of certain second
      malignancies.

PMID- 22627647
TI  - Automated identification of patients with pulmonary nodules in an integrated
      health system using administrative health plan data, radiology reports, and
      natural language processing.
AB  - INTRODUCTION: Lung nodules are commonly encountered in clinical practice, yet
      little is known about their management in community settings. An automated method
      for identifying patients with lung nodules would greatly facilitate research in
      this area. METHODS: Using members of a large, community-based health plan from
      2006 to 2010, we developed a method to identify patients with lung nodules, by
      combining five diagnostic codes, four procedural codes, and a natural language
      processing algorithm that performed free text searches of radiology transcripts.
      An experienced pulmonologist reviewed a random sample of 116 radiology
      transcripts, providing a reference standard for the natural language processing
      algorithm. RESULTS: With the use of an automated method, we identified 7112
      unique members as having one or more incident lung nodules. The mean age of the
      patients was 65 years (standard deviation 14 years). There were slightly more
      women (54%) than men, and Hispanics and non-whites comprised 45% of the lung
      nodule cohort. Thirty-six percent were never smokers whereas 11% were current
      smokers. Fourteen percent of the patients were subsequently diagnosed with lung
      cancer. The sensitivity and specificity of the natural language processing
      algorithm for identifying the presence of lung nodules were 96% and 86%,
      respectively, compared with clinician review. Among the true positive transcripts
      in the validation sample, only 35% were solitary and unaccompanied by one or more
      associated findings, and 56% measured 8 to 30 mm in diameter. CONCLUSIONS: A
      combination of diagnostic codes, procedural codes, and a natural language
      processing algorithm for free text searching of radiology reports can accurately
      and efficiently identify patients with incident lung nodules, many of whom are
      subsequently diagnosed with lung cancer.

PMID- 22627648
TI  - Congenital anomalous origin of a single coronary artery and high-level sporting
      competition.
AB  - Using a single clinical case of a professional soccer player presenting an
      anomalous origin of the right coronary artery, cardiac screening and surgical
      treatment are described taking into account the recommendations of cardiac and
      sports societies.

PMID- 22627649
TI  - Changes in self-reported knee function and health-related quality of life after
      knee injury in female athletes.
AB  - OBJECTIVE: To document the changes in self-reported health-related quality of
      life and knee function in a cohort of young female athletes who have sustained a
      knee injury. DESIGN: Prospective cohort. SETTING: An outpatient sports medicine
      clinic and university student health service. PARTICIPANTS: A convenience sample
      of 255 females (age = 17.4 +/- 2.4 years) who injured their knee participating in
      sport or recreational activities. Injuries were categorized as anterior cruciate
      ligament tears, anterior knee pain, patellar instability, meniscus tear,
      collateral ligament sprain, and other. INTERVENTIONS: Knee function was assessed
      with the 2000 International Knee Documentation Committee (IKDC) knee survey.
      Health-related quality of life was assessed with the SF-12 version 2.0 (acute)
      survey (SF-12). MAIN OUTCOME MEASURES: Dependent variables included the paired
      differences in the 2000 IKDC and SF-12 subscales, and composite scores from
      preinjury to diagnosis. Paired differences were assessed with paired t tests (P <
      0.05) reported as the mean +/- SD. RESULTS: International Knee Documentation
      Committee scores at diagnosis were significantly lower than preinjury scores (P <
      0.001). SF-12 scores were lower (P < 0.001) at diagnosis for each subscale
      (physical functioning, role physical, bodily pain, general health, vitality,
      social function, role emotional, and mental health) as well as the physical and
      mental composite scores. CONCLUSIONS: In addition to negatively affecting knee
      function, sport medicine providers should be aware that knee injuries can
      negatively impact the health-related quality of life in these athletes
      immediately after injury.

PMID- 22627650
TI  - Osteochondritis dissecans of both knees, both elbows, and the first
      metatarsophalangeal joint in a female soccer player.
AB  - A 19-year-old female soccer player presented for evaluation of pain at the base
      of the right hallux after a recent sports injury. She had a history of 4
      operations, 1 each at both knees and both elbows, for the treatment of
      osteochondritis dissecans (OCD). Examination showed tenderness to palpation and
      limited range of motion of the first metatarsophalangeal (MP) joint, and
      radiographs showed stage 4 OCD of the first metatarsal head with a detached
      osseous fragment. Diagnostic arthroscopy confirmed the presence of OCD, and
      treatment included arthrotomy, excision of the loose body, and microfracture of
      the defect. Evaluation at 3 months after surgery showed that the first MP joint
      pain and limited motion had completely resolved, and the patient returned to
      soccer practice. Although OCD at 1 location is diagnosed frequently in athletes,
      involvement of 5 different joints in the same patient is uncommon.

PMID- 22627651
TI  - The effect of laryngoscope handle size on possible endotracheal intubation
      success in university football, ice hockey, and soccer players.
AB  - OBJECTIVE: To assess the effectiveness of a standard long-handle laryngoscope and
      a short-handle laryngoscope on ease of possible intubation in football, ice
      hockey, and soccer players. DESIGN: Prospective crossover study. SETTING:
      University Sport Medicine Clinic. PARTICIPANTS: Sixty-two university varsity
      football (62 males), 45 ice hockey (26 males and 19 females), and 39 soccer
      players (20 males, 19 females). INTERVENTIONS: Athletes were assessed for
      different airway and physical characteristics. Three different physicians then
      assessed the use of laryngoscopes of different handle sizes in supine athletes
      who were wearing protective equipment while in-line cervical spine immobilization
      was maintained. MAIN OUTCOME MEASURES: The ease of passage of a laryngoscope
      blade into the posterior oropharynx of a supine athlete was assessed using both a
      standard long-handle and a short-handle laryngoscope. RESULTS: Use of a short
      handle laryngoscope was easier for all physicians in all sports as compared with
      a standard-sized laryngoscope. Passage of a laryngoscope blade into the posterior
      oropharynx of a supine athlete was easiest in soccer players and most difficult
      in football and ice hockey players for both sizes of laryngoscope. Interference
      from chest or shoulder pads was a common cause for difficulty in passing the
      laryngoscope blade into the posterior oropharynx for football and ice hockey
      players. CONCLUSIONS: In the rare instances that an endotracheal intubation is to
      be attempted on an unconscious athlete, a short-handle laryngoscope may provide
      the best chance for successful intubation.

PMID- 22627652
TI  - Baseball and softball sliding injuries:  incidence and correlates during one high
      school league varsity season.
AB  - OBJECTIVE: To estimate injury rates associated with sliding in high school
      baseball and softball. DESIGN: Prospective cohort study. SETTING: Community high
      school athletic events. PARTICIPANTS: Ten high school varsity baseball and
      softball teams over 1 season. ASSESSMENT OF RISK FACTORS: All sliding attempts
      were recorded during each game and recorded as headfirst, feetfirst, or diveback.
      Base type, playing surface, and field conditions were also noted. MAIN OUTCOME
      MEASURES: Injury exposure rates by game exposures and sliding/diveback exposures.
      RESULTS: Data were collected from 153 baseball games and 166 softball games. A
      greater proportion of slides were associated with injury in softball than in
      baseball (42.0 and 4.9 per 1000 slides; P < 0.05). Headfirst slides led to more
      injuries than feetfirst slides in baseball (16.8 vs 0 per 1000 slides; P < 0.05)
      but not in softball (55 vs 35 per 1000 slides; P = 0.74). CONCLUSIONS: More
      powerful studies are required to determine whether efforts to prevent baseball
      sliding injuries at the high school level should focus on better education in
      sliding technique or changes in equipment. Softball players are vulnerable to
      injury when wearing inadequate protective sliding apparel.

PMID- 22627653
TI  - Systematic review and recommendations for intracompartmental pressure monitoring
      in diagnosing chronic exertional compartment syndrome of the leg.
AB  - OBJECTIVE: Although all intracompartmental pressure (ICP) measurement, magnetic
      resonance imaging, and near-infrared spectroscopy seem to be useful in confirming
      the diagnosis of chronic exertional compartment syndrome (CECS), no standard
      diagnostic procedure is currently universally accepted. We reviewed
      systematically the relevant published evidence on diagnostic criteria commonly in
      use for CECS to address 3 main questions: (1) Is there a standard diagnostic
      method available? (2) What ICP threshold criteria should be used for diagnosing
      CECS? (3) What are the criteria and options for surgical management? Finally, we
      made statements on the strength of each diagnostic criterion of ICP based on a
      rigorous standardized process. DATA SOURCES: We searched for studies that
      investigated ICP measurements in diagnosing CECS in the leg of human subjects,
      using PubMed, Score, PEDRO, Cochrane, Scopus, SportDiscus, Web of Knowledge, and
      Google Scholar. Initial searches were performed using the phrase, "chronic
      exertional compartment syndrome." The phrase "compartment syndrome" was then
      combined, using Boolean connectors ("OR" and "AND") with the words "diagnosis,"
      "parameters," "levels," "localisation," or "measurement." Data extracted from
      each study included study design, number of subjects, number of controls, ICP
      instrument used, compartments measured, limb position during measurements,
      catheter position, exercise protocol, timing of measurements, mean resting
      compartment pressures, mean maximal compartment pressures, mean postexercise
      compartment pressures, diagnostic criteria used, and whether a reference
      diagnostic standard was used. The quality of studies was assessed based on the
      approach used by the American Academy of Orthopaedic Surgeons in judging the
      quality of diagnostic studies, and recommendations were made regarding each ICP
      diagnostic criteria in the literature by taking into account the quality and
      quantity of the available studies proposing each criterion. MAIN RESULTS: In the
      review, 32 studies were included. The studies varied in the ICP measurement
      techniques used; the most commonly measured compartment was the anterior muscle
      compartment, and the exercise protocol varied between running, walking, and ankle
      plantarflexion and dorsiflexion exercises. Preexercise, mean values ranged from
      7.4 to 50.8 mm Hg for CECS patients, and 5.7 to 12 mm Hg in controls;
      measurements during exercise showed mean pressure readings ranging from 42 to 150
      mm Hg in patients and 28 to 141 mm Hg in controls. No overlap between subjects
      and controls in mean ICP measurements was found at the 1-minute postexercise
      timing interval only showing values ranging from 34 to 55.4 mm Hg and 9 to 19 mm
      Hg in CECS patients and controls, respectively. The quality of the studies was
      generally not high, and we found the evidence for commonly used ICP criteria in
      diagnosing CECS to be weak. CONCLUSIONS: Studies in which an independent, blinded
      comparison is made with a valid reference standard among consecutive patients are
      yet to be undertaken. There should also be an agreed ICP test protocol for
      diagnosing CECS because the variability here contributes to the large differences
      in ICP measurements and hence diagnostic thresholds between studies. Current ICP
      pressure criteria for CECS diagnosis are therefore unreliable, and emphasis
      should remain on good history. However, clinicians may consider measurements
      taken at 1 minute after exercise because mean levels at this timing interval only
      did not overlap between subjects and controls in the studies we analyzed. Levels
      above the highest reported value for controls here (27.5 mm Hg) along with a good
      history, should be regarded as highly suggestive of CECS. It is evident that to
      achieve an objective recommendation for ICP threshold there is a need to set up a
      multi-center study group to reach an agreed testing protocol and modify the
      preliminary recommendations we have made.

PMID- 22627654
TI  - Isolated axillary artery injury due to blunt trauma in ice hockey.
AB  - We report the first case of a purely isolated axillary artery dissection because
      of focal blunt trauma to the axilla. A 42-year-old man presented to our
      outpatient orthopedic clinic 7 days after a fall during a hockey game whereby
      another player's skate blade struck the patient directly in the axilla without
      disrupting the skin. The patient denied having any symptoms of shoulder
      dislocation but experienced some pain and numbness, which subsided rapidly. Then
      he developed a cool hand with exertional claudication. Physical examination
      revealed absent radial and brachial pulses. Computed tomographic angiography
      demonstrated dissection of the distal axillary artery extending to the middle two
      thirds of the brachial artery. Following urgent consultation with vascular
      surgery, the patient was treated operatively with reverse saphenous
      interpositional grafting and embolectomy. This case illustrates the need to have
      a heightened index of suspicion to all injuries to the axilla and the importance
      of performing careful soft tissue and neurovascular examinations in hockey
      players presenting with shoulder complaints, even when bony injury is not
      present.

PMID- 22627655
TI  - Prevention of child camel jockey injuries: a success story from the United Arab
      Emirates.
AB  - OBJECTIVE: To study the effects of a law banning children from taking part in
      camel racing on child camel jockey injuries in Al-Ain City, United Arab Emirates.
      DESIGN: Prospective study. SETTING: University Teaching Hospital. PATIENTS: All
      patients who were admitted to Al-Ain Hospital and were injured while riding
      camels were prospectively studied between January 1, 2002, and December 31, 2009.
      ASSESSMENT OF RISK FACTORS: Two periods, before the law and after its
      introduction, were compared. MAIN OUTCOME MEASURES: Pediatric injuries, their
      anatomical distribution, and severity of injury. RESULTS: Fifty-four patients
      were studied, and all were males. There were 13 children and 41 adults. All
      children were camel jockeys except 1 child who was riding a camel for fun. None
      of the adult camel riders was a camel jockey. The median (range) age of patients
      admitted before the law was 12.5 (5-45) years, which was significantly less
      compared with 27.2 (20-40) years after its introduction (P = 0.001, Mann-Whitney
      test). All 13 children sustained their injuries before the law was implemented,
      whereas 12 of 41 adults sustained their injuries before the legislation was in
      place (P < 0.0001, Fisher exact test). The total length of hospital stay of
      patients was significantly reduced after the law enforcement (P < 0.01, Mann
      Whitney test). CONCLUSIONS: Our findings emphasize the important role of law
      enforcement in injury prevention, illustrated by the replacement of children by
      robot substitutes. This is possibly one of the few examples where child injury
      has been completely prevented by legislation.

PMID- 22627656
TI  - Acute sacroiliac joint infection in a rugby player with atopic dermatitis.
AB  - In athletes, acute bacterial infection is an unusual cause of pain in the
      sacroiliac joint. Although an entry site for infection is not always evident, the
      present case of a 15-year-old rugby player suggests the association between right
      sacroiliac joint infection and skin lesion of atopic dermatitis (AD) infected
      with group A streptococcus. Magnetic resonance imaging revealed inflammation
      around the sacroiliac joint with abscess formation. The infection resolved after
      a course of antibiotics. Because atopic skin lesion is a potential portal of
      bacteria, treatment for AD is essential for the prevention of pyogenic arthritis
      in athletes.

PMID- 22627657
TI  - Costal cartilage fractures and disruptions in a rugby football player.
AB  - Costal cartilage fracture of the rib cage, or costochondral, is a rare sporting
      injury. For contact athletes, the instability of the rib cage may lead to
      potential serious complications, similar to rib fractures or thorax disruption.
      Most authors recommend initial conservative treatment with surgery reserved for
      only recalcitrant cases. We report a case of an amateur American male rugby
      football player who sustained a costal cartilage fracture and disruption
      involving the anterior left fifth and sixth rib costal cartilages. The case
      highlights the difficulty in establishing the diagnosis based on clinical
      examination and standard radiographs alone. Computed tomography was used to
      assist in diagnosing this destabilizing injury to the rib cage. Costal cartilage
      fractures and disruptions in athletes are rarely reported in the literature and
      can have serious implications for the athlete's ability to return to play if the
      rib cage is destabilized.

PMID- 22627658
TI  - Trends and factors associated with the Day 5 embryo transfer, assisted
      reproductive technology surveillance, USA, 2001-2009.
AB  - STUDY QUESTION: What characteristics are associated with a Day 5 embryo transfer?
      SUMMARY ANSWER: The use of the Day 5 embryo transfer has increased over time,
      with clinicians allowing women with typically 'poorer' prognostic characteristics
      to undergo a Day 5 embryo transfer. The mean number of embryos per Day 5 transfer
      decreased from 2001 to 2009, although the prevalence of the Day 5 single embryo
      transfer remains low and the rate of multiple births remains substantial. WHAT IS
      KNOWN AND WHAT THIS PAPER ADDS: Day 5 embryo transfer may reduce the rate of
      multiple gestation pregnancy. US trends over time in the prevalence of the Day 5
      transfer, changes in characteristics of patients receiving Day 5 transfer, and
      number of embryos transferred are unknown. DESIGN: We used 2001-2009 US National
      assisted reproductive technology (ART) Surveillance System (NASS) data on 620,295
      fresh IVF cycles derived from autologous oocytes with a Day 3 or 5 embryo
      transfer. Trends in the mean number of embryos transferred from 2001 to 2009 were
      assessed by the day of transfer. For 349,947 cycles from clinics performing both
      Days 3 and 5 embryo transfers, multivariable logistic regression was used to
      determine the characteristics associated with the Day 5 embryo transfer. We also
      compared the characteristics of the Day 5 embryo cycles in 2001 and 2009. MAIN
      RESULTS AND THE ROLE OF CHANCE: Overall, the proportion of ART cycles using the
      Day 5 embryo transfer increased from 12% in 2001 to 36% in 2009 (P<0.0001), while
      the mean number of embryos transferred decreased from 2.4 to 2.1 (P<0.0001).
      Among Day 5 transfers, the rate of the single embryo transfer tripled from 4.5%
      in 2001 to 14.8% in 2009 (P<0.0001); and the rate of multiple births decreased
      from 44.8 to 41.1% (P<0.0001). In cycles initiated after 2001, maternal age<35
      years, no prior ART cycles, >=1 prior pregnancies, baseline follicle stimulating
      hormone<10 international units and >=10 oocytes retrieved were associated with
      the Day 5 embryo transfer. Compared with 2001, in 2009, a broader range of
      candidates received the Day 5 transfer. BIAS Women undergoing multiple ART cycles
      over time are not linked. CONFOUNDING FACTORS AND OTHER REASONS FOR CAUTION: We
      ran multivariable logistic regression to lessen the effects of the confounding
      factors. Cycle cancelation rates by the day of embryo transfer are unknown.
      GENERALIZABILITY TO OTHER POPULATIONS: Generalizable to ART clinics included in
      NASS. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Centres for
      Disease Control. The authors have no competing interests to declare.

PMID- 22627659
TI  - MLPA and sequence analysis of DPY19L2 reveals point mutations causing
      globozoospermia.
AB  - STUDY QUESTION: Do DPY19L2 heterozygous deletions and point mutations account for
      some cases of globozoospermia? SUMMARY ANSWER: Two DPY19L2 heterozygous deletions
      and three point mutations were identified, thus further confirming that genetic
      alterations of the DPY19L2 gene are the main cause of globozoospermia and
      indicating that DPY19L2 molecular diagnostics should not be stopped in the
      absence of a homozygous gene deletion. WHAT IS KNOWN ALREADY: Globozoospermia is
      a rare phenotype of primary male infertility characterized by the production of a
      majority of round-headed spermatozoa without acrosome. We demonstrated previously
      that most cases in man were caused by a recurrent homozygous deletion of the
      totality of the DPY19L2 gene, preventing sperm head elongation and acrosome
      formation. In mammals, DPY19L2 has three paralogs of yet unknown function and one
      highly homologous pseudogene showing >95% sequence identity with DPY19L2.
      Specific amplification and sequencing of DPY19L2 have so far been hampered by the
      presence of this pseudogene which has greatly complicated specific amplification
      and sequencing. STUDY DESIGN, SIZE, DURATION: In this cohort study, 34 patients
      presenting with globozoospermia were recruited during routine infertility
      treatment in infertility centers in France and Tunisia between January 2008 and
      December 2011. The molecular variants identified in patients were screened in 200
      individuals from the general population to exclude frequent non-pathological
      polymorphisms. PARTICIPANTS/MATERIALS, SETTING, METHODS: We developed a Multiplex
      Ligation-dependent Probe Amplification test to detect the presence of
      heterozygous deletions and identified the conditions to specifically amplify and
      sequence the 22 exons and intronic boundaries of the DPY19L2 gene. The
      pathogenicity of the identified mutations and their action on the protein were
      evaluated in silico. MAIN RESULTS AND THE ROLE OF CHANCE: There were 23 patients
      who were homozygous for the DPY19L2 deletion (67.6%). Only eight of the eleven
      non-homozygously deleted patients could be sequenced due to poor DNA quality of
      three patients. Two patients were compound heterozygous carrying one DPY19L2
      deleted allele associated respectively with a nonsense (p.Q342*) and a missense
      mutation (p.R290H). One patient was homozygous for p.M358K, another missense
      mutation affecting a highly conserved amino acid. Due to the localization of this
      mutation and the physicochemical properties of the substituted amino acids, we
      believe that this variant is likely to disrupt one of the protein transmembrane
      domains and destabilize the protein. Overall, 84% of the fully analysed patients
      (n = 31) had a molecular alteration of DPY19L2. There was no clear phenotypic
      difference between the homozygous deleted individual, patients carrying a point
      mutation and undiagnosed patients. LIMITATIONS, REASONS FOR CAUTION: Globally
      poor fertilization rates are observed after intracytoplasmic sperm injection of
      round spermatozoa. Further work is needed to assess whether DPY19L2 mutated
      patients present a better or worse prognostic than the non-diagnosed patients.
      Evaluation of the potential benefit of treatment with a calcium ionophore,
      described to improve fertilization, should be evaluated in these two groups.
      WIDER IMPLICATIONS OF THE FINDINGS: In previous work, deletions of DPY19L2 had
      only been identified in North African patients. Here we have identified DPY19L2
      deletions and point mutations in European patients, indicating that
      globozoospemia caused by a molecular defect of DPY19L2 can be expected in
      individuals from any ethnic background. STUDY FUNDING/COMPETING INTEREST(S): None
      of the authors have any competing interest. This work is part of the project
      'Identification and Characterization of Genes Involved in Infertility (ICG2I)'
      funded by the program GENOPAT 2009 from the French Research Agency (ANR).

PMID- 22627660
TI  - Tricuspid valve repair: is ring annuloplasty superior?
AB  - OBJECTIVES: Tricuspid regurgitation (TR) secondary to left heart disease is the
      most common aetiology of tricuspid valve (TV) insufficiency. Valve annuloplasty
      is the primary treatment for TV insufficiency. Several studies have shown the
      superiority of annuloplasty with a prosthetic ring over other repair techniques.
      We reviewed our experience with different surgical techniques for the treatment
      of acquired TV disease focusing on long-term survival and incidence of
      reoperation. METHODS: A retrospective analysis of 717 consecutive patients who
      underwent TV surgery between 1975 and 2009 with either a ring annuloplasty [Group
      R: N = 433 (60%)] or a De Vega suture annuloplasty [Group NR: no ring; N = 255
      (36%)]. Twenty-nine (4%) patients underwent other types of TV repair. A ring
      annuloplasty was performed predominantly in the late study period of 2000-09. TV
      aetiology was functional in 67% (479/717) of the patients. Ninety-one percent of
      the patients (n = 649) underwent concomitant coronary artery bypass grafting
      and/or mitral/aortic valve surgery. RESULTS: Patients who received a ring
      annuloplasty were older (67 +/- 13 vs 60 +/- 13 years; P < 0.001). Overall 30-day
      mortality was 13.8% (n = 95) [Group R: n = 55 (12.7%) and Group NR: n = 40
      (15.7%)]. Ten-year actuarial survival after TV repair with either the De Vega
      suture or ring annuloplasty was 39 +/- 3 and 46 +/- 7%, respectively (P = 0.01).
      Twenty-eight (4%) patients required a TV reoperation after 5.9 +/- 5.1 years.
      Freedom from TV reoperation 10 years after repair with a De Vega annuloplasty was
      87.9 +/- 3% compared with 98.4 +/- 1% after the ring annuloplasty (P = 0.034).
      CONCLUSIONS: Patients who require TV surgery either as an isolated or a combined
      procedure constitute a high-risk group. The long-term survival is poor. Tricuspid
      valve repair with a ring annuloplasty is associated with improved survival and a
      lower reoperation rate than that with a suture annuloplasty.

PMID- 22627661
TI  - Preservation of right ventricular structure and function following transatrial
      transpulmonary repair of tetralogy of Fallot.
AB  - OBJECTIVES: Management strategy of patients with tetralogy of Fallot (TOF)
      including timing, as well as surgical technique-remains a controversial topic. We
      sought to analyse both early and late results of our consistent policy of non
      neonatal transatrial/transpulmonary (TA/TP) repair of TOF over almost 14 years,
      in order to assess preservation or possible deterioration of right ventricular
      (RV) function. METHODS: All 245 consecutive patients with TOF, referred to our
      group for repair between September 1997 and December 2010, have been
      prospectively followed up. Their clinical and echocardiographic data were
      retrospectively analysed. All underwent complete TA/TP repair at a median age of
      1.6 years (range 0.2 to 55.6 years). RESULTS: Follow-up (median 8.5 years, range
      0.5 to 14.6 years) was 100% completed. There was no operative death. There were
      three early re-operations: one for residual right ventricular outflow tract
      obstruction (RVOTO), one for intractable arrhythmias and one for remote second
      ventricular septal defect (VSD). There were three non-cardiac-related late
      deaths. Actuarial survival at 14 years was 98.8% (242/245). Twenty five patients
      required late re-operation, including 23 patients (9.4%, 23/245) who had
      pulmonary valve replacement (PVR). All other patients remained asymptomatic at
      follow-up. Mean residual right ventricular outflow tract (RVOT) pressure
      gradients have remained stable (6.8 +/- 6.6 mmHg, 95% CI 5.9-7.6, early
      postoperatively, versus 7.6 +/- 7.5 mmHg, 95% CI 6.6-8.6 at follow-up; P =
      0.015). The mean qualitative grade of pulmonary valve insufficiency (PVI)
      increased (from 1.4 +/- 0.9, 95% CI 1.3-1.5 at discharge to 2.1 +/- 1.2, 95% CI 2
      2.3 at follow-up; P < 0.001). Similarly, mean qualitative grade of tricuspid
      valve insufficiency (TVI) also increased (from 1 +/- 0.7, 95% CI 0.9-1 at
      discharge to 1.5 +/- 0.8, 95% CI 1.4-1.6 at follow-up; P < 0.001). However, RV
      function has remained normal in most patients. No significant arrhythmias have
      been noted. CONCLUSIONS: Our management strategy of non-neonatal TA/TP repair for
      all patients with TOF is associated with minimal early and late mortality and
      morbidity, relatively low re-operation rate, preserved RV function and excellent
      clinical outcomes at follow-up over almost 14 years. Since many patients
      demonstrated progressive increase in PVI and TVI, a much longer follow-up is
      necessary to determine the ultimate rates of late re-operation for pulmonary
      valve replacement (PVR).

PMID- 22627662
TI  - Bronchial artery aneurysms and bronchial artery-pulmonary artery fistula.

PMID- 22627663
TI  - David procedure during a reoperation for ongoing chronic Q fever infection of an
      ascending aortic prosthesis.
AB  - Chronic Q fever infections, caused by Coxiella burnetii, are associated with
      cardiovascular complications, mainly endocarditis and vascular (graft)
      infections. We report a case of a patient with a C. burnetii infected thoracic
      aorta graft treated initially in a conservative way. However, surgical excision
      of the infected graft was eventually necessary. This case report highlights the
      challenges regarding the treatment of patients with chronic vascular C. burnetii
      infections. In the absence of practical guidelines, treatment is tailored to the
      individual patient. Furthermore, we want to emphasize the need to include chronic
      Q fever in the differential diagnosis in patients with culture negative aortitis,
      especially in the regions with Q fever epidemics in the recent past.

PMID- 22627664
TI  - Right atrial thrombosis and pulmonary embolism after atrial septal defect repair:
      could it be hereditary thrombophilia?

PMID- 22627666
TI  - The Kunitz 1 and Kunitz 3 domains of tissue factor pathway inhibitor are required
      for efficient inhibition of factor Xa.
AB  - Tissue factor pathway inhibitor (TFPI) is a slow tight-binding inhibitor that
      inhibits factor (F)Xa in a biphasic fashion: a rapid formation of loose FXa.TFPI
      encounter complex is followed by slow rearrangement into a tight FXa.TFPI*
      complex in which the Kunitz-2 (K2) domain of TFPI binds and inhibits FXa. In the
      current study, full-length TFPI (TFPIfl) and various truncated TFPI constructs
      were used to assess the importance of TFPI domains other than K2 in the
      inhibition of FXa. In the absence of Ca2+ ions, FXa was more effectively
      inhibited by TFPIfl than Gla-domain less FXa. In turn, Ca2+ ions impaired FXa
      inhibition by TFPIfl but not by TFPI constructs that lack the C-terminus. This
      suggests that, in absence of Ca2+ ions, interactions between the C-terminus of
      TFPI and the Gla-domain of FXa promote FXa-inhibition. TFPIfl and K2K3 had
      similar efficiencies for encounter complex formation. However, K2K3 showed
      monophasic inhibition instead of biphasic inhibition, indicating absence of
      rearrangement into a tight complex. K1K2 and TFPI1-161 showed biphasic
      inhibition, but had less efficient encounter complex formation than TFPIfl.
      Finally, K2K3 was a 10-fold more efficient FXa- inhibitor than K2. These results
      indicate that K3-C-terminus enhances the formation of encounter complex and that
      K1 is required for isomerisation of the encounter- into tight complex. Since
      TFPIfl has a 10-fold higher Ki than K2K3-C-terminus, we propose that K1 is not
      only required for the transition of the loose to the tight FXa.TFPI* complex, but
      also inhibits FXa.TFPI encounter complex formation. This inhibitory activity is
      counteracted by K3 and C-terminus.

PMID- 22627667
TI  - A single application of low-energy radial extracorporeal shock wave therapy is
      effective for the management of chronic patellar tendinopathy.
AB  - PURPOSE: Extracorporeal shock wave therapy (SWT) is effective for the management
      of chronic recalcitrant tendinopathy. The objective of the current study was to
      assess whether a standardized, single treatment SWT is effective for the
      management of chronic patellar tendinopathy METHODS: Thirty-three patients with
      chronic patellar tendinopathy received low-energy SWT. Thirty-three patients with
      chronic patellar tendinopathy received other forms of non-operative therapy
      (control group). Evaluation was by change in Visual Analogue Scale (VAS),
      Victoria Institute of Sport Assessment score for patellar tendinopathy (VISA-P)
      score and by Roles and Maudsley Score. RESULTS: Mean pre-treatment VAS scores for
      the control and SWT groups were 7.5 and 7.8, respectively. One month, 3 months,
      and 12 months after treatment, the mean VAS for the control and SWT groups were
      6.7 and 4.3 (p < 0.001), 5.9 and 3.5 (p < 0.001), and 5.1 and 2.7 (p < 0.001),
      respectively. One month, 3 months, and 12 months after treatment, the mean VISA
      for the control and SWT groups were 50.7 and 65.5 (p < 0.001), 52.1 and 71 (p <
      0.001), and 54.9 and 74.5 (p < 0.001), respectively. At final follow-up, the
      number of excellent, good, fair, and poor results for the SWT and control groups
      were 8 and 3 (p < 0.001), 17 and 10 (p < 0.001), 5 and 16 (p < 0.001), and 3 and
      4 (p < 0.001), respectively. The percentage of patients with excellent ("1") or
      good ("2") Roles and Maudsley Scores (i.e. successful results) 12 months after
      treatment was statistically greater in the SWT group compared to the control
      group (p < 0.001). CONCLUSION: A single application of radial SWT is an effective
      treatment for chronic patellar tendinopathy. LEVEL OF EVIDENCE: III.

PMID- 22627668
TI  - Epistemology of psychiatry.
AB  - In historical and epistemological terms, psychiatry is a new discipline born
      during the 19th century. Rooted in both the natural and social sciences,
      psychiatric objects of inquiry, namely mental symptoms and mental disorders, are
      hybrid, constituted by the blending of components arising from disparate sources
      of knowledge ranging from the biological to the semantic in its widest sense.
      This poses problems for psychiatric research and therapy. Whilst conventional
      pluralism may be a convenient approach to manage aspects of psychiatric practice,
      it lacks the capacity to analyse psychiatric objects in their entirety. For the
      latter, psychiatry demands a new, tailored regional epistemology. This paper
      outlines the main features of an epistemology specific to the needs of
      psychiatry. It highlights the relational approach that needs to be taken and
      illustrates the usefulness of this approach by analysing the structure of
      psychiatric objects, exploring the manner in which they may be inscribed in the
      brain, and identifying the need to periodically recalibrate the language of
      psychiatry.

PMID- 22627669
TI  - A luminescent nanoscale metal-organic framework with controllable morphologies
      for spore detection.
AB  - A nanoscale MOF material NMOF 1 with controllable morphologies is realized whose
      morphology control has been simulated based on the BFDH method. The targeted NMOF
      1 exhibits highly sensitive, selective and instant "turn-on" sensing of bacterial
      endospores.

PMID- 22627670
TI  - Multifaceted tumor stromal fibroblasts.
AB  - Tumors are highly complex tissues composed of neoplastic cells and different
      kinds of stromal cells. Tumor stromal cells, especially fibroblasts, play
      important roles during the multistep development of tumors. In this review, the
      two-faced characteristics of tumor stromal fibroblasts are discussed in the light
      of our current knowledge. For one thing, fibroblasts act as an "inflammation
      regulator" by secretion of cytokines and regulation of tumor immunity; for
      another, they act as a "damage healer" for cure of wounds by remodeling
      extracellular matrix or taking a part in the "foreign body reaction". Since the
      properties of fibroblasts are complicated, both aspects of fibroblasts for tumor
      development should be considered carefully in clinical studies to target cancer
      associated fibroblasts.

PMID- 22627672
TI  - Blood and bones: osteoblastic HIF signaling regulates erythropoiesis.

PMID- 22627671
TI  - Attenuation of TORC1 signaling delays replicative and oncogenic RAS-induced
      senescence.
AB  - Numerous stimuli, including oncogenic signaling, DNA damage or eroded telomeres
      trigger proliferative arrest, termed cellular senescence. Accumulating evidence
      suggests that cellular senescence is a potent barrier to tumorigenesis in vivo,
      however oncogene induced senescence can also promote cellular transformation.
      Several oncogenes, whose overexpression results in cellular senescence, converge
      on the TOR (target of rapamycin) pathway. We therefore examined whether
      attenuation of TOR results in delay or reversal of cellular senescence. By using
      primary human fibroblasts undergoing either replicative or oncogenic RAS-induced
      senescence, we demonstrated that senescence can be delayed, and some aspects of
      senescence can be reversed by inhibition of TOR, using either the TOR inhibitor
      rapamycin or by depletion of TORC1 (TOR Complex 1). Depletion of TORC2 fails to
      affect the course of replicative or RAS-induced senescence. Overexpression of
      REDD1 (Regulated in DNA Damage Response and Development), a negative regulator of
      TORC1, delays the onset of replicative senescence. These results indicate that
      TORC1 is an integral component of the signaling pathway that mediates cellular
      senescence.

PMID- 22627673
TI  - Microvascular decompression for hemifacial spasm: technical notes on
      pontomedullary sulcus decompression.
AB  - BACKGROUND: Hemifacial spasm usually results from compression of facial nerve by
      offending vessels. During microvascular decompression, offending vessels at
      pontomedullary sulcus are obscured by the lower cranial nerve roots, making
      exposure and surgery difficult. This study discusses the techniques for
      decompression of offending vessels in this area. METHODS: Of 213 patients who
      underwent microvascular decompression for hemifacial spasm, 34 patients had
      compression of the facial nerve at the pontomedullary sulcus by offending
      vessels. Details of the intraoperative exposure and the arrangement of the lower
      cranial nerve roots are reviewed. The handling of the vertebral artery (VA) and
      the protection of perforating vessels is also discussed. RESULTS: Sixteen
      patients had the compact type of cranial nerve root arrangement, 13 had the loose
      type and five had the solitary type. Fifteen patients had compression by the VA.
      At 1 year after surgery, 30 patients had excellent results, two had good results
      and two had poor results. CONCLUSIONS: Microvascular decompression for hemifacial
      spasm can be performed with satisfying results if there is full exposure and
      protection of the perforating vessels, appropriate use of the spaces between
      cranial nerve roots, and attention paid to the characteristics of offending
      vessels.

PMID- 22627676
TI  - Islet microarchitecture and glucose transporter expression of the pancreas of the
      marmoset monkey display similarities to the human.
AB  - The common marmoset New World monkey (Callithrix jacchus), is a primate model
      with great potential for scientific research, including research on diabetes.
      However, in opposite to Rhesus and Java monkeys (Macaca mulatta and Macaca
      fascicularis) little is known about the marmosets islet microarchitecture,
      glucose transporter and pancreatic marker gene expression. In this work we
      analyze differences and similarities in size, shape, cellular composition and
      intra-islet topography between the common marmoset and the human endocrine
      pancreas. Different sized, circular and a-circular shaped islets of the common
      marmoset and human display alpha-cells in the whole islet organ leading to a
      ribbon-like islet type. The number of islets was significantly higher in the
      common marmoset compared with humans. However, the area of insulin-producing
      cells was significantly higher in the human pancreas. Intra-islet distribution
      pattern of delta- and beta-cells was similar in both species. The morphology of
      the exocrine pancreas regarding acinar and ductal cells was quite similar as
      confirmed by ultrastructural analysis. Additionally the ultrastructure of
      secretory granules from alpha-, delta- and beta-cells of human and non-human
      primate pancreas showed the same characteristics. Molecular analysis showed the
      presence of endocrine pancreatic marker genes like PMCA2, NCX1, SUR1, KIR6.2,
      MAFA, NGN3 and PDX1 also expressed in the human. For the first time we could show
      presence of Glut 5 and 9 transporters in addition to the low abundance
      transporter Glut2 and the highly expressed Glut1 glucose transporter. We propose
      that Callithrix jacchus displays a new animal model for diabetes research and
      regenerative medicine.

PMID- 22627677
TI  - Gender-specific effects of exercise on cardiac pathology in Na(+)/H(+) exchanger
      overexpressing mice.
AB  - The Na(+)/H(+) exchanger isoform 1 (NHE1) has been implicated in various cardiac
      pathologies including ischemia/reperfusion damage to the myocardium and cardiac
      hypertrophy. It is known that NHE1 levels increase in cardiac disease and we have
      recently demonstrated that expression of an activated NHE1 protein promotes
      cardiac hypertrophy in the mouse myocardium. We examined the gender-specific
      effects of exercise in combination with elevated cardiac expression of NHE1 on
      the myocardium in mice. Control mice and transgenic mice expressing elevated
      levels of wild type NHE1 and activated NHE1 were examined. There were gender
      specific differences in the effects of NHE1 with exercise. Exercised wild type
      male mice showed a tendency toward increased heart weight. This was not apparent
      in female mice expressing elevated NHE1 levels. In some transgenic female mice,
      there was a significant decrease in the size of the exercised hearts, which was
      different from what occurred with male mice. Body weight was maintained in
      exercised control and transgenic male mice; however, it decreased in female mice
      with exercise more so in transgenic female mice expressing elevated levels of
      NHE1. Female mice expressing activated NHE1 had elevated HW/BW ratios compared to
      males, and this was exaggerated by exercise. These results suggest that gender
      specific activation of NHE1 may be critical and that NHE1 plays a more critical
      role in promoting some types of hypertrophy in females in comparison with males.

PMID- 22627679
TI  - A better understanding of variation in cancer care.

PMID- 22627678
TI  - Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in
      younger newly diagnosed adult patients with acute myeloid leukemia.
AB  - This phase 1b trial investigated several doses and schedules of midostaurin in
      combination with daunorubicin and cytarabine induction and high-dose cytarabine
      post-remission therapy in newly diagnosed patients with acute myeloid leukemia
      (AML). The discontinuation rate on the 50-mg twice-daily dose schedule was lower
      than 100 mg twice daily, and no grade 3/4 nausea or vomiting was seen. The
      complete remission rate for the midostaurin 50-mg twice-daily dose schedule was
      80% (FMS-like tyrosine kinase 3 receptor (FLT3)-wild-type: 20 of 27 (74%), FLT3
      mutant: 12 of 13 (92%)). Overall survival (OS) probabilities of patients with
      FLT3-mutant AML at 1 and 2 years (0.85 and 0.62, respectively) were similar to
      the FLT3-wild-type population (0.78 and 0.52, respectively). Midostaurin in
      combination with standard chemotherapy demonstrated high complete response and OS
      rates in newly diagnosed younger adults with AML, and was generally well
      tolerated at 50 mg twice daily for 14 days. A phase III prospective trial is
      ongoing (CALGB 10603, NCT00651261).

PMID- 22627680
TI  - A clinically guided approach for improving performance measurement for
      hypertension.
AB  - BACKGROUND: Performance measures often fail to account for legitimate reasons why
      patients do not achieve recommended treatment targets. METHODS: We tested a novel
      performance measurement system for blood pressure (BP) control that was designed
      to mimic clinical reasoning. This clinically guided approach focuses on (1)
      exempting patients for whom tight BP control may not be appropriate or feasible
      and (2) assessing BP over time. Trained abstractors conducted structured chart
      reviews of 201 adults with hypertension in 2 VA health care systems. Results were
      compared with traditional methods of performance measurement. RESULTS: Among 201
      veterans, 183 (91%) were male, and the mean age was 71+/-11 years. Using the
      clinically guided approach, 61 patients (30%) were exempted from performance
      measurement. The most common reasons for exemption were inadequate opportunity to
      manage BP (35 patients, 17%) and the use of 4 or more antihypertensive
      medications (19 patients, 9%). Among patients eligible for performance
      measurement, there was little agreement on the presence of controlled versus
      uncontrolled BP when comparing the most recent BP (the traditional approach) with
      an integrated assessment of BP control (kappa 0.14). After accounting for
      clinically guided exemptions and methods of BP assessment, only 15 of 72 patients
      (21%) whose last BP was >=140/90 mm Hg were classified as problematic by the
      clinically guided approach. CONCLUSIONS: Many patients have legitimate reasons
      for not achieving tight BP control, and the methods used for BP assessment have
      marked effects on whether a patient is classified as having adequate or
      inadequate BP control.

PMID- 22627681
TI  - Nickel catalyzed alkylation of N-aromatic heterocycles with Grignard reagents
      through direct C-H bond functionalization.
AB  - A novel protocol for nickel-catalyzed direct sp(2) C-H bond alkylation of N
      aromatic heterocycles has been developed. This new reaction proceeded efficiently
      at room temperature using a Grignard reagent as the coupling partner. This
      approach provides new access to a variety of alkylated N-aromatic heterocycles
      which are potentially of great importance in medicinal chemistry.

PMID- 22627682
TI  - Involvement of diacylglycerol kinase gamma in modulation of iNOS synthesis in
      Golgi apparatus of vascular endothelial cells.
AB  - The aim of this study was to clarify the role of diacylglycerol kinase (DGK)gamma
      in vascular endothelial cells. The mRNA and protein expression of DGKgamma and
      inducible nitric oxide synthase (iNOS) in rat aortic endothelial cells (RAECs)
      were investigated using RT-PCR, immunocytochemical, and immunoblot analyses. In
      RAECs, immunoreactivity of DGKgamma was detected in the cytoplasm as a tubular or
      reticular structure. DGKgamma immunoreactivity colocalized with those for GM130
      and Golgin 97 but not with that for protein disulfide isomerase (PDI). In the
      presence of brefeldin A, DGKgamma immunoreactivity was markedly decreased and
      displayed an aggregation-like pattern. After treatment of RAECs with nocodazole,
      DGKgamma immunoreactivity was detected in Golgi stacks, which were severely
      segmented and appeared in vesicular shape. Stimulation with IL-1beta increased
      mRNA expression of DGKgamma, which was strongly attenuated by SB203580, a p38
      MAPK inhibitor. IL-1beta also induced expression of iNOS, which was observed as a
      tubular structure, and this distribution coincided with DGKgamma
      immunoreactivity. Brefeldin A reduced both iNOS immunoreactivity and DGKgamma
      immunoreactivity. iNOS expression was impaired by DGK inhibitors, R59022 and
      R59949. These results suggest that DGKgamma is upregulated by IL-1beta through
      the p38 MAPK pathway and may be involved in protein trafficking of iNOS in
      vascular endothelial cells.

PMID- 22627683
TI  - Depression and suicidal ideation in college students.
AB  - BACKGROUND/AIMS: Suicide is one of the leading causes of death in college
      students and is often associated with depression. The aim of this study was to
      assess the rates of suicidal ideation (SI) on college campuses and to identify
      its correlates. METHODS: On-campus depression screening sessions were conducted
      at 3 universities (n = 898; 55% female; mean age 20.07 +/- 1.85 years).
      Participants completed the Beck Depression Inventory (BDI; mean +/- SD of total
      score = 6.27 +/- 6.31) and other measures. Eighty-four students endorsed a '1' on
      the BDI suicidality item, suggesting thoughts of suicide. RESULTS: Results showed
      that students with greater depression severity, higher levels of hopelessness,
      and poorer quality of life were more likely to endorse SI. CONCLUSION: Factors
      associated with SI highlighted in this study may aid in the identification of
      college students at risk for suicide.

PMID- 22627684
TI  - Translational platelet research in patients with coronary artery disease: what
      are the major knowledge gaps?
AB  - Translational platelet function investigations performed in the percutaneous
      coronary intervention (PCI)-treated population receiving clopidogrel have
      identified high platelet reactivity to ADP (HPR) as a major risk factor for both
      acute as well as long-term ischaemic event occurrence, including stent
      thrombosis. Recent studies have highlighted the relation of single nucleotide
      polymorphisms of genes involved in clopidogrel absorption and metabolism to
      reduced pharmacokinetic and pharmacodynamic responses to clopidogrel.  CYP 2C19
      loss-of-function (LoF) allele  carriage has been associated with increased
      thrombotic risk in the PCI population. However, there is no information regarding
      the utility of platelet function testing to predict outcomes in patients with
      stable coronary artery disease and in medically managed patients with acute
      coronary syndromes. Additionally, few studies have included longitudinal
      assessment of platelet function to assess a potential time-dependent relation to
      ischaemic event occurrence and no phase-III antiplatelet-therapy trial has
      included a large enough platelet function sub-study to examine the relation
      between on-treatment platelet reactivity, bleeding, and ischaemic event
      occurrence. Therefore, futher studies are needed to delineate the role of
      platelet function testing across the spectrum of symptomatic coronary artery
      disease.

PMID- 22627685
TI  - It's a small world after all.

PMID- 22627686
TI  - Somatostatin analogs as a first-line treatment in acromegaly:  when is it
      appropriate?
AB  - PURPOSE OF REVIEW: To discuss the role of medical therapy of acromegaly as a
      first-line treatment, focusing on recent data on the use of somatostatin analogs
      (SSAs), the first-choice pharmacotherapy for treating acromegaly. RECENT
      FINDINGS: Despite pituitary surgery and radiotherapy, a significant number of
      patients with acromegaly needed adjuvant medical therapy, and primary medical
      therapy nowadays is increasingly considered. According to a recent consensus
      statement on the management of acromegaly, primary pharmacological therapy with
      SSAs may be indicated in patients who are otherwise poor surgical candidates or
      refuse surgery, and in those in whom there is a low probability of a surgical
      cure. The long-acting SSAs have been found to be effective in improving symptoms
      and signs of acromegaly in a high percentage of patients and induce normalization
      of growth hormone and insulin-like growth factor-I levels approximately in 60-80%
      of patients, respectively. Evidence has suggested that SSAs induce a clinically
      significant tumor shrinkage when given as first-line, when this reduction of
      tumor volume could be helpful in improving the outcome of subsequent surgery or
      improving the clinical syndrome in patients with unacceptable surgical risk,
      whereas the tumor shrinkage was seen less frequently when the drug was used after
      surgical resection and/or radiotherapy. SUMMARY: Pharmacological management plays
      a pivotal role in the treatment of acromegaly, and first-line medical therapy
      with SSAs is being widely used in clinical practice, either prior to surgery or
      in patients who are otherwise poor surgical candidates and in those in whom there
      is a low probability of a surgical cure.

PMID- 22627687
TI  - Measuring treatment motivation in secure juvenile facilities.
AB  - The present study examined the validity and reliability of the Adolescent
      Treatment Motivation Questionnaire (ATMQ) in a sample of 264 adolescents in Dutch
      secure juvenile facilities. Confirmatory factor analysis of a single-factor model
      of "treatment motivation" showed a close fit to the data, indicating construct
      validity of the ATMQ. Concurrent validity was supported by significant relations
      between treatment motivation and living group climate. Internal consistency
      reliability in terms of Cronbach's alpha was good (.84). The ATMQ proved to be
      insensitive to the tendency to provide socially acceptable or desirable answers,
      which supports discriminant validity, and was unrelated to sex, age, and self
      reported aggression of the adolescents. The ATMQ is a parsimonious instrument (11
      items) enabling future research on treatment motivation in secure juvenile
      facilities. 

PMID- 22627688
TI  - The role of trait anxiety in reducing the relationship between childhood exposure
      to violence/victimization and subsequent violent behavior among male delinquent
      youth.
AB  - In this project, the authors examined the relationship trait anxiety has on
      incarcerated male adolescents' progression from childhood exposure to
      violence/victimization to violent behavior. Self-report survey data were analyzed
      to determine the youth's levels of trait anxiety, how the degree of childhood
      trauma was related to their level of anxiety, as well as whether their level of
      anxiety affected the relationship between trauma and subsequent frequency and
      severity of their delinquent acts using a moderation analysis. Anxiety
      significantly decreased the relationship between victimization and the commission
      of violence (F = 15.93, p < .001). 

PMID- 22627696
TI  - Reduced steady state-based peripheral blood stem cell harvest rate in multiple
      myeloma treated with bortezomib-based induction regimens.

PMID- 22627695
TI  - Folate and Alzheimer: when time matters.
AB  - Folate is necessary for DNA and mtDNA integrity and via folate/B12-dependent
      methionine cycle for methylation of multiple substrates (epigenetic DNA and
      enzymes) and methylation of homocysteine. During embryogenesis, folate deficiency
      is a risk factor for neural tube defects and late in life for cognitive decline
      and Alzheimer's dementia (AD). It induces several Alzheimer pathomechanisms like
      oxidative stress, Ca(++) influx, accumulation of hyperphosphorylated tau and beta
      amyloid. But impact of folic acid supplementation on prevention or delay of
      dementia is a matter of debate. Six out of seven randomized controlled trials
      (RCT) with B vitamin intervention periods between 2 and 5.4 years reported about
      cognitive benefits in the supplemented groups mainly for those subjects with high
      homocysteine or low folate levels at baseline. This review tries to demonstrate
      the connection between folate deficiency and AD, analyses selected epidemiologic
      studies and RCT on folate/B12/homocysteine with long-observation periods (>= 2
      years RCT; >= 4 years observational) and attempts to find explanations for the
      controversy in literature like short follow-up, heterogeneity of subjects
      concerning age, recruitment, baseline cognition, inclusion criteria and probably
      "misleading"(not representative for the past) folate/B12/homocysteine levels due
      to not reported short-term use of multivitamins or food-fortification. Population
      based studies-epidemiologic and interventional-starting in the fourth decade
      would provide the best information about the impact of folate on later
      development of AD. Mandatory folate fortification areas will be important future
      field studies for-like neural tube defects-hopefully declining AD incidence and
      disproving safety concerns.

PMID- 22627697
TI  - Workshop on programming beta cell development, impairment and regeneration.
AB  - Helsingor, the city of Hamlet in Denmark, provided the site for the workshop
      "Programming Beta Cell Development, Impairment and Regeneration" on October 23
      26th, 2011. The same location has held two EASD Islet study group meetings, while
      the previous three workshops were held in Helsinki, Finland (2003), El Perello,
      Spain (2006) and Peebles, Scotland (2009). The meeting drew 190 attendees from 12
      different countries. There were 37 main oral presentations, and 68 posters
      covered virtually all aspects of the pancreas and provided a dynamic snapshot of
      the most interesting areas of current investigation. In addition, six parallel
      workshops on stem cells, epigenetics, autoimmunity, beta-cell imaging, beta-cell
      identity, omics in beta-cell research and a panel discussion on "to be or not to
      be a beta cell" were held. Here, we will review some of the newest highlights and
      still unanswered questions in the field.

PMID- 22627698
TI  - Extracting biological information with computational analysis of Fourier
      transform infrared (FTIR) biospectroscopy datasets: current practices to future
      perspectives.
AB  - Applying Fourier-transform infrared (FTIR) spectroscopy (or related technologies
      such as Raman spectroscopy) to biological questions (defined as biospectroscopy)
      is relatively novel. Potential fields of application include cytological,
      histological and microbial studies. This potentially provides a rapid and non
      destructive approach to clinical diagnosis. Its increase in application is
      primarily a consequence of developing instrumentation along with computational
      techniques. In the coming decades, biospectroscopy is likely to become a common
      tool in the screening or diagnostic laboratory, or even in the general
      practitioner's clinic. Despite many advances in the biological application of
      FTIR spectroscopy, there remain challenges in sample preparation, instrumentation
      and data handling. We focus on the latter, where we identify in the reviewed
      literature, the existence of four main study goals: Pattern Finding; Biomarker
      Identification; Imaging; and, Diagnosis. These can be grouped into two
      frameworks: Exploratory; and, Diagnostic. Existing techniques in Quality Control,
      Pre-processing, Feature Extraction, Clustering, and Classification are critically
      reviewed. An aspect that is often visited is that of method choice. Based on the
      state-of-art, we claim that in the near future research should be focused on the
      challenges of dataset standardization; building information systems; development
      and validation of data analysis tools; and, technology transfer. A diagnostic
      case study using a real-world dataset is presented as an illustration. Many of
      the methods presented in this review are Machine Learning and Statistical
      techniques that are extendable to other forms of computer-based biomedical
      analysis, including mass spectrometry and magnetic resonance.

PMID- 22627700
TI  - Derlin-1-immunopositive inclusions in patients with Alzheimer's disease.
AB  - Amyloid plaques and neurofibrillary tangles are the major pathological hallmarks
      of Alzheimer's disease. Neurofibrillary tangles are composed of filaments and
      paired helical filaments containing polymerized hyperphosphorylated tau protein.
      Derlin proteins are a family of proteins that are conserved in all eukaryotes, in
      which they function in endoplasmic reticulum-associated degradation. Protein
      disulfide isomerase (PDI) is a member of the thioredoxin superfamily and is
      believed to accelerate the folding of disulfide-bonded proteins in the luminal
      space of the endoplasmic reticulum. In this study, we found that derlin-1 and PDI
      were colocalized in neurofibrillary tangles in the brain of patients with
      Alzheimer's disease. Derlin-1 and PDI may work as partners to avoid the
      accumulation of unfolded proteins in Alzheimer's disease. Furthermore, we found
      that derlin-1 was immunopositive for neurofibrillary tangles and upregulated in
      Alzheimer's disease and that derlin-1 may play an important role in endoplasmic
      reticulum-associated degradation during the pathogenesis of Alzheimer's disease.
      We hypothesize that derlin-1 was upregulated to avoid the aggregation of unfolded
      proteins. Despite the upregulation of derlin-1, the functions of chaperone
      proteins and Alzheimer tau protein were lost and these proteins were also
      accumulated. Finally, they were involved in neurofibrillary tangles. These
      results suggest that derlin-1 may be associated with endoplasmic reticulum stress
      in neuronal cells in Alzheimer's disease.

PMID- 22627699
TI  - Negative regulation of human astrocytes by interferon (IFN) alpha in relation to
      growth inhibition and impaired glucose utilization.
AB  - The present study assessed the direct effects of IFNs on human astrocytes. Human
      astrocytes were exposed to human recombinant IFNs, and the proliferation of cells
      was measured. Type I IFN receptor mRNA and protein expression, the phosphoprotein
      levels of signaling molecules including JNK, ERK1/2, IkappaB, p38MAPK, Stat3, and
      the expression of cytokines were determined respectively. In addition, cellular
      glucose consumption was measured as well as Glut-1 protein and activation of GSK
      3beta/mTOR signal were determined. The expression of Type I IFN receptor was
      detected in cultured human astrocytes. 2 IU/ml IFNalpha2a and IFNalpha2b
      significantly decreased the proliferation of human astrocytes respectively,
      compared to control. IFNbeta had no significant effect on the proliferation of
      the cells. The phosphorylation of JNK stimulated by all IFNs detected was more
      pronounced and sustained than ERK1/2 and IkappaB. No effects were observed on the
      activation of p38MAPK and Stat3. Moreover, Treatment with IFNalpha, especially
      with IFNalpha2b, decreased glucose consumption and stimulated phosphorylation of
      GSK-3beta and mTOR, but decreased the expression of Glut-1. In contrast, IFNbeta
      had no significant effect on either glucose consumption or activation of GSK
      3beta/mTOR signals. INFalpha2b significantly decreased the levels of IL-8 whereas
      the levels of GM-CSF were increased. The present study demonstrates direct
      inhibitory effects of IFNalpha on cell proliferation, cell signaling and glucose
      utilization in human astrocytes.

PMID- 22627701
TI  - Covalent attachment of antagonists to the alpha7 nicotinic acetylcholine
      receptor: synthesis and reactivity of substituted maleimides.
AB  - The 3-methylmaleimide congeners of the natural product methyllycaconitine (MLA)
      and an analogue covalently attach to functional cysteine mutants of the alpha7
      nicotinic acetylcholine receptor (nAChR).

PMID- 22627702
TI  - Insight and awareness as related to psychopathology and cognition.
AB  - BACKGROUND: Insight affects adherence and treatment outcome and relates to
      cognitive impairment and psychopathology. We investigated the relationship of
      insight with cognition in patients with major depression, schizophrenia and
      bipolar disorder in acute psychiatric care, long-term inpatient, and outpatient
      settings. METHODS: Eighty-one patients (women, 59.5%; age, 45.9 +/- 13.5 years;
      27 in each setting group; 33.3% with DSM-IV bipolar disorder, 39.5% with unipolar
      major depression, and 27.2% with schizophrenia) underwent the Wisconsin Card
      Sorting Test (WCST) to test flexibility, clinician-rated Scale to Assess
      Unawareness of Mental Disorder (SUMD), and self-rated Insight Scale (IS) to
      assess insight/awareness. RESULTS: Poor performance on the WCST correlated with
      higher SUMD scores such as current psychiatric illness unawareness, impaired
      symptom attribution, unawareness of medication effect, or of social consequences,
      but not with IS scores. The latter correlated with days on continuous treatment.
      Patients receiving psycho-education showed greater symptom awareness compared to
      patients treated with drugs alone. Cognitive flexibility and diagnostic category
      did not correlate. Poor insight corresponded with severe mental illness,
      particularly acute psychosis. CONCLUSIONS: Treatment setting specificity reflects
      psychopathology and severity. Insight is inversely proportional to illness
      severity and cognitive flexibility, which is also affected by psychopathology.
      Limitations comprise group heterogeneity, cross-sectional design, and limited
      sample size.

PMID- 22627703
TI  - Liposomal glyco-microarray for studying glycolipid-protein interactions.
AB  - A microarray enables high-throughput interaction screening of numerous
      biomolecules; however, fabrication of a microarray composed of cellular membrane
      components has proven difficult. We report fabrication of a liposomal glyco
      microarray by using an azide-reactive liposome that carries synthetic and natural
      glycolipids via chemically selective and biocompatible liposome immobilization
      chemistry. Briefly, liposomes carrying anchor lipid
      dipalmitoylphosphatidylethanolamine (DPPE)-PEG(2000)-triphenylphosphine and
      ganglioside (GM1 or GM3) were prepared first and were then printed onto an azide
      modified glass slide so as to afford a liposomal glyco-microarray via Staudinger
      ligation. Fluorescent dye release kinetics and fluorescence imaging confirmed
      successful liposome immobilization and specific protein binding to the intact
      arrayed glycoliposomes. The liposomal glyco-microarray with different
      gangliosides showed their specific lectin and toxin binding with different
      binding affinity. The azide-reactive liposome provides a facile strategy for
      fabrication of either a natural or a synthetic glycolipid-based membrane-mimetic
      glycoarray. This liposomal glyco-microarray is simple and broadly applicable and
      thus will find important biomedical applications, such as studying glycolipid
      protein interactions and toxin screening applications.

PMID- 22627704
TI  - Multi-elemental bio-imaging of rat tissue from a study investigating the
      bioavailability of bismuth from shotgun pellets.
AB  - In recent years, bismuth has been promoted as a "green element" and is used as a
      substitute for the toxic lead in ammunition and other applications. However, the
      bioavailability and toxicity of bismuth is still not very well described.
      Following a hunting accident with bismuth-containing shots, a bioavailability
      study of bismuth from metal pellets inoculated into rat limb muscles was carried
      out. Bismuth could be found in urine and blood of the animals. Bio-imaging using
      laser ablation ICP-MS of thin sections of the tissue around the metal implant was
      carried out to find out more about the distribution of the metal diffusing into
      the tissue. Two laser ablation systems with different ablation cell designs were
      compared regarding their analytical performance. Low concentrations of bismuth
      showing a non-symmetrical pattern were detected in the tissue surrounding the
      metal implant. This was partly an artefact from cutting the thin sections but
      also bio-mobilisation of the metals of the implant could be seen. An accumulation
      of zinc around the implant was interpreted as a marker of inflammation.
      Challenges regarding sample preparation for laser ablation and bio-imaging of
      samples of diverse composition became apparent during the analysis.

PMID- 22627705
TI  - The impact of intense airway management training on paramedic knowledge and
      confidence measured before, immediately after and at 6 and 12 months after
      training.
AB  - INTRODUCTION: Airway management is a core component in the practice of advanced
      life support (ALS) paramedics. OBJECTIVE: To determine if an intense airway
      management course would improve ALS paramedic knowledge and confidence and if
      knowledge was retained over time. METHODS: An identical written survey (measuring
      demographics and confidence) and multiple-choice examination (measuring
      knowledge) was administered at the start and end of a 10 h airway course. At 6
      and 12 months after the course, paramedics took the knowledge examination. Paired
      confidence and written knowledge examination scores before and immediately after
      the course were compared. Differences between knowledge examination scores at all
      four time points (before, immediately after and at 6 and 12 months) were tested
      using analysis of variance and Tukey's test. RESULTS: 299 ALS paramedics were
      enrolled in the study. 209 (69%) reported 6 or more years of ALS experience. The
      mean pre-course confidence score was 2.74/4 and the mean post-course confidence
      score was 3.39/4; a difference of 0.7 points (95% CI 0.61 to 0.71). Post-course
      examination scores improved by 4.9 points (95% CI 4.58 to 5.20), from 7.7 to
      12.6/20. At 6 months the mean score was 10.3/20, and at 12 months 10.2/20. Post
      course scores were significantly better than pre-course scores. Scores at 6 and
      12 months did not differ significantly and remained significantly improved from
      pre-course scores. CONCLUSION: Significant improvement in confidence and
      knowledge was found after paramedics completed an intense airway management
      course. Knowledge at 6 and 12 months remained significantly better compared with
      pre-course.

PMID- 22627706
TI  - Is lidocaine Bier's block safe?
AB  - OBJECTIVES: To assess the safety profile of lidocaine Bier's block when compared
      with that of prilocaine. METHOD: A retrospective audit of patients undergoing
      Bier's block using 0.5% lidocaine during a 27-month period (April 2008-June 2010)
      at the Royal United Hospital Bath emergency department. RESULTS: 416 patients
      with sufficient data were included in the study; 360 women and 56 men. The mean
      patient age was 65 years. Complications were reported in 39 cases; transient
      hypotension/vasovagal episodes and transient mild bradycardia were most frequent.
      No patients required any medical intervention. There was no occurrence of
      anaphylaxis, convulsion, hypotensive episodes requiring medical intervention,
      collapse or death. CONCLUSION: No clinically significant morbidity or mortality
      as a consequence of lidocaine Bier's block was demonstrated in this audit.

PMID- 22627707
TI  - Acupuncture stimulation at HT7 alleviates depression-induced behavioral changes
      via regulation of the serotonin system in the prefrontal cortex of maternally
      separated rat pups.
AB  - A possible application of acupuncture in alleviating depression-like behavioral
      changes and regulating serotonin signaling in the prefrontal cortex (PFC) of
      maternally-separated rat pups was investigated in this study. On postnatal day
      15, rat pups were maternally-separated and received acupuncture stimulation at
      acupoint HT7 or ST36 once a day for 7 days. On postnatal day 21, the tail
      suspension test was performed and the PFC was harvested. Tissue levels of
      serotonin (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) were then measured by
      high-performance liquid chromatography and expression of serotonin transporter (5
      HTT) and brain-derived neurotrophic factor (BDNF) were assessed by western
      blotting. Levels of 5-HT and 5-HIAA were not significantly changed, but the 5
      HIAA/5-HT ratio was significantly increased by maternal separation. The
      immobility time of maternally-separated rat pups was increased, and increased 5
      HTT expression and reduced BDNF level were observed in the PFC. But acupuncture
      stimulation at HT7 alleviated the behavioral change and regulated the changes of
      5-HIAA/5-HT ratio, 5-HTT, and BDNF. In conclusion, acupuncture stimulation at HT7
      can relieve maternal separation-induced changes, and we propose that regulation
      of the 5-HIAA/5-HT ratio and of 5-HTT expression by acupuncture stimulation are
      important acupuncture-induced benefits in this animal model of depression.

PMID- 22627709
TI  - Small and large PROS1 deletions but no other types of rearrangements detected in
      patients with protein S deficiency.
AB  - Protein S deficiency is a dominantly inherited disorder that results from
      mutations in the  PROS1  gene. Previous sequencing of the gene failed to detect
      mutations in eight out of 18 investigated Swedish families, whereas segregation
      analyses detected large deletions in three out of the eight families. The present
      study investigates more thoroughly for the presence of deletions but also for
      other types of rearrangements. FISH analysis confirmed the existence of the three
      previously identified large deletions, but failed to identify any other type of
      rearrangement among the eight analysed families. MLPA analysis of the  PROS1 
      gene revealed two smaller deletions covering two and four exons, respectively.
      Thus, deletions could be found in five out of eight families where no point
      mutations could be found despite sequencing of the gene. Twelve additional, not
      previously analysed, families were subsequently analysed using MLPA. The analysis
      identified two smaller deletions (3 and 4 exons). Including all PS-deficient
      families, i.e. also the 10 families where sequencing found a causative point
      mutation, deletions were identified in seven out of 30 PS-deficient families. A
      strategy of sequencing followed by MLPA analysis in mutation-negative families
      identified the causative mutation in 15 out of 18 of Swedish PS-deficient
      families. Most deletions were different as determined by their sizes, locations
      and flanking haplotypes. FISH (8 families) and MLPA analysis (20 families) failed
      to identify other types of rearrangements.

PMID- 22627708
TI  - Endochondral bone growth, bone calcium accretion, and bone mineral density: how
      are they related?
AB  - Endochondral bone growth in young growing mammals or adult mammals with
      persistent growth plates progresses from proliferation, maturation and
      hypertrophy of growth plate chondrocytes to mineralization of cartilaginous
      matrix to form an osseous tissue. This complex process is tightly regulated by a
      number of factors with different impacts, such as genetics, endocrine/paracrine
      factors [e.g., PTHrP, 1,25(OH)(2)D(3), IGF-1, FGFs, and prolactin], and
      nutritional status (e.g., dietary calcium and vitamin D). Despite a strong link
      between growth plate function and elongation of the long bone, little is known
      whether endochondral bone growth indeed determines bone calcium accretion, bone
      mineral density (BMD), and/or peak bone mass. Since the process ends with
      cartilaginous matrix calcification, an increase in endochondral bone growth
      typically leads to more calcium accretion in the primary spongiosa and thus
      higher BMD. However, in lactating rats with enhanced trabecular bone resorption,
      bone elongation is inversely correlated with BMD. Although BMD can be increased
      by factors that enhance endochondral bone growth, the endochondral bone growth
      itself is unlikely to be an important determinant of peak bone mass since it is
      strongly determined by genetics. Therefore, endochondral bone growth and bone
      elongation are associated with calcium accretion only in a particular subregion
      of the long bone, but do not necessarily predict BMD and peak bone mass.

PMID- 22627710
TI  - Low dead-space syringes for preventing HIV among people who inject drugs: 
      promise and barriers.
AB  - PURPOSE OF REVIEW: This review examines evidence regarding the differential
      effects of high dead-space syringes (HDSS) and low dead-space syringes (LDSS) on
      HIV transmission among people who inject drugs (PWID). It also identifies areas
      for additional research and examines potential barriers to interventions that
      promote LDSS. RECENT FINDINGS: Results of laboratory experiments and cross
      sectional bio-behavioral surveys provide circumstantial evidence that the
      probability of HIV transmission associated with sharing LDSS is less than the
      probability of HIV transmission associated with sharing HDSS. Mathematical models
      suggest that LDSS may prevent injection-related HIV epidemics among PWID.
      SUMMARY: Circumstantial evidence suggests that LDSS may substantially reduce HIV
      transmission among PWID, who share syringes. Additional research that links LDSS
      to reductions in HIV incidence is needed. Most currently available LDSS are 1 ml
      or smaller and have fixed needles. These cannot be used by PWID 'injecting'
      larger volumes of fluid and they may be rejected by PWID, who prefer syringes
      with detachable needles. Nonetheless, LDSS represent a potentially promising
      intervention that deserves serious consideration.

PMID- 22627711
TI  - Pharmacovigilance and global HIV/AIDS.
AB  - PURPOSE OF REVIEW: This review focuses on current status, progress, challenges
      and opportunities in global pharmacovigilance for HIV/AIDS treatment. RECENT
      FINDINGS: Over 6 million HIV-infected individuals worldwide are on treatment with
      more than 150 innovator and generic antiretroviral drug products. This
      achievement is made possible through sponsorship of HIV/AIDS programs [The Global
      Fund to Fight AIDS, Tuberculosis and Malaria; the President's Emergency Program
      for AIDS Relief (PEPFAR)] and the availability of generic fixed-dose combination
      products. The WHO prequalifies generic drug products used by Global Fund
      programs; the US Food and Drug Administration tentatively approves generic
      products used by PEPFAR programs through a fast-track review process. Adequate
      national or regional quality and safety monitoring systems after drug
      distribution are lacking. The pharmaceutical sector, a significant player in
      pharmacovigilance in the developed world, has not been engaged. Innovative
      approaches based on collaboration and partnerships will be needed. Clinic-based
      or program-based cohort studies, randomized clinical trials and electronic
      medical records may contribute pharmacovigilance-relevant information. SUMMARY:
      Attention to drug quality and safety is obligatory for long-term program
      sustainability. Systematic approaches to regional pharmacovigilance that make use
      of diverse data sources, and collaborative partnerships between industry,
      clinical and/or research programs and national health authorities can potentially
      contribute to overall health system strengthening.

PMID- 22627712
TI  - Writing on the margins.

PMID- 22627713
TI  - The honesty effect.

PMID- 22627714
TI  - Authority figures.

PMID- 22627715
TI  - What's in a number?

PMID- 22627716
TI  - The influenza controversy: should limits be placed on science?

PMID- 22627717
TI  - Whither the Affordable Care Act?

PMID- 22627718
TI  - Exploring the limits of autonomy.

PMID- 22627719
TI  - The organ-that-must-not-be-named: female genitals and generalized references.

PMID- 22627720
TI  - Neuroscience and morality.

PMID- 22627721
TI  - Clinical use of placebos: still the physician's prerogative?
AB  - The American Medical Association's Code of Ethics holds that if a physician
      believes a treatment to be a placebo, then the patient should be informed of that
      belief, and the treatment should not be prescribed unless the patient agrees to
      its use. But this is not clearly the best way either to protect patients or to
      benefit them. The physician's own beliefs should not be decisive.

PMID- 22627722
TI  - The woman question in medicine: an update.
AB  - The women's movement rose to prominence decades ago, but women continue to be
      discriminated against in their encounters with medicine, as both patients and
      practitioners. How should bioethics think about this state of affairs?

PMID- 22627726
TI  - Role of oral cyclophosphamide in the treatment of giant cell arteritis.
AB  - OBJECTIVE: Glucocorticoid (GC)-related adverse events greatly contribute to the
      outcome in giant cell arteritis (GCA). CYC was investigated as a steroid-sparing
      agent in GCA. METHODS: Nineteen patients treated with CYC were retrospectively
      analysed. CYC was administered in 15 of the 19 patients after failure of high
      doses of GC or relapse during medium to high doses of GC, with or without MTX,
      while CYC was used ab initio in 4 of the 19 patients, all with type 2 diabetes.
      Follow-up ranged from 1 month to nearly 9 years after the end of CYC treatment.
      RESULTS: The efficacy of CYC was observed in 15 of the 19 patients, and remission
      was still present 6-12 months after CYC suspension in 12 of the 13 patients. GCs
      were suspended in 6 of the 15 patients, and they were continued at a dose <=5
      mg/day of prednisone in all the remaining responders. Relapse occurred in 4 of
      the 15 patients, usually >12 months after CYC suspension. Suspension of GC daily
      dose or reduction to <=5 mg/day of prednisone occurred within the first 6 months
      of follow-up after the beginning of CYC in 10 of the 15 patients. Ten adverse
      events were registered in nine patients, with recovery usually soon after the
      suspension of CYC or dose reduction. However, one death occurred due to acute
      hepatitis. Disappearance of the inflammatory infiltrate could be demonstrated
      when temporal artery biopsy was repeated 3 months after CYC in one patient.
      CONCLUSION: CYC may represent a useful option for patients requiring prolonged
      medium- to high-dose GC therapy and at high risk of GC-related side effects.

PMID- 22627727
TI  - Granulomatosis with polyangiitis involves sustained mucosal inflammation that is
      rich in B-cell survival factors and autoantigen.
AB  - OBJECTIVE: Granulomatosis with polyangiitis (GPA) is a rare chronic autoimmune
      disease that may be triggered by upper airway infection. ANCAs specific for PR3
      that is expressed by activated neutrophils and macrophages are associated with
      GPA. Our aim was to investigate regional immune mechanisms that might induce or
      support the autoimmune response in GPA. METHODS: Biopsy samples from 77 patients
      including 8 with GPA were studied by immunohistochemistry. B-cell homing subsets
      in blood samples from 16 patients with GPA and 11 healthy controls were studied
      by FACS. The distribution of B-cell clones was searched in paired biopsies and
      blood samples from one patient by analysing immunoglobulin heavy chain gene (IGH)
      junctional sequences. RESULTS: Activated B cells were located alongside PR3
      expressing cells and B-cell survival factors BAFF and APRIL in mucosa from
      patients with GPA. We detected APRIL production by the granulomas and giant
      cells. B cells were proliferating in all cases and persistent for 5 years in
      biopsies obtained from one patient. However, there was no evidence of B-cell
      clones from the mucosal biopsies circulating in peripheral blood in GPA or any
      numerical or proportional change in B-cell subsets expressing markers of regional
      homing in blood in GPA. CONCLUSIONS: Our study illustrates chronically activated
      B cells alongside autoantigens and B-cell survival factors in the mucosa in GPA.

PMID- 22627728
TI  - Reliability testing of tendon disease using two different scanning methods in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: To assess the intra- and interobserver reliability of musculoskeletal
      ultrasonography (US) in detecting inflammatory and destructive tendon
      abnormalities in patients with RA using two different scanning methods. METHODS:
      Thirteen observers examined nine patients with RA and one healthy individual in
      two rounds independently and blindly of each other. Each round consisted of two
      consecutive examinations, an anatomy-based examination and a free examination
      according to personal preferences. The following tendons were evaluated: wrist
      extensor compartments 2, 4 and 6, finger flexor tendons 3 and 4 at MCP level,
      tibialis posterior tendon and both peronei tendons. Overall, positive and
      negative agreements and kappa-values for greyscale (GS) tenosynovitis,
      peritendinous power Doppler (PPD) signal, intratendinous power Doppler (IPD)
      signal and GS tendon damage were calculated. RESULTS: Intraobserver kappa-value
      ranges were 0.53-0.55 (P < 0.0005) for GS tenosynovitis, 0.61-0.64 (P < 0.0005)
      for PPD signal, 0.65-0.66 (P < 0.0005) for IPD signal and 0.44-0.53 (P < 0.0005)
      for GS tendon damage. For interobserver reliability, substantial overall
      agreement ranged from 80 to 89% for GS tenosynovitis, 97 to 100% for PPD signal,
      97 to 100% for IPD signal and 97 to 100% for GS tendon damage. Results were
      independent of scanning technique. CONCLUSION: Intraobserver reliability for
      tenosynovitis and tendon damage varied from moderate for GS to good for PD.
      Overall interobserver reliability for tenosynovitis and tendon damage was
      excellent both for GS and PD. This qualitative scoring system may serve as the
      first step to a semi-quantitative score for tendon pathology.

PMID- 22627729
TI  - The epidemiology of rheumatoid arthritis in Kinshasa, Democratic Republic of
      Congo--a population-based study.
AB  - OBJECTIVE: To determine the prevalence of RA and its distribution among
      linguistic groups in the urban area of Kinshasa. METHODS: Investigators
      questioned all individuals living in randomly chosen streets in five randomly
      chosen health areas in Kinshasa. Age, sex, linguistic group and rheumatic
      complaints were noted. RA diagnosis by 1987 ACR classification criteria was
      checked in all suspect cases. Disease activity (DAS-28), functionality (HAQ), X
      ray damage, ACPA and RF positivity were assessed in patients confirmed with RA.
      RESULTS: A total of 5000 individuals were questioned, with 2700 females and 2300
      males [average age 25.7 (1.8) years]. Linguistic group definitions were obtained
      in 4587 subjects: 44.3% had Kongo roots, 16.9% Ngala, 16.7% Luba, 11% Swahili,
      3.6% Tetela and 7.6% miscellaneous. Thirty persons (age +/- 53 years) fulfilled
      the ACR criteria with a female/male sex ratio of 5. Mean age at disease onset was
      47.7 years. Kongo people had the highest RA prevalence (1%). Mean DAS-28 was 6.5,
      mean HAQ was 1.3. One-third of patients were RF and ACPA positive and had
      classical X-ray findings. CONCLUSION: The prevalence of RA in Kinshasa is 0.6 and
      0.9% in people aged >18 years. Disease activity was high, but RF and ACPA
      positivity was not frequent. The Kongo seems to be the most affected linguistic
      group.

PMID- 22627738
TI  - Convergence of dip-pen nanolithography and acoustic biosensors towards a rapid
      analysis multi-sample microsystem.
AB  - The present work demonstrates for the first time patterning of a ready-to-use
      biosensor with several different biomolecules using Dip-Pen Nanolithography (DPN)
      for the development of a procedure towards more rapid and efficient multi-sample
      detection. The biosensor platform used is based on a Surface Acoustic Wave (SAW)
      device integrated with a parallel-channel microfluidic module, termed as
      "microfluidics-on-SAW" ("MUF-on-SAW"), for reproducible multi-sample analysis.
      Lipids with different functionalized head groups were patterned at distinct,
      microfluidic-formed rectangular domains with sharp edges all located on the same
      sensor surface; pattern quality was verified using a fluorescent microscope. The
      functionality of the head groups, the efficiency of the patterning method, and
      the suitability of DPN for the surface modification of the acoustic device were
      subsequently examined through acoustic experiments. The MUF-on-SAW configuration
      was used to detect specific binding between the pre-patterned functionalized
      lipids with their corresponding biomolecules. The achievement of an improved
      sensitivity (5-fold compared to previous acoustic configurations) and reduced
      preparation time by at least 2 h clearly indicates the suitability of DPN as a
      direct patterning method for ready-to-use acoustic sensor devices like the MUF-on
      SAW towards integrated, rapid-analysis, multi-sample biosensing microsystem
      development.

PMID- 22627736
TI  - Involvement of actin filament in the generation of Ca2+ mobilizing messengers in
      glucose-induced Ca2+ signaling in pancreatic beta-cells.
AB  - Glucose is a metabolic regulator of insulin secretion from pancreatic beta-cells,
      which is regulated by intracellular Ca(2+) signaling. We and others previously
      demonstrated that glucose activates CD38/ADP-ribosyl cyclase (ADPR-cyclase) to
      produce two Ca(2+) second messengers, cyclic ADP-ribose (cADPR) and nicotinic
      acid adenine dinucleotide phosphate (NAADP). Although F-actin remodeling is known
      to be an important step in glucose stimulated insulin secretion, the role of
      actin cytoskeleton in regulating Ca(2+) signaling in pancreatic beta-cells remain
      to be solved. Here, we show that actin filaments are involved in the activation
      of CD38/ADPR-cyclase in pancreatic beta-cells. Glucose induces a sequential
      formation of cADPR and NAADP. Pretreatment with jasplakinolide, an actin
      polymerizing agent, or a myosin heavy chain IIA (MHCIIA) blocker, blebbistatin,
      inhibited glucose-induced CD38 internalization, an essential step for cADPR
      formation. Blocking actin disassembly with jasplakinolide also abrogates glucose
      induced cADPR and NAADP formation and sustained Ca(2+) signals. These results
      indicate that actin filaments along with MHCIIA play an important role in CD38
      internalization for the generation of Ca(2+) mobilizing messengers for glucose
      induced Ca(2+) signaling in pancreatic beta-cells.

PMID- 22627739
TI  - The European Consensus on grading of bone marrow fibrosis allows a better
      prognostication of patients with primary myelofibrosis.
AB  - We investigated the relationship between the International Prognostic Scoring
      System of the International Working Group for Myelofibrosis Research and
      Treatment and the European Consensus on grading of bone marrow fibrosis (MF) in
      patients with primary myelofibrosis. We compared them in 196 consecutive primary
      myelofibrosis patients (median follow-up 45.7 months; range 7.4-159).
      International Prognostic Scoring System classified 42 cases as low risk, 73 as
      intermediate risk-1, 69 as intermediate risk-2, and 12 as high risk; European
      Consensus on grading of bone marrow fibrosis classified 83 cases as MF-0, 58 as
      MF-1, 41 as MF-2, and 14 as MF-3. By the time of the analysis, 30 patients
      (15.3%) had died. Overall median survival was 3.8 years (95% confidence interval:
      3.3-4.3). Multivariate analysis confirmed that both scoring systems independently
      predicted survival, with hazard ratios similar to those provided by univariate
      analysis (respectively, 2.40 (95% confidence interval: 1.47-3.91) and 2.58 (95%
      confidence interval: 1.72-3.89) but the likelihood ratio increased from 19.6 of
      the International Prognostic Scoring System or 29.0 of the European Consensus on
      grading of bone MF to 42.3 when both measures were considered together. Analysis
      of the overall survival curves documented that patients classified as having the
      most favourable rate with both prognostic scores (ie low risk and MF-0) survive
      longer than those with only one favourable score (ie low risk but MF >0 or MF-0,
      but International Prognostic Scoring System >low risk). In contrast, those
      patients classified as having the most unfavourable rate for both scores (high
      risk and MF-3) have a shorter survival than those with only one unfavourable
      score (ie high risk but MF<3 or MF-3, but International Prognostic Scoring System
      <high risk). In conclusion, our analysis suggests that better prognostication can
      be achieved in primary myelofibrosis patients when both systems are used
      together.

PMID- 22627740
TI  - Accurate detection of the tumor clone in peripheral T-cell lymphoma biopsies by
      flow cytometric analysis of TCR-Vbeta repertoire.
AB  - Multiparametric flow cytometry has proven to be a powerful method for detection
      and immunophenotypic characterization of clonal subsets, particularly in
      lymphoproliferative disorders of the B-cell lineage. Although in theory
      promising, this approach has not been comparably fulfilled in mature T-cell
      malignancies. Specifically, the T-cell receptor-Vbeta repertoire analysis in
      blood can provide strong evidence of clonality, particularly when a single
      expanded Vbeta family is detected. The purpose of this study was to determine the
      relevance of this approach when applied to biopsies, at the site of tumor
      involvement. To this end, 30 peripheral T-cell lymphoma and 94 control biopsies
      were prospectively studied. Vbeta expansions were commonly detected within CD4+
      or CD8+ T cells (97% of peripheral T-cell lymphoma and 54% of non-peripheral T
      cell lymphoma cases); thus, not differentiating malignant from reactive
      processes. Interestingly, we demonstrated that using a standardized evaluation,
      the detection of a high Vbeta expansion was closely associated with diagnosis of
      peripheral T-cell lymphoma, with remarkable specificity (98%) and sensitivity
      (90%). This approach also identified eight cases of peripheral T-cell lymphoma
      that were not detectable by other forms of immunophenotyping. Moreover, focusing
      Vbeta expression analysis to T-cell subsets with aberrant immunophenotypes, we
      demonstrated that the T-cell clone might be heterogeneous with regard to surface
      CD7 or CD10 expression (4/11 cases), providing indication on 'phenotypic
      plasticity'. Finally, among the wide variety of Vbeta families, the occurrence of
      a Vbeta17 expansion in five cases was striking. To our knowledge, this is the
      first report demonstrating the power of T-cell receptor-Vbeta repertoire analysis
      by flow cytometry in biopsies as a basis for peripheral T-cell lymphoma diagnosis
      and precise T-cell clone identification and characterization.

PMID- 22627741
TI  - Parameters predicting lymph node metastasis in patients with superficial
      esophageal squamous cell carcinoma.
AB  - Endoscopic resection is a less invasive treatment than esophagectomy for
      superficial esophageal squamous cell carcinoma, but patients with lymph node
      metastasis need additional treatment after endoscopic resection. The purpose of
      this study was to establish a set of indicators to identify superficial
      esophageal squamous cell carcinoma patients at a high risk of metastasis. In all,
      271 superficial esophageal squamous cell carcinoma esophagectomy cases were
      reviewed retrospectively. The relationships between clinicopathological
      parameters and immunohistochemical findings (p53, cyclin D1, EGFR and VEGF) on
      tissue microarrays, on the one hand, and lymph node metastasis were assessed by
      univariate and multivariate logistic regression analyses. Patients with
      intraluminal masses and ulcerated masses had a high risk of lymph node
      metastasis. Patients with superficial esophageal squamous cell carcinoma (1)
      thinner than 1200 MUm; (2) confined to the mucosa; (3) with submucosal invasion
      <250 MUm; (4) with submucosal invasion >=250 MUm but with negative VEGF
      expression and well/moderately differentiated or basaloid histology; or (5) with
      submucosal invasion >=250 MUm but with weak VEGF expression and well
      differentiated histology had almost no risk of lymph node metastasis. We
      recommend endoscopic resection for all erosive, papillary and plaque-like
      superficial esophageal squamous cell carcinomas where endoscopic resection is
      clinically feasible, and esophagectomy for all other erosive, papillary and
      plaque-like cases and all intraluminal masses and ulcerated tumors. No additional
      treatment is needed for endoscopic resection cases with superficial esophageal
      squamous cell carcinoma (1) thinner than 1200 MUm; (2) confined to the mucosa;
      (3) with submucosal invasion <250 MUm; (4) with submucosal invasion >=250 MUm but
      with negative VEGF expression and well/moderately differentiated or basaloid
      histology; or (5) with submucosal invasion >=250 MUm but with weak VEGF
      expression and well-differentiated histology. These clinical and pathological
      criteria should enable more accurate selection of patients for these procedures.

PMID- 22627742
TI  - Infectious mononucleosis mimicking lymphoma: distinguishing morphological and
      immunophenotypic features.
AB  - The diagnosis of infectious mononucleosis (acute Epstein-Barr virus (EBV)
      infection) is usually made on the basis of clinical and laboratory findings.
      However, an atypical clinical presentation occasionally results in a lymph node
      or tonsillar biopsy. The morphological features of EBV-infected lymphoid tissue
      can easily mimic lymphoma. Furthermore, the immunophenotype of the immunoblasts
      has not been well characterized. To assess the morphological spectrum of acute
      EBV infection and the utility of immunohistochemistry in diagnosing difficult
      cases that resemble lymphoma, we reviewed 18 cases of acute EBV infection
      submitted in consultation to our institution with an initial diagnosis of/or
      suspicion for lymphoma. Patients included nine male and nine female individuals
      with a median age of 18 years (range 9-69). Biopsies were obtained from lymph
      nodes (3/18) or Waldeyer's ring (15/18). Infectious mononucleosis was confirmed
      by monospot or serological assays in 72% of cases (13/18). All cases featured
      architectural distortion by a polymorphous infiltrate with an immunoblastic
      proliferation, sometimes forming sheets. Reed-Sternberg-like cells were present
      in 8/18 (44%) of the cases. Infiltrates were often accompanied by necrosis
      (10/18) and mucosal ulceration (6/15). The majority of immunoblasts in all cases
      were CD20+ B cells with a post-germinal center immunophenotype (strongly positive
      for MUM1/IRF4 (18/18), CD10- (18/18 negative) and BCL-6- (16/18 negative; 2/18
      faint BCL-6 expression in <10% of immunoblasts)). Immunoblasts showed variable
      weak expression of BCL-2 and polyclonal expression of kappa and lambda
      immunoglobulin light chains in 81% cases. Reed-Sternberg-like cells in 8/8 cases
      were CD30+, CD15-, BOB.1+ and OCT-2+. In conclusion, an atypical lymphoid
      infiltrate with numerous MUM1+, CD10-, BCL-6- immunoblasts should raise the
      suspicion of a reactive process, such as infectious mononucleosis, and warrants
      additional consideration before a diagnosis of lymphoma is made.

PMID- 22627743
TI  - Effects of dietary methionine source on productive performance, blood chemical,
      and hematological profiles in broiler chickens under tropical conditions.
AB  - This study was conducted to investigate the effects of supplementation of DL
      methionine (DLM) and liquid DL-methionine hydroxy analog free acid (MHA) in diets
      on productive performance, blood chemical, and hematological profiles in broiler
      chickens under tropical conditions. In all, 216 commercial male broiler chicks
      were used to compare two dietary methionine sources, DLM and MHA. Chicks were
      raised for 35 days in battery cages situated in high ambient temperature and
      relative humidity open-side housing. The chicks were divided into three
      treatments in six replications with 12 chicks each. A completely randomized
      design was used. The treatment groups were (1) control group (methionine and
      total sulfur amino acid deficient diet), (2) supplementation of DLM as the
      methionine source in diet, and (3) supplementation of MHA as the methionine
      source in diet. The productive performance of DLM and MHA was not significantly
      different. Both supplementation of DLM and MHA significantly improved final body
      weight, body weight gain, average daily gain, and feed conversion ratio when
      compared to the control group (P < 0.01). Both DLM and MHA supplementation
      significantly increased the plasma cystine concentration level (P < 0.05). The
      use of DLM enhanced the plasma methionine concentration (P < 0.01) and increased
      the heterophil/lymphocyte ratio (P < 0.05). While MHA elevated the plasma taurine
      and uric acid concentration levels (P < 0.05). In conclusion, under tropical
      conditions, there was no significant difference between DLM and MHA
      supplementation on productive performance; plasma methionine concentration was
      increased by DLM supplementation, while plasma taurine and uric acid
      concentration were significantly increased by MHA supplementation.

PMID- 22627744
TI  - Metal-free arylation of benzene and pyridine promoted by amino-linked nitrogen
      heterocyclic carbenes.
AB  - An amino-linked nitrogen heterocyclic carbene (amino-NHC), 1-tBu, has been shown
      to mediate carbon-carbon coupling through the direct C-H functionalization of
      benzene and pyridine in the absence of a metal catalyst. Using EPR, the first
      spectroscopic evidence corroborating the single electron transfer mechanism for
      the metal-free carbon-carbon coupling manifold, as reported by others, is
      introduced.

PMID- 22627745
TI  - [Precipitating factors of migraine attacks in patients attended in neurology
      services. The FACTOR study].
AB  - INTRODUCTION: Patients with migraine often report factors or circumstances that
      precipitate or trigger their attacks. Yet few studies have been conducted to
      examine this matter. AIM: To explore the factors that precipitate migraine in our
      setting, as well is their possible relation with the intensity of the attacks or
      the overall repercussion of migraine. PATIENTS AND METHODS: An epidemiological,
      cross-sectional, multi-centre study was conducted in neurology consultation
      services. Sociodemographic and clinical data were collected and the precipitating
      factors were identified from a closed list. The specific migraine disability
      questionnaire -Headache Impact Test (HIT-6)- and the measurement of the number of
      lost workday equivalents were used in the study. RESULTS: Altogether 817 patients
      were recruited (72.5% females, mean age: 34.6 +/- 10.3 years). A total of 70.5%
      of the patients had severe disability according to the HIT-6. The mean monthly
      number of lost workday equivalents was 2.1 +/- 2.5. A total of 96.6% of the
      patients identified some precipitating factor for the attacks, the most commonly
      reported being hormonal (75.2%), stress (70.9%) and those related with disorders
      affecting sleep patterns (68.4%). CONCLUSIONS: The FACTOR study confirms that
      most patients with migraine identify some circumstance that precipitates their
      attacks. Controlling or avoiding these factors, whenever possible, must be part
      of the programme of education received by patients suffering from migraine.

PMID- 22627746
TI  - [Prefrontal Symptoms Inventory for clinical evaluation of addictions in everyday
      life: development process and psychometric properties].
AB  - INTRODUCTION: Research has provided evidence of the presence of prefrontal
      symptoms in addicts, although they are usually evaluated using questionnaires
      that were created for acquired brain injury. AIMS: To produce a specific
      instrument for evaluating those symptoms in subjects with addictions. SUBJECTS
      AND METHODS: For the study, 1624 participants were recruited (445 addicts and
      1179 from the general population) and were given a 100-item inventory to complete
      based on the three spheres of human activity (cognition, emotion and behaviour)
      in relation to the three great prefrontal syndromes (dorsolateral, ventromedial
      and orbital). The preliminary analyses ruled out those that did not prove to have
      sufficient discriminating power, which resulted in the Prefrontal Symptoms
      Inventory (PSI) consisting of 46 items. The Dysexecutive Questionnaire (DEX-Sp)
      and the Perceived Stress Scale (PSS) were administered in order to study the
      convergent validity. RESULTS: The data show the three-factor structure of the
      questionnaire: problems with executive control (with three sub-factors: problems
      with motivation, control and attention), problems with social behaviour and
      problems with emotional control. The relationships between the scores on the PSI
      and sociodemographic and consumption variables, as well as with the DEX-Sp and
      the PSS were analysed. A reduced 20-item version is provided for screening.
      CONCLUSIONS: The PSI relates the ('subject-centred') self-evaluation of persons
      with the a priori ('brain-centred') theoretical formulation, the results showing
      adequate psychometric properties. We recommend its use when it comes to exploring
      the prefrontal symptoms of addicts, as well as other clinical or subclinical
      populations with similar cognitive profiles.

PMID- 22627747
TI  - [Involvement of cocaine in cerebral vascular pathology].
AB  - AIM: To describe the involvement of cocaine in cerebral vascular pathology in
      young patients. PATIENTS AND METHODS: The work consists in a descriptive study of
      the role of cocaine in patients with acute stroke under the age of 50 years
      admitted to the neurology service over a period of four years. Eighteen patients
      with positive levels of cocaine on admission and 79 patients with negative levels
      were analysed. Different variables that define the profile of vascular risk,
      characteristics of the stroke and the morbidity and mortality associated to them
      are collected and analysed. RESULTS: Males were predominant and there was a non
      significant higher proportion of vascular risk factors in the control group
      (55.6% versus 64.6%). The group of consumers presented a significantly lower mean
      age (35.2 +/- 8.9 versus 41.5 +/- 7.7 years), higher consumption of toxic
      substances (tobacco, alcohol and cannabis), hyperCKemia (27.8% versus 5.1%) and
      psychiatric disorders (16.7% versus 3.8%) (p < 0.05). The ischaemic stroke in the
      anterior territory subtype was predominant in both groups. There was a clear
      tendency towards normality in complementary tests and a higher rate of
      complications (33.3% versus 15.2%) and mortality (11.1% versus 3.8%) among
      consumers (p > 0.05). CONCLUSIONS: Cocaine is a risk factor that must be taken
      into account in young adults: it is associated to stroke at earlier ages than is
      considered normal, with a tendency towards normality in complementary tests and a
      higher rate of hospital morbidity and mortality.

PMID- 22627748
TI  - [Metastatic plexus papilloma in the paediatric age: a case report and review of
      the literature].
AB  - INTRODUCTION: Tumours of the choroid plexus are uncommon, with a peak incidence
      in the early years of life. Clinically they usually produce intracranial
      hypertension. Histologically, they can be divided into papillomas and carcinomas.
      Metastasis rarely occurs in the case of papillomas. CASE REPORT: An 11-year-old
      female with an intracranial lesion in the 4th ventricle and a sacral intradural
      lesion. A sub-occipital craniotomy with total resection of the ventricular lesion
      was performed and this was followed later by partial exeresis of the spinal
      lesion. The histological study provides the diagnosis of typical choroid plexus
      papilloma in the intracranial lesion and choroid plexus papilloma metastasis in
      the spinal lesion. A review of the literature showed that choroid plexus
      papillomas with metastatic lesions are very rarely found at the paediatric age.
      There is no general agreement on the treatment of plexus papilloma metastasis at
      the paediatric age, expectant management being adopted in two cases and surgical
      treatment involving a laminectomy in the other. CONCLUSIONS: Choroid plexus
      papillomas are rare, benign lesions with a good prognosis. Metastasis seldom
      exists. Preferred treatment is total resection of the lesion. For the treatment
      of metastases, there is no evidence as to which is the best approach and
      different alternatives have been suggested.

PMID- 22627749
TI  - Review of the novelties presented at the 27th Congress of the European Committee
      for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).
AB  - The new insights presented at the 5th Joint Triennial Congress of the European
      and Americas Committees on Treatment and Research in Multiple Sclerosis (ECTRIMS
      and ACTRIMS) held in Amsterdam, the Netherlands, 19-22 October 2011, have been
      summarized at the fourth edition of Post-ECTRIMS meeting held in Madrid in
      November 2011. Further evidence from epidemiological studies yield a possible
      relationship between nutrition and alterations of the microbiota that may result
      in the development of multiple sclerosis (MS) and that may trigger the
      exacerbation of disease symptoms. Also show the magnitude of impact of
      comorbidities in multiple sclerosis course as well as the impact of early
      identification and management. Review of current data on chronic cerebrospinal
      venous insufficiency and MS sclerosis concludes that there is no role of chronic
      cerebrospinal venous insufficiency in either multiple sclerosis risk or MS
      severity. New diagnostic criteria for MS have simplified requirements for
      demonstrating dissemination of lesions in time. High-field magnetic resonance
      imaging improves cortical visualization and become a promising tool to detect
      remyelinization and cortical and medullary lesions, and optical coherence
      tomography is established as a powerful tool for neuroprotection trials. Diffuse
      meningeal inflammation through B-cell follicle-like structures is associated with
      cortical pathology and an accelerated clinical course in secondary progressive MS
      sclerosis. Systemic inflammation may contribute to neurodegeneration processes in
      MS, and with regard to grey matter damage recent findings conclude that occurs
      early in disease course, and correlates with future MS-related disability.

PMID- 22627750
TI  - [Whole genome sequencing: a qualitative leap forward in genetic studies].
AB  - At the present time the so-called parallel or next generation sequencing (NGS)
      technique is rapidly expanding and developing; this process establishes a jump by
      several orders of magnitude in the length of the fragments sequenced and the
      speed with which this sequencing is carried out. NGS allows a whole human genome
      to be sequenced in the same amount of time and with the same economic cost
      required to sequence two or three large genes using the Sanger technique. Use of
      NGS allows us to go from examining specific genes selected by studying the
      phenotype to exploring whole genomes of groups of humans or other species. This
      is making it possible to know not only what an individual genome is like but also
      how the human genome changes from one person to another, how genomes differ from
      one group of humans to another, and even how the genome differs in a tumour with
      respect to the healthy genome of the host.

PMID- 22627751
TI  - [Usefulness of neurosonology in the diagnosis of acute hydrocephalus].

PMID- 22627752
TI  - [Multiple mononeuritis and polyneuropathy in Chagas disease].

PMID- 22627753
TI  - [Angelman syndrome and fear of walking. Psychomotor involution?].

PMID- 22627754
TI  - Is serum microRNA better specific marker for systemic lupus erythematosus?

PMID- 22627755
TI  - IL-17: a potential therapeutic target for rheumatoid arthritis?

PMID- 22627756
TI  - Acute abdomen in a septuagenarian.

PMID- 22627758
TI  - Production and characterization of human granulocyte-macrophage colony
      stimulating factor (hGM-CSF) expressed in the oleaginous yeast Yarrowia
      lipolytica.
AB  - Since its isolation, the human granulocyte-macrophage colony-stimulating factor
      (hGM-CSF) has been proposed as a new class of therapeutic biological products in
      the treatment of various diseases. However, the toxicity of this cytokine towards
      its expression host constitutes a major obstacle to bioprocess development for
      large-scale production. In this work, the optimized gene encoding hGM-CSF was
      expressed in the yeast Yarrowia lipolytica in one and two copies under the
      control of the fatty acid-inducible POX2 promoter. Protein secretion was directed
      by the targeting sequence of the extracellular lipase (LIP2): preXALip2. After 48
      h of induction, Western blot analysis revealed the presence of a nonglycosylated
      form of 14.5 kDa and a trail of hGM-CSF hyperglycosylated varying from 23 kDa to
      more than 60 kDa. The two-copy transformants produced hGM-CSF level which was
      sevenfold higher compared to the single-copy ones. Deglycosylation with PNGase F
      showed two forms: a mature form of 14.5 kDa and an unprocessed form of 18 kDa.
      The addition of two alanines to the signal sequence resulted in correct hGM-CSF
      processing. The production level was estimated at 250 mg/l after preliminary
      optimization studies of the cultivation and induction phases. The purified hGM
      CSF was identified by N-terminal sequencing and LC-MS/MS analysis; its biological
      activity was confirmed by stimulating the proliferation of TF1 cell line. This
      study demonstrated that Y. lipolytica is a promising host for the efficient
      production of active toxic proteins like hGM-CSF.

PMID- 22627757
TI  - Molecular genetic analysis reveals that a nonribosomal peptide synthetase-like
      (NRPS-like) gene in Aspergillus nidulans is responsible for microperfuranone
      biosynthesis.
AB  - Genome sequencing of Aspergillus species including Aspergillus nidulans has
      revealed that there are far more secondary metabolite biosynthetic gene clusters
      than secondary metabolites isolated from these organisms. This implies that these
      organisms can produce additional secondary metabolites, which have not yet been
      elucidated. The A. nidulans genome contains 12 nonribosomal peptide synthetase
      (NRPS), one hybrid polyketide synthase/NRPS, and 14 NRPS-like genes. The only
      NRPS-like gene in A. nidulans with a known product is tdiA, which is involved in
      terrequinone A biosynthesis. To attempt to identify the products of these NRPS
      like genes, we replaced the native promoters of the NRPS-like genes with the
      inducible alcohol dehydrogenase (alcA) promoter. Our results demonstrated that
      induction of the single NRPS-like gene AN3396.4 led to the enhanced production of
      microperfuranone. Furthermore, heterologous expression of AN3396.4 in Aspergillus
      niger confirmed that only one NRPS-like gene, AN3396.4, is necessary for the
      production of microperfuranone.

PMID- 22627759
TI  - Application of purified recombinant antigenic spike fragments to the diagnosis of
      avian infectious bronchitis virus infection.
AB  - The spike (S) protein, containing two subunits, S1 and S2, is the major immunity
      eliciting antigen of avian infectious bronchitis virus (IBV), a highly contagious
      disease of chickens. Several immunogenic regions, mainly located within the S1
      subunit, have been identified. Nonetheless, these immune-dominant regions were
      defined using selected monoclonal antibodies or using a short peptide approach
      that involves only certain limited regions of the S protein. In addition, some
      immune-dominant regions are located in hypervariable regions (HVRs) which are not
      present in all serotypes. Hence, the aim of this study was to determine a broader
      range of antigenic regions that have strong antibody eliciting ability; these
      could then be applied for development of an IBV-diagnostic tool. Initially, the
      S1 and part of the S2 subunit protein (24-567 amino acids) were expressed as five
      fragments in prokaryotic system. The antigenicity was confirmed using IBV
      immunized sera. Performance of the S subfragments was evaluated by ELISA using a
      panel of field chicken sera with known IBV titres determined by a commercial kit.
      This indicated that, among the five antigenic recombinant proteins, the region S
      E showed the highest specificity and sensitivity, namely 95.38 % and 96.29 %,
      respectively. The kappa value for the in-house ELISA using the S-E fragment
      compared to a commercial kit was 0.9172, indicating a high agreement between
      these two methods. As region S-E harbors strong immunogenicity within the spike
      protein, it has the potential to be exploited as an antigen when developing a
      cost-effective ELISA-based diagnosis tool.

PMID- 22627760
TI  - Phosphoproteomic investigation of a solvent producing bacterium Clostridium
      acetobutylicum.
AB  - In this study, we employed TiO2 enrichment and high accuracy liquid
      chromatography-mass spectrometry-mass spectrometry to identify the
      phosphoproteome of Clostridium acetobutyicum ATCC824 in acidogenesis and
      solventogenesis. As many as 82 phosphopeptides in 61 proteins, with 107
      phosphorylated sites on serine, threonine, or tyrosine, were identified with high
      confidence. We detected 52 phosphopeptides from 44 proteins in acidogenesis and
      70 phosphopeptides from 51 proteins in solventogenesis, respectively.
      Bioinformatic analysis revealed most of the phosphoproteins located in cytoplasm
      and participated in carbon metabolism. Based on comparison between the two
      stages, we found 27 stage-specific phosphorylated proteins (10 in acidogenesis
      and 17 in solventogenesis), some of which were solvent production-related enzymes
      and metabolic regulators, showed significantly different phosphorylated status.
      Further analysis indicated that protein phosphorylation could be involved in the
      shift of stages or in solvent production pathway directly. Comparison against
      several other organisms revealed the evolutionary diversity among them on
      phosphorylation level in spite of their high homology on protein sequence level.

PMID- 22627761
TI  - Lyophilised reconstituted human platelets increase thrombus formation in a
      clinical ex vivo model of deep arterial injury.
AB  - Platelets are the principal component of the innate haemostatic system that
      protect from traumatic bleeding. We investigated whether lyophilised human
      platelets (LHPs) could enhance clot formation within platelet-free and whole
      blood environments using an ex vivo model of deep arterial injury. Lyophilised
      human platelets were produced from stored human platelets and characterised using
      conventional, fluorescent and electron microscopic techniques. LHPs were
      resuspended in platelet-free plasma (PFP) obtained from citrated whole human
      blood to form final concentrations of 0, 20 and 200 x 109 LHPs/L. LHPs with
      recalcified PFP or whole blood were perfused through the chamber at low (212 s-1)
      and high (1,690 s-1) shear rates with porcine aortic tunica media as thrombogenic
      substrate. LHPs shared morphological characteristics with native human platelets
      and were incorporated into clot generated from PFP or whole blood.
      Histomorphometrically measured mean thrombus area increased in a dose-dependent
      manner following the addition of LHPs to PFP under conditions of high shear [704
      MUm2 +/- 186 MUm2 (mean +/- SEM), 1,511 MUm2 +/- 320 MUm2 and 2,378 MUm2 +/- 315
      MUm2, for LHPs at 0, 20 and 200 x 109 /l, respectively (p= 0.012)]. Lyophilised
      human platelets retain haemostatic properties when reconstituted in both PFP and
      whole blood, and enhance thrombus formation in a model of deep arterial injury.
      These data suggest that LHPs have the potential to serve as a therapeutic
      intervention during haemorrhage under circumstances of trauma, and platelet
      depletion or dysfunction.

PMID- 22627765
TI  - Distinct roles for long-term hematopoietic stem cells and erythroid precursor
      cells in a murine model of Jak2V617F-mediated polycythemia vera.
AB  - In the current model of the pathogenesis of polycythemia vera (PV), the JAK2V617F
      mutation arises in hematopoietic stem cells (HSCs) that maintain the disease,
      while erythroid precursor populations expand, resulting in excessive red blood
      cell production. We examined the role of these specific cell populations using a
      conditional Jak2V617F knockin murine model. We demonstrate that the most immature
      long-term (LT) HSCs are solely responsible for initiating and maintaining the
      disease in vivo and that Jak2V617F mutant LT-HSCs dominate hematopoiesis over
      time. When we induced Jak2V617F expression in erythropoietin receptor expressing
      precursor cells, the mice developed elevated hematocrit, expanded erythroid
      precursors, and suppressed erythropoietin levels. However, the disease phenotype
      was significantly attenuated compared with mice expressing Jak2V617F in LT-HSCs.
      In addition to developing a PV phenotype, all mice transplanted with Jak2V617F LT
      HSCs underwent myelofibrotic transformation over time. These findings
      recapitulate the development of post-PV myelofibrosis in human myeloproliferative
      neoplasms. In aggregate, these results demonstrate the distinct roles of LT-HSCs
      and erythroid precursors in the pathogenesis of PV.

PMID- 22627766
TI  - Eltrombopag inhibits the proliferation of leukemia cells via reduction of
      intracellular iron and induction of differentiation.
AB  - Eltrombopag (EP) is a small-molecule, nonpeptide thrombopoietin receptor (TPO-R)
      agonist that has been approved recently for the treatment of thrombocytopenia in
      patients with chronic immune thrombocytopenic purpura. Prior studies have shown
      that EP stimulates megakaryopoiesis in BM cells from patients with acute myeloid
      leukemia and myelodysplastic syndrome, and the results also suggested that it may
      inhibit leukemia cell growth. In the present study, we studied the effects of EP
      on leukemia cell proliferation and the mechanism of its antiproliferative
      effects. We found that EP leads to a decreased cell division rate, a block in
      G(1) phase of cell cycle, and increased differentiation in human and murine
      leukemia cells. Because EP is species specific in that it can only bind TPO-R in
      human and primate cells, these findings further suggested that the antileukemic
      effect is independent of TPO-R. We found that treatment with EP leads to a
      reduction in free intracellular iron in leukemic cells in a dose-dependent
      manner. Experimental increase of intracellular iron abrogated the
      antiproliferative and differentiation-inducing effects of EP, demonstrating that
      its antileukemic effects are mediated through modulation of intracellular iron
      content. Finally, determination of EP's antileukemic activity in vivo
      demonstrated its ability to prolong survival in 2 mouse models of leukemia.

PMID- 22627768
TI  - PV-1 is recognized by the PAL-E antibody and forms complexes with NRP-1.
AB  - Pathologische anatomie leiden endothelium (PAL-E) antibody has been used for more
      than 20 years as a prototype marker for vascular endothelium. The elusive target
      of this antibody has been claimed to be plasmalemma vesicle-associated protein-1
      (PV-1) and neuropilin-1 (NRP-1). Using immunofluorescence, we show that PAL-E,
      anti-PV-1, anti-NRP-1, and anti-CD31 antibodies show largely identical staining
      patterns in the vasculature of different tissues. However, PV-1-transfected cells
      only bind PAL-E and anti-PV-1 antibodies, whereas NRP-1 transfectants stain with
      anti-NRP-1 antibodies in flow cytometry. Using lysates from tissues and
      transfected cells, we further confirm that the molecule recognized by PAL-E and
      anti-PV-1 antibodies is not NRP-1 but PV-1. Nevertheless, coimmunoprecipitation
      studies unambiguously demonstrate that NRP-1 can form complexes with PV-1. This
      connects, for the first time, 2 molecules involved in leukocyte trafficking and
      angiogenesis, thereby opening interesting possibilities for future research in
      this field.

PMID- 22627767
TI  - Sox4 cooperates with CREB in myeloid transformation.
AB  - The cAMP response element-binding protein (CREB) is a nuclear transcription
      factor that is critical for normal and neoplastic hematopoiesis. Previous studies
      have demonstrated that CREB is a proto-oncogene whose overexpression promotes
      cellular proliferation in hematopoietic cells. Transgenic mice that overexpress
      CREB in myeloid cells develop a myeloproliferative disease with splenomegaly and
      aberrant myelopoiesis. However, CREB overexpressing mice do not spontaneously
      develop acute myeloid leukemia. In this study, we used retroviral insertional
      mutagenesis to identify genes that accelerate leukemia in CREB transgenic mice.
      Our mutagenesis screen identified several integration sites, including oncogenes
      Gfi1, Myb, and Ras. The Sox4 transcription factor was identified by our screen as
      a gene that cooperates with CREB in myeloid leukemogenesis. We show that the
      transduction of CREB transgenic mouse bone marrow cells with a Sox4 retrovirus
      increases survival and self-renewal of cells in vitro. Furthermore, leukemic
      blasts from the majority of acute myeloid leukemia patients have higher CREB,
      phosphorylated CREB, and Sox 4 protein expression. Sox4 transduction of mouse
      bone marrow cells results in increased expression of CREB target genes. We also
      demonstrate that CREB is a direct target of Sox4 by chromatin immunoprecipitation
      assays. These results indicate that Sox4 and CREB cooperate and contribute to
      increased proliferation of hematopoietic progenitor cells.

PMID- 22627769
TI  - Inducible expression and pathophysiologic functions of T-plastin in cutaneous T
      cell lymphoma.
AB  - A molecular feature of Sezary syndrome (SS) is the abnormal expression of T
      plastin by malignant T cells. Herein, we investigated the molecular mechanisms
      involved in T-plastin synthesis and the functions of this actin-binding protein,
      with a special interest in chemoresistance and migration. We confirm the specific
      expression of T-plastin in peripheral blood lymphocytes (PBLs) from SS patients
      and its total absence in PBLs from patients with mycosis fungoides, inflammatory
      cutaneous or hematologic diseases, and from healthy volunteers. Only 3 of 4 SS
      patients did constitutively express T-plastin. To assess whether T-plastin
      expression was inducible, T-plastin-negative PBLs were stimulated by phorbol 12
      myristate 13-acetate and ionomycin. Our results demonstrate that T-plastin
      synthesis was induced in negative PBLs from SS patients, other studied patients,
      and healthy volunteers. Both constitutive and calcium-induced T-plastin
      expression was down-regulated by calcineurin inhibitors and involved nuclear
      factor of activated T cells transcription pathway. Constitutive T-plastin
      expression in SS was associated with resistance to etoposide-induced apoptosis
      and cell migration toward chemokines (TARC/CCL17, IP-10). In conclusion, T
      plastin is a marker restricted to malignant lymphocytes from SS patients and
      plays a role for cell survival and migration. This opens new strategies for the
      treatment of SS advanced stages.

PMID- 22627770
TI  - Transmaternal cell flow leads to antigen-experienced cord blood.
AB  - Umbilical cord blood (UCB) is used for HSCT. It is known that UCB can comprise Ag
      specific T cells. Here we question whether solely transmaternal cell flow may
      immunize UCB. Twenty-three female UCB samples were collected from healthy mothers
      and analyzed for minor histocompatibility Ag HY-specific responses. Forty-two of
      104 tetramer(pos) T-cell clones, isolated from 16 of 17 UCB samples, showed male
      specific lysis in vitro. Male microchimerism was present in 6 of 12 UCB samples
      analyzed. In conclusion, female UCB comprises HY-specific cytotoxic T cells. The
      immunization is presumably caused by transmaternal cell flow of male
      microchimerism present in the mother. The presence of immune cells in UCB that
      are not directed against maternal foreign Ags is remarkable and may explain the
      reported clinical observation of improved HSCT outcome with younger sibling
      donors.

PMID- 22627774
TI  - Antisense-targeted immuno-EM localization of the pre-mRNA path in the
      spliceosomal C complex.
AB  - A first step in understanding the architecture of the spliceosome is elucidating
      the positions of individual spliceosomal components and functional centers.
      Catalysis of the first step of pre-mRNA splicing leads to the formation of the
      spliceosomal C complex, which contains the pre-mRNA intermediates--the cleaved 5'
      exon and the intron-3' exon lariat. To topographically locate the catalytic
      center of the human C complex, we first determined, by DNA oligonucleotide
      directed RNAse H digestions, accessible pre-mRNA regions closest to nucleotides
      of the cleaved 5' splice site (i.e., the 3' end of exon 1 and the 5' end of the
      intron) and the intron lariat branch point, which are expected to be at/near the
      catalytic center in complex C. For electron microscopy (EM) localization studies,
      C complexes were allowed to form, and biotinylated 2'-OMe RNA oligonucleotides
      were annealed to these accessible regions. To allow localization by EM of the
      bound oligonucleotide, first antibiotin antibodies and then protein A-coated
      colloidal gold were additionally bound. EM analyses allowed us to map the
      position of exon and intron nucleotides near the cleaved 5' splice site, as well
      as close to the anchoring site just upstream of the branch adenosine. The
      identified positions in the C complex EM map give first hints as to the path of
      the pre-mRNA splicing intermediates in an active spliceosomal C complex and
      further define a possible location for its catalytic center.

PMID- 22627775
TI  - Alternative splicing and trans-splicing events revealed by analysis of the Bombyx
      mori transcriptome.
AB  - Alternative splicing and trans-splicing events have not been systematically
      studied in the silkworm Bombyx mori. Here, the silkworm transcriptome was
      analyzed by RNA-seq. We identified 320 novel genes, modified 1140 gene models,
      and found thousands of alternative splicing and 58 trans-splicing events. Studies
      of three SR proteins show that both their alternative splicing patterns and mRNA
      products are conserved from insect to human, and one isoform of Srsf6 with a
      retained intron is expressed sex-specifically in silkworm gonads. Trans-splicing
      of mod(mdg4) in silkworm was experimentally confirmed. We identified integrations
      from a common 5'-gene with 46 newly identified alternative 3'-exons that are
      located on both DNA strands over a 500-kb region. Other trans-splicing events in
      B. mori were predicted by bioinformatic analysis, in which 12 events were
      confirmed by RT-PCR, six events were further validated by chimeric SNPs, and two
      events were confirmed by allele-specific RT-PCR in F(1) hybrids from distinct
      silkworm lines of JS and L10, indicating that trans-splicing is more widespread
      in insects than previously thought. Analysis of the B. mori transcriptome by RNA
      seq provides valuable information of regulatory alternative splicing events. The
      conservation of splicing events across species and newly identified trans
      splicing events suggest that B. mori is a good model for future studies.

PMID- 22627776
TI  - Analysis of fumonisins B1 and B2 in spices and aromatic and medicinal herbs by
      HPLC-FLD with on-line post-column derivatization and positive confirmation by LC
      MS/MS.
AB  - Fumonisins are produced by the fungus Fusarium verticillioides, which are known
      to cause fatal diseases in some animals and humans. Here, we describe a
      sensitive, reproducible and reliable analytical method for the quantitative
      determination of fumonisins B(1) (FB(1)) and B(2) (FB(2)) in 112 spices and
      aromatic and medicinal herbs marketed in China. This method is based on high
      performance liquid chromatography and fluorescence detection (HPLC-FLD) coupled
      to a new on-line post-column derivatization using ortho-phthaldialdehyde with 2
      mercaptoethanol and immunoaffinity column clean-up. Under the optimized
      experimental conditions, a complete separation of FB(1) and FB(2) was obtained
      using a Synergi C(18) column and a gradient elution at 0.8 mL min(-1) with
      methanol and 0.1 M phosphate buffer at pH 3.15. The limits of detection for FB(1)
      and FB(2) were both 40 MUg kg(-1). Good recoveries were found for spiked samples
      with FB(1) and FB(2), ranging from 82.34% to 98.16% for FB(1) and from 72.58% to
      97.10% for FB(2), with relative standard deviation (RSD) < 7.0%. 5 spices, 11
      aromatic herbs and 96 medicinal herbs including 93 normal samples and 19 visibly
      moldy samples, which were spoiled artificially, were analyzed. The results showed
      that 8 (42.1%) visibly moldy samples and 8 (8.6%) normal samples were
      contaminated with FB(1) at mean contents of 129.0 and 165.9 MUg kg(-1), and with
      FB(2) at 1745.0 and 256.8 MUg kg(-1), respectively. Positive confirmation of
      detected samples was performed by liquid chromatography tandem electrospray
      ionization mass spectrometry (LC-ESI-MS/MS), using a triple quadrupole analyzer
      and operated in the multiple reaction monitoring mode.

PMID- 22627777
TI  - Acute alcohol intoxication and suicide: a gender-stratified analysis of the
      National Violent Death Reporting System.
AB  - OBJECTIVES: Although it is well known that people with alcohol dependence are at
      a markedly elevated risk for suicide, much less is known about the role of acute
      alcohol use in suicidal behaviours. The primary aims of this epidemiological
      study were to assess the prevalence and factors associated with acute alcohol
      intoxication among 57 813 suicide decedents in 16 states. METHODS: Data from the
      restricted National Violent Death Reporting System 2003-2009 for male and female
      suicide decedents aged 18 years and older were analysed by multiple logistic
      regression to compare decedents with and without acute alcohol intoxication
      (defined as blood alcohol concentration (BAC) >=0.08 g/dl). RESULTS: Among men,
      those who were younger, American Indian/Alaska Native, Hispanic, veterans, of
      lower educational attainment, deceased from a self-inflicted firearm injury or
      hanging/suffocation and residing in rural areas were more likely to have been
      intoxicated at the time of death. Among women, the factors associated with a BAC
      >=0.08 g/dl were younger age, being American Indian/Alaska Native, and using a
      firearm, hanging/suffocation or falling as method of death. CONCLUSIONS: In both
      men and women, alcohol intoxication was associated with violent methods of
      suicide and declined markedly with age, suggesting that addressing risks
      associated with acute alcohol use may be of the greatest aid in the prevention of
      violent suicides among young and middle age adults.

PMID- 22627778
TI  - DIAL: a randomised trial of a telephone brief intervention for alcohol.
AB  - BACKGROUND: Decreasing Injuries from ALcohol (DIAL) is a randomised control trial
      of a telephone brief intervention (BI) with injured emergency department (ED)
      patients with high-risk alcohol use. Here the authors examine 12-month outcomes
      of the intervention's effect on alcohol use, alcohol-related injuries and alcohol
      related negative consequences. METHODS: ED research assistants recruited adult
      injured patients who screened positive for high-risk alcohol use and were to be
      discharged home. After discharge, all participants received by telephone an
      assessment of their alcohol use, alcohol-related injuries, and alcohol-related
      negative consequences and then were randomised to treatment or standard care.
      Treatment consisted of two telephone sessions of BI focusing on risky alcohol
      use. Both groups were reassessed after 12 months. RESULTS: At 12 months, 249
      (89%) participants completed follow-up assessments. After using a log
      transformation, the difference in alcohol-related injuries between baseline and
      12-month follow-up was greater in the BI group than the standard care group
      (p=0.04); this is an effect size of Cohen's d=0.21. No difference between groups
      was found when comparing change in alcohol consumption and other alcohol-related
      negative consequences at 12 months. CONCLUSIONS: These findings suggest that a
      telephone BI with injured ED patients may decrease alcohol-related injuries.
      Identifying patients with risky alcohol use in the ED and then subsequently
      delivering the intervention by telephone after discharge has promise as a model
      for BI and deserves further study.

PMID- 22627779
TI  - Are there differences in injury mortality among refugees and immigrants compared
      with native-born?
AB  - BACKGROUND: The authors studied injury mortality in Denmark among refugees and
      immigrants compared with that among native Danes. METHOD: A register-based,
      historical prospective cohort design. All refugees (n=29, 139) and family
      reunited immigrants (n=27, 134) who between 1 January 1993 and 31 December 1999
      received residence permission were included and matched 1:4 on age and sex with
      native Danes. Civil registration numbers were cross-linked to the Register of
      Causes of Death, and fatalities due to unintentional and intentional injuries
      were identified based on ICD-10 diagnosis. Sex-specific mortality ratios were
      estimated by migrant status and region of birth, adjusting for age and income and
      using a Cox regression model after a median follow-up of 11-12 years. RESULTS:
      Compared with native Danes, both female (RR=0.44; 95% CI 0.23 to 0.83) and male
      (RR=0.40; 95% CI 0.29 to 0.56) refugees as well as female (RR=0.40; 95% CI 0.21
      to 0.76) and male (RR=0.22; 95% CI 0.12 to 0.42) immigrants had significantly
      lower mortality from unintentional injuries. Suicide rates were significantly
      lower for male refugees (RR=0.38; 95% CI 0.24 to 0.61) and male immigrants
      (RR=0.24; 95% CI 0.10 to 0.59), whereas their female counterparts showed no
      significant differences. Only immigrant women had a significantly higher homicide
      rate (RR=3.09; 95% CI 1.11 to 8.60) compared with native Danes. CONCLUSIONS:
      Overall results were advantageous to migrant groups. Research efforts should
      concentrate on investigating protective factors among migrants, which may benefit
      injury prevention in the majority population.

PMID- 22627780
TI  - Injury control training in the USA: meeting the challenge.

PMID- 22627781
TI  - Healthcare cost usage for hospitalised injuries sustained in industrial settings
      in the USA.
AB  - OBJECTIVE: To describe characteristics and outcomes of patients hospitalised for
      injuries occurring in industrial settings during a 1-year period. METHODS: A
      retrospective analysis of hospital admissions in the USA in 2006 using the
      Nationwide Inpatient Sample was performed. The International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9 CM) code E849.3
      (industrial place and premises) was used to identify work-related injury
      admissions. RESULTS: A total of 5826 patients were hospitalised with injuries
      sustained in industrial settings (weighted, 28,354 patients). The mean age was
      42.9 years (82% were men). They were 48% Caucasian, 19% Hispanic and 6% African
      American. The majority were admitted from the Emergency Department (72%). Further
      the majority of admissions were discharged home (79%; 9% with home healthcare)
      and 10.7% were transferred to another facility. The mean length of stay was 4.5
      days (range 0-109 days). Mean total charges per admission was US$32,254 (median
      US$18,364, 90th percentile US$66,607). Common diagnoses included: orthopaedic
      injuries (including amputations) to: finger/hand (20.9%), foot/ankle (8.2%), leg
      (10.2%) and spine (8.4%); infection (10.8%), pulmonary diagnosis (6.6%), soft
      tissue injuries (3.6%) and burns to <10% of the body (3.6%). Comorbidities
      included hypertension (17.0%) and diabetes mellitus (6.3%). Most common
      procedures performed included fracture reduction (17.6%), blood transfusions
      (3.1%) and spinal surgery (3%). A total of 194 (0.7%) patients died in the
      hospital. CONCLUSIONS: Injuries in industrial settings result in significant
      healthcare usage, morbidity and mortality on an annual basis in the USA. These
      admission levels facilitate development of targeted strategies to optimise the
      quality and economics of care for injuries in industrial settings.

PMID- 22627782
TI  - Active transportation to school in Canadian youth: should injury be a concern?
AB  - Active transportation to school provides a means for youth to incorporate
      physical activity into their daily routines, and this has obvious benefits for
      child health. Studies of active transportation have rarely focused on the
      negative health effects in terms of injury. This cross-sectional study is based
      on the 2009/10 Canadian Health Behaviour in School-Aged Children survey. A sample
      of children aged 11-15 years (n=20 076) was studied. Multi-level logistic
      regression was used to examine associations between walking or bicycling to
      school and related injury. Regular active transportation to school at larger
      distances (approximately >1.6 km; 1.0 miles) was associated with higher relative
      odds of active transportation injury (OR: 1.52; 95% CI 1.08 to 2.15), with a
      suggestion of a dose-response relationship between longer travel distances and
      injury (p=0.02). Physical activity interventions for youth should encourage
      participation in active transportation to school, while also recognising the
      potential for unintentional injury.

PMID- 22627784
TI  - The mammalian secreted RNases: mechanisms of action in host defence.
AB  - The mammalian ribonucleaseA family comprises a large group of structurally
      similar proteins which are secreted by a range of tissues and immune cells. Their
      physiological role is unclear. It has been suggested that some of these RNases
      contribute to host defence, notably eosinophil-derived neurotoxin, eosinophil
      cationic protein, eosinophil-associated RNases, RNase4, angiogenin (RNase5),
      RNase7, RNase8 and bovine seminal RNase. This review summarises data supporting
      the involvement of these proteins in host defence, focusing on their
      antimicrobial, cytotoxic and immunomodulatory activities. The extent to which the
      data support possible mechanisms of action for these proteins is discussed. This
      compilation of findings and current hypotheses on the physiological role of these
      RNases will provide a stimulus for further research and development of ideas on
      the contribution of the RNases to host defence.

PMID- 22627786
TI  - Rhenium complexes bearing phosphole-pyridine chelates: simple molecules with
      large chiroptical properties.
AB  - The synthesis and chiroptical properties of chiral rhenium complexes bearing mono
      or di-topic phosphole ligands are described.

PMID- 22627785
TI  - Classically or alternatively activated bovine monocyte-derived macrophages in
      vitro do not resemble CD163/Calprotectin biased macrophage populations in the
      teat.
AB  - The functional phenotype of resident macrophages significantly determines the
      character of an inflammatory response. In this study we identified two phenotypes
      of tissue macrophages in bovine teat tissue based on expression of Calprotectin
      and CD163. To investigate a possible link between the dichotomy in phenotype and
      functional properties of cells in association with different host mediators we
      set up an in vitro model with bovine monocyte-derived macrophages (MdM). In vitro
      differentiated MdM invariably and uniformly expressed both antigens. Classically
      activated MdM (IFN-gamma priming and LPS stimulation) showed a decreased CD163
      expression while alternative activation (IL-4/IL-13 priming) did not change
      expression of CD163 and Calprotectin. Differently activated MdM showed a clearly
      distinct expression of genes related to classical (IL-12, inducible NO synthase)
      or alternative activation (IL-10, arginase I). The presence of the inflammatory
      host mediator prostaglandin E(2) (PGE(2)) neither influenced expression of
      Calprotectin and CD163 nor gene expression profiles in MdM generated in the
      presence of PGE(2) (PGE(2)-MdM). Supernatants of PGE(2-)MdM, however,
      significantly dampened the migration of neutrophilic granulocytes. The results of
      this study highlight the discrepancy between in vivo and in vitro obtained
      macrophages and point to the necessity to analyze the functional capacities of
      bovine tissue macrophages in situ.

PMID- 22627787
TI  - Paradoxical cryptococcal immune reconstitution inflammatory syndrome in advanced
      chronic kidney disease.
AB  - Cryptococcal-related immune reconstitution inflammatory syndrome (IRIS) is
      frequently seen in immunocompromised patients. A 45-year-old man with advanced
      chronic kidney disease (CKD) received intensive antifungal treatment for
      pulmonary cryptococcosis. Despite negative pleural effusion cultures and
      declining serum cryptococcal antigen titers, the patient presented with
      progressive pulmonary infiltration, intermittent fever, and elevated C-reactive
      protein. Steroids were given for suspected IRIS, and the clinical condition
      improved dramatically. This is the first report on paradoxical cryptococcal IRIS
      in a patient with advanced CKD. 

PMID- 22627788
TI  - Three weeks of erythropoietin treatment hampers skeletal muscle mitochondrial
      biogenesis in rats.
AB  - The blood O(2)-carrying capacity is maintained by the O(2)-regulated production
      of erythropoietin (Epo), which stimulates the proliferation and survival of red
      blood cell progenitors. Epo has been thought to act exclusively on erythroid
      progenitor cells. However, recent studies have identified the erythropoietin
      receptor (EpoR) in other cells, such as neurons, astrocytes, microglia, heart,
      cancer cell lines, and skeletal muscle provides evidence for a potential role of
      Epo in other tissues. In this study we aimed to determine the effect of
      recombinant human erythropoietin (rHuEpo) on skeletal muscle adaptations such as
      mitochondrial biogenesis, myogenesis, and angiogenesis in different muscle fibre
      types. Fourteen male Wistar rats were randomly divided into two experimental
      groups, and saline or rHuEpo (300 IU) was administered subcutaneously three times
      a week for 3 weeks. We evaluated the protein expression of intermediates involved
      in the mitochondrial biogenesis cascade, the myogenic cascade, and in
      angiogenesis in the oxidative soleus muscle and in the glycolytic gastrocnemius
      muscle. Contrary to our expectations, rHuEpo significantly hampered the
      mitochondrial biogenesis pathway in gastrocnemius muscle (PGC-1alpha, mTFA and
      cytochrome c). We did not find any effect of the treatment on cellular signals of
      myogenesis (MyoD and Myf5) or angiogenesis (VEGF) in either soleus or
      gastrocnemius muscles. Finally, we found no significant effect on the maximal
      aerobic velocity at the end of the experiment in the rHuEpo-treated animals. Our
      findings suggest that 3 weeks of rHuEpo treatment, which generates an increase of
      oxygen carrying capacity, can affect mitochondrial biogenesis in a muscle fibre
      specific dependent manner.

PMID- 22627789
TI  - The young and the reckless.

PMID- 22627790
TI  - Preso1, mGluR5 and the machinery of pain.

PMID- 22627791
TI  - Reward and punishment illuminated.

PMID- 22627792
TI  - Squaring cortex with color.

PMID- 22627793
TI  - The best of times, the worst of times for psychiatric disease.

PMID- 22627794
TI  - MR imaging-based correction for partial volume effect improves detectability of
      intractable epileptogenic foci on iodine 123 iomazenil brain SPECT images: an
      extended study with a larger sample size.
AB  - BACKGROUND AND PURPOSE: It has been suggested, on the basis of a previous pilot
      study conducted in a small number of patients, that MR imaging-based PVE
      correction in I-123 iomazenil brain SPECT improves the detectability of cortical
      epileptogenic foci. In the present study, we performed an investigation by using
      a larger sample size to establish the effectiveness of the PVE correction and to
      conduct a detailed evaluation based on the histologic classification of lesions.
      MATERIALS AND METHODS: Seventy-five patients (male/female, 37/38; age, 28 +/- 12
      years) with intractable epilepsy who had undergone surgical treatment were
      enrolled in this study. I-123 iomazenil SPECT and MR imaging examinations were
      performed before the operation in all patients. I-123 iomazenil SPECT images with
      and without MR imaging-based PVE correction were assessed visually and by
      semiquantitative analysis based on the AI(%) of the SPECT count in the resected
      lesions. RESULTS: The sensitivity, specificity, and accuracy of foci detection by
      visual assessment were significantly higher after PVE correction compared with
      the values obtained before the correction. The results of the semiquantitative
      analysis revealed that the asymmetry of the SPECT counts was significantly
      increased after the PVE correction in the surgically resected lesions in cases of
      mesial temporal sclerosis, tumor, and malformations of cortical development.
      CONCLUSIONS: The effectiveness of MR imaging-based PVE correction in I-123
      iomazenil brain SPECT in improving the detection of cortical epileptogenic foci
      with abnormal histologic findings was established by our investigation conducted
      on a large sample size.

PMID- 22627795
TI  - Clinical stroke penumbra: use of National Institutes of Health stroke scale as a
      surrogate for CT perfusion in patient triage for intra-arterial middle cerebral
      artery stroke therapy.
AB  - BACKGROUND AND PURPOSE: CTP may help triage acute stroke patients for IAT, but
      requires additional contrast agent, radiation, and imaging time. Our aim was to
      determine whether clinical examination (NIHSS) with NCCT and CTA can substitute
      for CTP without significantly affecting IAT triage of patients with acute MCA
      stroke. MATERIALS AND METHODS: We reviewed NCCT, CTA, and CTP imaging performed
      within 8 hours of symptom onset in 36 patients presenting with MCA territory
      stroke (September 2007-October 2009). Two neuroradiologists reviewed,
      independently and by consensus, NCCT, CTA, and CTP (CTP group), and 2 different
      neuroradiologists blinded to CTP reviewed NCCT, CTA, and NIHSS (stroke scale
      group) to determine IAT eligibility: M1 or proximal M2 occlusion; infarct core
      <1/3 MCA territory; and ischemic penumbra >20% infarct core. The stroke scale
      group estimated infarct core from NCCT and CTA source images and ischemic
      penumbra from core size relative to NIHSS score and re-evaluated patients after
      unblinding to CTP. We computed intragroup and intergroup kappa scores for IAT
      treatment recommendation and used the McNemar test to determine whether CTP
      significantly affected the stroke scale group's decisions. RESULTS: IAT was
      recommended in 16/36 (44%) and 17/36 (47%) patients by the CTP and stroke scale
      groups, respectively, with intragroup kappa scores of 0.78 +/- 0.11 versus 0.83
      +/- 0.09. The intergroup kappa score was 0.83 +/- 0.09. When unblinded to CTP,
      the stroke scale group revised 2/36 (5.6%) decisions, which was insignificant (P
      = .48, McNemar test). CONCLUSIONS: NIHSS interpreted with NCCT and CTA may be an
      effective substitute for CTP-derived measures in the IAT triage of patients with
      acute MCA stroke. Replacing CTP may potentially reduce radiation and contrast
      dose and time to treatment.

PMID- 22627796
TI  - The use of adaptive statistical iterative reconstruction in pediatric head CT: a
      feasibility study.
AB  - BACKGROUND AND PURPOSE: Iterative reconstruction techniques facilitate CT dose
      reduction; though to our knowledge, no group has explored using iterative
      reconstruction with pediatric head CT. Our purpose was to perform a feasibility
      study to assess the use of ASIR in a small group of pediatric patients undergoing
      head CT. MATERIALS AND METHODS: An Alderson-Rando head phantom was scanned at
      decreasing 10% mA intervals relative to our standard protocol, and each study was
      then reconstructed at 10% ASIR intervals. An intracranial region of interest was
      consistently placed to estimate noise. Our ventriculoperitoneal shunt CT protocol
      was subsequently modified, and patients were scanned at 20% ASIR with
      approximately 20% mA reductions. ASIR studies were anonymously compared with
      older non-ASIR studies from the same patients by 2 attending pediatric
      neuroradiologists for diagnostic utility, sharpness, noise, and artifacts.
      RESULTS: The phantom study demonstrated similar noise at 100% mA/0% ASIR (3.9)
      and 80% mA/20% ASIR (3.7). Twelve pediatric patients were scanned at reduced dose
      at 20% ASIR. The average CTDI(vol) and DLP values of the 20% ASIR studies were
      22.4 mGy and 338.4 mGy-cm, and for the non-ASIR studies, they were 28.8 mGy and
      444.5 mGy-cm, representing statistically significant decreases in the CTDI(vol)
      (22.1%, P = .00007) and DLP (23.9%, P = .0005) values. There were no significant
      differences between the ASIR studies and non-ASIR studies with respect to
      diagnostic acceptability, sharpness, noise, or artifacts. CONCLUSIONS: Our
      findings suggest that 20% ASIR can provide approximately 22% dose reduction in
      pediatric head CT without affecting image quality.

PMID- 22627797
TI  - Comparison of carotid plaque ulcer detection using contrast-enhanced and time-of
      flight MRA techniques.
AB  - BACKGROUND AND PURPOSE: Ulceration in carotid plaque is a risk indicator for
      ischemic stroke. Our aim was to compare plaque ulcer detection by standard TOF
      and CE-MRA techniques and to identify factors that influence its detection.
      MATERIALS AND METHODS: Carotid MR imaging scans were acquired on 2066
      participants in the ARIC study. We studied the 600 thickest plaques. TOF-MRA, CE
      MRA, and black-blood MR images were analyzed together to define ulcer presence
      (plaque surface niche >=2 mm in depth). Sixty ulcerated arteries were detected.
      These arteries were randomly assigned, along with 40 nonulcerated plaques from
      the remaining 540, for evaluation of ulcer presence by 2 neuroradiologists.
      Associations between ulcer detection and ulcer characteristics, including
      orientation, location, and size, were determined and explored by CFD modeling.
      RESULTS: One CE-MRA and 3 TOF-MRAs were noninterpretable and excluded. Of 71
      ulcers in 56 arteries, readers detected an average of 39 (55%) on both TOF-MRA
      and CE-MRA, 26.5 (37.5%) only on CE-MRA, and 1 (1.5%) only on TOF-MRA, missing
      4.5 (6%) ulcers by both methods. Ulcer detection by TOF-MRA was associated with
      its orientation (distally pointing versus perpendicular: OR = 5.57 [95% CI, 1.08
      28.65]; proximally pointing versus perpendicular: OR = 0.21 [95% CI, 0.14-0.29]);
      location relative to point of maximum stenosis (distal versus isolevel: OR = 5.17
      [95% CI, 2.10-12.70]); and neck-to-depth ratio (OR = 1.96 [95% CI, 1.11-3.45])
      after controlling for stenosis and ulcer volume. CONCLUSIONS: CE-MRA detects more
      ulcers than TOF-MRA in carotid plaques. Missed ulcers on TOF-MRA are influenced
      by ulcer orientation, location relative to point of maximum stenosis, and neck-to
      depth ratio.

PMID- 22627798
TI  - Diagnostic yield of fluoroscopy-guided biopsy for infectious spondylitis.
AB  - BACKGROUND AND PURPOSE: CT is currently the method of choice for guiding biopsy
      of lesions of the spine. However, in our hospital, fluoroscopy-guided
      percutaneous biopsy has been preferred for several years because of equipment
      availability and easy craniocaudal angulation. The aim of this study was to
      evaluate the efficacy of fluoroscopy-guided percutaneous biopsy in a clinical
      setting for diagnosing infectious spondylitis. MATERIALS AND METHODS: A
      retrospective study was performed to evaluate 170 fluoroscopy-guided percutaneous
      biopsies in 140 patients (male/female = 70:70; mean age, 65.1 years; range, 16-89
      years) in a clinical setting who were suspected of having infectious spondylitis
      between July 2003 and March 2010. Diagnosis was based on pathologic confirmation
      by tissue or culture from biopsy. The percentage of adequate specimens for
      diagnosis, histopathologic diagnosis for infectious spondylitis, and positive
      cultures for causative organisms were evaluated by retrospective review of
      medical records. RESULTS: Adequate specimens for diagnosis were obtained in 165
      of 170 cases (97.1%). The diagnosis of infectious spondylitis resulted in 134 of
      170 cases confirmed through histopathology or clinical outcome (78.8%). In 51 of
      134 cases (38.1%), the causative organism was confirmed by specimens from
      percutaneous bone biopsy. There were no biopsy-related major complications. The
      most common organism isolated was Mycobacterium tuberculosis (24 cases), followed
      by Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus viridans.
      CONCLUSIONS: Fluoroscopy-guided percutaneous biopsy is as accurate and effective
      as CT-guided biopsy for diagnosing infectious spondylitis.

PMID- 22627799
TI  - Association between carotid artery plaque type and cerebral microbleeds.
AB  - BACKGROUND AND PURPOSE: CMBs have become increasingly recognized with the
      widespread use of MR imaging techniques that are sensitive to iron deposits. The
      purpose of this study was to correlate the presence of CMBs and carotid plaque
      characteristics. MATERIAL AND METHODS: Seventy consecutive patients (47 men; 23
      women; mean age, 65 years) were prospectively analyzed. Carotid arteries were
      studied using a 16-detector row CT scanner, whereas the brain was explored with
      an MR imaging 1.5T system. CMBs were studied using a T2*-weighted GRE sequence.
      CMBs were classified by an ordinal scale and carotid plaques were characterized
      based on their composition as fatty, mixed, or calcified. Patients were
      classified as symptomatic and asymptomatic. Chi-square and multiple logistic
      regression analyses, as well as ROCs, were calculated. RESULTS: The prevalence of
      CMBs was 30%. A statistically significant difference in CMB prevalence was
      observed between symptomatic (46%) and asymptomatic (19%) patients (P value =
      .0021; OR = 3.7). Correlation analysis demonstrated an association between the
      number of CMBs and the symptoms (P = .0001). A statistically significant
      association was observed between the presence of fatty plaque and CMBs (P =
      .0019). CONCLUSIONS: The results of this study suggest an association between the
      presence of carotid artery fatty plaque, symptoms, and CMBs. Moreover, we found
      that the presence (and entity) of CMBs may represent an indicator of
      cerebrovascular symptom severity.

PMID- 22627800
TI  - Retinoblastoma: value of dynamic contrast-enhanced MR imaging and correlation
      with tumor angiogenesis.
AB  - BACKGROUND AND PURPOSE: Noninvasive evaluation of retinoblastoma treatment
      response has become more important due to increased use of eye-sparing
      treatments. We evaluated the relation between DCE-MR imaging and histopathologic
      parameters to determine the value of DCE-MR imaging in assessing tumor
      angiogenesis and prognostic features. MATERIALS AND METHODS: Fifteen consecutive
      patients with retinoblastoma (mean age, 24 months; range, 2-70 months) undergoing
      enucleation as the primary treatment (15 eyes) were scanned at 1.5T by using
      dedicated surface coils. Pretreatment DCE-MR imaging of the most affected eye was
      evaluated by 2 observers by using curve-pattern analysis, with the first 5
      minutes of each curve and the full time-series described as kappa(5min) and
      kappa(17min), respectively. Assessed histopathologic and immunologic parameters
      included optic nerve invasion, choroid invasion, MVD, tumor necrosis, and
      expression of VEGF and Flt-1. RESULTS: The median value of kappa(5min) was 1.28
      (range, 0.87-2.07) and correlated positively with MVD (P = .008). The median
      value of kappa(17min) was 1.33 (range, 0.35-3.08) and correlated negatively with
      tumor necrosis (P = .002). Other histopathologic and immunohistopathologic
      parameters did not correlate with DCE-MR imaging parameters. Interobserver
      agreement was 0.53 for kappa(5min) and 0.91 for kappa(17min). CONCLUSIONS: In
      retinoblastoma, the early phase of the DCE time curve positively correlates with
      MVD, while the presence of late enhancement is correlated with necrosis. Thus,
      the potential for DCE-MR imaging to noninvasively assess tumor angiogenesis and
      necrosis in retinoblastoma is promising and warrants further investigation.

PMID- 22627801
TI  - Back to the tower of babel: comparing outcomes from aneurysm trials.

PMID- 22627802
TI  - C-arm CT measurement of cerebral blood volume using intra-arterial injection of
      contrast medium: an experimental study in canines.
AB  - BACKGROUND AND PURPOSE: Measurement of perfusion parameters is typically done
      using an intravenous injection of contrast medium. This purpose of this study was
      to evaluate the feasibility of measuring regional and global CBV using C-arm CT
      with IA injections of contrast medium. MATERIALS AND METHODS: Twelve canines were
      studied. CBV measurement was performed using standard PCT, and then using C-arm
      CT with IV and IA contrast. Values obtained using C-arm CT were compared with
      those using PCT. RESULTS: C-arm CT CBV maps using IA injections required less
      contrast than ones with IV injections. PCT and C-arm CT using IV and AA
      injections provided comparable maps. In controls, C-arm CT with a CCA or VA
      injection provided comparable maps to PCT. In animals with a stroke, a CCA or VA
      injection did not provide maps comparable to ones made with PCT. IV and AA C-arm
      CT showed excellent quantitative agreement with PCT, while CCA and VA C-arm CT
      studies did not. CONCLUSIONS: Measurement of global CBV using C-arm CT in
      conjunction with either an IV or an AA injection was feasible in controls and
      dogs with a stroke. Measurement of regional CBV with C-arm CT using either CCA or
      VA injection, in normal canines, provided CBV maps qualitatively comparable with
      those obtained with PCT; the absolute CBV values from these maps were in poor
      agreement with PCT measurements. Valid measurement of CBV using C-arm CT requires
      all tissue in a target region to be fully and equally opacified during any
      acquisition. Using CCA or VA injections, it was impossible to document if and
      when this had been achieved. CBV measurements using these routes of injection
      were therefore not reliable.

PMID- 22627803
TI  - Improved arterial visualization in cerebral CT perfusion-derived arteriograms
      compared with standard CT angiography: a visual assessment study.
AB  - BACKGROUND AND PURPOSE: Invasive cerebral DSA has largely been replaced by CTA,
      which is noninvasive but has a compromised arterial view due to superimposed bone
      and veins. The purpose of this study was to evaluate whether arterial
      visualization in CTPa is superior to standard CTA, which would eliminate the need
      for an additional CTA scan to assess arterial diseases and therefore reduce
      radiation dose. MATERIALS AND METHODS: In this study, we included 24 patients
      with subarachnoid hemorrhage for whom CTA and CTP were available. Arterial
      quality and presence of superimposed veins and bone in CTPa were compared with
      CTA and scored by 2 radiologists by using a VAS (0%-100%). Average VAS scores
      were determined and VAS scores per patient were converted to a 10-point NRS.
      Arterial visualization was considered to be improved when the highest rate (NRS
      10, VAS > 90%) was scored for arterial quality, and the lowest rate (NRS 1, VAS <
      10%), for the presence of superimposed veins and bone. A sign test with
      continuity correction was used to test whether the number of cases with these
      rates was significant. RESULTS: Average VAS scores in the proximal area were 94%
      (arterial quality), 4% (presence of bone), and 7% (presence of veins). In this
      area, the sign test showed that a significant number of cases scored NRS 10 for
      arterial quality (P < .02) and NRS 1 for the presence of superimposed veins and
      bone (P < .01). CONCLUSIONS: Cerebral CTPa shows improved arterial visualization
      in the proximal area compared with CTA, with similar arterial quality but no
      superimposed bone and veins.

PMID- 22627804
TI  - Further examination of diagnostic performance in the context of a fellows'
      journal club article.

PMID- 22627805
TI  - Improving piezoelectric cell printing accuracy and reliability through neutral
      buoyancy of suspensions.
AB  - The sedimentation and aggregation of cells within inkjet printing systems has
      been hypothesized to negatively impact printer performance. The purpose of this
      study was to investigate this influence through the use of neutral buoyancy.
      Ficoll PM400 was used to create neutrally buoyant MCF-7 breast cancer cell
      suspensions, which were ejected using a piezoelectric drop-on-demand inkjet
      printing system. It was found that using a neutrally buoyant suspension greatly
      increased the reproducibility of consistent cell counts, and eliminated nozzle
      clogging. Moreover, the use of Ficoll PM400 was shown to not affect cellular
      viability. This is the first demonstration of such scale and accuracy achieved
      using a piezoelectric inkjet printing system for cellular dispensing.

PMID- 22627806
TI  - Different recognition cues reveal the decision rules used for egg rejection by
      hosts of a variably mimetic avian brood parasite.
AB  - Brood parasitism imposes several fitness costs on the host species. To reduce
      these costs, hosts of avian brood parasites have evolved various defenses, of
      which egg rejection is the most prevalent. In the face of variable host-parasite
      mimicry and the costs of egg discrimination itself, many hosts reject only some
      foreign eggs. Here, we experimentally varied the recognition cues to study the
      underlying cognitive mechanisms used by the Chalk-browed Mockingbird (Mimus
      saturninus) to reject the white immaculate eggs laid by the parasitic Shiny
      Cowbird (Molothrus bonariensis). Immaculate eggs are the only parasite eggs
      rejected by this host, as it accepts all polymorphic, spotted eggs laid by
      cowbirds. Using a within-breeding pair experimental design, we tested for the
      salience of spotting, UV reflectance, and brightness in eliciting rejection. We
      found that the presence of spotting significantly decreased the probability of
      rejection while increments in brightness significantly increased rejection
      frequencies. The cognitive rules underlying mockingbird rejection behavior can be
      explained by a decision-making model which predicts changes in the levels of
      rejection in direct relation to the number of relevant attributes shared between
      host and parasite eggs.

PMID- 22627807
TI  - Naturally occurring, physiologically normal, primate chimeras.
AB  - Callitrichids, South American primates including marmosets and tamarins, have
      evolved a unique physiology. Twins share a placenta during gestation and exchange
      stem cells, resulting in naturally occurring chimeric adults. Our study used a
      quantitative PCR-based assay to address whether this chimerism was restricted to
      blood and other cells of the hematopoietic lineage or whether it extended to
      other somatic tissues. These studies help to characterize species that have
      adapted evolutionarily to pervasive chimerism, with every individual healthy and
      unperturbed. This experiment of evolution offers insight into transplantation and
      histocompatibility, reproductive biology and behavior, and innate and adaptive
      immunity.

PMID- 22627808
TI  - A functional comparison between the HER2(high)/HER3 and the HER2(low)/HER3 dimers
      on heregulin-beta1-induced MMP-1 and MMP-9 expression in breast cancer cells.
AB  - Overexpression of HER2 correlates with more aggressive tumors and increased
      resistance to cancer chemotherapy. However, a functional comparison between the
      HER2(high)/HER3 and the HER2(low)/HER3 dimers on tumor metastasis has not been
      conducted. Herein we examined the regulation mechanism of heregulin- beta1 (HRG)
      induced MMP-1 and -9 expression in breast cancer cell lines. Our results showed
      that the basal levels of MMP-1 and -9 mRNA and protein expression were increased
      by HRG treatment. In addition, HRG-induced MMP-1 and -9 expression was
      significantly decreased by MEK1/2 inhibitor, U0126 but not by
      phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294002. To confirm the role of
      MEK/ERK pathway on HRG-induced MMP-1 and -9 expression, MCF7 cells were
      transfected with constitutively active adenoviral- MEK (CA-MEK). The level of MMP
      1 and -9 expressions was increased by CA-MEK. MMP-1 and -9 mRNA and protein
      expressions in response to HRG were higher in HER2 overexpressed cells than in
      vector alone. The phosphorylation of HER2, HER3, ERK, Akt, and JNK were also
      significantly increased in HER2 overexpressed MCF7 cells compared with vector
      alone. HRG-induced MMP-1 and -9 expressions were significantly decreased by
      lapatinib, which inhibits HER1 and HER2 activity, in both vector alone and HER2
      overexpressed MCF7 cells. Finally, HRG-induced MMP-1 and MMP-9 expression was
      decreased by HER3 siRNA overexpression. Taken together, we suggested that HRG
      induced MMP-1 and MMP-9 expression is mediated through HER3 dependent pathway and
      highly expressed HER2 may be associated with more aggressive metastasis than the
      low expressed HER2 in breast cancer cells.

PMID- 22627810
TI  - Bored to sleep.

PMID- 22627809
TI  - Synergistic induction of cancer cell migration regulated by Gbetagamma and
      phosphatidylinositol 3-kinase.
AB  - Phosphatidylinositol 3-kinase (PI3K) is essential for both G protein-coupled
      receptor (GPCR)- and receptor tyrosine kinase (RTK)-mediated cancer cell
      migration. Here, we have shown that maximum migration is achieved by full
      activation of phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1
      (P-Rex1) in the presence of Gbetagamma and PI3K signaling pathways.
      Lysophosphatidic acid (LPA)- induced migration was higher than that of epidermal
      growth factor (EGF)-induced migration; however, LPA-induced activation of Akt was
      lower than that stimulated by EGF. LPA-induced migration was partially blocked by
      either Gbetagamma or RTK inhibitor and completely blocked by both inhibitors. LPA
      induced migration was synergistically increased in the presence of EGF and vice
      versa. In correlation with these results, sphingosine-1-phosphate (S1P)-induced
      migration was also synergistically induced in the presence of insulin-like growth
      factor-1 (IGF-1). Finally, silencing of P-Rex1 abolished the synergism in
      migration as well as in Rac activation. Moreover, synergistic activation of MMP-2
      and cancer cell invasion was attenuated by silencing of P-Rex1. Given these
      results, we suggest that P-Rex1 requires both Gbetagamma and PI3K signaling
      pathways for synergistic activation of Rac, thereby inducing maximum cancer cell
      migration and invasion.

PMID- 22627815
TI  - Ensuring successful preceptorships for nursing students.

PMID- 22627816
TI  - Best practices in postoperative feeding.

PMID- 22627818
TI  - Managing fatigue in patients with multiple sclerosis.

PMID- 22627820
TI  - Patient Education Series. Nonmelanoma skin cancers.

PMID- 22627822
TI  - Many shades of gray.

PMID- 22627823
TI  - Mitochondrial diseases: Problems in the power plant.

PMID- 22627824
TI  - Direct care nurses transitioning to clinical faculty.

PMID- 22627825
TI  - Nurses and body art: What's your perception?

PMID- 22627826
TI  - Caring for patients in any language: Does it matter?

PMID- 22627827
TI  - Hydrocephalus after cerebral injury.

PMID- 22627828
TI  - Recognizing and preventing norovirus infection.

PMID- 22627830
TI  - Hydrofluoric acid skin exposure.

PMID- 22627831
TI  - Analytical challenges and technical limitations in assessing circulating miRNAs.
AB  - MiRNAs are emerging as promising biomarkers in cardiovascular diseases and may
      constitute a novel mechanism of intercellular communication. Accurate
      quantification of circulating miRNAs is essential. A variety of technological
      approaches and platforms have been developed with increased sensitivity and
      specificity for the detection and quantification of circulating miRNAs. In this
      review, we focus on the technical aspects and discuss the analytical challenges
      in profiling circulating miRNAs.

PMID- 22627832
TI  - Bevacizumab-induced perforation of the gastrointestinal tract: clinical and
      radiographic findings in 11 patients.
AB  - AIM: To present the gastrointestinal (GI) complications associated with
      bevacizumab therapy and their findings on abdominal imaging studies. METHODS: A
      computerized search identified 11 patients with GI complications of bevacizumab
      therapy on abdominal CT (n = 11) and fluoroscopic GI contrast studies (n = 4) who
      met our study criteria (including five patients with ovarian cancer, five with
      colon cancer, and one with cervical cancer). The medical records and imaging
      studies were reviewed to determine the clinical and radiographic findings in
      these patients. RESULTS: All 11 patients had findings of GI perforation on CT, or
      CT and GI contrast studies. CT revealed a localized extraluminal collection
      containing gas, fluid, and/or contrast material in eight patients (73%) with
      focal perforation, and free abdominal air and fluid in three (27%) with free
      perforation The imaging studies also revealed seven fistulas, including two
      colovaginal, one rectovaginal, one enterocutaneous, one colocutaneous, one
      gastrocolic, and one colorectal fistula. Eight (73%) of the 11 patients died
      within 1 year of the development of GI perforation, and the perforation was felt
      to be the cause of death in four patients (36%). CONCLUSION: Abdominal CT and
      fluoroscopic GI contrast studies are useful imaging tests for the diagnosis of
      potentially life-threatening GI perforation as a complication of bevacizumab
      therapy. When GI perforation is detected on abdominal imaging studies, treatment
      with bevacizumab should immediately be discontinued.

PMID- 22627833
TI  - A novel immunocompetent murine tumor model for the evaluation of RCAd-enhanced
      RDAd transduction efficacy.
AB  - Low gene transfer rate in tumors, high dose-induced acute inflammatory response,
      and lack of an immunocompetent preclinical animal model to accurately reflect the
      therapeutic efficacy are prominent reasons for the lack of clinical success of
      adenoviral (Ad) vectors. In this study, we tested whether human replication
      competent adenovirus (RCAd) can replicate in T739 mouse bladder transitional
      tumor cells (BTT) and lung adenocarcinoma cells (LA795), and whether RCAd can
      enhance the transduction rate and transgene expression of human replication
      defective adenoviruses (RDAd) in these tumor cells in vitro and in vivo. We
      demonstrated that human RCAd exhibited good infectability and cytopathologic
      effects in mouse BTT and LA795 cells, which was comparable to that in A549 and
      NCIH460 human tumor cells. In contrast, no infectability and cytopathologic
      effects were observed in other three mouse tumor cells such as 4T1, B16, and
      Lewis cells. The combined use of RCAd with RDAd significantly enhanced RDAd
      transduction efficiency in BTT and LA795 tumor cells in vitro and in vivo. When
      BTT and LA795 cells were co-infected with RDAd Ad-EGFP and RCAd, a large amount
      of E1a expression and 2-3 orders of increases in Ad-EGFP genomic DNA were
      observed. In contrast, the expression of the late gene Hexon is very low, which
      may explain ineffective packaging of viral particles. In conclusion, our study
      provided a novel immunocompetent animal model which is useful for evaluating RCAd
      infectability, cytopathy, and replication. The combined use of RCAd and RDAd
      provided a new solution for cancer gene therapy.

PMID- 22627840
TI  - Efficient catalytic cyclizations of three and two imine assemblies: direct access
      to tetrahydroimidazo[1,5-c]imidazol-7-ones and imidazoles.
AB  - A cascade cyclization involving union of three imines by an organocatalyst
      proline is established to afford new fused-tetrahydroimidazo[1,5-c]imidazol-7
      ones with excellent regio- and stereoselectivity. Another dehydrogenative
      cyclization by union of two imines is developed using the Cu(OTf)(2)-Ag(2)O combo
      catalyst to furnish functionalized imidazoles.

PMID- 22627834
TI  - RIN1 exhibits oncogenic property to suppress apoptosis and its aberrant
      accumulation associates with poor prognosis in melanoma.
AB  - Malignant melanoma is an increasing disease in China, and its molecular
      mechanisms of development and progression are limited. The objective of this
      study was to investigate the expression of Ras interaction/interference 1 (RIN1)
      protein and its clinical significance in human melanoma. Immunohistochemistry was
      performed to detect the expression of RIN1 in 81 melanoma patients with a 5-year
      follow-up. The prognosis of the patients, classified by the clinicopathologic
      features and RIN1 expression, was assessed by multivariate analysis. RIN1 levels
      were then analyzed with overall survival (OS), progression-free survival (PFS),
      and recurrence-free survival (RFS) in the cohort. The biological function was
      determined by proliferation assay, flow cytometry analysis through knocking down
      of RIN1 in melanoma cells A375, as well as caspase-3 activation and PARP cleavage
      were detected by western blot or fluorometric assay. Data showed that RIN1 was
      overexpressed in melanoma samples. High-level RIN1 expression was observed in
      49.4 % (40 of 81 cases), associated with thickness grade (P = 0.008) and lymph
      node metastasis (P < 0.001). Two distinguished subgroups were segregated by RIN1
      levels within this set comparing prognostication of OS, PFS, and RFS.
      Importantly, RIN1 level was revealed as the significant independent prognostic
      factor for death and progression but a weak contribution for recurrence.
      Moreover, knock down of RIN1 expression in A375 cells, suppressed cell
      proliferation and induced apoptosis through caspase-3 activation and PARP
      cleavage. RIN1 expression could be a potential prognostic predictor for the
      melanoma patients and provide a potential target therapy for melanoma treatment.

PMID- 22627844
TI  - Molecular simulation design of a multisite solid for the abatement of cold start
      emissions.
AB  - A highly effective hydrocarbon (HC) trap for the abatement of cold start HC
      emissions with specific adsorption sites for the different molecules present in
      the exhaust gases has been designed by means of molecular simulation tools, and
      later synthesized.

PMID- 22627845
TI  - Fetal microchimerism in skin wound healing.
AB  - Skin wound healing is a complex regenerative process involving various cell
      types. We recently investigated whether fetal microchimeric cells (FMCs) acquired
      during gestation contribute to maternal wound healing and used fetal
      microchimerism to investigate the recruitment of distant endothelial progenitor
      cells in skin wounds. Our study showed that fetal progenitor cells are recruited
      into maternal wounds and participate in inflammation and angiogenesis. These
      fetal cells might have beneficial effects in situations of maternal defective
      healing, and might also modify the adult maternal wound environment toward a
      scarless fetal-like wound healing.

PMID- 22627847
TI  - Inhibition of common cold-induced aggravation of childhood asthma by leukotriene
      receptor antagonists.
AB  - BACKGROUND: Virus infection is an important risk factor for aggravation of
      childhood asthma. The objective of this study was to examine the effect of drugs
      on aggravation of asthma induced by a common cold. METHODS: Asthma control was
      examined in a survey of 1,014 Japanese pediatric patients with bronchial asthma.
      The occurrence of common cold, asthma control, and drugs used for asthma control
      were investigated using a modified Childhood Asthma Control Test (C-ACT) for
      patients aged <4 years old and 4 to 11 years old, and an Asthma Control Test
      (ACT) for patients aged 12 to 15 years old. RESULTS: The status of asthma control
      did not differ among the age groups. The prevalence of common cold and
      aggravation of asthma were significantly higher in patients aged <4 years old.
      Control of asthma following common cold-induced aggravation was significantly
      less effective in patients aged <4 years old compared to those aged >=4 years
      old. In patients aged <4 years old with a common cold, asthma control was
      significantly more effective for those treated with leukotriene receptor
      antagonists (LTRAs) compared to treatment without LTRAs. Asthma control did not
      differ between patients who did or did not take inhaled corticosteroids or long
      acting beta2 stimulants. CONCLUSIONS: These findings showed a high prevalence of
      common cold in younger patients with childhood asthma and indicated that common
      cold can induce aggravation of asthma. LTRAs are useful for long-term asthma
      control in very young patients who develop an asthma attack due to a common cold.

PMID- 22627846
TI  - Superiority of nebulized corticosteroids over dry powder inhalers in certain
      patients with cough variant asthma or cough-predominant asthma.
AB  - BACKGROUND: The particle distribution might differ between nebulizer therapy and
      metered-dose inhaler (MDI) or dry powder inhaler (DPI) therapy because the
      particles repeatedly enter/re-enter the airways with the nebulizer. Inhaled
      corticosteroids (ICS) were administered with a nebulizer to assess the benefit of
      changes in the distribution of particles in patients with cough variant asthma
      (CVA) and cough-predominant asthma (CPA). METHODS: Patients whose symptoms were
      not controlled by their current therapy were enrolled. In patients receiving high
      dose ICS by MDI or DPI (ICS-MDI/DPI), steroid therapy was switched to
      1,320MUg/day of nebulized dexamethasone (1,600MUg as dexamethasone sodium
      phosphate) (chronic steroid-independent group). In patients receiving systemic
      steroids regardless of their ICS-MDI/DPI therapy, nebulized dexamethasone was
      added and any concurrent ICS-MDI/DPI therapy was halted to detect a steroid
      sparing effect (chronic steroid-dependent group). In patients with acute
      exacerbation of CVA or CPA and persistent symptoms despite systemic
      corticosteroids, nebulized dexamethasone was added to assess its effect (acute
      group). RESULTS: Superior symptom control was achieved in 10 out of 12 steroid
      independent patients, 3 out of 6 steroid-dependent patients, and all 7 acute
      patients. CONCLUSIONS: Delivery of ICS via a nebulizer has advantages over ICS
      MDI/DPI in some patients with CVA or CPA.

PMID- 22627848
TI  - Aspirin-intolerant asthma (AIA) assessment using the urinary biomarkers,
      leukotriene E4 (LTE4) and prostaglandin D2 (PGD2) metabolites.
AB  - The clinical syndrome of aspirin-intolerant asthma (AIA) is characterized by
      aspirin/nonsteroidal anti-inflammatory drug intolerance, bronchial asthma, and
      chronic rhinosinusitis with nasal polyposis. AIA reactions are evidently
      triggered by pharmacological effect of cyclooxygenase-1 inhibitors. Urine
      sampling is a non-invasive research tool for time-course measurements in clinical
      investigations. The urinary stable metabolite concentration of arachidonic acid
      products provides a time-integrated estimate of the production of the parent
      compounds in vivo. AIA patients exhibits significantly higher urinary
      concentrations of leukotriene E(4) (LTE(4)) and 1,15-dioxo-9alpha-hydroxy-2,3,4,5
      tetranorprostan-1,20-dioic acid (tetranor-PGDM), a newly identified metabolite of
      PGD(2), at baseline. This finding suggests the possibility that increased mast
      cell activation is involved in the pathophysiology of AIA even in a clinically
      stable condition. In addition, lower urinary concentrations of primary
      prostaglandin E(2) and 15-epimer of lipoxin A(4) at baseline in the AIA patients
      suggest that the impaired anti-inflammatory elements may also contribute to the
      severe clinical outcome of AIA. During the AIA reaction, the urinary
      concentrations of LTE(4) and PGD(2) metabolites, including tetranor-PGDM
      significantly and correlatively increase. It is considered that mast cell
      activation probably is a pathophysiologic hallmark of AIA. However, despite the
      fact that cyclooxygenease-1 is the dominant in vivo PGD(2) biosynthetic pathway,
      the precise mechanism underlying the PGD(2) overproduction resulting from the
      pharmacological effect of cyclooxygenease-1 inhibitors in AIA remains unknown. A
      comprehensive analysis of the urinary concentration of inflammatory mediators may
      afford a new research target in elucidating the pathophysiology of AIA.

PMID- 22627851
TI  - Infectious disease: Pro-resolving lipids offer a helping hand to antibiotics.

PMID- 22627853
TI  - Transplant immunology: Gut bugs and grafts.

PMID- 22627854
TI  - Mucosal immunology: Inflammasomes induce sepsis following community breakdown.

PMID- 22627855
TI  - Innate immunity: Pathogen and xenobiotic sensing - back to basics.

PMID- 22627859
TI  - Emerging concepts in haematopoietic cell transplantation.
AB  - Haematopoietic cell transplantation (HCT) is the most widely used form of
      cellular therapy. It is the only known cure for some haematological malignancies
      and has recently been used in additional clinical settings, such as allograft
      tolerance induction and treatment of autoimmune diseases. Recent advances have
      enabled HCT in a wider range of patients with improved outcomes. This Review
      summarizes the latest developments in this therapy, focusing on issues that will
      affect future advancement.

PMID- 22627860
TI  - Regulatory immune cells in transplantation.
AB  - Immune regulation is fundamental to any immune response to ensure that it is
      appropriate for the perceived threat to the host. Following cell and organ
      transplantation, it is essential to control both the innate immune response
      triggered by the injured tissue and the adaptive immune response stimulated by
      mismatched donor and recipient histocompatibility antigens to enable the
      transplant to survive and function. Here, we discuss the leukocyte populations
      that can promote immune tolerance after cell or solid-organ transplantation. Such
      populations include regulatory T cells, B cells and macrophages, as well as
      myeloid-derived suppressor cells, dendritic cells and mesenchymal stromal cells.
      We consider the potential of these regulatory immune cells to develop and
      function in transplant recipients and their potential use as cellular therapies
      to promote long-term graft function.

PMID- 22627861
TI  - The role of complement in the early immune response to transplantation.
AB  - The complement system is a key element of the innate immune system, and the
      production of complement components can be divided into central (hepatic) and
      peripheral compartments. Essential complement components such as C3 are produced
      in both of these compartments, but until recently the functional relevance of the
      peripheral synthesis of complement was unclear. Here, we review recent findings
      showing that local peripheral synthesis of complement in a transplanted organ is
      required for the immediate response of the donor organ to tissue stress and for
      priming alloreactive T cells that can mediate transplant rejection. We also
      discuss recent insights into the role of complement in antibody-mediated
      rejection, and we examine how new treatment strategies that take into account the
      separation of central and peripheral production of complement are expected to
      make a difference to transplant outcome.

PMID- 22627863
TI  - Prevalence of factor V Leiden and G20210A prothrombin mutation in the Dutch
      Famine Birth Cohort: a possible survival advantage?

PMID- 22627862
TI  - The impact of infection and tissue damage in solid-organ transplantation.
AB  - Investigations over the past two decades are revealing complexities in the
      regulation of the innate immune response, and how this response, in turn,
      controls adaptive immunity. Microbial exposure, infections and tissue damage that
      accompany solid-organ transplantation result in the release of pathogen- and
      damage-associated molecular patterns, as well as pathogen- or allograft-derived
      antigens. Here, we review these triggers of innate and adaptive immunity, and
      discuss emerging paradigms of the many ways in which infections and tissue damage
      might directly or indirectly affect alloreactivity and the outcome of
      transplanted allografts.

PMID- 22627864
TI  - High-titer n-butanol production by clostridium acetobutylicum JB200 in fed-batch
      fermentation with intermittent gas stripping.
AB  - Acetone-butanol-ethanol (ABE) fermentation with a hyper-butanol producing
      Clostridium acetobutylicum JB200 was studied for its potential to produce a high
      titer of butanol that can be readily recovered with gas stripping. In batch
      fermentation without gas stripping, a final butanol concentration of 19.1 g/L was
      produced from 86.4 g/L glucose consumed in 78 h, and butanol productivity and
      yield were 0.24 g/L h and 0.21 g/g, respectively. In contrast, when gas stripping
      was applied intermittently in fed-batch fermentation, 172 g/L ABE (113.3 g/L
      butanol, 49.2 g/L acetone, 9.7 g/L ethanol) were produced from 474.9 g/L glucose
      in six feeding cycles over 326 h. The overall productivity and yield were 0.53
      g/L h and 0.36 g/g for ABE and 0.35 g/L h and 0.24 g/g for butanol, respectively.
      The higher productivity was attributed to the reduced butanol concentration in
      the fermentation broth by gas stripping that alleviated butanol inhibition,
      whereas the increased butanol yield could be attributed to the reduced acids
      accumulation as most acids produced in acidogenesis were reassimilated by cells
      for ABE production. The intermittent gas stripping produced a highly concentrated
      condensate containing 195.9 g/L ABE or 150.5 g/L butanol that far exceeded
      butanol solubility in water. After liquid-liquid demixing or phase separation, a
      final product containing ~610 g/L butanol, ~40 g/L acetone, ~10 g/L ethanol, and
      no acids was obtained. Compared to conventional ABE fermentation, the fed-batch
      fermentation with intermittent gas stripping has the potential to reduce at least
      90% of energy consumption and water usage in n-butanol production from glucose.

PMID- 22627866
TI  - Behaviour of human physeal chondro-progenitorcells in early growth plate injury
      response in vitro.
AB  - PURPOSE: The aim of this study was to investigate the proliferation and
      differentiation behaviour of a defined cell population gained from the human
      growth plate, namely, chondro-progenitorcells (CPCs), in the initial inflammatory
      phase of growth plate injury response in vitro. METHODS: Growth plate cells were
      sorted via FACS and differentiated along adipogenic and osteogenic lineage to
      confirm their progenitor features. To mimic the inflammatory phase of injury
      response at the growth plate they were treated with IL-1beta and exposed to
      cyclic mechanical loading. A BrdU assay was used to investigate CPC
      proliferation. CPC differentiation behaviour was analysed by RT-PCR. RESULTS:
      CPCs (CD45-, CD34-, CD73+, CD90+, and CD105+) showed a successful differentiation
      along adipogenic and osteogenic lineage. Under conditions simulating the
      inflammatory phase of injury response at the growth plate in vitro CPCs
      differentiated towards hypertrophy while chondrogenesis and ossification were
      inhibited. Proliferation was not significantly altered. CONCLUSION: This study
      showed that CPCs can be isolated from the human growth plate and expanded in
      vitro. In the first phase of injury response at the growth plate these cells
      differentiate towards hypertrophy. As longitudinal growth is obtained by
      chondrocyte proliferation and volume increase during hypertrophy this maturation
      might be the first step towards post-traumatic growth disorders such as unwanted
      premature ossification of the growth plate.

PMID- 22627867
TI  - Decline in early childhood respiratory tract infections in the Norwegian mother
      and child cohort study after introduction of pneumococcal conjugate vaccination.
AB  - BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced
      into the Norwegian Childhood Immunization Program in 2006. A substantial
      effectiveness of PCV7 immunization against invasive pneumococcal disease has been
      demonstrated, whereas evidence of its impact on respiratory tract infections are
      less consistent. METHODS: This study included children participating in the
      Norwegian Mother and Child Cohort Study, which recruited pregnant women between
      1999 and 2008. Maternal report of acute otitis media (AOM), lower respiratory
      tract infections (LRTIs) and asthma in the child was compared by PCV7
      immunization status, as obtained from the Norwegian Immunization Registry.
      Generalized linear models with the log-link function were used to report adjusted
      relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: For children
      who had received 3 or more PCV7 immunizations by 12 months of age, the adjusted
      RRs of AOM and LRTIs between 12 and 18 months were 0.86 (95% CI: 0.81, 0.91) and
      0.78 (95% CI: 0.70, 0.87) respectively, when compared with nonimmunized children.
      A reduced risk of AOM, RR 0.92 (95% CI: 0.90, 0.94), and LRTIs, RR 0.75 (95% CI:
      0.71, 0.80), between 18 and 36 months of age was also identified among children
      who had received 3 or more immunizations by 18 months of age. No association was
      seen between PCV7 immunization and asthma at 36 months of age. CONCLUSION:
      Reduced incidences of AOM and LRTIs before 36 months of age were observed among
      children immunized with PCV7 through the childhood immunization program.

PMID- 22627868
TI  - Herpes zoster in a partially vaccinated pediatric population in central Israel.
AB  - BACKGROUND: This study was performed during an era of partial vaccination with
      varicella vaccine in Israel to characterize ambulatory pediatric herpes zoster
      (HZ) cases in a population with partial varicella vaccination coverage. METHODS:
      Data were collected from computerized databases of a population of 114,000
      children. Records of children aged 0-18 years, diagnosed with HZ during 2006 to
      2008 were reviewed by pediatric infectious diseases experts. Telephone interviews
      were done with a sample of the parents to get further clinical details. RESULTS:
      Of 692 medical records reviewed, 450 cases were approved for analysis, and 77
      interviews were conducted. Incidence of HZ was 130 of 100,000 person life-years.
      Peak incidence was detected in children aged 9-11 years (222/100,000 person life
      years). Pain and fever accompanied 52% and 13% of episodes, respectively. Higher
      risk for HZ was found in children who had varicella during their first year of
      life (relative risk and 95% confidence interval: 13.5[9.6-18.8]; P < 0.001), and
      in children who had varicella during the second year of life (relative risk = 2
      [1.5-2.6]; P < 0.001). Vaccination was found to be protective against HZ
      (relative risk = 0.42 [0.33-0.55]; P < 0.001). CONCLUSIONS: The epidemiology of
      HZ seems to be changing in a population with partial varicella vaccination rate.
      Our results may suggest that children who contracted chicken pox in their first
      year of life may benefit from varicella vaccination.

PMID- 22627869
TI  - Pharmacokinetics and tolerability of single-dose daptomycin in young infants.
AB  - BACKGROUND: Daptomycin is approved for the treatment of complicated skin and skin
      structure infections and Staphylococcus aureus bacteremia. We sought to
      characterize daptomycin single-dose pharmacokinetics and tolerability in young
      infants. METHODS: Subjects < 120 days of age with suspected systemic infections
      were eligible for inclusion. Each subject was given a single 6 mg/kg intravenous
      dose of daptomycin. An average of 4 postdose concentrations per infant was
      obtained. RESULTS: Data from 20 infants are presented. Median gestational age at
      birth and postnatal age were 32 weeks (range: 23, 40) and 3 days (1, 85),
      respectively. The median area under the concentration curve at 24 hours, volume
      of distribution, total body clearance and half-life of daptomycin were 262.4
      mg*h/L (166.7, 340.2), 0.21 L/kg (0.11, 0.34), 0.021 L/h/kg (0.016, 0.034) and
      6.2 hours (3.7, 9.0), respectively. No adverse events related to daptomycin were
      observed, including changes in creatine phosphokinase concentrations.
      CONCLUSIONS: Daptomycin clearance in young infants was similar to that in
      children 2-6 years of age and higher than that observed in adolescents and
      adults.

PMID- 22627870
TI  - Pharmacokinetics and safety of fluconazole in young infants supported with
      extracorporeal membrane oxygenation.
AB  - BACKGROUND: Candida infections are a leading cause of infectious disease-related
      death in infants supported with extracorporeal membrane oxygenation (ECMO). The
      ECMO circuit can alter drug pharmacokinetics; thus, standard fluconazole dosing
      in children on ECMO may result in suboptimal drug exposure. This study determined
      the pharmacokinetics of fluconazole in infants on ECMO. METHODS: Infants <120
      days of age received either intravenous fluconazole prophylaxis (25 mg/kg once a
      week) or treatment (12 mg/kg daily) while on ECMO. Paired plasma samples were
      collected preoxygenator and postoxygenator around doses 1 and 2 to calculate
      pharmacokinetic indices and describe oxygenator extraction. A 1-compartment model
      was fit to the data using nonlinear regression. Surrogate pharmacodynamic targets
      for efficacy were evaluated. RESULTS: Ten infants were enrolled. After dose 1 (n
      = 9), the median clearance was 17 mL/kg/h, the median volume of distribution was
      1.5 L/kg and the median exposure in the first 24 hours (area under the curve from
      0 to 24 hours) was 322 h * mg/L. After multiple doses (n = 7), the median
      clearance was 22 mL/kg/h, the median volume of distribution was 1.9 L/kg and the
      area under the curve from 0 to 24 hours was 352 h * mg/L. After dose 1, 78% of
      infants achieved the prophylaxis target, whereas only 11% achieved the
      therapeutic target. Oxygenator extraction of fluconazole was minimal (-2.0%,
      standard deviation 15.0), and extraction was not correlated with age of the ECMO
      circuit (rho= -0.05). There were no adverse events related to fluconazole.
      CONCLUSIONS: Infants on ECMO had higher volume of distribution but similar
      clearance when compared with historical controls not on ECMO. In infants on ECMO,
      a fluconazole dose of 25 mg/kg weekly provides adequate exposure for prophylaxis
      against Candida infections. However, higher doses may be needed for treatment.

PMID- 22627871
TI  - Interactions of physical, chemical, and biological weather calling for an
      integrated approach to assessment, forecasting, and communication of air quality.
AB  - This article reviews interactions and health impacts of physical, chemical, and
      biological weather. Interactions and synergistic effects between the three types
      of weather call for integrated assessment, forecasting, and communication of air
      quality. Today's air quality legislation falls short of addressing air quality
      degradation by biological weather, despite increasing evidence for the
      feasibility of both mitigation and adaptation policy options. In comparison with
      the existing capabilities for physical and chemical weather, the monitoring of
      biological weather is lacking stable operational agreements and resources.
      Furthermore, integrated effects of physical, chemical, and biological weather
      suggest a critical review of air quality management practices. Additional
      research is required to improve the coupled modeling of physical, chemical, and
      biological weather as well as the assessment and communication of integrated air
      quality. Findings from several recent COST Actions underline the importance of an
      increased dialog between scientists from the fields of meteorology, air quality,
      aerobiology, health, and policy makers.

PMID- 22627872
TI  - Phosphorus flows to and from Swedish agriculture and food chain.
AB  - Phosphorus flows in Swedish agriculture and food chain were studied by material
      flow analysis. The system studied included agriculture, food consumption, related
      waste and wastewater from private households and municipal wastewater treatment
      plants. Swedish farmland had net annual phosphorus inputs of ~12, 600 metric tons
      (4.1 kg P ha(-1)) in 2008-2010. The total import of phosphorus in food and feed
      to Sweden exceed imports of phosphorus in fertilizers. Despite strict animal
      density regulations relating to manure phosphorus content, phosphorus is
      accumulating on Swedish animal farms. The total quantity of manure produced
      greatly exceeds imported mineral phosphorus fertilizer and almost equals total
      phosphorus inputs to Swedish farmland.

PMID- 22627873
TI  - Land banking: a mechanism for urban sustainable development in China.

PMID- 22627879
TI  - Encapsulation of proteins into tunable and giant mesocage alumina.
AB  - Protein bioadsorption has rapidly attracted attention partially because of the
      promising advances in diagnostic assays, sensors, separations, and gene
      technology. Tunable and giant mesocage alumina cavities (5 nm to 20 nm) show
      capability in size-selective encapsulation and diffusivity of large proteins into
      interior pores.

PMID- 22627880
TI  - Purification of recombinant protein by cold-coacervation of fusion constructs
      incorporating resilin-inspired polypeptides.
AB  - Polypeptides containing between 4 and 32 repeats of a resilin-inspired sequence
      AQTPSSYGAP, derived from the mosquito Anopheles gambiae, have been used as tags
      on recombinant fusion proteins. These repeating polypeptides were inspired by the
      repeating structures that are found in resilins and sequence-related proteins
      from various insects. Unexpectedly, an aqueous solution of a recombinant resilin
      protein displays an upper critical solution temperature (cold-coacervation) when
      held on ice, leading to a separation into a protein rich phase, typically
      exceeding 200 mg/mL, and a protein-poor phase. We show that purification of
      recombinant proteins by cold-coacervation can be performed when engineered as a
      fusion partner to a resilin-inspired repeat sequence. In this study, we
      demonstrate the process by the recombinant expression and purification of
      enhanced Green fluorescent protein (EGFP) in E. coli. This facile purification
      system can produce high purity, concentrated protein solutions without the need
      for affinity chromatography or other time-consuming or expensive purification
      steps, and that it can be used with other bulk purification steps such as low
      concentration ammonium sulfate precipitation. Protein purification by cold
      coacervation also minimizes the exposure of the target protein to enhanced
      proteolysis at higher temperature.

PMID- 22627881
TI  - Replication of RYR3 gene polymorphism association with cIMT among HIV-infected
      whites.
AB  - To replicate the association of variants in RYR3 gene with common carotid intima
      media thickness (cIMT), a surrogate marker of atherosclerosis, we genotyped
      single nucleotide polymorphisms (SNPs) rs2229116 and rs7177922 in a sub
      population of 244 HIV-positive and HIV-negative men. SNP rs2229116 was associated
      with common cIMT in HIV infected white men after adjusting for age and use of
      stavudine (d4T). The association was more evident at younger ages and decreased
      among older individuals.

PMID- 22627882
TI  - A fluorolaser navigation system to guide linear surgical tool insertion.
AB  - PURPOSE: Conventional navigation systems for minimally invasive orthopedic
      surgery require a secondary monitor to display guidance information generated
      with CT or MRI images. Newer systems use augmented reality to project surgical
      plans into binocular glasses. These surgical procedures are often mentally
      challenging and cumbersome to perform. METHOD: A comprehensive surgical
      navigation system for direct guidance while minimizing radiation exposure was
      designed and built. System accuracy was evaluated using in vitro needle insertion
      experiments. The fluoroscopic-based navigation technique is combined with an
      existing laser guidance technique. As a result, the combined system is capable of
      surgical planning using two or more X-ray images rather than CT or MRI scans.
      Guidance information is directly projected onto the patient using two laser beams
      and not via a secondary monitor. RESULTS: We performed 15 in vitro needle
      insertion experiments as well as 6 phantom pedicle screw insertion experiments to
      validate navigation system accuracy. The planning accuracy of the system was
      found to be 2.32 mm and 2.28 degrees , while its overall guidance accuracy was
      found to be 2.40 mm and 2.39 degrees . System feasibility was demonstrated by
      successfully performing percutaneous pin insertion on phantoms. CONCLUSION:
      Quantitative and qualitative evaluations of the fluorolaser navigation system
      show that it can support accurate guidance and intuitive surgical tool insertion
      procedures without preoperative 3D image volumes and registration processes.

PMID- 22627883
TI  - Effect of non-specific reversal agents on anticoagulant activity of dabigatran
      and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers.
AB  - The new anticoagulants dabigatran and rivaroxaban can be responsible for
      haemorrhagic complications. As for any anticoagulant, bleeding management is
      challenging. We aimed to test the effect of all putative haemostatic agents on
      the anticoagulant activity of these new drugs using thrombin generation tests. In
      an  ex vivo  study, 10 healthy white male subjects were randomised to receive
      rivaroxaban (20 mg) or dabigatran (150 mg) in one oral administration. After a
      two weeks washout period, they received the other anticoagulant. Venous blood
      samples were collected just before drug administration (H0) and 2 hours
      thereafter. Reversal of anticoagulation was tested  in vitro  using prothrombin
      complex concentrate (PCC), rFVIIa or FEIBA(r) at various concentrations.
      Rivaroxaban affects quantitative and kinetic parameters, including the endogenous
      thrombin potential (ETP-AUC and more pronouncedly the thrombin peak), the lag
      time and time to peak. PCC strongly corrected ETP-AUC, whereas rFVIIa only
      modified the kinetic parameters. FEIBA corrected all parameters. Dabigatran
      specially affects the kinetics of thrombin generation with prolonged lag-time and
      time to peak. Although PCC increased ETP-AUC, only rFVIIa and FEIBA corrected the
      altered lag-time. For both anticoagulants, lower doses of FEIBA, corresponding to
      a quarter to half the dose usually used, have potential reversal profile of
      interest. In conclusion, some non-specific reversal agents appear to be able to
      reverse the anticoagulant activity of rivaroxaban or dabigatran. However,
      clinical evaluation is needed regarding haemorrhagic situations, and a meticulous
      risk-benefit evaluation regarding their use in this context is required.

PMID- 22627884
TI  - Acute exercise adjustments of cardiovascular autonomic control in diabetic rats.
AB  - INTRODUCTION: We evaluated the role of cardiovascular autonomic changes in
      hemodynamics at rest and in response to exercise in streptozotocin-induced
      diabetic rats. METHODS: Male Wistar rats were divided into nondiabetic (ND, n =
      8) and diabetic (D, n = 8) groups. Arterial pressure signals were recorded in the
      basal state and after atropine or propranolol injections at rest, during exercise
      and during recovery. RESULTS: At rest, vagal tonus was reduced in D (37 +/- 3
      bpm) in comparison with the ND group (61 +/- 9 bpm). Heart rate during exercise
      was lower in D in relation to ND rats associated with reduced vagal withdrawal in
      the D group. The D rats had an increase in vagal tonus in the recovery period (49
      +/- 6 bpm). CONCLUSIONS: Exercise-induced hemodynamic adjustment impairment in
      diabetic rats was associated with reduced cardiac vagal control. The vagal
      dysfunction was attenuated after aerobic exercise, reinforcing the positive role
      of this approach in the management of cardiovascular risk in diabetics.

PMID- 22627887
TI  - Bacillus cereus endocarditis in native aortic valve.
AB  - Bacillus cereus endocarditis is rare. It has been implicated in immunocompromised
      individuals, especially in intravenous drug users as well as in those with a
      cardiac prosthesis. The patient was a 31-year-old ex-intravenous drug addict with
      a past history of staphylococcal pulmonary valve endocarditis, who presented with
      symptoms of decompensated cardiac failure. Echocardiography showed severe aortic
      regurgitation with an oscillating vegetation seen on the right coronary cusp of
      the aortic valve. The blood cultures grew Bacillus cereus. We report this as a
      rare case of Bacillus cereus endocarditis affecting a native aortic valve.

PMID- 22627889
TI  - Diagnostic and prognostic performance of a novel high-sensitivity cardiac
      troponin T assay compared to a contemporary sensitive cardiac troponin I assay in
      patients with acute coronary syndrome.
AB  - OBJECTIVE: The study sought to compare the clinical performance of two more
      sensitive cardiac troponin (cTn) assays, a novel high-sensitivity (hs) troponin T
      assay and a contemporary cTnI assay. METHODS: We measured hs-cTnT (Roche TnThs)
      and cTnI (Siemens Centaur Ultra) on presentation in 1,384 patients with suspected
      acute coronary syndrome (ACS) who underwent early invasive strategy within 24 h
      after presentation. Kaplan-Meier, Cox proportional hazards, and receiver
      operating characteristic (ROC) analysis was used to compare their prognostic
      performance for the prediction of all-cause death and death/MI (myocardial
      infarction) after a median of 271 days. We also compared the diagnostic
      performance of these assays on presentation for early diagnosis of non-STEMI.
      RESULTS: Both hs-cTnT and cTnI were independently predictive of long-term death
      (OR 3.51 vs. 2.19) and the composite of death/MI (OR 9.24 vs. 3.61), across the
      spectrum of ACS and in patients without ACS. When used as a continuous variable,
      ROC analysis demonstrated significantly higher areas under the curve (AUC) for hs
      cTnT as compared to cTnI for the prediction of death/MI (0.721 vs. 0.672, P =
      0.024), a trend to better prediction of all-cause death (0.721 vs. 0.672, P =
      0.093) and significantly higher AUC for early diagnosis of non-STEMI (0.965 vs.
      0.901, P < 0.001). CONCLUSION: Using the 99th percentile cutoff for hs-cTnT and
      cTnI, both assays enable prediction of adverse long-term outcomes and earlier
      diagnosis of non-STEMI. Used as a continuous variable, the hs-cTnT assay showed
      superior performance compared to the cTnI assay, especially in regard to
      prognosis.

PMID- 22627890
TI  - Assessment of an asymmetrical coating stent with sirolimus released from ablumial
      matrix in porcine model.
AB  - BACKGROUND: Delayed endothelialization contributes to stent thrombosis of current
      drug-eluting stents. The asymmetrical coating technique provides an anti
      proliferative effect abluminally without affecting luminal endothelialization.
      Layer-by-layer self-assembled chitosan/heparin (C/H LBL) has been proved to
      promote re-endothelialization. A novel stent system, C/H LBL coated luminally and
      sirolimus released abluminally (C/H LBL-SES), was fabricated. METHODS: Bare metal
      stents (BMS), traditionally circumferential sirolimus-eluting stents (SES), and
      C/H LBL-SES were implanted into porcine coronary arteries. At the 7, 14 and 28
      days follow-up (FU), angiography, intravascular ultrasound (IVUS), vasomotor
      function induced by acetylcholine (Ach), scanning-electron microscopy and
      histopathology were performed. Remodeling index (RI) was based on IVUS and
      defined as cross-sectional area (CSA) of vessel at in-stent segment divided by
      CSA of reference vessel and expressed as a percentage with a normal range from
      0.95 to 1.05. RESULTS: Thirty-eight mini pigs were enrolled and 74 stents (BMS =
      23, C/H LBL = 28, SES = 23) were implanted in this study. At 28 days after
      implantation, the diameter stenosis of C/H LBL-SES by quantitative coronary
      angiography was 18.8 +/- 2.5 %, the area stenosis by histomorphometry was 24.2 +/
      2.9 %, which were comparable to that of SES and superior to BMS. At 14 days, re
      endothelialization of C/H LBL-SES was almost completed, while only about 50 % of
      surface of SES was covered by endothelium. At 7, 14 and 28 days FU, although C/H
      LBL-SES suffered a greater vasoconstriction induced by Ach infusion than BMS (P <
      0.05), it behaved better than SES (P < 0.01). No sign of stent malapposition was
      detected, while RI was within the normal range by IVUS. No acute or subacute
      thrombotic events occurred in all three groups. CONCLUSIONS: The asymmetrically
      designed C/H LBL-SES successfully inhibited neointima hyperplasia, while
      diminishing vasoconstriction after Ach-stress. Endothelialization of C/H LBL-SES
      was less affected compared with traditionally circumferentially coated SES.

PMID- 22627892
TI  - Renal transplantation: Making kidneys count.

PMID- 22627891
TI  - Visualizing feasible operating ranges within tissue engineering systems using a
      "windows of operation" approach: a perfusion-scaffold bioreactor case study.
AB  - Tissue engineering approaches to developing functional substitutes are often
      highly complex, multivariate systems where many aspects of the biomaterials, bio
      regulatory factors or cell sources may be controlled in an effort to enhance
      tissue formation. Furthermore, success is based on multiple performance criteria
      reflecting both the quantity and quality of the tissue produced. Managing the
      trade-offs between different performance criteria is a challenge. A "windows of
      operation" tool that graphically represents feasible operating spaces to achieve
      user-defined levels of performance has previously been described by researchers
      in the bio-processing industry. This paper demonstrates the value of "windows of
      operation" to the tissue engineering field using a perfusion-scaffold bioreactor
      system as a case study. In our laboratory, perfusion bioreactor systems are
      utilized in the context of bone tissue engineering to enhance the osteogenic
      differentiation of cell-seeded scaffolds. A key challenge of such perfusion
      bioreactor systems is to maximize the induction of osteogenesis but minimize cell
      detachment from the scaffold. Two key operating variables that influence these
      performance criteria are the mean scaffold pore size and flow-rate. Using
      cyclooxygenase-2 and osteopontin gene expression levels as surrogate indicators
      of osteogenesis, we employed the "windows of operation" methodology to rapidly
      identify feasible operating ranges for the mean scaffold pore size and flow-rate
      that achieved user-defined levels of performance for cell detachment and
      differentiation. Incorporation of such tools into the tissue engineer's armory
      will hopefully yield a greater understanding of the highly complex systems used
      and help aid decision making in future translation of products from the bench top
      to the market place.

PMID- 22627893
TI  - A heme degradation enzyme, HutZ, from Vibrio cholerae.
AB  - HutZ, one of the crucial proteins of the iron uptake system in Vibrio cholerae,
      was purified, which binds to heme at a stoichiometry of 1 : 1. In the presence of
      ascorbic acid, the HutZ-bound heme degrades via the same intermediates observed
      in heme oxygenase, suggesting that HutZ works as a heme degradation enzyme.

PMID- 22627894
TI  - The SOA formation model combined with semiempirical quantum chemistry for
      predicting UV-Vis absorption of secondary organic aerosols.
AB  - A new model for predicting the UV-visible absorption spectra of secondary organic
      aerosols (SOA) has been developed. The model consists of two primary parts: a SOA
      formation model and a semiempirical quantum chemistry method. The mass of SOA is
      predicted using the PHRCSOA (Partitioning Heterogeneous Reaction Consortium
      Secondary Organic Aerosol) model developed by Cao and Jang [Environ. Sci.
      Technol., 2010, 44, 727]. The chemical composition is estimated using a
      combination of the kinetic model (MCM) and the PHRCSOA model. The absorption
      spectrum is obtained by taking the sum of the spectrum of each SOA product
      calculated using a semiempirical NDDO (Neglect of Diatomic Differential Overlap)
      based method. SOA was generated from the photochemical reaction of toluene or
      alpha-pinene at different NO(x) levels (low NO(x): 24-26 ppm, middle NO(x): 49
      ppb, high NO(x): 104-105 ppb) using a 2 m(3) indoor Teflon film chamber. The
      model simulation reasonably agrees with the measured absorption spectra of alpha
      pinene SOA but underestimates toluene SOA under high and middle NO(x) conditions.
      The absorption spectrum of toluene SOA is moderately enhanced with increasing
      NO(x) concentrations, while that of alpha-pinene SOA is not affected. Both
      measured and calculated UV-visible spectra show that the light absorption of
      toluene SOA is much stronger than that of alpha-pinene SOA.

PMID- 22627902
TI  - A new general biomarker-based incidence estimator.
AB  - BACKGROUND: Estimating disease incidence from cross-sectional surveys, using
      biomarkers for "recent" infection, has attracted much interest. Despite
      widespread applications to HIV, there is currently no consensus on the correct
      handling of biomarker results classifying persons as "recently" infected long
      after the infections occurred. METHODS: We derive a general expression for a
      weighted average of recent incidence that-unlike previous estimators-requires no
      particular assumption about recent infection biomarker dynamics or about the
      demographic and epidemiologic context. This is possible through the introduction
      of an explicit timescale T that truncates the period of averaging implied by the
      estimator. RESULTS: The recent infection test dynamics can be summarized into 2
      parameters, similar to those appearing in previous estimators: a mean duration of
      recent infection and a false-recent rate. We identify a number of dimensionless
      parameters that capture the bias that arises from working with tractable forms of
      the resulting estimator and elucidate the utility of the incidence estimator in
      terms of the performance of the recency test and the population state. Estimation
      of test characteristics and incidence is demonstrated using simulated data. The
      observed confidence interval coverage of the test characteristics and incidence
      is within 1% of intended coverage. CONCLUSIONS: Biomarker-based incidence
      estimation can be consistently adapted to a general context without the strong
      assumptions of previous work about biomarker dynamics and epidemiologic and
      demographic history.

PMID- 22627901
TI  - Depression and serotonin reuptake inhibitor treatment as risk factors for preterm
      birth.
AB  - BACKGROUND: Major depressive disorder and the use of serotonin reuptake
      inhibitors (SRIs) in pregnancy have been associated with preterm birth. Studies
      that have attempted to separate effects of illness from treatment have been
      inconclusive. We sought to explore the separate effects of SRI use and major
      depressive episodes in pregnancy on risk of preterm birth. METHODS: We conducted
      a prospective cohort study of 2793 pregnant women, oversampled for a recent
      episode of major depression or use of an SRI. We extracted data on birth outcomes
      from hospital charts and used binary logistic regression to model preterm birth
      (<37 weeks' gestation). We used ordered logistic regression to model early (<34
      weeks' gestation) or late (34-36 weeks) preterm birth, and we used nominal
      logistic regression to model preterm birth antecedents (spontaneous preterm
      labor/preterm premature rupture of membranes/preterm for medical
      indications/term). RESULTS: Use of an SRI, both with (odds ratio = 2.1 [95%
      confidence interval = 1.0-4.6]) and without (1.6 [1.0-2.5]) a major depressive
      episode, was associated with preterm birth. A major depressive episode without
      SRI use (1.2 [0.68-2.1]) had no clear effect on preterm birth risk. None of these
      exposures was associated with early preterm birth. Use of SRIs in pregnancy was
      associated with increases in spontaneous but not medically indicated preterm
      birth. CONCLUSIONS: SRI use increased risk of preterm birth. Although the effect
      of a major depressive episode alone was unclear, symptomatic women undergoing
      antidepressant treatment had elevated risk.

PMID- 22627903
TI  - The wild side of life: Drosophila reproduction in nature.
AB  - Drosophila species vary in the rates at which females remate and the number of
      sperm they receive in the laboratory. In species such as D. melanogaster and D.
      pseudoobscura, in which females receive thousands of sperm and remate
      infrequently compared with species such as D. hydei and D. nigrospiracula, where
      females receive only a few hundred sperm and remate many times in a day, wild
      caught females should produce far more progeny. We tested this prediction by
      collecting, directly from nature, females of six species whose remating rates and
      number of sperm received vary from high to low and assessing the proportion of
      females with sperm and the number of progeny females produce. Over 95% of D.
      pseudoobscura and D. melanogaster females were inseminated while far fewer of the
      other species contained any sperm. In addition, D, pseudoobscura females produced
      progeny for over two weeks, D. melanogaster for over a week, while D. hydei and
      D. nigrospiracula females ran out of sperm after 1-2 d. These observations
      suggest extreme sperm limitation in these latter species.

PMID- 22627904
TI  - Anticoagulation in ambulatory cancer patients with no indication for prophylactic
      or therapeutic anticoagulation: a cost-effectiveness analysis from a U.S.
      perspective.
AB  - Venous thromboembolism (VTE) occurs frequently in cancer patients and is a major
      cause of mortality. Although anticoagulation (AC) may have anti-tumour effects,
      it is recommended in cancer patients only for indications unrelated to these
      effects. A Markov model was constructed to estimate when prophylactic AC, given
      during four months of chemotherapy following a new cancer diagnosis, would be
      economically reasonable in ambulatory cancer patients with no VTE history. Risks
      and costs of major and minor bleeding, VTE, and death were obtained from the
      literature, including a 2011 Cochrane review of AC in cancer inpatients with no
      conventional indication. In the model, AC was low-molecular-weight-heparin
      (LMWH), and effects were modeled over a 24-month period. Model outputs were
      quality-adjusted life years (QALY) and the incremental cost-effectiveness ratio
      (ICER). In the base case analysis, when prophylactic AC had a two-year relative
      mortality risk of 0.92, there was a gain of 0.0354 QALY, for an ICER of
      $90,893/QALY gained, compared with no AC. In sensitivity analyses, AC prophylaxis
      cost less than $100,000/QALY, if two-year mortality exceeded 75%, or if AC costs
      were less than $1,076 per month, or if LMWH relative mortality risk was less than
      0.927. Results were not sensitive to variation in VTE relative risk on AC, nor to
      major or minor bleeding risk on AC. A probabilistic sensitivity analysis also
      favoured prophylactic AC. In conclusion, prophylactic LMWH given to decrease
      cancer-related mortality, with no conventional indication, appears economically
      reasonable if its suggested mortality benefit is confirmed in future trials.

PMID- 22627907
TI  - Liver foreign body resembling carcinoma.

PMID- 22627908
TI  - Why meta-analyses on the same topic lead to different conclusions?

PMID- 22627909
TI  - Further experience with the local lymph node assay using standard radioactive and
      nonradioactive cell count measurements.
AB  - In a previous study, the predictive capacity of a modified local lymph node assay
      (LLNA) based on cell counts, the LNCC, was demonstrated to be closely similar to
      that of the original assay. In addition, a range of substances, including some
      technical/commercial materials and a range of agrochemical formulations (n = 180)
      have also been assessed in both methods in parallel. The results in the LNCC and
      LLNA were generally consistent, with 86% yielding an identical classification
      outcome. Discordant results were associated with borderline data and were evenly
      distributed between the two methods. Potency information derived from each method
      also demonstrated good consistency (n = 101), with 93% of predictions being
      close. Skin irritation was observed only infrequently and was most commonly
      associated with positive results; it was not associated with the discordant
      results. Where different vehicles were used with the same test material, the
      effect on sensitizing activity was modest, consistent with historical data.
      Analysis of positive control data indicated that the LNCC and LLNA displayed
      similar levels of biological variation. When taken in combination with the
      previously published results on LLNA Performance Standard chemicals, it is
      concluded that the LNCC provides a viable non-radioactive alternative to the LLNA
      for the assessment of substances, including potency predictions, as well as for
      the evaluation of preparations.

PMID- 22627910
TI  - Assessment of protein entrapment in hydroxyapatite scaffolds by size exclusion
      chromatography.
AB  - Although it is well known that the textural properties of scaffolds play an
      important role in the process of tissue regeneration, the investigation of such
      effects remain difficult especially at the micro/nano level. Texture confers the
      material the additional ability to entrap/concentrate molecules circulating in
      the body fluid regardless of their binding affinity to the material. The goal of
      the present work is to isolate protein entrapment from protein adsorption
      phenomena in two macroporous hydroxyapatite scaffolds with identical chemical
      structure, similar macroporosity but different micro/nanoporosity using proteins
      of different sizes. This was achieved implementing size exclusion chromatography
      and using the scaffolds as chromatographic columns. The results showed that the
      larger the crystal size and the lower the packing density of the crystals
      composing the scaffold increased protein retention but decreased the protein
      dwelling time in the column. Differences in the amount of protein retained
      depended on the protein type.

PMID- 22627911
TI  - Cloning of a trypsin-like serine protease and expression patterns during
      Plasmodium falciparum invasion in the mosquito, Anopheles dirus (Peyton and
      Harrison).
AB  - Understanding specific gene regulation during responses to malaria infection is
      key to dissecting the mosquito defense mechanisms and host/parasite interactions.
      A full-length serine protease cDNA was isolated from the fat body of female
      Anopheles dirus, a major malaria vector in Thailand. The predicted amino acid
      sequence of SERF4 identifies it as a member of the serine protease family
      containing a single trypsin-like protease domain. Digestive trypsins function in
      the female mosquito midgut and are inducible in two phases in this tissue upon
      blood intake. However, the gene was highly upregulated in the midgut at day 3
      postinfection by Plasmodium falciparum. In situ hybridization confirmed that
      SERF4 transcripts were located in the midgut epithelial cells rather than
      hemocytes or other tissues associated with the midgut. SERF4 was also strongly
      downregulated in the whole insects at day 16 after infection in comparison with
      the blood-fed control. Changes in the expression of the SERF4 gene in response to
      infection with this human malaria parasite suggest a role in parasite-specific
      innate immunity.

PMID- 22627912
TI  - Effect of diet composition and weight loss on resting energy expenditure in the
      POUNDS LOST study.
AB  - Weight loss reduces energy expenditure, but it is unclear whether dietary
      macronutrient composition affects this reduction. We hypothesized that energy
      expenditure might be modulated by macronutrient composition of the diet. The
      Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST study, a
      prospective, randomized controlled trial in 811 overweight/obese people who were
      randomized in a 2 * 2 design to diets containing 20en% or 40en% fat and 15en% or
      25en% protein (diets with 65%, 55%, 45%, and 35% carbohydrate) provided the data
      to test this hypothesis. Resting energy expenditure (REE) was measured at
      baseline, 6, and 24 months using a ventilated hood. REE declined at 6 months by
      99.5 +/- 8.0 kcal/day in men and 55.2 +/- 10.6 kcal/day in women during the first
      6 months. This decline was related to the weight loss, and there was no
      difference between the diets. REE had returned to baseline by 24 months, but body
      weight was still 60% below baseline. Measured REE at 6 months was significantly
      lower than the predicted (-18.2 +/- 6.7 kcal/day) and was the result of
      significant reductions from baseline in the low-fat diets (65% or 55%
      carbohydrate), but not in the high fat diet groups. By 24 months the difference
      had reversed with measured REE being slightly but significantly higher than
      predicted (21.8 +/- 10.1 kcal/day). In conclusion, we found that REE fell
      significantly after weight loss but was not related to diet composition. Adaptive
      thermogenesis was evident at 6 months, but not at 24 months.

PMID- 22627914
TI  - Healthcare utilization and costs in severely obese subjects before bariatric
      surgery.
AB  - This study examined healthcare utilization and associated costs for a severely
      obese population before receiving bariatric surgery relative to an age- and sex
      matched sample from the Australian general population. Severely obese subjects
      receiving laparoscopic adjustable gastric banding (LAGB) surgery in 2009 (n =
      11,769) were identified. Utilization of medical services and pharmaceuticals in
      the 3.5 years before surgery were ascertained for each severely obese subject
      through linkage with Medicare, Australia's universal health insurance scheme.
      Equivalent data were retrieved for each subject from the matched general
      population sample (n = 140,000). Severely obese subjects utilized significantly
      more medical services annually compared to the general population (mean: 22.8 vs.
      12.1/person, standardized incidence ratio (SIR): 1.89 (95% confidence interval
      (CI) 1.88-1.89)), translating to twofold higher mean annual costs (Australian
      $1,140 vs. $567/person). The greatest excess costs in the obese related to
      consultations with general practitioners, psychiatrists/psychologists and other
      specialists, investigations for obstructive sleep apnea, and in vitro
      fertilization. Severely obese subjects also utilized significantly more
      pharmaceutical prescriptions annually (mean: 11.4 vs. 5.3/person, SIR 2.18 (95%
      CI: 2.17-2.19)), translating to 2.2-fold higher mean annual costs ($595/person
      vs. $270/person). The greatest excess costs in the obese related to diabetes
      drugs, lipid-modifying agents, psychoanaleptics, acid-related disorder drugs,
      agents acting on the rennin-angiotensin system, immunosuppressants, and
      obstructive airway disease drugs. Overall, healthcare costs in the severely obese
      population were more than double those incurred by the general population.

PMID- 22627913
TI  - A modified protocol to maximize differentiation of human preadipocytes and
      improve metabolic phenotypes.
AB  - Adipose stromal cells proliferate and differentiate into adipocytes, providing a
      valuable model system for studies of adipocyte biology. We compared
      differentiation protocols for human preadipocytes and report on their metabolic
      phenotypes. By simply prolonging the adipogenic induction period from the first 3
      to 7 days, the proportion of cells acquiring adipocyte morphology increased from
      30-70% to over 80% in human subcutaneous preadipocytes (passages 5-6). These
      morphological changes were accompanied by increases in the adipogenic marker
      expression and improved adipocyte metabolic phenotypes: enhanced responses to
      beta-adrenergically stimulated lipolysis and to insulin-stimulated glucose
      metabolism into triglyceride (TG). Confirming previous studies, fetal bovine
      serum (FBS) dose-dependently inhibited adipogenesis. However, in subcutaneous
      preadipocytes that differentiate well (donor-dependant high capacity and
      subcultured fewer than two times), the use of 7d-induction protocols in both 3%
      FBS and serum-free conditions allowed >80% differentiation. Responsiveness to
      beta-adrenergically stimulated lipolysis was lower in 3% FBS. Rates of insulin
      stimulated glucose uptake were higher in adipocytes differentiated with 3% FBS,
      whereas the sensitivity to insulin was almost identical between the two groups.
      In summary, extending the length of the induction period in adipogenic cocktail
      improves the degree of differentiation and responses to key metabolic hormones.
      This protocol permits functional analysis of metabolic phenotypes in valuable
      primary human adipocyte cultures through multiple passages.

PMID- 22627915
TI  - Obesity negatively impacts aerobic capacity improvements both acutely and 1-year
      following cardiac rehabilitation.
AB  - Cardiac rehabilitation (CR) produces a host of health benefits related to
      modifiable cardiovascular risk factors. The purpose of the present investigation
      was to determine the influence of body weight, assessed through BMI, on acute and
      long-term improvements in aerobic capacity following completion of CR. Three
      thousand nine hundred and ninety seven subjects with coronary artery disease
      (CAD) participated in a 12-week multidisciplinary CR program. Subjects underwent
      an exercise test to determine peak estimated metabolic equivalents (eMETs) and
      BMI assessment at baseline, immediately following CR completion and at 1-year
      follow-up. Normal weight subjects at 1-year follow-up demonstrated the greatest
      improvement in aerobic fitness and best retention of those gains (gain in peak
      METs: 0.95 +/- 1.1, P < 0.001). Although the improvement was significant (P <
      0.001), subjects who were initially classified as obese had the lowest aerobic
      capacity and poorest retention in CR fitness gains at 1-year follow-up (gain in
      peak eMETs: 0.69 +/- 1.2). Subjects initially classified as overweight by BMI had
      a peak eMET improvement that was also significantly better (P < 0.05) than obese
      subjects at 1-year follow-up (gain in peak eMETs: 0.82 +/- 1.1). Significant
      fitness gains, one of the primary beneficial outcomes of CR, can be obtained by
      all subjects irrespective of BMI classification. However, obese patients have
      poorer baseline fitness and are more likely to "give back" fitness gains in the
      long term. Obese CAD patients may therefore benefit from additional interventions
      to enhance the positive adaptations facilitated by CR.

PMID- 22627919
TI  - Regional differences in subcutaneous adipose tissue gene expression.
AB  - Adipose tissue (AT) located in the viscera is considered to be functionally and
      metabolically different from that found in the subcutaneous depot. However,
      subcutaneous AT (SAT) in generalized regions is considered to be homogeneous in
      nature. Affymetrix GeneChip Human Exon 1.0 ST Arrays were used to determine
      differential gene expression in four subcutaneous adipose depots (upper abdomen,
      lower abdomen, flank and hip) in normal weight women. A total of 2,890/24,409
      transcripts were differentially expressed between all sites. When comparing the
      hip and flank to the lower abdomen, 248 and 83 genes were differentially
      expressed, respectively. When comparing the hip and flank to the upper abdomen,
      2,480 and 79 genes were differentially expressed, respectively. No genes were
      significantly different when the lower abdomen was compared to the upper abdomen
      and the hip to the flank. Genes involved in the complement and coagulation
      cascades and immune responses showed increased expression in the lower abdomen
      compared to the flank. In addition, two genes involved in the complement and
      coagulation cascade, CR1 and C7, were expressed more highly in the lower abdomen
      compared to the hip. Genes involved in basic biochemical metabolism including
      insulin signaling, the urea cycle, glutamate metabolism, arginine and proline
      metabolism and aminosugar metabolism had higher expression in the lower abdomen
      compared to the hip. These results in normal weight healthy women provide a new
      perspective on regional differences in SAT biology that may have pathophysiologic
      implications when adiposity increases.

PMID- 22627920
TI  - Nutritional state affects the expression of the obesity-associated genes Etv5,
      Faim2, Fto, and Negr1.
AB  - Obesity is a risk factor for type II diabetes, atherosclerosis, and some forms of
      cancer. Variation in common measures of obesity (e.g., BMI, waist/hip ratio) is
      largely explained by heritability. The advent of genome-wide association studies
      (GWAS) has made it possible to identify several genetic variants that associate
      with measures of obesity, but how exactly these genetic variants contribute to
      overweight has remained largely unresolved. One first hint is given by the fact
      that many of the associated variants reside in or near genes that act in the
      central nervous system, which implicates neuronal signaling in the etiology of
      obesity. Although the brain controls both energy intake and expenditure, it has
      more capacity to regulate energy intake rather than energy expenditure. In
      environments where food is abundant, this renders the body prone to weight
      increases. To gain more insight into the neurobiological mechanisms involved, we
      set out to investigate the effect of dietary exposure on the expression levels of
      obesity-associated genes in the ventro-medial hypothalamus (VMH)/arcuate nucleus
      (ARC) and the substantia nigra (SN)/ventral tegmental area (VTA), two brain
      regions that are implicated in feeding behavior. We show that the expression of
      Etv5, Faim2, Fto, Negr1 but not Sh2b1 is affected by nutritional state in these
      two areas, thereby providing insight into the relationship between nutritional
      state and expression levels of obesity-associated genes in two brain areas
      relevant to feeding.

PMID- 22627921
TI  - Covalently trapping MutS on DNA to study DNA mismatch recognition and signaling.
AB  - The DNA repair protein MutS forms clamp-like structures on DNA that search for
      and recognize base mismatches leading to ATP-transformed signaling clamps. In
      this study, the mobile MutS clamps were trapped on DNA in a functional state
      using single-cysteine variants of MutS and thiol-modified homoduplex or
      heteroduplex DNA. This approach allows stabilization of various transient MutS
      DNA complexes and will enable their structural and functional analysis.

PMID- 22627922
TI  - Direct visualization of CaMKII at postsynaptic densities by electron microscopy
      tomography.
AB  - Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) is a major component of
      postsynaptic densities (PSDs) involved in synaptic regulation. It has been
      previously shown that upon activity CaMKII from the spine reversibly aggregates
      at the cytoplasmic surfaces of PSDs, where it encounters various targets for
      phosphorylation. Targets for CaMKII are also present within the PSD, but there
      has been no reliable method to pinpoint whether, or where, CaMKII is located
      inside the PSD. Here we show that CaMKII can be mapped molecule-by-molecule
      within isolated PSDs using negative stain electron microscopy tomography. CaMKII
      molecules found in the core of the PSD may represent a pool distinct from the
      CaMKII residing at the cytoplasmic surface.

PMID- 22627923
TI  - Rapamycin treatment inhibits CHO cell death in a serum-free suspension culture by
      autophagy induction.
AB  - Rapamycin, a specific mTOR inhibitor, has been used as a chemical activator in
      autophagy research both in vitro and in vivo. Recently, autophagy has received
      attention as an anti-cell death engineering target in addition to apoptosis in
      the Chinese hamster ovary (CHO) cell engineering field. Here, the effect of
      rapamycin and the subsequent autophagy induction is investigated on two CHO cell
      lines, DG44 host and an antibody-producing recombinant CHO (rCHO), in a serum
      free suspension culture. In both cell lines, the rapamycin treatment delayed the
      viability drop and apoptosis induction. In particular, the improved cell
      viability of the antibody-producing rCHO cell line resulting from the rapamycin
      treatment led to a 21% increase in the maximum antibody concentration. From
      observations that a rapamycin derivative, everolimus, demonstrated similar
      positive effects in both cell lines, but not FK-506, which forms the same complex
      as rapamycin, but does not inhibit mTOR, it was demonstrated that the positive
      effects of rapamycin appear to be mTOR-dependent. In addition, the cultivation
      with rapamycin and/or an autophagy inhibitor, bafilomycin A1, indicated that the
      autophagy induction is related to the positive effects of rapamycin. The genetic
      perturbation of the autophagy pathway through the regulation of the expression
      level of Beclin-1, an important autophagy regulator, resulted in a delayed
      autophagy induction and apoptosis inhibition in response to the rapamycin
      treatment in the DG44 host cell line. Taken together, the results obtained in
      this study imply a positive role for autophagy and predict the usefulness of pro
      autophagy engineering in CHO cell cultures.

PMID- 22627925
TI  - Designer nanomaterials using chiral self-assembling peptide systems and their
      emerging benefit for society.
AB  - Chirality is absolutely central in chemistry and biology. The recent findings of
      chiral self-assembling peptides' remarkable chemical complementarity and
      structural compatibility make it one of the most inspired designer materials and
      structures in nanobiotechnology. The emerging field of designer chemistry and
      biology further explores biological and medical applications of these simple D,L-
      amino acids through producing marvellous nanostructures under physiological
      conditions. These self-assembled structures include well-ordered nanofibers,
      nanotubes and nanovesicles. These structures have been used for 3-dimensional
      tissue cultures of primary cells and stem cells, sustained release of small
      molecules, growth factors and monoclonal antibodies, accelerated wound-healing in
      reparative and regenerative medicine as well as tissue engineering. Recent
      advances in molecular designs have also led to the development of 3D fine-tuned
      bioactive tissue culture scaffolds. They are also used to stabilize membrane
      proteins including difficult G-protein coupled receptors for designing
      nanobiodevices. One of the self-assembling peptides has been used in human
      clinical trials for accelerated wound-healings. It is our hope that these peptide
      materials will open doors for more and diverse clinical uses. The field of chiral
      self-assembling peptide nanobiotechnology is growing in a number of directions
      that has led to many surprises in areas of novel materials, synthetic biology,
      clinical medicine and beyond.

PMID- 22627926
TI  - Why medical writing is important: a second look.

PMID- 22627924
TI  - The activity of the TRP-like channel depends on its expression system.
AB  - The Drosophila light activated TRP and TRPL channels have been a model for TRPC
      channel gating. Several gating mechanisms have been proposed following
      experiments conducted on photoreceptor and tissue cultured cells. However,
      conclusive evidence for any mechanism is still lacking. Here, we show that the
      Drosophila TRPL channel expressed in tissue cultured cells is constitutively
      active in S2 cells but is silent in HEK cells. Modulations of TRPL channel
      activity in different expression system by pharmacology or specific enzymes,
      which change the lipid content of the plasma membrane, resulted in conflicting
      effects. These findings demonstrate the difficulty in elucidating TRPC gating, as
      channel behavior is expression system dependent. However, clues on the gating
      mechanism may arise from understanding how different expression systems affect
      TRPC channel activation.

PMID- 22627927
TI  - A cheap and readily available assistant in hand surgery.
AB  - Controlling the digits during hand surgery can be challenging. During elective
      and emergency surgery, a "lead hand" can be used; however, during fracture
      surgery where an image intensifier is required, the lead hand prevents imaging.
      Sterile surgical gloves provide a cheap and readily available radiolucent
      alternative. The surgeon can use bands cut from the cuff of the glove. Performing
      procedures such as Kirschner wiring or plating of phalangeal fractures without an
      assistant become much easier with the use of this technique.

PMID- 22627928
TI  - Conservative management of ulnar tunnel syndrome: secondary to excessive healing
      tissue; a rare complication after flexor tendon injury--a case report.
AB  - The ulnar tunnel syndrome occurs usually from ganglions, lipoma, cysts, chronic
      repetitive trauma, bicycling, and the activities that require either prolonged
      wrist hyper extension or continued pressure on the hypothenar eminence. The ulnar
      tunnel syndrome after flexor tendon repair is a rare complication. We report on a
      24-year-old man with ulnar tunnel syndrome after a flexor tendon repair secondary
      to girder cut injury. The patient was managed conservatively for his hypertrophic
      scar for 9 weeks. After 9 weeks, the patient presented with no clawing and
      complete closure of the hand.

PMID- 22627929
TI  - Proximal row carpectomy with capitate osteochondral autograft transplantation.
AB  - Proximal row carpectomy (PRC) is an effective treatment option for degenerative
      or posttraumatic osteoarthritis of the wrist in conditions such as scapholunate
      advanced collapse, scaphoid nonunion advanced collapse, Kienbock disease, and
      chronic fracture dislocations of the carpus. PRC involves excision of the
      scaphoid, lunate, and triquetrum, and relies on the articulation of the remaining
      capitate from the distal row to articulate with the lunate fossa. PRC offers the
      potential advantage of greater range of motion, technical ease, and decreased
      immobilization, and eliminates specific complications found with other motion
      preserving procedures such as nonunion, hardware irritation, and impingement. An
      established relative contraindication for PRC is the presence of advanced
      capitolunate arthritis. Many authors have offered modifications of the
      traditional PRC procedure to account for the presence of capitate arthritis. A
      PRC technique utilizing an osteochondral autograft, from the carpal bank of
      excised bones, for transfer to the capitate defect is described.

PMID- 22627930
TI  - Fascial augmentation tenorrhaphy for extensor tendon lacerations in the forearm.
AB  - Proximal lacerations of the extensor tendon apparatus can pose a surgical
      challenge, especially when located at the musculotendinous junction or in
      patients presenting late. We describe a technique to augment the suture repair of
      these injuries utilizing local harvested strips of dorsal forearm fascia.

PMID- 22627931
TI  - Surgical technique of a radial wedge "camembert" osteotomy in Kienbock disease.
AB  - The main accepted principle to treat Kienbock disease is to decompress the
      lunate. Radius shortening is the most used technique. Three transverse
      osteotomies of the radius are described: neutral shortening osteotomy, lateral
      closing wedge osteotomy, and medial closing wedge osteotomy. Shortening the
      radius decompress the lunate and more or less the scaphoid. This deviates axial
      constraints toward ulna and triangular fibrocartilage complex. But the ulnar
      wrist is not able to support important axial constraints. The authors propose a
      solution to decompress only the lunate and not the scaphoid. This solution
      deviates axial constraints toward the scaphoid, which is naturally the most
      capable bone to support it. The authors describe a new radial nontransverse
      decompression wedge osteotomy. It allows to shorten the radius in front of the
      lunate. The fixation is done with a dorsal staple. To complete lunate
      decompression, authors propose to associate a metaphysal ulnar oblique
      shortening, essentially if ulnar variance is neutral or positive. The preliminar
      results on 10 cases are presented.

PMID- 22627932
TI  - Bicolumnar fusion for scaphoid nonunion advanced collapse without bone grafting.
AB  - Scaphoid nonunion advanced collapse leading to wrist osteoarthritis is treated by
      4-corner fusion, capitolunate arthrodesis, and 3-corner fusion with a variety of
      hardware and bone grafting techniques as reported in the literature. However,
      such procedures have been associated with complications such as nonunion,
      hardware failure, and deep infection. On the basis of the same concept of these
      intercarpal fusions with the aim to transmit the load of the wrist, we present
      bicolumnar fusion to fuse the capitolunate articulation and the triquetrohamate
      articulation and preserve the articulation between the 2 columns, maintaining
      much of the normal anatomy and physiology of the normal wrist. This technique has
      allowed the use of screws for compression of both articulations and achieve union
      without the use of bone grafting.

PMID- 22627933
TI  - Modified extensor carpi radialis brevis adductorplasty for ulnar nerve palsy.
AB  - Residual paralysis or irreparable injury to the ulnar nerve results in
      considerable impairment of hand function and posture that directly affect daily
      living. Usually, claw hand deformity and loss of key pinch become problematic,
      but tendon transfer can be used to restore the lost functions. Adductorplasty
      using a wrist extensor tendon can restore thumb adduction strength without a
      significant loss of wrist extension strength, but the short length of the wrist
      extensor necessitates a free tendon graft to reach the thumb. Here, the authors
      present a modified extensor carpi radialis brevis adductorplasty technique that
      does not need a tendon graft by elongating the tendinous portion.

PMID- 22627934
TI  - Unstable scaphoid nonunion treatment technique:  use of a volar distal radius
      corticocancellous autograft.
AB  - Scaphoid nonunions are challenging cases that first must be identified and then
      treated based on stability, collapse, and vascularity. Unstable nonunions are
      identified on the basis of collapse of the scaphoid into the "humpback" deformity
      with an increased intrascaphoid and scapholunate angles. The importance of
      restoring normal scaphoid alignment has been stressed, because failure to do so
      leads to worse clinical and radiographic results with predictable patterns of
      radiocarpal arthrosis. We present a technique to correct unstable scaphoid
      nonunions using a single volar-based incision with harvesting of volar distal
      radius corticocancellous autograft. This technique allows the avoidance of
      harvest site morbidity and has union rates comparable with the gold standard of
      iliac crest.

PMID- 22627935
TI  - Safe and easy method to preserve fingertip contour in VY-plasty.
AB  - VY-plasty is a well-known technique to reconstruct fingertip defects. A
      simplified method combining pinning of flap and healing of donor site by
      secondary intention is described. These steps preserve the rounded appearance of
      the fingertip and restore the convexity of the hyponychium. Flap ischemia due to
      suture-line tension is also averted.

PMID- 22627936
TI  - Anterior approach for operative fixation of coronoid fractures in complex elbow
      instability.
AB  - The coronoid process has been shown to play a critical role in ulnohumeral
      stability. Coronoid process fractures can occur in isolation or as part of a
      complex injury pattern. The most common complex pattern, known as the "terrible
      triad," includes a radial head fracture and elbow dislocation along with the
      coronoid fracture. Failure to address these fractures and ligamentous injuries
      can result in recurrent instability and progression to painful arthrosis. Both
      medial and lateral approaches to the coronoid have been popularized in recent
      literature, but there is no universally accepted approach. Common fixation
      techniques include suture lasso, suture anchors, lag screws, and plating all of
      which have various drawbacks. We describe a direct anterior approach to address
      coronoid process fractures made in addition to a lateral approach to address
      radial head and lateral collateral ligament injuries. Coronoid fractures
      addressed through the anterior approach were stabilized with anterior to
      posterior screw fixation combined with buttress plating, which allowed anatomic
      reduction and stable internal fixation at short-term follow-up.

PMID- 22627938
TI  - Wagner approach for first carpometacarpal joint denervation.
AB  - First carpometacarpal joint osteoarthritis is one of the most common conditions
      hand surgeons have to deal with. In this article, a more radical technique for
      joint denervation is presented as a treatment for painful degenerative or
      posttraumatic osteoarthritis. Moreover, a preliminary report of 18 cases treated
      with this technique is presented to support its benefits.

PMID- 22627937
TI  - A modification of the collar-and-cuff sling to elevate the hand.
AB  - Elevation of the hand is routinely sought after surgery and with pathology such
      as inflammation and infection. Many models of sling have been described. The
      collar-and-cuff model is a traditional low-cost method that is easily learned and
      applied, is versatile, and customized to each patient. It is, however, frequently
      misapplied so that it immobilizes the arm but does not produce sufficient
      elevation. We describe a minor modification that achieves high elevation while
      retaining all other advantages.

PMID- 22627939
TI  - Reverse digital artery flap from radial and ulnar borders of palm.
AB  - Reconstructing skin defects of the volar aspect of fingers can be a challenging
      task due to a lack of local expendable tissue. The reverse digital artery flap is
      a versatile and reliable technique that can be used to manage such disabling
      injuries. Various authors have used this flap effectively, but most have used the
      digit itself as the donor site. This limits the size of the flap and also
      necessitates skin grafting to cover the donor site. Large reverse digital artery
      flaps can be raised from the radial and ulnar borders of the palm facilitating
      coverage of significant digital defects and primary closure of the donor site,
      resulting in minimal donor-site morbidity. We describe 3 illustrative cases to
      highlight the flaps versatility.

PMID- 22627940
TI  - A palmar approach for insertion of a free, nonvascularized phalangeal transfer.
AB  - Free nonvascularized phalangeal transfer from a toe to congenitally hypoplastic
      digits, is an established procedure in the repertoire of digit reconstruction.
      The hypoplastic digit is frequently flexed, due to shortage of palmar soft
      tissues. The phalanx must be transferred intact, with a complete periosteal
      covering. A new technique of incision and dissection is described utilizing a
      palmar V approach, closed after skin advancement, as a Y. This permits ample
      visualization of the digital envelope to receive the phalanx, protection under
      direct vision of the digital bundles, and simultaneous correction of the
      deficient palmar skin, without tension.

PMID- 22627943
TI  - The involvement of Notch signaling in melanoma vasculogenic mimicry.
AB  - Notch signaling plays an important role in tumor angiogenesis. Recent studies
      suggest that Notch signaling also regulates the progression of primary melanomas
      toward an aggressive phenotype. The aim of this study was to investigate the
      involvement of Notch signaling pathway in organization of tumor cells into
      capillary-like structures (CLS), the phenomenon also known as vasculogenic
      mimicry (VM). Here, we show that Notch signaling cascade was constitutively
      active in melanoma cell lines we used. Blocking Notch signaling with the gamma
      secretase inhibitors, DAPT, dibenzazepine or Jagged1 neutralizing antibody
      resulted in stabilization of CLS indicating that Notch signaling pathway
      attenuates melanoma VM. We further studied this phenomenon on melanomas grafted
      in nude mice. Compared to control, VM channels in DAPT-treated grafted melanoma
      became larger and more branched. DAPT-treated melanomas also exhibited an up
      regulation of MMP-2 and VEGFR1, both known as VM mediators. Moreover, we did not
      observe necrosis in VM channels areas of DAPT-treated melanomas. These findings
      indicate that VM regulated by Notch signaling may present a novel target in
      melanoma therapy. 

PMID- 22627944
TI  - T2* mapping of acetabular and femoral hip joint cartilage at 3 T: a prospective
      controlled study.
AB  - OBJECTIVES: The aim of this study was to identify the pattern of T2* values in
      acetabular and femoral head cartilage in morphologically normal and abnormal
      zones at 3 T. MATERIALS AND METHODS: Twenty-nine patients (mean [SD] age, 30.8
      [8.8] years) with symptomatic femoroacetabular impingement and suspected
      cartilage damage (study group) and 35 healthy, asymptomatic volunteers (mean [SD]
      age, 24.9 [2.1] years) with no obvious history of hip diseases or abnormalities
      (control group) were included. Magnetic resonance imaging was performed at 3 T
      using a 3-dimensional (3D) double-echo steady-state sequence for grading
      cartilage morphologically and a 3D multiecho data image combination sequence for
      T2* assessment. Statistical assessment included the Student t test to reveal
      differences between mean T2* values of the study group and the control group. One
      way analysis of variance was used to identify any statistically significant
      differences between the T2* values in various grades (modified Outerbridge score
      system) of cartilage damage within the study group. RESULTS: Significant
      differences were noted between the T2* values in the study group and the control
      group (P < 0.001). We also noted a significant drop in T2* in accordance with the
      morphologic damage in the study group (P < 0.001). The largest drop in T2* was
      found between morphologically normal-appearing cartilage (grade 0; T2*, 25.2
      milliseconds) and grade I changes (T2*, 18.1 milliseconds) (P < 0.001).
      CONCLUSIONS: In combination with a 3-T system, T2* mapping offers unique
      advantages such as high image resolution and the ability of 3D biochemically
      sensitive cartilage evaluation in the hip joint without the need for contrast
      medium. Given these advantages, we believe that T2* mapping is another welcome
      addition to the rapidly evolving era of hip cartilage biochemical imaging.
      Further studies are necessary that involve a diagnostic histological analysis as
      gold standard for comparison.

PMID- 22627945
TI  - Three-dimensional imaging of the aortic vessel wall using an elastin-specific
      magnetic resonance contrast agent.
AB  - OBJECTIVE: The aim of this study was to demonstrate the feasibility of high
      resolution 3-dimensional aortic vessel wall imaging using a novel elastin
      specific magnetic resonance contrast agent (ESMA) in a large animal model.
      MATERIALS AND METHODS: The thoracic aortic vessel wall of 6 Landrace pigs was
      imaged using a novel ESMA and a nonspecific control agent. On day 1, imaging was
      performed before and after the administration of a nonspecific control agent,
      gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA; Bayer Schering AG,
      Berlin, Germany). On day 3, identical scans were repeated before and after the
      administration of a novel ESMA (Lantheus Medical Imaging, North Billerica,
      Massachusetts). Three-dimensional inversion recovery gradient echo delayed
      enhancement imaging and magnetic resonance (MR) angiography of the thoracic
      aortic vessel wall were performed on a 1.5-T MR scanner (Achieva; Philips Medical
      Systems, the Netherlands). The signal-to-noise ratio and the contrast-to-noise
      ratio of arterial wall enhancement, including the time course of enhancement,
      were assessed for ESMA and Gd-DTPA. After the completion of imaging sessions,
      histology, electron microscopy, and inductively coupled plasma mass spectroscopy
      were performed to localize and quantify the gadolinium bound to the arterial
      vessel wall. RESULTS: Administration of ESMA resulted in a strong enhancement of
      the aortic vessel wall on delayed-enhancement imaging, whereas no significant
      enhancement could be measured with Gd-DTPA. Ninety to 100 minutes after the
      administration of ESMA, significantly higher signal-to-noise ratio and contrast
      to-noise ratio could be measured compared with the administration of Gd-DTPA
      (45.7 +/- 9.6 vs 13.2 +/- 3.5, P < 0.05 and 41.9 +/- 9.1 vs 5.2 +/- 2.0, P <
      0.05). A significant correlation (0.96; P < 0.01) between area measurements
      derived from ESMA scans and aortic MR angiography scans could be found. Electron
      microscopy and inductively coupled plasma mass spectroscopy confirmed the
      colocalization of ESMA with elastic fibers. CONCLUSION: We demonstrate the
      feasibility of aortic vessel wall imaging using a novel ESMA in a large animal
      model under conditions resembling a clinical setting. Such an approach could be
      useful for the fast 3-dimensional assessment of the arterial vessel wall in the
      context of atherosclerosis, aortic aneurysms, and hypertension.

PMID- 22627946
TI  - A unique substituted Co(II)-formate coordination framework exhibits weak
      ferromagnetic single-chain-magnet like behavior.
AB  - A magnetic isolated chain-based substituted cobalt-formate framework was obtained
      with isonicotine as a spacer. In the chain, canted antiferromagnetic interactions
      exist in between the Co(II) ions, and slow magnetic relaxation is detected at low
      temperature. For the block effects of the isonicotine ligands, the complex could
      be considered as a peculiar example of a weak ferromagnetic single-chain-magnet.

PMID- 22627947
TI  - Percutaneous cannulated screw fixation in the treatment of distal radius
      fractures.
AB  - PURPOSE: The aim of this study was to determine the results of closed reduction
      and percutaneous fixation of distal radial fractures with standard 4.0-mm
      cannulated screw. METHODS: We collected prospective outcomes data for 20 patients
      between 18 and 60 years of age (mean 39) with acute, displaced, extraarticular
      and unstable fractures of the distal radius treated with closed reduction,
      percutaneous cannulated screw fixation and early mobilization. The visits at
      months 2, 6 and 12 were specified as index follow-up visits and assessments of
      motion, grip strength and standard radiographs were performed. The Gartland
      Werley functional scores and the Disabilities of the Arm, Shoulder and Hand
      (QuickDASH) scores were recorded. RESULTS: Mean values of flexion, extension,
      pronation and supination on the injured side were up to 70 % of those on the
      uninjured side at 2 months postoperatively. By 12 months, range of motion values
      on the injured side showed continuous and significant improvement and flexion,
      extension, pronation, supination and ulnar deviation reached up to 90 % of those
      on the uninjured side. A large and significant improvement was seen from 2 to 6
      months in the QuickDASH score. A smaller improvement was seen from 6 to 12
      months, which was judged not to be significant. Radiographic values were close to
      anatomic parameters, and the alignment was maintained at 12 months follow-up. No
      complications occurred. CONCLUSIONS: Cannulated screw fixation appears to be an
      effective means of allowing immediate range of motion of the wrist, resulting in
      a rapid and comfortable functional recovery while maintaining alignment to bone
      healing.

PMID- 22627948
TI  - Network meta-analysis of prasugrel, ticagrelor, high- and standard-dose
      clopidogrel in patients scheduled for percutaneous coronary interventions.
AB  - Since novel antiplatelet treatments (prasugrel, ticagrelor, high-dose
      clopidogrel) have been predominantly tested against standard-dose clopidogrel,
      data on direct comparisons between these therapies are scarce. We therefore
      indirectly compared their efficacy and safety in patients undergoing percutaneous
      coronary intervention. Electronic databases were searched systematically to
      identify head-to-head randomised controlled trials (RCTs). Network meta-analysis
      was performed using generalised linear mixed models with adjustment for length of
      follow-up. Findings were corroborated by mixed treatment comparison through
      Bayesian methods. Fourteen RCTs were identified and included in the analysis
      (high- vs. standard-dose clopidogrel: 9 trials, prasugrel vs. high-dose
      clopidogrel: 2 trials, prasugrel vs. standard-dose clopidogrel: 2 trials,
      ticagrelor vs. standard-dose clopidogrel: 1 trial). No significant differences
      were found for efficacy outcomes except for stent thrombosis favouring prasugrel
      (vs. ticagrelor: odds ratio [OR] 0.63, 95% confidence interval [CI]: 0.42, 0.94;
      vs. high-dose clopidogrel: OR 0.70, 95%CI: 0.48, 1.01). Prasugrel exhibited a
      similar bleeding risk as high-dose clopidogrel, but more major (OR 1.43, 95%CI
      1.07, 1.90) and major or minor bleeding (OR 1.36, 95%CI 1.09, 1.69) compared to
      ticagrelor. Ticagrelor was also associated with less major or minor bleeding
      compared to high-dose clopidogrel (OR 0.81, 95%CI 0.69, 0.96). No differences
      were seen for non CABG-related major bleeding between the three strategies.
      Results were corroborated in a subgroup analysis comprising only patients with
      acute coronary syndromes. In the absence of head-to-head clinical trials, network
      meta-analysis suggests potentially relevant differences in efficacy and bleeding
      risk among novel antiplatelet treatments and may thereby advance understanding of
      their differential therapeutic properties.

PMID- 22627953
TI  - Resection of a giant, invasive malignant solitary fibrous tumor of pleura.
AB  - Solitary fibrous tumor of pleura (SFTP) is a rare mesenchymal neoplasm that most
      commonly involves the pleura, is probably derived from fibroblasts, and has no
      relationship to malignant mesothelioma. Here, we report a case of complete
      resection of a giant malignant SFTP. A 61-year-old woman developed fever and left
      flank pain. Computed tomography revealed the tumor to be 13 cm in size and
      located in the left thoracic cavity, directly invading the left lower lobe of the
      lung. The patient underwent radical resection and left lower lobectomy.
      Immunohistochemical examination revealed a dense proliferation of spindle-shaped
      cells with ovoid nuclei and collagen fibers hyperplasia. The cells were positive
      for CD34 and vimentin, and were negative for cytokeratin AE1/AE3, calretinin, S
      100 and smooth muscle alpha-actin. SFTPs have malignant potential, as 20-30 % of
      resected SFTPs reportedly contain malignant components. Careful long-term
      clinical follow-up is therefore required for all cases of SFTP.

PMID- 22627954
TI  - A case of intravenous leiomyomatosis of uterine origin, extending through the
      inferior vena cava to right atrium.
AB  - Intravenous leiomyomatosis (IVL) is a rare benign tumor that originates from
      uterus, and sometimes extends to the right heart. We report a case of IVL that
      extended to right atrium through the inferior vena cava (IVC) which was resected
      using partial cardiopulmonary bypass. Multi detector computed tomography and
      ultrasound played a vital role in arriving at the diagnosis. Complete resection
      of tumor in the heart and great vein, and separation of the tumor stump from the
      IVC are essential in the treatment of IVL.

PMID- 22627955
TI  - Surgical correction of giant extracardiac unruptured aneurysm of the right
      coronary sinus of Valsalva: case report and review of the literature.
AB  - We report a quite rare case of giant extracardiac unruptured aneurysm of the
      right coronary sinus of Valsalva with no clinical findings of Marfan syndrome or
      Ehlers-Danlos syndrome. A 52-year-old Chinese male was diagnosed having an
      aneurysm of the right sinus of Valsalva and moderate aortic regurgitation, while
      Bentall operation was performed successfully. The patient was discharged with no
      complications. Pathological examination revealed conspicuously medial mucoid
      degeneration of the aneurismal wall and absence of medial elastic fibers.
      Immediate results and early follow-up were uneventful.

PMID- 22627956
TI  - Pulmonary aspergilloma: a potential cause of false positive fluorodeoxyglucose
      positron emission tomography scan.
AB  - Pulmonary aspergilloma is a fungus ball developed in a pre-existing lung cavity,
      generally in the superior lobes. Its size remains stable in most cases and it is
      usually asymptomatic. Herein, we present a case of a 64-year-old male with
      pulmonary aspergilloma, which was developed in an emphysematous cyst of the right
      inferior lobe, increased in size, and fluorodeoxyglucose positron emission
      tomography scan was positive. There are only a few reported cases of pulmonary
      aspergilloma with a false positive fluorodeoxyglucose positron emission
      tomography scan.

PMID- 22627957
TI  - Death due to undetected heparin-induced thrombocytopenia after cardiac surgery.
AB  - A 41-year-old male patient was diagnosed acute myocardial infarction. An intra
      aortic balloon pump was inserted to treat heart failure, and off-pump coronary
      artery bypass surgery was performed. Postoperative cardiac catheterization
      revealed occlusion of all the 3 bypass grafts, and percutaneous coronary
      intervention (PCI) was performed. Thrombosis due to heparin-induced
      thrombocytopenia (HIT) occurred during PCI, which was completed after switching
      to argatroban based on the possible HIT. Cardiopulmonary arrest occurred suddenly
      after PCI, and the patient died. Undetected HIT may have caused the sudden
      change. HIT should be suspected and aggressively treated when thrombocytopenia
      occurs even during assisted circulation.

PMID- 22627958
TI  - Pulmonary botryomycosis on a lung cavity: a rare pulmonary infection mimicking
      cancer.
AB  - Lung botryomycosis is a rare disease. We report what is to our knowledge the
      first case occurring on a lung cavity. In a 42-year-old man suffering asthenia
      and cough, a chest radiograph revealed a right upper lobe opacity. Computed
      tomography scan showed a necrotic mass which was also spiculated. Repeated
      research for Mycobacterium tuberculosis was negative. The patient underwent a
      lobectomy. Histological and bacteriological examinations made the diagnosis of
      botryomycosis, because the cavity presented numerous colonies of pyogenic
      Fusobacterium nucleatum bacteria. Botryomycosis is a difficult diagnosis that
      clinically mimics actinomycosis, tuberculosis or cancer. In most cases, surgery
      is necessary to assess diagnosis and treatment.

PMID- 22627959
TI  - Re-expansion pulmonary edema in a patient with total pneumothorax: a hazardous
      outcome.
AB  - Re-expansion pulmonary edema (REPE) is a rare complication of treatment of
      spontaneous pneumothorax or large pleural effusions. As a complication of
      spontaneous pneumothorax treatment, only few cases are documented, and even fewer
      document the role of non-invasive continuous positive airway pressure mechanical
      ventilation for treatment of this rare entity. We present a case of 23-year-old
      man who presented with left-sided pneumothorax, developed unilateral REPE and was
      treated with non-invasive continuous positive airway pressure.

PMID- 22627960
TI  - Surgical treatment for acute type A aortic dissection during pregnancy (16 weeks)
      with Loeys-Dietz syndrome.
AB  - A 32-year-old woman at 16 weeks of pregnancy was diagnosed with acute type A
      aortic dissection and severe aortic regurgitation. Aortic valve and aortic arch
      replacement was successfully performed under circulatory arrest with deep
      hypothermia. After the operation, she was diagnosed with Loeys-Dietz syndrome. At
      36 weeks of gestation, the patient underwent a cesarean section and delivered a
      healthy baby.

PMID- 22627961
TI  - Cardiac herniation after operative management of lung cancer: a rare and
      dangerous complication.
AB  - Cardiac herniation after pneumonectomy is recognized as a rare complication. This
      case report describes two cases. The mortality rate of this complication remains
      high as reported in the literature; in early-recognized cases 50 % and in late or
      unrecognized cases 100 %. In the following two cases a pneumonectomy was
      performed as a treatment for lung cancer. Within 48 h after the initial operative
      treatment, the clinical situation of the patients got worse and radiographic
      examinations showed a strongly deviated heart. After suspicion of the diagnosis,
      the patients were immediately transferred to the operation theatre for emergency
      thoracotomy. Per-operative the diagnosis was confirmed and the heart was returned
      into its original position while the defect in the pericardial sac was closed
      with a bovine pericardial patch. Both patients survived these procedures and did
      not suffer from any further complication.

PMID- 22627962
TI  - Late, giant brachial artery aneurysm following hemodialysis fistula ligation in a
      renal transplant patient: case report and literature review.
AB  - Brachial artery aneurysm (BAA) following long-standing arteriovenous fistula
      ligation after renal transplantation is uncommon. Herein, we describe the case of
      a 64-year-old man who developed a giant symptomatic BAA 21 years after ligation
      of the fistula. He was submitted to surgical excision of the aneurysm followed by
      interposition prosthetic graft.

PMID- 22627963
TI  - Completely resected superior sulcus tumor and vascular reconstruction of
      vertebral and subclavian arteries.
AB  - A 62-year-old man was pointed out the superior sulcus tumor of the left lung
      invading to the subclavian artery and the vertebral artery. Bronchoscopic
      brushing cytology of the tumor showed Class V large cell carcinoma. The patient
      was diagnosed as clinical stage IIIA(cT4N0M0). After concurrent
      chemoradiotherapy, we performed left-upper lobectomy and reconstructions of left
      subclavian and vertebral arteries through modified transmanubrial approach.
      Surgeons of three different departments took part in the operation. Cooperative
      works were the key for the complete resection of such an advanced superior sulcus
      tumor.

PMID- 22627964
TI  - Pulmonary carcinosarcoma with an osteosarcomatous component.
AB  - Pulmonary carcinosarcoma is a rare disease entity defined as a neoplasm, which
      has biphasic features consisting of both epithelial and sarcomatous components.
      It has been reported that the most frequent epithelial component is squamous cell
      carcinoma, while the most frequent sarcomatous component is rhabdomyosarcoma.
      Pulmonary carcinosarcomas with osteosarcoma components are even rarer. We report
      a case of a potentially curative resection for carcinosarcoma with an
      osteosarcoma component. Thoracic surgeons should be aware of this rare tumor when
      lung tumors with ossification are encountered.

PMID- 22627965
TI  - Severe MRSA necrotizing pneumonia.

PMID- 22627966
TI  - Enhanced refocusing of fat signals using optimized multipulse echo sequences.
AB  - Endogenous magnetic resonance contrast based on the localized composition of fat
      in vivo can provide functional information. We found that the unequal pulse
      timings of the Uhrig's dynamical decoupling multipulse echo sequences
      significantly alter the signal intensity compared to conventional, equal-spaced
      Carr-Purcell-Meiboom-Gill sequences. The signal increases and decreases depending
      on the tissue and sequence parameters, as well as on the interpulse spacings;
      particularly strong differences were observed in fatty tissues, which have a
      highly structured morphology and a wide range of chemical shifts and J-couplings.
      We found that the predominant mechanism for fat refocusing under multipulse echo
      sequences is the chemical structure, with stimulated echoes playing a pivotal
      role. As a result, specialized pulse sequences can be designed to optimize
      refocusing of the fat chemical shifts and J-couplings, where the degree of
      refocusing can be tailored to specific types of fats. To determine the optimal
      time delays, we simulated various Uhrig dynamical decoupling and Carr-Purcell
      Meiboom-Gill pulse sequence timings, and these results are compared to
      experimental results obtained on excised and in vivo fatty tissue. Applications
      to intermolecular multiple quantum coherence imaging, where the improved echo
      refocusing translates directly into signal enhancements, are presented as well.

PMID- 22627967
TI  - The serological profile of fondaparinux-associated heparin-induced
      thrombocytopenia syndrome.

PMID- 22627968
TI  - Using the flexible ligand bis(2-hydroxyethyl)amino-tris (hydroxymethyl)methane
      ("bis-tris") to access a family of 3d-4f Mn(III)4Ln4 complexes.
AB  - A series of isostructural 3d-4f coordination clusters (CCs)
      [Mn(4)Ln(4)(OH)(6)(H(2)L)(2)(H(3)L)(2)(PhCO(2))(2)(N(3))(2)(MeOH)(4)]Cl(1.6)(N(3)
      (0.4)(NO(3))(2).2.4H(2)O.1.6MeOH where Ln = Gd, Tb, Dy, Ho and Er and H(5)L =
      bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane (bis-tris) has been
      synthesised and structurally characterised. The paramagnetic metal ions within
      the clusters are weakly antiferromagnetically coupled, with the Tb and Dy
      compounds displaying slow relaxation of their magnetisation. This is the first
      report of this versatile ligand being used to target 3d-4f CCs.

PMID- 22627970
TI  - The role of octopamine and tyramine in Drosophila larval locomotion.
AB  - The characteristic crawling behavior of Drosophila larvae consists of a series of
      rhythmic waves of peristalsis and episodes of head swinging and turning. The two
      biogenic amines octopamine and tyramine have recently been shown to modulate
      various parameters of locomotion, such as muscle contraction, the time spent in
      pausing or forward locomotion, and the initiation and maintenance of rhythmic
      motor patterns. By using mutants having altered octopamine and tyramine levels
      and by genetic interference with both systems we confirm that signaling of these
      two amines is necessary for larval locomotion. We show that a small set of about
      40 octopaminergic/tyraminergic neurons within the ventral nerve cord is
      sufficient to trigger proper larval locomotion. Using single-cell clones, we
      describe the morphology of these neurons individually. Given various potential
      roles of octopamine and tyramine in the larval brain, such as locomotion,
      learning and memory, stress-induced behaviors or the regulation of the energy
      state, functions that are often not easy to discriminate, we dissect here for the
      first time a subset of this complex circuit that modulates specifically larval
      locomotion. Thus, these data will help to understand-for a given neuronal
      modulator-how specific behavioral functions are executed within distinct
      subcircuits of a complex neuronal network.

PMID- 22627969
TI  - Randomized clinical trial of ultrasound-guided foam sclerotherapy versus surgery
      for the incompetent great saphenous vein.
AB  - BACKGROUND: New minimally invasive treatment modalities, such as ultrasound
      guided foam sclerotherapy (UGFS), are becoming more popular. In a multicentre
      randomized controlled non-inferiority trial, the effectiveness and costs of UGFS
      and surgery for treatment of the incompetent great saphenous vein (GSV) were
      compared. METHODS: Patients with primary great saphenous varicose veins were
      assigned randomly to either UGFS or surgical stripping with high ligation.
      Recurrence, defined as reflux combined with venous symptoms, was determined on
      colour duplex scans at baseline, 3 months, 1 year and 2 years after initial
      treatment. Secondary outcomes were presence of recurrent reflux (irrespective of
      symptoms), reduction of symptoms, health-related quality of life (EQ-5D(TM)),
      adverse events and direct hospital costs. RESULTS: Two hundred and thirty
      patients were treated by UGFS and 200 underwent GSV stripping. The 2-year
      probability of recurrence was similar in the UGFS and surgery groups: 11.3 per
      cent (24 of 213) and 9.0 per cent (16 of 177) respectively (P = 0.407). At 2
      years, reflux irrespective of venous symptoms was significantly more frequent in
      the UGFS group (35.0 per cent) than in the surgery group (21.0 per cent) (P =
      0.003). Mean(s.d.) hospital costs per patient over 2 years were ?774(344) per
      patient for UGFS and ?1824(141) for stripping. CONCLUSION: At 2-year follow-up,
      UGFS was not inferior to surgery when reflux associated with venous symptoms was
      the clinical outcome of interest. UGFS has the potential to be a cost-effective
      approach to a common health problem. Registration numbers: NCT01103258
      (http://www.clinicaltrials.gov) and NTR654 (http://www.trialregister.nl).

PMID- 22627971
TI  - Chemical constituents of the ethyl acetate extract of Belamcanda chinensis (L.)
      DC roots and their antitumor activities.
AB  - An activity-directed fractionation and purification process was used to isolate
      antitumor compounds from the roots of Belamcanda chinensis (L.) DC. The ethyl
      acetate extract showed greater antitumor activities than the other extracts,
      consequently leading to the isolation of 18 compounds identified as beta
      sitosterol (1), dausterol (2), quercetin (3), kampferol (4), shikimic acid (5),
      gallic acid (6), ursolic acid (7), betulin (8), betulonic acid (9), betulone
      (10), tectoridin (11), irisflorentin (12), 4',5,6-trihydroxy-7-methoxyisoflavone
      (13), tectorigenin (14), irilins A (15), iridin (16), irigenin (17), and
      iristectongenin A (18). Compounds 3-10, 13, and 15 were isolated from B.
      chinensis for the first time. Compounds 4 and 7-10 showed potent cytotoxic
      activities against PC3, MGC-803, Bcap-37, and MCF-7 cell lines. The mechanism of
      the antitumor action of compound 7 was preliminarily investigated through
      acridine orange/ethidium bromide (AO/EB) staining, Hoechst 33258 staining, and
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, which
      indicated the growth inhibition of MGC-803 cells via the induction of tumor cell
      apoptosis.

PMID- 22627972
TI  - Chiral bis(imidazolidine)pyridine-cu complex-catalyzed enantioselective [3+2]
      cycloaddition of azomethine imines with propiolates.
AB  - [3+2] Cycloaddition of azomethine imines with electron-deficient terminal alkynes
      was smoothly catalyzed by a chiral bis(imidazolidine)pyridine-CuOAc complex to
      give bicyclic pyrazolo[1,2-a]pyrazolone derivatives with up to 74% ee.

PMID- 22627974
TI  - Swan song.

PMID- 22627975
TI  - A better index of body adiposity.

PMID- 22627976
TI  - Cystatin C may better reflect the effect of obesity on renal function.

PMID- 22627977
TI  - Weak relationship of intraperitoneal fat volume with ascending aortic wall
      thickness.

PMID- 22627978
TI  - Another (better) index of adiposity.

PMID- 22627979
TI  - Newly proposed body adiposity index (bai) by Bergman et al. is not strongly
      related to cardiovascular health risk.

PMID- 22627980
TI  - BMI Correlates Better to Visceral Fat and Insulin Sensitivity Than BAI.

PMID- 22627981
TI  - Impact of atrial fibrillation on outcome in thrombolyzed patients with stroke:
      evidence from the Virtual International Stroke Trials Archive (VISTA).
AB  - BACKGROUND AND PURPOSE: Atrial fibrillation has been considered a risk factor for
      poor outcome from acute stroke and may influence response to thrombolysis,
      although supporting data are limited due to potential confounding with age and
      stroke severity. METHOD: We assessed the association of atrial fibrillation and
      thrombolysis exposure with the modified Rankin Scale score distribution at 90
      days among patients registered in a trials archive. We used an age and baseline
      National Institutes of Health Stroke Scale-adjusted Cochran-Mantel-Haenszel test
      to test significance (P) followed by proportional odds logistic regression
      analysis to estimate the ORs for improved modified Rankin Scale score. RESULTS:
      Data were available for 7091 patients, of whom 3027 were thrombolyzed. A total of
      1631 patients had a history of atrial fibrillation, of whom 639 were
      thrombolyzed. Among patients with atrial fibrillation, baseline severity was
      greater (median baseline National Institutes of Health Stroke Scale, 14 versus
      12; P<0.001) and age was higher (mean age, 74.0 versus 66.5; P<0.001). An
      association of treatment with outcome was seen independently and was of similar
      magnitude within patients with atrial fibrillation (OR, 1.44; 95% CI, 1.12-1.73;
      P<0.001) and without atrial fibrillation (OR, 1.53; 95% CI, 1.39-1.69; P<0.001).
      No association of atrial fibrillation and overall stroke outcome could be found
      (OR, 0.93; 95% CI, 0.84-1.03; P=0.409). CONCLUSIONS: In this nonrandomized
      comparison, presence of atrial fibrillation had no independent impact on stroke
      outcome and compared with untreated comparators, the patients who received
      thrombolysis experienced an advantage in outcomes that was of equal magnitude
      whether in the presence or absence of atrial fibrillation.

PMID- 22627982
TI  - Letter by Maarsingh and van der Wouden regarding article, "Application of the
      ABCD2 score to identify cerebrovascular causes of dizziness in the emergency
      department".

PMID- 22627983
TI  - Effects of telerehabilitation on physical function and disability for stroke
      patients: a randomized, controlled trial.
AB  - BACKGROUND AND PURPOSE: To determine the effect of a multifaceted stroke
      telerehabilitation (STeleR) intervention on physical function, and secondarily on
      disability, in veterans poststroke. METHODS: We conducted a prospective,
      randomized, multisite, single-blinded trial in 52 veterans with stroke from 3
      Veterans Affairs medical centers. Veterans with a stroke in the preceding 24
      months were randomized to the STeleR intervention or usual care. The STeleR
      intervention consisted of 3 home visits, 5 telephone calls, and an in-home
      messaging device provided over 3 months to instruct patients in functionally
      based exercises and adaptive strategies. Usual care participants received routine
      rehabilitation care as prescribed by their physicians. The primary outcome
      measures were improvement in function at 6 months, measured by both the motor
      subscale of the Telephone Version of Functional Independence Measure and by the
      function scales of the Late-Life Function and Disability Instrument. RESULTS: The
      2 complementary primary outcomes (Late-Life Function and Disability Instrument
      Function and Telephone Version of Functional Independence Measure) improved at 6
      months for the STeleR group and declined for the usual care group, but the
      differences were not statistically significant (P=0.25, Late-Life Function and
      Disability Instrument; P=0.316). Several of secondary outcomes were statistically
      significant. At 6 months, compared with the usual care group, the STeleR group
      showed statistically significant improvements in 4 of the 5 Late-Life Function
      and Disability Instrument disability component subscales (P<0.05), and approached
      significance in 1 of the 3 Function component subscales (P=0.06). CONCLUSIONS:
      The STeleR intervention significantly improved physical function, with
      improvements persisting up to 3 months after completing the intervention. STeleR
      could be a useful supplement to traditional poststroke rehabilitation given the
      limited resources available for in-home rehabilitation for stroke survivors.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00384748.

PMID- 22627985
TI  - Cost avoidance associated with optimal stroke care in Canada.
AB  - BACKGROUND AND PURPOSE: Evidence-based stroke care has been shown to improve
      patient outcomes and may reduce health system costs. Cost savings, however, are
      poorly quantified. This study assesses 4 aspects of stroke management (rapid
      assessment and treatment services, thrombolytic therapy, organized stroke units,
      and early home-supported discharge) and estimates the potential for cost
      avoidance in Canada if these services were provided in a comprehensive fashion.
      METHODS: Several independent data sources, including the Canadian Institute of
      Health Information Discharge Abstract Database, the 2008-2009 National Stroke
      Audit, and the Acute Cerebrovascular Syndrome Registry in the province of British
      Columbia, were used to assess the current status of stroke care in Canada.
      Evidence from the literature was used to estimate the effect of providing optimal
      stroke care on rates of acute care hospitalization, length of stay in hospital,
      discharge disposition (including death), changes in quality of life, and costs
      avoided. RESULTS: Comprehensive and optimal stroke care in Canada would decrease
      the number of annual hospital episodes by 1062 (3.3%), the number of acute care
      days by 166 000 (25.9%), and the number of residential care days by 573 000
      (12.8%). The number of deaths in the hospital would be reduced by 1061 (14.9%).
      Total avoidance of costs was estimated at $682 million annually ($307.4 million
      in direct costs, $374.3 million in indirect costs). CONCLUSIONS: The costs of
      stroke care in Canada can be substantially reduced, at the same time as improving
      patient outcomes, with the greater use of known effective treatment modalities.

PMID- 22627984
TI  - Poststroke disposition and associated factors in a population-based study: the
      Dijon Stroke Registry.
AB  - BACKGROUND AND PURPOSE: The organization of poststroke care will be a major
      challenge in coming years. We aimed to assess hospital disposition after stroke
      and its associated factors in clinical practice. METHODS: All cases of stroke
      from 2006 to 2010 were identified from the population-based Stroke Registry of
      Dijon, France. Demographic features, risk factors, and prestroke treatments were
      recorded. Admission stroke severity was assessed using the National Institutes of
      Health Stroke Scale score. At discharge, we collected dementia, disability using
      the modified Rankin Scale, length of stay, and hospital disposition (home,
      rehabilitation, convalescent home, and nursing home). Multivariate analyses were
      performed using logistic regression models to identify associated factors of
      postdischarge disposition. RESULTS: Of the patients with 1069 stroke included,
      913 survived acute care. Among them, 433 (47.4%) returned home, whereas 206
      (22.6%) were discharged to rehabilitation, 134 (14.7%) were admitted to a
      convalescent home, and 140 (15.3%) to a nursing home. Old patients, those under
      anticoagulants before stroke, those with severe stroke on admission, severe
      disability at discharge, dementia, or prolonged length of stay were less likely
      to return home. Moreover, advanced age, severe initial stroke, severe disability
      at discharge, and dementia were associated with admission to convalescent and
      nursing homes rather than rehabilitation centers. CONCLUSION: This population
      based study demonstrated that postdischarge destinations are associated with
      several factors. Our findings may be useful to establish health policy concerning
      the organization of poststroke care.

PMID- 22627986
TI  - Head and neck cooling decreases tympanic and skin temperature, but significantly
      increases blood pressure.
AB  - BACKGROUND AND PURPOSE: Localized head and neck cooling might be suited to induce
      therapeutic hypothermia in acute brain injury such as stroke. Safety issues of
      head and neck cooling are undetermined and may include cardiovascular autonomic
      side effects that were identified in this study. METHODS: Ten healthy men (age
      35+/-13 years) underwent 120 minutes of combined head and neck cooling (Sovika,
      HVM Medical). Before and after onset of cooling, after 60 and 120 minutes, we
      determined rectal, tympanic, and forehead skin temperatures, RR intervals,
      systolic and diastolic blood pressures (BP), laser-Doppler skin blood flow at the
      index finger and cheek, and spectral powers of mainly sympathetic low-frequency
      (0.04-0.15 Hz) and parasympathetic high-frequency (0.15-0.5 Hz) RR interval
      oscillations and sympathetic low-frequency oscillations of BP. We compared values
      before and during cooling using analysis of variance with post hoc analysis;
      (significance, P<0.05). RESULTS: Forehead skin temperature dropped by 5.5+/-2.2
      degrees C with cooling onset and by 12.4+/-3.2 degrees C after 20 minutes.
      Tympanic temperature decreased by 4.7+/-0.7 degrees C within 40 minutes, and
      rectal temperature by only 0.3+/-0.3 degrees C after 120 minutes. Systolic and
      diastolic BP increased immediately on cooling onset and rose by 15.3+/-20.8 mm Hg
      and 16.5+/-13.4 mm Hg (P=0.004) after 120 minutes, whereas skin blood flow fell
      significantly during cooling. RR intervals and parasympathetic RR interval high
      frequency powers increased with cooling onset and were significantly higher after
      60 and 120 minutes than they were before cooling. CONCLUSIONS: Head and neck
      cooling prominently reduced tympanic temperature and thus might also induce
      intracerebral hypothermia; however, it did not significantly lower body core
      temperature. Profound skin temperature decrease induced sympathetically mediated
      peripheral vasoconstriction and prominent BP increases that are not offset by
      simultaneous parasympathetic heart rate slowing. Prominent peripheral
      vasoconstriction and BP increase must be considered as possibly harmful during
      head and neck cooling.

PMID- 22627987
TI  - Letter by Sposato and Saposnik regarding article, "Socioeconomic status and
      stroke: an updated review".

PMID- 22627988
TI  - Low dietary vitamin D predicts 34-year incident stroke: the Honolulu Heart
      Program.
AB  - BACKGROUND AND PURPOSE: Vitamin D deficiency has been reported to contribute to
      the risk of cardiovascular disease, especially stroke. We examined the
      relationship between dietary vitamin D intake and 34-year incident stroke.
      METHODS: The Honolulu Heart Program is a prospective population-based cohort
      study of 8006 Japanese-American men in Hawaii who were 45 to 68 years old at the
      baseline examination in 1965 to 1968. Dietary vitamin D intake was calculated
      using the Nutritionist IV Version 3 software from a 24-hour dietary recall.
      Subjects with prevalent stroke were excluded, leaving 7385 men followed through
      1999 for incident stroke. Subjects were divided into quartiles of dietary vitamin
      D for analyses. RESULTS: During 34 years of follow-up, 960 subjects developed
      stroke. Age-adjusted rates of incident stroke were significantly higher in the
      lowest dietary vitamin D quartile compared with the highest (all stroke: 6.38
      versus 5.14 per 1000 person-years follow-up, P=0.030; thromboembolic stroke: 4.36
      versus 3.30, P=0.033). Using Cox regression, adjusting for age, total
      kilocalories, body mass index, hypertension, diabetes mellitus, pack-years
      smoking, physical activity index, serum cholesterol, and alcohol intake, those in
      the lowest quartile had a significantly increased risk of incident stroke (all
      stroke hazard ratio, 1.22; 95% CI, 1.01-1.47; P=0.038; thromboembolic stroke
      hazard ratio, 1.27; 95% CI, 1.01-1.59; P=0.044) with the highest as the
      reference. We found no significant associations between dietary vitamin D and
      hemorrhagic stroke. CONCLUSIONS: Low dietary vitamin D intake was an independent
      risk factor for 34-year incidence of all stroke and thromboembolic stroke in
      Japanese-American men. Additional research is needed on vitamin D supplementation
      to prevent stroke.

PMID- 22627989
TI  - Prediction of cardioembolic, arterial, and lacunar causes of cryptogenic stroke
      by gene expression and infarct location.
AB  - BACKGROUND AND PURPOSE: The cause of ischemic stroke remains unclear, or
      cryptogenic, in as many as 35% of patients with stroke. Not knowing the cause of
      stroke restricts optimal implementation of prevention therapy and limits stroke
      research. We demonstrate how gene expression profiles in blood can be used in
      conjunction with a measure of infarct location on neuroimaging to predict a
      probable cause in cryptogenic stroke. METHODS: The cause of cryptogenic stroke
      was predicted using previously described profiles of differentially expressed
      genes characteristic of patients with cardioembolic, arterial, and lacunar
      stroke. RNA was isolated from peripheral blood of 131 cryptogenic strokes and
      compared with profiles derived from 149 strokes of known cause. Each sample was
      run on Affymetrix U133 Plus 2.0 microarrays. Cause of cryptogenic stroke was
      predicted using gene expression in blood and infarct location. RESULTS:
      Cryptogenic strokes were predicted to be 58% cardioembolic, 18% arterial, 12%
      lacunar, and 12% unclear etiology. Cryptogenic stroke of predicted cardioembolic
      etiology had more prior myocardial infarction and higher CHA(2)DS(2)-VASc scores
      compared with stroke of predicted arterial etiology. Predicted lacunar strokes
      had higher systolic and diastolic blood pressures and lower National Institutes
      of Health Stroke Scale compared with predicted arterial and cardioembolic
      strokes. Cryptogenic strokes of unclear predicted etiology were less likely to
      have a prior transient ischemic attack or ischemic stroke. CONCLUSIONS: Gene
      expression in conjunction with a measure of infarct location can predict a
      probable cause in cryptogenic strokes. Predicted groups require further
      evaluation to determine whether relevant clinical, imaging, or therapeutic
      differences exist for each group.

PMID- 22627990
TI  - Inclusion of stroke in cardiovascular risk prediction instruments: a statement
      for healthcare professionals from the American Heart Association/American Stroke
      Association.
AB  - BACKGROUND AND PURPOSE: Current US guideline statements regarding primary and
      secondary cardiovascular risk prediction and prevention use absolute risk
      estimates to identify patients who are at high risk for vascular disease events
      and who may benefit from specific preventive interventions. These guidelines do
      not explicitly include patients with stroke, however. This statement provides an
      overview of evidence and arguments supporting (1) the inclusion of patients with
      stroke, and atherosclerotic stroke in particular, among those considered to be at
      high absolute risk of cardiovascular disease and (2) the inclusion of stroke as
      part of the outcome cluster in risk prediction instruments for vascular disease.
      METHODS AND RESULTS: Writing group members were nominated by the committee co
      chairs on the basis of their previous work in relevant topic areas and were
      approved by the American Heart Association (AHA) Stroke Council's Scientific
      Statements Oversight Committee and the AHA Manuscript Oversight Committee. The
      writers used systematic literature reviews (covering the period from January 1980
      to March 2010), reference to previously published guidelines, personal files, and
      expert opinion to summarize existing evidence, indicate gaps in current
      knowledge, and, when appropriate, formulate recommendations using standard AHA
      criteria. All members of the writing group had the opportunity to comment on the
      recommendations and approved the final version of this document. The guideline
      underwent extensive AHA internal peer review, Stroke Council leadership review,
      and Scientific Statements Oversight Committee review before consideration and
      approval by the AHA Science Advisory and Coordinating Committee. There are
      several reasons to consider stroke patients, and particularly patients with
      atherosclerotic stroke, among the groups of patients at high absolute risk of
      coronary and cardiovascular disease. First, evidence suggests that patients with
      ischemic stroke are at high absolute risk of fatal or nonfatal myocardial
      infarction or sudden death, approximating the >=20% absolute risk over 10 years
      that has been used in some guidelines to define coronary risk equivalents.
      Second, inclusion of atherosclerotic stroke would be consistent with the reasons
      for inclusion of diabetes mellitus, peripheral vascular disease, chronic kidney
      disease, and other atherosclerotic disorders despite an absence of uniformity of
      evidence of elevated risks across all populations or patients. Third, the large
      vessel atherosclerotic subtype of ischemic stroke shares pathophysiological
      mechanisms with these other disorders. Inclusion of stroke as a high-risk
      condition could result in an expansion of ~10% in the number of patients
      considered to be at high risk. However, because of the heterogeneity of stroke,
      it is uncertain whether other stroke subtypes, including hemorrhagic and
      nonatherosclerotic ischemic stroke subtypes, should be considered to be at the
      same high levels of risk, and further research is needed. Inclusion of stroke
      with myocardial infarction and sudden death among the outcome cluster of
      cardiovascular events in risk prediction instruments, moreover, is appropriate
      because of the impact of stroke on morbidity and mortality, the similarity of
      many approaches to prevention of stroke and these other forms of vascular
      disease, and the importance of stroke relative to coronary disease in some
      subpopulations. Non-US guidelines often include stroke patients among others at
      high cardiovascular risk and include stroke as a relevant outcome along with
      cardiac end points. CONCLUSIONS: Patients with atherosclerotic stroke should be
      included among those deemed to be at high risk (>=20% over 10 years) of further
      atherosclerotic coronary events. Inclusion of nonatherosclerotic stroke subtypes
      remains less certain. For the purposes of primary prevention, ischemic stroke
      should be included among cardiovascular disease outcomes in absolute risk
      assessment algorithms. The inclusion of atherosclerotic ischemic stroke as a high
      risk condition and the inclusion of ischemic stroke more broadly as an outcome
      will likely have important implications for prevention of cardiovascular disease,
      because the number of patients considered to be at high risk would grow
      substantially.

PMID- 22627991
TI  - Relation between change in blood pressure in acute stroke and risk of early
      adverse events and poor outcome.
AB  - BACKGROUND AND PURPOSE: The Scandinavian Candesartan Acute Stroke Trial (SCAST)
      found no benefits of candesartan in acute stroke. In the present analysis we aim
      to investigate the effect of change in blood pressure during the first 2 days of
      stroke on the risk of early adverse events and poor outcome. METHODS: SCAST was a
      multicenter, randomized controlled, double-blind trial of candesartan in acute
      stroke. The trial recruited 2029 patients presenting within 30 hours of acute
      stroke and with systolic blood pressure (SBP) >=140 mm Hg. Treatment was given
      for 7 days. Change in blood pressure was defined as the difference in SBP between
      baseline and Day 2 and was used to divide patients into groups with increase/no
      change, a small decrease, moderate decrease, or large decrease in SBP. The
      primary effect parameter was early adverse events (recurrent stroke, stroke
      progression, and symptomatic hypotension) during the first 7 days, analyzed using
      logistic regression, with the group with a small decrease in SBP as the reference
      group. Secondary effect parameters were neurological status at 7 days and
      functional outcome at 6 months. RESULTS: Patients with a large decrease or
      increase/no change in SBP had a significantly increased risk of early adverse
      events relative to patients with a small decrease (OR, 2.08; 95% CI, 1.19-3.65
      and OR, 1.96; 95% CI, 1.13-3.38, respectively). Patients with an increase/no
      change in SBP had a significantly increased risk of poor neurological outcome as
      compared with the other groups (P=0.001). No differences were observed in
      functional outcome at 6 months. CONCLUSIONS: Our findings support the suggestion
      from SCAST that blood pressure reduction may be harmful and that routine blood
      pressure-lowering treatment should probably be avoided in the acute phase.
      CLINICAL TRIAL INFORMATION:  CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov.
      Unique identifier: NCT00120003.

PMID- 22627992
TI  - The neural basis of anosognosia for spatial neglect after stroke.
AB  - BACKGROUND AND PURPOSE: The present study investigated the lesion anatomy of
      anosognosia for visuospatial neglect resulting from right hemispheric stroke.
      METHODS: In 63 patients, self-ratings of performance in paper-and-pencil tests
      were contrasted with external performance ratings. Lesion analysis was conducted
      on patient subgroups with different degrees of anosognosia but comparable
      visuospatial impairment. RESULTS: Independent of the severity of visuospatial
      neglect per se, damage to the right angular and superior temporal gyrus was
      associated with higher levels of anosognosia. CONCLUSIONS: Using a novel
      assessment of anosognosia for spatial neglect, the present study relates stroke
      induced self-awareness deficits to inferior parietal and superior temporal brain
      damage.

PMID- 22627993
TI  - Graphene oxide-Fe3O4 magnetic nanocomposites with peroxidase-like activity for
      colorimetric detection of glucose.
AB  - In this report, graphene oxide-Fe(3)O(4) magnetic nanocomposites were
      demonstrated to possess intrinsic peroxidase-like activity and enhanced affinity
      toward H(2)O(2). The nanocomposites retain their magnetic properties and can be
      effectively separated by a magnet. Significantly, they were proved to be novel
      peroxidase mimetics which could quickly catalyze oxidation of the peroxidase
      substrate 3,3,5,5-tetramethylbenzidine (TMB) in the presence of H(2)O(2),
      producing a blue-colored solution. Kinetic analysis indicates that the catalytic
      behavior is in accord with typical Michaelis-Menten kinetics and follows a ping
      pong mechanism. On the basis of the high activity, the reaction provides a
      simple, sensitive and selective method for colorimetric detection of glucose in
      diabetic urine.

PMID- 22627995
TI  - Metamaterial electromagnetic wave absorbers.
AB  - The advent of negative index materials has spawned extensive research into
      metamaterials over the past decade. Metamaterials are attractive not only for
      their exotic electromagnetic properties, but also their promise for applications.
      A particular branch-the metamaterial perfect absorber (MPA)-has garnered interest
      due to the fact that it can achieve unity absorptivity of electromagnetic waves.
      Since its first experimental demonstration in 2008, the MPA has progressed
      significantly with designs shown across the electromagnetic spectrum, from
      microwave to optical. In this Progress Report we give an overview of the field
      and discuss a selection of examples and related applications. The ability of the
      MPA to exhibit extreme performance flexibility will be discussed and the theory
      underlying their operation and limitations will be established. Insight is given
      into what we can expect from this rapidly expanding field and future challenges
      will be addressed.

PMID- 22627994
TI  - Comparison of prognosis in patients with endometrioid endometrial cancer staged
      IB in FIGO 1988 and 2009 classifications.
AB  - PURPOSE: Since 2009 the new FIGO Staging System of endometrial cancer, which
      changed the previous FIGO 1988 Staging System, has been in use. The aim of the
      study was to compare prognosis in patients with endometrioid endometrial cancer
      at stage IB of the 2009 FIGO Staging System and of the 1988 FIGO Staging System.
      METHODS: We analyzed 173 patients: 108 patients (group A) at stage IB in FIGO
      1988 Staging System, and 68 patients (group B) at stage IB in FIGO 2009 Staging
      System from 262 consecutive endometrioid endometrial cancer patients. The disease
      free survival (DFS) and overall survival (OS) were compared between these groups.
      RESULTS: The DFS rate was 96.3 % in group A and it was 87.7 % in group B (p =
      0.029). Relapses were observed in 12 patients (6.4 %) from 6 to 57 months (mean
      28.1; SD = 14.6) after initial surgery, and occurred in four patients from group
      A (3.7 %) and eight patients from group B (12.3 %) (p = 0.032). The OS rate was
      94.4 % in group A and it was 83.1 % in group B (p = 0.018). During follow-up, 17
      patients (9.8 %) died: six patients from group A (5.6 %), and 11 patients from
      group B (16.9 %). CONCLUSIONS: Stage IB in FIGO 2009 Staging System is associated
      with worse prognosis compared to stage IB according to FIGO 1988 classification.
      There seems to be a need to use exclusively the new FIGO 2009 classification
      worldwide to avoid therapeutic mistakes, which can be caused by diverse
      nomenclature.

PMID- 22627996
TI  - Xanthorrhizol induces apoptosis through ROS-mediated MAPK activation in human
      oral squamous cell carcinoma cells and inhibits DMBA-induced oral carcinogenesis
      in hamsters.
AB  - Xanthorrhizol, a natural sesquiterpenoid compound isolated from Curcuma
      xanthorrhiza Roxb, has been known to inhibit the growth of human colon, breast,
      liver and cervical cancer cells. In this study, xanthorrhizol decreased cell
      viability, induced apoptosis and decreased the level of full-length PARP in SCC
      15 oral squamous cell carcinoma (OSCC) cells. A decrease in cell viability and
      PARP degradation was not prevented by treatment with the caspase inhibitor Z-VAD
      fmk in xanthorrhizol-treated cells. Xanthorrhizol treatment elevated
      intracellular Ca(2+) and ROS levels in SCC-15 cells. Treatment with a Ca(2+)
      chelator, EGTA/AM, did not affect xanthorrhizol- induced cytotoxicity, but cell
      viability was partly recovered by treatment with endogenous antioxidant, GSH, or
      hydroxy radical trapper, MCI-186. Furthermore, the viability of xanthorrhizol
      treated SCC-15 cells was significantly restored by treatment with SB203580 and/or
      SP600125 but not significantly by PD98059 treatment. Xanthorrhizol-induced
      activation of p38 MAPK and JNK was blocked by MCI-186. Finally, xanthorrhizol
      suppressed the number of tumors in buccal pouches and increased the survival rate
      in hamsters treated with 7,12-dimethylbenz[a]anthracene. In conclusion,
      xanthorrhizol may induce caspase-independent apoptosis through ROS-mediated p38
      MAPK and JNK activation in SCC-15 OSCC cells and prevent chemical-induced oral
      carcinogenesis. Therefore, xanthorrhizol seems to be a promising chemopreventive
      agent.

PMID- 22627998
TI  - Hydrogen evolution across nano-Schottky junctions at carbon supported MoS2
      catalysts in biphasic liquid systems.
AB  - The activities of a series of MoS(2)-based hydrogen evolution catalysts were
      studied by biphasic reactions monitored by UV/Vis spectroscopy. Carbon supported
      MoS(2) catalysts performed best due to an abundance of catalytic edge sites and
      strong electronic coupling of catalyst to support.

PMID- 22627999
TI  - Treatment of depression in older adults.
AB  - Depression is the most frequent mental disorder in older people, often causing
      emotional distress and reduced quality of life. Despite its clinical
      significance, depression remains underdiagnosed and inadequately treated in older
      patients. Regarding prognosis, data suggest that almost 70% of patients, treated
      long enough and with appropriate doses, recover from an index episode of
      depression. Antidepressants are efficient for treating depressed outpatients with
      several comorbid physical diseases as well as hospitalized patients, with
      selective serotonin reuptake inhibitors being the antidepressants of choice for
      older patients. Available data can guide pharmacological treatment in both the
      acute and maintenance stages, but further research is required to guide clinical
      strategies when remission is not achieved. Approaches for the management of
      resistance to treatment are summarized, including optimization strategies, drug
      changes, algorithms, and combined and augmentation pharmacological treatments.
      Finally, additional therapeutic choices such as electroconvulsive therapy,
      transcranial magnetic stimulation, and integrated psychotherapy are presented.

PMID- 22628000
TI  - Antipsychotic agents in the treatment of anorexia nervosa:
      neuropsychopharmacologic rationale and evidence from controlled trials.
AB  - The search for an effective psychopharmacologic strategy in the treatment of
      anorexia nervosa (AN) has been elusive for decades and has run the gamut from
      reserpine to typical antipsychotics, to lithium, to tetrahydrocannabinol, to
      growth hormone, to anticonvulsants, to antidepressants, to atypical
      antipsychotics. Only recently has there arisen a potential "diamond in the rough"
      in the form of the atypical antipsychotic agent, olanzapine, which, in four
      randomized clinical trials, has shown superiority to placebo (two studies),
      chlorpromazine (one study), and aripiprazole (one study) in terms of weight gain
      and/or reduction in obsessional symptoms. The pharmacologic profile of olanzapine
      and other antipsychotic medications is discussed in light of the known
      pathophysiology of AN involving serotonin and dopamine systems, as well as brain
      derived neurotrophic factor.

PMID- 22628001
TI  - Boosting (19) F MRI-SNR efficient detection of paramagnetic contrast agents using
      ultrafast sequences.
AB  - (19) F MRI offers high specificity but usually low sensitivity. Here,
      paramagnetic relaxation enhancement is assessed as a method to improve SNR
      efficiency in (19) F MRI. Compounds with short relaxation times are used that
      combine fluorine and a paramagnetic ion within the same molecule. Different
      molecular designs provide T1 values in the range of 1.4-15 ms and T2*/T1 ratios
      from 0.3 to 1. Gradient echo, as well as ultrafast radial MR sequences, is
      optimized to achieve highest SNR efficiency. Compared to nonparamagnetic
      compounds, ultrafast sequences can yield a gain of up to a factor 27 in
      sensitivity, whereas the gain with gradient echo is only factor 11. Comparison
      among the paramagnetic compounds shows that T2*/T1 close to unity is a
      prerequisite for highest SNR efficiency gain and that best results are obtained
      for compounds with T1 in the range of 1-5 ms.

PMID- 22628002
TI  - Comparative effectiveness research in cancer screening programmes.

PMID- 22628003
TI  - Comparisons of established risk prediction models for cardiovascular disease:
      systematic review.
AB  - OBJECTIVE: To evaluate the evidence on comparisons of established cardiovascular
      risk prediction models and to collect comparative information on their relative
      prognostic performance. DESIGN: Systematic review of comparative predictive model
      studies. DATA SOURCES: Medline and screening of citations and references. STUDY
      SELECTION: Studies examining the relative prognostic performance of at least two
      major risk models for cardiovascular disease in general populations. DATA
      EXTRACTION: Information on study design, assessed risk models, and outcomes. We
      examined the relative performance of the models (discrimination, calibration, and
      reclassification) and the potential for outcome selection and optimism biases
      favouring newly introduced models and models developed by the authors. RESULTS:
      20 articles including 56 pairwise comparisons of eight models (two variants of
      the Framingham risk score, the assessing cardiovascular risk to Scottish
      Intercollegiate Guidelines Network to assign preventative treatment (ASSIGN)
      score, systematic coronary risk evaluation (SCORE) score, Prospective
      Cardiovascular Munster (PROCAM) score, QRESEARCH cardiovascular risk (QRISK1 and
      QRISK2) algorithms, Reynolds risk score) were eligible. Only 10 of 56 comparisons
      exceeded a 5% relative difference based on the area under the receiver operating
      characteristic curve. Use of other discrimination, calibration, and
      reclassification statistics was less consistent. In 32 comparisons, an outcome
      was used that had been used in the original development of only one of the
      compared models, and in 25 of these comparisons (78%) the outcome-congruent model
      had a better area under the receiver operating characteristic curve. Moreover,
      authors always reported better area under the receiver operating characteristic
      curves for models that they themselves developed (in five articles on newly
      introduced models and in three articles on subsequent evaluations). CONCLUSIONS:
      Several risk prediction models for cardiovascular disease are available and their
      head to head comparisons would benefit from standardised reporting and formal,
      consistent statistical comparisons. Outcome selection and optimism biases
      apparently affect this literature.

PMID- 22628004
TI  - Southall: the GMC responds.

PMID- 22628005
TI  - Time to end the distinction between mental and neurological illnesses.

PMID- 22628006
TI  - Blood stained nappy.

PMID- 22628007
TI  - Experts attack government plans to cuts benefits for addicts who refuse
      treatment.

PMID- 22628008
TI  - Enhanced dispersibility and cellular transmembrane capability of single-wall
      carbon nanotubes by polycyclic organic compounds as chaperon.
AB  - The common aggregation of single-wall carbon nanotube (SWCNT) in solution is the
      critical obstacle to elucidate their unique physico-chemical characteristics and
      biological properties. Therefore, it is very important to overcome this barrier
      through manipulation of the weak interaction of small molecules with nanotube
      surface limited interface. A highly dispersed SWCNT system was achieved by
      binding with polycyclic organic compounds (POCs) including rhodamine 123,
      ethidium bromide, fluorescein isothiocyanate and 1-pyrene butyric acid as
      chaperons, in cooperation with sodium dodecyl sulfate. POCs were believed to
      penetrate through the interstices of aggregated SWCNTs and bind with individual
      SWCNTs to form highly dispersed and stable SWCNT-POC-surfactant conjugates in
      both water and phosphate buffer-serum solution, confirmed by gel electrophoresis,
      transmission electron microscopy and atomic force microscopy. The possible
      binding interaction includes pi-pi stacking with side-wall, electrostatic
      interactions with defect sites and coating surfactants. Compared to pristine
      SWCNTs, individual SWCNT-POC conjugates had improved transmembrane passage
      ability through both endocytosis and diffusion pathways, validated by laser
      scanning confocal microscopy and micro-Raman mapping techniques. For the
      applications of SWCNTs in drug delivery, in vitro imaging and other research
      fields, this novel strategy could provide highly dispersed SWCNTs with better
      efficiency of drug loading and stability.

PMID- 22628009
TI  - Encapsulating zinc(II) within a hydrophobic cavity.
AB  - A new macrobicyclic ligand has been prepared, and it is shown to bind Zn(2+) on
      the inside. The ligand consists of a triamido(amine) motif to coordinate the
      metal ion and a narrow, hydrophobic channel above the metal binding site.

PMID- 22628010
TI  - Cancer morbidity of professional emergency responders in Korea.
AB  - BACKGROUND: Many professional emergency responders (ERs) who belong to the Korean
      National Emergency Management Agency (NEMA) have been cross-trained and serve
      multiple roles. As such, firefighters and other ERs in Korea are exposed to
      similar occupational hazards. This study was conducted to estimate cancer
      morbidity in male ERs and compare that with Korean men. METHODS: The cohort was
      comprised of 33,416 male ERs working between 1980 and 2007, who were alive on
      December 31, 1995. Work histories were merged with the Korea National Central
      Cancer Registry (KNCCR) to assess cancer morbidity between 1996 and 2007.
      Standardized incidence ratios (SIRs) with reference to Korean men were analyzed.
      RESULTS: SIRs with reference to national cancer rates were not significantly
      decreased for overall cancer (SIR = 0.97, 95% CI = 0.90-1.08) in all ERs.
      However, colorectal (SIR = 1.35, 95% CI = 1.07-1.67), kidney (SIR = 1.59, 95% CI
      = 1.00-2.41), and bladder (SIR = 1.77, 95% CI = 1.08-2.73) cancer, and non
      Hodgkin's lymphoma (SIR = 1.81, 95% CI = 1.12-2.76) morbidities were
      significantly increased among all ERs. In firefighters, significantly increased
      cancer types were as same as those of all ERs. In non-firefighter ERs, colorectal
      (SIR = 2.51, 95% CI = 1.20-4.61) and bone and articular cartilage cancers (SIR =
      9.53, 95% CI = 1.07-34.41) were significantly higher than those of Korean men.
      CONCLUSIONS: Korean firefighters showed excess morbidity in several cancer types,
      including colorectal and urologic cancers, and non-Hodgkin's lymphoma,
      demonstrating similar trends to previous studies for firefighters conducted in
      other countries. Increased incidence in these cancer types suggests occupational
      exposure to carcinogens and shift work.

PMID- 22628011
TI  - FoxO function PAR excellence...

PMID- 22628013
TI  - Lethal factor VII deficiency due to novel mutations in the F7 promoter:
      functional analysis reveals disruption of HNF4 binding site.
AB  - Hereditary factor VII (FVII) deficiency is a rare autosomal recessive disorder.
      Deleterious mutations that prevent the synthesis of any amount of functional FVII
      have been associated with life-threatening haemorrhage in neonates. Here we
      report two infants, of Maghrebian origin, who suffered a fatal spontaneous
      cerebral haemorrhage. Investigation of the molecular basis for their severe FVII
      deficiency revealed novel mutations in a homozygous state within the  F7  gene
      promoter: a single nucleotide substitution (c.-65G>C) and a 2bp deletion (c.-60_
      59delTT). To determine whether these promoter variants were responsible for the
      FVII deficiency, computer-assisted sequence analyses were performed. The data
      predicted a disrupted binding of both HNF4 and COUP-TF transcription factors with
      each variant. Concordantly, experimental results revealed an altered HNF4-induced
      transactivation in the promoter mutated variants. The execution of functional
      tests is critical to ensuring a complete understanding of the effect of any
      promoter mutant on FVII deficiency. Only then can an accurate molecular diagnosis
      be made and further genetic counselling and prenatal diagnosis be offered.

PMID- 22628012
TI  - Birth of neural progenitors during the embryonic period of sexual differentiation
      in the Japanese quail brain.
AB  - Several brain areas in the diencephalon are involved in the activation and
      expression of sexual behavior, including in quail the medial preoptic nucleus
      (POM). However, the ontogeny of these diencephalic brain nuclei has not to this
      date been examined in detail. We investigated the ontogeny of POM and other
      steroid-sensitive brain regions by injecting quail eggs with 5-bromo-2
      deoxyuridine (BrdU) at various stages between embryonic day (E)3 and E16 and
      killing animals at postnatal (PN) days 3 or 56. In the POM, large numbers of BrdU
      positive cells were observed in subjects injected from E3-E10, the numbers of
      these cells was intermediate in birds injected on E12, and most cells were
      postmitotic in both sexes on E14-E16. Injections on E3-E4 labeled large numbers
      of Hu-positive cells in POM. In contrast, injections performed at a later stage
      labeled cells that do not express aromatase nor neuronal markers such as Hu or
      NeuN in the POM and other steroid-sensitive nuclei and thus do not have a
      neuronal phenotype in these locations, contrary to what is observed in the
      telencephalon and cerebellum. No evidence could also be collected to demonstrate
      that these cells have a glial nature. Converging data, including the facts that
      these cells divide in the brain mantle and express proliferating cell nuclear
      antigen (PCNA), a cell cycling marker, indicate that cells labeled by BrdU during
      the second half of embryonic life are slow-cycling progenitors born and residing
      in the brain mantle. Future research should now identify their functional
      significance.

PMID- 22628014
TI  - A new water-soluble pillar[5]arene: synthesis and application in the preparation
      of gold nanoparticles.
AB  - A new water-soluble pillar[5]arene containing ten imidazolium groups was
      prepared. It can be used as a stabilizer to fabricate gold nanoparticles smaller
      than 6 nm in water.

PMID- 22628015
TI  - Neuronal properties, in vivo effects, and pathology of a Huntington's disease
      patient-derived induced pluripotent stem cells.
AB  - Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients
      can be used to model different human diseases. They may also serve as sources of
      transplantable cells that can be used in novel cell therapies. Here, we analyzed
      neuronal properties of an iPSC line derived from a patient with a juvenile form
      of Huntington's disease (HD) carrying 72 CAG repeats (HD-iPSC). Although its
      initial neural inducing activity was lower than that of human embryonic stem
      cells, we found that HD-iPSC can give rise to GABAergic striatal neurons, the
      neuronal cell type that is most susceptible to degeneration in HD. We then
      transplanted HD-iPSC-derived neural precursors into a rat model of HD with a
      unilateral excitotoxic striatal lesion and observed a significant behavioral
      recovery in the grafted rats. Interestingly, during our in vitro culture and when
      the grafts were examined at 12 weeks after transplantation, no aggregate
      formation was detected. However, when the culture was treated with a proteasome
      inhibitor (MG132) or when the cells engrafted into neonatal brains were analyzed
      at 33 weeks, there were clear signs of HD pathology. Taken together, these
      results indicate that, although HD-iPSC carrying 72 CAG repeats can form
      GABAergic neurons and give rise to functional effects in vivo, without showing an
      overt HD phenotype, it is highly susceptible to proteasome inhibition and
      develops HD pathology at later stages of transplantation. These unique features
      of HD-iPSC will serve as useful tools to study HD pathology and develop novel
      therapeutics.

PMID- 22628016
TI  - Risk of bleeding associated with use of systemic thromboembolic prophylaxis
      during laparoscopic cholecystectomy.
AB  - BACKGROUND: The extent to which systemic perioperative thromboembolic prophylaxis
      affects peroperative and postoperative bleeding during cholecystectomy is not
      known. This article reports on risk of bleeding in a national cohort of
      cholecystectomies. METHODS: All cholecystectomies registered in the Swedish
      Register of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography
      (GallRiks) between 2005 and 2010 were reviewed. Peroperative bleeding was defined
      as bleeding that could not be controlled by standard surgical techniques,
      necessitated conversion to an open procedure or required peroperative blood
      transfusion. Postoperative bleeding was defined as bleeding that necessitated
      reoperation, transfusion or a prolonged hospital stay. Risk estimates were
      performed using univariable and multiple logistic regression, and reported as
      odds ratios (ORs). RESULTS: A total of 51 621 procedures were registered in
      GallRiks. Some 48 010 patients were included in the analyses, of whom 21 259
      (44.3 per cent) received thromboembolic prophylaxis. Peroperative bleeding
      complications occurred in 400 (1.9 per cent) and postoperative bleeding in 296
      (1.4 per cent) given thromboembolic prophylaxis, compared with 189 (0.7 per cent)
      and 195 (0.7 per cent) respectively without thromboprophylaxis. After adjusting
      for age, sex, indication for surgery, American Society of Anesthesiologists
      grade, mode of admission, operative approach, duration of surgery and hospital
      volume, the OR for peroperative or postoperative bleeding complications in the
      group receiving prophylaxis was 1.35 (95 per cent confidence interval 1.17 to
      1.55). However, in a subgroup analysis the risk was increased in laparoscopic
      surgery only. At 30-day follow-up, a total of 74 patients (0.2 per cent) had
      developed postoperative thromboembolism, 43 (0.2 per cent) of those who received
      thromboembolic prophylaxis compared with 31 (0.1 per cent) of those who did not.
      CONCLUSION: Thromboprophylaxis in patients undergoing laparoscopic
      cholecystectomy increased the risk of bleeding, but the occurrence of
      thromboembolic events was not significantly reduced. Identification of high- and
      low-risk patients is needed to guide clinical decisions regarding medical
      thromboprophylaxis.

PMID- 22628017
TI  - Direct effects of Vaccinium myrtillus L. fruit extracts on rat heart
      mitochondrial functions.
AB  - In this study, the direct influence of bilberry (Vaccinium myrtillus) fruit
      extracts (aqueous and ethanolic) rich in anthocyanins on the oxidative
      phosphorylation of isolated rat heart mitochondria was investigated in vitro.
      Higher concentrations of bilberry extracts concentration-dependently inhibited
      mitochondrial state 3 respiration (by 23%-61%) with pyruvate plus malate, mildly
      (by 1.2- to 1.3-fold) uncoupled the oxidative phosphorylation, and increased (by
      30%-87%) the state 4 respiration rate in the presence of exogenous cytochrome c.
      Succinate oxidation was less affected. Pure anthocyanins, the main components of
      used extracts, malvidin-3-glucoside, malvidin-3-galactoside, and cyanidin-3
      galactoside, had no effect on oxidation of pyruvate plus malate. A statistically
      significant decrease in H2 O2 production by mitochondria was found in the
      presence of bilberry fruit extracts. Our findings show that bilberry fruit
      anthocyanin-rich extracts possess direct effects on rat heart mitochondrial
      function in vitro. These findings give the first insights into the mechanism(s)
      of their action on cellular energy metabolism.

PMID- 22628021
TI  - Transparent nanoscale floating gate memory using self-assembled bismuth
      nanocrystals in Bi(2) Mg(2/3) Nb(4/3) O(7) (BMN) pyrochlore thin films grown at
      room temperature.
AB  - Bismuth nanocrystals for a nanoscale floating gate memory device are self
      assembled in Bi(2) Mg(2/3) Nb(4/3) O(7)  (BMN) dielectric films grown at room
      temperature by radio-frequency sputtering. The TEM cross-sectional image shows
      the "real" structure grown on a Si (001) substrate. The image magnified from the
      dotted box (red color) in the the cross-sectional image clearly shows bismuth
      nanoparticles at the interface between the Al(2) O(3)  and HfO(2)  layer (right
      image). Nanoparticles approximately 3 nm in size are regularly distributed at the
      interface.

PMID- 22628022
TI  - Genetic modifications and introduction of heterologous pdc genes in Enterococcus
      faecalis for its use in production of bioethanol.
AB  - Genetically-modified Enterococcus faecalis has a potential of survival and can be
      used in ethanolic fermentations. Fermentation profiles of E. faecalis JH2-2 were
      assessed using glucose and lactose as carbon sources. Deletion of lactate
      dehydrogenase (ldh) genes increased the ethanol production from 0.25 to 0.82 g/l,
      which was further increased to 0.96 g/l by the insertion of a pyruvate
      decarboxylase (pdc) gene (from Sarcina ventriculi or Clostridium acetobutylicum)
      in place ldh1. When grown on lactose, the pdcSv and pdcCa showed 13.6 and 17.6 U
      mg(-1) of pdc specific activity, respectively. Highest activity (47 U mg(-1)) and
      ethanol concentration (2.3 g/l) were obtained with pdcCa using an expression
      plasmid. Formate and acetate were also produced in high quantities.
      Transcriptional analysis showed that aldehyde alcohol dehydrogenase gene was
      upregulated up to 16-fold. Further optimizations are required for higher ethanol
      production.

PMID- 22628024
TI  - [Epidural anesthesia-analgesia: still great effort is needed to avoid serious
      problems!].

PMID- 22628023
TI  - IL-10 -1082 SNP and IL-10 in primary CNS and vitreoretinal lymphomas.
AB  - OBJECTIVES: Most primary central nervous system lymphomas (PCNSLs) and primary
      vitreoretinal lymphomas (PVRLs) are B-cell lymphomas that produce high levels of
      interleukin (IL)-10, which is linked to rapid disease progression. The IL-10 (
      1082) G -> A polymorphism (IL-10 SNP) is associated with improved survival in
      certain non-CNS lymphoma patients. PDCD4 is a tumor suppressor gene and upstream
      regulator of IL-10. This study examined the correlation between the IL-10 SNP,
      PDCD4 mRNA expression, and IL-10 expression (at transcript and protein levels) in
      these lymphoma cells. MATERIALS AND METHODS: Single-nucleotide polymorphism (SNP)
      typing at IL-10 (-1082) was performed after microdissecting cytospun PVRL cells
      from 26 specimens. Vitreal IL-10 and IL-6 levels were measured by ELISA. PCNSL
      cells from 52 paraffin-embedded sections were microdissected and SNP typed on
      genomic DNA. RT-PCR was performed to analyze expression of IL-10 and PDCD4 mRNA.
      IL-10 (-1082) SNP typing was performed on blood samples of 96 healthy controls.
      We measured IL-10 (-1082) SNP expression in 26 PVRLs and 52 PCNSLs and examined
      its relationship with IL-10 protein and gene expression, respectively. RESULTS:
      More PVRL patients expressed one copy of the IL-10 ( -1082 ) G -> A SNP with the
      GA genotype compared to controls. The frequencies of the three genotypes (AA, AG,
      GG) significantly differed in PVRL versus controls and in PCNSL versus controls.
      In PVRLs, the vitreal IL-10/IL-6 ratio was higher in IL-10 (-1082) AG and IL-10 (
      1082) AA patients, compared to IL-10 (-1082) GG patients. IL-10 mRNA expression
      was higher in IL-10 (-1082) AG and IL-10 (-1082) AA PCNSLs, compared to IL-10 (
      1082) GG PCNSLs. No correlation was found between IL-10 and PDCD4 expression
      levels in 37 PCNSL samples. CONCLUSIONS: PVRL and PCNSL patients had similar IL
      10 (-1082) A allele frequencies, but genotype distributions differed from healthy
      controls. The findings suggest that the IL-10 (-1082) A allele is a risk factor
      for higher IL-10 levels in PVRLs and PCNSLs. Higher IL-10 levels have been
      correlated with more aggressive disease in both PVRLs and PCNSLs, making this
      finding an important and potentially clinically significant observation.

PMID- 22628025
TI  - [Muscle relaxants and neuromuscular monitoring - Introduction for a safe clinical
      application].
AB  - The use of muscle relaxants facilitates endotracheal intubation and ameliorates
      the conditions of surgery. But, their use should be controlled - otherwise there
      will be postoperative residual curarisation which can lead to patient discomfort
      up to severe medical complications. Therefore, an appropriate surveillance via
      objective neuromuscular monitoring is essential. This article gives a review of
      the basic principles of muscle relaxants, their clinical application and the
      surveillance of their effects and degradation.

PMID- 22628026
TI  - [Case Report: Recurrent postpartum haemorrhage after emergency caesarean section 
      Clipping, embolization and haemostaseological therapy].
AB  - Immediately after emergency caesarean section a 37 yr old patient suffered severe
      atonic bleeding requiring different operating procedures (Clipping of the uterine
      arteries) in combination with an uterotonic and haemostaseological medication as
      well as massive transfusion of blood components and recombinant factor VIIa.
      After a period of 17 days without any bleeding the patient presented to the
      emergency room with recurrent massive uterine bleeding. Transarterial
      embolization of the anterior bundles of the iliac arteries in combination with a
      second uterotonic and haemostaseological medication stopped the haemorrhage.
      Reasons and risk factors of a recurrent postpartum bleeding are discussed and a
      multidisciplinary algorithm for treatment is proposed.

PMID- 22628027
TI  - [Nerve damage in regional anesthesia - A complication and many possible causes].

PMID- 22628028
TI  - [Nerve injuries associated with nerve blocks: clinic and incidence].
AB  - Persistent nerve injuries in context of peripheral nerve blocks are uncommon.
      Previous surveys and prospectively designed studies have specified neurological
      dysfunctions in different ways, which may cause the variability of data about
      incidence; so it has to be reckoned with about 5% after 1 week, 1% after 1 month
      and 0,01% after 6 months. Amongst the different locations interscalene blocks
      with their associated surgical procedures seem to have the highest incidence.
      Establishing the correlation between disabilities and the performed block
      technique often constitutes difficulties, especially when other reasons like
      patient positioning techniques, tractions, ischemia and surgery related nerve
      injuries have to be considered. Dysfunctions manifest as numbness, parasthesia,
      tingling sensation and/or amyasthenia. Fortunately long-term lesions, caused by
      nerve blocks are a rarity.

PMID- 22628029
TI  - [Nerve injury due to peripheral nerve blocks: Pathophysiology and aetiology].
AB  - Permanent nerve injury as a complication of peripheral regional anaesthesia is
      fortunately rare with an estimated incidence of 0,03%. However, transient
      neurological symptoms are more frequent with an occurrence of 3-8%. The
      pathophysiology and etiology of nerve injury depends on a number of different
      factors. The needle-nerve trauma, cytotoxicity of local anaesthetics, patient
      factors (i.e. morbidity) and factors which are related to surgical interventions
      should be considered. Regarding pathophysiology, trauma-related inflammation
      should be acknowledged as an important interference during nerve recovery. Needle
      nerve contacts, nerve perforation and local cytotoxicity of local anaesthetics
      should be reduced to a minimum by application of nerve stimulation, ultrasound
      and an adequate dosage of local anaesthetics with less locotoxicity.

PMID- 22628030
TI  - [Neurologic complications after epidural analgesia].
AB  - Epidural analgesia is regarded as gold standard after major abdominal or thoracic
      surgery in combination with general anaesthesia. Apart from well documented
      positive effects of epidural analgesia on the postoperative period, evidence for
      the incidence of neurologic complications is less clear. Complications include
      direct spinal cord damage during epidural puncture, epidural hematoma, abscesses
      or meningitis. The review article gives an overview about current data on
      neurologic complications related to epidural analgesia and shows feasibility of
      prevention and early detection. Furthermore a therapeutic approach in case of a
      neurologic incident will be demonstrated.

PMID- 22628031
TI  - [Rare medical incidents: Actual consensus statement for the removal of neuraxial
      catheter fragments].
AB  - The rupture of a catheter near the spine is rare. There are no evidence-based
      guidelines for diagnosis and therapy. Opinions derived from German
      anesthesiologists, neurosurgeons, orthopaedics and trauma surgeons are: Infants
      should have immediate surgery. In an asymptomatic adult, the catheter fragment
      does not require removal surgery. Antibiotic prophylaxis is not necessary. If
      symptomatic, the catheter fragment should be localized by a thin slice computed
      tomography or fluoroscopy. Otherwise surgical exploration is indicated. Direct
      surgery is recommended for cases with neurological symptoms, infections, loss of
      spinal fluid, pain and local discomfort. Relative indications for surgery are
      severe pain, tissue infection and intrathecal localization of the fragment.
      Surgery should be performed in prone position and under general anesthesia.
      Starting at the entry wound, the surgical access should be microsurgical and
      preferably by a neurosurgeon. If the entry is not detectable, a midline incision
      is suggested.

PMID- 22628032
TI  - [Shortage of physicians in anaesthesiology and intensive care medicine - Causes,
      consequences and solutions].
AB  - 74% of all hospitals had vacant positions in 2011, also departments of
      anaesthesiology and intensive care medicine. More than 50% of these departments
      work with locums. There are couple of reasons for the shortage of physicians. The
      consequences in anaesthesiology and intensive care medicine can result in
      qualitative and financial loss. To solve the shortage of physicians one has to
      solve the reasons. Main reasons are increasing feminization of medical profession
      and part-time-work, work-life-balance and a poor specialised education.

PMID- 22628033
TI  - Adding a radial dimension to the assessment of esophagogastric junction
      relaxation: validation studies of the 3D-eSleeve.
AB  - High-resolution manometry (HRM) with esophageal pressure topography (EPT) allowed
      for the establishment of an objective quantitative measurement of esophagogastric
      junction (EGJ) relaxation, the integrated relaxation pressure (IRP). This study
      assessed whether or not a novel 3D-HRM assembly could improve on this
      measurement. Twenty-five normal subjects were studied with both a standard HRM
      assembly and a novel hybrid assembly (3D-HRM), including a 9.0 cm 3D-HRM segment
      composed of 96 radially dispersed independent pressure sensors. The standard IRP
      was computed using each assembly and compared with a novel paradigm, the 3D-IRP,
      an analysis premised on finding the axial maximum and radial minimum pressure at
      each sensor ring along the sleeve segment. Fourteen additional subjects underwent
      barium swallows with 3D-HRM and concurrent videofluoroscopy to compare the
      electronic sleeve (eSleeve) paradigm (circumferential average) to the 3D eSleeve
      paradigm (radial minimum) as a predictor of transphincteric flow. The 3D-IRP was
      significantly less than all other calculations of IRP with the upper limit of
      normal being 12 mmHg vs. 17 mmHg for the standard IRP. The sensitivity (0.78) and
      the specificity (0.88) of the 3D-eSleeve were also better than the standard
      eSleeve (0.55 and 0.85, respectively) for predicting flow permissive time
      verified fluoroscopically. The 3D-IRP and 3D-eSleeve calculated using the radial
      pressure minimum lowered the normative range of EGJ relaxation (upper limit of
      normal 12 mmHg) and yielded intraluminal pressure gradients that better
      correlated with bolus flow than did analysis paradigms based on circumferentially
      averaged pressure.

PMID- 22628035
TI  - Firing patterns and functional roles of different classes of spinal afferents in
      rectal nerves during colonic migrating motor complexes in mouse colon.
AB  - The functional role of the different classes of visceral afferents that innervate
      the large intestine is poorly understood. Recent evidence suggests that low
      threshold, wide-dynamic-range rectal afferents play an important role in the
      detection and transmission of visceral pain induced by noxious colorectal
      distension in mice. However, it is not clear which classes of spinal afferents
      are activated during naturally occurring colonic motor patterns or during intense
      contractions of the gut smooth muscle. We developed an in vitro colorectum
      preparation to test how the major classes of rectal afferents are activated
      during spontaneous colonic migrating motor complex (CMMC) or pharmacologically
      induced contraction. During CMMCs, circular muscle contractions increased firing
      in low-threshold, wide-dynamic-range muscular afferents and muscular-mucosal
      afferents, which generated a mean firing rate of 1.53 +/- 0.23 Hz (n = 8) under
      isotonic conditions and 2.52 +/- 0.36 Hz (n = 17) under isometric conditions.
      These low-threshold rectal afferents were reliably activated by low levels of
      circumferential stretch induced by increases in length (1-2 mm) or load (1-3 g).
      In a small proportion of cases (5 of 34 units), some low-threshold muscular and
      muscular-mucosal afferents decreased their firing rate during the peak of the
      CMMC contractions. High-threshold afferents were never activated during
      spontaneous CMMC contractions or tonic contractions induced by bethanechol (100
      MUM). High-threshold rectal afferents were only activated by intense levels of
      circumferential stretch (10-20 g). These results show that, in the rectal nerves
      of mice, low-threshold, wide-dynamic-range muscular and muscular-mucosal
      afferents are excited during contraction of the circular muscle that occurs
      during spontaneous CMMCs. No activation of high-threshold rectal afferents was
      detected during CMMCs or intense contractile activity in naive mouse colorectum.

PMID- 22628034
TI  - Delineation of biochemical, molecular, and physiological changes accompanying
      bile acid pool size restoration in Cyp7a1(-/-) mice fed low levels of cholic
      acid.
AB  - Cholesterol 7alpha-hydroxylase (CYP7A1) is the initiating and rate-limiting
      enzyme in the neutral pathway that converts cholesterol to primary bile acids
      (BA). CYP7A1-deficient (Cyp7a1(-/-)) mice have a depleted BA pool, diminished
      intestinal cholesterol absorption, accelerated fecal sterol loss, and increased
      intestinal cholesterol synthesis. To determine the molecular and physiological
      effects of restoring the BA pool in this model, adult female Cyp7a1(-/-) mice and
      matching Cyp7a1(+/+) controls were fed diets containing cholic acid (CA) at
      modest levels [0.015, 0.030, and 0.060% (wt/wt)] for 15-18 days. A level of just
      0.03% provided a CA intake of ~12 MUmol (4.8 mg) per day per 100 g body wt and
      was sufficient in the Cyp7a1(-/-) mice to normalize BA pool size, fecal BA
      excretion, fractional cholesterol absorption, and fecal sterol excretion but
      caused a significant rise in the cholesterol concentration in the small intestine
      and liver, as well as a marked inhibition of cholesterol synthesis in these
      organs. In parallel with these metabolic changes, there were marked shifts in
      intestinal and hepatic expression levels for many target genes of the BA sensor
      farnesoid X receptor, as well as genes involved in cholesterol transport,
      especially ATP-binding cassette (ABC) transporter A1 (ABCA1) and ABCG8. In
      Cyp7a1(+/+) mice, this level of CA supplementation did not significantly disrupt
      BA or cholesterol metabolism, except for an increase in fecal BA excretion and
      marginal changes in mRNA expression for some BA synthetic enzymes. These findings
      underscore the importance of using moderate dietary BA levels in studies with
      animal models.

PMID- 22628036
TI  - A high-affinity and specific carrier-mediated mechanism for uptake of thiamine
      pyrophosphate by human colonic epithelial cells.
AB  - All mammals require exogenous sources of thiamine (vitamin B1), as they lack the
      ability to synthesize the vitamin. These sources are dietary and bacterial (the
      latter is in reference to the vitamin, which is synthesized by the normal
      microflora of the large intestine). Bacterially generated thiamine exists in the
      free, as well as the pyrophosphorylated [thiamine pyrophosphate (TPP)], form.
      With no (or very little) phosphatase activity in the colon, we hypothesized that
      the bacterially generated TPP can also be taken up by colonocytes. To test this
      hypothesis, we examined [(3)H]TPP uptake in the human-derived, nontransformed
      colonic epithelial NCM460 cells and purified apical membrane vesicles isolated
      from the colon of human organ donors. Uptake of TPP by NCM460 cells occurred
      without metabolic alterations in the transported substrate and 1) was pH- and
      Na(+)-independent, but energy-dependent, 2) was saturable as a function of
      concentration (apparent K(m) = 0.157 +/- 0.028 MUM), 3) was highly specific for
      TPP and not affected by free thiamine (or its analogs) or by thiamine
      monophosphate and unrelated folate derivatives, 4) was adaptively regulated by
      extracellular substrate (TPP) level via what appears to be a transcriptionally
      mediated mechanism(s), and 5) appeared to be influenced by an intracellular
      Ca(2+)/calmodulin-mediated regulatory pathway. These findings suggest the
      involvement of a carrier-mediated mechanism for TPP uptake by colonic NCM460
      cells, which was further confirmed by results from studies of native human
      colonic apical membrane vesicles. The results also suggest that the bacterially
      synthesized TPP in the large intestine is bioavailable and may contribute to
      overall body homeostasis of vitamin B1 and, especially, to the cellular nutrition
      of the local colonocytes.

PMID- 22628037
TI  - Activation of the MyD88 signaling pathway inhibits ischemia-reperfusion injury in
      the small intestine.
AB  - Toll-like receptors (TLRs) recognize microbial components and trigger the
      signaling cascade that activates innate and adaptive immunity. Recent studies
      have shown that the activation of TLR-dependent signaling pathways plays
      important roles in the pathogenesis of ischemia-reperfusion (I/R) injuries in
      many organs. All TLRs, except TLR3, use a common adaptor protein, MyD88, to
      transduce activation signals. We investigated the role of MyD88 in I/R injury of
      the small intestine. MyD88 and cyclooxygenase-2 (COX-2) knockout and wild-type
      mice were subjected to intestinal I/R injury. I/R-induced small intestinal injury
      was characterized by infiltration of inflammatory cells, disruption of the
      mucosal epithelium, destruction of villi, and increases in myeloperoxidase
      activity and mRNA levels of TNF-alpha and the IL-8 homolog KC. MyD88 deficiency
      worsened the severity of I/R injury, as assessed using the histological grading
      system, measuring luminal contents of hemoglobin (a marker of intestinal
      bleeding), and counting apoptotic epithelial cells, while it inhibited the
      increase in mRNA expression of TNF-alpha and KC. I/R significantly enhanced COX-2
      expression and increased PGE(2) concentration in the small intestine of wild-type
      mice, which were markedly inhibited by MyD88 deficiency. COX-2 knockout mice were
      also highly susceptible to intestinal I/R injury. Exogenous PGE(2) reduced the
      severity of injury in both MyD88 and COX-2 knockout mice to the level of wild
      type mice. These findings suggest that the MyD88 signaling pathway may inhibit
      I/R injury in the small intestine by inducing COX-2 expression.

PMID- 22628038
TI  - Microwave-assisted solvent-free synthesis and in vitro antibacterial screening of
      quinoxalines and pyrido[2, 3b]pyrazines.
AB  - We report herein the microwave assisted synthesis, without solvents and
      catalysts, of 6-substituted quinoxalines and 7-substituted pyrido[2,3b]pyrazines.
      The compounds were obtained in good yields and short reaction times using the
      mentioned procedure and two new structures are reported. A complete 1H- and 13C
      NMR assignment was performed using 1D and 2D-NMR. Additionally, an in vitro
      screening was performed on Gram-positive and Gram-negative bacteria using
      amoxicillin as positive reference. Compounds bearing a pyridyl group tended to
      have higher antibacterial activity, but the best activity against Bacillus
      subtilis and Proteus mirabilis was observed with quinoxaline derivatives.

PMID- 22628039
TI  - Synthesis of electronically modified Ru-based neutral 16 VE allenylidene olefin
      metathesis precatalysts.
AB  - Electronic modifications within Ru-based olefin metathesis precatalysts have
      provided a number of new complexes with significant differences in reactivity
      profiles. So far, this aspect has not been studied for neutral 16 VE
      allenylidenes. The first synthesis of electronically altered complexes of this
      type is reported. Following the classical dehydration approach (vide infra)
      modified propargyl alcohols were transformed to the targeted allenylidene systems
      in the presence of PCy3. The catalytic performance was investigated in RCM
      reaction (ring closing metathesis) of benchmark substrates such as
      diallyltosylamide and diethyl diallylmalonate.

PMID- 22628040
TI  - Diterpenoid alkaloids from the Chinese traditional herbal "Fuzi" and their
      cytotoxic activity.
AB  - Ten diterpenoid alkaloids, including eight aconitine-type C19-diterpenoid
      alkaloids and two hetisine-type C20-diterpenoid alkaloids, were isolated from the
      secondary roots of Aconitum carmichaeli Debx., known as "Fuzi" in Chinese
      traditional herbal medicine. Their structures were established on the basis of
      their spectroscopic data and comparison with those of the literature. Among these
      alkaloids, chasmanine, oxonitine and 15-acetylsongoramine were isolated for the
      first time from this medicinal plant. The cytotoxic activity of the alkaloids
      were tested against several cell lines by the MTT method in which aconitine,
      hypaconitine, mesaconitne and oxonitine were found to strongly inhibit the growth
      of the HePG2 cell line, which showed that the existence and quantity of the ester
      groups have a significant influence on the cytotoxicity of the diterpenoid
      alkaloids.

PMID- 22628041
TI  - Impact of elevated carbon dioxide on primary, secondary metabolites and
      antioxidant responses of Eleais guineensis Jacq. (oil palm) seedlings.
AB  - A split plot 3 by 3 experiment was designed to investigate the relationships
      among production of primary metabolites (soluble sugar and starch), secondary
      metabolites (total flavonoids, TF; total phenolics, TP), phenylalanine lyase
      (PAL) activity (EC 4.3.1.5), protein and antioxidant activity (FRAP) of three
      progenies of oil palm seedlings, namely Deli AVROS, Deli Yangambi and Deli URT,
      under three levels of CO2 enrichment (400, 800 and 1,200 MUmol.mol-1) for 15
      weeks of exposure. During the study, the treatment effects were solely
      contributed by CO2 enrichment levels; no progenies and interaction effects were
      observed. As CO2 levels increased from 400 to 1,200 MUmol.mol-1, the production
      of carbohydrate increased steadily, especially for starch more than soluble
      sugar. The production of total flavonoids and phenolics contents, were the
      highest under 1,200 and lowest at 400 MUmol.mol-1. It was found that PAL activity
      was peaked under 1,200 MUmol.mol-1 followed by 800 MUmol.mol-1 and 400 MUmol.mol
      1. However, soluble protein was highest under 400 MUmol.mol-1 and lowest under
      1,200 MUmol.mol-1. The sucrose/starch ratio, i.e., the indication of sucrose
      phosphate synthase actvity (EC 2.4.1.14) was found to be lowest as CO2
      concentration increased from 400 > 800 > 1,200 MUmol.mol-1. The antioxidant
      activity, as determined by the ferric reducing/antioxidant potential (FRAP)
      activity, increased with increasing CO2 levels, and was significantly lower than
      vitamin C and alpha-tocopherol but higher than butylated hydroxytoluene (BHT).
      Correlation analysis revealed that nitrogen has a significant negative
      correlation with carbohydrate, secondary metabolites and FRAP activity indicating
      up-regulation of production of carbohydrate, secondary metabolites and
      antioxidant activity of oil palm seedling under elevated CO2 was due to reduction
      in nitrogen content in oil palm seedling expose to high CO2 levels.

PMID- 22628042
TI  - Benzyl 2-beta-glucopyranosyloxybenzoate, a new phenolic acid glycoside from
      Sarcandra glabra.
AB  - From the whole plant of Sarcandra glabra, a new phenolic acid glycoside, benzyl 2
      beta-glucopyranosyloxybenzoate (1), together with seven known compounds including
      eleutheroside B1 (2), 5-O-caffeoylshikimic acid (3), (-)-(7S, 8R)
      dihydrodehydrodiconiferyl alcohol (4), (-)-(7S, 8R)-dihydrodehydrodiconiferyl
      alcohol 9-, 9'- and 4-O-alpha-D-glucopyranoside (5-7), and (-)-(7S, 8R)-5
      methoxydihydrodehydrodiconiferyl alcohol 4-O-beta-D-glucopyranoside (8) was
      isolated. Their structures were elucidated by spectral analysis including 1D-, 2D
      NMR and HR-ESI-MS. Compound 2 was found to exhibit potent cytotoxic activity
      against BGC-823 and A2780 cancer cell lines using MTT method with IC50 value of
      2.53 and 1.85 MUM, respectively.

PMID- 22628043
TI  - Antifungal activities of new coumarins.
AB  - Newly synthesized coumarins 4-((5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)
      methoxy)-2H-chromen-2-one and 4-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)-methoxy)
      2H-chromen-2-one were tested against selected types of fungi and showed
      significant activities. DFT calculations of the synthesized coumarins were
      performed using molecular structures with optimized geometries. Molecular orbital
      calculations provide a detailed description of the orbitals, including spatial
      characteristics, nodal patterns, and the contributions of individual atoms.

PMID- 22628044
TI  - Synthesis of a 2,2'-bipyridyl functionalized oligovinylene-phenylene using Heck
      and Horner-Wadsworth-Emmons reactions and X-ray crystal structure of E-(4-(4
      bromostyryl)phenyl)(methyl)sulfane.
AB  - The synthesis of a new 2,2'-bipyridyl functionalized oligovinylenephenylene (OVP
      5) containing a methyl protected thiol using Heck coupling and the Horner
      Wadsworth-Emmons reaction and is described. A key step involving a
      diisopropylcarbodiimide promoted dehydration of a stable beta-hydroxyphosphonate
      intermediate was identified. The structure of precursor E-(4-(4
      bromostyryl)phenyl)(methyl)sulfane was determined using X-ray crystallography.

PMID- 22628045
TI  - Effect of some biopolymers on the rheological behavior of surimi gel.
AB  - The objective of this study was to investigate the effect of selected biopolymers
      on the rheological properties of surimi. In our paper, we highlight the
      functional properties and rheological aspects of some starch mixtures used in
      surimi. However, the influence of some other ingredients, such as
      cryoprotectants, mannans, and hydroxylpropylmethylcellulose (HPMC), on the
      rheological properties of surimi is also described. The outcome reveals that
      storage modulus increased with the addition of higher levels of starch. Moreover,
      the increasing starch level increased the breaking force, deformation, and gel
      strength of surimi as a result of the absorption of water by starch granules in
      the mixture to make the surimi more rigid. On the other hand, the addition of
      cryoprotectants, mannans, and HPMC improved the rheological properties of surimi.
      The data obtained in this paper could be beneficial particularly to the
      scientists who deal with food processing field.

PMID- 22628046
TI  - Anticancer properties and phenolic contents of sequentially prepared extracts
      from different parts of selected medicinal plants indigenous to Malaysia.
AB  - Different parts of four edible medicinal plants (Casearia capitellata, Baccaurea
      motleyana, Phyllanthus pulcher and Strobilanthus crispus), indigenous to
      Malaysia, were extracted in different solvents, sequentially. The obtained 28
      extracts were evaluated for their in vitro anticancer properties, using the MTS
      assay, on four human cancer cell lines: colon (HT-29), breast (MCF-7), prostate
      (DU-145) and lung (H460) cancers. The best anticancer activity was observed for
      the ethyl acetate (EA) extract of Casearia capitellata leaves on MCF-7 cell lines
      with IC50 2.0 MUg/mL and its methanolic (MeOH) extract showed an outstanding
      activity against lung cancer cell lines. Dichloromethane (DCM) extract of
      Phyllanthus pulcher aerial parts showed the highest anticancer activity against
      DU-145 cell lines, while significant activity was exhibited by DCM extract of
      Phyllanthus pulcher roots on colon cancer cell lines with IC50 value of 8.1
      MUg/mL. Total phenolic content (TPC) ranged over 1-40 mg gallic acid equivalents
      (GAE)/g. For all the samples, highest yields of phenolics were obtained for MeOH
      extracts. Among all the extracts analyzed, the MeOH extracts of Strobilanthus
      crispus leaves exhibited the highest TPC than other samples (p < 0.05). This
      study shows that the nature of phenol determines its anticaner activity and not
      the number of phenols present.

PMID- 22628047
TI  - Protective effects of extracts and flavonoids isolated from Scutia buxifolia
      Reissek against chromosome damage in human lymphocytes exposed to hydrogen
      peroxide.
AB  - Flavonoids are claimed to protect against cardiovascular disease, certain forms
      of cancer and ageing, possibly by preventing initial DNA damage. Therefore, we
      investigated the protective effects of crude extract, ethyl acetate fraction and
      flavonoids (quercetin, quercitrin, isoquercitrin and rutin) isolated from the
      leaves from Scutia buxifolia against chromosome damage induced by H2O2 in human
      lymphocytes by analyzing cellular growth rate, cell viability, mitotic index and
      chromosomal instability. We found a differential response among the compounds
      tested, with the ethyl acetate fraction being more effective than the crude
      extract, a difference perhaps related to the presence of the antioxidants
      identified and quantified by HPLC/DAD. In general, quercetin, isoquercitrin and
      rutin recovered the mitotic index and chromosomal instability more than
      quercitrin after treatment with hydrogen peroxide.

PMID- 22628048
TI  - Near-surface spectrally stable nitrogen vacancy centres engineered in single
      crystal diamond.
AB  - A method for engineering thin (<100 nm) layers of homoepitaxial diamond
      containing high quality, spectrally stable, isolated nitrogen-vacancy (NV)
      centres is reported. The photoluminescence excitation linewidth of the engineered
      NVs are as low as 140 MHz, at temperatures below 12 K, while the spin properties
      are at a level suitable for quantum memory and spin register applications. This
      methodology of NV fabrication is an important step toward scalable and practical
      diamond based photonic devices suitable for quantum information processing.

PMID- 22628049
TI  - Combined posterior and anterior approach to the superior mesenteric artery: the
      advantages of the "hanging maneuver".

PMID- 22628050
TI  - Roles of planar cell polarity signaling in maturation of neuronal precursor cells
      in the postnatal mouse olfactory bulb.
AB  - Neuronal precursor cells generated by stem cells in the subventricular zone (SVZ)
      migrate and differentiate into mature interneurons in the olfactory bulb (OB).
      The mechanisms responsible for the dynamic morphological changes in cells during
      this process are largely unknown. Wnt/planar cell polarity (PCP) signaling
      regulates various developmental events, including neuronal migration and neurite
      formation. Here, we studied the function of two components of the PCP pathway,
      Dishevelled2 and Van Gogh like-2, in the newborn neurons in the postnatal mouse
      OB. Electroporation- or lentivirus-mediated introduction of vectors carrying a
      knockdown or dominant-negative construct of these genes into the SVZ altered the
      distribution and dendrite formation of newborn neurons in the OB, suggesting that
      PCP signaling is involved in regulating the maturation of new neurons in the OB.

PMID- 22628051
TI  - Intrinsic signal optical imaging evidence for dorsal V3 in the prosimian galago
      (Otolemur garnettii).
AB  - Currently, we lack consensus regarding the organization along the anterior border
      of dorsomedial V2 in primates. Previous studies suggest that this region could be
      either the dorsomedial area, characterized by both an upper and a lower visual
      field representation, or the dorsal aspect of area V3, which only contains a
      lower visual field representation. We examined these proposals by using optical
      imaging of intrinsic signals to investigate this region in the prosimian galago
      (Otolemur garnettii). Galagos represent the prosimian radiation of surviving
      primates; cortical areas that bear strong resemblances across members of primates
      provide a strong argument for their early origin and conserved existence. Based
      on our mapping of horizontal and vertical meridian representations, visuotopy,
      and orientation preference, we find a clear lower field representation anterior
      to dorsal V2 but no evidence of any upper field representation. We also show
      statistical differences in orientation preference patches between V2 and V3. We
      additionally supplement our imaging results with electrode array data that reveal
      differences in the average spatial frequency preference, average temporal
      frequency preference, and sizes of the receptive fields between V1, V2, and V3.
      The lack of upper visual field representation along with the differences between
      the neighboring visual areas clearly distinguish the region anterior to dorsal V2
      from earlier visual areas and argue against a DM that lies along the dorsomedial
      border of V2. We submit that the region of the cortex in question is the dorsal
      aspect of V3, thus strengthening the possibility that V3 is conserved among
      primates.

PMID- 22628053
TI  - Can ischemia and dyssynchrony be detected during early stages of dobutamine
      stress echocardiography by 2-dimensional speckle tracking echocardiography?
AB  - Strain and strain rate (SR) measured with 2-dimensional speckle tracking
      echocardiography (2-D STE) can quantitatively assess myocardial function. Our aim
      was to evaluate whether we could detect abnormalities in strain, strain rate, and
      dyssynchrony by applying 2-D STE in patients with severe coronary artery disease
      during early stages of dobutamine stress echocardiography. Thirty-four patients
      with angiographically documented severe 3-vessel coronary artery disease and
      preserved left ventricular ejection fraction were compared with 42 control
      patients without evidence of coronary artery disease. Circumferential and
      longitudinal strain, SR, and left ventricular synchrony using standard deviation
      (SD) of time to systolic peak strain and SR were analyzed with 2-D STE at rest
      and at intermediate doses of dobutamine stress echocardiography. Compared with
      control subjects, patients with coronary artery disease showed lower
      circumferential SR [-1.42 (0.34) s(-1) vs -1.64 (0.34) s(-1); P < .02] and
      significantly lower longitudinal strain [-15.41% (3.52%) vs -19.37% (3.21%); P <
      .001] and SR [-0.91 (0.18) s(-1) vs -1.19 (0.24) s(-1); P < .001] at intermediate
      doses; these values were also compromised at peak dose. The SD of longitudinal
      time to systolic peak strain at intermediate dose was significantly greater in
      patients with coronary artery disease than in control patients [37.89 (12.32) vs
      27.21 (10.86); P < .001]. The 2-D STE-derived strain and SR detected myocardial
      dysfunction and asynchrony in patients with coronary artery disease during
      intermediate doses of dobutamine stress, with minimal changes in regional wall
      motion abnormalities at this stage.

PMID- 22628052
TI  - Accuracy of chest radiography for evaluating significantly abnormal pulmonary
      vascularity in children with congenital heart disease.
AB  - The purpose is to determine the accuracy of chest radiography for evaluating
      significantly abnormal pulmonary vascularity in children with congenital heart
      disease. This retrospective study included 120 children. Forty pediatric
      congenital heart disease patients with a ratio of pulmonary to systemic blood
      flow (Qp:Qs) lower than 0.8 by cardiac catheterization were enrolled as the
      decreased pulmonary vascularity group. Another forty pediatric congenital heart
      disease patients with a Qp:Qs higher than 1.5 were enrolled as the increased
      pulmonary vascularity group. Forty pediatric patients who had no cardiopulmonary
      problems were enrolled as the normal control group. All chest radiographs were
      reviewed by three readers. The results were compared to cardiac catheterization
      as a gold standard. Linear weighted kappa test was used to determine intra- and
      inter-observer agreements. The accuracy, specificity, positive predictive value,
      and negative predictive value of chest radiography to characterize pulmonary
      vascularity patterns in the three groups were moderate to high, falling between
      73 and 92 %, 61 and 96 %, 71 and 94 %, and 71 and 98 %, respectively. The
      sensitivity of chest radiography to interpret decreased pulmonary vascularity
      patterns was low (24-68 %), whereas the sensitivity to interpret normal and
      increased pulmonary vascularity patterns were high (84-94 %). The inter-observer
      agreement was moderate to good (k = 0.53-0.67). The intra-observer reliability
      was good (k = 0.71-0.79). Pediatric chest radiography exhibits good accuracy and
      reproducibility to identify significantly abnormal pulmonary vascularity in
      children with congenital heart disease. However, the sensitivity to detect
      decreased pulmonary vascularity pattern is low.

PMID- 22628054
TI  - Inflammatory markers in coronary artery disease.
AB  - Coronary artery disease (CAD) is one of the most common manifestations of
      atherosclerosis. Inflammation is considered one of the major processes that
      contribute to atherogenesis. Inflammation plays an important role not only on the
      initiation and progression of atherosclerosis but also on plaque rupture, an
      event that leads to acute vascular events. Various biomarkers express different
      pathways and pathophysiologic mechanisms of cardiovascular disease, and
      inflammatory biomarkers express different parts of the atherogenic process,
      regarding the initiation and progression of atherosclerosis or the
      destabilization of the atherosclerotic plaque. Therefore, inflammatory biomarkers
      may prove to be useful in the detection, staging, and prognosis of patients with
      CAD. Furthermore, the fact that inflammatory processes are essential steps in the
      course of the disease offers future therapeutic targets for the interruption of
      the atherogenic process or for the management of acute events.

PMID- 22628055
TI  - Improved parallel MR imaging using a coefficient penalized regularization for
      GRAPPA reconstruction.
AB  - A novel coefficient penalized regularization method for generalized
      autocalibrating partially parallel acquisitions (GRAPPA) reconstruction is
      developed for improving MR image quality. In this method, the fitting
      coefficients of the source data are weighted with different penalty factors,
      which are highly dependent upon the relative displacements from the source data
      to the target data in k-space. The imaging data from both phantom testing and in
      vivo MRI experiments demonstrate that the coefficient penalized regularization
      method in GRAPPA reconstruction is able to reduce noise amplification to a
      greater degree. Therefore, the method enhances the quality of images
      significantly when compared to the previous least squares and Tikhonov
      regularization methods.

PMID- 22628056
TI  - Antitumor effects of somatostatin analogs in neuroendocrine tumors.
AB  - BACKGROUND: For decades, somatostatin analogs (including octreotide and
      lanreotide) have been indicated for relief of the symptoms of flushing, diarrhea,
      and wheezing associated with secretory neuroendocrine tumors (NETs). Recently, it
      has been suggested that somatostatin analogs may provide direct and indirect
      antitumor effects in secretory and nonsecretory NETs in addition to symptom
      control in secretory NETs. METHODS: A systematic review of MEDLINE was conducted
      to identify studies that investigated the antitumor effects of octreotide or
      lanreotide for patients with NETs. Additional studies not published in the peer
      reviewed literature were identified by searching online abstracts. Results. In
      all, 17 octreotide trials and 11 lanreotide trials that included antitumor
      effects were identified. Partial response rates were between 0% and 31%, and
      stable disease rates were between 15% and 89%. Octreotide was the only
      somatostatin analog for which results of a phase III, randomized, placebo
      controlled clinical trial that investigated antitumor effects were published.
      After 6 months of treatment in this randomized phase III trial, stable disease
      was observed in 67% of patients (hazard ratio for time to disease progression:
      0.34; 95% confidence interval: 0.20-0.59; p = .000072). CONCLUSIONS: In addition
      to symptom control for NETs, the data support an antitumor effect of somatostatin
      analogs and suggest that they may slow tumor growth. Long-acting repeatable
      octreotide has been shown to have an antitumor effect in a randomized phase III
      trial in midgut NETs, whereas results are pending in a corresponding controlled
      trial with lanreotide for patients with intestinal and pancreatic primary NETs.

PMID- 22628059
TI  - Fatal hemodialysis in head injured patient.

PMID- 22628058
TI  - The effect of fetal and early postnatal iron deficiency on iron metabolism in
      adult rats.
AB  - Undernutrition during pregnancy and/or lactation plays an important role on the
      overall health of offspring later in life. Using a rodent model, the present
      study was conducted to examine the effect of fetal and early postnatal iron
      deficiency on iron metabolism in adult animals. Rats were treated with three
      stages of low or normal iron diets from gestation until the end of the study.
      During the first stage (4 weeks prior to 3 weeks after pregnancy, total 7 weeks),
      two groups of adult females (dams) were fed with either a low-iron (7.4 mg
      iron/kg, group LD) or control-iron (274 mg/kg, group CD) diet. During the second
      stage (from 3 to 13 weeks of age, total 10 weeks), all pups from stage 1 (both
      the LD and CD groups) were placed on a control-iron diet for 10 weeks (groups LD
      CD and CD-CD, respectively). During the third stage (from 13 to 29 weeks of age,
      total 16 weeks), both LD-CD and CD-CD groups from stage 2 were fed with a low
      iron (named LD-CD-LD and CD-CD-LD groups, respectively). We found that the live
      birth rate of the offspring of the LD dams (84.7 %) was significantly lower than
      that of the CD dams (95.4 %). During stage 2, the mean body weight of the LD-CD
      male or LD-CD female rats exceeded the CD-CD male rats (p < 0.05). Compared with
      the CD-CD-LD rats, the LD-CD-LD rats had significantly increased total iron
      binding capacity, and higher levels of transferrin, serum erythropoietin (EPO),
      renal EPO mRNA, duodenal divalent metal transporter-1, and renal transferrin
      receptors. These findings indicate that rats with an early-life experience of
      iron deficiency (during pregnancy and the nursing period) can develop stronger
      iron absorption capabilities in adulthood.

PMID- 22628060
TI  - Edoxaban administration following enoxaparin: a pharmacodynamic, pharmacokinetic,
      and tolerability assessment in human subjects.
AB  - Edoxaban is an oral direct factor (F)Xa inhibitor in advanced stages of clinical
      development. The primary objective of the present study was to assess the
      pharmacodynamics (PD) and safety of enoxaparin 1 mg/kg followed 12 hours (h) post
      dose by edoxaban 60 mg, which is the regimen being used in the phase III study of
      edoxaban for the treatment of venous thromboembolism (Hokusai-VTE). This was a
      phase I, open-label, randomised, four-period, four-treatment cross-over study.
      Treatments were edoxaban alone (EDOX), enoxaparin alone (ENOX), edoxaban plus
      enoxaparin (EDOX+ENOX), and enoxaparin followed by edoxaban 12 h later (ENOX12
      EDOX). Serial blood samples were collected for PD (thrombin generation, anti-FXa)
      and pharmacokinetic (PK) variables (edoxaban and its principal metabolite M4 by
      LC-MS/MS, and anti-FIIa as a surrogate of enoxaparin). The highest effect on
      thrombin AUC (endogenous thrombin potential, or ETP), thrombin (peak), thrombin
      generation lag time, and velocity index was observed for EDOX+ENOX, followed by
      ENOX, ENOX12-EDOX, and EDOX. The greatest effect on anti-FXa activity was
      observed for EDOX+ENOX, followed by ENOX12-EDOX. As expected, neither edoxaban
      nor enoxaparin significantly altered the PK of the other drug. There were no
      serious adverse events during the study. It is concluded that a 60-mg dose of
      edoxaban can be safely administered 12 h following enoxaparin 1 mg/kg.

PMID- 22628061
TI  - Propanolol and angiogenesis inhibition in hereditary haemorrhagic telangiectasia.

PMID- 22628062
TI  - Bioequivalence of two formulations of escitalopram.
AB  - Escitalopram, CAS registry number 128196-01-0 is an orally administrated
      selective serotonin reuptake inhibitor (SSRI).The objective of this trial was to
      assess bioequivalence between an escitalopram formulation manufactured by Grupo
      Tecnimede and that of a European reference formulation, while evaluating both
      formulations' tolerability as a secondary objective.24 healthy subjects were
      enrolled in a single centre, randomised, single-dose, open-label, 2-way crossover
      study. Drug levels were determined by reverse liquid chromatography and detected
      by tandem mass spectrometry detection, LC-MS/MS method. Pharmacokinetic
      parameters used for bioequivalence assessment were determined from the drug
      concentration data using non-compartmental analysis.Mean+/-Standard deviation
      (SD) Cmax values were 18.89+/-5.06 ng/mL and 18.45+/-5.05 ng/mL for reference and
      test, respectively. AUClast was 577.16+/-196.20 ng . h/mL after the
      administration of the reference and 577.69+/-220.88 ng . h/mL for the test.
      AUCinf was 595.66+/-203.80 ng . h/mL after the administration of the reference
      596.19+/-235.47 ng . h/mL for the test.The 90% confidence intervals obtained by
      analysis of variance were 92.38-103.38% for Cmax, 94.10-104.37% for AUClast and
      93.80-104.09% for AUCinf, which were within the predefined acceptable range of
      80.00-125.00%. Both formulations were well tolerated, with no major side effects
      and no relevant differences in safety profiles observed between the
      preparations.The design of the study was adequate to determine the
      pharmacokinetic parameters of the test and the reference formulations.
      Bioequivalence between formulations was concluded both in terms of rate and
      extent of absorption.

PMID- 22628063
TI  - The novel phenylpropiophenone derivates induced relaxation of isolated rat aorta.
AB  - Our aim was to define how different chemical properties of newly developed
      phenylpropiophenone derivates (PhPds) influenced their potency and efficacy to
      relax rat aorta. A contribution of ion channels in the PhPds and propafenone
      mechanism of vasodilatation was tested. PhPds were syntethysed by substitution in
      the benzyl moiety with -F, -CH3 or -CF3 groups on the ortho or para position. The
      vasodilatation by PhPds was examined on the rings of rat aorta precontracted with
      phenylephrine. In order to test involvement of voltage-gated Na+ and K+ channels
      and L-type Ca2+ channels in a mechanism of action of PhPds, we used their
      blockers: lidocaine, nifedipine and 4-aminopiridine, respectively. Aorta was more
      sensitive to 5-ortho-trifluoromethyl derivate than to propafenone and other
      PhPds. The 5-para-methyl derivate had lower potency and efficacy than propafenone
      and other PhPds. Lidocaine did not influenced relaxation induced by PhPds, but
      slightly inhibited the effect of propafenone. The 4-aminopiridine only inhibited
      relaxation induced by 5-para-methyl derivate. Nifedipine inhibited relaxation of
      the rat aorta induced by 5-ortho-trifluoromethyl derivate and by propafenone.
      Introduction of 5-ortho-trifluoromethyl and 5-para-methyl group in the benzyl
      moiety of propafenone molecule changed its potency, efficacy and mechanism of
      action in the rat aorta. The 4-aminopiridine- and nifedipine sensitive ion
      channels are involved in mechanism of action of 5-para-methyl and 5-ortho
      trifluoromethyl derivate. The introduction of other tested groups in the benzyl
      moiety does not affect pharmacological properties of the PhPds in relation to
      propafenone.

PMID- 22628064
TI  - As flat as it gets: ultrasmooth surfaces from template-stripping procedures.
AB  - In an experimentally simple replica process, the natural flatness of mica or
      polished silicon wafers can be transferred to metal films, resulting in metal
      surfaces with topographic features in Angstrom dimensions over large areas. Two
      decades after its invention, the template-stripping process continues to appeal
      to scientists from diverse research backgrounds primarily due to its simplicity,
      cost-effectiveness and ability to yield high quality substrates and structures.
      This article introduces the basic construction process for template-stripped
      substrates, and reports on a variety of extensions of the process, including the
      generation of materials contrasts and the design of tailored topographies. It
      also highlights the use of such substrates in a variety of research fields in
      nanoscience and technology ranging from surface force measurement and high
      definition imaging to the self-assembly of model membranes and plasmonics.

PMID- 22628065
TI  - Facial phenotype at different ages and cardiovascular malformations in children
      with Williams-Beuren syndrome: a study from India.
AB  - Williams-Beuren syndrome (WBS) is one of the microdeletion syndromes associated
      with distinct facial features, characteristic behavior phenotype (overfriendly
      behavior), congenital heart disease, and other malformations. Clinical features
      in WBS are age dependent. It is important to be aware of variable age dependent
      phenotype, especially facial phenotype due to its crucial role in diagnosis. Here
      we describe the facial phenotype of WBS at different ages (3 months to 15.1
      years) and congenital heart malformations in 27 patients FISH positive for
      7q11.23 microdeletion.

PMID- 22628066
TI  - Synthesis of iridium complexes bearing {o-(Ph2P)C6H4}(3)E type (E = Si, Ge, and
      Sn) ligand and evaluation of electron donating ability of group 14 elements E.
AB  - Trigonal bipyramidal (TBP) iridium(i) complexes {o-(Ph(2)P)C(6)H(4)}(3)EIr(CO) (E
      = Si: 1-Ir, Ge: 2-Ir, Sn: 3-Ir) comprising group 14 element E were synthesized
      and converted into the corresponding cationic iridium(III) complexes [{o
      (Ph(2)P)C(6)H(4)}(3)EIr(H)(CO)][BF(4)] (E = Si: 4, Ge: 5, Sn: 6) bearing
      octahedral geometry by protonation using (Et(2)OH)(BF(4)). The origin of trans
      labilizing abilities of E was investigated through structural analysis, IR and
      NMR spectroscopic analysis, and density functional theory calculations. Further,
      the electron-donating abilities of E were investigated through proton transfer
      reactions.

PMID- 22628067
TI  - Highly sensitive electrochemical immunoassay for H1N1 influenza virus based on
      copper-mediated amplification.
AB  - A highly sensitive electrochemical immunoassay method for detection of H1N1
      influenza virus with the signal amplification of CuO nanoparticles (NPs) has been
      demonstrated.

PMID- 22628068
TI  - Design of psychosocial factors questionnaires: a systematic measurement approach.
AB  - BACKGROUND: Evaluation of psychosocial factors requires instruments that measure
      dynamic complexities. This study explains the design of a set of questionnaires
      to evaluate work and non-work psychosocial risk factors for stress-related
      illnesses. METHODS: The measurement model was based on a review of literature.
      Content validity was performed by experts and cognitive interviews. Pilot testing
      was carried out with a convenience sample of 132 workers. Cronbach's alpha
      evaluated internal consistency and concurrent validity was estimated by Spearman
      correlation coefficients. RESULTS: Three questionnaires were constructed to
      evaluate exposure to work and non-work risk factors. Content validity improved
      the questionnaires coherence with the measurement model. Internal consistency was
      adequate (alpha = 0.85-0.95). Concurrent validity resulted in moderate
      correlations of psychosocial factors with stress symptoms. CONCLUSIONS:
      Questionnaires' content reflected a wide spectrum of psychosocial factors
      sources. Cognitive interviews improved understanding of questions and dimensions.
      The structure of the measurement model was confirmed.

PMID- 22628069
TI  - Catalyst-free and site-specific one-pot dual-labeling of a protein directed by
      two genetically incorporated noncanonical amino acids.

PMID- 22628070
TI  - Microfibers fabricated by non-covalent assembly of peptide and DNA for viral
      vector encapsulation and cancer therapy.
AB  - Self-assembled amphiphilic peptide units and supercoiled, circular double
      stranded plasmid DNA are used as building blocks to form peptide/DNA fibers for
      virus encapsulation. Since the fiber formation process takes place under ambient
      conditions and is aqueous-based without the use of denaturing organic solvents,
      the bioactivity of viruses is well preserved.

PMID- 22628071
TI  - Dimeric analogs of immunosuppressive decapeptide fragment of ubiquitin.
AB  - Our previous studies revealed that ubiquitin and its decapeptide fragment with
      the LEDGRTLSDY sequence, located on the exposed molecule loop, strongly
      suppressed the immune response. This suggested that the loop may serve as a
      functional epitope of ubiquitin molecule and that a possible mechanism of
      biological action of the synthesized peptides is associated with interfering in
      interactions of ubiquitin with other molecules. Ubiquitin is known to exist in
      oligomeric forms, which can interact with various oligomeric receptors. We
      designed and synthesized new dimeric analogs of the ubiquitin fragment, to probe
      whether dimeric peptides may have higher affinity towards the ubiquitin receptors
      responsible for immunosuppression, which are believed to form oligomeric
      structures. Three dimerization strategies, N-terminus to N-terminus, C-terminus
      to C-terminus, and N-terminus to C-terminus (head-to-tail) via PEG derivatives
      were used to synthesize the dimeric peptides on solid support. In the course of
      our research, we developed a new and straightforward procedure of dimerization
      where alpha-amino groups of the C-terminal lysine residues of two peptide
      fragments were linked by PEG spacer directly on solid support. The effect of
      dimeric analogs on the immunological response was tested in the AFC in vitro
      experiment. The immunological tests showed that the head-to-tail dimerization
      caused a more profound increase in the biological activity than other tested
      dimerization methods. Our results suggest that such orientation of peptide
      components may correspond to orientation of the hypothetic ubiquitin receptors
      responsible for the immunomodulatory activity.

PMID- 22628072
TI  - Neuroanatomical organization of the cholinergic system in the central nervous
      system of a basal actinopterygian fish, the senegal bichir Polypterus senegalus.
AB  - Polypterid bony fishes are believed to be basal to other living ray-finned
      fishes, and their brain organization is therefore critical in providing
      information as to primitive neural characters that existed in the earliest ray
      finned fishes. The cholinergic system has been characterized in more advanced ray
      finned fishes, but not in polypterids. In order to establish which cholinergic
      neural centers characterized the earliest ray-finned fishes, the distribution of
      choline acetyltransferase (ChAT) is described in Polypterus and compared with the
      distribution of this molecule in other ray-finned fishes. Cell groups
      immunoreactive for ChAT were observed in the hypothalamus, the habenula, the
      optic tectum, the isthmus, the cranial motor nuclei, and the spinal motor column.
      Cholinergic fibers were observed in both the telencephalic pallium and the
      subpallium, in the thalamus and pretectum, in the optic tectum and torus
      semicircularis, in the mesencephalic tegmentum, in the cerebellar crest, in the
      solitary nucleus, and in the dorsal column nuclei. Comparison of the data within
      a segmental neuromeric context indicates that the cholinergic system in
      polypterid fishes is generally similar to that in other ray-finned fishes, but
      cholinergic-positive neurons in the pallium and subpallium, and in the thalamus
      and cerebellum, of teleosts appear to have evolved following the separation of
      polypterids and other ray-finned fishes.

PMID- 22628074
TI  - Stroke prevention in atrial fibrillation: managing the risks in light of new oral
      anticoagulants.
AB  - Anticoagulation in patients with atrial fibrillation is essential to reduce
      morbidity and mortality associated with stroke, but at the same time the risk of
      bleeding needs to be carefully considered. There have been many recent
      developments in anticoagulation to improve medical management of these patients.
      CHA(2)DS(2)-VASc and HAS-BLED are two new algorithms that clinicians may use
      prior to initiating anticoagulation to estimate the risk of stroke and bleeding
      in patients with atrial fibrillation. In addition, new classes of oral
      anticoagulants such as direct thrombin inhibitors and selective Factor Xa
      inhibitors have emerged and consist of agents that aim to address many of the
      practical management challenges of warfarin. In this review of the literature,
      results of the clinical trials involving these new agents will be discussed and
      compared, with a focus on the balance between efficacy and safety.

PMID- 22628073
TI  - Inheritance model introduces differential bias in CNV calls between parents and
      offspring.
AB  - Copy Number Variation (CNV) is increasingly implicated in disease pathogenesis.
      CNVs are often identified by statistical models applied to data from single
      nucleotide polymorphism panels. Family information for samples provides
      additional information for CNV inference. Two modes of PennCNV (the Joint-call
      and Posterior-call), which are some of the most well-developed family-based CNV
      calling methods, use a "Joint-model" as a main component. This models all family
      members' CNV states together with Mendelian inheritance. Methods based on the
      Joint-model are used to infer CNV calls of cases and controls in a pedigree,
      which may be compared to each other to test an association. Although benefits
      from the Joint-model have been shown elsewhere, equality of call rates in parents
      and offspring has not been evaluated previously. This can affect downstream
      analyses in studies that compare CNV rates in cases vs. controls in pedigrees. In
      this paper, we show that the Joint-model can introduce different CNV call rates
      among family members in the absence of a true difference. We show that the Joint
      model may analytically introduce differential CNV calls because of asymmetry of
      the model. We demonstrate these differential call rates using single-marker
      simulations. We show that call rates using the two modes of PennCNV also differ
      between parents and offspring in one multimarker simulated dataset and two real
      datasets. Our results advise need for caution in use of the Joint-model calls in
      CNV association studies with family-based datasets.

PMID- 22628075
TI  - The Centers for Mendelian Genomics: a new large-scale initiative to identify the
      genes underlying rare Mendelian conditions.
AB  - Next generation exome sequencing (ES) and whole genome sequencing (WGS) are new
      powerful tools for discovering the gene(s) that underlie Mendelian disorders. To
      accelerate these discoveries, the National Institutes of Health has established
      three Centers for Mendelian Genomics (CMGs): the Center for Mendelian Genomics at
      the University of Washington; the Center for Mendelian Genomics at Yale
      University; and the Baylor-Johns Hopkins Center for Mendelian Genomics at Baylor
      College of Medicine and Johns Hopkins University. The CMGs will provide ES/WGS
      and extensive analysis expertise at no cost to collaborating investigators where
      the causal gene(s) for a Mendelian phenotype has yet to be uncovered. Over the
      next few years and in collaboration with the global human genetics community, the
      CMGs hope to facilitate the identification of the genes underlying a very large
      fraction of all Mendelian disorders; see http://mendelian.org.

PMID- 22628076
TI  - Amyloid-like fibril formation by tachykinin neuropeptides and its relevance to
      amyloid beta-protein aggregation and toxicity.
AB  - Protein aggregation and amyloid formation are associated with both pathological
      conditions in humans such as Alzheimer's disease and native functions such as
      peptide hormone storage in the pituitary secretory granules in mammals. Here, we
      studied amyloid fibrils formation by three neuropeptides namely physalaemin,
      kassinin and substance P of tachykinin family using biophysical techniques
      including circular dichroism, thioflavin T, congo red binding and microscopy. All
      these neuropeptides under study have significant sequence similarity with
      Abeta(25-35) that is known to form neurotoxic amyloids. We found that all these
      peptides formed amyloid-like fibrils in vitro in the presence of heparin, and
      these amyloids were found to be nontoxic in neuronal cells. However, the extent
      of amyloid formation, structural transition, and morphology were different
      depending on the primary sequences of peptide. When Abeta(25-35) and Abeta40 were
      incubated with each of these neuropeptides in 1:1 ratio, a drastic increase in
      amyloid growths were observed compared to that of individual peptides suggesting
      that co-aggregation of Abeta and these neuropeptides. The electron micrographs of
      these co-aggregates were dissimilar when compared with individual peptide fibrils
      further supporting the possible incorporation of these neuropeptides in Abeta
      amyloid fibrils. Further, the fibrils of these neuropeptides can seed the fibrils
      formation of Abeta40 and reduced the toxicity of preformed Abeta fibrils. The
      present study of amyloid formation by tachykinin neuropeptides is not only
      providing an understanding of the mechanism of amyloid fibril formation in
      general, but also offering plausible explanation that why these neuropeptide
      might reduce the cytotoxicity associated with Alzheimer's disease related
      amyloids.

PMID- 22628077
TI  - Oral anticoagulation in chronic kidney disease: A huge challenge.

PMID- 22628078
TI  - Farnesyl pyrophosphate is an endogenous antagonist to ADP-stimulated P2Y12
      receptor-mediated platelet aggregation.
AB  - Farnesyl pyrophosphate (FPP) is an intermediate in cholesterol biosynthesis, and
      it has also been reported to activate platelet LPA (lysophosphatidic acid)
      receptors. The aim of this study was to investigate the role of extracellular FPP
      in platelet aggregation. Human platelets were studied with light transmission
      aggregometry, flow cytometry and [35S]GTPgammaS binding assays. As shown
      previously, FPP could potentiate LPA-stimulated shape change. Surprisingly, FPP
      also acted as a selective insurmountable antagonist to ADP-induced platelet
      aggregation. FPP inhibited ADP-induced expression of P-selectin and the activated
      glycoprotein (Gp)IIb/IIIa receptor. FPP blocked ADP-induced inhibition of cAMP
      accumulation and [35S]GTPgammaS binding in platelets. In Chinese hamster ovary
      cells expressing the P2Y12 receptor, FPP caused a rightward shift of the
      [35S]GTPgammaS binding curve. In Sf9 insect cells expressing the human P2Y12
      receptor, FPP showed a concentration-dependent, although incomplete inhibition of
      [3H]PSB-0413 binding. Docking of FPP in a P2Y12 receptor model revealed molecular
      similarities with ADP and a good fit into the binding pocket for ADP. In
      conclusion, FPP is an insurmountable antagonist of ADP-induced platelet
      aggregation mediated by the P2Y12 receptor. It could be an endogenous
      antithrombotic factor modulating the strong platelet aggregatory effects of ADP
      in a manner similar to the use of clopidogrel, prasugrel or ticagrelor in the
      treatment of ischaemic heart disease.

PMID- 22628079
TI  - Spinal cord cavernoma--operative strategy and results in 30 patients.
AB  - BACKGROUND: Many case reports and small series addressing the surgical management
      of spinal cord cavernoma have been published. However, only few larger series
      that would allow identifying operative strategies exist. After having treated 30
      patients, we feel encouraged to report our experiences. METHODS: A total of 30
      patients (13 men and 17 women) were mainly admitted to our institution because of
      sensory deficits (83.3%), paresis (33.3%), and bladder dysfunction (26.6%).
      Magnetic resonance imaging revealed a spinal cavernoma mostly in the thoracic
      region (63.3%). All patients underwent surgery. The relation between pial surface
      and cavernoma guided the choice of approach and the myelotomy site. RESULTS:
      After laminectomy/laminoplasty, median myelotomy was done in 16.7% to reach a
      medially located cavernoma. In 60.0%, myelotomy was located at the dorsal root
      entry zone, for which a (partial) hemilaminectomy was sufficient. The laterality
      of the location guided the bony approach in the remaining 23.3% with exophytic
      cavernoma. Immediately after surgery, neurological worsening was seen in 56.7%,
      an improvement in 10.0% and an unchanged neurological status in 33.3%. During the
      follow-up, the rate of neurological worsening dropped to 10.0%, the improvement
      rate increased to 50.0%. In 40.0% of the patients, the symptoms remained
      unchanged or returned to preoperative status. CONCLUSION: The exact localization
      in relation to the pial surface guides the approach and area of myelotomy. In the
      majority of patients limited approaches are sufficient for successful cavernoma
      removal. In our series anterior approaches had not been necessary.

PMID- 22628080
TI  - Concurrent treatment with BCNU and Gamma Knife radiosurgery in the rat malignant
      glioma model.
AB  - BACKGROUND: Radiosurgery has been shown in a randomized trial not to provide any
      survival benefit for newly diagnosed glioblastoma multiforme (GBM). Nevertheless,
      several institutional retrospective series have supported the role of
      radiosurgery as an adjuvant therapy in GBM. The purpose of this study was to
      investigate the efficacy of concurrent therapy with 1,3 bis[2-chloroethyl]-1
      nitrosourea (BCNU; carmustine) and Gamma Knife radiosurgery (GKRS; Gamma Knife(r)
      Model C, Elekta AB, Stockholm, Sweden) in the C6 rat glioma model. Taken
      together, new therapeutic strategies other than the simple addition of
      radiosurgery deserve to be investigated in the interest of enhancing the effects
      of radiosurgery. MATERIAL AND METHODS: C6 glioma cells of 5 * 105 were
      stereotactically implanted into Sprague-Dawley rats. Tumor volume was measured 2
      weeks later using brain magnetic resonance (MR) imaging and rats were treated
      with BCNU (7 mg/kg, intraperitonial injection), GKRS (20 Gy at 50% isodose line),
      or BCNU followed by GKRS at a 1.5-hour interval. The six surviving rats in each
      group were sacrificed, 2 weeks after treatment. Tumor volume was measured in the
      tissue sections and compared with that measured via MR imaging. Percent volume
      growth was calculated and categorized into one of four groups: progressive
      disease, stable disease, partial response, or complete response. RESULTS: Tumor
      volume significantly increased in all six rats in the control group and decreased
      in all six rats in the BCNU + GKRS group after treatment. Better tumor control
      was observed in the BCNU + GKRS group compared with the control, BCNU, and GKRS
      groups on linear-by-linear association analysis and Fischer's exact test.
      CONCLUSIONS: We suggest that concurrent treatment with BCNU and GKRS is more
      effective in local tumor control compared with GKRS or BCNU alone, in the C6 rat
      glioma model.

PMID- 22628081
TI  - Uncommon lesions in the internal auditory canal (IAC): review of the literature
      and case report.
AB  - BACKGROUND: Despite the relatively frequent occurrence of multiple primary
      tumors, namely, 10% of intracranial tumors, metastasis is a rare occurrence
      within the internal auditory canal (IAC) and cerebellopontine angle (CPA).
      Intracanalicular metastases of adenocarcinoma are documented, but a primary
      adenocarcinoma remains unreported. We provide a review of uncommon lesions in the
      IAC and describe to our knowledge the first instance of a primary adenocarcinoma.
      CASE REPORT: A 60-year-old man presented with nausea and vomiting. Cranial
      computed tomography scan revealed bilateral nonspecific periventricular and
      subcortical vascular lesions. He presented 8 months later with left-sided
      tinnitus, progressive hearing loss, and attacks of vertigo. Magnetic resonance
      imaging (MRI) showed an extra-axial mass most likely representing a left-sided
      vestibular schwannoma with characteristic contrast enhancement in the IAC. The
      follow-up MRI showed an unchanged pattern of contrast enhancement. Due to
      progressive headaches and dizziness, the patient underwent a left transtemporal
      craniotomy with subtotal tumor resection. Histological examination revealed
      blennogenic cylindrical adenocarcinoma. The investigations for the primary tumor
      site were all negative. The patient's condition deteriorated gradually. MRI
      showed an increase of the residual tumor and meningeosis carcinomatosa, and
      cerebrospinal fluid (CSF) examination was positive for tumor cells. The patient
      was treated with intrathecal chemotherapy. He died of multiple organ failure.
      DISCUSSION: The discussion focuses on the incidence of extra-axial CPA and IAC
      lesions with their clinical presentations and their radiological findings. We
      address the issue of a possible regulation of CPA lesion laterality by
      asymmetrically expressed genes. In view of the sparse literature on treatment of
      single intracanalicular metastases, the review is broadened to the current
      treatment recommendations of single brain metastases. CONCLUSIONS: The
      differentiation between benign and malign lesions in the CPA and IAC is
      important, as it requires diverse treatment protocols. For the physician this
      differentiation represents a clinical and radiological challenge. For the
      developmental research the left-right asymmetry might be a field of research.

PMID- 22628082
TI  - A reminder for a very rare entity: massive tongue swelling after posterior fossa
      surgery.
AB  - OBJECTIVE: The purpose of this study is to report a case of presumably neurogenic
      macroglossia that occurred after surgical trapping of a vertebral artery (VA)
      posteroinferior cerebellar artery aneurysm, and to analyze its potential
      pathogenesis. CLINICAL PRESENTATION: A 53-year-old woman who suffered from
      headaches and intermittent loss of consciousness but without evidence of
      subarachnoid hemorrhage was admitted. Magnetic resonance imaging and angiography
      showed an irregular aneurysm in the fourth segment of a left dominant VA.
      INTERVENTION: Surgical treatment was indicated after discussion with the
      neuroradiology team. During surgery, in the prone position the aneurysm ruptured.
      The patient became hemodynamically instable. On the first postoperative day,
      macroglossia appeared and remained for 3 weeks until spontaneous regression.
      CONCLUSION: Macroglossia is a rare complication following neurosurgical
      procedures with very few cases reported so far. It has been attributed to the
      sitting position and venous flow congestion. We illustrate a case of
      macroglossia, which occurred following surgery in the prone position. Its
      etiology remains speculative, but a neurogenic explanation seems most plausible.

PMID- 22628086
TI  - Carbon-nanotube/silver networks in nitrile butadiene rubber for highly conductive
      flexible adhesives.
AB  - An adhesive with high conductivity, flexibility, cyclability, oxidation
      resistance, and good adhesion is developed using microscale silver flakes,
      multiwalled carbon nanotubes decorated with nanoscale silver particles, and
      nitrile butadiene rubber. Light-emitting-diode chips are attached to the
      conductive, flexible adhesive pattern on a poly(ethylene terephthalate) substrate
      as a visual demonstration. The brightness is invariant during bending tests.

PMID- 22628084
TI  - Functional redundancy of the two 5-hydroxylases in monolignol biosynthesis of
      Populus trichocarpa: LC-MS/MS based protein quantification and metabolic flux
      analysis.
AB  - Flowering plants have syringyl and guaiacyl subunits in lignin in contrast to the
      guaiacyl lignin in gymnosperms. The biosynthesis of syringyl subunits is
      initiated by coniferaldehyde 5-hydroxylase (CAld5H). In Populus trichocarpa there
      are two closely related CAld5H enzymes (PtrCAld5H1 and PtrCAld5H2) associated
      with lignin biosynthesis during wood formation. We used yeast recombinant
      PtrCAld5H1 and PtrCAld5H2 proteins to carry out Michaelis-Menten and inhibition
      kinetics with LC-MS/MS based absolute protein quantification. CAld5H, a
      monooxygenase, requires a cytochrome P450 reductase (CPR) as an electron donor.
      We cloned and expressed three P. trichocarpa CPRs in yeast and show that all are
      active with both CAld5Hs. The kinetic analysis shows both CAld5Hs have
      essentially the same biochemical functions. When both CAld5Hs are coexpressed in
      the same yeast membranes, the resulting enzyme activities are additive,
      suggesting functional redundancy and independence of these two enzymes. Simulated
      reaction flux based on Michaelis-Menten kinetics and inhibition kinetics
      confirmed the redundancy and independence. Subcellular localization of both
      CAld5Hs as sGFP fusion proteins expressed in P. trichocarpa differentiating xylem
      protoplasts indicate that they are endoplasmic reticulum resident proteins. These
      results imply that during wood formation, 5-hydroxylation in monolignol
      biosynthesis of P. trichocarpa requires the combined metabolic flux of these two
      CAld5Hs to maintain adequate biosynthesis of syringyl lignin. The combination of
      genetic analysis, absolute protein quantitation-based enzyme kinetics, homologous
      CPR specificity, SNP characterization, and ER localization provides a more
      rigorous basis for a comprehensive systems understanding of 5-hydroxylation in
      lignin biosynthesis.

PMID- 22628087
TI  - The ADOS calibrated severity score: relationship to phenotypic variables and
      stability over time.
AB  - Measurement of the severity of autism at a single time point, and over time, is a
      widespread challenge for researchers. Recently, Gotham, Pickles, and Lord
      published a severity metric (calibrated severity scores; CSS) that takes into
      account age and language level and is based on raw total scores of the Autism
      Diagnostic Observation Schedule (ADOS), a standardized measure commonly used in
      autism diagnosis. The present study examined psychometric characteristics of the
      CSS compared to raw scores in an independent sample of 368 children aged 2 to 12
      years with autism, pervasive developmental disorder-not otherwise specified (PDD
      NOS), non-spectrum delay, or typical development. Reflecting the intended
      calibration, the CSS were more uniformly distributed within clinical diagnostic
      category and across ADOS modules than were raw scores. Cross-sectional analyses
      examining raw and severity scores and their relationships to participant
      characteristics revealed that verbal developmental level was a significant
      predictor of raw score but accounted for significantly less variance in the CSS.
      Longitudinal analyses indicated overall stability of the CSS over 12 to 24 months
      in children with autism. Findings from this study support the use of the CSS as a
      more valid indicator of autism severity than the ADOS raw total score, and extend
      the literature by examining the stability over 12 to 24 months of the CSS in
      children with ASD.

PMID- 22628088
TI  - Cumulative trauma disorders among California veterinarians.
AB  - BACKGROUND: The prevalence of cumulative trauma disorders (CTDs) in veterinarians
      has not been adequately studied. METHODS: A questionnaire was sent to 2,000
      California veterinarians in 1997; the return rate was 73% (n = 1,415). RESULTS:
      Ninety-six percent (1,353) of the respondents were professionally active and were
      included in the analyses. Sixty-four percent were male and 90% were working full
      time. One-fourth of the respondents reported a CTD during their career that
      required treatment or restricted usual activities. Two-thirds of those reporting
      CTDs reported chronic or residual problems. In a multivariate regression analysis
      female sex, working full-time, rectal palpations, and large animal practice were
      significant risk factors for CTDs. CONCLUSIONS: Being in large animal practice
      increased the CTD risk for both women and men whether they worked full or part
      time. CTD risk was highest in women working full-time and doing 80% rectal
      palpations. Preventive methods to attenuate the risk of CTDs especially in large
      animal practice should be investigated.

PMID- 22628089
TI  - Differentiation and assignment of vinyl telluride regioisomers by (1) H-(125) Te
      gHMBC.
AB  - Complete (1) H, (13) C, and (125) Te NMR spectral data for some vinyl tellurides
      are described. The (1) H-(125) Te gHMBC experiment was used for the complete
      chemical shift assignment and structure elucidation of a mixture of regioisomers.
      The assignment ((125) Te NMR) and coupling constants (J(H,H) ) for all
      regioisomers are described for the first time.

PMID- 22628091
TI  - It means everything: continuing normality of everyday life for people with
      rheumatoid arthritis in early remission.
AB  - OBJECTIVE: The aim of this follow-up study was twofold: firstly, to explore how
      people who were clinically regarded to be in a state of remission experienced
      their everyday lives with rheumatoid arthritis (RA); secondly, to explore the
      experiences of people in early remission with healthcare provision and their
      perceived support needs. METHODS: Two focus group interviews were conducted with
      11 participants in total. Interview data were analysed using content analysis
      methods. RESULTS: All participants felt that they were able to continue their
      normal everyday activities at home, at leisure and at work. They were also able
      to maintain their normal roles. Continuing the normality of everyday life seemed
      to be the most important defining variable for experiencing being in remission.
      Support needs were directly related to the participants' positive experiences of
      actual support from the healthcare providers and were related to the continuity
      of the care provider, coherence, being taken care of, having a personal and
      trusting relationship with the health professionals and being properly informed
      about RA and how to manage it. CONCLUSION: The participants wanted to concentrate
      on wellness and tended to avoid thinking of possible side effects, being chronic
      ill and the development of RA in the future.

PMID- 22628090
TI  - Alterations in sulfated chondroitin glycosaminoglycans following controlled
      cortical impact injury in mice.
AB  - Chondroitin sulfate proteoglycans (CSPGs) play a pivotal role in many neuronal
      growth mechanisms including axon guidance and the modulation of repair processes
      following injury to the spinal cord or brain. Many actions of CSPGs in the
      central nervous system (CNS) are governed by the specific sulfation pattern on
      the glycosaminoglycan (GAG) chains attached to CSPG core proteins. To elucidate
      the role of CSPGs and sulfated GAG chains following traumatic brain injury (TBI),
      controlled cortical impact injury of mild to moderate severity was performed over
      the left sensory motor cortex in mice. Using immunoblotting and immunostaining,
      we found that TBI resulted in an increase in the CSPGs neurocan and NG2
      expression in a tight band surrounding the injury core, which overlapped with the
      presence of 4-sulfated CS GAGs but not with 6-sulfated GAGs. This increase was
      observed as early as 7 days post injury (dpi), and persisted for up to 28 dpi.
      Labeling with markers against microglia/macrophages, NG2+ cells, fibroblasts, and
      astrocytes showed that these cells were all localized in the area, suggesting
      multiple origins of chondroitin-4-sulfate increase. TBI also caused a decrease in
      the expression of aggrecan and phosphacan in the pericontusional cortex with a
      concomitant reduction in the number of perineuronal nets. In summary, we describe
      a dual response in CSPGs whereby they may be actively involved in complex repair
      processes following TBI.

PMID- 22628092
TI  - Effect of functional groups on the radial collapse and elasticity of carbon
      nanotubes under hydrostatic pressure.
AB  - The effect of functional groups on the radial collapse and elasticity of a single
      walled carbon nanotube (SWNT) under hydrostatic pressure was investigated using
      molecular dynamics and molecular mechanics simulations. It is found that the
      radial collapse and elasticity of the chemically modified SWNTs strongly depend
      on the polarity of the functional groups and the degree of functionalization. The
      results show that the fluorine modified SWNT (F-SWNT), on which 2.5-5.0% of the
      atoms are attached to -F groups, can sustain the original elasticity of the
      intrinsic SWNT, and the pressure needed to collapse the F-SWNT increases by 11.3
      21.8%. Functional groups such as hydroxyl groups, amino groups and carboxylic
      groups can increase the pressure needed to collapse the modified SWNTs, but
      decrease their radial elasticity. Therefore, the F-SWNTs, due to the higher
      collapse pressure, are ideal fillers for nanocomposites for high load mechanical
      support.

PMID- 22628093
TI  - Radar aeroecology: exploring the movements of aerial fauna through radio-wave
      remote sensing.
AB  - An international and interdisciplinary Radar Aeroecology Workshop was held at the
      National Weather Center on 5-6 March 2012 on the University of Oklahoma campus in
      Norman, OK, USA. The workshop brought together biologists, meteorologists, radar
      engineers and computer scientists from 22 institutions and four countries. A
      central motivation behind the Radar Aeroecology Workshop was to foster better
      communication and cross-disciplinary collaboration among a diverse spectrum of
      researchers, and promote a better understanding of the ecology of animals that
      move within and use the Earth's lower atmosphere (aerosphere).

PMID- 22628094
TI  - Fitness conferred by replaced amino acids declines with time.
AB  - The fitness landscape of a locus, the array of fitnesses conferred by its
      alleles, can be affected by allele replacements at other loci, in the presence of
      epistatic interactions between loci. In a pair of diverging homologous proteins,
      the initially high probability that an amino acid replacement in one of them will
      make it more similar to the other declines with time, implying that the fitness
      landscapes of homologous sites diverge. Here, we use data on within-population
      non-synonymous polymorphisms and on amino acid replacements between species to
      study the dynamics, after an amino acid replacement, of the fitness of the
      ancestral amino acid, and show that selection against its restoration increases
      with time. This effect can be owing to increase of fitness conferred by the new
      amino acid occupying the site, and/or to decline of fitness conferred by the
      replaced amino acid. We show that the fitness conferred by the replaced amino
      acid rapidly declines, reaching a new lower steady-state level after
      approximately 20 per cent of amino acids in the protein get replaced. Therefore,
      amino acid replacements in evolving proteins are routinely involved in negative
      epistatic interactions with currently absent amino acids, and chisel off the
      unused parts of the fitness landscape.

PMID- 22628095
TI  - Street lighting changes the composition of invertebrate communities.
AB  - Artificial lighting has been used to illuminate the nocturnal environment for
      centuries and continues to expand with urbanization and economic development.
      Yet, the potential ecological impact of the resultant light pollution has only
      recently emerged as a major cause for concern. While investigations have
      demonstrated that artificial lighting can influence organism behaviour,
      reproductive success and survivorship, none have addressed whether it is altering
      the composition of communities. We show, for the first time, that invertebrate
      community composition is affected by proximity to street lighting independently
      of the time of day. Five major invertebrate groups contributed to compositional
      differences, resulting in an increase in the number of predatory and scavenging
      individuals in brightly lit communities. Our results indicate that street
      lighting changes the environment at higher levels of biological organization than
      previously recognized, raising the potential that it can alter the structure and
      function of ecosystems.

PMID- 22628096
TI  - Molecular dating of human-to-bovid host jumps by Staphylococcus aureus reveals an
      association with the spread of domestication.
AB  - Host species switches by bacterial pathogens leading to new endemic infections
      are important evolutionary events that are difficult to reconstruct over the long
      term. We investigated the host switching of Staphylococcus aureus over a long
      evolutionary timeframe by developing Bayesian phylogenetic methods to account for
      uncertainty about past host associations and using estimates of evolutionary
      rates from serially sampled whole-genome data. Results suggest multiple jumps
      back and forth between human and bovids with the first switch from humans to
      bovids taking place around 5500 BP, coinciding with the expansion of cattle
      domestication throughout the Old World. The first switch to poultry is estimated
      at around 275 BP, long after domestication but still preceding large-scale
      commercial farming. These results are consistent with a central role for
      anthropogenic change in the emergence of new endemic diseases.

PMID- 22628097
TI  - Diversity-disturbance relationships: frequency and intensity interact.
AB  - An influential ecological theory, the intermediate disturbance hypothesis (IDH),
      predicts that intermediate levels of disturbance will maximize species diversity.
      Empirical studies, however, have described a wide variety of diversity
      disturbance relationships (DDRs). Using experimental populations of microbes, we
      show that the form of the DDR depends on an interaction between disturbance
      frequency and intensity. We find that diversity shows a monotonically increasing,
      unimodal or flat relationship with disturbance, depending on the values of the
      disturbance aspects considered. These results confirm recent theoretical
      predictions, and potentially reconcile the conflicting body of empirical evidence
      on DDRs.

PMID- 22628098
TI  - Testing models of dental development in the earliest bony vertebrates,
      Andreolepis and Lophosteus.
AB  - Theories on the development and evolution of teeth have long been biased by the
      fallacy that chondrichthyans reflect the ancestral condition for jawed
      vertebrates. However, correctly resolving the nature of the primitive vertebrate
      dentition is challenged by a dearth of evidence on dental development in
      primitive osteichthyans. Jaw elements from the Silurian-Devonian stem
      osteichthyans Lophosteus and Andreolepis have been described to bear a dentition
      arranged in longitudinal rows and vertical files, reminiscent of a pattern of
      successional development. We tested this inference, using synchrotron radiation X
      ray tomographic microscopy (SRXTM) to reveal the pattern of skeletal development
      preserved in the sclerochronology of the mineralized tissues. The tooth-like
      tubercles represent focal elaborations of dentine within otherwise continuous
      sheets of the dermal skeleton, present in at least three stacked generations.
      Thus, the tubercles are not discrete modular teeth and their arrangement into
      rows and files is a feature of the dermal ornamentation that does not reflect a
      polarity of development or linear succession. These fossil remains have no
      bearing on the nature of the dentition in osteichthyans and, indeed, our results
      raise questions concerning the homologies of these bones and the phylogenetic
      classification of Andreolepis and Lophosteus.

PMID- 22628099
TI  - Gender- and stressor-specific microRNA expression in Tribolium castaneum.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs mediating post-transcriptional
      regulation of gene expression in eukaryotes. Addressing their role in regulation
      of physiological adaptations to environmental stress in insects, we selected the
      red flour beetle Tribolium castaneum as a model. Beetles were fed with the
      bacterial entomopathogen Pseudomonas entomophila (to mimic natural infection),
      injected with peptidoglycan (experimental setting of strong immune responses) or
      subjected to either mild heat shock or starvation. Differential expression of
      selected immunity- and stress-related genes was quantified using real-time PCR,
      and expression and induction of 455 mature arthropod miRNAs were determined using
      proprietary microarrays. We found that Tribolium exhibits both gender- and
      stressor-specific adjustment of immune gene and miRNA expression. Strikingly, we
      discovered that the number of stressor-induced miRNAs in females is remarkably
      higher than in males. This observation could support the hypothesis called
      Bateman's principle in immunity that predicts gender-specific immune responses
      because females gain fitness through increased longevity, whereas males gain
      fitness by increasing mating rates. Our results suggest that Tribolium males and
      females display differential regulatory elements, both pre- and post
      transcriptional, likely resulting from different investment strategies in life
      history traits.

PMID- 22628100
TI  - Isodicentric Y chromosomes in Egyptian patients with disorders of sex development
      (DSD).
AB  - Isodicentric chromosome formation is the most common structural abnormality of
      the Y chromosome. As dicentrics are mitotically unstable, they are subsequently
      lost during cell division resulting in mosaicism with a 45,X cell line. We report
      on six patients with variable signs of disorders of sex development (DSD)
      including ambiguous genitalia, short stature, primary amenorrhea, and male
      infertility with azoospermia. Cytogenetic studies showed the presence of a sex
      chromosome marker in all patients; associated with a 45,X cell line in five of
      them. Fluorescence in situ hybridization (FISH) technique was used to determine
      the structure and the breakage sites of the markers that all proved to be
      isodicentric Y chromosomes. Three patients, were found to have similar
      breakpoints: idic Y(qter-> p11.32:: p11.32-> qter), two of them presented with
      ambiguous genitalia and were found to have ovotesticular DSD, while the third
      presented with short stature and hypomelanosis of Ito. One female patient
      presenting with primary amenorrhea, Turner manifestations and ambiguous genitalia
      revealed the breakpoint: idic Y (pter->q11.1::q11.1->pter). The same breakpoint
      was detected in a male with azoospermia but in non-mosaic form. An infant with
      ambiguous genitalia and mixed gonadal dysgenesis (MGD) had the breakpoint at
      Yq11.2: idic Y(pter->q11.2::q11.2->pter). SRY signals were detected in all
      patients. Sequencing of the SRY gene was carried out for three patients with
      normal results. This study emphasizes the importance of FISH analysis in the
      diagnosis of patients with DSD as well as the establishment of the relationship
      between phenotype and karyotype.

PMID- 22628101
TI  - Spatial scales of variation in lichens: implications for sampling design in
      biomonitoring surveys.
AB  - The variability of biological data is a main constraint affecting the quality and
      reliability of lichen biomonitoring surveys for estimation of the effects of
      atmospheric pollution. Although most epiphytic lichen bioindication surveys focus
      on between-site differences at the landscape level, associated with the large
      scale effects of atmospheric pollution, current protocols are based on multilevel
      sampling, thus adding further sources of variation and affecting the error
      budget. We test the hypothesis that assemblages of lichen communities vary at
      each spatial scale examined, in order to determine what scales should be included
      in future monitoring studies. We compared four sites in Italy, along gradients of
      atmospheric pollution and climate, to test the partitioning of the variance
      components of lichen diversity across spatial scales (from trunks to landscapes).
      Despite environmental heterogeneity, we observed comparable spatial variance.
      However, residuals often overcame between-plot variability, leading to biased
      estimation of atmospheric pollution effects.

PMID- 22628102
TI  - Monitoring of biophysical parameters of cashew plants in Cambodia using
      ALOS/PALSAR data.
AB  - An accurate estimation of a plant's age is required for the prediction of yield
      and management practices. This study demonstrates the relationship between
      backscattering properties (sigma degrees ) of Phased Array type L-band Synthetic
      Aperture Radar (PALSAR) dual polarimetric data with cashew plants' biophysical
      parameters (height, age, crown diameter, diameter at breast height, basal area,
      tree density, and biomass) in Cambodia. PALSAR sigma degrees  has shown a
      positive correlation with the biophysical parameters of cashew plants. The value
      of sigma degrees  increases with the age of cashew plants. At a young stage, the
      cashew plants show a higher rate of an increase in sigma degrees  compared to
      that at the mature stage. The sigma degrees  horizontal polarization transmitted
      and vertical received (HV) shows higher sensitivity to the plant's growth than
      sigma degrees  horizontal polarization transmitted and received (HH). High
      backscattering and low variations were observed at mature stage (8-12 years) of
      cashew plantation. Saturation in backscattering has shown from the age of about
      13 years. The validation results indicate strong coefficient of determination
      (R(2) = 0.86 and 0.88) for PALSAR-predicted age and biomass of cashew plants with
      root mean square error = 1.8 years and 16.3 t/ha for age and biomass,
      respectively. The correlations of sigma degrees  (HH) with biophysical parameters
      observed in the dry season were better than those of the rainy season because
      soil moisture interferes with backscattering in the rainy season. Biomass
      accumulation rate of cashew plants has been predicted that would be useful for
      selection of plants species to enhance carbon sequestration. This study provides
      an insight to use PALSAR for the monitoring of growth stages of plants at the
      regional level.

PMID- 22628103
TI  - Modeling of lead and cadmium uptake by plants in the presence of surfactants.
AB  - The mechanism of simultaneous uptake of Cd(II) and Pb(II) by Indian mustard
      (Brassica juncea) in presence of Triton X-100 and Tween 80 was investigated. The
      metal uptake data were analyzed according to the linear as well as the nonlinear
      Langmuir- and Freundlich-type models. The modeling efficiency (EF) and the root
      mean square error (RMSE) were used to evaluate the models prediction. Compared to
      the linear and the Langmuir-type models, the Freundlich-type model marginally
      exhibits a better fit for the biosorption of solubilized Cd(II) by surfactants as
      reflected by higher EF and lower RMSE values. The values of observed Pb(II)
      uptake were in close agreement with the predictions of the Freundlich-type model
      than for the Langmuir-type model.

PMID- 22628104
TI  - A very sensitive flow-injection spectrophotometric determination method for iron
      (II) and total iron using 2', 3, 4', 5, 7-pentahydroxyflavone.
AB  - In this study, an ultra-sensitive and highly selective, rapid flow-injection
      spectrophotometric method for the determination of iron (II) and total iron has
      been proposed. The method was based on the reaction between iron (II) and 2', 3,
      4', 5, 7-pentahydroxyflavone in slightly acidic solution with a strong absorption
      at 415 nm. The carrier solution used was 1 * 10(-5) M 2', 3, 4', 5, 7
      pentahydroxyflavone in 0.1 M HAc/Ac(-) buffer solution at pH 4.5. Parameters that
      affect simultaneously the determination of iron (II) and interfering ions were
      tested. The relative standard deviation for the determination of 50 MUg L(-1)
      iron (II) was 0.85 % (n = 10), and the limit of detection (blank signal plus
      three times the standard deviation of the blank) was 3 MUg L(-1), both based on
      injection volumes of 20 MUL. The method has been successfully applied to the
      determination of iron (II) and total iron in water samples and ore samples. The
      method was verified by analysing a certified reference material Zn/Al/Cu 43XZ3F.

PMID- 22628105
TI  - Impacts of restoration of an uncontrolled phosphogypsum dumpsite on the seasonal
      distribution of abiotic variables, phytoplankton, copepods, and ciliates in a man
      made solar saltern.
AB  - The restoration of an uncontrolled phosphogypsum landfill was investigated for
      its effects on the seasonal distribution of phytoplankton, ciliates, and
      copepods. Sampling was carried out monthly from September 2007 to August 2008 at
      four ponds of increasing salinity (A1, 41 psu; A5, 46 psu; A16, 67 psu; and C31,
      77 psu) in the Sfax solar saltern (southeastern Tunisia). Physicochemical and
      biological analyses were carried out using standard methods. Results showed
      drastic reduction of phosphate input and greater diversity of phytoplankton,
      ciliates, and copepods than before restoration. Pennate diatoms and new ciliates,
      considered bio-indicators of less-stressed marine ecosystems, proliferated in the
      A1 pond for the first time after restoration. Copepods appeared to feed on a wide
      range of prey. Economically, removal of the 1.7 million m(3) of phosphate
      improved the quality of the site's salt production, enabling the salt company to
      receive the quality ISO 9001 accreditation.

PMID- 22628106
TI  - Assessment of cylindrospermopsin toxin in an arid Saudi lake containing dense
      cyanobacterial bloom.
AB  - This study reports the presence of the cyanobacterial toxin cylindrospermopisn
      (CYN) and its producer Cylindrospermopsis raciborskii for the first time in Saudi
      freshwater sources. C. raciborskii was found in Gazan Dam Lake water with two
      morphotypes (coiled and straight). The appearance and cell density of this
      species was significantly positively related to high temperature and high
      ammonium concentrations, and negatively with nitrate and phosphate concentrations
      in the lake. Intracellular concentrations of CYN (4-173 MUg L(-1)) were
      associated with C. raciborskii rather than other cyanobacteria with a maximal
      value obtained in June 2011, coinciding with the highest bloom of this species
      (19 * 10(7) trichome L(-1)). CYN cell quotas (0.6-14.6 pg cell(-1)) varied
      significantly along the study period and correlated with most environmental
      factors. The results of ELISA and liquid chromatography-mass spectrometry proved
      that the CYN production by strains of this species was isolated from this lake
      during the present study, with an amount reaching 568 MUg g(-1). Extracellular
      CYN was also detected in cell-free lake water at concentrations 0.03-23.3 MUg L(
      1), exceeding the drinking water guideline value of 1 MUg L(-1) during the Apr
      Jul period. As this lake is an important source for drinking and irrigation
      waters, CYN monitoring should be included in the environmental and health risk
      assessment plans of these water bodies.

PMID- 22628107
TI  - Multivariate analysis of potentially toxic metals in sediments of a tropical
      coastal lagoon.
AB  - Surface sediments collected from the Lagos Lagoon, Nigeria, and three adjoining
      rivers were analysed for their physicochemical properties and pseudo-total
      concentration of the potentially toxic metals (PTM) Cd, Cr, Cu, Pb and Zn. The
      concentration of the PTM varied seasonally and spatially. Odo-Iyaalaro was
      observed to be the most polluted river, with highest concentrations of 42.1 mg
      kg(-1), 102 mg kg(-1), 185 mg kg(-1), 154 mg kg(-1) and 1040 mg kg(-1) of Cd, Cr,
      Cu, Pb and Zn, respectively, while Ibeshe River was the least contaminated, apart
      from a site affected by Cu from the textile industry. Some of the sediments were
      found to be above the consensus-based probable effect concentrations and Dutch
      sediment guideline for metals. Overall metal concentrations were similar to those
      reported for other tropical lagoon and estuarine systems affected by
      anthropogenic inputs as a result of rapid urbanisation. Due to the large number
      of samples, principal component analysis was used to examine relationships within
      the data set. Generally, sediments collected during the dry season were observed
      to have higher concentration of PTM than those collected during the rainy season.
      This means that PTM could accumulate over a prolonged period and then be released
      relatively rapidly, on an annual basis, into tropical lagoon systems.

PMID- 22628108
TI  - Effect of training frequency on maximum expiratory pressure.
AB  - PURPOSE: To determine the effects of expiratory muscle strength training (EMST)
      frequency on maximum expiratory pressure (MEP). METHOD: We assigned 12 healthy
      participants to 2 groups of training frequency (3 days per week and 5 days per
      week). They completed a 4-week training program on an EMST trainer (Aspire
      Products, LLC). MEP was the primary outcome measure used to determine the effect
      of training frequency. RESULTS: Participants who trained 3 days per week produced
      equivalent amounts of improvement in MEP compared with participants who trained 5
      days per week. An overall improvement in MEP over the 4-week training period
      indicated a 33% increase when the data was collapsed across the 2 training
      groups. CONCLUSION: The effects occurring with respiratory muscle strength
      training in healthy young adults are likely to be different from those occurring
      in patient populations. Therefore, the results of the present study suggest
      exploring the variable of training frequency in patient populations. Such
      knowledge will be informative for designing clinical protocols that are effective
      and may result in improved treatment compliance for those suffering from
      expiratory muscle weakness.

PMID- 22628109
TI  - Monitoring progress in vocal development in young cochlear implant recipients:
      relationships between speech samples and scores from the Conditioned Assessment
      of Speech Production (CASP).
AB  - PURPOSE: To determine the concurrent validity of the Conditioned Assessment of
      Speech Production (CASP; Ertmer & Stoel-Gammon, 2008) and data obtained from
      speech samples recorded at the same intervals. METHOD: Nineteen children who are
      deaf who received cochlear implants before their 3rd birthdays participated in
      the study. Speech samples and CASP scores were gathered at 6, 12, 18, and 24
      months postactivation. Correlation analyses were conducted to assess the
      concurrent validity of CASP scores and data from samples. RESULTS: CASP scores
      showed strong concurrent validity with scores from speech samples gathered across
      all recording sessions (6-24 months). CONCLUSIONS: The CASP was found to be a
      valid, reliable, and time-efficient tool for assessing progress in vocal
      development during young cochlear implant recipients' first 2 years of device
      experience.

PMID- 22628110
TI  - Thymosin beta4 and cardiac regeneration: are we missing a beat?
AB  - Epicardial resident stem cells are known to differentiate into cardiomyocytes
      during cardiac development, amongst other cell types. Whether epicardium-derived
      progenitor cells (EPDCs) retain this plasticity in the adult heart has been the
      topic of heated scientific debate. Priming with thymosin beta 4, a peptide which
      has been suggested to be critical for cardiac development and to have cardio
      protective properties, was recently shown to induce differentiation of EPDCs into
      cardiomyocytes in a small animal model of myocardial infarction. This finding is
      in stark contrast to another recent study in which thymosin beta 4 treatment
      following myocardial infarction did not induce cardiomyocyte differentiation of
      EPDCs. While EPDCs seem to exhibit overall cardio-protective effects on the heart
      following myocardial infarction, they have not been shown to differentiate into
      cardiomyocytes in a clinically relevant setting. It will be important to
      understand why the ability of one therapeutic agent to induce cardiomyocyte
      differentiation of EPDCs seemingly depends on a single variable, i.e. the time of
      administration. Furthermore, in light of a recent report, it appears that
      thymosin beta 4 may be dispensable for cardiac development.

PMID- 22628112
TI  - Effect of small molecule supplements during in vitro culture of mouse zygotes and
      parthenogenetic embryos on hypoblast formation and stem cell derivation.
AB  - BACKGROUND: Small molecule inhibitors are organic components that modulate
      signalling pathways and have the ability to change the differentiation state of
      cells. They have been used to increase the efficiency of induced pluripotent stem
      cell generation and to support stem cell derivation and culture. In this study,
      we aimed to evaluate the effects of small molecules on the development of mouse
      zygotes and parthenogenetic embryos. METHODS AND RESULTS: Three inhibitors (SC-1,
      PD0325901 and BIO) were added to the culture medium from the 2-cell stage
      onwards. We have observed that addition of an inhibitor of the fibroblast growth
      factor (FGF) pathway (SC-1 or PD0325901) compromises the segregation of hypoblast
      from the inner cell mass (ICM). Given no difference was observed in size of the
      ICM, but more epiblast cells were found in these embryos, we can conclude that
      this is caused by redirection of all ICM cells to the epiblast. We also
      determined the consequences of reduced hypoblast and increased epiblast formation
      on stem cell derivation efficiency. No significant difference was found between
      derivation rates from treated embryos as compared to controls. However, only
      under 2i + ROCKi conditions, stem cells could be derived with an efficiency of
      more than 90%. Addition of BIO, an activator of the WNT pathway, did not have any
      effects on hypoblast development or stem cell derivation. CONCLUSION: We have
      demonstrated that FGF signalling is crucial for hypoblast generation and small
      molecules can be efficiently used to inhibit this process both in zygotes and
      parthenogenetic embryos.

PMID- 22628111
TI  - Lessons from the embryonic neural stem cell niche for neural lineage
      differentiation of pluripotent stem cells.
AB  - Pluripotent stem cells offer an abundant and malleable source for the generation
      of differentiated cells for transplantation as well as for in vitro screens.
      Patterning and differentiation protocols have been developed to generate neural
      progeny from human embryonic or induced pluripotent stem cells. However,
      continued refinement is required to enhance efficiency and to prevent the
      generation of unwanted cell types. We summarize and interpret insights gained
      from studies of embryonic neuroepithelium. A multitude of factors including
      soluble molecules, interactions with the extracellular matrix and neighboring
      cells cooperate to control neural stem cell self-renewal versus differentiation.
      Applying these findings and concepts to human stem cell systems in vitro may
      yield more appropriately patterned cell types for biomedical applications.

PMID- 22628115
TI  - Telerobotic manipulation of the brachial plexus.
AB  - OBJECTIVE: This study demonstrates the new technology of the robotic telesurgery
      on three brachial plexus reconstructions. We also discuss the implications,
      problems, and benefits of robotically assisted brachial plexus surgery. METHODS:
      After the first experimental experience in a cadaveric model, the authors
      performed three brachial plexus reconstructions. The surgery followed the
      traditional brachial plexus approach. From the moment that nervous sutures would
      be performed, the Da Vinci(r) (Intuitive SurgicalTM, Sunnyvale, CA) equipment was
      docked at the patients, positioned behind the patient's head, and the
      microsurgical steps were performed by using robotic telemanipulation. RESULTS:
      The first procedure was performed in a cadaver to gain experience and establish a
      surgical protocol by using the robot. In all the three living patients, the goals
      of the surgical procedure were achieved using the telerobotic manipulation.
      CONCLUSION: Robot-assisted surgery allows performance of high-dexterity surgical
      operations with the help of robotic arms and it improves the surgery due to
      tremor filtration, motion scaling, and ergonomics. The benefit of using the robot
      on microsurgery was reached, but its entire potential was not realized because
      the instruments used on those first experimental and clinical cases were not
      specifically designed for microsurgery.

PMID- 22628113
TI  - The evolving role of the aryl hydrocarbon receptor (AHR) in the normophysiology
      of hematopoiesis.
AB  - In addition to its role as a toxicological signal mediator, the Aryl Hydrocarbon
      Receptor (AHR) is also a transcription factor known to regulate cellular
      responses to oxidative stress and inflammation through transcriptional regulation
      of molecules involved in the signaling of nucear factor-erythroid 2-related
      factor-2 (Nrf2), p53 (TRP53), retinoblastoma (RB1), and NFkappaB. Recent research
      suggests that AHR activation of these signaling pathways may provide the
      molecular basis for understanding AHR's evolving role in endogenous developmental
      functions during hematopoietic stem-cell maintenance and differentiation. Recent
      developments into the hematopoietic roles for AHR are reviewed, aiming to
      reconcile divergent findings as to the endogenous function of AHR in
      hematopoiesis. Potential mechanistic explanations for AHR's involvement in
      hematopoietic differentiation are discussed, focusing on its known role as a cell
      cycle mediator and its interactions with Hypoxia-inducible transcription factor-1
      alpha (HIF1-alpha). Understanding the physiological mechanisms of AHR activation
      and signaling have far reaching implications ranging from explaining the action
      of various toxicological agents to providing novel ways to expand stem cell
      populations ex vivo for use in transplant therapies.

PMID- 22628114
TI  - Phenotypic and functional characterization of mesenchymal stem cells from
      chorionic villi of human term placenta.
AB  - BACKGROUND: Bone marrow derived mesenchymal stem cells (BM-MSCs) are used
      extensively in transplantation but their use is associated with many problems
      including low abundance in BM, low overall number, decreased differentiation
      potential with age and the invasive isolation procedures needed to obtain BM. We
      report a novel method of isolating placental MSCs (pMSCs) from chorionic villi,
      which exhibit the phenotypic and functional characteristics that will make them
      an attractive source of MSCs for cell-based therapy. METHODS: A novel explant
      approach was used to isolate pMSCs from chorionic villi of human placentae. These
      pMSCs were characterized by flow cytometry and were differentiated into
      adipocytes, osteocytes and chondrocytes using differentiation medium as
      demonstrated by cytochemical staining. The gene and protein expression profiles
      of pMSCs were also characterized using real time polymerase chain reaction (PCR)
      and flow cytometry, respectively. In addition, cytokine secretion by pMSCs was
      also analysed using sandwich enzyme-linked immunosorbent assay (ELISA) technique.
      Moreover, the migration and proliferation potentials of pMSCs were also
      determined. RESULTS: pMSCs were isolated from fetal part of the chorionic villi
      and these pMSCs expressed CD44, CD90, CD105, CD146, CD166 and HLA-ABC but not
      CD14, CD19, CD40, CD45, CD80, CD83, CD86 and HLA-DR. In addition, these pMSCs
      differentiated into osteocytes, chondrocytes and adipocytes and they also
      expressed several adhesion molecules, chemokines/receptors, growth factor
      receptors and cytokines/receptors. Moreover, they secreted many cytokines (IL
      1Ra, IL6, IL8, IL10, IL11 and IL15) and they were able to proliferate.
      Furthermore, they migrated in response to chemotactic factors including stromal
      cell-derived factor-1 (SDF-1), platelet derived growth factor (PDGF), hepatocyte
      growth factor (HGF), and monocyte chemotactic protein-1 (MCP-1). CONCLUSIONS: We
      devised a novel explant method of isolating pMSCs that expressed many biological
      factors responsible for mediating cellular processes such as migration/homing,
      immune modulation and angiogenesis. Therefore, we suggest that pMSCs prepared
      from human term placental chorionic villous explants are an attractive source of
      MSCs for cell therapy.

PMID- 22628116
TI  - A PY-nuclear localization signal is required for nuclear accumulation of HCMV
      UL79 protein.
AB  - Human cytomegalovirus UL79 protein is recently reported to be required for
      transcription or efficient accumulation of late viral mRNAs during viral
      infection. An absolute nuclear distribution of UL79 proteins has been observed
      with immunofluorescence assay, both during the infection of Flag-tagged UL79
      recombinant virus and in the HFFs expressing HA-tagged UL79, with or without
      virus infection. However, little is known about the nuclear import mechanism of
      UL79 protein. Here, by utilizing living cells fluorescent microscopy, a
      predominant nuclear localization of UL79 protein in living cells was detected.
      Furthermore, the nuclear import of UL79 protein was demonstrated to be dependent
      on the transportin-1-mediated pathway. Finally, a hydrophobic PY-nuclear
      localization signal (PY-NLS) was delineated between the amino acids 66-92 of UL79
      protein. Collectively, we provide evidence that a PY-NLS, firstly described in
      viral proteins, is responsible for the nuclear accumulation of UL79 protein.

PMID- 22628117
TI  - Optical fiber-based core-shell coaxially structured hybrid cells for self-powered
      nanosystems.
AB  - An optical fiber-based 3D hybrid cell consisting of a coaxially structured dye
      sensitized solar cell (DSSC) and a nanogenerator (NG) for simultaneously or
      independently harvesting solar and mechanical energy is demonstrated. The current
      output of the hybrid cell is dominated by the DSSC, and the voltage output is
      dominated by the NG; these can be utilized complementarily for different
      applications. The output of the hybrid cell is about 7.65 MUA current and 3.3 V
      voltage, which is strong enough to power nanodevices and even commercial
      electronic components.

PMID- 22628119
TI  - Cancer, concepts, cohorts and complexity: avoiding oversimplification of
      overdiagnosis.

PMID- 22628118
TI  - Allergic rhinitis and non-allergic rhinitis in children in the tropics:
      prevalence and risk associations.
AB  - BACKGROUND: The age-related comparative prevalence of allergic rhinitis (AR) and
      non-allergic rhinitis (NAR) in children is poorly defined. We aimed to
      characterize AR and NAR in children. METHODS: This study enrolled children with
      chronic rhinitis who presented to a tertiary paediatric center for a diagnostic
      skin prick test (SPT). Parents completed a medical history questionnaire for
      their child, including disease activity for asthma and rhinitis. Sociodemographic
      data was obtained and all participants underwent a common inhalant SPT panel. A
      positive SPT indicated AR. RESULTS: From March 2001 to March 2009, 6,660 children
      (64% male) were enrolled (aged 6 months to 19 years, mean 7.82 years). Only 3.7%
      (249) of the children were <2 years old, and almost 30% of these had AR. Most
      children with AR (73%) presented after age 6. Males were more likely to have AR
      (vs. NAR) (OR 1.5; CI 1.39-1.77). Antihistamine and salbutamol use did not differ
      between children with AR and NAR. Children with AR were more likely to require
      adjunct therapy with inhaled corticosteroids (51.2% vs. 43.2%, P < 0.001), have
      drug hypersensitivity (especially antipyretic drugs) (2.5% vs. 1.3%, P = 0.384)
      or an asthma admission (9.1% vs. 6.0%, P < 0.001). CONCLUSIONS: AR is more common
      in male children, is relatively rare below the age of 2 years, and accounts for
      two-thirds of all childhood chronic rhinitis and 73.3% of all chronic rhinitis in
      school-aged children (>=6 years old). Children with AR have more severe rhinitis
      symptoms and more often suffer from asthma-related events and admissions.

PMID- 22628120
TI  - Randomised controlled trial of amoxycillin clavulanate in children with chronic
      wet cough.
AB  - BACKGROUND: Despite guideline recommendations, there are no published randomised
      controlled trial data on the efficacy of antibiotics for chronic wet cough in
      children. The majority of children with chronic wet cough have protracted
      bacterial bronchitis (PBB), a recognised condition in multiple national
      guidelines. The authors conducted a parallel 1:1 placebo randomised controlled
      trial to test the hypothesis that a 2-week course of amoxycillin clavulanate is
      efficacious in the treatment of children with chronic wet cough. METHODS: 50
      children (median age 1.9 years, IQR 0.9-5.1) with chronic (>3 weeks) wet cough
      were randomised to 2 weeks of twice daily oral amoxycillin clavulanate (22.5
      mg/kg/dose) or placebo. The primary outcome was 'cough resolution' defined as a
      >75% reduction in the validated verbal category descriptive cough score within 14
      days of treatment compared with baseline scores, or cessation of cough for >3
      days. In selected children, flexible bronchoscopy and bronchoalveolar lavage
      (BAL) were undertaken at baseline. RESULTS: Cough resolution rates (48%) were
      significantly higher in children who received amoxycillin clavulanate compared
      with those who received placebo (16%), p=0.016. The observed difference between
      proportions was 0.32 (95% CI 0.08 to 0.56). Post treatment, median verbal
      category descriptive score in the amoxycillin clavulanate group of 0.5 (IQR 0.0
      2.0) was significantly lower than in the placebo group, 2.25 (IQR 1.15-2.9)
      (p=0.02). Pre-treatment BAL data were consistent with PBB in the majority of
      children, with no significant difference between groups. CONCLUSION: A 2-week
      course of amoxycillin clavulanate will achieve cough resolution in a significant
      number of children with chronic wet cough. BAL data support the diagnosis of PBB
      in the majority of these children. CLINICAL TRIAL NUMBER: ACTRN 12605000533695.

PMID- 22628121
TI  - Production of leukotriene B4 by Paracoccidioides brasiliensis.
AB  - Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most
      prevalent deep mycosis in Latin America. The production of eicosanoids during
      fungal infection has been associated with the biology of these microorganisms and
      modulation of host immune response. The aim of our study was to evaluate whether
      P. brasiliensis strains with high or low virulence produce leukotriene B4 (LTB4),
      using endogenous and/or exogenous sources of arachidonic acid (AA). Moreover, we
      assessed whether this fungus might use the same metabolic pathway, described for
      mammalian cells, that involves the lipoxygenase (LOX) enzyme. The association
      between the production of this eicosanoid and fungus survival and growth was also
      evaluated. Our results showed that P. brasiliensis, irrespective of its
      virulence, produces high levels of LTB4 using endogenous AA. In addition, in
      cultures treated with exogenous AA, LTB4 levels were significantly higher,
      showing that this fungus also uses exogenous sources of fatty acids. Treatment
      with MK886, which blocks the activity of lipoxygenase, by inhibiting five
      lipoxygenase-activating protein (FLAP) or with nordihydroguaiaretic acid (NDGA),
      a non-selective lipoxygenase inhibitor, resulted in a significant reduction in
      LTB4 levels, indicating that the fungus produces this eicosanoid by using the LOX
      pathway or an enzyme with biochemically similar function. The significant
      reduction in viability detected in cultures treated with these inhibitors was,
      however, restored by adding exogenous LTB4 , confirming the role of this
      eicosanoid in fungus survival. Moreover, the addition of LTB4 to cultures capable
      of producing LTs induces fungal growth. These results provide a foundation for
      additional studies on the contributions of LTB4 in P. brasiliensis virulence.

PMID- 22628124
TI  - Molecular dynamics simulation of atomic-scale frictional behavior of corrugated
      nano-structured surfaces.
AB  - Surface morphology is one of the critical parameters that affect the frictional
      behavior of two contacting bodies in relative motion. It is important because the
      real contact area as well as the contact stiffness is dictated by the micro- and
      nano-scale geometry of the surface. In this regard, the frictional behavior may
      be controlled by varying the surface morphology through nano-structuring. In this
      study, molecular dynamics simulations were conducted to investigate the effects
      of contact area and structural stiffness of corrugated nano-structures on the
      fundamental frictional behavior at the atomic-scale. The nano-structured surface
      was modeled as an array of corrugated carbon atoms with a given periodicity. It
      was found that the friction coefficient of the nano-structured surface was lower
      than that of a smooth surface under specific contact conditions. The effect of
      applied load on the friction coefficient was dependent on the size of the
      corrugation. Furthermore, stiffness of the nano-structure was identified to be an
      important variable in dictating the frictional behavior.

PMID- 22628122
TI  - On lateral septum-like characteristics of outputs from the accumbal hedonic
      "hotspot" of Pecina and Berridge with commentary on the transitional nature of
      basal forebrain "boundaries".
AB  - Pecina and Berridge (2005; J Neurosci 25:11777-11786) observed that an injection
      of the MU-opioid receptor agonist DAMGO (D-ala(2) -N-Me-Phe(4) -Glycol(5) 
      enkephalin) into the rostrodorsal part of the accumbens shell (rdAcbSh) enhances
      expression of hedonic "liking" responses to the taste of an appetitive sucrose
      solution. Insofar as the connections of this hedonic "hotspot" were not singled
      out for special attention in the earlier neuroanatomical literature, we undertook
      to examine them. We observed that the patterns of inputs and outputs of the
      rdAcbSh are not qualitatively different from those of the rest of the Acb, except
      that outputs from the rdAcbSh to the lateral preoptic area and anterior and
      lateral hypothalamic areas are anomalously robust and overlap extensively with
      those of the lateral septum. We also detected reciprocal interconnections between
      the rdAcbSh and lateral septum. Whether and how these connections subserve
      hedonic impact remains to be learned, but these observations lead us to
      hypothesize that the rdAcbSh represents a basal forebrain transition area, in the
      sense that it is invaded by neurons of the lateral septum, or possibly
      transitional neuronal forms sharing properties of both structures. We note that
      the proposed transition zone between lateral septum and rdAcbSh would be but one
      of many in the basal forebrain and conclude by reiterating the longstanding
      argument that the transitional nature of such boundary areas has functional
      importance, of which the precise nature will remain elusive until the
      neurophysiological and neuropharmacological implications of such zones of
      transition are more generally acknowledged and better addressed.

PMID- 22628123
TI  - High-throughput analysis of tumor necrosis factor signaling pathways in eight
      cell types during rat hepatic regeneration.
AB  - This study aims to clarify the relevance of tumor necrosis factor (TNFs)
      signaling pathways and liver regeneration (LR) at the cellular level. Eight liver
      cell types were isolated using Percoll density gradient centrifugation and
      immunomagnetic beads methods. Expressions of TNF signaling pathway-involved genes
      in each cell type after 2/3 hepatectomy (PH) were detected using gene chip.
      Results show the following: gene TNFalpha was upregulated in most cell types,
      especially in Kupffer cells (KC); TNFbeta expression was insignificantly changed
      in eight liver cell types; the majority of genes involved in four TNFalpha
      signaling pathways showed increased expression during LR in hepatocytes (HC);
      TNFalpha-induced NFkappaB pathway-involved genes were upregulated preferentially
      between 2 and 24 h during LR in biliary epithelial cells (BECs); and TNFalpha
      induced apoptotic pathway genes were downregulated preferentially at progressing
      phase of LR in dendritic cells (DCs). Referring to the above results, TNFalpha
      mediated signaling pathways, in contrast to TNFbeta, play the more proactive role
      in LR, and four TNFalpha-mediated signaling pathways seem helpful to regulate
      biological events in HC; BEC proliferation was partly controlled by TNFalpha
      mediated NFkappaB pathway; and the impaired TNFalpha-mediated apoptotic pathway
      in DCs might contribute to the restoration of DC mass after PH. Briefly, the
      comparative analysis of genomewide expression profiles of TNF signaling pathways
      between different cell types is helpful in understanding the implication of TNF
      signaling in LR at the cellular level.

PMID- 22628125
TI  - Neurocircuitry of generalized anxiety disorder in adolescents: a pilot functional
      neuroimaging and functional connectivity study.
AB  - BACKGROUND: Dysfunction of neural systems responsible for the processing of
      emotional stimuli is hypothesized to be involved in the pathophysiology of
      generalized anxiety disorder (GAD) in adolescents. We used standard fMRI and
      functional connectivity analyses to examine the functional neurocircuitry of GAD
      in adolescents. METHODS: Ten adolescents with GAD and 10 healthy comparison
      subjects underwent fMRI while performing a continuous performance task with
      emotional and neutral distractors. Standard event-related voxel-wise fMRI and
      steady-state functional connectivity analyses were performed. RESULTS: Increased
      activation was observed in the left medial prefrontal cortex and right
      ventrolateral prefrontal cortex (VLPFC) in response to emotional images compared
      to neutral imagines in youth with GAD. Connectivity analyses using the right
      VLPFC seed region suggested decreased connectivity between this region and the
      bilateral medial prefrontal cortex. Connectivity analyses using the right
      amygdala seed region revealed decreased correlation with the posterior cingulate
      cortex in adolescents with GAD. The left amygdala seed region demonstrated
      increased connectivity with the ipsilateral precuneus in youth with GAD compared
      to healthy subjects. CONCLUSIONS: In addition to increased activation of the
      medial prefrontal cortex and right VLPFC, we observed altered connectivity
      between the amygdala or VLPFC and regions, which subserve mentalization (e.g.
      posterior cingulate cortex, precuneus, and medial prefrontal cortex). This
      suggests that structures that regulate emotion and affect interact abnormally
      with key structures that are involved in mentalization, a process known to be
      disrupted in GAD.

PMID- 22628126
TI  - Measuring quantities using oscillators and pulse generators.
AB  - This article presents properties of the clock-counter model with a periodic
      generator employed as the source of regularly emitted pulses. The pacemaker and
      accumulator mechanisms are often considered in research in neurobiology and
      cognitive science: neurons or their groups serve as oscillators, and the number
      of spikes emitted while a stimulus lasts becomes an estimate of the length of the
      stimulus. The article integrates three approaches: a theoretical model to present
      the general concept, a working implementation of this model to perform intensive
      simulation experiments, and the analytical description of the behavior of the
      model. Oscillators that exhibit some degree of regularity have been compared to
      the Poisson ones, and the corresponding probability distributions have been
      presented that describe the number of pulses accumulated over time. Several
      continuous and discrete interpulse distributions have been investigated, and the
      influence of generator parameters on the possible outcomes of the measurement
      have been described. Particular attention has been paid to the relationship
      between measurement variability and the mean number of pulses observed. Issues
      concerning practical realizations of periodic generators: discrete time,
      dependence of the generator start time on the stimulus, and relation to Weber's
      law have been discussed as well.

PMID- 22628127
TI  - Transformative research: definitions, approaches and consequences.
AB  - In this perspective a definition of transformative research (TR) is proposed and
      discussed. We define TR as that which "transforms" or causes a major change in
      thought patterns concerning an area of scientific endeavor. This type of research
      is often elusive, requires different approaches and sometimes depends on a bit of
      luck. TR concerns intangibles such as human intuition, serendipity, unpredictable
      events, implausible hypotheses, a well-prepared mind and often interpersonal
      communications. Examples are provided to illustrate how TR may unfold.
      Contributions it makes to basic and applied humanistic knowledge are highlighted.

PMID- 22628129
TI  - [2012 Health Care Structural Regulation - what is really changing?].

PMID- 22628130
TI  - Genetic heterogeneity according to age at onset in bipolar disorder: a combined
      positional cloning and candidate gene approach.
AB  - This study is the first that formally tests for genetic heterogeneity of bipolar
      disorder (BD) according to age at onset (AAO) sub-groups by combining positional
      cloning and candidate gene approaches. Our previous genome-wide linkage-scan
      identified five genomic regions linked to early-onset form of BD. The present
      study uses association analysis to test genetic heterogeneity of candidate genes
      located in these five regions in a sample of 443 unrelated bipolar patients and
      1,731 controls. The study involved the following steps: (1) test of heterogeneity
      by comparing early-onset BD patients versus later-onset BD patients; and (2) for
      significant results in step 1, comparison of early-onset BD patients and later
      onset BD patients separately to controls. Two types of analyses were used: the
      single SNP test and the gene-based association test. We provide evidence for
      genetic heterogeneity within the ADRB2 (beta-2adrenoreceptor) gene region that is
      specifically associated with the early onset form of BD with an OR of 1.8.
      Unfortunately, the genotyping coverage of ADRB2 in the Wellcome Trust Case
      Control Consortium sample meant undermined our efforts to undertake a
      replication. However, as the ADRB2 gene product directly interacts with the
      CACNA1C gene product, and is known to be implicated in BD susceptibility, we
      conclude that further exploration of the relationships between ADRB2 and BD needs
      to be undertaken.

PMID- 22628131
TI  - Comparing risk prediction models.

PMID- 22628132
TI  - Screen all baby boomers for hepatitis C, advises US public health agency.

PMID- 22628133
TI  - Experts call for greater transparency on safety of implants.

PMID- 22628134
TI  - Doctor who helped locate bin Laden family is sentenced to 33 years in jail.

PMID- 22628135
TI  - GPs must not be left out of clinical commissioning, warns BMA.

PMID- 22628136
TI  - The use of a consultant-led ward round checklist to improve paediatric
      prescribing: an interrupted time series study.
AB  - A Check and Correct checklist has previously been developed to increase feedback
      on prescribing quality and enhance physicians' focus on patients' drug charts
      during ward rounds. Our objective was to assess the impact of introducing such a
      prescribing checklist on the quality and safety of inpatient prescribing in two
      paediatric wards in a London teaching hospital. Between 15 March 2011 and 15 May
      2011 (pre-intervention) and between 23 May 2011 and 23 July 2011 (post
      intervention), we recorded rates of both technical prescription writing errors
      and clinical prescribing errors twice a week. During the pre-intervention period,
      the overall technical error rate was 10.8 % (95 % confidence interval 10.3 %-11.2
      %); the clinical error rate was 4.7 % (3.4 %-6.6 %). The most common errors were
      absence of prescriber's contact details and dose omissions. After the
      implementation of Check and Correct, error rates were 7.3 % (6.9 %-7.8 %) and 5.5
      % (3.9 %-7.9 %), respectively. Segmented regression analysis revealed a
      significant decrease of -5.0 % in the technical error rate (-7.1 to -2.9 %; -37.7
      % relative decrease; R (2) = 0.604) following the intervention, independent of
      changes in overall medical records' documentation quality. Regarding clinical
      errors, no significant impact of the intervention could be detected. CONCLUSION:
      Implementing a Check and Correct checklist led to an improvement in the quality
      of prescription writing. Although a change in culture may be needed to maximise
      its potential, we would recommend its more widespread use and evaluation.

PMID- 22628137
TI  - Targeted fluconazole prophylaxis for high-risk very low birth weight infants.
AB  - Antifungal prophylaxis is increasingly used in very low birth weight (VLBW)
      infants who are at risk for severe fungal infections. Our objective was to assess
      the effectiveness of targeted fluconazole prophylaxis for high-risk VLBW infants.
      A retrospective cohort study with historical controls was performed. During the
      period 2007-2008, all high-risk VLBW infants (birth weight, <=1,000 g;
      gestational age, <=28 weeks; seven antimicrobial therapy or additional risk
      factors present) received fluconazole prophylaxis until risk factors were not
      present. Treated infants were compared to a gestational age- and birth weight
      matched untreated cohort. Statistical analyses used univariate and multivariate
      analyses. The main outcome variable was a breakthrough fungal bloodstream
      infection (BSI). The prophylaxis cohort of 130 VLBW infants was compared to 319
      control infants. The rate of fungal infections was significantly lower in the
      fluconazole prophylaxis group (1 of 130 vs. 19 of 319, p = 0.016); however, they
      did not differ in mortality (16.2 vs. 15 %, p = 0.77) or complications of
      prematurity. Fluconazole prophylaxis was associated with a significant decrease
      in candidal BSI (odds ratio, 0.05; 95 % confidence interval, 0.005-0.523).
      Selective vs. nonselective prophylaxis reduced the number of infants treated from
      247 to 130. Conclusion Targeted fluconazole prophylaxis in VLBW infants is
      effective in preventing fungal infections without increasing the risk of BSI
      among low-risk infants.

PMID- 22628138
TI  - Theoretical approach towards the understanding of asymmetric additions of
      dialkylzinc to enals and iminals catalysed by [2.2]paracyclophane-based N,O
      ligands.
AB  - The 1,2- and 1,4-asymmetric additions of dialkylzinc reagents (ZnMe(2) and
      ZnEt(2)) to cinnamaldehyde and N-formylbenzylimine catalysed by
      [2.2]paracyclophane-based N,O-ligands were studied with quantum chemical methods.
      High level LPNO-CEPA/1 (local pair natural orbital coupled electron pair
      approximation 1) calculations were performed to obtain reliable reaction barriers
      and binding energies. The calculations supported the experimentally observed
      selectivities. In the reaction, the alkyl transfer takes place on a binuclear
      zinc complex. Regioselectivity can be traced back to changes in pi-conjugation.
      Because the less conjugated N-formylbenzylimine is more flexible, it is better
      suited for 1,4-additions. Moreover, bulky ligands were shown to be important for
      stereoselectivity. The reason is that the tricyclic motif present in the
      transition states is sterically less hindered in the anti conformation. Based on
      the LPNO-CEPA/1 data, a set of popular theoretical methods are validated.
      Although it was possible to set up a procedure to obtain the stereoselectivities
      with computationally less demanding methods, this was not possible for the
      regioselectivity of the reactions.

PMID- 22628139
TI  - Parent-of-origin effects in ADHD: distinct influences of paternal and maternal
      ADHD on neuropsychological functioning in offspring.
AB  - OBJECTIVE: The authors examined parent-of-origin effects in transmission of ADHD
      and neuropsychological functioning. Proof of these effects can identify more
      etiologically homogeneous ADHD subgroups and facilitate genetic studies. METHOD:
      The authors included 238 ADHD and 147 control families. ADHD in children was
      assessed using parent and teacher ratings, while parents completed self-reports.
      Children were assessed with neuropsychological paradigms measuring IQ, motor,
      timing, and executive functions. RESULTS: Paternal and maternal ADHD were equally
      positively related to ADHD in offspring. Paternal ADHD was related to poorer time
      reproduction in offspring and to lower verbal and total IQ in daughters. Maternal
      ADHD was related to poorer inhibition and motor control in offspring. No
      mediating effects of neuropsychological functions were found between parent and
      offspring ADHD symptoms. CONCLUSION: Neuropsychological functions may be more
      sensitive to parent-of-origin effects than ADHD symptoms and possibly useful in
      detecting the transmission of different gene-brain network pathways depending on
      parental sex.

PMID- 22628140
TI  - Cognitive behavioral treatment outcomes in adolescent ADHD.
AB  - OBJECTIVE: To assess the efficacy of cognitive behavioral therapy (CBT) for
      managing adolescent ADHD. METHOD: A total of 68 adolescents with ADHD and
      associated psychiatric comorbidities completed a manualized CBT treatment
      protocol. The intervention used in the study was a downward extension of the
      Safren et al. program for adults with ADHD who have symptoms unresolved by
      medication. Outcome variables consisted of narrow band (ADHD) and broadband
      (e.g., mood, anxiety, conduct) symptom measures (Behavior Assessment System for
      Children-2nd edition and ADHD-Rating Scales) as well as functioning measures
      (parent/teacher ratings and several ecologically real-world measures). RESULTS:
      Treatment effects emerged on the medication dosage, parent rating of
      pharmacotherapy adherence, adolescent self-report of personal adjustment (e.g.,
      self-esteem), parent and teacher ratings of inattentive symptoms, school
      attendance, school tardiness, parent report of peer, family and academic
      functioning and teacher report of adolescent relationship with teacher, academic
      progress, and adolescent self-esteem. Adolescents with ADHD with oppositional
      defiant disorder were rated by parents and teachers as benefiting less from the
      CBT intervention. Adolescents with ADHD and comorbid anxiety/depression were
      rated by parents and teachers as benefiting more from the CBT intervention.
      CONCLUSION: A downward extension of an empirically validated adult ADHD CBT
      protocol can benefit some adolescents with ADHD.

PMID- 22628141
TI  - Child impairment and parenting self-efficacy in relation to mothers' views of
      ADHD treatments.
AB  - OBJECTIVE: This study assessed the relations of child impairment and parenting
      self-efficacy with parental views of the acceptability and effectiveness of
      behavioral, medication, and combined treatments for child ADHD. Child impairment
      and parenting self-efficacy were also assessed in relation to the effectiveness
      views of specific behavioral treatment strategies. METHOD: Ninety-five mothers of
      children with ADHD completed questionnaires assessing child impairment, parenting
      self-efficacy, perceptions of the overall acceptability and effectiveness of ADHD
      treatments, and views of the effectiveness of specific behavioral treatment
      strategies. RESULTS: Hierarchical linear modeling using child impairment and
      parenting self-efficacy as predictors of treatment views suggests that mothers
      viewed combined treatments as most acceptable and effective when their child was
      more impaired, and mothers with higher parenting self-efficacy rated behavioral
      treatment strategies as more effective. CONCLUSION: Child impairment and
      parenting self-efficacy are related to perceptions of the acceptability and/or
      effectiveness of ADHD treatments.

PMID- 22628142
TI  - Methylphenidate in children with ADHD with or without learning disability.
AB  - OBJECTIVE: To explore treatment response to Osmotic Release Oral System((r))
      (OROS) methylphenidate in children with ADHD with and without comorbid learning
      disability (LD). METHOD: Data were analyzed from two 6-week, double-blind,
      randomized, placebo-controlled, crossover studies evaluating individually
      determined doses of OROS methylphenidate versus placebo in 135 children (ages 9
      to 12 years) with ADHD with or without an LD in reading, math, or both. The
      sample was demographically diverse, with 31% females and more than 40% minority,
      predominantly African American and Hispanic. On two laboratory school days,
      participants received either OROS methylphenidate or placebo and were given a
      battery of cognitive and behavioral tests. RESULTS: Treatment with OROS
      methylphenidate led to improvement in ADHD Rating Scale scores for participants
      with or without comorbid LD. Both groups performed better during treatment with
      OROS methylphenidate than placebo on measures of cognitive skills (i.e., Test of
      Variables of Attention, Finger Windows Backwards), academically related tasks
      (i.e., Dynamic Indicators of Basic Early Literacy Skills, Test of Handwriting
      Skills-Revised, Permanent Product Math Test), and observed classroom behavior
      (i.e., Swanson, Kotkin, Alger, M-Flynn, and Pelham Scale). CONCLUSION: In
      children with ADHD with or without comorbid LD, behavior and performance improved
      during treatment with OROS methylphenidate.

PMID- 22628143
TI  - Video game performances are preserved in ADHD children compared with controls.
AB  - OBJECTIVE: Although ADHD and excessive video game playing have received some
      attention, few studies have explored the performances of ADHD children when
      playing video games. The authors hypothesized that performances of ADHD children
      would be as good as those of control children in motivating video games tasks but
      not in the Continuous Performance Test II (CPT II). METHOD: The sample consisted
      of 26 ADHD children and 16 control children. Performances of ADHD and control
      children were compared on three commercially available games, on the repetition
      of every game, and on the CPT II. RESULTS: ADHD children had lower performances
      on the CPT II than did controls, but they exhibited equivalent performances to
      controls when playing video games at both sessions and on all three games.
      CONCLUSION: When playing video games, ADHD children present no difference in
      inhibitory performances compared with control children. This demonstrates that
      cognitive difficulties in ADHD are task dependent.

PMID- 22628144
TI  - Viewing the viewers: how adults with attentional deficits watch educational
      videos.
AB  - OBJECTIVE: Knowing how adults with ADHD interact with prerecorded video lessons
      at home may provide a novel means of early screening and long-term monitoring for
      ADHD. METHOD: Viewing patterns of 484 students with known ADHD were compared with
      484 age, gender, and academically matched controls chosen from 8,699 non-ADHD
      students. Transcripts generated by their video playback software were analyzed
      using t tests and regression analysis. RESULTS: ADHD students displayed
      significant tendencies (p <= .05) to watch videos with more pauses and more
      reviews of previously watched parts. Other parameters showed similar tendencies.
      Regression analysis indicated that attentional deficits remained constant for age
      and gender but varied for learning experience. CONCLUSION: There were measurable
      and significant differences between the video-viewing habits of the ADHD and non
      ADHD students. This provides a new perspective on how adults cope with attention
      deficits and suggests a novel means of early screening for ADHD.

PMID- 22628145
TI  - Is the diagnosis of ADHD influenced by time of entry to school? An examination of
      clinical, familial, and functional correlates in children at early and late entry
      points.
AB  - OBJECTIVE: The authors examined the proposed immaturity hypothesis, which
      suggests that younger children may have developmental immaturity and not ADHD,
      using data from a large, clinically referred population of individuals with and
      without ADHD. METHOD: The sample consisted of individuals with and without an
      ADHD diagnosis, ascertained from ongoing studies in our laboratory, born in
      August (Younger Cohort N = 562) and born in September (Older Cohort N = 529). The
      authors compared studywide diagnosis rates of ADHD, ADHD familiality patterns,
      ADHD symptoms, psychiatric comorbidity, and functional impairments between the
      two cohorts. RESULTS: Studywide rates of ADHD diagnosis, ADHD-associated
      symptoms, ADHD-associated impairments, ADHD-associated comorbid disorders, and
      familiality were similar in the two age cohorts. CONCLUSION: Results showed that
      ADHD-associated familial, clinical, and functional correlates are similar
      irrespective of age at entry to school, indicating that when ADHD symptoms are
      present, a diagnosis of ADHD should be considered rather than attributing these
      symptoms to developmental immaturity.

PMID- 22628146
TI  - No link between date of birth and ADHD symptoms in adults.
AB  - OBJECTIVE: Research has highlighted several negative consequences for individuals
      born in the later part of the academic year, including increased likelihood of
      being diagnosed with learning disabilities. In this study, we considered whether
      birthdate predicted ADHD symptomatology using two well known mechanisms, the
      relative age effect (RAE) and the season of birth effect (SOBE). METHODS: Study
      participants completed two ADHD measures: Conners Adult ADHD Rating Scales
      (CAARS) and the Wender Utah Rating Scale (WURS). RESULTS: There were gender
      effects in the WURS data indicating that males scored higher than females on ADHD
      symptoms as well as a significant interaction in the CAARS data to support
      differential patterns among males and females. CONCLUSION: Overall, results did
      not support a RAE or SOBE among males or females. Possible reasons for these
      findings and their implications are discussed.

PMID- 22628147
TI  - Screening for working memory deficits in the classroom: the psychometric
      properties of the working memory rating scale in a longitudinal school-based
      study.
AB  - OBJECTIVE: The aim of this 18-month longitudinal study was to explore the
      psychometric properties of the recently developed Working Memory Rating Scale
      (WMRS) within a general school population of 524 six- to nine-year-old children
      (259 boys, 265 girls) and with an examination of sex and time differences.
      METHOD: Teachers completed the WMRS and children completed objective measures of
      WM and standardized measures of academic achievement. RESULTS: Confirmatory
      factor analyses indicated a poor fit for the 20 original WMRS items. Post hoc
      analyses, however, revealed that the factor structure of an alternative five-item
      short form was strong for both boys and girls and at the two time points,
      spanning two consecutive academic years. Internal consistency, criterion-related
      validity, and convergent validity of this alternative five-item WMRS were also
      excellent. CONCLUSION: The short five-item WMRS may eventually provide teachers
      with a useful and time-effective method to screen for WM deficits at school.

PMID- 22628148
TI  - ADHD prevalence in Lebanese school-age population.
AB  - OBJECTIVE: The authors conducted an epidemiological study in Lebanon to estimate
      ADHD prevalence in school-age population. METHOD: They selected 1,000 children
      aged between 6 and 10 years, admitted in several schools in Lebanon. In each
      district, they randomly chose five schools, and in each school two classes. From
      each class, 10 children were included randomly in the population of the study.
      For each child, an ADHD-Rating Scale-IV School version was filled by a main
      teacher. The Home version was filled by the child's parents. RESULTS: The
      prevalence of ADHD Inattentive subtype was 3 per 1,000, Hyperactive-Impulsive
      subtype 12 per 1,000, and ADHD Combined subtype 17 per 1,000. ADHD was
      significantly more prevalent in boys than in girls. CONCLUSION: This is the first
      epidemiological study to be conducted in Lebanon to estimate the prevalence of
      ADHD among children.

PMID- 22628149
TI  - Dysfunctional cognitions and their emotional, behavioral, and functional
      correlates in adults with attention deficit hyperactivity disorder (ADHD): is the
      cognitive-behavioral model valid?
AB  - OBJECTIVE: To investigate the presence of dysfunctional cognitions in adults with
      ADHD and to determine whether these cognitions are associated with emotional
      symptoms, maladaptive coping, and functional impairment, as predicted by the
      cognitive-behavioral model. METHOD: A total of 35 adult participants with ADHD,
      20 nonclinical controls, and 20 non-ADHD clinical controls were assessed with
      measures of ADHD symptoms, dysfunctional cognitions, depression and anxiety
      symptoms, coping strategies, and quality of life. RESULTS: ADHD group showed
      elevated scores of dysfunctional cognitions relative to nonclinical control group
      and comparable with clinical control group. Dysfunctional cognitions were
      strongly associated with emotional symptoms. ADHD group also showed elevated
      scores in maladaptive coping strategies of the escape-avoidance type. Life
      impairment was satisfactorily predicted in data analysis when ADHD symptoms,
      dysfunctional cognitions, and emotional symptoms were fitted into a regression
      model. CONCLUSION: Cognitive-behavioral therapy model appears to be a valid
      complementary model for understanding emotional and life impairment in adults
      with ADHD.

PMID- 22628150
TI  - Variants at chromosome 20 (ASIP locus) and melanoma risk.
AB  - Agouti signaling protein (ASIP) locus on chromosome 20q11 is implicated, as shown
      by genome-wide association studies, in phenotype variation and melanoma risk. We
      genotyped 837 melanoma cases and 1,154 controls for 21 single nucleotide
      polymorphisms (SNPs) informative for 495 polymorphisms at the locus. Our data
      showed an increased risk of melanoma (odds ratio [OR] 1.27, 95% confidence
      interval [95% CI] 1.03-1.57) in carriers of the rs4911414 variant, located 120 kb
      upstream of ASIP. The main effect of rs4911414, as reported previously, was in
      tandem with a 10 kb adjacent polymorphism rs1015362; two constituted risk
      associated haplotype/diplotype. Except for rs1015363, none of the 12 tagging
      SNPs, genotyped to cover 239.9 kb region with polymorphisms linked to rs4911414
      and rs1015362, were associated with melanoma. Our data confirmed a previous
      association of melanoma risk (OR 1.82, 95% CI 1.37-2.41) with rs4911442, located
      in intron 5 of the nuclear receptor coactivator 6 (NCOA6) gene. The rs910871, one
      of the six variants, genotyped to cover NCOA6, showed an association with
      melanoma risk (OR 1.33, 95% CI 1.04-1.70). Both, rs4911442 and rs910871 were in
      moderate linkage with a, previously reported, risk-associated rs910873
      polymorphism. A haplotype from the variants within NCOA6 showed an association
      with risk of melanoma (OR 1.49, 95% CI 1.17-1.88). Interaction between risk
      associated polymorphisms and previously genotyped melanocortin receptor 1 (MC1R)
      variants, in our study, was not statistically significant. Nevertheless, the
      carriers of the variant alleles over the background of MC1R variants were at a
      higher risk than the carriers not enriched for MC1R variants. Our data confirmed
      the association of different variants at chromosome 20q11 with melanoma risk.

PMID- 22628152
TI  - Low vegetable intake is associated with allergic asthma and moderate-to-severe
      airway hyperresponsiveness.
AB  - BACKGROUND: In recent decades, children's diet quality has changed and asthma
      prevalence has increased, although it remains unclear if these events are
      associated. OBJECTIVE: To examine children's total and component diet quality and
      asthma and airway hyperresponsiveness (AHR), a proxy for asthma severity.
      METHODS: Food frequency questionnaires adapted from the Nurses' Health Study and
      supplemented with foods whose nutrients which have garnered interest of late in
      relation to asthma were administered. From these data, diet quality scores (total
      and component), based on the Youth Healthy Eating Index (YHEI adapted) were
      developed. Asthma assessments were performed by pediatric allergists and
      classified by atopic status: Allergic asthma (>=1 positive skin prick test to
      common allergens >3 mm compared to negative control) versus non-allergic asthma
      (negative skin prick test). AHR was assessed via the Cockcroft technique.
      Participants included 270 boys (30% with asthma) and 206 girls (33% with asthma)
      involved in the 1995 Manitoba Prospective Cohort Study nested case-control study.
      Logistic regression was used to examine associations between diet quality and
      asthma, and multinomial logistic regression was used to examine associations
      between diet quality and AHR. RESULTS: Four hundred seventy six children (56.7%
      boys) were seen at 12.6 +/- 0.5 years. Asthma and AHR prevalence were 26.2 and
      53.8%, respectively. In fully adjusted models, high vegetable intake was
      protective against allergic asthma (OR 0.49; 95% CI 0.29-0.84; P < 0.009) and
      moderate/severe AHR (OR 0.58; 0.37-0.91; P < 0.019). CONCLUSIONS: Vegetable
      intake is inversely associated with allergic asthma and moderate/severe AHR.

PMID- 22628151
TI  - Keeping children safe at home: protocol for three matched case-control studies of
      modifiable risk factors for falls.
AB  - BACKGROUND: Childhood falls result in considerable morbidity, mortality and
      health service use. Despite this, little evidence exists on protective factors or
      effective falls prevention interventions in young children. OBJECTIVES: To
      estimate ORs for three types of medically attended fall injuries in young
      children in relation to safety equipment, safety behaviours and hazard reduction
      and explore differential effects by child and family factors and injury severity.
      DESIGN: Three multicentre case-control studies in UK hospitals with validation of
      parental reported exposures using home observations. Cases are aged 0-4 years
      with a medically attended fall injury occurring at home, matched on age and sex
      with community controls. Children attending hospital for other types of injury
      will serve as unmatched hospital controls. Matched analyses will use conditional
      logistic regression to adjust for potential confounding variables. Unmatched
      analyses will use unconditional logistic regression, adjusted for age, sex,
      deprivation and distance from hospital in addition to other confounders. Each
      study requires 496 cases and 1984 controls to detect an OR of 0.7, with 80%
      power, 5% significance level, a correlation between cases and controls of 0.1 and
      a range of exposure prevalences. MAIN OUTCOME MEASURES: Falls on stairs, on one
      level and from furniture. DISCUSSION: As the largest in the field to date, these
      case control studies will adjust for potential confounders, validate measures of
      exposure and investigate modifiable risk factors for specific falls injury
      mechanisms. Findings should enhance the evidence base for falls prevention for
      young children.

PMID- 22628153
TI  - Superior labrum anterior and posterior lesions of the shoulder: incidence rates,
      complications, and outcomes as reported by American Board of Orthopedic Surgery.
      Part II candidates.
AB  - BACKGROUND: Tears of the superior labrum (superior labrum anterior and posterior
      [SLAP] lesions) of the shoulder are uncommon injuries; however, the incidence of
      surgical correction seems to be increasing. PURPOSE: To report the findings of a
      review of a proprietary descriptive database that catalogs cases for the purpose
      of board certification on the demographics of SLAP lesion repair. It is the
      authors' impression that the percentage of cases of SLAP lesion repairs reported
      by young orthopaedic surgeons is high and that complications associated with this
      are not insignificant. STUDY DESIGN: Cohort study; level of evidence, 3. METHODS:
      We searched the American Board of Orthopedic Surgery (ABOS) part II database to
      evaluate changes in treatment over time and to identify available outcomes and
      associated complications of arthroscopic repair of SLAP lesions. The database was
      searched for all SLAP lesions (ICD-9 code 840.7) and SLAP repairs (CPT code
      29807) for the years 2003 through 2008. Utilization was analyzed by geographic
      region and was also obtained based on applicant subspecialty declaration.
      RESULTS: There were 4975 SLAP repairs, representing 9.4% of all applicants'
      shoulder cases. Mean follow-up was 8.9 weeks because of the time-limited case
      collection period. There were 78.4% who were men, and 21.6% of patients were
      women. The percentage of shoulder cases that were SLAP repairs increased over the
      study period from 9.4% to 10.1% by 2008 (P = .0163). Mean age of male patients
      was 36.4 +/- 13.0 years, with a maximum of 85 years. Mean age of female patients
      was 40.9 +/- 14.0 years, with a maximum of 88 years. Pain was reported as absent
      in only 26.3% of patients at follow-up and function as normal in only 13.1%.
      There were 40.1% of applicants who self-reported their patients to have an
      excellent result. The self-reported complication rate was 4.4%. Declared sports
      medicine specialists had a higher percentage of SLAP repairs than did general
      orthopaedic surgeons: 12.4% versus 9.2%. CONCLUSION: The percentage of shoulder
      cases that are SLAP repairs reported by the candidates is 3 times the published
      incidence supported by the current literature. The large number of repairs in
      middle-aged and elderly patients is concerning. Focusing on educating young
      orthopaedic surgeons to appropriately recognize and treat symptomatic SLAP
      lesions may bring the rate of SLAP repairs down.

PMID- 22628154
TI  - A highly efficient turn-on fluorescent sensor for determination of water in
      organic solvents.
AB  - 2, 3 biphenyl quinoxaline 6-amine is a fluorescent compound in some organic
      solvents with an excitation wavelength at 435 nm and a fluorescence emission at
      518 nm. The fluorescence intensity of 2, 3 biphenyl quinoxaline 6-amine is
      significantly reduced in the presence of bis-(2, 4, 6-trichlorophenyl) oxalate
      (TCPO) and Zn(2+) due to the nonfluorescent complex formation. The low stability
      of the complex in presence of trace amount of water results in decomposing
      complex, thereby recovering the photoluminescence of 2, 3 biphenyl quinoxaline 6
      amine. Based on this fact, a turn-on fluorescence photoluminescence sensor for
      determination of water content in organic solvents was introduced for the first
      time.The fluorescence intensity of 2, 3 biphenyl quinoxaline 6-amine as a
      function of water concentration was used as a simple, sensitive and rapid method
      for determining trace amount of water in some organic solvents such as ethanol
      and methanol. The obtained results showed a good linear relationship between
      fluorescence intensity and the water content with a dynamic range of 0.0094 
      1(v/v%), related coefficient of 0.9922 and limit of detection of 0.0026(v/v%).
      %).

PMID- 22628155
TI  - Genesis and intersubjectivity: levels of mediation.
AB  - I will make a brief comment on the thesis of Jose C. Loredo-Narciandi and Jose C.
      Sanchez-Gonzalez (2012) "Neither Dichotomies Nor Dualism; Simply Genesis".
      Denying any reductionism and reification, they insists the importance of
      inseparable relation between subject and object, then discuss about genesis. I
      pointed out that their argument lacks an important element, i.e., mediator that
      differ from mere physical object. After discussing mediators nature, I
      discriminate the three level of interaction which mediated by mediator. The first
      is the pre-interaction level, the second is physical interaction level and the
      third is sign or language interaction level. The last argument of mine is about
      how we can solve the problem of reification and reductionism. In the argument it
      is pointed out that intersubjectivity is key concept for understanding and
      solving the problem appropriately.

PMID- 22628156
TI  - Polyphenolic acetylcholinesterase inhibitors from Hopea chinensis.
AB  - Bioassay-guided investigation of the stem bark of Hopea chinensis led to the
      isolation of two new polyphenols, hopeachinols C(1) and D(2), together with ten
      known compounds (3-12). Compounds 1 and 2 were determined by extensive analysis
      of spectroscopic data and computational methods. All of these phytochemicals were
      tested for acetylcholinesterase inhibitory activity, and five resveratrol-derived
      compounds (1 and 7-10) exhibited significant activity with their IC50 values
      ranging from 4.81 to 11.71 uM.

PMID- 22628158
TI  - Screening for DSM-IV-TR cognitive disorder NOS in Parkinson's disease using the
      Mattis Dementia Rating Scale.
AB  - OBJECTIVE: This study explores the utility of the Mattis Dementia Rating Scale
      (MDRS) as a screening tool for the Diagnostic and Statistical Manual for Mental
      Disorders 4th edition (DSM-IV-TR) diagnosis cognitive disorder not otherwise
      specified (NOS) in Parkinson's disease (PD). METHODS: A total of 125 individuals
      with PD were diagnosed using DSM-IV-TR criteria for cognitive disorder NOS and
      dementia. Receiver operating characteristics (ROC) tested the discriminant
      validity of the MDRS, with the clinician's diagnosis serving as the gold
      standard. RESULTS: The MDRS ROC curve to discriminate subjects with cognitive
      disorder NOS from non-demented subjects had an area under the curve of 0.59
      (standard error = 0.08, 95% CI: 0.43-0.74). CONCLUSIONS: The MDRS is not
      effective for identifying PD patients with cognitive disorder NOS without
      dementia.

PMID- 22628157
TI  - Genome-wide association study of neurocognitive impairment and dementia in HIV
      infected adults.
AB  - The neuropathogenesis of HIV-associated neurocognitive disorders (HAND) is
      unclear. Candidate gene studies have implicated genetic susceptibility loci
      within immune-related genes; however, these have not been reliably validated.
      Here, we employed genome-wide association (GWA) methods to discover novel genetic
      susceptibility loci associated with HAND, and validate susceptibility loci
      implicated in prior candidate gene studies. Data from 1,287 participants enrolled
      in the Multicenter AIDS Cohort Study between 1985 and 2010 were used. Genotyping
      was conducted with Illumina 1M, 1MDuo, or 550K platform. Linear mixed models
      determined subject-specific slopes for change over time in processing speed and
      executive functioning, considering all visits including baseline and the most
      recent study visit. Covariates modeled as fixed effects included: time since the
      first visit, depression severity, nadir CD4+ T-cell count, hepatitis C co
      infection, substance use, and antiretroviral medication regimen. Prevalence of
      HIV-associated dementia (HAD) and neurocognitive impairment (NCI) was also
      examined as neurocognitive phenotypes in a case-control analysis. No genetic
      susceptibility loci were associated with decline in processing speed or executive
      functioning among almost 2.5 million single nucleotide polymorphisms (SNPs)
      directly genotyped or imputed. No association between the SNPs and HAD or NCI
      were found. Previously reported associations between specific genetic
      susceptibility loci, HIV-associated NCI, and HAD were not validated. In this
      first GWAS of HAND, no novel or previously identified genetic susceptibility loci
      were associated with any of the phenotypes examined. Due to the relatively small
      sample size, future collaborative efforts that incorporate this dataset may still
      yield important findings.

PMID- 22628159
TI  - Defining essential stem cell characteristics in adipose-derived stromal cells
      extracted from distinct anatomical sites.
AB  - The discovery of adipose-derived stromal cells (ASCs) has created many
      opportunities for the development of patient-specific cell-based replacement
      therapies. We have isolated multiple cell strains of ASCs from various anatomical
      sites (abdomen, arms/legs, breast, buttocks), indicating widespread distribution
      of ASCs throughout the body. Unfortunately, there exists a general lack of
      agreement in the literature as to their "stem cell" characteristics. We find that
      telomerase activity and expression of its catalytic subunit in ASCs are both
      below the levels of detection, independent of age and culturing conditions. ASCs
      also undergo telomere attrition and eventually senesce, while maintaining a
      stable karyotype without the development of spontaneous tumor-associated
      abnormalities. Using a set of cell surface markers that have been promoted to
      identify ASCs, we find that they failed to distinguish ASCs from normal
      fibroblasts, as both are positive for CD29, CD73 and CD105 and negative for CD14,
      CD31 and CD45. All of the ASC isolates are multipotent, capable of
      differentiating into osteocytes, chondrocytes and adipocytes, while fibroblasts
      show no differentiation potential. Our ASC strains also show elevated expression
      of genes associated with pluripotent cells, Oct-4, SOX2 and NANOG, when compared
      to fibroblasts and bone marrow-derived mesenchymal stem cells (BM-MSCs), although
      the levels were lower than induced pluripotent stem cells (iPS). Together, our
      data suggest that, while the cell surface profile of ASCs does not distinguish
      them from normal fibroblasts, their differentiation capacity and the expression
      of genes closely linked to pluripotency clearly define ASCs as multipotent stem
      cells, regardless of tissue isolation location.

PMID- 22628160
TI  - Ultra-structural identification of interstitial cells of Cajal in the zebrafish
      Danio rerio.
AB  - The interstitial cells of Cajal (ICCs) are important mediators of
      gastrointestinal (GI) motility because of their role as pacemakers in the GI
      tract. In addition to their function, ICCs are also structurally distinct cells
      most easily identified by their ultra-structural features and expression of the
      tyrosine kinase receptor c-KIT. ICCs have been described in mammals, rodents,
      birds, reptiles, and amphibians, but there are no reports at the ultra-structural
      level of ICCs within the GI tract of an organism from the teleost lineage. We
      describe the presence of cells in the muscularis of the zebrafish intestine;
      these cells have similar features to ICCs in other vertebrates. The ICC-like
      cells are associated with the muscularis, are more electron-dense than
      surrounding smooth muscle cells, possess long cytoplasmic processes and
      mitochondria, and are situated opposing enteric nervous structures. In addition,
      immunofluorescent and immunoelectron-microscopic studies with antibodies
      targeting the zebrafish ortholog of a putative ICC marker, c-KIT (kita), showed c
      kit immunoreactivity in zebrafish ICCs. Taken together, these data represent the
      first ultra-structural characterization of cells in the muscularis of the
      zebrafish Danio rerio and suggest that ICC differentiation in vertebrate
      evolution dates back to the teleost lineage.

PMID- 22628161
TI  - The expression of the PIWI family members miwi and mili in mice testis is
      negatively affected by estrogen.
AB  - PIWI family members miwi and mili as a constituent part of the piRNA pathway play
      a crucial role in germline maintenance, differentiation and meiosis conserved in
      mammals. A previous study shows estrogen could regulate the piwi pathway and
      determine the gonadal sex differentiation in lower animals. In this study, we
      expose mouse testis relative cells or tissues in different concentrations and a
      continuous time series, using quantitative RT-PCR, flow cytometry and
      immunohistochemical techniques for analyses of the influence over miwi and mili
      in vitro and in vivo. The in vitro studies show estrogen can downregulate the
      expression of miwi and mili. A similar pattern is observed in the first several
      days and then later back to normal in vivo. Our result indicates that estrogen
      can decrease expression of miwi and mili in male testis.

PMID- 22628162
TI  - Regional dynamics of amyloid-beta deposition in healthy elderly, mild cognitive
      impairment and Alzheimer's disease: a voxelwise PiB-PET longitudinal study.
AB  - Amyloid-beta deposition in Alzheimer's disease is thought to start while
      individuals are still cognitively unimpaired and it is hypothesized that after an
      early phase of fast accumulation, a plateau is reached by the time of cognitive
      decline. However, few longitudinal Pittsburgh compound B-positron emission
      tomography studies have tested this hypothesis, and with conflicting results. The
      purpose of this work is to further our understanding of the dynamics of amyloid
      beta deposition in a large longitudinal cohort. A total of 32 patients with
      Alzheimer's disease, 49 subjects with mild cognitive impairment and 103 healthy
      controls underwent two Pittsburgh compound B-positron emission tomography scans
      18 months apart. For each participant, a parametric map of Pittsburgh compound B
      positron emission tomography rate of change was created [(follow-up scan -
      baseline scan)/follow-up duration] and entered in a voxelwise three-way analysis
      of covariance, with clinical status (healthy controls, mild cognitive impairment
      or Alzheimer's disease), disease progression (clinical conversion from healthy
      controls to mild cognitive impairment or Alzheimer's disease, or from mild
      cognitive impairment to Alzheimer's disease) and Pittsburgh compound B status
      (positive versus negative) as independent factors. Only a significant effect of
      the Pittsburgh compound B status was found: both Pittsburgh compound B-positive
      and -negative subjects showed a significant increase in amyloid-beta deposition,
      with this increase being significantly higher in Pittsburgh compound B-positive
      individuals. This finding suggests either that Pittsburgh compound B-negative
      individuals have slower rates of amyloid-beta accumulation than positive, or that
      the proportion of individuals showing significant increase in amyloid-beta
      deposition, termed 'Pittsburgh compound B accumulators', is higher within the
      Pittsburgh compound B-positive group than within the Pittsburgh compound B
      negative group. The bimodal distribution of the individual rates of neocortical
      amyloid-beta accumulation observed support the existence of 'Pittsburgh compound
      B non-accumulators' and 'Pittsburgh compound B accumulators' and different
      clustering analyses led to a consistent threshold to separate these two subgroups
      (0.014-0.022 standardized uptake value ratio(pons)/year). The voxelwise three-way
      analysis of covariance was thus recomputed with the 'Pittsburgh compound B
      accumulators' only and the results were almost unchanged, with the Pittsburgh
      compound B-positive group showing higher accumulation than the Pittsburgh
      compound B-negative group. Finally, a significant negative correlation was found
      between Pittsburgh compound B rate of change and Pittsburgh compound B baseline
      burden, but only in the Pittsburgh compound B-positive group (r= -0.24; P=0.025).
      Higher rates of amyloid-beta deposition are associated with higher amyloid-beta
      burden suggesting that amyloid-beta deposition does not reach a plateau when
      cognitive impairments manifest but is instead an ongoing process present even at
      the Alzheimer's disease stage. amyloid-beta accumulation also seems to slow down
      at the latest stages of the process, i.e. in participants with the highest
      amyloid burden. Furthermore, this study identified the existence of Pittsburgh
      compound 'accumulators' and 'non-accumulators', notably within the Pittsburgh
      compound B-negative group, which may be a relevant concept for future studies.

PMID- 22628163
TI  - Effect of intestinal first-pass hydrolysis on the oral bioavailability of an
      ester prodrug of fexofenadine.
AB  - The contribution of intestinal first-pass hydrolysis to oral bioavailability was
      evaluated in rats using a model prodrug of fexofenadine (FXD), which has poor
      oral bioavailability. The prodrug, ethyl-FXD, has high membrane permeability but
      the oral bioavailability of FXD derived from ethyl-FXD was only 6.2%. Ethyl-FXD
      was not detected in the plasma, whereas FXD was detected, indicating complete
      first-pass hydrolysis. In in vitro experiments, hydrolase activity for ethyl-FXD
      was higher in the liver and blood than that in the intestine. However, the high
      blood protein binding of ethyl-FXD resulted in a high hepatic availability (F(h)
      = 88%). The complete bioconversion of ethyl-FXD in the in vivo oral
      administration is difficult to explain by first-pass hydrolysis in the liver and
      blood. Interestingly, in an in situ rat jejunal single-pass perfusion experiment,
      84% of the ethyl-FXD taken up into enterocytes was hydrolyzed. Furthermore, only
      one-fifth of the FXD formed in mucosa reached the mesenteric vein because of its
      P-glycoprotein-mediated efflux into the intestinal lumen. These findings indicate
      that the intestinal bioconversion of ester prodrugs to their parent drugs is a
      key factor in determining their oral bioavailability.

PMID- 22628164
TI  - Photoactivation of bone marrow mesenchymal stromal cells with diode laser:
      effects and mechanisms of action.
AB  - Mesenchymal stromal cells (MSCs) are a promising cell candidate in tissue
      engineering and regenerative medicine. Their proliferative potential can be
      increased by low-level laser irradiation (LLLI), but the mechanisms involved
      remain to be clarified. With the aim of expanding the therapeutic application of
      LLLI to MSC therapy, in the present study we investigated the effects of 635 nm
      diode laser on mouse MSC proliferation and investigated the underlying cellular
      and molecular mechanisms, focusing the attention on the effects of laser
      irradiation on Notch-1 signal activation and membrane ion channel modulation. It
      was found that MSC proliferation was significantly enhanced after laser
      irradiation, as judged by time lapse videomicroscopy and EdU incorporation. This
      phenomenon was associated with the up-regulation and activation of Notch-1
      pathway, and with increased membrane conductance through voltage-gated K(+) , BK
      and Kir, channels and T- and L-type Ca(2+) channels. We also showed that MSC
      proliferation was mainly dependent on Kir channel activity, on the basis that the
      cell growth and Notch-1 up-regulation were severely decreased by the pre
      treatment with the channel inhibitor Ba(2+) (0.5 mM). Interestingly, the channel
      inhibition was also able to attenuate the stimulatory effects of diode laser on
      MSCs, thus providing novel evidence to expand our knowledge on the mechanisms of
      biostimulation after LLLI. In conclusions, our findings suggest that diode laser
      may be a valid approach for the preconditioning of MSCs in vitro prior cell
      transplantation.

PMID- 22628165
TI  - Functional study of dextran-graft-poly((2-dimethyl amino)ethyl methacrylate) gene
      delivery vector for tumor therapy.
AB  - The obstacle of gene therapy is the shortage of efficient delivery system. The
      development of the gene delivery system with high transfection efficiency and low
      toxicity appears to be crucial. Recently, we reported that the dextran-graft
      poly((2-dimethyl amino)ethyl methacrylate) (DPD) can be potentially used as
      efficient gene vector. Herein, DPD was systematically studied for its potential
      in tumor gene therapy. DPD was synthesized and characterized by agarose gel
      electrophoresis, particle size and zeta potential. The particle size and zeta
      potential of the DPD/enhanced green fluorescent protein (pEGFP-C1) plasmid
      complexes at various N/P ratios were 130-150 nm and about 40 mV, respectively.
      The results showed that DPD exhibit a higher transfection effect compared with
      Lipofectamine 2K (Lipo 2K), a commercialized vector. The possibility of DPD in
      gene therapy was evaluated using p53, a gene that has been wildly applied in the
      research of cancer gene therapy. DPD/pEGFP-C1-p53 complex was found to be able to
      inhibit tumor cell proliferation through cell cycle arrest and apoptosis.
      Moreover, the tumor growth was found to be restrained when DPD/pEGFP-C1-p53
      complex was used in a xenograft MCF7 tumor model in vivo. These observations
      indicated that DPD/pEGFP-C1-p53 complex may be considered to be an efficient
      delivery system for tumor gene therapy. 

PMID- 22628166
TI  - Phosphorus(III) cations supported by a PNP pincer ligand and sub-stoichiometric
      generation of P4 from thermolysis of a nickel insertion product.
AB  - Neutral, mono-, and dicationic phosphorus(III) compounds are accessible with a
      supporting PNP pincer ligand (PNP = [4-Me-2-iPr(2)P-C(6)H(3))(2)N]). Reaction of
      (PNP)H with PCl(3) and nBu(3)N furnished (PNP)PCl(2) (1), which displays a highly
      temperature-dependent structure in solution. Synthesis and characterization by
      NMR spectroscopy and X-ray crystallography of Cl/Br-scrambled derivatives, a
      monocationic derivative [(PNP)PCl][HCB(11)H(11)] (4), and the dicationic
      derivatives [(PNP)P][OTf](2) (5), [(PNP)P][B(C(6)F(5))(4)](2) (6),
      [(PNP)P][B(12)Cl(12)] (7) established that 1 not only undergoes several fluxional
      processes in solution but also possesses a temperature-dependent ground state
      structure. Reaction of 1 with a Ni(0) source initially leads to a phosphine
      phosphinidene complex, followed by thermal generation of P(4).

PMID- 22628167
TI  - Self-organization of hydrogen-bonding naphthalene chromophores into J-type
      nanorings and H-type nanorods: impact of regioisomerism.

PMID- 22628168
TI  - The Spanish tobacco tax loopholes and their consequences.
AB  - OBJECTIVES: The Spanish government has strengthened tobacco control policies
      since 2005, including changes in tobacco taxes. Because these changes have
      targeted cigarettes mainly, the tobacco industry has marketed cheaper alternative
      tobacco products, offering smokers the possibility to downtrade. This paper
      traces the evolution of patterns of demand for cigarettes and other tobacco
      products in Spain over the period 2005-2011 in order to assess the impact of such
      tax loopholes. METHODS: The authors use data on tobacco products prices and sales
      as well as changes in the structure and levels of tobacco taxes to relate tax
      changes to price changes and subsequent market share changes. RESULTS: Tax
      reforms have lifted the bottom end of the cigarette price distribution, but the
      industry has been successful in marketing fine-cut tobacco at cheap prices. There
      have been partial attempts to correct this asymmetric tax treatment, but these
      have not avoided a remarkable increase in the market share of fine-cut tobacco.
      The absence of a minimum tax on quantity for the rest of tobacco products allows
      the industry to place them as potential future downtrading vehicles. CONCLUSIONS:
      In order to address public health objectives, tax policies should aim to equalise
      the cost of smoking across different tobacco products. Otherwise the tobacco
      industry can exploit tax loopholes to market cheap alternatives to cigarettes.
      This requires all tobacco products to bear a minimum tax on quantity, whose
      levels need to be adjusted in order to reflect the equivalence between different
      forms of smoking.

PMID- 22628169
TI  - Using findings from a public opinion poll to build political support for tobacco
      control policy in Kenya.
AB  - OBJECTIVE: To assess the level of public support for tobacco control policies and
      to discuss how these findings could be used to influence the legislative process
      in the passing of tobacco control law in the country. METHODS: A cross-sectional
      study conducted in Kenya between March and May 2007 on a random sample of 2021
      (991 men and 1030 women) respondents aged 18 years and above. Interviews were
      done using a structured questionnaire by a research consultancy firm with long
      standing experience in public polling. RESULTS: The majority of respondents
      supported tobacco control policies as proposed by WHO Framework Convention on
      Tobacco Control. For example, 95% of the respondents supported smoking
      restrictions in all enclosed public places and workplaces, 94% supported visible
      health warnings on tobacco product packages, 83% supported a ban on
      advertisements of cigarettes and tobacco products and 69% supported a ban on
      sponsorship of events by tobacco companies. However, 60% perceived that there was
      very little commitment by legislators to tobacco control. CONCLUSIONS: There was
      overwhelming public support for tobacco control policies and a general view that
      government was not doing enough in implementing policies to protect the public
      from tobacco harm. This public opinion poll was used as an advocacy tool to
      generate support among legislators for national tobacco control law.

PMID- 22628170
TI  - Intergenerational transmission of gambling: links between young adult and
      perceived grandparent gambling attitudes and behavior.
AB  - This study examined associations between the gambling attitudes and behavior of
      213 young adults and their perceptions of the gambling attitudes and behavior of
      their closest grandparent. Regression analyses showed that young adult gambling
      attitudes mediated the relations between perceived grandparent gambling attitudes
      and behavior and young adult gambling behavior. Grandparent-grandchild
      relationship quality experienced while growing up did not moderate the relations
      between young adult and perceived grandparent gambling attitudes and behavior.
      Men experienced gambling at a younger age and reported more positive gambling
      attitudes, more frequent gambling activity, higher levels of gambling pathology,
      and higher levels of gambling affinity than women. Implications of results and
      suggestions for future research are discussed. 

PMID- 22628171
TI  - Resistance risk assessment within herbicide authorisation--a call for sensitivity
      data.
AB  - In most European countries, the risk of herbicide resistance is assessed as part
      of the authorisation of herbicides in accordance with EPPO Standard PP 1/213(2).
      Because the susceptibility of weed populations to a certain herbicide may vary
      greatly, one part of resistance risk assessment is the testing for sensitivity
      variation among different populations of target weed species with a high
      resistance risk. This paper emphasises the importance of sensitivity data
      provision with regard to the recent EU Regulation (EC) 1107/2009 concerning the
      placing of plant protection products on the market and outlines the main
      technical requirements for sensitivity data. A useful principle is that
      sensitivity data should be provided for all herbicides with a high resistance
      risk regardless of whether resistance has already evolved against the herbicidal
      substance. Methodical details regarding the generation of sensitivity data are
      discussed, together with remaining questions that will need to be addressed if a
      harmonised assessment of herbicide resistance risk is to be achieved.

PMID- 22628172
TI  - A simplified equation for adult BMI growth, and its use to adjust BMI for age.

PMID- 22628173
TI  - Enhanced arsenate uptake in Saccharomyces cerevisiae overexpressing the Pho84
      phosphate transporter.
AB  - Arsenate is a major toxic constituent in arsenic-contaminated water supplies.
      Saccharomyces cerevisiae was engineered as a potential biosorbent for enhanced
      arsenate accumulation. The phosphate transporter, Pho84p, known to import
      arsenate, was overexpressed using a 2MU-based vector carrying PHO84 under the
      control of the late-phase ADH2 promoter. Arsenate uptake was then evaluated using
      a resting cell system. In buffer solutions containing high arsenate
      concentrations (12,000 and 30,000 ppb), the engineered strains internalized up to
      750 MUg of arsenate per gram of cells, a 50% improvement over control strains.
      Increasing the cell mass 2.5-fold yielded a proportional increase in the
      volumetric arsenate uptake, while maintaining the same level of specific uptake.
      At high levels of arsenate, loss from the intact cells to the medium was observed
      with time; knockouts of two known arsenic extrusion genes, ACR3 and FPS1, did not
      prevent this loss. At trace level concentrations (120 ppb), rapid and total
      arsenate removal was observed. The presence of 50 MUM phosphate reduced uptake by
      approximately 15% in buffer containing 80 MUM (6,000 ppb) arsenate. At trace
      levels of arsenate (70 ppb), the phosphate reduced the initial rate of uptake,
      but not the total amount removed. PHO84 mRNA levels were nearly 30 times higher
      in the engineered strains relative to the control strains. Uptake may no longer
      be a limiting factor in the engineered system and further increases should be
      possible by upregulating the downstream reduction and sequestration pathways.

PMID- 22628174
TI  - beta1 -adrenergic receptor autoantibodies from heart failure patients enhanced
      TNF-alpha secretion in RAW264.7 macrophages in a largely PKA-dependent fashion.
AB  - Autoantibodies against the second extracellular loop of beta(1) -adrenergic
      receptor (beta(1) -AA) not only contribute to increased susceptibility to heart
      failure, but also play a causative role in myocardial remodeling through their
      catecholamine-like effects via binding with the beta(1) -adrenergic receptor. The
      current study was designed to determine whether beta(1) -AA isolated from the
      sera of heart failure patients could cause TNF-alpha secretion from the murine
      macrophage-like cell line RAW264.7. Blood samples were collected from 40 patients
      who had suffered heart failure, as well as from 40 healthy subjects. The titer of
      beta(1) -AA and the level of TNF-alpha were detected using ELISA. The effect of
      beta(1) -AA on murine macrophage-like cell line RAW264.7 proliferation was
      detected by CCK-8 kits and CFSE assay. Western blot assay was used to analyze the
      expression of phospho-VASP. beta(1) -AA appeared more frequently in patients with
      heart failure than in healthy subjects. The beta(1) -AA isolated from heart
      failure patients promoted an increase of TNF-alpha levels, which could be
      completely blocked by the selective beta(1) -adrenergic receptor antagonist
      metoprolol and the second extracellular loop of beta(1) -adrenergic receptor
      (beta(1) -AR-EC(II) ), but only partially inhibited by PKA inhibitor H89.
      Furthermore, the beta(1) -AA could enhance the proliferation of RAW264.7 cells in
      vitro. Meanwhile, the expression of phospho-VASP was markedly increased in the
      presence of beta(1) -AA. These results demonstrate for the first time that the
      beta(1) -AA isolated from heart failure patients could bind with beta(1) -AR on
      the surface of RAW264.7 cells, causing the release of TNF-alpha largely in a PKA
      dependent fashion.

PMID- 22628175
TI  - Contemporary management of femoral neck fractures: the young and the old.
AB  - The optimal management strategy for femoral neck fractures remains highly
      debated. The femoral neck is intracapsular and the vascular supply is fragile.
      Furthermore, the curvature of the proximal femur results in high mechanical
      stresses through the femoral neck. Poor outcomes of nonunion and avascular
      necrosis (AVN) are common. This chapter reviews the current evidence with respect
      to the treatment principles of femoral neck fractures in two distinct patient
      populations: "young" and "old." Contemporary controversies including surgical
      timing, choice of implant, arthroplasty options, nonoperative management,
      capsulotomy, and associated complications will be discussed.

PMID- 22628176
TI  - Femoral head fractures.
AB  - Femoral head fractures may present in various patterns with or without associated
      fractures around the hip. As a result, the treating orthopaedic surgeon must
      understand not only the fracture pattern, but also patient-related fractures and
      the relevant operative exposures and reconstructive options to achieve the best
      functional outcome while minimizing complications. Treatment options range from
      non-operative treatment to fracture fragment excision or fracture fixation using
      various surgical exposures and implants. This article reviews the current
      literature on the treatment options for femoral head fractures and presents
      modern operative techniques that have improved exposure of the fracture while
      minimizing associated risks such as avascular necrosis, heterotopic ossification,
      and neurovascular compromise. A sound understanding of the anatomy and these
      newer techniques can enable the surgeon to provide improved expectations and
      clinical outcomes.

PMID- 22628177
TI  - Management of cartilage defects in the shoulder.
AB  - Articular cartilage lesions of the glenohumeral joint are an especially difficult
      clinical problem to manage, particularly in the younger, more active patient.
      Left untreated, these lesions may progress in the long-term, leading to further
      pain and disability. While shoulder arthroplasty remains a viable option in older
      patients with glenohumeral arthritis, concerns over component longevity and
      loosening in younger patients make it less attractive in that age group.
      Arthroscopic joint debridement with loose body removal, often with capsular
      release, has been successful in select, more sedentary patients. More recent
      techniques, including autologous chondrocyte implantation (ACI), osteochondral
      grafting (allograft versus autograft), interpositional arthroplasty, and
      microfracture surgery, have been evaluated for use in the shoulder. These
      procedures have experienced success in weight bearing joints, including the knee
      and ankle. Despite the good clinical results in the shoulder with short-term
      follow-up reported in some small series, the treatment of chondral injuries in
      the glenohumeral joint remains a challenging problem.

PMID- 22628178
TI  - The use of osteochondral allografts in the management of cartilage defects.
AB  - Large symptomatic osteochondral defects in a young active population represent a
      therapeutic challenge for orthopedic surgeons, since standard interventions such
      as debridement, microfracture and autologous osteochondral transfer are not
      suitable for the treatment of these larger lesions. Fresh osteochondral allograft
      transplantation provides a surgical option for these challenging defects, both as
      a primary procedure and for salvage of prior failed treatment attempts. This
      article reviews the basic science, indications, technique, and evidence for
      osteochondral allograft transplantation in the knee.

PMID- 22628179
TI  - Effectiveness of using clinical guidelines for conducting palliative care family
      meetings in Japan.
AB  - PURPOSE: The purpose of this study is to pilot test the effectiveness of using
      recently developed clinical guidelines from Australia for conducting palliative
      care family meetings in Japan. METHODS: Palliative care family meetings were
      conducted using clinical guidelines with 15 primary family carers of cancer
      patients who were admitted to an acute care hospital in Japan. Using the pre
      family meeting questionnaire, the primary carers were asked to write key concerns
      to discuss during the family meetings and rate their concerns via a numerical
      rating scale: how upset/worried they were about the problem, frequency in which
      problem occurs, life interference with the problem, and the confidence to deal
      with the problem. Within 3 days after the meeting, the primary carers were asked
      to complete the post-meeting questionnaire to evaluate the effectiveness of the
      family meeting. RESULTS: There was a significant improvement in family carers'
      psychological well-being in the post-meeting questionnaires compared to the pre
      meeting questionnaires as follows: how upset/worried they were about the problem,
      t(14) = 3.1071, p < 0.000011; frequency in which problem occurs, t(14) = 3.2857,
      p < 0.000013; life interference with the problem, t(14) = 2.7857, p < 0.000008;
      and the confidence to deal with the problem, t(13) = -2.3007, p < 0.005480.
      CONCLUSIONS: In accordance with the study aims, we were able to demonstrate the
      utility of a questionnaire as an essential tool to plan and conduct effective
      communication between health professionals and primary family carers in Japanese
      cancer patients. This pilot test should be followed up with a larger sample and a
      controlled trial.

PMID- 22628181
TI  - [Endoscopic treatment for tumorous obstructions of the tracheobronchial system: a
      comparison of available techniques].
AB  - Malignant central airway obstruction is a common problem in lung cancer. A
      symptomatic stenosis can often be treated successfully using endoscopy. Different
      approaches for recanalisation are available. The goal of treating exophytic
      obstruction is to remove the endobronchial tumour growth. Mechanic debulking,
      electrocautery/diathermy, argon plasma coagulation, laser resection and
      cryoextraction are techniques that can provide immediate relief. Cryotherapy,
      brachytherapy and photodynamic therapy show delayed recanalisation effects.
      Silicone or self-expanding metallic airway stents can be used for the treatment
      of airway obstruction due to extrinsic disease to restore and maintain airway
      patency.

PMID- 22628180
TI  - Genome-wide association uncovers shared genetic effects among personality traits
      and mood states.
AB  - Measures of personality and psychological distress are correlated and exhibit
      genetic covariance. We conducted univariate genome-wide SNP (~2.5 million) and
      gene-based association analyses of these traits and examined the overlap in
      results across traits, including a prediction analysis of mood states using
      genetic polygenic scores for personality. Measures of neuroticism, extraversion,
      and symptoms of anxiety, depression, and general psychological distress were
      collected in eight European cohorts (n ranged 546-1,338; maximum total n = 6,268)
      whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results
      was performed, with follow-up associations of the top SNPs and genes investigated
      in independent cohorts (n = 527-6,032). Suggestive association (P = 8 * 10(-8))
      of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other
      notable associations (P < 6.09 * 10(-6)) included SNPs in five genes for
      neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and
      NOS1 for general psychological distress. An association between symptoms of
      depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two
      independent samples, but other replication findings were less consistent. Gene
      based tests identified a significant locus on chromosome 15 (spanning five genes)
      associated with neuroticism which replicated (P < 0.05) in an independent cohort.
      Support for common genetic effects among personality and mood (particularly
      neuroticism and depressive symptoms) was found in terms of SNP association
      overlap and polygenic score prediction. The variance explained by individual SNPs
      was very small (up to 1%) confirming that there are no moderate/large effects of
      common SNPs on personality and related traits.

PMID- 22628183
TI  - Naltrexone salt selection for enhanced transdermal permeation through microneedle
      treated skin.
AB  - The passive delivery rate of naltrexone (NTX) through intact skin is too slow to
      achieve therapeutic plasma levels in humans from a reasonably sized transdermal
      patch. A physical enhancement method--microneedles (MNs)--has been shown to
      afford a substantial increase in the percutaneous flux of NTX hydrochloride in
      vitro. However, for better therapeutic effect and decrease in the transdermal
      patch area, further enhancement is desired. The purpose of this study was to
      identify a NTX salt that would (1) provide elevated in vitro percutaneous drug
      transport across MN-treated skin as compared with that of the NTX hydrochloride
      and (2) prove nonirritating to the skin in vivo. The pH-solubility profiles of
      NTX salts were investigated with three drug salts showing improved solubility at
      physiologically relevant skin surface pH of 5.0. The skin-irritation potential of
      NTX glycolate and lactate gels was not greater than that of placebo gel in the
      guinea pig model. Additionally, in vitro diffusion studies indicated that NTX
      glycolate provides around 50% enhancement in the flux through MN-treated skin at
      the cost of doubling the drug concentration in the donor solution. Overall, a new
      NTX glycolate salt appears to be a promising candidate for MN-assisted
      transdermal drug delivery system.

PMID- 22628184
TI  - Mycobacterium smegmatis genomic characteristics associated with its saprophyte
      lifestyle.
AB  - Tuberculosis (TB) remains a great threat to global public health. The high
      biosafety level III required to tackle its causative agent Mycobacterium
      tuberculosis seriously hinders the exploration of its biology and new
      countermeasures. M. smegmatis is a widely recognized good surrogate of M.
      tuberculosis, largely due to their conserved transcriptional machinery, sigma
      factors, and two-component systems. However, their distinct lifestyles often
      confound the explanation of the results. M. tuberculosis leads both parasitic and
      free life, while M. smegmatis is largely saprophyte. To make full advantage of
      this model, it is helpful to discover the genome features associated with M.
      smegmatis unique niches, such as its saprophytic life, high salt tolerance, and
      relative short generation time. We employed the gene ontology enrichment analysis
      to characterize the unique lifestyle of M. smegmatis. Gene ontology enrichment
      analysis provided 12 terms; most are relevant to the special lifestyle of M.
      smegmatis, especially the saprophytic niche, high salt tolerance adaptation, and
      short generation time. In-depth functional characterization of these genes will
      shed new lights on the genetic basis of M. smegmatis saprophytic life and hasten
      the understanding of the unique biology of M. tuberculosis.

PMID- 22628182
TI  - A methodological approach to unravel organ-specific breast cancer metastasis.
AB  - Breast cancer is the most commonly diagnosed and the second highest cause of
      cancer-related mortality. Although major breakthroughs have emerged during the
      past decades concerning the characterization of major malignant tumors hallmarks,
      little is known about the molecular process that sustains the most deadly feature
      of cancer: metastasis to distant organs. In fact, this colonization of tumor
      cells to secondary sites is not random but rather orientated, and depends on
      several signalling events that are not fully elucidated yet. Understanding the
      precise molecular and cellular mechanisms accountable for the specific invasion
      of tissues by breast cancer cells is likely to be important for developing new
      therapeutic strategies to effectively prevent metastasis in patients diagnosed
      with early cancer lesions. Here, we briefly describe a multidisciplinary approach
      based on the molecular profiling of breast cancer metastases, the elaboration of
      prognostic gene signatures, the clinical validation and the experimental
      confirmation using cell and animal models to better address breast cancer
      metastasis. This methodology can be considered as a useful workflow to identify
      and validate the genes that trigger and support organ tropism of breast cancer
      cells during metastasis.

PMID- 22628185
TI  - Major, non-chromosomal, birth defects and maternal physical activity: a
      systematic review.
AB  - BACKGROUND: We reviewed the published literature to assess the association
      between maternal periconceptional physical activity and the risk for major, non
      chromosomal, birth defects and whether this varies by pre-pregnancy obesity.
      METHODS: We conducted a systematic literature search of MEDLINE, EMBASE, and
      CINAHL databases. Data were abstracted from all articles that met our inclusion
      criteria and included information on physical activity intensity (mild, moderate,
      and vigorous) and modality (i.e., standing, lifting, other). We assessed
      occupational and recreational physical activity separately. The quality of
      included articles was assessed using the Newcastle-Ottawa Scale. RESULTS: Of 3316
      screened articles, 11 were included in this review. Of the four studies that
      assessed prolonged standing, two reported a positive association with risk for
      some birth defects; null associations were observed in the other two studies.
      Associations between heavy lifting or other occupational physical activity
      exposures and risk for birth defects were inconsistent. A protective association
      between leisure-time physical activity (i.e., active sports, swimming) and some
      birth defects (e.g., neural tube defects), was suggested by the results of two
      studies. Only one study reported assessment of possible effect modification by
      maternal body mass index (BMI). DISCUSSION: Our review suggests that there may be
      some associations between occupational and leisure-time physical activities and
      some, major non-chromosomal, birth defects, but relatively limited published
      research exists on these associations. Further research in this area should
      include differentiation of birth defects phenotypes, valid assessments of all
      domains of physical activity, including household and transportation activity,
      and account for the potential influence of pre-pregnancy BMI.

PMID- 22628186
TI  - C. elegans feeding.
AB  - C. elegans feeding depends on the action of the pharynx, a neuromuscular pump
      that joins the mouth to the intestine. The pharyngeal muscle captures food
      bacteria-and transports it back to the intestine. It accomplishes this through a
      combination of two motions, pumping and isthmus peristalsis. Pumping, the most
      visible and best understood of the two, is a cycle of contraction and relaxation
      that sucks in liquid from the surrounding environment along with suspended
      particles, then expels the liquid, trapping the particles. Pharyngeal muscle is
      capable of pumping without nervous system input, but during normal rapid feeding
      its timing is controlled by two pharyngeal motor neuron types. Isthmus
      peristalsis, a posterior moving wave of contraction of the muscle of the
      posterior isthmus, depends on a third motor neuron type.  Feeding motions are
      regulated by the presence and quality of food in the worm's environment. Some
      types of bacteria are better at supporting growth than others. Given a choice,
      worms are capable of identifying and seeking out higher-quality food. Food
      availability and quality also affect behavior in other ways. For instance, given
      all the high-quality food they can eat, worms eventually become satiated, stop
      eating and moving, and become quiescent.

PMID- 22628187
TI  - Development of an O2-sensitive fluorescence-quenching assay for the combinatorial
      discovery of electrocatalysts for water oxidation.

PMID- 22628188
TI  - Critical capillary absorption of current-melted silver nanodroplets into
      multiwalled carbon nanotubes.

PMID- 22628190
TI  - Sequestering aromatic molecules with a spin-crossover Fe(II) microporous
      coordination polymer.
AB  - All in a spin: A series of three-dimensional porous coordination polymer
      {Fe(dpe)[Pt(CN)(4)]}?G (dpe = 1,2-di(4-pyridyl)ethylene; G = phenazine,
      anthracene, or naphthalene) exhibiting spin crossover and host-guest functions is
      reported. The magnetic properties of the framework are very sensitive to the
      chemical nature (aromatic or hydroxilic solvents) and the size of the included
      guest molecules.

PMID- 22628189
TI  - Feasibility of unmanipulated haploidentical stem cell transplantation using
      standard GVHD prophylaxis for HLA-homozygous patients.
AB  - HLA-haploidentical hematopoietic stem cell transplantation (haplo-SCT) in HLA
      homozygous patients is accompanied by HLA mismatches only in the host-versus
      graft vector, and thus theoretically could be performed with standard graft
      versus-host disease (GVHD) prophylaxis. However, the risk of GVHD remains
      uncertain, and graft failure could be a problem. In this study, we assessed nine
      HLA-homozygous patients who underwent haplo-SCT. Preparative treatment was
      cyclophosphamide/total body irradiation-based regimen in five patients,
      fludarabine/busulfan-based regimen in two, and other regimens in two. GVHD
      prophylaxis consisted of cyclosporine and methotrexate in seven patients,
      cyclosporine and mycophenolate mofetil in one, and cyclosporine alone in one.
      Seven patients achieved neutrophil engraftment and platelet recovery. The median
      times to neutrophil engraftment and platelet recovery were 15 and 44 days,
      respectively. Two patients developed graft failure, including one who achieved
      engraftment with a second SCT from the same donor. Grade II GVHD was observed in
      half of the evaluable patients; grades III and IV were not observed. Two patients
      died from treatment-related causes. Five patients were alive after a median
      follow-up period of 563 days. The probability of overall survival at 5 years was
      65 %. These findings may serve as a rationale for considering haplo-SCT as a
      treatment option for HLA-homozygous patients.

PMID- 22628191
TI  - From NMP to RAFT and thiol-ene chemistry by in situ functionalization of
      nitroxide chain ends.
AB  - A straightforward, novel strategy based on the in situ functionalization of
      polymers prepared by nitroxide-mediated polymerization (NMP), for the use as an
      extension toward block copolymers and post-polymerization modifications, has been
      investigated. The nitroxide end group is exchanged for a thiocarbonylthio end
      group by a rapid transfer reaction with bis(thiobenzoyl) disulfide to generate in
      situ reversible addition-fragmentation chain transfer (RAFT) macroinitiators.
      Moreover, not only have these macroinitiators been used in chain extension and
      block copolymerization experiments by the RAFT process but also a thiol
      terminated polymer is synthesized by aminolysis of the RAFT end group and
      subsequently reacted with dodecyl vinyl ether by thiol-ene chemistry.

PMID- 22628192
TI  - Polymer-directed crystallization of atorvastatin.
AB  - Living organisms secrete minerals composed of peptides and proteins, resulting in
      "mesocrystals" of three-dimensional-assembled composite structures. Recently,
      this biomimetic polymer-directed crystallization technique has been widely
      applied to inorganic materials, although it has seldom been used with drugs. In
      this study, the technique was applied to the drowning-out crystallization of
      atorvastatin using various polymers. Nucleation and growth at optimized
      conditions successfully produced composite crystals with significant polymer
      contents and unusual characteristics. Atorvastatin composite crystals containing
      polyethylene glycol, polyacrylic acid, polyethylene imine, and chitosan showed a
      markedly decreased melting point and heat of fusion, improved stability, and
      sustained-release patterns. The use of hydroxypropyl cellulose yielded a unique
      combination of enhanced in vitro release and improved drug stability under a
      forced degradation condition. The formation hypothesis of unique mesocrystal
      structures was strongly supported by an X-ray diffraction pattern and substantial
      melting point reduction. This polymer-directed crystallization technique offers a
      novel and effective way, different from the solid dispersion approach, to
      engineer the release, stability, and processability of drug crystals.

PMID- 22628193
TI  - miR-301a promotes pancreatic cancer cell proliferation by directly inhibiting Bim
      expression.
AB  - It is well known that microRNAs (miRNAs) play an important role in many diseases,
      including tumorigenesis. However, the mechanisms by which miRNAs regulate
      pancreatic cancer (PC) development remain poorly understood. In the present
      study, we assayed expression level of miR-301a in PC tissues by real-time PCR,
      and defined the target gene and biological function by luciferase reporter assay
      and Western blot analysis. We first verified that the expression level of miR
      301a was significantly increased in PC tissues. Moreover, miR-301a overexpression
      promoted PC cell proliferation, whereas its depletion decreased cell
      proliferation. We further demonstrated that miR-301a directly targeted 3'-UTR of
      Bim gene, and inhibited its protein expression in vitro and in vivo. Importantly,
      Bim re-expression reduced PC cell proliferation induced by miR-301a. These data
      suggest an important role of miR-301a in the molecular etiology of PC and
      implicate the potential application of miR-301a in PC therapy.

PMID- 22628194
TI  - Curved biodegradable microneedles for vascular drug delivery.
AB  - Curved biodegradable microneedles for application to the outer surface of blood
      vessels are produced to enhance drug delivery to vascular tissues suffering from
      hyperplasia or atherosclerosis. Spatially discrete thermal drawing and post
      annealing processes are employed to fabricate microneedles on a curved surface.
      Insertion of microneedles into arteries in vivo and ex vivo is demonstrated, and
      their mechanical properties and drug-delivery function are studied.

PMID- 22628195
TI  - Gel sculpture: moldable, load-bearing and self-healing non-polymeric
      supramolecular gel derived from a simple organic salt.
AB  - An easy access to a library of simple organic salts derived from tert
      butoxycarbonyl (Boc)-protected L-amino acids and two secondary amines
      (dicyclohexyl- and dibenzyl amine) are synthesized following a supramolecular
      synthon rationale to generate a new series of low molecular weight gelators
      (LMWGs). Out of the 12 salts that we prepared, the nitrobenzene gel of
      dicyclohexylammonium Boc-glycinate (GLY.1) displayed remarkable load-bearing,
      moldable and self-healing properties. These remarkable properties displayed by
      GLY.1 and the inability to display such properties by its dibenzylammonium
      counterpart (GLY.2) were explained using microscopic and rheological data. Single
      crystal structures of eight salts displayed the presence of a 1D hydrogen-bonded
      network (HBN) that is believed to be important in gelation. Powder X-ray
      diffraction in combination with the single crystal X-ray structure of GLY.1
      clearly established the presence of a 1D hydrogen-bonded network in the xerogel
      of the nitrobenzene gel of GLY.1. The fact that such remarkable properties
      arising from an easily accessible (salt formation) small molecule are due to
      supramolecular (non-covalent) interactions is quite intriguing and such easily
      synthesizable materials may be useful in stress-bearing and other applications.

PMID- 22628196
TI  - Highly dispersed surfactant-free nickel nanoparticles and their remarkable
      catalytic activity in the hydrolysis of ammonia borane for hydrogen generation.

PMID- 22628198
TI  - Freezing pattern and frost killing temperature of apple (Malus domestica) wood
      under controlled conditions and in nature.
AB  - The freezing pattern and frost killing temperatures of apple (Malus domestica
      Borkh.) xylem were determined by differential thermal analysis and infrared
      differential thermal analysis (IDTA). Results from detached or attached twigs in
      controlled freezing experiments and during natural field freezing of trees were
      compared. Non-lethal freezing of apoplastic water in apple xylem as monitored
      during natural winter frosts in the field occurred at -1.9 +/- 0.4  degrees C and
      did not change seasonally. The pattern of whole tree freezing was variable and
      specific to the environmental conditions. On detached twigs high-temperature
      freezing exotherms (HTEs) occurred 2.8 K below the temperature observed under
      natural frosts in the field with a seasonal mean of -4.7 +/- 0.5  degrees C.
      Microporous apple xylem showed freezing without a specific pattern within a few
      seconds in IDTA images during HTEs, which is in contrast to macroporous xylem
      where a 2D freezing pattern mirrors anatomical structures. The pith tissue always
      remained unfrozen. Increasing twig length increased ice nucleation temperature;
      for increased twig diameter the effect was not significant. In attached twigs
      frozen in field portable freezing chambers, HTEs were recorded at a similar mean
      temperature (-4.6 +/- 1.0  degrees C) to those for detached twigs. Upon lethal
      intracellular freezing of apple xylem parenchyma cells (XPCs) low-temperature
      freezing exotherms (LTEs) can be recorded. Low-temperature freezing exotherms
      determined on detached twigs varied significantly between a winter minimum of 
      36.9  degrees C and a summer maximum -12.7  degrees C. Within the temperature
      range wherein LTEs were recorded by IDTA in summer (-12.7 +/- 0.5 to -20.3 +/-
      1.1  degrees C) various tiny clearly separated discontinuous freezing events
      could be detected similar to that in other species with contrasting XPC anatomy.
      These freezing events appeared to be initially located in the primary and only
      later in the secondary xylem. During the LTE no freezing events in the bark and
      central pith tissue were recorded. Attached twigs were exposed to various
      freezing temperatures at which LTEs occur. Even if 60% of XPCs were frost-damaged
      twigs were able to recuperate and showed full re-growth indicating a high
      regeneration capacity even after severe frost damage to XPCs.

PMID- 22628199
TI  - Preparation, characterizations, and in vitro metabolic processes of paclitaxel
      loaded discoidal recombinant high-density lipoproteins.
AB  - Discoidal recombinant high-density lipoproteins (d-rHDLs) are attractive
      candidates for anticancer agents because of their favorable biocompatibility,
      biodegradability, and receptor-mediated endocytosis. Paclitaxel (PTX)-loaded d
      rHDLs (P-d-rHDLs) were prepared by thin-film dispersion/detergent dialysis
      methods in this study. To investigate metabolic processes that P-d-rHDLs probably
      encounter in circulation, influences of lecithin-cholesterol acyltransferase
      (LCAT) on structural and compositional changes of P-d-rHDLs were studied in
      vitro. The shape of P-d-rHDLs converted from discoid into sphere, particle size
      increased, and cholesteryl ester (CE) generated simultaneously, which were
      referred to as remodeling behaviors. In vitro releases tests showed that release
      rate of PTX from P-d-rHDLs became faster when LCAT was added to P-d-rHDLs
      suspensions. Human breast cancer cells' cytotoxicity and cellular uptake of P-d
      rHDLs were higher than liposomes and Taxol, and decreased in the presence of
      LCAT. Explorations of above phenomena found that drug entrapment did not
      influence remodeling processes induced by LCAT, whereas there was drug leakage
      occurring in remodeling processes. Therefore, drug leakage resulting from
      remodeling processes under the action of LCAT should be paid more attentions to
      when using d-rHDLs as drug vehicles for anticancer drugs. This study first
      focuses on metabolic processes of drug carriers and elucidates them through in
      vitro tests.

PMID- 22628200
TI  - BMP2 induces osteoblast apoptosis in a maturation state and noggin-dependent
      manner.
AB  - Large doses of bone morphogenetic protein 2 (BMP2) are used clinically to induce
      bone formation in challenging bone defects. However, complications after
      treatment include swelling, ectopic bone formation, and adjacent bone resorption.
      While BMP2 can be effective, it is important to characterize the mechanism of the
      deleterious effects to optimize its use. The aim of this study was to determine
      the effect of BMP2 on apoptosis in osteoblast lineage cells and to determine the
      role of the BMP inhibitor Noggin in this process. Human mesenchymal stem cells
      (MSCs), immature osteoblast-like MG63 cells, and mature normal human osteoblasts
      (NHOst) were treated with BMP2. A model system of increased endogenous BMP
      signaling was created by silencing Noggin (shNOG-MG63). Finally, the BMP pathway
      regulating apoptosis in NHOst was examined using BMP signaling inhibitors (5Z-7
      oxozeaenol, dorsomorphin, H-8). Apoptosis was characterized by caspase-3,
      BAX/BCL2, p53, and DNA fragmentation. BMP2 induced apoptosis in a cell-type
      dependent manner. While the effect was minor in MSCs, MG63 cells had modest
      increases and NHOst cells had robust increases apoptosis after BMP2 treatment.
      Apoptosis was significantly higher in shNOG-MG63 than MG63 cells. 5Z-7-oxozeaenol
      and dorsomorphin eliminated the BMP2-induced increase in DNA fragmentation in
      NHOst, suggesting roles for TAB/TAK1 and Smad signaling. These results indicate
      that the apoptotic effect of BMP2 is dependent on cell maturation state, inducing
      apoptosis in committed osteoblasts through Smad and TAB/TAK1 signaling, and is
      regulated by Noggin. Dose and delivery must be optimized in therapeutic
      applications of BMP2 to minimize complications.

PMID- 22628201
TI  - Differential effects of radiotherapy on growth and endocrine function among acute
      leukemia survivors: a childhood cancer survivor study report.
AB  - BACKGROUND: The differential effects of cranial radiotherapy (CRT), spinal
      radiotherapy (SRT), and total body irradiation (TBI) on growth and endocrine
      outcomes have rarely been examined in combination among childhood acute leukemia
      survivors. PROCEDURE: Self-reported height/weight, hypothyroidism, and
      pregnancy/live birth were determined among acute lymphoblastic and myeloid
      leukemia survivors (n = 3,467) participating in the Childhood Cancer Survivor
      Study, an ongoing cohort study of 5-year survivors of pediatric cancers diagnosed
      from 1970 to 1986. RESULTS: Compared with no radiotherapy, risk estimates were
      consistent across outcomes (adult short stature, hypothyroidism, absence of
      pregnancy/live birth) with CRT treatment associated with 2-3-fold increased
      risks, TBI associated with 5-10 fold increased risks, and CRT + TBI associated
      with >10 fold increased risks. Exposure to any SRT further increased risk of
      these outcomes 2-3-fold. Changes in body composition were more nuanced as CRT
      only was associated with an increased risk of being overweight/obese (OR 1.6, 95%
      CI 1.3-1.9) whereas TBI only was associated with an increased risk of being
      underweight (OR 6.0, 95% CI 2.4-14.9). CONCLUSIONS: Although patients treated
      with CRT + TBI were at greatest risk for short stature, hypothyroidism, and a
      reduced likelihood of pregnancy/live birth, those treated with either modality
      alone had significantly increased risks as well, including altered body
      composition. Any SRT exposure further increased risk in an independent fashion.

PMID- 22628202
TI  - In vitro and in vivo aldose reductase inhibitory activity of standardized
      extracts and the major constituent of Andrographis paniculata.
AB  - Aldose reductase is the first enzyme in the polyol pathway and catalyzes the
      reduction of glucose to sorbitol by coupling with the oxidation of NADPH to
      NADP(+) . This sorbitol accumulation leads to various diabetic complications,
      including neuropathy, nephropathy, cataracts, and retinopathy. In the present
      study, aldose reductase inhibitory (ARI) activity of the methanolic as well as
      standardized extracts of Andrographis paniculata (Burm. f.) Wall. ex Nees
      (Acanthaceae) and its chief constituent, andrographolide, were studied using in
      vitro and in vivo methods. In the in vitro method, rat lens as well as kidney
      homogenates were used for the preparation of enzyme, whereas the effect of these
      test samples on the galactitol level in the eye lens was studied in a
      galactosemic rat model in vivo. The results of the study revealed that both
      extracts of the plant and its major compound, andrographolide, possess ARI
      activity in vitro. They were also found to significantly decrease galactitol
      accumulation in vivo.

PMID- 22628203
TI  - Is there empirical evidence for decreasing returns to scale in a health capital
      model?
AB  - We estimate a health investment equation, derived from a health capital model
      that is an extension of the well-known Grossman model. Of particular interest is
      whether the health production function has constant returns to scale, as in the
      standard Grossman model, or decreasing returns to scale, as in the Ehrlich-Chuma
      model and extensions thereof. The model with decreasing returns to scale has a
      number of theoretically and empirically desirable characteristics that the
      constant returns model does not have. Although our empirical equation does not
      point-identify the decreasing returns to scale curvature parameter, it does allow
      us to test for constant versus decreasing returns to scale. The results are
      suggestive of decreasing returns and in line with prior estimates from the
      literature. But when we attempt to control for the endogeneity of health by using
      instrumental variables, the results become inconclusive. This brings into
      question the robustness of prior estimates in this literature.

PMID- 22628204
TI  - Assessment of molecular interactions through magnetic relaxation.

PMID- 22628205
TI  - Protective effects of topical application of a poorly soluble antioxidant
      astaxanthin liposomal formulation on ultraviolet-induced skin damage.
AB  - Astaxanthin (Asx) would be expected to prevent ultraviolet (UV)-induced skin
      damage, as it is regarded as a potent antioxidative carotenoid in biological
      membranes. However, it is difficult to administer Asx topically to skin because
      of its poor water solubility. In this study, we attempted to solve this problem
      by preparing liposomes containing Asx (Asx-lipo), which were dispersible in the
      water phase, and therefore, suitable for topical application to the skin. Asx
      lipo was shown to have potent scavenging ability against chemiluminescence
      dependent singlet oxygen production in the water phase. When Asx-lipo was applied
      to skin before UV exposure, UV-induced skin thickening was prevented.
      Interestingly, collagen reduction induced by UV exposure was also prevented by
      preadministration of Asx-lipo. In addition, topical administration of Asx-lipo
      containing cationic lipid inhibited melanin production in skin exposed to UV.
      Consequently, we succeeded in preventing UV-induced skin damage using a topical
      application of a liposomal formulation containing Asx.

PMID- 22628206
TI  - Corneal topographic analysis by 3-dimensional anterior segment optical coherence
      tomography after endothelial keratoplasty.
AB  - PURPOSE: To investigate the characteristics of the corneal topography with three
      dimensional (3-D) anterior segment optical coherence tomography (AS-OCT)
      following Descemet's stripping automated endothelial keratoplasty (DSAEK).
      METHODS: Thirty-four eyes of 33 patients following DSAEK were studied. In
      addition to conventional topographic maps, the elevation map of the intrastromal
      interface and pachymetric maps of the host and graft were obtained by corneal
      topographic analysis using 3-D AS-OCT. The coefficient of variation of the
      corneal power (CV-Pa, CV-Pp) and root mean squares of the corneal elevation (RMS
      Ea, RMS-Ep) of the anterior and posterior corneal surfaces were determined. Based
      on the combination of the regularity and irregularity of the anterior and
      posterior surfaces, subjects were classified into four types: type 1,
      regular/regular; type 2, irregular/regular; type 3, regular/irregular; and type
      4, irregular/irregular. RESULTS: The average graft decentration was 0.59 +/- 0.23
      mm. The proportion of types 1, 2, 3, and 4 were 59%, 9%, 24%, and 9 %,
      respectively. The CV-Pa (25.8 +/- 8.9) and CV-Pp (-73.9 +/- 18.0) of the type 1
      corneas were significantly better than that of type 2 and type 3 corneas,
      respectively. The RMS-Ea (5.1 +/- 1.3) and RMS-Ep (26.0 +/- 7.3) of the type 1
      corneas were significantly better than that of type 2 and type 3 corneas.
      CONCLUSIONS: An OCT-based corneal topographer might be useful in determining the
      factors associated with optical quality of the cornea following DSAEK by
      analyzing the topographic characteristics of host and donor separately.

PMID- 22628207
TI  - Eye size in threshold retinopathy of prematurity, based on a Danish preterm
      infant series: early axial eye growth, pre- and postnatal aspects.
AB  - PURPOSE: To validate a hypothesis of restricted postnatal ocular growth
      associated with advanced retinopathy of prematurity (ROP), with a view also to
      preceding intrauterine growth retardation. METHODS: A clinically uniform sample
      of 28 preterm neonates was examined under general anesthesia from 1997 to 2002
      for threshold retinopathy of prematurity (T-ROP), axial ultrasound oculometry
      being part of the evaluation (valid data in 53 eyes). Median values for
      gestational age at delivery (GA) and birth weight (BW) 27 weeks and 855 g,
      respectively, ranges 24.7-30.9 weeks and 480-1594 g. Median postconceptional age
      (PCA) at exam was 36.2 weeks (32.2-41.4 weeks) and median postnatal age was 9
      weeks (5.8-14 weeks). "Small for gestational age" (SGA) at delivery was given by
      an individual birth weight standard deviation score. RESULTS: Compared with a
      previous Danish preterm series with less ROP, age-adjusted axial lengths (AL) in
      the T-ROP eyes were roughly 1 mm shorter and anterior chambers shallower. A
      higher GA was found to coincide with lower AL values; this appeared due to a
      subpopulation of infants loaded by SGA. The literature has no other uniform
      oculometry series of preterms of a similar advanced ROP degree. The present
      Danish results add to the composite picture drawn by neonatal reports from other
      investigators. CONCLUSIONS: There is evidence of postnatal ocular growth
      restriction in preterms associated with severe ROP. Some kind of latency is
      probable, from the immediate delivery-related biological effects until the
      appearance of macroscopic evidence. Statistics further suggested SGA as an
      apparently independent prenatal predictor of subsequent ocular growth
      restriction.

PMID- 22628208
TI  - Pharmacokinetic analysis of melphalan after superselective ophthalmic artery
      infusion in preclinical models and retinoblastoma patients.
AB  - PURPOSE: To characterize melphalan pharmacokinetics after superselective
      ophthalmic artery infusion (SSOAI) in animals and children with retinoblastoma.
      METHODS: Vitreous and plasma samples of five Landrace pigs were obtained over a 4
      hour period after SSOAI of melphalan (7 mg). Melphalan cytotoxicity was evaluated
      in retinoblastoma cell lines with and without topotecan. Plasma samples were
      obtained from 17 retinoblastoma patients after SSOAI of 3 to 6 mg of melphalan to
      one (n=14) or two eyes (n=3). Correlation between plasma pharmacokinetics and
      age, dosage, and systemic toxicity was studied in patients. RESULTS: In animals,
      melphalan peak vitreous levels were greater than its IC50 and resulted in 3-fold
      vitreous-to-plasma exposure. In patients, a large variability in pharmacokinetic
      parameters was observed and it was explained mainly by body weight (P<0.05). A
      significantly higher systemic area under the curve was obtained in children
      receiving more than 0.48 mg/kg for bilateral tandem infusions (P<0.05). These
      children had 50% probability of grades 3-4 neutropenia. Plasma concentrations
      after 2 and 4 hours of SSOAI were significantly higher in these children
      (P<0.05). A synergistic cytotoxic effect of melphalan and topotecan was evident
      in cell lines. CONCLUSIONS: Potentially active levels of melphalan after SSOAI
      were achieved in the vitreous of animals. Low systemic exposure was found in
      animals and children. Doses greater than 0.48 mg/kg, given for bilateral tandem
      infusions, were associated with significantly higher plasma levels and increased
      risk of neutropenia. Synergistic in vitro cytotoxicity between melphalan and
      topotecan favors combination treatment.

PMID- 22628209
TI  - New crosslinkers for electrospun chitosan fibre mats. I. Chemical analysis.
AB  - Chitosan (CS), the deacetylated form of chitin, the second most abundant, natural
      polysaccharide, is attractive for applications in the biomedical field because of
      its biocompatibility and resorption rates, which are higher than chitin.
      Crosslinking improves chemical and mechanical stability of CS. Here, we report
      the successful utilization of a new set of crosslinkers for electrospun CS.
      Genipin, hexamethylene-1,6-diaminocarboxysulphonate (HDACS) and epichlorohydrin
      (ECH) have not been previously explored for crosslinking of electrospun CS. In
      this first part of a two-part publication, we report the morphology, determined
      by field emission scanning electron microscopy (FESEM), and chemical
      interactions, determined by Fourier transform infrared microscopy, respectively.
      FESEM revealed that CS could successfully be electrospun from trifluoroacetic
      acid with genipin, HDACS and ECH added to the solution. Diameters were 267 +/-
      199 nm, 644 +/- 359 nm and 896 +/- 435 nm for CS-genipin, CS-HDACS and CS-ECH,
      respectively. Short- (15 min) and long-term (72 h) dissolution tests (T(600))
      were performed in acidic, neutral and basic pHs (3, 7 and 12). Post-spinning
      activation by heat and base to enhance crosslinking of CS-HDACS and CS-ECH
      decreased the fibre diameters and improved the stability. In the second part of
      this publication, we report the mechanical properties of the fibres.

PMID- 22628210
TI  - Metabolomics: a valuable tool for stem cell monitoring in regenerative medicine.
AB  - Metabolomics is a method for investigation of changes in the global metabolite
      profile of cells. This paper discusses the technical application of the approach,
      considering metabolite extraction, separation, mass spectrometry and data
      interpretation. A particular focus is on the application of metabolomics to the
      study of stem cell physiology in the context of biomaterials and regenerative
      medicine. Case studies are used to illustrate key points, focusing on the use of
      metabolomics in the examination of mesenchymal stem cell responses to titania
      nanopillared substrata designed for orthopaedic applications.

PMID- 22628211
TI  - Function suggests nano-structure: electrophysiology supports that granule
      membranes play dice.
AB  - Cellular communication depends on membrane fusion mechanisms. SNARE proteins play
      a fundamental role in all intracellular fusion reactions associated with the life
      cycle of secretory vesicles, such as vesicle-vesicle and vesicle plasma membrane
      fusion at the porosome base in the cell plasma membrane. We present growth and
      elimination (G&E), a birth and death model for the investigation of granule
      growth, its evoked and spontaneous secretion and their information content. Using
      a statistical mechanics approach in which SNARE components are viewed as
      interacting particles, the G&E model provides a simple 'nano-machine' of SNARE
      self-aggregation behind granule growth and secretion. Results from experimental
      work, mathematical calculations and statistical modelling suggest that for
      vesicle growth a minimal aggregation of three SNAREs is required, while for the
      evoked secretion one SNARE is enough. Furthermore, the required number of SNARE
      aggregates (which varies between cell types and is nearly proportional to the
      square root of the mean granule diameter) affects and is statistically
      identifiable from the size distributions of spontaneous and evoked secreted
      granules. The new statistical mechanics approach to granule fusion is bound to
      have a significant changing effect on the investigation of the pathophysiology of
      secretory mechanisms and methodologies for the investigation of secretion.

PMID- 22628212
TI  - Reconstructing the flight kinematics of swarming and mating in wild mosquitoes.
AB  - We describe a novel tracking system for reconstructing three-dimensional tracks
      of individual mosquitoes in wild swarms and present the results of validating the
      system by filming swarms and mating events of the malaria mosquito Anopheles
      gambiae in Mali. The tracking system is designed to address noisy, low frame-rate
      (25 frames per second) video streams from a stereo camera system. Because flying
      A. gambiae move at 1-4 m s(-1), they appear as faded streaks in the images or
      sometimes do not appear at all. We provide an adaptive algorithm to search for
      missing streaks and a likelihood function that uses streak endpoints to extract
      velocity information. A modified multi-hypothesis tracker probabilistically
      addresses occlusions and a particle filter estimates the trajectories. The output
      of the tracking algorithm is a set of track segments with an average length of
      0.6-1 s. The segments are verified and combined under human supervision to create
      individual tracks up to the duration of the video (90 s). We evaluate tracking
      performance using an established metric for multi-target tracking and validate
      the accuracy using independent stereo measurements of a single swarm. Three
      dimensional reconstructions of A. gambiae swarming and mating events are
      presented.

PMID- 22628213
TI  - Post-secretion processing influences spider silk performance.
AB  - Phenotypic variation facilitates adaptations to novel environments. Silk is an
      example of a highly variable biomaterial. The two-spidroin (MaSp) model suggests
      that spider major ampullate (MA) silk is composed of two proteins-MaSp1
      predominately contains alanine and glycine and forms strength enhancing beta
      sheet crystals, while MaSp2 contains proline and forms elastic spirals.
      Nonetheless, mechanical properties can vary in spider silks without congruent
      amino acid compositional changes. We predicted that post-secretion processing
      causes variation in the mechanical performance of wild MA silk independent of
      protein composition or spinning speed across 10 species of spider. We used
      supercontraction to remove post-secretion effects and compared the mechanics of
      silk in this 'ground state' with wild native silks. Native silk mechanics varied
      less among species compared with 'ground state' silks. Variability in the
      mechanics of 'ground state' silks was associated with proline composition.
      However, variability in native silks did not. We attribute interspecific
      similarities in the mechanical properties of native silks, regardless of amino
      acid compositions, to glandular processes altering molecular alignment of the
      proteins prior to extrusion. Such post-secretion processing may enable MA silk to
      maintain functionality across environments, facilitating its function as a
      component of an insect-catching web.

PMID- 22628214
TI  - The sensitivity of human mesenchymal stem cells to vibration and cold storage
      conditions representative of cold transportation.
AB  - In the current study, the mechanical and hypothermic damage induced by vibration
      and cold storage on human mesenchymal stem cells (hMSCs) stored at 2-8 degrees C
      was quantified by measuring the total cell number and cell viability after
      exposure to vibration at 50 Hz (peak acceleration 140 m s(-2) and peak
      displacement 1.4 mm), 25 Hz (peak acceleration 140 m s(-2), peak displacement 5.7
      mm), 10 Hz (peak acceleration 20 m s(-2), peak displacement 5.1 mm) and cold
      storage for several durations. To quantify the viability of the cells, in
      addition to the trypan blue exclusion method, the combination of annexin V-FITC
      and propidium iodide was applied to understand the mode of cell death. Cell
      granularity and a panel of cell surface markers for stemness, including CD29,
      CD44, CD105 and CD166, were also evaluated for each condition. It was found that
      hMSCs were sensitive to vibration at 25 Hz, with moderate effects at 50 Hz and no
      effects at 10 Hz. Vibration at 25 Hz also increased CD29 and CD44 expression. The
      study further showed that cold storage alone caused a decrease in cell viability,
      especially after 48 h, and also increased CD29 and CD44 and attenuated CD105
      expressions. Cell death would most likely be the consequence of membrane rupture,
      owing to necrosis induced by cold storage. The sensitivity of cells to different
      vibrations within the mechanical system is due to a combined effect of
      displacement and acceleration, and hMSCs with a longer cold storage duration were
      more susceptible to vibration damage, indicating a coupling between the effects
      of vibration and cold storage.

PMID- 22628215
TI  - The optimal deployment of synergistic antibiotics: a control-theoretic approach.
AB  - Medical and pharmacological communities have long searched for antimicrobial
      drugs that increase their effect when used in combination, an interaction known
      as synergism. These drug combinations, however, impose selective pressures in
      favour of multi-drug resistance and as a result, the benefit of synergy may be
      lost after only a few bacterial generations. Furthermore, there is experimental
      evidence that antibiotic treatment can disrupt colonization resistance by
      shifting the balance between enteropathogenic and commensal bacteria in favour of
      the pathogens, with the potential to increase the risk of infections. So, we ask,
      what is the best way of using synergistic drugs? We pose an evolutionary model of
      commensal and pathogenic bacteria competing in a continuous culture device for a
      single limiting carbon source under the effect of two bacteriostatic and
      synergistic antibiotics. This model allows us to evaluate the efficacy of
      different drug deployment strategies and, using ideas from optimal control
      theory, to understand whether there are circumstances in which other types of
      therapy might be favoured over those based on fixed-dose multi-drug combinations.
      Our main result can be stated thus: the optimal deployment of synergistic
      antibiotics to remove a pathogen in the presence of commensal bacteria in our
      model system occurs not in combination, but by deploying them sequentially.

PMID- 22628217
TI  - Homozygous survival motor neuron 2 gene deletion and sporadic lower motor neuron
      disease in children: case report and literature review.
AB  - A case of lower motor neuron disease with homozygous survival motor neuron 2
      (SMN2) gene deletion is reported in this article. A 7-year-old boy was admitted
      to our hospital with main complaints of lower extremity weakness and difficulty
      squatting for the past year. SMN gene copies were quantified by multiplex
      ligation-dependent probe amplification. Exons 7 and 8 of the SMN1 gene were
      normal, but homozygous deletion of exons 7 and 8 of the SMN2 gene was identified.
      Homozygous deletion of exons 7 and 8 of the SMN centromeric gene was detected,
      and exons 7 and 8 of the SMN1 gene were found to be normal in the proband. Two
      copies of exons 7 and 8 of the SMN1 gene were identified, and zero copies of
      exons 7 and 8 of the SMN2 gene were found. We consider that this case represents
      a previously unrecognized type of lower motor neuron disease that resulted from
      homozygous deletion of the SMN2 gene.

PMID- 22628216
TI  - Mechanical state, material properties and continuous description of an epithelial
      tissue.
AB  - During development, epithelial tissues undergo extensive morphogenesis based on
      coordinated changes of cell shape and position over time. Continuum mechanics
      describes tissue mechanical state and shape changes in terms of strain and
      stress. It accounts for individual cell properties using only a few spatially
      averaged material parameters. To determine the mechanical state and parameters in
      the Drosophila pupa dorsal thorax epithelium, we severed in vivo the adherens
      junctions around a disc-shaped domain comprising typically a hundred cells. This
      enabled a direct measurement of the strain along different orientations at once.
      The amplitude and the anisotropy of the strain increased during development. We
      also measured the stress-to-viscosity ratio and similarly found an increase in
      amplitude and anisotropy. The relaxation time was of the order of 10 s. We
      propose a space-time, continuous model of the relaxation. Good agreement with
      experimental data validates the description of the epithelial domain as a
      continuous, linear, visco-elastic material. We discuss the relevant time and
      length scales. Another material parameter, the ratio of external friction to
      internal viscosity, is estimated by fitting the initial velocity profile.
      Together, our results contribute to quantify forces and displacements, and their
      time evolution, during morphogenesis.

PMID- 22628218
TI  - Neonates with seizures: what predicts development?
AB  - Animal and human studies indicate that neonatal seizures are detrimental to the
      developing nervous system. This study addressed whether parameters of seizure
      severity and treatment were predictive of outcome and influenced the incidence of
      epilepsy. The outcome of babies with neonatal seizures was assessed based on
      follow-up examination, record review, and school performance. Epilepsy was
      assessed relative to developmental outcome and imaging abnormalities. There was
      no association between response to therapy and outcome. Neonates with mild or
      moderate seizure severity and decreasing severity over time, prior to
      anticonvulsant treatment, were more likely to have normal or moderately abnormal
      development than a severe outcome or death. Babies who had the highest seizure
      severity following treatment were more likely to have adverse outcomes. Those
      with normal imaging studies were more likely to have better outcome than those
      with diffuse severe abnormalities. Children with epilepsy were more likely to
      have abnormal development and imaging.

PMID- 22628219
TI  - Seizures as the clinical presenting symptom in children with brain tumors.
AB  - This study summarizes our clinical and surgical experience with pediatric brain
      tumors that were initially presented with seizures. The records of 367
      consecutive children, treated for brain tumors between the years 1996 and 2007,
      were retrospectively analyzed, focusing on the clinical manifestations,
      diagnostic gap, and postoperative seizure follow-up that lasted at least 2 years.
      Seizures, mainly focal, were the clinical manifestation of brain tumor in 57 of
      367 children. Normal neurologic examination and electroencephalography (EEG) were
      in 77.8% and 37.5%, respectively. Diagnostic gap correlated with low-grade and
      temporal lobe tumors. Postoperative follow-up revealed freedom of seizure in
      77.6%. Favorable seizure outcome correlated with low preoperative seizures
      frequency, preoperative response to antiepileptic drugs, and hemispheric tumor
      location. We conclude that response to antiepileptic drugs, generalized seizures,
      normal EEG, and normal neurologic examination should not exclude tumor etiology.
      Moreover, broader indications for imaging should be employed while evaluating a
      child with a seizure.

PMID- 22628220
TI  - Pilot study on executive function and adaptive skills in adolescents and young
      adults with mitochondrial disease.
AB  - High-functioning adolescents and young adults with mitochondrial disease are now
      attempting transitions to postsecondary environments. This pilot and case study
      explores factors that interfere with their successful transition through behavior
      rating scales addressing academic skills and behavior. In the Behavior Assessment
      System for Children, Second Edition, Spearman correlation matrices showed that
      students' attitude to school was associated with depression and anxiety. Mothers'
      reports linked internalizing disorders with somatic symptoms. Two case studies,
      with Behavior Rating Inventory of Executive Function profiles, show the role
      executive functions play in academic success. Attention to both cognitive and
      psychiatric concerns may increase success in academics and enhance the sense of
      well-being in older students with mitochondrial disease.

PMID- 22628221
TI  - Durable immune response to inactivated H1N1 vaccine is less likely in children
      with sickle cell anemia receiving chronic transfusions.
AB  - BACKGROUND: Defects in the immune system may affect vaccine responsiveness.
      Because of the splenic hypofunction and abnormal opsonic activity, it was unknown
      whether patients with sickle cell disease (SCD) would respond appropriately to
      H1N1 vaccination. The objective of this study was to assess seroprotective post
      vaccine H1N1 antibody response in children with SCD. PROCEDURE: Serum antibody
      titers were measured by hemagglutination inhibition and microneutralization (MN)
      assays. Correlations were established between clinical and treatment parameters
      and immune response. RESULTS: Twenty-nine of 38 (76.3%) subjects (mean age 11 +/-
      5.4 years) had durable protective antibody titers 8 +/- 1.6 months (range 5-12
      months) post-vaccination. Lessened immune response was not associated with time
      interval from vaccination, splenectomy, or hydroxyurea treatment. Lack of
      antibody response was associated with age less than 3 years and treatment with
      chronic transfusions. Of the nine non-responders, seven were on chronic
      transfusions (39% unresponsiveness rate in the transfused group). The difference
      in the number of patients with seropositivity between the non-transfused and the
      transfused groups was statistically significant (P = 0.039). CONCLUSIONS: Most
      subjects were able to mount an influenza-specific antibody response against the
      inactivated H1N1 vaccine. Similar to the general population, children less than 3
      years were less likely to respond. In addition, patients on chronic transfusions
      were less likely to respond when compared to non-transfused children. Clinicians
      should be aware of the possibility of decreased vaccine response in patients with
      SCD on chronic transfusions. We postulate that transfusion-related
      immunomodulation (TRIM) may be related to decreased response.

PMID- 22628222
TI  - Hepatoprotection of berberine against hydrogen peroxide-induced apoptosis by
      upregulation of Sirtuin 1.
AB  - Berberine (BBR) has been suggested to be a hepatoprotective agent for oxidative
      stress-related liver diseases because of its antioxidant activity. However, the
      antioxidant mechanisms of BBR are still not fully understood. In the present
      study, the protective effect of BBR was evaluated, and the underlying molecular
      mechanisms were investigated in hepatic cell line L02. Results from cell
      viability and apoptosis assay showed that in cells exposed to hydrogen peroxide
      (H2 O2 ), the pretreatment of 12 MUM BBR could increase cell viability by 19.10
      +/- 7.40% and reduce apoptotic cells by 7.91 +/- 0.78%. A significant change in
      the expression levels of sirtuin 1 (SIRT1) and apoptosis-related proteins was
      also observed in the BBR-pretreated hepatocytes under exposure to H2 O2 .
      Furthermore, BBR exhibited a time-dependent effect on upregulation of SIRT1 in
      L02 cells. This study demonstrated that the protective effect of BBR against H2
      O2 -induced apoptosis was associated with regulation of SIRT1 in hepatic cell
      line L02, which provided a possible explanation for its antioxidant activity, and
      implied an application of BBR for the therapeutic relevance in oxidative-stress
      related liver diseases.

PMID- 22628223
TI  - Epigenetic modulation by TFII-I during embryonic stem cell differentiation.
AB  - TFII-I transcription factors play an essential role during early vertebrate
      embryogenesis. Genome-wide mapping studies by ChIP-seq and ChIP-chip revealed
      that TFII-I primes multiple genomic loci in mouse embryonic stem cells and
      embryonic tissues. Moreover, many TFII-I-bound regions co-localize with
      H3K4me3/K27me3 bivalent chromatin within the promoters of lineage-specific genes.
      This minireview provides a summary of current knowledge regarding the function of
      TFII-I in epigenetic control of stem cell differentiation.

PMID- 22628225
TI  - Optical and mechanical clot detection methodologies: a comparison study for
      routine coagulation testing.
AB  - BACKGROUND: Automated coagulation analyzers are preferred to meet increasing
      coagulation test volume. Two distinct technological families exist based on
      optical and mechanical clot detection methodologies. Which one is superior to the
      other is still a conflict and needs new studies. METHODS: We have compared
      prothrombin and activated partial thromboplastin results obtained with mechanical
      method with those obtained by photo-optical method used routinely in our
      specialized laboratory. RESULTS: The instrumental results showed good precision
      ranging between 0.7% and 1.8% coefficient of variation. Statistical analysis
      demonstrated an excellent correlation between the photo-optical and mechanical
      analyzers for PT (R2 0.97), and aPTT (R2 0.85). CONCLUSION: Correlation between
      the two clot-detection systems was maintained even when measuring turbid samples
      (R2 >= 0.97 for two tests).

PMID- 22628224
TI  - Cholinergic-associated loss of hnRNP-A/B in Alzheimer's disease impairs cortical
      splicing and cognitive function in mice.
AB  - Genetic studies link inherited errors in RNA metabolism to familial
      neurodegenerative disease. Here, we report such errors and the underlying
      mechanism in sporadic Alzheimer's disease (AD). AD entorhinal cortices presented
      globally impaired exon exclusions and selective loss of the hnRNP A/B splicing
      factors. Supporting functional relevance, hnRNP A/B knockdown induced alternative
      splicing impairments and dendrite loss in primary neurons, and memory and
      electrocorticographic impairments in mice. Transgenic mice with disease
      associated mutations in APP or Tau displayed no alterations in hnRNP A/B
      suggesting that its loss in AD is independent of Abeta and Tau toxicity. However,
      cholinergic excitation increased hnRNP A/B levels while in vivo neurotoxin
      mediated destruction of cholinergic neurons caused cortical AD-like decrease in
      hnRNP A/B and recapitulated the alternative splicing pattern of AD patients. Our
      findings present cholinergic-mediated hnRNP A/B loss and impaired RNA metabolism
      as important mechanisms involved in AD.

PMID- 22628226
TI  - Evaluation of two enzyme immunoassays for the detection of the cocaine metabolite
      benzoylecgonine in 1,398 urine specimens.
AB  - BACKGROUND: Benzoylecgonine (BE) is the primary urinary metabolite of cocaine.
      Two enzyme immunoassays were evaluated for the detection of BEin urine with a 300
      ng/ml cutoff: the DRI(r) Cocaine Metabolite Assay and Lin-Zhi International's
      (LZ) Cocaine Metabolite Enzyme Immunoassay. METHODS: This study involved 1,398
      urine specimens from criminal justice and pain management programs. Gas
      chromatography/mass spectrometry (GC/MS) data were obtained for presumptive
      positives, and for negative urine specimens yielding responses significantly
      above the negative control. RESULTS: Approximately 46% (644) of the specimens
      yielded positive results by DRI, and 47% (664) were positive by LZ. One specimen
      screened positive with both assays but was found to have a nondetectable BE
      concentration by GC/MS, indicating one false positive for each assay. Twenty-one
      specimens yielding negative DRIresults contained BEabove 300 ng/ml, and 29
      specimens yielded false negatives with the LZassay. Therefore, the overall
      agreement between both immunoassays and GC/MSresults was 98%. Assay sensitivity
      was 0.968 (DRI) and 0.958 (LZ); the selectivity for both assays was 0.999. Urine
      specimens containing cocaine, additional cocaine metabolites, and other drugs
      were also tested. No cross-reactivity was observed. CONCLUSION: Both the DRIand
      LZassays provide a precise, reliable method for the routine detection of BEin
      urine.

PMID- 22628227
TI  - Significant association of elevated concentration of plasma YKL-40 with disease
      severity in patients with pelvic inflammatory disease.
AB  - INTRODUCTION: To date, no study reports the implication of YKL-40 in pelvic
      inflammatory disease (PID). Therefore, we investigate the levels of plasma YKL-40
      in patients with PID and further associate its expression with the severity of
      disease. METHODS: We designed a hospital-based case-control study with
      approximate 1:1 ratio and consecutively recruited 64 patients with PID and 70
      control women. We collected blood samples from 64 women with PID before and after
      they received treatment and 70 control women to detect levels of plasma YKL-40
      and C-reactive protein (CRP) as well as white blood cell and neutrophil counts.
      RESULTS: The results revealed that levels of plasma YKL-40 were significantly
      elevated in patients with PID as compared to those in controls (38.36 vs. 21.69
      ng/ml, P = 0.001) but the significant difference was restricted to women aged 30
      years or old after age stratification (56.75 vs. 23.61 ng/ml, P <= 0.001). It
      declined significantly after they received treatment (median: 38.36 vs. 27.54
      ng/ml; P <= 0.001). Although both plasma YKL-40 and CRP were elevated in patients
      with tubo-ovarian abscess, PID patients with surgery exhibited higher YKL-40
      concentration than those without surgery (median: 82.05 vs. 30.19 ng/ml, P =
      0.005) and only plasma YKL-40 was significantly associated with the length of the
      hospital stay (P <= 0.001, R = 0.604). CONCLUSION: We conclude that once
      individuals are diagnosed to have PID, YKL-40 may act as a biomarker to predict
      the severity and clinical outcome of the disease.

PMID- 22628228
TI  - Clinically insignificant negative interferences of spironolactone, potassium
      canrenoate, and their common metabolite canrenone in new dimension vista LOCI
      digoxin immunoassay.
AB  - Spironolactone, a potassium-sparing diuretic metabolized to canrenone is often
      used with digoxin to treat various conditions including congestive heart failure.
      Potassium canrenoate is a similar drug, which is also metabolized to canrenone.
      Due to reported both positive and negative interference of spironolactone,
      potassium canrenoate, and their common metabolite canrenone with digoxin
      immunoassays, we investigated potential interference of these compounds with the
      new homogenous sequential chemiluminescent assay for digoxin based on the
      luminescent oxygen channeling technology (LOCI digoxin) for application on the
      Dimension and Vista platform. When aliquots of a drug-free serum pool were
      supplemented with various amounts of spironolactone, potassium canrenoate, or
      canrenone and apparent digoxin values were measured using Dimension Vista LOCI
      digoxin assay, we observed no detected value except when aliquots were
      supplemented with very high amounts of potassium canrenoate or canrenone.
      However, we observed that apparent digoxin concentrations were very low. When
      aliquots of a serum digoxin pool (prepared by pooling specimens from patients
      receiving digoxin), were further supplemented with various amounts of
      spironolactone, potassium canrenoate, or canrenone and serum digoxin
      concentrations were remeasured using the LOCIdigoxin assay, only statistically
      significant falsely lower digoxin values (negative interference) were observed in
      specimens containing very high amounts of canrenone or potassium canrenoate.
      However, such small bias may not have any clinical significance. We conclude that
      new Dimension Vista LOCI digoxin assay is virtually free from interferences of
      spironolactone, potassium canrenoate, and their common metabolite canrenone.

PMID- 22628229
TI  - Identification of novel low molecular weight serum peptidome biomarkers for non
      small cell lung cancer (NSCLC).
AB  - AIM: To identify discriminating protein patterns in serum samples among non-small
      cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD),
      pneumonia, and healthy controls. To discover specific low molecular weight (LMW)
      serum peptidome biomarkers and establish a diagnostic pattern for NSCLCby using
      proteomic technology. METHODS: We used magnetic bead-based separation followed by
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) to identify patients with NSCLC, COPD, and pneumonia. A total of
      154 serum samples were analyzed in this study, among which there were 60 serum
      samples from NSCLC patients, 30 from patients with other lung-related diseases
      (16 pneumonia patients and 14 patients with COPD) as disease controls, and 64
      from healthy volunteers as healthy control. The mass spectra, analyzed using
      ClinProTools software, distinguished between cancer patients and healthy
      individuals based on GA algorithm model. RESULTS: In this study, we generated
      numerous discriminating m/z peaks as well as disease-specific discrimination
      peaks. A set of five potential biomarkers (m/z: 7,763.24, 1,012.61, 4,153.16,
      1,450.55, and 2,878.89) could be used as the diagnostic biomarkers to distinguish
      NSCLCpatients from healthy controls. In the training set, patients with NSCLC
      could be identified with sensitivity of 97.5% and specificity of 98.8%. Similar
      results were obtained in the testing set, showing 80.7% sensitivity and 91.2%
      specificity. CONCLUSION: Our study demonstrated that a combined application of
      magnetic beads with MALDI-TOF MS technique was suitable for identification of
      serum biomarkers for NSCLC.

PMID- 22628230
TI  - Serum lipid hydroperoxide levels and paraoxonase activity in patients with lung,
      breast, and colorectal cancer.
AB  - OBJECTIVES: The objectives of this article are to investigate the serum lipid
      hydroperoxide (LOOH) levels and paraoxonase-1 (PON1) and arylesterase (ARE)
      activity in patients with lung, breast, and colorectal cancer. DESIGN AND
      METHODS: Serum PON1 and ARE activities and LOOH levels were measured in 110
      patients with cancer and same number of age- and sex-matched controls. RESULTS:
      Serum LOOH levels were found to be increased while serum PON1 and ARE activities
      were found to be decreased in patients compared to controls. PON1 activity was
      found to be lower in patients with breast cancer than in patients with lung and
      colorectal cancer. There were positive correlations between the serum PON1 and
      ARE activities in patients with colorectal cancer. CONCLUSION: We concluded that
      decreased PON1 and ARE activities and increased LOOH levels might have a
      connection to carcinogenesis. PON1 activity is decreased in all patients but it
      does not seem to be related to metastase status except for colorectal cancer.

PMID- 22628231
TI  - Oxidative status and DNA damage in chidren with marasmic malnutrition.
AB  - Malnutrition as a lack of several substances containing antioxidants such as
      vitamins and micronutrients, while showing a predisposition for lipid
      peroxidation and DNA damage, is also characterized by a slowing down of the
      metabolic processes, which may then have protective properties against DNA damage
      due to a reduction in endogenous free radical production. This study aimed to
      examine the oxidative status and DNA damage in cases of marasmus. The study
      comprised 28 infants aged 6-24 months with marasmus only and 28 age-matched
      healthy infants. DNA damage was examined by the alkali single cell
      electrophoresis method (Comet assay) on mononuclear leukocytes. The total oxidant
      status (TOS) and total antioxidant status (TAS) were measured by colormetric auto
      analyzer and the oxidative stress index (OSI) was calculated. The TOS, TAS, and
      OSI levels of the patient group were found to be significantly lower compared to
      the control group (P < 0.01, P < 0.01, P < 0.01, respectively). No statistically
      significant difference was found between the two groups in terms of mononuclear
      leukocyte DNA damage (P > 0.05). The findings of this study showed that in
      marasmus cases, the oxidative and antioxidative processes, which have a
      counteractive effect, decreased together. The other results of the study indicate
      that there is no increase in DNA damage in marasmus cases.

PMID- 22628232
TI  - Factor V Leiden, prothrombin 20210G>A, MTHFR 677C>T and 1298A>C, and
      homocysteinemia in Tunisian blood donors.
AB  - Specific genetic conditions are known to be associated with high risk of venous
      thromboembolism. This genetic basis varies widely between ethnic groups. We
      investigated the distribution of four inherited polymorphisms in 113 unselected
      Tunisian blood donors by using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) method. The allele frequencies of Factor V Leiden
      (FVL), prothrombin 20210G>A, methylenetetrahydrofolate reductase (MTHFR) 677C>T,
      and MTHFR 1298A>C mutations were 3, 0.9, 30, and 31%, respectively. The MTHFR
      677C>T polymorphism was influenced by age. Twenty-nine of the 113 blood donors
      demonstrated more than one genetic markers. Hyperhomocysteinemia was found in 12
      subjects, and it was statistically associated to the MTHFR 677TT genotype.
      Principal component analysis allowed disclosing the resemblance between
      Mediterranean populations. Our findings may be helpful for population genetics
      study, and provide epidemiologic database for further studies in thrombosis field
      among Tunisians.

PMID- 22628233
TI  - New sandwich-type enzyme-linked immunosorbent assay for human MxA protein in a
      whole blood using monoclonal antibodies against GTP-binding domain for
      recognition of viral infection.
AB  - OBJECTIVES: To develop a clinically significant and practical enzyme-linked
      immunosorbent assay (ELISA) for the detection of MxA protein in human whole
      blood, a biological marker of viral infection. DESIGN AND METHODS: A sandwich
      ELISA suitable for the measurement of human MxA protein in whole blood was
      developed using mouse monoclonal antibodies (mAbs) raised against the GTP-binding
      domain of human MxA protein. Prior to the assay, the whole blood sample was
      treated with special buffer to extract the MxA protein, improve its stability,
      and avoid interference from hemoglobin. RESULTS: This ELISA meets all the
      requirements for use in routine clinical assays, especially in terms of
      sensitivity (detection limit: 1.3 ng/ml whole blood), accuracy (recovery: 93.0
      100.0%), and rapidity (<1.5 h). The present ELISA had a sensitivity of 100% and a
      specificity of 100% for viral infection when compared to samples from healthy
      control and 87.1% and 90.9% when compared to samples from the bacterial infection
      group. CONCLUSION: We have developed a new ELISA for measuring MxA protein in
      human whole blood using mAbs specific for the GTP-binding domain of MxA. This
      ELISA has analytical performance enough for routine clinical assay and can be
      used in detecting the possibility of viral infection.

PMID- 22628234
TI  - Detection of anti-aquaporin-4 antibodies in neuromyelitis optica: comparison of
      tissue-based and cell-based indirect immunofluorescence assays and ELISA.
AB  - NMO-IgG against aquaporin-4 (AQP4) is a specific marker for neuromyelitis optica
      (NMO). We evaluated the performance of different NMO-IgG detecting methods. In
      124 sera (from 54 with NMO spectrum disorders including nine with NMO, ten with
      multiple sclerosis including two with OSMS, and 60 with other neurological
      diseases), NMO-IgG was measured with tissue-based indirect immunofluorescence
      (IIF-tissue) using mouse cerebellum, cell-based IIF (IIF-AQP4) using transfected
      HEK293 cells which express human AQP4, and AQP4 autoantibody detecting enzyme
      linked immunosorbent assay (ELISA-AQP4). The sensitivities and specificities of
      three assays were 44.4-55.6% and 87.0-92.2% for detecting NMO, and 11.1-20.4% and
      95.7-97.1% for detecting NMO spectrum disorders. Although there was no
      significant difference, the patients with NMO or NMO spectrum disorders showed
      higher rates of seropositivity in the ELISA-AQP4 vs. IIF assays. Out of the 19
      sera with NMO-IgG, in at least one test, only six (31.6%) were found to be
      positive by all three assays. Among the three methods, the ranges of co
      negativities, co-positivities, and agreement were 77.4-97.4%, 42.9-75.0%, and
      91.1-95.2% (kappa 0.475-0.641), respectively. In patients who had positive ELISA
      AQP4 results, IIF-AQP4 positivity was associated with NMO (P = 0.01). In summary,
      we observed an increased prevalence of NMO-IgG in patients with NMO and NMO
      spectrum disorders. ELISA-AQP4 may be more sensitive and specific when confirmed
      by IIF-AQP4.

PMID- 22628235
TI  - A spectrophotometric method to precisely determine endpoint titers in complement
      fixation assays.
AB  - Since the early 20th century, complement fixation (CF) testing has been used to
      quantify the humoral response to various pathogens. The qualification of a
      positive result is based on a subjective determination of 30% lysis of sheep red
      blood cells, which can lead to variability in the analysis. A spectrophotometric
      reading of a standard with a known 30% lysis was used to standardize the
      currently used CF method and tested with controls and patient sera for various
      fungal assays. By utilizing this method a precise and non-subjective
      determination of endpoint titers was achieved.

PMID- 22628236
TI  - Leukocyte cell population analysis from the coulter automatic blood cell analyzer
      DxH800 to monitor the effect of G-CSF.
AB  - BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) induces the formation
      of toxic granulation neutrophils (TGNs), which are found in many inflammatory
      responses. Cell population data (CPD) may be able to clarify the effect of G-CSF,
      and potentially help doctors in discriminating the effect of G-CSF from other
      inflammatory situations. METHODS: To achieve this, we performed analyses of
      leukocyte CPD from normal controls and healthy donors that had received G-CSF for
      peripheral blood stem cells (PBSCs) mobilization (G-CSF group). RESULTS: Two
      hundred and seventy-one subjects were enrolled as normal controls, and 21
      subjects were enrolled in the G-CSF group. Mean volume (MN-V)-neutrophils (NE),
      mean axial light loss (MN-AL2)-NE, and all standard deviation (SD) parameters
      increased significantly, whereas all light scattering parameters, mean median
      angle light scatter (MN-MALS)-NE, mean upper median angle light scatter (MN
      UMALS)-NE, mean lower median angle light scatter (MN-LMALS)-NE, and mean low
      angle light scatter (MN-LALS)-NE reduced significantly in the G-CSF group. MN-V
      lymphocytes (LY) from the G-CSF group showed no significant difference (P =
      0.143), whereas MN-V-monocytes (MO) were significantly decreased (P < 0.001).
      Receiver operating characteristic (ROC) curves for the discrimination of the G
      CSF group from normal controls showed excellent sensitivity in SD-LALS-NE (at
      30.85, sensitivity 95.2%, specificity 76.0%), MN-AL2-NE (at 134.5, sensitivity
      90.5%, specificity 83.0%), and SD-AL2-NE (at 16.4, sensitivity 95.2%, specificity
      95.2). Several CPD parameters of lymphocytes and monocytes, as well as
      neutrophils can be used as markers for determining the effect of G-CSF.
      CONCLUSION: Our data show that many CPD of leukocytes can be considered to be
      useful parameters of the effect of G-CSF.

PMID- 22628237
TI  - Distribution and effect of apo E genotype on plasma lipid and apolipoprotein
      profiles in overweight/obese and nonobese Chinese subjects.
AB  - BACKGROUND: Apolipoprotein E (apo E) polymorphism has been reported to influence
      some lipid profile abnormalities in some ethnic groups. This study was conducted
      mainly to examine the possible association of apo E polymorphism with
      overweight/obesity in a South West Chinese population. METHODS: Four hundred and
      fifty-four Han Chinese (282 overweight/obese and 172 normal weight control
      subjects) in Chengdu area were studied using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The
      genotype and allele frequencies of apo E polymorphism in cases of
      overweight/obesity showed no significant statistical difference compared to those
      of controls. In the control group, both apo E4 and E3 allele carriers had the
      higher serum LDL-C and lower triglycerides (TGs) and apo E concentrations than
      those with apo E2 carriers, while apo E2 allele carriers had higher serum apo C
      II levels than apo E3 carriers (P < 0.05). In overweight/obese group, genotype
      related low density Lipoprotein-Cholesterol (LDL-C) variations were also evident,
      with the changes being in a same direction as the effect in the controls, and apo
      B100 levels were decreased and apo E increased in apo E2 allele carriers when
      compared with respective apo E4 and apo E4/apo E3 allele carriers (all P < 0.05).
      CONCLUSION: Polymorphism of the apo E gene is associated with altered plasma LDL
      C and TG, as well as apo B, apo C-II, and apo E concentrations. The effects on
      TG, apo B, and apo C-II levels are BMI dependent in Chinese population of Chengdu
      area.

PMID- 22628238
TI  - Serum creatinine determined by Jaffe, enzymatic method, and isotope dilution
      liquid chromatography-mass spectrometry in patients under hemodialysis.
AB  - OBJECTIVES: Serum creatinine is an important clinical marker for renal clearance.
      However, the Jaffe method had much interference and the accuracy had not been
      tested in patients under hemodialysis (HD) with standard isotope dilution-liquid
      chromatography-mass spectrometry (IDLCMS) method. The validity of enzymatic
      method is also unknown. METHODS: The predialysis serum creatinine levels of 126
      patients under regular HD for 3 months were checked by Jaffe, enzymatic, and
      IDLCMS methods. We compared the value of the Jaffe and enzymatic to that of
      IDLCMS in linear regression model. And we also tried to find the clinical
      parameters that influence the difference between Jaffe vs. IDLCMS and enzymatic
      vs. IDLCMS method. RESULTS: We found significant underestimate serum creatinine
      in uremic patients by Jaffe and enzymatic methods. Serum glucose and globulin are
      positive biases, whereas albumin, potassium, and phosphorus are negative biases.
      Enzymatic method is less affected by serum glucose and serum protein. Albumin
      acts differently in uremic serum compared to the results of mixing them with
      normal serum. CONCLUSIONS: For uremic patients, in whom creatinine level is high
      and many of them suffered from diabetes mellitus, serum creatinine can be either
      under- or overestimated by Jaffe method. Enzymatic method is less affected and
      may be a better method.

PMID- 22628239
TI  - The use of oral fluid samples spotted on filter paper for the detection of
      measles virus using nested rt-PCR.
AB  - Measles is the leading cause of death in infants, although a vaccine is available
      for its prevention. At this stage of measles elimination and eradication, it is
      so important to confirm clinically diagnosed measles cases in the laboratory but,
      developing countries have troubles in collecting and maintaining the cold chain
      of the specimens while transporting them to the laboratories. Therefore, filter
      papers are good candidates for simplification of specimen collection and
      transportation. In this research, the effects of the temperature, at which the
      dried specimens were kept, and the time duration the dried specimens were kept
      before being tested, were studied. Since there were not enough patients' oral
      fluid samples available, a nested reverse transcriptase PCR (RT-PCR) that
      detected measles virus (MV) from dried filter papers was set up using MV infected
      cells diluted in sterile phosphate-buffered saline (PBS). Dried specimens were
      stored at -25 degrees C, 4 degrees C, and room temperature for 1 day, 1, 2, and 3
      weeks before being tested. This method was then applied to filter paper oral
      fluids collected from nine clinically diagnosed measles patients in Iran in 2010
      which were tested after being kept at room temperature for 1 day, 1 and 3 weeks
      after preparation. The results showed that dried oral fluids on filter papers are
      reliable specimens for the detection of MV RNA using nested RT-PCR, but the
      nested RT-PCR results of low titer viruses dried onto filter papers are not
      reproducible and reliable.

PMID- 22628240
TI  - Rhodium-catalyzed cascade reactions of dienynes leading to substituted
      dihydronaphthalenes and naphthalenes.

PMID- 22628241
TI  - Curcumin inhibits proliferation and induces apoptosis of human colorectal cancer
      cells by activating the mitochondria apoptotic pathway.
AB  - Curcumin, a natural plant extract from Curcuma longa, is known for its anti
      carcinogenic and chemopreventive effects on a variety of experimental cancer
      models. In this study, we evaluated the effects of curcumin and elucidated its
      mechanism in human colorectal carcinoma cells. Cell viability assay showed that
      curcumin significantly inhibited the growth of LoVo cells. Curcumin treatment
      induced the apoptosis accompanied by ultra-structural changes and release of
      lactate dehydrogenase in a dose-dependent manner. Moreover, treatment with 0-30
      ug/mL curcumin decreased the mitochondrial membrane potential and activated the
      caspase-3 and caspase-9 in a dose- and time-dependent manner. Nuclear and annexin
      V/PI staining showed that curcumin induced the apoptosis of LoVo cells. FACS
      analysis revealed that curcumin could induce the cell cycle arrest of LoVo cells
      at the S phase. Furthermore, western blotting analysis indicated that curcumin
      induced the release of cytochrome c, a significant increase of Bax and p53 and a
      marked reduction of Bcl-2 and survivin in LoVo cells. Taken together, our results
      suggested that curcumin inhibited the growth of LoVo cells by inducing apoptosis
      through a mitochondria-mediated pathway.

PMID- 22628242
TI  - Frontonasal dysplasia, callosal agenesis, basal encephalocele, and eye anomalies
      syndrome with a partial 21q22.3 deletion.
AB  - We describe a girl with a phenotype characterized by frontonasal dysplasia,
      callosal agenesis, basal encephalocele, and eye anomalies who presents a
      46,XX,r(21) karyotype. Array-comparative genomic hybridization using the
      Afflymetrix 100K DNA oligoarray set showed an interstitial deletion 21q22.3 of
      approximately 219 kb. Conventional karyotype of both parents was normal, and it
      was not possible to perform the molecular studies. In this report we raise the
      hypothesis that the deleted genes located at 21q22.3 could account to the
      phenotype.

PMID- 22628243
TI  - Inorganic composition and filler particles morphology of conventional and self
      adhesive resin cements by SEM/EDX.
AB  - The purpose of this study was to characterize the inorganic components and
      morphology of filler particles of conventional and self-adhesive, dual-curing,
      resin luting cements. The main components were identified by energy dispersive X
      ray spectroscopy microanalysis (EDX), and filler particles were morphologically
      analyzed by scanning electron microscopy (SEM). Four resin cements were used in
      this study: two conventional resin cements (RelyX ARC/3M ESPE and Clearfil
      Esthetic Cement/Kuraray Medical) and two self-adhesive resin cements (RelyX
      Unicem/3M ESPE and Clearfil SA Luting/Kuraray Medical). The materials (n = 5)
      were manipulated according to manufacturers' instructions, immersed in organic
      solvents to eliminate the organic phase and observed under SEM/EDX. Although EDX
      measurements showed high amount of silicon for all cements, differences in
      elemental composition of materials tested were identified. RelyX ARC showed
      spherical and irregular particles, whereas other cements presented only irregular
      filler shape. In general, self-adhesive cements contained higher filler size than
      conventional resin luting cements. The differences in inorganic components and
      filler particles were observed between categories of luting material and among
      them. All resin cements contain silicon, however, other components varied among
      them.

PMID- 22628244
TI  - The potential clinical relevance of visible particles in parenteral drugs.
AB  - Visible particulates (VP) are one subclass of defects seen during the final
      visual inspection of parenteral products and are currently one of the top ten
      reasons for recalls 1,2. The risk posed by particles is still unclear with
      limited experience reported in humans but remains an important consideration
      during the manufacture and use of parenteral products. From the experimental and
      clinical knowledge of the distribution of particulate matter in the body,
      clinical complications would include events occurring around parenteral
      administration e.g., as a result of mechanical pulmonary artery obstruction and
      injection site reaction, or sub-acute or chronic events e.g., granuloma. The
      challenge is to better understand the implication for patients of single vials
      with VP and align the risk with the probabilistic detection process used by
      manufacturers for accept/reject decisions of individual units of product.

PMID- 22628245
TI  - Nanoparticulate iron oxide tubes from microporous organic nanotubes as stable
      anode materials for lithium ion batteries.

PMID- 22628246
TI  - Why does clustering matter in orthodontic trials?
AB  - Clustering in RCTs occurs when participants or units are allocated to an
      intervention in a group rather than independently or when multiple measurements
      are taken from the same individual. Cluster RCTs occur frequently in clinical
      orthodontic research; however, only a quarter of published trials take account of
      the effects of clustering in the design and analysis of these trials. The effects
      of clustering needs to be considered when calculating the sample size required to
      detect a difference in treatment effect, obtaining consent for participation in
      the trial and finally the analysis of the data.

PMID- 22628247
TI  - Bactericidal activity of the organo-tellurium compound AS101 against Enterobacter
      cloacae.
AB  - OBJECTIVES: The antibacterial effect of the organo-tellurium compound AS101 on
      the Gram-negative bacterium Enterobacter cloacae is shown in this study for the
      first time. METHODS: The antimicrobial effect of the drug was shown by inhibition
      of growth, by inhibition of biofilm formation and by its ability to penetrate the
      bacterial cell and to cause damage and ultrastructural changes. RESULTS: AS101
      was found to be a bactericidal drug with MICs and MBCs of 9.4 mg/L. It inhibits
      bacterial growth and causes a six orders of magnitude decrease in viability in a
      protein-rich medium, but not in a protein-poorer medium, unless 2-mercaptoethanol
      is added. Subinhibitory concentrations inhibit motility and biofilm formation.
      AS101 enters the bacterium through its porins and causes bacterial damage to
      Na(+)/K(+) pumps and leakage of potassium, phosphorous and sulphur.
      Ultrastructural changes within the bacterial cell and on its surface demonstrate
      an incomplete surface with a concavity in the centre that looks like a hole from
      which aggregates are liberated as well as cell lysis. CONCLUSIONS: AS101 has
      antibacterial activity, which may be useful against E. cloacae and other species
      of Enterobacteriaceae as a substitute for current antibiotics that have become
      ineffective due to increasing bacterial resistance.

PMID- 22628248
TI  - A peptide based on homologous sequences of the beta-barrel assembly machinery
      component BamD potentiates antibiotic susceptibility of Pseudomonas aeruginosa.
AB  - OBJECTIVES: The beta-barrel assembly machinery (BAM) complex plays a critical
      role in outer membrane protein (OMP) biogenesis. The outer membrane (OM) of
      Pseudomonas aeruginosa is centrally involved in mechanisms of antibiotic
      resistance. This study aimed to identify effects of a synthetic peptide based on
      conserved sequences in the putative BamA-binding region of BamD, focusing on
      antibiotic susceptibility and OMP characteristics in P. aeruginosa. METHODS: We
      synthesized a peptide FIRL (Phe-Ile-Arg-Leu-CONH(2)) with a sequence related to
      that of the BamD protein. We assessed antibiotic susceptibility of P. aeruginosa
      PAO1 using the chequerboard method and a time-kill assay. Changes in OMPs and in
      OM permeability were examined using SDS-PAGE, western blot analysis and
      nitrocefin assays. The combined effects of the peptide and antibiotics were
      investigated using a mouse pneumonia model. RESULTS: Although the peptide alone
      exerted no antimicrobial effect, it reduced the MICs of colistin, levofloxacin,
      erythromycin, vancomycin and rifampicin for P. aeruginosa PAO1 by 4-fold or more.
      Time-kill tests revealed bacterial numbers were significantly reduced after 2 h
      of incubation with the peptide plus colistin or levofloxacin. Moreover, in the
      presence of the peptide, expression of OprM was reduced by a third, and OM
      permeability was increased. The combination of the peptide (2.08 mg/kg) and
      colistin (1.25 mg/kg) significantly reduced P. aeruginosa by more than 1 log
      cfu/mL in a mouse pneumonia model. CONCLUSIONS: We show, for the first time, that
      a synthetic peptide based on homologous sequences of BamD can potentiate
      antibiotic susceptibility of P. aeruginosa.

PMID- 22628249
TI  - Saethre-Chotzen phenotype with learning disability and hyper IgE phenotype in a
      patient due to complex chromosomal rearrangement involving chromosomes 3 and 7.
AB  - The authors describe on a Brazilian girl with coronal synostosis, facial
      asymmetry, ptosis, brachydactyly, significant learning difficulties, recurrent
      scalp infections with marked hair loss, and elevated serum immunoglobulin E.
      Standard lymphocyte karyotype showed a small additional segment in
      7p21[46,XX,add(7)(p21)]. Deletion of the TWIST1 gene, detected by Multiplex
      Ligation Probe-dependent Amplification (MPLA) and array-CGH, was consistent with
      phenotype of Saethre-Chotzen syndrome. Array CGH also showed deletion of four
      other genes at 7p21.1 (SNX13, PRPS1L1, HD9C9, and FERD3L) and the deletion of six
      genes (CACNA2D2, C3orf18, HEMK1, CISH, MAPKAPK3, and DOCK3) at 3p21.31. Our case
      reinforces FERD3L as candidate gene for intellectual disability and suggested
      that genes located in 3p21.3 can be related to hyper IgE phenotype.

PMID- 22628250
TI  - Molecular imaging of adrenal neoplasms.
AB  - The adrenal glands are complex structures from which a variety of benign and
      malignant tumors may arise and are a common site of metastatic disease. Several
      radiopharmaceuticals are used for imaging the adrenals, including I-123/I-131
      metaiodobenzylguanidine (MIBG), norcholesterol derivatives, In-111 pentetreotide
      and Ga-68 somatostatin analogs, [F-18]fluorodeoxyglucose, [F-18]fluorodopa, [F
      18]fluorodopamine, C-11 meta hydroxyephedrine, and C-11/F-18/I-123 Metomidate
      (MTO) or its analogs. In this review we focus on the role of these reagents in
      metastatic lesions, cortical neoplasms, pheochromocytoma/paraganglioma, and
      neuroblastoma (NB).

PMID- 22628251
TI  - Effect of lysine addition on growth of black iguana (Ctenosaura pectinata).
AB  - The effects of the addition of lysine to commercial feed given to captive black
      iguana (Ctenosaura pectinata) were evaluated in terms of growth and feed
      digestibility. Twenty-eight-day-old black iguana with an initial weight of 5.5 +/
      0.3 g were housed individually in cages measuring 45 * 45 * 45 cm. The
      experiment lasted 150 days. The ambient temperature ranged from 28 to 35 degrees
      C with a relative humidity of 60 to 95%. Treatments consisted of the addition of
      different percentages of lysine to the feed (0.0, 0.1, 0.2, and 0.3%, dry matter
      [DM] base). There was a linear response (P < 0.01) in daily gain (68, 112, 118,
      and 151 mg/d) and daily intake (251, 289, 297, and 337 mg/d) for levels from 0 to
      0.3%, respectively, as well in the growth in head size, snout-vent length, and
      total length. The digestibility of DM, neutral detergent fiber, and acid
      detergent fiber were reduced linearly (P < 0.01) as lysine levels increased.
      Intake and digestibility were negatively correlated (r = -0.74; P < 0.001). It is
      concluded that the addition of lysine to the black iguana diet in the first
      months of life is important to stimulate growth and intake.

PMID- 22628252
TI  - Uranyl hybrid material derived from in situ ligand synthesis: formation,
      structure, and an unusual phase transformation.

PMID- 22628254
TI  - Enantioselective sensing of chiral amino alcohols with a stereodynamic
      arylacetylene-based probe.
AB  - Enantioselective induced circular dichroism analysis of amino alcohols has been
      accomplished using a conformationally flexible arylacetylene-based probe
      exhibiting two terminal aldehyde groups. The chirality of the amino alcohol
      substrates is imprinted on the stereodynamic receptor upon [1 + 2] condensation,
      which ultimately generates a strong chiroptical response. The distinct induced
      circular dichroism effects of the diimines obtained can be used for
      enantioselective sensing and enantiomeric excess determination of a wide range of
      substrates.

PMID- 22628253
TI  - Three new patients with FATCO: fibular agenesis with ectrodactyly.
AB  - We document three new patients with fibular agenesis, tibial campomelia, and
      oligosyndactyly (FATCO). Two of these individuals had tetramelic manifestations
      while the third had bilateral abnormalities of the lower limbs. These patients
      and others reported as FATCO seem to belong to the phenotype "fibular aplasia
      with ectrodactyly." Genetic screening for CNVs and mutations in the TP63 and
      WNT10B genes did not show any genetic abnormalities. (c)

PMID- 22628255
TI  - Cytochemical investigation of the digestive gland of two strombidae species
      (Strombus gigas and Strombus pugilis) in relation to the nutrition.
AB  - Strombus gigas and Strombus pugilis are threatened species and aquaculture
      represents a good alternative solution to the fishing. In this study, we
      highlighted the intracellular digestion process in the digestive gland of two
      Strombidae species, S. gigas and Strombuspugilis, by the cytochemical
      characterization of two lysosomal enzymes: acid phosphatase and arylsulfatase. In
      order to check the efficiency of artificial food digestion, we conducted the
      characterization on freshly collected, starved and artificially fed individuals
      of S. pugilis. TEM observations of digestive gland sections from freshly
      collected individuals of both species revealed the presence of acid phosphatase
      and arylsulfatase activity mostly located in the apical third of digestive cells.
      Both enzymes were also detected in artificially fed individuals. In response to
      the starvation, acid phosphatase is not produced anymore by digestive cells,
      while arylsulfatase is still present. To our knowledge, this is the first
      cytochemical validation of intracellular digestion of artificial food in
      Strombidae. This study highlights the intracellular digestion of artificial food
      developed for Strombidae aquaculture. Moreover, we have shown that the lysosomal
      activity could be used as a feed index.

PMID- 22628258
TI  - Laryngeal stenosis in a patient with severe congenital neutropenia.
AB  - OBJECTIVES/HYPOTHESIS: We report the first case of laryngeal stenosis with
      granuloma in a patient with severe congenital neutropenia (SCN). STUDY DESIGN:
      Case report and retrospective review. METHODS: Review of medical records.
      RESULTS: A 6-year-old female who was diagnosed with SCN presented with a cough
      and wheezing. An endoscopic study revealed laryngeal stenosis with granuloma.
      Tracheotomy and direct laryngoscopy were performed under general anesthesia, and
      administration of granulocyte colony-stimulating factor was started. The
      laryngeal granuloma disappeared 3 weeks later, and the tracheal stoma was closed.
      CONCLUSIONS: Presence of a laryngeal lesion should be considered in SCN patients
      with persistent airway symptoms.

PMID- 22628259
TI  - Hormonal and behavioral variation in pied tamarins housed in different management
      conditions.
AB  - Pied tamarins are an endangered Amazonian primate that has limited breeding
      success in zoos. Unfortunately, little is known about their reproductive biology
      and adrenocortical activity. Objectives were: (1) determine if fecal hormones
      could be utilized to monitor gonadal and adrenocortical activity; (2)
      characterize male and female gonadal and adrenocortical hormones; and (3)
      determine if there were differences between adrenocortical activity and behavior
      in a nonbreeding, on-exhibit (NB-ON) pair compared to a breeding, off-exhibit (B
      OFF) pair. Fecal samples were collected from four (two males; two females)
      individuals. Hormones were analyzed for fecal progesterone (FPM), androgen (FAM),
      and glucocorticoid (FGM) metabolites by enzyme immunoassay. Behavioral
      observations were conducted for 6 months. Data were collected on instantaneous
      behavior, location, and all occurrences of intraspecific behaviors. Fecal
      progesterone metabolites were validated by pregnancy (mean +/- SE, pregnant:
      28.47 +/- 1.60 MUg/g; nonpregnant: 8.63 +/- 0.89 MUg/g). Fecal androgen
      metabolites were higher (T = 31,971, P < 0.05) in the B-OFF male (863.66 +/-
      46.30 MUg/g) than the NB-ON male (838.63 +/- 60.70 MUg/g). Fecal glucocorticoid
      metabolites were validated by response to veterinary procedure with elevated
      values (7.31 +/- 1.48 MUg/g) seven times the baseline (0.37 +/- 0.04 MUg/g) at 24
      hr postphysical. Females had higher baseline FGM than the males (P < 0.05).
      Baseline FGM were higher (P < 0.05) in the NB-ON female (0.93 +/- 0.03 MUg/g)
      compared to the B-OFF female (0.38 +/- 0.02 MUg/g). Similarly, the NB-ON male's
      FGM baseline (0.71 +/- 0.03 MUg/g) were higher (P < 0.05) than the B-OFF male
      (0.21 +/- 0.01 MUg/g). Behavioral data revealed stereotypical behaviors in the NB
      ON pair but no stereotypical behaviors in the B-OFF pair. Fecal hormone
      monitoring and behavioral analysis may provide insight on the limited breeding
      success of pied tamarins in zoos.

PMID- 22628261
TI  - Hearing loss in skeletal dysplasia patients.
AB  - A hearing screening program was performed to determine the prevalence of hearing
      loss and abnormal tympanometry in individuals with short-stature skeletal
      dysplasias attending a national meeting. Behavioral audiometry, otoacoustic
      emission testing, and tympanometry were used to assess hearing. Failed hearing
      screen was defined as hearing >= 35 dB at one or more frequencies or by "fail" on
      otoacoustic emissions. One hundred ten of 112 subjects completed the screening.
      58 (51.8%) were children. Seventy-three (65.2%) had achondroplasia, 34 (30.4%)
      had one of 11 other diagnoses, and 5(4.4%) were undiagnosed. 25.8% of children
      failed hearing screening in one or both ears, while 46.3% of adults failed in one
      or both ears. 55.1% of adults and 25.0% of children with achondroplasia failed
      screening. Abnormal hearing was also found in the some patients with
      spondyloepiphyseal dysplasia congenital (SEDC; 75%), diastrophic dysplasia (66%),
      and Morquio (66%). Hearing was normal in those with hypochondroplasia,
      pseudoachondroplasia, and microcephalic osteodysplastic primordial dwarfism.
      Tympanometry was abnormal in at least one ear in 53.3% of children and 38.5% of
      adults. Abnormal tympanometry in the absence of functioning tympanostomy tubes
      was associated with 9.5 greater odds of hearing loss in children and 2.8 greater
      odds of hearing loss in the total cohort. Only 3 (2.7%) respondents reported the
      use of hearing aids. Hearing loss and middle ear disease are common in both
      children and adults with skeletal dysplasia. Adults were more likely to fail
      hearing screening than children. Abnormal tympanometry is associated with hearing
      loss. Hearing screening with appropriate intervention is recommended for these
      patients.

PMID- 22628260
TI  - Cytotoxic activity and antioxidant capacity of purified lichen metabolites: an in
      vitro study.
AB  - The purpose of this study was to investigate the effects of six lichen
      metabolites (diffractaic acid, lobaric acid, usnic acid, vicanicin, variolaric
      acid, protolichesterinic acid) on proliferation, viability and reactive oxygen
      species (ROS) level towards three human cancer cell lines, MCF-7 (breast
      adenocarcinoma), HeLa (cervix adenocarcinoma) and HCT-116 (colon carcinoma).
      Cells were treated with different concentrations (2.5-100 MUM) of these compounds
      for 48 h. In this comparative study, our lichen metabolites showed various
      cytotoxic effects in a concentration-dependent manner, and usnic acid was the
      most potent cytotoxic agent, while variolaric acid did not inhibit the
      proliferation of any of the three cell lines used. All tested lichen compounds
      did not exhibit free radical scavenging activity using the 1,1-diphenyl-2
      picrylhydrazyl (DPPH) assay. The lichen metabolites did not significantly
      increase the intracellular ROS level and did not prevent oxidative injury induced
      by t-butylhydroperoxide in HeLa cells. To better clarify the mechanism(s) of
      cytotoxic effect induced by protolichesterinic acid in HeLa cells, we
      investigated apoptotic markers such as condensation and fragmentation of nuclear
      chromatin and activation of caspase-3, 8 and 9. Our results revealed that the
      antiproliferative activity of 40 MUM protolichesterinic acid in HeLa cells is
      related to its ability to induce programmed cell death involving caspase-3, 8 and
      9 activation.

PMID- 22628263
TI  - Tailoring of mesenchymal stem cells behavior on plasma-modified
      polytetrafluoroethylene.
AB  - By altering the surface properties of polytetrafluoroethylene (PTFE) substrates
      using a special PIII technique, mesenchymal stem cells (MSCs) proliferation and
      osteogenesis can be promoted in culture without osteogenic supplements. The
      structures are created intrinsically in the PTFE for no risk of materials
      delamination. Large-scale features and locally different functions can also be
      readily produced on the same substrate by this technique.

PMID- 22628264
TI  - Signaling profiling at the single-cell level identifies a distinct signaling
      signature in murine hematopoietic stem cells.
AB  - Hematopoietic stem cell (HSC) function is tightly regulated by cytokine
      signaling. Although phospho-flow cytometry allows us to study signaling in
      defined populations of cells, there has been tremendous hurdle to carry out this
      study in rare HSCs due to unrecoverable critical HSC markers, low HSC number, and
      poor cell recovery rate. Here, we overcame these difficulties and developed a
      "HSC phospho-flow" method to analyze cytokine signaling in murine HSCs at the
      single-cell level and compare HSC signaling profile to that of multipotent
      progenitors (MPPs), a cell type immediately downstream of HSCs, and commonly used
      Lin(-) cKit(+) cells (LK cells, enriched for myeloid progenitors). We chose to
      study signaling evoked from three representative cytokines, stem cell factor
      (SCF) and thrombopoietin (TPO) that are essential for HSC function and
      granulocyte macrophage-colony-stimulating factor (GM-CSF) that is dispensable for
      HSCs. HSCs display a distinct TPO and GM-CSF signaling signature from MPPs and LK
      cells, which highly correlates with receptor surface expression. In contrast,
      although majority of LK cells express lower levels of cKit than HSCs and MPPs,
      SCF-evoked ERK1/2 activation in LK cells shows a significantly increased
      magnitude for a prolonged period. These results suggest that specific cellular
      context plays a more important role than receptor surface expression in SCF
      signaling. Our study of HSC signaling at the homeostasis stage paves the way to
      investigate signaling changes in HSCs under conditions of stress, aging, and
      hematopoietic diseases.

PMID- 22628265
TI  - Ethanol extract of Magnolia officinalis prevents lipopolysaccharide-induced
      memory deficiency via its antineuroinflammatory and antiamyloidogenic effects.
AB  - Magnolia bark contains several compounds such as magnolol, honokiol, 4-O
      methylhonokiol, obovatol, and other neolignan compounds. These compounds have
      been reported to have various beneficial effects in various diseases. There is
      sufficient possibility that ethanol extract of Magnolia officinalis is more
      effective in amyloidogenesis via synergism of these ingredients.
      Neuroinflammation has been known to play a critical role in the pathogenesis of
      Alzheimer's disease (AD). We investigated whether the ethanol extract of M.
      officinalis (10 mg/ kg in 0.05% ethanol) prevents memory dysfunction and
      amyloidogenesis in AD mouse model by intraperitoneal lipopolysaccharide (LPS, 250
      ug/ kg/day for seven times) injection. We found that ethanol extract of M.
      officinalis prevented LPS-induced memory deficiency as well as inhibited the LPS
      induced elevation of inflammatory proteins, such as inducible nitric oxide
      synthase and cyclooxygenase 2, and activation of astrocytes and microglia. In
      particular, administration of M. officinalis ethanol extract inhibited LPS
      induced amyloidogenesis, which resulted in the inhibition of amyloid precursor
      protein, beta-site amyloid-precursor-protein-cleaving enzyme 1 and C99. Thus,
      this study shows that ethanol extract of M. officinalis prevents LPS-induced
      memory impairment as well as amyloidogenesis via inhibition of neuroinflammation
      and suggests that ethanol extract of M. officinalis might be a useful
      intervention for neuroinflammation-associated diseases such as AD.

PMID- 22628266
TI  - Design, synthesis, and biological evaluation of 2-aminobenzanilide derivatives as
      potent and selective HDAC inhibitors.
AB  - Epigenetic regulation is an essential process for the normal functioning of
      genes. Therefore, targeting epigenetic dysregulation in cancer may be a valid
      therapeutic approach for the treatment of this severe disease. Histone
      deacetylases (HDACs) are enzymes involved in the regulation of epigenetic post
      translational modifications; because they are overexpressed in many types of
      cancer, HDACs are valuable targets for the development of new anticancer agents.
      A large series of 2-aminobenzanilides linked at the 4'-position to alpha-amino
      acid amides, arenes, and heteroarenes through a methylene bridge were designed,
      synthesized, and tested as novel HDAC inhibitors. Several compounds showed IC(50)
      values in the two-digit nanomolar range in hrHDAC1 inhibition assays, lower than
      that of the reference compound MS-275. They also showed interesting selectivity
      profiles, as confirmed by western blot assays.

PMID- 22628267
TI  - Bilateral choanal atresia in a cat.
AB  - A 7-month-old female spayed domestic shorthair cat was presented for
      investigation of stertor, open mouth breathing without apparent distress, and
      chronic bilateral nasal discharge that was unresponsive to antibiotics. Complete
      bilateral bony choanal atresia was diagnosed with computed tomography and
      nasopharyngoscopy. Choanal atresia is an uncommon congenital condition where the
      choana (nasal passage into the nasopharynx) is blocked by abnormal bone or soft
      tissue uni- or bilaterally. The cat's clinical signs improved dramatically
      immediately after trans-palatal surgical correction. Post-surgical complications
      included the development of nasopharyngeal scar tissue and subsequent stenosis,
      persistent right-sided nasal discharge, and permanent damage to the right eye
      (blindness and cataract formation). Nasopharyngeal stenosis was managed with
      repeated balloon dilatations and temporary stenting, and the owner reported an
      excellent quality of life at 8-month follow-up. Bilateral bony choanal atresia
      has not been previously reported in cats. Uni- or bilateral choanal atresia
      should be considered in young cats presenting with refractory stertor, chronic
      nasal discharge, and/or open mouth breathing.

PMID- 22628268
TI  - A case of feline injection-site sarcoma at the site of cisplatin injections.
AB  - A spayed 14-year-old female domestic shorthair cat presented with a squamous cell
      carcinoma of the nasal planum and was treated with intralesional chemotherapy.
      During nasal infiltrations with cisplatin mixed with the cat's own serum, a new
      carcinomatous lesion developed at the medial canthus of the right eye, which was
      also treated using intralesional chemotherapy. Two months after the treatment
      course, the cat developed a new mass at the site of the eyelid chemotherapy,
      which was diagnosed as a soft tissue sarcoma. At the owner's request, the tumour
      was marginally excised, but it recurred after 10 months. No lung or lymph node
      metastases were evident at the time of euthanasia. The histotype of the tumour,
      the coincidence with injections and the histological description make the
      hypothesis of an injection-site sarcoma likely. To the authors' knowledge, this
      is the first case of an injection-site sarcoma at the site of a cisplatin
      injection.

PMID- 22628269
TI  - Clinical evaluation of urine Histoplasma capsulatum antigen measurement in cats
      with suspected disseminated histoplasmosis.
AB  - Diagnosis of Histoplasma capsulatum infection in cats traditionally relies upon
      identification of organisms in circulating monocytes or in tissue specimens from
      affected organs. In this retrospective study, results of a urine antigen assay
      were compared with standard diagnostic methods in cats with clinical signs
      suggestive of histoplasmosis. Antigenuria was detected in 17/18 cats with a
      histopathologic or cytopathologic diagnosis of histoplasmosis. This preliminary
      evaluation of the Histoplasma urine antigen test suggests it may be a useful aid
      in diagnosing this disease in cats.

PMID- 22628270
TI  - Severe hypoglycaemia in a cat with primary hypoadrenocorticism.
AB  - This case report describes a 3-year-old, castrated male, mixed-breed cat with
      historical, clinical and laboratory findings compatible with primary
      hypoadrenocorticism, confirmed by adrenocorticotropic hormone stimulation test.
      Severe but asymptomatic hypoglycaemia was an unexpected biochemical finding and
      resolved after fludrocortisone acetate and prednisolone treatment. This case
      demonstrates that hypoadrenocorticism should be included in the differentials
      list of severe hypoglycaemia in cats.

PMID- 22628271
TI  - Loring Withee Pratt, MD, FACS 1918-2012.

PMID- 22628272
TI  - Attitudes toward prenatal genetic testing for Treacher Collins syndrome among
      affected individuals and families.
AB  - Treacher Collins syndrome (TCS) is a craniofacial syndrome that is both
      phenotypically variable and heterogeneous, caused by mutations in the TCOF1,
      POLR1C, and POLR1D genes. We examined attitudes towards TCS prenatal genetic
      testing among affected families using a telephone questionnaire. Participants
      were 31 affected adults and relatives recruited primarily through families cared
      for in the mid-Atlantic region. Nineteen participants (65%) reported that they
      would take a TCS prenatal genetic test which could not predict degree of disease
      severity. Interest in TCS genetic testing was associated with higher income,
      higher concern about having a child with TCS, lower religiosity, lower concern
      about genetic testing procedures, and having a sporadic rather than familial
      mutation. Over half reported that their decision to have TCS genetic testing
      would be influenced a great deal by their desire to relieve anxiety and attitudes
      toward abortion. Ten participants (32%) reported that they would be likely to end
      the pregnancy upon receiving a positive test result; this was lower amongst TCS
      affected individuals and higher amongst participants with children with TCS.
      Genetics healthcare providers need to be aware of affected individuals' and
      families' attitudes and interest in prenatal genetic testing for TCS, and the
      possible implications for other craniofacial disorders, so that patients'
      information needs can be met.

PMID- 22628274
TI  - Graphene oxide as an optical biosensing platform.
AB  - Since graphene exhibits innovative mechanical, electrical, thermal, and optical
      properties, this 2D material is increasingly attracting attention and is under
      active research. Among the various graphene forms with lattice-like
      nanostructure, graphene oxide (GO) displays advantageous characteristics as a
      biosensing platform due to its excellent capabilities for direct wiring with
      biomolecules, a heterogeneous chemical and electronic structure, the possibility
      to be processed in solution and the ability to be tuned as insulator,
      semiconductor or semi-metal. Moreover, GO photoluminescences with energy transfer
      donor/acceptor molecules exposed in a planar surface and is even proposed as a
      universal highly efficient long-range quencher, which is opening the way to
      several unprecedented biosensing strategies. Here, the rationale behind the use
      of GO in optical biosensing applications is discussed by describing different
      potentially exploitable properties of GO, and an overview of the current
      approaches are presented along with future perspectives and challenges.

PMID- 22628275
TI  - Characterization of renal progenitors committed toward tubular lineage and their
      regenerative potential in renal tubular injury.
AB  - Recent studies implicated the existence in adult human kidney of a population of
      renal progenitors with the potential to regenerate glomerular as well as tubular
      epithelial cells and characterized by coexpression of surface markers CD133 and
      CD24. Here, we demonstrate that CD133+CD24+ renal progenitors can be
      distinguished in distinct subpopulations from normal human kidneys based on the
      surface expression of vascular cell adhesion molecule 1, also known as CD106.
      CD133+CD24+CD106+ cells were localized at the urinary pole of Bowman's capsule,
      while a distinct population of scattered CD133+CD24+CD106- cells was localized in
      the proximal tubule as well as in the distal convoluted tubule. CD133+CD24+CD106+
      cells exhibited a high proliferative rate and could differentiate toward the
      podocyte as well as the tubular lineage. By contrast, CD133+CD24+CD106- cells
      showed a lower proliferative capacity and displayed a committed phenotype toward
      the tubular lineage. Both CD133+CD24+CD106+ and CD133+CD24+CD106- cells showed
      higher resistance to injurious agents in comparison to all other differentiated
      cells of the kidney. Once injected in SCID mice affected by acute tubular injury,
      both of these populations displayed the capacity to engraft within the kidney,
      generate novel tubular cells, and improve renal function. These properties were
      not shared by other tubular cells of the adult kidney. Finally, CD133+CD24+CD106-
      cells proliferated upon tubular injury, becoming the predominating part of the
      regenerating epithelium in patients with acute or chronic tubular damage. These
      data suggest that CD133+CD24+CD106- cells represent tubular-committed progenitors
      that display resistance to apoptotic stimuli and exert regenerative potential for
      injured tubular tissue.

PMID- 22628278
TI  - Spectroscopic characterization of lycopene extract from Lycopersicum esculentum
      (Tomato) and its evaluation as a chemopreventive agent against experimental
      hepatocarcinogenesis in mice.
AB  - The present study was designed to characterize the lycopene extract (LycT)
      prepared from tomatoes (Lycopersicum esculentum) and then to evaluate its
      chemopreventive efficacy in N-diethylnitrosamine (NDEA)-induced experimental
      hepatocarcinogenesis in female Balb/c mice. The extraction of lycopene was
      carried out using hexane/acetone/ethanol as an extracting medium and then
      characterized by ultraviolet-visible, nuclear magnetic resonance and Fourier
      transform infrared spectroscopy. Chemopreventive efficacy of characterized LycT
      in vivo was evaluated in terms of hepatic tumour incidence, multiplicity, burden,
      hepatosomatic index and animal survival rate. Results indicated that average
      lycopene content of the tomato was 11.6-14 mg/kg tomato weight. Spectroscopic
      data confirmed the structural characteristics of lycopene in the extract. In the
      animal study, reduction in tumour incidence (42.05%), tumour burden (1.39) and
      tumour multiplicity (3.42) was observed upon LycT pretreatment to NDEA-treated
      animals. Histopathological analysis unravelled that the increased survival rate
      in LycT + NDEA-treated animals was due to the delay in the formation of
      aggressive tumour nodules. These observations indicate that lycopene seems to be
      an able candidate for chemoprevention in hepatocarcinogenesis resulting from NDEA
      insults.

PMID- 22628280
TI  - Phenotypic progression of skeletal anomalies in CLOVES syndrome.
AB  - Overgrowth syndromes, defined as genetic disorders in which there is
      disproportionate somatic growth, are challenging to diagnose due to their
      heterogeneous presentations and possible differing genetic etiologies. CLOVES
      syndrome is characterized by congenital lipomatous overgrowth, vascular
      malformations, epidermal nevi, and skeletal abnormalities (Scoliosis). We
      describe a developmental follow up of the skeletal changes in CLOVES syndrome and
      a detailed account of its management. We demonstrate the asymmetric growth rate
      of toes responsible for the macrodactyly observed, and present additional
      phenotypic findings, including postnatal onset of abdominal symmetry and
      hepatomegaly. While the etiology of CLOVES is still a mystery, its similarity to
      Klippel-Trenaunay syndrome suggests a shared defect in a common signaling
      pathway, and its asymmetric bone overgrowth supports a mosaic genetic defect as
      its etiology.

PMID- 22628282
TI  - Bovine TB and the 'singleton protocol': reward without risk.

PMID- 22628281
TI  - Etv2 is expressed in the yolk sac hematopoietic and endothelial progenitors and
      regulates Lmo2 gene expression.
AB  - During embryogenesis, the endothelial and the hematopoietic lineages first appear
      during gastrulation in the blood island of the yolk sac. We have previously
      reported that an Ets variant gene 2 (Etv2/ER71) mutant embryo lacks hematopoietic
      and endothelial lineages; however, the precise roles of Etv2 in yolk sac
      development remains unclear. In this study, we define the role of Etv2 in yolk
      sac blood island development using the Etv2 mutant and a novel Etv2-EYFP reporter
      transgenic line. Both the hematopoietic and the endothelial lineages are absent
      in the Etv2 mutant yolk sac. In the Etv2-EYFP transgenic mouse, the EYFP reporter
      is activated in the nascent mesoderm, expressed in the endothelial and blood
      progenitors, and in the Tie2(+), c-kit(+), and CD41(+) hematopoietic population.
      The hematopoietic activity in the E7.75 yolk sac was exclusively localized to the
      Etv2-EYFP(+) population. In the Etv2 mutant yolk sac, Tie2(+) cells are present
      but do not express hematopoietic or endothelial markers. In addition, these cells
      do not form hematopoietic colonies, indicating an essential role of Etv2 in the
      specification of the hematopoietic lineage. Forced overexpression of Etv2 during
      embryoid body differentiation induces the hematopoietic and the endothelial
      lineages, and transcriptional profiling in this context identifies Lmo2 as a
      downstream target. Using electrophoretic mobility shift assay, chromatin
      immunoprecipitation, transcriptional assays, and mutagenesis, we demonstrate that
      Etv2 binds to the Lmo2 enhancer and transactivates its expression. Collectively,
      our studies demonstrate that Etv2 is expressed during and required for yolk sac
      hematoendothelial development, and that Lmo2 is one of the downstream targets of
      Etv2.

PMID- 22628283
TI  - Narrative medicine: learning through stories.

PMID- 22628284
TI  - Adding value for farmers through herd health plans.

PMID- 22628285
TI  - Asiaticoside induces type I collagen synthesis and osteogenic differentiation in
      human periodontal ligament cells.
AB  - Asiaticoside, an active ingredient extracted from Centella asiatica, has been
      widely used to promote wound healing. In this study, the effects of asiaticoside
      on proliferation, protein synthesis, and osteogenic differentiation in human
      periodontal ligament cells (HPDLs) were investigated. HPDLs were treated with
      asiaticoside at concentrations of 25, 50, and 100 ug/mL. Cell number was
      determined by MTT assay. The mRNA expression was analyzed by reverse
      transcription-polymerase chain reaction. Western blot analysis and
      immunocytochemistry were used to confirm protein synthesis. Osteogenic
      differentiation was determined by alkaline phosphatase activity, osteoblast
      marker gene expression, and in vitro mineralization. The results showed that
      asiaticoside treatment, ranging from 25 to 100 mg/mL, had no effect on
      cytotoxicity or cell proliferation. When HPDLs were treated with asiaticoside in
      serum-free medium, dose-dependent increases in the levels of fibronectin and
      collagen type I mRNA and protein were observed at 72 h. Moreover, asiaticoside
      attenuated matrix metalloproteinase-1 but enhanced tissue inhibitor of
      metalloproteinase-1 mRNA expression. The addition of asiaticoside to osteogenic
      medium resulted in an increase in alkaline phosphatase enzymatic activity, up
      regulation of osteoblast marker gene mRNA expression, and enhancement of
      mineralization by HPDLs. These results suggest the potential application of
      asiaticoside for enhancing periodontal tissue healing.

PMID- 22628286
TI  - Effect of stress during handling, seawater acclimation, confinement, and induced
      spawning on plasma ion levels and somatolactin-expressing cells in mature female
      Liza ramada.
AB  - The present experiments were designed to determine the effect of different stress
      factors; handling, seawater acclimation, confinement, and induced spawning on
      plasma cortisol, hydro mineral balance as well as changes in size, number and
      integrated intensity of somatolactin (SL)-expressing cells in Liza ramada mature
      females confined to fresh water ponds. The plasma levels of cortisol, PO(4)(3-),
      Na(+), and K(+) were higher, while Ca(2+) and Mg(2+) were lower than controls
      during transportation without anesthesia. By using clove oil (5 mg L(-1)) as an
      anesthetic during transportation, the plasma cortisol, PO(4) (3-), Na(+), and
      K(+) were similar to controls, while Ca(2+) and Mg(2+) were higher. During
      seawater acclimation, the plasma cortisol and minerals were significantly higher
      except Na(+) which was lower than controls. In addition, during induction of
      spawning, the plasma levels of cortisol, PO(4)(3-), Na(+), K(+), and Mg(2+) were
      significantly higher than controls. The SL-producing cells are located in the
      pars intermedia (PI) bordering the neurohypophysis. The stress affected the
      number, size, and immunostaining of SL-expressing cells. During seawater
      acclimation, the size and the integrated intensity of SL immunoreactivity were
      lower, but the number of these cells was higher than controls. Furthermore, the
      number, size, and the integrated intensity of SL immunoreactivity were
      significantly lower than controls during handling and after spawning, which was
      opposite to confinement. The response of SL-expressing cells in PI in parallel
      with changes in cortisol and hydro mineral balance induced by stress support the
      possible role of SL in the adaptive response of fish to stress.

PMID- 22628287
TI  - Complete trisomy 10p resulting from an extra stable telocentric chromosome.

PMID- 22628288
TI  - STD NMR study of the interactions between antibody 2G12 and synthetic
      oligomannosides that mimic selected branches of gp120 glycans.
AB  - The human immunodeficiency virus type-1 (HIV-1) is able to shield immunogenic
      peptide epitopes on its envelope spike (a trimer of two glycoproteins, gp120 and
      gp41) by presenting numerous host-derived N-linked glycans. Nevertheless, broadly
      neutralizing antibodies against gp120 and gp41 have been isolated from HIV-1
      infected patients and provide protection against viral challenge in animal
      models. Among these, the monoclonal antibody 2G12 binds to clusters of high
      mannose-type glycans that are present on the surface of gp120. These types of
      glycans have thus been envisaged as target structures for the development of
      synthetic agents capable of eliciting 2G12-like antibodies. High-resolution
      structural studies of 2G12 and chemically defined glycan-type ligands, including
      crystallographic data, have been performed to gain an insight into this
      interaction. Further studies are still required to design a carbohydrate-based
      vaccine for HIV. Our previous NMR studies highlighted different recognition modes
      of two branched synthetic oligosaccharides, a penta- and a heptamannoside, by
      2G12 in solution. In order to clarify the underlying structural reasons for such
      different behaviors, we have herein "dissected" the branches into the linear tri-
      and tetra- oligomannosides by chemical synthesis and studied their interactions
      with 2G12 in solution by saturation transfer difference (STD) NMR spectroscopy.
      The results confirm the distinct preferences of 2G12 for the studied branches and
      afford explanations for the observed differences. This study provides important
      structural information for further ligand optimizations. Possible effects of
      structural modifications on the solvent-exposed end of the ligands are also
      discussed.

PMID- 22628289
TI  - High basal gammaH2AX levels sustain self-renewal of mouse embryonic and induced
      pluripotent stem cells.
AB  - Phosphorylation of histone H2AX (gammaH2AX) is known to be the earliest indicator
      of DNA double-strand breaks. Recently, it has been shown that mouse embryonic
      stem cells (mESCs) have very high basal levels of gammaH2AX, even when they have
      not been exposed to genotoxic agents. As the specialized role of high basal
      gammaH2AX levels in pluripotent stem cells is still debated, we investigated
      whether H2AX phosphorylation is important in maintaining self-renewal of these
      cells. Here, we report that not only mESCs but also mouse-induced pluripotent
      stem cells (miPSCs), have high basal levels of gammaH2AX. We show that basal
      gammaH2AX levels decrease upon ESC and iPSC differentiation and increase when the
      cells are treated with self-renewal-enhancing small molecules. We observe that
      self-renewal activity is highly compromised in H2AX-/- cells and that it can be
      restored in these cells through reconstitution with a wild-type, but not a
      phospho-mutated, H2AX construct. Taken together, our findings suggest a novel
      function of H2AX that expands the knowledge of this histone variant beyond its
      role in DNA damage and into a new specialized biological function in mouse
      pluripotent stem cells.

PMID- 22628290
TI  - Barriers, facilitators, and recommendations related to implementing the Baby
      Friendly Initiative (BFI): an integrative review.
AB  - Despite growing evidence for the positive impact of the Baby-Friendly Initiative
      (BFI) on breastfeeding outcomes, few studies have investigated the barriers and
      facilitators to the implementation of Baby-Friendly practices that can be used to
      improve uptake of the BFI at the local or country levels. This integrative review
      aimed to identify and synthesize information on the barriers, facilitators, and
      recommendations related to the BFI from the international, peer-reviewed
      literature. Thirteen databases were searched using the keywords Baby Friendly,
      Baby-Friendly Hospital Initiative, BFI, BFHI, Ten Steps, implementation,
      adoption, barriers, facilitators, and their combinations. A total of 45 English
      language articles from 16 different countries met the inclusion criteria for the
      review. Data analysis was guided by Cooper's five stages of integrative research
      review. Using a multiple intervention program framework, findings were
      categorized into sociopolitical, organizational-level, and individual-level
      barriers and facilitators to implementing the BFI, as well as intra-, inter-, and
      extraorganizational recommendations for strengthening BFI implementation. A wide
      variety of obstacles and potential solutions to BFI implementation were
      identified. Findings suggest some priority issues to address when pursuing Baby
      Friendly designation, including the endorsements of both local administrators and
      governmental policy makers, effective leadership of the practice change process,
      health care worker training, the marketing influence of formula companies, and
      integrating hospital and community health services. Framing the BFI as a complex,
      multilevel, evidence-based change process and using context-focused research
      implementation models to guide BFI implementation efforts may help identify
      effective strategies for promoting wider adoption of the BFI in health services.

PMID- 22628291
TI  - Maternal request for in-hospital supplementation of healthy breastfed infants
      among low-income women.
AB  - BACKGROUND: While hospital policies and medical issues are important factors in
      determining exclusive breastfeeding rates, medically unnecessary supplementation
      of infants is likely to be due, in part, to maternal request for formula.
      OBJECTIVES: The goal of this project was to gain an understanding of the
      facilitating factors and decision-making processes surrounding maternal request
      for formula in the early postpartum period. METHODS: A series of 12 focus groups
      were conducted among 97 English- and Spanish-speaking low-income participants in
      California's Supplementary Nutrition Program for Women, Infants, and Children
      (WIC). Mothers were asked to share their in-hospital infant-feeding experiences.
      RESULTS: The overarching theme that emerged was "lack of preparation" for what
      the early postpartum period would be like. Specifically, the decisions to formula
      feed fell into the following categories: inadequate preparation for newborn care
      (the need for rest and unrealistic expectations about infant behavior), lack of
      preparation for the process of breastfeeding, and formula as a solution to
      breastfeeding problems. Cultural factors were not mentioned as reasons for
      supplementation. CONCLUSION: Interventions to promote in-hospital exclusive
      breastfeeding must address mothers' real and perceived barriers, specifically
      mothers' expectations related to breastfeeding and infant behavior.

PMID- 22628292
TI  - The effects of an antiosteoporosis herbal formula containing epimedii herba,
      ligustri lucidi fructus and psoraleae fructus on density and structure of rat
      long bones under tail-suspension, and its mechanisms of action.
AB  - An innovative anti-osteoporosis herbal formula containing epimedii herba,
      ligustri lucidi fructus and psoraleae fructus (ELP) has been previously shown its
      bone protecting effects in ovariectomized osteoporotic rats and also in post
      menopausal osteopenic women. This study aimed to investigate the efficacy of ELP
      against bone loss during physical inactivity or weightlessness. A hindlimb
      unloading tail-suspended rat model was used for studying the effects of ELP on
      bone mineral density (BMD) and bone micro-architecture. For in vitro mechanistic
      studies, rat mesenchymal stem cells (MSCs) and mouse macrophage cells (RAW264.7)
      were used for studying the effects of ELP on osteogenic/adipogenic
      differentiations and osteoclastogenesis, respectively. Our data illustrated that
      ELP had a significant preventive effect against bone loss induced by tail
      suspension (TS) at day 28 (p < 0.01) as indicated in the reduction in BMD loss
      and the preservation of bone micro-architecture. ELP could significantly promote
      the osteogenesis and suppress the adipogenesis (p < 0.05) in MSCs. Besides,
      significant inhibition of osteoclast formation (p < 0.01) was found in ELP
      treated RAW264.7 cells upon receptor activator of nuclear factor kappa-B ligand
      induction. Our study presents the first scientific evidence that ELP had a
      significant preventive effect against bone loss induced by TS through the actions
      of enhancing osteogenesis, suppressing adipogenesis and osteoclastogenesis.

PMID- 22628294
TI  - Transporters in cholelithiasis.
AB  - Gallstones are a common and costly disease with a projected increase in
      prevalence due to the increasing ageing population. Numerous endogenous and
      environmental factors are aetiologically related to this multifactorial disease,
      and genetic studies continue to unravel the pathobiological mechanisms related to
      gallstone formation. In particular, variants of genes encoding hepatobiliary
      transporters have been implicated in gallstone disease and, given their ability
      to influence biliary lipid composition, have undergone considerable
      investigation. Here we summarize the role of enterohepatic transporters in
      cholelithogenesis with a particular focus on pertinent ATP-binding cassette
      transporters (ABCB4, ABCB11, ABCC7, and ABCG5/G8).

PMID- 22628295
TI  - Oxidative stress in Fanconi anaemia: from cells and molecules towards prospects
      in clinical management.
AB  - Fanconi anaemia (FA) is a genetic disease featuring bone marrow failure,
      proneness to malignancies, and chromosomal instability. A line of studies has
      related FA to oxidative stress (OS). This review attempts to evaluate the
      evidence for FA-associated redox abnormalities in the literature from 1981 to
      2010. Among 2170 journal articles on FA evaluated, 162 related FA with OS. Early
      studies reported excess oxygen toxicity in FA cells that accumulated oxidative
      DNA damage. Prooxidant states were found in white blood cells and body fluids
      from FA patients as excess luminol-dependent chemiluminescence, 8-hydroxy
      deoxyguanosine, reduced glutathione/oxidized glutathione imbalance, and tumour
      necrosis factor-alpha. Some FA gene products involved in redox homeostasis can be
      summarized as follows: (a) FANCA, FANCC, and FANCG interact with cytochrome P450
      related activities and/or respond to oxidative damage; (b) FANCD2 in OS response
      interacts with forkhead box O3 and ataxia telangiectasia mutated protein; (c)
      FANCG is found in mitochondria and interacts with PRDX3, and FA-G cells display
      distorted mitochondria and decreased peroxidase activity; (d) FANCJ (BACH1/BRIP1)
      is a repressor of haeme oxygenase-1 gene and senses oxidative base damage; (e)
      antioxidants, such as tempol and resveratrol decrease cancer incidence and
      haematopoietic defects in Fancd2(-/-) mice. The overall evidence for FA
      associated OS may suggest designing chemoprevention studies aimed at delaying the
      onset of OS-related clinical complications.

PMID- 22628296
TI  - Dye selection for live cell imaging of intact siRNA.
AB  - Investigations into the fate of small interfering RNA (siRNA) after transfection
      may unravel new ways to improve RNA interference (RNAi) efficiency. Because
      intracellular degradation of RNA may prevent reliable observation of fluorescence
      labeled siRNA, new tools for fluorescence microscopy are warranted to cover the
      considerable duration of the RNAi effect. Here, the characterization and
      application of new fluorescence resonance energy transfer (FRET) dye pairs for
      sensing the integrity of duplex siRNA is reported, which allows an assessment of
      the degradation status of an siRNA cell population by live cell imaging. A panel
      of high-yield fluorescent dyes has been investigated for their suitability as
      FRET pairs for the investigation of RNA inside the cell. Nine dyes in 13 FRET
      pairs were evaluated based on the performance in assays of photostability, cross
      excitation, bleed-through, as well as on quantified changes of fluorescence as a
      consequence of, e.g., RNA strand hybridization and pH variation. The
      Atto488/Atto590 FRET pair has been applied to live cell imaging, and has revealed
      first aspects of unusual trafficking of intact siRNA. A time-lapse study showed
      highly dynamic movement of siRNA in large perinuclear structures. These and the
      resulting optimized FRET labeled siRNA are expected to have significant impact on
      future observations of labeled RNAs in living cells.

PMID- 22628297
TI  - Reactive cysteine in the active-site motif of Bacteroides thetaiotaomicron
      dipeptidyl peptidase III is a regulatory residue for enzyme activity.
AB  - Dipeptidyl peptidase III (DPP III), a member of the metallopeptidase family M49,
      was considered as an exclusively eukaryotic enzyme involved in intracellular
      peptide catabolism and pain modulation. In 2003, new data on genome sequences
      revealed the first prokaryotic orthologs, which showed low sequence similarity to
      eukaryotic ones and a cysteine (Cys) residue in the zinc-binding motif HEXXGH.
      Here we report the cloning and heterologous expression of DPP III from the human
      gut symbiont Bacteroides thetaiotaomicron. The catalytic efficiency of bacterial
      DPP III for preferred synthetic substrate hydrolysis was very similar to that of
      the human host enzyme. Substitution of Cys450 from the active-site motif by
      serine did not substantially change the enzymatic activity. However, this residue
      was wholly responsible for the inactivation effect of sulfhydryl reagents.
      Molecular modeling indicated seven basic amino acid residues in the local
      environment of Cys450 as a possible cause for its high reactivity. Sequence
      analysis of 81 bacterial M49 peptidases showed conservation of the HECLGH motif
      in 68 primary structures with the majority of proteins lacking an active-site Cys
      originated from aerobic bacteria. Data obtained suggest that Cys450 of B.
      thetaiotaomicron DPP III is a regulatory residue for the enzyme activity.

PMID- 22628298
TI  - Proteome analysis of protein partners to nucleosomes containing canonical H2A or
      the variant histones H2A.Z or H2A.X.
AB  - Although the existence of histone variants has been known for quite some time,
      only recently are we grasping the breadth and diversity of the cellular processes
      in which they are involved. Of particular interest are the two variants of
      histone H2A, H2A.Z and H2A.X because of their roles in regulation of gene
      expression and in DNA double-strand break repair, respectively. We hypothesize
      that nucleosomes containing these variants may perform their distinct functions
      by interacting with different sets of proteins. Here, we present our proteome
      analysis aimed at identifying protein partners that interact with nucleosomes
      containing H2A.Z, H2A.X or their canonical H2A counterpart. Our development of a
      nucleosome-pull down assay and analysis of the recovered nucleosome-interacting
      proteins by mass spectrometry allowed us to directly compare nuclear partners of
      these variant-containing nucleosomes to those containing canonical H2A. To our
      knowledge, our data represent the first systematic analysis of the H2A.Z and
      H2A.X interactome in the context of nucleosome structure.

PMID- 22628299
TI  - Polyglutamine tracts as modulators of transcriptional activation from yeast to
      mammals.
AB  - Microsatellite repeats are genetically unstable and subject to expansion and
      shrinkage. A subset of them, triplet repeats, can occur within the coding region
      and specify homomeric tracts of amino acids. Polyglutamine (polyQ) tracts are
      enriched in eukaryotic regulatory proteins, notably transcription factors, and we
      had shown before that they can contribute to transcriptional activation in
      mammalian cells. Here we generalize this finding by also including evolutionarily
      divergent organisms, namely, Drosophila and baker's yeast. In all three systems,
      Gal4-based model transcription factors were more active if they harbored a polyQ
      tract, and the activity depended on the length of the tract. By contrast, a
      polyserine tract was inactive. PolyQs acted from either an internal or a C
      terminal position, thus ruling out a merely structural 'linker' effect. Finally,
      a two-hybrid assay in mammalian cells showed that polyQ tracts can interact with
      each other, supporting the concept that a polyQ-containing transcription factor
      can recruit other factors with polyQ tracts or glutamine-rich activation domains.
      The widespread occurrence of polyQ repeats in regulatory proteins suggests a
      beneficial role; in addition to the contribution to transcriptional activity,
      their genetic instability might help a species to adapt to changing environmental
      conditions in a potentially reversible manner.

PMID- 22628300
TI  - (99m)Tc(CO)(3)-Ibritumomab tiuxetan; a novel radioimmunoimaging (RII) agent of B
      cell non-Hodgkin's lymphoma (NHL).
AB  - To exploit the B-lymphocyte antigen-CD20 binding capacity of the Ibritumomab
      tiuxetan (IBTN) monoclonal antibody (mAb) for imaging, the over-expression of B
      cells in non-Hodgkin's lymphoma (NHL) (a myeloproliferative disorder of the
      lymphatic system) was investigated. In the current investigation, we present the
      labeling of the IBTN with technetium-99m ((99m)Tc) through [(99m)Tc(CO)(3)](+)
      precursor for radioimmunoimaging (RII) of the tumor prior to its treatment with
      (90)Y labeled IBTN. Labeled IBTN was radiobiologically characterized in terms of
      radiochemical purity, in vitro stability in human plasma, immunoreactivity,
      binding with Raji and Ramos cells and biodistribution in a female nude mouse
      (FNM) model. It was observed that the reduced IBTN (rIBTN) showed more promising
      radiobiologic characteristics than the nonreduced IBTN. Significantly higher
      transchelation was seen in excess cysteine compared with histidine. The
      radioconjugate showed higher saturated binding affinity with CD20 antigen.
      Significantly higher target (tumor) to background ratios were observed 1 h post
      injection (p.i.). Based on radiochemical purity, in vitro stability,
      immunoreactivity, binding and biodistrubtion in the FNM model, we recommend the
      radiolabeling of the rIBTN using tricarbonyl technique as a potential RII agent.

PMID- 22628301
TI  - Protection from Clostridium difficile toxin B-catalysed Rac1/Cdc42 glucosylation
      by tauroursodeoxycholic acid-induced Rac1/Cdc42 phosphorylation.
AB  - Toxin A (TcdA) and toxin B (TcdB) are the major virulence factors of Clostridium
      difficile-associated diarrhoea (CDAD). TcdA and TcdB mono-glucosylate small
      GTPases of the Rho family, thereby causing actin re-organisation in colonocytes,
      resulting in the loss of colonic barrier function. The hydrophilic bile acid
      tauroursodeoxycholic acid (TUDCA) is an approved drug for the treatment of
      cholestasis and biliary cirrhosis. In this study, TUDCA-induced activation of
      Akt1 is presented to increase cellular levels of pS71-Rac1/Cdc42 in human
      hepatocarcinoma (HepG2) cells, showing for the first time that bile acid
      signalling affects the activity of Rho proteins. Rac1/Cdc42 phosphorylation, in
      turn, protects Rac1/Cdc42 from TcdB-catalysed glucosylation and reduces the TcdB
      induced cytopathic effects in HepG2 cells. The results of this study indicate
      that TUDCA may prove useful as a therapeutic agent for the treatment of CDAD.

PMID- 22628302
TI  - Oleic acid is a key cytotoxic component of HAMLET-like complexes.
AB  - HAMLET is a complex of alpha-lactalbumin (alpha-LA) with oleic acid (OA) that
      selectively kills tumor cells and Streptococcus pneumoniae. To assess the
      contribution of the proteinaceous component to cytotoxicity of HAMLET, OA
      complexes with proteins structurally and functionally distinct from alpha-LA were
      prepared. Similar to HAMLET, the OA complexes with bovine beta-lactoglobulin
      (bLG) and pike parvalbumin (pPA) (bLG-OA-45 and pPA-OA-45, respectively) induced
      S. pneumoniae D39 cell death. The activation mechanisms of S. pneumoniae death
      for these complexes were analogous to those for HAMLET, and the cytotoxicity of
      the complexes increased with OA content in the preparations. The half-maximal
      inhibitory concentration for HEp-2 cells linearly decreased with rise in OA
      content in the preparations, and OA concentration in the preparations causing HEp
      2 cell death was close to the cytotoxicity of OA alone. Hence, the cytotoxic
      action of these complexes against HEp-2 cells is induced mostly by OA. Thermal
      stabilization of bLG upon association with OA implies that cytotoxicity of bLG-OA
      45 complex cannot be ascribed to molten globule-like conformation of the protein
      component. Overall, the proteinaceous component of HAMLET-like complexes studied
      is not a prerequisite for their activity; the cytotoxicity of these complexes is
      mostly due to the action of OA.

PMID- 22628303
TI  - Identification of ATF2 as a transcriptional regulator of renin gene.
AB  - The cAMP response element (enhCRE) in the distal enhancer regulatory region of
      renin gene is believed to play a major role in the control of renin
      transcription. enhCRE binds the CRE-binding protein (CREB), which is the main
      transcription factor target of cAMP signaling. Using the mouse renin-producing
      cell line As4.1 we found that activating transcription factor-2 (ATF2) also binds
      to enhCRE. N-terminal phosphorylation of ATF2, which controls its
      transactivation, is associated with downregulation of renin gene expression by
      the cytokine tumor necrosis factor-alpha (TNFalpha). The ubiquitin proteasome
      inhibitor MG132 also phosphorylates ATF2 and inhibits renin expression. Knockdown
      of ATF2 attenuated the suppression of renin gene expression by MG132, thus
      demonstrating that ATF2 mediates the inhibitory effect of MG132. In addition,
      MG132 increased the DNA-binding of ATF2 as well as the ratio of bound ATF2 to
      CREB. Using ATF2- and CREB-Gal4 fusion protein constructs coupled with luciferase
      reporter system we showed that ATF2 has a weaker transactivating capacity than
      CREB. These data suggest that ATF2 represses renin expression by drifting the
      transcriptional control of renin gene away from CREB. Accordingly, TNFalpha
      completely abrogated the cAMP-dependent stimulation of renin gene expression.

PMID- 22628304
TI  - A novel role for reciprocal CD30-CD30L signaling in the cross-talk between
      natural killer and dendritic cells.
AB  - The interplay between dendritic cells (DCs) and natural killer (NK) cells directs
      adaptive immune responses. The molecular basis of the cross-talk is largely
      undefined. Here, we provide evidence for a contribution of CD30 (TNFRSF8) and its
      ligand CD30L (TNFSF8) expressed on NK cells and DCs, respectively. We demonstrate
      that CD30-mediated engagement of CD30L induced cytokine secretion from immature
      DCs via the mitogen-activated protein kinase pathway. Moreover, CD30L engagement
      promoted differentiation to mature DCs. On the contrary, the engagement of CD30
      on NK cells resulted in an NF-kappaB-dependent release of TNF-alpha/IFN-gamma.
      These data uncover a novel and unexpected role for CD30/CD30L that contributes to
      proinflammatory immune responses.

PMID- 22628305
TI  - Mast cells express tyrosine hydroxylase and store dopamine in a serglycin
      dependent manner.
AB  - Here we show that mast cells contain dopamine and that mast cell activation
      causes dopamine depletion, indicating its presence within secretory granules.
      Dopamine storage increased during mast cell maturation from bone marrow
      precursors, and was dependent on the presence of serglycin. Moreover, the
      expression of tyrosine hydroxylase, the key enzyme in dopamine biosynthesis, was
      induced during mast cell maturation; histidine decarboxylase and tryptophan
      hydroxylase 1 were also induced. Mast cell activation caused a robust induction
      of histidine decarboxylase, but no stimulation of tyrosine hydroxylase or
      tryptophan hydroxylase 1 expression. The present study points toward a possible
      role of dopamine in mast cell function.

PMID- 22628306
TI  - The critical role of adrenomedullin and its binding protein, AMBP-1, in
      neuroprotection.
AB  - Chronic neurodegenerative disorders and acute injuries of the central nervous
      system exert a prohibitive economic burden, which is aggravated by an unmet
      medical need for the development of effective neurotherapeutics. The
      evolutionarily conserved neuropeptide, adrenomedullin (AM), and its binding
      protein, AMBP-1, also known as complement factor H, play important roles in brain
      physiology, and their expression is altered in brain pathology. In this review,
      we discuss the molecular regulation of AM and AMBP-1 and the pivotal roles they
      play in neuroprotection following brain injury. We assess the reciprocal
      synergistic effects of AM and AMBP-1 and make suggestions for the design of a
      novel combination neurotherapy devoid of the potential hypotensive effects of AM
      while optimizing its neuroprotective property.

PMID- 22628307
TI  - Ubiquilins in the crosstalk among proteolytic pathways.
AB  - Protein degradation occurs through several distinct proteolytic pathways for
      membrane and cytosolic proteins. There is evidence that these processes are
      linked and that crosstalk among these major protein degradation pathways occurs.
      Ubiquilins, a family of ubiquitin-binding proteins, are involved in all protein
      degradation pathways. This minireview provides an overview of ubiquilin function
      in protein degradation and contrasts it with sequestosome-1 (p62), a protein that
      also has been implicated in multiple proteolytic pathways.

PMID- 22628308
TI  - A non-cytotoxic but ribonucleolytically specific ribotoxin variant: implication
      of tryptophan residues in the cytotoxicity of hirsutellin A.
AB  - Ribotoxins are a family of toxic proteins that exert a highly specific cleavage
      at the universally conserved sarcin/ricin loop (SRL) of the larger rRNA molecule.
      Before this ribonucleolytic action, passage through the cell membrane is a
      necessary step for ribotoxin internalization and the limiting factor for
      cytotoxicity. Although extensive knowledge of their ribonucleolytic activity and
      substrate recognition has been accumulated, little is known about the mechanisms
      of cell entry of ribotoxins. Hirsutellin A (HtA) is a recently described member
      of this family, which accommodates the main abilities of previously characterized
      ribotoxins into a shorter sequence, but exhibits some differences regarding
      membrane interaction properties. This work investigates the contribution of
      tryptophan (Trp) residues 71 and 78 to both endoribonucleolytic activity and
      cellular toxicity of this ribotoxin. Substitution mutants W71F and W78F, as well
      as the double mutant W71/78F, were obtained and assayed against isolated
      ribosomes, synthetic SRL, and human tumor cells. The results provide evidence
      that cell membrane passage and internalization, as well as substrate-specific
      recognition, require the participation of the region involving both Trp 71 and
      Trp 78. Additionally, the mutant W71/78F is the first non-cytotoxic but specific
      ribosome-cleaving ribotoxin mutant obtained to date.

PMID- 22628309
TI  - The composite nature of the interaction between nuclear receptors EcR and DHR38.
AB  - Ecdysteroids coordinate essential biological processes in Drosophila through a
      complex of two nuclear receptors, the ecdysteroid receptor (EcR) and the
      ultraspiracle protein (Usp). Biochemical experiments have shown that, in contrast
      to Usp, the EcR molecule is characterized by high intramolecular plasticity. To
      investigate whether this plasticity is sufficient to form EcR complexes with
      nuclear receptors other than Usp, we studied the interaction of EcR with the
      DHR38 nuclear receptor. Previous in vitro experiments suggested that DHR38 can
      form complexes with Usp and thus disrupt Usp-EcR interaction with the specific
      hsp27pal response element. This article provides the experimental evidence that
      EcR is able to form complexes with DHR38 as well. The recombinant DNA-binding
      domains (DBDs) of EcR and DHR38 interact specifically on hsp27pal. However, the
      interaction between the receptors is not restricted to their isolated DBDs. We
      pre?xadsent data that indicate that the full-length EcR and DHR38 can also form
      specific complexes within the nuclei of living cells. This interaction is
      mediated by the hinge region of EcR, which was recently classified as an
      intrinsically disordered region. Our results indicate that DHR38 might modulate
      the activity of the Usp-EcR heterodimer by forming complexes with both of its
      components.

PMID- 22628310
TI  - Tmem27 dimerization, deglycosylation, plasma membrane depletion, and the
      extracellular Phe-Phe motif are negative regulators of cleavage by Bace2.
AB  - The pancreatic beta-cell surface protein Tmem27 is promotes the preservation of
      functional beta-cell mass. It is a selective substrate of the protease Bace2, yet
      the intramolecular features of Tmem27 that regulate its processing by this
      sheddase have not been characterized. In particular, the importance of
      homodimerization, glycosylation, trafficking to the plasma membrane (PM), the
      existence of multiple cleavage sites, and the amino acid residues that govern
      these features are currently unknown. Using Tmem27 mutational analysis and
      multiple biochemical approaches, we here show that Tmem27 dimerization is a
      dynamic process mediated by its intracellular cysteine residue and that prevents
      Tmem27 cleavage, that extracellular asparagine glycosylation is essential for
      Tmem27 trafficking to the PM and its processing by Bace2, that the amount of
      Tmem27 at the PM is proportional to its total cell levels upon glucose
      stimulation and Bace2 inhibition, and that the double phenylalanine motif in the
      Tmem27 cleavage site is an intramolecular Bace2 inhibitor. These findings define
      structural properties of Tmem27 that affect the susceptibility to its protease
      Bace2 and have implications for the efficiency with which Tmem27 and other Bace2
      substrates are cleaved in normal and disease states.

PMID- 22628311
TI  - New ketomethylene inhibitor analogues: synthesis and assessment of structural
      determinants for N-domain selective inhibition of angiotensin-converting enzyme.
AB  - Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase containing two
      homologous domains. While the C-domain plays a major role in blood pressure
      regulation, the N-domain hydrolyzes the antifibrotic agent N-acetyl-Ser-Asp-Lys
      Pro. Thus, N-domain selective (N-selective) inhibitors could be useful in the
      treatment of conditions relating to excessive tissue fibrosis. New keto-ACE
      analogues were designed that contained functionalities considered important for N
      selective inhibitor RXP407 binding, namely, a P(2) Asp, N-acetyl group, and C
      terminal amide. Such functionalities were incorporated to assess the structural
      determinants for N-selective binding in a novel inhibitor template. Inhibitors
      containing a C-terminal amide and modified P(2)' group were poor inhibitors of
      the N-domain, with several of these displaying improved inhibition of the C
      domain. Molecules with both a C-terminal amide and P(2) Asp were also poor
      inhibitors and not N-selective. Compounds containing a free C-terminus, a P(2)
      Asp and protecting group displayed a change of more than 1000-fold N-selectivity
      compared with the parent molecule. Molecular docking models revealed interaction
      of these P(2) groups with S(2) residues Tyr369 and Arg381. This study emphasizes
      the importance of P(2) functionalities in allowing for improved N-selective
      binding and provides further rationale for the design of N-selective inhibitors,
      which could be useful in treating tissue fibrosis.

PMID- 22628312
TI  - Cadherin-related protein 24 induces morphological changes and partial cell
      polarization by facilitating direct cell-cell interactions.
AB  - Cadherin-related protein 24 (CDHR24) is a potential tumor suppressor located
      apically as well as laterally in polarized cells. Here, the role of CDHR24 in
      contributing to cell morphology and polarity is examined. CDHR24 was
      predominantly localized at the nonattached part of nonpolarizing cells while
      another apically sorted protein, aminopeptidase N, was equally distributed over
      the plasma membrane. Furthermore, CDHR24 expression induced cell aggregation
      capacity, indicating direct cell-cell interaction. The transepithelial
      resistance, however, was elevated in polarized MDCK cells, but not in
      nonpolarizing CHO cells. Our data propose a model in which CDHR24 is directly
      involved in cell and tissue morphogenesis.

PMID- 22628313
TI  - Analysis of tissue and salivary nicotinamide N-methyltransferase in oral squamous
      cell carcinoma: basis for the development of a noninvasive diagnostic test for
      early-stage disease.
AB  - Oral squamous cell carcinoma (OSCC) is the most common form of head and neck
      cancer worldwide. In recent decades, the 5-year mortality rate is approximately
      50% around the world. As reliable biomarkers of oral cancer are still lacking, it
      is necessary to identify new target molecules for early diagnosis, effective
      therapy, and monitoring of the disease. In the present work, we focused on the
      expression of the enzyme nicotinamide N-methyltransferase (NNMT). We analyzed
      enzyme activity in 37 paired tumor and non-tumor tissues and found that activity
      levels are significantly higher in tumor compared with adjacent normal oral
      mucosa. Interestingly, oral epithelium surrounding tumor of unfavorable cases
      (N+) seems to display higher activity levels compared with that of favorable ones
      (N0). Western blot analyses were performed to evaluate protein levels in saliva
      samples from patients with OSCC and healthy subjects. Preliminary results
      indicated an up-regulation of salivary NNMT in tumor. This study shows a marked
      increase in enzyme activity in oral cancer and suggests that adjacent normal
      tissue of unfavorable cases seems to change toward cancer. Moreover, it is
      conceivable to hypothesize that NNMT could represent a potential biomarker for
      early and non-invasive diagnosis of oral cancer.

PMID- 22628314
TI  - Mitochondrial protein import pathways are functionally conserved among eukaryotes
      despite compositional diversity of the import machineries.
AB  - Mitochondrial protein import (MPI) is essential for the biogenesis of
      mitochondria in all eukaryotes. Current models of MPI are predominantly based on
      experiments with one group of eukaryotes, the opisthokonts. Although fascinating
      genome database-driven hypotheses on the evolution of the MPI machineries have
      been published, previous experimental research on non-opisthokonts usually
      focused on the analysis of single pathways or components in, for example, plants
      and parasites. In this study, we have established the kinetoplastid parasite
      Leishmania tarentolae as a model organism for the comprehensive analysis of non
      opisthokont MPI into all four mitochondrial compartments. We found that
      opisthokont marker proteins are efficiently imported into isolated L. tarentolae
      mitochondria. Vice versa, L. tarentolae marker proteins of all compartments are
      also imported into mitochondria from yeast. The results are remarkable because
      only a few of the more than 25 classical components of the opisthokont MPI
      machineries are found in parasite genome databases. Our results demonstrate that
      different MPI pathways are functionally conserved among eukaryotes despite
      significant compositional differences of the MPI machineries. Moreover, our model
      system could lead to the identification of significantly altered or even novel
      MPI components in non-opisthokonts. Such differences might serve as starting
      points for drug development against parasitic protists.

PMID- 22628315
TI  - Small molecule inhibitors of the c-Jun N-terminal kinase (JNK) possess antiviral
      activity against highly pathogenic avian and human pandemic influenza A viruses.
AB  - C-Jun N-terminal kinases (JNK) are activated in course of many viral infections.
      Here we analyzed the activity of JNK inhibitors on influenza A virus (IAV)
      amplification. Human lung epithelial cells were infected with either the highly
      pathogenic avian virus strain A/FPV/Bratislava/79 (H7N7) or the pandemic swine
      origin influenza virus A/Hamburg/4/09 (H1N1v). The application of the JNK
      inhibitors SP600125 and AS601245 reduced IAV amplification by suppressing viral
      protein and RNA synthesis. Although AS601245 appeared to generally block the
      transcription of newly introduced genes, SP600125 specifically affected viral RNA
      synthesis. Overexpression of a dominant negative mutant of SEK/MKK4 and siRNA
      mediated suppression of JNK2 expression confirmed that specific manipulation of
      the JNK pathway attenuates virus propagation. An IAV minigenome replication assay
      revealed that SP600125 did not directly affect the activity of the viral RNA
      polymerase complex but seems to suppress an anti-influenza nonstructural protein
      1-mediated virus supportive function. Finally, when H7N7- or H1N1v-infected mice
      were treated with SP600125, the viral load is reduced in lungs of treated
      compared with untreated mice. Our data suggest that this class of ATP competitive
      inhibitors once optimized for antiviral action potentially represent novel drugs
      for antiviral intervention.

PMID- 22628316
TI  - Matriptase-2 (TMPRSS6) is directly up-regulated by hypoxia inducible factor-1:
      identification of a hypoxia-responsive element in the TMPRSS6 promoter region.
AB  - The type II transmembrane serine protease matriptase-2 (TMPRSS6) down-regulates
      the expression of hepcidin, the main regulator of systemic iron homeostasis, and
      increases in this way iron plasma levels. Matriptase-2 is up-regulated under
      hypoxic conditions, providing a new link between hypoxia signaling and iron
      homeostasis. In this study, we have characterized the TMPRSS6 promoter region and
      identified a functional hypoxia-responsive element (HRE). Mutations of the
      hypoxia inducible factor (HIF)-binding site located within the HRE abrogate HIF
      1alpha-dependent induction of TMPRSS6 expression. The action of HIF-1alpha on
      TMPRSS6 promoter activity reveals a new regulative element for the suppression of
      hepcidin synthesis.

PMID- 22628317
TI  - Rab1 interacts directly with the beta2-adrenergic receptor to regulate receptor
      anterograde trafficking.
AB  - Very little is understood about the trafficking of G protein-coupled receptors
      (GPCRs) from the endoplasmic reticulum (ER) to the plasma membrane. Rab guanosine
      triphosphatases (GTPases) are known to participate in the trafficking of various
      GPCRs via a direct interaction during the endocytic pathway, but whether this
      occurs in the anterograde pathway is unknown. We evaluated the potential
      interaction of Rab1, a GTPase known to regulate beta2-adrenergic receptor
      (beta2AR) trafficking, and its effect on export from the ER. Our results show
      that GTP-bound Rab1 interacts with the F(x)(6)LL motif of beta2AR. Receptors
      lacking the interaction motif fail to traffic properly, suggesting that a direct
      interaction with Rab1 is required for beta2AR anterograde trafficking.

PMID- 22628318
TI  - Obtaining reference intervals traceable to reference measurement systems: is it
      possible, who is responsible, what is the strategy?
AB  - An issue associated with standardization efforts is the need to develop useful
      reference intervals (RI). Lack of proper RI may hamper the implementation of
      standardization in Laboratory Medicine as standardization can modify analyte
      results and, without adequate RI, this can impair the result interpretation. Once
      defined, RI obtained with analytical procedures that produce results traceable to
      the corresponding reference system can be transferred among laboratories,
      providing that they use commercial assays that produce results traceable to the
      same reference system and populations have the same characteristics. Multicenter
      studies are needed for a robust definition of traceable RI, using experimental
      protocols that include well defined prerequisites. Particularly, employed methods
      must produce results that are traceable to the reference system for that specific
      analyte. Thus, the trueness of laboratories producing reference values should be
      verified and, if necessary, experimental results corrected in accordance with
      correlation results with the selected reference. If requirements in the adoption
      of traceable RI are fulfilled, the possibility of providing RI that are
      applicable to any laboratory, able to produce results traceable to the reference
      system, is realistic. The definition of traceable RI should hopefully cause the
      disappearance of different RI employed for the same analyte, providing more
      effective information to clinicians.

PMID- 22628319
TI  - Analytical performance, reference values and decision limits. A need to
      differentiate between reference intervals and decision limits and to define
      analytical quality specifications.
AB  - With the increasing use of decision limits (action limits, cut-off points)
      specified for a number of analytical components in diagnosis and for action in
      critical situations, formulated in national or international recommendations, the
      traditional interpretation of reference intervals has been uncertain, and
      sometimes the two concepts are being mixed up by incorporating risk calculations
      in the reference intervals. There is, therefore, a need to clarify the two
      concepts and to keep them definitely separated. Reference intervals are the 95%
      limits for the descriptions of the distributions of the values of analytical
      components measured on reference samples from reference individuals. Decision
      limits are based on guidelines from national and international expert groups
      defining specific concentrations of certain components as limits for decision
      about diagnosis or well-defined specific actions. Analytical quality
      specifications for reference intervals have been defined for bias since the
      1990s, but in the recommendations specified in the clinical guidelines analytical
      quality specifications are only scarcely defined. The demands for negligible
      biases are, however, even more essential for decision limits, as the choice is no
      longer left to the clinician, but emerge directly from the concentration. Even a
      small bias will change the number of diseased individuals, so the demands for
      negligible biases are obvious. A view over the analytical quality as published
      gives a variable picture of bias for many components, but with many examples of
      considerable bias which must be critical--yet no specifications have been
      stipulated until now.

PMID- 22628320
TI  - Disadvantages of using biological variation data for reference change values.

PMID- 22628321
TI  - Insulin-like growth factor 1 reference intervals for a chemiluminescent enzyme
      immunometric assay (Immulite 2000(r)) in an adult Mediterranean population.

PMID- 22628322
TI  - Reference values and the journal: why the past is now present.

PMID- 22628323
TI  - Other-than-annual variations in morning determinations of uric acid.

PMID- 22628324
TI  - Blood biochemical markers of bone turnover: pre-analytical and technical aspects
      of sample collection and handling.
AB  - Casual or systematic errors occurring in pre-analytical, analytical or post
      analytical phases influence laboratory test results. The areas where pre
      analytical phase errors most often arise are: timing of specimen collection;
      selection of specimen type; and time and temperature of storage/transport. Bone
      turnover markers are clinically useful in evaluating bone metabolism. Although
      unquestionably valuable tools, little is known about the pre-analytical
      precautions for their correct use and there is no consensus on kind of sample, or
      storage time and temperature before analysis. Moreover, biological variability,
      because of uncontrollable and controllable factors, will affect pre-analytical
      variability. Serum should be preferred to simplify blood drawing; therefore, only
      one tube should be used for the analysis of all bone markers. Short-term storage
      at 4 degrees C may be advisable to preserve stability, immediate storage at -70
      degrees C is recommended for longer periods, while avoiding repeated freeze
      thawing cycles. Sampling should be performed in the morning in fasting subjects
      who have abstained from physical exercise for 24 h. This review aimed to give a
      knowledge update on pre-analytical phase precautions in performing bone turnover
      marker measurement.

PMID- 22628325
TI  - A comprehensive review of upper reference limits reported for (high-)sensitivity
      cardiac troponin assays: the challenges that lie ahead.
AB  - Cardiac troponins (cTn) are the preferred markers for the diagnosis of acute
      myocardial infarction (AMI). The guidelines recommend the use of the 99th
      percentile upper reference concentration of a healthy population as the
      diagnostic cut-off for AMI. However, a broad range of upper reference limits is
      still employed, complicating the diagnosis of AMI. This overview is meant to
      assist laboratory specialists to define an appropriate cut-off value for the
      diagnosis of AMI. Therefore, we provide an overview of the analytical performance
      and upper reference limits of seven (high-)sensitivity cTn assays: Roche high
      sensitivity cTnT and ADVIA Centaur, Stratus CS, Dimension Vista, Vitros ECi,
      Access and Architect cTnI assays. It is shown that none of the reference
      populations completely met the guidelines, including those in package inserts.
      Forty percent of the studies collected less than the advised minimum of 300
      subjects. Many studies (50%) did not report their inclusion criteria, while lower
      99th percentile limits were observed when more stringent selection criteria were
      applied. Higher troponin cut-offs were found in men and elderly subjects,
      suggesting sex- and age-specific cut-offs would be considered. Therefore, there
      is still need for a large, rigorously screened reference population to more
      accurately establish cTn upper reference limits.

PMID- 22628326
TI  - A pragmatic proposal for permissible limits in external quality assessment
      schemes with a compromise between biological variation and the state of the art.
AB  - Permissible limits for internal and external quality assurance are either based
      on biological variation or on the state of the art (technical feasibility). The
      former approach has a scientific basis, but, in some cases, leads to limits which
      are either not achievable under the present technology, or which are not
      stringent enough. If proficiency testing is mandatory, stringent limits which
      cannot be fulfilled by the majority of laboratories could lead to juristic
      consequences. Therefore, most national guidelines were based on the state of the
      art, however, without providing the underlying reasoning. A simple algorithm for
      permissible limits in external quality assessment schemes (EQAS) is proposed
      based on biological variation, technical feasibility and correlated to the rate
      of false positive results. The proposed limits are compared with some limits from
      several EQAS (RiliBAK, SEKK, RCPA, CLIA, PROLARIT). The suggested limits are
      slightly more stringent than the German RiliBAK, less stringent than the
      Australasian guidelines and agreed best with the Czech SEKK and the Italian
      PROLARIT scheme. The graphical presentation of permissible limits strictly
      derived of biological variation with the proposed limits led to straight lines
      with different slopes and a cross-over at the limits for quantities with a medium
      biological variation (e.g., trijodthyronine). The greatest discordance between
      the various recommendations was observed for calcium, chloride, hemoglobin A(1c)
      and sodium.

PMID- 22628327
TI  - Age dependence of within-subject biological variation of nine common clinical
      chemistry analytes.
AB  - BACKGROUND: The knowledge of biological variation (BV) data is important for
      clinical decisions and as a basis for defining analytical quality specifications.
      However, in generating reliable data of biological variation there are still some
      unsolved problems, such as age dependence. The aim of our work is to verify this
      aspect. METHODS: Twenty-six subjects divided into three groups by age were
      studied. Blood samples were collected in lithium heparin tubes for four weeks at
      one week intervals, on the same day of the week (Tuesday) and at the same time of
      day (8-9 a.m.) by the same phlebotomist. They were analysed in duplicate for
      creatinine, urate, calcium, albumin, total cholesterol, high density lipoprotein
      (HDL) and low density lipoprotein (LDL)-cholesterol, triglycerides and iron.
      After outlier exclusion by Cochran's test, components of biological variation
      were calculated by ANOVA. The significance of the differences between results of
      the classes was also calculated with the Student's test (t-test) and the Fisher's
      test (F-test). RESULTS: Excluding albumin, the group 3 results (age range from 78
      to 98 years) showed significantly lower CV within subjects (CV(W)) than the other
      two groups. CONCLUSIONS: Our data seem to highlight the relevance of the age when
      choosing the reference subjects for biological variation studies. The level of
      within-subject biological variation of the elderly group may have been further
      reduced by the homogeneity of the group constituted by individuals living
      together in the same nursing home.

PMID- 22628328
TI  - Population-based pediatric reference intervals for general clinical chemistry
      analytes on the Abbott Architect ci8200 instrument.
AB  - BACKGROUND: Reference intervals are crucial decision-making tools aiding
      clinicians in differentiating between healthy and diseased populations. However,
      for children such values often are lacking or incomplete. METHODS: Blood samples
      were obtained from 692 healthy children, aged 6 months to 18 years, recruited in
      daycare centers and schools. Twelve common general clinical chemistry analytes
      were measured on the Abbott Architect ci8200 platform; sodium, potassium,
      chloride, calcium, albumin-adjusted calcium, phosphate, magnesium, creatinine
      (Jaffe and enzymatic), cystatin C, urea and uric acid. RESULTS: Age- and gender
      specific pediatric reference intervals were defined by calculating the 2.5th and
      97.5th percentiles. CONCLUSIONS: The data generated is primarily applicable to a
      Caucasian population when using the Abbott Architect platform, but could be used
      by any laboratory if validated for the local patient population.

PMID- 22628329
TI  - Uric acid biorhythm, a feature of long-term variation in a clinical laboratory
      database.
AB  - BACKGROUND: The biorhythm of serum uric acid was evaluated in a large sample of a
      clinical laboratory database by spectral analysis and the influence of the gender
      and age on uric acid variability. METHODS: Serum uric acid values were extracted
      from a large database of a clinical laboratory from May 2000 to August 2006.
      Outlier values were excluded from the analysis and the remaining data (n=73,925)
      were grouped by gender and age ranges. Rhythm components were obtained by the
      Lomb Scargle method and Cosinor analysis. RESULTS: Serum uric acid was higher in
      men than in women older than 13 years (p<0.05). Compared with 0-12 year group,
      uric acid increased in men but not in women older than 13 years (p<0.05).
      Circannual (12 months) and transyear (17 months) rhythm components were detected,
      but they were significant only in adult individuals (>26 years, p<0.05). Cosinor
      analysis showed that midline estimating statistic of rhythm (MESOR) values were
      higher in men (range: 353-368 MUmol/L) than in women (range: 240-278 MUmol/L;
      p<0.05), independent of the age and rhythm component. The extent of predictable
      change within a cycle, approximated by the double amplitude, represented up to
      20% of the corresponding MESOR. CONCLUSIONS: Serum uric acid biorhythm is
      dependent on gender and age and it may have relevant influence on preanalytical
      variability of clinical laboratory results.

PMID- 22628330
TI  - Age-related changes in serum amino acids concentrations in healthy individuals.
AB  - BACKGROUND: Serum amino acids, part of a pool of free amino acids, are influenced
      by metabolism and disease. Few reports exist describing their function and
      concentrations in serum. Our study aimed to determine age- and gender-related
      differences in serum amino acid concentrations in healthy Japanese patients,
      focusing on their inclusion in body proteins. METHODS: Healthy patients with
      normal liver and kidney function were selected based on biochemical variables.
      Serum amino acid concentrations in 23-88-year-old patients (312 males, 252
      females; 52.1+/-15.0 years) were evaluated to determine the normal values and to
      clarify the differences in concentration. The patients were divided into 11
      groups according to their gender and age (in 5-year increments), and serum amino
      acid concentrations were determined as the normal values for each group. RESULTS:
      Some amino acids increased or decreased with age. Values of leucine, threonine,
      methionine, histidine, glycine, serine and taurine decreased with age in males,
      whereas, those of threonine and serine decreased with age in females (p<0.05). In
      contrast, values of phenylalanine, aspartate, asparagine, glutamate, alanine,
      citrulline, ornithine, arginine and tyrosine increased with age in males,
      whereas, values of phenylalanine, lysine, asparagine, glutamate, glutamine,
      alanine, citrulline, ornithine, arginine, tyrosine and proline increased with age
      in females (p<0.05). CONCLUSIONS: We clarified basic trends of age- and gender
      related amino acid concentrations in serum. In normal healthy Japanese people who
      ate normally and lived an independent life, there are significant age- and gender
      related differences.

PMID- 22628331
TI  - Characterisation of a highly sensitive troponin I assay and its application to a
      cardio-healthy population.
AB  - BACKGROUND: Abbott Diagnostics have developed a new highly sensitive troponin I
      (hs-TnI) assay. We have assessed its analytical characteristics and applied the
      assay to a population of apparently cardio-healthy persons. METHODS: We assessed
      imprecision, bias compared to the previous generation assay, matrix effects, and
      interferences and applied the assay to an apparently healthy population, deriving
      the 99th percentile limit of the distribution of values in reference populations
      for men and women separately. RESULTS: The dynamic range of the assay was ranged
      from 0.5-50,000 ng/L (pg/mL). The 10% CV was at a concentration of 3.9 ng/L, and
      the 20% CV was at a concentration of 1.8 ng/L. The new and current version of the
      TnI assay were highly correlated [slope: 0.98 (95%CI:0.88-1.07), y-intercept:1.20
      (95%CI:-2.35-4.75) r2=0.99]. The 99th percentile limit of the distribution of
      values in a reference population was different for males and females: for males
      14.0 ng/L and for females 11.1 ng/L and at these concentrations the assay CV was
      5.0%. TnI was detectable in nearly all patient samples from the healthy reference
      population (98.6%). CONCLUSIONS: This new hs-TnI assay is able to measure to an
      order of magnitude lower than the current generation TnI assay from the same
      manufacturer. With TnI being detectable in nearly all apparently healthy subject
      samples this suggests that TnI presence does not always indicate cardiomyocyte
      necrosis.

PMID- 22628332
TI  - Age-specific thyroid hormone and thyrotropin reference intervals for a pediatric
      and adolescent population.
AB  - BACKGROUND: Establishment of reliable reference intervals remains valuable for
      confirming validity and advancing standardization across methods and populations.
      Moreover, knowledge of the measurement uncertainty (U) and of the reference
      change value (RCV) has important applications in clinical chemistry. METHODS:
      Starting from the information available in the laboratory data base (29,901
      subjects) an initial selection was carried out by eliminating all subjects with a
      clinical or laboratory pathological report; data from 7581 0- to 20-year-old
      subjects (53.87% girls) remained in the study. These subjects, divided into nine
      age groups, were used to define reference distribution percentiles (2.5th, 50th
      and 97.5th) of serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4),
      and free T4 (fT4), as well as U and RCV of these assays. RESULTS: In early
      infancy, T4 and fT4 values were higher than in the older age groups. Serum T4
      95th percentile reference value, useful for the diagnosis of hyperthyroidism, was
      142.9 in 20-year-old boys and 230.4 nmol/L in early infants and serum T3 95th
      percentile was 2.6 and 3.5 nmol/L, respectively, while fT4 2.5th percentile
      reference value, useful for the diagnosis of hypothyroidism, was 9.6 and 13.0
      pmol/L, respectively. Serum TSH 97.5th percentile showed less age variation, 4.38
      4.88 mIU/L. Performance of the four assays resulted in approximately 20% Us,
      reflecting simple and complex imprecision, trueness, analytical and functional
      sensitivity. RCV of serum TSH (58.6%) was larger than for thyroid hormones (28.3%
      34.7%), probably due to the high biological variation of this hormone.
      CONCLUSIONS: We have established reference interval for TSH and thyroid hormones,
      as well as Us for assessing reliability of measurements, and RCVs to alert users
      on the presence of clinical significant changes.

PMID- 22628333
TI  - Serum thyroglobulin reference values according to NACB criteria in healthy
      subjects with normal thyroid ultrasound.
AB  - BACKGROUND: The present study was undertaken to establish serum thyroglobulin
      (Tg) normal reference values in a large group of healthy subjects. METHODS: Four
      hundred and thirty-eight non-smoking healthy subjects were selected to assess the
      Tg reference values (209 males, 229 non-pregnant females, age 34.7+/-13.1 years).
      Inclusion criteria were: no personal or familial history of thyroid disease,
      thyrotropin levels from 0.5 to 2.00 mUI/L, negative thyroperoxidase and
      thyroglobulin antibodies. In addition, the patients had a normal size thyroid
      (females <=18 mL, males <=25 mL) without nodules on the thyroid ultrasound (TUS).
      According to National Academy of Clinical Biochemistry (NACB) criteria the Tg
      results were transformed to a logarithmic scale and reference ranges were
      calculated as mean+/-2 SD. RESULTS: Serum Tg was measured on the Beckman Coulter
      UniCel DxI 800 automated platform by the simultaneous 1-step immunoenzymatic
      Access Thyroglobulin assay (Beckmann-Coulter SA, Nyon, Switzerland). Serum Tg
      levels were higher in females than in males (p=0.0022). Accordingly, gender
      specific reference values were calculated (i.e., males: 1.40-29.2 ng/mL; females:
      1.50-38.5 ng/mL). CONCLUSIONS: To the best of the authors' knowledge, the first
      reference interval study for Tg that integrates NACB criteria and TUS assessment
      for the selection of the reference population is provided here.

PMID- 22628334
TI  - Thyroid volume influences serum calcitonin levels in a thyroid-healthy
      population: results of a 3-assay, 519 subjects study.
AB  - BACKGROUND: We aimed to assess determinants for serum calcitonin (CT) levels and
      to define reference ranges for different CT immunoassays integrating thyroid
      ultrasonography (TUS) and conventional clinical and biochemical criteria to
      select the reference population. METHODS: Five hundred and nineteen thyroid
      healthy subjects were included in this prospective cross-sectional population
      study. Thyroid volume was measured by TUS, while serum CT levels were measured by
      three different immunoassays. RESULTS: Significant interassay differences were
      found and the agreement between assays was poor. CT levels were higher in males
      than in females in all immunoassays. Using the first two assays, both gender and
      thyroid volume were independent determinants for CT levels. While using the third
      assay, one thyroid volume was the only determinant for CT levels. CONCLUSIONS:
      Thyroid volume is a relevant determinant for CT levels. In the clinical practice,
      the difference of the thyroid sizes in males and females warrants gender-specific
      reference ranges.

PMID- 22628335
TI  - Impact of the reference values on the clinically-relevant cut-offs. The example
      of cortisol testing in children.
AB  - BACKGROUND: After modification of our routine cortisol assay, we questioned the
      reference ranges for basal and stimulated cortisol plasma concentration in
      children. METHODS: We retrospectively addressed the relevance of using the
      manufacturer's normal reference range for basal cortisol and investigated its
      response to glucagon-betaxolol testing. RESULTS: Basal morning cortisol was 260
      (98-604) nmol/L [manufacturer's normal range (185-624) nmol/L: 26% subjects had
      "low" basal cortisol]. Upon testing cortisol increased to 502 (117-856) nmol/L.
      If a recently described 100% specificity threshold (403 nmol/L) is used it would
      amount to 31% adrenal insufficient children in apparently unaffected children.
      Basal and stimulated cortisol obtained with our prior radioimmunoassay (RIA) in a
      sub-group of subjects were lower: 411 (187-1061) and 770 (329-1542) nmol/L. Using
      the 403 nmol/L threshold with the radioimmunoassay would result in only 5%
      adrenal insufficient children. CONCLUSIONS: This shows again that laboratories
      have to advertise the need to establish reference values for given populations,
      both for basal or stimulated hormone levels. Failure to apply this rule will
      elicit false-positive and more critically, false-negative results.

PMID- 22628336
TI  - The concentration of adiponectin in breast milk is related to maternal hormonal
      and inflammatory status during 6 months of lactation.
AB  - BACKGROUND: Varying concentrations of adiponectin are present in human breast
      milk. This study aimed to determine the relationship between milk adiponectin
      concentration and the hormonal and inflammatory status of breast-feeding women.
      METHODS: Blood and breast milk samples were collected from 157 breast-feeding
      women enrolled at 1-180 post-partum lactation days. The milk and serum
      adiponectin concentrations were measured by radioimmunoassays. The serum
      oestradiol, prolactin, thyroxine, triiodothyronine, cortisol and insulin
      concentrations were measured by the chemiluminescent immunometric method. The
      leptin, resistin and ghrelin concentrations were measured by the immunometric
      methods. RESULTS: The milk, but not serum, adiponectin concentration increased
      during the 180-day lactation period and displayed a positive correlation
      (r=0.748; p<0.001) to the lactation day. The milk adiponectin concentration was
      positively correlated to the maternal serum ghrelin concentration (r=0.299;
      p<0.001) and inversely to the maternal serum oestradiol (r=-0.366; p<0.001),
      prolactin (r=-0.444; p<0.001), thyroxine (r=-0.355; p<0.001), triiodothyronine
      (r=-0.291; p<0.001), cortisol (r=-0.537; p<0.001), and C-reactive protein (r=
      0.483; p<0.001) concentrations. The milk adiponectin concentration was positively
      correlated to the milk leptin (r=0.344; p<0.001) and ghrelin (r=0.458; p<0.001)
      concentrations, and inversely to milk resistin concentration (r=-0.518; p<0.001).
      The serum adiponectin concentration in breastfed infants was positively
      correlated (r=0.711; p<0.001) to the adiponectin concentration in the consumed
      breast milk. CONCLUSIONS: The adiponectin concentration in breast milk increases
      over time during lactation and is affected by the maternal hormonal and
      inflammatory status.

PMID- 22628337
TI  - Reference intervals and biological variation for kallikrein 6: influence of age
      and renal failure.
AB  - BACKGROUND: Kallikrein 6 (KLK6) is a serine protease involved in numerous
      cellular processes, up-regulated in many cancers and associated with some
      neurodegenerative disorders. The aim of this study was to establish a reference
      interval and estimate the biological variation of KLK6 in serum samples of
      adults. Furthermore, levels of this protein in patients with renal failure were
      also studied. METHODS: Serum samples from healthy volunteers (n=136) were
      collected. Between 15 and 18 additional samples from four of these subjects were
      obtained over a period of 2 months. Samples from individuals (n=1043) who visited
      the University Health Network for a routine check-up were collected to study the
      association between KLK6 with age and gender. Samples from patients with renal
      failure (n=106) were also obtained and KLK6 and creatinine concentrations were
      analyzed by ELISA and an automated enzymatic method, respectively. RESULTS: The
      reference interval was established to be 1.04-3.93 ng/mL. The index of
      individuality was 0.43 and the reference change value was 35%. Only two serum
      samples would be required to estimate the homeostatic setting point of an
      individual. There is a weak but highly significant positive correlation between
      KLK6 and age (p<0.0001). Furthermore, there is a significant positive correlation
      between serum concentrations of KLK6 and creatinine (p<0.0001), in patients with
      renal failure. CONCLUSIONS: The established reference interval for KLK6 and the
      estimation of its biological variation will further aid in the clinical use of
      this protein as a serum marker of malignancy and other diseases.

PMID- 22628338
TI  - Reference intervals of extended erythrocyte and reticulocyte parameters.
AB  - BACKGROUND: Optical analysis of erythrocytes can provide information on the
      hemoglobin concentration and content of reticulocytes and mature erythrocytes.
      Such parameters have proven clinical utility in anemia diagnosis and therapy
      monitoring. For interpretation, reliable reference ranges are needed. The aim of
      this study was to establish reference intervals for extended erythrocyte and
      reticulocyte parameters as measured with the Abbott CELL-DYN Sapphire hematology
      analyzer. Secondary aims were to study sample stability and to investigate gender
      and age dependency of the reference ranges. METHODS: Extended RBC parameters
      were measured in routine samples of a primary health care laboratory. The study
      cohort included 8161 samples of unique individuals, which were analyzed using
      Bhattacharya statistics. As a comparison, reference intervals were calculated in
      a subset of individuals without iron depletion. RESULTS: The majority of
      erythrocyte and reticulocyte parameters were normally distributed, allowing
      calculation of reference intervals. Only for hypo- and hyperchromic erythrocytes
      non-parametric statistics had to be used. The reference range for mean cellular
      hemoglobin content of reticulocytes (MCHr) was 28.5-34.5 pg (1.77-2.14 fmol) in
      the entire study group and 26.0-35.1 pg (1.60-2.17 fmol) in the non iron-depleted
      subgroup. No differences between sexes were found. Most parameters showed
      significant age effects in children and adolescents. CONCLUSIONS: Reference
      intervals have been established for extended RBC and reticulocyte parameters for
      the CELL-DYN Sapphire. Gender effects could not be demonstrated and age effects
      were of limited size, except for individuals younger than 18 years. Extended RBC
      parameters are stable for at least 6 h after blood collection.

PMID- 22628339
TI  - Haematological and iron metabolism parameters in professional cyclists during the
      Giro d'Italia 3-weeks stage race.
AB  - BACKGROUND: Haematological assessment is crucial for evaluating athletes healthy
      status. Professional athletes experience physiological modifications during
      competitions and over a season: the risk of sports anaemia is high. Few
      descriptions of haematological parameters behaviour during a 3-weeks cycling
      stage race have been published. METHODS: We studied nine professional cyclists
      engaged in the 2011 Giro d'Italia stage race. Pre-analytical and analytical
      phases tightly followed academic and anti-doping authorities' recommendations.
      Haematological and iron metabolism parameters were measured days -1 (pre-race),
      12 and 22 during the race. RESULTS: Haemoglobin, red blood cells and haematocrit
      decreased during the race with a stabilisation in the second half, but final
      values were lower than baseline. Reticulocytes did not modify, whilst the
      immature reticulocyte fraction increased. No differences were found in red blood
      cells volume and corpuscular haemoglobin content, neither in iron metabolism
      markers. The acute phase proteins, haptoglobin and C-reactive protein, both
      increased over the race, while haemoglobin and haptoglobin were inversely
      related. CONCLUSIONS: These data are important for improving the knowledge of
      physiological modifications in haematological and iron metabolism parameters of
      professional athletes during highly demanding competitions. This is the first
      report, in the ambit of a stage race, in which the pre-analytical phase
      standardisation has been applied.

PMID- 22628340
TI  - Reference change values for lens culinaris agglutinin-reactive alpha-fetoprotein
      and des-gamma-carboxy prothrombin in patients with chronic hepatitis C.
AB  - BACKGROUND: Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) and des
      gamma-carboxy prothrombin (DCP) have been routinely used as serological tumor
      markers of hepatocellular carcinoma (HCC) for surveillance. The aims of this
      study were: (i) to determine the biological variation of AFP-L3 and DCP in
      patients with chronic hepatitis C; and (ii) to calculate the reference change
      values (RCVs) of AFP-L3 and DCP. METHODS: Ten patients with cirrhosis due to
      hepatitis C virus (HCV) infection and without HCC were enrolled in the study.
      Serum samples were collected at 14-day intervals, and 10 samples in total were
      obtained for each patient. AFP-L3 and DCP levels were measured by microchip
      capillary electrophoresis and liquid-phase binding assay. Intra-individual
      (CV(I)) and inter-individual (CV(G)) biological variations and RCVs were
      estimated from the data generated. RESULTS: The CV(I) was 29.0% for AFP-L3 and
      24.6% for DCP, and CV(G) was 63.5% for AFP-L3 and 40.4% for DCP. The RCVs for AFP
      L3 and DCP were 68.3% and 58.5%, respectively. CONCLUSIONS: Increases in values
      for AFP-L3 and DCP within 68.3% and 58.5% may be biological variations. Clinician
      should take these variations into consideration for the management of patients
      with HCV infection under surveillance of HCC.

PMID- 22628342
TI  - Reference values for new red blood cell and platelet parameters on the Abbott
      Diagnostics Cell-Dyn Sapphire.

PMID- 22628350
TI  - Computing posterior probabilities for score-based alignments using ppALIGN.
AB  - Score-based pairwise alignments are widely used in bioinformatics in particular
      with molecular database search tools, such as the BLAST family.  Due to
      sophisticated heuristics, such algorithms are usually fast but  the underlying
      scoring model unfortunately lacks a statistical description of the reliability of
      the reported alignments.  In particular, close to gaps, in low-score or low
      complexity regions, a huge number of alternative alignments arise which results
      in a decrease of the certainty of the alignment. ppALIGN is a software package
      that uses hidden Markov Model techniques to compute position-wise reliability of
      score-based pairwise alignments of DNA or protein sequences.  The design of the
      model allows for a direct connection between the scoring function and the
      parameters of the probabilistic model. For this reason it is suitable to analyze
      the outcomes of popular score based aligners and search tools without having to
      choose a complicated set of parameters. By contrast, our program only requires
      the classical score parameters (the scoring function and gap costs). The package
      comes along with a library written in C++, a standalone program for user defined
      alignments (ppALIGN) and another program (ppBLAST) which can process a complete
      result set of BLAST.  The main algorithms essentially exhibit a linear time
      complexity (in the alignment lengths), and they are hence suitable for on-line
      computations. We have also included alternative decoding algorithms to provide
      alternative alignments. ppALIGN is a fast program/library that helps detect and
      quantify questionable regions in pairwise alignments.  Due to its structure, the
      input/output interface it can to be connected to other post-processing tools. 
      Empirically, we illustrate its usefulness in terms of correctly predicted
      reliable regions for sequences generated using the ROSE model for sequence
      evolution, and identify sensor-specific regions in the denitrifying
      betaproteobacterium Aromatoleum aromaticum.

PMID- 22628351
TI  - QTL mapping using a memetic algorithm with modifications of BIC as fitness
      function.
AB  - The problem of locating quantitative trait loci (QTL) for experimental
      populations can be approached by multiple regression analysis. In this context
      variable selection  using a modification of the Bayesian Information Criterion
      (mBIC)  has been well established  in the past. In this article a memetic
      algorithm (MA) is introduced to find the model which minimizes the selection
      criterion. Apart from mBIC also a second modification (mBIC2) is considered,
      which has the property of controlling the false discovery rate.  Given the
      Bayesian nature of our selection criteria, we are not only interested in finding
      the best model, but also in computing marker posterior probabilities using all
      models visited by MA. In a simulation study MA (with mBIC and mBIC2) is compared
      with a parallel genetic algorithm (PGA) which has been previously suggested for
      QTL mapping. It turns out that MA  in combination with mBIC2 performs best, where
      determining QTL positions based on marker posterior probabilities yields even
      better results than using the best model selected by MA. Finally we consider a
      real data set from the literature and show that MA can also be extended to
      multiple interval mapping, which potentially increases the precision with which
      the exact location of QTLs can be estimated.

PMID- 22628352
TI  - Building bridges: an interpretive phenomenological analysis of nurse educators'
      clinical experience using the T.R.U.S.T. Model for inclusive spiritual care.
AB  - Educating nurses to provide evidence-based, non-intrusive spiritual care in
      today's pluralistic context is both daunting and essential. Qualitative research
      is needed to investigate what helps nurse educators feel more prepared to meet
      this challenge. This paper presents findings from an interpretive
      phenomenological analysis of the experience of nurse educators who used the 
      T.R.U.S.T. Model for Inclusive Spiritual Care  in their clinical teaching. The
      T.R.U.S.T. Model is an evidence-based, non-linear resource developed by the
      author and piloted in the undergraduate nursing program in which she teaches.
      Three themes are presented:  "The T.R.U.S.T. Model as a bridge to spiritual
      exploration"; "blockades to the bridge"; and "unblocking the bridge".  T.R.U.S.T.
      was found to have a positive influence on nurse educators' comfort and confidence
      in the teaching of spiritual care. Recommendations for maximizing the model's
      positive impact are provided, along with "embodied" resources to support holistic
      teaching and learning about spiritual care.

PMID- 22628353
TI  - International experiences in nursing education: a review of the literature.
AB  - Service learning and study abroad opportunities have become increasingly popular
      in nursing education in the past decade.  The purpose of this systematic review
      was to explore existing literature concerning global health experiences in
      nursing education.  Twenty-three empirical articles from 2003 to 2010 were
      reviewed, building upon existing reviews of international nursing education
      literature.  Research on two-way exchange experiences and models for best
      practice were found to be lacking.  While an array of countries were represented
      as the visiting or hosting side of the experience, few co-authors from host
      countries were found, particularly in literature originating from the U.S.  The
      authors recommend that two-way exchange programs be evaluated to identify
      successful strategies and barriers to success.  Ongoing evaluation of exchanges
      is necessary to ensure continued sustainable partnership and exchange in
      immersion experiences for nursing students.

PMID- 22628356
TI  - Targeted minimum loss based estimator that outperforms a given estimator.
AB  - Targeted minimum loss based estimation (TMLE) provides a template for the
      construction of semiparametric locally efficient double robust substitution
      estimators of the target parameter of the data generating distribution in  a
      semiparametric censored data or causal inference model (van der Laan and Rubin
      (2006), van der Laan (2008), van der Laan and Rose (2011)). In this article we
      demonstrate how to construct a  TMLE that also satisfies the property that it is
      at least as efficient as a user supplied asymptotically linear estimator. In
      particular it is shown that  this type of TMLE can incorporate empirical
      efficiency maximization as in  Rubin and van der Laan (2008),  Tan (2008, 2010),
      Rotnitzky et al. (2012), and retain double robustness. For the sake of
      illustration we focus on estimation of the additive average causal effect of a
      point treatment on an outcome, adjusting for baseline covariates.

PMID- 22628357
TI  - The large sample bounds on the principal strata effect with application to a
      prostate cancer prevention trial.
AB  - Issues of post-randomization selection bias and truncation-by-death can arise in
      randomized clinical trials; for example, in a cancer prevention trial, an outcome
      such as cancer severity is undefined for individuals who do not develop cancer.
      Restricting analysis to a subpopulation selected after randomization can give
      rise to biased outcome comparisons. One approach to deal with such issues is to
      consider the principal strata effect (PSE, or equally, the survivor average
      causal effect). PSE is defined as the effect of treatment on the outcome among
      the subpopulation that would have been selected under either treatment arm.
      Unfortunately, the PSE cannot generally be estimated without the identifying
      assumptions; however, the bounds can be derived using a deterministic causal
      model. In this paper, we propose a number of assumptions for deriving the bounds
      with narrow width. The assumptions and bounds, which differ from those introduced
      by Zhang and Rubin (2003), are illustrated using data from a randomized prostate
      cancer prevention trial.

PMID- 22628358
TI  - Smoothness selection for penalized quantile regression splines.
AB  - Modern data-rich analyses may call for fitting a large number of nonparametric
      quantile regressions.  For example, growth charts may be constructed for each of
      a collection of variables, to identify those for which individuals with a
      disorder tend to fall in the tails of their age-specific distribution; such
      variables might serve as developmental biomarkers.  When such a large set of
      analyses are carried out by penalized spline smoothing, reliable automatic
      selection of the smoothing parameter is particularly important.  We show that two
      popular methods for smoothness selection may tend to overfit when estimating
      extreme quantiles as a smooth function of a predictor such as age; and that
      improved results can be obtained by multifold cross-validation or by a novel
      likelihood approach.  A simulation study, and an application to a functional
      magnetic resonance imaging data set, demonstrate the favorable performance of our
      methods.

PMID- 22628359
TI  - Evaluation of a novel collagen-gelatin scaffold for achieving the sustained
      release of basic fibroblast growth factor in a diabetic mouse model.
AB  - The objective of this study was to evaluate the ability of a scaffold, collagen
      gelatin sponge (CGS), to release basic fibroblast growth factor (bFGF) in a
      sustained manner, using a pressure-induced decubitus ulcer model involving
      genetically diabetic mice. We confirmed that CGSs impregnated with a bFGF
      concentration of up to 50 ug/cm(2) were able to sustain the release of bFGF
      throughout their biodegradation. We prepared decubitus ulcers on diabetic mice.
      After debriding the ulcers, we implanted CGSs (diameter 8 mm) impregnated with
      normal saline solution (NSS) or bFGF solution (7, 14, 28 or 50 ug/cm(2)). At 1
      and 2 weeks after implantation, the mice were sacrificed and tissue specimens
      were obtained. The wound area, neoepithelium length and numbers and total area of
      newly formed capillaries were evaluated. The CGSs impregnated with NSS became
      infected and degraded, whereas the CGSs impregnated with 7 or 14 ug/cm(2) bFGF
      displayed accelerated dermis-like tissue formation and the CGSs impregnated with
      14 ug/cm(2) bFGF produced significant improvements in the remaining wound area,
      neoepithelium length and numbers and total area of newly formed capillaries
      compared with the NSS group. No significant difference was observed between the
      NSS and 50 ug/cm(2) bFGF groups. CGSs impregnated with 7-14 ug/cm(2) bFGF
      accelerated wound healing, and an excess amount of bFGF did not increase the
      wound-healing efficacy of the CGSs. Our CGS is a scaffold that can release
      positively charged growth factors such as bFGF in a sustained manner and shows
      promise as a scaffold for skin regeneration.

PMID- 22628360
TI  - PTEN hamartoma tumor syndrome and Gorham-Stout phenomenon.
AB  - PTEN: hamartoma tumor syndrome (PHTS) is a group of syndromes caused by mutations
      in PTEN. Gorham-Stout phenomenon (GSP) is a rare condition characterized by
      proliferation of vascular structures in bones, resulting in progressive
      osteolysis. Here we present a 1-year-old boy with PHTS and GSP. The lesion that
      later proved to be GSP was evident from the age of 4 months, and became
      symptomatic at the age of 1 year. Eventually, he developed a fatal chylothorax.
      Mutation analysis revealed a germline heterozygous mutation c.517 C>T
      (p.Arg173Cys) in exon 6 of PTEN. Analysis of the lymphatic malformation (LM)
      tissue revealed no loss of heterozygosity (LOH) nor a second, somatic PTEN
      mutation of the remaining wild type allele. The germline p.Arg173Cys mutation was
      also present in the mother and the propositus' younger sister and brother.
      Further molecular work-up showed a heterozygous variant c.2180C>T (p.Ala727Val)
      FLT4 in the LM tissue, which was also present in the germline of mother and two
      siblings. GSP has not been reported before in a patient with a PTEN mutation. Up
      to this date, this mutation is the only genetic defect possibly involved in the
      etiology of GSP which is plausible given the known function of PTEN in angiogenic
      signaling.

PMID- 22628361
TI  - Crystal structure of a template-assembled synthetic G-quadruplex.

PMID- 22628362
TI  - Enhanced endothelial differentiation of adipose-derived stem cells by substrate
      nanotopography.
AB  - Adipose-derived stem cells (ADSCs) have great potential as a cell source for
      tissue engineering and regenerative medicine because they are easier to obtain,
      have lower donor-site morbidity and are available in larger numbers than stem
      cells harvested using bone marrow aspiration. Until now, little has been known
      about how nanotopography affects the proliferation and endothelial
      differentiation of ADSCs. In the present study, two nanograting substrates with a
      period (ridge and groove) of about 250 and 500 nm, respectively, were fabricated
      on quartz and their effect on ADSC fate was investigated. The results showed that
      proliferation of ADSCs on nanograting substrates decreased while cell attachment
      was not significantly affected compared to a flat substrate. Endothelial
      differentiation of ADSCs on both flat and nanograting substrates can be induced
      with vascular endothelial growth factor, as shown by immunofluorescent staining.
      Quantitative real-time PCR analysis showed significantly enhanced upregulation of
      vWF, PECAM-1 and VE-cadherin at the gene level by ADSCs on the nanograting
      substrates. In vitro angiogenesis assay on Matrigel showed that nanograting
      substrates enhanced capillary tube formation. This study highlights the
      beneficial influence of nanotopography on the differentiation of ADSC into
      endothelial cells which play an important role in vascularization.

PMID- 22628363
TI  - Sirenomelia and cyclopia in the same patient after a cluster of cyclopia and
      sirenomelia in Cali (South America).

PMID- 22628364
TI  - Seed colour loci, homoeology and linkage groups of the C genome chromosomes
      revealed in Brassica rapa-B. oleracea monosomic alien addition lines.
AB  - BACKGROUND AND AIMS: Brassica rapa and B. oleracea are the progenitors of oilseed
      rape B. napus. The addition of each chromosome of B. oleracea to the chromosome
      complement of B. rapa results in a series of monosomic alien addition lines
      (MAALs). Analysis of MAALs determines which B. oleracea chromosomes carry genes
      controlling specific phenotypic traits, such as seed colour. Yellow-seeded
      oilseed rape is a desirable breeding goal both for food and livestock feed end
      uses that relate to oil, protein and fibre contents. The aims of this study
      included developing a missing MAAL to complement an available series, for studies
      on seed colour control, chromosome homoeology and assignment of linkage groups to
      B. oleracea chromosomes. METHODS: A new batch of B. rapa-B. oleracea aneuploids
      was produced to generate the missing MAAL. Seed colour and other plant
      morphological features relevant to differentiation of MAALs were recorded. For
      chromosome characterization, Snow's carmine, fluorescence in situ hybridization
      (FISH) and genomic in situ hybridization (GISH) were used. KEY RESULTS: The final
      MAAL was developed. Morphological traits that differentiated the MAALs comprised
      cotyledon number, leaf morphology, flower colour and seed colour. Seed colour was
      controlled by major genes on two B. oleracea chromosomes and minor genes on five
      other chromosomes of this species. Homoeologous pairing was largely between
      chromosomes with similar centromeric positions. FISH, GISH and a parallel
      microsatellite marker analysis defined the chromosomes in terms of their linkage
      groups. Conclusions A complete set of MAALs is now available for genetic,
      genomic, evolutionary and breeding perspectives. Defining chromosomes that carry
      specific genes, physical localization of DNA markers and access to established
      genetic linkage maps contribute to the integration of these approaches,
      manifested in the confirmed correspondence of linkage groups with specific
      chromosomes. Applications include marker-assisted selection and breeding for
      yellow seeds.

PMID- 22628365
TI  - A molecular phylogeny and classification of Leptochloa (Poaceae: Chloridoideae:
      Chlorideae) sensu lato and related genera.
AB  - BACKGROUND AND AIMS: Leptochloa (including Diplachne) sensu lato (s.l.) comprises
      a diverse assemblage of C(4) (NAD-ME and PCK) grasses with approx. 32 annual or
      perennial species. Evolutionary relationships and a modern classification of
      Leptochloa spp. based on the study of molecular characters have only been
      superficially investigated in four species. The goals of this study were to
      reconstruct the evolutionary history of Leptochloa s.l. with molecular data and
      broad taxon sampling. METHODS: A phylogenetic analysis was conducted of 130
      species (mostly Chloridoideae), of which 22 are placed in Leptochloa, using five
      plastid (rpL32-trn-L, ndhA intron, rps16 intron, rps16-trnK and ccsA) and the
      nuclear ITS 1 and 2 (ribosomal internal transcribed spacer regions) to infer
      evolutionary relationships and revise the classification. KEY RESULTS: Leptochloa
      s.l. is polyphyletic and strong support was found for five lineages. Embedded
      within the Leptochloa sensu stricto (s.s.) clade are two Trichloris spp. and
      embedded in Dinebra are Drake-brockmania and 19 Leptochloa spp. CONCLUSIONS: The
      molecular results support the dissolution of Leptochloa s.l. into the following
      five genera: Dinebra with 23 species, Diplachne with two species, Disakisperma
      with three species, Leptochloa s.s. with five species and a new genus,
      Trigonochloa, with two species.

PMID- 22628366
TI  - Signal honesty and cost of pollinator rewards in Dalechampia scandens
      (Euphorbiaceae).
AB  - BACKGROUND AND AIMS: Most species of Dalechampia vines (Euphorbiaceae) attract
      bee pollinators with terpenoid resins secreted by a gland-like structure in the
      inflorescence. In some species, pollinating bees appear to preferentially visit
      inflorescences (blossoms) with large resin-producing glands, whereas in other
      species bees preferentially visit blossoms with large involucral bracts. In this
      study, the reliability of bract and gland size as signals of the quantity of
      resin produced in one species, D. scandens, was assessed. Whether resin secretion
      has a cost with respect to the number or mass of the seeds produced by a blossom
      was also examined. METHODS: Measurements were made of bract size, gland size and
      the amount of resin secreted by blossoms of D. scandens maintained in a common
      environment, and the relationships between these traits were analysed. Resin
      production was also manipulated, and the effects of the manipulation were tested
      on seed set and seed mass. KEY RESULTS: The amount of resin produced was better
      predicted by the size of the gland than by the size of the bract. Furthermore,
      when the effect of gland size was accounted for, bract size only weakly predicted
      the amount of resin produced. Neither an increase in resin secretion (by daily
      removal of the resin) nor a decrease (by removal of the resin gland) affected
      seed set or seed mass detectably, but resin production correlated positively with
      mean seed mass at the individual level once the size of the resin gland was
      accounted for. CONCLUSIONS: Gland size is a better indicator of the amount of
      reward than bract size, although the latter remained an honest signal of the
      quantity of resin produced. Resin secretion has no detectable cost in terms of
      seed production, but may be condition dependent, as suggested by a positive
      correlation with seed mass at the individual level.

PMID- 22628367
TI  - Perspectives from the common ground.

PMID- 22628368
TI  - Determinants of quality of life in HIV-infected patients receiving highly active
      antiretroviral treatment at a medical college ART center in Kolkata, India.
AB  - Health-related quality of life (QOL) has become a high priority of long-term
      management of HIV-infected individuals. The newly diagnosed HIV cases were
      assessed to obtain sociodemographic and clinical findings. Eyesenk Personality
      Questionnaire (EPQ), World Health Organization Quality of Life Brief (WHOQOL
      BREF) for HIV-infected patients, and Beck Depression Inventory (BDI) were used to
      get data regarding personality traits, QOL, and depression scores. A total of 175
      patients were included in the study, 128 (73.1%) men and 47 (26.9%) women.
      Overall 56% of patients screened positive for depression. Presence of depression
      and high neuroticism score in the personality profile of HIV-infected patients
      are significantly associated with poorer QOL. High neuroticism score was a strong
      predictor of poorer QOL in psychological and spiritual domain. Management of HIV
      infected patients therefore needs to address these psychological issues. 

PMID- 22628370
TI  - Increased adolescent HIV infection during pregnancy leads to increase in
      perinatal transmission at urban referral center.
AB  - BACKGROUND: Undiagnosed HIV during pregnancy leads to increased perinatal
      infection. Four cases of adolescents/young adults with HIV contracted during
      pregnancy, after initial negative HIV testing, led to 4 cases of perinatal HIV,
      which were diagnosed only after AIDS-defining illness occurred in infants. These
      cases were missed despite HIV testing during pregnancy. This identifies a change
      in pattern for perinatal infection: increased adolescent/young adult HIV leading
      to increased perinatal risk. METHODS: A 10-year retrospective chart review on HIV
      positive infants in an urban referral center. Charts were reviewed for timing of
      maternal HIV testing and reason for infant HIV diagnosis. RESULTS: Twenty
      infected infants were referred over a 10-year period. Four HIV-infected infants
      were identified within a 2-year time frame at the end of the 10-year period. The
      4 mothers were HIV negative, based on early peripartum testing (3 in first
      trimester and 1 in second trimester) and became infected or seroconverted during
      pregnancy after initial HIV test. The mothers diagnosed were all under the age of
      25. CONCLUSIONS: Rapid HIV testing at the time of delivery, despite a negative
      HIV result in early pregnancy, will prevent the delay in HIV diagnosis in both
      the mother and the infant and thus decrease HIV transmission from mother to
      child.

PMID- 22628369
TI  - Enhancing HIV medication adherence in India.
AB  - BACKGROUND: This pilot study evaluated an intervention designed to enhance
      adherence among those new to antiretroviral therapy. METHODS: Participants (n =
      80) were recruited from a hospital clinic in Chandigarh, India, and randomized to
      a 3-month group intervention or individual enhanced standard of care followed by
      crossover of condition and assessed over 6 months. Adherence was measured by
      prescription refill, pill count, and self-report. RESULTS: At baseline, 56% of
      group condition (immediate intervention) and 54% of individual condition (delayed
      intervention) participants were nonadherent by pill count and 23% of group and
      26% of individual condition participants self-reported skipping medication at
      least once over the last 3 months. From the postintervention to long-term follow
      up, adherence in the group condition (immediate intervention) improved in
      comparison with adherence in the individual condition (delayed intervention;
      chi(2) = 5.67, P = .02). CONCLUSIONS: Results support the use of interventions
      early in treatment to provide information and social support to establish long
      term healthy adherence behaviors.

PMID- 22628371
TI  - Low muscle glycogen concentration does not suppress the anabolic response to
      resistance exercise.
AB  - We determined the effect of muscle glycogen concentration and postexercise
      nutrition on anabolic signaling and rates of myofibrillar protein synthesis after
      resistance exercise (REX). Sixteen young, healthy men matched for age, body mass,
      peak oxygen uptake (Vo(2peak)) and strength (one repetition maximum; 1RM) were
      randomly assigned to either a nutrient or placebo group. After 48 h diet and
      exercise control, subjects undertook a glycogen-depletion protocol consisting of
      one-leg cycling to fatigue (LOW), whereas the other leg rested (NORM). The next
      morning following an overnight fast, a primed, constant infusion of l-[ring
      (13)C(6)] phenylalanine was commenced and subjects completed 8 sets of 5
      unilateral leg press repetitions at 80% 1RM. Immediately after REX and 2 h later,
      subjects consumed a 500 ml bolus of a protein/CHO (20 g whey + 40 g maltodextrin)
      or placebo beverage. Muscle biopsies from the vastus lateralis of both legs were
      taken at rest and 1 and 4 h after REX. Muscle glycogen concentration was higher
      in the NORM than LOW at all time points in both nutrient and placebo groups (P <
      0.05). Postexercise Akt-p70S6K-rpS6 phosphorylation increased in both groups with
      no differences between legs (P < 0.05). mTOR(Ser2448) phosphorylation in placebo
      increased 1 h after exercise in NORM (P < 0.05), whereas mTOR increased ~4-fold
      in LOW (P < 0.01) and ~11 fold in NORM with nutrient (P < 0.01; different between
      legs P < 0.05). Post-exercise rates of MPS were not different between NORM and
      LOW in nutrient (0.070 +/- 0.022 vs. 0.068 +/- 0.018 %/h) or placebo (0.045 +/-
      0.021 vs. 0.049 +/- 0.017 %/h). We conclude that commencing high-intensity REX
      with low muscle glycogen availability does not compromise the anabolic signal and
      subsequent rates of MPS, at least during the early (4 h) postexercise recovery
      period.

PMID- 22628372
TI  - Upper airway collapsibility and patterns of flow limitation at constant end
      expiratory lung volume.
AB  - The passive pharyngeal critical closing pressure (Pcrit) is measured using a
      series of pressure drops. However, pressure drops also lower end-expiratory lung
      volume (EELV), which independently affects Pcrit. We describe a technique to
      measure Pcrit at a constant EELV. Continuous positive airway pressure (CPAP)
      treated obstructive sleep apnea (OSA) patients and controls were instrumented
      with an epiglottic catheter, magnetometers (to measure change in EELV), and nasal
      mask/pneumotachograph and slept supine on nasal CPAP. Pcrit was measured in
      standard fashion and using our novel "biphasic technique" in which expiratory
      pressure only was lowered for 1 min before the inspiratory pressure was dropped;
      this allowed EELV to decrease to the drop level before performing the pressure
      drop. Seven OSA and three controls were studied. The biphasic technique
      successfully lowered EELV before the inspiratory pressure drop. Pcrit was similar
      between the standard and biphasic techniques (-0.4 +/- 2.6 vs. -0.6 +/- 2.3
      cmH(2)O, respectively, P = 0.84). Interestingly, we noted three different
      patterns of flow limitation: 1) classic Starling resistor type: flow fixed and
      independent of downstream pressure; 2) negative effort dependence within breaths:
      substantial decrease in flow, sometimes with complete collapse, as downstream
      pressure decreased; and 3) and negative effort dependence across breaths:
      progressive reductions in peak flow as respiratory effort on successive breaths
      increased. Overall, EELV changes do not influence standard passive Pcrit
      measurements if breaths 3-5 of pressure drops are used. These results also
      highlight the importance of inspiratory collapse in OSA pathogenesis. The cause
      of negative effort dependence within and across breaths is not known and requires
      further study.

PMID- 22628373
TI  - Low-intensity exercise can increase muscle mass and strength proportionally to
      enhanced metabolic stress under ischemic conditions.
AB  - Skeletal muscle bulk and strength are becoming important therapeutic targets in
      medicine. To increase muscle mass, however, intensive, long-term mechanical
      stress must be applied to the muscles, and such stress is often accompanied by
      orthopedic and cardiovascular problems. We examined the effects of circulatory
      occlusion in resistance training combined with a very low-intensity mechanical
      load on enhancing muscular metabolic stress and thereby increasing muscle bulk.
      Muscular metabolic stress, as indicated by the increases in inorganic phosphate
      (P(i)) and a decrease in intramuscular pH, was evaluated by (31)P-magnetic
      resonance spectroscopy during unilateral plantar-flexion at 20% of the one
      repetition maximum (1-RM) with circulatory occlusion for 2 min in 14 healthy,
      male untrained participants (22 yr) at baseline. Participants performed two sets
      of the same exercise with a 30-s rest between sets, 2 times/day, 3 days/wk, for 4
      wk. The muscle cross-sectional area (MCA) of the plantar-flexors and the 1-RM
      were measured at baseline and after 2 and 4 wk of training. MCA and 1-RM were
      significantly increased after 2 and 4 wk (P < 0.05, respectively). The increase
      in MCA at 2 wk was significantly (P < 0.05) correlated with the changes in P(i)
      (r = 0.876) and intramuscular pH (r = 0.601). Furthermore, the increases in MCA
      at 4 wk and 1-RM at 2 wk were also correlated with the metabolic stress. Thus
      enhanced metabolic stress in exercising muscle is a key mechanism for favorable
      effects by resistance training. Low-intensity resistance exercise provides
      successful outcomes when performed with circulatory occlusion, even with a short
      training period.

PMID- 22628374
TI  - Role of glutathione in lung retention of 99mTc-hexamethylpropyleneamine oxime in
      two unique rat models of hyperoxic lung injury.
AB  - Rat exposure to 60% oxygen (O(2)) for 7 days (hyper-60) or to >95% O(2) for 2
      days followed by 24 h in room air (hyper-95R) confers susceptibility or
      tolerance, respectively, of the otherwise lethal effects of subsequent exposure
      to 100% O(2). The objective of this study was to determine if lung retention of
      the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime
      (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue
      retention of HMPAO is dependent on intracellular content of the antioxidant GSH
      and mitochondrial function. HMPAO was injected intravenously in anesthetized
      rats, and planar images were acquired. We investigated the role of GSH in the
      lung retention of HMPAO by pretreating rats with the GSH-depleting agent diethyl
      maleate (DEM) prior to imaging. We also measured GSH content and activities of
      mitochondrial complexes I and IV in lung homogenate. The lung retention of HMPAO
      increased by ~ 50% and ~ 250% in hyper-60 and hyper-95R rats, respectively,
      compared with retention in rats exposed to room air (normoxic). DEM decreased
      retention in normoxic (~ 26%) and hyper-95R (~ 56%) rats compared with retention
      in the absence of DEM. GSH content increased by 19% and 40% in hyper-60 and hyper
      95R lung homogenate compared with normoxic lung homogenate. Complex I activity
      decreased by ~ 50% in hyper-60 and hyper-95R lung homogenate compared with
      activity in normoxic lung homogenate. However, complex IV activity was increased
      by 32% in hyper-95R lung homogenate only. Furthermore, we identified correlations
      between the GSH content in lung homogenate and the DEM-sensitive fraction of
      HMPAO retention and between the complex IV/complex I activity ratio and the DEM
      insensitive fraction of HMPAO retention. These results suggest that an increase
      in the GSH-dependent component of the lung retention of HMPAO may be a marker of
      tolerance to sustained exposure to hyperoxia.

PMID- 22628375
TI  - Role of Nox isoforms in angiotensin II-induced oxidative stress and endothelial
      dysfunction in brain.
AB  - Angiotensin II (Ang II) promotes vascular disease through several mechanisms
      including by producing oxidative stress and endothelial dysfunction. Although
      multiple potential sources of reactive oxygen species exist, the relative
      importance of each is unclear, particularly in individual vascular beds. In these
      experiments, we examined the role of NADPH oxidase (Nox1 and Nox2) in Ang II
      induced endothelial dysfunction in the cerebral circulation. Treatment with Ang
      II (1.4 mg.kg(-1).day(-1) for 7 days), but not vehicle, increased blood pressure
      in all groups. In wild-type (WT; C57Bl/6) mice, Ang II reduced dilation of the
      basilar artery to the endothelium-dependent agonist acetylcholine compared with
      vehicle but had no effect on responses in Nox2-deficient (Nox2(-/y)) mice. Ang II
      impaired responses to acetylcholine in Nox1 WT (Nox1(+/y)) and caused a small
      reduction in responses to acetylcholine in Nox1-deficient (Nox1(-/y)) mice. Ang
      II did not impair responses to the endothelium-independent agonists nitroprusside
      or papaverine in either group. In WT mice, Ang II increased basal and phorbol
      dibutyrate-stimulated superoxide production in the cerebrovasculature, and these
      increases were abolished in Nox2(-/y) mice. Overall, these data suggest that Nox2
      plays a relatively prominent role in mediating Ang II-induced oxidative stress
      and cerebral endothelial dysfunction, with a minor role for Nox1.

PMID- 22628377
TI  - Glutathione enhances endothelium-mediated control of coronary vascular resistance
      via a ROS- and NO intermediate-dependent mechanism.
AB  - The purpose of this investigation was to determine the effects of acute
      physiological GSH administration on endothelium-mediated reduction in coronary
      vascular resistance (CVR) using isolated perfused Sprague-Dawley rat hearts. A
      dose-response curve to GSH was conducted to determine a threshold concentration
      of GSH. We demonstrate that 30 MUM GSH was sufficient to reduce CVR, and maximal
      dilation was achieved with 1 mM. In subsequent experiments, GSH was administered
      at concentrations of 0 [control (CON)], 1 MUM, or 10 MUM (GSH(10)), and dose
      response curves to the endothelial agonist bradykinin (BK) were constructed.
      These GSH concentrations were chosen because of the physiological relevance and
      because the effects of GSH on BK action could be assessed independent of baseline
      differences in CVR. Sensitivity to BK (EC(50)) was enhanced in GSH(10) vs. CON (P
      < 0.05). This enhancement remained in the presence of nitric oxide (NO) synthase
      inhibition l-(omega)nitro-l-arginine (lNAME) and/or soluble guanylate cyclase
      (sGC) inhibition. Treatment with 4-hydroxy (2,2,6,6-tetramethylpiperidin-1
      yl)oxyl (TEMPOL) enhanced the sensitivity to BK in CON, similar to the effects of
      GSH(10) and GSH(10) + TEMPOL. However, the GSH(10)-dependent enhancement of
      EC(50) observed in the presence of lNAME did not occur in the presence of lNAME +
      TEMPOL or in the presence of lNAME + sGC inhibition and NO scavenging.
      Collectively, these results suggest that GSH enhances BK-mediated dilation and
      reduction in CVR through an antioxidant-dependent mechanism that involves a NO
      intermediate but is unrelated to acute production of NO and GC-dependent effects
      of NO. These results suggest a mechanism whereby physiologically relevant levels
      of GSH modulate the endogenous reactive oxygen species and NO control of
      endothelium-dependent coronary vascular function.

PMID- 22628376
TI  - Reverse right ventricular structural and extracellular matrix remodeling by
      estrogen in severe pulmonary hypertension.
AB  - Chronic pulmonary hypertension (PH) leads to right-ventricular failure (RVF)
      characterized by RV remodeling. Ventricular remodeling is emerging as an
      important process during heart failure and recovery. Remodeling in RVF induced by
      PH is not fully understood. Recently we discovered that estrogen (E2) therapy can
      rescue severe preexisting PH. Here, we focused on whether E2 (42.5 MUg.kg(
      1).day(-1), 10 days) can reverse adverse RV structural and extracellular matrix
      (ECM) remodeling induced by PH using monocrotaline (MCT, 60 mg/kg). RV fibrosis
      was evident in RVF males. Intact females developed less severe RV remodeling
      compared with males and ovariectomized (OVX) females. Novel ECM-degrading
      disintegrin-metalloproteinases ADAM15 and ADAM17 transcripts were elevated ~2
      fold in all RVF animals. E2 therapy reversed RV remodeling in all groups. In
      vitro, E2 directly inhibited ANG II-induced expression of fibrosis markers as
      well as the metalloproteinases in cultured cardiac fibroblasts. Estrogen receptor
      beta agonist diarylpropionitrile (DPN) but not estrogen receptor-alpha agonist
      4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) was as effective as
      E2 in inhibiting expression of these genes. Expression of ECM-interacting cardiac
      fetal-gene osteopontin (OPN) also increased ~9-fold in RVF males. Intact females
      were partially protected from OPN upregulation (~2-fold) but OVX females were
      not. E2 reversed OPN upregulation in all groups. Upregulation of OPN was also
      reversed in vitro by E2. Plasma OPN was elevated in RVF (~1.5-fold) and decreased
      to control levels in the E2 group. RVF resulted in elevated Akt phosphorylation,
      but not ERK, in the RV, and E2 therapy restored Akt phosphorylation. In
      conclusion, E2 therapy reverses adverse RV remodeling associated with PH by
      reversing fibrosis and upregulation of novel ECM enzymes ADAM15, ADAM17, and OPN.
      These effects are likely mediated through estrogen receptor-beta.

PMID- 22628378
TI  - Renovascular reactivity measured by near-infrared spectroscopy.
AB  - Hypotension and shock are risk factors for death, renal insufficiency, and stroke
      in preterm neonates. Goal-directed neonatal hemodynamic management lacks end
      organ monitoring strategies to assess the adequacy of perfusion. Our aim is to
      develop a clinically viable, continuous metric of renovascular reactivity to
      gauge renal perfusion during shock. We present the renovascular reactivity index
      (RVx), which quantifies passivity of renal blood volume to spontaneous changes in
      arterial blood pressure. We tested the ability of the RVx to detect reductions in
      renal blood flow. Hemorrhagic shock was induced in 10 piglets. The RVx was
      monitored as a correlation between slow waves of arterial blood pressure and
      relative total hemoglobin (rTHb) obtained with reflectance near-infrared
      spectroscopy (NIRS) over the kidney. The RVx was compared with laser-Doppler
      measurements of red blood cell flux, and renal laser-Doppler measurements were
      compared with cerebral laser-Doppler measurements. Renal blood flow decreased to
      75%, 50%, and 25% of baseline at perfusion pressures of 60, 45, and 40 mmHg,
      respectively, whereas in the brain these decrements occurred at pressures of 30,
      25, and 15 mmHg, respectively. The RVx compared favorably to the renal laser
      Doppler data. Areas under the receiver operator characteristic curves using renal
      blood flow thresholds of 50% and 25% of baseline were 0.85 (95% CI, 0.83-0.87)
      and 0.90 (95% CI, 0.88-0.92). Renovascular autoregulation can be monitored and is
      impaired in advance of cerebrovascular autoregulation during hemorrhagic shock.

PMID- 22628379
TI  - Locally measured shear moduli of pulmonary tissue and global lung mechanics in
      mechanically ventilated rats.
AB  - This study was aimed at measuring shear moduli in vivo in mechanically ventilated
      rats and comparing them to global lung mechanics. Wistar rats (n = 28) were
      anesthetized, tracheally intubated, and mechanically ventilated in supine
      position. The animals were randomly assigned to the healthy control or the lung
      injury group where lung injury was induced by bronchoalveolar lavage. The
      respiratory system elastance E(rs) was analyzed based on the single compartment
      resistance/elastance lung model using multiple linear regression analysis. The
      shear modulus (G) of alveolar parenchyma was studied using a newly developed
      endoscopic system with adjustable pressure at the tip that was designed to induce
      local mechanostimulation. The data analysis was then carried out with an inverse
      finite element method. G was determined at continuous positive airway pressure
      (CPAP) levels of 15, 17, 20, and 30 mbar. The resulting shear moduli of lungs in
      healthy animals increased from 3.3 +/- 1.4 kPa at 15 mbar CPAP to 5.8 +/- 2.4 kPa
      at 30 mbar CPAP (P = 0.012), whereas G was ~2.5 kPa at all CPAP levels for the
      lung-injured animals. Regression analysis showed a negative correlation between G
      and relative E(rs) in the control group (r = -0.73, P = 0.008 at CPAP = 20 mbar)
      and no significant correlation in the lung injury group. These results suggest
      that the locally measured G were inversely associated with the elastance of the
      respiratory system. Rejecting the study hypothesis the researchers concluded that
      low global respiratory system elastance is related to high local resistance
      against tissue deformation.

PMID- 22628380
TI  - Ecological effects of cell-level processes: genome size, functional traits and
      regional abundance of herbaceous plant species.
AB  - BACKGROUND AND AIMS: Genome size is known to be correlated with a number of
      phenotypic traits associated with cell sizes and cell-division rates. Genome size
      was therefore used as a proxy for them in order to assess how common plant traits
      such as height, specific leaf area and seed size/number predict species regional
      abundance. In this study it is hypothesized that if there is residual correlation
      between genome size and abundance after these traits are partialled out, there
      must be additional ecological effects of cell size and/or cell-division rate.
      METHODS: Variation in genome size, plant traits and regional abundance were
      examined in 436 herbaceous species of central European flora, and relationships
      were sought for among these variables by correlation and path analysis. KEY
      RESULTS: Species regional abundance was weakly but significantly correlated with
      genome size; the relationship was stronger for annuals (R(2) = 0.145) than for
      perennials (R(2) = 0.027). In annuals, genome size was linked to abundance via
      its effect on seed size, which constrains seed number and hence population growth
      rate. In perennials, it weakly affected (via height and specific leaf area)
      competitive ability. These relationships did not change qualitatively after
      phylogenetic correction. In both annuals and perennials there was an unresolved
      effect of genome size on abundance. CONCLUSIONS: The findings indicate that
      additional predictors of regional abundance should be sought among variables that
      are linked to cell size and cell-division rate. Signals of these cell-level
      processes remain identifiable even at the landscape scale, and show deep
      differences between perennials and annuals. Plant population biology could thus
      possibly benefit from more systematic use of indicators of cell-level processes.

PMID- 22628382
TI  - Perceptions of domestic violence: the effects of domestic violence myths,
      victim's relationship with her abuser, and the decision to return to her abuser.
AB  - Researchers in this study examined the attitudes toward domestic violence, the
      victim, and her perpetrator. A total of 194 participants were randomly assigned
      to one of 4 hypothetical scenarios to evaluate how observers' perceptions were
      influenced by their own sex and myths about domestic violence, by the victim's
      decision to return to the abusive relationship, and by the relationship status of
      the victim (dating or married to the perpetrator). Results demonstrated
      significant main effects of participant's sex, domestic violence myths, and of
      the victim's relationship status and decision to return. That is, participants
      blamed the victim who reportedly returned to her abuser more than the victim
      about whom there is no such information. Further, participants with greater
      domestic violence myths tended to blame the victim more than those with less
      myths, and male participants blamed the victim and minimized the incident more
      than female participants. Implications, limitations of the study, and future
      research are discussed.

PMID- 22628383
TI  - Who gets blamed for intimate partner violence? The relative contributions of
      perpetrator sex category, victim confrontation, and observer attitudes.
AB  - The present study examined the effects of perpetrator sex category, victim
      confrontation, observer sex category, and observer attitudes on attributions of
      blame and behavioral stability for partner violence. Data were collected from 728
      college-aged students enrolled at 2 universities in the United States. Results
      demonstrated that males and females attributed less blame and behavioral
      stability to female perpetrators than male perpetrators, especially if the
      perpetrator was provoked. Moreover, attitudes toward women and violence were
      important for predicting attributions, and some of the evidence for observer
      effects was reduced to nonsignificance once these variables were added to the
      model.

PMID- 22628386
TI  - Brain. Editorial.

PMID- 22628387
TI  - An unchanging man faced with changing times.

PMID- 22628381
TI  - The quest for four-dimensional imaging in plant cell biology: it's just a matter
      of time.
AB  - BACKGROUND: Analysis of plant cell dynamics over time, or four-dimensional
      imaging (4-DI), represents a major goal of plant science. The ability to resolve
      structures in the third dimension within the cell or tissue during developmental
      events or in response to environmental or experimental stresses (i.e. 4-DI) is
      critical to our understanding of gene expression, post-expression modulations of
      macromolecules and sub-cellular system interactions. SCOPE: Microscopy-based
      technologies have been profoundly integral to this type of investigation, and new
      and refined microscopy technologies now allow for the visualization of cell
      dynamics with unprecedented resolution, contrast and experimental versatility.
      However, certain realities of light and electron microscopy, choice of specimen
      and specimen preparation techniques limit the scope of readily attaining 4-DI.
      Today, the plant microscopist must use a combinatorial strategy whereby multiple
      microscopy-based investigations are used. Modern fluorescence, confocal laser
      scanning, transmission electron and scanning electron microscopy provide
      effective conduits for synthesizing data detailing live cell dynamics and highly
      resolved snapshots of specific cell structures that will ultimately lead to 4-DI.
      This review provides a synopsis of such technologies available.

PMID- 22628388
TI  - Autosomal dominant congenital spinal muscular atrophy: a true form of spinal
      muscular atrophy caused by early loss of anterior horn cells.
AB  - Autosomal dominant congenital spinal muscular atrophy is characterized by
      predominantly lower limb weakness and wasting, and congenital or early-onset
      contractures of the hip, knee and ankle. Mutations in TRPV4, encoding a cation
      channel, have recently been identified in one large dominant congenital spinal
      muscular atrophy kindred, but the genetic basis of dominant congenital spinal
      muscular atrophy in many families remains unknown. It has been hypothesized that
      differences in the timing and site of anterior horn cell loss in the central
      nervous system account for the variations in clinical phenotype between different
      forms of spinal muscular atrophy, but there has been a lack of neuropathological
      data to support this concept in dominant congenital spinal muscular atrophy. We
      report clinical, electrophysiology, muscle magnetic resonance imaging and
      histopathology findings in a four generation family with typical dominant
      congenital spinal muscular atrophy features, without mutations in TRPV4, and in
      whom linkage to other known dominant neuropathy and spinal muscular atrophy genes
      has been excluded. The autopsy findings in the proband, who died at 14 months of
      age from an unrelated illness, provided a rare opportunity to study the
      neuropathological basis of dominant congenital spinal muscular atrophy. There was
      a reduction in anterior horn cell number in the lumbar and, to a lesser degree,
      the cervical spinal cord, and atrophy of the ventral nerve roots at these levels,
      in the absence of additional peripheral nerve pathology or abnormalities
      elsewhere along the neuraxis. Despite the young age of the child at the time of
      autopsy, there was no pathological evidence of ongoing loss or degeneration of
      anterior horn cells suggesting that anterior horn cell loss in dominant
      congenital spinal muscular atrophy occurs in early life, and is largely complete
      by the end of infancy. These findings confirm that dominant congenital spinal
      muscular atrophy is a true form of spinal muscular atrophy caused by a loss of
      anterior horn cells localized to lumbar and cervical regions early in
      development.

PMID- 22628389
TI  - The Gulf War era multiple sclerosis cohort: age and incidence rates by race, sex
      and service.
AB  - We characterize here a new nationwide incident cohort of multiple sclerosis from
      the US military-veteran population. This cohort provides an update to the only
      other US nationwide incidence study of multiple sclerosis performed during the
      1970s. Medical records and data from the Department of Defense and Department of
      Veterans Affairs for cases of multiple sclerosis who served in the military
      between 1990, the start of the Gulf War era, and 2007 and who were service
      connected for this disorder by the Department of Veterans Affairs from 1990 on,
      were reviewed. A total of 2691 patients were confirmed as having multiple
      sclerosis: 2288 definite, 190 possible, 207 clinically isolated syndrome and six
      neuromyelitis optica. Overall racial categories were White, Black and other,
      which included all Hispanics. There were 1278 White males and 556 females; 360
      Black males and 296 females; and 200 others, 153 (77%) of whom were Hispanic.
      Mean age at onset of 30.7 years did not differ significantly by race or sex. Age
      at onset was 17-50 years in 99%, the same age range as 99% of the military.
      Average annual age specific (age 17-50 years) incidence rates per 100 000 for the
      entire series were 9.6 with 95% confidence interval of 9.3-10.0. Rates for Blacks
      were highest at 12.1 with confidence interval 11.2-13.1, Whites were 9.3
      (interval 8.9-9.8) and others 6.9 (interval 6.0-7.9). For 83 Hispanics defined
      for 2000-07, the rate was 8.2 (interval 6.5-10.1). Much smaller numbers gave
      rates of 3.3 for Asian/Pacific Islanders and 3.1 for native Americans. Rates by
      sex for Whites were 7.3 and 25.8 male and female, respectively, for Blacks 8.4
      and 26.3, and for Hispanics 6.6 and 17.0. Rates by service were high for Air
      Force (10.9) and Army (10.6), medium for Navy (9.1) and Coast Guard (7.9), and
      low for Marines (5.3). Relative risk of multiple sclerosis was 3.39 female:male
      and 1.27 Black:White. These new findings indicate that females of all races now
      have incidence rates for multiple sclerosis some three times those of their male
      counterparts and that among these groups, Blacks have the highest and others
      (probably including Hispanics) the lowest incidence rates regardless of sex or
      service. The low rate for Marines is unexplained. This Gulf War era multiple
      sclerosis cohort provides a unique resource for further study.

PMID- 22628390
TI  - BAP updated guidelines: evidence-based guidelines for the pharmacological
      management of substance abuse, harmful use, addiction and comorbidity:
      recommendations from BAP.
AB  - The British Association for Psychopharmacology guidelines for the treatment of
      substance abuse, harmful use, addiction and comorbidity with psychiatric
      disorders primarily focus on their pharmacological management. They are based
      explicitly on the available evidence and presented as recommendations to aid
      clinical decision making for practitioners alongside a detailed review of the
      evidence. A consensus meeting, involving experts in the treatment of these
      disorders, reviewed key areas and considered the strength of the evidence and
      clinical implications. The guidelines were drawn up after feedback from
      participants. The guidelines primarily cover the pharmacological management of
      withdrawal, short- and long-term substitution, maintenance of abstinence and
      prevention of complications, where appropriate, for substance abuse or harmful
      use or addiction as well management in pregnancy, comorbidity with psychiatric
      disorders and in younger and older people.

PMID- 22628391
TI  - Association between preoperative statin therapy and postoperative change in
      glomerular filtration rate in endovascular aortic surgery.
AB  - BACKGROUND: Acute kidney injury during endovascular aortic repair can result in a
      reduction in the postoperative glomerular filtration rate (GFR). The
      'pleiotropic' effects of statins offer a potential mechanism of reducing the
      postoperative decline in the GFR. We therefore tested the hypothesis that in
      patients undergoing endovascular aortic repair, the GFR decreases less in
      patients taking preoperative statins than in those who do not. METHODS: A cohort
      investigation of 501 consecutive patients who underwent endovascular aortic
      repair between June 2005 and March 2007 in an academic tertiary care centre.
      Multivariable linear regression was used to assess the association between the
      statin use and the postoperative GFR, after adjusting for the baseline GFR and
      other confounding covariables selected using a stepwise criterion. RESULTS: The
      statin use was not associated with a change in the postoperative GFR (P=0.94);
      the difference (95% confidence interval) in the mean postoperative GFR (statins
      minus no statins) was estimated at 0.1 (-3.1, +3.4) ml min(-1) 1.73 m(-2). A
      decrease in the GFR of >= 25% (the threshold to diagnose contrast-induced
      nephropathy) developed in 26 of 192 patients given statins before operation
      (13.5%) compared with 36 of 296 patients who were not taking statins (12.2%).
      CONCLUSIONS: Statin therapy is not associated with a statistically significant
      change in the mean postoperative GFR in patients undergoing endovascular aortic
      surgery, nor a reduction in the risk of a GFR decline of >25%.

PMID- 22628392
TI  - Blockade of spinal nerves inhibits expression of neural growth factor in the
      myocardium at an early stage of acute myocardial infarction in rats.
AB  - BACKGROUND: Neural growth factor (NGF) is required for healing and sprouting of
      cardiac sympathetic and sensory nerves and plays important roles in cardiac
      protection, sustaining cardiac function and regeneration in ischaemic heart
      disease. The overexpression or lack of the NGF could be harmful to the heart. In
      this study, we examined the role of spinal nerves in the modulation of expression
      of the NGF in the myocardium at risk of ischaemia soon after acute myocardial
      infarction in rats. METHODS: Coronary artery occlusion (CAO) was carried out in
      anaesthetized rats with and without preconditioning of blockade of the spinal
      nerves. The expression of the NGF protein and mRNA in the myocardium at risk of
      ischaemia was examined using immunohistochemical assay, enzyme-linked
      immunosorbent assay, and real-time quantitative reverse transcription polymerase
      chain reaction assay. RESULTS: In the left ventricle, immunoreactive cells and
      fibre-like structures were mainly located in the myocardium and in the
      epicardium. The NGF protein expression was increased by two-fold in the
      myocardium at risk of ischaemia during the 60 min of CAO, while the NGF mRNA was
      up-regulated three-fold, at 360 min after acute myocardial infarction. The
      blockade of the spinal nerves completely abolished the up-regulation of the NGF
      in the myocardium (P<0.05). CONCLUSIONS: The spinal nerves innervating the heart
      may play an important role in sustaining the up-regulation of the NGF in the
      myocardium early after acute myocardial infarction, an effect which can be
      inhibited by the blockade of these nerves.

PMID- 22628393
TI  - Patient blood management in Europe.
AB  - Preoperative anaemia is common in patients undergoing orthopaedic and other major
      surgery. Anaemia is associated with increased risks of postoperative mortality
      and morbidity, infectious complications, prolonged hospitalization, and a greater
      likelihood of allogeneic red blood cell (RBC) transfusion. Evidence of the
      clinical and economic disadvantages of RBC transfusion in treating perioperative
      anaemia has prompted recommendations for its restriction and a growing interest
      in approaches that rely on patients' own (rather than donor) blood. These
      approaches are collectively termed 'patient blood management' (PBM). PBM involves
      the use of multidisciplinary, multimodal, individualized strategies to minimize
      RBC transfusion with the ultimate goal of improving patient outcomes. PBM relies
      on approaches (pillars) that detect and treat perioperative anaemia and reduce
      surgical blood loss and perioperative coagulopathy to harness and optimize
      physiological tolerance of anaemia. After the recent resolution 63.12 of the
      World Health Assembly, the implementation of PBM is encouraged in all WHO member
      states. This new standard of care is now established in some centres in the USA
      and Austria, in Western Australia, and nationally in the Netherlands. However,
      there is a pressing need for European healthcare providers to integrate PBM
      strategies into routine care for patients undergoing orthopaedic and other types
      of surgery in order to reduce the use of unnecessary transfusions and improve the
      quality of care. After reviewing current PBM practices in Europe, this article
      offers recommendations supporting its wider implementation, focusing on anaemia
      management, the first of the three pillars of PBM.

PMID- 22628395
TI  - Complete genome sequence of a novel porcine enterovirus strain in China.
AB  - The porcine enteroviruses (PEVs) belong to the family Picornaviridae. We report a
      complete genome sequence of a novel PEV strain that is widely prevalent in pigs
      at least in central and eastern China. The complete genome consists of 7,390
      nucleotides, excluding the 3' poly(A) tail, and has an open reading frame that
      maps between nucleotide positions 812 and 7318 and encodes a 2,168-amino-acid
      polyprotein. Phylogenetic analysis based on the 3CD and VP1 regions reveals that
      this PEV strain belongs to a species of PEV9 but may represent a novel sero
      /genotype in CPE group III. We also report the major findings from bootscan
      analysis based on the whole genomes of PEVs in the present study and those
      available in GenBank.

PMID- 22628394
TI  - Electroacupuncture inhibition of hyperalgesia in an inflammatory pain rat model:
      involvement of distinct spinal serotonin and norepinephrine receptor subtypes.
AB  - BACKGROUND: Although acupuncture analgesia is well documented, its mechanisms
      have not been thoroughly clarified. We previously showed that electroacupuncture
      (EA) activates supraspinal serotonin- and norepinephrine-containing neurones that
      project to the spinal cord. This study investigates the involvement of spinal
      alpha(2)-adrenoceptors (alpha2-ARs) and 5-hydroxytryptamine (serotonin) receptors
      (5-HTRs) in EA effects on an inflammatory pain rat model. METHODS: Inflammatory
      hyperalgesia was induced by injecting complete Freund's adjuvant (CFA, 0.08 ml)
      into the plantar surface of one hind paw and assessed by paw withdrawal latency
      (PWL) to a noxious thermal stimulus. The selective alpha2a-AR antagonist BRL
      44408, alpha2b-AR antagonist imiloxan hydrochloride, 5-HT2B receptor (5-HT2BR)
      antagonist SB204741, 5-HT3R antagonist LY278584, or 5-HT1AR antagonists NAN-190
      hydrobromide, or WAY-100635 were intrathecally administered 20 min before EA or
      sham EA, which was given 2 h post-CFA at acupoint GB30. RESULTS: EA significantly
      increased PWL compared with sham [7.20 (0.46) vs 5.20 (0.43) s]. Pretreatment
      with alpha2a-AR [5.35 (0.45) s] or 5-HT1AR [5.22 (0.38) s] antagonists blocked EA
      produced anti-hyperalgesia; alpha2b-AR, 5-HT2BR, and 5-HT3R antagonist
      pretreatment did not. Sham plus these antagonists did not significantly change
      PWL compared with sham plus vehicle, indicating that the antagonists had little
      effect on PWL. Immunohistochemical staining demonstrated that alpha2a-ARs are on
      primary afferents and 5-HT1ARs are localized in N-methyl-d-aspartic acid (NMDA)
      subunit NR1-containing neurones in the spinal dorsal horn. CONCLUSIONS: The data
      show that alpha2a-ARs and 5-HT1ARs are involved in the EA inhibition of
      inflammatory pain and that the NMDA receptors are involved in EA action.

PMID- 22628396
TI  - Complete genome sequence of porcine kobuvirus strain WUH1.
AB  - Porcine kobuvirus, an emerging virus, was first identified in Hungary in 2007. We
      report here the complete genome sequence of porcine kobuvirus strain WUH1
      isolated from piglets with severe diarrhea, which will help toward understanding
      the molecular and evolutionary characteristics of the porcine kobuvirus.

PMID- 22628397
TI  - Genome sequence of a reassortant strain of bluetongue virus serotype 23 from
      western India.
AB  - The full genome sequence (19,177 bp) of an Indian strain (IND1988/02) of
      bluetongue virus (BTV) serotype 23 was determined. This virus was isolated from a
      sheep that had been killed during a severe bluetongue outbreak that occurred in
      Rahuri, Maharashtra State, western India, in 1988. Phylogenetic analyses of these
      data demonstrate that most of the genome segments from IND1988/02 belong to the
      major "eastern" BTV topotype. However, genome segment 5 belongs to the major
      "western" BTV topotype, demonstrating that IND1988/02 is a reassortant. This may
      help to explain the increased virulence that was seen during this outbreak in
      1988. Genome segment 5 of IND1988/02 shows >99% sequence identity with some other
      BTV isolates from India (e.g., BTV-3 IND2003/08), providing further evidence of
      the existence and circulation of reassortant strains on the subcontinent.

PMID- 22628398
TI  - Complete genome sequence of a novel marine siphovirus, pVp-1, infecting Vibrio
      parahaemolyticus.
AB  - Among the abundant bacteriophages that belong to the order Caudovirales in the
      ocean, the genome sequences of marine siphoviruses are poorly investigated in
      comparison to those of myo- or podoviruses. Here we report the complete genome
      sequence of Vibrio phage pVP-1, which belongs to the family Siphoviridae and
      infects Vibrio parahaemolyticus ATCC 33844.

PMID- 22628399
TI  - Complete genome sequence of a new-genotype porcine norovirus isolated from
      piglets with diarrhea.
AB  - Noroviruses (NoVs) are members of the family Caliciviridae and are emerging
      enteric pathogens of humans and animals. So far, porcine NoVs have been detected
      exclusively in fecal samples from adult swine without clinical signs. Here we
      report the genome sequence of a NoV strain isolated from piglets with diarrhea.
      Experimental infection of miniature pigs with this porcine NoV-positive fecal
      sample confirmed that this strain can cause diarrhea in piglets. A phylogenetic
      tree based on the predicted amino acid sequence of the complete capsid region
      showed that this strain is separate from known porcine GII strains (GII-11, GII
      18, and GII-19), constituting the sole member of a new branch.

PMID- 22628400
TI  - A novel porcine circovirus type 2a strain, 10JS-2, with eleven-nucleotide
      insertions in the origin of genome replication.
AB  - Here, we report a novel porcine circovirus type 2a (PCV2a) strain with 11
      nucleotides (nt) inserted in the origin of genome replication (Ori). This is the
      first report of a PCV2a strain with nucleotide insertion in Ori. Our study will
      help further epidemiological studies and extend our knowledge of evolutionary
      characteristics of PCV2.

PMID- 22628401
TI  - Complete genome sequence of the first canine circovirus.
AB  - We found a highly divergent circovirus in serum samples from several dogs.
      Phylogenetic analysis indicates that canine circovirus genotype 1 (CaCV-1)
      represents the first circovirus reported in dogs and is genetically most closely
      related to the only known mammalian circovirus, porcine circovirus. Here we
      report the complete genome sequence of the CaCV-1 strain NY214, which will help
      toward understanding the evolutionary and pathogenic characteristics of mammalian
      circoviruses.

PMID- 22628402
TI  - Genome sequence of the first human adenovirus type 14 isolated in China.
AB  - Emergent pathogens may be examined rapidly at high resolution on a molecular
      level using genomics, allowing an understanding of their evolution. China is a
      unique environment for studying pathogens, having a large, dense, and generally
      closed population. Human adenovirus type 14 (HAdV-14) was originally identified
      as an acute respiratory disease (ARD) pathogen in The Netherlands (1955), with a
      second isolation in England (1957). Since then, few reports of this virus
      appeared until an ARD pathogen with a similar genome caused multiple outbreaks in
      the United States (2006 to 2009). This report presents the first genome of HAdV
      B14 isolated in China (2010). As China experienced two recent outbreaks of an
      emergent ARD pathogen, HAdV-B55, containing much of the HAdV-B14 genome, the
      availability of this HAdV-B14 sequence will facilitate studies of the
      epidemiology of these pathogens, as well as provide a foundation for studying
      adenovirus evolution and the genesis of emergent pathogens. These observations
      may be invaluable in predicting possible recombination between wild-type viruses
      and adenoviral gene delivery vectors, including adenovirus vaccines.

PMID- 22628403
TI  - Complete genome sequence of a dengue virus serotype 4 strain isolated in
      Guangdong, China.
AB  - Here we report the first complete genome sequence of a dengue virus serotype 4
      genotype II strain, GZ30, isolated in Guangzhou, Guangdong Province, China, in
      2010. The sequence information provided herein will help us to understand the
      molecular epidemiology of dengue virus and predict the risk of severe diseases in
      mainland China.

PMID- 22628404
TI  - Complete genome sequence of avian bornavirus genotype 1 from a Macaw with
      proventricular dilatation disease.
AB  - Avian bornaviruses (ABV) were first detected and described in 2008. They are the
      etiologic agents of proventricular dilatation disease (PDD), a frequently fatal
      neurologic disease of captive parrots. Seven ABV genogroups have been identified
      worldwide from a variety of sources, and that number may increase as surveillance
      for novel bornaviruses continues. Here, we report the first complete sequence of
      a genogroup 1 avian bornavirus (ABV1).

PMID- 22628405
TI  - Organization of the ambisense genome of the Helicoverpa armigera Densovirus.
AB  - A natural densovirus (DNV) of a serious phytophagous pest, Helicoverpa armigera,
      was isolated. The genome of HaDNV contained 6,039 nucleotides (nt) and included
      inverted terminal repeats (ITRs) of 545 nt with terminal Y-shaped hairpins of 126
      nt. Its DNA sequence and ambisense organization with four typical open reading
      frames (ORFs) demonstrated that it belonged to the genus Densovirus in the
      subfamily Densovirinae of the family Parvoviridae.

PMID- 22628406
TI  - A lost decade: exploring F Scott Fitzgerald's contribution to the illness canon
      through the doctor-nurse series and other healthcare stories of the 1930s.
AB  - F Scott Fitzgerald spent the 1930s writing about illness themes while he
      struggled with tuberculosis, insomnia, alcoholism, heart disease and the mental
      illness of his wife Zelda. During this decade, Fitzgerald published six stories
      that prominently feature hospitals and healthcare professionals. These stories,
      the 'doctor-nurse stories', along with nine additional published stories that
      touch upon medical themes have not previously been investigated as a thematic
      grouping. This paper explores the 1930s stories in the context of Fitzgerald's
      life and career in order to highlight his significant yet previously undervalued
      contribution to the canon of illness literature and his work's relevance to the
      field of literature and medicine.

PMID- 22628408
TI  - Forced mitotic entry of S-phase cells as a therapeutic strategy induced by
      inhibition of WEE1.
AB  - Inhibition of the protein kinase WEE1 synergizes with chemotherapy in preclinical
      models and WEE1 inhibitors are being explored as potential cancer therapies.
      Here, we investigate the mechanism that underlies this synergy. We show that WEE1
      inhibition forces S-phase-arrested cells directly into mitosis without completing
      DNA synthesis, resulting in highly abnormal mitoses characterized by dispersed
      chromosomes and disorganized bipolar spindles, ultimately resulting in mitotic
      exit with gross micronuclei formation and apoptosis. This mechanism of cell death
      is shared by CHK1 inhibitors, and combined WEE1 and CHK1 inhibition forces
      mitotic entry from S-phase in the absence of chemotherapy. We show that p53/p21
      inactivation combined with high expression of mitotic cyclins and EZH2 predispose
      to mitotic entry during S-phase with cells reliant on WEE1 to prevent premature
      cyclin-dependent kinase (CDK)1 activation. These features are characteristic of
      aggressive breast, and other, cancers for which WEE1 inhibitor combinations
      represent a promising targeted therapy.

PMID- 22628407
TI  - miR-23a promotes the transition from indolent to invasive colorectal cancer.
AB  - Colorectal cancer is a classic example of a tumor that progresses through
      multiple distinct stages in its evolution. To understand the mechanisms
      regulating the transition from indolent to invasive disease, we profiled somatic
      copy number alterations in noninvasive adenomas and invasive adenocarcinomas from
      Apc and DNA mismatch repair (MMR) mutant mouse models. We identified a recurrent
      amplicon on mouse chromosome 8 that encodes microRNA (miRNA) 23a and -27a (miR).
      miR-23a and -27a levels are upregulated in mouse intestinal adenocarcinomas,
      primary tumors from patients with stage I/II colorectal cancers, as well as in
      human colorectal cancer cell lines and cancer stem cells. Functionally, miR-23a
      promotes the migration and invasion of colorectal cancer cells and stem cells,
      whereas miR-27a primarily promotes proliferation. We computationally and
      experimentally validated that metastasis suppressor 1 (MTSS1) is a direct miR-23a
      target and similarly validated that the ubiquitin ligase FBXW7 is a direct miR
      27a target. Analyses of computationally predicted target genes in microarray data
      sets of patients with colorectal cancers are consistent with a role for miR-23a,
      but not miR-27a, specifically in invasive colorectal cancers.

PMID- 22628409
TI  - Gene signatures associated with mouse postnatal hindbrain neural stem cells and
      medulloblastoma cancer stem cells identify novel molecular mediators and predict
      human medulloblastoma molecular classification.
AB  - Medulloblastoma arises from mutations occurring in stem/progenitor cells located
      in restricted hindbrain territories. Here we report that the mouse postnatal
      ventricular zone lining the IV ventricle also harbors bona fide stem cells that,
      remarkably, share the same molecular profile with cerebellar white matter-derived
      neural stem cells (NSC). To identify novel molecular mediators involved in
      medulloblastomagenesis, we compared these distinct postnatal hindbrain-derived
      NSC populations, which are potentially tumor initiating, with murine compound
      Ptch/p53 mutant medulloblastoma cancer stem cells (CSC) that faithfully phenocopy
      the different variants of human medulloblastoma in vivo. Transcriptome analysis
      of both hindbrain NSCs and medulloblastoma CSCs resulted in the generation of
      well-defined gene signatures, each reminiscent of a specific human
      medulloblastoma molecular subclass. Most interestingly, medulloblastoma CSCs
      upregulated developmentally related genes, such as Ebfs, that were shown to be
      highly expressed in human medulloblastomas and play a pivotal role in
      experimental medullo-blastomagenesis. These data indicate that gene expression
      analysis of medulloblastoma CSCs holds great promise not only for understanding
      functional differences between distinct CSC populations but also for identifying
      meaningful signatures that might stratify medulloblastoma patients beyond
      histopathologic staging.

PMID- 22628410
TI  - Evolutionary pathways in BRCA1-associated breast tumors.
AB  - BRCA1-associated breast tumors display loss of BRCA1 and frequent somatic
      mutations of PTEN and TP53. Here we describe the analysis of BRCA1, PTEN, and p53
      at the single cell level in 55 BRCA1-associated breast tumors and computational
      methods to predict the relative temporal order of somatic events, on the basis of
      the frequency of cells with single or combined alterations. Although there is no
      obligatory order of events, we found that loss of PTEN is the most common first
      event and is associated with basal-like subtype, whereas in the majority of
      luminal tumors, mutation of TP53 occurs first and mutant PIK3CA is rarely
      detected. We also observed intratumor heterogeneity for the loss of wild-type
      BRCA1 and increased cell proliferation and centrosome amplification in the normal
      breast epithelium of BRCA1 mutation carriers. Our results have important
      implications for the design of chemopreventive and therapeutic interventions in
      this high-risk patient population.

PMID- 22628411
TI  - A central role for RAF->MEK->ERK signaling in the genesis of pancreatic ductal
      adenocarcinoma.
AB  - KRAS mutation is a hallmark of pancreatic ductal adenocarcinoma (PDA) but remains
      an intractable pharmacologic target. Consequently, defining RAS effector
      pathway(s) required for PDA initiation and maintenance is critical to improve
      treatment of this disease. Here, we show that expression of BRAF(V600E), but not
      PIK3CA(H1047R), in the mouse pancreas leads to pancreatic intraepithelial
      neoplasia (PanIN) lesions. Moreover, concomitant expression of BRAF(V600E) and
      TP53(R270H) result in lethal PDA. We tested pharmacologic inhibitors of RAS
      effectors against multiple human PDA cell lines. Mitogen-activated protein
      (MAP)/extracellular signal-regulated (ERK) kinase (MEK) inhibition was highly
      effective both in vivo and in vitro and was synergistic with AKT inhibition in
      most cell lines tested. We show that RAF->MEK->ERK signaling is central to the
      initiation and maintenance of PDA and to rational combination strategies in this
      disease. These results emphasize the value of leveraging multiple complementary
      experimental systems to prioritize pathways for effective intervention strategies
      in PDA. SIGNIFICANCE: PDA is diffi cult to treat, in large part, due to recurrent
      mutations in the KRAS gene. Here, we defi ne rational treatment approaches for
      the disease achievable today with existing drug combinations by thorough genetic
      and pharmacologic dissection of the major KRAS effector pathways, RAF->MEK->ERK
      and phosphoinositide 3'-kinase (PI3'K)->AKT.

PMID- 22628412
TI  - Palliative cancer care in Middle Eastern countries: accomplishments and
      challenges.
AB  - BACKGROUND: In larger parts of the Middle East palliative care is still
      misunderstood among health professionals, cancer patients and the public at
      large. One reason to that is because the term does not obviously communicate the
      intent of this clinical discipline, which is lending better quality of life while
      combating cancer. Further, culture, tradition and religion have contributed to
      this misgiving and confusion especially at the terminal stage of the disease.
      METHODS: The Middle East Cancer Consortium jointly with the American Society of
      Clinical Oncology, the American Oncology Nursing Society, the San Diego Hospice
      Center for Palliative Medicine and the Children's Hospital & Clinics of Minnesota
      initiated a series of training courses and workshops in the Middle East to
      provide updated training to physicians, nurses, social workers and psychologists
      from throughout the region with basic concepts of palliative care and pain
      managements in adults and children cancers. RESULTS: During the past 6 years
      hundreds of professionals took part in these educational and training activities,
      thereby creating the core of trained caregivers who start to make the change in
      their individual countries. CONCLUSIONS: The outcome of consecutive training
      activities can overcome geopolitical instabilities, and yield a genuine change in
      approach of both regulators, medical administrators, medical staff and the
      public; as to the important contribution of palliative care services to the
      welfare of the patient and his/her family.

PMID- 22628413
TI  - Palliative communications: addressing chemotherapy in patients with advanced
      cancer.
AB  - Patients with advanced cancers often endure chemotherapy late in their disease
      course leading to unnecessary adverse effects, loss of quality of life, and delay
      in hospice referral. Compassionate and honest communication about the use of
      chemotherapy can facilitate better patient care. This manuscript will explore
      communication issues regarding palliative-intent chemotherapy.

PMID- 22628414
TI  - Patient-centered care: the key to cultural competence.
AB  - Much of the early literature on 'cultural competence' focuses on the
      'categorical' or 'multicultural' approach, in which providers learn relevant
      attitudes, values, beliefs, and behaviors of certain cultural groups. In essence,
      this involves learning key 'dos and don'ts' for each group. Literature and
      educational materials of this kind focus on broad ethnic, racial, religious, or
      national groups, such as 'African American', 'Hispanic', or 'Asian'. The problem
      with this categorical or 'list of traits' approach to clinical cultural
      competence is that culture is multidimensional and dynamic. Culture comprises
      multiple variables, affecting all aspects of experience. Cultural processes
      frequently differ within the same ethnic or social group because of differences
      in age cohort, gender, political association, class, religion, ethnicity, and
      even personality. Culture is therefore a very elusive and nebulous concept, like
      art. The multicultural approach to cultural competence results in stereotypical
      thinking rather than clinical competence. A newer, cross cultural approach to
      culturally competent clinical practice focuses on foundational communication
      skills, awareness of cross-cutting cultural and social issues, and health beliefs
      that are present in all cultures. We can think of these as universal human
      beliefs, needs, and traits. This patient centered approach relies on identifying
      and negotiating different styles of communication, decision-making preferences,
      roles of family, sexual and gender issues, and issues of mistrust, prejudice, and
      racism, among other factors. In the current paper, we describe 'cultural'
      challenges that arise in the care of four patients from disparate cultures, each
      of whom has advanced colon cancer that is no longer responding to chemotherapy.
      We then illustrate how to apply principles of patient centered care to these
      challenges.

PMID- 22628416
TI  - Spirituality in the cancer trajectory.
AB  - Spirituality is an essential element of person-centered care and a critical
      factor in the way patients with cancer cope with their illness from diagnosis
      through treatment, survival, recurrence and dying. Studies have indicated a
      significant relationship between spirituality and quality of life. Spirituality,
      in its broadest sense speaks to the meaning patients find in their lives
      especially during times of stress, illness and dying. Illness can trigger deep
      existential issues that could trigger profound suffering and distress. A model is
      presented that describes the role of each member of the healthcare team in
      addressing patients' spirituality. Spiritual distress, as a diagnosis, requires
      attention and treatment just as any other clinical symptom. Spiritual resources
      of strength need to be identifies and recognized as positive factors in patients'
      coping. Finally a treatment plan needs to include the spiritual as well as the
      physical and psychosocial issues of patients. Chaplains and other spiritual care
      professionals need to be recognized as the experts in spiritual care and should
      be integral members of the healthcare team. Integrating spirituality as an
      essential domain of care will result in better health outcomes, particularly
      quality of life for patients across the trajectory of cancer care.

PMID- 22628415
TI  - Palliative oncology: identity, progress, and the path ahead.
AB  - Palliative care is a rapidly growing subspecialty of medicine entailing expert
      and active assessment, evaluation and treatment of the physical, psychological,
      social and spiritual needs of patients and families with serious illnesses. It
      provides an added layer of support to the patient's regular medical care. As
      cancer is detected earlier and its treatments improve, palliative care is
      increasingly playing a vital role in the oncology population. Because of these
      advances in oncology, the role of palliative care services for such patients is
      actively evolving. Herein, we will highlight emerging paradigms in palliative
      care and attempt to delineate key education, research and policy areas that lie
      ahead for the field of palliative oncology. Despite the critical need for
      improving multi-faceted and multi-specialty symptom management and patient
      physician communication, we will focus on the interface between palliative care
      and oncology specialists, a relationship that can lead to better overall patient
      care on all of these levels.

PMID- 22628417
TI  - Death and dying: what the patient wants.
AB  - A good death and a death with dignity may be achieved when death is congruent
      with the personal values of the patient. It behooves the practitioner to
      recognize these values and to cater to them. This paper describes effective
      communication with the dying person, and the partnership of treatment team,
      patient and family in face of the patient death. To identify and define the
      patient wishes it is necessary to learn how to interpret the patient's non verbal
      as often patients are unable to formulate the questions they wish to ask
      concerning their passing. These difficulties stem from several cultural factors
      including concern about disturbing the practitioner. It is the treatment team's
      responsibility to facilitate this discussion. A good death is achieved when
      symptoms are controlled and when patients and family recognize death as a unique
      living experience to be treasured as any other living experience. A death with
      dignity brings healing, that is always possible even when cure is out of reach.
      Patient's and practitioner's values may be at odd in face of controversial issues
      including euthanasia, assisted suicide and terminal sedation. Though he/she
      should not be compelled to execute these requests, the practitioner should be
      able to entertain an open discussion with the patient concerning these issues.
      Open communication and reflective listening even in presence of disagreements are
      the venue of healing. The study of death and dying requires novel approaches
      including personal narrative and qualitative research to complement traditional
      research instrument, such as questionnaire that cannot embrace the whole human
      dimension.

PMID- 22628418
TI  - Cultural diversity: family path through terminal illness.
AB  - In trying to comprehend a culture and its ways of structuring the world, much can
      be learned from addressing the manner in which intimate family relationships are
      ordered and family crises channeled toward care. A family's experience with
      illness cannot be considered in isolation from the cultural milieu in which it
      occurs. Family adaptation to cancer diagnosis is a continuous motion between many
      critical strata--a fragile oscillation between hope and desperation. Processes
      for optimal functioning and the well-being of members are seen to vary over time,
      as challenges unfold and families evolve across the life cycle and illness
      trajectory. The manner in which the healthcare system and family manage illness
      and terminal care is a particularly helpful window into the cultural, religious
      and traditional values of every family in a particular society.

PMID- 22628419
TI  - Cultural beliefs and values in cancer patients.
AB  - In 2008, the International Agency for Research on Cancer (IARC) released its
      World Cancer Report, which indicated that cancer accounts for approximately 12%
      of all-cause mortality worldwide. IARC estimated that globally 7.6 million people
      died from cancer and that 12.4 million new cases were diagnosed in 2008. The
      report went on to project that, due to increases in life expectancy, improvements
      in clinical diagnostics, and shifting trends in health behaviors (e.g. increases
      in smoking and sedentary lifestyles), in the absence of significant efforts to
      improve global cancer control, cancer mortality could increase to 12.9 million
      and cancer incidence to 20 million by the year 2030. Looking deeper into the
      data, it becomes clear that cancer-related stigma and myths about cancer are
      important problems that must be addressed, although different from a country to
      another. Stigmas about cancer present significant challenges to cancer control:
      stigma can have a silencing effect, whereby efforts to increase cancer awareness
      are negatively affected. The social, emotional, and financial devastation that
      all too often accompanies a diagnosis of cancer is, in large part, due to the
      cultural myths and taboos surrounding the disease. Combating stigma, myths,
      taboos, and overcoming silence will play important roles in changing this
      provisional trajectory. There are several reasons that cancer is stigmatized.
      Many people in our area perceived cancer to be a fatal disease. Cancer symptoms
      or body parts affected by the disease can cultivate stigma. Fears about treatment
      can also fuel stigma. There was evidence of myths associated with cancer, such as
      the belief that cancer is contagious, or cancer may be seen as a punishment.
      After reviewing these different examples of cultural myths and taboos met in
      cancer care, we can report these lessons learned: 1. Around the world, cancer
      continues to carry a significant amount of stigma, myths, and taboos; however,
      there are opportunities to capitalize upon shifting perceptions and positive
      change. 2. Awareness of cancer prevention, early detection, treatment, and
      survival are on the rise; however, too many people still report that they feel
      uninformed when it comes to cancer. 3. Communication is critical to decreasing
      cancer-related stigma, raising cancer awareness, and disseminating cancer
      education. People with a personal history of cancer-especially well-known or
      celebrity survivors-and multiple mass media channels are key resources for
      dissemination. 4. The school system represents a potential venue for cancer
      education, and increasing cancer awareness among children may be an investment
      with high returns. 5. When facing cancer, people around the world want
      information and emotional support for themselves and their families. 6. Tobacco
      use and poor nutrition are widely acknowledged as cancer risks. Programs and
      policies that help people translate this awareness into action are needed. The
      global cancer community should capitalize upon positive shifts in attitudes about
      awareness of cancer and leverage these shifts to develop, and disseminate
      effective media campaigns and behavioral interventions to decrease the incidence
      of and morbidity and mortality associated with cancer.

PMID- 22628420
TI  - Practical guidelines for developing new palliative care services: resource
      management.
AB  - The data are relatively clear cut that palliative care improves quality of life
      and symptom control, improves quality of care by reducing aggressive but
      unsuccessful end of life care, and reduces costs. That should be an easy message
      to deliver to the public, health care administrators, payers, and governments. In
      fact, the arguments to develop palliative care services must be clear and
      concise, and make the clinical and financial case for the services that the
      palliative care team wants to deliver. Here, we discuss some of the types of
      models including consult services, outpatient programs, and inpatient units; the
      important components; some easy to use screening tools; components of the
      consultation team; a model medical record that increases "prompts" to do best
      palliative care; and data to report to supervisors.

PMID- 22628421
TI  - Turkish community-based palliative care model: a unique design.
AB  - An organized palliative care system was lacking in Turkey before 2010. One of the
      pillars of Turkish Cancer Control Programme is palliative care. The Pallia-Turk
      project in this respect has been implemented by the Ministry since 2010. The
      project is unique since it is population based and organized at the primary
      level. This means, the whole population (>70 million) will have the quickest and
      easiest way for access to palliative care. This manuscript briefly summarizes the
      situation before the project and updates what has been done in last 2 years with
      the project.

PMID- 22628422
TI  - Physicians' prescribing habits for cancer pain in Cyprus.
AB  - BACKGROUND: Prescription of opioids based on morphine equivalence data per capita
      is very low in Cyprus. Three studies were undertaken to evaluate the prescribing
      habits of physicians in Cyprus for cancer patients with pain. METHODS: Data were
      collected regarding the presence and severity of pain and prescription of
      analgesia in a cross-sectional study of 141 patients receiving outpatient
      chemotherapy within the Bank of Cyprus Oncology Centre (BOCOC), in a
      retrospective study of 90 new lung cancer patients referred to one Oncologist in
      the BOCOC, and in a prospective study of 100 new cancer patients referred to the
      BOCOC. In the first study, the results reflected the prescribing habits of
      oncologists within the oncology centre, whilst the second and third studies
      reflected the prescribing habits of physicians outside the oncology centre.
      RESULTS: In the three studies, 56.0%, 48.1% and 57.7%, respectively, of patients
      with pain were prescribed analgesia. The majority of patients were prescribed
      paracetamol and non-steroidal anti-inflammatory drugs, and only 8.6%, 11.5% and
      0%, respectively, of patients were prescribed strong opioids. In the last two
      studies, following their oncology appointment the prescription of analgesia to
      patients with pain, increased to 80.8% and 73.1%, respectively, whilst the
      prescription of strong opioids, increased to 28.8% and 34.6%, respectively,
      reflecting oncologists' practice. CONCLUSION: There is under-treatment of pain in
      cancer patients, both within and outside a tertiary oncology centre in Cyprus.
      Particularly there is low prescribing of strong opioids. There is a need to look
      further into the barriers that prevent physicians prescribing opioids in Cyprus,
      as well as to patients' attitudes towards analgesia and opioids, and to set up
      training programs to address these issues.

PMID- 22628425
TI  - Kidney tumor biomarkers revealed by simultaneous multiple matrix metabolomics
      analysis.
AB  - Metabolomics is increasingly being used in cancer biology for biomarker discovery
      and identification of potential novel therapeutic targets. However, a systematic
      metabolomics study of multiple biofluids to determine their interrelationships
      and to describe their use as tumor proxies is lacking. Using a mouse xenograft
      model of kidney cancer, characterized by subcapsular implantation of Caki-1 clear
      cell human kidney cancer cells, we examined tissue, serum, and urine all obtained
      simultaneously at baseline (urine) and at, or close to, animal sacrifice (urine,
      tissue, and plasma). Uniform metabolomics analysis of all three "matrices" was
      accomplished using gas chromatography- and liquid chromatography-mass
      spectrometry. Of all the metabolites identified (267 in tissue, 246 in serum, and
      267 in urine), 89 were detected in all 3 matrices, and the majority was altered
      in the same direction. Heat maps of individual metabolites showed that
      alterations in serum were more closely related to tissue than was urine. Two
      metabolites, cinnamoylglycine and nicotinamide, were concordantly and
      significantly (when corrected for multiple testing) altered in tissue and serum,
      and cysteine-glutathione disulfide showed the highest change (232.4-fold in
      tissue) of any metabolite. On the basis of these and other considerations, three
      pathways were chosen for biologic validation of the metabolomic data, resulting
      in potential therapeutic target identification. These data show that serum
      metabolomics analysis is a more accurate proxy for tissue changes than urine and
      that tryptophan degradation (yielding anti-inflammatory metabolites) is highly
      represented in renal cell carcinoma, and support the concept that PPAR-alpha
      antagonism may be a potential therapeutic approach for this disease.

PMID- 22628426
TI  - The Global Cancer Genomics Consortium: interfacing genomics and cancer medicine.
AB  - The Global Cancer Genomics Consortium (GCGC) is an international collaborative
      platform that amalgamates cancer biologists, cutting-edge genomics, and high
      throughput expertise with medical oncologists and surgical oncologists; they
      address the most important translational questions that are central to cancer
      research and treatment. The annual GCGC symposium was held at the Advanced Centre
      for Treatment Research and Education in Cancer, Mumbai, India, from November 9 to
      11, 2011. The symposium showcased international next-generation sequencing
      efforts that explore cancer-specific transcriptomic changes, single-nucleotide
      polymorphism, and copy number variations in various types of cancers, as well as
      the structural genomics approach to develop new therapeutic targets and chemical
      probes. From the spectrum of studies presented at the symposium, it is evident
      that the translation of emerging cancer genomics knowledge into clinical
      applications can only be achieved through the integration of multidisciplinary
      expertise. In summary, the GCGC symposium provided practical knowledge on
      structural and cancer genomics approaches, as well as an exclusive platform for
      focused cancer genomics endeavors.

PMID- 22628427
TI  - CD27 signaling increases the frequency of regulatory T cells and promotes tumor
      growth.
AB  - Signaling of the TNF receptor superfamily member CD27 activates costimulatory
      pathways to elicit T- and B-cell responses. CD27 signaling is regulated by the
      expression of its ligand CD70 on subsets of dendritic cells and lymphocytes.
      Here, we analyzed the role of the CD27-CD70 interaction in the immunologic
      control of solid tumors in Cd27-deficient mice. In tumor-bearing wild-type mice,
      the CD27-CD70 interaction increased the frequency of regulatory T cells (Tregs),
      reduced tumor-specific T-cell responses, increased angiogenesis, and promoted
      tumor growth. CD27 signaling reduced apoptosis of Tregs in vivo and induced
      CD4(+) effector T cells (Teffs) to produce interleukin-2, a key survival factor
      for Tregs. Consequently, the frequency of Tregs and growth of solid tumors were
      reduced in Cd27-deficient mice or in wild-type mice treated with monoclonal
      antibody to block CD27 signaling. Our findings, therefore, provide a novel
      mechanism by which the adaptive immune system enhances tumor growth and may offer
      an attractive strategy to treat solid tumors.

PMID- 22628428
TI  - Roles of purinergic receptor P2Y, G protein-coupled 12 in the development of
      atherosclerosis in apolipoprotein E-deficient mice.
AB  - OBJECTIVE: The aim of the study was to evaluate the role of purinergic receptor
      P2Y, G protein-coupled 12 (P2Y12), an ADP receptor, in the development of
      atherosclerotic lesions. METHODS AND RESULTS: Apolipoprotein E-null mice were
      crossed with P2y12(-/-) mice to generate double knockout mice. The double
      knockout mice and the control apolipoprotein E-null mice were fed a high-fat diet
      for 20 weeks. Assessment of the atherosclerotic lesions in the control and double
      knockout mice demonstrated that P2Y12 deficiency caused a diminished lesion area,
      an increased fibrous content at the plaque site, and decreased
      monocyte/macrophage infiltration of the lesions. Polymerase chain reaction
      studies revealed that white blood cells do not express significant levels of
      P2Y12. Bone marrow transplantation experiments confirmed that P2Y12 expressed on
      platelets is a key factor responsible for atherosclerosis, but do not exclude a
      role of smooth muscle cell P2Y12. Supernatant fluid from activated P2y12(+/+) but
      not P2y12(-/-) platelets was capable of causing monocyte migration. In vitro
      studies showed that platelet P2Y12 deficiency suppressed platelet factor 4
      secretion and P-selectin expression. Further work demonstrated that platelet
      P2Y12, through inhibition of the cAMP/protein kinase A pathway, critically
      regulates the release of platelet factor 4, and thereby affects monocyte
      recruitment and infiltration. CONCLUSIONS: These results demonstrate that P2Y12
      modulates atherogenesis, at least in part by augmenting inflammatory cell
      recruitment via regulation of platelet alpha-granule release.

PMID- 22628429
TI  - Endoluminal gingival fibroblast transfer reduces the size of rabbit carotid
      aneurisms via elastin repair.
AB  - OBJECTIVE: Matrix metalloproteinase-9 is considered to play a pivotal role in
      aneurismal formation. We showed that gingival fibroblasts (GF) in vitro reduced
      matrix metalloproteinase-9 activity via increased secretion of tissue inhibitor
      of metalloproteinase 1. We aimed to evaluate in vivo the efficacy of GF
      transplantation to reduce aneurism development in a rabbit model. METHODS AND
      RESULTS: Seventy rabbit carotid aneurisms were induced by elastase infusion. Four
      weeks later, GF, dermal fibroblast, or culture medium (DMEM) were infused into
      established aneurisms. Viable GF were abundantly detected in the transplanted
      arteries 3 months after seeding. GF engraftment resulted in a significant
      reduction of carotid aneurisms (decrease of 23.3% [P<0.001] and 17.6% [P=0.01] of
      vessel diameter in GF-treated arteries, 1 and 3 months after cell therapy,
      respectively), whereas vessel diameter of control DMEM and dermal fibroblast
      treated arteries increased. GF inhibited matrix metalloproteinase-9 activity by
      tissue inhibitor of metalloproteinase 1 overexpression and matrix
      metalloproteinase-9/tissue inhibitor of metalloproteinase 1 complex formation,
      induced elastin repair, and increased elastin density in the media compared with
      DMEM-treated arteries (38.2 versus 18.0%; P=0.02). Elastin network GF-induced
      repair was inhibited by tissue inhibitor of metalloproteinase 1 blocking peptide.
      CONCLUSIONS: Our results demonstrate that GF transplantation results in
      significant aneurism reduction and elastin repair. This strategy may be
      attractive because GF are accessible and remain viable within the grafted tissue.

PMID- 22628430
TI  - Marked acceleration of atherosclerosis after Lactobacillus casei-induced coronary
      arteritis in a mouse model of Kawasaki disease.
AB  - OBJECTIVE: The purpose of this study was to investigate whether Lactobacillus
      casei cell wall extract-induced Kawasaki disease (KD) accelerates atherosclerosis
      in hypercholesterolemic mice.  Method and Results- Apolipoprotein E knockout or
      low-density lipoprotein receptor knockout mice were injected with Lactobacillus
      casei cell wall extract (KD mice) or PBS, fed high-fat diet for 8 weeks, and
      atherosclerotic lesions in aortic sinuses, arch (AC), and whole aorta were
      assessed. KD mice had larger, more complex aortic lesions with abundant collagen,
      and both extracellular and intracellular lipid and foam cells, compared with
      lesions in control mice despite similar cholesterol levels. Both apolipoprotein E
      knockout KD and low-density lipoprotein receptor knockout KD mice showed dramatic
      acceleration in atherosclerosis versus controls, with increases in en face aortic
      atherosclerosis and plaque size in both the aortic sinuses and AC plaques.
      Accelerated atherosclerosis was associated with increased circulating interleukin
      12p40, interferon-gamma, tumor necrosis factor-alpha, and increased macrophage,
      dendritic cell, and T-cell recruitment in lesions. Furthermore, daily injections
      of the interleukin-1Ra, which inhibits Lactobacillus casei cell wall extract
      induced KD vasculitis, prevented the acceleration of atherosclerosis.
      CONCLUSIONS: Our results suggest an important pathophysiologic link between
      coronary arteritis/vasculitis in the KD mouse model and subsequent
      atherosclerotic acceleration, supporting the concept that a similar relation may
      also be present in KD patients. These results also suggest that KD in childhood
      may predispose to accelerated and early atherosclerosis as adults.

PMID- 22628431
TI  - Extracellular chromatin is an important mediator of ischemic stroke in mice.
AB  - OBJECTIVE: Recently, a growing number of studies have revealed a prothrombotic
      and cytotoxic role for extracellular chromatin. Cerebral ischemia/reperfusion
      injury is characterized by a significant amount of cell death and neutrophil
      activation, both of which may result in the release of chromatin. The goal of
      this study was to assess the effect of extracellular chromatin in ischemic stroke
      using a mouse model of transient middle cerebral artery occlusion. METHODS AND
      RESULTS: Similar to reports in stroke patients, we observed increased levels of
      circulating nucleosomes and DNA after ischemic stroke in mice. In addition, we
      observed that general hypoxia also augmented extracellular chromatin. We
      hypothesized that targeting extracellular chromatin components would be
      protective in ischemic stroke. Indeed, treatment with recombinant human DNase 1
      significantly improved stroke outcome. Neutralization of histones using an
      antihistone antibody was also protective as evidenced by smaller infarct volumes,
      whereas increasing levels of extracellular histones via histone infusion
      exacerbated stroke outcome by increasing infarct size and worsening functional
      outcome. CONCLUSIONS: Our results indicate that extracellular chromatin is
      generated and is detrimental during cerebral ischemia/reperfusion in mice.
      Targeting DNA and histones may be a new therapeutic strategy to limit injury
      resulting from ischemic stroke.

PMID- 22628432
TI  - ABO blood group and von Willebrand factor levels partially explained the
      incomplete penetrance of congenital thrombophilia.
AB  - OBJECTIVE: We aimed to study the association among ABO blood group, von
      Willebrand factor, factor VIII plasma levels, and the risk of venous thrombosis
      (VT) in a cohort of 1774 relatives from 500 families with inherited
      thrombophilia. METHODS AND RESULTS: One hundred sixty-one of the 1774 relatives
      had a VT. Different risk groups were formed: no, low-(factor V Leiden or
      F2G20210A heterozygous carriers), and high-risk thrombophilia (antithrombin,
      protein C, protein S, factor V Leiden, or F2G20210A homozygous carriers and
      combined defects). Compared with group O, AB blood group was associated with
      increased risk of VT: hazard ratio (HR)=3.8 (2.0-7.2). The effect of blood group
      A and B was milder (HR=1.6 [1.1-2.5] and 1.8 [1.0-3.3], respectively). An
      increased risk of VT was observed with increasing levels of von Willebrand factor
      and factor VIII plasma levels (HR=2.96 [1.92-4.56] and HR=2.60 [1.92-4.56] for
      third versus first tertile of von Willebrand factor and factor VIII plasma
      levels, respectively). In multivariate analysis, AB group (HR=2.3 [1.1-4.8]),
      high-risk thrombophilia (HR=2.8 [1.6-4.6]), and high von Willebrand factor levels
      (HR=2.3 [1.3-4.0]) were significantly associated with increased risk of VT. The
      risk of VT in individuals with high-risk thrombophilia and AB group was 14.4*
      higher than in those without thrombophilia and O group (5.0-41.4). CONCLUSIONS:
      ABO blood group modifies the risk of VT in families with hereditary
      thrombophilia. Phenotyping of the ABO blood group should be performed to better
      assess the risk of VT in asymptomatic individuals from thrombophilic families.

PMID- 22628433
TI  - Protein tyrosine phosphatase SHP2 mediates chronic insulin-induced endothelial
      inflammation.
AB  - OBJECTIVE: Insulin promotes adhesion of leukocytes to the endothelium through
      increased expression of surface adhesion molecules. We determined whether src
      homology domain-2-containing protein tyrosine phosphatase 2 (SHP2), a downstream
      effecter of insulin signaling, is involved in insulin-induced endothelial
      inflammation. METHODS AND RESULTS: In human umbilical vein-derived endothelial
      cells, treatment with insulin (100 nmol/L) increased Tyr(542) phosphorylation,
      activity, and subsequently expression of SHP2. Increase in SHP2 accompanied a
      parallel decrease in the availability of the anti-inflammatory molecule, NO. This
      consequently enhanced the expression of cell adhesion molecules. Decrease in NO
      index was caused by endothelial NO synthase (eNOS) uncoupling and increased
      arginase activity. Among the 2 isoforms, insulin treatment induced the expression
      of arginase II. Inactivation of endogenous SHP2 via NSC87877 [8-hydroxy-7-(6
      sulfonapthalen-2-yl)-diazenyl-quinoline-5-sulfonic acid] and its knockdown by
      small interfering RNA decreased arginase activity by blocking arginase II
      expression; however, it failed to restore eNOS coupling. Inactivation of SHP2
      also abrogated insulin-mediated leukocyte adhesion by blocking the expression of
      adhesion molecules. Finally, downregulation of endogenous arginase II blocked
      insulin-mediated endothelial inflammation. CONCLUSIONS: SHP2 mediates chronic
      insulin-induced endothelial inflammation by limiting the production of NO in an
      eNOS-independent and arginase-II-dependent manner.

PMID- 22628434
TI  - Low levels of circulating CD4+FoxP3+ T cells are associated with an increased
      risk for development of myocardial infarction but not for stroke.
AB  - OBJECTIVE: Regulatory T cells (Tregs) protect against atherosclerosis in
      experimental models, but their association with cardiovascular disease in humans
      remains to be elucidated. The aim of the present study was to determine whether
      circulating Tregs predict the development of acute cardiovascular events in
      humans. METHODS AND RESULTS: The study cohort consisted of a random sample of
      participants (n=700), aged 68 to 73 years, from the Malmo Diet and Cancer Study.
      Mononuclear leukocytes, stored at -140 degrees C at the baseline investigation in
      1991-1994, were thawed and Tregs, defined by the expression of FoxP3 in CD4+ T
      cells, were analyzed by flow cytometry. There was no detectable loss of cells
      during storage, and the viability of thawed leukocytes was 95%. A low fraction of
      both CD4+FoxP3+ and CD4+CD25+FoxP3+ T cells was associated with a higher release
      of proinflammatory cytokines from activated mononuclear leukocytes, and this
      association was strongest for CD4+FoxP3+ cells. Eighty-four coronary events and
      66 strokes were registered during follow-up until December 31, 2008. In a Cox
      proportional hazard regression model adjusting for major risk factors, low levels
      of baseline CD4+FoxP3+ T cells were associated with an increased risk for the
      development of acute coronary events but not stroke. There were no associations
      between CD4+CD25+FoxP3+ T cells and development of an acute coronary event or
      stroke. CONCLUSIONS: This study provides prospective evidence for the role of
      Tregs in the development of myocardial infarction. The findings are in accordance
      with previous experimental studies and provide clinical support for a protective
      role of Tregs in atherosclerosis. The lack of association between Tregs and
      stroke may reflect the more heterogeneous cause of this disease.

PMID- 22628436
TI  - Association of SCARB1 variants with subclinical atherosclerosis and incident
      cardiovascular disease: the multi-ethnic study of atherosclerosis.
AB  - OBJECTIVE: We previously reported a statistically significant association of
      SCARB1 intronic single nucleotide polymorphism (SNP) rs10846744 with common
      carotid intimal-medial artery thickness in each of the 4 Multi-Ethnic Study of
      Atherosclerosis racial/ethnic groups (white, Chinese, black, and Hispanic).
      METHODS AND RESULTS: Using an expanded sample of 7936 Multi-Ethnic Study of
      Atherosclerosis participants, phenotyped for measures of subclinical
      atherosclerosis, incident myocardial infarction, and cardiovascular disease, and
      genotyped through the SNP Health Association Resource project, we have now
      examined the genetic association of these phenotypes with 126 genotyped and
      imputed SCARB1 SNPs. We also performed stratified analyses to examine whether
      SCARB1 SNP effects differed by sex. Our analysis of the full Multi-Ethnic Study
      of Atherosclerosis cohort provides strong evidence for the association of
      rs10846744 with common carotid intimal-medial thickness (P=1.04E-4 in combined
      analysis of all 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups). In
      sex-stratified analysis, we observed statistically significant association of
      rs10846744 with incident cardiovascular disease events in males (P=0.01).
      Examining analytical results from the Myocardial Infarction Genetics Consortium
      for replication, we observed further support for the association of rs10846744
      with myocardial infarction. CONCLUSIONS: The SCARB1 SNP, rs10846744, exerts a
      major effect on subclinical atherosclerosis and incident cardiovascular disease
      in humans.

PMID- 22628435
TI  - Angiopoietin-1 and vascular endothelial growth factor regulation of leukocyte
      adhesion to endothelial cells: role of nuclear receptor-77.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) promotes leukocyte adhesion
      to endothelial cells (ECs). Angiopoietin-1 (Ang-1) inhibits this response.
      Nuclear receptor-77 (Nur77) is a proangiogenic nuclear receptor. In the present
      study, we assessed the influence of Ang-1 and VEGF on Nur77 expression in ECs,
      and evaluated its role in Ang-1/VEGF-mediated leukocyte adhesion. METHODS AND
      RESULTS: Expression of Nur77 was evaluated with real-time polymerase chain
      reaction and immunoblotting. Adhesion of leukocytes to ECs was monitored with
      inverted microscopy. Nur77 expression or activity was inhibited using
      adenoviruses expressing dominant-negative form of Nur77, retroviruses expressing
      Nur77 in the antisense direction, and small interfering RNA oligos. Both Ang-1
      and VEGF induce Nur77 expression, by >5- and 30-fold, respectively. When
      combined, Ang-1 potentiates VEGF-induced Nur77 expression. Ang-1 induces Nur77
      through the phosphoinositide 3-kinase and extracellular signal-regulated protein
      kinase 1/2 pathways. VEGF induces Nur77 expression through the protein kinase
      D/histone deacetylase 7/myocyte enhancer factor 2 and extracellular signal
      regulated protein kinase 1/2 pathways. VEGF induces nuclear factor-kappaB
      transcription factor, vascular cell adhesion molecule-1, and E-selectin
      expressions, and promotes leukocyte adhesion to ECs. Ang-1 inhibits these
      responses. This inhibitory effect of Ang-1 disappears when Nur77 expression is
      disrupted, restoring the inductive effects of VEGF on adhesion molecule
      expression, and increased leukocyte adhesion to ECs. CONCLUSIONS: Nur77 promotes
      anti-inflammatory effects of Ang-1, and functions as a negative feedback
      inhibitor of VEGF-induced EC activation.

PMID- 22628437
TI  - Blocking toll-like receptors 7 and 9 reduces postinterventional remodeling via
      reduced macrophage activation, foam cell formation, and migration.
AB  - OBJECTIVE: The role of toll-like receptors (TLRs) in vascular remodeling is well
      established. However, the involvement of the endosomal TLRs is unknown. Here, we
      study the effect of combined blocking of TLR7 and TLR9 on postinterventional
      remodeling and accelerated atherosclerosis. METHODS AND RESULTS: In
      hypercholesterolemic apolipoprotein E*3-Leiden mice, femoral artery cuff
      placement led to strong increase of TLR7 and TLR9 presence demonstrated by
      immunohistochemistry. Blocking TLR7/9 with a dual antagonist in vivo reduced
      neointimal thickening and foam cell accumulation 14 days after surgery by 65.6%
      (P=0.0079). Intima/media ratio was reduced by 64.5% and luminal stenosis by
      62.8%. The TLR7/9 antagonist reduced the arterial wall inflammation, with reduced
      macrophage infiltration, decreased cytoplasmic high-mobility group box 1
      expression, and altered serum interleukin-10 levels. Stimulation of cultured
      macrophages with TLR7 and TLR9 ligands enhanced tumor necrosis factor-alpha
      expression, which is decreased by TLR7/9 antagonist coadministration.
      Additionally, the antagonist abolished the TLR7/9-enhanced low-density
      lipoprotein uptake. The antagonist also reduced oxidized low-density lipoprotein
      induced foam cell formation, most likely not via decreased influx but via
      increased efflux, because CD36 expression was unchanged whereas interleukin-10
      levels were higher (36.1 +/- 22.3 pg/mL versus 128.9 +/- 6.6 pg/mL; P=0.008).
      CONCLUSIONS: Blocking TLR7 and TLR9 reduced postinterventional vascular
      remodeling and foam cell accumulation indicating TLR7 and TLR9 as novel
      therapeutic targets.

PMID- 22628438
TI  - Microvolt T-wave alternans testing should be used to guide arrhythmic therapy in
      heart failure patients.

PMID- 22628440
TI  - The isolation, loneliness and helplessness of being homeless.

PMID- 22628445
TI  - Looking into the neonatal isolette.

PMID- 22628449
TI  - Mechanical regulation of cellular phenotype: implications for vascular tissue
      regeneration.
AB  - Cells sense a myriad of cues from their surrounding microenvironment to regulate
      their function. In recent years, it has become clear that physical and mechanical
      cues are as critical as biochemical factors in regulating cellular function. The
      geometry of the extracellular matrix (ECM), degree of cell spreading, and ECM
      rigidity all influence the physical connection between cells and their
      microenvironment and play a major role in regulating proliferation,
      differentiation, and migration. Leveraging these findings to promote specific
      cell behaviours will be paramount to realize the full potential of cellular
      therapies. In this review, I examine our current understanding of how mechanical
      cues-specifically, geometric control of cell shape and matrix rigidity-are
      transduced by stem cells to control their stemness, proliferation, and
      differentiation. The implications of these findings for vascular smooth muscle
      cell differentiation and cardiovascular tissue engineering will be highlighted.

PMID- 22628451
TI  - Absent proximal right coronary artery with a fistula into the pulmonary vein.
AB  - A 32-year-old woman was admitted with a third-degree atrioventricular block. A
      permanent pacemaker was implanted and the patient was discharged. One week later,
      the patient presented again with a sustained ventricular tachycardia. Coronary
      angiography and computed tomography imaging with three-dimensional
      reconstructions revealed the absence of the proximal part of the right coronary
      artery (RCA) with a fistula into the pulmonary vein. This is the first case
      describing an absent proximal RCA combined with a pulmonary vein fistula.

PMID- 22628453
TI  - Comparison of pacing algorithms to avoid unnecessary ventricular pacing in
      patients with sick sinus node syndrome: a single-centre, observational, parallel
      study.
AB  - AIMS: Reduction of unnecessary ventricular pacing (uVP) is an essential component
      in the treatment strategy in any pacing population in general. The aim of this
      study was to evaluate the efficacy of different algorithms to reduce uVP in an
      adult population with sick sinus syndrome (SSS) treated outside of clinical
      trials. Evaluation of the relationship between different types of pacing
      algorithms and clinical outcomes is also provided. METHODS AND RESULTS: This was
      a single-centre, observational, parallel study, based on retrospective analysis
      of the Arrhythmology Cardiology Center of Armenia electronic clinical database.
      This study evaluated atrial pacing percentage (AP%), ventricular pacing
      percentage (VP%), and the incidence of atrial high rate episodes in 56 patients
      with SSS using three different pacing strategies: managed VP, search
      atrioventricular (AV), and fixed long AV. We did not find statistically
      significant differences in the amount of VP between the groups. Although the
      atrial high rate percentage (AHR%) tended to be higher in the fixed long AV
      group, this difference was not statistically significant. Mean VP% and AP% were
      similar in all three groups. CONCLUSIONS: In our study, all three programmed
      strategies produced the same mean AP% and VP%, and were equally efficient in uVP
      reduction. There was no relationship between chosen algorithms and the incidence
      of pacemaker syndrome, hospitalizations, or change in New York Heart Association
      class. The percentage of AHR was not associated with pacing strategy or co
      morbidities but showed borderline correlation with left atrial size.

PMID- 22628454
TI  - Potential molecular tools for assessing the public health risk associated with
      waterborne Cryptosporidium oocysts.
AB  - The use of multiple barrier stages at water and wastewater treatment facilities
      allows for the effective removal of the vast majority of coliforms and other
      enteric and non-enteric microbes. Subsequent disinfection steps (chlorine, ozone
      and UV irradiation) are utilized to inactivate microbes that escape the preceding
      treatment stages. Most viruses, bacteria and protozoa, such as Giardia, are
      effectively inactivated by chlorination; however, Cryptosporidium is relatively
      more resistant to environmental conditions and to chlorination. Therefore, UV
      disinfection has been introduced at many water and wastewater treatment plants to
      increase log inactivation. Any accidental treatment failure may pose a
      significant risk to public health. Waterborne transmission of coccidian parasites
      such as Cryptosporidium and Giardia continues to be a major public health
      concern. No effective therapies currently exist to treat cryptosporidiosis and
      the global increase in immunocompromised populations has emphasized the need for
      water utilities and public health laboratories to have immediate and reliable
      access to highly sensitive test methods that can determine the host specificity,
      viability and infectivity of protozoa in the water supply. The most common method
      used for monitoring Cryptosporidium oocysts and Giardia cysts at intermediate
      treatment stages and in finished drinking water is the US EPA Method 1623.
      Although Cryptosporidium species are morphologically indistinguishable, they
      differ greatly in their host specificity and infectivity. Method 1623 provides
      quantitative information about Cryptosporidium and Giardia contamination but
      cannot distinguish between species for intervention purposes in outbreak
      situations, nor is this method reliable for determining whether the oocyst on the
      slide is infective for humans. Molecular methods have proven valuable in
      diagnosing infectious diseases, especially those for which the causative agent is
      difficult to grow in culture, and similar tools would aid public health agencies
      to determine risk associated with Cryptosporidium. This review focuses on current
      methods for determining the host specificity (genotyping), viability and
      infectivity of Cryptosporidium oocysts.

PMID- 22628455
TI  - Septicaemia caused by Arcanobacterium haemolyticum smooth type in an
      immunocompetent patient.
AB  - Arcanobacterium haemolyticum is a rarely reported human pathogen but can cause
      wound infections in elderly patients with immunodeficiency and
      pharyngotonsillitis in adolescents and young adults. A. haemolyticum septicaemia
      originating from a wound rarely occurs and mainly affects immunocompromised
      patients. Here, we report a case of A. haemolyticum septicaemia in an
      immunocompetent patient with no underlying diseases.

PMID- 22628456
TI  - Carbapenemase-producing Acinetobacter baumannii in two university hospitals in
      Algeria.

PMID- 22628457
TI  - Content and timing of antenatal care: predisposing, enabling and pregnancy
      related determinants of antenatal care trajectories.
AB  - BACKGROUND: When examining risk factors for inadequate antenatal care, the
      assessment of antenatal care hardly considers the content and timing of
      interventions during pregnancy. This study aims to provide information about the
      importance of predisposing, enabling and pregnancy-related determinants on the
      received content and timing of antenatal care. METHODS: In the Brussels
      Metropolitan Region, 333 women were consecutively recruited at the beginning of
      their pregnancies. Antenatal care use was recorded prospectively. A
      classification system measuring the content and timing of care during pregnancy
      (CTP) divided the women into four categories. Ordinal regression analyses were
      applied to define unadjusted and adjusted odds ratios (ORs), measuring the effect
      of different determinants on being assigned to a higher CTP category. RESULTS: A
      total of 10.2% of the women had an inadequate, 8.4% an intermediate, 36% a
      sufficient and 45.3% an appropriate antenatal care trajectory. Adjusted ORs
      showed a lower likelihood of being assigned to a higher CTP category for lower
      educated women (OR: 0.58; 95% CI 0.37-0.92), women of Maghreb origin (OR: 0.38;
      95% CI 0.22-0.66) and women with a higher discontinuity of care (OR: 0.56; 95% CI
      0.34-0.90). CONCLUSIONS: When controlling for confounders, no enabling
      determinants were found that affect the content and timing of care in pregnancy.
      Although antenatal care is equally available to all women, predisposing and
      pregnancy-related factors were related to the likelihood of completing an
      appropriate antenatal care trajectory. Besides stimulating knowledge about the
      importance of antenatal care in less-educated and Maghreb women, supporting
      continuity of care during pregnancy might result in higher levels of received
      antenatal care.

PMID- 22628450
TI  - ESC-EURObservational Research Programme: the Atrial Fibrillation Ablation Pilot
      Study, conducted by the European Heart Rhythm Association.
AB  - AIMS: The Atrial Fibrillation Ablation Pilot Study is a prospective,
      multinational registry conducted by the European Heart Rhythm Association of the
      European Society of Cardiology that has been designed to describe the clinical
      epidemiology of patients undergoing an atrial fibrillation (AFib) ablation
      procedure, and the diagnostic/therapeutic processes applied in these patients
      across Europe. We present the results of the short-term (in-hospital) analysis.
      METHODS AND RESULTS: A total of 72 centres in 10 European countries were asked to
      enrol 20 consecutive patients scheduled for a first AFib ablation procedure.
      Between October 2010 and May 2011, 1410 patients were included, of which 1391
      underwent an AFib ablation (98.7%). The median age was 60 years [inter-quartile
      range (IQR) 52-66], and 28% were females. Two-thirds presented paroxysmal AFib
      and 38% lone AFib. Symptoms were present in 86%. The indications for ablation
      were mostly symptomatic AFib, but in over a third of patients there was also a
      desire for a drug-free lifestyle and the maintenance of sinus rhythm. Pulmonary
      vein isolation was attempted in 98.4% of patients, the roof line in 21.3% and the
      mitral isthmus line in 12.8%. Complex-fractionated atrial electrograms were
      targeted in 17.9% and the ganglionated plexi in 3.3%. Complications occurred in
      7.7%, of which 1.7% was major (i.e. cardiac perforation, myocardial infraction,
      endocarditis, cardiac arrest, stroke, hemothorax, pneumothorax, and sepsis). The
      median duration of hospitalization was 3 days (IQR 2-4). At discharge, 91.4% of
      patients were in sinus rhythm, 88.3% of patients were given vitamin K
      antagonists, and 67% antiarrhythmic medication. There was one death after the
      ablation procedure. CONCLUSION: The AFib Ablation Pilot Study provides crucial
      information on AF ablation in clinical practice across Europe. These data are
      relevant for further improvement of the management strategies of patients
      suffering from atrial fibrillation.

PMID- 22628458
TI  - The development of multisensory integration in high-functioning autism: high
      density electrical mapping and psychophysical measures reveal impairments in the
      processing of audiovisual inputs.
AB  - Successful integration of auditory and visual inputs is crucial for both basic
      perceptual functions and for higher-order processes related to social cognition.
      Autism spectrum disorders (ASD) are characterized by impairments in social
      cognition and are associated with abnormalities in sensory and perceptual
      processes. Several groups have reported that individuals with ASD are impaired in
      their ability to integrate socially relevant audiovisual (AV) information, and it
      has been suggested that this contributes to the higher-order social and cognitive
      deficits observed in ASD. However, successful integration of auditory and visual
      inputs also influences detection and perception of nonsocial stimuli, and
      integration deficits may impair earlier stages of information processing, with
      cascading downstream effects. To assess the integrity of basic AV integration, we
      recorded high-density electrophysiology from a cohort of high-functioning
      children with ASD (7-16 years) while they performed a simple AV reaction time
      task. Children with ASD showed considerably less behavioral facilitation to
      multisensory inputs, deficits that were paralleled by less effective neural
      integration. Evidence for processing differences relative to typically developing
      children was seen as early as 100 ms poststimulation, and topographic analysis
      suggested that children with ASD relied on different cortical networks during
      this early multisensory processing stage.

PMID- 22628459
TI  - An epilepsy-related ARX polyalanine expansion modifies glutamatergic neurons
      excitability and morphology without affecting GABAergic neurons development.
AB  - Epileptic encephalopathies comprise a heterogeneous group of severe infantile
      disorders for which the pathophysiological basis of epilepsy is inaccurately
      clarified by genotype-phenotype analysis. Because a deficit of GABA neurons has
      been found in some of these syndromes, notably in patients with X-linked
      lissencephaly with abnormal genitalia, epilepsy was suggested to result from an
      imbalance in GABAergic inhibition, and the notion of "interneuronopathy" was
      proposed. Here, we studied the impact of a polyalanine expansion of aristaless
      related homeobox (ARX) gene, a mutation notably found in West and Ohtahara
      syndromes. Analysis of Arx((GCG)7/Y) knock-in mice revealed that GABA neuron
      development is not affected. Moreover, pyramidal cell migration and cortical
      layering are unaltered in these mice. Interestingly, electrophysiological
      recordings show that hippocampal pyramidal neurons displayed a frequency of
      inhibitory postsynaptic currents similar to wild-type (WT) mice. However, these
      neurons show a dramatic increase in the frequency of excitatory inputs associated
      with a remodeling of their axonal arborization, suggesting that epilepsy in
      Arx((GCG)7/Y)mice would result from a glutamate network remodeling. We therefore
      propose that secondary alterations are instrumental for the development of
      disease-specific phenotypes and should be considered to explain the phenotypic
      diversity associated with epileptogenic mutations.

PMID- 22628460
TI  - Molecular diversity of early-born subplate neurons.
AB  - Subplate cells in the mouse are generally defined as cells located in the
      subplate layer between the white matter and layer 6a. They are some of the
      earliest born and maturing cells of the cerebral cortex. The postnatal subplate
      layer in mouse contains neurons with expression of the presynaptic protein
      complexin 3 (Cplx3), connective tissue growth factor (CTGF), the orphan nuclear
      receptor Nr4a2 (Nurr1), and the G-protein-coupled lysophosphatidic acid receptor
      1 (Lpar1/Edg2). All 4 of these molecular markers show layer 6b-restricted
      expression at young postnatal ages, with CTGF expression being the most
      widespread in the young postnatal subplate. However, all 4 markers overlap in
      their expression pattern to varying degrees. Here we demonstrate with
      bromodeoxyuridine birthdating that cells labeled with any 1 of these molecular
      subplate markers are indeed generated at E11.5 or E12.5 in the mouse.
      Furthermore, we demonstrate a correlation between gene expression and cell
      birthdates. Lpar1-GFP cells are preferentially generated on E11.5, whereas Cplx3
      or Nurr1-positive cells are equally generated during the 2-day peak of subplate
      neurogenesis (E11.5-E12.5). Our study also demonstrates that early-born subplate
      neurons labeled by Cplx3, Nurr1, and Lpar1-GFP survive preferentially after the
      first postnatal week compared with other subplate neurons.

PMID- 22628461
TI  - Evidence for widespread GC-biased gene conversion in eukaryotes.
AB  - GC-biased gene conversion (gBGC) is a process that tends to increase the GC
      content of recombining DNA over evolutionary time and is thought to explain the
      evolution of GC content in mammals and yeasts. Evidence for gBGC outside these
      two groups is growing but is still limited. Here, we analyzed 36 completely
      sequenced genomes representing four of the five major groups in eukaryotes
      (Unikonts, Excavates, Chromalveolates and Plantae). gBGC was investigated by
      directly comparing GC content and recombination rates in species where
      recombination data are available, that is, half of them. To study all species of
      our dataset, we used chromosome size as a proxy for recombination rate and
      compared it with GC content. Among the 17 species showing a significant
      relationship between GC content and chromosome size, 15 are consistent with the
      predictions of the gBGC model. Importantly, the species showing a pattern
      consistent with gBGC are found in all the four major groups of eukaryotes
      studied, which suggests that gBGC may be widespread in eukaryotes.

PMID- 22628462
TI  - Abnormal developmental control of replication-timing domains in pediatric acute
      lymphoblastic leukemia.
AB  - Abnormal replication timing has been observed in cancer but no study has
      comprehensively evaluated this misregulation. We generated genome-wide
      replication-timing profiles for pediatric leukemias from 17 patients and three
      cell lines, as well as normal B and T cells. Nonleukemic EBV-transformed
      lymphoblastoid cell lines displayed highly stable replication-timing profiles
      that were more similar to normal T cells than to leukemias. Leukemias were more
      similar to each other than to B and T cells but were considerably more
      heterogeneous than nonleukemic controls. Some differences were patient specific,
      while others were found in all leukemic samples, potentially representing early
      epigenetic events. Differences encompassed large segments of chromosomes and
      included genes implicated in other types of cancer. Remarkably, differences that
      distinguished leukemias aligned in register to the boundaries of developmentally
      regulated replication-timing domains that distinguish normal cell types. Most
      changes did not coincide with copy-number variation or translocations. However,
      many of the changes that were associated with translocations in some leukemias
      were also shared between all leukemic samples independent of the genetic lesion,
      suggesting that they precede and possibly predispose chromosomes to the
      translocation. Altogether, our results identify sites of abnormal developmental
      control of DNA replication in cancer that reveal the significance of replication
      timing boundaries to chromosome structure and function and support the
      replication domain model of replication-timing regulation. They also open new
      avenues of investigation into the chromosomal basis of cancer and provide a
      potential novel source of epigenetic cancer biomarkers.

PMID- 22628463
TI  - Extinction and ecological retreat in a community of primates.
AB  - The lemurs of Madagascar represent a prodigious adaptive radiation. At least 17
      species ranging from 11 to 160 kg have become extinct during the past 2000 years.
      The effect of this loss on contemporary lemurs is unknown. The concept of
      competitive release favours the expansion of living species into vacant niches.
      Alternatively, factors that triggered the extinction of some species could have
      also reduced community-wide niche breadth. Here, we use radiocarbon and stable
      isotope data to examine temporal shifts in the niches of extant lemur species
      following the extinction of eight large-bodied species. We focus on southwestern
      Madagascar and report profound isotopic shifts, both from the time when now
      extinct lemurs abounded and from the time immediately following their decline to
      the present. Unexpectedly, the past environments exploited by lemurs were drier
      than the protected (albeit often degraded) riparian habitats assumed to be ideal
      for lemurs today. Neither competitive release nor niche contraction can explain
      these observed trends. We develop an alternative hypothesis: ecological retreat,
      which suggests that factors surrounding extinction may force surviving species
      into marginal or previously unfilled niches.

PMID- 22628464
TI  - Modelling the interaction of keratinocytes and fibroblasts during normal and
      abnormal wound healing processes.
AB  - The crosstalk between fibroblasts and keratinocytes is a vital component of the
      wound healing process, and involves the activity of a number of growth factors
      and cytokines. In this work, we develop a mathematical model of this crosstalk in
      order to elucidate the effects of these interactions on the regeneration of
      collagen in a wound that heals by second intention. We consider the role of four
      components that strongly affect this process: transforming growth factor-beta,
      platelet-derived growth factor, interleukin-1 and keratinocyte growth factor. The
      impact of this network of interactions on the degradation of an initial fibrin
      clot, as well as its subsequent replacement by a matrix that is mainly composed
      of collagen, is described through an eight-component system of nonlinear partial
      differential equations. Numerical results, obtained in a two-dimensional domain,
      highlight key aspects of this multifarious process, such as re-epithelialization.
      The model is shown to reproduce many of the important features of normal wound
      healing. In addition, we use the model to simulate the treatment of two
      pathological cases: chronic hypoxia, which can lead to chronic wounds; and
      prolonged inflammation, which has been shown to lead to hypertrophic scarring. We
      find that our model predictions are qualitatively in agreement with previously
      reported observations and provide an alternative pathway for gaining insight into
      this complex biological process.

PMID- 22628465
TI  - Outsourcing punishment to God: beliefs in divine control reduce earthly
      punishment.
AB  - The sanctioning of norm-transgressors is a necessary--though often costly--task
      for maintaining a well-functioning society. Prior to effective and reliable
      secular institutions for punishment, large-scale societies depended on
      individuals engaging in 'altruistic punishment'--bearing the costs of punishment
      individually, for the benefit of society. Evolutionary approaches to religion
      suggest that beliefs in powerful, moralizing Gods, who can distribute rewards and
      punishments, emerged as a way to augment earthly punishment in large societies
      that could not effectively monitor norm violations. In five studies, we
      investigate whether such beliefs in God can replace people's motivation to engage
      in altruistic punishment, and their support for state-sponsored punishment.
      Results show that, although religiosity generally predicts higher levels of
      punishment, the specific belief in powerful, intervening Gods reduces altruistic
      punishment and support for state-sponsored punishment. Moreover, these effects
      are specifically owing to differences in people's perceptions that humans are
      responsible for punishing wrongdoers.

PMID- 22628466
TI  - Long-term demographic consequences of a seed dispersal disruption.
AB  - The loss or decline of vertebrate frugivores can limit the regeneration of plants
      that depend on them. However, empirical evidence is showing that this is still
      very scarce, as functionally equivalent species may contribute to maintain the
      mutualistic interaction. Here, we investigated the long-term consequences of the
      extinction of frugivorous lizards on the population persistence of a
      Mediterranean relict shrub Cneorum tricoccon (Cneoraceae). We examined the
      demographic parameters among 26 insular and mainland populations, which encompass
      the entire plant distributional range, comparing populations with lizards with
      those in which these are extinct, but in which alien mammals currently act as
      seed dispersers. Plant recruitment was found to be higher on island populations
      with lizards than on those with mammals, and the long-term effects of the native
      disperser's loss were found in all vital phases of plant regeneration. The study
      thus gives evidence of the cascading effects of human-induced changes in
      ecosystems, showing how the disruption of native ecological processes can lead to
      species regression and, in the long term, even to local extinctions.

PMID- 22628467
TI  - Phylogeny versus body size as determinants of food web structure.
AB  - Food webs are the complex networks of trophic interactions that stoke the
      metabolic fires of life. To understand what structures these interactions in
      natural communities, ecologists have developed simple models to capture their
      main architectural features. However, apparently realistic food webs can be
      generated by models invoking either predator-prey body-size hierarchies or
      evolutionary constraints as structuring mechanisms. As a result, this approach
      has not conclusively revealed which factors are the most important. Here we cut
      to the heart of this debate by directly comparing the influence of phylogeny and
      body size on food web architecture. Using data from 13 food webs compiled by
      direct observation, we confirm the importance of both factors. Nevertheless,
      phylogeny dominates in most networks. Moreover, path analysis reveals that the
      size-independent direct effect of phylogeny on trophic structure typically
      outweighs the indirect effect that could be captured by considering body size
      alone. Furthermore, the phylogenetic signal is asymmetric: closely related
      species overlap in their set of consumers far more than in their set of
      resources. This is at odds with several food web models, which take only the view
      point of consumers when assigning interactions. The echo of evolutionary history
      clearly resonates through current food webs, with implications for our
      theoretical models and conservation priorities.

PMID- 22628468
TI  - Out of the Neotropics: Late Cretaceous colonization of Australasia by American
      arthropods.
AB  - The origins of tropical southwest Pacific diversity are traditionally attributed
      to southeast Asia or Australia. Oceanic and fragment islands are typically
      colonized by lineages from adjacent continental margins, resulting in attrition
      of diversity with distance from the mainland. Here, we show that an exceptional
      tropical family of harvestmen with a trans-Pacific disjunct distribution has its
      origin in the Neotropics. We found in a multi-locus phylogenetic analysis that
      the opilionid family Zalmoxidae, which is distributed in tropical forests on both
      sides of the Pacific, is a monophyletic entity with basal lineages endemic to
      Amazonia and Mesoamerica. Indo-Pacific Zalmoxidae constitute a nested clade,
      indicating a single colonization event. Lineages endemic to putative source
      regions, including Australia and New Guinea, constitute derived groups.
      Divergence time estimates and probabilistic ancestral area reconstructions
      support a Neotropical origin of the group, and a Late Cretaceous (ca 82 Ma)
      colonization of Australasia out of the Fiji Islands and/or Borneo, which are
      consistent with a transoceanic dispersal event. Our results suggest that the
      endemic diversity within traditionally defined zoogeographic boundaries might
      have more complex evolutionary origins than previously envisioned.

PMID- 22628469
TI  - A cascade of evolutionary change alters consumer-resource dynamics and ecosystem
      function.
AB  - It is becoming increasingly clear that intraspecific evolutionary divergence
      influences the properties of populations, communities and ecosystems. The
      different ecological impacts of phenotypes and genotypes may alter selection on
      many species and promote a cascade of ecological and evolutionary change
      throughout the food web. Theory predicts that evolutionary interactions across
      trophic levels may contribute to hypothesized feedbacks between ecology and
      evolution. However, the importance of 'cascading evolutionary change' in a
      natural setting is unknown. In lakes in Connecticut, USA, variation in migratory
      behaviour and feeding morphology of a fish predator, the alewife (Alosa
      pseudoharengus), drives life-history evolution in a species of zooplankton prey
      (Daphnia ambigua). Here we evaluated the reciprocal impacts of Daphnia evolution
      on ecological processes in laboratory mesocosms. We show that life-history
      evolution in Daphnia facilitates divergence in rates of population growth, which
      in turn significantly alters consumer-resource dynamics and ecosystem function.
      These experimental results parallel trends observed in lakes. Such results argue
      that a cascade of evolutionary change, which has occurred over contemporary
      timescales, alters community and ecosystem processes.

PMID- 22628471
TI  - Tetrapod-like axial regionalization in an early ray-finned fish.
AB  - Tetrapods possess up to five morphologically distinct vertebral series: cervical,
      thoracic, lumbar, sacral and caudal. The evolution of axial regionalization has
      been linked to derived Hox expression patterns during development and the demands
      of weight-bearing and walking on land. These evolutionary and functional
      explanations are supported by an absence of similar traits in fishes, living and
      extinct. Here, I show that, Tarrasius problematicus, a marine ray-finned fish
      from the Mississippian (Early Carboniferous; 359-318 Ma) of Scotland, is the
      first non-tetrapod known to possess tetrapod-like axial regionalization.
      Tarrasius exhibits five vertebral regions, including a seven-vertebrae 'cervical'
      series and a reinforced 'sacrum' over the pelvic area. Most vertebrae possess
      processes for intervertebral contact similar to tetrapod zygapophyses. The fully
      aquatic Tarrasius evolved these morphologies alongside other traits convergent
      with early tetrapods, including a naked trunk, and a single median continuous
      fin. Regional modifications in Tarrasius probably facilitated pelagic swimming,
      rather than a terrestrial lifestyle or walking gait, presenting an alternative
      scenario for the evolution of such traits in tetrapods. Axial regionalization in
      Tarrasius could indicate tetrapod-like Hox expression patterns, possibly
      representing the primitive state for jawed vertebrates. Alternately, it could
      signal a weaker relationship, or even a complete disconnect, between Hox
      expression domains and vertebrate axial plans.

PMID- 22628470
TI  - Phylogenomic datasets provide both precision and accuracy in estimating the
      timescale of placental mammal phylogeny.
AB  - The fossil record suggests a rapid radiation of placental mammals following the
      Cretaceous-Paleogene (K-Pg) mass extinction 65 million years ago (Ma);
      nevertheless, molecular time estimates, while highly variable, are generally much
      older. Early molecular studies suffer from inadequate dating methods, reliance on
      the molecular clock, and simplistic and over-confident interpretations of the
      fossil record. More recent studies have used Bayesian dating methods that
      circumvent those issues, but the use of limited data has led to large estimation
      uncertainties, precluding a decisive conclusion on the timing of mammalian
      diversifications. Here we use a powerful Bayesian method to analyse 36 nuclear
      genomes and 274 mitochondrial genomes (20.6 million base pairs), combined with
      robust but flexible fossil calibrations. Our posterior time estimates suggest
      that marsupials diverged from eutherians 168-178 Ma, and crown Marsupialia
      diverged 64-84 Ma. Placentalia diverged 88-90 Ma, and present-day placental
      orders (except Primates and Xenarthra) originated in a ~20 Myr window (45-65 Ma)
      after the K-Pg extinction. Therefore we reject a pre K-Pg model of placental
      ordinal diversification. We suggest other infamous instances of mismatch between
      molecular and palaeontological divergence time estimates will be resolved with
      this same approach.

PMID- 22628472
TI  - Timing in a fluctuating environment: environmental variability and asymmetric
      fitness curves can lead to adaptively mismatched avian reproduction.
AB  - Adaptation in dynamic environments depends on the grain, magnitude and
      predictability of ecological fluctuations experienced within and across
      generations. Phenotypic plasticity is a well-studied mechanism in this regard,
      yet the potentially complex effects of stochastic environmental variation on
      optimal mean trait values are often overlooked. Using an optimality model
      inspired by timing of reproduction in great tits, we show that temporal variation
      affects not only optimal reaction norm slope, but also elevation. With increased
      environmental variation and an asymmetric relationship between fitness and
      breeding date, optimal timing shifts away from the side of the fitness curve with
      the steepest decline. In a relatively constant environment, the timing of the
      birds is matched with the seasonal food peak, but they become adaptively
      mismatched in environments with temporal variation in temperature whenever the
      fitness curve is asymmetric. Various processes affecting the survival of
      offspring and parents influence this asymmetry, which collectively determine the
      'safest' strategy, i.e. whether females should breed before, on, or after the
      food peak in a variable environment. As climate change might affect the
      (co)variance of environmental variables as well as their averages, risk aversion
      may influence how species should shift their seasonal timing in a warming world.

PMID- 22628473
TI  - Insect phylogenomics: results, problems and the impact of matrix composition.
AB  - In this study, we investigated the relationships among insect orders with a main
      focus on Polyneoptera (lower Neoptera: roaches, mantids, earwigs, grasshoppers,
      etc.), and Paraneoptera (thrips, lice, bugs in the wide sense). The relationships
      between and within these groups of insects are difficult to resolve because only
      few informative molecular and morphological characters are available. Here, we
      provide the first phylogenomic expressed sequence tags data ('EST': short sub
      sequences from a c(opy) DNA sequence encoding for proteins) for stick insects
      (Phasmatodea) and webspinners (Embioptera) to complete published EST data. As
      recent EST datasets are characterized by a heterogeneous distribution of
      available genes across taxa, we use different rationales to optimize the data
      matrix composition. Our results suggest a monophyletic origin of Polyneoptera and
      Eumetabola (Paraneoptera + Holometabola). However, we identified artefacts of
      tree reconstruction (human louse Pediculus humanus assigned to Odonata
      (damselflies and dragonflies) or Holometabola (insects with a complete
      metamorphosis); mayfly genus Baetis nested within Neoptera), which were most
      probably rooted in a data matrix composition bias due to the inclusion of
      sequence data of entire proteomes. Until entire proteomes are available for each
      species in phylogenomic analyses, this potential pitfall should be carefully
      considered.

PMID- 22628474
TI  - A broader model for C4 photosynthesis evolution in plants inferred from the
      goosefoot family (Chenopodiaceae s.s.).
AB  - C(4) photosynthesis is a fascinating example of parallel evolution of a complex
      trait involving multiple genetic, biochemical and anatomical changes. It is seen
      as an adaptation to deleteriously high levels of photorespiration. The current
      scenario for C(4) evolution inferred from grasses is that it originated
      subsequent to the Oligocene decline in CO(2) levels, is promoted in open
      habitats, acts as a pre-adaptation to drought resistance, and, once gained, is
      not subsequently lost. We test the generality of these hypotheses using a dated
      phylogeny of Amaranthaceae s.l. (including Chenopodiaceae), which includes the
      largest number of C(4) lineages in eudicots. The oldest chenopod C(4) lineage
      dates back to the Eocene/Oligocene boundary, representing one of the first
      origins of C(4) in plants, but still corresponding with the Oligocene decline of
      atmospheric CO(2). In contrast to grasses, the rate of transitions from C(3) to
      C(4) is highest in ancestrally drought resistant (salt-tolerant and succulent)
      lineages, implying that adaptation to dry or saline habitats promoted the
      evolution of C(4); and possible reversions from C(4) to C(3) are apparent. We
      conclude that the paradigm established in grasses must be regarded as just one
      aspect of a more complex system of C(4) evolution in plants in general.

PMID- 22628475
TI  - A Middle Jurassic abelisaurid from Patagonia and the early diversification of
      theropod dinosaurs.
AB  - Abelisaurids are a clade of large, bizarre predatory dinosaurs, most notable for
      their high, short skulls and extremely reduced forelimbs. They were common in
      Gondwana during the Cretaceous, but exceedingly rare in the Northern Hemisphere.
      The oldest definitive abelisaurids so far come from the late Early Cretaceous of
      South America and Africa, and the early evolutionary history of the clade is
      still poorly known. Here, we report a new abelisaurid from the Middle Jurassic of
      Patagonia, Eoabelisaurus mefi gen. et sp. nov., which predates the so far oldest
      known secure member of this lineage by more than 40 Myr. The almost complete
      skeleton reveals the earliest evolutionary stages of the distinctive features of
      abelisaurids, such as the modification of the forelimb, which started with a
      reduction of the distal elements. The find underlines the explosive radiation of
      theropod dinosaurs in the Middle Jurassic and indicates an unexpected diversity
      of ceratosaurs at that time. The apparent endemism of abelisauroids to southern
      Gondwana during Pangean times might be due to the presence of a large, central
      Gondwanan desert. This indicates that, apart from continent-scale geography,
      aspects such as regional geography and climate are important to reconstruct the
      biogeographical history of Mesozoic vertebrates.

PMID- 22628476
TI  - Bringing together linguistic and genetic evidence to test the Bantu expansion.
AB  - The expansion of Bantu languages represents one of the most momentous events in
      the history of Africa. While it is well accepted that Bantu languages spread from
      their homeland (Cameroon/Nigeria) approximately 5000 years ago (ya), there is no
      consensus about the timing and geographical routes underlying this expansion. Two
      main models of Bantu expansion have been suggested: The 'early-split' model
      claims that the most recent ancestor of Eastern languages expanded north of the
      rainforest towards the Great Lakes region approximately 4000 ya, while the 'late
      split' model proposes that Eastern languages diversified from Western languages
      south of the rainforest approximately 2000 ya. Furthermore, it is unclear whether
      the language dispersal was coupled with the movement of people, raising the
      question of language shift versus demic diffusion. We use a novel approach taking
      into account both the spatial and temporal predictions of the two models and
      formally test these predictions with linguistic and genetic data. Our results
      show evidence for a demic diffusion in the genetic data, which is confirmed by
      the correlations between genetic and linguistic distances. While there is little
      support for the early-split model, the late-split model shows a relatively good
      fit to the data. Our analyses demonstrate that subsequent contact among
      languages/populations strongly affected the signal of the initial migration via
      isolation by distance.

PMID- 22628477
TI  - Rhabdom evolution in butterflies: insights from the uniquely tiered and
      heterogeneous ommatidia of the Glacial Apollo butterfly, Parnassius glacialis.
AB  - The eye of the Glacial Apollo butterfly, Parnassius glacialis, a 'living fossil'
      species of the family Papilionidae, contains three types of spectrally
      heterogeneous ommatidia. Electron microscopy reveals that the Apollo rhabdom is
      tiered. The distal tier is composed exclusively of photoreceptors expressing
      opsins of ultraviolet or blue-absorbing visual pigments, and the proximal tier
      consists of photoreceptors expressing opsins of green or red-absorbing visual
      pigments. This organization is unique because the distal tier of other known
      butterflies contains two green-sensitive photoreceptors, which probably function
      in improving spatial and/or motion vision. Interspecific comparison suggests that
      the Apollo rhabdom retains an ancestral tiered pattern with some modification to
      enhance its colour vision towards the long-wavelength region of the spectrum.

PMID- 22628480
TI  - Lethality and cooperation of Pseudomonas aeruginosa quorum-sensing mutants in
      Drosophila melanogaster infection models.
AB  - The virulence profiles of Pseudomonas aeruginosa quorum-sensing (QS) mutants were
      assessed in Drosophila melanogaster feeding and nicking infection models.
      Functional RhlIR and LasIR QS systems were required for killing in the fly
      feeding infection model but were not essential in the fly nicking infection
      model. Mixed infections between PAO1 and strains harbouring mutations in lasR,
      rhlI and lasI rhlI resulted in increased lethality in the fly feeding model
      compared with either isolate alone. These results suggested that the parental
      strain could cooperate with QS mutants in the Drosophila feeding infection model.
      Finally, the mixed infection between PAO1 and an rhlR mutant resulted in spiteful
      behaviour and reduced pathogenicity of the mixed culture.

PMID- 22628478
TI  - Intergenerational relationship quality across three generations.
AB  - OBJECTIVES: Studies of intergenerational relationship quality often include one
      or two generations. This study examined within-family differences and
      similarities or transmission of positive and negative relationship quality across
      three generations. METHOD: Participants included 633 middle-aged individuals (G2;
      52% women, ages 40-60 years), 592 of their offspring (G3; 53% daughters; ages 18
      41 years), and 337 of their parents (i.e., grandparents; G1; 69% women; ages 59
      96 years). RESULTS: Multilevel models revealed differences and similarities in
      relationship quality across generations. The oldest generation (G1) reported
      greater positive and less negative quality relationships than the middle (G2) and
      the younger (G3) generations. There was limited evidence of transmission. Middle
      aged respondents who reported more positive and less negative ties with their
      parents (G1) reported more positive and less negative ties with their own
      children (G3). Grandmother (G1) reports of more positive relationship quality
      were associated with G3 reports of more positive relationship quality with G2.
      DISCUSSION: Findings are consistent with the intergenerational stake hypothesis
      and only partially consistent with the theory of intergenerational transmission.
      Overall, this study suggests that there is greater within-family variability than
      similarities in how family members feel about one another.

PMID- 22628479
TI  - The Bordetella pertussis model of exquisite gene control by the global
      transcription factor BvgA.
AB  - Bordetella pertussis causes whooping cough, an infectious disease that is
      reemerging despite widespread vaccination. A more complete understanding of B.
      pertussis pathogenic mechanisms will involve unravelling the regulation of its
      impressive arsenal of virulence factors. Here we review the action of the B.
      pertussis response regulator BvgA in the context of what is known about bacterial
      RNA polymerase and various modes of transcription activation. At most virulence
      gene promoters, multiple dimers of phosphorylated BvgA (BvgA~P) bind upstream of
      the core promoter sequence, using a combination of high- and low-affinity sites
      that fill through cooperativity. Activation by BvgA~P is typically mediated by a
      novel form of class I/II mechanisms, but two virulence genes, fim2 and fim3,
      which encode serologically distinct fimbrial subunits, are regulated using a
      previously unrecognized RNA polymerase/activator architecture. In addition, the
      fim genes undergo phase variation because of an extended cytosine (C) tract
      within the promoter sequences that is subject to slipped-strand mispairing during
      replication. These sophisticated systems of regulation demonstrate one aspect
      whereby B. pertussis, which is highly clonal and lacks the extensive genetic
      diversity observed in many other bacterial pathogens, has been highly successful
      as an obligate human pathogen.

PMID- 22628481
TI  - Cardiolipin biosynthesis in Streptococcus mutans is regulated in response to
      external pH.
AB  - Streptococcus mutans, a causative agent of dental caries in humans, adapts to
      changing environmental conditions, such as pH, in order to survive and cause
      disease in the oral cavity. Previously, we have shown that S. mutans increases
      the proportion of monounsaturated membrane fatty acids as part of its acid
      adaptive strategy. Membrane lipids function as carriers of membrane fatty acids
      and therefore it was hypothesized that lipid backbones themselves could
      participate in the acid adaptation process. Lipids have been shown to protect
      other bacterial species from rapid changes in their environment, such as shifts
      in osmolality and the need for long-term survival. In the present study, we have
      determined the contribution of cardiolipin (CL) to acid resistance in S. mutans.
      Two ORFs have been identified in the S. mutans genome that encode presumptive
      synthetic enzymes for the acidic phospholipids: phosphatidylglycerol (PG)
      synthase (pgsA, SMU.2151c) and CL synthase (cls, SMU.988), which is responsible
      for condensing two molecules of PG to create CL. A deletion mutant of the
      presumptive cls gene was created using PCR-mediated cloning; however, attempts to
      delete pgsA were unsuccessful, indicating that pgsA may be essential. Loss of the
      presumptive cls gene resulted in the inability of the mutant strain to produce
      CL, indicating that SMU.988 encodes CL synthase. The defect in cls rendered the
      mutant acid sensitive, indicating that CL is required for acid adaptation in S.
      mutans. Addition of exogenous CL to the mutant strain alleviated acid
      sensitivity. MS indicated that S. mutans could assimilate exogenous CL into the
      membrane, halting endogenous CL incorporation. This phenomenon was not due to
      repression, as a cls gene transcriptional reporter fusion exhibited elevated
      activity when cells were supplemented with exogenous CL. Lipid analysis, via MS,
      indicated that CL is a reservoir for monounsaturated fatty acids in S. mutans. We
      demonstrated that the cls mutant exhibits elevated F-ATPase activity but it is
      nevertheless unable to maintain the normal membrane proton gradient, indicating
      cytoplasmic acidification. We conclude that the control of lipid backbone
      synthesis is part of the acid-adaptive repertoire of S. mutans.

PMID- 22628483
TI  - A bacterial two-hybrid genome fragment library for deciphering regulatory
      networks of the opportunistic pathogen Pseudomonas aeruginosa.
AB  - Bacterial gene regulation is controlled by complex regulatory cascades which
      integrate input environmental signals and adapt specific and adequate output
      cellular responses. These complex networks are far from being elucidated, in
      particular in Pseudomonas aeruginosa. In the present study, we developed
      bacterial two-hybrid genome fragment libraries of the P. aeruginosa PAO1 strain
      to identify potential partners involved in the HptB/HsbR/HsbA pathway. This
      powerful tool, validated by the interaction previously described between HsbR and
      HsbA proteins, allowed us to demonstrate that the HsbR response regulator
      dimerizes through its PP2C/ATPase C-terminal effector domain, an observation
      further confirmed by pull-down experiments. This will also allow us to identify
      further new partners in this cascade.

PMID- 22628482
TI  - Roles of H2 uptake hydrogenases in Shigella flexneri acid tolerance.
AB  - Hydrogenases play many roles in bacterial physiology, and use of H(2) by the
      uptake-type enzymes of animal pathogens is of particular interest. Hydrogenases
      have never been studied in the pathogen Shigella, so targeted mutant strains were
      individually generated in the two Shigella flexneri H(2)-uptake enzymes (Hya and
      Hyb) and in the H(2)-evolving enzyme (Hyc) to address their roles. Under
      anaerobic fermentative conditions, a Hya mutant strain (hya) was unable to
      oxidize H(2), while a Hyb mutant strain oxidized H(2) like the wild-type. A hyc
      strain oxidized more exogenously added hydrogen than the parent. Fluorescence
      ratio imaging with dye JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'
      tetraethylbenzimidazolylcarbocyanine iodide) showed that the parent strain
      generated a membrane potential 15 times greater than hya. The hya mutant was also
      by far the most acid-sensitive strain, being even more acid-sensitive than a
      mutant strain in the known acid-combating glutamate-dependent acid-resistance
      pathway (GDAR pathway). In severe acid-challenge experiments, the addition of
      glutamate to hya restored survivability, and this ability was attributed in part
      to the GDAR system (removes intracellular protons) by mutant strain (e.g.
      hya/gadBC double mutant) analyses. However, mutant strain phenotypes indicated
      that a larger portion of the glutamate-rescued acid tolerance was independent of
      GadBC. The acid tolerance of the hya strains was aided by adding chloride ions to
      the growth medium. The whole-cell Hya enzyme became more active upon acid
      exposure (20 min), based on assays of hyc. Indeed, the very high rates of
      Shigella H(2) oxidation by Hya in acid can supply each cell with 2.4*10(8)
      protons min(-1). Electrons generated from Hya-mediated H(2) oxidation at the
      inner membrane likely counteract cytoplasmic positive charge stress, while
      abundant proton pools deposited periplasmically likely repel proton influx during
      severe acid stress.

PMID- 22628484
TI  - An oscillating Min system in Bacillus subtilis influences asymmetrical septation
      during sporulation.
AB  - The Min system plays an important role in ensuring that cell division occurs at
      mid-cell in rod-shaped bacteria. In Escherichia coli, pole-to-pole oscillation of
      the Min proteins specifically inhibits polar septation. This system also prevents
      polar division in Bacillus subtilis during vegetative growth; however, the Min
      proteins do not oscillate in this organism. The Min system of B. subtilis plays a
      distinct role during sporulation, a process of differentiation which begins with
      an asymmetrical cell division. Here, we show that oscillation of the E. coli Min
      proteins can be reproduced following their introduction into B. subtilis cells.
      Further, we present evidence that the oscillatory behaviour of the Min system
      inhibits sporulation. We propose that an alternative Min system mechanism
      avoiding oscillation is evolutionarily important because oscillation of the Min
      system is incompatible with efficient asymmetrical septum formation and
      sporulation.

PMID- 22628486
TI  - Extensive variation in surface lipoprotein gene content and genomic changes
      associated with virulence during evolution of a novel North American house finch
      epizootic strain of Mycoplasma gallisepticum.
AB  - Mycoplasma gallisepticum, a significant respiratory and reproductive pathogen of
      domestic poultry, has since 1994 been recognized as an emergent pathogen of the
      American house finch (Carpodacus mexicanus). Epizootic spread and pathognomonic
      characteristics of house finch-associated Mycoplasma gallisepticum (HFMG) have
      been studied as a model of an emergent to endemic pathogen in a novel host. Here
      we present comparative analysis of eight HFMG genomes, including one from an
      index isolate and seven isolates separated spatially and temporally (1994-2008)
      across the epizootic, and notably having differences in virulence. HFMG
      represented a monophyletic clade relative to sequenced poultry isolates, with
      genomic changes indicating a novel M. gallisepticum lineage and including unique
      deletions of coding sequence. Though most of the HFMG genome was highly conserved
      among isolates, genetic distances correlated with temporal-spatial distance from
      the index. The most dramatic genomic differences among HFMG involved phase
      variable and immunodominant VlhA lipoprotein genes, including those variable in
      presence and genomic location. Other genomic differences included tandem copy
      number variation of a 5 kbp repeat, changes in and adjacent to the clustered
      regularly interspaced short palindromic repeats, and small-scale changes
      affecting coding potential and association of genes with virulence. Divergence of
      monophyletic isolates from similar time/space in the epizootic indicated local
      diversification of distinct HFMG sublineages. Overall, these data identify
      candidate virulence genes and reveal the importance of phase-variable
      lipoproteins during the evolution of M. gallisepticum during its emergence and
      dissemination in a novel host in nature, likely mediating an important role at
      the interface between pathogen virulence and host immunity.

PMID- 22628485
TI  - Mycobacterium tuberculosis RecG binds and unwinds model DNA substrates with a
      preference for Holliday junctions.
AB  - The RecG enzyme, a superfamily 2 helicase, is present in nearly all bacteria.
      Here we report for the first time that the recG gene is also present in the
      genomes of most vascular plants as well as in green algae, but is not found in
      other eukaryotes or archaea. The precise function of RecG is poorly understood,
      although ample evidence shows that it plays critical roles in DNA repair,
      recombination and replication. We further demonstrate that Mycobacterium
      tuberculosis RecG (RecG(Mtb)) DNA binding activity had a broad substrate
      specificity, whereas it only unwound branched-DNA substrates such as Holliday
      junctions (HJs), replication forks, D-loops and R-loops, with a strong preference
      for the HJ as a helicase substrate. In addition, RecG(Mtb) preferentially bound
      relatively long (>=40 nt) ssDNA, exhibiting a higher affinity for the
      homopolymeric nucleotides poly(dT), poly(dG) and poly(dC) than for poly(dA).
      RecG(Mtb) helicase activity was supported by hydrolysis of ATP or dATP in the
      presence of Mg(2+), Mn(2+), Cu(2+) or Fe(2+). Like its Escherichia coli
      orthologue, RecG(Mtb) is also a strictly DNA-dependent ATPase.

PMID- 22628487
TI  - Quantitative computerized two-point correlation analysis of lung CT scans
      correlates with pulmonary function in pulmonary sarcoidosis.
AB  - BACKGROUND: Chest CT scans are commonly used to clinically assess disease
      severity in patients presenting with pulmonary sarcoidosis. Despite their ability
      to reliably detect subtle changes in lung disease, the utility of chest CT scans
      for guiding therapy is limited by the fact that image interpretation by
      radiologists is qualitative and highly variable. We sought to create a
      computerized CT image analysis tool that would provide quantitative and
      clinically relevant information. METHODS: We established that a two-point
      correlation analysis approach reduced the background signal attendant to normal
      lung structures, such as blood vessels, airways, and lymphatics while
      highlighting diseased tissue. This approach was applied to multiple lung fields
      to generate an overall lung texture score (LTS) representing the quantity of
      diseased lung parenchyma. Using deidentified lung CT scan and pulmonary function
      test (PFT) data from The Ohio State University Medical Center's Information
      Warehouse, we analyzed 71 consecutive CT scans from patients with sarcoidosis for
      whom simultaneous matching PFTs were available to determine whether the LTS
      correlated with standard PFT results. RESULTS: We found a high correlation
      between LTS and FVC, total lung capacity, and diffusing capacity of the lung for
      carbon monoxide (P < .0001 for all comparisons). Moreover, LTS was equivalent to
      PFTs for the detection of active lung disease. The image analysis protocol was
      conducted quickly (< 1 min per study) on a standard laptop computer connected to
      a publicly available National Institutes of Health ImageJ toolkit. CONCLUSIONS:
      The two-point image analysis tool is highly practical and appears to reliably
      assess lung disease severity. We predict that this tool will be useful for
      clinical and research applications.

PMID- 22628488
TI  - Clinical significance of the differentiation between Mycobacterium avium and
      Mycobacterium intracellulare in M avium complex lung disease.
AB  - BACKGROUND: Mycobacterium avium and Mycobacterium intracellulare are grouped
      together as the M avium complex; however, little is known about the clinical
      impact of this species differentiation. This study compared the clinical features
      and prognoses of patients with M avium and M intracellulare lung disease.
      METHODS: From 2000 to 2009, 590 patients were given a new diagnosis of M avium
      complex lung disease; 323 (55%) had M avium lung disease, and 267 (45%) had M
      intracellulare lung disease. RESULTS: Compared with the patients with M avium
      lung disease, the patients with M intracellulare lung disease were more likely to
      have the following characteristics: older age (64 vs 59 years, P = .002), a lower
      BMI (19.5 kg/m2 vs 20.6 kg/m2, P < .001), respiratory symptoms such as cough (84%
      vs 74%, P = .005), a history of previous treatment for TB (51% vs 31%, P < .001),
      the fibrocavitary form of the disease (26% vs 13%, P < .001), smear-positive
      sputum (56% vs 38%, P < .001), antibiotic therapy during the 24 months of follow
      up (58% vs 42%, P < .001), and an unfavorable microbiologic response after
      combination antibiotic treatment (56% vs 74%, P = .001). CONCLUSIONS: Patients
      with M intracellulare lung disease exhibited a more severe presentation and had a
      worse prognosis than patients with M avium lung disease in terms of disease
      progression and treatment response. Therefore, species differentiation between M
      avium and M intracellulare may have prognostic and therapeutic implications.

PMID- 22628489
TI  - Protective effects of FCGR2A polymorphism in invasive pneumococcal diseases.
AB  - BACKGROUND: Streptococcus pneumoniae is a major cause of pneumonia and
      meningitis. Several genetic polymorphisms have been described to explain
      differences in susceptibility and severity of encapsulated pathogen-related
      diseases. Among them, a functional FCGR2A polymorphism leading to amino acid
      change of histidine (H) to arginine (R) at position 131 appears to be a major
      candidate in adult invasive pneumococcal diseases (IPDs). However, previous
      reports need confirmation in a large, well-defined population. METHODS: This
      prospective genetic association study was carried out in a 24-bed medical ICU of
      a tertiary teaching hospital over 7 years. DNA from all white patients with IPD
      (pneumonia or meningitis) was genotyped for the FcgammaRIIa-R/H131 polymorphism.
      RESULTS: A total of 243 patients with IPD were enrolled; 202 (82%) had pneumonia,
      and 55 (22%) had meningitis. Mean age was 61 years, and mean Simplified Acute
      Physiology Score II was 50.4. One-half of the patients had bacteremia, and 84% of
      the cohort received mechanical ventilation. The hospital mortality rate was 31%.
      In the IPD group, the distribution of the FcgammaRIIa-R/H131 genotypes (H/H, 25%;
      H/R, 53%; R/R, 22%) was comparable with that in the white control group.
      Comparison of the FcgammaRIIa-R/R131 and the FcgammaRIIa-R/H131 + FcgammaRIIa
      H/H131 groups did not demonstrate any difference for age, Simplified Acute
      Physiology Score II, origin of sepsis, and other comorbid conditions. However,
      the variant FcgammaRIIa-R/R131 genotype was independently associated with
      decreased hospital mortality (OR, 0.251; 95% CI, 0.098-0.645; P = .004).
      CONCLUSIONS: In a well-defined population of patients with IPD, the frequency of
      the variant FcgammaRIIa-R131 does not differ from that of other critically ill
      patients. However, the FcgammaRIIa-R/R131 genotype was independently associated
      with increased survival, regardless of site of infection.

PMID- 22628492
TI  - Normal values and thresholds for the clinical interpretation of exhaled nitric
      oxide levels in the US general population: results from the National Health and
      Nutrition Examination Survey 2007-2010.
AB  - BACKGROUND: Elevated fractional excretion of exhaled nitric oxide (FENO) reflects
      airway inflammation, but few studies have established its normal values. This
      study aims to establish the normal values and thresholds for the clinical
      interpretation of FENO in the US general population. METHODS: Thirteen thousand
      two hundred seventy-five subjects aged 6 to 80 years sampled for the National
      Health and Nutrition Examination Survey (NHANES) 2007-2010 underwent interviews,
      physical examination, and FENO analysis at 50 mL/s using an online
      chemiluminescence device according to American Thoracic Society/European
      Respiratory Society guidelines. After excluding subjects with self-reported
      asthma and subjects with wheeze in the prior 12 months, prediction equations for
      the natural logarithm (ln) of FENO were constructed using age, sex, ethnicity,
      height, BMI, active/passive smoke exposure, and hay fever episodes as covariates.
      RESULTS: The fifth to 95th percentile values of FENO were 3.5 to 36.5 parts per
      billion (ppb) for children < 12 years of age and 3.5 to 39 ppb for subjects 12 to
      80 years of age. Using multiple linear regression, prediction equations explained
      only 10.3% to 15.7% of the variation in the general population. In the general
      population, 39% to 45% had ln(FENO) levels > 2 SD of the predicted means. When
      applied to the general population inclusive of subjects who reported asthma but
      who did not have attacks within the past year, nearly identical results were
      obtained. CONCLUSIONS: Assuming 95% of the healthy US general population had no
      clinically significant airway inflammation as assessed by FENO, values exceeding
      the 95th percentiles indicated abnormality and a high risk of airway
      inflammation. A large variation of normal FENO values existed in the general
      population, which was poorly predicted by multiple linear regression models.

PMID- 22628491
TI  - Multidetector CT scan for acute pulmonary embolism: embolic burden and clinical
      outcome.
AB  - BACKGROUND: In patients with acute pulmonary embolism (PE), the correlation
      between the embolic burden assessed by multidetector CT (MDCT) scan and clinical
      outcomes remains unclear. Patients with symptomatic acute PE diagnosed based on
      MDCT angiography were included in a multicenter study aimed at assessing the
      prognostic role of the embolic burden evaluated with MDCT scan. METHODS: Embolic
      burden was assessed as (1) localization of the emboli as central (saddle or at
      least one main pulmonary artery), lobar, or distal (segmental or subsegmental
      arteries) and (2) the obstruction index by the scoring system of Qanadli. The
      primary outcome was 30-day all-cause death or clinical deterioration. Predictors
      of all-cause death or clinical deterioration were identified by Cox regression
      statistics. RESULTS: Overall, 579 patients were included in the study; 60 (10.4%)
      died or had clinical deterioration at 30 days. Central localization of emboli was
      not associated with all-cause death or clinical deterioration (hazard ratio [HR],
      2.42; 95% CI, 0.77-7.59; P 5 .13). However, in 516 hemodynamically stable
      patients, central localization of emboli (HR, 8.3; 95% CI, 1.0-67; P 5 .047) was
      an independent predictor of all-cause death or clinical deterioration, whereas
      distal emboli were inversely associated with these outcome events (HR, 0.12; 95%
      CI, 0.015-0.97; P 5 .047). No correlation was found between obstruction index
      (evaluated in 448 patients) and all-cause death or clinical deterioration in the
      overall study population and in the hemodynamically stable patients. CONCLUSIONS:
      In hemodynamically stable patients with acute PE, central emboli are associated
      with an increased risk for all-cause death or clinical deterioration. This risk
      is low in patients with segmental or subsegmental PE.

PMID- 22628490
TI  - Oral treprostinil for the treatment of pulmonary arterial hypertension in
      patients on background endothelin receptor antagonist and/or phosphodiesterase
      type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial.
AB  - BACKGROUND: Infused and inhaled treprostinil are effective for treatment of
      pulmonary arterial hypertension (PAH), although their administration routes have
      limitations. This study assessed the efficacy and safety of bid oral sustained
      release treprostinil in the treatment of PAH with a concomitant endothelin
      receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor. METHODS: A
      16-week, multicenter, double-blind, placebo-controlled study was conducted in 350
      patients with PAH randomized to placebo or oral treprostinil. All patients were
      stable on background ERA, PDE-5 inhibitor, or both. Primary end point was Hodges
      Lehmann placebo-corrected median difference in change from baseline 6-min walk
      distance (6MWD) at week 16. Secondary end points included time to clinical
      worsening, change in World Health Organization functional class, Borg dyspnea
      score, and dyspnea fatigue index score. RESULTS: Thirty-nine patients (22%)
      receiving oral treprostinil and 24 patients (14%) receiving placebo discontinued
      the study. Placebo-corrected median difference in change from baseline 6MWD at
      week 16 was 11 m (P = .07). Improvements in dyspnea fatigue index score (P = .01)
      and combined 6MWD and Borg dyspnea score (P = .01) were observed with oral
      treprostinil vs placebo treatment. Patients who achieved a week-16 bid oral
      treprostinil dose of 1.25 to 3.25 mg and 3.5 to 16 mg experienced a greater
      change in 6MWD (18 m and 34 m, respectively) than patients who achieved a bid
      dose of < 1 mg or discontinued because of adverse events (4 m). CONCLUSIONS: The
      primary end point of improvement in 6MWD at week 16 did not achieve significance.
      This study enhanced understanding of oral treprostinil titration and dosing,
      which has set the stage for additional studies. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT00325442; URL: www.clinicaltrials.gov.

PMID- 22628493
TI  - Secondhand smoke exposure predicted COPD and other tobacco-related mortality in a
      17-year cohort study in China.
AB  - BACKGROUND: Prospective evidence on the association between secondhand smoke
      (SHS) and COPD and ischemic stroke is scarce. METHODS: We prospectively examined
      the relationship between SHS and major tobacco-related deaths, particularly COPD
      and stroke, in 910 Chinese (439 men, 471 women) who never smoked from a 17-year
      follow-up study in Xi'an, China. SHS exposure was defi ned as exposure to another
      person's tobacco smoke at home or in the workplace. RESULTS: At baseline among
      the 910 subjects, 44.2% were exposed to SHS at home, 52.9% in the workplace, and
      67.1% at home, work, or both. From March 1, 1994, to July 1, 2011, 249 (150
      men,99 women) died within 14,016 person-years. Those who were exposed to SHS had
      increased mortality due to coronary heart disease (adjusted relative risk [RR],
      2.15; 95% CI, 1.00-4.61), ischemic stroke (RR, 2.88; 95% CI, 1.10-7.55), lung
      cancer (RR, 2.00; 95% CI, 0.62-6.40), COPD (RR, 2.30;95% CI, 1.06-5.00), and all
      causes (RR, 1.72; 95% CI, 1.29-2.20), with significant dose-response
      relationships between cumulative SHS exposure at home and work and the increased
      risk of cause-specific and total mortality (P for linear trend ranged from .045
      to , .001). CONCLUSIONS: This study shows dose-response relationships between SHS
      and major tobacco-related mortality and provides new evidence to support
      causation for COPD and ischemic stroke.

PMID- 22628494
TI  - Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation
      phenotypes, and risk of colorectal adenoma in a multiethnic population.
AB  - OBJECTIVE: Heterocyclic amines (HAA) are animal carcinogens that are present in
      meat cooked at high temperature and in tobacco smoke. These compounds require
      activation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase-2 (NAT2)
      before they can damage DNA. This study tested the hypotheses that well-done meat
      and cigarette smoking increase the risk of adenoma, the precursor to most
      colorectal cancers, especially in individuals with rapid CYP1A2 and rapid NAT2
      activities. DESIGN: An endoscopy-based case-control study of adenoma was
      conducted among Caucasians, Japanese and native Hawaiians to test this
      hypothesis. The overall diet and consumption of well-done meat cooked by various
      high-temperature methods were assessed by interview in 1016 patients with a first
      adenoma and 1355 controls with a normal endoscopy. A caffeine test was used to
      assess CYP1A2 and NAT2 activities in 635 cases and 845 controls. Logistic
      regression was used to account for matching factors and potential confounders.
      RESULTS: Smoking was associated with an increased risk of adenoma. Weak non
      significant elevated OR were observed for the main effects of HAA intakes or NAT2
      activity. However, the combined effects of HAA intakes and NAT2 activity were
      statistically significant. Subjects in both the upper tertiles of NAT2 activity
      and HAA intake were at increased risk of adenoma compared with subjects in the
      lower tertiles of NAT2 activity and exposure (2-amino-3,4,8-dimethylimidazo[4,5
      f]quinoxaline intake OR 1.70, 95% CI I 1.06 to 2.75; 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline intake OR 1.91, 95% CI 1.16 to 3.16; and 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine intake OR 2.14, 95% CI 1.31 to
      3.49). CONCLUSION: The data suggest that rapid N-acetylators with high HAA intake
      may be at increased risk of adenoma.

PMID- 22628495
TI  - Draft genome sequence of an antibiotic-resistant Propionibacterium acnes strain,
      PRP-38, from the novel type IC cluster.
AB  - Propionibacterium acnes, a non-spore-forming, anaerobic gram-positive bacterium,
      is most notably recognized for its association with acne vulgaris (I. Kurokawa et
      al., Exp. Dermatol. 18:821-832, 2009). We now present the draft genome sequence
      of an antibiotic-resistant P. acnes strain, PRP-38, isolated from an acne patient
      in the United Kingdom and belonging to the novel type IC cluster.

PMID- 22628496
TI  - Draft genome sequence of Rubrivivax gelatinosus CBS.
AB  - Rubrivivax gelatinosus CBS, a purple nonsulfur photosynthetic bacterium, can grow
      photosynthetically using CO and N(2) as the sole carbon and nitrogen nutrients,
      respectively. R. gelatinosus CBS is of particular interest due to its ability to
      metabolize CO and yield H(2). We present the 5-Mb draft genome sequence of R.
      gelatinosus CBS with the goal of providing genetic insight into the metabolic
      properties of this bacterium.

PMID- 22628497
TI  - Genome sequence of cold-adapted Pseudomonas mandelii strain JR-1.
AB  - Pseudomonas mandelii is a cold-adapted bacterium that can grow at 4 degrees C but
      not at 37 degrees C. Here we report the draft genome sequence of P. mandelii
      strain JR-1.

PMID- 22628498
TI  - The genome of plant growth-promoting Bacillus amyloliquefaciens subsp. plantarum
      strain YAU B9601-Y2 contains a gene cluster for mersacidin synthesis.
AB  - The genome of rhizobacterium Bacillus amyloliquefaciens subsp. plantarum YAU
      B9601-Y2 was 4.24 Mb in size and harbored 3,991 coding sequences (CDS). Giant
      gene clusters were dedicated to nonribosomal synthesis of antimicrobial
      lipopeptides and polyketides. Remarkably, CAU B946 possessed a gene cluster
      involved in synthesis of mersacidin.

PMID- 22628499
TI  - Complete genome sequence of Francisella philomiragia ATCC 25017.
AB  - Francisella philomiragia is a saprophytic gammaproteobacterium found only
      occasionally in immunocompromised individuals and is the nearest neighbor to the
      causative agent of tularemia and category A select agent Francisella tularensis.
      To shed insight into the key genetic differences and the evolution of these two
      distinct lineages, we sequenced the first complete genome of F. philomiragia
      strain ATCC 25017, which was isolated as a free-living microorganism from water
      in Bear River Refuge, Utah.

PMID- 22628500
TI  - Genome sequence of proteorhodopsin-containing sea ice bacterium Glaciecola
      punicea ACAM 611T.
AB  - Here, we report the draft genome sequence of Antarctic sea ice bacterium
      Glaciecola punicea ACAM 611(T), the type species of the genus Glaciecola. A blue
      light-absorbing proteorhodopsin gene is present in the 3.08-Mb genome. This
      genome sequence can facilitate the study of the physiological metabolisms and
      ecological roles of sea ice bacteria.

PMID- 22628501
TI  - Complete genome sequence of Mycobacterium intracellulare clinical strain MOTT-64,
      belonging to the INT1 genotype.
AB  - Here, we report the complete genome sequence of the Mycobacterium intracellulare
      clinical strain MOTT-64, previously grouped into the INT1 genotype among five
      genotypes of M. intracellulare. This genome sequence will serve as a valuable
      reference for understanding the disparity in the virulence and epidemiologic
      traits among M. intracellulare genotypes.

PMID- 22628502
TI  - The draft genome sequence of Corynebacterium diphtheriae bv. mitis NCTC 3529
      reveals significant diversity between the primary disease-causing biovars.
AB  - We report the draft genome of the human pathogen Corynebacterium diphtheriae bv.
      mitis NCTC 3529. This is the first C. diphtheriae bv. mitis strain to be
      sequenced and reveals significant differences from the other primary biovar, C.
      diphtheriae bv. gravis.

PMID- 22628503
TI  - Complete genome sequence of Riemerella anatipestifer reference strain.
AB  - Riemerella anatipestifer is an infectious pathogen causing serositis in ducks. We
      had the genome of the R. anatipestifer reference strain ATCC 11845 sequenced. The
      completed draft genome consists of one circular chromosome with 2,164,087 bp.
      There are 2,101 genes in the draft, and its GC content is 35.01%.

PMID- 22628504
TI  - Genome sequences of two plant growth-promoting fluorescent Pseudomonas strains,
      R62 and R81.
AB  - Plant growth-promoting rhizobacterial (PGPR) strains R62 and R81 have previously
      been isolated and characterized as part of the Indo-Swiss Collaboration in
      Biotechnology. Here we present the draft genome sequences of these two PGPR
      strains, with the aim of unraveling the mechanisms behind their ability to
      promote wheat growth.

PMID- 22628505
TI  - Genome sequences of five Salmonella enterica serovar Heidelberg isolates
      associated with a 2011 multistate outbreak in the United States.
AB  - Salmonella enterica serovar Heidelberg has caused numerous outbreaks in humans.
      Here, we report draft genomes of five isolates of serovar Heidelberg associated
      with the recent (2011) multistate outbreak linked to ground turkey in the United
      States. Isolates 2011K-1110 and 2011K-1132 were recovered from humans, while
      isolates 2011K-1138, 2011K-1224, and 2011K-1225 were recovered from ground
      turkey. Whole-genome sequence analysis of these isolates provides a tool for
      studying the short-term evolution of these epidemic clones.

PMID- 22628507
TI  - Genome sequence of the Mycobacterium abscessus strain M93.
AB  - Mycobacterium abscessus is a rapid-growing species of nontuberculous mycobacteria
      that is frequently associated with opportunistic infections in humans. We report
      herein the draft genome sequence of M. abscessus strain M93.

PMID- 22628506
TI  - Genome sequences of Pseudomonas fragi strains A22 and B25.
AB  - Pseudomonas fragi A22 is a novel isolate that produces bead-like particles (A22B)
      in its cell wall. To explore the genetic basis for the formation of A22B, P.
      fragi A22 and the type strain of the species, P. fragi B25, were subjected to
      genome sequence analysis. Here, we report the draft genome sequences and
      automatic annotation of both strains. These data offer a solid base for related
      studies of P. fragi, including comparative genomics, proteomics, and gene mining.

PMID- 22628508
TI  - Draft genome sequence for Microbacterium laevaniformans strain OR221, a bacterium
      tolerant to metals, nitrate, and low pH.
AB  - Microbacterium laevaniformans strain OR221 was isolated from subsurface sediments
      obtained from the Field Research Center (FRC) in Oak Ridge, TN. It was
      characterized as a bacterium tolerant to heavy metals, such as uranium, nickel,
      cobalt, and cadmium, as well as nitrate and low pH. We present its draft genome
      sequence.

PMID- 22628509
TI  - Whole-genome sequence of Klebsiella pneumonia strain LCT-KP214.
AB  - Klebsiella pneumoniae is a gram-negative, nonmotile, encapsulated, lactose
      fermenting, facultative anaerobic, rod-shaped bacterium found in the normal flora
      of the mouth, skin, and intestines. Here we present the fine-draft genome
      sequence of K. pneumoniae strain LCT-KP214, which originated from K. pneumoniae
      strain CGMCC 1.1736.

PMID- 22628510
TI  - Complete genome sequence of Mycobacterium xenopi type strain RIVM700367.
AB  - Mycobacterium xenopi is a slow-growing, thermophilic, water-related Mycobacterium
      species. Like other nontuberculous mycobacteria, M. xenopi more commonly infects
      humans with altered immune function, such as chronic obstructive pulmonary
      disease patients. It is considered clinically relevant in a significant
      proportion of the patients from whom it is isolated. We report here the whole
      genome sequence of M. xenopi type strain RIVM700367.

PMID- 22628511
TI  - Complete genome sequence of Mycobacterium phlei type strain RIVM601174.
AB  - Mycobacterium phlei is a rapidly growing nontuberculous Mycobacterium species
      that is typically nonpathogenic, with few reported cases of human disease. Here
      we report the whole genome sequence of M. phlei type strain RIVM601174.

PMID- 22628512
TI  - Genome sequence of the nitroaromatic compound-degrading Bacterium Burkholderia
      sp. strain SJ98.
AB  - We report the 7.85-Mb genome sequence of Burkholderia sp. strain SJ98, isolated
      from agricultural fields of Assam, India. The draft genome of this strain will be
      helpful in studying the genetic pathways involved in the degradation of aromatic
      compounds.

PMID- 22628513
TI  - Genome sequence of Diplorickettsia massiliensis, an emerging Ixodes ricinus
      associated human pathogen.
AB  - Diplorickettsia massiliensis is a gammaproteobacterium in the order Legionellales
      and an agent of tick-borne infection. We sequenced the genome from strain 20B,
      isolated from an Ixodes ricinus tick. The genome consists of a 1,727,973-bp
      chromosome but no plasmid and includes 2,269 protein-coding genes and 42 RNA
      genes, including 3 rRNA genes.

PMID- 22628514
TI  - Genome sequence of Rickettsia conorii subsp. indica, the agent of Indian tick
      typhus.
AB  - Rickettsia conorii subsp. indica is the agent of Indian tick typhus. The present
      study reports the draft genome of Rickettsia conorii subsp. indica strain ITTR
      (ATCC VR-597).

PMID- 22628515
TI  - Draft genome sequences for Clostridium thermocellum wild-type strain YS and
      derived cellulose adhesion-defective mutant strain AD2.
AB  - Clostridium thermocellum wild-type strain YS is an anaerobic, thermophilic,
      cellulolytic bacterium capable of directly converting cellulosic substrates into
      ethanol. Strain YS and a derived cellulose adhesion-defective mutant strain, AD2,
      played pivotal roles in describing the original cellulosome concept. We present
      their draft genome sequences.

PMID- 22628516
TI  - Complete genome sequence of Pasteurella multocida HN06, a toxigenic strain of
      serogroup D.
AB  - Pasteurella multocida is an important etiological agent that can cause many
      economically important diseases in a wide range of mammals and birds. Here, we
      report the complete genome sequence of P. multocida HN06, a toxigenic serogroup D
      strain isolated from a diseased pig in China.

PMID- 22628517
TI  - Complete genome sequence of Streptococcus pneumoniae strain ST556, a multidrug
      resistant isolate from an otitis media patient.
AB  - Streptococcus pneumoniae is a major pathogen causing bacterial infection in the
      middle ear of humans. We previously used S. pneumoniae strain ST556, a low
      passage 19F isolate from an otitis media patient, to perform a whole-genome
      screen for ear infection-associated genes in a chinchilla model. This report
      presents the complete genome sequence of ST556. The genome sequence will provide
      information complementary to the experimental data from our genetic study of this
      strain.

PMID- 22628518
TI  - Magnetic versus manual catheter navigation for ablation of free wall accessory
      pathways in children.
AB  - BACKGROUND: Transcatheter ablation of accessory pathway (AP)-mediated tachycardia
      is routinely performed in children. Little data exist regarding the use of
      magnetic navigation (MN) and its potential benefits for ablation of AP-mediated
      tachycardia in this population. METHODS AND RESULTS: We performed a retrospective
      review of prospectively gathered data in children undergoing radiofrequency
      ablation at our institution since the installation of MN (Stereotaxis Inc, St.
      Louis, MO) in March 2009. The efficacy and safety between an MN-guided approach
      and standard manual techniques for mapping and ablation of AP-mediated
      tachycardia were compared. During the 26-month study period, 145 patients
      underwent radiofrequency ablation for AP-mediated tachycardia. Seventy-three
      patients were ablated with MN and 72 with a standard manual approach. There were
      no significant differences in demographic factors between the 2 groups with a
      mean cohort age of 13.1+/-4.0 years. Acute success rates were equivalent with 68
      of 73 (93.2%) patients in the MN group being successfully ablated versus 68 of 72
      (94.4%) patients in the manual group (P=0.889). During a median follow-up of 21.4
      months, there were no recurrences in the MN group and 2 recurrences in the manual
      group (P=0.388). There were no differences in time to effect, number of lesions
      delivered, or average ablation power. There was also no difference in total
      procedure time, but fluoroscopy time was significantly reduced in the MN group at
      14.0 (interquartile range, 3.8-23.9) minutes compared with the manual group at
      28.1 (interquartile range, 15.3-47.3) minutes (P<0.001). There were no
      complications in either group. CONCLUSIONS: MN is a safe and effective approach
      to ablate AP-mediated tachycardia in children.

PMID- 22628519
TI  - RAxML-Light: a tool for computing terabyte phylogenies.
AB  - MOTIVATION: Due to advances in molecular sequencing and the increasingly rapid
      collection of molecular data, the field of phyloinformatics is transforming into
      a computational science. Therefore, new tools are required that can be deployed
      in supercomputing environments and that scale to hundreds or thousands of cores.
      RESULTS: We describe RAxML-Light, a tool for large-scale phylogenetic inference
      on supercomputers under maximum likelihood. It implements a light-weight
      checkpointing mechanism, deploys 128-bit (SSE3) and 256-bit (AVX) vector
      intrinsics, offers two orthogonal memory saving techniques and provides a fine
      grain production-level message passing interface parallelization of the
      likelihood function. To demonstrate scalability and robustness of the code, we
      inferred a phylogeny on a simulated DNA alignment (1481 taxa, 20 000 000 bp)
      using 672 cores. This dataset requires one terabyte of RAM to compute the
      likelihood score on a single tree. CODE AVAILABILITY:
      https://github.com/stamatak/RAxML-Light-1.0.5 DATA AVAILABILITY:
      http://www.exelixis-lab.org/onLineMaterial.tar.bz2 CONTACT:
      alexandros.stamatakis@h-its.org SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 22628520
TI  - Application of survival analysis methodology to the quantitative analysis of LC
      MS proteomics data.
AB  - MOTIVATION: Protein abundance in quantitative proteomics is often based on
      observed spectral features derived from liquid chromatography mass spectrometry
      (LC-MS) or LC-MS/MS experiments. Peak intensities are largely non-normal in
      distribution. Furthermore, LC-MS-based proteomics data frequently have large
      proportions of missing peak intensities due to censoring mechanisms on low
      abundance spectral features. Recognizing that the observed peak intensities
      detected with the LC-MS method are all positive, skewed and often left-censored,
      we propose using survival methodology to carry out differential expression
      analysis of proteins. Various standard statistical techniques including non
      parametric tests such as the Kolmogorov-Smirnov and Wilcoxon-Mann-Whitney rank
      sum tests, and the parametric survival model and accelerated failure time-model
      with log-normal, log-logistic and Weibull distributions were used to detect any
      differentially expressed proteins. The statistical operating characteristics of
      each method are explored using both real and simulated datasets. RESULTS:
      Survival methods generally have greater statistical power than standard
      differential expression methods when the proportion of missing protein level data
      is 5% or more. In particular, the AFT models we consider consistently achieve
      greater statistical power than standard testing procedures, with the discrepancy
      widening with increasing missingness in the proportions. AVAILABILITY: The
      testing procedures discussed in this article can all be performed using readily
      available software such as R. The R codes are provided as supplemental materials.
      CONTACT: ctekwe@stat.tamu.edu.

PMID- 22628521
TI  - The UEA sRNA workbench: a suite of tools for analysing and visualizing next
      generation sequencing microRNA and small RNA datasets.
AB  - SUMMARY: RNA silencing is a complex, highly conserved mechanism mediated by small
      RNAs (sRNAs), such as microRNAs (miRNAs), that is known to be involved in a
      diverse set of biological functions including development, pathogen control,
      genome maintenance and response to environmental change. Advances in next
      generation sequencing technologies are producing increasingly large numbers of
      sRNA reads per sample at a fraction of the cost of previous methods. However,
      many bioinformatics tools do not scale accordingly, are cumbersome, or require
      extensive support from bioinformatics experts. Therefore, researchers need user
      friendly, robust tools, capable of not only processing large sRNA datasets in a
      reasonable time frame but also presenting the results in an intuitive fashion and
      visualizing sRNA genomic features. Herein, we present the UEA sRNA workbench, a
      suite of tools that is a successor to the web-based UEA sRNA Toolkit, but in
      downloadable format and with several enhanced and additional features.
      AVAILABILITY: The program and help pages are available at http://srna
      workbench.cmp.uea.ac.uk. CONTACT: vincent.moulton@cmp.uea.ac.uk.

PMID- 22628522
TI  - Multi-scale computational modeling of developmental biology.
AB  - MOTIVATION: Normal development of multicellular organisms is regulated by a
      highly complex process in which a set of precursor cells proliferate,
      differentiate and move, forming over time a functioning tissue. To handle their
      complexity, developmental systems can be studied over distinct scales. The
      dynamics of each scale is determined by the collective activity of entities at
      the scale below it. RESULTS: I describe a multi-scale computational approach for
      modeling developmental systems and detail the methodology through a synthetic
      example of a developmental system that retains key features of real developmental
      systems. I discuss the simulation of the system as it emerges from cross-scale
      and intra-scale interactions and describe how an in silico study can be carried
      out by modifying these interactions in a way that mimics in vivo experiments. I
      highlight biological features of the results through a comparison with findings
      in Caenorhabditis elegans germline development and finally discuss about the
      applications of the approach in real developmental systems and propose future
      extensions. AVAILABILITY AND IMPLEMENTATION: The source code of the model of the
      synthetic developmental system can be found in
      www.wisdom.weizmann.ac.il/~yaki/MultiScaleModel. CONTACT: yaki.setty@gmail.com
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22628523
TI  - DoGSiteScorer: a web server for automatic binding site prediction, analysis and
      druggability assessment.
AB  - MOTIVATION: Many drug discovery projects fail because the underlying target is
      finally found to be undruggable. Progress in structure elucidation of proteins
      now opens up a route to automatic structure-based target assessment.
      DoGSiteScorer is a newly developed automatic tool combining pocket prediction,
      characterization and druggability estimation and is now available through a web
      server. AVAILABILITY: The DoGSiteScorer web server is freely available for
      academic use at http://dogsite.zbh.uni-hamburg.de CONTACT: rarey@zbh.uni
      hamburg.de.

PMID- 22628524
TI  - Marker2sequence, mine your QTL regions for candidate genes.
AB  - Marker2sequence (M2S) aims at mining quantitative trait loci (QTLs) for candidate
      genes. For each gene, within the QTL region, M2S uses data integration technology
      to integrate putative gene function with associated gene ontology terms,
      proteins, pathways and literature. As a typical QTL region easily contains
      several hundreds of genes, this gene list can then be further filtered using a
      keyword-based query on the aggregated annotations. M2S will help breeders to
      identify potential candidate genes for their traits of interest. AVAILABILITY:
      Marker2sequence is freely accessible at
      http://www.plantbreeding.wur.nl/BreeDB/marker2seq/. The source code can be
      obtained at https://github.com/PBR/Marker2Sequence. CONTACT:
      richard.finkers@wur.nl

PMID- 22628525
TI  - An analysis of the radiation field characteristics for extremity dose assessment
      during maintenance periods at nuclear power plants in Korea.
AB  - Workers who maintain the water chambers of steam generators during maintenance
      periods in nuclear power plants (NPPs) have a higher likelihood of high radiation
      exposure, even if they are exposed for a short period of time. In particular, it
      is expected that the hands of workers would receive the highest radiation
      exposure as a consequence of hand contact with radioactive materials. In this
      study, a characteristic analysis of inhomogeneous radiation fields for contact
      operations was conducted using thermoluminescent dosemeters for the whole body
      and extremities during maintenance periods at Korean NPPs. It was observed that
      inhomogeneous radiation fields for contact operations at NPPs were dominated by
      high-energy photons.

PMID- 22628526
TI  - An evaluation of a manganese bath system having a new geometry through MCNP
      modelling.
AB  - In this study, an approximate symmetric cylindrical manganese bath system with
      equal diameter and height was appraised using a Monte Carlo simulation. For nine
      sizes of the tank filled with MnSO(4).H(2)O solution of three different
      concentrations, the necessary correction factors involved in the absolute
      measurement of neutron emission rate were determined by a detailed modelling of
      the MCNP4C code with the ENDF/B-VII.0 neutron cross section data library. The
      results obtained were also used to determine the optimum dimensions of the bath
      for each concentration of solution in the calibration of (241)Am-Be and (252)Cf
      sources. Also, the amount of gamma radiation produced as a result of (n,gamma)
      the reaction with the nuclei of the manganese sulphate solution that escaped from
      the boundary of each tank was evaluated. This gamma can be important for the
      background in NaI(Tl) detectors and issues concerned with radiation protection.

PMID- 22628527
TI  - A novel device for automatic withdrawal and accurate calibration of 99m
      technetium radiopharmaceuticals to minimise radiation exposure to nuclear
      medicine staff and patient.
AB  - A Joint Automatic Dispenser Equipment (JADE) has been designed and fabricated for
      automatic withdrawal and calibration of radiopharmaceutical materials. The
      thermoluminescent dosemeter procedures have shown a reduction in dose to the
      technician's hand with this novel dose dispenser system JADE when compared with
      the manual withdrawal of (99m)Tc. This system helps to increase the precision of
      calibration and to minimise the radiation dose to the hands and body of the
      workers. This paper describes the structure of this device, its function and user
      friendliness, and its efficacy. The efficacy of this device was determined by
      measuring the radiation dose delivered to the hands of the nuclear medicine
      laboratory technician. The user-friendliness of JADE has been examined. The
      automatic withdrawal and calibration offered by this system reduces the dose to
      the technician's hand to a level below the maximum permissible dose stipulated by
      the international protocols. This research will serve as a backbone for future
      study about the safe use of ionising radiation in medicine.

PMID- 22628528
TI  - Reassessment of 239Pu on planchets from human urine samples at ultra-trace levels
      using Aridus-ICPSFMS and AMS.
AB  - New analytical methods developed at the facilities here, based on two ultra
      sensitive mass spectrometry (MS) techniques, inductively coupled plasma sector
      field mass spectrometer with a desolvator system (Aridus-ICP-SFMS) and
      accelerator MS (AMS), have been applied in this work for the reassessment of
      (239)Pu in alpha spectrometry (AS) planchets corresponding to spiked human urine
      samples. The obtained (239)Pu minimum detectable activities (MDAs) values by
      Aridus-ICP-SFMS and AMS were 3 fg (~6.92 uBq) and 0.4 fg (~0.92 uBq),
      respectively, per sample, which are much better than those attainable by AS [50
      fg (~115.3 uBq) of (239)Pu per sample, approximately]. Therefore, it is
      demonstrated that the MS techniques employed in this work are very powerful tools
      for internal dosimetry studies in human urine samples, giving excellent results
      when the reassessment of AS planchets is needed (samples with a Pu concentration
      below or at the MDA levels measurable by AS). This work is the continuation of an
      article published in J. Anal. At. Spectrom. 25 (1410-1415) 2010.

PMID- 22628529
TI  - Chronic administration of oral vasopressin type 2 receptor antagonist tolvaptan
      exerts both myocardial and renal protective effects in rats with hypertensive
      heart failure.
AB  - BACKGROUND: Although recent clinical trials have demonstrated the efficacy of the
      oral vasopressin (AVP) type 2 receptor (V2R) antagonist tolvaptan, its long-term
      effects on the myocardium and kidney in heart failure (HF) are not clear. We
      examined the chronic effects of tolvaptan administration on both the myocardium
      and kidney in a rat hypertensive HF model. METHODS AND RESULTS: Not only
      circulating AVP level but also myocardial AVP and V1a receptor (V1aR)
      expressions, renal V1aR, and V2R expressions were significantly upregulated
      during the transition to HF. The animals were chronically treated with low-dose
      or high-dose (HD) tolvaptan or vehicle from the left ventricular (LV)
      hypertrophic stage. Chronic tolvaptan treatment persistently increased urine
      volume but did not affect blood pressure. In the HD group, the animal survival
      significantly improved (log-rank test, P<0.01). At the HF stage, the progression
      of LV dysfunction was prevented and lung congestion was suppressed. Activation of
      atrial natriuretic peptide, endothelin-1, AVP, and V1aR mRNA levels were
      significantly suppressed in the LV myocardium. Meanwhile, renal histopathologic
      damage was ameliorated and renal function was improved in the HD group at the HF
      stage. Concomitantly, not only activation of aquaporin-2 but also those of V2R,
      V1aR, renin, and endothelin-1 in the kidney were significantly suppressed (all
      P<0.05). CONCLUSIONS: These results indicate that chronic tolvaptan treatment has
      beneficial effects by preventing not only the progression of LV dysfunction but
      also that of renal injury in hypertensive rats with HF. The underlying mechanism
      may be related to the suppression of myocardial and renal neurohumoral
      activation.

PMID- 22628531
TI  - Origin and spread of photosynthesis based upon conserved sequence features in key
      bacteriochlorophyll biosynthesis proteins.
AB  - The origin of photosynthesis and how this capability has spread to other
      bacterial phyla remain important unresolved questions. I describe here a number
      of conserved signature indels (CSIs) in key proteins involved in
      bacteriochlorophyll (Bchl) biosynthesis that provide important insights in these
      regards. The proteins BchL and BchX, which are essential for Bchl biosynthesis,
      are derived by gene duplication in a common ancestor of all phototrophs. More
      ancient gene duplication gave rise to the BchX-BchL proteins and the NifH protein
      of the nitrogenase complex. The sequence alignment of NifH-BchX-BchL proteins
      contain two CSIs that are uniquely shared by all NifH and BchX homologs, but not
      by any BchL homologs. These CSIs and phylogenetic analysis of NifH-BchX-BchL
      protein sequences strongly suggest that the BchX homologs are ancestral to BchL
      and that the Bchl-based anoxygenic photosynthesis originated prior to the
      chlorophyll (Chl)-based photosynthesis in cyanobacteria. Another CSI in the BchX
      BchL sequence alignment that is uniquely shared by all BchX homologs and the BchL
      sequences from Heliobacteriaceae, but absent in all other BchL homologs, suggests
      that the BchL homologs from Heliobacteriaceae are primitive in comparison to all
      other photosynthetic lineages. Several other identified CSIs in the BchN homologs
      are commonly shared by all proteobacterial homologs and a clade consisting of the
      marine unicellular Cyanobacteria (Clade C). These CSIs in conjunction with the
      results of phylogenetic analyses and pair-wise sequence similarity on the BchL,
      BchN, and BchB proteins, where the homologs from Clade C Cyanobacteria and
      Proteobacteria exhibited close relationship, provide strong evidence that these
      two groups have incurred lateral gene transfers. Additionally, phylogenetic
      analyses and several CSIs in the BchL-N-B proteins that are uniquely shared by
      all Chlorobi and Chloroflexi homologs provide evidence that the genes for these
      proteins have also been laterally transferred between these groups. Other results
      and observations reported here indicate that the genes for the BchL-N-B proteins
      in Proteobacteria are derived from the Clade C Cyanobacteria, whereas those in
      Chlorobi were acquired from Chloroflexus or related bacteria by means of LGTs.
      Some implications of these observations regarding the origin and spread of
      photosynthesis are discussed.

PMID- 22628530
TI  - Circulating matrix metalloproteinases in adolescents with hypertrophic
      cardiomyopathy and ventricular arrhythmia.
AB  - BACKGROUND: Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy
      (HCM) and a risk factor for ventricular arrhythmia. Fibrosis can be reflected in
      circulating matrix remodeling protein concentrations. We explored differences in
      circulating markers of extracellular matrix turnover between young HCM patients
      with versus without history of serious arrhythmia. METHODS AND RESULTS: Using
      multiplexed and single ELISA, matrix metalloproteinases (MMPs) 1, 2, 3, and 9;
      tissue inhibitor of metalloproteinases (TIMPs) 1, 2, and 4; and collagen I
      carboxyterminal peptide (CICP) were measured in plasma from 45 young HCM patients
      (80% male patients; median age, 17 years [interquartile range, 15-20]).
      Participants were grouped into serious ventricular arrhythmia history (VA) versus
      no ventricular arrhythmia history (NoVA). Differences in MMPs between groups were
      examined nonparametrically. Relationships between MMPs and ventricular arrhythmia
      were assessed with linear regression, adjusted for interventricular septal
      thickness, family history of sudden death, abnormal exercise blood pressure, and
      implantable cardioverter-defibrillator (ICD). In post hoc sensitivity analysis,
      age was substituted for ICD. The 14 VA patients were older than 31 NoVA patients
      (median, 19 versus 17 years; P=0.03). All 14 VA and 12 NoVA patients had an ICD.
      MMP3 concentration was significantly higher in the VA group (VA median, 12.9
      MUg/mL [interquartile range, 5.7-16.7 MUg/mL] versus NoVA, 5.8 MUg/mL
      [interquartile range, 3.7-10.0 MUg/mL]; P=0.01). On multivariable analysis, VA
      was independently associated with increasing MMP3 (standardized beta, 0.37;
      P=0.01). Post hoc adjustment for age attenuated this association. CONCLUSIONS:
      Circulating MMP3 may be a marker of ventricular arrhythmia in adolescent patients
      with HCM. Because of our role as pediatric providers, we cannot exclude age
      related confounding.

PMID- 22628532
TI  - In silico characterization and molecular evolutionary analysis of a novel
      superfamily of fungal effector proteins.
AB  - Most fungal plant pathogens secrete effector proteins during pathogenesis to
      manipulate their host's defense and promote disease. These are so highly diverse
      in sequence and distribution, they are essentially considered as species
      specific. However, we have recently shown the presence of homologous effectors in
      fungal species of the Dothideomycetes class. One such example is Ecp2, an
      effector originally described in the tomato pathogen Cladosporium fulvum but
      later detected in the plant pathogenic fungi Mycosphaerella fijiensis and
      Mycosphaerella graminicola as well. Here, using in silico sequence-similarity
      searches against a database of 135 fungal genomes and GenBank, we extend our
      queries for homologs of Ecp2 to the fungal kingdom and beyond, and further study
      their history of diversification. Our analyses show that Ecp2 homologs are
      members of an ancient and widely distributed superfamily of putative fungal
      effectors, which we term Hce2 for Homologs of C. fulvum Ecp2. Molecular
      evolutionary analyses show that the superfamily originated and diversified within
      the fungal kingdom, experiencing multiple lineage-specific expansions and losses
      that are consistent with the birth-and-death model of gene family evolution.
      Newly formed paralogs appear to be subject to diversification early after gene
      duplication events, whereas at later stages purifying selection acts to preserve
      diversity and the newly evolved putative functions. Some members of the Hce2
      superfamily are fused to fungal Glycoside Hydrolase family 18 chitinases that
      show high similarity to the Zymocin killer toxin from the dairy yeast
      Kluyveromyces lactis, suggesting an analogous role in antagonistic interactions.
      The observed high rates of gene duplication and loss in the Hce2 superfamily,
      combined with diversification in both sequence and possibly functions within and
      between species, suggest that Hce2s are involved in adaptation to stresses and
      new ecological niches. Such findings address the need to rationalize effector
      biology and evolution beyond the perspective of solely host-microbe interactions.

PMID- 22628534
TI  - Genetic adaptation of the hypoxia-inducible factor pathway to oxygen pressure
      among eurasian human populations.
AB  - Research into the mechanisms of human adaptation to the hypoxic environment of
      high altitude is of great interest to the fields of human physiology and clinical
      medicine. Recently, the gene EGLN1, from the hypoxia-inducible factor (HIF)
      pathway, was identified as being involved in the hypoxic adaptation of highland
      Andeans and Tibetans. Both highland Andeans and Tibetans have adapted to an
      extremely hypoxic habitat and less attention has been paid to populations living
      in normoxic conditions at sea level and mild-hypoxic environments of moderate
      altitude, thus, whether a common adaptive mechanism exists in response to
      quantitative variations of environmental oxygen pressure over a wide range of
      residing altitudes is unknown. Here, we first performed a genome-wide association
      study of 35 populations from the Human Genome Diversity-CEPH Panel who dwell at
      sea level to moderate altitude in Eurasia (N = 691; 0-2,500 m) to identify the
      genetic adaptation profile of normoxic and mild-hypoxic inhabitants. In addition,
      we systematically compared the results from the present study to six previously
      published genome-wide scans of highland Andeans and Tibetans to identify shared
      adaptive signals in response to quantitative variations of oxygen pressure. For
      normoxic and mild-hypoxic populations, the strongest adaptive signal came from
      the mu opioid receptor-encoding gene (OPRM1, 2.54 * 10(-9)), which has been
      implicated in the stimulation of respiration, while in the systematic survey the
      EGLN1-DISC1 locus was identified in all studies. A replication study performed
      with highland Tibetans (N = 733) and sea level Han Chinese (N = 748) confirmed
      the association between altitude and SNP allele frequencies in OPRM1 (in Tibetans
      only, P < 0.01) and in EGLN1-DISC1 (in Tibetans and Han Chinese, P < 0.01). Taken
      together, identification of the OPRM1 gene suggests that cardiopulmonary
      adaptation mechanisms are important and should be a focus in future studies of
      hypoxia adaptation. Furthermore, the identification of the EGLN1 gene from the
      HIF pathway suggests a common adaptive mechanism for Eurasian human populations
      residing at different altitudes with different oxygen pressures.

PMID- 22628533
TI  - Evolution of saxitoxin synthesis in cyanobacteria and dinoflagellates.
AB  - Dinoflagellates produce a variety of toxic secondary metabolites that have a
      significant impact on marine ecosystems and fisheries. Saxitoxin (STX), the cause
      of paralytic shellfish poisoning, is produced by three marine dinoflagellate
      genera and is also made by some freshwater cyanobacteria. Genes involved in STX
      synthesis have been identified in cyanobacteria but are yet to be reported in the
      massive genomes of dinoflagellates. We have assembled comprehensive transcriptome
      data sets for several STX-producing dinoflagellates and a related non-toxic
      species and have identified 265 putative homologs of 13 cyanobacterial STX
      synthesis genes, including all of the genes directly involved in toxin synthesis.
      Putative homologs of four proteins group closely in phylogenies with
      cyanobacteria and are likely the functional homologs of sxtA, sxtG, and sxtB in
      dinoflagellates. However, the phylogenies do not support the transfer of these
      genes directly between toxic cyanobacteria and dinoflagellates. SxtA is split
      into two proteins in the dinoflagellates corresponding to the N-terminal portion
      containing the methyltransferase and acyl carrier protein domains and a C
      terminal portion with the aminotransferase domain. Homologs of sxtB and N
      terminal sxtA are present in non-toxic strains, suggesting their functions may
      not be limited to saxitoxin production. Only homologs of the C-terminus of sxtA
      and sxtG were found exclusively in toxic strains. A more thorough survey of STX+
      dinoflagellates will be needed to determine if these two genes may be specific to
      SXT production in dinoflagellates. The A. tamarense transcriptome does not
      contain homologs for the remaining STX genes. Nevertheless, we identified
      candidate genes with similar predicted biochemical activities that account for
      the missing functions. These results suggest that the STX synthesis pathway was
      likely assembled independently in the distantly related cyanobacteria and
      dinoflagellates, although using some evolutionarily related proteins. The
      biological role of STX is not well understood in either cyanobacteria or
      dinoflagellates. However, STX production in these two ecologically distinct
      groups of organisms suggests that this toxin confers a benefit to producers that
      we do not yet fully understand.

PMID- 22628535
TI  - 3-T Diffusion tensor imaging of the optic nerve in subjects with glaucoma:
      correlation with GDx-VCC, HRT-III and Stratus optical coherence tomography
      findings.
AB  - OBJECTIVES: To correlate diffusion-tensor imaging (DTI) of the optic nerve with
      morphological indices obtained by scanning laser polarimetry (GDx-VCC); confocal
      scanning laser ophthalmoscopy (Heidelberg III retinal tomograph; HRT-III) and
      optical coherence tomography (Stratus OCT). METHODS: Thirty-six subjects (12 with
      no eye disease and 24 with perimetrically diagnosed glaucoma) were examined. One
      eye for each participant was studied with 3-Tesla DTI (with automatic generation
      of mean diffusivity (MD) and fractional anisotropy (FA) values); GDx-VCC, HRT-III
      and OCT. Single and multiple regression analyses of all variables studied were
      performed. RESULTS: MD displayed the strongest correlation with linear cup/disc
      ratio (LCDR) from HTR-III (r=0.662), retinal nerve fibre layer (RNFL) thickness
      (avThickn) from OCT (r=-0.644), and nerve fibre index (NFI) from GDx (r=0.642);
      FA was strongly correlated with the LCDR (r=-0.499). In multiple regression
      analyses, MD correlated with LCDR (p=0.02) when all variables were considered;
      with avThickn (p<0.01) (analysis of all RNFL parameters); with NFI (p<0.01)
      (analysis of all GDx parameters); with avThickn (p<0.01) (analysis of OCT
      parameters); with LCDR (p=0.01) (analysis of HRT-III morphometric parameters) and
      with linear discriminant function (RB) (p=0.02) (analysis of HRT-III indices). As
      for FA, it correlated with avThickn (p=0.02) when we analysed the OCT parameters
      and with RB (p=0.01) (analysis of HRT-III indices). CONCLUSIONS: DTI parameters
      of the axonal architecture of the optic nerve show good correlation with
      morphological features of the optic nerve head and RNFL documented with GDx-VCC,
      HRT-III and OCT.

PMID- 22628536
TI  - Homocysteine induces oxidative stress in young adult central retinal vein
      occlusion.
AB  - OBJECTIVES: High levels of plasma homocysteine have been reported to be toxic to
      the vascular endothelium, thereby creating an environment of hypercoagulability
      and occlusion. Elevated homocysteine has been reported as a risk factor for young
      adult central retinal vein occlusion (CRVO) cases. This study aimed to see if
      oxidative stress is an independent risk factor or is homocysteine dependent.
      METHODS: 23 young adult CRVO patients and 54 age and sex-matched controls were
      included in the study. Oxidative stress markers thiobarbituric acid-reacting
      substance (TBARS), superoxide dismutase (SOD), total thiols, glutathione
      peroxidase and total antioxidant capacity (TAC) were estimated. The effect of
      homocysteine (25-200 MUM) on cultured bovine retinal endothelial cells (BREC) on
      oxidative stress parameter TBARS was measured. RESULTS: There was a significant
      increase in the plasma TBARS in CRVO cases compared with controls (p=0.000). SOD
      and TAC were significantly lower in CRVO cases than controls (p=0.000, p=0.022).
      There was a significant negative correlation between TAC and TBARS (p=0.00) and a
      significant positive correlation between homocysteine and TBARS (p=0.029).
      Nominal regression analysis showed that TAC and homocysteine influence TBARS
      significantly. The in-vitro study in BREC cells revealed that homocysteine
      increased the TBARS dose and time dependently. CONCLUSION: TBARS and homocysteine
      are known to be independent risk factors for CRVO. TBARS can be influenced by
      both homocysteine and TAC, thereby contributing to the aetiopathology of CRVO by
      increasing oxidative stress.

PMID- 22628537
TI  - Baerveldt shunts in the treatment of glaucoma secondary to anterior uveal
      melanoma and proton beam radiotherapy.
AB  - INTRODUCTION: Melanoma of the iris and ciliary body may be associated with
      secondary glaucoma. Treatment with proton beam radiotherapy (PBRT) to the
      anterior segment can also elevate intraocular pressure (IOP), resulting in
      uncontrolled glaucoma, often requiring enucleation. This is the first prospective
      study of Baerveldt aqueous shunts in irradiated eyes with anterior uveal melanoma
      (AUM; affecting the iris or ciliary body). METHODS: Thirty-one eyes with
      uncontrolled IOP following anterior segment PBRT treatment for AUM were
      prospectively recruited to undergo Baerveldt shunt implantation. Postoperative
      examinations were performed on day 1; weeks 1, 3, 6, 9; months 3, 6, 9, 12 and
      annually thereafter. Surgical success was defined as IOP 21 mm Hg or less and 20%
      reduction from baseline. All complications were recorded. RESULTS: Mean follow-up
      was 15.7 months (SD +/- 8.3 months). Mean interval from irradiation to shunt
      implantation was 2.5 years. Mean preoperative IOP was 31.0 (+/- 10.3) mm Hg; mean
      IOP at last visit was 15.0 (+/- 5.0) mm Hg; mean pre-operative glaucoma
      medications were 3.3 (+/- 1.3); postoperatively 0.7 (+/- 1.3) glaucoma
      medications. Surgical success rate was 86% using glaucoma medications. Four eyes
      had minor postoperative complications, none of which were sight threatening.
      There were no local tumour recurrences or systemic metastases. There were no
      enucleations caused by ocular hypertension. CONCLUSIONS: Baerveldt shunts were
      effective in lowering IOP, with few complications, in eyes treated with total
      anterior segment irradiation for AUM.

PMID- 22628538
TI  - Contemporary clot busting in ST-elevation myocardial infarction: beware of the
      embolus.

PMID- 22628539
TI  - Different behaviour of NOX2 activation in patients with paroxysmal/persistent or
      permanent atrial fibrillation.
AB  - BACKGROUND: NOX2, the catalytic subunit of NADPH oxidase, is suggested to play a
      role in favouring the occurrence of atrial fibrillation (AF) after cardiac
      surgery via formation of reactive oxidant species. However, its role in
      spontaneous AF is still unclear. OBJECTIVE: To define the role of NOX2 and
      isoprostanes, a marker of oxidative stress, in the different settings of AF.
      METHODS: The study was performed on 174 patients with AF (82 with
      paroxysmal/persistent AF and 92 with permanent AF) and 90 controls matched for
      sex, age and atherosclerotic risk factors. Urinary isoprostanes and serum levels
      of soluble NOX2-derived peptide (sNOX2-dp) were measured in each patient.
      RESULTS: Urinary isoprostanes and sNOX2-dp concentrations were significantly
      higher in patients with paroxysmal/persistent AF than in those with permanent AF
      and controls. Compared with controls, patients with permanent AF showed a weak
      increase in sNOX2-dp and no difference in isoprostanes. Multivariable analyses
      demonstrated that baseline values of sNOX2-dp and urinary isoprostanes were
      independently associated with the type of AF (paroxysmal/persistent vs permanent;
      beta=-224, p=0.007 and beta=-231, p=0.005, respectively). A significant
      correlation between sNOX2-dp levels and urinary excretion of isoprostanes was
      also detected (R=0.707, p<0.001). CONCLUSIONS: This study provides evidence that
      NOX2 is upregulated only in patients with paroxysmal/persistent AF and is
      responsible for overproduction of isoprostanes. This finding warrants further
      study to see if inhibition of NOX2 may reduce the risk of paroxysmal/persistent
      AF.

PMID- 22628540
TI  - Is RAMIT reflecting the real world?

PMID- 22628542
TI  - Regulation of shoot and root development through mutual signaling.
AB  - Plants adjust their development in relation to the availability of nutrient
      sources. This necessitates signaling between root and shoot. Aside from the well
      known systemic signaling processes mediated by auxin, cytokinin, and sugars, new
      pathways involving carotenoid-derived hormones have recently been identified. The
      auxin-responsive MAX pathway controls shoot branching through the biosynthesis of
      strigolactone in the roots. The BYPASS1 gene affects the production of an as-yet
      unknown carotenoid-derived substance in roots that promotes shoot development.
      Novel local and systemic mechanisms that control adaptive root development in
      response to nitrogen and phosphorus starvation were recently discovered. Notably,
      the ability of the NITRATE TRANSPORTER 1.1 to transport auxin drew for the first
      time a functional link between auxin, root development, and nitrate availability
      in soil. The study of plant response to phosphorus starvation allowed the
      identification of a systemic mobile miRNA. Deciphering and integrating these
      signaling pathways at the whole-plant level provide a new perspective for
      understanding how plants regulate their development in response to environmental
      cues.

PMID- 22628541
TI  - An epidemiological appraisal of the association between heart rate variability
      and particulate air pollution: a meta-analysis.
AB  - OBJECTIVE: Studies on the association between short-term exposure to ambient air
      pollution and heart rate variability (HRV) suggest that particulate matter (PM)
      exposure is associated with reductions in measures of HRV, but there is
      heterogeneity in the nature and magnitude of this association between studies.
      The authors performed a meta-analysis to determine how consistent this
      association is. DATA SOURCE: The authors searched the Pubmed citation database
      and Web of Knowledge to identify studies on HRV and PM. STUDY SELECTION: Of the
      epidemiologic studies reviewed, 29 provided sufficient details to be considered.
      The meta-analysis included 18667 subjects recruited from the population in
      surveys, studies from patient groups, and from occupationally exposed groups.
      DATA EXTRACTION: Two investigators read all papers and computerised all relevant
      information. RESULTS: The authors computed pooled estimates from a random-effects
      model. In the combined studies, an increase of 10 MUg/m(3) in PM(2.5) was
      associated with significant reductions in the time-domain measurements, including
      low frequency (-1.66%, 95% CI -2.58% to -0.74%) and high frequency (-2.44%, 95%
      CI -3.76% to -1.12%) and in frequency-domain measurements, for SDNN (-0.12%, 95%
      CI -0.22% to -0.03%) and for rMSSD (-2.18%, 95% CI -3.33% to -1.03%). Funnel
      plots suggested that no publication bias was present and a sensitivity analysis
      confirmed the robustness of our combined estimates. CONCLUSION: The meta-analysis
      supports an inverse relationship between HRV, a marker for a worse cardiovascular
      prognosis, and particulate air pollution.

PMID- 22628543
TI  - An update on xylan synthesis.

PMID- 22628544
TI  - XBAT35, a novel Arabidopsis RING E3 ligase exhibiting dual targeting of its
      splice isoforms, is involved in ethylene-mediated regulation of apical hook
      curvature.
AB  - The Arabidopsis XBAT35 is one of five structurally related ankyrin repeat
      containing Really Interesting New Gene (RING) E3 ligases involved in ubiquitin
      mediated protein degradation, which plays key roles in a wide range of cellular
      processes. Here, we show that the XBAT35 gene undergoes alternative splicing,
      generating two transcripts that are constitutively expressed in all plant
      tissues. The two splice variants derive from an exon skipping event that excludes
      an in-frame segment from the XBAT35 precursor mRNA, giving rise to two protein
      isoforms that differ solely in the presence of a nuclear localization signal
      (NLS). Transient expression assays indicate that the isoform lacking the NLS
      localizes in the cytoplasm of plant cells, whereas the other is targeted to the
      nucleus, accumulating in nuclear speckles. Both isoforms are functional E3
      ligases, as assessed by in vitro ubiquitination assays. Two insertion mutant
      alleles and RNA-interference (RNAi) silencing lines for XBAT35 display no evident
      phenotypes under normal growth conditions, but exhibit hypersensitivity to the
      ethylene precursor 1-aminocyclopropane-1-carboxylate (ACC) during apical hook
      exaggeration in the dark, which is rescued by an inhibitor of ethylene
      perception. Independent expression of each XBAT35 splice variant in the mutant
      background indicates that the two isoforms may differentially contribute to
      apical hook formation but are both functional in this ethylene-mediated response.
      Thus, XBAT35 defines a novel player in ethylene signaling involved in negatively
      regulating apical hook curvature, with alternative splicing controlling dual
      targeting of this E3 ubiquitin ligase to the nuclear and cytoplasmic
      compartments.

PMID- 22628546
TI  - Proteomic assessment shows that many endoplasmic reticulum (ER)-resident proteins
      are targeted by N(epsilon)-lysine acetylation in the lumen of the organelle and
      predicts broad biological impact.
AB  - In addition to the nucleus, cytosol, and mitochondrial lumen, N(epsilon)-lysine
      acetylation also occurs in the lumen of the endoplasmic reticulum (ER). However,
      the impact of such an event on ER functions is still unknown. Here, we analyzed
      the "ER acetyl-lysine proteome" by nano-LC-MS/MS and discovered that a large
      number of ER-resident and -transiting proteins undergo N(epsilon)-lysine
      acetylation in the lumen of the organelle. The list of ER-resident proteins
      includes chaperones and enzymes involved with post-translational modification and
      folding. Grouping of all acetylated proteins into major functional categories
      suggests that the ER-based acetylation machinery regulates very diverse
      biological events. As such, it is predicted to play a fundamental role in human
      physiology as well as human pathology.

PMID- 22628545
TI  - Mechanistic role for a novel glucocorticoid-KLF11 (TIEG2) protein pathway in
      stress-induced monoamine oxidase A expression.
AB  - Chronic stress is a risk factor for psychiatric illnesses, including depressive
      disorders, and is characterized by increased blood glucocorticoids and brain
      monoamine oxidase A (MAO A, which degrades monoamine neurotransmitters). This
      study elucidates the relationship between stress-induced MAO A and the
      transcription factor Kruppel-like factor 11 (KLF11, also called TIEG2, a member
      of the Sp/KLF- family), which inhibits cell growth. We report that 1) a
      glucocorticoid (dexamethasone) increases KLF11 mRNA and protein levels in
      cultured neuronal cells; 2) overexpressing KLF11 increases levels of MAO A mRNA
      and enzymatic activity, which is further enhanced by glucocorticoids; in
      contrast, siRNA-mediated KLF11 knockdown reduces glucocorticoid-induced MAO A
      expression in cultured neurons; 3) induction of KLF11 and translocation of KLF11
      from the cytoplasm to the nucleus are key regulatory mechanisms leading to
      increased MAO A catalytic activity and mRNA levels because of direct activation
      of the MAO A promoter via Sp/KLF-binding sites; 4) KLF11 knockout mice show
      reduced MAO A mRNA and catalytic activity in the brain cortex compared with wild
      type mice; and 5) exposure to chronic social defeat stress induces blood
      glucocorticoids and activates the KLF11 pathway in the rat brain, which results
      in increased MAO A mRNA and enzymatic activity. Thus, this study reveals for the
      first time that KLF11 is an MAO A regulator and is produced in response to
      neuronal stress, which transcriptionally activates MAO A. The novel
      glucocorticoid-KLF11-MAO A pathway may play a crucial role in modulating distinct
      pathophysiological steps in stress-related disorders.

PMID- 22628547
TI  - Cytochrome P450-type hydroxylation and epoxidation in a tyrosine-liganded
      hemoprotein, catalase-related allene oxide synthase.
AB  - The ability of hemoproteins to catalyze epoxidation or hydroxylation reactions is
      usually associated with a cysteine as the proximal ligand to the heme, as in
      cytochrome P450 or nitric oxide synthase. Catalase-related allene oxide synthase
      (cAOS) from the coral Plexaura homomalla, like catalase itself, has tyrosine as
      the proximal heme ligand. Its natural reaction is to convert 8R-hydroperoxy
      eicosatetraenoic acid (8R-HPETE) to an allene epoxide, a reaction activated by
      the ferric heme, forming product via the Fe(IV)-OH intermediate, Compound II.
      Here we oxidized cAOS to Compound I (Fe(V)=O) using the oxygen donor
      iodosylbenzene and investigated the catalytic competence of the enzyme. 8R
      hydroxyeicosatetraenoic acid (8R-HETE), the hydroxy analog of the natural
      substrate, normally unreactive with cAOS, was thereby epoxidized
      stereospecifically on the 9,10 double bond to form 8R-hydroxy-9R,10R-trans-epoxy
      eicosa-5Z,11Z,14Z-trienoic acid as the predominant product; the turnover was 1/s
      using 100 MUm iodosylbenzene. The enantiomer, 8S-HETE, was epoxidized
      stereospecifically, although with less regiospecificity, and was hydroxylated on
      the 13- and 16-carbons. Arachidonic acid was converted to two major products, 8R
      HETE and 8R,9S-eicosatrienoic acid (8R,9S-EET), plus other chiral monoepoxides
      and bis-allylic 10S-HETE. Linoleic acid was epoxidized, whereas stearic acid was
      not metabolized. We conclude that when cAOS is charged with an oxygen donor, it
      can act as a stereospecific monooxygenase. Our results indicate that in the
      tyrosine-liganded cAOS, a catalase-related hemoprotein in which a polyunsaturated
      fatty acid can enter the active site, the enzyme has the potential to mimic the
      activities of typical P450 epoxygenases and some capabilities of P450
      hydroxylases.

PMID- 22628548
TI  - Ezrin-anchored protein kinase A coordinates phosphorylation-dependent disassembly
      of a NHERF1 ternary complex to regulate hormone-sensitive phosphate transport.
AB  - Congenital defects in the Na/H exchanger regulatory factor-1 (NHERF1) are linked
      to disordered phosphate homeostasis and skeletal abnormalities in humans. In the
      kidney, these mutations interrupt parathyroid hormone (PTH)-responsive
      sequestration of the renal phosphate transporter, Npt2a, with ensuing urinary
      phosphate wasting. We now report that NHERF1, a modular PDZ domain scaffolding
      protein, coordinates the assembly of an obligate ternary complex with Npt2a and
      the PKA-anchoring protein ezrin to facilitate PTH-responsive cAMP signaling
      events. Activation of ezrin-anchored PKA initiates NHERF1 phosphorylation to
      disassemble the ternary complex, release Npt2a, and thereby inhibit phosphate
      transport. Loss-of-function mutations stabilize an inactive NHERF1 conformation
      that we show is refractory to PKA phosphorylation and impairs assembly of the
      ternary complex. Compensatory mutations introduced in mutant NHERF1 re-establish
      the integrity of the ternary complex to permit phosphorylation of NHERF1 and
      rescue PTH action. These findings offer new insights into a novel macromolecular
      mechanism for the physiological action of a critical ternary complex, where
      anchored PKA coordinates the assembly and turnover of the Npt2a-NHERF1-ezrin
      complex.

PMID- 22628549
TI  - Quantitative analysis of prenylated RhoA interaction with its chaperone, RhoGDI.
AB  - Small GTPases of the Rho family regulate cytoskeleton remodeling, cell polarity,
      and transcription, as well as the cell cycle, in eukaryotic cells. Membrane
      delivery and recycling of the Rho GTPases is mediated by Rho GDP dissociation
      inhibitor (RhoGDI), which forms a stable complex with prenylated Rho GTPases. We
      analyzed the interaction of RhoGDI with the active and inactive forms of
      prenylated and unprenylated RhoA. We demonstrate that RhoGDI binds the prenylated
      form of RhoA.GDP with unexpectedly high affinity (K(d) = 5 pm). The very long
      half-life of the complex is reduced 25-fold on RhoA activation, with a
      concomitant reduction in affinity (K(d) = 3 nm). The 2.8-A structure of the
      RhoA.guanosine 5'-[beta,gamma-imido] triphosphate (GMPPNP).RhoGDI complex
      demonstrated that complex formation forces the activated RhoA into a GDP-bound
      conformation in the absence of nucleotide hydrolysis. We demonstrate that
      membrane extraction of Rho GTPase by RhoGDI is a thermodynamically favored
      passive process that operates through a series of progressively tighter
      intermediates, much like the one that is mediated by RabGDI.

PMID- 22628550
TI  - Methionine sulfoxide reductases preferentially reduce unfolded oxidized proteins
      and protect cells from oxidative protein unfolding.
AB  - Reduction of methionine sulfoxide (MetO) residues in proteins is catalyzed by
      methionine sulfoxide reductases A (MSRA) and B (MSRB), which act in a
      stereospecific manner. Catalytic properties of these enzymes were previously
      established mostly using low molecular weight MetO-containing compounds, whereas
      little is known about the catalysis of MetO reduction in proteins, the
      physiological substrates of MSRA and MSRB. In this work we exploited an NADPH
      dependent thioredoxin system and determined the kinetic parameters of yeast MSRA
      and MSRB using three different MetO-containing proteins. Both enzymes showed
      Michaelis-Menten kinetics with the K(m) lower for protein than for small MetO
      containing substrates. MSRA reduced both oxidized proteins and low molecular
      weight MetO-containing compounds with similar catalytic efficiencies, whereas
      MSRB was specialized for the reduction of MetO in proteins. Using oxidized
      glutathione S-transferase as a model substrate, we showed that both MSR types
      were more efficient in reducing MetO in unfolded than in folded proteins and that
      their activities increased with the unfolding state. Biochemical quantification
      and identification of MetO reduced in the substrates by mass spectrometry
      revealed that the increased activity was due to better access to oxidized MetO in
      unfolded proteins; it also showed that MSRA was intrinsically more active with
      unfolded proteins regardless of MetO availability. Moreover, MSRs most
      efficiently protected cells from oxidative stress that was accompanied by protein
      unfolding. Overall, this study indicates that MSRs serve a critical function in
      the folding process by repairing oxidatively damaged nascent polypeptides and
      unfolded proteins.

PMID- 22628551
TI  - Ring finger protein 149 is an E3 ubiquitin ligase active on wild-type v-Raf
      murine sarcoma viral oncogene homolog B1 (BRAF).
AB  - Members of the RAF family (ARAF, BRAF, and CRAF/RAF-1) are involved in a variety
      of cellular activities, including growth, survival, differentiation, and
      transformation. An oncogene encodes BRAF, the function of which is linked to MEK
      activation. BRAF is the most effective RAF kinase in terms of induction of
      MEK/ERK activity. However, the mechanisms involved in BRAF regulation remain
      unclear. In the present work, we used a tandem affinity purification approach to
      show that RNF149 (RING finger protein 149) interacts with wild-type BRAF. The
      latter protein is a RING domain-containing E3 ubiquitin ligase involved in
      control of gene transcription, translation, cytoskeletal organization, cell
      adhesion, and epithelial development. We showed that RNF149 bound directly to the
      C-terminal kinase-containing domain of wild-type BRAF and induced ubiquitination,
      followed by proteasome-dependent degradation, of the latter protein.
      Functionally, RNF149 attenuated the increase in cell growth induced by wild-type
      BRAF. However, RNF149 did not bind to mutant BRAF or induce ubiquitination
      thereof. Thus, we show that RNF149 is an E3 ubiquitin ligase active on wild-type
      BRAF.

PMID- 22628552
TI  - Critical roles of the mitochondrial complex II in oocyst formation of rodent
      malaria parasite Plasmodium berghei.
AB  - It is generally accepted that the mitochondria play central roles in energy
      production of most eukaryotes. In contrast, it has been thought that Plasmodium
      spp., the causative agent of malaria, rely mainly on cytosolic glycolysis but not
      mitochondrial oxidative phosphorylation for energy production during blood
      stages. However, Plasmodium spp. possesses all genes necessary for the
      tricarboxylic acid (TCA) cycle and most of the genes for electron transport chain
      (ETC) enzymes. Therefore, it remains elusive whether oxidative phosphorylation is
      essential for the parasite survival. To elucidate the role of TCA metabolism and
      ETC in malaria parasites, we deleted the gene for flavoprotein (Fp) subunit,
      Pbsdha, one of four components of complex II, a catalytic subunit for succinate
      dehydrogenase activity. The Pbsdha(-) parasite grew normally at blood stages in
      mouse. In contrast, ookinete formation of Pbsdha(-) parasites in the mosquito
      stage was severely impaired. Finally, Pbsdha(-) ookinetes failed in oocyst
      formation, leading to complete malaria transmission blockade. These results
      suggest that malaria parasite may switch the energy metabolism from glycolysis to
      oxidative phosphorylation to adapt to the insect vector where glucose is not
      readily available for ATP production.

PMID- 22628553
TI  - Recurrent hemizygous deletions in cancers may optimize proliferative potential.
AB  - Tumors exhibit numerous recurrent hemizygous focal deletions that contain no
      known tumor suppressors and are poorly understood. To investigate whether these
      regions contribute to tumorigenesis, we searched genetically for genes with
      cancer-relevant properties within these hemizygous deletions. We identified STOP
      and GO genes, which negatively and positively regulate proliferation,
      respectively. STOP genes include many known tumor suppressors, whereas GO genes
      are enriched for essential genes. Analysis of their chromosomal distribution
      revealed that recurring deletions preferentially overrepresent STOP genes and
      underrepresent GO genes. We propose a hypothesis called the cancer gene island
      model, whereby gene islands encompassing high densities of STOP genes and low
      densities of GO genes are hemizygously deleted to maximize proliferative fitness
      through cumulative haploinsufficiencies. Because hundreds to thousands of genes
      are hemizygously deleted per tumor, this mechanism may help to drive
      tumorigenesis across many cancer types.

PMID- 22628554
TI  - Identification and functional expression of the mitochondrial pyruvate carrier.
AB  - The transport of pyruvate, the end product of glycolysis, into mitochondria is an
      essential process that provides the organelle with a major oxidative fuel.
      Although the existence of a specific mitochondrial pyruvate carrier (MPC) has
      been anticipated, its molecular identity remained unknown. We report that MPC is
      a heterocomplex formed by two members of a family of previously uncharacterized
      membrane proteins that are conserved from yeast to mammals. Members of the MPC
      family were found in the inner mitochondrial membrane, and yeast mutants lacking
      MPC proteins showed severe defects in mitochondrial pyruvate uptake. Coexpression
      of mouse MPC1 and MPC2 in Lactococcus lactis promoted transport of pyruvate
      across the membrane. These observations firmly establish these proteins as
      essential components of the MPC.

PMID- 22628555
TI  - Structural basis for prereceptor modulation of plant hormones by GH3 proteins.
AB  - Acyl acid amido synthetases of the GH3 family act as critical prereceptor
      modulators of plant hormone action; however, the molecular basis for their
      hormone selectivity is unclear. Here, we report the crystal structures of
      benzoate-specific Arabidopsis thaliana AtGH3.12/PBS3 and jasmonic acid-specific
      AtGH3.11/JAR1. These structures, combined with biochemical analysis, define
      features for the conjugation of amino acids to diverse acyl acid substrates and
      highlight the importance of conformational changes in the carboxyl-terminal
      domain for catalysis. We also identify residues forming the acyl acid binding
      site across the GH3 family and residues critical for amino acid recognition. Our
      results demonstrate how a highly adaptable three-dimensional scaffold is used for
      the evolution of promiscuous activity across an enzyme family for modulation of
      plant signaling molecules.

PMID- 22628556
TI  - The structures of COPI-coated vesicles reveal alternate coatomer conformations
      and interactions.
AB  - Transport between compartments of eukaryotic cells is mediated by coated
      vesicles. The archetypal protein coats COPI, COPII, and clathrin are conserved
      from yeast to human. Structural studies of COPII and clathrin coats assembled in
      vitro without membranes suggest that coat components assemble regular cages with
      the same set of interactions between components. Detailed three-dimensional
      structures of coated membrane vesicles have not been obtained. Here, we solved
      the structures of individual COPI-coated membrane vesicles by cryoelectron
      tomography and subtomogram averaging of in vitro reconstituted budding reactions.
      The coat protein complex, coatomer, was observed to adopt alternative
      conformations to change the number of other coatomers with which it interacts and
      to form vesicles with variable sizes and shapes. This represents a fundamentally
      different basis for vesicle coat assembly.

PMID- 22628557
TI  - A reduced organic carbon component in martian basalts.
AB  - The source and nature of carbon on Mars have been a subject of intense
      speculation. We report the results of confocal Raman imaging spectroscopy on 11
      martian meteorites, spanning about 4.2 billion years of martian history. Ten of
      the meteorites contain abiotic macromolecular carbon (MMC) phases detected in
      association with small oxide grains included within high-temperature minerals.
      Polycyclic aromatic hydrocarbons were detected along with MMC phases in Dar al
      Gani 476. The association of organic carbon within magmatic minerals indicates
      that martian magmas favored precipitation of reduced carbon species during
      crystallization. The ubiquitous distribution of abiotic organic carbon in martian
      igneous rocks is important for understanding the martian carbon cycle and has
      implications for future missions to detect possible past martian life.

PMID- 22628559
TI  - Hesperian age for western Medusae Fossae Formation, Mars.
AB  - The Medusae Fossae Formation (MFF) on Mars is an intensely eroded deposit north
      of the cratered highlands. It is widely thought that MFF materials were emplaced
      through ignimbrite eruptions. Recent geologic mapping of western MFF identified
      outliers of MFF materials well beyond the previously mapped western extent for
      the deposit, including outliers close to Gale crater. We report counts of impact
      craters on the MFF units that have implications for our understanding of the
      general history of MFF and the uppermost layered materials on the Gale crater
      mound.

PMID- 22628558
TI  - A mitochondrial pyruvate carrier required for pyruvate uptake in yeast,
      Drosophila, and humans.
AB  - Pyruvate constitutes a critical branch point in cellular carbon metabolism. We
      have identified two proteins, Mpc1 and Mpc2, as essential for mitochondrial
      pyruvate transport in yeast, Drosophila, and humans. Mpc1 and Mpc2 associate to
      form an ~150-kilodalton complex in the inner mitochondrial membrane. Yeast and
      Drosophila mutants lacking MPC1 display impaired pyruvate metabolism, with an
      accumulation of upstream metabolites and a depletion of tricarboxylic acid cycle
      intermediates. Loss of yeast Mpc1 results in defective mitochondrial pyruvate
      uptake, and silencing of MPC1 or MPC2 in mammalian cells impairs pyruvate
      oxidation. A point mutation in MPC1 provides resistance to a known inhibitor of
      the mitochondrial pyruvate carrier. Human genetic studies of three families with
      children suffering from lactic acidosis and hyperpyruvatemia revealed a causal
      locus that mapped to MPC1, changing single amino acids that are conserved
      throughout eukaryotes. These data demonstrate that Mpc1 and Mpc2 form an
      essential part of the mitochondrial pyruvate carrier.

PMID- 22628560
TI  - Overexpression of GSH1 gene mimics transcriptional response to low temperature
      during seed vernalization treatment of Arabidopsis.
AB  - Keeping imbibed seeds at low temperatures for a certain period, so-called seed
      vernalization (SV) treatment, promotes seed germination and subsequent flowering
      in various plants. Vernalization-promoting flowering requires GSH. However, we
      show here that increased GSH biosynthesis partially mimics SV treatment in
      Arabidopsis thaliana. SV treatment (keeping imbibed seeds at 4 degrees C for 24
      h) induced a specific pattern of gene expression and promoted subsequent
      flowering in WT A. thaliana. A similar pattern was observed at 22 degrees C in
      transgenic (35S-GSH1) plants overexpressing the gamma-glutamylcysteine synthetase
      gene GSH1, coding for an enzyme limiting GSH biosynthesis, under the control of
      the cauliflower mosaic virus 35S promoter. This pattern of gene expression was
      further strengthened at 4 degrees C and indistinguishable from the WT pattern at
      4 degrees C. However, flowering in 35S-GSH1 plants was less responsive to SV
      treatment than in WT plants. There was a difference in the transcript behavior of
      the flowering repressor FLC between WT and 35S-GSH1 plants. Unlike other genes
      responsive to SV treatment, the SV-dependent decrease in FLC in WT plants was
      reversed in 35S-GSH1 plants. SV treatment increased the GSSG level in WT seeds
      while its level was high in 35S-GSH1 plants, even at a non-vernalizing
      temperature. Taking into consideration that low temperatures stimulate GSH
      biosynthesis and cause oxidative stress, GSSG is considered to trigger a low
      temperature response, although enhanced GSH synthesis was not enough to
      completely mimic the SV treatment.

PMID- 22628561
TI  - Wave-particle dualism and complementarity unraveled by a different mode.
AB  - The precise knowledge of one of two complementary experimental outcomes prevents
      us from obtaining complete information about the other one. This formulation of
      Niels Bohr's principle of complementarity when applied to the paradigm of wave
      particle dualism--that is, to Young's double-slit experiment--implies that the
      information about the slit through which a quantum particle has passed erases
      interference. In the present paper we report a double-slit experiment using two
      photons created by spontaneous parametric down-conversion where we observe
      interference in the signal photon despite the fact that we have located it in one
      of the slits due to its entanglement with the idler photon. This surprising
      aspect of complementarity comes to light by our special choice of the TEM(01)
      pump mode. According to quantum field theory the signal photon is then in a
      coherent superposition of two distinct wave vectors giving rise to interference
      fringes analogous to two mechanical slits.

PMID- 22628562
TI  - Direct magnetic resonance detection of myelin and prospects for quantitative
      imaging of myelin density.
AB  - Magnetic resonance imaging has previously demonstrated its potential for
      indirectly mapping myelin density, either by relaxometric detection of myelin
      water or magnetization transfer. Here, we investigated whether myelin can be
      detected and possibly quantified directly. We identified the spectrum of myelin
      in the spinal cord in situ as well as in myelin lipids extracted via a sucrose
      gradient method, and investigated its spectral properties. High-resolution
      solution NMR spectroscopy showed the extract composition to be in agreement with
      myelin's known chemical make-up. The 400-MHz (1)H spectrum of the myelin extract,
      at 20  degrees C (room temperature) and 37  degrees C, consists of a narrow water
      resonance superimposed on a broad envelope shifted ~3.5 ppm upfield, suggestive
      of long-chain methylene protons. Superimposed on this signal are narrow
      components resulting from functional groups matching the chemical shifts of the
      constituents making up myelin lipids. The spectrum could be modeled as a sum of
      super-Lorentzians with a T(2)* distribution covering a wide range of values
      (0.008-26 ms). Overall, there was a high degree of similarity between the
      spectral properties of extracted myelin lipids and those found in neural tissue.
      The normalized difference spectrum had the hallmarks of membrane proteins, not
      present in the myelin extract. Using 3D radially ramp-sampled proton MRI, with a
      combination of adiabatic inversion and echo subtraction, the feasibility of
      direct myelin imaging in situ is demonstrated. Last, the integrated signal from
      myelin suspensions is shown, both spectroscopically and by imaging, to scale with
      concentration, suggesting the potential for quantitative determination of myelin
      density.

PMID- 22628563
TI  - Data-driven unbiased curation of the TP53 tumor suppressor gene mutation database
      and validation by ultradeep sequencing of human tumors.
AB  - Cancer mutation databases are expected to play central roles in personalized
      medicine by providing targets for drug development and biomarkers to tailor
      treatments to each patient. The accuracy of reported mutations is a critical
      issue that is commonly overlooked, which leads to mutation databases that include
      a sizable number of spurious mutations, either sequencing errors or passenger
      mutations. Here we report an analysis of the latest version of the TP53 mutation
      database, including 34,453 mutations. By using several data-driven methods on
      multiple independent quality criteria, we obtained a quality score for each
      report contributing to the database. This score can now be used to filter for
      high-confidence mutations and reports within the database. Sequencing the entire
      TP53 gene from various types of cancer using next-generation sequencing with
      ultradeep coverage validated our approach for curation. In summary, 9.7% of all
      collected studies, mostly comprising numerous tumors with multiple infrequent
      TP53 mutations, should be excluded when analyzing TP53 mutations. Thus, by
      combining statistical and experimental analyses, we provide a curated mutation
      database for TP53 mutations and a framework for mutation database analysis.

PMID- 22628564
TI  - Engineering rotor ring stoichiometries in the ATP synthase.
AB  - ATP synthase membrane rotors consist of a ring of c-subunits whose stoichiometry
      is constant for a given species but variable across different ones. We
      investigated the importance of c/c-subunit contacts by site-directed mutagenesis
      of a conserved stretch of glycines (GxGxGxGxG) in a bacterial c(11) ring.
      Structural and biochemical studies show a direct, specific influence on the c
      subunit stoichiometry, revealing c(<11), c(12), c(13), c(14), and c(>14) rings.
      Molecular dynamics simulations rationalize this effect in terms of the energetics
      and geometry of the c-subunit interfaces. Quantitative data from a spectroscopic
      interaction study demonstrate that the complex assembly is independent of the c
      ring size. Real-time ATP synthesis experiments in proteoliposomes show the mutant
      enzyme, harboring the larger c(12) instead of c(11), is functional at lower ion
      motive force. The high degree of compliance in the architecture of the ATP
      synthase rotor offers a rationale for the natural diversity of c-ring
      stoichiometries, which likely reflect adaptations to specific bioenergetic
      demands. These results provide the basis for bioengineering ATP synthases with
      customized ion-to-ATP ratios, by sequence modifications.

PMID- 22628565
TI  - Cenozoic climate change shaped the evolutionary ecophysiology of the Cupressaceae
      conifers.
AB  - The Cupressaceae clade has the broadest diversity in habitat and morphology of
      any conifer family. This clade is characterized by highly divergent physiological
      strategies, with deciduous swamp-adapted genera-like Taxodium at one extreme, and
      evergreen desert genera-like Cupressus at the other. The size disparity within
      the Cupressaceae is equally impressive, with members ranging from 5-m-tall
      juniper shrubs to 100-m-tall redwood trees. Phylogenetic studies demonstrate that
      despite this variation, these taxa all share a single common ancestor; by
      extension, they also share a common ancestral habitat. Here, we use a common
      garden approach to compare xylem and leaf-level physiology in this family. We
      then apply comparative phylogenetic methods to infer how Cenozoic climatic change
      shaped the morphological and physiological differences between modern-day members
      of the Cupressaceae. Our data show that drought-resistant crown clades (the
      Cupressoid and Callitroid clades) most likely evolved from drought-intolerant
      Mesozoic ancestors, and that this pattern is consistent with proposed shifts in
      post-Eocene paleoclimates. We also provide evidence that within the Cupressaceae,
      the evolution of drought-resistant xylem is coupled to increased carbon
      investment in xylem tissue, reduced xylem transport efficiency, and at the leaf
      level, reduced photosynthetic capacity. Phylogenetically based analyses suggest
      that the ancestors of the Cupressaceae were dependent upon moist habitats, and
      that drought-resistant physiology developed along with increasing habitat aridity
      from the Oligocene onward. We conclude that the modern biogeography of the
      Cupressaceae conifers was shaped in large part by their capacity to adapt to
      drought.

PMID- 22628566
TI  - In vitro loading of human cohesin on DNA by the human Scc2-Scc4 loader complex.
AB  - The loading of cohesin onto chromatin requires the heterodimeric complex sister
      chromatid cohesion (Scc)2 and Scc4 (Scc2/4), which is highly conserved in all
      species. Here, we describe the purification of the human (h)-Scc2/4 and show that
      it interacts with h-cohesin and the heterodimeric Smc1-Smc3 complex but not with
      the Smc1 or Smc3 subunit alone. We demonstrate that both h-Scc2/4 and h-cohesin
      are loaded onto dsDNA containing the prereplication complex (pre-RC) generated in
      vitro by Xenopus high-speed soluble extracts. The addition of geminin, which
      blocks pre-RC formation, prevents the loading of Scc2/4 and cohesin. Xenopus
      extracts depleted of endogenous Scc2/4 with specific antibodies, although able to
      form pre-RCs, did not support cohesin loading unless supplemented with purified h
      Scc2/4. The results presented here indicate that the Xenopus or h-Scc2/4 complex
      supports the loading of Xenopus and/or h-cohesin onto pre-RCs formed by Xenopus
      high-speed extracts. We show that cohesin loaded onto pre-RCs either by h-Scc2/4
      and/or the Xenopus complex was dissociated from chromatin by low salt extraction,
      similar to cohesin loaded onto chromatin in G(1) by HeLa cells in vivo.
      Replication of cohesin-loaded DNA, both in vitro and in vivo, markedly increased
      the stability of cohesin associated with DNA. Collectively, these in vitro
      findings partly recapitulate the in vivo pathway by which sister chromatids are
      linked together, leading to cohesion.

PMID- 22628567
TI  - Eukaryotic elongation factor 1 complex subunits are critical HIV-1 reverse
      transcription cofactors.
AB  - Cellular proteins have been implicated as important for HIV-1 reverse
      transcription, but whether any are reverse transcription complex (RTC) cofactors
      or affect reverse transcription indirectly is unclear. Here we used protein
      fractionation combined with an endogenous reverse transcription assay to identify
      cellular proteins that stimulated late steps of reverse transcription in vitro.
      We identified 25 cellular proteins in an active protein fraction, and here we
      show that the eEF1A and eEF1G subunits of eukaryotic elongation factor 1 (eEF1)
      are important components of the HIV-1 RTC. eEF1A and eEF1G were identified in
      fractionated human T-cell lysates as reverse transcription cofactors, as their
      removal ablated the ability of active protein fractions to stimulate late reverse
      transcription in vitro. We observed that the p51 subunit of reverse transcriptase
      and integrase, two subunits of the RTC, coimmunoprecipitated with eEF1A and
      eEF1G. Moreover eEF1A and eEF1G associated with purified RTCs and colocalized
      with reverse transcriptase following infection of cells. Reverse transcription in
      cells was sharply down-regulated when eEF1A or eEF1G levels were reduced by siRNA
      treatment as a result of reduced levels of RTCs in treated cells. The combined
      evidence indicates that these eEF1 subunits are critical RTC stability cofactors
      required for efficient completion of reverse transcription. The identification of
      eEF1 subunits as unique RTC components provides a basis for further
      investigations of reverse transcription and trafficking of the RTC to the
      nucleus.

PMID- 22628568
TI  - Flawed analysis of the possibility of air capture.

PMID- 22628569
TI  - Direct reprogramming for cardiac regeneration: from dream to reality.

PMID- 22628570
TI  - Novel role for the regulation of mitochondrial fission by hypoxia inducible
      factor-1alpha in the control of smooth muscle remodeling and progression of
      pulmonary hypertension.

PMID- 22628571
TI  - Ryanodine receptor phosphorylation and heart failure: phasing out S2808 and
      "criminalizing" S2814.

PMID- 22628573
TI  - Margaret Kirby: a cardiologist against the odds. Interview by Ruth Williams.

PMID- 22628572
TI  - Biased DNA segregation during stem cell division.

PMID- 22628575
TI  - Iroquois homeodomain transcription factors in heart development and function.
AB  - Numerous cardiac transcription factors play overlapping roles in both the
      specification and proliferation of the cardiac tissues and chambers during heart
      development. It has become increasingly apparent that cardiac transcription
      factors also play critical roles in the regulation of expression of many
      functional genes in the prenatal and postnatal hearts. Accordingly, mutations of
      cardiac transcription factors cannot only result in congenital heart defects but
      also alter heart function thereby predisposing to heart disease and cardiac
      arrhythmias. In this review, we summarize the roles of Iroquois homeobox (Irx)
      family of transcription factors in heart development and function. In all, 6 Irx
      genes are expressed with distinct and overlapping patterns in the mammalian
      heart. Studies in several animal models demonstrate that Irx genes are important
      for the establishment of ventricular chamber properties, the ventricular
      conduction system, as well as heterogeneity of the ventricular repolarization.
      The molecular mechanisms by which Irx proteins regulate gene expression and the
      clinical relevance of Irx functions in the heart are discussed.

PMID- 22628574
TI  - Cardiac-specific inducible and conditional gene targeting in mice.
AB  - Mouse genetic engineering has revolutionized our understanding of the molecular
      and genetic basis of heart development and disease. This technology involves
      conditional tissue-specific and temporal transgenic and gene targeting
      approaches, as well as introduction of polymorphisms into the mouse genome. These
      approaches are increasingly used to elucidate the genetic pathways underlying
      tissue homeostasis, physiology, and pathophysiology of adult heart. They have
      also led to the development of clinically relevant models of human cardiac
      diseases. Here, we review the technologies and their limitations in general and
      the cardiovascular research community in particular.

PMID- 22628576
TI  - Gene regulatory networks in cardiac conduction system development.
AB  - The cardiac conduction system is a specialized tract of myocardial cells
      responsible for maintaining normal cardiac rhythm. Given its critical role in
      coordinating cardiac performance, a detailed analysis of the molecular mechanisms
      underlying conduction system formation should inform our understanding of
      arrhythmia pathophysiology and affect the development of novel therapeutic
      strategies. Historically, the ability to distinguish cells of the conduction
      system from neighboring working myocytes presented a major technical challenge
      for performing comprehensive mechanistic studies. Early lineage tracing
      experiments suggested that conduction cells derive from cardiomyocyte precursors,
      and these claims have been substantiated by using more contemporary approaches.
      However, regional specialization of conduction cells adds an additional layer of
      complexity to this system, and it appears that different components of the
      conduction system utilize unique modes of developmental formation. The
      identification of numerous transcription factors and their downstream target
      genes involved in regional differentiation of the conduction system has provided
      insight into how lineage commitment is achieved. Furthermore, by adopting cutting
      edge genetic techniques in combination with sophisticated phenotyping
      capabilities, investigators have made substantial progress in delineating the
      regulatory networks that orchestrate conduction system formation and their role
      in cardiac rhythm and physiology. This review describes the connectivity of these
      gene regulatory networks in cardiac conduction system development and discusses
      how they provide a foundation for understanding normal and pathological human
      cardiac rhythms.

PMID- 22628577
TI  - Ryanodine receptor current amplitude controls Ca2+ sparks in cardiac muscle.
AB  - RATIONALE: In cardiac muscle, Ca(2+)-induced Ca(2+) release (CICR) from the
      sarcoplasmic reticulum (SR) is mediated by ryanodine receptor (RyR) Ca(2+)
      release channels. The inherent positive feedback of CICR is normally well
      controlled. Understanding this control mechanism is a priority because its
      malfunction has life-threatening consequences. OBJECTIVE: We show that CICR local
      control is governed by SR Ca(2+) load, largely because load determines the single
      RyR current amplitude that drives inter-RyR CICR. METHODS AND RESULTS: We
      differentially manipulated single RyR Ca(2+) flux amplitude and SR Ca(2+) load in
      permeabilized ventricular myocytes as an endogenous cell biology model of the
      heart. Large RyR-permeable organic cations were used to interfere with Ca(2+)
      conductance through the open RyR pore. Single-channel studies show this
      attenuates current amplitude without altering other aspects of RyR function. In
      cells, the same experimental maneuver increased resting SR Ca(2+) load. Despite
      the increased load, Ca(2+) spark (inter-RyR CICR events) frequency decreased and
      sparks terminated earlier. CONCLUSIONS: Spark local control follows single RyR
      current amplitude, not simply SR Ca(2+) load. Spark frequency increases with load
      because spontaneous RyR openings at high loads produce larger currents (ie, a
      larger CICR trigger signal). Sparks terminate when load falls to the point at
      which single RyR current amplitude is no longer sufficient to sustain inter-RyR
      CICR. Thus, RyRs that spontaneously close no longer reopen and local Ca(2+)
      release ends.

PMID- 22628579
TI  - Neuromuscular training for chronic ankle instability.

PMID- 22628580
TI  - Habitual physical activity after total knee replacement.
AB  - BACKGROUND: Previous studies on physical activity after total knee arthroplasty
      (TKA) concentrated mainly on a return to sports activities. OBJECTIVE: The
      objectives of this study were to determine the habitual physical activity
      behavior of people who had undergone TKA (TKA group) 1 to 5 years after surgery
      and to examine to what extent they adhered to international guidelines for health
      enhancing physical activity. Additional aims were to compare younger (<65 years
      old) and older (>= 65 years old) people as well as men and women in the TKA group
      and to compare the results for the TKA group with those for a sex- and age
      matched normative population (normative group). DESIGN: This investigation was a
      cohort study. METHODS: All people who had a primary TKA at 1 of 2 participating
      hospitals between 2002 and 2006 were sent the Short Questionnaire to Assess
      Health-Enhancing Physical Activity at least 1 year after surgery. RESULTS: The
      TKA group spent, on average, 1,347 minutes per week on physical activity, most of
      which was light-intensity activity (780 minutes per week). Participants younger
      than 65 years of age spent significantly more time on physical activity than
      participants 65 years of age or older. There was no significant difference
      between male and female participants. Compared with the sex- and age-matched
      normative group, the TKA group spent significantly less time on the total amount
      of physical activity per week and met the guidelines for health-enhancing
      physical activity less often (55% versus 64%). LIMITATIONS: A self-administered
      questionnaire was used to assess habitual physical activity, and presurgery data
      on physical activity were not available. CONCLUSIONS: Almost half of the TKA
      group did not meet the health-enhancing physical activity guidelines, and the TKA
      group was not as physically active as the normative group. People who have
      undergone TKA should be encouraged to be more physically active.

PMID- 22628578
TI  - Severe hyperhomocysteinemia promotes bone marrow-derived and resident
      inflammatory monocyte differentiation and atherosclerosis in LDLr/CBS-deficient
      mice.
AB  - RATIONALE: Hyperhomocysteinemia (HHcy) accelerates atherosclerosis and increases
      inflammatory monocytes (MC) in peripheral tissues. However, its causative role in
      atherosclerosis is not well established and its effect on vascular inflammation
      has not been studied. The underlying mechanism is unknown. OBJECTIVE: This study
      examined the causative role of HHcy in atherogenesis and its effect on
      inflammatory MC differentiation. METHODS AND RESULTS: We generated a novel HHcy
      and hyperlipidemia mouse model, in which cystathionine beta-synthase (CBS) and
      low-density lipoprotein receptor (LDLr) genes were deficient (Ldlr(-/-) Cbs(
      /+)). Severe HHcy (plasma homocysteine (Hcy)=275 MUmol/L) was induced by a high
      methionine diet containing sufficient basal levels of B vitamins. Plasma Hcy
      levels were lowered to 46 MUmol/L from 244 MUmol/L by vitamin supplementation,
      which elevated plasma folate levels. Bone marrow (BM)-derived cells were traced
      by the transplantation of BM cells from enhanced green fluorescent protein (EGFP)
      transgenic mice after sublethal irradiation of the recipient. HHcy accelerated
      atherosclerosis and promoted Ly6C(high) inflammatory MC differentiation of both
      BM and tissue origins in the aortas and peripheral tissues. It also elevated
      plasma levels of TNF-alpha, IL-6, and MCP-1; increased vessel wall MC
      accumulation; and increased macrophage maturation. Hcy-lowering therapy reversed
      HHcy-induced lesion formation, plasma cytokine increase, and blood and vessel
      inflammatory MC (Ly6C(high+middle)) accumulation. Plasma Hcy levels were
      positively correlated with plasma levels of proinflammatory cytokines. In primary
      mouse splenocytes, L-Hcy promoted rIFNgamma-induced inflammatory MC
      differentiation, as well as increased TNF-alpha, IL-6, and superoxide anion
      production in inflammatory MC subsets. Antioxidants and folic acid reversed L-Hcy
      induced inflammatory MC differentiation and oxidative stress in inflammatory MC
      subsets. CONCLUSIONS: HHcy causes vessel wall inflammatory MC differentiation and
      macrophage maturation of both BM and tissue origins, leading to atherosclerosis
      via an oxidative stress-related mechanism.

PMID- 22628581
TI  - Influence of fear-avoidance beliefs on functional status outcomes for people with
      musculoskeletal conditions of the shoulder.
AB  - BACKGROUND: The influence of elevated fear-avoidance beliefs on change in
      functional status is unclear. OBJECTIVE: The purpose of this study was to
      determine the influence of fear-avoidance on recovery of functional status during
      rehabilitation for people with shoulder impairments. DESIGN: A retrospective
      longitudinal cohort study was conducted. METHODS: Data were collected from 3,362
      people with musculoskeletal conditions of the shoulder receiving rehabilitation.
      At intake and discharge, upper-extremity function was measured using the shoulder
      Computerized Adaptive Test. Pain intensity was measured using an 11-point
      numerical rating scale. Completion rate at discharge was 57% for function and 47%
      for pain intensity. A single-item screen was used to classify patients into
      groups with low versus elevated fear-avoidance beliefs at intake. A general
      linear model (GLM) was used to describe how change in function is affected by
      fear avoidance in 8 disease categories. This study also accounted for within
      clinic correlation and controlled for other important predictors of functional
      change in functional status, including various demographic and health-related
      variables. The parameters of the GLM and their standard errors were estimated
      with the weighted generalized estimating equations method. RESULTS: Functional
      change was predicted by the interaction between fear and disease categories. On
      further examination of 8 disease categories using GLM adjusted for other
      confounders, improvement in function was greater for the low fear group than for
      the elevated fear group among people with muscle, tendon, and soft tissue
      disorders (Delta=1.37, P<.01) and those with osteopathies, chondropathies, and
      acquired musculoskeletal deformities (Delta=5.52, P<.02). These differences were
      below the minimal detectable change. Limitations Information was not available on
      whether therapists used information on level of fear to implement treatment
      plans. CONCLUSIONS: The influence of fear-avoidance beliefs on change in
      functional status varies among specific shoulder impairments.

PMID- 22628582
TI  - A survey of the McKenzie Classification System in the Extremities: prevalence of
      mechanical syndromes and preferred loading strategies.
AB  - BACKGROUND: Classification of patients with extremity problems is commonly based
      on patho-anatomical diagnoses, but problems exist regarding reliability and
      validity of the tests and diagnostic criteria used. Alternatively, a
      classification system based on patient response to repeated loading strategies
      can be used to classify and direct management. OBJECTIVE: The purpose of this
      study was to investigate the prevalence of McKenzie's classification categories
      among patients with extremity problems and the loading strategies used in their
      management. DESIGN: This was a prospective, observational study. METHODS: Thirty
      therapists among 138 invited (response rate=22%) with a Diploma in Mechanical
      Diagnosis and Therapy (MDT) were identified from the McKenzie Institute
      International registry and recruited worldwide to complete an e-mailed
      questionnaire. They provided data about their age, years qualified, years since
      gaining a diploma, and practice, and prospectively provided data on anatomical
      site and categorization for 15 consecutive patients with extremity problems.
      RESULTS: Data were gathered on 388 patients; classification categories were as
      follows: derangement (37%); contractile dysfunction (17%); articular dysfunction
      (10%); and "other" (36%), of which 20% were postsurgery or posttrauma. Exercise
      management strategies and syndrome application varied considerably among
      anatomical sites. Classification categories remained consistent in 85.8% of
      patients over the treatment episode. LIMITATIONS: These findings are not
      generalizable to therapists who are not experienced with use of MDT in the
      extremities. CONCLUSIONS: This study demonstrates that trained clinicians can
      classify patients with extremity problems into MDT classifications and that these
      classifications remain stable during the treatment episode. Further work is
      needed to test the efficacy of this system compared with other approaches, but if
      derangements are as common as this survey suggests, the findings have important
      prognostic implications because this syndrome is defined by its rapid response to
      repeated movements.

PMID- 22628584
TI  - Instability of the shoulder following seizures.
AB  - Dislocation of the shoulder may occur during seizures in epileptics and other
      patients who have convulsions. Following the initial injury, recurrent
      instability is common owing to a tendency to develop large bony abnormalities of
      the humeral head and glenoid and a susceptibility to further seizures. Assessment
      is difficult and diagnosis may be missed, resulting in chronic locked
      dislocations with protracted morbidity. Many patients have medical comorbidities,
      and successful treatment requires a multidisciplinary approach addressing the
      underlying seizure disorder in addition to the shoulder pathology. The use of
      bony augmentation procedures may have improved the outcomes after surgical
      intervention, but currently there is no evidence-based consensus to guide
      treatment. This review outlines the epidemiology and pathoanatomy of seizure
      related instability, summarising the currently-favoured options for treatment,
      and their results.

PMID- 22628583
TI  - A cane improves postural recovery from an unpracticed slip during walking in
      people with Parkinson disease.
AB  - BACKGROUND: Little is known about the effects of use of a cane on balance during
      perturbed gait or whether people with Parkinson disease (PD) benefit from using a
      cane. OBJECTIVES: The purpose of this study was to evaluate the effects of cane
      use on postural recovery from a slip due to repeated surface perturbations in
      individuals with PD compared with age- and sex-matched individuals who were
      healthy. DESIGN: This was a prospective study with 2 groups of participants.
      METHODS: Fourteen individuals with PD (PD group) and 11 individuals without PD
      (control group) walked across a platform that translated 15 cm rightward at 30
      cm/s during the single-limb support phase of the right foot. Data from 15 trials
      in 2 conditions (ie, with and without an instrumented cane in the right hand)
      were collected in random order. Outcome measures included lateral displacement of
      body center of mass (COM) due to the slip and compensatory step width and length
      after the perturbation. RESULTS: Cane use improved postural recovery from the
      first untrained slip, characterized by smaller lateral COM displacement, in the
      PD group but not in the control group. The beneficial effect of cane use,
      however, occurred only during the first perturbation, and those individuals in
      the PD group who demonstrated the largest COM displacement without a cane
      benefited the most from use of a cane. Both PD and control groups gradually
      decreased lateral COM displacement across slip exposures, but a slower learning
      rate was evident in the PD group participants, who required 6, rather than 3,
      trials for adapting balance recovery. LIMITATIONS: Future studies are needed to
      examine the long-term effects of repeated slip training in people with PD.
      CONCLUSIONS: Use of a cane improved postural recovery from an unpracticed slip in
      individuals with PD. Balance in people with PD can be improved by training with
      repeated exposures to perturbations.

PMID- 22628585
TI  - Combined (mechanical and pharmacological) modalities for the prevention of venous
      thromboembolism in joint replacement surgery.
AB  - We performed a systematic review and meta-analysis to compare the efficacy of
      intermittent mechanical compression combined with pharmacological
      thromboprophylaxis, against either mechanical compression or pharmacological
      prophylaxis in preventing deep-vein thrombosis (DVT) and pulmonary embolism in
      patients undergoing hip or knee replacement. A total of six randomised controlled
      trials, evaluating a total of 1399 patients, were identified. In knee
      arthroplasty, the rate of DVT was reduced from 18.7% with anticoagulation alone
      to 3.7% with combined modalities (risk ratio (RR) 0.27, p = 0.03; number needed
      to treat: seven). There was moderate, albeit non-significant, heterogeneity (I(2)
      = 42%). In hip replacement, there was a non-significant reduction in DVT from
      8.7% with mechanical compression alone to 7.2% with additional pharmacological
      prophylaxis (RR 0.84) and a significant reduction in DVT from 9.7% with
      anticoagulation alone to 0.9% with additional mechanical compression (RR 0.17, p
      < 0.001; number needed to treat: 12), with no heterogeneity (I(2) = 0%). The
      included studies had insufficient power to demonstrate an effect on pulmonary
      embolism. We conclude that the addition of intermittent mechanical leg
      compression augments the efficacy of anticoagulation in preventing DVT in
      patients undergoing both knee and hip replacement. Further research on the role
      of combined modalities in thromboprophylaxis in joint replacement and in other
      high-risk situations, such as fracture of the hip, is warranted.

PMID- 22628586
TI  - Ceramic-on-ceramic bearings in hip arthroplasty: state of the art and the future.
AB  - This systematic review of the literature summarises the clinical experience with
      ceramic-on-ceramic hip bearings over the past 40 years and discusses the concerns
      that exist in relation to the bearing combination. Loosening, fracture, liner
      chipping on insertion, liner canting and dissociation, edge-loading and squeaking
      have all been reported, and the relationship between these issues and implant
      design and surgical technique is investigated. New design concepts are introduced
      and analysed with respect to previous clinical experience.

PMID- 22628587
TI  - Independent predictors of revision following metal-on-metal hip resurfacing: a
      retrospective cohort study using National Joint Registry data.
AB  - Modern metal-on-metal hip resurfacing has been widely performed in the United
      Kingdom for over a decade. However, the literature reports conflicting views of
      the benefits: excellent medium- to long-term results with some brands in specific
      subgroups, but high failure rates and local soft-tissue reactions in others. The
      National Joint Registry for England and Wales (NJR) has collected data on all hip
      resurfacings performed since 2003. This retrospective cohort study recorded
      survival time to revision from a resurfacing procedure, exploring risk factors
      independently associated with failure. All patients with a primary diagnosis of
      osteoarthritis who underwent resurfacing between 2003 and 2010 were included in
      the analyses. Cox's proportional hazard models were used to analyse the extent to
      which the risk of revision was related to patient, surgeon and implant
      covariates. A total of 27 971 hip resurfacings were performed during the study
      period, of which 1003 (3.59%) underwent revision surgery. In the final adjusted
      model, we found that women were at greater risk of revision than men (hazard
      ratio (HR) = 1.30, p = 0.007), but the risk of revision was independent of age.
      Of the implant-specific predictors, five brands had a significantly greater risk
      of revision than the Birmingham Hip Resurfacing (BHR) (ASR: HR = 2.82, p < 0.001,
      Conserve: HR = 2.03, p < 0.001, Cormet: HR = 1.43, p = 0.001, Durom: HR = 1.67, p
      < 0.001, Recap: HR = 1.58, p = 0.007). Smaller femoral head components were also
      significantly more likely to require revision (<= 44 mm: HR = 2.14, p < 0.001, 45
      to 47 mm: HR = 1.48, p = 0.001) than medium or large heads, as were operations
      performed by low-volume surgeons (HR = 1.36, p < 0.001). Once these influences
      had been removed, in 4873 male patients < 60 years old undergoing resurfacing
      with a BHR, the five-year estimated risk of revision was 1.59%. In summary, after
      adjustment for a range of covariates we found that there were significant
      differences in the rate of failure between brands and component sizes. Younger
      male patients had good five-year implant survival when the BHR was used.

PMID- 22628588
TI  - High incidence of pseudotumour formation after large-diameter metal-on-metal
      total hip replacement: a prospective cohort study.
AB  - Peri-articular soft-tissue masses or 'pseudotumours' can occur after large
      diameter metal-on-metal (MoM) resurfacing of the hip and conventional total hip
      replacement (THR). Our aim was to assess the incidence of pseudotumour formation
      and to identify risk factors for their formation in a prospective cohort study. A
      total of 119 patients who underwent 120 MoM THRs with large-diameter femoral
      heads between January 2005 and November 2007 were included in the study. Outcome
      scores, serum metal ion levels, radiographs and CT scans were obtained. Patients
      with symptoms or an identified pseudotumour were offered MRI and an ultrasound
      guided biopsy. There were 108 patients (109 hips) eligible for evaluation by CT
      scan at a mean follow-up of 3.6 years (2.5 to 4.5); 42 patients (39%) were
      diagnosed with a pseudotumour. The hips of 13 patients (12%) were revised to a
      polyethylene acetabular component with small-diameter metal head. Patients with
      elevated serum metal ion levels had a four times increased risk of developing a
      pseudotumour. This study shows a substantially higher incidence of pseudotumour
      formation and subsequent revisions in patients with MoM THRs than previously
      reported. Because most revision cases were identified only after an intensive
      screening protocol, we recommend close monitoring of patients with MoM THR.

PMID- 22628589
TI  - Segmental proximal femoral bone loss and revision total hip replacement in
      patients with developmental dysplasia of the hip: the role of allograft
      prosthesis composite.
AB  - The treatment of substantial proximal femoral bone loss in young patients with
      developmental dysplasia of the hip (DDH) is challenging. We retrospectively
      analysed the outcome of 28 patients (30 hips) with DDH who underwent revision
      total hip replacement (THR) in the presence of a deficient proximal femur, which
      was reconstructed with an allograft prosthetic composite. The mean follow-up was
      15 years (8.5 to 25.5). The mean number of previous THRs was three (1 to 8). The
      mean age at primary THR and at the index reconstruction was 41 years (18 to 61)
      and 58.1 years (32 to 72), respectively. The indication for revision included
      mechanical loosening in 24 hips, infection in three and peri-prosthetic fracture
      in three. Six patients required removal and replacement of the allograft
      prosthetic composite, five for mechanical loosening and one for infection. The
      survivorship at ten, 15 and 20 years was 93% (95% confidence interval (CI) 91 to
      100), 75.5% (95% CI 60 to 95) and 75.5% (95% CI 60 to 95), respectively, with 25,
      eight, and four patients at risk, respectively. Additionally, two junctional
      nonunions between the allograft and host femur required bone grafting and
      plating. An allograft prosthetic composite affords a good long-term outcome in
      the management of proximal femoral bone loss in revision THR in patients with
      DDH, while preserving distal host bone.

PMID- 22628590
TI  - Resurfacing arthroplasty for hip dysplasia: a prospective randomised study.
AB  - In this prospective study a total of 80 consecutive Chinese patients with Crowe
      type I or II developmental dysplasia of the hip were randomly assigned for hip
      resurfacing arthroplasty (HRA) or total hip replacement (THR). Three patients
      assigned to HRA were converted to THR, and three HRA patients and two THR
      patients were lost to follow-up. This left a total of 34 patients (37 hips) who
      underwent HRA and 38 (39 hips) who underwent THR. The mean follow-up was 59.4
      months (52 to 70) in the HRA group and 60.6 months (50 to 72) in the THR group.
      There was no failure of the prosthesis in either group. Flexion of the hip was
      significantly better after HRA, but there was no difference in the mean post
      operative Harris hip scores between the groups. The mean size of the acetabular
      component in the HRA group was significantly larger than in the THR group (49.5
      mm vs 46.1 mm, p = 0.001). There was no difference in the mean abduction angle of
      the acetabular component between the two groups. Although the patients in this
      series had risk factors for failure after HRA, such as low body weight, small
      femoral heads and dysplasia, the clinical results of resurfacing in those with
      Crowe type I or II hip dysplasia were satisfactory. Patients in the HRA group had
      a better range of movement, although neck-cup impingement was observed. However,
      more acetabular bone was sacrificed in HRA patients, and it is unclear whether
      this will have an adverse effect in the long term.

PMID- 22628591
TI  - A comparison of a conventional versus a short, anatomical metaphyseal-fitting
      cementless femoral stem in the treatment of patients with a fracture of the
      femoral neck.
AB  - We compared the clinical and radiological outcomes of two cementless femoral
      stems in the treatment of patients with a Garden III or IV fracture of the
      femoral neck. A total of 70 patients (70 hips) in each group were enrolled into a
      prospective randomised study. One group received a short anatomical cementless
      stem and the other received a conventional cementless stem. Their mean age was
      74.9 years (50 to 94) and 76.0 years (55 to 96), respectively (p = 0.328). The
      mean follow-up was 4.1 years (2 to 5) and 4.8 years (2 to 6), respectively.
      Perfusion lung scans and high resolution chest CTs were performed to detect
      pulmonary microemboli. At final follow-up there were no statistically significant
      differences between the short anatomical and the conventional stems with regard
      to the mean Harris hip score (85.7 (66 to 100) versus 86.5 (55 to 100); p =
      0.791), the mean Western Ontario and McMaster Universities Osteoarthritis Index
      (17 (6 to 34) versus 16 (5 to 35); p = 0.13) or the mean University of
      California, Los Angeles activity score (5 (3 to 6) versus 4 (3 to 6); p = 0.032).
      No patient with a short stem had thigh pain, but 11 patients (16%) with a
      conventional stem had thigh pain. No patients with a short stem had symptomatic
      pulmonary microemboli, but 11 patients with a conventional stem had pulmonary
      microemboli (symptomatic in three patients and asymptomatic in eight patients).
      One hip (1.4%) in the short stem group and eight (11.4%) in the conventional
      group had an intra-operative undisplaced fracture of the calcar. No component was
      revised for aseptic loosening in either group. One acetabular component in the
      short stem group and two acetabular components in the conventional stem group
      were revised for recurrent dislocation. Our study demonstrated that despite the
      poor bone quality in these elderly patients with a fracture of the femoral neck,
      osseo-integration was obtained in all hips in both groups. However, the incidence
      of thigh pain, pulmonary microemboli and peri-prosthetic fracture was
      significantly higher in the conventional stem group than in the short stem group.

PMID- 22628592
TI  - Balance is an important predictive factor for quality of life and function after
      primary total knee replacement.
AB  - We investigated the extent to which improved balance relative to pain relief
      correlates with the success of total knee replacement (TKR). A total of 81
      patients were recruited to the study: 16 men (19.8%) and 65 women (80.2%). Of
      these, 62 patients (10 men, 52 women) with a mean age of 73 (57 to 83) underwent
      static and dynamic assessment of balance pre-operatively and one year post
      operatively. The parameters of balance were quantified using commercially
      available and validated equipment. Motor function and self-reported outcome were
      also assessed. There was a significant improvement in dynamic balance (p < 0.001)
      one year after TKR, and better balance correlated with improved mobility,
      functional balance and increased health-related quality of life. As it seems that
      balance, and not only pain relief, influences the success of TKR, balance skills
      should be better addressed during the post-operative rehabilitation of patients
      who undergo TKR.

PMID- 22628593
TI  - Do we need a gender-specific total knee replacement? A randomised controlled
      trial comparing a high-flex and a gender-specific posterior design.
AB  - The purpose of this study was to investigate whether a gender-specific high
      flexion posterior-stabilised (PS) total knee replacement (TKR) would offer
      advantages over a high-flex PS TKR regarding range of movement (ROM), 'feel' of
      the knee, pain and satisfaction, as well as during activity. A total of 24 female
      patients with bilateral osteoarthritis entered this prospective, blind randomised
      trial in which they received a high-flex PS TKR in one knee and a gender-specific
      high-flexion PS TKR in the other knee. At follow-up, patients were assessed
      clinically measuring ROM, and questioned about pain, satisfaction and daily
      'feel' of each knee. Patients underwent gait analysis pre-operatively and at one
      year, which yielded kinematic, kinetic and temporospatial parameters indicative
      of knee function during gait. At final follow-up we found no statistically
      significant differences in ROM (p = 0.82). The median pain score was 0 (0 to 8)
      in both groups (p = 0.95). The median satisfaction score was 9 (4 to 10) in the
      high-flex group and 8 (0 to 10) in the gender-specific group (p = 0.98). The
      median 'feel' score was 9 (3 to 10) in the high-flex group and 8 (0 to 10) in the
      gender-specific group (p = 0.66). Gait analysis showed no statistically
      significant differences between the two prosthetic designs in any kinematic,
      kinetic or temporospatial parameters. Both designs produced good clinical results
      with significant improvements in several gait parameters without evidence of any
      advantage in the gender-specific design.

PMID- 22628594
TI  - The Bologna-Oxford total ankle replacement: a mid-term follow-up study.
AB  - The Bologna-Oxford (BOX) total ankle replacement (TAR) was developed with the aim
      of achieving satisfactory pain-free movement of the ankle. To date, only one
      single multicentre study has reported its clinical results. The aim of this study
      was to conduct an independent review of its mid-term results. We retrospectively
      reviewed a total of 60 prospectively followed patients in whom 62 BOX TARs had
      been implanted between 2004 and 2008. We used the American Orthopedic Foot and
      Ankle Society (AOFAS) score to assess the clinical results. Standardised
      radiographs taken at the time of final follow-up were analysed by two observers.
      The overall survival was 91.9% at a mean follow-up of 42.5 months (24 to 71). The
      mean AOFAS score had improved from 35.1 points (sd 16.6; 4 to 73) pre-operatively
      to 78.0 (sd 10.7; 57 to 100) at final follow-up (p < 0.01). Tibial radiolucencies
      < 2 mm in width were seen around 16 TARs. Talar radiolucencies < 2 mm were seen
      around four TARs. A total of 47 patients (78.3%) were very satisfied or satisfied
      with the outcome. Five patients required revision for functional limitation or
      continuing pain.

PMID- 22628595
TI  - Injuries of the terminal branches of the infraclavicular brachial plexus:
      patterns of injury, management and outcome.
AB  - We reviewed 101 patients with injuries of the terminal branches of the
      infraclavicular brachial plexus sustained between 1997 and 2009. Four patterns of
      injury were identified: 1) anterior glenohumeral dislocation (n = 55), in which
      the axillary and ulnar nerves were most commonly injured, but the axillary nerve
      was ruptured in only two patients (3.6%); 2) axillary nerve injury, with or
      without injury to other nerves, in the absence of dislocation of the shoulder (n
      = 20): these had a similar pattern of nerve involvement to those with a known
      dislocation, but the axillary nerve was ruptured in 14 patients (70%); 3)
      displaced proximal humeral fracture (n = 15), in which nerve injury resulted from
      medial displacement of the humeral shaft: the fracture was surgically reduced in
      13 patients; and 4) hyperextension of the arm (n = 11): these were characterised
      by disruption of the musculocutaneous nerve. There was variable involvement of
      the median and radial nerves with the ulnar nerve being least affected. Surgical
      intervention is not needed in most cases of infraclavicular injury associated
      with dislocation of the shoulder. Early exploration of the nerves should be
      considered in patients with an axillary nerve palsy without dislocation of the
      shoulder and for musculocutaneous nerve palsy with median and/or radial nerve
      palsy. Urgent operation is needed in cases of nerve injury resulting from
      fracture of the humeral neck to relieve pressure on nerves.

PMID- 22628596
TI  - Short- to mid-term results of metallic press-fit radial head arthroplasty in
      unstable injuries of the elbow.
AB  - We assessed the short- to mid-term survival of metallic press-fit radial head
      prostheses in patients with radial head fractures and acute traumatic instability
      of the elbow. The medical records of 42 patients (16 males, 26 females) with a
      mean age of 56 years (23 to 85) with acute unstable elbow injuries, including a
      fracture of the radial head requiring metallic replacement of the radial head,
      were reviewed retrospectively. Survival of the prosthesis was assessed from the
      radiographs of 37 patients after a mean follow-up of 50 months (12 to 107). The
      functional results of 31 patients were assessed using range-of-movement, Mayo
      elbow performance score (MEPS), Disabilities of the Arm, Shoulder and Hand (DASH)
      score and the RAND 36-item health survey. At the most recent follow-up 25
      prostheses were still well fixed, nine had been removed because of loosening, and
      three remained implanted but were loose. The mean time from implantation to
      loosening was 11 months (2 to 24). Radiolucent lines that developed around the
      prosthesis before removal were mild in three patients, moderate in one and severe
      in five. Range of movement parameters and mass grip strength were significantly
      lower in the affected elbow than in the unaffected side. The mean MEPS score was
      86 (40 to 100) and the mean DASH score was 23 (0 to 81). According to RAND-36
      scores, patients had more pain and lower physical function scores than normal
      population values. Loosening of press-fit radial head prostheses is common,
      occurs early, often leads to severe osteolysis of the proximal radius, and
      commonly requires removal of the prosthesis.

PMID- 22628597
TI  - The outcome of carpal tunnel decompression in patients with diabetes mellitus.
AB  - Diabetes mellitus is recognised as a risk factor for carpal tunnel syndrome. The
      response to treatment is unclear, and may be poorer than in non-diabetic
      patients. Previous randomised studies of interventions for carpal tunnel syndrome
      have specifically excluded diabetic patients. The aim of this study was to
      investigate the epidemiology of carpal tunnel syndrome in diabetic patients, and
      compare the outcome of carpal tunnel decompression with non-diabetic patients.
      The primary endpoint was improvement in the QuickDASH score. The prevalence of
      diabetes mellitus was 11.3% (176 of 1564). Diabetic patients were more likely to
      have severe neurophysiological findings at presentation. Patients with diabetes
      had poorer QuickDASH scores at one year post-operatively (p = 0.028), although
      the mean difference was lower than the minimal clinically important difference
      for this score. After controlling for underlying differences in age and gender,
      there was no difference between groups in the magnitude of improvement after
      decompression (p = 0.481). Patients with diabetes mellitus can therefore be
      expected to enjoy a similar improvement in function.

PMID- 22628598
TI  - Percutaneous vertebroplasty for subacute and chronic painful osteoporotic
      vertebral compression fractures can safely be undertaken in the first year after
      the onset of symptoms.
AB  - The optimal timing of percutaneous vertebroplasty as treatment for painful
      osteoporotic vertebral compression fractures (OVCFs) is still unclear. With the
      position of vertebroplasty having been challenged by recent placebo-controlled
      studies, appropriate timing gains importance. We investigated the relationship
      between the onset of symptoms - the time from fracture - and the efficacy of
      vertebroplasty in 115 patients with 216 painful subacute or chronic OVCFs (mean
      time from fracture 6.0 months (sd 2.9)). These patients were followed
      prospectively in the first post-operative year to assess the level of back pain
      and by means of health-related quality of life (HRQoL). We also investigated
      whether greater time from fracture resulted in a higher risk of complications or
      worse pre-operative condition, increased vertebral deformity or the development
      of nonunion of the fracture as demonstrated by the presence of an intravertebral
      cleft. It was found that there was an immediate and sustainable improvement in
      the level of back pain and HRQoL after vertebroplasty, which was independent of
      the time from fracture. Greater time from fracture was associated with neither
      worse pre-operative conditions nor increased vertebral deformity, nor with the
      presence of an intravertebral cleft. We conclude that vertebroplasty can be
      safely undertaken at an appropriate moment between two and 12 months following
      the onset of symptoms of an OVCF.

PMID- 22628599
TI  - The surgical treatment of pyogenic spondylitis using posterior instrumentation
      without anterior debridement.
AB  - There have been few reports regarding the efficacy of posterior instrumentation
      alone as surgical treatment for patients with pyogenic spondylitis, thus avoiding
      the morbidity of anterior surgery. We report the clinical outcomes of six
      patients with pyogenic spondylitis treated effectively with a single-stage
      posterior fusion without anterior debridement at a mean follow-up of 2.8 years (2
      to 5). Haematological data, including white cell count and level of C-reactive
      protein, returned to normal in all patients at a mean of 8.2 weeks (7 to 9) after
      the posterior fusion. Rigid bony fusion between the infected vertebrae was
      observed in five patients at a mean of 6.3 months (4.5 to 8) post-operatively,
      with the remaining patient having partial union. Severe back pain was immediately
      reduced following surgery and the activities of daily living showed a marked
      improvement. Methicillin-resistant Staphylococcus aureus was detected as the
      causative organism in four patients. Single-stage posterior fusion may be
      effective in patients with pyogenic spondylitis who have relatively minor bony
      destruction.

PMID- 22628600
TI  - Gemella haemolysans spondylodiscitis: a report of two cases.
AB  - We report on two cases of infective spondylodiscitis caused by Gemella
      haemolysans in otherwise healthy patients. This organism has only rarely been
      identified as a cause of bone and joint infection, with only two previous reports
      of infective spondylodiscitis. We describe the clinical features, investigations
      and treatment options.

PMID- 22628601
TI  - The open blast pelvis: the significant burden of management.
AB  - The open blast fracture of the pelvis is considered to be the most severe injury
      within the spectrum of battlefield trauma. We report our experience of 29
      consecutive patients who had sustained this injury in Afghanistan between 2008
      and 2010. Their median new injury severity score (NISS) was 41 (8 to 75), and
      mean blood requirement in the first 24 hours was 60.3 units (0 to 224). In
      addition to their orthopaedic injury, six had an associated vascular injury,
      seven had a bowel injury, 11 had a genital injury and seven had a bladder injury.
      In all, eight fractures were managed definitively with external fixation and
      seven required internal fixation. Of those patients who underwent internal
      fixation, four required removal of metalwork for infection. Faecal diversion was
      performed in nine cases. The median length of hospital stay following emergency
      repatriation to the United Kingdom was 70.5 days (5 to 357) and the mean total
      operating time was 29.6 hours (5 to 187). At a mean follow-up of 20.3 months
      (13.2 to 29.9), 24 patients (82.8%) were able to walk and 26 (89.7%) had clinical
      and radiological evidence of stability of the pelvic ring. As a result of the
      increase in terrorism, injuries that were previously confined exclusively to
      warfare can now occur anywhere, with civilian surgeons who are involved in trauma
      care potentially required to manage similar injuries. Our study demonstrates that
      the management of this injury pattern demands huge resources and significant
      multidisciplinary input. Given the nature of the soft-tissue injury, we would
      advocate external fixation as the preferred management of these fractures. With
      the advent of emerging wound and faecal management techniques, we do not believe
      that faecal diversion is necessary in all cases.

PMID- 22628602
TI  - Factors affecting outcome of massive intercalary bone allografts in the treatment
      of tumours of the femur.
AB  - We retrospectively reviewed 101 consecutive patients with 114 femoral tumours
      treated by massive bone allograft at our institution between 1986 and 2005. There
      were 49 females and 52 males with a mean age of 20 years (4 to 74). At a median
      follow-up of 9.3 years (2 to 19.8), 36 reconstructions (31.5%) had failed. The
      allograft itself failed in 27 reconstructions (24%). Mechanical complications
      such as delayed union, fracture and failure of fixation were studied. The most
      adverse factor on the outcome was the use of intramedullary nails, followed by
      post-operative chemotherapy, resection length > 17 cm and age > 18 years at the
      time of intervention. The simultaneous use of a vascularised fibular graft to
      protect the allograft from mechanical complications improved the outcome, but the
      use of intramedullary cementing was not as successful. In order to improve the
      strength of the reconstruction and to advance the biology of host-graft
      integration, we suggest avoiding the use of intramedullary nails and titanium
      plates, but instead using stainless steel plates, as these gave better results.
      The use of a supplementary vascularised fibular graft should be strongly
      considered in adult patients with resection > 17 cm and in those who require post
      operative chemotherapy.

PMID- 22628603
TI  - Arthroscopic reduction of the dislocated hip in infants.
AB  - We present our early experience of arthroscopic reduction of the dislocated hip
      in very young infants with developmental dysplasia of the hip (DDH). Eight
      dislocated hips, which had failed attempts at closed reduction, were treated by
      arthroscopy of the hip in five children with a mean age of 5.8 months (4 to 7). A
      two-portal technique was used, with a medial sub-adductor portal for a 2.7 mm
      cannulated system with a 70 degrees  arthroscope and an anterolateral portal for
      the instruments. Following evaluation of the key intra-articular structures, the
      hypertrophic ligamentum teres and acetabular pulvinar were resected, and a
      limited release of the capsule was performed prior to reduction of the hip. All
      hips were reduced by a single arthroscopic procedure, the reduction being
      confirmed on MRI scan. None of the hips had an inverted labrum. The greatest
      obstacle to reduction was a constriction of the capsule. At a mean follow-up of
      13.2 months (9 to 24), all eight hips remained stable. Three developed avascular
      necrosis. The mean acetabular index decreased from 35.5 degrees  (30 degrees  to
      40 degrees ) pre-operatively to 23.3 degrees  (17 degrees  to 28 degrees ). This
      study demonstrates that arthroscopic reduction is feasible using two standardised
      portals. Longer follow-up studies are necessary to evaluate the functional
      results.

PMID- 22628604
TI  - Translational hurdles for tissue engineering: an in vitro analysis of commonly
      used local anaesthetics on skeletal stem cell survival.
AB  - When transferring tissue regenerative strategies involving skeletal stem cells to
      human application, consideration needs to be given to factors that may affect the
      function of the cells that are transferred. Local anaesthetics are frequently
      used during surgical procedures, either administered directly into the operative
      site or infiltrated subcutaneously around the wound. The aim of this study was to
      investigate the effects of commonly used local anaesthetics on the morphology,
      function and survival of human adult skeletal stem cells. Cells from three
      patients who were undergoing elective hip replacement were harvested and
      incubated for two hours with 1% lidocaine, 0.5% levobupivacaine or 0.5%
      bupivacaine hydrochloride solutions. Viability was quantified using WST-1 and DNA
      assays. Viability and morphology were further characterised using CellTracker
      Green/Ethidium Homodimer-1 immunocytochemistry and function was assessed by an
      alkaline phosphatase assay. An additional group was cultured for a further seven
      days to allow potential recovery of the cells after removal of the local
      anaesthetic. A statistically significant and dose dependent reduction in cell
      viability and number was observed in the cell cultures exposed to all three local
      anaesthetics at concentrations of 25% and 50%, and this was maintained even
      following culture for a further seven days. This study indicates that certain
      local anaesthetic agents in widespread clinical use are deleterious to skeletal
      progenitor cells when studied in vitro; this might have relevance in clinical
      applications.

PMID- 22628605
TI  - A comparison of lidocaine, ropivacaine and dexamethasone toxicity on bovine
      tenocytes in culture.
AB  - Peri-tendinous injection of local anaesthetic, both alone and in combination with
      corticosteroids, is commonly performed in the treatment of tendinopathies.
      Previous studies have shown that local anaesthetics and corticosteroids are
      chondrotoxic, but their effect on tenocytes remains unknown. We compared the
      effects of lidocaine and ropivacaine, alone or combined with dexamethasone, on
      the viability of cultured bovine tenocytes. Tenocytes were exposed to ten
      different conditions: 1) normal saline; 2) 1% lidocaine; 3) 2% lidocaine; 4) 0.2%
      ropivacaine; 5) 0.5% ropivacaine; 6) dexamethasone (dex); 7) 1% lidocaine+dex; 8)
      2% lidocaine+dex; 9) 0.2% ropivacaine+dex; and 10) 0.5% ropivacaine+dex, for 30
      minutes. After a 24-hour recovery period, the viability of the tenocytes was
      quantified using the CellTiter-Glo viability assay and fluorescence-activated
      cell sorting (FACS) for live/dead cell counts. A 30-minute exposure to lidocaine
      alone was significantly toxic to the tenocytes in a dose-dependent manner, but a
      30-minute exposure to ropivacaine or dexamethasone alone was not significantly
      toxic. Dexamethasone potentiated ropivacaine tenocyte toxicity at higher doses of
      ropivacaine, but did not potentiate lidocaine tenocyte toxicity. As seen in other
      cell types, lidocaine has a dose-dependent toxicity to tenocytes but ropivacaine
      is not significantly toxic. Although dexamethasone alone is not toxic, its
      combination with 0.5% ropivacaine significantly increased its toxicity to
      tenocytes. These findings might be relevant to clinical practice and warrant
      further investigation.

PMID- 22628606
TI  - Exam corner - June 2012.
AB  - The FRCS (Tr & Orth) examination has three components: MCQs, Vivas and Clinical
      Examination. The Vivas are further divided into four sections comprising Basic
      Science, Adult Pathology, Hands and Children's Orthopaedics and Trauma. The
      Clinical Examination section is divided into Upper and Lower limb cases. The aim
      of this section in the Journal is to focus specifically on the trainees preparing
      for the exam and to cater to all the sections of the exam. The vision is to
      complete the cycle of all relevant exam topics (as per the syllabus) in four
      years.

PMID- 22628607
TI  - A novel point mutation in the KCNJ5 gene causing primary hyperaldosteronism and
      early-onset autosomal dominant hypertension.
AB  - CONTEXT: Aldosterone production in the adrenal zona glomerulosa is mainly
      regulated by angiotensin II, [K(+)], and ACTH. Genetic deletion of subunits of
      K(+)-selective leak (KCNK) channels TWIK-related acid sensitive K(+)-1 and/or
      TWIK-related acid sensitive K(+)-3 in mice results in primary hyperaldosteronism,
      whereas mutations in the KCNJ5 (potassium inwardly rectifying channel, subfamily
      J, member 5) gene are implicated in primary hyperaldosteronism and, in certain
      cases, in autonomous glomerulosa cell proliferation in humans. OBJECTIVE: The
      objective of the study was to investigate the role of KCNK3, KCNK5, KCNK9, and
      KCNJ5 genes in a family with primary hyperaldosteronism and early-onset
      hypertension. PATIENTS AND METHODS: Two patients, a mother and a daughter,
      presented with severe primary hyperaldosteronism, bilateral massive adrenal
      hyperplasia, and early-onset hypertension refractory to medical treatment.
      Genomic DNA was isolated and the exons of the entire coding regions of the above
      genes were amplified and sequenced. Electrophysiological studies were performed
      to determine the effect of identified mutation(s) on the membrane reversal
      potentials. RESULTS: Sequencing of the KCNJ5 gene revealed a single, heterozygous
      guanine to thymine (G -> T) substitution at nucleotide position 470 (n.G470T),
      resulting in isoleucine (I) to serine (S) substitution at amino acid 157
      (p.I157S). This mutation results in loss of ion selectivity, cell membrane
      depolarization, increased Ca(2+) entry in adrenal glomerulosa cells, and
      increased aldosterone synthesis. Sequencing of the KCNK3, KCNK5, and KCNK9 genes
      revealed no mutations in our patients. CONCLUSIONS: These findings explain the
      pathogenesis in a subset of patients with severe hypertension and implicate loss
      of K(+) channel selectivity in constitutive aldosterone production.

PMID- 22628608
TI  - Effect of KCNJ5 mutations on gene expression in aldosterone-producing adenomas
      and adrenocortical cells.
AB  - CONTEXT: Primary aldosteronism is a heterogeneous disease that includes both
      sporadic and familial forms. A point mutation in the KCNJ5 gene is responsible
      for familial hyperaldosteronism type III. Somatic mutations in KCNJ5 also occur
      in sporadic aldosterone producing adenomas (APA). OBJECTIVE: The objective of the
      study was to define the effect of the KCNJ5 mutations on gene expression and
      aldosterone production using APA tissue and human adrenocortical cells. METHODS:
      A microarray analysis was used to compare the transcriptome profiles of female
      derived APA samples with and without KCNJ5 mutations and HAC15 adrenal cells
      overexpressing either mutated or wild-type KCNJ5. Real-time PCR validated a set
      of differentially expressed genes. Immunohistochemical staining localized the
      KCNJ5 expression in normal adrenals and APA. RESULTS: We report a 38% (18 of 47)
      prevalence of KCNJ5 mutations in APA. KCNJ5 immunostaining was highest in the
      zona glomerulosa of NA and heterogeneous in APA tissue, and KCNJ5 mRNA was 4-fold
      higher in APA compared with normal adrenals (P < 0.05). APA with and without
      KCNJ5 mutations displayed slightly different gene expression patterns, notably
      the aldosterone synthase gene (CYP11B2) was more highly expressed in APA with
      KCNJ5 mutations. Overexpression of KCNJ5 mutations in HAC15 increased aldosterone
      production and altered expression of 36 genes by greater than 2.5-fold (P <
      0.05). Real-time PCR confirmed increases in CYP11B2 and its transcriptional
      regulator, NR4A2. CONCLUSIONS: KCNJ5 mutations are prevalent in APA, and our data
      suggest that these mutations increase expression of CYP11B2 and NR4A2, thus
      increasing aldosterone production.

PMID- 22628609
TI  - Palliative surgery for acetabular metastasis with pathological central
      dislocation of the hip joint after radiation therapy: a case report.
AB  - Orthopedic surgery for bone metastases is mainly a palliative treatment.
      Pathological central dislocation of the hip joint secondary to osteonecrosis of
      acetabular metastasis after radiation therapy brings severe suffering to cancer
      patients. We performed minimally invasive palliative surgery for an elderly
      woman, and excellent pain relief was achieved. An 80-year-old female suffering
      from right hip pain was referred to our hospital. She had undergone surgery for
      lung cancer 5 years previously and her right acetabulum was subsequently affected
      by metastasis. With the aim of controlling the metastasis, radiation therapy was
      performed. Two years later, pathological central dislocation of the hip joint
      occurred with sudden onset of severe pain, and she was unable to maintain a
      sitting position and became bedridden. After she was referred to our hospital, we
      created an intentional pseudarthrosis in the femoral neck for palliation. After
      the surgery, excellent pain relief and remarkably improved mobility were achieved
      during her limited remaining lifetime. In this report, we introduce a novel
      method of producing a pseudarthrosis in the femoral neck for pathological
      dislocation. This procedure is a minimally invasive treatment and an alternative
      option for palliative surgery for pathological dislocation of the hip joint due
      to osteonecrosis after radiation therapy.

PMID- 22628610
TI  - Bortezomib-induced pneumonitis during bortezomib retreatment in multiple myeloma.
AB  - Bortezomib is a proteasome inhibitor and is active against multiple myeloma. Most
      toxicities associated with bortezomib are mild to moderate and manageable;
      however, bortezomib-induced pneumonitis has been reported in some multiple
      myeloma cases. Bortezomib-induced pneumonitis was reported to occur relatively
      soon after the first administration of bortezomib. A 64-year-old Japanese man
      with multiple myeloma received low-dose dexamethasone followed by bortezomib
      monotherapy as the initial therapy. He had no pulmonary complications during
      bortezomib treatment. Thereafter, he was treated with high-dose chemotherapy,
      followed by autologous peripheral blood stem cell transplantation. Ten months
      after autologous peripheral blood stem cell transplantation, his disease relapsed
      and he received bortezomib retreatment. On the fifth day after the second dose of
      weekly bortezomib, he complained of mild dyspnea, dry cough and fever. High
      resolution computed tomography of the chest showed bilateral infiltrates with
      partial ground glass appearance in the lower lobes. The diagnosis of bortezomib
      induced pneumonitis was made. His bortezomib-induced pneumonitis responded to
      steroid therapy and his respiratory symptoms disappeared. This is the first
      report in which bortezomib-induced pneumonitis occurred during bortezomib
      retreatment for relapsed multiple myeloma. Careful management is needed during
      bortezomib retreatment, even after the previous course of bortezomib was
      administered safely.

PMID- 22628611
TI  - The activity of the Bone and Soft Tissue Tumor Study Group of the Japan Clinical
      Oncology Group.
AB  - The Bone and Soft Tissue Tumor Study Group (BSTTSG) of the Japan Clinical
      Oncology Group (JCOG) was established in 2002. At present, 26 institutions are
      participating as active members of the BSTTSG of the JCOG. In 2004, the first
      BSTTSG trial, JCOG 0304, was initiated. JCOG 0304 was a Phase II study of
      perioperative chemotherapy with doxorubicin and ifosfamide for patients with
      operable, high-grade, non-round cell soft tissue sarcomas (T2bN0M0) arising in
      the extremities. The results of JCOG 0304 suggested the efficacy of the
      perioperative chemotherapy on operable soft tissue sarcoma in the extremities and
      led to planning of the subsequent clinical trial for the disease. The BSTTSG has
      currently been conducting a Phase III trial, JCOG 0905, to investigate the
      superiority of the addition of ifosfamide to the standard chemotherapy with
      methotrexate, cisplatin and doxorubicin for operable, high-grade osteosarcoma.
      The BSTTSG is also conducting a JCOG ancillary study, JCOG 0905-A1, to evaluate
      the gene expression profiles of osteosarcoma treated in the JCOG 0905 study. The
      BSTTSG will further try to develop new standard therapy for bone and soft tissue
      tumors.

PMID- 22628612
TI  - Thyroid dysfunction in patients treated with tyrosine kinase inhibitors,
      sunitinib, sorafenib and axitinib, for metastatic renal cell carcinoma.
AB  - OBJECTIVE: Targeted drugs are generally associated with a lower toxicity than
      conventional systemic cytotoxic drugs and, thus, are administered for long
      periods. As a result, unusual adverse effects, including thyroid dysfunction,
      have become important clinical issues. METHODS: We retrospectively collected the
      data and compared the incidence and the time of onset of thyroid dysfunction in
      33 patients (M/F: 26/7, age: 34-77) with metastatic renal cell carcinoma treated
      with the small-molecule tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib
      and axitinib in Yamagata University Hospital, Japan, from 2005 to 2010. RESULTS:
      The incidence of thyroid dysfunction tended to be higher in patients treated with
      axitinib (6 of 6: 100%) than in those treated with sunitinib (9 of 15: 60%) or
      sorafenib (6 of 12: 50%) (P= 0.1113). The median thyroid dysfunction-free
      survival evaluated using the Kaplan-Meier product-limit method with the log-rank
      test was significantly shorter in patients treated with axitinib than in those
      treated with sunitinib/sorafenib (3 vs. 16 weeks, P=0.0198). A multivariate Cox
      regression model for thyroid dysfunction-free survival with several probable
      confounding factors as co-variables showed that patients treated with axitinib
      were more likely to have thyroid dysfunction than the others (hazard ratio: 4.53,
      95% confidence interval: 1.40-14.63, P=0.0116). CONCLUSIONS: Patients treated
      with the tyrosine kinase inhibitors developed thyroid dysfunction frequently.
      Furthermore, those treated with axitinib developed thyroid dysfunction
      significantly more and at a faster rate than the others. Therefore, when the
      tyrosine kinase inhibitors, especially axitinib, are used, close monitoring of
      thyroid function is recommended, at least for the initial 1-2 months, to avoid
      clinical symptoms derived from thyroid dysfunction.

PMID- 22628613
TI  - Diacylglycerol acyl transferase 1 overexpression detoxifies cardiac lipids in
      PPARgamma transgenic mice.
AB  - Accumulation of excess lipids is associated with heart failure. The effects of
      transgenic expression of diacylglycerol acyl transferase 1 (DGAT1) in
      cardiomyocytes is controversial. We explored whether mice expressing DGAT1 via
      the myosin heavy chain (MHC) promoter develop heart dysfunction with aging or
      after crossing with mice over expressing peroxisome proliferator-activated
      receptor gamma (PPARgamma) in the heart. MHC-DGAT1 transgenic mice had increased
      heart triglyceride but no evidence of heart dysfunction, even up to age 12
      months. The MHC-DGAT1 transgene improved heart dysfunction and survival of MHC
      PPARgamma-expressing transgenic mice. Both diacylglycerol and ceramide levels in
      the heart were reduced by this cross, as were the levels of several mRNAs of
      genes involved in lipid metabolism. There were fewer large lipid droplets in MHC
      DGAT1*MHC-PPARgamma mice compared with MHC-PPARgamma, but total lipid content was
      not changed. Therefore, overexpression of DGAT1 is not toxic to the heart but
      reduces levels of toxic lipids and improves lipotoxic cardiomyopathy. Moreover,
      the beneficial effects of DGAT1 illustrate the interrelationship of several lipid
      metabolic pathways and the difficulty of assigning benefit to an isolated change
      in one potentially toxic lipid species.

PMID- 22628614
TI  - Glycosylphosphatidylinositol anchors regulate glycosphingolipid levels.
AB  - Glycosylphosphatidylinositol (GPI) anchor biosynthesis takes place in the
      endoplasmic reticulum (ER). After protein attachment, the GPI anchor is
      transported to the Golgi where it undergoes fatty acid remodeling. The ER exit of
      GPI-anchored proteins is controlled by glycan remodeling and p24 complexes act as
      cargo receptors for GPI anchor sorting into COPII vesicles. In this study, we
      have characterized the lipid profile of mammalian cell lines that have a defect
      in GPI anchor biosynthesis. Depending on which step of GPI anchor biosynthesis
      the cells were defective, we observed sphingolipid changes predominantly for very
      long chain monoglycosylated ceramides (HexCer). We found that the structure of
      the GPI anchor plays an important role in the control of HexCer levels. GPI
      anchor-deficient cells that generate short truncated GPI anchor intermediates
      showed a decrease in very long chain HexCer levels. Cells that synthesize GPI
      anchors but have a defect in GPI anchor remodeling in the ER have a general
      increase in HexCer levels. GPI-transamidase-deficient cells that produce no GPI
      anchored proteins but generate complete free GPI anchors had unchanged levels of
      HexCer. In contrast, sphingomyelin levels were mostly unaffected. We therefore
      propose a model in which the transport of very long chain ceramide from the ER to
      Golgi is regulated by the transport of GPI anchor molecules.

PMID- 22628615
TI  - Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high
      dose n3-HUFA in healthy volunteers.
AB  - A subject's baseline FA composition may influence the ability of dietary highly
      unsaturated omega-3 FAs (n3-HUFA) to change circulating profiles of esterified
      FAs and their oxygenated metabolites. This study evaluates the influence of basal
      n3-HUFA and n3-oxylipin status on the magnitude of response to n3-HUFA
      consumption. Blood was collected from fasting subjects (n = 30) before and after
      treatment (4 weeks; 11 +/- 2 mg/kg/day n3-HUFA ethyl esters). Esterified FAs were
      quantified in erythrocytes, platelets, and plasma by GC-MS. Esterified oxylipins
      were quantified in plasma by LC-MS/MS. Treatment with n3-HUFAs increased n3-HUFAs
      and decreased n6-HUFAs in all reservoirs and increased plasma n3-oxylipins
      without significantly changing n6-oxylipin concentrations. As subject basal n3
      HUFAs increased, treatment-associated changes decreased, and this behavior was
      reflected in the percentage of 20:5n3 + 22:6n3 in red blood cell membrane FAs
      (i.e., the omega-3 index). To maintain an omega-3 index of 8% and thus reduce
      cardiovascular disease risk, our analyses suggest a maintenance dose of 7
      mg/kg/day n3-HUFA ethyl esters for a 70-kg individual. These results suggest that
      the basal n3 index may have clinical utility to establish efficacious therapeutic
      experimental feeding regimens and to evaluate the USDA Dietary Guidelines
      recommendations for n3-HUFA consumption.

PMID- 22628616
TI  - Acute impact of apheresis on oxidized phospholipids in patients with familial
      hypercholesterolemia.
AB  - We measured oxidized phospholipids (OxPL), lipoprotein (a) [Lp(a)], and
      lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) pre- and postapheresis in
      18 patients with familial hypercholesterolemia (FH) and with low(~10 mg/dl; range
      10-11 mg/dl), intermediate (~50 mg/dl; range 30-61 mg/dl), or high (>100 mg/dl;
      range 78-128 mg/dl) Lp(a) levels. By using enzymatic and immunoassays, the
      content of OxPL and Lp-PLA(2) mass and activity were quantitated in lipoprotein
      density fractions plated in microtiter wells, as well as directly on apoB-100,
      Lp(a), and apoA-I immunocaptured within each fraction (i.e., OxPL/apoB and Lp
      PLA(2)/apoB). In whole fractions, OxPL was primarily detected in the Lp(a)
      containing fractions, whereas Lp-PLA(2) was primarily detected in the small,
      dense LDL and light Lp(a) range. In lipoprotein capture assays, OxPL/apoB and
      OxPL/apo(a) increased proportionally with increasing Lp(a) levels. Lp-PLA(2)/apoB
      and Lp-PLA(2)/apoA-I levels were highest in the low Lp(a) group but decreased
      proportionally with increasing Lp(a) levels. Lp-PLA(2)/apo(a) was lowest in
      patients with low Lp(a) levels and increased proportionally with increasing Lp(a)
      levels. Apheresis significantly reduced levels of OxPL and Lp-PLA(2) on apoB and
      Lp(a) (50-75%), particularly in patients with intermediate and high Lp(a) levels.
      In contrast, apheresis increased Lp-PLA(2)-specific activity (activity/mass
      ratio) in buoyant LDL fractions. The impact of apheresis on Lp(a), OxPL, and Lp
      PLA(2) provides insights into its therapeutic benefits beyond lowering apoB
      containing lipoproteins.

PMID- 22628618
TI  - Activating transcription factor 4 regulates stearate-induced vascular
      calcification.
AB  - Previously, we reported that stearate, a saturated fatty acid, promotes
      osteoblastic differentiation and mineralization of vascular smooth muscle cells
      (VSMC). In this study, we examined the molecular mechanisms by which stearate
      promotes vascular calcification. ATF4 is a pivotal transcription factor in
      osteoblastogenesis and endoplasmic reticulum (ER) stress. Increased stearate by
      either supplementation of exogenous stearic acid or inhibition of stearoyl-CoA
      desaturase (SCD) by CAY10566 induced ATF4 mRNA, phosphorylated ATF4 protein, and
      total ATF4 protein. Induction occurred through activation of the PERK-eIF2alpha
      pathway, along with increased osteoblastic differentiation and mineralization of
      VSMCs. Either stearate or the SCD inhibitor but not oleate or other fatty acid
      treatments also increased ER stress as determined by the expression of p
      eIF2alpha, CHOP, and the spliced form of XBP-1, which were directly correlated
      with ER stearate levels. ATF4 knockdown by lentiviral ATF4 shRNA blocked
      osteoblastic differentiation and mineralization induced by stearate and SCD
      inhibition. Conversely, treatment of VSMCs with an adenovirus containing ATF4
      induced vascular calcification. Our results demonstrated that activation of ATF4
      mediates vascular calcification induced by stearate.

PMID- 22628617
TI  - Tsc2, a positional candidate gene underlying a quantitative trait locus for
      hepatic steatosis.
AB  - Nonalchoholic fatty liver disease (NAFLD) is the most common cause of liver
      dysfunction and is associated with metabolic diseases, including obesity, insulin
      resistance, and type 2 diabetes. We mapped a quantitative trait locus (QTL) for
      NAFLD to chromosome 17 in a cross between C57BL/6 (B6) and BTBR mouse strains
      made genetically obese with the Lep(ob/ob) mutation. We identified Tsc2 as a gene
      underlying the chromosome 17 NAFLD QTL. Tsc2 functions as an inhibitor of
      mammalian target of rapamycin, which is involved in many physiological processes,
      including cell growth, proliferation, and metabolism. We found that Tsc2(+/-)
      mice have increased lipogenic gene expression in the liver in an insulin
      dependent manner. The coding single nucleotide polymorphism between the B6 and
      BTBR strains leads to a change in the ability to inhibit the expression of
      lipogenic genes and de novo lipogenesis in AML12 cells and to promote the
      proliferation of Ins1 cells. This difference is due to a different affinity of
      binding to Tsc1, which affects the stability of Tsc2.

PMID- 22628620
TI  - Cultivating global science.

PMID- 22628625
TI  - Archaeology. Dams along Sudanese Nile threaten ancient sites.

PMID- 22628626
TI  - Immigration reform. Senate bills would make room for more STEM graduates.

PMID- 22628619
TI  - Silencing of enzymes involved in ceramide biosynthesis causes distinct global
      alterations of lipid homeostasis and gene expression.
AB  - Dysregulation of ceramide synthesis has been associated with metabolic disorders
      such as atherosclerosis and diabetes. We examined the changes in lipid
      homeostasis and gene expression in Huh7 hepatocytes when the synthesis of
      ceramide is perturbed by knocking down serine pal mitoyltransferase subunits 1,
      2, and 3 (SPTLC123) or dihydroceramide desaturase 1 (DEGS1). Although knocking
      down all SPTLC subunits is necessary to reduce total ceramides significantly,
      depleting DEGS1 is sufficient to produce a similar outcome. Lipidomic analysis of
      distribution and speciation of multiple lipid classes indicates an increase in
      phospholipids in SPTLC123-silenced cells, whereas DEGS1 depletion leads to the
      accumulation of sphingolipid intermediates, free fatty acids, and diacylglycerol.
      When cer amide synthesis is disrupted, the transcriptional profiles indicate
      inhibition in biosynthetic processes, downregulation of genes involved in general
      endomembrane trafficking, and upregulation of endocytosis and endosomal
      recycling. SPTLC123 silencing strongly affects the expression of genes involved
      with lipid metabolism. Changes in amino acid, sugar, and nucleotide metabolism,
      as well as vesicle trafficking between organelles, are more prominent in DEGS1
      silenced cells. These studies are the first to provide a direct and comprehensive
      understanding at the lipidomic and transcriptomic levels of how Huh7 hepatocytes
      respond to changes in the inhibition of ceramide synthesis.

PMID- 22628627
TI  - Science funding. NSF's 'Big Pitch' tests anonymized grant reviews.

PMID- 22628628
TI  - Planetary science. Homegrown organic matter found on Mars, but no life.

PMID- 22628629
TI  - Alternative energy. Military's plan to buy biofuels hits roadblock in U.S. House.

PMID- 22628630
TI  - Psychology. NSF gives clinical students a shot at winning graduate fellowships.

PMID- 22628631
TI  - Evolutionary biology. An evolutionary theory of dentistry.

PMID- 22628632
TI  - Evolutionary biology. The burdens of being a biped.

PMID- 22628633
TI  - The biology of genomes. Single-cell sequencing tackles basic and biomedical
      questions.

PMID- 22628634
TI  - The biology of genomes. HDL itself does not prevent heart attacks.

PMID- 22628635
TI  - Support for Greece.

PMID- 22628636
TI  - "Two heads are better" stands to reason.

PMID- 22628637
TI  - Life in science. The noblest lesson.

PMID- 22628638
TI  - Science policy. From "science in Europe" to "European science".

PMID- 22628639
TI  - Development. Pushing your back into place.

PMID- 22628640
TI  - Biochemistry. Guided tour to the heart of RISC.

PMID- 22628641
TI  - Biochemistry. Resolving some old problems in protein crystallography.

PMID- 22628642
TI  - Psychology. Kinship and human thought.

PMID- 22628643
TI  - Physics. Enter the Majorana fermion.

PMID- 22628644
TI  - Cancer. Systems biology, metabolomics, and cancer metabolism.

PMID- 22628645
TI  - Physiology. An avian magnetometer.

PMID- 22628646
TI  - IBI* series winner. Learning biology by recreating and extending mathematical
      models.

PMID- 22628647
TI  - Predicting pragmatic reasoning in language games.
AB  - One of the most astonishing features of human language is its capacity to convey
      information efficiently in context. Many theories provide informal accounts of
      communicative inference, yet there have been few successes in making precise,
      quantitative predictions about pragmatic reasoning. We examined judgments about
      simple referential communication games, modeling behavior in these games by
      assuming that speakers attempt to be informative and that listeners use Bayesian
      inference to recover speakers' intended referents. Our model provides a close,
      parameter-free fit to human judgments, suggesting that the use of information
      theoretic tools to predict pragmatic reasoning may lead to more effective formal
      models of communication.

PMID- 22628648
TI  - Unidirectional growth of microbumps on (111)-oriented and nanotwinned copper.
AB  - Highly oriented [111] Cu grains with densely packed nanotwins have been
      fabricated by direct-current electroplating with a high stirring rate. The [111]
      oriented and nanotwinned Cu (nt-Cu) allow for the unidirectional growth of
      Cu(6)Sn(5) intermetallics in the microbumps of three-dimensional integrated
      circuit packaging; a uniform microstructure in a large number of microbumps of
      controlled orientation can be obtained. The high-density twin boundaries in the
      nt-Cu serve as vacancy sinks during the solid-state reaction between Pb-free
      solder and Cu and greatly reduce the formation of Kirkendall (or Frenkel) voids.

PMID- 22628649
TI  - Real-time imaging of Pt3Fe nanorod growth in solution.
AB  - The growth of colloidal nanocrystal architectures by nanoparticle attachment is
      frequently reported as an alternative to the conventional growth by monomer
      attachment. However, the mechanism whereby nanoparticle attachment proceeds
      microscopically remains unclear. We report real-time transmission electron
      microscopy (TEM) imaging of the solution growth of Pt(3)Fe nanorods from
      nanoparticle building blocks. Observations revealed growth of winding
      polycrystalline nanoparticle chains by shape-directed nanoparticle attachment
      followed by straightening and orientation and shape corrections to yield single
      crystal nanorods. Tracking nanoparticle growth trajectories allowed us to
      distinguish the force fields exerted by single nanoparticles and nanoparticle
      chains. Such quantification of nanoparticle interaction and understanding the
      growth pathways are important for the design of hierarchical nanomaterials and
      controlling nanocrystal self-assembly for functional devices.

PMID- 22628650
TI  - Direction-specific interactions control crystal growth by oriented attachment.
AB  - The oriented attachment of molecular clusters and nanoparticles in solution is
      now recognized as an important mechanism of crystal growth in many materials, yet
      the alignment process and attachment mechanism have not been established. We
      performed high-resolution transmission electron microscopy using a fluid cell to
      directly observe oriented attachment of iron oxyhydroxide nanoparticles. The
      particles undergo continuous rotation and interaction until they find a perfect
      lattice match. A sudden jump to contact then occurs over less than 1 nanometer,
      followed by lateral atom-by-atom addition initiated at the contact point.
      Interface elimination proceeds at a rate consistent with the curvature dependence
      of the Gibbs free energy. Measured translational and rotational accelerations
      show that strong, highly direction-specific interactions drive crystal growth via
      oriented attachment.

PMID- 22628651
TI  - Large-pore apertures in a series of metal-organic frameworks.
AB  - We report a strategy to expand the pore aperture of metal-organic frameworks
      (MOFs) into a previously unattained size regime (>32 angstroms). Specifically,
      the systematic expansion of a well-known MOF structure, MOF-74, from its original
      link of one phenylene ring (I) to two, three, four, five, six, seven, nine, and
      eleven (II to XI, respectively), afforded an isoreticular series of MOF-74
      structures (termed IRMOF-74-I to XI) with pore apertures ranging from 14 to 98
      angstroms. All members of this series have noninterpenetrating structures and
      exhibit robust architectures, as evidenced by their permanent porosity and high
      thermal stability (up to 300 degrees C). The pore apertures of an oligoethylene
      glycol-functionalized IRMOF-74-VII and IRMOF-74-IX are large enough for natural
      proteins to enter the pores.

PMID- 22628652
TI  - Linking petrology and seismology at an active volcano.
AB  - Many active volcanoes exhibit changes in seismicity, ground deformation, and gas
      emissions, which in some instances arise from magma movement in the crust before
      eruption. An enduring challenge in volcano monitoring is interpreting signs of
      unrest in terms of the causal subterranean magmatic processes. We examined over
      300 zoned orthopyroxene crystals from the 1980-1986 eruption of Mount St. Helens
      that record pulsatory intrusions of new magma and volatiles into an existing
      larger reservoir before the eruption occurred. Diffusion chronometry applied to
      orthopyroxene crystal rims shows that episodes of magma intrusion correlate
      temporally with recorded seismicity, providing evidence that some seismic events
      are related to magma intrusion. These time scales are commensurate with
      monitoring signals at restless volcanoes, thus improving our ability to forecast
      volcanic eruptions by using petrology.

PMID- 22628653
TI  - Temperature-dependent alterations in host use drive rapid range expansion in a
      butterfly.
AB  - Responses of species to climate change are extremely variable, perhaps because of
      climate-related changes to interactions among species. We show that temperature
      related changes in the dependence of the butterfly Aricia agestis on different
      larval host plants have facilitated rapid range expansion. Historically, the
      butterfly was largely restricted to a single plant species, Helianthemum
      nummularium, but recent warmer conditions have enabled the butterfly to
      increasingly use the more widespread plant species Geranium molle. This has
      resulted in a substantial increase in available habitat and rapid range expansion
      by the butterfly (79 kilometers northward in Britain in 20 years). Interactions
      among species are often seen as constraints on species' responses to climate
      change, but we show that temperature-dependent changes to interspecific
      interactions can also facilitate change.

PMID- 22628654
TI  - Linking crystallographic model and data quality.
AB  - In macromolecular x-ray crystallography, refinement R values measure the
      agreement between observed and calculated data. Analogously, R(merge) values
      reporting on the agreement between multiple measurements of a given reflection
      are used to assess data quality. Here, we show that despite their widespread use,
      R(merge) values are poorly suited for determining the high-resolution limit and
      that current standard protocols discard much useful data. We introduce a
      statistic that estimates the correlation of an observed data set with the
      underlying (not measurable) true signal; this quantity, CC*, provides a single
      statistically valid guide for deciding which data are useful. CC* also can be
      used to assess model and data quality on the same scale, and this reveals when
      data quality is limiting model improvement.

PMID- 22628655
TI  - Structures from anomalous diffraction of native biological macromolecules.
AB  - Crystal structure analyses for biological macromolecules without known structural
      relatives entail solving the crystallographic phase problem. Typical de novo
      phase evaluations depend on incorporating heavier atoms than those found
      natively; most commonly, multi- or single-wavelength anomalous diffraction (MAD
      or SAD) experiments exploit selenomethionyl proteins. Here, we realize routine
      structure determination using intrinsic anomalous scattering from native
      macromolecules. We devised robust procedures for enhancing the signal-to-noise
      ratio in the slight anomalous scattering from generic native structures by
      combining data measured from multiple crystals at lower-than-usual x-ray energy.
      Using this multicrystal SAD method (5 to 13 equivalent crystals), we determined
      structures at modest resolution (2.8 to 2.3 angstroms) for native proteins
      varying in size (127 to 1148 unique residues) and number of sulfur sites (3 to
      28). With no requirement for heavy-atom incorporation, such experiments provide
      an attractive alternative to selenomethionyl SAD experiments.

PMID- 22628656
TI  - Metabolite profiling identifies a key role for glycine in rapid cancer cell
      proliferation.
AB  - Metabolic reprogramming has been proposed to be a hallmark of cancer, yet a
      systematic characterization of the metabolic pathways active in transformed cells
      is currently lacking. Using mass spectrometry, we measured the consumption and
      release (CORE) profiles of 219 metabolites from media across the NCI-60 cancer
      cell lines, and integrated these data with a preexisting atlas of gene
      expression. This analysis identified glycine consumption and expression of the
      mitochondrial glycine biosynthetic pathway as strongly correlated with rates of
      proliferation across cancer cells. Antagonizing glycine uptake and its
      mitochondrial biosynthesis preferentially impaired rapidly proliferating cells.
      Moreover, higher expression of this pathway was associated with greater mortality
      in breast cancer patients. Increased reliance on glycine may represent a
      metabolic vulnerability for selectively targeting rapid cancer cell
      proliferation.

PMID- 22628658
TI  - Kinship categories across languages reflect general communicative principles.
AB  - Languages vary in their systems of kinship categories, but the scope of possible
      variation appears to be constrained. Previous accounts of kin classification have
      often emphasized constraints that are specific to the domain of kinship and are
      not derived from general principles. Here, we propose an account that is founded
      on two domain-general principles: Good systems of categories are simple, and they
      enable informative communication. We show computationally that kin classification
      systems in the world's languages achieve a near-optimal trade-off between these
      two competing principles. We also show that our account explains several specific
      constraints on kin classification proposed previously. Because the principles of
      simplicity and informativeness are also relevant to other semantic domains, the
      trade-off between them may provide a domain-general foundation for variation in
      category systems across languages.

PMID- 22628657
TI  - FKF1 conveys timing information for CONSTANS stabilization in photoperiodic
      flowering.
AB  - Plants use day-length information to coordinate flowering time with the
      appropriate season to maximize reproduction. In Arabidopsis, the long day
      specific expression of CONSTANS (CO) protein is crucial for flowering induction.
      Although light signaling regulates CO protein stability, the mechanism by which
      CO is stabilized in the long-day afternoon has remained elusive. Here, we
      demonstrate that FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1) protein stabilizes
      CO protein in the afternoon in long days. FKF1 interacts with CO through its LOV
      domain, and blue light enhances this interaction. In addition, FKF1
      simultaneously removes CYCLING DOF FACTOR 1 (CDF1), which represses CO and
      FLOWERING LOCUS T (FT) transcription. Together with CO transcriptional
      regulation, FKF1 protein controls robust FT mRNA induction through multiple
      feedforward mechanisms that accurately control flowering timing.

PMID- 22628659
TI  - Inter-rater reliability of self-reported response on foreskin status in
      questionnaire among Japanese adult men.
AB  - OBJECTIVES: To determine whether foreskin status is a measurable marker for
      evaluating the effect of the foreskin on sexually transmitted infections.
      METHODS: Inter-rater comparison of the responses on foreskin status and
      circumcision in a self-report questionnaire with the findings of a physical
      examination by an experienced well-trained urologist was performed for patients
      who visited a healthcare facility in Kanagawa, Japan. Foreskin status was defined
      using a five-point graphical scale based on the degree to which the foreskin
      covers the foreskin and the glans penis in a non-erectile condition: type 1, a
      fully exposed glans penis; types 2-4, the glans penis partly covered by the
      foreskin and type 5, phimosis. Linear weighted kappa and per cent agreement were
      used to evaluate the reliability of responses. RESULTS: Among 188 participants
      who were evaluated about their foreskin status, linear weighted kappa and per
      cent agreement were 0.74% and 68.4%, respectively. Linear weighted kappa improved
      from 0.74 to 0.80 when the number of categories was changed to three. All the
      self-reported responses on circumcision were in agreement with the findings of
      the physical examination. Seventeen participants (9.0%) had been circumcised, and
      among them, three (17.6%) had approximately one-half of their glans penis covered
      by the foreskin. In 90 among the 171 uncircumcised participants (52.6%), the
      foreskin did not cover the glans penis. CONCLUSIONS: The self-reported response
      on foreskin status in this questionnaire has sufficient reliability to replace
      physical examination, and this questionnaire can facilitate further studies about
      the effect of foreskin on sexually transmitted infections.

PMID- 22628660
TI  - A cross-sectional survey of attitudes to HIV risk and rapid HIV testing among
      clients of sex workers in Switzerland.
AB  - OBJECTIVES: To assess attitudes to HIV risk and acceptability of rapid HIV
      testing among clients of street-based female sex workers (FSW) in Lausanne,
      Switzerland, where HIV prevalence in the general population is 0.4%. METHODS: The
      authors conducted a cross-sectional study in the red light district of Lausanne
      for five nights in September of 2008, 2009 and 2010. Clients of FSW were invited
      to complete a questionnaire in the street assessing demographic characteristics,
      attitudes to HIV risk and HIV testing history. All clients interviewed were then
      offered anonymous finger stick rapid HIV testing in a van parked on-site.
      RESULTS: The authors interviewed 112, 127 and 79 clients in 2008, 2009 and 2010,
      respectively. All were men, average age 32-37 years old; 40-60% were in a stable
      relationship. History of unprotected sex was higher with non-commercial partners
      (33-50%) than with FSW (6-11%); 29-46% of clients had never undergone an HIV
      test. Anonymous rapid HIV testing was accepted by 45-50% of clients. Out of 109
      HIV tests conducted during the three study periods, none was reactive.
      CONCLUSIONS: On-site HIV counselling and testing is acceptable among clients of
      FSW in this urban setting. These individuals represent an unquantified
      population, a proportion of which has an incomplete understanding of HIV risk in
      the face of high-risk behaviour, with implications for potential onward
      transmission to non-commercial sexual partners.

PMID- 22628661
TI  - High-risk human papillomavirus prevalence is associated with HIV infection among
      heterosexual men in Rakai, Uganda.
AB  - OBJECTIVES: Human papillomavirus (HPV) infection causes genital warts, penile
      cancer and cervical cancer. Africa has one of the highest rates of penile and
      cervical cancers, but there are little data on high-risk human papillomavirus (HR
      HPV) prevalence in heterosexual men. Knowledge of HR-HPV prevalence, risk factors
      and genotype distribution among heterosexual men is important to establish risk
      reduction prevention strategies. METHODS: 1578 uncircumcised men aged 15-49 years
      who enrolled in male circumcision trials in Rakai, Uganda, were evaluated for HR
      HPV from swabs of the coronal sulcus/glans using Roche HPV Linear Array. Adjusted
      prevalence risk ratios (adjPRRs) were estimated using modified Poisson
      multivariable regression. RESULTS: HPV prevalence (either high risk or low risk)
      was 90.7% (382/421) among HIV-positive men and 60.9% (596/978) among HIV-negative
      men (PRR 1.49, 95% CI 1.40 to 1.58). HIV-positive men had a significantly higher
      risk of infection with three or more HR-HPV genotypes (PRR=5.76, 95% CI 4.27 to
      7.79). Among HIV-positive men, high-risk sexual behaviours were not associated
      with increased HR-HPV prevalence. Among HIV-negative men, HR-HPV prevalence was
      associated with self-reported genital warts (adjPRR 1.57, 95% CI 1.07 to 2.31).
      Among all men (both HIV negative and HIV positive), HR-HPV prevalence was
      associated with more than 10 lifetime sexual partners (adjPRR 1.30, 95% CI 1.01
      to 1.66), consistent condom use (adjPRR 1.31, 95% CI 1.08 to 1.60) and HIV
      infection (adjPRR 1.80, 95% CI 1.60 to 2.02). HR-HPV prevalence was lower among
      men who reported no sexual partners during the past year (adjPRR 0.47, 95% CI
      0.23 to 0.94). CONCLUSION: The burden of HR-HPV infection is high among
      heterosexual men in sub-Saharan Africa and most pronounced among the HIV-infected
      individuals.

PMID- 22628662
TI  - Sickle cell disease is associated with decreased HIV but higher HBV and HCV
      comorbidities in U.S. hospital discharge records: a cross-sectional study.
AB  - OBJECTIVE: Some studies suggest that HIV infection progresses slowly in patients
      with sickle cell disease (SCD). The authors aimed to determine the relationships
      between SCD and HIV infection. METHODS: National Hospital Discharge Survey data
      from adult African-Americans in the period of 1997-2009 were analysed. The
      comorbidities of SCD with HIV infections in hospital discharges were analysed.
      Multiple logistic regression was used to test the association between SCD and
      HIV. For comparative purposes, the relationships of SCD with hepatitis B virus
      (HBV) and hepatitis C virus (HCV) were also assessed. RESULTS: 423,431 records
      were divided into two time periods 1997-2003 (53% of records) and 2004-2009 (47%
      of records). The frequency of HIV diagnosis was lower in patients with SCD (1.5%
      vs 3.3% in patients without SCD). In logistic regression, SCD diagnosis was
      associated with an OR of 0.24 (95% CI 0.18 to 0.32) for HIV diagnosis in the
      first period and with an OR of 0.31 (95% CI 0.22 to 0.42) in the second period.
      In contrast, SCD was associated with higher risk of HCV (OR=2.01, 95% CI 1.56 to
      2.59 in the first period and OR=2.12, 95% CI 1.71 to 2.63 in the second period).
      SCD was also associated with a higher risk of HBV (OR=1.15, 95% CI 0.72 to 1.83
      in the first period and OR=1.82, 95% CI 1.24 to 2.68 in the second period).
      CONCLUSIONS: The lower risk of HIV comorbidity, but not HCV and HBV, with SCD is
      consistent with the possibility that SCD has a unique effect in altering the risk
      of HIV infection or progression. Investigation of how the haemolytic and
      immunological changes of SCD influence HIV might lead to new therapeutic or
      preventive approaches.

PMID- 22628663
TI  - Intermediate vaginal flora is associated with HIV prevalence as strongly as
      bacterial vaginosis in a cross-sectional study of participants screened for a
      randomised controlled trial.
AB  - OBJECTIVE: The authors analysed data from female sex workers screened prior to
      participation in a microbicide trial to examine the association between prevalent
      vaginal flora abnormalities and HIV infection, with special emphasis on the role
      of the intermediate vaginal flora (IVF) in this association. METHODS: Data from
      the Kampala, Cotonou, Chennai and Mudhol/Jamkhandi sites were analysed.
      Participants were interviewed and provided blood for HIV and syphilis antibody
      testing, genital samples for the diagnosis of vaginal flora abnormalities (using
      Nugent score) and other reproductive tract infections. Log-binomial regression
      was used to estimate the HIV prevalence ratio (PR) in relation to IVF and
      bacterial vaginosis (BV). RESULTS: Among 1367 women, BV, IVF and HIV prevalences
      were 47.6% (95% CI=45.0% to 50.3%), 19.2% (95% CI=17.1% to 21.2%) and 27.0% (95%
      CI=24.6% to 29.3%), respectively. In multivariate analysis, adjusting for study
      site, age, years of education, occupation, female sterilisation, oral sex, past
      history of sexually transmitted infection, gonorrhoea and candidiasis, IVF was
      significantly associated with HIV infection with a PR similar to that of BV
      (adjusted PR=1.56 (95% CI=1.22 to 1.98) and 1.48 (95% CI=1.20 to 1.84),
      respectively). CONCLUSIONS: Though the cross-sectional design of the study
      precludes directional interpretation of the findings, the data do suggest that
      IVF may be as important as BV in HIV acquisition. The authors recommend
      prospective research to better understand the association between IVF and HIV
      acquisition.

PMID- 22628664
TI  - Prevalence of HIV and sexually transmitted infections and patterns of recent HIV
      testing among men who have sex with men in Zagreb, Croatia.
AB  - OBJECTIVE: To determine the prevalence of HIV and other sexually transmitted
      infections (STIs) among men who have sex with men (MSM) in Zagreb, Croatia, and
      assess correlates of testing for HIV in the past 12 months. METHODS: The authors
      carried out a bio-behavioural survey using respondent-driven sampling (RDS) from
      September 2010 to February 2011. Participants completed a questionnaire and were
      asked to provide blood, urine, oropharyngeal and rectal swabs for the detection
      of infections. Data were analysed using RDS Analysis Tool 6.0.1 and STATA V.8.0.
      RESULTS: A total of 387 MSM were recruited at the University Hospital for
      Infectious Diseases. The age range of recruited men was 18-57 years. HIV
      prevalence was 2.8% (95% CI 1.1% to 5.1%) (3.6%, unadjusted), lower than that
      found in the first RDS survey carried out in 2006 (4.5%, 95% 2.2% to 7.3%) (4.9%,
      unadjusted). The seroprevalence of herpes virus type 2 was 5.9% (6.9, unadjusted)
      and that of syphilis measured by Treponema pallidum haemagglutination assay was
      7.6% (6.7%, unadjusted). The authors found urethral and/or rectal infections with
      Chlamydia trachomatis in 7.2% (8.5%, unadjusted) of men and gonoccocal in 2.7%
      (2.1%, unadjusted). HIV testing in the past 12 months was reported by 32.7%
      (38.9%, unadjusted). In the multivariate analysis, significant correlates of
      recent HIV testing were having more than three partners in the past 12 months and
      the knowledge of HIV status of a regular partner. CONCLUSIONS: The results
      indicate that there might have not been a progression of an HIV and STI epidemic
      in the past 5 years among MSM in Croatia. Prevention should expand by providing
      better uptake of HIV and STI testing services, thus enabling timely treatment.

PMID- 22628665
TI  - Understanding patient choices for attending sexually transmitted infection
      testing services: a qualitative study.
AB  - OBJECTIVES: To establish which aspects of sexually transmitted infection (STI)
      testing services are important to STI testing service users. METHODS: 10 focus
      groups consisting of previous or existing users of STI testing services were
      conducted in community settings in the south east of England. Groups were quota
      sampled based on age, gender and sexual orientation. Data were analysed using
      Framework Analysis. RESULTS: 65 respondents (58% men) participated. Perceived
      expertise of staff was the key reason for attendance at genitourinary medicine
      services rather than general practice. Although some respondents voiced a
      willingness to test for STIs within general practice, the apparent limited range
      of tests available in general practice and the perceived lack of expertise around
      sexual health appeared to discourage attendance at general practice. The decision
      of where to test for STIs was also influenced by past experience of testing,
      existing relationships with general practice, method of receiving test results
      and whether the patient had other medical conditions such as HIV. CONCLUSIONS: No
      one type of STI testing service is suitable for all patients. This is recognised
      by policymakers, and it now requires commissioners and providers to make services
      outside of genitourinary medicine clinics more acceptable and attractive to
      patients, in particular to address the perceived lack of expertise and limited
      range of STIs tests available at alternative testing sites.

PMID- 22628666
TI  - Sexually transmitted diphtheria.
AB  - Diphtheria is caused by diphtheria toxin-producing Corynebacterium species. While
      classical respiratory diphtheria is transmitted by droplets, cutaneous diphtheria
      often results from minor trauma. This report concerns the first case of sexually
      transmitted diphtheria in a patient with non-gonococcal urethritis after
      orogenital contact.

PMID- 22628667
TI  - Male IDUs who have sex with men in England, Wales and Northern Ireland: are they
      at greater risk of bloodborne virus infection and harm than those who only have
      sex with women?
AB  - OBJECTIVES: In the UK, although transmission of HIV among injecting drug user
      (IDUs) has been limited since the 1980s, IDUs and men who have sex with men (MSM)
      have higher HIV and hepatitis C virus (HCV) prevalences than the general
      population. MSM who are also IDUs (MSM-IDUs) may therefore have a higher risk of
      infection than male IDUs who only have sex with women. METHODS: Analysis of data
      from a national survey of IDUs attending services (England, Wales and Northern
      Ireland) between 1998 and 2007, which collected demographic and behavioural data
      and oral fluid samples for HIV and HCV antibody testing. RESULTS: Of the 8671 men
      who reported injecting drugs and having sex during the preceding year, 96% (8354)
      were men who only had sex with women (MSW). MSM-IDUs and MSW-IDUs had similar age
      and number of years of injecting. MSM-IDUs had a higher prevalence of HIV
      (adjusted OR=4.08, 95% CI 1.9 to 8.5) and of HCV (adjusted OR =1.34, 95% CI 1.1
      to 1.8) and were about four times (adjusted OR =3.78, 95% CI 2.9 to 4.9) more
      likely to have unprotected sex with multiple partners. Among those who injected
      in the 4 weeks prior to participation, the MSM-IDUs had a higher level of
      needle/syringe sharing (adjusted OR =1.72, 95% CI 1.3 to 2.2). DISCUSSION: MSM
      IDUs have a fourfold higher risk of HIV; HCV prevalence in MSM-IDUs is a third
      higher than among MSW-IDUs, suggesting elevated risk from injecting and possibly
      sexual transmission. These findings emphasise the need for public health
      interventions specifically targeted at MSM-IDUs.

PMID- 22628896
TI  - iGuide to plastic surgery: iPhone apps, the plastic surgeon, and the health care
      environment.
AB  - The growth in the adoption of smartphones among clinicians has been phenomenal.
      The demand for medical applications, or "apps," downloaded by smartphone users
      has led to the development of practical and educational apps for clinicians,
      medical students, and patients. In addition to being a valuable resource for the
      clinician, mobile technologies are revolutionizing the nature and delivery of
      health care services. This article summarizes the current trends in the
      smartphone market and explores the medical apps that are currently available.

PMID- 22628897
TI  - Manage your online reputation--or someone else will.
AB  - In the Internet age, managing one's online "reputation" is a challenging but
      important task for board-certified plastic surgeons. In this article, the authors
      discuss the options for ensuring that your Internet presence accurately reflects
      the quality of your practice.

PMID- 22628898
TI  - Why do palliative care patients present to the emergency department? Avoidable or
      unavoidable?
AB  - INTRODUCTION: Presentations by patients with advanced illness to the Emergency
      Department (ED) towards the end-of-life can be distressing for both patients and
      caregivers. With an understanding of why patients present, interventions to avoid
      these presentations close to the end-of-life may be possible. AIMS: To identify
      patients under the specialist palliative care service (SPCS) who attended the ED
      over 6 months and to determine if these presentations were potentially avoidable.
      Presentations were deemed avoidable if the problem could have been dealt with in
      another manner, i.e. by the home care team or by the family physician, or in
      another setting, such as by admission to the hospice. RESULTS: Thirty-five ED
      presentations by 30 patients were included. Eighteen (60%) male, mean age 68.7
      (47-89). Twenty-two (63%) ED presentations were outside working hours. The main
      reasons for attending were: dyspnea (9, 26%), nausea/vomiting/constipation (6,
      17%) and uncontrolled pain (5, 14.5%). Thirty-three (94%) of the 35 presentations
      resulted in hospitalization. The average length of time spent in the ED was 9.2
      hours (3-24). Referral to the hospital SPCS was made in 20 (60%) cases. Fifteen
      (50%) patients died within one month of presentation. Eighteen (51.5%) ED
      presentations were deemed potentially avoidable. CONCLUSION: Many ED
      presentations by palliative care patients may be avoidable. Appropriate sharing
      of information to on-call doctors, creating confidence in carers and providing
      extra practical supports is necessary. A comprehensive, coordinated specialist
      palliative care approach across community and acute services may help ensure
      patients are not sent to the ED inappropriately.

PMID- 22628899
TI  - End-of-live vignette. The mirror.

PMID- 22628901
TI  - NEW RECORDS OF PHLEBOTOMINE SAND FLIES (DIPTERA: PSYCHODIDAE) FROM ECUADOR.
AB  - The number of recorded phlebotomine sand fly species in Ecuador has nearly
      doubled during the past 20 years as a result of surveys. In 2005, a sand fly
      survey of two localities, Tiputini in the Amazon rain forest and Paraiso
      Escondido in the Pacific coastal lowland forest, resulted in the capture of 25
      species. New records for Ecuador consisted of five species from the Amazonian
      region and one from Paraiso Escondido. The Amazonian species were Nyssomyia
      richardwardi (Ready and Fraiha), Psathyromyia dreisbachi (Causey and Damasceno),
      Psathyromyia runoides (Fairchild and Hertig), Trichophoromyia pabloi (Barretto,
      Burbano and Young), and Trichopygomyia witoto (Young and Morales). The Pacific
      coastal lowland species was Psathyromyia punctigeniculata (Floch and Abonnenc).

PMID- 22628902
TI  - Sex Ratio, Conflict Dynamics, and Wounding in Rhesus Macaques (Macaca mulatta).
AB  - Rhesus macaques, like many other primates, live in stable, multi-male multi
      female groups in which adult females typically outnumber adult males. The number
      of males in multi-male/multi-female groups is most commonly discussed in terms of
      mate competition, where the sex ratio is a function of an adult male's ability to
      monopolize a group of females. However, the relationship between sex ratio and
      group stability is unclear because the presence of many males may either reduce
      stability by increasing mate competition or may improve stability if adult males
      are key conflict managers. We investigated the relationship between sex ratio,
      male intervention behavior, and trauma in seven groups of captive rhesus
      macaques. Our results show that high-ranking adult males intervene twice as
      frequently as adult females (P<0.0001) and are about twice as successful
      (P<0.0001). Furthermore, the type of adult males present in the group affects the
      relationship between intervention behavior and rate of traumas: males must be
      unrelated to the highest-ranking matrilines. Groups with a lower ratio of females
      per male unrelated to the alpha and beta matrilines had better intervention
      success (P<0.04) and fewer traumas requiring veterinary care (P=0.003). We
      conclude that conflict management behavior by adult males, particularly those
      unrelated to the highest-ranking matrilines, is the mechanism by which sex ratio
      influences the frequency of traumas, and thus group stability. We therefore
      suggest that monitoring and managing the sex ratio of captive primate groups is
      one of many measurements to predict group stability.

PMID- 22628904
TI  - Message from his excellency the minister of health and family welfare, government
      of India.

PMID- 22628903
TI  - Parent-adolescent concordance on perceived need for mental health services and
      its impact on service use.
AB  - Mental health service underutilization among African American adolescents is well
      documented, yet not fully understood. Discordance between adolescents and their
      parents on perceived need for seeing a counselor for an emotional need or
      psychiatrist for psychiatric or medical services may help explain low service use
      among this population. This exploratory, prospective study examined the
      relationship between parent-adolescent concordance on perceived need for
      emotional counseling or psychiatric services and mental health service use. The
      relationships between gender and perceived service need and concordance and
      adolescent severity of depressive symptoms were also explored. Parent-adolescent
      dyads (n=108) receiving community-based adolescent outpatient mental health
      services responded to interview questions concerning their perception of whether
      an emotional counselor and a psychiatrist were needed in the past six months.
      Findings revealed low parent-adolescent concordance on perceived need for an
      emotional counselor and a psychiatrist. A greater proportion of adolescents
      reported a need than parents. There was no association between gender and
      perceived need for an emotional counselor and a psychiatrist. Lower rates of
      parent-adolescent concordance were found among youth reporting elevated
      depressive symptoms compared to youth reporting normal range symptoms. Concordant
      dyads kept a higher number of appointments than discordant dyads. Implications
      for clinical social work practice and future research are discussed.

PMID- 22628905
TI  - Social and Economic Implications of Noncommunicable diseases in India.
AB  - Noncommunicable diseases (NCDs) have become a major public health problem in
      India accounting for 62% of the total burden of foregone DALYs and 53% of total
      deaths. In this paper, we review the social and economic impact of NCDs in India.
      We outline this impact at household, health system and the macroeconomic level.
      Cardiovascular diseases (CVDs) figure at the top among the leading ten causes of
      adult (25-69 years) deaths in India. The effects of NCDs are inequitable with
      evidence of reversal in social gradient of risk factors and greater financial
      implications for the poorer households in India. Out-of-pocket expenditure
      associated with the acute and long-term effects of NCDs is high resulting in
      catastrophic health expenditure for the households. Study in India showed that
      about 25% of families with a member with CVD and 50% with cancer experience
      catastrophic expenditure and 10% and 25%, respectively, are driven to poverty.
      The odds of incurring catastrophic hospitalization expenditure were nearly 160%
      higher with cancer than the odds of incurring catastrophic spending when
      hospitalization was due to a communicable disease. These high numbers also pose
      significant challenge for the health system for providing treatment, care and
      support. The proportion of hospitalizations and outpatient consultations as a
      result of NCDs rose from 32% to 40% and 22% to 35%, respectively, within a decade
      from 1995 to 2004. In macroeconomic term, most of the estimates suggest that the
      NCDs in India account for an economic burden in the range of 5-10% of GDP, which
      is significant and slowing down GDP thus hampering development. While India is
      simultaneously experiencing several disease burdens due to old and new
      infections, nutritional deficiencies, chronic diseases, and injuries, individual
      interventions for clinical care are unlikely to be affordable on a large scale.
      While it is clear that "treating our way out" of the NCDs may not be the
      efficient way, it has to be strongly supplemented with population-based services
      aimed at health promotion and action on social determinants of health along with
      individual services. Since health sector alone cannot deal with the "chronic
      emergency" of NCDs, a multi-sectoral action addressing the social determinants
      and strengthening of health systems for universal coverage to population and
      individual services is required.

PMID- 22628906
TI  - Road map and challenges for universal coverage for prevention and control of
      noncommunicable diseases in India.

PMID- 22628908
TI  - Strengthening the health system to better confront noncommunicable diseases in
      India.
AB  - The paper emphasizes the vital need to address the rising burden of
      noncommunicable diseases (NCDs) in India with a health systems approach. The
      authors argue that adoption of such approach may soon be imperative. Applying the
      health systems framework developed by the WHO in 2000 to NCDs means in summary re
      examining the planning and organization of the entire health system, from service
      provision to financing, from information generation to ensuring adequate supply
      of pharmaceuticals/technologies or human resources, from improving facility
      management to performance monitoring. Using this framework the authors seek to
      highlight core issues and identify possible policy actions required. The
      challenge is to ensure the best implementation of what works, aligning the
      service provision function with the financial incentives, ensuring
      leadership/stewardship by the government across local/municipal, state or
      regional and national level while involving stakeholders. A health system
      perspective would also ensure that action against NCD goes hand in hand with
      tackling the remaining burden from communicable diseases, maternal, child health
      and nutrition issues.

PMID- 22628907
TI  - What are the Evidence Based Public Health Interventions for Prevention and
      Control of NCDs in Relation to India?
AB  - The accelerating epidemics of noncommunicable diseases (NCDs) in India call for a
      comprehensive public health response which can effectively combat and control
      them before they peak and inflict severe damage in terms of unaffordable health,
      economic, and social costs. To synthesize and present recent evidences regarding
      the effectiveness of several types of public health interventions to reduce NCD
      burden. Interventions influencing behavioral risk factors (like unhealthy diet,
      physical inactivity, tobacco and alcohol consumption) through policy, public
      education, or a combination of both have been demonstrated to be effective in
      reducing the NCD risk in populations as well as in individuals. Policy
      interventions are also effective in reducing the levels of several major
      biological risk factors linked to NCDs (high blood pressure; overweight and
      obesity; diabetes and abnormal blood cholesterol). Secondary prevention along the
      lines of combination pills and ensuring evidenced based clinical care are also
      critical. Though the evidence for health promotion and primary prevention are
      weaker, policy interventions and secondary prevention when combined with these
      are likely to have a greater impact on reducing national NCD burden. A
      comprehensive and integrated response to NCDs control and prevention needs a
      "life course approach." Proven cost-effective interventions need to be integrated
      in a NCD prevention and control policy framework and implemented through
      coordinated mechanisms of regulation, environment modification, education, and
      health care responses.

PMID- 22628909
TI  - Promotion of standard treatment guidelines and building referral system for
      management of common noncommunicable diseases in India.
AB  - Treatment services constitute one of the five priority actions to face the global
      crisis due to noncommunicable diseases (NCDs). It is important to formulate
      standard treatment guidelines (STGs) for an effective management, particularly at
      the primary and secondary levels of health care. Dissemination and implementation
      of STGs for NCDs on a country-wide scale involves difficult and complex issues.
      The management of NCDs and the associated costs are highly variable and huge.
      Besides the educational strategies for promotion of STGs, the scientific and
      administrative sanctions and sanctity are important for purposes of
      reimbursements, insurance, availability of facilities, and legal protection. An
      effective and functional referral- system needs to be built to ensure
      availability of appropriate care at all levels of health- services. The patient
      friendly "to and fro" referral system will help to distribute the burden, lower
      the costs, and maintain the sustainability of services.

PMID- 22628910
TI  - Relevance of primary health care in controlling noncommunicable diseases in
      India.

PMID- 22628911
TI  - Multi-sectoral action for addressing social determinants of noncommunicable
      diseases and mainstreaming health promotion in national health programmes in
      India.
AB  - Major noncommunicable diseases (NCDs) share common behavioral risk factors and
      deep-rooted social determinants. India needs to address its growing NCD burden
      through health promoting partnerships, policies, and programs. High-level
      political commitment, inter-sectoral coordination, and community mobilization are
      important in developing a successful, national, multi-sectoral program for the
      prevention and control of NCDs. The World Health Organization's "Action Plan for
      a Global Strategy for Prevention and Control of NCDs" calls for a comprehensive
      plan involving a whole-of-Government approach. Inter-sectoral coordination will
      need to start at the planning stage and continue to the implementation,
      evaluation of interventions, and enactment of public policies. An efficient multi
      sectoral mechanism is also crucial at the stage of monitoring, evaluating
      enforcement of policies, and analyzing impact of multi-sectoral initiatives on
      reducing NCD burden in the country. This paper presents a critical appraisal of
      social determinants influencing NCDs, in the Indian context, and how multi
      sectoral action can effectively address such challenges through mainstreaming
      health promotion into national health and development programs. India, with its
      wide socio-cultural, economic, and geographical diversities, poses several unique
      challenges in addressing NCDs. On the other hand, the jurisdiction States have
      over health, presents multiple opportunities to address health from the local
      perspective, while working on the national framework around multi-sectoral
      aspects of NCDs.

PMID- 22628912
TI  - Noncommunicable diseases risk factor surveillance: experience and challenge from
      India.
AB  - Noncommunicable diseases (NCDs) are reaching epidemic proportions worldwide and
      in India. Surveillance of NCD risk factors are therefore needed as they could
      help in policy planning and implementation of preventive measures. This article
      will focus on the experiences gained, and challenges faced, in conducting NCD
      risk factor surveillance studies in India. Two major surveillance studies on NCDs
      were conducted in India - the World Health Organization (WHO) - Indian Council of
      Medical Research (ICMR) NCD risk factor surveillance study and the Integrated
      Disease Surveillance Project (IDSP). The WHO-ICMR study was a six-site pilot
      study representing six different geographical locations in India with a sample
      size of 44,537 including rural, peri-urban/slum and urban. Phase 1 of the IDSP
      was completed and included seven states in India with a sample size of 5000 per
      state. The NCD risk factor surveillance showed that high prevalence of diabetes,
      hypertension and obesity in urban areas with slightly lower prevalence rates in
      semi-urban and rural areas. There are several challenges in obtaining data on NCD
      risk factors, which include challenges in obtaining anthropometric and blood
      pressure measures and in assessing tobacco consumption, diet and physical
      activity. The challenges in field operations include contacting and convincing
      subjects, creating rapport, tracking subjects, climatic conditions, recall
      ability and interviewer skills. Success in surveillance studies depends on
      anticipating and managing these challenges CONCLUSION: Improving country-level
      surveillance and monitoring is a valuable step in prevention and control of NCDs
      in India.

PMID- 22628913
TI  - How to Effectively Monitor and Evaluate NCD Programmes in India.
AB  - Program monitoring and evaluation (M and E) are important components of any
      program and are critical to sound strategic planning. The Ministry of Health and
      Family Welfare, Government of India, launched the National Programme for
      Prevention and Control of Cancer, Diabetes, Cardio-vascular diseases and Stroke
      (NPCDCS) with the objectives to prevent and control common noncommunicable
      diseases (NCDs) through behaviour and lifestyle changes, and to provide early
      diagnosis and management of common NCDs. M and E of program requires
      identification of indicators that measure inputs, process, outputs, and outcomes.
      The frequency of collecting information for these indicators will vary depending
      on the level of use and type of indicator as well as time interval over which we
      expect to see a change in that parameter. A group of indicators for different
      domains in the three major strategies has been proposed. For effective monitoring
      and evaluation of NPCDCS, the way forward is to finalize the list of indicators;
      evolve sustainable systems for surveillance; collect baseline assessment of the
      indicators at district level; fix targets for each indicator for different time
      frames; periodic review at state and national level for monitoring progress; and
      establish external review mechanisms. Monitoring and evaluation require complex
      set of co-ordinated action, responsibility for which has to be taken up by the
      NCD Cell within the Ministries of Health at state and national level. However,
      the routine data collection and compilation could be the responsibility of
      Central Bureau of Health Intelligence. Integrated population-based surveys with
      existing disease and behaviour surveillance could be undertaken by National
      Centre for Disease Control. The national NCD cell should compile all these
      information into a meaningful policy brief so that appropriate programmatic
      interventions can be identified. The launch of a national program to tackle the
      burden of NCDs is just the beginning, and the final success of the program will
      depend on how effectively we monitor and evaluate it.

PMID- 22628914
TI  - Role of medical education in preventing and control of noncommunicable diseases
      in India?
AB  - India has approximately 335 medical colleges, which produce around 40,000 medical
      graduates annually. Even though medical professional have a critical role in
      prevention and control of noncommunicable diseases (NCDs) including injuries, it
      has been observed that the present medical and nursing curriculum in India does
      not adequately cover prevention and control of NCDs. The topics for specific
      approach to prevent NCDs and various strategies can be incorporated into public
      health and clinical courses in undergraduate medical education, with brief
      optional courses in residency and continuing medical education for established
      practitioners. High-level expert group instituted by Planning Commission of India
      on Universal Health Coverage recommended that medical education requires greater
      orientation of providers to the social determinants of health as well as to
      gender and equity issues. Curricula in medical schools should keep pace with the
      changing dynamics of public health, health policy, and health demographics.
      Medical education and training should be reoriented by introducing competency
      based, health system connected curricula, and continuous education. There is a
      need to review of medical curriculum, introducing innovative integrated teaching
      methods, and capacity building of teachers for meeting the challenge of rising
      burden of NCDs in India.

PMID- 22628915
TI  - Integrating services for noncommunicable diseases prevention and control: use of
      primary health care approach.
AB  - Noncommunicable diseases (NCDs) are now the leading cause of death in the South
      East Asia Region, accounting for 55% of all deaths annually. Besides presenting a
      serious threat to public health, NCDs hamper socioeconomic development in the
      region. The situation is likely to worsen in the future. Fortunately, cost
      effective and high-impact interventions to prevent and control NCDs are, however,
      available and at individual level, they cost next to nothing. In order to ensure
      that these interventions are delivered in an efficient and effective manner and
      have the desired impact especially in light of the prevailing economic
      difficulties, an integrated approach is necessary. Different approaches to
      integration can be used although integrating NCD interventions into the health
      system based on primary health care remain the best model.

PMID- 22628916
TI  - Burden of NCDs, Policies and Programme for Prevention and Control of NCDs in
      India.
AB  - Noncommunicable diseases and injuries account for 52% of deaths in India. Burden
      of noncommunicable diseases and resultant mortality is expected to increase
      unless massive efforts are made to prevent and control NCDs and their risk
      factors. Based on available evidence, cancer, diabetes, hypertension,
      cardiovascular diseases, stroke, chronic obstructive pulmonary disease, chronic
      kidney disease, mental disorders and trauma are the leading causes of morbidity,
      disability and mortality in India. Government of India had supported the States
      in prevention and control of NCDs through several vertical programs since 1980s.
      However, during the 11(th) plan, there was considerable upsurge to prevent and
      control NCDs. New programs were started on a low scale in limited number of
      districts. However, there has not been any considerable change in the burden of
      NCDs. Based on experiences in the past, there is need to emphasize on health
      promotion and preventive measures to reduce exposure to risk factors. Facilities
      and capacity for screening, early diagnosis and effective management are required
      within the public health care system. Public awareness program, integrated
      management and strong monitoring system would be required for successful
      implementation of the program and making services universally accessible in the
      country.

PMID- 22628917
TI  - Research priorities for prevention and control of noncommunicable diseases in
      India.
AB  - India is undergoing a demographic and epidemiological transition which is
      influencing its health. Noncommunicable diseases (NCDs) are posing major health
      and development threats, while we are grappling with communicable diseases and
      maternal and child health-related issues. The major NCDs include cardiovascular
      diseases (including stroke), diabetes, cancer, chronic obstructive pulmonary
      diseases, mental health, and injuries. Tobacco, alcohol, diet, physical
      inactivity, high blood pressure, and obesity are the major risk factors common to
      many chronic diseases. Research on NCDs under the ICMR and through other
      institutions has resulted in the initiation of some national health programs such
      as National Cancer Control Program and District Mental Health Program. Important
      epidemiological descriptions have informed us on the causes and distribution of
      NCDs and their risk factors, including the non-health determinants (poverty,
      education, employment, etc) and health systems assessments, have shown the
      inadequacies in tackling NCDs. Several global efforts and publications have
      provided guidance in shaping the research agenda. The special UN NCD Summit held
      on 19-20 September 2011 brought the world leaders to deliberate on ways to
      address NCDs in a concerted manner through partnerships. In this paper the
      authors review the present status of NCDs and their risk factors in the country
      and propose a strategic research agenda to provide adequate thrust to accelerate
      research towards a useful outcome.

PMID- 22628919
TI  - National Summit on Noncommunicable Diseases Universal Coverage and
      Noncommunicable Diseases: New Delhi Call for Action: New Delhi, India. 23-24
      August 2011 Jointly Organized by Ministry of Health and Family Welfare,
      Government of India and WHO Country Office for India.

PMID- 22628918
TI  - Trend of tobacco use and exposure to secondhand smoke among students aged 13-15
      years in India and selected countries of the South-East Asia region.

PMID- 22628920
TI  - Key recommendations of high-level expert group report on universal health
      coverage for India.

PMID- 22628921
TI  - Metabolic abnormalities in obstructive sleep apnea: A double whammy.

PMID- 22628922
TI  - Directly observed treatment short course in immunocompetent patients of
      tuberculous cervical lymphadenopathy treated in revised national tuberculosis
      control programme.
AB  - BACKGROUND: Prospective observation analysis to evaluate the cure in tuberculous
      cervical lymphadenopathy with directly observed treatment short course category
      III (DOTS CAT III) treatment as per revised national tuberculosis control program
      (RNTCP) at a tertiary care hospital in AP, India, from October 2007 to September
      2009. These cases were followed up for period of 22 months. MATERIALS AND
      METHODS: Total 1521 tuberculous cases were screened in KIMS both pulmonary and
      extra pulmonary cases out of which 146 cases were tuberculous lymphadenitis.
      Fifty cases of tuberculous cervical lymphadenopathy were included after
      diagnostic and treatment algorithm and fine needle biopsy or excision biopsy.
      Patients below 5 yrs, immunocompromised, having diabetes mellitus, pulmonary
      tuberculosis and with other co-morbid conditions were excluded from the study.
      All patients were put on DOTS CAT III as per RNTCP guidelines. Follow-up was done
      every 2 months till 6 months for 1) Constitution symptoms 2) Weight gain or loss
      3) Appetite gain or loss 4) Regression of lymph nodes or increase 5) Compliance
      6) Side effects 7) Failures by demonstration of organism by direct smear, culture
      or histopathological examination. RESULTS: In this study, lymph node regression
      was found in 78% at the end of 2 months, 94% at the end of 4 months and 96% at
      the end of 6 months, 9 patients had regression in size though the nodes were
      palpable, 2 had no regression but fresh lymph nodes appeared on the same side and
      sinus discharge was present, culture was negative in these cases. Two cases had
      immune reconstitution syndrome, constitutional symptoms disappeared and showed
      clinical improvement. Four cases were subjected for surgical intervention.
      CONCLUSION: DOTS CAT III is effective in the treatment of tuberculous cervical
      lymphadenopathy. Compliance was good with minimal, minor side effects, only two
      had immune reconstitution syndrome and two had sinus formation; they were
      referred for surgical intervention, and follow-up of 22 months did not show any
      relapses.

PMID- 22628923
TI  - Atopy is a risk factor for adult asthma in urban community of Southwestern
      Nigeria.
AB  - RATIONALE: Factors affecting asthma course are not clearly elucidated in urban
      communities in developing countries. Furthermore, the interaction between factors
      such as atopy, environmental exposure, urbanization, and helminthic infections in
      modulating asthma have not been well investigated. OBJECTIVES: To determine
      factors, which affect asthma in adults being evaluated at urban tertiary health
      center of Southwestern part of Nigeria. MATERIALS AND METHODS: A random sample of
      24 (12 males, 12 females) consecutive asthmatics seen in the Outpatient Pulmonary
      Clinic of University College Hospital of Ibadan and 27 (13 males, 14 females) age
      and gender-matched controls underwent evaluation, which included blood tests for
      eosinophils, serum IgE, allergy skin tests to eight common environmental
      allergens, and spirometry. The modified version of the questionnaire of the
      International study of Asthma and Allergies in Children (ISAAC) Phase III used by
      the same study group of researchers in Nigeria was used to assess the asthma
      symptoms. Wilcoxon sign-rank tests were used to compare eosinophil counts,
      percentage eosinophils, and allergic skin test between the two groups, while
      paired t test was used to compare spirometry variables. RESULTS: Asthmatics had
      significantly more positive skin reaction to house dust mite and mould than
      controls (P<0.05). Total serum IgE was also significantly higher in asthmatics
      than in controls (mean 210 vs 60 IU/mL; P=0.003). However, no significant
      differences were observed in total eosinophil counts. No significant difference
      in the degree of intestinal helminthes infection in the two groups, which means
      stool parasitism was similar. FEV(1) % was significantly lower in asthmatics
      (P=0.02) but FEV(1) was similar between the two groups (P=0.02). CONCLUSION: The
      elevated levels of IgE and positive skin reactions to some of the common
      environmental allergens suggests an important role of atopy in the expression of
      asthma in this developing country's urban setting. Intestinal parasites were seen
      in both, control and asthma subjects, but appear not to play any role in the
      course of asthma, so also is the blood group, genotype and G6PD status.

PMID- 22628924
TI  - Gender differences in notification rates, clinical forms and treatment outcome of
      tuberculosis patients under the RNTCP.
AB  - INTRODUCTION: An increased notification rate of tuberculosis (TB) in men is seen
      in the SAARC region. In India, the Revised National Tuberculosis Control
      Programme (RNTCP) detects nearly three times more male than female TB patients.
      Gender differences have also been reported in the clinical forms of tuberculous
      disease and in treatment adherence and cure rates in patients undergoing
      treatment for tuberculosis. The present study was undertaken to find out the sex
      differences in the notification rates and treatment outcomes of TB patients
      registered under the RNTCP in a rural tuberculosis unit (TU) in West Bengal.
      MATERIALS AND METHODS: A retrospective record-based study was carried out among a
      total of 3605 cases registered under the RNTCP between January 1999 and June
      2005. Notification rates of TB, clinical forms of TB and disease treatment
      outcomes recorded in the registers were analyzed based on genders. Outcomes were
      defined in accordance with the standard RNTCP definitions. The Z-test for
      proportion (for comparing differences in proportions), Student t-test (for
      comparing mean), and chi(2) test (to see association) were performed for
      statistical analysis. RESULTS: Among the total of 3605 patients, 2498 (69.3%)
      were male and 1107 (30.7%) were female with a male female ratio of 2.25:1. In
      patients less than 20 years of age, the notification rates among males and
      females were similar. In the other age groups, males were more likely to be
      notified compared to females and the difference was statistically significant.
      While new smear positive and retreatment cases were significantly more than in
      males, among females, new smear negative and new extrapulmonary cases were
      significantly higher. Among the new smear positive patients 89.4% of females were
      cured compared to 85.8% of males which was again significant statistically
      (Z=1.70, P<0.05). Male patients outnumbered females in all the unfavorable
      outcomes like death, failure, and default although none of the differences were
      statistically significant (P>0.05). CONCLUSION: The present study demonstrates a
      gender difference in the notification rates, clinical presentations and treatment
      outcomes of patients with tuberculosis. Integrated research is necessary to find
      the reasons for these differences. Such studies will be helpful in improving the
      efficacy of the RNTCP.

PMID- 22628925
TI  - Hydrogen peroxide in exhaled breath condensate: A clinical study.
AB  - OBJECTIVES: To study the ongoing inflammatory process of lung in healthy
      individuals with risk factors and comparing with that of a known diseased
      condition. To study the inflammatory response to treatment. BACKGROUND: Morbidity
      and mortality of respiratory diseases are raising in trend due to increased
      smokers, urbanization and air pollution, the diagnosis of these conditions during
      early stage and management can improve patient's lifestyle and morbidity.
      MATERIALS AND METHODS: One hundred subjects were studied from July 2010 to
      September 2010; the level of hydrogen peroxide concentration in exhaled breath
      condensate was measured using Ecocheck. RESULTS: Of the 100 subjects studied, 23
      were healthy individuals with risk factors (smoking, exposure to air pollution,
      and urbanization); the values of hydrogen peroxide in smokers were 200-2220
      nmol/l and in non-smokers 340-760 nmol/l. In people residing in rural areas
      values were 20-140 nmol/l in non-smokers and 180 nmol/l in smokers. In chronic
      obstructive pulmonary disease cases, during acute exacerbations values were 540
      3040 nmol/l and 240-480 nmol/l following treatment. In acute exacerbations of
      bronchial asthma, values were 400-1140 nmol/l and 100-320 nmol/l following
      treatment. In cases of bronchiectasis, values were 300-340 nmol/l and 200-280
      nmol/l following treatment. In diagnosed pneumonia cases values were 1060-11800
      nmol/l and 540-700 nmol/l following treatment. In interstitial lung diseases,
      values ranged from 220-720 nmol/l and 210-510 nmol/l following treatment.
      CONCLUSION: Exhaled breath condensate provides a non-invasive means of sampling
      the lower respiratory tract. Collection of exhaled breath condensate might be
      useful to detect the oxidative destruction of the lung as well as early
      inflammation of the airways in a healthy individual with risk factors and
      comparing the inflammatory response to treatment.

PMID- 22628926
TI  - The role of pleuroscopy in undiagnosed exudative pleural effusion.
AB  - AIMS: To find the diagnostic yield of a pleuroscopic pleural biopsy and to find
      the complication rates. SETTINGS AND DESIGN: Institutional based prospective
      study. MATERIALS AND METHODS: Sixty-eight consecutive patients who had
      undiagnosed exudative pleural effusion were recruited for pleuroscopy from
      September 2007 to August 2010. RESULTS: A total of 68 patients (55 males and 13
      females; mean age 49 years) underwent pleuroscopy. Malignancy was diagnosed in 24
      patients, 22 patients had non-specific inflammation, tuberculosis was found in 16
      patients, empyema was found in 2 patients, 1 patient had sarcoidosis, 1 patient
      had normal pleura and it was non-diagnostic in 2 patients. The diagnostic yield
      was 97%. There were no major complications, only four patients had minor
      complication like subcutaneous emphysema (three patients) and prolonged air leak
      (one patient). CONCLUSIONS: Pleuroscopy is a safe, simple, and valuable tool in
      the diagnosis of undiagnosed exudative pleural effusion with minimal complication
      rates.

PMID- 22628927
TI  - Comparison of helical and axial mode indirect computed tomographic venography in
      patients with pulmonary thromboembolism.
AB  - OBJECTIVE: To compare the helical and axial modes of indirect computed
      tomographic (CT) venography (CTV) for accuracy for diagnosing deep venous
      thrombosis (DVT) of the lower extremities as well as for their radiation burden
      in patients proven to have pulmonary thromboembolism (PTE) on CT pulmonary
      angiography (CTPA). SUBJECTS AND METHODS: Of patients evaluated with CTPA for
      suspected acute PE, 20 of patients who were found to have PTE underwent both
      indirect CTV of the lower extremities and color Doppler examination. For indirect
      CTV, patients were randomly assigned to helical and axial modes. The CTV and
      Doppler findings were interpreted by two experienced radiologists who were
      blinded to the results of each other. RESULTS: Out of total of 260 venous
      segments analyzed (130 venous segments each by helical or axial CTV), thrombi
      were seen in 43 venous segments (15 and 28 each by helical or axial CTV
      respectively). On comparison with Doppler, helical CTV had 82.35% sensitivity and
      99.11% specificity, whereas axial CTV had 96.6% sensitivity and 100% specificity.
      The mean radiation dose was significantly higher for helical (1153.57 mgy.cm) as
      compared to axial mode CTV (806.28 mgy.cm) with P value of <0.0001. CONCLUSION:
      Axial CTV results in decreased radiation dose without significant change in the
      accuracy, as compared to helical CTV in the evaluation of DVT.

PMID- 22628928
TI  - Clinico-epidemiological profile of tobacco users attending a tobacco cessation
      clinic in a teaching hospital in Bangalore city.
AB  - BACKGROUND: Tobacco-attributable mortality in India is estimated to be at least
      10%. Tobacco cessation is more likely to avert millions of deaths before 2050
      than prevention of tobacco use initiation. OBJECTIVE: To describe the clinico
      epidemiological profile of attendees of a tobacco cessation clinic in a teaching
      hospital in Bangalore city. MATERIALS AND METHODS: A descriptive study of 189
      attendees seen over 2 years in the Tobacco Cessation Clinic of a tertiary-care
      teaching hospital in Bangalore, with information on socio demographic
      characteristics, tobacco-use details, nicotine dependence, family/medical
      history, past quit attempts, baseline stage-of-change, and treatment initiated.
      RESULTS: Only 5% were 'walk-in' patients; 98% of attendees were smokers; 97% were
      males. The mean (+/-SD) age of attendees was 48.0 (+/-14.0) years. Most
      participants were married (88%), and predominantly urban (69%). About 62% had
      completed at least 8 years of schooling. Two-thirds of smokers reported high
      levels of nicotine dependence (Fagerstrom score >5/10). About 43% of patients had
      attempted quitting earlier. Four-fifths (79%) of tobacco-users reported a family
      member using tobacco. Commonly documented comorbidities included: Chronic
      respiratory disease (44%), hypertension (23%), diabetes (12%), tuberculosis (9%),
      myocardial infarction (2%), stroke (1%), sexual dysfunction (1%) and cancer
      (0.5%). About 52% reported concomitant alcohol use. At baseline, patients'
      motivational stage was: Precontemplation (14%), contemplation (48%),
      preparation/action (37%) and maintenance (1%). Treatment modalities started were:
      Counseling alone (41%), nicotine replacement therapy alone (NRT) (34%),
      medication alone (13%), and NRT+medication (12%). CONCLUSIONS: This is the first
      study of the baseline profile of patients attending a tobacco cessation clinic
      located within a chest medicine department in India. Important determinants of
      outcome have been captured for follow-up and prospective documentation of
      outcomes.

PMID- 22628929
TI  - Evaluation of correlation between airway and serum inflammatory markers in
      asthmatic patients.
AB  - CONTEXT: Asthma is one of the most common chronic diseases all over the world,
      resulting from a state of persistent sub-acute inflammation of the airways.
      Beside local inflammation, systemic inflammation is also present, which can be
      shown by increased levels of C-reactive protein (CRP). One of the most important
      cells in this disease is eosinophil, and sputum eosinophilia is used for its
      diagnosis. AIMS: The purpose of the present study was to compare and evaluate the
      correlation between CRP level and sputum eosinophilia in asthmatic and control
      subjects. MATERIALS AND METHODS: A total of 61 patients suffering from mild-to
      moderate asthma participated in this study. They were divided into two groups
      based on whether they used inhaled steroid or not. Sputum was induced by
      ultrasonic nebulizer, and then samples of peripheral venous blood were collected
      to measure peripheral cell count and CRP by Enzyme-linked immunosorbent assay
      (ELISA). Thirty-seven healthy subjects were selected and their blood samples were
      taken. Thirty-seven healthy subjects were selected and their blood samples were
      taken. RESULTS: Thirty asthmatic patients in user group (14 females/16 males)
      with the mean age of 39.4+/-9.37 years, 31 asthmatic patients in non-user group
      (13 females/18 males) with the mean age of 35.5+/-8.87 years, and 37 healthy
      controls (17 females/20 males) were included in our study. The mean serum
      concentration of CRP was 2.6 MUg/mL, 3.32 MUg/mL, and 1.16 MUg/mL in user, non
      user, and control groups, respectively. Compared to healthy controls, serum
      concentrations of high sensitivity-CRP (hs-CRP) significantly increased in the
      non-user group (P=0.0001), and user group as well. (P=0.016). The number of
      sputum eosinophils and peripheral blood eosinophils significantly increased in
      the non-users compared to the healthy controls (P=0.0001, P=0.003, respectively).
      In the non-user group, serum hs-CRP levels correlated negatively with FEV(1) and
      positively with numbers of sputum eosinophils, which was not statistically
      significant. Atopy status, age, and sex did not affect hs-CRP levels in both
      asthmatic groups. CONCLUSIONS: It was found that serum concentrations of hs-CRP
      significantly increased in asthmatic patients, and in the steroid-native group it
      partly correlated with FEV(1) and numbers of sputum eosinophils. It suggests that
      serum hs-CRP can indirectly indicate the degree of airway inflammation.

PMID- 22628930
TI  - DOTS for TB relapse in India: A systematic review.
AB  - In India, under the Revised National Tuberculosis Control Program (RNTCP), the
      percentage of smear-positive re-treatment cases is high. The causes of re
      treatment include relapse of the disease after successful completion of
      treatment, treatment failure, and default in treatment. RNTCP does not follow up
      the patients for any period of time after successful completion of treatment to
      determine whether they relapse. Given the high cost of treatment for each patient
      under RNTCP and the potential for spread of disease from these patients, it is
      crucial for the success of the program and control of the disease in the country
      to find out more about the reasons behind this. T0 o conduct a systematic review
      of literature and determine evidence regarding recurrence of TB after its
      successful treatment with standard short course chemotherapy under DOTS
      guidelines. T0 en databases were searched including Medline, Cochrane database,
      Embase and others and reference lists of articles. 255 papers resulted from these
      searches. Seven studies were finally included in the review after applying the
      inclusion, exclusion and quality assessment criteria. R0 elapse rate is high
      (almost 10%) in India which is higher than international studies. Majority of
      relapse cases present soon after completion of treatment (first six months). Risk
      factors for relapse included drug irregularity, initial drug resistance, smoking
      and alcoholism Sex and weight were not risk factors in India. The outcome of
      relapse cases put on treatment is positive but less effective than new cases.
      There are sound arguments and sketchy evidence that DOTS Category 2 treatment may
      not be adequate for retreatment patients.

PMID- 22628931
TI  - Multidrug and extensively drug-resistant tuberculosis management: Evidences and
      controversies.
AB  - Multi-drug and extensively drug resistant tuberculosis (M/XDR-TB) has been an
      area of growing concern among clinicians, epidemiologists, and public health
      workers worldwide. Lack of controlled trials in M/XDR-TB patients hinders the
      optimal management of such patients, and guidelines that have been developed
      based largely on expert opinion are controversial. Lack of new effective drugs,
      improper regimens prescribed by poorly trained doctors and unreliable drug
      susceptibility testing add to the magnitude of the problem. M/XDR-TB is mostly a
      man made problem and its emergence can be checked by prompt diagnosis and
      effective use of first-line drugs in every new patient. DOTS-Plus proposed by
      World Health Organization (WHO) has highlighted the comprehensive management
      strategy to control multi-drug resistant tuberculosis (MDR-TB). Laboratory
      services must be strengthened for adequate and timely diagnosis of M/extensively
      drug resistant tuberculosis (XDR-TB) and programmatic management of M/XDR-TB must
      be scaled up as per target set by global plan to stop TB 2011-2015. In MDR-TB
      patients with localized disease, surgery, as an adjunct to chemotherapy, can
      improve outcomes and should be considered when there is poor response to
      appropriate chemotherapy. Proper use of second-line drugs must be ensured to cure
      existing MDR-TB, to reduce its transmission and to prevent emergence of XDR-TB.

PMID- 22628932
TI  - Intra-thoracic desmoid tumor.
AB  - Desmoid tumor is a rare, benign soft tissue tumor having potential for local
      invasion. It commonly arises in abdominal wall, presenting as a palpable mass. We
      describe a case of thoracic desmoid tumor in a middle aged male arising from the
      chest wall. Unlike the usual presentation, two separate non-palpable tumor masses
      protruded into left thoracic cavity mimicking lung carcinoma. The patient
      underwent successful complete surgical excision of the tumor. Such tumors, being
      rare, may pose diagnostic problems if not considered in the initial work up.

PMID- 22628933
TI  - Pulmonary hypoplasia with hepatic and renal anomalies in a dead fetus.
AB  - Pulmonary hypoplasia is a developmental malformation characterized by incomplete
      development of lung tissue. During routine fetal autopsy of an apparently normal
      female dead fetus of 36 weeks gestation presented completely hypoplastic left
      lung, partially hypoplastic right lung, right-sided shift of heart, right-sided
      shift of trachea, left-sided diaphragmatic hernia through which an extra lobe
      from left lobe of liver extended into the left half of thoracic cavity. Left
      kidney was iliac in position.

PMID- 22628934
TI  - A rare case of acid-fast bacilli in chylothorax.
AB  - Chylothorax is a rare cause of pleural effusion. Here we present a case of
      chylous pleural effusion in which acid-fast bacilli (AFB) was demonstrated (by
      AFB direct smear examination). The patient had been suffering from chronic
      pancreatitis for one year and had undergone pancreatoduodenostomy nine months
      back. He presented with abdominal pain and dyspnea of six months duration and his
      chest skiagram showed right-sided pleural effusion. Thoracocentasis showed milky
      white pleural fluid with triglyceride content of 678 mg/dl, diagnostic of
      chylothorax. The patient clinically improved and his pleural effusion also
      completely resolved with anti-tuberculosis treatment.

PMID- 22628935
TI  - Acute lung injury following transcatheter hepatic arterial chemoembolization of
      doxorubicin-loaded LC beads in a patient with hepatocellular carcinoma.
AB  - Transcatheter arterial chemoembolization (TACE) currently is being used as an
      effective palliative therapy for unresectable cancers especially hepatocelluar
      carcinoma (HCC). Accidental lipiodol embolism to the lungs is a rare but
      potentially fatal complication of TACE. This procedure involves injection of drug
      eluting microspheres (LC Bead) loaded with doxorubicin, followed by embolization
      with embozene microspheres until stasis is evident, being used in advanced HCC.
      We report a patient with inoperable HCC with underlying Hepatitis C and liver
      cirrhosis, who developed acute lung injury following targeted chemoembolization
      of selective feeding hepatic artery with LC beads loaded with doxorubicin. Acute
      lung injury as a complication of unintended lung chemoembolization with
      doxorubicin has not been previously reported in the literature. Interventional
      radiologists screen patients for potential hepatic A-V shunt and take appropriate
      precautions to prevent unintended pulmonary embolization. These include
      appropriate selection of LC bead particle size especially in patients who are
      embolized with radiation pellets. This report highlights the need for a screening
      total body scintigraphy after injection of radionuclide Tc-99 MAA in the feeding
      hepatic artery to identify patients with hepatic A-V shunt. In such patients,
      appropriate size selection of LC bead particles is critical to prevent unintended
      pulmonary chemoembolization and acute lung injury. Other measures include careful
      patient selection, low dose of chemotherapy, and transient selective hepatic vein
      balloon occlusion.

PMID- 22628936
TI  - Bronchial rhinosporidiosis: An unusual presentation.
AB  - Rhinosporidiosis is a granulomatous disease that usually affects the nasal mucosa
      and nasopharynx. The disease is widely prevalent in the tropics, especially in
      southern India and Sri Lanka. In central India, rhinosporidiosis is endemic in
      Raipur, Chhattisgarh. Involvement of the tracheobronchial tree is extremely rare.
      Only two cases of bronchial rhinosporidiosis had been reported in world
      literature. We report a third case of bronchial rhinosporidiosis which occurred
      in a patient with coexisting nasal and nasopharyngeal rhinosporidiosis.
      Bronchoscopic guidance excision of mass and electric cauterization of base was
      done under local anesthesia.

PMID- 22628938
TI  - Giant solitary fibrous tumor pleura: Clinical dilemma and diagnosis.
AB  - Solitary fibrous tumors in the lung are rare neoplasms with distinct
      clinicopathological and immunohistochemical features. We report a giant solitary
      fibrous tumor of the pleura in a young male which remained silent clinically till
      it assumed gigantic proportions. Histology and immunohistochemistry were
      classical of a solitary fibrous tumor. Inspite of its appalling size it proved to
      be benign in behavior. This case depicts the vulnerability of this lesion to a
      clinical bungle. The report highlights the significance of clinical suspicion of
      this rare neoplasm and reveals the diagnostic associations and procedures to
      avoid emperical therapy and delay in curative surgical treatment.

PMID- 22628937
TI  - A 46-year-old man with tracheomegaly, tracheal diverticulosis, and
      bronchiectasis: Mounier-Kuhn syndrome.
AB  - Lower respiratory tract infection is one of the common causes of morbidity in
      India which is occasionally undiagnosed. In this regard tracheobronchomegaly is
      one of those conditions which masquerade as chronic bronchitis and bronchiectasis
      and are usually undiagnosed. It is a well-defined clinical and radiologic entity
      characterized by marked dilatation of the trachea and the central bronchi and is
      frequently associated with recurrent lower respiratory tract infection.
      Tracheobronchomegaly has been described by a variety of names, including Mounier
      Kuhn syndrome, tracheal diverticulosis, tracheobronchiectasis, tracheocele,
      tracheomalacia, and tracheobronchopathia malacia.

PMID- 22628939
TI  - An unusual cause of bronchial obstruction.
AB  - We present here a case of bronchial obstruction secondary to late paradoxical
      reactive enlargement and erosion by mediastinal lymph nodes into the left main
      bronchus in a 26-year-old woman with tuberculosis lymphadenitis. Bronchial
      obstruction due to paradoxical reactions, especially in the late phase of
      treatment, has not been described in adults before.

PMID- 22628940
TI  - Dapsone-induced neutropenia with invasive pulmonary aspergillosis.

PMID- 22628941
TI  - Unexplained hemoptysis.

PMID- 22628942
TI  - TB appearance in chest radiography in Cambodian migrant workers in Bangkok.

PMID- 22628943
TI  - Isoniazid related gynecomastia: Description of a case and systematic review of
      literature.

PMID- 22628944
TI  - Clinical practice of chest physicians for treatment of drug-resistant
      tuberculosis.

PMID- 22628945
TI  - Indexed journal: What does it mean?

PMID- 22628946
TI  - Regarding evaluation of serum immunoglobulin E levels in bronchial asthma.

PMID- 22628947
TI  - Comments on "Chronic obstructive pulmonary disease: Does gender really matter?".

PMID- 22628948
TI  - Author's Reply.

PMID- 22628949
TI  - HAART and ATT in the HIV-positive patient with tuberculosis.

PMID- 22628950
TI  - Boerhaave's syndrome: Spontaneous full thickness esophageal perforation.

PMID- 22628951
TI  - Authorship issues.

PMID- 22628952
TI  - Sputum cytology for lung cancer: Not just part of the past.

PMID- 22628953
TI  - Wisdom beyond bits and bytes........: "The Journal is no longer static - The
      Article has become dynamic!".

PMID- 22628954
TI  - Write to be understood speak to be heard read to grow: -Lawrence Clark Powell.

PMID- 22628955
TI  - Novel and often bizarre strategies in the treatment of periodontal disease.
AB  - Treatment of periodontal disease involves complex mechanical, surgical, and
      medical modalities. Some of the treatment regimens are patient centered, some
      involve a great amount of technical expertise and competence from a practitioner,
      and often involve complex procedures like use of tissue-engineered products. In
      spite of several advances, treatment of periodontal disease depends on scaling
      and root planing and various surgical procedures as the mainstay, but results of
      treatment are not always predictable and are often frustrating. The ultimate aim
      of periodontal treatment is regeneration of periodontal tissues and more
      particularly lost alveolar bone support. The treatment options include a myriad
      of approaches and scientists and researchers have tried various tools and agents
      to improve alveolar bone status and improve periodontal health. These approaches
      vary from simple monotherapy with systemic antibiotic usage to exotic and novel
      procedures like shock wave therapy, photodynamic therapy and application.

PMID- 22628956
TI  - Orthodontic-periodontics interdisciplinary approach.
AB  - In this present era, when a significant number of patients seeking orthodontic
      treatment are adults, importance of multidisciplinary treatment approach cannot
      be overemphasized. Higher susceptibility of plaque accumulation in patients
      undergoing orthodontic treatment makes involvement of periodontist almost
      unavoidable. Also, orthodontic treatment frequently results in undesirable
      periodontal changes which require immediate attention. More recently,
      orthodontics has been used as an adjunct to periodontics to increase connective
      tissue support and alveolar bone height. The purpose of this article is to review
      the adverse effects of orthodontic treatment on the periodontal tissues and to
      discuss the mutually beneficial relationship shared between the two specialties.

PMID- 22628957
TI  - Reduction in HbA1c levels following non-surgical periodontal therapy in type-2
      diabetic patients with chronic generalized periodontitis: A periodontist's role.
AB  - BACKGROUND: Aim of the study was to compare the response to non-surgical
      periodontal therapy between patients with and without type-2 diabetes from
      clinical and metabolic stand point. MATERIALS AND METHODS: A comparative clinical
      study was performed between type 2 diabetics and non-diabetics with moderate
      generalized chronic periodontitis. The study period was six months. Conventional
      periodontal scaling and root planing were performed, and the response to this
      treatment was compared between the groups at three and six months, measuring the
      plaque index, bleeding index, gingival index, and probing depth. In diabetic
      patients, the clinical response was related to measurements of HbA1c and glucose
      in blood at three and six months. STATISTICAL ANALYSIS: Multi Variant Analysis of
      Variance was used to compare following variables between groups and function of
      time. RESULTS: Improvement in all clinical variables was observed in both the
      groups. The improvement observed in blood HbA1c levels in diabetic group
      confirmed a positive metabolic response to non-surgical periodontal treatment.
      CONCLUSION: With this study, we conclude that there is a definite reduction in
      HbA1c level in diabetic patients after conventional non-surgical periodontal
      treatment.

PMID- 22628958
TI  - Is there a relationship between periodontitis and rheumatoid arthritis?
AB  - BACKGROUND: Growth of scientific evidence suggests an exquisite association
      between oral infection and systemic diseases. Though etiologies of periodontitis
      and rheumatoid arthritis (RA) are separate, their underlying pathological
      processes are sufficient to warrant consideration of hypothesis that individuals
      at risk of developing RA may also be at the risk of developing periodontitis and
      vice versa. MATERIALS AND METHODS: To test their relationship, a study was
      carried out on 80 individuals. Part A: Forty subjects having rheumatoid arthritis
      (RA group) were compared to 40 controls without arthritis (NRA group). Their
      periodontal indices rheumatoid arthritis clinical laboratory parameters were also
      correlated with periodontitis in group. Part B: Omplete periodontal treatment was
      done for 10 patients of group suffering from periodontitis. All parameters of
      periodontal indices were measured pre-operatively and weeks after completion of
      periodontal treatment. RESULTS: (1) There was high prevalence of mild (12.5%) to
      moderate (75%) periodontitis in group. (2) Extent severity of periodontal disease
      rheumatoid arthritis were positively correlated. (3) Statistically significant
      differences were present in periodontal parameters of RA group compared to NRA
      group. (4) There was statistically, significant reduction in parameters
      postoperatively with concomitant decrease in periodontal parameters in RA group.
      CONCLUSION: Thus, an association exists between periodontal disease with an
      underlying dysregulation of the molecular pathways in the inflammatory response.
      Also, there are significant management implications in the future as new host
      modifying medications are developed.

PMID- 22628959
TI  - Association between alveolar bone loss and serum C-reactive protein levels in
      aggressive and chronic periodontitis patients.
AB  - BACKGROUND: C-reactive protein (CRP) is an acute phase reactant that is produced
      in response to diverse inflammatory stimuli, and is known predictor of
      cardiovascular disease risk. Aggressive and chronic periodontitis are two main
      forms of periodontal disease, which differ mainly in the method of disease
      progression. This study aims at determining and comparing the relative levels of
      serum CRP and alveolar bone loss in aggressive and chronic periodontitis
      patients. MATERIALS AND METHODS: A total of 45 subjects, which were divided into
      3 groups diagnosed as having generalized aggressive periodontitis (GAP), chronic
      generalized periodontitis (CGP) and non-periodontitis controls (NP), were
      selected for the study. Venous blood samples were collected for quantitative CRP
      analysis using Turbidimetric immunoassay. Alveolar bone loss (ABL) was measured
      at proximal sites of posterior teeth on a panoramic radiograph. The relationship
      between the mean ratio of ABL to root length and serum CRP levels was
      statistically analyzed using Student unpaired t-test, analysis of variance
      (ANOVA) and Pearson's correlation coefficient. RESULTS: Mean CRP levels were
      significantly greater in both GAP (7.49+/-2.31 mg/l) and CGP (4.88+/-1.80 mg/l)
      groups as compared to NP (0.68+/-0.23 mg/l) with P value <0.0001. The mean value
      of ABL (%) was 31.58 in CGP group and 36.77 in the GAP group, the difference
      being statistically significant (P=0.0079). Correlation coefficient between CRP
      and ABL is 0.9310 in CGP, and 0.9252 in GAP, which indicates a positive
      correlation between both variables. CONCLUSION: Both forms of periodontitis are
      associated with increased systemic inflammatory response with aggressiveness of
      disease progression determining the degree of response.

PMID- 22628960
TI  - Are lipid profiles true surrogate biomarkers of coronary heart disease in
      periodontitis patients?: A case-control study in a south Indian population.
AB  - BACKGROUND: There is abundant literature delving into whether periodontal
      infection contributes to atherosclerosis. However, whether periodontitis is a
      definite risk factor for atherosclerosis still remains empirical, with no
      systematic reviews or longitudinal studies to confirm this hypothesis. The
      prevalence of periodontitis and coronary artery disease also varies among racial
      and ethnic groups based on various factors such as diet, lifestyle, and genetic
      predisposition. This study was designed in a south Indian population with the aim
      of assessing and correlating the lipid levels (a surrogate biomarker for coronary
      heart disease) in patients with periodontitis and health. AIMS: (1) To assess the
      levels of total cholesterol, low density lipoproteins (LDL), high density
      lipoproteins (HDL), and triglycerides in periodontal disease, and health in a
      south Indian population. (2) To assess associations between elevated lipid
      profiles and periodontal disease. MATERIALS AND METHODS: This case control study
      included 60 individuals. Blood sampling for lipid levels and periodontal
      examination were performed for each study group. STATISTICAL ANALYSIS:
      Appropriate statistical tools like Chi-square (P<0.05) and student's "t" test
      were used. The lipid levels were separately regressed using logistic regression
      to determine any association with periodontitis cases. RESULTS: The differences
      between the mean lipid levels of cases and controls were not statistically
      significant (P>0.05) after eliminating confounding factors. Odds Ratio=(Total
      cholesterol (1.005), HDL (0.971), LDL (1.006), VLDL (0.997), CHO-HDL (1.358), TGL
      (1.007), LDL-HDL (1.180)). The odds ratio stated that there is no significant
      relation between the lipid levels and periodontal condition. The above findings
      confirm that there is still no concrete evidence which determines if
      periodontitis is an independent risk factor for atherosclerotic cardiovascular
      disease. Future periodontal interventional studies and assessment of genetic
      markers can ascertain the validity of this hypothesis. CONCLUSION: There is no
      association among periodontal disease and the levels of total cholesterol, LDL,
      HDL, and triglycerides.

PMID- 22628962
TI  - A comparative evaluation of atrigel delivery system (10% doxycycline hyclate)
      Atridox with scaling and root planing and combination therapy in treatment of
      periodontitis: A clinical study.
AB  - BACKGROUND: Local delivery of antimicrobial has resulted in good clinical outcome
      along with scaling and root planing. The present study is carried out to evaluate
      and compare the efficacy of local delivery of 10% doxycycline hyclate in adjunct
      to scaling and root planing in the treatment of periodontitis. MATERIALS AND
      METHODS: A randomized crossover split mouth design was performed, a total number
      of 130 sites from 4 patients, 63 sites from patients with aggressive
      periodontitis and 67 sites from chronic periodontitis patients were selected and
      divided into scaling and root planing (SRP) group, SRP and doxycycline group and
      doxycycline alone group. Clinical parameters viz. plaque index, modified gingival
      index, bleeding index, clinical attachment level (CAL), and sub gingival
      temperature were evaluated on day 0, 15(th), 45(th), and 90(th) day. CAL
      recording was performed only on day 0 and 90(th) day. RESULTS: In 90 days study,
      all the three groups showed significant reduction in clinical parameters. But on
      comparison, SRP and doxycycline group showed better results than doxycycline
      alone group and SRP alone group. CONCLUSION: The results of this study
      demonstrated that doxycycline hyclate 10% gel (Atridox) is as effective as SRP in
      reducing the clinical signs of periodontitis.

PMID- 22628961
TI  - Assessment of periodontal health status in patients undergoing renal dialysis: A
      descriptive, cross-sectional study.
AB  - OBJECTIVE: An inter-relationship between periodontal disease and systemic health
      has been suspected for centuries, but evidence to explain the connection has only
      been elucidated in the past few decades. Among the systemic diseases, end stage
      renal disease has been shown to affect not only the general health of the patient
      but also oral and periodontal health. This study was undertaken to gain an
      insight into whether duration of dialysis therapy influences the oral and
      periodontal health of these patients and also to see if these parameters reflect
      their biochemical values. MATERIALS AND METHODS: The study was conducted on 75
      patients undergoing dialysis and a control group of 25 subjects. The study group
      was divided into three subgroups depending upon the duration of dialysis. Oral
      hygiene and periodontal disease status were measured by Simplified Oral Hygiene
      Index by Greene and Vermillion and Periodontal Disease Index by Ram-fjord.
      Biochemical parameters measured were blood urea nitrogen and salivary urea
      levels. Comparison of these parameters was made between the study and control
      groups through analysis of variance (ANOVA) and student's t-test. RESULTS:
      Prevalence of periodontal disease was evident in the dialysis group. Oral hygiene
      status was poor in comparison with the control group. Clinical and biochemical
      parameters showed statistically significant difference between the groups rather
      than within the groups. CONCLUSION: Oral and periodontal health appeared to be
      compromised. Their deteriorating general health is anticipated to cause
      negligence towards oral health care. This population needs comprehensive oral and
      periodontal care right from the diagnosis of chronic renal failure. There exists
      a need for communication between nephrologists and oral health care
      professionals. Longitudinal studies warranted in this regard.

PMID- 22628963
TI  - The effect of platelet derived growth factor-AB on periodontal ligament
      fibroblasts: An in vitro study.
AB  - BACKGROUND AND OBJECTIVES: Traditional methods of periodontal therapy produce
      results in healing of tissues by repair; however, what we require is regeneration
      of the lost tissues. The periodontal ligament (PDL) cells appear to be important
      in periodontal wound healing. Platelet derived growth factor (PDGF), a potent
      mitogen and useful mediator for wound healing, has been extensively studied in
      periodontal regeneration. This in vitro study was designed to evaluate the effect
      of PDGF-AB on human PDL fibroblasts (hPDLF) at 50, 100 and 150 ng/ml dosages at
      24, 48 and 72 hours time duration. MATERIALS AND METHODS: Tissue explants from
      three different patients were harvested from the roots of freshly extracted,
      uninfected and impacted third molars. The cells cultured from all samples were
      divided into 4 groups: Group-1 was the control group, and the experimental groups
      were designated as Group-2, Group-3 and Group-4, to test the effect of PDGF-AB at
      50, 100 and 150 ng/ml by proliferation assay carried out at 24, 48 and 72 hours.
      RESULTS: The results revealed maximum mitogenic response of PDL cells at 100
      ng/ml and at 48 hours, suggesting that the mitogenic response of PDGF-AB is both,
      time and dose dependent. CONCLUSIONS: The results of this in vitro study suggest
      that PDGF has maximum mitogenic response on hPDLF at 48 hours and for 100 ng
      dose. However for clinical application, randomized controlled clinical trials are
      required to substantiate the results of this in vitro study.

PMID- 22628964
TI  - A study to assess and compare the peripheral blood neutrophil chemotaxis in
      smokers and non smokers with healthy periodontium, gingivitis, and chronic
      periodontitis.
AB  - BACKGROUND: Chronic periodontitis is the inflammation within the supporting
      tissues of the teeth resulting in attachment loss and bone loss. There are
      certain environmental factors such as smoking that can modify the host response
      to plaque organisms; hence can account for the aggressive progression of the
      disease. Smokers show a decreased expression of clinical inflammation even in the
      presence of abundant plaque accumulation. Neutrophils are the predominant host
      defense cells which protect the periodontal tissues from plaque organisms,
      deficiencies of neutrophil function, such as chemotaxis and phagocytosis, often
      result in increased susceptibility to periodontitis. Smoking can induce
      alteration in the neutrophil function; therefore, it is of importance to know the
      changes caused by smoking on neutrophil chemotaxis. This study will provide an
      essential basis for evaluating the role of nicotine in pathogenesis of
      periodontal disease by assessing the neutrophil activity. MATERIALS AND METHODS:
      A total of 60 smokers and 60 non smokers were examined for this study. Both the
      groups included 20 subjects with gingivitis, periodontitis, and healthy
      periodontium. The periodontal status of the study subjects were assessed by
      gingival index, Russels periodontal index, sulcus bleeding index, and clinical
      attachment level. The blood sample was taken from each individual for the
      chemotactic analysis using agarose method. RESULTS: In this study, there was a
      significant decrease in the neutrophil chemotaxis in smokers with gingivitis,
      periodontitis, and healthy periodontium, compared to non smokers with similar
      findings. CONCLUSION: Delayed neutrophil chemotaxis was found in smokers compared
      to non smokers with same periodontal status.

PMID- 22628965
TI  - Study of neutrophils isolated from peripheral blood of patients suffering from
      aggressive periodontitis at the cellular level: Receptors and cytoskeletal
      reorganization.
AB  - BACKGROUND: Aggressive periodontitis (AgP) has been associated with
      polymorphonuclear leukocyte's (PMNL) dysfunction and periodontal pathogens
      possess variety of virulence factors that can impair PMNL's function. This study
      investigated the possible association between defective neutrophil adhesion and
      beta(2) -integrin expression and defective neutrophil migration and actin
      polymerization level in the peripheral blood of neutrophils from the patients
      with AgP. MATERIALS AND METHODS: A total of 30 individuals both male and female,
      age ranges between 13 - 48 years, were included in the study. Healthy controls
      (group I, n=10), chronic periodontitis (ChP) (group II, n=10), and AgP (group
      III, n=10), all without any systemic diseases and non-smokers, were recruited.
      Peripheral blood samples were taken and beta(2) -integrin expression and actin
      polymerization levels were estimated by using fluorescence activated cell sorter
      analysis. RESULTS: In AgP cases, both average values (beta(2) -integrin and actin
      level) were significantly less than that of normal subjects (<0.001). But for ChP
      cases, only the average value of actin level is significantly lower than that of
      normal subjects (<0.025). CONCLUSION: Lower beta(2) -integrin expression in the
      AgP cases signifies lower neutrophil adhesion in AgP cases than normal, and the
      lower average value of actin polymerization for the AgP cases suggest lower
      migration capacity of neutrophils in AgP cases than normal.

PMID- 22628966
TI  - Relationship between Gram negative enteric rods, Aggregatibacter
      actinomycetemcomitans, and clinical parameters in periodontal disease.
AB  - BACKGROUND: The association between Gram negative enteric rods and
      Aggregatibacter actinomycetemcomitans in periodontal diseases has received little
      attention in the literature. The objective of this study was to explore the
      relationship between these organisms and clinical parameters of periodontal
      disease. MATERIALS AND METHODS: Clinical parameters and occurrence of Gram
      negative enteric rods and A. actinomycetemcomitans were examined in 76 patients
      with chronic periodontitis. Chi-square and Mann-Whitney tests were used to
      determine differences in clinical variables versus the presence or absence of
      both microorganisms. Correlation among both organisms and clinical data were
      determined using Spearman rank correlation coefficient. RESULTS: Gram-negative
      enteric rods and A. actinomycetemcomitans were detected in 20 (26.3%) and 18
      (23.7%) individuals, respectively. A total of 14 (18.4%) patients harbored both
      microorganisms studied. There were significantly positive correlations between
      enteric rods and presence of A. actinomycetemcomitans (r=0.652, P<0.0001). Both
      microorganisms were significant and positively correlated with probing depth
      (PD), clinical attachment level, and bleeding on probing (P<0.0001). The mean PD
      (mm) of the sampled sites was significantly deeper in patients with presence of
      A. actinomycetemcomitans and Gram-negative enteric rods. CONCLUSION: The results
      of the present study suggest a strong positive correlation between Gram-negative
      enteric rods and A. actinomycetemcomitans in the population studied. This finding
      must be taken into account when considering the best therapeutic approach,
      including the utilization of antimicrobials. The adverse clinical outcomes
      observed in presence of these microorganisms could have implications in the
      pathogenesis of periodontal disease and a possible impact on outcomes after
      treatment.

PMID- 22628967
TI  - EDTA-S: A novel root conditioning agent.
AB  - BACKGROUND: To evaluate the efficacy of 15% ethylenediaminetetraacetic acid
      (EDTA)-S (EDTA with soft soap) preparation for the removal of smear layer at
      human root surfaces. MATERIALS AND METHODS: Twenty teeth indicated for extraction
      due to periodontal disease were sectioned using high speed cylindrical bur under
      copious irrigation. The root surfaces were instrumented with Gracey 7-8 curette
      (Hu-Friedy), 12 times to induce an "experimental smear layer". Following root
      planning, the root surface was cut using diamond disc and separated from the
      crown. Samples were randomly distributed into five groups. One group was control,
      saline and test groups were EDTA 15% alone, by active and passive applications
      (groups 2 and 3), and EDTA 15%+soft soap, by active and passive applications
      (groups 4 and 5). Specimens were then subjected to scanning electron microscope
      study. Smear layer removal was evaluated according to Sampaio et al., index.
      RESULTS: EDTA-S removed the smear layer better than plain EDTA and the control
      group, while active application of the root conditioning agent had significant
      difference than the passive application of the agent. CONCLUSION: EDTA-S has
      favorable benefits over EDTA alone, and active application is better in
      comparison with passive application of root conditioning agent. CLINICAL
      RELEVANCE: Removal of smear layer has been considered as an important step in
      periodontal regenerative therapy. Scaling and root planning alone with saline
      irrigation does not remove the smear layer. EDTA is a commonly used root
      conditioning agent in periodontal therapy. The addition of a detergent to EDTA
      proved to remove smear layer more efficiently than EDTA alone.

PMID- 22628968
TI  - Determination of thickness of palatal mucosa.
AB  - BACKGROUND: The palatal masticatory mucosa is widely used as a donor material in
      periodontal plastic surgery. The thickness of graft tissue is an important factor
      for the graft survival. The purpose of this study was to determine the thickness
      of palatal mucosa by a bone sounding technique. The association of age and gender
      with the thickness of palatal mucosa was also examined. MATERIALS AND METHODS:
      Twenty four healthy subjects had participated in the study. The younger age group
      of 16-30 years consisted of 12 subjects of 7 females and 5 males, and the older
      age group of 31-54 years consisted of 12 subjects, of 5 females and 7 males. A
      bone sounding method using a periodontal probe was done to assess the thickness
      of palatal mucosa at 15 measurement sites defined according to the gingival
      margin and palatal line. Mann-Whitney test was used to determine the difference
      in mucosal thickness between both the groups. RESULTS: The younger age group had
      thinner mucosa ranged from 2 to 3.1 mm in thickness than the older age group
      which ranged from 3.2 to 3.7 mm. In the same age group, females had thinner
      mucosa than males in the same age group. The mean thickness of palatal
      masticatory mucosa ranged from 2.5 to 3.7 mm. CONCLUSION: The younger subjects
      had thinner mucosa than older subjects. The canine and premolar areas appeared to
      be the most appropriate donor site for grafting procedures.

PMID- 22628969
TI  - Clinical effect of miswak as an adjunct to tooth brushing on gingivitis.
AB  - BACKGROUND: The aim of the study was to clinically evaluate the effect of miswak
      as an adjunct to tooth brushing on plaque levels and gingival health in subjects
      diagnosed with mild to moderate chronic generalized marginal gingivitis in
      comparison with those of toothbrush users. MATERIALS AND METHODS: The study
      comprised of 30 systemically healthy subjects, aged 18-35 years diagnosed with
      mild to moderate gingivitis. The study was designed as a randomized, single
      blind, parallel-armed study. Subjects were randomly divided into three groups.
      Group A (toothbrush users), group B (toothbrush and miswak users), and group C
      (miswak users). Subjects were advised to use toothbrush, miswak, or both, three
      times daily depending on their respective allocations. Gingival index according
      to Loe and Silness, Plaque index, according to Turesky modified Quigley-Hein
      plaque index, and the digital photographs of the total labial surfaces of the
      teeth were taken for image analysis. Recording of data were done at baseline,
      2(nd), 4(th), 6(th), and 8(th) week time intervals. Obtained data were analyzed
      using repeated measure ANOVA and student t test (independent samples). RESULTS:
      Group B showed statistically significant (P<0.0001) decrease in plaque score and
      gingival score compared to group A and group C, respectively, from 2(nd) to 8(th)
      week, whereas no statistical significant difference was found in plaque score,
      when group A was compared with group C (P>0.05) from 2(nd) to 4(th) week. Further
      at the 6(th) and 8(th) week, there was significant difference (P<0.05) in plaque
      score between group A and group C. The difference in gingival score was not
      significant (P<0.05), when group A was compared with group C on all the indicated
      time intervals. CONCLUSION: Results showed significant improvement in plaque
      score and gingival health when miswak was used as an adjunct to tooth brushing.

PMID- 22628970
TI  - Evaluation of immediately loaded dental implants bioactivated with platelet-rich
      plasma placed in the mandibular posterior region: A clinico-radiographic study.
AB  - BACKGROUND AND OBJECTIVES: The purpose of the present study was to clinically and
      radiographically assess the soft and hard tissue changes around the immediately
      loaded single tooth implants bioactivated with platelet-rich plasma (PRP), placed
      in the mandibular posterior region. MATERIALS AND METHODS: A total of 11 patients
      having single tooth edentulous space in the mandibular posterior region were
      selected. An endosseous implant was placed after clinical and radiographic
      examination in each selected site using single stage surgical approach. The
      patients were followed up at 3, 6, 9, and at 12 months of post implant insertion.
      The patients were subjected to recording of clinical parameters like modified
      plaque index, modified gingival index, probing depth, and clinical implant
      mobility scale. Radiographs made at different intervals were subjected to
      assessment of bone level mesial and distal to each implant using computer
      assisted image analysis. RESULTS: Scores for clinical parameters were minimal and
      comparable. The probing depth around the implant was measured during the follow
      up period and the changes observed were statistically non-significant. None of
      the implants were clinically mobile during the follow-up period.
      Radiographically, the peri-implant bone resorption both on mesial and distal
      sides was within normal limit after one year of immediate loading. Finally, the
      overall success rate for the immediately loaded bioactivated implant placed in
      the mandibular posterior region was recorded as 100%. INTERPRETATION AND
      CONCLUSION: The use of platelet-rich plasma may lead to improved early bone
      apposition around the implant; and thus, results in increased rate of
      osseointegration. Single stage implant procedure with the adjunctive use of PRP
      enhances the ability of peri-implant healing tissue to create favorable soft and
      hard tissue relationships. It also gives the added advantage of psychological
      boost for the patient by getting fixed replacement of tooth within a short time
      period.

PMID- 22628971
TI  - Ultra-morphology of root surface subsequent to periodontal instrumentation: A
      scanning electron microscope study.
AB  - BACKGROUND: The aim of this study was to compare root surface characteristic
      following root planing with various hand and power driven instruments. MATERIALS
      AND METHODS: A total of 20 single rooted teeth were used in this study, of which
      two specimens were used as control (no instrumentation done) and remaining 18
      specimens were equally divided into three groups. Specimens from each group were
      then subjected to root planing by one of the following instruments: (1) a Gracey
      curette (2) Ultrasonic tip and (3) a Rotary bur. In each case, the time required
      for scaling and root planing was measured. After treatment, the specimens were
      observed under scanning electron microscope and surface roughness was measured by
      using Roughness and loss of tooth substance index (RLTSI). RESULTS: The mean
      RLTSI scores for Gracey curette, ultrasonic and rotary instrument group were 2.5,
      2.0 and 0.667 respectively. The mean scores of time spent for scaling and root
      planing by Gracey curette, ultrasonic and rotary instrument group in seconds were
      42.50, 35.83 and 54.50. CONCLUSION: All the three instruments namely Gracey
      curette, Ultrasonic tip and Rotary bur were effective in mechanical debridement
      of root surface. The results favoured the use of rotary instruments for root
      planing to achieve smooth clean root surface; however, the use of rotary
      instrument was more time consuming which might limit its use in clinical
      practice.

PMID- 22628972
TI  - Smoking swings of gingival crevicular fluid secretion.
AB  - OBJECTIVE: Smoking is detrimental to gingival and periodontal health. It has been
      reported to produce changes in gingival crevicular fluid (GCF) flow, but the
      cumulative effects of smoking on GCF have not been studied till date. The present
      study was designed to discover and evaluate transitional dynamics, if any, in GCF
      flow just immediately before and after smoking. MATERIALS AND METHODS: The study
      comprised age- and gender-matched 20 male subjects. Half of the study population
      was constituted by non-smokers who comprised the control group and the remaining
      half of the study population was chronic smokers constituting the test group. The
      GCF samples were collected using the micropipettes before smoking, immediately
      after, and 10 min after smoking for the test group and during similar timings for
      the control group. RESULTS AND CONCLUSION: The study reveals an overall low GCF
      volume in smokers than in non-smokers. More interestingly, a transitional
      decrease immediately after smoking is followed by a marked increase in GCF volume
      10 min after smoking.

PMID- 22628973
TI  - Gingival squamous cell carcinoma: A diagnostic impediment.
AB  - Oral squamous cell carcinomas represent 3% of cancers in men and 2% of cancers in
      women. More than 90% of oral cancer occurs in people older than 45 years Lesions
      of gingiva account for approximately 10% of the oral squamous cell carcinomas and
      may present clinically as an area of ulceration, exophytic mass, or red/white
      speckled patches. The proximity to the underlying periosteum may invite early
      bone invasion. Carcinoma of gingiva constitutes an extremely important group of
      neoplasms as the lesion frequently mimics the reactive and inflammatory
      conditions affecting the periodontium, delaying the diagnosis and making the
      prognosis of the patient poorer. A rare case of gingival squamous cell carcinoma
      has been reported here, in a 40 Year old male patient. Careful recording of the
      case history and results of clinical examination, radiographic, and laboratory
      investigations, along with a critical review of similar conditions led to the
      diagnosis, and treatment was initiated.

PMID- 22628974
TI  - Use of platelet rich fibrin in a fenestration defect around an implant.
AB  - Guided bone regeneration (GBR) in implant therapy is especially useful for
      implant placement with dehiscence defects or fenestration defects. In alveolar
      ridges with marked facial/buccal depressions or in knifeedge alveolar crests, the
      position and direction of fixture placement is restricted. Improvement of
      alveolar ridge morphology becomes possible with GBR. This article describes a
      case in which the fenestration defect around an implant was treated by the
      application of platelet rich fibrin, a second generation platelet concentrate
      along with bone graft, and guided tissue regeneration membrane.

PMID- 22628975
TI  - Recurrent periodontal abscess associated with "teeth as a tool".
AB  - We report an unusual case of recurrent periodontal abscess in a 31-year-old male
      electrician due to his habit of using his teeth as a tool for stripping
      electrical wires. The patient was not aware of the consequences of this habit.
      Clinically, there was presence of moderate depth of periodontal pocket around the
      tooth and, radiographically, there was a vertical defect mesial to the involved
      teeth. The patient was educated about the consequences of his habit and surgical
      treatment was undertaken. A papilla preservation flap with regenerative
      periodontal surgical procedure was done, orthodontic and restorative treatment
      was planned at the follow-up. This case highlights the importance of eliciting a
      proper and complete personal history, including occupational details. In our
      patient these details helped us correlate the destruction of the periodontium to
      the unusual etiology.

PMID- 22628976
TI  - Plasma cell gingivitis associated with cheilitis: A diagnostic dilemma!
AB  - Plasma cell gingivitis is a rare condition characterized by diffuse and massive
      infiltration of plasma cells into the sub-epithelial connective tissue.
      Clinically, it appears as a diffuse reddening and edematous swelling of the
      gingiva with a sharp demarcation along the mucogingival border. Though considered
      as a hypersensitive reaction to an allergen, the etiology of this bizarre
      condition is still not properly understood. Here, we present an interesting case
      of plasma cell gingivitis associated with an enlarged and fissured upper lip,
      which is quite a rarity. The condition was diagnosed based on clinical and
      histopathologic findings and treated by gingivectomy. The associated cheilitis
      has dramatically reduced after treatment of the gingival lesion.

PMID- 22628977
TI  - Osseous choristoma of the periodontium.
AB  - Osseous choristoma is a rare, benign lesion of the oral cavity occurring usually
      on the tongue. It appears as a tumorous mass of normal bony structure with mature
      cells in an ectopic position. Some lesions represent developmental malformations,
      whereas others may be reactive lesions, after trauma or chronic irritation. This
      is the first ever reported case of an osseous choristoma of the periodontium in
      the lingual aspect of posterior mandible.

PMID- 22628978
TI  - Periodontal ligament distraction: A simplified approach for rapid canine
      retraction.
AB  - Distraction osteogenesis is a method of inducing new bone formation by applying
      mechanical strains on preexisting bone. The process of osteogenesis in the
      periodontal ligament during orthodontic tooth movement is similar to the
      osteogenesis in the midpalatal suture during rapid palatal expansion. A new
      concept of "distracting the periodontal ligament" is proposed to elicit rapid
      canine retraction in two weeks. At the time of first premolar extraction, the
      interseptal bone distal to the canine was undermined with a bone bur, grooving
      vertically inside the extraction socket along the buccal and lingual sides and
      extending obliquely toward the socket base. Then, a tooth-borne, custom-made,
      intraoral distraction device was placed to distract the canine distally into the
      extraction space. It was activated 0.5 mm/day, immediately after the extraction.
      Canine was distracted 6.5 mm into the extraction space within two weeks.

PMID- 22628979
TI  - Discoid lupus erythematosus involving gingiva.
AB  - Desquamative gingival lesions are non-plaque induced inflammatory gingival
      lesions. It is a clinical description and not a diagnosis. These desquamative
      lesions represent oral manifestations of various dermatoses. Discoid lupus
      erythematosus is one of the rare dermatoses which show desquamative lesions as
      oral manifestations. This article presents a rare case report of discoid lupus
      erythematosus with oral lesions involving gingiva of a 66-year-old female
      patient.

PMID- 22628980
TI  - Periodontal management in Paget's disease: Case presentation and a brief review
      of literature.
AB  - Paget's disease of bone is a common condition characterized by increased and
      disorganized bone turnover which can affect one or several bones throughout the
      skeleton. These abnormalities disrupt normal bone architecture and lead to
      various complications such as bone pain, osteoarthritis, pathological fracture,
      bone deformity, deafness, and nerve compression syndromes. Genetic factors and
      environmental factors like paramyxovirus infection have been implicated in
      etiology. This is a case report of a patient who presented with Paget's disease
      and the periodontal surgical management, after the pretreatment was employed with
      diagnostic procedures like computed tomography and serum alkaline phosphatase
      tests.

PMID- 22628981
TI  - Peripheral osteoma of the hard palate.
AB  - Osteomas are benign slow growing, osteogenic lesions which may arise from
      proliferation of either cancellous or compact bone. They are usually sessile
      tumours composed of dense sclerotic, well formed bone projecting out from the
      cortical surface, most often of the skull and facial bones. This paper reports a
      case of a peripheral osteoma in the hard palate of a 45-year-old man, which was
      treated by periodontal flap surgery with surgical excision of the bony lesion.
      Peripheral osteomas of jaw bone are uncommon and usually associated with
      Gardner's syndrome. Histological examination confirmed the clinical impression of
      a peripheral osteoma. Patient was reviewed after one year and was asymptomatic
      with no recurrence of the lesion.

PMID- 22628982
TI  - Achondroplasia and periodontal disease.
AB  - Achondroplasia is a non-lethal form of chondrodysplasia. It is a disturbance of
      endochondral bone formation which results in characteristic dwarfism. It is
      transmitted as an autosomal dominant trait, with complete penetrance. De novo
      mutations cause up to 90% of cases. The mutation rate is estimated to be 0.000014
      per gamete per generation. It is a rare disorder with a prevalence of 1:10,000 to
      1:50,000 births worldwide. A young female patient suffering from achondroplasia
      reported with oral manifestations showing features of periodontitis, hypoplasia
      of the mid-face, deep periodontal pockets, and mobility of teeth. This case
      report highlights this rare anomaly and its oral manifestations.

PMID- 22628983
TI  - Can beverages grow hair on bald heads?

PMID- 22628985
TI  - Value of trichoscopy versus trichogram for diagnosis of female androgenetic
      alopecia.
AB  - BACKGROUND: Female androgenetic alopecia (FAGA) is a frequent cause of hair loss
      in women. Standard diagnostic methods are clinical inspection, pull test, and
      trichogram. It has been suggested that scalp dermoscopy (trichoscopy) revealing
      diversity of hair shaft diameter >20% is diagnostic of FAGA. OBJECTIVE: To
      evaluate the value of trichoscopy as compared to the trichogram for the diagnosis
      of FAGA. PATIENTS AND METHODS: Retrospective case study of 162 women with the
      complaint of hair loss who underwent trichoscopic examination and trichograms.
      RESULTS: Of all women diagnosed FAGA (55%), 62% were diagnosed by trichogram, 72%
      by trichoscopy with a cut-off point of 20%, and 100% irrespective of the degree
      of diversity of hair shaft diameter. CONCLUSIONS: Trichoscopy is a valuable and
      superior method to the trichogram for diagnosis of FAGA, especially in early
      cases, with the highest yield irrespective of the suggested cut-off of 20%
      diversity of hair shaft.

PMID- 22628987
TI  - Brooke-spiegler syndrome: a rare entity.
AB  - Brooke-Spiegler syndrome (BSS) is a rare autosomal dominant disorder
      characterized by the presence of various adnexal tumors including multiple
      cylindromas, trichoepitheliomas and spiradenomas. A 35-year-old female presented
      with multiple asymptomatic nodular lesions over face and scalp since the age of 5
      years. There were no complaints suggestive of systemic involvement. Her son,
      elder sister, younger sister, father, father's sister, and grandmother had
      history of similar lesions. On examination, there were multiple asymptomatic skin
      colored firm papulonodular lesions measuring from 2 to 8 mm in diameter, with
      smooth surface mainly affecting central part of face. Scalp showed pinkish, firm,
      smooth-surfaced, dome-shaped nodules measuring about 1 to 3 cm in size.
      Histopathological examination was consistent with trichoepitheliomas for the
      facial lesions and cylindromas for the scalp lesions. The diagnosis of BSS was
      thus confirmed.

PMID- 22628986
TI  - Female pattern hair loss: clinico-laboratory findings and trichoscopy depending
      on disease severity.
AB  - BACKGROUND: Female pattern hair loss (FPHL) is a progressive hair loss disorder
      with unclear triggering and supporting factors. Trichoscopic features of each
      stage of FPHL have not been specifically elaborated previously. AIMS: To analyze
      characteristics and investigate associations of clinico-laboratory and
      trichoscopic features of female patients in regard to the severity of hair loss
      in FPHL and to facilitate its diagnosis using noninvasive scalp dermoscopy
      (trichoscopy) in Fitzpatrick skin type III patients. MATERIALS AND METHODS:
      Clinico-laboratory and trichoscopic data from 60 patients with FPHL were analyzed
      using Spearman's correlation test. RESULTS: Patients had mean age of 34.4+/-10.6
      years and mean duration of hair loss of 4.49+/-3.76 years. Of all, 45% (27/60)
      had a family history of pattern hair loss (PHL) and had an earlier onset of hair
      loss. Stage of hair loss positively correlated with duration and age at
      presentation. No association was found between the severity of FPHL and
      laboratory values including anemic and gonadal hormone profiles. Characteristic
      trichoscopic features (at 10-fold magnification) of FPHL were peripilar signs
      (PPS) (brown, BPPS and white, WPPS), white dots, scalp pigmentation, and focal
      atrichia. WPPS, scalp pigmentation, and focal atrichia positively correlated with
      the stage and duration of hair loss. CONCLUSIONS: Family history of PHL causes an
      earlier onset of hair loss but does not influence its course or severity. The
      latter is also not affected by abnormal anemic profile or hormonal levels. PPS,
      scalp pigmentation, focal atrichia, and white dots are characteristic of PHL.
      WPPS, scalp pigmentation, and focal atrichia reflect advanced PHL.

PMID- 22628984
TI  - Madarosis: a marker of many maladies.
AB  - Madarosis is a terminology that refers to loss of eyebrows or eyelashes. This
      clinical sign occurs in various diseases ranging from local dermatological
      disorders to complex systemic diseases. Madarosis can be scarring or non-scarring
      depending upon the etiology. Appropriate diagnosis is essential for management.
      Follicular unit transplantation has been found to be a useful method of treating
      scarring madarosis and the procedure relevant to eyebrow and eyelash
      reconstruction has been discussed. A useful clinical approach to madarosis has
      also been included for bedside diagnosis. The literature search was conducted
      with Pubmed, Medline, and Google scholar using the keywords madarosis, eyebrow
      loss, and eyelash loss for articles from 1960 to September 2011. Relevant
      material was also searched in textbooks and used wherever appropriate.

PMID- 22628988
TI  - Congenital hypotrichosis, eruptive milia, and palmoplantar pits: a case report
      with review of literature.
AB  - We report a ten-month-old male infant, presenting with congenital hypotrichosis
      of scalp, absence of eyebrows and eyelashes. He also had multiple milia over face
      and extremities along with palmoplantar pits. The infant was born to third degree
      consanguineous marriage. None of the family members had similar disease.
      Histopathology was consistent with milia. Based on these findings, a diagnosis of
      unclassified ectodermal dysplasia was made.

PMID- 22628989
TI  - Trichoscopy and histopathology of follicular keratotic plugs in scalp discoid
      lupus erythematosus.
AB  - Dermoscopy has become an integral part of diagnosing scalp disorders including
      discoid lupus erythematosus (DLE). Follicular keratotic plugs are a marker of DLE
      and correlate with the hyperkeratosis and plugging of the follicular ostia with
      keratotic material. They may be present in acute or chronic lesions and their
      presence alone or in conjunction with other described dermoscopic features can
      lead to timely diagnosis and initiation of treatment. We present three cases of
      scalp DLE and discuss the clinical, dermoscopic and histopathologic features.

PMID- 22628990
TI  - Habit reversal training for trichotillomania.
AB  - Trichotillomania is characterized by the repeated urge to pull out hair, leading
      to noticeable hair loss, distress, and social or functional impairment. Most of
      the cases present initially to dermatologists with complaints of loss of hair and
      is often confused with other dermatological conditions like alopecia areata,
      tinea capitis, traction alopecia, and loose anagen syndrome. It is a chronic
      condition and difficult to treat. No formal treatment algorithm is present for
      trichotillomania and no drug has been found to be universally effective. We
      present a case report of a 22-year-old single female diagnosed with
      trichotillomania, with complaints of recurrent hair pulling resulting in
      noticeable hair loss since the age of 8 years. She was treated with Habit
      Reversal Training with Stimulus Control over a period of 12 weeks and attained
      complete remission. The effectiveness of HRT plus for the treatment of
      Trichotillomania is ascertained.

PMID- 22628991
TI  - Woolly hair nevus: a rare entity.
AB  - Woolly hair nevus is a rare non-hereditary focal condition characterized by
      unruly and tightly coiled hair. It can appear in childhood or adolescence and may
      be associated with epidermal or melanocytic nevus. Patients presenting with
      woolly hair must be examined completely to rule out cardiofaciocutaneous and
      Noonan syndrome.

PMID- 22628992
TI  - Cerebriform plaque on the scalp.

PMID- 22628993
TI  - Threading: a timeless method for facial hair maintenance and potential
      complications.

PMID- 22628994
TI  - Tackling Chemotherapy-induced Alopecia.

PMID- 22628995
TI  - Significance of scraping scalp lesions in adults.

PMID- 22628996
TI  - Cosmetically disfiguring side effects of cyclosporine.

PMID- 22628997
TI  - Giant congenital triangular alopecia mimicking alopecia areata.

PMID- 22628998
TI  - Measuring the efficacy of antiretroviral therapy.

PMID- 22628999
TI  - Monilethrix: A New Family with the Novel Mutation in KRT81 Gene.

PMID- 22629000
TI  - Introducing medical humanities in the medical curriculum in Saudi Arabia: A
      pedagogical experiment.
AB  - In a marked shift from the modern positivist materialist philosophy that
      influenced medical education for more than a century, Western medical educators
      are now beginning to realize the significance of the spiritual element of human
      nature. Consensus is currently building up in Europe and North America on the
      need to give more emphasis to the study of humanities disciplines such as history
      of medicine, ethics, religion, philosophy, medically related poetry, literature,
      arts and medical sociology in medical colleges with the aim of allowing graduates
      to reach to the heart of human learning about meaning of life and death and to
      become kinder, more reflective practitioners. The medicine taught and practiced
      during the Islamic civilization era was a vivid example of the unity of the two
      components of medical knowledge: natural sciences and humanities. It was also a
      brilliant illustration of medical ethics driven by a divine moral code. This
      historical fact formed the foundation for the three medical humanities courses
      presented in this article reporting a pedagogical experiment in preparation for
      starting a humanities program in Alfaisal University Medical College in Riyadh.
      In a series of lectures alternating with interactive sessions, active learning
      strategies were employed in teaching a course on history of medicine during the
      Islamic era and another on Islamic medical ethics. Furthermore, a third course on
      medically relevant Arabic poetry was designed and prepared in a similar way. The
      end-of-the-course feedback comments reflected effectiveness of the courses and
      highlighted the importance of employing student-centered learning techniques in
      order to motivate medical students to become critical thinkers, problem solvers,
      life-long learners and self-learners.

PMID- 22629001
TI  - The influence of urine cytology on our practice.
AB  - OBJECTIVE: Bladder cancer is a common malignancy. It is ranked ninth among male
      population in Saudi Arabia. Urine cytology is used by some physicians routinely
      in the workup for diagnosis and follow-up of patients with urothelial cancer. Our
      objective is to determine whether urine cytology is still essential in the work
      up of suspected urothelial cancer patients and to measure its cost-effectiveness.
      MATERIALS AND METHODS: We reviewed all urine cytology reports that were performed
      over a period of five years from 2006 to 2010 in the International Medical Center
      in Jeddah, Saudi Arabia. The medical records of patients with cytology reports of
      both positive for malignant cells and atypical cells suspicious of malignancy
      were retrospectively, studied for age, sex, nationality, cystoscopic findings,
      imaging results, and total cost. RESULTS: A total of 563 urine cytology tests
      were done on 516 patients. Two patients were positive for malignant cell and 10
      showed atypical cells suspicious of malignancy. All 12 patients underwent imaging
      and/or cystoscopy as part of their complete work up for hematuria. The two
      patients with positive cytology had a cystoscopic confirmation of bladder tumor.
      In the 10 patients with atypical cells, bladder tumor was identified in seven
      using cystoscopy and/or imaging. The mean age was 54.6+/-16 year (range 15-95).
      The total cost was 140,750 SR (37,533 USD) for a yield of 0.3% positive results
      and 2% atypical cytology. CONCLUSION: Routine urine cytology did not affect the
      diagnostic strategy for urothelial cancer. It should be only used in selected
      patients.

PMID- 22629002
TI  - Results of low threshold to biopsy following high-intensity focused ultrasound
      for localized prostate cancer.
AB  - CONTEXT: There are different treatment options for localized prostate cancer. The
      success of high-intensity focused ultrasound (HIFU) is based largely on
      biochemical prostate specific antigen (PSA) results. AIMS: To evaluate the impact
      of using a low PSA threshold to perform prostate biopsies after HIFU in order to
      more accurately gauge treatment success. SETTINGS AND DESIGN: Eleven patients
      underwent HIFU at Sydney Adventist Hospital in Sydney, 10 as primary and 1 as
      salvage therapy [post external beam radiation therapy (EBRT)]. The median age was
      67 years (49-77 years). This was a prospective case series. MATERIALS AND
      METHODS: Between 2006 and 2008, the Sonoblate device was used. Prostate biopsies
      were 12-core biopsies performed under local anesthesia, if PSA was >=0.5 ng/mL or
      after two consecutive rises in PSA. The statistical analysis involved prospective
      data collection of results to calculate median and ranges. RESULTS: The median
      PSA at diagnosis was 6.7 ng/mL (5.7-10.8 ng/mL). The median follow-up was 16
      months (7-26 months). Nine men (82%) had post-HIFU biopsy. The median time to
      post-HIFU biopsy was 11.6 months (5-20 months), and all nine men had biopsy
      proven residual disease. CONCLUSIONS: A low threshold to re-biopsy post-HIFU
      reveals a high local failure rate of 82%. Oncological efficacy is questioned, and
      using high threshold to biopsy may therefore be overestimating the effectiveness
      of HIFU as a primary treatment for localized prostate cancer.

PMID- 22629003
TI  - Effects of melatonin on partial unilateral ureteral obstruction induced oxidative
      injury in rat kidney.
AB  - AIM: This experimental study was designed to produce ischemia-reperfusion injury
      in rat kidney by performing partial unilateral ureteral obstruction (PUUO) and
      investigated the effects of melatonin on the levels of oxidative injury
      parameters. MATERIALS AND METHODS: Twenty-four adult male rats were randomly
      divided into three groups as follows; control group (Group 1); only nephrectomy
      and blood (5 ml) drawn from vena cava inferior, PUUO group (Group 2); PUUO (10
      days)+ipsilateral nephrectomy after recovery of PUUO+blood from vena cava
      inferior VCI, melatonin treated group (Group 3); PUUO (10 days)+melatonin (1/2 hr
      before release, 50 mg/kg, ip)+ipsilateral nephrectomy after recovery of
      PUUO+blood from VCI. The left ureter was embedded into the psoas muscle to create
      PUUO. After 10 days, PUUO was recovered and ipsilateral nephrectomies were
      performed for biochemical analysis of superoxide dismutase (SOD), catalase (CAT),
      malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and protein carbonyl (PC)
      in the tissues and blood was drawn from inferior vena cava to study the same
      parameters in systemic circulation. The results were compared statistically.
      RESULTS: The blood levels of MDA, NO, and PC were increased in the PUUO group in
      comparison to the sham-operated group (P<0.05). Melatonin treatment reduced MDA,
      NO, and PC levels in blood after PUUO recovery, but statistically significance
      consisted only for MDA and NO (P<0.05). The antioxidant enzyme activities (SOD,
      GSH-Px) were increased in the PUUO group (P<0.05). Melatonin treatment reduced
      SOD and GSH-Px activities in comparison with the sham-operated control group
      (P<0.05). Similarly, renal tissue levels of MDA, NO, and PC were increased in the
      PUUO group in comparison with the sham-operated group (P<0.05). Melatonin
      treatment ameliorated MDA, NO, and PC levels in renal tissue after PUUO recovery
      only MDA was statistically significant (P<0.05). Antioxidant enzyme activities
      (SOD, CAT, and GSH-Px) were increased in the PUUO group. Melatonin treatment
      caused reduction in SOD, CAT, and GSH-Px activities in comparison to the sham
      operated control group (P<0.05). CONCLUSION: The results of this study showed
      that experimentally induced PUUO caused oxidative stress in rat kidney and
      melatonin treatment reduced oxidative stress and therefore may have a preventive
      effect on PUUO induced oxidative kidney damage in rats.

PMID- 22629004
TI  - Laparoscopic adrenalectomy: 10 years experience.
AB  - PURPOSE: Laparoscopic adrenalectomy is considered the standard technique for the
      surgical removal of the adrenal gland. Shorter length of stay, decrease in
      postoperative pain and reduced complication are all the advantages of the
      laparoscopic approach. This report is about a 10-year single experience with
      laparoscopic adrenalectomy. MATERIALS AND METHODS: A total of 34 lateral
      transperitonial laparoscopic adrenalectomies were performed. 24 right-sided
      lesions and 10 left-sided lesions were removed. The indications for surgery were
      aldosteronoma in 20 patients and nonfunctioning adenoma in 10 patients, and 1
      child underwent bilateral adrenalectomy for bilateral adrenal hyperplasia.
      RESULTS: All except one had successful laparoscopic adrenalectomy. Complication
      occurred in one patient who required open conversion because of bleeding. In
      addition, one patient suffered a pancreatic injury where the patient was managed
      conservatively. The average operative time was 2 hours and 30 minutes and the
      hospital stay was 2.5 days. CONCLUSION: Laparoscopic adrenalectomy is technically
      feasible and reproducible. Lateral transperitoneal approach offers advantages
      including better visibility and easy access to other organ systems. There is
      always a learning curve for the urological laproscopy.

PMID- 22629005
TI  - CA 19-9 as a serum marker in urothelial carcinoma.
AB  - INTRODUCTION: CA 19-9 is a carbohydrate antigen related to Lewis A blood group
      antigen. It is well-known marker for pancreatic carcinoma and is being
      investigated for other malignancies including carcinoma bladder. We evaluated the
      role of serum CA 19-9 as a tumor marker and correlated its level with tumor stage
      and grade. MATERIALS AND METHODS: Seventy-five patients with histologically
      proven urothelial carcinoma were included in this study as case and 25 healthy
      volunteers as control. Preoperative 5 ml blood sample was collected. Serum level
      of CA 19-9 was measured using solid-phase enzyme-linked immunosorbent assay kit.
      The value of CA19-9 was expressed in U/ml and 37 U/ml was taken as cut-off upper
      value of normal. RESULTS: The range of CA19-9 in patients of urothelial carcinoma
      was 2 to 122 U/ml with a mean of 26.33+/-29.28, while in control, it was 8.48+/
      5.01 U/ml (P<0.001). The sensitivity of CA19-9 was 29%. Serum CA19-9 was
      significantly elevated in invasive disease in comparison with superficial disease
      (47.17+/-34.43 vs 16.53+/-20.13) (P<0.001). Significantly high proportion of
      patients with invasive disease had value >=37 U/ml (14/24 [58.3%] vs 8/51
      [15.7%]) with P value <0.001. High proportion of high-grade tumor had raised
      value, 14/34 (41.25%); all patients with metastatic disease had value more than
      37 U/ml. CONCLUSIONS: Serum CA19-9 is a marker of aggressiveness of urothelial
      carcinoma and is almost invariably raised in patients with metastatic disease.
      Thus, it may be used as a prognostic marker but not as a screening tool due to
      its low sensitivity.

PMID- 22629006
TI  - Ureterovaginal fistulas: The role of endoscopy and a percutaneous approach.
AB  - PURPOSE: The aim of the study was to evaluate the minimal invasive approach and
      endourological techniques in managing the iatrogenic ureterovaginal fistula. The
      etiology and the diagnostic tools were also looked at. PATIENTS AND METHODS: A
      retrospective study was conducted on 20 patients with ureterovaginal fistulas.
      The main causes for these were gynecological and obstetrical procedures. In all
      cases, the diagnosis was based on clinical presentation, intravenous pyelography,
      and cystoscopy. Various therapeutic methods were used. Eleven patients were
      treated by the endoscopic placement of a ureteral stent and 13 patients
      (including four with failed initial ureteral stent insertion) received ureteral
      reimplantation. Of these, two patients were treated by the Boari flap method, six
      by Psoas hitch, four by simple ureteric reimplant, and one by
      transureteroureterostomy. RESULTS: Of the 11 patients treated by the endoscopic
      placement of a ureteral stent, 7 (64%) were successfully managed with this
      treatment alone. The remaining 4 (36%) also had open surgery. A total of 13
      patients (including the 4 initially treated with endoscopic placement) underwent
      successful ureteric reimplantation. Routine cystoscopy revealed that 2 of the 20
      patients (10%) had a concurrent vesicovaginal fistula. CONCLUSION: A
      ureterovaginal fistula is a rare but a relatively frequent complication of pelvic
      surgery. We recommend a minimal invasive approach including ureteric stent
      insertion as primary management and routine cystoscopy to rule out an association
      of a vesicovaginal fistula.

PMID- 22629007
TI  - Midureteric knotted stent removed by percutaneous access!
AB  - Indwelling ureteric stents are commonly used in the management of upper urinary
      tract obstruction. A rare complication is the knotting of an indwelling ureteric
      stent at its proximal coiled end. We present a case of a mid ureteric knotted
      stent that put the kidney at risk. Stent was extracted successfully by
      Percutaneous method, after failed minimally invasive methods.

PMID- 22629008
TI  - Commentary.

PMID- 22629009
TI  - Priapism, pomegranate juice, and sildenafil: Is there a connection?
AB  - We report the development of low flow priapism in three patients related to
      simultaneous consumption of sildenafil with pomegranate (Punica granatum) (POM)
      juice. There were no other concurrent diseases, intake of drugs, and chemicals or
      other risk factors in these patients. We want to create awareness among patients
      and practitioners for recognition and timely intervention. Probable mechanisms
      are highlighted.

PMID- 22629010
TI  - Management of pelvic lymphoceles following robot-assisted laparoscopic radical
      prostatectomy.
AB  - Pelvic lymphocele is a potential complication of radical prostatectomy. Although
      lymphoceles often regress spontaneously, many may progress, precipitate clinical
      symptoms, and ultimately require intervention. To date, the best treatment of
      pelvic lymphoceles has not yet been fully defined. However, laparoscopic
      marsupialization is a definitive and efficacious surgical alternative to
      percutaneous drainage. It is effective, results in minimal patient morbidity, and
      allows for rapid recovery. We report our experience with management of clinically
      symptomatic pelvic lymphoceles following robotic-assisted prostatectomy using
      laparoscopic marsupialization.

PMID- 22629011
TI  - Commentary.

PMID- 22629012
TI  - Inflammatory myofibroblastic tumor of the urinary bladder diagnosed by anaplastic
      lymphoma kinase immunostaining.
AB  - Inflammatory myofibroblastic tumor (IMFT) of the urinary bladder is an unusual
      spindle cell lesion that exhibits cytologic atypia, infiltrative growth, and
      mitotic activity mimicking malignant tumors, such as leiomyosarcoma,
      rhabdomyosarcoma, and sarcomatoid carcinoma. Recently, anaplastic lymphoma kinase
      (ALK) gene translocations or ALK protein expression in IMFT has been reported,
      especially in patients of children and young adults. This lesion has been
      described in numerous locations in addition to the urinary bladder. The detection
      of ALK protein and ALK gene rearrangements are useful in distinguishing IMFT from
      spindle cell malignancies in the urinary bladder.

PMID- 22629013
TI  - Intrascrotal solitary neurofibroma: A case report and review of the literature.
AB  - Solitary Neurofibroma of the scrotum is an extremely rare benign tumor,
      particularly when it is not associated with neurofibromatosis type I. To the best
      of our knowledge, less than 10 cases have been reported in the English
      literature. Herein, we report a 52-year-old man with the diagnosis of scrotal
      solitary neurofibroma.

PMID- 22629014
TI  - Primary isolated echinococcal cyst of the seminal vesicle: A rare case.
AB  - Hydatid disease of the organs other than liver and lung is extremely rare.
      Although hydatid disease is endemic in India, we report a rare case of hydatid
      cyst in a young male primarily involving the seminal vesicle and aim to highlight
      the management of such cases. A 23 year old male farmer diagnosed with primary
      isolated echinococcal cyst of the seminal vesicle has been presented. Thorough
      investigations with radiological methods such as ultrasonography (abdominal and
      trans-rectal), and magnetic resonance imaging were carried out to aid in the
      diagnosis. Surgical excision of the lesion was carried out with careful removal
      of the cyst to prevent any bursting and spillage, leaving the seminal vesicle
      preserved. The cystic lesion was subjected to histopathological examination.
      Histopathology confirmed the diagnosis of hydatid disease. Postoperative period
      was uncomplicated and patient was discharged on seventh postoperative day.
      Patient was put on albendazole (10 mg/kg/day) for three cycles of 21 days each
      with a gap of one week between each cycle. There was no evidence of recurrence or
      development of cysts elsewhere in the body during the 2 year follow-up. Hydatid
      cyst of seminal vesicle is rare and should be kept in differential diagnosis of a
      cystic lesion in pelvis especially in regions where hydatid disease is endemic.
      Proper surgical and medical management to avoid any recurrences, and a regular
      follow-up, are of utmost importance to detect any late complications such as
      local recurrence of the disease and development of hydatidosis at the primary
      sites.

PMID- 22629015
TI  - Fat poor angiomyolipoma with lymphadenopathy: Diagnostic dilemma.
AB  - A 24-year-old lady presented with left flank pain of 3 months duration. She had
      stigmata of tuberous sclerosis complex in the form of angiofibromas on face, ash
      leaf macules on back and right upper limb and shagreen patches over back.
      Computed tomography scan of the abdomen showed 6.5 cm * 5.0 cm * 4.4 cm lobulated
      intensely enhancing exophytic mass lesion in mid pole of left kidney with
      significant para-aortic lymphadenopathy with no evidence of fat in the mass. She
      underwent radical left nephrectomy with a provisional diagnosis of renal cell
      carcinoma. Histopathological examination showed multicenteric angiomyolipoma
      involving kidney and para-aortic lymph nodes. This case report underscores the
      need for further research to differentiate fat-poor angiomyolipoma and
      lymphadenopathy from renal cell carcinoma.

PMID- 22629016
TI  - Commentary.

PMID- 22629017
TI  - Fournier's gangrene developing secondary to infected hydrocele: A unique clinical
      scenario.
AB  - We report the first case of Fournier's gangrene (FG) developing secondary to an
      infected hydrocele worldwide. We present a case report with a brief overview of
      the literature relating to FG and its aetiology, diagnosis and management. A 70
      year-old male was referred by his General Practitioner with a 2 week history of
      worsening symptoms of scrotal discomfort and swelling. Following clinical
      examination, an initial diagnosis of an infected right-sided hydrocele was made
      and treatment, consisting of antibiotics, was initiated. Despite showing good
      clinical improvement, several days later, necrotic areas were observed over the
      right hemiscrotum with spreading cellulitis. A diagnosis of FG was made. The
      patient was started on triple-therapy antibiotics and taken to the operating room
      for urgent surgical debridement. Necrotic skin and subcutaneous tissue extending
      over the perineum and lower anterior abdomen was debrided down to healthy tissue.
      A further debridement took place 2 days later. The patient continued to improve
      and was eventually discharged under the care of Plastic Surgeons for
      reconstruction of the soft tissue defect. FG is a type of necrotising fasciitis
      predominantly affecting the male perineal, perianal, genital and anterior
      abdominal wall regions. It has a significant mortality rate, and the key to
      survival is early detection and treatment consisting of antibiotics and surgical
      debridement of the affected area. To the best of our knowledge, this is the first
      reported case of FG developing secondary to an existing hydrocele without any
      prior urological intervention. The case highlights the important clinical
      diagnostic and therapeutic interventions required to prevent complications
      associated with this, potentially fatal, condition.

PMID- 22629018
TI  - Urological concern and postcrisis Japanese nuclear accident.

PMID- 22629019
TI  - Preface to the Journal of Cardiovascular Disease Research, second issue 2012.

PMID- 22629020
TI  - Fatal thrombocytopenia associated with intracardiac mass.

PMID- 22629021
TI  - Genotype-phenotype analysis of three Chinese families with Jervell and Lange
      Nielsen syndrome.
AB  - BACKGROUND: Long QT syndrome (LQTS) is characterized by QT prolongation, syncope
      and sudden death. This study aims to explore the causes, clinical manifestations
      and therapeutic outcomes of Jervell and Lange-Nielsen syndrome (JLNS), a rare
      form of LQTS with congenital sensorineural deafness, in Chinese individuals.
      MATERIALS AND METHODS: Three JLNS kindreds from the Chinese National LQTS
      Registry were investigated. Mutational screening of KCNQ1 and KCNE1 genes was
      performed by polymerase chain reaction and direct DNA sequence analysis. LQTS
      phenotype and therapeutic outcomes were evaluated for all probands and family
      members. RESULTS: We identified 7 KCNQ1 mutations. c.1032_1117dup
      (p.Ser373TrpfsX10) and c.1319delT (p.Val440AlafsX26) were novel, causing JLNS in
      a 16-year-old boy with a QTc (QT interval corrected for heart rate) of 620 ms and
      recurrent syncope. c.605-2A>G and c.815G>A (p.Gly272Asp) caused JLNS in a 12-year
      old girl and her 5-year-old brother, showing QTc of 590 to 600 ms and recurrent
      syncope. The fourth JLNS case, a 46-year-old man carrying c.1032G>A
      (p.Ala344Alasp) and c.569G>A (p.Arg190Gln) and with QTc of 460 ms, has been
      syncope-free since age 30. His 16-year-old daughter carries novel missense
      mutation c.574C>T (p.Arg192Cys) and c.1032G>A(p.Ala344Alasp) and displayed a
      severe phenotype of Romano-Ward syndrome (RWS) characterized by a QTc of 530 ms
      and recurrent syncope with normal hearing. Both the father and daughter also
      carried c.253G>A (p.Asp85Asn; rs1805128), a rare single nucleotide polymorphism
      (SNP) on KCNE1. Bizarre T waves were seen in 3/4 JLNS patients. Symptoms were
      improved and T wave abnormalities became less abnormal after appropriate
      treatment. CONCLUSION: This study broadens the mutation and phenotype spectrums
      of JLNS. Compound heterozygous KCNQ1 mutations can result in both JLNS and severe
      forms of RWS in Chinese individuals.

PMID- 22629022
TI  - Wall shear stress and local plaque development in stenosed carotid arteries of
      hypercholesterolemic minipigs.
AB  - BACKGROUND: Wall shear stress is thought to play a critical role in the local
      development of atherosclerotic plaque and to affect plaque vulnerability.
      However, current models and hypotheses do not fully explain the link between wall
      shear stress and local plaque development. We aimed to investigate the relation
      between wall shear stress and local plaque development in surgically induced
      common carotid artery stenoses of hypercholesterolemic minipigs. MATERIALS,
      METHODS AND RESULTS: We created a surgically induced stenosis of the common
      carotid artery in 10 minipigs using a perivascular collar. We documented the flow
      and shear stress changes by ultrasound, magnetic resonance imaging, and
      computational fluid dynamics. Carotid plaques were documented by microscopy.
      Atherosclerotic lesions, in both pre-stenotic and post-stenotic segments, were
      associated with thrombus in the stenosed segment. In patent carotid arteries,
      atherosclerotic lesions were found in the post-stenotic segments only.
      Atherosclerotic lesions developed where low and oscillatory shear stress were
      present simultaneously, whereas low or oscillatory shear stress alone did not
      lead to lesion formation. CONCLUSIONS: Low and oscillatory shear stress in
      combination promoted plaque development, including plaques with necrotic cores
      that are the key and dangerous characteristic of vulnerable plaques.

PMID- 22629023
TI  - Tumor necrosis factor-alpha G-308 A polymorphism and risk of coronary heart
      disease and myocardial infarction: A case-control study and meta-analysis.
AB  - OBJECTIVES: The tumor necrosis factor-alpha (TNF-alpha) gene may play an
      important role in coronary heart disease (CHD) and myocardial infarction (MI)
      risk. Recently, controversial results regarding the association of the G-308 A
      (rs1800629)polymorphism of the TNF-alpha gene with CHD/MI have been reported. We
      herein examine a possible association between the G-308 A (rs1800629)polymorphism
      of the TNF-alpha gene and CHD/MI in a sample of the Chinese Han population.
      MATERIALS AND METHODS: We determined the genotypes of TNF-alpha G-308 A
      (rs1800629) in 535 unrelated Chinese patients with CHD, 420 patients with MI, and
      1020 coronary artery disease-free controls. Additionally, a meta-analysis of all
      previous studies on the TNF-alpha G-308 A polymorphism and the risk of CHD and MI
      was performed. RESULTS: AA genotypes in the G-308 A (rs1800629)polymorphism of
      the TNF-alpha gene did not occur more frequently in CHD/MI patients than in
      controls; odds ratios (95% confidence intervals) were 1.743 (0.325 to 1.423) for
      CHD and 1.731 (0.442 to 1.526) for MI, after adjusting for conventional risk
      factors. Further stratification for age, gender, and other cardiovascular risk
      factors did not alter the prior negative findings. Pooled meta-analysis of 23
      studies also found no statistically significant associations between the TNF
      alpha polymorphism and CHD/MI risk in the genetic additive, dominant, and
      recessive models. Subgroup analyses showed no association between the TNF-alpha
      polymorphism and CHD/MI in Asian and Caucasian populations. CONCLUSION: Our study
      showed no association between the G-308 A (rs1800629) polymorphism of the TNF
      alpha gene (presence of A allele) and CHD/MI in the Chinese Han population. There
      was no evidence of a difference in risk effects of rs1800629 between Caucasians
      and Asians.

PMID- 22629024
TI  - Risk factors of cardiovascular disease among children with chronic kidney disease
      in Gaza strip.
AB  - BACKGROUND: Chronic kidney disease (CKD) is increasingly recognized as a global
      public health problem. Cardiovascular disease (CVD) is a major cause of mortality
      in patients with mild-to-moderate CKD and end-stage renal disease. There is
      accumulating evidence that the increase in CVD burden is present in CKD patients
      prior to dialysis, due both to conventional risk factors and kidney-specific
      disease. Detection and initiation of treatment for CVD risk factors at early
      stages of CKD should be effective in reducing CVD events before as well as after
      the onset of kidney failure. MATERIALS AND METHODS: The study sample consisted of
      a total of 112 subjects aged <=12 years: 60 CKD patients and 52 healthy control
      individuals. All subjects were investigated for a group of CVD risk factors such
      as: Hypertension, diabetes, dyslipidemia, physical inactivity, body mass index
      (BMI), family history of CVD, hypoalbuminemia, albuminuria, anemia, Ca x P
      product, and inflammation in terms of C-reactive protein (CRP). RESULTS: Patients
      (40 males and 20 females) were categorized into four CKD stages (2, 3, 4, and 5)
      where, Stage 4 had the highest frequency, followed by Stages 3, 5 and 2.
      Evaluation of the patients indicated that they were shorter, had lower weight and
      had higher systolic and diastolic blood pressure as compared with control
      subjects. Frequency of physical inactivity among patients was two-fold higher
      than controls (50% vs. 25%). The patients showed significantly higher levels of
      cholesterol (163.6+/-39.8 vs. 141.8+/-24.2 mg/dL, P<0.0001), triglycerides
      (145.5+/-67.1 vs. 82.9+/-39.8 mg/dL, P<0.0001), low-density lipoprotein (92.6+/
      31.9 vs. 72.5+/-19 mg/dL, P<</i>0.0001) and albumin/creatinine ratio (1792+/-3183
      vs. 11.1+/-6.6 mg/g, P<0.0001). Moreover, the patients had lower levels of high
      density lipoprotein (41.9+/-11.0 vs. 52.7+/-11.7 mg/dL, P<0.0001), hemoglobin
      (9.8+/-1.4 vs. 11.9+/-0.8 g/dL, P<0.0001) and albumin (4.6+/-0.6 vs. 4.8+/-0.2
      g/dL, P=0.012). The CRP showed higher occurrence among patients (40% were
      positive for CRP). Calcium and phosphorus evaluation showed significantly lower
      calcium and higher phosphorus among patients. However, the difference in Ca X P
      product was not statistically significant. CONCLUSIONS: The study indicates that
      many of the CVD risk factors are associated with the different stages of CKD in
      children patients prior to dialysis, and that some of these factors are
      exacerbated as CKD progresses.

PMID- 22629025
TI  - Variability in cardiovascular functions and baroflex sensitivity following
      inhalation of petroleum hydrocarbons.
AB  - OBJECTIVE: Although petroleum products are useful chemical compounds which form
      an integral part of our modern technology, they have been reported to cause
      deleterious effect on health following their inhalation. Petroleum hydrocarbons
      dependent health hazards and their mechanisms have been associated with the
      routes of administration. This study, therefore, aimed at the isolation and
      chemical characterization of various petroleum products, and also investigating
      in rat model of Sprague dawley strain, the variability in cardiovascular
      functions and possible mechanism following inhalation of petroleum products.
      MATERIALS AND METHODS: Control rats were not exposed to any form of petroleum
      products, while the petrol-exposed, diesel-exposed, and kerosene-exposed were
      exposed to petrol, diesel, and kerosene respectively. RESULTS: When compared with
      the controls, all exposed groups showed a significant (P<0.05) increase in the
      systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP),
      and heart rate (HR). In comparison with the control, exposure to petroleum
      products also led to significant (P<0.05) increase in baroreflex sensitivity in
      the diesel- and kerosene-exposed rats. Baroreflex sensitivity was comparable in
      the control and petrol-exposed rats (P>0.05). Body weight gain was significantly
      (P<0.05) reduced in petroleum products exposed rats. CONCLUSION: These results
      suggest that the variability of cardiovascular functions associated with
      inhalation of petroleum products is in attendant to baroreflex sensitivity and
      resetting of arterial pressure.

PMID- 22629026
TI  - Family history of type 2 diabetes and prevalence of metabolic syndrome in adult
      Asian Indians.
AB  - BACKGROUND: Our objective was to test the association between familial risk of
      type 2 diabetes mellitus (T2DM) and the prevalence of metabolic syndrome (MS) in
      adult Asian Indians. MATERIALS AND METHODS: A total of 448 adult (>30 years)
      individuals (257 males and 191 females) participated in the study. Familial risk
      of T2DM was classified into three groups viz., 1=both parents affected; 2=parent
      and/or siblings affected and 3=none or no family history for T2DM. Anthropometric
      measures, blood pressures, fasting blood glucose and metabolic profiles were
      studied using standard techniques. MS was defined accordingly. The prevalence of
      MS phenotypes was estimated and compared among the three familial risk strata.
      RESULTS: Individuals with a history of both parents affected from diabetes had
      significantly higher (P<0.001) body mass index (BMI), waist circumference (WC),
      waist-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure
      (DBP) and fasting blood glucose (FBG; P=0.035) than individuals having no family
      history of T2DM. Significant difference was also noticed between individuals with
      and without MS according to the family history of diabetes (P<0.001). Differences
      were evident between individuals who fulfilled all the MS criteria (P=0.001) and
      individuals with only one or two criteria (phenotypes) according to family
      history of T2DM. CONCLUSION: Family history of T2DM had significant effect on
      individuals with MS as compared to their counterparts (individuals having no
      family history of T2DM). It therefore seems reasonable to argue that family
      history of T2DM could be useful as a predictive tool for early diagnosis and
      prevention of MS in Asian Indian population.

PMID- 22629027
TI  - Liver cirrhosis prevents atrial fibrillation: A reality or just an illusion?
AB  - OBJECTIVES: In cirrhotic patients, despite presence of significant metabolic
      abnormalities and enlarged left atria, we have seldom observed atrial
      fibrillation (AF) rhythm. The aim of this study was to evaluate the prevalence of
      AF among cirrhotic patients and comparing it with that reported in the general
      population. MATERIALS AND METHODS: Medical documents of 1302 adult cirrhotic
      patients, booked in the waiting list of liver transplantation, were evaluated
      retrospectively. Electrocardiograms were reviewed for the presence of AF rhythm,
      and echocardiographies were reviewed to obtain left atrial (LA) size. RESULT:
      Only two patients (0.15%) were detected to have AF rhythm, which was
      significantly lower than that reported in our general population, even after age
      and sex adjustment. Six hundred and sixty-eight patients (51%) had enlarged left
      atria (LA diameter more than 39mm); both AF patients belonged to this group.
      CONCLUSION: The result of this study suggests the protective effect of liver
      cirrhosis on development of atrial fibrillation. Further studies are needed to
      verify the possible mechanisms.

PMID- 22629028
TI  - High prevalence of cardiovascular diseases among other medically compromised
      conditions in dental patients: A retrospective study.
AB  - BACKGROUND: Over the last few decades, oral health care has become a greater
      priority as people live longer with serious medical conditions and disabilities.
      As a result, they require more comprehensive dental treatment. We are now, more
      than ever, at a turning point in history where dental care, or more broadly oral
      health care, is an integral part of medical care. Therefore, a need was felt to
      study the prevalence of medically compromised patients seeking dental treatments.
      MATERIALS AND METHODS: The present study was a retrospective study conducted by
      reviewing the patient records starting from 1(st) January 2009 to 31(st) December
      2010 for the presence of medically compromised conditions. Demographic data of
      the patients was also collected. RESULTS: The prevalence of medically compromised
      conditions in dental patients of our hospital in the present study was 1.02%. The
      Cardiovascular diseases accounted to be the most prevalent condition (57.87%)
      followed by Endocrine disorders (35.73%). CONCLUSION: Even though the prevalence
      of medically compromised conditions in dental patients is not high, dentists
      should bear in mind that some of the patients may harbor such conditions, which
      are contraindicated for certain dental procedures or medication or require
      special attention when treating these patients.

PMID- 22629029
TI  - The prevalence of hypertension and hypertension risk factors in a rural Indian
      community: A prospective door-to-door study.
AB  - BACKGROUND: The aim of this study was to identify the prevalence and risk factors
      for hypertension in a rural community in north-east India. MATERIALS AND METHODS:
      A door-to-door survey was conducted amongst all residents of a village in
      Uttarakhand province. All residents were interviewed and data were was relating
      to the demographics of the individuals, dietary habits, alcohol consumption,
      tobacco use, psychosocial stress, past medical history and drug history. Blood
      pressure (BP) and anthropometric data was recorded and blood samples taken.
      RESULTS: We identified 1348 people living in the village. Assessment was carried
      out on all those aged 15 years and over (n=968, 71.8%). Hypertension, defined as
      BP >= 140/90 mmHg or cases of known hypertensive on medication, were present in
      30.9% (95% CI 25.6 to 36.0) of males and 27.8% (95% CI 23.4 to 32.2) of females.
      Standardisation to the World Health Organization (WHO) world population gives an
      overall prevalence of 32.3% (95% confidence interval, CI 28.9 to 35.8).
      Increasing age and higher body mass index (BMI) were independent predictors of
      hypertension in both sexes, with psychosocial stress an additional independent
      predictor in males. CONCLUSIONS: Rates of hypertension in the rural community
      under study are similar to those seen in high-income countries and in urban
      India. With the exception of age, all the risk factors identified were
      potentially modifiable.

PMID- 22629030
TI  - Assessment of the effect of periodontal treatment in patients with coronary
      artery disease : A pilot survey.
AB  - BACKGROUND: Periodontitis is a chronic inflammatory condition believed to cause a
      low but long lasting systemic inflammatory reaction which in turn contributes to
      the development of atherosclerosis. Recent data suggests that around 40% cases of
      coronary artery disease remain unaccounted despite the identification of the
      classical risk factors. OBJECTIVES: To evaluate the efficacy of non surgical
      periodontal therapy on the levels of serum inflammatory markers in subjects with
      chronic periodontitis and known coronary artery disease. MATERIALS AND METHODS:
      Twenty subjects with known coronary artery disease (CAD) were recruited from the
      Department of Cardiology, CSM Medical University, Lucknow, India, for this study.
      Periodontal disease was measured through the clinical parameters bleeding on
      probing (BOP) and probing depth (PD). All subjects received non surgical
      periodontal therapy that included oral hygiene instructions and meticulous
      scaling and root planing. Systemic levels of inflammatory markers such as high
      sensitivity C reactive proteins (hsCRP), tumor necrosis factor-alpha (TNF-alpha),
      and white blood cell (WBC) counts were measured prior to and 1 month after
      periodontal therapy. RESULTS: Subjects experienced significant reductions in
      bleeding on probing (BOP) and probing depth (PD), indicating improvement in
      overall periodontal health. In all subjects, high-sensitivity C reactive proteins
      (hsCRP), and WBC counts were reduced significantly,; however, tumor necrosis
      factor-alpha (TNF-alpha) levels showed no statistically significant reduction.
      CONCLUSION: In this study, periodontal treatment resulted in a significant
      decrease in bleeding on probing (BOP) and probing depth (PD), and this treatment
      lowered the serum inflammatory markers (hsCRP and WBC counts) in patients with
      coronary artery disease. This may result in a decreased risk for coronary artery
      disease in the periodontally treated patients.

PMID- 22629031
TI  - Measurement of intima media thickness of carotid artery by B-mode ultrasound in
      healthy people of India and Bangladesh, and relation of age and sex with carotid
      artery intima media thickness: An observational study.
AB  - BACKGROUND: Carotid artery intima media is a surrogate marker of atherosclerosis
      and related with ethnicity, age, sex, traditional and non-traditional risk
      factors. Black ethnicity is related to greater mean and maximum carotid artery
      intima media thickness when compared to South Asians. Our study was done to find
      out the mean carotid artery intima media thickness (CAIMT) of normal healthy
      people of India and Bangladesh, and the relationship of non-modifiable risk
      factors such as age and sex with CAIMT. MATERIALS AND METHODS: In this
      observational study, CAIMT of 93 people were examined by B-mode ultrasonography.
      All subjects underwent a careful interview and clinical, radiological,
      biochemical examination. Data was analyzed by software statistical package for
      social sciences (SPSS) (17(th) version for window). RESULTS: In our study, the
      mean CAIMT of healthy subjects including all age group was (754.94 +/- 11.96
      micron.). Mean CAIMT was higher in age group of 61-80 years (908.75 +/- 39.02
      micron) than age group of 20-40 years (713.62 +/- 16.59 micron) and 41-60 years
      (745.55 +/- 13.05 micron). CAIMT was positively correlated with age (P value
      <0.001) and sex (P value=0.001). CONCLUSION: An aggregated analysis based on this
      study in different age groups of healthy people may be useful for assessing
      carotid artery abnormalities as an aid to defining abnormalities and predicting
      risk of atherosclerosis in individual healthy people living in India and
      Bangladesh.

PMID- 22629032
TI  - Ruptured right sinus of Valsalva into main pulmonary artery.
AB  - A young adult who presented with congestive heart failure was found to have
      ruptured aneurysm of right sinus of Valsalva. The aneurysm was opening into the
      main pulmonary artery, which was demonstrated well by transthoracic and
      transesophageal echocardiography and confirmed by cardiac catheterization.
      Aneurysm was repaired followed by aortic valve replacement.

PMID- 22629033
TI  - Acute superior vena cava obstruction due to tight pericardial closure following
      congenital defect repair.
AB  - The obstruction of the superior vena cava (SVC) of acute onset nature following
      surgery is a rare and serious condition. The tight closure of the pericardium
      over the heart during surgical procedures may cause external compression on the
      SVC. Echocardiography and Computed tomography (CT) scan aids in the diagnosis.
      Cutting open the pericardial stitches relieves the condition.

PMID- 22629034
TI  - Inferior myocardial infarction secondary to aortic dissection associated with
      bicuspid aortic valve.
AB  - Aortic dissection (AD) is a life-threatening condition and may present with
      symptoms which mimic myocardial infarction, leading to misdiagnosis and
      inappropriate use of anticoagulant and thrombolytic therapy. A 40-year-old woman
      with no prior history presented in our emergency department with sudden chest
      pain. Electrocardiography (ECG) showed a ST-segment elevation in leads II, III
      and avF, suggesting an acute inferior myocardial infarction. The patient was
      given anticoagulation and antiplatelet treatment. Coronary angiography,
      transthoracic echocardiography and computed tomography were performed. The
      patient was diagnosed with DeBakey I aortic dissection extending from ascending
      aorta to iliac artery, and associated with bicuspid aortic valve.Surgical
      treatments with a replacement of the ascending aorta, aortic valve replacement
      and coronary artery bypass grafting were successfully performed. Early imaging
      examination, if possible, might assist the diagnosis and guide the management of
      this disease. The condition of myocardial infarction secondary to aortic
      dissection is discussed.

PMID- 22629035
TI  - A tetrad of bicuspid aortic valve association: A single-stage repair.
AB  - We report a 27 years old male who presented with a combination of both congenital
      and acquired cardiac defects. This syndrome complex includes congenital bicuspid
      aortic valve, Seller's grade II aortic regurgitation, juxta- subclavian
      coarctation, stenosis of ostium of left subclavian artery and ruptured sinus of
      Valsalva aneurysm without any evidence of infective endocarditis. This type of
      constellation is extremely rare. Neither coarctation of aorta with left
      subclavian artery stenosis nor the rupture of sinus Valsalva had a favorable
      pathology for percutaneus intervention. Taking account into morbidity associated
      with repeated surgery and anesthesia patient underwent a single stage surgical
      repair of both the defects by two surgical incisions. The approaches include
      median sternotomy for rupture of sinus of Valsalva and lateral thoracotomy for
      coarctation with left subclavian artery stenosis. The surgery was uneventful.
      After three months follow up echocardiography showed mild residual gradient
      across the repaired coarctation segment, mild aortic regurgitation and no
      residual left to right shunt. This patient is under follow up. This is an
      extremely rare case of single stage successful repair of coarctation and rupture
      of sinus of Valsalva associated with congenital bicuspid aortic valve.

PMID- 22629036
TI  - Fatal thrombocytopenia: A rare case with possible explanation.
AB  - A 22 year old male presented with breathlessness on exertion, ecchymosis,
      jaundice and features of worsening right heart failure for the last fifteen days.
      On physical examination, he had a mid diastolic murmur in the tricuspid area and
      an ejection systolic murmur in the pulmonary area. Bone marrow histopathology
      report showed an increased in megakaryocytes count. Routine investigations
      reports were normal. Echocardiography and computerized tomography (CT) revealed a
      single mobile large intra cardiac mass originating from the right atrium and
      causing dynamic obstruction of the right ventricular inflow and outflow tract.
      Associated fatal thrombocytopenia did not respond to intravenous steroids or
      platelet transfusion. Patient could not be operated because of very low platelet
      count, and died during hospital stay before excision biopsy could be done.
      Pathological autopsy was not done. This is a rare case, as the fatal
      thrombocytopenia observed here was the result of mechanical effects like
      frictional and shear force, which can be attributed to the physical presence of a
      large intra cardiac mass resulting in obstruction to flow.

PMID- 22629037
TI  - Molecular diagnosis of generalized arterial calcification of infancy (GACI).
AB  - Generalized arterial calcification of infancy (GACI) is a life-threatening
      disorder in young infants. Cardiovascular symptoms are usually apparent within
      the first month of life. The symptoms are caused by calcification of large and
      medium-sized arteries, including the aorta, coronary arteries, and renal
      arteries. Most of the patients die by 6 months of age because of heart failure.
      Recently, homozygous or compound heterozygous mutations for the ectonucleotide
      pyrophosphatase/phosphodiesterase 1 (ENPP1) gene were reported as causative for
      the disorder. ENPP1 regulates extracellular inorganic pyrophosphate (PP(i)), a
      major inhibitor of extracellular matrix calcification. A newborn was diagnosed
      with GACI. The infant died at the age of 7 weeks of cardiac failure and the
      parents were referred to Molecular Biology and Cytogenetic lab for further
      workup. Cytogenetics analysis was performed on the parents, which showed normal
      karyotypes and mutational analysis for the ectonucleotide
      pyrophosphatase/phosphodiesterase 1 (ENPP1) gene was also performed. The
      mutational analysis showed that both father and mother of the deceased infant
      were heterozygous carriers of the mutation c.749C>T (p.P250L) in exon 7 of ENPP1
      and it was likely, that the deceased child carried the same mutation homozygous
      on both alleles and died of GACI resulting from this ENPP1 mutation. The couple
      was counseled and monitored for the second pregnancy. Amniocentesis was performed
      at 15 weeks of gestation for mutational analysis of the same gene in the second
      pregnancy. The analysis was negative for the parental mutations. One month after
      the birth of a healthy infant, peripheral blood was collected from the baby and
      sent for reconfirmation. The results again were negative for the mutation and the
      baby was on 6 months follow up and no major symptoms were seen. The parents of
      the child benefited enormously by learning about the disease much in advance and
      also its risk of recurrence. The main aim of this study is to emphasize on two
      aspects: (i) the importance of modern molecular techniques in diagnosis such a
      syndrome and (2) the difficulties faced by the physician to provide appropriate
      diagnosis and the adequate genetic counseling to the family without molecular
      facilities.

PMID- 22629038
TI  - Device closure of post-myocardial infarction ventricular septal defect three
      weeks after coronary angioplasty.
AB  - Percutaneus device closure appears to be safe and effective in patients treated
      for a residual shunt after initial surgical closure, as well as after two to
      three weeks of index myocardial infarction. The index case presented with a
      ventricular septal defect on second of acute myocardial infarction thrombolysed
      with streptokinase. The general condition of the patient was fairly stable.
      Cardiac catheterization and coronary angiography showed significant left to right
      shunt and there was 90 % proximal stenosis of left anterior descending coronary
      artery. Other coronary arteries were normal. Angioplasty and stenting to the
      coronary artery lesion was done using drug eluting stent (DES) with very good
      angiographic result. Patient was discharged after four days in stable condtion.
      After 3 weeks his ventricular septal defect was closed percutaneusly using cardio
      -O-fix device with tiny residual shunt. The procedure was uneventful and of brief
      duration. He was discharged after 5 days of the post procedure in very stable
      condition with minimal residual shunt. A staged procedure is a better option if
      the condition of the patient allows strengthening ventricular septal defect
      border.

PMID- 22629039
TI  - Pheochromocytoma with inferior vena cava thrombosis: An unusual association.
AB  - Pheochromocytomas have been described in association with vascular abnormalities
      like renal artery stenosis. A 48-year-old man was admitted to our hospital with
      the complaints of headache, sweating, anxiety, dizziness, nausea, vomiting and
      hypertension. For last several days, he was having a dull aching abdominal pain.
      Abdominal computed tomography (CT) revealed the presence of a left adrenal
      pheochromocytoma. An inferior vena cava (IVC) venogram via the right jugular vein
      demonstrated occlusion of the IVC inferior to the right atrium. Surgical removal
      of pheochromocytoma was done, followed by anticoagulant treatment for IVC
      thrombosis, initially with subcutaneous low molecular weight heparin, and then
      with oral warfarin, resulting in restoration of patency. To the best of our
      knowledge, the occurrence of pheochromocytoma in IVC thrombosis has not been
      reported so far from India. Possible mechanisms of such an involvement are
      discussed.

PMID- 22629040
TI  - Chest pain with ST-T changes on electrocardiogram and localized stenosis on
      coronary angiography could be a coronary vasospasm.
AB  - Coronary vasospasm is characterized by chest pain at rest with ST-T changes on
      electro cardiogram and coronary angiography showing virtually normal coronaries.
      The definitive diagnosis requires the stimulation of coronary vasospasm using
      provocative agents, which can be life threatening. We present a case where
      localized stenosis of proximal left anterior descending artery was observed on
      the coronary angiography, which disappeared on subsequent views, and hence,
      coronary stenting was deferred and patient responded well to medical management
      alone.

PMID- 22629042
TI  - Coexistence of Cor triatriatum sinistrum and a prominent Eustachian valve
      mimicking a Cor triatriatum dextrum.
AB  - Cor triatriatum is among the rarest of all congenital cardiac abnormalities
      accounting for 0.1-0.4% of all congenital heart disease. Its coexistence with a
      very prominent Eustachian valve which mimics a Cor triatriatum dextrum is an
      exceptionally rare finding in an asymptomatic adult. We report the case of a 44
      year old male who presented to our department on observing a pulse rate of 44
      beats per minute during a home blood pressure check with his digital
      sphygmomanometer. Clinical examinationwas however, unremarkable and resting
      electrocardiography showed sinus rhythm with atrial premature complexes. The
      diagnosis was made on a two dimensional transthoracic echocardiography. Isolated
      atrial premature complexes and bradycardia may be a clinical presentation of Cor
      triatriatum in adult population. Although extremely rare, its coexistence with a
      prominent Eustachian valve may remain asymptomatic into adult life.

PMID- 22629041
TI  - ST segment elevation myocardial infarction as a presenting feature of thrombotic
      thrombocytopenic purpura.
AB  - Myocardial infarction with ST segment elevation (STE) on electrocardiography
      (ECG) is a common presentation in emergency rooms across the world. Myocardial
      injury and necrosis are infrequently the initial presentation in patients with
      thrombotic thrombocytopenic purpura (TTP). A 48-year-old woman presented with STE
      myocardial infarction from outside hospital for primary percutaneous coronary
      intervention. However, her clinical picture was not consistent. Rapid evaluation
      revealed symptoms associated with microangiopathic hemolytic anemia,
      thrombocytopenia, acute kidney injury with waxing and waning mental status. A
      diagnosis of TTP was made with low ADAMST-13 activity. Plasmapheresis was
      initiated along with intravenous steroid therapy. The patient had a full recovery
      and went home after full recovery of left ventricular ejection fraction and
      normal myocardial perfusion studies. Rapid evaluation is needed to identify
      infrequent causes of STE myocardial infarction. As swift protocols are activated
      in the emergency room and catheterization laboratories to ensure quality control,
      it is equally important to integrate all aspects of the patient's clinical and
      objective data to detect unusual disease entities.

PMID- 22629043
TI  - Cardiorenal syndrome: Resistant to diuretics, sensitive to ultraflitration.
AB  - Cardiac and renal diseases are becoming increasingly common today, and are seen
      to frequently coexist, thus causing a significant increase in the mortality rate,
      morbidity, complexity of treatment and cost of care. Syndromes describing the
      interaction between heart and kidney have been defined and classified; however,
      never as a result of a consensus process. Though the incidence of cardiorenal
      syndrome is increasing, the associated pathophysiology and effective management
      are still not well understood. For many years, diuretics and ultrafiltration,
      have been the mainstay of treatment for cardiorenal syndrome, although a
      significant proportion of patients develop resistance to diuretics, and even
      deteriorate while on diuretics. Here, we will discuss one such patient who failed
      to respond to the optimum doses of diuretics; however, his blood urea and serum
      creatinine touched the baseline levels post-ultrafiltration.

PMID- 22629044
TI  - Atherosclerosis and myocardial bridging: Not a benign combination. An autopsy
      case report.
AB  - Myocardial bridging is a congenital coronary anomaly with a variety of clinical
      manifestations. Traditionally, myocardial bridging has been considered a benign
      condition, but some cases of myocardial ischemia, infarction and sudden cardiac
      death due to myocardial bridging have been reported. Various studies have
      suggested that in their intramyocardial segments, these vessels are protected
      from obstructive atherosclerosis, with atherosclerosis being present in the
      proximal part of the artery. We report a case in a 45-year-old male who had a 2.5
      cm long myocardial bridging over the left anterior descending artery, with
      obstructive atherosclerosis being present in the proximal as well as the
      intramyocardial part (part of the artery below the myocardial bridge).
      Atherosclerosis occurring in the intramyocardial segment is a rare occurrence,
      and combined with systolic narrowing by the myocardial bridge can lead to
      ischemia of the cardiac musculature.

PMID- 22629045
TI  - Lutembacher's syndrome.
AB  - The definition of Lutembacher's syndrome has undergone many changes. It refers to
      combination of congenital Atrial Septal Defect with acquired mitral stenosis.
      Lutembacher's syndrome is a very rare disease and in the past, it has been either
      overdiagnosed or misdiagnosed. Here, we will discuss a case of a pregnant lady
      who developed breathlessness during her third trimester of pregnancy and on
      detailed examination and investigation, she was found to be having Lutembacher's
      syndrome.

PMID- 22629046
TI  - Sweet but toxic poison?

PMID- 22629047
TI  - Recurrent bimaxillary radiopacities: A rare case report.
AB  - Cemento-ossifying fibroma (COF) is considered a benign osseous tumor. Herewith,
      we present a case of multiple central ossifying fibroma in a 35-yeaold woman.
      Intraorally, there was swelling in the left upper posterior teeth region and
      another diffused swelling in the fourth quadrant. Radiographs revealed the
      presence of well-defined mixed radiolucent-radiopaque area having thin
      radiolucent rim followed by thick sclerotic margin. No genetic correlation could
      be established. As bilateral COF is a rare entity, we present such a case with
      different radiographic appearance, using various radiographic techniques.

PMID- 22629048
TI  - Traumatic ulcerative granuloma with stromal eosinophilia of the palate showing an
      angiocentric/angiodestructive growth pattern.
AB  - Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a benign,
      self-limiting lesion of the oral mucosa with unknown pathogenesis. A 65-year-old
      male patient presented with an ulcerative palate lesion, which on microscopic
      examination exhibited an exuberant polymorphic lymphoid proliferation, numerous
      eosinophils, and extensive vascular destruction. The atypical lymphoid cells
      infiltrating the medium-sized vessels showed positivity for CD3, CD30, and
      granzyme B, implicating an activated cytotoxic T-cell phenotype. The lesion
      diagnosed as TUGSE achieved complete resolution within 3 months. This unusual
      presentation has expanded the spectrum of oral CD30+ T-cell atypical infiltrates
      and must be distinguished from lymphomas showing angiocentric/angiodestructive
      growth pattern.

PMID- 22629049
TI  - Fibrolipoma of buccal mucosa.
AB  - The lipoma is a very common benign tumor of adipose tissue, but its presence in
      the oral and oropharyngeal region is relatively uncommon. Fibrolipoma, a
      histological variant of lipoma, mostly affect the buccal mucosa and causes
      functional and cosmetic disabilities. Hence, accurate histopathological
      examination of lipomas is important for a correct treatment plan. This article
      describes a case of 10 year old girl with fibrolipoma of the buccal mucosa with a
      relevant review of tumors.

PMID- 22629050
TI  - Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome: A case report
      of "Incomplete syndrome".
AB  - Ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) is a rare syndrome
      having ectrodactyly, ectodermal dysplasia, and cleft lip/palate. So far, very few
      cases have been reported in literature. However, we report a case of incomplete
      EEC syndrome having ectrodactyly and cleft lip and palate with absence of signs
      of ectodermal dysplasia with no other systemic anomalies. Other feature noted is
      the syndactyly of toes which is reported rarely in this syndrome. A
      multidisciplinary approach for treatment is needed which is co-ordinated by
      pedodontist or pediatrician.

PMID- 22629051
TI  - Peripheral giant cell granuloma.
AB  - Peripheral giant cell granuloma or the so-called "giant cell epulis" is the most
      common oral giant cell lesion. It normally presents as a soft tissue purplish-red
      nodule consisting of multinucleated giant cells in a background of mononuclear
      stromal cells and extravasated red blood cells. This lesion probably does not
      represent a true neoplasm, but rather may be reactive in nature, believed to be
      stimulated by local irritation or trauma, but the cause is not certainly known.
      This article reports a case of peripheral giant cell granuloma arising at the
      maxillary anterior region in a 22-year-old female patient. The lesion was
      completely excised to the periosteum level and there is no residual or recurrent
      swelling or bony defect apparent in the area of biopsy after a follow-up period
      of 6 months.

PMID- 22629052
TI  - Adolescent rampant caries.
AB  - Adolescent rampant caries is a new and growing challenge in Conservative
      Dentistry. It has the same etiology and pattern as that of nursing bottle
      syndrome. Herein, a case is presented in which the main cause of rampant caries
      is the patient's habit of keeping cariogenic food in her mouth and going to
      sleep. Educating this etiology and introduction of preventive strategies not only
      assists in meeting the special oral needs of the adolescent population, but also
      helps to establish lifelong healthful habits.

PMID- 22629053
TI  - Facial talon cusp: A rarity, report of a case with one year follow up and
      flashback on reported cases.
AB  - Talon cusp is a relatively uncommon developmental anomaly characterized by cusp
      like projections, usually presenting on palatal/lingual surface of the anterior
      teeth. This cusp resembles an eagle's talon, and hence the name. Normal enamel
      and dentin covers the cusp, which may or may not contain an extension of pulp.
      Presence of this anomalous cusp on the facial surface of an anterior tooth is a
      rare finding and very few cases have been reported in the literature. In most
      instances, such cusps are associated with clinical problems such as poor
      esthetics and caries susceptibility. Management of such cases requires a
      comprehensive knowledge of the clinical entity as well as the problems associated
      with it. This case report presents a facial talon cusp on the maxillary left
      central incisor of a 10 year old boy, which was conservatively treated. Vitality
      of the affected tooth was maintained and followed up for a period of 1 year.

PMID- 22629054
TI  - Compound odontoma.
AB  - Odontomas have been extensively reported in the dental literature, and the term
      refers to tumors of odontogenic origin. Though the exact etiology is still
      unknown, the postulated causes include: local trauma, infection, inheritance and
      genetic mutation. The majority of the lesions are asymptomatic; however, may be
      accompanied with pain and swelling as secondary complaints in some cases. Here,
      we report a case of a compound odontome in a 14 year old patient.

PMID- 22629055
TI  - Endodontic management of permanent mandibular left first molar with six root
      canals.
AB  - The endodontic treatment of a mandibular molar with aberrant canal configuration
      can be diagnostically and clinically challenging. This case report presents the
      treatment of a mandibular first molar with six root canals, of which three canals
      were located in the mesial root and three in distal root. Third canals were found
      between the two main root canals. This case presents a rare anatomic
      configuration and points to the importance of expecting and searching for
      additional canals.

PMID- 22629056
TI  - Three-rooted mandibular first primary molar: Report of three cases.
AB  - Accessory root formation in primary teeth is an uncommon finding. An awareness
      and understanding of the presence of additional roots and unusual root canal
      morphology is essential as it determines the successful outcome of the endodontic
      treatment.This paper presents three case reports on the presence of three-rooted
      mandibular first primary molar (primary three-rooted mandibular left first molar
      and bilateral mandibular first molar).

PMID- 22629057
TI  - Nodular fasciitis of the oro-facial region.
AB  - Nodular fasciitis is a benign proliferative spindle-cell lesion that presents as
      a rapidly growing mass frequently being mistaken for a sarcoma. A rare
      presentation and treatment of nodular fasciitis in the cheek of an 8-year-old boy
      is described here. He came with a chief complaint of swelling in the left cheek
      since 1 month which rapidly increased to the size of a marble, over a period of 1
      month. Surgical excision of the lesion was planned under general anesthesia
      following which the surgical site was closed with resorbable sutures. Based on
      the history, clinical picture, and histopathological examination, the lesion was
      diagnosed as nodular fasciitis. Although infrequent in both children and the oral
      mucosa, nodular fasciitis should be considered in the differential diagnosis of
      facial tumors in infants and young children.

PMID- 22629058
TI  - Oral myiasis in children.
AB  - Oral myiasis is a rare condition in humans and is associated with poor oral
      hygiene, severe halitosis, mouth breathing during sleep, mental handicap,
      cerebral palsy, epilepsy, anterior open bite, incompetent lips, and other
      conditions. In this report, a 14 year-old boy who had an orofacial trauma in the
      maxillary dentoalveolar region,which was neglected, has been described. There was
      a deep lacerated wound on the upper vestibule which was infected and maggots were
      found on the same wound. The clinical features, management, treatment are
      discussed and relevant literature is reviewed.

PMID- 22629059
TI  - Assessment of psychological effects of dental treatment on children.
AB  - AIM: The aim of present study is to investigate the various psychological effects
      on children due to dental treatment. MATERIALS AND METHODS: One hundred and
      eighty school going children, age range between six and twelve years, were
      recruited into the study and divided into two groups (Group I included six to
      nine-year-olds and Group II included nine-to-twelve year olds). Only those
      children were included who underwent a certain dental treatment seven days prior
      to the investigation. Each child was asked a preformed set of questions. The
      child was allowed to explain and answer in his own way, rather than only in yes
      or no. The answers were recorded. After interviewing, the child was asked either
      to draw a picture or to write an essay related to his experience regarding the
      dentist and dental treatment. RESULTS: A majority of the children (92.22%) had a
      positive perception. The number of children having negative and neutral
      perceptions was comparatively much less. Younger children (Group I) had a more
      negative experience than the older children (Group II). Only one-fourth of the
      children complained of some pretreatment fear (23.83%); 72.09% of the children
      did not have any pain during dental treatment and a majority of children (80.23%)
      remembered their dental treatment. CONCLUSION: A majority of children had a
      positive perception of their dental treatment and the children in the younger age
      group had more negative perceptions than the children in the older age group.

PMID- 22629060
TI  - Peripheral cemento-ossifying fibroma: Report of a recurrence case.
AB  - Peripheral cemento-ossifying fibroma [PCOF] is a reactive gingival overgrowth
      occurring frequently in the maxillary anterior region in teenagers and young
      adults. Here, we report a case of POCF in a 13-year-old male, which was
      previously surgically excised and had recurred after a period of 9 months. PCOF
      should be considered in differential diagnosis of such reactive hyperplastic
      lesions originating from the gingiva. Hence, early diagnosis with proper surgical
      excision and aggressive curettage of the adjacent tissues are essential for
      prevention of recurrence.

PMID- 22629061
TI  - Fiber reinforced composite loop space maintainer: An alternative to the
      conventional band and loop.
AB  - The stainless steel band and loop appliance is the most commonly used fixed space
      maintainer in pediatric dentistry. But there are several disadvantages with this
      appliance such as the need for a cast or a working model, decalcification of the
      abutment tooth, loosening because of breakage or dissolution of the luting agent,
      tendency to get embedded in the soft tissue and the possibility of metal allergy.
      The purpose of this article is to present a simple, laboratory design of a "Fiber
      Reinforced Composite" (FRC) loop space maintainer and discuss the advantages over
      the traditional band and loop space maintainers.

PMID- 22629062
TI  - Adenomatoid odontogenic tumor: As an unusual mandibular manifestation.
AB  - Adenomatoid odontogenic tumor (AOT) is a rare odontogenic tumor which is often
      misdiagnosed as odontogenic cyst and accounts for about 1% until 9% of all
      odontogenic tumors. It is predominantly found in young and female patients,
      located more often in the maxilla in most cases associated with an unerupted
      permanent tooth. It is a benign (hamartomatous), noninvasive lesion with slow but
      progressive growth. There are three variants of AOT: follicular, extrafollicular,
      and peripheral. We report a rare case of follicular-type AOT in the mandible of a
      14-year-old male patient who presented with right -sided jaw swelling.

PMID- 22629063
TI  - Oral rehabilitation of a young patient with hypohidrotic ectodermal dysplasia: A
      clinical report.
AB  - Ectodermal dysplasia (ED) represents a group of patients with mild to severe
      congenital and developmental anomalies. Dentists are the first person to identify
      ED in young patients. The impairment is not just the form and function but
      extends to the social outlook as well as the psychology of the affected
      individual. This case report describes management of ED with a long-span fixed
      partial denture fabricated using a Broadrick flag.

PMID- 22629064
TI  - Management of impacted dilacerated maxillary central incisor: A clinical case
      report.
AB  - The impacted maxillary incisor is detrimental for problems related to esthetics
      and occlusion in permanent dentition stage. A case with an unerupted maxillary
      central incisor was diagnosed radiographically with impacted dilacerated
      maxillary central incisor. The management of the case was carried out surgically
      and orthodontically. By combining two stages of surgical exposure, orthodontic
      traction and alignment, the impacted dilacerated incisor was successfully moved
      into desired position. A two-year follow-up of the stability and periodontal
      health showed that the tooth placed in the occlusion maintained both esthetics
      and function.

PMID- 22629065
TI  - Dentofacial characteristics in William's syndrome.
AB  - William's syndrome is a chromosomal disorder characterized by multisystem,
      congenital and panethnic occurrence, characterized by a number of developmental
      and physical abnormalities. This case report describes the dental management of a
      10-year-old male patient with William's syndrome who had multiple dental problems
      such as caries, periodontal disease and malocclusion.

PMID- 22629066
TI  - Trabeculae type of juvenile aggressive ossifying fibroma of the maxilla: Report
      of two cases.
AB  - Juvenile ossifying fibroma (JOF) is a rare controversial fibroosseous lesion
      affecting the craniofacial skeleton and occurring commonly in children and young
      adults. It is highly aggressive and has a high tendency to recur. It is
      distinguished from the adult variant of ossifying fibroma on the basis of age,
      site, clinical behavior and microscopic appearance. Because of its high
      recurrence rate, which is 30-58%, complete excision is essential. Early diagnosis
      will circumvent the necessity of radical treatment. We report a rare case of
      trabecular JOF of maxilla where a computed tomography scan was taken to further
      support the characteristic feature of the lesion.

PMID- 22629067
TI  - 3-D diagnosis-assisted management of anomalous mandibular molar.
AB  - This case report describes the successful non-surgical endodontic management of
      carious exposed three-rooted mandibular molar with four root canals detected on
      the pre-operative radiograph taken with 20 degrees mesial angulation and
      confirmed with a 64-slice helical computed tomography scan-assisted 3-D
      reconstructed images. Access cavity shape was modified to locate the extra canal
      with respect to the distolingual root in the left mandibular first molar. Copious
      irrigation was accomplished with 5.25% sodium hypochlorite and 17% EDTA.
      Biomechanical preparation was done using protapers. Calcium hydroxide dressing
      was done for 1 week. The tooth was obturated using gutta percha and AH 26 root
      canal sealer, and it was permanently restored with composite. Clinical
      examination on follow-up visits revealed no sensitivity to percussion and
      palpation in the left mandibular first molar. Thorough knowledge of root canal
      variations and use of advanced diagnostic modalities lead to successful non
      surgical management of the complex cases.

PMID- 22629068
TI  - Oral manifestations of Ellis-van Creveld syndrome.
AB  - Ellis-van Creveld syndrome is a rare autosomal-recessive disorder characterized
      by short limbs, post-axial polydactyly, ectodermal dysplasia, edentulous
      mandibular incisor region, absence of mucobuccal fold, congenitally missing
      teeth, slight serrations of the alveolar ridge and multiple small alveolar
      notches. The clinical report not only describes the classical oral and dental
      manifestations of Ellis-van Creveld syndrome but also presents unusual findings
      such as single-rooted and funnel-shaped primary first molars, single conical
      roots of primary second molars and taurodontisum, which must be considered in the
      differential diagnostic criteria to avoid misdiagnosis of syndromes. The article
      also discusses the differential diagnosis and preventive and therapeutic oral
      health care for these patients. The management of Ellis-van Creveld syndrome is
      multidisciplinary and, therefore, the oral health care provider should get
      updated with latest knowledge for timely referral to prevent the patient from
      further complications of heart defect and bony deformity.

PMID- 22629069
TI  - Focal cemento-osseous dysplasia masquerading as a residual cyst.
AB  - Focal cemento-osseous dysplasia (FCOD) is a benign fibroosseous condition that
      can be seen in dentulous and edentulous patients. It is an asymptomatic lesion
      and needs no treatment; however, follow-up is essential due to the possibility
      that it can progress to a condition called florid cemento-osseous dysplasia. We
      report a case of FCOD of mandible in a 25-year-old female. Clinically, the lesion
      resembled periapical pathosis of odontogenic origin. An attempt has been made to
      discuss the clinical and histopathologic features along with differential
      diagnosis of cemento-osseous dysplasia.

PMID- 22629070
TI  - Familial gingival fibromatosis: A rare case report.
AB  - Hereditary gingival fibromatosis is a rare condition that can occur as an
      isolated disease or as part of a syndrome or chromosomal abnormality. In severe
      cases, the gingival enlargement may cover the crowns of teeth and cause severe
      functional and aesthetic concerns. Here, we present a case of an 8-year-old girl
      with severe enlargement of gums in maxilla and mandible. Both deciduous and
      permanent teeth were not erupted in the oral cavity at all. Mutation in the Son
      of-Sevenless (SOS-1) gene has been associated with the disease. The diagnosis was
      made based on clinical examination and family history. Surgical removal of the
      hyperplastic tissue was performed under general anesthesia.

PMID- 22629071
TI  - A conservative approach toward restoration of fractured anterior tooth.
AB  - Reattachment of the fractured anterior tooth is a highly conservative and
      aesthetic treatment that has gained popularity in the recent past. Presented here
      is one such case in which a combination of external enamel bevel and internal
      dentinal groove has been used to enhance the bonding between the fractured
      fragment and the remaining tooth. The treatment was found to be successful both
      functionally and aesthetically at the 18-month follow-up.

PMID- 22629072
TI  - Supernumerary teeth: Report of four unusual cases.
AB  - Supernumerary tooth denotes duplication of tooth in the normal series. It is a
      developmental anomaly and has been argued to arise from multiple etiologies.
      These teeth may remain embedded in the alveolar bone or can erupt into the oral
      cavity. The supernumerary tooth might cause esthetic and/or functional problems,
      especially if it is situated in the maxillary anterior region. Complications
      reported were delayed or prevented eruption of succedaneous teeth, displacement
      or rotation, crowding of the affected region, abnormal diastema, dilacerations,
      cystic formation, and sometime eruption into the nasal cavity. In this case
      report, four unusual cases of supernumerary teeth that resulted in varying
      degrees of disturbances in permanent dentition are presented. Conservative
      surgical intervention and light orthodontic forces were used to bring the teeth
      into normal position with minimal disturbance to the surrounding oral structures.

PMID- 22629073
TI  - Progressive hemifacial atrophy (Parry-Romberg Syndrome).
AB  - Progressive hemifacial atrophy, also known as Parry-Romberg Syndrome, is an
      uncommon degenerative and poorly understood condition. It is characterized by a
      slow and progressive atrophy affecting one side of the face. The incidence and
      the cause of this alteration are unknown. A cerebral disturbance of fat
      metabolism has been proposed as a primary cause. This can be result of a trophic
      malformation of cerebral sympathetic nervous system. Possible factors that are
      involved in the pathogenesis are trauma, viral infections, heredity, endocrine
      disturbances, and autoimmunity, among others. Characteristically, atrophy
      progresses slowly for several years and, soon after, it become stable. The
      purpose of this work is, through the presentation of a clinical case, to
      accomplish a literature review concerning general characteristics, etiology,
      pathophysiology, differential diagnosis, and treatment of progressive hemifacial
      atrophy.

PMID- 22629074
TI  - Reliability of permanent mandibular first molars and incisors widths as predictor
      for the width of permanent mandibular and maxillary canines and premolars.
AB  - AIM: Preventive measures are necessary to prevent a potential irregularity from
      progressing into a more severe malocclusion. The determination of the tooth size
      arch length discrepancy in mixed dentition requires an accurate prediction of the
      mesiodistal widths of the unerupted permanent teeth. MATERIALS AND METHODS: For
      the study, 200 subjects in the age group of 16-25 years were selected from
      various colleges of M. M. University. The mesiodistal width of permanent
      mandibular incisors, first molars, canines and premolars of both arches were
      measured on the subject cast using an electronic digital caliper. Statistical
      analysis showed a significant difference between mesiodistal tooth widths of
      males and females. Linear regression equation was determined to predict the sum
      of mandibular and maxillary permanent canines and premolars using mandibular
      first molars plus the four mandibular incisors as predictors. RESULTS: There was
      no significant difference between the actual and predicted width of sum of
      permanent canines and premolars using regression equations. The predicted widths
      of both arches using Tanaka and Johnston equations showed significant
      differences. Determined regression equations for males were accurate in male
      samples and determined regression equation for females were accurate in female
      samples for both arches.

PMID- 22629075
TI  - Aesthetic approach for anterior teeth with enamel hypoplasia.
AB  - Enamel hypoplasia is a developmental defect of the enamel that is produced by a
      disturbance in the formation of the organic enamel matrix, clinically visible as
      enamel defects. Disorders that occur during the stages of enamel development and
      maturation reduce the amount or thickness of the enamel, resulting in white
      spots, tiny grooves, depressions and fissures in the enamel surface. The
      complexity and intensity of the dental deformity lesions will conduct the ideal
      treatment-associating conservative techniques. This article presents a case
      report of a restorative treatment of enamel hypoplasia using hybrid composite
      resin to mask color alteration and enamel defects. An aesthetic appearance that
      respects the tooth polychromatic and the self-esteem of the patient can be
      achieved with this approach.

PMID- 22629076
TI  - Aesthetic and functional management of a patient with Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome is a syndrome of multiple congenital anomalies. The
      genetic and molecular bases of these lesions are not clear. It is divided into
      three types based on the severity of the anomaly. Dental findings revealed
      contracted maxilla, malaligned teeth, multiple impacted and missing teeth. This
      article describes the successful management of upper central incisor with lateral
      opening in the apical third on the mesial surface of the root along with
      aesthetic and functional rehabilitation.

PMID- 22629077
TI  - Endodontic treatment and esthetic management of a primary double tooth with
      direct composite using silicone buildup guide.
AB  - Gemination and fusion are morphological dental anomalies, characterized by the
      formation of a clinically wide tooth. Gemination occurs when one tooth bud tries
      to divide, while fusion occurs if two buds unite. The terms double teeth, double
      formation, conjoined teeth, geminifusion, vicinifusion and dental twinning are
      often used to describe fusion and gemination. Double teeth are associated with
      clinical problems such as poor esthetics, spacing problems and caries
      susceptibility. Management of such cases requires a comprehensive knowledge of
      the clinical entity as well as the problems associated with it. This report
      presents a case of primary double tooth in a 6-year-old boy involving maxillary
      left central incisor. The anomalous tooth was carious and pulpally involved. This
      was treated conservatively by endodontic treatment and esthetic rehabilitation
      was done with direct composite restoration using a silicone buildup guide. The
      treated tooth was followed up until exfoliation.

PMID- 22629078
TI  - X-linked ichthyosis along with epidermolysis bullosa.
AB  - Ichthyoses are a heterogenous group of hereditary keratinization disorders that
      share in common the accumulation & shedding of large amounts of hyperkeratotic
      epidermis. Early reports of ichthyosis in the Indian and Chinese literature date
      back to several hundred years. X-linked recessive ichthyosis (XLI) is a common
      disorder of keratinization and affects males who inherit an X-chromosome having a
      steroid sulphatase genetic mutation. In the present communication we report a
      case of XLI and dystrophic epidermolysis bullosa in the same patient. To the best
      of our knowledge it has been reported only once before.

PMID- 22629079
TI  - Agenesis of premolar associated with submerged primary molar and a supernumerary
      premolar: An unusual case report.
AB  - The combination of submerged primary molar, agenesis of permanent successor with
      a supernumerary in the same place is very rare. The purpose of this article is to
      report a case of submerged mandibular left second primary molar with
      supernumerary tooth in the same region along with agenesis of second premolar in
      an 11-year-old girl, its possible etiological factors, and a brief discussion on
      treatment options.

PMID- 22629080
TI  - Clinical trial ethics in India: One step forward, two steps back.

PMID- 22629081
TI  - Pharmacotherapy for multidrug resistant tuberculosis.
AB  - The current global concern in the treatment of tuberculosis (TB) is the emergence
      of resistance to the two most potent drugs namely, isoniazid and rifampicin.
      Emergence of multidrug resistance tuberculosis (MDR-TB) is now a health problem
      faced by most of the developing countries as well as developed countries across
      the globe. MDR-TB is a man-made disease that is caused by improper treatment,
      inadequate drug supplies, and poor patient supervision. HIV infection and AIDS
      have been implicated as important cause for this. The review of a published
      literature suggests that the most powerful predictor of treatment of MDR-TB is a
      history of treatment of TB. Although the treatment is efficacious, there are also
      a number of adverse effects caused by drugs used in the treatment of MDR-TB.

PMID- 22629082
TI  - A review of antihistamines used during pregnancy.
AB  - Antihistamines are one of the most common drugs that are used extensively in
      various dermatological and nondermatological conditions. The use of H-1
      antihistamines during pregnancy has been very controversial due to possible
      teratogenic effects of these drugs. None of the antihistamines available today
      have been categorized as safe during pregnancy. Control studies are available for
      certain first generation drugs regarding their safety in pregnancy, but the newer
      agents require further studies to be declared safer in pregnancy. A few drugs are
      comparatively safer to use in pregnancy than others. Every drug used in pregnancy
      carries a risk for teratogenicity and careful risk/benefit assessment should be
      done before prescribing them.

PMID- 22629083
TI  - Ulipristal acetate, a progesterone receptor modulator for emergency
      contraception.
AB  - Unwanted pregnancy is a global reproductive health problem. Emergency
      contraception is defined as the use of drug or device after unprotected or
      underprotected intercourse to prevent an unwanted pregnancy. 1.5 mg of
      levonorgestrel as a single dose or in two doses with 12 h apart taken within 72 h
      of unprotected intercourse is the current gold standard emergency contraception
      regimen. This method is only effective if used as soon as possible after sexual
      intercourse and before ovulation. A single dose of 30 mg ulipristal acetate, a
      novel selective progesterone receptor modulator, has recently been proposed for
      the emergency contraception use up to 120 h of unprotected intercourse with
      similar side effect profiles as levonorgestrel. Ulipristal acetate could possibly
      prevent pregnancy when administered in the advanced follicular phase, even if
      luteinizing hormone levels have already begun to rise, a time when levonorgestrel
      is no longer effective in inhibiting ovulation.

PMID- 22629084
TI  - Epilepsy: Novel therapeutic targets.
AB  - Despite of established and effective therapy for epilepsy, 20-25% patients
      develop therapeutic failure; this encourages finding newer drugs. Novel
      approaches target receptors which remain unaffected by conventional therapy or
      inhibit epileptogenesis. AMPA receptor antagonists have shown faster and complete
      protection compared to diazepam. Protein kinase (PK) plays an important role in
      the development of epilepsy. PK inhibitors such as K252a, VID-82925, and
      Herbimycin A have been found effective in inhibition of spread of epileptiform
      activity and epileptogenesis. Metabotropic glutamate receptors (mGluRs) are G
      protein-coupled receptors classified into three groups. Group 1 mGluRs antagonist
      and Groups 2 and 3 mGluRs agonists inhibited pentylenetetrazole-induced kindled
      seizures. Combined use of these agents has also shown favorable results.
      Mammalian target of rapamycin (mTOR) plays a central role in multiple mechanisms
      of epileptogenesis. mTOR causes transcription, induction of proapoptotic
      proteins, and autophagy inhibition. Rapamycin was effective in suppression of
      recurrent seizures as well as in tuberous sclerosis and acute brain injury model.
      5% CO(2) showed potent effects on cortical epileptiform activity and convulsions
      in animal epilepsy models and in humans with drug-resistant partial epilepsy. It
      is found to be rapidly acting, safe and cheap, thus it can be a good option in
      emergency for suppression of seizure. Neurosteroids are considered as fourth
      generation neuromessengers, they act as positive allosteric modulators of gamma
      aminobutyric acid (GABAA) receptors. Clinical trial of ganaxolone, an
      allopregnanolone analogue, has shown a beneficial role in pharmacoresistant
      epilepsy. However, most of these drugs are tested in early phases of development
      and the possible use and safety in epilepsy has to be proven in clinical trials.

PMID- 22629085
TI  - Vitamin D: The "sunshine" vitamin.
AB  - Vitamin D insufficiency affects almost 50% of the population worldwide. An
      estimated 1 billion people worldwide, across all ethnicities and age groups, have
      a vitamin D deficiency (VDD). This pandemic of hypovitaminosis D can mainly be
      attributed to lifestyle (for example, reduced outdoor activities) and
      environmental (for example, air pollution) factors that reduce exposure to
      sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production
      in the skin. High prevalence of vitamin D insufficiency is a particularly
      important public health issue because hypovitaminosis D is an independent risk
      factor for total mortality in the general population. Current studies suggest
      that we may need more vitamin D than presently recommended to prevent chronic
      disease. As the number of people with VDD continues to increase, the importance
      of this hormone in overall health and the prevention of chronic diseases are at
      the forefront of research. VDD is very common in all age groups. As few foods
      contain vitamin D, guidelines recommended supplementation at suggested daily
      intake and tolerable upper limit levels. It is also suggested to measure the
      serum 25-hydroxyvitamin D level as the initial diagnostic test in patients at
      risk for deficiency. Treatment with either vitamin D2 or vitamin D3 is
      recommended for deficient patients. A meta-analysis published in 2007 showed that
      vitamin D supplementation was associated with significantly reduced mortality. In
      this review, we will summarize the mechanisms that are presumed to underlie the
      relationship between vitamin D and understand its biology and clinical
      implications.

PMID- 22629086
TI  - Red carpeting the newer antidiabetics.
AB  - The rapidly increasing prevalence of diabetes on a global scale beseeches an
      urgent need for newer and better treatment options. Our better understanding of
      the pathophysiology of diabetes has enabled a continual churn out of newer
      antidiabetic agents with varying modes of action. Sodium-Glucose Transport
      Proteins-2 inhibitors, dipeptidyl peptidase IV inhibitors, glucagon-like peptide
      analogues, glucokinase activators, dual peroxisome proliferator-activated
      receptor agonists, monoclonal antibodies, and dopamine-2 receptor agonists either
      as monotherapy or combination therapy with the existing oral hypoglycemic agents
      compound our fight against diabetes. A review of the newer drugs targeting
      various aspects in the management of diabetes is presented.

PMID- 22629087
TI  - Effect of rolipram, a phosphodiesterase enzyme type-4 inhibitor, on gamma-amino
      butyric acid content of the frontal cortex in mice exposed to chronic mild
      stress.
AB  - OBJECTIVES: To investigate the alterations in GABA levels by rolipram in the
      model of depression. MATERIALS AND METHODS: The alteration of GABA content by
      rolipram as a phosphodiesterase enzyme type-4 inhibitor in the frontal cortex
      (FCx; as a brain region crucial for the control of emotion and cognition)
      obtained from male mice exposed to chronic mild stress (CMS)-induced anhedonia
      (the loss of pleasure or lack of sensitivity to pleasure stimuli) was recorded.
      RESULTS: The results demonstrated the reversal of CMS-induced anhedonia after 3
      weeks per os of rolipram in a dose of 0.1 mg/kg/day dissolved in distilled water.
      Furthermore, rolipram showed a significant reduction in duration of immobility in
      long-term behavioral changes recorded by the FST. Additionally, there was a
      significant increase in the GABA content of the FCx of rolipram-treated mice
      exposed to CMS-induced anhedonia. CONCLUSIONS: The present study suggested that
      GABA levels may be decreased in an animal model of depression and its reversal
      together with the behaviour improvement by rolipram could support the hypothesis
      that modification in GABAergic activity has a role in mood disorders. These
      effects may complement the antidepressant effect of rolipram that is originally
      mediated via inhibition of phosphodiesterase enzyme type-4 [PDE4] that increases
      cyclic adenosine monophosphate signalling the pharmacotherapy of depression.

PMID- 22629088
TI  - Patient factors impacting antiretroviral drug adherence in a Nigerian tertiary
      hospital.
AB  - OBJECTIVE: To study the adherence levels and explore factors impacting them in
      out-patients on antiretroviral therapy (ART) at the AIDS Prevention Initiative in
      Nigeria antiretroviral clinic of the Jos University Teaching Hospital. MATERIALS
      AND METHODS: We administered a structured questionnaire to 461 patients
      presenting to the clinic. Adherence was measured using the patient self-report.
      The association between independent variables and adherence to ART was measured
      through odd ratios (OR) in the univariate analysis. The best predictors of
      adherence were determined through multiple logistic regression models with
      backward elimination. RESULTS: The adherence level was found to be 87.9%. The
      following factors were found to have strong impact on adherence in the univariate
      analysis: age (OR 1.04), sex (OR 1.14), employment (OR 1.29), knowledge of HIV
      (OR 1.11), thrice daily frequency of drug intake (OR 1.68), twice daily frequency
      (OR 2.18), alcohol nonintake (OR 0.29), knowledge of ARVs (OR 1.23), pill burden
      (OR 1.20), and HIV status disclosure (OR 1.08). In the multivariate analysis,
      only age, alcohol nonintake and twice daily, frequency of drug intake affected
      adherence (P < 0.05). CONCLUSIONS: To increase adherence and the effectiveness of
      ART, there is need to continuously emphasize the use of adherence devices and
      reminders. Counseling and adherence education should also be emphasized
      especially for younger patients and those with low educational levels.

PMID- 22629089
TI  - Cardiorenal benefits of early versus late cyclosporine to sirolimus conversion in
      a rat model.
AB  - OBJECTIVE: To compare the cardiorenal effects of early versus late cyclosporine
      (CsA) to sirolimus (SRL) conversion, using a novel animal model that mimics these
      protocols used in the clinical practice, and focusing on blood pressure, heart
      rate (HR), biochemical data and heart and kidney lipid peroxidation. MATERIALS
      AND METHODS: The study had five groups. Six male Wistar rats in each group were
      used during a 9-week study protocol: control, CsA (5 mg/kg/day), SRL (1
      mg/kg/day); early conversion and late conversion. Cardiorenal evaluation was
      assessed by biochemical data, blood pressure, HR, and heart and kidney lipid
      peroxidation. RESULTS: As expected, CsA promoted cardiorenal impairment, viewed
      by development of hypertension, tachycardia, increased urea, creatine kinase, and
      glucose levels, as well as heart and kidney oxidative stress. SRL, as expected,
      promoted less cardiorenal side effects, namely those related with nephrotoxicity.
      In agreement, both early and late conversions from CsA to SRL produced less side
      effects, namely those related to the CsA-induced nephrotoxicity. CONCLUSIONS: In
      our model, both early and late CsA to SRL conversion promoted amelioration of the
      CsA -induced cardiorenal damage. However, early substitution seems to produce
      more benefits, in particular due to higher improvement of the cardiac profile.

PMID- 22629090
TI  - Hepatoprotective activities of picroliv, curcumin, and ellagic acid compared to
      silymarin on carbon-tetrachloride-induced liver toxicity in mice.
AB  - INTRODUCTION: To evaluate the hepatoprotective activity of active phytochemicals,
      picroliv, curcumin, and ellagic acid in comparison to silymarin in the mice model
      of carbon tetrachloride (CCl(4)) induced liver toxicity. In addition, attempts
      were made to elucidate their possible mechanism(s) of action. MATERIALS AND
      METHODS: Oxidative stress was induced in Swiss albino mice by a single injection
      (s.c.) of CCl(4), 1 ml/kg body weight, diluted with arachis oil at a 1:1 ratio.
      The phytochemicals were administered once a day for 7& days (p.o.) as
      pretreatment at two dose levels (50 and 100 mg/kg/day). RESULTS: CCl(4)-induced
      hepatotoxicity was manifested by an increase in the activities of liver enzymes
      (alanine transaminase, P < 0.001, aspartate transaminase, P < 0.001 and alkaline
      phosphatase, P < 0.001), malondialdehyde (MDA, P < 0.001)) levels and a decrease
      in activity of reduced glutathione (P < 0.001) and catalase in liver tissues. The
      histopathological examination of liver sections revealed centrizonal necrosis,
      fatty changes, and inflammatory reactions. The pretreatment with picroliv,
      curcumin, and ellagic acid normalized serum aminotransferase activities (P <
      0.001), decreased levels of MDA (P < 0.001), improved the antioxidant status, and
      normalized the hepatic histo-architecture. The restoration of phenobarbitone
      induced sleeping time also suggested the normalization of liver cytochrome P450
      enzymes. CONCLUSION: This study supports the use of these active phytochemicals
      against toxic liver injury, which may act by preventing lipid peroxidation,
      augmenting the antioxidant defense system or by regenerating the hepatocytes.

PMID- 22629091
TI  - Association between altered thyroid state and insulin resistance.
AB  - OBJECTIVE: To determine the association between altered thyroid hormones and
      insulin resistance (IR). MATERIALS AND METHODS: Eight euthyroid (EU), eight
      hypothyroid (HO), and eight hyperthyroid (HR) patients with no past medical
      history were studied in this cross-sectional study at the Care Institute of
      Medical Sciences, Ahmedabad, India, The fasting blood sample were analyzed for
      thyroid stimulating hormone (TSH), lipid profile, insulin, and glucose.
      Homeostatic model assessment (HOMA) was calculated for assessing IR. RESULTS:
      HOMA values were significantly higher in HR and HO groups as compared to the EU
      group (P < 0.05). Insulin levels were also found to be significantly increased in
      HR and HO groups as compared to the EU group (P < 0.05). Cholesterol,
      triglycerides (TG), and low density lipoprotein (LDL) were significantly raised
      in HO as compared to EU and HR groups (P < 0.05) whereas high density lipoprotein
      levels (HDL) were lower. HOMA and insulin were found to be positively correlated
      with TSH in HO and negatively in HR. CONCLUSION: Thyroid disorder, including both
      hypo- and hyper have been associated with IR due to various mechanisms such as
      altered insulin secretion and lipid levels. IR was comparable in patients with
      both HO and HR. Although HO and HR constitute an IR state, more studies need to
      be done in order to clarify the underlying pathogenic mechanism. Thus, an altered
      thyroid state can lead to IR leading to glucose-related disorder such as diabetes
      dyslipidemia.

PMID- 22629092
TI  - Cortico-hippocampal salvage in chronic aluminium induced neurodegeneration by
      Celastrus paniculatus seed oil: Neurobehavioural, biochemical, histological
      study.
AB  - OBJECTIVE: To investigate the effects of Celastrus paniculatus seed oil in
      preventing the onset of chronic aluminum induced cortico-hippocampal
      neurodegeneration and oxidative stress. MATERIALS AND METHODS: An animal model of
      senile dementia of Alzheimer's type was produced by administering aluminum as
      aluminum chloride (4.2 mg/kg) intraperitoneally to male Wistar rats for 60 days
      and results compared to untreated control. Neurobehavioral investigations of
      Morris water maze tests, passive avoidance test, rotarod test and biochemical
      estimations of acetylcholineterase, malondialdehyde, glucose-6-phosphate
      dehydrogenase, superoxide dismutase, and hemoglobin in blood were performed
      fortnightly which gauged the extent of global oxidative stress and progressive
      neural damage. Findings were fortified by the above enzyme assays and histology
      of brain at necropsy. Prophylactic oral C. paniculatus in two doses 0.5 ml and 1
      ml, were given to animals and the results were analyzed in comparison to a
      similar rodent model with standard drug donepezil (0.5 mg/kg) intraperitoneally.
      RESULTS: C. paniculatus showed a significant prevention in onset of aluminum
      induced neural insult and overall systemic oxidative stress which was
      corroborated by the enlisted neurobehavioral, biochemical, and histological
      evidence. CONCLUSION: C. paniculatus is a putative decelerator of Al-mediated
      Alzheimer's like pathobiology.

PMID- 22629093
TI  - Measurement of invasive blood pressure in rats.
AB  - Blood pressure (BP) is one of the vital parameters used to assess the
      cardiovascular functions of a mammal. BP is commonly recorded using invasive,
      noninvasive, and radio telemetry methods, but invasive blood pressure (IBP)
      recording is considered the gold standard. IBP provides a direct indication of
      the effect of the investigational products on the circulatory system. Recording
      the IBP in rodents is an essential part of the preliminary screening of any
      product to determine its effect on the cardiovascular system. The present article
      describes the measurement of the IBP in Wistar rats/Sprague Dawley rats.

PMID- 22629094
TI  - The basic concepts of scientific research and scientific communication.

PMID- 22629095
TI  - Evaluation of protective effect of Butea monosperma (lam.) Taub in experimental
      hepatotoxicity in rats.

PMID- 22629096
TI  - Antiulcer screening of Carthamus tinctorius on volume and acidity of stimulated
      gastric secretion in rats.

PMID- 22629097
TI  - Protective effects of apigenin against methyl methanesulfonate induced hsp70
      expression in the third instar larvae of transgenic Drosophila melanogaster
      (hsp70-lacZ)Bg(9).

PMID- 22629098
TI  - Antibiotic prescribing pattern in ophthalmology outpatient department in a
      tertiary care hospital.

PMID- 22629099
TI  - Effect of Stereospermum tetragonum DC. in alloxan induced diabetic rats.

PMID- 22629100
TI  - L-Asparginase induced cortical venous thrombosis in a patient with acute
      leukemia.
AB  - L-Asparginase is used for remission induction in acute lymphoblastic leukemia. We
      describe a case of 16-year-old boy who developed cortical venous thrombosis
      following the administration of L-Asparginase.

PMID- 22629102
TI  - Docetaxel-induced hand foot syndrome: "No dose is a safe dose".
AB  - Docetaxel is an important chemotherapeutic agent used in the management of many
      solid tumors. The most important side effect of this drug is myelosupression. We
      report a case of carcinoma breast that developed severe hand-foot syndrome at 75
      mg/m(2) doses of docetaxel. The exact mechanism of this side effect in not known.
      All the physicians using this drug must be aware of this side effect.

PMID- 22629101
TI  - Ethionamide-induced gynecomastia.
AB  - Gynecomastia is very rare during antituberculosis chemotherapy. We describe a 38
      year-old male patient who developed a painful gynecomastia following second-line
      drug therapy for multidrug-resistant pulmonary tuberculosis. Gynecomastia
      disappeared after stopping the ethionamide. A published literature on
      antituberculosis-induced gynecomastia is also briefly discussed.

PMID- 22629103
TI  - Carbamazepine-induced erythema multiforme major in an epileptic patient with
      bipolar affective disorder.
AB  - Carbamazepine (CBZ) is frequently used for epilepsy and various psychiatric
      illnesses. It is known for its dermatological side effects which may range from
      mild rash to life-threatening reactions as Stevens Johnson syndrome or toxic
      epidermal necrolysis. We hereby report a rare case of 17-year-old woman suffering
      from generalized tonic clonic epilepsy with comorbid bipolar affective disorder,
      who was initially treated with sodium valproate with partial improvement. After
      19 days of addition of CBZ to the therapy, the patient developed erythema
      multiforme major with >60% skin involvement and oral, conjunctival, intestinal,
      and vaginal mucosal involvement.

PMID- 22629104
TI  - Problem solving interactive clinical seminars for undergraduates.

PMID- 22629105
TI  - Is gripe water baby-friendly?

PMID- 22629106
TI  - Clinical trials toolkit.

PMID- 22629107
TI  - Boceprevir: A new hope against hepatitis C virus.

PMID- 22629108
TI  - A Physics-driven Neural Networks-based Simulation System (PhyNNeSS) for
      multimodal interactive virtual environments involving nonlinear deformable
      objects.
AB  - BACKGROUND: While an update rate of 30 Hz is considered adequate for real time
      graphics, a much higher update rate of about 1 kHz is necessary for haptics.
      Physics-based modeling of deformable objects, especially when large nonlinear
      deformations and complex nonlinear material properties are involved, at these
      very high rates is one of the most challenging tasks in the development of real
      time simulation systems. While some specialized solutions exist, there is no
      general solution for arbitrary nonlinearities.  METHODS: In this work we present
      PhyNNeSS - a Physics-driven Neural Networks-based Simulation System - to address
      this long-standing technical challenge. The first step is an off-line pre
      computation step in which a database is generated by applying carefully
      prescribed displacements to each node of the finite element models of the
      deformable objects. In the next step, the data is condensed into a set of
      coefficients describing neurons of a Radial Basis Function network (RBFN). During
      real-time computation, these neural networks are used to reconstruct the
      deformation fields as well as the interaction forces.  RESULTS: We present
      realistic simulation examples from interactive surgical simulation with real time
      force feedback. As an example, we have developed a deformable human stomach model
      and a Penrose-drain model used in the Fundamentals of Laparoscopic Surgery (FLS)
      training tool box.  CONCLUSIONS: A unique computational modeling system has been
      developed that is capable of simulating the response of nonlinear deformable
      objects in real time. The method distinguishes itself from previous efforts in
      that a systematic physics-based pre-computational step allows training of neural
      networks which may be used in real time simulations. We show, through careful
      error analysis, that the scheme is scalable, with the accuracy being controlled
      by the number of neurons used in the simulation. PhyNNeSS has been integrated
      into SoFMIS (Software Framework for Multimodal Interactive Simulation) for
      general use.

PMID- 22629109
TI  - Viewing Cognitive Conflicts as Dilemmas: Implications for Mental Health.
AB  - The idea that internal conflicts play a significant role in mental health has
      been extensively addressed in various psychological traditions, including
      personal construct theory. In the context of the latter, several measures of
      conflict have been operationalized using the Repertory Grid Technique (RGT). All
      of them capture the notion that change, although desirable from the viewpoint of
      a given set of constructs, becomes undesirable from the perspective of other
      constructs. The goal of this study is to explore the presence of cognitive
      conflicts in a clinical sample (n = 284) and compare it to a control sample (n =
      322). It is also meant to clarify which among the different types of conflict
      studied provides a greater clinical value and to investigate its relationship to
      symptom severity (SCL-90-R). Of the types of cognitive conflict studied,
      implicative dilemmas were the only ones to discriminate between clinical and
      nonclinical samples. These dilemmas were found in 34% of the nonclinical sample
      and in 53% of the clinical sample. Participants with implicative dilemmas showed
      higher symptom severity, and those from the clinical sample displayed a higher
      frequency of dilemmas than those from the nonclinical sample.

PMID- 22629110
TI  - Cognitive Factors in Fibromyalgia: The Role of Self-Concept and Identity Related
      Conflicts.
AB  - Fibromyalgia is a syndrome characterized by the presence of diffuse and chronic
      musculoskeletal pain of unknown etiology. Clinical diagnosis and the merely
      palliative treatments considerably affect the patient's experience and the
      chronic course of the disease. Therefore, several authors have emphasized the
      need to explore issues related to self in these patients. The repertory grid
      technique (RGT), derived from personal construct theory, is a method designed to
      assess the patient's construction of self and others. A group of women with
      fibromyalgia (n = 30) and a control group (n = 30) were assessed using RGT. Women
      with fibromyalgia also completed the Fibromyalgia Impact Questionnaire and a
      visualanalogue scale for pain, and painful tender points were explored. Results
      suggest that these women had a higher present self-ideal self discrepancy and a
      lower perceived adequacy of others, and it was more likely to find implicative
      dilemmas among them compared to controls. These dilemmas are a type of cognitive
      conflict in which the symptom is construed as "enmeshed" with positive
      characteristics of the self. Finally, implications of these results for the
      psychological treatment of fibromyalgia are suggested to give a more central role
      to self-identity issues and to the related cognitive conflicts.

PMID- 22629111
TI  - New Treatments for Rhabdomyosarcoma: the Importance of Target Practice.
AB  - To address the poor outcomes in rhabdomyosarcoma, particularly the alveolar
      subtype, new therapies are needed. Potential cancer-specific alterations that may
      be molecular targets include gene fusions or copy number changes. Following the
      latter strategy, an attractive antigene approach was developed to inhibit MYCN
      oncogene expression in rhabdomyosarcoma.

PMID- 22629112
TI  - Prospective evaluation of simply modified MODS assay: an effective tool for TB
      diagnosis and detection of MDR-TB.
AB  - BACKGROUND AND SETTING: Thailand is one of the highest tuberculosis (TB)-burdened
      countries. Chiang Rai, the northernmost province of Thailand has high
      tuberculosis and human immunodeficiency virus (HIV) prevalence and the laboratory
      workload for TB culture and drug susceptibility testing is increasing.
      OBJECTIVES: To evaluate the simply modified microscopic-observation drug
      susceptibility assay (MODS) in the setting of a developing country. METHODS: In
      this cross-sectional diagnostic study, a total of 202 sputum samples of
      clinically diagnosed TB patients were used to test the performance of MODS assay
      in reference to gold standard BACTECTM MGITTM 960 liquid culture system and Ogawa
      solid culture. Sputum samples were collected from clinically diagnosed TB
      patients. Culture growth rate and time to culture positivity were compared among
      three methods. Performance of modified MODS assay was evaluated for detection of
      mycobacterium drug resistance in reference to MGIT antimicrobial susceptibility
      test (AST). RESULT: Median time to culture positivity by MODS, solid, and liquid
      culture were 12, 30, and 6 days respectively. Compared to the drug susceptibility
      test (DST) result of reference liquid culture, the sensitivity and specificity of
      MODS for detection of multidrug-resistant tuberculosis (MDR-TB) was 85.7% and
      97.5% respectively. MODS assay has a positive predicative value of 80% and
      negative predictive value of 96.5% for isoniazid resistance, 70% and 100% for
      rifampicin resistance, and 66.7% and 99.1% for MDR-TB. CONCLUSION: MODS is a
      highly effective screening test for detection of MDR-TB.

PMID- 22629113
TI  - Economic evaluation of intravenous iron treatments in the management of anemia
      patients in Greece.
AB  - PURPOSE: To conduct an economic evaluation comparing Ferinject((r)) (ferric
      carboxymaltose [FCM]) with Venofer((r)) (iron sucrose [IS]) and CosmoFer((r))
      (low-molecular-weight iron dextran [LMWID]) in the management of iron deficiency
      anemia in Greece. PATIENTS AND METHODS: A cost-minimization analysis was
      conducted since there are no clear data indicating that one of these regimens is
      superior to the others in terms of efficacy. Main data inputs were based on
      bibliography and validated by clinicians. The economic evaluation was conducted
      for inpatients (ie, surgical patients or patients hospitalized due to a disease
      related to chronic or acute blood loss) and outpatients (eg, nondialysis chronic
      kidney disease patients), separately. Analysis was carried out from a National
      Health Service (NHS) perspective and also from a patient perspective. Total cost
      treatment reflects the cost of drugs, the cost of all resources expended in
      patient management such as the cost of disposables for each infusion, the
      monitoring costs during infusion (salaries of personnel), other hospital
      expenses, the cost for management of adverse events, the productivity loss, and
      the traveling cost for patients. RESULTS: In the case of outpatients, the mean
      total cost per patient in the FCM arm was ?198.6, in the IS arm ?627.7, and in
      the LMWID arm, ?510.5. For inpatients the mean total cost was estimated at ?189.2
      for FCM while it was ?419.9 and ?228.8 for IS and LMWID, respectively. Budget
      impact analysis for a typical Greek hospital with 100 patients revealed that the
      total cost of FCM (inpatients analysis) was 113% and 15.4% lower against their
      comparators. In an outpatient situation, the total cost of FCM was 201.1% and
      151.8% lower compared with IS and LMWID, respectively. CONCLUSION: Ferric
      carboxymaltose may represent a cost-saving option compared with the most likely
      alternative existing therapies used for the management of anemia in the National
      Health Service of Greece.

PMID- 22629114
TI  - Gelatin tannate reduces the proinflammatory effects of lipopolysaccharide in
      human intestinal epithelial cells.
AB  - BACKGROUND: Gelatin tannate is a mixture of tannic acid and gelatin. Tannic acid
      has astringent properties, due to its capacity to form protein-macromolecular
      complexes, as well as antibacterial and antioxidant properties. However, little
      is known about its anti-inflammatory properties. PURPOSE: To evaluate the anti
      inflammatory activity of gelatin tannate by quantifying the suppression of key
      molecules produced during inflammatory events in lipopolysaccharide (LPS)
      stimulated human intestinal cells. METHODS: Intercellular adhesion molecule-1
      (ICAM-1) expression was determined by Western blot analysis; interleukin-8 (IL-8)
      and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured by
      enzyme-linked immunosorbent assays in Caco-2 cells 24 hours after treatment with
      LPS (1 MUg/mL) in presence of different concentrations of gelatin tannate.
      RESULTS: ICAM-1 is induced on a wide variety of cells by inflammatory stimuli
      such as LPS. Our results have shown gelatin tannate as a potent inhibitor of ICAM
      1 expression in LPS-stimulated Caco-2 cells. IL-8 and TNF-alpha are important
      inflammatory mediators, recruiting neutrophils and T-lymphocytes. Together with
      LPS, adding gelatin tannate at different concentrations induced a dose-dependent
      inhibition of IL-8 and TNF-alpha released by Caco-2 cells. CONCLUSION: These
      results suggest that gelatin tannate exerts anti-inflammatory effects by
      inhibiting the specific cytokines and adhesion molecules involved in several
      inflammatory disorders.

PMID- 22629115
TI  - Cultural differences in acceptability of a vaginal microbicide: a comparison
      between potential users from Nashville, Tennessee, USA, and Kafue and Mumbwa,
      Zambia.
AB  - PURPOSE: We sought to determine the relationship between acceptability of a
      hypothetical vaginal microbicide, cultural factors, and perceived HIV risk among
      African-American women in Nashville, TN, USA, and African women in Kafue and
      Mumbwa, Zambia. PATIENTS AND METHODS: Women in both sites completed a survey.
      Regression analyses were performed on valid samples (Nashville, 164; Zambia, 101)
      to determine cultural differences affecting microbicide acceptability. Regression
      analyses also tested whether individual risk perception affected acceptability.
      RESULTS: In Zambia, 89.6% of women were willing to use a microbicide versus 81.6%
      in Nashville (P < 0.0001). One cultural difference is that women in the Zambian
      cohort viewed risk of HIV infection as distinct from risk of acquiring STIs, with
      48% believing they were certain to become infected with AIDS, compared to 4% of
      Nashville participants. CONCLUSION: These results suggest a high degree of
      acceptability toward use of a vaginal microbicide to prevent HIV infection.

PMID- 22629116
TI  - Close association between A118G single nucleotide polymorphism and opioid,
      alcohol, and nicotine dependence.

PMID- 22629117
TI  - 7-Nitroindazole and its rapidly emerging role in opioid pain management and
      withdrawal.

PMID- 22629118
TI  - Infection dynamics of western equine encephalomyelitis virus (Togaviridae:
      Alphavirus) in four strains of Culex tarsalis (Diptera: Culicidae): an
      immunocytochemical study.
AB  - BACKGROUND: Vector competence describes the efficiency with which vector
      arthropods become infected with and transmit pathogens and depends on
      interactions between pathogen and arthropod genetics as well as environmental
      factors. For arbovirus transmission, the female mosquito ingests viremic blood,
      the virus infects and replicates in midgut cells, escapes from the midgut, and
      disseminates to other tissues, including the salivary glands. Virus-laden saliva
      is then injected into a new host. For transmission to occur, the virus must
      overcome several "barriers", including barriers to midgut infection and/or escape
      and salivary infection and/or escape. By examining the spatial/temporal infection
      dynamics of Culex tarsalis strains infected with western equine encephalomyelitis
      virus (WEEV), we identified tissue tropisms and potential tissue barriers, and
      evaluated the effects of viral dose and time postingestion.  METHODS: Using
      immunostained paraffin sections, WEEV antigens were tracked in four Cx. tarsalis
      strains: two recently colonized California field strains - Coachella Valley,
      Riverside County (COAV) and Kern National Wildlife Refuge (KNWR); and two
      laboratory strains selected for WEEV susceptibility (high viremia producer, HVP),
      and WEEV resistance (WR).  RESULTS AND CONCLUSIONS: Tissues susceptible to WEEV
      infection included midgut epithelium, neural ganglia, trachea, chorionated eggs,
      and salivary glands. Neuroendocrine cells in the retrocerebral complex were
      occasionally infected, indicating the potential for behavioral effects. The HVP
      and COAV strains vigorously supported viral growth, whereas the WR and KNWR
      strains were less competent. Consistent with earlier studies, WEEV resistance
      appeared to be related to a dose-dependent midgut infection barrier, and a midgut
      escape barrier. The midgut escape barrier was not dependent upon the ingested
      viral dose. Consistent with midgut infection modulation, disseminated infections
      were less common in the WR and KNWR strains than in the HVP and COAV strains.
      Once the virus disseminated from the midgut, all strains were able to develop
      salivary gland infections. The possible roles of observed pathology will be
      discussed in a subsequent paper.

PMID- 22629119
TI  - Temperature-sensitive gels for intratumoral delivery of beta-lapachone: effect of
      cyclodextrins and ethanol.
AB  - This work evaluated the potential of Pluronics (varieties F127 and P123) in
      combination with solubilizing agents to be used as syringeable in situ gelling
      depots of intratumoral beta-lapachone (betaLAP). Pluronic dispersions prepared at
      various concentrations in the absence and the presence of ethanol and randomly
      methylated beta-cyclodextrin (RMbetaCD) were characterized regarding their
      rheological properties, drug solubilization capacity, and in vitro release.
      Pluronic F127 (18-23%) formulations combined high ability to solubilize betaLAP
      (enhancement solubility factor up to 50), adequate gel temperature range (over 25
      degrees C), and gel strength at 37  degrees C enough to guarantee the permanence
      of the formulation in the administration site for a period of time. betaLAP
      release rate was finely tuned by the concentration of the polymer and the
      addition of RMbetaCD (diffusion coefficient ranging between 9 and 69 MUg . cm(
      2)). The ethanol increases betaLAP release rate but simultaneously led to weak
      gels. This paper shows that betaLAP formulations involving temperature-reversible
      Pluronic gels may be suitable for intratumoral drug delivery purposes.

PMID- 22629120
TI  - Cognitive-behavioral therapy versus other PTSD psychotherapies as treatment for
      women victims of war-related violence: a systematic review.
AB  - Although war-trauma victims are at a higher risk of developing PTSD, there is no
      consensus on the effective treatments for this condition among civilians who
      experienced war/conflict-related trauma. This paper assessed the effectiveness of
      the various forms of cognitive-behavioral therapy (CBT) at lowering PTSD and
      depression severity. All published and unpublished randomized controlled trials
      studying the effectiveness of CBT at reducing PTSD and/or depression severity in
      the population of interest were searched. Out of 738 trials identified, 33
      analysed a form of CBTs effectiveness, and ten were included in the paper. The
      subgroup analysis shows that cognitive processing therapy (CPT), culturally
      adapted CPT, and narrative exposure therapy (NET) contribute to the reduction of
      PTSD and depression severity in the population of interest. The effect size was
      also significant at a level of 0.01 with the exception of the effect of NET on
      depression score. The test of subgroup differences was also significant,
      suggesting CPT is more effective than NET in our population of interest. CPT as
      well as its culturallyadapted form and NET seem effective in helping war/conflict
      traumatised civilians cope with their PTSD symptoms. However, more studies are
      required if one wishes to recommend one of these therapies above the other.

PMID- 22629121
TI  - Prognostic significance of serum proangiogenic molecules in patients with de novo
      non-Hodgkin lymphomas.
AB  - This study was aimed to assess the clinical significances of the serum VEGF and
      bFGF in Thai patients with de novo NHL. Serum VEGF and bFGF concentrations were
      measured from 79 adult patients with newly diagnosed stage 2-4 non-Hodgkin
      lymphomas by quantitative sandwich enzyme immunoassay. At the time of diagnosis,
      the serum VEGF concentrations from 79 patients ranged from 72.0 to 2919.4 pg/mL,
      with a mean of 668.0 pg/dL. The serum bFGF concentrations ranged from
      undetectable to 2919.4 pg/mL, with a mean of 12.15 pg/dL. Multivariate analysis
      identified higher than the mean of serum VEGF, B symptoms, bulky diseases,
      anemia, and treatment with CHOP or R-CHOP as independent variables influencing
      the complete remission rate. From a Cox proportional hazards model, variables
      independently associated with overall survival were bone marrow involvement, more
      extranodal involvement, poor performance status, anemia, and higher than the mean
      of serum bFGF.

PMID- 22629122
TI  - Molecular markers of dental pulp tissue during orthodontic tooth movement: a
      pilot study.
AB  - Three specific orthodontic tooth movement genes, that is, FCRL1, HSPG2, and LAMB2
      were detected at upper first premolar (with appliance) dental pulp tissue by
      using GeneFishing technique as compared to lower first premolar (without
      appliance). These three differentially expressed genes have the potential as
      molecular markers during orthodontic tooth movement by looking at molecular
      changes of pulp tissue.

PMID- 22629123
TI  - The study of release of chlorhexidine from preparations with modified
      thermosensitive poly-N-isopropylacrylamide microspheres.
AB  - The aim of this study was to investigate and compare the release rates of
      chlorhexidine (CX) base entrapped in the polymeric beads of modified poly-N
      isopropylacrylamides (pNIPAMs) at temperatures below and over the volume phase
      transition temperature (VPTT) of synthesized polymers: pNIPAM-A with terminal
      anionic groups resulting from potassium persulfate initiator, pNIPAM-B with
      cationic amidine terminal groups, and pNIPAM-C comprising anionic terminals, but
      with increased hydrophobicity maintained by the N-tert-butyl functional groups.
      The preparations, assessed in vitro below the VPTT, release an initial burst of
      CX at different time periods between 120 and 240 min, followed by a period of 24
      h, when the rate of release remains approximately constant, approaching the zero
      order kinetics; the release rates for the polymers beads are as follows: pNIPAM
      C>pNIPAM-B>pNIPAM-A. The pattern of release rates at temperature over the VPTT is
      as follows: pNIPAM-C>pNIPAM-A>pNIPAM-B. In the presence of pNIPAM-C, the duration
      between the start of the release and the attained minimal inhibitory
      concentration (MIC) for most of the microbes, in conditions over the VPTT,
      increased from 60 to 90 min. The release prolongation could be ascribed to some
      interactions between the practically insoluble CX particle and the hydrophobic
      functional groups of the polymer.

PMID- 22629124
TI  - Acceleration of anaerobic cysteine transformations to sulfane sulfur consequent
      to gamma-glutamyl transpeptidase inhibition.
AB  - Toxicity of drugs and radiation in the cells is largely dependent on the level of
      thiols. In the present studies, an attempt has been made to inhibit gamma
      glutamyl transpeptidase (gammaGT) activity in EAT-bearing animals tissue. We have
      expected that administration of gammaGT inhibitors: acivicin and 1,2,3,4
      tetrahydroisoquinoline (TIQ) may influence GSH/gamma-glutamyl transpeptidase
      (gammaGT) system in the regulation of cysteine concentration and anaerobic
      cysteine metabolism in normal and cancer cells. Development of Ehrlich ascites
      tumor in mice enhances peroxidative processes, diminishes levels of nonprotein
      thiols (NPSH) and sulfane sulfur, and lowers activities of enzymes involved in
      its formation and transfer in the liver and kidney. Although gammaGT inhibitors
      further decrease NPSH level, they increase cysteine and sulfane sulfur levels.
      This means that upon gammaGT inhibition, cysteine can be efficiently acquired by
      normal liver and kidney cells via another pathway, that is so productive that
      sulfane sulfur level and intensity of anaerobic cysteine metabolism even rise.

PMID- 22629125
TI  - The use of recombinant pseudotype virus-like particles harbouring inserted target
      antigen to generate antibodies against cellular marker p16INK4A.
AB  - Protein engineering provides an opportunity to generate new immunogens with
      desired features. Previously, we have demonstrated that hamster polyomavirus
      major capsid protein VP1-derived virus-like particles (VLPs) are highly
      immunogenic and can be employed for the insertion of foreign epitopes at certain
      surface-exposed positions. In the current study, we have designed pseudotype VLPs
      consisting of an intact VP1 protein and VP2 protein fused with the target antigen
      -cellular marker p16(INK4A)--at its N terminus. Both proteins coexpressed in
      yeast were self-assembled to pseudotype VLPs harbouring the inserted antigen on
      the surface. The pseudotype VLPs were used for generation of antibodies against
      p16(INK4A) that represents a potential biomarker for cells transformed by high
      risk human papillomavirus (HPV). The pseudotype VLPs induced in immunized mice a
      strong immune response against the target antigen. The antisera raised against
      pseudotype VLPs showed specific immunostaining of p16(INK4A) protein in malignant
      cervical tissue. Spleen cells of the immunized mice were used to generate
      monoclonal antibodies against p16(INK4A) protein. The specificity of antibodies
      was proven by the immunostaining of HPV-transformed cells. In conclusion, the
      current study demonstrates the potential of pseudotype VLPs with inserted target
      antigen as a new type of immunogens to generate antibodies of high diagnostic
      value.

PMID- 22629126
TI  - Comparison of BTX profiles and their mutagenicity assessment at two sites of
      Agra, India.
AB  - In the present study, the concentrations of three volatile organic compounds
      (VOCs), namely, acronym for benzene, toluene, and xylenes (BTX) were assessed
      because of their role in the tropospheric chemistry. Two representative sites, a
      roadside and a petrol pump, were chosen for sample collection. VOCs were
      collected using SKC-activated charcoal tubes and SKC personal sampler and
      characterized by gas chromatograph using flame ionization detector. Among BTX,
      benzene had the highest concentration. At the roadside, mean concentration of
      benzene, toluene, o-,m-xylene, and p-xylene were 14.7 +/- 2.4 MUgm(-3), 8.1 +/-
      1.2 MUgm(-3), 2.1 +/- 0.8 MUgm(-3), and 5.1 +/- 1.2 MUgm(-3), respectively. At
      the petrol pump, the mean concentrations of benzene, toluene, o-,m-xylene and p
      xylene were 19.5 +/- 3.7 MUgm(-3), 12.9 +/- 1.1 MUgm(-3), 3.6 +/- 0.5 MUgm(-3)
      and 11.1 +/- 1.5 MUgm(-3), respectively, and were numerically higher by a
      fraction of 2. Monthly variation of BTX showed maximum concentration in winter.
      Inter-species ratios and inter-species correlation indicated traffic as the major
      source of BTX. Extracts of samples were positive in both Salmonella typhimurium
      tester strains TA98 and TA100 without metabolic activation suggesting the
      presence of direct mutagens in ambient air that can cause both frame-shift and
      base-pair mutation. The mutagenic response was greater for TA100 than TA98
      suggesting greater activity for base-pair mutagenicity than frame-shift
      mutagenicity and was found to be statistically significant.

PMID- 22629127
TI  - A histological study of ovarian development in the giant red shrimp
      Aristaeomorpha foliacea (Crustacea: Decapoda: Aristeidae) from the Southern
      Tyrrhenian Sea (Western Mediterranean).
AB  - The reproductive features of the giant red shrimp, Aristaeomorpha foliacea, were
      investigated in the southern Tyrrhenian sea by experimental trawl sampling. The
      annual length-frequency distribution showed a multimodal trend in females,
      ranging between 16 and 67 mm carapace length (CL), and a unimodal trend in males
      (18-45 mm CL). Mature males occurred in different proportions all year round,
      while females displayed seasonal maturity (June-September), with a peak in July.
      Six oocyte developmental stages were identified, the most advanced of which (Pv,
      postvitellogenic) had never been described before in this species. Ovary
      development followed a group-synchronous pattern, with the yolked oocyte stock
      clearly separated from the reservoir of unyolked oocytes, suggesting that A.
      foliacea is a total spawner, with determinate fecundity. Based upon histological
      findings, a revision of macroscopic maturity staging employed in Mediterranean
      bottom trawl surveys (MEDITS) is proposed.

PMID- 22629128
TI  - Antibiotic synergy interaction against multidrug-resistant Pseudomonas aeruginosa
      isolated from an abattoir effluent environment.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen in environmental waters with
      a high prevalence of multidrug resistance. In this study the synergistic efficacy
      of synergy antibiotic combinations in multidrug-resistant P. aeruginosa strains
      isolated from an abattoir effluent was investigated. Water samples were processed
      using membrane filtration; Pseudomonas was isolated with Pseudomonas Isolation
      Agar and confirmed using polymerase chain reaction with specie-specific primer.
      Susceptibility studies and in vitro synergy interaction testing were carried out,
      employing agar dilution and Etest procedure, respectively. Resistance was noted
      for clinically relevant antipseudomonal agents tested. Finding from antibiotic
      synergy interaction studies revealed that cefepime, imipenem, and meropenem
      combined with amikacin resulted in statistically significant (P < 0.0001) in
      vitro antibiotics synergy interaction, indicating the possible use of this
      regimen in treatment of pseudomonal infections.

PMID- 22629129
TI  - Psychomotor functions and interval timing in patients receiving intravenous
      anesthesia for endoscopic procedures: the pilot study.
AB  - Introduction. The aim of this study was to evaluate two measures in a cognitive
      examination: psychomotor function and the perception of time (PT) in patients
      after intravenous anesthesia for endoscopic procedures. Material and Methods. We
      tested 23 anesthetized patients (Anesthesia Group, AG) and 17 not anesthetized
      patients (Control Group, CG). The Dufour Cross-Shaped Apparatus (DA) was used to
      assess quick reactions. Perception of time (PT) was measured for 1-, 2-, 5-, and
      7-second intervals. The tests were performed before the anesthesia was
      administered and 1.5, 3, and 6 hours after the procedure was completed. Results.
      The intervals that were generated and the reproduced visual stimuli were shorter
      than the patterns. The reproduced 1- and 2-second auditory stimuli were longer
      than the patterns. The remaining reproduced auditory impulses were shorter than
      the patterns. Conclusions. In anesthetized patients, quick psychomotor reactions
      and the ability to time intervals are preserved 1.5 h and later after intravenous
      anesthesia for endoscopy.

PMID- 22629130
TI  - Changes in serum natriuretic peptide levels after percutaneous closure of small
      to moderate ventricular septal defects.
AB  - Background. B-type natriuretic peptide has been shown to be a very sensitive and
      specific marker of heart failure. In this study, we aimed to investigate the
      effect of percutaneous closure of ventricular septal defects with Amplatzer
      septal occluders on brain natriuretic peptide levels. Methods. Between 2008 and
      2011, 23 patients underwent successfully percutaneous ventricular septal defect
      closure in 4 cardiology centers. Brain natriuretic peptide levels were measured
      in nine patients (4 male, mean ages were 25.3 +/- 14.3) who underwent
      percutaneous closure with Amplatzer occluders for membranous or muscular
      ventricular septal defects were enrolled in the study. Brain natriuretic peptide
      levels were measured one day before and one month after the closure. Patients
      were evaluated clinically and by echocardiography one month after the procedure.
      Results. Percutaneous closures of ventricular septal defects were successfully
      performed in all patients. There was not any significant adverse event in
      patients group during followup. Decrease in brain natriuretic peptide levels
      after closure were statistically significant (97.3 +/- 78.6 versus 26.8 +/- 15.6,
      P = 0.013). Conclusion. Brain Natriuretic Peptide levels are elevated in patients
      with ventricular septal defects as compared to controls. Percutaneous closure of
      Ventricular Septal Defect with Amplatzer occluders decreases the BNP levels.

PMID- 22629131
TI  - Phytophthora capsici epidemic dispersion on commercial pepper fields in
      Aguascalientes, Mexico.
AB  - Chili pepper blight observed on pepper farms from north Aguascalientes was
      monitored for the presence of Phytophthora capsici during 2008-2010. Initially,
      ELISA tests were directed to plant samples from greenhouses and rustic nurseries,
      showing an 86% of positive samples. Later, samples of wilted plants from the
      farms during the first survey were tested with ELISA. The subsequent survey on
      soil samples included mycelia isolation and PCR amplification of a 560 bp
      fragment of ITS-specific DNA sequence of P. capsici. Data was analyzed according
      to four geographical areas defined by coordinates to ease the dispersal
      assessment. In general, one-third of the samples from surveyed fields contained
      P. capsici, inferring that this may be the pathogen responsible of the observed
      wilt. Nevertheless, only five sites from a total of 92 were consistently negative
      to P. capsici. The presence of this pathogen was detected through ELISA and
      confirmed through PCR. The other two-thirds of the negative samples may be
      attributable to Fusarium and Rhizoctonia, both isolated instead of Phytophthora
      in these areas. Due to these striking results, this information would be of
      interest for local plant protection committees and farmers to avoid further
      dispersal of pathogens to new lands.

PMID- 22629132
TI  - Effects of aflatoxin on some haematological parameters and protective
      effectiveness of esterified glucomannan in Merino rams.
AB  - The objective of the present study was to evaluate the toxic effects of aflatoxin
      on some hematological parameters and to determine the preventive effectiveness of
      added glucomannan. In the study, 32 Merino rams were used, and the rams were
      separated equally to four groups as control (C), glucomannan (G), glucomannan +
      aflatoxin (AG), and aflatoxin (A). Erythrocyte, leukocyte count, hemoglobin, and
      hematocrit levels were decreased in A group compared with the other groups, and
      there was a reduction in similar parameters in AG group compared to control
      values. On the other hand, these parameters were tended to increase in AG group
      compared to A group values. Aflatoxicosis caused the lymphocytopenia and
      monocytopenia but increased percentage of neutrophil counts. In conclusion, the
      results determined in the study might be important to demonstrate the effects of
      aflatoxicosis and glucomannan on some haematological parameters before the
      clinical symptoms appear.

PMID- 22629133
TI  - Perceiving numbers affects the internal random movements generator.
AB  - According to the evidence of direct relationships among space, numbers, and
      finger representations, a random movement generation (RMG) task was employed in
      order to investigate whether numerical exposure can influence the finger
      selection of healthy humans. To this purpose a group of participants were asked
      to generate random finger movements during the exposure to several numerical
      cues. Although participants were explicitly asked to move finger as random as
      possible, results showed that left-hand fingers were moved more frequently than
      right-hand fingers when low numerical cues (from 1 to 3) were presented, and,
      vice versa, right-hand fingers were moved more frequently than left-hand fingers
      when high numerical cues (ranged from 7 to 9) were presented. The current result
      suggests that spontaneous actions can be affected by abstract information,
      providing an evidence that numerical concepts can influence low-level, non-goal
      directed behaviours.

PMID- 22629134
TI  - A study of Epstein-Barr virus BRLF1 activity in a Drosophila model system.
AB  - Epstein-Barr virus, a member of the herpesvirus family, infects a large majority
      of the human population and is associated with several diseases, including
      cancer. We have created Drosophila model systems to study the interactions
      between host cellular proteins and the Epstein-Barr virus (EBV) immediate-early
      genes BRLF1 and BZLF1. BRLF1 and BZLF1 function as transcription factors for
      viral transcription and are also potent modifiers of host cell activity. Here we
      have used our model systems to identify host cell genes whose proteins modulate
      BRLF1 and BZLF1 functions. Via our GMR-R model system, we have found that BRLF1
      expression results in overproliferation of fly tissue, unlike BZLF1, and does so
      through the interaction with known tumor suppressor genes. Through an additional
      genetic screen, we have identified several Drosophila genes, with human homologs,
      that may offer further insights into the pathways that BRLF1 interacts with in
      order to promote EBV replication.

PMID- 22629135
TI  - Gender and age-dependent etiology of community-acquired urinary tract infections.
AB  - Urinary tract infections (UTIs) are among the most frequent community-acquired
      infections worldwide. Escherichia coli is the most common UTI pathogen although
      underlying host factors such as patients' age and gender may influence prevalence
      of causative agents. In this study, 61 273 consecutive urine samples received
      over a 22-month period from outpatients clinics of an urban area of north Italy
      underwent microbiological culture with subsequent bacterial identification and
      antimicrobial susceptibility testing of positive samples. A total of 13 820
      uropathogens were isolated and their prevalence analyzed according to patient's
      gender and age group. Overall Escherichia coli accounted for 67.6% of all
      isolates, followed by Klebsiella pneumoniae (8.8%), Enterococcus faecalis (6.3%),
      Proteus mirabilis (5.2%), and Pseudomonas aeruginosa (2.5%). Data stratification
      according to both age and gender showed E. coli isolation rates to be lower in
      both males aged >=60 years (52.2%), E. faecalis and P. aeruginosa being more
      prevalent in this group (11.6% and 7.8%, resp.), as well as in those aged <=14
      years (51.3%) in whom P. mirabilis prevalence was found to be as high as 21.2%.
      Streptococcus agalactiae overall prevalence was found to be 2.3% although it was
      shown to occur most frequently in women aged between 15 and 59 years (4.1%).
      Susceptibility of E. coli to oral antimicrobial agents was demonstrated to be as
      follows: fosfomycin (72.9%), trimethoprim/sulfamethoxazole (72.9%), ciprofloxacin
      (76.8%), ampicillin (48.0%), and amoxicillin/clavulanate (77.5%). In conclusion,
      both patients' age and gender are significant factors in determining UTIs
      etiology; they can increase accuracy in defining the causative uropathogen as
      well as providing useful guidance to empiric treatment.

PMID- 22629136
TI  - Socioeconomic importance of the banana tree (Musa spp.) in the Guinean Highland
      Savannah agroforests.
AB  - Home gardens are defined as less complex agroforests which look like and function
      as natural forest ecosystems but are integrated into agricultural management
      systems located around houses. Investigations were carried out in 187 households.
      The aim of the study was to identify the different types of banana home gardens
      existing in the periurban zone of Ngaoundere town. The results showed that the
      majority of home gardens in the area were very young (less than 15 years old) and
      very small in size (less than 1 ha). Eleven types of home gardens were found in
      the periurban area of Ngaoundere town. The different home garden types showed
      important variations in all their structural characteristics. Two local species
      of banana are cultivated in the systems, Musa sinensis and Musa paradisiaca. The
      total banana production is 3.57 tons per year. The total quantity of banana
      consumed in the periurban zone was 3.54 tons (93.5%) whereas 1.01 tons were sold
      in local or urban markets. The main banana producers belonged to home gardens 2,
      4, 7, and 9. The quantity of banana offered to relatives was more than what the
      farmers received from others. Farmers, rely on agroforests because the flow of
      their products helps them consolidate friendship and conserve biodiversity at the
      same time.

PMID- 22629137
TI  - Heavy metal accumulation and the genotoxicity in barbel (Barbus barbus) as
      indicators of the Danube river pollution.
AB  - The aim of this study was to analyze 16 trace elements (Al, As, B, Ba, Cd, Co,
      Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Sr, and Zn) in different barbel (Barbus barbus)
      tissues and to detect the presence of genotoxic effects in erythrocytes with the
      alkaline comet assay. Barbel specimens were collected in the Danube river near
      Belgrade, Serbia, where the discharge of untreated communal and industrial
      wastewaters is likely to produce negative effects on fish residing in this area.
      The highest concentrations of Sr, Mn, Fe, Ba, B, and Al were found in gills, Mo
      and Cu in liver, and As and Zn in gonads. Concentrations of Zn and Fe were above
      maximum acceptable concentrations (MACs) in a number of gonad, gill, and liver
      samples. Three-year-old barbel specimens had higher tail moment and Zn
      concentrations in gills (1.71 and 51.20 MUg/g dw, resp.) than 5-year-old
      specimens (0.85 and 42.51 MUg/g dw, resp.). Results indicate that the younger
      barbel specimens might be more suitable for the monitoring of environmental
      pollution.

PMID- 22629138
TI  - Bach adsorption study for the extraction of silver ions by hydrazone compounds
      from aqueous solution.
AB  - Sorbent materials based on a hydrazone Schiff base compound,
      C(14)H(11)BrN(4)O(4), were prepared either by immobilizing the ligand into sol
      gel (SG1) or bonding to silica (SG2). The sorbent materials were characterized by
      FT-IR, EDX, SEM, TEM, and TGA. The sorption characteristics of a matrix of eight
      transition metal ions (Ag(+), Cu(2+), Co(2+), Ni(2+), Fe(3+), Pb(2+), Zn(2+), and
      Mn(2+)) using batch method were studied. Several key parameters that affected the
      extraction efficiency such as pH, contact time, metal ions concentration, and gel
      size (for SGl) were investigated and optimized. Under the optimized conditions,
      the physically immobilized hydrazone sorbent (SG1) exhibits highest selectivity
      towards Ag(+) ions, while the chemically bonded hydrazone sorbent (SG2) exhibits
      high extraction for all metal ions tested. However, for practical applications
      such as the removal and preconcentration of Ag(+), the physically immobilized
      sorbent (SG1) is preferred.

PMID- 22629139
TI  - Triacylglycerols composition and volatile compounds of virgin olive oil from
      Chemlali cultivar: comparison among different planting densities.
AB  - The present study focused on the comparison the chemical composition of virgin
      olive oil samples obtained from fruits of the main Tunisian olive cultivar
      (Chemlali) grown in four planting densities (156, 100, 69, and 51 trees ha(-1)).
      Despite the variability in the triacylglycerols and volatile compounds
      composition, the quality indices (free fatty acids, peroxide value, and
      spectrophotometric indices K(232) and K(270)) all of the virgin olive oils
      samples studied met the commercial standards. Decanal was the major constituent,
      accounting for about 30% of the whole volatiles. Moreover, the chemical
      composition of the volatile fraction of the oil from fruits of trees grown at the
      planting density of 156, 100, and 51 trees ha(-1) was also characterised by the
      preeminence of 1-hexanol, while oils from fruits of trees grown at the planting
      density of 69 trees ha(-1) had higher content of (E)-2-hexenal (20.3%). Our
      results confirm that planting density is a crucial parameter that may influence
      the quality of olive oils.

PMID- 22629140
TI  - Prognostic value of hepatocyte growth factor, syndecan-1, and osteopontin in
      multiple myeloma and monoclonal gammopathy of undetermined significance.
AB  - Our aim was to compare serum levels of selected biological parameters in
      different phases of multiple myeloma (MM) and monoclonal gammopathy of
      undetermined significance (MGUS) to determine their diagnostic and prognostic
      potential. A cohort of 234 individuals was assessed for serum levels of
      hepatocyte growth factor (HGF), syndecan-1/CD(138) (SYN), and osteopontin (OPN).
      The patients with MM (N = 156) were divided into 3 groups: at the time of
      diagnosis (N = 45), in relapse/progression (N = 56), and in remission (N = 50).
      The analysis revealed significant differences of all three parameters in
      comparison of active and remission phase MM. Moreover, the parameters in active
      myeloma were significantly higher than in MGUS. Within the comparison of active
      disease (newly diagnosed and relapsing), there was no significant difference.
      Similar results were in remission phase MM and MGUS. There was no relationship of
      pretreatment levels of the parameters to therapeutic response. We conclude that
      serum levels of HGF, OPN, and SYN correspond to the activity of MM and might
      become useful in differentiation of MGUS, asymptomatic MM, and overt/symptomatic
      form of MM. The levels of all three parameters behave accordingly with MM
      activity. Pretreatment measurement without the assessment of their kinetics,
      however, has no relationship to therapeutic response.

PMID- 22629141
TI  - Back to natural fiber: wool color influences its sensitivity to enzymatic
      treatment.
AB  - There are many missed biotechnological opportunities in the developmental
      countries. Wool quality improvement is one of them. This study is concerning with
      improving the wool quality using technical enzymes. White wool proves to be more
      susceptible to the enzymatic treatment than blackish brown wool. This proves that
      the enzymatic reaction is sensitive to the natural color differences between wool
      fibers. A simple enzymatic method has been used to improve the wool quality as
      well as to investigate the changes happened in the wool fibers. Geobacillus
      stearothermophilus has been used under mesophilic and static cultivation
      conditions using wool as the main carbon source. These conditions prove to be
      more suitable for maintaining the fiber structure, less expensive, and reliable
      as an in-house biotechnological process that can be adapted everywhere. The
      enzyme activity in case of white wool was 4 Units/ml and for blackish brown wool
      was 1.5 Units/ml. Electron microscope has been used to evaluate the end result.
      By following the process included in this paper using probable microbial
      strain(s), the wool quality improvement can be applied globally and can add
      another value to the economy of the developmental countries.

PMID- 22629142
TI  - Applying fuzzy logic to comparative distribution modelling: a case study with two
      sympatric amphibians.
AB  - We modelled the distributions of two toads (Bufo bufo and Epidalea calamita) in
      the Iberian Peninsula using the favourability function, which makes predictions
      directly comparable for different species and allows fuzzy logic operations to
      relate different models. The fuzzy intersection between individual models,
      representing favourability for the presence of both species simultaneously, was
      compared with another favourability model built on the presences shared by both
      species. The fuzzy union between individual models, representing favourability
      for the presence of any of the two species, was compared with another
      favourability model based on the presences of either or both of them. The fuzzy
      intersections between favourability for each species and the complementary of
      favourability for the other (corresponding to the logical operation "A and not
      B") were compared with models of exclusive presence of one species versus the
      exclusive presence of the other. The results of modelling combined species data
      were highly similar to those of fuzzy logic operations between individual models,
      proving fuzzy logic and the favourability function valuable for comparative
      distribution modelling. We highlight several advantages of fuzzy logic over other
      forms of combining distribution models, including the possibility to combine
      multiple species models for management and conservation planning.

PMID- 22629143
TI  - Influence of drought and sowing time on protein composition, antinutrients, and
      mineral contents of wheat.
AB  - The present study in a two-year experiment investigated the influence of drought
      and sowing time on protein composition, antinutrients, and mineral contents of
      wheat whole meal of two genotypes differing in their water requirements.
      Different thermal conditions prevailing during the grain filling period under
      different sowing time generated a large effect on the amount of total soluble
      proteins. Late sown conditions offered higher protein content accompanied by
      increased albumin-globulin but decreased glutenin content. Fe content was
      increased to 20-23%; however, tannin decreased to 18-35% under early sown rain
      fed conditions as compared to irrigated timely sown conditions in both the
      genotypes. Activity of trypsin inhibitor was decreased under rain-fed conditions
      in both genotypes. This study inferred that variable sowing times and irrigation
      practices can be used for inducing variation in different wheat whole meal
      quality characteristics. Lower temperature prevailing under early sown rain-fed
      conditions; resulted in higher protein content. Higher Fe and lower tannin
      contents were reported under early sown rain-fed conditions however, late sown
      conditions offered an increase in phytic acid accompanied by decreased
      micronutrients and glutenin contents.

PMID- 22629144
TI  - Diet-induced swine model with obesity/leptin resistance for the study of
      metabolic syndrome and type 2 diabetes.
AB  - The objective of the present study was to determine the suitability of a swine
      breed with leptin resistance and predisposition to obesity (the Iberian pig) as
      model for studies on metabolic syndrome and type 2 diabetes. Thus, six Iberian
      sows had ad libitum access to food enriched with saturated fat (SFAD group; food
      consumption was estimated to be 4.5 kg/animal/day) whilst four females acted as
      controls and were fed with 2 kg/animal/day of a commercial maintenance diet.
      After three months of differential feeding, SFAD animals developed central
      obesity, dyslipidemia, insulin resistance and impaired glucose tolerance, and
      elevated blood pressure; the five parameters associated with the metabolic
      syndrome. Thus, the current study characterizes the Iberian pig as a robust,
      amenable, and reliable translational model for studies on nutrition-associated
      diseases.

PMID- 22629145
TI  - Transformation of synthetic allicin: the influence of ultrasound, microwaves,
      different solvents and temperatures, and the products isolation.
AB  - The transformation of the synthesized allicin, using conventional method, the
      influence of ultrasound and microwaves, in different organic solvents
      (acetonitrile, acetone, methanol, and chloroform), at various temperatures (room
      temperature, 45  degrees C, and 55  degrees C) was investigated. Allicin
      degradation kinetic was monitored by HPLC. Allicin transformation under the
      effect of microwaves is faster than transformations performed under the influence
      of ultrasound or by conventional method. Increase of the temperature accelerates
      allicin transformation. Pharmacologically active compounds of (E)-ajoene, (Z)
      ajoene, 3-vinyl-4H-1,2-dithiin, 2-vinyl-4H-1,3-dithiin, and diallyl disulfide
      were isolated from the mixture of transformation products of allicin under the
      influence of microwaves in methanol at 55  degrees C, which is according to
      kinetic parameters (highest values of the order of reaction and the lowest
      activation energy) the optimal method.

PMID- 22629147
TI  - Biochemical aspects of a serine protease from Caesalpinia echinata Lam.
      (Brazilwood) seeds: a potential tool to access the mobilization of seed storage
      proteins.
AB  - Several proteins have been isolated from seeds of leguminous, but this is the
      first report that a protease was obtained from seeds of Caesalpinia echinata
      Lam., a tree belonging to the Fabaceae family. This enzyme was purified to
      homogeneity by hydrophobic interaction and anion exchange chromatographies and
      gel filtration. This 61-kDa serine protease (CeSP) hydrolyses H-D-prolyl-L
      phenylalanyl-L-arginine-p-nitroanilide (K(m) 55.7 MUM) in an optimum pH of 7.1,
      and this activity is effectively retained until 50  degrees C. CeSP remained
      stable in the presence of kosmotropic anions (PO(4) (3-), SO(4) (2-), and
      CH(3)COO(-)) or chaotropic cations (K(+) and Na(+)). It is strongly inhibited by
      TLCK, a serine protease inhibitor, but not by E-64, EDTA or pepstatin A. The
      characteristics of the purified enzyme allowed us to classify it as a serine
      protease. The role of CeSP in the seeds cannot be assigned yet but is possible to
      infer that it is involved in the mobilization of seed storage proteins.

PMID- 22629146
TI  - Using visual aids to improve communication of risks about health: a review.
AB  - Recent research has shown that patients frequently experience difficulties
      understanding health-relevant numerical concepts. A prominent example is
      denominator neglect, or the tendency to pay too much attention to numerators in
      ratios (e.g., number of treated patients who died) with insufficient attention to
      denominators (e.g., overall number of treated patients). Denominator neglect can
      lead to inaccurate assessments of treatment risk reduction and thus can have
      important consequences for decisions about health. Here, we reviewed a series of
      studies investigating (1) different factors that can influence patients'
      susceptibility to denominator neglect in medical decision making--including
      numerical or language-related abilities; (2) the extent to which denominator
      neglect can be attenuated by using visual aids; and (3) a factor that moderates
      the effectiveness of such aids (i.e., graph literacy). The review spans
      probabilistic national U.S. and German samples, as well as immigrant (i.e.,
      Polish people living in the United Kingdom) and undergraduate samples in Spain.
      Theoretical and prescriptive implications are discussed.

PMID- 22629148
TI  - Simultaneous determination of cyclosporine A, tacrolimus, sirolimus, and
      everolimus in whole-blood samples by LC-MS/MS.
AB  - OBJECTIVES: Cyclosporine A (CyA), tacrolimus (TRL), sirolimus (SIR), and
      everolimus (RAD) are immunosuppressive drugs frequently used in organ
      transplantation. Our aim was to confirm a robust sensitive and selective liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of
      CyA, TRL, SIR, and RAD in whole-blood samples. MATERIALS AND METHODS: We used an
      integrated online solid-phase extraction-LC-MS/MS system and atmospheric pressure
      ionization tandem mass spectrometry (API-MS/MS) in the multiple reaction
      monitoring (MRM) detection mode. CyA, TRL, SIR, and RAD were simultaneously
      analyzed in whole blood treated with precipitation reagent taken from transplant
      patients. RESULTS: System performance parameters were suitable for using this
      method as a high-throughput technique in clinical practice. The high
      concentration of one analyte in the sample did not affect the concentration of
      other analytes. Total analytical time was 2.5 min, and retention times of all
      analytes were shorter than 2 minutes. CONCLUSION: This LC-MS/MS method can be
      preferable for therapeutic drug monitoring of these immunosuppressive drugs (CyA,
      TRL, SRL, and RAD) in whole blood. Sample preparation was too short and simple in
      this method, and it permits robust, rapid, sensitive, selective, and simultaneous
      determination of these drugs.

PMID- 22629150
TI  - Climatological aspects of aerosol physical characteristics in Tunisia deduced
      from sun photometric measurements.
AB  - Atmospheric and climatic data measured at Thala site (Tunisia) for a long-time
      period (1977-2001) are used to analyse the monthly, seasonal, and annual
      variations of the aerosol optical depth at 1 MUm wavelength. We have shown that
      aerosol and microphysical properties and the dominating aerosol types depend on
      seasons. A comparison of the seasonal cycle of aerosol optical characteristics at
      Thala site showed that the contribution of long-range transported particles is
      expected to be larger in summer as a consequence of the weather stability typical
      of this season. Also, the winter decrease in atmospheric turbidity may result
      from increases in relative humidity and decreases in temperature, leading to
      increased particle size and mass and increased fall and deposition velocities.
      The spring and autumn weather patterns usually carry fine dust and sand particles
      for the desert area to Thala region. The annual behaviour of the aerosol optical
      depth recorded a period of stead increase started in 1986 until 2001. Trends in
      atmospheric turbidity after 1988 could be explained other ways by the
      contribution of the eruption of Mount Pinatubo in 1991 and by local or regional
      changes in climate or in aerosol emissions.

PMID- 22629149
TI  - Renewed avenues through exercise muscle contractility and inflammatory status.
AB  - Physical inactivity leads to the accumulation of visceral fat and, consequently,
      to the activation of a network of inflammatory pathways which may promote
      development of insulin resistance, atherosclerosis, neurodegeneration, and tumour
      growth. These conditions belong to the "diseasome of physical inactivity". In
      contrast, the protective effect of regular exercise against diseases associated
      with chronic inflammation may to some extent be ascribed to an anti-inflammatory
      effect. The so called "acute exercise threshold", the complex mixture of several
      variables involved in exercise, such as type, volume, frequency, and intensity
      range is capable of inducing positive physiological adaptations and has been
      specifically addressed in the recent literature. The major concern is related to
      the level of the threshold: "exercise training shifts from a therapeutic adaptive
      intervention to one with potential pathological consequences". Nonetheless, if
      the mechanical stimulus is too weak to disrupt cellular homeostasis, training
      adaptations will not occur. Answering these questions could present practical
      applications, especially during inflammatory diseases associated with detrimental
      muscle effects and could theoretically constitute a "new" therapeutic approach to
      treat/improve an inflammatory state. This paper aims to describe specific data
      from the literature regarding the effects of exercise on inflammatory diseases in
      order to promote a more sophisticated perspective on the anti-inflammatory
      effects of exercise.

PMID- 22629151
TI  - Assessing the risk of birth defects associated with exposure to fixed-dose
      combined antituberculous agents during pregnancy in rats.
AB  - Due to the risks of disease progression and transmission to the newborn,
      treatment of tuberculosis is often pursued during pregnancy and fixed-dose
      combined antituberculous agents have been found to be beneficial. Unfortunately,
      there is paucity of data on the safety of the fixed-dose combined antituberculous
      drugs during pregnancy. This study intends to assess the teratogenic effect of
      fixed-dose combined antituberculous drugs on the organogenesis stage of fetal
      development and also investigate the possible roles of vitamin C in modulating
      the teratogenic effects of these agents on the fetus using animal model. Pregnant
      rats were divided into 3 groups with 12 animals per group: group 1 received
      distilled water (10 mL/kg) orally; group 2 received 51.4 mg/kg/day of fixed-dose
      combined antituberculous agents orally; group 3 received 51.4 mg/kg/day of fixed
      dose combined antituberculous agents plus vitamin C (10 mg/kg/day) orally. Six
      rats in each group were randomly selected and sacrificed on day 20 by cervical
      dislocation prior to day 21 of gestation, and the foetuses were harvested through
      abdominal incision for physical examination. Blood samples were collected from
      the 1st filial rats of the remaining six animals for biochemical and
      hematological examination. The liver, kidney, heart, and brain of all the
      sacrificed animals were used for histopathological examination. There were
      significant (P <= 0.05) low birth weights of the foetuses of the animals that
      were treated with fixed-dose combined antituberculous agents. The haematological
      parameters also revealed a reduction in the platelets counts and neutrophiles at
      the first filial generation. Significant (P <= 0.05) elevations in the levels of
      aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the foetuses
      of the animals treated with fixed-dose combined antituberculous agents were also
      observed. However, the combination of vitamin C with fixed-dose combined
      antituberculous agents significantly (P <= 0.05) reduced the level of AST. Fixed
      dose combined antituberculous agents have teratogenic potential as shown in low
      birth weight and mild liver damage in the first filial of the treated animals. As
      much as it is imminent to treat TB patients in pregnancy, there is need to always
      exercise caution and clinically weigh the risk-benefit ratio.

PMID- 22629153
TI  - Moral competence as a positive youth development construct: a conceptual review.
AB  - Moral competence refers to the affective orientation to perform altruistic
      behaviors and the ability to judge moral issues logically. A five-stage theory of
      moral development is proposed. Both western and Chinese perspectives are
      incorporated in the elaboration of the characteristics of each stage. A brief
      review of the antecedents of moral competence is presented. The relationship
      between moral competence and adolescent developmental outcomes is also discussed.
      Some practical ways to promote moral competence are suggested. School-based
      programs may be effective in the promotion of moral competence provided it is
      based on all-round or whole-person development and the length of the program
      should be sufficiently long.

PMID- 22629152
TI  - Demineralization of enamel in primary second molars related to properties of the
      enamel.
AB  - Enamel structure is of importance in demineralization. Differences in porosity in
      enamel effect the rate of demineralization, seen between permanent and deciduous
      teeth. Individual differences have been shown in the mean mineral concentration
      values in enamel, the role of this in demineralization is not thoroughly
      investigated. The aim of this study was to study variations of depths of
      artificial lesions of demineralization and to analyze the depth in relation to
      variations in the chemical and mineral composition of the enamel. A demineralized
      lesion was created in second primary molars from 18 individuals. Depths of
      lesions were then related to individual chemical content of the enamel. Enamel
      responded to demineralization with different lesion depths and this was
      correlated to the chemical composition. The carbon content in sound enamel was
      shown to be higher where lesions developed deeper. The lesion was deeper when the
      degree of porosity of the enamel was higher.

PMID- 22629154
TI  - Spatiotemporal distribution of harmful algal flora in the tropical estuarine
      complex of Goa, India.
AB  - Mandovi and Zuari estuarine complex is monsoon-influenced estuaries located along
      the central west coast of India. During the past few years, there has been an
      increase in nutrient loading specially during monsoonal runoff which is
      responsible for the growth of harmful algal flora. To understand occurrence and
      distribution of harmful algal blooms species, daily/alternate day samplings were
      carried out in Mandovi and Zuari estuaries during 2007-2008 and 2008-2009
      periods, respectively, comprising of monsoon (June-November) and nonmonsoon
      (December-May). In Mandovi, total 54 HAB species with 49 in monsoon and 36 during
      nonmonsoon period were reported. In Zuari, total 46 HAB species with 38 in
      monsoon and 41 were reported during nonmonsoon period. Bray-Curtis cluster
      analysis based on log-transformed phytoplankton density detected seven well
      defined groups revealing spatiotemporal variability. The density of the dominant
      harmful algal species was significantly positively correlated with nutrients, but
      negatively correlated with salinity. The results of the study indicate that
      monsoon plays an important role in occurrence and distribution of harmful algal
      species having direct correlation with salinity variations and nutrient loading.

PMID- 22629155
TI  - Effect of calcium soap of fatty acids supplementation on serum biochemical
      parameters and ovarian activity during out-of-the-breeding season in crossbred
      ewes.
AB  - This experiment aimed to evaluate the effect of calcium soap of fatty acid (CSFA)
      supplementation on serum biochemical and hormones and ovarian activity during out
      of-the-breeding season in ewes. Twelve crossbred ewes, 2-3 years of age and
      weighting 45-55 kg, were allocated into two equal groups. The first group was
      control and the other was treated with 50 g/head of CSFA. All ewes were fed basal
      diet and treated with 60 mg of medroxy progesterone acetate intravaginal sponge
      for 12 day. At the third day of sponge removal, the CSFA-treated group was given
      50 g/head of CSFA daily for two estrous cycles. During the estrus phase, ovarian
      activity was detected using ultrasonography in both groups. All ewes were then
      subjected to natural breeding and conception rate. Blood samples were collected
      from all ewes during treatment period. Results revealed significant (P < 0.05)
      increases in serum cholesterol, triglycerides, low-density lipoprotein
      cholesterol, glucose, and progesterone levels with decrease in calcium and
      phosphorous levels in treated group. In treated group, normal-size ovaries and
      more than one follicle on the ovaries were detected and pregnancy rate increased.
      In conclusion, CSFA supplementation was effective to maintain the reproductive
      performance when ewes were out of the breeding season.

PMID- 22629156
TI  - Lethal effects of Aspergillus niger against mosquitoes vector of filaria,
      malaria, and dengue: a liquid mycoadulticide.
AB  - Aspergillus niger is a fungus of the genus Aspergillus. It has caused a disease
      called black mold on certain fruits and vegetables. The culture filtrates
      released from the A. niger ATCC 66566 were grown in Czapek dox broth (CDB) then
      filtered with flash chromatograph and were used for the bioassay after a growth
      of thirty days. The result demonstrated these mortalities with LC(50), LC(90),
      and LC(99) values of Culex quinquefasciatus 0.76, 3.06, and 4.75, Anopheles
      stephensi 1.43, 3.2, and 3.86, and Aedes aegypti 1.43, 2.2, and 4.1 MUl/cm(2),
      after exposure of seven hours. We have calculated significant LT(90) values of
      Cx. quinquefasciatus 4.5, An. stephensi 3.54, and Ae. aegypti 6.0 hrs,
      respectively. This liquid spray of fungal culture isolate of A. niger can reduce
      malaria, dengue, and filarial transmission. These results significantly support
      broadening the current vector control paradigm beyond chemical adulticides.

PMID- 22629157
TI  - Enhanced removal of lead by chemically and biologically treated carbonaceous
      materials.
AB  - Hybrid sorbents and biosorbents were synthesized via chemical and biological
      treatment of active carbon by simple and direct redox reaction followed by
      surface loading of baker's yeast. Surface functionality and morphology of
      chemically and biologically modified sorbents and biosorbents were studied by
      Fourier Transform Infrared analysis and scanning electron microscope imaging.
      Hybrid carbonaceous sorbents and biosorbents were characterized by excellent
      efficiency and superiority toward lead(II) sorption compared to blank active
      carbon providing a maximum sorption capacity of lead(II) ion as 500 MUmol g(-1).
      Sorption processes of lead(II) by these hybrid materials were investigated under
      the influence of several controlling parameters such as pH, contact time, mass of
      sorbent and biosorbent, lead(II) concentration, and foreign ions. Lead(II)
      sorption mechanisms were found to obey the Langmuir and BET isotherm models. The
      potential applications of chemically and biologically modified-active
      carbonaceous materials for removal and extraction of lead from real water
      matrices were also studied via a double-stage microcolumn technique. The results
      of this study were found to denote to superior recovery values of lead (95.0-99.0
      +/- 3.0-5.0%) by various carbonaceous-modified-bakers yeast biosorbents.

PMID- 22629158
TI  - Factors associated with road accidents among Brazilian motorcycle couriers.
AB  - The objective of the study was to identify factors associated with reports of
      road accidents, among motorcycle couriers in two medium-sized municipalities in
      southern Brazil. A self-administered questionnaire was answered by motorcycle
      couriers that had worked for at least 12 months in this profession. The outcomes
      analyzed were reports on accidents and serious accidents over the 12 months prior
      to the survey. Bivariate and multivariate analyses by means of logistic
      regression were carried out to investigate factors that were independently
      associated with the outcomes. Seven hundred and fifty motorcycle couriers, of
      mean age 29.5 years (standard deviation = 8.1 ), were included in the study.
      Young age (18 to 24 years compared to >= 25 years, odds ratio [OR] = 1.77)
      speeding (OR = 1.48), and use of cell phones while driving (OR = 1.43) were
      factors independently associated with reports of accidents. For serious
      accidents, there was an association with alternation of work shifts (OR = 1.91)
      and speeding (OR = 1.67). The characteristics associated with accidents-personal
      (young age), behavioral (use of cell phones while driving and speeding), and
      professional (speeding and alternation of work shifts)-reveal the need to adopt
      wide-ranging strategies to reduce these accidents, including better work
      conditions for these motorcyclists.

PMID- 22629159
TI  - Are fish and standardized FETAX assays protective enough for amphibians? A case
      study on Xenopus laevis larvae assay with biologically active substances present
      in livestock wastes.
AB  - Biologically active substances could reach the aquatic compartment when livestock
      wastes are considered for recycling. Recently, the standardized FETAX assay has
      been questioned, and some researchers have considered that the risk assessment
      performed on fish could not be protective enough to cover amphibians. In the
      present study a Xenopus laevis acute assay was developed in order to compare the
      sensitivity of larvae relative to fish or FETAX assays; veterinary medicines
      (ivermectin, oxytetracycline, tetracycline, sulfamethoxazole, and trimethoprim)
      and essential metals (zinc, copper, manganese, and selenium) that may be found in
      livestock wastes were used for the larvae exposure. Lethal (LC(50)) and sublethal
      effects were estimated. Available data in both, fish and FETAX studies, were in
      general more protective than values found out in the current study, but not in
      all cases. Moreover, the presence of nonlethal effects, caused by ivermectin,
      zinc, and copper, suggested that several physiological mechanisms could be
      affected. Thus, this kind of effects should be deeply investigated. The results
      obtained in the present study could expand the information about micropollutants
      from livestock wastes on amphibians.

PMID- 22629160
TI  - Maternal and cord serum cytokine changes with continuous and intermittent labor
      epidural analgesia: a randomized study.
AB  - BACKGROUND: Maternal fever during labor epidural analgesia (LEA) may cause
      increased maternal and cord serum inflammatory cytokines. We report the effects
      of intermittent and continuous LEA on these cytokines. METHODS: Ninety-two women
      were randomly assigned to continuous (CLEA) or intermittent (ILEA) groups, 46 in
      each. Maternal temperature was checked and blood drawn at epidural insertion
      (baseline) and four-hourly until 4 h postpartum (4 PP). Cord blood was drawn
      after placental delivery. Interleukin-1beta (IL-1beta), interleukin-6 (IL-6),
      interleukin-8 (IL-8), granulocyte macrophage-colony stimulating factor (GM-CSF),
      and tumor necrosis factor-alpha (TNF-alpha) were measured and analyzed according
      to group randomization, and then combined and reanalyzed as febrile (temperature
      >= 38  degrees C) or afebrile groups. RESULTS: Significant intragroup changes
      from baseline were noted in some groups. Data are pg/mL, median (Q1/Q3). IL-6
      rose at all time points in all groups. CLEA: baseline: 18.5 (12.5/31.1), 4 h:
      80.0 (46.3/110.8), 8 h: 171.9 (145.3/234.3), and 4 PP: 81 (55.7/137.4). ILEA:
      baseline: 15.7 (10.2/27.1), 4 h: 68.2 (33.3/95.0), 8 h: 125.0 (86.3/195.0), and 4
      PP: 70.2 (54.8/103.6). Febrile group: baseline: 21.6 (13.8/40.9), 4 h: 83.9
      (47.5/120.8), 8 h: 186.7 (149.6/349.9), and 4 PP: 105.8 (65.7/158.8). Afebrile
      group: baseline: 10.9 (2.1/17.4), 4 h: 38.2 (15.0/68.2), 8 h: 93.8 (57.1/135.7),
      and 4 PP: 52.9 (25.1/78). IL-8 rose at all time points in CLEA: baseline: 2.68
      (0.0/4.3), 4 h: 3.7 (0.0/6.5), 8 h: 6.0 (3.3/9.6), 4 PP: 5.6 (0.8/8.0), and
      afebrile group baseline: 2.5 (0.0/4.7), 4 h: 3.3 (0.0/6.2), 8 h: 5.3 (1.9/9.8),
      and 4 PP: 4.7 (0.0/7.6). It fell at 4 PP in febrile group: baseline: 4.1
      (0.0/6.4), 4 h: 3.8 (0.0/6.5), 8 h: 5.2 (2.5/8.0), and 4 PP: 2.9 (0.0/4.0). GM
      CSF increased at 8 h and decreased at 4 PP in ILEA baseline: 2.73 (0.0/7.2), 4 h:
      2.73 (0.0/7.9), 8 h: 3.9 (2.7/11.5), and 4 PP: 2.0 (0.0/7.2). It increased at 4 h
      and 8 h and decreased at 4 PP in febrile group: baseline: 2.6 (0.0/4.2), 4 h: 3.2
      (2.1/7.0), 8 h: 4.0 (3.2/12.3), and 4 PP: 2.4 (1.7/12.6). There were no
      intergroup cytokine changes in maternal or cord serum in CLEA versus ILEA or
      febrile versus afebrile groups. CONCLUSIONS: Some cytokines, especially IL-6,
      rise physiologically during labor epidural analgesia.

PMID- 22629161
TI  - Ultraviolet-B radiation and nitrogen affect nutrient concentrations and the
      amount of nutrients acquired by above-ground organs of maize.
AB  - UV-B radiation effects on nutrient concentrations in above-ground organs of maize
      were investigated at silking and maturity at different levels of applied nitrogen
      under field conditions. The experiment simulated a 20% stratospheric ozone
      depletion over Portugal. At silking, UV-B increased N, K, Ca, and Zn
      concentrations, whereas at maturity Ca, Mg, Zn, and Cu increased and N, P and Mn
      decreased in some plant organs. Generally, at maturity, N, Ca, Cu, and Mn were
      lower, while P, K, and Zn concentrations in stems and nitrogen-use efficiency
      (NUE) were higher in N-starved plants. UV-B and N effects on shoot dry biomass
      were more pronounced than on nutrient concentrations. Nutrient uptake decreased
      under high UV-B and increased with increasing N application, mainly at maturity
      harvest. Significant interactions UV-B x N were observed for NUE and for
      concentration and mass of some elements. For instance, under enhanced UV-B, N,
      Cu, Zn, and Mn concentrations decreased in leaves, except on N-stressed plants,
      whereas they were less affected by N nutrition. In order to minimize nutritional,
      economical, and environmental negative consequences, fertiliser recommendations
      based on element concentration or yield goals may need to be adjusted.

PMID- 22629162
TI  - Localisation of abundant and organ-specific genes expressed in Rosa hybrida
      leaves and flower buds by direct in situ RT-PCR.
AB  - In situ PCR is a technique that allows specific nucleic acid sequences to be
      detected in individual cells and tissues. In situ PCR and IS-RT-PCR are elegant
      techniques that can increase both sensitivity and throughput, but they are, at
      best, only semiquantitative; therefore, it is desirable first to ascertain the
      expression pattern by conventional means to establish the suitable conditions for
      each probe. In plants, in situ RT-PCR is widely used in the expression
      localisation of specific genes, including MADS-box and other function-specific
      genes or housekeeping genes in floral buds and other organs. This method is
      especially useful in small organs or during early developmental stages when the
      separation of particular parts is impossible. In this paper, we compared three
      different labelling and immunodetection methods by using in situ RT-PCR in Rosa
      hybrida flower buds and leaves. As target genes, we used the abundant beta-actin
      and RhFUL gene, which is expressed only in the leaves and petals/sepals of flower
      buds. We used digoxygenin-11-dUTP, biotin-11-dUTP, and fluorescein-12-dUTP
      labelled nucleotides and antidig-AP/ streptavidin-fluorescein-labelled
      antibodies. All of the used methods gave strong, specific signal and all of them
      may be used in localization of gene expression on tissue level in rose organs.

PMID- 22629163
TI  - Surgical treatment of patients with Lennox-Gastaut syndrome phenotype.
AB  - Lennox-Gastaut syndrome (LGS) is a devastating and refractory generalized
      epilepsy affecting children and adolescents. In this study we report the results
      of resective surgery in 18 patients with LGS phenotype who underwent single
      lobe/lesionectomy or multilobe resection plus multiple subpial transection and/or
      callosotomy. After surgery, seven patients became completely seizure-free (Engel
      Class I) and five almost seizure-free (Engel Class II). Additional four had
      significant seizure control (Engel Class III), and two had no change in seizure
      frequency (Engel Class IV). Of the 4 patients without any lesion on brain MRI, 2
      ended with Engel Class II, 1 with III and the other with IV in Engels'
      classification. Mean intelligence quotient (IQ) increased from 56.1 +/- 8.1 (mean
      +/- SD) before operation to 67.4 +/- 8.2 (mean +/- SD) after operation, a
      significant improvement (P = 0.001). Results also indicated that the younger the
      patient at surgery, or the shorter the interval between onset of seizure and
      resective operation, the better the intellectual outcome. Our data suggest that
      resective epilepsy surgery can be successful in patients with LGS phenotype as
      long as the EEG shows dominance of discharges in one hemisphere and corresponding
      ipsilateral imaging findings, even with contralateral ictal discharges.

PMID- 22629164
TI  - Trends and social differences in alcohol consumption during the postcommunist
      transition in Lithuania.
AB  - The aim of the study was to evaluate the trends and social differences in
      consumption of various types of alcoholic beverages in Lithuania over the
      postcommunist transition period (1994-2010). The data were obtained from nine
      nationally representative postal surveys of Lithuanian population aged 20-64
      conducted every second year (n = 17154). Prevalence of regular (at least once a
      week) consumption of beer, wine, or strong alcoholic beverages and the amount of
      alcohol consumed per week were examined. Regular beer drinking as well as the
      amounts consumed increased considerably in both genders. The increase in regular
      consumption of strong alcohol was found among women. Sociodemographic patterning
      of regular alcohol drinking was more evident in women than in men. In women,
      young age and high education were associated with frequent regular drinking of
      wine and beer. Social differences in regular alcohol drinking should be
      considered in further development of national alcohol control policy in
      Lithuania.

PMID- 22629165
TI  - The effects of subchronic exposure to terbuthylazine on early developmental
      stages of common carp.
AB  - The aim of this study was to assess the impact of terbuthylazine in surface
      waters on fish under experimental conditions. Subchronic toxic effects on embryos
      and larvae of common carp (Cyprinus carpio) were investigated during a 30-day
      toxicity test. The exposure to terbuthylazin showed no effect on mortality, but
      significant differences (P < 0.0001) were revealed on weight and growth
      parameters at concentrations of 520 and 820 MUg/L. The inhibition of specific
      growth rate at concentrations of 520 and 820 MUg/L was 14% compared to the
      control group. No significant negative effects on total body length and body
      weight were observed at lower concentrations (0.9 and 160 MUg/L). The
      concentrations 520 and 820 MUg/L were associated with a delay in development
      compared to other experimental groups and controls. On the basis of weight and
      growth rate evaluation and determination of developmental stages, the No Observed
      Effect Concentration (NOEC) of terbuthylazine was estimated at 160 MUg/L and the
      Lowest Observed Effect Concentration (LOEC) was 520 MUg/L. According to these
      results, the reported environmental concentration of terbuthylazine in Czech
      rivers does not impact growth, development, morphology, or histology of carp
      embryos and larvae.

PMID- 22629166
TI  - Analysis of the volumes of the posterior cranial fossa, cerebellum, and herniated
      tonsils using the stereological methods in patients with Chiari type I
      malformation.
AB  - OBJECTIVE: The aim of this study was to determine the posterior cranial fossa
      volume, cerebellar volume, and herniated tonsillar volume in patients with chiari
      type I malformation and control subjects using stereological methods. MATERIAL
      AND METHODS: These volumes were estimated retrospectively using the Cavalieri
      principle as a point-counting technique. We used magnetic resonance images taken
      from 25 control subjects and 30 patients with chiari type I malformation.
      RESULTS: The posterior cranial fossa volume in patients with chiari type I
      malformation was significantly smaller than the volume in the control subjects (P
      < 0.05). In the chiari type I malformation group, the cerebellar volume was
      smaller than the control group, but this difference was not statistically
      significant (P > 0.05). In the chiari type I malformation group, the ratio of
      cerebellar volume to posterior cranial fossa volume was higher than in the
      control group. We also found a positive correlation between the posterior cranial
      fossa volume and cerebellar volume for each of the groups (r = 0.865, P < 0.001).
      The mean (+/-SD) herniated tonsillar volume and length were 0.89 +/- 0.50 cm(3)
      and 9.63 +/- 3.37 mm in the chiari type I malformation group, respectively.
      Conclusion. This study has shown that posterior cranial fossa and cerebellum
      volumes can be measured by stereological methods, and the ratio of these
      measurements can contribute to the evaluation of chiari type I malformation
      cases.

PMID- 22629167
TI  - Long-term efficacy of prism adaptation on spatial neglect: preliminary results on
      different spatial components.
AB  - This study describes the long-term effectiveness on spatial neglect recovery of a
      2-week treatment based on prism adaptation (PA). Seven right-brain-damaged
      patients affected by chronic neglect were evaluated before, after two weeks of
      the PA treatment and at a follow-up (variable between 8 and 30 months after the
      end of PA). Neglect evaluation was performed by means of BIT (conventional and
      behavioral), Fluff Test, and Comb and Razor Test. The results highlight an
      improvement, after the PA training, in both tasks performed using the hand
      trained in PA treatment and in behavioral tasks not requiring a manual motor
      response. Such effects extend, even if not significantly, to all BIT subtests.
      These results support previous findings, showing that PA improves neglect also on
      imagery tasks with no manual component, and provide further evidence for long
      lasting efficacy of PA training. Dissociations have been found with regard to PA
      efficacy on peripersonal, personal, and representational neglect, visuospatial
      agraphia and neglect dyslexia. In particular, we found no significant differences
      between the pre-training and post-training PA session in personal neglect
      measures, and a poor recovery of neglect dyslexia after PA treatment. The
      recruitment of a larger sample could help to confirm the effectiveness of the
      prismatic lenses with regard to the different clinical manifestations of spatial
      neglect.

PMID- 22629168
TI  - Methane production and consumption in loess soil at different slope position.
AB  - Methane (CH(4)) production and consumption and soil respiration in loess soils
      collected from summit (Top), back slope (Middle), and slope bottom (Bottom)
      positions were assessed in laboratory incubations. The CH(4) production potential
      was determined under conditions which can occur in the field (relatively short
      term flooding periods with initially ambient O(2) concentrations), and the CH(4)
      oxidation potential was estimated in wet soils enriched with CH(4). None of the
      soils tested in this study emitted a significant amount of CH(4). In fact, the
      Middle and Bottom soils, especially at the depth of 20-40 cm, were a consistent
      sink of methane. Soils collected at different slope positions significantly
      differed in their methanogenic, methanotrophic, and respiration activities. In
      comparison with the Top position (as reference soil), methane production and both
      CO(2) production and O(2) consumption under flooding were significantly
      stimulated in the soil from the Middle slope position (P < 0.001), while they
      were reduced in the Bottom soil (not significantly, by 6 to 57%). All upper soils
      (0-20 cm) completely oxidized the added methane (5 kPa) during 9-11 days of
      incubation. Soils collected from the 20-40 cm at the Middle and Bottom slope
      positions, however, consumed significantly more CH(4) than the Top soil (P <
      0.001).

PMID- 22629169
TI  - The use of geostatistics in the study of floral phenology of Vulpia geniculata
      (L.) link.
AB  - Traditionally phenology studies have been focused on changes through time, but
      there exist many instances in ecological research where it is necessary to
      interpolate among spatially stratified samples. The combined use of Geographical
      Information Systems (GIS) and Geostatistics can be an essential tool for spatial
      analysis in phenological studies. Geostatistics are a family of statistics that
      describe correlations through space/time and they can be used for both
      quantifying spatial correlation and interpolating unsampled points. In the
      present work, estimations based upon Geostatistics and GIS mapping have enabled
      the construction of spatial models that reflect phenological evolution of Vulpia
      geniculata (L.) Link throughout the study area during sampling season. Ten
      sampling points, scattered throughout the city and low mountains in the "Sierra
      de Cordoba" were chosen to carry out the weekly phenological monitoring during
      flowering season. The phenological data were interpolated by applying the
      traditional geostatitical method of Kriging, which was used to elaborate weekly
      estimations of V. geniculata phenology in unsampled areas. Finally, the
      application of Geostatistics and GIS to create phenological maps could be an
      essential complement in pollen aerobiological studies, given the increased
      interest in obtaining automatic aerobiological forecasting maps.

PMID- 22629170
TI  - Asthma mortality inequalities in Brazil: tolerating the unbearable.
AB  - Asthma is responsible for a high morbidity, resulting in hospitalizations,
      recurrent asphyxiation, and eventually death. In Brazil, where asthma is the
      third cause of hospitalizations for clinical illnesses and the fourth cause of
      death from respiratory diseases, some 20% of the population present wheezing. We
      evaluated the asthma mortality rates in the period between 1998 and 2009, using
      linear regressions, using the National Mortality Database (Ministry of Health of
      Brazil). The annual mortality rate (per 100,000 inhabitants) ranged from 1.68 in
      1998 to 1.32 in 2009 (mean : 1.49). Brazil presents a slight tendency of
      reduction in asthma mortality. Asthma mortality rates trends declined in the most
      developed regions of the country: Midwest, South, and Southeast, but it increased
      in the underprivileged regions: North (not statistically significant) and
      Northeast. This terrible sort of inequality requires urgent reaction from the
      public health authorities.

PMID- 22629171
TI  - Applying neural networks to hyperspectral and multispectral field data for
      discrimination of cruciferous weeds in winter crops.
AB  - In the context of detection of weeds in crops for site-specific weed control, on
      ground spectral reflectance measurements are the first step to determine the
      potential of remote spectral data to classify weeds and crops. Field studies were
      conducted for four years at different locations in Spain. We aimed to distinguish
      cruciferous weeds in wheat and broad bean crops, using hyperspectral and
      multispectral readings in the visible and near-infrared spectrum. To identify
      differences in reflectance between cruciferous weeds, we applied three
      classification methods: stepwise discriminant (STEPDISC) analysis and two neural
      networks, specifically, multilayer perceptron (MLP) and radial basis function
      (RBF). Hyperspectral and multispectral signatures of cruciferous weeds, and wheat
      and broad bean crops can be classified using STEPDISC analysis, and MLP and RBF
      neural networks with different success, being the MLP model the most accurate
      with 100%, or higher than 98.1%, of classification performance for all the years.
      Classification accuracy from hyperspectral signatures was similar to that from
      multispectral and spectral indices, suggesting that little advantage would be
      obtained by using more expensive airborne hyperspectral imagery. Therefore, for
      next investigations, we recommend using multispectral remote imagery to explore
      whether they can potentially discriminate these weeds and crops.

PMID- 22629172
TI  - DC-SIGN (CD209) promoter -336 A/G (rs4804803) polymorphism associated with
      susceptibility of Kawasaki disease.
AB  - Kawasaki disease (KD) is characterized by systemic vasculitis of unknown
      etiology. High-dose intravenous immunoglobulin (IVIG) is the most effective
      therapy for KD to reduce the prevalence of coronary artery lesion (CAL)
      formation. Recently, the alpha2, 6 sialylated IgG was reported to interact with a
      lectin receptor, specific intracellular adhesion molecule-3 grabbing nonintegrin
      homolog-related 1 (SIGN-R1) in mice and dendritic cell-specific intercellular
      adhesion molecule-3 grabbing nonintegrin (DC-SIGN) in human, and to trigger an
      anti-inflammatory cascade. This study was conducted to investigate whether the
      polymorphism of DC-SIGN (CD209) promoter -336 A/G (rs4804803) is responsible for
      susceptibility and CAL formation in KD patients using Custom TaqMan SNP
      Genotyping Assays. A total of 521 subjects (278 KD patients and 243 controls)
      were investigated to identify an SNP of rs4804803, and they were studied and
      showed a significant association between the genotypes and allele frequency of
      rs4804803 in control subjects and KD patients (P = 0.004 under the dominant
      model). However, the promoter variant of DC-SIGN gene was not associated with the
      occurrence of IVIG resistance, CAL formation in KD. The G allele of DC-SIGN
      promoter -336 (rs4804803) is a risk allele in the development of KD.

PMID- 22629174
TI  - The chemoselective reduction of isoxazoline gamma-lactams through iminium Aza
      Diels-Alder reactions: a short-cut synthesis of aminols as valuable intermediates
      towards nucleoside derivatives.
AB  - Isoxazoline gamma-lactams are prepared starting from the regioisomeric
      cycloadducts of benzonitrile oxide to the N-alkyl 2-azanorbornenes taking
      advantage of the efficient catalytic oxidation by RuO(4). The reduction of the
      amide groups is easily conducted in the presence of LiAlH(4) under mild
      conditions, which allowed for the chemoselective reduction of the amide moiety
      followed by ring opening to afford the desired conformationally locked
      isoxazoline-carbocyclic aminols, as valuable intermediates for nucleoside
      synthesis.

PMID- 22629175
TI  - The chemical composition of endotoxin isolated from intestinal strain of
      Desulfovibrio desulfuricans.
AB  - Desulfovibrio desulfuricans anaerobes are constituents of human alimentary tract
      microflora. There are suggestions that they take part in the pathogenesis of
      periodontitis and some gastrointestinal inflammatory disorders, such as
      ulcerative colitis or Crohn's disease. Endotoxin is one of Gram-negative bacteria
      cellular components that influence these microorganisms pathogenicity. Endotoxin
      is a lipid-polisaccharide heteropolymer consisting of three elements: lipid A,
      core oligosaccharide, and O-specific polysaccharide, also called antigen-O. The
      biological activity of lipopolysaccharide (LPS) is determined by its structure.
      In this study, we show that rhamnose, fucose, mannose, glucose, galactose,
      heptose, and 2-keto-3-deoxyoctulosonic acid (Kdo) are constituents of D.
      desulfuricans endotoxin oligosaccharide core and O-antigen. Lipid A of these
      bacteria LPS is composed of glucosamine disaccharide substituted by 3-acyloxyacyl
      residues: ester-bound 3-(dodecanoyloxy)tetradecanoic, 3
      (hexadecanoyloxy)tetradecanoic acid, and amide-bound 3
      (tetradecanoyloxy)tetradecanoic acid.

PMID- 22629176
TI  - Histopathological analogies in chronic pulmonary lesions between cattle and
      humans: basis for an alternative animal model.
AB  - Most of the natural cases of pneumonia in feedlot cattle are characterized by a
      longer clinical course due to chronic lung lesions. Microscopically, these
      lesions include interstitial fibroplasia, bronchitis, bronchiectasis,
      bronchiolitis obliterans, and epithelial metaplasia of the airways. Herein, the
      aim was to review, under a medical perspective, the pathologic mechanisms
      operating in these chronic pneumonic lesions in calves. Based on the similarities
      of these changes to those reported in bronchiolitis obliterans/organising
      pneumonia (BO/OP) and chronic obstructive pulmonary disease (COPD) in human
      beings, calves are proposed as an alternative animal model.

PMID- 22629177
TI  - Partial purification and characterization of rhodanese from rainbow trout
      (Oncorhynchus mykiss) liver.
AB  - Cyanide is one of the most toxic substances present in a wide variety of food
      materials that are consumed by animals. Rhodanese, a ubiquitous enzyme, can
      catalyse the detoxification of cyanide by sulphuration reaction. In this study,
      rhodanese was partially purified and characterized from the liver tissue
      homogenate of the rainbow trout. The enzyme was active in a broad range of pH,
      from 5 to 12. The optimal activity was found at a high pH (pH 10.5), and the
      temperature optimum was 25  degrees C. The enzyme was heat labile, losing > 50%
      of relative activity after only 5 min of incubation at 40  degrees C. The K(m)
      values for KCN and Na(2)S(2)O(3) as substrates were 36.81 mM and 19.84 mM,
      respectively. Studies on the enzyme with a number of cations showed that the
      activity of the enzyme was not affected by Sn(2+), but Hg(2+), Ba(2+), Pb(2+),
      and Ca(2+) inhibited and Cu(2+) activated the enzyme with a concentration
      dependent manner.

PMID- 22629178
TI  - Impacts of horticultural mineral oils and two insecticide practices on population
      fluctuation of Diaphorina citri and spread of Huanglongbing in a citrus orchard
      in Sarawak.
AB  - Aspects of the incidence and spread of the citrus disease huanglongbing (HLB) in
      relation to the vector Diaphorina citri population fluctuation were studied from
      January 1999 to December 2001 seasons in a 0.8 ha citrus orchard at Jemukan (1
      degrees  33'N, 110 degrees  41'E), Southwest Sarawak in Malaysia. In relation to
      insecticide and horticultural mineral oils (HMOs) use, levels of HLB infection
      rose quite rapidly over the next 3 years in the unsprayed control and less
      rapidly in the other treatments such as imidacloprid, nC24HMO, and
      triazophos/cypermethrin/chlorpyrifos. Levels of HLB as determined by Polymerase
      Chain Reaction (PCR) were 42.2%, 9.4%, 11.4%, and 22.7%, respectively. The
      effects of nC(24)HMO and conventional pesticides on the citrus psyllid population
      and parasitoids in citrus orchard were also determined.

PMID- 22629173
TI  - Neurobiology, pathophysiology, and treatment of melatonin deficiency and
      dysfunction.
AB  - Melatonin is a highly pleiotropic signaling molecule, which is released as a
      hormone of the pineal gland predominantly during night. Melatonin secretion
      decreases during aging. Reduced melatonin levels are also observed in various
      diseases, such as types of dementia, some mood disorders, severe pain, cancer,
      and diabetes type 2. Melatonin dysfunction is frequently related to deviations in
      amplitudes, phasing, and coupling of circadian rhythms. Gene polymorphisms of
      melatonin receptors and circadian oscillator proteins bear risks for several of
      the diseases mentioned. A common symptom of insufficient melatonin signaling is
      sleep disturbances. It is necessary to distinguish between symptoms that are
      curable by short melatonergic actions and others that require extended actions
      during night. Melatonin immediate release is already effective, at moderate
      doses, for reducing difficulties of falling asleep or improving symptoms
      associated with poorly coupled circadian rhythms, including seasonal affective
      and bipolar disorders. For purposes of a replacement therapy based on longer
      lasting melatonergic actions, melatonin prolonged release and synthetic agonists
      have been developed. Therapies with melatonin or synthetic melatonergic drugs
      have to consider that these agents do not only act on the SCN, but also on
      numerous organs and cells in which melatonin receptors are also expressed.

PMID- 22629179
TI  - Evolutionary relationship between two firefly species, Curtos costipennis and C.
      okinawanus (Coleoptera, Lampyridae), in the Ryukyu Islands of Japan revealed by
      the mitochondrial and nuclear DNA sequences.
AB  - The phylogenetic relationship, biogeography, and evolutionary history of closely
      related two firefly species, Curtos costipennis and C. okinawanus, distributed in
      the Ryukyu Islands of Japan were examined based on nucleotide sequences of
      mitochondrial (2.2 kb long) and nuclear (1.1-1.2 kb long) DNAs. In these
      analyses, individuals were divided among three genetically distinct local groups,
      C. costipennis in the Amami region, C. okinawanus in the Okinawa region, and C.
      costipennis in the Sakishima region. Their mtDNA sequences suggested that
      ancestral C. costipennis population was first separated between the Central and
      Southern Ryukyu areas, and the northern half was then subdivided between C.
      costipennis in the Amami and C. okinawanus in the Okinawa. The application of the
      molecular evolutionary clocks of coleopteran insects indicated that their
      vicariance occurred 1.0-1.4 million years ago, suggesting the influence of
      submergence and subdivision of a paleopeninsula extending between the Ryukyu
      Islands and continental China through Taiwan in the early Pleistocene.

PMID- 22629180
TI  - Frequency and associated factors for anxiety and depression in pregnant women: a
      hospital-based cross-sectional study.
AB  - Antepartum anxiety and/or depression is a major public health problem globally.
      The aim of this study was to estimate the frequency of antepartum anxiety and/or
      depression among pregnant women. This was a cross-sectional study conducted in a
      tertiary care hospital among pregnant women. A total of 165 pregnant women were
      interviewed by a clinical psychologist using HADS for assessing anxiety and/or
      depression and also collected information regarding sociodemographic, obstetric,
      family relationships, and home environment. Out of the total of 165 pregnant
      women about 70 percent of them were either anxious and/or depressed. The
      increasing age of women (P-value = 0.073), not having any live birth (P-value =
      0.036), adverse pregnancy outcome in past including death of a child, stillbirth
      or abortion (P-value = 0.013), participant's role in household decision making (P
      value = 0.013), and domestic violence (verbal or physical abuse towards mother or
      children by any family member) (P-value = 0.123). Our study highlights that
      anxiety and/or depression is quite common among pregnant women. Therefore, there
      is a need to incorporate screening for anxiety and depression in the existing
      antenatal programs and development of strategies to provide practical support to
      those identified.

PMID- 22629181
TI  - Improving growth and productivity of Oleiferous Brassicas under changing
      environment: significance of nitrogen and sulphur nutrition, and underlying
      mechanisms.
AB  - Mineral nutrients are the integral part of the agricultural systems. Among
      important plant nutrients, nitrogen (N) and sulphur (S) are known essential
      elements for growth, development, and various physiological functions in plants.
      Oleiferous brassicas (rapeseed and mustard) require higher amounts of S in
      addition to N for optimum growth and yield. Therefore, balancing S-N
      fertilization, optimization of nutrient replenishment, minimization of nutrient
      losses to the environment, and the concept of coordination in action between S
      and N could be a significant strategy for improvement of growth and productivity
      of oleiferous brassicas. Additionally, positive interaction between S and N has
      been reported to be beneficial for various aspects of oilseed brassicas. The
      current paper updates readers on the significance of N and S for the improvement
      of plant growth, development, and productivity in detail. In addition, S-N
      nutrition-mediated control of major plant antioxidant defense system components
      involved in the removal and/or metabolism of stress-induced/generated reactive
      oxygen species in plants (hence, the control of plant growth, development, and
      productivity) has been overviewed.

PMID- 22629182
TI  - Pollen viability, pistil receptivity, and embryo development in hybridization of
      Nelumbo nucifera Gaertn.
AB  - Seed set is usually low and differs for different crosses of flower lotus
      (Nelumbo nucifera Gaertn.). The reasons remain unknown, and this has a negative
      impact on lotus breeding. To determine the causes, we carried out two crosses of
      flower lotus, that is, "Jinsenianhua" * "Qinhuaihuadeng" and "Qinhuaihuadeng" *
      "Jinsenianhua" and pollen viability, pistil receptivity, and embryo development
      were investigated. The pollen grains collected at 05:00-06:00 hrs had the highest
      viability, and the viabilities of "Jinsenianhua" and "Qinhuaihuadeng" were 20.6
      and 15.7%, respectively. At 4 h after artificial pollination, the number of
      pollen grains germinating on each stigma reached a peak: 63.0 and 17.2 per stigma
      in "Jinsenianhua" * "Qinhuaihuadeng" and "Qinhuaihuadeng" * "Jinsenianhua",
      respectively. At 1 d after artificial pollination, the percentages of normal
      embryos in the two crosses were 55.0 and 21.9%, respectively; however, at 11 d
      after pollination, the corresponding percentages were 20.8 and 11.2%. Seed sets
      of the two crosses were 17.9 and 8.0%, respectively. The results suggested that
      low pistil receptivity and embryo abortion caused low seed set in
      "Qinhuaihuadeng" * "Jinsenianhua", whereas low fecundity of "Jinsenianhua" *
      "Qinhuaihuadeng" was mainly attributable to embryo abortion.

PMID- 22629183
TI  - The spectrum of histopathological lesions in children presenting with steroid
      resistant nephrotic syndrome at a single center in Pakistan.
AB  - Steroid-resistant nephrotic syndrome (SRNS) is a common problem in pediatric
      nephrology practice. There is currently little information in the literature on
      the spectrum of histopathologic lesions in children presenting with SRNS in
      Pakistan. This study was designed to determine the histopathologic lesions in
      children presenting with SRNS at our center. The study was conducted at the
      Histopathology Department, Sindh Institute of Urology and Transplantation (SIUT)
      from January 2009 to August 2011. All children (<= 16 years) presenting with
      SRNS, in whom renal biopsies were performed, were included. Their demographic,
      clinical, laboratory, and histopathological data were retrieved from files and
      original renal biopsy forms. The results were analyzed by SPSS version 10.0. A
      total of 147 children were included. Of these, 91 (61.9%) were males and 56
      (38.1%) females, with male-to-female ratio of 1.6 : 1. The mean age was 7.03 +/-
      4.0 years (range: 6 months-16 years). The histopathological lesions seen on renal
      biopsies comprised of focal segmental glomerulosclerosis (FSGS) (38.5%), followed
      by minimal change disease (MCD) (23.2%), IgM nephropathy (IgMN) (13.6%),
      idiopathic mesangial proliferative GN (10.2%), membranous GN (8.2%), and
      mesangiocapillary GN (4.8%). Our results indicate that FSGS is the predominant
      lesion in children with SRNS, followed by MCD and IgMN.

PMID- 22629184
TI  - Erratic male meiosis resulting in 2n pollen grain formation in a 4x cytotype (2n
      = 28) of Ranunculus laetus Wall. ex Royle.
AB  - Two accessions were studied for male meiosis in Ranunculus laetus from the cold
      regions of Northwest Himalayas. One accession showed the presence of 14 bivalents
      at diakinesis and regular segregation of bivalents at anaphase I which lead to
      normal tetrad formation with four n microspores and consequently n pollen grains
      and 100% pollen fertility. Second accession from the same locality revealed the
      erratic meiosis characterized by the presence of all the 28 chromosomes as
      univalents in meiocytes at metaphase I. Univalent chromosomes failed to segregate
      during anaphases and produced restitution nuclei at meiosis I and II. These
      restitution nuclei resulted into dyads and triads which subsequently produced two
      types of apparently fertile pollen grains. On the basis of size, the two types of
      pollen grains were categorized as n (normal reduced) and 2n (unreduced, 1.5-times
      larger than the n pollen grains). The estimated frequency of 2n pollen grains
      from dyads and triads (61.59%) was almost the same as that of the observed one
      (59.90%), which indicated that 2n pollen grains in R. laetus were the result of
      dyads and triads. The present paper herein may provide an insight into the
      mechanisms of the formation of various intraspecific polyploids through sexual
      polyploidization in R. laetus.

PMID- 22629186
TI  - Characterisation of particulate matter emitted from cofiring of lignite and
      agricultural residues in a fixed-bed combustor.
AB  - This study is focused on the emission of fixed bed combustor batch operated. Real
      time analyser ELPI (electrical low-pressure impactor) system was used to size
      segregated particulate matter emission ranging from 40 nm to 10 MUm. The results
      show that total number concentration were 3.4 * 10(3), 1.6 * 10(4), and 1.5 *
      10(5) particles/cm(3) . kg(fuel), while total mass of particles were 12.2, 8.0,
      and 6.5 mg/Nm(3) . kg(fuel) for combustion of lignite, rice husk and bagasse,
      respectively. But it can be noticed that cofiring released more particulate
      matter. Meanwhile it was found that the effect of ratio of over-fired air to
      total air supply is more pronounced, since decrease in this ratio, the amount of
      particles are decreased significantly. For particle size distribution, it can be
      observed that submicron-sized particles dominate and the most prevailing size is
      in the range: 50 nm <D(p) < 100 nm, for lignite and agricultural residues.
      However, during cofiring of fuel mixture at 70% rice husk mass concentration, it
      is found that there are two major fractions of particle size; 40 nm <D(p) < 70 nm
      and 0.2 MUm <D(p) < 0.5 MUm. The analysis of particle morphology showed that the
      isolate shape of submicron particle produced during lignite combustion is
      characterised by different geometries such as round, capsule, rod, flake-like,
      whereas the spherical shape is obtained with combustion of rice husk.

PMID- 22629185
TI  - Glycerol carbonate: a novel biosolvent with strong ionizing and dissociating
      powers.
AB  - The activity of biocatalysts in nonaqueous solvents is related to the interaction
      of organic solvents with cells or enzymes. The behavior of proteins is strongly
      dependent on the protonation state of their ionizable groups, which ionization
      constants are greatly affected by the solvent. Due to the weak ionizing and
      dissociating powers of common organic solvents, the charge of the protein will
      change significantly when the protein is transferred from water to common organic
      solvents, resulting in protein denaturation. In this work, glycerol carbonate
      (GC) was synthesized, which ionizing and dissociating abilities were very close
      to those of water. Transesterification activities of Candida antarctica lipase B
      (CALB) in GC were comparable to those in water and remained constant during 4
      week storage. Bacillus subtilis and Saccharomyecs cerevisiae were cultured in
      liquid media containing GC with test tubes. In the medium containing low GC
      concentration, Bacillus subtilis and Saccharomyecs cerevisiae grew well as in a
      medium containing no organic solvent, but, in the medium containing high GC
      concentration, the growth of Bacillus subtilis and Saccharomyecs cerevisiae was
      suppressed. The results suggested that GC is a potential biosolvent, which has
      great significance to biocatalysis in nonaqueous solvents.

PMID- 22629187
TI  - Soft tissue reconstruction following hemipelvectomy: eight-year experience and
      literature review.
AB  - BACKGROUND AND OBJECTIVES: Hemipelvectomy is a major surgical procedure that
      associates with significant morbidity, functional impairment, and psychological
      and body image problem. Reconstruction of the defect is a challenged since a
      large amount of composite tissues are needed. We would like to share our eight
      year experience with massive pelvic resection and reconstruction. METHODS: A
      retrospective analysis of all cases of hemipelvectomy was conducted in our
      institution over eight-year period with particular attention given to the
      reconstruction choices and associated complications. RESULTS: Thirteen patients
      were included with median age of 39 years (range 13-78) of which all had advanced
      tumour with stage IIb (54%) and Stage III (46%). External hemipelvectomy was
      performed in all cases, and resultant defects were reconstructed with variety
      type of flaps. These include fillet thigh flaps, regional pedicle flaps of
      different designs, and free flap. CONCLUSIONS: Massive pelvic tumour is rarely
      encountered in our population but can be seen across all age groups and usually
      due to late presentation. The defects should be reconstructed using local or
      regional flaps, incorporating the muscle component to enhance flap perfusion. The
      tissue should be harvested from the amputated limb, as it can limit the donor
      site morbidity.

PMID- 22629188
TI  - Removal efficiency of Cr6+ by indigenous Pichia sp. isolated from textile factory
      effluent.
AB  - Resistance of the indigenous strains P. jadinii M9 and P. anomala M10, to high
      Cr(6+) concentrations and their ability to reduce chromium in culture medium was
      studied. The isolates were able to tolerate chromium concentrations up to 104 MUg
      mL(-1). Growth and reduction of Cr(6+) were dependent on incubation temperature,
      agitation, Cr(6+) concentration, and pH. Thus, in both studied strains the
      chromium removal was increased at 30  degrees C with agitation. The optimum pH
      was different, with values of pH 3.0 and pH 7.0 in the case of P. anomala M10 and
      pH 7.0 using P. jadinii M9. Chromate reduction occurred both in intact cells
      (grown in culture medium) as well as in cell-free extracts. Chromate reductase
      activity could be related to cytosolic or membrane-associated proteins. The
      presence of a chromate reductase activity points out a possible role of an enzyme
      in Cr(6+) reduction.

PMID- 22629189
TI  - Hepatitis C virus in Arab world: a state of concern.
AB  - Hepatitis C virus has been considered to be one of the most important devastating
      causes of chronic hepatitis, cirrhosis, and hepatic cellular carcinoma. The
      prevalence of such virus varies greatly over the world. Arab world has a unique
      geography and consists over nineteen countries who share the same heritage and
      customs and do speak the same language. In this area, the epidemiology of
      hepatitis C is not well understandable. Hepatitis C virus was found to be endemic
      in Arabia. The serostatus of such virus was found to be variable among these
      countries with uniform patterns of genotypes. Such prevalence varies tremendously
      according to the risk factors involved. Blood and blood products, haemodialysis,
      intravenous, and percutaneous drug users, and occupational, habitual, and social
      behavior were found to be the important factors involved. Hepatitis C will have
      major social, economic, and even political burdens on such young and dynamic
      societies. Thus, strategies and clear policy of intervention are urgently needed
      to combat the consequences of HCV both regionally and at state level of each
      country.

PMID- 22629190
TI  - Human keratinocyte growth and differentiation on acellular porcine dermal matrix
      in relation to wound healing potential.
AB  - A number of implantable biomaterials derived from animal tissues are now used in
      modern surgery. Xe-Derma is a dry, sterile, acellular porcine dermis. It has a
      remarkable healing effect on burns and other wounds. Our hypothesis was that the
      natural biological structure of Xe-Derma plays an important role in keratinocyte
      proliferation and formation of epidermal architecture in vitro as well as in
      vivo. The bioactivity of Xe-Derma was studied by a cell culture assay. We
      analyzed growth and differentiation of human keratinocytes cultured in vitro on
      Xe-Derma, and we compared the results with formation of neoepidermis in the deep
      dermal wounds treated with Xe-Derma. Keratinocytes cultured on Xe-Derma submerged
      in the culture medium achieved confluence in 7-10 days. After lifting the
      cultures to the air-liquid interface, the keratinocytes were stratified and
      differentiated within one week, forming an epidermis with basal, spinous,
      granular, and stratum corneum layers. Immunohistochemical detection of high
      molecular weight cytokeratins (HMW CKs), CD29, p63, and involucrin confirmed the
      similarity of organization and differentiation of the cultured epidermal cells to
      the normal epidermis. The results suggest that the firm natural structure of Xe
      Derma stimulates proliferation and differentiation of human primary keratinocytes
      and by this way improves wound healing.

PMID- 22629191
TI  - The influence of wildfires on aerosol size distributions in rural areas.
AB  - The number of particles and their size distributions were measured in a rural
      area, during the summer, using a PCASP-X. The aim was to study the influence of
      wildfires on particle size distributions. The comparative studies carried out
      reveal an average increase of around ten times in the number of particles in the
      fine mode, especially in sizes between 0.10 and 0.14 MUm, where the increase is
      of nearly 20 times. An analysis carried out at three different points in time-
      before, during, and after the passing of the smoke plume from the wildfires-
      shows that the mean geometric diameter of the fine mode in the measurements
      affected by the fire is smaller than the one obtained in the measurements carried
      out immediately before and after (0.14 MUm) and presents average values of 0.11
      MUm.

PMID- 22629192
TI  - Effect of ADH II deficiency on the intracellular redox homeostasis in Zymomonas
      mobilis.
AB  - Mutant strain of the facultatively anaerobic, ethanol-producing bacterium
      Zymomonas mobilis, deficient in the Fe-containing alcohol dehydrogenase isoenzyme
      (ADH II), showed impaired homeostasis of the intracellular NAD(P)H during
      transition from anaerobic to aerobic conditions, and also in steady-state
      continuous cultures at various oxygen supplies. At the same time, ADH II
      deficiency in aerobically grown cells was accompanied by a threefold increase of
      catalase activity and by about 50% increase of hydrogen peroxide excretion. It is
      concluded that ADH II under aerobic conditions functions to maintain
      intracellular redox homeostasis and to protect the cells from endogenous hydrogen
      peroxide.

PMID- 22629193
TI  - Monitoring resistance to spinosad in the melon fly (Bactrocera cucurbitae) in
      Hawaii and Taiwan.
AB  - Spinosad is a natural insecticide with desirable qualities, and it is widely used
      as an alternative to organophosphates for control of pests such as the melon fly,
      Bactrocera cucurbitae (Coquillett). To monitor the potential for development of
      resistance, information about the current levels of tolerance to spinosad in
      melon fly populations were established in this study. Spinosad tolerance
      bioassays were conducted using both topical applications and feeding methods on
      flies from field populations with extensive exposure to spinosad as well as from
      collections with little or no prior exposure. Increased levels of resistance were
      observed in flies from the field populations. Also, higher dosages were generally
      required to achieve specific levels of mortality using topical applications
      compared to the feeding method, but these levels were all lower than those used
      for many organophosphate-based food lures. Our information is important for
      maintaining effective programs for melon fly management using spinosad.

PMID- 22629194
TI  - Statistical evaluation and optimization of factors affecting the leaching
      performance of copper flotation waste.
AB  - Copper flotation waste is an industrial by-product material produced from the
      process of manufacturing copper. The main concern with respect to landfilling of
      copper flotation waste is the release of elements (e.g., salts and heavy metals)
      when in contact with water, that is, leaching. Copper flotation waste generally
      contains a significant amount of Cu together with trace elements of other toxic
      metals, such as Zn, Co, and Pb. The release of heavy metals into the environment
      has resulted in a number of environmental problems. The aim of this study is to
      investigate the leaching characteristics of copper flotation waste by use of the
      Box-Behnken experimental design approach. In order to obtain the optimized
      condition of leachability, a second-order model was examined. The best leaching
      conditions achieved were as follows: pH = 9, stirring time = 5 min, and
      temperature = 41.5  degrees C.

PMID- 22629196
TI  - Applying econometrics to the carbon dioxide "control knob".
AB  - This paper tests various propositions underlying claims that observed global
      temperature change is mostly attributable to anthropogenic noncondensing
      greenhouse gases, and that although water vapour is recognized to be a dominant
      contributor to the overall greenhouse gas (GHG) effect, that effect is merely a
      "feedback" from rising temperatures initially resulting only from "non
      condensing" GHGs and not at all from variations in preexisting naturally caused
      atmospheric water vapour (i.e., [H(2)O]). However, this paper shows that "initial
      radiative forcing" is not exclusively attributable to forcings from noncondensing
      GHG, both because atmospheric water vapour existed before there were any
      significant increases in GHG concentrations or temperatures and also because
      there is no evidence that such increases have produced measurably higher [H(2)O].
      The paper distinguishes between forcing and feedback impacts of water vapour and
      contends that it is the primary forcing agent, at much more than 50% of the total
      GHG gas effect. That means that controlling atmospheric carbon dioxide is
      unlikely to be an effective "control knob" as claimed by Lacis et al. (2010).

PMID- 22629195
TI  - Study of saiga horn using high-performance liquid chromatography with mass
      spectrometry.
AB  - The saiga horns have been investigated the using of modern analytic methods. High
      performance liquid chromatography (HPLC) with mass-spectrometric (MS and MS/MS)
      detection and polyacrylamide gel electrophoresis (PAGE) were used. It could be
      concluded that basic proteins of the saiga horns are keratins and collagen. The
      basic representation protein in all samples is keratin type I microfibrillar
      (from sheep), keratin type II microfibrillar (from sheep), collagen type I
      (alpha(1)) (from bovine) and collagen type I (alpha(2)) (from bovine). Free amino
      acids we determined in all samples are nontreated by enzyme.

PMID- 22629197
TI  - Freezing of oocytes and its effect on the displacement of the meiotic spindle:
      short communication.
AB  - Our investigations focused on spindle dynamics/displacement in frozen-thawed
      human oocytes. In each oocyte, prior to freezing and after thawing and culturing,
      the presence/location of the spindle was determined with the Polscope technique.
      A total of 259 oocytes have been thawed with a survival rate of 81.1%. From the
      210 survived oocytes, 165 were fertilized (78.6%) and 89.1% of them cleaved. A
      total of 143 embryos were transferred into 63 patients resulting in 11 clinical
      pregnancies (17.5%), 7 of which resulted in live birth of 8 babies (1 twin
      pregnancy). We were able to detect the spindle in 221 of 259 oocytes (85.3%).
      After thawing and culturing the oocytes, we were able to visualize the spindle in
      177 of 210 oocytes (84.3%). In 83 of these 177 oocytes, the spindle was observed
      to be in the same location as it was before cryopreservation (46.9%). However, in
      94 of these 177 oocytes (53.1%), the spindle reformed in a different
      position/location relative to the polar body. Our results show that after thawing
      and culture in half of the spindle-positive oocytes the spindle was detected in a
      new location, indicating that the spindle and the polar body move relative to
      each other.

PMID- 22629198
TI  - Removal of Pb (II) ions from aqueous solutions by Cladophora rivularis (Linnaeus)
      Hoek.
AB  - Biosorption of Pb(II) using Cladophora rivularis was examined as a function of
      initial pH heavy metal concentration and temperature. The optimum pH value for
      the biosorption of lead was 4.0. The adsorption equilibriums were well described
      by Langmuir and Freundlich isotherm models and it was implied by the results that
      the C. rivularis biomass is suitable for the development of efficient biosorbent
      in order to remove Pb(II) from wastewater and to recover it. The high values of
      correlation coefficient (R(2) = 0.984) demonstrate equilibrium data concerning
      algal biomass, which is well fitted in Freundlich isotherms model equations. The
      dimensionless parameter R(L) is found in the range of 0.0639 to 0.1925 (0 < R(L)
      < 1), which confirms the favorable biosorption process. Fourier transform infra
      red (FTIR) spectroscopy of C. rivularis was used to reveal the main function
      groups of biosorption, which were hydroxyl, amine groups, C-H stretching
      vibrations of -CH3 and -CH2, and complexation with functional groups. All these
      results suggest that C. rivularis can be used effectively for removal of Pb(II).

PMID- 22629199
TI  - Determination of the sampler type and rainfall effect on the deposition fluxes of
      the polychlorinated biphenyls.
AB  - Atmospheric concentration and deposition samples were collected between June 2008
      and June 2009 in an urban sampling site Yavuzselim, Turkey. Eighty-three
      polychlorinated biphenyl (PCB) congeners were targeted in the collected samples.
      It was found that 90% of the total PCB concentration was in the gas phase.
      Deposition samples were collected by a wet-dry deposition sampler (WDDS) and a
      bulk deposition sampler (BDS). Average total deposition fluxes measured with the
      BDS in dry periods was 5500 +/- 2400 pg/(m(2)day); average dry deposition fluxes
      measured by the WDDS in the same period were 6400 +/- 3300 pg/(m(2)day). The
      results indicated that the sampler type affected the measured flux values. Bulk
      deposition samples were also collected in rainy periods by using the BDS and the
      average flux value was 8700 +/- 3100 pg/(m(2)day). The measured flux values were
      lower than the values reported for the urban and industrial areas. Dry deposition
      velocities for the WDDS and BDS samples were calculated 0.48 +/- 0.35 cm/s and
      0.13 +/- 0.15 cm/s, respectively.

PMID- 22629200
TI  - Synthesis of new bitopic tetra(pyrazolyl)-ligands with neopentane and O-xylene
      backbones.
AB  - Several new bitopic pyrazole-containing ligands were prepared from the
      corresponding pyrazoles and tetrahalogen or tetratosyloxy derivatives of o-xylene
      and neopentane in a superbasic medium (KOH-DMSO).

PMID- 22629201
TI  - Interannual variation in root production in grasslands affected by artificially
      modified amount of rainfall.
AB  - The effect of different amounts of rainfall on the below-ground plant biomass was
      studied in three grassland ecosystems. Responses of the lowland (dry Festuca
      grassland), highland (wet Cirsium grassland), and mountain (Nardus grassland)
      grasslands were studied during five years (2006-2010). A field experiment based
      on rainout shelters and gravity irrigation simulated three climate scenarios:
      rainfall reduced by 50% (dry), rainfall increased by 50% (wet), and the natural
      rainfall of the current growing season (ambient). The interannual variation in
      root increment and total below-ground biomass reflected the experimentally
      manipulated amount of precipitation and also the amount of current rainfall of
      individual years. The effect of year on these below-ground parameters was found
      significant in all studied grasslands. In comparison with dry Festuca grassland,
      better adapted to drought, submontane wet Cirsium grassland was more sensitive to
      the different water inputs forming rather lower amount of below-ground plant
      matter at reduced precipitation.

PMID- 22629202
TI  - Implementing best practices and validation of cryopreservation techniques for
      microorganisms.
AB  - Authentic, well preserved living organisms are basic elements for research in the
      life sciences and biotechnology. They are grown and utilized in laboratories
      around the world and are key to many research programmes, industrial processes
      and training courses. They are vouchers for publications and must be available
      for confirmation of results, further study or reinvestigation when new
      technologies become available. These biological resources must be maintained
      without change in biological resource collections. In order to achieve best
      practice in the maintenance and provision of biological materials for industry,
      research and education the appropriate standards must be followed.
      Cryopreservation is often the best preservation method available to achieve these
      aims, allowing long term, stable storage of important microorganisms. To
      promulgate best practice the Organisation for Economic Development and Co
      operation (OECD published the best practice guidelines for BRCs. The OECD best
      practice consolidated the efforts of the UK National Culture Collections, the
      European Common Access to Biological Resources and Information (CABRI) project
      consortium and the World Federation for Culture Collections. The paper discusses
      quality management options and reviews cryopreservation of fungi, describing how
      the reproducibility and quality of the technique is maintained in order to retain
      the full potential of fungi.

PMID- 22629203
TI  - Quantification of sunscreen ethylhexyl triazone in topical skin-care products by
      normal-phase TLC/densitometry.
AB  - Ethylhexyl triazone (ET) was separated from other sunscreens such as avobenzone,
      octocrylene, octyl methoxycinnamate, and diethylamino hydroxybenzoyl hexyl
      benzoate and from parabens by normal-phase HPTLC on silica gel 60 as stationary
      phase. Two mobile phases were particularly effective: (A) cyclohexane-diethyl
      ether 1 : 1 (v/v) and (B) cyclohexane-diethyl ether-acetone 15 : 1 : 2 (v/v/v)
      since apart from ET analysis they facilitated separation and quantification of
      other sunscreens present in the formulations. Densitometric scanning was
      performed at 300 nm. Calibration curves for ET were nonlinear (second-degree
      polynomials), with R > 0.998. For both mobile phases limits of detection (LOD)
      were 0.03 and limits of quantification (LOQ) 0.1 MUg spot(-1). Both methods were
      validated.

PMID- 22629204
TI  - Effect of NPK fertilizer on chemical composition of pumpkin (Cucurbita pepo
      Linn.) seeds.
AB  - An investigation of the proximate composition and antioxidant profile of pumpkin
      seeds obtained from different levels of NPK 15 : 15 : 15 compound fertilizer
      application at the Obafemi Awolowo University, Ile-Ife, Nigeria was carried out.
      Pumpkin seeds were grown in 2010 for two cropping seasons (May to August and
      August to November), and the following fertilizer rates were applied: 0, 50, 100,
      150, 200, and 250 kg/ha. Standard analytical methods were used to determine
      protein, crude fibre, ash, fat, carbohydrate, antioxidant activities, phenol,
      flavonoid, proanthocyanidin, and anthocyanin. The highest concentrations of the
      proximate and antioxidants analysed were found from the seeds of control and
      those treated with lower NPK rates. The mean protein, ash, crude fibre, and
      carbohydrate values of pumpkin seeds at zero to 100 kg NPK/ha were 27%, 1.56%,
      0.56%, and 11.7% respectively. At these same levels of fertilizer, pumpkin seed
      oil yield was 59%. Antioxidant activities ranged from 89.9 to 90.4% while total
      phenol was 47 mg/100 g. Except for carbohydrate, the % concentration of nutrients
      and antioxidants in pumpkin seeds was significantly (P = 0.05) depressed with
      fertilizer rates above 100 g/ha.

PMID- 22629205
TI  - Reproductive ecology of Prochilodus brevis an endemic fish from the semiarid
      Region of Brazil.
AB  - The commercially important migratory fish Prochilodus brevis is from the
      Neotropical region, and understanding the reproductive ecology of this
      potamodromous fish is essential for its conservation and management. This study
      investigated the length-mass relationship, sex ratio, length at first gonadal
      maturity, gonadal development stages, gonadosomatic index, condition factor, and
      reproductive period of P. brevis. Temporal distribution of rainfall, temperature,
      dissolved oxygen concentration, pH, and electrical conductivity of the water were
      related to the reproductive period of this fish. Rainfall seems to be the main
      environmental factor which modulates changes in limnological parameters and the
      timing of the spawning period of this fish. P. brevis migrates into lower reaches
      of the river to feed during the dry season and returns to the upper reaches
      during the rainy season to spawn. Inadequate facilities for migration create
      obstacles for spawning success of this ecologically important fish.

PMID- 22629206
TI  - The influence of season on the gonad index and biochemical composition of the sea
      urchin Paracentrotus lividus from the Golf of Tunis.
AB  - Seasonal variation in the gonad weight and biochemical composition of the sea
      urchin Paracentrotus lividus from the Golf of Tunis (Tunisia) were studied
      between September 2003 and August 2004. The highest gonad indices occurred in
      March (16.71%). The spawning period occurred between April and July and resulted
      in a fall in gonad indices to low level (7.12 +/- 0.12%). Protein constituted the
      main component of the gonad, and lipid and carbohydrate were found at appreciable
      amounts. Consistent with the gonad cycle, sea urchin biochemical components
      showed clear seasonal variation with a significant decrease during the spawning
      period. The polyunsaturated fatty acid (PUFA) group was found at high level (40%
      of the total fatty acids). Of the PUFA group, eicosapentaenoic (C20:5 n - 3) and
      eicosatetraenoic (C20:4 n - 3) were the most abundant gonadal lipids. The level
      of PUFA was significantly affected by temperature variation showing an increase
      during the cold months and a decrease in the hot months.

PMID- 22629207
TI  - Occurrence of the foramen of Vesalius and its morphometry relevant to clinical
      consideration.
AB  - All 377 dry skulls were examined for the occurrence and morphometry of the
      foramen of Vesalius (FV) both in the middle cranial fossa and at the extracranial
      view of the skull base. There were 25.9% and 10.9% of FV found at the
      extracranial view of the skull base and in the middle cranial fossa,
      respectively. Total patent FV were 16.1% (11.9% unilaterally and 4.2%
      bilaterally). Most FV were found in male and on the left side. Comparatively, FV
      at the extracranial view of the skull base had a larger maximum diameter. The
      distance between FV and the foramen ovale (FO) was as short as 2.05 +/- 1.09 mm
      measured at the extracranial view of the skull base. In conclusion, although the
      existence of FV is inconstant, its occurrence could not be negligible. The
      proximity of FV to FO should remind neurosurgeons to be cautious when performing
      the surgical approach through FO.

PMID- 22629208
TI  - New insights in the sugarcane transcriptome responding to drought stress as
      revealed by superSAGE.
AB  - In the scope of the present work, four SuperSAGE libraries have been generated,
      using bulked root tissues from four drought-tolerant accessions as compared with
      four bulked sensitive genotypes, aiming to generate a panel of differentially
      expressed stress-responsive genes. Both groups were submitted to 24 hours of
      water deficit stress. The SuperSAGE libraries produced 8,787,315 tags (26 bp)
      that, after exclusion of singlets, allowed the identification of 205,975 unitags.
      Most relevant BlastN matches comprised 567,420 tags, regarding 75,404 unitags
      with 164,860 different ESTs. To optimize the annotation efficiency, the Gene
      Ontology (GO) categorization was carried out for 186,191 ESTs (BlastN against
      Uniprot-SwissProt), permitting the categorization of 118,208 ESTs (63.5%). In an
      attempt to elect a group of the best tags to be validated by RTqPCR, the GO
      categorization of the tag-related ESTs allowed the in silico identification of
      213 upregulated unitags responding basically to abiotic stresses, from which 145
      presented no hits after BlastN analysis, probably concerning new genes still
      uncovered in previous studies. The present report analyzes the sugarcane
      transcriptome under drought stress, using a combination of high-throughput
      transcriptome profiling by SuperSAGE with the Solexa sequencing technology,
      allowing the identification of potential target genes during the stress response.

PMID- 22629211
TI  - Influence of growth regulators on callogenesis and somatic embryo development in
      date palm (Phoenix dactylifera L.) Sahelian cultivars.
AB  - This study provides a physiological analysis of somatic embryogenesis in four
      elite cultivars of date palms: Ahmar, Amsekhsi, Tijib, and Amaside, from the
      initial callogenesis to establishment and proliferation of embryogenic suspension
      cultures. Somatic embryos development and in vitro plants rooting were also
      studied. For each step, auxins and cytokinins concentrations were optimised. The
      primary callogenesis from leaf explants of seedlings appeared highly dependent on
      genotype. Ahmar (80%) and Amsekhsi (76%) appeared highly callogenic, whereas
      Tijib (10%) and Amaside (2%) produced low amounts of calluses. 2,4
      Dichlorophenoxyacetic acid appeared favorable to the induction of primary
      callogenesis and its effect was enhanced by the addition of benzyl adenine or
      adenine sulfate. Secondary friable calli obtained from chopped granular calli
      were used to initiate embryogenic cell suspensions in media supplied with 2,4
      dichlorophenoxyacetic acid. Suspension cultures showed a growth rate of fourfold
      after four subcultures in presence of 2,4-dichlorophenoxyacetic acid 2 mg/L. Our
      results showed that a seven-day transitory treatment with benzyl adenine 0,5 mg/L
      was necessary to optimize embryos development. Naphthalene acetic acid induced
      the development of primary orthogravitropic roots during embryos germination. The
      comparison with cytofluorometry of nuclear DNA amounts showed no significant
      difference in ploidy level between regenerated plants and seedlings.

PMID- 22629210
TI  - The relationship between trabecular bone structure modeling methods and the
      elastic modulus as calculated by FEM.
AB  - Trabecular bone cores were collected from the femoral head at the time of surgery
      (hip arthroplasty). Investigated were 42 specimens, from patients with
      osteoporosis and coxarthrosis. The cores were scanned used computer
      microtomography (microCT) system at an isotropic spatial resolution of 36
      microns. Image stacks were converted to finite element models via a bone voxel-to
      element algorithm. The apparent modulus was calculated based on the assumptions
      that for the elastic properties, E = 10 MPa and nu = 0.3. The compressive
      deformation as calculated by finite elements (FE) analysis was 0.8%. The models
      were coarsened to effectively change the resolution or voxel size (from 72
      microns to 288 microns or from 72 microns to 1080 microns). The aim of our study
      is to determine how an increase in the distance between scans changes the elastic
      properties as calculated by FE models. We tried to find a border value voxel size
      at which the module values were possible to calculate. As the voxel size
      increased, the mean voxel volume increased and the FEA-derived apparent modulus
      decreased. The slope of voxel size versus modulus relationship correlated with
      several architectural indices of trabecular bone.

PMID- 22629209
TI  - Serotonin receptors in hippocampus.
AB  - Serotonin is an ancient molecular signal and a recognized neurotransmitter
      brainwide distributed with particular presence in hippocampus. Almost all
      serotonin receptor subtypes are expressed in hippocampus, which implicates an
      intricate modulating system, considering that they can be localized as
      autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within
      the same cell and being target of homo- and heterodimerization. Neurons and glia,
      including immune cells, integrate a functional network that uses several
      serotonin receptors to regulate their roles in this particular part of the limbic
      system.

PMID- 22629212
TI  - Are ancient durum wheats less toxic to celiac patients? A study of alpha-gliadin
      from Graziella Ra and Kamut.
AB  - In the present paper, the controversial hypothesis suggesting ancient grains
      might show lower immunogenic properties and therefore the possibility to
      introduce them in the diet of wheat-sensitive people, including celiac patients,
      was investigated. The immunogenic potential of the ancient durum wheats Graziella
      Ra and Kamut was studied by comparison to the durum accessions Cappelli,
      Flaminio, Grazia and Svevo. Experiments were carried out with two monoclonal
      antibodies (mAbs) raised against alpha-gliadin peptides p31-49 and p56-75 (the
      latter containing the overlapping DQ2-Glia-alpha1 and DQ2-Glia-alpha2 epitopes),
      toxic for celiac patients. For all accessions, a few alpha-gliadin alleles were
      also cloned, sequenced and translated into aminoacid sequences. Several aminoacid
      substitutions or deletions were detected in p31-49, DQ2-Glia-alpha1 and DQ2-Glia
      alpha2 epitopes, nevertheless, ELISA constantly showed antibody-antigen positive
      reactions which led us to suggest that mAbs binding was not apparently affected
      by polymorphisms. Moreover, a few substitutions were also observed in DQ2-Glia
      alpha3 and DQ8-Glia-alpha1 epitopes. Although some DQ2-Glia-alpha1 and DQ2-Glia
      alpha2 variants evidenced herein were previously reported to have a diminished or
      abolished T cell stimulatory capacity, present results cannot confirm that
      ancient durum wheats would be less CD-toxic. In conclusion, we strongly advice
      celiac patients from consuming ancient wheats including Graziella Ra or Kamut.

PMID- 22629213
TI  - Psychological profile in children and adolescents with severe course Juvenile
      Idiopathic Arthritis.
AB  - OBJECTIVE: Juvenile Idiopathic Arthritis (JIA) is the most common chronic
      pediatric rheumatic disease. It is recognized that only reliance on clinical
      signs of disease outcome is inadequate for understanding the impact of illness
      and its treatment on child's life and functioning. There is a need for a
      multidisciplinary and holistic approach to children with arthritis which
      considers both physical and emotional functioning. This study investigated the
      psychosocial functioning of children and adolescent with JIA and the disease
      related changes in their family. METHODS: The sample consisted of 33 hospitalized
      patients, aged 6-16 years. Both parents and the children were given a number of
      questionnaire to fill out. Clinical information was extracted from the
      interviews. RESULTS: Self-reported psychological functioning (depression,
      anxiety, and behavior) was not different from the normal population; however
      significant psychological suffering was detected by the clinical interview.
      CONCLUSIONS: Children and adolescents with JIA do not show overt psychopathology
      by structured assessment; nevertheless a more clinically oriented holistic
      approach confirms JIA as a disrupting event causing relevant changes in the
      quality of life of the affected families.

PMID- 22629214
TI  - Attitudes regarding the use of ventilator support given a supposed terminal
      condition among community-dwelling Mexican American and non-Hispanic white older
      adults: a pilot study.
AB  - PURPOSE: To determine the factors that are associated with Mexican Americans'
      preference for ventilator support, given a supposed terminal diagnosis. METHODS:
      100 Mexican Americans, aged 60-89, were recruited and screened for MMSE scores
      above 18. Eligible subjects answered a questionnaire in their preferred language
      (English/Spanish) concerning ventilator use during terminal illness. Mediator
      variables examined included demographics, generation, religiosity, occupation,
      self-reported depression, self-reported health, and activities of daily living.
      RESULTS: Being first or second generation American (OR = 0.18, CI = 0.05-0.66)
      with no IADL disability (OR = 0.11, CI = 0.02-0.59) and having depressive
      symptoms (OR = 1.43, CI = 1.08-1.89) were associated with preference for
      ventilator support. IMPLICATIONS: First and second generation older Mexican
      Americans and those functionally independent are more likely to prefer end-of
      life ventilation support. Although depressive symptoms were inversely associated
      with ventilator use at the end of life, scores may more accurately reflect
      psychological stress associated with enduring the scenario. Further studies are
      needed to determine these factors' generalizability to the larger Mexican
      American community.

PMID- 22629216
TI  - Study of enzymatic hydrolysis of fructans from Agave salmiana characterization
      and kinetic assessment.
AB  - Fructans were extracted from Agave salmiana juice, characterized and subjected to
      hydrolysis process using a commercial inulinase preparation acting freely. To
      compare the performance of the enzymatic preparation, a batch of experiments were
      also conducted with chicory inulin (reference). Hydrolysis was performed for 6 h
      at two temperatures (50, 60  degrees C) and two substrate concentrations (40, 60
      mg/ml). Hydrolysis process was monitored by measuring the sugars released and
      residual substrate by HPLC. A mathematical model which describes the kinetics of
      substrate degradation as well as fructose production was proposed to analyze the
      hydrolysis assessment. It was found that kinetics were significantly influenced
      by temperature, substrate concentration, and type of substrate (P < 0.01). The
      extent of substrate hydrolysis varied from 82 to 99%. Hydrolysis product was
      mainly constituted of fructose, obtaining from 77 to 96.4% of total reducing
      sugars.

PMID- 22629215
TI  - Siderophore-producing bacteria from a sand dune ecosystem and the effect of
      sodium benzoate on siderophore production by a potential isolate.
AB  - Bioremediation in natural ecosystems is dependent upon the availability of
      micronutrients and cofactors, of which iron is one of the essential elements.
      Under aerobic and alkaline conditions, iron oxidizes to Fe(+3) creating iron
      deficiency. To acquire this essential growth-limiting nutrient, bacteria produce
      low-molecular-weight, high-affinity iron chelators termed siderophores. In this
      study, siderophore-producing bacteria from rhizosphere and nonrhizosphere areas
      of coastal sand dunes were isolated using a culture-dependent approach and were
      assigned to 8 different genera with the predominance of Bacillus sp. Studies on
      the ability of these isolates to grow on sodium benzoate revealed that a
      pigmented bacterial culture TMR2.13 identified as Pseudomonas aeruginosa showed
      growth on mineral salts medium (MSM) with 2% of sodium benzoate and produced a
      yellowish fluorescent siderophore identified as pyoverdine. This was inhibited
      above 54 MUM of added iron in MSM with glucose without affecting growth, while,
      in presence of sodium benzoate, siderophore was produced even up to the presence
      of 108 MUM of added iron. Increase in the requirement of iron for metabolism of
      aromatic compounds in ecosystems where the nutrient deficiencies occur naturally
      would be one of the regulating factors for the bioremediation process.

PMID- 22629217
TI  - Examining the aftereffects of Hurricane Katrina in New Orleans: a qualitative
      study of faculty and staff perceptions.
AB  - Researchers have reported how Hurricane Katrina has affected teachers who work
      with Kindergarten to Grade 12 (K-12), yet little is known about how the natural
      disaster has affected other important K-12 faculty and staff (e.g., coaches,
      librarians, school counselors, and cafeteria workers). Missing from the
      literature is the impact that this natural disaster has had on these formal
      (school counselors) and informal (coaches, librarians) helpers of K-12 students.
      Using a focus group methodology, the authors examined the aftereffects of
      Hurricane Katrina on 12 school employees in New Orleans, Louisiana, 18 months
      after the hurricane. Informed by qualitative content analysis, three emergent
      themes were identified: emotion-focused aftereffects, positive coping, and worry
      and fear. The implications for future research and promoting hope in mental
      health counseling are discussed.

PMID- 22629218
TI  - Alzheimer's disease and risk of hip fracture: a meta-analysis study.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in the
      elderly population. Growing evidence supports that AD patients are at high risk
      for hip fracture, but the issue remains questionable. The purpose of the present
      study is to perform a meta-analysis to explore the association between AD and
      risk of hip fracture. Considering that bone mineral density (BMD) acts as a
      strong predictor of bone fracture, we also studied the hip BMD in AD patients.
      METHODS: We searched all publications in Medline, SciVerse Scopus, and Cochrane
      Library published up to January 2012 about the association between AD and hip
      fracture or hip BMD. RESULTS: There are 9 studies included in the meta-analysis.
      The results indicate that AD patients are at higher risk for hip fracture (OR and
      95% CI fixed: ES = 2.58, 95% CI = [2.03, 3.14]; dichotomous data: summary OR =
      1.80, 95% CI = [1.54, 2.11]) than healthy controls. Further meta-analysis showed
      that AD patients have a lower hip BMD (summary SMD = -1.12, 95% CI = [-1.34, 
      0.90]) than healthy controls. CONCLUSIONS: It was found that in comparison with
      healthy controls AD patients are at higher risk for hip fracture and have lower
      hip BMD.

PMID- 22629219
TI  - Preparation and in vitro evaluation of tacrolimus-loaded ethosomes.
AB  - The main objective of the present work was to prepare and assess dermal delivery
      of tacrolimus-loaded ethosomes versus classic liposomes. Both delivery systems
      were characterized for particle size, polydispersity index, and entrapment
      efficiency (EE), by dynamic laser diffraction and ultrafiltration or dialysis
      methods, respectively. The results indicated that presence of ethanol in the
      formulations affected the particle size. In addition, ultrafiltration method was
      selected to determine EE due to relatively short period as compared with dialysis
      method. Ethosomes exhibited a significant higher EE and amount of drug in dermis
      in contrast to classic liposomes suggesting that ethosomes with higher entrapment
      capacity prompted more amount of tacrolimus to permeate through stratum corneum
      and reach the target of atopic dermatitis (AD). Physical stability was very well
      for tacrolimus-loaded ethosomes under storage condition (4  degrees C). Our
      results demonstrated that the ethosomal system might be a promising candidate for
      dermal delivery of tacrolimus for AD.

PMID- 22629220
TI  - Segmentation of the breast skin and its influence in the simulation of the breast
      compression during an X-ray mammography.
AB  - A novel method of skin segmentation is presented aimed to obtain as many pixels
      belonging to the real skin as possible. This method is validated by experts in
      radiology. In addition, a biomechanical model of the breast, which considers the
      skin segmented in this way, is constructed to study the influence of considering
      real skin in the simulation of the breast compression during an X-ray
      mammography. The reaction forces of the plates are obtained and compared with the
      reaction forces obtained using classical methods that model the skin as a 2D
      membranes that cover all the breast. The results of this work show that, in most
      of the cases, the method of skin segmentation is accurate and that real skin
      should be considered in the simulation of the breast compression during the X-ray
      mammographies.

PMID- 22629221
TI  - Production of gymnemic acid depends on medium, explants, PGRs, color lights,
      temperature, photoperiod, and sucrose sources in batch culture of Gymnema
      sylvestre.
AB  - Gymnema sylvestre (R.Br.) is an important diabetic medicinal plant which yields
      pharmaceutically active compounds called gymnemic acid (GA). The present study
      describes callus induction and the subsequent batch culture optimization and GA
      quantification determined by linearity, precision, accuracy, and recovery. Best
      callus induction of GA was noticed in MS medium combined with 2,4-D (1.5 mg/L)
      and KN (0.5 mg/L). Evaluation and isolation of GA from the calluses derived from
      different plant parts, namely, leaf, stem and petioles have been done in the
      present case for the first time. Factors such as light, temperature, sucrose, and
      photoperiod were studied to observe their effect on GA production. Temperature
      conditions completely inhibited GA production. Out of the different sucrose
      concentrations tested, the highest yield (35.4 mg/g d.w) was found at 5% sucrose
      followed by 12 h photoperiod (26.86 mg/g d.w). Maximum GA production (58.28 mg/g
      d.w) was observed in blue light. The results showed that physical and chemical
      factors greatly influence the production of GA in callus cultures of G.
      sylvestre. The factors optimized for in vitro production of GA during the present
      study can successfully be employed for their large-scale production in
      bioreactors.

PMID- 22629223
TI  - Covering materials incorporating radiation-preventing techniques to meet
      greenhouse cooling challenges in arid regions: a review.
AB  - Cooling greenhouses is essential to provide a suitable environment for plant
      growth in arid regions characterized by brackish water resources. However, using
      conventional cooling methods are facing many challenges. Filtering out near infra
      red radiation (NIR) at the greenhouse cover can significantly reduce the heating
      load and can solve the overheating problem of the greenhouse air. This paper is
      to review (i) the problems of using conventional cooling methods and (ii) the
      advantages of greenhouse covers that incorporate NIR reflectors. This survey
      focuses on how the cover type affects the transmittance of photosynthetically
      active radiation (PAR), the reflectance or absorptance of NIR and the greenhouse
      air temperature. NIR-reflecting plastic films seem to be the most suitable, low
      cost and simple cover for greenhouses under arid conditions. Therefore, this
      review discusses how various additives should be incorporated in plastic film to
      increase its mechanical properties, durability and ability to stand up to
      extremely harsh weather. Presently, NIR-reflecting covers are able to reduce
      greenhouse air temperature by no more than 5  degrees C. This reduction is not
      enough in regions where the ambient temperature may exceed 45  degrees C in
      summer. There is a need to develop improved NIR-reflecting plastic film covers.

PMID- 22629222
TI  - Exercise and physical activity in the therapy of substance use disorders.
AB  - Exercise and physical activity are constantly gaining attention as adjuvant
      treatment for substance use disorders, supplementing classical pharmacological
      and psychotherapeutic approaches. The present work reviews studies addressing the
      therapeutic effects of exercise in alcohol abuse/dependence, nicotine
      abuse/dependence, and illicit drug abuse/dependence. In the field of smoking
      cessation, evidence is strong for exercise as an effective adjuvant treatment,
      whereas no generalizable and methodologically strong studies have been published
      for alcohol and drug treatment so far, allowing only preliminary conclusions
      about the effectiveness of exercise in these disorders. A couple of potential
      mechanisms are discussed, by which exercise may act as an effective treatment, as
      well as future directions for studies investigating exercise as a treatment
      strategy for substance use disorders.

PMID- 22629224
TI  - Program implementers' evaluation of the project P.A.T.H.S.: findings based on
      different datasets over time.
AB  - This paper integrates the evaluation findings based on program implementers in
      nine datasets collected from 2005 to 2009 (244 schools and 7,926 implementers).
      Using consolidated data with schools as the unit of analysis, results showed that
      program implementers generally had positive perceptions of the program,
      themselves, and benefits of the program, with more than four-fifths of the
      implementers regarding the program as beneficial to the program participants. The
      subjective outcome evaluation instrument was found to be internally consistent.
      Multiple regression analyses revealed that perceived qualities of the program and
      program implementers predicted perceived effectiveness of the program. In
      conjunction with evaluation findings based on other sources, the present study
      provides support for the effectiveness of the Tier 1 Program of the Project
      P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in
      Hong Kong.

PMID- 22629225
TI  - Comparison of effectiveness of supervised exercise program and Cyriax
      physiotherapy in patients with tennis elbow (lateral epicondylitis): a randomized
      clinical trial.
AB  - OBJECTIVE: To compare the effectiveness of supervised exercise program and Cyriax
      physiotherapy in the treatment of tennis elbow (lateral epicondylitis). DESIGN:
      Randomized clinical trial. SETTING: Physiotherapy and rehabilitation centre.
      SUBJECTS: This study was carried out with 20 patients, who had tennis elbow
      (lateral epicondylitis). INTERVENTION: Group A (n = 10) had received supervised
      exercise program. Group B (n = 10) was treated with Cyriax physiotherapy. All
      patients received three treatment sessions per week for four weeks (12 treatment
      sessions). OUTCOME MEASURES: Pain was evaluated using a visual analogue scale
      (VAS), and functional status was evaluated by completion of the Tennis Elbow
      Function Scale (TEFS) which were recorded at base line and at the end of fourth
      week. RESULTS: Both the supervised exercise program and Cyriax physiotherapy were
      found to be significantly effective in reduction of pain and in the improvement
      of functional status. The supervised exercise programme resulted in greater
      improvement in comparison to those who received Cyriax physiotherapy. CONCLUSION:
      The results of this clinical trial demonstrate that the supervised exercise
      program may be the first treatment choice for therapist in managing tennis elbow.

PMID- 22629226
TI  - Aerosol pollution from small combustors in a village.
AB  - Urban air pollution is widely recognized. Recently, there have been a few
      projects that examined air quality in rural areas (e.g., AUPHEP project in
      Austria, WOODUSE project in Denmark). Here we present the results within the
      International Cooperation Project RER/2/005 targeted at studying the effect of
      local combustion processes to air quality in the village of Brzezina in the
      countryside north-west of Wroclaw (south western Poland). We identified the
      potential emission sources and quantified their contributions. The ambient
      aerosol monitoring (PM(10) and elemental concentrations) was performed during 4
      measurement cycles, in summer 2009, 2010 and in winter 2010, 2011. Some receptor
      modeling techniques, factor analysis-multiple linear regression analysis (FA
      MLRA) and potential source localization function (PSLF), have been used.
      Different types of fuel burning along with domestic refuse resulted in an
      increased concentration of PM(10) particle mass, but also by an increased in
      various other compounds (As, Pb, Zn). Local combustion sources contributed up to
      80% to PM(10) mass in winter. The effect of other sources was small, from 6 to
      20%, dependently on the season. Both PM(10) and elemental concentrations in the
      rural settlement were comparable to concentrations at urban sites in summer and
      were much higher in winter, which can pose asignificant health risk to its
      inhabitants.

PMID- 22629228
TI  - Soluble sugars and sucrose-metabolizing enzymes related to cold acclimation of
      sweet cherry cultivars grafted on different rootstocks.
AB  - The bark tissues were collected from 4-year-old sweet cherry trees cvs. 0900
      Ziraat and Lambert grafted on Gisela 5 and Mazzard rootstocks in cold-acclimated
      (CA) and nonacclimated (NA) stages. Bark tissues subjected to 4  degrees C and -5
      degrees C injured to a limited extent in both stages. However, more than 50%
      injury occurred by temperatures equal to or colder than -15  degrees C only in NA
      period. Total soluble sugar (TSS), reducing sugars, and sucrose contents were
      higher in CA than those in NA stages in all samples. The activities of acid
      invertase (EC 3.2.1.26) and sucrose synthase (SS) (EC 2.4.2.13) enzymes were
      higher in NA stage than those in CA stage. Considering the rootstocks, reducing
      sugars were higher in both cultivars grafted on Gisela 5 whereas sucrose contents
      were higher in both cultivars grafted on Mazzard. However, the enzyme activities
      of both cultivars were higher on Mazzard rootstock than on Gisela 5. In
      conclusion, cold hardiness of sweet cherry graft combinations was suggested by
      increasing their TSS, reducing sugars, and sucrose contents significantly in the
      CA stage. Moreover, acid invertase and SS are down regulated during cold
      acclimation. Indeed the results suggested that Mazzard is more cold-hardy
      rootstock than Gisela 5.

PMID- 22629227
TI  - Cyclin d1 expression and its correlation with histopathological differentiation
      in oral squamous cell carcinoma.
AB  - BACKGROUND: Cyclin D1 regulates the G1 to S transition of cell cycle. Its
      deregulation or overexpression may lead to disturbance in the normal cell cycle
      control and tumour formation. Overexpression of cyclin D1 has been reported in
      various tumors of diverse histogenesis. This case control retrospective study was
      carried out to study the immunohistochemical reactivity and expression of cyclin
      D1 and its association with site, clinical staging, and histopathological
      differentiation of oral squamous cell carcinoma (OSCC). METHODS: Forty formalin
      fixed paraffin-embedded tissue blocks of biopsy specimens of oral squamous cell
      carcinoma were immunohistochemically evaluated for expression of cyclin D1.
      RESULTS: Cyclin D1 expression was seen in 45% cases of OSCC. It did not correlate
      with site and clinical staging. Highest expression was seen in well
      differentiated, followed by moderately differentiated, and poorly differentiated
      squamous cell carcinomas, with a statistically significant correlation.
      CONCLUSION: Cyclin D1 expression significantly increases with increase in
      differentiation.

PMID- 22629229
TI  - A model study on the possible effects of an external electrical field on enzymes
      having dinuclear iron cluster [2Fe-2S].
AB  - Hydrogenases which catalyze the H(2)<-> 2H(+) + 2e(-) reaction are metalloenzymes
      that can be divided into two classes, the NiFe and Fe enzymes, on the basis of
      their metal content. Iron-sulfur clusters [2Fe-2S] and [4Fe-4S] are common in
      ironhydrogenases. In the present model study, [2Fe-2S] cluster has been
      considered to visualize the effect of external electric field on various quantum
      chemical properties of it. In the model, all the cysteinyl residues are in the
      amide form. The PM3 type semiempirical calculations have been performed for the
      geometry optimization of the model structure in the absence and presence of the
      external field. Then, single point DFT calculations (B3LYP/6-31+G(d)) have been
      carried out. Depending on the direction of the field, the chemical reactivity of
      the model enzyme varies which suggests that an external electric field could,
      under proper conditions, improve the enzymatic hydrogen production.

PMID- 22629230
TI  - A systematic approach to pair secretory cargo receptors with their cargo suggests
      a mechanism for cargo selection by Erv14.
AB  - The endoplasmic reticulum (ER) is the site of synthesis of secreted and membrane
      proteins. To exit the ER, proteins are packaged into COPII vesicles through
      direct interaction with the COPII coat or aided by specific cargo receptors.
      Despite the fundamental role of such cargo receptors in protein traffic, only a
      few have been identified; their cargo spectrum is unknown and the signals they
      recognize remain poorly understood. We present here an approach we term "PAIRS"
      (pairing analysis of cargo receptors), which combines systematic genetic
      manipulations of yeast with automated microscopy screening, to map the spectrum
      of cargo for a known receptor or to uncover a novel receptor for a particular
      cargo. Using PAIRS we followed the fate of ~150 cargos on the background of
      mutations in nine putative cargo receptors and identified novel cargo for most of
      these receptors. Deletion of the Erv14 cargo receptor affected the widest range
      of cargo. Erv14 substrates have a wide array of functions and structures;
      however, they are all membrane-spanning proteins of the late secretory pathway or
      plasma membrane. Proteins residing in these organelles have longer transmembrane
      domains (TMDs). Detailed examination of one cargo supported the hypothesis that
      Erv14 dependency reflects the length rather than the sequence of the TMD. The
      PAIRS approach allowed us to uncover new cargo for known cargo receptors and to
      obtain an unbiased look at specificity in cargo selection. Obtaining the spectrum
      of cargo for a cargo receptor allows a novel perspective on its mode of action.
      The rules that appear to guide Erv14 substrate recognition suggest that sorting
      of membrane proteins at multiple points in the secretory pathway could depend on
      the physical properties of TMDs. Such a mechanism would allow diverse proteins to
      utilize a few receptors without the constraints of evolving location-specific
      sorting motifs.

PMID- 22629232
TI  - PAIRing up cargo proteins.

PMID- 22629231
TI  - The core apoptotic executioner proteins CED-3 and CED-4 promote initiation of
      neuronal regeneration in Caenorhabditis elegans.
AB  - A critical accomplishment in the rapidly developing field of regenerative
      medicine will be the ability to foster repair of neurons severed by injury,
      disease, or microsurgery. In C. elegans, individual visualized axons can be laser
      cut in vivo and neuronal responses to damage can be monitored to decipher genetic
      requirements for regeneration. With an initial interest in how local environments
      manage cellular debris, we performed femtosecond laser axotomies in genetic
      backgrounds lacking cell death gene activities. Unexpectedly, we found that the
      CED-3 caspase, well known as the core apoptotic cell death executioner, acts in
      early responses to neuronal injury to promote rapid regeneration of dissociated
      axons. In ced-3 mutants, initial regenerative outgrowth dynamics are impaired and
      axon repair through reconnection of the two dissociated ends is delayed. The CED
      3 activator, CED-4/Apaf-1, similarly promotes regeneration, but the upstream
      regulators of apoptosis CED-9/Bcl2 and BH3-domain proteins EGL-1 and CED-13 are
      not essential. Thus, a novel regulatory mechanism must be utilized to activate
      core apoptotic proteins for neuronal repair. Since calcium plays a conserved
      modulatory role in regeneration, we hypothesized calcium might play a critical
      regulatory role in the CED-3/CED-4 repair pathway. We used the calcium reporter
      cameleon to track in vivo calcium fluxes in the axotomized neuron. We show that
      when the endoplasmic reticulum calcium-storing chaperone calreticulin, CRT-1, is
      deleted, both calcium dynamics and initial regenerative outgrowth are impaired.
      Genetic data suggest that CED-3, CED-4, and CRT-1 act in the same pathway to
      promote early events in regeneration and that CED-3 might act downstream of CRT
      1, but upstream of the conserved DLK-1 kinase implicated in regeneration across
      species. This study documents reconstructive roles for proteins known to
      orchestrate apoptotic death and links previously unconnected observations in the
      vertebrate literature to suggest a similar pathway may be conserved in higher
      organisms.

PMID- 22629233
TI  - A prescription for improving drug formulary decision making.

PMID- 22629235
TI  - Crossing over...Markov meets Mendel.
AB  - Chromosomal crossover is a biological mechanism to combine parental traits. It is
      perhaps the first mechanism ever taught in any introductory biology class. The
      formulation of crossover, and resulting recombination, came about 100 years after
      Mendel's famous experiments. To a great extent, this formulation is consistent
      with the basic genetic findings of Mendel. More importantly, it provides a
      mathematical insight for his two laws (and corrects them). From a mathematical
      perspective, and while it retains similarities, genetic recombination guarantees
      diversity so that we do not rapidly converge to the same being. It is this
      diversity that made the study of biology possible. In particular, the problem of
      genetic mapping and linkage-one of the first efforts towards a computational
      approach to biology-relies heavily on the mathematical foundation of crossover
      and recombination. Nevertheless, as students we often overlook the mathematics of
      these phenomena. Emphasizing the mathematical aspect of Mendel's laws through
      crossover and recombination will prepare the students to make an early
      realization that biology, in addition to being experimental, IS a computational
      science. This can serve as a first step towards a broader curricular
      transformation in teaching biological sciences. I will show that a simple and
      modern treatment of Mendel's laws using a Markov chain will make this step
      possible, and it will only require basic college-level probability and calculus.
      My personal teaching experience confirms that students WANT to know Markov chains
      because they hear about them from bioinformaticists all the time. This entire
      exposition is based on three homework problems that I designed for a course in
      computational biology. A typical reader is, therefore, an instructional staff
      member or a student in a computational field (e.g., computer science,
      mathematics, statistics, computational biology, bioinformatics). However, other
      students may easily follow by omitting the mathematically more elaborate parts. I
      kept those as separate sections in the exposition.

PMID- 22629234
TI  - Reporting and methods in clinical prediction research: a systematic review.
AB  - BACKGROUND: We investigated the reporting and methods of prediction studies,
      focusing on aims, designs, participant selection, outcomes, predictors,
      statistical power, statistical methods, and predictive performance measures.
      METHODS AND FINDINGS: We used a full hand search to identify all prediction
      studies published in 2008 in six high impact general medical journals. We
      developed a comprehensive item list to systematically score conduct and reporting
      of the studies, based on recent recommendations for prediction research. Two
      reviewers independently scored the studies. We retrieved 71 papers for full text
      review: 51 were predictor finding studies, 14 were prediction model development
      studies, three addressed an external validation of a previously developed model,
      and three reported on a model's impact on participant outcome. Study design was
      unclear in 15% of studies, and a prospective cohort was used in most studies
      (60%). Descriptions of the participants and definitions of predictor and outcome
      were generally good. Despite many recommendations against doing so, continuous
      predictors were often dichotomized (32% of studies). The number of events per
      predictor as a measure of statistical power could not be determined in 67% of the
      studies; of the remainder, 53% had fewer than the commonly recommended value of
      ten events per predictor. Methods for a priori selection of candidate predictors
      were described in most studies (68%). A substantial number of studies relied on a
      p-value cut-off of p<0.05 to select predictors in the multivariable analyses
      (29%). Predictive model performance measures, i.e., calibration and
      discrimination, were reported in 12% and 27% of studies, respectively.
      CONCLUSIONS: The majority of prediction studies in high impact journals do not
      follow current methodological recommendations, limiting their reliability and
      applicability.

PMID- 22629236
TI  - Injury, disability and quality of life after the 2009 earthquake in Padang,
      Indonesia: a prospective cohort study of adult survivors.
AB  - BACKGROUND: On 30 September 2009, a 7.6 magnitude earthquake severely hit the
      coast of Padang city in West Sumatra, Indonesia leaving about 1,117 people dead
      and injuring another 3,515. Health consequences such as physical injury, co
      morbidity, disability and quality of life over time are seldom reported among
      survivors after earthquakes. OBJECTIVES: To investigate the associations between
      injury, disability and quality of life amongst adult survivors in Padang city
      after the 2009 earthquake. DESIGN/METHODS: A prospective cohort study was
      conducted to compare adult injured (184) and adult non-injured (93) subjects over
      a 6-month period. Data on physical injury, co-morbidities, disability and quality
      of life were collected through interviews and measured quantitatively in three
      phases, i.e. at baseline, end of 3 and 6 months. RESULTS: Disability scores were
      consistently and significantly higher among injured subjects compared to non
      injured, even when adjusted for co-morbidities (i.e. acute symptoms and chronic
      diseases). The highest disability score amongst injured subjects was attributed
      to 'feeling discomfort/pain'. Quality of life attribute (QLA) scores, were
      significantly lower amongst injured people as compared to those non-injured even
      when adjusted for co-morbidities. The lowest QLA item score amongst the injured
      was 'pain, depression and anxiety'. Significant and consistent negative
      correlations were found between disability and QLA scores in both the injured and
      non-injured groups. CONCLUSION: Physical injury is significantly correlated with
      both higher disability and lower quality of life, while disability has
      significant negative correlation with quality of life. The findings suggest that,
      through disability, injury may contribute to decreased quality of life. It is
      therefore recommended to promptly and adequately treat injuries after disasters
      to prevent any potential for disability and hence restore quality of life.

PMID- 22629237
TI  - Apoptosis of limb innervating motor neurons and erosion of motor pool identity
      upon lineage specific dicer inactivation.
AB  - Diversification of mammalian spinal motor neurons into hundreds of subtypes is
      critical for the maintenance of body posture and coordination of complex
      movements. Motor neuron differentiation is controlled by extrinsic signals that
      regulate intrinsic genetic programs specifying and consolidating motor neuron
      subtype identity. While transcription factors have been recognized as principal
      regulators of the intrinsic program, the role of posttranscriptional regulations
      has not been systematically tested. MicroRNAs produced by Dicer mediated cleavage
      of RNA hairpins contribute to gene regulation by posttranscriptional silencing.
      Here we used Olig2-cre conditional deletion of Dicer gene in motor neuron
      progenitors to examine effects of miRNA biogenesis disruption on postmitotic
      spinal motor neurons. We report that despite the initial increase in the number
      of motor neuron progenitors, disruption of Dicer function results in a loss of
      many limb- and sympathetic ganglia-innervating spinal motor neurons. Furthermore,
      it leads to defects in motor pool identity specification. Thus, our results
      indicate that miRNAs are an integral part of the genetic program controlling
      motor neuron survival and acquisition of subtype specific properties.

PMID- 22629238
TI  - Histamine h3 receptor: a novel therapeutic target in alcohol dependence?
AB  - The brain histaminergic system is one of the diffuse modulatory neurotransmitter
      systems which regulate neuronal activity in many brain areas. Studies on both
      rats and mice indicate that histamine H3 receptor antagonists decrease alcohol
      drinking in several models, like operant alcohol administration and drinking in
      the dark paradigm. Alcohol-induced place preference is also affected by these
      drugs. Moreover, mice lacking H3R do not drink alcohol like their wild type
      littermates, and they do not show alcohol-induced place preference. Although the
      mechanisms of these behaviors are still being investigated, we propose that H3R
      antagonists are promising candidates for use in human alcoholics, as these drugs
      are already tested for treatment of other disorders like narcolepsy and sleep
      disorders.

PMID- 22629239
TI  - An investigation of response and stimulus modality transfer effects after dual
      task training in younger and older.
AB  - It has been shown that dual-task training leads to significant improvement in
      dual-task performance in younger and older adults. However, the extent to which
      training benefits to untrained tasks requires further investigation. The present
      study assessed (a) whether dual-task training leads to cross-modality transfer in
      untrained tasks using new stimuli and/or motor responses modalities, (b) whether
      transfer effects are related to improved ability to prepare and maintain multiple
      task-set and/or enhanced response coordination, (c) whether there are age-related
      differences in transfer effects. Twenty-three younger and 23 older adults were
      randomly assigned to dual-task training or control conditions. All participants
      were assessed before and after training on three dual-task transfer conditions;
      (1) stimulus modality transfer (2) response modality transfer (3) stimulus and
      response modalities transfer task. Training group showed larger improvement than
      the control group in the three transfer dual-task conditions, which suggests that
      training leads to more than specific learning of stimuli/response associations.
      Attentional costs analyses showed that training led to improved dual-task cost,
      only in conditions that involved new stimuli or response modalities, but not
      both. Moreover, training did not lead to a reduced task-set cost in the transfer
      conditions, which suggests some limitations in transfer effects that can be
      expected. Overall, the present study supports the notion that cognitive
      plasticity for attentional control is preserved in late adulthood.

PMID- 22629240
TI  - Your Error's Got me Feeling - How Empathy Relates to the Electrophysiological
      Correlates of Performance Monitoring.
AB  - The error-related and feedback-related negativities (ERN and FRN) represent
      negative event-related potentials associated with the processing of errors and
      (negative) response outcomes. The neuronal source of these components is
      considered to be in the anterior cingulate cortex (ACC). Monitoring one's own
      behavior and the impact it may have on other people or observing other
      individuals perform and receive feedback for their actions may also engage
      empathy-related processes. Empathy is conceived of as a multifaceted construct
      involving both cognitive and affective components, partly also supported by the
      ACC. The present mini-review aims to summarize the sparse database linking the
      electrophysiological correlates of performance monitoring to empathy. While most
      studies so far provide largely indirect evidence for such an association - e.g.,
      by pointing toward altered ERN/FRN signaling in populations characterized by
      deviations in empathic responding - fewer investigations establish more explicit
      links between the two concepts. The relationship between state and, less
      consistently, trait measures of empathy and action monitoring might be more
      pronounced for observational than for active participation.

PMID- 22629241
TI  - Frontoparietal theta activity supports behavioral decisions in movement-target
      selection.
AB  - There is recent EEG evidence describing task-related changes of theta power in
      spatial attention and reaching/pointing tasks. Here, we aim to better
      characterize this theta activity and determine whether it is associated with
      visuospatial memory or with visuospatial selection functions of the
      frontoparietal cortex. We recorded EEG from 20 participants during a movement
      precuing task with center-out joystick movements. Precues displayed 1, 2, or 4
      potential targets and were followed (stimulus onset asynchrony 1.2 s) by a
      central response cue indicating the movement-target. Remembering the precued
      target location(s) was mandatory in one and optional in a second version of the
      task. Analyses evaluated two slow brain potentials (CNV, contingent negative
      variation and CDA, contralateral delay activity) and task-related power changes.
      Results showed a differential modulation of frontal CNV and parietal CDA,
      consistent with earlier described set-size effects on motor preparation and
      visual short-term memory. Short-lived phases of theta event-related
      synchronization (ERS) were found 150-500 ms after precue and response cue
      presentation, exhibiting parietal and frontal maxima. The increase of
      frontoparietal theta power following response cue presentation was strongly
      modulated by target load, i.e., absent for 1-target (when the movement-target
      could be selected in advance), contrasting with a robust 20-50% ERS response in 2
      and 4-target conditions. The scalp distribution, the timing, and the modulation
      by set-size suggest a role of theta activity in movement-target selection. The
      results support a recently proposed view of theta as emerging around behavioral
      decision points, linked to the evaluation of choice-relevant information.

PMID- 22629243
TI  - In vivo vs. ex vivo Magnetic Resonance Imaging In Mice.

PMID- 22629242
TI  - The hippocampus and spatial constraints on mental imagery.
AB  - We review a model of imagery and memory retrieval based on allocentric spatial
      representation by place cells and boundary vector cells (BVCs) in the medial
      temporal lobe, and their translation into egocentric images in retrosplenial and
      parietal areas. In this model, the activity of place cells constrain the contents
      of imagery and retrieval to be coherent and consistent with the subject occupying
      a single location, while the activity of head-direction cells along Papez's
      circuit determine the viewpoint direction for which the egocentric image is
      generated. An extension of this model is discussed in which a role for grid cells
      in dynamic updating of representations (mental navigation) is included. We also
      discuss the extension of this model to implement a version of the dual
      representation theory of post-traumatic stress disorder (PTSD) in which PTSD
      arises from an imbalance between weak allocentric hippocampal-mediated contextual
      representations and strong affective/sensory representations. The implications of
      these models for behavioral, neuropsychological, and neuroimaging data in humans
      are explored.

PMID- 22629244
TI  - The budget impact of oral nutritional supplements for disease related
      malnutrition in elderly in the community setting.
AB  - A health economic analysis was performed to assess the economic impact on the
      national health care budget of using oral nutritional supplements (ONS), being a
      food for special medical purposes also known as medical nutrition, for the
      treatment of disease related malnutrition (DRM) in the community in the
      Netherlands. An economic model was developed to calculate the budget impact of
      using ONS in community dwelling elderly (>5 years) with DRM in the Netherlands.
      The model reflects the costs of DRM and the cost reductions resulting from
      improvement in DRM due to treatment with ONS. Using ONS for the treatment of DRM
      in community dwelling elderly, leads to a total annual cost savings of ? 13
      million (18.9% savings), when all eligible patients are treated. The additional
      costs of ONS (? 57 million) are more than balanced by a reduction of other health
      care costs, e.g., re-/hospitalization (? 70 million). Sensitivity analyses were
      performed on all parameters, including duration of treatment with ONS and the
      prevalence of DRM. This budget impact analysis shows that the use of ONS for
      treatment of DRM in elderly patients in the community may lead to cost savings in
      the Netherlands.

PMID- 22629245
TI  - Developmental Changes in the ECG of a Hamster Model of Muscular Dystrophy and
      Heart Failure.
AB  - Aberrant autonomic signaling is being increasingly recognized as an important
      symptom in neuromuscular disorders. The delta-sarcoglycan-deficient BIO TO-2
      hamster is recognized as a good model for studying mechanistic pathways and
      sequelae in muscular dystrophy and heart failure, including autonomic nervous
      system (ANS) dysfunction. Recent studies using the TO-2 hamster model have
      provided promising preclinical results demonstrating the efficacy of gene therapy
      to treat skeletal muscle weakness and heart failure. Methods to accelerate
      preclinical testing of gene therapy and new drugs for neuromuscular diseases are
      urgently needed. The purpose of this investigation was to demonstrate a rapid non
      invasive screen for characterizing the ANS imbalance in dystrophic TO-2 hamsters.
      Electrocardiograms were recorded non-invasively in conscious ~9-month old TO-2
      hamsters (n = 10) and non-myopathic F1B control hamsters (n = 10). Heart rate was
      higher in TO-2 hamsters than controls (453 +/- 12 bpm vs. 311 +/- 25 bpm, P <
      0.01). Time domain heart rate variability, an index of parasympathetic tone, was
      lower in TO-2 hamsters (12.2 +/- 3.7 bpm vs. 38.2 +/- 6.8, P < 0.05), as was the
      coefficient of variance of the RR interval (2.8 +/- 0.9% vs. 16.2 +/- 3.4%, P <
      0.05) compared to control hamsters. Power spectral analysis demonstrated reduced
      high frequency and low frequency contributions, indicating autonomic imbalance
      with increased sympathetic tone and decreased parasympathetic tone in dystrophic
      TO-2 hamsters. Similar observations in newborn hamsters indicate autonomic
      nervous dysfunction may occur quite early in life in neuromuscular diseases. Our
      findings of autonomic abnormalities in newborn hamsters with a mutation in the
      delta-sarcoglycan gene suggest approaches to correct modulation of the heart rate
      as prevention or therapy for muscular dystrophies.

PMID- 22629247
TI  - The dynamics of group formation among leeches.
AB  - Leeches exploring a new environment continuously meet each other and merge in
      temporary groups. After 2-3 h, leeches become attracted to each other eventually
      forming a large and stable group. When their number is reduced, leeches remain
      solitary, behaving independently. Group formation is facilitated by body
      injection of serotonin (5-HT) and the level of endogenous 5-HT is elevated in
      leeches forming a large group. In contrast, intravenous injection of 5-HT
      antagonists prevented injected leeches from joining a large group of
      conspecifics. When sensilla near the head were ablated or the supraesophageal
      ganglion disconnected, leeches remained solitary, but explored the environment
      swimming and crawling. These results suggest that group formation is initiated by
      a release of 5-HT triggered by sensilla stimulation and its dynamics can be
      explained by the establishment of a reinforcement dynamics, as observed during
      human group formation. As 5-HT affects social interactions also in humans, group
      formation in leeches and humans share a similar dynamics and hormonal control.

PMID- 22629246
TI  - Transport and metabolism at blood-brain interfaces and in neural cells: relevance
      to bilirubin-induced encephalopathy.
AB  - Bilirubin, the end-product of heme catabolism, circulates in non-pathological
      plasma mostly as a protein-bound species. When bilirubin concentration builds up,
      the free fraction of the molecule increases. Unbound bilirubin then diffuses
      across blood-brain interfaces (BBIs) into the brain, where it accumulates and
      exerts neurotoxic effects. In this classical view of bilirubin neurotoxicity,
      BBIs act merely as structural barriers impeding the penetration of the pigment
      bound carrier protein, and neural cells are considered as passive targets of its
      toxicity. Yet, the role of BBIs in the occurrence of bilirubin encephalopathy
      appears more complex than being simple barriers to the diffusion of bilirubin,
      and neural cells such as astrocytes and neurons can play an active role in
      controlling the balance between the neuroprotective and neurotoxic effects of
      bilirubin. This article reviews the emerging in vivo and in vitro data showing
      that transport and metabolic detoxification mechanisms at the blood-brain and
      blood-cerebrospinal fluid barriers may modulate bilirubin flux across both
      cellular interfaces, and that these protective functions can be affected in
      chronic unconjugated hyperbilirubinemia. Then the in vivo and in vitro arguments
      in favor of the physiological antioxidant function of intracerebral bilirubin are
      presented, as well as the potential role of transporters such as ABCC1 and
      metabolizing enzymes such as cytochromes P-450 in setting the cerebral cell- and
      structure-specific toxicity of bilirubin following hyperbilirubinemia. The
      relevance of these data to the pathophysiology of bilirubin-induced neurological
      diseases is discussed.

PMID- 22629248
TI  - The yeast retrograde response as a model of intracellular signaling of
      mitochondrial dysfunction.
AB  - Mitochondrial dysfunction activates intracellular signaling pathways that impact
      yeast longevity, and the best known of these pathways is the retrograde response.
      More recently, similar responses have been discerned in other systems, from
      invertebrates to human cells. However, the identity of the signal transducers is
      either unknown or apparently diverse, contrasting with the well-established
      signaling module of the yeast retrograde response. On the other hand, it has
      become equally clear that several other pathways and processes interact with the
      retrograde response, embedding it in a network responsive to a variety of
      cellular states. An examination of this network supports the notion that the
      master regulator NFkappaB aggregated a variety of mitochondria-related cellular
      responses at some point in evolution and has become the retrograde transcription
      factor. This has significant consequences for how we view some of the deficits
      associated with aging, such as inflammation. The support for NFkappaB as the
      retrograde response transcription factor is not only based on functional
      analyses. It is bolstered by the fact that NFkappaB can regulate Myc-Max, which
      is activated in human cells with dysfunctional mitochondria and impacts cellular
      metabolism. Myc-Max is homologous to the yeast retrograde response transcription
      factor Rtg1-Rtg3. Further research will be needed to disentangle the pro-aging
      from the anti-aging effects of NFkappaB. Interestingly, this is also a challenge
      for the complete understanding of the yeast retrograde response.

PMID- 22629249
TI  - Effects of physical activity and inactivity on muscle fatigue.
AB  - The aim of this review was to examine the mechanisms by which physical activity
      and inactivity modify muscle fatigue. It is well known that acute or chronic
      increases in physical activity result in structural, metabolic, hormonal, neural,
      and molecular adaptations that increase the level of force or power that can be
      sustained by a muscle. These adaptations depend on the type, intensity, and
      volume of the exercise stimulus, but recent studies have highlighted the role of
      high intensity, short-duration exercise as a time-efficient method to achieve
      both anaerobic and aerobic/endurance type adaptations. The factors that determine
      the fatigue profile of a muscle during intense exercise include muscle fiber
      composition, neuromuscular characteristics, high energy metabolite stores,
      buffering capacity, ionic regulation, capillarization, and mitochondrial density.
      Muscle fiber-type transformation during exercise training is usually toward the
      intermediate type IIA at the expense of both type I and IIx myosin heavy-chain
      isoforms. High-intensity training results in increases of both glycolytic and
      oxidative enzymes, muscle capillarization, improved phosphocreatine resynthesis
      and regulation of K(+), H(+), and lactate ions. Decreases of the habitual
      activity level due to injury or sedentary lifestyle result in partial or even
      compete reversal of the adaptations due to previous training, manifested by
      reductions in fiber cross-sectional area, decreased oxidative capacity, and
      capillarization. Complete immobilization due to injury results in markedly
      decreased force output and fatigue resistance. Muscle unloading reduces
      electromyographic activity and causes muscle atrophy and significant decreases in
      capillarization and oxidative enzymes activity. The last part of the review
      discusses the beneficial effects of intermittent high-intensity exercise training
      in patients with different health conditions to demonstrate the powerful effect
      of exercise on health and well being.

PMID- 22629251
TI  - Typical and atypical antipsychotic drugs increase extracellular histamine levels
      in the rat medial prefrontal cortex: contribution of histamine h(1) receptor
      blockade.
AB  - Atypical antipsychotics such as clozapine and olanzapine have been shown to
      enhance histamine turnover and this effect has been hypothesized to contribute to
      their improved therapeutic profile compared to typical antipsychotics. In the
      present study, we examined the effects of antipsychotic drugs on histamine (HA)
      efflux in the mPFC of the rat by means of in vivo microdialysis and sought to
      differentiate the receptor mechanisms which underlie such effects. Olanzapine and
      clozapine increased mPFC HA efflux in a dose related manner. Increased HA efflux
      was also observed after quetiapine, chlorpromazine, and perphenazine treatment.
      We found no effect of the selective 5-HT(2A) antagonist MDL100907, 5-HT(2c)
      antagonist SB242084, or the 5-HT(6) antagonist Ro 04-6790 on mPFC HA efflux. HA
      efflux was increased following treatment with selective H(1) receptor antagonists
      pyrilamine, diphenhydramine, and triprolidine, the H(3) receptor antagonist
      ciproxifan and the mixed 5-HT(2A)/H(1) receptor antagonist ketanserin. The
      potential novel antipsychotic drug FMPD, which has a lower affinity at H(1)
      receptors than olanzapine, did not affect HA efflux. Similarly, other
      antipsychotics with lower H(1) receptor affinity (risperidone, aripiprazole, and
      haloperidol) were also without effect on HA efflux. Finally, HA efflux after
      antipsychotic treatment was significantly correlated with affinity at H(1)
      receptors whereas nine other receptors, including 5-HT(2A), were not. These
      results demonstrate that both typical and atypical antipsychotics increase mPFC
      histamine efflux and this effect may be mediated via antagonism of histamine H(1)
      receptors.

PMID- 22629250
TI  - Function and Regulation of Lipid Biology in Caenorhabditis elegans Aging.
AB  - Rapidly expanding aging populations and a concomitant increase in the prevalence
      of age-related diseases are global health problems today. Over the past three
      decades, a large body of work has led to the identification of genes and
      regulatory networks that affect longevity and health span, often benefiting from
      the tremendous power of genetics in vertebrate and invertebrate model organisms.
      Interestingly, many of these factors appear linked to lipids, important molecules
      that participate in cellular signaling, energy metabolism, and structural
      compartmentalization. Despite the putative link between lipids and longevity, the
      role of lipids in aging remains poorly understood. Emerging data from the model
      organism Caenorhabditis elegans suggest that lipid composition may change during
      aging, as several pathways that influence aging also regulate lipid metabolism
      enzymes; moreover, some of these enzymes apparently play key roles in the
      pathways that affect the rate of aging. By understanding how lipid biology is
      regulated during C. elegans aging, and how it impacts molecular, cellular, and
      organismal function, we may gain insight into novel ways to delay aging using
      genetic or pharmacological interventions. In the present review we discuss recent
      insights into the roles of lipids in C. elegans aging, including regulatory roles
      played by lipids themselves, the regulation of lipid metabolic enzymes, and the
      roles of lipid metabolism genes in the pathways that affect aging.

PMID- 22629252
TI  - Training of tonal similarity ratings in non-musicians: a "rapid learning"
      approach.
AB  - Although cognitive music psychology has a long tradition of expert-novice
      comparisons, experimental training studies are rare. Studies on the learning
      progress of trained novices in hearing harmonic relationships are still largely
      lacking. This paper presents a simple training concept using the example of
      tone/triad similarity ratings, demonstrating the gradual progress of non
      musicians compared to musical experts: In a feedback-based "rapid learning"
      paradigm, participants had to decide for single tones and chords whether paired
      sounds matched each other well. Before and after the training sessions, they
      provided similarity judgments for a complete set of sound pairs. From these
      similarity matrices, individual relational sound maps, intended to display mental
      representations, were calculated by means of non-metric multidimensional scaling
      (NMDS), and were compared to an expert model through procrustean transformation.
      Approximately half of the novices showed substantial learning success, with some
      participants even reaching the level of professional musicians. Results speak for
      a fundamental ability to quickly train an understanding of harmony, show inter
      individual differences in learning success, and demonstrate the suitability of
      the scaling method used for learning research in music and other domains. Results
      are discussed in the context of the "giftedness" debate.

PMID- 22629253
TI  - Frontoparietal Connectivity and Hierarchical Structure of the Brain's Functional
      Network during Sleep.
AB  - Frontal and parietal regions are associated with some of the most complex
      cognitive functions, and several frontoparietal resting-state networks can be
      observed in wakefulness. We used functional magnetic resonance imaging data
      acquired in polysomnographically validated wakefulness, light sleep, and slow
      wave sleep to examine the hierarchical structure of a low-frequency functional
      brain network, and to examine whether frontoparietal connectivity would
      disintegrate in sleep. Whole-brain analyses with hierarchical cluster analysis on
      predefined atlases were performed, as well as regression of inferior parietal
      lobules (IPL) seeds against all voxels in the brain, and an evaluation of the
      integrity of voxel time-courses in subcortical regions-of-interest. We observed
      that frontoparietal functional connectivity disintegrated in sleep stage 1 and
      was absent in deeper sleep stages. Slow-wave sleep was characterized by strong
      hierarchical clustering of local submodules. Frontoparietal connectivity between
      IPL and superior medial and right frontal gyrus was lower in sleep stages than in
      wakefulness. Moreover, thalamus voxels showed maintained integrity in sleep stage
      1, making intrathalamic desynchronization an unlikely source of reduced
      thalamocortical connectivity in this sleep stage. Our data suggest a transition
      from a globally integrated functional brain network in wakefulness to a
      disintegrated network consisting of local submodules in slow-wave sleep, in which
      frontoparietal inter-modular nodes may play a role, possibly in combination with
      the thalamus.

PMID- 22629254
TI  - Cognition in rapid eye movement sleep behavior disorder.
AB  - Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia
      characterized by excessive muscle activity and undesirable motor events during
      REM sleep. RBD occurs in approximately 0.5% of the general population, with a
      higher prevalence in older men. RBD is a frequent feature of dementia with Lewy
      bodies (DLB), but is only rarely reported in Alzheimer's disease. RBD is also a
      risk factor for alpha-synuclein-related diseases, such as DLB, Parkinson's
      disease (PD), and multiple system atrophy. Therefore, RBD has major implications
      for the diagnosis and treatment of neurodegenerative disorders and for
      understanding specific neurodegeneration patterns. Several markers of
      neurodegeneration have been identified in RBD, including cognitive impairments
      such as deficits in attention, executive functions, learning capacities, and
      visuospatial abilities. Approximately 50% of RBD patients present mild cognitive
      impairment. Moreover, RBD is also associated with cognitive decline in PD.

PMID- 22629255
TI  - Therapeutic potential of semi-mature dendritic cells for tolerance induction.
AB  - Dendritic cells (DCs) are major players in the control of adaptive tolerance and
      immunity. Therefore, their specific generation and adoptive transfer into
      patients or their in vivo targeting is attractive for clinical applications.
      While injections of mature immunogenic DCs are tested in clinical trials,
      tolerogenic DCs still are awaiting this step. Besides the tolerogenic potential
      of immature DCs, also semi-mature DCs can show tolerogenic activity but both
      types also bear unfavorable features. Optimal tolerogenic DCs, their molecular
      tool bar, and their use for specific diseases still have to be defined. Here, the
      usefulness of in vitro generated and adoptively transferred semi-mature DCs for
      tolerance induction is outlined. The in vivo targeting of semi-mature DCs as
      represented by steady state migratory DCs are discussed for treatment of
      autoimmune diseases and allergies. First clinical trials with transcutaneous
      allergen application may point to their therapeutic use in the future.

PMID- 22629256
TI  - On the interactions between mesenchymal stem cells and regulatory T cells for
      immunomodulation in transplantation.
AB  - Experimental studies have established the use of mesenchymal stem cells (MSC) as
      a candidate immunosuppressive therapy. MSC exert their immunomodulatory function
      through the inhibition of CD4(+) and CD8(+) T cell proliferation. It is unknown
      whether MSC impair the immunosuppressive function of regulatory T cells (Treg).
      In vitro and in vivo studies suggest that MSC mediate their immunomodulatory
      effects through the induction of Treg. In this review we will focus on the
      interactions between MSC and Treg, and evaluate the consequences of these
      cellular interplays for prospective MSC immunotherapy in organ transplantation.

PMID- 22629257
TI  - Understanding Plant Cellulose Synthases through a Comprehensive Investigation of
      the Cellulose Synthase Family Sequences.
AB  - The development of cellulose as an organizing structure in the plant cell wall
      was a key event in both the initial colonization and the subsequent domination of
      the terrestrial ecosystem by vascular plants. A wealth of experimental data has
      demonstrated the complicated genetic interactions required to form the large
      synthetic complex that synthesizes cellulose. However, these results are lacking
      an extensive analysis of the evolution, specialization, and regulation of the
      proteins that compose this complex. Here we perform an in-depth analysis of the
      sequences in the cellulose synthase (CesA) family. We investigate the phylogeny
      of the CesA family, with emphasis on evolutionary specialization. We define
      specialized clades and identify the class-specific regions within the CesA
      sequence that may explain this specialization. We investigate changes in
      regulation of CesAs by looking at the conservation of proposed phosphorylation
      sites. We investigate the conservation of sites where mutations have been
      documented that impair CesA function, and compare these sites to those observed
      in the closest cellulose synthase-like (Csl) families to better understand what
      regions may separate the CesAs from other Csls. Finally we identify two positions
      with strong conservation of the aromatic trait, but lacking conservation of amino
      acid identity, which may represent residues important for positioning the sugar
      substrate for catalysis. These analyses provide useful tools for understanding
      characterized mutations and post-translational modifications, and for informing
      further experiments to probe CesA assembly, regulation, and function through site
      directed mutagenesis or domain swapping experiments.

PMID- 22629258
TI  - Plant developmental biology in the post-genomic era.

PMID- 22629259
TI  - Sequence Variation and Expression Analysis of Seed Dormancy- and Germination
      Associated ABA- and GA-Related Genes in Rice Cultivars.
AB  - Abscisic acid (ABA) and Gibberellic acid (GA) play key roles in regulating seed
      dormancy and germination. First, when examining germination of different rice
      cultivars, we found that their germination timing and dormancy status are rather
      distinct, coupled with different GA/ABA ratio. Second, we studied genomic
      sequences of ABA and GA dormancy- and germination-associated genes in rice and
      discovered single nucleotide polymorphisms and insertions/deletions (Indels) in
      both coding and regulatory sequences. We aligned all these variations to the
      genome assemblies of 9311 and PA64s and demonstrated their relevance to seed
      dormancy both quantitatively and qualitatively based on gene expression data.
      Third, we surveyed and compared differentially expressed genes in dry seeds
      between 9311 and PA64s to show that these differentially expressed genes may play
      roles in seed dormancy and germination.

PMID- 22629261
TI  - Metabolite Signature during Short-Day Induced Growth Cessation in Populus.
AB  - The photoperiod is an important environmental signal for plants, and influences a
      wide range of physiological processes. For woody species in northern latitudes,
      cessation of growth is induced by short photoperiods. In many plant species,
      short photoperiods stop elongational growth after a few weeks. It is known that
      plant daylength detection is mediated by Phytochrome A (PHYA) in the woody hybrid
      aspen species. However, the mechanism of dormancy involving primary metabolism
      remains unclear. We studied changes in metabolite profiles in hybrid aspen leaves
      (young, middle, and mature leaves) during short-day-induced growth cessation,
      using a combination of gas chromatography-time-of-flight mass spectrometry, and
      multivariate projection methods. Our results indicate that the metabolite
      profiles in mature source leaves rapidly change when the photoperiod changes. In
      contrast, the differences in young sink leaves grown under long and short-day
      conditions are less distinct. We found short daylength induced growth cessation
      in aspen was associated with rapid changes in the distribution and levels of
      diverse primary metabolites. In addition, we conducted metabolite profiling of
      leaves of PHYA overexpressor (PHYAOX) and those of the control to find the
      discriminative metabolites between PHYAOX and the control under the short-day
      conditions. The metabolite changes observed in PHYAOX leaves, together with those
      in the source leaves, identified possible candidates for the metabolite signature
      (e.g., 2-oxo-glutarate, spermidine, putrescine, 4-amino-butyrate, and tryptophan)
      during short-day-induced growth cessation in aspen leaves.

PMID- 22629260
TI  - Homologs of breast cancer genes in plants.
AB  - Since the initial discovery of genes involved in hereditary breast cancer in
      humans, a vast wealth of information has been published. Breast cancer proteins
      were shown to work as tumor suppressors primarily through their involvement in
      DNA-damage repair. Surprisingly, homologs of these genes can be found in plant
      genomes, as well. Here, we want to give an overview of the identification and
      characterization of the biological roles of these proteins, in plants. In
      addition to the conservation of their function in DNA repair, new plant-specific
      characteristics have been revealed. BRCA1 is required for the efficient repair of
      double strand breaks (DSB) by homologous recombination in somatic cells of the
      model plant Arabidopsis thaliana. Bioinformatic analysis indicates that, whereas
      most homologs of key components of the different mammalian BRCA1 complexes are
      present in plant genomes, homologs of most factors involved in the recruitment of
      BRCA1 to the DSB cannot be identified. Thus, it is not clear at the moment
      whether differences exist between plants and animals at this important step. The
      most conserved region of BRCA1 and BARD1 homologs in plants is a PHD domain which
      is absent in mammals and which, in AtBARD1, might be involved in the
      transcriptional regulation of plant development. The presence of a plant-specific
      domain prompted us to reevaluate the current model for the evolution of BRCA1
      homologs and to suggest a new hypothesis, in which we postulate that plant BRCA1
      and BARD1 have one common predecessor that gained a PHD domain before
      duplication. Furthermore, work in Arabidopsis demonstrates that - as in animals -
      BRCA2 homologs are important for meiotic DNA recombination. Surprisingly, recent
      research has revealed that AtBRCA2 also has an important role in systemic
      acquired resistance. In Arabidopsis, BRCA2 is involved in the transcriptional
      regulation of pathogenesis-related (PR) genes via its interaction with the strand
      exchange protein RAD51.

PMID- 22629262
TI  - Grand Challenge: Accelerating Discovery through Technology Development.

PMID- 22629263
TI  - Bringing the dead compartment of a plant cell to life: a novel imaging technique
      resurrects the dynamic nature of the apoplast.

PMID- 22629264
TI  - Ultra performance liquid chromatography and high resolution mass spectrometry for
      the analysis of plant lipids.
AB  - Holistic analysis of lipids is becoming increasingly popular in the life
      sciences. Recently, several interesting, mass spectrometry-based studies have
      been conducted, especially in plant biology. However, while great advancements
      have been made we are still far from detecting all the lipids species in an
      organism. In this study we developed an ultra performance liquid chromatography
      based method using a high resolution, accurate mass, mass spectrometer for the
      comprehensive profiling of more than 260 polar and non-polar Arabidopsis thaliana
      leaf lipids. The method is fully compatible to the commonly used lipid extraction
      protocols and provides a viable alternative to the commonly used direct infusion
      based shotgun lipidomics approaches. The whole process is described in detail and
      compared to alternative lipidomic approaches. Next to the developed method we
      also introduce an in-house developed database search software (GoBioSpace), which
      allows one to perform targeted or un-targeted lipidomic and metabolomic analysis
      on mass spectrometric data of every kind.

PMID- 22629265
TI  - How do sugars regulate plant growth?

PMID- 22629267
TI  - Preferential repair of the transcribed DNA strand in plants.
AB  - UV-induced pyrimidine dimers block the progression of both DNA and RNA
      polymerases. In order to reduce the disruptive effect of these lesions on gene
      expression, bacteria, yeasts, and animals preferentially repair the transcribed
      strand of actively expressed genes, essentially employing the stalled polymerase
      as a detector for bulky lesions. It has been assumed, but not demonstrated, that
      this prioritization of repair also occurs in plants. Here we demonstrate that in
      the constitutively expressed gene encoding the RNA polymerase II large subunit
      cyclobutane pyrimidine dimers are removed from the transcribed strand more
      rapidly than from the non-transcribed strand.

PMID- 22629268
TI  - RNA regulatory elements and polyadenylation in plants.
AB  - Alternative poly(A) site choice (also known as alternative polyadenylation, or
      APA) has the potential to affect gene expression in qualitative and quantitative
      ways. APA may affect as many as 82% of all expressed genes in a plant. The
      consequences of APA include the generation of transcripts with differing 3'-UTRs
      (and thus differing regulatory potential) and of transcripts with differing
      protein-coding potential. Genome-wide studies of possible APA suggest a linkage
      with pre-mRNA splicing, and indicate a coincidence of and perhaps cooperation
      between RNA regulatory elements that affect splicing efficiency and the
      recognition of novel intronic poly(A) sites. These studies also raise the
      possibility of the existence of a novel class of polyadenylation-related cis
      elements that are distinct from the well-characterized plant polyadenylation
      signal. Many potential APA events, however, have not been associated with
      identifiable cis elements. The present state of the field reveals a broad scope
      of APA, and also numerous opportunities for research into mechanisms that govern
      both choice and regulation of poly(A) sites in plants.

PMID- 22629269
TI  - Phylogenetic Analysis of the Thylakoid ATP/ADP Carrier Reveals New Insights into
      Its Function Restricted to Green Plants.
AB  - ATP is the common energy currency of cellular metabolism in all living organisms.
      Most of them synthesize ATP in the cytosol or on the mitochondrial inner
      membrane, whereas land plants, algae, and cyanobacteria also produce it on the
      thylakoid membrane during the light-dependent reactions of photosynthesis. From
      the site of synthesis, ATP is transported to the site of utilization via
      intracellular membrane transporters. One major type of ATP transporters is
      represented by the mitochondrial ADP/ATP carrier family. Here we review a
      recently characterized member, namely the thylakoid ATP/ADP carrier from
      Arabidopsis thaliana (AtTAAC). Thus far, no orthologs of this carrier have been
      characterized in other organisms, although similar sequences can be recognized in
      many sequenced genomes. Protein Sequence database searches and phylogenetic
      analyses indicate the absence of TAAC in cyanobacteria and its appearance early
      in the evolution of photosynthetic eukaryotes. The TAAC clade is composed of
      carriers found in land plants and some green algae, but no proteins from other
      photosynthetic taxa, such as red algae, brown algae, and diatoms. This implies
      that TAAC-like sequences arose only once before the divergence of green algae and
      land plants. Based on these findings, it is proposed that TAAC may have evolved
      in response to the need of a new activity in higher photosynthetic eukaryotes.
      This activity may provide the energy to drive reactions during biogenesis and
      turnover of photosynthetic complexes, which are heterogeneously distributed in a
      thylakoid membrane system composed of appressed and non-appressed regions.

PMID- 22629266
TI  - The Plastid Outer Envelope - A Highly Dynamic Interface between Plastid and
      Cytoplasm.
AB  - Plastids are the defining organelles of all photosynthetic eukaryotes. They are
      the site of photosynthesis and of a large number of other essential metabolic
      pathways, such as fatty acid and amino acid biosyntheses, sulfur and nitrogen
      assimilation, and aromatic and terpenoid compound production, to mention only a
      few examples. The metabolism of plastids is heavily intertwined and connected
      with that of the surrounding cytosol, thus causing massive traffic of metabolic
      precursors, intermediates, and products. Two layers of biological membranes that
      are called the inner (IE) and the outer (OE) plastid envelope membranes bound the
      plastids of Archaeplastida. While the IE is generally accepted as the osmo
      regulatory barrier between cytosol and stroma, the OE was considered to represent
      an unspecific molecular sieve, permeable for molecules of up to 10 kDa. However,
      after the discovery of small substrate specific pores in the OE, this view has
      come under scrutiny. In addition to controlling metabolic fluxes between plastid
      and cytosol, the OE is also crucial for protein import into the chloroplast. It
      contains the receptors and translocation channel of the TOC complex that is
      required for the canonical post-translational import of nuclear-encoded, plastid
      targeted proteins. Further, the OE is a metabolically active compartment of the
      chloroplast, being involved in, e.g., fatty acid metabolism and membrane lipid
      production. Also, recent findings hint on the OE as a defense platform against
      several biotic and abiotic stress conditions, such as cold acclimation, freezing
      tolerance, and phosphate deprivation. Moreover, dynamic non-covalent interactions
      between the OE and the endomembrane system are thought to play important roles in
      lipid and non-canonical protein trafficking between plastid and endoplasmic
      reticulum. While proteomics and bioinformatics has provided us with comprehensive
      but still incomplete information on proteins localized in the plastid IE, the
      stroma, and the thylakoids, our knowledge of the protein composition of the
      plastid OE is far from complete. In this article, we report on the recent
      progress in discovering novel OE proteins to draw a conclusive picture of the OE.
      A "parts list" of the plastid OE will be presented, using data generated by
      proteomics of plastids isolated from various plant sources.

PMID- 22629270
TI  - Allele mining in barley genetic resources reveals genes of race-non-specific
      powdery mildew resistance.
AB  - Race-non-specific, or quantitative, pathogen resistance is of high importance to
      plant breeders due to its expected durability. However, it is usually controlled
      by multiple quantitative trait loci (QTL) and therefore difficult to handle in
      practice. Knowing the genes that underlie race-non-specific resistance (NR) would
      allow its exploitation in a more targeted manner. Here, we performed an
      association-genetic study in a customized worldwide collection of spring barley
      accessions for candidate genes of race-NR to the powdery mildew fungus Blumeria
      graminis f. sp. hordei (Bgh) and combined data with results from QTL mapping as
      well as functional-genomics approaches. This led to the identification of 11
      associated genes with converging evidence for an important role in race-NR in the
      presence of the Mlo gene for basal susceptibility. Outstanding in this respect
      was the gene encoding the transcription factor WRKY2. The results suggest that
      unlocking plant genetic resources and integrating functional-genomic with genetic
      approaches can accelerate the discovery of genes underlying race-NR in barley and
      other crop plants.

PMID- 22629271
TI  - Functional Diversity of Photosynthetic Light Use of 16 Vascular Epiphyte Species
      Under Fluctuating Irradiance in the Canopy of a Giant Virola michelii
      (Myristicaceae) Tree in the Tropical Lowland Forest of French Guyana.
AB  - Here we present the first study, in which a large number of different vascular
      epiphyte species were measured for their photosynthetic performance in the
      natural environment of their phorophyte in the lowland rainforest of French
      Guyana. More than 70 epiphyte species covered the host tree in a dense cover. Of
      these, the photosynthesis of 16 abundant species was analyzed intensely over
      several months. Moreover, the light environment was characterized with newly
      developed light sensors that recorded continuously and with high temporal
      resolution light intensity next to the epiphytes. Light intensity was highly
      fluctuating and showed great site specific spatio-temporal variations of
      photosynthetic photon flux. Using a novel computer routine we quantified the
      integrated light intensity the epiphytes were exposed to in a 3 h window and we
      related this light intensity to measurements of the actual photosynthetic status.
      It could be shown that the photosynthetic apparatus of the epiphytes was well
      adapted to the quickly changing light conditions. Some of the epiphytes were
      chronically photoinhibited at predawn and significant acute photoinhibition,
      expressed by a reduction of potential quantum efficiency (F(v)/F(m))(30'), was
      observed during the day. By correlating (F(v)/F(m))(30') to the integrated and
      weighted light intensity perceived during the previous 3 h, it became clear that
      acute photoinhibition was related to light environment prior to the measurements.
      Additionally photosynthetic performance was not determined by rain events, with
      the exception of an Aechmea species. This holds true for all the other 15 species
      of this study and we thus conclude that actual photosynthesis of these tropical
      epiphytes was determined by the specific and fluctuating light conditions of
      their microhabitat and cannot be simply attributed to light-adapted ancestors.

PMID- 22629272
TI  - Evolutionary relationships and functional diversity of plant sulfate
      transporters.
AB  - Sulfate is an essential nutrient cycled in nature. Ion transporters that
      specifically facilitate the transport of sulfate across the membranes are found
      ubiquitously in living organisms. The phylogenetic analysis of known sulfate
      transporters and their homologous proteins from eukaryotic organisms indicate two
      evolutionarily distinct groups of sulfate transport systems. One major group
      named Tribe 1 represents yeast and fungal SUL, plant SULTR, and animal SLC26
      families. The evolutionary origin of SULTR family members in land plants and
      green algae is suggested to be common with yeast and fungal SUL and animal anion
      exchangers (SLC26). The lineage of plant SULTR family is expanded into four
      subfamilies (SULTR1-SULTR4) in land plant species. By contrast, the putative
      SULTR homologs from Chlorophyte green algae are in two separate lineages; one
      with the subfamily of plant tonoplast-localized sulfate transporters (SULTR4),
      and the other diverged before the appearance of lineages for SUL, SULTR, and
      SLC26. There also was a group of yet undefined members of putative sulfate
      transporters in yeast and fungi divergent from these major lineages in Tribe 1.
      The other distinct group is Tribe 2, primarily composed of animal sodium
      dependent sulfate/carboxylate transporters (SLC13) and plant tonoplast-localized
      dicarboxylate transporters (TDT). The putative sulfur-sensing protein (SAC1) and
      SAC1-like transporters (SLT) of Chlorophyte green algae, bryophyte, and lycophyte
      show low degrees of sequence similarities with SLC13 and TDT. However, the
      phylogenetic relationship between SAC1/SLT and the other two families, SLC13 and
      TDT in Tribe 2, is not clearly supported. In addition, the SAC1/SLT family is
      absent in the angiosperm species analyzed. The present study suggests distinct
      evolutionary trajectories of sulfate transport systems for land plants and green
      algae.

PMID- 22629273
TI  - Evolution of plant p-type ATPases.
AB  - Five organisms having completely sequenced genomes and belonging to all major
      branches of green plants (Viridiplantae) were analyzed with respect to their
      content of P-type ATPases encoding genes. These were the chlorophytes
      Ostreococcus tauri and Chlamydomonas reinhardtii, and the streptophytes
      Physcomitrella patens (a non-vascular moss), Selaginella moellendorffii (a
      primitive vascular plant), and Arabidopsis thaliana (a model flowering plant).
      Each organism contained sequences for all five subfamilies of P-type ATPases.
      Whereas Na(+) and H(+) pumps seem to mutually exclude each other in flowering
      plants and animals, they co-exist in chlorophytes, which show representatives for
      two kinds of Na(+) pumps (P2C and P2D ATPases) as well as a primitive H(+)
      ATPase. Both Na(+) and H(+) pumps also co-exist in the moss P. patens, which has
      a P2D Na(+)-ATPase. In contrast to the primitive H(+)-ATPases in chlorophytes and
      P. patens, the H(+)-ATPases from vascular plants all have a large C-terminal
      regulatory domain as well as a conserved Arg in transmembrane segment 5 that is
      predicted to function as part of a backflow protection mechanism. Together these
      features are predicted to enable H(+) pumps in vascular plants to create large
      electrochemical gradients that can be modulated in response to diverse
      physiological cues. The complete inventory of P-type ATPases in the major
      branches of Viridiplantae is an important starting point for elucidating the
      evolution in plants of these important pumps.

PMID- 22629274
TI  - Social Network: JAZ Protein Interactions Expand Our Knowledge of Jasmonate
      Signaling.
AB  - Members of the family of JASMONATE ZIM-DOMAIN (JAZ) proteins are key regulators
      of the jasmonate (JA) hormonal response. The 12-member family is characterized by
      three conserved domains, an N-terminal domain, a TIFY-containing ZINC-FINGER
      EXPRESSED IN INFLORESCENCE MERISTEM domain, and a C-terminal Jas domain. JAZ
      proteins regulate JA-responsive gene transcription by inhibiting DNA-binding
      transcription factors in the absence of JA. JAZ proteins interact in a hormone
      dependent manner with CORONATINE INSENSITIVE 1 (COI1), the recognition component
      of the E3 ubiquitin ligase, SCF(COI1), resulting in the ubiquitination and
      subsequent degradation of JAZs via the 26S proteasome pathway. Since their
      discovery in 2007, JAZ proteins have been implicated in protein-protein
      interactions with multiple transcription factors. These studies have shed light
      on the mechanism by which JAZs repress transcription, are targeted for
      degradation, modulate the JA signaling response, and participate in crosstalk
      with other hormone signaling pathways. In this review, we will take a close look
      at the recent discoveries made possible by the characterization JAZ protein
      protein interactions.

PMID- 22629275
TI  - Comparative Genomics and Molecular Characterization of the Maize PIN Family
      Proteins.

PMID- 22629276
TI  - Levels of Arabidopsis thaliana Leaf Phosphatidic Acids, Phosphatidylserines, and
      Most Trienoate-Containing Polar Lipid Molecular Species Increase during the Dark
      Period of the Diurnal Cycle.
AB  - Previous work has demonstrated that plant leaf polar lipid fatty acid composition
      varies during the diurnal (dark-light) cycle. Fatty acid synthesis occurs
      primarily during the light, but fatty acid desaturation continues in the absence
      of light, resulting in polyunsaturated fatty acids reaching their highest levels
      toward the end of the dark period. In this work, Arabidopsis thaliana were grown
      at constant (21 degrees C) temperature with 12-h light and 12-h dark periods.
      Collision induced dissociation time-of-flight mass spectrometry (MS) demonstrated
      that 16:3 and 18:3 fatty acid content in membrane lipids of leaves are higher at
      the end of the dark than at the end of the light period, while 16:1, 16:2, 18:0,
      and 18:1 content are higher at the end of the light period. Lipid profiling of
      membrane galactolipids, phospholipids, and lysophospholipids by electrospray
      ionization triple quadrupole MS indicated that the monogalactosyldiacylglycerol,
      phosphatidylglycerol, and phosphatidylcholine classes include molecular species
      whose levels are highest at end of the light period and others that are highest
      at the end of the dark period. The levels of phosphatidic acid (PA) and
      phosphatidylserine classes were higher at the end of the dark period, and
      molecular species within these classes either followed the class pattern or were
      not significantly changed in the diurnal cycle. Phospholipase D (PLD) is a family
      of enzymes that hydrolyzes phospholipids to produce PA. Analysis of several PLD
      mutant lines suggests that PLDzeta2 and possibly PLDalpha1 may contribute to
      diurnal cycling of PA. The polar lipid compositional changes are considered in
      relation to recent data that demonstrate phosphatidylcholine acyl editing.

PMID- 22629277
TI  - Phospholipases and the Network of Auxin Signal Transduction with ABP1 and TIR1 as
      Two Receptors: A Comprehensive and Provocative Model.
AB  - Three types of phospholipases, phospholipase D, secreted phospholipase A(2), and
      patatin-related phospholipase A (pPLA) have functions in auxin signal
      transduction. Potential linkage to auxin receptors ABP1 or TIR1, their rapid
      activation or post-translational activation mechanisms, and downstream functions
      regulated by these phospholipases is reviewed and discussed. Only for pPLA all
      aspects are known at least to some detail. Evidence is gathered that all these
      signal reactions are located in the cytosol and seem to merge on regulation of
      PIN-catalyzed auxin efflux transport proteins. As a consequence, auxin
      concentration in the nucleus is also affected and this regulates the E3 activity
      of this auxin receptor. We showed that ABP1, PIN2, and pPLA, all outside the
      nucleus, have an impact on regulation of auxin-induced genes within 30 min. We
      propose that regulation of PIN protein activities and of auxin efflux transport
      are the means to coordinate ABP1 and TIR1 activity and that no physical contact
      between components of the ABP1-triggered cytosolic pathways and TIR1-triggered
      nuclear pathways of signaling is necessary to perform this.

PMID- 22629278
TI  - Plant Glycosyltransferases Beyond CAZy: A Perspective on DUF Families.
AB  - The carbohydrate active enzyme (CAZy) database is an invaluable resource for
      glycobiology and currently contains 45 glycosyltransferase families that are
      represented in plants. Glycosyltransferases (GTs) have many functions in plants,
      but the majority are likely to be involved in biosynthesis of polysaccharides and
      glycoproteins in the plant cell wall. Bioinformatic approaches and structural
      modeling suggest that a number of protein families in plants include GTs that
      have not yet been identified as such and are therefore not included in CAZy.
      These families include proteins with domain of unknown function (DUF) DUF23,
      DUF246, and DUF266. The evidence for these proteins being GTs and their possible
      roles in cell wall biosynthesis is discussed.

PMID- 22629279
TI  - Plant cell wall integrity maintenance as an essential component of biotic stress
      response mechanisms.
AB  - Plant cell walls provide structural support during development and represent
      together with the cuticle the first line of defense against biotic and abiotic
      stress. In recent years, evidence has accumulated that a dedicated plant cell
      wall integrity (CWI) maintenance mechanism exists. This mechanism monitors and
      maintains functional integrity of the cell wall during different biological
      processes. The available data suggest that it may represent a component of the
      stress response mechanisms underlying biotic and abiotic stress responses, which
      has not been identified previously as a distinct mechanism. Here I will review
      the available evidence regarding the mode of action of the CWI maintenance
      mechanism and discuss its role in the context of biotic plant stress response
      mechanisms.

PMID- 22629280
TI  - The Arabidopsis CstF64-Like RSR1/ESP1 Protein Participates in Glucose Signaling
      and Flowering Time Control.
AB  - Mechanisms for sensing and regulating metabolic processes at the cellular level
      are critical for the general physiology and development of living organisms. In
      higher plants, sugar signaling is crucial for adequate regulation of carbon and
      energy metabolism and affects virtually every aspect of development. Although
      many genes are regulated by sugar levels, little is known on how sugar levels are
      measured by plants. Several components of the sugar signaling network have been
      unraveled and demonstrated to have extensive overlap with hormone signaling
      networks. Here we describe the reduced sugar response1-1 (rsr1-1) mutant as a new
      early flowering mutant that displays decreased sensitivity to abscisic acid. Both
      hexokinase1 (HXK1)-dependent and glucose phosphorylation-independent signaling is
      reduced in rsr1-1. Map-based identification of the affected locus demonstrated
      that rsr1-1 carries a premature stop codon in the gene for a CstF64-like putative
      RNA processing factor, ESP1, which is involved in mRNA 3'-end formation. The
      identification of RSR1/ESP1 as a nuclear protein with a potential threonine
      phosphorylation site may explain the impact of protein phosphorylation cascades
      on sugar-dependent signal transduction. Additionally, RSR1/ESP1 may be a crucial
      factor in linking sugar signaling to the control of flowering time.

PMID- 22629281
TI  - Are epigenetic mechanisms involved in radiation-induced bystander effects?
AB  - The "non-targeted effects" of ionizing radiation including bystander effects and
      genomic instability are unique in that no classic mutagenic event occurs in the
      cell showing the effect. In the case of bystander effects, cells which were not
      in the field affected by the radiation show high levels of mutations, chromosome
      aberrations, and membrane signaling changes leading to what is termed "horizontal
      transmission" of mutations and information which may be damaging while in the
      case of genomic instability, generations of cells derived from an irradiated
      progenitor appear normal but then lethal and non-lethal mutations appear in
      distant progeny. This is known as "vertical transmission." In both situations
      high yields of non-clonal mutations leading to distant occurrence of mutation
      events both in space and time. This precludes a mutator phenotype or other
      conventional explanation and appears to indicate a generalized form of stress
      induced mutagenesis which is well documented in bacteria. This review will
      discuss the phenomenology of what we term "non-targeted effects," and will
      consider to what extent they challenge conventional ideas in genetics and
      epigenetics.

PMID- 22629282
TI  - Systems biology approach to identify gene network signatures for colorectal
      cancer.
AB  - In this work, we integrated prior knowledge from gene signatures and protein
      interactions with gene set enrichment analysis (GSEA), and gene/protein network
      modeling together to identify gene network signatures from gene expression
      microarray data. We demonstrated how to apply this approach into discovering gene
      network signatures for colorectal cancer (CRC) from microarray datasets. First,
      we used GSEA to analyze the microarray data through enriching differential genes
      in different CRC-related gene sets from two publicly available up-to-date gene
      set databases - Molecular Signatures Database (MSigDB) and Gene Signatures
      Database (GeneSigDB). Second, we compared the enriched gene sets through
      enrichment score, false-discovery rate, and nominal p-value. Third, we
      constructed an integrated protein-protein interaction (PPI) network through
      connecting these enriched genes by high-quality interactions from a human
      annotated and predicted protein interaction database, with a confidence score
      labeled for each interaction. Finally, we mapped differential gene expressions
      onto the constructed network to build a comprehensive network model containing
      visualized transcriptome and proteome data. The results show that although MSigDB
      has more CRC-relevant gene sets than GeneSigDB, the integrated PPI network
      connecting the enriched genes from both MSigDB and GeneSigDB can provide a more
      complete view for discovering gene network signatures. We also found several
      important sub-network signatures for CRC, such as TP53 sub-network, PCNA sub
      network, and IL8 sub-network, corresponding to apoptosis, DNA repair, and immune
      response, respectively.

PMID- 22629284
TI  - The Path to microRNA Therapeutics in Psychiatric and Neurodegenerative Disorders.
AB  - The microRNA (miRNA) class of non-coding RNAs exhibit a diverse range of
      regulatory roles in neuronal functions that are conserved from lower vertebrates
      to primates. Disruption of miRNA expression has compellingly been linked to
      pathogenesis in neuropsychiatric and neurodegenerative disorders, such as
      schizophrenia, Alzheimer's disease, and autism. The list of transcript targets
      governed by a single miRNA provide a molecular paradigm applicable for
      therapeutic intervention. Indeed, reports have shown that specific manipulation
      of a miRNA in cell or animal models can significantly alter phenotypes linked
      with neurological disease. Here, we review how a diverse range of biological
      systems, including Drosophila, rodents, and primates such as monkeys and humans,
      can be integrated into the translation of miRNAs as novel clinical targets.

PMID- 22629285
TI  - Genome-environmental risk assessment of cocaine dependence.
AB  - Cocaine-associated biomedical and psychosocial problems are substantial twenty
      first century global burdens of disease. This burden is largely driven by a
      cocaine dependence process that becomes engaged with increasing occasions of
      cocaine product use. For this reason, the development of a risk-prediction model
      for cocaine dependence may be of special value. Ultimately, success in building
      such a risk-prediction model may help promote personalized cocaine dependence
      prediction, prevention, and treatment approaches not presently available. As an
      initial step toward this goal, we conducted a genome-environmental risk
      prediction study for cocaine dependence, simultaneously considering 948,658
      single nucleotide polymorphisms (SNPs), six potentially cocaine-related facets of
      environment, and three personal characteristics. In this study, a novel
      statistical approach was applied to 1045 case-control samples from the Family
      Study of Cocaine Dependence. The results identify 330 low- to medium-effect size
      SNPs (i.e., those with a single-locus p-value of less than 10(-4)) that made a
      substantial contribution to cocaine dependence risk prediction (AUC = 0.718).
      Inclusion of six facets of environment and three personal characteristics yielded
      greater accuracy (AUC = 0.809). Of special importance was the joint effect of
      childhood abuse (CA) among trauma experiences and the GBE1 gene in cocaine
      dependence risk prediction. Genome-environmental risk-prediction models may
      become more promising in future risk-prediction research, once a more substantial
      array of environmental facets are taken into account, sometimes with model
      improvement when gene-by-environment product terms are included as part of these
      risk predication models.

PMID- 22629283
TI  - The genetic and epigenetic journey of embryonic stem cells into mature neural
      cells.
AB  - Epigenetic changes occur throughout life from embryonic development into
      adulthood. This results in the timely expression of developmentally important
      genes, determining the morphology and identity of different cell types and
      tissues within the body. Epigenetics regulate gene expression and cellular
      morphology through multiple mechanisms without alteration in the underlying DNA
      sequences. Different epigenetic mechanisms include chromatin condensation, post
      translational modification of histone proteins, DNA cytosine marks, and the
      activity of non-coding RNA molecules. Epigenetics play key roles in development,
      stem cell differentiation, and have high impact in human disease. In this review,
      we will discuss our current knowledge about these epigenetic mechanisms, with a
      focus on histone and DNA marks. We will then talk about the genetics and
      epigenetics of embryonic stem cell self-renewal and differentiation into neural
      stem cells, and further into specific neuronal cell types.

PMID- 22629286
TI  - Cardiovascular risk factors in portuguese obese children and adolescents: impact
      of small reductions in body mass index imposed by lifestyle modifications.
AB  - OBJECTIVES: Evaluate cardiovascular risk factors in Portuguese obese children and
      adolescents and the long-term effects of lifestyle modifications on such risk
      factors. DESIGN: Transversal cohort study and longitudinal study. SETTING:
      University Hospital S. Joao and Children's Hospital Maria Pia, Porto.
      PATIENTS/PARTICIPANTS: 148 obese children and adolescents [81 females (54.7%);
      mean age of 11.0 years] and 33 controls (sex and age matched) participated in a
      cross-sectional study. Sixty obese patients agreed to participate in an one year
      longitudinal study after medical and nutritionist appointments to improve
      lifestyle modification; a substantial body mass index (BMI) reduction was defined
      by a decrease in BMI z-score (BMI z-sc) of 0.3 or more over the studied period.
      MAIN OUTCOME MEASURES: Lipid profile (triglycerides, cholesterol, HDLc, LDLc,
      lipoprotein (a), apolipoproteins A and B) and circulating levels of C-reactive
      protein (CRP), adiponectin, glucose, and insulin. RESULTS: Compared with the lean
      children, obese patients demonstrated statistically significantly higher insulin
      resistance index [Homeostasis model assessment (HOMA)], and triglycerides, LDLc,
      apolipoprotein (apo) B, insulin and CRP concentrations, whereas their HDLc and
      apo A levels were significantly lower (cross-sectional study). In the
      longitudinal study (n=60), a substantial BMI reduction occurred in 17 (28.3%)
      obese patients which led to a significant reduction in triglycerides,
      cholesterol, LDLc, apo B, glucose and insulin levels and in HOMA. The DeltaBMI
      values over the studied period correlated inversely and significantly with BMI
      (P<0.001) and HOMA (P=0.026) values observed at baseline. In multiple linear
      regression analysis, BMI at baseline remained associated to changes in BMI over
      the studied period (standardised Beta: -0.271, P=0.05). CONCLUSION: Our data
      demonstrates that small reductions in BMI-zc, imposed by lifestyle modifications
      in obese children and adolescents, improve the cardiovascular risk profile of
      such patients. Furthermore, patients with higher BMI and/or insulin resistance
      seem to experience a greater relative reduction in their BMI after lifestyle
      improvements.

PMID- 22629287
TI  - Medical marijuana: clearing away the smoke.
AB  - Recent advances in understanding of the mode of action of tetrahydrocannabinol
      and related cannabinoid in-gredients of marijuana, plus the accumulating
      anecdotal reports on potential medical benefits have spurred increasing re-search
      into possible medicinal uses of cannabis. Recent clinical trials with smoked and
      vaporized marijuana, as well as other botanical extracts indicate the likelihood
      that the cannabinoids can be useful in the management of neuropathic pain,
      spasticity due to multiple sclerosis, and possibly other indications. As with all
      medications, benefits and risks need to be weighed in recommending cannabis to
      patients. We present an algorithm that may be useful to physicians in determining
      whether cannabis might be recommended as a treatment in jurisdictions where such
      use is permitted.

PMID- 22629288
TI  - Adverse events in patients with blood loss: a pooled analysis of 51 clinical
      studies from the celecoxib clinical trial database.
AB  - BACKGROUND: Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) is
      associated with an increased risk of gastrointestinal (GI) toxicity, including
      occult blood loss and the development of clinically significant anemia. The aim
      of this study was to investigate the clinical importance of clinically
      significant anemia/blood loss. METHODS: Pooled analysis of 51 blinded, controlled
      clinical studies >=4 weeks duration from the celecoxib clinical trial database,
      comparing celecoxib with NSAIDs or placebo. The adverse event (AE) profile in
      patients with clinically significant anemia/blood loss (defined as decreases in
      hemoglobin >=2 g/dL and/or hematocrit by >=10% from baseline) was compared with
      the AE profile in patients without blood loss. Events that occurred in <0.5% of
      patients were excluded from any comparisons. A threefold difference between
      groups was defined arbitrarily as being markedly higher. RESULTS: Overall
      932/51,048 patients experienced clinically significant anemia/blood loss.
      Baseline demographics were similar in both groups. The incidence of AEs was
      markedly higher in patients who experienced clinically significant anemia/blood
      loss than those who did not; the majority of these differences were for GI AEs or
      their likely sequelae. The incidence of the following non-GI related AEs was also
      markedly higher in patients with blood loss: coronary artery disease (1.2% vs
      0.3%), myocardial infarction (0.6% vs 0.2%), and pneumonia (1.7% vs 0.4%).
      Withdrawals due to AEs were more common among patients who experienced blood loss
      (16.7% vs 10.4%). CONCLUSIONS: Clinically significant anemia/blood loss may have
      clinically important adverse consequences beyond the sequelae previously known to
      be associated with NSAID-related GI effects.

PMID- 22629289
TI  - The Use of Preoperative Epoetin-alpha in Revision Hip Arthroplasty.
AB  - PURPOSE: To evaluate the efficacy of preoperative epoetin-alpha on the revision
      hip arthroplasty patient. We hypothesized that epoetin-alpha will reduce blood
      transfusion. A pertinent review of the literature is provided. METHODS: Forty-six
      patients were retrospectively reviewed. Sixteen patients received epoetin-alpha.
      Patients were case matched by age, preoperative hemoglobin, surgery, gender, and
      BMI. The clinical triggers for blood transfusion during or after the procedure
      were determined based on peri- and postoperative hemoglobin levels, ASA score,
      and/or clinical symptoms consistent with anemia. Blood salvage was not used.
      RESULTS: Blood transfusion and length of stay were decreased in the epoetin-alpha
      group. Hemoglobin in the intervention group increased from 12.0 to 14.5,
      preoperatively. Patients who received epoetin-alpha were 0.78 (RR=0.225) times as
      likely to receive a transfusion. Number Needed to Treat (NNT) to avoid one
      allogeneic transfusion was 1.84. Age, Gender, BMI, ASA, total and hidden blood
      loss, preoperative Iron supplements, preop Hct, preop PLT, PT, PTT, and INR were
      similar. One (6.0%) patient developed an uncomplicated deep venous thrombosis in
      the intervention group. CONCLUSIONS: The mildly anemic revision hip arthroplasty
      patient is at increased risk for transfusion. Epoetin-alpha increased
      preoperative hemoglobin counts and reduced transfusions in this study; it also
      decreased patient length of hospital stay likely allowing for an earlier
      readiness to resume normal activities and/or meet short-term milestones. A
      randomized study to evaluate the direct and indirect costs of such a treatment
      methodology in the mildly anemic revision patient may be warranted.

PMID- 22629290
TI  - Minimally invasive helical plating for shaft of humerus fractures: technique and
      outcome.
AB  - INTRODUCTION: The humerus is subjected to substantial amount of torsional stress.
      Conventional plating may not address this sufficiently and may lead to fixation
      failure or non-union. A helical plate may offer the solution. We present the
      surgical technique and functional outcome of 5 cases of humeral shaft fractures
      treated with this technique in a minimally invasive way. MATERIALS AND METHODS:
      The operations were performed between 2004 and 2010, by three surgeons. All the
      patients had closed humeral shaft fractures, either simple transverse or with
      mild comminution. Two small incisions were made. The proximal incision was placed
      along the deltopectoral groove over the shaft, and the distal incision was placed
      as in an antero-lateral approach. The radial nerve was identified and protected.
      A pre-selected plate was contoured and introduced in the submuscular plane. The
      plate was placed in a proximal-lateral and distal-anterior position. Screws were
      inserted through stab incisions. The patients were followed for an average of 6
      months. Functional recovery of the shoulder and elbow was assessed using the
      Constant and Mayo elbow performance score systems. RESULTS: All incisions healed
      by first intention without complications and all the fractures went on to unite.
      All patients achieved good to excellent shoulder and elbow function. CONCLUSION:
      The helical plate technique is a safe and effective method of treating humeral
      shaft fractures and has good functional outcome.

PMID- 22629291
TI  - Sciatica and incomplete paraplegia after spontaneous haematoma of the spinal cord
      due to a cumarine - induced coagulopathy: case report.
AB  - Spontaneous spinal haematoma is a rare cause of sciatica. We present a case of a
      73 year old patient, who was admitted to our department and suffered from
      spontaneous sciatica over 24 hours. During the examination, the patient presented
      undulating symptoms of paraplegia, varying from incomplete loss of power in the
      left lower limb to complete plegia. The patient presented multiple diseases like
      biological aortic valve replacement, diabetes, hypertonia in her medical history,
      etc. Due to an additional absolute arrhythmia she ingested a cumarine medication.
      The tomographic imaging revealed a spontaneous lumbar and cranial subarachnoidal
      haematoma.

PMID- 22629292
TI  - BMP-2 Dependent Increase of Soft Tissue Density in Arthrofibrotic TKA.
AB  - Arthrofibrosis after total knee arthroplasty (TKA) is difficult to treat, as its
      aetiology remains unclear. In a previous study, we established a connection
      between the BMP-2 concentration in the synovial fluid and arthrofibrosis after
      TKA. The hypothesis of the present study was, therefore, that the limited range
      of motion in arthrofibrosis is caused by BMP-2 induced heterotopic ossifications,
      the quantity of which is dependent on the BMP-2 concentration in the synovial
      fluid.Eight patients with arthrofibrosis after TKA were included. The
      concentration of BMP-2 in the synovial fluid from each patient was determined by
      ELISA. Radiologically, digital radiographs were evaluated and the grey scale
      values were determined as a measure of the tissue density of defined areas. Apart
      from air, cutis, subcutis and muscle, the soft-tissue density in the area of the
      capsule of the suprapatellar pouch was determined. The connection between the BMP
      2 concentration and the soft-tissue density was then investigated.The average BMP
      2 concentration in the synovial fluid was 24.3 +/- 6.9 pg/ml. The density of the
      anterior knee capsule was on average 136 +/- 35 grey scale values. A linear
      correlation was shown between the BMP-2 concentration in the synovial fluid and
      the radiological density of the anterior joint capsule (R=0.84, p = 0.009).We
      were able to show that there is a connection between BMP-2 concentration and soft
      tissue density in arthrofibrosis after TKA. This opens up the possibility of
      conducting a prophylaxis against arthrofibrosis in risk patients by influencing
      the BMP-2 pathway.

PMID- 22629293
TI  - Reviewing the medical literature: five notable articles in general internal
      medicine from 2010 and 2011.

PMID- 22629294
TI  - Optimization for the production of surfactin with a new synergistic antifungal
      activity.
AB  - BACKGROUND: Two of our long term efforts are to discover compounds with
      synergistic antifungal activity from metabolites of marine derived microbes and
      to optimize the production of the interesting compounds produced by
      microorganisms. In this respect, new applications or mechanisms of already known
      compounds with a high production yield could be continually identified. Surfactin
      is a well-known lipopeptide biosurfactant with a broad spectrum of antimicrobial
      and antiviral activity; however, there is less knowledge on surfactin's
      antifungal activity. In this study, we investigated the synergistic antifungal
      activity of C(15)-surfactin and the optimization of its production by the
      response surface method. METHODOLOGY/PRINCIPAL FINDINGS: Using a synergistic
      antifungal screening model, we found that the combination of C(15)-surfactin and
      ketoconazole (KTC) showed synergistic antifungal effect on Candida albicans
      SC5314 when the concentrations of C(15)-surfactin and KTC were 6.25 ug/mL and
      0.004 ug/mL, respectively. These concentrations were lower than their own
      efficient antifungal concentrations, which are >100 ug/mL and 0.016 ug/mL,
      respectively. The production of C(15)-surfactin from Bacillus amyloliquefaciens
      was optimized by the response surface methodology in shaker flask cultivation.
      The Plackett-Burman design found sucrose, ammonium nitrate and NaH(2)PO(4) x
      2H(2)O to have significant effects on C(15)-surfactin production. The optimum
      values of the tested variables were 21.17 g/L sucrose, 2.50 g/L ammonium nitrate
      and 11.56 g/L NaH(2)PO(4).2H(2)O. A production of 134.2 mg/L, which were in
      agreement with the prediction, was observed in a verification experiment. In
      comparison to the production of original level (88.6 mg/L), a 1.52-fold increase
      had been obtained. CONCLUSION/SIGNIFICANCE: This work first found that C(15)
      surfactin was an efficient synergistic antifungal agent, and demonstrated that
      response surface methodology was an effective method to improve the production of
      C(15)-surfactin.

PMID- 22629295
TI  - Globular adiponectin activates motility and regenerative traits of muscle
      satellite cells.
AB  - Regeneration of adult injured skeletal muscle is due to activation of satellite
      cells, a population of stem cells resident beneath the basal lamina. Thus,
      information on soluble factors affecting satellite cell activation, as well as
      migration towards injury and fusion into new myofibers are essential. Here, we
      show that globular adiponectin (gAd), positively affects several features of
      muscle satellite cells. gAd activates satellite cells to exit quiescence and
      increases their recruitment towards myotubes. gAd elicits in satellite cells a
      specific motility program, involving activation of the small GTPase Rac1, as well
      as expression of Snail and Twist transcription factors driving a proteolytic
      motility, useful to reach the site of injury. We show that satellite cells
      produce autocrine full length adiponectin (fAd), which is converted to gAd by
      activated macrophages. In turns, gAd concurs to attract to the site of injury
      both satellite cells and macrophages and induces myogenesis in muscle satellite
      cells. Thus, these findings add a further role for gAd in skeletal muscle,
      including the hormone among factors participating in muscle regeneration.

PMID- 22629296
TI  - A pilot trial assessing urinary gene expression profiling with an mRNA array for
      diabetic nephropathy.
AB  - BACKGROUND: The initiation and progression of diabetic nephropathy (DN) is
      complex. Quantification of mRNA expression in urinary sediment has emerged as a
      novel strategy for studying renal diseases. Considering the numerous molecules
      involved in DN development, a high-throughput platform with parallel detection of
      multiple mRNAs is needed. In this study, we constructed a self-assembling mRNA
      array to analyze urinary mRNAs in DN patients with aims to reveal its potential
      in searching novel biomarkers. METHODS: mRNA array containing 88 genes were
      fabricated and its performance was evaluated. A pilot study with 9 subjects
      including 6 DN patients and 3 normal controls were studied with the array. DN
      patients were assigned into two groups according to their estimate glomerular
      rate (eGFR): DNI group (eGFR>60 ml/min/1.73 m(2), n = 3) and DNII group (eGFR<60
      ml/min/1.73 m(2), n = 3). Urinary cell pellet was collected from each study
      participant. Relative abundance of these target mRNAs from urinary pellet was
      quantified with the array. RESULTS: The array we fabricated displayed high
      sensitivity and specificity. Moreover, the Cts of Positive PCR Controls in our
      experiments were 24+/-0.5 which indicated high repeatability of the array. A
      total of 29 mRNAs were significantly increased in DN patients compared with
      controls (p<0.05). Among these genes, alpha-actinin4, CDH2, ACE, FAT1,
      synaptopodin, COL4alpha, twist, NOTCH3 mRNA expression were 15-fold higher than
      those in normal controls. In contrast, urinary TIMP-1 mRNA was significantly
      decreased in DN patients (p<0.05). It was shown that CTGF, MCP-1, PAI-1, ACE,
      CDH1, CDH2 mRNA varied significantly among the 3 study groups, and their mRNA
      levels increased with DN progression (p<0.05). CONCLUSION: Our pilot study
      demonstrated that mRNA array might serve as a high-throughput and sensitive tool
      for detecting mRNA expression in urinary sediment. Thus, this primary study
      indicated that mRNA array probably could be a useful tool for searching new
      biomarkers for DN.

PMID- 22629297
TI  - ROS-mediated decline in maximum Ca2+-activated force in rat skeletal muscle
      fibers following in vitro and in vivo stimulation.
AB  - We hypothesised that normal skeletal muscle stimulated intensely either in vitro
      or in situ would exhibit reactive oxygen species (ROS)-mediated contractile
      apparatus changes common to many pathophysiological conditions. Isolated soleus
      (SOL) and extensor digitorum longus (EDL) muscles of the rat were bubbled with
      95% O(2) and stimulated in vitro at 31 degrees C to give isometric tetani (50 Hz
      for 0.5 s every 2 s) until maximum force declined to <=30%. Skinned superficial
      slow-twitch fibers from the SOL muscles displayed a large reduction (~41%) in
      maximum Ca(2+)-activated specific force (F(max)), with Ca(2+)-sensitivity
      unchanged. Fibers from EDL muscles were less affected. The decrease in F(max) in
      SOL fibers was evidently due to oxidation effects on cysteine residues because it
      was reversed if the reducing agent DTT was applied prior to activating the fiber.
      The GSH:GSSG ratio was ~3-fold lower in the cytoplasm of superficial fibers from
      stimulated muscle compared to control, confirming increased oxidant levels. The
      presence of Tempol and L-NAME during in vitro stimulation prevented reduction in
      F(max). Skinned fibers from SOL muscles stimulated in vivo at 37 degrees C with
      intact blood supply also displayed reduction in F(max), though to a much smaller
      extent (~12%). Thus, fibers from muscles stimulated even with putatively adequate
      O(2) supply display a reversible oxidation-induced decrease in F(max) without
      change in Ca(2+)-sensitivity, consistent with action of peroxynitrite (or
      possibly superoxide) on cysteine residues of the contractile apparatus.
      Significantly, the changes closely resemble the contractile deficits observed in
      a range of pathophysiological conditions. These findings highlight how readily
      muscle experiences ROS-related deficits, and also point to potential difficulties
      when defining muscle performance and fatigue.

PMID- 22629298
TI  - High-throughput sequence analysis of turbot (Scophthalmus maximus) transcriptome
      using 454-pyrosequencing for the discovery of antiviral immune genes.
AB  - BACKGROUND: Turbot (Scophthalmus maximus L.) is an important aquacultural
      resource both in Europe and Asia. However, there is little information on gene
      sequences available in public databases. Currently, one of the main problems
      affecting the culture of this flatfish is mortality due to several pathogens,
      especially viral diseases which are not treatable. In order to identify new genes
      involved in immune defense, we conducted 454-pyrosequencing of the turbot
      transcriptome after different immune stimulations. METHODOLOGY/PRINCIPAL
      FINDINGS: Turbot were injected with viral stimuli to increase the expression
      level of immune-related genes. High-throughput deep sequencing using 454
      pyrosequencing technology yielded 915,256 high-quality reads. These sequences
      were assembled into 55,404 contigs that were subjected to annotation steps.
      Intriguingly, 55.16% of the deduced protein was not significantly similar to any
      sequences in the databases used for the annotation and only 0.85% of the BLASTx
      top-hits matched S. maximus protein sequences. This relatively low level of
      annotation is possibly due to the limited information for this specie and other
      flatfish in the database. These results suggest the identification of a large
      number of new genes in turbot and in fish in general. A more detailed analysis
      showed the presence of putative members of several innate and specific immune
      pathways. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this study is the first
      transcriptome analysis using 454-pyrosequencing for turbot. Previously, there
      were only 12,471 EST and less of 1,500 nucleotide sequences for S. maximus in
      NCBI database. Our results provide a rich source of data (55,404 contigs and
      181,845 singletons) for discovering and identifying new genes, which will serve
      as a basis for microarray construction, gene expression characterization and for
      identification of genetic markers to be used in several applications. Immune
      stimulation in turbot was very effective, obtaining an enormous variety of
      sequences belonging to genes involved in the defense mechanisms.

PMID- 22629299
TI  - Optical silencing of C. elegans cells with arch proton pump.
AB  - BACKGROUND: Optogenetic techniques using light-driven ion channels or ion pumps
      for controlling excitable cells have greatly facilitated the investigation of
      nervous systems in vivo. A model organism, C. elegans, with its small transparent
      body and well-characterized neural circuits, is especially suitable for
      optogenetic analyses. METHODOLOGY/PRINCIPAL FINDINGS: We describe the application
      of archaerhodopsin-3 (Arch), a recently reported optical neuronal silencer, to C.
      elegans. Arch::GFP expressed either in all neurons or body wall muscles of the
      entire body by means of transgenes were localized, at least partially, to the
      cell membrane without adverse effects, and caused locomotory paralysis of worms
      when illuminated by green light (550 nm). Pan-neuronal expression of Arch endowed
      worms with quick and sustained responsiveness to such light. Worms reliably
      responded to repeated periods of illumination and non-illumination, and remained
      paralyzed under continuous illumination for 30 seconds. Worms expressing Arch in
      different subsets of motor neurons exhibited distinct defects in the locomotory
      behavior under green light: selective silencing of A-type motor neurons affected
      backward movement while silencing of B-type motor neurons affected forward
      movement more severely. Our experiments using a heat-shock-mediated induction
      system also indicate that Arch becomes fully functional only 12 hours after
      induction and remains functional for more than 24 hour.  CONCLUSIONS/SGNIFICANCE:
      Arch can be used for silencing neurons and muscles, and may be a useful
      alternative to currently widely used halorhodopsin (NpHR) in optogenetic studies
      of C. elegans.

PMID- 22629300
TI  - A new cationic porphyrin derivative (TMPipEOPP) with large side arm substituents:
      a highly selective G-quadruplex optical probe.
AB  - The discovery of uncommon DNA structures and speculation about their potential
      functions in genes has brought attention to specific DNA structure recognition. G
      quadruplexes are four-stranded nucleic acid structures formed by G-rich DNA (or
      RNA) sequences. G-rich sequences with a high potential to form G-quadruplexes
      have been found in many important genomic regions. Porphyrin derivatives with
      cationic side arm substituents are important G-quadruplex-binding ligands. For
      example, 5,10,15,20-Tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphyrin (TMPyP4),
      interacts strongly with G-quadruplexes, but has poor selectivity for G-quadruplex
      versus duplex DNA. To increase the G-quadruplex recognition specificity, a new
      cationic porphyrin derivative, 5,10,15,20-tetra-{4-[2-(1-methyl-1
      piperidinyl)ethoxy]phenyl} porphyrin (TMPipEOPP), with large side arm
      substituents was synthesized, and the interactions between TMPipEOPP and
      different DNA structures were compared. The results show that G-quadruplexes
      cause large changes in the UV-Vis absorption and fluorescence spectra of
      TMPipEOPP, but duplex and single-stranded DNAs do not, indicating that TMPipEOPP
      can be developed as a highly specific optical probe for discriminating G
      quadruplex from duplex and single-stranded DNA. Visual discrimination is also
      possible. Job plot and Scatchard analysis suggest that a complicated binding
      interaction occurs between TMPipEOPP and G-quadruplexes. At a low [G
      quadruplex]/[TMPipEOPP] ratio, one G-quadruplex binds two TMPipEOPP molecules by
      end-stacking and outside binding modes. At a high [G-quadruplex]/[TMPipEOPP]
      ratio, two G-quadruplexes bind to one TMPipEOPP molecule in a sandwich-like end
      stacking mode.

PMID- 22629301
TI  - Interspecific germline transmission of cultured primordial germ cells.
AB  - In birds, the primordial germ cell (PGC) lineage separates from the soma within
      24 h following fertilization. Here we show that the endogenous population of
      about 200 PGCs from a single chicken embryo can be expanded one million fold in
      culture. When cultured PGCs are injected into a xenogeneic embryo at an
      equivalent stage of development, they colonize the testis. At sexual maturity,
      these donor PGCs undergo spermatogenesis in the xenogeneic host and become
      functional sperm. Insemination of semen from the xenogeneic host into females
      from the donor species produces normal offspring from the donor species. In our
      model system, the donor species is chicken (Gallus domesticus) and the recipient
      species is guinea fowl (Numida meleagris), a member of a different avian family,
      suggesting that the mechanisms controlling proliferation of the germline are
      highly conserved within birds. From a pragmatic perspective, these data are the
      basis of a novel strategy to produce endangered species of birds using
      domesticated hosts that are both tractable and fecund.

PMID- 22629303
TI  - Revealing the appetite of the marine aquarium fish trade: the volume and
      biodiversity of fish imported into the United States.
AB  - The aquarium trade and other wildlife consumers are at a crossroads forced by
      threats from global climate change and other anthropogenic stressors that have
      weakened coastal ecosystems. While the wildlife trade may put additional stress
      on coral reefs, it brings income into impoverished parts of the world and may
      stimulate interest in marine conservation. To better understand the influence of
      the trade, we must first be able to quantify coral reef fauna moving through it.
      Herein, we discuss the lack of a data system for monitoring the wildlife aquarium
      trade and analyze problems that arise when trying to monitor the trade using a
      system not specifically designed for this purpose. To do this, we examined an
      entire year of import records of marine tropical fish entering the United States
      in detail, and discuss the relationship between trade volume, biodiversity and
      introduction of non-native marine fishes. Our analyses showed that biodiversity
      levels are higher than previous estimates. Additionally, more than half of
      government importation forms have numerical or other reporting discrepancies
      resulting in the overestimation of trade volumes by 27%. While some commonly
      imported species have been introduced into the coastal waters of the USA (as
      expected), we also found that some uncommon species in the trade have also been
      introduced. This is the first study of aquarium trade imports to compare
      commercial invoices to government forms and provides a means to, routinely and in
      real time, examine the biodiversity of the trade in coral reef wildlife species.

PMID- 22629302
TI  - Naturally occurring culturable aerobic gut flora of adult Phlebotomus papatasi,
      vector of Leishmania major in the Old World.
AB  - BACKGROUND: Cutaneous leishmaniasis is a neglected, vector-borne parasitic
      disease and is responsible for persistent, often disfiguring lesions and other
      associated complications. Leishmania, causing zoonotic cutaneous leishmaniasis
      (ZCL) in the Old World are mainly transmitted by the predominant sand fly vector,
      Phlebotomus papatasi. To date, there is no efficient control measure or vaccine
      available for this widespread insect-borne infectious disease.
      METHODOLOGY/PRINCIPAL FINDINGS: A survey was carried out to study the abundance
      of different natural gut flora in P. papatasi, with the long-term goal of
      generating a paratransgenic sand fly that can potentially block the development
      of Leishmania in the sand fly gut, thereby preventing transmission of leishmania
      in endemic disease foci. Sand flies, in particular, P. papatasi were captured
      from different habitats of various parts of the world. Gut microbes were cultured
      and identified using 16S ribosomal DNA analysis and a phylogenetic tree was
      constructed. We found variation in the species and abundance of gut flora in
      flies collected from different habitats. However, a few Gram-positive,
      nonpathogenic bacteria including Bacillus flexus and B. pumilus were common in
      most of the sites examined. CONCLUSION/SIGNIFICANCE: Our results indicate that
      there is a wide range of variation of aerobic gut flora inhabiting sand fly guts,
      which possibly reflect the ecological condition of the habitat where the fly
      breeds. Also, some species of bacteria (B. pumilus, and B. flexus) were found
      from most of the habitats. Important from an applied perspective of
      dissemination, our results support a link between oviposition induction and adult
      gut flora.

PMID- 22629304
TI  - The RIP140 gene is a transcriptional target of E2F1.
AB  - RIP140 is a transcriptional coregulator involved in energy homeostasis and
      ovulation which is controlled at the transcriptional level by several nuclear
      receptors. We demonstrate here that RIP140 is a novel target gene of the E2F1
      transcription factor. Bioinformatics analysis, gel shift assay, and chromatin
      immunoprecipitation demonstrate that the RIP140 promoter contains bona fide E2F
      response elements. In transiently transfected MCF-7 breast cancer cells, the
      RIP140 promoter is transactivated by overexpression of E2F1/DP1. Interestingly,
      RIP140 mRNA is finely regulated during cell cycle progression (5-fold increase at
      the G1/S and G2/M transitions). The positive regulation by E2F1 requires
      sequences located in the proximal region of the promoter (-73/+167), involves Sp1
      transcription factors, and undergoes a negative feedback control by RIP140.
      Finally, we show that E2F1 participates in the induction of RIP140 expression
      during adipocyte differentiation. Altogether, this work identifies the RIP140
      gene as a new transcriptional target of E2F1 which may explain some of the effect
      of E2F1 in both cancer and metabolic diseases.

PMID- 22629305
TI  - Effects of acute tryptophan depletion on brain serotonin function and
      concentrations of dopamine and norepinephrine in C57BL/6J and BALB/cJ mice.
AB  - Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT).
      Administration of large neutral amino acids (LNAA) limits the transport of
      endogenous tryptophan (TRP) across the blood brain barrier by competition with
      other LNAAs and subsequently decreases serotonergic neurotransmission. A recent
      discussion on the specificity and efficacy of the ATD paradigm for inhibition of
      central nervous 5-HT has arisen. Moreover, side effects such as vomiting and
      nausea after intake of amino acids (AA) still limit its use. ATD Moja-De is a
      revised mixture of AAs which is less nauseating than conventional protocols. It
      has been used in preliminary clinical studies but its effects on central 5-HT
      mechanisms and other neurotransmitter systems have not been validated in an
      animal model. We tested ATD Moja-De (TRP-) in two strains of mice: C57BL/6J, and
      BALB/cJ, which are reported to have impaired 5-HT synthesis and a more anxious
      phenotype relative to other strains of mice. ATD Moja-De lowered brain TRP,
      significantly decreased 5-HT synthesis as indexed by 5-HTP levels after
      decarboxlyase inhibition, and lowered 5-HT and 5-HIAA in both strains of mice,
      however more so in C57BL/6J than in BALB/cJ. Dopamine and its metabolites as well
      as norepinephrine were not affected. A balanced (TRP+) control mixture did not
      raise 5-HT or 5-HIAA. The present findings suggest that ATD Moja-De effectively
      and specifically suppresses central serotonergic function. These results also
      demonstrate a strain-specific effect of ATD Moja-De on anxiety-like behavior.

PMID- 22629306
TI  - Investigation of the biosynthetic potential of endophytes in traditional Chinese
      anticancer herbs.
AB  - Traditional Chinese medicine encompasses a rich empirical knowledge of the use of
      plants for the treatment of disease. In addition, the microorganisms associated
      with medicinal plants are also of interest as the producers of the compounds
      responsible for the observed plant bioactivity. The present study has pioneered
      the use of genetic screening to assess the potential of endophytes to synthesize
      bioactive compounds, as indicated by the presence of non-ribosomal peptide
      synthetase (NRPS) and polyketide synthase (PKS) genes. The total DNA extracts of
      30 traditional Chinese herbs, were screened for functional genes involved in the
      biosynthesis of bioactive compounds. The four PCR screens were successful in
      targeting four bacterial PKS, six bacterial NRPS, ten fungal PKS and three fungal
      NRPS gene fragments. Analysis of the detected endophyte gene fragments afforded
      consideration of the possible bioactivity of the natural products produced by
      endophytes in medicinal herbs. This investigation describes a rapid method for
      the initial screening of medicinal herbs and has highlighted a subset of those
      plants that host endophytes with biosynthetic potential. These selected plants
      can be the focus of more comprehensive endophyte isolation and natural product
      studies.

PMID- 22629307
TI  - Divergent modulation of neuronal differentiation by caspase-2 and -9.
AB  - Human Ntera2/cl.D1 (NT2) cells treated with retinoic acid (RA) differentiate
      towards a well characterized neuronal phenotype sharing many features with human
      fetal neurons. In view of the emerging role of caspases in murine stem
      cell/neural precursor differentiation, caspases activity was evaluated during RA
      differentiation. Caspase-2, -3 and -9 activity was transiently and selectively
      increased in differentiating and non-apoptotic NT2-cells. SiRNA-mediated
      selective silencing of either caspase-2 (si-Casp2) or -9 (si-Casp9) was
      implemented in order to dissect the role of distinct caspases. The RA-induced
      expression of neuronal markers, i.e. neural cell adhesion molecule (NCAM),
      microtubule associated protein-2 (MAP2) and tyrosine hydroxylase (TH) mRNAs and
      proteins, was decreased in si-Casp9, but markedly increased in si-Casp2 cells.
      During RA-induced NT2 differentiation, the class III histone deacetylase Sirt1, a
      putative caspase substrate implicated in the regulation of the proneural bHLH
      MASH1 gene expression, was cleaved to a ~100 kDa fragment. Sirt1 cleavage was
      markedly reduced in si-Casp9 cells, even though caspase-3 was normally activated,
      but was not affected (still cleaved) in si-Casp2 cells, despite a marked
      reduction of caspase-3 activity. The expression of MASH1 mRNA was higher and
      occurred earlier in si-Casp2 cells, while was reduced at early time points during
      differentiation in si-Casp9 cells. Thus, caspase-2 and -9 may perform opposite
      functions during RA-induced NT2 neuronal differentiation. While caspase-9
      activation is relevant for proper neuronal differentiation, likely through the
      fine tuning of Sirt1 function, caspase-2 activation appears to hinder the RA
      induced neuronal differentiation of NT2 cells.

PMID- 22629308
TI  - Parallel alterations of functional connectivity during execution and imagination
      after motor imagery learning.
AB  - BACKGROUND: Neural substrates underlying motor learning have been widely
      investigated with neuroimaging technologies. Investigations have illustrated the
      critical regions of motor learning and further revealed parallel alterations of
      functional activation during imagination and execution after learning. However,
      little is known about the functional connectivity associated with motor learning,
      especially motor imagery learning, although benefits from functional connectivity
      analysis attract more attention to the related explorations. We explored whether
      motor imagery (MI) and motor execution (ME) shared parallel alterations of
      functional connectivity after MI learning. METHODOLOGY/PRINCIPAL FINDINGS: Graph
      theory analysis, which is widely used in functional connectivity exploration, was
      performed on the functional magnetic resonance imaging (fMRI) data of MI and ME
      tasks before and after 14 days of consecutive MI learning. The control group had
      no learning. Two measures, connectivity degree and interregional connectivity,
      were calculated and further assessed at a statistical level. Two interesting
      results were obtained: (1) The connectivity degree of the right posterior
      parietal lobe decreased in both MI and ME tasks after MI learning in the
      experimental group; (2) The parallel alterations of interregional connectivity
      related to the right posterior parietal lobe occurred in the supplementary motor
      area for both tasks. CONCLUSIONS/SIGNIFICANCE: These computational results may
      provide the following insights: (1) The establishment of motor schema through MI
      learning may induce the significant decrease of connectivity degree in the
      posterior parietal lobe; (2) The decreased interregional connectivity between the
      supplementary motor area and the right posterior parietal lobe in post-test
      implicates the dissociation between motor learning and task performing. These
      findings and explanations further revealed the neural substrates underpinning MI
      learning and supported that the potential value of MI learning in motor function
      rehabilitation and motor skill learning deserves more attention and further
      investigation.

PMID- 22629309
TI  - Near-real-time acoustic monitoring of beaked whales and other cetaceans using a
      SeagliderTM.
AB  - In most areas, estimating the presence and distribution of cryptic marine mammal
      species, such as beaked whales, is extremely difficult using traditional
      observational techniques such as ship-based visual line transect surveys. Because
      acoustic methods permit detection of animals underwater, at night, and in poor
      weather conditions, passive acoustic observation has been used increasingly often
      over the last decade to study marine mammal distribution, abundance, and
      movements, as well as for mitigation of potentially harmful anthropogenic
      effects. However, there is demand for new, cost-effective tools that allow
      scientists to monitor areas of interest autonomously with high temporal and
      spatial resolution in near-real time. Here we describe an autonomous underwater
      vehicle--a glider--equipped with an acoustic sensor and onboard data processing
      capabilities to passively scan an area for marine mammals in near-real time. The
      glider was tested extensively off the west coast of the Island of Hawai'i, USA.
      The instrument covered approximately 390 km during three weeks at sea and
      collected a total of 194 h of acoustic data. Detections of beaked whales were
      successfully reported to shore in near-real time. Manual analysis of the recorded
      data revealed a high number of vocalizations of delphinids and sperm whales.
      Furthermore, the glider collected vocalizations of unknown origin very similar to
      those made by known species of beaked whales. The instrument developed here can
      be used to cost-effectively screen areas of interest for marine mammals for
      several months at a time. The near-real-time detection and reporting capabilities
      of the glider can help to protect marine mammals during potentially harmful
      anthropogenic activities such as seismic exploration for sub-sea fossil fuels or
      naval sonar exercises. Furthermore, the glider is capable of under-ice operation,
      allowing investigation of otherwise inaccessible polar environments that are
      critical habitats for many endangered marine mammal species.

PMID- 22629310
TI  - Inhibition of 26S protease regulatory subunit 7 (MSS1) suppresses
      neuroinflammation.
AB  - Recently, researchers have focused on immunosuppression induced by rifampicin.
      Our previous investigation found that rifampicin was neuroprotective by
      inhibiting the production of pro-inflammatory mediators, thereby suppressing
      microglial activation. In this study, using 2-dimensional gel electrophoresis (2
      DE) and mass spectrometry (MS), we discovered that 26S protease regulatory
      subunit 7 (MSS1) was decreased in rifampicin-treated microglia. Western blot
      analysis verified the downregulation of MSS1 expression by rifampicin. As it is
      indicated that the modulation of the ubiquitin-26S proteasome system (UPS) with
      proteasome inhibitors is efficacious for the treatment of neuro-inflammatory
      disorders, we next hypothesized that silencing MSS1 gene expression might inhibit
      microglial inflammation. Using RNA interference (RNAi), we showed significant
      reduction of IkBalpha degradation and NF-kB activation. The production of
      lipopolysaccharides-induced pro-inflammatory mediators such as inducible nitric
      oxide synthase (iNOS), nitric oxide, cyclooxygenase-2, and prostaglandin E(2)
      were also reduced by MSS1 gene knockdown. Taken together, our findings suggested
      that rifampicin inhibited microglial inflammation by suppressing MSS1 protein
      production. Silencing MSS1 gene expression decreased neuroinflammation. We
      concluded that MSS1 inhibition, in addition to anti-inflammatory rifampicin,
      might represent a novel mechanism for the treatment of neuroinflammatory
      disorders.

PMID- 22629311
TI  - Measurement of ad libitum food intake, physical activity, and sedentary time in
      response to overfeeding.
AB  - Given the wide availability of highly palatable foods, overeating is common.
      Energy intake and metabolic responses to overfeeding may provide insights into
      weight gain prevention. We hypothesized a down-regulation in subsequent food
      intake and sedentary time, and up-regulation in non-exercise activity and core
      temperature in response to overfeeding in order to maintain body weight constant.
      In a monitored inpatient clinical research unit using a cross over study design,
      we investigated ad libitum energy intake (EI, using automated vending machines),
      core body temperature, and physical activity (using accelerometry) following a
      short term (3-day) weight maintaining (WM) vs overfeeding (OF) diet in healthy
      volunteers (n = 21, BMI, mean +/- SD, 33.2+/-8.6 kg/m(2), 73.6% male). During the
      ad libitum periods following the WM vs. OF diets, there was no significant
      difference in mean 3-d EI (4061+/-1084 vs. 3926+/-1284 kcal/day, p = 0.41), and
      there were also no differences either in core body temperature (37.0+/-0.2
      degrees C vs. 37.1+/-0.2 degrees C, p = 0.75) or sedentary time (70.9+/-12.9 vs.
      72.0+/-7.4%, p = 0.88). However, during OF (but not WM), sedentary time was
      positively associated with weight gain (r = 0.49, p = 0.05, adjusted for age,
      sex, and initial weight). In conclusion, short term overfeeding did not result in
      a decrease in subsequent ad libitum food intake or overall change in sedentary
      time although in secondary analysis sedentary time was associated with weight
      gain during OF. Beyond possible changes in sedentary time, there is minimal
      attempt to restore energy balance during or following short term overfeeding.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00342732.

PMID- 22629312
TI  - The (mis)reporting of male circumcision status among men and women in Zambia and
      Swaziland: a randomized evaluation of interview methods.
AB  - BACKGROUND: To date, male circumcision prevalence has been estimated using
      surveys of men self-reporting their circumcision status. HIV prevention trials
      and observational studies involving female participants also collect data on
      partners' circumcision status as a risk factor for HIV/STIs. A number of studies
      indicate that reports of circumcision status may be inaccurate. This study
      assessed different methods for improving self- and partner reporting of
      circumcision status. METHODS/FINDINGS: The study was conducted in urban and rural
      Zambia and urban Swaziland. Men (N = 1264) aged 18-50 and their female partners
      (N = 1264), and boys (N = 840) aged 13-17 were enrolled. Participants were
      recruited from HIV counseling and testing sites, health centers, and surrounding
      communities. The study experimentally assessed methods for improving the
      reporting of circumcision status, including: a) a simple description of
      circumcision, b) a detailed description of circumcision, c) an illustration of a
      circumcised and uncircumcised penis, and d) computerized self-interviewing. Self
      reports were compared to visual examination. For men, the error in reporting was
      largely unidirectional: uncircumcised men more often reported they were
      circumcised (2-7%), depending on setting. Fewer circumcised men misrepresented
      their status (0.05-5%). Misreporting by women was significantly higher (11-15%),
      with the error in both directions. A sizable number of women reported that they
      did not know their partner's circumcision status (3-8%). Computerized
      interviewing did not improve accuracy. Providing an illustration, particularly
      for illiterate participants, significantly improved reporting of circumcision
      status, decreasing misreporting among illiterate participants from 13% to 10%,
      although misreporting was not eliminated. CONCLUSIONS: Study results suggest that
      the prevalence of circumcision may be overestimated in Zambia and Swaziland; the
      error in reporting is higher among women than among men. Improved reporting when
      a description or illustration is provided suggests that the source of the error
      is a lack of understanding of male circumcision.

PMID- 22629313
TI  - Chemical inhibition of bacterial protein tyrosine phosphatase suppresses capsule
      production.
AB  - Capsule polysaccharide is a major virulence factor for a wide range of bacterial
      pathogens, including Streptococcus pneumoniae. The biosynthesis of Wzy-dependent
      capsules in both gram-negative and -positive bacteria is regulated by a system
      involving a protein tyrosine phosphatase (PTP) and a protein tyrosine kinase.
      However, how the system functions is still controversial. In Streptococcus
      pneumoniae, a major human pathogen, the system is present in all but 2 of the 93
      serotypes found to date. In order to study this regulation further, we performed
      a screen to find inhibitors of the phosphatase, CpsB. This led to the observation
      that a recently discovered marine sponge metabolite, fascioquinol E, inhibited
      CpsB phosphatase activity both in vitro and in vivo at concentrations that did
      not affect the growth of the bacteria. This inhibition resulted in decreased
      capsule synthesis in D39 and Type 1 S. pneumoniae. Furthermore, concentrations of
      Fascioquinol E that inhibited capsule also lead to increased attachment of
      pneumococci to a macrophage cell line, suggesting that this compound would
      inhibit the virulence of the pathogen. Interestingly, this compound also
      inhibited the phosphatase activity of the structurally unrelated gram-negative
      PTP, Wzb, which belongs to separate family of protein tyrosine phosphatases.
      Furthermore, incubation with Klebsiella pneumoniae, which contains a homologous
      phosphatase, resulted in decreased capsule synthesis. Taken together, these data
      provide evidence that PTPs are critical for Wzy-dependent capsule production
      across a spectrum of bacteria, and as such represents a valuable new molecular
      target for the development of anti-virulence antibacterials.

PMID- 22629314
TI  - A multi-label predictor for identifying the subcellular locations of singleplex
      and multiplex eukaryotic proteins.
AB  - Subcellular locations of proteins are important functional attributes. An
      effective and efficient subcellular localization predictor is necessary for
      rapidly and reliably annotating subcellular locations of proteins. Most of
      existing subcellular localization methods are only used to deal with single
      location proteins. Actually, proteins may simultaneously exist at, or move
      between, two or more different subcellular locations. To better reflect
      characteristics of multiplex proteins, it is highly desired to develop new
      methods for dealing with them. In this paper, a new predictor, called Euk-ECC
      mPLoc, by introducing a powerful multi-label learning approach which exploits
      correlations between subcellular locations and hybridizing gene ontology with
      dipeptide composition information, has been developed that can be used to deal
      with systems containing both singleplex and multiplex eukaryotic proteins. It can
      be utilized to identify eukaryotic proteins among the following 22 locations: (1)
      acrosome, (2) cell membrane, (3) cell wall, (4) centrosome, (5) chloroplast, (6)
      cyanelle, (7) cytoplasm, (8) cytoskeleton, (9) endoplasmic reticulum, (10)
      endosome, (11) extracellular, (12) Golgi apparatus, (13) hydrogenosome, (14)
      lysosome, (15) melanosome, (16) microsome, (17) mitochondrion, (18) nucleus, (19)
      peroxisome, (20) spindle pole body, (21) synapse, and (22) vacuole. Experimental
      results on a stringent benchmark dataset of eukaryotic proteins by jackknife
      cross validation test show that the average success rate and overall success rate
      obtained by Euk-ECC-mPLoc were 69.70% and 81.54%, respectively, indicating that
      our approach is quite promising. Particularly, the success rates achieved by Euk
      ECC-mPLoc for small subsets were remarkably improved, indicating that it holds a
      high potential for simulating the development of the area. As a user-friendly web
      server, Euk-ECC-mPLoc is freely accessible to the public at the website
      http://levis.tongji.edu.cn:8080/bioinfo/Euk-ECC-mPLoc/. We believe that Euk-ECC
      mPLoc may become a useful high-throughput tool, or at least play a complementary
      role to the existing predictors in identifying subcellular locations of
      eukaryotic proteins.

PMID- 22629315
TI  - Transcriptome sequencing of and microarray development for a Helicoverpa zea cell
      line to investigate in vitro insect cell-baculovirus interactions.
AB  - The Heliothine insect complex contains some of the most destructive pests of
      agricultural crops worldwide, including the closely related Helicoverpa zea and
      H. armigera. Biological control using baculoviruses is practiced at a moderate
      level worldwide. In order to enable more wide spread use, a better understanding
      of cell-virus interactions is required. While many baculoviruses have been
      sequenced, none of the Heliothine insect genomes have been available. In this
      study, we sequenced, assembled and functionally annotated 29,586 transcripts from
      cultured H. zea cells using Illumina 100 bps and paired-end transcriptome
      sequencing (RNA-seq). The transcript sequences had high assembly coverage (64.5
      times). 23,401 sequences had putative protein functions, and over 13,000
      sequences had high similarities to available sequences in other insect species.
      The sequence database was estimated to cover at least 85% of all H. zea genes.
      The sequences were used to construct a microarray, which was evaluated on the
      infection of H. zea cells with H. Armigera single-capsid nucleopolyhedrovirus
      (HearNPV). The analysis revealed that up-regulation of apoptosis genes is the
      main cellular response in the early infection phase (18 hours post infection),
      while genes linked to four major immunological signalling pathways (Toll, IMD,
      Jak-STAT and JNK) were down-regulated. Only small changes (generally downwards)
      were observed for central carbon metabolism. The transcriptome and microarray
      platform developed in this study represent a greatly expanded resource base for
      H. zea insect-HearNPV interaction studies, in which key cellular pathways such as
      those for metabolism, immune response, transcription and replication have been
      identified. This resource will be used to develop better cell culture-based virus
      production processes, and more generally to investigate the molecular basis of
      host range and susceptibility, virus infectivity and virulence, and the ecology
      and evolution of baculoviruses.

PMID- 22629317
TI  - Deep brain stimulation of nucleus accumbens region in alcoholism affects reward
      processing.
AB  - The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus
      (NAcc) on the processing of reward in a gambling paradigm was investigated using
      H(2)[(15)O]-PET (positron emission tomography) in a 38-year-old man treated for
      severe alcohol addiction. Behavioral data analysis revealed a less risky, more
      careful choice behavior under active DBS compared to DBS switched off. PET showed
      win- and loss-related activations in the paracingulate cortex, temporal poles,
      precuneus and hippocampus under active DBS, brain areas that have been implicated
      in action monitoring and behavioral control. Except for the temporal pole these
      activations were not seen when DBS was deactivated. These findings suggest that
      DBS of the NAcc may act partially by improving behavioral control.

PMID- 22629316
TI  - Multi-ethnic analysis of lipid-associated loci: the NHLBI CARe project.
AB  - BACKGROUND: Whereas it is well established that plasma lipid levels have
      substantial heritability within populations, it remains unclear how many of the
      genetic determinants reported in previous studies (largely performed in European
      American cohorts) are relevant in different ethnicities. METHODOLOGY/PRINCIPAL
      FINDINGS: We tested a set of ~50,000 polymorphisms from ~2,000 candidate genes
      and genetic loci from genome-wide association studies (GWAS) for association with
      low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C), and triglycerides (TG) in 25,000 European Americans and 9,000 African
      Americans in the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene
      Association Resource (CARe). We replicated associations for a number of genes in
      one or both ethnicities and identified a novel lipid-associated variant in a
      locus harboring ICAM1. We compared the architecture of genetic loci associated
      with lipids in both African Americans and European Americans and found that the
      same genes were relevant across ethnic groups but the specific associated
      variants at each gene often differed. CONCLUSIONS/SIGNIFICANCE: We identify or
      provide further evidence for a number of genetic determinants of plasma lipid
      levels through population association studies. In many loci the determinants
      appear to differ substantially between African Americans and European Americans.

PMID- 22629319
TI  - Genome sizes and the Benford distribution.
AB  - BACKGROUND: Data on the number of Open Reading Frames (ORFs) coded by genomes
      from the 3 domains of Life show the presence of some notable general features.
      These include essential differences between the Prokaryotes and Eukaryotes, with
      the number of ORFs growing linearly with total genome size for the former, but
      only logarithmically for the latter. RESULTS: Simply by assuming that the
      (protein) coding and non-coding fractions of the genome must have different
      dynamics and that the non-coding fraction must be particularly versatile and
      therefore be controlled by a variety of (unspecified) probability distribution
      functions (pdf's), we are able to predict that the number of ORFs for Eukaryotes
      follows a Benford distribution and must therefore have a specific logarithmic
      form. Using the data for the 1000+ genomes available to us in early 2010, we find
      that the Benford distribution provides excellent fits to the data over several
      orders of magnitude. CONCLUSIONS: In its linear regime the Benford distribution
      produces excellent fits to the Prokaryote data, while the full non-linear form of
      the distribution similarly provides an excellent fit to the Eukaryote data.
      Furthermore, in their region of overlap the salient features are statistically
      congruent. This allows us to interpret the difference between Prokaryotes and
      Eukaryotes as the manifestation of the increased demand in the biological
      functions required for the larger Eukaryotes, to estimate some minimal genome
      sizes, and to predict a maximal Prokaryote genome size on the order of 8-12
      megabasepairs. These results naturally allow a mathematical interpretation in
      terms of maximal entropy and, therefore, most efficient information transmission.

PMID- 22629318
TI  - REDD1 protects osteoblast cells from gamma radiation-induced premature
      senescence.
AB  - Radiotherapy is commonly used for cancer treatment. However, it often results in
      side effects due to radiation damage in normal tissue, such as bone marrow (BM)
      failure. Adult hematopoietic stem and progenitor cells (HSPC) reside in BM next
      to the endosteal bone surface, which is lined primarily by hematopoietic niche
      osteoblastic cells. Osteoblasts are relatively more radiation-resistant than
      HSPCs, but the mechanisms are not well understood. In the present study, we
      demonstrated that the stress response gene REDD1 (regulated in development and
      DNA damage responses 1) was highly expressed in human osteoblast cell line (hFOB)
      cells after gamma irradiation. Knockdown of REDD1 with siRNA resulted in a
      decrease in hFOB cell numbers, whereas transfection of PCMV6-AC-GFP-REDD1 plasmid
      DNA into hFOB cells inhibited mammalian target of rapamycin (mTOR) and p21
      expression and protected these cells from radiation-induced premature senescence
      (PS). The PS in irradiated hFOB cells were characterized by significant
      inhibition of clonogenicity, activation of senescence biomarker SA-beta-gal, and
      the senescence-associated cytokine secretory phenotype (SASP) after 4 or 8 Gy
      irradiation. Immunoprecipitation assays demonstrated that the stress response
      proteins p53 and nuclear factor kappa B (NFkB) interacted with REDD1 in hFOB
      cells. Knockdown of NFkB or p53 gene dramatically suppressed REDD1 protein
      expression in these cells, indicating that REDD1 was regulated by both factors.
      Our data demonstrated that REDD1 is a protective factor in radiation-induced
      osteoblast cell premature senescence.

PMID- 22629320
TI  - Simple, fast and accurate implementation of the diffusion approximation algorithm
      for stochastic ion channels with multiple states.
AB  - BACKGROUND: The phenomena that emerge from the interaction of the stochastic
      opening and closing of ion channels (channel noise) with the non-linear neural
      dynamics are essential to our understanding of the operation of the nervous
      system. The effects that channel noise can have on neural dynamics are generally
      studied using numerical simulations of stochastic models. Algorithms based on
      discrete Markov Chains (MC) seem to be the most reliable and trustworthy, but
      even optimized algorithms come with a non-negligible computational cost.
      Diffusion Approximation (DA) methods use Stochastic Differential Equations (SDE)
      to approximate the behavior of a number of MCs, considerably speeding up
      simulation times. However, model comparisons have suggested that DA methods did
      not lead to the same results as in MC modeling in terms of channel noise
      statistics and effects on excitability. Recently, it was shown that the
      difference arose because MCs were modeled with coupled gating particles, while
      the DA was modeled using uncoupled gating particles. Implementations of DA with
      coupled particles, in the context of a specific kinetic scheme, yielded similar
      results to MC. However, it remained unclear how to generalize these
      implementations to different kinetic schemes, or whether they were faster than MC
      algorithms. Additionally, a steady state approximation was used for the
      stochastic terms, which, as we show here, can introduce significant inaccuracies.
      MAIN CONTRIBUTIONS: We derived the SDE explicitly for any given ion channel
      kinetic scheme. The resulting generic equations were surprisingly simple and
      interpretable--allowing an easy, transparent and efficient DA implementation,
      avoiding unnecessary approximations. The algorithm was tested in a voltage clamp
      simulation and in two different current clamp simulations, yielding the same
      results as MC modeling. Also, the simulation efficiency of this DA method
      demonstrated considerable superiority over MC methods, except when short time
      steps or low channel numbers were used.

PMID- 22629321
TI  - The roles of featural and configural face processing in snap judgments of sexual
      orientation.
AB  - Research has shown that people are able to judge sexual orientation from faces
      with above-chance accuracy, but little is known about how these judgments are
      formed. Here, we investigated the importance of well-established face processing
      mechanisms in such judgments: featural processing (e.g., an eye) and configural
      processing (e.g., spatial distance between eyes). Participants judged sexual
      orientation from faces presented for 50 milliseconds either upright, which
      recruits both configural and featural processing, or upside-down, when configural
      processing is strongly impaired and featural processing remains relatively
      intact. Although participants judged women's and men's sexual orientation with
      above-chance accuracy for upright faces and for upside-down faces, accuracy for
      upside-down faces was significantly reduced. The reduced judgment accuracy for
      upside-down faces indicates that configural face processing significantly
      contributes to accurate snap judgments of sexual orientation.

PMID- 22629322
TI  - Assessment and implication of prognostic imbalance in randomized controlled
      trials with a binary outcome--a simulation study.
AB  - BACKGROUND: Chance imbalance in baseline prognosis of a randomized controlled
      trial can lead to over or underestimation of treatment effects, particularly in
      trials with small sample sizes. Our study aimed to (1) evaluate the probability
      of imbalance in a binary prognostic factor (PF) between two treatment arms, (2)
      investigate the impact of prognostic imbalance on the estimation of a treatment
      effect, and (3) examine the effect of sample size (n) in relation to the first
      two objectives. METHODS: We simulated data from parallel-group trials evaluating
      a binary outcome by varying the risk of the outcome, effect of the treatment,
      power and prevalence of the PF, and n. Logistic regression models with and
      without adjustment for the PF were compared in terms of bias, standard error,
      coverage of confidence interval and statistical power. RESULTS: For a PF with a
      prevalence of 0.5, the probability of a difference in the frequency of the PF>=5%
      reaches 0.42 with 125/arm. Ignoring a strong PF (relative risk = 5) leads to
      underestimating the strength of a moderate treatment effect, and the
      underestimate is independent of n when n is >50/arm. Adjusting for such PF
      increases statistical power. If the PF is weak (RR = 2), adjustment makes little
      difference in statistical inference. Conditional on a 5% imbalance of a powerful
      PF, adjustment reduces the likelihood of large bias. If an absolute measure of
      imbalance >=5% is deemed important, including 1000 patients/arm provides
      sufficient protection against such an imbalance. Two thousand patients/arm may
      provide an adequate control against large random deviations in treatment effect
      estimation in the presence of a powerful PF. CONCLUSIONS: The probability of
      prognostic imbalance in small trials can be substantial. Covariate adjustment
      improves estimation accuracy and statistical power, and hence should be performed
      when strong PFs are observed.

PMID- 22629323
TI  - MicroRNA 10a marks regulatory T cells.
AB  - MicroRNAs (miRNAs) are crucial for regulatory T cell (Treg) stability and
      function. We report that microRNA-10a (miR-10a) is expressed in Tregs but not in
      other T cells including individual thymocyte subsets. Expression profiling in
      inbred mouse strains demonstrated that non-obese diabetic (NOD) mice with a
      genetic susceptibility for autoimmune diabetes have lower Treg-specific miR-10a
      expression than C57BL/6J autoimmune resistant mice. Inhibition of miR-10a
      expression in vitro leads to reduced FoxP3 expression levels and miR-10a
      expression is lower in unstable "exFoxP3" T cells. Unstable in vitro TGF-beta
      induced, iTregs do not express miR-10a unless cultured in the presence of
      retinoic acid (RA) which has been associated with increased stability of iTreg,
      suggesting that miR-10a might play a role in stabilizing Treg. However, genetic
      ablation of miR-10a neither affected the number and phenotype of natural Treg nor
      the capacity of conventional T cells to induce FoxP3 in response to TGFbeta, RA,
      or a combination of the two. Thus, miR-10a is selectively expressed in Treg but
      inhibition by antagomiRs or genetic ablation resulted in discordant effects on
      FoxP3.

PMID- 22629324
TI  - Extent of structural asymmetry in homodimeric proteins: prevalence and relevance.
AB  - Most homodimeric proteins have symmetric structure. Although symmetry is known to
      confer structural and functional advantage, asymmetric organization is also
      observed. Using a non-redundant dataset of 223 high-resolution crystal structures
      of biologically relevant homodimers, we address questions on the prevalence and
      significance of asymmetry. We used two measures to quantify global and interface
      asymmetry, and assess the correlation of several molecular and structural
      parameters with asymmetry. We have identified rare cases (11/223) of biologically
      relevant homodimers with pronounced global asymmetry. Asymmetry serves as a means
      to bring about 2:1 binding between the homodimer and another molecule; it also
      enables cellular signalling arising from asymmetric macromolecular ligands such
      as DNA. Analysis of these cases reveals two possible mechanisms by which possible
      infinite array formation is prevented. In case of homodimers associating via non
      topologically equivalent surfaces in their tertiary structures, ligand-dependent
      mechanisms are used. For stable dimers binding via large surfaces, ligand
      dependent structural change regulates polymerisation/depolymerisation; for
      unstable dimers binding via smaller surfaces that are not evolutionarily well
      conserved, dimerisation occurs only in the presence of the ligand. In case of
      homodimers associating via interaction surfaces with parts of the surfaces
      topologically equivalent in the tertiary structures, steric hindrance serves as
      the preventive mechanism of infinite array. We also find that homodimers
      exhibiting grossly symmetric organization rarely exhibit either perfect local
      symmetry or high local asymmetry. Binding of small ligands at the interface does
      not cause any significant variation in interface asymmetry. However,
      identification of biologically relevant interface asymmetry in grossly symmetric
      homodimers is confounded by the presence of similar small magnitude changes
      caused due to artefacts of crystallisation. Our study provides new insights
      regarding accommodation of asymmetry in homodimers.

PMID- 22629325
TI  - Psychophysics of a nociceptive test in the mouse: ambient temperature as a key
      factor for variation.
AB  - BACKGROUND: The mouse is increasingly used in biomedical research, notably in
      behavioral neurosciences for the development of tests or models of pain. Our goal
      was to provide the scientific community with an outstanding tool that allows the
      determination of psychophysical descriptors of a nociceptive reaction, which are
      inaccessible with conventional methods: namely the true threshold, true latency,
      conduction velocity of the peripheral fibers that trigger the response and
      latency of the central decision-making process. METHODOLOGY/PRINCIPAL FINDINGS:
      Basically, the procedures involved heating of the tail with a CO(2) laser,
      recording of tail temperature with an infrared camera and stopping the heating
      when the animal reacted. The method is based mainly on the measurement of three
      observable variables, namely the initial temperature, the heating rate and the
      temperature reached at the actual moment of the reaction following random
      variations in noxious radiant heat. The initial temperature of the tail, which
      itself depends on the ambient temperature, very markedly influenced the
      behavioral threshold, the behavioral latency and the conduction velocity of the
      peripheral fibers but not the latency of the central decision-making.
      CONCLUSIONS/SIGNIFICANCE: We have validated a psychophysical approach to
      nociceptive reactions for the mouse, which has already been described for rats
      and Humans. It enables the determination of four variables, which contribute to
      the overall latency of the response. The usefulness of such an approach was
      demonstrated by providing new fundamental findings regarding the influence of
      ambient temperature on nociceptive processes. We conclude by challenging the
      validity of using as "pain index" the reaction time of a behavioral response to
      an increasing heat stimulus and emphasize the need for a very careful control of
      the ambient temperature, as a prevailing environmental source of variation,
      during any behavioral testing of mice.

PMID- 22629326
TI  - Normalized lift: an energy interpretation of the lift coefficient simplifies
      comparisons of the lifting ability of rotating and flapping surfaces.
AB  - For a century, researchers have used the standard lift coefficient C(L) to
      evaluate the lift, L, generated by fixed wings over an area S against dynamic
      pressure, 1/2rhov(2), where v is the effective velocity of the wing. Because the
      lift coefficient was developed initially for fixed wings in steady flow, its
      application to other lifting systems requires either simplifying assumptions or
      complex adjustments as is the case for flapping wings and rotating cylinders.This
      paper interprets the standard lift coefficient of a fixed wing slightly
      differently, as the work exerted by the wing on the surrounding flow field
      (L/rho.S), compared against the total kinetic energy required for generating said
      lift, 1/2v(2). This reinterpreted coefficient, the normalized lift, is derived
      from the work-energy theorem and compares the lifting capabilities of dissimilar
      lift systems on a similar energy footing. The normalized lift is the same as the
      standard lift coefficient for fixed wings, but differs for wings with more
      complex motions; it also accounts for such complex motions explicitly and without
      complex modifications or adjustments. We compare the normalized lift with the
      previously-reported values of lift coefficient for a rotating cylinder in Magnus
      effect, a bat during hovering and forward flight, and a hovering dipteran.The
      maximum standard lift coefficient for a fixed wing without flaps in steady flow
      is around 1.5, yet for a rotating cylinder it may exceed 9.0, a value that
      implies that a rotating cylinder generates nearly 6 times the maximum lift of a
      wing. The maximum normalized lift for a rotating cylinder is 1.5. We suggest that
      the normalized lift can be used to evaluate propellers, rotors, flapping wings of
      animals and micro air vehicles, and underwater thrust-generating fins in the same
      way the lift coefficient is currently used to evaluate fixed wings.

PMID- 22629328
TI  - Phylogeny of basal iguanodonts (Dinosauria: Ornithischia): an update.
AB  - The precise phylogenetic relationships of many non-hadrosaurid members of
      Iguanodontia, i.e., basal iguanodonts, have been unclear. Therefore, to
      investigate the global phylogeny of basal iguanodonts a comprehensive data matrix
      was assembled, including nearly every valid taxon of basal iguanodont. The matrix
      was analyzed in the program TNT, and the maximum agreement subtree of the
      resulting most parsimonious trees was then calculated in PAUP. Ordering certain
      multistate characters and omitting taxa through safe taxonomic reduction did not
      markedly improve resolution. The results provide some new information on the
      phylogeny of basal iguanodonts, pertaining especially to obscure or recently
      described taxa, and support some recent taxonomic revisions, such as the
      splitting of traditional "Camptosaurus" and "Iguanodon". The maximum agreement
      subtree also shows a close relationship between the Asian Probactrosaurus
      gobiensis and the North American Eolambia, supporting the previous hypothesis of
      faunal interchange between Asia and North America in the early Late Cretaceous.
      Nevertheless, the phylogenetic relationships of many basal iguanodonts remain
      ambiguous due to the high number of taxa removed from the maximum agreement
      subtree and poor resolution of consensus trees.

PMID- 22629327
TI  - The metagenome of an anaerobic microbial community decomposing poplar wood chips.
AB  - This study describes the composition and metabolic potential of a lignocellulosic
      biomass degrading community that decays poplar wood chips under anaerobic
      conditions. We examined the community that developed on poplar biomass in a non
      aerated bioreactor over the course of a year, with no microbial inoculation other
      than the naturally occurring organisms on the woody material. The composition of
      this community contrasts in important ways with biomass-degrading communities
      associated with higher organisms, which have evolved over millions of years into
      a symbiotic relationship. Both mammalian and insect hosts provide partial size
      reduction, chemical treatments (low or high pH environments), and complex
      enzymatic 'secretomes' that improve microbial access to cell wall polymers. We
      hypothesized that in order to efficiently degrade coarse untreated biomass, a
      spontaneously assembled free-living community must both employ alternative
      strategies, such as enzymatic lignin depolymerization, for accessing
      hemicellulose and cellulose and have a much broader metabolic potential than host
      associated communities. This would suggest that such a community would make a
      valuable resource for finding new catalytic functions involved in biomass
      decomposition and gaining new insight into the poorly understood process of
      anaerobic lignin depolymerization. Therefore, in addition to determining the
      major players in this community, our work specifically aimed at identifying
      functions potentially involved in the depolymerization of cellulose,
      hemicelluloses, and lignin, and to assign specific roles to the prevalent
      community members in the collaborative process of biomass decomposition. A
      bacterium similar to Magnetospirillum was identified among the dominant community
      members, which could play a key role in the anaerobic breakdown of aromatic
      compounds. We suggest that these compounds are released from the lignin fraction
      in poplar hardwood during the decay process, which would point to lignin
      modification or depolymerization under anaerobic conditions.

PMID- 22629329
TI  - Center of excellence in research reporting in neurosurgery--diagnostic ontology.
AB  - MOTIVATION: Evidence-based medicine (EBM), in the field of neurosurgery, relies
      on diagnostic studies since Randomized Controlled Trials (RCTs) are uncommon.
      However, diagnostic study reporting is less standardized which increases the
      difficulty in reliably aggregating results. Although there have been several
      initiatives to standardize reporting, they have shown to be sub-optimal.
      Additionally, there is no central repository for storing and retrieving related
      articles. RESULTS: In our approach we formulate a computational diagnostic
      ontology containing 91 elements, including classes and sub-classes, which are
      required to conduct Systematic Reviews-Meta Analysis (SR-MA) for diagnostic
      studies, which will assist in standardized reporting of diagnostic articles. SR
      MA are studies that aggregate several studies to come to one conclusion for a
      particular research question. We also report high percentage of agreement among
      five observers as a result of the interobserver agreement test that we conducted
      among them to annotate 13 articles using the diagnostic ontology. Moreover, we
      extend our existing repository CERR-N to include diagnostic studies.
      AVAILABILITY: The ontology is available for download as an.owl file at:
      http://bioportal.bioontology.org/ontologies/3013.

PMID- 22629330
TI  - Immunogenicity and tolerability after two doses of non-adjuvanted, whole-virion
      pandemic influenza A (H1N1) vaccine in HIV-infected individuals.
AB  - BACKGROUND: During the influenza pandemic of 2009/10, the whole-virion, Vero-cell
      derived, inactivated, pandemic influenza A (H1N1) vaccine Celvapan(r) (Baxter)
      was used in Austria. Celvapan(r) is adjuvant-free and was the only such vaccine
      at that time in Europe. The objective of this observational, non-interventional,
      prospective single-center study was to evaluate the immunogenicity and
      tolerability of two intramuscular doses of this novel vaccine in HIV-positive
      individuals. METHODS AND FINDINGS: A standard hemagglutination inhibition (HAI)
      assay was used for evaluation of the seroconversion rate and seroprotection
      against the pandemic H1N1 strain. In addition, H1N1-specific IgG antibodies were
      measured using a recently developed ELISA and compared with the HAI results.
      Tolerability of vaccination was evaluated up to one month after the second dose.
      A total of 79 HIV-infected adults with an indication for H1N1 vaccination were
      evaluated. At baseline, 55 of the 79 participants had an HAI titer >=1:40 and two
      patients showed a positive IgG ELISA. The seroconversion rate was 31% after the
      first vaccination, increasing to 41% after the second; the corresponding
      seroprotection rates were 92% and 83% respectively. ELISA IgG levels were
      positive in 25% after the first vaccination and in 37% after the second. Among
      the participants with baseline HAI titers <1:40, 63% seroconverted. Young age was
      clearly associated with lower HAI titers at baseline and with higher
      seroconversion rates, whereas none of the seven patients >60 years of age had a
      baseline HAI titer <1:40 or seroconverted after vaccination. The vaccine was well
      tolerated. CONCLUSION: The non-adjuvanted pandemic influenza A (H1N1) vaccine was
      well tolerated and induced a measurable immune response in a sample of HIV
      infected individuals.

PMID- 22629331
TI  - Feasibility of prehospital teleconsultation in acute stroke--a pilot study in
      clinical routine.
AB  - BACKGROUND: Inter-hospital teleconsultation improves stroke care. To transfer
      this concept into the emergency medical service (EMS), the feasibility and
      effects of prehospital teleconsultation were investigated. METHODOLOGY/PRINCIPAL
      FINDINGS: Teleconsultation enabling audio communication, real-time video
      streaming, vital data and still picture transmission was conducted between an
      ambulance and a teleconsultation center. Pre-notification of the hospital was
      carried out with a 14-item stroke history checklist via e-mail-to-fax. Beside
      technical assessments possible influences on prehospital and initial in-hospital
      time intervals, prehospital diagnostic accuracy and the transfer of stroke
      specific data were investigated by comparing telemedically assisted prehospital
      care (telemedicine group) with local regular EMS care (control group). All
      prehospital stroke patients over a 5-month period were included during weekdays
      (7.30 a.m.-4.00 p.m.). In 3 of 18 missions partial dropouts of the system
      occurred; neurological co-evaluation via video transmission was conducted in 12
      cases. The stroke checklist was transmitted in 14 cases (78%). Telemedicine group
      (n = 18) vs. control group (n = 47): Prehospital time intervals were comparable,
      but in both groups the door to brain imaging times were longer than recommended
      (median 59.5 vs. 57.5 min, p = 0.6447). The prehospital stroke diagnosis was
      confirmed in 61% vs. 67%, p = 0.8451. Medians of 14 (IQR 9) vs. 5 (IQR 2) stroke
      specific items were transferred in written form to the in-hospital setting,
      p<0.0001. In 3 of 10 vs. 5 of 27 patients with cerebral ischemia thrombolytics
      were administered, p = 0.655. CONCLUSIONS: Teleconsultation was feasible but
      technical performance and reliability have to be improved. The approach led to
      better stroke specific information; however, a superiority over regular EMS care
      was not found and in-hospital time intervals were unacceptably long in both
      groups. The feasibility of prehospital tele-stroke consultation has future
      potential to improve emergency care especially when no highly trained personnel
      are on-scene. TRIAL REGISTRATION: International Standard Randomised Controlled
      Trial Number Register (ISRCTN) ISRCTN83270177.

PMID- 22629332
TI  - Validity and reliability of the strengths and difficulties questionnaire in 5-6
      year olds: differences by gender or by parental education?
AB  - INTRODUCTION: The Strengths and Difficulties Questionnaire (SDQ) is a relatively
      short instrument developed to detect psychosocial problems in children aged 3-16
      years. It addresses four dimensions: emotional problems, conduct problems,
      hyperactivity/inattention problems, peer problems that count up to the total
      difficulties score, and a fifth dimension; prosocial behaviour. The validity and
      reliability of the SDQ has not been fully investigated in younger age groups.
      Therefore, this study assesses the validity and reliability of the parent and
      teacher versions of the SDQ in children aged 5-6 years in the total sample, and
      in subgroups according to child gender and parental education level. METHODS: The
      SDQ was administered as part of the Dutch regularly provided preventive health
      check for children aged 5-6 years. Parents provided information on 4750 children
      and teachers on 4516 children. RESULTS: Factor analyses of the parent and teacher
      SDQ confirmed that the original five scales were present (parent RMSEA = 0.05;
      teacher RMSEA = 0.07). Interrater correlations between parents and teachers were
      small (ICCs of 0.21-0.44) but comparable to what is generally found for
      psychosocial problem assessments in children. These correlations were larger for
      males than for females. Cronbach's alphas for the total difficulties score were
      0.77 for the parent SDQ and 0.81 for the teacher SDQ. Four of the subscales on
      the parent SDQ and two of the subscales on the teacher SDQ had an alpha <0.70.
      Alphas were generally higher for male children and for low parental education
      level. DISCUSSION: The validity and reliability of the total difficulties score
      of the parent and teacher SDQ are satisfactory in all groups by informant, child
      gender, and parental education level. Our results support the use of the SDQ in
      younger age groups. However, some subscales are less reliable and we recommend
      only to use the total difficulties score for screening purposes.

PMID- 22629333
TI  - Silencing of the violaxanthin de-epoxidase gene in the diatom Phaeodactylum
      tricornutum reduces diatoxanthin synthesis and non-photochemical quenching.
AB  - Diatoms are a major group of primary producers ubiquitous in all aquatic
      ecosystems. To protect themselves from photooxidative damage in a fluctuating
      light climate potentially punctuated with regular excess light exposures, diatoms
      have developed several photoprotective mechanisms. The xanthophyll cycle (XC)
      dependent non-photochemical chlorophyll fluorescence quenching (NPQ) is one of
      the most important photoprotective processes that rapidly regulate photosynthesis
      in diatoms. NPQ depends on the conversion of diadinoxanthin (DD) into
      diatoxanthin (DT) by the violaxanthin de-epoxidase (VDE), also called DD de
      epoxidase (DDE). To study the role of DDE in controlling NPQ, we generated
      transformants of P. tricornutum in which the gene (Vde/Dde) encoding for DDE was
      silenced. RNA interference was induced by genetic transformation of the cells
      with plasmids containing either short (198 bp) or long (523 bp) antisense (AS)
      fragments or, alternatively, with a plasmid mediating the expression of a self
      complementary hairpin-like construct (inverted repeat, IR). The silencing
      approaches generated diatom transformants with a phenotype clearly
      distinguishable from wildtype (WT) cells, i.e. a lower degree as well as slower
      kinetics of both DD de-epoxidation and NPQ induction. Real-time PCR based
      quantification of Dde transcripts revealed differences in transcript levels
      between AS transformants and WT cells but also between AS and IR transformants,
      suggesting the possible presence of two different gene silencing mediating
      mechanisms. This was confirmed by the differential effect of the light intensity
      on the respective silencing efficiency of both types of transformants. The
      characterization of the transformants strengthened some of the specific features
      of the XC and NPQ and confirmed the most recent mechanistic model of the DT/NPQ
      relationship in diatoms.

PMID- 22629334
TI  - Concomitant pulmonary tuberculosis in hospitalized healthcare-associated
      pneumonia in a tuberculosis endemic area: a multi-center retrospective study.
AB  - BACKGROUND: In tuberculosis (TB) endemic areas, Mycobacterium tuberculosis is an
      important but easily misdiagnosed pathogen in community-acquired pneumonia (CAP).
      However, the occurrence of concomitant pulmonary tuberculosis (PTB) in
      hospitalized healthcare-associated pneumonia (HCAP) has never been investigated.
      METHODS AND FINDINGS: Seven hundred and one hospitalized HCAP and 934
      hospitalized CAP patients from six medical centers in Taiwan were included in
      this nationwide retrospective study. Concomitant PTB was defined as active PTB
      diagnosed within 60 days of admission due to HCAP or CAP. The predictors for
      concomitant PTB and the impact of PTB on the outcomes of pneumonia were
      investigated. Among the enrolled subjects, 21/701 (3%) of the HCAP patients and
      25/934 (2.7%) of the CAP patients were documented to have concomitant PTB. In
      multivariate analysis, a history of previous anti-TB treatment (OR = 5.84, 95%
      CI: 2.29-20.37 in HCAP; OR = 3.33, 95% CI: 1.09-10.22 in CAP) and escalated
      pneumonia severity index (PSI) scores (OR = 1.014, 95% CI: 1.002-1.026, in HCAP;
      OR = 1.013, 95% CI: 1.001-1.026, in CAP) were independent predictors for
      concomitant PTB in both CAP and HCAP patients. Regarding treatment outcomes, HCAP
      patients with concomitant PTB were associated with more acute respiratory failure
      within 48 hours of admission (47.6% vs. 22.6%, p = 0.008), higher intensive care
      unit admission rate (61.9% vs. 35.7%, p = 0.014), longer hospitalization (39.6+/
      34.1 vs. 23.7+/-27 days, p = 0.009), and higher in-hospital mortality (47.6% vs.
      26.3%, p = 0.03) than those without concomitant PTB. Exposure to certain groups
      of antibiotics for the treatment of pneumonia was not associated with the
      occurrence of concomitant PTB. CONCLUSIONS: In HCAP patients, the occurrence of
      concomitant PTB is comparable with that in CAP patients and associated with
      higher PSI scores, more acute respiratory failure, and higher in-hospital
      mortality.

PMID- 22629335
TI  - The baseline and longitudinal changes of PCC connectivity in mild cognitive
      impairment: a combined structure and resting-state fMRI study.
AB  - The baseline and longitudinal changes of the posterior cingulate cortex (PCC)
      connectivity were assessed in order to clarify the neural mechanism of mild
      cognitive impairment (MCI). Twenty-eight right-handed subjects (14 MCI patients
      and 14 healthy elders) participated in this study. Clinical and
      neuropsychological examinations were performed on all the subjects. PCC
      functional connectivity was studied by examining the correlation between low
      frequency fMRI signal fluctuations in the PCC and those in all the other brain
      regions. Additionally, we traced all the MCI patients and compared their PCC
      connectivity in the initial stage and that in 3 years later. We also explored the
      relationship between the PCC functional connectivity strength and cognitive
      performances. Our results are as follows: Functional connectivity between the PCC
      and a set of regions is decreased in MCI patients. Most of these regions are
      within the default mode network (DMN). Three years later, the regions of superior
      frontal gyrus (SFG) and middle frontal gyrus (MFG) presented further decreased
      connectivity to the PCC in MCI. In addition, we also find enhanced functional
      connectivity between PCC and medial prefrontal cortex (MPFC), PCC and anterior
      cingulate cortex (ACC) in MCI patients. At last, our research also shows that the
      PCC connectivity with some regions significantly correlates with the cognitive
      performances of patients as measured by mini-mental state examination (MMSE), and
      California verbal learning test (CVLT) scores. The baseline and longitudinal
      changes of the PCC connectivity in our study suggest that impairment and
      compensation coexist in the disease progress of MCI patients.

PMID- 22629336
TI  - Algal toxins alter copepod feeding behavior.
AB  - Using digital holographic cinematography, we quantify and compare the feeding
      behavior of free-swimming copepods, Acartia tonsa, on nutritional prey
      (Storeatula major) to that occurring during exposure to toxic and non-toxic
      strains of Karenia brevis and Karlodinium veneficum. These two harmful algal
      species produce polyketide toxins with different modes of action and potency. We
      distinguish between two different beating modes of the copepod's feeding
      appendages-a "sampling beating" that has short durations (<100 ms) and involves
      little fluid entrainment and a longer duration "grazing beating" that persists up
      to 1200 ms and generates feeding currents. The durations of both beating modes
      have log-normal distributions. Without prey, A. tonsa only samples the
      environment at low frequency. Upon introduction of non-toxic food, it increases
      its sampling time moderately and the grazing period substantially. On mono algal
      diets for either of the toxic dinoflagellates, sampling time fraction is high but
      the grazing is very limited. A. tonsa demonstrates aversion to both toxic algal
      species. In mixtures of S. major and the neurotoxin producing K. brevis, sampling
      and grazing diminish rapidly, presumably due to neurological effects of consuming
      brevetoxins while trying to feed on S. major. In contrast, on mixtures of
      cytotoxin producing K. veneficum, both behavioral modes persist, indicating that
      intake of karlotoxins does not immediately inhibit the copepod's grazing
      behavior. These findings add critical insight into how these algal toxins may
      influence the copepod's feeding behavior, and suggest how some harmful algal
      species may alter top-down control exerted by grazers like copepods.

PMID- 22629337
TI  - Emergence and prevalence of human vector-borne diseases in sink vector
      populations.
AB  - Vector-borne diseases represent a major public health concern in most tropical
      and subtropical areas, and an emerging threat for more developed countries. Our
      understanding of the ecology, evolution and control of these diseases relies
      predominantly on theory and data on pathogen transmission in large self
      sustaining 'source' populations of vectors representative of highly endemic
      areas. However, there are numerous places where environmental conditions are less
      favourable to vector populations, but where immigration allows them to persist.
      We built an epidemiological model to investigate the dynamics of six major human
      vector borne-diseases in such non self-sustaining 'sink' vector populations. The
      model was parameterized through a review of the literature, and we performed
      extensive sensitivity analysis to look at the emergence and prevalence of the
      pathogen that could be encountered in these populations. Despite the low vector
      abundance in typical sink populations, all six human diseases were able to spread
      in 15-55% of cases after accidental introduction. The rate of spread was much
      more strongly influenced by vector longevity, immigration and feeding rates, than
      by transmission and virulence of the pathogen. Prevalence in humans remained
      lower than 5% for dengue, leishmaniasis and Japanese encephalitis, but
      substantially higher for diseases with longer duration of infection; malaria and
      the American and African trypanosomiasis. Vector-related parameters were again
      the key factors, although their influence was lower than on pathogen emergence.
      Our results emphasize the need for ecology and evolution to be thought in the
      context of metapopulations made of a mosaic of sink and source habitats, and to
      design vector control program not only targeting areas of high vector density,
      but working at a larger spatial scale.

PMID- 22629338
TI  - Microsatellite and mitochondrial data provide evidence for a single major
      introduction for the Neartic leafhopper Scaphoideus titanus in Europe.
AB  - Scaphoideus titanus, a leafhopper native to North America and invasive in Europe,
      is the vector of the Flavescence doree phytoplasma, the causal agent of the most
      important form of grapevine yellows in European vineyards. We studied 10
      polymorphic microsatellite loci and a 623 bp fragment of the mitochondrial
      cytochrome oxidase II gene in native S. titanus from north-eastern America and
      introduced European populations, to elucidate the colonization scenario.
      Consistent with their recent history, invasive European populations were less
      genetically diverse than American populations for both types of markers,
      suggesting a recent bottleneck. Significant isolation by distance was detected
      between American populations but not between European populations. None of the
      European mitochondrial haplotypes was found in the American vineyards, from which
      they are assumed to have originated. The precise source of the invasive S.
      titanus populations therefore remains unclear. Nevertheless, the high
      heterozygosity of North-East American populations (which contained 92% of the
      observed alleles) suggests that this region is part of the native range of S.
      titanus. Clustering population genetics analyses with microsatellite and
      mitochondrial data suggested that European populations originated from a single
      introduction event. Most of the introduced populations clustered with populations
      from Long Island, the Atlantic Coast winegrowing region in which Vitis aestivalis
      occurs.

PMID- 22629339
TI  - Prevalence of anxiety and depression among outpatients with type 2 diabetes in
      the Mexican population.
AB  - BACKGROUND: Depression and anxiety are common in diabetic patients; however, in
      recent years the frequency of these symptoms has markedly increased worldwide.
      Therefore, it is necessary to establish the frequency and factors associated with
      depression and anxiety, since they can be responsible for premature morbidity,
      mortality, risk of developing comorbidities, complications, suffering of
      patients, as well as escalation of costs. We studied the frequency of depression
      and anxiety in Mexican outpatients with type 2 diabetes and identified the risk
      factors for depression and anxiety. METHODS AND FINDINGS: We performed a study in
      820 patients with type 2 diabetes. The prevalence of depression and anxiety was
      estimated using the Hamilton Depression Rating Scale and the Hamilton Anxiety
      Rating Scale, respectively. We calculated the proportions for depression and
      anxiety and, after adjusting for confounding variables, we performed multivariate
      analysis using multiple logistic regressions to evaluate the combined effect of
      the various factors associated with anxiety and depression among persons with
      type 2 diabetes. The rates for depression and anxiety were 48.27% (95% CI: 44.48
      52.06) and 55.10% (95% CI: 51.44-58.93), respectively. Occupation and
      complications in diabetes were the factors associated with anxiety, whereas
      glucose level and complications in diabetes were associated with depression.
      Complications in diabetes was a factor common to depression and anxiety
      (p<0.0001; OR 1.79, 95% CI 1.29-2.4). CONCLUSIONS: Our findings demonstrate that
      a large proportion of diabetic patients present depression and/or anxiety. We
      also identified a significant association between complications in diabetes with
      depression and anxiety. Interventions are necessary to hinder the appearance of
      complications in diabetes and in consequence prevent depression and anxiety.

PMID- 22629340
TI  - Actin- and dynamin-dependent maturation of bulk endocytosis restores
      neurotransmission following synaptic depletion.
AB  - Bulk endocytosis contributes to the maintenance of neurotransmission at the
      amphibian neuromuscular junction by regenerating synaptic vesicles. How nerve
      terminals internalize adequate portions of the presynaptic membrane when bulk
      endocytosis is initiated before the end of a sustained stimulation is unknown. A
      maturation process, occurring at the end of the stimulation, is hypothesised to
      precisely restore the pools of synaptic vesicles. Using confocal time-lapse
      microscopy of FM1-43-labeled nerve terminals at the amphibian neuromuscular
      junction, we confirm that bulk endocytosis is initiated during a sustained
      tetanic stimulation and reveal that shortly after the end of the stimulation,
      nerve terminals undergo a maturation process. This includes a transient bulging
      of the plasma membrane, followed by the development of large intraterminal FM1-43
      positive donut-like structures comprising large bulk membrane cisternae
      surrounded by recycling vesicles. The degree of bulging increased with
      stimulation frequency and the plasmalemma surface retrieved following the
      transient bulging correlated with the surface membrane internalized in bulk
      cisternae and recycling vesicles. Dyngo-4a, a potent dynamin inhibitor, did not
      block the initiation, but prevented the maturation of bulk endocytosis. In
      contrast, cytochalasin D, an inhibitor of actin polymerization, hindered both the
      initiation and maturation processes. Both inhibitors hampered the functional
      recovery of neurotransmission after synaptic depletion. Our data confirm that
      initiation of bulk endocytosis occurs during stimulation and demonstrates that a
      delayed maturation process controlled by actin and dynamin underpins the coupling
      between exocytosis and bulk endocytosis.

PMID- 22629342
TI  - Adhesion forces and coaggregation between vaginal staphylococci and lactobacilli.
AB  - Urogenital infections are the most common ailments afflicting women. They are
      treated with dated antimicrobials whose efficacy is diminishing. The process of
      infection involves pathogen adhesion and displacement of indigenous Lactobacillus
      crispatus and Lactobacillus jensenii. An alternative therapeutic approach to
      antimicrobial therapy is to reestablish lactobacilli in this microbiome through
      probiotic administration. We hypothesized that lactobacilli displaying strong
      adhesion forces with pathogens would facilitate coaggregation between the two
      strains, ultimately explaining the elimination of pathogens seen in vivo. Using
      atomic force microscopy, we found that adhesion forces between lactobacilli and
      three virulent toxic shock syndrome toxin 1-producing Staphylococcus aureus
      strains, were significantly stronger (2.2-6.4 nN) than between staphylococcal
      pairs (2.2-3.4 nN), especially for the probiotic Lactobacillus reuteri RC-14 (4.0
      6.4 nN) after 120 s of bond-strengthening. Moreover, stronger adhesion forces
      resulted in significantly larger coaggregates. Adhesion between the bacteria
      occurred instantly upon contact and matured within one to two minutes,
      demonstrating the potential for rapid anti-pathogen effects using a probiotic.
      Coaggregation is one of the recognized mechanisms through which lactobacilli can
      exert their probiotic effects to create a hostile micro-environment around a
      pathogen. With antimicrobial options fading, it therewith becomes increasingly
      important to identify lactobacilli that bind strongly with pathogens.

PMID- 22629341
TI  - Evaluating fidelity in home-visiting programs a qualitative analysis of 1058 home
      visit case notes from 105 families.
AB  - OBJECTIVE: Implementation fidelity is a key issue in home-visiting programs as it
      determines a program's effectiveness in accomplishing its original goals. This
      paper seeks to evaluate fidelity in a 27-month program addressing maternal and
      child health which took place in France between 2006 and 2011. METHOD: To
      evaluate implementation fidelity, home visit case notes were analyzed using
      thematic qualitative and computer-assisted linguistic analyses. RESULTS: During
      the prenatal period, home visitors focused on the social components of the
      program. Visitors discussed the physical changes in pregnancy, and psychological
      and social environment issues. Discussing immigration, unstable employment and
      financial related issues, family relationships and dynamics and maternity
      services, while not expected, were found in case notes. Conversely, health during
      pregnancy, early child development and postpartum mood changes were not
      identified as topics within the prenatal case notes. During the postnatal period,
      most components of the intervention were addressed: home visitors observed the
      mother's adaptation to the baby; routine themes such as psychological needs and
      medical-social networks were evaluated; information on the importance of social
      support and on adapting the home environment was given; home visitors counseled
      on parental authority, and addressed mothers' self-esteem issues; finally, they
      helped to find child care, when necessary. Some themes were not addressed or
      partially addressed: health education, child development, home environment,
      mother's education plans and personal routine, partner support and play with the
      child. Other themes were not expected, but found in the case notes: social
      issues, mother-family relationship, relation with services, couple issues,
      quality of maternal behavior and child's language development. CONCLUSIONS: In
      this program, home visitors experienced difficulties addressing some of the
      objectives because they gave precedence to the families' urgent needs. This
      research stresses the importance of training home visitors to adapt the
      intervention to the social, psychological and health needs of families.

PMID- 22629343
TI  - Coral-bacterial communities before and after a coral mass spawning event on
      Ningaloo Reef.
AB  - Bacteria associated with three coral species, Acropora tenuis, Pocillopora
      damicornis and Tubastrea faulkneri, were assessed before and after coral mass
      spawning on Ningaloo Reef in Western Australia. Two colonies of each species were
      sampled before and after the mass spawning event and two additional samples were
      collected for P. damicornis after planulation. A variable 470 bp region of the 16
      S rRNA gene was selected for pyrosequencing to provide an understanding of
      potential variations in coral-associated bacterial diversity and community
      structure. Bacterial diversity increased for all coral species after spawning as
      assessed by Chao1 diversity indicators. Minimal changes in community structure
      were observed at the class level and data at the taxonomical level of genus
      incorporated into a PCA analysis indicated that despite bacterial diversity
      increasing after spawning, coral-associated community structure did not shift
      greatly with samples grouped according to species. However, interesting changes
      could be detected from the dataset; for example, alpha-Proteobacteria increased
      in relative abundance after coral spawning and particularly the Roseobacter clade
      was found to be prominent in all coral species, indicating that this group may be
      important in coral reproduction.

PMID- 22629344
TI  - Macrophages help NK cells to attack tumor cells by stimulatory NKG2D ligand but
      protect themselves from NK killing by inhibitory ligand Qa-1.
AB  - Natural killer (NK) cells and their crosstalk with other immune cells are
      important for innate immunity against tumor. To explore the role of the
      interaction between NK cells and macrophages in the regulation of anti-tumor
      activities of NK cells, we here demonstrate that poly I:C-treated macrophages
      increased NK cell-mediated cytotoxicity against target tumor cells in NKG2D
      dependent manner. In addition, IL-15, IL-18, and IFN-beta secreted by poly I:C
      treated macrophages are also involved in NKG2D expression and NK cell activation.
      Interestingly, the increase in expression of NKG2D ligands on macrophages induced
      a highly NK cell-mediated cytotoxicity against tumor cells, but not against
      macrophages themselves. Notably, a high expression level of Qa-1, a NKG2A ligand,
      on macrophages may contribute to such protection of macrophages from NK cell
      mediated killing. Furthermore, Qa-1 or NKG2A knockdown and Qa-1 antibody blockade
      caused the macrophages to be sensitive to NK cytolysis. These results suggested
      that macrophages may activate NK cells to attack tumor by NKG2D recognition
      whereas macrophages protect themselves from NK lysis via preferential expression
      of Qa-1.

PMID- 22629345
TI  - Sympathetic activation and baroreflex function during intradialytic hypertensive
      episodes.
AB  - BACKGROUND: The mechanisms of intradialytic increases in blood pressure are not
      well defined. The present study was undertaken to assess the role of autonomic
      nervous system activation during intradialytic hypertensive episodes.
      METHODOLOGY/PRINCIPAL FINDINGS: Continuous interbeat intervals (IBI) and systolic
      blood pressure (SBP) were monitored during hemodialysis in 108 chronic patients.
      Intradialytic hypertensive episodes defined as a period of at least 10 mmHg
      increase in SBP between the beginning and the end of a dialysis session or
      hypertension resistant to ultrafiltration occurring during or immediately after
      the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP
      variability, IBI variability and baroreceptor sensitivity (BRS) in the low (LF)
      and high (HF) frequency ranges were assessed using the complex demodulation
      technique (CDM). Intradialytic hypertensive episodes were associated with an
      increased (n = 45) or decreased (n = 17) heart rate. The maximal blood pressure
      was similar in both groups. In patients with increased heart rate the increase in
      blood pressure was associated with marked increases in SBP and IBI variability,
      with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in
      those with decreased heart rate, there were no significant changes in the above
      parameters. End-of-dialysis blood pressure in all sessions associated with
      hypertensive episode was significantly higher than in those without such
      episodes. In logistic regression analysis, predialysis BRS in the low frequency
      range was found to be the main predictor of intradialytic hypertension.
      CONCLUSION/SIGNIFICANCE: Our data point to sympathetic overactivity with feed
      forward blood pressure enhancement as an important mechanism of intradialytic
      hypertension in a significant proportion of patients. The triggers of increased
      sympathetic activity during hemodialysis remain to be determined. Intradialytic
      hypertensive episodes are associated with higher end-of-dialysis blood pressure,
      suggesting that intradialytic hypertension may play a role in generation of
      interdialytic hypertension.

PMID- 22629346
TI  - arrayMap: a reference resource for genomic copy number imbalances in human
      malignancies.
AB  - BACKGROUND: The delineation of genomic copy number abnormalities (CNAs) from
      cancer samples has been instrumental for identification of tumor suppressor genes
      and oncogenes and proven useful for clinical marker detection. An increasing
      number of projects have mapped CNAs using high-resolution microarray based
      techniques. So far, no single resource does provide a global collection of
      readily accessible oncogenomic array data. METHODOLOGY/PRINCIPAL FINDINGS: We
      here present arrayMap, a curated reference database and bioinformatics resource
      targeting copy number profiling data in human cancer. The arrayMap database
      provides a platform for meta-analysis and systems level data integration of high
      resolution oncogenomic CNA data. To date, the resource incorporates more than
      40,000 arrays in 224 cancer types extracted from several resources, including the
      NCBI's Gene Expression Omnibus (GEO), EBI's ArrayExpress (AE), The Cancer Genome
      Atlas (TCGA), publication supplements and direct submissions. For the majority of
      the included datasets, probe level and integrated visualization facilitate gene
      level and genome wide data review. Results from multi-case selections can be
      connected to downstream data analysis and visualization tools.
      CONCLUSIONS/SIGNIFICANCE: To our knowledge, currently no data source provides an
      extensive collection of high resolution oncogenomic CNA data which readily could
      be used for genomic feature mining, across a representative range of cancer
      entities. arrayMap represents our effort for providing a long term platform for
      oncogenomic CNA data independent of specific platform considerations or specific
      project dependence. The online database can be accessed at
      http//www.arraymap.org.

PMID- 22629348
TI  - Inferring biological structures from super-resolution single molecule images
      using generative models.
AB  - Localization-based super resolution imaging is presently limited by sampling
      requirements for dynamic measurements of biological structures. Generating an
      image requires serial acquisition of individual molecular positions at sufficient
      density to define a biological structure, increasing the acquisition time.
      Efficient analysis of biological structures from sparse localization data could
      substantially improve the dynamic imaging capabilities of these methods. Using a
      feature extraction technique called the Hough Transform simple biological
      structures are identified from both simulated and real localization data. We
      demonstrate that these generative models can efficiently infer biological
      structures in the data from far fewer localizations than are required for
      complete spatial sampling. Analysis at partial data densities revealed efficient
      recovery of clathrin vesicle size distributions and microtubule orientation
      angles with as little as 10% of the localization data. This approach
      significantly increases the temporal resolution for dynamic imaging and provides
      quantitatively useful biological information.

PMID- 22629347
TI  - Diversity effects on productivity are stronger within than between trophic groups
      in the arbuscular mycorrhizal symbiosis.
AB  - BACKGROUND: The diversity of plants and arbuscular mycorrhizal fungi (AMF) has
      been experimentally shown to alter plant and AMF productivity. However, little is
      known about how plant and AMF diversity interact to shape their respective
      productivity. METHODOLOGY/PRINCIPAL FINDINGS: We co-manipulated the diversity of
      both AMF and plant communities in two greenhouse studies to determine whether the
      productivity of each trophic group is mainly influenced by plant or AMF
      diversity, respectively, and whether there is any interaction between plant and
      fungal diversity. In both experiments we compared the productivity of three
      different plant species monocultures, or their respective 3-species mixtures.
      Similarly, in both studies these plant treatments were crossed with an AMF
      diversity gradient that ranged from zero (non-mycorrhizal controls) to a maximum
      of three and five taxonomically distinct AMF taxa, respectively. We found that
      within both trophic groups productivity was significantly influenced by taxon
      identity, and increased with taxon richness. These main effects of AMF and plant
      diversity on their respective productivities did not depend on each other, even
      though we detected significant individual taxon effects across trophic groups.
      CONCLUSIONS/SIGNIFICANCE: Our results indicate that similar ecological processes
      regulate diversity-productivity relationships within trophic groups. However,
      productivity-diversity relationships are not necessarily correlated across
      interacting trophic levels, leading to asymmetries and possible biotic feedbacks.
      Thus, biotic interactions within and across trophic groups should be considered
      in predictive models of community assembly.

PMID- 22629349
TI  - Occurrence patterns of Afrotropical ticks (Acari: Ixodidae) in the climate space
      are not correlated with their taxonomic relationships.
AB  - Foci of tick species occur at large spatial scales. They are intrinsically
      difficult to detect because the effect of geographical factors affecting
      conceptual influence of climate gradients. Here we use a large dataset of
      occurrences of ticks in the Afrotropical region to outline the main associations
      of those tick species with the climate space. Using a principal components
      reduction of monthly temperature and rainfall values over the Afrotropical
      region, we describe and compare the climate spaces of ticks in a gridded climate
      space. The dendrogram of distances among taxa according to occurrences in the
      climate niche is used to draw functional groups, or clusters of species with
      similar occurrences in the climate space, as different from morphologically
      derived (taxonomical) groups. We aim to further define the drivers of species
      richness and endemism at such a grid as well as niche similarities (climate space
      overlap) among species. Groups of species, as defined from morphological traits
      alone, are uncorrelated with functional clusters. Taxonomically related species
      occur separately in the climate gradients. Species belonging to the same
      functional group share more niche among them than with species in other
      functional groups. However, niche equivalency is also low for species within the
      same taxonomic cluster. Thus, taxa evolving from the same lineage tend to
      maximize the occupancy of the climate space and avoid overlaps with other species
      of the same taxonomic group. Richness values are drawn across the gradient of
      seasonal variation of temperature, higher values observed in a portion of the
      climate space with low thermal seasonality. Richness and endemism values are
      weakly correlated with mean values of temperature and rainfall. The most
      parsimonious explanation for the different taxonomic groups that exhibit common
      patterns of climate space subdivision is that they have a shared biogeographic
      history acting over a group of ancestrally co-distributed organisms.

PMID- 22629351
TI  - Negative priming under rapid serial visual presentation.
AB  - Negative priming (NP) was examined under a new paradigm wherein a target and
      distractors were temporally separated using rapid serial visual presentation
      (RSVP). The results from the two experiments revealed that (a) NP was robust
      under RSVP, such that the responses to a target were slower when the target
      served as a distractor in a previous trial than when it did not; (b) NP was found
      regardless of whether the distractors appeared before or after the targets; and
      (c) NP was stronger when the distractor was more distinctive. These findings are
      generally similar to those on NP in the spatial search task. The implications for
      the processes causing NP under RSVP are discussed in the current paper.

PMID- 22629350
TI  - Interferon-alpha improves phosphoantigen-induced Vgamma9Vdelta2 T-cells
      interferon-gamma production during chronic HCV infection.
AB  - In chronic HCV infection, treatment failure and defective host immune response
      highly demand improved therapy strategies. Vgamma9Vdelta2 T-cells may inhibit HCV
      replication in vitro through IFN-gamma release after Phosphoantigen (PhAg)
      stimulation. The aim of our work was to analyze Vgamma9Vdelta2 T-cell
      functionality during chronic HCV infection, studying the role of IFN-alpha on
      their function capability. IFN-gamma production by Vgamma9Vdelta2 T-cells was
      analyzed in vitro in 24 HCV-infected patients and 35 healthy donors (HD) after
      PhAg stimulation with or without IFN-alpha. The effect of in vivo PhAg/IFN-alpha
      administration on plasma IFN-gamma levels was analyzed in M. fascicularis
      monkeys. A quantitative analysis of IFN-gamma mRNA level and stability in
      Vgamma9Vdelta2 T-cells was also evaluated. During chronic HCV infection,
      Vgamma9Vdelta2 T-cells showed an effector/activated phenotype and were
      significantly impaired in IFN-gamma production. Interestingly, IFN-alpha was able
      to improve their IFN-gamma response to PhAg both in vitro in HD and HCV-infected
      patients, and in vivo in Macaca fascicularis primates. Finally, IFN-alpha
      increased IFN-gamma-mRNA transcription and stability in PhAg-activated
      Vgamma9Vdelta2 T-cells. Altogether our results show a functional impairment of
      Vgamma9Vdelta2 T-cells during chronic HCV infection that can be partially
      restored by using IFN-alpha. A study aimed to evaluate the antiviral impact of
      PhAg/IFN-alpha combination may provide new insight in designing possible combined
      strategies to improve HCV infection treatment outcome.

PMID- 22629352
TI  - Stochastic frontier model approach for measuring stock market efficiency with
      different distributions.
AB  - The stock market is considered essential for economic growth and expected to
      contribute to improved productivity. An efficient pricing mechanism of the stock
      market can be a driving force for channeling savings into profitable investments
      and thus facilitating optimal allocation of capital. This study investigated the
      technical efficiency of selected groups of companies of Bangladesh Stock Market
      that is the Dhaka Stock Exchange (DSE) market, using the stochastic frontier
      production function approach. For this, the authors considered the Cobb-Douglas
      Stochastic frontier in which the technical inefficiency effects are defined by a
      model with two distributional assumptions. Truncated normal and half-normal
      distributions were used in the model and both time-variant and time-invariant
      inefficiency effects were estimated. The results reveal that technical efficiency
      decreased gradually over the reference period and that truncated normal
      distribution is preferable to half-normal distribution for technical inefficiency
      effects. The value of technical efficiency was high for the investment group and
      low for the bank group, as compared with other groups in the DSE market for both
      distributions in time-varying environment whereas it was high for the investment
      group but low for the ceramic group as compared with other groups in the DSE
      market for both distributions in time-invariant situation.

PMID- 22629353
TI  - Improving oral hygiene skills by computer-based training: a randomized controlled
      comparison of the modified Bass and the Fones techniques.
AB  - BACKGROUND: Gingivitis and other plaque-associated diseases have a high
      prevalence in western communities even though the majority of adults report daily
      oral hygiene. This indicates a lack of oral hygiene skills. Currently, there is
      no clear evidence as to which brushing technique would bring about the best oral
      hygiene skills. While the modified Bass technique is often recommended by
      dentists and in textbooks, the Fones technique is often recommended in patient
      brochures. Still, standardized comparisons of the effectiveness of teaching these
      techniques are lacking. METHODOLOGY/PRINCIPAL FINDINGS: In a final sample of n =
      56 students, this multidisciplinary, randomized, examiner-blinded, controlled
      study compared the effects of parallel and standardized interactive computer
      presentations teaching either the Fones or the modified Bass technique. A control
      group was taught the basics of tooth brushing alone. Oral hygiene skills
      (remaining plaque after thorough oral hygiene) and gingivitis were assessed at
      baseline and 6, 12, and 28 weeks after the intervention. We found a significant
      group*time interaction for gingivitis (F(4/102) = 3.267; p = 0.016; epsilon =
      0.957; eta(2) = 0.114) and a significant main effect of group for oral hygiene
      skills (F(2/51) = 7.088; p = 0.002; eta(2) = 0.218). Fones was superior to Bass;
      Bass did not differ from the control group. Group differences were most prominent
      after 6 and 12 weeks. CONCLUSIONS/SIGNIFICANCE: The present trial indicates an
      advantage of teaching the Fones as compared to the modified Bass technique with
      respect to oral hygiene skills and gingivitis. Future studies are needed to
      analyze whether the disadvantage of teaching the Bass technique observed here is
      restricted to the teaching method employed. TRIAL REGISTRATION: German Clinical
      Trials Register DRKS00003488.

PMID- 22629354
TI  - Stereochemical insignificance discovered in Acinetobacter baumannii quorum
      sensing.
AB  - Stereochemistry is a key aspect of molecular recognition for biological systems.
      As such, receptors and enzymes are often highly stereospecific, only recognizing
      one stereoisomer of a ligand. Recently, the quorum sensing signaling molecules
      used by the nosocomial opportunistic pathogen, Acinetobacter baumannii, were
      identified, and the primary signaling molecule isolated from this species was N
      (3-hydroxydodecanoyl)-L-homoserine lactone. A plethora of bacterial species have
      been demonstrated to utilize 3-hydroxy-acylhomoserine lactone autoinducers, and
      in virtually all cases, the (R)-stereoisomer was identified as the natural ligand
      and exhibited greater autoinducer activity than the corresponding (S)
      stereoisomer. Using chemical synthesis and biochemical assays, we have uncovered
      a case of stereochemical insignificance in A. baumannii and provide a unique
      example where stereochemistry appears nonessential for acylhomoserine lactone
      mediated quorum sensing signaling. Based on previously reported phylogenetic
      studies, we suggest that A. baumannii has evolutionarily adopted this unique, yet
      promiscuous quorum sensing system to ensure its survival, particularly in the
      presence of other proteobacteria.

PMID- 22629355
TI  - Miscarriage, preterm delivery, and stillbirth: large variations in rates within a
      cohort of Australian women.
AB  - OBJECTIVES: We aimed to use simple clinical questions to group women and provide
      their specific rates of miscarriage, preterm delivery, and stillbirth for
      reference. Further, our purpose was to describe who has experienced particularly
      low or high rates of each event. METHODS: Data were collected as part of the
      Australian Longitudinal Study on Women's Health, a national prospective cohort.
      Reproductive histories were obtained from 5806 women aged 31-36 years in 2009,
      who had self-reported an outcome for one or more pregnancy. Age at first birth,
      number of live births, smoking status, fertility problems, use of in vitro
      fertilisation (IVF), education and physical activity were the variables that best
      separated women into groups for calculating the rates of miscarriage, preterm
      delivery, and stillbirth. RESULTS: Women reported 10,247 live births, 2544
      miscarriages, 1113 preterm deliveries, and 113 stillbirths. Miscarriage was
      correlated with stillbirth (r = 0.09, P<0.001). The calculable rate of
      miscarriage ranged from 11.3 to 86.5 miscarriages per 100 live births. Women who
      had high rates of miscarriage typically had fewer live births, were more likely
      to smoke and were more likely to have tried unsuccessfully to conceive for >=12
      months. The highest proportion of live preterm delivery (32.2%) occurred in women
      who had one live birth, had tried unsuccessfully to conceive for >=12 months, had
      used IVF, and had 12 years education or equivalent. Women aged 14-19.99 years at
      their first birth and reported low physical activity had 38.9 stillbirths per
      1000 live births, compared to the lowest rate at 5.5 per 1000 live births.
      CONCLUSION: Different groups of women experience vastly different rates of each
      adverse pregnancy event. We have used simple questions and established reference
      data that will stratify women into low- and high-rate groups, which may be useful
      in counselling those who have experienced miscarriage, preterm delivery, or
      stillbirth, plus women with fertility intent.

PMID- 22629356
TI  - Outcomes of comprehensive care for children empirically treated for multidrug
      resistant tuberculosis in a setting of high HIV prevalence.
AB  - BACKGROUND: Few studies have examined outcomes for children treated for multidrug
      resistant tuberculosis (MDR-TB), including those receiving concomitant treatment
      for MDR-TB and HIV co-infection. In Lesotho, where the adult HIV seroprevalence
      is estimated to be 24%, we sought to measure outcomes and adverse events in a
      cohort of children treated for MDR-TB using a community-based treatment delivery
      model. METHODS: We reviewed retrospectively the clinical charts of children <=15
      years of age treated for culture-confirmed or suspected MDR-TB between July 2007
      and January 2011. RESULTS: Nineteen children, ages two to 15, received treatment.
      At baseline, 74% of patients were co-infected with HIV, 63% were malnourished,
      84% had severe radiographic findings, and 21% had extrapulmonary disease. Five
      (26%) children had culture-confirmed MDR-TB, ten (53%) did not have culture
      results available, and four (21%) subsequently had results indicating drug
      susceptible TB. All children with HIV co-infection who were not already on
      antiretroviral therapy (ART) were initiated on ART a median of two weeks after
      the start of the MDR-TB regimen. Among the 17 patients with final outcomes, 15
      (88%) patients were cured or completed treatment, two (12%) patients died, and
      none defaulted or were lost to follow-up. The majority of patients (95%)
      experienced adverse events; only two required permanent discontinuation of the
      offending agent, and only one required suspension of MDR-TB treatment for more
      than one week. CONCLUSIONS: Pediatric MDR-TB and MDR-TB/HIV co-infection can be
      successfully treated using a combination of social support, close monitoring by
      community health workers and clinicians, and inpatient care when needed. In this
      cohort, adverse events were well tolerated and treatment outcomes were comparable
      to those reported in children with drug-susceptible TB and no HIV infection.

PMID- 22629357
TI  - Effect of streptomycin treatment on bacterial community structure in the apple
      phyllosphere.
AB  - We studied the effect of many years of streptomycin use in apple orchards on the
      proportion of phyllosphere bacteria resistant to streptomycin and bacterial
      community structure. Leaf samples were collected during early July through early
      September from four orchards that had been sprayed with streptomycin during
      spring of most years for at least 10 years and four orchards that had not been
      sprayed. The percentage of cultured phyllosphere bacteria resistant to
      streptomycin at non-sprayed orchards (mean of 65%) was greater than at sprayed
      orchards (mean of 50%) (P = 0.0271). For each orchard, a 16S rRNA gene clone
      library was constructed from leaf samples. Proteobacteria dominated the bacterial
      communities at all orchards, accounting for 71 of 104 OTUs (determined at 97%
      sequence similarity) and 93% of all sequences. The genera Massilia,
      Methylobacterium, Pantoea, Pseudomonas, and Sphingomonas were shared across all
      sites. Shannon and Simpson's diversity indices and Pielou's evenness index were
      similar among orchards regardless of streptomycin use. Analysis of Similarity
      (ANOSIM) indicated that long-term streptomycin treatment did not account for the
      observed variability in community structure among orchards (R = -0.104, P =
      0.655). Other variables, including time of summer, temperature and time at
      sampling, and relative distance of the orchards from each other, also had no
      significant effect on bacterial community structure. We conclude that factors
      other than streptomycin exposure drive both the proportion of streptomycin
      resistant bacteria and phylogenetic makeup of bacterial communities in the apple
      phyllosphere in middle to late summer.

PMID- 22629358
TI  - Wheat TaRab7 GTPase is part of the signaling pathway in responses to stripe rust
      and abiotic stimuli.
AB  - Small GTP-binding proteins function as regulators of specific intercellular
      fundamental biological processes. In this study, a small GTP-binding protein Rab7
      gene, designated as TaRab7, was identified and characterized from a cDNA library
      of wheat leaves infected with Puccinia striiformis f. sp. tritici (Pst) the wheat
      stripe rust pathogen. The gene was predicted to encode a protein of 206 amino
      acids, with a molecular mass of 23.13 KDa and an isoeletric point (pI) of 5.13.
      Further analysis revealed the presence of a conserved signature that is
      characteristic of Rab7, and phylogenetic analysis demonstrated that TaRab7 has
      the highest similarity to a small GTP binding protein gene (BdRab7-like) from
      Brachypodium distachyon. Quantitative real-time PCR assays revealed that the
      expression of TaRab7 was higher in the early stage of the incompatible
      interactions between wheat and Pst than in the compatible interaction, and the
      transcription level of TaRab7 was also highly induced by environmental stress
      stimuli. Furthermore, knocking down TaRab7 expression by virus induced gene
      silencing enhanced the susceptibility of wheat cv. Suwon 11 to an avirulent race
      CYR23. These results imply that TaRab7 plays an important role in the early stage
      of wheat-stripe rust fungus interaction and in stress tolerance.

PMID- 22629359
TI  - Circadian desynchrony promotes metabolic disruption in a mouse model of
      shiftwork.
AB  - Shiftwork is associated with adverse metabolic pathophysiology, and the rising
      incidence of shiftwork in modern societies is thought to contribute to the
      worldwide increase in obesity and metabolic syndrome. The underlying mechanisms
      are largely unknown, but may involve direct physiological effects of nocturnal
      light exposure, or indirect consequences of perturbed endogenous circadian
      clocks. This study employs a two-week paradigm in mice to model the early
      molecular and physiological effects of shiftwork. Two weeks of timed sleep
      restriction has moderate effects on diurnal activity patterns, feeding behavior,
      and clock gene regulation in the circadian pacemaker of the suprachiasmatic
      nucleus. In contrast, microarray analyses reveal global disruption of diurnal
      liver transcriptome rhythms, enriched for pathways involved in glucose and lipid
      metabolism and correlating with first indications of altered metabolism. Although
      altered food timing itself is not sufficient to provoke these effects,
      stabilizing peripheral clocks by timed food access can restore molecular rhythms
      and metabolic function under sleep restriction conditions. This study suggests
      that peripheral circadian desynchrony marks an early event in the metabolic
      disruption associated with chronic shiftwork. Thus, strengthening the peripheral
      circadian system by minimizing food intake during night shifts may counteract the
      adverse physiological consequences frequently observed in human shift workers.

PMID- 22629360
TI  - Identification of New Delhi metallo-beta-lactamase 1 in Acinetobacter lwoffii of
      food animal origin.
AB  - BACKGROUND: To investigate the presence of metallo-beta-lactamase (MBL) genes and
      the genetic environment of the New Delhi metallo-beta-lactamase gene bla(NDM-1)
      in bacteria of food animal origin. METHODOLOGY/PRINCIPAL FINDINGS: Gram-negative
      bacteria with low susceptibility to imipenem (MIC>8 ug/mL) were isolated from
      swab samples collected from 15 animal farms and one slaughterhouse in eastern
      China. These bacteria were selected for phenotypic and molecular detection of
      known MBL genes and antimicrobial susceptibility testing. For the bla(NDM-1)
      positive isolate, conjugation and transformation experiments were carried out to
      assess plasmid transfer. Southern blotting was conducted to localize the bla(NDM
      1) genes, and DNA sequencing was performed to determine the sequences of bla(NDM
      1) and the flanking genes. In total, nine gram-negative bacteria of four
      different species presented a MBL phenotype. bla(NDM-1) was identified on a
      mobile plasmid named pAL-01 in an Acinetobacter lwoffii isolate of chicken
      origin. Transfer of pAL-01 from this isolate to E. coli J53 and JM109 resulted in
      resistance to multiple beta-lactams. Sequence analysis revealed that the bla(NDM
      1) gene is attached to an intact insertion element ISAba125, whose right inverted
      repeat (IR-R) overlaps with the promoter sequence of bla(NDM-1). Thus, insertion
      of ISAba125 likely enhances the expression of bla(NDM-1). CONCLUSION: The
      identification of a bla(NDM-1)- carrying strain of A. lwoffii in chickens
      suggests the potential for zoonotic transmission of bla(NDM-1) and has important
      implications for food safety.

PMID- 22629361
TI  - Heat-induced structural changes affect OVA-antigen processing and reduce allergic
      response in mouse model of food allergy.
AB  - BACKGROUND AND AIMS: The egg protein ovalbumin (OVA) belongs to six most frequent
      food allergens. We investigated how thermal processing influences its ability to
      induce allergic symptoms and immune responses in mouse model of food allergy.
      METHODOLOGY/PRINCIPAL FINDINGS: Effect of increased temperature (70 degrees C and
      95 degrees C) on OVA secondary structure was characterized by circular dichroism
      and by the kinetics of pepsin digestion with subsequent HPLC. BALB/c mice were
      sensitized intraperitoneally and challenged with repeated gavages of OVA or OVA
      heated to 70 degrees C (h-OVA). Levels of allergen-specific serum antibodies were
      determined by ELISA (IgA and IgGs) or by beta-hexosaminidase release test (IgE).
      Specific activities of digestive enzymes were determined in brush border membrane
      vesicles of jejunal enterocytes. Cytokine production and changes in regulatory T
      cells in mesenteric lymph nodes and spleen were assessed by ELISA and FACS.
      Heating of OVA to 70 degrees C caused mild irreversible changes in secondary
      structure compared to boiling to 95 degrees C (b-OVA), but both OVA treatments
      led to markedly different digestion kinetics and Tregs induction ability in
      vitro, compared to native OVA. Heating of OVA significantly decreased clinical
      symptoms (allergic diarrhea) and immune allergic response on the level of IgE, IL
      4, IL-5, IL-13. Furthermore, h-OVA induced lower activities of serum mast cell
      protease-1 and enterocyte brush border membrane alkaline phosphatase as compared
      to native OVA. On the other hand h-OVA stimulated higher IgG2a in sera and IFN
      gamma secretion by splenocytes. CONCLUSIONS: Minor irreversible changes in OVA
      secondary structure caused by thermal processing changes both its digestion and
      antigenic epitopes formation, which leads to activation of different T cell
      subpopulations, induces shift towards Th1 response and ultimately reduces its
      allergenicity.

PMID- 22629362
TI  - Circulating zonulin, a marker of intestinal permeability, is increased in
      association with obesity-associated insulin resistance.
AB  - Zonulin is the only physiological mediator known to regulate intestinal
      permeability reversibly by modulating intercellular tight junctions. To
      investigate the relationship between intestinal permeability and obesity
      associated metabolic disturbances in humans, we aimed to study circulating
      zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA)
      was measured in 123 caucasian men in association with inflammatory and metabolic
      parameters (including minimal model-measured insulin sensitivity). Circulating
      zonulin increased with body mass index (BMI), waist to hip ratio (WHR), fasting
      insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated
      with HDL-cholesterol and insulin sensitivity. In multiple regression analysis,
      insulin sensitivity (p = 0.002) contributed independently to circulating zonulin
      variance, after controlling for the effects of BMI, fasting triglycerides and
      age. When circulating IL-6 was added to this model, only BMI (p = 0.01)
      contributed independently to circulating zonulin variance. In conclusion, the
      relationship between insulin sensitivity and circulating zonulin might be
      mediated through the obesity-related circulating IL-6 increase.

PMID- 22629363
TI  - Determinants of aortic stiffness: 16-year follow-up of the Whitehall II study.
AB  - BACKGROUND: Aortic stiffness is a strong predictor of cardiovascular disease
      endpoints. Cross-sectional studies have shown associations of various
      cardiovascular risk factors with aortic pulse wave velocity, a measure of aortic
      stiffness, but the long-term impact of these factors on aortic stiffness is
      unknown. METHODS: In 3,769 men and women from the Whitehall II cohort, a wide
      range of traditional and novel cardiovascular risk factors were determined at
      baseline (1991-1993) and aortic pulse wave velocity was measured at follow-up
      (2007-2009). The prospective associations between each baseline risk factor and
      aortic pulse wave velocity at follow-up were assessed through sex stratified
      linear regression analysis adjusted for relevant confounders. Missing data on
      baseline determinants were imputed using the Multivariate Imputation by Chained
      Equations. RESULTS: Among men, the strongest predictors were waist circumference,
      waist-hip ratio, heart rate and interleukin 1 receptor antagonist, and among
      women, adiponectin, triglycerides, pulse pressure and waist-hip ratio. The impact
      of 10 centimeter increase in waist circumference on aortic pulse wave velocity
      was twice as large for men compared with women (men: 0.40 m/s (95%-CI:
      0.24;0.56); women: 0.17 m/s (95%-CI: -0.01;0.35)), whereas the opposite was true
      for the impact of a two-fold increase in adiponectin (men: -0.30 m/s (95%-CI: 
      0.51;-0.10); women: 0.61 m/s (95%-CI: -0.86;-0.35)). CONCLUSION: In this large
      prospective study, central obesity was a strong predictor of aortic stiffness.
      Additionally, heart rate in men and adiponectin in women predicted aortic pulse
      wave velocity suggesting that strategies to prevent aortic stiffening should be
      focused differently by sex.

PMID- 22629365
TI  - Identification of postoperative prognostic microRNA predictors in hepatocellular
      carcinoma.
AB  - Comparison of microRNA (miRNA) expression profiles in the noncancerous liver
      tissues adjacent to hepatocelluar carcinomas (HCCs) was a strategy to identify
      postoperative prognostic predictors in this study. Expression profiles of 270
      miRNAs were determined in the paraneoplastic liver tissues of 12 HCC patients
      with known postoperative prognosis. A panel of candidate miRNA predictors was
      identified. The prognostic predictive value of these candidate miRNAs was then
      verified in 216 postoperative HCC patients. Univariate analysis identified 8 and
      3 miRNA predictors for recurrence-free (RFS) and overall (OS) survivals,
      respectively. Multivariate analysis revealed high expression levels of miR-155
      (HR, 2.002 [1.324-3.027]; P = .001), miR-15a (HR, 0.478 [0.248-0.920]; P = .027),
      miR-432 (HR, 1.816 [1.203-2.740]; P = .015), miR-486-3p (HR, 0.543 [0.330-0.893];
      P = .016), miR-15b (HR, 1.074 [1.002-1.152]; P = .043) and miR-30b (HR, 1.102
      [1.025-1.185]; P = .009) were significantly associated with RFS. When
      clinicopathological predictors were included, multivariate analysis revealed that
      tumor number and miR-432, miR-486-3p, and miR-30b expression levels remained
      significant as independent predictors for RFS. Additionally, expression knockdown
      of miR-155 in J7 and Mahlavu hepatoma cells resulted in decreased cell growth and
      enhanced cell death in xenograft tumors, suggesting an oncogenic effect of miR
      155. In conclusion, significant prognostic miRNA predictors were identified
      through examination of miRNA expression levels in paraneoplastic liver tissues.
      Functional analysis of a miRNA predictor, miR-155, suggested that the prognostic
      miRNA predictors identified under this strategy could serve as potential
      molecular targets for anticancer therapy.

PMID- 22629366
TI  - Left inferior frontal activations depending on the canonicity determined by the
      argument structures of ditransitive sentences: an MEG study.
AB  - To elucidate the relationships between syntactic and semantic processes, one
      interesting question is how syntactic structures are constructed by the argument
      structure of a verb, where each argument corresponds to a semantic role of each
      noun phrase (NP). Here we examined the effects of possessivity [sentences with or
      without a possessor] and canonicity [canonical or noncanonical word orders] using
      Japanese ditransitive sentences. During a syntactic decision task, the syntactic
      structure of each sentence would be constructed in an incremental manner based on
      the predicted argument structure of the ditransitive verb in a verb-final
      construction. Using magnetoencephalography, we found a significant canonicity
      effect on the current density in the left inferior frontal gyrus (IFG) at 530-550
      ms after the verb onset. This effect was selective to canonical sentences, and
      significant even when the precedent NP was physically identical. We suggest that
      the predictive effects associated with syntactic processing became larger for
      canonical sentences, where the NPs and verb were merged with a minimum structural
      distance, leading to the left IFG activations. For monotransitive and
      intransitive verbs, in which structural computation of the sentences was simpler
      than that of ditransitive sentences, we observed a significant effect selective
      to noncanonical sentences in the temporoparietal regions during 480-670 ms. This
      effect probably reflects difficulty in semantic processing of noncanonical
      sentences. These results demonstrate that the left IFG plays a predictive role in
      syntactic processing, which depends on the canonicity determined by argument
      structures, whereas other temporoparietal regions would subserve more semantic
      aspects of sentence processing.

PMID- 22629364
TI  - Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium
      falciparum activity and single oral dose cure in a murine malaria model.
AB  - Iron chelators for the treatment of malaria have proven therapeutic activity in
      vitro and in vivo in both humans and mice, but their clinical use is limited by
      the unsuitable absorption and pharmacokinetic properties of the few available
      iron chelators. FBS0701, (S)3"-(HO)-desazadesferrithiocin-polyether [DADFT-PE],
      is an oral iron chelator currently in Phase 2 human studies for the treatment of
      transfusional iron overload. The drug has very favorable absorption and
      pharmacokinetic properties allowing for once-daily use to deplete circulating
      free iron with human plasma concentrations in the high uM range. Here we show
      that FBS0701 has inhibition concentration 50% (IC(50)) of 6 uM for Plasmodium
      falciparum in contrast to the IC(50) for deferiprone and deferoxamine at 15 and
      30 uM respectively. In combination, FBS0701 interfered with artemisinin parasite
      inhibition and was additive with chloroquine or quinine parasite inhibition.
      FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson
      suppression test, a single dose of 100 mg/kg reduced day three parasitemia and
      prolonged survival, but did not cure mice. Treatment with a single oral dose of
      100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all
      the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or
      one day before resulted in the cure of some mice. Plasma exposures and other
      pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3
      mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure
      of the lethal P. yoelii model. Significantly, this effect persists after the
      chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron
      from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find
      clinically utility as monotherapy, a malarial prophylactic or, more likely, in
      combination with other antimalarials.

PMID- 22629367
TI  - The risk behaviors and mental health of detained adolescents: a controlled,
      prospective longitudinal study.
AB  - BACKGROUND: To assess the behavioral risk factors and mental health needs of
      adolescents in juvenile detention centers (JDC). METHOD: A total of 238 boys aged
      12-17 years was surveyed who had been admitted to a detention center and compared
      them with boys from the community (n = 238) matched for sex and age. We assessed
      behavioral risk factors and mental health problems by using the Youth Risk
      Behavior Survey questionnaire (YRBS) and the Youth Self-Report questionnaire
      (YSR). RESULTS: Young offenders had significantly higher YRBS scores than
      controls for drug use (odds ratio (OR) 5.16, 95% CI 2.27-7.84), sexual
      intercourse (OR, 2.51; 95% CI 1.55-2.90), irregular diet (4.78, 2.11-7.51),
      suicide attempts (1.96, 1.32-5.85), and physical fighting behavior (3.49, 1.60
      7.07), but not for tobacco use, alcohol use, and high-risk cycling. Young
      offenders at the time of admission (6.61, 2.58-15.2), at 6 months (3.12, 1.81
      10.1), and at 12 months (5.29, 1.98-13.3) reported statistically higher levels of
      total mental health problems than adolescents in a community sample. CONCLUSIONS:
      Young offenders have a high rate of mental and behavioral disorders. In the
      detention period, aggressive behavior, self-destructive/identity, and
      externalizing of problems improved while withdrawn, anxious or depressed, and
      internalizing of problems worsened.

PMID- 22629368
TI  - MDA-7/IL-24 induces Bcl-2 denitrosylation and ubiquitin-degradation involved in
      cancer cell apoptosis.
AB  - MDA-7/IL-24 was involved in the specific cancer apoptosis through suppression of
      Bcl-2 expression, which is a key apoptosis regulatory protein of the
      mitochondrial death pathway. However, the underlying mechanisms of this
      regulation are unclear. We report here that tumor-selective replicating
      adenovirus ZD55-IL-24 leads to Bcl-2 S-denitrosylation and concomitant
      ubiquitination, which take part in the 26S proteasome degradation. IL-24-siRNA
      completely blocks Bcl-2 ubiquitination via reversion of Bcl-2 S-denitrosylation
      and protects it from proteasomal degradation which confirmed the significant role
      of MDA-7/IL-24 in regulating posttranslational modification of Bcl-2 in cancer
      cells. Nitric oxide (NO) is a key regulator of protein S-nitrosylation and
      denitrosylation. The NO donor, sodium nitroprusside (SNP), down-regulates Bcl-2 S
      denitrosylation, attenuates Bcl-2 ubiquitination and subsequently counteracts MDA
      7/IL-24 induced cancer cell apoptosis, whereas NO inhibitor 2-(4-carboxyphenyl)
      4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (PTIO) shows the opposite effect. At
      the same time, these NO modulators fail to affect Bcl-2 phosphorylation,
      suggesting that NO regulates Bcl-2 stability in a phosphorylation-independent
      manner. In addition, Bcl-2 S-nitrosylation reduction induced by ZD55-IL-24 was
      attributed to both iNOS decrease and TrxR1 increase. iNOS-siRNA facilitates Bcl-2
      S-denitrosylation and ubiquitin-degradation, whereas the TrxR1 inhibitor
      auranofin prevents Bcl-2 from denitrosylation and ubiquitination, thus restrains
      the caspase signal pathway activation and subsequent cancer cell apoptosis. Taken
      together, our studies reveal that MDA-7/IL-24 induces Bcl-2 S-denitrosylation via
      regulation of iNOS and TrxR1. Moreover, denitrosylation of Bcl-2 results in its
      ubiquitination and subsequent caspase protease family activation, as a
      consequence, apoptosis susceptibility. These findings provide a novel insight
      into MDA-7/IL-24 induced growth inhibition and carcinoma apoptosis.

PMID- 22629369
TI  - Bone marrow stromal cells modulate mouse ENT1 activity and protect leukemia cells
      from cytarabine induced apoptosis.
AB  - BACKGROUND: Despite a high response rate to chemotherapy, the majority of
      patients with acute myeloid leukemia (AML) are destined to relapse due to
      residual disease in the bone marrow (BM). The tumor microenvironment is
      increasingly being recognized as a critical factor in mediating cancer cell
      survival and drug resistance. In this study, we propose to identify mechanisms
      involved in the chemoprotection conferred by the BM stroma to leukemia cells.
      METHODS: Using a leukemia mouse model and a human leukemia cell line, we studied
      the interaction of leukemia cells with the BM microenvironment. We evaluated in
      vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents
      mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry
      and western blotting. The activity of the equilibrative nucleoside transporter 1
      (ENT1), responsible for cytarabine cell incorporation, was investigated by
      measuring transport and intracellular accumulation of (3)H-adenosine. RESULTS:
      Leukemia cell mobilization from the bone marrow into peripheral blood in vivo
      using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to
      cytarabine, which translated into a prolonged survival advantage in our mouse
      leukemia model. In vitro, the BM stromal cells secreted a soluble factor that
      mediated significant chemoprotection to leukemia cells from cytarabine induced
      apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction
      of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine.
      No protection was observed when radiation or other cytotoxic agents such as
      etoposide, cisplatin and 5-fluorouracil were used. CONCLUSION: The BM stroma
      secretes a soluble factor that significantly protects leukemia cells from
      cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the
      chemo-protective effects mediated by the BM microenvironment may enhance the
      benefit of conventional chemotherapy for patients with AML.

PMID- 22629370
TI  - Spatial variation in foraging behaviour of a marine top predator (Phoca vitulina)
      determined by a large-scale satellite tagging program.
AB  - The harbour seal (Phoca vitulina) is a widespread marine predator in Northern
      Hemisphere waters. British populations have been subject to rapid declines in
      recent years. Food supply or inter-specific competition may be implicated but
      basic ecological data are lacking and there are few studies of harbour seal
      foraging distribution and habits. In this study, satellite tagging conducted at
      the major seal haul outs around the British Isles showed both that seal movements
      were highly variable among individuals and that foraging strategy appears to be
      specialized within particular regions. We investigated whether these apparent
      differences could be explained by individual level factors: by modelling measures
      of trip duration and distance travelled as a function of size, sex and body
      condition. However, these were not found to be good predictors of foraging trip
      duration or distance, which instead was best predicted by tagging region, time of
      year and inter-trip duration. Therefore, we propose that local habitat conditions
      and the constraints they impose are the major determinants of foraging movements.
      Specifically the distance to profitable feeding grounds from suitable haul-out
      locations may dictate foraging strategy and behaviour. Accounting for proximity
      to productive foraging resources is likely to be an important component of
      understanding population processes. Despite more extensive offshore movements
      than expected, there was also marked fidelity to the local haul-out region with
      limited connectivity between study regions. These empirical observations of
      regional exchange at short time scales demonstrates the value of large scale
      electronic tagging programs for robust characterization of at-sea foraging
      behaviour at a wide spatial scale.

PMID- 22629371
TI  - Heterologous expression of ATG8c from soybean confers tolerance to nitrogen
      deficiency and increases yield in Arabidopsis.
AB  - Nitrogen is an essential element for plant growth and yield. Improving Nitrogen
      Use Efficiency (NUE) of crops could potentially reduce the application of
      chemical fertilizer and alleviate environmental damage. To identify new NUE genes
      is therefore an important task in molecular breeding. Macroautophagy (autophagy)
      is an intracellular process in which damaged or obsolete cytoplasmic components
      are encapsulated in double membraned vesicles termed autophagosomes, then
      delivered to the vacuole for degradation and nutrient recycling. One of the core
      components of autophagosome formation, ATG8, has been shown to directly mediate
      autophagosome expansion, and the transcript of which is highly inducible upon
      starvation. Therefore, we postulated that certain homologs of Saccharomyces
      cerevisiae ATG8 (ScATG8) from crop species could have potential for NUE crop
      breeding. A soybean (Glycine max, cv. Zhonghuang-13) ATG8, GmATG8c, was selected
      from the 11 family members based on transcript analysis upon nitrogen
      deprivation. GmATG8c could partially complement the yeast atg8 mutant.
      Constitutive expression of GmATG8c in soybean callus cells not only enhanced
      nitrogen starvation tolerance of the cells but accelerated the growth of the
      calli. Transgenic Arabidopsis over-expressing GmATG8c performed better under
      extended nitrogen and carbon starvation conditions. Meanwhile, under optimum
      growth conditions, the transgenic plants grew faster, bolted earlier, produced
      larger primary and axillary inflorescences, eventually produced more seeds than
      the wild-type. In average, the yield was improved by 12.9%. We conclude that
      GmATG8c may serve as an excellent candidate for breeding crops with enhanced NUE
      and better yield.

PMID- 22629372
TI  - Conserved Orb6 phosphorylation sites are essential for polarized cell growth in
      Schizosaccharomyces pombe.
AB  - The Ndr-related Orb6 kinase is a key regulator of polarized cell growth in
      fission yeast, however the mechanism of Orb6 activation is unclear. Activation of
      other Ndr kinases involves both autophosphorylation and phosphorylation by an
      upstream kinase. Previous reports suggest that the Nak1 kinase functions upstream
      from Orb6. Supporting this model, we show that HA-Orb6 overexpression partially
      restored cell polarity in nak1 ts cells. We also demonstrated by
      coimmunoprecipitation and in vitro binding assays that Nak1 and Orb6 physically
      interact, and that the Nak1 C-terminal region is required for Nak1/Orb6 complex
      formation in vivo. However, results from in vitro kinase assays did not show
      phosphorylation of recombinant Orb6 by HA-Nak1, suggesting that Orb6 activation
      may not involve direct phosphorylation by Nak1. To investigate the role of Orb6
      phosphorylation and activity, we substituted Ala at the ATP-binding and conserved
      phosphorylation sites. Overexpression of kinase-dead HA-Orb6(K122A) in wild-type
      cells resulted in a loss of cell polarity, suggesting that it has a dominant
      negative effect, and it failed to rescue the polarity defect of nak1 or orb6 ts
      mutants. Recombinant GST-Orb6(S291A) did not autophosphorylate in vitro
      suggesting that Ser291 is the primary autophosphorylation site. HA-Orb6(S291A)
      overexpression only partially rescued the orb6 polarity defect and failed to
      rescue the nak1 defect, suggesting that autophosphorylation is important for Orb6
      function. GST-Orb6(T456A) autophosphorylated in vitro, indicating that the
      conserved phosphorylation site at Thr456 is not essential for kinase activity.
      However, HA-Orb6(T456A) overexpression had similar effects as overexpressing
      kinase-dead HA-Orb6(K122A), suggesting that Thr456 is essential for Orb6 function
      in vivo. Also, we found that both phosphorylation site mutations impaired the
      ability of Myc-Nak1 to coimmunoprecipitate with HA-Orb6. Together, our results
      suggest a model whereby autophosphorylation of Ser291 and phosphorylation of
      Thr456 by an upstream kinase promote Nak1/Orb6 complex formation and Orb6
      activation.

PMID- 22629374
TI  - Insect pollinated crops, insect pollinators and US agriculture: trend analysis of
      aggregate data for the period 1992-2009.
AB  - In the US, the cultivated area (hectares) and production (tonnes) of crops that
      require or benefit from insect pollination (directly dependent crops: apples,
      almonds, blueberries, cucurbits, etc.) increased from 1992, the first year in
      this study, through 1999 and continued near those levels through 2009; aggregate
      yield (tonnes/hectare) remained unchanged. The value of directly dependent crops
      attributed to all insect pollination (2009 USD) decreased from $14.29 billion in
      1996, the first year for value data in this study, to $10.69 billion in 2001, but
      increased thereafter, reaching $15.12 billion by 2009. The values attributed to
      honey bees and non-Apis pollinators followed similar patterns, reaching $11.68
      billion and $3.44 billion, respectively, by 2009. The cultivated area of crops
      grown from seeds resulting from insect pollination (indirectly dependent crops:
      legume hays, carrots, onions, etc.) was stable from 1992 through 1999, but has
      since declined. Production of those crops also declined, albeit not as rapidly as
      the decline in cultivated area; this asymmetry was due to increases in aggregate
      yield. The value of indirectly dependent crops attributed to insect pollination
      declined from $15.45 billion in 1996 to $12.00 billion in 2004, but has since
      trended upward. The value of indirectly dependent crops attributed to honey bees
      and non-Apis pollinators, exclusive of alfalfa leafcutter bees, has declined
      since 1996 to $5.39 billion and $1.15 billion, respectively in 2009. The value of
      alfalfa hay attributed to alfalfa leafcutter bees ranged between $4.99 and $7.04
      billion. Trend analysis demonstrates that US producers have a continued and
      significant need for insect pollinators and that a diminution in managed or wild
      pollinator populations could seriously threaten the continued production of
      insect pollinated crops and crops grown from seeds resulting from insect
      pollination.

PMID- 22629376
TI  - A new Chanidae (Ostariophysii: Gonorynchiformes) from the Cretaceous of Brazil
      with affinities to Laurasian gonorynchiforms from Spain.
AB  - Based on specimens originally referred to as "Dastilbe minor", a nomem-nudum, we
      describe a new genus of Chanidae ?Nanaichthys longipinnus nov. gen. and sp. which
      exhibits several diagnostic characters such as the absence of orbitosphenoid and
      basisphenoid, anteriorly displaced quadrate-mandibular articulation, laterally
      expanded supraneurals, an acute angle between the preopercular limbs, expansion
      at the angle between the preopercular limbs, and a curved maxillary articular
      process. Its occurrence and supposed relationship within the Chanidae reinforce
      the influence of the Mediterranean Tethys over the Gondwanan main rift system
      prior to the Aptian/Albian highstands.

PMID- 22629375
TI  - Reduction in inter-hemispheric connectivity in disorders of consciousness.
AB  - Clinical diagnosis of disorders of consciousness (DOC) caused by brain injury
      poses great challenges since patients are often behaviorally unresponsive. A
      promising new approach towards objective DOC diagnosis may be offered by the
      analysis of ultra-slow (<0.1 Hz) spontaneous brain activity fluctuations measured
      with functional magnetic resonance imaging (fMRI) during the resting-state.
      Previous work has shown reduced functional connectivity within the "default
      network", a subset of regions known to be deactivated during engaging tasks,
      which correlated with the degree of consciousness impairment. However, it remains
      unclear whether the breakdown of connectivity is restricted to the "default
      network", and to what degree changes in functional connectivity can be observed
      at the single subject level. Here, we analyzed resting-state inter-hemispheric
      connectivity in three homotopic regions of interest, which could reliably be
      identified based on distinct anatomical landmarks, and were part of the
      "Extrinsic" (externally oriented, task positive) network (pre- and postcentral
      gyrus, and intraparietal sulcus). Resting-state fMRI data were acquired for a
      group of 11 healthy subjects and 8 DOC patients. At the group level, our results
      indicate decreased inter-hemispheric functional connectivity in subjects with
      impaired awareness as compared to subjects with intact awareness. Individual
      connectivity scores significantly correlated with the degree of consciousness.
      Furthermore, a single-case statistic indicated a significant deviation from the
      healthy sample in 5/8 patients. Importantly, of the three patients whose
      connectivity indices were comparable to the healthy sample, one was diagnosed as
      locked-in. Taken together, our results further highlight the clinical potential
      of resting-state connectivity analysis and might guide the way towards a
      connectivity measure complementing existing DOC diagnosis.

PMID- 22629377
TI  - Multitrophic interaction in the rhizosphere of maize: root feeding of Western
      corn rootworm larvae alters the microbial community composition.
AB  - BACKGROUND: Larvae of the Western Corn Rootworm (WCR) feeding on maize roots
      cause heavy economical losses in the US and in Europe. New or adapted pest
      management strategies urgently require a better understanding of the multitrophic
      interaction in the rhizosphere. This study aimed to investigate the effect of WCR
      root feeding on the microbial communities colonizing the maize rhizosphere.
      METHODOLOGY/PRINCIPAL FINDINGS: In a greenhouse experiment, maize lines KWS13,
      KWS14, KWS15 and MON88017 were grown in three different soil types in presence
      and in absence of WCR larvae. Bacterial and fungal community structures were
      analyzed by denaturing gradient gel electrophoresis (DGGE) of the 16S rRNA gene
      and ITS fragments, PCR amplified from the total rhizosphere community DNA. DGGE
      bands with increased intensity were excised from the gel, cloned and sequenced in
      order to identify specific bacteria responding to WCR larval feeding. DGGE
      fingerprints showed that the soil type and the maize line influenced the fungal
      and bacterial communities inhabiting the maize rhizosphere. WCR larval feeding
      affected the rhiyosphere microbial populations in a soil type and maize line
      dependent manner. DGGE band sequencing revealed an increased abundance of
      Acinetobacter calcoaceticus in the rhizosphere of several maize lines in all soil
      types upon WCR larval feeding. CONCLUSION/SIGNIFICANCE: The effects of both
      rhizosphere and WCR larval feeding seemed to be stronger on bacterial communities
      than on fungi. Bacterial and fungal community shifts in response to larval
      feeding were most likely due to changes of root exudation patterns. The increased
      abundance of A. calcoaceticus suggested that phenolic compounds were released
      upon WCR wounding.

PMID- 22629378
TI  - The expression of small regulatory RNAs in clinical samples reflects the
      different life styles of Staphylococcus aureus in colonization vs. infection.
AB  - Small RNAs (sRNAs) are involved in the post-transcriptional regulation of
      metabolic pathways and in responses to stress and virulence. We analyzed the
      expression levels of five sRNAs of Staphylococcus aureus during human
      colonization or infection. Total RNA was isolated from nasal carriers, abscesses
      and cystic fibrosis patients (20 subjects per condition). The expression levels
      of the sRNAs were measured in the clinical samples and compared with those of the
      corresponding strains grown in vitro. Five sRNAs were encoded and expressed in
      all clinical strains in vitro. In vivo, the global expression of the five sRNAs
      was extremely variable in the abscessed patients, more homogeneous in the cystic
      fibrosis patients, and highly uniform in the nasal carrier samples. The
      expression levels of the sRNAs in vivo resembled those obtained at exponential
      phase or late exponential phase of growth in vitro, for three and one sRNA
      respectively; while for one sRNA, the expression was always higher in vivo as
      compared to in vitro growth. The in vitro conditions do not uniformly mimic the
      in vivo conditions for sRNA expression. Nasal colonization is associated with a
      unique expression pattern of sRNA that might reflect the commensalism of S.
      aureus in this niche.

PMID- 22629373
TI  - Genome and transcriptome analysis of the food-yeast Candida utilis.
AB  - The industrially important food-yeast Candida utilis is a Crabtree effect
      negative yeast used to produce valuable chemicals and recombinant proteins. In
      the present study, we conducted whole genome sequencing and phylogenetic analysis
      of C. utilis, which showed that this yeast diverged long before the formation of
      the CUG and Saccharomyces/Kluyveromyces clades. In addition, we performed
      comparative genome and transcriptome analyses using next-generation sequencing,
      which resulted in the identification of genes important for characteristic
      phenotypes of C. utilis such as those involved in nitrate assimilation, in
      addition to the gene encoding the functional hexose transporter. We also found
      that an antisense transcript of the alcohol dehydrogenase gene, which in silico
      analysis did not predict to be a functional gene, was transcribed in the
      stationary-phase, suggesting a novel system of repression of ethanol production.
      These findings should facilitate the development of more sophisticated systems
      for the production of useful reagents using C. utilis.

PMID- 22629379
TI  - A quantitative 3D motility analysis of Trypanosoma brucei by use of digital in
      line holographic microscopy.
AB  - We present a quantitative 3D analysis of the motility of the blood parasite
      Trypanosoma brucei. Digital in-line holographic microscopy has been used to track
      single cells with high temporal and spatial accuracy to obtain quantitative data
      on their behavior. Comparing bloodstream form and insect form trypanosomes as
      well as mutant and wildtype cells under varying external conditions we were able
      to derive a general two-state-run-and-tumble-model for trypanosome motility.
      Differences in the motility of distinct strains indicate that adaption of the
      trypanosomes to their natural environments involves a change in their mode of
      swimming.

PMID- 22629380
TI  - Human U87 astrocytoma cell invasion induced by interaction of betaig-h3 with
      integrin alpha5beta1 involves calpain-2.
AB  - It is known that betaig-h3 is involved in the invasive process of many types of
      tumors, but its mechanism in glioma cells has not been fully clarified. Using
      immunofluorescent double-staining and confocal imaging analysis, and co
      immunoprecipitation assays, we found that betaig-h3 co-localized with integrin
      alpha5beta1 in U87 cells. We sought to elucidate the function of this interaction
      by performing cell invasion assays and gelatin zymography experiments. We found
      that siRNA knockdowns of betaig-h3 and calpain-2 impaired cell invasion and MMP
      secretion. Moreover, betaig-h3, integrins and calpain-2 are known to be regulated
      by Ca(2+), and they are also involved in tumor cell invasion. Therefore, we
      further investigated if calpain-2 was relevant to betaig-h3-integrin alpha5beta1
      interaction to affect U87 cell invasion. Our data showed that betaig-h3 co
      localized with integrin alpha5beta1 to enhance the invasion of U87 cells, and
      that calpain-2, is involved in this process, acting as a downstream molecule.

PMID- 22629381
TI  - A molecular diagnostic tool to replace larval culture in conventional faecal egg
      count reduction testing in sheep.
AB  - The accurate diagnosis of parasitic nematode infections in livestock (including
      sheep and goats) is central to their effective control and the detection of the
      anthelmintic resistance. Traditionally, the faecal egg count reduction test
      (FECRT), combined with the technique of larval culture (LC), has been used widely
      to assess drug-susceptibility/resistance in strongylid nematodes. However, this
      approach suffers from a lack of specificity, sensitivity and reliability, and is
      time-consuming and costly to conduct. Here, we critically assessed a specific PCR
      assay to support FECRT, in a well-controlled experiment on sheep with naturally
      acquired strongylid infections known to be resistant to benzimidazoles. We showed
      that the PCR results were in close agreement with those of total worm count
      (TWC), but not of LC. Importantly, albendazole resistance detected by PCR-coupled
      FECRT was unequivocally linked to Teladorsagia circumcincta and, to lesser
      extent, Trichostrongylus colubriformis, a result that was not achievable by LC.
      The key findings from this study demonstrate that our PCR-coupled FECRT approach
      has major merit for supporting anthelmintic resistance in nematode populations.
      The findings also show clearly that our PCR assay can be used as an alternative
      to LC, and is more time-efficient and less laborious, which has important
      practical implications for the effective management and control strongylid
      nematodes of sheep.

PMID- 22629382
TI  - Lack of PPARgamma in myeloid cells confers resistance to Listeria monocytogenes
      infection.
AB  - The peroxisomal proliferator-activated receptor gamma (PPARgamma) is a nuclear
      receptor that controls inflammation and immunity. Innate immune defense against
      bacterial infection appears to be compromised by PPARgamma. The relevance of
      PPARgamma in myeloid cells, that organize anti-bacterial immunity, for the
      outcome of immune responses against intracellular bacteria such as Listeria
      monocytogenes in vivo is unknown. We found that Listeria monocytogenes infection
      of macrophages rapidly led to increased expression of PPARgamma. This prompted us
      to investigate whether PPARgamma in myeloid cells influences innate immunity
      against Listeria monocytogenes infection by using transgenic mice with myeloid
      cell specific ablation of PPARgamma (LysMCre*PPARgamma(flox/flox)). Loss of
      PPARgamma in myeloid cells results in enhanced innate immune defense against
      Listeria monocytogenes infection both, in vitro and in vivo. This increased
      resistance against infection was characterized by augmented levels of
      bactericidal factors and inflammatory cytokines: ROS, NO, IFNgamma TNF IL-6 and
      IL-12. Moreover, myeloid cell-specific loss of PPARgamma enhanced chemokine and
      adhesion molecule expression leading to improved recruitment of inflammatory
      Ly6C(hi) monocytes to sites of infection. Importantly, increased resistance
      against Listeria infection in the absence of PPARgamma was not accompanied by
      enhanced immunopathology. Our results elucidate a yet unknown regulatory network
      in myeloid cells that is governed by PPARgamma and restrains both listeriocidal
      activity and recruitment of inflammatory monocytes during Listeria infection,
      which may contribute to bacterial immune escape. Pharmacological interference
      with PPARgamma activity in myeloid cells might represent a novel strategy to
      overcome intracellular bacterial infection.

PMID- 22629384
TI  - Species-area relationships are controlled by species traits.
AB  - The species-area relationship (SAR) is one of the most thoroughly investigated
      empirical relationships in ecology. Two theories have been proposed to explain
      SARs: classical island biogeography theory and niche theory. Classical island
      biogeography theory considers the processes of persistence, extinction, and
      colonization, whereas niche theory focuses on species requirements, such as
      habitat and resource use. Recent studies have called for the unification of these
      two theories to better explain the underlying mechanisms that generates SARs. In
      this context, species traits that can be related to each theory seem promising.
      Here we analyzed the SARs of butterfly and moth assemblages on islands differing
      in size and isolation. We tested whether species traits modify the SAR and the
      response to isolation. In addition to the expected overall effects on the area,
      traits related to each of the two theories increased the model fit, from 69% up
      to 90%. Steeper slopes have been shown to have a particularly higher sensitivity
      to area, which was indicated by species with restricted range (slope = 0.82),
      narrow dietary niche (slope= 0.59), low abundance (slope= 0.52), and low
      reproductive potential (slope = 0.51). We concluded that considering species
      traits by analyzing SARs yields considerable potential for unifying island
      biogeography theory and niche theory, and that the systematic and predictable
      effects observed when considering traits can help to guide conservation and
      management actions.

PMID- 22629383
TI  - Soluble and cell-associated insulin receptor dysfunction correlates with severity
      of HAND in HIV-infected women.
AB  - BACKGROUND: Blood sugar metabolism abnormalities have been identified in HIV
      infected individuals and associated with HIV-associated neurocognitive disorders
      (HAND). These abnormalities may occur as a result of chronic HIV infection, long
      term use of combined antiretroviral treatment (CART), aging, genetic
      predisposition, or a combination of these factors, and may increase morbidity and
      mortality in this population. OBJECTIVE: To determine if changes in soluble and
      cell-associated insulin receptor (IR) levels, IR substrate-1 (IRS-1) levels, and
      IRS-1 tyrosine phosphorylation are associated with the presence and severity of
      HAND in a cohort of HIV-seropositive women. METHODS AND RESULTS: This is a
      retrospective cross-sectional study using patient database information and stored
      samples from 34 HIV-seropositive women and 10 controls without history of
      diabetes from the Hispanic-Latino Longitudinal Cohort of Women. Soluble IR
      subunits [sIR, ectodomain (alpha) and full-length or intact (alphabeta)] were
      assayed in plasma and CSF samples by ELISA. Membrane IR levels, IRS-1 levels, and
      IRS-1 tyrosine phosphorylation were analyzed in CSF white cell pellets (WCP)
      using flow cytometry. HIV-seropositive women had significantly increased levels
      of intact or full-length sIR in plasma (p<0.001) and CSF (p<0.005) relative to
      controls. Stratified by HAND, increased levels of full-length sIR in plasma were
      associated with the presence (p<0.001) and severity (p<0.005) of HAND. A
      significant decrease in IRS-1 tyrosine-phosphorylation in the WCP was also
      associated with the presence (p<0.02) and severity (p<0.02) of HAND. CONCLUSIONS:
      This study provides evidence that IR secretion is increased in HIV-seropositive
      women, and increased IR secretion is associated with cognitive impairment in
      these women. Thus, IR dysfunction may have a role in the progression of HAND and
      could represent a biomarker for the presence and severity of HAND.

PMID- 22629385
TI  - Identification of microRNAs inhibiting TGF-beta-induced IL-11 production in bone
      metastatic breast cancer cells.
AB  - Development of bone metastases is dependent on the cancer cell-bone cell
      interactions in the bone microenvironment. Transforming growth factor beta (TGF
      beta) is released from bone during osteoclastic bone resorption and induces
      production of osteolytic factors, such as interleukin 11 (IL-11), in breast
      cancer cells. IL-11 in turn increases osteolysis by stimulating osteoclast
      function, launching a vicious cycle of cancer growth and bone destruction. We
      aimed to identify and functionally characterize microRNAs (miRNAs) that mediate
      the bone metastatic process, focusing on miRNAs that regulate the TGF-beta
      induction of IL-11. First, we profiled the expression of 455 miRNAs in a highly
      bone metastatic MDA-MB-231(SA) variant as compared to the parental MDA-MB-231
      breast cancer cell line and found 16 miRNAs (3.5%) having a >3-fold expression
      difference between the two cell types. We then applied a cell-based
      overexpression screen with Pre-miRNA constructs to functionally identify miRNAs
      regulating TGF-beta-induced IL-11 production. This analysis pinpointed miR-204,
      miR-211, and miR-379 as such key regulators. These miRNAs were shown to directly
      target IL11 by binding to its 3' UTR. MiR-379 also inhibited Smad2/3/4-mediated
      transcriptional activity. Gene expression analysis of miR-204 and miR-379
      transfected cells indicated that these miRNAs downregulated the expression of
      several genes involved in TGF-beta signaling, including prostaglandin
      endoperoxide synthase 2 (PTGS2). In addition, there was a significant correlation
      between the genes downregulated by miR-379 and a set of genes upregulated in
      basal subtype of breast cancer. Taken together, the functional evidence and
      clinical correlations imply novel mechanistic links between miRNAs and the key
      steps in the bone metastatic process in breast cancer, with potential clinical
      relevance.

PMID- 22629386
TI  - Interaction of Rio1 kinase with toyocamycin reveals a conformational switch that
      controls oligomeric state and catalytic activity.
AB  - Rio1 kinase is an essential ribosome-processing factor required for proper
      maturation of 40 S ribosomal subunit. Although its structure is known, several
      questions regarding its functional remain to be addressed. We report that both
      Archaeoglobus fulgidus and human Rio1 bind more tightly to an adenosine analog,
      toyocamycin, than to ATP. Toyocamycin has antibiotic, antiviral and cytotoxic
      properties, and is known to inhibit ribosome biogenesis, specifically the
      maturation of 40 S. We determined the X-ray crystal structure of toyocamycin
      bound to Rio1 at 2.0 A and demonstrated that toyocamycin binds in the ATP binding
      pocket of the protein. Despite this, measured steady state kinetics were
      inconsistent with strict competitive inhibition by toyocamycin. In analyzing this
      interaction, we discovered that Rio1 is capable of accessing multiple distinct
      oligomeric states and that toyocamycin may inhibit Rio1 by stabilizing a less
      catalytically active oligomer. We also present evidence of substrate inhibition
      by high concentrations of ATP for both archaeal and human Rio1. Oligomeric state
      studies show both proteins access a higher order oligomeric state in the presence
      of ATP. The study revealed that autophosphorylation by Rio1 reduces oligomer
      formation and promotes monomerization, resulting in the most active species.
      Taken together, these results suggest the activity of Rio1 may be modulated by
      regulating its oligomerization properties in a conserved mechanism, identifies
      the first ribosome processing target of toyocamycin and presents the first small
      molecule inhibitor of Rio1 kinase activity.

PMID- 22629387
TI  - Out of sight but not out of mind: alternative means of communication in plants.
AB  - Current knowledge suggests that the mechanisms by which plants communicate
      information take numerous forms. Previous studies have focussed their attention
      on communication via chemicals, contact and light; other methods of interaction
      between plants have remained speculative. In this study we tested the ability of
      young chilli plants to sense their neighbours and identify their relatives using
      alternative mechanism(s) to recognised plant communication pathways. We found
      that the presence of a neighbouring plant had a significant influence on seed
      germination even when all known sources of communication signals were blocked.
      Furthermore, despite the signalling restriction, seedlings allocated energy to
      their stem and root systems differently depending on the identity of the
      neighbour. These results provide clear experimental evidence for the existence of
      communication channels between plants beyond those that have been recognized and
      studied thus far.

PMID- 22629388
TI  - Effect of iron overload and iron deficiency on liver hemojuvelin protein.
AB  - INTRODUCTION: Hemojuvelin (Hjv) is a key component of the signaling cascade that
      regulates liver hepcidin (Hamp) expression. The purpose of this study was to
      determine Hjv protein levels in mice and rats subjected to iron overload and iron
      deficiency. METHODS: C57BL/6 mice were injected with iron (200 mg/kg); iron
      deficiency was induced by feeding of an iron-deficient diet, or by repeated
      phlebotomies. Erythropoietin (EPO)-treated mice were administered recombinant EPO
      at 50 U/mouse. Wistar rats were injected with iron (1200 mg/kg), or fed an iron
      deficient diet. Hjv protein was determined by immunoblotting, liver samples from
      Hjv-/- mice were used as negative controls. Mouse plasma Hjv content was
      determined by a commercial ELISA kit. RESULTS: Liver crude membrane fraction from
      both mice and rats displayed a major Hjv-specific band at 35 kDa, and a weaker
      band of 20 kDa. In mice, the intensity of these bands was not changed following
      iron injection, repeated bleeding, low iron diet or EPO administration. No change
      in liver crude membrane Hjv protein was observed in iron-treated or iron
      deficient rats. ELISA assay for mouse plasma Hjv did not show significant
      difference between Hjv+/+ and Hjv-/- mice. Liver Hamp mRNA, Bmp6 mRNA and Id1
      mRNA displayed the expected response to iron overload and iron deficiency. EPO
      treatment decreased Id1 mRNA, suggesting possible participation of the bone
      morphogenetic protein pathway in EPO-mediated downregulation of Hamp mRNA.
      DISCUSSION: Since no differences between Hjv protein levels were found following
      various experimental manipulations of body iron status, the results indicate
      that, in vivo, substantial changes in Hamp mRNA can occur without noticeable
      changes of membrane hemojuvelin content. Therefore, modulation of hemojuvelin
      protein content apparently does not represent the limiting step in the control of
      Hamp gene expression.

PMID- 22629389
TI  - HeT-A_pi1, a piRNA target sequence in the Drosophila telomeric retrotransposon
      HeT-A, is extremely conserved across copies and species.
AB  - The maintenance of the telomeres in Drosophila species depends on the
      transposition of the non-LTR retrotransposons HeT-A, TAHRE and TART. HeT-A and
      TART elements have been found in all studied species of Drosophila suggesting
      that their function has been maintained for more than 60 million years. Of the
      three elements, HeT-A is by far the main component of D. melanogaster telomeres
      and, unexpectedly for an element with an essential role in telomere elongation,
      the conservation of the nucleotide sequence of HeT-A is very low. In order to
      better understand the function of this telomeric retrotransposon, we studied the
      degree of conservation along HeT-A copies. We identified a small sequence within
      the 3' UTR of the element that is extremely conserved among copies of the element
      both, within D. melanogaster and related species from the melanogaster group. The
      sequence corresponds to a piRNA target in D. melanogaster that we named HeT
      A_pi1. Comparison with piRNA target sequences from other Drosophila
      retrotransposons showed that HeT-A_pi1 is the piRNA target in the Drosophila
      genome with the highest degree of conservation among species from the
      melanogaster group. The high conservation of this piRNA target in contrast with
      the surrounding sequence, suggests an important function of the HeT-A_pi1
      sequence in the co-evolution of the HeT-A retrotransposon and the Drosophila
      genome.

PMID- 22629390
TI  - Traffic-related air pollution and DNA damage: a longitudinal study in Taiwanese
      traffic conductors.
AB  - BACKGROUND: There is accumulating epidemiologic evidence that exposure to traffic
      related air pollutants, including particulate matter (PM) and polyaromatic hydro
      carbons (PAHs), plays a role in etiology and prognosis of a large scale of
      illnesses, although the role of specific causal agents and underlying mechanisms
      for different health outcomes remains unknown. OBJECTIVE: Our general objective
      was to assess the relations between personal exposure to traffic exhausts, in
      particular ambient PM(2.5) and PAHs, and the occurrence of DNA strand breaks by
      applying personal monitoring of PM and biomarkers of exposure (urinary 1
      hydroxypyrene-glucuronide, 1-OHPG) and effect (urinary 8-hydroxydeoxyguanosine, 8
      OHdG and DNA strand breaks). METHODS: We recruited 91 traffic conductors and 53
      indoor office workers between May 2009 and June 2011 in Taipei City, Taiwan. We
      used PM(2.5) personal samplers to collect breathing-zone particulate PAHs
      samples. Spot urine and blood samples after work shift of 2 consecutive days were
      analyzed for 1-OHPG, 8-OHdG and DNA strand breaks, respectively. Statistical
      methods included linear regression and mixed models. RESULTS: Urinary 8-OHdG
      levels and the occurrence of DNA strand breaks in traffic conductors
      significantly exceeded those in indoor office workers in mixed models.
      Particulate PAHs levels showed a positive association with urinary 1-OHPG in the
      regression model (beta = 0.056, p = 0.01). Urinary 1-OHPG levels were
      significantly associated with urinary 8-OHdG levels in the mixed model (beta =
      0.101, p = 0.023). Our results provide evidence that exposure to fine
      particulates causes DNA damage. Further, particulate PAHs could be biologically
      active constituents of PM(2.5) with reference to the induction of oxidative DNA
      damages.

PMID- 22629391
TI  - Conflict of interest policies for organizations producing a large number of
      clinical practice guidelines.
AB  - BACKGROUND: Conflict of interest (COI) of clinical practice guideline (CPG)
      sponsors and authors is an important potential source of bias in CPG development.
      The objectives of this study were to describe the COI policies for organizations
      currently producing a significant number of CPGs, and to determine if these
      policies meet 2011 Institute of Medicine (IOM) standards. METHODOLOGY/PRINCIPAL
      FINDINGS: We identified organizations with five or more guidelines listed in the
      National Guideline Clearinghouse between January 1, 2009 and November 5, 2010. We
      obtained the COI policy for each organization from publicly accessible sources,
      most often the organization's website, and compared those polices to IOM
      standards related to COI. 37 organizations fulfilled our inclusion criteria, of
      which 17 (46%) had a COI policy directly related to CPGs. These COI policies
      varied widely with respect to types of COI addressed, from whom disclosures were
      collected, monetary thresholds for disclosure, approaches to management, and
      updating requirements. Not one organization's policy adhered to all seven of the
      IOM standards that were examined, and nine organizations did not meet a single
      one of the standards. CONCLUSIONS/SIGNIFICANCE: COI policies among organizations
      producing a large number of CPGs currently do not measure up to IOM standards
      related to COI disclosure and management. CPG developers need to make significant
      improvements in these policies and their implementation in order to optimize the
      quality and credibility of their guidelines.

PMID- 22629392
TI  - Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates Akt
      signaling.
AB  - O-linked N-acetylglucosamine glycosylations (O-GlcNAc) and O-linked
      phosphorylations (O-phosphate), as two important types of post-translational
      modifications, often occur on the same protein and bear a reciprocal
      relationship. In addition to the well documented phosphorylations that control
      Akt activity, Akt also undergoes O-GlcNAcylation, but the interplay between these
      two modifications and the biological significance remain unclear, largely due to
      the technique challenges. Here, we applied a two-step analytic approach composed
      of the O-GlcNAc immunoenrichment and subsequent O-phosphate immunodetection. Such
      an easy method enabled us to visualize endogenous glycosylated and phosphorylated
      Akt subpopulations in parallel and observed the inhibitory effect of Akt O
      GlcNAcylations on its phosphorylation. Further studies utilizing mass
      spectrometry and mutagenesis approaches showed that O-GlcNAcylations at Thr 305
      and Thr 312 inhibited Akt phosphorylation at Thr 308 via disrupting the
      interaction between Akt and PDK1. The impaired Akt activation in turn resulted in
      the compromised biological functions of Akt, as evidenced by suppressed cell
      proliferation and migration capabilities. Together, this study revealed an
      extensive crosstalk between O-GlcNAcylations and phosphorylations of Akt and
      demonstrated O-GlcNAcylation as a new regulatory modification for Akt signaling.

PMID- 22629393
TI  - Dual infection and superinfection inhibition of epithelial skin cells by two
      alphaherpesviruses co-occur in the natural host.
AB  - Hosts can be infected with multiple herpesviruses, known as superinfection;
      however, superinfection of cells is rare due to the phenomenon known as
      superinfection inhibition. It is believed that dual infection of cells occurs in
      nature, based on studies examining genetic exchange between homologous
      alphaherpesviruses in the host, but to date, this has not been directly shown in
      a natural model. In this report, gallid herpesvirus 2 (GaHV-2), better known as
      Marek's disease virus (MDV), was used in its natural host, the chicken, to
      determine whether two homologous alphaherpesviruses can infect the same cells in
      vivo. MDV shares close similarities with the human alphaherpesvirus, varicella
      zoster virus (VZV), with respect to replication in the skin and exit from the
      host. Recombinant MDVs were generated that express either the enhanced GFP (eGFP)
      or monomeric RFP (mRFP) fused to the UL47 (VP13/14) herpesvirus tegument protein.
      These viruses exhibited no alteration in pathogenic potential and expressed
      abundant UL47-eGFP or -mRFP in feather follicle epithelial cells in vivo. Using
      laser scanning confocal microscopy, it was evident that these two similar, but
      distinguishable, viruses were able to replicate within the same cells of their
      natural host. Evidence of superinfection inhibition was also observed. These
      results have important implications for two reasons. First, these results show
      that during natural infection, both dual infection of cells and superinfection
      inhibition can co-occur at the cellular level. Secondly, vaccination against MDV
      with homologous alphaherpesvirus like attenuated GaHV-2, or non-oncogenic GaHV-3
      or meleagrid herpesvirus (MeHV-1) has driven the virus to greater virulence and
      these results implicate the potential for genetic exchange between homologous
      avian alphaherpesviruses that could drive increased virulence. Because the live
      attenuated varicella vaccine is currently being administered to children, who in
      turn could be superinfected by wild-type VZV, this could potentiate recombination
      events of VZV as well.

PMID- 22629394
TI  - Evaluating the number of stages in development of squamous cell and
      adenocarcinomas across cancer sites using human population-based cancer modeling.
AB  - BACKGROUND: Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by
      clinical and molecular characteristics. We evaluated the characteristics of
      carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of
      various organs to test whether these characteristics differed between cancer
      subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Histotype-specific incidence rates of
      14 ACs and 12 SCCs from the SEER Registry (1973-2003) were analyzed by fitting
      several biologically motivated models to observed age patterns. A frailty model
      with the Weibull baseline was applied to each age pattern to provide the best fit
      for the majority of cancers. For each cancer, model parameters describing the
      underlying mechanisms of carcinogenesis including the number of stages occurring
      during an individual's life and leading to cancer (m-stages) were estimated. For
      sensitivity analysis, the age-period-cohort model was incorporated into the
      carcinogenesis model to test the stability of the estimates. For the majority of
      studied cancers, the numbers of m-stages were similar within each group (i.e., AC
      and SCC). When cancers of the same organs were compared (i.e., lung, esophagus,
      and cervix uteri), the number of m-stages were more strongly associated with the
      AC/SCC subtype than with the organ: 9.79+/-0.09, 9.93+/-0.19 and 8.80+/-0.10 for
      lung, esophagus, and cervical ACs, compared to 11.41+/-0.10, 12.86+/-0.34 and
      12.01+/-0.51 for SCCs of the respective organs (p<0.05 between subtypes). Most
      SCCs had more than ten m-stages while ACs had fewer than ten m-stages. The
      sensitivity analyses of the model parameters demonstrated the stability of the
      obtained estimates. CONCLUSIONS/SIGNIFICANCE: A model containing parameters
      capable of representing the number of stages of cancer development occurring
      during individual's life was applied to the large population data on incidence of
      ACs and SCCs. The model revealed that the number of m-stages differed by cancer
      subtype being more strongly associated with ACs/SCCs histotype than with
      organ/site.

PMID- 22629395
TI  - Correlation of mycobacterium tuberculosis specific and non-specific quantitative
      Th1 T-cell responses with bacillary load in a high burden setting.
AB  - BACKGROUND: Measures of bacillary load in patients with tuberculosis (TB) may be
      useful for predicting and monitoring response to treatment. The relationship
      between quantitative T-cell responses and mycobacterial load remains unclear. We
      hypothesised that, in a HIV-prevalent high burden setting, the magnitude of
      mycobacterial antigen-specific and non-specific T-cell IFN-gamma responses would
      correlate with (a) bacterial load and (b) culture conversion in patients
      undergoing treatment. METHODS: We compared baseline (n = 147), 2 (n = 35) and 6
      month (n = 13) purified-protein-derivative (PPD) and RD1-specific (TSPOT.TB and
      QFT-GIT) blood RD1-specific (TSPOT.TB; QFT-GIT) responses with associates of
      sputum bacillary load in patients with culture-confirmed TB in Cape Town, South
      Africa. RESULTS: IFN-gamma responses were not associated with liquid culture time
      to-positivity, smear-grade, Xpert MTB/RIF-generated cycle threshold values or the
      presence of cavities on the chest radiograph in patients with culture-confirmed
      TB and irrespective of HIV-status. 2-month IGRA conversion rates (positive-to
      negative) were negligible [<11% for TSPOT.TB (3/28) and QFT-GIT (1/29)] and lower
      compared to culture [60% (21/35); p<0.01]. CONCLUSIONS: In a high burden HIV
      prevalent setting T-cell IFN-gamma responses to M. tuberculosis-specific and non
      specific antigens do not correlate with bacillary load, including Xpert MTB/RIF
      generated C(T) values, and are therefore poorly suited for monitoring treatment
      and prognostication.

PMID- 22629396
TI  - Clinical significance of cartilage biomarkers for monitoring structural joint
      damage in rheumatoid arthritis patients treated with anti-TNF therapy.
AB  - PURPOSE: With the current use of biologics in rheumatoid arthritis (RA), there is
      a need to monitor ongoing structural joint damage due to the dissociation of
      articular cartilage damage from disease activity of RA. This study longitudinally
      analyzed levels of serum cartilage biomarkers during 54 weeks of infliximab
      therapy, to evaluate the feasibility of biomarkers for monitoring structural
      joint damage. METHODS: Subjects comprised 33 patients with early RA and 33
      patients with established RA. All patients received 3 mg/kg of infliximab and
      methotrexate for 54 weeks. Levels of the following serum cartilage markers were
      measured at baseline and at weeks 14, 22, and 54: hyaluronan (HA); cartilage
      oligometric matrix protein (COMP); type II collagen (CII)-related neoepitope
      (C2C); type II procollagen carboxy-propeptide (CPII); and keratin sulfate (KS).
      Time courses for each biomarker were assessed, and relationships between these
      biomarkers and clinical or radiographic parameters generally used for RA were
      investigated. RESULTS: Levels of CRP, MMP-3, DAS28-CRP, and annual progression of
      TSS were improved to similar degrees in both groups at week 54. HA and C2C/CPII
      were significantly decreased compared to baseline in the early RA group
      (p<0.001), whereas HA and COMP, but not C2C/CPII, were decreased in the
      established RA group. Strikingly, serum C2C/CPII levels were universally improved
      in early RA, regardless of EULAR response grade. Both DeltaHA and DeltaC2C/CPII
      from baseline to week 54 correlated significantly with not only DeltaCRP, but
      also DeltaDAS28 in early RA. Interestingly, when partial correlation coefficients
      were calculated by standardizing CRP levels, the significant correlation of
      DeltaHA to DeltaDAS28 disappeared, whereas correlations of DeltaC2C/CPII to
      DeltaDAS28, DeltaJNS, and DeltaHAQ remained significant. These results suggest a
      role of DeltaC2C/CPII as a marker of ongoing structural joint damage with the
      least association with CRP, and that irreversible cartilage damage in established
      RA limits restoration of the C2C/CPII level, even with tight control of joint
      inflammation. CONCLUSION: The temporal course of C2C/CPII level during anti-TNF
      therapy indicates that CII turnover shifts toward CII synthesis in early RA, but
      not in established RA, potentially due to irreversible cartilage damage.
      DeltaC2C/CPII appears to offer a useful marker reflecting ongoing structural
      joint damage, dissociated from inflammatory indices such as CRP and MMP-3.

PMID- 22629397
TI  - Baculovirus infection triggers a shift from amino acid starvation-induced
      autophagy to apoptosis.
AB  - Autophagy plays a central role in regulating important cellular functions such as
      cell survival during starvation and control of infectious pathogens. On the other
      hand, many pathogens have evolved mechanisms of inhibition of autophagy such as
      blockage of the formation of autophagosomes or the fusion of autophagosomes with
      lysosomes. Baculoviruses are important insect pathogens for pest control, and
      autophagy activity increases significantly during insect metamorphosis. However,
      it is not clear whether baculovirus infection has effects on the increased
      autophagy. In the present study, we investigated the effects of the Autographa
      californica nucleopolyhedrovirus (AcMNPV) infection on autophagy in SL-HP cell
      line from Spodoptera litura induced under amino acid deprivation. The results
      revealed that AcMNPV infection did not inhibit autophagy but triggered apoptosis
      under starvation pressure. In the early stage of infection under starvation,
      mitochondrial dysfunction was detected, suggesting the organelles might be
      involved in cell apoptosis. The semi-quantitative PCR assay revealed that the
      expression of both p35 and ie-1 genes of AcMNPV had no significant difference
      between the starved and unstarved SL-HP cells. The western blot analysis showed
      that no cleavage of endogenous Atg6 occurred during the process of apoptosis in
      SL-HP cells. These data demonstrated that some permissive insect cells may defend
      baculovirus infection via apoptosis under starvation and apoptosis is independent
      of the cleavage of Atg6 in SL-HP cells.

PMID- 22629398
TI  - The changes in maternal mortality in 1000 counties in mid-Western China by a
      government-initiated intervention.
AB  - BACKGROUND: Since 2000, the Chinese government has implemented an intervention
      program to reduce maternal mortality and eliminate neonatal tetanus in accordance
      with the Millennium Development Goals 5. To assess the effectiveness of this
      intervention program, we analyzed the level, trend and reasons defining the
      maternal mortality ratio (MMR) in the 1,000 priority counties before and after
      implementation of the intervention between 1999 and 2007. METHODOLOGY/PRINCIPAL
      FINDINGS: The data was obtained from the National Maternal and Child Health
      Routine Reporting System. The intervention included providing basic and emergency
      obstetric equipment and supplies to local medical hospitals, and also included
      providing professional training to local obstetric doctors, development of
      obstetric emergency centers and "green channel" express referral networks,
      reducing or waiving the cost of hospital delivery, and conducting community
      health education. Based on the initiation time of the intervention and the level
      of poverty, 1,000 counties, containing a total population of 300 million, were
      categorized into three groups. MMR significantly decreased by about 50%, with an
      average reduction rate of 9.24%, 16.06%, and 18.61% per year in the three county
      groups, respectively. The hospital delivery rate significantly increased.
      Obstetric hemorrhage was the leading cause of maternal deaths and significantly
      declined, with an average decrease in the MMR of 11.25%, 18.03%, and 24.90% per
      year, respectively. The magnitude of the MMR, the average reduction rate of the
      MMR, and the occurrence of the leading causes of death were closely associated
      with the percentage of poverty. CONCLUSIONS/SIGNIFICANCE: The intervention
      program implemented by the Chinese government has significantly reduced the MMR
      in mid-western China, suggesting that well-targeted interventions could be an
      efficient strategy to reducing MMR in resource-poor areas. Reduction of the MMR
      not only depends on conducting proven interventions, but also relies on economic
      development in rural areas with a high burden of maternal death.

PMID- 22629399
TI  - Who is at risk for diagnostic discrepancies? Comparison of pre- and postmortal
      diagnoses in 1800 patients of 3 medical decades in East and West Berlin.
AB  - BACKGROUND: Autopsy rates in Western countries consistently decline to an average
      of <5%, although clinical autopsies represent a reasonable tool for quality
      control in hospitals, medically and economically. Comparing pre- and postmortal
      diagnoses, diagnostic discrepancies as uncovered by clinical autopsies supply
      crucial information on how to improve clinical treatment. The study aimed at
      analyzing current diagnostic discrepancy rates, investigating their influencing
      factors and identifying risk profiles of patients that could be affected by a
      diagnostic discrepancy. METHODS AND FINDINGS: Of all adult autopsy cases of the
      Charite Institute of Pathology from the years 1988, 1993, 1998, 2003 and 2008,
      the pre- and postmortal diagnoses and all demographic data were analyzed
      retrospectively. Based on power analysis, 1,800 cases were randomly selected to
      perform discrepancy classification (class I-VI) according to modified Goldman
      criteria. The rate of discrepancies in major diagnoses (class I) was 10.7% (95%
      CI: 7.7%-14.7%) in 2008 representing a reduction by 15.1%. Subgroup analysis
      revealed several influencing factors to significantly correlate with the
      discrepancy rate. Cardiovascular diseases had the highest frequency among class-I
      discrepancies. Comparing the 1988-data of East- and West-Berlin, no significant
      differences were found in diagnostic discrepancies despite an autopsy rate
      differing by nearly 50%. A risk profile analysis visualized by intuitive heatmaps
      revealed a significantly high discrepancy rate in patients treated in low or
      intermediate care units at community hospitals. In this collective, patients with
      genitourinary/renal or infectious diseases were at particularly high risk.
      CONCLUSIONS: This is the current largest and most comprehensive study on
      diagnostic discrepancies worldwide. Our well-powered analysis revealed a
      significant rate of class-I-discrepancies indicating that autopsies are still of
      value. The identified risk profiles may aid both pathologists and clinicians to
      identify patients at increased risk for a discrepant diagnosis and possibly
      suboptimal treatment intra vitam.

PMID- 22629400
TI  - Methadone-mediated autonomic functioning of male patients with heroin dependence:
      the influence of borderline personality pattern.
AB  - BACKGROUND: We hypothesize that the population with borderline personality shows
      different autonomic response to methadone compared to individuals with other
      personalities. This study applies heart rate variability (HRV) measurements and
      the Tridimensional Personality Questionnaire (TPQ) to examine this hypothesis.
      METHODOLOGY/PRINCIPAL FINDINGS: Forty-four male patients with heroin dependence
      were recruited from a methadone maintenance treatment program. Eight personality
      patterns were classified according to the TPQ norm used in Taiwan. The borderline
      pattern (BP, composed of high novelty seeking, high harm avoidance and low reward
      dependence) and the other personality patterns (OP) were separated into two
      groups. We compared the HRV profiles between the BP and OP groups. Correlation
      and regression analysis were performed to clarify relationship between HRV
      differences and the borderline index (BI, a new concept defined by us, which is
      calculated as novelty seeking + harm avoidance - reward dependence). The HRV
      targets investigated included low frequency (LF) power, high frequency (HF)
      power, total power (TP), normalized LF (LF%), and LF/HF. No baseline HRV
      parameters showed any inter-group difference. The BP group had a significantly
      lower DeltaHF and a higher DeltaLF/HF than the OP group. The personality
      dimension, reward dependence, showed a negative correlation with DeltaLF/HF and
      DeltaLF%. BI was negatively correlated with DeltaHF and positively correlated
      with DeltaLF/HF and DeltaLF%. CONCLUSIONS/SIGNIFICANCE: Borderline personality
      individuals show increased sympathetic activity and decreased parasympathetic
      activity compared to other personalities after taking methadone. The results
      support the hypothesis that there is an interaction between borderline
      personality and autonomic modulation.

PMID- 22629401
TI  - Evaluation of genetic markers as instruments for Mendelian randomization studies
      on vitamin D.
AB  - BACKGROUND: Mendelian randomization (MR) studies use genetic variants mimicking
      the influence of a modifiable exposure to assess and quantify a causal
      association with an outcome, with an aim to avoid problems with confounding and
      reverse causality affecting other types of observational studies. AIM: We
      evaluated genetic markers that index differences in 25-hydroxyvitamin D (25(OH)D)
      as instruments for MR studies on vitamin D. METHODS AND FINDINGS: We used data
      from up-to 6,877 participants in the 1958 British birth cohort with information
      on genetic markers and 25(OH)D. As potential instruments, we selected 20 single
      nucleotide polymorphisms (SNP) which are located in the vitamin D metabolism
      pathway or affect skin pigmentation/tanning, including 4 SNPs from genome-wide
      association (GWA) meta-analyses on 25(OH)D. We analyzed SNP associations with
      25(OH)D and evaluated the use of allele scores dividing genes to those affecting
      25(OH)D synthesis (DHCR7, CYP2R1) and metabolism (GC, CYP24A1, CYP27B1). In
      addition to the GWA SNPs, only two SNPs (CYP27B1, OCA2) showed evidence for
      association with 25(OH)D, with the OCA2 association abolished after lifestyle
      adjustment. Per allele differences varied between -0.02 and -0.08 nmol/L (P<=0.02
      for all), with a 6.1 nmol/L and a 10.2 nmol/L difference in 25(OH)D between
      individuals with highest compared lowest number of risk alleles in synthesis and
      metabolism allele scores, respectively. Individual SNPs but not allele scores
      showed associations with lifestyle factors. An exception was geographical region
      which was associated with synthesis score. Illustrative power calculations (80%
      power, 5% alpha) suggest that approximately 80,000 participants are required to
      establish a causal effect of vitamin D on blood pressure using the synthesis
      allele score. CONCLUSIONS: Combining SNPs into allele scores provides a more
      powerful instrument for MR analysis than a single SNP in isolation. Population
      stratification and the potential for pleiotropic effects need to be considered in
      MR studies on vitamin D.

PMID- 22629402
TI  - TRIM16 acts as an E3 ubiquitin ligase and can heterodimerize with other TRIM
      family members.
AB  - The TRIM family of proteins is distinguished by its tripartite motif (TRIM).
      Typically, TRIM proteins contain a RING finger domain, one or two B-box domains,
      a coiled-coil domain and the more variable C-terminal domains. TRIM16 does not
      have a RING domain but does harbour two B-box domains. Here we showed that TRIM16
      homodimerized through its coiled-coil domain and heterodimerized with other TRIM
      family members; TRIM24, Promyelocytic leukaemia (PML) protein and Midline-1
      (MID1). Although, TRIM16 has no classic RING domain, three-dimensional modelling
      of TRIM16 suggested that its B-box domains adopts RING-like folds leading to the
      hypothesis that TRIM16 acts as an ubiquitin ligase. Consistent with this
      hypothesis, we demonstrated that TRIM16, devoid of a classical RING domain had
      auto-polyubiquitination activity and acted as an E3 ubiquitin ligase in vivo and
      in vitro assays. Thus via its unique structure, TRIM16 possesses both
      heterodimerization function with other TRIM proteins and also has E3 ubiquitin
      ligase activity.

PMID- 22629403
TI  - Optimizing a qPCR gene expression quantification assay for S. epidermidis
      biofilms: a comparison between commercial kits and a customized protocol.
AB  - Staphylococcus epidermidis biofilm-related infections are a current concern
      within the medical community due to their high incidence and prevalence,
      particularly in patients with indwelling medical devices. Biofilm gene expression
      analysis by quantitative real-time PCR (qPCR) has been increasingly used to
      understand the role of biofilm formation in the pathogenesis of S. epidermidis
      infections. However, depending on the RNA extraction procedure, and cDNA
      synthesis and qPCR master mixes used, gene expression quantification can be
      suboptimal. We recently showed that some RNA extraction kits are not suitable for
      S. epidermidis biofilms, due to sample composition, in particular the presence of
      the extracellular matrix. In this work, we describe a custom RNA extraction assay
      followed by the evaluation of gene expression using different commercial reverse
      transcriptase kits and qPCR master mixes. Our custom RNA extraction assay was
      able to produce good quality RNA with reproducible gene expression
      quantification, reducing the time and the costs associated. We also tested the
      effect of reducing cDNA and qPCR reaction volumes and, in most of the cases
      tested, no significant differences were found. Finally, we titered the SYBR Green
      I concentrations in standard PCR master mixes and compared the normalized
      expression of the genes icaA, bhp, aap, psmbeta1 and agrB using 4 distinct
      biofilm forming S. epidermidis strains to the results obtained with commercially
      available kits. The overall results demonstrated that despite some statistically,
      but not biologically significant differences observed, the customized qPCR
      protocol resulted in the same gene expression trend presented by the commercially
      available kits used.

PMID- 22629404
TI  - Sensitivity of PCR assays for murine gammaretroviruses and mouse contamination in
      human blood samples.
AB  - Gammaretroviruses related to murine leukemia virus (MLV) have variously been
      reported to be present or absent in blood from chronic fatigue syndrome/myalgic
      encephalomyelitis (CFS/ME) patients and healthy controls. Using subjects from New
      York State, we have investigated by PCR methods whether MLV-related sequences can
      be identified in nucleic acids isolated from whole blood or from peripheral blood
      mononuclear cells (PBMCs) or following PBMC culture. We have also passaged the
      prostate cancer cell line LNCaP following incubation with plasma from patients
      and controls and assayed nucleic acids for viral sequences. We have used 15 sets
      of primers that can effectively amplify conserved regions of murine endogenous
      and exogenous retrovirus sequences. We demonstrate that our PCR assays for MLV
      related gag sequences and for mouse DNA contamination are extremely sensitive.
      While we have identified MLV-like gag sequences following PCR on human DNA
      preparations, we are unable to conclude that these sequences originated in the
      blood samples.

PMID- 22629405
TI  - Induction of selective blood-tumor barrier permeability and macromolecular
      transport by a biostable kinin B1 receptor agonist in a glioma rat model.
AB  - Treatment of malignant glioma with chemotherapy is limited mostly because of
      delivery impediment related to the blood-brain tumor barrier (BTB). B1 receptors
      (B1R), inducible prototypical G-protein coupled receptors (GPCR) can regulate
      permeability of vessels including possibly that of brain tumors. Here, we
      determine the extent of BTB permeability induced by the natural and synthetic
      peptide B1R agonists, LysdesArg(9)BK (LDBK) and SarLys[dPhe(8)]desArg(9)BK
      (NG29), in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor
      inoculation, we detected the presence of B1R on tumor cells and associated
      vasculature. NG29 infusion increased brain distribution volume and uptake
      profiles of paramagnetic probes (Magnevist and Gadomer) at tumoral sites (T(1)
      weighted imaging). These effects were blocked by B1R antagonist and non-selective
      cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric
      oxide synthase inhibitors. Consistent with MRI data, systemic co-administration
      of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass
      spectrometry). We also detected elevated B1R expression in clinical samples of
      high-grade glioma. Our results documented a novel GPCR-signaling mechanism for
      promoting transient BTB disruption, involving activation of B1R and ensuing
      production of COX metabolites. They also underlined the potential value of
      synthetic biostable B1R agonists as selective BTB modulators for local delivery
      of different sized-therapeutics at (peri)tumoral sites.

PMID- 22629406
TI  - Ezrin ubiquitylation by the E3 ubiquitin ligase, WWP1, and consequent regulation
      of hepatocyte growth factor receptor activity.
AB  - The membrane cytoskeleton linker ezrin participates in several functions
      downstream of the receptor Met in response to Hepatocyte Growth Factor (HGF)
      stimulation. Here we report a novel interaction of ezrin with a HECT E3 ubiquitin
      ligase, WWP1/Aip5/Tiul1, a potential oncogene that undergoes genomic
      amplification and overexpression in human breast and prostate cancers. We show
      that ezrin binds to the WW domains of WWP1 via the consensus motif PPVY(477)
      present in ezrin's C-terminus. This association results in the ubiquitylation of
      ezrin, a process that requires an intact PPVY(477) motif. Interestingly ezrin
      ubiquitylation does not target the protein for degradation by the proteasome. We
      find that ezrin ubiquitylation by WWP1 in epithelial cells leads to the
      upregulation of Met level in absence of HGF stimulation and increases the
      response of Met to HGF stimulation as measured by the ability of the cells to
      heal a wound. Interestingly this effect requires ubiquitylated ezrin since it can
      be rescued, after depletion of endogenous ezrin, by wild type ezrin but not by a
      mutant of ezrin that cannot be ubiquitylated. Taken together our data reveal a
      new role for ezrin in Met receptor stability and activity through its association
      with the E3 ubiquitin ligase WWP1. Given the role of Met in cell proliferation
      and tumorigenesis, our results may provide a mechanistic basis for understanding
      the role of ezrin in tumor progression.

PMID- 22629408
TI  - Optic nerve head change in non-arteritic anterior ischemic optic neuropathy and
      its influence on visual outcome.
AB  - PURPOSE: To evaluate changes in cup/disc (C/D) diameter ratios and parapapillary
      atrophy in patients with non-arteritic anterior ischemic optic neuropathy (NA
      AION), using morphometric methods. METHODS: The clinical non-interventional study
      included 157 patients with unilateral or bilateral NA-AION. Optic disc
      photographs taken from both eyes at the end of follow-up were morphometrically
      examined. RESULTS: Follow-up was 86.3+/-70.3 months. Horizontal and vertical disc
      diameters (P = 0.30;P = 0.61, respectively), horizontal and vertical C/D ratios
      (P = 0.47;P = 0.19,resp.), and size of alpha zone and beta zone of parapapillary
      atrophy (P = 0.27;P = 0.32,resp.) did not differ significantly between affected
      eyes and contralateral normal eyes in patients with unilateral NA-AION.
      Similarly, horizontal and vertical disc diameters, horizontal and vertical C/D
      ratios, and size of alpha zone and beta zone did not vary significantly (all
      P>0.05) between the unaffected eyes of patients with unilateral NA-AION and the
      eyes of patients with bilateral NA-AION. Optic disc diameters, C/D ratios, size
      of alpha zone or beta zone of parapapillary atrophy were not significantly
      associated with final visual outcome in the eyes affected with NA-AION (all
      P>0.20) nor with the difference in final visual acuity between affected eyes and
      unaffected eyes in patients with unilateral NA-AION (all P>0.25). CONCLUSIONS: NA
      AION did not affect C/D ratios nor alpha zone and beta zone of parapapillary
      atrophy. Optic disc size was not related to the final visual acuity outcome in NA
      AION.

PMID- 22629407
TI  - Expression profiling reveals novel hypoxic biomarkers in peripheral blood of
      adult mice exposed to chronic hypoxia.
AB  - Hypoxia induces a myriad of changes including an increase in hematocrit due to
      erythropoietin (EPO) mediated erythropoiesis. While hypoxia is of importance
      physiologically and clinically, lacunae exist in our knowledge of the systemic
      and temporal changes in gene expression occurring in blood during the exposure
      and recovery from hypoxia. To identify these changes expression profiling was
      conducted on blood obtained from cohorts of C57Bl-10 wild type mice that were
      maintained at normoxia (NX), exposed for two weeks to normobaric chronic hypoxia
      (CH) or two weeks of CH followed by two weeks of normoxic recovery (REC). Using
      stringent bioinformatic cut-offs (0% FDR, 2 fold change cut-off), 230 genes were
      identified and separated into four distinct temporal categories. Class I)
      contained 1 transcript up-regulated in both CH and REC; Class II) contained 202
      transcripts up-regulated in CH but down-regulated after REC; Class III) contained
      9 transcripts down-regulated both in CH and REC; Class IV) contained 18
      transcripts down-regulated after CH exposure but up-regulated after REC.
      Profiling was independently validated and extended by analyzing expression levels
      of selected genes as novel biomarkers from our profile (e.g. spectrin alpha-1,
      ubiquitin domain family-1 and pyrroline-5-carboxylate reductase-1) by performing
      qPCR at 7 different time points during CH and REC. Our identification and
      characterization of these genes define transcriptome level changes occurring
      during chronic hypoxia and normoxic recovery as well as novel blood biomarkers
      that may be useful in monitoring a variety of physiological and pathological
      conditions associated with hypoxia.

PMID- 22629409
TI  - HGF-transgenic MSCs can improve the effects of tissue self-repair in a rabbit
      model of traumatic osteonecrosis of the femoral head.
AB  - BACKGROUND: Osteonecrosis of the femoral head (ONFH) is generally characterized
      as an irreversible disease and tends to cause permanent disability. Therefore,
      understanding the pathogenesis and molecular mechanisms of ONFH and developing
      effective therapeutic methods is critical for slowing the progress of the
      disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study, an experimental rabbit
      model of early stage traumatic ONFH was established, validated, and used for an
      evaluation of therapy. Computed tomography (CT) and magnetic resonance (MR)
      imaging confirmed that this model represents clinical Association Research
      Circulation Osseous (ARCO) phase I or II ONFH, which was also confirmed by the
      presence of significant tissue damage in osseous tissue and vasculature.
      Pathological examination detected obvious self-repair of bone tissue up to 2
      weeks after trauma, as indicated by revascularization (marked by CD105) and
      expression of collagen type I (Col I), osteocalcin, and proliferating cell
      nuclear antigen. Transplantation of hepatocyte growth factor (HGF)-transgenic
      mesenchymal stem cells (MSCs) 1 week after trauma promoted recovery from ONFH, as
      evidenced by a reversed pattern of Col I expression compared with animals
      receiving no therapeutic treatment, as well as increased expression of vascular
      endothelial growth factor. CONCLUSIONS/SIGNIFICANCE: These results indicate that
      the transplantation of HGF-transgenic MSCs is a promising method for the
      treatment for ONFH and suggest that appropriate interference therapy during the
      tissue self-repair stage contributes to the positive outcomes. This study also
      provides a model for the further study of the ONFH etiology and therapeutic
      interventions.

PMID- 22629410
TI  - Whole blood DNA aberrant methylation in pancreatic adenocarcinoma shows
      association with the course of the disease: a pilot study.
AB  - Pancreatic tumors are usually diagnosed at an advanced stage in the progression
      of the disease, thus reducing the survival chances of the patients. Non-invasive
      early detection would greatly enhance therapy and survival rates. Toward this
      aim, we investigated in a pilot study the power of methylation changes in whole
      blood as predictive markers for the detection of pancreatic tumors. We
      investigated methylation levels at selected CpG sites in the CpG rich regions at
      the promoter regions of p16, RARbeta, TNFRSF10C, APC, ACIN1, DAPK1, 3OST2, BCL2
      and CD44 in the blood of 30 pancreatic tumor patients and in the blood of 49
      matching controls. In addition, we studied LINE-1 and Alu repeats using
      degenerate amplification approach as a surrogate marker for genome-wide
      methylation. The site-specific methylation measurements at selected CpG sites
      were done by the SIRPH method. Our results show that in the patient's blood,
      tumor suppressor genes were slightly but significantly higher methylated at
      several CpG sites, while repeats were slightly less methylated compared to
      control blood. This was found to be significantly associated with higher risk for
      pancreatic ductal adenocarcinoma. Additionally, high methylation levels at
      TNFRSCF10C were associated with positive perineural spread of tumor cells, while
      higher methylation levels of TNFRSF10C and ACIN1 were significantly associated
      with shorter survival. This pilot study shows that methylation changes in blood
      could provide a promising method for early detection of pancreatic tumors.
      However, larger studies must be carried out to explore the clinical usefulness of
      a whole blood methylation based test for non-invasive early detection of
      pancreatic tumors.

PMID- 22629411
TI  - Assessment method for a power analysis to identify differentially expressed
      pathways.
AB  - Gene expression data can provide a very rich source of information for
      elucidating the biological function on the pathway level if the experimental
      design considers the needs of the statistical analysis methods. The purpose of
      this paper is to provide a comparative analysis of statistical methods for
      detecting the differentially expression of pathways (DEP). In contrast to many
      other studies conducted so far, we use three novel simulation types, producing a
      more realistic correlation structure than previous simulation methods. This
      includes also the generation of surrogate data from two large-scale microarray
      experiments from prostate cancer and ALL. As a result from our comprehensive
      analysis of 41,004 parameter configurations, we find that each method should only
      be applied if certain conditions of the data from a pathway are met. Further, we
      provide method-specific estimates for the optimal sample size for microarray
      experiments aiming to identify DEP in order to avoid an underpowered design. Our
      study highlights the sensitivity of the studied methods on the parameters of the
      system.

PMID- 22629412
TI  - Under-five mortality in high focus states in India: a district level geospatial
      analysis.
AB  - BACKGROUND: This paper examines if, when controlling for biophysical and
      geographical variables (including rainfall, productivity of agricultural lands,
      topography/temperature, and market access through road networks), socioeconomic
      and health care indicators help to explain variations in the under-five mortality
      rate across districts from nine high focus states in India. The literature on
      this subject is inconclusive because the survey data, upon which most studies of
      child mortality rely, rarely include variables that measure these factors. This
      paper introduces these variables into an analysis of 284 districts from nine high
      focus states in India. METHODOLOGY/PRINCIPAL FINDINGS: Information on the
      mortality indicator was accessed from the recently conducted Annual Health Survey
      of 2011 and other socioeconomic and geographic variables from Census 2011,
      District Level Household and Facility Survey (2007-08), Department of Economics
      and Statistics Divisions of the concerned states. Displaying high spatial
      dependence (spatial autocorrelation) in the mortality indicator (outcome
      variable) and its possible predictors used in the analysis, the paper uses the
      Spatial-Error Model in an effort to negate or reduce the spatial dependence in
      model parameters. The results evince that the coverage gap index (a mixed
      indicator of district wise coverage of reproductive and child health services),
      female literacy, urbanization, economic status, the number of newborn care
      provided in Primary Health Centers in the district transpired as significant
      correlates of under-five mortality in the nine high focus states in India. The
      study identifies three clusters with high under-five mortality rate including 30
      districts, and advocates urgent attention. CONCLUSION: Even after controlling the
      possible biophysical and geographical variables, the study reveals that the
      health program initiatives have a major role to play in reducing under-five
      mortality rate in the high focus states in India.

PMID- 22629413
TI  - Murine 3T3-L1 adipocyte cell differentiation model: validated reference genes for
      qPCR gene expression analysis.
AB  - BACKGROUND: Analysis of gene expression at the mRNA level, using real-time
      quantitative reverse transcription polymerase chain reaction (qRT-PCR),
      mandatorily requires reference genes (RGs) as internal controls. However,
      increasing evidences have shown that RG expression may vary considerably under
      experimental conditions. We sought for an appropriate panel of RGs to be used in
      the 3T3-L1 cell line model during their terminal differentiation into adipocytes.
      To this end, the expression levels of a panel of seven widely used RG mRNAs were
      measured by qRT-PCR. The 7 RGs evaluated were beta-actin (ACTB), glyceraldehyde-3
      phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyl-transferase I
      (HPRT), ATP synthase H+ transporting mitochondrial F1 complex beta subunit (ATP
      5b), tyrosine 3-monooxygenase/tryptophan 5- monooxygenase activation protein,
      zeta polypeptide (Ywhaz), Non-POU-domain containing octamer binding protein
      (NoNo), and large ribosomal protein L13a (RPL). METHODOLOGY/PRINCIPAL FINDINGS:
      Using three Excel applications, GeNorm, NormFinder and BestKeeper, we observed
      that the number and the stability of potential RGs vary significantly during
      differentiation of 3T3-L1 cells into adipocytes. mRNA expression analyses using
      qRT-PCR revealed that during the entire differentiation program, only NoNo
      expression is relatively stable. Moreover, the RG sets that were acceptably
      stable were different depending on the phase of the overall differentiation
      process (i.e. mitotic clonal expansion versus the terminal differentiation
      phase). RPL, ACTB, and Ywhaz, are suitable for terminal differentiation, whereas
      ATP-5b and HPRT, are suitable during mitotic clonal expansion. CONCLUSION: Our
      results demonstrate that special attention must be given to the choice of
      suitable RGs during the various well defined phases of adipogenesis to ensure
      accurate data analysis and that the use of several RGs is absolutely required.
      Consequently, our data show for the first time, that during mitotic clonal
      expansion, the most suitable RGs are ATP-5b, NoNo and HPRT, while during terminal
      differentiation the most suitable RGs are, NoNo, RPL, ACTB and Ywhaz.

PMID- 22629414
TI  - Bilateral sensory abnormalities in patients with unilateral neuropathic pain; a
      quantitative sensory testing (QST) study.
AB  - In patients who experience unilateral chronic pain, abnormal sensory perception
      at the non-painful side has been reported. Contralateral sensory changes in these
      patients have been given little attention, possibly because they are regarded as
      clinically irrelevant. Still, bilateral sensory changes in these patients could
      become clinically relevant if they challenge the correct identification of their
      sensory dysfunction in terms of hyperalgesia and allodynia. Therefore, we have
      used the standardized quantitative sensory testing (QST) protocol of the German
      Research Network on Neuropathic Pain (DFNS) to investigate somatosensory function
      at the painful side and the corresponding non-painful side in unilateral
      neuropathic pain patients using gender- and age-matched healthy volunteers as a
      reference cohort. Sensory abnormalities were observed across all QST parameters
      at the painful side, but also, to a lesser extent, at the contralateral, non
      painful side. Similar relative distributions regarding sensory loss/gain for non
      nociceptive and nociceptive stimuli were found for both sides. Once a sensory
      abnormality for a QST parameter at the affected side was observed, the prevalence
      of an abnormality for the same parameter at the non-affected side was as high as
      57% (for Pressure Pain Threshold). Our results show that bilateral sensory
      dysfunction in patients with unilateral neuropathic pain is more rule than
      exception. Therefore, this phenomenon should be taken into account for
      appropriate diagnostic evaluation in clinical practice. This is particularly true
      for mechanical stimuli where the 95% Confidence Interval for the prevalence of
      sensory abnormalities at the non-painful side ranges between 33% and 50%.

PMID- 22629416
TI  - Dendritic hold and read: a gated mechanism for short term information storage and
      retrieval.
AB  - Two contrasting theories have been proposed to explain the mechanistic basis of
      short term memory. One theory posits that short term memory is represented by
      persistent neural activity supported by reverberating feedback networks. An
      alternate, more recent theory posits that short term memory can be supported by
      feedforward networks. While feedback driven memory can be implemented by well
      described mechanisms of synaptic plasticity, little is known of possible
      molecular and cellular mechanisms that can implement feedforward driven memory.
      Here we report such a mechanism in which the memory trace exists in the form of
      glutamate-bound but Mg(2+)-blocked NMDA receptors on the thin terminal dendrites
      of CA1 pyramidal neurons. Because glutamate dissociates from subsets of NMDA
      receptors very slowly, excitatory synaptic transmission can leave a silent
      residual trace that outlasts the electrical activity by hundreds of milliseconds.
      Read-out of the memory trace is possible if a critical level of these bound-but
      blocked receptors accumulates on a dendritic branch that will allow these quasi
      stable receptors to sustain a regenerative depolarization when triggered by an
      independent gating signal. This process is referred to here as dendritic hold and
      read (DHR). Because the read-out of the input is not dependent on repetition of
      the input and information flows in a single-pass manner, DHR can potentially
      support a feedforward memory architecture.

PMID- 22629415
TI  - Soy isoflavones genistein and daidzein exert anti-apoptotic actions via a
      selective ER-mediated mechanism in neurons following HIV-1 Tat(1-86) exposure.
AB  - BACKGROUND: HIV-1 viral protein Tat partially mediates the neural dysfunction and
      neuronal cell death associated with HIV-1 induced neurodegeneration and
      neurocognitive disorders. Soy isoflavones provide protection against various
      neurotoxic insults to maintain neuronal function and thus help preserve
      neurocognitive capacity. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate in
      primary cortical cell cultures that 17beta-estradiol or isoflavones (genistein or
      daidzein) attenuate Tat(1-86)-induced expression of apoptotic proteins and
      subsequent cell death. Exposure of cultured neurons to the estrogen receptor
      antagonist ICI 182,780 abolished the anti-apoptotic actions of isoflavones. Use
      of ERalpha or ERbeta specific antagonists determined the involvement of both ER
      isoforms in genistein and daidzein inhibition of caspase activity; ERbeta
      selectively mediated downregulation of mitochondrial pro-apoptotic protein Bax.
      The findings suggest soy isoflavones effectively diminished HIV-1 Tat-induced
      apoptotic signaling. CONCLUSIONS/SIGNIFICANCE: Collectively, our results suggest
      that soy isoflavones represent an adjunctive therapeutic option with combination
      anti-retroviral therapy (cART) to preserve neuronal functioning and sustain
      neurocognitive abilities of HIV-1 infected persons.

PMID- 22629417
TI  - Poly(beta-amino ester)-nanoparticle mediated transfection of retinal pigment
      epithelial cells in vitro and in vivo.
AB  - A variety of genetic diseases in the retina, including retinitis pigmentosa and
      leber congenital amaurosis, might be excellent targets for gene delivery as
      treatment. A major challenge in non-viral gene delivery remains finding a safe
      and effective delivery system. Poly(beta-amino ester)s (PBAEs) have shown great
      potential as gene delivery reagents because they are easily synthesized and they
      transfect a wide variety of cell types with high efficacy in vitro. We
      synthesized a combinatorial library of PBAEs and evaluated them for transfection
      efficacy and toxicity in retinal pigment epithelial (ARPE-19) cells to identify
      lead polymer structures and transfection formulations. Our optimal polymer (B5-S5
      E7 at 60 w/w polymer:DNA ratio) transfected ARPE-19 cells with 44+/-5%
      transfection efficacy, significantly higher than with optimized formulations of
      leading commercially available reagents Lipofectamine 2000 (26+/-7%) and X
      tremeGENE HP DNA (22+/-6%); (p<0.001 for both). Ten formulations exceeded 30%
      transfection efficacy. This high non-viral efficacy was achieved with comparable
      cytotoxicity (23+/-6%) to controls; optimized formulations of Lipofectamine 2000
      and X-tremeGENE HP DNA showed 15+/-3% and 32+/-9% toxicity respectively (p>0.05
      for both). Our optimal polymer was also significantly better than a gold standard
      polymeric transfection reagent, branched 25 kDa polyethyleneimine (PEI), which
      achieved only 8+/-1% transfection efficacy with 25+/-6% cytotoxicity. Subretinal
      injections using lyophilized GFP-PBAE nanoparticles resulted in 1.1+/-1*10(3)
      fold and 1.5+/-0.7*10(3)-fold increased GFP expression in the retinal pigment
      epithelium (RPE)/choroid and neural retina respectively, compared to injection of
      DNA alone (p = 0.003 for RPE/choroid, p<0.001 for neural retina). The successful
      transfection of the RPE in vivo suggests that these nanoparticles could be used
      to study a number of genetic diseases in the laboratory with the potential to
      treat debilitating eye diseases.

PMID- 22629418
TI  - DNA sequence analyses reveal abundant diversity, endemism and evidence for Asian
      origin of the porcini mushrooms.
AB  - The wild gourmet mushroom Boletus edulis and its close allies are of significant
      ecological and economic importance. They are found throughout the Northern
      Hemisphere, but despite their ubiquity there are still many unresolved issues
      with regard to the taxonomy, systematics and biogeography of this group of
      mushrooms. Most phylogenetic studies of Boletus so far have characterized samples
      from North America and Europe and little information is available on samples from
      other areas, including the ecologically and geographically diverse regions of
      China. Here we analyzed DNA sequence variation in three gene markers from samples
      of these mushrooms from across China and compared our findings with those from
      other representative regions. Our results revealed fifteen novel phylogenetic
      species (about one-third of the known species) and a newly identified lineage
      represented by Boletus sp. HKAS71346 from tropical Asia. The phylogenetic
      analyses support eastern Asia as the center of diversity for the porcini sensu
      stricto clade. Within this clade, B. edulis is the only known holarctic species.
      The majority of the other phylogenetic species are geographically restricted in
      their distributions. Furthermore, molecular dating and geological evidence
      suggest that this group of mushrooms originated during the Eocene in eastern
      Asia, followed by dispersal to and subsequent speciation in other parts of Asia,
      Europe, and the Americas from the middle Miocene through the early Pliocene. In
      contrast to the ancient dispersal of porcini in the strict sense in the Northern
      Hemisphere, the occurrence of B. reticulatus and B. edulis sensu lato in the
      Southern Hemisphere was probably due to recent human-mediated introductions.

PMID- 22629419
TI  - Erythroid promoter confines FGF2 expression to the marrow after hematopoietic
      stem cell gene therapy and leads to enhanced endosteal bone formation.
AB  - Fibroblast growth factor-2 (FGF2) has been demonstrated to be a promising
      osteogenic factor for treating osteoporosis. Our earlier study shows that
      transplantation of mouse Sca-1(+) hematopoietic stem/progenitor cells that are
      engineered to express a modified FGF2 leads to considerable endosteal/trabecular
      bone formation, but it also induces adverse effects like hypocalemia and
      osteomalacia. Here we report that the use of an erythroid specific promoter, beta
      globin, leads to a 5-fold decrease in the ratio of serum FGF2 to the FGF2
      expression in the marrow cavity when compared to the use of a ubiquitous promoter
      spleen focus-forming virus (SFFV). The confined FGF2 expression promotes
      considerable trabeculae bone formation in endosteum and does not yield anemia and
      osteomalacia. The avoidance of anemia in the mice that received Sca1(+) cells
      transduced with FGF2 driven by the beta-globin promoter is likely due to
      attenuation of high-level serum FGF2-mediated stem cell mobilization observed in
      the SFFV-FGF2 animals. The prevention of osteomalacia is associated with
      substantially reduced serum Fgf23/hypophosphatemia, and less pronounced secondary
      hyperparathyroidism. Our improved stem cell gene therapy strategy represents one
      step closer to FGF2-based clinical therapy for systemic skeletal augmentation.

PMID- 22629420
TI  - Compliance with guidelines-recommended processes in pneumonia: impact of health
      status and initial signs.
AB  - Initial care has been associated with improved survival of community-acquired
      pneumonia (CAP). We aimed to investigate patient comorbidities and health status
      measured by the Charlson index and clinical signs at diagnosis associated with
      adherence to recommended processes of care in CAP. We studied 3844 patients
      hospitalized with CAP. The evaluated recommendations were antibiotic adherence to
      Spanish guidelines, first antibiotic dose <6 hours and oxygen assessment.
      Antibiotic adherence was 72.6%, first dose <6 h was 73.4% and oxygen assessment
      was 90.2%. Antibiotic adherence was negatively associated with a high Charlson
      score (Odds ratio [OR], 0.91), confusion (OR, 0.66) and tachycardia >=100 bpm
      (OR, 0.77). Delayed first dose was significantly lower in those with tachycardia
      (OR, 0.75). Initial oxygen assessment was negatively associated with fever (OR,
      0.61), whereas tachypnea >=30 (OR, 1.58), tachycardia (OR, 1.39), age >65 (OR,
      1.51) and COPD (OR, 1.80) were protective factors. The combination of antibiotic
      adherence and timing <6 hours was negatively associated with confusion (OR, 0.69)
      and a high Charlson score (OR, 0.92) adjusting for severity and hospital effect,
      whereas age was not an independent factor. Deficient health status and confusion,
      rather than age, are associated with lower compliance with antibiotic therapy
      recommendations and timing, thus identifying a subpopulation more prone to
      receiving lower quality care.

PMID- 22629421
TI  - Frequent occurrence of mitochondrial DNA mutations in Barrett's metaplasia
      without the presence of dysplasia.
AB  - BACKGROUND: Barrett's esophagus (BE) is one of the most common premalignant
      lesions and can progress to esophageal adenocarcinoma (EA). The numerous
      molecular events may play a role in the neoplastic transformation of Barrett's
      mucosa such as the change of DNA ploidy, p53 mutation and alteration of adhesion
      molecules. However, the molecular mechanism of the progression of BE to EA
      remains unclear and most studies of mitochondrial DNA (mtDNA) mutations in BE
      have performed on BE with the presence of dysplasia. METHODS/FINDINGS: Thus, the
      current study is to investigate new molecular events (Barrett's esophageal tissue
      specific-mtDNA alterations/instabilities) in mitochondrial genome and causative
      factors for their alterations using the corresponding adjacent normal mucosal
      tissue (NT) and tissue (BT) from 34 patients having Barrett's metaplasia without
      the presence of dysplasia. Eighteen patients (53%) exhibited mtDNA mutations
      which were not found in adjacent NT. mtDNA copy number was about 3 times higher
      in BT than in adjacent NT. The activity of the mitochondrial respiratory chain
      enzyme complexes in tissues from Barrett's metaplasia without the presence of
      dysplasia was impaired. Reactive oxygen species (ROS) level in BT was
      significantly higher than those in corresponding samples.
      CONCLUSION/SIGNIFICANCE: High ROS level in BT may contribute to the development
      of mtDNA mutations, which may play a crucial role in disease progression and
      tumorigenesis in BE.

PMID- 22629422
TI  - Oxygen-glucose deprivation induced glial scar-like change in astrocytes.
AB  - BACKGROUND: It has been demonstrated that cerebral ischemia induces astrocyte
      reactivity, and subsequent glial scar formation inhibits axonal regeneration
      during the recovery phase. Investigating the mechanism of glial scar formation
      will facilitate the development of strategies to improve axonal regeneration.
      However, an in vitro model of ischemia-induced glial scar has not yet been
      systematically established. METHODOLOGY AND PRINCIPAL FINDINGS: In the present
      study, we at the first time found that oxygen-glucose deprivation (OGD) in vitro
      can induce rat cortical astrocytes to present characteristics of glial scar.
      After OGD for 6 h, astrocytes showed a remarkable proliferation following 24 h
      reperfusion, evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay and BrdU immunocytochemistry. Meanwhile, the expression of glial
      fibrillary acidic protein significantly increased, so did the expression of
      neurocan, which is a hallmark of the glial scar. In further experiments, neurons
      were co-cultured with astrocytes, which had been exposed to OGD, and then the
      immunostaining of class III beta-tubulin was carried out to assess the neurite
      growth. When the co-culture was performed at 48 h reperfusion of astrocytes, the
      neurite growth was obviously inhibited, and this inhibition could be reversed by
      chondroitinase ABC, which digests glycosaminoglycan chains on CSPGs, including
      neurocan. However, the processes of neurons were elongated, when the co-culture
      was performed immediately after OGD. CONCLUSIONS AND SIGNIFICANCE: Our results
      indicated that after conditioned OGD the astrocytes presented the characteristics
      of the glial scar, which are also comparable to the astrocytes in acute and
      chronic phases after cerebral ischemia in vivo. Therefore, the present system may
      be used as an in vitro model to explore the mechanisms underlying glial scar
      formation and the treatments to improve axonal regeneration after cerebral
      ischemia.

PMID- 22629423
TI  - Twelve positions in a beta-lactamase that can expand its substrate spectrum with
      a single amino acid substitution.
AB  - The continuous evolution of beta-lactamases resulting in bacterial resistance to
      beta-lactam antibiotics is a major concern in public health, and yet the
      underlying molecular basis or the pattern of such evolution is largely unknown.
      We investigated the mechanics of the substrate fspectrum expansion of the class A
      beta-lactamase using PenA of Burkholderia thailandensis as a model. By analyzing
      516 mutated enzymes that acquired the ceftazidime-hydrolyzing activity, we found
      twelve positions with single amino acid substitutions (altogether twenty-nine
      different substitutions), co-localized at the active-site pocket area. The
      ceftazidime MIC (minimum inhibitory concentration) levels and the relative
      frequency in the occurrence of substitutions did not correlate well with each
      other, and the latter appeared be largely influenced by the intrinsic mutational
      biases present in bacteria. Simulation studies suggested that all substitutions
      caused a congruent effect, expanding the space in a conserved structure called
      the omega loop, which in turn increased flexibility at the active site. A second
      phase of selection, in which the mutants were placed under increased antibiotic
      pressure, did not result in a second mutation in the coding region, but a
      mutation that increased gene expression arose in the promoter. This result
      suggests that the twelve amino acid positions and their specific substitutions in
      PenA may represent a comprehensive repertoire of the enzyme's adaptability to a
      new substrate. These mapped substitutions represent a comprehensive set of
      general mechanical paths to substrate spectrum expansion in class A beta
      lactamases that all share a functional evolutionary mechanism using common
      conserved residues.

PMID- 22629424
TI  - A2 noradrenergic lesions prevent renal sympathoinhibition induced by
      hypernatremia in rats.
AB  - Renal vasodilation and sympathoinhibition are recognized responses induced by
      hypernatremia, but the central neural pathways underlying such responses are not
      yet entirely understood. Several findings suggest that A2 noradrenergic neurons,
      which are found in the nucleus of the solitary tract (NTS), play a role in the
      pathways that contribute to body fluid homeostasis and cardiovascular regulation.
      The purpose of this study was to determine the effects of selective lesions of A2
      neurons on the renal vasodilation and sympathoinhibition induced by hypertonic
      saline (HS) infusion. Male Wistar rats (280-350 g) received an injection into the
      NTS of anti-dopamine-beta-hydroxylase-saporin (A2 lesion; 6.3 ng in 60 nl; n = 6)
      or free saporin (sham; 1.3 ng in 60 nl; n = 7). Two weeks later, the rats were
      anesthetized (urethane 1.2 g?kg(-1) b.wt., i.v.) and the blood pressure, renal
      blood flow (RBF), renal vascular conductance (RVC) and renal sympathetic nerve
      activity (RSNA) were recorded. In sham rats, the HS infusion (3 M NaCl, 1.8
      ml?kg(-1) b.wt., i.v.) induced transient hypertension (peak at 10 min after HS;
      9+/-2.7 mmHg) and increases in the RBF and RVC (141+/-7.9% and 140+/-7.9% of
      baseline at 60 min after HS, respectively). HS infusion also decreased the RSNA (
      45+/-5.0% at 10 min after HS) throughout the experimental period. In the A2
      lesioned rats, the HS infusion induced transient hypertension (6+/-1.4 mmHg at 10
      min after HS), as well as increased RBF and RVC (133+/-5.2% and 134+/-6.9% of
      baseline at 60 min after HS, respectively). However, in these rats, the HS failed
      to reduce the RSNA (115+/-3.1% at 10 min after HS). The extent of the
      catecholaminergic lesions was confirmed by immunocytochemistry. These results
      suggest that A2 noradrenergic neurons are components of the neural pathways
      regulating the composition of the extracellular fluid compartment and are
      selectively involved in hypernatremia-induced sympathoinhibition.

PMID- 22629425
TI  - Chondroitinase and growth factors enhance activation and oligodendrocyte
      differentiation of endogenous neural precursor cells after spinal cord injury.
AB  - The adult spinal cord harbours a population of multipotent neural precursor cells
      (NPCs) with the ability to replace oligodendrocytes. However, despite this
      capacity, proliferation and endogenous remyelination is severely limited after
      spinal cord injury (SCI). In the post-traumatic microenvironment following SCI,
      endogenous spinal NPCs mainly differentiate into astrocytes which could
      contribute to astrogliosis that exacerbate the outcomes of SCI. These findings
      emphasize a key role for the post-SCI niche in modulating the behaviour of spinal
      NPCs after SCI. We recently reported that chondroitin sulphate proteoglycans
      (CSPGs) in the glial scar restrict the outcomes of NPC transplantation in SCI by
      reducing the survival, migration and integration of engrafted NPCs within the
      injured spinal cord. These inhibitory effects were attenuated by administration
      of chondroitinase (ChABC) prior to NPC transplantation. Here, in a rat model of
      compressive SCI, we show that perturbing CSPGs by ChABC in combination with
      sustained infusion of growth factors (EGF, bFGF and PDGF-AA) optimize the
      activation and oligodendroglial differentiation of spinal NPCs after injury. Four
      days following SCI, we intrathecally delivered ChABC and/or GFs for seven days.
      We performed BrdU incorporation to label proliferating cells during the treatment
      period after SCI. This strategy increased the proliferation of spinal NPCs,
      reduced the generation of new astrocytes and promoted their differentiation along
      an oligodendroglial lineage, a prerequisite for remyelination. Furthermore, ChABC
      and GF treatments enhanced the response of non-neural cells by increasing the
      generation of new vascular endothelial cells and decreasing the number of
      proliferating macrophages/microglia after SCI. In conclusions, our data strongly
      suggest that optimization of the behaviour of endogenous spinal NPCs after SCI is
      critical not only to promote endogenous oligodendrocyte replacement, but also to
      reverse the otherwise detrimental effects of their activation into astrocytes
      which could negatively influence the repair process after SCI.

PMID- 22629426
TI  - Target cueing provides support for target- and resource-based models of the
      attentional blink.
AB  - The attentional blink (AB) describes a time-based deficit in processing the
      second of two masked targets. The AB is attenuated if successive targets appear
      between the first and final target, or if a cueing target is positioned before
      the final target. Using various speeds of stimulus presentation, the current
      study employed successive targets and cueing targets to confirm and extend an
      understanding of target-target cueing in the AB. In Experiment 1, three targets
      were presented sequentially at rates of 30 msec/item or 90 msec/item. Successive
      targets presented at 90 msec improved performance compared with non-successive
      targets. However, accuracy was equivalently high for successive and non
      successive targets presented at 30 msec/item, suggesting that--regardless of
      whether they occurred consecutively--those items fell within the temporally
      defined attentional window initiated by the first target. Using four different
      presentation speeds, Experiment 2 confirmed the time-based definition of the AB
      and the success of target-cueing at 30 msec/item. This experiment additionally
      revealed that cueing was most effective when resources were not devoted to the
      cue, thereby implicating capacity limitations in the AB. Across both experiments,
      a novel order-error measure suggested that errors tend to decrease with an
      increasing duration between the targets, but also revealed that certain stimulus
      conditions result in stable order accuracy. Overall, the results are best
      encapsulated by target-based and resource-sharing theories of the AB, which
      collectively value the contributions of capacity limitations and optimizing
      transient attention in time.

PMID- 22629427
TI  - Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens
      junctions by regulating SHP2.
AB  - BACKGROUND: The fibroblast growth factor (FGF) system plays a critical role in
      the maintenance of vascular integrity via enhancing the stability of VE-cadherin
      at adherens junctions. However, the precise molecular mechanism is not well
      understood. In the present study, we aimed to investigate the detailed mechanism
      of FGF regulation of VE-cadherin function that leads to endothelial junction
      stabilization. METHODS AND FINDINGS: In vitro studies demonstrated that the loss
      of FGF signaling disrupts the VE-cadherin-catenin complex at adherens junctions
      by increasing tyrosine phosphorylation levels of VE-cadherin. Among protein
      tyrosine phosphatases (PTPs) known to be involved in the maintenance of the VE
      cadherin complex, suppression of FGF signaling reduces SHP2 expression levels and
      SHP2/VE-cadherin interaction due to accelerated SHP2 protein degradation.
      Increased endothelial permeability caused by FGF signaling inhibition was rescued
      by SHP2 overexpression, indicating the critical role of SHP2 in the maintenance
      of endothelial junction integrity. CONCLUSIONS: These results identify FGF
      dependent maintenance of SHP2 as an important new mechanism controlling the
      extent of VE-cadherin tyrosine phosphorylation, thereby regulating its presence
      in adherens junctions and endothelial permeability.

PMID- 22629428
TI  - Dysregulation of microRNA-34a expression in head and neck squamous cell carcinoma
      promotes tumor growth and tumor angiogenesis.
AB  - BACKGROUND: MicroRNAs (miRs) are small non-coding RNAs that play an important
      role in cancer development where they can act as oncogenes or as tumor
      suppressors. miR-34a is a tumor-suppressor that is frequently downregulated in a
      number of tumor types. However, little is known about the role of miR-34a in head
      and neck squamous cell carcinoma (HNSCC). METHODS AND RESULTS: miR-34a expression
      in tumor samples, HNSCC cell lines and endothelial cells was examined by real
      time PCR. Lipofectamine-2000 was used to transfect miR-34a in HNSCC cell lines
      and human endothelial cells. Cell-proliferation, migration and clonogenic
      survival was examined by MTT, Xcelligence system, scratch assay and colony
      formation assay. miR-34a effect on tumor growth and tumor angiogenesis was
      examined by in vivo SCID mouse xenograft model. Our results demonstrate that miR
      34a is significantly downregulated in HNSCC tumors and cell lines. Ectopic
      expression of miR-34a in HNSCC cell lines significantly inhibited tumor cell
      proliferation, colony formation and migration. miR-34a overexpression also
      markedly downregulated E2F3 and survivin levels. Rescue experiments using
      microRNA resistant E2F3 isoforms suggest that miR-34a-mediated inhibition of cell
      proliferation and colony formation is predominantly mediated by E2F3a isoform. In
      addition, tumor samples from HNSCC patients showed an inverse relationship
      between miR-34a and survivin as well as miR-34a and E2F3 levels. Overexpression
      of E2F3a completely rescued survivin expression in miR-34a expressing cells,
      thereby suggesting that miR-34a may be regulating survivin expression via E2F3a.
      Ectopic expression of miR-34a also significantly inhibited tumor growth and tumor
      angiogenesis in a SCID mouse xenograft model. Interestingly, miR-34a inhibited
      tumor angiogenesis by blocking VEGF production by tumor cells as well as directly
      inhibiting endothelial cell functions. CONCLUSIONS: Taken together, these
      findings suggest that dysregulation of miR-34a expression is common in HNSCC and
      modulation of miR34a activity might represent a novel therapeutic strategy for
      the treatment of HNSCC.

PMID- 22629429
TI  - Macrophage migration inhibitory factor induces autophagy via reactive oxygen
      species generation.
AB  - Autophagy is an evolutionarily conserved catabolic process that maintains
      cellular homeostasis under stress conditions such as starvation and pathogen
      infection. Macrophage migration inhibitory factor (MIF) is a multifunctional
      cytokine that plays important roles in inflammation and tumorigenesis. Cytokines
      such as IL-1beta and TNF-alpha that are induced by MIF have been shown to be
      involved in the induction of autophagy. However, the actual role of MIF in
      autophagy remains unclear. Here, we have demonstrated that incubation of human
      hepatoma cell line HuH-7 cells with recombinant MIF (rMIF) induced reactive
      oxygen species (ROS) production and autophagy formation, including LC3-II
      expression, LC3 punctae formation, autophagic flux, and mitochondria membrane
      potential loss. The autophagy induced by rMIF was inhibited in the presence of
      MIF inhibitor, ISO-1 as well as ROS scavenger N-acetyl-L-cysteine (NAC). In
      addition, serum starvation-induced MIF release and autophagy of HuH-7 cells were
      partly blocked in the presence of NAC. Moreover, diminished MIF expression by
      shRNA transfection or inhibition of MIF by ISO-1 decreased serum starvation
      induced autophagy of HuH-7 cells. Taken together, these data suggest that cell
      autophagy was induced by MIF under stress conditions such as inflammation and
      starvation through ROS generation.

PMID- 22629430
TI  - Pre-existing diseases of patients increase susceptibility to hypoxemia during
      gastrointestinal endoscopy.
AB  - Hypoxemia is the most common adverse event that happened during gastrointestinal
      endoscopy. To estimate risk of hypoxemia prior to endoscopy, American Society of
      Anesthesiology (ASA) classification scores were used as a major predictive
      factor. But the accuracy of ASA scores for predicting hypoxemia incidence was
      doubted here, considering that the classification system ignores much information
      about general health status and fitness of patient that may contribute to
      hypoxemia. In this retrospective review of clinical data collected prospectively,
      the data on 4904 procedures were analyzed. The Pearson's chi-square test or the
      Fisher exact test was employed to analyze variance of categorical factors.
      Continuous variables were statistically evaluated using t-tests or Analysis of
      variance (ANOVA). As a result, only 245 (5.0%) of the enrolled 4904 patients were
      found to present hypoxemia during endoscopy. Multivariable logistic regressions
      revealed that independent risk factors for hypoxemia include high BMI (BMI 30
      versus 20, Odd ratio: 1.52, 95% CI: 1.13-2.05; P = 0.0098), hypertension (Odd
      ratio: 2.28, 95% CI: 1.44-3.60; P = 0.0004), diabetes (Odd ratio: 2.37, 95% CI:
      1.30-4.34; P = 0.005), gastrointestinal diseases (Odd ratio: 1.77, 95% CI: 1.21
      2.60; P = 0.0033), heart diseases (Odd ratio: 1.97, 95% CI: 1.06-3.68; P =
      0.0325) and the procedures that combined esophagogastroduodenoscopy (EGD) and
      colonoscopy (Odd ratio: 4.84, 95% CI: 1.61-15.51; P = 0.0292; EGD as reference).
      It is noteworthy that ASA classification scores were not included as an
      independent predictive factor, and susceptibility of youth to hypoxemia during
      endoscopy was as high as old subjects. In conclusion, some certain pre-existing
      diseases of patients were newly identified as independent risk factors for
      hypoxemia during GI endoscopy. High ASA scores are a confounding predictive
      factor of pre-existing diseases. We thus recommend that youth (<=18 yrs), obese
      patients and those patients with hypertension, diabetes, heart diseases, or GI
      diseases should be monitored closely during sedation endoscopy.

PMID- 22629431
TI  - Three-dimensional noninvasive monitoring iodine-131 uptake in the thyroid using a
      modified Cerenkov luminescence tomography approach.
AB  - BACKGROUND: Cerenkov luminescence tomography (CLT) provides the three-dimensional
      (3D) radiopharmaceutical biodistribution in small living animals, which is vital
      to biomedical imaging. However, existing single-spectral and multispectral
      methods are not very efficient and effective at reconstructing the distribution
      of the radionuclide tracer. In this paper, we present a semi-quantitative
      Cerenkov radiation spectral characteristic-based source reconstruction method
      named the hybrid spectral CLT, to efficiently reconstruct the radionuclide tracer
      with both encouraging reconstruction results and less acquisition and image
      reconstruction time. METHODOLOGY/PRINCIPAL FINDINGS: We constructed the
      implantation mouse model implanted with a 400 uCi Na(131)I radioactive source and
      the physiological mouse model received an intravenous tail injection of 400 uCi
      radiopharmaceutical Iodine-131 (I-131) to validate the performance of the hybrid
      spectral CLT and compared the reconstruction results, acquisition, and image
      reconstruction time with that of single-spectral and multispectral CLT.
      Furthermore, we performed 3D noninvasive monitoring of I-131 uptake in the
      thyroid and quantified I-131 uptake in vivo using hybrid spectral CLT. Results
      showed that the reconstruction based on the hybrid spectral CLT was more accurate
      in localization and quantification than using single-spectral CLT, and was more
      efficient in the in vivo experiment compared with multispectral CLT.
      Additionally, 3D visualization of longitudinal observations suggested that the
      reconstructed energy of I-131 uptake in the thyroid increased with acquisition
      time and there was a robust correlation between the reconstructed energy versus
      the gamma ray counts of I-131 (r(2) = 0.8240). The ex vivo biodistribution
      experiment further confirmed the I-131 uptake in the thyroid for hybrid spectral
      CLT. CONCLUSIONS/SIGNIFICANCE: Results indicated that hybrid spectral CLT could
      be potentially used for thyroid imaging to evaluate its function and monitor its
      treatment for thyroid cancer.

PMID- 22629433
TI  - Modelling a historic oil-tank fire allows an estimation of the sensitivity of the
      infrared receptors in pyrophilous Melanophila beetles.
AB  - Pyrophilous jewel beetles of the genus Melanophila approach forest fires and
      there is considerable evidence that these beetles can detect fires from great
      distances of more than 60 km. Because Melanophila beetles are equipped with
      infrared receptors and are also attracted by hot surfaces it can be concluded
      that these infrared receptors are used for fire detection.The sensitivity of the
      IR receptors is still unknown. The lowest threshold published so far is 0.6
      W/m(2) which, however, cannot explain the detection of forest fires by IR
      radiation from distances larger than approximately 10 km. To investigate the
      possible sensitivity of the IR receptors we assumed that beetles use IR radiation
      for remote fire detection and we made use of a historic report about a big oil
      tank fire in Coalinga, California, in 1924. IR emission of an oil-tank fire can
      be calculated by "pool fire" simulations which now are used for fire safety and
      risk analysis. Assuming that beetles were lured to the fire from the nearest
      forests 25 and 130 km away, our results show that detection from a distance of 25
      km requires a threshold of the IR receptors of at least 3*10(-2) W/m(2).
      According to our investigations most beetles became aware of the fire from a
      distance of 130 km. In this case the threshold has to be 1.3*10(-4) W/m(2).
      Because such low IR intensities are buried in thermal noise we suggest that the
      infrared sensory system of Melanophila beetles utilizes stochastic resonance for
      the detection of weak IR radiation. Our simulations also suggest that the
      biological IR receptors might be even more sensitive than uncooled technical IR
      sensors. Thus a closer look into the mode of operation of the Melanophila IR
      receptors seems promising for the development of novel IR sensors.

PMID- 22629432
TI  - Impact of rituximab on immunoglobulin concentrations and B cell numbers after
      cyclophosphamide treatment in patients with ANCA-associated vasculitides.
AB  - OBJECTIVE: To assess the impact of immunosuppressive therapy with
      cyclophosphamide (CYC) and rituximab (RTX) on serum immunoglobulin (Ig)
      concentrations and B lymphocyte counts in patients with ANCA-associated
      vasculitides (AAVs). METHODS: Retrospective analysis of Ig concentrations and
      peripheral B cell counts in 55 AAV patients. RESULTS: CYC treatment resulted in a
      decrease in Ig levels (median; interquartile range IQR) from IgG 12.8 g/L (8.15
      15.45) to 9.17 g/L (8.04-9.90) (p = 0.002), IgM 1.05 g/L (0.70-1.41) to 0.83 g/L
      (0.60-1.17) (p = 0.046) and IgA 2.58 g/L (1.71-3.48) to 1.58 g/L (1-31-2.39) (p =
      0.056) at a median follow-up time of 4 months. IgG remained significantly below
      the initial value at 14.5 months and 30 months analyses. Subsequent RTX treatment
      in patients that had previously received CYC resulted in a further decline in Ig
      levels from pre RTX IgG 9.84 g/L (8.71-11.60) to 7.11 g/L (5.75-8.77; p = 0.007),
      from pre RTX IgM 0.84 g/L (0.63-1.18) to 0.35 g/L (0.23-0.48; p<0.001) and from
      pre RTX IgA 2.03 g/L (1.37-2.50) to IgA 1.62 g/L (IQR 0.84-2.43; p = 0.365) 14
      months after RTX. Treatment with RTX induced a complete depletion of B cells in
      all patients. After a median observation time of 20 months median B lymphocyte
      counts remained severely suppressed (4 B-cells/ul, 1.25-9.5, p<0.001). Seven
      patients (21%) that had been treated with CYC followed by RTX were started on Ig
      replacement because of severe bronchopulmonary infections and serum IgG
      concentrations below 5 g/L. CONCLUSIONS: In patients with AAVs, treatment with
      CYC leads to a decline in immunoglobulin concentrations. A subsequent RTX therapy
      aggravates the decline in serum immunoglobulin concentrations and results in a
      profoundly delayed B cell repopulation. Surveying patients with AAVs post CYC and
      RTX treatment for serum immunoglobulin concentrations and persisting
      hypogammaglobulinemia is warranted.

PMID- 22629434
TI  - Differential gene expression in the EphA4 knockout spinal cord and analysis of
      the inflammatory response following spinal cord injury.
AB  - Mice lacking the axon guidance molecule EphA4 have been shown to exhibit
      extensive axonal regeneration and functional recovery following spinal cord
      injury. To assess mechanisms by which EphA4 may modify the response to neural
      injury a microarray was performed on spinal cord tissue from mice with spinal
      cord injury and sham injured controls. RNA was purified from spinal cords of
      adult EphA4 knockout and wild-type mice four days following lumbar spinal cord
      hemisection or laminectomy only and was hybridised to Affymetrix All-Exon Array
      1.0 GeneChipsTM. While subsequent analyses indicated that several pathways were
      altered in EphA4 knockout mice, of particular interest was the attenuated
      expression of a number of inflammatory genes, including Arginase 1, expression of
      which was lower in injured EphA4 knockout compared to wild-type mice.
      Immunohistological analyses of different cellular components of the immune
      response were then performed in injured EphA4 knockout and wildtype spinal cords.
      While numbers of infiltrating CD3+ T cells were low in the hemisection model, a
      robust CD11b+ macrophage/microglial response was observed post-injury. There was
      no difference in the overall number or spread of macrophages/activated microglia
      in injured EphA4 knockout compared to wild-type spinal cords at 2, 4 or 14 days
      post-injury, however a lower proportion of Arginase-1 immunoreactive
      macrophages/activated microglia was observed in EphA4 knockout spinal cords at 4
      days post-injury. Subtle alterations in the neuroinflammatory response in injured
      EphA4 knockout spinal cords may contribute to the regeneration and recovery
      observed in these mice following injury.

PMID- 22629435
TI  - Macular thickness by age and gender in healthy eyes using spectral domain optical
      coherence tomography.
AB  - PURPOSE: To determine normal macular thickness and its variation by age and
      gender in healthy eyes using spectral-domain optical coherence tomography (SD
      OCT). METHODS: In this cross-sectional analysis, two hundred and twenty eyes of
      220 healthy subjects underwent raster scanning using Topcon SD-OCT system, at the
      Department of Ophthalmology, Dow University of Health Sciences and Civil Hospital
      Karachi, Pakistan. Macular thickness from all 9 regions of the ETDRS map was
      documented for each subject. Variations in macular thickness measurements by age
      and gender were determined. RESULTS: The 220 subjects had a mean age of 45.3
      years (16-80 years). Using the ETDRS map, foveal thickness for all subjects was
      measured to be 229+/-20.46 um. Mean macular thickness for all subjects was
      262.8+/-13.34 um. Male gender was associated with greater foveal (p<0.0001) and
      mean macular (p<0.0001) thickness compared to females. There was no association
      of mean macular thickness (r(2) = 0.01; p>0.05) and foveal thickness (r(2) =
      0.00004; p>0.05) with age. CONCLUSION: We have provided normative data for
      macular thickness using Topcon SD-OCT system. Our results are comparable to some
      and vary from other reports using the similar OCT system. Our results suggest
      that male gender is associated with greater macular thickness, while macular
      thickness has no association with age in healthy eyes. This is the first
      normative data for macular thickness from Pakistan; benchmark for diagnosing and
      monitoring macular pathologies. The values obtained in this study may be useful
      for comparison with other populations, other SD-OCT systems and future imaging
      technologies.

PMID- 22629436
TI  - Additive and transcript-specific effects of KPAP1 and TbRND activities on 3' non
      encoded tail characteristics and mRNA stability in Trypanosoma brucei.
AB  - Short, non-encoded oligo(A), oligo(U), or A/U tails can impact mRNA stability in
      kinetoplastid mitochondria. However, a comprehensive picture of the relative
      effects of these modifications in RNA stability is lacking. Furthermore, while
      the U-preferring exoribonuclease TbRND acts on U-tailed gRNAs, its role in decay
      of uridylated mRNAs has only been cursorily investigated. Here, we analyzed the
      roles of mRNA 3' tail composition and TbRND in RNA decay using cells harbouring
      single or double knockdown of TbRND and the KPAP1 poly(A) polymerase. Analysis of
      mRNA abundance and tail composition reveals dramatic and transcript-specific
      effects of adenylation and uridylation on mitochondrial RNAs. Oligo(A) and A-rich
      tails can stabilize a proportion of edited and never-edited RNAs. However, non
      tailed RNAs are not inherently unstable, implicating additional stability
      determinants and/or spatial segregation of sub-populations of a given RNA in
      regulation of RNA decay. Oligo(U) tails, which have been shown to contribute to
      decay of some never-edited RNAs, are not universally destabilizing. We also show
      that RNAs display very different susceptibility to uridylation in the absence of
      KPAP1, a factor that may contribute to regulation of decay. Finally, 3' tail
      composition apparently impacts the ability of an RNA to be edited.

PMID- 22629437
TI  - The MSX1 homeoprotein recruits G9a methyltransferase to repressed target genes in
      myoblast cells.
AB  - Although the significance of lysine modifications of core histones for regulating
      gene expression is widely appreciated, the mechanisms by which these
      modifications are incorporated at specific regulatory elements during cellular
      differentiation remains largely unknown. In our previous studies, we have shown
      that in developing myoblasts the Msx1 homeoprotein represses gene expression by
      influencing the modification status of chromatin at its target genes. We now show
      that genomic binding by Msx1 promotes enrichment of the H3K9me2 mark on repressed
      target genes via recruitment of G9a histone methyltransferase, the enzyme
      responsible for catalyzing this histone mark. Interaction of Msx1 with G9a is
      mediated via the homeodomain and is required for transcriptional repression and
      regulation of cellular differentiation, as well as enrichment of the H3K9me2 mark
      in proximity to Msx1 binding sites on repressed target genes in myoblast cells as
      well as the developing limb. We propose that regulation of chromatin status by
      Msx1 recruitment of G9a and other histone modifying enzymes to regulatory regions
      of target genes represents an important means of regulating the gene expression
      during development.

PMID- 22629438
TI  - Increased urinary angiotensin-converting enzyme 2 in renal transplant patients
      with diabetes.
AB  - Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a
      renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2
      has been detected in urine from patients with chronic kidney disease. We measured
      urinary ACE2 activity and protein levels in renal transplant patients (age 54
      yrs, 65% male, 38% diabetes, n = 100) and healthy controls (age 45 yrs, 26% male,
      n = 50), and determined factors associated with elevated urinary ACE2 in the
      patients. Urine from transplant subjects was also assayed for ACE mRNA and
      protein. No subjects were taking inhibitors of the renin-angiotensin system.
      Urinary ACE2 levels were significantly higher in transplant patients compared to
      controls (p = 0.003 for ACE2 activity, and p<=0.001 for ACE2 protein by ELISA or
      western analysis). Transplant patients with diabetes mellitus had significantly
      increased urinary ACE2 activity and protein levels compared to non-diabetics
      (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and
      protein were significantly increased in diabetic transplant subjects, while ACE
      mRNA levels did not differ from non-diabetic subjects. After adjusting for
      confounding variables, diabetes was significantly associated with urinary ACE2
      activity (p = 0.003) and protein levels (p<0.001), while female gender was
      associated with urinary mRNA levels for both ACE2 and ACE. These data indicate
      that urinary ACE2 is increased in renal transplant recipients with diabetes,
      possibly due to increased shedding from tubular cells. Urinary ACE2 could be a
      marker of renal renin-angiotensin system activation in these patients.

PMID- 22629439
TI  - Incremental yield of serial sputum cultures for diagnosis of tuberculosis among
      HIV infected smear negative pulmonary TB suspects in Kampala, Uganda.
AB  - BACKGROUND: Sputum culture is the gold standard for diagnosis of pulmonary
      tuberculosis (PTB). Although mostly used for research, culture is recommended by
      the World Health Organization for TB diagnosis among HIV infected smear negative
      PTB suspects. Even then, the number of sputum samples required remains
      unspecified. Here, we determined the Incremental Yield (IY) and number of samples
      required to diagnose an additional PTB case upon second and third serial sputum
      culture. METHODS/FINDINGS: This was a cross sectional study done between January
      and March 2011. Serial sputum samples were provided by participants within two
      days and cultured using Lowenstein Jensen (LJ) and Mycobacteria Growth Indicator
      Tube (MGIT) methods. A PTB case was defined as a positive culture on either one
      or both methods. The IY from the second and third serial cultures was determined
      and the reciprocal of the product of the fractions of IY provided the number of
      samples required for an additional PTB case. Of the 170 smear negative PTB
      suspects, 62 (36.5%) met the case definition. The IY of the second sample culture
      was 12.7%, 23.6% and 12.6% and for the third sample culture was 6.8%, 7.5% and
      7.3% with LJ, MGIT and LJ or MGIT, respectively. The number of samples required
      for an additional PTB case and 95% CI upon the second sample culture were 29.9
      (16.6, 156.5), 11.3 (7.6, 21.9) and 20.8 (12.5, 62.7); while for the third sample
      culture were 55.6 (26.4, 500.4), 35.7 (19.0, 313.8) and 36.1 (19.1, 330.9) by LJ,
      MGIT and LJ or MGIT respectively. CONCLUSIONS/SIGNIFICANCE: Among HIV infected
      smear negative PTB suspects in Kampala, 93% of PTB cases are diagnosed upon the
      second serial sputum culture. The number of cultures needed to diagnose an
      additional PTB case, ranges from 11-30 and 35-56 by the second and third sputum
      samples, respectively.

PMID- 22629440
TI  - Integrative miRNA-mRNA profiling of adipose tissue unravels transcriptional
      circuits induced by sleep fragmentation.
AB  - Obstructive sleep apnea (OSA) is a prevalent condition and strongly associated
      with metabolic disorders. Sleep fragmentation (SF) is a major consequence of OSA,
      but its contribution to OSA-related morbidities is not known. We hypothesized
      that SF causes specific perturbations in transcriptional networks of visceral fat
      cells, leading to systemic metabolic disturbances. We simultaneously profiled
      visceral adipose tissue mRNA and miRNA expression in mice exposed to 6 hours of
      SF during sleep, and developed a new computational framework based on gene set
      enrichment and network analyses to merge these data. This approach leverages
      known gene product interactions and biologic pathways to interrogate large-scale
      gene expression profiling data. We found that SF induced the activation of
      several distinct pathways, including those involved in insulin regulation and
      diabetes. Our integrative methodology identified putative controllers and
      regulators of the metabolic response during SF. We functionally validated our
      findings by demonstrating altered glucose and lipid homeostasis in sleep
      fragmented mice. This is the first study to link sleep fragmentation with
      widespread disruptions in visceral adipose tissue transcriptome, and presents a
      generalizable approach to integrate mRNA-miRNA information for systematic mapping
      of regulatory networks.

PMID- 22629441
TI  - BCL11B regulates epithelial proliferation and asymmetric development of the mouse
      mandibular incisor.
AB  - Mouse incisors grow continuously throughout life with enamel deposition uniquely
      on the outer, or labial, side of the tooth. Asymmetric enamel deposition is due
      to the presence of enamel-secreting ameloblasts exclusively within the labial
      epithelium of the incisor. We have previously shown that mice lacking the
      transcription factor BCL11B/CTIP2 (BCL11B hereafter) exhibit severely disrupted
      ameloblast formation in the developing incisor. We now report that BCL11B is a
      key factor controlling epithelial proliferation and overall developmental
      asymmetry of the mouse incisor: BCL11B is necessary for proliferation of the
      labial epithelium and development of the epithelial stem cell niche, which gives
      rise to ameloblasts; conversely, BCL11B suppresses epithelial proliferation, and
      development of stem cells and ameloblasts on the inner, or lingual, side of the
      incisor. This bidirectional action of BCL11B in the incisor epithelia appears
      responsible for the asymmetry of ameloblast localization in developing incisor.
      Underlying these spatio-specific functions of BCL11B in incisor development is
      the regulation of a large gene network comprised of genes encoding several
      members of the FGF and TGFbeta superfamilies, Sprouty proteins, and Sonic
      hedgehog. Our data integrate BCL11B into these pathways during incisor
      development and reveal the molecular mechanisms that underlie phenotypes of both
      Bcl11b(-/-) and Sprouty mutant mice.

PMID- 22629442
TI  - Evaluation of allele-specific somatic changes of genome-wide association study
      susceptibility alleles in human colorectal cancers.
AB  - BACKGROUND: Tumors frequently exhibit loss of tumor suppressor genes or allelic
      gains of activated oncogenes. A significant proportion of cancer susceptibility
      loci in the mouse show somatic losses or gains consistent with the presence of a
      tumor susceptibility or resistance allele. Thus, allele-specific somatic gains or
      losses at loci may demarcate the presence of resistance or susceptibility
      alleles. The goal of this study was to determine if previously mapped
      susceptibility loci for colorectal cancer show evidence of allele-specific
      somatic events in colon tumors. METHODS: We performed quantitative genotyping of
      16 single nucleotide polymorphisms (SNPs) showing statistically significant
      association with colorectal cancer in published genome-wide association studies
      (GWAS). We genotyped 194 paired normal and colorectal tumor DNA samples and 296
      paired validation samples to investigate these SNPs for allele-specific somatic
      gains and losses. We combined analysis of our data with published data for seven
      of these SNPs. RESULTS: No statistically significant evidence for allele-specific
      somatic selection was observed for the tested polymorphisms in the discovery set.
      The rs6983267 variant, which has shown preferential loss of the non-risk T allele
      and relative gain of the risk G allele in previous studies, favored relative gain
      of the G allele in the combined discovery and validation samples (corrected p
      value = 0.03). When we combined our data with published allele-specific imbalance
      data for this SNP, the G allele of rs6983267 showed statistically significant
      evidence of relative retention (p-value = 2.06*10(-4)). CONCLUSIONS: Our results
      suggest that the majority of variants identified as colon cancer susceptibility
      alleles through GWAS do not exhibit somatic allele-specific imbalance in colon
      tumors. Our data confirm previously published results showing allele-specific
      imbalance for rs6983267. These results indicate that allele-specific imbalance of
      cancer susceptibility alleles may not be a common phenomenon in colon cancer.

PMID- 22629443
TI  - Neural crest cell survival is dependent on Rho kinase and is required for
      development of the mid face in mouse embryos.
AB  - Neural crest cells (NCC) give rise to much of the tissue that forms the
      vertebrate head and face, including cartilage and bone, cranial ganglia and
      teeth. In this study we show that conditional expression of a dominant-negative
      (DN) form of Rho kinase (Rock) in mouse NCC results in severe hypoplasia of the
      frontonasal processes and first pharyngeal arch, ultimately resulting in
      reduction of the maxilla and nasal bones and severe craniofacial clefting
      affecting the nose, palate and lip. These defects resemble frontonasal dysplasia
      in humans. Disruption of the actin cytoskeleton, which leads to abnormalities in
      cell-matrix attachment, is seen in the RockDN;Wnt1-cre mutant embryos. This leads
      to elevated cell death, resulting in NCC deficiency and hypoplastic NCC-derived
      craniofacial structures. Rock is thus essential for survival of NCC that form the
      craniofacial region. We propose that reduced NCC numbers in the frontonasal
      processes and first pharyngeal arch, resulting from exacerbated cell death, may
      be the common mechanism underlying frontonasal dysplasia.

PMID- 22629444
TI  - Mitochondrial structure, function and dynamics are temporally controlled by c
      Myc.
AB  - Although the c-Myc (Myc) oncoprotein controls mitochondrial biogenesis and
      multiple enzymes involved in oxidative phosphorylation (OXPHOS), the coordination
      of these events and the mechanistic underpinnings of their regulation remain
      largely unexplored. We show here that re-expression of Myc in myc-/- fibroblasts
      is accompanied by a gradual accumulation of mitochondrial biomass and by
      increases in membrane polarization and mitochondrial fusion. A correction of
      OXPHOS deficiency is also seen, although structural abnormalities in electron
      transport chain complexes (ETC) are not entirely normalized. Conversely, the down
      regulation of Myc leads to a gradual decrease in mitochondrial mass and a more
      rapid loss of fusion and membrane potential. Increases in the levels of proteins
      specifically involved in mitochondrial fission and fusion support the idea that
      Myc affects mitochondrial mass by influencing both of these processes, albeit
      favoring the latter. The ETC defects that persist following Myc restoration may
      represent metabolic adaptations, as mitochondrial function is re-directed away
      from producing ATP to providing a source of metabolic precursors demanded by the
      transformed cell.

PMID- 22629445
TI  - Inhibition of serine palmitoyl transferase I reduces cardiac ceramide levels and
      increases glycolysis rates following diet-induced insulin resistance.
AB  - OBJECTIVE: Diet-induced obesity (DIO) leads to an accumulation of intra
      myocardial lipid metabolites implicated in causing cardiac insulin resistance and
      contractile dysfunction. One such metabolite is ceramide, and our aim was to
      determine the effects of inhibiting de novo ceramide synthesis on cardiac
      function and insulin stimulated glucose utilization in mice subjected to DIO.
      MATERIALS AND METHODS: C57BL/6 mice were fed a low fat diet or subjected to DIO
      for 12 weeks, and then treated for 4 weeks with either vehicle control or the
      serine palmitoyl transferase I (SPT I) inhibitor, myriocin. In vivo cardiac
      function was assessed via ultrasound echocardiography, while glucose metabolism
      was assessed in isolated working hearts. RESULTS: DIO was not associated with an
      accumulation of intra-myocardial ceramide, but rather, an accumulation of intra
      myocardial DAG (2.63+/-0.41 vs. 4.80+/-0.97 nmol/g dry weight). Nonetheless,
      treatment of DIO mice with myriocin decreased intra-myocardial ceramide levels
      (50.3+/-7.7 vs. 26.9+/-2.7 nmol/g dry weight) and prevented the DIO-associated
      increase in intra-myocardial DAG levels. Interestingly, although DIO impaired
      myocardial glycolysis rates (7789+/-1267 vs. 2671+/-326 nmol/min/g dry weight),
      hearts from myriocin treated DIO mice exhibited an increase in glycolysis rates.
      CONCLUSIONS: Our data reveal that although intra-myocardial ceramide does not
      accumulate following DIO, inhibition of de novo ceramide synthesis nonetheless
      reduces intra-myocardial ceramide levels and prevents the accumulation of intra
      myocardial DAG. These effects improved the DIO-associated impairment of cardiac
      glycolysis rates, suggesting that SPT I inhibition increases cardiac glucose
      utilization.

PMID- 22629446
TI  - Penicillamine increases free copper and enhances oxidative stress in the brain of
      toxic milk mice.
AB  - Wilson disease (WD) is characterized by the accumulation of copper arising from a
      mutation in the ATP7B gene. Penicillamine (PA) makes 10-50% of the patients with
      neurologic symptoms neurologically worse at the early stage of administration.
      The aim of this study was to determine how the copper metabolism changes and
      whether the change impairs the brain of toxic milk (tx) mice, an animal model of
      WD, during the PA administration. The free copper and protein-bound copper
      concentrations in the serum, cortex and basal ganglia of tx mice with PA
      administration for 3 days, 10 days and 14 days, respectively, were investigated.
      The expression of copper transporters, ATP7A and CTR1,was analyzed by real-time
      quantitative PCR, immunofluorescence and Western blot. Then SOD, MDA and GSH/GSSG
      were detected to determine whether the oxidative stress changed correspondingly.
      The results revealed the elevated free copper concentrations in the serum and
      brain, and declined protein-bound copper concentrations in the brain of tx mice
      during PA administration. Meanwhile, transiently increased expression of ATP7A
      and CTR1 was observed generally in the brain parenchyma by immunofluorescence,
      real-time quantitative PCR and Western blot. Additionally, ATP7A and CTR1 were
      observed to locate mainly at Golgi apparatus and cellular membrane respectively.
      Intense staining of ATP7A in the choroid plexus was found in tx mice on the 3rd
      and 10th day of PA treatment, but rare staining of ATP7A and CTR1 in the blood
      brain barrier (BBB). Decreased GSH/GSSG and increased MDA concentrations were
      also viewed in the cortex and basal ganglia. Our results suggested the elevated
      free copper concentrations in the brain might lead to the enhanced oxidative
      stress during PA administration. The increased free copper in the brain might
      come from the copper mobilized from brain parenchyma cells but not from the serum
      according to the ATP7A and CTR1 expression analysis.

PMID- 22629447
TI  - Comparison of sexual behavior and HIV risk between two HIV-1 serodiscordant
      couple cohorts: the CHAVI 002 study.
AB  - BACKGROUND: The CHAVI002 study was designed to characterize immune responses,
      particularly HIV-specific T-cell responses, amongst 2 cohorts of HIV-exposed
      seronegative (HESN) individuals. The absence of a clear definition of HESNs has
      impaired comparison of research within and between such cohorts. This report
      describes two distinct HESN cohorts and attempts to quantify HIV exposure using a
      'HIV risk index' (RI) model. METHODS: HIV serodiscordant couples (UK; 24, Uganda;
      72) and HIV unexposed seronegative (HUSN) controls (UK; 14, Uganda; 26 couples, 3
      individuals) completed sexual behavior questionnaires every 3 months over a 9
      month period. The two cohorts were heterogeneous, with most HESNs in the UK men
      who have sex with men (MSM), while all HESNs in Uganda were in heterosexual
      relationships. Concordance of responses between partners was determined. Each
      participant's sexual behavior score (SBS) was estimated based on the number and
      type of unprotected sex acts carried out in defined time periods. Independent HIV
      acquisition risk factors (partner plasma viral load, STIs, male circumcision,
      pregnancy) were integrated with the SBS, generating a RI for each HESN. RESULTS:
      96 HIV serodiscordant couples completed 929 SBQs. SBSs remained relatively stable
      amongst the UK cohort, whilst decreasing from Visit 1 to 2 in the Ugandan cohort.
      Compared to the Ugandan cohort, SBSs and RIs in the UK cohort were lower at visit
      1, and generally higher at later visits. Differences between the cohorts, with
      lower rates of ART use in Uganda and higher risk per-act sex in the UK, had major
      impacts on the SBSs and RIs of each cohort. There was one HIV transmission event
      in the UK cohort. CONCLUSIONS: Employment of a risk quantification model
      facilitated quantification and comparison of HIV acquisition risk across two
      disparate HIV serodiscordant couple cohorts.

PMID- 22629449
TI  - Tinnitus severity is reduced with reduction of depressive mood--a prospective
      population study in Sweden.
AB  - Tinnitus, the perception of sound without external source, is a highly prevalent
      public health problem with about 8% of the population having frequently occurring
      tinnitus, and about 1-2% experiencing significant distress from it. Population
      studies, as well as studies on self-selected samples, have reported poor
      psychological well-being in individuals with tinnitus. However, no study has
      examined the long-term co-variation between mood and tinnitus prevalence or
      tinnitus severity. In this study, the relationship between depression and
      tinnitus prevalence and severity over a 2-year period was examined in a
      representative sample of the general Swedish working population. Results show
      that a decrease in depression is associated with a decrease in tinnitus
      prevalence, and even more markedly with tinnitus severity. Hearing loss was a
      more potent predictor than depression for tinnitus prevalence, but was a weaker
      predictor than depression for tinnitus severity. In addition, there were sex
      differences for tinnitus prevalence, but not for tinnitus severity. This study
      shows a direct and long-term association between tinnitus severity and
      depression.

PMID- 22629448
TI  - Procyanidin B3 prevents articular cartilage degeneration and heterotopic
      cartilage formation in a mouse surgical osteoarthritis model.
AB  - Osteoarthritis (OA) is a common disease in the elderly due to an imbalance in
      cartilage degradation and synthesis. Heterotopic ossification (HO) occurs when
      ectopic masses of endochondral bone form within the soft tissues around the
      joints and is triggered by inflammation of the soft tissues. Procyanidin B3 (B3)
      is a procyanidin dimer that is widely studied due to its high abundance in the
      human diet and antioxidant activity. Here, we evaluated the role of B3 isolated
      from grape seeds in the maintenance of chondrocytes in vitro and in vivo. We
      observed that B3 inhibited H(2)O(2)-induced apoptosis in primary chondrocytes,
      suppressed H(2)O(2)- or IL-1beta-induced nitric oxide synthase (iNOS) production,
      and prevented IL-1beta-induced suppression of chondrocyte differentiation marker
      gene expression in primary chondrocytes. Moreover, B3 treatment enhanced the
      early differentiation of ATDC5 cells. To examine whether B3 prevents cartilage
      destruction in vivo, OA was surgically induced in C57BL/6J mice followed by oral
      administration of B3 or vehicle control. Daily oral B3 administration protected
      articular cartilage from OA and prevented chondrocyte apoptosis in surgically
      induced OA joints. Furthermore, B3 administration prevented heterotopic cartilage
      formation near the surgical region. iNOS protein expression was enhanced in the
      synovial tissues and the pseudocapsule around the surgical region in OA mice fed
      a control diet, but was reduced in mice that received B3. Together, these data
      indicated that in the OA model, B3 prevented OA progression and heterotopic
      cartilage formation, at least in a part through the suppression of iNOS. These
      results support the potential therapeutic benefits of B3 for treatment of human
      OA and heterotopic ossification.

PMID- 22629450
TI  - The role of attention in ambiguous reversals of structure-from-motion.
AB  - Multiple dots moving independently back and forth on a flat screen induce a
      compelling illusion of a sphere rotating in depth (structure-from-motion). If all
      dots simultaneously reverse their direction of motion, two perceptual outcomes
      are possible: either the illusory rotation reverses as well (and the illusory
      depth of each dot is maintained), or the illusory rotation is maintained (but the
      illusory depth of each dot reverses). We investigated the role of attention in
      these ambiguous reversals. Greater availability of attention--as manipulated with
      a concurrent task or inferred from eye movement statistics--shifted the balance
      in favor of reversing illusory rotation (rather than depth). On the other hand,
      volitional control over illusory reversals was limited and did not depend on
      tracking individual dots during the direction reversal. Finally, display
      properties strongly influenced ambiguous reversals. Any asymmetries between
      'front' and 'back' surfaces--created either on purpose by coloring or
      accidentally by random dot placement--also shifted the balance in favor of
      reversing illusory rotation (rather than depth). We conclude that the outcome of
      ambiguous reversals depends on attention, specifically on attention to the
      illusory sphere and its surface irregularities, but not on attentive tracking of
      individual surface dots.

PMID- 22629451
TI  - Predicting inter-species cross-talk in two-component signalling systems.
AB  - Phosphosignalling pathways are an attractive option for the synthetic biologist
      looking for a wide repertoire of modular components from which to build. We
      demonstrate that two-component systems can be used in synthetic biology. However,
      their potential is limited by the fact that host cells contain many of their own
      phosphosignalling pathways and these may interact with, and cross-talk to, the
      introduced synthetic components. In this paper we also demonstrate a simple
      bioinformatic tool that can help predict whether interspecies cross-talk between
      introduced and native two-component signalling pathways will occur and show both
      in vitro and in vivo that the predicted interactions do take place. The ability
      to predict potential cross-talk prior to designing and constructing novel
      pathways or choosing a host organism is essential for the promise that
      phosphosignalling components hold for synthetic biology to be realised.

PMID- 22629452
TI  - Monsoon versus uplift in southwestern China--Late Pliocene climate in Yuanmou
      Basin, Yunnan.
AB  - Yuanmou Basin of Yunnan, SW China, is a famous locality with hominids, hominoids,
      mammals and plant fossils. Based on the published megaflora and palynoflora data
      from Yuanmou Basin, the climate of Late Pliocene is reconstructed using the
      Coexistence Approach. The results indicate a warm and humid subtropical climate
      with a mean annual temperature of ca. 16-17 degrees C and a mean annual
      precipitation of ca. 1500-1600 mm in the Late Pliocene rather than a dry, hot
      climate today, which may be due to the local tectonic change and gradual
      intensification of India monsoon. The comparison of Late Pliocene climate in
      Eryuan, Yangyi, Longling, and Yuanmou Basin of Yunnan Province suggests that the
      mean annual temperatures generally show a latitudinal gradient and fit well with
      their geographic position, while the mean annual precipitations seem to be
      related to the different geometries of the valleys under the same monsoon system.

PMID- 22629453
TI  - AAV2-mediated subretinal gene transfer of mIL-27p28 attenuates experimental
      autoimmune uveoretinitis in mice.
AB  - BACKGROUND: Advances in gene transfer techniques have provided long-term, safe
      and stable transduction of retinal cells following subretinal injection with
      adeno-associated viral (AAV) vectors. In this study we investigated whether
      subretinal injection of AAV2-murine IL-27p28 vector was effective in inhibiting
      experimental autoimmune uveoretinitis (EAU) induced in B10RIII mice.
      METHODOLOGY/PRINCIPAL FINDINGS: An AAV2 vector encoding the murine IL-27p28 gene
      (rAAV2-CMV-mIL-27p28) was prepared and subretinally injected into B10RIII mice
      (4.35*10(8) vector genome (v.g.)). AAV2 vector mediating green fluorescent
      protein (rAAV2-CMV-GFP) served as a control (5*10(8) v.g.). The concentration of
      mIL-27p28 in homogenized eyes and serum was assayed by enzyme linked
      immunosorbent assay (ELISA) after subretinal injection. Human IRBP(161-180)
      peptide and Complete Freund's Adjuvant were injected into mice receiving either
      the rAAV2-CMV-mIL-27p28 or rAAV2-CMV-GFP vector. EAU was evaluated clinically and
      pathologically. The level of IL-17 and IL-10 in homogenized eyes was measured on
      day 12 and day 21 following immunization. Delayed type hypersensitivity (DTH) and
      IRBP(161-180)-specific proliferation of lymphocytes from the spleen and lymph
      nodes were assayed to examine the influence of the subretinal delivery of rAAV2
      CMV-mIL-27p28 on the systemic immune response. IL-27p28 was detectable by ELISA
      within the eyes from two weeks following subretinal injection of the rAAV2-CMV
      mIL-27p28 vector and showed a sustained high expression from day 14 to 9 months
      with a highest expression at 5 months. Subretinal injection of the vector
      significantly attenuated the severity of EAU disease clinically and
      pathologically in association with a significantly decreased IL-17 expression and
      an increased IL-10 expression. The IL-27p28 vector did not affect the systemic
      immune response, as determined by DTH and IRBP(161-180)-specific lymphocyte
      proliferation. CONCLUSIONS/SIGNIFICANCE: A high and stable expression of IL-27p28
      was observed for at least 9 months following subretinal delivery of rAAV2-CMV-mIL
      27p28. The amelioration of EAU disease severity was associated with a decreased
      IL-17 expression and an increased IL-10 expression.

PMID- 22629454
TI  - Divergent genomic and epigenomic landscapes of lung cancer subtypes underscore
      the selection of different oncogenic pathways during tumor development.
AB  - For therapeutic purposes, non-small cell lung cancer (NSCLC) has traditionally
      been regarded as a single disease. However, recent evidence suggest that the two
      major subtypes of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SqCC)
      respond differently to both molecular targeted and new generation chemotherapies.
      Therefore, identifying the molecular differences between these tumor types may
      impact novel treatment strategy. We performed the first large-scale analysis of
      261 primary NSCLC tumors (169 AC and 92 SqCC), integrating genome-wide DNA copy
      number, methylation and gene expression profiles to identify subtype-specific
      molecular alterations relevant to new agent design and choice of therapy.
      Comparison of AC and SqCC genomic and epigenomic landscapes revealed 778 altered
      genes with corresponding expression changes that are selected during tumor
      development in a subtype-specific manner. Analysis of >200 additional NSCLCs
      confirmed that these genes are responsible for driving the differential
      development and resulting phenotypes of AC and SqCC. Importantly, we identified
      key oncogenic pathways disrupted in each subtype that likely serve as the basis
      for their differential tumor biology and clinical outcomes. Downregulation of
      HNF4alpha target genes was the most common pathway specific to AC, while SqCC
      demonstrated disruption of numerous histone modifying enzymes as well as the
      transcription factor E2F1. In silico screening of candidate therapeutic compounds
      using subtype-specific pathway components identified HDAC and PI3K inhibitors as
      potential treatments tailored to lung SqCC. Together, our findings suggest that
      AC and SqCC develop through distinct pathogenetic pathways that have significant
      implication in our approach to the clinical management of NSCLC.

PMID- 22629456
TI  - Increase of carbapenem-resistant Acinetobacter baumannii infection in acute care
      hospitals in Taiwan: association with hospital antimicrobial usage.
AB  - OBJECTIVE: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as an
      important pathogen causing healthcare-associated infections (HAIs) in Taiwan. The
      present study is aimed to investigate the epidemiology of HAIs caused by CRAB and
      the association of CRAB infection and hospital usage of different antimicrobials.
      METHODS: Two nationwide databases in the period 2003 to 2008, the Taiwan
      Nosocomial Infection Surveillance System and National Health Insurance claim
      data, were used for analysis. A total of 13,811 healthcare-associated A.
      baumannii infections and antimicrobial usage data from 121 hospitals were
      analyzed. RESULTS: There was a significant increase in the proportion of number
      of HAIs caused by CRAB over that by all A. baumannii (CRABpAB), from 14% in 2003
      to 46% in 2008 (P<0.0001). The greatest increase was in central Taiwan, from 4%
      in 2003 to 62% in 2008 (P<0.0001). Use of anti-pseudomonal carbapenems, but not
      other classes of antibiotics, was significantly correlated with the increase of
      CRABpAB (r = 0.86, P<0.0001). CONCLUSIONS: We suggested that dedicated use of
      anti-pseudomonal carbapenems would be an important intervention to control the
      increase of CRABpAB.

PMID- 22629455
TI  - FADS1 FADS2 gene cluster, PUFA intake and blood lipids in children: results from
      the GINIplus and LISAplus studies.
AB  - BACKGROUND: Elevated cholesterol levels in children can be a risk factor for
      cardiovascular diseases in later life. In adults, it has been shown that blood
      lipid levels are strongly influenced by polymorphisms in the fatty acid
      desaturase (FADS) gene cluster in addition to nutritional and other exogenous and
      endogenous determinants. Our aim was to investigate whether lipid levels are
      determined by the FADS genotype already in children and whether this association
      interacts with dietary intake of n-3 fatty acids. METHODS: The analysis was based
      on data of 2006 children from two German prospective birth cohort studies. Total
      cholesterol, HDL, LDL and triglycerides were measured at 10 years of age. Six
      single nucleotide polymorphisms (SNPs) of the FADS gene cluster were genotyped.
      Dietary n-3 fatty acid intake was assessed by food frequency questionnaire.
      Linear regression modeling was used to assess the association between lipid
      levels, n-3 fatty acid intake and FADS genotype. RESULTS: Individuals carrying
      the homozygous minor allele had lower levels of total cholesterol [means ratio
      (MR) ranging from 0.96 (p = 0.0093) to 0.98 (p = 0.2949), depending on SNPs] and
      LDL [MR between 0.94 (p = 0.0179) and 0.97 (p = 0.2963)] compared to homozygous
      major allele carriers. Carriers of the heterozygous allele showed lower HDL
      levels [beta between -0.04 (p = 0.0074) to -0.01 (p = 0.3318)] and higher
      triglyceride levels [MR ranging from 1.06 (p = 0.0065) to 1.07 (p = 0.0028)]
      compared to homozygous major allele carriers. A higher n-3 PUFA intake was
      associated with higher concentrations of total cholesterol, LDL, HDL and lower
      triglyceride levels, but these associations did not interact with the FADS1 FADS2
      genotype. CONCLUSION: Total cholesterol, HDL, LDL and triglyceride concentrations
      may be influenced by the FADS1 FADS2 genotype already in 10 year old children.
      Genetically determined blood lipid levels during childhood might differentially
      predispose individuals to the development of cardiovascular diseases later in
      life.

PMID- 22629457
TI  - CCL18 in a multiplex urine-based assay for the detection of bladder cancer.
AB  - The early detection of bladder cancer (BCa) is pivotal for successful patient
      treatment and management. Through genomic and proteomic studies, we have
      identified a number of bladder cancer-associated biomarkers that have potential
      clinical utility. In a case-control study, we examined voided urines from 127
      subjects: 64 tumor-bearing subjects and 63 controls. The urine concentrations of
      the following proteins were assessed by enzyme-linked immunosorbent assay
      (ELISA); C-C motif chemokine 18 (CCL18), Plasminogen Activator Inhibitor 1 (PAI
      1) and CD44. Data were compared to a commercial ELISA-based BCa detection assay
      (BTA-Trak(c)) and voided urinary cytology. We used analysis of the area under the
      curve of receiver operating characteristic curves to compare the ability of
      CCL18, PAI-1, CD44, and BTA to detect BCa in voided urine samples. Urinary
      concentrations of CCL18, PAI-1, and BTA were significantly elevated in subjects
      with BCa. CCL18 was the most accurate biomarker (AUC; 0.919; 95% confidence
      interval [CI], 0.8704-0.9674). Multivariate regression analysis highlighted CCL18
      (OR; 18.31; 95% CI, 4.95-67.70, p<0.0001) and BTA (OR; 6.43; 95% CI, 1.86-22.21,
      p = 0.0033) as independent predictors of BCa in voided urine samples. The
      combination of CCL18, PAI-1 and CD44 improved the area under the curve to 0.938.
      Preliminary results indicate that CCL18 was a highly accurate biomarker for BCa
      detection in this cohort. Monitoring CCL18 in voided urine samples has the
      potential to improve non-invasive tests for BCa diagnosis. Furthermore using the
      combination of CCL18, PAI-1 and CD44 may make the model more robust to errors to
      detect BCa over the individual biomarkers or BTA.

PMID- 22629458
TI  - Age-related changes in the daily rhythm of photoreceptor functioning and
      circuitry in a melatonin-proficient mouse strain.
AB  - Retinal melatonin is involved in the modulation of many important retinal
      functions. Our previous studies have shown that the viability of photoreceptors
      and ganglion cells is reduced during aging in mice that lack melatonin receptor
      type 1. This demonstrates that melatonin signaling is important for the survival
      of retinal neurons. In the present study, we investigate the effects of aging on
      photoreceptor physiology and retinal organization in CH3-f+/+ mice, a melatonin
      proficient mouse strain. Our data indicate that the amplitude of the a and b
      waves of the scotopic and photopic electroretinogram decreases with age.
      Moreover, the daily rhythm in the amplitude of the a- and b-waves is lost during
      the aging process. Similarly, the scotopic threshold response is significantly
      affected by aging, but only when it is measured during the night. Interestingly,
      the changes observed in the ERGs are not paralleled by relevant changes in
      retinal morphological features, and administration of exogenous melatonin does
      not affect the ERGs in C3H-f(+/+) at 12 months of age. This suggests that the
      responsiveness of the photoreceptors to exogenous melatonin is reduced during
      aging.

PMID- 22629459
TI  - Identification of Nicotiana tabacum linkage group corresponding to the Q
      chromosome gene(s) involved in hybrid lethality.
AB  - BACKGROUND: A linkage map consisting of 24 linkage groups has been constructed
      using simple sequence repeat (SSR) markers in Nicotiana tabacum. However,
      chromosomal assignments of all linkage groups have not yet been made. The Q
      chromosome in N. tabacum encodes a gene or genes triggering hybrid lethality, a
      phenomenon that causes death of hybrids derived from some crosses.
      METHODOLOGY/PRINCIPAL FINDINGS: We identified a linkage group corresponding to
      the Q chromosome using an interspecific cross between an N. tabacum monosomic
      line lacking the Q chromosome and N. africana. N. ingulba yielded inviable
      hybrids after crossing with N. tabacum. SSR markers on the identified linkage
      group were used to analyze hybrid lethality in this cross. The results implied
      that one or more genes on the Q chromosome are responsible for hybrid lethality
      in this cross. Furthermore, the gene(s) responsible for hybrid lethality in the
      cross N. tabacum * N. africana appear to be on the region of the Q chromosome to
      which SSR markers PT30342 and PT30365 map. CONCLUSIONS/SIGNIFICANCE: Linkage
      group 11 corresponded to the Q chromosome. We propose a new method to correlate
      linkage groups with chromosomes in N. tabacum.

PMID- 22629460
TI  - Hepatic fat accumulation is modulated by the interaction between the rs738409
      variant in the PNPLA3 gene and the dietary omega6/omega3 PUFA intake.
AB  - BACKGROUND: A single nucleotide polymorphism (SNP), the rs738409, in the patatin
      like phospholipase 3 gene (PNPLA3) has been recently associated with increased
      hepatic steatosis and ALT levels in adults and children. Given the potential role
      of PNPLA3 in fatty liver development, we aimed to explore whether the influence
      of PNPLA3 genotype on hepatic fat in obese youth might be modulated by dietary
      factors such as essential omega polyunsaturated fatty acids (PUFA) intake.
      MATERIALS AND METHODS: We studied 127 children and adolescents (56 boys, 71
      girls; 58 Caucasians; 30 African Americans and 39 Hispanics; mean age 14.7+/-3.3;
      mean BMI 30.7+/-7.2). The dietary composition was assessed by the Nutrition Data
      System for Research (NDS-R version 2011). The patients underwent a MRI study to
      assess the liver fat content (HFF%), ALT measurement and the genotyping of the
      rs738409 SNP by automatic sequencing. RESULTS: As previously observed, HFF% and
      ALT levels varied according to the genotype in each ethnicity. ALT levels and
      HFF% were significantly influenced by the interaction between genotype and omega
      6/omega-3 PUFA ratio (n-6/n-3), p = 0.003 and p = 0.002, respectively. HFF% and
      ALT levels were, in fact, related to the n-6/n-3 consumption only in subjects
      homozygote for the G allele of the rs738409 (r2 = 0.45, p =  0.001 and r2 = 0.40,
      p = 0.006, respectively). CONCLUSIONS: These findings suggest that the
      association of a high dietary n-6/n-3 PUFA with fatty liver and liver damage in
      obese youths may be driven by a predisposing genotype.

PMID- 22629461
TI  - Dispersal routes and habitat utilization of juvenile Atlantic bluefin tuna,
      Thunnus thynnus, tracked with mini PSAT and archival tags.
AB  - Between 2005 and 2009, we deployed 58 miniature pop-up satellite archival tags
      (PSAT) and 132 implanted archival tags on juvenile Atlantic bluefin tuna (age 2
      5) in the northwest Atlantic Ocean. Data returned from these efforts (n = 26
      PSATs, 1 archival tag) revealed their dispersal routes, horizontal and vertical
      movements and habitat utilization. All of the tagged bluefin tuna remained in the
      northwest Atlantic for the duration observed, and in summer months exhibited core
      use of coastal seas extending from Maryland to Cape Cod, MA, (USA) out to the
      shelf break. Their winter distributions were more spatially disaggregated,
      ranging south to the South Atlantic Bight, northern Bahamas and Gulf Stream.
      Vertical habitat patterns showed that juvenile bluefin tuna mainly occupied
      shallow depths (mean= 5-12 m, sd = 15-23.7 m) and relatively warm water masses in
      summer (mean= 17.9-20.9 degrees C, sd= 4.2-2.6 degrees C) and had deeper and more
      variable depth patterns in winter (mean= 41-58 m, sd= 48.9-62.2 m). Our tagging
      results reveal annual dispersal patterns, behavior and oceanographic associations
      of juvenile Atlantic bluefin tuna that were only surmised in earlier studies.
      Fishery independent profiling from electronic tagging also provide spatially and
      temporally explicit information for evaluating dispersals rates, population
      structure and fisheries catch patterns.

PMID- 22629462
TI  - D1 dopamine receptor signaling is modulated by the R7 RGS protein EAT-16 and the
      R7 binding protein RSBP-1 in Caenoerhabditis elegans motor neurons.
AB  - Dopamine signaling modulates voluntary movement and reward-driven behaviors by
      acting through G protein-coupled receptors in striatal neurons, and defects in
      dopamine signaling underlie Parkinson's disease and drug addiction. Despite the
      importance of understanding how dopamine modifies the activity of striatal
      neurons to control basal ganglia output, the molecular mechanisms that control
      dopamine signaling remain largely unclear. Dopamine signaling also controls
      locomotion behavior in Caenorhabditis elegans. To better understand how dopamine
      acts in the brain we performed a large-scale dsRNA interference screen in C.
      elegans for genes required for endogenous dopamine signaling and identified six
      genes (eat-16, rsbp-1, unc-43, flp-1, grk-1, and cat-1) required for dopamine
      mediated behavior. We then used a combination of mutant analysis and cell
      specific transgenic rescue experiments to investigate the functional interaction
      between the proteins encoded by two of these genes, eat-16 and rsbp-1, within
      single cell types and to examine their role in the modulation of dopamine
      receptor signaling. We found that EAT-16 and RSBP-1 act together to modulate
      dopamine signaling and that while they are coexpressed with both D1-like and D2
      like dopamine receptors, they do not modulate D2 receptor signaling. Instead, EAT
      16 and RSBP-1 act together to selectively inhibit D1 dopamine receptor signaling
      in cholinergic motor neurons to modulate locomotion behavior.

PMID- 22629463
TI  - Therapeutic dosing of acenocoumarol: proposal of a population specific
      pharmacogenetic dosing algorithm and its validation in north Indians.
AB  - OBJECTIVES: To develop a population specific pharmacogenetic acenocoumarol dosing
      algorithm for north Indian patients and show its efficiency in dosage prediction.
      METHODS: Multiple and linear stepwise regression analyses were used to include
      age, sex, height, weight, body surface area, smoking status, VKORC1 -1639 G>A,
      CYP4F2 1347 G>A, CYP2C9*2,*3 and GGCX 12970 C>G polymorphisms as variables to
      generate dosing algorithms. The new dosing models were compared with already
      reported algorithms and also with the clinical data for various performance
      measures. Odds ratios for association of genotypes with drug sensitive and
      resistant groups were calculated. RESULTS: The pharmacogenetic dosing algorithm
      generated by multiple regression analysis explains 41.4% (p-value <0.001) of
      dosage variation. Validation of the new algorithm showed its predictive ability
      to be better than the already established algorithms based on similar variables.
      Its validity in our population is reflected by increased sensitivity,
      specificity, accuracy and decreased rates of over- and under-estimation in
      comparison to clinical data. The VKORC1-1639 G>A polymorphism was found to be
      strongly associated with acenocoumarol sensitivity according to recessive model.
      CONCLUSIONS: We have proposed an efficient north India specific pharmacogenetic
      acenocoumarol dosing algorithm which might become a baseline for personalised
      medicine approach for treatment of patients in future.

PMID- 22629464
TI  - Early Ahmed glaucoma valve implantation after penetrating keratoplasty leads to
      better outcomes in an Asian population with preexisting glaucoma.
AB  - BACKGROUND: To evaluate the efficacy of Ahmed Glaucoma Valve (AGV) surgery and
      the optimal interval between penetrating keratoplasty (PKP) and AGV implantation
      in a population of Asian patients with preexisting glaucoma who underwent PKP.
      METHODOLOGY/PRINCIPAL FINDINGS: In total, 45 eyes of 45 patients were included in
      this retrospective chart review. The final intraocular pressures (IOPs), graft
      survival rate, and changes in visual acuity were assessed to evaluate the
      outcomes of AGV implantations in eyes in which AGV implantation occurred within 1
      month of post-PKP IOP elevation (Group 1) and in eyes in which AGV implantation
      took place more than 1 month after the post-PKP IOP evaluation (Group 2). Factors
      that were associated with graft failure were analyzed, and the overall patterns
      of complications were reviewed. By their final follow-up visits, 58% of the
      patients had been successfully treated for glaucoma. After the operation, there
      were no statistically significant differences between the groups with respect to
      graft survival (p = 0.98), but significant differences for IOP control (p =
      0.049) and the maintenance of visual acuity (VA) (p<0.05) were observed. One year
      after surgery, the success rates of IOP control in Group 1 and Group 2 were 80%
      and 46.7%, respectively, and these rates fell to 70% and 37.3%, respectively, by
      2 years. Factors that were associated with a high risk of AGV failure were a
      diagnosis of preexisting angle-closure glaucoma, a history of previous PKP, and a
      preoperative IOP that was >21 mm Hg. The most common surgical complication, aside
      from graft failure, was hyphema. CONCLUSIONS/SIGNIFICANCE: Early AGV implantation
      results in a higher probability of AGV survival and a better VA outcome without
      increasing the risk of corneal graft failure as a result of post-PKP glaucoma
      drainage tube implantation.

PMID- 22629466
TI  - Bactericidal action of photogenerated singlet oxygen from photosensitizers used
      in plaque disclosing agents.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been suggested as an efficient
      clinical approach for the treatment of dental plaque in the field of dental care.
      In PDT, once the photosensitizer is irradiated with light of a specific
      wavelength, it transfers the excitation energy to molecular oxygen, which gives
      rise to singlet oxygen. METHODOLOGY/PRINCIPAL FINDINGS: Since plaque disclosing
      agents usually contain photosensitizers such as rose bengal, erythrosine, and
      phloxine, they could be used for PTD upon photoactivation. The aim of the present
      study is to compare the ability of these three photosensitizers to produce
      singlet oxygen in relation to their bactericidal activity. The generation rates
      of singlet oxygen determined by applying an electron spin resonance technique
      were in the order phloxine > erythrosine ? rose bengal. On the other hand, rose
      bengal showed the highest bactericidal activity against Streptococcus mutans, a
      major causative pathogen of caries, followed by erythrosine and phloxine, both of
      which showed activity similar to each other. One of the reasons for the
      discrepancy between the singlet oxygen generating ability and bactericidal
      activity was the incorporation efficiency of the photosensitizers into the
      bacterial cells. The incorporation rate of rose bengal was the highest among the
      three photosensitizers examined in the present study, likely leading to the
      highest bactericidal activity. Meanwhile, the addition of L-histidine, a singlet
      oxygen quencher, cancelled the bactericidal activity of any of the three
      photoactivated photosensitizers, proving that singlet oxygen was responsible for
      the bactericidal action. CONCLUSIONS: It is strongly suggested that rose bengal
      is a suitable photosensitizer for the plaque disclosing agents as compared to the
      other two photosensitizers, phloxine and erythrosine, when used for PDT.

PMID- 22629465
TI  - Neuropeptide Y2 receptor (NPY2R) expression in saliva predicts feeding immaturity
      in the premature neonate.
AB  - BACKGROUND: The current practice in newborn medicine is to subjectively assess
      when a premature infant is ready to feed by mouth. When the assessment is
      inaccurate, the resulting feeding morbidities may be significant, resulting in
      long-term health consequences and millions of health care dollars annually. We
      hypothesized that the developmental maturation of hypothalamic regulation of
      feeding behavior is a predictor of successful oral feeding in the premature
      infant. To test this hypothesis, we analyzed the gene expression of neuropeptide
      Y2 receptor (NPY2R), a known hypothalamic regulator of feeding behavior, in
      neonatal saliva to determine its role as a biomarker in predicting oral feeding
      success in the neonate. METHODOLOGY/PRINCIPAL FINDINGS: Salivary samples (n =
      116), were prospectively collected from 63 preterm and 13 term neonates (post
      conceptual age (PCA) 26 4/7 to 41 4/7 weeks) from five predefined feeding stages.
      Expression of NPY2R in neonatal saliva was determined by multiplex RT-qPCR
      amplification. Expression results were retrospectively correlated with feeding
      status at time of sample collection. Statistical analysis revealed that
      expression of NPY2R had a 95% positive predictive value for feeding immaturity.
      NPY2R expression statistically significantly decreased with advancing PCA
      (Wilcoxon test p value<0.01), and was associated with feeding status (chi square
      p value  =  0.013). CONCLUSIONS/SIGNIFICANCE: Developmental maturation of
      hypothalamic regulation of feeding behavior is an essential component of oral
      feeding success in the newborn. NPY2R expression in neonatal saliva is predictive
      of an immature feeding pattern. It is a clinically relevant biomarker that may be
      monitored in saliva to improve clinical care and reduce significant feeding
      associated morbidities that affect the premature neonate.

PMID- 22629467
TI  - Contrast dependence of smooth pursuit eye movements following a saccade to
      superimposed targets.
AB  - Dorsal stream areas provide motion information used by the oculomotor system to
      generate pursuit eye movements. Neurons in these areas saturate at low levels of
      luminance contrast. We therefore hypothesized that during the early phase of
      pursuit, eye velocity would exhibit an oculomotor gain function that saturates at
      low luminance contrast. To test this, we recorded eye movements in two macaques
      trained to saccade to an aperture in which a pattern of dots moved left or right.
      Shortly after the end of the saccade, the eyes followed the direction of motion
      with an oculomotor gain that increased with contrast before saturating. The
      addition of a second pattern of dots, moving in the opposite direction and
      superimposed on the first, resulted in a rightward shift of the contrast
      dependent oculomotor gain function. The magnitude of this shift increased with
      the contrast of the second pattern of dots. Motion was nulled when the two
      patterns were equal in contrast. Next, we varied contrast over time. Contrast
      differences that disappeared before saccade onset biased post-saccadic eye
      movements at short latency. Changes in contrast occurring during or after saccade
      termination did not influence eye movements for approximately 150 ms. Earlier
      studies found that eye movements can be explained by a vector average computation
      when both targets are equal in contrast. We suggest that this averaging
      computation may reflect a special case of divisive normalization, yielding
      saturating contrast response functions that shift to the right with opposed
      motion, averaging motions when targets are equated in contrast.

PMID- 22629468
TI  - Muscle fiber type-dependent differences in the regulation of protein synthesis.
AB  - This study examined fiber type-dependent differences in the regulation of protein
      synthesis in individual muscle fibers found within the same whole muscle.
      Specifically, the in vivo SUrface SEnsing of Translation (SUnSET) methodology was
      used to measure protein synthesis in type 1, 2A, 2X and 2B fibers of the mouse
      plantaris muscle, in response to food deprivation (FD), and mechanical overload
      induced by synergist ablation (SA). The results show that 48 h of FD induced a
      greater decrease in protein synthesis in type 2X and 2B fibers compared to type 1
      and 2A fibers. Type 2X and 2B fibers also had the largest FD-induced decrease in
      total S6 protein and Ser(240/244) S6 phosphorylation, respectively. Moreover,
      only type 2X and 2B fibers displayed a FD-induced decrease in cross-sectional
      area (CSA). Ten days of SA also induced fiber type-dependent responses, with type
      2B fibers having the smallest SA-induced increases in protein synthesis, CSA and
      Ser(240/244) S6 phosphorylation, but the largest increase in total S6 protein.
      Embryonic myosin heavy chain (MHC(Emb)) positive fibers were also found in SA
      muscles and the protein synthesis rates, levels of S6 Ser(240/244)
      phosphorylation, and total S6 protein content, were 3.6-, 6.1- and 2.9-fold
      greater than that found in fibers from control muscles, respectively. Overall,
      these results reveal differential responses in the regulation of protein
      synthesis and fiber size between fiber types found within the same whole muscle.
      Moreover, these findings demonstrate that changes found at the whole muscle level
      do not necessarily reflect changes in individual fiber types.

PMID- 22629469
TI  - Weekly intra-amniotic IGF-1 treatment increases growth of growth-restricted ovine
      fetuses and up-regulates placental amino acid transporters.
AB  - Frequent treatment of the growth-restricted (IUGR) ovine fetus with intra
      amniotic IGF-1 increases fetal growth. We aimed to determine whether increased
      growth was maintained with an extended dosing interval and to examine possible
      mechanisms. Pregnant ewes were allocated to three groups: Control, and two IUGR
      groups (induced by placental embolization) treated with weekly intra-amniotic
      injections of either saline (IUGR) or 360 ug IGF-1 (IGF1). IUGR fetuses were
      hypoxic, hyperuremic, hypoglycemic, and grew more slowly than controls. Placental
      glucose uptake and SLC2A1 (GLUT2) mRNA levels decreased in IUGR fetuses, but
      SLC2A3 (GLUT3) and SLC2A4 (GLUT4) levels were unaffected. IGF-1 treatment
      increased fetal growth rate, did not alter uterine blood flow or placental
      glucose uptake, and increased placental SLC2A1 and SLC2A4 (but not SLC2A3) mRNA
      levels compared with saline-treated IUGR animals. Following IGF-1 treatment,
      placental mRNA levels of isoforms of the system A, y(+), and L amino acid
      transporters increased 1.3 to 5.0 fold, while the ratio of phosphorylated-mTOR to
      total mTOR also tended to increase. Weekly intra-amniotic IGF-1 treatment
      provides a promising avenue for intra-uterine treatment of IUGR babies, and may
      act via increased fetal substrate supply, up-regulating placental transporters
      for neutral, cationic, and branched-chain amino acids, possibly via increased
      activation of the mTOR pathway.

PMID- 22629470
TI  - Spatial distribution of the pathways of cholesterol homeostasis in human retina.
AB  - BACKGROUND: The retina is a light-sensitive tissue lining the inner surface of
      the eye and one of the few human organs whose cholesterol maintenance is still
      poorly understood. Challenges in studies of the retina include its complex
      multicellular and multilayered structure; unique cell types and functions; and
      specific physico-chemical environment. METHODOLOGY/PRINCIPAL FINDINGS: We
      isolated specimens of the neural retina (NR) and underlying retinal pigment
      epithelium (RPE)/choroid from six deceased human donors and evaluated them for
      expression of genes and proteins representing the major pathways of cholesterol
      input, output and regulation. Eighty-four genes were studied by PCR array, 16
      genes were assessed by quantitative real time PCR, and 13 proteins were
      characterized by immunohistochemistry. Cholesterol distribution among different
      retinal layers was analyzed as well by histochemical staining with filipin. Our
      major findings pertain to two adjacent retinal layers: the photoreceptor outer
      segments of NR and the RPE. We demonstrate that in the photoreceptor outer
      segments, cholesterol biosynthesis, catabolism and regulation via LXR and SREBP
      are weak or absent and cholesterol content is the lowest of all retinal layers.
      Cholesterol maintenance in the RPE is different, yet the gene expression also
      does not appear to be regulated by the SREBPs and varies significantly among
      different individuals. CONCLUSIONS/SIGNIFICANCE: This comprehensive investigation
      provides important insights into the relationship and spatial distribution of
      different pathways of cholesterol input, output and regulation in the NR-RPE
      region. The data obtained are important for deciphering the putative link between
      cholesterol and age-related macular degeneration, a major cause of irreversible
      vision loss in the elderly.

PMID- 22629471
TI  - Paxillin and Hic-5 interaction with vinculin is differentially regulated by Rac1
      and RhoA.
AB  - Cell migration is of paramount importance to organism development and maintenance
      as well as multiple pathological processes, including cancer metastasis. The
      RhoGTPases Rac1 and RhoA are indispensable for cell migration as they regulate
      cell protrusion, cell-extracellular matrix (ECM) interactions and force
      transduction. However, the consequences of their activity at a molecular level
      within the cell remain undetermined. Using a combination of FRET, FRAP and
      biochemical analyses we show that the interactions between the focal adhesion
      proteins vinculin and paxillin, as well as the closely related family member Hic
      5 are spatially and reciprocally regulated by the activity of Rac1 and RhoA.
      Vinculin in its active conformation interacts with either paxillin or Hic-5 in
      adhesions in response to Rac1 and RhoA activation respectively, while inactive
      vinculin interacts with paxillin in the membrane following Rac1 inhibition.
      Additionally, Rac1 specifically regulates the dynamics of paxillin as well as its
      binding partner and F-actin interacting protein actopaxin (alpha-parvin) in
      adhesions. Furthermore, FRET analysis of protein:protein interactions within cell
      adhesions formed in 3D matrices revealed that, in contrast to 2D systems vinculin
      interacts preferentially with Hic-5. This study provides new insight into the
      complexity of cell-ECM adhesions in both 2D and 3D matrices by providing the
      first description of RhoGTPase-coordinated protein:protein interactions in a
      cellular microenvironment. These data identify discrete roles for paxillin and
      Hic-5 in Rac1 and RhoA-dependent cell adhesion formation and maturation;
      processes essential for productive cell migration.

PMID- 22629472
TI  - Amygdala 14-3-3zeta as a novel modulator of escalating alcohol intake in mice.
AB  - Alcoholism is a devastating brain disorder that affects millions of people
      worldwide. The development of alcoholism is caused by alcohol-induced maladaptive
      changes in neural circuits involved in emotions, motivation, and decision-making.
      Because of its involvement in these processes, the amygdala is thought to be a
      key neural structure involved in alcohol addiction. However, the molecular
      mechanisms that govern the development of alcoholism are incompletely understood.
      We have previously shown that in a limited access choice paradigm, C57BL/6J mice
      progressively escalate their alcohol intake and display important behavioral
      characteristic of alcohol addiction, in that they become insensitive to quinine
      induced adulteration of alcohol. This study used the limited access choice
      paradigm to study gene expression changes in the amygdala during the escalation
      to high alcohol consumption in C57BL/6J mice. Microarray analysis revealed that
      changes in gene expression occurred predominantly after one week, i.e. during the
      initial escalation of alcohol intake. One gene that stood out from our analysis
      was the adapter protein 14-3-3zeta, which was up-regulated during the transition
      from low to high alcohol intake. Independent qPCR analysis confirmed the up
      regulation of amygdala 14-3-3zeta during the escalation of alcohol intake.
      Subsequently, we found that local knockdown of 14-3-3zeta in the amygdala, using
      RNA interference, dramatically augmented alcohol intake. In addition, knockdown
      of amygdala 14-3-3zeta promoted the development of inflexible alcohol drinking,
      as apparent from insensitivity to quinine adulteration of alcohol. This study
      identifies amygdala 14-3-3zeta as a novel key modulator that is engaged during
      escalation of alcohol use.

PMID- 22629473
TI  - Inconsistent Access to Food and Cardiometabolic Disease: The Effect of Food
      Insecurity.
AB  - Food insecurity is defined as limited or uncertain ability to acquire
      nutritionally adequate and safe foods in socially acceptable ways. The United
      States Department of Agriculture (USDA) has divided food insecurity into two
      categories: low food security and very low food security. Low food security is
      characterized by irregular access to food, binge eating when food is available,
      overconsumption of energy-dense foods, obesity, and even type 2 diabetes. This
      type of food insecurity occurs in impoverished urban areas of high-income
      countries such as the United States. In contrast, very low food security is
      distinctly different from low food security and can lead to undernutrition and
      frank starvation. Very low food security is found in developing countries in both
      rural areas and urban slums. In these countries, food insecurity is often
      exacerbated by natural disasters and climate changes that compromise food
      availability. With a focus on the social, economic, and behavioral factors that
      promote obesity and cardiometabolic disease in food insecure households in the
      United States, this review will first define the key terms and concepts
      associated with food insecurity. Then, the characteristics of food insecure
      households and the relationship to cardiometabolic disease will be discussed.
      Finally, the cardiac consequences of food insecurity in developing countries will
      be briefly described.

PMID- 22629474
TI  - Disease severity in patients infected with Leishmania mexicana relates to IL
      1beta.
AB  - Leishmania mexicana can cause both localized (LCL) and diffuse (DCL) cutaneous
      leishmaniasis, yet little is known about factors regulating disease severity in
      these patients. We analyzed if the disease was associated with single nucleotide
      polymorphisms (SNPs) in IL-1beta (-511), CXCL8 (-251) and/or the inhibitor IL-1RA
      (+2018) in 58 Mexican mestizo patients with LCL, 6 with DCL and 123 control
      cases. Additionally, we analyzed the in vitro production of IL-1beta by
      monocytes, the expression of this cytokine in sera of these patients, as well as
      the tissue distribution of IL-1beta and the number of parasites in lesions of LCL
      and DCL patients. Our results show a significant difference in the distribution
      of IL-1beta (-511 C/T) genotypes between patients and controls (heterozygous OR),
      with respect to the reference group CC, which was estimated with a value of 3.23,
      95% CI = (1.2, 8.7) and p-value = 0.0167), indicating that IL-1beta (-511 C/T)
      represents a variable influencing the risk to develop the disease in patients
      infected with Leishmania mexicana. Additionally, an increased in vitro production
      of IL-1beta by monocytes and an increased serum expression of the cytokine
      correlated with the severity of the disease, since it was significantly higher in
      DCL patients heavily infected with Leishmania mexicana. The distribution of IL
      1beta in lesions also varied according to the number of parasites harbored in the
      tissues: in heavily infected LCL patients and in all DCL patients, the cytokine
      was scattered diffusely throughout the lesion. In contrast, in LCL patients with
      lower numbers of parasites in the lesions, IL-1beta was confined to the cells.
      These data suggest that IL-1beta possibly is a key player determining the
      severity of the disease in DCL patients. The analysis of polymorphisms in CXCL8
      and IL-1RA showed no differences between patients with different disease
      severities or between patients and controls.

PMID- 22629475
TI  - Improved canine and human visceral leishmaniasis immunodiagnosis using
      combinations of synthetic peptides in enzyme-linked immunosorbent assay.
AB  - BACKGROUND: Zoonotic visceral leishmaniasis (VL) is a severe infectious disease
      caused by protozoan parasites of the genus Leishmania and the domestic dogs are
      the main urban parasite reservoir hosts. In Brazil, indirect fluorescence
      antibody tests (IFAT) and indirect enzyme linked immunosorbent assay (ELISA)
      using promastigote extracts are widely used in epidemiological surveys. However,
      their sensitivity and specificity have often been compromised by the use of
      complex mixtures of antigens, which reduces their accuracy allowing the
      maintenance of infected animals that favors transmission to humans. In this
      context, the use of combinations of defined peptides appears favorable.
      Therefore, they were tested by combinations of five peptides derived from the
      previously described Leishmania diagnostic antigens A2, NH, LACK and K39.
      METHODOLOGY/PRINCIPAL FINDINGS: Combinations of peptides derived A2, NH, LACK and
      K39 antigens were used in ELISA with sera from 44 human patients and 106 dogs.
      Improved sensitivities and specificities, close to 100%, were obtained for both
      sera of patients and dogs. Moreover, high sensitivity and specificity were
      observed even for canine sera presenting low IFAT anti-Leishmania antibody titers
      or from asymptomatic animals. CONCLUSIONS/SIGNIFICANCE: The use of combinations
      of B cell predicted synthetic peptides derived from antigens A2, NH, LACK and K39
      may provide an alternative for improved sensitivities and specificities for
      immunodiagnostic assays of VL.

PMID- 22629476
TI  - Surveillance of dengue fever virus: a review of epidemiological models and early
      warning systems.
AB  - Dengue fever affects over a 100 million people annually hence is one of the
      world's most important vector-borne diseases. The transmission area of this
      disease continues to expand due to many direct and indirect factors linked to
      urban sprawl, increased travel and global warming. Current preventative measures
      include mosquito control programs, yet due to the complex nature of the disease
      and the increased importation risk along with the lack of efficient prophylactic
      measures, successful disease control and elimination is not realistic in the
      foreseeable future. Epidemiological models attempt to predict future outbreaks
      using information on the risk factors of the disease. Through a systematic
      literature review, this paper aims at analyzing the different modeling methods
      and their outputs in terms of acting as an early warning system. We found that
      many previous studies have not sufficiently accounted for the spatio-temporal
      features of the disease in the modeling process. Yet with advances in technology,
      the ability to incorporate such information as well as the socio-environmental
      aspect allowed for its use as an early warning system, albeit limited
      geographically to a local scale.

PMID- 22629477
TI  - Elevated plasma IL-6 associates with increased risk of advanced fibrosis and
      cholangiocarcinoma in individuals infected by Opisthorchis viverrini.
AB  - Opisthorchis viverrini is considered among the most important of the food-borne
      trematodes due to its strong association with advanced periductal fibrosis and
      bile duct cancer (cholangiocarcinoma). We investigated the relationship between
      plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis
      and bile duct cancer from chronic Opisthorchis infection. We show that IL-6
      circulates in plasma at concentrations 58 times higher in individuals with
      advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221
      times higher in individuals with bile duct cancer than controls. We also observed
      a dose-response relationship between increasing levels of plasma IL-6 and
      increasing risk of advanced fibrosis and bile duct cancer; for example, in age
      and sex adjusted analyses, individuals with the highest quartiles of plasma IL-6
      had a 19 times greater risk of developing advanced periductal fibrosis and a 150
      times greater risk of developing of bile duct cancer than individuals with no
      detectable level of plasma IL-6. Finally, we show that a single plasma IL-6
      measurement has excellent positive predictive value for the detection of both
      advanced bile duct fibrosis and bile duct cancer in regions with high O.
      viverrini transmission. These data support our hypothesis that common mechanisms
      drive bile duct fibrosis and bile duct tumorogenesis from chronic O. viverrini
      infection. Our study also adds a unique aspect to the literature on circulating
      levels of IL-6 as an immune marker of hepatobiliary pathology by showing that
      high levels of circulating IL-6 in plasma are not related to infection with O.
      viverrini, but to the development of the advanced and often lethal pathologies
      resulting from chronic O. viverrini infection.

PMID- 22629478
TI  - Drug susceptibility in Leishmania isolates following miltefosine treatment in
      cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis.
AB  - BACKGROUND: With widespread resistance to antimonials in Visceral Leishmaniasis
      (VL) in the Indian subcontinent, Miltefosine (MIL) has been introduced as the
      first line therapy. Surveillance of MIL susceptibility in natural populations of
      Leishmania donovani is vital to preserve it and support the VL elimination
      program. METHODOLOGY AND PRINCIPAL FINDINGS: We measured in vitro susceptibility
      towards MIL and paromomycin (PMM) in L. donovani isolated from VL and PKDL, pre-
      and post-treatment cases, using an amastigote-macrophage model. MIL
      susceptibility of post-treatment isolates from cured VL cases (n = 13, mean
      IC(50)+/-SD = 2.43+/-1.44 uM), was comparable (p>0.05) whereas that from relapses
      (n = 3, mean IC(50) = 4.72+/-1.99 uM) was significantly higher (p = 0.04) to that
      of the pre-treatment group (n = 6, mean IC(50) = 1.86+/-0.75 uM). In PKDL, post
      treatment isolates (n = 3, mean IC(50) = 16.13+/-2.64 uM) exhibited significantly
      lower susceptibility (p = 0.03) than pre-treatment isolates (n = 5, mean IC(50) =
      8.63+/-0.94 uM). Overall, PKDL isolates (n = 8, mean IC(50) = 11.45+/-4.19 uM)
      exhibited significantly higher tolerance (p<0.0001) to MIL than VL isolates (n =
      22, mean IC(50) = 2.58+/-1.58 uM). Point mutations in the miltefosine transporter
      (LdMT) and its beta subunit (LdRos3) genes previously reported in parasites with
      experimentally induced MIL resistance were not present in the clinical isolates.
      Further, the mRNA expression profile of these genes was comparable in the pre-
      and post-treatment isolates. Parasite isolates from VL and PKDL cases were
      uniformly susceptible to PMM with respective mean IC(50) = 7.05+/-2.24 uM and
      6.18+/-1.51 uM. CONCLUSION: The in vitro susceptibility of VL isolates remained
      unchanged at the end of MIL treatment; however, isolates from relapsed VL and
      PKDL cases had lower susceptibility than the pre-treatment isolates. PKDL
      isolates were more tolerant towards MIL in comparison with VL isolates. All
      parasite isolates were uniformly susceptible to PMM. Mutations in the LdMT and
      LdRos3 genes as well as changes in the expression of these genes previously
      correlated with experimental resistance to MIL could not be verified for the
      field isolates.

PMID- 22629479
TI  - Junin virus infection activates the type I interferon pathway in a RIG-I
      dependent manner.
AB  - Junin virus (JUNV), an arenavirus, is the causative agent of Argentine
      hemorrhagic fever, an infectious human disease with 15-30% case fatality. The
      pathogenesis of AHF is still not well understood. Elevated levels of interferon
      and cytokines are reported in AHF patients, which might be correlated to the
      severity of the disease. However the innate immune response to JUNV infection has
      not been well evaluated. Previous studies have suggested that the virulent strain
      of JUNV does not induce IFN in human macrophages and monocytes, whereas the
      attenuated strain of JUNV was found to induce IFN response in murine macrophages
      via the TLR-2 signaling pathway. In this study, we investigated the interaction
      between JUNV and IFN pathway in human epithelial cells highly permissive to JUNV
      infection. We have determined the expression pattern of interferon-stimulated
      genes (ISGs) and IFN-beta at both mRNA and protein levels during JUNV infection.
      Our results clearly indicate that JUNV infection activates the type I IFN
      response. STAT1 phosphorylation, a downstream marker of activation of IFN
      signaling pathway, was readily detected in JUNV infected IFN-competent cells. Our
      studies also demonstrated for the first time that RIG-I was required for IFN
      production during JUNV infection. IFN activation was detected during infection by
      either the virulent or attenuated vaccine strain of JUNV. Curiously, both virus
      strains were relatively insensitive to human IFN treatment. Our studies
      collectively indicated that JUNV infection could induce host type I IFN response
      and provided new insights into the interaction between JUNV and host innate
      immune system, which might be important in future studies on vaccine development
      and antiviral treatment.

PMID- 22629481
TI  - Wide-band negative permeability of nonlinear metamaterials.
AB  - We propose a novel way to achieve an exceptionally wide frequency range where
      metamaterial possesses negative effective permeability. This can be achieved by
      employing a nonlinear response of metamaterials. We demonstrate that, with an
      appropriate design, a frequency band exceeding 100% is available for a range of
      signal amplitudes. Our proposal provides a significant improvement over the
      linear approach, opening a road towards broadband negative refraction and its
      applications.

PMID- 22629480
TI  - Salivary gland transcriptomes and proteomes of Phlebotomus tobbi and Phlebotomus
      sergenti, vectors of leishmaniasis.
AB  - BACKGROUND: Phlebotomus tobbi is a vector of Leishmania infantum, and P. sergenti
      is a vector of Leishmania tropica. Le. infantum and Le. tropica typically cause
      visceral or cutaneous leishmaniasis, respectively, but Le. infantum strains
      transmitted by P. tobbi can cause cutaneous disease. To better understand the
      components and possible implications of sand fly saliva in leishmaniasis, the
      transcriptomes of the salivary glands (SGs) of these two sand fly species were
      sequenced, characterized and compared. METHODOLOGY/PRINCIPAL FINDINGS: cDNA
      libraries of P. tobbi and P. sergenti female SGs were constructed, sequenced, and
      analyzed. Clones (1,152) were randomly picked from each library, producing 1,142
      high-quality sequences from P. tobbi and 1,090 from P. sergenti. The most
      abundant, secreted putative proteins were categorized as antigen 5-related
      proteins, apyrases, hyaluronidases, D7-related and PpSP15-like proteins, ParSP25
      like proteins, PpSP32-like proteins, yellow-related proteins, the 33-kDa salivary
      proteins, and the 41.9-kDa superfamily of proteins. Phylogenetic analyses and
      multiple sequence alignments of putative proteins were used to elucidate
      molecular evolution and describe conserved domains, active sites, and catalytic
      residues. Proteomic analyses of P. tobbi and P. sergenti SGs were used to confirm
      the identification of 35 full-length sequences (18 in P. tobbi and 17 in P.
      sergenti). To bridge transcriptomics with biology P. tobbi antigens,
      glycoproteins, and hyaluronidase activity was characterized. CONCLUSIONS: This
      analysis of P. sergenti is the first description of the subgenus Paraphlebotomus
      salivary components. The investigation of the subgenus Larroussius sand fly P.
      tobbi expands the repertoire of salivary proteins in vectors of Le. infantum.
      Although P. tobbi transmits a cutaneous form of leishmaniasis, its salivary
      proteins are most similar to other Larroussius subgenus species transmitting
      visceral leishmaniasis. These transcriptomic and proteomic analyses provide a
      better understanding of sand fly salivary proteins across species and subgenera
      that will be vital in vector-pathogen and vector-host research.

PMID- 22629482
TI  - Quantitative assessment on the cloning efficiencies of lentiviral transfer
      vectors with a unique clone site.
AB  - Lentiviral vectors (LVs) are powerful tools for transgene expression in vivo and
      in vitro. However, the construction of LVs is of low efficiency, due to the large
      sizes and lack of proper clone sites. Therefore, it is critical to develop
      efficient strategies for cloning LVs. Here, we reported a combinatorial strategy
      to efficiently construct LVs using EGFP, hPlk2 wild type (WT) and mutant genes as
      inserts. Firstly, site-directed mutagenesis (SDM) was performed to create BamH I
      site for the inserts; secondly, pWPI LV was dephosphorylated after BamH I
      digestion; finally, the amounts and ratios of the insert and vector DNA were
      optimized to increase monomeric ligation. Our results showed that the total
      percentage of positive clones was approximately 48%+/-7.6%. Using this method,
      almost all the vectors could be constructed through two or three minipreps.
      Therefore, our study provided an efficient method for constructing large-size
      vectors.

PMID- 22629483
TI  - Skull metastasis as initial manifestation of pulmonary epithelial-myoepithelial
      carcinoma: a case report of an unusual case.
AB  - Epithelial-myoepithelial carcinoma (EMC) of the lung is rare and is considered to
      be low-grade malignancy. Intracranial metastasis of pulmonary EMC has not
      previously been reported according to our search of the literature. We report a
      case of skull metastasis as the initial manifestation of pulmonary EMC. An 81
      year-old man complained of left leg motor weakness. Neurological examination
      showed left hemiparesis. Computed tomography and magnetic resonance imaging
      revealed an osteolytic tumor in the right frontal bone with invasion to the dura
      and subdural space, attached to the superior sagittal sinus. Subtotal removal of
      the tumor was performed, and the left hemiparesis showed improvement.
      Histopathological study revealed the tumor to consist of epithelial and
      myoepithelial cells. Pulmonary EMC was diagnosed. The MIB-1 index in primary
      lesion was approximately 10%. The skull and dura are possible sites for
      metastasis from pulmonary EMC. The MIB-1 index is a predictive marker of
      malignant potential.

PMID- 22629484
TI  - Ectopic prolactinoma within the sphenoidal sinus associated with empty sella.
AB  - BACKGROUND: Pituitary adenomas are a common cause of endocrinal dysfunction,
      which comprise 10-20% of all intracranial tumors. Although almost all of them
      arise within the sella turcica, there are some rare cases in which a pituitary
      adenoma is located outside the intrasellar region, so it is defined as an ectopic
      pituitary adenoma (EPA). CASE DESCRIPTION: We described a case of a 31-year-old
      male with a serum prolactin (PRL) value of 240 ng/ml Magnetic resonance imaging
      (MRI) showed a space-occupying mass within the sphenoid sinus (SS) which
      partially enhanced by gadolinium. MRI did not reveal any sellar floor defect and
      an empty sella was detected. As dopamine agonist treatment had failed in lowering
      the serum PRL level, he underwent surgical treatment. A transsphenoidal approach
      without opening the sellar floor was performed using an operating microscope and
      the lesion within the SS was completely removed. CONCLUSION: Although
      intrasphenoidal EPAs are rare findings, the presence of an endocrine disorder
      related to pituitary hormones, and a space-occupying mass within the SS
      associated with either a normal sellar pituitary gland or an empty sella must
      lead us to suspect this diagnosis.

PMID- 22629485
TI  - Radiation associated tumors following therapeutic cranial radiation.
AB  - BACKGROUND: A serious, albeit rare, sequel of therapeutic ionizing radiotherapy
      is delayed development of a new, histologically distinct neoplasm within the
      radiation field. METHODS: We identified 27 cases, from a 10-year period, of
      intracranial tumors arising after cranial irradiation. The original lesions for
      which cranial radiation was used for treatment included: tinea capitis (1), acute
      lymphoblastic leukemia (ALL; 5), sarcoma (1), scalp hemangioma (1), cranial nerve
      schwannoma (1) and primary (13) and metastatic (1) brain tumors, pituitary tumor
      (1), germinoma (1), pinealoma (1), and unknown histology (1). Dose of cranial
      irradiation ranged from 1800 to 6500 cGy, with a mean of 4596 cGy. Age at cranial
      irradiation ranged from 1 month to 43 years, with a mean of 13.4 years. RESULTS:
      Latency between radiotherapy and diagnosis of a radiation-induced neoplasm ranged
      from 4 to 47 years (mean 18.8 years). Radiation-induced tumors included:
      meningiomas (14), sarcomas (7), malignant astrocytomas (4), and medulloblastomas
      (2). Data were analyzed to evaluate possible correlations between gender, age at
      irradiation, dose of irradiation, latency, use of chemotherapy, and radiation
      induced neoplasm histology. Significant correlations existed between age at
      cranial irradiation and development of either a benign neoplasm (mean age 8.5
      years) versus a malignant neoplasm (mean age 20.3; P = 0.012), and development of
      either a meningioma (mean age 7.0 years) or a sarcoma (mean age 27.4 years; P =
      0.0001). There was also a significant positive correlation between latency and
      development of either a meningioma (mean latency 21.8 years) or a sarcoma (mean
      latency 7.7 years; P = 0.001). The correlation between dose of cranial
      irradiation and development of either a meningioma (mean dose 4128 cGy) or a
      sarcoma (mean dose 5631 cGy) approached significance (P = 0.059). CONCLUSIONS:
      Our study is the first to show that younger patients had a longer latency period
      and were more likely to have lower-grade lesions (e.g. meningiomas) as a
      secondary neoplasm, while older patients had a shorter latency period and were
      more likely to have higher-grade lesions (e.g. sarcomas).

PMID- 22629486
TI  - Preoperative hyperglycemia and complication risk following neurosurgical
      intervention: A study of 918 consecutive cases.
AB  - BACKGROUND: Little is known about the relation between preoperative glycemic
      state and neurosurgical outcomes. Improved understanding of this relationship may
      identify patients at increased risk of complicated recovery and guide
      postoperative treatment strategies. METHODS: Data were collected about 918
      consecutive craniotomy or spine-related neurosurgical cases at the University of
      Michigan Hospitals. Univariate statistics, bivariate chi-square tests, and
      analysis of variance were used to assess relations between preoperative blood
      glucose, demographics, medical comorbidities, systemic glucocorticoid use, and
      postoperative complication risk and postoperative hospital and intensive care
      unit (ICU) stay. We fit a multivariable logistic regression model of 30-day
      complication risk by preoperative blood glucose adjusted for potential
      confounders, and used analysis of covariance to assess the relation between
      preoperative blood glucose and hospital, as well as ICU stay, adjusted for
      potential confounders. RESULTS: Among all patients, 56.1% had peri-operative
      blood glucose levels below 100 mg/dl. 20.7% had levels from 100 to 120 mg/dl,
      16.3% had levels from 121 to 160 mg/dl, and 6.9% had levels greater than 160
      mg/dl. In multivariable regression models, blood glucose greater than 120 mg/dl
      was associated with increased risk of postoperative complications at all levels.
      Analysis of covariance showed that preoperative blood glucose above 120 mg/dl was
      associated with both increased length of ICU stay and length of hospital stay.
      CONCLUSIONS: Our findings suggest that even mild preoperative hyperglycemia is a
      predictor of postoperative complication risk, and prolonged hospital and ICU stay
      following neurosurgical intervention. Tight glycemic control may be in order when
      attempting to reduce risk of complications and limit postoperative recovery time.

PMID- 22629487
TI  - Trigeminal neuralgia: Assessment of neurovascular decompression by 3D fast
      imaging employing steady-state acquisition and 3D time of flight multiple
      overlapping thin slab acquisition magnetic resonance imaging.
AB  - BACKGROUND: Trigeminal neuralgia is most commonly caused by vascular compression
      at the trigeminal nerve (TN) root entry zone. Microvascular decompression (MVD)
      has been established as a useful treatment. Outcome depends on the correct
      identification of the compression site and its adequate decompression at surgery.
      Preoperative identification of neurovascular compression might predict which
      patients will benefit from MVD. Management of persistent or recurrent trigeminal
      neuralgia after an MVD is a baffling problem for neurosurgeons. An accurate
      neuroradiological evaluation of the TN padding following a failed MVD might help
      identify the underlying cause and plan further treatment. CASE DESCRIPTION: A 68
      year-old female presented with a right-sided trigeminal neuralgia (V3) refractory
      to medical therapy. A high-resolution three-dimensional magnetic resonance
      imaging (3D MRI) study included fast imaging employing steady-state acquisition
      (FIESTA) and time of flight multiple overlapping thin slab acquisition (TOF
      MOTSA) sequences to evaluate the neurovascular anatomy in the cerebellopontine
      angle. An unambiguous compression of the right TN at the rostral-medial site by
      the superior cerebellar artery (SCA) was identified. The SCA loop compressing the
      TN was identical in location and configuration to that predicted in the
      preoperative study. After the MVD, the patient was relieved from her pain and a
      postoperative high-resolution 3D MRI study confirmed the appropriate placement of
      the Teflon implant between the TN and SCA. CONCLUSION: To our knowledge, this is
      the first report that characterizes the proper TN padding by high-resolution 3D
      MRI after trigeminal MVD. The present case also emphasizes the importance of
      performing a 3D MRI in patients with trigeminal neuralgia to anticipate the
      surgeon's view and predict the outcome after MVD.

PMID- 22629488
TI  - Concurrent intracranial and spinal arteriovenous malformations: Report of two
      pediatric cases and literature review.
AB  - BACKGROUND: Concurrent intracranial and spinal arteriovenous malformations (AVMs)
      are very rare with only a few cases being reported in literature. Two of the rare
      concurrent intracranial and spinal AVM cases are presented. CASE DESCRIPTION:
      Case 1 is a 12-year-old girl with headache and motor disturbances in the lower
      limbs. Her spinal and brain angiogram was done and she was diagnosed to have a
      spinal AVM at level T8-T9 and an intracranial AVM in the left mesial temporal
      lobe. Her spinal AVM was embolized, while no treatment was given for her
      intracranial AVM. Case 2 is a 10-year-old girl who presented with headache and
      quadriparesis. Her brain and spinal angiogram revealed an intracranial AVM in the
      left parietal lobe and a spinal AVM at level C2, respectively. Craniotomy and
      excision was done for her intracranial AVM and embolization for the spinal AVM.
      CONCLUSION: It is proposed that multiple AVMs may be a result of yet unrevealed
      pathogenesis or strong embryogenetic anomaly, which may be different from that
      involved in single AVM. With lack of consensus over the best therapeutic
      strategy, multimodality treatment based on the individual's needs is suggested.

PMID- 22629489
TI  - Delay in diagnosis of primary intradural spinal cord tumors.
AB  - BACKGROUND: It has been our impression in recent years that there is a
      significant delay in diagnosis (DID) of patients in Israel harboring intradural
      spinal cord tumors (IDSCTs). DID can lead to irreversible deficits and
      unnecessary suffering. Our goal was to identify the incidence and the specific
      reasons for DID of IDSCTs in patients operated upon at our institution. METHODS:
      A retrospective record review, with additional telephone survey, of 101 patients
      operated upon at our institute between the years 1996 and 2009 was conducted. The
      patients who were not diagnosed locally and those who were diagnosed during
      routine spinal imaging studies as part of their basic disease check-up were
      excluded. Accordingly, neurofibromatosis and medical tourist patients were
      excluded. RESULTS: The clinical presentation of IDSCTs in our study was similar
      to the descriptions given in previous reports. The average age was 41.9 +/- 23.3
      years. Most tumors were ependymomas, astrocytomas, and schwannomas. The most
      common symptoms were motor or sensory disturbance, back pain, walking
      disturbance, and sphincter control deficit. The median time to diagnosis was 12.0
      +/- 37.0 months (range 3 days to 20 years). We found DID in 82.2% of the cases.
      62.4% of the cases were defined as "unreasonable delay." The most common reasons
      for DID were "classical symptoms with a wrong diagnosis" and "delayed imaging."
      CONCLUSIONS: Based on the results of this study, the incidence of unreasonable
      delays in diagnosis of primary IDSCTs in Israel is very high. In order to shorten
      the time to diagnosis, primary and secondary care physicians need to increase
      their awareness of symptoms that may be associated with these lesions. We hereby
      offer feedback for care providers, relevant to the diagnostic workup of these
      patients. Such a feedback must be delivered by neurosurgeons to the community
      they are serving.

PMID- 22629490
TI  - Pontine venous congestion due to dural arteriovenous fistula of the cavernous
      sinus: Case report and review of the literature.
AB  - BACKGROUND: We report herein a case of cavernous sinus (CS)-dural arteriovenous
      fistula (DAVF) with brainstem venous congestion that was successfully treated by
      transarterial embolization, followed by radiotherapy. CASE DESCRIPTION: An 80
      year-old woman presented with right eye chemosis and left hemiparesis. T2
      weighted magnetic resonance imaging showed hyperintensity of the pons. Diagnostic
      cerebral angiography demonstrated CS-DAVF draining into the right superior
      orbital vein and petrosal vein, and fed by bilateral internal and external
      carotid arteries. Transarterial embolization was performed and followed by
      radiotherapy, resulting in resolution of the pontine lesion and neurological and
      ophthalmological symptoms within 5 months. CONCLUSIONS: We also review the
      literature regarding therapy for CS-DAVF with brainstem venous congestion. Once
      CS-DAVF with venous congestion of the brainstem has been definitively diagnosed,
      immediate therapy is warranted. Treatment with transarterial embolization
      followed by radiation may be an important option for elderly patients when
      transvenous or transarterial embolization is not an option.

PMID- 22629491
TI  - DECRA...Where do we go from here?

PMID- 22629493
TI  - Celebrating life with Rita Levi-Montalcini: A hundred years and more.

PMID- 22629494
TI  - The exaptation of endocrine pharmacology.

PMID- 22629492
TI  - Primary spinal extradural Ewing's sarcoma (primitive neuroectodermal tumor):
      Report of a case and meta-analysis of the reported cases in the literature.
AB  - BACKGROUND: Primary spinal primitive neuroectodermal tumors (PNET) and/or spinal
      extraskeletal Ewing's sarcoma family tumors (ESET) are rare lesions appearing in
      the spinal extradural space. One hundred forty-one primary spinal PNETs,
      including 29 intramedullary lesions, have been reported in the literature.
      Encountering a case of primary epidural EES/peripheral PNET (pPNET) in sacral
      level, which is the fifth one occurring at this level in the literature, we have
      tried to conduct a meta-analysis of the reported cases. CASE DESCRIPTION: A 44
      year-old lady with epidural EES/pPNET is reported here. She was once operated for
      L5/S1 herniated disc, which did not ameliorate her symptoms. The clinical,
      imaging, surgical, and histopathologic characteristics of our case are presented
      and wide search of the literature is also done. All the reports were level 3 or
      less evidences and most of the series had missing parts. 106 cases of primary
      intraspinal (extradural/extramedullary-intradural) EES/pPNET and 29 cases of
      primary intramedullary PNET (CNS-PNET) have been reported in the literature. The
      most common clinical presentation in both entities was muscle weakness
      proportionate to the tumor location. Distant metastasis occurred in 38 of 99
      (38%) cases of primary intraspinal EES/pPNET, while the rate of metastasis was
      48% in patients with PNETs occurring in the intramedullary region (P > 0.05). One
      year survival rate of the patients who underwent chemo-radiation after total or
      subtotal resection was better than those who did not receive chemotherapy or
      radiotherapy, or did not have total or subtotal resection. However, this
      difference was not repeated in 2-year survival rate in any of the tumor groups.
      CONCLUSION: It seems that total or subtotal removal of the tumor and adjuvant
      chemo- and radiation therapy can improve the outcome in these patients.

PMID- 22629495
TI  - The eye as a window to rare endocrine disorders.
AB  - The human eye, as an organ, can offer critical clues to the diagnosis of various
      systemic illnesses. Ocular changes are common in various endocrine disorders such
      as diabetes mellitus and Graves' disease. However there exist a large number of
      lesser known endocrine disorders where ocular involvement is significant.
      Awareness of these associations is the first step in the diagnosis and management
      of these complex patients. The rare syndromes involving the pituitary
      hypothalamic axis with significant ocular involvement include Septo-optic
      dysplasia, Kallman's syndrome, and Empty Sella syndrome all affecting the optic
      nerve at the optic chiasa. The syndromes involving the thyroid and parathyroid
      glands that have ocular manifestations and are rare include Mc Cune Albright
      syndrome wherein optic nerve decompression may occur due to fibrous dysplasia,
      primary hyperparathyroidism that may present as red eye due to scleritis and
      Ascher syndrome wherein ptosis occurs. Allgrove's syndrome, Cushing's disease,
      and Addison's disease are the rare endocrine syndromes discussed involving the
      adrenals and eye. Ocular involvement is also seen in gonadal syndromes such as
      Bardet Biedl, Turner's, Rothmund's, and Klinefelter's syndrome. This review also
      highlights the ocular manifestation of miscellaneous syndromes such as Werner's,
      Cockayne's, Wolfram's, Kearns Sayre's, and Autoimmune polyendocrine syndrome. The
      knowledge of these relatively uncommon endocrine disorders and their ocular
      manifestations will help an endocrinologist reach a diagnosis and will alert an
      ophthalmologist to seek specialty consultation of an endocrinologist when
      encountered with such cases.

PMID- 22629496
TI  - Bisphenol A in dental sealants and its estrogen like effect.
AB  - Bisphenol A or BPA-based epoxy resins are widely used in the manufacture of
      commercial products, including dental resins, polycarbonate plastics, and the
      inner coating of food cans. BPA is a precursor to the resin monomer Bis-GMA.
      During the manufacturing process of Bis-GMA dental sealants, Bisphenol A (BPA)
      might be present as an impurity or as a degradation product of Bis-DMA through
      esterases present in saliva. Leaching of these monomers from resins can occur
      during the initial setting period and in conjunction with fluid sorption and
      desorption over time and this chemical leach from dental sealants may be
      bioactive. Researchers found an estrogenic effect with BPA, Bis-DMA, and Bis-GMA
      because BPA lacks structural specificity as a natural ligand to the estrogen
      receptor. It generated considerable concern regarding the safety of dental resin
      materials. This review focuses on the BPA in dental sealants and its estrogen
      like effect.

PMID- 22629497
TI  - Teriparatide - Indications beyond osteoporosis.
AB  - Osteoporosis is a condition of impaired bone strength that results in an
      increased risk of fracture. The current and most popular pharmacological options
      for the treatment of osteoporosis include antiresorptive therapy, in particular,
      oral bisphosphonates (alendronate, risedronate, ibandronate). Anabolic agents
      like teriparatide have widened our therapeutic options. They act by directly
      stimulating bone formation and improving bone mass quantity and quality. Two
      forms of recombinant human parathyroid hormone (PTH) are available : full-length
      PTH (PTH 1-84; approved in the EU only) and the 1-34 N-terminal active fragment
      of PTH (teriparatide, US FDA approved). This review aims to discuss the benefits
      of teriparatide beyond the currently licensed indications like fracture healing,
      dental stability, osteonecrosis of jaw, hypoparathyroidism, and hypocalcemia.

PMID- 22629498
TI  - Osteoanabolics.
AB  - Osteoporosis is characterized by reduced bone mass, impaired bone quality, and a
      propensity to fracture. An "osteoanabolic" should be referred to any therapy that
      helps increase bone mass. Bone mass represents 80% of bone mechanical strength. A
      low bone mass therefore provides the strongest association of future risk of
      fracture. This review aims to discuss all available and future therapies that
      attempt to increase bone mass be it organic or inorganic.

PMID- 22629499
TI  - Calcium and bone disorders in pregnancy.
AB  - Significant transplacental calcium transfer occurs during pregnancy, especially
      during the last trimester, to meet the demands of the rapidly mineralizing fetal
      skeleton. Similarly, there is an obligate loss of calcium in the breast milk
      during lactation. Both these result in considerable stress on the bone mineral
      homeostasis in the mother. The maternal adaptive mechanisms to conserve calcium
      are different in pregnancy and lactation. During pregnancy, increased intestinal
      absorption of calcium from the gut mainly due to higher generation of calcitriol
      (1,25 dihydroxy vitamin D) helps in maintaining maternal calcium levels. On the
      other hand, during lactation, the main compensatory mechanism is skeletal
      resorption due to increased generation of parathormone related peptide (PTHrP)
      from the breast. Previous studies suggest that in spite of considerable changes
      in bone mineral metabolism during pregnancy, parity and lactation are not
      significantly associated with future risk for osteoporosis. However, in India,
      the situation may not be the same as a significant proportion of pregnancies
      occur in the early twenties when peak bone mass is not yet achieved. Further,
      malnutrition, anemia and vitamin D deficiency are commonly encountered in this
      age group. This may have an impact on future bone health of the mother. It may
      also probably provide an opportunity for health care providers for prevention.
      Other metabolic bone diseases like hypoparathyroidism, hyperparathyroidism and
      pseudohypoparathyroidism are rarely encountered in pregnancy. Their clinical
      implications and management are also discussed.

PMID- 22629500
TI  - Hypothyroidism in pregnancy.
AB  - Pregnancy is a period that places great physiological stress on both the mother
      and the fetus. When pregnancy is compounded by endocrine disorders such as
      hypothyroidism, the potential for maternal and fetal adverse outcomes can be
      immense. While a lot of attention has been focused on the adverse fetal outcomes
      consequent to hypothyroidism, attention is also being gradually directed towards
      the adverse maternal outcomes of this disorder. Role of antibody positivity in
      influencing outcomes in a euthyroid woman, also needs further clarification.
      Prompt diagnosis and treatment of hypothyroidism in pregnancy is very essential.
      Subclinical hypothyroidism also needs to be detected and treated to prevent
      adverse outcomes, especially maternal. Since women with hypothyroidism during
      pregnancy, especially of the autoimmune variety might have a flare up of the
      disorder post-partum, or might continue to require thyroxine replacement post
      partum, adequate follow-up is mandatory. While targeted case finding is generally
      practised, recent evidence seems to indicate that universal screening might be a
      better option. In conclusion, routine screening, early confirmation of diagnosis
      and prompt treatment. Allied with regular post-partum follow up, is required to
      ensure favourable maternal and fetal outcomes.

PMID- 22629501
TI  - Imaging of the thyroid: Recent advances.
AB  - Although thyroid scintigraphy and ultrasound continues to be the mainstay of the
      diagnostic imaging of the thyroid gland, there have been several recent advances
      that are of interest to both radiologists and endocrinologists. In this review
      article, the authors discuss recent progress in imaging of the thyroid by use of
      radionuclide imaging including single photon-emission computed
      tomography/positron emission tomography, ultrasonography (USG), USG elastography,
      computed tomography (CT), magnetic resonance imaging (MRI), and optical coherence
      tomography.

PMID- 22629502
TI  - The eunuchs of India: An endocrine eye opener.
AB  - There are established guidelines for the endocrine and overall treatment of
      transsexual persons. These guidelines provide information about the optimal
      endocrine management of male-to-female and female-to-male transsexual persons.
      India has a large community of eunuchs, also known as hijras, who are men with
      gender identity disorders. While this community has been studied from a social
      and medical point of new, no endocrine work has been done in them. This
      exploratory article tries to discuss the endocrine status, health, and management
      of the eunuchs.

PMID- 22629503
TI  - Oral manifestations in growth hormone disorders.
AB  - Growth hormone is of vital importance for normal growth and development.
      Individuals with growth hormone deficiency develop pituitary dwarfism with
      disproportionate delayed growth of skull and facial skeleton giving them a small
      facial appearance for their age. Both hyper and hypopituitarism have a marked
      effect on development of oro-facial structures including eruption and shedding
      patterns of teeth, thus giving an opportunity to treating dental professionals to
      first see the signs and symptoms of these growth disorders and correctly diagnose
      the serious underlying disease.

PMID- 22629504
TI  - Molecular genetic analysis of CYP21A2 gene in patients with congenital adrenal
      hyperplasia.
AB  - CONTEXT: Congenital adrenal hyperplasia (CAH) is one of the inborn errors of
      metabolic disorder inherited in an autosomal recessive manner caused by the
      defects in the steroid 21 hydroxylase CYP21A2 gene. We analyzed the genotype of
      62 patients with classic CAH. AIMS: To find out the underlying mutations of
      CYP21A2 gene. SETTINGS AND DESIGN: Cohort of CAH patients. MATERIALS AND METHODS:
      Sixty-two patients with CAH were recruited from the endocrine clinic at AIIMS.
      Electrochemiluminiscence method was used for estimating the levels of cortisol.
      Radioimmunoassay kit-based method was used for estimating the 17 OHP levels.
      Polymerase chain reaction amplification was done using specific primers to amply
      the CYP21A2 gene. STATISTICAL ANALYSIS USED: Statistical analysis was done by
      using Epi Info Version 3.5.1.2008. RESULTS: Out of 62 patients, 50 were simple
      virilizers (SV) and 12 were salt wasters (SW). Fifty-six were females and six
      were males. Five 46, XX children were reared as males. Age at presentation varied
      from 8 months to 38 years. Molecular genetic analysis revealed that the highest
      number of patients harboured (In 2) IVS2-13 A/C > G (48%), followed by p.P30L
      (46%), p.Q318X (35%), (D 8 bp) deletion 8 bp (26%), p.I172N (26%), and p. R356W
      (20%) mutations. CONCLUSION: This is among the few studies to analyze the
      mutational spectrum of CYP21A2 gene in a large CAH cohort from India. Molecular
      diagnosis of CYP21A2 gene should be considered as part of the CAH evaluation to
      assess the risk of the patients/parents/siblings and to offer genetic counseling.

PMID- 22629505
TI  - Low dose adrenocorticotropic hormone test and adrenal insufficiency in critically
      ill acquired immunodeficiency syndrome patients.
AB  - CONTEXT: Prevalence of adrenal insufficiency (AI) is not uncommon in HIV infected
      population. However, AI is rarely diagnosed in clinical practice because many
      patients have non-specific symptoms and signs. Critical illness in such patients
      further complicates the evaluation of adrenal function. A 1MUgm ACTH test can be
      used for diagnosis, since it results in more physiological levels of ACTH. A
      serum cortisol of <18 MUg/dL, 30 or 60-minutes after ACTH test has been accepted
      as indicative of AI, but many experts advocate the normal cortisol response
      should exceed 25 MUg/dL, in critically ill patients. AIM: To determine the
      prevalence of AI in critically ill AIDS patients, by using 1 MUg ACTH test and
      also, to compare the diagnostic criteria for adrenal insufficiency between
      cortisol response of <18 MUg/dL and <25 MUg/dL. SETTINGS AND DESIGN: This
      prospective study was done in the Department of Medicine. MATERIALS AND METHODS:
      After taking blood for basal plasma cortisol from AIDS affected fifty adult men
      and women aged over 18 yrs, 1 MUg ACTH was given intravenously, and blood samples
      were again collected at 30 and 60 minutes for plasma cortisol estimation.
      STATISTICAL ANALYSIS: It was done by Mann-Whitney test. RESULTS: Prevalence of AI
      was 74% (37 patients) and 92% (46 patients), when the peak stimulated cortisol
      level of <18 MUg/dL and <25 MUg/dL, respectively, was used. CONCLUSION: AI is
      more prevalent in critically ill AIDS patients. Hence, this test can be performed
      for early intervention and better management.

PMID- 22629506
TI  - Behavioral aggressiveness in boys with sexual precocity.
AB  - BACKGROUND: Some boys with sexual precocity are known to have behavioral problems
      like increased physical and verbal aggression and school and social
      maladjustments. It is believed to be due to premature androgen exposure. However,
      it is not clear why only some develop this problem, difference in etiology could
      be one explanation. AIM: The aim of the study is to assess behavioral aggression
      in boys with sexual precocity due to different disorders. MATERIALS AND METHODS:
      Seven children, ages three to seven years, were enrolled for this study. Two were
      diagnosed to have congenital adrenal hyperplasia (CAH), three had testotoxicosis,
      while two had central precocious puberty. Parents of children with precocious
      puberty underwent the (CASP) questionnaire (children's aggression scale-parent
      version). RESULTS: Testosterone levels were high in all patients. Parents denied
      any history of physical or verbal aggression in the two boys with CAH. Their CASP
      rating was 0. In contrast, the CASP ratings in the two boys with testotoxicosis
      and the two with precocious puberty for five domains ranged from 3.1 - 24.2, 2.6 
      8.3,1-5.6,0 - 7.1, and 0 - 1, respectively. In the present study, increased
      aggression was seen among all the patients with testotoxicosis and both with
      precocious puberty. In contrast, there were no symptoms of either increased
      verbal or physical aggression in either of the two patients with CAH.
      CONCLUSIONS: The hormonal milieu in the boys with CAH versus those with sexual
      precocity due to other causes differed in terms of cortisol and androgen
      precursors. The androgen excess in CAH children was a consequence of cortisol
      deficiency. It is possible that cortisol sufficiency is required for androgen
      mediated behavioral effects.

PMID- 22629507
TI  - Evaluation of GnRH analogue testing in diagnosis and management of children with
      pubertal disorders.
AB  - CONTEXT: Gonadotrophin releasing hormone (GnRH) stimulation test is pivotal in
      the assessment of children with pubertal disorders. However, lack of availability
      and high cost often result in the test falling into disfavor. We routinely use
      the GnRH analogue stimulation test as an alternative at our center. AIM: To
      present the data on children with endocrine disorders who underwent GnRH agonist
      stimulation test in pediatric endocrine clinic of a tertiary care referral
      hospital. SETTING AND DESIGN: Pediatric endocrine clinic of a tertiary care
      referral hospital. Retrospective analysis of case records. MATERIALS AND METHODS:
      The details pertaining to clinical and radiological parameters and hormonal tests
      were retrieved from case records of 15 children who underwent GnRH agonist
      stimulation test from May 2010 to April 2011. RESULTS: Indications for testing
      with GnRH analogue were evaluation of delayed puberty, diagnosis of precocious
      puberty, assessment of hormonal suppression in treatment of precocious puberty
      and micropenis in two, nine, three and one cases, respectively. The results of
      the test and clinical and radiological parameters were in concordance. The test
      was also crucial in diagnosing the onset of central precocious puberty in two
      children with congenital adrenal hyperplasia. CONCLUSION: GnRH agonist test is a
      convenient, safe test that can be performed on an out-patient basis and can help
      the clinicians in the correct diagnosis and appropriate treatment of various
      puberty-related disorders.

PMID- 22629508
TI  - Incidence of gall stone formation in acromegalic patients on octreotide therapy.
AB  - OBJECTIVE: Octreotide, a long-acting synthetic somatostatin analog, has been
      widely used for ac-romegalic patients. Gastrointestinal (GI) side effects and
      gall stones are predominant side effects. We report incidence of gall stones in
      our cohort of acromegalic patients treated with octreotide therapy. DESIGN:
      Retrospective case observational study. SETTING: Endocrinology Unit, Dr. Ram
      Manohar Lohia, Hospital, New Delhi. MATERIALS AND METHODS: Patients of acromegaly
      on primary or secondary octreotide therapy. INTERVENTION: Patients were enquired
      regarding complaints related to the GI system and their medical records were
      reviewed. Ultrasound films at various intervals while on octerotide therapy were
      evaluated by the radiologist for presence of sludge and development of gall
      stones. RESULTS: Of seven patients, five developed gallstones and sludge was seen
      in three patients at intervals ranging from 11 to 36 months postoctreotide
      initiation. CONCLUSION: A high incidence of gall stone formation in the present
      study as compared to the West was noted, the reasons for which are not clear.

PMID- 22629509
TI  - Vitamin D deficiency in newly diagnosed breast cancer patients.
AB  - AIM: The aim was to determine serum vitamin D levels in breast cancer patients
      and to assess its risk association with grade and stage of the tumor. MATERIALS
      AND METHODS: Ninety breast cancer patients and equal number of age-matched
      healthy females were recruited into the study by consecutive sampling over a
      period of 6 months for this case control study. Serum 25(OH)2D levels and CT bone
      mineral density was done. RESULTS: The mean age was 46+/-1.5 years. Age, marital
      status, menopausal, residential area, parda observing status, and body mass index
      were similar in distribution among cases and controls. The mean serum vitamin D
      level in the breast cancer patients was 9.3 ng/ml and in the control group was
      14.9 ng/ml (P value <0.001). Vitamin D deficiency was seen in 95.6% (86) breast
      cancer patients and in 77% (69) of the control group (P value <0.001). Among the
      breast cancer patients the tumor characteristics (histology, grade, stage, and
      receptor status) did not show any significant associations with serum levels of
      vitamin D. Premenopausal breast cancer females had a mean serum vitamin D level
      of 10.5 ng/ml and postmenopausal females had a mean value of 13.5 ng/ml (P value
      0.015). Low BMD did not correlate significantly with vitamin D deficiency (P
      value 0.787). CONCLUSION: Invariably almost all patients with breast cancer were
      vitamin D deficient. Tumor characteristics did not show any significant
      associations with serum levels of vitamin D. Bone mineral density did not
      correlate significantly with vitamin D deficiency.

PMID- 22629510
TI  - Pulmonary function tests in patients with primary hyperparathyroidism.
AB  - CONTEXT: There is limited information on respiratory muscle functions in patients
      with primary hyperparathyroidism (PHPT). AIM: To assess respiratory muscle
      dysfunction in patients with PHPT. SETTING AND DESIGN: This prospective study was
      carried between January 2005 and December 2006 by the Department of Endocrinology
      at the Postgraduate Institute of Medical Education and Research, Chandigarh.
      MATERIALS AND METHODS: PHPT was defined as elevated parathyroid hormone in the
      presence of hypercalcemia. Spirometry was performed using a dry rolling seal
      spirometer and spirometric indices like forced vital capacity (FVC), forced
      expiratory volume in first second (FEV(1)), and FEV(1)/FVC ratio were measured
      using standard guidelines. RESULTS: Thirty patients were studied with a mean age
      of 37.1 +/- 2.4 years and 18 were women. The most common presenting symptoms were
      fatigue (75.0%) and bone pain (60.70%). The mean (+/-SD) of percentage predicted
      FVE(1), FVC, FEV(1)/FVC ratio, PEF, and FEF were 98.7 +/- 16.1, 93.9 +/- 14.7,
      84.5 +/- 3.4, 89.3 +/- 22.5, and 99.7 +/- 33.6, respectively. Two had obstructive
      lung disease and two had restrictive lung disease. We did not find correlation
      with preoperative serum calcium, phosphate, and PTH with FVE(1), FVC, FEV(1)/FVC
      ratio, PEF, and FEF. CONCLUSION: Elevated calcium, low phosphate, and elevated
      PTH levels in patients with moderate to severe PHPT do not significantly affect
      respiratory muscle functions.

PMID- 22629511
TI  - The metabolic syndrome in thyroid disease: A report from Nigeria.
AB  - BACKGROUND: The objective of this study was to determine the prevalence of the
      metabolic syndrome and its components in people with thyroid disorders. MATERIALS
      AND METHODS: 112 subjects with a history of thyroid disorders were consecutively
      enrolled for the study. Clinical data were obtained by interviewing the patients
      and referring to their case folders and prescriptions. The subjects were
      categorized into three: thyrotoxic, those with hypothyroidism and those with
      nontoxic goiters, based on clinical parameters and or thyroid function tests. The
      study subjects were weighed and their anthropometric indices were documented. The
      laboratory parameters that were analyzed included total cholesterol, high-density
      and low-density cholesterol and triglyceride. Statistical analysis was performed
      using Student's t test, one-way analysis of variance (ANOVA) test and chi-square
      test. RESULTS: The study subjects were aged between 14 and 76 years, with a mean
      age of 44.5 years, and the female:male ratio was 97:15. The mean age and
      anthropometric indices were comparable in subjects with thyrotoxicosis,
      hypothyroidism and euthyroidism. The overall prevalence of the metabolic syndrome
      was 28% and the frequency of occurrence of the metabolic syndrome in subjects
      with thyrotoxicosis, hypothyroidism and nontoxic goiter was 24%, 40% and 42%,
      respectively. The commonest occurring metabolic syndrome defining criterion was
      dysglycemia, while hypertension and elevated triglyceride were the least
      documented of the criteria. CONCLUSION: Metabolic syndrome occurs in 1 in every 4
      persons with thyroid disorders, and as such, routine screening for this
      cardiovascular risk factor may be of benefit in this group of people, especially
      in those with hypothyroidism.

PMID- 22629512
TI  - Comprehensive yogic breathing program improves quality of life in patients with
      diabetes.
AB  - OBJECTIVE: To assess the effect of a comprehensive yogic breathing program on
      glycemic control and quality of life (QOL) in patients with diabetes. MATERIALS
      AND METHODS: This is a prospective randomized controlled intervention trial.
      Patients having HbA1c between 6 and 9% for at least 3 months with lifestyle
      modification and oral antidiabetic medication were included. They were followed
      up and randomized at 6 months into two groups: one group receiving standard
      treatment of diabetes and the other group receiving standard treatment of
      diabetes and taught and told to regularly practice the comprehensive yogic
      breathing program (Sudarshan Kriya Yoga and Pranayam). Change in fasting and post
      prandial blood sugars, glycated hemoglobin and QOL as assessed by the World
      Health Organization QOL WHOQOL BREF questionnaire were assessed. RESULTS: There
      was a trend toward improvement in glycemic control in the group practicing the
      comprehensive yogic breathing program compared with the group following standard
      treatment alone, although this was not significant. There was significant
      improvement in physical, psychological and social domains and total QOL post
      intervention in the group practicing the comprehensive yogic breathing program as
      compared with the group following standard treatment alone. CONCLUSION: There was
      significant improvement in the QOL and a non-significant trend toward improvement
      in glycemic control in the group practicing the comprehensive yogic breathing
      program compared with the group that was following standard treatment alone.

PMID- 22629513
TI  - The breasts of Tutankhamun.
AB  - Despite being an obscure pharaoh who ruled for a very short time, Tutankhamun,
      the boy king, has reigned popular consciousness since the discovery of his tomb
      in 1922. To endocrinologists, the depiction of the kings of the 18(th) dynasty in
      an androgynous form complete with gynecomastia has been a source of intrigue and
      academic curiosity. Many explanations abound. But is the depiction just stylized
      art? Or did the kings indeed have familial gynecomastia, or aromatase excess with
      craniosynostosis. An inspired team of researchers used molecular genetic tests to
      truly lay the Tut controversy to rest..

PMID- 22629514
TI  - Childhood adrenocortical carcinoma: Case report and review.
AB  - Adrenocortical cancers in childhood are very rare tumors. The tumors have varied
      presentation - either virilizing forms or presentation with Cushing's syndrome,
      or both. In children, due to the rapid development of symptoms they come to
      attention early, however, if not diagnosed and treated early can have a downhill
      course. The last decade has seen the emergence of new diagnostic imaging
      modalities. There is also intense ongoing research in newer treatment modalities
      as these tumors can be unresectable or have a high recurrence rate.

PMID- 22629515
TI  - Dysgerminoma in a female with turner syndrome and Y chromosome material: A case
      based review of literature.
AB  - We report a 17-year-old girl evaluated for primary amenorrhea. Cytogenetic
      analysis of the peripheral blood lymphocytes revealed normal autosomes with 46X
      inv (Y) confirming the diagnosis of Turner's syndrome with Y cell line. Treatment
      was initiated with conjugated estrogen while recommending bilateral prophylactic
      oophorectomy to the patient. One year later the patient presented with abdominal
      mass, biopsy of the specimen following resection confirmed dysgerminoma
      originating from right ovary with no invasion or metastasis. The literature is
      reviewed with regard to the various pathogenetic mechanisms proposed for the
      development of germ cell tumors in ovary, the cytogenetic findings and
      recommendations to handle such scenario.

PMID- 22629516
TI  - A rare case of lingual thyroid with hyperthyroidism: A case report and review of
      the literature.
AB  - Lingual thyroid is a rare embryological anomaly resulting from failure of normal
      thyroid tissue to descend from the foramen cecum at base of tongue to its
      orthotopic location in front of the lower neck. It is a rare anomaly with a
      reported incidence of 1 in 3000 of the thyroid disorders. Lingual thyroid is
      often asymptomatic but may cause local symptoms such as dysphagia, dysphonia with
      stomatolalia, upper airway obstruction, and often with hypothyroidism.
      Hyperthyroidism is extremely rare finding and till now there are very few case
      reports published. We present here a case of lingual thyroid with
      hyperthyroidism, which was treated successfully with radioiodine.

PMID- 22629517
TI  - Should neck pain in a patient with Hashimoto's thyroiditis be underestimated? A
      case and review of the literature.
AB  - Hashimoto's Thyroiditis (HT) is an autoimmune disease and the most frequent cause
      of hypothyroidism. Subacute thyroiditis (SAT) overlapping HT is a rare entity. A
      69-year-old female patient with HT and multinodular goiter has been followed on
      levothyroxine replacement therapy for 7 years. She presented with neck pain
      radiating to the right ear persisting for 2 months. She was prescribed analgesics
      and antibiotics by other physicians during that period, which did not work. Her
      vital signs were stable with no tachycardia or fever. The right lobe of the
      thyroid gland was tender on palpation. Her TSH level was 3.94 mIU/ml, ESR 23
      mm/h, CRP 3.2 mg/l, WBC 4900/MUl at presentation. Thyroid ultrasonography
      revealed a hypoechoic area over the tender lobe. Power Doppler imaging revealed
      almost no blood flow in that area. She was started on methylprednisolone 32
      mg/day. At day 10 of therapy, her symptoms had completely resolved.
      Ultrasonography repeated showed that the hypoechoic area had disappeared.
      Glucocorticoid dosage was tapered and stopped. Emergence of subacute thyroiditis
      in a case with preexisting Hashimoto's thyroiditis is a quite rare condition, but
      should be kept in mind along with a painful attack of HT in the differential
      diagnosis.

PMID- 22629518
TI  - Ogilvie's syndrome in a case of myxedema coma.
AB  - Ogilvie's syndrome [acute colonic pseudo-obstruction (ACPO)] presents as massive
      colonic dilatation without a mechanical cause, usually in critically ill patients
      due to imbalanced sympathetic and parasympathetic activity. The initial therapy
      remains conservative with supportive measures (correction of metabolic,
      infectious or pharmacologic factors) followed by neostigmine and decompressive
      colonoscopy. Surgery is reserved for patients with clinical deterioration or with
      evidence of colonic ischemia or perforation. A 60-year-old lady presented with
      fever, altered sensorium, obstipation, bradycardia and abdominal distension.
      Investigation revealed hyponatremia and acute colonic pseudo-obstruction.
      Supportive measures and decompressive colonoscopy were not of great benefit.
      Thyroid profile was suggestive of primary hypothyroidism. Colonic motility was
      restored only on starting thyroxin. The case is illustrative of the need to
      consider hypothyroidism, a common endocrine disorder, in the differential
      diagnosis of Ogilvie's.

PMID- 22629519
TI  - Osteonecrosis of jaw associated with bisphosphonate use.
AB  - Bisphosphonates are associated with osteonecrosis of the jaw (ONJ) that is
      defined as an area of exposed, nonvital bone in the maxilla or mandible
      persisting over 6-8 weeks. We describe a case of 55-year-old female who developed
      ONJ after tooth extraction and had been receiving oral ibandronate for
      osteoporosis. Diagnosis of ONJ was confirmed on CT scan. The patient was managed
      conservatively as she denied teriparatide therapy because of cost constraints.

PMID- 22629520
TI  - Short stature with umbilical hernia - Not always due to cretinism: A report of
      two cases.
AB  - A 7-year-old boy presented with umbilical hernia and short stature. Growth
      retardation, recurrent upper respiratory tract infections and delayed
      developmental milestones were present from infancy. Umbilical hernia was
      diagnosed at the age of 5 years. On examination, he had short-trunk dwarfism,
      large head circumference, coarse facial features, joint stiffness,
      hepatosplenomegaly, and mild mental retardation. He had normal biochemical
      parameters, thyroid function tests and arterial blood gas analysis. Radiological
      evaluation showed that the child had Hunter syndrome with findings of J-shaped
      sellaturcica, proximal bulleting of metacarpals, spatulated ribs and anterior
      beaking of lumbar vertebrae. The second case was a 6-year-old girl with umbilical
      hernia, short stature, normal biochemistry and radiological findings of
      mucopolysaccharidosis. However, she also had corneal opacity; confirmed by slit
      lamp examination, which led to the diagnosis of Hurler-Scheie syndrome. Enzymatic
      studies could not be done in both the cases, as they are not available at most
      centers.

PMID- 22629521
TI  - Acromegaly without acral changes: A rare presentation.
AB  - Acromegaly is diagnosed clinically by the universal presence of acral enlargement
      and typical coarse facies. We report a short, elderly female developing
      acromegalic facies for last 10 years without acral overgrowth. She is a patient
      of primary hypothyroidism, well controlled for last 20 years. Acromegaly was
      proven by high level of serum insulin like growth factor-1 (IGF-1) and elevated
      and nonsuppressed level of growth hormone (GH), with other hormonal profile being
      undisturbed. She had mild insulin resistance and systemic hypertension in absence
      of any visual field defect. Magnetic resonance imaging (MRI) of brain revealed
      pituitary hyperplasia without any detectable adenoma. No source of ectopic
      secretion of GH or growth hormone releasing hormone (GHRH) could be localized.
      Therefore, atypical presentation of acromegaly needs high degree of suspicion
      even if some of the common features are lacking. Here, we have biochemically
      proved acromegaly with typical facies, short stature but no acral overgrowth and
      pituitary adenoma despite longstanding disease activity, and thus eluding
      diagnosis for years.

PMID- 22629522
TI  - Dermopathy of Graves' disease: Clinico-pathological correlation.
AB  - Dermopathy of Graves' disease is a classical, but uncommon extrathyroidal
      manifestation of Graves' disease. The images of a typical case of dermopathy of
      Graves' disease are presented along with clinico-pathological correlation.

PMID- 22629523
TI  - Vitiligo, hypothyroidism and cardiomyopathy.
AB  - Vitiligo in association with autoimmune endocrine disorders, especially with
      hypothyroidism, is not uncommon. Some amount of pericardial effusion is usually
      present in long-standing/untreated hypothyroidism. Here we describe the case of
      young male with, long-standing progressive vitiligo, presenting with congestive
      cardiac failure due to dilated cardiomyopathy and primary hypothyroidism. Cardiac
      dysfunction progressively improved with thyroid hormone replacement over a period
      of 2 years.

PMID- 22629524
TI  - A curious case of refractory hypothyroidism due to selective malabsorption of
      oral thyroxine.
AB  - There are very few cases in the literature in which refractory persistent
      hypothyroidism responded only to parenteral doses of levothyroxine and no
      evidence of any malabsorptive disorder could be identified. Here, we present a
      rare case of a 35-year-old woman with refractory hypothyroidism who responded
      only to intravenous doses of levothyroxine. We also discuss possible causes for
      the same.

PMID- 22629525
TI  - Large but benign adrenal mass: Adrenal oncocytoma.
AB  - Adrenal incidentalomas of more than 4 cm size are usually malignant. We describe
      a 28-year-old woman with a 7-cm, non-functioning, well-demarcated adrenal mass,
      which was identified as an oncocytoma on histopathological examination.
      Therefore, a large, non-functioning, unilateral adrenal mass with preserved tumor
      outline should invoke the suspicion of oncocytoma, which is invariably a benign
      tumor.

PMID- 22629526
TI  - Type 2 DM is not coronary artery disease equivalent.

PMID- 22629527
TI  - Authors' reply.

PMID- 22629528
TI  - Hypoglycemia and myocardial infarction: Inhibition of ischemic preconditioning
      response.

PMID- 22629529
TI  - Injection site lipodystrophy and the endocrinologist.

PMID- 22629530
TI  - Waist circumference cutoff and metabolic syndrome.

PMID- 22629531
TI  - Panhypopituitarism presenting as azoospermia.

PMID- 22629532
TI  - Stunning in post (131)I therapy scans after low-dose (131)I diagnostic whole body
      scans with differentiated thyroid cancer in the Indian patient population:
      Critical importance of interval between the two scans.

PMID- 22629533
TI  - Pancytopenia with cellular bone marrow related to Graves' hyperthyroidism.

PMID- 22629534
TI  - A rare case of autoimmune polyglandular syndrome type IIIc.

PMID- 22629535
TI  - Unassisted successful pregnancy in a case of Addison's disease with recurrent
      pregnancy loss.

PMID- 22629536
TI  - A tale of nonhormonal hairs.

PMID- 22629537
TI  - Hyperandrogenemia due to ingestion of Butea superba.

PMID- 22629538
TI  - A rare case of Mauriac syndrome.

PMID- 22629539
TI  - Images in endocrinology: Archibald's metacarpal sign.

PMID- 22629540
TI  - Ocular tissue responses to sex hormones.

PMID- 22629541
TI  - Do we need sick-day guidelines for hypoparathyroidism?

PMID- 22629543
TI  - [Morphological and immunophenotypical heterogeneity in breast cancers of young
      and elderly women].
AB  - There is a reasonable heterogeneity in the morphological appearance and the
      immunohistochemical properties of distinct breast tumors. Furthermore, it is also
      known that cancer arising in young women have different prognosis than the ones
      developing in the elderly. We analyzed breast tumors of 41 young (<35 years) and
      33 older women (>65 years) regarding histopathological properties and
      immunohistochemical reactions for ER, PgR, HER2 and Ki-67, as well as HER2 FISH.
      The longest diameters, thus largest available surface areas of the tumors were
      included in the evaluation. Different regions were marked for morphology and in
      all immunohistochemical reactions. The regions in the distinct tumors showing
      different pathological and immunohistochemical appearance were identical
      (p<0.001). The number of morphologically different tumor regions were more
      frequent in tumors developing in the young (1.82 vs. 1.48 regions/tumor), and
      53.6% of tumors with heterogeneous architecture were in young vs. 39.4% in the
      elderly. However, regarding HER2 staining, cancers in the young patients have
      shown greater variability among the different tumor areas (p=0.007). The origin
      of tumor cells predicting prognosis remains undetermined. Whether the analysis of
      the expression pattern of the whole tumor is conducted or the minute regions are
      separately examined and averaged, the same results can be achieved. With the
      development of molecular techniques and accurate prognostic and treatment
      information rendered to samples the question may be soon answered.

PMID- 22629542
TI  - [Second breast-conserving surgery and reirradiation with interstitial high-dose
      rate brachytherapy for the management of intra-breast recurrences -- 5-year
      results].
AB  - The purpose of our work was to evaluate the efficacy of second breast-conserving
      surgery (BCS) and reirradiation with interstitial high-dose-rate (HDR)
      brachytherapy (BT) for the management of local recurrences. Between 1999 and
      2010, fifteen patients initially treated for breast carcinoma by BCS and
      radiation therapy who had isolated intra-breast recurrence underwent second BCS
      and perioperative HDR multicatheter BT. Breast cancer related events, late side
      effects, and cosmetic results were assessed. At a median follow-up of 62 months
      (range: 11-127) second local recurrence has not occurred, yielding a 100%
      mastectomy-free survival. Four patients (27%) developed subsequent distant
      metastasis and died of breast cancer. The 5-year actuarial rate of disease-free
      and overall survival was 69% and 85%, respectively. Cosmetic results were rated
      excellent, good, fair, poor, and unknown in 1 (7%), 10 (66%), 2 (13%), 1 (7%),
      and 1 (7%) patients, respectively. Grade 2 fibrosis and skin toxicity occurred in
      1 (7%) and 1 (7%) patients. Asymptomatic fat necrosis was detected in 9 (60%)
      women. No patient developed grade 3-4 late side effects. Second BCS followed by
      partial breast reirradiation is a safe and effective option for the management of
      selected patients developing intra-breast recurrence after previous breast
      conserving therapy. Perioperative HDR BT may decrease the risk of second local
      relapse with acceptable cosmetic results and low rate of late side effects.

PMID- 22629544
TI  - [Diagnostic imaging and histologic background of nipple discharge -- our
      experience with 40 patients].
AB  - The authors present the diverse etiology of nipple discharge, which background
      may be a tumor. They discuss the checkup ways of nipple discharge and review in
      detail the galactographic technique and evaluation. The examination of pathologic
      nipple discharge is essentially based on contact cytology, x-ray-, and ultrasound
      mammography. Consequently, galactography is applied by filling the ducts with
      contrast material. The final diagnosis is rendered by histologic examination,
      following the operation. The authors demonstrate the application and role of
      galactography through various cases.

PMID- 22629545
TI  - [The role of PET-CT in detecting unknown primary tumour in patients with cervical
      lymph node metastases].
AB  - PET-CT examination was conducted with 440 patients treated at the Department of
      Head and Neck Surgery, National Institute of Oncology, Budapest, between January
      1, 2006 and December 31, 2010. Out of them 77 patients were selected with whom no
      examination of any sort (physical, pan-endoscopy, or any of the conventional
      imaging techniques) succeeded in identifying the primary tumour. In each case the
      primary examination (aspiration cytology and histology) verified cervical
      metastases, most of them being squamous cell carcinoma. The significance of PET
      CT was retrospectively evaluated in cases of unknown primary tumour with verified
      cervical metastases. We tested the sensitivity of PET-CT in detection of the
      primary malignant tumour, and possible distant metastases or a second primary in
      order to plan an optimal treatment schedule for the patient. Patients with whom
      the examinations specified in the treatment protocol (physical examination, pan
      endoscopy, conventional imaging, biopsy) had failed to diagnose the primary
      tumour were referred to PET-CT. In each case 18F-FDG tracer was used. In 21/77
      patients (27%), the PET-CT yielded unequivocal evidence for the primary tumour
      confirmed by histology, as well. With 10 others (13%), the precarious diagnoses
      by various imaging techniques were confirmed by the PET-CT. False positive
      findings with PET-CT that were not verified either by histology or control
      examination tests occurred but in 10 patients (13%). Concerning the primary
      tumour, false negative result was obtained only with 3 patients (4%). It should
      be noted that their retrospective evaluation proved diagnostic errors, the
      primary tumours were visible in all the scans. With 33 patients (43%) PET-CT
      furnished no additional information compared to the previous examinations. In 10
      patients, asymptomatic distant metastases and in 3 patients synchronous tumours
      were diagnosed. We also acknowledge that the significance of PET-CT using 18F-FDG
      is unquestionable in the detection of unknown primary tumours. It is strongly
      recommended to re-include the detection of unknown primaries in the approved
      national indication list of PET-CT. (Note, until January 1, 2008 it had been
      included!) PET-CT is capable of detecting a primary tumour, after all
      unsuccessful diagnostic examinations till then, in 25-40% of the cases. One
      cannot disregard the role and significance of PET-CT in the detection of
      asymptomatic synchronous tumours, or distant metastases. These benefits make PET
      CT a suitable tool for the refinement of individually tailored treatment
      strategies leading to better therapeutic results and more favourable cost-benefit
      ratio.

PMID- 22629546
TI  - [Need for developing a new strategy in the follow-up of colorectal cancer
      patients; the micro RNAs (miRNAs), as potential new biomarkers of early
      detection].
AB  - In the mortality statistics of European countries colorectal cancers are known to
      assume the 2nd place after lung cancer. The mortality indices are particularly
      unfavourable in Hungary. Early detection is therefore of vital importance to the
      patient either the detection of the primary or recurrence after successful
      surgery is concerned. The latter is only feasible within a proper follow-up
      strategy. The present review focuses on follow-up due after surgical removal of
      the tumour with special emphasis on the efficacy of a new biomarker group
      (miRNAs) and their potential combination with the traditional markers. It is a
      model in the follow-up strategy that considers the results of risk assessment, as
      well. Since the methodology and strategy of follow-up are still controversial
      matters it is obvious that the development of a new follow-up strategy is
      imperative.

PMID- 22629547
TI  - [Clinical pharmacology aspects of development and application of biosimilar
      antibodies].
AB  - Due to the microheterogeneity of the macromolecules produced in biological
      systems, only the high degree of similarity but not the structural identity of
      the follow-on biological active agents can be proven. In case of monoclonal
      antibodies (mAbs) the proof of similarity is much more difficult due to the large
      molecular weight, complicated structure and complex biological effects of the IgG
      molecule. The identity of the amino acid sequence is the basic requirement of
      biosimilarity. Smaller changes in the carbohydrate side chains attached to the
      protein molecule can be accepted if they do not cause significant functional
      changes. On the other hand, the alteration of some carbohydrate side chain(s)
      located at strategically important sites might significantly influence the
      biological properties of the mAbs. Besides the antigen binding the
      pharmacological effects of the antibodies depend on several other effector
      functions related to the Fc fragment such as antibody-dependent cell-mediated
      cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and phagocytosis.
      Hence several biological functions must be measured and evaluated in their
      totality for stating the degree of biosimilarity. According to the concordant
      strict requirements of the European Medicines Agency (EMA) and the American Food
      and Drug Administration (FDA), the proof of similar efficacy and safety must be
      based on the results obtained in the most sensitive and suitable in vitro and in
      vivo experimental designs. The fundamental proofs are provided by the comparison
      of the pharmacokinetic and pharmacodynamic measurements, as well as the
      similarity of the dose-effect relationships. These observations are complemented
      by the comparative clinical therapeutic trials which eventually support the
      similar therapeutic use of the follow-on medicinal products in the clinical
      practice. The final judgement of biosimilarity is a case-by-case decision based
      on the joint evaluation of all the data available.

PMID- 22629548
TI  - The drugs can work.
AB  - There are signs that the therapeutic successes that have contributed to the
      downward trajectory for HIV-1 mortality may soon be repeated for HCV.

PMID- 22629549
TI  - Abstracts of Europerio 7. June 6-9, 2012. Vienna, Austria.

PMID- 22629550
TI  - Abstracts of the British Cardiovascular Society Annual Conference. May 28-30,
      2012. Manchester, United Kingdom.

PMID- 22629551
TI  - [Zinc supplements and pneumonia in children].

PMID- 22629552
TI  - Increased prevalence of light chain monoclonal gammopathy of undetermined
      significance (LC-MGUS) in first-degree relatives of individuals with multiple
      myeloma.
AB  - Previously, we reported increased risk of heavy-chain (HC) monoclonal gammopathy
      of undetermined significance (MGUS) among first-degree (1 degrees ) relatives of
      multiple myeloma (MM) or HC-MGUS probands. This study investigated whether there
      was comparable risk for light-chain (LC) MGUS among 911 relatives of the same HC
      MGUS/MM probands versus a reference population of 21 463. Seventeen 1 degrees 
      relatives had LC-MGUS (adjusted prevalence = 1.7%, 95% CI = 0.9-2.6%). There was
      increased risk of LC-MGUS in relatives of MM probands (RR = 3.4, 95% CI = 2.0
      5.5). We saw no increased risk in relatives of HC-MGUS probands. We conclude that
      the prevalence of LC-MGUS is significantly higher among 1 degrees  relatives of
      MM probands compared to the reference population.

PMID- 22629553
TI  - Strengthening research partnerships for better health and sustainable
      development. Abstracts of the Sixth EDCTP (European and Developing Countries
      Clinical Trials Partnership) Forum. October 9-12, 2011. Addis Ababa, Ethiopia.

PMID- 22629554
TI  - Erratum. Wang ZQ, Yu Y, Zhang XH, Ribnicky D, and Cefalu WT. Ecdysterone enhances
      muscle insulin signaling by modulating acylcarnitine profile and mitochondrial
      oxidative phosphorylation complexes in mice fed a high-fat diet. Diabetes DOI:
      10.2337/db10-1605.

PMID- 22629555
TI  - The value of human being.

PMID- 22629556
TI  - Abstracts of the Australasian College of Dermatologists 45th Annual Scientific
      Meeting. May 20-23, 2012. Brisbane, Queensland, Australia.

PMID- 22629557
TI  - Abstracts of ECTS (European Calcified Tissue Society) 2012, 39th Annual Congress.
      Stockholm, Sweden. May 19-23, 2012.

PMID- 22629558
TI  - Proceedings of the 18th International Symposium on Electro-and Liquid Phase
      Separation Techniques, August 28-31, 2011, Tbilisi, Georgia.

PMID- 22629559
TI  - Proceedings of the IOC Consensus Conference on Nutrition in Sport, 25-27 October
      2010, Lausanne, Switzerland.

PMID- 22629560
TI  - Abstracts of the 2012 World Congress on In Vitro Biology. June 3-7, 2012.
      Bellevue, Washington, USA.

PMID- 22629561
TI  - [Pregnancy following bariatric surgery requires special attention].

PMID- 22629562
TI  - [Tourette syndrome].

PMID- 22629563
TI  - Abstracts of the 49th ERA-EDTA (European Renal Association - European Dialysis
      and Transplant Association) Congress. May 24-27, 2012. Paris, France.

PMID- 22629564
TI  - Proceedings of the Joint RECOMB Conference on Systems Biology, Regulatory
      Genomics, and DREAM Challenges, October 14-19, 2011, Barcelona, Spain.

PMID- 22629565
TI  - Postgraduate options: Academia misses the mark.

PMID- 22629566
TI  - Active surrender.

PMID- 22629567
TI  - Therapy resistance by splicing: can the androgen receptor teach us about BRAF?

PMID- 22629568
TI  - Pigmentation or transparency? Camouflage tactics in deep-sea cephalopods.

PMID- 22629569
TI  - Immunoediting the cancer genome--a new approach for personalized cancer therapy?

PMID- 22629570
TI  - Methods and applications for assembling large DNA constructs.
AB  - The construction of large DNA molecules that encode pathways, biological
      machinery, and entire genomes has been limited to the reproduction of natural
      sequences. However, now that robust methods for assembling hundreds of DNA
      fragments into constructs > 20 kb are readily available, optimization of large
      genetic elements for metabolic engineering purposes is becoming more routine.
      Here, various DNA assembly methodologies are reviewed and some of their potential
      applications are discussed. We tested the potential of DNA assembly to install
      rational changes in complex biosynthetic pathways, their potential for generating
      complex libraries, and consider how various strategies are applicable to
      metabolic engineering.

PMID- 22629571
TI  - The future of metabolic engineering and synthetic biology: towards a systematic
      practice.
AB  - Industrial biotechnology promises to revolutionize conventional chemical
      manufacturing in the years ahead, largely owing to the excellent progress in our
      ability to re-engineer cellular metabolism. However, most successes of metabolic
      engineering have been confined to over-producing natively synthesized metabolites
      in E. coli and S. cerevisiae. A major reason for this development has been the
      descent of metabolic engineering, particularly secondary metabolic engineering,
      to a collection of demonstrations rather than a systematic practice with
      generalizable tools. Synthetic biology, a more recent development, faces similar
      criticisms. Herein, we attempt to lay down a framework around which bioreaction
      engineering can systematize itself just like chemical reaction engineering.
      Central to this undertaking is a new approach to engineering secondary metabolism
      known as 'multivariate modular metabolic engineering' (MMME), whose novelty lies
      in its assessment and elimination of regulatory and pathway bottlenecks by re
      defining the metabolic network as a collection of distinct modules. After
      introducing the core principles of MMME, we shall then present a number of recent
      developments in secondary metabolic engineering that could potentially serve as
      its facilitators. It is hoped that the ever-declining costs of de novo gene
      synthesis; the improved use of bioinformatic tools to mine, sort and analyze
      biological data; and the increasing sensitivity and sophistication of
      investigational tools will make the maturation of microbial metabolic engineering
      an autocatalytic process. Encouraged by these advances, research groups across
      the world would take up the challenge of secondary metabolite production in
      simple hosts with renewed vigor, thereby adding to the range of products
      synthesized using metabolic engineering.

PMID- 22629573
TI  - [Attach great importance to drug-induced liver injury: from bench to bedside].

PMID- 22629572
TI  - Computational tools for metabolic engineering.
AB  - A great variety of software applications are now employed in the metabolic
      engineering field. These applications have been created to support a wide range
      of experimental and analysis techniques. Computational tools are utilized
      throughout the metabolic engineering workflow to extract and interpret relevant
      information from large data sets, to present complex models in a more manageable
      form, and to propose efficient network design strategies. In this review, we
      present a number of tools that can assist in modifying and understanding cellular
      metabolic networks. The review covers seven areas of relevance to metabolic
      engineers. These include metabolic reconstruction efforts, network visualization,
      nucleic acid and protein engineering, metabolic flux analysis, pathway
      prospecting, post-structural network analysis and culture optimization. The list
      of available tools is extensive and we can only highlight a small, representative
      portion of the tools from each area.

PMID- 22629575
TI  - [Clinical diagnostic methods and evaluation of drug-induced liver injury].

PMID- 22629574
TI  - [Mechanisms of drug-induced liver injury].

PMID- 22629576
TI  - [The diagnosis and treatment of drug-induced liver injury].

PMID- 22629577
TI  - [Chinese herb and drug-induced liver injury].

PMID- 22629578
TI  - Unresectable colorectal cancer liver metastases treated by intraoperative
      radiofrequency ablation with or without resection (Br J Surg 2012; 99: 558-565).

PMID- 22629579
TI  - [Discussion on pathological scoring system of drug-induced liver injury].

PMID- 22629580
TI  - [Cognition and perplexity on adaptation and tolerance of drug-induced liver
      injury].

PMID- 22629581
TI  - [Rational use of antibiotics in patients with hepatic dysfunction].

PMID- 22629582
TI  - [A case of anti-HCV treatment in cirrhosis patient with vitiligo].

PMID- 22629583
TI  - [Interferon a-2b treatment of chronic hepatitis C caused by white-haired one
      case].

PMID- 22629584
TI  - [Signaling pathways in activated hepatic stellate cells].

PMID- 22629586
TI  - [Optimization approach to arterial hemodynamics on the systole stage].
AB  - With the help of a simple model of arterial hemodynamics as an example, the
      authors demonstrate it that dynamics of arterial pressure including the top and
      lower pressure values, systole-diastole length ratio, and coefficients of
      arterial and capillary elasticity can be obtained as an optimal solution of the
      problem of maintaining appropriate intensity of oxygen ingress in body tissues
      despite minimal "physiological" ability of the heart.

PMID- 22629585
TI  - [Methods of extending the resource of fiber ionite artificial soils in space
      greenhouses].
AB  - The vegetable cultivation technology developed in view of long-term autonomous
      missions is based on root nutrition provided by fiber artificial soils (AS)
      containing ion-exchange resins. Useful life of ASs is limited by two factors
      which are nutrients depletion in ion-exchanger and clogging of the AS threshold
      space by roots remnants. Purpose of the investigation is to try out hydrolysis
      and ensuing microbial decomposition of roots remnants as a way to extend the
      resource of used fiber ionite AS. This principle of doing away with the roots
      remnants recovers almost completely the maximal water-absorbing capacity of AS
      BIONA-V3 so that it can be used again for crops cultivation.

PMID- 22629587
TI  - [Microbial fuel cells as an alternative power supply].
AB  - Purpose of the work was designing and prototyping of microbial fuel cells (MFC)
      and comparative evaluation of the electrogenic activity of wastewater
      autochthonous microorganisms as well as bacterial monocultures. Objects were
      model electrogenic strain Shewanella oneidensis MR-1, and an Ochrobactrum sp.
      strain isolated from the active anode biofilm of MFC composed as an electricity
      generating system. The study employed the methods typically used for aerobic and
      anaerobic strains, current measurement, identification of new electrogenic
      strains in microbial association of wastewater sludge and species definition by
      rRNA 16-S. As a result, two MFCs prototypes were tried out. Besides, it was shown
      that electrogenic activity of S. oneidensis MR-1 and Ochrobactrum sp.
      monocultures is similar but differs from that of the microbial association of the
      anode biofilm.

PMID- 22629588
TI  - [Motivation and professional activity].

PMID- 22629590
TI  - Quality, innovation, prevention and productivity.

PMID- 22629591
TI  - Reducing needlestick injuries: a review of a community service.
AB  - Community nurses provide care to patients in a variety of settings; for example,
      health centres, community hospitals, patients' homes, and residential and nursing
      homes. Administering intramuscular (IM)injections to patients in the community is
      an everyday activity for many nurses in clinical practice. A great deal of
      problems related to being 'sharps safe' are common to both community nurses and
      hospital staff. There had been a reported six needlestick injuries (NSIs) from
      community clinics administering depot IM injections, which required a review. An
      audit of practice was undertaken in clinics administering depot injections. The
      audit was undertaken to monitor compliance in sharps management and investigated
      how community nurses were administering IM injections. The review highlighted a
      lack of resources, gaps in knowledge and training deficits. The infection
      prevention and control nurses worked hard to improve practices and procedures.
      After a year, there had been a significant reduction in NSIs.

PMID- 22629592
TI  - Analysis of infusion pump error logs and their significance for health care.
AB  - Infusion therapy is one of the largest practised therapies in any healthcare
      organisation, and infusion pumps are used to deliver millions of infusions every
      year in the NHS. The aircraft industry downloads information from 'black boxes'
      to help design better systems and reduce risk; however, the same cannot be said
      about error logs and data logs from infusion pumps. This study downloaded and
      analysed approximately 360 000 hours of infusion pump error logs from 131
      infusion pumps used for up to 2 years in one large acute hospital. Staff had to
      manage 260 129 alarms; this accounted for approximately 5% of total infusion
      time, costing about L1000 per pump per year. This paper describes many such
      insights, including numerous technical errors, propensity for certain alarms in
      clinical conditions, logistical issues and how infrastructure problems can lead
      to an increase in alarm conditions. Routine use of error log analysis, combined
      with appropriate management of pumps to help identify improved device design, use
      and application is recommended.

PMID- 22629593
TI  - A comparison between intravenous and subcutmaneous immunogobulin.
AB  - Multifocal motor neuropathy (MMN) is a rare immune-mediated disease that presents
      with predominantly distal motor weakness in one or more limbs without sensory
      loss. Symptoms may give riseto functional impairment and consequently may affect
      quality of life. High-dose intravenous immunoglobulin's therapy (IVIg) is the
      current mainstay treatment, however, subcutaneous immunoglobuli(SCIg) is emerging
      as a viable alternative. The purpose of this study was to explore the patients'
      experience of SCIg and ascertain if those receiving it had an improved quality of
      life and treatmentsatisfaction compared to those receiving IVIg. Using a mixed
      method approach this paper will present its findings and key implications for
      clinical and research practice are considered. The results from this study
      suggest that home SCIg therapy may prove a more desirable treatment option than
      IVIg for a proportion of MMN patients.

PMID- 22629594
TI  - An algorithm for the use of intravenous salbutamol in children.

PMID- 22629595
TI  - [Ethics for being a radiological technologist and/or a researcher].

PMID- 22629596
TI  - Making abortion services accessible in the wake of legal reforms.
AB  - The passage of a liberalized abortion law is one of many changes that must take
      place if women are to gain access to safe and legal services. A study of the
      process following legal reforms in six settings in Asia, Africa and Latin America
      confirms that the practical work of establishing safe abortion services can take
      years and requires resources and commitment. Where these efforts have been
      undertaken and information on trends in abortion-related illness and death is
      available, evidence is beginning to demonstrate that liberalized laws are
      followed by improved health outcomes for women.

PMID- 22629597
TI  - Overweight and obesity in Massachusetts: a focus on physical activity.

PMID- 22629598
TI  - [The dissolution test in biorelevant media as a prognostic tool for modeling of
      drug behavior in vivo].
AB  - The review deals with the modern tool for modeling of drug behavior in vivo, -
      the dissolution test in biorelevant media, imitating gastrointestinal fluids. The
      formulations and preparation methods of fasted state simulation intestinal fluid,
      FaSSIF and fed state simulation intestinal fluid, FeSSIF, are defined. In
      addition, the dissolution characteristics of APIs from different BCS classes in
      biorelevant media are described. Possible applications of biorelevant media in
      regulatory practice and science are also shown.

PMID- 22629599
TI  - [The influence of mildronate on peripheral neuropathy and some characteristics of
      glucose and lipid metabolism in rat streptozotocin-induced diabetes mellitus
      model].
AB  - Streptozotocin (STZ) was used to induce the diabetic rat model. STZ rats were
      treated with mildronate (100 mg/kg daily, per os or intraperitoneally for 6
      weeks). Body weight, blood glucose, triglyceride, ketone body concentrations,
      glycated hemoglobin percent (HbA1c%), glucose tolerance, and the development of
      neuropathic pain were monitored throughout the experiment. In the STZ +
      mildronate group, mildronate treatment caused a significant decrease in mean
      blood glucose (on week 4) and triglyceride concentrations (on weeks 3-6),
      significantly slowed the increase in HbA1c% (on week 6) and improved glucose
      tolerance 120 minutes after glucose ingestion during oral glucose tolerance test
      versus the STZ group. Mildronate completely protected development of STZ-induced
      neuropathic pain from the first administration week up to end of the experiment.
      The obtained data indicate clinical usefulness of the drug for the treatment of
      diabetes mellitus and its complications.

PMID- 22629600
TI  - [The influence of compound aITEL1296 on telomerase activity and the growth of
      cancer cells].
AB  - Telomerase is a ribonucleoprotein that synthesizes telomeric repeats and
      identified as a promising target for anticancer therapy. Here we describe a new
      compound aITEL1296 as a potent telomerase inhibitor. Its inhibitory activity was
      a bit higher (IC50 = 0,19 +/- 0,02 ng/ml) than that of BIBR1532, one of the most
      potent telomerase inhibitors known to date. Besides telomerase inhibition
      aITEL1296 activated apoptotic mechanisms and effectively suppressed proliferation
      of tumor cell lines (GI50 = 5,0 +/- 0,2 ng/ml for most sensitive cell line LnCap)
      but not normal fibroblast cell line.

PMID- 22629601
TI  - [Lysozyme activity of the salivary gland secretion of the medicinal leech H.
      verbana, H. medicinalis and H. orientalis].
AB  - Salivary gland secretions of three species of the medicinal leech differ in the
      level of lysozyme peptidoglycan-lysing activity. Using the synthetic fluorogenic
      substrate, 4-methyl-umbelliferyl tetra N-acetyl-beta-chitotetraosid, the
      glycosidase activity (as one of peptidoglycan-lysing activities) of salivary
      gland secretion of three species of the medicinal leech was quantitatively
      evaluated in comparison with egg lysozyme. It is supposed, that lysozyme activity
      of the leech secretions is determined not only by 5 isoforms of destabilase
      lysozyme, but by some other enzymes which can utilize this substrate. These may
      be lysozymes other than i- (invertebrate) lysozymes (such as destabilase
      lysozyme, or related enzymes).

PMID- 22629602
TI  - [The influence of N-[imino(1-piperidinyl)methyl]guanidine and N-[imino(4
      morpholinyl)methyl]guanidine on citrate content, aconitase and citrate synthase
      activities at ischemia-reperfusion of rats brain].
AB  - The influence of some guanidine derivatives on the level of brain citrate, brain
      activities of aconitase and citrate synthase has been investigated in rats
      subjected to ischemia-reperfusion. Administration of N-[imino(1
      piperidinyl)methyl]guanidine and N-[imino(4-morpholinyl)methyl]guanidine resulted
      in changes of specific activities of aconitase and citrate synthase towards
      control values. Under these conditions the citrate level considerably decreased
      versus rats with untreated ishemia-reperfusion. Treatment with these compounds
      also decreased the degree of DNA fragmentation markedly increased in rats with
      ischemia-reperfusion.

PMID- 22629603
TI  - [Some inhibitors of purine nucleoside phosphorylase].
AB  - Purine nucleoside phosphorylase (PNP) catalyzes reversible phosphorolysis of
      purine deoxy- and ribonucleosides with formation (d)Rib-1-P and corresponding
      bases. PNP plays a leading role in the cell metabolism of nucleosides and
      nucleotides, as well as in maintaining the immune status of an organism. The
      major aim of the majority of studies on the PNP is the detection of highly
      effective inhibitors of this enzyme, derivatives ofpurine nucleosides used in
      medicine as immunosuppressors, which are essential for creating selective T-cell
      immunodeficiency in a human body for organ and tissue transplantation. The
      present work is devoted to the study of the effects of some synthetic derivatives
      of purine nucleosides on activity of highly purified PNP from rabbit spleen and
      also from human healthy and tumor tissues of lung and kidneys. Purine nucleoside
      analogues modified at various positions of both the heterocyclic base and
      carbohydrate residues have been investigated. Several compounds, including 8
      mercapto-acyclovir, 8-bromo-9-(3,4-hydroxy-butyl)guanine, which demonstrated
      potent PNP inhibition, could be offered for subsequent study as immunosuppressors
      during organ and tissue transplantation.

PMID- 22629604
TI  - [The cultivation of bone marrow cells and cell lines on polymeric films].
AB  - The cultivation of multipotent mesenchymal stromal bone marrow cells and cells of
      A-431, MDCK, Vero, 3T3 and Hep-G2 was performed on polymeric films (PVA) with
      different hydrophobic fatty acid residues. The cells of different types grew on
      these films with different intensity, but in the most cases comparable with the
      cultivation control on usual plastic. The examined films were nontoxic to cells
      and sufficiently adhesive. They did not changed pH of cultural media, were
      optically transparent under microscope and comfortable in the experimental work.
      These films can be used as a model for the artificial organ construction. The
      covalent binding of different fatty acids to PVA shows possibility of the
      adaptable changes of films properties (hydrophobity and adhesiveness), and
      therefore possibility of the creation of optimal conditions for different cell
      types attachement and growth.

PMID- 22629605
TI  - [Phenothiazines are slowly oxidizable substrates of horseradish peroxidase].
AB  - Reactions of peroxidase oxidation of triftazine and thioproperazine have been
      investigated in the presence of horseradish peroxidase using steady state kinetic
      methods. It has been shown that phenothiazines are slowly oxidizable substrates
      for horseradish peroxidase. k(cat) and K(m) values have been determined in the
      range of pH from 4.5 to 7.5. The study of co-oxidation of phenothiazines and o
      dianisidine (ODN) revealed that in the presence of aminazine and ODN in the
      reaction medium both substances follow sequential oxidation. ODN oxidation was
      not observed until full conversion of aminazine. At pH 4.5-5.5 thioproperazine
      bound to the enzyme-substrate complex and caused a nticompetitive inhibition of
      peroxidase. At pH>5.5 sequential substrate oxidation with preferential
      thioproperazine conversion occurred. In the range of pH from 4.5 to 7.5
      triftazine did not influence ODN oxidation.

PMID- 22629606
TI  - [Enzyme-linked immunosorbent assay for determination of cyclosporin A in whole
      blood].
AB  - A test-system based on enzyme-linked immunosorbent assay (ELISA) for quantitative
      determination of cyclosporin A (CSA) in human whole blood has been developed. The
      detection limit of the method was 25 ng/ml, the linearity of the method in the
      concentration range 60-1400 ng/ml varied from 94 to 105%, the variation
      coefficient did not exceed 8%. The novel method exhibited good correlation with
      radio-immunoassay and polarization fluoroimmunoassay methods; the linear
      regression coefficients were 0.965 and 0.983, respectively. The developed test
      system is stable for at least 9 months when stored at 4 degrees C and can be used
      in clinical practice.

PMID- 22629607
TI  - [Catecholamines and their metabolites in children with Asperger and Kanner
      syndromes].
AB  - Children with Asperger and Kanner syndromes in the stable state demonstrate
      similar decrease in plasma norepinephrine. In the aggravated state, these changes
      become more expressed and are characterized by a decrease in plasma tyrosine,
      norepinephrine, normetanephrine and by an increase in dopamine and homovanylic
      acid and a decrease in excretion of norepinephrine and an increase in excretion
      of homovanylic acid, epinephrine and MHPG. Only in children with Kanner syndrome
      in the aggravated state plasma MHPG increases, excretion of tyrosine decreases
      and excretion of normetanephrine increases. The observed imbalance in dopamine
      and epinephrine/norepinephrine systems justifies combined analysis of changes in
      catecholamines and their metabolites levels as the most informative approach in
      the study of the effect of autistic disorders.

PMID- 22629608
TI  - [Changes in the fatty acid composition of blood cell membranes in children with
      inflammatory diseases].
AB  - Fatty acid composition of erythrocyte and leukocyte membranes has been studied in
      children (with normal body mass and obesity) with inflammatory diseases of the
      gastrointestinal tract and children with bronchial asthma in comparison with
      basically healthy children. Fifty seven children aged from 7 to 14 years were
      examined: 13 with inflammatory diseases of the gastrointestinal tract (IDGIT)
      (eosophagitis, gastroduodenitis, stomach ulcer), 25 with obesity stages (I-III)
      complicated by IDGIT, 9 with bronchial asthma and 10 basically healthy children.
      The study revealed that both IDGIT and bronchial asthma caused significant and
      similar changes in fatty acid composition of cell membranes. These included
      accumulation of omega3-eicosapentaenoic acid (EPA) and the decrease of
      docosahexaenoic acid (DHA); this phenomenon observed in both erythrocyte and
      leukocyte membranes suggests a common feature of the detected changes in fatty
      acid composition of cell membranes in inflammation. There was a significant
      decrease in the level of membrane omega6 polyunsaturated fatty acids (PUFA),
      first of all arachidonic acid and total omega6 PUFA. Consequently, EPA
      accumulation in membranes may be a compensatory response to low dietary
      arachidonic acid supply and/or its increased synthesis of pro-inflammatory
      eicosanoids (prostaglandins, leukotriens, thromboxans) during inflammatory
      process.

PMID- 22629609
TI  - Removal of microcystin-LR from spiked water using either activated carbon or
      anthracite as filter material.
AB  - The occurrence of cyanobacterial toxins (blue-green algae) in drinking water
      sources is a big concern for human health. Removal of microcystin-LR (MC-LR) from
      drinking water was evaluated at the laboratory pilot scale using either granular
      activated carbon (GAC) or powdered activated carbon (PAC) and compared with the
      treatment using anthracite as filter material. Virgin GAC was more effective at
      removing MC-LR (initial concentration ranging from 9 to 47 microg L(-1)) to reach
      the World Health Organization recommended level (1.0 microg L(-1)). When the GAC
      filter was colonized by bacteria, the filter became less effective at removing MC
      LR owing to competitive reactions occurring between protein adsorption (released
      by bacteria) and MC-LR adsorption. Using PAC, the concentration of MC-LR
      decreased from 22 to 3 microg L(-1) (removal of 86% of MC-LR) by the addition of
      100 mg PAC L(-1).

PMID- 22629610
TI  - Effect of surface modification of microfiltration membrane on capture of toxic
      heavy metal ions.
AB  - A novel complexing membrane containing 8-hydroxyquinoline groups was used for the
      removal of heavy metal ions (Cd2+ and Ni2+) from aqueous solution. The
      functionalized membranes were characterized by FTIR-ATR, SEM and EDAX for the
      presence of functional groups, the physical structure of the membranes and the
      analysis of the particles deposited on the membrane, respectively. The influence
      of 8-hydroxyquinoline concentration, feed concentration, pH and temperature of
      the solution on capture capability was studied. The modified membrane showed a
      higher affinity to Cd2+ cations than to Ni2+. The metal ion rejection was
      increased with an increase in concentration of 8-hydroxyquinoline from 0.5 to 2.0
      wt%. However at a ligand concentration higher than 2.0 wt%, no significant change
      was observed in the metal rejection. The experimental results revealed that the
      metal rejection was decreased with an increase in metal ion concentration in the
      feed. Moreover the rejection depended on feed pH and is higher for elevated pH.
      By changing the temperature in the range of 23-28 degrees C, no considerable
      effect on metal rejection was observed. However, a higher temperature resulted in
      a decline in metal rejection. For filtration of a mixture of the two metal ions,
      the retention was similar to that of the single cations, i.e. Cd > Ni but with
      smaller absolute rejections.

PMID- 22629611
TI  - Nitrous oxide production from sequencing batch reactor sludge under nitrifying
      conditions: effect of nitrite concentrations.
AB  - Nitrous oxide (N2O), a greenhouse gas which contributes to the destruction of the
      stratospheric ozone layer, can be emitted from nitrifying processes during
      wastewater treatment. The pathway of N2O production was studied using a lab-scale
      nitrifying reactor. Allylthiourea was used to inhibit NH4+ oxidation and provide
      information on processes that happen under nitrifying condition. Our study
      confirmed that besides heterotrophic bacteria, ammonium-oxidizing bacteria could
      perform denitrification processes, during which NO2- was the electron acceptor
      and NH4+ was the electron donor, with N2 and N2O as final products. The relative
      contribution of the heterotrophic denitrification process to total N2O emissions
      varied from 46.1% to 60.4% depending on NO2(-)-N addition. Correspondingly, 21.8%
      to 51.5% of total N2O emissions can be attributed to nitrifier denitrification.
      Little N2O is emitted during the NO2- oxidation process.

PMID- 22629612
TI  - Kinetics modelling of Cu(II) biosorption on to coconut shell and Moringa oleifera
      seeds from tropical regions.
AB  - Adsorption kinetic studies are of great significance in evaluating the
      performance of a given adsorbent and gaining insight into the underlying
      mechanism. This work investigated the sorption kinetics of Cu(II) on to coconut
      shell and Moringa oleifera seeds using batch techniques. To understand the
      mechanisms of the biosorption process and the potential rate-controlling steps,
      kinetic models were used to fit the experimental data. The results indicate that
      kinetic data were best described by the pseudo-second-order model with
      correlation coefficients (R2) of 0.9974 and 0.9958 for the coconut shell and
      Moringa oleifera seeds, respectively. The initial sorption rates obtained for
      coconut shell and Moringa oleifera seeds were 9.6395 x 10(-3) and 8.3292 x 10(-2)
      mg g(-1) min(-1), respectively. The values of the mass transfer coefficients
      obtained for coconut shell (1.2106 x 10(-3) cm s(-1)) and Moringa oleifera seeds
      (8.965 x 10(-4) cm s(-1)) indicate that the transport of Cu(II) from the bulk
      liquid to the solid phase was quite fast for both materials investigated. The
      results indicate that intraparticle diffusion controls the rate of sorption in
      this study; however, film diffusion cannot be neglected, especially at the
      initial stage of sorption.

PMID- 22629613
TI  - The hydroxyl radical scavenging effect of textile preparation auxiliaries on the
      photochemical treatment of nonylphenol ethoxylate.
AB  - The present paper deals with the effects of frequently used textile preparation
      chemicals and common ions on the H2O2/UV-C treatment of a commercially important
      and slowly biodegradable nonionic surfactant, namely a nonylphenol bearing 10
      ethoxylated chains. For this purpose, the effect of soda ash carbonate (0-5.0 g
      L(-1)), two phosphonic acid-based organic sequestering agents (0-2.5 g L(-1)) and
      chloride (0-3.0 g L(-1)) at two different pH values (3.5 and 10.5) as hydroxyl
      radical scavengers was experimentally investigated. Among the studied textile
      preparation chemicals and hydroxyl radical scavengers, the decreasing order of
      hydroxyl radical scavenging capacity was established as diethylene triamine
      pentamethylene phosphonic acid > 1-hydroxy ethylidene-1,1-diphosphonic acid >
      soda ash carbonate at pH 10.5 > chloride at pH 3.5 > chloride at pH 10.5.

PMID- 22629614
TI  - Treatment of fruit-juice industry wastewater in a two-stage anaerobic hybrid (AH)
      reactor system followed by a sequencing batch reactor (SBR).
AB  - This study has been carried out to assess the performance of a combined system
      consisting of an anaerobic hybrid (AH) reactor followed by a sequencing batch
      reactor (SBR) for treatment of fruit-juice industry wastewater at a temperature
      of 26 degrees C. Three experimental runs were conducted in this investigation. In
      the first experiment, a single-stage AH reactor was operated at a hydraulic
      retention time (HRT) of 10.2 h and organic loading rate (OLR) of 11.8 kg COD m(
      3) d(-1). The reactor achieved a removal efficiency of 42% for chemical oxygen
      demand (COD), 50.8% for biochemical oxygen demand (BOD5), 50.3% for volatile
      fatty acids (VFA) and 56.4% for total suspended solids (TSS). In the second
      experiment, two AH reactors connected in series achieved a higher removal
      efficiency for COD (67.4%), BOD5 (77%), and TSS (71.5%) at a total HRT of 20 h
      and an OLR of 5.9 kg COD m(-3) d(-1). For removal of the remaining portions of
      COD, BOD5 and TSS from the effluent of the two-stage AH system, a sequencing
      batch reactor (SBR) was investigated as a post-treatment unit. The reactor
      achieved a substantial reduction in total COD, resulting in an average effluent
      concentration of 50 mg L(-1) at an HRT of 11 h and OLR of 5.3 kg COD m(-3) d(-1).
      Almost complete removal of total BOD5 and oil and grease was achieved, i.e. 10 mg
      L(-1) and 1.2 mg L(-1), respectively, remained in the final effluent of the SBR.

PMID- 22629615
TI  - Evaluation of DNA extraction methods for the analysis of microbial community in
      biological activated carbon.
AB  - It is difficult to isolate DNA from biological activated carbon (BAC) samples
      used in water treatment plants, owing to the scarcity of microorganisms in BAC
      samples. The aim of this study was to identify DNA extraction methods suitable
      for a long-term, comprehensive ecological analysis of BAC microbial communities.
      To identify a procedure that can produce high molecular weight DNA, maximizes
      detectable diversity and is relatively free from contaminants, the microwave
      extraction method, the cetyltrimethylammonium bromide (CTAB) extraction method, a
      commercial DNA extraction kit, and the ultrasonic extraction method were used for
      the extraction of DNA from BAC samples. Spectrophotometry, agarose gel
      electrophoresis and polymerase chain reaction (PCR)-restriction fragment length
      polymorphisms (RFLP) analysis were conducted to compare the yield and quality of
      DNA obtained using these methods. The results showed that the CTAB method produce
      the highest yield and genetic diversity of DNA from BAC samples, but DNA purity
      was slightly less than that obtained with the DNA extraction-kit method. This
      study provides a theoretical basis for establishing and selecting DNA extraction
      methods for BAC samples.

PMID- 22629616
TI  - Comparison of As, Ni, Zn, Cd, and Pb removals using treatment agents.
AB  - The removal of heavy metals, such as As, Ni, Zn, Cd and Pb, onto limestone,
      starfish, black shale and concrete from wastewater was studied. These materials,
      with a high capacity for heavy metals, can be obtained and employed as
      alternative low-cost substitutes. Various parameters, such as the neutralization
      capacity, changes in pH, redox potential and electric conductivity as a function
      of time, were quantified. Of the studied treatment agents, concrete showed high
      neutralization efficiency for acid mine drainage and maintained a pH value above
      11. The adsorption of heavy metals was influenced by the compositions of the
      treatment agents. The experimental results of leaching revealed no significant
      follow-up release from any of the treatment agents. The results suggest that
      concrete could be used successfully for the treatment of mixed metal-contaminated
      wastes.

PMID- 22629617
TI  - A novel fluidized bed respirometric technique for determination of in situ
      biofilm kinetics.
AB  - A respirometric approach has been developed to determine heterotrophic biofilm
      kinetics using fluidized bioparticles--particles with attached biomass. Lava rock
      particles of 600 microm were used as a biomass carrier medium. The modified
      respirometer successfully estimates in situ biofilm kinetics of the bioparticles
      collected from a pilot-scale liquid-solid circulating fluidized bed (LSCFB)
      bioreactor. The observed maximum specific growth rates (micro(max)) of 3.69 +/-
      0.44 d(-1) and biomass yields (Y(H)) of 0.36 +/- 0.03 g COD/g COD in the
      fluidized bed respirometers were significantly different from the micro(max) of
      5.57-5.72 d(-1) and Y(H) of 0.54-0.59 g COD/g COD observed in the conventional
      respirometric tests for bioparticles and detached biomass. The higher Monod half
      saturation coefficient (K(S)) of 186-219mg COD/L observed in the fluidized bed
      respirometers relative to the 49-58 mg COD/L in the conventional respirometers
      reveals the presence of mass transfer resistance in the LSCFB despite
      fluidization. Significantly reduced yields in the fluidized bed respirometers and
      the estimated maintenance coefficient of 1.16 d(-1) for the particulate biofilm
      in the LSCFB clearly emphasize that a substantial amount of substrate was
      utilized for cell maintenance at the low food to microorganism (S/X) ratio of 0.5
      g COD/g VSS.

PMID- 22629618
TI  - CeO2 mediated photocatalytic degradation studies of C.I. acid orange 7.
AB  - CeO2 nanoparticles were prepared by a simple precipitation method, followed by
      calcination treatment. By selecting photocatalytic degradation of acid orange 7
      (AO7) as a probe reaction, the influences of calcination temperature of catalyst,
      the concentration of AO7, initial pH value of AO7 solution and catalyst dosage on
      the photocatalytic activity of CeO2 were studied. It was found that CeO2 calcined
      at 550 degrees C shows the highest photocatalytic activity under visible light
      irradiation. It was revealed that under visible light irradiation the degradation
      of AO7 over CeO2 nanoparticles follows a dye self-sensitization mechanism. The
      degradation rate of AO7 increases with decrease in the initial pH value of the
      reaction solution, and degradation efficiency decreases with increase in the
      initial dye concentration. The optimal dosage of CeO2 in solution for AO7
      degradation is 1 g/L.

PMID- 22629619
TI  - Synthesis, characterization and applications of a new cation exchanger tamarind
      sulphonic acid (TSA) resin.
AB  - A new composite cation exchanger, tamarind sulphonic acid (TSA) resin has been
      synthesized. The chemically modified TSA ion exchange resin has been used for the
      removal and preconcentration of Zn2+, Cd2+, Fe2+, Co2+ and Cu2+ ions in aqueous
      solution and effluent from the Laxmi steel plant in Jodhpur, India. This type of
      composite represents a new class of hybrid ion exchangers with good ion exchange
      capacity, stability, reproducibility and selectivity for toxic metal ions found
      in effluent from the steel industry. The characterization of the resin was
      carried out by determining the ion-exchange capacity, elemental analysis, pH
      titration, Fourier transform infrared spectra and thermal analysis. The
      distribution coefficients (K(d)) of toxic metal ions were determined in a
      reference aqueous solution and the steel plant effluent at different pH values;
      the absorbency of different metal ions on the TSA resin was studied for up to 10
      cycles. The adsorption of different metal ions on TSA resin follows the order:
      Co2+ > Cu2+ > Zn2+ > Fe2+ > Cd2+. The ion exchange capacity of TSA resin is
      2.87%.

PMID- 22629620
TI  - Characteristics and oil sorption effectiveness of kapok fibre, sugarcane bagasse
      and rice husks: oil removal suitability matrix.
AB  - The characteristics and water/oil sorption effectiveness ofkapok fibre, sugarcane
      bagasse and rice husks have been compared. The three biomass types were subjected
      to field emission scanning electron microscopy-energy dispersive X-ray
      spectroscopy and surface tension analyses for liquid-air and oil-water systems
      were conducted. Both kapok fibre and sugarcane bagasse exhibit excellent oil
      sorption capabilities for diesel, crude, new engine and used engine oils as their
      oil sorption capacities all exceed 10 g/g. The synthetic sorbent exhibits oil
      sorption capacities comparable with sugarcane bagasse, while rice husks exhibit
      the lowest oil sorption capacities among all the sorbents. Kapok fibre shows
      overwhelmingly high oil-to-water sorption (O/W) ratios ranging from 19.35 to
      201.53 while sugarcane bagasse, rice husks and synthetic sorbent have
      significantly lower O/W ratios (0.76-2.69). This suggests that kapok fibre is a
      highly effective oil sorbent even in well-mixed oil-water media. An oil sorbent
      suitability matrix is proposed to aid stakeholders in evaluating customized oil
      removal usage of the natural sorbents.

PMID- 22629621
TI  - Control of disinfection by-product formation using ozone-based advanced oxidation
      processes.
AB  - The effects of ozone dosage, water temperature and catalyst addition in an
      ozonation-fluidized bed reactor (O3/FBR) on treated water quality and on the
      control of chlorinated and ozonated disinfection by-products (DBPs) were
      investigated. A biofiltration column was used to evaluate its removal efficiency
      on biodegradable organic matter and to reduce DBP formation. The Dong-Gang River,
      polluted by agricultural and domestic wastewater in Pingtung, Taiwan, was used as
      the water source. The treated water quality in terms of dissolved organic carbon
      (DOC), biodegradable DOC, ultraviolet absorbance at 254 nm (UV254) and specific
      UV absorbance (SUVA) improved with increasing ozone and catalyst dosages.
      Catalytic ozonation was more effective than ozonation alone at reducing the
      formation of DBPs at a given dosage. Experimental results show that water
      temperature had little effect on the treated water quality with the O3/FBR system
      used in this study (p > 0.05). The combination of O3/FBR and the biofiltration
      process effectively decreased the amount ofDBP precursors. The concentration of
      total trihalomethanes (TTHMs) was less than the maximum contaminant level (MCL)
      requirement, which is 80 microg/L, for all treated waters and the concentration
      of five haloacetic acids (HAA5) fell below 60 microg/L with an ozone dosage
      higher than 2.5 mg/L.

PMID- 22629622
TI  - Effect of oxygen injection in a reclaimed wastewater pipeline on the
      microbiological quality of water.
AB  - In this work the influence of oxygen injection on the inactivation of
      microbiological indicators during reclaimed wastewater transportation was
      studied. Experiments were carried out in a completely filled gravity pipe (62 km
      long), at two different periods of the year and with three different oxygen doses
      (7, 15 and 30 mg L(-1)). Microbiological parameters studied were faecal
      coliforms, Escherichia coli, enterococci and somatic coliphages. As a consequence
      of the oxygen injection, a significant inactivation of the microbiological
      parameters was observed during the aerobic stretch of the pipe. Later, once the
      oxygen had been consumed, inactivation stopped and even a slight regrowth of the
      microbial population took place. Inactivations were within the range of 0.6-1.0
      log10 units, in most cases. No significant differences between inactivations for
      the different microbiological parameters were found, except for the somatic
      coliphages. A relationship between the inactivation degree and oxygen dose and
      organic matter content was observed. The biofilm played an important role in the
      inactivation process. The injection of oxygen contributes to improving the
      microbiological quality of reclaimed wastewater during its transport by
      pipelines, helping to diminish the subsequent on-site disinfection requirements.

PMID- 22629623
TI  - Modelling temperature variations and moisture requirements in waste air
      biofilters under steady-state conditions.
AB  - In this paper a mechanistic model is presented for the estimation of temperature
      variations, moisture requirements, and elimination capacity of a waste air
      biofilter. The model considers diffusion and biodegradation of the pollutant in
      the biofilm, heat generation due to the bioreaction, and water evaporation from
      the solid media due to heat generation. Mass and energy balances were employed to
      derive the equations of the model. The equations were solved numerically using
      the finite volume method. The model was used to describe a set of experimental
      data for methane removal in a bench-scale biofilter. The model showed that an
      increase in elimination capacity caused a temperature rise in the biofilter. The
      model also showed that the air temperature and humidity increased along the
      height of the biofilter in the direction of airflow. The rate of increase in air
      humidity was higher in the first segment of the biofilter, indicating higher
      moisture requirement in this segment. A stoichiometric approach was adopted to
      estimate carbon dioxide production in the biofilter. The model predictions were
      in good agreement with the experimental data.

PMID- 22629624
TI  - Oxidative decolorization of methylene blue by leached sea-nodule residues
      generated by the reduction-roasting ammoniacal leaching process.
AB  - The leached residue, generated after selective extraction of Cu, Ni and Co by
      reductive-roasting ammoniacal leaching of sea nodules, was characterized by
      various physicochemical methods. The finely divided residue, containing mainly
      manganese carbonate/silicates and manganese (III, IV) (hydr)oxides along with
      iron oxides, showed a lower surface area (66.3 m2 g(-1)) than that of the parent
      sea nodule (130 m2 g(-1)). The catalytic efficiency of water-washed sea nodule
      residue (WSNR) was evaluated taking oxidative decolorization of methylene blue
      (MB) as the test reaction. The extent of decolorization was decreased with
      increase in pH but increased in the presence of H2O2 or NaCl. Decolorization of
      MB occurred in two consecutive steps; the rate constant of the first step was -10
      times higher than that of the second step. The formation of a surface precursor
      complex between WSNR and MB at a rate-limiting step, followed by electron
      transfer from MB to the active metal centre of WSNR and release of product(s),
      was proposed as the decolorization process.

PMID- 22629625
TI  - Determination of the trophic situation in Gheshlagh reservoir (North-Western
      Iran).
AB  - 'Trophic state' is often used to classify aquatic ecosystems according to biotic
      productivity. Carlson trophic state indices were used to assess the trophic
      situation in Gheshlagh reservoir (North-Western Iran), on which a dam was
      constructed three decades ago. Using data from a one-year surface sampling, a
      comparison of the trophic state index (TSI), between four sampling points in the
      reservoir and one sampling point under the dam, was performed. The results of the
      TSI calculated based on chlorophyll a (chl. a) concentration and Secchi depth
      showed that the aquatic environment in the reservoir is eutrophied (50 < TSI <
      80), while it is mesotrophic (40 < TSI < 50) under the dam. Moreover, the
      measured concentrations of chl. a and phosphate were consistent with the
      available data ranges on eutrophication. In addition, it was shown that algal
      biomass bloom occurred at the end of spring, all over the sampling points.

PMID- 22629626
TI  - Effect of VOCs and methane in the biological oxidation of the ferrous ion by an
      acidophilic consortium.
AB  - During the elimination of H2S from biogas in an aqueous ferric sulphate solution,
      volatile organic compounds (VOCs) and methane are absorbed and may have an effect
      on the subsequent biological regeneration of ferric ion. This study was conducted
      to investigate the effect of maximum concentrations of methane and some VOCs
      found in biogas on the ferrous oxidation of an acidophilic microbial consortium
      (FO consortium). The presence and impact of heterotrophic microorganisms on the
      activity of the acidophilic consortium was also evaluated. No effect on the
      ferrous oxidation rate was found with gas concentrations of 1500 mg toluene m(
      3), 1400 mg 2-butanol m(-3) or 1250 mg 1,2-dichloroethane m(-3), nor with methane
      at gas concentrations ranging from 15-25% (v/v). A tenfold increase in VOCs
      concentrations totally inhibited the microbial activity of the FO consortium and
      the heterotrophs. The presence of a heterotrophic fungus may promote the
      autotrophic growth of the FO consortium.

PMID- 22629627
TI  - Use of solar radiation for continuous water disinfection in isolated areas.
AB  - This study involved investigation of solar water disinfection in continuously
      working treatment plants with the aim of producing safe drinking water in
      isolated areas. Results were obtained from experimental work carried out on a
      pilot plant operating in different configurations. The use of a simple device to
      increase solar radiation intensity (solar concentrator) was tested, with results
      showing that it facilitated better performance. A comparison between transparent
      and black-painted glass reactors was also made, showing no difference between the
      two casings. Further, the effect of an increase in water temperature was analysed
      in detail. Temperature was found to play an important role in the disinfection
      process, even in cases of limited solar radiation intensities, although a
      synergistic effect of water heating and solar radiation for effective microbial
      inactivation was confirmed. Reactor design is also discussed, highlighting the
      importance of having a plug flow to avoid zones that do not contribute to the
      overall effectiveness of the process.

PMID- 22629628
TI  - Removal of remazol yellow from aqueous solution using Fe-Cu and Fe-Ni nanoscale
      oxides and their carbonaceous composites.
AB  - Fe-Cu and Fe-Ni nanoscale oxides and their carbonaceous composites (C/Fe-Cu and
      C/Fe-Ni, 75/25 wt.%; C/Fe-Cu and C/Fe-Ni 95/5 wt.%), made from pyrolysis of
      sewage sludge, have been evaluated to remove remazol yellow textile dye from
      aqueous solution. The kinetic and sorption isotherms experimental results were
      best fitted to the pseudo-second-order kinetic and Langmuir-Freundlich isotherm
      models, which indicates that the sorption mechanism may be chemisorption onto
      heterogeneous surfaces. Fe-Ni and Fe-Cu nanoscale oxides adsorption capacities
      were 157.8 mg/g and 117.6 mg/g, resulting in nearly 83% and 70% of dye removal,
      respectively, using 100 mg/L of initial dyestuff concentration and 10 mg of each
      material. The adsorption capacities of Fe-Cu, Fe-Ni oxides and C/FCu 75/25%, C/Fe
      Ni 75/25% composites provide better results at pH between 3 and 5. In addition,
      three sorption-desorption cycles using 30% H2O2 solution and distilled water were
      performed: sorption efficiencies for all materials decreased after each cycle;
      nevertheless, Fe-Cu and Fe-Ni nanoscale oxides were the best materials for the
      removal of remazol yellow dye.

PMID- 22629629
TI  - Identifying the cause of soil cadmium contamination with Monte Carlo mass balance
      modelling: a case study from Potosi, Bolivia.
AB  - The Chayanta river in Potosi, Bolivia is polluted by present and past mining
      activities in the districts of Siglo XX and Llallagua. The river water, which is
      enriched with cadmium (Cd), is used for irrigation in the Quila Quila and Asiruri
      valleys where the median soil Cd concentration is 20 mg kg(-1), well above the
      background value of < 0.5 mg kg(-1). The objective of this study was to predict
      current soil contamination using a retrospective mass balance. Monitoring data
      were collected on Cd concentrations in irrigation water, irrigation application
      rates, crop yield and composition, and soil properties including pore water
      composition. The mass balance was made assuming constant model parameters since
      the start of upstream mining operations about 85 years ago (1920). The parameter
      uncertainty was taken into account with a Monte Carlo analysis. The current
      annual Cd input by irrigation is 800 g ha(-1). The annual output of Cd through
      removal of the crop harvest and leaching is less than 10 g ha(-1). The predicted
      soil Cd concentrations after 85 years of contamination (geometric mean: 21.9 mg x
      kg(-1), 10th and 90th percentile 7.2-65.1 mg kg(-1) respectively) matched the
      distribution of observed values (geometric mean: 18.6 mg kg(-1); 10th and 90th
      percentile 4.7-65.9 mg kg(-1) respectively; n = 56). This study confirmed that
      irrigation water is the prime source of soil Cd enrichment in that area. The
      Monte Carlo analysis is a convenient way of including parameter uncertainty in
      mass balance modelling and of estimating spatial variability of the
      contamination.

PMID- 22629630
TI  - Disposal of post-consumer polyethylene terephthalate (PET) bottles: comparison of
      five disposal alternatives in the small island state of Mauritius using a life
      cycle assessment tool.
AB  - Used polyethylene terephthalate bottles (PET) dumped indiscriminately onto bare
      lands and water bodies constitute an eyesore. This problem is viewed as a serious
      impediment to the flourishing tourism industry in Mauritius. Currently, over 100
      million PET bottles are generated annually and the only fully operational
      disposal route is through the sole sanitary landfill. There is no formal
      segregation of waste and therefore used PET bottles are disposed of commingled
      with domestic waste. Despite a satisfactory waste collection system, a
      considerable amount of used PET bottles unfortunately end up in water bodies and
      on bare lands. An appreciable amount of PET bottles is now being collected
      separately for flake production prior to export to South Africa. This paper
      investigated the environmental impact of five waste management scenarios (100%
      landfill; 100% incineration with energy recovery; 50% incineration and 50%
      landfill; 34% flake production and 66% landfill; 100% flake production) for used
      PET bottles in Mauritius. Comparison of the five scenarios was based on the life
      cycle assessment (LCA) methodology described in ISO 14040 and ISO 14044. SimaPro
      7.1 software was used to analyse the data. Comparison of the five scenarios
      showed that the highest environmental impacts occurred when 100% of used PET
      bottles were sent to the landfill. The comparison also indicated that there were
      least impacts on the environment when all used PET bottles were incinerated with
      energy recovery.

PMID- 22629631
TI  - Effect of temperature on survival of micro-organisms and performance of anaerobic
      two-stage reactors treating cattle slurry.
AB  - A short-term thermophilic treatment was conducted in order to study the survival
      of micro-organisms in slurry derived from a cattle farm, at temperatures of 58,
      63 and 68 degrees C for 6 h. The second trial was a biogas production experiment
      with an anaerobic mesophilic first stage and a thermophilic second stage. The
      mesophilic treatment was at 38 degrees C and the second stage was conducted at
      55, 58 or 65 degrees C. The results of first trial showed that survival of micro
      organisms was decreased remarkably at higher temperatures in spite of the fact
      that during the experiment part of slurry was replaced with fresh slurry.
      Meanwhile, the second trial showed that optimum production ofbiogas was at 55
      degrees C while the best result for hygienic control was achieved at 65 degrees
      C.

PMID- 22629632
TI  - Strategies to enhance the biological nitrogen removal of high-strength ammonium
      and low C/N landfill leachate with the SBR process.
AB  - The treatment of high ammonium-nitrogen concentration landfill leachate has
      become an increasing problem because of the requirements to reduce nutrient
      emissions. A laboratory-scale sequential batch reactor (SBR) was operated and
      tested in order to optimize the operational strategies of a cost-saving method to
      enhance the removal of ammonium-nitrogen from a real landfill leachate. Two
      sequence schemes were tested, one with long non-aerated/aerated sequences and
      another with short sequences. The air supply levels with low to intermediate
      dissolved oxygen (DO) and external carbon addition were altered. With both
      schemes a high ammonium reduction (> 99%) and a reasonable total nitrogen (TN)
      reduction (around 60%) could be achieved with strong carbon limitation (BOD7/N =
      1.1). Chemical oxygen demand (COD) removal was lower with longer sequences.
      Denitrification via nitrite seemed to be an important part of TN removal,
      controlled with the low DO. With increasing nitrite accumulation COD/N removed
      decreased in both schemes indicating clearly a more efficient use of COD. The
      scheme with short sequences indicated advantages to save the air supply
      preventing nitrite oxidation under low air supply conditions and better TN and
      COD removal efficiencies. The results show that an applicable operational
      strategy can be found resulting in a reasonable pre-treatment option in
      landfills, requiring less carbon and aeration energy.

PMID- 22629633
TI  - Utilization of brewery wastewater for culturing yeast cells for use in river
      water remediation.
AB  - Successful in situ bio-augmentation of contaminated river water involves reducing
      the cost of the bio-agent. In this study, brewery wastewater was used to culture
      yeast cells for degrading the COD(Cr) from a contaminated river. The results
      showed that 15 g/L of yeast cells could be achieved after being cultured in the
      autoclaved brewery wastewater with 5 mL/L of saccharified starch and 9 g/L of
      corn steep liquor. The COD(Cr) removal efficiency was increased from 22% to 33%
      when the cells were cultured using the mentioned method. Based on the market
      price of materials used in this method, the cost of the medium for remediating 1
      m3 of river water was 0.0076 US dollars. If the additional cost of field
      implementation is included, the total cost is less than 0.016 US dollars for
      treating 1 m3 of river water. The final cost was dependent on the size of
      remediation: the larger the scale, the lower the cost. By this method, the
      nutrient in the brewery wastewater was reused, the cost of brewery wastewater
      treatment was saved and the cost of the remediation using bio-augmentation was
      reduced. Hence, it is suggested that using brewery wastewater to culture a bio
      agent for bio-augmentation is a cost-effective method.

PMID- 22629634
TI  - Adsorptive removal of cadmium by natural red earth: equilibrium and kinetic
      studies.
AB  - Natural red earth (NRE), an iron-coated sand found in the north western part of
      Sri Lanka, was used to examine the retention behaviour of cadmium, a heavy metal
      postulated as a factor of chronic kidney disease in Sri Lanka. Adsorption studies
      were conducted as a function of pH, ionic strength, initial Cd loading and time.
      The Cd adsorption increased from 6% to 99% with the pH increase from 4 to 8.5.
      The maximum adsorption was reached at pH > 7.5. Cadmium adsorption was not
      changed over 100-fold variations of NaNO3, providing evidence for the dominance
      of an inner-sphere bonding mechanism for both 10-fold variation of initial Cd
      concentrations. Surface complexation modelling suggests a monodentate bonding
      mechanism. Isotherm data were fairly fitted to a two-site Langmuir isotherm model
      and sorption maximums of 9.11 x 10(-6) and 3.89 x 10(-7) mol g(-1) were obtained
      for two surface sites. The kinetic study reveals that Cd uptake by NRE is so fast
      that the equilibrium was reached within 15 min and - 1 h for 4.44 and 44.4 microM
      initial Cd concentrations, respectively, and the chemisorption was the dominant
      mechanism over intra-particle diffusion. The study indicates the potential of NRE
      as a material for decontaminating environmental water polluted with Cd.

PMID- 22629635
TI  - Modelling of integrated anoxic-anaerobic-aerobic treatment for salmon fishery
      wastewater in an upflow fixed-bed biofilm reactor.
AB  - Literature has paid scarce attention to the modelling of the integrated anoxic
      anaerobic-aerobic process in upflow fixed-bed biofilm reactors used to treat
      wastewater. The present study developed a model for industrial salmon fishery
      wastewater treatment in an integrated anoxic-anaerobic-aerobic upflow fixed-bed
      biofilm reactor. The model successfully predicted the removal efficiency of both
      Chemical Oxygen Demand (COD) and nitrogen for two recycle ratios at steady state.
      The simulation study shows that the COD removal efficiency is not affected by any
      parameter under the studied conditions, while the nitrogen removal efficiency is
      affected by the hydraulic retention time (HRT) and the inlet COD concentration,
      where Total Ammonia Nitrogen (TAN) is the most sensitive variable of the anoxic
      anaerobic-aerobic system. The conditions that best obtained removal efficiencies
      above 70% are: recycle rate between 1 and 2; HRT between 1.4 and 2.2 days and
      inlet COD concentrations lower than 2500 mg COD L(-1). Analysis of the model's
      sensitivity indicated that the parameters that exert most influence on the model
      for the system were micro(max,M), k(h), micro(max,H), eta(NO3-), micro(NOB),
      K(DO)NOB and D(DO).

PMID- 22629636
TI  - Remediation potential of mulch for removing lead.
AB  - Hardwood bark mulch has good physicochemical properties for the adsorption of
      lead (Pb(II)). Batch tests were conducted to obtain the sorption coefficient of
      Pb(II) in mulch. The results of the Freundlich model were not in as good
      agreement as for the case of the Langmuir model. In addition, a laboratory-scale
      mulch permeable reactive barrier (PRB) system was designed for the treatment of
      Pb(II)-contaminated groundwater. The mulch PRB system, using a mulch layer, can
      potentially be used in the subsurface for cost-effective and in situ
      transformation of the Pb(II) into environmentally acceptable forms. From the
      Pb(II) breakthrough curve, the mulch becomes saturated more quickly at higher
      flow rates.

PMID- 22629637
TI  - Effect of process conditions on the steam reforming of ethanol with a nano
      Ni/SiO2 catalyst.
AB  - In this paper, a nano-Ni/SiO2 catalyst was prepared by a sol-gel method and
      tested for hydrogen production from ethanol steam reforming using a two-stage
      fixed-bed reaction system. The reaction conditions, such as reaction temperature,
      water/ethanol ratio and sample feeding rate, were investigated with the prepared
      nano-Ni/SiO2 catalyst. Brunauer-Emmett-Teller surface area and porosity,
      temperature-programmed oxidation, X-ray diffraction and focused ion beam
      (FIB)/scanning electron microscopy were used in this work to analysis the fresh
      and/or reacted catalysts. An extended catalyst stability test for ethanol steam
      reforming with the Ni/SiO2 catalyst was carried out at a reaction temperature of
      600 degrees C, when the water/ethanol ratio was kept at 3.5 and sample feeding
      rate was 4.74 g h(-1). The results showed that a stabilized gas and hydrogen
      production was obtained with a potential H2 production of about 40 wt.%.
      Increasing the reaction temperature during ethanol steam reforming with the
      Ni/SiO2 catalyst resulted in an increase of gas and hydrogen production. The gas
      yield was slightly reduced when the water/ethanol ratio was increased from 2.0 to
      3.5. However, the potential H2 production was increased. The investigation of the
      sample feeding rate showed that the gas production per hour was increased due to
      the higher sample feeding rate, but the potential H2 production was reduced.

PMID- 22629638
TI  - Recycling of woven carbon-fibre-reinforced polymer composites using supercritical
      water.
AB  - Over the past few years, there has been great deal of interest in recycling
      carbon-fibre-reinforced polymer composites. One method that has shown promising
      results involves the use of supercritical fluids to achieve separation between
      matrix and fibres by effectively degrading the resin into lower molecular weight
      compounds. In addition, the solvents used are environmentally benign and can also
      be recovered and reused. In this study, supercritical water with 0.05 M KOH as
      the catalyst was used for the recycling of an aerospace-grade high-performance
      epoxy carbon fibre composite (Hexcel 8552/IM7). The morphology of the reclaimed
      fibres was observed by scanning electron microscopy, and the tensile properties
      of the fibres were measured by single filament testing. The effects of processing
      time on the resin elimination efficiency and fibre property retention were
      investigated. With the process developed in this research, as much as 99.2 wt%
      resin elimination was achieved, resulting in the recovery of clean, undamaged
      fibres. The reclaimed fibres retained the original tensile strength. The
      feasibility of recycling multiple layer composites was also explored.

PMID- 22629639
TI  - Role of plasmid in diesel oil degradation by yeast species isolated from
      petroleum hydrocarbon-contaminated soil.
AB  - Five yeast species, namely Candida tropicalis, Cryptococcus laurentii,
      Trichosporon asahii, Rhodotorula mucilaginosa and Candida rugosa isolated from
      hydrocarbon-contaminated soil were found to be potent degraders of diesel oil.
      These microorganisms showed the presence of enzymes cytochrome P450, NADPH
      cytochrome c reductase, aminopyrine N demethylase, alcohol dehydrogenase,
      aldehyde dehydrogenase, naphthalene dioxygenase, catalase and glutathione S
      transferase when the cells were incubated for 48 h in Bushnell Haas medium
      supplemented with 2% diesel oil as the sole source of carbon. The cytochrome P450
      monooxygenase enzyme system was found to play an important role in diesel oil
      degradation. A plasmid approximately 12kb in size was found to be harboured by
      all the yeast species. The role of the plasmid on diesel oil degradation was
      assessed by biomass inhibition studies, which confirmed that the metabolic
      machinery of yeast species for diesel oil degradation was plasmid coded. This is
      the first report establishing the involvement of a plasmid in diesel oil
      degradation by yeast species.

PMID- 22629640
TI  - Individual treatment of hotel and restaurant waste water in rural areas.
AB  - About 25 hotels, restaurants and pubs in the rural community Heuvelland are
      situated in the area designated for individual water treatment. In order to meet
      the legislation by the end of 2015, each business needs to install an individual
      waste water treatment system (IWTS). To study this situation, three catering
      businesses were selected for further research. The aim of the study was to
      quantify the effluent quality and to assess IWTS performance for these catering
      businesses. First of all, the influence of discharging untreated waste water on
      the receiving surface water was examined. The results showed a decrease in water
      quality after the discharge point at every business. With the collected data,
      simulations with the software WEST were performed. With this software two types
      of IWTSs with different (buffer) volumes were modelled and tested for each
      catering business. The first type is a completely mixed activated sludge reactor
      and the second type is a submerged aerobic fixed-bed reactor. The results of
      these simulations demonstrate that purification with an IWTS is possible if the
      capacity is large enough and if an adequate buffer volume is installed and if
      regular maintenance is performed.

PMID- 22629641
TI  - Decomposition of dichlorobenzene in a dielectric barrier discharge.
AB  - This paper presents a decomposition study of 1,2-dichlorobenzene (DCB) using a
      dielectric barrier discharge (DBD). The discussion is focused on the effects of
      variations of carrier gases, DCB concentrations and input voltages on the
      decomposition performance. The DCB conversion was conducted inside a cylindrical
      reactor consists of silver film as the outside electrode and a spring coil as the
      inside electrode. Two carrier gases, i.e. air and nitrogen, were introduced to
      the reactor at a total flow rate of 500 mL/min with DCB concentrations of 100,
      300 and 500 ppm. Gaseous products, before and after plasma treatment, were
      analysed by a gas chromatography and FT-IR spectroscopy, and the consumed power
      was calculated from Lissajous' figure analysis. In order to improve the
      decomposition performance, various TiO2-supported catalysts were employed.

PMID- 22629642
TI  - Performance of a sand filter in removal of micro-algae from seawater in
      aquaculture production systems.
AB  - In this study, a sand filter was used to remove micro-algae from seawater feeding
      aquaculture ponds. A lab-scale sand filter was used to filter 30,000 cells/mL of
      Heterocapsa triquetra suspension, a non-toxic micro-alga that has morphological
      and dimensional (15-20 microm) similarities with Alexandrium sp., one of the
      smallest toxic micro-algae in seawater. Removal efficiency and capture mechanisms
      for a fixed superficial velocity (3.5 m/h) were evaluated in relation to size
      distribution and mean diameter of the sand. Various sands (average diameter
      ranging between 200 microm and 600 microm) were characterized and used as porous
      media. The structural parameters of the fixed beds were evaluated for each medium
      using experimental measurements of pressure drop as a function of superficial
      velocity over a range of Reynolds numbers covering Darcy's regime and the
      inertial regime. For a filtration cycle of six hours, the best efficiency (E =
      90%) was obtained with the following sand characteristics: sieved sand with a
      range of grain diameter of 100 and 300 microm and a mean grain diameter equal to
      256 microm. Results obtained show the influence of the size distribution of sand
      on the quality of retention of the micro-algae studied.

PMID- 22629643
TI  - Degradation of 2,4-dichlorophenoxyacetic acid by a halotolerant strain of
      Penicillium chrysogenum: antibiotic production.
AB  - The extensive use of pesticides in agriculture has prompted intensive research on
      chemical and biological methods in order to protect contamination of water and
      soil resources. In this paper the degradation of the pesticide 2,4
      dichlorophenoxyacetic acid by a Penicillium chrysogenum strain previously
      isolated from a salt mine was studied in batch cultures. Co-degradation of 2,4
      dichlorophenoxyacetic acid with additives such as sugar and intermediates of
      pesticide metabolism was also investigated. Penicillium chrysogenum in solid
      medium was able to grow at concentrations up to 1000 mg/L of 2,4
      dichlorophenoxyacetic acid (2,4-D) with sucrose. Meanwhile, supplementation of
      the solid medium with glucose and lactose led to fungal growth at concentrations
      up to 500 mg/L of herbicide. Batch cultures of 2,4-D at 100 mg/L were developed
      under aerobic conditions with the addition of glucose, lactose and sucrose,
      showing sucrose as the best additional carbon source. The 2,4-D removal was
      quantified by liquid chromatography. The fungus was able to use 2,4-D as the sole
      carbon and energy source under 0%, 2% and 5.9% NaCl. The greatest 2,4-D
      degradation efficiency was found using alpha-ketoglutarate and ascorbic acid as
      co-substrates under 2% NaCl at pH 7. Penicillin production was evaluated in
      submerged cultures by bioassay, and higher amounts of beta-lactam antibiotic were
      produced when the herbicide was alone. Taking into account the ability of P.
      chrysogenum CLONA2 to degrade aromatic compounds, this strain could be an
      interesting tool for 2,4-D herbicide remediation in saline environments.

PMID- 22629644
TI  - Fluorescence spectroscopy as a tool for determining microbial quality in potable
      water applications.
AB  - Building on previous work where fluorescence spectroscopy has been used to detect
      sewage in rivers, a portable LED spectrophotometer was used for the first time to
      establish bacterial numbers in a range of water samples. A mixed-method approach
      was used with standard bacteria enumeration techniques on diluted river water and
      sewage works final effluent using a number of diluents (Ringer's solution, tap
      water and potable spring water). Fluorescence from uncultured dilutions was
      detected at a 280 nm excitation/360 nm emission wavelength (corresponding to the
      region of tryptophan and indole fluorescence) and compared with bacteria numbers
      on the same cultured sample. Good correlations were obtained for total coliforms,
      E. coli and heterotrophic bacteria with the portable LED spectrophotometer (R2 =
      0.78, 0.72 and 0.81 respectively). The results indicate that the portable
      spectrophotometer could be applied to establish the quality of drinking water in
      areas of poor sanitation that are subject to faecal contamination, where
      infrastructure failure has occurred in the supply of clean drinking water. This
      would be particularly useful where laboratory facilities are not at hand.

PMID- 22629645
TI  - Biodegradation of 14C-dicofol in wastewater aerobic treatment and sludge
      anaerobic biodigestion.
AB  - Organic micropollutants are often found in domestic and industrial effluents.
      Thus, it is important to learn their fate, the metabolites generated and their
      sorption during biological treatment processes. This work investigated the
      biodegradation of 14C-dicofol organochloride during wastewater aerobic treatment
      and sludge anaerobic biodigestion. The performance of these processes was
      evaluated by physical-chemical parameters. Radioactivity levels were monitored in
      both treatments, and residues of dicofol (DCF) and dichlorobenzophenone (DBP)
      were quantified by HPLC/UV. The efficiency of the aerobic and anaerobic processes
      was slightly reduced in the presence of DCF and DBP. After aerobic treatment,
      only 0.1% of DCF was mineralized, and 57% of radioactivity remained sorbed on
      biological sludge as DBP. After 18 days of anaerobiosis, only 3% of DCF and 5% of
      DBP were detected in the sludge. However, 70% of radioactivity remained in the
      sludge, probably as other metabolites. Dicofol was biodegraded in the
      investigated process, but not mineralized.

PMID- 22629646
TI  - Achieving nitritation and anammox enrichment in a single moving-bed biofilm
      reactor treating reject water.
AB  - A biofilm with high nitrifying efficiency was converted into a nitritating and
      thereafter a nitritating-anammox biofilm in a moving-bed biofilm reactor at 26.5
      (+/- 0.5) degrees C by means of a combination of intermittent aeration, low
      dissolved oxygen concentration, low hydraulic retention time, free ammonia and
      furthermore, also by elevated HCO3- concentration. Nitrite-oxidizing bacteria
      (NOB) were more effectively suppressed by an enhanced HCO3- concentration range
      of 1200-2350 mg/L as opposed to free-ammonia-based process control where NOBs
      recovered from inhibition; the respective total-nitrogen removal rates were 0.3
      kg N/(m3 x d) and 0.2 kg N/(m3 x d). The biofilm modification strategies resulted
      in a shift in bacterial community as the NOB Nitrobacter spp. were replaced with
      NOB belonging to the genus Nitrospira spp. and were closely related to Candidatus
      Nitrospira defluvii. A community of anaerobic ammonium-oxidizing microorganisms 
      uncultured Planctomycetales bacterium clone P4 (closely related to Candidatus
      Brocadia fulgida)--was developed.

PMID- 22629647
TI  - Effects of coconut granular activated carbon pretreatment on membrane filtration
      in a gravitational driven process to improve drinking water quality.
AB  - This study evaluates the performance of a polymeric microfiltration membrane, as
      well as its combination with a coconut granular activated carbon (GAC)
      pretreatment, in a gravitational filtration module, to improve the quality of
      water destined to human consumption. The proposed membrane and adsorbent were
      thoroughly characterized using instrumental techniques, such as contact angle,
      Brunauer-Emmett-Teller) and Fourier transform infrared spectroscopy analyses. The
      applied processes (membrane and GAC + membrane) were evaluated regarding permeate
      flux, fouling percentage, pH and removal of Escherichia coli, colour, turbidity
      and free chlorine. The obtained results for filtrations with and without GAC
      pretreatment were similar in terms of water quality. GAC pretreatment ensured
      higher chlorine removals, as well as higher initial permeate fluxes. This system,
      applying GAC as a pretreatment and a gravitational driven membrane filtration,
      could be considered as an alternative point-of-use treatment for water destined
      for human consumption.

PMID- 22629648
TI  - Laboratory-scale evaluation of a combined soil amendment for the enhanced
      biodegradation of propylene glycol-based aircraft de-icing fluids.
AB  - A combined soil amendment was tested in microcosm experiments with an aim to
      enhance the aerobic biodegradation of propylene glycol (PG)-based aircraft de
      icing fluids during and following the infiltration of contaminated snowmelt. A
      key objective under field conditions is to increase degradation of organic
      pollutants in the surface soil where higher microbial activity and plant
      rhizosphere effects may contribute to a more efficient biodegradation of PG,
      compared to subsoil ground layers, where electron acceptors and nutrients are
      often depleted. Microcosm experiments were set up in Petri dishes using 50 g of
      soil mixed with appropriate additives. The samples contained an initial de-icing
      fluid concentration of 10,000 mg/kg soil. A combined amendment using calcium
      peroxide, activated carbon and 1 x Hoagland solution resulted in significantly
      higher degradation rates for PG both at 4 and 22 degrees C. Most probable numbers
      of bacteria capable of utilizing 10,000 mg/kg de-icing fluid as a sole carbon
      source were about two orders of magnitude higher in the amended soil samples
      compared to unamended controls at both temperatures. The elevated numbers of such
      bacteria in surface soil may be a source of cells transported to the subsoil by
      snowmelt infiltration. The near-surface application of amendments tested here may
      enhance the growth of plants and plant roots in the contaminated area, as well as
      microbes to be found at greater depth, and hence increase the degradation of a
      contaminant plume present in the ground.

PMID- 22629649
TI  - Management model for assessment of nitrogen flow from feed to pig manure after
      storage in Vietnam.
AB  - Nitrogen (N) losses from pig production and the recycling of N from manure to
      crops can harm the atmosphere, soil and ground water quality. This study intended
      to build a dynamic management model, adapted to the Vietnamese context, that
      links the N flow at all stages along the manure management chain from the N in
      the diets fed to grower-finisher pigs to the application of the manure in the
      field. The model assesses N contents and losses at each stage of manure
      management so that application of manure N can be adjusted to ensure optimal
      fertilizer value, while at the same time minimizing environmental damage. This
      model provides a tool for examining the N flow on pig farms, to adjust the N
      content of feeds, the pig population, and to minimize N discharge and emissions.
      The model is developed using Powersim software and data from feed-excretion,
      storage and composting experiments. For validation and performance of the model
      we used sub-datasets from feed-excretion experiments in Denmark and Vietnam that
      were not used to parameterize in the model. This article presents the development
      of the model and trial of the model through scenario analyses of pig production
      in livestock production zones. The objective is that policy makers, extension
      officers or agricultural advisors will use the model as a support management tool
      to formulate and adjust manure management practices. This includes assessment of
      the land carrying capacity in existing livestock production areas and of maximum
      acceptable manure loads in planned livestock production zones.

PMID- 22629675
TI  - The role of the social worker on the case management team.

PMID- 22629676
TI  - Acute care social work in today's environment.

PMID- 22629677
TI  - Collaborating on issues of non-compliance.

PMID- 22629678
TI  - [Diversity of acidophilic chemolithotrophic microbial consortia in natural and
      anthropogenic ecosystems].

PMID- 22629679
TI  - [Anaerobic oxidation of ammonia (anammox) in biofilms of immobilized activated
      silt in the process of wastewater purification with low concentration of
      contaminants].

PMID- 22629680
TI  - Investigation of unusual growth and phenotypic characteristics of plasmid
      containing and plasmid-free strains of oligotrophic bacterium Ancylobacter
      vacuolatus.
AB  - The oligotrophic bacterium Ancylobacter vacuolatus contains two large plasmids
      pREV1 and pREV2 (about 150 and 250 kb, respectively). Plasmid pREV1 carries the
      genes responsible for resistance to chloramphenicol, trimethoprim and y
      irradiation. Plasmid pREV2 carries the genes responsible for resistance to beta
      lactam antibiotics and formation of gas vacuoles. The ability to grow under
      oligotrophic conditions did not depend directly on either plasmid and was
      probably chromosome-encoded. Nevertheless, strains lacking the pREV2 plasmid had
      an improved capacity for growth in enriched media, as is evident from the
      following findings: 1) the growth rate of the strains lacking pREV2 was about 60%
      higher with an induction time of about two times less than those for strains
      carrying the plasmid; 2) the overall cell yield in rich media and colony size on
      non-oligotrophic agarized media increased with removal of pREV2; 3) the
      characteristic change in cell morphology occurring in the wild type ofA.
      vacuolatus when switched from oligotrophic to eutrophic growth conditions was not
      observed in the strains lacking pREV2; 4) bacterial strains lacking pREV2
      exhibited significantly higher rRNA content than the parent strain. As a possible
      explanation for these phenomena, we suggest that the pREV2 plasmid carries
      gene(s) for protein(s) acting as repressor(s) of expression of some enzymes
      involved in eutrophic metabolism. Such protein(s) probably participate in
      switching between the oligotrophic and eutrophic types of metabolism in response
      to changing nutrient supply in the environment.

PMID- 22629681
TI  - [Biodegradation of glyphosate by soil bacteria: optimization of culture and
      method for active biomass preservation].

PMID- 22629682
TI  - [Acidobacteria in microbial consortia of wetlands and tundra lichens].

PMID- 22629683
TI  - [Hoeflea siderophila sp. Nov., new neutrophilic iron-oxidizing bacteria].

PMID- 22629684
TI  - [Isolation of Variovorax genus bacteria from Thioploca colonies of lake Baikal].

PMID- 22629685
TI  - [Sulfate reduction, formation and oxidation of methane in Holocene era sediments
      of the Vyborg Bay, Baltic Sea].

PMID- 22629686
TI  - [Microbial consortia of neutrophilic iron-oxidizing organisms from iron sources
      of different origins and their role in fractionation of stable iron isotopes].

PMID- 22629688
TI  - [Mycobiota of giant oyster, Crassostrea gigas (Thunberg, 1787) (Bivalvia), from
      the Peter the Great Bay, Sea of Japan].

PMID- 22629687
TI  - [Thermotolerant and thermophilic soil Actinomycetes from desert steppes of
      Mongolia].

PMID- 22629689
TI  - [Method for bacterial sensitivity determination towards barium ions - taxonomic
      marker of Pseudomonas genus].

PMID- 22629691
TI  - [On the 50th anniversary of the introduction into clinical practice of flexible
      endoscopy. Steps and prospects of development of endoscopy of gastrointestinal
      tract].

PMID- 22629690
TI  - [New morphotypes of condensed DNA microparticles formed in PCR with KlenTaq- and
      Taq-polymerases and with plasmid DNAs as templates].

PMID- 22629692
TI  - [The frequency of anemia among patients of gastroenterological hospital].
AB  - The article analyzes the prevalence of anemia among 18 800 patients treated at
      the CSRI of Gastroenterology in 2-year observation. Set the frequency of anemia,
      which was 8.63%, clarified the influence of gender and age on the frequency of
      anemia. Characteristics of anemia severity, morphological changes of
      erythrocytes. Highlights the major disease entities: cirrhosis, PBC, IBD, celiac
      disease tumors in the organs of the gastrointestinal tract, threatening the
      development of anemia.

PMID- 22629693
TI  - [Risk of development of clinical and pathogenetic features of anemia on the
      background of basic therapy of inflammatory bowel disease].
AB  - Anemia in IBD is the result of a combination of iron deficiency and anemia of
      chronic disease. Therapy of IBD is relief of inflammation, but the drugs usage
      may cause the development hemolytic anemia and myelodysplastic syndrome. We
      studied the effect of basic therapy on the incidence of anemia and assess the
      impact of modern biological therapies on the main markers of AHZ. A total of 153
      patients with ulcerative colitis (UC) and 53 patients with Crohn's disease (CD),
      which at the time of the study received basic anti-inflammatory therapy for at
      least 1 year. All patients underwent blood tests, iron metabolism parameters were
      determined by the level of erythropoietin and G-gepsidina C reactive protein.
      Modern biological therapy increases the effectiveness of the treatment of anemia
      in patients with IBD. The use of Remicade gives a quick positive response, which
      is due to the decrease of gepsidin negative influence on iron metabolism and
      unlocking the synthesis of erythropoietin. The use of MSCs does not inhibit the
      synthesis of erythropoietin, and is likely to stimulate erythropoiesis at the
      erythroblast precursors.

PMID- 22629694
TI  - [Clinical and diagnostic significance of gepsidin level in the regulation of iron
      metabolism in patients with inflammatory bowel disease].
AB  - Gepsidin is an iron regulatory protein that inhibits ferroportin, limiting the
      transport of iron into the cell of the small intestine villi and blocking the
      exit of iron from macrophages, that often leads to disruption of iron
      homeostasis, iron deficiency and the development of anemia. The Aim was to study
      the levels of gepsidin in patients with IBD and determine its prognostic
      significance for the development of anemia. We examined 80 patients with IBD, 45
      (56%) men and 35 (44%) women with the average age of 39,0 +/- 15,8 years. In 40
      patients with anemia and 40 patients with IBD without anemia syndrome, studies
      were conducted in the status of iron metabolism, the level of gepsidin, TNF, C
      reactive protein. CONCLUSION: IBD with systemic inflammatory response leads to
      increased levels gepsidina and increases the risk of anemia in IBD. Determination
      of gepsidin in IBD patients enables identify patients at risk for anemia and to
      clarify the effectiveness of the basic treatment of the disease.

PMID- 22629695
TI  - [Replicative activity of hepatitis B as a factor determining the progression of
      liver fibrosis and cirrhosis].

PMID- 22629696
TI  - [Syndrome of iron overload and its impact on the clinical course and risk of
      complications in patients with liver cirrhosis].
AB  - The paper presents the results of a study of iron metabolism in 185 patients with
      cirrhosis of different etiologies. The frequency of iron deficiency in 28.6% of
      patients and the syndrome of iron overload - 18.9%. The gender and etiology of
      cirrhosis role in the frequency of occurrence of the syndrome of iron overload
      and iron deficiency. The iron metabolism disorders in relationship with the
      frequency of complicated cirrhosis, the severity of liver cirrhosis, according to
      Child-Pugh's grade of severity of liver disease, the severity of cytolytic
      syndrome.

PMID- 22629697
TI  - [Pharmacokinetics of iron medication and efficacy of therapy with oral iron
      supplementation].
AB  - The pharmacokinetics of iron oral medication in was studied in patients with
      liver cirhorosis. In patients with hepatocellular insufficiency and high level of
      gepsidin found a decrease of the iron absorption constant, which led to a change
      in pharmacokinetic parameters. Tests on the absorption of iron have been
      conducted in 25 patients with liver cirrhosis, 36% of them showed a decrease of
      iron absorption, which led to the decrease in the efficiency of subsequent iron
      therapy. Found that elevated levels of gepsidin that lead to violation of iron
      metabolism and absorption and reduce the effectiveness of the treatment of iron
      deficiency.

PMID- 22629698
TI  - [Deficiency of essential microelements in patients with diseases of the digestive
      system].

PMID- 22629699
TI  - [Bone mineral density infringement in patients with digestive system diseases].
AB  - THE AIMS: To develop criteria for prediction of disorders of bone metabolism and
      improve prevention and treatment of osteopenia in gastroenterological patients on
      the basis of pathogenic features of its development. Recent literature data show
      that a number of digestive diseases exacerbate the risk of
      osteopenia/osteoporosis in patients with population risk factors. Reduced bone
      mineral density in patients with certain diseases of the digestive system occurs
      equally in both cortical and trabecular bone tissue, indicating the polyetiology
      osteopenia in this group of patients.

PMID- 22629700
TI  - [The experience of modern methods of enteroscopy in the diagnosis of Crohn's
      disease].
AB  - The aim of the study is to evaluate the possibilities of videocapsule endoscopy
      (VCE), single and double balloon enteroscopy in diagnosis of small bowel Crohn's
      disease. MATERIAL AND METHODS: From V.2003 to IV.2011 we observed 52 pts. with
      suspected small bowel Crohn's disease; 8 (15.4%) of them were operated urgently
      because of complications. Another 44 pts (m-23, f-21, ranged from 15-72 years,
      mean age 37.5 +/- 12.0 years) underwent complex examination including 19 VCE and
      49 BAE in 32 pts.(incl. 7 after VCE). RESULTS: Typical Crohn's disease appearance
      was found in 15 (34.1%) pts (incl. 4pts after VCE) from 44 who were examined
      endoscopically. In 8 pts we've revealed stenosis, in 4 of them we've passed
      through the ileocecal valve stenosis by bouginage with the enteroscope and were
      able to examine superior area. After performing target biopsy from the small
      bowel mucosal lesions Pirogov - Langhans cells were found in 5 (33.3%) pts. We
      haven't found any signs of Crohn's disease in 17 pts. (no abnormalities found-6,
      enteritis-9, celiac disease-1, NSAID-ulcers-1). Conservative treatment has been
      applied in 10 (66.7%) pts., surgical intervention - in 5 (33.3%) pts. There was a
      capsule retention in 2 (10.5%) pts. There were no any complications in BAE.
      CONCLUSION; The use of the new enteroscopic techniques substantially improves the
      diagnosis of small bowel

PMID- 22629701
TI  - [Methods to stop and to prevent bleeding in patients with varicose veins of
      esophagus and stomach].

PMID- 22629702
TI  - [Transesophageal ultrasonography in the diagnosis of malignant tumors of the
      mediastinum].
AB  - AIM: To assess transesophageal ultrasonography capabilities in diagnosis of
      mediastinal malignant tumors. MATERIALS AND METHODS: Technique of radial
      transesophageal ultrasonography was used to diagnose mediastinal malignancy in
      157 patients. Method of amplitude hystography was employed to assess lymph nodes.
      In 84 cases diagnosis had histological confirmation. RESULTS: In 61 case out of
      84 (73%) diagnosis was true. In of lymph nodes without primary tumor in the lung
      diagnosis was true in 72% (26 cases out of 36) and with primary tumor in 73% (35
      cases out of 48). Assessment of lymph nodes sized 30 mm and more was correct in
      92% (11 cases out of 12) and much higher than for lymph nodes sized less 30 mm in
      diameter (69%, 50 out of 72 [p < 0.001, chi2]). Correct diagnosis for lymph nodes
      less than 10 mm in diameter was achieved in 65% (13 out of 20) [p = 0.44, chi2],
      for diameter 10-20 mm accuracy was 71% (22 cases out of 31) [p = 0.96, chi2] and
      similar to the one for diameter 20-30 mm assessment. Location of lesion proved to
      be important. For lymph nodes of 3, 7, 8, 9 zones (ATS classification) precision
      was much higher than for other locations. There were no adverse events during the
      study. CONCLUSION: Transesophageal ultrasonography with the use electronic radial
      detector is effective an safe method of mediastinal lymph nodes and primary
      tumors assessment.

PMID- 22629703
TI  - [The results of endoscopic mucosal resection and submucosal layer endoscopic
      dissection in patients with superficial epithelial neoplasms of stomach and
      duodenum].
AB  - AIM OF STUDY: Comparative assessment outcomes of endoscopic mucosal resection
      (EMR) and endoscopic submucosal dissection (ESD) in patients with superficial
      epithelial lesions (SEL) of stomach and duodenum. MATERIALS AND METHODS:
      Retrospective study includes 92 patients. The article contains detailed
      description of patients, superficial epithelial lesions, technique of EMR and ESD
      and indications for endoscopic procedure. RESULTS: 99 endoscopic operations were
      performed: EMR--79, ESD--20. The mean operation time, en bloc resection rate,
      complete resection rate for early gastric cancer were assessed for EMR and ESD
      and compared in consideration of lesion's size. Comparative evaluation of
      immediate, short-term and long-term outcomes of endoscopic resections was
      performed. CONCLUSION: ESD provides better en bloc and complete resection rates
      and minimal local recurrence compared with EMR, but ESD is more time-consuming
      technique with the same rate of complications.

PMID- 22629704
TI  - [New technologies in the diagnosis and treatment of patients with squamous cell
      carcinoma of the anal canal].
AB  - PURPOSE OF THE STUDY: The development of the rectum preservation treatment for
      the squamous-cell carcinoma of the anal canal. MATERIALS AND METHODS: The
      following scheme of the rectum preservation treatment for the squamous-cell
      carcinoma of the anal canal was developed and has been used in the Cancer
      Research Center RAMS since 1995. The irradiation is performed to the small
      pelvis, perineum and ilioinguinal lymph nodes, at a single dose 2 Gy, 22
      sessions, total dose 44 Gy. Radiotherapy is associated with chemotherapy:
      cisplatin 20 mg/m2, twice a week, No 8; bleomycin 15 mg, twice a week, No 8.
      Irradiation is combined with 4-5 sessions of local hyperthermia. Local
      hyperthermia (about 42.5-43 degrees C in the tumor) was given for 60 minutes
      after irradiation. Local hyperthermia increases the effect of chemoradiotherapy
      in 1.5-2 times. If the tumor resorbtion exceeds 75%, intrarectal irradiation is
      performed at a single dose 3 Gy, 7-8 sessions, total dose 21-24 Gy. If the tumor
      resorbtion is less than 75%, abdomino-perineal resection is performed. RESULTS:
      This scheme was used in the treatment of 92 patients, rectum preservation
      treatment was performed in 76 cases (83%), abdomino-perineal resection--in 16
      cases (17%). Local recurrences were in 10.0%, the overall 5-year survival was
      75.2 +/- 8.5%.

PMID- 22629705
TI  - [Radiological diagnosis of liver hemangiomas: look at the problem of surgical
      clinic].
AB  - AIM: To define significance of radiological diagnostics in detection and
      characterization of hepatic hemangiomas. MATERIALS AND METHODS: Analysis of 176
      patients with liver hemangiomas was performed. All patients were investigated or
      consulted in hepato-pancreato-biliary surgical department. US, CT, MRI,
      angiography, scintigraphy and liver biopsy were compared. RESULTS: Contemporary
      noninvasive diagnostics disclose liver hemangiomas with high confidence without
      need for tumor biopsy. MRI and CT with intravenous enhancement are the most
      efficient modalities for detection of hepatic hemangiomas.

PMID- 22629706
TI  - [Effect of pancreatic secretory trypsin gene mutations on the development of
      chronic pancreatitis].
AB  - For the first time the relationship between mutations in the pancreatic secretory
      trypsin inhibitor (SPINK1) in humans and the development of chronic pancreatitis
      was established in 2000. By mid 2011 the number of studies on the influence of
      SPINK1 gene mutations on the development of pancreatitis exceeds 250, the results
      vary greatly. According to modern concepts, mutations in SPINK1 gene are
      associated with the development of both acute and chronic pancreatitis, and are
      defined in all etiological forms. Literature review shows the data of the most
      significant studies about the role of SPINK1 gene mutations in pancreatic
      diseases.

PMID- 22629707
TI  - [Gastric carcinoid--modern approaches to diagnosis and treatment].
AB  - Gastric carcinoid tumors are rare, but are increasing in incidence. This article
      reviews what is known about the classification, epidemiology, tumor pathogenesis
      and management of patients. Additionally we present the results of our own 10
      years observation after endoscopic and surgery treatment of this tumors.

PMID- 22629708
TI  - [Challenges and opportunities for endoscopic ultrasound in the preoperative
      diagnosis of topical insulin the pancreas].
AB  - Insulinoma in most cases is monohormonal orthoendocrine tumor. This fact limits
      its searching area by a pancreas. However the insulinoma's clinical picture can
      be caused by other pathology. Therefore the main task of visual the tumor but
      also to use all the possibilities of each method for defining type of surgery and
      avoiding such errors and complications, as pancreatorrhage, damage of bile or
      pancreatic duct, necrosis of duodenal wall, etc. On the basis of our own
      experience of endoscopic ultrasound for 61 patients with 66 insulinomas, we have
      allocated the basic variants of insulinoma ultrasound pictures: hypoechoic,
      heteroechoic, isoechoic tumor, and also foci without a trustworthy contour. On
      the basis of the analysis of our own errors we have essentially added the
      technique, having used multiplane pancreas scanning and biplane tumor scanning.
      Important points in EUS algorithm are also the following items: detecting tumor
      relationship to pancreatic surface, distance from the tumor to the ducts,
      gastrointestinal wall and vessels--for definition of possibility of the tumor
      enucleation; careful scanning of pancreas even after detecting one tumor--for an
      exception of multiple tumors, especially at MEN-I; careful scanning of a contour
      of the gland for an exception of parapancreatic insulinomas; estimation of
      vascularization not only of the detected tumor and suspicious foci, but also of
      all the gland--for detection of hypervascularized isoechoic tumors; revealing and
      the description of focal changes, especially more homoechogeneous in comparison
      with surrounding parenchyma-- for selection patients for examination by other
      methods; scanning of zones of possible metastasis. Examination of patients with
      organic hyperinsulinism demands combined application of two or more techniques.
      Use of all modern possibilities of endosonography can put this technique on one
      of the first places in the diagnosis of insulinomas.

PMID- 22629709
TI  - [Modern aspects of photodynamic therapy of esophageal].
AB  - This review presents the current possibilities of photodynamic therapy in the
      treatment of precancerous lesions and cancer of the esophagus. Mechanisms of
      photodynamic effects on tumor and especially the accumulation of photosensitizer
      in tumor tissue, results of studies on the use of photodynamic therapy in the
      treatment of early esophageal cancer, esophageal cancer stenosis and combinations
      with other treatment techniques. Results of treatment of Barrett's esophagus
      using photodynamic therapy were analyzed and a compared with other methods of
      treatment.

PMID- 22629710
TI  - [Abdominal pain attacks and diarrhea disorders due to an internal stent draining
      of left kidney in a patient with a cascade stomach].

PMID- 22629711
TI  - [Inflammatory bowel disease: Oxford Masterclass 2011].

PMID- 22629712
TI  - [Atherosclerosis is the disease of hepatocyte].

PMID- 22629713
TI  - [Obesity is new noninfectious "epidemic"].
AB  - The widespread obesity and its complications is the reason for ongoing research
      of obesity trigger mechanisms, effective and safe methods of treatment and
      prevention. In the present paper we use the literature data devoted to the study
      of the pathogenesis of obesity, its diagnosis and treatment over the past 15
      years. Currently, emphasis is placed on finding and developing new integrated
      programs of treatment and rehabilitation of patients with this pathology.

PMID- 22629714
TI  - [Endotoxin (LPS) in the pathogenesis of atherosclerosis].
AB  - Recent data on the processes underlying atherogenesis indicate the significant
      role of endotoxin (lipopolysaccharide - LPS) of the intestinal microflora in the
      development of vascular lesions. This paper summarizes the literature and
      material results of their research on the participation of LPS gramnegativnyh
      bacteria in the initiation and progression of atherosclerosis. We prove that the
      LPS of gram-negative bacteria interact with TLR4, triggers cytokine cascade with
      the subsequent formation of atheroma.

PMID- 22629715
TI  - [Quality of life in chronic pancreatitis patients with metabolic syndrome (M
      Annheim classification)].
AB  - Among 81 patients with chronic pancreatitis (CP) metabolic syndrome (MS)
      diagnosed in 51.8% of persons; the frequency of MS in possible, probable and
      definite forms of CP, and well as in various of index of CP severity (A, B, C, D)
      did not differ. Average of QOL in all the examined patients with CP, assessed by
      SF-36 questionnaire, were: the scale of FF--47.2 +/- 3.6; RF--8.3 +/- 3.3; BP-
      37.4 +/- 2.3; GH--33.7 +/- 2.1; V--46.5 +/- 1.7; SF--65.0 +/- 2.7; REF--10.0 +/-
      3.7; MH--59.9 +/- 1.9. Mean QoL in CP patients, assessed by questionnaire GIQLI,
      were: on a scale of symptoms (C)--41.8 +/- 2.0; emotions (E)--8.3 +/- 0.6;
      physical functioning (PF) - 10.0 +/- 1.0; treatment (T)--3.8 +/- 0.1; social
      functioning (SF)--10.6 +/- 0.4; the total score (TS)--74.4 +/- 3.3. QoL in
      patients with biliary, alcoholic or idiopathic etiology of CP did not differ
      neither by SF-36, nor by GIQLI. In CP patients with MS QoL in the scales RFF, GH
      and REF by SF-36 questionnaire and in the scales of E, TS by questionnaire GIQLI
      were significantly better than in CP patients without MS.

PMID- 22629716
TI  - [Differentiated approaches to the treatment of chronic pancreatitis patients with
      metabolic syndrome].
AB  - AIM: study and evaluation of clinical efficacy of combined use of Creon and
      Tricor in chronic pancreatitis (CP) accompanied by metabolic syndrome (MS).
      MATERIALS AND METHODS: We observed 60 patients with CP accompanied by MS, of whom
      30 patients received standard therapy complex CPs (comparison group), 30-
      received Creon (microspheres of pancreatin) and Tricor (fenofibrate) in the
      combined treatment (observation group). In assessing the effectiveness of
      therapies used in clinical and advanced laboratory and instrumental studies.
      RESULTS: In the course of treatment in patients with the observation group
      occurred faster clinical improvement, improved lipid, carbohydrate and purine
      exchange and decreased insulin resistance. CONCLUSION: The combined use of Creon
      and Tricor is pathogenetically substantiated and clinically effective in the CP
      accompanied by MS.

PMID- 22629717
TI  - [The role of hormones and types of food behavior in the pathogenesis and
      treatment of abdominal obesity].
AB  - Hormones and the types of eating behavior play the leading role in the
      development and progression of abdominal obesity. Based on the evaluation of the
      dynamics of hormones EB and modification of EB types on background of the
      treatment can determined the most effective method for correction of body weight,
      which allows not only to achieve the desired result in the short-term, but also
      to keep the result for a long time.

PMID- 22629718
TI  - [Metabolic syndrome and nonalcoholic fatty liver diseases in children].
AB  - The review of literature considers the problem of the metabolic syndrome and
      nonalcoholic fatty liver disease in children. It provides information about
      common pathogenesis of the metabolic syndrome and nonalcoholic fatty liver
      disease, the relationship of diagnosis and treatment.

PMID- 22629719
TI  - [Dynamics of serum IL-17A, IL-17F and IL-23 in patients with inflammatory bowel
      disease].
AB  - The analysis of the levels of proinflammatory cytokines IL-17A, IL-17F and IL-23
      allow to evaluate the effectiveness of the therapy:, so MSCs systemic
      immunosuppressive therapy and corticosteroids increasingly reduces the level of
      all studied proinflammatory cytokines, while in therapy with infliximab, a
      selective immunosuppressive agent, significantly less effect on the level of
      proinflammatory cytokines IL-17A, IL-17F and IL-23.

PMID- 22629720
TI  - [The therapeutic effect of pollen and perge in malnutrition, metabolic syndrome
      and hepatitis unspecified etiology].

PMID- 22629721
TI  - [The role of the population risk factors in the genesis of osteo metabolism in
      patients with chronic diseases of the digestive system].
AB  - The paper presents the results of a study of bone mineral density in patients
      with various chronic diseases of the digestive system. Studied the value of the
      known population risk factors such as female gender, menopause in women,
      decreased body mass index, age, and in the genesis of osteopenia and/or
      osteoporosis in gastroenterological patients.

PMID- 22629722
TI  - [Electrophysiological research method of digestive tract].
AB  - Investigation of electromotor activity of smooth muscle in diseases of the
      gastrointestinal tract is a modern electrophysiological method to determine the
      motor disorders of the digestive tract before, during and after therapy. Non
      invasive method allows its repeated use in difficult diagnostic cases.

PMID- 22629723
TI  - [Pancreas and metabolic syndrome].
AB  - The functional state of the pancreas has a significant share in the development
      of the basic components of MS (hyperinsulinemia, insulin resistance, impaired
      glucose tolerance) and, conversely, the existing metabolic changes (obesity,
      atherogenic dyslipidemia) contribute to the violation of the endocrine and
      exocrine pancreatic function. It is assumed, on the one hand, the fundamental
      role of fatty pancreas disease in developing metabolic syndrome, with the
      formation of insulin resistance, on the other hand, indicates that
      hyperinsulinemia, hyperglycemia and dyslipidemia, as well as microcirculatory
      disturbances aggravate the state of the pancreas. Trigger mechanism of
      progression pancreatic pathology in MS appears inflammation closely accompanied
      with fatty infiltration of the body against obesity. Changes in pancreas specific
      to MS, are not only secondary to its background, but also contribute to the
      progression of the syndrome and the development of complications, closing the
      pathogenic circle.

PMID- 22629724
TI  - [Role of modified lipoprotein in the development of atherogenic dyslipidaemia].
AB  - In process and progression of atherosclerosis top-ranked spot belongs to
      Atherogenic dyslipidemia. This contribution presents analysis of job related to
      role of lipoproteins in process of dyslipidemia over the past 15 years.

PMID- 22629725
TI  - [UDCA in the treatment of nonalcoholic fatty liver disease].
AB  - As a signaling molecule with system endocrine function, UDCA improves insulin
      sensitivity by activating the nuclear farnezoid X-receptor; as a ligand for the
      TGR5/Gpbar-1 receptor, UDCA is able to stimulate the secretion of GLP-1. UDCA
      ameliorate of the anti-oxidative defenses in NAFLD, normalizes NAD+/NADH ratio,
      beta-oxidation. UDCA improves the liver biochemical and histological picture in
      NASH, also reduces hepatocytes apoptosis and restores adiponectin levels; in
      other studies, these data are not confirmed. In the experiment, UDCA prevents the
      development of steatosis in the liver. UDCA may increase efficiency in
      combination with statins, thiazolidinediones, vitamin E. Further controlled
      prospective trials are needed for research of the UDCA effect in NAFLD.

PMID- 22629726
TI  - [Complications after gastric-bypass surgery for morbid obesity].
AB  - The use of conservative methods of treatment of obesity shows that decrease in
      body weight is accompanied by improvement of general condition, and a significant
      positive effect in essential types of metabolism, in particular, helps to reduce
      the frequency of diabetes type II and other components of the metabolic syndrome.
      However, to achieve sustained weight loss in patients with morbid obesity, using
      only conservative treatment is almost impossible. In connection with what
      clinicians have actively solve this issue, including the surgical treatment.
      Surgical treatment of obesity are shown in patients with third degree obesity
      (BMI > or = 40), when there is no result from long-term treatment diets and other
      therapeutic methods. Along with the positive effect that manifests itself in
      rapid weight loss, normalization of lipids and blood glucose, these
      interventions, particularly bypass, are characterized by specific complications,
      which can be fatal to patients. The most common of them, apart from surgical
      (anastomotic stenosis, infection, etc) are: malabsorption syndrome, and dumping
      syndrome. Exactly these complications are presented in the description of the
      case.

PMID- 22629727
TI  - [Difficulties in vivo diagnosis of mucinous adenocarcinoma of vermiform appendix
      with metastasis in the navel].
AB  - The article presents a clinical case of mucinous adenocarcinoma in vivo diagnosis
      of vermiform appendix with metastasis in the navel. Neoplasms vermiform appendix-
      an extremely rare tumor pathology: the total share of all malignant tumors are
      less than 1%. Mucinous carcinoma is a rare tumor, according to various authors
      the frequency of its occurrence ranges from 3 to 10% of all malignancies. By
      Localization mucinous carcinoma more frequently is found in the colon and rectum
      (about 20% of cases), ovary (5-10% of all malignant ovarian tumors), stomach,
      uterus and also in the pancreas (only about 2%). Metastasis in the navel is a
      very rare disease and is known as Sister Mary Joseph's Nodule, the primary site
      often localized in the digestive tract (52%), much less--in the female
      reproductive organs (28%), unspecified localization is approximately 15-20% of
      cases. The difficulty of diagnosis in the present case was that, in spite of life
      conducted during survey of the colon, organic pathology was not identified. The
      presence of hepatosplenomegaly and ascites at the initial examination gave cause
      to the erroneous diagnostic conception of the presence of liver cirrhosis. It is
      also was not paid due attention to the presence of changes in the umbilical ring,
      which were regarded as an umbilical hernia. To verify the diagnosis allowed the
      infiltrate biopsy of the umbilical region, followed by histological examination
      of the preparation and identification of a characteristic picture of mucinous
      cancers.

PMID- 22629728
TI  - [Colorectal cancer in women: screening and prevention in 2011].

PMID- 22629729
TI  - [Dmitry Pletnev--doctor, scientist, teacher (by the140-anniversary of birthday)].

PMID- 22629730
TI  - [Contribution of M. Lomonosov in the development (by the 300th anniversary of
      Lomonosov's birthday) medicine in Russia].

PMID- 22629731
TI  - [The state of the vascular bed of the small intestine in patients with portal
      hypertension].
AB  - AIM: To evaluate the condition of vascular channel of small bowel in patients
      with portal hypertension. MATERIALS AND METHODS: We examined 60 patients from 17
      to 70 years, 30 with cirrhosis of different etiologies and 30 with other
      gastrointestinal diseases, amounted control group. Patients were divided into 2
      groups: the main and control: group 1--primary--patients with cirrhosis and
      portal hypertension. Group 2--control--patients without liver disease and portal
      hypertension who underwent videocapsule endoscopy. RESULTS: On the results of
      research, we can conclude that all patients with liver cirrhosis and portal
      hypertension have various vascular changes of small bowel. We examined patients
      in the course of the work revealed the following: 1. Varicose vein expansion and
      increased vascular pattern in 70% of patients. 2. Arteriovenous malformation in
      12% of patients. 3. Angiodisplaziya 11%. 4. Delafua defect in 4%. 5. Bleeding in
      3%. The combination of vascular disease in patients with liver disease and portal
      hypertension syndrome accounted for 70%. In the control group of patients
      vascular channel pathology dated only in 2% of cases in the form of strengthening
      of vascular pattern of small bowel. CONCLUSION: Videocapsule endoscopy is a
      highly informative diagnostic method for assessing the condition of vascular
      channel of the intestine in patients with portal hypertension. Carrying out
      videocapsule endoscopy is highly effective and comfortable for patients, which
      greatly improves their quality of life. Timely detection of vascular disease in
      patients with portal hypertension using videocapsule endoscopy can prevent such
      severe complications as gastrointestinal bleeding especially from the deep
      divisions of bowel which are not available to other research methods.

PMID- 22629732
TI  - [Antibodies to infliximab and antigens HLA I-II class as the witnesses of immune
      response to the biological treatment of inflammatory bowel disease].
AB  - Despite combination therapy with immunosuppressive agents, 32.5% of patients with
      IBD showed the formation of antibodies to infliximab. Simultaneous study of the
      concentration of the drug (infliximab), TNF-alpha and antibodies to it in the
      blood serum allows to judge not only on the effectiveness of anticytokine
      therapy, but also on the advisability of further conducting therapy. Elevated
      levels of AINF may lead to infusion reactions, reducing the effectiveness and
      duration of response to this therapy. Transplantation of MSCs reduces the level
      of antibodies to infliximab, but in 2 (5%) patients noticed a gradual increase of
      these antibodies. After infliximab infusion from 4 to 8 weeks the level in serum
      increased up to 45 mg/ml and higher, further serological concentration of
      infliximab is gradually reduced and then falls below the-horn. High
      concentrations of infliximab (> 45 mkg/ml) in blood samples at combined
      immunosuppressive therapy (infliximab + glucocorticoids + cytotoxic agents)
      should be considered as a sign of potential complications. The absence of
      antibodies to antigens of HLA I and class II after systemic transplantation of
      allogeneic mesenchymal stromal cells (MSCs) of bone marrow demonstrates not only
      the effectiveness but also the safety of transplantation of allogeneic MSCs, in
      relation with that the special selection of donors for transplantation of
      allogeneic MSCs is not required.

PMID- 22629733
TI  - [The method of radiographic examination anorectal area].
AB  - PURPOSE: Puborectal muscle (PRM) plays an important role in the continence. Its
      function is impaired in chronic constipation, fecal incontinence, especially
      after anorectal surgery. Assessment of PRM condition by the measurement of
      anorectal angle is not precise, the defecography requires special equipment and
      is associated with high doses of radiation. The purpose of this study is to
      propose another method of evaluation of anorectal function free of the above
      mentioned disadvantages. MATERIAL AND METHODS: The analysis of 475 studies of
      patients of all ages, including 79 without pathology anorectal area and 396
      patients with different pathologies was done. They were examined by a method that
      differs from the usual barium enema by placing of radiopaque marker near the
      anus. RESULTS AND DISCUSSION: The weakness of PRM manifested by penetration of
      barium into the anal canal behind the tip of the enema. The prominent shortening
      of the anal canal, compared to age-related normal figures indicates the PRM
      failure. The finding of the anal canal shortening has the same diagnostic value
      as the perineum distendion revealed by defecography. The proposed method is
      simple, accurate, and does not apply large dose of radiation.

PMID- 22629734
TI  - [Calcium-phosphorus ratio in relapse of peptic ulcer disease].
AB  - AIM: To determine the metabolism of calcium and phosphorus in the period of
      peptic ulcer recurrence and to compare it with gastric secretion and motility.
      MATERIALS AND METHODS: 150 patients with peptic ulcer recurrence were examined.
      Apart from clinical and endoscopic examinations, the presence of calcium and
      phosphorus in blood and urine was detected, gastric secretion and motility were
      determined. RESULTS: It was ascertained that recurrence of peptic ulcer was
      accompanied by essential increasing of calcium and decreasing phosphorus in
      blood, insignificant hypercalciuria and hyperphosphaturia. These changes were
      accompanied by considerable increasing of gastric secretional function,
      decreasing production of gastromucoproteids and gastric hypermotility. The more
      significant changes of calcium-phosphorus metabolism were determined in the acute
      phase of the recurrence in duodenal ulcers in young males. CONCLUSION: The
      evident connection between the impairment of calcium and phosphorus metabolism,
      the activity of peptic ulcer and changes in the function of stomach can show the
      importance of these changes in pathogenesis of ulcer and the validity of
      therapeutic correction of these changes in case of the recurrence.

PMID- 22629735
TI  - [Mechanisms of formation and substantiation of pathogenetic treatment of the long
      term non-cicatrizing gastroduodenal ulcers].
AB  - 162 patients with a stomach ulcer were examined, 98 people were with torpid
      course of a stomach ulcer, and 64 sick people were usual periods of cicatrizing
      ulcers. 56 sick people (the first group) with torpid course of a stomach ulcer
      received immunal as a part of complex irradical therapy and comparising group 42
      sick people (the second group) with torpid course used only irradical therapy. In
      estimation of efficiency of therapy, in addition to clinical and endoscopies
      data, indicators of genotypes Helicobacter pylori and immune system were used.
      The pathogenetic role of virulent genotypes Helicobacter pylori in the formation
      of the torpid course of a stomach disease is shown. The information about the
      dependence of the immune defense from cytotoxic characteristics Helicobacter
      pylori was received. Inclusion of immunal in complex therapy improves the
      elimination of Helicobacter pylori and has good clinical effect.

PMID- 22629736
TI  - [Patients rehabilitation in a day-time hospital after surgical management of
      complications of peptic ulcer].

PMID- 22629737
TI  - [The relationship of clinical and morphological characteristics of chronic
      gastritis with microelements deficiency].
AB  - We aimed to analyze the interconnection of chronic gastritis clinicopathologic
      characteristics with the content of selenium, zinc and manganese in blood serum.
      It is stated that the concentration of the microelements being studied (mostly
      selenium) is the prognostic indication of prescription of inflammatory process in
      the mucous coat of stomach and its clinical activity (pain and dyspeptic syndrome
      intensity), and the degree of microelements deficiency increases proportionally
      with intensity augmentation of atrophic processes in stomach.

PMID- 22629738
TI  - [The selenium, zinc and manganese content in the serum of patients with various
      types of chronic gastritis in the Chuvash Republic].

PMID- 22629739
TI  - [Peculiarities of stress erosive ulcerous injuries of stomach and small
      intestine].
AB  - AIM: The aim of this investigation is to estimate the role of systemic injuries
      of lipid metabolism in pathogenesis of ulceration on the model of stress
      ulcerogenesis. MATERIALS AND METHODS: There have been assumed as a basis of the
      work experimental investigations on 60 pubertal white rats of both sexes weighing
      200 gr. There was studied the state of macroscopic picture of stomach and small
      intestine, qualitative and quantitative lipid composition, lipid peroxidation,
      phospholipase A2, catalase, superoxide dismutase in stomach tissues, small
      intestine and blood plasma. RESULTS: The facts of the experimental investigations
      show, that by the effect of ulceration stress there are processes, that underlie
      modifications of lipid components of cell structures' biomembranes, and
      registered by qualitative and quantitative changes of lipid composition.
      Intensification of lipid peroxidation and activation of phospholipase A2 are the
      key mechanisms of qualitative and quantitative composition of biomembranes' lipid
      components, and they reduce to beginnings of cascade of pathomorphological and
      pathophysiological reactions in cell structures, which cause beginnings of
      membrane destructive processes, that is as a basis of ulcerogenesis. CONCLUSION:
      In the result there is broken morphofunctional state of mucous membrane (one of
      the main factors of protection), that in the end makes it accessible substratum
      for other aggressive factors and promotes the formation of ulcerous defects.

PMID- 22629740
TI  - [Postoperative lesions of the gastrointestinal tract--actual problem of modern
      urology].
AB  - THE AIM: To study the prevalence of diseases of the upper gastrointestinal tract
      in urological profile patients. MATERIALS AND METHODS: Retrospective analyses of
      1960 esophagogastroduodenoscopy were performed in the Clinical Urological
      Hospital No 47 for the period 2004-2010. THE RESULTS: Ezogofago
      gastroduodenoscopy in CUH No 47 is performed at an average 3.8% of patients, the
      acute erosive and ulcerative lesions of the gastrointestinal tract are detected
      at an average of 50.7% of patients; most often acute erosive and ulcerative
      lesions of the upper gastrointestinal tract occur in the prostate adenoma,
      prostate tumors, kidney, bladder, as well as nephrolithiasis, complicated by
      active pyelonephritis; 94.4% of total accounts of all identified exacerbations
      are peptic ulcer and stress ulcer; the greatest risk of ulcer complications
      accompanied by cystectomy, prostatectomy, nefroektomy performed for oncologic
      indications (respectively 59.6%, 53.7%, 18.2%). CONCLUSION: The urological
      oncology organ removing interventions are accompanied by a high probability of
      postoperative complications of ulcers, and the mere presence of malignancy
      appears as specific, significant risk factor.

PMID- 22629741
TI  - [Esophagus lesions after surgical resection].
AB  - The article is a an overview of the literature data on pathogenetic aspects of
      the development of reflux esophagitis, metaplasia, dysplasia, cancer of the
      esophagus after gastrectomy and partial gastrectomy in the experiment and
      clinical practice.

PMID- 22629742
TI  - [Various mechanisms of heart failure in liver diseases].
AB  - The article is a review of the literature on the problem of heart disease in
      liver cirrhosis of different etiologies (alcohol, amyloidosis, hemochromatosis,
      viral lesions of the heart). Examined in detail the pathogenesis of cirrhotic
      cardiomyopathy and diagnosis, occurring in cirrhosis of any etiology. This
      article presents a noninvasive methods of diagnosis of myocardial fibrosis using
      serum markers of fibrosis, myocardial fibrosis degree of calculation on the basis
      of echocardiography and ECG.

PMID- 22629743
TI  - [International Consensus for the treatment of patients with upper
      gastrointestinal bleeding. A critical analysis].
AB  - Paper is devoted to the discussion made at a workshop of international experts
      agreed recommendations (Consensus) for the treatment of bleeding of the upper
      gastrointestinal tract. In order to accommodate new data and determine the
      tactics of patients with gastrointestinal bleeding (International Consensus Upper
      Gastrointestinal Bleeding Conference Group). We present some of the agreements
      with some comments. Offers a wide discussion of these recommendations to make
      them as a guide in Russia.

PMID- 22629744
TI  - [Diagnostic criterion for anorexia nervosa].
AB  - Article presents a case of anorexia in 29 years old patient. Described the
      clinical symptoms of anorexia, the manifestations of the disease in patient; the
      premorbid characteristics of personality, the formation of which influences on
      relationships with parents.

PMID- 22629745
TI  - [The choice of primary surgery for perforated chronic duodenal ulcer].

PMID- 22629746
TI  - [Report of the 19th European Gastroenterology Week (October 22-26, 2011,
      Stockholm, Sweden)].

PMID- 22629747
TI  - [Report of the IV National Congress of Therapists (November 23-25, 2011,
      Moscow)].

PMID- 22629748
TI  - [Eradication efficiency and Helicobacter pylori resistance to antibiotics in
      anticipation of IV TH Maastricht consensus issues publication. Editorial].

PMID- 22629750
TI  - [Duodenogastral reflux burden gastroesophageal reflux disease].
AB  - The article presents research data of duodenogastral reflux (DGR) role in
      patients with gastroesophageal reflux disease. It is shown that in the presence
      DGR, the reflux esophagitis is detected at a higher frequency and outside of
      esophageal manifestations of the disease. The comorbidities of hepatobiliary zone
      and pancreas contributes to the DGR development, as well as the syndrome of
      bacterial overgrowth in the small intestine.

PMID- 22629749
TI  - [Optimal diagnostic criteria of ENT manifestations of GERD].
AB  - BACKGROUND: GERD has a number of extraesophageal manifestations (EEM) such as
      ENT, pulmonary etc. 24-hours pH monitoring in distal esophagus is widely used to
      confirm the diagnosis but its cut-off values for the diagnosing of
      extraesophageal manifestations of GERD (for example ENT) are unknown. AIM: To
      evaluate the optimal cut-off values for mean pH, time pH < 4 a day in the
      proximal esophagus and number of high gastroesophageal refluxes (HGR) in regard
      to presence of extraesophageal manifestations of GERD. METHODS: Ninety one GERD
      patients (50 men, 41 women, 42.33 +/- 16.1 y.o.) were examined using dual-probe
      24-hours pH monitoring. The proximal probe was placed in the upper 1/3 part of
      esophagus over the upper esophageal sphincter. To confirm the presence of ENT
      manifestations of GERD all the patients were examined by qualified ENT
      specialist; special ENT tests (laryngoscopy, pharyngoscopy with cytology and
      bacteriology) were performed. Toxic, allergic and infectious etiology of ENT were
      exclusion criteria. ROC curve analysis was used to evaluate optimal cut-off
      values of pH-studies. The cut-off values were chosen by the optimal diagnostic
      sensitivity (DSp)/specificity (DSp) ratio. RESULTS: ENT diseases were found in 59
      of all the examined patients (chronic pharyngitis in 79.66% of them). HGR was
      found in 76.27% of patients in ENT group and in 43.75% of controls (consisted of
      GERD patients without signs of ENT pathology, n = 32), p = 0.0026. Mean number of
      HGRs was higher in ENT group compared to controls: (M +/- s) 12.51 +/- 18.56 vs
      2.84 +/- 7.11 respectively, p (Mann-Whitney U-test) = 0.0003. Mean pH levels in
      the proximal esophagus were lower in the ENT group: (M +/- m) 6.32 +/- 0.52 vs
      6.58 +/- 0.42, p = 0.011. Mean time pH <4 in the proximal esophagus differed
      significantly between ENT and GERD patients without ENT: 3.19 +/- 6.76 min in ENT
      group compared to 2.42 +/- 10.02 min in controls, p = 0.003. The calculated cut
      off values for the number of high GER were 2 (DSn 71.19%, DSp 68.75%) or 3 (DSn =
      61.02%, DSp = 71.88%); for mean pH in the proximal esophagus--6.3 (DSn = 75%, DSp
      = 51.47) or 6.4 (DSn = 68.75%, DSp = 58.82%); for time pH < 4--optimal value was
      25 sec (DSn = 72.88%, DSp = 68.75%). CONCLUSIONS: Proximal pH monitoring may be
      useful in diagnosing extraesophageal manifestation of GERD. Optimal cut-off
      values of number of high GER are 2 to 3, mean pH 6.3-6.4 and time pH < 4 - 25
      sec.

PMID- 22629751
TI  - [Endoscopic negative GERD: psychogenic nature of somatic complaints].
AB  - The aim is to study the characteristics of the operation of psychological
      defenses in patients with endoscopically negative gastroesophageal reflux
      disease. On the example of a survey of 60 patients showed that the actual mental
      status of patients, being an inpatient at the endoscopically negative GERD,
      characterized by a high degree of neuroticism in comparison with GERD patients
      under reflux esophagitis. This fact is considered in terms of imperfect mental
      protection, among which the most common in these patients is the suppression of
      the negative emotional experiences. As one of the possible causes of resistance
      to therapy is considered the psychological phenomenon of "secondary gain from
      illness".

PMID- 22629752
TI  - [Prevalence of ulcer disease complications].
AB  - The epidemiology of complications of a peptic ulcer is studied: bleedings,
      perforations and pylorodudenal stenoses. 1799 patients are included in research
      that were on hospitalisation in 1995-2009. A frequency of all the complications
      has declined. Middle age of patients with the complicated ulcer enlarged: in case
      of an ulcerative bleeding--at the expense of reduction of a share of male at the
      age of 36-60 years, in case of a perforated ulcer--because of appreciable
      reduction of a percentage of male at the age of 21-35 years.

PMID- 22629753
TI  - [Adherence to treatment patients with the digestive system chronic diseases].
AB  - The purpose of study is to expand notions of personal factors of adherence to
      treatment chronic diseases of digestive system. The article presents data on the
      patients accuracy of performing medical recommendations on pre-hospital and in
      the delayed period. Analyzed the influence of socio-demographic characteristics
      (gender, age, educational level), the characteristics of the disease (duration of
      history, the frequency of hospitalizations, complications) to the compliance of
      patients. The psychological aspect of the formation of adherence to treatment was
      considered in the interactions of personality and disease. Was underlined the
      role of the doctor's deontological work aimed on the involving of the personality
      of patient in therapeutic process as an active subject of the therapeutic
      interaction.

PMID- 22629754
TI  - [Reflection of state of hunger and its changes under the influence of meals in
      time structure of myoelectrical activity of esophageal-gastric sphincter and
      gastric in rabbits].
AB  - OBJECTIVE: To study the reflection of the state of hunger and its changes under
      the influence of food intake in temporal structure of myoelectrical activity of
      gastro-esophageal sphincter and stomach in rabbits. MATERIAL AND METHODS: The
      registration of myoelectrical activity of gastro-esophageal sphincter and the
      stomach was performed in 10 rabbits subjected to daily food deprivation, before
      and after providing them powers ac DA-100 C and EMG-100 C (USA). Automatic
      analysis of temporal parameters of myoelectrical activity was monitored by the
      program AcqKnowledge (USA). Statistical analysis of the temporal parameters was
      performed using the program Statistica 6. RESULTS: The condition of hunger is
      characterized by irregular periods of slow waves generated by the muscles of
      gastro-esophageal sphincter, the body and antrum, which is reflected in the
      structure of their temporal organization in the form of bimodal distribution of
      periods of slow waves. Under the conditions of food deprivation regular
      generation of slow waves with a frequency of 3.6 cycles/ min is observed only in
      the lesser curvature--stomach pacemaker zone, as evidenced by the monomodal
      character distribution of periods of slow waves. However, the ability of muscles
      of the lesser curvature to define the maximum frequency of generation of slow
      waves to other parts of the stomach under the conditions of hunger is not fully
      realized. Food intake reinforcement reduces the inhibitory effect of hunger
      motivational excitation on the activities of myogenic pacemaker of the stomach,
      allowing the muscles of the lesser curvature to define a maximal rhythm of
      generation of slow waves to the muscles of the body and antrum, as evidenced by
      the monomodal distribution of periods of slow waves. In a state of satiation the
      maximum frequency of generation of slow waves of myogenic pacemaker of the lesser
      curvature is acquired by muscles of gastro-esophageal sphincter. CONCLUSION: The
      state of hunger and its change under the influence of food intake finds
      reflection in the specific structure of the temporal organization of the slow
      electrical activity of muscles of gastroesophageal sphincter and the stomach.

PMID- 22629755
TI  - [Caused by ethanol gastric mucosa damage in mice before and after pulse
      repetitive microwave exposure].

PMID- 22629756
TI  - [Primary prevention of reflux esophagitis in achalasia of cardia].
AB  - Aim of the study was to compare the incidence of reflux esophagitis in patients
      with achalasia cardia after successful surgical treatment with balloon dilatation
      and ezofago-cardio-seromyotomy followed by fundoplication according toToupet
      type. The study included only those patients with eliminated symptoms of
      dysphagia. All patients were divided into two groups depending on the method of
      treatment. In the first group (20 patients) performed balloon dilatation, second
      group (20 patients)--laparoscopic ezofagocardioseromiotomiya followed by
      fundoplication according type Toupet. Results evaluated one year after the
      intervention. Revealed that the incidence of reflux esophagitis were
      significantly higher in group of patients after balloon dilatation, than in the
      group of operated patients--40 and 15% respectively (p < 0,05). Received results
      allow to reconsider approaches to the selection of treatment method of achalasia
      cardia in favor of laparoscopic ezofagocardioseromitomii with the formation of
      posterior cuff-type Toupet.

PMID- 22629757
TI  - [Diagnostic and treatment of gastroesophageal reflux disease].
AB  - We propose a diagnostic algorithm based on the evaluation of GERD symptoms, the
      test results with a single dose of alginate with heartburn and EGD-
      esophagogastroduodenoscopy data. The diagnosis of GERD with reflux esophagitis
      based on the endoscopic detection of characteristic changes of esophagus.
      Diagnostic criteria endoscopically negative forms of GERD are the presence of
      symptoms of concern to the patient, the absence of damage to the esophagus during
      EGD and rapid relief of heartburn, a single dose of alginate (alginate positive
      test). Drug of choice for reflux esophagitis is an PPI. Specify the role of
      Helicobacter pylori diagnosis, indications for eradication in patients with GERD.

PMID- 22629758
TI  - [State of the colon after cholecystectomy].
AB  - Study of the colon was carried out in patients with cholelithiasis after
      cholecystectomy. Estimated clinical symptoms, the mucous membrane status by the
      results of the histological, morphometric methods, computed ploidometry and
      immunomorphology of colon biopsy specimens. Mucosal atrophy, the buildup of
      sclerotic processes and proliferative activity of colonocytes was significantly
      more frequent in patients with cholecystectomy in history, than in patients with
      cholelithiasis and the control group. Most of the examined patients have
      disorders of the colon microbiocenosis. Use of domestic liquid synbiotic
      complexes Normoflorin L and B allowed to hold a successful correction of
      disbiosis.

PMID- 22629759
TI  - [Helicobacter pylori as a part of microbiocenosis of mucosal microflora esophago
      gastroduodenal zone in the norm and pathology].
AB  - AIM; Revealing the level and significance of Helicobacter pylori (H. pylori) in
      the normobiocenosis and disbacteriosis of mucosal microflora in the
      osophagogastroduodenal zone. MATERIAL AND METHODS: Qualitative and quantitative
      composition of the mucosal microflora was defined in biopsy specimens from
      different parts of oesophagus, stomach and duodenum in addition to clinical and
      histological examination in 50 healthy volunteers, 106 ulcer duodenum patients,
      24 patients with gastric ulcer, 36 with chronic gastritis and 24 with chronic
      oesophagitis. RESULTS: H. pyloril is involved into normomicrobiocenosis of the
      mocosal microbiota and take part of main defensive function of gastroduodenal
      tract. Excerbation of peptic ulcer, chronic gastritis and oesophagitis is
      accompanied with the reduction H. pylori in most cases, though the scar formation
      occurs both with and without presence of H. pylori. CONCLUSION: The colonization
      of the oesophagogastroduodenal zone by H. pylori has no infection process and
      play the independent role in the development of the ulcer disease, gastritis and
      oesophagitis and does not require the eradication.

PMID- 22629760
TI  - [Selection of "surrogate" and "endpoints" evaluation of the efficacy of medical
      interventions].
AB  - With the advent of new medical technologies and medicines, as well as due to
      changes in disease patterns and demographic problems rises the need for continued
      increases in health spending. Increased costs can be totally inadequate, if it
      has been done without studying the effectiveness of medical interventions, based
      on the results of evidence-based medicine and economic of their feasibility. To
      evaluate the clinical effectiveness of medical interventions have been recently
      used specific criteria, so called points of clinical efficacy (surrogate and
      endpoints), that allow to conclude feasibility or harmfulness of the introduction
      or application of the intervention in clinical practice. The endpoint is reliable
      indicator the effectiveness of medical intervention. Surrogate point--is a
      biomarker that is intended to replace the endpoint and is a predictor of the
      effectiveness of medical intervention. The use of surrogate points has several
      advantages such as simple in identification and measurement, as well as more
      higher in compare with endpoints the vents frequency, that can significantly
      reduce the size of the selection and duration and cost of clinical trials,
      respectively. Finally, the surrogate points allow to evaluate treatment effect in
      situations where the use of endpoints is difficult or is unethical.

PMID- 22629761
TI  - ["Internal runny nose," and gastroesophageal reflux disease: diagnosis, treatment
      of patients].
AB  - The article observes the main up to date questions of pathogenesis, diagnostics
      and treatment of patients with GERD and postnasal drip syndrome.

PMID- 22629762
TI  - [Bone metaplasia in the gallbladder wall].

PMID- 22629763
TI  - [2nd prize in the competition of works in hepatology GSSR 2010 new approaches to
      treatment of patients with Nash type 2 diabetes].

PMID- 22629764
TI  - [2nd prize in the competition of scientific works of young scientists in
      gastroenterology GSSR 2010].

PMID- 22629765
TI  - [2nd prize in the competition of young scientists in the XVIII National Congress
      "Man and Medicine" of 2011].

PMID- 22629767
TI  - [Report on Celiac Disease International Symposium (Oslo, Norway, June 20-23,
      2011)].

PMID- 22629766
TI  - [The outstanding Russian clinician V.D. Shervinsky and his ideas about the fight
      against alcoholism (to the 70th anniversary on his death)].

PMID- 22629768
TI  - [Oncogenesis humoral mechanisms regulation and NSAIDs ability in prevention of
      tumors].
AB  - The article observes modern data in mechanisms and pathways of carcinogenesis and
      tumor progression and the role of oncogenes, cytokines, growth factors in this
      process. The protective effects of aspirin and nonsteroidal anti-inflammatory
      drugs (NSAIDs) for colorectal cancers in experimental and clinical studies are
      also demonstrated in this review.

PMID- 22629769
TI  - [The immune status changes in patients with inflammatory bowel disease under the
      influence of mesenchymal stromal cells and infliximab therapy].
AB  - Out of 28 patients with inflammatory bowel disease in 11 (39.3%) revealed the
      presence of autoantibodies to gastric parietal cells. Appointment of MSC and
      infliximab did not lead to a reduction in antibody levels, in fact, in 6 (21.4%)
      patients had a further increase in the content of mentioned autoantibodies.
      Identification of autoantibodies to gastric parietal cells is considered as
      adherence to IBD autoimmune gastritis (formation of a systemic process) that
      requires use of corticosteroids. Transplantation of mesenchymal stromal cells in
      IBD reduces enhanced circulation of autoantibodies against antigens of
      neutrophils cytoplasmic structures, thereby reducing the severity of autoimmune
      reactions. Transplantation of MSCs reduces autoaggression in patients with
      ulcerative colitis, reducing the autoreactive clone of B lymphocytes (CD19+CD5+).
      Analysis effectiveness of the therapy. Transplantation of MSCs in IBD has a
      systemic immunoregulatory effect: on the one hand, stimulates oppressed cytokine
      synthesis, on the other--reduses the intensity of the autoimmune reactions and
      activity of pathological processes. Infliximab selectively blocks TNF-alpha,
      without affecting other proinflammatory cytokines.

PMID- 22629770
TI  - [Quality of life in inflammatory bowel disease patients].
AB  - OBJECTIVE: To study the quality of life (QOL) patients with inflammatory diseases
      (IBD), gender and age characteristics of QOL, as well as its dynamics under the
      influence of biological and standard therapy. MATERIAL AND METHODS: Investigation
      of QOL using the SF-36 was performed on 90 patients with IBD, among them 35 with
      Crohn's disease, 55--ulcerative colitis. Mean age 35.2 +/- 1.2 years, men--53,
      women--37. Severity of symptoms of IBD (by Best and Truelove): mild--7 (7.7%),
      moderate--69 (76.6%), severe--14 (15.7%), extraintestinal manifestations were
      present in 34 (37.8%) patients. After a year was conducted the survey in 31
      patients (group 1) after standard therapy with 5-aminosalicylic acid (5-ASA),
      corticosteroids (GCS), 29 patients (Group 2)--after systemic transplantation of
      mesenchymal stromal cells (MSCs) of 27 patients (group 3)--Treatment with
      infliximab (IFX). The results. QOL was reduced in all patients in all scales of
      the questionnaire, including adverse changes in the psycho-emotional and social
      spheres. In the dynamics under the influence of the therapy, especially in
      achieving complete clinical and endoscopic remission, tendency to improve the
      performance of most QOL was more pronounced in patients with IBD treated with
      biological therapy MSCs and inflation, compared with patients receiving standard
      therapy. Identified gender differences in indicators of QOL that requires to
      develop psychosocial rehabilitation programs that take into account these
      differences. It is concluded that the need for participation of psychologists and
      neuropsychiatrists gastroenterologist in joint management and treatment of IBD.
      Was concluded the necessity of psychologists and neuropsychiatrists and
      gastroenterologist participation in joint management and treatment of IBD.

PMID- 22629771
TI  - [Clinical and functional characteristics of small intestine in the metabolic
      syndrome].
AB  - THE AIM: Complex investigation of the small intestine functional condition in
      metabolic syndrome. MATERIALS AND METHODS: The 65 patients with metabolic
      syndrome were examined. We used clinical data and complex examination of the
      small intestine function by tests with mono-, di- and polycarboanhydrates.
      RESULTS: In mojoriti of patients (82.9%) the clinical local and common signs of
      small intestine lesion were reviled. In study intestine function the disturbances
      in all stages of hydrolysis and resorbtion were found. CONCLUSION: Exchangings of
      the small intestine functional condition in metabolic syndrome are not only
      secondary, but lead to its progressing.

PMID- 22629772
TI  - [Morphological features and esophago-gastroduodenal zone microbiocenose in
      patients with syndrome postcholecystectomic syndrome].
AB  - Endoscopical and histological features of oesophagogastroduodenal zone,
      parameters of pH-metry and electrogastroenterography, qualitative and
      quantitative characteristics of microbiocenosis were studied in 80 female persons
      with postcholecystectomy syndrome more then a year after cholecystectomy. In the
      presence of duodenogastral reflux the most natural is the combination of distal
      oesophagitis, antral atrophic gastritis and duodenitis, accompanied with low
      level of gastric acidity, gastric hypokinesis and duodenal dyskinesis,
      dysbacteriosis of mucosal microflora with its quantitative increase and
      appearance of bacteria with expressed pathogenicity non-typical for this biotope.
      These data should be taken into consideration for determination of pre- and
      postoperative treatment tactics for patients with gallstones.

PMID- 22629773
TI  - [Intensity of free radical oxidation and superoxide dismutase activity in
      patients with drug hepatitis in combination therapy with melaxen or epifamin].
AB  - Intensity of free radical oxidation processes and superoxide dismutase activity
      at patients with drug-induced hepatitis at the combined therapy with melaxen or
      epifamin. Free radical homoeostasis state at patients with drug-induced hepatitis
      being on standard treatment, including hepatoprotectors, and the combined therapy
      with melaxen or epifamin has been investigated. Biochemiluminescence parameters
      in blood serum point out to intensification of free radical processes and
      inhibition of antioxidant defense of organism, at this time superoxide dismutase
      activity in blood serum increased. After leading of standard therapy a decline of
      oxidative stress expression was observed. Incorporation to base treatment of
      melaxen or epifamin accompanied by correction of antioxidant status of organism
      and provided more expressed antioxidant effect, that confirmed by changing of
      biochemiluminescence parameters and superoxide dismutase activity. Obviously, it
      is related to antiradical properties of melatonin the level of which is corrected
      under the action of these preparations.

PMID- 22629774
TI  - [Abnormal liver function during therapy with amiodarone in patients with
      persistent atrial fibrillation].
AB  - The aim of this work was to analyze the prevalence of level function disorder in
      patients with atrial fibrillation taking constantly amiodarone. Two groups of
      patients were studied: in group 1 (n = 78) patients with persistent atrial
      fibrillation taking constantly amiodarone for rhythm control were included, group
      2 (n = 67) consisted of patients with permanent atrial fibrillation taking
      propafenon, ethacizine and digoxin for rate control. In studied groups liver
      transaminase activity and data of liver echography after 90 +/- 8 days of
      treatment were estimated. In 51.58% patients of group 1 asymptomatic increase of
      liver transaminase activity was found. If liver transaminase activity had been
      raised before taking amiodarone, frequency and degree of liver transaminase
      increase extended. Consequently, patients taking constantly amiodarone, require
      dynamic control of GGTP, AIAT, AsAT once a quarter. If liver transaminase
      activity increases because of amiodarone taking the method of treatment is
      possible to be changed and rate control therapy may be chosen.

PMID- 22629775
TI  - [Therapeutic possibilities hepatoprotectors in alcoholic liver cirrhosis].
AB  - The aim of the study was to investigate the therapeutic opportunities of S
      adenosylmethionine and polyunsaturated lecithin in Child class A patients with
      alcoholic liver cirrhosis using transient elastography. MATERIALS: The 38 males
      Child class A alcoholic liver cirrhosis were investigated. RESULTS: The use of S
      adenosylmethionine or polyunsaturated lecithin in patients with alcoholic liver
      cirrhosis is reasonable cause of their possibility to reduce the fibrogenesis in
      liver tissue and of their possibility to improve the function of remained intact
      hepatocytes. Thus use of this remedies prevents progression of cirrhotic
      transformation of the liver and gives a patient an opportunity to get the stable
      clinical status.

PMID- 22629776
TI  - [Treatment of tobacco dependence in patients with chronic diseases of digestive
      system].
AB  - The purpose of this study was to increase the effectiveness of tobacco control by
      improving the treatment of tobacco dependence. The article presents the data
      results of different methods of treatments of tobacco dependence among 135
      patients with digestive diseases. As the most effective is a comprehensive
      approach combining psychotherapy and physiotherapy methods is designated. The
      possible reasons of due treatment effect absence are separately analysed: a sharp
      severity of tobacco withdrawal syndrome, inadequate primary motivation of smoking
      refusal, premorbid personality characteristics, a pathological variant of
      response to disease.

PMID- 22629777
TI  - [Morphofunctional characteristics of the colon in mice Balb/c in remote terms
      after splenectomy].
AB  - BACKGROUND AND AIMS: Hypersusceptibility to pathogens, including enterobacteria
      is the most serious late result of splenectomy. The aim of these studies was to
      give the morphofunctional characteristics of large bowel and to analyze luminal
      bacterial ecosystem disturbances as late results of splenectomy. METHODS: Fourty
      male mice Balb/c with body mass 18-20 g were divided in random manner: control
      group consisted of ten intact mice, 15 mice in each of two experimental groups
      subjected to splenectomy. All animal were carried in standard housing conditions
      and feeding and were upset of the experiment on the 30th (experimental group I)
      and 60th (experimental group II) days after the splenectomy. For the histological
      investigation the pieces of colon were taken and processed in standard
      histological methods. The blood out of cardial cavity was sampled for estimation
      of the endotoxin level; faeces for the analyzing of luminal bacterial ecosystem
      disturbances (dysbios) were taken out of the rectum. RESULTS: At the 30th day
      after splenectomy the pattern of chronic catarrhal colitis was at the
      histological the stroma by lymphocytes and neutrophils. At the 60th day at the
      histological slides the increasing of mitotic activity of epithelial cells in
      crypts of the colon and activation of the inflammative infiltration were
      observed. The endotoxin level half as large again in comparison with the control
      one at the 30th day. The I-II stages of dysbiotic disturbances were recognizes by
      bacterial methods at the 30th day with the following development up the II stage
      at the 60th day. CONCLUSIONS: The chronic catarrhal colitis with accompanying
      disturbance of luminal bacterial ecosystem (dysbiotic state of Stages I-II) and
      increasing og the endotoxin level in the blood are among other late results of
      splenectomy in mice Balb/c model

PMID- 22629778
TI  - [Effect of electrostimulation "hunger center" of lateral hypothalamus on the
      impulse activity of masticatory muscles in unfed and fed rabbits in the absence
      and the presence of food].
AB  - In chronic experiences on rabbits the influence of electrostimulation of "the
      hunger centres" of the lateral hypothalamus (LH) on impulse activity of chewing
      muscles of rabbits under the conditions of hunger and satiation was studied. It
      is established, threshold irritation of the LH of hungry and preliminary fed
      animals in the absence of food caused the occurrence of incessant search behavior
      which was followed by the regular generation of bursts of AP by masseter and
      mylohyoideus muscles with bimodal distributions of interpulse intervals. Such
      reaction of chewing muscles during irritation of the LH in the absence of food is
      an example of advancing type reaction. The increase of level of alimentary
      motivation, arising at threshold irritation of the LH of rabbits under the
      conditions of hunger and satiety during the resultant food-intake behavior,
      increased frequency of generation of bursts of AP in a phase of the capture of
      food, but did not influence on this indicator in a phase of chewing of food. The
      received results testify about descending stimulating influences of alimentary
      motivational excitation on neurons of the chewing centre in medulla and on
      impulse activity of chewing muscles.

PMID- 22629779
TI  - [Diagnosis and surgical treatment of gallbladder cancer].
AB  - Retrospective analysis of 72 patients with diseases of gall bladder cancer was
      conducted. The difficulty of differential diagnosis of tumors of the biliary
      tract, the rapid progression of tumors and a high postoperative mortality (19.6%)
      were noted. Presented recommendations for early detection of disease and improve
      treatment outcomes.

PMID- 22629780
TI  - [Modern aspects of surgical treatment of combined gallstone disease and
      multifocal atherosclerosis aorta and its branches].
AB  - Lipidic metabolism infringements in the organism according with pathology of
      hepatocyts generates plural associated diseases. On prevalence and weight of
      metabolic damages the first place occupy cholelithiasis and atherosclerosis.
      Results of treatment of 752 patients with an atherosclerosis and cholelithiasis
      after surgical intervention was analysed. Basing on studying pathophysiological
      shifts at simultaneous cholelithiasis and atherosclerosis the algorithm of
      examination and tactics of the surgical treatment (simultaneouse or stage
      operations) are optimised, criteria for application of miniaccesses operations
      are specified.

PMID- 22629781
TI  - [Features of bone metabolism in patients with chronic diseases of digestive
      system].
AB  - Paper is devoted to the study of the clinical features of the course diseases of
      gastrointestinal tract and liver in the formation of osteopenia and osteoporosis.
      Given frequencies of occurrence of infringements of mineral density of bone at
      patients with chronic pancreatitis, cirrhosis, cholelithiasis, inflammatory bowel
      disease as well as diseases that are accompanied by malabsorption syndromes
      (celiac enteropathy syndrome of short small intestine). Established populational
      (age, sex, lower body mass index, menopause), clinical and laboratory factors
      indicating high risk of lower bone mineral density in these patients.

PMID- 22629782
TI  - [Health problems and diseases, diagnosis and treatment of the historical and
      philosophical positions].

PMID- 22629783
TI  - [Nifuratel application in treating patients with Giardia, combined with
      intestinal dysbiosis].

PMID- 22629784
TI  - [Comparative assessment of survival of probiotic microorganisms from commercial
      preparations under the conditions in vitro].
AB  - PURPOSE OF THE STUDY: Assessment of survival of probiotic microorganisms from
      commercial preparations under the conditions in vitro simulates digestion in
      human stomach and intestine. MATERIALS AND METHODS: Probiotic microorganisms from
      domestic and foreign commercial preparations were used in experiments. Study of
      survival of probiotic microorganisms was carried out on the model in vitro
      simulates the conditions of digestion in the human body. RESULTS: A significant
      reduction in the number of viable probiotic microorganisms in the 20 of 23
      studied commercial preparations during their incubation in the model media is
      established. Probiotic microorganisms in the preparations Bactisubtil,
      Sporobacterin and Biosporin possess a good survival under the conditions in
      vitro. CONCLUSION: The selection of probiotics for the correction of intestinal
      microbiocenosis requires an individual approach that takes into account the
      character of relations of probiotic microorganisms and indigenous microorganisms
      of patient as well as the possibility of using advanced prebiotics in the combine
      treatment of dysbacteriosis.

PMID- 22629785
TI  - [Experimental study of sensitivity of probiotic microorganisms to antibacterial
      drugs].
AB  - PURPOSE OF THE STUDY: Investigation of sensitivity of probiotic microorganisms to
      antibacterial drugs. MATERIALS AND METHODS: Probiotic microorganisms from
      domestic and foreign commercial preparations were used in experiments. The study
      of sensitivity of probiotic microorganisms to antibacterial drugs was carried out
      using solid nutrient medium containing calculated amount of antibacterial drugs.
      RESULTS: Probiotic microorganisms are mainly sensitive to the representatives of
      the major classes of antibacterial drugs. Only some of the studied microorganisms
      are resistant to 1-4 antibiotics. CONCLUSION: When choosing a probiotic in the
      treatment of dysbacteriosis need to consider whether th antibiotic therapy was
      carried out. The use of antimicrobial drugs, even in therapeutic doses, reduces
      the viability of probiotic microorganisms and their survival in the gut.

PMID- 22629786
TI  - [The substantiation of UDCA usage in functional disorders of biliary tract].
AB  - Ursodeoxycholic acid (UDCA) has been widely used in clinical practice, more
      frequently in liver diseases treatment. Studies have shown that UDCA has
      choleretic and cholecyst-kinetic effects. In this paper we give pathogenetic
      substantiation of UDCA use in the gall bladder dysfunction, hypotension, and
      identified in clinical usage of UDCA in hypokinesia of the gallbladder.

PMID- 22629787
TI  - [The cost effectiveness of adalimumab in Crohn's disease (review of foreign
      pharmacoeconomic studies)].

PMID- 22629788
TI  - [NSAID-induced damages esophagus. Farmakoprotective opportunities].

PMID- 22629789
TI  - [UDCA in the treatment of nonalcoholic fatty liver disease].
AB  - As a signaling molecule with system endocrine function, UDCA improves insulin
      sensitivity by activating the nuclear farnezoid X-receptor; as a ligand for the
      TGR5/Gpbar-1 receptor, UDCA is able to stimulate the secretion of GLP-1. UDCA
      ameliorate of the anti-oxidative defenses in NAFLD, normalizes NAD+/NADH ratio,
      beta-oxidation. UDCA improves the liver biochemical and histological picture in
      NASH, also reduces hepatocytes apoptosis and restores adiponectin levels; in
      other studies, these data are not confirmed. In the experiment, UDCA prevents the
      development of steatosis in the liver. UDCA may increase efficiency in
      combination with statins, thiazolidinediones, vitamin E. Further controlled
      prospective trials are needed for research of the UDCA effect in NAFLD.

PMID- 22629790
TI  - [Experience of preservation remission in inflammatory bowel diseases].
AB  - The results of hyperbaric oxygenation and correction (HOC) method of intestinal
      microflora by liquid sinbiotic biocomplex "Normoflorin" at the second phase of
      the treatment of IBD under conservation of remission. The unresolved issues of
      minimization of adverse events and improvement the quality of life of patients
      with IBD, reveal the actuality of the problem. The results of joint usage of the
      method of hyperbaric oxygenation and correction method with liquid intestinal
      microflora synbiotic biocomplex "Normofloriny", allow a better correction
      mikrobiocenozis of the bowel. Biocomplexes "Normofloriny" and the HBO method
      should include treatment programs for patients with IBD during the maintenance of
      remission.

PMID- 22629791
TI  - [Fulminant form of ulcerative colitis].
AB  - The article contains short literature review of fulminant ulcerative colitis.
      Clinical case is presented too. Difficulties of which were large severe
      destruction of colon at the beginning of the disease; progressive intestine
      bleeding threatening the life of the patient.

PMID- 22629792
TI  - [3rd place in the competition of scientific work in hepatology in 2010. Treatment
      of patients with overlap of primary biliary cirrhosis and autoimmune hepatitis].
AB  - This paper analyzes the results of different treatments overlap (OS) of primary
      biliary cirrhosis (PBC) and autoimmune hepatitis (AIH): ursodeoxycholic acid
      monotherapy (UDCA) monotherapy with prednisolone (PD), the combination of PD with
      UDCA. Results of treatment of 16 OS patients with glucocorticoid last generation-
      budesonide (BS) in combination with UDCA. The treatment results were estimated in
      reducing severity of intrahepatic cholestasis (IHC), proposed by the author, as
      well as the degree of reduction of the biochemical activity of enzymes. Evaluated
      the quality of life by SF-36 questionnaire. In addition, the efficacy of
      budesonide in combination with UDCA was assessed by morphological examination of
      liver tissue in the dynamics after 6 months of treatment. The paper convincingly
      demonstrate that combination therapy OS is more effective in monotherapy reducing
      clinical and biochemical disease activity, as well as positive effects on quality
      of life. The advantages of the use of budesonide in combination with UDCA prior
      systemic glucocorticoids: a high efficiency and low risk of side effects.

PMID- 22629793
TI  - [3rd place in the competition of scientific works of young scientists in
      gastroenterology in 2010. Clinical and pathogenetic mechanisms of formation of
      food intolerance in children].

PMID- 22629794
TI  - [Nikolai Burdenko Nilovich. For 135th anniversary of the birth].

PMID- 22629795
TI  - [Acute diarrhea].

PMID- 22629796
TI  - [Algorithm of differential and topical diagnosis of obturation jaundice and
      miniinvasive correction of the main bile diverting pathways passability].
AB  - The results of examination and treatment of 746 patients, suffering obturation
      jaundice of various origin, were analyzed. A diagnosis-treatment algorithm for
      obturation jaundice was elaborated. Two-staged treatment was conducted in the
      patients: endoscopic decompression of a bile diverting pathways for normalization
      of the hepatobiliary system organs function and operative intervention, using
      miniinvasive technologies. Introduction of the surgical tactics elaborated for a
      staged and rational conduction of a bile restoration operations with application
      of miniinvasive technologies have permitted to lower significantly the
      postoperative complications rate down to 7.5% and postoperative lethality--to
      0.8%.

PMID- 22629797
TI  - [Application of antihelicobacter therapy in patients, suffering pyloroduodenal
      zone ulcers, complicated by hemorrhage].
AB  - There were examined 113 patients, suffering pyloroduodenal zone ulcers,
      complicated by an acute hemorrhage. H. pylori was revealed in 108 (96%) patients.
      To escape a false-negative results a serological method was applied, which was
      used to determine a content of IgG antibodies to H. pylori with the help of
      diagnostic panel GastroPanel (Biohit PLc firm, Finland). The H. pylori presence
      in patients must be considered as a risk factor for the early recurrent
      hemorrhage occurrence. A timely conducted examination, determination of H. pylori
      and timely prescription of antihelicobacter therapy promote the improvement of
      the treatment results in patients, suffering gastroduodenal ulcers, complicated
      by an acute hemorrhage due to reduction of the occurrence rate of early
      recurrence of hemorrhage.

PMID- 22629798
TI  - [Dynamics of the main immunological indices in patients, suffering gastroduodenal
      ulcers, complicated by hemorrhage].
AB  - A deep clinical, immunological, microbiological analysis was performed in
      patients, suffering gastroduodenal ulcer, complicated by hemorrhage.
      Immunodeficiency state with the signs of autoimmunization was noted in the
      patients. These changes were most severe in a severe blood loss, the local
      endoscopic hemostasis instability, high risk of the hemorrhage recurrence
      occurrence, presence in a periulcer zone mucosa of a conditionally pathogenic and
      pathogenic microflora with a Klebsiella pneumoniae and Streptococcus beta
      haemoliticus predominance. The analysis of the data obtained permits to
      prognosticate the pathologic process severity course and to improve the program
      of treatment.

PMID- 22629799
TI  - [Correction of the immunity disorders in patients while surgical treatment of
      coexistant gastroduodenal ulcers].
AB  - There were examined 64 patients, suffering combined gastroduodenal ulcers.
      Subpopulations of lymphocytes, using monoclonal antibodies, were used to estimate
      the patients immune status. The investigation was performed in a dynamics:
      immediately after admittance to hospital, on the operation day and on the tenth
      postoperative day. In 33 patients (the main group) reamberin was applied in a
      complex of surgical treatment and in 31 (the comparison group)--the conventional
      medicinal preparations. In all the patients before the treatment conduction there
      were revealed the cell immunity chain disorders like in a secondary immune
      deficiency state (SIDS). The SIDS elimination and the immunological indices
      improvement were promoted by incorporation of reamberin in the complex of
      surgical treatment.

PMID- 22629800
TI  - [Functional state of the liver in patients, suffering chronic abscess after the
      organ resection].
AB  - The results of treatment of 55 patients, in whom hepatic resection was performed
      in 2004-2011 yrs, were analyzed. In 30 patients (main group) various kinds of
      hepatic resection was done for chronic abscess of the organ; in 25 (control
      group)--hepatic resection was conducted for hepatic tumors. In both groups o
      patients a comparative estimation of hepatic functional state after the organ
      resection was conducted in accordance to albumin level in the blood serum, the
      coagulogram indices, integral ration of transferases activity and a bilirubin
      content. There was proved, that a hepatic functional state disorders after its
      partial resection in patients, suffering chronic hepatic abscess, are similar to
      those in tumoral hepatic affection.

PMID- 22629801
TI  - [Biofunctional symmetry of individual values of clinic-laboratory indices in
      patients, suffering severe forms of an acute pancreatitis].
AB  - Individual values of clinic-laboratory indices were analyzed in 125 patients,
      suffering severe forms of an acute pancreatitis (AP). In the early postoperative
      period there were analyzed 65 indices: clinical analysis of the blood, 24
      hematological indices, biochemical analysis of the blood, coagulogram, estimates
      according to the ASSES, APACHE II, SAPS, SAPS II, SAPS III scales. There was
      established, that in 83.1% of patients in severe forms of an AP the ratio or the
      values difference of clinic-laboratory indices in dynamics of postoperative
      period are depicted according to the "Golden section" rule with deviation no more
      than 10-15%. In the patients, suffering sterile pancreonecrosis, in comparison
      with those, suffering infected pancreonecrosis and in the patients with infected
      pancreonecrosis without retroperitoneal space cellular tissue affection in
      comparison with patients, suffering infected pancreonecrosis and the
      retroperitoneal space cellular tissue affection there were more signs, the values
      ratio or difference of which have deviated from the "Golden section" rule no more
      than by 5%. While estimating the patients state severity in those, suffering
      severe forms of AP, using special scales, most precisely the coincidence with a
      "Golden section" rule was noted, according to scales ASSES and SAPS III.
      Prognostically unfavorable was a progressive increase of the points sum according
      to ASSES scale in dynamics of postoperative period.

PMID- 22629802
TI  - [Anatomic variants of hepatic artery in metastatic affection of the liver].
AB  - On 39 nonfixed cadavers of patients, in whom hepatic metastatic affection was
      diagnosed in abdominal cavity tumors, there were studied up a hepatic artery
      anatomic variants and possible accesses. In 22 observations there was noted a
      typical variant of hepatic artery branching from a. hepatis communis, in 9-
      isolated blood supply of the left and right hepatic lobes, in 4--additional
      branches of various diameter from a. gastrica sinistra to the left hepatic lobe,
      in 2-- additional branches toward the right hepatic lobe, branching from a.
      mesenterica superior, in 1--the blood supply of the left hepatic lobe by arterial
      branch from splenic artery, while a lienalis-hepatic trunk have branched from
      truncus coeliacus. In one observation there was revealed the common hepatic
      artery branching on three trunks, while the median one have supplied a hepatic
      quadrate lobe. It is expedient in all observations perform en bloc lymph node
      dissection of hepatic hilus with the truncus coeliacus structures opening. The
      proposed order of activities while conduction of selective intraarterial
      polychemotherapy permits to take into account the anatomic variants as well and
      to eliminate the possible faults and complications occurrence.

PMID- 22629803
TI  - [Application of plasmapheresis in postoperative period in patients, suffering
      obturation jaundice].
AB  - Operative intervention, aiming to decompress a biliary system in the patients,
      suffering choledocholithiasis, durable obturation jaundice, severe hepatic
      insufficience, gives often poor outcomes, high lethality and high complications
      ratio. Obturation jaundice and hepatic insufficiency, occurring on its
      background, coincide with accumulation of significant quantity of water soluble
      and protein connected toxins in the blood. A patient state improvement, the
      intoxication severity reduction, objectively confirmed by bilirubin level
      lowering in the blood, the transaminases and alkaline phosphatase activity
      lowering were noted under the influence of plasmapheresis application.

PMID- 22629804
TI  - [Intraoperative complications during performance of laparoscopic
      cholecystectomy].
AB  - During 10-year period (2001-2010) in the clinic there were operated on 3648
      patients, suffering cholelithic disease. Most frequent intraoperative
      complications, especially in an acute calculous cholecystitis, were: hemorrhage
      from the bed of gallbladder and its artery, bile leakage, common biliary duct and
      internal organs damage. A casuistic case was depicted--the rubber tube migration
      from the wound into the intestinal lumen and its exile per vias naturalis. The
      authors consider, that aiming to warn the operative complications during
      performance of laparoscopic cholecystectomy, the operation must be performed by
      surgeons, experienced in laparoscopic surgery.

PMID- 22629805
TI  - [The ileocoecal valve changes in chronic constipation in children].
AB  - There were analyzed the results of treatment of 574 children, suf fering anatomic
      anomalies of a large bowel, in whom a chronic constipation was revealed. In 61
      patients the ileoceocal valve (IV) insufficiency was noted. To all the patients
      together with complex conservative treatment there was prescribed a preparation,
      containing magnesium orotat, for restoration of the IV insufficiency. In 56
      (91.8%) patients conservative treatment was effective and in 5--surgical
      intervention was conducted as a consequence of ineffective conservative
      treatment. Negative correlation dependence was established between a patient age
      and results of treatment.

PMID- 22629806
TI  - [Iatrogenic damage of the main vessels].
AB  - The results of treatment of 55 patients, suffering iatrogenic damage of the main
      vessels, which constitute 22.4% of all damages of vessels occurred during last
      ten years, were analyzed. The causes of the vessels iatrogenic damage were
      analyzed in detail. A favorable result achievement, a vessel integrity
      restoration with maintenance of the vascular tube passability have become
      possible in 50 (90.9%) patients due to early and technically adequate operation
      conduction. The extremity amputation was performed in 2 (3.6%) patients, 3 (5.5%)
      patients died.

PMID- 22629807
TI  - [Peculiarities of diagnosis and treatment of varicothrombophlebitis of the lower
      extremities].
AB  - In a vascular surgery clinic there were treated 148 patients, suffering ascending
      thrombophlebitis--varicothrombophlebitis, in 2009-2010 yrs. Varicose diseases
      have lasted from 7 to 32 years. Among instrumental methods of investigation there
      was used ultrasound color angioscanning for diagnosis of varicothrombophlebitis.
      Flotating thrombus was revealed in 7 (4.7%), juxtawall one--in 73 (49.4%) and the
      occlusive one--in 68 (45.9%) patients. There were operated on 130 (87.8%)
      patients, including those in emergency--119 (91.5%). Radical operation was
      performed in 107 (82.3%) patients.

PMID- 22629808
TI  - [Tactics of treatment for extended burns of various affection depth].
AB  - Investigation was based on analysis of the treatment results of 75 children,
      suffering extended superficial and deep skin burns squared 15-30% of body
      surface. There was proved, that sequence of excision of superficial and deep
      necrotic scab influences the burn disease course. There was elaborated algorithm
      of sequence of the operative treatment stages in patients, suffering extended
      superficial skin burns, coexisting with deep burns, the superficial necrotic scab
      definitely, was excised after trauma and a deep one--in the second stage. The
      superficial and deep necrotic scab excision before 7-9th day after trauma have
      promoted significant reduction of the intoxication syndrome severity, the middle
      molecular mass peptides, indices of peroxidal oxidization of lipids, oxidizing
      modification of proteins, clinical signs of SIRS, rate of septic complications in
      1.75 times, the stationary treatment time of severely ill patients by (7.2 +/-
      1.5) days.

PMID- 22629809
TI  - [A state of inner ear in patients, suffering diabetes mellitus and peculiarities
      of treatment of vestibular dysfunction].
AB  - In patients, suffering diabetes mellitus and peripheral cochleovestibular
      syndrome a method of parameatal introduction of auto stem cells was applied for
      the treatment of vestibular dysfunction and sensoneural hearing loss. The
      clinical examination results have witnessed a positive dynamics of a hearing and
      vestibular functions changes in patients, to whom complex treatment was
      conducted. The method application have permitted to improve or restore a hearing
      and vestibular function, to reduce possibility of the disease progress and
      necessity to readmit the patients into the hospital. The method was recommended
      to use in the patients, suffering diabetes mellitus with vestibular dysfunction
      and sensoneural hearing loss.

PMID- 22629810
TI  - [The diseases, simulating a nodular goiter formation].

PMID- 22629811
TI  - [Dynamics of technical supply of the medical diagnostic service of the Russian
      Federation in 2002-2010].

PMID- 22629812
TI  - [The effect of processing of the focal track of a composite anode on X-ray tube
      characteristics].

PMID- 22629813
TI  - [A transmission-type ionization chamber for monitoring the dose power of an X-ray
      therapeutic apparatus].

PMID- 22629814
TI  - [Development of the acetabular component for an endoprosthesis of the hip and
      knee joints].

PMID- 22629815
TI  - [Steam-thermal oxide coatings for titanium medical implants].

PMID- 22629816
TI  - [A rapid method for determining the passband of the spatial frequency channels of
      the visual system].

PMID- 22629817
TI  - [Blood group typing on the basis of digital imaging of sedimentation of
      erythrocytes and RBC agglutinates].

PMID- 22629818
TI  - [A horn adapter providing extremely high frequency modification of blood for
      treatment of pyoinflammatory complications in surgery].

PMID- 22629819
TI  - [A device for estimating the risk of occurrence of cardiovascular insufficiency
      during exercise stress].

PMID- 22629820
TI  - [Biomedical fiber-optic temperature and pressure sensors].

PMID- 22629821
TI  - [Automated classification of leukocytes in blood smear images].

PMID- 22629822
TI  - [Current approaches to the study of carcinogenic safety, antineoplastic,
      anticarcinogenic and geroprotective effects of various pharmacologic
      preparations].

PMID- 22629823
TI  - [Cutaneous melanoma in the head and neck region: current knowledge].

PMID- 22629824
TI  - [Prognosis for the metastasis of squamous cell carcinoma of the head and neck].

PMID- 22629825
TI  - [Role of human cytomegalovirus in the pathogenesis, growth and aggressiveness of
      prostate cancer].

PMID- 22629826
TI  - [Cervical cancer: morbidity and mortality (population-based study)].

PMID- 22629828
TI  - [Immunologic predictors of diabetes mellitus in menopausal breast cancer
      patients].
AB  - Although the relations between diabetes mellitus (DM) and breast cancer (BC) are
      lately widely discussed, the actual causes for cancer predisposition in patients
      with diabetes are currently unclear. This study was designed to define the
      frequency of DM immunological predictors occurrence and immune system function
      shifts in patients with breast cancer. Sixty four BC patients, 19 patients with
      benign breast conditions and 40 healthy individuals were included. The lymphocyte
      sensibilization with insulin suppressed by prostaglandin-synthesizing cells or
      cells with histamine receptor expression (DM predictor) is more common in BC
      patients than in control group (29 of 56 vs 5 of 37, p < 0.001). This is not a
      tumor marker, but rather is an objective factor reflecting higher occurrence of
      insulin resistance in this group. For BC patients is also characteristic the
      lower PHA-stimulated peripheral lymphocyte proliferation rate probably caused by
      increase in short-lived suppressor cell activity, a usual sign of the impairment
      of cell-mediated immunity. It is also possible, that the immunologic predictors
      of DM associated with insulin resistance, combined with the effects of short
      lived suppressor cells, promote tumor cell proliferation.

PMID- 22629827
TI  - [The influence of metformin and N-acetylcysteine on mammographic density in
      postmenopausal women].
AB  - Mammographic breast density (MBD) value is currently one of the strong predictors
      for mammary carcinoma development. There are also other conditions predisposing
      to MBD increase with hormone-related markers different from those used in breast
      cancer, while pharmacological methods for MBD reduction are few and still
      considered experimental. In the current study 25 postmenopausal women received
      daily for a median 10.5 months 1-1.5 g of antidiabetic biguanide metformin
      (siofor) (n = 14) or 400-600 mg of antigenotoxic drug N-acetylcysteine (n = 11).
      In both groups MBD was measured before and after treatment. The effects of both
      drugs were quite similar. Metformin use lead to lower MBD in 4 of 14 (28.5%)
      women with mean MBD decrease of -1,24% (absolute dynamics) and -5.03% (relative
      value). In N-acetylcysteine group this effect was observed in 27.3% of cases,
      with -2.0% absolute dynamics and -6.1% relative dynamics. In metformin group the
      most evident absolute and relative dynamics was observed in patients with no
      signs of metabolic syndrome, -10.86% compared to -2.45%. In 7 women the metformin
      use also lead to decrease of dense and increase of non-dense areas on digital
      scans, leading to decrease in dense to non-dense area volume ratio. Therefore,
      the similar effects of metformin and N-acetylcysteine are probably explained
      mostly not by insulin resistance elimination by metformin, but by altered cell
      proliferation, apoptosis and DNA repair.

PMID- 22629829
TI  - [Pleomorphic fibrosarcoma].
AB  - 263 tumors diagnosed as malignant fibrous histiocytomas and undifferentiated
      pleomorphic sarcomas have been reassessed morphologically, immunohistochemically
      and ultrastructurally. The diagnosis of pleomorphic fibrosarcoma was made in 19
      patients (5%). The tumors occur in the lower and upper extremities and trunk. The
      patients have a long history of painless intramuscular mass (for a median of 6
      months). Follow up showed disease recurrence in 24% of patients and metastases in
      32% of patients. All tumors consisted of spindle-shaped fibroblasts and
      myofibroblasts with a prominent rough endoplasmic reticulum and Golgi apparatus,
      extracellular collagen fibrils. Variable number of histiocite-like fibroblasts
      and undifferentiated cells were found. No other signs of tumor cell line
      differentiation were noted. A pleomorphic fibrosarcoma and malignant fibrous
      histiocytoma have similar clinical and radiographic manifestation and survival
      rates.

PMID- 22629830
TI  - [The optimal radiation volume after first-line chemotherapy in Hodgkin lymphoma].
AB  - Radiation therapy has evolved from extended-field radiation therapy (EFRT) to
      involved-field radiation therapy (IFRT), reducing toxicity while maintaining high
      cure rates. Recent publications recommend a further reduction to involved-nodal
      radiation therapy (INRT); however, this has not been clinically validated. The
      need for irradiation or optimal radiation volume after chemotherapy are not
      defined. The treatment results of 296 Hodgkin's disease patients receiving ABVD
      or BEACOPP-21 chemotherapy with consequent EFRT demonstrate CR/PR > or = 80% and
      99% local disease control rate. Beam therapy with EFRT is possible to use if dose
      levels don't exceed 30 Gy. Higher doses demands reduction of volume of radiating
      target. In our opinion the optimum program of beam therapy involves 2 stages with
      maximal possible dose level EFRT followed by additional INRT. Those approaches
      offer perspectives for Hodgkin's disease treatment.

PMID- 22629831
TI  - [Role of response to first-line chemotherapy and of the primary lesion in Hodgkin
      lymphoma].
AB  - Based on the results of combined treatment with inclusion of ABVD and BEACOPP-21
      chemotherapy regimens the basic principles of therapy depending on the nodal
      relaps criterium were developed. The most rational approach to treatment results
      evaluation concerns the lesions with the least response to chemotherapy. The
      groups of "adequate" and "inadequate" response to chemotherapy should be formed.
      The initial lesion localisation doesn't play an important part in the modern
      chemotherapy settings and should not be concerned while choosing tactics of
      radiation therapy. The method described should interest oncologists and
      radiologists involved in the treatment of Hodgkin lymphoma.

PMID- 22629832
TI  - [The role of transcription factor Snail1 in the regulation of hormonal
      sensitivity of in vitro cultured breast cancer cells].
AB  - The loss of hormonal dependency in breast tumor cells is often accompanied by
      epithelial-mesenchymal transition (EMT) features and an increase in cell
      metastasizing and invasiveness. Here we studied the role of transcription factors
      Snail1--the central mediator of EMT, in the progression of hormonal resistance of
      breast cancer cells. The experiments were performed on the estrogen receptor(ER)
      positive estrogen-dependent MCF-7 breast cancer cells, ER-positive estrogen
      resistant MCF-7/LS subline generated through long-term cultivation of the
      parental cells in steroid-free medium, and ER-negative estrogen-resistant HBL-100
      breast cancer cells. We found that decrease in the estrogen dependency of breast
      cancer cells is accompanied by an increase in Snail1 expression and activity, and
      demonstrated the Snail1 involvement in the negative regulation of ER. NF-kappaB
      was found to serve as a positive regulator of Snail1 in breast cancer cells, and
      simultaneous inhibition of NF-kappaB and Snail1 by RNA interference resulted in
      marked increase of cell response to antiestrogen tamoxifen. In general, the
      results obtained demonstrate that direct inhibition of NF-kappaB and Snail1
      partially restores the estrogen receptor machinery, and show that Snail1 and NF
      kappaB may serve as an important targets in the treatment of breast cancer.

PMID- 22629833
TI  - [Combined effect of quercetin and indralin (B-190) in alleviating carboplatin
      hematologic toxicity].
AB  - In experiment conducted on male mice of C57B1/6 line quercetin (80-100 mg/kg
      injected 60 minutes before carboplatin) or an emergency radioprotector indralin B
      190 (50-100 mg/kg injected 5 minutes after carboplatin) decreased the mortality
      of animals from toxic carboplatin dose of 100 mg/kg from 40% to 10-11% (p <
      0.05). In mice receiving both quercetin and B-190 the reduction of carboplatin
      toxicity evaluated by blood WBC level was even more prominent (p < 0.05). The
      results were confirmed in rat experiment. In animals receiving both quercetin and
      B-190 with 50 mg/kg of carboplatin the WBC level was higher (p < 0.05). Quercetin
      alone had no effect on hematologic toxicity in those settings. Besides, quercetin
      and B-190 didn't have any effect on RBC level changes.

PMID- 22629834
TI  - [Hematoprotective effectiveness of dicarbamin in experimental post-radiation bone
      marrow syndrome].
AB  - The effect of dicarbamin on cellular composition of rabbits' venous blood in
      experimental post-radiation bone marrow syndrome was studied. The dicarbamin use
      has allowed to reduce depth and to shorten the duration of post-radiation
      leukocytopenia.

PMID- 22629835
TI  - [Effectiveness of different castration methods in breast cancer patients].
AB  - Estrogens play the most important role in breast cancer oncogenesis. There are
      different methods used to decrease estrogen production and serum concentration:
      surgery, irradiation and drug-based method. In the current study 500 patients
      with localized surgically resectable breast cancer (infiltrative-edematous form
      included) or disseminated breast cancer with indication for ovarial function
      inhibition. The patients were divided into 3 groups. The first group consisted of
      400 patients with prior endoscopic bilateral ovariectomy. The second group
      included 50 patients with prior ovarian irradiation, the third one included 50
      patients after laparotomic ovarian resection. The results obtained show 100%
      effect of endoscopic ovariectomy resulted in disabled ovarian function, which is
      more effective, than ovarian irradiation (92%). Besides, the endoscopic method
      doesn't have negative effects characteristic for irradiation, such as involvement
      of non-target organs or restoration of hormone production. Endoscopic surgery was
      characterized by 10-fold decrease in complications rate compared to laparotomic
      operation (2.2% vs 24%). Besides, endoscopic intervention leads to much shorter
      inpatient treatment duration and demand for anesthetics and antibiotic treatment
      making it less costly, than more traditional methods of castration. Therefore,
      endoscopic ovarian resection is a safe and effective castration method in breast
      cancer patients.

PMID- 22629836
TI  - [Anesthetic management in endotracheo-bronchial surgery for central bronchial and
      tracheal tumors].
AB  - The article summarizes the experience of anesthetic management in rigid
      bronchoscopy endobronchial surgery. Induction intravenous anesthesia followed by
      high tidal-volume mechanical ventilation proved to be more effective, than
      inhalation anesthesia with injector or high-frequency ventilation, although these
      methods are safe and effective in patients with compensated respiratory failure.
      The use of controlled hypotonia with mean arterial pressure of 60-70 mm Hg leads
      to decrease of blood loss and hypoxemia prevention without impairment of
      hemodynamics.

PMID- 22629837
TI  - [Clinico-morphological properties and surgical treatment results in
      retroperitoneal liposarcomas].
AB  - The separate clinico-morphological features of nonorganic retroperitoneal
      liposarcoma (NRL) and their prognostic value were studied in 200 patients. The
      type of primary NRL is histologically erentiated in 65.5%, myxoid in 16.1%,
      dedifferentiated in 9.2%, pleomorphic in 4.6% and mixed in 2.3%. There is a
      positive elation between overall survival, lyposarcoma hystologic type < 0.007)
      and completeness of tumor resection (p < 0.0008). Differentiated and myxoid NRL
      with cell volume less than 5.0% are characterized by better prognosis. Myxoid NRL
      with cell volume more than 5.0%, dedifferentiated and pleomorphic NRL types are
      unfavorable prognostic factors. Radical surgical resectio leads to 5-year and 10
      year overall survival of 57.5% and 7.8%. Palliative surgery lead to worse results
      with 3-year and 5-year overall survival of 50.0% and 31.8% respectively.
      Therefore, the most important prognostic factors in NRL are histological type and
      completeness of resection.

PMID- 22629838
TI  - [Primary refractory and relapsed Hodgkin lymphoma with unfavorable prognosis].
AB  - In this retrospective clinical study 100 patients with primary unfavorable
      prognosis stage II Hodgkin lymphoma (HL) (n = 50) or stage IV HL (n = 50). The
      ABVD chemotherapy allowed to achieve remission in 90% of cases with 5-year
      relapse-free survival (RFS) and overall survival (OS) of 64% and 92%, the basic
      BEACOPP regimen lead to the same 90% remission rate with 74% DFS and 94% OS.
      These results for ABVD and basic BEACOPP regimens are characterized by similar
      statistic values (p = 1.0; p = 0.6; p = 0.9), although the use basic BEACOPP lead
      to statically valid decrease of grade III-IV toxicity (p = 0.005). The occurrence
      of primary refractory HL was slightly higher in basic BEACOPP group (18% versus
      10% in ABVD group), although this difference had no statistical value (p = 0.3)
      and was probably due to higher number of patients with > 1 extranodal
      localizations. The occurrence of primary refractory HL correlated to disease
      stage: 6% in stage II and 22% in stage IV (p = 0.04). HL relapse frequency in
      ABVD and BEACOPP groups was similar (12% and 8%), there was no statistically
      valid difference (p = 0.5). In ABVD and basic BEACOPP recipients with stage II/IV
      HL the primary refractory disease rate was 15%, relapse rate was 10%. Five-year
      OS in primary refractory and relapsed patients was lower, than in general patient
      population (64% and 70% compared to 80%), although the difference had no
      statistical significance (p = 0.6, p = 0.7).

PMID- 22629839
TI  - [Use of Reamberin for the prevention of adverse effects of combined
      antineoplastic agents in stage III-IV ovarian cancer during induction treatment].
AB  - Ovary cancer treatment often presents clinical promlems due to frequent occurence
      of late diagnostics (III-IV stages), severe treatment complications in patients
      with ascitis and tumor intoxication. Reamberin can be used as supportive therapy
      aimed at decrease of intoxication, which is one of the main hindrances for
      antitumor therapy. In the current study reamberin was used in 89 stage III-IV
      (FIGO) ovary cancer patients with ascitis, age 42 to 79, CP or CAP chemotherapy
      recipients after prior cytoreductive surgery. The occurrence of hematological
      complications (grade 1-2 anemia and neutropenia) and cardiac dysfunctions in the
      study group was much lower, than in the control group. This difference is
      statistically valid (p < 0.01 and p < 0.05). The patients receiving reamberin
      prior to chemotherapy or during chemotherapy rarely (in 3.7% of cases) displayed
      raised creatinine values. In the control group grade 1-3 renal impairment was
      observed in 41.4% cases, in 12 cases the therapy had to be ceased. This
      difference between the groups is statistically valid (p < 0.001). Patients
      receiving reamberin displayed more rapid rate of CA-125 tumor marker serum
      concentration decrease. Therefore, reamberin is an effective drug for prevention
      of chemotherapy side effects and alleviation of intoxication allowing the more
      rigid chemotherapy schedule without an increase in toxicity.

PMID- 22629840
TI  - [Strontium chloride (89Sr-chloride) fractional injection method for bone
      metastases treatment].
AB  - The study was designed to compare the effectivnes of 89Sr-chlorid injections by
      50 Mbk fractions with standard 150 Mbk injection in patients with bone
      metastases. Fifty patients with bone metastases were included in the study, 25 of
      them received 89Sr-chloride by fractional and 25 (control group) by single
      injection. The pain intensity, white blood cells and thrombocytes concentration
      values were evaluated in both groups before and after treatment. The study proved
      the possibility of using systemic 89Sr-chloride fractional radiotherapy in
      patients with bone metastases and concurrent stage 2-3 myelosupression. The
      method of fractial 89Sr-chloride injection is effective in symptomatic treatment
      of patients with bone metastases.

PMID- 22629841
TI  - [Nikolai Nikolaevich Petrov: Evolution of oncology in Russia].

PMID- 22629842
TI  - [Application of robotized radiosurgical system CyberKnife for the treatment of
      neurosurgical patients].
AB  - Robotized system for radiosurgery CyberKnife (Accuray Inc., USA) is the first
      device dedicated and optimized for advanced irradiation during 1-7 fractions
      (i.e. radiosurgery and hypofractionation). CyberKnife is characterized by
      elaborate guidance system, high precision of dose delivery, possibility of
      conformal dose distributions with high gradient of target borderline dose which
      is most important in proximity of critical structures. The first CyberKnife
      system in Russia was installed in Burdenko Neurosurgery Institute. The paper
      presents 2-year experience of treating patients using CyberKnife. From April 2009
      till October 2011 896 patients were treated using CyberKnife. Mean age was 48
      years. Overall number of sessions was 2626. Radiosurgical procedures were
      performed in 21.8% of patients. 91% of cases were treated for intracranial
      lesions. Limited follow-up period in all kinds of pathology demonstrated results
      consistent with standard fractionation or radiosurgery. The rates of observed
      complications were also comparable with accepted techniques. CyberKnife system
      plays significant role in everyday activity of department of radiation therapy.
      In careful and thorough selection of patients it allows efficient and high
      quality treatment of patients with neurosurgical diseases.

PMID- 22629843
TI  - [First experience of stereotactic radiation therapy for vestibular schwannoma
      using CyberKnife].
AB  - Currently stereotactic radiosurgery has become the treatment of choice in small
      vestibular schwannomas. This paper discusses our first experience of application
      of CyberKnife system for stereotactic irradiation of these tumors. From April
      2009 till June 2011 we treated 62 patients (35 female and 27 male) with
      vestibular schwannomas. Stereotactic radiosurgery using CyberKnife system was
      performed in 33 patients. Mean tumor volume was 2 +/- 1.4 cm3. Hypofractionated
      treatment was used in 30 cases (31 tumor). Mean tumor volume reached was 7 +/-
      6.2 cm3 (range - 0.5-31.3 cm3). In a case of a patient with NF2 simultaneous
      irradiation of bilateral tumors was performed. Most frequently we applied 3
      fractions 6 Gy each (17 observations of 31, or 55%) and 5 fractions with mean
      dose 5 Cy (10 cases, or 32%). Follow-up period varied from 1 to 26 months (mean 9
      +/- 4.5 months). By the end of this study (June 30, 2011) surgical resection was
      required in the only case of 47-years old male patient with cystic schwannoma of
      left vestibular nerve 5 months after radiation treatment, due to progressive
      growth of the cyst and increased brainstem compression. Tumor growth control was
      established in 97.5% of cases. Stabilization of auditory function was achieved in
      77.5% of series. Effective hearing was preserved in 75% of patients. Facial nerve
      palsy after stereotactic radiation treatment was observed in 2 cases (3%).
      Incidence of trigeminal nerve dysfunction was significantly higher: sensation
      disturbances occurred in 6 (10%) patients: 3% after radiosurgery and 16.7% after
      hypofractionation. We did not obtain significant correlations between risk of
      cranial nerve complications and dosimetric or demographic factors. However we
      observed stable tendency: larger initial volume of the tumor and presence of
      trigeminal nerve dysfunction before treatment were poor prognostic factors for
      trigeminal neuropathy. Stereotactic irradiation using CyberKnife system is
      effective and sufficiently safe technique for management of vestibular
      schwannoma. The paper demonstrates high rates of tumor stabilization, hearing
      preservation and minimal incidence of complications associated with trigeminal or
      facial nerve.

PMID- 22629844
TI  - [Early results of irradiation of intracranial meningiomas using CyberKnife].
AB  - Meningiomas are frequently diagnosed intracranial lesions which cannot be
      resected radically in the majority of cases. Traditional radiotherapeutical
      techniques allow control of tumor growth in such situations. CyberKnife system
      may be used for radiosurgery and in sight hypofractionation. During 27 months 231
      patient with intracranial meningiomas of different localization was treated in
      department for radiation therapy of Burdenko Neurosurgical Institute using
      CyberKnife system (Accuray Inc., USA). Mean age was 53 years. 55% of patients
      underwent previous surgical treatment, and diagnosis of meningioma was
      histologically verified. In 231 patient 374 targets were irradiated. Mean volume
      of irradiation reached 15.8 cm3 (range - 0.73-108.5 cm3). In 89% of cases
      hypofractionated therapy was used, in 10.1% we performed radiosurgery.
      Catamnestic data were available in 80 patients. Mean follow-up period was 11.6
      months (6-27 months). Control of tumor growth was established in 100% of cases
      with WHO grade I tumors, in 66.7% of WHO grade II tumors and 60% in WHO grade III
      tumors. Deterioration after radiation treatment was observed in 16% of cases of
      75 with control of tumor growth. In 8 cases worsening was due to radiation
      induced reactions verified by MRI studies. Radiosurgical and hypofractionated
      treatment of meningiomas using CyberKnife is actual and highly-effective
      technique. Further investigations are needed to determine optimal standards of
      hypofractionated radiotherapy of meningiomas.

PMID- 22629845
TI  - [First experience of CyberKnife stereotactic radiotherapy for glomus jugulare
      tumors].
AB  - Glomus jugulare tumors (GJT) (AKA paraganglioma or chemodecroma) make 0.6% of
      head and neck tumors and 80% of jugular foramen lesions. Recently different types
      of stereotactic radiotherapy are actively used in their treatment. The given
      paper summarizes our first experience of using CyberKnife system in management of
      patients with paragangliomas. Since April 2009 till September 2011 34 patients
      with GJT were treated in department for radiation therapy of Burdenko
      Neurosurgical Institute using CyberKnife system. Mean age was 50.5 years (range
      26-75 years). Mean volume of treated lesions was 14.6 +/- 10.96 cm3 (range--1.04
      37.4 cm3). Stereotactic radiosurgery was performed in 4 patients. Mean prescribed
      dose was 17 +/- 3.1 Gy (13.7-22 Gy). 30 patients received hypofractionation
      treatment (3-7 fractions with total dose 18-35 Gy). Mean follow-up period in our
      series was 8 months (1-20 months). Control of tumor growth reached 100% because
      none of the patients needed any additional therapy (microsurgical resection or
      repeated radiotherapy). Persistent trigeminal neuropathy was observed in 1 case
      (5%). There were no constant impairment of VII, IX, X, XII and XIII cranial
      nerves in the series. Stabilization of auditory function was present in 9 (82%)
      of 11 patients with initially preserved hearing. Preservation of effective
      hearing was observed in 75% of patients. Stereotactic radiosurgery and
      hypofractionation using CyberKnife system are effective modalities in management
      of such complex neurosurgical disease as GJT. Neurological deterioration after
      radiation treatment is extremely rare and in most cases is transient.

PMID- 22629846
TI  - [Stereotactic radiotherapy for cerebral metastases using CyberKnife].
AB  - During recent decade development of frameless techniques of fixation enabled
      introduction of stereotactic radiation therapy in metastatic brain lesions and
      made possible irradiation of large foci involving or proximal to eloquent and
      critical brain areas. This paper focuses on comparative analysis of effectiveness
      of hypofractionation (HRST) and radiosurgery (SRS) using CyberKnife system in
      cerebral metastases. Since November 2009 till June 2011 54 patients with cerebral
      metastases were treated using CyberKnife system. Age of patients ranged between
      25 and 77 years (mean 54 years). 16 patients received radiosurgical treatment
      (mean total dose was 22.5-35 Gy, number of fractions varied from 2 to 7, mean
      volume of irradiation was 22.69 cm3) and 8 patients were treated by HRST with RS
      of selected foci (mean total dose reached 23 and 30 Gy, mean volume of
      irradiation was 1.02 cm3 and 11.19 cm3, respectively). Indices of overall
      regression and stabilization of disease for HRST and SRS groups were 81% and 79%,
      respectively. With mean follow-up period of 12.3 (1-16.1) months median survival
      for SRS and HRST reached 6.38 (1-15.8) and 6.2 (0.2-16.1) months and median
      recurrence-free survival was 3.6 (1-13.6) and 5.5 (2-14.2) months, respectively.
      Obtained results confirmed biological advantages of fractionated stereotactic
      radiotherapy of large cerebral tumors in comparison with radiosurgery.
      Prospective studies with rigid criteria of inclusion are required to determine
      optimal dose/volume/fractionation interrelations in stereotactic radiation
      treatment of cerebral metastases.

PMID- 22629847
TI  - [First experience of radiosurgical treatment of arteriovenous malformations using
      CyberKnife].
AB  - Radiation treatment techniques are essential in complex management of selected
      neurooncological, neurovascular and functional brain pathology. Stereotactic
      radiotherapy provides sufficient damage to the target (tumor, AVM, functional
      structures) with minimal impact on surrounding brain tissue. Development of
      stereotactic methods with X-ray guidance lead to expansion of indications for
      irradiation of intracranial and extracranial lesions. This paper represents the
      first experience of treating patients with AVMs using CyberKnife system in
      Russia. The technique of stereotactic radiotherapy (SRT) and radiosurgery (SRS)
      is described in details, as well as indications for SRT and SRS in different
      regiment of fractionation, possibilities of planning systems, with additional
      emphasis on specific complications, radiation-induced reactions and capabilities
      of neurovisualization methods in evaluation of radiation-induced damage of brain
      tissue.

PMID- 22629848
TI  - [CyberKnife stereotactic radiotherapy for mass lesions of the spinal cord and
      spine].
AB  - Introduction of a novel technology of stereotactic radiation treatment using
      linear accelerators, refining of systems for visualization and guidance provided
      rapid development of extracranial radiosurgery. Nowadays there is a possibility
      of precise stereotactic irradiation of lesions with different size and
      localization. One of the most actual and promising indications for radiosurgery
      are different primary and metastatic lesions and arteriovenous malformations of
      spinal cord and spine. Radiosurgery and hypofractionated radiotherapy with
      precise dose delivery during one or several sessions allow effective and safe
      treatment of neoplasms with any degree of radioresistance. This paper contains
      analysis of the first Russian experience of stereotactic radiation treatment of
      lesions of spinal cord and spine using robotized system CyberKnife (Accuray Inc.,
      USA).

PMID- 22629849
TI  - [Stereotactic radiotherapy and radiosurgery in treatment of patients with deep
      seated pilocytic astrocytomas].
AB  - Pilocytic astrocytoma (PA) is a low-grade glial tumor (WHO grade I) with
      predominant occurrence in pediatric patients. According to many authors,
      stereotactic radiosurgery (SRS) and radiotherapy (SRT) promote long-term
      remission or retardation of tumor progression in patients with in inoperable
      lesions after incomplete resection or recurrence. Therefore it is essential to
      determine the role of SRS and SRT in complex management of patients with deep
      seated PA. Since April 2005 till May 2010 101 patient with intracranial PA was
      treated in department for radiation therapy of Burdenko Neurosurgical Institute.
      The series consisted of 70 pediatric patients (below 17 years inclusively) and 31
      adults, of them--51 male and 50 female patients. Mean age was 15.1 years (9.8
      years in children and 28.7 in adults). In 90 patients (89.2%) tumors were
      previously histologically verified (tumor resection in 83 cases and biopsy in 7).
      In 11 (10.8%) patients diagnosis of PA was based on clinical and
      neurovisualization data. In most cases SRT (66 (66.3%) patients) was preformed,
      the rest 35 (34.7%) patients were treated by SRS. Median follow-up from the onset
      of disease reached 52 months (2-228 months). Catamnestic data were available in
      88 (87%) patients. By the end of catamnestic follow-up (December 2010) 87 (98.8%)
      patients treated by SRS and SRT were alive. Median follow-up from the start of
      radiation treatment was 22.7 months (6-60 months). Progression of tumor was
      observed in 20 patients (22.7%), in 18 of them due to cyst growth. 18 patients
      were reoperated. In 12 operated patients histological examination and its
      comparative analysis were performed. We found that alterations in the tumor
      tissue, accompanied by regression of solid component and progression of cystic
      portion, represent reactive-degenerative changes in the tumor as a consequence of
      radiation-induced pathomorphism. SRS and STR are effective techniques for
      treatment of patients with primary and recurrent PA despite regardless of
      localization of the tumor. There procedures should be performed shortly after non
      radical resection. Control of tumor growth by the present time (median follow-up
      is 22.7 months) reaches 98%. "Progression" of the tumor due to enlargement of
      cystic portion shortly after SRT and SRS represents reactive-degenerative
      alterations in the tumor tissue and should not be evaluated as true recurrence;
      without neurological deterioration these cases do not require special treatment.

PMID- 22629850
TI  - [CyberKnife stereotactic radiosurgery in the treatment of patients with
      trigeminal neuralgia].
AB  - Trigeminal neuralgia (TN) is a disabling disease with severe impairment of
      quality of life and everyday activity of patients. Range of treatment modalities
      is wide and includes conservative therapy, surgical methods and stereotactic
      radiosurgery (SRS). SRS is a minimally invasive technique which provides good
      results and minimal rate of complications. High geometrical and clinical
      precision of frameless SRS using CyberKnife system allows its application in TN
      when high dose is delivered to a small volume. The given paper focuses on the
      first Russian experience of frameless SRS of TN using robotized system
      CyberKnife. Since April 2009 till June 2011 4 patients with TN were treated in
      department for radiation therapy of Burdenko Neurosurgical Institute using
      CyberKnife system. Mean age was 63 years. Mean and maximal target dose reached 70
      and 90 Gy, respectively. Data of catamnestic clinical examination were available
      in all 4 patients. Follow-up period reached 8 months. Response to treatment was
      observed in all cases. In 2 (50%) patients full effect was reached while in the
      rest only partial effect was present. No complications were encountered.
      Effectiveness and safety of SRS using CyberKnife system is comparable with framed
      SRS.

PMID- 22629851
TI  - [Application of SPECT/CT in neurosurgical practice].
AB  - The paper presents the experience of application of single-photon emission
      computed tomography (SPECT) and CT in neurosurgery. Combination of these two
      techniques in the single system provides higher precision of both methods. The
      novel technique allows assessment of tumor spread in the brain, differential
      diagnosis of tumor regrowth and radiation-induced necrosis, evaluation of
      cerebral perfusion in epilepsy, traumatic brain injury (TBI), and diagnostics of
      secondary CNS lesions. Examples of primary diagnosis, dynamic follow-up and
      differential diagnosis of cerebral neoplasms, localization of epileptogenic foci
      in planning of surgery, prediction of outcome after TBI and evaluation of spread
      of metastatic skeletal involvement and further application of acquire data are
      presented.

PMID- 22629852
TI  - [Stereotactic radiation treatment of patients with cerebral arteriovenous
      malformations].

PMID- 22629853
TI  - [Theory of transition state between norm and pathology].
AB  - In experiments on animals (rodents, carnivores, primates), using the methodology
      of situational conditioned reflexes, a model of the transition state between norm
      and pathology of humans has been created. We studied the problems that are not
      available to deal with on a person for technical and ethical reasons. Specific
      features of manifestation of the transition state, its central mechanisms and
      biological role were discovered. We found out bifunctional nature of the
      transition state--biologically positive, protective and biologically negative,
      like the state immediately preceding stable disease. It was established that in
      the ascending evolutionary series the increase in role and complexity of
      mechanisms of the positive component of the transition state occur. This fact can
      be explained by the development of adaptive activity of the brain, responding to
      the complex informational environment and, in particular, to so called
      "informational triad" (a combination of three factors - the amount of
      information, a factor time and level of motivation). We revealed "asymptomatic"
      phenomena of the transition state and showed its role in the development of
      pathology. A theory of the transition state was formulated as a summation of
      knowledge and hypotheses about the phenomena occurring in the body in response to
      a pathogenic stimulus. We proposed the classification of the transition state as
      a phenomenon, value of which is corresponding to the rate "norm - illness -
      clinical death", i.e. considering it in the rank of major states of the organism.

PMID- 22629854
TI  - [Subpopulation structure of T-regulatory cells and proliferative response of
      blood lymphocytes in vitro under pulmonary tuberculosis].
AB  - Subpopulation structure of T-regulatory cells and proliferative activity of blood
      lymphocytes in vitro in patients with different clinical forms of pulmonary
      tuberculosis were studied in this work. It has been shown that Trn--natural T
      regulatory lymphocytes (CD4+CD25+Foxp3+) play a leading role in formation of
      immune suppression under infiltrative, disseminated and fibrosis-cavernous
      pulmonary tuberculosis. Besides, their number is increased in blood of both
      tuberculin-positive and tuberculin-negative patients. Negative correlation
      between the number of Trn and proliferative activity of blood lymphocytes (basal,
      mitogen- and antigen-induced)has been established, which testifies about
      participation of Trn in suppression of lymphocyte proliferation and Th1- and Th2
      immune response.

PMID- 22629855
TI  - [Effect of myelopeptides on reactive oxygen species generation and IL-1beta and
      TNF-alpha production by peripheral blood cells].
AB  - Myelopeptides MP-3, MP-5, and MP-6 were found to suppress zymosan-induced
      production of reactive oxygen species by leukocytes both under one-way
      introduction and under pretreatment. All of myelopeptides under examination in
      case of one-way introduction in cultures with zymosan demonstrated a decrease in
      zymosan-stimulated (1500 mkg/ml) production of IL-1beta, and activation of
      spontaneous production of this cytokine by whole blood cells. TNF-alpha
      production under myelopeptide effect was lowered in cultures with 150 mkg/ml
      zymosan. Under pretreatment myelopeptides did not render effect on IL-1beta and
      TNF-alpha production, with the exception of single stimulating effect of MP-5 on
      IL-1beta level in spontaneous cultures. Using comparative analysis the difference
      in direction and expressivity of effects of various myelopeptides was not
      revealed that suggests the existence of common mechanism of action in this group
      of peptide bioregulators.

PMID- 22629856
TI  - [Role of restricted nitric oxide overproduction in the cardioprotective effect of
      adaptation to intermittent hypoxia].
AB  - Adaptation to intermittent normobaric hypoxia is cardioprotective and can
      stimulate nitric oxide (NO) synthesis. However the role of nitric oxide (NO) in
      prevention of ischemia-reperfusion (IR) injury of myocardium is controversial.
      This study was focused on evaluating the effect of adaptation to hypoxia and IR
      on NO production and development of nitrative stress in the myocardium.
      Adaptation to hypoxia tended to increase NO production, which was determined by
      the total level of plasma nitrite and nitrate, and prevented IR-induced NO
      overproduction. The IR-induced NO overproduction was associated with significant
      3-nitrotyrosine (3-NT) accumulation in the left ventricle but not in septum or
      aorta. In hypoxia-adapted rats, 3-NT after IR was similar to that of control rats
      without IR. IHC induced marked accumulation of HIF-1alpha in the left ventricle.
      We suggest that HIF-1alpha contributes to NO-synthase expression during
      adaptation to hypoxia and thereby facilitates the increase in NO production. NO,
      in turn, may subsequently prevent NO overproduction during IR by a negative
      feedback mechanism.

PMID- 22629857
TI  - [Activity of the NO-system in lung after pulmonectomy of various volumes].
AB  - The study was designed to evaluate the activity of NO-system in lung after
      resection of various volumes. White male rats, subjected to left or right
      pulmonectomy, were used. Activity of the NO-system in lung was estimated as a
      difference in the contents of its metabolites (nitrates NO3(-) and nitrites NO2(
      )), peroxynitrite (ONOO(-)), activity of endothelial (eNOS) and induced enzyme
      (iNOS), in arterial and venous blood for 3, 7, 14 day after pulmonectomy. It was
      revealed, that with the increase of a resections volume, activity of NO-system
      was reduced. Difference in parameters of NO-system activity in arterial and
      venous blood reflects endothelial dysfunctions in lung, and can be used as
      diagnostic criterion.

PMID- 22629858
TI  - [Cultured cell systems for revelation of new drugs antiatherosclerotic effects
      and their mechanisms investigation].
AB  - Cultured cell models have been developed to study the cholesterol efflux from the
      arterial wall as an integral indicator of reverse cholesterol transport. The
      models and the results of in vivo and ex vivo experiments can be used to propose
      new antiatherosclerotic drugs and elucidate their mood of action.

PMID- 22629859
TI  - [Apoptosis modulation by PMA occurs independently of TsPO expression in squamous
      cell carcinoma cells].
AB  - Phorbol esters are known to modulate protein kinase C activity - enzyme involved
      in cell proliferation, differentiation and apoptosis regulation in skin cells.
      Besides it phorbol-12-myristate 13-acetate was shown possible to modulate
      promoter activity of TsPO - protein that is involved in steroidogenesis and cell
      proliferation regulation. Caspase-3 and TsPO expression was measured in squamous
      cell carcinoma cells after incubation with phorbol-12-myristate 13-acetate and
      ultraviolet radiation. Following alterations of TsPO and caspase-3 levels are
      explained by different mechanisms of regulation.

PMID- 22629860
TI  - [Significance of pain sensitivity for the resistance to immobilization stress].
AB  - The effects of immobilization stress (immobilization on back within 4 h) on the
      functional indexes of Wistar male rats differing with pain sensitivity in the
      tail-flick test were studied. The acute immobilization stress in rats with high
      pain sensitivity compared with low pain sensitivity animals produced the most
      changes of the main functional systems. The high pain sensitivity rats
      demonstrated more significant hypotension, bradicardia, temperature shift,
      decrease of breath frequency and oxygen consumption, acid-alkaline equilibrium
      disorders with lactate acidosis signs. Therefore, the rats with low pain
      sensitivity possess the high resistance to acute stress exposure in comparison
      with high pain sensitivity animals. This confirms the important significance of
      individual pain sensitivity for the formation of stress resistance.

PMID- 22629861
TI  - [The features of bulbo-spinal serotoninergic reaction in the young rats under the
      condition of acute somatic paiN].
AB  - Postnatal changes of background and stress-induced (by electric skin nociceptive
      irritation) concentrations of serotonin (S) and 5-oxyindolacetic acid (5-OIAA)in
      medulla oblongata and in spinal marrow was investigated using the male white rats
      (2-4, 17-18 and 30-35 days old). In the intact rats of these three groups the
      differences of S concentration in medulla oblongata were not revealed. S
      concentration in spinal marrow and 5-OIAA concentrations in both structures were
      changed in phase: decreased during vision-appearing period and increased during 1
      month age. Rats of three groups showed the following reactions to the pain: 2-4
      day rats - increase of spinal pool of S and 5-OIAA and decrease of 5-OIAA
      fraction in medulla oblongata; 17-18 day rats - hypo-S-shift in both structures,
      decrease 5-OIAA in spinal marrow and its increase in medulla oblongata; 30-35 day
      rats - pronounced reduction of both S and 5-OIAA at a bulbo-spinal level.
      Mechanisms of revealed postnatal changes of S metabolism in CNS and their role in
      age features of pain sensitivity formation in early ontogenesis were discussed.

PMID- 22629863
TI  - [Research of interrelations of persistention-factors for sexual-transmitted
      infections].
AB  - Two and more of sexual-transmitted infections present in most quantity of cases
      with persistent form of infection, then with transitory form of infection.
      Activation of immune system with papilloma-virus infection do initiality for
      elimination of virus from organism and stopped next development of infection in
      organism, development of oncologic diseases, persistent of virus in organism.

PMID- 22629862
TI  - [Stimulation of D2-receptors improves passive avoidance learning in female rats].
AB  - The involvement of D2-receptors in learning/memory processes during ovary cycle
      was assessed in the adult female rats. Quinperole (0,1 mg/kg, i.p.), D2-receptor
      agonist and sulpiride (10,0 mg/kg, i.p.), D2-receptor antagonist were injected
      chronically to adult female rats. Learning of these animals was assessed in
      different models: passive avoidance performance and Morris water maze. Chronic
      quinperole administration to females resulted in the appearance of the passive
      avoidance performance in proestrous and estrous, as distinct from the control
      animals. Also, quinperole improved spatial learning in proestrous and stimulated
      it in estrous in Morris water maze. Chronic sulpiride administration similarly
      impaired non-spatial and spatial learning in females during all phases of ovary
      cycle. The results of the study suggest modulating role of D2-receptors in
      learning/memory processes during ovary cycle in the adult female rats.

PMID- 22629864
TI  - [Surfactant protein D--endogenous regulator of inflammation and immune defense].
AB  - Surfactant protein D (SP-D) is a component of lung surfactant, the representative
      of collagen-like lectines (collectines) family. It plays one of the significant
      roles in innate antibody-independent immune response. Structural features of SP
      D, the possibility of its influence on pathogenetic componentes of inflammatory
      reaction, expression of inflammatory mediators and attainment of necessary
      balance between control of inflammatory reaction intensity and formation of the
      proper response to pathogens allow to consider SP-D as a part of innate immune
      system of the lung and endogenous regulator of inflammatory reactions in the
      organism.

PMID- 22629865
TI  - [Neuroprotective and cardioprotective effects of hypothermic preconditioning].
AB  - The literature data testify the there is an early and delayed hypothermic
      preconditioning of brain. Neuroprotective effect of early hypothermic
      preconditioning is a result of activation of adenosine A1 receptors, KATP
      channels. Ras protein and predetermined by a decrease in the synthesis of NO*.
      The infarct-sparing effect of delayed hypothermic preconditioning of brain is
      depended upon protein synthesis de novo. The presented data demonstrate that
      hypothermic preconditioning prevents cardiomyocyte necrosis in response to
      ischemia-reperfusion, improves pump function of the heart during reperfusion
      period, exerts an antiarrhythmic effect. The hypothermic preconditioning exerts
      more pronounced cardioprotective effect than ischemic preconditioning. The
      protective impact of hypothermic preconditioning is depended upon activation of
      protein kinase C, AMP-activated protein kinase (AMPK) and inhibition of MPT pore.
      The reactive oxygen species are triggers and mediators of hypothermic
      preconditioning of heart.

PMID- 22629866
TI  - Emission modulation of DNA-templated fluorescent silver nanoclusters by divalent
      magnesium ion.
AB  - DNA-templated fluorescent silver nanoclusters (Ag NCs) composed of several or
      tens of atoms are gaining much interest because of their unique properties and
      convenient emission tunability by DNA sequence and length. However, the
      modulation by other factors other than DNA is also dependent on the special DNA
      secondary structure formation such as i-motif or G-quadruplex that is stimulated
      by pH or K+. One main observation considered in this work is emission modulation
      of Ag NCs by divalent Mg2+ during or after the clusters' creation. Tuning the
      emitting intensities and band positions can be realized by Mg2+ addition for the
      examined single-stranded DNA (ss-DNA) templates, which is dependent on the
      addition moment of Mg2+, while only intensity modulation should be achieved for
      the used double-stranded DNA (ds-DNA). Despite of this discrepancy, Mg2+ addition
      always induces a lifetime-varied emission state of Ag NCs. The modulated emission
      still follows the common nature of the previously used DNA sequence- and length
      dependent emitting. Efficient screening the negative charges of DNA backbone upon
      addition of the divalent ion is responsible for the modulation by adaptively
      accommodating the formed Ag NCs. This strategy could be more advantageous over
      the emission modulation by DNA sequence and length because a desired emitting
      could be achieved only by alteration of the electrolyte conditions during or
      after the Ag NCs' creation.

PMID- 22629867
TI  - Biocatalytically induced growth of gold nanoshells: using enzyme reaction for the
      controllable fabrication of nanomaterials.
AB  - In the present work, the enzymatically controlled growth process of gold
      nanoshells (GNSs) in the presence of O2/glucose/glucose oxidase (GOx) and its
      chloroaurate ion electron acceptor is described. The biocatalytically stimulated
      growth process is one of the bio-inspired synthetic procedures directed by
      biological molecules which occur under ambient conditions. It is found that
      hydrogen peroxide (H2O2) could enlarge the gold nanoparticles (GNPs) on the
      surface of GNSs precursor composites, of which the preadsorbed GNPs serve as
      nucleation sites for further gold deposition. Here, GOx is harnessed for its
      unparalled level of catalytic activity and substrate specificity while H2O2 is
      produced as a by-product during the oxidation of D-glucose to gluconic acid by
      GOx. Then the bio-generated H2O2 is used as the reducing agent in the catalytic
      deposition process of GNSs formation. During the procedure, the localized surface
      plasmon resonance peaks range across hundreds of nanometers from visible to near
      infrared region accompanying by the resultant formation of uniform and continuous
      core-shell nanostructures. The corresponding optical, morphological and enzyme
      kinetic properties are all well investigated. The novel protocol offers a new
      perspective for the bio-directed synthesis method in nanotechnology.

PMID- 22629868
TI  - N-alkyl-polyethylenimine stabilized iron oxide nanoparticles as MRI visible
      transfection agents.
AB  - An amphiphilic polymer, alkylated branched polyethylenimine (N-Alkyl-PEI), is
      synthesized and used for stabilization of hydrophobic superparamagnetic iron
      oxide (SPIO) nanocrystals in aqueous phase. Such composite particles are
      monodisperse without aggregation in physiological buffer as verified by dynamic
      light scattering (DLS) and transmission electron microscopy (TEM). The
      nanocomposite system is capable of binding and delivering plasmid DNA for gene
      transfection while maintaining magnetic properties and biocompatibility.
      Transfection of cells showed that N-Alkyl-PEI2k stabilized magnetite
      nanoparticles were most effective in gene transfection comparing to unmodified
      PEI2k and PEI25k agents. Obvious MR signal darkening of transfected cells was
      observed under a clinical 3T MRI scanner. This multifunctional nanocomposite
      system provides a safe and efficient method for gene delivery with non-invasive
      imaging monitoring capability.

PMID- 22629869
TI  - Antimicrobial properties of uncapped silver nanoparticles synthesized by DC arc
      thermal plasma technique.
AB  - We, herein, report the antimicrobial properties of uncapped silver nanoparticles
      for a Gram positive model organism, Bacillus subtilis. Uncapped silver
      nanoparticles have been prepared using less-explored DC arc thermal plasma
      technique by considering its large scale generation capability. It is observed
      that the resultant nanoparticles show size as well as optical property dependent
      antimicrobial effect.

PMID- 22629870
TI  - Investigation of biological property of nanohydroxyapatite materials.
AB  - The biological effects of nanohydroxyapatites and its cell toxicity have been
      studied using the MTT and ALP method, infrared spectrum of absorption and
      electrophoresis method, respectively. The nanohydroxyapatites are prepared and
      made by using sol-gel method, in which the parameters of process and reaction are
      controlled as: pH > 9, Ca/P = 1.67, sintering temperature of 1100 degrees C and
      sintering time 2 hours. Studied results show that nanohydroxyapatites can
      interact with human serum albumin and change its second structure and weight of
      molecules. We find that the nanohydroxyapatites and complex of nanoHAP + nanoCrO2
      can all restrain the proliferation of MG63 cells, but their toxicities are first
      degree or minor, the toxicity of the complex is smaller than that of pure
      nanohydroxyapatites.

PMID- 22629871
TI  - Physical properties of nano-HAs/ZrO2 coating on surface of titanium materials
      used in dental-implants and its biological compatibility.
AB  - A gradient composite coating on the surface of titanium materials, which are used
      in dental implants, is prepared using an electric-chemical method. The physical
      properties of the composite coating and its strength of combining with titanium
      material are studied by the scanning electron microscope, energy dispersive
      spectrum and X-ray diffraction analysis, etc. The results show that the
      nanohydroxyapatite/ZrO2 composite coating is uniformly deposited and formed on
      the surface of titanium materials, its strength of combining with titanium
      surface reaches 16.3 MPa, which is determined by the tensile test. The immersion
      experiment shows that a new matter of carbonate-apatite is distributed uniformly
      on the surface of the composite coating of nanohydroxyapatite/ZrO2. The cell
      experiment of cultivate exhibits that the osteoblasts MG-63 is also grown well on
      the surface of the composite coating. These results indicate that the
      nanohydroxyapatite/ZrO2 composite coating on the surface of titanium materials
      has a good biological activity and compatibility and could be used in the dental
      implants.

PMID- 22629872
TI  - Photodynamic effect of mesoporous material: titanium dioxide whiskers on SMMC
      7721 cells.
AB  - In this report, we have fabricated a novel nanomaterial, titanium dioxide
      whiskers (TiO2Whs), and evaluate its photodynamic characters on Rhodamine B,
      where TiO2Whs exhibit better photocatalytic activity than titanium dioxide
      nanoparticles (TiO2NPs). After testing the biocompatibility, we further
      investigated the effects of TiO2Whs on human hepatocarcinoma cells (SMMC-7721
      cells) under UV illumination from cell level, concentration-dependent effect
      level, time-dependent effect level, and finally genomic apoptosis level. Our
      results showed that TiO2Whs possess more obviously photo-killing effect on cancer
      cells compared with that of TiO2NPs. These studies implied that the novel
      nanomaterial, TiO2Whs, could be utilized as a promising biomedical agent and
      would have enormous potential application in photodynamic therapy for cancer
      treatment in the future.

PMID- 22629873
TI  - Synthesis of silver nanoparticles in poly(vinyl alcohol) matrix in solution and
      thin films through laser irradiation.
AB  - Here we communicate our experimental results on the synthesis of silver
      nanoparticles in solution and thin films using silver nitrate and poly vinyl
      alcohol (PVA) mixture at different concentrations and different laser
      irradiations. Detailed studies were carried out by varying pulse width,
      wavelength, exposure time, and energy of the laser. Formation of nanoparticles
      was confirmed through color change from transparent to yellow. Irradiated
      solutions and thin films at different concentrations showed plasmon peak in the
      absorption spectra. Formation of different sized nanoparticles at different
      energies with peak shift is observed. Transmission electron microscope (TEM)
      results confirmed the formation of nanoparticles with size of the particles
      varying from 2 to 200 nm. Formation of silver nanoparticles with hexagonal and
      different shapes were observed in particular with 355 nm laser irradiation.
      Influence of wavelength, pulse width, exposure time, and energy in the synthesis
      of silver nanoparticles is highlighted. Electron diffraction patten of a single
      nanoparticle in TEM showed polycrystallinity with cubic nature for the silver
      nanoparticles prepared. We also compared the linear and nonlinear absorption
      properties of the freshly prepared nanoparticles with nanoparticles solution left
      in a shelf for a long period of time.

PMID- 22629874
TI  - Photocatalytic degradation of azo dyes using Au:TiO2, gamma-Fe2O3:TiO2 functional
      nanosystems.
AB  - We report photocatalytic degradation studies on Navy Blue HE2R (NB) dye on
      significant details as a representative from the class of azo dyes using
      functional nanosystems specifically designed to allow a strong photocatalytic
      activity. A modified sol-gel route was employed to synthesize Au and gamma-Fe2O3
      modified TiO2 nanoparticles (NPs) at low temperature. The attachment strategy is
      better because it allows clear surface of TiO2 to remain open for photo
      catalysis. X-ray diffraction, Raman and UV-VIS spectroscopy studies showed the
      presence of gold and iron oxide phases along-with the anatase TiO2 phase. TEM
      studies showed TiO2 nanocomposite particles of size approximately 10-12 nm. A
      detailed investigation on heterogeneous photocatalytic performance for Navy Blue
      HE2R dye was done using the as-synthesized catalysts Au:TiO2 and gamma-Fe2O3:TiO2
      in aqueous suspension under 8 W low-pressure mercury vapour lamp irradiation.
      Also, the photocatalytic degradation of Amranth and Orange G azo dyes were
      studied. The surface modified TiO2 NPs showed significantly improved
      photocatalytic activity as compared to pure TiO2. Exposure of the dye to the UV
      light in the presence of pure and gold NPs attached TiO2 catalysts caused dye
      degradation of about approximately 20% and approximately 80%, respectively, in
      the first couple of hours. In the presence of gamma-Fe2O3 NPs attached TiO2, a
      remarkable approximately 95% degradation of the azo dye was observed only in the
      first 15 min of UV exposure. The process parameters for the optimum catalytic
      activity are established which lead to a complete decoloration and substantial
      dye degradation, supported by the values of the Chemical Oxygen Demand (COD)
      approximately 93% and Total Organic Carbon (TOC) approximately 65% of the treated
      dye solution after 5 hours on the employment of the UV/Au:TiO2/H2O2
      photocatalytic process.

PMID- 22629875
TI  - Preparation and characterization of ZnO-graphene composite photocatalyst.
AB  - ZnO is one of potential semiconductor materials in photocatalytic field, and
      appears to be a suitable alternative to TiO2, due to its photochemical properties
      and photodegradation mechanism similar to TiO2. Graphene is a single 2D carbon
      sheet with large specific surface and excellent electric conductivity. The
      combination of ZnO and graphene could extremely improve the photocatalytic
      activity of ZnO. Herein we prepared ZnO-graphene nanocomposite photocatalyst
      using graphite and ZnO by a facile one-step hydrothermal method. During the
      hydrothermal reactions, both of the reduction of graphene oxide and loading of
      ZnO were occurred simultaneously and the desired product was obtained. The as
      prepared ZnO-graphene photocatalyst exhibited extraordinaire photocatalytic
      properties. Results of photocatalytic degradation of methyl orange show that the
      photocatalysis efficiency of the composite was significant enhanced, compared to
      pure ZnO. This work could provide new avenue for the fabrication of ZnO-carbon
      based composites, facilitating their application in pollutions degradation
      issues.

PMID- 22629876
TI  - Metallicity and ferromagnetism in nanosystem of charge ordered Nd0.5Sr0.5MnO3.
AB  - The fascinating phenomenon of destabilization of charge/orbital order in
      Nd0.5Sr0.5MnO3 with the reduction of grain size is critically investigated. Based
      on our magnetic and transport experiments followed by a theoretical analysis, we
      analyze various possible mechanisms and try to delineate a universal scenario
      behind this phenomenon. We revisit this issue carefully and discuss various
      evidences from experiments in nano and bulk manganites on the absence of
      correlation between size reduction and pressure effects on manganites. We propose
      a phenomenological model based on enhanced surface disorder to explain the
      appearance of weak ferromagnetism and metallicity in nanosize Nd0.5Sr0.5MnO3
      system. All evidence seems to suggest that the transport is mediated through the
      surface via enhanced density of states in the nanometric grains. We provide
      theoretical support for this by performing an ab-initio electronic structure
      calculation as well as from a recent numerical simulation and argue that the
      mechanism is likely to be general in all nanosize charge ordered manganites.

PMID- 22629877
TI  - Effect of annealing temperature on the structural and magnetic properties of Co
      doped TiO2 nanoparticles via complex-polymer sol-gel method.
AB  - Co-doped TiO2 nanoparticles were synthesized via non hydrous complex-polymer sol
      gel method. A series of Co(x):Ti1-x O2 samples with x = 0.01, 0.03, 0.05, 0.08
      and 0.10, were prepared and subsequently annealed at 400 degrees, 600 degrees and
      800 degrees C. Structural and magnetic properties of Co(x):Ti1-x O2 have been
      studied by means of X-ray diffraction and DC magnetometry. All samples annealed
      at 400 degrees C show a paramagnetic behavior with an average grain size of 11
      nm. With increasing annealing temperatures a complete crystallization is seen
      with growth of the cluster size up to 31 nm with clear evidence of a presence of
      CoTiO3. For all concentrations and annealing conditions no sign of a metallic
      phase, even at x = 0.10, is seen.

PMID- 22629878
TI  - A critical appraisal of the nanoindentation creep 'nose' effect in Ni thin films.
AB  - The creep behaviour of polycrystal Ni thin films under the same maximum load
      (Pmax = 8000 microN) and different unloading periods (ranging from 1 to 250 s)
      has been investigated at room temperature using nanoindentation tests. A 'nose'
      has been observed in the unloading segment of the load-penetration depth curve
      when the holding time at peak load is short and/or the unloading rate is small,
      and when the peak load is sufficient high. When a 'nose' presents, the apparent
      unloading stiffness Su, defined as dP/dh, is negative, and the reduced modulus
      can no longer be calculated from the Oliver-Pharr method. Taking such
      uncertainties into account, a critical appraisal is proposed for ranking creep
      propensities exhibited during nanoindentation under specified conditions.

PMID- 22629879
TI  - High hardness BaCb-(BxOy/BN) composites with 3D mesh-like fine grain-boundary
      structure by reactive spark plasma sintering.
AB  - Boron carbide B4C powders were subject to reactive spark plasma sintering (also
      known as field assisted sintering, pulsed current sintering or plasma assisted
      sintering) under nitrogen atmosphere. For an optimum hexagonal BN (h-BN) content
      estimated from X-ray diffraction measurements at approximately 0.4 wt%, the as
      prepared BaCb-(BxOy/BN) ceramic shows values of Berkovich and Vickers hardness of
      56.7 +/- 3.1 GPa and 39.3 +/- 7.6 GPa, respectively. These values are higher than
      for the vacuum SPS processed B4C pristine sample and the h-BN -mechanically-added
      samples. XRD and electronic microscopy data suggest that in the samples produced
      by reactive SPS in N2 atmosphere, and containing an estimated amount of 0.3-1.5%
      h-BN, the crystallite size of the boron carbide grains is decreasing with the
      increasing amount of N2, while for the newly formed lamellar h-BN the crystallite
      size is almost constant (approximately 30-50 nm). BN is located at the grain
      boundaries between the boron carbide grains and it is wrapped and intercalated by
      a thin layer of boron oxide. BxOy/BN forms a fine and continuous 3D mesh-like
      structure that is a possible reason for good mechanical properties.

PMID- 22629880
TI  - Nano-engineered optimal templates for surface-plasmon enhanced Raman scattering.
AB  - We investigated the critical conditions to realize reliable and nano-engineered
      templates for surface-plasmon enhanced Raman scattering (SERS). Ultra-sensitive
      SERSs of thymine oligonucleotides were successfully realized on the template of
      Au nanoparticle arrays which were prepared by the combination of electron-beam
      lithography and post-chemical modification techniques. Drastic enhancement of
      Raman signal from the thymine oligonucleotides was only observed on the optimized
      templates, where the tuning of the plasmon resonance condition and the formation
      of the hot spots were both critical. Our results suggest that the artificial
      generation of reproducible and controlled hot spots can be achieved by our
      approach.

PMID- 22629881
TI  - Temperature dependant characteristics of zinc oxide nanorods based heterojunction
      diode.
AB  - Temperature-dependant characteristics of heterojunction diode made by n-ZnO
      nanorods grown on p-silicon substrates has been characterized and demonstrated in
      this paper. ZnO nanorods were grown onto the silicon substrate via simple thermal
      evaporation process by using metallic zinc powder in the presence of oxygen at
      approximately 550 degrees C without the use of any metal catalysts or additives.
      The as-grown ZnO nanorods were characterized in terms of their structural and
      optical properties. The detailed structural studies by XRD, TEM, HRTEM and SAED
      revealed that the grown nanorods are well-crystalline with the wurtzite hexagonal
      phase and preferentially grown along the [0001] direction. The as-grown n-ZnO
      nanorods grown on p-Si substrate were used to fabricate p-n heterojunction diode.
      The fabricated p-n junction diode attained almost similar turn-on voltage of
      approximately 0.6 V. The values of turn-on voltage and least current are same
      with the variations of temperature (i.e., 27 degrees C, 70 degrees C and 130
      degrees C).

PMID- 22629882
TI  - A simple and effective method to form metallic nanoparticles onto composites made
      up of organic polymers and layered inorganic ion exchangers as fillers.
AB  - A new easy method for the preparation of polymeric nanocomposites supporting
      metal nanoparticles is presented. The method concerns the use of a layered
      inorganic ion exchanger converted in the proper metallic form and exfoliated to
      act as filler of organic polymers with twofold aim of obtaining a composite (or
      nanocomposite) and to have metal ions that can be suitably reduced with a proper
      reducing agent to form metal nanoparticles. This strategy has been applied to the
      system polyvinylidene fluoride (PVDF) filled with layered a-zirconium phosphate
      in copper form. Several physical techniques (X-ray powder diffraction, atomic
      force microscopy, high resolution transmission electron microscopy) have been
      used to characterize the Cu-nanoparticles, whose dimensions range from 5 to 200
      nm for those placed inside or on the surface of the polymeric matrix
      respectively, depending on the dispersion degree of the inorganic filler. The
      method is simple and can be used for different polymeric matrices and/or metal
      ions in order to produce metal/polymer systems with promising technological
      application.

PMID- 22629883
TI  - Fabrication of epoxy composites with large-pore sized mesoporous silica and
      investigation of their thermal expansion.
AB  - We fabricate epoxy composites with low thermal expansion by using mesoporous
      silica particles with a large pore diameter (around 10 nm) as inorganic fillers.
      From a simple calculation, almost all the mesopores are estimated to be
      completely filled with the epoxy polymer. The coefficient of linear thermal
      expansion (CTE) values of the obtained epoxy composites proportionally decrease
      with the increase of the mesoporous silica content.

PMID- 22629884
TI  - Lanthanide metals adsorbed in an open-cage Fullerene: first-principles
      calculations.
AB  - In this paper, the properties of a 12-membered-ring open-cage fullerene, which
      encapsulate La, Ce, Pr, Nd, Pm, Sm, Eu or Gd, as a guest atom, were calculated
      using first-principle calculations. Calculations show that La etc. lanthanide
      metal atoms can be stably adsorbed on the openings of the fullerenes. The average
      adsorption energy is about -3.65 eV in which Pr and Nd have relatively large
      adsorption energy with -4.75 eV and -4.63 eV, respectively. The Gd is stably
      adsorbed on the side wall near bottom of the fullerene with adsorption energy of 
      3.05 eV. The PDOS of adsorbed lanthanides were analyzed, respectively. Magnetic
      property of adsorbed lanthanides was also discussed. From the calculation, it is
      proved that most of the adsorbed lanthanides keep good magnetic property.
      Finally, vertical ionization potential and vertical electron affinity of the
      complex compounds were researched. The results show that the possibility of
      donating electrons of the 12-membered-ring open-cage fullerene is significantly
      affected by the endohedral lanthanide metals. From our calculations, it is
      believed that the complex compounds could be promising candidates for medicine
      carrier.

PMID- 22629885
TI  - A thermo dynamical model for the shape and size effect on melting of boron
      carbide nanoparticles.
AB  - The size and shape dependence of the melting temperature of Boron Carbide (B4C)
      nanoparticles has been investigated with a numerical thermo dynamical approach.
      The problem considered in this paper is the inward melting of nanoparticles with
      spherical and cylindrical geometry. The cylindrical Boron Carbide (B4C)
      nanoparticles, whose melting point has been reported to decrease with decreasing
      particle radius, become larger than spherical shaped nanoparticle. Comparative
      investigation of the size dependence of the melting temperature with respect to
      the two shapes is also been done. The melting temperature obtained in the present
      study is approximately a dealing function of radius, in a good agreement with
      prediction of thermo dynamical model.

PMID- 22629886
TI  - Breakdown of ballistic conduction in Single-atom-width gold wires.
AB  - Single-atom-width gold wires were produced by stretching gold nanocontacts using
      piezomanipulation inside a high-resolution transmission electron microscope. The
      structure of the wires was observed in situ with simultaneous conductance
      measurements. The conductance of the wires depended on the length; the
      conductance decreased from 1G0 to 0.1G0 (G0 = 2e2/h, where e is the charge of an
      electron and h is Planck's constant) as the length increased from 1 atom to 7
      atoms. The results show that ballistic conduction breaks down in the wires.

PMID- 22629887
TI  - Interface characterization of epitaxial Fe/MgO/Fe magnetic tunnel junctions.
AB  - Following predictions by first-principles theory of a huge tunnel
      magnetoresistance (TMR) effect in epitaxial Fe/MgO/Fe magnetic tunnel junctions
      (MTJs), measured magnetoresistance (MR) ratios of about 200% at room temperature
      (RT) have been reported in MgO-based epitaxial MTJs. Recently, a MR ratio of
      about 600% has been reported at RT in MgO-based MTJs prepared by magnetron
      sputtering, using amorphous CoFeB as the ferromagnetic electrode. These MTJs show
      great potential for application in spintronic devices. Fully epitaxial MTJs are
      excellent model systems that enhance our understanding of the spin-dependent
      tunneling process as the interface is well defined and can be fully
      characterized. Both theoretical calculations and experimental results clearly
      indicate that the interfacial structure plays a crucial role in the coherent
      tunneling across a single crystal MgO barrier, especially in epitaxial MgO-based
      MTJs grown by molecular beam epitaxy (MBE). Surface X-ray diffraction, Auger
      electron spectroscopy, X-ray absorption spectra, and X-ray magnetic circular
      dichroism techniques have been reported previously for interface
      characterization. However, no consistent viewpoint has been reached on the
      interfacial structures (such as FeO layer formation at the bottom Fe/MgO
      interface), and it is still an open issue. In this article, our recent studies on
      the interface characterization of MgO-based epitaxial MTJs by X-ray photoelectron
      spectroscopy, high resolution transmission electron microscopy, and spin
      dependent tunneling spectroscopy, will be presented.

PMID- 22629888
TI  - Thermochemotherapy mediated by novel solar-planet structured magnetic
      nanocomposites for glioma treatment.
AB  - Cancer comprehensive treatment has been fully recognized as it can provide an
      effective multimodality approach for fighting cancers. This work evaluates the
      effects of a kind of novel solar-planet structured magnetic nanocomposites (MNCs)
      for magnetic thermochemotherapy. Amino silane coated magnetic nanoparticles
      (MNPs) as agent of magnetic mediated hyperthermia (MMH) for cancer treatment were
      prepared by the chemical precipitation method. Docetaxel (an anticancer drug)
      loaded polymeric nanoparticles (DNPs) composed of carboxylic-terminated poly (D,L
      lactic-co-glycolic acid) (PLGA) with Vitamin E TPGS as emulsifier for sustained
      drug release were prepared by a modified solvent extraction/evaporation
      technique. Furthermore, the MNPs modified with amino groups could be covalently
      attached to the surface of carboxylic terminated DNPs to form the so-called solar
      planet structured MNCs by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)
      and N-hydroxysuccinimide (NHS) crosslinking. The prepared solar-planet structure
      has been confirmed by fluorescent observation. Inductive heating property of the
      nanocomposite was evaluation by monitoring the temperature increase of the MNCs
      suspension under alternative magnetic field (AMF). Drug encapsulation efficacy
      and drug release of the magnetic nanocomposite were conducted by high performance
      liquid chromatography (HPLC). In vitro evaluation of the novel nanocomposite as
      mediator for thermochemotherapy was conducted on the U251 human glioma cells and
      the synergistic effect between MMH and docetaxel chemotherapy was confirmed. All
      the observation supports that solar-planet structured MNC is a novel and
      effective mediator for magnetic thermochemotherapy. The MNCs can realize cancer
      comprehensive treatment thus has great potential in clinical application.

PMID- 22629889
TI  - Structure and magnetic property of the FePt/CrPt bilayer.
AB  - In this work we have studied the growth sequence of L10-CrPt antiferromagnetic
      layer effects on the microstructure and magnetic properties of the FePt/CrPt
      bilayer. The microstructure characteristics were investigated by means of X-ray
      diffraction and the magnetic properties were measured at room temperature by
      using a vibrating sample magnetometer. Structural analysis showed that the low
      temperature ordering and the in-plane orientation of the FePt layer with the CrPt
      underlayer were promoted due to lattice mismatch optimized after annealing at 350
      degrees. Meanwhile, magnetic analysis also revealed that the FePt/CrPt bilayer
      had much larger exchange bias (H(E)) and higher coercivity (Hc) when the CrPt
      layer was as the underlayer after annealing at 350 degrees.

PMID- 22629890
TI  - Magnetization reversal and anisotropy with chains of superparamagnetic Ni
      nanoparticles.
AB  - Chains of superparamagnetic (SPM) Ni nanoparticles of 20 and 33 nm in diameter
      are synthesized by a facile, template-free, wet chemical method in magnetic
      field. The blocking temperature for the sample of 20 nm appears at T(B)
      approximately 255 K, above which the sample exhibits SPM behaviors by a M(H)
      measurement. At T < T(B), the temperature dependent coercivity, Hc(T), is beyond
      the description by the simple two-well model proposed by Neel and Brown in the
      early day. In contrast, for the Ni nanochains of diameter larger than the
      coherence length, Lcoh approximately 25 nm, the magnetization reversal properties
      are well described by this model. The magnetization reversal behavior of the SPM
      Ni nanochains with the diameter much smaller than the coherence length is one of
      the interesting points to study. Possible transition from the localized
      magnetization reversal mode in the high temperature end to the coherently
      rotational mode at low temperature is discussed.

PMID- 22629891
TI  - Effect of crystal grain dimension on the magnetic properties and magnetocaloric
      effects in DyCuAl compound.
AB  - The influence of crystal grain dimension (approximately 38 nm and approximately
      90 nm) on magnetic properties and magnetocaloric effects has been investigated
      for DyCuAl compound. The reduction of crystal grain dimension leads to the
      decrease of the Curie temperature (from 27 K to 24 K) and the evident enhancement
      of magnetic anisotropy. The peak values of magnetic entropy change under a field
      change of 0-5 T are 14.9 J kg(-1) K(-1) and 20.4 J kg(-1) K(-1) for DyCuAl
      compounds (approximately 38 nm and approximately 90 nm), respectively. A large
      refrigerant capacity is also produced in DyCuAl compounds (423 J kg(-1) and 379 J
      kg(-1) for the same field change, respectively). Large magnetic entropy changes
      and refrigerant capacities jointly make them attractive candidates for low
      temperature magnetic refrigerant.

PMID- 22629892
TI  - Study of magnetization reversal by minor loops in IrMn/CoFe exchange-biased
      bilayers.
AB  - We report a detailed investigation of the magnetization reversal by minor loops
      in Co75Fe25 (t) single layer and Ir22Mn78(10 nm)/CoFe(t) exchange-biased bilayers
      with different CoFe thicknesses. With increasing CoFe layer thickness in
      IrMn/CoFe bilayers, the magnetization reversal process shows a transition from
      the coherent rotation to the domain-wall motion, which is attributed to the
      competition among the antiferromagnetic domain wall energy, ferromagnetic domain
      wall energy, and the interface coupling between antiferromagnetic and
      ferromagnetic layers.

PMID- 22629893
TI  - Annealing effect on the structure and electronic transport properties in
      La5/8Ca3/8MnO3/ErMnO3 multilayer thin films.
AB  - Ferromagnetic La5/8Ca3/8MnO3 (LCMO) and Ferroelectric ErMnO3 (EMO) multilayer
      thin films with sandwich structure (LCMO/EMO/LCMO) were grown on
      (LaAlO3)0.3(Sr2AlTaO6)0.7 (001) [LSAT (001)] substrates by pulsed laser
      deposition (PLD) method. For these films, the structural characterization was
      carried out by X-ray diffraction (XRD), and the temperature-dependence
      resistivity (p-T) showing the metal-insulator transition (Tp) also was measured.
      In the multilayer thin films the LCMO (002) peak move to lower Bragg angles after
      annealing at 900 degrees C for 30 hours under 1atm Oxygen pressure, and this
      condition is much different from the LCMO single layer films where the (002) peak
      moves to higher Bragg angle after annealing due to the lattice mismatch between
      the LCMO layer and the substrate. By increasing the thickness of LCMO, the
      multilayer samples show two MR peaks in a wide temperature range during the
      process of M-l transition. This phenomenon is attributed to a new
      (La5/8Ca3/8)xEr(1-x)MnO3 layer produced by the solubility between LCMO and EMO
      layers after high-temperature annealing. In this paper, we provide some evidence
      of dissolution between LCMO and EMO layers, and discuss the influence on
      structure and electronic transport properties in the composite thin films by
      annealing.

PMID- 22629894
TI  - Effects of the inhomogenous co doping on the magnetoresistance of Zn1-xCo(x)O
      epitaxial films.
AB  - A series of Zn1-xCo(x)O epitaxial films around 100 nm with nominal Co
      concentration from 5% to 15% was prepared by ultra high vacuum (UHV) magnetron
      reactive sputtering. The optical, magnetic and magneto-transport properties of
      this series of Zn1-xCo(x)O epitaxial films were investigated, respectively.
      Resonant Raman spectra indicate the high structural and crystalline quality of
      these Zn1-xCo(x)O (5 < or = x < or = 15%) films, and confirm a consistent
      correlation between the substituting Co ions content with the Co doping
      concentration as well. Paramagnetism, superparamagnetism and ferromagnetism with
      altered Curie temperature from low temperatures to above room temperatures have
      been observed in these films by SQUID magnetometry. The broad blocking
      temperature range indicates the presence of inhomogenous distribution of the
      magnetic nano-clusters in the superparamagnetic films. However, the magneto
      transport behaviors do not strongly respond to the change of the magnetic
      properties from paramagnetism to ferromagnetism of these Zn1-xCo(x)O films. The
      lack of efficient coupling between the inhomogenous magnetic nanoclusters and the
      carrier system in ferromagnetic Zn1-xCo(x)O films highlights the absence of the
      intrinsic magnetic origins in high structural quality Zn1-xCo(x)O (5 < or = x <
      or = 15%) epitaxial films. On the other hand, the competition between the spin
      alignments and the inhomogenous local disorder effect by magnetic ions is
      suggested to be responsible for the carrier properties and the oberseved
      magnetoresistance in these Co doping Zn1-xCo(x)O (5 < or = x < or = 15%)
      epitaxial films.

PMID- 22629895
TI  - Oxygen implanted Ni/NiO exchange bias system: fabrication, structure and magnetic
      property.
AB  - Ion implantation is used to build a nanometer scale anti-ferromagnetic (AFM)
      cluster embedded exchange bias (EB) system. Ni film with a thickness of 100 nm is
      deposited on the Si (100) substrate using magnetron sputtering, 140 keV O+ is
      chosen to implant into the Ni film to form NiO AFM clusters, of which the size is
      estimated by X-ray diffraction based on synchrotron radiation (SR-XRD). By
      measuring hysteresis loop after field-cooling, significant shifts of loop along
      the applied field are observed. By increasing the implantation dose up to 3 x
      10(17)/cm2 and annealing samples in N2 atmosphere, we discuss the origin of EB
      effect observed and the size confinement effect which lowers down the Neel
      temperature (T(N)) of NiO cluster to below room temperature.

PMID- 22629896
TI  - Spin-polarized current driven vortex-pair Switching in a magnetic ellipse.
AB  - Micromagnetic simulations are performed to study the mechanism of vortex core
      reversal in a Permalloy elliptical element that contains two vortices with
      opposite polarities. A short current pulse is applied in the film plane along the
      short axis of the ellipse. The trajectories of the two vortex cores move either
      clockwise or anticlockwise, depending on the core polarization. Their reversal
      mechanisms of the two cores are the same through a creation-annihilation process
      of vortex-antivortex pair. By analyzing the partial energies of the sample we
      find that the core reversal occurs once the maximum local energy density reaches
      the threshold value (e.g., approximately 3.0 x 10(6) J/m3 for Permalloy).
      Interestingly, this energy threshold is a universal constant, irrespective of the
      applied current strength, vortex polarity and the sample size.

PMID- 22629897
TI  - Magneto-optical stokes polarimetry and nanostructured magnetic materials.
AB  - Stokes parameters fully characterize the polarization state of light in an
      experimentally accessible manner. Photoelastic modulator (PEM) based Stokes
      polarimetry offers a very high sensitivity which is particularly suitable for the
      investigation of the magneto-optical properties of nanostructured magnetic
      materials. In this paper, we shall describe a robust methodology recently
      developed by us that utilizes a dual PEM setup. As an example of its application,
      we report on the magneto-optical characteristics of focused Ga ion beam patterned
      Fe films. We have investigated Ga ion irradiation of single-layer polycrystalline
      Fe films deposited on Si3N4 substrates, which allows us to study the effects of
      ion implantation with minimum added complications. Complemented by structural and
      other characterization techniques, the absolute measurement of magneto-optical
      effects through the determination of Stokes parameters has enabled us to
      effectively separate the various contributions from film thinning due to
      sputtering, structural modifications and compositional changes caused by Ga
      incorporation. A comparison is also made between the magneto-optical behavior of
      patterned thin films and that of anodic aluminum oxide embedded magnetic nanowire
      arrays.

PMID- 22629898
TI  - Crystallization of cobalt amorphous alloys under field annealing.
AB  - Crystallization of Co-rich amorphous ribbons annealed under a 10 Oe external
      magnetic field at the early 30 minutes from their glassy status to supercooled
      liquid status is investigated by high-resolution transmission microscope (HR
      TEM), Selected Area Fourier Transform (SA-FT), X-ray diffraction (XRD) and
      differential scanning calorimetry (DSC). Results indicate that the short-rang
      ordering feature can be refined very well in specimen annealed under temperatures
      about 87.4 degrees C below their glass transition (Tg), showing refined salt
      pepper morphologies with a mean length changing from 1.2 +/- 0.8 nm to 0.8 +/-
      0.2 nm and a mean width shifting from 0.5 +/- 0.2 nm to 0.3 +/- 0.1 nm. When the
      amorphous ribbons are field-annealed at temperature near to Tg (i.e., 450 degrees
      C), ultra-fine nanocrystalline structures can be formed on the top surface of
      ribbons with size of 3.5 +/- 0.5 nm and inter-grain spacing of about 0.4 +/- 0.2
      nm even though the inner parts of the ribbons are still in amorphous phases. The
      nanocrystalline areas are featured by the formation of doped hcp cobalt phase
      orientated along the c-axis, with the inter-plane spacing ranging from 4 A to 6
      A. When the annealing temperature is above Tg, the grain sizes are increased
      dramatically with multi-phased nanocrystals precipitating from the amorphous
      substrate, and finally reaching almost complete crystallization at 600 degrees C,
      causing greatly coarsening of the nanocrystal structures.

PMID- 22629899
TI  - Crystallographic structure and magnetic properties in L1(0) FePt thin films
      deposited at different temperature.
AB  - The crystallographic structure and magnetic properties of L1(0) FePt thin films
      deposited at different substrate temperature were investigated systematically in
      present paper. The ordered L1(0) FePt thin film was developed when substrate
      temperature is higher than 300 degrees C. The ordering parameter S, the degree of
      tetragonality c/a, and the epitaxial quality of the films, increase with
      increasing substrate temperature. The squareness and coercivity in the direction
      perpendicular to the film increase as the substrate temperature is increased and
      the perpendicular anisotropy is developed when the substrate temperature is
      higher than 300 degrees C. The magnetic anisotropy Ku increases with increasing
      substrate temperature and it might be concluded that the magnetic anisotropy of
      ordered L1(0) FePt thin films mainly stems from the magnetocrystalline origin and
      also possibly due to pair ordering mechanism.

PMID- 22629900
TI  - Tunable magnetic properties by interfacial manipulation of L1(0)-FePt
      perpendicular ultrathin film with island-like structures.
AB  - Based on interfacial manipulation of the MgO single crystal substrate and non
      magnetic AIN compound, a L1(0)-FePt perpendicular ultrathin film with the
      structure of MgO/FePt-AIN/Ta was designed, prepared, and investigated. The film
      is comprised of L1(0)-FePt "magnetic islands," which exhibits a perpendicular
      magnetic anisotropy (PMA), tunable coercivity (Hc), and interparticle exchange
      coupling (IEC). The MgO substrate promotes PMA of the film because of interfacial
      control of the FePt lattice orientation. The AIN compound is doped to increase
      the difference of surface energy between FePt layer and MgO substrate and to
      suppress the growth of FePt grains, which takes control of island growth mode of
      FePt atoms. The AIN compound also acts as isolator of L1(0)-FePt islands to pin
      the sites of FePt domains, resulting in the tunability of Hc and IEC of the
      films.

PMID- 22629901
TI  - An investigation of nickel cobalt oxide nanorings using transmission electron,
      scanning electron and helium ion microscopy.
AB  - Nickel cobalt oxide alloy nanorings have been synthesized using a wet chemistry
      method. Standard characterization techniques such as transmission electron
      microscopy (TEM) and scanning electron microscopy (SEM) have been used to
      characterize the nanorings. We, however, also examined the nanostructures in the
      helium ion microscope (HIM) and employed backscattered ion spectroscopy to
      determine thickness and composition of the nanostructure. The HIM provides
      complementary information of the nanostructures and the viability of using it as
      a tool for magnetic nanoparticle characterization was demonstrated by comparing
      the results from all three microscopes.

PMID- 22629902
TI  - Effects of Cu underlayer on the growth and magnetic properties of FePt thin films
      on MgO (001) substrate.
AB  - During ordering process of face centered tegragonal (fct) L1(0) phase of the FePt
      alloy, there exist three growth variants of axes (001) from original disordered
      fcc structured phase. When FePt film was directly deposited on the MgO (001)
      substrate, the variant perpendicular to the film plane grew, resulting in a low
      out-of-plane coercivity of 1.3 kOe. By using Cu underlayer, two variants lying in
      the film plane got same chance to grow, which caused an in-plane perpendicular
      alignment of the tetragonal axes of FePt L1(0) phases. The crystallographic
      relationship between Cu and FePt layers is Cu (100)<100>//fct FePt (100)<100>. A
      high in-plane coercivity of 4.6 kOe was obtained due to the high density of micro
      defects (mcro-twins, anti-phase boundaries, etc.) in the film plane. This work
      demonstrated a way of selecting the growth variants of ordering process to adjust
      the magnetic properties of the ordered FePt thin films.

PMID- 22629903
TI  - A magnetic and magneto-optical investigation of Co-Pt alloy nanowire arrays.
AB  - We have investigated the magneto-optical properties of highly ordered Co-Pt alloy
      nanowire arrays embedded in anodic aluminum oxide templates. The magnetic field
      dependent Stokes parameters, Faraday rotation angle and ellipticity were
      investigated by an in-house magneto-optical measurement system. The extracted
      hysteresis loops are broadly consistent with magnetic hysteresis loops obtained
      from the vibrating sample magnetometer. The maximum Faraday rotation angle and
      ellipticity of these samples were examined as a function of nanowire composition.
      With an increase of platinum content from 9 at.% to 86 at.% in the as-deposited
      nanowire arrays, the maximum Faraday rotation angle per length decreases linearly
      from 1.39 x 10(3) degrees/cm to 1.58 x 10(2) degrees/cm. The maximum ellipticity
      shows a similar behavior with the composition. These linear relationships suggest
      a dilution model for the magnetic moment in the alloy nanowires. Our results
      indicate that magneto-optical measurements comprise an effective and sensitive
      method for monitoring the behavior of AAO-based magnetic nanowire arrays.

PMID- 22629904
TI  - Large improvement of coercivity in Sm-(Co,Cu)/Fe films by Cu addition.
AB  - The magnetic properties and microstructure of Sm-(Co,Cu)/Fe films were
      investigated systematically. The addition of Cu is helpful for keeping a better
      multilayer structure due to the reduction of the crystallization temperature of
      the hard phase. With lowering the temperature, the coercivity of the Sm
      (Co,Cu)/Fe films increases rapidly with a linear relationship. The Cu addition
      significantly improves the coercivities of the Sm-(Co,Cu)/Fe multilayer films,
      especially at the low temperatures. Adding the Cu as well as lowering the
      temperature cause a large inhomogeneity in the hard phase, and therefore a high
      pinning coercivity.

PMID- 22629905
TI  - Synthesis of Fe-group metal oxide nanostructures by thermal oxidation and their
      magnetic properties.
AB  - In this paper, we review the preparation of Fe-group metal oxide nanostructures
      by the thermal oxidation method developed in our lab. By this method, we have
      prepared several kinds of nanostructures, including nanowires and nanoleaves. The
      magnetic properties of these nanostructures have also been studied. By carefully
      controlling the reacting time, temperature, and humidity, we have prepared alpha
      Fe2O3, gamma-Fe2O3, Fe3O4, and Co3O4 nanowires and alpha-Fe2O3 nanoleaves by
      heating the substrates in proper atmosphere. The alpha-Fe2O3 and Co3O4 nanowires
      are produced by directly oxygenating pure metal at 550 to approximately 650
      degrees C and 480-520 degrees C, separately. The gamma-Fe2O3 and Fe3O4 nanowires
      are produced by reducing as-prepared alpha-Fe2O3 nanowires in a mixture of N2 and
      H2. The nanowires are about 10-20 microm, with diameter of about 20 to
      approximately 100 nm. Most of the nanowire arrays are grown vertically from the
      surface of the substrate at a high surface density (10(8)-10(9) cm(-2)). Compared
      with the nanowires prepared by hydrothermal process and template method, Most of
      our nanowires are structurally uniform and single crystallites. The magnetic
      properties of these nanostructures are also studied, and demonstrate some novel
      properties.

PMID- 22629906
TI  - Synthesis and microwave absorption properties of magnetite nanoparticles.
AB  - Nanoparticles of Fe3O4 with various sizes were synthesized from FeCl3 x 6H2O,
      FeCl2 x 4H2O and NaOH by coprecipitation process. The crystal structure,
      morphology, particle size and magnetic property of the products were
      characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM)
      and vibrating sample magnetometer (VSM). It was found that the molar ratio of
      ferrous to ferric played an important role in the formation of Fe3O4
      nanoparticles. The particle mean diameter swelled from approximately 10 to
      approximately 20 nm with the molar ratio range from 1:2 to 6:1. The saturation
      magnetization and the coercivity increased correspondingly. The complex
      permittivity epsilon(r) and permeability mu(r) of the Fe3O4 mixture with paraffin
      were measured using vector network analysis. Values of epsilon(r), and mu(r) were
      used to determine the reflection loss at various sample thicknesses, based on a
      model of microwave absorbing layer backed by a metal plate. The minimal
      reflection loss or the dip shifts to a lower frequency region with increasing
      thickness. When the thickness is 5 mm, the minimal reflection loss of Fe3O4
      synthesized with the molar ratio of 6:1 and paraffin wax composites reaches -35.1
      dB at 5.2 GHz and -30.2 dB at 17.6 GHz, respectively. The minimal reflection loss
      is attributed to the thickness of the absorber approximates an odd number
      multiple of a quarter of the propagation wavelength.

PMID- 22629907
TI  - The impact of structural parameters on the electrical characteristics of silicon
      nano wire transistor based on non equilibrium Green's function.
AB  - In this paper we have used a fully ballistic quantum mechanical transport
      approach to analyse electrical characteristics of rectangular silicon nanowire
      field effect transistor in 7 nm gate length. We have investigated the impact of
      structural parameters of Gate all around Silicon nano wire transistor (GAA-SNWT)
      on its electrical characteristics in subthreshold regime. In particular we have
      shown the effect of increasing the Source/Drain and channel length (L(S), L(D)
      and L(Ch)) on short channel effects as well as change in body thickness and
      independent back gate voltage. We also investigate the effect of increasing the
      gate underlap on the electrical characteristics and on the switching speed of
      device. We show that if the Lun is increased the gate capacitance and DIBL will
      reduce while the I(ON)/I(OFF) ratio is increased.

PMID- 22629908
TI  - Study on the resin temperature developments during UV imprinting process.
AB  - During the imprinting process, the temperature of the UV resin increases as the
      phase of the resin changes from fluid into solid. During UV curing, some amount
      of heat is released from inside the resin and transferred into contacting
      materials. The heat flow is measured with photo-DSC, and other related thermal
      and mechanical properties of the resin. With the measured material properties,
      the temperature developments both inside of the resin layer and along the
      interfaces of the contacting materials are computed. During the UV exposure
      period, the thermal deformation of the mold, which directly influences the
      pattern distortion are investigated. Under this condition, the developments of
      strain and temperature inside the mold structure including the UV resin of 3-D
      shape are computed with the transient time scale during UV curing according to
      the thickness of resin layer. These computational results are expected to provide
      useful information for better designs of the imprinting mold and the process
      condition.

PMID- 22629909
TI  - Fabrication of nano-LaCrO3 receptor by polymeric precursor method and its
      impedancemetric NOx sensing properties.
AB  - LaCrO3 was prepared by using the polymeric precursor method for use as a receptor
      material and its NOx sensing characteristics were investigated. Nano-LaCrO3
      powders were synthesized at the optimum compositions of the mole ratio of [La-,
      Cr-source]:[EG]:[AcAc] = [a, a]:[160 a]:[8 a] with 1 wt% polyvinylpyrrolidone
      (PVP) using ethylene glycol (EG) as a solvent, acetyl acetone (AcAc) as a
      chelating agent, and PVP as a polymer additive. The thermal decomposition
      behavior, crystal structure, morphology, and particle sizes of nano powders were
      characterized by a thermal analysis (TG-DTA), X-ray diffraction (XRD), a field
      emission scanning electron microscopy (FE-SEM), and a particle size analyzer,
      respectively LaCrO3 powders were mainly orthorhombic in structure and the primary
      particle size was 30 nm according to the XRD results. All solid-state compact
      impedancemetric-type sensor devices composed of Li1.5Al0.5Ti1.5(PO4)3 (LATP) as a
      transducer and a perovskite-type LaCrO3 nano powder as a receptor, have been
      investigated for their ability to detect NOx (NO and NO2) in the range of 1-250
      ppm at 400 degrees C. The sensor device showed high gas sensitivities at NO gas,
      but relatively low gas sensitivities for NO2 gas.

PMID- 22629911
TI  - Parameter optimization for positive dielectrophoretic trapping force on ZnO
      nanoparticles through simulation.
AB  - A numerical model of an ethanol droplet system containing ZnO nanoparticles was
      developed using finite element analysis. The spatial, voltage, and frequency
      dependence of positive dielectrophoretic trapping mechanism was analyzed with all
      the AC electrokinetic forces incorporated into our calculation. The AC
      electrokinetic forces were analyzed individually, compared, and analyzed
      collectively. The characteristic behavior of each phenomenon was demonstrated,
      and dielectrophoresis was shown to be the dominant force near the edges of
      electrodes. Through time evolution study of the particle concentration in the
      collective analysis, we calculated optimal values of voltage and frequency at
      which the dielectrophoretic trapping mechanism is the most effective. This
      versatility of our numerical model promises its potential application in
      parameter optimization.

PMID- 22629910
TI  - Effect of NiZnFeO4 content on PZT-pZN + NiZnFeO4 magnetoelectric composite.
AB  - We fabricated and characterized the magnetoelectric (ME) properties of 3-0 ME
      composite materials comprised of the high piezoelectric voltage coefficient
      material, 0.9Pb(Zr0.52Ti0.48)O3-0.1 Pb(Zn1/3Nb2/3)O3 + 0.005Mn (PZT-PZN), and the
      magnetostrictive material, Ni0.8Zn0.2Fe2O4 (NZF). As the ME effect is generated
      by the product coupling between the piezoelectric properties and the
      magnetostrictive properties, the NZF content should be optimized for a higher ME
      coefficient. The dielectric constant and spontaneous polarization (P) were
      decreased with increasing NZF content before the percolation of the NZF
      particulates. However, as the NZF content exceeded the percolation content, the
      dielectric loss was dramatically increased due to the low resistivity of NZF.
      While the piezoelectric constant was decreased with increasing NZF content, the
      maximum magnetization was linearly increased. When we combined the piezoelectric
      and magnetostrictive effects, the ME composite sintered at 1200 degrees C with
      20% NZF showed a maximum dE/dH of 27 mV/cm x Oe at a magnetic bias of 1240 Oe.

PMID- 22629912
TI  - Mathematical analysis of thermoelastic characteristics in plasma-sprayed thermal
      barrier coatings.
AB  - The thermoelastic characteristics of plasma-sprayed thermal barrier coatings
      (TBCs) have been analyzed using mathematical modeling. Two types of TBC model,
      cylinder and circular disk which are commercial plasma-sprayed TBCs, subjecting
      to symmetric temperature distribution to the radial and longitudinal directions,
      respectively, were taken into consideration. Based on the thermoelastic theories,
      a second order ordinary differential equation was derived for the cylinder model
      and a pair of partial differential equations were set up for the circular disk
      model. The analytic solution was obtained from the ordinary differential
      equation, while a finite volume method was developed for numerical solutions to
      the pair of partial differential equations due to the complexity of governing
      equations. The thermoelastic characteristics of TBC models, such as temperature
      distributions, displacements, and stresses, were displayed according to the
      obtained solutions. The rate of heat conduction in the section of the top coat is
      relatively slow in comparison with the substrate, and no profound difference
      appears in the temperature distribution between two TBC models. The highest
      longitudinal tensile stress is expressed at the bond coat of both models, and the
      substrate is under the compressive stresses to the circumferential direction.
      While the cylinder expands to the positive longitudinal direction only, the
      expansion in the circular disk occurs to both the positive and negative
      longitudinal directions. Relatively large displacement and stresses exhibit in
      the cylinder as compared with the circular disk. In the circular disk, the
      stresses to the radial direction undulate at each section, and the displacement
      profile displays that the width of the circular disk is slightly narrowed. The
      results demonstrate that the mechanical and thermal properties of the top and
      bond coats are the crucial factors to be considered in controlling the
      thermoelastic characteristics of plasma-sprayed TBCs.

PMID- 22629913
TI  - Effect of solution-processed niO thin film as a hole transport layer in poly(3
      hexylthiophene): [6,6]-phenyl C61-butyric acid methyl ester bulk heterojunction
      solar cells.
AB  - In this study, solution-processed nickel oxide (NiO) thin film was investigated
      as a hole transport layer on anode to improve the performance of bulk
      heterojunction solar cell based on poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl
      C61-butyric acid methyl ester (PCBM). We fabricated NiO thin film without any
      vacuum-related process. Characterization of the NiO film under this study shows
      that it has maximum transmittance of 93.22% and bandgap of 3.84 eV which are
      proper for solar cell. Insertion of the NiO layer affords to realize enhanced
      power conversion efficiency of 1.97% and fill factor of 52.11% showing
      improvement over existing cells. In addition, NiO suggests one solution of
      minimizing conventional problems of poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) such as interfacial
      power losses, corrosion of indium tin oxide layer, and degradation of the
      devices. The value of such hole transporting and electron blocking properties is
      clearly demonstrated and could be applicable to other organic photovoltaics.

PMID- 22629914
TI  - Study on the micro-heater geometry in In,2O3 micro electro mechanical systems gas
      sensor platforms and effects on NO2 gas detecting performances.
AB  - Micro electro mechanical systems (MEMS) platforms for gas sensing devices with
      the co-planar type micro-heaters were designed, fabricated and its effects on the
      In2O3 gas sensors were investigated. Micro-heaters in MEMS gas sensor platforms
      were designed in the four-type heater patterns with different geometries. Electro
      thermal characterizations showed that the designed platforms had highly thermal
      efficiency because the micro hot-plate structures were formed in the diaphragm
      and the thermal efficiencies were analyzed for all of 16 models and compared with
      each other, respectively. The designed micro-platforms were fabricated by MEMS
      process, and Indium oxide (In2O3) nanoparticles were synthesized by sol-gel
      process and dropped on the MEMS platforms for detecting the noxious oxide gas
      (NO2) Fabricated micro-platforms had a very low power consumption in the
      fabricated 16-type models, especially, the minimum power consumption was 41 mW at
      the operating temperature of 250 degrees C. After experiments on gas sensing
      characteristics to NO2 gases, fabricated In2O3 gas sensors had almost the same
      gas sensitivity (Rs) at the operation temperature of 250 degrees C. It is
      concluded that the micro-heater geometries, pattern shapes and sizes, can be
      influential on the power consumption of the devices and its gas sensing
      characteristics.

PMID- 22629915
TI  - Fabrication of a pure TiO2 thin film using a self-polymeric titania nano-sol and
      its properties.
AB  - A pure TiO2 thin film without adding any organic binder was fabricated by using a
      self-polymeric titania nano-sol (14 mass%), which was prepared by the acid
      peptization method. The particle size distribution in the 14 mass% TiO2 sol, in
      which almost of particles had a size below 10.2 nm and the crystal phase
      confirmed by X-ray diffraction analysis was anatase. The diluted nano-sol had a
      capability to form a thin film at a low temperature (100-400 degrees C) on the
      slide glass by dipping method. The average thickness of a coating film was
      measured to be about 0.25-0.30 microm. A coated film had a high refractive index
      over 1.88 at least irrespective of the heat-treatment even at room temperature
      drying and showed a super-hydrophilicity (< 5 degrees) after 20 minutes under
      Ultra Violet light irradiation, and it sustained in the darkness during a long
      period over 7 days depending on the heat-treatment conditions. Atomic Force
      Microscopic observation shows that the morphology of a heat-treated film had a
      relationship with the long-term hydrophilicity in the darkness.

PMID- 22629916
TI  - Fabrication of transparent conductive electrode film using thermal roll-imprinted
      Ag metal grid and coated conductive polymer.
AB  - In this study, to fabricate a low-resistance and high optical transparent
      conductive electrode (TCE) film, the following steps were performed: the design
      and manufacture of an electroforming stamp mold, the fabrication of thermal-roll
      imprinted (TRI) poly-carbonate (PC) patterned films, the manufacture of high
      conductivity and low-resistance Ag paste which was filled into patterned PC film
      using a doctor blade process and then coated with a thin film layer of conductive
      polymer by a spin coating process. As a result of these imprinting processes the
      PC films obtained a line width of 10 +/- 0.5 Mm, a channel length of 500 +/- 2
      microm, and a pattern depth of 7.34 +/- 0.5 microm. After the Ag paste was used
      to fill part of the patterned film with conductive polymer coating, the following
      parameters were obtained: a sheet resistance of 9.65 Omega/sq, optical
      transparency values were 83.69% at a wavelength of 550 nm.

PMID- 22629917
TI  - Study on the resin layer formation according to the imprinting pressure rates.
AB  - The UV imprinting period and pressure magnitude are very important processing
      factors along with pattern shape and density of mold pattern. In the control
      process of the residual resin layer, the imprinting period and the magnitude and
      rate of the imprinting pressure should be properly assigned according to the
      density and shape of the mold pattern as well as resin viscosity etc. In this
      work, the imprinting time and pressure rate are studied for the formation and
      thickness variation of the residual resin layer. The thickness variation of the
      resin layer during imprinting process is computed according to the variation of
      the imprinting load rate, and some comparison results are successfully obtained
      with a 3-D shape of the mold patterns.

PMID- 22629918
TI  - Influence of interface layers on Ag thin film growth.
AB  - We prepared Ag thin films on SiO2/Si substrates, with and without a subnanometer
      thick organic interface layer of 3-mercaptopropyltrimethoxysilane (MPTMS). The
      surface morphology and electrical resistivity of these films were investigated
      and compared. Ag films grown with an MPTMS layer were relatively flat, resulting
      in a smaller critical thickness. This was probably because migration of Ag atoms
      on the substrate was suppressed by interactions between the Ag atoms and the
      thiol moiety. The deposition rate and terminating group of the organic interface
      layer also influenced the Ag film growth.

PMID- 22629919
TI  - Characteristics of nano-sized (Pb, La)TiO3 powder synthesized at room
      temperature.
AB  - We synthesized nano-sized (Pb, La)TiO3 powder using a high energy mechano
      chemical technique at room temperature. By the results, nano-sized (Pb, La)TiO3
      powder with perovskite structure was successfully synthesized from an oxide
      mixture using a high energy mechano-chemical technique without any post
      annealing. The mechanically-synthesized (Pb, La)TiO3 powder consisted of
      nanometer sized particles and had very high homogeneity. According to increase of
      milling time, source phases such as Pb oxides and TiO2 disappeared and the
      perovskite PLT phase was formed by chemical reaction and the release of OH group.

PMID- 22629920
TI  - Electrical and optical properties of NiO composite films by radio frequency
      magnetron sputtering.
AB  - The 100-nm NiO-Ag composite films with Ag content of 0 to 24.4 at.% are deposited
      on glass substrates. It is found that an ultra high electric resistivity (rho)
      value is obtained and cannot be detected by four point probe measurement when the
      Ag content is less than 3.4 at.%. The rho value is reduced significantly to 29.0
      Omega-cm as Ag content is increased to 4.2 at.%, and it decreases greatly to
      0.009 Omega-cm as the content of Ag is further increased to 24.4 at.%. The NiO-Ag
      composite film with Ag content of 4.2 at.% shows p-type conduction. However, it
      becomes n-type when the Ag content increases to 9.3 at.%, which results from the
      Ag atoms segregated at grain boundary of NiO when the excess Ag atoms are added
      into NiO films. On the other hand, the transmittance of the NiO-Ag films drops
      continuously from 96.3% to 31.6% as the Ag content increases from 0 to 24.4%.

PMID- 22629921
TI  - Electromagnetic response of superconductors with pinned vortices.
AB  - Some features of the vortex lattice in type-II superconductors and of its pinning
      and thermally activated depinning are given. Manipulation of a pinned single
      vortex by the tip of a Magnetic Force Microscope is mentioned. Statics and
      dynamics of pinned vortices in thick and thin strips and disks, and in
      rectangular plates, can be computed from continuum theory.

PMID- 22629922
TI  - Controlled thicknesses of vaporized self-assembled multilayers on copper
      nanopowders under ultra-high vacuum (UHV).
AB  - Copper nanoparticles were coated with 1-octanethiol self-assembled monolayers
      (SAMs) using the dry-coating method for oxidation prevention. In this study,
      thicknesses of 1-octanethiol SAMs were successfully controlled, and the stability
      of SAMs as a passivation layer on copper nanoparticles was examined. Thicknesses
      of 1-octanethiol SAMs varied with vacuum levels and coating cycles. Under low
      vacuum conditions, the thickness was 10 nm, regardless of the coating conditions.
      In contrast, various thicknesses resulted under ultra-high vacuum (UHV) and
      ranged from 4 nm to 10 nm. SAMs that were nearly a monolayer thick (4 nm)
      resulted from two coating cycles of 1.5 min, and the oxidation inhibition period
      was 15 days. Thus, the dry-coating method successfully controlled the thicknesses
      of SAMs with satisfactory oxidation inhibition properties under ultra-high
      vacuum.

PMID- 22629923
TI  - Fabrication of nano patterns on various substrates using nanosphere lithography
      technique.
AB  - This paper presents a procedure for fabricating large-area, size-tunable, metal
      arrays with a periodically different shape using Nanosphere Lithography (NSL).
      This technique has attracted considerable interest because of its important
      applications as diffraction devices, chemical and optical data recording. Their
      ordered arrays can be used for anti-reflection surfaces, bio-sensors and
      nanopatterning masks. Two different types of patterns, honeycomb and hexagonal
      patterns, could be fabricated on various substrates with different procedures.
      All steps for making different patterns employed a PS (polystyrene) monolayer by
      spin coating. Honeycomb patterns were fabricated by spin coating a PS monolayer
      on a glass substrate and depositing a metal followed by removal of the monolayer,
      whereas the hexagonal pattern was produced by the transfer of a gold deposited
      monolayer onto a GaN substrate using the same process. These processes allow
      simple and excellent control of the size and shape of the patterns. All
      experimental results on structure characterization and determination of the
      nanoparticle metrics were accomplished by atomic force microscopy and field
      emission-scanning electronic microscopy.

PMID- 22629924
TI  - High efficiency simple white phosphorescent organic light-emitting diodes using a
      phosphine oxide host.
AB  - Highly efficient simple white organic light-emitting diodes (WOLEDs) were
      fabricated using a mixed host of 1,1-bis[(di-4-tolylamino)phenyl]cyclohexane
      (TAPC) and 2,7-bis(diphenylphosphoryl)-9,9'-spirobi[fluorene] (SPPO13) in the
      light-emitting layer. A two layer WOLED structure of TAPC hole transport layer
      and TAPC:SPPO13 emitting layer was developed. Red and blue phosphorescent
      emitters were doped in the TAPC:SPPO13 mixed host emitting layer and a high
      quantum efficiency of 16.0% was obtained. In addition, the maximum power
      efficiency of the WOLEDs was 37.5 Im/W and color coordinate was (0.43, 0.41). The
      color coordinate could be kept stable irrespective of the luminance of the
      device.

PMID- 22629925
TI  - Structural control over self-assembled crystals of pi--conjugated poly(3,3'''
      didodecyl-quaterthiophene) for organic field-effect transistor applications.
AB  - Liquid-crystalline (LC) poly(3,3'''-didodecyl-quaterthiophene) (PQT-12) was
      investigated to optimize its side alkyl ordering and pi-conjugated structure for
      high performance organic field-effect transistor (OFET) applications. Initially,
      low-crystal films spun-cast on OTS-treated SiO2 substrates were further
      crystallized via either thermal or solvent treatments. At temperatures (125-138
      degrees C) driving a LC state of PQT-12, mobile chains were better migrated into
      preformed crystals. The resulting films showed highly crystal nanofibrils, in
      which pi-conjugated polymer backbones (with an conjugated backbone spacing,
      d(010) of 3.80 A) and the orientation of self-assembled side-chains were tilted
      with respect to the film surface, respectively. However, via melting or solvent
      exposure providing isotropic states, film crystallization generated less ordered
      crystals with randomly oriented side-chains, increasing d(010) up to 4.16 A. As a
      result, the usage of LC characteristic allowed us to consistently achieve the
      desirable crystal structure of PQT-12 and to robustly obtain high field-effect
      mobility for FET applications.

PMID- 22629926
TI  - Characteristics of protein-polymer nanobiocomposite films for protein devices.
AB  - Here we report the characteristics of protein-polymer nanobiocomposite films and
      their solid state devices. The protein-polymer nanobiocomposite films (thickness
      = approximately 125 nm) were prepared by spin-coating the solution of cytochrome
      c (cyt c) and poly(vinyl alcohol) (PVA) (cyt c:PVA = 3:1 by weight). To
      understand the characteristics of the cyt c-PVA films (nanolayers), we employed
      the optical absorption and surface morphology measurement and then fabricated
      planar diode-type solid state devices. The optical absorption measurement showed
      that the heme part of cyt c in the cyt c-PVA nanolayer was well kept after the
      coating process, while the crack-like surface was found from the atomic force
      microscopy measurement. The planar device showed an ohmic type dark current, but
      the current gradually increased as the incident light intensity increased. In
      particular, the (photo) current was strongly dependent upon the voltage, which
      was assigned to the insulating role of cyt c surrounding groups and PVA. This
      trend was supported by the slow rise and decay time via photo-switching
      experiment.

PMID- 22629927
TI  - Effect of bath type on the formation of TiO2 nanotubes in fluoride containing
      aqueous solution.
AB  - TiO2 nanotubes were formed on Ti electrochemically by the application of anodic
      current in 1 M H3PO4 + 0.3 M HF solution in a glass and Teflon bath. The TiO2
      nanotubes could be partly grown in the glass bath while a uniform growth of TiO2
      nanotubes was observed over the whole surface in the Teflon bath. The TiO2
      nanotubes fabricated in the glass bath broke off readily during ultrasonic
      cleaning in distilled water while the TiO2 nanotubes formed in the Teflon bath
      was not damaged by the ultrasonic cleaning up to 5 minutes. The ultrasonic
      cleaning could remove the surface residuals which are obtained inevitably if TiO2
      nanotubes are fabricated in aqueous solutions.

PMID- 22629928
TI  - Inverted organic solar cells with ZnO nanowalls prepared using wet chemical
      etching in a KOH solution.
AB  - We report on the photovoltaic (PV) performances of inverted organic solar cells
      (IOSCs) that were fabricated from PCBM:P3HT polymer with a ZnO thin film and ZnO
      nanowalls as electron transport and hole block layers. ZnO thin film on ITO/glass
      substrate was deposited using a simply aqueous solution route. ZnO nanowall
      structures were obtained via wet chemical etching of ZnO thin films in a KOH
      solution. The power conversion efficiency (PCE) of the IOSC with ZnO nanowalls
      was significantly improved by 44% from 1.254% to 1.811% compared to that of the
      IOSC with ZnO thin film. The short circuit current in IOSCs fabricated with the
      ZnO nanowalls was increased mainly due to the increase in the charge transport
      interface area, as a result of enhancement in the PCE. This work suggests a
      method for fabricating efficient PV devices with a larger charge transport area
      for future prospects.

PMID- 22629929
TI  - Iron doped hexagonal ErMnO3: structural, magnetic, and dielectric properties.
AB  - The single phase ErFe(x)Mn1-xO3 (0 < or = x < or = 0.15) compounds were
      synthesized by the solid-state reaction method. The doping effects on the crystal
      structural, magnetic, thermal, and dielectric properties were systematically
      investigated. The XRD patterns show all samples crystallize in the hexagonal
      structure with P6(3)cm space group. The lattice parameters a and c first decrease
      with doping, which is followed by a subsequent increase at higher doping levels.
      Although both the Fe3+ and Mn3+ ions remain stable in high spin trivalent states
      in all samples, the magnetization is weakened with increasing Fe contents. The
      heat capacity data shows the antiferromagnetic transition slightly shifts from 77
      K for ErMnO3 to 80 K for ErFe015Mn0.85O3, which can not be observed in the
      magnetic susceptibility data. The real part of complex impedance of these samples
      rises as the doping level increases, indicating the enhancement of insulativity
      of doped samples.

PMID- 22629930
TI  - Fabrication of triple-layered magnetite-hydrogel-gold nanocomposites for
      biomedical applications.
AB  - Magnetite-hydrogel-gold nanocomposites with optical-active, thermo-responsive,
      and magnetism have been prepared by the following consecutive steps. Hydrogel
      encapsulated magnetites were first synthesized by the combination of sol-gel
      reaction and radical polymerization process, and the resulting magnetic hydrogels
      were subsequently bound with nano-sized Au (1-3 nm) via a molecular linkage of
      diamine ligand which was covalently bonded to the carboxylic groups on the
      hydrogel surface. Au seeds anchored on the magnetic hydrogels were further
      reduced into nano-scale Au layer which induced the distinct red-shift of
      absorption band into NIR region. The optical properties and surface morphology of
      the nanocomposites were characterized by UV-vis spectroscopy, scanning electron
      microscopy (SEM), and transmission electron microscopy (TEM).

PMID- 22629931
TI  - Enhanced cycling performance of nanocrystalline Fe3O4/C as anode material for
      lithium-ion batteries.
AB  - Fe3O4-carbon composite was prepared by the sol-gel method. The crystal structure,
      morphology, and phases present in the product were investigated by X-ray
      diffraction and by scanning electron microscopy (SEM) combined with energy
      dispersive X-ray spectroscopy and field-emission SEM. Electrochemical
      characterization was performed using constant current charge-discharge testing
      and electrochemical impedance spectroscopy. The Fe3O4/C electrode has high
      initial columbic efficiency (87%) and outstanding cycling performance (775.3 mAh
      g(-1) after 90 cycles at a current density of 100 mA g(-1)).

PMID- 22629932
TI  - Processing technique for single-walled carbon nanotube-based sensor arrays.
AB  - We investigated a selective assembly method of fabricating single-walled carbon
      nanotubes (SWCNTs) on a silicon-dioxide (SiO2) surface by using only a
      photolithographic process; then, we fabricated 8 x 8 field-emission transistor
      (FET) arrays for sensor applications. Photoresist (PR) patterns were made on a
      SiO2-grown Si substrate by using the photolithographic process. This PR-patterned
      substrate was dipped into a SWCNT solution dispersed in dichlorobenzene (DCB).
      The PR patterns were removed by using acetone. As a result, selectively-assembled
      SWCNT channels in 8 x 8 FET arrays could be fabricated between source and drain
      electrodes without complicated chemical steps using octadecyltrichlorosilane
      (OTS). Finally, we successfully fabricated 8 x 8 SWCNT-based multi-channel FET
      arrays by using our novel self-assembly method.

PMID- 22629933
TI  - Macroscopic and microscopic investigation on chemical mechanical polishing of
      sapphire wafer.
AB  - Sapphire (alpha-Al2O3) is an important ceramic material that is widely used in
      substrate material for electronics. We investigate the chemical reaction layer on
      a sapphire wafer using X-ray photoelectron microscopy (XPS) and atomic force
      microscopy (AFM). The frictional characteristics of sapphire chemical mechanical
      polishing (CMP) was studied using in-situ friction force monitoring system. From
      XPS analysis and AFM experiment, a chemically-reacted layer was verified on the
      sapphire surface through a chemical reaction between the sapphire and chemicals
      in a slurry. During sapphire CMP, the friction force mainly depended on the
      applied pressure. The material removal efficiency per unit friction energy in
      sapphire CMP was 6.18 nm/kJ.

PMID- 22629934
TI  - Mass production of polyfluorene nanowires using a melt-assisted wetting method.
AB  - Herein is a description of the mass production of poly(9, 9-dioctylfluorene-co
      benthiadiazole) (F8BT) and poly(9, 9-dioctylfluorene) (PFO) nanowires (NWs) using
      a melt-assisted wetting method with an anodic alumina membrane. The conjugated
      polymer NWs had a uniform shape (D = 250-300 nm/L = 10-30 microm) and a defect
      free smooth surface. Optical properties were investigated by UV-vis,
      photoluminescent spectroscope, and fluorescent optical microscope. Individual
      F8BT and PFO NWs had a bright yellow (lambda = 541 nm) andblue (lambda = 442 nm)
      luminescence, respectively, under UV light irradiation.

PMID- 22629935
TI  - Synthesis and photophysical studies of blue phosphorescent Ir(III) complexes with
      dimethylphenylphospine.
AB  - New blue emitting mixed ligand iridium(III) complexes comprising one
      cyclometalating, two phosphines trans to each other such as
      Ir{(CF3)2Meppy}(PPhMe3)2(H)(L) [L = CI, NCMe, CN] [(CF3)2Meppy = 2-(3', 5'-bis
      trifluoromethylphenyl)-4-methylpyridine] were synthesized and studied to tune the
      phosphorescence wavelength to the deep blue region and to enhance the
      luminescence efficiencies. To achieve deep blue emission, the trifluoromethyl
      group substituted on the phenyl ring and the methyl group substituted on the
      pyridyl ring increased HOMO-LUMO gap and achieved the hypsochromic shift. To gain
      insight into the factors responsible for the emission color change and the
      different luminescence efficiency, we investigate the electron-withdrawing
      capabilities of ancillary ligands using the DFT and TD-DFT calculations on the
      ground and excited states of the complexes. From these results, we discuss how
      the ancillary ligand influences the emission peak as well as the metal to ligand
      charge transfer (MLCT) transition efficiency. The maximum emission spectra of
      Ir{(CF3)2Meppy}(PPhMe3)2(H)(Cl), [Ir{(CF3),Meppy)(PPhMe3),(H)(NCMe)]+ and
      Ir{(CF3)2Meppy}(PPhMe3)2(H)(CN) were in the ranges of 441, 435, 434 nm,
      respectively.

PMID- 22629936
TI  - New polymeric buffer materials with low driving voltage.
AB  - We present excellent polymeric buffer materials based on the poly(9,9
      dioctylfluorene-co-N, N-di(phenyl)-N,N-di(3-carboethoxyphenyl)benzidine) (BFE)
      for highly efficient solution processed organic light emitting diodes (OLEDs).
      Doped BFE with 3,5-dinitrobenzonitrile (35DNBN), a strong electron acceptor
      results in significant improvement of current flow and driving voltage. Maximum
      current- and power-efficiency value of 7.2 cd/A and 5.5 lm/W are demonstrated
      from blue OLEDs with these doped polymeric anode buffer system. The 40 nm thick
      anode buffer material showed a similar current density-voltage (J-V) behavior to
      that of PEDOT:PSS based device. Results reveal a practical way to fabricate the
      highly efficient solution processed devices for low cost production of printing
      devices for the future.

PMID- 22629937
TI  - Electrochemiluminescence cell fabrication using TiO2 nanotube produced by anodic
      oxidation.
AB  - Electrochemiluminescence (ECL) cell using the electrode of TiO2 nanotube (NT) and
      Ru(ll) complex Ru(bpy)3(PF6)2 as a luminacence substance was fabricated. TiO2 NT
      were produced from the membrane of TiO2 NT arrays fabricated by anodic oxidation
      of approximately 100 microm thick Ti-plate. TiO2 NT arrays inject increasing
      number of electrons to the Ru(II) complex at the interface of TiO2 NTs. It allows
      the increasing exergonic oxidation/reduction reaction of Ru(II) complex. The ECL
      cell emits approximately 600 nm light in orange color. The cell structure is
      composed of a glass/F-doped SnO2(FTO)/TiO2 NT/Ru(II) complex in propylene
      carbonate/FTO/glass. The ECL efficiency of the cell consisting of the layer of
      TiO2 NT was approximately 255 cd/m2 at a bias of 4 V. The use of TiO2 NT
      increases ECL intensities by 5 times compared to the typical ECL cell without the
      use of TiO2 NT.

PMID- 22629938
TI  - Post treatment of plasma-polymerized SnOx organic-like films with poly ethylene
      glycol for improving CO gas sensitivity.
AB  - In this study, a new room temperature type gas sensor device based on plasma
      deposition of tetramethyltin (TMT) and O2 organically hybridized film followed by
      post treatment on the deposited film was developed for improving CO gas
      sensitivity and distinguishing from methane, butane, and carbon monoxide gases in
      the test environment. Plasma deposited SnOx thin film was first produced from TMT
      and O2 gas mixtures at room temperature, and then post treatments on the SnOx
      thin films were carried out by either spin coating with poly ethylene glycol
      (PEG) or surface grafting with p-styrenesulfonic acid sodium salt (Nass). It was
      found that the gas sensor spin coating post treated with PEG exhibits linear
      response to CO gas with the sensitivity not affected by methane and butane gases.
      For CO concentrations ranging from 30 to 650 ppm, steep change in the sensor
      resistance can be detected without warming up the sensor.

PMID- 22629939
TI  - Microstructure and electrical property of TiNx films deposited by DC reactive
      magnetron sputtering superimposed electromagnetic field system.
AB  - TiNx films were successfully deposited by DC reactive magnetron sputtering
      superimposed EMF system without substrate heating. In case of DCMS 400 W+ EMF 25
      W, electrical property, reflectance and crystallinity of the TiN films were
      clearly improved by the enhancement of nitrification. The lowest sheet resistance
      of 2.9 Omega/? (resistivity 5.8 x 10(-5) Omegacm) was observed for the film
      deposited at F(N)2: 16%. Mixture phases of the (111) plane and (200) plane showed
      lower resistivity than only (200) single phase. Therefore it is confirmed that
      introduction of EMF system is promising technology to deposit TiN film.

PMID- 22629940
TI  - Synthesis of NiO nanofibers and their gas sensing properties.
AB  - NiO nanofibers were synthesized by an electrospinning method with polyvinyl
      alcohol and nickel acetate tetrahydrate as precursor materials. Individual
      nanofibers consisted of nanograins. A gas sensor has been fabricated using these
      nanofibers. Its sensing properties to NO2 and benzene were investigated. The
      sensor exhibited good sensitivity and dynamic properties for the tested gases.
      All these results suggest that the electrospinning-synthesized NiO nanofibers
      hold promise for realizing sensitive and reliable gas sensors.

PMID- 22629941
TI  - Nanostructured TiO2-coated activated carbon composite as an electrode material
      for asymmetric hybrid capacitors.
AB  - A nanostructured TiO2-coated activated carbon (TAC) composite was synthesized by
      a modified sol-gel reaction and employed it as a negative electrode active
      material for an asymmetric hybrid capacitor. The structural characterization
      showed that the TiO2 nano-layer was deposited on the surface of the activated
      carbon and the TAC composite has a highly mesoporous structure. The evaluation of
      electrochemical characteristics of the TAC electrode was carried out by
      galvanostatic charge/discharge cycling tests and electrochemical impedance
      spectroscopy. The obtained specific capacitance of the TAC composite was 42.87
      F/g, which showed by 27.1% higher than that of the activated carbon (AC). The TAC
      composite also exhibited an excellent cycle performance and kept 95% of initial
      capacitance over 500 cycles.

PMID- 22629942
TI  - Electrochromic properties of tungsten-titanium oxide films.
AB  - The last decade has seen great in electrochromic (EC) technology for smart
      windows and displays. In this study, WTiOx films formed from TiO2 and WO3 were
      deposited onto ITO glass with a sheet resistance of 10 Omega cm and on silicon
      substrates, by pulsed magnetron sputtering using a W and Ti alloy target. The
      films were deposited at plasma powers 100, 200, 300, 400 and 500 W using a
      gaseous Ar (150 sccm)/O2 (50 sccm) mixture; the working pressure was fixed at 5E
      2 torr. The film thickness increased with the plasma power. However, increasing
      the plasma power yielded a more crystalline structure with poorer electrochromic
      properties. The influence of Ti doping and plasma power on the structural,
      optical and electrochromic properties of the WTiOx thin films was studied. WTiOx
      films grown at various plasma powers of under 400 W were amorphous. Deposition of
      films at 400 W yielded the optimal electrochromic properties, with high optical
      modulation, high coloration efficiency and the lowest color memory effect at
      wavelengths 400, 550 and 800 nm. An XPS study indicated that Ti can stabilize the
      valence state of W6+. The improvements caused by the doping with Ti were tested:
      an optical density (OD) of close to 0.85 and a maximum delta T (%) at 400 nm of
      25.8%, at 550 nm of 52.5% and at 800 nm (in the near-IR region) of 62.4%.

PMID- 22629943
TI  - Microstructure and magnetic properties of nano-sized Ba-Al ferrite particles by
      high energy ball milling.
AB  - The magnetic nano-structured Ba-Al ferrite powders were prepared by high energy
      ball milling under the conditions of various rotation rates and milling times.
      The micro structure was characterized by SEM, XRD and TEM, and the magnetic
      properties were obtained by VSM. As the rotation rate and milling time increased,
      the size of nano-sized particles gradually decreased. The high energy ball
      milling for 5 h without relation to the rotation rate drastically reduced the
      coercivity as a consequence of the formation of nano-sized particle with the
      amorphous structure. However, the coercivity gradually decreased with increasing
      the milling time, resulting from the decrease of particle size with maintaining
      the crystal structure.

PMID- 22629944
TI  - Surface modified TiO2 nanostructure with 3D urchin-like morphology for dye
      sensitized solar cell application.
AB  - Three-dimensional (3D) urchin-like rutile TiO2 powders were synthesized by a mild
      hydrothermal method without any templates. An individual urchin-like TiO2 powder
      consists of self-assembled nanorods with a length of about 150 nm and width of
      about 10 nm. Additionally, the urchin-like TiO2 nanopowders were coated with an
      ultra-thin ZnO layer in order to modify the surface properties of the
      nanopowders, and the ZnO layer was confirmed by high-resolution transmission
      electron microscopy (HRTEM) and X-ray photoelectron spectroscopy (XPS) analysis.
      The ZnO-modified TiO2 was used as a photoelectrode of a dye-sensitized solar cell
      (DSSC) and the solar cell performances were investigated. In comparison with bare
      TiO2, ZnO-modified TiO2 improved the photovoltaic performances, i.e., energy
      conversion efficiency, open circuit voltage, and short circuit current were
      increased. The higher DSSC performance of ZnO-modified TiO2 was attributed to its
      higher dye loading and lower charge recombination rate.

PMID- 22629945
TI  - Properties of high-energy ball-milled Fe-Se based superconductors.
AB  - We have synthesized FeSe0.5Te0.5 superconductors by high-energy ball-milling and
      subsequent annealing. High-energy ball-milling of elemental powder mixtures
      resulted in the formation of metastable and/or nanocrystalline phases. Both XRD
      and DSC results show that the ball-milled powers were completely transformed to
      FeSe0.5Te0.5 with the grain size of a few nanometers during sintering at low
      temperatures. The resulting materials exhibited superconducting transition at 14
      K. The enhancement of critical current density was observed for the high-energy
      ball-milled powder, compared with the un-milled powders.

PMID- 22629946
TI  - One-step spray pyrolysis synthesized CuO-carbon composite combined with
      carboxymethyl cellulose binder as anode for lithium-ion batteries.
AB  - Copper oxide-carbon composite with hollow sphere structure has been synthesized
      by a one-step spray pyrolysis method and tested as anode material for lithium-ion
      batteries. Different analytical methods, including X-ray powder diffraction,
      scanning electron microscopy, energy-dispersive X-ray spectrometry,
      thermogravimetric analysis, and systematic electrochemical tests were performed.
      The results demonstrate that the CuO-carbon composite in conjunction with
      carboxymethyl cellulose (CMC) binder has an excellent electrochemical
      performance, with a capacity of 577 mAh g(-1) up to 100 cycles. The usage of the
      water soluble binder, CMC, not only obviously improves the electrochemical
      performance, but also makes the electrode fabrication process much easier and
      more environmentally friendly.

PMID- 22629947
TI  - Fabrication and optical emission of TiO2-sheathed ZnO nanowires.
AB  - The ZnO nanowires were synthesized by using vapor-liquid-solid mechanism and then
      the ZnO nanowires were sheathed with TiO2 by metal organic chemical vapor
      deposition. The coaxial nanowires were 30-200 nm in diameter and up to 0.2 microm
      in length. Transmission electron microscopy and X-ray diffraction analysis
      results showed that the ZnO cores and TiO2 shells of the core-shell nanowires had
      wurtzite and amorphous structures, respectively. Photoluminescence measurement
      showed that TiO2 coating increased and decreased the near-band edge (NBE) and
      deep-level emissions of the ZnO nanowires in intensity, respectively. However, it
      appeared that subsequent annealing was undesirable since it decreased the NBE
      emission in intensity.

PMID- 22629948
TI  - Photoluminescence enhancement of synthesized ZnS-based-nanocrystals and aging
      effect on its emitting color.
AB  - Various colors-emitting ZnS:Cu,Cl, ZnS:Cu,Cl,Mn and ZnS:Mn nanocrystals (NCs)
      which were shown to be about 3 nm sized-particle were synthesized by using a
      solution chemistry. And the luminescences of the synthesized ZnS-based NCs were
      investigated through photoluminescence excitation (PLE) and photoluminescence
      (PL) spectroscopy. The PLE and PL intensities of the ZnS-based NCs depends on
      their reflux time, and red shifted maximum PLE wavelengths of the synthesized NCs
      showed with increasing reflux time. The increased maximum PL intensity of NCs
      with increasing reflux time is due to the enhanced crystallinity of the NCs. And
      the shifted emitting colors of the NCs showed after aging treatment compared to
      those of refluxed NCs. The amount of shifted wavelength of Cu,CI doped ZnS, Cu,CI
      and Mn co-doped ZnS, only Mn doped ZnS NCs were -22 nm, +18 nm, and +14 nm,
      respectively.

PMID- 22629949
TI  - Hydrothermal synthesis of ZnO nanorods in the presence of a surfactant.
AB  - Controlling the dimensions, positioning, and shapes of semiconductor nanowires,
      nanorods, and nanobelts lies in the synthesis and understanding of their growth
      mechanism. Controlled growth and synthesis is required in the fabrication of
      nanodevices and nanosensors. Among methods utilized for one-dimensional
      nanostructure synthesis, the hydrothermal process--a simple and cost-effective
      technique involving a low process temperature--has emerged as a powerful tool for
      the fabrication of anisotropic nanomaterials. Under hydrothermal conditions, many
      starting materials can undergo quite unexpected reactions, which are often
      accompanied by the formation of nanoscopic morphologies that are not accessible
      by classical routes. Synthesized ZnO nanostructures from aqueous solutions are
      usually poor in terms of morphology and size control. To improve the growth
      conditions and the controllability of the process, the use of surfactants or
      organic solvents has been attempted. In the present work, ZnO nanorods were grown
      on templates with a pre-sputtered ZnO seed layer over oxidized Si (100)
      substrates, and polyvinyl pyrrolidone (PVP) was used as a surfactant. By varying
      the PVP concentration in the growth solution, we can control the diameter and
      density of ZnO nanorods. The optical property of ZnO nanorods is highly improved
      by PVP addition.

PMID- 22629950
TI  - Microstructure and mechanical properties of Al2O3 composites with surface-treated
      carbon nanotubes (CNTs): dispersibility of modified carbon nanotubes (CNTs) on
      Al2O3 matrix.
AB  - Aluminum oxide (Al2O3) matrix have been reinforced by the multi-walled carbon
      nanotubes (MWCNTs) to overcome the inherent brittleness of Al2O3 matrix. In order
      to increase mechanical properties of MWCNTs-Al2O3 composites, MWCNTs need to be
      well dispersed and individually incorporated in Al2O3 matrix. In this work,
      aluminum hydroxide (Al(OH)3) used as a Al2O3 precursor and MWCNTs were mixed in
      an aqueous solution for the homogeneous mixing of hetero-particles, as functions
      of the content of MWCNTs and the potential hydrogen (pH) of Al(OH)3 suspension.
      Firstly, MWCNTs were purified and modified by an acid reagent, inducing that the
      dispersibility of MWCNTs is increased in an aqueous solution by carboxylic group
      given on the surface of MWCNTs. The modified MWCNTs were added in the Al(OH)3
      suspension, and then the mixture was filtered at room temperature. The filtered
      powders were formed using an uniaxial pressing and then densified by a
      pressureless heat treatment. As the pH is decreased the Al(OH)3 particles are
      well dispersed in an aqueous solution, due to the increment of repulsive force
      between particles with a same surface charge. MWCNTs are individually
      incorporated into Al2O3 matrix up to 1 vol.% MWCNTs, whereas MWCNTs are
      aggregated at the composite with 3 vol.% MWCNTs. Therefore, control of the pH and
      the MWCNTs content are key factors to be considered for the fabrication of MWCNTs
      Al2O3 composites with high functional properties.

PMID- 22629951
TI  - Study on the microstructures and the magnetic properties of precipitates in a
      Cu75-Fe5-Ni20 alloy.
AB  - The microstructural evolutions of precipitates formed in a Cu75-Fe5-Ni20 alloy on
      isothermal annealing at 873 K and 1073 K have been investigated by means of
      transmission electron microscopy (TEM). Nano-scale magnetic particles were formed
      randomly in the Cu-rich matrix after receiving a short annealing due to phase
      decomposition in the alloy. With increasing the isothermal annealing time,
      however, the striking features that two or more nano-scale particles with a cubic
      shape and a rod shape were aligned linearly along (100) directions were observed
      on isothermal annealing at 873 K and 1073 K, respectively. To investigate electro
      magnetic properties of precipitates in a Cu-Fe-Ni alloy, the superconducting
      quantum interference device (SQUID) magnetometer and physical property
      measurement system (PPMS) were also complemented. The present study revealed
      significant influences that the magnetic properties of the specimens were closely
      related to the microstructures in the Cu-Fe-Ni alloy, which microstructures
      significantly depend on the isothermal annealing temperature.

PMID- 22629952
TI  - Light guide of Au nanostructures for color-filterness optoelectronic display
      devices.
AB  - Au line nanostructures with different pitch distances from 500 nm to 950 nm on
      ITO coated glass substrates have been fabricated at room temperature for
      exploring the color light guide in all kinds of display system. The patterned Au
      line array is used as a light outcoupling and color-selection component due to
      the emission wavelength changed by the Au line arrays with different pitch
      distances that could achieve multi-color selections. The ITO coated glass
      substrates patterned with periodic Au line arrays with controlled line pitches
      has been demonstrated and used as a color filter in all display devices. Using a
      proper pitch distance of Au line nanostructures, the basic third colors of red,
      green, and blue (RGB) can be simply gained and controlled without a traditional
      color filter for future optoelectronic display devices.

PMID- 22629953
TI  - Memory effect of low-temperature processed ZnO thin-film transistors having
      metallic nanoparticles as charge trapping elements.
AB  - In this study, non-volatile memory effect was characterized using the single
      transistor-based memory devices based on self-assembled gold nanoparticles (AuNP)
      as the charge trapping elements and atomic-layer deposited ZnO as the channel
      layer. The fabricated memory devices showed controllable and reliable threshold
      voltage shifts according to the program/erase operations that resulted from the
      charging/discharging of charge carriers in the charge trapping elements. Reliable
      non-volatile memory properties were also confirmed by the endurance and data
      retention measurements. The low temperature processes of the key device elements,
      i.e., AuNP charge trapping layer and ZnO channel layer, enable the use of this
      device structure to the transparent/flexible non-volatile memory applications in
      the near future.

PMID- 22629954
TI  - High performance flexible organic thin film transistors (OTFTs) with
      octadecyltrichlorsilane/ Al2O3/poly(4-vinylphenol) multilayer insulators.
AB  - The incorporation of a thin, atomic layer deposited Al2O3 layer in between a spin
      coated poly-4-vinyl phenol (PVP) organic layer and octadecyltrichlorsilane (OTS)
      in the multilayer gate dielectric for pentacene organic thin film transistors on
      a n(+)-Si substrate reduced the gate leakage current and thereby significantly
      enhanced the current on/off ratio up to 2.8 x 10(6). Addition of the OTS
      monolayer on the UV-treated Al2O3 improved the crystallinity of the pentacene
      layer, where the OTS/UV-treated Al2O3 surfaces increased their contact angles to
      100 degrees. X-ray diffraction (XRD) analysis revealed a more intense (001)
      crystal reflectance of pentacene deposited on OTS/UV-treated Al2O3 surface than
      that on OTS/Al2O3 surface. Moreover, the improved pentacene layer contributed to
      the field effect mobility (0.4 cm2/Vs) and subsequently improved the electrical
      performances of organic thin film transistor (OTFT) devices. This PVP/UV treated
      Al2O3/OTS multilayer gate dielectric stack was superior to those of the device
      with the single PVP gate dielectrics due to the improved crystallinity of
      pentacene.

PMID- 22629955
TI  - Microstructure and hardness of nano-sized Fe-based self-fluxing alloy powder with
      SiC particles.
AB  - The Fe-based self-fluxing alloy powders and SiC particles were mixed and milled
      by high energy ball-milling, and their microstructure and micro-hardness were
      investigated after subsequent compaction and sintering. The initial alloy powders
      with a mean size of approximately 80 microm were fined to 2.1 microm after
      milling at 800 rpm for 5 h. However, the powder mixture of alloy powder and SiC
      particle showed much larger powder size compared to the initial alloy powders.
      The bulk composites were obtained from the powder mixture by compaction under a
      pressure of 800 MPa for 10 min and sintering at 1073 K for 3 h. The composites
      had much higher micro-hardness of more than 700 Hv compared to alloy powder. The
      micro-hardness of composites slightly increased with the content of SiC
      particles.

PMID- 22629956
TI  - Synthesis of green emitting and transparent zn2siO4:mn2+ thin film phosphors on
      2D photonic crystal patterned quartz substrates.
AB  - Zn2SiO4:Mn2+ thin film phosphors (TFPs) have been synthesized by RF magnetron
      sputtering, using a single multicomponent stoichiometric target. And 2D photonic
      crystal patterns were introduced on a quartz substrate to enhance the light
      extraction efficiency. In order to introduce 2D photonic crystal patterns on a
      quartz substrate, nanosphere lithography was used. Polystyrene spheres, with
      diameter of 330 nm, were transferred on the quartz substrate and subsequently
      were served as an etch mask. Quartz substrates were patterned by CF4 gas-based
      reactive ion etching. Zn2SiO4:Mn2+ were deposited on that 2D photonic crystal
      patterned quartz substrate and the effect of height of photonic crystal layers
      were investigated. The light extraction efficiency of Zn2SiO4:Mn2+ thin film
      phosphors deposited on the photonic crystal patterned quartz substrate was
      enhanced three times to compared with that of flat Zn2SiO4:Mn2+ thin film
      phosphors due to the Bragg diffraction and leaky mode caused by PCLs.
      Transmittance of Zn2SiO4:Mn2+ TFPs deposited on the photonic crystal patterned
      substrate was high enough, above 70% in the visible light region with respect to
      that of quartz substrate.

PMID- 22629957
TI  - Phosphorescent blue organic light-emitting diodes with new bipolar host
      materials.
AB  - We report narrow band gap bipolar host materials, CbPr-3 (9,9'-[(3,3'-Biphenyl
      3.3'-yl-bipyridine)-1,3-biphenyl]bis-9H-carbazole) and Bim-4 (9,9'-[5-(1-phenyl
      1H-benzimadazol-2yl)-1,3-phenylene] bis-9H-carbazole), for blue phosphorescent
      OLEDs application. These two bipolar hosts have high triplet energy of > 2.9 eV,
      capable of reducing the driving voltages and improving efficiencies. Significant
      low driving voltages of 7.4 and 6.6 V were obtained for CbPr-3 and Bim-4 hosts,
      compared with 9.0 V of the commonly used host, mCP (1,3-bis(9
      carbazolyl)benzene). At a given constant luminance of 1000 cd/m2, the power
      efficiency of both the bipolar host devices was enhanced by 2.5 times.

PMID- 22629958
TI  - Introduction of the benzoquinoline ancillary ligand to the iridium complexes for
      organic light-emitting diodes.
AB  - The new iridium complexes, Ir(C^N)2(bq), (C^N = ppy, F2-ppy, 2,3-dpqx-F2 or 4-Me
      2,3-dpq) were prepared and their luminescence properties were investigated, where
      ppy, F2-ppy, 2,3-dpqx-F2, 4-Me-2,3-dpq and bq represent 2-phenylpyridine, 2
      (4',6'-difluorophenyl)-pyridine, 2,3-bis (4'-fluorophenyl)quinoxaline, 4-methyl
      2,3-diphenylquinoline and 10-hydroxybenzoquinoline ligands, respectively. We
      expected that the relative energy levels of the main ligands (C^N) and ancillary
      ligand, bq, in the complexes could determine the possibility of interligand
      energy transfer (ILET) in the complexes and thereby luminescence properties. The
      main ligands, F2-ppy and 2,3-dpqx-F2, which have drastically different energy
      gaps between the HOMO and LUMO energy levels were chosen and their complexes were
      synthesized. The photoabsorption, photoluminescence and electroluminescence of
      the complexes were studied. Ir(ppy)2(bq), Ir(F2-ppy)2(bq) Ir(2,3-dpqx-F2)2(bq)
      and Ir(4-Me-2,3-dpq)2(bq) exhibited the luminescence maxima between 600-694 nm
      and their efficiencies were affected by the main ligands. While Ir(ppy)2(bq) and
      Ir(F2-ppy)2(bq) showed relatively high luminous efficiencies (> 10 cd/A), Ir(2,3
      dpqx-F2)(bq) had poor luminous efficiency (0.30 cd/A). The electrochemical
      properties were studied to support ILET in the ppy-based iridium complexes. Their
      luminescence performances were compared with those of the complexes containing
      acetylacetonate (acac) ancillary ligand which are not allowed to have ILET.

PMID- 22629959
TI  - Doping-free fabrication of silicon thin films for schottky solar cell.
AB  - Thin film Schottky solar cells were fabricated without doping processes, which
      may provide an alternative approach to the conventional thin film solar cells in
      the n-i-p configuration. A thin Co layer was coated on a substrate, which worked
      as a back contact metal and then Si film was grown above it. Deposition condition
      may modulate the Si film structure to be a fully amorphous Si (a-Si) or a mixing
      of microcrystalline Si (mc-Si) and a-Si. A thin Au layer was deposited above the
      grown Si films, which formed a Schottky junction. Two types of Schottky solar
      cells were prepared on a fully a-Si film and a mixing of mc-Si and a-Si film.
      Under one sun illumination, the mixing of mc-Si and a-Si device provided 35% and
      68.4% enhancement in the open circuit voltage and fill factor compared to that of
      the amorphous device.

PMID- 22629960
TI  - Nanoporous Ti-metal film deposition using radio frequency magnetron sputtering
      technique for photovoltaic application.
AB  - Nanoporous Ti-metal film electrode was fabricated by radio frequency (rf)
      magnetron sputtering technique on nanoporous TiO2 layer prepared by sol-gel
      combustion method and investigated with respect to its photo-anode properties of
      TCO-less DSCs. The porous Ti layer (approximately 1 microm) with low sheet
      resistance (approximately 17 Omega/sq.) can collect electrons from the TiO2 layer
      and allows the ionic diffusion of I(-)/I(3-) through the hole. The porous Ti
      layer with highly ordered columnar structure prepared by 8 mTorr sputtering shows
      the good impedance characteristics. The efficiency of prepared TCO-less DSCs
      sample is about 4.83% (ff: 0.6, Voc: 0.65 V, Jsc: 11.2 mA/cm2).

PMID- 22629961
TI  - Effect of ammonia water on the morphology of monoethanolamine-assisted
      sonochemicaly synthesized ZnO nanostructures.
AB  - In the present work, ZnO nanostructures were synthesized by monoethanolamine
      (MEA)-assisted ultrasonic method at low temperature. Structural analysis was
      carried out by X-ray diffraction (XRD) confirmed the formation of hexagonal
      wurtzite structure of ZnO. The effect of ammonia water on the molecular structure
      of MEA, and its effect on the morphology of ZnO nanostructures were monitored by
      electron microscopy. Scanning electron microscopy (SEM) results suggest that ZnO
      nanoparticles with 100 nm in diameter were produced in case of MEA-assisted
      ultrasonic method. However, as ammonia water was added into the reaction system
      the morphology of ZnO nanoparticles changed into nanorods, flower-like
      nanostructures and finally microrods. Transmission electron microscopy (TEM) and
      selected area electron diffraction (SAED) studies showed that as prepared ZnO
      nanostructures were single crystalline in nature and grew in different directions
      resulted in the formation of various structures. The growth mechanism of as
      prepared ZnO nanostructures was discussed in detail. It was proposed that the
      addition of ammonia water into the reaction system resulted into the formation of
      ethylene diamine (EDA) which directed the growth of ZnO. The optical property was
      studied by photoluminescence (PL) spectroscopy showed only UV emission and no
      defects mediated visible emission.

PMID- 22629962
TI  - Structural and magnetic properties of Zn1-xcoxO nanorods prepared by microwave
      irradiation technique.
AB  - We have successfully synthesized large-scale aggregative flowerlike Zn1-xCo(x)O
      (0.0 < or = x < or = 0.07) nanostructures, consisting of many branches of
      nanorods at different orientations with diameter within 100-150 nm (tip diameter
      approximately 50 nm) and length of approximately 1 microm. The rods were prepared
      using Zinc nitrate, cobalt nitrate and KOH in 180 Watt microwave radiation for
      short time interval. The synthesized nanorods were characterized using X-ray
      diffraction (XRD), field emission scanning electron microscopy (FESEM), field
      emission transmission electron microscopy (FETEM) and DC magnetization
      measurements. XRD and TEM results indicate that the novel flowerlike
      nanostructures are hexagonal with wurtzite structure and Co ions were
      successfully incorporated into the lattice position of Zn ions in ZnO matrix. The
      selected area electron diffraction (SAED) pattern reveals that the nanorods are
      single crystal in nature and preferentially grow along [0 0 1] direction.
      Magnetic studies show that Zn1-xCo(x)O nanorods exhibit room temperature
      ferromagnetism. This novel nanostructure could be a promising candidate for a
      variety of future spintronic applications.

PMID- 22629963
TI  - Fabrication of TiO2/Tin-doped indium oxide-based photoelectrode coated with
      overlayer materials and its photoelectrochemical behavior.
AB  - The photoelectrochemical properties of TiO2-based photoelectrodes with metal
      oxide overlayers (e.g., ZnO, ZrO2, MgO, and Al2O3) were investigated. The metal
      oxides were deposited on TiO2/tin-doped indium oxide (ITO) films by spin-coating
      metal-alkoxide precursors. The formation of the overlayers was confirmed by
      energy dispersive X-ray spectroscopy (EDS) and high resolution transmission
      electron microscopy (HRTEM). Each overlayers were well-coated on the TiO2-based
      films and have approximately 2 nm thickness. The prepared films were used as
      photoanodes in a photoelectrochemical system with a Pt counter electrode to
      evaluate hydrogen production performance. Comparing with other overlayers, the
      ZnO-coated photoelectrode exhibits the highest rate of hydrogen evolution and
      which is better than the uncoated one. From the photoelectrochemical and
      spectroscopic study, the superior hydrogen production property of the ZnO-coated
      TiO2 photoelectrode was attributed to both the higher light absorbance of ZnO
      compared to TiO2 and the formation of hydroxyl groups at the ZnO surface.

PMID- 22629964
TI  - Consideration of bending and buckling behaviors of monolayer and multilayer
      graphene sheets.
AB  - Graphene is a two-dimensional carbon based material. Remarkable mechanical,
      thermal and electrical properties of graphene make it as promising material for
      advanced applications; nevertheless, majority of its mechanical properties are
      still unknown. This research investigates buckling and bending behaviors of
      monolayer and multilayer armchair and zigzag graphene sheets. Bending stiffness,
      critical buckling force per unit length and critical strain of graphene sheets
      have been measured by molecular dynamic simulation method. Zigzag graphene sheet
      shows higher bending stiffness than armchair sheet. Van der Waals interaction
      between graphene sheets has an improving effect on the stability of middle
      layers. Cross-linkages reduce the buckling force per unit length and the buckling
      strain of multi layer graphene sheets.

PMID- 22629965
TI  - Practical molecular dynamic simulation of monolayer graphene with consideration
      of structural defects.
AB  - Molecular dynamic simulation method has been employed to consider the mechanical
      properties of pristine and defected armchair and zigzag monolayer graphene sheets
      under tension and compression. Effects of Stone Wales (SW), Cell deformed (CD)
      and cell vacancy (CV) defects on ultimate stress and strain of graphene sheets
      have been considered. Obtained results indicate that zigzag graphene sheet has
      higher elastic modulus and stiffness than armchair type. Three SW defects have
      the highest destructive effect on ultimate stress and strain of zigzag graphene
      sheet while CV defect reveals the highest reducing effect on those of armchair
      type.

PMID- 22629966
TI  - The effects of graphene doping on the in-field Jc of MgB2 wires.
AB  - The field and temperature dependence of the critical current density Jct were
      measured for both un-doped and graphene doped MgB2/Fe wires manufactured by
      99.999% Crystalline Boron and 10% excess Magnesium (99%, 325 mesh). At 4.2 K and
      10 T, Jct was estimated to be for the wire sintered at 800 degrees C for 30
      minutes, the doped sample is almost improved as one order, compared with the best
      un-doped sample. At the same time, the temperature dependence of the upper
      critical field (Hc2) and the irreversibility field (Hirr) for the samples will
      also be included from the resistance (R)-temperature (T). A significant increase
      in the upper critical field is the main cause of the enhancement of the critical
      current density, Jct, in the high field region. The calculated active cross
      sectional area fraction (A(F)) represents the connectivity factor between
      adjacent grains. This value is decreased with wire samples, which is why the
      improvement of transport Jct is lower than the improvement of magnetic Jcm in
      diffusion bulk sample.

PMID- 22629967
TI  - Enhancement in the critical current density of C-doped MgB2 wire using a
      polyacrylic acid dopant.
AB  - C-doped MgB2 wires were fabricated from a polyacrylic acid (PAA) using a
      conventional in-situ PIT technique. The effects of the PAA content on the lattice
      parameter, microstructure, critical temperature (Tc) and critical current density
      (Jc) were examined. With increasing PAA content, the amount of MgO in the sample
      increased but the crystallinity, a-axis lattice parameter, and Tc of MgB2 wires
      decreased, indicating that the C that decomposed from PAA during heat treatment
      had substituted for B. All doped samples exhibited a higher Jc than the undoped
      sample at high magnetic field, and the Jc(B) property improved with increasing
      PAA content: for the 7 wt% doped sample, the Jc was approximately 3-times higher
      than that of the pristine sample (1.28 kA/cm2 vs. 3.43 kA/cm2) at 5 K and 6.6 T.
      The improved Jc(B) of the doped sample was attributed to the decreased grain
      size, enlarged lattice distortion and increased C doping level.

PMID- 22629968
TI  - Effects of reduced chemical vapor deposition environment on growth and optical
      characteristics of TiO2 nanobelts.
AB  - TiO2-delta nanobelts were self-catalytically grown at 510 degrees C on bare Si
      (100) substrates using metallorganic chemical vapor deposition. The nanobelt
      formation was critically affected by the partial pressure of oxygen. The
      nanobelts were grown when supplying only Ar or a mixed gas of Ar (90%) and H2
      (10%), while thin films were formed with an O2 gas flow of more than 50 cm3 min(
      1). The nanobelts consisted of approximately 20-30 nm size rutile-dominant
      nanocrystallites. A vapor-solid growth mechanism excluding a liquid phase
      appeared to control the nanobelt formation. The grown TiO2-delta nanobelts showed
      a strong photoluminescence (PL) spectra peak at approximately 550 nm due to
      oxygen vacancies. The nanobelt surface possessed significant amount of oxygen
      vacancies contributing PL and actively reacting with the environment, indicating
      promise for photocatalytic and gas sensor applications in a visible light regime.

PMID- 22629969
TI  - Low temperature growth and optical properties of ZnO nanowires using an aqueous
      solution method.
AB  - ZnO nanowires were grown on indium tin oxide (ITO) coated glass substrates at a
      low temperature of 90 degrees C using an aqueous solution method. The ZnO seeds
      were coated on the ITO thin films by using a spin coater. ZnO nanowires were
      formed in an aqueous solution containing zinc nitrate hexahydrate (Zn(NO3)2 x
      6H2O) and hexamethylenetetramine (C6H12N4). The pH value and concentration of the
      solution play an important role in the growth and morphologies of ZnO nanowires.
      The size of ZnO naonowires increased as the concentration of the solution
      increased. It was formed with a top surface of hexagonal and tapered shape at low
      and high pH values respectively. Additionally, the single crystalline structure
      and optical property of the ZnO nanowires were investigated using high-resolution
      transmission electron microscopy and photoluminescence spectroscopy.

PMID- 22629970
TI  - Synthesis and photocatalytic performance of titanium dioxide nanofibers and the
      fabrication of flexible composite films from nanofibers.
AB  - Titanium dioxide nanofibers were synthesized and applied in flexible composite
      films that are easy to handle and recycle after use. The nanofibers were obtained
      in a multi-step procedure. First, sodium titanate nanofibers were prepared from
      TiO2 nanoparticles through the alkali hydrothermal method. In the next step,
      sodium hydrogen titanate nanofibers were made by washing the sodium titanate
      nanofibers in HCl solution. Finally, the sodium hydrogen titanate nanofibers were
      transformed to TiO2 anatase nanofibers by calcination in air. The photocatalytic
      activity of TiO2 anatase nanofibers were evaluated and compared to a TiO2
      nanoparticle catalyst by decomposing methyl orange dye in aqueous solutions. The
      achieved reaction rate constant of TiO2 anatase nanofibers was comparable to that
      of Degussa P25. Paper-like flexible composite films were prepared by co
      filtrating aqueous dispersions of TiO2 catalyst materials and cellulose. The
      composite films made from the nanofibers exhibit better mechanical integrity than
      those of the nanoparticle-cellulose composites.

PMID- 22629971
TI  - Tin oxide-carbon nanotube composite for NOx sensing.
AB  - Tin oxide-single wall carbon nanotube (SWCNT) nano composites are synthesized for
      gas sensor application. The fabrication includes deposition of porous SWCNTs on
      thermally oxidized SiO2 substrates followed by rheotaxial growth of Sn and
      thermal oxidation at 300, 400, 500, and 600 degrees C in air. The effects of
      oxidation temperature on morphology, microstructure, and gas sensing properties
      are investigated for process optimization. The tin monoxide oxidized at 400
      degrees C showed the highest response at the operating temperature of 200 degrees
      C. Under the optimized test condition, the composite structure showed better
      response than both structures of SWCNTs and thin film SnO.

PMID- 22629972
TI  - Effect of hydrogen plasma pretreatment on the growth of silicon nanowires and
      their employment as the anode material of lithium secondary batteries.
AB  - Silicon nanowires were grown from a silane and argon gas mixture directly on a
      stainless steel substrate by radio-frequency plasma enhanced chemical vapor
      deposition (RF-PECVD) and used without any further treatment as the anode in the
      fabrication of lithium ion batteries. It was found that suitable pretreatment of
      the stainless steel substrate was required for the satisfactory growth of the
      silicon nanowires. In this study, the substrates were polished, etched in HF
      solution, coated with an aluminum catalyst layer with a thickness of c.a. 10 nm
      and then treated with a hydrogen plasma before the growth of the silicon
      nanowires. SEM (Scanning Electron Microscopy) and AFM (Atomic Force Microscopy)
      analyses showed that the grain size and surface roughness were increased after
      the hydrogen plasma pretreatment. The electrochemical performance of the silicon
      nanowires anode was also improved when the aluminum coated stainless steel
      substrate was exposed to the plasma for 20 min or longer; the initial coulombic
      efficiency was increased from 69.7% to 82% at a current density of 30 mA cm(-2).

PMID- 22629973
TI  - Tin-doped rutile titanium dioxide nanowires: luminescence, gas sensor, and field
      emission properties.
AB  - Sn-doped rutile TiO2 nanowires were synthesized by a thermal reactive evaporation
      route. Field emission scanning electron microscopy (FESEM) imaging reveals that
      the Sn-doped TiO2 nanowires exhibited diameters of 80-150 nm and 2-3 microns in
      length. High-resolution transmission electron microscopy (HRTEM) imaging makes it
      possible to observe that Sn-doped TiO2 nanowires show a certain lattices fringe
      of approximately 0.32 nm, which demonstrates that the nanowires are single
      crystalline with rutile structure and grow along the [110] axis.
      Cathodoluminescence (CL) reflected that on the surface of Sn-doped TiO2
      nanowires, many oxygen vacancies and defect states were formed during the crystal
      growth. These defect states raised a broad emission peak around the red-orange
      band. The ethanol sensing properties of Sn-doped rutile TiO2 nanowires at a
      temperature of 190 degrees C for the ethanol concentrations of 50, 100, 150, 200,
      400, 500, and 600 ppm, correspond to the sensor' sensitivity of 7, 12, 18, 19,
      23, and 26%, respectively. The sensitivity increased with an increase in the
      ethanol concentration. As-synthesized TiO2 nanowires revealed a turn-on field,
      approximately 5.1 V/microm, at a current density of 1 microAcm(-2).

PMID- 22629974
TI  - Microstructures and magnetic anisotropy of single-layered Fe-Pt alloy films by in
      situ annealing.
AB  - The single-layered Fe-Pt films with thickness of 30 nm are in-situ deposited
      directly on Si substrate at various substrate temperatures (Ts) of 350 to 590
      degrees C. As the Fe-Pt film is sputtered at substrate temperature is 350 degrees
      C, it shows (111) preferred orientation and tends to in-plane magnetic
      anisotropy. The L1(0) Fe-Pt film with (001) texture is obtained and exhibited
      perpendicular magnetic anisotropy as the substrate temperature is increased to
      470 degrees C. The perpendicular coercivity (Hc perpendicular), saturation
      magnetization (Ms) and perpendicular squareness (S perpendicular) of this film
      are 6.9 kOe, 674 emu/cm3 and 0.89, respectively, which reveal its significant
      potential as perpendicular magnetic recording media.

PMID- 22629975
TI  - Investigation of bonding characteristics between Si quantum dots and a SiO2
      matrix.
AB  - In order to understand and control the properties of Si quantum dot (QD)
      superlattice structures (SLS), it is necessary to investigate the bonding between
      the dots and their matrix and also the structures' crystallinities. In this
      study, a SiOx matrix system was investigated and analyzed for potential use as an
      all-silicon multi-junction solar cell. Si QD SLS were prepared by alternating
      deposition of Si rich SiOx (x = 0.8) and SiO2 layers using RF magnetron co
      sputtering and subsequent annealing at temperatures between 800 and 1,100 degrees
      C under nitrogen ambient. Annealing temperatures and times affected the formation
      of Si QDs in the SRO film. Raman and FTIR spectra revealed that nanocrystalline
      Si QDs started to precipitate after annealing at 1,100 degrees C for 1 hour. TEM
      images clearly showed SRO/SiO2 SLS and Si QDs formation in SRO layers after
      annealing at 1,100 degrees C for 2 hours. XPS analysis showed that Si-Si and Si-O
      bonding changes occurred above 1,100 degrees C. XPS analysis also revealed that
      Si QD SLSs started stabilizing after 2 hours' annealing and approached completion
      after 3 hours'. The systematic investigation of Si QDs in SiO2 matrices and their
      properties for solar cell application are presented.

PMID- 22629976
TI  - Crystallization behavior of silicon quantum dots in a silicon nitride matrix.
AB  - Silicon quantum dot superlattice was fabricated by alternating deposition of
      silicon rich nitride (SRN) and Si3N4 layers using RF magnetron co-sputtering.
      Samples were then annealed at temperatures between 800 and 1,100 degrees C and
      characterized by grazing incident X-ray diffraction (GIXRD), transmission
      electron microscopy (TEM), Raman spectroscopy, and Fourier transform infrared
      spectroscopy (FTIR). GIXRD and Raman analyses show that the formation of silicon
      quantum dots occurs with annealing above 1,100 degrees C for at least 60 minutes.
      As the annealing time increased the crystallization of silicon quantum dots was
      also increased. TEM images clearly showed SRN/Si3N4 superlattice structure and
      silicon quantum dots formation in SRN layers after annealing at 1,100 degrees C
      for more than 60 minutes. The changes in FTIR transmission spectra observed with
      annealing condition corresponded to the configuration of Si-N bonds.
      Crystallization of silicon quantum dots in a silicon nitride matrix started
      stabilizing after 60 minutes' annealing and approached completion after 120
      minutes'. The systematic investigation of silicon quantum dots in a silicon
      nitride matrix and their properties for solar cell application are presented.

PMID- 22629977
TI  - Preparation of silica thin films by novel wet process and study of their optical
      properties.
AB  - Silicon dioxide (SiO2) thin films have gained considerable attention because of
      their various industrial applications. For example, SiO2 thin films are used in
      superhydrophilic self-cleaning surface glass, UV protection films, anti
      reflection coatings, and insulating materials. Recently, many processes such as
      vacuum evaporation, sputtering, chemical vapor deposition, and spin coating have
      been widely applied to prepare thin films of functionally graded materials.
      However, these processes suffer from several engineering problems. For example, a
      special apparatus is required for the deposition of films, and conventional wet
      processes are not suitable for coating the surfaces of substrates with a large
      surface area and complex morphology. In this study, we investigated the film
      morphology and optical properties of SiO2 films prepared by a novel technique,
      namely, liquid phase deposition (LPD). Images of the SiO2 films were obtained by
      scanning electron microscopy (SEM) and atomic force microscopy (AFM) in order to
      study the surface morphology of these films: these images indicate that films
      deposited with different reaction times were uniform and dense and were composed
      of pure silica. Optical properties such as refractive index and transmittance
      were estimated by UV-vis spectroscopy and ellipsometry. SiO2 films with porous
      structures at the nanometer scale (100-250 nm) were successfully produced by LPD.
      The deposited film had excellent transmittance in the visible wavelength region.

PMID- 22629978
TI  - A novel method for patterning of poly(3,4-ethylenedioxythiophene) films using UV
      exposure-activated self-assembled monolayers.
AB  - We have investigated a novel method for patterning of (3, 4
      ethylenedioxythiophene) PEDOT, which has involved a selective polymerization of
      PEDOT on an UV-activated Self-Assembled-Monolayer surface. OTS coated surface has
      been activated by UV exposure, and the UV-exposed area served as adsorption sites
      for FeCl3 oxidants, providing a selective deposition of PEDOT films on FeCl3
      adsorbed area, and thus leading to the selective patterning of PEDOT films. UV
      irradiation time and mask pattern dimension are main contributors to
      patternability: UV irradiation through Cr-mask (3 microm design) lead to
      approximately 3-5 microm patterns of PEDOT films, depending on the UV exposure
      time. In addition, a scotch tape peel test revealed excellent adhesion property
      of PEDOT to SiO2. Consequently, this simple method can be applied to define deep
      submicron dimensions due to its ability of providing a direct transfer of mask
      patterns to the substrate.

PMID- 22629979
TI  - Structures and properties of poly(3-alkylthiophene) thin-films fabricated though
      vapor-phase polymerization.
AB  - Organic semiconducting polymer thin-films of 3-hexylthiophene, 3-octylthiophene,
      3-decylthiophene, containing highly oriented crystal were fabricated by gas-phase
      polymerization using the CVD technique. These poly(3-alkylthiophene) films had a
      crystallinity up to 80%, and possessed a Hall mobility up to 10 cm2/Vs. The
      degree of crystalinity and the mobility values increased as the alkyl chain
      length increased. The crystal structure of the polymers was composed of stacked
      layers constructed by a side-by-side arrangement of alkyl chains and in-plane pi
      pi stacking. These thin films are capable of being applied to organic electronics
      as the active materials used in thin-film transistors and organic photovoltaic
      cells.

PMID- 22629980
TI  - Effects of Pt junction on electrical transport of individual ZnO nanorod device
      fabricated by focused ion beam.
AB  - The electrical transport of individual ZnO nanorod devices manufactured by
      focused ion beam (FIB) was investigated by the direct measurement of electrical
      resistance at electrode junctions of cross-sectioned devices using two
      nanoprobes. The cathodoluminescence (CL) measurements were also performed to
      evaluate the crystallinity at the center and edge of the cross-sectioned ZnO
      nanorods. The electrical transport of the individual ZnO nanorod device depends
      strongly on the crystallinity of the ZnO nanorod itself and the carbon contents
      at Pt junctions. The ZnO-Au junction of the device acted as the fastest path for
      electrical transport.

PMID- 22629981
TI  - High-resolution patterning of silver thin films with a water-mediated metal
      transfer printing.
AB  - We report a direct printing method, water-mediated metal transfer printing (mTP),
      for generating Ag patterns with a wide range of feature sizes. Water-mediated mTP
      is based on the direct transfer of a metal thin film from a stamp to a substrate
      via a water-mediated surface bonding. An Ag thin film is used as a solid "ink" in
      the mTP, which can be used for the formation of micro- and nanoscale Ag
      structures. To demonstrate its usefulness, we used the water-mediated mTP to
      fabricate low voltage ZnO thin-film transistors.

PMID- 22629982
TI  - The effects of nitrogen bonding on hardness of AIN/CrN multilayer hard coatings.
AB  - AIN/CrN multilayer hard coatings with various bilayer thicknesses were fabricated
      by a reactive sputtering process. The microstructural and mechanical
      characterizations of multilayer coatings were investigated through transmission
      electron microscope (TEM) observations and the hardness measurements by nano
      indentation. In particular, the variation of chemical bonding states of the
      bilayer nitrides was elucidated by near edge X-ray absorption fine structure
      (NEXAFS) spectroscopy. Many broken nitrogen bonds were formed by decreasing the
      bilayer thickness of AIN/CrN multilayer coatings. Existence of optimum AIN/CrN
      multilayer coatings thickness for maximum hardness could be explained by the
      competition of softening by the formation of broken nitrogen bonds and
      strengthening induced by decreasing bilayer thickness.

PMID- 22629983
TI  - Self-assembled growth of GaAs anti quantum dots in InAs matrix by migration
      enhanced molecular beam epitaxy.
AB  - Self-assembled GaAs anti quantum dots (AQDs) were grown in an InAs matrix via
      migration enhanced molecular beam epitaxy. The transmission electron microscopy
      image showed that the 2D to 3D transition thickness is below 1.5 monolayers (MLs)
      of GaAs coverage. The average diameter and height of the GaAs AQDs for 1.5 ML
      GaAs coverage taken from the atomic force microscopy image were approximately
      29.0 nm and 1.4 nm, respectively. The density was approximately 6.0 x 10(10) cm(
      2). The size of the AQDs was enlarged in the InAs matrix compared with that on
      the surface. These results indicate that the GaAs AQDs in the InAs matrix under
      tensile strain can be effectively formed with the assistance of the migration
      enhanced epitaxy method.

PMID- 22629984
TI  - Selective area atomic layer deposited ZnO nanodot on self-assembled monolayer
      pattern using a diblock copolymer nano-template.
AB  - ZnO nanodots were prepared by selective area atomic layer deposition (SA-ALD) on
      an octadecyltrichlorosilane (ODTS) self-assembly monolayers (SAMs) patterns
      formed using a diblock co-polymer (DBC) nanotemplate. In order to transfer well
      ordered nanaotemplate in SAMs, SiO2 sacrificial layer was inserted between DBC
      and SAMs. Cylindrical nanoholes under 16 nm diameters were well-formed on SiO2
      layer. SA-ALD of ZnO was successfully performed on by ODTS SAMs.

PMID- 22629985
TI  - SPICE macromodel and CMOS emulator for memristors.
AB  - In this paper, a new SPICE macromodel and CMOS emulator for memristors are
      proposed and verified to fit to the memristor's model equation very well in the
      entire range of memristor's resistance from the RESET state to the SET state.
      Compared with the memristor's model equation, average percentage errors in the
      new SPICE macromodel and in the 4-bit CMOS emulator are less than 0.5% and 0.9%,
      respectively. In addition, the CMOS emulator for memristors which can be
      implemented by a CMOS circuit will be very useful to design and verify various
      peripheral circuits for memristor applications particularly when the memristor
      fabrication process is not ready.

PMID- 22629986
TI  - Suppressed recombination in quantum dot-sensitized solar cells with blocking
      layers on FTO substrates.
AB  - The compact and thin TiO2 blocking layers (c-TiO2) were formed on F-doped SnO2
      (FTO) substrate in quantum dots-sensitized solar cells (QSSCs) by chemical
      deposition. The c-TiO2 layers induced indirect contact between electrolyte and
      FTO electrode, which reduced leakage in QSSCs. The QSSCs showed power conversion
      efficiency (Eff) of 3.85% in the presence of c-TiO2 layers which leads to 21%
      improved compared to that without c-TiO2 layers (Eff = 3.18%). The presence of
      the c-TiO2 layers in QSSCs also improved the stability under illumination.

PMID- 22629987
TI  - Solvent dependent triphenylamine based D-(pi-A)n type dye molecules and optical
      properties.
AB  - D-(pi-A)n type dyes of triphenylamine derivatives were synthesized and their
      absorption and luminescence in different solvents were examined to investigate
      solvent dependent properties observed for their emissions in solvents with
      different dielectric constants. The emission wavelengths showed a dramatic blue
      shift with increasing solvent polarity. The results of molecular orbital
      calculations by computer simulation, based on Material Studio suite of programs,
      were found to reasonably account for the spectral properties. Relative levels of
      HOMO and LUMO were measured and calculated and all derivatives exhibited strong
      solid fluorescence with distinctively different FWHMs.

PMID- 22629988
TI  - A colorimetric and fluorescent chemosensor for Ni2+ based on donor-pi-acceptor
      charge transfer dye containing 2-cyanomethylene-3-cyano-4,5,5-trimethyl-2,5
      dihydrofuran acceptor and 4-bis(pyridin-2-ylmethyl)aminobenzene donor.
AB  - A new designed colorimetric and fluorescent dye chemosensor was synthesized,
      characterized and computationally calculated using MO theory calculation, which
      was based on donor-pi-acceptor electron charge transfer system. This particularly
      designed dye chemosensor displayed the selective Ni2+ ion chemo-sensing effects
      in optical properties with absorption and fluorescence emission. This dye
      chemosensor represented clear absorption spectra changes with Ni2+ ion and the
      dramatic fluorescence quenching effect with Ni2+ ion was determined. However it
      showed no significant optical spectra changes upon the addition of other metal
      ions such as Cd2+, Na2+, Mg2+, Pb2+, Fe2+, Fe3+, Ca2+, Cu2+, Hg2+, except Zn2+.

PMID- 22629989
TI  - Influence of various plasma treatment on the properties of carbon nanotubes for
      composite applications.
AB  - In present work, the effects of hydrogen and oxygen plasma treatments on the
      structural properties of carbon nanotubes (CNTs) synthesized by catalytic CVD
      (Chemical Vapor Deposition) have been systematically investigated. Field emission
      scanning electron microscopy (FE-SEM), high-resolution transmission electron
      microscopy (HRTEM), and Raman spectroscopy were used to characterize the
      microstructural changes of the CNTs. The oxygen plasma treatment resulted in that
      the nanoparticles were appeared at the surface of CNTs. At high r.f. power (300
      Watt), the microstructure of CNT was changed from nanotube type to nano
      particles. Long plasma treatment time changed the CNT morphology dramatically.
      For hydrogen plasma, however, there was no change in microstructure of CNT From
      the Raman analysis, the crystallinity of CNT was deteriorated by the plasma
      treatment, regardless of plasma power, treatment time, and gas types. The CNTs
      treated in oxygen plasma for 90 min showed excellent dispersion properties in
      aqueous solution.

PMID- 22629990
TI  - Effect of plasma treatments to graphite nanofibers supports on electrochemical
      behaviors of metal catalyst electrodes.
AB  - In the present work, we had studied the graphite nanofibers as catalyst supports
      after a plasma treatment for studying the effect of surface modification. By
      controlling the plasma intensity, a surface functional group concentration was
      changed. The nanoparticle size, loading efficiency, and catalytic activity were
      studied, after Pt-Ru deposition by a chemical reduction. Pt-Ru catalysts
      deposited on the plasma-treated GNFs showed the smaller size, 3.58 nm than the
      pristine GNFs. The catalyst loading contents were enhanced with plasma power and
      duration time increase, meaning an enhanced catalyst deposition efficiency.
      Accordingly, cyclic voltammetry result showed that the specific current density
      was increased proportionally till 200 W and then the value was decreased.
      Enhanced activity of 40 (mA mg(-1)-catalyst) was accomplished at 200 W and 180
      sec duration time. Consequently, it was found that the improved electroactivity
      was originated from the change of size or morphology of catalysts by controlling
      the plasma intensity.

PMID- 22629991
TI  - Single-walled carbon nanotubes based chemicapacitive sensors.
AB  - Carboxylated single-walled carbon nanotubes (SWNTs) based chemicapacitive gas
      sensors were fabricated by AC dielectrophoretically aligning SWNTs across
      microfabricated gold electrodes with controlled density/device resistance. Two
      different sensing configurations (i.e., horizontal/in-plane and vertical/out-of
      plane) were utilized to compare their sensing performance. Upon exposure to water
      vapor at room temperature, the response (R = [(C--C0)/C0] x 100%) increased with
      an increase in water vapor concentration similar to that of resistance response.
      In horizontal configuration, the response was increased with an increase in
      device resistance which might be attributed to preferentially alignment of
      semiconducting SWNTs during initial phase of alignment. However, the response was
      independent of device resistance in vertical/out-of-plane configuration which
      indicated that the sensing mechanism is based on the change of dielectric
      constant of gate and atmosphere.

PMID- 22629992
TI  - ZnO nanorods, nanotubes and nanorings: controlled synthesis and structural
      properties.
AB  - Controlled synthesis of ZnO nanorods (ZNRDs), nanotubes (ZNTs) and nanorings
      (ZNRs) has been carried out by a two-step sonochemical/chemical process at room
      temperature without any catalyst, template or seed layer. The crystallinity,
      structure and morphology of ZNRDs, ZNRs and ZNTs were examined by X-ray
      diffraction (XRD) analysis, scanning electron micrographs (SEM), high resolution
      transmission electron microscope (HR-TEM) and selected area electron diffraction
      (SAED). The as-prepared ZnO nanostructures were single crystalline with hexagonal
      cross-section and uniform size. The effect of precursor concentration on the
      growth and that of the etching duration on the hollow formation were analyzed,
      and the obtained results revealed that the precursor concentration and etching
      time play an important role in determining final morphologies of the samples. By
      tuning the etching time, the precise size control of ZNTs and ZNRs was achieved.
      Possible formation mechanisms of these nanostructures are proposed based on the
      experimental results.

PMID- 22629993
TI  - Improvement in sensing properties of SnO2 nanowires by functionalizing with Pt
      nanodots synthesized by gamma-ray radiolysis.
AB  - Selectively-grown networked SnO2 nanowires were functionalized with Pt nanodots
      by the radiolysis process. NO2 sensing characteristics of Pt-functionalized SnO2
      nanowires were compared with those of bare SnO2 nanowires. The results
      demonstrate that the Pt functionalization greatly enhances the sensitivity and
      response time in SnO2 nanowire-based gas sensors. The enhancement is likely to be
      associated with the spillover effect and/or easy dissociation of NO2 into more
      active chemical species by the catalytic effect of Pt.

PMID- 22629994
TI  - Fabrication of Ni compound nanocrystal/nanocarbon composites by cooling of
      chloride-based fluxes.
AB  - Unique Ni compound nanocrystals were successfully grown on carbon nanotubes
      (CNTs) by cooling a mixed chloride flux. Cup-stacked CNTs (CSCNTs) were used as
      the nanocarbon materials because of their structural features. The grown
      nanocrystals had a nanosheet structure, which was densely assembled and had a
      ribbon-like morphology. Therefore, the nanocrystal/CSCNT composites were expected
      to have a highly active surface area for the catalyst composites. The selected
      area electron diffraction pattern and the related radial intensity profiles
      indicated that the grown nanocrystals were Ni(OH)2. When the pristine CSCNTs were
      used as a starting material, the formation efficiency of the nanocrystal/CSCNT
      composites decreased because the pristine CSCNTs were not dispersed in the KCl
      LiCl flux. Therefore, functionalization of the CSCNTs was carried out with VUV
      light irradiation. The dispersibility of the VUV light-treated CSCNTs increased
      in the KCl-LiCl flux in comparison with the pristine CSCNTs because oxygen
      containing functional groups, such as -COOH and -CO, were introduced onto the
      surfaces of the CSCNTs.

PMID- 22629995
TI  - Effect of a fullerene derivative on the performance of TiO2-nanotube-based dye
      sensitized solar cells.
AB  - Highly ordered TiO2 nanotube arrays were prepared by anodic oxidation of Ti foil
      in an application to dye-sensitized solar cells (DSCs). A fullerene derivative
      called PC61BM was used as a material for the surface modification of TiO2
      nanotube arrays to improve the power conversion efficiency of DSCs Although open
      circuit voltages (Voc) were slightly decreased by PC61BM interlayer, short
      circuit current densities (Jsc) were increased and thus the power conversion
      efficiencies were improved. EIS (Electrochemical Impedance Spectroscopy) results
      showed superior properties for PC61BM-coated samples.

PMID- 22629996
TI  - Size and morphology controlled lithium manganese oxide on silica sphere with core
      shell structure.
AB  - Core-shell structures were prepared from synthesized SiO2-LiMn2O4 with manganese
      oxide as shell on the silica core by a precipitation method, which allowed
      control of core structure in terms of thickness and particle size. X-ray
      diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), field
      emission-transmission electron microscopy (FE-TEM), and energy dispersive
      spectroscopy (EDS) were used to characterize the SiO2-LiMn2O4. According to FE
      SEM images, particle growth was controlled by controlling the amount of manganese
      precursor and the temperature. The synthesized core-shell structure was composed
      of silica, lithium silicate, Mn2O3, and the spinel phase of lithium manganese
      oxide. Electrochemical measurements show that the synthesized core-shell
      structure has poorer electrochemical performance than that of LiMn2O4.

PMID- 22629997
TI  - The effects of reaction factors on the fabrication of nano-sized indium tin oxide
      powder by spray pyrolysis process.
AB  - In this study, waste ITO target is dissolved into hydrochloric acid to generate a
      complex acid solution. Nano-sized ITO powder with the average particle size below
      50 nm is generated from this complex solution by spray pyrolysis process. This
      study also examines the influences of reaction parameters such as nozzle tip size
      and air pressure on the properties of the generated ITO powder. When the nozzle
      tip size is at 1 mm, the particle size distribution becomes more uniform in
      contrast to the case of other tip sizes, and the average particle size is around
      50 nm. When the nozzle tip size increases up to 5 mm, the average particle size
      increases slightly, yet the particle size distribution becomes extremely
      irregular. Along with the change of nozzle tip size, the changing tendencies of
      XRD peak intensity and specific surface area are almost consistent with that of
      average particle size. Along with the increase of air pressure, the average
      particle size of the ITO powder gradually decreases, and the particle size
      distribution becomes more uniform. When the air pressure is at 0.1 kg/cm2, the
      particle size distribution appears extremely irregular, yet the average particle
      size is around 70 nm. When the air pressure is at 3 kg/cm2, the average particle
      size decreases down to 40 nm. Along with the increase of air pressure, the XRD
      peak intensity gradually decreases and the specific surface area increases.

PMID- 22629998
TI  - Growth of high quality ZnO nanowires on graphene.
AB  - We report growth of the ZnO nanowires on graphene/SiO2/Si substrates using a
      chemical vapor deposition method. The length of nanowires varies from 1 microm to
      10 microm with increasing the growth time from 30 min to 90 min. X-ray
      diffraction and high-resolution transmission electron microscopy investigations
      predict the high structural quality of the c-axis grown single crystalline ZnO
      nanowires. Temperature dependent photoluminescence spectra from the nanowires
      reveal excellent optical quality and excitonic behavior in the single crystalline
      ZnO nanowires. A well-resolved free exciton emission at 3.375 eV, indicates high
      crystalline quality nanowires and a strong PL peak at 3.370 eV is assigned to
      neutral-donor bound excitons (D0X).

PMID- 22629999
TI  - One step synthesis of rutile TiO2 nanoparticles at low temperature.
AB  - Sphere-like rutile TiO2 nanocrystals have been synthesized by sol-gel method
      followed by hydrolysis of titanium tetrachloride in deionized water in the
      presence of ammonium hydroxide as hydrolysis catalyst. The as-prepared TiO2
      nanoparticles have single rutile phase with average diameter approximately 26.4
      nm. The results show that the temperature has a great influence on the particle
      size distribution and also crystalline phase (rutile) of TiO2 nanoparticles is
      consistent with the temperature. Characterization of the as-prepared
      nanocrystalline powder was carried out by different techniques such as powder X
      ray diffraction (XRD), field emission transmission electron microscopy (FE-TEM)
      and Raman spectroscopy.

PMID- 22630000
TI  - Rutile structured SnO2 nanowires synthesized with metal catalyst by thermal
      evaporation method.
AB  - One-dimensional (1-D) nanostructures such as tubes, rods, wires, and belts have
      attracted considerable research activities owing to their strong application
      potential as components for nanosize electronic or optoelectronic devices
      utilizing superior optical and electrical properties. Characterizing the
      mechanical properties of nanostructure is of great importance for their
      applications in electronics, optoelectronics, sensors, actuators. Wide-bandgap
      SnO2 semiconducting material (Eg = 3.6 eV at room temperature) is one of the
      attractive candidates for optoelectronic devices operating at room temperature,
      gas sensors, and transparent conducting electrodes. The synthesis and gas sensing
      properties of semiconducting SnO2 nanomaterials have became one of important
      research issues since the first synthesis of SnO2 nanobelts. Considering the
      important application of SnO2 in sensors, these structures are not only ideal
      systems for fundamental understanding at the nanoscale level, but they also have
      potential applications as nanoscale sensors, resonator, and transducers. The
      structured SnO2 nanorods have been grown on silicon substrates with Au catalytic
      layer by thermal evporation process over 800 degrees C. The resulting sample is
      characterized and analyzed by X-ray diffraction (XRD), field emission scanning
      electron microscope (FE-SEM), transmission electron microscopy (TEM), high
      resolution transmission electron microscopy (HRTEM), and energy-dispersive X-ray
      spectroscopy (EDS). The morphology and structural properties of SnO2 nanowires
      were measured by scanning electron microscopy and high-resolution transmission
      electron microscopy. The mean diameter of the SnO2 nanorods grown on Au coated
      silicon (100) substrate is approximately 80 nm. In addition, X-ray diffraction
      measurements show that SnO2 nanorods have a rutile structure. The formation of
      SnO2 nanowires has been attributed to the vapor-liquid-solid (VLS) growth
      mechanisms depending on the processing conditions. We investigated the growth
      behavior of the SnO2 nanowires by variation of the growth conditions such as gas
      partial pressure and temperature.

PMID- 22630001
TI  - Synthesization and characterization of FeS2 by mechanical alloying for Na/FeS2
      cell.
AB  - In this study, the FeS2 fine compound powders were synthesized by mechanical
      alloying (MA) for 15 hrs and stearic acid was added as PCA (Process Control
      Agent) to prevent the excessive cold welding and agglomeration. For the purpose
      of ulteriorly reducing the particle size to improve the contact areas between the
      active materials and conducting agents, the wet ball milling process was applied
      by employing normal hexane (C6H14) as the milling solvent. The mean particle size
      of FeS2 powders about 1.14 microm were obtained after 24 hrs wet ball milling.
      The powders were characterized by FE-SEM, XRD, TEM and EDS. To compare the
      influence of particle size on the properties of charge/discharge, the same
      electrolyte was employed for both tests by dissolving 1M NaCF3SO3 (sodium
      trifluoromethanesulfonate) in a liquid of TEGDME (tetraethylene glycol
      dimethylether). The first discharge capacity of Na/FeS2 cell made by dry ball
      milled powders was 440 mAh/g with a plateau potential at approximately 1.25 V
      versus Na/Na+ and 260 mAh/g at the 25th cycle at room temperature. Meanwhile, the
      initial discharge capacity of Na/FeS2 cell made by wet ball milled powders was
      614 mAh/g with the same discharge plateau potential and retained 385 mAh/g at the
      25th cycle. And the discharge capacity for wet milled system decreased
      continuously by repeated charge/discharge cycling in the first 20 cycles and has
      little change after 60 cycles, which means the good cycling properties, remaining
      half of its initial discharge capacity of 320 mAh/g even after 100 cycles.

PMID- 22630002
TI  - Conformational-induced doping effect of sodium dodecyl benzene sulfonate on
      single walled carbon nanotubes.
AB  - The doping behavior of single-walled carbon nanotubes (SWCNTs) was investigated
      with an emphasis on the control of the conformation of sodium dodecylbenzene
      sulfonate (NaDDBS) with sulfonate groups acting as an electro-withdrawing group.
      The conformation of adsorbed NaDDBS on SWCNTs was controlled as a function of the
      amount of NaDDBS. The doping behavior of SWCNTs was significantly affected by the
      dosing amount of NaDDBS due to the conformational change of NaDDBS adsorbed on
      the SWCNT surface, which affected the spatial distance between the SWCNT surface
      and the sulfonate groups in NaDDBS. At a higher concentration, the spatial
      distance between the sulfonate group in NaDDBS and SWCNT was not sufficiently
      close enough to dope SWCNT due to the repulsive forces between the sulfonate
      groups in NaDDBS. Alternatively, at a lower concentration, NaDDBS acted as a p
      type dopant for SWCNTs. To this end, this paper demonstrates a new tendency of
      doping that is related to the adsorbed behavior of a dispersant.

PMID- 22630003
TI  - Magnetic anisotropy and morphology of Fe epitaxial layers grown on MgO/InAs
      heterostructures.
AB  - In-plane magnetic anisotropy and the corresponding morphology of Fe epitaxial
      layers have been investigated with respect to underlying MgO growth temperature
      when epitaxial Fe/MgO layers are grown on InAs (001) substrates. Coexistence of
      three-dimensional Fe islands with strong in-plane textures along <110> and (100)
      is observed on 4 nm thick MgO layers grown on 200 degrees C, leading to the
      absence of magnetic anisotropy. Meanwhile, the partially relaxed MgO layers grown
      above 300 degrees C give rise to two-dimensional Fe layers with cubic magnetic
      anisotropy. The higher MgO growth temperature accelerates the two-dimensional
      layer formation of the subsequent Fe as well as the advent of cubic anisotropy by
      reducing underlying strain within the MgO layer.

PMID- 22630004
TI  - Fabrication and characterization of thermoelectric thick film prepared from p
      type bismuth telluride nanopowders.
AB  - In this study, bismuth telluride (Bi2Te3)-based nanopowders with particle size
      ranging from 100 to 300 nm are prepared by high-energy ball milling. Then, the
      prepared nanopowders are homogeneously mixed with organic binders to form a
      paste; this paste is used as the raw material to prepare thick-film
      thermoelectric modules. The thick film prepared by screen printing followed by
      hot pressing of p-type pastes show reproducible thermoelectric properties,
      exhibiting an electrical resistivity of 2.0 m Omega cm and a Seebeck coefficient
      of 298 muVK-1. The prepared p-type Bi2Te3 thick film has a high power factor
      because its Seebeck coefficient is significantly higher than that of Bi2Te3 based
      bulk materials. These results indicate that a thick film prepared from bismuth
      telluride nanopowders has potential for use as high-performance thermoelectric
      modules in practical applications such as power generation and cooling system in
      electronic devices.

PMID- 22630005
TI  - Hardness and nitrogen bonding structure of AlxTi1-xN/CrN multilayer hard coating.
AB  - AlxTi1-xN/CrN multilayer coatings were fabricated by magnetron sputtering and
      those hardness variations were studied by observing the crack propagation and
      measuring the chemical bonding state of nitrides by Ti addition. While AlN/CrN
      multilayer shown stair-like crack propagation, AlxTi1-xN/CrN multilayer
      illustrated straight crack propagation. Most interestingly, Ti addition induced
      more broken nitrogen bonds in the nitride multilayers, leading to the reduction
      of hardness. However, the hardness of Al0.25Ti0.75N/CrN multilayer, having high
      Ti contents, increased by the formation of many Ti-N bond again instead of Al-N
      bond. From these results, we found that linear crack propagation behavior was
      dominated by broken nitrogen bonds in the AlxTi1-xN/CrN multilayer coatings.

PMID- 22630006
TI  - Properties of flexible phosphorescence polymer light emitting diodes coated on
      polyethylenenaphthalate plastic substrates.
AB  - Flexible phosphorescence polymer light emitting diodes (PhPLEDs) with
      PEN/ITO/PEDOT:PSS/ PVK:Ir(ppy)3/TPBI/LiF/Al structure were fabricated to
      investigate the effects of Ir(ppy)3 doping concentrations on the optical and
      electrical properties of the devices. PVK and Ir(ppy)3 conjugated polymers as
      host and guest materials in the emission layer were spun coated at various
      concentrations of Ir(ppy)3 ranging from 2.0 to 8.0 vol%. As the concentration of
      Ir(ppy)3 increased from 2.0 to 6.0 vol%, the electrical and optical properties of
      the flexible PhPLEDs were improved clearly. Maximum luminance and current density
      were obtained for a PhPLED with an Ir(ppy)3 concentration of 6.0 vol%, with 6815
      cd/m2 and 393 mA/cm2 at 9 V. The current efficiency tends to increase with the
      Ir(ppy)3 concentration, because of the formation of the excitons required to emit
      light.

PMID- 22630007
TI  - Effects of process conditions on the properties of silicon nanoparticles
      synthesized by gas phase reactions using inductive coupled plasma.
AB  - Silicon nanoparticles were synthesized by passing monosilane through a quartz
      tube wrapped with Inductive Coupled Plasma (ICP) coil. Microstructures of
      synthesized silicon nanoparticles were investigated with various process
      conditions. To research the effects of process parameters on the properties of
      nanoparticles, we verified the partial pressure of monosilane, the plasma power
      and the working pressure. The highly crystalline silicon nanoparticles were only
      achieved at the proper partial pressure of the reactive gas and plasma power.
      Partial pressure determined not only the particle size but also the crystallinity
      of the nanoparticles. The plasma power was controlled from 50 to 100 W which
      determined not the particle size but the crystallinity of nanoparticles.
      Especially, too low a power resulted in amorphous particles with an average sizes
      of 5.25 nm. As the working pressure increased, the amount of produced
      nanoparticles linearly increased and the maximum production yield was at 76
      mg/hr. Controlling those parameters, we achieved monodispersed single crystalline
      silicon nanoparticles with an average diameter of 7.52 nm. Silicon nanoparticles
      in this study can be applied to light absorbing material for solar cells and the
      wavelength down-converter material of Light Emitting Diode (LED).

PMID- 22630008
TI  - Study on preparation of the core-nanoshell composite absorbers by high-energy
      ball milling at room temperature.
AB  - Electromagnetic (EM) wave pollution has become the chief physical pollution for
      environment. In recent years, some researches have been focused on the
      preparation of nano-composite absorbers at low temperatures or even at room
      temperature. In this letter, preparation of nanocomposite by using high-energy
      ball milling at room temperature is reported. The core-nanoshell composite
      absorbers with magnetic fly-ash hollow cenosphere (MFHC) as nuclear and
      nanocrystalline magnetic material as shell were prepared by high-energy ball
      milling and vacuum-sintering in this paper. The pre-treatment of MFHC, the
      sintering process and the mol ratio of starting chemicals had a significant
      impact for property of composite absorbers. The results of X-ray diffraction
      analysis (XRD), transmission electron microscope (TEM), vibrating sample
      magnetometer (VSM) and vector network analyzer (VNA) analysis indicated that
      perfect-crystalline nanomagnetic material coating was gotten with a particle size
      of 12 nm after ball milling. The results show the MFHC is dielectric loss and
      magnetic loss too; the exchange-coupling interaction happened between ferrite of
      the MFHC and nanocrystalline magnetic material coating. The exchange-coupling
      interaction enhances magnetic loss of composite absorbers. They have a perfect EM
      parameters at low microwave frequency. The core-nanoshell composite absorbers
      have a higher magnetic loss at low frequencies, and it is consistent with
      requirements of the microwave absorbing material at the low-frequency absorption.
      The microwave absorptivity of the core-nanoshell composite absorbers is better
      than single material.

PMID- 22630009
TI  - Effect of collector speed and flow rate on morphology of Er doped TiO2
      nanofibers.
AB  - The 0.5 mol% Er3+ doped TiO2 (Er(3+)-TiO2) nanofibers were synthesized by a sol
      gel derived electrospinning and subsequent calcination for 3 h at 500 degrees C
      in air. The calcined fibers were examined to evaluate the effect of collector
      speed and flow rate on morphology of the fibers. The dynamic viscosity and
      surface tension of precursor solution were 34 cP and 22.7 mN/m, respectively. The
      Er(3+)-TiO2 nanofibers were electrospun horizontally on the drum rotated at 100
      500 rpm and flow rate of 0.2-0.5 mL/h under a DC voltage of 10 kV. The grounded
      collector is a stainless mandrel placed 12 cm away from the tip of the needle.
      Beads were observed for the nanofibers prepared at flow rates from 0.2 mL/h to
      0.5 mL/h when the collector speed was 100 rpm. The nanofibers increased in
      diameter slightly from 150 nm to 190 nm as the flow rate was raised from 0.2 mLh
      to 0.5 mL/h. No beads were found at the collector speed of above 300 rpm when the
      flow rate was 0.2 mL/h. The optimized flow rate and collector speed of the
      nanofibers were determined to be in the range of 0.2-0.3 mL/h and 300-400 rpm,
      respectively. Uniform, smooth and continuous fibers with diameters of 150 to 170
      nm were detected. Crystallite size determined by the Scherrer formula was about 6
      nm. It can be concluded that the collector speed and the flow rate are
      influential on the morphology of the Er(3+)-TiO2 nanofibers. The Er(3+)-TiO2
      nanofibers, prepared at 0.2 mL/h and 300 rpm, had typical absorption peaks
      located at 490, 523 and 654 nm, corresponding to the transitions from 4I15/2 to
      4F7/2, 2H11/2 and 4F9/2, respectively. The Er(3+)-TiO2 nanofibers showed enhanced
      photoresponses under visible light.

PMID- 22630010
TI  - Fabrication of nanoporous TiO2 hollow capsules using core-shell silica
      nanoparticle templates.
AB  - We report on the fabrication of the nanoporous TiO2 hollow capsules using core
      shell silica nanoparticle templates. The thickness of the capsules can be simply
      controlled by varying the amount of the TiO2 precursor. The resulting nanoporous
      capsules exhibited the high specific surface area and the large pore volume of
      103-180 m2/g and 0.40-0.86 cm3/g, respectively. Photocatalytic activity of the
      TiO2 hollow capsules was also investigated and compared to that of the commercial
      TiO2 nanoparticles.

PMID- 22630011
TI  - Influence of sintering temperature on photoluminescence of Gd2O3:Eu3+ phosphors
      prepared by liquid phase reaction method.
AB  - Nanostructured materials with diameters less than 100 nm have been studied
      vigorously in recent years. Many studies have been devoted on exceptional optical
      properties induced by quantum confinement for fundamental research and
      applications. For excellent luminescence characteristics, phosphor particles have
      to acquire fine size, narrow size distribution, non-aggregation, good
      crystalline, and spherical morphology. A liquid-phase reaction method was chosen
      in this study due to the low reaction temperature. Gd2O3:Eu3+ phosphors were
      synthesized by the liquid-phase reaction method and the effect of activation
      temperature on optical properties of the phosphors was investigated.

PMID- 22630012
TI  - Synthesis and characterization of bicalutamide-loaded magnetic nanoparticles as
      anti-tumor drug carriers.
AB  - This study examined the optical characteristics of bicalutamide-loaded
      magnetic/ethylene glycol composite nanoparticles (BMP), as well as their anti
      cancer activity against cancer cells. The gamma-Fe2O3 magnetic nanoparticles
      (MNPs), approximately 20 nm in diameter, were prepared via a chemical co
      precipitation method and coated with two surfactants to yield a water-based
      product. The characteristics of the particles were determined via X-ray
      diffraction (XRD), field emission scanning electron microscopy, and Raman
      spectrophotometry. The Raman spectra of the BMP showed peaks at 222, 283, 395,
      520, 669 and 1316 cm(-1), with broadened band in comparison to the Raman spectra
      of the magnetic nanoparticles. The BMP absorbance evidenced a rapid increase,
      with a broad peak at 409 nm, thus reflecting a good loading of the bicalutamide
      onto the magnetic nanoparticles. The results of the 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay showed that the MNPs were non-toxic against
      human brain cancer cells (SH-SY5Y), human cervical cancer cells (Hela), human
      liver cancer cells (HepG2), breast cancer cells (MCF-7), colon cancer cells
      (CaCO2) and human prostate cancers (Du 145, PC3) tested herein. In particular,
      BMPs were cytotoxic at 56% against DU145 cells, at 74.37% in SH-SY5Y cells, and
      at 58% in Hela cells. Our results demonstrated the biological applicability of
      BMP nanoparticles as anticancer agents and as agents for enhanced drug delivery
      against human prostate cancer cells. Our results indicated that the MNPs were
      biostable and that the BMP functioned effectively as drug delivery vehicles.

PMID- 22630013
TI  - Synthesis of tin oxide nanoparticle film by cathodic electrodeposition.
AB  - Three-dimensional SnO2 nanoparticle films were deposited onto a copper substrate
      by cathodic electrodeposition in a nitric acid solution. A new formation
      mechanism for SnO2 films is proposed based on the oxidation of Sn2+ ion to Sn4+
      ion by NO+ ion and the hydrolysis of Sn4+. The particle size of SnO2 was
      controlled by deposition potential. The SnO2 showed excellent charge capacity
      (729 mAh/g) at a 0.2 C rate and high rate capability (460 mAh/g) at a 5 C rate.

PMID- 22630014
TI  - Study of surface morphology control and investigation of hexagonal indium nitride
      nanorods grown on GaN/sapphire substrate.
AB  - Heteroepitaxial growth of metal-catalyst-free indium nitride (InN) nanorods on
      GaN/sapphire substrates by radio-frequency metal-organic molecular beam epitaxy
      (RF-MOMBE) system was investigated. We found that different N/In flow ratios
      together with the growth temperatures greatly influenced the surface morphology
      of InN nanorods and their structural properties. The InN nanorods have been
      characterized in detail using X-ray diffraction (XRD), field emission scanning
      electron microscopy (FE-SEM). Optical property was evaluated by photoluminescence
      (PL) measurements. At lower growth temperatures, InN nanorods were successfully
      grown. A pronounced two-dimensional growth mode was observed at higher growth
      temperature of 500 degrees C, and these films showed preferred orientation along
      the c-axis. XRD patterns and SEM images reveal that InN nanorods has high quality
      wurtzite structure with FWHM approaching 900 arcsec, and they have uniform
      diameters of about 150 nm and length of about 800 nm. Meanwhile, no metallic
      droplet was observed at the end of the nanostructured InN, and this is strong
      evidence that the nanorods are grown via the self-catalyst process. The PL peak
      at 0.8 eV is attributed to the quantum confinement and Moss-Burstein effects.
      These observations provide some valuable insights into the physical-chemical
      process for manufacturing InN nanorods devices.

PMID- 22630015
TI  - Ultrasonically carbon coated Si nanoparticles for lithium ion batteries.
AB  - A new and simple method for making nano-sized silicon/carbon composite materials
      was developed. The composite powders were prepared by dispersing HF-etched SiNPs
      in CHCl3, followed by bath sonication. Transmission Electron Microscopy (TEM) was
      used to identify the carbon layer outside the silicon particle. Impedance
      spectroscopy and cyclic voltammetry confirmed the improved electrode conductivity
      due to the carbon layer and the subsequent increased involvement of the silicon
      in the lithiation/delithiation process. The optimal composition of the composite,
      20 wt.% SiNP/C, and 20 wt.% graphite, exhibited excellent cyclability after ten
      cycles with a reversible discharging capacity near 465 mAhg(-1) which is 1.5
      times larger than that of the graphite and SiNPs electrode without ultrasonic
      process.

PMID- 22630016
TI  - Effects of annealing conditions on microstructures of thin film using crystalline
      silicon nanoparticles for printable electronics.
AB  - Silicon thin film was formed by dropping silicon ink on a single-crystalline
      silicon substrate and further annealing. The effects of the annealing conditions
      on the microstructures of thin film were investigated in order to obtain a
      crystalline silicon thin film for application in the field of printable
      electronics. Silicon ink was prepared by dispersing silicon nanoparticles
      synthesized using inductive coupled plasma in a solvent, namely, propylene
      glycol. The silicon nanoparticles in the as-synthesized film were observed to
      melt at a temperature of less than 1000 degrees C, and a highly crystalline
      silicon thin film was obtained by annealing at 800 degrees C for 180 min.

PMID- 22630017
TI  - Variety of nanopatterns on different substrates using PS-b-PMMA and their
      applications.
AB  - High density arrays of nanostructures over a large area can be formed on a range
      of substrates, such as glass, GaN, SiO2 deposited silicon wafer, etc. by the self
      assembly of PS-b-PMMA block copolymers. The morphology of the polymer surface is
      strongly dependent on the thickness of the polymer layer. It is necessary to
      control the size and shape in order to get the desired properties. The deposition
      of a gold thin film on polymer-patterned glass followed by the removal of the
      remaining part of the polymer results in patterned gold on glass, which can be
      used as a transparent conducting electrode, where the conductivity and
      transparency depends on the thickness of gold and as well as on the connectivity
      of the gold pattern. Similarly, the polymer pattern can be transferred to an
      underlying GaN layer in an as grown LED, which increases the photoluminescence
      intensity making it useful as a photonic crystal.

PMID- 22630018
TI  - Silver nanoparticles are assembled only on the two facets of the rod template.
AB  - Although the focus of nano-research appears to be shifting to the creation of the
      secondary structures using primary nanoparticle (NP) building blocks, very
      complex preparation routes to assemble NPs have been reported so far. In this
      work, for the first time, we demonstrate that silver NPs can be organized to
      assemble on the two facets of the 1-dimensional rod template via facile one-step
      process. This method could potentially be used to prepare assembly of diverse
      metal, semiconductor, or metal oxide NPs in the one dimensional material form.

PMID- 22630019
TI  - The sub-micron hole array in sapphire produced by inductively-coupled plasma
      reactive ion etching.
AB  - The sub-micron hole array in a sapphire substrate was fabricated by using
      nanosphere lithography (NSL) combined with inductively-coupled-plasma reactive
      ion etching (ICP-RIE) technique. Polystyrene nanospheres of about 600 nm diameter
      were self-assembled on c-plane sapphire substrates by the spin-coating method.
      The diameter of polystyrene nanosphere was modified by using oxygen plasma in ICP
      RIE system. The size of nanosphere modified by oxygen plasma was varied from 550
      to 450 nm with different etching times from 15 to 35 s. The chromium thin film of
      100 nm thick was then deposited on the shrunk nanospheres on the substrate by
      electron-beam evaporation system. The honeycomb type chromium mask can be
      obtained on the sapphire substrate after the polystyrene nanospheres were
      removed. The substrate was further etched in two sets of chlorine/Argon and boron
      trichloride/Argon mixture gases at constant pressure of 50 mTorr in ICP-RIE
      processes. The 400 nm hole array in diameter can be successfully produced under
      suitable boron trichloride/Argon gas flow ratio.

PMID- 22630020
TI  - Catalyst-free metal-organic chemical vapor deposition growth of InN nanorods.
AB  - We demonstrated the successful growth of catalyst-free InN nanorods on (0001)
      Al2O3 substrates using metal-organic chemical vapor deposition. Morphological
      evolution was significantly affected by growth temperature. At 710 degrees C,
      complete InN nanorods with typical diameters of 150 nm and length of
      approximately 3.5 microm were grown with hexagonal facets. theta-2theta X-ray
      diffraction measurement shows that (0002) InN nanorods grown on (0001) Al2O3
      substrates were vertically aligned along c-axis. In addition, high resolution
      transmission electron microscopy indicates the spacing of the (0001) lattice
      planes is 0.28 nm, which is very close to that of bulk InN. The electron
      diffraction patterns also revealed that the InN nanorods are single crystalline
      with a growth direction along (0001) with (10-10) facets.

PMID- 22630021
TI  - Carrier transport mechanisms of phosphorescent organic light-emitting devices
      fabricated utilizing a N,N'-dicarbazolyl-3,5-benzene: 1,3,5-tri(phenyl-2
      benzimidazole)-benzene mixed host emitting layer.
AB  - The electrical and the optical properties of phosphorescent organic light
      emitting devices (PHOLEDs) fabricated utilizing a mixed host emitting layer (EML)
      consisting of N,N'-dicarbazolyl-3,5-benzene (mCP) and 1,3,5-tri(phenyl-2
      benzimidazole)-benzene (TPBi) were investigated to clarify the carrier transport
      mechanisms of PHOLEDs. While the operating voltage of the PHOLEDs with a mixed
      host EML significantly decreased due to the insertion of TPBi with a high
      electron mobility, the quantum efficiency of the PHOLEDs decreased due to the
      hindrance of the exciton energy transfer by TPBi molecules. The
      electroluminescence spectra for the PHOLEDs with an tris(2-phenylpyridine)iridium
      doped mixed host EML showed that the TPBi molecules in the mixed host EML
      increased the electron injection into the mixed host EML, resulting in a decrease
      of the shift length of the recombination zone in comparison with a single host
      EML.

PMID- 22630022
TI  - Effects of the mixing ratio of the CaAl12O19:mn and Zn2SiO4:mn color-conversion
      layer on the color tunable emissions of white organic light-emitting devices.
AB  - The optical properties of white organic light-emitting devices (WOLEDs)
      fabricated utilizing a CaAl12O19:Mn and Zn2SiO4:Mn phosphor layer were
      investigated. X-ray diffraction patterns for CaAl12O19:Mn and Zn2SiO4:Mn
      phosphors showed that Mn ions in the CaAl12O19:Mn phosphors were completely
      substituted into Ca ions and that Mn ions in the Zn2SiO4:Mn phosphors were
      completely substituted into Zn ions. Field emission scanning electron microscopy
      images showed that the size of the CaAl12O19:Mn phosphor was approximately
      between 0.1 and 3 microm, and that the size of the Zn2SiO4:Mn phosphor was
      smaller than 7 microm. The color coordinates of the electroluminescence spectra
      for WOLEDs with phosphor thicknesses of 0.25 and 0.35 mm shifted to the white
      emission side because the generated blue light from the blue OLEDs combined with
      the red and green lights was converted by the CaAl12O19:Mn and the Zn2SiO4:Mn
      phosphor down-conversion layers.

PMID- 22630023
TI  - Structural characteristics of phosphorus-doped C60 thin film prepared by radio
      frequency-plasma assisted thermal evaporation technique.
AB  - Phosphorus doped C60 (P:C60) thin films were prepared by a radio frequency plasma
      assisted thermal evaporation technique using C60 powder as a carbon source and a
      mixture of argon and phosphine (PH3) gas as a dopant precursor. The effects of
      the plasma power on the structural characteristics of the as-prepared films were
      then studied using Raman spectroscopy, Auger electron spectroscopy (AES) and X
      ray photo-electrons spectroscopy (XPS). XPS and Auger analysis indicated that the
      films were mainly composed of C and P and that the concentration of P was
      proportional to the plasma power. The Raman results implied that the doped films
      contained a more disordered carbon structure than the un-doped samples. The P:C60
      films were then used as a coating layer for the Si anodes of lithium ion
      secondary batteries. The cyclic voltammetry (CV) analysis of the P:C60 coated Si
      electrodes demonstrated that the P:C60 coating layer might be used to improve the
      transport of Li-ions at the electrode/electrolyte interface.

PMID- 22630024
TI  - Effect of concentration on the photoluminescence properties of Sm3+ and Dy3+:
      cadmium lithium boro tellurite glasses.
AB  - Rare-earth (Sm3+ or Dy3+) ions doped cadmium lithium boro tellurite glasses have
      been prepared by melt quenching method for their spectral studies. From X-ray
      diffraction (XRD) patterns the glass amorphous nature has been confirmed. Vis-NIR
      absorption, excitation and emission spectra of these glasses have been analyzed
      systematically and also rare earth ion concentration is optimised Sm3+: CLiBT
      glasses have shown strong orange-reddish emission at 598 nm (4G5/2-->6H7/2) with
      an excitation wavelength lambda(exci) = 401 nm and Dy3+: CLiBT glasses have shown
      strong yellow emission at 574 nm (6F9/2-->6H13/2) with lambda(exci) = 451 nm.

PMID- 22630025
TI  - Structure analysis and magnetic properties of nano-sized Nb(x)Ni(y)Zn1-x-yFe2O4
      powders formed by combustion synthesis and mechanical milling.
AB  - Nano-sized Nb(x)Ni(y)Zn1-x-yFe2O4 ferrites with average particle size of less
      than 100 nm were prepared by using self-propagating high-temperature synthesis
      and mechanical ball milling. Average ferrites size of the SHS products were less
      than about 100 nm after 20 minutes mechanical milling. The average combustion
      temperatures and the combustion propagating rates were in the ranges of 1145 to
      1543 K and 4.1 to 7.2 mm/s, respectively. Rietveld refinement of the pattern
      converged to good agreement (chi2 = 4.87). Final product of SHS was
      Nb0.13Ni0.41Zn0.46Fe2O4 with Fd3m structure and the lattice parameter of 0.83623
      nm. Maximum magnetization (Ms), residual magnetization (Mr), coercive force (iHc)
      and susceptibility of the Nb0.013Ni0.41Zn0.46Fe2O4 ferrites formed at the oxygen
      pressure of 0.25 MPa were 12.30 Wb/m2 Kg, 1.57 Wb/m2 Kg, 6321 A/m, and 0.02
      m3/Kg, respectively. Niobium addition to nickel-zinc ferrites resulted in
      increasing Ms, Mr and iMc about 59%, 78% and 387%, respectively. Neutron
      diffractometry revealed that the variation of magnetic properties was related to
      non-stoichiometric number and oxygen position of the niobium-nickel-zinc ferrites
      due to the competitive reduction reaction among niobium, nickel and zinc oxides.

PMID- 22630026
TI  - Positron annihilation characterization of Fe-Y2O3 composite powder after
      mechanical alloying and heat treatment.
AB  - Fe-1 wt% Y2O3 composite powders were mechanically alloyed for 12 hr and then heat
      treated at 1050 degrees C for 1 hr. Positron annihilation lifetime and
      coincidence Doppler broadening measurements are in qualitative agreement with X
      ray diffraction studies, indicating that in the as-mixed Fe-1Y2O3 composite, up
      to approximately equal to 70% of the annihilations occur at vacancy clusters; a
      small fraction annihilates in its matrix. In the case of mechanically alloyed
      composite, up to approximately equal to 60% of the positrons annihilate at
      vacancy clusters. Some annihilations also occur in dislocations. In the heat
      treated Fe-1Y2O3, positrons primarily annihilate at yttria precipitates, while a
      small fraction annihilates in the matrix.

PMID- 22630027
TI  - Inkjet-printing of antimony-doped tin oxide (ATO) films for transparent
      conducting electrodes.
AB  - Antimony-doped Tin oxide (ATO) films have been prepared by inkjet-printing method
      using ATO nanoparticle inks. The electrical and optical properties of the ATO
      films were investigated in order to understand the effects of rapid thermal
      annealing (RTA) temperatures. The decrease in the sheet resistance and
      resistivity of the inkjet-printed ATO films was observed as the annealing
      temperature increased. The film annealed at 700 degrees C showed the sheet
      resistance of 1.7 x 10(3) Omega/sq with the film thickness of 350 nm. The optical
      transmittance of the films remained constant regardless of their annealing
      temperatures. In order to further reduce the sheet resistance of the films as
      well as the annealing temperature, Ag-grid was printed in between two layers of
      inkjet-printed ATO. With 1.5 mm Ag line spacing, the Ag-grid embedded ATO film
      showed the sheet resistance of 25.6 Omega/sq after RTA at 300 degrees C.

PMID- 22630028
TI  - Surface treatment effect of carbon fiber fabric counter electrode in dye
      sensitized solar cell.
AB  - Dye sensitized solar cells (DSSC) with surface modified carbon fiber fabric (CF)
      counter electrodes were prepared and tested. Four different type of CF were used;
      carbon fiber (CF); carbon fiber etched with NaOH (ECF); carbon fiber with
      thermally deposited platinum (CFPt); and carbon fiber etched with NaOH followed
      by thermal deposition of platinum (ECFPt). For comparison, DSSC with thermally Pt
      deposited fluorine doped tin oxide (FTO/Pt) glass counter electrode was also
      prepared and tested. Scanning electron microscope (SEM) proved that surface
      morphology of the carbon fiber was roughened by the etching process and platinum
      deposition process. The I-V curves of each DSSC were measured under simulated
      light (1 Sun, AM 1.5) to get open circuit voltage (Voc), short circuit current
      density (Jsc), fill factor (FF) and efficiency (eta). Electrochemical impedance
      spectroscopy of each cell was measured also. It was found that higher efficiency
      is obtained in order of using ECFPt > CFPt > FTO/Pt > ECF > CF counter electrode.

PMID- 22630029
TI  - Hydrothermal synthesized bismuth ferrites particles: thermodynamic, structural,
      and magnetic properties.
AB  - A family of bismuth ferrites (BFO), including Bi2Fe4O9, BiFeO3, and Bi25FeO39
      with different morphologies, has been prepared by the hydrothermal method
      assisted by different alkaline mineralizers. X-ray diffraction refinement
      calculations are carried out to study the crystal structures of bismuth ferrites.
      A thermodynamic calculation based on the dissolution-precipitation model was
      carried out to analyze the hydrothermal synthesis of BFO powders. Magnetic
      measurements of the obtained bismuth ferrites show different magnetic properties
      from 5 K to 350 K.

PMID- 22630030
TI  - Nano-scale precipitates formed in Cu-Co based alloys and their magnetic
      properties.
AB  - The microstructural evolutions of nano-scale magnetic Co particles formed in Cu
      Co base alloys have been investigated on isothermal annealing at 973 K, using
      transmission electron microscopy (TEM). After the solution treatment and short
      annealing, nano-scale magnetic particles appeared randomly in the Cu-rich matrix.
      With increasing the isothermal annealing time, however, pairs and sometimes more
      than two of Co precipitates were linearly arranged along <100> directions in Cu
      Co alloys. On the other hand, such linear arrangements of precipitates were
      extended in Cu-Ni-Co alloys. Co precipitates were cubic in the coherent stage and
      octahedral in incoherent stage of precipitation in binary alloys, while the
      precipitates rendered rectangular shapes even in the incoherent stage in Cu-Ni
      Co. The magnetic properties of the specimens have also been measured at the
      similar conditions, with the superconducting quantum interference device (SQUID)
      magnetometer. The present study revealed that coersive forces of the specimens
      were correlated with the microstructural evolution occurring during the
      isothermal annealing.

PMID- 22630031
TI  - Synthesis of organic-inorganic hybrid sols using trifunctional
      organoalkoxysilanes for dispersion agents.
AB  - We investigated the properties of synthetically produced organic-inorganic hybrid
      coatings by a sol-gel process. The properties of organic-inorganic hybrid
      materials arise from the synergism between the properties of the individual
      components. One of the typical way to synthesize the organic-inorganic hybrid
      materials is to use silica and silanes. A colloidal silica sol was used as an
      inorganic material. Methyltrimethoxysilane and phenyltrimethoxysilane were used
      as the trifunctional organoalkoxysilanes. Hybrid sols of colloidal silica and
      silanes were synthesized as a function of reaction time and
      methyltrimethoxysilane/phenyltrimethoxysilane ratio by a sol-gel process.
      Physical properties of sol solutions such as stability, viscosity, and
      transmittance were investigated. The surface roughness and surface free energy of
      the coatings were also measured.

PMID- 22630032
TI  - Influence of annealing on magnetic, relaxation and structural properties of
      composite and multilayer films.
AB  - This work is devoted to the research of influence of annealing to ferromagnetic
      resonance (FMR) properties of films of the A, B series with the compositions of
      (Co45-Fe45-Zr10)x(Al2O3)y, multilayer films of the D series with compositions
      {[(Co45-Fe45-Zr10)x(Al2O3)y]-[alpha-Si]}120 and revealing their relationship with
      the nanostructure characteristics. The films were obtained in an argon atmosphere
      (the A, D series) and with addition of oxygen (the B series). All samples were
      deposited on substrates by the ion-beam sputtering method and were annealed. The
      resonant fields and width of ferromagnetic resonance (FMR) line were measured
      before and after annealing. The changes in the FMR field and width of the line at
      varying temperatures of annealing for the composite and multilayer films are
      analyzed in the work. The character of changes in the structural characteristics
      of films at different annealing temperatures is determined.

PMID- 22630033
TI  - Characterization of the MgO nano powder synthesized by using a liquid phase
      precursor method for plasma display panels protecting layer.
AB  - The characterization of MgO nano powders that were synthesized using a
      conventional firing liquid phase precursor, rapid firing liquid phase precursor
      and rapid cooling firing liquid phase precursor were investigated as a function
      of the heating and cooling rates and the concentration of the impregnated
      Mg(NO3)2 x 6H2O solution from 1 to 20%. The relative intensity of diffraction
      peak in the MgO nano powder increased with increasing firing temperature from 800
      to 1200 degrees C, indicating a higher crystalline MgO nano powder. In addition,
      the relative intensities of the MgO nano powder synthesized at the designated
      temperature showed similar behavior regardless of the impregnated Mg(NO3)2 x 6H2O
      solution concentration from the XRD analysis. The field emission scanning
      electron microscope and high resolution transmission electron microscope analysis
      showed that the size and shape of the MgO nano powder can be controlled by the
      temperature, the firing and cooling processes, and the impregnated Mg(NO3)2 x
      6H2O solution concentration. Moreover, the CL spectra of the synthesized MgO nano
      powders showed a higher luminance efficiency than commercial MgO nano powder.

PMID- 22630034
TI  - Precursor solvent influence on preparation and electrochemical properties of
      platinum nanoparticles electrodes.
AB  - The crystalline sizes and loading efficiencies of metallic nanoparticles for fuel
      cell catalysts have been measured by changing solvent species containing
      precursors. By changing the solvent species containing carbon particles and metal
      salt, the microstructure and the according electrochemical property of catalysts
      could be controlled. Four kinds of solvent were investigated in this study. Pt
      catalysts that were deposited on carbon blacks supports by using an ethylene
      glycol solution showed the highest deposition efficiency, 85% and smallest
      crystalline size, 2.85 nm of particles. From the experimental result, it was
      concluded that the electrochemical performance of catalysts was dependent on the
      crystalline size and deposition efficiency of metal particles, by changing
      solvent species.

PMID- 22630035
TI  - Self-assembly of colloidal gamma-Fe2O3 and FePt nanoparticles on carbon nanotubes
      by dip-coating process.
AB  - The chemically synthesized colloidal gamma-Fe2O3 and FePt nanoparticles (NPs),
      with the diameter of approximately 10 nm and approximately 4 nm, respectively,
      adsorbed and assembled on the surface of carbon nanotubes (CNTs) by dip-coating
      process, through van der Waals interaction between NP and CNT. Repeating the
      steps of dip-coating and removing the surfactants from NPs significantly
      increased the amount of NPs as forming multilayers on the CNT. In addition, the
      electrochemical activities of FePt/CNTs for methanol oxidation were investigated
      for the potential application as catalysts of direct methanol fuel cells.

PMID- 22630036
TI  - Optical properties of electrochemically deposited ZnO thin films on colloidal
      crystal film of SiO2 microspheres.
AB  - The optical properties of electrochemically deposited ZnO thin films on colloidal
      crystal film of SiO2 microspheres structures were studied. Colloidal crystal film
      of SiO2 microspheres were self-assembled by evaporation using SiO2 in solution at
      a constant 0.1 wt%. ZnO in thin films was then electrochemically deposited on to
      colloidal crystal film of SiO2 microspheres. During electrochemical deposition,
      the content of Zn(NO3)2 x 6H2O in solution was 5 wt%, and the process's
      conditions were varied between of 2-4 V and 30-120 s at room temperature, with
      subsequent heat-treatment between 200 and 400 degrees C. A smooth surface and
      uniform thickness of 1.8 microm were obtained at 3 V for 90 s. The highest PL
      peak intensity was obtained in the ZnO thin film heat-treated at 400 degrees C.
      The double layered ZnO/SiO2 colloidal crystals showed clearly better emission
      properties than the SiO2/ZnO and ZnO structures.

PMID- 22630037
TI  - Gas-borne particles with tunable and highly controlled characteristics for
      nanotoxicology studies.
AB  - For nanotoxicology investigations of air-borne particles to provide relevant
      results it is ever so important that the particle exposure of, for example cells,
      closely resembles the "real" exposure situation, that the dosimetry is well
      defined, and that the characteristics of the deposited nanoparticles are known in
      detail. By synthesizing the particles in the gas-phase and directly depositing
      them on lung cells the particle deposition conditions in the lung is closely
      mimicked. In this work we present a setup for generation of gas-borne
      nanoparticles of a variety of different materials with highly controlled and
      tunable particle characteristics, and demonstrate the method by generation of
      gold particles. Particle size, number concentration and mass of individual
      particles of the population are measured on-line by means of differential
      mobility analyzers (DMA) and an aerosol particle mass analyzer (APM), whereas
      primary particle size and internal structure are investigated by transmission
      electron microscopy. A method for estimating the surface area dose from the DMA
      APM measurements is applied and we further demonstrate that for the setup used, a
      deposition time of around 1 h is needed for deposition onto cells in an air
      liquid interface chamber, using electrostatic deposition, to reach a
      toxicological relevant surface area dose.

PMID- 22630038
TI  - Three-dimensional coherent titania-mesoporous carbon nanocomposite and its
      lithium-ion storage properties.
AB  - Mesoporous, micro/nanosized TiO2/C composites with uniformly dispersed TiO2
      nanoparticles embedded in a carbon matrix have been rationally designed and
      synthesized. In brief, TiO2 precursor was infiltrated into the channels of
      surface-oxidized mesoporous carbon (CMK-3) by means of electrostatic interaction,
      followed by in situ hydrolysis and growth of TiO2 nanocrystallites, resulting in
      ultrafine TiO2 nanoparticle confined inside the channels of mesopores carbon.
      After chemical lithiation and post-annealing, TiO2 nanoparticles were transformed
      in situ into Li4Ti5O12 to form highly conductivity mesoporous Li4Ti5O12/C
      composite, as confirmed by scanning electron microscope (SEM), transmission
      electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, and
      nitrogen sorption isotherms. By combining high electronic conductivity, open
      mesoporosity, and nanosized active material, coherent mesoporous TiO2/C and
      Li4Ti5O12/C nanocomposites demonstrated high rate capability and good cycling
      properties. 

PMID- 22630039
TI  - Apoptotic cell death induced by 5-aminolaevulinic acid-mediated photodynamic
      therapy of hypertrophic scar-derived fibroblasts.
AB  - OBJECTIVE: To investigate the effects of 5-aminolevulinic acid (ALA)-mediated
      photodynamic therapy (PDT) on dermal fibroblasts from hypertrophic scars (HSs).
      METHODS: HS samples were obtained from five patients who underwent surgery, and
      normal skin from healthy donors was used as a control. Dermal fibroblasts were
      isolated and cultured with various concentrations of ALA for 6 h. Intracellular
      protoporphyrin IX (PpIX) was measured by confocal microscopy. After 5 h of ALA
      treatment, cells were irradiated by a red laser (635 nm wavelength) at a power
      density of 10 mW/cm(2) with an energy density from 0.5 to 4 J/cm(2). Cell
      survival was measured by a CCK-8 Kit after 24 h. Cell death was detected by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and flow
      cytometric analysis of annexin V. RESULTS: Intracellular PpIX accumulation was
      observed in fibroblasts from HS patients and healthy donors after ALA treatment.
      After laser irradiation, viable cells were decreased among both cell types in a
      dose-dependent manner with energy density. In addition, apoptotic cell death was
      observed with low dose PDT, whereas necrotic cells were increased by high dose
      PDT. CONCLUSION: HS-derived fibroblasts efficiently accumulate PpIX after ALA
      treatment and can be eliminated via apoptosis by controlled laser irradiation.

PMID- 22630040
TI  - Selenate-enriched urea granules are a highly effective fertilizer for selenium
      biofortification of paddy rice grain.
AB  - This study examined the effects of applied selenium (Se) species, time of
      application, method of application, and soil water management regimen on the
      accumulation of Se in rice plants. Plants were grown to maturity in a temperature
      and humidity-controlled growth chamber using three water management methods:
      field capacity (FC), submerged until harvest, and submerged and drained 2 weeks
      before harvest. Two Se species, selenate (SeO4(2-)) and selenite (SeO3(2-)), were
      applied at a rate equivalent to 30 g ha(-1). Four application methods were
      employed as follows: (i) Se applied at soil preparation, (ii) Se-enriched urea
      granules applied to floodwater at heading; (iii) foliar Se applied at heading;
      and (iv) fluid fertilizer Se applied to soil or floodwater at heading. Total Se
      concentrations in rice grains, husks, leaves, culms, and roots were measured, as
      well as Se speciation in grains from the Se-enriched urea granule treatment.
      Highest Se concentrations in the grain occurred with SeO4(2-) and with fertilizer
      applied at heading stage; SeO4(2-)-enriched urea granules applied at heading
      increased grain Se concentrations 5-6-fold (by 450-600 MUg kg(-1)) compared to
      the control (no fertilizer Se applied) in all water treatments. Under paddy
      conditions other Se fertilization strategies were much less effective. Drainage
      before harvesting caused Se to accumulate in/on rice roots, possibly through
      adsorption onto iron plaque on roots. Rice grains contained Se mainly in the
      organic form as selenomethionine (SeM), which comprised >90% of the total grain
      Se in treatments fertilized with SeO4(2-)-enriched urea granules. The results of
      this study clearly show that of the fertilizer strategies tested biofortification
      of Se in rice grains can best be achieved in lowland rice by broadcast
      application of SeO4(2-)-enriched urea granules to floodwater at heading stage. 

PMID- 22630041
TI  - U.S. and European severe asthma cohorts: what can they teach us about severe
      asthma?
AB  - Asthma is a global health problem affecting around 300 million patients of all
      ages and ethnic groups in all countries around the world. In the majority of
      subjects with persistent, mild-to-moderate asthma (MA), the disease can be
      relatively well controlled by the use of currently available medications;
      however, five to ten per cent of patients suffer from a particularly severe
      disease that is poorly controlled clinically and often refractory to usual
      treatment. Improved care of severe asthma (SA) is a major unmet medical need and
      several international consortia aim at improving our understanding of mechanisms
      in SA. To manage SA better, standardized definitions and concepts of asthma
      severity, risk and level of control are critical. In the following sections, we
      present several guidelines approaches and definitions followed by an overview of
      U.S. (SARP) and European (ENFUMOSA, BIOAIR, U-BIOPRED) SA networks. Key findings
      regarding SA phenotypes, risk factors and pathophysiology are discussed.
      International cooperation in the area of respiratory diseases, including SA,
      across the Atlantic Ocean, will lead to a better understanding of asthma
      pathology, especially of those severe, not well controlled or difficult-to-treat
      cases.

PMID- 22630042
TI  - Deaf and hearing children's plural noun spelling.
AB  - The present study examines deaf and hearing children's spelling of plural nouns.
      Severe literacy impairments are well documented in the deaf, which are believed
      to be a consequence of phonological awareness limitations. Fifty deaf (mean
      chronological age 13;10 years, mean reading age 7;5 years) and 50 reading-age
      matched hearing children produced spellings of regular, semiregular, and
      irregular plural nouns in Experiment 1 and nonword plurals in Experiment 2. Deaf
      children performed reading-age appropriately on rule-based (regular and
      semiregular) plurals but were significantly less accurate at spelling irregular
      plurals. Spelling of plural nonwords and spelling error analyses revealed clear
      evidence for use of morphology. Deaf children used morphological generalization
      to a greater degree than their reading-age-matched hearing counterparts. Also,
      hearing children combined use of phonology and morphology to guide spelling,
      whereas deaf children appeared to use morphology without phonological mediation.
      Therefore, use of morphology in spelling can be independent of phonology and is
      available to the deaf despite limited experience with spoken language. Indeed,
      deaf children appear to be learning about morphology from the orthography.
      Education on more complex morphological generalization and exceptions may be
      highly beneficial not only for the deaf but also for other populations with
      phonological awareness limitations.

PMID- 22630044
TI  - A multi-tiered intervention to address behavioural and cognitive changes after
      diagnosis of primary brain tumour: a feasibility study.
AB  - PURPOSE: Untreated behavioural and cognitive changes after primary brain tumour
      (PBT) can result in challenging behaviours (CBs), with limited documentation on
      treatment approaches. This study explored the feasibility of employing a
      Behavioural Consultancy approach to manage CBs, targeting individuals with PBT,
      family and treating staff. METHODS: Participants were patients and families of
      two hospitals and health professionals from cancer/neurological services. A
      single-case experimental design piloted skill-based training and environmental
      changes in managing socio-behavioural impairments in a person with a low grade
      astrocytoma. A half-day workshop to train family members (n = 7) in compensatory
      strategy use to manage CBs after PBT was piloted. Finally, a 1-day workshop was
      provided to 43 health professionals in managing CBs after PBT. For both
      workshops, a pre-post impact evaluation was conducted employing a purpose
      designed Strategies Use Measure. RESULTS: All three interventions demonstrated
      positive results. The single case showed a 71% decrease in the target behaviour
      (time spent talking) post-intervention. Some attrition to these gains was
      observed at two follow-up time points (3 and 5 months). Participants from both
      workshops demonstrated significant post-intervention increases in perceived
      knowledge of Strategy Use (family members z = 2.03, p < 0.05; health
      professionals z = 4.95, p < 0.00; Wilcoxon signed-rank test). CONCLUSIONS: These
      initial studies highlight the potential of employing an integrated multi-tiered
      intervention based on a Behavioural Consultancy model to manage CBs after PBT.

PMID- 22630043
TI  - Prevalence and trends of the diabetes epidemic in South Asia: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Diabetes mellitus has reached epidemic proportions worldwide. South
      Asians are known to have an increased predisposition for diabetes which has
      become an important health concern in the region. We discuss the prevalence of
      pre-diabetes and diabetes in South Asia and explore the differential risk factors
      reported. METHODS: Prevalence data were obtained by searching the Medline(r)
      database with; 'prediabetes' and 'diabetes mellitus' (MeSH major topic) and
      'Epidemology/EP' (MeSH subheading). Search limits were articles in English,
      between 01/01/1980-31/12/2011, on human adults (>=19 years). The conjunction of
      the above results was narrowed down with country names. RESULTS: The most recent
      reported prevalence of pre-diabetes:diabetes in regional countries were;
      Bangladesh-4.7%:8.5% (2004-2005;Rural), India-4.6%:12.5% (2007;Rural); Maldives
      3.0%:3.7% (2004;National), Nepal-19.5%:9.5% (2007;Urban), Pakistan-3.0%:7.2%
      (2002;Rural), Sri Lanka-11.5%:10.3% (2005-2006;National). Urban populations
      demonstrated a higher prevalence of diabetes. An increasing trend in prevalence
      of diabetes was observed in urban/rural India and rural Sri Lanka. The diabetes
      epidemicity index decreased with the increasing prevalence of diabetes in
      respective countries. A high epidemicity index was seen in Sri Lanka (2005/2006
      52.8%), while for other countries, the epidemicity index was comparatively low
      (rural India 2007-26.9%; urban India 2002/2005-31.3%, and urban Bangladesh
      33.1%). Family history, urban residency, age, higher BMI, sedentary lifestyle,
      hypertension and waist-hip ratio were associated with an increased risks of
      diabetes. CONCLUSION: A significant epidemic of diabetes is present in the South
      Asian region with a rapid increase in prevalence over the last two decades. Hence
      there is a need for urgent preventive and curative strategies.

PMID- 22630045
TI  - Glycan structures and intrageneric variations of venom acidic phospholipases A(2)
      from Tropidolaemus pitvipers.
AB  - Most of the phospholipases A(2)  (PLA(2) ; EC3.1.1.4) variants isolated so far
      from snake venoms are nonglycosylated enzymes. In the present study, we purified
      an active glycosylated PLA(2)  and an inactive nonglycosylated Lys49-like PLA(2) 
      from two geographical venom samples of Tropidolaemus. The PLA(2)  variants from
      the two samples have rather different N-terminal sequences, implying that the
      samples were probably derived from two species (Tropidolaemus subannulatus and
      Tropidolaemus wagleri). The active PLA(2) s from Sulawesi and Sumatra venoms were
      designated as Tsu-E6 and Twa-E6, respectively, as a result of the presence of
      their conserved Glu6 residue. Tsu-E6 inhibited ADP-induced aggregation of mouse
      and human platelets. Twa-E6 stimulated the aggregation of mouse platelets but
      inhibited the aggregation of human platelets. Both PLA(2) s were found to be
      glycosylated at Asn14. Using MALDI-TOF analysis, the released glycans were shown
      to comprise complex type oligosaccharides without sialylation. This is the first
      glycan structure of the snake venom PLA(2)  to be solved. Furthermore, the
      enzymatic removal of glycans from both PLA(2) s did not significantly alter their
      effects on lipid hydrolysis and platelet aggregation. The thermostability of
      glycosylated Twa-E6 was also found to be as good as that of other homologous
      PLA(2) s. The presence of these oligosaccharides in PLA(2) s warrants further
      analyses, which may provide useful insights into the functional regulation of
      these biomolecules.

PMID- 22630046
TI  - Genomic diversity of the human intestinal parasite Entamoeba histolytica.
AB  - BACKGROUND: Entamoeba histolytica is a significant cause of disease worldwide.
      However, little is known about the genetic diversity of the parasite. We re
      sequenced the genomes of ten laboratory cultured lines of the eukaryotic pathogen
      Entamoeba histolytica in order to develop a picture of genetic diversity across
      the genome. RESULTS: The extreme nucleotide composition bias and repetitiveness
      of the E. histolytica genome provide a challenge for short-read mapping, yet we
      were able to define putative single nucleotide polymorphisms in a large portion
      of the genome. The results suggest a rather low level of single nucleotide
      diversity, although genes and gene families with putative roles in virulence are
      among the more polymorphic genes. We did observe large differences in coverage
      depth among genes, indicating differences in gene copy number between genomes. We
      found evidence indicating that recombination has occurred in the history of the
      sequenced genomes, suggesting that E. histolytica may reproduce sexually.
      CONCLUSIONS: E. histolytica displays a relatively low level of nucleotide
      diversity across its genome. However, large differences in gene family content
      and gene copy number are seen among the sequenced genomes. The pattern of
      polymorphism indicates that E. histolytica reproduces sexually, or has done so in
      the past, which has previously been suggested but not proven.

PMID- 22630047
TI  - A critique of the European Commission document, "State of the Art Assessment of
      Endocrine Disrupters".
AB  - In this commentary, we critique a recently finalized document titled "State of
      the Art Assessment of Endocrine Disrupters" (SOA Assessment). The SOA Assessment
      was commissioned by the European Union Directorate-General for the Environment to
      provide a basis for developing scientific criteria for identifying endocrine
      disruptors and reviewing and possibly revising the European Community Strategy on
      Endocrine Disrupters. In our view, the SOA Assessment takes an anecdotal approach
      rather than attempting a comprehensive assessment of the state of the art or
      synthesis of current knowledge. To do the latter, the document would have had to
      (i) distinguish between apparent associations of outcomes with exposure and the
      inference of an endocrine-disruption (ED) basis for those outcomes; (ii)
      constitute a complete and unbiased survey of new literature since 2002 (when the
      WHO/IPCS document, "Global Assessment of the State-of-the-Science of Endocrine
      Disruptors" was published); (iii) consider strengths and weaknesses and issues in
      interpretation of the cited literature; (iv) follow a weight-of-evidence
      methodology to evaluate evidence of ED; (v) document the evidence for its
      conclusions or the reasoning behind them; and (vi) present the evidence for or
      reasoning behind why conclusions that differ from those drawn in the 2002
      WHO/IPCS document need to be changed. In its present form, the SOA Assessment
      fails to provide a balanced and critical assessment or synthesis of literature
      relevant to ED. We urge further evidence-based evaluations to develop the needed
      scientific basis to support future policy decisions.

PMID- 22630048
TI  - Effect of melt sonocrystallization on pharmacotechnical properties of
      paracetamol, indomethacin and mefenamic acid characterized by dynamic laser
      scattering and its impact on solubility.
AB  - The purpose of the research was to employ a novel particle engineering technique
      melt sonocrystallization (MSC) for some nonsteroidal anti-inflammatory drugs for
      development of more soluble forms of the drugs without the use of excipients. The
      original forms of Paracetamol (OFPCM), Indomethacin (OFIMC) and Mefenamic acid
      (OFMA) were subjected to MSC to improve physicochemical properties. MSC forms of
      PCM, IMC and MA were subjected to dynamic laser scattering for particle size
      analysis to quantize mean particle size, specific surface area, interquartile
      coefficient of skewness, kurtosis and span. Rheological and solubility analysis,
      X-ray powder diffraction and scanning electron microscopy were conducted for
      validating the effect of MSC on powder particles. On melt sonocrystallized form
      of drug powders exhibited improved micromeritic properties, the mean particle
      size was reduced while the specific surface area increased effectively. Frequency
      distribution curves showed reduction in asymmetry and skewness that was confirmed
      by interquartile coefficient of skewness values. Equilibrium solubility of MSC
      form of PCM, IMC and MA was higher than the original forms. Similarly the
      intrinsic dissolution rate was approximately 1.5 times higher in comparison to
      original form of drugs. X-ray powder diffraction shows decreased relative
      intensities of peaks of MSC forms due to reduction in the crystallinity that was
      confirmed by visualization of MSC particles by scanning electron microscopy.
      Conclusively, MSC is a promising cost-effective technique that may afford powder
      with improved flow and formulative properties as well as improved solubility and
      dissolution.

PMID- 22630049
TI  - Addendum.

PMID- 22630051
TI  - The Journal of Biomolecular Structure and Dynamics Establishes Web Site: The JBSD
      WWW Edition.

PMID- 22630052
TI  - Cancer Watch Establishes Web Site: The CANCER WATCH WWW Edition.

PMID- 22630053
TI  - Immune regulatory gene polymorphisms as predisposing risk factors for the
      development of factor VIII inhibitors in Indian severe haemophilia A patients.
AB  - Development of inhibitors to factor VIII, a serious complication of replacement
      therapy in haemophilia A patients, leads to increased bleeding, morbidity and
      mortality. There is no data on the risk factors for inhibitor development in
      Indian patients with severe haemophilia A. Our aim was to study the role of
      immune regulatory gene polymorphisms in the development of inhibitors. Fourteen
      immune regulatory gene polymorphisms (IL1beta, IL4, IL10, TNFA and CTLA4) were
      analysed in 120 patients with severe haemophilia A, i.e. 50 inhibitor positive
      patients, and 70 inhibitor negative control patients, by PCR-RFLP, DNA sequencing
      and allele-specific PCRs. The IL10 promoter 'GCC' haplotypes overall (P: 0.002,
      OR: 3.452, 95% CI: 1.607-7.416), and 'GCC/ATA' (P: 0.011, OR: 3.492, 95% CI:
      1.402-8.696) haplotype, associated with high and intermediate IL10 production,
      respectively, were significantly higher in inhibitor positive patients, whereas
      the 'non-GCC' haplotypes overall (P: 0.002,OR: 0.290, 95% CI 0.135-0.622) and
      'ATA/ATA' haplotype (P: 0.025, OR: 0.278, 95% CI: 0.096-0.802), associated with
      low IL10 synthesis, were significantly higher among inhibitor negative patients.
      The TNFA rs1799724 C/T heterozygote prevalence was significantly higher in the
      inhibitor positive group (P: 0.021, OR: 3.190, 95% CI: 1.273-7.990), whereas the
      other polymorphisms showed no statistically significant association with the
      presence of inhibitors. Different immune regulatory gene polymorphisms play a
      significant role as possible risk factors for the development of inhibitors in
      severe haemophilia A patients.

PMID- 22630054
TI  - Eukaryotes in Arctic and Antarctic cyanobacterial mats.
AB  - Cyanobacterial mats are commonly found in freshwater ecosystems throughout the
      polar regions. Most mats are multilayered three-dimensional structures with the
      filamentous cyanobacteria embedded in a gel-like matrix. Although early
      descriptions mentioned the presence of larger organisms including metazoans
      living in the mats, there have been few studies specifically focused on the
      microbial eukaryotes, which are often small cells with few morphological features
      suitable for identification by microscopy. Here, we applied 18S rRNA gene clone
      library analysis to identify eukaryotes in cyanobacterial mat communities from
      both the Antarctic and the extreme High Arctic. We identified 39 ribotypes at the
      level of 99% sequence similarity. These consisted of taxa within algal and other
      protist groups including Chlorophyceae, Prasinophyceae, Ulvophyceae,
      Trebouxiophyceae, Bacillariophyceae, Chrysophyceae, Ciliophora, and Cercozoa.
      Fungi were also recovered, as were 21 metazoan ribotypes. The eukaryotic taxa
      appeared habitat-specific with little overlap between lake, pond, and ice shelf
      communities. Some ribotypes were common to both Arctic and Antarctic mats,
      suggesting global dispersal of these taxa and similarity in the environmental
      filters acting on protist communities. Many of these eukaryotic taxa likely
      benefit from protected, nutrient-rich microhabitats within the cyanobacterial mat
      environment.

PMID- 22630055
TI  - Diacetoxyiodobenzene mediated one-pot synthesis of diverse carboxamides from
      aldehydes.
AB  - A novel, one-pot, and highly facile protocol has been devised for an easy access
      of a series of novel glycosyl carboxamides from aldehydes using
      diacetoxyiodobenzene in the presence of ionic liquid at ambient temperature.

PMID- 22630056
TI  - Human papillomavirus type 56-associated Bowen disease.
AB  - BACKGROUND: Some cases of human papillomavirus (HPV) type 56 infection in Bowen
      disease have been reported. However, the incidence and clinical characteristics
      are still unclear. OBJECTIVE: To clarify the prevalence of HPV type 56-positive
      Bowen disease in our department and to characterize the clinical manifestations.
      METHODS: Sixty-eight specimens of Bowen disease were examined by polymerase chain
      reaction using HPV consensus primers, and the amplified products were subjected
      to DNA sequence analyses. Moreover, positive samples were investigated by in situ
      hybridization. These findings were used to clarify the clinical characteristics
      of HPV-positive Bowen disease. RESULTS: Eight out of 68 specimens (12%) of Bowen
      disease were HPV-positive, of which six specimens were HPV type 56-positive. The
      HPV type 56-positive lesions were characterized by a longitudinal melanonychia or
      a deeply pigmented keratotic lesion. The remaining two specimens were genital
      Bowen disease in which HPV type 16 was detected. In situ hybridization
      demonstrated the positive cells in the upper layer of epidermis. The HPV type 56
      detected in the samples of longitudinal melanonychia can be divided into at least
      into two types. CONCLUSIONS: This study determined the prevalence of HPV type 56
      positive Bowen disease. Longitudinal melanonychia is the most characteristic
      manifestation of HPV type 56-associated Bowen disease.

PMID- 22630057
TI  - Evaluating observer agreement of scoring systems for foot integrity and footrot
      lesions in sheep.
AB  - BACKGROUND: A scoring scale with five ordinal categories is used for visual
      diagnosis of footrot in sheep and to study its epidemiology and control. More
      recently a 4 point ordinal scale has been used by researchers to score foot
      integrity (wall and sole horn damage) in sheep. There is no information on
      observer agreement using either of these scales. Observer agreement for ordinal
      scores is usually estimated by single measure values such as weighted kappa or
      Kendall's coefficient of concordance which provide no information where the
      disagreement lies. Modeling techniques such as latent class models provide
      information on both observer bias and whether observers have different thresholds
      at which they change the score given. In this paper we use weighted kappa and
      located latent class modeling to explore observer agreement when scoring footrot
      lesions (using photographs and videos) and foot integrity (using post mortem
      specimens) in sheep. We used 3 observers and 80 photographs and videos and 80
      feet respectively. RESULTS: Both footrot and foot integrity scoring scales were
      more consistent within observers than between. The weighted kappa values between
      observers for both footrot and integrity scoring scales ranged from moderate to
      substantial. There was disagreement between observers with both observer bias and
      different thresholds between score values. The between observer thresholds were
      different for scores 1 and 2 for footrot (using photographs and videos) and for
      all scores for integrity (both walls and soles). The within observer agreement
      was higher with weighted kappa values ranging from substantial to almost perfect.
      Within observer thresholds were also more consistent than between observer
      thresholds. Scoring using photographs was less variable than scoring using video
      clips or feet. CONCLUSIONS: Latent class modeling is a useful method for
      exploring components of disagreement within and between observers and this
      information could be used when developing a scoring system to improve
      reliability.

PMID- 22630058
TI  - ABCC2 polymorphisms and haplotype are associated with drug resistance in Chinese
      epileptic patients.
AB  - AIMS: Some study found that ATP-binding cassette (ABC) efflux transporters play
      an important role in antiepileptic drug resistance, especially ABCB1 and ABCC2.
      The aims of this study were to evaluate the relationship between the genetic
      polymorphisms of ABCC2 and ABCB1 and the therapeutic efficacy of antiepileptic
      drugs (AEDs) in Chinese epileptic patients. METHODS: ABCB1 rs1045642 (3435C>T)
      and ABCC2 rs717620 (-24C>T), rs3740066 (3972C>T), and rs2273697 (1249G>A)
      polymorphisms loci in 537 Chinese epilepsy patients (217 drug resistant patients
      and 320 drug responders) were genotyped by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). RESULTS: ABCC2 rs717620 -24TT genotype
      was significantly associated with drug resistant epilepsy (odds ratio [OR]= 4.06
      [1.79-9.20], P= 0.001). The OR values of ABCC2 rs717620 -24 CT+TT genotypes and
      ABCC2 rs3740066 (3972C>T) CT+TT genotypes were markedly higher in drug resistant
      patients (OR = 1.57 [1.08-2.29], P= 0.018; OR = 1.49 [1.02-2.18], P= 0.038,
      respectively) compared with responsive patients. ABCC2 rs2273697 (1249G>A) and
      ABCB1 rs1045642 (3435C>T) polymorphisms were not associated with drug resistant
      epilepsy. Linkage disequilibrium (LD) test showed that the ABCC2 rs717620 were in
      strong LD with rs2273697 (D'= 0.694) and rs3740066 (D'= 0.699). The frequencies
      of haplotypes TGT (ABCC2 -24C>T/ABCC2 1249G>A/ABCC2 3972C>T) in resistant
      patients was significantly higher than those in responsive patients (21.0% vs.
      14.2%, P < 0.05). CONCLUSION: ABCC2-24C>T, 3972C>T polymorphisms and one ABCC2
      haplotype is associated with AED resistance; ABCC2 1249G>A and ABCB1 3435C>T
      polymorphisms are not associated with AED resistance in our study. These data
      suggest that ABCC2 polymorphisms and haplotype may affect the response of
      antiepileptic drugs.

PMID- 22630059
TI  - Endotracheal tubes and intubation.

PMID- 22630060
TI  - New minimally invasive technique for repairing femoral hernias: 3-D patch device
      through a femoris approach.
AB  - BACKGROUND: Femoral hernias are less common than inguinal hernias. The use of
      preformed mesh to repair femoral hernias without tension has become increasingly
      common. We sought to investigate the safety and feasibility of repairing femoral
      hernias with a Prolene 3-dimentional (3-D) patch using a femoris approach.
      METHODS: We identified all consecutive patients with femoral hernias treated at
      our centre with a Prolene 3-D patch using a femoris approach in our institution
      over a 5-year period (2004-2009). We assessed duration of surgery, length of stay
      in hospital, recurrence, postoperative pain and complications. RESULTS: We
      repaired 73 hernias with this technique during the study period. The mean
      duration of surgery was 13.1 minutes, most patients were discharged in less than
      24 hours, no recurrence was noted, and only minor complications occurred.
      CONCLUSION: This technique has not only the same advantage of other tension-free
      repairs, but also the advantages of convenience and shorter duration of surgery.

PMID- 22630061
TI  - Comparison of lifetime incremental cost:utility ratios of surgery relative to
      failed medical management for the treatment of hip, knee and spine osteoarthritis
      modelled using 2-year postsurgical values.
AB  - BACKGROUND: Demand for surgery to treat osteoarthritis (OA) of the hip, knee and
      spine has risen dramatically. Whereas total hip (THA) and total knee arthroplasty
      (TKA) have been widely accepted as cost-effective, spine surgeries
      (decompression, decompression with fusion) to treat degenerative conditions
      remain underfunded compared with other surgeries. METHODS: An incremental cost
      utility analysis comparing decompression and decompression with fusion to THA and
      TKA, from the perspective of the provincial health insurance system, was based on
      an observational matched-cohort study of prospectively collected outcomes and
      retrospectively collected costs. Patient outcomes were measured using short-form
      (SF)-36 surveys over a 2-year follow-up period. Utility was modelled over the
      lifetime, and quality-adjusted life years (QALYs) were determined. We calculated
      the incremental cost per QALY gained by estimating mean incremental lifetime
      costs and QALYs of surgery compared with medical management of each diagnosis
      group after discounting costs and QALYs at 3%. Sensitivity analyses were also
      conducted. RESULTS: The lifetime incremental cost:utility ratios (ICURs)
      discounted at 3% were $5321 per QALY for THA, $11,275 per QALY for TKA, $2307 per
      QALY for spinal decompression and $7153 per QALY for spinal decompression with
      fusion. The sensitivity analyses did not alter the ranking of the lifetime ICURs.
      CONCLUSION: In appropriately selected patients with leg-dominant symptoms
      secondary to focal lumbar spinal stenosis who have failed medical management, the
      lifetime ICUR for surgical treatment of.

PMID- 22630062
TI  - Hemithyroidectomy is the preferred initial operative approach for an
      indeterminate fine needle aspiration biopsy diagnosis.
AB  - BACKGROUND: Fine needle aspiration biopsy represents the critical initial
      diagnostic test used for evaluation of thyroid nodules. Our objectives were to
      determine the cytological distribution, the utility of clinicopathologic
      characteristics for predicting malignancy and the true proportion of cancer among
      individuals who presented with indeterminate cytology and had undergone thyroid
      surgery for suspicion of cancer. METHODS: We retrospectively reviewed 1040
      consecutive primary thyroid operations carried out over an 8-year period at a
      tertiary care endocrine referral centre. Follicular neoplasm (FN), Hurthle cell
      neoplasm (HN), neoplasms suspicious for but not diagnostic of papillary carcinoma
      (IP) and neoplasms with cellular atypia (IA) were reviewed. RESULTS: In all, 380
      individuals presented with cytologically indeterminate thyroid nodules. Of these,
      252 (66%) patients had FN, 47 (12%) HN, 44 (12%) IP, 26 (7%) IA and 11 (4%) had
      mixed diagnoses. Biopsied lesions were found to be malignant on pathological
      evaluation in 102 (27%) patients: 49 (19%) with FN, 11 (23%) HN, 28 (64%) IP and
      9 (35%) with IA. Hemithyroidectomy was adequate definitive treatment in 196 of
      225 (87%) patients with FN and 39 of 42 (93%) with HN. Significant associations
      with a cancer diagnosis were identified for smaller tumour size in patients with
      FN (p = 0.004) and right thyroid lobe location in patients with IP (p = 0.012),
      although these factors were nonsignificant in the corrected analyses for multiple
      comparisons. CONCLUSION: In a review of the experience at a Canadian centre, 4
      operations were carried out to identify each cancer, and hemithyroidectomy was
      the optimal initial and definitive surgical approach for most patients.

PMID- 22630063
TI  - CAGS and ACS Evidence Based Reviews in Surgery. 41. Cost-utility analysis of
      early versus delayed laparoscopic cholecystectomy for acute cholecystitis.

PMID- 22630064
TI  - Users' Guide to the Surgical Literature. Understanding confidence intervals.

PMID- 22630066
TI  - Conservative or operative management (open or laparoscopic) of acute
      appendicitis.

PMID- 22630068
TI  - What is a reportable error in surgery?

PMID- 22630069
TI  - [What is a reportable error in surgery?].

PMID- 22630070
TI  - A tribute to Nils G. Kock, 1924-2011.

PMID- 22630071
TI  - Humanitarian cardiac care in Arequipa, Peru: experiences of a multidisciplinary
      Canadian cardiovascular team.
AB  - BACKGROUND: The prevalence of cardiovascular disease and its associated mortality
      continue to increase in developing countries despite unparalleled improvements in
      cardiovascular medicine over the last century. Cardiovascular care in developing
      nations is often constrained by limited resources, poor access, lack of specialty
      training and inadequate financial support. Medical volunteerism by experienced
      health care teams can provide mentorship, medical expertise and health policy
      advice to local teams and improve cardiovascular patient outcomes. METHODS: We
      report our experience from annual successive humanitarian medical missions to
      Arequipa, Peru, and describe the challenges faced when performing cardiovascular
      interventions with limited resources. RESULTS: Over a 2-year period, we performed
      a total of 15 cardiac repairs in patients with rheumatic, congenital and ischemic
      heart disease. We assessed and managed 150 patients in an outpatient clinic,
      including 7 patients at 1-year postoperative follow-up. CONCLUSION: Despite
      multiple challenges, we were able to help the local team deliver advanced
      cardiovascular care to many patients with few alternatives and achieve good early
      and 1-year outcomes. Interdisciplinary education at all levels of cardiac care,
      including preoperative assessment, intraoperative surgical and anesthetic
      details, and postoperative critical care management, were major goals for our
      medical missions.

PMID- 22630073
TI  - Susceptibility of cord blood antioxidant enzymes glutathione reductase,
      glutathione peroxidase and glutathione S-transferase to different antibiotics: in
      vitro approach.
AB  - Cord blood has numerous facilities for life and used in many different areas.
      Cord blood contains many different catalytic proteins including antioxidant
      enzymes. Here we purified human cord blood glutathione reductase (hcbGR),
      glutathione S-transferase (hcbGST) and human cord blood glutathione peroxidase
      (hcbGPx) from human cord blood erythrocytes and analyzed the inhibition effects
      of the antibiotics incorporating cefuroxime, ceftriaxone, ceftizoxime and
      cefoperazone, on these enzymes. K(I) values for the drugs ranged from 10.42 to
      28.72 uM for hcbGR, 32.7 to 244.8 uM for hcbGPx, and 32.39 to 267.3 uM for
      hcbGST. Cefuroxime caused the highest inhibition on all enzymes with KI values of
      10.42, 32.39, 32.7 uM for hcbGR, hcbGST, and hcbGPx, respectively. All drugs
      displayed non-competitive inhibition regardless of their structures. Since these
      drugs are often used during pregnancy, identification of possible undesired
      impacts on various parameters has a great importance for pharmacological and
      medical applications.

PMID- 22630074
TI  - Minor iridoids from Scutellaria albida ssp. albida. Inhibitory potencies on
      lipoxygenase, linoleic acid lipid peroxidation and antioxidant activity of
      iridoids from Scutellaria sp.
AB  - A new iridoid glycoside, 6'-O-E-caffeoyl-mussaenosidic acid , in addition to one
      known aglycon, four known triterpenes and one known flavonoid, were isolated from
      the aerial parts of Scutellaria albida subsp. albida. Furthermore, 12 iridoids
      with similar structures isolated from Scutellaria sp., were examined for their
      inhibitory potency on lipoxygenase and lipid peroxidation, as well as their
      antioxidant activity, in comparison to known antioxidants e.g. caffeic acid,
      nordihydroguaretic acid (NDGA) and trolox. AAPH, DPPH and soybean lipoxygenase
      (LOX) assays were used for the tests. This investigation led to interesting
      observations considering the Structure-Activity Relationship. According to our
      results, the presence of a p-coumaroyl group optimized and even dramatically
      changed the biological responses of the investigated iridoids. 

PMID- 22630075
TI  - The integrated Michaelis-Menten rate equation: deja vu or vu jade?
AB  - A recent article of Johnson and Goody (Biochemistry, 2011;50:8264-8269) described
      the almost-100-years-old paper of Michaelis and Menten. Johnson and Goody
      translated this classic article and presented the historical perspective to one
      of incipient enzyme-reaction data analysis, including a pioneering global fit of
      the integrated rate equation in its implicit form to the experimental time-course
      data. They reanalyzed these data, although only numerical techniques were used to
      solve the model equations. However, there is also the still little known
      algebraic rate-integration equation in a closed form that enables direct fitting
      of the data. Therefore, in this commentary, I briefly present the integral
      solution of the Michaelis-Menten rate equation, which has been largely overlooked
      for three decades. This solution is expressed in terms of the Lambert W function,
      and I demonstrate here its use for global nonlinear regression curve fitting, as
      carried out with the original time-course dataset of Michaelis and Menten. 

PMID- 22630076
TI  - Synthesis and anticholinesterase activities of novel 1,3,4-thiadiazole based
      compounds.
AB  - In the present study, new (1,3,4-thiadiazol-2-yl)benzene-1,3-diol based compounds
      have been synthesized and their potential anticholinesterases properties have
      been investigated using the modified of Ellman's spectrophotometric method. The
      compounds were obtained by the reaction of hydrazides or thiosemicarbazides with
      aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]s. Their chemical
      structures were elucidated by IR, (1)H-NMR, (13)C-NMR and EI-MS spectral data and
      elemental analyses. Most of the compounds acted as acetylcholinesterase (AChE)
      and butyrylcholinesterase (BuChE) inhibitors in vitro, with IC50 values ranging
      from >500 to 0.053 MUM and from >500 to 0.105 MUM, respectively. The most potent
      compound 9 (IC50 = 0.053 MUM) proved to be selective toward AChE, exhibiting
      selectivity ratios versus BuChE of ca. 950. The kinetic studies showed that it is
      a mixed-type of AChE inhibitor. Another compound (2) was active against both
      enzymes with IC50 values in the low nM range. The structure-activity
      relationships (SARs) of the compounds under consideration were discussed.

PMID- 22630077
TI  - Subarachnoid anaesthetic blockade for sacral nerve stimulator insertion.

PMID- 22630078
TI  - Toxicity risk of nanocarriers.

PMID- 22630079
TI  - Context-dependent action of transforming growth factor beta family members on
      normal and cancer stem cells.
AB  - The transforming growth factor beta (TGFbeta) family embraces many growth factors
      including the Activins and bone morphogenetic proteins (BMPs). The pathways
      mediated by these growth factors are implicated in many fundamental biological
      processes such as early embryonic development, organ morphogenesis and adult
      tissue homeostasis and in a large number of pathologies including cancer. The
      action of these pathways is often contextual, which means that different cell
      types present different physiological responses to these ligands or that the
      response of one cell type to a certain ligand differs depending on the presence
      of other signaling proteins that stimulate the target cell together with
      TGFbeta/BMP. The latter usually reflects developmental stage or progression to a
      specific pathological stage. Not only diverse growth factors and cytokines can
      influence the response of tissues to TGFbeta/BMP, but a single cell type may also
      show drastically different physiological outcomes to TGFbeta or Activin signaling
      as compared to BMP signaling. This review describes differential physiological
      outcomes of TGFbeta and BMP signaling in normal embryonic or adult stem cells and
      eventually in cancer stem cells and the process of epithelial-mesenchymal
      transition. We also summarize evidence on the mechanistic antagonism between
      TGFbeta and BMP signaling as established in vascular differentiation and the
      progression of tissue fibrosis and cancer. The article ends by discussing
      possible advantages that the acquired knowledge of these signaling mechanisms
      offers to new regimes of cancer therapy and the ever-lasting problem of drug
      resistance elicited by tumor initiating cells.

PMID- 22630080
TI  - Deregulated bone morphogenetic protein receptor signaling underlies
      fibrodysplasia ossificans progressiva.
AB  - Transforming growth factor-beta family members, which include TGF-betas, activins
      and bone morphogenetic proteins (BMPs), play important roles in development and
      maintaining tissue homeostasis. The extracellular TGF-beta family members signal
      across the plasmamembrane by activating type I and type II serine/threonine
      kinase receptors. Pertubation in TGF-beta family receptor signaling has been
      implicated in certain diseases, including musculo-skeletal disorders.
      Fibrodysplasia ossificans progressiva (FOP) is a rare disorder characterized by
      progressive formation of ectopic bone and congenital malformations of the great
      toes. At present no curative therapy is available, therefore prevention of
      heterotopic ossification is the hallmark of FOP management. FOP has been linked
      to an autosomal dominant mutation on chromosome 2, to the gene encoding activin
      receptor-like kinase 2 (ALK2), a BMP type I receptor. This mutation is found in
      almost all classically affected FOP patients and causes the FOP phenotype. This
      discovery has paved the way for further investigations into the molecular basis
      underlying FOP and has recently pointed towards potential strategies to treat
      this devastating disease.

PMID- 22630081
TI  - The TGF-beta signaling pathway as a pharmacological target in a hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a cancer that usually develops on a liver
      already compromised by cirrhosis. Study of the underlying molecular mechanisms is
      essential so as to improve therapeutic strategies and to develop new
      pharmacological agents that may prevent or improve the course of this malignancy.
      Transforming growth factor-beta (TGF-beta) intervenes in the process of hepatic
      fibrogenesis and cirrhosis, two pathogenic preconditions for the formation and
      progression of HCC [1] [2]. In addition, TGF-beta plays a crucial role in the
      molecular pathogenesis of HCC and may, therefore, prove to be a promising drug
      target. We and other authors have recently demonstrated that inhibition of the
      TGF-beta signaling pathway results in a synergistic downstream action with an
      inhibitory effect on the progression of HCC. Several TGF-beta inhibitors have
      recently been developed, most of which are still in a preclinical phase, but they
      may soon be available for testing in patients with HCC. However, well-designed
      clinical trials will be needed to evaluate the effectiveness of these new agents
      prior to routine use in the clinic. Aim of this article is to make a brief review
      of the benefits and limitations of targeting the TGF-beta signaling pathway in
      HCC.

PMID- 22630082
TI  - TGF-beta: a master switch in tumor immunity.
AB  - The capacity of the immune system to distinguish foreign from self-antigen, and
      to subsequently eliminate the threat of disease without injuring the host is
      crucial for survival. It also serves to defend against tumor formation and
      progression via a process termed cancer immunosurveillance. Innate and adaptive
      immune cell types and effector molecules collectively function as extrinsic
      tumorsuppressor mechanisms. However, tumors may escape immunesurveillance through
      a variety of mechanisms that create a local microenvironment that is unfavorable
      for effective tumor immunity. Transforming growth factor beta (TGF-beta) has
      pleiotropic effects on the immune system, and is recognized as one of the most
      potent immunosuppressive agents in facilitating oncogenesis. The TGF-beta pathway
      promotes cancer progression by concomitantly enhancing tumor metastases while
      inhibiting the protective host immunity. In this review, we discuss mechanisms
      through which TGF-beta interferes with the development of an anti-tumor immunity
      and potential means through which to circumvent its activity in order to define
      more effective cancer immunotherapies.

PMID- 22630083
TI  - BMPS and liver: more questions than answers.
AB  - Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily and were
      first discovered as potent bone homeostasis regulators for their ability to
      induce endochondral bone formation, ectopic bone formation and fracture repair. A
      preeminent role of BMP signaling in developmental control of cell type
      specification, differentiation and organogenesis is also well established. More
      recently, a role for BMPs in adult tissue homeostasis has started being revealed.
      Thus, new studies show that BMPs regulate many cellular processes such as
      proliferation, apoptosis, differentiation and migration in many tissues and
      organs. As a consequence, dysregulation of BMP activity can have pathological
      consequences, and there is mounting evidence for the involvement of BMPs in
      different human diseases. In this review, we have focused on summarizing the
      present knowledge on the relevance of BMPs in liver physiology and
      pathophysiology, from the well-recognized role in liver development to the
      emerging contribution to the function and dysfunction of the adult liver. While
      no doubts seem to rise about the regulatory activities of BMPs on metabolic
      pathways in the liver, potential pro- and anti-fibrogenic and tumorigenic actions
      will likely be a matter of debate during coming years. Collectively, the work
      here presented provides the basis to consider BMPs as potential targets of
      intervention in liver diseases.

PMID- 22630084
TI  - Cellular players in lung fibrosis.
AB  - Pathogenic mechanisms involved in fibrosis of various organs share many common
      features. Myofibroblasts are thought to play a major role in fibrosis through
      excessive deposition of extracellular matrix during wound healing processes.
      Myofibroblasts are observed in fibrotic lesions, and whereas these derive from
      the hepatic stellate cells in liver, in lung they appear to originate from
      fibroblasts. The source of these fibroblasts has been the object of numerous
      studies over the recent years and points towards multiple sources. First of all,
      resident fibroblasts are thought to differentiate into the more contractile
      myofibroblasts, secreting many extracellular matrix proteins. Secondly, the
      epithelial to mesenchymal transition (EMT) of epithelial cells may also account
      for increased numbers of fibroblasts, though in vivo evidence in patient tissue
      is still scarce. Thirdly, the enigmatic fibrocytes, stemming from the bone
      marrow, may also account for increasing numbers of fibroblasts in fibrotic
      lesions. These pathogenic processes are further augmented by the generation of so
      called alternatively activated macrophages, which have direct and indirect
      effects on myofibroblast accumulation and collagen deposition. TGFbeta, which is
      produced predominantly by macrophages, plays a central role in all these
      processes by inducing EMT, driving differentiation of fibrocytes, and
      differentiation towards myofibroblasts. This review describes the potential
      origins and roles of these fibrotic cells in the lung and discusses models to
      study these cells in vitro. These models offer innovative approaches in target
      and drug discovery, aiming to uncover novel therapeutic targets that regulate the
      profibrotic phenotype of these cells.

PMID- 22630085
TI  - TGFbeta signaling in liver regeneration.
AB  - Adult organ regeneration occurs in many systems such as in liver, skin, intestine
      and heart, indicating that postnatal life is not a static or quiescent state but
      a dynamic and complex process. The liver is a spectacular organ, exhibiting high
      regenerative capacity crucial for homeostasis and tissue repair: injuries induced
      mechanically or chemically, can be completely restored. Regeneration involves
      extensive cell division, inflammation and extracellular matrix remodeling
      processes. At the molecular level, one of the key mediators of regeneration
      response is the secreted cytokine transforming growth factor-beta (TGFbeta).
      TGFbeta is a profibrogenic and anti-proliferative protein with pleiotropic
      functions depending on the cellular context. In this review, we discuss the role
      of TGFbeta in the development of the liver and in adult liver regeneration, with
      particular emphasis on its role in regulation of hepatocyte regeneration and in
      hepatic progenitor cell-induced regeneration. Finally, we give an overview of the
      current direction of liver research towards cell replacement therapies.

PMID- 22630086
TI  - TGF-beta inihibitor-loaded polyelectrolyte multilayers capsules for sustained
      targeting of hepatocarcinoma cells.
AB  - In this review we will report on recent advanced in polyelectrolyte capsules for
      targeted drug delivery (eg of growth factor inhibitor) against epatocarcinoma.
      Degradable polyelectrolyte multilayers capsules (PMCs) are of particular interest
      for cancer therapy since under physiological conditions they can be enzymatically
      degraded upon cell interaction. Small bioactive molecules such as TGF-Beta
      inhibitors can be incorporated inside them. Nano-to-microscale delivery systems
      can enhance efficacy at single cell level for targeted therapy. Layer-by-layer
      (LbL) self-assembled capsules are novel carriers maximizing drug administration
      and improving antimetastatic activity of TGF-Beta inhibitors in Hepatocellular
      Carcinoma (HCC).

PMID- 22630087
TI  - TGF-beta in epithelial to mesenchymal transition and metastasis of liver
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) represent
      the majority of hepatic malignancies and are among the most frequent causes of
      cancer deaths worldwide with a rising incidence in western countries. Upon
      progression of liver cancer, the epithelial to mesenchymal transition (EMT) is
      considered a key process that drives intrahepatic metastasis. EMT is the
      transformation of epithelial cells to a mesenchymal phenotype exacerbating
      motility and invasiveness of various epithelial cell types. In this review we
      focus on EMT in hepatic fibrosis, HCC and CCC that is governed by the
      transforming growth factor (TGF)-beta signaling. This cytokine has been shown to
      play diverse and conflicting roles in malignant development, acting as a tumor
      suppressor in early cancerogenesis but enhancing tumor dissemination in later
      stages of tumor progression. Importantly, TGF-beta can induce EMT in a variety of
      cancers including HCC and CCC, even though the complex molecular mechanisms
      underlying this process are not yet fully understood. We aim at collecting recent
      findings on the impact of TGF-beta-induced EMT in liver carcinoma progression and
      at discussing new insights on promising drugable targets for future therapeutic
      approaches against CCC and HCC.

PMID- 22630088
TI  - Editorial: TGF-beta1 in pre-malignant and malignant liver disease.

PMID- 22630089
TI  - Stem cells research for reprogramming the female fertility.

PMID- 22630090
TI  - Issue of transparency in stem cell therapy.

PMID- 22630091
TI  - Efficacy of single dose perioperative intravenous steroid (dexamethasone) for
      postoperative pain relief in tonsillectomy patients.
AB  - OBJECTIVE: To determine the efficacy of single dose perioperative intravenous
      steroid (dexamethasone) for postoperative pain relief in patients undergoing
      tonsillectomy. STUDY DESIGN: Quasi-experimental study. PLACE AND DURATION OF
      STUDY: Combined Military Hospital, Lahore, from November 2009 to June 2010.
      METHODOLOGY: Sixty patients were divided into two equal groups. A single dose of
      dexamethasone was given to patients of group A during induction of anaesthesia,
      whereas no steroid was given to the patients in group B. Postoperative pain
      scores were assessed at 2, 6 and 12 hours in both groups using visual analogue
      scale (VAS). Pain was classified as mild (0-3), moderate (4-7) and severe (8-10)
      on visual analogue scale. RESULTS: There was no significant difference in pain
      scores after 2 hours postoperatively. Pain scores of Group A at 6 and 12 hours
      postoperatively were found to be significantly low than Group B. CONCLUSION:
      Single dose perioperative intravenous injection of dexamethasone in tonsillectomy
      patients reduces postoperative tonsillectomy pain.

PMID- 22630092
TI  - Paraffin-based immunohistochemistry in the evaluation of glomerular diseases in
      renal biopsies.
AB  - OBJECTIVE: To determine sensitivity and specificity of paraffin-based
      immunohistochemistry in the evaluation of glomerular diseases in renal biopsies
      using immunofluorescence as gold standard. STUDY DESIGN: Cross-sectional
      analytical study. PLACE AND DURATION OF STUDY: Department of Histopathology,
      Armed Forces Institute of Pathology, Rawalpindi, from August 2008 to August 2009.
      METHODOLOGY: Seventy renal biopsy specimens fulfilling the inclusion criteria for
      light microscopy and immunofluorescence during the study period were evaluated.
      Antibodies to immunoglobulins (IgG, IgA, and IgM) and components of complement
      system (C3) were applied on 70 formalin-fixed paraffin-embedded renal biopsy
      specimens previously classified by means of light microscopy and
      immunofluorescence (IF). Staining for these antibodies was recorded as positive
      and negative for immunohistochemistry (IHC) and IF in paired proportions
      presuming IF as gold standard test. The sensitivity, specificity, positive
      predicitive value and negative predicitive value of individual antibody were
      calculated. RESULTS: Of 70 patients, mean age was 33 +/- 18 years ranging from 2
      to 80 years. Forty five (64%) were males and 25 (36%) were females. The
      sensitivity, specificity and predictive values of individual antibodies to IgG,
      IgA, IgM and C3 were very low and generally in the range of 40 - 60%. CONCLUSION:
      The sensitivity, specificity and predictive values of immunohistochemistry on
      formalin-fixed paraffin-embedded renal biopsy specimens were very low and
      therefore, not suitable for evaluation of renal biopsies in current
      circumstances.

PMID- 22630093
TI  - Activity of beta-lactam beta-lactamase inhibitor combinations against extended
      spectrum Beta-lactamase producing Enterobacteriaceae in urinary isolates.
AB  - OBJECTIVE: To determine the susceptibility pattern of beta-lactam beta-lactamase
      inhibitor combinations against extended-spectrum beta-lactamase (ESBL) producing
      Enterobacteriaceae in urinary isolates. STUDY DESIGN: Observational study. PLACE
      AND DURATION OF STUDY: Ziauddin University Hospital, Karachi, from February to
      October 2008. METHODOLOGY: A total of 190 consecutive non-duplicate isolates of
      ESBL producing Enterobacteriaceae from urine samples of in-patients were included
      in the study. Urinary samples from out-patients, repeat samples and non-ESBL
      producing isolates were excluded. Detection of ESBL was carried out by double
      disk diffusion technique. Antimicrobial susceptibility testing was performed
      using modified Kirby Bauer's disk diffusion method according to CLSI guidelines.
      Statistical analysis was performed by SPSS version 10. RESULTS: Of the 190 ESBL
      isolates tested, 88 cases (46.31%) were sensitive and 6 cases (3.15%) were
      resistant to all three combinations, the rest 96 cases (50.52%) were resistant to
      at least one of the combinations. Susceptibility pattern of
      cefoperazone/sulbactam, piperacillin/tazobactam, and amoxicillin/clavulanic acid
      was 95.26, 92.10, and 44.31 percent respectively. CONCLUSION:
      Cefoperazone/sulbactam exhibited the best activity against ESBL producing
      Enterobacteriaceae followed by piperacillin/tazobactam. Hospital antibiotic
      policies should be reviewed periodically to reduce the usage of extended spectrum
      cephalosporins and replace them with beta-lactam beta-lactamase inhibitor
      combinations agent for treating urinary tract infections.

PMID- 22630094
TI  - Intravitreal bevacizumab in central serous chorioretinopathy.
AB  - OBJECTIVE: To evaluate the effect of intravitreal bevacizumab injection in
      patients with central serous chorioretinopathy (CSCR). STUDY DESIGN: Quasi
      experimental study. PLACE AND DURATION OF STUDY: Layton Rehmatullah Benevolent
      Trust Eye and Cancer Hospital, Lahore, from July 2010 to April 2011. METHODOLOGY:
      There were 43 eyes of 32 adult patients with CSCR. Patients with choroidal
      neovascularization, prior treatment for CSCR, history of thromboembolism,
      intraocular pressure more than 21 mmHg, history of retinal detachment,
      intraocular inflammation, and allergy to fluorescence were excluded from study.
      All patients had intravitreal injection of off label bevacizumab. At baseline and
      follow-up visits, patients had best corrected visual acuity (BCVA) and central
      macular thickness (CMT) measurement with optical coherence tomography. They were
      followed-up for 6 months. Outcome measures included BCVA and CMT. Wilcoxon Signed
      Ranks test was used for evaluation of BCVA and CMT. RESULTS: There were 26
      (81.3%) males and 6 (18.7%) females with 21 (65.5%) cases of unilateral and 11
      (34.5%) cases of bilateral involvement. Mean age was 39.09 +/- 8.49 years.
      Nineteen (59.4%) eyes showed less than 6 months involvement and 13 (40.6%) eyes
      showed more than 6 months involvement. Mean number of injections required was
      2.37 +/- 1.24 in acute cases and 3.05 +/- 1.39 in chronic cases. Overall mean of
      required injections was 2.67 +/- 1.34. Median visual acuity at baseline was 0.25
      and at 6 months was 0.7 (p < 0.001). Median CMT at baseline was 557 MU and at 6
      months was 286 MU (p < 0.001). CONCLUSION: Intravitreal bevacizumab injection was
      associated with visual improvement and reduced neurosensory detachment.

PMID- 22630095
TI  - Visual outcome of pars plana vitrectomy for dropped nucleus after
      phacoemulsification.
AB  - OBJECTIVE: To determine the visual outcome of patients who underwent pars plana
      vitrectomy for dropped nucleus after phacoemulsification. STUDY DESIGN:
      Interventional case series. PLACE AND DURATION OF STUDY: LRBT Free Base Eye
      Hospital, Karachi, from February 2008 to January 2011. METHODOLOGY: Forty-eight
      eyes of forty eight patients having history of dropped nucleus (soft remnant,
      half nucleus or complete nucleus) underwent 20 gauge pars plana vitrectomy within
      24 days of phacoemulsification. After complete vitrectomy nucleus was lifted with
      the help of perfluorocarbon and removed either through a limbal incision or by
      using phacofragmenter, whereas small lens remnants were removed with a vitreous
      cutter. Intraocular lens was implanted at the end of surgery. Postoperative
      visual acuity, and any complications were assessed. Patients were followed for a
      period of 12 months. RESULTS: Final visual acuity ranged from 6/9 to 6/18 in 34
      eyes (70.83%), 6/24 to 6/36 in 8 eyes (16.66%) and 6/60 or less in 6 of 48 eyes
      (12.5%). Complications included raised intraocular pressure in 6 eyes (12.5%) and
      retinal detachment in 2 eyes (4.1%), corneal oedema and decompensation in 3 eyes
      (6.25%) and cystoids macular oedema in 4 cases (8.33%) out of 48 cases.
      CONCLUSION: The loss of crystalline lens in the vitreous during
      phacoemulsification is a severe complication, but appropriate and timely
      management can restore good visual outcome and minimize complications.

PMID- 22630096
TI  - Effect of glycemic conrol on periodontal status.
AB  - OBJECTIVE: To assess the association between glycemic control and the periodontal
      status of an urban population with poor oral hygiene. STUDY DESIGN: Cross
      sectional study. PLACE AND DURATION OF STUDY: Memon Dental Care Centre and Memon
      Diabetic and Diagnostic Centre, Karachi, from July to December 2010. METHODOLOGY:
      One hundred and forty-one individuals with controlled diabetes and 143 with
      uncontrolled diabetes were recruited from the dental clinic. All underwent
      clinical examination and grades on plaque index, gingival index, periodontal
      index and calculus index were recorded and compared. RESULTS: The group with
      uncontrolled diabetes included 56 males (38.9%) and 88 females (61.1%), and the
      controlled diabetic group included 49 males (34.8%) and 92 females (65.2%).
      Periodontal index, gingival index and plaque index showed significant differences
      in both the groups (p-value < 0.016, < 0.001, < 0.002, respectively) while the
      difference of calculus was not significant i.e. 0.056. The mean number of teeth
      present in both the groups was 22. Most of the subjects cleaned their teeth once
      daily with the help of tooth brush, while the patients brushing twice daily were
      16%. CONCLUSION: Uncontrolled diabetes had significantly severe impact on
      periodontal status in the studied groups with poor oral hygiene; diabetic
      patients have more number of missing teeth, and more plaque.

PMID- 22630097
TI  - Lip line preference for variant face types.
AB  - OBJECTIVE: To determine the effect of altered lip line on attractiveness and to
      find preferred lip line for vertical face types in both genders. STUDY DESIGN:
      Cross-sectional analytical study. PLACE AND DURATION OF STUDY: The Aga Khan
      University Hospital, Karachi, from May to July 2009. METHODOLOGY: Photographs of
      two selected subjects were altered to produce three face types for the same
      individual with the aim of keeping the frame of the smile constant. Lip line was
      then altered for both the subjects as: both dentitions visible, upper incisors
      visible, upper incisors and 2 mm gum and 4 mm gum visible. The pictures were
      rated by different professionals for attractiveness. Descriptive statistics for
      the raters and multiple factor ANOVA was used to find the most attractive lip
      line. RESULTS: The total number of raters was 100 with the mean age of 30.3 +/- 8
      years. The alterations in the smile parameters produced statistically significant
      difference in the attractiveness of faces, whereas the perception difference was
      found to be insignificant amongst raters of different professions. Preferred lip
      line was the one showing only the upper incisors in dolico and mesofacial male
      and female genders whereas 2 mm gum show was preferred in brachyfacial subjects.
      CONCLUSION: The variability in lip line showed significant difference in the
      perceived attractiveness. Preferred lip lines as the one showing only the upper
      incisors in dolico and mesofacial male and female genders whereas 2 mm gum show
      was preferred in brachyfacial subjects.

PMID- 22630098
TI  - Profile of acute carbon monoxide poisoning in the west province of Iran.
AB  - OBJECTIVE: To document the epidemiology and risk factors of acute carbon monoxide
      (CO) poisoning in the west of Iran and specify potentially presentable
      characteristics. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY:
      Imam Khomeini Hospital of Kermanshah, Iran, from July 2006 to March 2008.
      METHODOLOGY: This study was conducted using the records of 143 cases of CO
      poisoning referred to the only centre for the reference of poisoning cases.
      Intent, age groups, source of poisoning and clinical presentation were noted and
      described as frequency. RESULTS: One-hundred forty two cases (99.3%), were
      accidental and only one case (0.7%) was suicidal. Mortality was (21.7%, n=31).
      The highest mortality was found in the age groups of 20-30 years and below 10
      years. The greatest frequency happened in autumn and winter. The clinical
      symptoms and manifestations of CO poisoning included headache (35.3%), nausea
      (25.4%), vomiting (21%), dyspnea (10.3%), and decrease in level of consciousness
      (8%). Gas water heaters (35%), room heaters (32%), stoves (24%) and other items
      (9%) were the principal sources of the individuals' exposure to CO. CONCLUSION:
      CO poisoning is a serious public health problem in west of Iran (Kermanshah). The
      number of CO poisoning cases was highest in the colder seasons of the year,
      whereas the majority of the poisoning cases could be prevented.

PMID- 22630099
TI  - Surgical handover in an era of reduced working hours: an audit of current
      practice.
AB  - OBJECTIVE: To examine the current practice of handover and to record trainees'
      assessment of handover process. STUDY DESIGN: An audit study. PLACE AND DURATION
      OF STUDY: Department of General Surgery, Scarborough General Hospital,
      Scarborough, United Kingdom, from January to April 2010. METHODOLOGY: A paper
      based questionnaire containing instruments pertaining to handover guidelines was
      disseminated to trainees on surgical on-call rota at the hospital. Trainees'
      responses regarding handover process including information transferred,
      designated location, duration, structure, senior supervision, awareness of
      guidelines, formal training, and rating of current handover practice were
      analysed. RESULTS: A total of 42 questionnaires were returned (response rate =
      100%). The trainees included were; registrars 21% (n=9), core surgical trainees
      38 % (n=16), and foundation trainees 41% (n=17). Satisfactory compliance (> 80%
      handover sessions) to RCS guidelines was observed for only five out of nine
      components. Ninety-five percent of hand over sessions took place at a designated
      place and two-third lasted less than 20-minutes. Computer generated handover
      sheet 57% (n=24) was the most commonly practised method of handover. Specialist
      registrar 69 % (n=29) remained the supervising person in majority of handover
      sessions. None of the respondents received formal teaching or training in
      handover, whereas only half of them 48% (n=20) were aware of handover guidelines.
      Twenty-one percent of the trainees expressed dissatisfaction with the current
      practice of handover. CONCLUSION: Current practice of surgical handover lacks
      structure despite a fair degree of compliance to RCS handover guidelines. A
      computerised-sheet based structured handover process, subjected to regular audit,
      would ensure patient safety and continuity of care.

PMID- 22630100
TI  - Calcification of the lateral collateral ligament of the knee: a rare cause of
      acute knee pain.
AB  - Calcification of the lateral collateral ligament is a rare phenomenon, which can
      cause acute knee pain. The management is usually conservative and there is
      subsequent resolution of the calcification seen on initial radiographs. It is
      important to exclude more sinister pathology such as septic arthritis as a cause
      of pain. We report the case of an elderly lady who presented with acute knee
      pain. Initial radiographs showed calcification at the lateral aspect of the knee
      joint. The pain settled with conservative management. Resorption of calcification
      was demonstrated on subsequent radiographs.

PMID- 22630101
TI  - Courvoisier's law revisited.
AB  - According to Courvoisier's law; if gallbladder is palpable in a jaundiced
      patient, it is unlikely to be due to gallstones, because stones would have given
      rise to chronic inflammation and subsequently fibrosis of gallbladder therefore,
      rendering it incapable of dilatation. Conversely, the causes other than stone
      (principally tumours), would result in the distension of gallbladder, felt on
      abdominal palpation. However, in Courvoisier study of 109 cases of dilatation of
      gallbladder, 17 were due to impacted stones. Therefore, Courvoisier concluded
      that dilatation of gallbladder was rare with stones obstructing the common bile
      duct. Despite this fact it is always assumed that the palpable gallbladder is due
      to malignancy (pancreatic or periampullary etc.). Here, we report a rare case of
      palpable gallbladder in a jaundiced patient due to multiple cholelithiasis and a
      large choledocholithiasis causing obstruction of CBD.

PMID- 22630102
TI  - Duhamel's procedure for adult Hirschsprung's disease.
AB  - An adult presented with chronic constipation and abdominal mass. Clinical
      features, abdominal radiographs and barium enema revealed features consistent
      with Hirschsprung's disease. Full-thickness rectal biopsy was planned, but
      patient was lost to follow-up and presented 3 years later with intestinal
      obstruction. Exploratory laparotomy with resection of affected sigmoid colon and
      end colostomy were performed. Sequential rectal biopsies were obtained during the
      procedure to confirm the diagnosis. Later, Duhamel's procedure with a diverting
      loop ileostomy was successfully performed. Ileostomy reversal was done
      thereafter. There was complete resolution of symptoms and dramatic improvement in
      bowel function.

PMID- 22630103
TI  - Posterior reversible encephalopathy syndrome.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuro
      radiological entity may develop in patients with pre-eclampsia, eclampsia or
      delayed postpartum eclampsia, immunological conditions and with certain anti
      neoplastic agents. This case report describes about a patient with pregnancy
      induced hypertension who developed PRES postnatally. Early recognition and
      treatment prevented serious morbidity.

PMID- 22630104
TI  - Development of massive pneumopericardium after intubation and positive pressure
      ventilation.
AB  - Pneumopericardium is a rare complication of chest trauma, mechanical ventilation
      and cavitating pneumonia. We report a case of a 7-year-old patient with chronic
      myeloid leukemia who developed massive pneumopericardium immediately after being
      electively intubated for a diagnostic radiological procedure in the setting of
      ongoing Enterococcal pneumonia. As intensive care medicine becomes more prevalent
      in hospitals, we believe that clinicians need to be aware of this uncommon but
      potentially fatal condition.

PMID- 22630105
TI  - Lymphadenopathic Kaposi's sarcoma in an immunocompetent adult.
AB  - Kaposi's sarcomas (KS) are vascular lesions which usually originate from multiple
      sites in the mid-dermis extending to the dermis. The aetiology is unknown, but
      infection from human herpes virus type 8 has been suggested. Several reports of
      KS had come from Africa initially and from worldwide later due to the close
      association with HIV/AIDS. Prior to this however, KS was very frequent in Eastern
      Europe, Italy and the United States where it existed in an indolent form in the
      elderly men of Jewish ancestry. KS may also be due to iatrogenic immune
      suppression from chronic use of steroids, elevated degree of expression of
      numerous cytokines and angiogenic growth factors including TNF alpha, IL-6, bFGF,
      HIVtat protein and oncostatin M. Lymphadenopathic KS involves the lymph-nodes,
      viscera and the gastrointestinal tract and may run a disseminated and aggressive
      course. We are reporting one such case in an immunocompetent male.

PMID- 22630106
TI  - A case of atypical idiopathic choroidal effusion syndrome.
AB  - Uveal effusion syndrome is characterized by annular ciliochoroidal detachment,
      shifting non-rhegmatogenous retinal detachment, unremarkable inflammation in the
      anterior eye segment and normal intraocular pressure. A 36-year-old Caucasian
      hypermetropic male presented in the eye casualty with a week history of curtain
      like effect in front of his left eye associated with worsening of vision and
      flashing lights. Left fundus examination revealed retinal detachment with smooth
      shaped elevation superonasaly and detached retina inferiorly confirmed on
      ultrasound B-scan with no tobacco dust in the anterior vitreous. Diagnosis of
      uveal effusion syndrome was made. Lamellar sclerectomies in the two quadrants
      were performed. Fourteen months postoperatively, the left eye choroidal effusion
      gradually settled down and at 18 months the retina flattened. Early diagnosis,
      close follow-up, and appropriate management are mandatory to improve or maintain
      visual function in such patients.

PMID- 22630107
TI  - Profound hypernatremia due to central diabetes insipidus.
AB  - Diabetes insipidus is a rare endocrine disorder in paediatric patients. Polyuria
      is a cardinal manifestation that is extremely difficult to recognize in diapered
      infants. Careful urine quantification is the key to diagnosis in appropriate
      clinical setting. We report a case of a 4 months old infant presenting with an
      acute life threatening event following an episode of vomiting and decreased oral
      intake. She had profound hypernatremia which persisted after stabilization.
      Polyuria unrecognized by the mother was revealed by 24-hour urine output
      measurement. A diagnosis of diabetes insipidus was made after appropriate
      laboratory investigations including serum and urine osmolality. The central
      nature of the disease was confirmed by neuroimaging which showed
      holoprosencephaly.

PMID- 22630109
TI  - Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome (CdLS) is a rarely seen multisystem developmental
      disorder syndrome characterized by facial dysmorphia (arched eyebrows, synophrys,
      depressed nasal bridge, long philtrum, down-turned angles of the mouth), upper
      extremity malformations, hirsutism, cardiac defects, growth and cognitive
      retardation, and gastrointestinal abnormalities. We present here a case of
      newborn male who presented with the complaints of feed regurgitation, choking and
      cyanosis. There was a distinct facial dysmorphism with arched and bushy eyebrows,
      long philtrum, thin upper lip, depressed nasal bridge and hirsutism. The patient
      was diagnosed as having Cornelia de Lange syndrome on the recognition of
      distinctive facial features in addition to the pre- and postnatal growth
      retardation, feeding problems and physical malformations including limb defects.

PMID- 22630110
TI  - Elective tracheostomy in mechanically ventilated children.
AB  - Tracheostomy is an important procedure in children requiring prolonged mechanical
      ventilation. We conducted a retrospective study to assess the frequency,
      indications, postoperative course and short-term outcome of elective tracheostomy
      in a Paediatric Intensive Care Unit (PICU) of Pakistan. Twenty-five patients
      underwent tracheostomy in last 5 years (2.2 % of all PICU admissions). Mean age
      of patients was 6 years and 60% were male. The most common indication for
      tracheostomy was prolonged mechanical ventilation secondary to neurological
      disease (60%), followed by upper airway obstruction (40%). Major complications
      included accidental decannulation (20%) and tube obstruction (20%). Three
      patients (12%) developed ventilator-associated pneumonia after tracheostomy
      change while persistent bacterial colonization of trachea was observed in 8
      patients (32%). Decannulation was achieved in 40% (10/25). There was no mortality
      related to tracheostomy in this series.

PMID- 22630111
TI  - Stress level in medical students.

PMID- 22630112
TI  - Injuries increase the amputee burden at the prosthesis centre: a 2-year
      retrospective survey of amputees in a low-income setting.
AB  - The aim of this study is to survey different types of injuries as the cause for
      prosthesis fitting in the Institute of Physical Medicine and Rehabilitation
      (IPM&R). This retrospective chart review was conducted at the IPM&R at the Dow
      University of Health Sciences, from the year 2007 till 2009. We selected all
      amputees who got enrolled in our institute for prosthesis fitting with major
      amputations, during the above mentioned period of time. Informed verbal consent
      was taken from each patient before recording their data at the IPM&R. Anonymity
      has been maintained. Data for this study was collected through a structured
      questionnaire, variables included: gender, age, town of origin, cause of
      amputation, level of amputation, limb involvement (unilateral or bilateral),
      level and causes of amputations. The data entry and analysis were done on SPSS
      (Statistical Package of Social Sciences) version 16.0. Of the amputee burden of
      our study, 55.9% was due to trauma, which is a preventable cause of disability.
      This is mostly affecting men in the productive age group. New strategies need to
      be devised in order to alleviate the burden of amputations resulting from
      preventable injuries.

PMID- 22630113
TI  - Cost-effectiveness of partially-hydrolyzed formula for prevention of atopic
      dermatitis in Australia.
AB  - OBJECTIVE: To perform an economic evaluation of a specific brand of partially
      hydrolyzed infant formula (PHF-W) in the prevention of atopic dermatitis (AD)
      among Australian infants. METHODS: A cost-effectiveness analysis was undertaken
      from the perspectives of the Department of Health and Aging (DHA), of the family
      of the affected subject and of society as a whole in Australia, based on a
      decision-analytic model following a hypothetical representative cohort of
      Australian newborns who are not exclusively breastfed and who have a familial
      history of allergic disease (i.e., are deemed 'at risk'). Costs, consequences,
      and incremental cost-effectiveness ratios (ICER) were calculated for PHF-W vs
      standard cow's milk based infant formula (SF), and, in a secondary analysis, vs
      extensively hydrolyzed infant formula (EHF-Whey), when the latter was used for
      the prevention of AD. RESULTS: From a representative starting cohort of 87,724
      'at risk' newborns in Australia in 2009, the expected ICERs for PHF-W vs SF were
      AU$496 from the perspective of the DHA and savings of AUD1739 and AU$1243 from
      the family and societal perspectives, respectively. When compared to EHF-Whey,
      PHF-W was associated with savings for the cohort of AU$5,183,474 and AU$6,736,513
      from the DHA and societal perspectives. LIMITATIONS: The generalizability and
      transferability of results to other settings, populations, or brands of infant
      formula should be made with caution. Whenever possible, a conservative approach
      directing bias against PHF-W rather than its comparators was applied in the base
      case analysis. Assumptions were verified in one-way and probabilistic sensitivity
      analyses, which confirmed the robustness of the model. CONCLUSIONS: PHF-W appears
      to be cost-effective when compared to SF from the DHA perspective, dominant over
      SF from the other perspectives, and dominant over EHF-Whey from all perspectives,
      in the prevention of AD in 'at risk' infants not exclusively breastfed, in
      Australia.

PMID- 22630114
TI  - Congruency effects in conceptualizing for speech.
AB  - In naming a picture at the basic level, a semantically related distractor word
      induces interference in comparison to an unrelated word. When the task is changed
      from basic-level naming to categorization, however, this effect reverses to
      semantic facilitation. In previous studies, this semantic facilitation effect was
      attributed to "message congruency" at the conceptual level. The present study
      examines the nature of this message congruency effect: Is it due to competition
      between two activated category concepts in the incongruent condition or is it due
      to convergence of activity on a single category concept in the congruent
      condition? Two experiments show that neither the strength with which the context
      stimulus activates an incongruent category concept nor the semantic distance
      between the category concepts activated by target and distractor affect target
      categorization speed. We conclude that the message congruency effect is most
      likely due to convergence on a single category concept in the category-congruent
      condition.

PMID- 22630115
TI  - Prognosis analysis and risk factors related to progressive intracranial
      haemorrhage in patients with acute traumatic brain injury.
AB  - BACKGROUND: Since progressive intracranial haemorrhage (PIH) was introduced in
      neurosurgical literatures, several studies have been performed. PIH has been
      shown to be associated with a high increase in the risk of clinical worsening and
      related to morbidity and mortality as well. So, early detection and prediction of
      PIH is practically important in a clinical situation. OBJECTIVES: To investigate
      the risk factors related to PIH in patients with acute traumatic brain injury
      (TBI) and analyse their clinical significances. METHODS: PIH was confirmed by
      comparing the first and repeated CT scans. Data compared included gender, age,
      mechanism of injury, Glasgow Coma Score (GCS) at admission, timing from injury to
      the first CT, the signs of the initial CT scan, prothrombin time (PT), activated
      partial thromboplastin time (APTT), fibrinogen (Fg), thrombin time (TT), platelet
      (PLT) and D-dimer (D-D) values. Logistic regression analysis was used to show the
      risk factors related to PIH. RESULTS: A cohort of 498 patients with TBI was
      evaluated, and there were 139 (27.91%) patients who suffered from PIH. The
      differences between PIHs and non-PIHs were significant in age, GCS at admission,
      the signs of the initial CT scan (fracture, subarachnoid haemorrhage, brain
      contusion and primary haematoma), PT, Fg and D-D values (p < 0.001). Logistic
      regression analysis was used to identify that CT scans (subarachnoid haemorrhage,
      brain contusion and primary haematoma) and plasma D-D values as the most
      important predictors of PIH (p < 0.001). CONCLUSIONS: For patients with the
      initial CT scan showing subarachnoid haemorrhage, brain contusion and primary
      haematoma with abnormal D-D levels, an earlier and dynamic CT scan should be
      performed, for the detection of PIH as early as possible and the medical
      intervention would be enforced in time.

PMID- 22630116
TI  - Biopolymeric mucoadhesive bilayer patch of pravastatin sodium for buccal delivery
      and treatment of patients with atherosclerosis.
AB  - Mucoadhesive bilayer buccal patch has been developed to improve the
      bioavailability and therapeutic efficacy along with providing sustained release
      of pravastatin sodium. Buccal patches comprising of varying composition of
      Carbopol 934P and HPMC K4M were designed and characterized for surface pH,
      swelling index, in vitro bioadhesion, mechanical properties, in vitro drug
      release and in vivo pharmacokinetic and pharmacodynamics performance. All
      formulations exhibited satisfactory technological parameters and followed non
      fickian drug release mechanism. Bilayer buccal patch containing Carbopol 934P and
      HPMC K4M in 4:6 ratio (PBP5) was considered optimum in terms of swelling,
      mucoadhesion, mechanical properties and in vitro release profile. Pharmacokinetic
      studies in rabbits showed significantly higher (p < 0.05) Cmax (75.63 +/- 6.98
      ng/mL), AUC(0-8) (311.10 +/- 5.89 ng/mL/h) and AUC(0-infinity) (909.42 +/- 5.89
      ng/mL/h) than pravastatin oral tablet (Cmax - 67.40 +/- 9.23 ng/mL, AUC(0-8)
      130.33 +/- 10.25 ng/mL/h and AUC(0-infinity)-417.17 +/- 5.89 ng/mL/h)). While,
      increased tmax of buccal patch indicated its sustained release property in
      comparison to oral tablet. Pharmacodynamic studies in rabbits showed
      statistically significant difference (p < 0.005) in the reduction of TG (131.10
      +/- 10.23 mg/dL), VLDL (26.00 +/- 2.56 mg/dL) and LDL level (8.99 +/- 3.01 mg/dL)
      as compared to oral conventional tablet. In conclusion, bioavailability from the
      developed buccal patch of pravastatin was 2.38 times higher than the oral dosage
      form, indicating its therapeutic potential in the treatment of atherosclerosis.

PMID- 22630117
TI  - Abstracts: Tenth Conversation.

PMID- 22630121
TI  - The Journal of Biomolecular Structure and Dynamics Establishes Web Site: The JBSD
      WWW Edition.

PMID- 22630122
TI  - Cancer Watch Establishes Web Site: The CANCER WATCH WWW Edition.

PMID- 22630123
TI  - Peptide signaling molecules: ancient signal and functional diversity.

PMID- 22630124
TI  - The roles of neuropeptides in Caenorhabditis elegans including their importance
      in the regulation of feeding and metabolism.
AB  - C. elegans has 302 neurons (in the adult hermaphrodite) and this simple nervous
      system harbours over 250 neuropeptides. Neuropeptides are a class of signalling
      molecule implicated in key physiological roles and thus confer a surprising level
      of complexity to signalling in this nematode. Indeed, it is probable that most,
      if not all, sensory, motor and interneurons, in C. elegans synthesise and release
      at least one neuropeptide but that many neurons synthesise an array of
      neuropeptides. In this review neuropeptides and their receptors with specific
      roles in feeding, metabolism, reproduction and locomotion are discussed. It is
      noted that the majority of C. elegans neuropeptides do not yet have defined roles
      and their cognate receptors have not yet been identified. Future studies will
      serve to provide further fundamental insight into how neuropeptide signalling can
      underpin animal behaviour.

PMID- 22630125
TI  - Invertebrate FMRFamide related peptides.
AB  - In 1977 the neuropeptide FMRFamide was isolated from the clam, Macrocallista
      nimbosa. Since then several hundred FMRFamide-related peptides (FaRPs) have been
      isolated from invertebrate animals. Precursors to the FaRPs likely arose in the
      cnidarians. With the transition to a bilateral body plan FaRPs became a fixture
      in the invertebrate phyla. They have come to play a critical role as
      neurotransmitters, neuromodulators, and neurohormones. FaRPs regulate a variety
      of body functions including, feeding, digestion, circulation, reproduction,
      movement. The evolution of the molecular form and function of these omnipresent
      peptides will be considered.

PMID- 22630126
TI  - Multifunctional role of PACAP-like peptides in molluscs.
AB  - The purpose of this review is to highlight the role of pituitary adenylate
      cyclase-activating polypeptide (PACAP) in a range of physiological and behavioral
      processes of gastropod molluscs, Helix and Lymnaea. Since its discovery in 1989
      PACAP has become increasingly recognized for its important and diversified roles
      in the central and peripheral nervous system and in several peripheral organs of
      a variety of vertebrate and invertebrate species. Twenty-two years after its
      discovery, PACAP is now one of the most extensively studied of the neuropeptides.
      This review surveys the importance of PACAP and PACAP-like peptides in
      invertebrates, focusing mainly on the gastropod molluscs. The relevance of
      studies on lower vertebrates and invertebrates, which do not have a pituitary
      gland, is to contribute to the unraveling of fundamental effects of PACAP or
      PACAP-like peptides and to provide a comparative view.

PMID- 22630127
TI  - Insight into molecular and functional diversity of tachykinins and their
      receptors.
AB  - Tachykinins (TKs) and their structurally related peptides constitute the largest
      peptide superfamily in the animal kingdom. TKs have been shown to play various
      physiological roles not only as major brain/gut peptides but also as
      endocrine/paracrine hormones in chordates and exocrine factors in amphibians.
      Recent studies have also revealed that the biological roles of TKs as brain/gut
      peptides and endocrine/paracrine factors are essentially conserved in
      protochordates, and that alternative splicing mechanism in mammalian TK genes
      were established during the evolution of vertebrates. Protostomes possess two
      structurally and functionally different peptides; invertebrate TKs (inv-TKs)
      serve as toxin-like compounds secreted from the salivary gland of several
      organisms, whereas TK-related peptides (TKRPs) are functional counterparts for
      chordate TKs. Additionally, a TKRP-like sequence was detected in a diploblastic
      organism. The dramatic difference in structural organizations between TKRP
      precursors and chordate TK precursors clearly indicates the distinct evolutionary
      processes of TKs and TKRPs. Despite high sequence homology, TK receptors manifest
      selective affinity to their endogenous ligands, while TKRPs exhibit redundant
      activity at their receptors. Moreover, in addition to nociceptive, inflammatory,
      and contractile effects as brain/gut peptides, a number of studies have revealed
      novel biological effects of TKs on the hypothalamus and genital organs, revealing
      the biological roles of TKs as pivotal regulators of reproduction. These findings
      shed light on complicated evolutionary lineages of both structures and functions
      of the TK/TKRP superfamily and their receptors. In this review, we present basic
      and latest knowledge of the TK/TKRP superfamily with various points of view.

PMID- 22630129
TI  - First-line bevacizumab, cisplatin and vinorelbine plus maintenance bevacizumab in
      advanced non-squamous non-small cell lung cancer chemo-naive patients.
AB  - OBJECTIVE: The aim of this study was to evaluate efficacy and safety of first
      line treatment with bevacizumab, cisplatin and vinorelbine and bevacizumab
      maintenance in non-squamous, non-small cell lung cancer (NSCLC). RESEARCH DESIGN
      AND METHODS: Forty-nine patients with stage IIIB plus pleural effusion or stage
      IV NSCLC were included in a Phase II clinical trial. Treatment consisted of 3
      week cycles of bevacizumab (15 mg/kg on day 1), cisplatin (80 mg/m(2) on day 1)
      and vinorelbine (25 mg/m(2) on days 1 and 8). After 6 cycles, non-progressing
      patients received bevacizumab maintenance therapy. The primary end point was
      progression-free survival (PFS), calculated using the Kaplan-Meier method.
      RESULTS: Thirteen (29%) of 45 evaluable patients presented a partial response.
      PFS and overall survival were 6.0 months (95% confidence interval (CI) 4.5 - 7.5)
      and 14.7 months (95% CI 8.4 - 21), respectively. Fourteen patients (28%)
      experienced grade 3 - 4 neutropenia and 7 (14%) experienced febrile neutropenia
      during the combination treatment. During the maintenance phase, the most frequent
      grade 3 - 4 adverse event was hypertension. Neither grade 3 - 4 thrombocytopenia
      nor toxic death was observed. CONCLUSIONS: The studied regimen achieved a similar
      efficacy to other regimens containing platinum doublets. The data provide further
      evidence that bevacizumab may be used in combination with multiple standard
      platinum-based doublets in this setting.

PMID- 22630128
TI  - Function-driven discovery of neuropeptides with mass spectrometry-based tools.
AB  - A number of unique challenges are inherent to the study of neuropeptides (NPs),
      both in determining their molecular structure and their function. Traditional
      studies follow a model in which novel NPs are discovered and identified, then
      investigated for function. These studies frequently use biochemical techniques
      that can be imprecise and cumbersome. Mass spectrometry (MS)-based tools are
      becoming important not only in precisely determining the identity of a NP or
      quantifying a compound with a known sequence, but also in studies where identity
      and putative function can be determined simultaneously. Tools based on MS and
      tandem MS (MS/MS) have been developed, both with isotope labeling strategies and
      label-free methods, that allow accurate quantitation of NP changes associated
      with behavior or physiological manipulation, concurrent with identification of
      sequence. MS and MS/MS have also been implemented with sampling methods that
      incorporate temporal or spatial information while determining functional role of
      a NP, such as microdialysis (MD) and imaging mass spectrometry (IMS). These
      advances in MS and sampling techniques allow investigation of a particular
      biological phenomenon to guide studies aimed to identify and characterize NPs.
      Permitting function to drive identification of relevant compounds allows for a
      broader understanding of the molecular underpinnings of these events. The NPs
      thus identified can then be validated with more conventional techniques, and
      successive iterations of identification and function determination will provide
      rich information about these compounds. This function-driven discovery of NPs
      using MS-based techniques is an important new approach for their study.

PMID- 22630130
TI  - Impact of the core components of the phosphoenolpyruvate-carbohydrate
      phosphotransferase system, HPr and EI, on differential protein expression in
      Ralstonia eutropha H16.
AB  - In Ralstonia eutropha H16, seven genes encoding proteins being involved in the
      phosphoenolpyruvate-carbohydrate phosphotransferase system (PEP-PTS) were
      identified. In order to provide more insights into the poly(3-hydroxybutyrate)
      (PHB)-leaky phenotype of the HPr/EI deletion mutants H16DeltaptsH, H16DeltaptsI,
      and H16DeltaptsHI when grown on the non-PTS substrate gluconate, parallel
      fermentations for comparison of their growth behavior were performed. Samples
      from the exponential, the early stationary, and late stationary growth phases
      were investigated by microscopy, gas chromatography and (phospho-) proteome
      analysis. A total of 71 differentially expressed proteins were identified using
      2D-PAGE, Pro-Q Diamond and Coomassie staining, and MALDI-TOF analysis. Detected
      proteins were classified into five major functional groups: carbon metabolism,
      energy metabolism, amino acid metabolism, translation, and membrane
      transport/outer membrane proteins. Proteome analyses revealed enhanced expression
      of proteins involved in the Entner-Doudoroff pathway and in subsequent reactions
      in cells of strain H16 compared to the mutant H16DeltaptsHI. Furthermore,
      proteins involved in PHB accumulation showed increased abundance in the wild
      type. This expression pattern allowed us to identify proteins affecting carbon
      metabolism/PHB biosynthesis in strain H16 and translation/amino acid metabolism
      in strain H16DeltaptsHI, and to gain insight into the molecular response of R.
      eutropha to the deletion of HPr/EI.

PMID- 22630131
TI  - Sulfinyl-mediated stereoselective Overman rearrangements and Diels-Alder
      cycloadditions.
AB  - The Overman rearrangement of allylic sulfinyl trichloroacetimidates affords
      sulfinyl trichloroacetamides with high stereoselectivity and excellent yields.
      Bis-allylic substrates lead to amido 2-sulfinyl butadiene derivatives in
      excellent yields, with total chemo- and diastereoselectivity. The Diels-Alder
      cycloaddition of related dienes is controlled by the sulfoxide moiety.

PMID- 22630132
TI  - EEG, brain maturation, and the development of retinopathy of prematurity.
AB  - OBJECTIVES: The factors that influence the central nervous system (CNS)
      development can affect either the retina or the brain cortex. Immaturity of the
      brain cortex reflects immaturity of the retina and vice versa. The immature
      retina is more vulnerable than the mature retina, and is therefore more likely to
      develop retinopathy of prematurity (ROP). The aim of this study was to compare
      electroencephalographic brain maturity with ROP severity. METHODS: Twenty-one
      prematurely born infants were divided into two groups according to the severity
      of ROP. The first group included 12 infants with ROP stage 3 or more and the
      second group included nine infants with ROP stage 2 or less. We have proposed an
      index of CNS maturity (M) as a percentage of interburst interval elongation
      compared with the norm using video-electroencephalography (vEEG). RESULTS: The
      median M value was 1.07 (range = 0.43-4.44) for infants with severe ROP and -0.1
      (range = -1.0 to 1.45) for infants with mild or no ROP (p = 0.000948).
      CONCLUSIONS: The study revealed that CNS maturation delay expressed as M value
      was higher among infants with severe ROP than among infants with mild or no ROP.
      EEG examination in prematurely born infants may prove to be a useful tool for
      predicting ROP development.

PMID- 22630133
TI  - Structural changes imposed on whey proteins by UV irradiation in a continuous UV
      light reactor.
AB  - The objective of this study was to investigate the structural changes of whey
      proteins during exposure in a continuous-flow UV reactor. Varying UV irradiation
      dosages were obtained by controlling the flow rate and the mixing speed. Whey
      protein isolate (WPI) solutions at concentrations of 1% and 5% (w/v) were
      circulated at flow rates ranging from 30 to 800 mL.min(-1), and changes in
      physicochemical properties of the proteins were investigated. Intrinsic
      fluorescence spectra and surface hydrophobicity measurements suggested changes in
      the tertiary structure of the proteins with UV exposure. The UV treatment also
      increased the concentration of total and accessible thiol groups in 1% WPI
      solutions, while no change was measured in 5% WPI solutions. Size-exclusion
      chromatography demonstrated the formation of UV-induced aggregates and oxidation
      products (N-formylkynurenine and dityrosine) of aromatic amino acids.
      Furthermore, the UV-induced changes in protein conformation increased the
      susceptibility of whey proteins to pepsin hydrolysis.

PMID- 22630134
TI  - Study protocol: Transition from localized low back pain to chronic widespread
      pain in general practice: identification of risk factors, preventive factors and
      key elements for treatment--a cohort study.
AB  - BACKGROUND: Chronic localized pain syndromes, especially chronic low back pain
      (CLBP), are common reasons for consultation in general practice. In some cases
      chronic localized pain syndromes can appear in combination with chronic
      widespread pain (CWP). Numerous studies have shown a strong association between
      CWP and several physical and psychological factors. These studies are population
      based cross-sectional and do not allow for assessing chronology. There are very
      few prospective studies that explore the predictors for the onset of CWP, where
      the main focus is identifying risk factors for the CWP incidence. Until now there
      have been no studies focusing on preventive factors keeping patients from
      developing CWP. Our aim is to perform a cross sectional study on the epidemiology
      of CLBP and CWP in general practice and to look for distinctive features
      regarding resources like resilience, self-efficacy and coping strategies. A
      subsequent cohort study is designed to identify the risk and protective factors
      of pain generalization (development of CWP) in primary care for CLBP patients.
      METHODS/DESIGN: Fifty-nine general practitioners recruit consecutively, during a
      5 month period, all patients who are consulting their family doctor because of
      chronic low back pain (where the pain is lasted for 3 months). Patients are asked
      to fill out a questionnaire on pain anamnesis, pain-perception, co-morbidities,
      therapy course, medication, socio demographic data and psychosomatic symptoms. We
      assess resilience, coping resources, stress management and self-efficacy as
      potential protective factors for pain generalization. Furthermore, we raise risk
      factors for pain generalization like anxiety, depression, trauma and critical
      life events. During a twelve months follow up period a cohort of CLBP patients
      without CWP will be screened on a regular basis (3 monthly) for pain
      generalization (outcome: incident CWP). DISCUSSION: This cohort study will be the
      largest study which prospectively analyzes predictors for transition from CLBP to
      CWP in primary care setting. In contrast to the typically researched risk
      factors, which increase the probability of pain generalization, this study also
      focus intensively on protective factors, which decrease the probability of pain
      generalization. TRIAL REGISTRATION: German Clinical Trial Register DRKS00003123.

PMID- 22630135
TI  - Proteomic evaluation of sheep serum proteins.
AB  - BACKGROUND: The applications of proteomic strategies to ovine medicine remain
      limited. The definition of serum proteome may be a good tool to identify useful
      protein biomarkers for recognising sub-clinical conditions and overt disease in
      sheep. Findings from bovine species are often directly translated for use in
      ovine medicine. In order to characterize normal protein patterns and improve
      knowledge of molecular species-specific characteristics, we generated a two
      dimensional reference map of sheep serum. The possible application of this
      approach was tested by analysing serum protein patterns in ewes with mild broncho
      pulmonary disease, which is very common in sheep and in the peripartum period
      which is a stressful time, with a high incidence of infectious and parasitic
      diseases. RESULTS: This study generated the first reference 2-DE maps of sheep
      serum. Overall, 250 protein spots were analyzed, and 138 identified.Compared with
      healthy sheep, serum protein profiles of animals with rhino-tracheo-bronchitis
      showed a significant decrease in protein spots identified as transthyretin,
      apolipoprotein A1 and a significant increase in spots identified as haptoglobin,
      endopin 1b and alpha1B glycoprotein.In the peripartum period, haptoglobin, alpha
      1-acid glycoprotein, apolipoprotein A1 levels rose, while transthyretin content
      dropped. CONCLUSIONS: This study describes applications of proteomics in putative
      biomarker discovery for early diagnosis as well as for monitoring the
      physiological and metabolic situations critical for ovine welfare.

PMID- 22630136
TI  - Criterion validity of a functional cognitive task in patients with severe
      traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To verify criterion validity of measures from a functional
      cognitive task (FCT) carried out with patients with severe traumatic brain injury
      (sTBI) at 2-5 years post-injury. METHODS AND PROCEDURES: Forty-six patients with
      sTBI took part in a long-term outcome study where the FCT and the
      Neurobehavioural Rating Scale-Revised (NBRS-R) were administered and the FIMTM
      instrument was rated. The FCT is a telephone information gathering task for
      evaluating functional cognitive skills. RESULTS: Ten of 16 measures of the FCT
      were significantly correlated with similar or related concepts from the NBRS-R.
      The FIMTM cognitive score and the individual items of this score were
      significantly correlated with 13 of the FCT measures and with the percentage of
      amount of information gathered. Internal consistency was good for 13 of 16
      measures. Overall, patients generally had mild difficulty on the FCT concepts.
      CONCLUSION: The FCT can be used with patients with sTBI to evaluate certain
      aspects of functional cognition. It has good criterion validity and internal
      consistency, but additional research is required to further measure reliability
      and its applicability to other severity of TBI and to other phases of recovery.

PMID- 22630137
TI  - The genome of the polar eukaryotic microalga Coccomyxa subellipsoidea reveals
      traits of cold adaptation.
AB  - BACKGROUND: Little is known about the mechanisms of adaptation of life to the
      extreme environmental conditions encountered in polar regions. Here we present
      the genome sequence of a unicellular green alga from the division chlorophyta,
      Coccomyxa subellipsoidea C-169, which we will hereafter refer to as C-169. This
      is the first eukaryotic microorganism from a polar environment to have its genome
      sequenced. RESULTS: The 48.8 Mb genome contained in 20 chromosomes exhibits
      significant synteny conservation with the chromosomes of its relatives Chlorella
      variabilis and Chlamydomonas reinhardtii. The order of the genes is highly
      reshuffled within synteny blocks, suggesting that intra-chromosomal
      rearrangements were more prevalent than inter-chromosomal rearrangements.
      Remarkably, Zepp retrotransposons occur in clusters of nested elements with
      strictly one cluster per chromosome probably residing at the centromere. Several
      protein families overrepresented in C. subellipsoidae include proteins involved
      in lipid metabolism, transporters, cellulose synthases and short alcohol
      dehydrogenases. Conversely, C-169 lacks proteins that exist in all other
      sequenced chlorophytes, including components of the glycosyl phosphatidyl
      inositol anchoring system, pyruvate phosphate dikinase and the photosystem 1
      reaction center subunit N (PsaN). CONCLUSIONS: We suggest that some of these gene
      losses and gains could have contributed to adaptation to low temperatures.
      Comparison of these genomic features with the adaptive strategies of
      psychrophilic microbes suggests that prokaryotes and eukaryotes followed
      comparable evolutionary routes to adapt to cold environments.

PMID- 22630138
TI  - Colonoscopic enema as rescue for inadequate bowel preparation before colonoscopy:
      a prospective, observational study.
AB  - AIM: Colonoscopy may need to be rescheduled because of inadequate bowel
      preparation. We evaluated the effectiveness of colonoscopic enema as rescue for
      an inadequate 1-day bowel preparation before colonoscopy. METHOD: Patients
      referred for afternoon colonoscopy were prospectively enrolled in the study
      during a 1-year period. Patients took bowel preparation (polyethylene glycol)
      solution on the morning of the endoscopy. If during colonoscopy the bowel
      preparation was poor, an enema of polyethylene glycol solution (500 ml) was
      instilled into the colon at the level of the hepatic flexure via the biopsy
      channel of the colonoscope which was then removed. The patient was allowed to
      recover from the propofol sedation and used the bathroom to evacuate the enema.
      The colonoscope was then introduced and the examination continued. RESULTS: Of
      504 patients undergoing colonoscopy, 26 (4.9%) received an enema. The median age
      was 59 (29-79) years and 19 (73%) were female. A subsequent successful
      colonoscopy was achieved in 25/26 (96%). There were no complications. The mean
      time spent for the entire colonoscopy from the initial preparation to the end of
      the examination including the enema was 7.6+/- 1.1h (5.4 h preparation, 0.2h
      first colonoscopy+enema, 0.66h waiting in the lavatory, 0.33h second colonoscopy
      and 1 h for recovery). CONCLUSION: Colonoscopic enema was highly successful as
      rescue for patients with inadequate bowel preparation and avoided postponement of
      the procedure.

PMID- 22630139
TI  - Wound infection, dressings and pain, is there a relationship in the chronic
      wound?
AB  - The focus on quality of life issues in wound care has justly taken a far greater
      importance. With the acceptance that pain can be a major factor to the patient,
      and in particular, pain at dressing change comes the opportunity for avoidance
      and/or reduction strategies. Whilst pain has been associated with wound infection
      for millennia, it is only much more recently that this has received due attention
      from research and clinical practice. In this study, the nature of pain, changes
      in pain and pain associated with infection are the focal points. A Delphi
      approach, now a frequently used tool in wound care research, has been used to
      obtain expert opinion on these aspects of management.

PMID- 22630140
TI  - Unveiling the fungal mycobiota present throughout the cork stopper manufacturing
      process.
AB  - A particular fungal population is present in the main stages of the manufacturing
      process of cork discs. Its diversity was studied using both dependent (isolation)
      and independent culture methods (denaturing gel gradient electrophoresis and
      cloning of the ITS1-5.8S-ITS2 region). The mycobiota in the samples taken in the
      stages before and after the first boiling seems to be distinct from the
      population in the subsequent manufacturing stages. Most isolated fungi belong to
      the genera Penicillium, Eurotium and Cladosporium. The presence of uncultivable
      fungi, Ascomycota and endophytes in raw cork was confirmed by sequencing. The
      samples taken after the first boiling contained uncultivable fungi, but in a few
      samples some isolated fungi were also detected. The main taxa present in the
      following stages were Chrysonilia sitophila, Penicillium glabrum and Penicillium
      spp. All applied techniques had complementary outcomes. The main factors driving
      the shift in cork fungal colonization seem to be the high levels of humidity and
      temperature to which the slabs are subjected during the boiling process.

PMID- 22630141
TI  - Blood donor haemovigilance in Yaounde, Cameroon.
AB  - BACKGROUND: Blood availability is an issue of concern in countries of sub-Saharan
      Africa where both the demand and discard rates of blood are high. Although some
      degree of attention is paid when transfusion reactions occur in recipients, no
      information is available on donor reactions in this setting. OBJECTIVES: This
      study was carried out in order to obtain some data on adverse reactions (ARs) to
      blood donations. It would make it possible to monitor and improve the safety of
      the donation procedure, which constitutes a strategy towards increasing donor
      supply by encouraging first-time donors to return in the absence of any negative
      outcomes of donation. METHODS: A hospital blood bank-based descriptive and
      prospective study was carried out to document ARs among 1034 blood donors from
      September 2010 to January 2011. A pre-structured data collection tool was used to
      record the signs and symptoms observed. RESULTS: The ARs occurred at a rate of
      2.8%. The most frequent reaction was hypotension which constituted 26.62% of all
      ARs. Haematomas represented 18.42% while weakness and dizziness were each noted
      in 13.16% of donors. There was no severe vasovagal reaction. Associated factors
      to vasovagal reactions were first-time donor status (P = 0.004), female sex (P =
      0.01) and low body weight (P = 0.02). CONCLUSION: Our results suggest that blood
      donation is a relatively safe procedure in our context. The frequency is higher
      than studies from developed countries. The association of AR with first-time
      blood donation needs to be verified in a larger study. However, it could suggest
      another benefit of regular blood donation.

PMID- 22630142
TI  - Lack of association between parental ABO blood type and autism spectrum
      disorders.

PMID- 22630143
TI  - When and for whom do frequencies facilitate performance? On the role of numerical
      literacy.
AB  - The thesis that the mind is better prepared to process frequencies-as compared to
      other numerical formats-continues to be debated. A recent aspect of this issue is
      the role of numeracy (numerical literacy; one's ability to understand and work
      with numerical information) and specifically the argument that individual
      differences in numeracy interact with numerical formats. This interaction, either
      that frequencies improve performance only for those of low numeracy or that
      frequencies work only for those of high numeracy, would suggest that better
      performance using frequencies could be due to (nonevolutionary) numeracy effects.
      The three present studies revisited prior work with cumulative probability,
      Bayesian reasoning, and scenario risk assessments to study the effects of
      numeracy on frequency facilitation. Results from these experiments consistently
      failed to replicate previous findings of interactions; however, a more consistent
      finding emerged of a straightforward frequency effect. The lack of interactions
      and observations of frequency main effects lend support to the evolutionary
      explanation of the frequency effect. In addition, some possible statistical
      processes are proposed to explain the observation of interactions in past
      studies.

PMID- 22630144
TI  - Polyelectrolyte multilayered nanoparticles: using nanolayers for controlled and
      targeted systemic release.

PMID- 22630145
TI  - The potential clinical impact of quantum dots.

PMID- 22630147
TI  - Oral insulin: deja vu?

PMID- 22630148
TI  - Interview: An interview with Chad Mirkin: nanomedicine expert. Interviewed by
      Hannah Stanwix.
AB  - Chad Mirkin speaks to Hannah Stanwix, Assistant Commissioning Editor   Professor
      Chad Mirkin received his Bachelor of Science Degree in Chemistry from Dickinson
      College (PA, USA) in 1986. He holds a PhD in Chemistry from Pennsylvania State
      University (PA, USA) and was a Postdoctoral Fellow at the Massachusetts Institute
      of Technology (MA, USA). He subsequently moved to Northwestern University (IL,
      USA) as a Professor of Chemistry in 1991. In 2004, Professor Mirkin became
      Director of the International Institute for Nanotechnology and holds that post
      currently. He is also the George B Rathmann Professor of Chemistry, Professor of
      Chemical and Biological Engineering, Professor of Biomedical Engineering,
      Professor of Materials Science and Engineering and Professor of Medicine at
      Northwestern University. Professor Mirkin is a member of the National Academy of
      Engineering, the National Academy of Sciences, the Institute of Medicine, and the
      American Academy of Arts and Sciences. He is also currently a member of President
      Obama's Council of Advisors for Science and Technology. Professor Mirkin is best
      known for his work on spherical nucleic acid nanoparticle conjugates and the
      invention of Dip-Pen Nanolithography. He has received over 70 awards and
      accolades for his accomplishments. Currently, based on total citations, Professor
      Mirkin is one of the most cited chemists and nanomedicine researchers in the
      world. He has authored over 500 publications, as well as over 440 patents and
      applications worldwide.

PMID- 22630149
TI  - Gold nanoparticles as carriers for a synthetic Streptococcus pneumoniae type 14
      conjugate vaccine.
AB  - AIMS: Coupling of capsular polysaccharides of pathogens to immunogenic protein
      carriers (conjugate vaccines) improves carbohydrate immune response. Our idea is
      to explore gold nanoclusters as carriers to prepare fully synthetic carbohydrate
      vaccines. MATERIALS & METHODS: Gold glyconanoparticles bearing a synthetic
      tetrasaccharide epitope related to the Streptococcus pneumoniae type 14 capsular
      polysaccharide (Pn14PS), the T-helper ovalbumin 323-339 peptide (OVA(323-339)),
      and D-glucose were prepared by a one-pot method. Their immunogenicity was tested
      in mice. Cytokine levels after spleen cell stimulation with OVA(323-339) were
      analyzed using a luminex-multiplex cytokine assay. The capacity of the evoked
      antibodies to promote the uptake of S. pneumoniae type 14 by leukocytes was
      assessed. RESULTS & DISCUSSION: Glyconanoparticles containing 45% of
      tetrasaccharide and 5% OVA(323-339) triggered specific anti-Pn14PS IgG
      antibodies. Cytokine levels confirmed that glyconanoparticles led to T-helper
      cell activation. The anti-saccharide antibodies promoted the phagocytosis of type
      14 bacteria by human leukocytes, indicating the functionality of the antibodies.
      CONCLUSION: Gold nanoparticles have great potential as carriers for the
      development of a great diversity of fully synthetic carbohydrate-based vaccines.

PMID- 22630150
TI  - In vitro and in vivo characterization of temoporfin-loaded PEGylated PLGA
      nanoparticles for use in photodynamic therapy.
AB  - AIMS: In this study we evaluated temoporfin-loaded polyethylene glycol (PEG) Poly
      (D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) as a new formulation for
      potential use in cancer treatment. MATERIALS & METHODS: NPs were characterized
      for their photophysical properties, temoporfin release, cellular uptake and
      intracellular localization, and dark and photocytotoxicities of temoporfin by
      using A549, MCF10A neoT and U937 cell lines. In vivo imaging was performed on
      athymic nude-Foxn1 mice. RESULTS: Temoporfin was highly aggregated within the NPs
      and the release of temoporfin monomers was faster from PEGylated PLGA NPs than
      from non-PEGylated ones. PEGylation significantly reduced the cellular uptake of
      NPs by the differentiated promonocytic U937 cells, revealing the stealth
      properties of the delivery system. Dark cytotoxicity of temoporfin delivered by
      NPs was less than that of free temoporfin in standard solution (Foscan((r)),
      Biolitec AG [Jena, Germany]), whereas phototoxicity was not reduced. Temoporfin
      delivered to mice by PEGylated PLGA NPs exhibits therapeutically favorable tissue
      distribution. CONCLUSION: These encouraging results show promise in using
      PEGylated PLGA NPs for improving the delivery of photosensitizers for
      photodynamic therapy.

PMID- 22630151
TI  - Complete inhibition of extranodal dissemination of lymphoma by edelfosine-loaded
      lipid nanoparticles.
AB  - BACKGROUND: Lipid nanoparticles (LNs) made of synthetic lipids Compritol((r)) 888
      ATO and Precirol((r)) ATO 5 were developed with an average size of 110.4 +/- 2.1
      and 103.1 +/- 2.9 nm, and an encapsulation efficiency above 85% for both type of
      lipids. These LNs decrease the hemolytic toxicity of the drug by 90%. MATERIALS &
      METHODS: Pharmacokinetic and biodistribution profiles of the drug were studied
      after intravenous and oral administration of edelfosine-containing LNs. RESULTS:
      This provided an increase in relative oral bioavailability of 1500% after a
      single oral administration of drug-loaded LNs, maintaining edelfosine plasma
      levels over 7 days in contrast to a single oral administration of edelfosine
      solution, which presented a relative oral bioavailability of 10%. Moreover,
      edelfosine-loaded LNs showed a high accumulation of the drug in lymph nodes and
      resulted in slower tumor growth than the free drug in a murine lymphoma xenograft
      model, as well as potent extranodal dissemination inhibition.

PMID- 22630153
TI  - Nanoprobes for hybrid SPECT/MR molecular imaging.
AB  - Hybrid imaging techniques provide enhanced visualization of biological targets by
      synergistically combining multiple imaging modalities, thereby providing
      information on specific aspects of structure and function, which is difficult to
      obtain by a single imaging modality. Advances in the field of hybrid imaging have
      resulted in the recent approval of PET/magnetic resonance (MR) imaging by the US
      FDA for clinical use in the USA and Europe. Single-photon emission computed
      tomography (SPECT)/MR imaging is another evolving hybrid imaging modality with
      distinct advantages. Recently reported progress in the development of a SPECT/MR
      imaging hybrid scanner provides a cue towards the need for multimodal SPECT/MR
      imaging nanoprobes to take full advantage of a scanner's simultaneous imaging
      capability. In this review, we present some of the latest developments in the
      domain of SPECT/MR hybrid imaging, particularly focusing on multimodal
      nanoprobes.

PMID- 22630152
TI  - MRI of prostate stem cell antigen expression in prostate tumors.
AB  - BACKGROUND: The prostate stem cell antigen (PSCA) is broadly overexpressed on the
      surface of prostate cancer cells. MATERIALS & METHODS: Anti-human PSCA monoclonal
      antibody (mAb 7F5) was bound to Fe(3)O(4)/Au (GoldMag) nanoparticles to serve as
      a PSCA-specific molecular MRI probe (mAb 7F5@GoldMag) for in vivo detection of
      prostate cancer cells. First, the efficacy of the antibody immobilization for the
      binding was assessed. Next, PC-3 (human prostate cancer cell line with PSCA
      overexpression) tumor-bearing mice were injected with mAb 7F5@GoldMag for MRI
      measurements while using mouse anti-human IgG bound to the particles
      (IgG@GoldMag) to serve as a nonspecific control. MRI examinations were conducted
      before and after injection of these probes at 6, 12 and 24 h; T2-weighted signal
      intensity within the tumors was measured. RESULTS: Targeted binding of the mAb
      7F5@GoldMag probe to PC-3 tumors was verified with optical images and MRI;
      selective binding was not observed for the nonspecific IgG@GoldMag probe.
      CONCLUSION: MRI measurements suggest the promising efficacy of this new approach
      for targeted molecular imaging of prostate tumors.

PMID- 22630154
TI  - Emerging engineered magnetic nanoparticulate probes for targeted MRI of
      atherosclerotic plaque macrophages.
AB  - Inflammation is known to present at all stages of atherosclerotic lesion/plaque
      development, which often progresses silently for decades, before the occurrence
      of acute clinical events. Rupture of mature complex plaques with ongoing
      inflammation can lead to thrombosis, and many adverse acute clinical events such
      as stroke, myocardial infarction and/or sudden coronary death. Among new
      generation noninvasive imaging modalities, molecular MRI with target-specific
      novel nanoparticulate contrast agents has shown great promise for the
      visualization of atherosclerosis at the molecular and cellular level in both
      animals and humans. Considering the key role macrophages play in atherosclerotic
      inflammation from lesion initiation to plaque rupture, this article reviews the
      recently engineered magnetic nanoparticulate probes targeting macrophages, their
      phagocytic activities, surface receptors and molecular products such as
      neutrophil gelatinase-associated lipocalin. The usefulness of some of these
      probes as multimodal and drug monitoring agents is also reviewed along with the
      challenges and future perspectives of the present developments for clinical
      benefit.

PMID- 22630156
TI  - Tailoring layer-by-layer capsules for biomedical applications.
AB  - Polymeric capsules have attracted great interest as versatile carrier systems in
      the area of medicine and pharmaceutics. These capsules are made by stepwise layer
      by-layer adsorption of polymers onto a template core, which can be removed to
      produce hollow capsules. The cavity of these capsules can host various cargo
      molecules while the capsules' wall can be functionalized towards desired
      properties by embedding specific moieties into the multilayers. Tuning of the
      capsules' properties influences their interaction with cells and tissues and
      paves the way towards the development of stimuli-responsive capsules releasing
      their payload at a target site. In this review, we describe the generation of
      tailored layer-by-layer capsules and focus hereby on numerous potential
      applications of this multifunctional delivery platform in biomedical settings. We
      review the current status in the field and discuss the opportunities, as well as
      the hurdles, to be overcome to successfully transfer this technology to
      therapeutic and diagnostic applications.

PMID- 22630159
TI  - The Journal of Biomolecular Structure and Dynamics Establishes Web Site.

PMID- 22630155
TI  - Molecular plasmonics for biology and nanomedicine.
AB  - The optical excitation of surface plasmons in metal nanoparticles leads to
      nanoscale spatial confinement of electromagnetic fields. The confined
      electromagnetic fields can generate intense, localized thermal energy and large
      near-field optical forces. The interaction between these effects and nearby
      molecules has led to the emerging field known as molecular plasmonics. Recent
      advances in molecular plasmonics have enabled novel optical materials and devices
      with applications in biology and nanomedicine. In this article, we categorize
      three main types of interactions between molecules and surface plasmons: optical,
      thermal and mechanical. Within the scope of each type of interaction, we will
      review applications of molecular plasmonics in biology and nanomedicine. We
      include a wide range of applications that involve sensing, spectral analysis,
      imaging, delivery, manipulation and heating of molecules, biomolecules or cells
      using plasmonic effects. We also briefly describe the physical principles of
      molecular plasmonics and progress in the nanofabrication, surface
      functionalization and bioconjugation of metal nanoparticles.

PMID- 22630160
TI  - Cancer Watch Establishes Web Site.

PMID- 22630161
TI  - Malignant disease in the haemophilic population: moving towards a management
      consensus?
AB  - The Malignancy in Haemophilia Workshop Group convened a consensus working group
      of haematologists and oncologists to review topics related to malignancy in
      haemophilia. The treatment of malignant disease in this population is
      increasingly relevant as both outcome and lifespan continue to improve. Although
      adequate guidance exists for control of spontaneous bleeding episodes and of
      haemostasis in general surgery, information for management of haemostasis in
      patients with various malignancies is sparse. To date, no clinical guidelines
      exist for management of complex bleeding problems, diagnosis, therapy and follow
      up of malignancies in haemophilia. Furthermore, it remains unclear whether or not
      morbidity and mortality outcomes associated with malignancies are affected by
      haemophilia or by its treatment. Through presentation of five malignancies -
      prostate cancer, colorectal cancer, acute leukaemia, bladder cancer and
      hepatocellular carcinoma - important issues are highlighted, such as risk from
      bleeding as a symptom of malignancy; risks from invasive screenings and how these
      should be handled in haemophilic individuals; the implications of chemotherapy
      and treatment schedules, bone marrow suppression, radiotherapy, or surgery; and
      the likelihood of an interaction between treatment for haemophilia and malignancy
      outcomes. Ultimately, the aim is to establish consensus guidelines to direct and
      harmonize future treatment policy for malignant disease in the haemophilic
      population.

PMID- 22630162
TI  - Successful nanolitre real-time PCR detection of respiratory pathogens in clinical
      specimens.
AB  - We performed a proof-of-concept study to determine if human pathogens could be
      detected in clinical specimens using nanolitre-volume real-time PCR. Nanolitre
      PCR for Bordetella pertussis/B. parapertussis and respiratory syncytial virus
      (RSV) was performed on nasopharyngeal specimens and results compared with
      conventional methods. B. pertussis/B. parapertussis nanolitre PCR detection was
      100% sensitive (20/20; 95% CI, 84-100%) and 100% specific (26/26; 95% CI, 87
      100%). RSV nanolitre PCR was also 100% sensitive (21/21; 95% CI, 85-100%) and
      specific (25/25; 95%, CI 87-100%). Respiratory pathogens can be successfully
      detected in clinical specimens using nanolitre-volume PCR.

PMID- 22630163
TI  - The effects of oxcarbazepine and valproate therapies on growth in children with
      epilepsy.
AB  - AIM: This study aimed to evaluate the effects of monotherapy with valproate or
      oxcarbazepine on the linear growth of children with idiopathic epilepsy. METHODS:
      Antiepileptic treatment with valproate or oxcarbazepine was initiated in 76
      patients. These were evaluated at baseline and at 6 and 18 months after
      commencement of therapy to determine height standard deviations (height z
      scores). Serum ghrelin, insulin-like growth factor-1, and insulin-like growth
      factor-binding protein-3 levels were measured. RESULTS: In prepubertal patients
      receiving oxcarbazepine, height z-scores were elevated after 6 and 18 months of
      therapy (p = 0.008 and p = 0.001, respectively); in pubertal patients, a
      significant increase was noted at the 18th month of therapy (p = 0.004). In
      prepubertal patients receiving oxcarbazepine, serum standardized insulin-like
      growth factor-1 and insulin-like growth factor-binding protein-3 levels were
      significantly higher at the 18th month of therapy compared with baseline (p =
      0.005 and p = 0.004, respectively). In puber-tal patients receiving valproate,
      serum ghrelin levels were significantly decreased at the 18th month of therapy
      compared with baseline (p = 0.006). CONCLUSION: Exposure to oxcarbazepine
      stimulated linear growth in epileptic patients through mechanisms involving the
      release of insulin-like growth factor-1 and insulin-like growth factor-binding
      protein-3. In contrast, expo-sure to valproate did not affect linear growth, but
      did lead to a decrease in serum ghrelin levels.

PMID- 22630164
TI  - Features of Staphylococcus aureus colonization in patients with nummular eczema.

PMID- 22630165
TI  - Self-emulsifying bifendate pellets: preparation, characterization and oral
      bioavailability in rats.
AB  - In this study, a self-emulsifying pellet (SEP) was prepared in order to improve
      the bioavailability of bifendate (DDB). First, a liquid self-emulsifying drug
      delivery system (SEDDS) was formulated, and then further developed into the SEP
      by extrusion/spheronization technology using the reconstituted emulsion as the
      adhesive. The optimized liquid SEDDS consisted of Miglycol((r)) 840, a mixture of
      Cremorphor((r)) EL and Solutol HS((r)) 15 (1:2, w/w), and Transcutol HP as the
      oil phase, the surfactant and the co-surfactant at a weight ratio of 40:45:15
      (w/w/w), respectively. The SEP were prepared using a mixture of MCC, lactose, and
      mannitol (45:45:10, w/w/w) as solid adsorbents. The SEP with 40% (w/w) of the
      liquid SEDDS was round-shaped with a uniform size (800-1000 um). There was no
      difference in droplet size between the emulsions obtained from the liquid SEDDS
      or the SEP (169.8 +/- 6.3 nm and 163.7 +/- 3.8 nm). Compared with that of DDB
      pills (less than 20%), in vitro release of DDB from the SEP (over 80% within 60
      min) was significantly enhanced in 0.1N HCl, although slower than that of the
      liquid SEDDS (over 80% within 5 min). AUC of DDB of the SEP after oral
      administration in rats exhibited 2.36-fold greater than that of DDB pills and no
      significant difference compared with that of the liquid SEDDS. In conclusion, our
      studies illustrated that extrusion/spheronization technique could be a useful
      method to prepare this SEP and it could be a promising way for enhancing oral
      bioavailability of poorly water-soluble drugs.

PMID- 22630166
TI  - A cell-penetrating ratiometric nanoprobe for intracellular chloride.
AB  - NanoChlor, a nanoparticle-based fluorescent probe for chloride that is both
      ratiometric and capable of spontaneously penetrating neuronal cells at
      submillimolar concentrations, was designed and studied. NanoChlor is built on
      silica nanoparticles grafted with 6-methoxyquinolinium as the chloride-sensitive
      component and fluorescein as the reference dye. A Stern-Volmer constant of 50 M(
      1) was measured in Ringer's buffer at pH 7.2, and the response to chemically
      induced chloride currents was recorded in real time in hippocampal cells.

PMID- 22630167
TI  - Set shifting and central coherence as neurocognitive endophenotypes in eating
      disorders: a preliminary investigation in twins.
AB  - OBJECTIVES: Weak central coherence and poor set shifting are risk markers for
      eating disorders that are present post recovery and in first degree relatives.
      The aim of this study was to examine these traits in twins with eating disorders.
      METHODS: Neuropsychological tests were administered to 114 female twins (n = 53
      met lifetime DSM-IV eating disorder criteria, n = 19 non-eating disorder cotwins
      and n = 42 controls). Within pair correlations for monozygotic (MZ) and dizygotic
      (DZ) twins were calculated and generalised estimating equations (GEE) compared
      probands, with non-eating disorder cotwins and controls. RESULTS: The genetic
      basis was highest for the central coherence tasks (Rey-Osterrieth Complex Figure
      Task: MZ twins r = 0.44 [CI: 0.07-0.70, P = 0.01] and Group Embedded Figures
      Test: MZ twins r = 0.58 [CI: 0.26-0.79, P = 0.00]). Poor set shifting was related
      to obsessive compulsive symptoms in both individuals with eating disorders and
      their non-eating disorder cotwins (r = 0.2-0.5). CONCLUSION: Set shifting
      abilities and central coherence appear to be endophenotypes associated with
      eating disorders.

PMID- 22630168
TI  - Unexpected acidity enhancement triggered by AlH3 association to phosphines.
AB  - The complexes formed by the interaction between a series of phosphines R-PH(2) (R
      = H, CH(3), c-C(3)H(5), C(6)H(5)) and AlH(3) have been investigated through the
      use of high-level G4 ab initio calculations. These very stable complexes behave
      as much stronger acids than the isolated phosphines. This dramatic acidity
      enhancement, which can be as high as 174 kJ mol(-1), results from a much greater
      stabilization of the anionic deprotonated species with respect to the neutral
      one, upon AlH(3) association. This effect depends quantitatively on the nature of
      the substituent R and is smaller for R = C(6)H(5) because of the conjugation of
      the P lone pair with the aromatic system. More unexpectedly, however, the
      phosphine-alane complexes, RPH(2):AlH(3), are more acidic than the corresponding
      phosphine-borane RPH(2):BH(3) analogues. This unexpected result is due to the
      enhanced stability of the anionic deprotonated species for complexes involving
      AlH(3), because the delocalization of the newly created P lone pair with the P-Al
      bonding density is more favorable when the Lewis acid is aluminum trihydride than
      when it is borane.

PMID- 22630169
TI  - Use of human amelogenin in molecular encapsulation for the design of pH
      responsive microparticles.
AB  - BACKGROUND: Proteins can be used in drug delivery systems to improve
      pharmacological properties of an active substance. Differences in pH between
      tissues can be utilized in order to achieve a targeted drug release at a specific
      location or tissue, such as a tumor. The enamel matrix protein amelogenin has a
      pH dependent solubility profile and self-assemble to form aggregates at neutral
      pH. This could make amelogenin useful in the design of pH responsive drug
      delivery systems. RESULTS: In this study amelogenin was evaluated as a pH
      responsive component in drug delivery applications. This was achieved by testing
      the ability of amelogenin to entrap/release other proteins upon changes in pH,
      and by testing if amelogenin could confer pH responsiveness to an existing and
      versatile drug delivery system, such as gelatin microparticles. Amelogenin was
      able to encapsulate bovine serum albumin and insulin, whichwere used as model
      target proteins. The composite aggregates of amelogenin and target protein were
      formed at neutral pH and could be reversibly solubilized at weakly acidic pH.
      Gelatin microparticles prepared in the presence of amelogenin, showed a modulated
      structure in response to pH change, when studied by scanning electron microscopy,
      compared to particles without amelogenin. At neutral pH amelogenin induced
      formation of pores in the particle surface, which were not present at acidic pH,
      or in particles lacking amelogenin. CONCLUSIONS: The results from this study
      demonstrate that amelogenin can be a useful component in drug delivery systems in
      order to achieve a pH dependent response.

PMID- 22630170
TI  - Evaluation of expression and function of vascular endothelial growth factor
      receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and
      RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma.
AB  - BACKGROUND: Toceranib phosphate (Palladia) has a reported objective response rate
      of 25% in both canine apocrine gland anal sac adenocarcinoma (AGASACA) and
      thyroid carcinoma (TC), with stable disease occurring in an additional 50-60% of
      dogs. The basis for the observed responses to toceranib is not known. The purpose
      of this study was to evaluate AGASACA and TC samples for the expression and
      activation of VEGFR2, PDGFRalpha, PDGFRbeta, KIT and RET to assess whether
      dysregulation of these receptor tyrosine kinases (RTKs) may contribute to the
      biologic activity of toceranib. RESULTS: mRNA for VEGFR2, PDGFRalpha/beta, KIT
      and RET was detected in all AGASACA samples. mRNA for VEGFR2, PDGFRalpha/beta,
      and KIT was detected in all TC samples, while mRNA for RET was amplified in 10/15
      samples. No phosphorylation of VEGFR2, PDGFRalpha/beta, or KIT was observed on
      the arrays. However, phosphorylation of RET was detected in 54% of the primary
      AGASACA and 20% of TC. VEGFR2 was expressed in 19/24 primary and 6/10 metastatic
      AGASACA and 6/15 TC samples. KIT was present in 8/24 primary and 3/10 metastatic
      AGASACA and 9/15 TC samples. PDGFRalpha expression was noted in all tumor
      samples. In contrast PDGFRbeta expression was found in only a few tumor samples
      but was evident in the stroma of all tumor specimens. CONCLUSIONS: Known targets
      of toceranib are expressed in both AGASAC and TC. Given the observed expression
      of VEGFR and PDGFRalpha/beta and phosphorylation of RET, these RTKs merit
      investigation as to their roles in the biology of AGSACA and TC and their
      contribution to toceranib's activity.

PMID- 22630171
TI  - Gold nanoparticle-based immuno dual probes for targeting proteomics.
AB  - Immunoprecipitation combined with mass spectrometry (MS) is a promising technique
      for targeting proteomics in characterizing submicrograms of target protein and
      interacting proteins in living cells. This method, however, is limited by
      interference arising from nonspecific binding. We report a novel gold
      nanoparticle (AuNP)-based immuno probe approach for immunoprecipitation. By cross
      linking the antibody Fc domain to protein G covalently modified on AuNPs, the
      probe was fabricated and characterized to have 60 protein G and 30 immunoglobins
      per AuNP. We used human immunoglobin against the target and mouse immunoglobin
      with the same isotype (IgG) to fabricate the target and preclear probe,
      respectively, and termed it as the dual probe approach. Our results showed that
      the preclear probe (AuNP-IgG) and the target probe (AuNP-anti-ERalpha) share a
      similar panel of nonspecific binders but dramatic different specificity toward
      the target. Thus, using the dual probe method, we showed major nonspecific
      binders in the cell lysate could be largely removed without sacrificing the
      target protein. Compared to the conventional agarose gel-chromatography, the AuNP
      based probe exhibited less nonspecific interference and higher recovery yield for
      ERalpha. Moreover, the AuNP-based probe is more inert than the agarose gel under
      harsh conditions and does not induce dissociation of the cross-linked IgG that
      could interfere with target identification. Using AuNP-based dual probes, ERalpha
      was shown to be purified from MCF-7 cells with minimum nonspecific binding.
      Moreover, the identity and phosphorylation sites on the C-terminus of the
      purified ERalpha could be positively confirmed by MS using only 1 mg of cellular
      protein.

PMID- 22630328
TI  - Urinary heme oxygenase-1 in children with congenital hydronephrosis due to
      ureteropelvic junction obstruction.
AB  - CONTEXT: Heme oxygenase-1 (HO-1) is implicated to be correlated with renal
      function in oxidative stress. OBJECTIVE: To determine whether urinary (u) HO-1 is
      associated with the progression of congenital obstructive hydronephrosis (HN).
      METHODS: A total 50 children with HN (study group and control 1) and 30 healthy
      children were enrolled in this study. RESULTS: The uHO-1/cr levels increased
      significantly and negatively correlated with split renal function in study group
      before and during surgery. One month after surgery, it decreased significantly.
      CONCLUSION: Increased uHO-1 levels could be a potential biomarker for evaluating
      the progression of obstructive nephropathy.

PMID- 22630329
TI  - Performance validity and neuropsychological outcomes in litigants and disability
      claimants.
AB  - This study examined the relationship of performance validity and
      neuropsychological outcomes in a sample of individuals referred for independent
      neuropsychological examination in the context of reported traumatic brain injury
      (82% mild). Archival data were examined on 175 participants aged 20 to 65 who
      were administered at least two performance validity measures. Participants who
      passed all effort measures (Pass; n = 61) outperformed those who failed two or
      more (Fail; n = 70) on the majority of tests in the neuropsychological battery.
      The Fail group showed a higher percentage of impaired test scores than the Pass
      group with impairment defined at three levels (T scores < 40, 35, and 30). At the
      most conservative impairment cutoff (T < 30), 16% of the Pass group demonstrated
      impaired scores on more than three measures, while 79% of the Fail group showed
      impaired scores on more than three measures. The number of effort measures failed
      correlated highly with the overall test battery mean (r = -.73). On cognitive
      domain summary scores, effect sizes based on levels of effort (d = 1.12 to 1.86)
      were higher than those based on injury severity (d = 0.03 to 0.36).

PMID- 22630330
TI  - Novel method to reduce fishy aftertaste in wine and seafood pairing using alcohol
      treated yeast cells.
AB  - "Fishy aftertaste" is sometimes perceived in wine consumed with seafood. Iron in
      wine has been reported to be a key compound that produces fishy aftertaste.
      However, cost-effective methods to remove iron from wine have not been developed.
      Here, we describe a cost-effective and safe iron adsorbent consisting of alcohol
      treated yeast (ATY) cells based on the observation that nonviable cells adsorbed
      iron after completion of fermentation. Treatment of cells with more than 40%
      (v/v) ethanol killed them without compromising their ability to adsorb iron.
      Drying the ATY cells did not reduce iron adsorption. Use of ATY cells together
      with phytic acid had a synergistic effect on iron removal. We term this means of
      removing iron the "ATY-PA" method. Sensory analysis indicated that fishy
      aftertaste in wine-seafood pairings was not perceived if the wine had been
      pretreated with both ATY cells and phytic acid.

PMID- 22630331
TI  - Hyaluronic acid three-dimensional scaffold for surgical revision of retracting
      scars: a human experimental study.
AB  - An observational study was carried out at the Plastic and Reconstructive Surgery
      Unit of the University of Pavia - Salvatore Maugeri Research and Care Institute,
      Pavia, Italy, to assess the clinical and histological long-term outcomes of
      autologous skin grafting of fresh surgical wounds following previous repair with
      a hyaluronic acid three-dimensional scaffold (Hyalomatrix(r)). Eleven fresh
      wounds from surgical release of retracted scars were enrolled in this study. A
      stable skin-like tissue cover was observed in all of the treated wounds in an
      average 1 month's time; at the end of this study, after an average of 12 months'
      time, all of the reconstructed areas were pliable and stable, although an average
      retraction rate of 51.62% was showed. Histological observation and
      immunohistochemical analysis displayed integration of the graft within the
      surrounding tissues. A regenerated dermis with an extracellular matrix rich in
      type I collagen and elastic fibres and with reduced type III collagen rate was
      observed. The epidermis and dermoepidermal junction featured a normal appearance
      with well-structured dermal papillae, too. Although the histological features
      would suggest regeneration of a skin-like tissue, with a good dermis and no signs
      of scarring, the clinical problem of secondary contracture is still unsolved.

PMID- 22630333
TI  - The pregnancy-associated plasma protein A and insulin-like growth factor system
      in response to cigarette smoking.
AB  - OBJECTIVE: Maternal smoking during pregnancy is associated with a reduction in
      birth size but the mechanism by which this occurs still remains unclear. The
      purpose of this study was to evaluate the effect of tobacco smoking on
      concentrations of pregnancy-associated plasma protein A (PAPP-A), insulin-like
      growth factor I (IGF-I), II (IGF-II) and binding proteins BP-3 and BP-4 in
      pregnant women and correlations between these parameters. METHODS: Sixty healthy
      pregnant women were divided into smoking and tobacco-abstinent group according to
      results of serum cotinine concentration. The current smokers were defined as
      those who had smoked five or more cigarettes per day during pregnancy. RESULTS:
      The mean serum concentrations of PAPP-A, IGF-I and IGF-II were significantly
      lower in smoking than in non-smoking pregnant women (p < 0.01). The level of PAPP
      A correlated positively with the IGF-II concentration in both studied group (non
      smoking: r = 0.54; p < 0.001; smoking: r = 0.40; p < 0.05). In tobacco-abstinent
      group negative correlation between IGF-II and IGFBP-4 concentrations was found (r
      = -0.35; p < 0.05). CONCLUSION: Tobacco smoking during pregnancy decreases the
      pregnancy-associated plasma protein A and insulin growth factors I and II levels.
      The correlation between PAPP-A and IGF-II may suggest function of this protein as
      a protease and regulator in the IGF system.

PMID- 22630335
TI  - Accuracy, completeness and comprehensiveness of information on pressure ulcers
      recorded in the patient record.
AB  - AIM: To describe the accuracy, completeness and comprehensiveness of information
      on pressure ulcers documented in patient records. DESIGN AND SETTING: A cross
      sectional descriptive study performed in 29 wards at a university hospital in
      Iceland. The study included skin assessment of patients and retrospective audits
      of records of patients identified with pressure ulcers. PARTICIPANTS: A sample of
      219 patients was inspected for signs of pressure ulcers on 1 day in 2008. Records
      of patients identified with pressure ulcers were audited (n = 45)
      retrospectively. RESULTS: The prevalence of pressure ulcers was 21%. Information
      in patient records lacked accuracy, completeness and comprehensiveness. Only 60%
      of the identified pressure ulcers were documented in the patient records. The
      lack of accuracy was most prevalent for stage I pressure ulcers. CONCLUSIONS: The
      purpose of documentation to record, communicate and support the flow of
      information in the patient record was not met. The patient records lacked
      accuracy, completeness and comprehensiveness, which can jeopardise patient
      safety, continuity and quality of care. The information on pressure ulcers in
      patient records was found not to be a reliable source for the evaluation of
      quality in health care. To improve accuracy, completeness and comprehensiveness
      of data in the patient record, a systematic risk assessment for pressure ulcers
      and assessment and treatment of existing pressure ulcers based on evidence-based
      guidelines need to be implemented and recorded in clinical practice. Health
      information technology, including the electronic health record with decision
      support, has shown promising results to facilitate and improve documentation of
      pressure ulcers.

PMID- 22630332
TI  - Pharmacogene regulatory elements: from discovery to applications.
AB  - Regulatory elements play an important role in the variability of individual
      responses to drug treatment. This has been established through studies on three
      classes of elements that regulate RNA and protein abundance: promoters, enhancers
      and microRNAs. Each of these elements, and genetic variants within them, are
      being characterized at an exponential pace by next-generation sequencing (NGS)
      technologies. In this review, we outline examples of how each class of element
      affects drug response via regulation of drug targets, transporters and enzymes.
      We also discuss the impact of NGS technologies such as chromatin
      immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq), and the
      ramifications of new techniques such as high-throughput chromosome capture (Hi
      C), chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) and
      massively parallel reporter assays (MPRA). NGS approaches are generating data
      faster than they can be analyzed, and new methods will be required to prioritize
      laboratory results before they are ready for the clinic. However, there is no
      doubt that these approaches will bring about a systems-level understanding of the
      interplay between genetic variants and drug response. An understanding of the
      importance of regulatory variants in pharmacogenomics will facilitate the
      identification of responders versus non-responders, the prevention of adverse
      effects and the optimization of therapies for individual patients.

PMID- 22630336
TI  - A pilot study of urinary microRNA as a biomarker for urothelial cancer.
AB  - OBJECTIVE: MicroRNAs (miRNAs) are part of a class of small ribonucleic acid
      (RNAs). They are important regulatory molecules, involved in several cell
      processes, such as developmental timing, stem cell division and apoptosis.
      Dysregulated miRNAs have been identified in several human malignancies, including
      bladder cancer tissue samples, and may confer a "tumour signature" that can be
      exploited for diagnostic purposes. We report on a prospective pilot study
      investigating the diagnostic capability of miRNAs in the urine of patients with
      urothelial cancer. METHODS: Voided urine samples were collected from patients
      with urothelial carcinoma just prior to bladder tumour resection, as well as age
      matched healthy control patients. Pathology demonstrated both low- and high-grade
      cancer. Total RNA was isolated and quantitative reverse transcriptase-polymerase
      chain reaction was performed on the RNA extracts using primers for 4 miRNAs shown
      previously to be dysregulated in solid urothelial carcinomas with RNU6B as the
      endogenous control. Standard urine cytology was performed on all samples in a
      blinded fashion. RESULTS: Two miRNAs of interest were dysregulated in the urine
      from cancer patients with miR-125b showing an average 10.42-fold decrease (p <
      0.01) and miR-126 showing an average 2.70-fold increase (p = 0.30) in the cancer
      samples compared to the normal controls. The sensitivity and specificity of the
      cytology on the same urine samples were 50% and 80%, respectively. Using these 2
      miRNAs only, a decision-tree prediction model was generated for a validation
      cohort of patients yielding a specificity of 100% and a sensitivity of 80%.
      DISCUSSION: This preliminary study of candidate urinary miRNA in patients with
      low- and high-grade urothelial cancer demonstrated a significantly improved
      diagnostic accuracy over cytology. These results provide rationale for further
      studies on discovery and validation of candidate miRNAs in voided urine and may
      potentially lead to the development of a non-invasive and sensitive test for
      bladder cancer diagnosis and prognosis.

PMID- 22630337
TI  - Impact of body mass index on clinical outcomes associated with percutaneous
      nephrolithotomy.
AB  - INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is the preferred treatment for
      patients with large renal calculi or stones that have not responded to
      extracorporeal shock wave lithotripsy (ESWL). The objective of this study was to
      compare outcomes and complications of PCNL in patients of various body mass
      indices (BMI) to determine the safety of this procedure in patients with elevated
      BMI. METHODS: A retrospective chart review of 114 patients who underwent PCNL
      between 2006 and 2009 was performed. Patients were separated into 4 groups with
      respect to their BMI: (1) ideal body weight (BMI <25 kg/m(2)), (2) overweight
      (BMW 25-29 kg/m(2)), (3) obese (BMI 30-39 kg/m(2)) and (4) morbidly obese (BMI
      >=40 kg/m(2)). One-way ANOVA and univariate logistic regression analysis were
      used to assess the association between BMI (classified into 4 levels) and
      variables including age, sex, stone size, length of stay, incidence of
      complications and stone-free rates. RESULTS: The distribution of the 114 patients
      in each BMI category was: ideal body weight 39 (34%), overweight 24 (21%), obese
      41 (36%), morbidly obese 10 (9%). There was no difference in the composition of
      groups with respect to age, sex, pharmacologically treated comorbidities or stone
      size. Mean length of stay in days, intra- and postoperative complication rates
      were not statistically different. Stone-free rates showed no significant
      difference between groups: 90% ideal body weight; 87% overweight; 90% obese; 80%
      morbidly obese (p = 0.83). INTERPRETATION: Outcomes of PCNL were statistically
      independent of BMI. PCNL is a safe and efficacious treatment of stone disease in
      patients of all sizes.

PMID- 22630338
TI  - Photoselective vaporization of the prostate using GreenLight 120-W lithium
      triborate laser to treat symptomatic benign prostatic hyperplasia: A single
      centre prospective study.
AB  - OBJECTIVE: We evaluated the safety and efficacy of photoselective vaporization of
      the prostate (PVP) using GreenLight 120-W lithium triborate (LBO) laser to treat
      symptomatic small-to-medium sized benign prostatic hyperplasia (BPH). METHODS:
      This prospective non-controlled observational study included symptomatic BPH men
      >=50 years with international prostate symptom score (IPSS) >=14, prostate volume
      (PV) <=80 cc and maximum flow rate (Q-max) <=15 mL/s. PVP was performed using the
      GreenLight 120-W LBO laser machine. Patients were assessed at baseline and
      postoperatively at discharge, 2 weeks, and 3, 6 and 12 months. We measured
      changes in IPSS, PV, PSA, Q-max, post-void residual (PVR), hemoglobin (Hb), serum
      sodium (Na+) and reported complications. Statistical significance was p < 0.05.
      RESULTS: The study included 103 men with mean age of 67 (+/-standard deviation)+/
      9.7 years. Thirty patients were on indwelling urethral catheters for refractory
      urinary retention and 12 on ongoing anticoagulants. The mean baseline IPSS, PV,
      PSA, Q-max and PVR parameters significantly improved at follow-up (p < 0.001;
      each). Mean measurements at baseline versus at six months were: IPSS 25.6 +/- 4.2
      vs. 7.4+/-2.3; PV 44.6 +/- 9.2 vs. 21.6 +/- 6.3 cc (51.6% reduction); Q-max 5.8
      +/- 3.4 vs. 20.4 +/- 4.8 mL/s; PVR 110 +/- 40 vs. 35 +/- 9 cc. Mean baseline Hb
      and serum Na+ declined non-significantly (p > 0.05) at discharge and at 2 weeks.
      No patient needed a blood transfusion. Secondary procedures were needed in 2
      patients for urethral and bladder neck strictures. The re-treatment rate for
      residual adenoma was 0.97%. CONCLUSION: PVP using the GreenLight 120-W LBO laser
      to treat small-to-medium sized symptomatic BPH demonstrated significant
      improvements in efficacy parameters and high safety profile within 12 months of
      follow-up. The procedure entails good hemostasis with minimal blood loss even in
      patients receiving ongoing anticoagulants.

PMID- 22630339
TI  - The association between renal tumour scoring systems and ischemia time during
      open partial nephrectomy.
AB  - OBJECTIVE: To evaluate the association between renal tumour scoring systems and
      open partial nephrectomy ischemia time. METHODS: A historical cohort of open
      partial nephrectomy patients at The Ottawa Hospital between 2002 and 2009 was
      reviewed. Preoperative patient characteristics (age, gender, preoperative renal
      function, diabetes, hypertension, smoking history, heart disease) and ischemia
      time were abstracted from medical records. Preoperative computed tomography (CT)
      images were reviewed and tumours were characterized using three scoring systems:
      (1) R.E.N.A.L. nephrometry score (radius, exophytic/endophytic properties,
      nearness of tumour to the collecting system or sinus in millimetres,
      anterior/posterior, location relative to polar lines); (2) preoperative aspects
      and dimensions used for anatomic (PADUA) classification; and (3) Centrality index
      (C index). Patients without preoperative CT and patients treated with
      laparoscopic partial nephrectomy were excluded. RESULTS: During the study period,
      78 patients met the inclusion criteria. Median R.E.N.A.L. score was 7
      (interquartile range [IQR] 5-8), median PADUA score was 8 (IQR 7-10), and mean C
      index was 3.9 (standard deviation [SD] 2.1). Mean ischemia time was 23.4 (SD
      10.8) minutes. Five individual tumour characteristics (diameter, nearness to
      collecting system, anterior/posterior location, medial/lateral location, and
      collecting system involvement) were strongly associated with ischemia time (p <
      0.05). Increased R.E.N.A.L. score (1.5 minutes per unit 95%CI 0.08, 2.9, p =
      0.04) and PADUA score (2.0 minutes per unit 95%CI 0.5, 3.5, p = 0.009) were
      significantly associated with ischemia time. An increasing C index score was also
      associated with ischemia time (-1.1 minutes per unit 95%CI -2.2, 0.04, p = 0.06),
      but the association was not statistically significant. CONCLUSION: Renal tumour
      characteristics are associated with ischemia time. The proposed scoring systems
      are useful descriptors of surgical complexity and should be used when describing
      partial nephrectomy patients. Prospective evaluation and refinement of scoring
      systems are required to create an optimized model prior to widespread
      application.

PMID- 22630340
TI  - Long-term results of retroperitoneoscopic nephroureterectomy for upper urinary
      tract transitional cell carcinoma in China.
AB  - OBJECTIVE: We compared long-term clinical outcomes of upper urinary tract
      transitional cell carcinoma (TCC) patients treated by retroperitoneoscopic
      nephroureterectomy (RNU) or open radical nephroureterectomy (ONU). METHODS: Upper
      urinary tract TCC patients were treated with RNU (n = 86) or ONU (n = 72) and
      followed-up for more than three years. Demographic and clinical data, including
      preoperative indexes, intraoperative indexes and long-term clinical outcomes,
      were retrospectively compared to determine long-term efficacy of the two
      procedures. RESULTS: The RNU and ONU groups were statistically similar in age,
      gender, previous bladder cancer history, tumour location, pathologic tumour
      stage, pathologic node metastasis or tumour pathologic grade. The original
      surgery time required for both RNU and ONU was statistically similar, but RNU was
      associated with a significantly smaller volume of intraoperative estimated blood
      loss and shorter length of postoperative hospital stay. Follow-up (average: 42.4
      months, range: 3-57) revealed that the RNU 3-year recurrence-free survival rate
      was 62.8% and the 3-year cancer specific survival rate was 80.7%. In the ONU
      group, the 3-year recurrence-free survival and the three-year cancer-specific
      survival rates were 59.2% and 80.3%, respectively. Neither of the survival rates
      were statistically different between the two groups. T stage, grade, lymph node
      metastasis and bladder tumour history were risk factors for tumour recurrence;
      the operation mode and the bladder cuff incision mode had no correlation with the
      recurrence-free survival. CONCLUSION: The open surgery strategy and the
      retroperitoneoscopic nephroureterectomy strategy are equally effective for
      treating upper urinary tract TCC. However, the RNU procedure is less invasive,
      and requires a shorter duration of postoperative hospitalized care; thus, RNU is
      recommended as the preferred strategy.

PMID- 22630341
TI  - Patterns of functioning and predictive factors in children born moderately
      preterm or at term.
AB  - AIM: The aim of this study was to identify subgroups of children born moderately
      preterm (MPT) and term with distinctive levels and patterns of functioning, and
      the perinatal and demographic factors that predict subgroup membership. METHOD: A
      total of 378 children aged 7 years, 248 MPT (138 males, 110 females; gestational
      age 32-36 wks) and a comparison group of 130 children born at term (58 males, 72
      females; gestational age 38-41 wks), were selected from a community-based cohort
      study. Latent class analyses were performed on measures of intelligence, verbal
      memory, attention, executive functioning, and visuomotor and motor skills. chi(2)
      automatic interaction detection analyses were performed to detect associations
      between the subgroups and predictors. RESULTS: Four subgroups differing in levels
      of performance were identified, with parental education being the only
      statistically significant determinant of subgroup assignment (p < 0.01). The
      subgroup that performed the most poorly showed an irregular pattern of
      performance, with specific weakness in attentional skill and relative strength in
      intelligence and verbal memory. Parental education predicted classification
      probability in the preterm group (p = 0.04) but not in the term group (p = 0.15).
      INTERPRETATION: Our results show that the poorer performance of children born MPT
      reflects a higher proportion of children with below average performance rather
      than a subgroup with extremely poor performance. They indicate that MPT birth
      affects neurodevelopmental functioning at early school age only slightly, with
      effects being largest in such children with low parental education.

PMID- 22630342
TI  - Synthesis of trifluoromethyl-substituted cyclopropanes via sequential Kharasch
      dehalogenation reactions.
AB  - A two-step process for the synthesis of trifluoromethyl-substituted cyclopropanes
      is described. Halothane, an anesthetic agent, is added to olefins in a ruthenium
      catalyzed Kharasch reaction. The resulting 1,3-dihalides are converted into
      cyclopropanes by dehalogenation with magnesium. This procedure represents an
      alternative to metal-catalyzed cyclopropanations involving trifluoromethyl
      diazomethane.

PMID- 22630343
TI  - Acquired haemophilia in a patient with Castleman's disease: a case report.

PMID- 22630344
TI  - Detection of damaging nsSNPs on human caspase-cascades related to apoptotic
      signalling pathway.
AB  - In tumorigenesis, cancer genetics and the related mutations have been the main
      topic of study these days. Caspases have been found to be actively involved in
      the process of apoptosis. Malfunction of apoptosis is one of the causes for
      cancerous tumors and different caspase mutations are related to that process. It
      has been found that two groups of caspases involved in this process apoptosis
      which are initiator caspases and executioner caspases. SNPs have been extensively
      studied over the last decade, due to their association with a number of genetic
      diseases. Human SNPs have always been a source of information related to the
      complex changes associated with their origin. SNPs which can change the resulting
      amino acid i.e., nonsynonymous SNPs (nsSNPs) are of prime concern these days
      because of their direct relation with the disease or the respective individual.
      In this study our focus is not only to detect the nsSNPs available in the human
      caspase data but to further evaluate the potentially damaging nsSNPs. Using the
      computational approach we have been able to obtain almost seventy eight nsSNPs,
      among these few of the nsSNPs seem to have serious consequences, as they have
      been cross verified from a variety of SNP prediction tools. The functional as
      well as structural impact of the nsSNPs is determined and discussed. Our
      predicted nsSNPs on human caspases may be associated with cancer risk. 

PMID- 22630345
TI  - Stabilization of ferrochelatase via lysine residues on the carboxyl terminal
      extension.
AB  - There are accumulating evidences suggesting that ferrochelatase is involved in
      different cellular functions other than heme biosynthesis. The carboxyl-terminal
      extension of the enzyme may play a role associated with its stability and
      signaling process. Two transcript variants encoding different isoforms have been
      found for this ferrochelatase-coding gene. Variants encoding different isoforms
      have been found for this gene and were implicated in novel cellular activities
      including gene expression. Deficiency in ferrochelatase variants is believed to
      be associated with its stability. In this study, mutagenesis study of the lysine
      residues at 357, 360 and 365 was conducted. The relative change in activity by
      measurement of fluorescence intensity of the mutant enzyme revealed that K365L
      retained > 40% activity, while the mutant K365I retained 24% activity. Other
      mutants with K357S and K360Q showed little enzyme activity (< 4%). The change in
      the tryptophan fluorescence intensity after Guanidinium chloride-induced
      denaturation of the mutants indicated that the enzyme become unfolded under the
      assay condition. The K365L mutation suggests a structural role of tryptophan in
      the enzyme. The stability of the enzyme attributed to conservation of lysine
      residues in the C-terminal extension of the enzyme. The lysine and tryptophan
      residues serve as a structure determinant of ferrochelatase. 

PMID- 22630346
TI  - Molecular study of signaling-pathway genes in experimental rat thyroid carcinoma.
AB  - INTRODUCTION: A study was conducted on histological patterns and biomolecular
      changes in Goitrogen-induced experimental rat thyroid tumors. The link between
      the histological types observed and N-ras, B-raf, and PI3KCA gene mutations
      widely reported in human thyroid cancers was explored. MATERIAL AND METHODS: An
      analysis was done on paraffin-embedded tumor tissue sections from Wistar rats
      receiving 1% potassium perchlorate (KClO(4)) added to the ad libitum drinking
      water supply over an 18-month period. Three experimental subgroups were formed,
      each comprising 10 thyroids: subgroup I (control) consisted of thyroids from
      untreated controls; subgroups II and III (experimental) consisted of thyroids
      from KClO(4)-treated rats, displaying capsular, vascular, or both invasion but no
      metastasis (II), or distant metastasis (III). DNA was extracted from paraffin
      embedded tissues. To test for the genetic mutations most widely reported in human
      thyroid cancers, exon 1 of the N-ras gene, exons 9 and 20 of the PI3KCA gene, and
      exon 15 of the B-raf gene were amplified and sequenced. RESULTS: All tumors were
      of the follicular type. None of the 20 experimental rat thyroids displayed the
      expected gene mutations reported in humans. However, 90% of them contained four
      new B-raf gene mutations and all were silent and did not cause an amino acid
      substitution in the protein chain. CONCLUSIONS: Biomolecular analysis suggested
      that N-ras, PI3KCA, and B-raf gene mutations may not be involved in thyroid tumor
      formation using the experimental procedure applied in this study. But the four
      mutations in B-raf, though without functional repercussions, may be a specific
      marker for this tumor type.

PMID- 22630347
TI  - MicroRNA-21 expression is regulated by beta-catenin/STAT3 pathway and promotes
      glioma cell invasion by direct targeting RECK.
AB  - AIMS: MicroRNA-21 (miR-21) expression is increased in many types of human
      malignancy, including glioma. Recent studies report that miR-21 regulates cell
      invasion by targeting RECK, however, the underlying transcriptional regulation of
      miR-21 in glioma cells remains elusive. RESULTS: Here, we identify a positive
      correlation between miR-21 expression and pathological grade in glioma tissues.
      We demonstrate that beta-catenin pathway regulates miR-21 expression in human
      umbilical vein endothelial cell and glioma cells, and that this regulation is
      signal transducer and activator of transcription 3 (STAT3)-dependent. Further,
      chromatin immunoprecipitation and luciferase reporter analysis demonstrate that
      miR-21 is controlled by an upstream promoter containing a conserved STAT3 binding
      site. Notably, knockdown of miR-21-inhibited cell invasion by increasing RECK
      expression and decreased tumor growth in a xenograft model. CONCLUSION: These
      data provide compelling evidence that beta-catenin regulation of miR-21 via STAT3
      plays a role in glioma cell invasion and proliferation and indicate that STAT3 is
      a potential therapeutic target for glioma intervention.

PMID- 22630348
TI  - The evidence for the use of recombinant factor VIIa in massive bleeding: revision
      of the transfusion policy framework.
AB  - In 2006, the Canadian National Advisory Committee on Blood and Blood Products
      (NAC) developed a transfusion policy framework for the use of off-label
      recombinant factor VIIa (rFVIIa) in massive bleeding. Because the number of
      randomised controlled trials has doubled, the NAC undertook a review of the
      policy framework in 2011. On the basis of the review of 29 randomised controlled
      trials, there remains little evidence to support the routine use of rFVIIa in
      massive bleeding. Mortality benefits have not been demonstrated. Contrarily, an
      increase in arterial thromboembolic events has been observed with the use of off
      label rFVIIa. Given the absence of evidence of benefit and with evidence of the
      risk of harm, the NAC recommends that recombinant VIIa no longer be used for the
      off-label indications of prevention and treatment of bleeding in patients without
      haemophilia.

PMID- 22630349
TI  - Effects of direct spiking of silicone oil into a model pMDI formulation.
AB  - CONTEXT: Silicone oil is used as a valve lubricant in pressurized metered dose
      inhalers (pMDIs). Its possible impact on drug delivery, through such effects as
      particle aggregation, has recently been discussed. OBJECTIVE: To examine the
      effects of a range of directly spiked silicone oil amounts on pMDI performance.
      MATERIALS AND METHODS: pMDI canisters containing a corticosteroid medicinal
      compound, HFA134a and accurately measured amounts of silicone oil (0, 200, 400
      and 550 ug) were prepared. Samples were characterized for actuation weight,
      aerodynamic size (by Andersen cascade impaction, ACI), charge (by electrical low
      pressure impaction, ELPI) and product appearance by visual imaging. RESULTS AND
      DISCUSSION: Actuation weights were unaffected by silicone oil. A small increase
      in aerodynamic size was observed in the presence of silicone oil as a shift from
      stage 5 to impactor throat. No significant change in medicinal compound recovery
      was seen (t-tests, p > 0.05). Fine particle fraction as a percentage of dose
      delivered (FPF) was unchanged, as was particle size distribution derived from
      charge measurements, with the addition of silicone oil (t-tests, p > 0.05).
      Canister opening did not indicate container interaction but that sedimentation
      occurred in the presence of silicone oil. Decanted suspensions containing
      silicone oil were more transparent. Possible interactions inside and outside the
      pMDI canister are described. CONCLUSION: As demonstrated previously with an
      alternative experimental design the study showed that silicone oil has little
      effect on product performance, when added to a model pMDI formulation at levels
      that could potentially be observed as a leachable from the metering valve.

PMID- 22630350
TI  - The relationship between seven health practices and oral health status in
      community-dwelling elderly Thai.
AB  - OBJECTIVE: This study aims to analyse the relationship between seven health
      practices, oral health behaviors, and oral health status in community dwelling
      elderly Thai. MATERIALS AND METHODS: The subjects were 612 elderly people (mean
      age = 68.8 +/- 5.9 years). Questionnaires survey about sociodemographics, self
      reported seven health practices and oral health behaviors were conducted by
      trained interviewers. Oral examinations investigated the number of teeth present,
      decayed teeth, periodontal status and functional tooth units (FTUs). Oral malodor
      was assessed by Organoleptic Test, and unstimulated saliva was collected for 5
      min. RESULTS: Five health practices (smoking, drinking, physical activity,
      breakfast and weight maintenance) were significantly related with oral health
      behaviors. ancova analysis demonstrated the following significant associations:
      (i) smoking behavior with number of teeth present, number of FTUs, decayed teeth,
      periodontal disease, oral malodor and salivary flow rate, (ii) drinking alcohol
      behavior with number of teeth present, number of FTUs, periodontal disease, oral
      malodor and salivary flow rate, (iii) eating breakfast behavior with periodontal
      disease, oral malodor and salivary flow rate, (iv) eating between-meal snack with
      number of teeth present, number of FTUs, decayed teeth and periodontal disease,
      (v) maintaining weight with number of teeth present, number of FTUs, periodontal
      disease and oral malodor, (vi) sleeping with number of teeth present, number of
      FTUs, periodontal disease, oral malodor and salivary flow rate, (vii) physical
      activity with periodontal disease and salivary flow rate. CONCLUSION: Good health
      practices were related with good oral health behaviors. Moreover, general health
      practices were associated with the clinical oral health status such as number of
      teeth present, decayed teeth, FTUs, periodontal disease, oral malodor and
      salivary flow rate. The elderly with good general health practices were
      considered to have good oral health status. Improving general health habits are
      suggested to lead to better oral health for the elderly, and vice versa.

PMID- 22630353
TI  - A relation between different scales of electrophilicity: are the scales
      consistent along a chemical reaction?
AB  - In this paper, a relationship is established between three electrophilicity
      scales, namely, the electrophilicity index defined by Parr, Liu, and von
      Szentpaly; the electron affinity; and the energy of the lowest unoccupied
      molecular orbital (LUMO). Profiles of electrophilicity index and LUMO energies
      for different kinds of chemical reactions are compared to verify if they remain
      consistent during a whole chemical process. It appears that the electrophilicity
      index and the LUMO energies are linearly correlated in almost all the cases.
      Besides electrophilicity scales, profiles provide valuable information about the
      charge-transfer stage of a chemical process.

PMID- 22630354
TI  - Which factors decided general practitioners' choice of hospital on behalf of
      their patients in an area with free choice of public hospital? A questionnaire
      study.
AB  - BACKGROUND: Parts of New Public Management-reforms of the public sector depend on
      introduction of market-like mechanisms to manage the sector, like free choice of
      hospital. However, patients may delegate the choice of hospital to agents like
      general practitioners (GPs). We have investigated which factors Danish GPs
      reported as decisive for their choice of hospital on behalf of patients, and
      their utilisation of formal and informal data sources when they chose a hospital
      on behalf of patients. METHODS: Retrospective questionnaire study of all of the
      474 GPs practising in three counties which constituted a single uptake area.
      Patients were free to choose a hospital in another county in the country. The GPs
      were asked about responsibility for choice of the latest three patients referred
      by the GP to hospital; which of 16 factors influenced the choice of hospital;
      which of 15 sources of information about clinical quality at various
      hospitals/departments were considered relevant, and how often were six sources of
      information about waiting time utilised. RESULTS: Fifty-one percent (240 GPs)
      filled in and returned the questionnaire. One hundred and eighty-three GPs (76%)
      reported that they perceived that they chose the hospital on behalf of the latest
      referred patient. Short distance to hospital was the most common reason for
      choice of hospital.The most frequently used source of information about quality
      at hospital departments was anecdotal reports from patients referred previously,
      and the most important source of information about waiting time was the
      hospitals' letters of confirmation of referrals. CONCLUSIONS: In an area with
      free choice of public hospital most GPs perceived that they chose the hospital on
      behalf of patients. Short distance to hospital was the factor which most often
      decided the GPs' choice of hospital on behalf of patients. GPs attached little
      weight to official information on quality and service (waiting time) at hospitals
      or departments, focusing instead on informal sources like feedback from patients
      and colleagues and their experience with cooperation with the department or
      hospital.

PMID- 22630355
TI  - Adjunct methods for caries detection: a systematic review of literature.
AB  - OBJECTIVE: To assess the diagnostic accuracy of adjunct methods used to detect
      and quantify dental caries. STUDY DESIGN: A systematic literature search for
      relevant papers was conducted with pre-determined inclusion and exclusion
      criteria. Abstracts and full text articles were assessed independently by two
      reviewers. The study characteristics were compiled in tables and quality graded
      according to the QUADAS tool. The level of evidence for each diagnostic
      technology (fiber-optic methods, fluorescence methods, electrical methods) was
      based on studies of high or moderate quality according to the GRADE approach.
      RESULTS: Twenty-five reports fulfilled the inclusion criteria. One study was of
      high quality, 10 were graded as moderate, while the remaining 14 reports were of
      low quality. Electrical methods (ECM) and laser fluorescence (DIAGNOdent)
      displayed sensitivities and specificities around 70-80% regarding occlusal dentin
      lesions with a mean Youden's index of 0.52-0.54. The mean accuracy of laser
      fluorescence for detecting enamel and dentin lesions was 0.68 and 0.91,
      respectively. The heterogeneity of the published reports hampered the analysis.
      CONCLUSIONS: There was insufficient scientific evidence for diagnostic accuracy
      regarding fiber-optic methods and quantitative light-induced fluorescence (+OOO).
      The electrical methods and laser fluorescence could be useful adjuncts to visual
      tactile and radiographic examinations, especially on occlusal surfaces in
      permanent and primary molars, but evidence was graded as limited (++OO). No
      conclusions could be drawn regarding the cost-effectiveness of the methods. There
      is an obvious need to standardize study designs for in vitro and in vivo
      validation of the different methods.

PMID- 22630356
TI  - Orienting numbers in mental space: horizontal organization trumps vertical.
AB  - While research on the spatial representation of number has provided substantial
      evidence for a horizontally oriented mental number line, recent studies suggest
      vertical organization as well. Directly comparing the relative strength of
      horizontal and vertical organization, however, we found no evidence of
      spontaneous vertical orientation (upward or downward), and horizontal trumped
      vertical when pitted against each other (Experiment 1). Only when numbers were
      conceptualized as magnitudes (as opposed to nonmagnitude ordinal sequences) did
      reliable vertical organization emerge, with upward orientation preferred
      (Experiment 2). Altogether, these findings suggest that horizontal
      representations predominate, and that vertical representations, when elicited,
      may be relatively inflexible. Implications for spatial organization beyond
      number, and its ontogenetic basis, are discussed.

PMID- 22630357
TI  - Health, sport and nutritional information: tailoring your approach.
AB  - One of the intended legacies of the London 2012 Olympics is to increase the level
      of physical activity amongst the general population. Health information on the
      positive health benefits of sport and nutrition can assist in this goal and its
      positive benefit can been seen in communities within and beyond the United
      Kingdom, particularly within an educational context. In the United States, young
      people view their teachers as a valuable source of health information, and in
      Taiwan, teachers have been key collaborators in the development of a national
      Health e-Learning Network providing multimedia-learning modules for use in the
      classroom. However, classrooms are not the only source of health information and,
      with the reported inaccuracies in the translation of health information from
      academic papers to the popular press, school librarians have a role to play in
      facilitating students' ability to assess the quality of the health information
      they access, whatever the source.

PMID- 22630358
TI  - Implementation of Web 2.0 services in academic, medical and research libraries: a
      scoping review.
AB  - BACKGROUND: Academic, medical and research libraries frequently implement Web 2.0
      services for users. Several reports notwithstanding, characteristics and
      effectiveness of services are unclear. OBJECTIVES: To find out: the Web 2.0
      services implemented by medical, academic and research libraries; study designs,
      measures and types of data used in included articles to evaluate effectiveness;
      whether the identified body of literature is amenable to a systematic review of
      results. METHODS: Scoping review mapping the literature on the topic. Searches
      were performed in 19 databases. INCLUSION CRITERIA: research articles in English,
      Italian, German, French and Spanish (publication date >= 2006) about Web 2.0
      services for final users implemented by academic, medical and research libraries.
      Reviewers' agreement was measured by Cohen's kappa. From a data set of 6461
      articles, 255 (4%) were coded and analysed. RESULTS: Conferencing/chat/instant
      messaging, blogging, podcasts, social networking, wikis and aggregators were
      frequently examined. Services were mainly targeted at general academic users of
      English-speaking countries. CONCLUSIONS: Data prohibit a reliable estimate of the
      relative frequency of implemented Web 2.0 services. Case studies were the
      prevalent design. Most articles evaluated different outcomes using diverse
      assessment methodologies. A systematic review is recommended to assess the
      effectiveness of such services.

PMID- 22630359
TI  - A national survey of UK health libraries investigating the cost of interlibrary
      loan services and assessing the accessibility to key orthopaedic journals.
AB  - BACKGROUND:  NHS Library Services are utilised by NHS staff and junior trainees
      to locate scientific papers that provide them with the evidence base required for
      modern medical practice. The cost of accessing articles can be considerable
      particularly for junior trainees. OBJECTIVES:  This survey looks at variations in
      cost of journal article loans and investigates access to particular orthopaedic
      journals across the country. METHODS:  A national survey of UK Health Libraries
      was performed. Access to and costs of journals and interlibrary loan services
      were assessed. Availability of five wide-reaching orthopaedic journals was
      investigated. RESULTS:  Seven hundred and ten libraries were identified. One
      hundred and ten libraries completed the questionnaire (16.7%). Of these, 96.2%
      reported free access to scientific journals for users. 99.1% of libraries used
      interlibrary loan services with 38.2% passing costs on to the user at an average
      of L2.99 per article. 72.7% of libraries supported orthopaedic services. Journal
      of Bone and Joint Surgery (British) had greatest onsite availability.
      CONCLUSIONS:  The study demonstrates fluctuations in cost of access to
      interlibrary loan services and variation in access to important orthopaedic
      journals. It provides a reflection of current policy of charging for the
      acquisition of medical evidence by libraries in the UK.

PMID- 22630360
TI  - Dissemination of public health information: key tools utilised by the NECOBELAC
      network in Europe and Latin America.
AB  - BACKGROUND:  Open Access (OA) to scientific information is an important step
      forward in communication patterns, yet we still need to reinforce OA principles
      to promote a cultural change of traditional publishing practices. The advantages
      of free access to scientific information are even more evident in public health
      where knowledge is directly associated with human wellbeing. OBJECTIVES:  An OA
      'consolidation' initiative in public health is presented to show how the
      involvement of people and institutions is fundamental to create awareness on OA
      and promote a cultural change. This initiative is developed within the project
      NEtwork of COllaboration Between Europe and Latin American Caribbean countries
      (NECOBELAC), financed by the European Commission. METHODS:  Three actions are
      envisaged: Capacity building through a flexible and sustainable training
      programme on scientific writing and OA publishing; creation of training tools
      based on semantic web technologies; development of a network of supporting
      institutions. RESULTS:  In 2010-2011, 23 training initiatives were performed
      involving 856 participants from 15 countries; topic maps on scientific
      publication and OA were produced; 195 institutions are included in the network.
      CONCLUSIONS:  Cultural change in scientific dissemination practices is a long
      process requiring a flexible approach and strong commitment by all stakeholders.

PMID- 22630361
TI  - Human information behaviour and physiological measurements as a basis to tailor
      health information. An explorative study in a physical activity intervention
      among prediabetic individuals in Northern Finland.
AB  - OBJECTIVE:  To explore through an interdisciplinary approach the potential to
      tailor health information on the basis of human information behaviour (HIB) on
      par with the results of basic physiological measurements of individuals' health.
      METHODS:  The data were collected at the baseline of a physical activity and
      diabetes prevention intervention with 72 prediabetic participants, conducted in
      Oulu, Finland, by the University of Oulu and Oulu Deaconess Institute in 2010.
      Body mass index (BMI), fitness classifications and glucose values were obtained
      from all prediabetic participants. The interest in, the search for and the use of
      information on nutrition, physical activity and diabetes were examined through a
      self-report questionnaire with a response rate of 95.8%. The data were analysed
      with the SPSS statistics 18 software. RESULTS AND CONCLUSIONS:  The study shows
      that information behaviour of prediabetic individuals differs according to their
      BMI and fitness level. Poor physical fitness classifications and high BMI values
      were associated with an increased desire to receive tailored information on
      nutrition and physical activity frequently. These results add knowledge on the
      types and preferred frequencies of tailored information. Because of the small
      sample size, the results should be validated further.

PMID- 22630362
TI  - The performance of adverse effects search filters in MEDLINE and EMBASE.
AB  - BACKGROUND:  Search filters can potentially improve the efficiency of searches
      involving electronic databases such as medline and embase. Although search
      filters have been developed for identifying records that contain adverse effects
      data, little is known about the sensitivity of such filters. OBJECTIVES:  This
      study measured the sensitivity of using available adverse effects filters to
      retrieve papers with adverse effects data. METHODS:   A total of 233 included
      studies from 26 systematic reviews of adverse effects were used for analysis.
      Search filters from medline and embase were tested for their sensitivity in
      retrieving the records included in these reviews. In addition, the sensitivity of
      each individual search term used in at least one search filter was measured.
      RESULTS:  Subheadings proved the most useful search terms in both medline and
      embase. No indexing terms in medline achieved over 12% sensitivity. The
      sensitivity of published search filters varied in medline from 3% to 93% and in
      embase from 57% to 97%. Whether this level of sensitivity is acceptable will be
      dependent on the purpose of the search. CONCLUSIONS:  Although no adverse effects
      search filter captured all the relevant records, high sensitivity could be
      achieved. Search filters may therefore be useful in retrieving adverse effects
      data.

PMID- 22630363
TI  - Health education for Somali Bantu refugees via home visits.
AB  - BACKGROUND:  Somali Bantu refugees, with unique health information needs, created
      challenges for health and social service providers. OBJECTIVES:  A service
      innovation was developed (i) to raise awareness, especially among local health
      and social service providers, about the Bantu refugees' presence in the
      community, their culture, and their information needs and (ii) to deliver needed
      health information, emphasizing child health, to the Bantu mothers in their
      homes. METHODS:  The project consisted of: (i) a community conference targeting
      local health and social service providers, describing the refugees' presence in
      the community, their culture, and information needs. (ii) Focus groups conducted
      with members of the Bantu population elicited additional information needs. (iii)
      Curriculum was developed based on identified needs, and (iv) the curriculum was
      delivered to the refugees in their homes. A clinical informationist and MP3
      technology enhanced the project. FINDINGS:  Conference attendees' evaluation
      responses indicated improved understanding of Bantu culture. Focus groups'
      identification of health information needs provided a framework for the health
      education curriculum. A project website made educational materials available to
      other healthcare providers. CONCLUSIONS:  The project raised awareness of the
      Bantus' presence, culture, and information needs. Identification of other unmet
      needs demonstrated that additional support for refugees is required.

PMID- 22630364
TI  - Implementing RFID in a hospital library: a scoping study.
AB  - This article discusses a scoping study on implementing radio frequency
      identification device (RFID) in a hospital library context, conducted by Joseph
      Norwood for his MA dissertation at the University of Brighton. The study was
      carried out during the summer of 2011 to support possible RFID implementation at
      the Brighton and Sussex University Hospitals (BSUH) Trust, and the library staff
      were able to use the findings to good effect to create a business plan. This
      article also acts as the template for the new Dissertations into Practice
      feature, which was introduced in the March issue (Marshall, A. Health Information
      and Libraries Journal 2012, 29, 72). The dissertation highlighted here is very
      practical in nature and had immediate and quantifiable benefits for the Trust
      library. Future feature articles are likely to reflect the range of health
      related dissertation topics which students choose and will include studies on
      user information behaviour, information services related to mental health and
      well-being, as well as the impact of technology on health-related library or
      information services.AM.

PMID- 22630365
TI  - International trends in health science librarianship: Part 2--Northern Europe.
AB  - This is the third in a series of articles exploring international trends in
      health science librarianship in the first decade of the 21st century. The invited
      authors were asked to reflect on developments in their country--viz. Austria,
      Belgium, France and the Netherlands. Future issues will track trends in the
      Nordic countries, Southern Europe and Latin America. JM.

PMID- 22630366
TI  - Know your RO from your AE? Learning styles in practice.
AB  - In this article, Kolb's cycle of learning is put forward as a useful theory to
      consult when planning information literacy or other teaching sessions. The
      learning cycle is contextualised and Kolb's and other theories are briefly
      explored. The author then considers how learning style theories can be utilised
      when planning teaching and learning activities. The use of planning tools is
      advocated and ideas for sessions are suggested. HS.

PMID- 22630367
TI  - Effects of severity of post-flowering leaf removal on berry growth and
      composition of three red Vitis vinifera L. cultivars grown under semiarid
      conditions.
AB  - The effects of the severity of post-flowering leaf removal on the growth and
      phenolic composition of berry skin and seeds were studied in three Vitis vinifera
      L. genotypes over two consecutive seasons, 2007 and 2008. The study was conducted
      in a commercial vertical shoot positioned (VSP)-trained nonirrigated vineyard of
      northern Greece, planted with cultivars Merlot, Cabernet Sauvignon, and
      Sangiovese. Three different severities of leaf removal in the fruit zone were
      applied manually at berry set: nondefoliated (ND), removal of the lateral shoots
      of the first six basal nodes (LR), and full removal of the total leaf area (main
      leaves and lateral shoots) of the first six basal nodes (FR). Grape samples were
      obtained at commercial harvest. Leaf removal decreased yield per vine and cluster
      weight in Merlot and Sangiovese. Cluster compactness was reduced with the
      severity of defoliation only in Merlot, due to a decrease in berry number per
      cluster; berry fresh weight was unaffected in both cultivars. On the contrary, in
      Cabernet Sauvignon, yield was unaffected but berry size was restrained by leaf
      removal. Skin and seed mass followed variations in berry mass (except for seed
      mass in Sangiovese). Fruit zone leaf removal did not affect must soluble solids
      and increased titratable acidity only in Merlot. Defoliation increased skin
      anthocyanins in Merlot and Cabernet Sauvignon in the order FR > LR > ND but
      significantly reduced seed flavan-3-ols mainly as a result of the reduction in
      catechin and epicatechin amount. For these varieties, FR had lower seed flavan-3
      ols than ND in both varieties, whereas LR had intermediate values. However, in
      Sangiovese, the highest seed phenolic content was recorded in LR. The results
      showed that post-flowering leaf removal improved the overall berry composition in
      Merlot and Cabernet Sauvignon but had limited effect in Sangiovese. 

PMID- 22630368
TI  - Insignificant role of the N-terminal cobalt-binding site of albumin in the
      assessment of acute coronary syndrome: discrepancy between the albumin cobalt
      binding assay and N-terminal-targeted immunoassay.
AB  - The aim of this study was to evaluate whether the N-terminus of human serum
      albumin (HSA) has a role in the cobalt binding detected using albumin cobalt
      binding (ACB) assay. We compared the results obtained using an enzyme-linked
      immunosorbent assay (ELISA) for N-terminal-modified HSA with those of a
      conventional ACB assay in two groups: acute coronary syndrome (n = 43) and non
      ischemic chest pain (n = 39). ACB and cardiac troponin-I levels were higher in
      the acute coronary syndrome group. No significant correlation between ACB assay
      and ELISA results was observed in either of the two patient groups. In acute
      chest pain patients, the N-terminal site of HSA has a negligible or limited role
      in cobalt binding in the ACB assay.

PMID- 22630562
TI  - Acute mediastinal bleeding during vacuum-assisted closure.
AB  - Vacuum-assisted closure is commonly used to treat post-sternotomy mediastinitis.
      Several studies show improved outcome using vacuum-assisted therapy; however,
      risks using negative pressure should not be underestimated. We describe two cases
      of acute mediastinal bleeding during vacuum treatment for post-sternotomy
      mediastinitis and discuss preventative measurements.

PMID- 22630369
TI  - Risk stratification by residual enzyme activity after newborn screening for
      medium-chain acyl-CoA dehyrogenase deficiency: data from a cohort study.
AB  - BACKGROUND: Since the introduction of medium-chain acyl coenzyme A dehydrogenase
      (MCAD) deficiency in population newborn bloodspot screening (NBS) programs,
      subjects have been identified with variant ACADM (gene encoding MCAD enzyme)
      genotypes that have never been identified in clinically ascertained patients. It
      could be hypothesised that residual MCAD enzyme activity can contribute in risk
      stratification of subjects with variant ACADM genotypes. METHODS: We performed a
      retrospective cohort study of all patients identified upon population NBS for
      MCAD deficiency in the Netherlands between 2007-2010. Clinical, molecular, and
      enzymatic data were integrated. RESULTS: Eighty-four patients from 76 families
      were identified. Twenty-two percent of the subjects had a variant ACADM genotype.
      In patients with classical ACADM genotypes, residual MCAD enzyme activity was
      significantly lower (median 0%, range 0-8%) when compared to subjects with
      variant ACADM genotypes (range 0-63%; 4 cases with 0%, remainder 20-63%).
      Patients with (fatal) neonatal presentations before diagnosis displayed residual
      MCAD enzyme activities <1%. After diagnosis and initiation of treatment, residual
      MCAD enzyme activities <10% were associated with an increased risk of
      hypoglycaemia and carnitine supplementation. The prevalence of MCAD deficiency
      upon screening was 1/8,750 (95% CI 1/7,210-1/11,130). CONCLUSIONS: Determination
      of residual MCAD enzyme activity improves our understanding of variant ACADM
      genotypes and may contribute to risk stratification. Subjects with variant ACADM
      genotypes and residual MCAD enzyme activities <10% should be considered to have
      the same risks as patients with classical ACADM genotypes. Parental instructions
      and an emergency regimen will remain principles of the treatment in any type of
      MCAD deficiency, as the effect of intercurrent illness on residual MCAD enzyme
      activity remains uncertain. There are, however, arguments in favour of abandoning
      the general advice to avoid prolonged fasting in subjects with variant ACADM
      genotypes and >10% residual MCAD enzyme activity.

PMID- 22630564
TI  - Improvement of intra-epidermal nerve fibre density in hypothyroidism after L
      thyroxine therapy.

PMID- 22630563
TI  - Influence of the bilayer composition on the binding and membrane disrupting
      effect of Polybia-MP1, an antimicrobial mastoparan peptide with leukemic T
      lymphocyte cell selectivity.
AB  - This study shows that MP-1, a peptide from the venom of the Polybia paulista
      wasp, is more toxic to human leukemic T-lymphocytes than to human primary
      lymphocytes. By using model membranes and electrophysiology measurements to
      investigate the molecular mechanisms underlying this selective action, the
      porelike activity of MP-1 was identified with several bilayer compositions. The
      highest average conductance was found in bilayers formed by phosphatidylcholine
      or a mixture of phosphatidylcholine and phosphatidylserine (70:30). The presence
      of cholesterol or cardiolipin substantially decreases the MP-1 pore activity,
      suggesting that the membrane fluidity influences the mechanism of selective
      toxicity. The determination of partition coefficients from the anisotropy of Trp
      indicated higher coefficients for the anionic bilayers. The partition
      coefficients were found to be 1 order of magnitude smaller when the bilayers
      contain cholesterol or a mixture of cholesterol and sphingomyelin. The blue shift
      fluorescence, anisotropy values, and Stern-Volmer constants are indications of a
      deeper penetration of MP-1 into anionic bilayers than into zwitterionic bilayers.
      Our results indicate that MP-1 prefers to target leukemic cell membranes, and its
      toxicity is probably related to the induction of necrosis and not to DNA
      fragmentation. This mode of action can be interpreted considering a number of
      bilayer properties like fluidity, lipid charge, and domain formation. Cholesterol
      containing bilayers are less fluid and less charged and have a tendency to form
      domains. In comparison to healthy cells, leukemic T-lymphocyte membranes are
      deprived of this lipid, resulting in decreased peptide binding and lower
      conductance. We showed that the higher content of anionic lipids increases the
      level of binding of the peptide to bilayers. Additionally, the absence of
      cholesterol resulted in enhanced pore activity. These findings may drive the
      selective toxicity of MP-1 to Jurkat cells.

PMID- 22630565
TI  - Preterm birth and developmental problems in the preschool age. Part I: minor
      motor problems.
AB  - Nearly half of very preterm (VP) and extremely preterm (EP) infants suffers from
      minor disabilities. The paper overviews the literature dealing with motor
      problems other than cerebral palsy (CP) during infancy and preschool age. The
      term "minor motor problems" indicates a wide spectrum of motor disorders other
      than CP; "minor" does not mean "minimal", as a relevant proportion of the preterm
      infants will develop academic and behavioural problems at school age. Early onset
      disorders consist of abnormal general movements (GMs), transient dystonia and
      postural instability; these conditions usually fade during the first months. They
      were underestimated in the past; recently, qualitative assessment of GMs using
      Prechtl's method has become a major item of the neurological examination. Late
      onset disorders include developmental coordination disorder (DCD) and/or minor
      neurological dysfunction (MND): both terms cover partly overlapping problems.
      Simple MND (MND-1) and complex MND (MND-2) can be identified and MND-2 gives a
      higher risk for learning and behavioural disorders. A relationship between the
      quality of GMs and MND in childhood has been recently described. The Touwen
      infant neurological examination (TINE) can reliably detect neurological signs of
      MND even in infancy. However, the prognostic value of these disorders requires
      further investigations.

PMID- 22630566
TI  - Recent patenting activities in the discovery and development of vasopressin V2
      receptor agonists.
AB  - INTRODUCTION: Vasopressin V(2) agonists are well known as effective therapies in
      the treatment of central diabetes insipidus and nocturnal enuresis. Furthermore,
      given their mode of action, these particular agonists have more recently been
      considered, in both the pharmaceutical industry and in academia, as viable
      therapies for urological conditions such as nocturia. AREAS COVERED: For the past
      10 years, significant progress has been made in the discovery and development of
      vasopressin V(2) agonists. This article provides the reader with information on
      the recent progress in the discovery and development of these compounds based on
      patents published from 2002 onward. Specifically, the article looks at the
      discovery of new non-peptide agonists as well as well as novel formulations of
      the vasopressin V(2) agonist desmopressin. EXPERT OPINION: The V(2) receptor is
      currently one of the hottest therapeutic targets investigated for the treatment
      of urinary disorders such as nocturia and central diabetes. Over the past 10
      years, significant progress has been made in the discovery and development of
      vasopressin V(2) receptor agonists, for the treatment of these disorders. The
      author anticipates that these agonists will be launched to market in the not-too
      distant future.

PMID- 22630567
TI  - Medical radiation exposure in children with bleeding disorders: an institutional
      experience.
AB  - Patients with bleeding disorders may be exposed to ionizing radiation during
      medical care. We hypothesized that children with severe haemophilia may have
      higher radiation exposure than those with mild bleeding disorders (MBDs). To
      compare medical radiation exposure rates between children with severe haemophilia
      and MBDs. Charts of 35 pediatric patients with severe haemophilia were randomly
      selected from a database of active male patients followed in our bleeding
      disorders clinic from 2000 to 2010. Case patients were age and sex matched with
      two control patients with MBDs [Type 1 von Willebrand disease (VWD) or mild
      platelet function defect (PFD)]. By retrospective review, data on radiation
      exposure in millisieverts (mSv) was collected from radiological studies performed
      within Emory/CHOA. The rates of exposure between cohorts were compared using the
      Mann-Whitney Test. Case patients had a mean of 11.3 (median 8, IQR = 29)
      radiographic studies compared with 1.8 (median 1, IQR = 11) for controls (P <
      0.001). The mean effective dose of radiation per patient per year of study was
      two mSv for case patients (median 0.4, IQR = 3) and 0.4 mSv for control patients
      (median 0.01, IQR = 0.3) (P < 0.001). Overall, 1.4% of controls and 31.4% of
      cases accumulated high to very high levels of exposure ( > 20 mSv). Case patients
      with severe hemophilia accumulated significantly more medical radiation exposure
      than controls. While the use of ionizing radiation is often necessary for
      management of these patients, avoidance of unnecessary exposure along with
      exploration of alternative imaging techniques and low dose protocols should be
      considered whenever possible.

PMID- 22630568
TI  - Diagnosis and control measures of the 2010 outbreak of foot-and-mouth disease A
      type in the Republic of Korea.
AB  - In January 2010, foot-and-mouth disease (FMD) occurred for the first time in 8
      years in Korea. The outbreaks were because of A serotype, different from the O
      type, which had occurred previously in 2000 and 2002. The FMD outbreaks were
      identified in seven farms, consisting of six cattle farms where viruses were
      detected and one deer farm where only FMDV antibody was detected. The seven farms
      were within 9.3 km of each other. All susceptible animals within 10 km radius of
      the outbreak farms were placed under movement restrictions for 3-11 weeks. No
      vaccination took place to facilitate the clinical observation of infected animals
      and virus detection. After clinical observations and serological tests within the
      control zones showed no evidence of FMD infection, the movement restrictions were
      lifted, followed by FMD-free declaration (23 March) at 80 days after the first
      outbreak on 2 January. This communication describes the outbreak of FMD A
      serotype, and control measures applied to eradicate the disease in Korea.

PMID- 22630569
TI  - Why a proximity-induced Diels-Alder reaction is so fast.
AB  - Unlike normal Diels-Alder reactions of acyclic alkadienes with alkenes, the
      vinylbicyclo[2.2.2]octene employed in the Baran total synthesis of vinigrol
      undergoes a quantitative Diels-Alder reaction with a tethered alkene at room
      temperature. Density functional theory calculations reveal that this
      unprecedented reactivity originates from a combination of preorganization, diene
      strain, and tether stabilization.

PMID- 22630571
TI  - A case of acquired Zinc deficiency.
AB  - We report a case of adult-onset acquired zinc deficiency after bariatric surgery.
      Zinc deficiency may be inherited in the form of acrodermatitis enteropathica or
      acquired by low nutritional intake, malabsorption, excessive loss of zinc, or a
      combination of these factors.

PMID- 22630572
TI  - Novel approach to utilizing electronic health records for dermatologic research:
      developing a multi-institutional federated data network for clinical and
      translational research in psoriasis and psoriatic arthritis.
AB  - The implementation of Electronic Health Records (EHR) in the United States has
      created new opportunities for research using automated data extraction methods. A
      large amount of information from the EHR can be utilized for clinical and
      translational research. To date, a number of institutions have the capability of
      extracting clinical data from EHR to create local repositories of de-identified
      data amenable to research queries through the Informatics for Integrated Biology
      and the Bedside (i2b2) platform. Collaborations among institutions sharing a
      common i2b2 platform hold exciting opportunities for research in psoriasis and
      psoriatic arthritis. With the automated extraction of patient-level data from
      multiple institutions, this novel informatics network has the ability to address
      high-priority research questions. With commitment to high-quality data through
      applied algorithms for cohort identification and validation of outcomes, the
      creation of Psoriasis and Psoriatic Arthritis Integrated Research Data Network
      (PIONEER) will make a significant contribution to psoriasis and psoriatic
      arthritis research.

PMID- 22630573
TI  - Muir-Torre Syndrome / Turcot Syndrome overlap? A patient with sebaceous
      carcinoma, colon cancer, and a malignant astrocytoma.
AB  - The Muir-Torre Syndrome is characterized by the clinical constellation of
      sebaceous neoplasms, keratoacanthomas, and internal malignancies caused by a
      defect in DNA mismatch repair. Another mismatch repair defect causes Turcot
      syndrome, which manifests with colorectal and central nervous system neoplasms.
      We wish to report a case in which the manifestations of both syndromes were
      observed in the same patient. We further discuss the possible genetic basis for
      this overlap.

PMID- 22630574
TI  - Multiple or familial cafe-au-lait spots is neurofibromatosis type 6:
      clarification of a diagnosis.
AB  - A cafe-au-lait macule (CALM) is an evenly pigmented macule or patch of variable
      size. Solitary CALMs are common birthmarks in up to 2.5 percent of normal
      neonates and their incidence rises to up to 25 percent in preschool-aged
      children. Two or more CALMs occur much less frequently. Multiple lesions may
      warrant investigation to identify an underlying disease including
      neurofibromatosis types 1 (NF1), neurofibromatosis type 2, McCune-Albright
      syndrome, and neurofibromatosis type 1-like syndrome. Considered a hallmark and
      diagnostic criteria for NF1 is the presence of 6 or more CALMs greater than 0.5
      cm in prepubertal individuals. Rare reports describe families which demonstrate
      the phenomenon of multiple CALMs without other stigmata of NF1 or evidence of
      other systemic disease. Herein is a description of the condition and
      justification for this entity to be named Neurofibromatosis type 6.

PMID- 22630576
TI  - Inflammatory myofibroblastic tumor of the tongue: report of an unusual case in a
      teenage patient.
AB  - Inflammatory myofibroblastic tumor is a rare and distinctive lesion composed of
      myofibroblastic cells accompanied by an inflammatory infiltration of plasma
      cells, lymphocytes, and eosinophils that mainly affects viscera and soft tissues
      of children and young adults. It clinically manifests as a mass with rapid
      development that may occur at almost any site of the body, but predominantly in
      the lungs or the upper respiratory tract. It rarely arises in the oral cavity
      with approximately 15 cases reported in that location. We describe a case of an
      inflammatory myofibroblastic tumor of the tongue, confirmed by both
      histopathologic and immunohistochemical analysis, occurring in a 14-year-old boy
      that spontaneously regressed after the surgical procedures for its diagnosis.
      Because of some aggressive clinical, histological, and radiological features,
      this lesion may be confused with a malignant tumor. Therefore, its correct
      recognition is important to avoid unnecessary extensive and radical therapeutic
      approaches.

PMID- 22630575
TI  - Fatal ALK-negative systemic anaplastic large cell lymphoma presenting with
      disseminated cutaneous dome-shaped papules and nodules.
AB  - Anaplastic large cell lymphoma (ALCL) is classified as a CD30 positive non
      Hodgkin lymphoma. Systemic ALCL (S-ALCL) is further subdivided into two subgroups
      based on anaplastic lymphoma kinase (ALK) expression. In systemic ALCL, positive
      ALK expression correlates with a favorable prognosis, whereas negative ALK
      expression correlates with poorer overall survival. By definition, primary
      cutaneous ALCL (cut-ALCL) is limited to the skin and is uniformly ALK-negative.
      Cut-ALCL closely resembles LyP with regards to its benign clinical course and
      CD30 positivity. We describe a unique case of ALK-negative (ALK-) S-ALCL
      presenting with cutaneous disseminated dome-shaped papules.

PMID- 22630577
TI  - Multiple congenital familial smooth muscle hamartoma in two siblings.
AB  - Smooth muscle hamartoma (SMH) is a cutaneous malformation mainly composed of a
      disorganized proliferation of normal muscle fibers that arise from arrector pili.
      It usually presents as a single congenital lesion that frequently involves the
      back and the lower limbs. Unusual clinical presentations, such as atypical
      localizations, multiple disseminated lesions, and generalized forms have been
      rarely described. In 2001, Gualandri et al. reported the presence of multiple SMH
      in three members of the same family, namely two brothers and their mother. This
      is, as far as we know, the only familial case reported in the English literature.
      We herein describe a similar case affecting two siblings who presented with
      identical congenital lesions in the same location.

PMID- 22630578
TI  - Localized blanching erythema in a patient with vulvar carcinoma.
AB  - Mammary-like carcinoma arising in the vulva is a rare type of vulvar malignancy.
      Cutaneous metastasis of vulvar carcinoma is uncommon and the majority of cases
      have been reported in patients with squamous cell carcinoma of the vulva. We
      describe a 69-year-old woman with mammary-like carcinoma of the vulva with
      cutaneous metastasis presenting as asymptomatic localized blanching erythema.

PMID- 22630579
TI  - Extensive cerebriform nevus sebaceus: an unusual presentation.
AB  - Nevus sebaceus is an epidermal nevi composed of sebaceous glands, which usually
      presents as single yellowish plaque over the head and neck. A rare morphological
      variant, namely cerebriform nevus sebaceus was first reported in 1998. As with
      other nevi, the occurrence of nevus sebaceous is related to genetic mosaicism and
      the shape and distribution of the nevus is determined by the stage at which
      mosaicism has arisen. We report a patient with cerebriform nevus sebaceus having
      an unusually widespread distribution over the head, face, and trunk, but without
      any other organ system involvement.

PMID- 22630581
TI  - Linear rays of hypopigmentation following intra-articular corticosteroid
      injection for post-traumatic degenerative joint disease.
AB  - Intra-articular and intralesional glucocorticoid injections are commonly used by
      dermatologists, orthopedic surgeons, and rheumatologists because they offer many
      advantages over oral or parenteral dosage forms. Triamcinalone acetonide is a
      frequently utilized glucocorticosteroid for intra-articular injections, yet there
      are a limited number of case reports describing cutaneous hypopigmentation as an
      adverse effect. Here we present a unique case of hypopigmentation with a linear
      ray distribution demonstrating lymphatic collection and spread of the
      triamcinalone acetonide.

PMID- 22630580
TI  - Verruciform xanthoma: report of two cases.
AB  - Verruciform xanthoma (VX) is an uncommon benign condition of unknown etiology,
      which frequently affects the oral mucosa in adults. Other less common locations
      include the anogenital region and the skin. VX typically presents as an
      asymptomatic plaque showing a verrucous appearance. Histological examination is
      essential for the diagnosis and shows verrucous hyperplasia of the epidermis and
      xanthoma cells limited to the dermal papillae. We present herein two cases of VX
      and discuss the histopathological findings and possible correlation with a
      postulated etio-pathogenesis.

PMID- 22630582
TI  - Cutaneous metastasis of renal cell carcinoma: a case report.
AB  - Cutaneous metastasis develops in 5 to 10 percent of high-stage cancer patients.
      About 6 percent of cutaneous metastases are caused by renal cell carcinomas
      (RCC). A 64-year-old man presented with a 4-month history of a rapidly enlarging
      lesion on the mental region. There was a 2 cm x 3 cm multilobular and polypoid
      angiomatous tumor in the center of the swelling. Histopathologic examination
      revealed clear cell proliferation with gland formation and red blood cell (RBC)
      extravasation, compatible with metastatic renal cell carcinoma. The rich vascular
      structure of RCCs facilitates hematogenous extension and the development of
      distant metastasis. Arteriovenous and systemic shunts are thought to facilitate
      the tumor cells' path to the head and neck region. RCC cutaneous metastasis is
      known to have a vascular appearance. It is important to consider RCC metastasis
      in the differential diagnosis of new onset tumors with a vascular appearance in
      the head and neck region.

PMID- 22630583
TI  - Lupus vulgaris diagnosed after 37 years: a case of delayed diagnosis.
AB  - Lupus vulgaris is the most common chronic, progressive form of cutaneous
      tuberculosis. Lesions are generally solitary and found on the head and neck
      region. Cutaneous tuberculosis can present with different clinical appearances.
      Therefore, it does not necessarily have characteristic findings and can be
      difficult to diagnose. Although there were typical clinical findings, the
      diagnosis of our case was delayed because of its asymptomatic course.

PMID- 22630584
TI  - Acetylcholine receptor antibodies in patients with pemphigus vulgaris:
      correlation with disease extent at the time of diagnosis and during follow-up.
AB  - Several studies have tried to determine the relationship between autoantibodies
      against the acetylcholine receptor and the development of pemphigus vulgaris. In
      this study, we observed that antibody levels against the acetylcholine receptor
      are mildly elevated in pemphigus vulgaris (PV), and significantly correlate with
      disease severity on the initial diagnosis and during follow up. However, it is
      not clear if these antibodies are just an epiphenomenon or a potential trigger of
      the known pathogenic process in PV.

PMID- 22630585
TI  - Hyaluronic acid filler for a depressed scar.
AB  - The use of filler for depressed scars has been documented but is rare in the
      literature. We present a case of a patient treated with hyaluronic acid fillers
      at the site of a long-standing depressed scar.

PMID- 22630586
TI  - Purpuric drug eruption and alopecia induced by erlotinib.
AB  - We herein report a case of diffuse alopecia with pustules on the scalp and
      purpuric lesions on the lower legs in a Japanese man after treatment with
      erlotinib. This is a unique case in which rare skin eruptions simultaneously
      occurred. We discuss herein a combination of skin eruptions as an adverse
      reaction of epidermal growth factor-receptor (EGF-R) tyrosine kinase inhibitor.
      It is indispensable to be aware of rare skin reactions when applying molecular
      targeting therapies.

PMID- 22630587
TI  - Accurate description of aqueous carbonate ions: an effective polarization model
      verified by neutron scattering.
AB  - The carbonate ion plays a central role in the biochemical formation of the shells
      of aquatic life, which is an important path for carbon dioxide sequestration.
      Given the vital role of carbonate in this and other contexts, it is imperative to
      develop accurate models for such a high charge density ion. As a divalent ion,
      carbonate has a strong polarizing effect on surrounding water molecules. This
      raises the question whether it is possible to describe accurately such systems
      without including polarization. It has recently been suggested the lack of
      electronic polarization in nonpolarizable water models can be effectively
      compensated by introducing an electronic dielectric continuum, which is with
      respect to the forces between atoms equivalent to rescaling the ionic charges.
      Given how widely nonpolarizable models are used to model electrolyte solutions,
      establishing the experimental validity of this suggestion is imperative. Here, we
      examine a stringent test for such models: a comparison of the difference of the
      neutron scattering structure factors of K2CO3 vs KNO3 solutions and that
      predicted by molecular dynamics simulations for various models of the same
      systems. We compare standard nonpolarizable simulations in SPC/E water to
      analogous simulations with effective ion charges, as well as simulations in
      explicitly polarizable POL3 water (which, however, has only about half the
      experimental polarizability). It is found that the simulation with rescaled
      charges is in a very good agreement with the experimental data, which is
      significantly better than for the nonpolarizable simulation and even better than
      for the explicitly polarizable POL3 model.

PMID- 22630588
TI  - Oral lesions in elderly patients of a community in Brazilian Northeast.
AB  - OBJECTIVE: To investigate the oral soft-tissue injuries in people aged 60 or
      older. METHODS: Cross-sectional research conducted with 262 elders aged 60-93
      years (mean 69.84, SD +/- 6.212) from the Dende community in Northeast, Brazil.
      Data were collected through an identification questionnaire and the Community
      Indicator in Oral Health. Data were computed by the Software SPSS, version 15.
      RESULTS: There was a predominance of female gender (64.1%), retired, low
      schooling and income of up to one minimum wage. It was detected a prevalence of
      soft-tissue injuries in 38.4% (n = 101) of the elders, distributed as follows:
      red spots 60(57.7%), blisters 20(19.2%), lesions and/or wound 16(15.4%), and
      white spot 8(7.7%). Among the elders, 40(15.3%) smoked and 20(7.6%) used alcohol.
      It was verified a statistical association between injuries and using prosthesis
      (p = 0.039), medicine (p = 0.023) and calculus (p = 0.016). CONCLUSION: The oral
      health of this population is precarious, and there is a high prevalence of oral
      lesions.

PMID- 22630590
TI  - Biological Macromolecular Dynamics.

PMID- 22630591
TI  - Journal of Biomolecular Structure and Dynamics.

PMID- 22630589
TI  - Persian translation and validation of the Kujala Patellofemoral Scale in patients
      with patellofemoral pain syndrome.
AB  - PURPOSE: To culturally translate and validate the Persian version of Kujala
      Patellofemoral Scale (KPS) and evaluate the test-retest reliability, internal
      consistency, construct validity and ceiling or floor effects of this instrument
      in patients with patellofemoral pain syndrome (PFPS). METHOD: After standard
      forward and backward translations, 100 patients with PFPS completed the Persian
      versions of the KPS and Short-Form 36 Health Survey (SF-36) in the first visit.
      With time interval of 2-3 days after the first visit, 47 patients filled out the
      KPS in the second visit. Test-retest reliability and internal consistency were
      assessed using intraclass correlation coefficient (ICC(2,1)) with 95% confidence
      interval (95% CI) and Cronbach's alpha coefficient, respectively. The Spearman's
      rank correlation (r(s)) was used to assess the correlations between the Persian
      KPS and SF-36 subscales. RESULTS: The acceptable level of ICC >0.70 (ICC = 0.96,
      95% CI = 0.93-0.98) and Cronbach's alpha coefficient >0.70 (alpha = 0.81) was
      obtained for the Persian KPS. There were low to moderate correlations (r(s) =
      0.25-0.60, p < .01) between the Persian KPS and Persian SF-36 subscales of mental
      and physical health components. However, correlations between the Persian KPS and
      SF-36 physical components were higher than correlations between the Persian KPS
      and SF-36 mental components. No ceiling and floor effects were seen for the
      Persian KPS. CONCLUSIONS: The Persian version of KPS is a reliable and valid
      outcome measure of disability and seems to be a suitable instrument for use in
      clinical practice of Iranian patients with chronic PFPS.

PMID- 22630593
TI  - Structural Biology: The State of the Art.

PMID- 22630592
TI  - Biological Structure and Dynamics.

PMID- 22630595
TI  - High-throughput discovery of novel steric stabilizers for cubic lyotropic liquid
      crystal nanoparticle dispersions.
AB  - High-throughput methodologies have been employed to establish structure-property
      relationships and assess the effectiveness of nonionic steric stabilizers for
      inverse bicontinuous cubic lyotropic liquid crystalline nanoparticulate
      dispersions of monoolein and phytantriol. The ability of the stabilizers to
      disperse the lipids was compared with that of the commonly employed triblock
      poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) copolymer
      Pluronic F127, which was used as a positive control. The poly(ethylene oxide)
      stearate class of stabilizers (commercially known as Myrj) were discovered to be
      effective as steric stabilizers for cubosomes, while retaining the internal
      nanostructure of the "parent" bulk phase. In particular, Myrj 59, with an average
      of 100 poly(ethylene oxide) units, was more effective than F127 at dispersing
      phytantriol, forming stable phytantriol cubosome dispersions at a concentration
      of 0.1 wt %, 5-fold lower than that achievable with Pluronic F127. The discovery
      of this new effective class of stabilizers for cubosomes, specifically enabled by
      high-throughput approaches, broadens the versatility of components from which to
      construct these interesting potential drug delivery and medical imaging
      nanoparticles.

PMID- 22630597
TI  - Radiographic lymphangiography in the dog using iodized oil.
AB  - The objective of this study was to develop a clinically applicable technique to
      visualize the medial retropharyngeal, superficial cervical, axillary, superficial
      inguinal and medial iliac lymph nodes on radiographs. Direct and indirect
      lymphangiographic methods using iodized oil were repeated for a minimum of five
      times at eight different locations to enhance the various lymph nodes, using 16
      healthy research dogs. Direct lymphangiography, although more invasive than
      indirect lymphangiography, resulted in uniform contrast uptake by an increased
      number of nodes and increased enhancement of the lymphatic vasculature, and is
      recommended for imaging the medial iliac and superficial cervical lymph nodes.
      Side effects were more frequent after indirect lymphangiography (10/20 injection
      sites) than after direct lymphangiography (3/16 injection sites). The small size
      of afferent lymphatic vessels did not allow use of direct lymphangiography for
      the medial retropharyngeal, axillary and superficial inguinal lymph nodes;
      however, indirect techniques allowed adequate visualization of these nodes.

PMID- 22630596
TI  - Carcinoembryonic antigen (CEA)-based cancer vaccines: recent patents and
      antitumor effects from experimental models to clinical trials.
AB  - Carcinoembryonic antigen (CEA), a glycosylated protein of MW 180 kDa, is
      overexpressed in a wide range of human carcinomas, including colorectal, gastric,
      pancreatic, non-small cell lung and breast carcinomas. Accordingly, CEA is one of
      several oncofetal antigens that may serve as a target for active anti-cancer
      specific immunotherapy. Experimental results obtained by employing animal models
      have supported the design of clinical trials using a CEA-based vaccine for the
      treatment of different types of human cancers. This review reports findings from
      experimental models and clinical evidence on the use of a CEA-based vaccine for
      the treatment of cancer patients. Among the diverse CEA-based cancer vaccines,
      DCs- and recombinant viruses-based vaccines seem the most valid. However,
      although vaccination was shown to induce a strong immune response to CEA,
      resulting in a delay in tumor progression and prolonged survival in some cancer
      patients, it failed to eradicate the tumor in most cases, owing partly to the
      negative effect exerted by the tumor microenvironment on immune response. Thus,
      in order to develop more efficient and effective cancer vaccines, it is necessary
      to design new clinical trials combining cancer vaccines with chemotherapy,
      radiotherapy and drugs which target those factors responsible for
      immunosuppression of immune cells. This review also discusses relevant patents
      relating to the use of CEA as a cancer vaccine.

PMID- 22630598
TI  - Disability beliefs and help-seeking behavior of depressed Chinese-American
      patients in a primary care setting.
AB  - In this study the authors assessed the effects of disability beliefs,
      conceptualization and labeling of emotional disabilities, and perceived barriers
      on help-seeking behaviors among depressed Chinese Americans in a primary care
      setting. Forty-two Chinese Americans participated in semistructured interviews
      using established psychological measures and open-ended questions adapted from
      the Explanatory Model Interview Catalogue. The authors found that care
      utilization appears to be complicated by somatization of emotional problems,
      variations in causal attribution to depression, barriers to receiving mental
      health care, and the burden of comorbid physical conditions. Their findings
      highlight the importance of addressing these issues and educating patients about
      body-mind dialectic common to depression.

PMID- 22630599
TI  - Perceptions about disability among Ghanaian university students.
AB  - An exploratory/descriptive study was conducted on a sample of university
      students, including 305 social work and sociology majors, in Ghana to evaluate
      their attitudes toward disabilities. The findings indicate that the students in
      general agree with the idea of community integration and equal rights of persons
      with disabilities. At the same time, they are ambivalent about characteristics of
      persons with disabilities and feel uncomfortable interacting with them. Further,
      a substantive minority holds strong prejudices against persons with disabilities.
      Universities should provide their students with opportunities to improve
      knowledge and attitudes about disabilities.

PMID- 22630600
TI  - Enjoying work or burdened by it? How personal assistants experience and handle
      stress at work.
AB  - A personal assistant has to promote equality in living conditions for persons
      with severe disabilities. The aim of this study was to explore how personal
      assistants experience their work and what strategies they employ to alleviate
      work-related stress. Thirty personal assistants were interviewed and latent
      content analysis was performed. The findings regarding the experiences of work
      related stress could be brought together under the theme of "difficulties of
      being in a subordinate position," and those regarding management strategies could
      be brought together under the theme of "coming to terms with the work situation."
      There is a need to empower personal assistants through training programs
      including tailored education, working communities, and coaching.

PMID- 22630601
TI  - Functional disability among chronic pain patients receiving long-term opioid
      treatment.
AB  - This study of 2,163 adult chronic, non-cancer-pain, long-term opioid therapy
      patients examines the relationship of depression to functional disability by
      measuring average pain interference, activity limitation days, and employment
      status. Those with more depression symptoms compared to those with fewer were
      more likely to have worse disability on all 3 measures (average pain interference
      score >5, OR = 5.36, p < .0001; activity limitation days >= 30, OR = 4.05, p <
      .0001; unemployed due to health reasons, OR = 4.06, p < .0001). Depression might
      play a crucial role in the lives of these patients; identifying and treating
      depression symptoms in chronic pain patients should be a priority.

PMID- 22630602
TI  - Influence of the curing mode on the degree of conversion of a dual-cured self
      adhesive resin luting cement beneath ceramic.
AB  - OBJECTIVE: To evaluate the effect of the delayed photoactivation and ceramic
      barrier on the degree of conversion (DC) of self-adhesive resin cement. MATERIALS
      AND METHODS: Circular specimens (5 mm in diameter * 1 mm in thickness) of the
      RelyX U-100 resin cement were made using the following curing protocols (n = 10):
      (G1) 40 s beneath a IPS Empress II ceramic; (G2) 40 s of direct photocuring; (G3)
      80 s beneath the ceramic; (G4) 80 s of direct photocuring; (G5) self-curing; (G6)
      5 min in the absence of light (self-curing) followed by transceramic photocuring
      for 40 s; (G7) 5 min in the absence of light (self-curing) followed by
      transceramic photocuring for 80 s. All the specimens were photoactivated by LED
      (800 mW/cm(2)). After 24 h of dry storage, the DC was measured by FTIR, on the
      top surface of the specimens. Data were submitted to one-way ANOVA and Tukey test
      (p <= 0.05). RESULTS: Direct photocuring with no ceramic interposition,
      regardless of the curing time (40 s and 80 s) promoted the highest conversion
      mean (56.79 +/- 1.19 and 59.98 +/- 2.93, respectively) and the 5 min delay time
      for the transceramic photocuring presented a similar mean compared to the
      immediate transceramic photocuring. The DC was influenced by the ceramic barrier,
      decreasing the conversion values (49.72 +/- 1.91 for 40 s and 52.36 +/- 2.50 for
      80 s), with no statistical difference from the groups with the previous 5 min of
      photoactivation delay. The self-cure only showed the worst DC values. CONCLUSION:
      Direct photocuring provided a higher degree of conversion for the self-adhesive
      resin cement. The delayed light activation did not influence the degree of
      conversion for the resin cement tested.

PMID- 22630603
TI  - [Can women be defined by the freedom of motherhood choice?].

PMID- 22630604
TI  - Reversible light-directed red, green, and blue reflection with thermal stability
      enabled by a self-organized helical superstructure.
AB  - Adding external, remote, and dynamic control to self-organized superstructures
      with desired properties is an important leap necessary in leveraging the
      fascinating molecular subsystems for employment in applications. Here two novel
      light-driven dithienylethene chiral molecular switches possessing remarkable
      changes in helical twisting power during photoisomerization as well as very high
      helical twisting powers were found to experience photochemically reversible
      isomerization with thermal stability in both isotropic organic solvents and
      anisotropic liquid crystal media. When doped into a commercially available
      achiral liquid crystal host, the chiral switch was able to either immediately
      induce an optically tunable helical superstructure or retain an achiral
      photoresponsive liquid crystal phase whose helical superstructure was induced and
      tuned reversibly upon light irradiation. Moreover, reversible light-directed red,
      green, and blue reflection colors with thermal stability in a single thin film
      were demonstrated.

PMID- 22630605
TI  - Contribution of partial charge interactions and base stacking to the efficiency
      of primer extension at and beyond abasic sites in DNA.
AB  - During DNA synthesis, base stacking and Watson-Crick (WC) hydrogen bonding
      increase the stability of nascent base pairs when they are in a ternary complex.
      To evaluate the contribution of base stacking to the incorporation efficiency of
      dNTPs when a DNA polymerase encounters an abasic site, we varied the penultimate
      base pairs (PBs) adjacent to the abasic site using all 16 possible combinations.
      We then determined pre-steady-state kinetic parameters with an RB69 DNA
      polymerase variant and solved nine structures of the corresponding ternary
      complexes. The efficiency of incorporation for incoming dNTPs opposite an abasic
      site varied between 2- and 210-fold depending on the identity of the PB. We
      propose that the A rule can be extended to encompass the fact that DNA polymerase
      can bypass dA/abasic sites more efficiently than other dN/abasic sites. Crystal
      structures of the ternary complexes show that the surface of the incoming base
      was stacked against the PB's interface and that the kinetic parameters for dNMP
      incorporation were consistent with specific features of base stacking, such as
      surface area and partial charge-charge interactions between the incoming base and
      the PB. Without a templating nucleotide residue, an incoming dNTP has no base
      with which it can hydrogen bond and cannot be desolvated, so that these
      surrounding water molecules become ordered and remain on the PB's surface in the
      ternary complex. When these water molecules are on top of a hydrophobic patch on
      the PB, they destabilize the ternary complex, and the incorporation efficiency of
      incoming dNTPs is reduced.

PMID- 22630606
TI  - Continual Gram-negative bacterial challenge accelerates stroke onset in stroke
      prone spontaneously hypertensive rats.
AB  - This study examined the effects of continual Gram-negative bacterial challenge on
      stroke onset. Stroke onset occurred significantly earlier in stroke-prone
      spontaneously hypertensive rats (SHRSP) injected with a bacterial cell suspension
      of Gram-negative rods or lipopolysaccharides (LPSs) than in uninjected controls.
      Paralysis of the hindlimb, piloerection, hypokinesis, and hyperkinesis were
      observed in LPS-injected SHRSP but not in uninjected controls during stroke
      onset. The serum levels of NOx, thiobarbituric acid reactive substance, and 8
      hydroxydeoxyguanosine increased in LPS-injected SHRSP. These results suggest that
      continual Gram-negative bacterial challenge induces accelerated stroke onset in
      SHRSP, probably caused by oxidative stress responses derived from LPSs.

PMID- 22630607
TI  - The acceptability, feasibility and impact of a lay health counsellor delivered
      health promoting schools programme in India: a case study evaluation.
AB  - BACKGROUND: Studies in resource-limited settings have shown that there are
      constraints to the use of teachers, peers or health professionals to deliver
      school health promotion interventions. School health programmes delivered by
      trained lay health counsellors could offer a cost-effective alternative. This
      paper presents a case study of a multi-component school health promotion
      intervention in India that was delivered by lay school health counsellors, who
      possessed neither formal educational nor health provider qualifications. METHODS:
      The intervention was based on the WHO's Health Promoting Schools framework, and
      included health screening camps; an anonymous letter box for student questions
      and complaints; classroom-based life skills training; and, individual psycho
      social and academic counselling for students. The intervention was delivered by a
      lay school health counsellor who had attained a minimum of a high school
      education. The counsellor was trained over four weeks and received structured
      supervision from health professionals working for the implementing NGO. The
      evaluation design was a mixed methods case study. Quantitative process indicators
      were collected to assess the extent to which the programme was delivered as
      planned (feasibility), the uptake of services (acceptability), and the number of
      students who received corrective health treatment (evidence of impact). Semi
      structured interviews were conducted over two years with 108 stakeholders, and
      were analysed to identify barriers and facilitators for the programme
      (feasibility), evaluate acceptability, and gather evidence of positive or
      negative effects of the programme. RESULTS: Feasibility was established by the
      high reported coverage of all the targeted activities by the school health
      counsellor. Acceptability was indicated by a growing number of submissions to the
      students' anonymous letter-box; more students self-referring for counselling
      services over time; and, the perceived need for the programme, as expressed by
      principals, parents and students. A minority of teachers complained that there
      was inadequate information sharing about the programme and mentioned reservations
      about the capacities of the lay health counsellor. Preliminary evidence of the
      positive effects of the programme included the correction of vision problems
      detected in health screening camps, and qualitative evidence of changes in health
      related knowledge and behaviour of students. CONCLUSION: A task-shifting approach
      of delegating school health promotion activities to lay school health counsellors
      rather than education or health professionals shows promise of effectiveness as a
      scalable model for promoting the health and well being of school based
      adolescents in resource constrained settings.

PMID- 22630608
TI  - Inflammatory infiltration of metaplastic epithelium and correlation to previous
      diagnosis of esophagitis and Barrett's length.
AB  - OBJECTIVE: The contact of the gastric refluxate with the lower esophagus results
      in an inflammatory-mediated tissue damage. The role of inflammation both in the
      development and in the advance of Barrett's esophagus (BE) has not been
      elucidated. The aim of this study was to assess the inflammatory infiltration in
      metaplastic Barrett's epithelium and to explore the association of microscopic
      inflammation to healed esophagitis and Barrett's length. MATERIAL AND METHODS:
      Inflammatory infiltration was qualitatively evaluated in well-characterized
      Barrett's specimens. Esophagitis was healed prior to histological sampling.
      Univariate comparative analysis was performed based on BE length. RESULTS: Ninety
      eight patients (78 male, mean age 58.3 +/- 13.3 yrs) were retrospectively
      studied. Thirty-three cases with long segment BE (LSBE) (33.7%) were spotted.
      Inflammatory infiltration was mild, moderate, and severe in 35 (35.7%), 54
      (55.1%), and 9 (9.1%) specimens, respectively. The samples with moderate/severe
      inflammatory infiltration were obtained from patients who had more frequently
      been diagnosed with esophagitis (p = 0.025). Hiatal hernia (p = 0.001),
      esophagitis (p = 0.019), and previous use of anti-secretory drugs (p = 0.005)
      were more common in LSBE. CONCLUSIONS: Inflammatory infiltration of Barrett's
      epithelium was largely moderate despite preceding healing of erosions with PPIs.
      Previous diagnosis of esophagitis correlated to the degree of inflammation. No
      association of inflammation to Barrett's length was established.

PMID- 22630609
TI  - Glanders in animals: a review on epidemiology, clinical presentation, diagnosis
      and countermeasures.
AB  - Glanders or farcy, caused by Burkholderia mallei, is an infectious and zoonotic
      disease of solipeds. Horses, donkeys and mules are the only known natural
      reservoir of B. mallei. Although glanders has been eradicated from most
      countries, it has regained the status of a re-emerging disease because of the
      numerous recent outbreaks. Pre-symptomatic or carrier animals are the potential
      source of infection for the healthy equine population and play a crucial role in
      the spreading of the infectious agent. Glanders is characterized by ulcerating
      nodular lesions of the skin and mucous membrane. Generalized symptoms include
      fever, malaise, depression, cough, anorexia and weight loss. Burkholderia mallei
      can invade its host through mucous membranes, gastrointestinal tract and the
      integument. Its virulence mechanisms and pathogenesis are not yet completely
      understood. A major problem when using serological tests for diagnosing glanders
      is the occurrence of false-positive and false-negative results leading to
      difficulties in international trade with equids and to the spread of glanders to
      disease-free regions. Moreover, poor tests critically result in poor control of
      disease. These tests are not only incapable of discriminating between B. mallei
      and B. pseudomallei antibodies, they are also unable to differentiate between
      malleinized and naturally infected animals. Combined use of both serological and
      molecular detection methods increases the detection rate of glanders.
      Countermeasures against glanders include early detection of disease in
      susceptible animals, stringent quarantine measures, testing and safe destruction
      of infected carcasses, adequate compensation to the animal owners, disinfection
      of infected premises and awareness about glanders and the zoonotic implications
      through veterinary extension services. An account of the clinical picture and
      successful experimental therapy of spontaneous equine glanders is also given.

PMID- 22630610
TI  - Rapid and robust detection methods for poison and microbial contamination.
AB  - Real-time on-site monitoring of analytes is currently in high demand for food
      contamination, water, medicines, and ingestible household products that were
      never tested appropriately. Here we introduce chemical methods for the rapid
      quantification of a wide range of chemical and microbial contaminations using a
      simple instrument. Within the testing procedure, we used a multichannel,
      multisample, UV-vis spectrophotometer/fluorometer that employs two frequencies of
      light simultaneously to interrogate the sample. We present new enzyme- and dye
      based methods to detect (di)ethylene glycol in consumables above 0.1 wt % without
      interference and alcohols above 1 ppb. Using DNA intercalating dyes, we can
      detect a range of pathogens ( E. coli , Salmonella , V. Cholera, and a model for
      Malaria) in water, foods, and blood without background signal. We achieved
      universal scaling independent of pathogen size above 10(4) CFU/mL by taking
      advantage of the simultaneous measurement at multiple wavelengths. We can detect
      contaminants directly, without separation, purification, concentration, or
      incubation. Our chemistry is stable to +/- 1% for >3 weeks without refrigeration,
      and measurements require <5 min.

PMID- 22630611
TI  - Effect of opium dependency on secondary intention wound healing in a rat model:
      an experimental study.
AB  - Opium dependency is a social and health problem in some middle eastern countries
      like Iran. Many of these people may require surgery. This study investigates the
      effects of opium dependency on histological parameters of secondary intention
      wound healing in rat. A full-thickness wound (2 * 2 cm in diameters) was created
      on the dorsum of two groups of rats, a normal control group and a second group of
      rat depended to opium (Badawy's method). Several times during 14 days
      postwounding, the wound was excised with peripheral margins of normal skin and
      was evaluated for cellular population, reepithelialisation and revascularisation.
      Results are presented as the mean +/- standard error. Data were compared by an
      unpaired t-test or analysis of variance. Histological examination of the wound
      tissue showed evidence of increased population of fibroblasts, decreased
      recruitment of neutrophile and plateau of macrophage cells in opium depended
      animals comparing with control group. In the depended animals,
      reepithelialisation was seen to be enhanced significantly, while prohibiting
      progression of revascularisation. This study shows that opium dependency enhances
      reepitheliazation as well as tissue recruitment of fibroblasts; thereby probable
      enhancement of secondary intention wound healing.

PMID- 22630612
TI  - The impact of sport on children with haemophilia.
AB  - Sport is nowadays perceived as beneficial for children with haemophilia, as good
      muscle strength supports joints and may reduce bleed frequency; by contrast
      psychological benefits are less known. This study introduces the impact of sport
      on health-related quality of life (HRQoL) and physical performance in children
      with haemophilia. A cross-sectional, multi-site, study of boys aged 6-17 years
      with haemophilia A or B of any severity, current or past inhibitor, which
      assessed physical performance, sporting activity and HRQoL using age appropriate
      questionnaires including KINDL, Haemo-QoL and HEP-Test-Q. Eighty-four haemophilic
      boys (23 mild, 19 moderate, 42 severe) with a mean age of 11.52 years (SD = 3.4)
      were enrolled from two haemophilia centres in the United Kingdom. 28.4% were
      overweight/obese according to their BMI/age and had a good orthopaedic status (M
      = 1.55, SD = 3.3). Boys watching < 1-2 h of TV/PC/day had fewer days lost (M = 3,
      SD = 3.2) than those with a more sedentary lifestyle (M = 9.40, SD = 7.1) (P <
      0.032). 90.5% participated in regular sporting activity; 79.9% at least twice a
      week. HRQoL in children was generally good, with highest impairments in boys aged
      8-12 years. Boys aged 8-16 years reported good physical performance (M = 80.0, SD
      = 16.0) with highest impairments in the dimensions 'endurance' and 'mobility'.
      Boys doing sport had a significant better physical performance and HRQoL than
      boys not doing sport. Sedentary life styles had a negative impact on the
      subjective physical performance and number of days lost of children. Encouraging
      haemophilic boys to participate in sport will have a direct impact on their
      overall HRQoL.

PMID- 22630614
TI  - Structures and dissociation channels of protonated mixed clusters around a small
      magic number: infrared spectroscopy of ((CH3)3N)n-H(+)-H2O (n = 1-3).
AB  - The magic number behavior of ((CH(3))(3)N)(n)-H(+)-H(2)O clusters at n = 3 is
      investigated by applying infrared spectroscopy to the clusters of n = 1-3.
      Structures of these clusters are determined in conjunction with density
      functional theory calculations. Dissociation channels upon infrared excitation
      are also measured, and their correlation with the cluster structures is examined.
      It is demonstrated that the magic number cluster has a closed-shell structure, in
      which the water moiety is surrounded by three (CH(3))(3)N molecules. The ion core
      (protonated site) of the clusters is found to be (CH(3))(3)NH(+) for n = 1-3, but
      coexistence of an isomer of the H(3)O(+) ion core cannot be ruled out for n = 3.
      Large rearrangement of the cluster structures of n = 2 and 3 before dissociation,
      which has been suggested in the mass spectrometric studies, is confirmed on the
      basis of the structure determination by infrared spectroscopy.

PMID- 22630615
TI  - Carrot and stick--a novel policy experiment of transboundary watershed protection
      in China.

PMID- 22630613
TI  - The thoracolumbar fascia: anatomy, function and clinical considerations.
AB  - In this overview, new and existent material on the organization and composition
      of the thoracolumbar fascia (TLF) will be evaluated in respect to its anatomy,
      innervation biomechanics and clinical relevance. The integration of the passive
      connective tissues of the TLF and active muscular structures surrounding this
      structure are discussed, and the relevance of their mutual interactions in
      relation to low back and pelvic pain reviewed. The TLF is a girdling structure
      consisting of several aponeurotic and fascial layers that separates the
      paraspinal muscles from the muscles of the posterior abdominal wall. The
      superficial lamina of the posterior layer of the TLF (PLF) is dominated by the
      aponeuroses of the latissimus dorsi and the serratus posterior inferior. The
      deeper lamina of the PLF forms an encapsulating retinacular sheath around the
      paraspinal muscles. The middle layer of the TLF (MLF) appears to derive from an
      intermuscular septum that developmentally separates the epaxial from the hypaxial
      musculature. This septum forms during the fifth and sixth weeks of gestation. The
      paraspinal retinacular sheath (PRS) is in a key position to act as a 'hydraulic
      amplifier', assisting the paraspinal muscles in supporting the lumbosacral spine.
      This sheath forms a lumbar interfascial triangle (LIFT) with the MLF and PLF.
      Along the lateral border of the PRS, a raphe forms where the sheath meets the
      aponeurosis of the transversus abdominis. This lateral raphe is a thickened
      complex of dense connective tissue marked by the presence of the LIFT, and
      represents the junction of the hypaxial myofascial compartment (the abdominal
      muscles) with the paraspinal sheath of the epaxial muscles. The lateral raphe is
      in a position to distribute tension from the surrounding hypaxial and extremity
      muscles into the layers of the TLF. At the base of the lumbar spine all of the
      layers of the TLF fuse together into a thick composite that attaches firmly to
      the posterior superior iliac spine and the sacrotuberous ligament. This
      thoracolumbar composite (TLC) is in a position to assist in maintaining the
      integrity of the lower lumbar spine and the sacroiliac joint. The three
      dimensional structure of the TLF and its caudally positioned composite will be
      analyzed in light of recent studies concerning the cellular organization of
      fascia, as well as its innervation. Finally, the concept of a TLC will be used to
      reassess biomechanical models of lumbopelvic stability, static posture and
      movement.

PMID- 22630616
TI  - A pilot randomised controlled trial of modafinil during acute methamphetamine
      withdrawal: feasibility, tolerability and clinical outcomes.
AB  - INTRODUCTION AND AIMS: There are no medications approved for the treatment of
      methamphetamine withdrawal. Wake-promoting agent modafinil has recently been
      proposed as a viable option. This paper reports on the results of a pilot study
      that tested the feasibility of modafinil in an inpatient withdrawal setting
      during acute methamphetamine withdrawal. DESIGN AND METHODS: In a double-blind,
      randomised, placebo-controlled study, 19 methamphetamine dependent participants
      received modafinil (n = 9) or placebo (n = 10) daily for 7 days (200 mg for the
      first 5 days and 100 mg on days 6 and 7). Primary outcomes were retention in
      treatment and severity of withdrawal symptoms. Secondary outcomes were
      methamphetamine craving, sleep and physiological outcomes. RESULTS: There were no
      significant differences between groups on retention in treatment, withdrawal
      severity, craving, sleep or physiological outcomes. There were no adverse events
      or side-effects reported. CONCLUSIONS: Modafinil was found to be tolerable and
      well accepted by methamphetamine users and feasible for short-term inpatient
      withdrawal, but the sample was too small to detect treatment effects. Larger
      trials are needed to establish efficacy.

PMID- 22630782
TI  - The combination of FRAX and Ageing Male Symptoms scale better identifies treated
      HIV males at risk for major fracture.
AB  - OBJECTIVE: Osteoporosis and hypogonadism are common in men with HIV infection.
      Ageing Male Symptoms (AMS) scale measures symptoms related to hypogonadism. FRAX
      provides 10-year probability of major fractures. We investigated the role of AMS
      scale combined with FRAX without bone mineral density (BMD), in identifying HIV
      men with bone fragility. DESIGN: Cross-sectional observational study. METHODS:
      Fifty HIV-positive men treated with highly active antiretroviral therapy and 27
      controls underwent hormonal evaluation, BMD scan and spine X-ray. The AMS
      questionnaire was administered. RESULTS: Osteoporosis was found in 24.0% of HIV
      patients and in 3.7% of controls (P = 0.05). In HIV patients, 9 radiological
      vertebral fractures were found (none in controls, P = 0.04). Calculated free
      testosterone suggested hypogonadism in 26% of HIV patients vs 4% of controls (P =
      0.04); an abnormal AMS score (>=27) was found in 62% HIV patients compared with
      41% controls (P = 0.04). ROC curves showed that FRAX for major fracture had a 23%
      sensitivity and a 100% specificity in identifying HIV patients with bone
      fragility (P = 0.002, with the threshold of 7% at which bisphosphonate therapy is
      cost-effective). Considering a value of AMS >=27, we obtained an 82.6%
      sensitivity and a 42.9% specificity (P = 0.04). The combination of AMS and FRAX
      score achieved a 77.3% sensitivity and a 69% specificity (P = 0.02, cut-off 34).
      CONCLUSION: Combination of FRAX (without BMD) and AMS improved sensitivity of
      FRAX alone in identifying HIV patients at fracture risk, at the expense of
      reduced specificity.

PMID- 22630783
TI  - Stepwise cyanation of naphthalene diimide for n-channel field-effect transistors.
AB  - Stepwise cyanation of tetrabromonaphthalenediimide (NDI) 1 gave a series of
      cyanated NDIs 2-5 with the monocyanated NDI 2 and dicyanated NDI 3 isolated. The
      tri- and tetracyano- NDIs 4 and 5 show intrinsic instability toward moisture
      because of their extremely low-lying LUMO energy levels. The partially cyanated
      intermediates can be utilized as air-stable n-type semiconductors with OFET
      electron mobility up to 0.05 cm(2) V(-1) s(-1).

PMID- 22630784
TI  - Magnitude and accuracy differences between judgements of remembering and
      forgetting.
AB  - Metacognition researchers have recently begun to examine the effects of framing
      judgements of learning (JOLs) in terms of forgetting (rather than remembering) on
      the judgements' magnitude and accuracy. Although a promising new direction for
      the study of metamemory, initial studies have yielded inconsistent results. To
      help resolve these inconsistencies, in four experiments we had college students
      (N = 434) study paired associates and make JOLs framed in terms of either
      remembering or forgetting over two study-test trials. Our goals were to further
      document the effects of framing on the magnitude and accuracy of JOLs and to
      consider explanations for why specific patterns tend to emerge. The present
      experiments provide evidence that (a) judgements of forgetting are
      psychologically anchored at the midpoint of the JOL scale, whereas judgements of
      remembering are anchored at a lower point, (b) differences in absolute accuracy
      (calibration) by frame are largely artefactual and stem from differences in
      anchoring, (c) differences in JOL magnitude and absolute accuracy by frame do not
      obtain when memory cues are salient to participants, and (d) a forget frame
      impairs the relative accuracy (resolution) of JOLs across trials by reducing
      participants' reliance on cues such as memory for past test performance.

PMID- 22630787
TI  - Hybrid surface design for robust superhydrophobicity.
AB  - Surfaces may be rendered superhydrophobic by engineering the surface morphology
      to control the extent of the liquid-air interface and by the use of low-surface
      energy coatings. The droplet state on a superhydrophobic surface under static and
      dynamic conditions may be explained in terms of the relative magnitudes of the
      wetting and antiwetting pressures acting at the liquid-air interface on the
      substrate. In this paper, we discuss the design and fabrication of hollow hybrid
      superhydrophobic surfaces which incorporate both communicating and
      noncommunicating air gaps. The surface design is analytically shown to exhibit
      higher capillary (or nonwetting) pressure compared to solid pillars with only
      communicating air gaps. Six hybrid surfaces are fabricated with different surface
      parameters selected such that the Cassie state of a droplet is energetically
      favorable. The robustness of the surfaces is tested under dynamic impingement
      conditions, and droplet dynamics are explained using pressure-based transitions
      between Cassie and Wenzel states. During droplet impingement, the effective water
      hammer pressure acting due to the sudden change in the velocity of the droplet is
      determined experimentally and is found to be at least 2 orders of magnitude less
      than values reported in the literature. The experiments show that the water
      hammer pressure depends on the surface morphology and capillary pressure of the
      surface. We propose that the observed reduction in shock pressure may be
      attributed to the presence of air gaps in the substrate. This feature allows
      liquid deformation and hence avoids the sudden stoppage of the droplet motion as
      opposed to droplet behavior on smooth surfaces.

PMID- 22630786
TI  - Phase-rectified signal averaging as a new method for surveillance of growth
      restricted fetuses.
AB  - OBJECTIVE: This study aims to compare average acceleration capacity (AAC), a new
      parameter to assess the dynamic capacity of the fetal autonomous nervous system,
      and short term variation (STV) in fetuses affected by intrauterine growth
      restriction (IUGR) and healthy fetuses. METHODS: A prospective observational
      study was performed, including 39 women with IUGR singleton pregnancies
      (estimated fetal weight <10th percentile and umbilical artery resistance index
      >95th percentile) and 43 healthy control pregnancies matched according to
      gestational age at recording. Ultrasound biometries and Doppler examination were
      performed for identification of IUGR and control fetuses, with subsequent
      analysis of fetal heart rate, resulting in STV and AAC. Follow-up for IUGR and
      control pregnancies was done, with perinatal outcome variables recorded. RESULTS:
      AAC [IUGR mean value 2.0 bpm (interquartile range = 1.6-2.1), control 2.7 bpm
      (2.6-3.0)] differentiates better than STV [IUGR 7.4 ms (5.3-8.9), control 10.9 ms
      (9.2-12.7)] between IUGR and control. The area under the curve for AAC is 97 %
      [95% CI = (0.95-1.0)], for STV 85 % (CI = 0.76-0.93; p < 0.01). Positive
      predictive value for STV is 77% and negative predictive value is 81%. For AAC
      both positive and negative predictive values are 90%. CONCLUSIONS: AAC shows an
      improvement to discriminate between normal and compromised fetuses at a single
      moment in time, in comparison with STV.

PMID- 22630785
TI  - Regulation of mitochondrial permeability transition pore by PINK1.
AB  - BACKGROUND: Loss-of-function mutations in PTEN-induced kinase 1 (PINK1) have been
      linked to familial Parkinson's disease, but the underlying pathogenic mechanism
      remains unclear. We previously reported that loss of PINK1 impairs mitochondrial
      respiratory activity in mouse brains. RESULTS: In this study, we investigate how
      loss of PINK1 impairs mitochondrial respiration using cultured primary
      fibroblasts and neurons. We found that intact mitochondria in PINK1-/- cells
      recapitulate the respiratory defect in isolated mitochondria from PINK1-/- mouse
      brains, suggesting that these PINK1-/- cells are a valid experimental system to
      study the underlying mechanisms. Enzymatic activities of the electron transport
      system complexes are normal in PINK1-/- cells, but mitochondrial transmembrane
      potential is reduced. Interestingly, the opening of the mitochondrial
      permeability transition pore (mPTP) is increased in PINK1-/- cells, and this
      genotypic difference between PINK1-/- and control cells is eliminated by agonists
      or inhibitors of the mPTP. Furthermore, inhibition of mPTP opening rescues the
      defects in transmembrane potential and respiration in PINK1-/- cells. Consistent
      with our earlier findings in mouse brains, mitochondrial morphology is similar
      between PINK1-/- and wild-type cells, indicating that the observed mitochondrial
      functional defects are not due to morphological changes. Following FCCP
      treatment, calcium increases in the cytosol are higher in PINK1-/- compared to
      wild-type cells, suggesting that intra-mitochondrial calcium concentration is
      higher in the absence of PINK1. CONCLUSIONS: Our findings show that loss of PINK1
      causes selective increases in mPTP opening and mitochondrial calcium, and that
      the excessive mPTP opening may underlie the mitochondrial functional defects
      observed in PINK1-/- cells.

PMID- 22630788
TI  - Isolation and identification of metabolites of osthole in rats.
AB  - Osthole (Ost), one of the major components of Cnidium monnieri (L.) Cusson, is
      had the structure of an isopentenoxy-coumarin with a range of pharmacological
      activities. In the present study, the metabolism of Ost in male Sprague-Dawley
      rats was investigated by identifying Ost metabolites excreted in rat urine.
      Following an oral dose of 40 mg/kg Ost, 10 phase I and 3 phase II metabolites
      were isolated from the urine of rats, and their structures identified on the
      basis of a range of spectroscopic data, including 2D-NMR techniques. These
      metabolites were fully characterized as 5'-hydroxyl-osthole (M-1), osthenol (M
      2), 4'-hydroxyl-osthole (M-3), 3, 5'-dihydroxyl-osthole (M-4), 5'-hydroxyl
      osthenol (M-5), 4'-hydroxyl-2', 3'-dihydro-osthenol (M-6), 4'-hydroxyl-osthenol
      (M-7), 3, 4'-dihydroxyl-osthole (M-8), 2', 3'-dihydroxyl-osthole (M-9), 5'
      hydroxyl-2', 3'-dihydroosthole (M-10), osthenol-7-O-beta-D-glucuronide (M-11),
      osthole-4'-O-beta-D-glucuronide (M-12) and osthole-5'-O-beta-D-glycuronate (M
      13). This is the first identification of M-1, M-3 to M-13 in vivo. On the basis
      of the metabolites profile, a possible metabolic pathway for Ost metabolism in
      rats has been proposed. This is the first systematic study on the phases I and II
      metabolites of 8-isopentenoxy-coumarin derivative.

PMID- 22630789
TI  - Editor's corner: editorial in reply to the comments of Griffith Edwards.

PMID- 22630790
TI  - Exploring the ecological association between crime and medical marijuana
      dispensaries.
AB  - OBJECTIVE: Routine activities theory purports that crime occurs in places with a
      suitable target, motivated offender, and lack of guardianship. Medical marijuana
      dispensaries may be places that satisfy these conditions, but this has not yet
      been studied. The current study examined whether the density of medical marijuana
      dispensaries is associated with crime. METHOD: An ecological, cross-sectional
      design was used to explore the spatial relationship between density of medical
      marijuana dispensaries and two types of crime rates (violent crime and property
      crime) in 95 census tracts in Sacramento, CA, during 2009. Spatial error
      regression methods were used to determine associations between crime rates and
      density of medical marijuana dispensaries, controlling for neighborhood
      characteristics associated with routine activities. RESULTS: Violent and property
      crime rates were positively associated with percentage of commercially zoned
      areas, percentage of one-person households, and unemployment rate. Higher violent
      crime rates were associated with concentrated disadvantage. Property crime rates
      were positively associated with the percentage of population 15-24 years of age.
      Density of medical marijuana dispensaries was not associated with violent or
      property crime rates. CONCLUSIONS: Consistent with previous work, variables
      measuring routine activities at the ecological level were related to crime. There
      were no observed cross-sectional associations between the density of medical
      marijuana dispensaries and either violent or property crime rates in this study.
      These results suggest that the density of medical marijuana dispensaries may not
      be associated with crime rates or that other factors, such as measures
      dispensaries take to reduce crime (i.e., doormen, video cameras), may increase
      guardianship such that it deters possible motivated offenders.

PMID- 22630791
TI  - Alcohol use at time of injury and survival following traumatic brain injury:
      results from the National Trauma Data Bank.
AB  - OBJECTIVE: Premised on biological evidence from animal research, recent clinical
      studies have, for the most part, concluded that elevated blood alcohol
      concentration levels are independently associated with higher survival or
      decreased mortality in patients with moderate to severe traumatic brain injury
      (TBI). This study aims to provide some counterevidence to this claim and to
      further future investigations. METHOD: Incident data were drawn from the largest
      U.S. trauma registry, the National Trauma Data Bank, for emergency department
      admission years 2002-2006. TBI was identified according to the National Trauma
      Data Bank's definition using International Classification of Diseases, Ninth
      Revision, Clinical Modification (ICD-9-CM), codes. To eliminate confounding, the
      exact matching method was used to match alcohol-positive with alcohol-negative
      incidents on sex, age, race/ethnicity, and facility. Logistic regression compared
      in-hospital mortality between 44,043 alcohol-positive and 59,817 matched alcohol
      negative TBI incidents, with and without causes and intents of TBI and Injury
      Severity Score as covariates. A sensitivity analysis was performed within a
      subsample of isolated moderate to severe TBI incidents. RESULTS: Alcohol use at
      the time of injury was found to be significantly associated with an increased
      risk for TBI. Including varied causes and intents of TBI and Injury Severity
      Score as potential confounders in the regression model explained away the
      statistical significance of the seemingly protective effect of alcohol against
      TBI mortality for all TBIs and for isolated moderate to severe TBIs. CONCLUSIONS:
      The null finding shows that the purported reduction in TBI mortality attributed
      to positive blood alcohol likely is attributable to residual confounding.
      Accordingly, the risk of TBI associated with alcohol use should not be
      overlooked.

PMID- 22630792
TI  - Associations between adolescent heavy drinking and problem drinking in early
      adulthood: implications for prevention.
AB  - OBJECTIVE: We assessed how heavy episodic drinking (HED) in adolescence (Time 1)
      was related to hazardous drinking as well as symptoms of alcohol problems and
      dependence in early adulthood (Time 2). The key question was to what extent
      preventive measures targeted at underage HED may have a potential to reduce
      problem drinking in early adulthood. METHOD: Data are from the 1992 (Time 1, ages
      14-17 years) and 2005 (Time 2) waves of the Young in Norway Longitudinal Study (N
      = 1,764). In addition to odds ratios and relative risks, we calculated population
      attributable fractions to estimate how the prevalence of hazardous drinking and
      alcohol problems in early adulthood would be affected if adolescent HED at
      various frequencies were eliminated. The results were adjusted for age, gender,
      and measures on impulsivity and delinquency. RESULTS: The risk of problem
      drinking at Time 2 increased with increasing frequency of HED at Time 1, but a
      great deal of discontinuity in drinking behaviors was also observed. The
      population-attributable fractions indicated that if all instances of HED at Time
      1 were eliminated, the expected reduction in hazardous drinking and alcohol
      problems at Time 2 would be 11% and 15%, respectively. CONCLUSIONS: Because of a
      marked discontinuity in drinking behaviors from adolescence to early adulthood,
      the potential long-term effects of interventions targeted at HED among youth are
      likely to be limited.

PMID- 22630793
TI  - Posttraumatic stress disorder symptoms mediate the relationship between traumatic
      experiences and drinking behavior among women attending alcohol-serving venues in
      a South African township.
AB  - OBJECTIVE: South Africa has high rates of traumatic experiences and alcohol abuse
      or dependence, especially among women. Traumatic experiences often result in
      symptoms of posttraumatic stress disorder (PTSD), and PTSD has been associated
      with hazardous drinking. This article examines the relationship between traumatic
      events and hazardous drinking among women who patronized alcohol-serving venues
      in South Africa and examines PTSD as a mediator of this relationship. METHOD: A
      total of 560 women were recruited from a Cape Town township. They completed a
      computerized assessment that included alcohol consumption, history of traumatic
      events, and PTSD symptoms. Mediation analysis examined whether PTSD symptoms
      mediated the relationship between the number of traumatic event categories
      experienced (range: 0-7) and drinking behavior. RESULTS: The mean Alcohol Use
      Disorders Identification Test score in the sample was 12.15 (range: 0-34, SD =
      7.3), with 70.9% reaching criteria for hazardous drinking (AUDIT > 8). The mean
      PTSD score was 36.32 (range: 17-85, SD = 16.3),with 20.9% meeting symptom
      criteria for PTSD (PTSD Checklist with 20.9% meeting symptom criteria for PTSD
      (PTSD Checklist-Civilian Version >= 50). Endorsement of traumatic experiences was
      high, including adult emotional (51.8%), physical (49.6%), and sexual (26.3%)
      abuse; childhood physical (35.0%) and sexual (25.9%) abuse; and other types of
      trauma (83%). All categories of traumatic experiences, except the "other"
      category, were associated with hazardous drinking. PTSD symptoms mediated 46% of
      the relationship between the number of traumatic categories experienced and
      drinking behavior. CONCLUSIONS: Women reported high rates of hazardous drinking
      and high levels of PTSD symptoms, and most had some history of traumatic events.
      There was a strong relationship between traumatic exposure and drinking levels,
      which was largely mediated by PTSD symptoms. Substance use interventions should
      address histories of trauma in this population, where alcohol may be used in part
      to cope with past traumas.

PMID- 22630794
TI  - Interactive effects of childhood maltreatment and recent stressful life events on
      alcohol consumption in adulthood.
AB  - OBJECTIVE: Childhood maltreatment is associated with early alcohol use
      initiation, alcohol-related problem behaviors, and alcohol use disorders in
      adulthood. Heavy drinking risk among individuals exposed to childhood
      maltreatment could be partly attributable to stress sensitization, whereby early
      adversity leads to psychobiological changes that heighten sensitivity to
      subsequent stressors and increase risk for stress-related drinking. We addressed
      this issue by examining whether the association between past-year stressful life
      events and past-year drinking density, a weighted quantity-frequency measure of
      alcohol consumption, was stronger among adults exposed to childhood maltreatment.
      METHOD: Drinking density, stressful life events, and child maltreatment were
      assessed using structured clinical interviews in a sample of 4,038 male and
      female participants ages 20-58 years from the Virginia Adult Twin Study of
      Psychiatric and Substance Use Disorders. Stress sensitization was examined using
      hierarchical multiple regression analyses to test whether stressful events
      moderated the association between maltreatment and drinking density. Analyses
      were stratified by sex and whether the impact was different for independent
      stressful events or dependent stressful events as related to a participant's
      actions. RESULTS: Independent stressful events were associated with heavier
      drinking density among women exposed to maltreatment. In contrast, drinking
      density was roughly the same across independent stressful life events exposure
      among women not exposed to maltreatment. There was little evidence for
      Maltreatment * Independent Stressor interactions in men or Maltreatment *
      Dependent Stressor interactions in either gender. CONCLUSIONS: Early maltreatment
      may have direct effects on vulnerability to stress-related drinking among women,
      particularly in association with stressors that are out of one's control.

PMID- 22630795
TI  - Social adversity, stress, and alcohol problems: Are racial/ethnic minorities and
      the poor more vulnerable?
AB  - OBJECTIVE: Experiences of racial/ethnic bias and unfair treatment are risk
      factors for alcohol problems, and population differences in exposure to these
      social adversities (i.e., differential exposure) may contribute to alcohol
      related disparities. Differential vulnerability is another plausible mechanism
      underlying health disparities, yet few studies have examined whether populations
      differ in their vulnerability to the effects of social adversity on psychological
      stress and the effects of psychological stress on alcohol problems. METHOD: Data
      from the 2005 U.S. National Alcohol Survey (N = 4,080 adult drinkers) were
      analyzed using structural equation modeling to assess an overall model of
      pathways linking social adversity, depressive symptoms, heavy drinking, and
      alcohol dependence. Multiple group analyses were conducted to assess differences
      in the model's relationships among Blacks versus Whites, Hispanics versus Whites,
      and the poor (income below the federal poverty line) versus non-poor (income
      above the poverty line). RESULTS: The overall model explained 48% of the variance
      in alcohol dependence and revealed significant pathways between social adversity
      and alcohol dependence involving depressive symptoms and heavy drinking. The
      effects of social adversity and depressive symptoms were no different among
      Blacks and Hispanics compared with Whites. However, the poor (vs. non-poor)
      showed stronger associations between unfair treatment and depressive symptoms and
      between depressive symptoms and heavy drinking. CONCLUSIONS: Contrary to some
      prior studies, these findings suggest that racial disparities in alcohol problems
      may be more a function of racial/ethnic minorities' greater exposure, rather than
      vulnerability, to chronic stressors such as social adversity. However, observed
      differences between the poor and non-poor imply that differential vulnerability
      contributes to socioeconomic disparities in alcohol problems. Efforts to reduce
      both differential exposure and vulnerability might help to mitigate these
      disparities.

PMID- 22630797
TI  - Daily variations in Spring Break alcohol and sexual behaviors based on
      intentions, perceived norms, and daily trip context.
AB  - OBJECTIVE: Given the known risks of alcohol use and sexual behavior for college
      students on Spring Break, this study was designed to document the behaviors and
      correlates associated with being on a Spring Break trip on a given day
      (controlling for average time on a trip). METHOD: Participants were undergraduate
      students (n = 261; 55% women) who reported that they planned to go on a Spring
      Break trip. Web-based survey responses before and after Spring Break documented
      perceived norms, intentions, and actual behavior on each of the 10 days of Spring
      Break. RESULTS: Students who went on longer trips, who previously engaged in more
      heavy episodic drinking, or who had greater pre-Spring Break intentions to drink
      reported greater alcohol use during Spring Break. Similarly, students with
      greater pre-Spring Break intentions to have sex, greater perceived norms for sex,
      or more previous sexual partners had greater odds of having sex. On days students
      were on trips, they had a greater likelihood of having sex, drinking to higher
      estimated blood alcohol concentrations, consuming more drinks, and reporting
      perceived drunkenness than on nontrip days, especially if they had intentions to
      have sex and drink alcohol (and, for models predicting sexual behavior and
      drunkenness, had greater perceived norms for sex and drinking). CONCLUSIONS:
      Students who went on Spring Break trips engaged in more risk behaviors. In
      addition, the context of being on a trip on a given day was associated with
      increased risk, especially if they had stronger intentions and, in some cases,
      higher perceived norms. Further research is needed to describe the contexts of
      Spring Break trips and how to intervene effectively.

PMID- 22630796
TI  - Alcohol use patterns and trajectories of health-related quality of life in middle
      aged and older adults: a 14-year population-based study.
AB  - OBJECTIVE: A 14-year multiwave panel design was used to examine relationships
      between longitudinal alcohol-consumption patterns, especially persistent moderate
      use, and change in health-related quality of life among middle-aged and older
      adults. METHOD: A nationally representative sample of 5,404 community-dwelling
      Canadians ages 50 and older at baseline (1994/1995) was obtained from the
      longitudinal National Population Health Survey. Alcohol-consumption patterns were
      developed based on the quantity and frequency of use in the 12 months before the
      interview. Health-related quality of life was assessed with the Health Utilities
      Index Mark 3 (HUI3). Latent growth curve modeling was used to estimate the change
      in HUI3 for each alcohol pattern after adjusting for covariates measured at
      baseline. RESULTS: Most participants showed stable alcohol-consumption patterns
      over 6 years. Persistent non-users, persistent former users, those decreasing
      their consumption levels, and those with unstable patterns (i.e., U shaped and
      inverted U shaped) had lower HUI3 scores at baseline compared with persistent
      moderate drinkers. A more rapid decline in HUI3 scores than that observed for
      persistent moderate users was seen only in those with decreasing consumption (p <
      .001). In a subgroup identified as consistently healthy before follow-up,
      longitudinal drinking patterns were associated with initial HUI3 scores but not
      rates of change. CONCLUSIONS: Persistent moderate drinkers had higher initial
      levels of health-related quality of life than persistent nonusers, persistent
      former users, decreasing users, U-shaped users, and inverted U-shaped users.
      However, rates of decline over time were similar for all groups except those
      decreasing their consumption, who had a greater decline in their level of health
      related quality of life than persistent moderate users.

PMID- 22630798
TI  - School bonding as a moderator of the effect of peer influences on alcohol use
      among American Indian adolescents.
AB  - OBJECTIVE: Previous research suggests that substance use among American Indian
      youth is associated with disproportionate rates of morbidity and substance
      misuse. Additional work to understand risk and protective factors for alcohol use
      is needed. The current study examined the role of school bonding in buffering the
      effect of peer alcohol use on a student's own alcohol use among American Indian
      adolescents. METHOD: The present study is part of a larger examination of alcohol
      use among American Indian youth. Survey data were collected from middle and high
      school students during the 2009-2010 and 2010-2011 school years from 37 school
      districts in the United States. The sample consisted of 2,582 students ages 11-19
      years: 1,606 were younger than 16, and 976 were age 16 or older. All students
      self-identified as American Indian or Alaskan Native. The sample was
      approximately equally divided by gender (49% male). RESULTS: For all students,
      peer alcohol use was a risk factor for (a) lifetime alcohol use and (b) level of
      alcohol use among users. School bonding was associated with a lower likelihood of
      lifetime alcohol use for adolescents younger than age 16 and a lower level of use
      among users for all adolescents. School bonding emerged as a protective factor
      that buffers against peer alcohol use among adolescent alcohol users younger than
      16. CONCLUSIONS: Results of the study demonstrate the influence of exposure to
      alcohol-using peers and the protective role of school bonding on alcohol use
      among American Indian adolescents. Implications for prevention are discussed.

PMID- 22630799
TI  - The ties that bind: bonding versus bridging social capital and college student
      party attendance.
AB  - OBJECTIVE: This study explored the relationship between bonding and bridging
      social capital and college student attendance at alcohol-present parties, a
      common method for building informal social networks. METHOD: A random sample of
      students (n = 6,291; 52% female) from a large public midwestern university
      completed a survey regarding their alcohol use and party-related behaviors on
      targeted weekends. The survey also included questions regarding students' living
      arrangements, romantic relationships, and membership in student and community
      organizations. RESULTS: Based on a dichotomous logistic regression analysis, we
      concluded that the act of attending parties largely serves as a complement to,
      rather than a substitute for, more conventional and formal social capital.
      Membership in bonding groups is associated with increased odds of party
      attendance, and bridging exerts no direct effect on party attendance. However,
      bridging capital does mitigate the effect of bonding capital, reducing its
      apparent tendency to promote or contribute to partying. CONCLUSIONS: Off-campus
      parties may offer an informal supplement to more conventional social capital as
      students establish themselves in their new context. These findings may have
      implications for structural decisions (e.g., number of roommates) as well as the
      design of context-based prevention programs that address students' need to
      quickly build social capital without exposing both themselves and the students
      around them to the harms associated with high-risk drinking.

PMID- 22630800
TI  - Daily college student drinking patterns across the first year of college.
AB  - OBJECTIVE: Despite the long recognized importance and well-documented impact of
      drinking patterns on health and safety, college student drinking patterns are
      understudied. This study used a daily-level, academic-year-long, multisite sample
      to identify subpopulations of college student drinking patterns and to describe
      how these groups differ from one another before, during, and after their first
      year of college. METHOD: Two cohorts of first-year college students (n = 588; 59%
      female) reported daily drinking on a biweekly basis using web-based surveys and
      completed surveys before and after their first year of college. RESULTS: Cluster
      analyses based on time series analysis estimates of within-person drinking
      differences (per weekday, semester, first 6 weeks) and other descriptors of day
      to-day drinking identified five drinking patterns: two low (47% and 6%), two
      medium (24% and 15%), and one high (8%) drinking cluster. Multinomial logistic
      regression analyses examined cluster differences in pre-college characteristics
      (i.e., demographics, alcohol outcome expectancies, alcohol problems, depression,
      other substance use) and first-year college experiences (i.e., academic
      engagement, alcohol consequences, risky drinking practices, alcohol problems,
      drinking during academic breaks). Low-drinking students appeared to form a
      relatively homogeneous group, whereas two distinct patterns were found for medium
      drinking students with different weekend and Thursday drinking rates. The
      Thursday drinking cluster showed lower academic engagement and greater
      participation in risky drinking practices. CONCLUSIONS: These findings highlight
      quantitative and qualitative differences in day-to-day drinking patterns and
      suggest a link between motivational differences and drinking patterns, which may
      be addressed in developing tailored interventional strategies.

PMID- 22630801
TI  - Cognitive remediation therapy during treatment for alcohol dependence.
AB  - OBJECTIVE: Cognitive impairments in individuals with alcohol dependence may
      interfere with the progress of treatment and contribute to the progression of the
      disease. This study aimed to determine whether cognitive remediation (CR) therapy
      applied during treatment for alcohol dependence improves cognitive functioning in
      alcohol-dependent inpatients. A secondary aim was to evaluate whether the
      benefits of CR generalize to noncognitive clinically meaningful outcomes at the
      end of inpatient treatment. METHOD: Forty-one alcohol-dependent patients entering
      inpatient treatment for alcohol dependence were randomly assigned to receive
      conventional treatment (n = 21) or an additional 12 sessions of computer-assisted
      CR focusing on cognitive enhancement in attention/executive function and memory
      domains (n = 20). Assessments of cognitive abilities in these domains as well as
      of psychological well-being and alcohol craving were conducted at baseline (at
      the beginning of inpatient treatment) and after CR (at the end of treatment).
      RESULTS: Results indicated that, relative to patients completing conventional
      treatment, those who received supplemental CR showed significant improvement in
      attention/executive function and memory domains, particularly in attention
      (alertness, divided attention), working memory, and delayed memory (recall). In
      addition, patients receiving CR during alcohol-dependence treatment showed
      significantly greater improvements in psychological well-being (Symptom Checklist
      90-Revised) and in the compulsion aspect of craving (Obsessive Compulsive
      Drinking Scale-German version). CONCLUSIONS: CR during inpatient treatment for
      alcohol dependence is effective in improving cognitive impairments in alcohol
      dependent patients. The benefits generalize to noncognitive outcomes,
      demonstrating that CR may be an efficacious adjunctive intervention for the
      treatment of alcohol dependence.

PMID- 22630802
TI  - Who seeks care where? Utilization of mental health and substance use disorder
      treatment in two national samples of individuals with alcohol use disorders.
AB  - OBJECTIVE: Only a fraction of individuals with alcohol use disorders (AUDs)
      receive any AUD treatment during a given year. If a substantial proportion of
      individuals with unmet need for AUD treatment are receiving mental health
      treatment, accessibility of AUD treatment could potentially be improved by
      implementing strategies to ensure that individuals receiving mental health care
      are referred to the AUD sector or by increasing rates of AUD treatment in
      individuals receiving mental health treatment. METHOD: We assessed patterns and
      predictors of mental health treatment and AUD treatment among individuals with 12
      month AUDs, using secondary data analyses from two national surveys, the National
      Survey on Drug Use and Health (NSDUH; n = 4,545 individuals with AUDs) and the
      National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; n =
      3,327 individuals with AUDs). RESULTS: In both NSDUH and NESARC, 8% of
      individuals with AUDs reported past-year AUD treatment. Among individuals with
      AUDs, mental health treatment was more common than AUD treatment, with 20% of
      NSDUH respondents and 11% of NESARC respondents reporting receiving mental health
      treatment. Greater mental health morbidity increased the odds of mental health
      treatment, and AUD severity increased the odds of AUD treatment. Mental health
      morbidity also increased the odds of AUD treatment, mainly by increasing the odds
      of receiving the category of both AUD and mental health treatment. CONCLUSIONS:
      Because individuals with AUDs are more likely to receive mental health treatment
      than AUD treatment, a key opportunity to improve the overall accessibility of
      treatment for AUDs may be to focus on improving AUD treatment among individuals
      receiving mental health treatment.

PMID- 22630804
TI  - Relationships between local enforcement, alcohol availability, drinking norms,
      and adolescent alcohol use in 50 California cities.
AB  - OBJECTIVE: This study investigated relationships between local alcohol policies,
      enforcement, alcohol outlet density, adult alcohol use, and underage drinking in
      50 California cities. METHOD: Eight local alcohol policies (e.g., conditional use
      permit, social host ordinance, window/billboard advertising) were rated for each
      city based on their comprehensiveness. Local alcohol enforcement was based on
      grants received from the California Alcoholic Beverage Control agency for
      enforcement of underage drinking laws. Outlet density was based on the number of
      on- and off-premise outlets per roadway mile. Level of adult alcohol use was
      ascertained from a survey of 8,553 adults and underage drinking (frequency of
      past-year alcohol use and heavy drinking) from surveys of 1,312 adolescents in
      2009 and 2010. Multilevel regression analyses were conducted to examine the
      effects of policies, enforcement, and other community-level variables on
      adolescent drinking, controlling for youth demographic characteristics. Mediating
      effects of adolescents' perceived ease of obtaining alcohol, perceived
      enforcement, and perceived acceptability of alcohol use also were examined.
      RESULTS: None of the eight local alcohol-policy ratings were associated with
      adolescent drinking. Funding for underage drinking enforcement activities was
      inversely related to frequency of past-year alcohol use, whereas outlet density
      and adult drinking were positively related to both past-year alcohol use and
      heavy drinking. These relationships were attenuated when controlling for
      perceived ease of obtaining alcohol, enforcement, and acceptability of alcohol
      use, providing evidence formediation. CONCLUSIONS: Adolescent alcohol use and
      heavy drinking appear to be influenced by enforcement of underage drinking laws,
      alcohol outlet density, and adult alcohol use. These community-level influences
      may be at least partially mediated through adolescents' perceptions of alcohol
      availability, acceptability of alcohol use, and perceived likelihood of getting
      in trouble with local police.

PMID- 22630803
TI  - Factors associated with first utilization of different types of care for alcohol
      problems.
AB  - OBJECTIVE: The purpose of this research was to investigate whether factors
      associated with first obtaining care for alcohol problems vary by source of care.
      METHOD: This study used data from the National Epidemiologic Survey on Alcohol
      and Related Conditions to examine initiation of different types of care over a 3
      year follow-up interval among individuals with baseline alcohol use disorders who
      had not previously obtained any care (n = 2,170). Three hierarchical, mutually
      exclusive types of care were compared: substance use disorder (SUD) specialty
      sources, general medical but no SUD specialty sources, and nonmedical sources
      only. RESULTS: Having injured oneself or someone else because of drinking was
      associated with initiating all three types of care. Additional factors associated
      with initiating care from SUD specialty treatment sources (vs. no care) comprised
      male sex, alcohol use disorder severity, major financial problems, and
      nondependent tobacco/drug use. Factors associated with initiating care from
      general medical but not SUD specialty sources (vs. no care) comprised
      marriage/cohabitation, college student status, number of medical conditions, and
      other substance dependence. Factors associated with obtaining care only from
      nonmedical sources (vs. no care) comprised low income and anxiety disorder. When
      direct comparisons were made among types of care, factors drawing individuals
      into general medical care for reasons not necessarily related to alcohol problems
      were those that primarily distinguished utilization of general medical sources
      from the other two types of care. CONCLUSIONS: Results support the importance of
      screening in general medical practice and student health services as an important
      means of identifying individuals in need of brief intervention or more intensive
      SUD treatment and reiterate the importance of nonmedical sources for individuals
      whose alcohol problems might never be addressed in routine medical visits.

PMID- 22630805
TI  - "To believe or not to believe?" Religiosity, spirituality, and alcohol use among
      Hungarian adolescents.
AB  - OBJECTIVE: A growing number of studies focus on the relationship between
      religiosity/spirituality and substance use, including drinking. Although these
      studies often find a negative association between religiosity and adolescent
      alcohol use, different religious variables may play an altering role in alcohol
      related activities. The primary goal of the present study was to examine the
      relationship between a set of religious variables (religious denomination, church
      membership, religious attendance, praying, religiosity, spiritual beliefs, and
      well-being) and drinking patterns (current alcohol use, lifetime prevalence of
      drinking, and heavy episodic drinking) among a sample of Hungarian youth. METHOD:
      Data were collected among high school students (N = 592; ages between 14 and 17
      years; 48.1% male) from a randomly selected set of schools in Szeged, Hungary,
      using a self-administered questionnaire and standardized procedures. Student
      participation was voluntary and confidential. RESULTS: Despite a high level of
      alcohol use and a relatively low level of religiosity in the sample, we detected
      a relationship between the importance of religiousness/religious well-being and
      alcohol use, although religious denomination and affiliation were not significant
      correlates. Religious attendance and private praying were associated with lower
      odds of alcohol use among girls; boys who reported a belief in traditional
      religion were less likely to engage in alcohol use. CONCLUSIONS: These
      exploratory results provide further details to a growing body of research showing
      that despite adolescents' low religious involvement, religiosity can play an
      important role in some youth's lives and may serve as a protective factor against
      alcohol use and misuse.

PMID- 22630806
TI  - Do substance use norms and perceived drug availability mediate sexual orientation
      differences in patterns of substance use? Results from the California Quality of
      Life Survey II.
AB  - OBJECTIVE: Illicit drug and heavy alcohol use is more common among sexual
      minorities compared with heterosexuals. This difference has sometimes been
      attributed to more tolerant substance use norms within the gay community,
      although evidence is sparse. The current study investigated the role of perceived
      drug availability and tolerant injunctive norms in mediating the linkage between
      minority sexual orientation status and higher rates of prior-year substance use.
      METHOD: We used data from the second California Quality of Life Survey (Cal-QOL
      II), a followback telephone survey in 2008-2009 of individuals first interviewed
      in the population-based 2007 California Health Interview Survey. The sample
      comprised 2,671 individuals, oversampled for minority sexual orientation.
      Respondents were administered a structured interview assessing past-year alcohol
      and illicit drug use, perceptions of perceived illicit drug availability, and
      injunctive norms concerning illicit drug and heavier alcohol use. We used
      structural equation modeling methods to test a mediational model linking sexual
      orientation and substance use behaviors via perceptions of drug availability and
      social norms pertaining to substance use. RESULTS: Compared with heterosexual
      individuals, sexual minorities reported higher levels of substance use, perceived
      drug availability, and tolerant social norms. A successfully fitting model
      suggests that much of the association between minority sexual orientation and
      substance use is mediated by these sexual orientation-related differences in drug
      availability perceptions and tolerant norms for substance use. CONCLUSIONS:
      Social environmental context, including subcultural norms and perceived drug
      availability, is an important factor influencing substance use among sexual
      minorities and should be addressed in community interventions.

PMID- 22630808
TI  - "The evil genius of the habit": DSM-5 seen in historical context.

PMID- 22630807
TI  - Effects of interactive voice response self-monitoring on natural resolution of
      drinking problems: utilization and behavioral economic factors.
AB  - OBJECTIVE: Most problem drinkers do not seek help, and many recover on their own.
      A randomized controlled trial evaluated whether supportive interactive voice
      response (IVR) self-monitoring facilitated such "natural" resolutions. Based on
      behavioral economics, effects on drinking outcomes were hypothesized to vary with
      drinkers' baseline "time horizons," reflecting preferences among commodities of
      different value available over different delays and with their IVR utilization.
      METHOD: Recently resolved untreated problem drinkers were randomized to a 24-week
      IVR self-monitoring program (n = 87) or an assessment-only control condition (n =
      98). Baseline interviews assessed outcome predictors including behavioral
      economic measures of reward preferences (delay discounting, pre-resolution
      monetary allocation to alcohol vs. savings). Six-month outcomes were categorized
      as resolved abstinent, resolved nonabstinent, unresolved, or missing. Complier
      average causal effect (CACE) models examined IVR self-monitoring effects.
      RESULTS: IVR self-monitoring compliers (>=70% scheduled calls completed) were
      older and had greater pre-resolution drinking control and lower discounting than
      noncompliers (<70%). A CACE model interaction showed that observed compliers in
      the IVR group with shorter time horizons (expressed by greater pre-resolution
      spending on alcohol than savings) were more likely to attain moderation than
      abstinent resolutions compared with predicted compliers in the control group with
      shorter time horizons and with all noncompliers. Intention-to-treat analytical
      models revealed no IVR-related effects. More balanced spending on savings versus
      alcohol predicted moderation in both approaches. CONCLUSIONS: IVR interventions
      should consider factors affecting IVR utilization and drinking outcomes,
      including person-specific behavioral economic variables. CACE models provide
      tools to evaluate interventions involving extended participation.

PMID- 22630809
TI  - Combining abuse and dependence in DSM-5.

PMID- 22630810
TI  - Rationale for changes in DSM-5.

PMID- 22630811
TI  - "Bath salt"-induced agitated paranoia: a case series.

PMID- 22630812
TI  - Systematic review and meta-analysis of the effect of equine assisted activities
      and therapies on gross motor outcome in children with cerebral palsy.
AB  - PURPOSE: To evaluate the literature on the efficacy of equine assisted activities
      and therapies (EAAT) on gross motor outcomes representing the ICF component of
      body functions and activity in children with cerebral palsy (CP). METHODS: We
      conducted a systematic review and meta-analysis of randomized controlled trials
      and observational studies of hippotherapy (HPOT) and therapeutic horseback riding
      (TR) for children with spastic CP. Gross motor outcomes, assessed via muscle
      activity and muscle tone, gait, posture and Gross Motor Function Measures (GMFM)
      were evaluated. RESULTS: Five TR studies and nine HPOT studies were included. Our
      meta-analysis indicated that short-term HPOT (total riding time 8-10 min)
      significantly reduced asymmetrical activity of the hip adductor muscles. HPOT
      could improve postural control in children with spastic CP, GMFCS level < 5.
      However, the evidence did not show a statistically significant effect on GMFM
      after long-term HPOT or TR (total riding time, 8-22 h) in children with spastic
      CP. CONCLUSIONS: This systematic review found insufficient evidence to support
      the claim that long-term TR or HPOT provide a significant benefit to children
      with spastic CP. We found no statistically significant evidence of either
      therapeutic effect or maintenance effects on the gross motor activity status in
      CP children.

PMID- 22630813
TI  - In response to "supratrochlear artery island paramedian forehead flap for
      reconstructing the exenterated patient".

PMID- 22630814
TI  - Human complement C3 is a substrate for transglutaminases. A functional link
      between non-protease-based members of the coagulation and complement cascades.
AB  - In this study, we report the finding of functional cross-talk between two non
      protease components of the complement and coagulation cascades. We show that
      complement C3, a central component of the complement system, is associated with
      the fibrin clot and that C3 becomes covalently cross-linked to other proteins
      during coagulation. Enzymatic incorporation of dansylcadaverine and dansyl
      PGGQQIV into C3 by coagulation factor XIIIa and tissue transglutaminase
      demonstrated that C3 is a transglutaminase substrate. This suggested that
      coagulation factor XIIIa covalently cross-links C3 to clot components during
      coagulation. Using mass spectrometry, we verified that C3 indeed is covalently
      associated with the fibrin clot in a ratio of 0.05:1 relative to the known
      coagulation factor XIIIa substrate alpha2-antiplasmin.

PMID- 22630815
TI  - Availability of information relating to high quality research.

PMID- 22630816
TI  - Reversible copper(II)/(I) electrochemical potential switching driven by visible
      light-induced coordinated ring rotation.
AB  - We here describe the first metal complex system in which electronic signals can
      be repeatedly extracted by converting bistable states related to an
      intramolecular ligand rotational motion, which is fueled by visible light. The
      molecular structure for relating an electron transfer and a motion consists of a
      copper center and a coordinated unsymmetrically substituted pyrimidine
      derivative, whose rotational isomerization causes an electrochemical potential
      shift. To harness light energy effectively through metal-to-ligand charge
      transfer (MLCT) excitation, we prepared a simple copper(I) complex coordinated by
      a 4-methyl-2-(6'-methyl-2'-pyridyl)pyrimidine and a bulky diimine. The
      thermodynamic and kinetic parameters of redox and rotational reactions were
      analyzed by cyclic voltammograms at variable temperatures, by considering four
      stable isomers related to copper(II)/(I) states and rotational isomeric states.
      The key feature of this compound is that the rotation is frozen in the copper(I)
      state (rate constant for the rotation, k(Ii->o) = 10(-4) s(-1)) but is active in
      the copper(II) state (k(IIi->o) = 10(-1) s(-1)) at 203 K. The compound makes a
      bypass route to the isomeric metastable copper(I) state, via a tentative
      copper(II) state formed by photoelectron transfer (PET) in the presence of a
      redox mediator, decamethylferrocenium ion (DMFc(+)), or upon a partial oxidation
      of the complex. Light- and heat-driven rotation in the copper(I) state with a
      potential shift (DeltaE degrees ' = 0.14 V) was analyzed by electrochemical
      measurements of the complex in the solution state. The rotor could be reset to
      the initial state by heating, thereby completing the cycle and enabling repeated
      operation fueled by light energy. A significant redox potential shift associated
      with the copper(II)/(I) transition accompanied the rotation, thereby providing a
      new type of molecular signaling system.

PMID- 22630817
TI  - What is preventable harm in healthcare? A systematic review of definitions.
AB  - BACKGROUND: Mitigating or reducing the risk of harm associated with the delivery
      of healthcare is a policy priority. While the risk of harm can be reduced in some
      instances (i.e. preventable), what constitutes preventable harm remains unclear.
      A standardized and clear definition of preventable harm is the first step towards
      safer and more efficient healthcare delivery system. We aimed to summarize the
      definitions of preventable harm and its conceptualization in healthcare. METHODS:
      We conducted a comprehensive electronic search of relevant databases from January
      2001 to June 2011 for publications that reported a definition of preventable
      harm. Only English language publications were included. Definitions were coded
      for common concepts and themes. We included any study type, both original studies
      and reviews. Two reviewers screened the references for eligibility and 28%
      (127/460) were finally included. Data collected from studies included study type,
      description of the study population and setting, and data corresponding to the
      outcome of interest. Three reviewers extracted the data. The level of agreement
      between the reviewers was calculated. RESULTS: One hundred and twenty seven
      studies were eligible. The three most prevalent preventable harms in the included
      studies were: medication adverse events (33/127 studies, 26%), central line
      infections (7/127, 6%) and venous thromboembolism (5/127, 4%). Seven themes or
      definitions for preventable harm were encountered. The top three were: presence
      of an identifiable modifiable cause (58/132 definitions, 44%), reasonable
      adaptation to a process will prevent future recurrence (30/132, 23%), adherence
      to guidelines (22/132, 16%). Data on the validity or operational characteristic
      (e.g., accuracy, reproducibility) of definitions were limited. CONCLUSIONS: There
      is limited empirical evidence of the validity and reliability of the available
      definitions of preventable harm, such that no single one is supported by high
      quality evidence. The most common definition is "presence of an identifiable,
      modifiable cause of harm".

PMID- 22630818
TI  - The mean platelet volume and atherogenic index of plasma in nondipper
      normotensive individuals compared to dippers.
AB  - Mean platelet volume (MPV) is a determinant of platelet activation. Atherogenic
      index of plasma (AIP), which is defined as the logarithm of the ratio of plasma
      level of triglycerides to the level of high-density lipoprotein (HDL)-cholesterol
      (log[ TG/HDL-C]), has recently been used as a marker of atherogenicity. This
      study included 104 normotensive individuals. Mean platelet volume and AIP were
      measured in all patients. Nondipper individuals (8.6 +/- 0.9 fL, 0.3 +/- 0.2)
      demonstrated higher values of MPV and AIP compared with dippers (7.9 +/- 1.1 fL,
      0.1 +/- 0.2) (P < .001 and < .001, respectively). Mean platelet volume and AIP
      have a positive correlation with insufficient decline in nocturnal blood
      pressure.

PMID- 22630820
TI  - Herbal cocktail as anti-infective: promising therapeutic for the treatment of
      viral diseases.
AB  - Herbal products have gained considerable interest among the pharmaceutical
      companies and consumers due to the minimal side effects associated with them. The
      bioflavanoids present in these products are the key players in modulating their
      effects. Several therapeutic effects have been attributed to the bioflavanoids
      present in green tea and turmeric. Antimicrobial activity is one among the
      spectrum of activities they exhibit. Curcumin and catechins, the principle
      components of turmeric and green tea respectively have virucidal and virustatic
      actions. An antimicrobial composition consisting of extracts from green tea and
      turmeric have shown to be highly potent against various microbes, especially
      viruses. In the present review, we have discussed the patents and the antiviral
      effects of curcumin and catechins. The antimalarial effect of curcumin has also
      been discussed.

PMID- 22630819
TI  - Infliximab modifies mesenteric adipose tissue alterations and intestinal
      inflammation in rats with TNBS-induced colitis.
AB  - OBJECTIVE: Infliximab is a monoclonal anti-TNF-alpha antibody that is used
      therapeutically to treat Crohn's disease (CD). High levels of pro-inflammatory
      cytokines, especially TNF-alpha, have been observed in the gastrointestinal tract
      of CD patients and were associated with alterations in the mesenteric adipose
      tissue, which also contributed to the high levels of adipokine release. The
      authors used a rat model of colitis that produces mesenteric adipose tissue
      alterations that are associated with intestinal inflammation to study the effects
      that infliximab treatment has on adipokine production, morphological alterations
      in adipose tissue and intestinal inflammation. MATERIAL AND METHODS: The ability
      of infliximab to neutralize rat TNF-alpha was evaluated in vitro using U937
      cells. Colitis was induced by repeated intracolonic trinitrobenzene sulfonic acid
      instillations and was evaluated by macroscopic score, histopathological analysis,
      myeloperoxidase activity, TNF-alpha and IL-10 expression as well as iNOS
      (inducible NO synthase) expression and JNK phosphorylation in colon samples. The
      alterations in adipose tissue were assessed by TNF-alpha, IL-10, leptin,
      adiponectin and resistin levels as well as adipocyte size and peroxisome
      proliferator-activated receptor (PPAR)-gamma expression. RESULTS: Infliximab
      treatment controlled intestinal inflammation, which reduced lesions and
      neutrophil infiltration. Inflammatory markers, such as iNOS expression and JNK
      phosphorylation, were also reduced. In mesenteric adipose tissue, infliximab
      increased the production of IL-10 and resistin, which was associated with the
      restoration of adipocyte morphology and PPAR-gamma expression. CONCLUSIONS: Our
      results suggest that infliximab could contribute to the control of intestinal
      inflammation by modifying adipokine production by mesenteric adipose tissue.

PMID- 22630821
TI  - Potential applications of antimicrobial fatty acids in medicine, agriculture and
      other industries.
AB  - The antimicrobial effects of free fatty acids are well recognised and these
      compounds can prevent the growth of or directly kill bacteria, fungi and other
      microbes by affecting multiple cellular targets, including the cell membrane and
      components found therein. Moreover, fatty acids exert detrimental effects on
      microbial pathogens by interfering with mechanisms of virulence, such as
      preventing biofilm formation and inhibiting the production of toxins and enzymes.
      The antimicrobial properties of free fatty acids can be exploited for the
      preservation of perishable products, such as food and cosmetics, and for the
      prevention and treatment of infections. These safe natural products are
      particularly useful in circumstances where antimicrobial activity is required but
      where the use of conventional antibiotics is undesirable or forbidden. This
      review focuses on the most promising prospects for exploiting the antimicrobial
      properties of free fatty acids for applications in various industries. The
      benefits of using fatty acids as antimicrobial agents are discussed and relevant
      recent patents are highlighted.

PMID- 22630823
TI  - Biological Macromolecular Dynamics.

PMID- 22630822
TI  - Present and future of tyrosine kinase inhibitors in renal cell carcinoma:
      analysis of hematologic toxicity.
AB  - Tyrosine kinase inhibitors (TKIs) have dramatically improved the outcome of renal
      cell carcinoma (RCC) patients. The use of these agents requires early and
      appropriate management of side effects such as hematologic adverse events (HAE),
      in order to avoid unnecessary dose reductions and transitory or definitive
      treatment discontinuations. Beyond the increased infective risk, myelosuppression
      contributes to TKI-related fatigue, thus reducing both patients' quality of life
      and overall survival (OS). However, the frequency and severity of
      myelosuppression vary among sunitinib, sorafenib, pazopanib and axitinib, based
      on their different kinase selectivity. Their activity against fms-related
      tyrosine kinase 3 (FLT3 or CD135) and c-kit, which are essential for survival and
      differentiation of hemopoietic progenitor cells, is critical to determine the
      hematologic toxicity profiles. This review describes the molecular mechanisms
      underlying the TKI effects exerted on hematopoiesis and immune response and
      related recent patents, of drugs already approved or still under evaluation in
      RCC, highlighting the potential impact of these effects on tumor response to
      treatment.

PMID- 22630826
TI  - Accurate tracking genetic markers in haemophilia linkage analysis: a matter
      beyond scientific priority.

PMID- 22630827
TI  - In vitro indications for favourable non-additive effects on ruminal methane
      mitigation between high-phenolic and high-quality forages.
AB  - Feeding plants containing elevated levels of polyphenols may reduce ruminal CH4
      emissions, but at the expense of nutrient utilisation. There might, however, be
      non-additive effects when combining high-phenolic plants with well-digestible,
      high-nutrient feeds. To test whether non-additive effects exist, the leaves of
      Carica papaya (high in dietary quality, low in polyphenols), Clidemia hirta (high
      in hydrolysable tannins), Swietenia mahagoni (high in condensed tannins) and
      Eugenia aquea (high in non-tannin phenolics) were tested alone and in all
      possible mixtures (n 15 treatments). An amount of 200 mg DM of samples was
      incubated in vitro (24 h; 39 degrees C) with buffered rumen fluid using the
      Hohenheim gas test apparatus. After the incubation, total gas production, CH4
      concentration and fermentation profiles were determined. The levels of absolute
      CH4, and CH4:SCFA and CH4:total gas ratios were lower (P< 0.05) when incubating a
      combination of C. papaya and any high-phenolic plants (C. hirta, S. mahagoni and
      E. aquea) than when incubating C. papaya alone. Additionally, mixtures resulted
      in non-additive effects for all CH4-related parameters of the order of 2-15 %
      deviation from the expected value (P< 0.01). This means that, by combining these
      plants, CH4 in relation to the fermentative capacity was lower than that
      predicted when assuming the linearity of the effects. Similar non-additive
      effects of combining C. papaya with the other plants were found for NH3
      concentrations but not for SCFA concentrations. In conclusion, using mixtures of
      high-quality plants and high-phenolic plants could be one approach to CH4
      mitigation; however, this awaits in vivo confirmation.

PMID- 22630828
TI  - Response to: 'Meanderings into the regulation of effector class by the immune
      system: derivation of the trauma model' by Melvin Cohn.
AB  - Cohn M. Meanderings into the regulation of effector class by the immune system:
      derivation of the trauma model. Scand J Immunol 2012;76:77-88 delves into the
      discussion of how the immune system might regulate the decision between the
      immune response effector classes, and in particular identifies some key questions
      that need to be asked to understand how different classes of immune response
      occurring at the same time might be able to remain coherent and discrete. This is
      a needed discussion that advances the field, and the experiments proposed will go
      a long way to increasing our understanding of effector class regulation. However,
      in my opinion, the author makes some strong statements requiring substantiation
      regarding the impossibility of the involvement of germline-selected recognitive
      events as participating in self/non-self discrimination. Furthermore, the present
      discussion ignores a large body of contemporary literature describing the
      function and specificity of FoxP3+ regulatory T cells (T(reg) ) and formulates a
      theory that specifically excludes a role for T(reg)  in maintaining self
      tolerance without placing the contemporary evidence in the context of that
      theory. Thus in my opinion, these shortcomings should be addressed by the author.

PMID- 22630829
TI  - Interaction of the European genotype porcine reproductive and respiratory
      syndrome virus (PRRSV) with sialoadhesin (CD169/Siglec-1) inhibits alveolar
      macrophage phagocytosis.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus
      that shows a restricted in vivo tropism for subsets of porcine macrophages, with
      alveolar macrophages being major target cells. The virus is associated with
      respiratory problems in pigs of all ages and is commonly isolated on farms with
      porcine respiratory disease complex (PRDC). Due to virus-induced macrophage death
      early in infection, PRRSV hampers the innate defence against pathogens in the
      lungs. In addition, the virus might also directly affect the antimicrobial
      functions of macrophages. This study examined whether interaction of European
      genotype PRRSV with primary alveolar macrophages (PAM) affects their phagocytic
      capacity. Inoculation of macrophages with both subtype I PRRSV (LV) and subtype
      III PRRSV (Lena) showed that the virus inhibits PAM phagocytosis. Similar results
      were obtained using inactivated PRRSV (LV), showing that initial interaction of
      the virion with the cell is sufficient to reduce phagocytosis, and that no
      productive infection is required. When macrophages were incubated with
      sialoadhesin- (Sn) or CD163-specific antibodies, two entry mediators of the
      virus, only Sn-specific antibodies downregulated the phagocytic capacity of PAM,
      indicating that interaction with Sn, but not CD163, mediates the inhibitory
      effect of PRRSV on phagocytosis. In conclusion, this study shows that European
      genotype PRRSV inhibits PAM phagocytosis in vitro, through the interaction with
      its internalization receptor Sn. If similar events occur in vivo, this
      interaction may be important in the development of PRDC, as often seen in the
      field.

PMID- 22630830
TI  - Accumulation of tilianin and rosmarinic acid and expression of phenylpropanoid
      biosynthetic genes in Agastache rugosa.
AB  - Korean mint (Agastache rugosa), a perennial, medicinal plant of the Labiatae
      family, has many useful constituents, including monoterpenes and
      phenylpropanoids. Among these, tilianin and rosmarinic acid, 2 well-known natural
      products, have many pharmacologically useful properties. Chalcone synthase (CHS)
      and chalcone isomerase (CHI) catalyze the first and second committed steps in the
      phenylpropanoid pathway of plants, leading to the production of tilianin. In this
      study, cDNAs encoding CHS (ArCHS) and CHI (ArCHI) were isolated from A. rugosa
      using rapid amplification of cDNA ends (RACE)-PCR. Amino acid sequence alignments
      showed that ArCHS and ArCHI shared high sequence identity and active sites with
      their respective orthologous genes. Quantitative real-time PCR analysis was used
      to determine the expression levels of genes involved in tilianin and rosmarinic
      acid biosyntheses in the flowers, leaves, stems, and roots of A. rugosa. High
      performance liquid chromatography (HPLC) revealed that the accumulation pattern
      of tilianin matched the expression patterns of ArCHS and ArCHI in different
      organs of A. rugosa. Moreover, acacetin, the precursor of tilianin, also
      demonstrated an accumulation pattern congruent with the expression of these 2
      genes. The transcription levels of ArPAL, ArC4H, and Ar4CL were the highest in
      the leaves or flowers of the plant, which also contained a relatively high amount
      of rosmarinic acid. However, the roots showed a significant content of rosmarinic
      acid, although the transcription of ArPAL, ArC4H, and Ar4CL were low. The
      findings of our study support the medicinal usefulness of A. rugosa and indicate
      targets for increasing tilianin and rosmarinic acid production in this plant. 

PMID- 22630831
TI  - Integration of clinical and imaging data to predict death in hemodialysis
      patients.
AB  - In a prior publication, we demonstrated that a model integrating clinical and
      simple imaging data predicted the presence and severity of coronary artery
      calcification in prevalent hemodialysis patients. Herein we report the ability of
      the same model to predict all-cause death. We assessed all-cause mortality in 141
      consecutive maintenance hemodialysis patients from two dialysis centers followed
      for a median of 79 months from enrollment. Patients were risk stratified
      according to a simple cardiovascular calcification index (CCI) that included
      patient's age, dialysis vintage, calcification of the cardiac valves, and
      abdominal aorta. The mean patients' age was 55 +/- 14 years. Abdominal aorta
      calcification was present in 57% of the patients, and 44% and 38% had aortic and
      mitral valve calcification, respectively. During follow-up, 75 deaths (93 deaths
      per 1000 person-years) were recorded. The CCI was linearly associated with risk
      of death, such that the unadjusted hazard risk (HR) increased by 12% for each
      point increase in CCI (P < 0.001). Further adjustments for age, sex, study
      center, diabetes mellitus, history of cardiovascular disease, hypertension,
      congestive heart failure, left ventricular hypertrophy, systolic, and diastolic
      blood pressure did not substantially change the strength of this association (HR
      1.10; 95%CI: 1.00-1.21; P = 0.03). The CCI is a simple clinical model that can be
      used to risk stratify maintenance hemodialysis patients.

PMID- 22630832
TI  - Temperature influence on 4-aminophthalimide emission in 1-chloroalkanes plus
      water mixtures.
AB  - Thermochromic emission shifts of 4-aminophthalimide (4-AP) dissolved in three 1
      chloroalkanes, namely, 1-chloropropane, 1-chlorobutane, and 1-chlorohexane,
      together with fluorescence decays measured at different wavelengths, all solvents
      containing different small amounts of water (10(-4)-10(-2) M), are reported in a
      broad temperature range covering the bulk water melting point. Our studies have
      shown that 4-AP is an effective indicator of water presence even at
      concentrations given by solvent suppliers for so-called "dry" solvents.
      Additionally, indications of water ice-clusters formation in 1-chloroalkanes,
      starting at different temperatures depending on water concentration, have been
      found. Finally, 4-AP in 1-chloroalkane + water mixture is shown to present at
      different temperatures three basic types of sources of time-resolved emission
      spectra (TRES) time/spectral evolution: emission of two kinetically coupled
      species, solvent relaxation, and simultaneous emission of two independent
      species.

PMID- 22631029
TI  - The early bird gets the shrimp: confronting assumptions of isotopic equilibrium
      and homogeneity in a wild bird population.
AB  - 1. Because stable isotope distributions in organic material vary systematically
      across energy gradients that exist in ecosystems, community and population
      structures, and in individual physiological systems, isotope values in animal
      tissues have helped address a broad range of questions in animal ecology. It
      follows that every tissue sample provides an isotopic profile that can be used to
      study dietary or movement histories of individual animals. Interpretations of
      these profiles depend on the assumption that metabolic pools are isotopically
      well mixed and in equilibrium with dietary resources prior to tissue synthesis,
      and they extend to the population level by assuming isotope profiles are
      identically distributed for animals using the same proximal dietary resource. As
      these assumptions are never fully met, studying structure in the variance of
      tissue isotope values from wild populations is informative. 2. We studied
      variation in delta(13) C, delta(15) N, delta(2) H and delta(18) O data for
      feathers from a population of eared grebes (Podiceps nigricollis) that migrate to
      Great Salt Lake each fall to moult feathers. During this time, they cannot fly
      and feed almost exclusively on superabundant brine shrimp (Artemia franciscana).
      The ecological simplicity of this situation minimized the usual spatial and
      trophic complexities often present in natural studies of feather isotope values.
      3. Ranges and variances of isotope values for the feathers were larger than those
      from previously published studies that report feather isotopic variance, but they
      were bimodally distributed in all isotope dimensions. Isotope values for proximal
      dietary resources and local surface water show that some of the feathers we
      assumed to have been grown locally must have been grown before birds reached
      isotopic equilibrium with local diet or immediately prior to arrival at Great
      Salt Lake. 4. Our study provides novel insights about resource use strategies in
      eared grebes during migration. More generally, it demonstrates the utility of
      studying variance structures and questioning assumptions implicit in the
      interpretation of stable isotope data from wild animals.

PMID- 22631030
TI  - Addiction and rehabilitation in autobiographical books by rock artists, 1974
      2010.
AB  - INTRODUCTION AND AIMS: This paper explores excessive appetites, addiction and
      rehabilitation as described in the autobiographies, memoirs and diaries of rock
      artists. DESIGN AND METHODS: The data collection focused on autobiographical rock
      books written in English by internationally recognised rock artists before 2011.
      In total, 96 autobiographical books were published between 1974 and 2010. The
      mean age of the authors was 50 years and 17% of the books were by female authors.
      Data were encoded for: (i) addiction; (ii) the object of addiction; (iii)
      personal addiction; (iv) rehabilitation; (v) personal rehabilitation; and (vi)
      the type of recovery from the addiction. RESULTS: Of the books, 82% described
      addiction, 62% personal addiction, 57% rehabilitation and 40% personal
      participation in rehabilitation. The most common addictions were alcoholism,
      opiate addiction and cocaine addiction. Addicted rock stars described addictions
      differently from non-addicts. Of addicted rock artists, 51% recovered with the
      help of rehabilitation, 42% self-recovered and 7% continued the excess. There has
      been an increase in the prevalence of addiction in autobiographical rock books
      over time. In addition, it was found that gender affected the type of recovery.
      DISCUSSION AND CONCLUSIONS: Autobiographical books by rock artists have been
      published in increasing numbers in the last two decades. The artists in question
      have described their personal experiences of addiction and rehabilitation and
      discussed the problems related to alcohol, drugs and excessive behaviour. The
      books do not glamorise addiction or excessive lifestyles. Rather, they indicate
      that attitudes towards drugs and alcohol are changing in the rock business.

PMID- 22631031
TI  - Ligand field effect at oxide-metal interface on the chemical reactivity of
      ultrathin oxide film surface.
AB  - Ultrathin oxide film is currently one of the paramount candidates for a
      heterogeneous catalyst because it provides an additional dimension, i.e., film
      thickness, to control chemical reactivity. Here, we demonstrate that the chemical
      reactivity of ultrathin MgO film grown on Ag(100) substrate for the dissociation
      of individual water molecules can be systematically controlled by interface
      dopants over the film thickness. Density functional theory calculations revealed
      that adhesion at the oxide-metal interface can be addressed by the ligand field
      effect and is linearly correlated with the chemical reactivity of the oxide film.
      In addition, our results indicate that the concentration of dopant at the
      interface can be controlled by tuning the drawing effect of oxide film. Our study
      provides not only profound insight into chemical reactivity control of ultrathin
      oxide film supported by a metal substrate but also an impetus for investigating
      ultrathin oxide films for a wider range of applications.

PMID- 22631032
TI  - Evaluation of the pharmacodynamics of acetylsalicylic acid 81 mg with or without
      esomeprazole 20 mg in healthy volunteers.
AB  - BACKGROUND: The absence of a pharmacokinetic interaction between the proton pump
      inhibitor esomeprazole (40 mg) and acetylsalicylic acid (aspirin, ASA; 325 mg)
      has previously been established. OBJECTIVE: This study set out to investigate the
      potential for pharmacodynamic interaction between low-dose ASA and esomeprazole
      in healthy volunteers, by measuring ASA antiplatelet activity. STUDY DESIGN: This
      was a single-center, open-label, two-period, randomized crossover study.
      PARTICIPANTS: Healthy male and female volunteers aged 18-75 years were included.
      All volunteers received ASA 81 mg once daily for 5 days prior to the study (pre
      screen). Subjects were eligible for inclusion if they had aspirin reactivity
      units (ARU, as measured by the VerifyNow ASA assay) of <550 on Day 6.
      INTERVENTION: After pre-screening and a washout period of at least 14 days,
      eligible volunteers received ASA 81 mg with or without esomeprazole 20 mg once
      daily for 5 days in randomized order, with a 14-day washout between treatments.
      MAIN OUTCOME MEASURE: The main outcome measure was the antiplatelet activity of
      ASA, as assessed by ARU ratio relative to baseline in the VerifyNow ASA assay;
      suppression of serum thromboxane B(2) (TXB(2)) was a secondary endpoint.
      Statistical comparisons were made using linear mixed models. RESULTS: A total of
      29 volunteers (19 aged >=50 years; 8 women; 21 men) were evaluable for
      pharmacodynamic analysis (per protocol). All volunteers on both treatments
      achieved ARU <550 at Day 6. The geometric mean ratio of Day 6 to Day 1 (baseline)
      platelet aggregation was 0.70 (95% confidence interval [CI] 0.68, 0.72) with ASA
      alone and 0.71 (95% CI 0.69, 0.74) with ASA + esomeprazole. The ratio of platelet
      aggregation (ASA + esomeprazole/ASA) was 1.02 (95% CI 0.99, 1.05). ASA
      administered alone or with esomeprazole reduced serum TXB(2) by more than 99.5%.
      The ratio of suppression of serum TXB(2) levels (ASA + esomeprazole/ASA) was 1.06
      (95% CI 0.88, 1.29). The combination of ASA and esomeprazole was well tolerated.
      CONCLUSION: No pharmacodynamic interaction between low-dose ASA and esomeprazole
      was found with regard to platelet function. TRIAL REGISTRATION: Registered at
      ClinicalTrials. gov as NCT01199328.

PMID- 22631033
TI  - Reward expectancy promotes generalized increases in attentional bias for
      rewarding stimuli.
AB  - Expectations of drug availability increase the magnitude of attentional biases
      for drug-related cues. However, it is unknown whether these effects are outcome
      specific, or whether expectation of a specific reinforcer produces a general
      enhancement of attentional bias for other types of rewarding cues. In the present
      study, 31 social drinkers completed an eye-tracking task in which attentional
      bias for alcohol- and chocolate-related cues was assessed while the expectation
      of receiving alcohol and chocolate was manipulated on a trial-by-trial basis.
      Participants showed attentional bias for alcohol and chocolate cues (relative to
      neutral cues) overall. Importantly, these attentional biases for reward cues were
      magnified when participants expected to receive alcohol and chocolate, but
      effects were not outcome specific: The expectation of receiving either alcohol or
      chocolate increased attentional bias for both alcohol and chocolate cues. Results
      suggest that anticipation of reward produces a general rather than an outcome
      specific enhancement of attentional bias for reward-related stimuli.

PMID- 22631034
TI  - Recent advances and treatment challenges in patients with non-transfusion
      dependent thalassemia.

PMID- 22631035
TI  - The role of ineffective erythropoiesis in non-transfusion-dependent thalassemia.
AB  - Ineffective erythropoiesis is the hallmark of beta-thalassemia that triggers a
      cascade of compensatory mechanisms resulting in clinical sequelae such as
      erythroid marrow expansion, extramedullary hematopoiesis, splenomegaly, and
      increased gastrointestinal iron absorption. Recent studies have begun to shed
      light on the complex molecular mechanisms underlying ineffective erythropoiesis
      and the associated compensatory pathways; this new understanding may lead to the
      development of novel therapies. Increased or excessive activation of the
      Jak2/STAT5 pathway promotes unnecessary disproportionate proliferation of
      erythroid progenitors, while other factors suppress serum hepcidin levels leading
      to dysregulation of iron metabolism. Preclinical studies suggest that Jak
      inhibitors, hepcidin agonists, and exogenous transferrin may help to restore
      normal erythropoiesis and iron metabolism and reduce splenomegaly; however,
      further research is needed.

PMID- 22631036
TI  - Iron overload in non-transfusion-dependent thalassemia: a clinical perspective.
AB  - Iron overload due to increased intestinal iron absorption represents an important
      clinical problem in patients with non-transfusion-dependent thalassemia (NTDT),
      particularly as they advance in age. Current models for iron metabolism in
      patients with beta (beta)-thalassemia intermedia (TI) suggest that suppression of
      serum hepcidin results in increased iron absorption and release of iron from the
      reticuloendothelial system, leading to depletion of macrophage iron, relatively
      low levels of serum ferritin, and liver iron loading. The clinical consequences
      of iron overload in patients with NTDT are multifactorial and include
      endocrinopathy, bone disease, thromboembolism, pulmonary hypertension,
      cerebrovascular and neuronal damage, liver fibrosis or cirrhosis, and increased
      risk of hepatocellular carcinoma. Although serum ferritin levels correlate with
      liver iron concentration (LIC), they underestimate iron load in these patients
      compared with transfusion-dependent patients with equivalent LIC. Therefore,
      direct measurement of LIC is recommended with chelation therapy as indicated.

PMID- 22631037
TI  - Hypercoagulability in non-transfusion-dependent thalassemia.
AB  - Beta (beta)-thalassemia is characterized by a hypercoagulable state and an
      increased risk of thrombosis, which can result in significant morbidity and
      mortality. The molecular and cellular mechanisms contributing to
      hypercoagulability are diverse and include chronic platelet activation,
      alteration of red blood cell membranes, abnormal expression of adhesion molecules
      on vascular endothelial cells, and dysregulation of hemostasis. Regular
      transfusions decrease the risk of thrombosis, whereas splenectomy significantly
      increases the risk. Splenectomized adults with non-transfusion-dependent
      thalassemia are also at high risk for ischemic brain damage. Strategies to lower
      the risk of thrombosis should be considered, including transfusion therapy to
      raise hemoglobin levels and avoidance or delay of splenectomy.

PMID- 22631038
TI  - Contemporary approaches to treatment of beta-thalassemia intermedia.
AB  - Beta-thalassemia intermedia (TI) is associated with a variety of serious clinical
      complications that require proactive and comprehensive management. These include
      skeletal deformities and osteopenia, compensatory extramedullary hematopoiesis
      and tumor formation, progressive splenomegaly, a hypercoagulable state resulting
      in thromboembolic events and pulmonary hypertension, and increased
      gastrointestinal iron absorption that often results in nontransfusional iron
      overload and liver damage. Although TI is generally considered a non-transfusion
      dependent thalassemia, transfusion therapy may be an important part of the
      comprehensive management of this disease. This review describes the current state
      of the art for medical management of TI, with particular focus on the roles of
      splenectomy, transfusion, and iron chelation therapy.

PMID- 22631039
TI  - Treatment strategies for hemoglobin E beta-thalassemia.
AB  - Hemoglobin E beta (beta)-thalassemia (HbE thalassemia) is a very common form of
      beta-thalassemia that exhibits a heterogeneous clinical presentation and variable
      clinical course. The reasons for this extraordinary clinical heterogeneity are
      not completely understood. A number of factors, both genetic and environmental,
      appear to modify the severity of HbE thalassemia. There is also an emerging
      understanding that the HbE thalassemia phenotype may be unstable, which may
      reflect changes in adaptation to anemia and, possibly, attenuation of the
      erythropoietin response over time. These factors make it difficult to develop
      broad treatment guidelines. It is now generally appreciated that steady-state
      hemoglobin concentration may be of limited value to determine which patients need
      regular transfusions. Therefore, periodic reassessment of the need for
      transfusion therapy is recommended, and intermittent transfusion therapy may now
      be explored as an approach in this disorder.

PMID- 22631040
TI  - The definition and epidemiology of non-transfusion-dependent thalassemia.
AB  - Inherited hemoglobin-related disorders, which include the structural variants
      (hemoglobin S, C, and E) and the alpha (alpha)- and beta (beta)-thalassemias,
      affect more than 300,000 children annually, particularly in malaria-endemic
      regions stretching from sub-Saharan Africa and the Mediterranean to Southeast
      Asia. Screening for carriers of these traits is important to provide prenatal
      genetic counseling and to accurately estimate the true prevalence and public
      health burden of these disorders. The clinical course of thalassemias, which
      affect nearly 70,000 children annually, is highly variable depending on the
      mixture of inherited alleles. The primary forms of non-transfusion-dependent
      thalassemia include beta-thalassemia intermedia, hemoglobin E beta-thalassemia,
      and hemoglobin H disease. Early clinical recognition of these disorders is
      essential to prevent affected children from being mistakenly placed on life-long
      transfusion therapy.

PMID- 22631041
TI  - Advances in the treatment of alpha-thalassemia.
AB  - Alpha (alpha)-thalassemia represents a group of recessively inherited hemoglobin
      disorders marked by deficient or absent synthesis of 1 to all 4 of the alpha
      globin genes. Inactivation of 3 alpha-globin genes--either by deletional or
      nondeletional mutations--results in hemoglobin H (Hb H) disease. Patients with Hb
      H disease produce hemoglobin composed of all beta chains and have moderate to
      severe hemolytic anemia, a variable degree of ineffective erythropoiesis, and
      splenomegaly. Transfusion requirements vary depending on the mutation and
      clinical severity. Treatment for deletional Hb H disease is primarily
      preventative and transfusions are uncommon. Patients with nondeletional Hb H
      disease (e.g., Hb H Constant Spring) typically have more severe anemia, and
      approximately one-third require regular transfusions. These patients often
      require comprehensive, multidisciplinary care. This chapter focuses on screening,
      diagnosis, and treatment approaches for patients with Hb H disease.

PMID- 22631042
TI  - The emerging role of fetal hemoglobin induction in non-transfusion-dependent
      thalassemia.
AB  - Patients with beta (beta)-thalassemia who have high levels of fetal hemoglobin
      (HbF) have less severe anemia and are often transfusion-independent. Therefore,
      augmentation of HbF production has been a longstanding therapeutic objective.
      Three classes of HbF-inducing agents have been investigated for the treatment of
      beta-thalassemia including chemotherapeutics, short-chain fatty acid derivatives,
      and recombinant erythropoietin. These agents have several different mechanisms of
      action and have been shown to increase total hemoglobin levels by 1-5 g/dL above
      baseline, but none has been able to sustain the therapeutic levels needed to
      maintain transfusion independence. Recent findings have provided new insights
      regarding HbF regulatory pathways, providing new opportunities for derepression
      of fetal globin gene expression and HbF induction.

PMID- 22631043
TI  - Recent advances in the molecular understanding of non-transfusion-dependent
      thalassemia.
AB  - Thalassemias are a group of inherited autosomal recessive hematologic disorders
      that occur because of defects in the alpha (alpha)- and beta (beta)-globin genes
      of adult hemoglobin (Hb). An imbalance in the synthesis of one or more of the
      globin chains can result in a wide spectrum of phenotypes depending on the type
      and amount of globin synthesized and additional genetic modifiers. In patients
      with thalassemia intermedia, a condition known as non-transfusion-dependent
      thalassemia (NTDT), transfusion requirements are absent or episodic. Non
      transfusion-dependent thalassemia includes beta-thalassemia intermedia, HbE beta
      thalassemia, and alpha-thalassemia intermedia, also known as Hb H disease. This
      article focuses on the molecular features and genetic mutations specific to NTDT.

PMID- 22631044
TI  - Antenatal dexamethasone has no adverse effects on child physical and cognitive
      development: a long-term cohort follow-up investigation.
AB  - OBJECTIVE: Antenatal corticosteroids are extensively given in pregnancies with
      threatened preterm labour as a prophylactic method to reduce some kinds of
      neonatal diseases. Dexamethasone is one kind of commonly used corticosteroid, but
      controversies still remain whether it leads to adverse effects on neonatal long
      term development or not. The purpose of this study was to investigate the
      influence of prenatal exposure to one or two dosages of dexamethasone on neonatal
      physical and cognitive development of children at 1, 3 and 6 years of age.
      METHODS: This was a retrospective cohort study. The body length, head
      circumference and body weight were measured in every infant and child to evaluate
      physical development. The mental development index (MDI) and a psychomotor
      development index (PDI) were used to evaluate mental and cognitive development in
      children of ages 1 year and 3 years while verbal intelligence quotient (VIQ) and
      performance intelligence quotient (PIQ) scores were used to evaluate mental and
      cognitive development in children of age of 6 years. There were 1554 infants at 1
      year, 1328 children at 3 years and 1297 preschool children at 6 years followed.
      RESULTS: There were no significant differences between antenatal dexamethasone
      exposure groups and antenatal dexamethasone non-exposure groups on physical
      development index and MDI, PDI, VIQ and PIQ. CONCLUSIONS: The results of this
      investigation suggested that one or two dosages of antenatal dexamethasone is
      safe for the use of inevitable preterm birth.

PMID- 22631045
TI  - The bodily experience of apraxia in everyday activities: a phenomenological
      study.
AB  - PURPOSE: The aim of this study is to explore apraxia as a phenomenon in everyday
      activities, as experienced by a group of stroke patients. Some consequences for
      clinical practice are suggested. METHOD: In this phenomenological hermeneutical
      study, six persons with apraxia were followed from 2 to 6 months, from the early
      phase of stroke rehabilitation. ADL-situations and interactions with therapists
      were observed and videotaped repeatedly during the rehabilitation trajectory, to
      provide access to and familiarity with the participant's apractic difficulties
      over time. Two in-depth interviews were conducted with each participant.
      Interviews and video observations were analyzed together, taking Merleau-Ponty's
      concept of bodily intentionality as basis for analysis and his phenomenology as
      the main theoretical perspective of the study. RESULTS: Five types of altered
      bodily intentionality were described by the participants [ 1 ]: Gap between
      intention and bodily action [ 2 ], Fragmented awareness in action [ 3 ], Peculiar
      actions and odd bodies [ 4 ], Intentionality on the loose, and [ 5 ] Fighting
      against tools. These were recognized as characteristics typical of the apraxia
      experience. CONCLUSION: The phenomenology of Merleau-Ponty, and his concept of
      bodily intentionality in particular, elucidate the way specific apractic
      difficulties come into being and may thus render apraxia less incomprehensible.
      The apraxia phenomenon appears as characteristic fragmentations of anticipation
      inherent in action performance, thereby "slackening" the bodily intentionality.
      Identifying apractic changes of intentionality may help health professionals to
      adjust and individualize therapy, and facilitate patients' acting competence in
      everyday life.

PMID- 22631046
TI  - True reference nanosensor realized with silicon nanowires.
AB  - Conventional gate oxide layers (e.g., SiO(2), Al(2)O(3), or HfO(2)) in silicon
      field-effect transistors (FETs) provide highly active surfaces, which can be
      exploited for electronic pH sensing. Recently, great progress has been achieved
      in pH sensing using compact integrateable nanowire FETs. However, it has turned
      out to be much harder to realize a true reference electrode, which--while sensing
      the electrostatic potential--does not respond to the proton concentration. In
      this work, we demonstrate a highly effective reference sensor, a so-called
      reference FET, whose proton sensitivity is suppressed by as much as 2 orders of
      magnitude. To do so, the Al(2)O(3) surface of a nanowire FET was passivated with
      a self-assembled monolayer of silanes with a long alkyl chain. We have found that
      a full passivation can be achieved only after an extended period of self
      assembling lasting several days at 80  degrees C. We use this slow process to
      measure the number of active proton binding sites as a function of time by a
      quantitative comparison of the measured nonlinear pH-sensitivities to a
      theoretical model (site-binding model). Furthermore, we have found that a
      partially passivated surface can sense small changes in the number of active
      binding sites reaching a detection limit of deltaN(s) ~ 170 MUm(-2) Hz(-1/2) at
      10 Hz and pH 3.

PMID- 22631047
TI  - Levator aponeurosis sandwich flap for reconstruction of upper eyelid defect.
AB  - A 72-year-old woman suffered from a sebaceous gland carcinoma on her left upper
      eyelid. The tumour was 13 * 5 mm without metastasis. The tumour was excised with
      a 5-mm safety margin, resulting in a large, full-thickness defect in which almost
      all of the tarsal plate, approximately half of the orbicularis oculi muscle, and
      part of the levator aponeurosis were lost. Reconstruction of the upper eyelid was
      successfully performed with a levator aponeurosis sandwich flap, upon which the
      posterior lamella was covered by a free tarsal graft with medial and lateral
      periosteal flaps, and a skin graft from the contralateral upper eyelid for the
      anterior lamella. No lagophthalmos was demonstrated after the operation. Six
      months postoperatively, there was no tumour recurrence, no ocular complications,
      and good cosmetic results.

PMID- 22631048
TI  - Structural Insights into retinal guanylylcyclase-GCAP-2 interaction determined by
      cross-linking and mass spectrometry.
AB  - The retinal guanylylcyclases ROS-GC 1 and 2 are regulated via the intracellular
      site by guanylylcyclase-activating proteins (GCAPs). The mechanisms of how GCAPs
      activate their target proteins remain elusive as exclusively structures of
      nonactivating calcium-bound GCAP-1 and -2 are available. In this work, we apply a
      combination of chemical cross-linking with amine-reactive cross-linkers and
      photoaffinity labeling followed by a mass spectrometric analysis of the created
      cross-linked products to study the interaction between N-terminally myristoylated
      GCAP-2 and a peptide derived from the catalytic domain of full-length ROS-GC 1.
      In our studies, only a few cross-linked products were obtained for calcium-bound
      GCAP-2, pointing to a well-defined structure of the GCAP-2-GC peptide complex. A
      much larger number of cross-links were detected in the absence of calcium,
      indicating a high flexibility of calcium-free GCAP-2 in the complex with the GC
      peptide. On the basis of the distance constraints imposed by the cross-links, we
      were able to create a structural model of the calcium-loaded complex between
      myristoylated GCAP-2 and the GC peptide.

PMID- 22631049
TI  - Change in high-sensitive cardiac troponin T on hypertensive treatment.
AB  - The aim of this study was to compare the differences in the levels of a highly
      sensitive cardiac troponin T (Hs-cTnT) between Losartan (LOS) plus
      hydrochlorothiazide (HCTZ) and amlodipine. Seventy-eight hypertensive patients
      were randomized to receive LOS/HCTZ or amlodipine for 8 weeks. Both treatments
      decreased clinic and 24-hour blood pressure to the same extent. The Hs-cTnT level
      was significantly reduced in the amlodipine group (P < .05), but such a reduction
      was not found in the LOS/HCTZ group in the upper half group of Hs-cTnT level at
      baseline. Amlodipine had a more beneficial effect than LOS/HCTZ in patients with
      high Hs-cTnT levels.

PMID- 22631051
TI  - Intermittent manually controlled versus continuous infusion of propofol for deep
      sedation during interventional endoscopy: a prospective randomized trial.
AB  - INTRODUCTION: Beside the traditional, intermittent bolus application of propofol,
      continuous propofol infusion via infusion pump is an alternative procedure for
      deep sedation during long-lasting interventional endoscopy. However, up to now,
      there are no randomized comparisons for gastrointestinal endoscopy. METHODS: One
      hundred patients (ERCP: n = 60, EUS: n = 40) were randomly assigned to receive
      intermittent bolus application ("bolus group") or continuous infusion ("perfusor
      group") of propofol sedation after induction with 3 mg midazolam for deep
      sedation. Patients in the bolus group received an initial propofol dose according
      to body weight (bw <70 kg: 40 mg; bw >= 70 kg 60 mg). In the perfusor group, bw
      adapted, continuous propofol infusion (6 mg/kg) via the Injectomat 2000 MC
      (Fresenius-Kabi) was administered after an initial bolus of 1 mg/kg. Vital signs,
      dose of propofol, patient cooperation (VAS 1-10), sedation depth, and the
      recovery time as well as the quality of recovery were evaluated. RESULTS: Total
      propofol dose in the bolus group 305 +/- 155 mg (100-570 mg) and in the perfusor
      group 343 +/- 123 mg (126-590 mg, p = 0.5) were comparable. Oxygen saturation
      below 90% was seen in four patients of each group, with no need for assisted
      ventilation. Arterial blood pressure <90 mmHg was documented in two patients in
      the bolus group and seven patients in the perfusor group (p = 0.16). Patients'
      cooperation was rated as good in both groups (bolus group, 9.1 +/- 0.9; perfusor
      group, 8.9 +/- 1; p = 0.17). Recovery time was significantly shorter in the bolus
      group compared with the perfusor group (19 +/- 5 versus 23 +/- 6 min, p < 0.001)
      whereas the quality of recovery was nearly identical in both groups. CONCLUSION:
      Both sedation regimens allow nearly identical good controllability of propofol
      sedation. However, recovery time was significantly slower and hypotension was
      tended to occur more often in the perfusor group.

PMID- 22631050
TI  - Effect of vitamin D on aortic remodeling in streptozotocin-induced diabetes.
AB  - BACKGROUND: Diabetes mellitus is associated with micro- and macrovascular
      complications and increased cardiovascular risk. Elevated levels of serum
      asymmetric dimethylarginine (ADMA) may be responsible for endothelial dysfunction
      associated with diabetes-induced vascular impairment. Vitamin D may have
      potential protective effects against arterial stiffening. This study aimed to
      examine both the effects of diabetes on the functional/structural properties of
      the aorta and the endothelial function and the effects of vitamin D
      supplementation. METHODS: Male Wistar rats (n = 30) were randomly assigned to
      control untreated, diabetic untreated, and diabetic + cholecalciferol groups.
      Diabetes was induced by intraperitoneal injection of streptozotocin, followed by
      oral administration of cholecalciferol (500 IU/kg) for 10 weeks in the treatment
      group. Aortic pulse wave velocity (PWV) was recorded over a mean arterial
      pressure (MAP) range of 50 to 200 mmHg using a dual pressure sensor catheter.
      Intravenous infusion of phenylephrine and nitroglycerine was used to increase and
      decrease MAP, respectively. Serum 25-hydroxyvitamin D [25(OH)D] levels were
      measured using a radioimmune assay. ADMA levels in serum were measured by enzyme
      linked immunoassay. Aortic samples were collected for histomorphometrical
      analysis. RESULTS: PWV up to MAP 170 mmHg did not reveal any significant
      differences between all groups, but in diabetic rats, PWV was significantly
      elevated across MAP range between 170 and 200 mmHg. Isobaric PWV was similar
      between the treated and untreated diabetic groups, despite significant
      differences in the levels of serum 25(OH)D (493 +/- 125 nmol/L vs 108 +/- 38
      nmol/L, respectively). Serum levels of ADMA were similarly increased in the
      treated and untreated diabetic groups, compared to the control group. The
      concentration and integrity of the elastic lamellae in the medial layer of the
      aorta was impaired in untreated diabetic rats and improved by vitamin D
      supplementation. CONCLUSION: PWV profile determined under isobaric conditions
      demonstrated differential effects of uncontrolled diabetes on aortic stiffness.
      Diabetes was also associated with elevated serum levels of ADMA. Vitamin D
      supplementation did not improve the functional indices of aortic stiffness or
      endothelial function, but prevented the fragmentation of elastic fibers in the
      aortic media.

PMID- 22631052
TI  - Assembly of aptamer switch probes and photosensitizer on gold nanorods for
      targeted photothermal and photodynamic cancer therapy.
AB  - An aptamer switch probe (ASP) linking chlorin e6 (Ce6), a photosensitizer
      molecule, to the surface of gold nanorods (AuNRs) was used to target cancer cells
      for photodynamic therapy (PDT) and photothermal therapy (PTT). In the presence of
      target cancer cells, the ASP changes conformation to drive Ce6 away from the gold
      surface, thereby producing singlet oxygen for PDT upon light irradiation. Since
      each AuNR is modified with many ASP-Ce6 molecules, the AuNR-ASP-Ce6 conjugate
      yields enhanced binding and therapeutic effect by the added ability to carry many
      photosensitizers. In addition, absorption of radiation by the gold nanorods
      enables further cell destruction by the photothermal effect. Consequently, this
      multimodal AuNR-ASP-Ce6 conjugate offers a remarkably improved and synergistic
      therapeutic effect compared to PTT or PDT alone, providing high specificity and
      therapeutic efficiency, which can be generalized to other types of cancer
      therapies.

PMID- 22631054
TI  - Future immunosuppression in organ transplantation: treating the innate immune
      system of the deceased donor--start tomorrow.
AB  - This article, based in part on an invited talk at the Annual International
      Conference of Saudi Society of Nephrology & Transplantation in 2012, reviews
      current notions of the emerging field of innate alloimmunity by highlighting
      novel thoughts regarding future immunosuppressive therapy in organ
      transplantation. In light of new insights into the mechanisms of innate immunity
      on one hand and the essential role of regulatory T cells in controlling
      alloimmune responses on the other hand, potential clinical tools to generate
      tolerogenic dendritic cells are explored. These cells have been shown to promote
      induction of regulatory T cells that possess the potential to prevent acute and
      chronic allograft rejection. Experimental findings from both research areas are
      discussed in support of the notion that presentation of alloantigens under
      subimmunogenic noninflammatory conditions, achieved by vigorous inhibition of
      oxidative injury-induced allograft inflammation (known to occur in both the
      deceased donor and the recipient during allograft reperfusion), may lead to the
      induction of tolerogenic dendritic cell-mediated regulatory T cells, thereby
      offering a realistic opportunity to induce allotolerance in transplant
      recipients. However, before planning clinical trials in recipients, the start of
      such a novel therapeutic strategy to prevent allograft rejection could consist of
      designing and performing a quadruple drug treatment of deceased (brain-dead)
      donors aimed at generating donor-derived tolerogenic dendritic cells. The
      combination use of (1) an antioxidant, (2) a complement-inhibiting agent, (3) an
      IL-1beta inhibitor, and (4) a polyclonal antilymphocytic preparation is
      recommended as the preferred choice of such a donor treatment. If proven
      successful in organ donors, similar therapeutic modalities should subsequently be
      considered to apply to the recipient during allograft reperfusion under strict
      study conditions.

PMID- 22631053
TI  - Trade-offs between drug toxicity and benefit in the multi-antibiotic resistance
      system underlie optimal growth of E. coli.
AB  - BACKGROUND: Efflux is a widespread mechanism of reversible drug resistance in
      bacteria that can be triggered by environmental stressors, including many classes
      of drugs. While such chemicals when used alone are typically toxic to the cell,
      they can also induce the efflux of a broad range of agents and may therefore
      prove beneficial to cells in the presence of multiple stressors. The cellular
      response to a combination of such chemical stressors may be governed by a trade
      off between the fitness costs due to drug toxicity and benefits mediated by
      inducible systems. Unfortunately, disentangling the cost-benefit interplay using
      measurements of bacterial growth in response to the competing effects of the
      drugs is not possible without the support of a theoretical framework. RESULTS:
      Here, we use the well-studied multiple antibiotic resistance (MAR) system in E.
      coli to experimentally characterize the trade-off between drug toxicity ("cost")
      and drug-induced resistance ("benefit") mediated by efflux pumps. Specifically,
      we show that the combined effects of a MAR-inducing drug and an antibiotic are
      governed by a superposition of cost and benefit functions that govern these trade
      offs. We find that this superposition holds for all drug concentrations, and it
      therefore allows us to describe the full dose-response diagram for a drug pair
      using simpler cost and benefit functions. Moreover, this framework predicts the
      existence of optimal growth at a non-trivial concentration of inducer. We
      demonstrate that optimal growth does not coincide with maximum induction of the
      mar promoter, but instead results from the interplay between drug toxicity and
      mar induction. Finally, we derived and experimentally validated a general phase
      diagram highlighting the role of these opposing effects in shaping the
      interaction between two drugs. CONCLUSIONS: Our analysis provides a quantitative
      description of the MAR system and highlights the trade-off between inducible
      resistance and the toxicity of the inducing agent in a multi-component
      environment. The results provide a predictive framework for the combined effects
      of drug toxicity and induction of the MAR system that are usually masked by bulk
      measurements of bacterial growth. The framework may also be useful for
      identifying optimal growth conditions in more general systems where combinations
      of environmental cues contribute to both transient resistance and toxicity.

PMID- 22631055
TI  - Current concepts in histocompatibility during heart transplant.
AB  - Sensitized candidates for heart transplant usually end up on a long waiting list
      and have an increased risk of rejection, graft loss, and incidence of cardiac
      allograft vasculopathy. An increasing number of studies have demonstrated the
      negative effect of preformed and posttransplant antibodies on graft survival.
      Thus, in sensitized patients, the combination of new, appropriate,
      desensitization protocols, and monitoring of posttransplant development of donor
      specific antibodies may improve short-term and long-term outcomes. Introduction
      of more-sensitive and more-specific techniques for antibody detection provides a
      valid tool for assessing the degree of pretransplant HLA histocompatibility, and,
      therefore, predicting the results of crossmatch in sensitized patients, which are
      difficult to transplant. Currently, there are no accurate and standard methods to
      determine the functional characteristics of antibodies detected by solid-phase
      assay and, therefore, to predict their clinical relevance. Therefore, the future
      of heart transplantation requires a better understanding of tissue typing
      techniques and the effect of anti-HLA antibodies on clinical outcome to prevent
      discrimination against sensitized patients at the time of organ allocation.

PMID- 22631056
TI  - A snapshot of renal transplant patients using medical web browsing.
AB  - OBJECTIVES: This study explored the pattern of Internet use by renal transplant
      patients in the West of Scotland. MATERIALS AND METHODS: A 31-item questionnaire
      was used to obtain information about patient's Internet use and the relations
      between Internet use and sex, age, education, and health requirements. RESULTS:
      The study consists of 84 postrenal transplant patient surveys. Validation of the
      questionnaire showed an intraclass correlation coefficient 0.77 to 0.96 with 95%
      confidence interval (CI 0.75-0.99). The overall response rate was 65% (n=84/130).
      In all, 87% of the patients (n=73/84) had access to a computer and the Internet.
      And 94% of the patients (n=60/64) in age groups 21 to 60 years had access to the
      Internet with no difference in the access in various age subgroups, whereas 67%
      of the patients (n=12/18) in age group 61 to 70 years (P = .004) had Internet
      access. The Internet was a preferred source of health information for 70% of the
      patients (n=59/84) as compared to books 17% (n=14/84; P = .003) and magazines 12%
      (n=10/84; P = .001). Of the Internet group, 90% (n=53/59) looked up information
      on transplantation mostly about transplant operations (69%) and rejection (66%).
      Of all the patients, 85% (n=71/84) of them would like the transplant team to
      develop a Web site for information on transplantation and 52 (62%) would like to
      receive health advice by e-mail. CONCLUSIONS: The majority of renal transplant
      patients use the Internet for information on transplantation. Almost all patients
      under 60 years old had access to the Internet for this purpose; suggesting a
      trend toward the Internet as the favored way to get information. Transplant units
      should develop flexible, Web-based sources of transplant-related information.
      This would allow rapid adaptation to changes in prevalent practice, reflecting
      the preferences of the patient population.

PMID- 22631057
TI  - Adverse reactions of immunosuppressive drugs in Iranian adult kidney transplant
      recipients.
AB  - OBJECTIVES: To evaluate the pattern of immunosuppressive drug adverse reactions
      in adult kidney transplant recipients in Iran. MATERIALS AND METHODS: Adult
      kidney transplant outpatients under immunosuppressive therapy were recruited into
      the study. All adverse drug reactions to immunosuppressants and their relevant
      clinical and paraclinical characteristics were recorded. Causality assessment was
      performed by the Naranjo algorithm. The seriousness of adverse drug reactions was
      determined by the World Health Organization definition. The Schumock and Thornton
      questionnaire was used to assess the preventability of adverse drug reactions.
      Statistical analyses were performed. RESULTS: A total of 1100 adverse drug
      reactions were detected from 120 kidney transplant recipients. Increased appetite
      (9.09%) was the adverse reaction reported most frequently. Causality assessment
      revealed that 1019 adverse drug reactions (92.64%) were possible. Forty adverse
      drug reactions (3.64%) were identified as serious. Six hundred seventy-one
      adverse drug reactions (61%) were preventable. Posttransplant duration was
      significantly correlated with the number of adverse drug reactions (R=0.19; P =
      .035). CONCLUSIONS: All renal allograft recipients experienced at least 1
      immunosuppressant-related adverse reaction. Prolongation of immunosuppressive
      treatment resulted in an increase in adverse drug reactions.

PMID- 22631058
TI  - Early allograft biopsies performed during delayed graft function may not be
      necessary under thymoglobulin induction.
AB  - OBJECTIVES: Delayed graft function affects up to 50% of kidney transplant
      recipients. Some guidelines recommend surveillance biopsies beginning 7 days
      after engraftment. This may be unnecessary with anti-thymocyte globulin
      induction. MATERIALS AND METHODS: We conducted a retrospective study of deceased
      donor renal transplant recipients with delayed graft function. RESULTS: One
      hundred eleven patients met the inclusion criteria. The incidence of rejections
      during delayed graft function was 2.7%. They were diagnosed between 9 and 11 days
      after transplant. The subsequent incidence of rejection at 12-month follow-up was
      13.5% (n=15). The median time to rejection after transplant was 10 weeks.
      Fourteen of 15 patients had subtherapeutic immunosuppression. The only risk
      factor associated with later rejection after delayed graft function was use of
      donors after cardiac death. CONCLUSIONS: Early rejection during delayed graft
      function with anti-thymocyte globulin induction and maintenance immunosuppression
      with tacrolimus, mycophenolate mofetil, and steroids is rare. When later
      rejection occurs, it is at a median of 10 weeks after a transplant. Two of the 3
      early rejections were antibody mediated. Later rejections were associated with
      subtherapeutic immunosuppression and donors after cardiac death. Biopsies need
      not be performed during the early postoperative period when anti-thymocyte
      globulin is used with tacrolimus, mycophenolate mofetil, and steroids.

PMID- 22631059
TI  - Detection of antibodies against major histocompatibility complex class I-related
      chain A in long-term renal graft recipients.
AB  - OBJECTIVES: To determine the prevalence, allele specificity, and intensity of
      anti-MICA antibodies in long-term renal graft recipients and to investigate their
      association with impaired renal function. MATERIALS AND METHODS: Sixty-eight long
      term (> 10 y) renal graft recipients were divided into 2 groups: (1) patients
      with impaired renal function (serum creatinine >= 2 mg/dL, n=6); (2) patients
      with normal renal function (serum creatinine < 176.8 MUmol/L, n=62). Anti-MICA
      antibodies were tested using Luminex single antigen beads assays and the
      frequency, specificity, and intensity of these antibodies were compared between 2
      patient groups. RESULTS: MICA antibodies were detected in 33% of impaired renal
      function patients and 15% of normal renal function patients (P > .05). Anti
      MICA*027 antibodies were found in 11.76% of patients, whereas antibody to
      MICA*012 was found in 2.94% of patients. Interestingly, among all antibody
      specificities, MICA*001,*004, *007, *009, *012, and *018 were found more
      frequently in impaired renal function patients than in normal renal function
      patients. The peak mean fluorescence intensity levels of MICA antibodies in
      impaired renal function patients were significantly higher than those in normal
      renal function patients (P < .05). CONCLUSIONS: Our data suggest that increased
      prevalence and intensity of anti-MICA antibodies are associated with impaired
      renal graft function in long-term renal graft recipients and some MICA antibodies
      might be more important than others in mediating graft rejection.

PMID- 22631060
TI  - Neurologic complications of renal transplant.
AB  - OBJECTIVES: Neurologic problems have a major effect on the survival and quality
      of life in renal transplant recipients. This study sought to review the incidence
      and character of neurologic complications after renal transplant. MATERIALS AND
      METHODS: Medical records of 319 renal transplant recipients admitted to the
      Transplant Outpatient Clinic were reviewed retrospectively for neurologic
      complications. RESULTS: Of the 319 transplant recipient patients reviewed, 124
      patients (39%) were women and 193 patients (61%) were men. The mean patient age
      was 41 +/- 11 years, and the transplanted kidney was received from deceased
      donors in 161 patients (51%) and living donors in 158 patients (49%). There were
      50 patients (16%) who had neurologic complications, most commonly herpes zoster
      infection associated with immunosuppressive medication. Only 1 patient, who had
      glioblastoma multiforme, died. Treatment included corticosteroids in 296 patients
      (93%) and calcineurin inhibitors (including tacrolimus) in 111 patients (35%).
      CONCLUSIONS: Neurologic complications are common after renal transplant. Most
      complications are associated with immunosuppressive medications.

PMID- 22631061
TI  - Partial portal arterialization for hepatic arterial thrombosis after living-donor
      liver transplant.
AB  - OBJECTIVES: The most serious, life-threatening complication after living-donor
      liver transplant is a hepatic arterial thrombosis. Although possible therapies
      for acute hepatic arterial thrombosis include revascularization to salvage the
      graft, or retransplant, these may be difficult to perform owing to technical
      aspects and donor shortages. Previously, we reported the usefulness of partial
      portal arterialization in such cases. MATERIALS AND METHODS: Four cases of
      partial portal arterialization for hepatic arterial occlusion after living-donor
      liver transplant were reviewed. The surgical procedure of partial portal
      arterializations involves making an arteriovenous shunt via a side-to-side
      anastomosis, using mesenteric vessels approximately 2 mm in diameter. RESULTS:
      After partial portal arterialization, hepatic arterial flow was not detected, but
      graft injury owing to hypoxia gradually improved in all cases. In 1 case,
      occlusion of the arteriovenous shunt itself and the collateral artery to the
      graft were identified by angiography 45 days after partial portal
      arterialization. In another case, massive ascites, pleural effusion, and variceal
      changes of the mesenteric veins owing to portal hypertension were identified, and
      surgical closure of the shunt was performed 152 days after partial portal
      arterialization. In the other 2 cases, there were no definite problems related to
      partial portal arterialization, but the patients died owing to other
      complications. CONCLUSIONS: When hepatic arterial thrombosis occurs after living
      donor liver transplant, revascularization should be performed first. However,
      this sometimes may be difficult, as when the arterial dissection reaches into the
      graft. Partial portal arterialization is an easy and effective surgical
      procedure. Therefore, partial portal arterialization appears to be a useful
      option to gain time until collateral arterial vessels develop or retransplant,
      even if revascularization cannot be performed.

PMID- 22631062
TI  - Serum insulinlike growth factor-1 and its binding protein-3 levels in children
      with cirrhosis waiting for a liver transplant.
AB  - OBJECTIVES: Investigate the prognostic value of serum insulinlike growth factor-1
      (IGF-1) and its binding protein 3 (IGFBP-3) in pediatric patients with liver
      cirrhosis, and investigate the correlation between these parameters and other
      available prognostic factors including Child-Pugh scoring, Pediatric End-Stage
      Liver Disease, and Mayo End-Stage Liver Disease scoring. MATERIALS AND METHODS:
      This prospective, case-controlled study was done at the Nemazee hospital for 12
      months from August 2009 to August 2010. It included 45 pediatric patients (< 18
      years) diagnosed with liver cirrhosis and 38 healthy age and sex-matched
      controls. The extent and severity of the liver disease was evaluated by the Child
      Pugh classification and Pediatric End-Stage Liver Disease/Mayo End-Stage Liver
      Disease scores. Serum levels of IGF-1 and IGFBP-3 were determined and were
      compared to controls and their correlation with Child-Pugh and Pediatric End
      Stage Liver Disease/Mayo End-Stage Liver Disease scores were investigated.
      RESULTS: The most-common cause of liver cirrhosis was biliary atresia being found
      in 11 patients (24.4%) followed by tyrosinemia in 8 (17.8%). IGF-1 serum levels
      were significantly lower in cirrhotic patients compared with controls (3.85 +/-
      3.69 nmol/L vs 41.79 +/- 16.03 nmol/L; P < .001). Serum levels of IGFBP-3 also
      were significantly lower in patients with liver cirrhosis compared with healthy
      controls (46.66 +/- 30.57 nmol/L vs 205.63 +/- 25.52 nmol/L; P < .001). Serum
      levels of IGF-1 were significantly lower in patients with stage B (P = .047) and
      C (P = .036) of Child-Pugh classification compared with stage A. Serum levels of
      IGF-1 (r ~ 0.227; P = .034) and IGFBP-3 (r ~ 0.389; P = .008) were negatively
      correlated with Pediatric End-stage Liver Disease / Mayo End-stage Liver Disease
      scores. CONCLUSIONS: The serum levels of IGF-1 and IGFBP-3 are decreased in
      children with liver cirrhosis. The stage of liver dysfunction is correlated to
      serum levels of IGF-1 and IGFBP-3 in children. Thus, these 2 factors can be used
      for assessing the prognosis and outcome in those children with liver cirrhosis.

PMID- 22631063
TI  - Twenty-four hour steroid avoidance immunosuppressive regimen in liver transplant
      recipients.
AB  - OBJECTIVES: To investigate the efficacy and safety of an immunosuppressive
      regimen of steroid avoidance in combination with induction therapy and tacrolimus
      in liver transplant recipients. MATERIALS AND METHODS: Eighty-two adult liver
      transplant recipients were randomized into 2 groups: standard protocol group
      (n=41) in which steroids were withdrawn 3 months after the operation, and a 24
      hour steroid avoidance group (n=41) in which steroids were eliminated within 24
      hours. The incidence of acute rejections, infections (bacterial, fungal, and
      cytomegalovirus), and metabolic complications were analyzed between the groups.
      RESULTS: The incidence of early posttransplant diabetes mellitus and the average
      dosage of insulin consumption among diabetic recipients were significantly higher
      in recipients in the standard protocol group than in the 24-hour avoidance group
      (P < .05). In addition, the incidence of hypertension and infection during the
      follow-up were also higher in patients of the standard protocol group (P < .05).
      The incidence of hypertension in the early posttransplant period, hyperlipemia,
      and acute rejection during the follow-up were comparable between the groups (P >
      .05). CONCLUSIONS: Twenty-four hour steroid avoidance combined with induction
      therapy and tacrolimus maintenance is a safe and efficient immunosuppression
      strategy that can significantly reduce posttransplant infections and other
      complications owing to long-term use of steroids, without increasing the risk of
      acute rejection.

PMID- 22631064
TI  - Autotransplanting of bone marrow-derived mononuclear cells for complete cases of
      canine paraplegia and loss of pain perception, secondary to intervertebral disc
      herniation.
AB  - OBJECTIVES: Severe intervertebral disc herniation causes complete paraplegia and
      loss of pain sensation in canines. The prognosis is poor, even when decompression
      surgery is performed immediately after onset. Studies suggest that bone marrow
      derived mononuclear cells will regenerate the injured spinal cord and restore
      neurologic function. This study was conducted to assess the clinical efficacy of
      bone marrow-derived mononuclear cell autotransplanting in severe cases of canine
      intervertebral disc herniation. MATERIALS AND METHODS: Eighty-two dogs (miniature
      dachshunds) with severe thoracolumbar intervertebral disc herniation were used.
      All had intervertebral disc herniation accompanied by paraplegia and loss of pain
      perception. In 36 dogs, bone marrow-derived mononuclear cells were
      autotransplanted to the lesioned spinal cord immediately after decompression
      surgery. Bone marrow was collected from the proximal humerus and subjected to
      density gradient centrifugation to isolate the bone marrow-derived mononuclear
      cells. The remaining 46 dogs (receiving surgical treatment only) were assigned as
      controls. Therapeutic efficacy was compared based on the rate of ambulatory
      recovery. RESULTS: Ambulatory recovery was observed in 88.9% and 56.5% of animals
      in the bone marrow-derived mononuclear cells and control groups, and a
      significant difference was found. No complications were found in bone marrow
      derived mononuclear cells group. CONCLUSIONS: Bone marrow-derived mononuclear
      cell transplanting revealed a significant increase in the recovery rate and, as
      has been reported in rats and humans, bone marrow-derived mononuclear cell
      autotransplanting shows efficacy in canines as well.

PMID- 22631065
TI  - Everolimus in different combinations as maintenance immunosuppressive therapy in
      heart transplant recipients.
AB  - OBJECTIVES: We examined the experiences of heart transplant recipients receiving
      everolimus as maintenance therapy in different combinations over a long time.
      MATERIALS AND METHODS: Between 2004 and 2009, forty patients (29 men, 11 women;
      mean age, 51.6 y) were switched from a routine immunosuppressive regimen to
      everolimus. Indications were other (2), renal insufficiency (17), cardiac
      allograft vasculopathy (14), and ongoing cellular rejection (7). Combinations
      were either along with cyclosporine (24), mycophenolate mofetil (14), or others
      (2). Indications for the introduction of everolimus including safety, efficacy,
      different combinations of everolimus, biopsy-proven acute rejections, renal
      function, and infections were evaluated retrospectively. RESULTS: Five patients
      died, 4 of them were still on everolimus at the time of death; they died from
      intracerebral hemorrhage (1), embolism (1), cardiac arrest (2), and unknown (1).
      Everolimus was discontinued in 6 patients owing to severe adverse effects: Edema
      (2), gastrointestinal adverse effects (3), and dermal adverse effects (1). Mean
      everolimus trough levels were 5.8 MUmol/L at 6 months and 4.9 at 60 months. Mean
      cyclosporine levels were 67.62 MUmol/L at 6 months and 47.3 MUmol/L at 60 months.
      Mean serum creatinine levels were stable (147.9 MUmol/L after 60 months). Four
      life-threatening infections (all pneumonia) occurred but resulted in complete
      recovery. CONCLUSIONS: Everolimus is safe with different immunosuppressive
      combinations after receiving a heart transplant.

PMID- 22631066
TI  - Comparison of serum and bronchoalveolar lavage galactomannan in diagnosing
      invasive aspergillosis in solid-organ transplant recipients.
AB  - OBJECTIVES: This study sought to compare the sensitivities of serum galactomannan
      and bronchoalveolar lavage galactomannan in diagnosing invasive aspergillosis in
      solid-organ transplant recipients (lung and heart). MATERIALS AND METHODS: This
      study took place in the lung transplant center of the National Research Institute
      for Tuberculosis and Lung Disease. All patients with clinical and radiologic
      manifestations suggestive of pulmonary infection were included. Serum and
      bronchoalveolar lavage galactomannan were measured. RESULTS: Seventeen patients
      were included (lung, 15; heart, 1; heart-lung, 1). Probable or definite invasive
      aspergillosis was diagnosed in 9 patients. With a cutoff >= 0.5, serum
      galactomannan sensitivity and specificity for diagnosing invasive aspergillosis
      were 77.18% and 100%. Negative predictive value and positive predictive value
      were 80% and 100%. The sensitivity and specificity of bronchoalveolar lavage
      galactomannan for diagnosing invasive aspergillosis with cutoff of >= 0.5 was
      100%. CONCLUSIONS: Regarding the high levels of mortality and problems in
      diagnosing this disease, using bronchoalveolar lavage galactomannan could be a
      suitable option.

PMID- 22631067
TI  - Prevention and management of graft thrombosis in pancreatic transplant.
AB  - Pancreatic transplant effectively cures type 1 diabetes mellitus and maintains
      consistent long-term euglycemia. However, technical failure, and in particular
      graft thrombosis, accounts for the vast majority of transplants lost in the early
      postoperative period. The pancreas' inherently low microvascular flow state makes
      it vulnerable to vascular complications, as does the hypercoagulable blood of
      diabetic patients. Ultimately, the phenomenon is most definitely multifactorial.
      Prevention, as opposed to treatment, is key and should focus on reducing these
      multiple risk factors. This will involve tactical donor selection, optimal
      surgical technique and some form of anticoagulation. Close monitoring and early
      intervention will be crucial when treating thrombosis once preventative methods
      have failed. This may be achieved by further anticoagulation, graft salvage, or
      pancreatectomy with retransplant. This article will explore the multiple factors
      contributing to graft thrombus formation and the ways in which they may be
      addressed to firstly prevent, or more likely, reduce thrombosis. Secondly, we
      will consider the management strategies which can be implemented once thrombosis
      has occurred.

PMID- 22631068
TI  - Successful transplant of a kidney with fibromuscular dysplasia having higher
      glomerular filtration rate than the contralateral kidney.
AB  - Fibromuscular dysplasia is the second-most commonly encountered anatomic
      abnormality in potential renal donors. Normotensive patients with medial
      fibroplasia and low-grade lesions have been used as renal donors. However, no
      studies have reported the optimal choice of a kidney for donation where the
      kidney with fibromuscular dysplasia had a larger volume and a higher glomerular
      filtration rate than the unaffected side. Herein, we report a case of renal
      transplant using a kidney with fibromuscular dysplasia that had higher glomerular
      filtration rate than the normal side. After transplant, hypertension and abnormal
      serum creatinine did not occur in either the donor or the recipient during 12
      months' follow-up.

PMID- 22631069
TI  - Renal artery aneurysm in robotic donor nephrectomy: a case report.
AB  - OBJECTIVES: With the current disparity between donor organ availability and
      recipient need, creative techniques help optimize the use of available organs. We
      present a case of a woman, who was worked-up as a kidney donor, who was
      incidentally found to have a saccular aneurysm on her renal artery. The patient
      was asymptomatic, normotensive, and had normal renal function. MATERIALS AND
      METHODS: We performed a laparoscopic robotic donor nephrectomy, repaired the
      aneurysm on the back table, and transplanted the organ into the recipient.
      RESULTS: The donor underwent a successful robotic nephrectomy, successfully
      eradicating any risk of aneurysmal complications; the recipient received an
      anatomically normal organ with excellent function. CONCLUSIONS: An altruistic act
      by the donor identified a potentially fatal lesion, which was not only remedied,
      but the intended donation proceeded when a creative approach was used.

PMID- 22631070
TI  - Everolimus-induced lymphedema in a renal transplant recipient: a case report.
AB  - The mammalian target of rapamycin inhibitors is commonly preferred for solid
      organs for transplantation. Although these drugs have various adverse effects,
      sirolimus-related lymphedema has been rarely reported. We report a case of
      lymphedema related to everolimus after a kidney transplant. A 60-year-old woman
      successfully received a deceased-donor kidney. Everolimus was added to the
      treatment in postoperative month 3 owing to other immunosuppressive drugs'
      adverse effects. Edema occurred first on her feet in the first year after the
      transplant. During 3 months' follow-up, with no immunosuppressive adjustment, the
      edema progressed. Diagnosis of lymphedema was established. Several weeks after
      discontinuing everolimus, the patient's lymphedema began to resolve itself and
      completely disappeared in 3 months. The mammalian target of rapamycin inhibitors
      rarely causes lymphedema by inhibiting different subtypes of vascular endothelial
      growth factors, which results in impaired lymphangiogenesis. While there are few
      reports about sirolimus-related lymphedema, this case represents the first
      everolimus-related case of lymphedema. Further studies are warranted to explain
      the underlying mechanisms.

PMID- 22631071
TI  - Kidney transplant after preexisting posterior reversible encephalopathy syndrome
      induced by Goodpasture's syndrome.
AB  - Posterior reversible encephalopathy syndrome is characterized by varying
      neurologic symptoms associated with brain vasogenic edema. Posterior reversible
      encephalopathy syndrome can be associated with severe hypertension (eg, in
      eclampsia or HELLP syndrome), but it also has been observed without hypertension
      and in several clinical conditions including infections and autoimmune disorders.
      The literature offers several reports of posterior reversible encephalopathy
      syndrome detected or induced after bone-marrow and solid-organ transplant, or
      induction by immunosuppression. We describe what is, to the best of our
      knowledge, the first case of man who successfully underwent a kidney transplant
      with preexisting posterior reversible encephalopathy syndrome induced by
      Goodpasture's syndrome.

PMID- 22631072
TI  - Three aspects are critical for carrying out intraportal islet transplants
      successfully in a diabetes mouse model.

PMID- 22631073
TI  - Dosing and effectiveness of recombinant activated factor VII (rFVIIA) in
      congenital haemophilia with inhibitors by bleed type and location: the experience
      of the Haemophilia and Thrombosis Research Society (HTRS) Registry (2004-2008).
AB  - Control of bleeding in patients with congenital haemophilia with inhibitors
      requires use of bypassing agents such as recombinant activated factor VII
      (rFVIIa). Due to the difficulties in performing prospective clinical trials in
      this small subgroup of patients with haemophilia and the need for postmarketing
      surveillance, a large-scale database was developed by the Hemophilia and
      Thrombosis Research Society. This report comprises an analysis of the database
      with respect to assessing dosing and efficacy of rFVIIa by bleed type and
      location. Between January 2004 and November 2008, data from 129 inhibitor
      patients with 2041 rFVIIa-treated bleeds were analysed. The bleeds were primarily
      spontaneous (58%) and traumatic (30%). The most common locations were joints
      (57%), muscle (20%), mucosal (7%) and subcutaneous (6%). Median total rFVIIa
      doses per bleeding episode for spontaneous and traumatic bleeds were 540 mcg kg(
      1) (4 injections/2 days) and 300 mcg kg(-1) (2.5 injections/1 day) respectively.
      Median total rFVIIa dose (mean dose, number of injections) was 480 mcg kg(-1)
      (110 mcg kg(-1) , 3) for joint; 557 mcg kg(-1) (120 mcg kg(-1) , 4) for muscle;
      360 mcg kg(-1) (120 mcg kg(-1) , 3) for mucosal and 402 mcg kg(-1) (117 mcg kg(
      1) , 3) for subcutaneous. Overall efficacy ranged from 89% to 93%; bleeding
      stopped in 89% of spontaneous and 93% of traumatic bleeds, 90% of joint bleeds,
      and 89% of muscle, mucosal,and subcutaneous bleeds. Although spontaneous bleeds
      require slightly higher doses than traumatic bleeds, most bleeds were treated
      with a median of 3-4 injections (110-130 mcg kg(-1) ). Effectiveness of rFVIIa
      was consistently high across bleeding types and locations.

PMID- 22631074
TI  - Determination of primary sequence specificity of Arabidopsis MAPKs MPK3 and MPK6
      leads to identification of new substrates.
AB  - MAPKs (mitogen-activated protein kinases) are signalling components highly
      conserved among eukaryotes. Their diverse biological functions include cellular
      differentiation and responses to different extracellular stress stimuli. Although
      some substrates of MAPKs have been identified in plants, no information is
      available about whether amino acids in the primary sequence other than proline
      directed phosphorylation (pS-P) contribute to kinase specificity towards
      substrates. In the present study, we used a random positional peptide library to
      search for consensus phosphorylation sequences for Arabidopsis MAPKs MPK3 and
      MPK6. These experiments indicated a preference towards the sequence L/P-P/X-S-P
      R/K for both kinases. After bioinformatic processing, a number of novel candidate
      MAPK substrates were predicted and subsequently confirmed by in vitro kinase
      assays using bacterially expressed native Arabidopsis proteins as substrates.
      MPK3 and MPK6 phosphorylated all proteins tested more efficiently than did
      another MAPK, MPK4. These results indicate that the amino acid residues in the
      primary sequence surrounding the phosphorylation site of Arabidopsis MAPK
      substrates can contribute to MAPK specificity. Further characterization of one of
      these new substrates confirmed that At1g80180.1 was phosphorylated in planta in a
      MAPK-dependent manner. Phenotypic analyses of Arabidopsis expressing
      phosphorylation site mutant forms of At1g80180.1 showed clustered stomata and
      higher stomatal index in cotyledons expressing the phosphomimetic form of
      At1g80180.1, providing a link between this new MAPK substrate and the defined
      role for MPK3 and MPK6 in stomatal patterning.

PMID- 22631075
TI  - Expression of nucleophosmin/NPM1 correlates with migration and invasiveness of
      colon cancer cells.
AB  - BACKGROUND: We aimed to examine the expression level of Nucleophosmin (NPM1)
      protein in colon cancer tissues and to investigate the potential role of NPM1 in
      the regulation of cell migration and invasiveness. METHODS: Immunohistochemical
      assay was performed to examine the expression pattern of NPM1 in 31 groups of
      colonic carcinoma samples, including colon tumors, adjacent normal tissues, and
      matched metastatic lymph nodes from the same patients. Small interfering RNA
      technique and exogenous expression of wild type NPM1 methods were used to further
      verify the function of NPM1. RESULTS: High-expression of NPM1 correlates with
      lymph node metastasis (P = 0.0003) and poor survival rate of human colon cancer
      patients (P = 0.017). SiRNA-mediated reduction of NPM1 was also shown to inhibit
      the migration and invasiveness of metastatic colon cancer HCT116 cell line. In
      addition, the exogenous expression of NPM1 in HT29 cells, a NPM1 low expression
      and low invasive colon cancer cell line, enhanced cell migration and invasiveness
      along with increased cell proliferation. CONCLUSIONS: The current study uncovered
      the critical role of NPM1 in the regulation of colon cancer cells migration and
      invasion, and NPM1 may serve as a potential marker for the prognosis of colon
      cancer patients.

PMID- 22631076
TI  - On mentoring.

PMID- 22631077
TI  - Follow-up of a modified Fontan randomized trial for intraatrial reentrant
      tachycardia prophylaxis.
AB  - OBJECTIVE:   Atrial arrhythmias represent significant morbidity and risk for
      mortality in Fontan patients. In a randomized trial involving patients undergoing
      a lateral tunnel Fontan between 1999 and 2001, Collins et al. investigated the
      safety and efficacy of a surgical atrial incision aimed at decreasing the
      incidence of intraatrial reentrant tachycardia (IART). The purpose of this study
      was to report the late follow-up of the aforementioned trial. DESIGN:   All
      surviving patients previously enrolled in the randomized trial were eligible for
      this follow-up study. Patients' legal guardians were contacted for informed
      consent and data were obtained form a retrospective chart review. RESULTS:   Of
      the 39 eligible patients, 29 were recruited: 15 in the intervention and 14 in the
      control groups. The median follow was 9.0 (1.2) years for the intervention group
      and 9.3 (1.1) years for the control group (P= .86). At most recent follow-up,
      there was no statistically significant difference in the demographic,
      echocardiographic, and electrophysiological data between the two groups. There
      was no late incidence of the primary outcome, IART. There were nine cases of late
      onset sinus node dysfunction (SND): 5/15 in the intervention and 4/14 in the
      control groups (P= .99). There was only one late pacemaker implantation for early
      post-op SND. CONCLUSION:   At late follow-up 9 years post-Fontan, IART had not
      occurred in either group. There was no evidence of late-onset complications
      related to the interventional atrial incision. Further follow-up is warranted for
      this cohort.

PMID- 22631079
TI  - Structure, Motion, Interaction and Expression of Biological Macromolecules.

PMID- 22631210
TI  - Investigation of adsorption behavior of mercury on Au(111) from first principles.
AB  - The structural and electronic properties of Hg, SO(2), HgS, and HgO adsorption on
      Au(111) surfaces have been determined using density functional theory with the
      generalized gradient approximation. The adsorption strength of Hg on Au(111)
      increases by a factor of 1.3 (from -9.7 to -12.6 kcal/mol) when the number of
      surface vacancies increases from 0 to 3; however, the adsorption energy decreases
      with more than three vacancies. In the case of SO(2) adsorption on Au(111), the
      Au surface atoms are better able to stabilize the SO(2) molecule when they are
      highly undercoordinated. The SO(2) adsorption stability is enhanced from -0.8 to 
      9.3 kcal/mol by increasing the number of vacancies from 0 to 14, with the lowest
      adsorption energy of -10.2 kcal/mol at 8 Au vacancies. Atomic sulfur and oxygen
      precovered-Au(111) surfaces lower the Hg stability when Hg adsorbs on the top of
      S and O atoms. However, a cooperative effect between adjacent Hg atoms is
      observed as the number of S and Hg atoms increases on the perfect Au(111)
      surface, resulting in an increase in the magnitude of Hg adsorption. Details of
      the electronic structure properties of the Hg-Au systems are also discussed.

PMID- 22631211
TI  - Synchrotron photoionization measurements of OH-initiated cyclohexene oxidation:
      ring-preserving products in OH + cyclohexene and hydroxycyclohexyl + O2
      reactions.
AB  - Earlier synchrotron photoionization mass spectrometry experiments suggested a
      prominent ring-opening channel in the OH-initiated oxidation of cyclohexene,
      based on comparison of product photoionization spectra with calculated spectra of
      possible isomers. The present work re-examines the OH + cyclohexene reaction,
      measuring the isomeric products of OH-initiated oxidation of partially and fully
      deuterated cyclohexene. In particular, the directly measured photoionization
      spectrum of 2-cyclohexen-1-ol differs substantially from the previously
      calculated Franck-Condon envelope, and the product spectrum can be fit with no
      contribution from ring-opening. Measurements of H(2)O(2) photolysis in the
      presence of C(6)D(10) establish that the addition-elimination product
      incorporates the hydrogen atom from the hydroxyl radical reactant and loses a
      hydrogen (a D atom in this case) from the ring. Investigation of OH + cyclohexene
      4,4,5,5-d(4) confirms this result and allows mass discrimination of different
      abstraction pathways. Products of 2-hydroxycyclohexyl-d(10) reaction with O(2)
      are observed upon adding a large excess of O(2) to the OH + C(6)D(10) system.

PMID- 22631212
TI  - Musings about regulation by T-suppressors: a response to the commentary by
      Kristofor Ellestad on 'Meanderings into the regulation of effector class by the
      immune system: derivation of the trauma model'.
AB  - Any discussion of the regulation of effector class must include feedback control
      on the magnitude of the response. The induced effector activities are
      biodestructive and ridding. They are, in and of themselves, unspecific with
      respect to self and nonself. Consequently all responses include some level of
      innocent bystander pathology. The regulation of magnitude is essential to keeping
      this level of pathology at an evolutionarily acceptable level. This is my
      postulated role of suppressor T-cells, more popularly referred to as Treg. In
      order to perform this function they must be somatically selected to be anti
      nonself like all other T/B-cells. If correct, any role that they might play in
      determining normal tolerance is excluded. As the commentary of Ellestad
      illustrates, their function to regulate autoimmunity is the consensus view today
      and, therefore, this competing concept and my analysis of suggested papers should
      invite a wide ranging debate.

PMID- 22631213
TI  - Could microRNAs be biomarkers for neural tube defects?

PMID- 22631214
TI  - Urolithins are the main urinary microbial-derived phenolic metabolites
      discriminating a moderate consumption of nuts in free-living subjects with
      diagnosed metabolic syndrome.
AB  - Walnuts ( Juglans regia  L.), hazelnuts ( Corylus avellana  L.), and almonds (
      Prunus dulcis  Mill.) are rich sources of ellagitannins and proanthocyanidins.
      Gut microbiota plays a crucial role in modulating the bioavailability of these
      high molecular weight polyphenols. However, to date there are no studies
      evaluating the capacity to produce nut phenolic metabolites in subjects with
      metabolic syndrome (MetS), a pathology associated with an altered gut bacterial
      diversity. This study applied a LC-MS targeted approach to analyze the urinary
      excretion of nut phenolic metabolites in MetS subjects following 12 weeks of nut
      consumption, compared to sex- and age-matched individuals given a nut-free
      control diet. Metabolites were targeted in both hydrolyzed and nonhydrolyzed
      urine by LC-PDA-QqQ-MS/MS analysis, and identification of metabolites lacking
      available standards was confirmed by LC-ESI-ITD-FT-MS. Ellagitannin-derived
      urolithins A and B significantly increased after the nut-enriched-diet,
      urolithins C and D were also detected, and a complex combination of urolithin
      conjugated forms was observed in nonhydrolyzed urine, confirming an extensive
      phase II metabolism after absorption. In contrast, no significant increases in
      proanthocyanidin microbial metabolites were observed in urine following nut
      consumption. Because the intestinal microbiota of the subjects in this study
      could catabolize ellagitannins into a wide range of urolithins, further research
      is strongly warranted on the in vivo potential of these microbial metabolites in
      reducing cardiometabolic risk.

PMID- 22631215
TI  - Heparin-induced thrombocytopenia in a hemodialysis patient treated with
      fondaparinux: nephrologists between two fires.
AB  - Heparin-induced thrombocytopenia (HIT) is caused by heparin exposure and presents
      with reduced platelet count. Patients undergoing hemodialysis (HD) treatment have
      increased risk of developing HIT due to prolonged exposure to unfractionated
      heparin or low-molecular weight heparin. We report a 79-year-old male patient
      with end-stage renal disease who developed type-II HIT during maintenance HD.
      Platelet count of the patient decreased gradually and antiplatelet factor IV
      antibody was found to be positive. The patient was treated with fondaparinux and
      continued heparin-free HD. Unfortunately, despite favorable initial response
      without any thrombotic episodes, the patient died due to severe sepsis
      complicated by gastrointestinal hemorrhage.

PMID- 22631216
TI  - The genetics of environmental variation of dry matter grain yield in maize.
AB  - Dry matter grain yield per plot from three genetically homogeneous single-cross
      maize hybrids were analysed to investigate whether environmental variance depends
      on genotype. Three genotypes were tested at 20 locations in 3 years. The data
      were analysed using a non-parametric approach and fully parametric Bayesian
      models. Both analyses reveal effects of genotype on environmental variation. The
      Bayesian analyses indicate that genotype by location-year interactions are the
      most important effects acting at the level of the mean. The best-fitting Bayesian
      model is one postulating genotype by location-year interactions acting on the
      mean and main effects of genotype and of location-year on the variance. Despite
      the detection of genotypic effects acting on the variance, location-year effects
      constitute the biggest relative source of variance heterogeneity.

PMID- 22631217
TI  - Ammonium transporters achieve charge transfer by fragmenting their substrate.
AB  - Proteins of the Amt/MEP family facilitate ammonium transport across the membranes
      of plants, fungi, and bacteria and are essential for growth in nitrogen-poor
      environments. Some are known to facilitate the diffusion of the neutral NH(3),
      while others, notably in plants, transport the positively charged NH(4)(+). On
      the basis of the structural data for AmtB from Escherichia coli , we illustrate
      the mechanism by which proteins from the Amt family can sustain electrogenic
      transport. Free energy calculations show that NH(4)(+) is stable in the AmtB
      pore, reaching a binding site from which it can spontaneously transfer a proton
      to a pore-lining histidine residue (His168). The substrate diffuses down the pore
      in the form of NH(3), while the excess proton is cotransported through a highly
      conserved hydrogen-bonded His168-His318 pair. This constitutes a novel permeation
      mechanism that confers to the histidine dyad an essential mechanistic role that
      was so far unknown.

PMID- 22631218
TI  - Barriers to implementation of stroke rehabilitation evidence: findings from a
      multi-site pilot project.
AB  - PURPOSE: To describe the barriers to implementation of evidence-based
      recommendations (EBRs) for stroke rehabilitation experienced by nurses,
      occupational therapists, physical therapists, physicians and hospital managers.
      METHODS: The Stroke Canada Optimization of Rehabilitation by Evidence project
      developed EBRs for arm and leg rehabilitation after stroke. Five Canadian stroke
      inpatient rehabilitation centers participated in a pilot implementation study. At
      each site, a clinician was identified as the "local facilitator" to promote the 6
      month implementation. A research coordinator observed the process. Focus groups
      done at completion were analyzed thematically for barriers by two raters.
      RESULTS: A total of 79 rehabilitation professionals (23 occupational therapists,
      17 physical therapists, 23 nurses and 16 directors/managers) participated in 21
      focus groups of three to six participants each. The most commonly noted barrier
      to implementation was lack of time followed by staffing issues,
      training/education, therapy selection and prioritization, equipment availability
      and team functioning/communication. There was variation in perceptions of
      barriers across stakeholders. Nurses noted more training and staffing issues and
      managers perceived fewer barriers than frontline clinicians. CONCLUSIONS:
      Rehabilitation guideline developers should prioritize evidence for implementation
      and employ user-friendly language. Guideline implementation strategies must be
      extremely time efficient. Organizational approaches may be required to overcome
      the barriers. [Box: see text].

PMID- 22631219
TI  - Compulsory and voluntary admission in psychiatric hospitals in northern Norway
      2009-2010. A national registry-based analysis.
AB  - BACKGROUND: During the last decade, Norwegian healthcare authorities have been
      concerned about the frequent use of coercive measures in psychiatric care. On
      this background, we aimed to explore the voluntary and compulsory admissions in
      psychiatric hospitals in northern Norway, the University Hospital of North Norway
      in Tromso (UNN-T) and the Nordland Hospital in Bodo (NH-B). METHODS: All
      voluntary and compulsory admissions (2009-2010) among patients aged >=18 years
      registered by the Norwegian Patient Registry (NPR) were analyzed retrospectively.
      Compulsory admission was registered according to the general practitioner's
      (GP's) decision and the patients were hospitalized in Bodo or Tromso. A total of
      12,237 admissions and 242,148 days in hospital were identified. The female/male
      ratio of admission and stay was 1.17 and 1.15, respectively. RESULTS: The
      admission rate (northern Norway =1.0) varied significantly from south to north
      (0.60-1.52). Whereas patients living close to the hospitals had the same
      admission rate as others, the mean hospital stay was significantly longer (ratio
      =1.32). Furthermore, the UNN-T had a higher re-admission rate (2% vs. 5%).
      Municipalities with District Psychiatric Centers (DPC) did not differ from
      others. A significant difference in the use of coercive measures was revealed
      between hospitals. Forced medication was the most frequent measure employed.
      CONCLUSIONS: The study documented a south-north gradient in admission rate and
      indicated differences in the use of coercion. Variation may partly be due to
      different reporting procedures. This finding and why patients living in the
      neighborhood of hospitals stay longer should be explored in future studies.

PMID- 22631220
TI  - Development of a dense SNP-based linkage map of an apple rootstock progeny using
      the Malus Infinium whole genome genotyping array.
AB  - BACKGROUND: A whole-genome genotyping array has previously been developed for
      Malus using SNP data from 28 Malus genotypes. This array offers the prospect of
      high throughput genotyping and linkage map development for any given Malus
      progeny. To test the applicability of the array for mapping in diverse Malus
      genotypes, we applied the array to the construction of a SNP-based linkage map of
      an apple rootstock progeny. RESULTS: Of the 7,867 Malus SNP markers on the array,
      1,823 (23.2%) were heterozygous in one of the two parents of the progeny, 1,007
      (12.8%) were heterozygous in both parental genotypes, whilst just 2.8% of the 921
      Pyrus SNPs were heterozygous. A linkage map spanning 1,282.2 cM was produced
      comprising 2,272 SNP markers, 306 SSR markers and the S-locus. The length of the
      M432 linkage map was increased by 52.7 cM with the addition of the SNP markers,
      whilst marker density increased from 3.8 cM/marker to 0.5 cM/marker. Just three
      regions in excess of 10 cM remain where no markers were mapped. We compared the
      positions of the mapped SNP markers on the M432 map with their predicted
      positions on the 'Golden Delicious' genome sequence. A total of 311 markers
      (13.7% of all mapped markers) mapped to positions that conflicted with their
      predicted positions on the 'Golden Delicious' pseudo-chromosomes, indicating the
      presence of paralogous genomic regions or mis-assignments of genome sequence
      contigs during the assembly and anchoring of the genome sequence. CONCLUSIONS: We
      incorporated data for the 2,272 SNP markers onto the map of the M432 progeny and
      have presented the most complete and saturated map of the full 17 linkage groups
      of M. pumila to date. The data were generated rapidly in a high-throughput semi
      automated pipeline, permitting significant savings in time and cost over linkage
      map construction using microsatellites. The application of the array will permit
      linkage maps to be developed for QTL analyses in a cost-effective manner, and the
      identification of SNPs that have been assigned erroneous positions on the 'Golden
      Delicious' reference sequence will assist in the continued improvement of the
      genome sequence assembly for that variety.

PMID- 22631221
TI  - Medial transconjunctival intrinsic optic nerve biopsy: surgical technique and
      indications.
AB  - AIM: To describe a method of intrinsic optic nerve biopsy and its indications.
      METHODS: Retrospective case series. RESULTS: We report four cases that required
      intrinsic optic nerve biopsy for progressive optic neuropathy with uncertain
      diagnosis after negative systemic investigations. In all cases, a medial
      transconjunctival approach was used. There were no complications noted with this
      technique in the series, specifically there was no reported deterioration in
      vision. One case of neurosarcoidosis was confirmed. In the other three cases, the
      pathology results were non-diagnostic but ruled out serious causes such as
      central nervous system leukaemia relapse. CONCLUSION: Medial transconjunctival
      intrinsic optic nerve biopsy is a minimally invasive and safe technique. The
      technique is suitable for sampling pathology in the distal portion of the optic
      nerve. Optic nerve biopsy is indicated when there is significant loss of vision
      from an isolated optic nerve disease and all systemic investigations have failed
      to identify the cause, or where the clinical course of a presumed diagnosis is
      atypical.

PMID- 22631222
TI  - Autonomous motion of metallic microrods propelled by ultrasound.
AB  - Autonomously moving micro-objects, or micromotors, have attracted the attention
      of the scientific community over the past decade, but the incompatibility of
      phoretic motors with solutions of high ionic strength and the use of toxic fuels
      have limited their applications in biologically relevant media. In this letter we
      demonstrate that ultrasonic standing waves in the MHz frequency range can
      levitate, propel, rotate, align, and assemble metallic microrods (2 MUm long and
      330 nm diameter) in water as well as in solutions of high ionic strength.
      Metallic rods levitated to the midpoint plane of a cylindrical cell when the
      ultrasonic frequency was tuned to create a vertical standing wave. Fast axial
      motion of metallic microrods at ~200 MUm/s was observed at the resonant frequency
      using continuous or pulsed ultrasound. Segmented metal rods (AuRu or AuPt) were
      propelled unidirectionally with one end (Ru or Pt, respectively) consistently
      forward. A self-acoustophoresis mechanism based on the shape asymmetry of the
      metallic rods is proposed to explain this axial propulsion. Metallic rods also
      aligned and self-assembled into long spinning chains, which in the case of
      bimetallic rods had a head-to-tail alternating structure. These chains formed
      ring or streak patterns in the levitation plane. The diameter or distance between
      streaks was roughly half the wavelength of the ultrasonic excitation. The
      ultrasonically driven movement of metallic rods was insensitive to the addition
      of salt to the solution, opening the possibility of driving and controlling
      metallic micromotors in biologically relevant media using ultrasound.

PMID- 22631223
TI  - Aconite poisoning over 5 years: a case series in Hong Kong and lessons towards
      herbal safety.
AB  - BACKGROUND: Aconite poisoning is a severe, life-threatening poisoning related to
      the use of traditional Chinese medicine (TCM). Despite current legislation,
      repeated poisoning cases are steadily encountered. OBJECTIVE: The aim of the
      study was to summarize the clinical features and to elucidate the causative and
      contributory factors leading to aconite poisoning. METHODS: This study was
      conducted within the Hospital Authority Toxicology Reference Laboratory, which is
      the sole tertiary referral clinical toxicology laboratory in Hong Kong. This
      retrospective study reviewed all confirmed aconite poisoning cases handled by a
      clinical toxicology laboratory between April 2004 and July 2009. The diagnosis in
      all cases was confirmed biochemically by detecting aconitum alkaloids in urine
      specimens. Additionally, herbal specimens were morphologically identified and
      herbal formulae were studied and transcribed. The cause of poisoning for each
      case was determined whenever possible. RESULTS: Fifty-two cases were examined in
      this aconite poisoning case series. Neurological, cardiovascular and
      gastrointestinal toxicities were encountered in 49 (94.2%), 46 (88.5%) and 31
      (59.6%) patients, respectively. The poisoning was severe in 6 (11.5%) patients,
      moderate in 17 (32.7%) patients and mild in 29 (55.8%) patients. Amongst 44
      patients (84.6%) in whom the underlying reasons of poisoning could be determined,
      four major causes were found. These included overdose - prescription of a higher
      than recommended dosage of aconite herbs in 17 (32.7%) cases; 'hidden' poisoning
      (the aconite herb was not prescribed but dispensed inadvertently) in 17 (32.7%)
      cases; usage of inadequately processed herbs in 7 (13.5%) cases; and dispensary
      error in 2 (3.9%) cases. No case fatality was recorded. CONCLUSION: In the
      majority of cases in this series, the causes of poisoning can be traced to poor
      quality herbs, poor quality of prescription practice, or dispensary errors. The
      quality issues of TCM practice should be critically addressed to minimize this
      poisoning threat.

PMID- 22631224
TI  - Spontaneous tumor rupture and surgical prognosis of patients with hepatocellular
      carcinoma.
AB  - BACKGROUND: Spontaneous rupture is an uncommon but the most fatal complication of
      hepatocellular carcinoma (HCC) and is recognized as a risk factor for tumor
      recurrence. The present study is to investigate the short- and long-term survival
      of the patients with HCC rupture and evaluate the influence of tumor rupture on
      patient's survival after hepatic resection. PATIENTS AND METHODS: The clinical
      data of 101 patients with HCC rupture from 2000 to 2010 were reviewed
      retrospectively. The management of tumor rupture and clinicopathological
      parameters affecting 30-day mortality of the patients were recorded and
      evaluated. Long-term survival of the 41 patients undergoing hepatic resection was
      compared with 446 patients with non-ruptured HCC at the same time period.
      RESULTS: The 30-day mortality rate of the 101 patients with HCC rupture was 35.6%
      and median survival was 79 days. The independent risk factors affecting 30-day
      mortality were tumor size and blood transfusion quantity. Compared with 446 non
      ruptured HCC patients, 41 patients with ruptured HCC undergoing hepatic resection
      had a similar overall and disease-free survival to 446 without rupture (Log-rank
      test, p = 0.704 and 0.084, respectively). Multivariate analysis revealed that
      age, gender, and tumor size were independently significant factors in
      differentiating tumor rupture from non-rupture. CONCLUSION: Early mortality of
      spontaneous rupture of HCC was dependent on preoperational liver function, tumor
      status, and severity of bleeding. Prolonged survival can be achieved in patients
      with ruptured HCC after hepatic resection as those without the complication.

PMID- 22631225
TI  - Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent
      manner but broadly stimulates nuclear factor kappa B.
AB  - BACKGROUND: Although the peptidyl-prolyl isomerase, cyclophilin-A (peptidyl
      prolyl isomerase, PPIA), has been studied for decades in the context of its
      intracellular functions, its extracellular roles as a major contributor to both
      inflammation and multiple cancers have more recently emerged. A wide range of
      activities have been ascribed to extracellular PPIA that include induction of
      cytokine and matrix metalloproteinase (MMP) secretion, which potentially underlie
      its roles in inflammation and tumorigenesis. However, there have been conflicting
      reports as to which particular signaling events are under extracellular PPIA
      regulation, which may be due to either cell-dependent responses and/or the use of
      commercial preparations recently shown to be highly impure. METHODS: We have
      produced and validated the purity of recombinant PPIA in order to subject it to a
      comparative analysis between different cell types. Specifically, we have used a
      combination of multiple methods such as luciferase reporter screens,
      translocation assays, phosphorylation assays, and nuclear magnetic resonance to
      compare extracellular PPIA activities in several different cell lines that
      included epithelial and monocytic cells. RESULTS: Our findings have revealed that
      extracellular PPIA activity is cell type-dependent and that PPIA signals via
      multiple cellular receptors beyond the single transmembrane receptor previously
      identified, Extracellular Matrix MetalloPRoteinase Inducer (EMMPRIN). Finally,
      while our studies provide important insight into the cell-specific responses,
      they also indicate that there are consistent responses such as nuclear factor
      kappa B (NFkappaB) signaling induced in all cell lines tested. CONCLUSIONS: We
      conclude that although extracellular PPIA activates several common pathways, it
      also targets different receptors in different cell types, resulting in a complex,
      integrated signaling network that is cell type-specific.

PMID- 22631226
TI  - Effect of calcitonin gene-related peptide on osteoblast differentiation in an
      osteoblast and endothelial cell co-culture system.
AB  - We have investigated the in vitro effects and regulatory mechanism of CGRP
      (calcitonin gene-related peptide) on the differentiation of OB (osteoblasts) in
      co-culture with HUVEC (human umbilical vein endothelial cells). Primary human MOB
      (mandibular OB) and OB-like cells (MG-63) were either cultured directly or
      indirectly co-cultured with HUVEC at a 1:1 ratio. Expression of OC (osteocalcin)
      was measured by ELISA, and expression of ALP (alkaline phosphatase) and collagen
      mRNA was measured by quantitative fluorescent PCR. For mineralization nodus, OB
      were stained with Alizarin Red-S. When co-cultured with HUVEC, expression of OC
      and ALP mRNA were increased in MG-63 (P<0.01), and the expression of OC, ALP and
      collagen mRNA were increased in MOB (P<0.01 or 0.05). When treated with CGRP, OC
      and ALP mRNA and mineralization nodus numbers were increased in the MG-63 co
      culture system (P<0.01 or 0.05); OC, ALP and collagen mRNA, and mineralization
      nodus numbers were increased in the MOB co-culture system (P<0.01 or 0.05). The
      effect of CGRP regulation on the differentiation of OB is not only direct but
      also indirect, via its effect on HUVEC and stimulation of OB.

PMID- 22631227
TI  - Fetal bronchoscopy: its successful use in a case of extralobar pulmonary
      sequestration.
AB  - OBJECTIVE: To report the performance of fetal bronchoscopy in a case of pulmonary
      sequestration. MATERIALS AND METHODS: A 24 year-old female, Gravida 2, Para 1,
      was referred at 27.5 weeks with a large fetal left lung mass with marked right
      mediastinal shift and no visible normal left lung. Differential diagnosis
      included possible bronchial atresia. RESULTS: The patient underwent fetal
      laryngoscopy and fetal bronchoscopy at 31.5 weeks. The right lung and a portion
      of the left lung expanded during surgery as a result of bronchial lavage.
      Bronchial atresia or bronchogenic cyst were not found. Pregnancy continued
      uneventfully, with continuous growth of the right lung and a small amount of left
      lung. The patient delivered vaginally at term. The baby underwent thoracoscopic
      resection of a pulmonary sequestration at 10.5 months of age and did well.
      CONCLUSION: Fetal bronchoscopy is feasible. The procedure may prove useful in the
      differential diagnosis and in the potential treatment of different fetal lung
      lesions, as well as aid in the understanding of the role of bronchial obstruction
      as a common pathophysiologic mechanism for different fetal lung masses. Risks and
      benefits of fetal bronchoscopy warrant further experience.

PMID- 22631228
TI  - Enhancing protein stability with retained biological function in transgenic
      plants.
AB  - The final expression level of a transgene-derived protein in transgenic plants
      depends on transcriptional and post-transcriptional processes. Here, we focus on
      methods to improve protein stability without comprising biological function. We
      found that the four isoforms of the Arabidopsis RAD23 protein family are
      relatively stable. The UBA2 domain derived from RAD23a can be used as a portable
      stabilizing signal to prolong the half-life of two unstable transcription factors
      (TFs), HFR1 and PIF3. The increased stability of the TF-UBA2 fusion proteins
      results in an enhanced phenotype in transgenic plants compared to expression of
      the TF alone. Similar results were obtained for the RAD23a UBA1 domain. In
      addition to UBA1/2 of RAD23a, the UBA domain from the Arabidopsis DDI1 protein
      also increased the half-life of the unstable protein JAZ10.1, which is involved
      in jasmonate signaling. Taken together, our results suggest that UBA fusions can
      be used to increase the stability of unstable proteins for basic plant biology
      research as well as crop improvement.

PMID- 22631427
TI  - Regulation of cell death and survival pathways in secondary degeneration of the
      optic nerve - a long-term study.
AB  - PURPOSE: To investigate cell death and survival pathways in secondary
      degeneration of the optic nerve (ON) and retina over a period of 6 months.
      METHODS: A partial transection model of the ON that morphologically separates
      primary and secondary degeneration was applied unilaterally in 89 Wistar rat
      eyes. The upper third of the retinas were analyzed for primary degeneration,
      while the lower third of the retinas were analyzed for secondary degeneration.
      The involvement of members of the mitogen-activated protein (MAP) kinase pathway
      and the PI-3-kinase/Akt pathway were evaluated in primary and secondary
      degeneration in multiple time points over a period of 6 months using
      immunohistochemistry and western blotting. Results were compared to corresponding
      areas from control fellow eyes. RESULTS: All investigated members of the MAP
      kinase pathway were significantly activated in primary degeneration, secondary
      degeneration or both. P-SAPK/JNK and P-ERK were activated in primary degeneration
      without a concomitant activation in secondary degeneration. The prosurvival
      protein p-Akt, a member of the PI-3-kinase survival pathway, was significantly
      activated in secondary but not in primary degeneration. P-c-jun and p-ATF were
      significantly activated in both primary and secondary degeneration. The time
      dependent pattern of activation was different for each protein and in secondary
      degeneration the activation of these proteins was usually short termed.
      CONCLUSIONS: The significant involvement of the MAP kinase pathway and the PI-3
      kinase survival pathway in secondary degeneration of the ON and retina is short
      termed despite continuous retinal ganglion cells (RGCs)apoptosis for at least 6
      months.

PMID- 22631428
TI  - PON gene polymorphisms and ischaemic stroke: a systematic review and meta
      analysis.
AB  - BACKGROUND: Paraoxonase is known to play an important role in the pathophysiology
      of atherosclerosis. Genetic variants of the paraoxonase gene have been implicated
      as risk factors for atherosclerotic diseases such as coronary artery disease, but
      individual genetic association studies examining the relationship between the
      paraoxonase gene polymorphisms and ischaemic stroke have yielded inconsistent
      results. AIM: This study aimed to evaluate the association between the
      paraoxonase gene variants and ischaemic stroke using systematic review with meta
      analysis. METHODS: Relevant studies were identified by searching English and
      Chinese databases extensively. Allele and genotype frequencies for each included
      study were extracted. The odds ratio was calculated using a random-effects or
      fixed-effects model. A Q statistic was used to evaluate homogeneity, and Egger's
      test and funnel plot were used to assess publication bias. RESULTS: A total of 28
      studies were included and identified for the current meta-analysis. It was found
      that the R allele or RR genotype of paraoxonase 1 Q192R polymorphism had an
      increased risk for ischaemic stroke in the general population (192R allele: odds
      ratio: 1.21, 95% confidence interval: 1.08-1.35, P = 0.0009 and 192RR genotype:
      odds ratio: 1.25, 95% confidence interval: 1.06-1.49, P = 0.009 in general
      population, respectively), but there was no significant association between other
      genetic variants of paraoxonase gene and ischaemic stroke. CONCLUSIONS: Existing
      evidence indicates that the Q192R polymorphism (the R allele and RR genotype) is
      associated with an increased risk of ischaemic stroke in the general population.
      Future studies with larger sample sizes will be necessary to confirm the present
      results.

PMID- 22631431
TI  - Biological Macromolecular Dynamics.

PMID- 22631432
TI  - Structure, Motion, Interaction and Expression of Biological Macromolecules.

PMID- 22631434
TI  - Stamping transfer of a quantum dot interlayer for organic photovoltaic cells.
AB  - An organophilic cadmium selenide (CdSe) quantum dot (QD) interlayer was prepared
      on the active layer in organic solar cells by a stamping transfer method. The
      mother substrate composed of a UV-cured film on a polycarbonate film with strong
      solvent resistance makes it possible to spin-coat QDs on it and dry transfer onto
      an active layer without damaging the active layer. The QD interlayers have been
      optimized by controlling the concentration of the QD solution. The coverage of QD
      particles on the active layer was verified by TEM analysis and fluorescence
      images. After insertion of the QD interlayer between the active layer and metal
      cathode, the photovoltaic performances of the organic solar cell were clearly
      enhanced. By ultraviolet photoelectron spectroscopy of CdSe QDs, it can be
      anticipated that the CdSe QD interlayer reduces charge recombination by blocking
      the holes moving to the cathode from the active layer and facilitating efficient
      collection of the electrons from the active layer to the cathode.

PMID- 22631435
TI  - Fostering excellence: development of a course to prepare graduate students for
      research on migration and health.
AB  - Canada is an immigrant-receiving nation and many graduate students in nursing and
      other disciplines pursue immigrant health research. As these students often start
      with inadequate understanding of the policy, theoretical, and research contexts
      in which their work should be situated, we became concerned that the theses and
      dissertations were less sophisticated than were both possible and desirable. This
      led to development of a PhD-level course titled Migration and Health in the
      Canadian Context. In this study, we provide an analytic overview including course
      description, objectives, assignments, and specific class topics. Areas of focus
      include historical and theoretical considerations; determinants of immigrant
      health; refugee health; cultural competence and cultural safety; research
      challenges, approaches, and skills; policy-relevant research; and educational
      imperatives in the health and related disciplines. Salient research is introduced
      in each of these classes. While Canada is the main focus, comparative data are
      provided and there is relevance for nurse-researchers in other immigrant
      receiving countries. 

PMID- 22631436
TI  - Efficacy of transcranial direct current stimulation and repetitive transcranial
      magnetic stimulation for treating fibromyalgia syndrome: a systematic review.
AB  - OBJECTIVE:  To systematically review the literature to date applying repetitive
      transcranial magnetic stimulation (rTMS) or transcranial direct current
      stimulation (tDCS) for patients with fibromyalgia syndrome (FMS). METHOD: 
      Electronic bibliography databases screened included PubMed, Ovid MEDLINE,
      PsychINFO, CINAHL, and Cochrane Library. The keyword "fibromyalgia" was combined
      with ("transcranial" and "stimulation") or "TMS" or "tDCS" or "transcranial
      magnetic stimulation" or "transcranial direct current stimulation". RESULTS: 
      Nine of 23 studies were included; brain stimulation sites comprised either the
      primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC). Five
      studies used rTMS (high-frequency-M1: 2, low-frequency-DLPFC: 2, high-frequency
      DLPFC: 1), while 4 applied tDCS (anodal-M1: 1, anodal-M1/DLPFC: 3). Eight were
      double-blinded, randomized controlled trials. Most (80%) rTMS studies that
      measured pain reported significant decreases, while all (100%) tDCS studies with
      pain measures reported significant decreases. Greater longevity of significant
      pain reductions was observed for excitatory M1 rTMS/tDCS. CONCLUSION:  Studies
      involving excitatory rTMS/tDCS at M1 showed analogous pain reductions as well as
      considerably fewer side effects compared to FDA apaproved FMS pharmaceuticals.
      The most commonly reported side effects were mild, including transient headaches
      and scalp discomforts at the stimulation site. Yearly use of rTMS/tDCS regimens
      appears costly ($11,740 to 14,507/year); however, analyses to apapropriately
      weigh these costs against clinical and quality of life benefits for patients with
      FMS are lacking. Consequently, rTMS/tDCS should be considered when treating
      patients with FMS, particularly those who are unable to find adequate symptom
      relief with other therapies. Further work into optimal stimulation parameters and
      standardized outcome measures is needed to clarify associated efficacy and
      effectiveness.

PMID- 22631437
TI  - Genome-scale metabolic model of the fission yeast Schizosaccharomyces pombe and
      the reconciliation of in silico/in vivo mutant growth.
AB  - BACKGROUND: Over the last decade, the genome-scale metabolic models have been
      playing increasingly important roles in elucidating metabolic characteristics of
      biological systems for a wide range of applications including, but not limited
      to, system-wide identification of drug targets and production of high value
      biochemical compounds. However, these genome-scale metabolic models must be able
      to first predict known in vivo phenotypes before it is applied towards these
      applications with high confidence. One benchmark for measuring the in silico
      capability in predicting in vivo phenotypes is the use of single-gene mutant
      libraries to measure the accuracy of knockout simulations in predicting mutant
      growth phenotypes. RESULTS: Here we employed a systematic and iterative process,
      designated as Reconciling In silico/in vivo mutaNt Growth (RING), to settle
      discrepancies between in silico prediction and in vivo observations to a newly
      reconstructed genome-scale metabolic model of the fission yeast,
      Schizosaccharomyces pombe, SpoMBEL1693. The predictive capabilities of the genome
      scale metabolic model in predicting single-gene mutant growth phenotypes were
      measured against the single-gene mutant library of S. pombe. The use of RING
      resulted in improving the overall predictive capability of SpoMBEL1693 by 21.5%,
      from 61.2% to 82.7% (92.5% of the negative predictions matched the observed
      growth phenotype and 79.7% the positive predictions matched the observed growth
      phenotype). CONCLUSION: This study presents validation and refinement of a newly
      reconstructed metabolic model of the yeast S. pombe, through improving the
      metabolic model's predictive capabilities by reconciling the in silico predicted
      growth phenotypes of single-gene knockout mutants, with experimental in vivo
      growth data.

PMID- 22631439
TI  - Can apolipoproteins and complement factors be biomarkers of Alzheimer's disease?
AB  - Alzheimer's disease is the most common cause of dementia in elderly persons.
      Quick diagnosis of Alzheimer's disease will allow treatments that may help slow
      its progression. The correlation between cerebrospinal fluid (CSF) parameters and
      progression of Alzheimer's disease is higher than and independent of other risk
      factors. We have compared sixteen CSF samples of clinically diagnosed Alzheimer's
      disease patients with non demented subjects using proteomics approach.
      Apolipoprotein E, apolipoprotein J, complement C4b, hemopexin and complement
      factor B were identified as differentially expressed proteins. Pathway analyses
      show that these proteins have interacting partners in Alzheimer's and apoptotic
      pathways. The possible roles of these proteins in relation to the disease are
      discussed.

PMID- 22631438
TI  - Role of apolipoprotein A-II in the structure and remodeling of human high-density
      lipoprotein (HDL): protein conformational ensemble on HDL.
AB  - High-density lipoproteins (HDL, or "good cholesterol") are heterogeneous
      nanoparticles that remove excess cell cholesterol and protect against
      atherosclerosis. The cardioprotective action of HDL and its major protein,
      apolipoprotein A-I (apoA-I), is well-established, yet the function of the second
      major protein, apolipoprotein A-II (apoA-II), is less clear. In this review, we
      postulate an ensemble of apolipoprotein conformations on various HDL. This
      ensemble is based on the crystal structure of Delta(185-243)apoA-I determined by
      Mei and Atkinson combined with the "double-hairpin" conformation of apoA
      II(dimer) proposed in the cross-linking studies by Silva's team, and is supported
      by the wide array of low-resolution structural, biophysical, and biochemical data
      obtained by many teams over decades. The proposed conformational ensemble helps
      integrate and improve several existing HDL models, including the "buckle-belt"
      conformation of apoA-I on the midsize disks and the "trefoil/tetrafoil"
      arrangement on spherical HDL. This ensemble prompts us to hypothesize that
      endogenous apoA-II (i) helps confer lipid surface curvature during conversion of
      nascent discoidal HDL(A-I) and HDL(A-II) containing either apoA-I or apoA-II to
      mature spherical HDL(A-I/A-II) containing both proteins, and (ii) hinders
      remodeling of HDL(A-I/A-II) by hindering the expansion of the apoA-I
      conformation. Also, we report that, although endogenous apoA-II circulates mainly
      on the midsize spherical HDL(A-I/A-II), exogenous apoA-II can bind to HDL of any
      size, thereby slightly increasing this size and stabilizing the HDL assembly.
      This suggests distinctly different effects of the endogenous and exogenous apoA
      II on HDL. Taken together, the existing results and models prompt us to postulate
      a new structural and functional role of apoA-II on human HDL.

PMID- 22631440
TI  - Amyloid-beta peptide 1-42 causes microtubule deregulation through N-methyl-D
      aspartate receptors in mature hippocampal cultures.
AB  - Alzheimer's disease (AD) is the most common age-related neurodegenerative
      disorder among the elderly. Nmethyl- D-aspartate receptor (NMDAR) overactivation
      has been implicated in early synaptic dysfunction that precedes late
      neurodegeneration in AD. Moreover, oligomers of amyloid-beta peptide (Abeta) 1-42
      are considered the most synaptotoxic forms, responsible for early cognitive
      deficits in AD. In this work we evaluate the role of NMDARs on Abeta-evoked
      neuronal dysfunction and cell death through changes in microtubule polymerization
      in mature hippocampal cultures. Exposure to Abeta 1-42 caused a decrease in total
      and polymerized levels of beta-III tubulin and polymerized alpha-tubulin,
      suggesting microtubule disassembly. Moreover, Abeta induced DNA fragmentation in
      both neuronal and non-neuronal cells. Indeed, the effects of Abeta on beta-III
      tubulin polymerization were significantly correlated with reduced neurite length
      and neuronal DNA fragmentation. Interestingly, these effects were prevented by MK
      801 and memantine, suggesting a role for extrasynaptic NMDARs in Abeta toxicity,
      and by ifenprodil, further indicating the involvement of GluN2B-containing
      NMDARs. Nevertheless, exposure to Abeta did not potentiate the effects caused by
      selective activation of NMDARs. Data largely suggest that Abeta-induced
      hippocampal neuronal dysfunction occurs through NMDAR-dependent microtubule
      disassembly associated to neurite retraction and DNA fragmentation in mature
      hippocampal cells.

PMID- 22631441
TI  - Alzheimer's disease amyloid peptides interact with DNA, as proved by surface
      plasmon resonance.
AB  - According to the amyloid hypothesis, abnormal processing of the beta-amyloid
      precursor protein in Alzheimer's disease patients increases the production of
      beta-amyloid toxic peptides, which, after forming highly aggregated fibrillar
      structures, lead to extracellular plaques formation, neuronal loss and dementia.
      However, a great deal of evidence has point to intracellular small oligomers of
      amyloid peptides, probably transient intermediates in the process of fibrillar
      structures formation, as the most toxic species. In order to study the amyloid
      DNA interaction, we have selected here three different forms of the amyloid
      peptide: Abeta1-40, Abeta25-35 and a scrambled form of Abeta25-35. Surface
      Plasmon Resonance was used together with UV-visible spectroscopy, Electrophoresis
      and Electronic Microscopy to carry out this study. Our results prove that,
      similarly to the full length Abeta1-42, all conformations of toxic amyloid
      peptides, Abeta1-40 and Abeta25-35, may bind DNA. In contrast, the scrambled form
      of Abeta25-35, a non-aggregating and nontoxic form of this peptide, could not
      bind DNA. We conclude that although the amyloid-DNA interaction is closely
      related to the amyloid aggregation proneness, this cannot be the only factor
      which determines the interaction, since small oligomers of amyloid peptides may
      also bind DNA if their predominant negatively charged amino acid residues are
      previously neutralized.

PMID- 22631442
TI  - Practical lessons from amyloid immunotherapy trials in Alzheimer disease.
AB  - OBJECTIVES: Amyloid immunotherapy trials are central in Alzheimer disease (AD)
      drug development, with the potential to influence all future disease-modifying
      randomized controlled trials (RCTs). This study investigates practical
      experiences of staff and participants in immunotherapy RCTs. SETTING AND METHODS:
      The Clinical Trial Research Unit of the Memory Clinic at Karolinska University
      Hospital, Sweden is an experienced centre specialized in Alzheimer RCTs, where
      four active and passive phase I/II immunotherapy trials are currently ongoing.
      Meetings were held with staff members, who were asked to describe their
      experiences and suggest necessary improvements. In addition, a pilot study was
      conducted to investigate motivations and expectations of participants in
      immunotherapy RCTs. A questionnaire was sent to 20 patients, and another similar
      questionnaire to their caregivers. RESULTS: The main issues emphasized by staff
      members concerned the critical window of opportunity for recruiting RCTs
      participants, the much higher level of effort required of patients and caregivers
      in immunotherapy RCTs compared to classical cholinesterase inhibitor RCTs,
      problematic informed consent procedures, and confidentiality limitations in
      trials with different sponsors. For patients and caregivers, the main reason for
      participating in RCTs was the wish to help research and other people, followed by
      the need for information, continuity of care, safety and support. Compared to
      patients, caregivers' expectations of trial results were more realistic.
      CONCLUSIONS: More open debates of practical experiences from different trial
      centres and sponsors are essential for optimizing trial designs and improving
      conditions for participants.

PMID- 22631443
TI  - Identical but different: haemophilia B in monozygotic twins with inhibitor in one
      brother and subsequent successful immune tolerance induction.

PMID- 22631444
TI  - Clinical outcome after insemination with donor sperm in patients with poor
      results in ICSI cycles.
AB  - The introduction of intracytoplasmic sperm injection (ICSI) provided an effective
      treatment for infertile couples whose infertility was attributed to male factors.
      However, some of them face poor results after ICSI and subsequently use
      artificial insemination with donor sperm (AID). Only a few studies have reported
      on the clinical outcome of AID cycles after previous failed ICSI cycles, with
      contrasting results. The results reported here involve a cohort of 47 couples
      undertaking 175 AID cycles after 120 failed ICSI cycles for various reasons.
      Couples were allocated to two groups according to the availability of top quality
      embryos (TQE) in ICSI cycles. In our series, AID was successful for couples with
      and without TQE previously transferred in ICSI cycles, the live birth rate (LBR)
      per cycle being 20.0% and 13.3%, respectively. However, couples with TQE tended
      to succeed more rapidly than couples with poor quality embryos, with a higher
      cumulative LBR (68.0% versus 54.5%, respectively). These findings demonstrate
      that even couples with a history of unsuccessful ICSI cycles because of poor
      embryo quality are able to achieve high LBR after AID cycles. However, such
      couples have a lower cumulative LBR and are required to be more patient to
      achieve parenthood.

PMID- 22631446
TI  - A superacid-catalyzed synthesis of porous membranes based on triazine frameworks
      for CO2 separation.
AB  - A general strategy for the synthesis of porous, fluorescent, triazine-framework
      based membranes with intrinsic porosity through an aromatic nitrile trimerization
      reaction is presented. The essence of this strategy lies in the use of a
      superacid to catalyze the cross-linking reaction efficiently at a low
      temperature, allowing porous polymer membrane architectures to be facilely
      derived. With functionalized triazine units, the membrane exhibits an increased
      selectivity for membrane separation of CO(2) over N(2). The good ideal CO(2)/N(2)
      selectivity of 29 +/- 2 was achieved with a CO(2) permeability of 518 +/- 25
      barrer. Through this general synthesis protocol, a new class of porous polymer
      membranes with tunable functionalities and porosities can be derived,
      significantly expanding the currently limited library of polymers with intrinsic
      microporosity for synthesizing functional membranes in separation, catalysis, and
      energy storage/conversion.

PMID- 22631447
TI  - Error patterns in young German children's wh-questions.
AB  - In this article we report two studies: a detailed longitudinal analysis of errors
      in wh-questions from six German-learning children (age 2 ; 0-3 ; 0) and an
      analysis of the prosodic characteristics of wh-questions in German child-directed
      speech. The results of the first study demonstrate that German-learning children
      frequently omit the initial wh-word. A lexical analysis of wh-less questions
      revealed that children are more likely to omit the wh-word was ('what') than
      other wh-words (e.g. wo 'where'). In the second study, we performed an acoustic
      analysis of sixty wh-questions that one mother produced during her child's third
      year of life. The results show that the wh-word was is much less likely to be
      accented than the wh-word wo, indicating a relationship between children's
      omission of wh-words and the stress patterns associated with wh-questions. The
      findings are discussed in the light of discourse-pragmatic and metrical accounts
      of omission errors.

PMID- 22631448
TI  - Inhibition of UVB-induced oxidative damage and apoptotic biochemical changes in
      human lymphocytes by 2,5-dihydroxy-3-undecyl-1,4-benzoquinone (embelin).
AB  - PURPOSE: The present study investigates the inhibition of Ultraviolet B (UVB, 290
      320 nm) radiation-induced oxidative damage in peripheral blood human lymphocytes
      by embelin extracted from Embelia ribes. MATERIALS AND METHODS: Embelin was
      extracted, purified and characterized. Prior to inhibitory assessment, a maximum
      concentration of embelin that was non-toxic was determined. Six experimental
      groups, including respective controls were made to assess the inhibitory effect
      of embelin for the selected concentrations of 10 and 20 MUg/ml. For the
      experimental groups; lymphocytes (1 * 10(6) cells) were pre-treated with the
      chosen concentration of embelin for a period of 60 min and then exposed to UVB
      for 30 min. UVB radiation inhibitory effect of embelin assessed by measuring
      antioxidant and lipid peroxidation levels, deoxyribonucleic acid (DNA) damage,
      reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) at
      scheduled time points after irradiation. RESULTS: Pre-treatment of lymphocytes
      with embelin prevents UVB-induced oxidative damage. An increase in antioxidant
      levels in irradiated cells in the presence of embelin and UV absorbance of
      embelin could be the reason for the decrease in lipid peroxidation level and
      prevention of DNA damage by UVB radiation. CONCLUSION: Embelin prevents oxidative
      stress induced by UVB irradiation via its antioxidant property.

PMID- 22631449
TI  - Unusual orbital involvement in Erdheim Chester disease: a radiological diagnosis.
AB  - Erdheim-Chester disease (ECD) is an exceedingly rare, disseminated non-Langerhan
      cell histiocytosis with multisystem involvement, having characteristic sclerotic
      skeletal lesions. We present an unusual case primarily manifesting as an
      extensive orbital disease, with low-grade systemic involvement. Owing to its
      rarity and therefore lack of general awareness it remains a difficult clinical
      and pathologic diagnosis. Immuno-histochemistry of the biopsy specimen is
      diagnostic.

PMID- 22631445
TI  - Inflammasome activation of IL-1 family mediators in response to cutaneous
      photodamage.
AB  - Although keratinocytes are relatively resistant to ultraviolet radiation (UVR)
      induced damage, repeated UVR exposure result in accumulated DNA mutations that
      can lead to epidermal malignancies. Keratinocytes play a central role in
      elaborating innate responses that lead to inflammation and influence the
      generation of adaptive immune responses in skin. Apart from the minor cellular
      constituents of the epidermis, specifically Langerhans cells and melanocytes,
      keratinocytes are the major source of cytokines. UVR exposure stimulates
      keratinocytes to secrete abundant pro-inflammatory IL-1-family proteins, IL
      1alpha, IL-1beta, IL-18, and IL-33. Normal skin contains only low levels of
      inactive precursor forms of IL-1beta and IL-18, which require caspase 1-mediated
      proteolysis for their maturation and secretion. However, caspase-1 activation is
      not constitutive, but dependents on the UV-induced formation of an active
      inflammasome complex. IL-1 family cytokines can induce a secondary cascade of
      mediators and cytokines from keratinocytes and other cells resulting in wide
      range of innate processes including infiltration of inflammatory leukocytes,
      induction of immunosuppression, DNA repair or apoptosis. Thus, the ability of
      keratinocytes to produce a wide repertoire of proinflammatory cytokines can
      influence the immune response locally as well as systematically, and alter the
      host response to photodamaged cells. We will highlight differential roles played
      by each IL-1 family molecule generated by UV-damaged keratinocytes, and reveal
      their complementary influences in modulating acute inflammatory and immunological
      events that follow cutaneous UV exposure.

PMID- 22631451
TI  - Graphene nanoribbons as low band gap donor materials for organic photovoltaics:
      quantum chemical aided design.
AB  - Graphene nanoribbons (GNRs) are strips of graphene cut along a specific direction
      that feature peculiar electronic and optical properties owing to lateral
      confinement effects. We show here by means of (time-dependent) density functional
      theory calculations that GNRs with properly designed edge structures fulfill the
      requirements in terms of electronic level alignment with common acceptors
      (namely, C(60)), solar light harvesting, and singlet-triplet exchange energy to
      be used as low band gap semiconductors for organic photovoltaics.

PMID- 22631450
TI  - Correlation between spatial (3D) structure of pea and bean thylakoid membranes
      and arrangement of chlorophyll-protein complexes.
AB  - BACKGROUND: The thylakoid system in plant chloroplasts is organized into two
      distinct domains: grana arranged in stacks of appressed membranes and non
      appressed membranes consisting of stroma thylakoids and margins of granal stacks.
      It is argued that the reason for the development of appressed membranes in plants
      is that their photosynthetic apparatus need to cope with and survive ever
      changing environmental conditions. It is not known however, why different plant
      species have different arrangements of grana within their chloroplasts. It is
      important to elucidate whether a different arrangement and distribution of
      appressed and non-appressed thylakoids in chloroplasts are linked with different
      qualitative and/or quantitative organization of chlorophyll-protein (CP)
      complexes in the thylakoid membranes and whether this arrangement influences the
      photosynthetic efficiency. RESULTS: Our results from TEM and in situ CLSM
      strongly indicate the existence of different arrangements of pea and bean
      thylakoid membranes. In pea, larger appressed thylakoids are regularly arranged
      within chloroplasts as uniformly distributed red fluorescent bodies, while
      irregular appressed thylakoid membranes within bean chloroplasts correspond to
      smaller and less distinguished fluorescent areas in CLSM images. 3D models of pea
      chloroplasts show a distinct spatial separation of stacked thylakoids from
      stromal spaces whereas spatial division of stroma and thylakoid areas in bean
      chloroplasts are more complex. Structural differences influenced the PSII
      photochemistry, however without significant changes in photosynthetic efficiency.
      Qualitative and quantitative analysis of chlorophyll-protein complexes as well as
      spectroscopic investigations indicated a similar proportion between PSI and PSII
      core complexes in pea and bean thylakoids, but higher abundance of LHCII antenna
      in pea ones. Furthermore, distinct differences in size and arrangements of LHCII
      PSII and LHCI-PSI supercomplexes between species are suggested. CONCLUSIONS:
      Based on proteomic and spectroscopic investigations we postulate that the
      differences in the chloroplast structure between the analyzed species are a
      consequence of quantitative proportions between the individual CP complexes and
      its arrangement inside membranes. Such a structure of membranes induced the
      formation of large stacked domains in pea, or smaller heterogeneous regions in
      bean thylakoids. Presented 3D models of chloroplasts showed that stacked areas
      are noticeably irregular with variable thickness, merging with each other and not
      always parallel to each other.

PMID- 22631452
TI  - Intravitreal ranibizumab (lucentis) for the treatment of diabetic macular edema:
      a systematic review and meta-analysis of randomized clinical control trials.
AB  - PURPOSE: To evaluate the therapeutic effect and safety of intravitreal
      ranibizumab (RBZ) or RBZ combined with focal/grid laser in diabetic macular edema
      (DME). DESIGN: Systematic review of randomized clinical control trials (RCCTs)
      comparing RBZ or RBZ combined with focal/grid laser to non-drug control or
      focal/grid laser in DME was performed. METHODS: The RCCTs in Cochrane Central
      Register of Controlled Trials, PUBMED, EMBASE, the metaRegister of Controlled
      Trials, and ClinicalTrials.gov were included. The means and standard deviations
      of change from baseline in best-corrected visual acuity (BCVA) and central
      macular thickness (CMT) were extracted at 12 or 24 months. Data regarding
      complications were collected. The Review Manager 5.1.2 was used. RESULTS: Four
      trials with a total of 1313 DME patients were included. Our analysis showed that
      intravitreal RBZ appeared to be superior to non-drug therapy in reducing CMT (12
      months, p = 0.02), and improving BCVA with statistical significance (12 months, p
      = 0.0003). RBZ combined with focal/grid laser experienced statistically
      significant reduction in CMT (12 months, p = 0.01), and improvement in BCVA (12
      months, p < 0.00001; 24 months, p = 0.007) compared with focal/grid laser. The
      incidence of adverse events (AEs) had no statistical difference between RBZ
      monotherapy or RBZ combined with laser and the noninvasive interventions. The
      improvement in BCVA and CMT from the RBZ and RBZ plus laser arms both had no
      statistically significant difference. While the mean number of intravitreal
      injections needed was lower in RBZ plus laser arm than RBZ arm at the end of 24
      months. CONCLUSIONS: Our analysis shows that RBZ and RBZ combined with focal/grid
      laser is more advantageous than non-drug treatment or focal/grid laser in
      reducing CMT and improving BCVA in DME during 12 and 24 months follow-up period
      and can be well tolerated based on the safety assessment. Intravitreal RBZ may be
      equivalent to RBZ combined with focal/grid laser.

PMID- 22631562
TI  - "I am just thankful": the experience of gratitude following traumatic spinal cord
      injury.
AB  - This study explored the experience of gratitude in everyday life following
      traumatic spinal cord injury (SCI) by applying thematic analysis to personal
      experience narratives. Fifteen participants including two negative cases with SCI
      shared individual experiences of gratitude according to five themes: (a) everyday
      life, (b) family support, (c) new opportunities, (d) positive sense of self, and
      (e) gratitude to God. The findings demonstrated that participants benefited from
      their efforts to appraise challenging life experiences as positive. Therapists
      could apply intentional and guided gratitude interventions so that individuals
      would practice and embrace gratitude in adjusting, coping, and adapting
      positively to various life changes following trauma.

PMID- 22631563
TI  - Characterization of the phosphoproteome of mature Arabidopsis pollen.
AB  - Successful pollination depends on cell-cell communication and rapid cellular
      responses. In Arabidopsis, the pollen grain lands on a dry stigma, where it
      hydrates, germinates and grows a pollen tube that delivers the sperm cells to the
      female gametophyte to effect double fertilization. Various studies have
      emphasized that a mature, dehydrated pollen grain contains all the transcripts
      and proteins required for germination and initial pollen tube growth. Therefore,
      it is important to explore the role of post-translational modifications (here
      phosphorylation), through which many processes induced by pollination are
      probably controlled. We report here a phosphoproteomic study conducted on mature
      Arabidopsis pollen grains with the aim of identifying potential targets of
      phosphorylation. Using three enrichment chromatographies, a broad coverage of
      pollen phosphoproteins with 962 phosphorylated peptides corresponding to 598
      phosphoproteins was obtained. Additionally, 609 confirmed phosphorylation sites
      were successfully mapped. Two hundred and seven of 240 phosphoproteins that were
      absent from the PhosPhAt database containing the empirical Arabidopsis
      phosphoproteome showed highly enriched expression in pollen. Gene ontology (GO)
      enrichment analysis of these 240 phosphoproteins shows an over-representation of
      GO categories crucial for pollen tube growth, suggesting that phosphorylation
      regulates later processes of pollen development. Moreover, motif analyses of
      pollen phosphopeptides showed an over-representation of motifs specific for
      Ca2+/calmodulin-dependent protein kinases, mitogen-activated protein kinases, and
      binding motifs for 14-3-3 proteins. Lastly, one tyrosine phosphorylation site was
      identified, validating the TDY dual phosphorylation motif of mitogen-activated
      protein kinases (MPK8/MPK15). This study provides a solid basis to further
      explore the role of phosphorylation during pollen development.

PMID- 22631565
TI  - 2D SMARTCyp reactivity-based site of metabolism prediction for major drug
      metabolizing cytochrome P450 enzymes.
AB  - Cytochrome P450 (CYP) 3A4, 2D6, 2C9, 2C19, and 1A2 are the most important drug
      metabolizing enzymes in the human liver. Knowledge of which parts of a drug
      molecule are subject to metabolic reactions catalyzed by these enzymes is crucial
      for rational drug design to mitigate ADME/toxicity issues. SMARTCyp, a recently
      developed 2D ligand structure-based method, is able to predict site-specific
      metabolic reactivity of CYP3A4 and CYP2D6 substrates with an accuracy that rivals
      the best and more computationally demanding 3D structure-based methods. In this
      article, the SMARTCyp approach was extended to predict the metabolic hotspots for
      CYP2C9, CYP2C19, and CYP1A2 substrates. This was accomplished by taking into
      account the impact of a key substrate-receptor recognition feature of each enzyme
      as a correction term to the SMARTCyp reactivity. The corrected reactivity was
      then used to rank order the likely sites of CYP-mediated metabolic reactions. For
      60 CYP1A2 substrates, the observed major sites of CYP1A2 catalyzed metabolic
      reactions were among the top-ranked 1, 2, and 3 positions in 67%, 80%, and 83% of
      the cases, respectively. The results were similar to those obtained by MetaSite
      and the reactivity + docking approach. For 70 CYP2C9 substrates, the observed
      sites of CYP2C9 metabolism were among the top-ranked 1, 2, and 3 positions in
      66%, 86%, and 87% of the cases, respectively. These results were better than the
      corresponding results of StarDrop version 5.0, which were 61%, 73%, and 77%,
      respectively. For 36 compounds metabolized by CYP2C19, the observed sites of
      metabolism were found to be among the top-ranked 1, 2, and 3 sites in 78%, 89%,
      and 94% of the cases, respectively. The computational procedure was implemented
      as an extension to the program SMARTCyp 2.0. With the extension, the program can
      now predict the site of metabolism for all five major drug-metabolizing enzymes
      with an accuracy similar to or better than that achieved by the best 3D structure
      based methods. Both the Java source code and the binary executable of the program
      are freely available to interested users.

PMID- 22631564
TI  - Efficacy of fixed-dose combination artesunate-amodiaquine versus artemether
      lumefantrine for uncomplicated childhood Plasmodium falciparum malaria in
      Democratic Republic of Congo: a randomized non-inferiority trial.
AB  - BACKGROUND: In 2005, the Democratic Republic of Congo (DRC) adopted artesunate
      and amodiaquine (ASAQ) as first-line anti-malarial treatment. In order to compare
      the efficacy of the fixed-dose formulation ASAQ versus artemether-lumefantrine
      (AL), a randomized, non-inferiority open-label trial was conducted in Katanga.
      METHODS: Children aged six and 59 months with uncomplicated Plasmodium falciparum
      malaria were enrolled and randomly allocated into one of the two regimens. The
      risk of recurrent parasitaemia by day 42, both unadjusted and adjusted by PCR
      genotyping to distinguish recrudescence from new infection, was analysed.
      RESULTS: Between April 2008 and March 2009, 301 children were included: 156 with
      ASAQ and 145 with AL. No early treatment failures were reported. Among the 256
      patients followed-up at day 42, 32 patients developed late clinical or
      parasitological failure (9.9% (13/131) in the ASAQ group and 15.2% (19/125) in
      the AL group). After PCR correction, cure rates were 98.3% (95%CI, 94.1-99.8) in
      the ASAQ group and 99.1% (95%CI, 94.9-99.9) in the AL group (difference -0.7%,
      one sided 95% CI -3.1). Kaplan-Meier PCR-adjusted cure rates were similar. Both
      treatment regimens were generally well tolerated. CONCLUSION: Both ASAQ and AL
      are highly effective and currently adequate as the first-line treatment of
      uncomplicated falciparum malaria in this area of Katanga, DRC. However, in a very
      large country, such as DRC, and because of possible emergence of resistance from
      other endemic regions, surveillance of efficacy of artemisinin-based combination
      treatments, including other evaluations of the resistance of ASAQ, need to be
      done in other provinces. TRIAL REGISTRATION: The protocol was registered with the
      clinicaltrials.gov, open clinical trial registry under the identifier number
      NCT01567423.

PMID- 22631566
TI  - Survey of the management of acute pancreatitis in surgical departments in Sweden.
AB  - OBJECTIVE: Several international guidelines concerning the treatment of acute
      pancreatitis has been published during the last decades. However, Scandinavian
      guidelines are still lacking. The aim of the present study is to identify current
      treatment strategies for acute pancreatitis in Sweden and to evaluate if there is
      a need for improvement and the role of guidelines. MATERIAL AND METHODS: A
      questionnaire was e-mailed to the surgical departments at all Swedish hospitals
      (n = 58) managing patients with acute pancreatitis. Comparisons were made both
      between university and non-university hospitals, and between hospitals with more
      versus less than 150,000 persons in the primary catchment population. RESULTS:
      Fifty-one hospitals responded (88%). In median, 65 (12-200) patients with acute
      pancreatitis are treated yearly at each hospital. Of 51 hospitals, 18 perform a
      severity classification, with APACHE II being the most commonly used. A majority
      are of the opinion that a scoring system is not better than the judgment of a
      senior consultant. In severe acute pancreatitis, 29/48 routinely administer
      antibiotics, 29/48 use enteral nutrition, and 25/49 have a standardized follow-up
      plan. The majority considered administration of intravenous fluids as the most
      important treatment in severe acute pancreatitis. After mild gallstone-induced
      acute pancreatitis, the corresponding response was cholecystectomy, especially at
      larger hospitals (p = 0.002). Of 47, 42 are interested in developing a
      Scandinavian quality register. CONCLUSIONS: The results from this first Swedish
      national survey provide an insight into current traditions of treatment of acute
      pancreatitis and points, for example, at the lack of early severity
      stratification. A majority of hospitals are interested in developing a quality
      register in acute pancreatitis.

PMID- 22631567
TI  - Rate, associated factors and outcomes of recurrence of Kawasaki disease in
      Ontario, Canada.
AB  - BACKGROUND: Previous studies on recurrence of Kawasaki disease (KD) have mostly
      been limited to Japan, which has an incidence of KD 8-10-fold higher than North
      America. The aim of the present study was to determine the rate of KD recurrence
      for patients in Ontario, to identify factors potentially associated with
      increased odds of recurrence, and to compare the clinical course and outcomes of
      index and recurrent KD episodes. METHODS: Review was undertaken of all patients
      with recurrence of KD identified in Ontario, Canada, from 1995 to 2006. All
      patients with recurrence of KD (defined as at least three clinical signs of KD in
      addition to fever >= 5 days), presenting >= 14 days after the return to baseline
      from the index episode were included. RESULTS: A total of 1010 patients were
      followed for 5786 patient-years. During this period a total of 17 recurrent
      episodes in 16 patients were identified at a median of 1.5 years after the
      initial episode (2 weeks-5 years). Rate of recurrence of KD was 2.9 episodes/1000
      patient-years, which is higher than the expected annual incidence of KD in the
      same age group (26.2/100,000 per year). No factors associated with increased risk
      of recurrence were identified, perhaps due to the small number of events.
      Clinical course and outcomes of the index and recurrent KD episodes were similar.
      CONCLUSIONS: A previous history of KD should increase the index of suspicion for
      future episodes of KD to allow for rapid recognition, treatment and to achieve
      optimal outcomes.

PMID- 22631568
TI  - Adams-Oliver syndrome and familial MYH9 mutation.

PMID- 22631569
TI  - White-matter damage in a neonate with disseminated herpes simplex virus
      infection.

PMID- 22631570
TI  - Neonatal transient distal renal tubular acidosis in a patient with
      pseudohypoparathyroidism type 1a.

PMID- 22631571
TI  - Use of fibrin glue in the treatment of pneumothorax in premature infant.

PMID- 22631572
TI  - Balloon-occluded retrograde transvenous obliteration for congenital portosystemic
      venous shunt: report of two cases.

PMID- 22631573
TI  - Pediatric idiopathic TTP diagnosed with decreased ADAMTS13 activity.

PMID- 22631574
TI  - Fulminant Clostridium perfringens sepsis during induction chemotherapy in
      childhood leukemia.

PMID- 22631575
TI  - Cystic adult-type granulosa cell tumor in a 7-year-old girl with precocious
      pseudopuberty.

PMID- 22631576
TI  - Successful treatment for hepatoblastoma in a 1-year-old boy with trisomy 18.

PMID- 22631577
TI  - Shaking-related child abuse: vigorous shaking of pram.

PMID- 22631578
TI  - 45,X/46,XX/47,XXX mosaicism.

PMID- 22631579
TI  - Iliopsoas abscess in the neonate with immunodeficiency.

PMID- 22631580
TI  - Persistent posterior pneumomediastinum in a neonate.

PMID- 22631581
TI  - 3beta-Hydroxy-Delta5 -C27 -steroid dehydrogenase/isomerase deficiency in a
      patient who underwent oral bile acid therapy for 10 years and delivered two
      healthy infants: reply.

PMID- 22631582
TI  - Management of acute myocardial dysfunction with disturbed consciousness due to
      Kawasaki disease.

PMID- 22631583
TI  - Does early hyperbaric oxygen therapy prevent extremity necrosis in Nicolau
      syndrome?

PMID- 22631584
TI  - Imerslund-Grasbeck syndrome: new mutation in amnionless.

PMID- 22631585
TI  - Hand-foot-genital syndrome with a 7p15 deletion: clinically recognizable
      syndrome.

PMID- 22631586
TI  - Ganglioneuroblastoma, intermixed with opsoclonus-myoclonus syndrome.

PMID- 22631587
TI  - Calf pain: atypical presentation of acute lymphoblastic leukemia mimicking deep
      venous thrombosis.

PMID- 22631588
TI  - Immunoglobulin resistance in Kawasaki disease with chronic granulomatous disease.

PMID- 22631589
TI  - Complex regional pain syndrome by vaccination: a case of complex regional pain
      syndrome after vaccination of influenza A(H1N1).

PMID- 22631590
TI  - Thymic abscess and bacteremia caused by methicillin-susceptible Staphylococcus
      aureus in a child.

PMID- 22631591
TI  - Intraluminal tracheal occlusion using a modified 8-mm Z-stent in a sheep model of
      left-sided congenital diaphragmatic hernia.
AB  - OBJECTIVE: To evaluate pulmonary growth and development after fetoscopic
      intraluminal tracheal occlusion (FITO) using a modified 8-mm Z-stent in an ovine
      model of congenital left-sided diaphragmatic hernia (CDH). METHODS: Thirty-three
      time-dated ewes were studied: Group I: healthy controls; Group II: CDH controls
      (untreated); Group III: CDH treated with FITO. CDH was created in Groups II and
      III at 70-80 days' gestation. FITO was performed at 100-110 days. Left lung
      histological, morphometric, immunohistochemical and biochemical studies were
      conducted after delivery and euthanasia at 138 days. RESULTS: Fifteen (45%)
      animals (Group I: 3; Group II: 5; Group III: 7) were available for analysis. The
      left lung parenchymal volume to fetal weight ratios were similar between Groups I
      and III (p = 0.24), and higher than Group II (p < 0.05III (79 versus 75%, p =
      0.26), compared to 41% in Group II (p < 0.05). Pulmonary hypoplasia occurred in
      1/7 (16%) in the FITO group, compared to 100% in Group II and 0% in Group I (p =
      .003). DNA and protein were significantly increased in Group III (p < 0.001). The
      concentration of type II pneumocytes was similar between healthy controls and the
      FITO group, and was paradoxically increased in untreated hernia fetuses. There
      was no histological evidence of tracheal injury. CONCLUSION: FITO with a modified
      8-mm Z-stent is associated with lung growth and maturation similar to controls
      without obvious deleterious effects. A phase I clinical trial of FITO with the
      modified 8-mm Z-stent in severe CDH patients seems warranted.

PMID- 22631592
TI  - Prevention of cancer and non-communicable diseases.
AB  - Cancer is a leading cause of death worldwide, accounting for approximately 7.6
      million deaths (13% of all deaths) in 2008. Cancer mortality is projected to
      increase to 11 million deaths in 2030, with the majority occurring in regions of
      the world with the least capacity to respond. However, cancer is not only a
      personal, societal and economic burden but also a potential societal opportunity
      in the context of functional life - the years gained through effective prevention
      and treatment, and strategies to enhance survivorship. The United Nations General
      Assembly Special Session in 2011 has served to focus attention on key aspects of
      cancer prevention and control. Firstly, cancer is largely preventable, by
      feasible means. Secondly, cancer is one of a number of chronic, non- communicable
      diseases that share common risk factors whose prevention and control would
      benefit a majority of the world's population. Thirdly, a proportion of cancers
      can be attributed to infectious, communicable causal factors (e.g., HPV, HBV,
      H.pylori, parasites, flukes) and that strategies to control the burden of
      infectious diseases have relevance to the control of cancer. Fourthly, that the
      natural history of non-communicable diseases, including cancer, from primary
      prevention through diagnosis, treatment and care, is underwritten by the impact
      of social, economic and environmental determinants of health (e.g., poverty,
      illiteracy, gender inequality, social isolation, stigma, socio-economic status).
      Session 1 of the 4th International Cancer Control Congress (ICCC-4) focused on
      the social, economic and environmental, as well as biological and behavioural,
      modifiers of the risk of cancer through one plenary presentation and four
      interactive workshop discussions. The workshop sessions concerned 1) the Global
      Adult Tobacco Survey and social determinants of tobacco use in high burden low-
      and middle-income countries; 2) the role of diet, including alcohol, and physical
      activity in modifying the risk of cancer and other non-communicable diseases; 3)
      the role of infections in modifying the risk of cancer; and 4) the public
      policies and actions that can be implemented to effectively reduce the risk of
      cancer at population levels. Workshop discussions highlighted the need for high
      quality data on the prevalence of modifiable factors in different settings, as
      well as the social, economic and environmental drivers of these factors, in order
      to inform prevention and control programs. For some factors, further work needs
      to be done to develop simple and valid measurement tools. Given that many of
      these factors are common to both cancer and other non-communicable diseases,
      cancer prevention should be viewed within the broader perspective of the
      prevention of non-communicable diseases and should engage all relevant actors,
      including the general public, health and other professionals, workplaces and
      institutions, the media, civil society, schools, governments, industry, and
      multinational bodies. Many policies and plans have been implemented in various
      settings to control the drivers of modifiable factors and promote health and well
      being. Mapping, analysis, and contextualization of those policies that are
      relevant would be helpful to promote action around cancer prevention in different
      settings.

PMID- 22631593
TI  - Managing population health to prevent and detect cancer and non-communicable
      diseases.
AB  - The goals of cancer control strategies are generally uniform across all
      constituencies and are to reduce cancer incidence, reduce cancer mortality, and
      improve quality of life for those affected by cancer. A well-constructed strategy
      will ensure that all of its elements can ultimately be connected to one of these
      goals. When a cancer control strategy is being implemented, it is essential to
      map progress towards these goals; without mapping progress, it is impossible to
      assess which components of the strategy require more attention or resources and
      which are not having the desired effect and need to be re-evaluated. In order to
      monitor and evaluate these strategies, systems need to be put in place to collect
      data and the appropriate indicators of performance need to be identified. Session
      2 of the 4th International Cancer Control Congress (ICCC-4) focused on how to
      manage population health to prevent and detect cancers and non-communicable
      diseases through two plenary presentations and four interactive workshop
      discussions: 1) registries, measurement, and management in cancer control; 2) use
      of information for planning and evaluating screening and early detection
      programs; 3) alternative models for promoting community health, integrated care
      and illness management; and 4) control of non-communicable diseases. Workshop
      discussions highlighted that population based cancer registries are fundamental
      to understanding the cancer burden within a country. However, many countries in
      Africa, Asia, and South/ Central America do not have them in place. A new global
      initiative is underway, which brings together several international agencies, and
      aims to establish six IARC regional registration resource centres over the next
      five years. These will provide training, support, infrastructure and advocacy to
      local networks of cancer registries, and, it is hoped, improve the host
      countries' ability to assess and act on cancer issues within their jurisdictions.
      Multiple methods of programme evaluation were presented across workshops, but all
      were attuned to both the resource base and the specific questions to be
      addressed. Where innovative strategies were being tested, customized evaluation
      strategies should be undertaken. Where programmes are well-developed and data is
      being collected for evaluation, there is the opportunity for sophisticated
      analytical methods to be used to pinpoint specific areas or delivery sites for
      future quality improvement. Finally, unique opportunities now exist to integrate
      the strategies developed in cancer control and evaluation with those under
      development for other non-communicable diseases. This area will likely be one for
      future development.

PMID- 22631594
TI  - Coordinating care and treatment for cancer patients.
AB  - Survival following a diagnosis of cancer is contingent upon an interplay of
      factors, some non-modifiable (e.g., age, sex, genetics) and some modifiable
      (e.g., volitional choices) but the majority determined by circumstance (personal,
      social, health system context and capacity, and health policy). Accordingly,
      mortality and survival rates vary considerably as a function of geography,
      opportunity, wealth and development. Quality of life is impacted similarly, such
      that aspects of care related to coordination and integration of care across
      primary, community and specialist environments; symptom control, palliative and
      end-of-life care for those who will die of cancer; and survivorship challenges
      for those who will survive cancer, differs greatly across low, middle and high
      income resource settings. Session 3 of the 4th International Cancer Control
      Congress (ICCC-4) focused on cancer care and treatment through three plenary
      presentations and five interactive workshop discussions: 1) establishing,
      implementing, operating and sustaining the capacity for quality cancer care; 2)
      the role of primary, community, and specialist care in cancer care and treatment;
      3) the economics of affordable and sustainable cancer care; 4) issues around
      symptom control, support, and palliative/end-of-life care; and 5) issues around
      survivorship. A number of recommendations were proposed relating to capacity
      building (standards and guidelines, protocols, new technologies and training and
      deployment) for safe, appropriate evidence-informed care; mapping and analysis of
      variations in primary, community and specialist care across countries with
      identification of models for effective, integrated clinical practice; the
      importance of considering the introduction, or expansion, of evidence-supported
      clinical practices from the perspectives of health economic impact, the value for
      health resources expended, and sustainability; capacity-building for palliative,
      end-of-life care and symptom control and integration of these services into
      national cancer control plans; the need for public education to reduce the fear
      and stigma associated with cancer so that patients are better able to make
      informed decisions regarding follow-up care and treatment; and the need to
      recognize the challenges and needs of survivors, their increasing number, the
      necessity to integrate survivorship into cancer control plans and the economic
      and societal value of functional survival after cancer. Discussions highlighted
      that coordinated care and treatment for cancer patients is both a '
      systems'challenge and solution, requiring the consideration of patient and family
      circumstances, societal values and priorities, the functioning of the health
      system (access, capacity, resources, etc.) and the importance assigned to health
      and illness management within public policy.

PMID- 22631595
TI  - Knowledge exchange--translating research into practice and policy.
AB  - Substantial differences in population-based cancer control outcomes exist within
      and between nations. Optimal outcomes derive from 'what we know', 'what we apply
      in practice', and 'how complete and compliant is the population uptake of public
      health and clinical practice change'. This continuum of research (scientific
      discovery) to practice (application and uptake) to policy impacts the speed and
      completeness of practice change and is greatly influenced by the ability,
      opportunity and readiness of countries to implement evidence informed practices
      and policies through innovative change. Session 4 of the 4th International Cancer
      Control Congress focused on knowledge exchange through three plenary
      presentations and five interactive workshop discussions: 1) the role of
      epidemiological data as a basis for policy formulation; 2) existing global
      frameworks for cancer control; 3) knowledge exchange as it relates to public
      health practice and policy; 4) knowledge exchange in relation to primary,
      community, and specialist cancer care; and 5) the role of public engagement and
      advocacy in influencing cancer control policy. Common themes emerging from
      workshop discussions included the recognition of the importance of knowledge
      exchange processes, constituents and forums as key aspects of preparedness,
      awareness and readiness to implement public health and clinical practice change.
      The importance of cultural and contextual differences between nations was
      identified as a challenge requiring development of tools for generating relevant
      population/societal data (e.g., projection methodologies applied to population
      demographics, outcomes and resources, both societal, human and fiscal) and
      capacity building for facilitating knowledge transfer and exchange between the
      constituencies engaged in population-based public health practice and clinically
      based primary care and disease specialty practice exchange (researchers, health
      practitioners, health administrators, politicians, patients and families, and the
      private and public sectors). Understanding patient and public engagement advocacy
      and its role in influencing health and public policy investment priorities
      emerged as a critical and fundamental aspect of successful implementation of
      evidence-informed cancer control change.

PMID- 22631596
TI  - The 4th International Cancer Control Congress.

PMID- 22631597
TI  - Evaluation of humoral immune response to donor HLA after implantation of
      cellularized versus decellularized human heart valve allografts.
AB  - We have evaluated the development of antibodies in response to donor allograft
      valve implant in patients who received cellularized and decellularized allografts
      and determined possible immunogenic epitopes considered responsible for
      antibodies reactivity. Serum samples from all recipients who received
      cellularized allografts or decellularized allografts were collected before valve
      replacement and at 5, 10, 30 and 90 days post-operatively and frozen until
      required. Tests were performed using the Luminex-based single human leukocyte
      antigen (HLA)-A, -B, -C and HLA-DR, -DQ antigen microsphere assay. To determine
      possible immunogenic epitopes, we used the HLAMatchmaker (HLAMM) software if
      applicable. Decellularized grafts elicited lower levels of anti-HLA class I and
      II antibody formation after implantation than cellularized allografts. All
      patients from cellularized group presented donor-specific antibodies class I and
      II within 3 months of observation period. In HLAMM analysis, the cellularized
      group had significantly higher numbers of immunogenic epitopes than
      decellularized group for both class I and II (p: 0.002 - cl I / p: 0.009 - cl II
      / p: 0.004 - cl I and II). Our findings demonstrate that the anti-HLA antibodies
      detected in the cellularized group were against donor HLA possible immunogenic
      epitopes and that in the decellularized group the anti-HLA antibodies were not
      against donor HLA possible immunogenic epitopes. These findings lead us to
      suggest that choosing sodium dodecyl sulfate decellularization process is the
      best alternative to decrease the immunogenicity of allograft valve transplant.

PMID- 22631598
TI  - Poststroke infections are an independent risk factor for poor functional outcome
      after three-months in thrombolysed stroke patients.
AB  - BACKGROUND: Infections are common complications in patients with acute ischemic
      stroke; however, the pathophysiology of the stroke-induced immunodepression is
      still under debate. Although it has been shown that increased mortality and
      longer hospital stay are associated with the presence of poststroke infections,
      it remains unclear if early poststroke infections occurring in the first seven
      days have an effect on the overall functional outcome. AIMS: Aim of our study was
      to identify the frequency of poststroke infections in thrombolysed stroke
      patients and to analyze their effect on the outcome after three-months. METHODS:
      From 1998 to 2011, all patients in our institution undergoing thrombolysis for
      acute ischemic stroke were included into a prospective database. Baseline
      variables, clinical, radiographic, and laboratory data were collected
      prospectively. Outcome measures included symptomatic intracerebral hemorrhage per
      European-Australasian Acute Stroke Study II criteria, mortality, and modified
      Rankin Scale at three-months. Logistic regression models were used to identify
      independent predictors for poor outcome where appropriate. RESULTS: One thousand
      sixteen patients were included; of them, 36.3% had an infection during the first
      week. Pneumonia (9.6%) and urinary tract infections (5.4%) were most frequent.
      Severity of stroke (P < 0.0001), infarct size (P < 0.0001), atrial fibrillation
      (P = 0.005), and cardio embolic cause of stroke (P < 0.0001) were associated with
      infections. Age (odds ratio 1.089, 95% confidence interval 1.064-1.115, P <
      0.0001), severity of stroke (odds ratio 1.111, 95% confidence interval 1.073
      1.149; P < 0.0001) history of diabetes (odds ratio 0.555. 95% confidence interval
      0.357-0.864; P = 0.009), infarct size (odds ratio 4.256 95% confidence interval
      2.697-6.745; P < 0.0001), infections (odds ratio 1.548, 95% confidence interval
      1.008-2.376; P = 0.046), and symptomatic intracerebral hemorrhage were
      independent predictors for poor outcome after three-months. CONCLUSIONS: In our
      cohort of thrombolysed stroke patients, poststroke infections were frequent in
      patients with severe cardio embolic stroke, a large infarct, and a longer
      hospital stay; those patients have a higher risk of infection and a poorer
      functional outcome after three-months. This risk increases after occurrence of
      symptomatic intracerebral hemorrhage. Prevention of infection with antibiotic
      therapy or other prophylactic treatment could potentially lead to a better
      functional outcome and further randomized studies on this aspect are needed.

PMID- 22631599
TI  - Spinal mechanisms of pain and analgesia.
AB  - Chronic pain--especially that which is refractory to conventional treatment-
      presents particular challenges to physicians and patients. Examination of the
      molecular and cellular mechanisms involved in this pathophysiology suggests that
      spinal instillation of therapeutic agents may offer an effective treatment option
      through the modification of the processing and sensation of chronic pain.
      Intrathecal therapy, used alone or in combination with other analgesic agents,
      may reduce chronic pain by attenuating both pre- and postsynaptic activities.
      This article reviews chronic pain pathophysiology and the mechanisms whereby
      spinally administered analgesics may modify chronic pain. Available treatment
      options are also considered, including recommendations from the 2007
      Polyanalgesic Consensus Conference (PACC) guidelines on the use of intrathecal
      agents for nociceptive, neuropathic, and mixed pain.

PMID- 22631600
TI  - Rapid injection NMR reveals eta3 'pi-allyl' Cu(III) intermediates in addition
      reactions of organocuprate reagents.
AB  - By using rapid injection NMR, it has now been possible to prepare and
      characterize the eta(3) 'pi-allyl' copper(III) intermediate that has been
      proposed for addition reactions of organocopper(I) reagents and alpha,beta
      unsaturated carbonyl compounds.

PMID- 22631601
TI  - A systems biology analysis of long and short-term memories of osmotic stress
      adaptation in fungi.
AB  - BACKGROUND: Saccharomyces cerevisiae senses hyperosmotic conditions via the HOG
      signaling network that activates the stress-activated protein kinase, Hog1, and
      modulates metabolic fluxes and gene expression to generate appropriate adaptive
      responses. The integral control mechanism by which Hog1 modulates glycerol
      production remains uncharacterized. An additional Hog1-independent mechanism
      retains intracellular glycerol for adaptation. Candida albicans also adapts to
      hyperosmolarity via a HOG signaling network. However, it remains unknown whether
      Hog1 exerts integral or proportional control over glycerol production in C.
      albicans. RESULTS: We combined modeling and experimental approaches to study
      osmotic stress responses in S. cerevisiae and C. albicans. We propose a simple
      ordinary differential equation (ODE) model that highlights the integral control
      that Hog1 exerts over glycerol biosynthesis in these species. If integral control
      arises from a separation of time scales (i.e. rapid HOG activation of glycerol
      production capacity which decays slowly under hyperosmotic conditions), then the
      model predicts that glycerol production rates elevate upon adaptation to a first
      stress and this makes the cell adapts faster to a second hyperosmotic stress. It
      appears as if the cell is able to remember the stress history that is longer than
      the timescale of signal transduction. This is termed the long-term stress memory.
      Our experimental data verify this. Like S. cerevisiae, C. albicans mimimizes
      glycerol efflux during adaptation to hyperosmolarity. Also, transient activation
      of intermediate kinases in the HOG pathway results in a short-term memory in the
      signaling pathway. This determines the amplitude of Hog1 phosphorylation under a
      periodic sequence of stress and non-stressed intervals. Our model suggests that
      the long-term memory also affects the way a cell responds to periodic stress
      conditions. Hence, during osmohomeostasis, short-term memory is dependent upon
      long-term memory. This is relevant in the context of fungal responses to dynamic
      and changing environments. CONCLUSIONS: Our experiments and modeling have
      provided an example of identifying integral control that arises from time-scale
      separation in different processes, which is an important functional module in
      various contexts.

PMID- 22631603
TI  - Association of neonicotinoid insensitivity with a conserved residue in the loop d
      binding region of the tick nicotinic acetylcholine receptor.
AB  - Neonicotinoid insecticides target nicotinic acetylcholine receptors (nAChR) in
      the nervous system of insects but are largely ineffective against ticks. This
      study aimed to identify the molecular basis for this insensitivity. A homology
      model of the nAChR binding domain was generated on the basis of the crystal
      structure of an acetylcholine-binding protein with the insecticide imidacloprid
      bound. We hypothesized that tick beta-subunits would differ at a critical residue
      (Arg81) in their D loops. To test this, we sequenced nAChR genes from five tick
      species and found that instead of the conserved arginine found in insects, a
      glutamine was present in all the tick sequences.

PMID- 22631602
TI  - Study of charge transport mechanisms in (125)I-induced DNA damage at various
      temperatures.
AB  - PURPOSE: Iodine-125 decay induces localized DNA damage by three major mechanisms:
      (1) Direct damage by the emitted Auger electrons, (2) indirect damage by
      diffusible free radicals, and (3) charge neutralization of the residual, highly
      positively charged, tellurium daughter atom by stripping electrons from
      neighboring residues. The charge neutralization mechanism of (125)I-induced DNA
      damage is poorly understood. Charge transport along a DNA molecules can occur by
      either a hopping mechanism initiated by charge injection into DNA and propagated
      by charge migration through DNA bases along the DNA length, or by a tunneling
      mechanism in which charge transfers directly from a donor to an acceptor residue.
      In the first case additional damage in DNA nucleotides can be inflicted by the
      traveling charge; therefore, it is important to learn if charge hopping plays a
      role in (125)I-decay-induced DNA damage. In our previous work, we determined that
      at 193K the charge hopping mechanism was not an appreciable component of the
      mechanism of (125)I-induced DNA damage. However, the question whether this is
      also the case at higher temperatures remained open. METHODS: In the current study
      we used a well-known chemical barrier for charge hopping, 8-oxo-7, 8,
      dihydroguanine (8-oxo-G), to assess the role of this mechanism in (125)I-decay
      induced DNA damage at the following temperatures: 198, 253, 277 and 298 K.
      RESULTS: We found that varying the temperature had little effect on the
      distribution of (125)I-induced DNA breaks, as well as on the breaks found at the
      8-oxo-G probe both with and without piperidine treatment. CONCLUSIONS: We thus
      conclude that charge transport by the hopping mechanism is not a major factor in
      (125)I-decay-induced DNA damage at biologically relevant temperatures.

PMID- 22631604
TI  - Efficient transfer of large-area graphene films onto rigid substrates by hot
      pressing.
AB  - Graphene films grown on metal substrates by chemical vapor deposition (CVD)
      method have to be safely transferred onto desired substrates for further
      applications. Recently, a roll-to-roll (R2R) method has been developed for large
      area transfer, which is particularly efficient for flexible target substrates.
      However, in the case of rigid substrates such as glass or wafers, the roll-based
      method is found to induce considerable mechanical damages on graphene films
      during the transfer process, resulting in the degradation of electrical property.
      Here we introduce an improved dry transfer technique based on a hot-pressing
      method that can minimize damage on graphene by neutralizing mechanical stress.
      Thus, we enhanced the transfer efficiency of the large-area graphene films on a
      substrate with arbitrary thickness and rigidity, evidenced by scanning electron
      microscope (SEM) and atomic force microscope (AFM) images, Raman spectra, and
      various electrical characterizations. We also performed a theoretical multiscale
      simulation from continuum to atomic level to compare the mechanical stresses
      caused by the R2R and the hot-pressing methods, which also supports our
      conclusion. Consequently, we believe that the proposed hot-pressing method will
      be immediately useful for display and solar cell applications that currently
      require rigid and large substrates.

PMID- 22631605
TI  - Diffuse symmetric meningioma en plaque mimicking metabolic disease of bone.
AB  - A 50-year-old African American woman with right proptosis and decreased vision
      demonstrated symmetric, bilateral thickening of the sphenoid wings, calvarium,
      and skull base on computed tomography. Histopathologic evaluation of the
      hyperostotic lesion was consistent with meningotheliomatous meningioma. The
      patient underwent uncomplicated right frontal orbital craniectomy with
      postoperative radiation. The presentation of en plaque meningioma, when diffuse
      and symmetric, can mimic a metabolic disease of bone.

PMID- 22631606
TI  - A mini-symposium of 2nd Japanese Society for Investigative Dermatology-Asia
      Oceania-Forum.

PMID- 22631608
TI  - Psychometric features of temporomandibular disorders patients in relation to pain
      diffusion, location, intensity and duration.
AB  - The aim of the present investigation was to assess the psychological profile of a
      sample of patients with temporomandibular disorders (TMD) and to compare the
      psychometric scores between patients with pain of different diffusion, location,
      intensity and duration. One hundred and ten (N = 110) patients with painful TMD
      fulfilled three psychometric instruments. Pain features were assessed as
      categorical variables as concerns its diffusion, viz., diffuse or localised,
      duration, viz., more or <6 months, and location, viz., joint and/or muscles. Pain
      intensity was scored on a 0-100 Visual Analog Scale (VAS) rating. Patients with
      diffuse pain showed higher psychometric scores than patients with localised pain.
      No significant differences were detected between patients with pain lasting from
      more or equal than 6 months and those with pain lasting from <6 months as well as
      between patients with pain localised in the jaw muscles, joints or both, even if
      a trend for lower scores for patients with joint pain alone was observed. Pain
      intensity was significantly related with anxiety (ANX), depression (DEP) and
      somatisation(SOM) scores. In conclusion, pain diffusion and intensity were
      strongly related with high levels of SOM, ANX and DEP, while no differences in
      psychometric scores were detected between patients with pain of different
      duration and location.

PMID- 22631609
TI  - Assessment of patient satisfaction following external versus transcanalicular
      dacryocystorhinostomy.

PMID- 22631607
TI  - Monitoring lipid anchor organization in cell membranes by PIE-FCCS.
AB  - This study examines the dynamic co-localization of lipid-anchored fluorescent
      proteins in living cells using pulsed-interleaved excitation fluorescence cross
      correlation spectroscopy (PIE-FCCS) and fluorescence lifetime analysis.
      Specifically, we look at the pairwise co-localization of anchors from lymphocyte
      cell kinase (LCK: myristoyl, palmitoyl, palmitoyl), RhoA (geranylgeranyl), and K
      Ras (farnesyl) proteins in different cell types. In Jurkat cells, a density
      dependent increase in cross-correlation among RhoA anchors is observed, while LCK
      anchors exhibit a more moderate increase and broader distribution. No correlation
      was detected among K-Ras anchors or between any of the different anchor types
      studied. Fluorescence lifetime data reveal no significant Forster resonance
      energy transfer in any of the data. In COS 7 cells, minimal correlation was
      detected among LCK or RhoA anchors. Taken together, these observations suggest
      that some lipid anchors take part in anchor-specific co-clustering with other
      existing clusters of native proteins and lipids in the membrane. Importantly,
      these observations do not support a simple interpretation of lipid anchor
      mediated organization driven by partitioning based on binary lipid phase
      separation.

PMID- 22631610
TI  - Epidemiological and clinical description of the top three reportable parasitic
      diseases in a Canadian community.
AB  - This study provides a comprehensive epidemio-clinical picture of sporadic,
      domestically acquired cases of amoebiasis, cryptosporidiosis and giardiasis in
      one Canadian community based on patient symptom, outcome and exposure data from
      an enhanced surveillance system. It yields valuable data for estimating the
      burden of those diseases including the proportion of bloody diarrhoea,
      hospitalization, and disease duration. Age differences were observed by incidence
      rate and for some clinical information and exposures to risk factors. For each of
      the three diseases, the animal/environment-to-person route was the most common
      possible main transmission route according to the exposure reported, whereas the
      person-to-person route was the least common. Exposure was higher for the 10-24
      years age group of giardiasis cases for swimming in recreational waters (79%) and
      attending a barbeque (50%). Therefore, comparisons between groups of cases or
      extrapolation of results when estimating the burden of illness should be adjusted
      for age.

PMID- 22631611
TI  - Combined portal vein embolization and preoperative chemotherapy prior to liver
      resection for colorectal cancer metastases.
AB  - OBJECTIVE: Compare perioperative course and long-term mortality after liver
      resection for colorectal cancer (CRC) metastases between patients who had
      preoperative treatment with portal vein embolization (PVE) and chemotherapy or
      chemotherapy alone. METHODS: Among patients undergoing liver resection for CRC
      metastases following preoperative chemotherapy treatment, 17 patients who had
      received preoperative PVE (group A) were compared with 17 matched controls who
      had no PVE (group B). Perioperative course and long-term mortality were compared
      between groups A and B and between group A and the entire group of 75 cases with
      preoperative chemotherapy (group C). RESULTS: Baseline characteristics for the
      matched groups A and B were similar. Group C included less major resections.
      Median intraoperative bleeding was 1600 ml in group A, 1200 ml in group B, and
      1000 ml in group C (p < 0.05 vs. group A). Median postoperative stay was
      comparable in all groups (8-9 days). Operation time was 542 min in group A and
      464 min in group B (p < 0.01). Mortality after 30 days and 1, 2, and 5 years was
      similar in all groups. CONCLUSION: Perioperative outcome and long-term survival
      did not differ when comparing liver resection for CRC liver metastases preceded
      by PVE and chemotherapy or chemotherapy alone, except for the operation time. The
      study supports the safety of this "aggressive" combination approach in patients
      in need of tumor "downstaging" by chemotherapy and PVE to increase the remnant
      liver volume.

PMID- 22631612
TI  - Amyloid beta 1-42 inhibits entorhinal cortex activity in the beta-gamma range:
      role of GSK-3.
AB  - Oscillatory activity in the entorhinal cortex has been associated with several
      cognitive functions. Accordingly, Alzheimer Disease-associated cognitive decline
      has been related to amyloid beta-induced disturbances in several of these
      oscillatory patterns. We have previously shown that acute application of amyloid
      beta inhibits the generation of slow frequency oscillations (7-20 Hz). In
      contrast, alterations in faster oscillations recorded in Alzheimer Disease
      transgenic mice that over-express amyloid beta have been controversial. Since
      transgenic mice may produce complex responses due to compensatory mechanisms, we
      tested the effect of acute application of amyloid beta on fast oscillations (beta
      gamma bursts) generated by entorhinal cortex slices in vitro in a Mg2+ -ree
      solution. We also explored the participation of the enzyme glycogen synthase
      kinase 3 (GSK-3) in this effect. Our results show that bath application of a
      clinically relevant concentration of amyloid beta (10 nM) activates GSK-3 and
      reduces the power of beta-gamma bursts in the entorhinal cortex. The reduction of
      beta-gamma bursts by amyloid beta is blocked by inhibiting GSK-3 either with
      lithium or with SB 216763. Our results suggest that amyloid beta-induced
      inhibition of entorhinal cortex beta-gamma activity involves GSK-3 activation,
      which may provide a molecular mechanism for amyloid beta-induced neural network
      disruption and support the use of GSK-3 inhibitors to treat Alzheimer Disease.

PMID- 22631613
TI  - Chronic administration of an aglycosylated murine antibody of ponezumab does not
      worsen microhemorrhages in aged Tg2576 mice.
AB  - Cerebral vasogenic edema and microhemorrhages are potential safety concerns for
      compounds intended to treat subjects with Alzheimer's disease (AD) by targeting
      amyloid beta (Abeta). Ponezumab (PF-04360365) is an investigational anti-Abeta
      monoclonal antibody. Two hundred female mice (APP(K670N;M671L); Tg2576) 16-19
      months old received an aglycosylated CHO-derived murine surrogate of ponezumab by
      intraperitoneal administration once weekly for up to 26 weeks at doses of 0, 10,
      30, or 100 mg/kg. Drug exposure and plasma Abeta levels increased with increasing
      dose. After 26 weeks, the 100 mg/kg group had significantly greater plasma levels
      of Abeta(1-x) and Abeta(x-40) than the vehicle group (p < 0.001). Brain
      microhemorrhages were identified histologically using hematoxylin and eosin
      and/or Perls' Prussian blue iron staining. The incidence in the vehicle group was
      equal to or higher than those of the treated groups. There was no evidence of
      vasogenic edema. In summary, intraperitoneal administration of a murine surrogate
      of ponezumab to aged Tg2576 mice for up to 6 months did not produce any compound
      related brain microhemorrhage or other pathologies.

PMID- 22631614
TI  - Mechanisms involved in BACE upregulation associated to stress.
AB  - The objective of the present work was to study a purported involvement of stress
      in amyloid pathology through the modulation of BACE expression. Early-life
      stressed rats (maternal separation, MS) showed significant increases in
      corticosterone levels, BACE expression and Abeta levels. The CpG7 site of the
      BACE promoter was significantly hypomethylated in MS, and corticosterone levels
      negatively correlated to the methylation status of CpG7. The activation of the
      stress-activated protein kinase JNK was also increased in MS rats. In SHSY-5Y
      neuroblastoma cells, corticosterone induced a rapid increase in BACE expression
      that was abolished by specific inhibiton of JNK activation or by spironolactone,
      a mineralocorticoid receptor antagonist, but not by mifepristone, a
      glucocorticoid receptor antagonist. Corticosterone was also able to increase pJNK
      expression and this effect was fully reverted by spironolactone. Mice chronically
      treated with corticosterone showed increased BACE and pJNK expression. These
      increases were reverted by treatment with spironolactone or with a JNK inhibitor.
      It is suggested that increased corticosterone levels associated to stress lead to
      increase BACE transcription both through epigenetic mechanisms and activation of
      JNK.

PMID- 22631615
TI  - Nickel allergy in relation to piercing and orthodontic appliances--a population
      study.
AB  - BACKGROUND: Studies have shown conflicting results on the association between
      nickel exposure from orthodontic appliances and nickel sensitization. OBJECTIVES
      & METHOD: In a cross-sectional study, we investigated the association between
      nickel sensitization and exposure to orthodontic appliances and piercings. 4376
      adolescents were patch tested following a questionnaire asking for earlier
      piercing and orthodontic treatment. Exposure to orthodontic appliances was
      verified in dental records. RESULTS: Questionnaire data demonstrated a reduced
      risk of nickel sensitization when orthodontic treatment preceded piercing (OR
      0.46; CI 0.27-0.78). Data from dental records demonstrated similar results (OR
      0.61, CI 0.36-1.02), but statistical significance was lost when adjusting for
      background factors. Exposure to full, fixed appliances with NiTi-containing
      alloys (OR 0.31, CI 0.10-0.98) as well as a pooled 'high nickel-releasing'
      appliance group (OR 0.56, CI 0.32-0.97) prior to piercing was associated with a
      significantly reduced risk of nickel sensitization. CONCLUSION: High nickel
      containing orthodontic appliances preceding piercing reduces the risk of nickel
      sensitization by a factor 1.5-2. The risk reduction is associated with estimated
      nickel release of the appliance and length of treatment. Sex, age at piercing and
      number of piercings are also important risk indicators. Research on the role of
      dental materials in the development of immunological tolerance is needed.

PMID- 22631616
TI  - Comparative effectiveness of cognitive behavioral therapy for insomnia: a
      systematic review.
AB  - BACKGROUND: Insomnia is common in primary care, can persist after co-morbid
      conditions are treated, and may require long-term medication treatment. A
      potential alternative to medications is cognitive behavioral therapy for insomnia
      (CBT-I). METHODS: In accordance with PRISMA guidelines, we systematically
      reviewed MEDLINE, EMBASE, the Cochrane Central Register, and PsycINFO for
      randomized controlled trials (RCTs) comparing CBT-I to any prescription or non
      prescription medication in patients with primary or comorbid insomnia. Trials had
      to report quantitative sleep outcomes (e.g. sleep latency) in order to be
      included in the analysis. Extracted results included quantitative sleep outcomes,
      as well as psychological outcomes and adverse effects when available. Evidence
      base quality was assessed using GRADE. RESULTS: Five studies met criteria for
      analysis. Low to moderate grade evidence suggests CBT-I has superior
      effectiveness to benzodiazepine and non-benzodiazepine drugs in the long term,
      while very low grade evidence suggests benzodiazepines are more effective in the
      short term. Very low grade evidence supports use of CBT-I to improve
      psychological outcomes. CONCLUSIONS: CBT-I is effective for treating insomnia
      when compared with medications, and its effects may be more durable than
      medications. Primary care providers should consider CBT-I as a first-line
      treatment option for insomnia.

PMID- 22631618
TI  - Emotion processing and regulation in bipolar disorder: a review.
AB  - OBJECTIVES: Bipolar disorder (BP) is characterized by a dysfunction of mood,
      alternating between states of mania/hypomania and depression. Thus, the primary
      abnormality appears to be an inability to regulate emotion, the result of which
      is emotional extremes. The purpose of this paper is to review the current
      functional magnetic resonance imaging (fMRI) literature on adult patients with BP
      using emotion processing or regulation paradigms. METHODS: A search was conducted
      on PubMed using the keywords: bipolar disorder, fMRI, mania, bipolar depression,
      bipolar euthymia, emotion, and amygdala. Only those studies that were conducted
      in adult patients using an emotion activation task were included in the final
      review. RESULTS: Using tasks that assess neural functioning during emotion
      processing and emotion regulation, many fMRI studies have examined BP subjects
      during mania and euthymia. Fewer fMRI studies have been conducted during
      depression, and fewer still have included the same subjects in multiple mood
      states. Despite these limitations, these studies have demonstrated specific
      abnormalities in frontal-limbic regions. Using a variety of paradigms,
      investigators have specifically evaluated the amygdala (a structure within the
      limbic system known to be critical for emotion) and the prefrontal cortex (PFC)
      (a region known to have a regulatory function over the limbic system).
      CONCLUSIONS: These investigations reveal that amygdala activation varies as a
      function of mood state, while the PFC remains persistently hypoactivated across
      mood states. Emotional dysregulation and lability in mania and depression may
      reflect disruption of a frontal-limbic functional neuroanatomical network.

PMID- 22631617
TI  - The functional neuroanatomy of bipolar disorder: a consensus model.
AB  - OBJECTIVES: Functional neuroimaging methods have proliferated in recent years,
      such that functional magnetic resonance imaging, in particular, is now widely
      used to study bipolar disorder. However, discrepant findings are common. A
      workgroup was organized by the Department of Psychiatry, University of Cincinnati
      (Cincinnati, OH, USA) to develop a consensus functional neuroanatomic model of
      bipolar I disorder based upon the participants' work as well as that of others.
      METHODS: Representatives from several leading bipolar disorder neuroimaging
      groups were organized to present an overview of their areas of expertise as well
      as focused reviews of existing data. The workgroup then developed a consensus
      model of the functional neuroanatomy of bipolar disorder based upon these data.
      RESULTS: Among the participants, a general consensus emerged that bipolar I
      disorder arises from abnormalities in the structure and function of key emotional
      control networks in the human brain. Namely, disruption in early development
      (e.g., white matter connectivity and prefrontal pruning) within brain networks
      that modulate emotional behavior leads to decreased connectivity among ventral
      prefrontal networks and limbic brain regions, especially the amygdala. This
      developmental failure to establish healthy ventral prefrontal-limbic modulation
      underlies the onset of mania and ultimately, with progressive changes throughout
      these networks over time and with affective episodes, a bipolar course of
      illness. CONCLUSIONS: This model provides a potential substrate to guide future
      investigations and areas needing additional focus are identified.

PMID- 22631620
TI  - Neuroprogression in bipolar disorder.
AB  - OBJECTIVE: Recent theories regarding the neuropathology of bipolar disorder
      suggest that both neurodevelopmental and neurodegenerative processes may play a
      role. While magnetic resonance imaging has provided significant insight into the
      structural, functional, and connectivity abnormalities associated with bipolar
      disorder, research assessing longitudinal changes has been more limited. However,
      such research is essential to elucidate the pathophysiology of the disorder. The
      aim of our review is to examine the extant literature for developmental and
      progressive structural and functional changes in individuals with and at risk for
      bipolar disorder. METHODS: We conducted a literature review using MEDLINE and the
      following search terms: bipolar disorder, risk, child, adolescent, bipolar
      offspring, MRI, fMRI, DTI, PET, SPECT, cross-sectional, longitudinal,
      progressive, and developmental. Further relevant articles were identified by
      cross-referencing with identified manuscripts. CONCLUSIONS: There is some
      evidence for developmental and progressive neurophysiological alterations in
      bipolar disorder, but the interpretation of correlations between neuroimaging
      findings and measures of illness exposure or age in cross-sectional studies must
      be performed with care. Prospective longitudinal studies placed in the context of
      normative developmental and atrophic changes in neural structures and pathways
      thought to be involved in bipolar disorder are needed to improve our
      understanding of the neurodevelopmental underpinnings and progressive changes
      associated with bipolar disorder.

PMID- 22631621
TI  - Effects of medication on neuroimaging findings in bipolar disorder: an updated
      review.
AB  - OBJECTIVE: Neuroimaging is an important tool for better understanding the
      neurobiological underpinnings of bipolar disorder (BD). However, potential study
      participants are often receiving psychotropic medications which can possibly
      confound imaging data. To better interpret the results of neuroimaging studies in
      BD, it is important to understand the impact of medications on structural
      magnetic resonance imaging (sMRI), functional MRI (fMRI), and diffusion tensor
      imaging (DTI). METHODS: To better understand the impact of medications on imaging
      data, we conducted a literature review and searched MEDLINE for papers that
      included the key words bipolar disorder and fMRI, sMRI, or DTI. The search was
      limited to papers that assessed medication effects and had not been included in a
      previous review by Phillips et al. (Medication effects in neuroimaging studies of
      bipolar disorder. Am J Psychiatry 2008; 165: 313-320). This search yielded 74
      sMRI studies, 46 fMRI studies, and 15 DTI studies. RESULTS: Medication appeared
      to influence many sMRI studies, but had limited impact on fMRI and DTI findings.
      From the structural studies, the most robust finding (20/45 studies) was that
      lithium was associated with increased volumes in areas important for mood
      regulation, while antipsychotic agents and anticonvulsants were generally not.
      Regarding secondary analysis of the medication effects of fMRI and DTI studies,
      few showed significant effects of medication, although rigorous analyses were
      typically not possible when the majority of subjects were medicated. Medication
      effects were more frequently observed in longitudinal studies designed to assess
      the impact of particular medications on the blood oxygen level-dependent (BOLD)
      signal. With a few exceptions, the observed effects were normalizing, meaning
      that the medicated individuals with BD were more similar than their unmedicated
      counterparts to healthy subjects. CONCLUSIONS: The effects of psychotropic
      medications, when present, are predominantly normalizing and thus do not seem to
      provide an alternative explanation for differences in volume, white matter
      tracts, or BOLD signal between BD participants and healthy subjects. However, the
      normalizing effects of medication could obfuscate differences between BD and
      healthy subjects, and thus might lead to type II errors.

PMID- 22631622
TI  - Review of functional magnetic resonance imaging studies comparing bipolar
      disorder and schizophrenia.
AB  - OBJECTIVE: Although bipolar disorder (BD) and schizophrenia (SCZ) have a number
      of clinical features and certain susceptibility genes in common, they are
      considered separate disorders, and it is unclear which aspects of pathophysiology
      are specific to each condition. Here, we examine the functional magnetic
      resonance imaging (fMRI) literature to determine the evidence for diagnosis
      specific patterns of brain activation in the two patient groups. METHOD: A
      systematic search was performed to identify fMRI studies directly comparing BD
      and SCZ to examine evidence for diagnosis-specific activation patterns. Studies
      were categorized into (i) those investigating emotion, reward, or memory, (ii)
      those describing executive function or language tasks, and (iii) those looking at
      the resting state or default mode networks. Studies reporting estimates of
      sensitivity and specificity of classification are also summarized, followed by
      studies reporting associations with symptom severity measures. RESULTS: In total,
      21 studies were identified including patients (n = 729) and healthy subjects (n =
      465). Relative over-activation in the medial temporal lobe and associated
      structures was found in BD versus SCZ in tasks involving emotion or memory.
      Evidence of differences between the disorders in prefrontal regions was less
      consistent. Accuracy values for assignment of diagnosis were generally lower in
      BD than in SCZ. Few studies reported significant symptom associations; however,
      these generally implicated limbic regions in association with manic symptoms.
      CONCLUSIONS: Although there are a limited number of studies and a cautious
      approach is warranted, activation differences were found in the medial temporal
      lobe and associated limbic regions, suggesting the presence of differences in the
      neurobiological substrates of SCZ and BD. Future studies examining symptom
      dimensions, risk-associated genes, and the effects of medication will aid
      clarification of the mechanisms behind these differences.

PMID- 22631619
TI  - Functional neuroanatomy of bipolar disorder: structure, function, and
      connectivity in an amygdala-anterior paralimbic neural system.
AB  - OBJECTIVES: In past decades, neuroimaging research in bipolar disorder has
      demonstrated a convergence of findings in an amygdala-anterior paralimbic cortex
      neural system. This paper reviews behavioral neurology literature that first
      suggested a central role for this neural system in the disorder and the
      neuroimaging evidence that supports it. METHODS: Relevant articles are reviewed
      to provide an amygdala-anterior paralimbic cortex neural system model of bipolar
      disorder, including articles from the fields of behavioral neurology and
      neuroanatomy, and neuroimaging. RESULTS: The literature is highly supportive of
      key roles for the amygdala, anterior paralimbic cortices, and connections among
      these structures in the emotional dysregulation of bipolar disorder. The
      functions subserved by their more widely distributed connection sites suggest
      that broader system dysfunction could account for the range of functions-from
      neurovegetative to cognitive-disrupted in the disorder. Abnormalities in some
      components of this neural system are apparent by adolescence, while others, such
      as those in rostral prefrontal regions, appear to progress over adolescence and
      young adulthood, suggesting a neurodevelopmental model of the disorder. However,
      some findings conflict, which may reflect the small sample sizes of some studies,
      and clinical heterogeneity and methodological differences across studies.
      CONCLUSIONS: Consistent with models derived from early behavioral neurology
      studies, neuroimaging studies support a central role for an amygdala-anterior
      paralimbic neural system in bipolar disorder, and implicate abnormalities in the
      development of this system in the disorder. This system will be an important
      focus of future studies on the developmental pathophysiology, detection,
      treatment, and prevention of the disorder.

PMID- 22631623
TI  - Deficits in inferior frontal cortex activation in euthymic bipolar disorder
      patients during a response inhibition task.
AB  - OBJECTIVES: The inferior frontal cortical-striatal network plays an integral role
      in response inhibition in normal populations. While inferior frontal cortex (IFC)
      impairment has been reported in mania, this study explored whether this
      dysfunction persists in euthymia. METHODS: Functional magnetic resonance imaging
      (fMRI) activation was evaluated in 32 euthymic patients with bipolar I disorder
      and 30 healthy subjects while performing the Go/NoGo response inhibition task.
      Behavioral data were collected to evaluate accuracy and response time. Within
      group and between-group comparisons of activation were conducted using whole
      brain analyses to probe significant group differences in neural function.
      RESULTS: Both groups activated bilateral IFC. However, between-group comparisons
      showed a significantly reduced activation in this brain region in euthymic
      patients with bipolar disorder compared to healthy subjects. Other frontal and
      basal ganglia regions involved in response inhibition were additionally
      significantly reduced in bipolar disorder patients, in both the medicated and the
      unmedicated subgroups. No areas of greater activation were observed in bipolar
      disorder patients versus healthy subjects. CONCLUSIONS: Bipolar disorder
      patients, even during euthymia, have a persistent reduction in activation of
      brain regions involved in response inhibition, suggesting that reduced activation
      in the orbitofrontal cortex and striatum is not solely related to the state of
      mania. These findings may represent underlying trait abnormalities in bipolar
      disorder.

PMID- 22631624
TI  - Pattern recognition analyses of brain activation elicited by happy and neutral
      faces in unipolar and bipolar depression.
AB  - OBJECTIVES: Recently, pattern recognition approaches have been used to classify
      patterns of brain activity elicited by sensory or cognitive processes. In the
      clinical context, these approaches have been mainly applied to classify groups of
      individuals based on structural magnetic resonance imaging (MRI) data. Only a few
      studies have applied similar methods to functional MRI (fMRI) data. METHODS: We
      used a novel analytic framework to examine the extent to which unipolar and
      bipolar depressed individuals differed on discrimination between patterns of
      neural activity for happy and neutral faces. We used data from 18 currently
      depressed individuals with bipolar I disorder (BD) and 18 currently depressed
      individuals with recurrent unipolar depression (UD), matched on depression
      severity, age, and illness duration, and 18 age- and gender ratio-matched healthy
      comparison subjects (HC). fMRI data were analyzed using a general linear model
      and Gaussian process classifiers. RESULTS: The accuracy for discriminating
      between patterns of neural activity for happy versus neutral faces overall was
      lower in both patient groups relative to HC. The predictive probabilities for
      intense and mild happy faces were higher in HC than in BD, and for mild happy
      faces were higher in HC than UD (all p < 0.001). Interestingly, the predictive
      probability for intense happy faces was significantly higher in UD than BD (p =
      0.03). CONCLUSIONS: These results indicate that patterns of whole-brain neural
      activity to intense happy faces were significantly less distinct from those for
      neutral faces in BD than in either HC or UD. These findings indicate that pattern
      recognition approaches can be used to identify abnormal brain activity patterns
      in patient populations and have promising clinical utility as techniques that can
      help to discriminate between patients with different psychiatric illnesses.

PMID- 22631625
TI  - Sex differences in bipolar disorder: a review of neuroimaging findings and new
      evidence.
AB  - OBJECTIVES: The sex of an individual is known to modulate the clinical
      presentation of bipolar disorder (BD), but little is known as to whether there
      are significant sex-by-diagnosis interactions on the brain structural and
      functional correlates of BD. METHODS: We conducted a literature review of
      magnetic resonance imaging (MRI) studies in BD, published between January 1990
      and December 2010, reporting on the effects of sex and diagnosis. In the absence
      of any functional MRI (fMRI) studies, this review was supplemented by original
      data analyses focusing on sex-by-diagnosis interactions on patterns of brain
      activation obtained during tasks of working memory, incentive decision-making,
      and facial affect processing. RESULTS: We found no support for a sex-by-diagnosis
      interaction in global gray or white matter volume. Evidence regarding regional
      volumetric measures is limited, but points to complex interactions between sex
      and diagnosis with developmental and temperamental factors within limbic and
      prefrontal regions. Sex-by-diagnosis interactions were noted in the pattern of
      activation within the basal ganglia during incentive decision-making and within
      ventral prefrontal regions during facial affect processing. CONCLUSIONS:
      Potential sex-by-diagnosis interactions influencing the brain structural and
      functional correlates of disease expression in BD have received limited
      attention. Our data suggest that the sex of an individual modulates structure and
      function within subcortical and cortical regions implicated in disease
      expression.

PMID- 22631626
TI  - Combined oral midazolam-ketamine better than midazolam alone for sedation of
      young children: a randomized controlled trial.
AB  - BACKGROUND.  There is a lack of clinical trials on paediatric dental sedation.
      AIM.  We investigated whether young children's behaviour improves during dental
      treatment with oral ketamine/midazolam compared with midazolam alone or no
      sedation. DESIGN.  Healthy children under 36 months of age, presenting early
      childhood caries were randomly assigned to receive protective stabilization plus:
      combined oral midazolam (0.5 mg/kg) and ketamine (3 mg/kg) (MK), or oral
      midazolam (1.0 mg/kg) (MS), or no sedative (PS). One observer scored children's
      behaviour using the Ohio State University Behavior Rating Scale (OSUBRS) at
      determined points in a dental exam (no sedative) and treatment session. Data were
      analysed using nonparametric bivariate tests. RESULTS.  Forty-one children were
      included. In the dental exam session, the sum of OSUBRS scores was similar for
      the three groups (P = 0.81). In the treatment session, the MK produced more
      cooperative behaviour than MS and PS (P = 0.01), longer sessions (P = 0.04), and
      a pattern of homogeneous OSUBRS scores from the reception area (before sedative
      administration) to the end of the session (P = 0.06). No immediate and post
      discharge side effects were observed in groups MK and MS. CONCLUSIONS.  The
      combination of oral midazolam and ketamine is efficacious for guiding the
      behaviour of children under 3 years old.

PMID- 22631627
TI  - A novel HLA-A allele detected by sequence-based typing: A*11:01:18.
AB  - HLA-A*11:01:18 shows one nucleotide difference at genomic nt 331 G>A (codon 43
      CAG>CAA) in exon 2.

PMID- 22631628
TI  - Relationship between BMI, body image, and smoking in Korean women as determined
      by urine cotinine: results of a nationwide survey.
AB  - BACKGROUND: This study examined the influence of body mass index (BMI),
      subjective body perception (SBP), and the differences between BMI and SBP
      influence on smoking among women. METHODS: This study used the Korea National
      Health and Nutrition Examination Survey IV-2, 3 2008-2009. A urinary cotinine
      test was administered to 5485 women at least 19 years of age. Individuals whose
      cotinine level was at least 50 ng/mL were categorized as smokers. A multiple
      logistic regression analysis was performed to estimate the extent to which body
      related variables affect female smoking. RESULTS: Women with a lower BMI who
      perceived themselves to be normal or very fat were 2.09 times (1.14-3.83) more
      likely to smoke than women with a normal BMI and SBP. Women who were never
      married with a low BMI and thin SBP were 3.11 times (1.47-6.55) more likely to
      smoke than women with a normal BMI and SBP. Married women with a high BMI who
      considered themselves very fat were 0.63 times (0.43-0.94) less likely to smoke
      than women with a normal BMI and SBP. In contrast, divorced and widowed women
      with a low or normal BMI who considered themselves very fat were 26.1 times (1.35
      507.3) more likely to smoke. CONCLUSIONS: Discrepancies between the objective
      physical condition (BMI) and the subjective body image (SBP) influence the female
      smoking rate. To reduce the number of female smokers, public education on the
      association between smoking behavior and weight issues is needed, especially
      among women with low BMI and distorted weight perception.

PMID- 22631629
TI  - Mobile phone use does not discourage adolescent smoking in Japan.
AB  - OBJECTIVE: The possibility that smoking prevalence among junior and senior high
      school students may decrease with increasing mobile phone bill was reported by
      the mass media in Japan. We conducted a nationwide survey on adolescent smoking
      and mobile phone use in Japan in order to assess the hypothesis that mobile phone
      use has replaced smoking. METHODS: A total of 70 junior high schools (response
      rate; 71%), and 69 high schools (90%) from all over Japan responded to 2005
      survey. Students in the responding schools were asked to fill out an anonymous
      questionnaire about smoking behavior, mobile phone bill, and pocket money.
      Questionnaires were collected from 32,615 junior high school students and 48,707
      senior high school students. RESULTS: The smoking prevalence of students with
      high mobile phone bill was more likely to be high, and that of students who used
      mobile phones costing 10,000 yen and over per month was especially high. When
      "quitters" were defined as students who had tried smoking but were not smoking at
      the time of survey, the proportion of quitters decreased as the mobile phone bill
      increased. The proportion of students who had smoking friends increased with the
      increase in the mobile phone bill per month. CONCLUSION: The hypothesis that the
      decrease in smoking prevalence among Japanese adolescents that has been observed
      in recent years is due to a mobile phone use can be rejected.

PMID- 22631630
TI  - Prognosis and management for gallbladder cancer with hepatic invasion: long-term
      results of 139 patients from a single center in China.
AB  - OBJECTIVE: To improve the diagnosis of primary gallbladder carcinoma (GBC)
      with/without hepatic metastases by analyzing our experience of different GBC
      treatment in our patients. METHODS: A retrospective study was carried out to
      analyze the clinical data of the 139 patients with GBC who underwent hepatic
      resection in our unit from January 2003 to December 2007. Patients were divided
      into two groups according to whether they demonstrated hepatic invasion. Tumor
      presentation, surgical modes, and prognosis of each patient were retrospectively
      reviewed. Kaplan-Meier curves and log-rank tests were employed to compare the
      survival rates of those patients undergoing different surgical procedures.
      RESULTS: Of the 139 patients, 46 were men and 93 were women with the male to
      female ratio of 1:2.0. Their ages were ranged from 35 to 86 years with a mean age
      of 62.8+/-10.4 years. There were 73 patients complicated with hepatic invasion
      (group A), and no hepatic invasion occurred in the other 66 patients (group B).
      Compared with the group B, the patients with hepatic invasion suffered lower
      differentiation of tumor (p=0.000), more advanced Nevin staging (p=0.008) and
      poorer prognosis (p=0.013). Radical resection were more frequently performed in
      group B (75.76%) than in group A (45.20%) with better outcomes (p=0.000).
      CONCLUSION: GBC patients complicated with hepatic invasion had poorer prognosis
      than those without invasion in long-term follow-ups. Radical resection might
      result in a satisfied prognosis in patients without hepatic invasion, but appears
      less favorable than palliative resection in those who were complicated with
      hepatic invasion.

PMID- 22631631
TI  - Type-specific incidence and persistence of HPV infection among young women: a
      prospective study in North India.
AB  - BACKGROUND: Infections with human papillomavirus (HPV) are highly prevalent among
      sexually active young women in India. However, not much is known about the
      incidence of type-specific human papillomavirus (HPV) infections and their
      patterns of persistence, especially in the Indian context. OBJECTIVE: The
      objective of this study was to evaluate the rate of acquisition and persistence
      of HPV types in young women. METHODS: Women residing in an urban slum in Delhi
      (n=1300) were followed for 24 months at 6 monthly intervals. Exfoliated cervical
      cells collected at each visit were tested for the presence of HPV DNA. Genotyping
      was performed using the reverse line blot assay. RESULTS: The incidence rate for
      any HPV type was calculated to be 5 per 1000 women-months. Among high risk HPV
      types, HPV16 had the highest incidence rate followed by HPV59, HPV52 and HPV18,
      i.e., 3.0, 0.58, 0.41 and 0.35 women per 1000 women-months respectively. The
      persistence rate was higher for high-risk than low-risk HPV types. Among low-risk
      types, HPV42, HPV62, HPV84 and HPV89 were found to persist. Whereas almost all
      high risk types showed persistence, the highest rate was found in women with HPV
      types 16, 45, 67, 31, 51 and 59. The persistence rate for HPV16 infection was 45
      per 1000 women-months. CONCLUSION: Incident HPV infections and high risk HPV type
      specific persistence were found to be high in our study population of young
      married women. Understanding the patterns of HPV infection may help plan
      appropriate strategies for prevention programs including vaccination and
      screening.

PMID- 22631632
TI  - Killing effects of different physical factors on extracorporeal HepG2 human
      hepatoma cells.
AB  - OBJECTIVE: To determine the killing effects on extracorporeal HepG2 cells under
      different temperatures, pressures of permeability and lengths of treatment time.
      METHOD: According to different temperatures, pressures of permeability and
      lengths of treating time, extracorporeal HepG2 cells of human hepatoma cell-line
      were grouped to 80 groups. Cell index (CI) as the measurement of killing effect
      were calculated by monotetrazolium (MTT) methods, i.e., CI = 1 - (the OD value in
      treated group - the OD value in blank control group)/(mean of untreated control
      group - mean of blank control group). According to the factorial design, data
      were fed into SPSS 10.0 and analyzed by three-way ANOVA (analysis of variance).
      RESULT: Temperature, pressure of permeability and length of treating time all had
      effects on the CI (cell index) level. Length of treating time was the most
      influential factor of the three. Additionally, any two of them all had
      statistically significant interactive effects on the CI level. When treated for 5
      30 min, destilled water at 46 degrees C stably generated the highest CI.
      CONCLUSION: The "46 degrees C-destilled water-60 min" was considered as the
      optimal combination of conditions which lead to highest CI. We suggest exerting
      celiac lavage for 15 min with stilled water at 40 degrees C-43 degrees C in
      surgical practice as a hyperthermia treatment to achieve ideal killing effects on
      free cancer cells, which is feasible, practical, and clinically effective.

PMID- 22631633
TI  - Chemopreventive potential of an ethyl acetate fraction from Curcuma longa is
      associated with upregulation of p57(kip2) and Rad9 in the PC-3M prostate cancer
      cell line.
AB  - BACKGROUND: Turmeric (Curcuma longa) has been shown to possess anti-inflammatory,
      antioxidant and antitumor properties. However, despite the progress in research
      with C. longa, there is still a big lacuna in the information on the active
      principles and their molecular targets. More particularly very little is known
      about the role of cell cycle genes p57(kip2) and Rad9 during chemoprevention by
      turmeric and its derivatives especially in prostate cancer cell lines. METHODS:
      Accordingly, in this study, we have examined the antitumor effect of several
      extracts of C. longa rhizomes by successive fractionation in clonogenic assays
      using highly metastatic PC-3M prostate cancer cell line. RESULTS: A mixture of
      isopropyl alcohol: acetone: water: chloroform: and methanol extract of C. longa
      showed significant bioactivity. Further partition of this extract showed that
      bioactivity resides in the dichloromethane soluble fraction. Column
      chromatography of this fraction showed presence of biological activity only in
      ethyl acetate eluted fraction. HPLC, UV-Vis and Mass spectra studies showed
      presence three curcuminoids in this fraction besides few unidentified components.
      CONCLUSIONS: From these observations it was concluded that the ethyl acetate
      fraction showed not only inhibition of colony forming ability of PC-3M cells but
      also up-regulated cell cycle genes p57(kip2) and Rad9 and further reduced the
      migration and invasive ability of prostate cancer cells.

PMID- 22631634
TI  - Prospective study on the survival of HCC patients treated with transcatheter
      arterial lipiodol chemoembolization.
AB  - AIM: Tanscatheter arterial embolization irrespective of with or without an
      anticancer agent and lipiodol has been controversial with regard to survival
      benefit. Therefore, we conducted a prospective study to analyze the effect of
      transcatheter arterial lipiodol chemoembolization (TACE) on the survival of HCC.
      METHODS: A prospective study was conducted, and a total of 326 patients with
      primary liver cancer who were newly diagnosed were collected from January 2004 to
      January 2005 in Zhejiang Provincial People's Hospital of China. A univariate
      Cox's regression analysis was used to assess the survival of the HCC cases
      receiving TACE. RESULTS: The duration of follow-up for the HCC patients treated
      with TACE ranged from 3 months to 60 months. For the overall patients, survival
      rate at 5 years was 42%. Both HBV Ag and HCV Ab positive patients showed
      significantly low survival rate at 5 years. The multivariate analysis revealed
      The IV TNM stage was related to an heavy increased risk of death of HCC patients,
      and Child C grade group showed a significant moderate increased risk. CONCLUSION:
      Our study showed TACE is associated with a better prognosis of HCC patients, and
      the HBV infection, TNM stage, Child-Pugh grade and number of TACE may influence
      the survival probability. Further TACE studies should be assess the quality of
      life of HCC patients, so as to provide more information for treatment of HCC.

PMID- 22631635
TI  - Silencing of the COPS3 gene by siRNA reduces proliferation of lung cancer cells
      most likely via induction of cell cycle arrest and apoptosis.
AB  - The COPS3 gene has stimulating effect on cell proliferation and progression of
      osteosarcomas and related cells. However, the features of COPS3 and its potential
      application as a therapeutic target in other cancers has not yet been studied. In
      this study, therefore, the effect of COPS3 silencing via COPS3 siRNA on lung
      cancer cell proliferation was examined. Expression levels of COPS3 gene in COPS3
      siRNA infected cells and control siRNA infected cells were compared with real
      time PCR and Western blot analysis. Cell proliferation levels were
      comprehensively analyzed by MTT, BrdU incorporationy, and colony formation
      assays. For mechanistic assessment the effects of COPS3 silencing on cell cycle
      and apoptosis were analyzed using flow cytometry. Results showed that successful
      silencing of the COPS3 gene at both translational and transcriptional levels
      significantly reduced the proliferation and colony formation by lung cancer cells
      (p<0.01). Flow cytometry showed cell cycle arrest in the G0/G1 phase after COPS3
      silencing, and more importantly, apoptosis was induced as a result of COPS3
      knockdown, which negatively affected cell survival. Therefore, these results
      provide another piece of important evidence that the COPS3 gene expressed in lung
      cancer cells may play a critical role in stimulating proliferation. Down
      regulation of COPS3 could significantly inhibit lung cancer cell growth, which
      was most likely mediated via induction of cell cycle arrest in G0/G1 phase and
      apoptosis.

PMID- 22631636
TI  - Expression and prognostic value of matrix metalloproteinase-7 in colorectal
      cancer.
AB  - The purpose of this study was to evaluate expression and prognostic value of
      matrix metalloproteinase-7 (MMP-7) in colorectal cancer (CRC) patients. CRC
      tissues and corresponding distal normal mucosa tissues of 118 CRC patients were
      assessed by immunohistochemistry. Correlations between MMP-7 expression,
      patients' clinic pathological features, and overall survival rate were analyzed.
      We found that positive expression of MMP- 7 in CRC tissues was significantly
      higher than that in distal normal mucosa (61.0% vs. 39.8%, p=0.001). Poor
      histological differentiation, advanced clinical stage and lymph node metastasis
      were significantly correlated with MMP-7 expression in CRC. The overall survival
      rate was significantly higher in the MMP-7 negative group than the positive group
      (Log-rank test=9.957, p=0.002). MMP-7 appeared as a significant independent
      prognostic factor through multivariate survival analysis. Collectively, we found
      MMP-7 expression to be correlated with progression and metastasis of CRC and thus
      could be used as a predictive marker of prognosis in CRC patients.

PMID- 22631637
TI  - Activating transcription factor 1 is a prognostic marker of colorectal cancer.
AB  - OBJECTIVE: Identifying cancer-related genes or proteins is critical in preventing
      and controlling colorectal cancer (CRC). This study was to investigate the
      clinicopathological and prognostic value of activating transcription factor 1
      (ATF1) in CRC. METHODS: Protein expression of ATF1 was detected using
      immunohistochemistry in 66 CRC tissues. Clinicopathological association of ATF1
      in CRC was analyzed with chi-square test or Fisher's exact test. The prognostic
      value of ATF1 in CRC is estimated using the Kaplan-Meier analysis and Cox
      regression models. RESULTS: The ATF1 protein expression was significantly lower
      in tumor tissues than corresponding normal tissues (51.5% and 71.1%,
      respectively, P = 0.038). No correlation was found between ATF1 expression and
      the investigated clinicopathological parameters, including gender, age, depth of
      invasion, lymph node status, metastasis, pathological stage, vascular tumoral
      emboli, peritumoral deposits, chemotherapy and original tumor site (all with P >
      0.05). Patients with higher ATF1 expression levels have a significantly higher
      survival rate than that with lower expression (P = 0.026 for overall survival, P
      = 0.008 for progress free survival). Multivariate Cox regression model revealed
      that ATF1 expression and depth of invasion were the predictors of the overall
      survival (P = 0.008 and P = 0.028) and progress free survival (P = 0.002 and P =
      0.005) in CRC. CONCLUSIONS: Higher ATF1 expression is a predictor of a favorable
      outcome for the overall survival and progress free survival in CRC.

PMID- 22631638
TI  - Prognostic factors for overall survival in patients with metastatic colorectal
      carcinoma treated with vascular endothelial growth factor-targeting agents.
AB  - OBJECTIVE: Angiogenesis represents a key element in the pathogenesis of
      malignancy. There are no robust data on prognostic factors for overall survival
      (OS) in patients with metastatic colorectal cancer treated with vascular
      endothelial growth factor (VEGF)-targeted therapy. The present study was
      conducted to establish a prognostic model for patients using an oxaliplatin-based
      or irinotecan-based chemotherapy plus bevacizumab in metastatic colorectal
      cancer. METHODS: Baseline characteristics and outcomes on 170 patients treated
      with FOLFIRI or XELOX plus anti-VEGF therapy-naive metastatic colorectal cancer
      were collected from three Turkey cancer centers. Cox proportional hazards
      regression was used to identify independent prognostic factors for OS. RESULTS:
      The median OS for the whole cohort was 19 months (95% CI, 14.3 to 23.6 months).
      Three of the seven adverse prognostic factors according to the Anatolian Society
      of Medical Oncology (ASMO) were independent predictors of short survival: serum
      lactate dehydrogenase (LDH) greater than the upper limit of normal (ULN;
      p<0.001); neutrophils greater than the ULN (p<0.0014); and progression free
      survival (PFS) less than 6 months (p =0.001). CONCLUSION: Serum LDH and
      neutrophil levels were the main prognostic factors in predicting survival,
      followed by PFS. This model validates incorporation of components of the ASMO
      model into patient care and clinical trials that use VEGF-targeting agents.

PMID- 22631639
TI  - Trends in incidence of hepatocellular carcinoma, 1990-2009, Khon Kaen, Thailand.
AB  - BACKGROUND: Liver cancer is the most frequent cancer among Thais especially
      people in northeastern Thailand, but there has as yet been no assessment of
      trend. The data of all cancers in Khon Kaen can be retrieved from data base of
      the Khon Kaen Cancer Registry (KKCR) which was established in 1984. OBJECTIVE: To
      assess the incidence trend of hepatocellular carcinoma in Khon Kaen, Thailand,
      between 1990 and 2009. METHODS: Population-based cases of liver cancer registered
      between 1985 and 2009 were retrieved from the KKCR data base and cases with
      diagnosis of hepatocellular carcinoma (HCC) with the coding C22.0 according to
      ICD-O were selected. Incidence trends were calculated using the Jointpoint
      analysis. RESULTS: There were 7,859 cases of HCC during the study period. Males
      were affected two times more frequently than females. The most common age group
      of cases was 50 and 69 years (60.3%). Most patients were diagnosed based on
      radiology imaging (40.6%) while the morphology verification was 7%. The age
      standardized rates (ASR) were 13.1 to 49.8 per 100,000 among males and 4.8 to
      38.4 per 100,000 among females depending on year of diagnosis since 1985.
      Remarkably, the ASRs were clearly low during first few years of starting the
      registration. The overall ASRs of HCC were 30.3 per 100,000 in males (95% CI:
      25.9 to 34.6) and 13.1 per 100,000 (95% CI: 10.4 to 15.8) in females. During 1990
      2009, the trends in incidences have been decreasing significantly with the annual
      percent change (APC) of 6.2% per year (95% CI: -7.6 to -4.8) in males and by 6.5%
      per year in females (95% CI: -8.4 to -4.9). CONCLUSIONS: The incidence trends
      have been decreasing in both sexes. The recent decline in incidence may represent
      a falling risk.

PMID- 22631640
TI  - Improving quality of life among cancer patients in Malaysia.
AB  - There are an almost infinite number of states of health, all with differing
      qualities that can be affected by many factors. Each aspect of health has many
      components which contribute to multidimensionality. Cancer and its' related
      issues surrounding the treatment plan contribute to the variety of changes of
      quality of life of cancer patients throughout their life. The objective of this
      article was to provide an overview of some of the issues that can affect their
      quality of life and initiatives towards successful care in Malaysia by reviewing
      relevant reports and articles. The current strategies can be further strengthened
      by prevention of cancer while improving quality of service to cancer patients.

PMID- 22631641
TI  - N-nitrosodimethylamine in the Kashmiri diet and possible roles in the high
      incidence of gastrointestinal cancers.
AB  - The Kashmiri population is culturally distinct with special dietary features
      owing to the temperate climatic conditions of Kashmir valley. This has habituated
      the population to preserve food in smoked, pickled and sundried forms which
      include considerable amounts of N-nitroso compounds (NOCs). These are known to
      cause cytotoxicity, DNA damage, mutation, unscheduled DNA synthesis and DNA
      methylation. All of these changes at molecular level are known to contribute to
      the pathogenesis of cancer. One of the prominent NOCs found in Kashmiri food is N
      Nitrosodimethylamine (NDMA). Here we review the occurrence of NDMA in sundried
      foods, dried fish, kehwa, traditional pickle, Brassica oleracia and tobbaco. We
      also discuss its possible role in the high prevalence of gastrointestinal cancers
      in Kashmir.

PMID- 22631642
TI  - Risk factors of hepatocellular carcinoma--current status and perspectives.
AB  - Hepatocellular carcinoma is a common disorder worldwide which ranks 5th and 7th
      most common cancer among men and women. In recent years, different incidence
      trends have been observed in various regions, but the reasons are not completely
      understood. However, due to the great public efforts in HCC prevention and
      alternation of lifestyle, the roles of some well documented risk factors played
      in hepatocarcinogenesis might have changed. This paper summarizes both the
      environmental and host related risk factors of hepatocellular carcinoma including
      well established risk factors such as hepatitis virus infection, aflatoxin and
      alcohol, as well as possible risk factors such as coffee drinking and other
      dietary agents.

PMID- 22631643
TI  - Knockdown of radixin by RNA interference suppresses the growth of human
      pancreatic cancer cells in vitro and in vivo.
AB  - Radixin, encoded by a gene on chromosome 11, plays important roles in cell
      motility, invasion and tumor progression. However, its function in pancreatic
      cancer remains elusive. In this study, radixin gene expression was suppressed
      with a lentivirus-mediated short-hairpin RNA (shRNA) method. We found that
      radixin shRNA caused down-regulation of radixin in PANC-1 cells, associated with
      inhibition of pancreatic cancer cell proliferation, survival, adhesion and
      invasive potential in vitro. When radixin-silenced cells were implanted in nude
      mice, tumor growth and microvessel density were significantly inhibited as
      compared to blank control cells or nonsense shRNA control cells. Thrombospondin-1
      (TSP-1) and E-cadherin were up-regulated in radixin-silenced PANC-1 cells. Our
      results suggest that radixin might play a critical role in pancreatic cancer
      progression, possibly through involvement of down-regulation of TSP-1 and E
      cadherin expression.

PMID- 22631644
TI  - Identification of a cancer stem-like population in the Lewis lung cancer cell
      line.
AB  - OBJECTIVE: Although various human cancer stem cells (CSCs) have been defined,
      their applications are restricted to immunocompromised models. Developing a novel
      CSC model which could be used in immunocompetent or transgenic mice is essential
      for further understanding of the biomolecular characteristics of tumor stem
      cells. Therefore, in this study, we analyzed murine lung cancer cells for the
      presence of CSCs. METHODS: Side population (SP) cells were isolated by
      fluorescence activated cell sorting, followed by serum-free medium (SFM) culture,
      using Lewis lung carcinoma cell (LLC) line. The self-renewal, differentiated
      progeny, chemosensitivity, and tumorigenic properties in SP and non-SP cells were
      investigated through in vitro culture and in vivo serial transplantation.
      Differential expression profiles of stem cell markers were examined by RT-PCR.
      RESULTS: The SP cell fraction comprised 1.1% of the total LLC population. SP
      cells were available to grow in SFM, and had significantly enhanced capacity for
      cell proliferation and colony formation. They were also more resistant to
      cisplatin in comparison to non-SP cells, and displayed increased tumorigenic
      ability. Moreover, SP cells showed higher mRNA expression of Oct-4, ABCG2, and
      CD44. CONCLUSION: We identified SP cells from a murine lung carcinoma, which
      possess well-known characteristics of CSCs. Our study established a useful model
      that should allow investigation of the biological features and
      pharmacosensitivity of lung CSCs, both in vitro and in syngeneic immunocompetent
      or transgenic/knockout mice.

PMID- 22631645
TI  - Transcriptome network analysis reveals potential candidate genes for esophageal
      squamous cell carcinoma.
AB  - The esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with a poor
      prognosis. Understanding molecular changes in ESCC should improve identification
      of risk factors with different molecular subtypes and provide potential targets
      for early detection and therapy. Our study aimed to obtain a molecular signature
      of ESCC through the regulation network based on differentially expressed genes
      (DEGs). We used the GSE23400 series to identify potential genes related to ESCC.
      Based on bioinformatics we constructed a regulation network. From the results, we
      could establish that many transcription factors and pathways closely related with
      ESCC were linked by our method. STAT1 also arose as a hub node in our
      transcriptome network, along with some transcription factors like CCNB1, TAP1,
      RARG and IFITM1 proven to be related with ESCC by previous studies. In
      conclusion, our regulation network provided information on important genes which
      might be useful in investigating the complex interacting mechanisms underlying
      the disease.

PMID- 22631646
TI  - Assessment of 8-isoprostane (8-isoPGF2alpha) in urine of non- small cell lung
      cancer (NSCLC) patients undergoing chemotherapy.
AB  - 8-Isoprostane (8-isoPGF2alpha) is a reliable marker and considered a gold
      standard for lipid peroxidation. There are very few reports of 8-isoprostane
      levels in cancer patients, and in patients undergoing chemotherapy. Oxidative
      stress is however expected and has been observed in patients with cancer. This
      study measured 8-isoprostane levels in urine by ELISA of 25 patients undergoing
      chemotherapy for advanced non-small cell lung cancer, at cycles 1, 2, and 3 of
      treatment. It considers the creatinine clearance of the patients, and correction
      of 8-isoprostane levels by creatinine clearance, and overnight urine volume
      methods. The average 8-isoprostane levels in urine increased more than 6 to 12
      fold on chemotherapy treatment, from 532+/-587 pg/mL at cycle 1, 6181+/-4334 at
      cycle 2, and 5511+/-2055 at cycle 3. Similar results were obtained if 8
      isoprostane levels were corrected for overnight urine volume, giving averages of
      285+/-244 MUg at cycle 1, 4122+/-3349 at cycle 2, and 3266+/-1200 at cycle 3. No
      significant difference was seen in average total overnight urine volume or number
      of urinations between chemotherapy cycles except for a large variation in urine
      volume between cycle 2 and 3. Creatinine levels were significantly different only
      between cycles 1 and 2 (p=0.016). In conclusion, cisplatin therapy has been shown
      to induce high levels of lipid peroxidation in lung cancer patients and can be
      assessed from the 8-isoprostane marker in overnight urine, with or without urine
      volume correction.

PMID- 22631647
TI  - Adenovirus-mediated double suicide gene selectively kills gastric cancer cells.
AB  - The aim of this study was to evaluate the effect of the adenovirus-mediated
      double suicide gene (CD/TK) for selective killing of gastric cancer cells.
      Gastric cancer cells SCG7901 and normal gastric epithelial cell lines were
      infected by adenoviruses Ad-survivin/GFP and Ad-survivin/CD/TK. GFP expression
      and CD-TK were detected by fluorescence microscopy and reverse transcriptase
      polymerase chain reaction (RT-PCR), respectively. After treatment of the infected
      cells with the pro-drugs ganciclovir (GCV) and/or 5-FC, the cell growth status
      was evaluated by methyl thiazolyl tetrazolium assay. Cell cycle changes were
      detected using flow cytometry. In nude mice bearing human gastric cancer, the
      recombinant adenovirus vector was injected directly into the tumor followed by an
      intraperitoneal injection of GCV and/or 5-FC. The subsequent tumor growth was
      then observed. The GFP gene driven by survivin could be expressed within the
      gastric cancer line SCG7901, but not in normal gastric epithelial cells. RT-PCR
      demonstrated the presence of the CD/TK gene product in the infected SCG7901
      cells, but not in the infected normal gastric epithelial cells. The infected
      gastric cancer SCG7901, but not the gastric cells, was highly sensitive to the
      pro-drugs. The CD/TK fusion gene system showed significantly greater efficiency
      than either of the single suicide genes in killing the target cells (P<0.01).
      Treatment of the infected cells with the pro-drugs resulted in increased cell
      percentage in G0-Gl phase and decreased percentage in S phase. In nude mice
      bearing SCG7901 cells, treatment with the double suicide gene system
      significantly inhibited tumor growth, showing much stronger effects than either
      of the single suicide genes (P<0.01). The adenovirus-mediated CD/TK double
      suicide gene driven by survivin promoter combined with GCV an 5-FC treatment
      could be an effective therapy against experimental gastric cancer with much
      greater efficacy than the single suicide gene CD/TK combined with GCV or 5-FC.

PMID- 22631648
TI  - Concurrent weekly docetaxel chemotherapy in combination with radiotherapy for
      stage III and IVA-B nasopharyngeal carcinoma.
AB  - BACKGROUND AND PURPOSE: Cisplatin is the most common chemotherapeutic agent for
      loco-regionally advanced nasopharyngeal carcinoma (NPC); however, toxicity is a
      limiting factor for some patients. We retrospectively compared the efficacy and
      toxicity of weekly docetaxel-based and cisplatin-based concurrent
      chemoradiotherapy in loco-regionally advanced NPC. METHODS AND MATERIALS: Eighty
      four patients with Stage III and IVA-B NPCs, treated between 2007 and 2008, were
      retrospectively analyzed. Thirty received weekly docetaxel-based concurrent
      chemotherapy, and 43 were given weekly cisplatin-based concurrent chemotherapy.
      Radiotherapy was administered using a conventional technique (seven weeks, 2.0 Gy
      per fraction, total dose 70-74 Gy) with 6-8 Gy boosts for some patients with
      locally advanced disease. RESULTS: Median follow-up time was 42.3 months (range,
      8.6-50.8 months). There were no significant differences in the 3-year loco
      regional failure-free survival (85.6% vs. 92.3%; p=0.264), distant failure-free
      survival (87.0% vs. 92.5%; p=0.171), progression-free survival (85.7% vs. 88.4%;
      p=0.411) or overall survival (86.5% vs. 92.5%, p=0.298) of patients treated
      concurrently with docetaxel or cisplatin. Severe toxicity was not common in
      either group. CONCLUSIONS: Weekly docetaxel-based concurrent chemoradiotherapy is
      potentially effective and has a tolerable toxicity; however, further
      investigations are required to determine if docetaxel is superior to cisplatin
      for advanced stage NPC.

PMID- 22631649
TI  - Survival rates of breast cancer: a hospital-based study from northeast of
      Thailand.
AB  - A retrospective cohort study was carried out with 340 female breast cancer at a
      teaching university in northeast of Thailand recruited and followed-up until the
      end of 2006. Survival probabilities were estimated using the Kaplan-Meier method.
      161 cases were alive after five years and 58 patients were lost to follow-up. The
      overall observed survival rates at 1, 3 and 5 years were 83.3%, 59.9% and 42.9%,
      respectively. When analysis was conducted for stage combined into 2 groups, early
      (stage I, II and unknown) and late (stage III and IV), the 5-year survival rate
      for early stage (60%; 95%CI: 0.51-0.67), was higher than for late stage (27%;
      95%CI: 0.19-0.34) with high statistical significance (p<0.001). The hazard ratio
      of patients with stage IV was 11.6 times greater than for stage I (p=0.03). The
      findings indicate that the different stages of breast cancer markedly effect the
      overall survival rate.

PMID- 22631650
TI  - Effect of self-efficacy on Turkish children's perceptions of the
      advantages/disadvantages of smoking.
AB  - OBJECTIVE: This descriptive, cross sectional study was conducted to examine the
      effect of levels of self-efficacy on children's perceptions of pros and cons of
      smoking. METHODOLOGY: The sample was 233 fifth-grade students. Data were
      collected in September 2010 using the Socio-Demographic Data Collection Form,
      Self Efficacy Scale Child Form and Child Decision Balance Scale and analyzed via
      percentage calculations and t test with the SPSS 11.00 statistical package
      program. RESULTS: Average age of the students participating in the research was
      11.1+/-0.41, 49.8% (n: 116) being female and 50.2% (n:117) male. The difference
      between the score averages of the pros of smoking perceptions of children with a
      high self-efficacy level and of those with a low self efficacy level (t=2.117,
      p=.042) and the difference between the score averages of the cons of smoking
      perceptions of children with a high self-efficacy level and of those with a low
      self-efficacy level (t=2.206, p=.035) were found to be statistically significant.
      CONCLUSIONS: Children's positive perceptions of smoking were low and negative
      perceptions high when their self efficacy levels were high. Conversely,
      children's positive perceptions of smoking were high when their self efficacy
      levels were low.

PMID- 22631651
TI  - Prevalence of human papillomavirus and co-existent sexually transmitted
      infections among female sex workers, men having sex with men and injectable drug
      abusers from eastern India.
AB  - BACKGROUND: Human papillomavirus (HPV) is a very common sexually transmitted
      disease affecting both men and women and is responsible for different ano-genital
      cancers in either sex. Co-existing sexually transmitted infections (STI)
      including HIV have been considered as important co-factors for carcinogenesis
      induced by HPV. The purpose of this study was to determine the prevalence of any
      HPV, HPV 16 and HPV 18 and also concomitant STIs among female sex workers (FSW),
      men having sex with men (MSM) and injectable drug users (IDU). MATERIAL AND
      METHOD: This cross-sectional study was conducted among 45 FSWs, 26 MSMs and 58
      IDUs who attended the STI or de-addiction clinics. Genital scrape samples
      collected from glans penis and coronal sulcus in males and cervical squamo
      columnar junction in females were tested for HPV DNA by PCR using HPV L1
      consensus primer. Type specific PCR to detect HPV 16 and 18 was done on the
      samples positive on consensus PCR. All participants were tested for associated
      STIs including HIV and hepatitis B and cervical cytology was done on all females.
      RESULTS: Among the FSWs, HPV was detected in 73.3% and HPV 16 and 18 was detected
      in 25.7%. Though the HPV prevalence was similarly high among MSMs (69.2%) and
      IDUs (72.4%), the prevalence of HPV 16 and 18 was much lower in these groups
      compared to the FSWs. Prevalence of cervico-vaginal infection with Trichomonas
      vaginalis and syphilis was significantly higher in the HPV positive women
      compared to the HPV negative women. There was no statistically significant
      difference in the prevalence of other STIs among HPV positive and negative women
      and men. CONCLUSION: HPV infection is highly prevalent among FSW, MSM and IDUs.
      Trichomonas vaginalis infection is more frequent in HPV positive women.

PMID- 22631652
TI  - Efficacy analysis of simplified intensity-modulated radiotherapy with high or
      conventional dose and concurrent chemotherapy for patients with neck and upper
      thoracic esophageal carcinoma.
AB  - For patients with neck and upper thoracic esophageal carcinoma, it is difficult
      to control lymph node metastases with conventional dose therapy. In this study,
      we assessed the feasibility of simplified intensity-modulated radiotherapy
      (sIMRT) and concurrent chemotherapy for 44 patients and boosted high-dose to
      metastatic lymph nodes.Three radiation treatment volumes were defined: PGTVnd,
      with which 68.1 Gy was delivered in high dose group (hsIMRT group), and 60 Gy in
      the conventional dose group (csIMRT group); PTV1, featuring 63.9 Gy in the hsIMRT
      group and 60Gy in the csIMRT group; PTV2, with 54 Gy given to both groups. The
      sIMRT plan included 5 equi-angular coplanar beams. All patients received the
      cisplatin and 5-FU regimen concurrently with radiotherapy. The treatment was
      completed within six weeks and one case with grade three acute bronchitis was
      observed in hsIMRT group. For esophageal lesions, 80% complete response (CR) and
      20% partial response (PR) rates were found in the hsIMRT group, and 79.2% CR,
      with 20.8% PR, in the csIMRT group; for lymph node lesions, 75% CR and 25% PR
      rates were observed in the hsIMRT group, with 45.8% and 37.5% respectively in the
      csIMRT group (P <0.05). The differences in 1-, 2- and 3-year relapse-free
      survival rates were all statistically significant (P <0.05). The major toxicity
      observed in both groups was Grade I~II leucopenia. sIMRT can generate a desirable
      dose distribution in treatment of neck and upper thoracic esophageal carcinoma
      with a better short-term efficacy. Boosted high dosing to metastatic lymph nodes
      can increase the relapse-free survival rate.

PMID- 22631653
TI  - Breast cancer scenario in a regional cancer centre in Eastern India over eight
      years--still a major public health problem.
AB  - In spite of screening and early diagnostic tests, the upward trend of breast
      cancer has become a matter of great concern in both developed and developing
      countries. The data collected by Population Based Cancer Registry in Chittaranjan
      National Cancer Institute, a regional cancer centre in Kolkata, from 1997 to 2004
      gives an insight about the scenario of breast cancer in this part of Eastern
      India. The total no of female breast cancer cases were steadily increasing from
      1997 to 2001 and only slightly lower from 2002 to 2004. and majority were in the
      40-49 year old age group during this period. The next most commonly affected age
      group was 50-59 years. Regarding the distribution according to treatment, the
      main modality was surgery and radiotherapy followed by combined surgery,
      chemotherapy and radiotherapy and then combined surgery and chemotherapy. The
      commonest type was ductal followed by lobular cancer. In this eight year study in
      CNCI, status of patients on last day of the respective year was assessed. Number
      of patients alive was 43.5% in 1997. The percentage gradually increased up to
      2000 and then gradually decreased to 47.4% in 2004. Also with every passing year,
      percentage mortality gradually decreased from 25.7% in 1997 to 16.8% in 2004.
      Better pattern of care (diagnosis and treatment) was reflected in this picture.
      However, lost to follow up, which also implies non compliance to treatment,
      increased to 30.8% in 1997 to 35.8% in 2004. Due to the small number of male
      breast cancers, only female cases were considered. In conclusion, breast cancer
      continues to be a major problem in Kolkata, India.

PMID- 22631654
TI  - Meta-analysis of the association between GSTM1 and GSTT1 gene polymorphisms and
      cervical cancer.
AB  - AIM: We conducted a meta-analysis to analyze the influence of GSTM1 and GSTT1
      gene polymorphisms on cervical cancer risk, and explore gene-environment
      interactions. METHODS: Identification of relevant studies was carried out through
      a search of Medline and the EMbase up to Oct. 2011. All case-control studies that
      investigated the association between GSTM1 and GSTT1 gene polymorphisms and risk
      of cervical cancer were included. The pooled odds ratio (OR) was used for
      analyses of results and the corresponding 95% confidence intervals (CI) were
      estimated. RESULTS: A total of 21 case-control studies were included in the meta
      analysis of GSTM1 (2,378 cases and 2,639 controls) and GSTT1 (1,229 cases and
      1,223 controls) genotypes. The overall results showed that the GSTM1 null was
      related to an increased risk of cervical cancer (OR=1.50, 95% CI=1.21-1.85).
      Subgroup analysis were performed based on smoking and ethnicity. Our results
      showed that smokers with null GSTM1 genotype had a moderate increased risk of
      cervical cancer (OR=1.85, 95% CI=1.07-3.20). For the ethnicity stratification,
      moderate significantly increased risk of null GSTM1 genotype was found in Chinese
      (OR=2.12, 95% CI=1.43-3.15) and Indian populations (OR=2.07, 95% CI=1.49-2.88),
      but no increased risk was noted in others. CONCLUSION: This meta-analysis
      provided strong evidence that the GSTM1 genotype is associated with the
      development of cervical cancer, especially in smokers, and Chinese and Indian
      populations. However, no association was found for GSTT1 null genotype carriers.

PMID- 22631655
TI  - Role of centromere protein H and Ki67 in relapse-free survival of patients after
      primary surgery for hypopharyngeal cancer.
AB  - PURPOSE: Centromere protein H (CENP-H) and Ki67 are overexpressed in some
      malignancies, but whether they are predictors of survival after primary resection
      for hypopharyngeal squamous cell carcinoma (HSCC) remains unknown. METHODS: We
      assessed immunohistochemical expression of CENP-H and Ki67 in 112 HSCC specimens
      collected between March 2003 and March 2005 for analysis by clinical
      characteristics. The Kaplan-Meier method was used to analyze relapse-free
      survival and logistic multivariate regression to determine risk factors of
      relapse-free survival. Cholecystokinin octapeptide assays and flow cytometry were
      used to examine cell proliferation and apoptosis after siRNA inhibition of CENP-H
      in HSCC cells. RESULTS: Overall, 50 (44.6%) HSCC specimens showed upregulated
      CENP-H expression and 69 (61.6%) upregulated Ki67. An increased CENP-H protein
      level was associated with advanced cancer stage and alcohol history (P=0.012 and
      P=0.048, respectively) but an increased Ki67 protein level only with advanced
      cancer stage (P=0.021). Increased CENP-H or Ki67 were associated with short
      relapse-free survival (P<0.001 or P=0.009, respectively) and were independent
      predictors of relapse-free survival (P=0.001 and P=0.018, respectively). siRNA
      knockdown of CENP-H mRNA inhibited cell proliferation and promoted cancer cell
      apoptosis in vitro. CONCLUSIONS: Upregulated CENP-H and Ki67 levels are
      significantly associated with short relapse-free survival in HSCC. These factors
      may be predictors of a relapsing phenotype in HSSC cases.

PMID- 22631656
TI  - Comorbidity relationship to outcome of radical cystectomy in Chinese: a single
      institution study with the ACE-27 comorbidity index.
AB  - To determine the relationship between comorbidity and outcome after radical
      cystectomy in Chinese patients by using the Adult Comorbidity Evaluation (ACE)-27
      index. Two-hundred-and-forty-six patients treated with radical cystectomy at the
      Second Xiangya Hospital of Central South University, Hunan Province, China
      between 2000 and 2010 were retrospectively analyzed. Medical records were
      reviewed for age, gender, delayed time of radical cystectomy, urinary diversion
      type, pelvic lymphadenectomy status, TNM stage, and pathological grade.
      Comorbidity information was assessed by the ACE-27 index. The outcome measurement
      was overall survival. Univariate and multivariate Cox proportional hazards
      regression analyses were used to determine the association between comorbidity
      and outcome. The study population consisted of 215 (87.40%) males and 31 (12.60%)
      females with a mean age of 62+/-11 years. Median duration of follow-up was 47+/
      31 months. A total of 151 (61.38%) patents died during follow-up. Of those, 118
      (47.97%) had at least one comorbidity. According to the ACE-27 scores, 128
      (52.03%) patients had no comorbidity, 79 (32.11%) had mild, 33 (13.41%) had
      moderate, and 6 (2.45%) had severe comorbidities. Multivariate analysis indicated
      that moderate (p=0.002) and severe (p<0.001) comorbidity was significantly
      associated with decreased overall survival. In addition, age >=70 years
      (p=0.002), delayed time of radical cystectomy >12 weeks (p=0.044), pelvic
      lymphadenectomy status (p=0.014), and TNM stage >T3 (p<0.001) were determined to
      be independent risk factors of overall survival. Increasing severity of
      comorbidity statistically correlated with decreased overall survival after
      radical cystectomy.

PMID- 22631657
TI  - Epidemiology of esophageal cancer in Kazakhstan.
AB  - The incidence of esophageal cancer in Kazakhstan was analysed for the period of
      1989-2010 years, with a focus on trends by age, gender and region. The highest
      rates of incidence were evident in the Western regions. The dynamics for cancer
      of the esophagus in the Republic demonstrated decrease, except in the Karaganda
      region, where a tendency for increase was noted. Considerable variation between
      regions pointed to differences in risk factor exposure which need to be targeted
      for future control efforts.

PMID- 22631658
TI  - CYP2W1, CYP4F11 and CYP8A1 polymorphisms and interaction of CYP2W1 genotypes with
      risk factors in Mexican women with breast cancer.
AB  - Breast cancer (BCa) is the leading type of cancer in Mexican women. Genetic
      factors, such as single nucleotide polymorphisms (SNP) of P450 system, have been
      reported in BCa. In this report, and for the first time in the literature, we
      analyzed the rs3735684 (7021 G>A), rs11553651 (15016 G>T) and rs56195291 (60020
      C>G) polymorphisms in the CYP2W1, 4F11 and 8A1 genes in patients with BCa and in
      healthy Mexican women to identify a potential association between these
      polymorphisms and BCa risk. Patients and controls were used for polymorphism
      analysis using an allelic discrimination assay with TaqMan probes and confirmed
      by DNA sequencing. Links with clinic-pathological characteristics were also
      analyzed. Statistical analysis was performed using the standard chi2 or Fisher
      exact test statistic. No significant differences were observed in the
      distributions of CYP2W1 (OR 8.6, 95%CI 0.43-172.5 P>0.05; OR 2.0, 95%CI 0.76-5.4,
      P>0.05) and CYP4F11 (OR 0.3, 95%CI 0.01-8.4 P>0.05) genotypes between the
      patients and controls. Only the CYP8A1 CC genotype was detected in patients with
      BCa and the controls. All polymorphism frequencies were in Hardy-Weinberg
      Equilibrium (HWE) in the controls (P>0.05). We found a significant association
      between BCa risk and smoking, use of oral contraceptives or hormonal replacement
      therapy (HRT), obesity, hyperglycemia, chronic diseases, family history of cancer
      and menopausal status in the population studied (P<0.05). Tobacco, oral
      contraceptive or HRT, chronic diseases and obesity or overweight were strongly
      associated with almost eight, thirty-five, nine and five-fold increased risk for
      BCa. Tobaco, obesity and hyperglycemia significantly increased the risk of BCa in
      the patients carrying variant genotypes of CYP2W1 (P<0.05). These results
      indicate that the CYP2W1 rs3735684, CYP4F11 rs11553651 and CYP8A1 rs56195291 SNPs
      are not a key risk factor for BCa in Mexican women. This study did not detect an
      association between the CYP2W1, 4F11 and 8A1 genes polymorphisms and BCa risk in
      a Mexican population. However, some clinico-pathological risk factors interact
      with CYP2W1 genotypes and modifies susceptibility to BCa.

PMID- 22631659
TI  - Expression of tumor necrosis factor-alpha-induced protein 8 in pancreas tissues
      and its correlation with epithelial growth factor receptor levels.
AB  - Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) is a
      recently identified protein considered to be associated with carcinogenesis. To
      investigate its expression pattern in pancreatic cancer patients and to analyse
      its correlation with clinicopathological significance and the expression levels
      of epithelial growth factor receptor (EGFR), immunohistochemistry was performed
      to detect the TNFAIP8 and EGFR proteins in pancreatic cancers, pancreatitis
      tissues, and healthy controls. The results showed stronger staining of TNFAIP8
      protein in pancreatic cancer tissues compared with normal pancreas tissue.
      Furthermore, in 56 patients with pancreatic cancer, the expression levels of
      TNFAIP8 in patients with low tumor stage was higher than that with high tumor
      stage, and correlated with tumor staging and lymph node metastasis (P<0.05).
      Furthermore, TNFAIP8 expression positively correlated with EGFR levels
      (r=0.671135, P<0.05). These results indicate that TNFAIP8 may play important
      roles in the progression of pancreatic cancer.

PMID- 22631660
TI  - Genetic variants of NBS1 predict clinical outcome of platinum-based chemotherapy
      in advanced non-small cell lung cancer in Chinese.
AB  - OBJECTIVE: NBS1 plays a key role in the repair of DNA double-strand break (DSB).
      We conducted this study to investigate the effect of two critical polymorphisms
      (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of
      advanced non-small cell lung cancer (NSCLC) patients with platinum-based
      chemotherapy. METHODS: Using TaqMan methods, we genotyped the two polymorphisms
      in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals
      (CIs) were calculated as a measure of difference in the response rate of platinum
      based chemotherapy using logistic regression analysis. The Kaplan-Meier and log
      rank tests were used to assess the differences in progression-free survival (PFS)
      and overall survival (OS). Cox proportional hazards model was applied to assess
      the hazard ratios (HRs) for PFS and OS. RESULTS: Neither of the two polymorphisms
      was significantly associated with treatment response of platinum-based
      chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a
      significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0
      months, P = 0.040). Multivariable cox regression analysis further showed that
      rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG:
      Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI:
      0.32-0.97). Similarly, rs13312840 with a small sample size also showed a
      significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53
      428.39). CONCLUSIONS: Our findings suggest that NBS1 polymorphisms may be genetic
      biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in
      the Chinese population.

PMID- 22631661
TI  - Relationships among serum CA15-3 tumor marker, TNM staging, and estrogen and
      progesterone receptor expression in benign and malignant breast lesions.
AB  - Serum tumor marker CA15-3 is widely used in follow-up for assessment of breast
      cancer prognosis. The aim of this study was to evaluate levels among healthy
      females and patients, to assess differences with tumor stage and grade, and to
      determine the relationship with estrogen and progesterone receptor expression.
      One hundred and thirty six Jordanian females were enrolled in this study: Forty
      five were healthy females; seventy-two were diagnosed with breast cancer and
      nineteen diagnosed with benign breast lesions. Elevated serum CA15-3 level was
      significantly observed among breast cancer patients (37.95+/-6.65) compared to
      both healthy (14.97+/-0.8) and benign females (12.30+/-1.55), but no significant
      association was detected between serum CA15-3 level and age of cancer onset,
      menarche age, menopause age, parity and BMI. Decreased CA15-3 level was
      significantly associated with hormone therapy and oral contraceptive consumption
      among breast cancer patients. Significantly elevated CA15-3 serum levels were
      found among grade II, III and stage II and III breast cancer females compared to
      normal healthy females. Elevated CA15-3 serum levels were also found among
      ER+/PR+ (54.242+/-7.89) and ER+/PR- (37.08+/-8.22) compared to healthy control
      females.

PMID- 22631662
TI  - Effectiveness of interventions to increase the participation rate of gastric
      cancer screening in the Republic of Korea: a pilot study.
AB  - This study assessed the effectiveness of three intervention strategies to improve
      the participation rate of gastric cancer screening among people who had never
      undergone such screening, and those who had been screened for the disease, but
      not recently. It was conducted in the Ilsandong-gu District of Goyang City,
      Korea. The population for the current study was restricted to male residents,
      aged 40-65 years, who received an invitation letter to undergo gastric cancer
      screening from the National Health Insurance (NHI) Corporation at the beginning
      of 2010. The subjects were divided into two categories according to their
      screening history: never-screened, and ever-screened. A total of 2,065 men were
      eligible: 803 never-screened and 1,262 ever-screened. In each screening category
      they were randomly assigned to one of three intervention groups: 1) tailored
      telephone counseling; 2) tailored postcard reminder after tailored telephone
      counseling;and 3) tailored telephone counseling after tailored postcard reminder.
      At 3 months post-intervention, never- screened men with any intervention were
      more likely to undergo gastric cancer screening (OR=2.75, 95% CI: 1.22-6.18)
      compared to those in the reference group (no intervention). However, there was no
      statistically significant intervention effect in ever-screened men (OR=1.21, 95%
      CI: 0.65-2.27). Examination of the intervention effects by intervention group
      among never-screened men showed that those in the postcard reminder after
      telephone counseling group to be statistically significantly more likely to
      undergo gastric cancer screening (OR=4.49, 95% CI: 1.79-11.29) than the reference
      group (no intervention). Our results highlight that use of tailored postcard
      reminders after tailored telephone counseling is an effective method to increase
      participation in gastric cancer screening among men who had never been screened.

PMID- 22631663
TI  - Presence of tumour-infiltrating FOXP3+ lymphocytes correlates with immature
      tumour angiogenesis in renal cell carcinomas.
AB  - BACKGROUND: FOXP3+ regulatory T cells (Tregs) inhibit effector T cell functions
      and are implicated in tumour progression. However, together with microvessel
      density (MVD) they remain controversial prognostic predictors for renal cell
      carcinoma (RCC), and potential associations have yet to be determined. The
      objective of this study was to determine the prognostic significance of Tregs and
      MVD and their potential relationship in RCCs. DESIGN: Paraffin-embedded tissues
      from 62 RCC patients were analysed using immunohistochemistry to detect FOXP3+
      lymphocytes, and double immunohistochemistry to detect different microvessel
      types in the tumour interior, rim and normal kidney tissue, and their correlation
      with clinicopathological characteristics. Survival analysis was also performed.
      RESULTS: The presence of FOXP3+ cells in the tumour interior or the rim showed no
      correlation with death from RCC and other pathological characteristics. Negative
      correlations were noted between the immature MVD in the tumour interior or the
      rim and tumour size, tumour stage and overall survival; however, there was no
      correlation with the nuclear grade or pathological type. A positive correlation
      between FOXP3+ Tregs and immature MVD (r=0.363, P=0.014) and mature MVD (r=0.383,
      P=0.009) was confirmed in the tumour interior. However, there was no correlation
      between FOXP3+ Tregs and mature MVD (r=0.281, P=0.076) or immature MVD (r=0.064,
      P=0.692) in the tumour rim. CONCLUSIONS: In this study, a positive correlation
      between the presence of FOXP3+ Tregs and immature and mature MVD in RCC was
      confirmed, which suggests a link between suppression of immunity, tumour
      angiogenesis and poor prognosis.

PMID- 22631664
TI  - Expression analysis of MiR-21, MiR-205, and MiR-342 in breast cancer in Iran.
AB  - MicroRNAs (miRNAs) are short non-coding RNA molecules characterized by their
      regulatory roles in cancer and gene expression. We analyzed the expression of miR
      21, miR-205, and miR-342 in 59 patients with breast cancer. Samples were divided
      into three different groups according to their immunohistochemistry (IHC)
      classification: ER-positive and/or PR-positive group (ER+ and/or PR+; group I);
      HER2-positive group (HER2+; group II); and ER/PR/HER2- negative (ER-/PR-/HER2-;
      group III) as the triple negative group. The expression levels of the 3 miRNAs
      were analyzed in the tumor samples and the compared with the normal neighboring
      dissected tumor (NNDT) samples in all three groups. The expression of miR-21 was
      similar in all three groups. In patients positive for P53 by IHC, positive for
      axillary lymph node metastasis and higher tumor stages, it appeared to have
      significantly elevated. However, significant increase was not found among the 18
      fibroadenoma samples. Both miR-205 and miR-342 expressions were significantly
      down regulated in group III. We conclude that miR-21 does not discriminate
      between different breast cancer groups. In contrast, miR-205 and miR-342 may be
      used as potential biomarkers for diagnosis of triple negative breast cancer.

PMID- 22631665
TI  - Knowledge towards HPV infection and HPV vaccines among Syrian mothers.
AB  - Cervical cancer is caused by HPV infection and can be prevented by early
      vaccination. OBJECTIVE: To assess Syrian women's level of knowledge and
      determinants of good knowledge of cervical cancer, HPV infection and its
      vaccines. METHODS: A cross sectional survey was undertaken among mothers with
      daughters in sixth grade classes enrolled in primary schools in Aleppo city,
      Syria. Samples were selected through cluster sampling and data collected using a
      self-administered questionnaire. RESULTS: Less than a third of the mothers had
      heard of HPV infection and vaccines against cervical cancer and levels of
      knowledge were generally low. Good knowledge was associated with high education
      level, higher family monthly income, having few--less than four children,
      positive history of cervical cancer screening, and working or having relatives
      working in the medical field. The main source of information was television and
      few reported health care providers as a source of knowledge on HPV infection and
      vaccine. CONCLUSION: Since knowledge of HPV infection and its connection with
      cervical cancer and its vaccine are low, more efforts must be made to educate
      Syrians prior to introduction of any HPV vaccination programme. Public health
      efforts must focus on educating mothers, the public as well as health care
      providers.

PMID- 22631666
TI  - Survival and prognostic factors of different sites of head and neck cancer: an
      analysis from Thailand.
AB  - BACKGROUND: Head and neck cancers are prevalent in Thailand, in particular in the
      southern region of the country. However, survival with a large data set has not
      been reported. The purpose of the present study was to evaluate the survival
      figures and the prognostic factors in a cohort of patients treated in a
      university hospital located in the south of Thailand. PATIENTS AND METHODS:
      Consecutive new cases of primary carcinoma of the oral cavity, oropharyx,
      hypopharynx and larynx, treated at Songklanagarind Hospital during 2002 to 2004,
      were analyzed. The 5-year overall survival rates were obtained by the Kaplan
      Meier method. Prognostic factors were identified through multivariate Cox
      regression analysis. RESULTS: A total 1,186 cases were analyzed. Two-thirds
      (66.6%) of the cases were at advanced stage (stage III and IV) at presentation.
      The five-year overall survivals for the whole cohort, oral cavity, oropharynx,
      hypopharynx and larynx were 24.1%, 25.91%, 19.2%, 13.4%, 38.0% respectively.
      Stage and treatment type were strong prognostic factors for all sites. An age
      >=80 years was associated with poor survival in oral cavity and larynx cancer.
      CONCLUSIONS: The results revealed remarkably poor outcomes of the patients in the
      series, indicating a strong need to increase the proportion of early stage
      presentations and maximize the treatment efficacy to improving outcomes. Very old
      patients are of particular concern for treatment care of oral cavity and larynx
      cancer.

PMID- 22631667
TI  - Human papillomavirus infection and prognostic predictors in patients with
      oropharyngeal squamous cell carcinoma.
AB  - This study focused on infection rates and subtypes of human papillomavirus (HPV)
      in patients with oropharyngeal squamous cell carcinoma (OSCC), and the
      relationship between HPV status and prognosis of the disease. We evaluated sixty
      six OSCC patients who met the enrollment criteria during the period from January
      1999 to December 2009. The presence or absence of oncogenic HPV types in tumors
      was determined using the SPF10 LiPA25 assay. Overall survival (OS) and disease
      specific survival (DSS) for HPV positive and HPV negative patients were estimated
      using Kaplan-Meier analysis. The Cox regression model was applied for
      multivariate analysis. HPV-DNA was detected in 11(16.7%) of all specimens. Among
      them, 7 were type HPV-16, while other types were HPV-16/11, HPV-35, HPV-58/52,
      and HPV-33/52/54. Patients with HPV positive tumors were more likely to be
      female, non-smokers and non-drinkers (p=0.002, 0.001 and 0.001, respectively).
      After a median follow-up of 24.5 months, patients with HPV positive tumors had
      significantly better overall survival (HR=0.106[95%CI=0.014-0.787], p=0.016,) and
      disease specific survival (HR=0.121[95%CI=0.016-0.906], p=0.030). Patients with
      HPV positive OSCC have significantly better prognosis than patients with HPV
      negative tumors. HPV infection is an independent prognostic factor.

PMID- 22631668
TI  - Assessment of the knowledge and attitude of female students towards cervical
      cancer prevention at an international university in Japan.
AB  - Cervical cancer resulting from prior infection with human papillomavirus (HPV) is
      a significant public health threat against young Japanese women. A national
      immunization plan to vaccinate 13~16 year old female students against HPV
      infection has been started in Japan since 2010, and may reach almost full
      coverage by the end of 2012. Older age females who may already be sexually active
      are not targeted by this plan but should follow safer sex practices as well as
      periodic screening of the cervix cytology to reduce their risk of developing
      cervical cancer. HPV vaccination alone does not offer full protection either,
      because only some HPV types are covered by the vaccines and the long-term
      efficacy of the vaccines has not been determined yet. Therefore, we did a survey
      at an international university in Japan to study the knowledge and attitude of
      female college students towards prevention of cervical cancer, to examine the age
      when they start sexual activity and other related attributes that may influence
      the risk of cervical cancer. We discuss the results of our survey and what they
      imply for the possible impact of an HPV immunization plan on the risk of cervical
      cancer in Japan, and conclude by an emphasis on the need to increase awareness
      among Japanese female adolescents and to enhance the cervical screening rates
      among older females who are already sexually active.

PMID- 22631669
TI  - MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control
      studies.
AB  - OBJECTIVE: Cumulative evidence suggests that MLH1, the key component in the
      mismatch pathway, plays an important role in human cancers. Two potential
      functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in
      cancer risk. The aim of this meta-analysis was to summarize the evidence for
      associations. METHODS: Eligible studies were identified by searching the
      electronic literature PubMed, ScienceDirect and Embase databases for relevant
      reports and bibliographies. Studies were included if of case-control design
      investigating MLH1 polymorphisms (-93G>A and I219V) and cancer risk with
      sufficient raw data for analysis. Odds ratios (OR) and 95% confidence intervals
      (95% CI) were used to evaluate the strength of associations. RESULTS: Our meta
      analysis from 33 published case-control studies showed the variant A allele of 
      93G>A polymorphism to be associated with increased risk in all genetic models (AA
      vs. GG: OR = 1.22, 95% CI: 1.03-1.44), especially among non-Asians (AA vs. GG: OR
      = 1.28, 95% CI: 1.04-1.58). For the I219V polymorphism, however, there was no
      main effect associated with overall cancer risk in any genetic model.
      CONCLUSIONS: The meta-analysis suggested that the MLH1 -93G>A polymorphism may be
      a biomarker of cancer susceptibility. Large sample association studies and
      assessment of gene-to-gene as well as gene-to-environment interactions are
      required to confirm these findings.

PMID- 22631670
TI  - Gefitinib alone or with concomitant whole brain radiotherapy for patients with
      brain metastasis from non-small-cell lung cancer: a retrospective study.
AB  - BACKGROUND: Gefitinib, a tyrosine kinase inhibitor (TKI) of epidermal growth
      factor receptor (EGFR), is used both as a single drug and concurrently with whole
      brain radiotherapy (WBRT) the standard treatment for brain metastases (BM), and
      is reported to be effective in a few small studies of patients with BM from non
      small-cell lung cancer (NSCLC). However, no study has compared the two treatment
      modalities. This retrospective analysis was conducted to compare the efficacy of
      gefitinib alone with gefitinib plus concomitant WBRT in treatment of BM from
      NSCLC. METHODS: We retrospectively reviewed 90 patients with BM from NSCLC who
      received gefitinib alone (250 mg/day, gefitinib group) or with concomitant WBRT
      (40 Gy/20 f/4 w, gefitinib-WBRT group) between September 2005 and September 2009
      at Sun Yat-Sen University Cancer Center. Forty-five patients were in each group.
      RESULTS: The objective response rate of BM was significantly higher in gefitinib
      WBRT group (64.4%) compared with gefitinib group (26.7%, P<0.001). The disease
      control rate of BM was 71.1% in gefitinib- WBRT group and 42.2% in gefitinib
      group (P=0.006). The median time to progression of BM was 10.6 months in
      gefitinib-WBRT group and 6.57 months in gefitinib group (P<0.001). The median
      overall survival (OS) of gefitinib-WBRT and gefitinib alone group was 23.40
      months and 14.83 months, respectively (HR, 0.432, P=0.002). CONCLUSION: Gefitinib
      plus concomitant WBRT had higher response rate of BM and significant improvement
      in OS compared with gefitinib alone in treatment of BM from NSCLC.

PMID- 22631671
TI  - Pro variant of TP53 Arg72Pro contributes to gastric cancer risk in Asians:
      evidence from a meta-analysis.
AB  - BACKGROUND: Previous studies investigating the association between TP53 Arg72Pro
      polymorphism and gastric cancer (GC) risk in Asian population have reported
      controversial results. Thus, a meta-analysis was performed. METHODS: A
      comprehensive literature search was conducted and 17 case-control studies were
      finally included, involving a total of 5,990 GC cases and 6,812 controls.
      Subgroup analyses were performed by the sample size. RESULTS: Meta-analysis of
      all 17 studies showed variant genotypes of TP53 Arg72Pro to be associated with an
      elevated GC risk in three genetic comparison models (OR(Pro vs. Arg)=1.13, 95%CI
      1.03-1.25, P(OR)=0.01; OR(Homozygote comparison model)=1.33, 95%CI 1.07-1.64,
      P(OR)=0.009; OR(Dominant genetic model)=1.13, 95%CI 1.05-1.22, P(OR)=0.002).
      Besides, a more obvious association was observed after the heterogeneity was
      decreased (all P values less than 0.001). This association was further identified
      by both subgroup and sensitivity analyses. CONCLUSIONS: This meta-analysis
      suggests the Pro variant of TP53 Arg72Pro contributes to gastric cancer risk in
      Asians.

PMID- 22631672
TI  - Early efficacy of Endostar combined with chemoradiotherapy for advanced cervical
      cancers.
AB  - The aim of this study was to investigate the early outcome of Endostar combined
      with chemoradiotherapy for advanced cervical cancer. Fifty-two cases (FIGO IIb to
      IVa) were divided randomly into two groups, receiving chemoradiotherapy alone
      (CRT group) and Endostar combined with chemoradiotherapy (CRT+E group). For the
      patients in the CRT+E group, Endostar was administered daily with the dosage of
      7.5 mg/m2, and cisplatin was administered weekly with the dosage of 20 mg/m2
      during the radiation. The regimens lasted for 4 weeks with no difference in
      chemoradiotherapy between the two groups. The early outcome complete remission
      rate was 73.1%, partial remission rate was 23.1% and the total response rate was
      96.2% in CRT+E group, a significnat improvement on the 34.6%, 42.3% and 76.9%,
      respectively, in the CRT group. One year survive rates were 100% and 84.6% in the
      CRT+E group and CRT groups, the difference being significant. Endostar combined
      with chemoradiotherapy can improve the early outcome of the advanced cervical
      cancer, and adverse effects were not encountered.

PMID- 22631673
TI  - Artificial neural network for prediction of distant metastasis in colorectal
      cancer.
AB  - BACKGROUND AND OBJECTIVES: Artificial neural networks (ANNs) are flexible and
      nonlinear models which can be used by clinical oncologists in medical research as
      decision making tools. This study aimed to predict distant metastasis (DM) of
      colorectal cancer (CRC) patients using an ANN model. METHODS: The data of this
      study were gathered from 1219 registered CRC patients at the Research Center for
      Gastroenterology and Liver Disease of Shahid Beheshti University of Medical
      Sciences, Tehran, Iran (January 2002 and October 2007). For prediction of DM in
      CRC patients, neural network (NN) and logistic regression (LR) models were used.
      Then, the concordance index (C index) and the area under receiver operating
      characteristic curve (AUROC) were used for comparison of neural network and
      logistic regression models. Data analysis was performed with R 2.14.1 software.
      RESULTS: The C indices of ANN and LR models for colon cancer data were calculated
      to be 0.812 and 0.779, respectively. Based on testing dataset, the AUROC for ANN
      and LR models were 0.82 and 0.77, respectively. This means that the accuracy of
      ANN prediction was better than for LR prediction. CONCLUSION: The ANN model is a
      suitable method for predicting DM and in that case is suggested as a good
      classifier that usefulness to treatment goals.

PMID- 22631674
TI  - Knockdown of Cdc25B in renal cell carcinoma is associated with decreased
      malignant features.
AB  - Cdc25 phosphatases are important regulators of the cell cycle. Their abnormal
      expression detected in a number of tumors implies that their dysregulation is
      involved in malignant transformation. However, the role of Cdc25B in renal cell
      carcinomas remains unknown. To shed light on influence on renal cell
      carcinogenesis and subsequent progression, Cdc25B expression was examined by real
      time RT-PCR and western blotting in renal cell carcinoma and normal tissues. 65
      kDa Cdc25B expression was higher in carcinomas than in the adjacent normal
      tissues (P<0.05), positive correlations being noted with clinical stage and
      histopathologic grade (P<0.05). To additionally investigate the role of Cdc25B
      alteration in the development of renal cell carcinoma, Cdc25B siRNA was used to
      knockdown the expression of Cdc25B. Down-regulation resulted in slower growth,
      more G2/M cells, weaker capacity for migration and invasion, and induction of
      apoptosis in 769-P transfectants. Reduction of 14-3-3 protein expression appeared
      related to Cdc25B knockdown. These findings suggest an important role of Cdc25B
      in renal cell carcinoma development and provide a rationale for investigation of
      Cdc2B-based gene therapy.

PMID- 22631675
TI  - Patterns of metastasis and survival in breast cancer patients: a preliminary
      study in an Iranian population.
AB  - Due to lack of sufficient data on characteristics of breast cancer patients and
      risk factors for developing metastasis in Iran this study was designed to
      understand clinical aspects impacting on survival. A cross-sectional study on
      breast cancer patients was conducted in an oncology clinic of the university
      hospital between 1995 and 2010. Data were retrieved from medical records and
      included age, menopausal status, tumor diameter, number of involved nodes,
      histopathological type, estrogen and progesterone receptor expression, c-erbB-2,
      primary and secondary metastasis sites, overall survival, disease free interval
      and type of chemotherapy protocol. The results were analyzed with SPSS 13
      software.The mean age of the patients was 49.2 (27-89) years. The primary tumors
      were mainly ER positive (48%) and PR negative (49.3%). The status of lymph nodes
      dissected and examined in these patients was unknown in 19 patients (25.3%) while
      18 patients (24%) had positive lymph nodes with no report on the number of
      involved nodes. All of the patients had received antracyclin based chemotherapy
      in an adjuvant or metastatic setting. Adjuvant hormonal therapy was administered
      to receptor positive patients. In average, overall survival after recurrence was
      30 months (95%CI 24.605-35.325) for non-skeletal versus 42 months (95%CI 31.211
      52.789) for skeletal metastasis (P= 0.002). The median survival was also greater
      for receptor positive patients; 39 months (95%CI 33.716-44.284) for PR+ versus 26
      months (95%CI 19.210-32.790) for PR- (P=0.047) and 38 months (95%CI 32.908
      43.092) for ER+ versus 27 months (95%CI 18.780-35.220) for ER- patients
      (P=0.016). No relation was found between site of first metastasis and hormone
      receptor, age, tumor diameter, DFI and menopausal status. Sites of metastasis
      were independent of age, size of the tumor, menopausal and hormone receptor
      status in this study. Overall survival provided significant relations with
      respect to receptor status and bone metastasis.

PMID- 22631676
TI  - Health-related quality of life of breast cancer patients in Iran: pooled analysis
      using generalized estimating equations.
AB  - OBJECTIVE: The aim of current study was to evaluate the changes of health-related
      quality of life (HRQoL) and its clinical, demographic and socioeconomic
      determinants during chemotherapy and 4 months follow-up in women with breast
      cancer using a repeated measures framework. METHODS AND MATERIALS: A double blind
      cohort study was performed in 100 breast cancer patients given fluorouracil,
      doxorubicin and cyclophosphamide (FAC) or docetaxel, doxorubicin,
      cyclophosphamide (TAC) in south of Iran. HRQoL was assessed at baseline, end of
      chemotherapy and four months thereafter using the QLQ-C30 questionnaire from
      European Organization for Research and Treatment of Cancer (EORTC). Generalized
      estimating equations (GEE) was applied for statistical analysis. RESULTS: The
      mean of age at baseline was 48.5+/-10.6. 70% and 14% of patients were married and
      smokers, respectively, and 20% suffered from another disease besides breast
      cancer. The results of GEE showed that after control for baseline scores, the
      HRQoL significantly improved over time. Although, the patients in FAC group had
      higher scores than the TAC group, the differences also diminished over time.
      Smoking, marital status and having child affected some scales of HRQoL. None of
      other variables were significantly related to HRQoL. CONCLUSION: Although
      patients in TAC groups had lower level of HRQoL over 8 months follow up, they
      experienced faster improvement than the FAC group. This implies that in long
      term, improvements in TAC group are higher than FAC. Having children was
      positively correlated with HRQoL. Generally, there were no demographic and socio
      economic differences in HRQoL in these patients between the chemotherapeutic
      regimens.

PMID- 22631677
TI  - Association between the FAS/FASL polymorphisms and gastric cancer risk: a meta
      analysis.
AB  - OBJECTIVE: FAS/FASL gene promoter polymorphisms have been repeatedly associated
      with gastric cancer risk, but findings are inconclusive across studies. To
      address a more precise estimation of the relationship, a meta-analysis was
      performed. METHODS: Data were collected from the Pubmed, Medline and EMBASE
      databases, with the last report up to 1 December, 2011. Crude ORs with 95% CIs
      were used to assess the strength of the association by (1) the additive, (2) the
      codominant, (3) the dominant, and (4) the recessive models. RESULTS: A total of
      seven studies, including six studies on FAS -1377G>A polymorphism, five studies
      on FAS -670A>G polymorphism, and six studies on FASL -844T>C polymorphism, were
      identified in the current meta-analysis. Overall, an association of FAS -1377G>A
      (AA versus GG: OR = 1.313, 95% CI = 1.045-1.650, Ph = 0.347, I2 = 10.8) and FASL 
      844T>C (CC versus TT: OR = 1.352, 95% CI = 1.043-1.752, Ph = 0.461, I2 = 0.0)
      polymorphisms with gastric cancer was found in the codominant model. However, we
      did not detect any association between gastric cancer and the FAS -670A>G
      polymorphism. In the subgroup analysis by ethnicity, similar elevated risks were
      also observed in Asian population for FAS -1377G>A (AA versus GG: OR = 1.309, 95%
      CI = 1.041- 1.646, Ph = 0.240, I2 = 27.3) and FASL -844T>C (CC versus TT: OR =
      1.420, 95% CI = 1.081-1.865, Ph = 0.524, I2 = 0.0) polymorphisms. CONCLUSIONS:
      This meta-analysis indicated that FAS -1377G>A and FASL -844T>C polymorphisms
      might be associated with gastric cancer risk.

PMID- 22631678
TI  - Smokers and marriage: attitude of youth in the United Arab Emirates.
AB  - INTRODUCTION: In order to control the tobacco scourge, an array of measures is
      required. Among them is focusing on adolescent relationships as it has been shown
      that being in a close relationship with a smoker or a non smoker will in the long
      run be a major factor in deciding whether the individual adopts smoking for
      initial non-smokers or ceases the habit for initial smokers. OBJECTIVES: To
      assess the attitude of youth towards other smokers and towards marrying a smoker.
      MATERIALS AND METHODS: A cross-sectional study was carried out among 415 students
      from five universities in the United Arab Emirates (UAE). Self-administered
      structured questionnaires were used for data collection. The Chi square test was
      used to detect significant differences between frequencies. RESULTS: Of the 415
      participants who provided their gender information, 99 (24%) were males and 314
      (76%) were females. Of all the participants, 83.5% were not willing to marry
      smokers, while 16.5% were willing. Of those whose parents smoked (106) 68% did
      not like it when their parents smoked, 13.6% had no opinion, 17.5% did not mind,
      while the other 1% had other thoughts. Of those whose close friends smoked, 43.4%
      did not like it, 16.2% did not have any opinion, 36.9% did not mind while 3.5%
      had other thoughts. CONCLUSION: Most participants, both males and females are not
      willing to marry smokers and prefer to have non-smokers as spouses. Also, smokers
      are seen as less attractive by both genders in contrast to what appears as
      popular beliefs amongst youngsters and what is depicted in tobacco
      advertisements. Tobacco control activities can be undertaken in the community and
      colleges by incorporating students as facilitators.

PMID- 22631679
TI  - Quality of life in Malaysian colorectal cancer patients: a preliminary result.
AB  - OBJECTIVE: Rapidly increasing colorectal cancer (CRC) incidence in Malaysia and
      the introduction of cutting edge new treatments, which prolong survival, mean
      that treatment outcome measures meed to be evaluated, including consideration of
      patient's quality of life (QoL) assessment. There are limited data on QoL in CRC
      patients, especially in Malaysia. Therefore, this study was performed focusing on
      cancer stages and age groups. METHODS: The cross sectional study was conducted
      from June to September 2011 at three public tertiary hospitals with the EORTC QLQ
      C-30 questionnaire in addition to face to face interview and review of medical
      records of 100 respondents. RESULTS: The mean age was 57.3 (SD 11.9) years with
      56.0% are males and 44.0% females, 62% of Malay ethnicity, 30% Chinese, 7% Indian
      and 1% Sikh. Majority were educated up to secondary level (42%) and 90%
      respondents had CRC stages III and IV. Mean global health status (GHS) score was
      79.1 (SD 21.4). Mean scores for functional status (physical, emotional, role,
      cognitive, social) rangeds between 79.5 (SD 26.6) to 92.2 (SD 13.7). Mean symptom
      scores (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia,
      dyspnoea, loss of appetite) ranged between 4.00 (SD 8.58) to 20.7 (SD 30.6).
      Respondents role function significantly deteriorates with increasing stage of the
      disease (p=0.044). Females had worse symptoms of pain (p=0.022), fatigue
      (p=0.031) and dyspnoea (p=0.031). Mean insomnia (p=0.006) and diarrhea (p=0.024)
      demonstrated significant differences between age groups. CONCLUSION: QOL in CRC
      patients in this study was comparable to that in other studies done in developed
      countries. Pain, fatigue and dyspnoea are worse among female CRC patients. Given
      that functions deteriorates with advanced stage of the disease at diagnosis, a
      systematic screening programme to detect cases as early as possible is essential
      nationwide.

PMID- 22631680
TI  - Dietary habits contributing to the cancer prevention among health college
      students in Turkey.
AB  - This descriptive study was made to evaluate the dietary habits contributing to
      cancer prevention of 319 health college students. Data collection form included
      questions about demographic characteristics and 33 statements which evaluate
      dietary habits contributing to cancer prevention. Among the students, 56.1%
      consumed fast food outside the home/dormitory twice a week or more and 47% never
      exercised. Moreover, 63.9% of the students reported that their dietary habits
      changed negatively and 69% stated that their fruit and vegetable consumption
      decreased after starting the health college. The students mostly paid attention
      to preserving food and water consumption while they paid least attention to
      maintaining healthy weight and whole grain consumption. Female students, those
      who paid attention to the amount and calorie of the food they consumed, students
      who did not consume fast food, and students who exercised twice a week or three
      times a week had better dietary habits contributing to cancer prevention
      (p<0.05). According to these results we recommend that interventions which will
      reduce fast food consumption and increase fruit and vegetable consumption and
      exercising in university students should be implemented. For this purpose,
      appropriate conditions for preparing and preserving healthy food should be
      provided as well as increasing the frequency of vegetable containing meals and
      providing fruits and salads in every meal at school cafeterias.

PMID- 22631681
TI  - Predictors of mammography screening among Iranian women attending outpatient
      clinics in Tehran, Iran.
AB  - Mammography utilization is low in Iran compared with other countries. Here a
      cross-sectional survey design was used to investigate psycho-social and
      individual factors associated with mammography among 400 women asymptomatic of
      breast cancer. The study was carried out at the four outpatient clinics of Tehran
      during the period from July through October, 2009. We found that mammography
      screening was related to higher self-efficacy and women's occupation. Future
      tailored interventions on potential psycho-social determinants and specific
      demographic factors are critical in increasing mammography screening rates among
      Iranian women.

PMID- 22631682
TI  - Diagnostic utility of p63 (Ab-1) and (Ab-4) tumor markers in the squamous cell
      carcinomas of head and neck.
AB  - P63 is a gene product required in cell cycle regulation which plays vital roles
      in tumor differentiation. Aims of the present study were to assess the frequency,
      pattern, sensitivity and specificity of two p63 protein clones P63 4A4 and P63
      4A4+Y4A3 in squamous cell carcinomas (SCCs). Thirty cases of head and neck region
      SCC diagnosed on the basis of HandE staining were examined along with 60 cases of
      head and neck region biopsies other than squamous cell carcinoma, negative on
      HandE staining, were taken as control. Immunostaining was performed on slides
      according to the Thermo Scientific UltraVision LP detection System. P63 4A4+Y4A3
      clone is more sensitive 96.6% in comparison to 86% in P63 4A4 with having greater
      NPV of 98.3%. The results signify the importance of P63 4A4+Y4A3 marker over the
      old markers and may be used as a confirmatory marker of squamous cell carcinoma.

PMID- 22631683
TI  - Efficacy of exemestane after nonsteroidal aromatase inhibitor use in metastatic
      breast cancer patients.
AB  - BACKGROUND: Previous studies have suggested a lack of complete cross-resistance
      between steroidal (exemestane) and non-steroidal aromatase inhibitors (nSAI).
      METHODS: Eighty-eight metastatic breast cancer (MBC) patients who received 25 mg
      of exemestane orally once a day at the National Cancer Center, Korea, between
      2003 and 2009, were reviewed retrospectively. All patients had received nSAI for
      metastatic disease prior to exemestane therapy. RESULTS: The median age was 52
      years (range, 33-79), and 13 (14.8%) patients were premenopausal who
      concomitantly received GnRH agonist. Exemestane was given as a second- (80.7%) or
      third-line (19.3%) hormone therapy. The clinical benefit (CB) rate (complete
      response + partial response + stable disease >= 24 weeks) was 30.7%, with a
      median CB duration of 10.0 months (range, 6.3-78.7). The median progression-free
      survival (PFS) was 3.0 months (95% confidence interval [CI], 1.99-4.01) and the
      overall survival (OS) 21.5 months (95% CI, 17.96-25.04), with a median follow-up
      of 50.3 months. Patients who achieved CB had longer OS than those patients who
      did not (29.6 vs 17.9 months; P = 0.002). On univariate analysis of predictive
      factors, patients who had achieved CB from previous nSAI tended to show lower CB
      rate (24.6% vs 44.4%, respectively; P = 0.063) and shorter PFS (2.8 vs 4.8
      months, respectively; p = 0.233) than patients who had not. Achieving CB from
      previous nSAI became independent predictive factor for CBR to exemestane on
      multivariable analysis (Odds ratio = 2.852, P = 0.040). CONCLUSIONS: Exemestane
      after nSAI failure was effective in prolonging CB duration. The drug's efficacy
      seemed to be inferior in patients who had benefit from previous nSAI use.

PMID- 22631684
TI  - Dosimetric verification for primary focal hypermetabolism of nasopharyngeal
      carcinoma patients treated with dynamic intensity-modulated radiation therapy.
AB  - OBJECTIVE: To make sure the feasibility with (18F)FDG PET/CT to guided dynamic
      intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma
      patients, by dosimetric verification before treatment. METHODS: Chose 11 patients
      in III~IVA nasopharyngeal carcinoma treated with functional image-guided IMRT and
      absolute and relative dosimetric verification by Varian 23EX LA, ionization
      chamber, 2DICA of I'mRT Matrixx and IBA detachable phantom. Drawing outline and
      making treatment plan were by different imaging techniques (CT and (18F)FDG
      PET/CT). The dose distributions of the various regional were realized by SMART.
      RESULTS: The absolute mean errors of interest area were 2.39%+/-0.66 using 0.6 cc
      ice chamber. Results using DTA method, the average relative dose measurements
      within our protocol (3%, 3 mm) were 87.64% at 300 MU/min in all filed.
      CONCLUSIONS: Dosimetric verification before IMRT is obligatory and necessary.
      Ionization chamber and 2DICA of I'mRT Matrixx was the effective dosimetric
      verification tool for primary focal hyper metabolism in functional image-guided
      dynamic IMRT for nasopharyngeal carcinoma. Our preliminary evidence indicates
      that functional image-guided dynamic IMRT is feasible.

PMID- 22631685
TI  - 5-Aminoisoquinolinone reduces the expression of vascular endothelial growth
      factor-C via the nuclear factor-kappaB signaling pathway in CT26 cells.
AB  - OBJECTIVE: VEGF-C has recently been identified as a key molecule which is
      involved in tumor lymphangiogenesis. The aim of this research was to investigate
      the role of PARP-1 inhibition in the regulation of VEGF-C expression in CT26
      cells. METHODS: CT26 cells were treated with or without the PARP-1 inhibitor 5
      aminoisoquinolinone (5-AIQ). The expression of PARP-1, NF-kB, and VEGF-C proteins
      in CT26 cells was measured by Western blot analysis and the VEGF-C mRNA level was
      determined by reverse transcription polymerase chain reaction (RT-PCR). CT26
      secreted VEGF-C was detected by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The results of Western blot analysis showed that the expression levels
      of PARP-1, NF-kB, and VEGF-C were reduced in 5-AIQ treated CT26 cells and the
      levels of VEGF-C mRNA in 5-AIQ treated CT26 were significantly lower than t in 5
      AIQ-untreated cells (P<0.05). The concentrations of CT26-secreted VEGF-C were
      also dramatically decreased (P<0.05). CONCLUSION: Here, we provide evidence for
      the first time that PARP-1 inhibition dramatically reduces VEGF-C expression via
      the nuclear factor NF-kB signaling pathway. We therefore propose that PARP-1
      inhibition has an anti-lymphangiogenic effect and may contribute to the
      prevention of metastatic dissemination via the lymphatic system.

PMID- 22631686
TI  - Study on soy isoflavone consumption and risk of breast cancer and survival.
AB  - AIM: Isoflavones in soy foods are part of a larger class of flayonoid compounds
      that have have been demonstrated to be potent dietary anti-cancer agents, and the
      effect of soy intake on the survival of ovarian cancer is conflicting. Therefore,
      we aimed to explore the whether soy intake is related to the risk of death of
      breast cancer. METHODS: A prospective study was conducted. A total of 256
      patients included in this study had breast cancer and were recruited between
      January 2004 and January 2006. All of them were followed up from since January
      2011. A univariate Cox's regression analysis was used to assess the association
      between soy intake and survival. RESULTS: The education level, menopausal status,
      ER/PR status and TNM stage were significant difference in the survival of breast
      cancer. The highest soy isoflavone was associated with a decreased death risk of
      breast cancer (OR=0.25, 95% CI=0.09-0.54). Moreover, the higher consumption of
      soy protein also presented a trend decreased breast cancer risk, and the highest
      consumption significantly reduced the cancer risk compared with the lowest
      consumption (OR=0.38, 95% CI=0.17-0.86). CONCLUSION: The present study suggests
      soy intake is associated with a significant reduced death risk of breast cancer
      in Chinese population. Further large sample studies are warranted to confirm the
      inverse association of soy consumption and breast cancer survival by menopausal
      status.

PMID- 22631687
TI  - Prostate cancer epidemiology in a rural area of North Western Greece.
AB  - Epirus is a rural area of North-Western Greece. We reviewed data from 4 hospitals
      for 4.975 patients who underwent prostate biopsy in Epirus in the twelve year
      period from 1999 to 2010. Two six-year periods were compared (1999-2004 and 2004
      2010). All cases of prostate cancer confirmed by biopsy were recorded and age
      standardized incidence rates per 100,000 males were calculated. We also recorded
      the clinical stage for patients diagnosed in our hospital and correlated this
      with PSA and Gleason scores. Percentage of positive prostate biopsies was also
      calculated. There were a total of 1714 new cases during 1999-2010 and the mean
      annual age-adjusted incidence was 34/100,000. The mean incidences during 1999
      2004 and 2005-2010 were 26/100,000 and 42/100,000, respectively. The mean age at
      diagnosis was 74. The most common Gleason score was 6 and the prevalent clinical
      stage was T2. Median PSA at diagnosis was 10.8 ng/ml. There was a significant
      difference between stage cT4 and all other stages regarding PSA value (p=0.000).
      A positive correlation was found between Gleason score and PSA (p=0.013). These
      results are in accordance with the incidence rise recorded in neighboring
      countries of South-East Europe. However we should keep in mind the risk of
      overdiagnosis and the detection of low-risk cancers that would not have caused
      morbidity or death during a man's lifetime anyway.

PMID- 22631688
TI  - Suppression of thalamocortical oscillations following traumatic brain injury in
      rats.
AB  - OBJECT: Traumatic brain injury (TBI) often causes an encephalopathic state,
      corresponding amplitude suppression, and disorganization of
      electroencephalographic activity. Clinical recovery in patients who have suffered
      TBI varies, and identification of patients with a poor likelihood of functional
      recovery is not always straightforward. The authors sought to investigate
      temporal patterns of electrophysiological recovery of neuronal networks in an
      animal model of TBI. Because thalamocortical circuit function is a critical
      determinant of arousal state, as well as electroencephalography organization,
      these studies were performed using a thalamocortical brain slice preparation.
      METHODS: Adult rats received a moderate parietal fluid-percussion injury and were
      allowed to survive for 1 hour, 2 days, 7 days, or 15 days prior to in vitro
      electrophysiological recording. Thalamocortical brain slices, 450-MUm thick, were
      prepared using a cutting angle that preserved reciprocal connections between the
      somatosensory cortex and the ventrobasal thalamic complex. RESULTS: Extracellular
      recordings in the cortex of uninjured control brain slices revealed spontaneous
      slow cortical oscillations (SCOs) that are blocked by (2R)-amino-5
      phosphonovaleric acid (50 MUM) and augmented in low [Mg2+]o. These oscillations
      have been shown to involve simultaneous bursts of activity in both the cortex and
      thalamus and are used here as a metric of thalamocortical circuit integrity. They
      were absent in 84% of slices recorded at 1 hour postinjury, and activity slowly
      recovered to approximate control levels by Day 15. The authors next used
      electrically evoked SCO-like potentials to determine neuronal excitability and
      found that the maximum depression occurred slightly later, on Day 2 following
      TBI, with only 28% of slices showing evoked activity. In addition, stimulus
      intensities needed to create evoked SCO activity were elevated at 1 hour, 2 days,
      and 7 days following TBI, and eventually returned to control levels by Day 15.
      The SCO frequency remained low throughout the 15 days following TBI (40% of
      control by Day 15). CONCLUSIONS: The suppression of cortical oscillatory activity
      following TBI observed in the rat model suggests an injury-induced functional
      disruption of thalamocortical networks that gradually recovers to baseline at
      approximately 15 days postinjury. The authors speculate that understanding the
      processes underlying disrupted thalamocortical circuit function may provide
      important insights into the biological basis of altered consciousness following
      severe head injury. Moreover, understanding the physiological basis for this
      process may allow us to develop new therapies to enhance the rate and extent of
      neurological recovery following TBI.

PMID- 22631689
TI  - Stereotactic radiosurgery for arteriovenous malformations after embolization: a
      case-control study.
AB  - OBJECT: In this paper the authors' goal was to define the long-term benefits and
      risks of stereotactic radiosurgery (SRS) for patients with arteriovenous
      malformations (AVMs) who underwent prior embolization. METHODS: Between 1987 and
      2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs;
      120 patients underwent embolization followed by SRS. In this series, 64 patients
      (53%) had at least one prior hemorrhage. The median number of embolizations
      varied from 1 to 5. The median target volume was 6.6 cm(3) (range 0.2-26.3
      cm(3)). The median margin dose was 18 Gy (range 13.5-25 Gy). RESULTS: After
      embolization, 25 patients (21%) developed symptomatic neurological deficits. The
      overall rates of total obliteration documented by either angiography or MRI were
      35%, 53%, 55%, and 59% at 3, 4, 5, and 10 years, respectively. Factors associated
      with a higher rate of AVM obliteration were smaller target volume, smaller
      maximum diameter, higher margin dose, timing of embolization during the most
      recent 10-year period (1997-2006), and lower Pollock-Flickinger score. Nine
      patients (8%) had a hemorrhage during the latency period, and 7 patients died of
      hemorrhage. The actuarial rates of AVM hemorrhage after SRS were 0.8%, 3.5%,
      5.4%, 7.7%, and 7.7% at 1, 2, 3, 5, and 10 years, respectively. The overall
      annual hemorrhage rate was 2.7%. Factors associated with a higher risk of
      hemorrhage after SRS were a larger target volume and a larger number of prior
      hemorrhages. Permanent neurological deficits due to adverse radiation effects
      (AREs) developed in 3 patients (2.5%) after SRS, and 1 patient had delayed cyst
      formation 210 months after SRS. No patient died of AREs. A larger 12-Gy volume
      was associated with higher risk of symptomatic AREs. Using a case-control matched
      approach, the authors found that patients who underwent embolization prior to SRS
      had a lower rate of total obliteration (p = 0.028) than patients who had not
      undergone embolization. CONCLUSIONS: In this 20-year experience, the authors
      found that prior embolization reduced the rate of total obliteration after SRS,
      and that the risks of hemorrhage during the latency period were not affected by
      prior embolization. For patients who underwent embolization to volumes smaller
      than 8 cm(3), success was significantly improved. A margin dose of 18 Gy or more
      also improved success. In the future, the role of embolization after SRS should
      be explored.

PMID- 22631690
TI  - Radiosurgery after embolization.

PMID- 22631691
TI  - Outcome after severe brain trauma due to acute subdural hematoma.
AB  - OBJECT: In this paper, the authors' goal was to identify factors contributing to
      outcomes after severe traumatic brain injury (TBI) due to acute subdural hematoma
      (SDH). METHODS: Between February 2002 and April 2010, 17 Austrian centers
      prospectively enrolled 863 patients with moderate and severe TBI into
      observational studies. Data regarding accident, treatment, and outcomes were
      collected. Data sets from patients who had severe TBI (Glasgow Coma Scale score <
      9) and acute SDH were selected. Six-month outcomes were classified as "favorable"
      if the Glasgow Outcome Scale (GOS) scores were 5 or 4, and they were classified
      as "unfavorable" if GOS scores were 3 or less. The Rotterdam score was used to
      classify CT findings, and the scores published by Hukkelhoven et al. were used to
      estimate the predicted rates of death and of unfavorable outcomes. Univariate
      (Fisher exact test, t-test, chi-square test) and multivariate (logistic
      regression) statistics were used to identify factors associated with hospital
      mortality and favorable outcome. RESULTS: Of the 738 patients with severe TBI,
      360 (49%) had acute SDH. Of these, 168 (46.7%) died in the hospital, 67 (18.6%)
      survived with unfavorable outcome, and 116 (32.2%) survived with favorable
      outcome. Long-term outcome was unknown in 9 survivors (2.5%). Mortality rates
      predicted by the Rotterdam CT score showed good correlation with observed
      mortality rates. According to the Hukkelhoven scores, observed/predicted ratios
      for mortality and unfavorable outcome were 1.09 and 1.02, respectively.
      CONCLUSIONS: Age, severity of TBI, and neurological status were the main factors
      influencing outcomes after severe TBI due to acute SDH. Nonoperative management
      was associated with significantly higher mortality.

PMID- 22631692
TI  - Ten brain metastases.

PMID- 22631693
TI  - Brain surgery in patients with liver cirrhosis.
AB  - OBJECT: Liver cirrhosis was identified as an independent predictor of poor
      outcomes in patients suffering trauma and in those undergoing major surgeries.
      The aim of this study was to report the authors' experiences treating patients
      with cirrhosis who undergo brain surgeries. METHODS: Between 2004 and 2009, 121
      consecutive patients with cirrhosis underwent 144 brain procedures. Patients were
      categorized as Child-Turcotte-Pugh (referred to as "Child") Class A, B, or C. The
      patient profiles, including the severity of cirrhosis, reason for surgery,
      complications, and prognosis factors, were analyzed. RESULTS: In this
      retrospective study, the overall surgical complication rate for patients with
      cirrhosis was 52.1% and the mortality rate was 24.3%. For patients with acute
      traumatic brain injury (TBI), the complication, rebleeding, and mortality rates
      reached 84.4%, 68.8%, and 37.5%, respectively. Surgery for TBI was a significant
      risk factor for postoperative complications (p = 0.0002) and postoperative
      hemorrhage (p < 0.0001). Otherwise, according to the Child classification, the
      complication rate increased in a stepwise fashion from 38.7% to 60% to 84.2%, the
      rebleeding rate from 29.3% to 48.0% to 63.2%, and the mortality rate from 5.3% to
      38% to 63.2% for Child A, B, and C, respectively. The Child classification was
      associated with higher risk of complications-Child B vs A OR 2.84 (95% CI 1.28
      6.29), Child C vs A OR 5.39 (95% CI 1.32-22.02). It was also associated with risk
      of death-Child C vs A OR 30.43 (95% CI 7.71-120.02), Child B vs A OR 10.88 (95%
      CI 3.42-34.63). CONCLUSIONS: Liver cirrhosis is a poor comorbidity factor for
      brain surgery. The authors' results suggest that the Child classification used
      independently is a poor prognostic factor; in addition, grave outcomes were
      observed in patients with TBI.

PMID- 22631694
TI  - Stereotactic radiosurgery using the Leksell Gamma Knife Perfexion unit in the
      management of patients with 10 or more brain metastases.
AB  - OBJECT: To better establish the role of stereotactic radiosurgery (SRS) in
      treating patients with 10 or more intracranial metastases, the authors assessed
      clinical outcomes and identified prognostic factors associated with survival and
      tumor control in patients who underwent radiosurgery using the Leksell Gamma
      Knife Perfexion (LGK PFX) unit. METHODS: The authors retrospectively reviewed
      data in all patients who had undergone LGK PFX surgery to treat 10 or more brain
      metastases in a single session at the University of Pittsburgh. Posttreatment
      imaging studies were used to assess tumor response, and patient records were
      reviewed for clinical follow-up data. All data were collected by a neurosurgeon
      who had not participated in patient care. RESULTS: Sixty-one patients with 10 or
      more brain metastases underwent SRS for the treatment of 806 tumors (mean 13.2
      lesions). Seven patients (11.5%) had no previous therapy. Stereotactic
      radiosurgery was the sole prior treatment modality in 8 patients (13.1%), 22
      (36.1%) underwent whole-brain radiation therapy (WBRT) only, and 16 (26.2%) had
      prior SRS and WBRT. The total treated tumor volume ranged from 0.14 to 40.21
      cm(3), and the median radiation dose to the tumor margin was 16 Gy. The median
      survival following SRS for 10 or more brain metastases was 4 months, with
      improved survival in patients with fewer than 14 brain metastases, a
      nonmelanomatous primary tumor, controlled systemic disease, a better Karnofsky
      Performance Scale score, and a lower recursive partitioning analysis (RPA) class.
      Prior cerebral treatment did not influence survival. The median survival for a
      patient with fewer than 14 brain metastases, a nonmelanomatous primary tumor, and
      controlled systemic disease was 21.0 months. Sustained local tumor control was
      achieved in 81% of patients. Prior WBRT predicted the development of new adverse
      radiation effects. CONCLUSIONS: Stereotactic radiosurgery safely and effectively
      treats intracranial disease with a high rate of local control in patients with 10
      or more brain metastases. In patients with fewer metastases, a nonmelanomatous
      primary lesion, controlled systemic disease, and a low RPA class, SRS may be most
      valuable. In selected patients, it can be considered as first-line treatment.

PMID- 22631695
TI  - Superficial temporal artery-middle cerebral artery bypass using local anesthesia
      and a sedative without endotracheal general anesthesia.
AB  - OBJECT: Superficial temporal artery (STA)-middle cerebral artery (MCA) bypasses
      have continually evolved, and new strategies have been advocated for reducing
      anesthetic or surgical morbidity and mortality. Further simplifying, and
      decreasing the invasiveness of, STA-MCA bypass by performing this operation
      without endotracheal general anesthesia was believed to be feasible in certain
      subsets of patients. METHODS: The authors performed STA-MCA bypass using local
      anesthesia with a sedative in 10 patients with hemodynamically compromised
      occlusive cerebrovascular disease, as well as multiple comorbidities, between
      February 2010 and September 2011. The technique is based on the preoperative
      identification of the point at which the donor and recipient vessels are in
      closest proximity. Preoperative use of CT angiography allowed the authors to
      identify the target point precisely and use a minimally invasive procedure. All
      patients received dexmedetomidine as the sole sedative agent, together with scalp
      blocking local anesthesia, with an unsecured airway. RESULTS: Successful STA-MCA
      bypass surgeries were achieved via a preselected minimally invasive approach in
      all cases. There was good hemodynamic stability throughout surgery. No airway or
      ventilation complications occurred, and no patients were converted to general
      anesthesia. Subjectively, patients tolerated the technique well with a high rate
      of satisfaction. There were no perioperative morbidities or deaths. Postoperative
      MR angiography confirmed a patent bypass in all patients. All patients remained
      symptom free and returned to normal daily life following the operation.
      CONCLUSIONS: This initial experience confirms the feasibility of performing STA
      MCA bypass without endotracheal general anesthesia. This novel technique produced
      a high degree of patient satisfaction.

PMID- 22631696
TI  - Phase II study of dose-modified busulfan by real-time targeting in allogeneic
      hematopoietic stem cell transplantation for myeloid malignancy.
AB  - We aimed to evaluate the efficacy and safety of allogeneic hematopoietic stem
      cell transplantation with targeted oral busulfan (BU) and cyclophosphamide (CY)
      in a phase II study. Busulfan (1.0 mg/kg) was given initially in six doses. Based
      on the estimated concentration at steady state after the first dose of BU,
      subsequent (7th-16th) doses were adjusted to obtain a targeted overall
      concentration at steady state of 700-900 ng/mL. The primary endpoint was 1-year
      overall survival (OS). Fifty patients were registered and 46 (median age, 53
      years; range, 18-62 years) received planned transplant, including 24 with AML, 16
      with myelodysplastic syndrome, and six with CML. Fourteen patients were
      categorized as standard risk. Nineteen patients received transplant from human
      leukocyte antigen-identical siblings, 27 from unrelated donors. The BU dose
      required reduction in 32 patients and escalation in six patients. One-year OS was
      65% (95% confidence interval, 50-77%). Cumulative incidence of hepatic sinusoidal
      obstruction syndrome was 11%. One-year transplant-related mortality was 18%. Both
      OS and transplant-related mortality were favorable in this study, including
      patients of older age and with high risk diseases. Individual dose adjustment
      based on BU pharmacokinetics was feasible and effective in the current phase II
      study. This trial is registered in the University Hospital Medical Information
      Network Clinical Trial Registry System (UMIN-CTR, ID:C000000156).

PMID- 22631857
TI  - Effects of radiation and lifestyle factors on risks of urothelial carcinoma in
      the Life Span Study of atomic bomb survivors.
AB  - Among the Life Span Study (LSS) of Atomic-bomb survivors, recent estimates showed
      that unspecified bladder cancer had high radiation sensitivity with a notably
      high female-to-male excess relative risk (ERR) per radiation dose ratio and were
      the only sites for which the ERR did not decrease with attained age. These
      findings, however, did not consider lifestyle factors, which could potentially
      confound or modify the risk estimates. This study estimated the radiation risks
      of the most prevalent subtype of urinary tract cancer, urothelial carcinoma,
      while accounting for smoking, consumption of fruit, vegetables, alcohol and level
      of education (a surrogate for socioeconomic status). Eligible study subjects
      included 105,402 (males = 42,890) LSS members who were cancer-free in 1958 and
      had estimated radiation doses. Members were censored due to loss of follow-up,
      incident cancer of another type, death, or the end of calendar year 2001. Surveys
      (by mail or clinical interview) gathered lifestyle data periodically for 1963
      1991. There were 63,827 participants in one or more survey. Five hundred seventy
      three incident urothelial carcinoma cases occurred, of which 364 occurred after
      lifestyle information was available. Analyses were performed using Poisson
      regression methods. The excess relative risk per weighted gray unit (the gamma
      component plus 10 times the neutron component, Gy(w)) was 1.00 (95% CI: 0.43
      1.78) but the risks were not dependent upon age at exposure or attained age.
      Lifestyle factors other than smoking were not associated with urothelial
      carcinoma risk. Neither the magnitude of the radiation ERR estimate (1.00
      compared to 0.96), nor the female-to-male (F:M) ERR/Gy(w) ratio (3.2 compared to
      3.4) were greatly changed after accounting for all lifestyle factors. A
      multiplicative model of gender-specific radiation and smoking effects was the
      most revealing though there was no evidence of significant departures from either
      the additive or multiplicative joint effect models. Among the LSS cohort members
      with doses greater than 0.005 Gy(w) (average dose 0.21 Gy(w)), the attributable
      fraction of urothelial carcinoma due to radiation was 7.1% in males and 19.7% in
      females. Among current smokers, the attributable fraction of urothelial carcinoma
      due to smoking was 61% in males and 52% in females. Relative risk estimates of
      smoking risk were approximately two for smokers compared to nonsmokers. After
      adjustment for lifestyle factors, gender-specific radiation risks and the F:M
      ERR/Gy(w), the ratios of excess urothelial carcinoma risk were similar to the
      estimates without adjusting for lifestyle factors. Smoking was the primary factor
      responsible for excess urothelial carcinoma in this cohort. These findings led us
      to conclude that the radiation risk estimates of urothelial carcinoma do not
      appear to be strongly confounded or modified by smoking, consumption of alcohol,
      fruits, or vegetables, or level of education.

PMID- 22631859
TI  - Fibrin clot structure and fibrinolysis in hypothyroid individuals: the effects of
      normalising thyroid hormone levels.

PMID- 22631858
TI  - Quantitative detection of PfHRP2 in saliva of malaria patients in the
      Philippines.
AB  - BACKGROUND: Malaria is a global health priority with a heavy burden of fatality
      and morbidity. Improvements in field diagnostics are needed to support the agenda
      for malaria elimination. Saliva has shown significant potential for use in non
      invasive diagnostics, but the development of off-the-shelf saliva diagnostic kits
      requires best practices for sample preparation and quantitative insight on the
      availability of biomarkers and the dynamics of immunoassay in saliva. This pilot
      study measured the levels of the PfHRP2 in patient saliva to inform the
      development of salivary diagnostic tests for malaria. METHODS: Matched samples of
      blood and saliva were collected between January and May, 2011 from eight patients
      at Palawan Baptist Hospital in Roxas, Palawan, Philippines. Parasite density was
      determined from thick-film blood smears. Concentrations of PfHRP2 in saliva of
      malaria-positive patients were measured using a custom chemiluminescent ELISA in
      microtitre plates. Sixteen negative-control patients were enrolled at UCLA. A
      substantive difference between this protocol and previous related studies was
      that saliva samples were stabilized with protease inhibitors. RESULTS: Of the
      eight patients with microscopically confirmed P. falciparum malaria, seven tested
      positive for PfHRP2 in the blood using rapid diagnostic test kits, and all tested
      positive for PfHRP2 in saliva. All negative-control samples tested negative for
      salivary PfHRP2. On a binary-decision basis, the ELISA agreed with microscopy
      with 100 % sensitivity and 100 % specificity. Salivary levels of PfHRP2 ranged
      from 17 to 1,167 pg/mL in the malaria-positive group. CONCLUSION: Saliva is a
      promising diagnostic fluid for malaria when protein degradation and matrix
      effects are mitigated. Systematic quantitation of other malaria biomarkers in
      saliva would identify those with the best clinical relevance and suitability for
      off-the-shelf diagnostic kits.

PMID- 22631860
TI  - Ectopic intraorbital lacrimal ductal cyst: a case report.
AB  - Lacrimal ductal cysts are uncommon lesions that can occur everywhere in and
      around the eye. Ectopic location is very rare and can be misleading in the
      differential diagnosis of orbital masses. In this article we present the case of
      a 61-year-old-man with a medial intraconal ductal cyst of his right orbit. The
      patient was successfully treated with surgical excision.

PMID- 22631861
TI  - Interventions to increase enrollment in a large multicenter phase 3 trial of
      carotid stenting vs. endarterectomy.
AB  - BACKGROUND: Randomized clinical trials often encounter slow enrollment. Failing
      to meet sample size requirements has scientific, financial, and ethical
      implications. AIMS: We report interventions used to accelerate recruitment in a
      large multicenter clinical trial that was not meeting prespecified enrollment
      commitments. METHODS: The Carotid Revascularization Endarterectomy vs. Stenting
      Trial began randomization in December 2000. To accelerate enrollment, multiple
      recruitment tactics were initiated, which included expanding the number of sites,
      hiring a recruitment director (May 2003), broadening eligibility criteria (April
      2005), branding with a study logo, Web site, and recruitment materials,
      increasing site visits by study leadership, sending e-mails to the site teams
      after every enrollment, distributing electronic newsletters, and implementing
      investigator and coordinator conferences. RESULTS: From December 2000 through May
      2003, 14 sites became active (54 patients randomized), from June 2003 through
      April 2005, 44 sites were added (404 patients randomized), and from May 2005
      through July 2008, 54 sites were added (2044 patients randomized). During these
      time intervals, the number of patients enrolled per site per year was 1.5, 3.6,
      and 5.6. For the single years 2004 to 2008, the mean monthly randomization rates
      per year were 19.7, 38.1, 56.4, 53.0, and 54.7 (annualized), respectively.
      Enrollment was highest after recruitment tactics were implemented: 677 patients
      in 2006, 636 in 2007, and 657 in 2008 (annualized). The prespecified sample size
      of 2502 patients, 47% asymptomatic, was accomplished on July 2008. CONCLUSIONS:
      Aggressive recruitment tactics and investment in a full-time recruitment director
      who can lead implementation may be effective in accelerating recruitment in
      multicenter trials.

PMID- 22631862
TI  - Distinct repeat motifs at the C-terminal region of CagA of Helicobacter pylori
      strains isolated from diseased patients and asymptomatic individuals in West
      Bengal, India.
AB  - BACKGROUND: Infection with Helicobacter pylori strains that express CagA is
      associated with gastritis, peptic ulcer disease, and gastric adenocarcinoma. The
      biological function of CagA depends on tyrosine phosphorylation by a cellular
      kinase. The phosphate acceptor tyrosine moiety is present within the EPIYA motif
      at the C-terminal region of the protein. This region is highly polymorphic due to
      variations in the number of EPIYA motifs and the polymorphism found in spacer
      regions among EPIYA motifs. The aim of this study was to analyze the polymorphism
      at the C-terminal end of CagA and to evaluate its association with the clinical
      status of the host in West Bengal, India. RESULTS: Seventy-seven H. pylori
      strains isolated from patients with various clinical statuses were used to
      characterize the C-ternimal polymorphic region of CagA. Our analysis showed that
      there is no correlation between the previously described CagA types and various
      disease outcomes in Indian context. Further analyses of different CagA structures
      revealed that the repeat units in the spacer sequences within the EPIYA motifs
      are actually more discrete than the previously proposed models of CagA variants.
      CONCLUSION: Our analyses suggest that EPIYA motifs as well as the spacer sequence
      units are present as distinct insertions and deletions, which possibly have
      arisen from extensive recombination events. Moreover, we have identified several
      new CagA types, which could not be typed by the existing systems and therefore,
      we have proposed a new typing system. We hypothesize that a cagA gene encoding
      higher number EPIYA motifs may perhaps have arisen from cagA genes that encode
      lesser EPIYA motifs by acquisition of DNA segments through recombination events.

PMID- 22631863
TI  - Unintended consequences: the story of health care in the United States.

PMID- 22631865
TI  - Rapid repeat pregnancy in adolescents: do immediate postpartum contraceptive
      implants make a difference?
AB  - OBJECTIVE: The purpose of this study was to determine contraceptive continuation
      and repeat pregnancy rates in adolescents who are offered immediate postpartum
      etonogestrel implant (IPI) insertion. STUDY DESIGN: Participants in an adolescent
      prenatal-postnatal program were enrolled in a prospective observational study of
      IPI insertion (IPI group, 171) vs other methods (control group, 225).
      Contraceptive continuation and repeat pregnancies were determined. RESULTS:
      Implant continuation at 6 months was 96.9% (156/161 participants); at 12 months,
      the continuation rate was 86.3% (132/153 participants). At 6 months, 9.9% of the
      control participants were pregnant (21/213); there were no IPI pregnancies. By 12
      months, 18.6% of control participants (38/204) experienced pregnancy vs 2.6% of
      IPI recipients (4/153; relative risk, 5.0; 95% confidence interval [CI], 1.9
      12.7). Repeat pregnancy at 12 months was predicted by not receiving IPI insertion
      (odds ratio, 8.0; 95% CI, 2.8-23.0) and having >1 child (odds ratio, 2.1; 95% CI,
      1.1-4.3; P = .03). CONCLUSION: IPI placement in adolescents has excellent
      continuation 1 year after delivery; rapid repeat pregnancy is significantly
      decreased compared with control participants.

PMID- 22631866
TI  - Referral to telephonic nurse management improves outcomes in women with
      gestational diabetes.
AB  - OBJECTIVE: We sought to determine whether, among women with gestational diabetes
      mellitus, referral to a telephonic nurse management program was associated with
      lower risk of macrosomia and increased postpartum glucose testing. STUDY DESIGN:
      There was medical center-level variation in the percent of patients referred to a
      telephonic nurse management program at 12 Kaiser Permanente medical centers,
      allowing us to examine in a quasi-experimental design the associations between
      referral and outcomes. RESULTS: Compared with women from centers where the annual
      proportion of referral nurse management was <30%, women who delivered from
      centers with an annual referral proportion >70% were less likely to have a
      macrosomic infant and more likely to have postpartum glucose testing (multiple
      adjusted odds ratio, 0.75; 95% confidence interval, 0.57-0.98 and multiple
      adjusted odds ratio, 22.96; 95% confidence interval, 2.56-3.42, respectively).
      CONCLUSION: Receiving care at the centers with higher referral frequency to
      telephonic nurse management for gestational diabetes mellitus was associated with
      decreased risk of macrosomic infant and increased postpartum glucose testing.

PMID- 22631867
TI  - Urinary incontinence, depression and posttraumatic stress disorder in women
      veterans.
AB  - OBJECTIVE: To study associations between urinary incontinence (UI) symptoms,
      depression, and posttraumatic stress disorder in women veterans. STUDY DESIGN:
      This cross-sectional study enrolled women 20 to 52 years of age registered at 2
      midwestern US Veterans Affairs Medical Centers or outlying clinics within 5 years
      preceding study interview. Participants completed a computer-assisted telephone
      interview assessing urogynecologic, medical, and mental health. Multivariable
      analyses studied independent associations between stress and urgency UI and
      depression and posttraumatic stress disorder. RESULTS: Nine hundred sixty-eight
      women mean aged 38.7 +/- 8.7 years were included. Of these, 191 (19.7%) reported
      urgency/mixed UI and 183 (18.9%) stress UI. Posttraumatic stress disorder (odds
      ratio, 1.8; 95% confidence interval, 1.0-3.1) but not depression (odds ratio,
      1.2; 95% confidence interval, 0.73-2.0) was associated with urgency/mixed UI.
      Stress UI was not associated with posttraumatic stress disorder or depression.
      CONCLUSION: In women veterans, urgency/mixed UI was associated with posttraumatic
      stress disorder but not depression.

PMID- 22631868
TI  - Discussion: 'Mycoplasma genitalium in cervicitis and pelvic inflammatory disease'
      by Bjartling et al.

PMID- 22631869
TI  - Selenium-enhanced electron microscopic imaging of different aggregate forms of a
      segment of the amyloid beta peptide in cells.
AB  - The aggregation of misfolded proteins is a common feature underlying a wide range
      of age-related degenerative disorders, including Alzheimer's and Parkinson's
      diseases. A key aspect of understanding the molecular origins of these conditions
      is to define the manner in which specific types of protein aggregates influence
      disease pathogenesis through their interactions with cells. We demonstrate how
      selenium-enhanced electron microscopy (SE-EM), combined with tomographic
      reconstruction methods, can be used to image, here at a resolution of 5-10 nm,
      the interaction with human macrophage cells of amyloid aggregates formed from
      Abeta(25-36), a fragment of the Abeta peptide whose self-assembly is associated
      with Alzheimer's disease. We find that prefibrillar aggregates and mature fibrils
      are distributed into distinct subcellular compartments and undergo varying
      degrees of morphological change over time, observations that shed new light on
      the origins of their differential toxicity and the mechanisms of their clearance.
      In addition, the results show that SE-EM provides a powerful and potentially
      widely applicable means to define the nature and location of protein assemblies
      in situ and to provide detailed and specific information about their partitioning
      and processing.

PMID- 22631870
TI  - Voxel-based morphometry of the visual-related cortex in primary open angle
      glaucoma.
AB  - PURPOSE: To study changes in the morphometric characteristics of the whole brain
      visual-related cortex in various stages of primary open angle glaucoma (POAG) in
      vivo. MATERIALS AND METHODS: Thirty POAG patients (nine early stage cases and 21
      advanced-late stage cases) and 30 gender-, education-, and age-matched healthy
      controls were enrolled in the study. Image data were obtained with a T1 weighted
      three-dimensional magnetization prepared rapid acquisition gradient echo sequence
      (T1WI 3D MP RAGE). Voxel-based morphometry (VBM) analysis was used to assess
      regional differences in gray matter (GM) densities on T1WI 3D MP RAGE scans of
      patients versus controls. RESULTS: Compared with controls, brain regions with GM
      density changes were not found in the early stage of POAG patients but were found
      in the advanced-late stage of POAG patients. These changes with GM density
      reduction were mainly located in the bilateral primary visual cortex (BA17 and
      BA18), bilateral paracentral lobule (BA5), right precentral gyrus (BA6), right
      middle frontal gyrus (BA9), right inferior temporal gyrus (BA20), right angular
      gyrus (BA39), left praecuneus (BA7), left middle temporal gyrus (BA21), and
      superior temporal gyrus (BA22). Conversely, patients showed increased GM density
      in BA39 near the most damaged regions. In addition, in the advanced-late stage of
      POAG, some reduced GM density areas were related to binocular mean defect (MD)
      and disease duration (ranging from r = -0.761 to r = -0.458). CONCLUSIONS: Our
      results suggest that there are different types of pathogenesis at different
      stages of POAG. Atrophy and degeneration of the visual-related cortex existed in
      the dorsal and ventral visual pathways in the advanced-late stage of POAG but
      were not found in the early stage of POAG using VBM. Such GM density changes are
      likely associated with the pathogenesis of POAG.

PMID- 22631871
TI  - Highly enantioselective organocatalytic trifluoromethyl carbinol synthesis--a
      caveat on reaction times and product isolation.
AB  - Aldol reactions with trifluoroacetophenones as acceptors yield chiral alpha-aryl,
      alpha-trifluoromethyl tertiary alcohols, valuable intermediates in organic
      synthesis. Of the various organocatalysts examined, Singh's catalyst [(2S)-N
      [(1S)-1-hydroxydiphenylmethyl-3-methylbutyl]-2-pyrrolidinecarboxamide] was found
      to efficiently promote this organocatalytic transformation in a highly
      enantioselective manner. Detailed reaction monitoring ((19)F-NMR, HPLC) showed
      that, up to full conversion, the catalytic transformation proceeds under kinetic
      control and affords up to 95% ee in a time-independent manner. At longer reaction
      times, the catalyst effects racemization. For the product aldols, even weak acids
      (such as ammonium chloride) or protic solvents, can induce racemization, too.
      Thus, acid-free workup, at carefully chosen reaction time, is crucial for the
      isolation of the aldols in high (and stable) enantiomeric purity. As evidenced by
      (19)F-NMR, X-ray structural analysis, and independent synthesis of a stable
      intramolecular variant, Singh's catalyst reversibly forms a catalytically
      inactive ("parasitic") intermediate, namely a N,O-hemiacetal with
      trifluoroacetophenones. X-ray crystallography also allowed the determination of
      the product aldols' absolute configuration (S).

PMID- 22631872
TI  - Rat astrocytic tumour cells are associated with an anti-inflammatory microglial
      phenotype in an organotypic model.
AB  - AIM: Microglia form a high proportion of cells in glial tumours but their role in
      supporting or inhibiting tumour growth is unclear. Here we describe the
      establishment of an in vitro model to investigate their role in astrocytomas.
      METHODS: Rat hippocampal slices were prepared and, after 7 days to allow
      microglia to become quiescent, rat C6 astrocytic tumour cells were added. Over
      the following 7 days, infiltration and cell death were studied using fluorescent
      C6 tumour cells and confocal microscopy; immunophenotyping of microglia was
      performed using CD68 (phagocytosis), MHCII (antigen-presentation) and Iba1
      (microglial marker regardless of functional state). Cell proliferation was
      assessed using Ki67 and qPCR to detect cytokine expression. Sham and control
      groups were included. RESULTS: Microscopy showed proliferation of C6 tumour cells
      with both infiltration of tumour cells into the hippocampal tissue and of
      microglia among the tumour cells. Confocal experiments confirmed increasing
      tumour cell infiltration into the hippocampal slice with time (P<0.001),
      associated with cell death (sigma=0.313, P=0.022). Ki67 showed increased
      proliferation (P<0.001), of both tumour cells and Iba1+ microglia and increased
      microglial phagocytosis (CD68: P<0.001). Expression of pro-inflammatory cytokines
      IL1, IL6 and TNFalpha were downregulated with expression of the anti-inflammatory
      cytokine TGFbeta1 maintained. CONCLUSION: This model allows study of the
      proliferation and infiltration of astrocytic tumour cells in central nervous
      system tissue and their interaction with microglia. Our data suggest that
      microglial function is altered in the presence of tumour cells, putatively
      facilitating tumour progression. Manipulation of the microglial functional state
      may have therapeutic value for astrocytic tumours.

PMID- 22631873
TI  - Validation of radiocarpal joint contact models based on images from a clinical
      MRI scanner.
AB  - This study was undertaken to assess magnetic resonance imaging (MRI)-based
      radiocarpal surface contact models of functional loading in a clinical MRI
      scanner for future in vivo studies, by comparison with experimental measures from
      three cadaver forearm specimens. Experimental data were acquired using a Tekscan
      sensor during simulated light grasp. Magnetic resonance (MR) images were used to
      obtain model geometry and kinematics (image registration). Peak contact pressures
      (PPs) and average contact pressures (APs), contact forces and contact areas were
      determined in the radiolunate and radioscaphoid joints. Contact area was also
      measured directly from MR images acquired with load and compared with model data.
      Based on the validation criteria (within 25% of experimental data), out of the
      six articulations (three specimens with two articulations each), two met the
      criterion for AP (0%, 14%); one for peak pressure (20%); one for contact force
      (5%); four for contact area with respect to experiment (8%, 13%, 19% and 23%),
      and three contact areas met the criterion with respect to direct measurements
      (14%, 21% and 21%). Absolute differences between model and experimental PPs were
      reasonably low (within 2.5 MPa). Overall, the results indicate that MRI-based
      models generated from 3T clinical MR scanner appear sufficient to obtain
      clinically relevant data.

PMID- 22631874
TI  - Investigation of prevalence and risk factors for Campylobacter in broiler flocks
      at slaughter: results from a UK survey.
AB  - During 2007-2009 a UK-wide, 3-year stratified randomized survey of UK chicken
      broiler flocks was conducted to estimate the prevalence of Campylobacter-infected
      batches of birds at slaughter. Thirty-seven abattoirs, processing 88.3% of the
      total UK slaughter throughput, were recruited at the beginning of the survey. Of
      the 1174 slaughter batches sampled, 79.2% were found to be colonized with
      Campylobacter, the majority of isolates being C. jejuni. Previous partial
      depopulation of the flock [odds ratio (OR) 5.21], slaughter in the summer months
      (categorized as June, July and August; OR 14.27) or autumn months (categorized as
      September, October and November; OR 1.70) increasing bird age (40-41 days, OR
      3.18; 42-45 days, OR 3.56; ?46 days, OR 13.43) and higher recent mortality level
      in the flock (1.00-1.49% mortality, OR 1.57; ?1.49% mortality, OR 2.74) were all
      identified as significant risk factors for Campylobacter colonization of the
      birds at slaughter. Time in transit to the slaughterhouse of more than 2.5 h was
      identified as a protective factor (OR 0.52).

PMID- 22631875
TI  - Matching physicians' treatment recommendations to patients' treatment preferences
      is associated with improvement in treatment satisfaction.
AB  - BACKGROUND: Dissatisfaction with treatment is common among those with psoriasis.
      While incorporating patients' preferences into the process of treatment decision
      making may improve satisfaction, this relationship has not been clearly
      established. OBJECTIVE: To assess the extent to which matching physicians'
      treatment recommendations to patients' treatment preferences is associated with
      improvement in treatment satisfaction in patients with moderate-to-severe
      psoriasis. METHODS: This prospective cohort study design examined change from
      baseline to 3-month follow-up in four subscales of an established measure of
      treatment satisfaction. Separate multivariate regression models investigated the
      association of change in these subscale scores with an index measuring the match
      between physicians' treatment recommendations and patients' treatment preferences
      at the initial study visit. RESULTS: A closer match between physicians'
      recommendations and patients' preferences was associated with greater improvement
      in treatment satisfaction over time in each of the four subscales: effectiveness
      (beta = 0.53, P < 0.001), side-effects (beta = 0.25, P = 0.009), convenience
      (beta = 0.78, P < 0.001) and global satisfaction (beta = 0.49, P < 0.001).
      Adjusted models explained as much as 76% of the variation in change in treatment
      satisfaction subscales over 3 months. CONCLUSIONS: Further efforts to incorporate
      patients' preferences in treatment decision-making appear justified given the
      strength of independent associations between preference matching and improved
      treatment satisfaction and the extent to which our models explained variation in
      this relationship. An approach based on preference matching shows promise for
      increasing satisfaction in the management of other chronic diseases.

PMID- 22631876
TI  - Identification and management of ocular lipid deposition in association with
      hyperlipidaemia in captive moray eels, Gymnothorax funebris Ranzani, Gymnothorax
      moringa (Cuvier) and Muraena retifera Goode and Bean.
AB  - Ocular lipid deposition and its surgical management and possible association with
      systemic hyperlipidaemia in captive moray eels are described. Ophthalmologic
      examinations, haematology and plasma biochemistry analyses were performed on an
      initial population of captive moray eels (n=10): green moray, Gymnothorax
      funebris Ranzani; spotted moray, Gymnothorax morninga (Cuvier) and reticulated
      moray, Muraena retifera Goode and Bean. Recently captured green moray eels
      comprised the control group (n=9). Clinical signs compatible with ocular lipid
      deposition were identified in six of ten captive eels (60%) vs. none of the
      controls. Green moray eels in the initial captive population (n=5) had
      significantly higher total protein, triglyceride, cholesterol and aspartate amino
      transferase values than the control eels. Dietary management was attempted in all
      captive eels, and surgical intervention was performed in three eels, including
      two from a separate population, with improved ocular clarity within 1month post
      operatively. Histopathological evaluation of surgical specimens and two eyes from
      an additional affected eel that died suggested ocular lipid deposition. Eels in
      captivity have an apparent predisposition for hyperlipidaemia and ocular lipid
      deposition. Although limited in this study and complicated by exhibit restraints,
      dietary management was minimally effective, while surgery improved ocular
      clarity.

PMID- 22631878
TI  - Prevalence and risk factors of excess weight in school children in West Greece.
AB  - The present study estimated the prevalence of childhood obesity and identified
      risk factors in 10-13 year old children. A cross-sectional study was conducted,
      including 200 children and their parents, in seven randomly-selected primary
      schools across Patras, Greece. Height, weight, and waist circumference were
      measured, and self-reported information was collected via face-to-face
      interviews. Body mass index was calculated for the children and their parents.
      The effect of risk factors on overweight and obesity was analyzed using
      regression analysis. The prevalence of overweight and obesity was 32% and 10.5%,
      respectively. The odds of being overweight/obese increased in children whose
      parents had a lower educational level and/or higher body mass index. Fewer daily
      meals and more time spent in front of the television and/or on the computer were
      significantly associated with obesity in 10-13 year old children. The prevalence
      of excess weight in primary school children in Patras is of concern, especially
      for boys. Children's nutritional habits, leisure activities, and parental
      characteristics influence their somatometric characteristics. These findings
      highlight the need for future weight loss interventions targeted at this
      population.

PMID- 22631879
TI  - Identification of a novel HLA-A*24:02:55 allele by sequence-based typing.
AB  - HLA-A*24:02:55 differs from A*24:02:01:01 by a single nucleotide substitution at
      position 295, in exon 2.

PMID- 22631877
TI  - An inpatient rehabilitation model of care targeting patients with cognitive
      impairment.
AB  - BACKGROUND: The course and outcomes of hip fracture patients are often
      complicated by the presence of dementia and delirium, referred to as cognitive
      impairment (CI), which limits access to in-patient rehabilitation. In response to
      this concern, members of our team developed and piloted an in-patient
      rehabilitation model of care (Patient-Centred Rehabilitation Model; PCRM)
      targeting patients with hip fracture and CI (PCRM-CI). We are now conducting a 3
      year study comparing an inpatient rehabilitation model of care for community
      dwelling individuals with hip fracture and CI (PCRM-CI) to usual care to
      determine whether it results in improved mobility at the time of discharge from
      inpatient rehabilitation. METHODS/DESIGN: A non-equivalent pre-post design is
      being used to evaluate the PCRM-CI compared to usual care. All community dwelling
      (private home or retirement home) patients following a hip fracture are eligible
      to participate. Recruitment of both cohorts is taking place at two facilities.
      Target accrual is 70 hip fracture patients in the PCRM-CI cohort and 70 patients
      in the usual care cohort. We are also recruiting 70 health care providers (HCPs),
      who are being trained to implement the PCRM-CI, and their unit managers. Patient
      data are collected at baseline, discharge, and 6 months post-discharge from an
      inpatient rehabilitation program. Evaluations include mobility, physical
      function, and living arrangement. Additional outcome variables are being
      collected from medical records and from the patients via their proxies. Data on
      the prevalence and severity of dementia and delirium are being collected. Staff
      data are collected at baseline and one year after implementation of the model to
      determine change in staff knowledge and attitudes toward patients with hip
      fracture and CI. Bi-monthly semi-structured interviews with unit managers have
      been conducted to examine factors and barriers influencing the model
      implementation. Data collection began in 2009 and is expected to be completed in
      2012. The control cohort of 70 patients has been recruited, and 45 patients have
      been accrued to the intervention group to date. DISCUSSION: Evaluation of this
      model of care is timely given the increasing proportion of persons with cognitive
      impairment and hip fractures. TRIAL REGISTRATION: The study is registered at
      http://clinicaltrials.gov, Identifier NCT01566136.

PMID- 22631880
TI  - Opposing effects of diabetes and tetracycline on the degradation of collagen
      membranes in rats.
AB  - BACKGROUND: Increased collagenolytic activity, characteristic of uncontrolled
      diabetes, may compromise collagen membrane (CM) survival. Tetracycline (TCN)
      possesses anticollagenolytic properties and delays CM degradation in healthy
      animals. This study evaluates the degradation of TCN--immersed and -non-immersed
      CMs in rats with diabetes compared to those with normoglycemia. METHODS: Diabetes
      was induced in 15 12-week-old male Wistar rats by injection of 65 mg/kg
      streptozotocin. The control group consisted of 15 rats with normoglycemia. Sixty
      bilayered CM disks were labeled before implantation with aminohexanoyl-biotin-N
      hydroxy-succinimide ester, of which 30 were immersed in 50 mg/mL TCN solution
      (experimental) or phosphate-buffered saline (PBS) (control). In each animal, two
      disks (control and experimental) were implanted in two midsagittal calvarial
      defects in the parietal bone. Similar non-implanted disks served as baseline.
      After 3 weeks, animals were euthanized, and the calvaria and overlying soft
      tissues were processed for demineralized histologic analysis. Horseradish
      peroxidase-conjugated streptavidin was used to detect the biotinylated collagen.
      The area of residual collagen within the membrane disks was measured and analyzed
      with a digital image analysis system. Several slides from each specimen were also
      stained with hematoxylin and eosin. Statistical analysis consisted of paired and
      unpaired t tests. RESULTS: The amount of residual collagen in PBS-immersed disks
      was lower in rats with diabetes compared to rats with normoglycemia (69% of
      baseline versus 93%, respectively, P <0.001). TCN immersion increased the amount
      of residual collagen contents in both diabetic (83% of baseline) and healthy
      (97.5% of baseline) animals (P <0.0001). CONCLUSION: Diabetes increases CM
      degradation, whereas immersion in 50 mg/mL TCN solution before implantation
      presents an opposite effect.

PMID- 22631881
TI  - Association of leptin in periodontitis and acute myocardial infarction.
AB  - BACKGROUND: Serum leptin concentrations are reported to be elevated in patients
      with periodontal diseases and may have a modulating role in cardiovascular
      diseases. Serum leptin concentrations have not been assessed in periodontitis
      associated with acute myocardial infarction (AMI) to date. The purpose of this
      study was to assess the concentration of serum leptin in periodontitis associated
      with AMI. METHODS: A cross-sectional clinical study was conducted comprising a
      sample size of 120 participants divided into four groups (n = 30 each) based on
      their clinical signs: 1) control; 2) AMI; 3) generalized chronic periodontitis
      (GCP); and 4) GCP + AMI. Body mass index (BMI) was calculated and recorded for
      all the subjects based on BMI chart of the World Health Organization. After
      thorough clinical and oral examination, plaque index (PI), gingival index (GI),
      probing depth (PD), and clinical attachment loss (AL) were recorded. In addition,
      2 mL venous blood was collected by venipuncture from all participants to
      determine serum leptin concentration using the enzyme-linked immunosorbent assay
      method. RESULTS: A strong correlation of serum leptin concentration to BMI was
      observed in AMI, GCP, and GCP + AMI groups. Serum leptin levels were
      significantly elevated in AMI, GCP, and GCP + AMI groups compared to the control
      group. Significant associations between serum leptin concentration and PI, GI,
      PD, and AL were also seen in the GCP group. PI, GI, PD, and AL were statistically
      significantly elevated in GCP + AMI and AMI groups. CONCLUSION: Elevated serum
      leptin concentration was associated with increased BMI, GCP, and AMI and may
      serve as a risk marker for these conditions.

PMID- 22631882
TI  - Profiles of dental caries and periodontal disease in individuals with or without
      psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory disease that is manifested on the
      skin. Studies of oral health in psoriasis patients are limited. The aim of this
      study is to assess the experience and risk of caries and periodontal disease in
      individuals with and without psoriasis. METHODS: The material consisted of 89
      individuals with mild-to-moderate chronic plaque psoriasis and 54 without
      psoriasis, recruited at the University Hospital in Gothenburg, Gothenburg,
      Sweden. Psoriatic arthritis (PsoA) was diagnosed in 25 of the individuals with
      psoriasis. All participants answered questionnaires and were subjected to saliva
      sampling and oral radiologic and clinical examinations. Two computer applications
      were used for illustration of oral disease risk profiles. RESULTS: Individuals
      with psoriasis had lower salivary pH, fewer remaining teeth, fewer sites with
      probing depth <=4 mm, and a lower radiographic alveolar bone level than
      individuals without psoriasis (P <0.05). Most of the differences remained
      significant after controlling for confounders. Differences in alveolar bone
      levels were no longer significant, particularly after introducing the confounder
      sex into the regression model. Similar numbers of decayed and filled teeth, sites
      with deep pockets, sites that bled on probing, and risk profiles were observed.
      Individuals with PsoA exhibited a lower stimulated salivary secretion rate than
      those without psoriasis (P <0.05). CONCLUSIONS: There were no differences in
      profiles of caries and periodontal disease experience and risk between
      individuals with and without psoriasis. Fewer remaining teeth were observed in
      individuals with psoriasis. However, the exact reason for tooth loss could not be
      identified. Meanwhile, the reduced salivary pH in individuals with psoriasis and
      salivary secretion in individuals with PsoA may pose some risk for future caries.

PMID- 22631883
TI  - Splinted and unsplinted short implants in mandibles: a retrospective evaluation
      with 5 to 16 years of follow-up.
AB  - BACKGROUND: The aim of this retrospective study is to investigate the medium- to
      long-term prognosis of short implants in partially and totally edentulous
      patients with mandibular bone atrophy. METHODS: The study involved 109 patients
      with 280 implants placed in the mandible. The implants were 7 or 8.5 mm long and
      3.75 or 4 mm in diameter. The implant surfaces were machined (M; n = 176) or
      rough (R; n = 104). Patients were asked to attend a radiographic and clinical
      follow-up, and their previous clinical records and radiographs were assessed.
      Implant-related and prosthetic failures and complications were recorded. RESULTS:
      The mean follow-up was 9 years (range of 5 to 16 years). The survival rate (SSR)
      and success rate (SR) were calculated using life-table analysis for both M and R
      short implants. The M implants had a 16-year SSR of 95.7% and a corresponding SR
      of 93.9%, whereas the 16-year SSR and SR for the R implants were 97.2% and 95.2%,
      respectively. The mean +/- SD bone resorption for all implants was 1.37 +/- 0.5
      mm. For marginal bone loss, there was no statistically significant difference
      between the two implant lengths (P = 0.38) or diameters (P = 0.34) or between the
      M and R implant surfaces (P = 0.47). CONCLUSIONS: Different implant lengths,
      diameters, and surface treatments do not appear to influence the prognosis of the
      implant. Within the limitation that most of the short implants were splinted to
      longer implants, the reduced length of the fixtures did not worsen the long-term
      survival of the implant-supported fixed prostheses.

PMID- 22631884
TI  - Current advancements in Abeta luminescent probes and inhibitors of Abeta
      aggregation.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that severely
      jeopardizes the health of aging populations all over the world. According to the
      amyloid cascade hypothesis, the pathological progression of AD is associated with
      the formation of amyloid plaques in the brain, resulting from the aggregation of
      amyloid-beta (Abeta) peptides. Over the past few years, vast efforts have been
      dedicated to the development of amyloid probes and inhibitors for the diagnosis
      and effective treatment of AD. We review here recent advancements in luminescent
      probes for the detection of Abeta peptide and fibrils, and the current
      development of small molecule inhibitors of Abeta aggregation. We also highlight
      the key features in each specific example, as well as review new ideas and
      strategies that are crucial for researchers in this field.

PMID- 22631885
TI  - In vivo gene transfer in mouse preimplantation embryos after intraoviductal
      injection of plasmid DNA and subsequent in vivo electroporation.
AB  - The aim of this study was to investigate whether direct injection of nonviral DNA
      into the oviductal lumen and subsequent in vivo electroporation leads to in vivo
      gene transfer in mouse preimplantation embryos present within an oviduct, as an
      alternative to the pre-existing pronuclear microinjection-based transgenesis.
      With this technique, effects of expression of the gene of interest (GOI) on mouse
      preimplantation development can be monitored with relative ease. Superovulated 4
      week-old B6C3F1 female mice (hybrids between C57BL/6N and C3H/HeN) were mated
      with adult B6C3F1 male mice. Two days later, females that had been identified as
      pregnant, based on the presence of copulation plugs, were injected with 1 ul of a
      solution containing an enhanced green fluorescent protein (EGFP) expression
      plasmid (0.5 ug) and 0.05% trypan blue. The entire oviduct was then
      electroporated using tweezer-type electrodes with 8 square-wave pulses of 50 V
      each with 50-ms duration. The next day, the 8-cell stage embryos were collected,
      and their number, morphology, and EGFP-derived fluorescence were recorded. Of the
      12 oviducts (6 females used) examined, 3 contained fluorescent 8-cell stage
      embryos (33%, 19/58 tested), but the intensity of fluorescence varied among the
      embryos. In total, 10% (19/192 tested) of the embryos were fluorescent and the
      fluorescence was maintained in these embryos after 1 day of culture. However, the
      fluorescence disappeared in the late gestational stage fetuses, and the
      transgenes could not be detected. Our results indicate that it is possible to
      transfect in vivo preimplantation embryos, although the success rate appears to
      be relatively low and gene expression is transient. This technology may provide a
      new method for manipulating preimplantation embryos in vivo, by using, for
      example, Cre-mediated conditional DNA recombination.

PMID- 22632030
TI  - Orofacial pain and dysfunction in children with juvenile idiopathic arthritis: a
      case-control study.
AB  - OBJECTIVES: Juvenile idiopathic arthritis (JIA) frequently causes
      temporomandibular joint (TMJ) inflammation. The aim of this study was to evaluate
      the presence of orofacial pain and temporomandibular dysfunction in patients with
      JIA and controls. METHODS. Forty-one patients with JIA and 41 age- and sex
      matched healthy controls participated. Subjects were asked about facial pain
      variables and their influence on daily life. A clinical examination was
      performed. Panoramic radiograph and medical data were extracted from the records.
      RESULTS: Thirty-three of the JIA patients reported TMJ or facial pain compared to
      four of the controls (p < 0.001). Nine of the JIA patients, compared to none of
      the controls, reported that their orofacial symptoms influenced daily life
      severely (p < 0.001). Clinical findings were more prevalent in JIA (p < 0.001).
      The assessments of disease activity correlated to palpation pain of jaw muscles
      (p < 0.001) whereas the presence of structural TMJ changes correlated to reduced
      jaw opening (p < 0.001). CONCLUSIONS: TMJ pain was prevalent in patients with JIA
      and influenced daily life severely for nearly a quarter of them. Collaboration
      between medical and dental care is therefore important.

PMID- 22632031
TI  - Induction of DNA strand breaks is critical to predict the cytotoxicity of
      gemtuzumab ozogamicin against leukemic cells.
AB  - Gemtuzumab ozogamicin (GO) consists of the CD33 antibody linked to calicheamicin.
      The binding of GO to the CD33 antigen on leukemic cells results in
      internalization followed by the release of calicheamicin, thereby inducing DNA
      strand breaks. We hypothesized that the induction of DNA strand breaks would be a
      surrogate marker of GO cytotoxcity. Here, two GO-resistant variants (HL/GO-CSA
      [225-fold], HL/GO [200-fold]) were established by serially incubating human
      leukemia HL-60 cells with GO with or without a P-glycoprotein (P-gp) inhibitor,
      cyclosporine A, respectively. The CD33 positivity was reduced in both variants.
      The HL/GO-CSA cells showed an increased multidrug resistance protein-1 (MRP1)
      transcript, and an MRP1 inhibitor partially reversed GO resistance. The HL/GO
      cells had neither P-gp nor MRP1 overexpression. Microarray analysis and Western
      blotting indicated elevated levels of DNA repair-associated proteins in both
      variants. Two other leukemic subclones, showing either P-gp or MRP1
      overexpression, were also GO-resistant. Using single cell gel electrophoresis
      analysis, it was determined that GO-induced DNA strand breaks increased dose
      dependently in HL-60 cells, whereas the number of breaks was reduced in the GO
      resistant cell lines. The induction of DNA strand breaks was correlated with GO
      sensitivity among these cell lines. The CD33 positivity and the expression levels
      of transporters were not proportional to drug sensitivity. Using primary leukemic
      cells, the induction of DNA strand breaks appeared to be associated with GO
      sensitivity. Thus, GO-induced DNA strand breaks as the final output of the
      mechanism of action would be critical to predict GO cytotoxicity.

PMID- 22632032
TI  - Inhibition of tissue factor pathway inhibitor by the aptamer BAX499 improves
      clotting of hemophilic blood and plasma.
AB  - BACKGROUND: Tissue factor pathway inhibitor (TFPI) is the major inhibitor of
      tissue factor-initiated coagulation, making it an interesting and novel
      therapeutic target in hemophilia treatment. The aptamer BAX499 (formerly
      ARC19499) is designed to improve hemostasis by specifically inhibiting TFPI.
      OBJECTIVES: The aim of the study was to examine the concentration-dependent
      augmentation of clotting by BAX499. METHODS: Whole blood clot formation was
      quantified by rotational thromboelastometry and thromboelastography, and thrombin
      generation in platelet-poor plasma was assessed with the calibrated automated
      thrombogram, in samples from patients with congenital hemophilia A (N=55) and B
      (N=11), patients with acquired hemophilia A (N=1), and healthy controls (N=37).
      RESULTS: BAX499 significantly improved clotting of samples from hemophilic
      patients in a concentration-dependent manner, resulting in clotting profiles in
      samples from patients with severe hemophilia that were similar to those of
      healthy controls. CONCLUSION: BAX499 improved ex vivo clotting parameters in
      blood and plasma from patients with hemophilia A and B with different severity of
      disease, and also in a patient with acquired hemophilia. These results further
      support the contention that anti TFPI strategies may be an effective treatment
      for hemophilic patients.

PMID- 22632033
TI  - Artemether-lumefantrine treatment failure despite adequate lumefantrine day 7
      concentration in a traveller with Plasmodium falciparum malaria after returning
      from Tanzania.
AB  - Artemether-lumefantrine is currently first-line therapy of Plasmodium falciparum
      malaria in many countries. This report describes a treatment failure despite
      adequate drug concentrations in a traveller returning from sub-Saharan Africa.
      Genotyping confirmed recrudescence and suggested reduced sensitivity. Potential
      sub-optimal effect of artemether-lumefantrine highlights the need to follow non
      immune individuals the weeks after treatment.

PMID- 22632034
TI  - Kikuchi-Fujimoto disease: a rare case of orbital involvement.
AB  - We describe a rare case of orbital involvement in Kikuchi-Fujimoto disease, a
      rare, benign, self limiting systemic disease, in a young Italian woman. The
      origin of the disease is unknown, so no specific treatment has been defined.
      Histology has an important role in establishing the diagnosis. In presence of an
      eyelid swelling, it is important to rule out infections, lymphoproliferative
      disorders, and connective tissue diseases. Despite the fact that it is rare in
      Europe, the possibility of this disease should be borne in mind.

PMID- 22632035
TI  - Predictors of poststroke driving or riding in Indian stroke patients (POINT
      Study).
AB  - BACKGROUND: There is no information regarding the proportion of stroke patients
      who drive or ride after a stroke from developing countries. AIM: We aimed to
      study the predictors of poststroke driving or riding and its impact on social
      life in Indian patients. METHODS: This study was done in the stroke and neurology
      clinics of Christian Medical College, Ludhiana, from May 1, 2008 to May 31, 2010.
      Patients were recruited if they had completed >=1-year follow-up. Subjects were
      interviewed using a structured questionnaire. Stroke outcome was assessed by
      using the modified Rankin scale. Outcome was classified as good (modified Rankin
      scale <=2) and poor (modified Rankin scale >2). RESULTS: Two hundred and one
      patients were interviewed. Mean age was 58.0 +/- 13.4 years (median 59 years,
      range 17-85 years), 139 (69.2%) were men. The mean duration of follow-up was 37.4
      +/- 29.2 months (range 19-210 months). Out of 201 patients, 132 (65.7%) drove or
      rode before stroke and among them only 54 (40.9%) returned to driving or riding
      after stroke [men 53 (98.1%)]. Among the 78 who did not return to driving or
      riding, 51 (65.4%) had an impact on social life. In the multivariate logistic
      regression analysis, the predictors of inability to drive were lower education
      (odds ratio 0.32, confidence interval 0.12-0.89, P = 0.03), unemployment (odds
      ratio 4.59, confidence interval 1.67-12.6, P = 0.003), and poor outcome (odds
      ratio 3.97, confidence interval 1.06-14.8, P = 0.04). CONCLUSIONS: Only 40.9% of
      the patients returned to driving or riding. Lower education, unemployment, and
      poor recovery were the predictors of inability to drive or ride. Inability to
      drive had a major impact in their social life.

PMID- 22632036
TI  - Effects of indole on drug resistance and virulence of Salmonella enterica serovar
      Typhimurium revealed by genome-wide analyses.
AB  - BACKGROUND: Many Gram-positive and Gram-negative bacteria produce large
      quantities of indole as an intercellular signal in microbial communities. Indole
      demonstrated to affect gene expression in Escherichia coli as an intra-species
      signaling molecule. In contrast to E. coli, Salmonella does not produce indole
      because it does not harbor tnaA, which encodes the enzyme responsible for
      tryptophan metabolism. Our previous study demonstrated that E. coli-conditioned
      medium and indole induce expression of the AcrAB multidrug efflux pump in
      Salmonella enterica serovar Typhimurium for inter-species communication; however,
      the global effect of indole on genes in Salmonella remains unknown. RESULTS: To
      understand the complete picture of genes regulated by indole, we performed DNA
      microarray analysis of genes in the S. enterica serovar Typhimurium strain ATCC
      14028s affected by indole. Predicted Salmonella phenotypes affected by indole
      based on the microarray data were also examined in this study. Indole induced
      expression of genes related to efflux-mediated multidrug resistance, including
      ramA and acrAB, and repressed those related to host cell invasion encoded in the
      Salmonella pathogenicity island 1, and flagella production. Reduction of invasive
      activity and motility of Salmonella by indole was also observed phenotypically.
      CONCLUSION: Our results suggest that indole is an important signaling molecule
      for inter-species communication to control drug resistance and virulence of S.
      enterica.

PMID- 22632037
TI  - Strategies for non-invasive delivery of biologics.
AB  - Macromolecular therapeutics, in particular, many biologics, is the most advancing
      category of drugs over conventional chemical drugs. The potency and specificity
      of the biologics for curing certain disease made them to be a leading compound in
      the pharmaceutical industry. However, due to their intrinsic nature, including
      high molecular weight, hydrophilicity and instability, they are difficult to be
      administered via non-invasive route. This is a major quest especially in
      biologics, as they are frequently used clinically for chronic disorders, which
      requires long-term administration. Therefore, many efforts have been made to
      develop formulation for non-invasive administration, in attempt to improve
      patient compliance and convenience. In this review, strategies for non-invasive
      delivery, in particular, oral, pulmonary and nasal delivery, that are recently
      adopted for delivery of biologics are discussed. Insulin, calcitonin and heparin
      were mainly focused for the discussion as they could represent protein,
      polypeptide and polysaccharide drugs, respectively. Many recent attempts for non
      invasive delivery of biologics are compared to provide an insight of developing
      successful delivery system.

PMID- 22632038
TI  - Antenna-enhanced photocurrent microscopy on single-walled carbon nanotubes at 30
      nm resolution.
AB  - We present the first photocurrent measurements along single carbon nanotube (CNT)
      devices with 30 nm resolution. Our technique is based on tip-enhanced near-field
      optical microscopy, exploiting the plasmonically enhanced absorption controlled
      by an optical nanoantenna. This allows for imaging of the zero-bias photocurrent
      caused by charge separation in local built-in electric fields at the contacts and
      close to charged particles that cannot be resolved using confocal microscopy.
      Simultaneously recorded Raman scattering images reveal the structural properties
      and the defect densities of the CNTs. Antenna-enhanced scanning photocurrent
      microscopy extends the available set of scanning-probe techniques by combining
      high-resolution photovoltaic and optical probing and could become a valuable tool
      for the characterization of nanoelectronic devices.

PMID- 22632039
TI  - Analytical chemistry no longer neglected but gaps remain.

PMID- 22632040
TI  - Analytical techniques for wine analysis: an African perspective; a review.
AB  - Analytical chemistry is playing an ever-increasingly important role in the global
      wine industry. Chemical analysis of wine is essential in ensuring product safety
      and conformity to regulatory laws governing the international market, as well as
      understanding the fundamental aspects of grape and wine production to improve
      manufacturing processes. Within this field, advanced instrumental analysis
      methods have been exploited more extensively in recent years. Important advances
      in instrumental analytical techniques have also found application in the wine
      industry. This review aims to highlight the most important developments in the
      field of instrumental wine and grape analysis in the African context. The focus
      of this overview is specifically on the application of advanced instrumental
      techniques, including spectroscopic and chromatographic methods. Recent
      developments in wine and grape analysis and their application in the African
      context are highlighted, and future trends are discussed in terms of their
      potential contribution to the industry.

PMID- 22632041
TI  - The role of analytical chemistry in Niger Delta petroleum exploration: a review.
AB  - Petroleum and organic matter from which the petroleum is derived are composed of
      organic compounds with some trace elements. These compounds give an insight into
      the origin, thermal maturity and paleoenvironmental history of petroleum, which
      are essential elements in petroleum exploration. The main tool to acquire the
      geochemical data is analytical techniques. Due to progress in the development of
      new analytical techniques, many hitherto petroleum exploration problems have been
      resolved. Analytical chemistry has played a significant role in the development
      of petroleum resources of Niger Delta. Various analytical techniques that have
      aided the success of petroleum exploration in the Niger Delta are discussed. The
      analytical techniques that have helped to understand the petroleum system of the
      basin are also described. Recent and emerging analytical methodologies including
      green analytical methods as applicable to petroleum exploration particularly
      Niger Delta petroleum province are discussed in this paper. Analytical chemistry
      is an invaluable tool in finding the Niger Delta oils.

PMID- 22632042
TI  - Elemental composition and fatty acid profile of the edible fruits of Amatungula
      (Carissa macrocarpa) and impact of soil quality on chemical characteristics.
AB  - The Amatungula fruit, from Carissa macrocarpa, is commonly consumed by the local
      people of KwaZulu-Natal (KZN), South Africa. Levels of elements in the fruit were
      determined to assess if they conform to recommended dietary allowances (RDAs) and
      to assess for potential toxicities. Soils and fruit samples from nine sites in
      eastern KZN were investigated. Concentrations of elements in the fruit were found
      to be in the order of Ca>Mg>Fe>Mn~Cu~Pb>Se>Cr>Ni>Zn. For the elements in focus,
      except for Pb, all of the elements found in the fruit contribute significantly
      towards the RDAs. Lipid profiling was also done to determine the fruits potential
      as a source of essential fatty acids. The fruit was rich in monounsaturated and
      essential fatty acids with the linoleic acid to alpha-linolenic acid ratio
      conforming to the recommended range for cardiac health. Concentrations of
      elements in soil had no significant effect on plant concentrations, but
      competition between elements in soil influenced their availability. Total soil
      concentrations of most metals studied have significantly correlated Pb
      availability, indicating the impact of these metals on Pb availability. The
      Amatungula fruit showed tendency to accumulate Pb, with Pb levels in fruit at all
      sites being toxic to human health. Site location had a major effect on plant
      concentrations however uptake and distribution was primarily dependent on the
      plants inherent controls, as evidenced by the accumulation and exclusion of
      elements, to meet its physiological requirements.

PMID- 22632043
TI  - Determination of potentially toxic heavy metals in traditionally used medicinal
      plants for HIV/AIDS opportunistic infections in Ngamiland District in Northern
      Botswana.
AB  - The determination of four potentially toxic heavy metals, arsenic, chromium, lead
      and nickel in twelve plant species used for the treatment of perceived HIV and
      AIDS-associated opportunistic infections by traditional healers in Ngamiland
      District in Northern Botswana, a metal mining area, was carried out using atomic
      absorption spectrometry. The medicinal plants; Dichrostachys cinerea, Maerua
      angolensis, Mimusops zeyheri, Albizia anthelmintica, Plumbago zeylanica,
      Combretum imberbe, Indigofera flavicans, Clerodendrum ternatum, Solanum
      panduriforme, Capparis tomentosa, Terminalia sericea and Maytenus senegalensis
      contained heavy metals in varying quantities: arsenic 0.19-0.54 MUg g(-1),
      chromium 0.15-1.27 MUg g(-1), lead 0.12-0.23 MUg g(-1) and nickel 0.09-0.21 MUg
      g(-1) of dry weight. Chromium was found to be the most abundant followed by
      arsenic and lead. Nickel was undetectable in nine plant species. M. senegalensis
      contained the largest amounts of arsenic, chromium and lead. All metals
      determined were below the WHO permissive maximum levels. The possible maximum
      weekly intakes of the heavy metals following treatment regimes were insignificant
      compared to the provisional tolerable weekly intake levels recommended by WHO and
      the Joint FAO/WHO Expert Committee on Food Additives. This suggests that heavy
      metal exposure to patients originating from consumption of traditional medicinal
      plant preparations is within non health-compromising limits.

PMID- 22632044
TI  - Cytochrome c biosensor for determination of trace levels of cyanide and arsenic
      compounds.
AB  - An electrochemical method based on a cytochrome c biosensor was developed, for
      the detection of selected arsenic and cyanide compounds. Boron doped diamond
      (BDD) electrode was used as a transducer, onto which cytochrome c was immobilised
      and used for direct determination of Prussian blue, potassium cyanide and arsenic
      trioxide. The sensitivity as calculated from cyclic voltammetry (CV) and square
      wave voltammetry (SWV), for each analyte in phosphate buffer (pH=7) was found to
      be in the range of (1.1-4.5)*10(-8) A MUM(-1) and the detection limits ranged
      from 4.3 to 9.1 MUM. The biosensor is therefore able to measure significantly
      lower than current Environmental Protection Agency (EPA) and World Health
      Organisation (WHO) guidelines, for these types of analytes. The protein binding
      was monitored as a decrease in biosensor peak currents by SWV and as an increase
      in biosensor charge transfer resistance by electrochemical impedance spectroscopy
      (EIS). EIS provided evidence that the electrocatalytic advantage of BDD electrode
      was not lost upon immobilisation of cytochrome c. The interfacial kinetics of the
      biosensor was modelled as equivalent electrical circuit based on electrochemical
      impedance spectroscopy data. UV-vis spectroscopy was used to confirm the binding
      of the protein in solution by monitoring the intensity of the soret bands and the
      Q bands. FTIR was used to characterise the protein in the immobilised state and
      to confirm that the protein was not denatured upon binding to the pre-treated
      bare BDD electrode. SNFTIR of cyt c immobilised at platinum electrode, was used
      to study the effect of oxidation state on the surface bond vibrations. The
      spherical morphology of the immobilised protein, which is typical of native
      cytochrome c, was observed using scanning electron microscopy (SEM) and confirmed
      the immobilisation of the cytochrome c without denaturisation.

PMID- 22632045
TI  - Selective electronalysis of peracetic acid in the presence of a large excess of
      H2O2 at Au(111)-like gold electrode.
AB  - Peracetic acid (PAA) has been selectively electroanalyzed in the presence of a
      large excess of hydrogen peroxide (H(2)O(2)), about 500 fold that of PAA, using
      Au (111)-like gold electrode in acetate buffer solutions of pH 5.4. Au(111)-like
      gold electrode was prepared by a controlled reductive desorption of a previously
      assembled thiol, typically cysteine, monolayer onto the polycrystalline gold
      (poly-Au) electrode. Cysteine molecules were selectively removed from the Au(111)
      facets of the poly-Au electrode, keeping the other two facets (i.e., Au(110) and
      Au(100)) under the protection of the adsorbed cysteine. It has been found that
      Au(111)-like gold electrode positively shifts the reduction peak of PAA, while,
      fortunately, shifts the reduction peak of H(2)O(2) negatively, achieving a large
      potential separation (around 750 mV) between the two reduction peaks as compared
      with that (around 450 mV) obtained at the poly-Au electrode. This large potential
      separation between the two reduction peaks enabled the analysis of PAA in the
      presence of a large excess of H(2)O(2). In addition, the positive shift of the
      reduction peak of PAA gives the present method a high immunity against the
      interference of the dissolved oxygen.

PMID- 22632046
TI  - Thermodynamic evaluation of the stability of the bone-seeking radiopharmaceutical
      [177Lu]Lu(III)-DOTP under simulated blood plasma conditions.
AB  - The stability and in vivo robustness of [(177)Lu]Lu-DOTP as a potential bone
      targeting radiopharmaceutical was determined with the aid of thermodynamic blood
      plasma modeling simulations. Glass electrode potentiometry was employed to
      measure the stability constants of the complexes of Lu(3+) with DOTP. Similarly,
      the complexes of DOTP with a selection of the important physiological metal ions:
      Ca(2+), Mg(2+), and Cu(2+) were determined, representing the typical interactions
      that the ligand would encounter upon administration. This made possible the
      construction of a blood plasma model of DOTP, aiding in establishing the
      potential susceptibility of the radiopharmaceutical. The ligand binds
      predominantly to calcium in vivo, accounting for 59.6% of that initially
      introduced as a component of the Lu-DOTP complex. Furthermore, due to a
      preference of the DOTP to bind to Cu(2+) it causes mobilization of the ions in
      blood plasma, and would therefore indicate a deficiency if the ligand is
      administered at a concentration of 8.5 * 10(-5) mol dm(-3). The lutetium-ions are
      preferentially bound to DOTP, with as much as 98.1% of the Lu(3+) occupying the
      ligand under physiological conditions.

PMID- 22632047
TI  - The use of multi-channel silicone rubber traps as denuders for polycyclic
      aromatic hydrocarbons.
AB  - Atmospheric polycyclic aromatic hydrocarbons are ubiquitous environmental
      pollutants, which may be present both in the gaseous phase and adsorbed onto the
      surface of particles. Denuders are sampling devices which have been effectively
      employed in such partitioning applications. Here we describe and characterise a
      novel miniature denuder consisting of two multi-channel silicone rubber traps
      (each 178 mm long, 6 mm o.d. containing 22 silicone tubes), separated by a quartz
      fibre filter for particle phase collection. The denuder only requires a small
      portable personal sampling pump to provide sampling flow rates of ~0.5 L min(-1).
      Theoretical considerations indicated that the air flow through the denuder was
      expected to be laminar, and the linear velocity arising from longitudinal
      diffusion was found to be negligible. The calculated particle transmission
      efficiency through the denuder was found to be essentially 100% for particles>50
      nm, whilst the experimental overall efficiency, as determined by CPC and SMPS
      measurements, was 92 +/- 4%. The size resolved transmission efficiency was <60%
      for particles below 20 nm and 100% for particles larger than 200 nm. Losses could
      have been due to diffusion and electrostatic effects. Semi-volatile gaseous
      analytes are pre-concentrated in the silicone of the trap and may be thermally
      desorbed using a commercially available desorber, allowing for total transfer and
      detection of the collected analytes by GC-MS. This enhances detection limits and
      allows for lower sampling flow rates and shorter sampling times, which are
      advantageous for studies requiring high temporal resolution.

PMID- 22632048
TI  - Development of a dispersive liquid-liquid microextraction method for the
      determination of fluoroquinolones in chicken liver by high performance liquid
      chromatography.
AB  - A simple and cost effective sample pre-treatment method, dispersive liquid-liquid
      microextraction (DLLME), has been developed for the extraction of six
      fluoroquinolones (FQs) from chicken liver samples. Clean DLLME extracts were
      analyzed for fluoroquinolones using liquid chromatography with diode array
      detection (LC-DAD). Parameters such as type and volume of disperser solvent, type
      and volume of extraction solvent, concentration and composition of phosphoric
      acid in the disperser solvent and pH were optimized. Linearity in the
      concentration range of 30-500 MUg kg(-1) was obtained with regression
      coefficients ranging from 0.9945 to 0.9974. Intra-day repeatability expressed as
      % RSD was between 4 and 7%. The recoveries determined in spiked blank chicken
      livers at three concentration levels (i.e. 50, 100 and 300 MUg kg(-1)) ranged
      from 83 to 102%. LODs were between 5 and 19 MUg kg(-1) while LOQs ranged between
      23 and 62 MUg kg(-1). All of the eight chicken liver samples obtained from the
      local supermarkets were found to contain at least one type of fluoroquinolone
      with enrofloxacin being the most commonly detected. Only one sample had four
      fluoroquinolone antibiotics (ciprofloxacin, difloxacin, enrofloxacin,
      norfloxacin). Norfloxacin which is unlicensed for use in South Africa was also
      detected in three of the eight chicken liver samples analyzed. The concentration
      levels of all FQs antibiotics in eight samples ranged from 8.8 to 35.3 MUg kg(
      1), values which are lower than the South African stipulated maximum residue
      limits (MRL).

PMID- 22632050
TI  - 35Cl/37Cl isotope effects in 103Rh NMR of [RhCl(n)(H2O)(6-n)](3-n) complex anions
      in hydrochloric acid solution as a unique 'NMR finger-print' for unambiguous
      speciation.
AB  - A detailed analysis of the (35)Cl/(37)Cl isotope effects observed in the 19.11
      MHz (103)Rh NMR resonances of [RhCl(n)(H(2)O)(6-n)](3-n) complexes (n=3-6) in
      acidic solution at 292.1K, shows that the 'fine structure' of each (103)Rh
      resonance can be understood in terms of the unique isotopologue and in certain
      instances the isotopomer distribution in each complex. These (35)Cl/(37)Cl
      isotope effects in the (103)Rh NMR resonance of the [Rh(35/37)Cl(6)](3-) species
      manifest only as a result of the statistically expected (35)Cl/(37)Cl
      isotopologues, whereas for the aquated species such as for example
      [Rh(35/37)Cl(5)(H(2)O)](2-), cis-[Rh(35/37)Cl(4)(H(2)O)(2)](-) as well as the mer
      [Rh(35/37)Cl(3)(H(2)O)(3)] complexes, additional fine-structure due to the
      various possible isotopomers within each class of isotopologues, is visible. Of
      interest is the possibility of the direct identification of stereoisomers cis
      [RhCl(4)(H(2)O)(2)](-), trans-[RhCl(4)(H(2)O)(2)](-), fac-[RhCl(3)(H(2)O)(3)] and
      mer-[RhCl(3)(H(2)O)(3)] based on the (103)Rh NMR line shape, other than on the
      basis of their very similar delta((103)Rh) chemical shift. The (103)Rh NMR
      resonance structure thus serves as a novel and unique 'NMR-fingerprint' leading
      to the unambiguous assignment of [RhCl(n)(H(2)O)(6-n)](3-n) complexes (n=3-6),
      without reliance on accurate delta((103)Rh) chemical shifts.

PMID- 22632049
TI  - A study of the removal of heavy metals from aqueous solutions by Moringa oleifera
      seeds and amine-based ligand 1,4-bis[N,N-bis(2-picoyl)amino]butane.
AB  - Uptake for lead, copper, cadmium, nickel and manganese from aqueous solution
      using the Moringa oleifera seeds biomass (MOSB) and amine-based ligand (ABL) was
      investigated. Experiments on two synthetic multi-solute systems revealed that
      MOSB performed well in the biosorption and followed the decreasing orders
      Pb(II)>Cu(II)>Cd(II)>Ni(II)>Mn(II) and Zn(II)>Cu(II)>Ni(II). The general trend of
      the heavy metal ions uptake by the amine-based ligand followed decreased in the
      order Mn>Cd>Cu>Ni>Pb, which is the reverse trend for what was observed for MOSB.
      Comparing the single- and multi-metal solutions, there was no clear effect in the
      biosorption capacity of MOSB suggesting the presence of sufficient active binding
      sites for all metal ions studied. The MOSB performance is also not affected by pH
      in the range 3.5-8.

PMID- 22632051
TI  - Construction and performance characteristics of new ion selective electrodes
      based on carbon nanotubes for determination of meclofenoxate hydrochloride.
AB  - This work offers construction and comparative evaluation the performance
      characteristics of conventional polymer (I), carbon paste (II) and carbon
      nanotubes chemically modified carbon paste ion selective electrodes (III) for
      meclofenoxate hydrochloride are described. These electrodes depend mainly on the
      incorporation of the ion pair of meclofenoxate hydrochloride with phosphomolybdic
      acid (PMA) or phosphotungestic acid (PTA). They showed near Nernestian responses
      over usable concentration range 1.0 * 10(-5) to 1.0 * 10(-2)M with slopes in the
      range 55.15-59.74 mV(concentrationdecade)(-1). These developed electrodes were
      fully characterized in terms of their composition, response time, working
      concentration range, life span, usable pH and temperature range. The electrodes
      showed a very good selectivity for Meclo with respect to a large number of
      inorganic cations, sugars and in the presence of the degradation product of the
      drug (p-chloro phenoxy acetic acid). The standard additions method was applied to
      the determination of MecloCl in pure solution, pharmaceutical preparations and
      biological samples. Dissolution testing was also applied using the proposed
      sensors.

PMID- 22632052
TI  - Novel method for determining DDT in vapour and particulate phases within
      contaminated indoor air in a malaria area of South Africa.
AB  - The organochlorine insecticide DDT (1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane) is still used for malaria vector control in certain areas of
      South Africa. The strict Stockholm Convention on Persistent Organic Pollutants
      (POPs) allows spraying on the inside of traditional dwellings with DDT. In rural
      villages contaminated dust presents an additional pathway for exposure to DDT. We
      present a new method for the determination of DDT in indoor air where separate
      vapour and particulate samples are collected in a single step with a denuder
      configuration of a multi-channel open tubular silicone rubber
      (polydimethylsiloxane (PDMS)) trap combined with a micro quartz fibre filter. The
      multi-channel PDMS trap section of the denuder concentrates vapour phase
      insecticide whereas particle associated insecticide is transferred downstream
      where it is collected on a micro-fibre filter followed by a second multi-channel
      PDMS trap to capture the blow-off from the filter. The multi-channel PDMS trap
      and filter combination are designed to fit a commercial thermal desorber for
      direct introduction of samples into a GC-MS. The technique is solvent-free.
      Analyte extraction and sample clean-up is not required. Two fractions, vapour
      phase and particulate phase p,p'-DDT, o,p'-DDT; p,p'-DDD, o,p'-DDD; p,p'-DDE and
      o,p'-DDE in 4 L contaminated indoor air, were each quantitatively analysed by GC
      MS using isotopically labelled ring substituted (13)C(12) -p,p'-DDT as an
      internal standard. Limits of detection were 0.07-0.35 ng m(-3) for p,p'-DDT, o,p'
      DDT, p,p'-DDD, o,p'-DDD, p,p'-DDE and o,p'-DDE. Ratios of airborne p,p'-DDD/p,p'
      DDT and of o,p'-DDT/p,p'-DDT are unusual and do not match the ideal certified
      ingredient composition required of commercial DDT. Results suggest that the DDT
      products used for indoor residual spraying (IRS) prior to, and during 2007, may
      have been compromised with regards to insecticidal efficacy, demonstrating the
      power of this new environmental forensics tool.

PMID- 22632053
TI  - Two multidimensional chromatographic methods for enantiomeric analysis of o,p'
      DDT and o,p'-DDD in contaminated soil and air in a malaria area of South Africa.
AB  - In rural parts of South Africa the organochlorine insecticide DDT (1,1,1
      trichloro-2,2-bis(p-chlorophenyl)ethane) is still used for malaria vector control
      where traditional dwellings are sprayed on the inside with small quantities of
      technical DDT. Since o,p'-DDT may show enantioselective oestrogenicity and
      biodegradability, it is important to analyse enantiomers of o,p'-DDT and its
      chiral degradation product, o,p'-DDD, for both health and environmental-forensic
      considerations. Generally, chiral analysis is performed using heart-cut
      multidimensional gas chromatography (MDGC) and, more recently, comprehensive two
      dimensional gas chromatography (GC*GC). We developed an off-line gas
      chromatographic fraction collection (heart-cut) procedure for the selective
      capturing of the appropriate isomers from a first apolar column, followed by
      reinjection and separation on a second chiral column. Only the o,p'-isomers of
      DDT and DDD fractions from the first dimension complex chromatogram (achiral
      apolar GC column separation) were selectively collected onto a
      polydimethylsiloxane (PDMS) multichannel open tubular silicone rubber trap by
      simply placing the latter device on the flame tip of an inactivated flame
      ionisation detector (FID). The multichannel trap containing the o,p'-heart-cuts
      was then thermally desorbed into a GC with time-of-flight mass spectrometry
      detection (GC-TOFMS) for second dimension enantioselective separation on a chiral
      column (beta-cyclodextrin-based). By selectively capturing only the o,p'-isomers
      from the complex sample chromatogram, (1)D separation of ultra-trace level
      enantiomers could be achieved on the second chiral column without matrix
      interference. Here, we present solventless concentration techniques for
      extraction of DDT from contaminated soil and air, and report enantiomeric
      fraction (EF) values of o,p'-DDT and o,p'-DDD obtained by a new multidimensional
      approach for heart-cut gas chromatographic fraction collection for off-line
      second dimension enantiomeric separation by (1)D GC-TOFMS of selected isomers.
      This multidimensional method is compared to the complementary technique of
      comprehensive GC*GC-TOFMS using the same enantioselective column, this time as
      the first dimension of separation.

PMID- 22632054
TI  - Correlation of diabetic retinopathy and corneal neuropathy using confocal
      microscopy.
AB  - PURPOSE/AIM: To employ corneal confocal microscopy to assess differences in the
      extent of corneal nerve fiber alterations between diabetic patients classed
      according to retinopathy status and nondiabetic patients. MATERIALS AND METHODS:
      Two hundred seventy-eight corneas of 139 patients with type 2 diabetes mellitus
      and 94 corneas of 47 age-matched control participants were scanned using corneal
      confocal microscopy. Images of the subbasal nerve plexus were collected and
      analyzed for nerve fiber density (NFD), nerve branch density (NBD), nerve fiber
      length (NFL), and nerve fiber tortuosity (NFT). Diabetic patients were
      categorized into three groups according to the classification of diabetic
      retinopathy (DR) proposed in the Early Treatment of Diabetic Retinopathy Study,
      based on indirect fundoscopy, fundus photography, and fluorescein angiography
      findings. A separate classification into four groups according to the severity of
      peripheral diabetic neuropathy (DN) was also used, based on the results of
      clinical and electrodiagnostic examinations. RESULTS: Average NFD, NBD, and NFL
      differed significantly according to DR status and were found to be lower, whereas
      NFT was found to be higher in diabetic patients than control participants. A
      positive correlation between diabetic corneal neuropathy and peripheral DN was
      also found. CONCLUSIONS: Nerve fiber alterations of the subbasal nerve plexus of
      diabetic corneas appear to progress in parallel with DR and peripheral DN.
      Corneal confocal microscopy could possibly represent a promising adjuvant
      technique for the early diagnosis and assessment of human DN.

PMID- 22632055
TI  - Enhancing chemosensitivity in ABCB1- and ABCG2-overexpressing cells and cancer
      stem-like cells by an Aurora kinase inhibitor CCT129202.
AB  - Imidazopyridine CCT129202 is an inhibitor of Aurora kinase activity and displays
      a favorable antineoplastic effect in preclinical studies. Here, we investigated
      the enhanced effect of CCT129202 on the cytotoxicity of chemotherapeutic drugs in
      multidrug resistant (MDR) cells with overexpression of ATP-binding cassette (ABC)
      transporters and cancer stem-like cells. CCT129202 of more than 90% cell survival
      concentration significantly enhanced the cytotoxicity of substrate drugs and
      increased the intracellular accumulations of doxorubicin and rhodamine 123 in
      ABCB1 and ABCG2 overexpressing cells, while no effect was found on parental
      sensitive cells. Interestingly, CCT129202 also potentiated the sensitivity of
      cancer stem-like cells to doxorubicin. Importantly, CCT129202 increased the
      inhibitory effect of vincristine and paclitaxel on ABCB1 overexpressing KBv200
      cell xenografts in nude mice and human esophageal cancer tissue overexpressing
      ABCB1 ex vivo, respectively. Furthermore, the ATPase activity of ABCB1 was
      inhibited by CCT129202. Homology modeling predicted the binding conformation of
      CCT129202 within the large hydrophobic cavity of ABCB1. On the other hand,
      CCT129202 neither apparently altered the expression levels of ABCB1 and ABCG2 nor
      inhibited the activity of Aurora kinases in MDR cells under the concentration of
      reversal MDR. In conclusion, CCT129202 significantly reversed ABCB1- and ABCG2
      mediated MDR in vitro, in vivo and ex vivo by inhibiting the function of their
      transporters and enhanced the eradication of cancer stem-like cells by
      chemotherapeutic agents. CCT129202 may be a candidate as MDR reversal agent for
      antineoplastic combination therapy and merits further clinical investigation. 

PMID- 22632056
TI  - Malignant anomalous left coronary artery associated with acute coronary syndrome
      and subsequent post-operative secondary stenosis of the reimplanted anomalous
      left coronary artery.
AB  - We present a case of a 14-year-old boy who presented with symptoms resulting from
      an anomalous left coronary artery. He underwent corrective surgery to reimplant
      the left coronary artery into the left coronary sinus. After 3 months, he
      developed new symptoms. On further investigation, a tight ostial stenosis of the
      left coronary artery was observed and the patient underwent left internal mammary
      artery to left anterior descending coronary artery bypass graft. This case
      showcases the importance of multi-modality imaging in the diagnosis of coronary
      artery anomalies and potential post-surgical complications.

PMID- 22632057
TI  - Terbinafine in the treatment of dermatophyte toenail onychomycosis: a meta
      analysis of efficacy for continuous and intermittent regimens.
AB  - OBJECTIVE: To compare mycological and complete cures of terbinafine continuous
      and intermittent regimens in the treatment of toenail onychomycosis. METHODS: The
      PubMed database was searched using the terms "terbinafine", "onychomycosis",
      "continuous" and "pulse(d)" or "intermittent". The inclusion criteria were head
      to-head comparison of terbinafine pulse and continuous regimens for dermatophyte
      toenail infections. Risk ratios were calculated for intention-to-treat and
      evaluable patient analyses, when possible. Pooled estimates for total and
      subgroup analyses were calculated using a random effect model, Mantel-Haenszel
      method and their probabilities were calculated with z-statistics. RESULTS: Nine
      studies from eight publications were included. Two continuous regimens and four
      intermittent regimens were investigated. A pooled risk ratio of 0.87 was obtained
      for intention-to-treat (95% CI: 0.79-0.96, P = 0.004, n = 6) and evaluable
      patient (95% CI: 0.80-0.96, P = 0.003, n = 8) analyses of mycological cure,
      favouring continuous terbinafine. For complete cure, pooled risk ratios of 0.97
      (95% CI: 0.77-1.23, P = 0.82, n = 7) for intention-to-treat and 0.93 (95% CI:
      0.76-1.13, P = 0.44, n = 9) for evaluable patient analyses showed equality of the
      two regimens. The pulse regimen that demonstrated consistently comparable results
      to the continuous terbinafine regimen was two pulses of terbinafine 250 mg/day
      for 4 weeks on/4 weeks off. CONCLUSIONS: Meta-analysis of published studies of
      toenail onychomycosis showed that a continuous terbinafine regimen is generally
      significantly superior to a pulsed terbinafine regimen for mycological cure. In
      contrast, some pulse terbinafine regimens were as effective as continuous
      terbinafine regimens for complete cure.

PMID- 22632058
TI  - A new overtraining protocol for mice based on downhill running sessions.
AB  - 1. The purpose of the present study was to verify whether a downhill running
      protocol was able to induce non-functional overreaching in > 75% of mice. 2. Mice
      were divided into control (C), trained (TR) and overtrained (OTR) groups.
      Bodyweight and food intake were recorded weekly. The incremental load test (ILT)
      and the exhaustive test (ET) were used to measure performance before and after
      aerobic training and overtraining protocols. 3. Although the bodyweight of the
      OTR group was lower than that of the C group at the end of Week 7, the food
      intake of the OTR group was higher than that of the C and TR groups at the end of
      Week 8. Evaluation of results from the ILT and ET revealed significant intra- and
      inter-group differences: whereas the parameters measured by both tests increased
      significantly in the TR group, they were significantly decreased in the OTR
      group. 4. In conclusion, this new overtraining protocol based on downhill running
      sessions induced non-functional overreaching in 100% of mice.

PMID- 22632059
TI  - Placentophagia in humans and nonhuman mammals: causes and consequences.
AB  - Afterbirth ingestion by nonhuman mammalian mothers has a number of benefits: (1)
      increasing the interaction between the mother and infant; (2) potentiating
      pregnancy-mediated analgesia in the delivering mother; (3) potentiating maternal
      brain opioid circuits that facilitate the onset of caretaking behavior; and (4)
      suppressing postpartum pseudopregnancy. Childbirth is fraught with additional
      problems for which there are no practical nonhuman animal models: postpartum
      depression, failure to bond, hostility toward infants. Ingested afterbirth may
      contain components that ameliorate these problems, but the issue has not been
      tested empirically. The results of such studies, if positive, will be medically
      relevant. If negative, speculations and recommendations will persist, as it is
      not possible to prove the negative. A more challenging anthropological question
      is "why don't humans engage in placentophagia as a biological imperative?" Is it
      possible that there is more adaptive advantage in not doing so?

PMID- 22632060
TI  - The conspicuous absence of placenta consumption in human postpartum females: the
      fire hypothesis.
AB  - The absence of human placentophagy, the maternal consumption of the afterbirth,
      is puzzling given its ubiquity and probable adaptive value in other mammals. We
      propose that human fire use may have led to placentophagy avoidance in our
      species. In our environment of evolutionary adaptedness, gravid women would
      likely have been regularly exposed to smoke and ash, which is known to contain
      harmful substances. Because the placenta filters some toxicants which then
      accumulate there across pregnancy, maternal placentophagy may have had
      deleterious consequences for the overall fitness of mother, offspring, or both,
      leading to its elimination from our species' behavioral repertoire.

PMID- 22632062
TI  - Dietary goal attainment measures and psychosocial factors among Mexican Americans
      and non-Hispanic whites with type 2 diabetes.
AB  - Diabetes education programs need improved measures of goal setting for dietary
      control of diabetes. Additionally, measures of patient experiences with dietary
      goal setting are needed to better prepare patients for diabetes self-management.
      Measures of dietary goals and strategies were investigated via survey of 100
      Mexican Americans and non-Hispanic whites with type 2 diabetes at a community
      clinic. Analyses tested novel goal measures as stages of change and goal
      attainment with a food plan compared to a traditional measure of food plan
      adherence. Ethnic groups varied in some reported experiences with goal setting
      education and goal attainment, but did not differ in most clinical
      characteristics of diabetes. Results indicated that different measures of goal
      setting vary in their psychosocial predictors, suggesting changes in how health
      care providers use and monitor goal setting for patients.   At the time this
      research was conducted, Dr. Briggs Early was a doctoral candidate in the
      Department of Food Science and Human Nutrition at Washington State University.
      She is currently an Assistant Professor of Biochemistry and Nutrition at Pacific
      Northwest University of Health Sciences - College of Osteopathic Medicine, and a
      certified diabetes educator, and insulin pump trainer in Yakima, Washington.

PMID- 22632061
TI  - Determination of nutritional and energy value of Viburnum mullaha Buch.-Ham. Ex
      D. Don (Indian cranberry).
AB  - Nutritional and energy value of an underutilized wild edible Viburnum mullaha was
      determined. Vitamin analysis confirmed that the fruit contains high amounts of
      vitamin C (122.27 mg/100 g), vitamin B2 (0.14 mg/g), and vitamin E (13.47 mg/g).
      Macronutrient profile revealed that Viburnum mullaha is a rich source of
      carbohydrates (18.4 g/100 g), proteins (11.3 g/100 g), and lipids (18.4 g/100 g).
      It was calculated that 100 g of fruit berries can provide an average of 284.4
      kcal (1185.7 kJ) energy. Analysis of magnesium, copper, iron, zinc, and manganese
      estimated by atomic absorption spectrophotometer confirmed that fruit berries of
      Viburnum mullaha can be utilized for developing various edible products. This is
      the first study ever on the biochemical analysis and nutritional value of this
      species; hence, it will provide nutritional statistics that scientific societies
      and the pharmaceutical and nutraceutical industries can use for their expanding
      investigations of the ultrasonically assisted technique described here in food
      and medicine.

PMID- 22632063
TI  - Eating maps: places, times, and people in eating episodes.
AB  - This project developed a method for constructing eating maps that portray places,
      times, and people in an individual's eating episodes. Researchers used seven
      consecutive days of qualitative eating recall interviews from 42 purposively
      sampled U.S. adults to draw a composite eating map of eating sites, meals, and
      partners for each person on a template showing home, work, automobile, other
      homes, and other places. Participants evaluated their own maps and provided
      feedback. The eating maps revealed diverse places, times, and partners. Eating
      maps offer a flexible tool for eliciting, displaying, validating, and applying
      information to visualize eating patterns within contexts.

PMID- 22632064
TI  - Pharmacokinetics of dexamethasone following intra-articular, intravenous,
      intramuscular, and oral administration in horses and its effects on endogenous
      hydrocortisone.
AB  - This study investigated and compared the pharmacokinetics of intra-articular (IA)
      administration of dexamethasone sodium phosphate (DSP) into three equine joints,
      femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the
      intramuscular (IM), oral (PO) and intravenous (IV) administrations. No
      significant differences in the pharmacokinetic estimates between the three joints
      were observed with the exception of maximum concentration (Cmax ) and time to
      maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were
      16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9 (24.0-72.1) ng/mL, respectively. The
      Tmax for IAC, IAF, and IAS were 1.0 (0.75-4.0), 0.62 (0.5-1.0), and 0.25 (0.08
      0.25) h, respectively. Median (range) elimination half-lives for IA and IM
      administrations were 3.6 (3.0-4.6) h and 3.4 (2.9-3.7) h, respectively. A 3
      compartment model was fitted to the plasma dexamethasone concentration-time curve
      following the IV administration of DSP; alpha, beta, and gamma half-lives were
      0.03 (0.01-0.05), 1.8 (0.34-2.3), and 5.1 (3.3-5.6) h, respectively. Following
      the PO administration, the median absorption and elimination half-lives were 0.34
      (0.29-1.6) and 3.4 (3.1-4.7) h, respectively. Endogenous hydrocortisone plasma
      concentrations declined from a baseline of 103.8 +/- 29.1-3.1 +/- 1.3 ng/mL at
      20.0 +/- 2.7 h following the administration of DSP and recovered to baseline
      values between 96 and 120 h for IV, IA, and IM administrations and at 72 h for
      the PO.

PMID- 22632065
TI  - Quality of life in colorectal cancer patients with diarrhoea after surgery: a
      longitudinal study.
AB  - AIMS AND OBJECTIVES: The purposes of this study were to examine how quality of
      life in colorectal cancer patients with diarrhoea changes with time after surgery
      and to identify variables influencing patients' quality of life three months
      following surgery. BACKGROUNDS: Colorectal cancer is one of the most common
      cancers in the world. Literature that focuses on the impact of the basic
      attributes, disease characteristics and diarrhoea distress on the quality of life
      in diarrhoea patients is quite rare. DESIGN: Survey. METHODS: A longitudinal
      study design was employed with a three-month tracking period. Data were collected
      in structured, one-on-one interviews at one week and one, two and three months
      after surgery. Variance and effects of quality of life were analysed by repeated
      measures analysis of variance and generalised estimating equation. RESULTS:
      Results showed that colorectal cancer patients (n = 35) with diarrhoea after
      surgery will over time be gradually satisfied with their overall quality of life.
      Physical health satisfaction is lowest at 1 week after surgery, and it will over
      time gradually increase. Satisfaction with mental health has the lowest score and
      does not improve with time. Satisfaction with social relationships is highest
      between one week and two months after surgery. Satisfaction of environmental
      relationship will improve with time after surgery. The study results also
      indicate that patients with lower quality of life satisfaction are younger,
      women, have had R hemicolectomy and experience higher diarrhoea distress.
      CONCLUSIONS: Colorectal cancer patients with diarrhoea after surgery will become
      more satisfied with their overall quality of life with time. Physical and
      environmental satisfaction will all improve with time. Younger patients will be
      more dissatisfied with their social and environmental health. More severe
      diarrhoea distress will impact patients' quality of life the most. RELEVANCE TO
      CLINICAL PRACTICE: These results can serve as reference for clinical care
      providers to patients with colorectal cancer after surgery.

PMID- 22632067
TI  - Characterization of the novel HLA-DPB1*139:01 allele identified by sequence-based
      typing in a Chinese Han individual.
AB  - Compared with HLA-DPB1*24:01, DPB1*139:01 has two changes at nucleotide positions
      280 (A to C) and 338 (G to T).

PMID- 22632068
TI  - Unusual isotope effect in the reaction of chlorosilylene with trimethylsilane-1
      d. Absolute rate studies and quantum chemical and Rice-Ramsperger-Kassel-Marcus
      calculations provide strong evidence for the involvement of an intermediate
      complex.
AB  - Time-resolved studies of chlorosilylene, ClSiH, generated by the 193 nm laser
      flash photolysis of 1-chloro-1-silacyclopent-3-ene, have been carried out to
      obtain rate constants for its bimolecular reaction with trimethylsilane-1-d,
      Me(3)SiD, in the gas phase. The reaction was studied at total pressures up to 100
      Torr (with and without added SF(6)) over the temperature range of 295-407 K. The
      rate constants were found to be pressure independent and gave the following
      Arrhenius equation: log[(k/(cm(3) molecule(-1) s(-1))] = (-13.22 +/- 0.15) +
      [(13.20 +/- 1.00) kJ mol(-1)]/(RT ln 10). When compared with previously published
      kinetic data for the reaction of ClSiH with Me(3)SiH, kinetic isotope effects,
      k(D)/k(H), in the range from 7.4 (297 K) to 6.4 (407 K) were obtained. These far
      exceed values of 0.4-0.5 estimated for a single-step insertion process. Quantum
      chemical calculations (G3MP2B3 level) confirm not only the involvement of an
      intermediate complex, but also the existence of a low-energy internal
      isomerization pathway which can scramble the D and H atom labels. By means of
      Rice-Ramsperger-Kassel-Marcus modeling and a necessary (but small) refinement of
      the energy surface, we have shown that this mechanism can reproduce closely the
      experimental isotope effects. These findings provide the first experimental
      evidence for the isomerization pathway and thereby offer the most concrete
      evidence to date for the existence of intermediate complexes in the insertion
      reactions of silylenes.

PMID- 22632069
TI  - Reliability and validity of the continence self-efficacy scale in Turkish women
      with urinary incontinence.
AB  - This study investigated the psychometric properties of the Continence Self
      Efficacy Scale. Data was collected from 128 women who had urinary incontinence
      using the following instruments: the Continence Self-Efficacy Scale, the Broome
      Pelvic Muscle Exercise Self-Efficacy Scale, the International Consultation on
      Incontinence Questionnaire Short Form, and the Beck Depression Inventory. The
      validity of the Continence Self-Efficacy Scale was investigated using
      confirmatory factor analysis and convergent and divergent validity analyses. The
      reliability of the Continence Self-Efficacy Scale was examined in terms of
      internal consistency and test-retest correlations. Confirmatory factor analysis
      indicated a three -factor model that had acceptable goodness-of-fit indices. The
      convergent validity of the Continence Self-Efficacy Scale was supported by a
      positive correlation between the Continence Self-Efficacy Scale and the Broome
      Pelvic Muscle Exercise Self-Efficacy Scale. The divergent validity of the
      Continence Self-Efficacy Scale was supported by negative relationships between
      the Continence Self-Efficacy Scale and the Beck Depression Inventory. The
      Cronbach's alpha values regarding internal consistency were 0.94 for the overall
      scale and 0.92-0.93 for the subscales. Test-retest correlations were 0.75 for the
      overall scale and 0.52-0.74 for the subscales. The Continence Self-Efficacy Scale
      is a valid and reliable instrument for use in Turkish women with urinary
      incontinence.

PMID- 22632066
TI  - Altered small-world properties of gray matter networks in breast cancer.
AB  - BACKGROUND: Breast cancer survivors, particularly those treated with
      chemotherapy, are at significantly increased risk for long-term cognitive and
      neurobiologic impairments. These deficits tend to involve skills that are
      subserved by distributed brain networks. Additionally, neuroimaging studies have
      shown a diffuse pattern of brain structure changes in chemotherapy-treated breast
      cancer survivors that might impact large-scale brain networks. METHODS: We
      therefore applied graph theoretical analysis to compare the gray matter
      structural networks of female breast cancer survivors with a history of
      chemotherapy treatment and healthy age and education matched female controls.
      RESULTS: Results revealed reduced clustering coefficient and small-world index in
      the brain network of the breast cancer patients across a range of network
      densities. In addition, the network of the breast cancer group had less highly
      interactive nodes and reduced degree/centrality in the frontotemporal regions
      compared to controls, which may help explain the common impairments of memory and
      executive functioning among these patients. CONCLUSIONS: These results suggest
      that breast cancer and chemotherapy may decrease regional connectivity as well as
      global network organization and integration, reducing efficiency of the network.
      To our knowledge, this is the first report of altered large-scale brain networks
      associated with breast cancer and chemotherapy.

PMID- 22632070
TI  - Phase behavior of elastin-like synthetic recombinamers in deep eutectic solvents.
AB  - Deep eutectic solvents promoted the stabilization of the collapsed state of
      elastin-like recombinamers  - and the subsequent formation of aggregates  - upon
      the loss of the structural water molecules involved in hydrophobic hydration.
      Cryo-etch scanning electron microscopy allowed the observation of these
      aggregates in neat deep eutectic solvents. The suppression of the lower critical
      solution temperature transition, observed by differential scanning calorimetry
      and dynamic light scattering, confirmed the presence of the elastin-like
      recombinamers in their collapsed state. Actually, the transition from the
      collapsed to the expanded state was suppressed even after moderate aqueous
      dilution  - for water contents ranging from nil to ca. 45 wt %  - and it was only
      recovered upon further addition of water  - above 50 wt %. These features
      revealed the preferred stabilization of the collapsed state in not only neat deep
      eutectic solvents but also partially hydrated deep eutectic solvents. We consider
      that the capability to trigger the lower critical solution temperature transition
      by partial hydration of deep eutectic solvent may open interesting perspectives
      for nano(bio)technological applications of elastin-like recombinamers.

PMID- 22632091
TI  - Enhancement of malignant properties of human osteosarcoma cells with disialyl
      gangliosides GD2/GD3.
AB  - The expression and implications of gangliosides in human osteosarcomas have not
      been systematically analyzed. In this study, we showed that gangliosides GD3 and
      GD2 are highly expressed in the majority of human osteosarcoma cell lines derived
      from oral cavity regions. Introduction of GD3 synthase cDNA into a GD3/GD2
      negative (GD3/GD2-) human osteosarcoma subline resulted in the establishment of
      GD3/GD2+ transfectant cells. They showed increased cell migration and invasion
      activities in wound healing and Boyden chamber invasion assays, respectively,
      compared to the control cells. When treated with serum, GD3/GD2+ cells showed
      stronger tyrosine phosphorylation of p130Cas, focal adhesion kinase, and paxillin
      than GD3/GD2- cells. In particular, paxillin underwent much stronger
      phosphorylation, suggesting its role in cell motility. Furthermore, we tried to
      dissect the roles of GD3 and GD2 in the malignant properties of the transfectant
      cells by establishing single ganglioside-expressing cells, that is, either GD3 or
      GD2. Although GD3/GD2+ cells showed the most malignant properties, GD2+ cells
      showed almost equivalent levels to GD3/GD2+ cells in invasion and migration
      activities, and in the intensities of tyrosine phosphorylation of paxillin. Among
      Src family kinases, Lyn was expressed predominantly, and was involved in the
      invasion and motility of GD3- and/or GD2-expressing transfectants. Furthermore,
      it was elucidated by gene silencing that Lyn was located in a different pathway
      from that of FAK to eventually lead paxillin activation. These results suggested
      that GD2/GD3 are responsible for the enhancement of the malignant features of
      osteosarcomas, and might be candidate targets in molecular-targeted therapy.

PMID- 22632092
TI  - Lentivirus-mediated platelet gene therapy of murine hemophilia A with pre
      existing anti-factor VIII immunity.
AB  - BACKGROUND: The development of inhibitory antibodies, referred to as inhibitors,
      against exogenous factor VIII in a significant subset of patients with hemophilia
      A remains a persistent challenge to the efficacy of protein replacement therapy.
      Our previous studies using the transgenic approach provided proof-of-principle
      that platelet-specific expression could be successful in treating hemophilia A in
      the presence of inhibitory antibodies. OBJECTIVE: To investigate a clinically
      translatable approach for platelet gene therapy of hemophilia A with pre-existing
      inhibitors. METHODS: Platelet FVIII expression in preimmunized FVIII(null) mice
      was introduced by transplantation of lentivirus-transduced bone marrow or
      enriched hematopoietic stem cells. FVIII expression was determined with a
      chromogenic assay. The transgene copy number per cell was quantitated with real
      time PCR. Inhibitor titer was measured with the Bethesda assay. Phenotypic
      correction was assessed by the tail clipping assay and an electrolytically
      induced venous injury model. Integration sites were analyzed with linear
      amplification-mediated PCR. RESULTS: Therapeutic levels of platelet FVIII
      expression were sustained in the long term without evoking an anti-FVIII memory
      response in the transduced preimmunized recipients. The tail clip survival test
      and the electrolytic injury model confirmed that hemostasis was improved in the
      treated animals. Sequential bone marrow transplants showed sustained platelet
      FVIII expression resulting in phenotypic correction in preimmunized secondary and
      tertiary recipients. CONCLUSIONS: Lentivirus-mediated platelet-specific gene
      transfer improves hemostasis in mice with hemophilia A with pre-existing
      inhibitors, indicating that this approach may be a promising strategy for gene
      therapy of hemophilia A even in the high-risk setting of pre-existing inhibitory
      antibodies.

PMID- 22632093
TI  - Discriminant analysis of the autism spectrum disorder observation for children.
AB  - PURPOSE: To run a discriminant analysis on the individual items and the total
      scale of the ASD-OC to determine if they significantly discriminated between ASD
      and atypical groups. METHOD: The measure was administered to 78 children as part
      of an outpatient evaluation. RESULTS: The DA revealed that all of the items,
      excluding five, were significant predictors by themselves. Additionally, Wilks'
      lambda was significant, lambda = 0.16, chi(2)= 115.91, p < 0.001 for the
      function, indicating that all of the items together significantly discriminated
      between groups. The DA was run again excluding those items mentioned above and
      the variability accounted for by all of the items and prediction of group
      membership decreased. Therefore, all 45 items were retained for inclusion in the
      final version of the ASD-OC. CONCLUSION: The ASD-OC is able to discriminate
      between ASD and atypical groups.

PMID- 22632095
TI  - Musculoskeletal ultrasound prompts a rare diagnosis of Mycobacterium marinum
      infection.

PMID- 22632094
TI  - Molecular determinants of selectivity and efficacy at the dopamine D3 receptor.
AB  - The dopamine D3 receptor (D3R) has been implicated in substance abuse and other
      neuropsychiatric disorders. The high sequence homology between the D3R and D2R,
      especially within the orthosteric binding site (OBS) that binds dopamine, has
      made the development of D3R-selective compounds challenging. Here, we deconstruct
      into pharmacophoric elements a series of D3R-selective substituted-4
      phenylpiperazine compounds and use computational simulations and binding and
      activation studies to dissect the structural bases for D3R selectivity and
      efficacy. We find that selectivity arises from divergent interactions within a
      second binding pocket (SBP) separate from the OBS, whereas efficacy depends on
      the binding mode in the OBS. Our findings reveal structural features of the
      receptor that are critical to selectivity and efficacy that can be used to design
      highly D3R-selective ligands with targeted efficacies. These findings are
      generalizable to other GPCRs in which the SBP can be targeted by bitopic or
      allosteric ligands.

PMID- 22632096
TI  - Relationship of seminal plasma antioxidants and serum male hormones with sperm
      chromatin status in male factor infertility.
AB  - We explored the relationship between sperm chromatin integrity, hormone levels,
      seminal plasma total antioxidant capacity (TAC), and routine sperm parameters in
      men with male factor (MF, n = 81) and non-male factor (NMF, n = 52) infertility.
      Semen and blood were collected and examined from men undergoing evaluation for
      infertility in the Avicenna Infertility Clinic. We have examined each patient for
      serum hormones (LH, FSH, E2, DHEA), sperm chromatin damage, level of
      protamination and seminal plasma TAC. Levels of FSH, LH, sperm chromatin damage,
      and abnormal protamination were significantly higher in MF vs. NMF groups (p <
      0.001). Sperm chromatin damage was correlated with percentage of CMA(3)- positive
      sperm (r = 0.64, p < 0.001) and with sperm concentration (r = -0.36, p < 0.001),
      motility (r = -0.21, p < 0.05), and morphologically normal spermatozoa (r = 
      0.29, p < 0.001). Linear regression showed sperm chromatin damage was related to
      percentage of CMA(3)- positive sperm (p < 0.001) in ungrouped patients. It was
      related to both percentage of CMA(3)- positive sperm and serum DHEA in the MF
      group (p < 0.001 and p < 0.05, respectively). Sperm chromatin maturity assessed
      by CMA(3) test was inversely related to sperm chromatin damage assessed by the
      toludine blue assay. Male factor infertility associated with sperm chromatin
      damage may be related to sperm protamination and to serum DHEA.

PMID- 22632097
TI  - Equity in public health standards: a qualitative document analysis of policies
      from two Canadian provinces.
AB  - INTRODUCTION: Promoting health equity is a key goal of many public health
      systems. However, little is known about how equity is conceptualized in such
      systems, particularly as standards of public health practice are established. As
      part of a larger study examining the renewal of public health in two Canadian
      provinces, Ontario and British Columbia (BC), we undertook an analysis of
      relevant public health documents related to equity. The aim of this paper is to
      discuss how equity is considered within documents that outline standards for
      public health. METHODS: A research team consisting of policymakers and academics
      identified key documents related to the public health renewal process in each
      province. The documents were analyzed using constant comparative analysis to
      identify key themes related to the conceptualization and integration of health
      equity as part of public health renewal in Ontario and BC. Documents were coded
      inductively with higher levels of abstraction achieved through multiple readings.
      Sets of questions were developed to guide the analysis throughout the process.
      RESULTS: In both sets of provincial documents health inequities were defined in a
      similar fashion, as the consequence of unfair or unjust structural conditions.
      Reducing health inequities was an explicit goal of the public health renewal
      process. In Ontario, addressing "priority populations" was used as a proxy term
      for health equity and the focus was on existing programs. In BC, the
      incorporation of an equity lens enhanced the identification of health inequities,
      with a particular emphasis on the social determinants of health. In both,
      priority was given to reducing barriers to public health services and to forming
      partnerships with other sectors to reduce health inequities. Limits to the
      accountability of public health to reduce health inequities were identified in
      both provinces. CONCLUSION: This study contributes to understanding how health
      equity is conceptualized and incorporated into standards for local public health.
      As reflected in their policies, both provinces have embraced the importance of
      reducing health inequities. Both concepualized this process as rooted in
      structural injustices and the social determinants of health. Differences in the
      conceptualization of health equity likely reflect contextual influences on the
      public health renewal processes in each jurisdiction.

PMID- 22632098
TI  - Simulations of SIN Mutations and Histone Variants in Human Nucleosomes Reveal
      Altered Protein-DNA and Core Histone Interactions.
AB  - Abstract   Alterations in the stability of a nucleosome exert predominant
      influence on chromatin structure and eukaryotic gene expression. In an attempt to
      investigate the mononucleosome stability using computational approaches, we have
      simulated the structure of a human mononucleosome and have compared their
      energies under the influence of core mutations, tail substitutions, variant
      histones, and orthologs. We observe that mutant nucleosomes carrying SIN (SWI
      Independent) mutations do not alter the overall nucleosomal structure but cause
      local structural changes leading to significant changes in energy and hence the
      stability. We observe that the nucleosome stability is altered by the
      substitution of only certain critical lysine residues on the H3 tails.
      Interestingly, the incorporation of variants H2A.Z and H3.3 lower nucleosome
      stability as evidenced by small energy changes. However, the substitution of
      histone orthologs did not alter structural stability. Our simulations to
      determine the nucleosome stability using energy trends emphasize the role of
      mutations, variants, and orthologs as determinants of chromatin structure at the
      nucleosome core particle level. The de-stabilization we observe on the human
      nucleosome with core mutations show similar trends of instability as validated
      experimentally in yeast.

PMID- 22632099
TI  - Induction phase, primary endpoint, time to decide on primary failure, and
      therapeutic goals in biologic treatment of psoriasis.

PMID- 22632100
TI  - Early do-not-resuscitate orders in intracerebral haemorrhage; frequency and
      predictive value for death and functional outcome. A retrospective cohort study.
AB  - INTRODUCTION: In former studies from North America early Do-Not-Resuscitate
      orders (DNR orders) in patients with intracerebral haemorrhage (ICH) had negative
      prognostic impact on mortality. The influence of DNR orders on functional outcome
      and whether DNR orders are grounded on relevant patient characteristics is
      unknown. We aimed to determine the frequency and predictive factors of DNR-orders
      and its association to prognosis, in ICH patients, in Scandinavia. METHODS: In
      197 consecutive ICH patients admitted to Skane University Hospital, Malmo,
      Sweden, between January 2007 and June 2009, information of the presence of DNR
      orders within 48 hours, clinical and radiological characteristics was retrieved
      by review of patient medical journal and computed tomography scans. Determinants
      of DNR-orders, one-month case fatality and bad functional outcome (modified
      Rankin Scale, grade 4-6) were assessed by logistic regression analysis. RESULTS:
      DNR orders were made in 41% of the cases. After adjustment for confounding
      factors, age >= 75 years (Odds Ratio (95% confidence interval) 4.2(1.8-9.6)),
      former stroke (5.1(1.9-3.1)), Reaction Level Scale grade 2-3 and 4 (7.0(2.8-17.5)
      and (4.1(1.2-13.5), respectively) and intraventricular haemorrhage (3.8(1.6-9.4))
      were independent determinants of early DNR orders. Independent predictors of one
      month case fatality was age >= 75 years (3.7(1.4-9.6)) volume >= 30 ml (3.5(1.3
      9.6)) and DNR orders (3.5(1.5-8.6)). Seizure (6.0(1.04-34.2) and brain stem
      hemorrhage (8.0(1.1-58.4)) were related to bad functional outcome, whereas early
      DNR order was not (3.5(0.99-12.7)). CONCLUSIONS: Well known prognostic factors
      are determinants for DNR orders, however DNR orders are independently related to
      one-month case fatality. In addition to improvements of the local routines, we
      welcome a change of attitude with an enhanced awareness of the definition of, and
      a more careful approach with respect to DNR orders.

PMID- 22632101
TI  - Preparation of supercapacitor electrodes through selection of graphene surface
      functionalities.
AB  - In order to investigate the effect of graphene surface chemistry on the
      electrochemical performance of graphene/polyaniline composites as supercapacitor
      electrodes, graphene oxide (G-O), chemically reduced G-O (RG-O), nitrogen-doped
      RG-O (N-RG-O), and amine-modified RG-O (NH(2)-RG-O) were selected as carriers and
      loaded with about 9 wt % of polyaniline (PANi). The surface chemistry of these
      materials was analyzed by FTIR, NEXAFS, and XPS, and the type of surface
      chemistry was found to be important for growth of PANi that influences the
      magnitude of increase of specific capacitance. The NH(2)-RG-O/PANi composite
      exhibited the largest increase in capacitance with a value as high as 500 F g(-1)
      and good cyclability with no loss of capacitance over 680 cycles, much better
      than that of RG-O/PANi, N-RG-O/PANi, and G-O/PANi when measured in a three
      electrode system. A NH(2)-RG-O/PANi//N-RG-O supercapacitor cell has a capacitance
      of 79 F g(-1), and the corresponding specific capacitance for NH(2)-RG-O/PANi is
      395 F g(-1). This research highlights the importance of introducing -NH(2) to RG
      O to achieve highly stable cycling performance and high capacitance values.

PMID- 22632102
TI  - Colon-specific delivery of celecoxib is a potential strategy to improve
      toxicological and pharmacological properties of the selective Cox-2 inhibitor:
      implication in treatment of familiar adenomatous polyposis.
AB  - In general, colon-specific delivery of a drug decreases systemic absorption and
      increases therapeutic concentration of the drug at the target site. N
      succinylglutam-1 or 5-yl celecoxib (SG1C and SG5C) were prepared as a colon
      specific prodrug of celecoxib, a selective Cox-2 inhibitor, and investigated
      whether the celecoxib derivatives could deliver celecoxib to the target site and
      improve cardiovascular toxicity and therapeutic effectiveness for the treatment
      of familiar adenomatous polyposis. SG1C and SA5C were cleaved to release
      celecoxib in the cecal contents while stable in small intestinal contents. The
      cecal release of celecoxib was much greater for SG1C than SG5C. SG1C administered
      orally was barely detected in the blood and urine. SG1C delivered much greater
      amount of celecoxib to the large intestine while keeping the plasma concentration
      of celecoxib at much lower level compared with oral administration of free
      celecoxib. Consistent with these pharmacokinetic results, SG1C supplied a greater
      concentration of celecoxib for the entire colonic tissue and did not change the
      serum level of 6-keto-PGF(1alpha) whose decrease is associated with the
      cardiovascular toxicity of celecoxib. Taken together, colon-specific delivery of
      celecoxib using a prodrug approach may be a useful strategy to improve
      toxicological and pharmacological properties of celecoxib.

PMID- 22632103
TI  - Correlations among symptoms, signs, and clinical tests in evaporative-type dry
      eye disease caused by Meibomian gland dysfunction (MGD).
AB  - PURPOSE: To evaluate changes in symptoms, objective tests, and signs after
      medical treatment of subjects with evaporative-type dry eye disease (EDE) caused
      by Meibomian gland dysfunction (MGD), and to analyze correlations among symptoms,
      signs and test results in the worse eyes (W-eyes) of the subjects. METHODS:
      Prospective clinical study of 21 symptomatic subjects with EDE caused by MGD.
      Subjects who were diagnosed with EDE in a first visit were treated for 6 weeks
      and re-evaluated in a second visit. The differences between initial and second
      visits were evaluated. Correlations among clinical symptoms, signs, and test
      results were performed using the data of the W-eyes. Variables evaluated
      included: dry eye symptoms, best corrected visual acuity (BCVA), contrast
      sensitivity, conjunctival hyperemia, phenol red thread test, tear break-up time
      (TBUT), tear meniscus height (TMH), corneal fluorescein and conjunctival rose
      Bengal staining, tear lysozyme concentration, Schirmer test, and lid margin
      assessment. RESULTS: All items evaluated improved after treatment, but only
      conjunctival hyperemia and TMH improved significantly. TBUT and lid margin
      changes improved, but still remained abnormal. There were significant
      correlations among symptoms questionnaires and some clinical tests (TBUT,
      conjunctival hyperemia, TMH, and conjunctival rose Bengal staining). CONCLUSION:
      Despite the instability of the tear film and lid margin alterations that
      continued after treatment, subjects with MGD improved symptomatically. The low
      degree of correlations among W-eye signs, symptoms, and tests reflects the
      independency of symptoms and signs in this complex pathology.

PMID- 22632105
TI  - Molecular insights into the effects of sodium hyaluronate preparations in
      keratinocytes.
AB  - BACKGROUND: Hyaluronic acid (HA) preparations are widely used in clinical
      practice to accelerate wound healing, but it is not clear whether HA can exert
      direct effects on epidermal keratinocytes. AIM: To investigate the molecular and
      functional changes induced by HA preparations in keratinocytes by measuring
      global gene expression and wound healing. METHODS: Human skin keratinocytes were
      used for this study. They were treated with either sodium hyaluronate (SH) alone
      or a commercial adjuvant gel (Aminogam((r))) containing SH in combination with a
      pool of synthetic amino acids (L-proline, L-leucine, L-lysine and glycine).
      Global gene expression of nearly 55,000 transcripts was investigated with a chip
      array (Affymetrix Human Genome U133 2.0 Plus). RESULTS: We found that
      keratinocytes expressed all major HA receptors at the transcriptional level. In a
      fibroblast-free system, both SH and the adjuvant gel could effectively promote
      wound healing of keratinocytes. Major gene expression changes induced by HA
      preparations involves proteolysis, proteinase inhibitors, cellular metabolism and
      cytoskeleton. In total, 21 genes were differentially transcribed by SH and the
      adjuvant gel. CONCLUSIONS: Keratinocytes represent a previously underestimated
      target for HA action in wound healing. HA preparations induce transcriptional
      changes in keratinocytes and stimulate wound closure. Furthermore, the addition
      of synthetic amino acids to SH induces a distinct transcriptional profile.

PMID- 22632106
TI  - A win-win solution in oral delivery of lipophilic drugs: supersaturation via
      amorphous solid dispersions increases apparent solubility without sacrifice of
      intestinal membrane permeability.
AB  - Recently, we have revealed a trade-off between solubility increase and
      permeability decrease when solubility-enabling oral formulations are employed. We
      have shown this trade-off phenomenon to be ubiquitous, and to exist whenever the
      aqueous solubility is increased via solubilizing excipients, regardless if the
      mechanism involves decreased free fraction (cyclodextrins complexation,
      surfactant micellization) or simple cosolvent solubilization. Discovering a way
      to increase drug solubility without concomitant decreased permeability represents
      a major advancement in oral delivery of lipophilic drugs and is the goal of this
      work. For this purpose, we sought to elucidate the solubility-permeability
      interplay when increased apparent solubility is obtained via supersaturation from
      an amorphous solid dispersion (ASD) formulation. A spray-dried ASD of the
      lipophilic drug progesterone was prepared in the hydrophilic polymer
      hydroxypropyl methylcellulose acetate succinate (HPMC-AS), which enabled
      supersaturation up to 4* the crystalline drug's aqueous solubility (8 MUg/mL).
      The apparent permeability of progesterone from the ASD in HPMC-AS was then
      measured as a function of increasing apparent solubility (supersaturation) in the
      PAMPA and rat intestinal perfusion models. In contrast to previous cases in which
      apparent solubility increases via cyclodextrins, surfactants, and cosolvents
      resulted in decreased apparent permeability, supersaturation via ASD resulted in
      no decrease in apparent permeability with increasing apparent solubility. As a
      result, overall flux increased markedly with increasing apparent solubility via
      ASD as compared to the other formulation approaches. This work demonstrates that
      supersaturation via ASDs has a subtle yet powerful advantage over other
      solubility-enabling formulation approaches. That is, increased apparent
      solubility may be achieved without the expense of apparent intestinal membrane
      permeability. Thus, supersaturation via ASDs presents a markedly increased
      opportunity to maximize overall oral drug absorption. 

PMID- 22632107
TI  - Automatic processes in at-risk adolescents: the role of alcohol-approach
      tendencies and response inhibition in drinking behavior.
AB  - AIMS: This study examined the association between automatic processes and
      drinking behavior in relation to individual differences in response inhibition in
      young adolescents who had just started drinking. It was hypothesized that strong
      automatic behavioral tendencies toward alcohol-related stimuli (alcohol-approach
      bias) were associated with higher levels of alcohol use, especially amongst
      adolescents with relatively weak inhibition skills. DESIGN: To test this
      hypothesis structural equation analyses (standard error of mean) were performed
      using a zero inflated Poisson (ZIP) model. A well-known problem in studying risk
      behavior is the low incidence rate resulting in a zero dominated distribution. A
      ZIP-model accounts for non-normality of the data. SETTING: Adolescents were
      selected from secondary Special Education schools (a risk group for the
      development of substance use problems). PARTICIPANTS: Participants were 374
      adolescents (mean age of M = 13.6 years). MEASUREMENTS: Adolescents completed the
      alcohol approach avoidance task (a-AAT), the Stroop colour naming task (Stroop)
      and a questionnaire that assessed alcohol use. FINDINGS: The ZIP-model
      established stronger alcohol-approach tendencies for adolescent drinkers (P <
      0.01) and the interaction revealed a stronger effect of alcohol-approach
      tendencies on alcohol use in the absence of good inhibition skills (P < 0.05).
      CONCLUSION: Automatically-activated cognitive processes are associated with the
      drinking behavior of young, at-risk adolescents. It appears that alcohol-approach
      tendencies are formed shortly after the initiation of drinking and particularly
      affect the drinking behavior of adolescents with relatively weak inhibition
      skills. Implications for the prevention of problem drinking in adolescents are
      discussed.

PMID- 22632108
TI  - Hypoxia-inducible factor-1alpha expression indicates poor prognosis in
      myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS), which are clonal bone marrow malignancies
      characterized by ineffective hematopoiesis, incorporate a variety of disorders
      and have variable prognosis. Although the International Prognostic Scoring System
      (IPSS) provides a clinical model for risk stratification of patients with primary
      MDS, notable variability in prognosis is still observed within the same IPSS
      category. Hypoxia-inducible factor-1alpha (HIF-1alpha) is associated with an
      adverse prognosis in patients with solid tumors and some hematological
      malignancies. However, the relationship between HIF-1alpha and clinical outcomes
      of patients with MDS is unknown. We examined HIF-1alpha by immunohistochemistry
      in bone marrow specimens from 81 patients with MDS. Results showed that the
      expression rate of HIF-1alpha was 49.4% (40/81). Multivariate analysis including
      age, bone marrow blast percentage, cytogenetics, hemoglobin, white blood cell
      count and IPSS score demonstrated that HIF-1alpha (p = 0.049, HR = 2.704) was an
      independent prognostic indicator for MDS. Furthermore, the expression of HIF
      1alpha was correlated with poor overall survival (p < 0.001) and disease
      progression (p = 0.004). In addition, correlation analysis revealed that the
      expression of HIF-1alpha was associated with bone marrow blast percentage (p <
      0.001, r = 0.510), hemoglobin count (p < 0.001, r = 0.649) and cytogenetics (p =
      0.009, r = 0.287). We also found that decitabine achieved a better therapeutic
      effect compared to traditional chemotherapy in HIF-1alpha positive patients. In
      conclusion, these results suggest that HIF-1alpha is a vital biomarker for
      predicting the progression and prognosis of MDS.

PMID- 22632109
TI  - A randomised trial of robotic and open prostatectomy in men with localised
      prostate cancer.
AB  - BACKGROUND: Prostate cancer is the most common male cancer in the Western world
      however there is ongoing debate about the optimal treatment strategy for
      localised disease. While surgery remains the most commonly received treatment for
      localised disease in Australia more recently a robotic approach has emerged as an
      alternative to open and laparoscopic surgery. However, high level data is not yet
      available to support this as a superior approach or to guide treatment decision
      making between the alternatives. This paper presents the design of a randomised
      trial of Robotic and Open Prostatectomy for men newly diagnosed with localised
      prostate cancer that seeks to answer this question. METHODS/DESIGN: 200 men per
      treatment arm (400 men in total) are being recruited after diagnosis and before
      treatment through a major public hospital outpatient clinic and randomised to 1)
      Robotic Prostatectomy or 2) Open Prostatectomy. All robotic prostatectomies are
      being performed by one surgeon and all open prostatectomies are being performed
      by one other surgeon. Outcomes are being measured pre-operatively and at 6 weeks
      and 3, 6, 12 and 24 months post-surgery. Oncological outcomes are being related
      to positive surgical margins, biochemical recurrence +/- the need for further
      treatment. Non-oncological outcome measures include: pain, physical and mental
      functioning, fatigue, summary (preference-based utility scores) and domain
      specific QoL (urinary incontinence, bowel function and erectile function), cancer
      specific distress, psychological distress, decision-related distress and time to
      return to usual activities. Cost modelling of each approach, as well as full
      economic appraisal, is also being undertaken. DISCUSSION: The study will provide
      recommendations about the relative benefits of Robotic and Open Prostatectomy to
      support informed patient decision making about treatment for localised prostate
      cancer; and to assist in treatment services planning for this patient group.
      TRIAL REGISTRATION: ACTRN12611000661976.

PMID- 22632110
TI  - Vigabatrin-associated retinal damage: potential biochemical mechanisms.
AB  - Vigabatrin (VGB), an irreversible inhibitor of gamma-aminobutyric acid (GABA)
      transaminase, is approved as adjunct treatment of refractory partial seizures as
      well as infantile spasms. Although VGB has been proven to be effective, its use
      is limited by the risk of retinopathy and associated peripheral visual field
      defects. This review describes and analyzes current literature related to
      potential pathophysiologic mechanisms underlying VGB-mediated cellular toxicity.
      Animal data suggest that GABA mediates neural excitotoxicity. The amino acid
      taurine is concentrated in retinal cells, and deficiency of this amino acid may
      be involved in VGB-mediated retinal degeneration and possible phototoxicity.

PMID- 22632111
TI  - Pressure effects on enzyme-catalyzed quantum tunneling events arise from protein
      specific structural and dynamic changes.
AB  - The rate and kinetic isotope effect (KIE) on proton transfer during the aromatic
      amine dehydrogenase-catalyzed reaction with phenylethylamine shows complex
      pressure and temperature dependences. We are able to rationalize these effects
      within an environmentally coupled tunneling model based on constant pressure
      molecular dynamics (MD) simulations. As pressure appears to act anisotropically
      on the enzyme, perturbation of the reaction coordinate (donor-acceptor
      compression) is, in this case, marginal. Therefore, while we have previously
      demonstrated that pressure and temperature dependences can be used to infer H
      tunneling and the involvement of promoting vibrations, these effects should not
      be used in the absence of atomistic insight, as they can vary greatly for
      different enzymes. We show that a pressure-dependent KIE is not a definitive
      hallmark of quantum mechanical H-tunneling during an enzyme-catalyzed reaction
      and that pressure-independent KIEs cannot be used to exclude tunneling
      contributions or a role for promoting vibrations in the enzyme-catalyzed
      reaction. We conclude that coupling of MD calculations with experimental rate and
      KIE studies is required to provide atomistic understanding of pressure effects in
      enzyme-catalyzed reactions.

PMID- 22632112
TI  - Bovine trophoblastic cell differentiation and binucleation involves enhanced
      endogenous retrovirus element expression.
AB  - BACKGROUND: Endogenous retrovirus (ERV) envelope (env) genes are involved in the
      differentiation of trophoblastic cells in humans and mice. However, there is
      limited information about their roles in ruminant trophoblastic cells. Thus, we
      attempted to explore the possible roles of ERV elements in the binucleation of
      bovine trophoblastic cells using in vitro bovine trophoblastic (BT) cell lines.
      METHODS: In this study, blastocysts and elongated embryos were obtained from
      Japanese Black cows, and endometrial and fetal membrane tissues were collected
      from day 17 to 37 of gestation. The gene expression levels of four ERV elements,
      bERVE (bovine endogenous retrovirus envelope element-like transcript) -A, bERVE
      B, BERV (bovine endogenous retrovirus) -K1 env, and BERV-K2 env, were analyzed in
      the fetal and endometrial tissue and cultured BT cell lines using quantitative RT
      PCR. On-Matrigel gel and on-collagen gel culturing were used to induce binucleate
      cell (BNC) formation in the BT cell lines. How the culture conditions affected
      the expression of BNC-specific genes and ERV elements was examined by
      quantitative RT-PCR and immunocytochemistry. RESULTS: bERVE-A, bERVE-B, BERV-K1
      env, and BERV-K2 env were expressed in almost all BT cell lines; however, only
      bERVE-A and BERV-K1 env were detected in trophoblastic tissues during the peri
      implantation period. In the on-Matrigel cultures, the expression levels of BNC
      specific genes and molecules were enhanced in the BT cells. The expression levels
      of bERVE-A and BERV-K1 env were also increased in the BT cells during on-Matrigel
      culturing. The BT cell expression levels of these ERV elements were consistent
      with those of BNC-specific genes during on-Matrigel culturing (P < 0.01).
      CONCLUSIONS: These results suggest that bERVE-A and BERV-K1 env are involved in
      the expression of BNC-specific genes and the progression of bovine trophoblastic
      cell binucleation, as their expression levels increased during periods of
      increased BNC-specific molecule expression, which is strongly suggestive of the
      development of BNC from mononucleate trophoblastic cells. The on-Matrigel culture
      system is a convenient in vitro tool for studying bovine trophoblastic cell
      lineages.

PMID- 22632113
TI  - Flexibility regeneration of silk fibroin in vitro.
AB  - Although natural silk fibers have excellent strength and flexibility, the
      regenerated silk materials generally become brittle in the dry state. How to
      reconstruct the flexibility for silk fibroin has bewildered scientists for many
      years. In the present study, the flexible regenerated silk fibroin films were
      achieved by simulating the natural forming and spinning process. Silk fibroin
      films composed of silk I structure were first prepared by slow drying process.
      Then, the silk fibroin films were stretched in the wet state, following the
      structural transition from silk I to silk II. The difference between the flexible
      film and different brittle regenerated films was investigated to reveal the
      critical factors in regulating the flexibility of regenerated silk materials.
      Compared with the methanol-treated silk films, although having similar silk II
      structure and water content, the flexible silk films contained more bound water
      rather than free water, implying the great influence of bound water on the
      flexibility. Then, further studies revealed that the distribution of bound water
      was also a critical factor in improving silk flexibility in the dry state, which
      could be regulated by the nanoassembly of silk fibroin. Importantly, the results
      further elucidate the relation between mechanical properties and silk fibroin
      structures, pointing to a new mode of generating new types of silk materials with
      enhanced mechanical properties in the dry state, which would facilitate the
      fabrication and application of regenerated silk fibroin materials in different
      fields.

PMID- 22632121
TI  - Predictors and impact of microsurgical complications in patients with locally
      advanced oral squamous cell carcinoma.
AB  - Microvascular free flap transfer for post-oncologic reconstructive surgery in
      oral cancer is considered to be a challenge due to the complexity of the anatomy
      and function of the region. We sought to identify possible factors associated
      with microsurgical complications and to assess the impact of these complications
      in relation to patient survival. Following the inclusion and exclusion protocol,
      142 patients with stage III and IV oral squamous cell carcinoma (OSCC) who
      underwent immediate free flap reconstruction after tumor ablation were included
      in the study. Clinical and surgical procedural-related factors were retrieved
      from a database and analyzed retrospectively; survival data were evaluated using
      the Kaplan-Meier method. Major complications that required re-anastomosis of the
      flap vessels occurred in 23 patients (16.2%); total necrosis of the flaps,
      regardless of salvage treatment, occurred in seven cases, with 95.1% of full flap
      survival. The American Society of Anesthesiologists classification, types of neck
      dissection, and number of flaps were regarded as strong predictors for surgical
      complications. Patients with these complications appeared to have a shortened
      survival (5-year cancer-specific survival of approximately 60%, both in stage III
      and IV OSCC). However, the impact of surgical complications on survival was
      significant only in stage III OSCC (P = 0.037). Strategies to minimize surgical
      complications should be used to ensure better prognoses for these patients.

PMID- 22632122
TI  - Factors affecting solubilization of a poorly soluble novel tubulin-binding agent.
AB  - JCA112 is a novel tubulin-binding agent with limited aqueous solubility and high
      hydrophobicity. Three strategies; cyclodextrin inclusion complexation, solid
      dispersion (SD) formation, and liposome incorporation were evaluated to enhance
      the solubility of JCA112. Phase-solubility studies were carried out with
      hydroxypropyl beta-cyclodextrin (HPbetaCD), SDs were prepared by solvent
      evaporation method and liposomes were prepared by thin-film hydration method.
      Saturation solubility of the prepared formulations resulted in a significant
      increase in the solubility of JCA112 by all three methods. Cyclodextrin
      complexation resulted in a higher order complex formation increasing the aqueous
      solubility by 30-fold up to 105 MUg/mL. Amongst the selected polymers, Poloxamer
      188 (Pluronic((r)) F68) was the most effective polymer in enhancing the aqueous
      solubility via SD, resulting in an equilibrium solubility of 50 MUg/mL,
      independent of the drug loading. Liposomes were the most effective amongst all
      three techniques, with a saturation solubility of 1.8 mg/mL contributing to
      greater than 500-fold increase in the solubility of JCA112. The solubility
      enhancement by liposome was directly proportional to the drug loading. All the
      three strategies were successful in enhancing the solubility of the drug.
      Solubility enhancement by the three techniques can be attributed to the
      geometry/structure and the lipophilicity of the drug. 

PMID- 22632123
TI  - Lignan and flavonoid phytoestrogens from the seeds of Cuscuta chinensis.

PMID- 22632125
TI  - Evidence of cis-acting regulatory variation in PTPN22 in patients with rheumatoid
      arthritis.
AB  - OBJECTIVES: To assess whether there are cis-regulatory polymorphisms that
      regulate protein tyrosine phosphatase, non-receptor type 22 (PTPN22) expression
      in rheumatoid arthritis (RA). METHODS: RNA was extracted from positively selected
      CD56+, CD8+, and CD4+ mononuclear cells and the 'residual' cells from 12 RA
      patients heterozygous for the PTPN22 C1858T single nucleotide polymorphism (SNP)
      (rs2476601). Relative allelic expression was measured by single base extension
      (SBE) assay. RESULTS: There was relative differential allelic expression (DAE >=
      20%) in eight patients (p < 10(-5)); seven patients demonstrated DAE in more than
      one cell type; four patients had statistically significant differences between
      these cell populations (p(corrected) < 0.05). CONCLUSIONS: We have demonstrated
      significant differences in expression of PTPN22 alleles in RA patients,
      indicating the probable existence of cis-acting regulatory elements.

PMID- 22632124
TI  - Repression of bacterial lipoprotein production by Francisella novicida
      facilitates evasion of innate immune recognition.
AB  - Innate recognition systems, including the Toll-like receptors (TLRs), play a
      critical role in activating host defences and proinflammatory pathways in
      response to infection. Pathogens have developed strategies to subvert TLRs in
      order to survive and replicate within the host. The model intracellular pathogen,
      Francisella novicida, modulates host defences to promote survival and replication
      in macrophages. TLR2, which recognizes bacterial lipoproteins (BLPs), is critical
      for activating host defences and proinflammatory cytokine production in response
      to Francisella infection. Here we show that the F. novicida protein FTN_0757 acts
      to repress BLP production, dampening TLR2 activation. The DeltaFTN_0757 mutant
      strain induced robust TLR2-dependent cytokine production in macrophages compared
      with wild-type bacteria, and produced increased amounts of BLPs. The deletion of
      one BLP (FTN_1103) from DeltaFTN_0757 decreased the total BLP concentration to
      near wild-type level sand correlated with a decrease in the inductionof TLR2
      signalling. The overproduction of BLPs also contributed to the in vivo
      attenuation of the DeltaFTN_0757 mutant, which was significantly rescued when
      FTN_1103 was deleted. Taken together, these data reveal a novel mechanism of
      immune evasion by the downregulation of BLP expression to subvert TLR2
      activation, which is likely used by numerous other intracellular bacterial
      pathogens.

PMID- 22632128
TI  - Hollow nanoneedle array and its utilization for repeated administration of
      biomolecules to the same cells.
AB  - We present a novel hollow nanoneedle array (NNA) device capable of simultaneously
      delivering diverse cargo into a group of cells in a culture over prolonged
      periods. The silica needles are fed by a common reservoir whose content can be
      replenished and modified in real time while maintaining contact with the same
      cells. The NNA, albeit its submicrometer features, is fabricated in a silicon-on
      insulator wafer using conventional, large scale, silicon technology. 3T3-NIH
      fibroblast cells and HEK293 human embryonic kidney cells are shown to grow and
      proliferate successfully on the NNAs. Cargo delivery from the reservoir through
      the needles to a group of HEK293 cells in the culture is demonstrated by repeated
      administration of fluorescently labeled dextran to the same cells and
      transfection with DNA coding for red fluorescent protein. The capabilities
      demonstrated by the NNA device open the door to large scale studies of the effect
      of selected cells on their environment as encountered, for instance, in the study
      of cell-fate decisions, the role of cell-autonomous versus nonautonomous
      mechanisms in developmental biology, and in the study of excitable cell-networks.

PMID- 22632126
TI  - Towards prevention of acute lung injury: frequency and outcomes of emergency
      department patients at-risk - a multicenter cohort study.
AB  - BACKGROUND: Few emergency department (ED) evaluations on acute lung injury (ALI)
      have been carried out; hence, we sought to describe a cohort of hospitalized ED
      patients at risk for ALI development. METHODS: Patients presenting to the ED with
      at least one predisposing condition to ALI were included in this study, a
      subgroup analysis of a multicenter observational cohort study (USCIITG-LIPS 1).
      Patients who met ALI criteria within 6 h of initial ED assessment, received end
      of-life care, or were readmitted during the study period were excluded. Primary
      outcome was frequency of ALI development; secondary outcomes were ICU and
      hospital mortality. RESULTS: Twenty-two hospitals enrolled 4,361 patients who
      were followed from the ED to hospital discharge. ALI developed in 303 (7.0 %)
      patients at a median onset of 2 days (IQR 2-5). Of the predisposing conditions,
      frequency of ALI development was highest in patients who had aortic surgery (43
      %) and lowest in patients with pancreatitis (2.8 %). Compared to patients who did
      not develop ALI, those who did had higher ICU (24 % vs. 3.0 %, p < 0.001) and
      hospital (28 % vs. 4.6 %, p < 0.001) mortality, and longer hospital length of
      stay (16 vs. 5 days, p < 0.001). Among the 22 study sites, frequency of ALI
      development varied from less than 1 % to more than 12 % after adjustment for
      APACHE II. CONCLUSIONS: Seven percent of hospitalized ED patients with at least
      one predisposing condition developed ALI. The frequency of ALI development varied
      significantly according to predisposing conditions and across institutions.
      Further research is warranted to determine the factors contributing to ALI
      development.

PMID- 22632127
TI  - Short communication: factors influencing time to CD4(+) T cell counts >200
      cells/mm(3) in HIV-infected individuals with CD4(+) T cell <50 cells/mm(3) at the
      time of starting combination antiretroviral therapy.
AB  - We evaluated factors influencing time to CD4(+) T cell counts >200 cells/mm(3) in
      HIV-infected individuals with CD4(+) T cell <50 cells/mm(3) starting combination
      antiretroviral therapy (cART). We included a total of 29 patients on successful
      cART for more than 1 year. In a logistic regression model, higher pre-cART CD4(+)
      T cell counts were significantly associated with shorter time to CD4(+) T cell
      counts >200cells/mm(3) in HIV-infected individuals with baseline CD4(+) T cell
      <50 cells/mm(3). In survival analysis, patients having higher pre-cART CD4(+) T
      cell counts, especially 40-49 cells/mm(3), were at significantly higher risk of
      achieving CD4(+) T cell counts >200 cells/mm(3).

PMID- 22632129
TI  - Bizarre electrocardiographic changes during occlusion of a congenital coronary
      arteriovenous fistula.
AB  - A 38-year-old man who had a history of percutaneous coronary artery coil
      occlusion was admitted to our hospital with chest pain and shortness of breath.
      His complaint was chest pain, which is typical. ST depressions were observed
      during the treadmill exercise stress test. Coronary angiography demonstrated the
      persistence of a coronary arteriovenous fistula and coils in the fistula.
      Primarily, additional coil placement inside the arteriovenous fistula was decided
      as the mode of treatment. The coil was first placed inside the arteriovenous
      fistula and then an attempt was made to detach it. However, it was unsuccessful
      after four trials and electrical detachment of more than 3 minutes. Finally, a
      2.5 * 18-millimetre graft stent was deployed at 20 atmospheric pressure.
      Electrocardiographic recordings showed bizarre ST segment changes during the
      electrical detachment of the coil. In this report, we discuss the concealed
      bizarre electrocardiographic changes that were seen during coronary arteriovenous
      fistula occlusion.

PMID- 22632130
TI  - The effect of time between venipuncture, processing and freezing on the
      measurement of coagulation factor levels.

PMID- 22632131
TI  - Inflammation imaging by silica nanoparticles with antibodies orientedly
      immobilized.
AB  - The objective of this study is to design fluorescent nanoprobes for inflammation
      imaging. An antibody against CD11b expressed on the surfaces of mouse macrophages
      (anti-CD11b), was fluorescently labeled. Protein G, which has an ability to bind
      the Fc region of antibody, was conjugated onto the surface of silica
      nanoparticles (SiNP). Then, the fluorescent-labeled anti-CD11b was orientedly
      immobilized to the SiNP surface through the specific protein G-antibody
      interaction. After the intravenous injection of anti-CD11b orientedly immobilized
      SiNP to the mouse model of acute interstitial nephritis, unilateral ureteral
      obstruction (UUO) of one kidney, the fluorescent intensity at the UUO and non
      treated, normal kidneys was assessed. The anti-CD11b orientedly immobilized SiNP
      were accumulated in the UUO kidney to a significantly great extent compared with
      the normal, non-inflamed kidney. The fluorescence intensity of inflamed kidney 6
      and 12 h after injection of the anti-CD11b orientedly immobilized SiNP were
      significantly higher than that of anti-CD11b randomly immobilized SiNP or free
      anti-CD11b injection. Histological experiments revealed that the anti-CD11b
      orientedly immobilized SiNP were associated with macrophages infiltrated into the
      inflammation site. It is concluded that the anti-CD11b orientedly immobilized
      SiNP are promising nanoprobes to image the inflammation site at a high intensity.

PMID- 22632132
TI  - Licensing of killer dendritic cells in mouse and humans: functional similarities
      between IKDC and human blood gammadelta T-lymphocytes.
AB  - Dendritic cells are characterized by the ability to induce primary antigen
      specific immune responses in both major histocompatibility complex (MHC) Class I
      restricted CD8 cells and MHC Class II-restricted CD4 cells. This professional
      antigen presentation function is associated with the up-regulation of co
      stimulatory molecules and Class II MHC. While it has been recognized that several
      types of innate lymphocytes in mouse and humans can express co-stimulatory
      molecules and present antigen, the property of antigen presentation to elicit
      responses in naive cells has been considered the exclusive domain of the
      dendritic cell. This concept has been challenged through the description of
      innate lymphocytes, capable of killing using NK receptors, but also up-regulating
      co-stimulatory molecules and driving the antigen-specific proliferation of naive
      lymphocytes to the same extent as dendritic cells. Interferon (IFN)-gamma
      secreting killer dendritic cells (IKDC) have been described in mice and share
      immunophenotypic properties of both dendritic cells and natural killer cells.
      Human blood gammadelta T-lymphocytes have innate tumor cell killing properties by
      both antibody-dependent and natural killer receptor-dependent mechanisms. This
      article reviews data from the authors' own laboratory showing a particular
      feature in common between the mouse IKDC and human blood gammadelta T
      lymphocytes; namely their requirement for interaction with a target cell for
      specific licensing for professional antigen presentation.

PMID- 22632133
TI  - Galactokinase deficiency induced cataracts in Indian infants: identification of 4
      novel mutations in GALK gene.
AB  - PURPOSE: To establish the incidence and molecular basis of type II galactosemia
      in Indian infants presenting with congenital cataracts. METHODS: 200 infants with
      congenital cataracts were screed for galactokinase (GALK) enzyme deficiency. GALK
      enzyme activity was measured using radioactive galactose-1-(14)C and mutations
      were studied using polymerase chain reaction (PCR), single strand conformational
      polymorphism (SSCP) and subsequent DNA sequencing. RESULTS: 16 (8%) out of 200
      infants with congenital cataracts were found to be GALK deficient with male:
      female:: 9:7. A significantly reduced GALK activity of 0.13 +/- 0.04 umoles/h/mL
      was observed in the galactosemia patients compared to 0.232 +/- 0.07 umoles/h/mL
      in the normal controls. A total of 5 distinct mutations were identified in GALK
      gene in five different patients out of which four were novel mutations viz. S79F,
      S79Y, S205S and F275Y. The functional significance of the mutations and splicing
      defects associated with them were investigated using different computer based
      applications. CONCLUSION: The study highlighted the importance of GALK gene
      analysis in diagnosis of galactosemia in Indian population. It also revealed that
      the mutational profile of Indian GALK patients differs significantly from other
      populations studied. Low mutation detection rate observed in this study may be
      due to the fact that SSCP is a quite indirect and non-fullproof method of
      mutation detection.

PMID- 22632134
TI  - Student midwives' views on maternity care just before their graduation.
AB  - AIM: To report a hermeneutic study of student midwives' views on maternity care
      just before their graduation. background: Woman-centred care, which is the
      hallmark of midwifery, is taught to midwifery students around the globe. Woman
      centred care is advantageous for women at low obstetric risk. However, adopting
      this ideology might be a problem for student midwives whose clinical placements
      are mainly in a medicalized obstetric-led hospital setting. DESIGN: A hermeneutic
      phenomenological study was conducted. METHODS: In 2010, three focus groups were
      held where 19 student midwives participated. Data were transcribed verbatim and
      analysed using van Manen's approach. FINDINGS: The choice for midwifery was a
      'positive' choice and not the result of an elimination process. Students'
      description of a midwife as a coach was in line with the international definition
      of a midwife. With regard to maternity care, midwifery students identified two
      types of care, factory-style care and tailored care, both of which were ascribed
      to caregivers and hospital culture. Furthermore, student midwives made the
      distinction between hierarchy and teamwork, referring to the professional
      relations in maternity care. Hierarchy was driven by tradition, it implied that
      decisions were made top-down, and it resulted in impersonal relations. Midwifery
      students felt it was unjust that midwives were not allowed to perform deliveries
      while having the legal autonomy to do so. CONCLUSION: In spite of the medicalized
      context, midwifery education succeeded in educating midwives who hold a woman
      centred ideology. Midwifery students linked style of care to a person rather than
      to a profession.

PMID- 22632135
TI  - Effect of a psycho-educational intervention for family members on caregiver
      burdens and psychiatric symptoms in patients with schizophrenia in Shiraz, Iran.
AB  - BACKGROUND: This study explored the effectiveness of family psycho-education in
      reducing patients' symptoms and on family caregiver burden. METHODS: Seventy
      Iranian outpatients with a diagnosis of schizophrenia disorder and their
      caregivers were randomly allocated to the experimental (n = 35) or control groups
      (n = 35). Patients in the experimental group received antipsychotic drug
      treatment and a psycho-educational program was arranged for their caregivers. The
      psycho-educational program consisted of ten 90-min sessions held during five
      weeks (two session in each week). Each caregiver attended 10 sessions (in five
      weeks) At baseline, immediately after intervention, and one month later.
      Validated tools were used to assess patients' clinical status and caregiver
      burden. RESULTS: Compared with the control group, the case group showed
      significantly reduced symptom severity and caregiver burden both immediately
      after intervention and one month later. CONCLUSIONS: These results suggest that
      even need based short-term psycho-educational intervention for family members of
      Iranian patients with schizophrenic disorder may improve the outcomes of patients
      and their families. TRIAL REGISTRATION: IRCT Number:138809122812 N1'.

PMID- 22632136
TI  - An acute reversible experimental model of pneumonia in pigs: time-related
      histological and clinical signs changes.
AB  - The objective of this study was to evaluate the long-term survival rates,
      clinical response, and lung gross and microscopic changes in pigs treated
      intratracheally with lipopolysaccharide of Escherichia coli 0111:B4 (LPS-Ec).
      Healthy pigs were randomly allocated to three groups: (i) no-LPS-Ec (n=1), (ii)
      LPS-Ec-T1 (1 mg/mL, 10 mL/pig) (n=7), and (iii) LPS-Ec-T2 (0.5 mg/mL, 10 mL/pig)
      (n=6). Two pigs from each dose group were euthanized at 24 (n=3 for T1), 48 and
      144 h post-LPS-Ec challenge. LPS-Ec-treated animals showed macroscopic lesions in
      middle lobes of the lung. A reversible recruitment of macrophages and neutrophils
      was observed at 24, 48, and 144 h post-LPS-Ec challenge. The highest cellular
      infiltration level was observed at 24 h after challenge. The highest clinical
      scores were evident in both experimental dose levels within 3 and 5 h after LPS
      Ec administration. Administration of LPS-Ec, under the conditions evaluated, can
      be used to induce a reproducible model of acute pulmonary inflammation in pigs.

PMID- 22632137
TI  - Molecular biology of chronic myeloid leukemia.
AB  - Detailed information on the crystal structure of the pharmacologically targeted
      domains of the BCR-ABL molecule and on its intracellular signaling, which are
      potentially involved in growth, anti-apoptosis, metabolism and stemness, has made
      the study of chronic myeloid leukemia the most successful field in tumor biology.
      However, we now face the issue of drug resistance due to deregulation in the
      quality control of both DNA and protein. BCR-ABL is basically a misfolded protein
      with intrinsically disordered regions, which not only produces endoplasmic
      reticulum stress followed by unfolded protein response in some settings, but also
      conformational plasticity that may affect the structure of the whole molecule.
      The intercellular signaling derived from the leukemic cell microenvironment may
      influence the intracellular responses that take place in a manner both dependent
      on and independent of BCR-ABL tyrosine kinase activity.

PMID- 22632138
TI  - Active phytochemicals from Chinese herbs as therapeutic agents for the heart.
AB  - Naturally occurring plant alkaloids, in particular those identified from herbal
      medicines, are finding therapeutic use. Heart diseases can be well managed with
      specific formulations of herbal medicines. The combined action of multiple
      constituents of herbal medicines works with therapeutic benefits in humans. The
      established formulations of Traditional Chinese medicines show efficacy in
      treatment of diseases. However, individual herbal principles seldom show
      pharmacological activity. Nevertheless, some of the active alkaloids and
      terpenoids from medicinal herbs have been identified. The pharmacological
      activities of these herbal compounds have been studied. These active constituents
      of herbal medicine are also used in nutrient supplements, but the modes of action
      of the active component remain sketchy. The present review describes the recent
      development of those active principles from herbal medicines as cardiovascular
      agents. The study will provide insights into herbal medicines for drug
      development for the treatment of cardiovascular disease.

PMID- 22632139
TI  - Randomized controlled trial of a novel cannabis use intervention delivered by
      telephone.
AB  - AIMS: To evaluate the efficacy of a telephone-based intervention consisting of
      four sessions of motivational interviewing (MI) and cognitive behavioural therapy
      (CBT) designed to assist individuals to reduce their cannabis use and related
      problems. DESIGN: Random allocation to intervention or delayed treatment control
      with 4- and 12-week follow-up assessments. SETTING: Counsellors from the Cannabis
      Information and Helpline (CIH), an Australian reactive telephone service,
      delivered the intervention to callers seeking treatment. PARTICIPANTS: A total of
      160 participants were recruited by the CIH, with 110 participants completing the
      final follow-up assessment (69% retention). MEASUREMENTS: Cannabis use,
      dependence and related problems and other substance use were assessed at baseline
      and follow-up. FINDINGS: Intervention participants reported greater reductions in
      dependence symptoms [P < 0.001, d = 0.9 (0.5-1.3)] and related problems [P <
      0.001, d = 0.5 (0.1-0.9)] compared with control participants at both follow-up
      assessments. Compared with control, intervention participants reported greater
      confidence to reduce cannabis use at 4 weeks [P = 0.002, d = 0.5 (0.1-0.9)], and
      in turn reported a greater percentage of abstinent days at 12 weeks [P = 0.019, d
      = 0.6 (0.2-1.0)]. CONCLUSIONS: A brief course of motivational interviewing plus
      cognitive behavioural therapy delivered by telephone can help to reduce cannabis
      dependence and promote abstinence in the short term.

PMID- 22632140
TI  - A nucleotide-analogue-induced gain of function corrects the error-prone nature of
      human DNA polymerase iota.
AB  - Y-family DNA polymerases participate in replication stress and DNA damage
      tolerance mechanisms. The properties that allow these enzymes to copy past bulky
      adducts or distorted template DNA can result in a greater propensity for them to
      make mistakes. Of the four human Y-family members, human DNA polymerase iota
      (hpol iota) is the most error-prone. In the current study, we elucidate the
      molecular basis for improving the fidelity of hpol iota through use of the fixed
      conformation nucleotide North-methanocarba-2'-deoxyadenosine triphosphate (N-MC
      dATP). Three crystal structures were solved of hpol iota in complex with DNA
      containing a template 2'-deoxythymidine (dT) paired with an incoming dNTP or
      modified nucleotide triphosphate. The ternary complex of hpol iota inserting N-MC
      dATP opposite dT reveals that the adenine ring is stabilized in the anti
      orientation about the pseudo-glycosyl torsion angle, which mimics precisely the
      mutagenic arrangement of dGTP:dT normally preferred by hpol iota. The stabilized
      anti conformation occurs without notable contacts from the protein but likely
      results from constraints imposed by the bicyclo[3.1.0]hexane scaffold of the
      modified nucleotide. Unmodified dATP and South-MC-dATP each adopt syn glycosyl
      orientations to form Hoogsteen base pairs with dT. The Hoogsteen orientation
      exhibits weaker base-stacking interactions and is less catalytically favorable
      than anti N-MC-dATP. Thus, N-MC-dATP corrects the error-prone nature of hpol iota
      by preventing the Hoogsteen base-pairing mode normally observed for hpol iota
      catalyzed insertion of dATP opposite dT. These results provide a previously
      unrecognized means of altering the efficiency and the fidelity of a human
      translesion DNA polymerase.

PMID- 22632141
TI  - Preparation of multifunctional and multireactive polypeptides via methionine
      alkylation.
AB  - We report the development of a new "click"-type reaction for polypeptide
      modification based on the chemoselective alkylation of thioether groups in
      methionine residues. The controlled synthesis of methionine polymers and their
      alkylation by a broad range of functional reagents to yield stable sulfonium
      derivatives are described. These "methionine click" functionalizations are
      compatible with deprotection of other functional groups, use an inexpensive,
      natural amino acid that is readily polymerized and requires no protecting groups,
      and allow the introduction of a diverse range of functionality and reactive
      groups onto polypeptides.

PMID- 22632142
TI  - Challenges in the management of pediatric central venous access devices in the
      community.
AB  - Central venous access devices (CVADs) play an essential role in the care of
      critically ill children. Significant challenges exist for teams in managing CVADs
      particularly in a community setting. The authors aimed to assess the experience
      of general practitioners (GPs) caring for children with CVADs. From 200 CVADs
      inserted in a pediatric hospital in 2009, 50 patients were randomly selected and
      44 GPs were forwarded a questionnaire. Twenty (46%) GPs responded. The main
      reasons (n = 22) for using CVADs were medication administration (n = 11),
      nutrition (n = 6), and blood sampling (n = 5). Thirteen (65%) GPs had no
      education in CVAD management and 14 (70%) were unaware of existing guidelines.
      Those identified by GPs as having primary responsibility for care of CVADs in the
      community included hospital/pediatric teams (n = 9), parents (n = 3), GPs (n =
      2), public health nurses (n = 1), and palliative care ("home care") teams (n =
      1). The main challenges (n = 15) identified by GPs were lack of education (n =
      4), line management difficulties (n = 3), infection risk (n = 3), infrequent
      exposure to CVADs (n = 3), and poor communication (n = 1). GPs felt that these
      challenges could be addressed through: education (n = 8), increased manpower and
      community support (n = 1), and improved communication (n = 1). This study
      highlights the inconsistency and challenges for GPs surrounding CVAD use in
      children. Further education and support is necessary to assist GPs in their use
      particularly when providing end-of-life care for children in the community.

PMID- 22632143
TI  - Cell surface expression of activating receptors and co-receptors on peripheral
      blood NK cells in systemic autoimmune diseases.
AB  - OBJECTIVES: A defined role for natural killer (NK) cells and their activating
      receptors in autoimmunity has not been clearly established. The aim of this study
      was to evaluate the levels of the CD3-CD56+ NK cells and their expression of
      receptors and co-receptors in the peripheral blood of patients with systemic
      autoimmune disorders. METHODS: Thirty-four subjects with systemic sclerosis
      (SSc), 14 with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
      (AAV), 14 with systemic lupus erythematosus (SLE), and 14 healthy donors were
      studied. The activating receptors NKp46, NKp44, NKp30, NKG2D, and DNAM-1 and the
      co-receptors NTB-A and 2B4 were analysed by flow cytometry on peripheral blood NK
      cells. RESULTS: In SSc, AAV, and SLE we detected a significant decrease in the
      percentage of CD3-CD56+ NK cells compared to healthy controls. No differences in
      the expression of NKp46, NKp44, and NKp30 were identified. On the contrary, NKG2D
      and DNAM-1 expression was decreased in SLE, but not in SSc and AAV, NTB-A was
      decreased in SLE, and 2B4 in both SLE and SSc. No differences were detected
      between active and inactive SLE patients. In SSc, only patients affected by
      pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) had a
      low expression of DNAM-1, 2B4, and NKp30. CONCLUSIONS: These data demonstrate
      that patients with different systemic autoimmune diseases differ in the
      expression of activating receptors and co-receptors on CD3-CD56+ NK cells. The
      down-regulation of receptors and co-receptors in SSc with lung involvement
      suggests their possible role in this manifestation of the disease.

PMID- 22632145
TI  - A systematic review of psychological interventions for excessive alcohol
      consumption among people with psychotic disorders.
AB  - OBJECTIVE: Excessive alcohol consumption is common among people with psychotic
      disorders. While there is an extensive literature on the efficacy of
      psychological treatments for excessive drinking, few studies have examined
      interventions addressing this issue among people with psychotic disorders.
      METHOD: Systematic searches in PubMed and PsycINFO were conducted to identify
      randomized controlled trials comparing manual-guided psychological interventions
      for excessive alcohol consumption among individuals with psychotic disorders. Of
      the 429 articles identified, seven met inclusion criteria. Data were extracted
      from each study regarding study sample characteristics, design, results, clinical
      significance of alcohol consumption results, and methodological limitations.
      RESULTS: Assessment interviews, brief motivational interventions, and lengthier
      cognitive behavior therapy have been associated with reductions in alcohol
      consumption among people with psychosis. While brief interventions (i.e. 1-2
      sessions) were generally as effective as longer duration psychological
      interventions (i.e. 10 sessions) for reducing alcohol consumption, longer
      interventions provided additional benefits for depression, functioning, and other
      alcohol outcomes. CONCLUSION: Excessive alcohol consumption among people with
      psychotic disorders is responsive to psychological interventions. It is
      imperative that such approaches are integrated within standard care for people
      with psychosis.

PMID- 22632154
TI  - Kinetics of bile salt binding to liposomes revealed by carboxyfluorescein release
      and mathematical modeling.
AB  - We propose a mathematical model for the release of carboxyfluorescein from
      liposomes whose membrane permeability is modified by the binding of different
      bile salts to the leaflets of the lipid bilayer. We find that the permeability of
      the liposomal bilayer depends on the difference in the concentrations of bile
      salt in the inner and outer leaflets and is only minimally influenced by the
      total concentration of bile salt in the bilayer. Deoxycholate and cholate are
      found to behave similarly in enhancing permeability for limited times, whereas
      the novel bile salt, 12-monoketocholate, flips from the outer to inner leaflet
      slowly, thereby enhancing membrane permeability for a prolonged time.

PMID- 22632155
TI  - Fifty-six-month survival after liver transplantation in a patient with more than
      one-hundred hepatocellular carcinoma nodules.

PMID- 22632146
TI  - Spatial and temporal correlation in progressive degeneration of neurons and
      astrocytes in contusion-induced spinal cord injury.
AB  - BACKGROUND: Traumatic spinal cord injury (SCI) causes acute neuronal death
      followed by delayed secondary neuronal damage. However, little is known about how
      microenvironment regulating cells such as microglia, astrocytes, and blood
      inflammatory cells behave in early SCI states and how they contribute to delayed
      neuronal death. METHODS: We analyzed the behavior of neurons and microenvironment
      regulating cells using a contusion-induced SCI model, examining early (3-6 h) to
      late times (14 d) after the injury. RESULTS: At the penumbra region close to the
      damaged core (P1) neurons and astrocytes underwent death in a similar spatial and
      temporal pattern: both neurons and astrocytes died in the medial and ventral
      regions of the gray matter between 12 to 24 h after SCI. Furthermore, mRNA and
      protein levels of transporters of glutamate (GLT-1) and potassium (Kir4.1),
      functional markers of astrocytes, decreased at about the times that delayed
      neuronal death occurred. However, at P1 region, ramified Iba-1+ resident
      microglia died earlier (3 to 6 h) than neurons (12 to 24 h), and at the penumbra
      region farther from the damaged core (P2), neurons were healthy where microglia
      were morphologically activated. In addition, round Iba-1/CD45-double positive
      monocyte-like cells appeared after neurons had died, and expressed phagocytic
      markers, including mannose receptors, but rarely expressed proinflammatory
      mediators. CONCLUSION: Loss of astrocyte function may be more critical for
      delayed neuronal death than microglial activation and monocyte infiltration.

PMID- 22632156
TI  - Short communication: CD4 cell count increases during successful treatment of
      Graves' disease with methimazole in HIV-infected patients on antiretroviral
      therapy.
AB  - With the increased survival of HIV-infected patients receiving antiretroviral
      therapy (ART), unexpected complications due to the untoward effect of
      antiretroviral agents or immunologic changes have been observed. Here, we report
      two cases of Graves' disease (GD) presenting with classic symptoms of
      hyperthyroidism occurring 44 and 47 months after ART initiation. Both patients
      had severe immune suppression prior to ART initiation (CD4 cell count<=50
      cells/MUL), with an increase on CD4 cell count to 354 and 329 cells/MUL,
      respectively, at the time of GD diagnosis. Administration of methimazole (MMI)
      resulted in dramatic improvements in symptoms and thyroid function. In addition,
      CD4 cell count unexpectedly increased to >500 cells/MUL within three months on
      MMI. Hyperthyroidism caused by GD has been increasingly reported following the
      initiation of ART and may be related to immune reconstitution. The mechanisms
      underlying the increases in CD4 cell count after successful treatment of GD with
      MMI require further investigation, but may be due to improved immune recovery
      with the correction of hyperthyroidism or a specific effect of MMI on immune
      function.

PMID- 22632157
TI  - Family perspectives in lynch syndrome becoming a family at risk, patterns of
      communication and influence on relations.
AB  - BACKGROUND: A growing number of individuals are diagnosed with hereditary cancer.
      Though increased levels of anxiety and depression have been demonstrated around
      the time of genetic counselling, most individuals handle life at increased risk
      well. Data have, however, been collected on individual basis, which led us to
      focus on family perspectives of hereditary cancer. METHODS: Lynch syndrome
      represents a major type of hereditary colorectal and gynaecological cancer. We
      preformed open-ended interviews with 27 informants from 9 Lynch syndrome
      families. Inductive content analysis revealed three major themes: transition to a
      risk family, patterns of communication and influence on family relations and
      individual roles. RESULTS: Family members described how learning about Lynch
      syndrome shifted focus from daily issues to concerns about cancer. Changes in
      communication related to difficulties in talking to children about heredity and
      informing new family members and distant relatives about an increased risk of
      cancer. Influence on relations was exemplified by family members taking on
      different roles, e.g. females often being responsible for coordinating
      information about heredity and providing support. Families in which members had
      experienced cancer at young age typically informed children soon after learning
      about heredity and at young age, whereas families with experience of cancer at
      higher age postponed information and thereby also genetic counselling.
      CONCLUSIONS: Three major family perspectives are described in Lynch syndrome
      families; becoming a risk family, patterns of communication and influence on
      family relations. Since these issues are central, our findings suggests that such
      family perspectives should be considered during genetic counselling in order to
      contribute to information spread, help family members cope with the increased
      risk, and motivate family members at risk to undergo surveillance.

PMID- 22632158
TI  - Layer-by-layer graphene/TCNQ stacked films as conducting anodes for organic solar
      cells.
AB  - Large-area graphene grown by chemical vapor deposition (CVD) is a promising
      candidate for transparent conducting electrode applications in flexible
      optoelectronic devices such as light-emitting diodes or organic solar cells.
      However, the power conversion efficiency (PCE) of the polymer photovoltaic
      devices using a pristine CVD graphene anode is still not appealing due to its
      much lower conductivity than that of conventional indium tin oxide. We report a
      layer-by-layer molecular doping process on graphene for forming sandwiched
      graphene/tetracyanoquinodimethane (TCNQ)/graphene stacked films for polymer solar
      cell anodes, where the TCNQ molecules (as p-dopants) were securely embedded
      between two graphene layers. Poly(3-hexylthiophene)/phenyl-C61-butyric acid
      methyl ester (P3HT/PCBM) bulk heterojunction polymer solar cells based on these
      multilayered graphene/TCNQ anodes are fabricated and characterized. The P3HT/PCBM
      device with an anode structure composed of two TCNQ layers sandwiched by three
      CVD graphene layers shows optimum PCE (~2.58%), which makes the proposed anode
      film quite attractive for next-generation flexible devices demanding high
      conductivity and transparency.

PMID- 22632159
TI  - Total anomalous systemic venous drainage in left heterotaxy syndrome.
AB  - Total anomalous systemic venous drainage is an extremely rare congenital heart
      defect. In this study we describe an 11-year-old girl who presented with a
      history of fatigue and central cyanosis that she had had since early childhood
      with unremarkable precordial examination results. Investigations revealed left
      heterotaxy with all systemic venous drainage to the left-sided atrium with non
      compaction of the left ventricle.

PMID- 22632160
TI  - Mechanisms and monitoring of bypassing agent therapy.
AB  - Understanding the mechanism of action of normal hemostasis and how the bypassing
      agents recombinant activated factor VII (rFVIIa; NovoSeven) and plasma-derived
      activated prothrombin complex concentrate (Factor Eight Inhibitor Bypassing Agent
      [FEIBA]) control abnormal bleeding is imperative for healthcare professionals who
      treat patients with hemophilia and other bleeding disorders. A cell-based model
      has improved our understanding of in vivo mechanisms of hemostasis and the basis
      of the bleeding tendency in hemophilia. Bypassing agents do not restore the
      normal pathways of hemostasis in hemophilia, but rather boost thrombin generation
      in spite of a lack of platelet surface FVIIIa-FIXa ('tenase') activity. Thus, the
      common clinical laboratory coagulation assays do not reflect the clinically
      relevant hemostatic activity of bypassing agents, and no validated assay is
      available with which to measure the in vivo efficacy of these agents or predict
      individual patient responses to treatment. Global hemostasis assays measuring
      overall coagulation capacity have potential for assessment of the effects of
      bypassing agents. This review will focus on the mechanisms of clotting and their
      relationship to understanding the mechanisms of action of the bypassing agents in
      vivo and the methodologies that are emerging to monitor the clinical efficacy of
      bypassing agent therapy.

PMID- 22632161
TI  - Selective metal cation capture by soft anionic metal-organic frameworks via
      drastic single-crystal-to-single-crystal transformations.
AB  - Flexible anionic metal-organic frameworks (MOFs) are transformed into neutral
      heterobimetallic systems via single-crystal-to-single-crystal processes invoked
      by cation insertion. These transformations are directed by cooperative bond
      breakage and formation, resulting in expansion or contraction of the 3D framework
      by up to 33% due to the flexible nature of the organic linker. These MOFs
      displays highly selective uptake of divalent transition-metal cations (e.g.,
      Co(2+) and Ni(2+)) over alkali-metal cations (Li(+) and Na(+)).

PMID- 22632162
TI  - The global gene-expression profiles of U-937 human macrophages treated with Tat
      peptide and Tat-FITC conjugate.
AB  - There is increased interest in using cell penetrating peptides such as HIV Tat
      derived peptide (Tat) to deliver biologically active cargo to cells. However,
      little is known about the precise molecular mechanism in cells after the uptake
      of Tat and after it conjugates with the cargo. Using high-density microarray
      analysis, we evaluated the alteration of whole genomic responses in U-937
      macrophages that had been treated with Tat and Tat-fluorescein-5-isothiocynate
      (FITC), which served as model cargo, and then incubated for 24 h. Sixteen genes
      were upregulated and 28 downregulated in Tat-treated cells. After FITC had
      conjugated to Tat, 13 genes were upregulated and 23 downregulated. Ten
      upregulated and 13 downregulated genes were overlapped by both Tat and Tat-FITC.
      The molecular functions of regulated genes affected by Tat and Tat-FITC are
      described. A real-time quantitative reverse transcriptase-polymerase chain
      reaction was used to confirm three regulated genes (IFNAR2, CASP8, and CRLF1)
      affected by both Tat and Tat-FITC. We demonstrated that regulating the three
      genes was time-dependent and that CASP8 is also kinetically regulated in HeLa
      cells. Understanding the influences and consequences of Tat (Tat-cargo)-induced
      gene changes should help us design and develop efficient and safe delivery
      systems into target cells.

PMID- 22632163
TI  - A time-lapse approach to examine chromium and nickel effects on wound healing in
      vitro.
AB  - Chromium and nickel cause allergic contact dermatitis, a common biological skin
      response to sensitizing agents. This study used a conventional in vitro wounding
      model to study the impact of sensitizing agents on the innate immune response of
      human keratinocytes. Experiments were designed to evaluate the involvement of
      specific Toll-like receptors and metalloproteinases as effectors molecules
      downstream, at a molecular level. Further, keratinocytes were co-cultured with
      monocytes (THP-1 cells) to reproduce an inductive stimulus on monocytes made by
      metals. Human keratinocytes (HaCat) were grown on plates covered with collagen
      type I, chemically treated, and then mechanically injured with a sterile pipette
      tip. Restoration of the monolayer integrity was monitored by time-lapse video
      microscopy. Effector gene expression was evaluated by real-time PCR. The presence
      of chromium significantly dropped the rate of wound closure, while nickel-induced
      hyper-proliferation ended in an acceleration of the healing process, an event
      that does not occur in vivo. This latter outcome led to considering nickel as an
      unsuitable example for use in the experimental model. Focusing solely on the
      chromium aspect of this study, RNA profiles of selected molecular markers were
      generated to ascertain if the detrimental stimulus from chromium was eliminated
      or persisted both in keratinocytes alone and/or during co-cultures of
      keratinocytes and monocytes. Monocytes accelerated the process of wound repair.
      This in vitro experimental model highlighted the involvement of innate immunity
      in response to chromium and might be useful for test molecules of therapeutic
      interest for the treatment of skin lesions. However, the experience with nickel
      reveals that there are limitations to the utility of this wound model system
      after all.

PMID- 22632165
TI  - Function of defensive volatiles in pedunculate oak (Quercus robur) is tricked by
      the moth Tortrix viridana.
AB  - The indirect defences of plants are comprised of herbivore-induced plant
      volatiles (HIPVs) that among other things attract the natural enemies of insects.
      However, the actual extent of the benefits of HIPV emissions in complex co
      evolved plant-herbivore systems is only poorly understood. The observation that a
      few Quercus robur L. trees constantly tolerated (T-oaks) infestation by a major
      pest of oaks (Tortrix viridana L.), compared with heavily defoliated trees
      (susceptible: S-oaks), lead us to a combined biochemical and behavioural study.
      We used these evidently different phenotypes to analyse whether the resistance of
      T-oaks to the herbivore was dependent on the amount and scent of HIPVs and/or
      differences in non-volatile polyphenolic leaf constituents (as quercetin-,
      kaempferol- and flavonol glycosides). In addition to non-volatile metabolic
      differences, typically defensive HIPV emissions differed between S-oaks and T
      oaks. Female moths were attracted by the blend of HIPVs from S-oaks, showing
      significantly higher amounts of (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) and (E)
      beta-ocimene and avoid T-oaks with relative high fraction of the sesquiterpenes
      alpha-farnesene and germacrene D. Hence, the strategy of T-oaks exhibiting
      directly herbivore-repellent HIPV emissions instead of high emissions of predator
      attracting HIPVs of the S-oaks appears to be the better mechanism for avoiding
      defoliation.

PMID- 22632164
TI  - Enhancement of vitamin D metabolites in the eye following vitamin D3
      supplementation and UV-B irradiation.
AB  - PURPOSE: This study was designed to measure vitamin D metabolites in the aqueous
      and vitreous humor and in tear fluid, and to determine if dietary vitamin D3
      supplementation affects these levels. We also determined if the corneal
      epithelium can synthesize vitamin D following UV-B exposure. METHODS: Rabbits
      were fed a control or vitamin D3 supplemented diet. Pilocarpine-stimulated tear
      fluid was collected and aqueous and vitreous humor were drawn from enucleated
      eyes. Plasma vitamin D was also measured. To test for epithelial vitamin D
      synthesis, a human corneal limbal epithelial cell line was irradiated with two
      doses of UV-B (10 and 20 mJ/cm(2)/day for 3 days) and vitamin D was measured in
      control or 7-dehydrocholesterol treated culture medium. Measurements were made
      using mass spectroscopy. RESULTS: 25(OH)-vitamin D3 and 24,25(OH)(2)-vitamin D3
      increased significantly following D3 supplementation in all samples except
      vitreous humor. Tear fluid and aqueous humor had small but detectable 1,25(OH)(2)
      vitamin D3 levels. Vitamin D2 metabolites were observed in all samples. Vitamin
      D3 levels were below the detection limit for all samples. Minimal vitamin D3
      metabolites were observed in control and UV-B-irradiated epithelial culture
      medium except following 7-dehydrocholesterol treatment, which resulted in a UV-B
      dose dependent increase in vitamin D3, 25(OH)-vitamin D3 and 24,25(OH)(2)-vitamin
      D3. CONCLUSIONS: There are measurable concentrations of vitamin D metabolites in
      tear fluid and aqueous and vitreous humor, and oral vitamin D supplementation
      affects vitamin D metabolite concentrations in the anterior segment of the eye.
      In addition, the UV exposure results lead us to conclude that corneal epithelial
      cells are likely capable of synthesizing vitamin D3 metabolites in the presence
      of 7-dehydrocholesterol following UV-B exposure.

PMID- 22632166
TI  - Zinc finger E-box binding homeobox 1 promotes invasion and bone metastasis of
      small cell lung cancer in vitro and in vivo.
AB  - Bone is one of the most frequent targets of small cell lung cancer (SCLC)
      metastasis and is closely associated with a poor prognosis, but the specific
      cellular gene alterations responsible for SCLC with bone metastasis are unclear.
      Zinc finger E-box binding homeobox 1 (ZEB1) as an E-box transcriptional repressor
      has been suggested that an important inducer of the epithelial-mesenchymal
      transition (EMT) and a promoter of tumor metastasis in colon, breast and lung
      cancers. However, the relationship between ZEB1 and SCLC with bone metastasis is
      unclear. In this study, ZEB1 was found to be highly expressed in bone-metastatic
      SCLC tissues and cell lines as compared with those that were non-metastatic (P <
      0.05). Using a lentivirus RNA interference technique to knockdown ZEB1 expression
      in bone-metastatic SCLC cells (SBC-5 cell line), we found that ZEB1 siRNA could
      inhibit the invasive and migratory ability and decrease parathyroid hormone
      related protein expression, as determined by invasion assays and enzyme-linked
      immunosorbent assays. Besides, ZEB1 siRNA significantly inhibited the bone
      metastasis of SBC-5 cells in vivo. Furthermore, overexpression of ZEB1 in SBC-3
      cells, which demonstrate promoted bone-metastatic potential, dramatically
      promoted their invasive and migratory ability and parathyroid hormone-related
      protein expression as well as increased the number and sites of bone metastases
      in vivo compare to the control group. We also found that SBC-3 cells underwent
      EMT, as indicated by decreased epithelial markers and increased mesenchymal
      marker expression. Taken together, these results indicate that ZEB1 promoted the
      invasive ability and bone metastasis of SCLC cells, and that this was partially
      mediated via the EMT pathway.

PMID- 22632167
TI  - Emotional but not physical maltreatment is independently related to
      psychopathology in subjects with various degrees of social anxiety: a web-based
      internet survey.
AB  - BACKGROUND: Previous studies reported that social phobia is associated with a
      history of child maltreatment. However, most of these studies focused on physical
      and sexual maltreatment whilst little is known about the specific impact of
      emotional abuse and neglect on social anxiety. We examined the association
      between emotional maltreatment, including parental emotional maltreatment as well
      as emotional peer victimization, and social anxiety symptoms in subjects with
      various degrees of social anxiety. METHODS: The study was conducted as a web
      based Internet survey of participants (N = 995) who had social anxiety symptoms
      falling within the high range, and including many respondents who had scores in
      the clinical range. The assessment included measures of child maltreatment,
      emotional peer victimization, social anxiety symptoms and general
      psychopathology. RESULTS: Regression and mediation analyses revealed that
      parental emotional maltreatment and emotional peer victimization were
      independently related to social anxiety and mediated the impact of physical and
      sexual maltreatment. Subjects with a history of childhood emotional maltreatment
      showed higher rates of psychopathology than subjects with a history of physical
      maltreatment. CONCLUSIONS: Although our findings are limited by the use of an
      Internet survey and retrospective self-report measures, data indicated that
      social anxiety symptoms are mainly predicted by emotional rather than physical or
      sexual types of victimization.

PMID- 22632168
TI  - Pediatric Hodgkin lymphoma: are we over-scanning our patients?
AB  - Despite the favorable outcome of most pediatric patients with Hodgkin lymphoma
      (HL), there is rising concern about risks of carcinogenesis from both diagnostic
      and therapeutic radiation exposure for patients treated on study protocols.
      Although previous studies have investigated radiation exposure during treatment,
      radiation from post-treatment surveillance imaging may also increase the
      likelihood of secondary malignancies. All diagnostic imaging examinations
      involving ionizing radiation exposure performed for surveillance following
      completion of therapy were recorded for 99 consecutive pediatric patients
      diagnosed with HL from 2000 to 2010. Cumulative radiation dosage from these
      examinations and the frequency of relapse detection by these examinations were
      recorded. In the first 2 years following completion of therapy, patients in
      remission received a median of 11 examinations (range 0-26). Only 13 of 99
      patients relapsed, 11 within 5 months of treatment completion. No relapse was
      detected by 1- or 2-view chest radiographs (n = 38 and 296, respectively),
      abdomen/pelvis computed tomography (CT) scans (n = 211), or positron emission
      tomography (PET) scans alone (n = 11). However, 10/391 (2.6%) of chest CT scans,
      4/364 (1.1%) of neck CT scans, and 3/47 (6.4%) of PET/CT scans detected relapsed
      disease. Thus, only 17 scans (1.3%) detected relapse in a total of 1358 scans.
      Mean radiation dosages were 31.97 mSv for Stage 1, 37.76 mSv for Stage 2, 48.08
      mSv for Stage 3, and 51.35 mSv for Stage 4 HL. Approximately 1% of surveillance
      imaging examinations identified relapsed disease. Given the very low rate of
      relapse detection by surveillance imaging stipulated by current protocols for
      pediatric HL patients, the financial burden of the tests themselves, the high
      cure rate, and risks of second malignancy from ionizing radiation exposure,
      modification of the surveillance strategy is recommended.

PMID- 22632170
TI  - The complete mitochondrial genome sequence of Eimeria mitis (Apicomplexa:
      Coccidia).
AB  - In this study the complete mitochondrial DNA (mtDNA) sequence of Eimeria mitis
      was sequenced, and its gene contents and genome organizations were compared with
      that of other Eimeria spp. The complete mt genome sequence of E. mitis is 6407 bp
      in size. It consists of 3 protein-coding genes (cox1, cox3, and cytb), 12 gene
      fragments for the large subunit (LSU) rRNA, and 7 gene fragments for the small
      subunit (SSU) rRNA, but no transfer RNA genes, similar to that of Eimeria spp.
      The putative direction of translation for three genes (cox1, cox3, and cytb) was
      the same as those of six other Eimeria spp. The A+T content of the E. mitis mt
      genome was 67.30%. The E. mitis mt genome sequence provides novel mtDNA marker
      for studying the molecular epidemiology and population genetics of E. mitis and
      has implications for the molecular diagnosis of chicken coccidiosis caused by E.
      mitis.

PMID- 22632169
TI  - The changing gender gap in substance use disorder: a total population-based study
      of psychiatric in-patients.
AB  - AIMS: To study changes over a 25-year period in the gender gap in discharge
      diagnoses of alcohol use disorder (AUD) and other substance use disorder (SUD) in
      psychiatric in-patients. DESIGN, SETTING AND PARTICIPANTS:  A register-based
      study of all admissions to psychiatric hospitals in Iceland between January 1983
      and December 2007. MEASUREMENTS: Annual rate of admissions to psychiatric
      hospitals, adjusted for changes in the size of the population. Furthermore,
      gender-specific analysis of changes in discharge diagnoses of AUD solely and
      other SUD (including AUD with other SUDs). FINDINGS: Of all psychiatric
      admissions, the proportion of any SUD admissions increased considerably during
      the study period. This increase was most pronounced in SUDs other than solely
      AUD. AUD increased for women and decreased for men. The male to female ratio of
      AUD alone decreased from 4.2 to 1.5 (P < 0.001). There was no significant change
      in the gender gap for other SUDs (P = 0.96). CONCLUSIONS: There has been a marked
      convergence of the gender gap in discharge diagnosis of alcohol use disorder
      among psychiatric in-patients in Iceland over the last decades. For other
      substance use disorders, the change was not as pronounced. Our results emphasize
      the importance of monitoring changes in substance use disorder diagnosis as this
      may uncover different treatment needs in this group of vulnerable individuals.

PMID- 22632171
TI  - An evaluation of training in motivational interviewing for nurses in child health
      services.
AB  - BACKGROUND: Acquiring proficiency in motivational interviewing (MI) may be more
      difficult than generally believed, and training research suggests that the
      standard one-time workshop format may be insufficient. Although nurses represent
      one of the professions that have received most training in MI, training in this
      group has rarely been systematically evaluated using objective behavioral
      measures. AIMS: To evaluate an enhanced MI training program, comprising a 3.5-day
      workshop, systematic feedback on MI performance, and four sessions of supervision
      on practice samples. METHODS: Nurses (n = 36) in Swedish child health services
      were trained in MI. Skillfulness in MI was assessed using the Motivational
      Interviewing Treatment Integrity (MITI) Code. Effects of training were compared
      to beginning proficiency thresholds. RESULTS: Participants did not reach
      beginning proficiency thresholds on any of the indicators of proficiency and
      effect sizes were small. CONCLUSIONS: The present study adds to a growing body of
      literature suggesting that the current standard MI training format may not
      provide practitioners with enough skillfulness. Moreover, the results indicate
      that even enhanced training, including systematic feedback and supervision, may
      not be sufficient. Suggestions for improved MI training are made.

PMID- 22632172
TI  - The natural course of social anxiety disorder among adolescents and young adults.
AB  - OBJECTIVE: To examine the natural course of social anxiety disorder (SAD) in the
      community and to explore predictors for adverse long-term outcomes. METHOD: A
      community sample of N = 3021 subjects aged 14-24 was followed-up over 10 years
      using the DSM-IV/M-CIDI. Persistence of SAD is based on a composite score
      reflecting the proportion of years affected since onset. Diagnostic stability is
      the proportion of SAD subjects still affected at follow-up. RESULTS: SAD reveals
      considerable persistence with more than half of the years observed since onset
      spent with symptoms. 56.7% of SAD cases revealed stability with at least
      symptomatic expressions at follow-up; 15.5% met SAD threshold criteria again.
      15.1% were completely remitted (no SAD symptoms and no other mental disorders
      during follow-up). Several clinical features (early onset, generalized subtype,
      more anxiety cognitions, severe avoidance and impairment, co-occurring panic) and
      vulnerability characteristics (parental SAD and depression, behavioural
      inhibition, harm avoidance) predicted higher SAD persistence and - less
      impressively - diagnostic stability. CONCLUSION: A persistent course with a
      considerable degree of fluctuations in symptom severity is characteristic for
      SAD. Both consistently meeting full threshold diagnostic criteria and complete
      remissions are rare. Vulnerability and clinical severity indicators predict poor
      prognosis and might be helpful markers for intervention needs.

PMID- 22632173
TI  - Multivariate analysis of C-5 palsy incidence after cervical posterior fusion with
      instrumentation.
AB  - OBJECT: Postoperative C-5 palsy is a significant complication resulting from
      cervical decompression procedures. Moreover, when cervical degenerative diseases
      are treated with a combination of decompression and posterior instrumented
      fusion, patients are at increased risk for C-5 palsy. However, the clinical and
      radiological features of this condition remain unclear. Therefore, the purpose of
      this study was to clarify the risk factors for developing postoperative C-5
      palsy. METHODS: Eighty-four patients (mean age 60.1 years) who had undergone
      posterior instrumented fusion using cervical pedicle screws to treat nontraumatic
      lesions were independently reviewed. The authors analyzed the medical records of
      some of these patients who developed postoperative C-5 palsy, paying particular
      attention to their plain radiographs, MRI studies, and CT scans. Risk factors for
      postoperative C-5 palsy were assessed using multivariate logistic regression
      analysis. The cutoff values for the pre- and postoperative width of the
      intervertebral foramen (C4-5) were determined by receiver operating
      characteristic curve analysis. RESULTS: Ten (11.9%) of 84 patients developed
      postoperative C-5 palsy. Seven patients recovered fully from the neurological
      complications. The pre- and postoperative C4-5 angles showed significant kyphosis
      in the C-5 palsy group. The pre- and postoperative diameters of the C4-5 foramen
      on the palsy side were significantly smaller than those on the opposite side in
      the C-5 palsy group and those bilaterally in the non-C5 palsy group. Risk factors
      identified by multivariate logistic regression analysis were as follows: 1)
      ossification of the posterior longitudinal ligament (relative risk [RR] 7.22 [95%
      CI 1.03-50.55]); 2) posterior shift of the spinal cord (C4-5) (RR 1.73 [95% CI
      1.00-2.98]); and 3) postoperative width of the C-5 intervertebral foramen (RR
      0.33 [95% CI 0.14-0.79]). The cutoff values of the pre- and postoperative widths
      of the C-5 intervertebral foramen for C-5 palsy were 2.2 and 2.3 mm,
      respectively. CONCLUSIONS: Patients with preoperative foraminal stenosis,
      posterior shift of the spinal cord, and additional iatrogenic foraminal stenosis
      due to cervical alignment correction were more likely to develop postoperative C
      5 palsy after posterior instrumentation with fusion. Prophylactic foraminotomy at
      C4-5 might be useful when preoperative foraminal stenosis is present on CT.
      Furthermore, it might be useful for treating postoperative C-5 palsy. To prevent
      excessive posterior shift of the spinal cord, the authors recommend that
      appropriate kyphosis reduction should be considered carefully.

PMID- 22632174
TI  - A 3D environment for anulus fibrosus regeneration.
AB  - OBJECT: Biological repair strategies for the treatment of degenerated
      intervertebral discs are of growing interest. In addition to the development of
      nucleus pulposus implants to restore disc height and relieve pain, there is
      growing demand for an appropriate method for reconstructing the anulus fibrosus
      (AF). The aim of this pilot study was to evaluate the applicability of a
      resorbable 3D polymer of pure polyglycolic acid (PGA) combined with hyaluronan
      for the use in cell-free and cell-based regeneration and repair of the AF.
      METHODS: Adult human AF cells were expanded in vitro using human serum and
      rearranged three dimensionally in hyaluronan-PGA scaffolds that were stabilized
      with fibrin for in vitro analyses. The capacity of dedifferentiated AF cells to
      redifferentiate was evaluated after 2 weeks of culture, using propidium
      iodide/fluorescein diacetate staining, gene expression analysis of typical marker
      genes, and histological staining of proteoglycans. RESULTS: The propidium
      iodide/fluorescein diacetate staining demonstrated that vital human AF cells were
      evenly distributed within the construct. The induction of typical AF marker genes
      such as collagen Types I-III indicated the initiation of AF redifferentiation by
      3D assembly in hyaluronan-PGA. Histological analysis of the constructs showed
      initial formation of an AF-like matrix comprising proteoglycans. CONCLUSIONS: The
      results suggest that the 3D arrangement of human AF cells in resorbable
      hyaluronan-PGA scaffolds cultured in the presence of human serum is an excellent
      system for AF cell redifferentiation.

PMID- 22632175
TI  - Minimally invasive tubular retractor system for adequate exposure during surgical
      obliteration of spinal dural arteriovenous fistulas with the aid of indocyanine
      green intraoperative angiography.
AB  - Effective surgical obliteration of spinal dural arteriovenous fistulas (DAVFs)
      traditionally requires laminectomy or hemilaminectomy to allow intradural
      exposure and occlusion of the draining vein. The authors present successful
      treatment of a spinal DAVF by using a tubular retractor system to provide
      minimally invasive exposure at the L5-S1 level adequate for both microsurgical
      treatment and intraoperative indocyanine green angiography.

PMID- 22632176
TI  - Editorial: C-5 palsy and foraminal stenosis.

PMID- 22632177
TI  - Structural and thermal analysis of lipid vesicles encapsulating hydrophobic gold
      nanoparticles.
AB  - The structure and stability of hybrid lipid vesicles containing bilayer
      encapsulated hydrophobic nanoparticles is dependent upon lipid phase behavior. By
      embedding stearylamine-stabilized gold nanoparticles in
      dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol vesicles, we show
      that encapsulation at lipid to nanoparticle ratios from 10,000:1 to 5000:1 leads
      to bilayer thickening and hydrophobic mismatch, favoring nanoparticle inclusion
      in gel phase vesicles. High loadings lead to large increases in the gel to fluid
      melting temperature upon heating and significant hysteresis on cooling, which
      cannot be attributed solely to excess free ligand. This behavior is due to a
      cooperative effect of excess free SA ligand and nanoparticle embedment.
      Nanoparticle clustering was observed during lipid melting and could be reversed
      upon lipid freezing owing to lateral capillary forces within the bilayer. The
      impact of nanoparticle embedment on vesicle structure and properties at such low
      concentrations is reminiscent of hydrophobic proteins, suggesting that the
      underlying lipid biophysics between proteins and nanoparticle are similar and may
      provide a predictive design tool for therapeutic applications.

PMID- 22632178
TI  - The relationship between value incongruence and individual and organizational
      well-being outcomes: an exploratory study among Catalan nurses.
AB  - AIMS: To report a correlational study of the relations of value incongruence to
      the individual and organizational well-being variables of self-rated health,
      turnover intention, and accident propensity, as mediated by burnout. BACKGROUND:
      Previous literature found that value incongruence may lessen individual and
      organizational well-being through the psychological mechanism of burnout.
      Empirical investigation is needed to validate these claims. DESIGN: A cross
      sectional between-cases correlational design was used. METHODS: A survey was
      conducted in one of the largest university hospitals in a large metropolitan city
      in Spain in the spring of 2009, using a cross-sectional design. A total of 234
      nurses participated in the study. Stepwise regression was used to test the direct
      and mediation relationships. RESULTS: Hypotheses were confirmed for certain axes
      of values and outcome variables. In particular, Economical and Ethical value
      incongruence were found to be correlated with burnout. Economical, Ethical, and
      Emotional value incongruence were found to be correlated with turnover intention.
      Ethical and Emotional value incongruence were found to be correlated with
      accident propensity. Burnout partially mediated the relationship between
      Economical and Ethical value incongruence and turnover intention and fully
      mediated the relationship between Ethical value incongruence and accident
      propensity. CONCLUSION: The purported mediation of burnout on the relationship
      between value incongruence and individual and organizational well-being outcomes
      is valid on certain axes of values and outcome variables. This calls for caution
      when discussing value incongruence in organizations. Instead of advocating broad
      organizational culture congruence, we should target specific axes of values.

PMID- 22632179
TI  - The rise and fall of bioterrorism research.

PMID- 22632180
TI  - Pharmaceutical quality: an urgent and unresolved issue.

PMID- 22632182
TI  - HIV laboratory monitoring for effective ART in Africa.

PMID- 22632183
TI  - Preventing AIDS deaths: cryptococcal antigen screening and treatment.

PMID- 22632184
TI  - Poliovirus eradication.

PMID- 22632185
TI  - Poliovirus eradication.

PMID- 22632186
TI  - Community-acquired bacterial bloodstream infections in developing countries in
      south and southeast Asia: a systematic review.
AB  - Information about community-acquired bacteraemia in developing countries in south
      and southeast Asia is scarce. We aimed to establish the case fraction of
      bacteraemia in febrile patients admitted to hospital. We searched four databases
      and identified studies of south and southeast Asia published between 1990 and
      2010 that prospectively assessed patients admitted to hospital and from whom a
      blood culture was taken. We reviewed 17 eligible studies describing 40,644
      patients. Pathogenic organisms were isolated from 3506 patients (9%; range 1
      51%); 1784 (12%) of 14,386 adults and 1722 (7%) of 26,258 children. Salmonella
      enterica serotype Typhi was the most common bacterial pathogen, accounting for
      532 of 1798 (30%) isolates in adults and 432 of 1723 (25%) in children. Other
      commonly isolated organisms in adults were Staphylococcus aureus, Escherichia
      coli, and other gram-negative organisms, and in children were Streptococcus
      pneumoniae and Haemophilus influenzae. A substantial case fraction of bacteraemia
      occurs in patients admitted to hospital with fever in this region. Management
      could be improved if diagnostic microbiology facilities were more widely
      available. The prevailing organisms causing bacteraemia and their susceptibility
      patterns could inform empirical treatment regimens and prevention strategies.

PMID- 22632187
TI  - Poor-quality antimalarial drugs in southeast Asia and sub-Saharan Africa.
AB  - Poor-quality antimalarial drugs lead to drug resistance and inadequate treatment,
      which pose an urgent threat to vulnerable populations and jeopardise progress and
      investments in combating malaria. Emergence of artemisinin resistance or
      tolerance in Plasmodium falciparum on the Thailand-Cambodia border makes
      protection of the effectiveness of the drug supply imperative. We reviewed
      published and unpublished studies reporting chemical analyses and assessments of
      packaging of antimalarial drugs. Of 1437 samples of drugs in five classes from
      seven countries in southeast Asia, 497 (35%) failed chemical analysis, 423 (46%)
      of 919 failed packaging analysis, and 450 (36%) of 1260 were classified as
      falsified. In 21 surveys of drugs from six classes from 21 countries in sub
      Saharan Africa, 796 (35%) of 2297 failed chemical analysis, 28 (36%) of 77 failed
      packaging analysis, and 79 (20%) of 389 were classified as falsified. Data were
      insufficient to identify the frequency of substandard (products resulting from
      poor manufacturing) antimalarial drugs, and packaging analysis data were scarce.
      Concurrent interventions and a multifaceted approach are needed to define and
      eliminate criminal production, distribution, and poor manufacturing of
      antimalarial drugs. Empowering of national medicine regulatory authorities to
      protect the global drug supply is more important than ever.

PMID- 22632256
TI  - The impact of impaired kidney function and HIV infection on the risk of anemia.
AB  - Chronic kidney disease and HIV infection both independently increase the risk of
      anemia. It is not known if individuals with both HIV infection and kidney
      dysfunction are at greater than expected risk of anemia resulting from the
      combined effect of these factors. Men from the Multicenter AIDS Cohort Study with
      AIDS-free time after 1996 were included in the analysis if they had an initial
      hemoglobin value greater than 13 g/dl and available serum creatinine measurements
      for the estimation of glomerular filtration rate. Hemoglobin data were fit
      parametrically using a linear mixed effects model and effects of medication use
      on hemoglobin levels were removed using censoring methods. The effect of both HIV
      infection and glomerular filtration rate less than 60 ml/min/1.73 m(2) on the
      mean hemoglobin value was assessed. The risk of having anemia (hemoglobin level
      falling below 13 g/dl) was estimated. There were 862 HIV-infected and 1,214 HIV
      uninfected men who contributed to the analysis. Hemoglobin values across all
      17,341 person-visits, adjusting for age, were generally lower in HIV-infected
      AIDS-free men with impaired kidney function by -0.22 g/dl (95% CI: -0.42, -0.03)
      compared to men with either HIV infection or impaired kidney function, but not
      both. HIV-infected AIDS-free men with impaired kidney function have a higher risk
      of anemia by 1.2% compared to HIV-uninfected men with normal kidney function.
      Comorbid conditions and medication use did not explain this increase in risk. HIV
      infection and impaired kidney function have a combined impact on lowering
      hemoglobin levels, resulting in a higher risk of anemia.

PMID- 22632258
TI  - Can mucosal adjuvants contribute to the induction of immunological memory induced
      via unconjugated T-cell-independent antigens?
AB  - Vaccination remains the most cost-effective method for preventing infectious
      diseases. Key to vaccine design is the development of immunological memory, which
      is an essential property of the adaptive immune system. Bacterial polysaccharide
      conjugate vaccines are the gold standard currently used to confer protection of
      the host by inducing humoral immune responses against T-cell-independent
      antigens. Conjugate vaccines are effective, but we propose that local mucosal
      immune responses are likely to also play an important role in inducing immunity,
      and they have been less explored than systemic and adaptive immune responses.
      Adjuvants have been used to improve the immune response to vaccine antigens,
      however, no mucosal adjuvant has been licensed for human use. Here we describe
      the recent progress in the use of mucosal adjuvants to achieve significant immune
      responses against T-cell-independent antigens. We also introduce the idea that
      studying the mechanisms that induce cell sub-populations with strong
      immunological memory may facilitate the design of novel vaccine formulations, in
      particular in cases of B-cell unresponsiveness to thymus-independent stimuli.

PMID- 22632259
TI  - Are postoperative complications more common following colon and rectal surgery in
      patients with chronic kidney disease?
AB  - AIM: According to National Kidney Foundation guidelines, early stages of chronic
      kidney disease (CKD) can be detected through the estimated glomerular filtration
      rate (eGFR). We assessed complications following colorectal surgery (CRS) in
      patients with CKD Stages 3 and 4, as defined by the eGFR. METHOD: Patients with
      CKD were identified within our database. Patients with an eGFR of 15-59 ml/min
      (CKD Stages 3 and 4) formed the CKD group and were compared with American Society
      of Anesthesiology (ASA) score-matched controls with an eGFR of >= 60 ml/min.
      Assessments included demographics, comorbidity, ASA score, operative details and
      30-day postoperative outcome. RESULTS: Seventy patients in the CKD group were
      matched with 70 controls. ASA scores and length of stay did not differ
      significantly between the groups. CKD patients were older (mean age 76.5 years vs
      71.1 years; P < 0.001) and had a lower mean body mass index (24.3 vs 28.2; P <
      0.001) compared with controls. Compared with the CKD group, the mean operation
      time was longer in the control group (181.5 min vs 151.6 min; P = 0.02) and the
      estimated blood loss was greater (232 ml vs 165 ml; P = 0.004). Postoperative
      infection was more common in the CKD group (60%vs 40%; P = 0.01). There were no
      significant differences in reoperation rates, 30-day readmissions or the
      incidence of acute renal failure (ARF). CONCLUSION: Patients with CKD Stages 3
      and 4 had a higher incidence of postoperative infections than matched controls
      after colorectal surgery. ARF developed in 18.6% of patients. Preoperative
      optimization should include adequate hydration and assessment of potentially
      nephrotoxic substances for bowel preparation, preoperative antibiotics and pain
      control.

PMID- 22632257
TI  - Early intervention with a small molecule inhibitor for tumor necrosis factor
      alpha prevents cognitive deficits in a triple transgenic mouse model of
      Alzheimer's disease.
AB  - BACKGROUND: Chronic neuroinflammation is an important component of Alzheimer's
      disease and could contribute to neuronal dysfunction, injury and loss that lead
      to disease progression. Multiple clinical studies implicate tumor necrosis factor
      alpha as an inflammatory mediator of neurodegeneration in patients with
      Alzheimer's because of elevated levels of this cytokine in the cerebrospinal
      fluid, hippocampus and cortex. Current Alzheimer's disease interventions are
      symptomatic treatments with limited efficacy that do not address etiology. Thus,
      a critical need exists for novel treatments directed towards modifying the
      pathophysiology and progression. METHODS: To investigate the effect of early
      immune modulation on neuroinflammation and cognitive outcome, we treated triple
      transgenic Alzheimer's disease mice (harboring PS1(M146V), APP(Swe), and
      tau(P301L) transgenes) with the small molecule tumor necrosis factor-alpha
      inhibitors, 3,6'-dithiothalidomide and thalidomide, beginning at four months of
      age. At this young age, mice do not exhibit plaque or tau pathology but do show
      mild intraneuronal amyloid beta protein staining and a robust increase in tumor
      necrosis factor-alpha. After 10 weeks of treatment, cognitive performance was
      assessed using radial arm maze and neuroinflammation was assessed using
      biochemical, stereological and flow cytometric endpoints. RESULTS: 3,6'
      dithiothalidomide reduced tumor necrosis factor-alpha mRNA and protein levels in
      the brain and improved working memory performance and the ratio of resting to
      reactive microglia in the hippocampus of triple transgenic mice. In comparison to
      non-transgenic controls, triple transgenic Alzheimer's disease mice had increased
      total numbers of infiltrating peripheral monomyelocytic/granulocytic leukocytes
      with enhanced intracytoplasmic tumor necrosis factor-alpha, which was reduced
      after treatment with 3,6'-dithiothalidomide. CONCLUSIONS: These results suggest
      that modulation of tumor necrosis factor-alpha with small molecule inhibitors is
      safe and effective with potential for the long-term prevention and treatment of
      Alzheimer's disease.

PMID- 22632260
TI  - Richard Loeppky (1937-2012).

PMID- 22632262
TI  - Thematic issue-topic--diabetic cardiovascular disease--an unmet medical need:
      emerging targets and therapies-introduction to the special issue.
AB  - The major cause of death and complications in patients with type 2 diabetes is
      cardiovascular disease. Cardiovascular complications that are often associated
      with diabetes include heart failure, acute myocardial infarction (MI), peripheral
      vascular disease, and cerebrovascular disease. More than 60% of all patients with
      type 2 diabetes die of cardiovascular disease, and an even greater percentage
      have serious complications. The impact of glucose lowering on cardiovascular
      complications is a hotly debated issue and recent large clinical trials, the
      Action in Diabetes and Vascular Disease (ADVANCE), Action to Control
      Cardiovascular Risk in Diabetes (ACCORD) and Veterans Affairs Diabetes Trial
      (VADT) reported no significant decrease in cardiovascular events with intensive
      glucose control. Risk remains high even after correcting diabetes-associated
      dyslipidemia (high triglycerides and low HDL). Several mechanisms are likely to
      contribute to the accelerated atherosclerosis and increased cardiovascular
      disease risk seen in type 2 diabetics. Of these, postprandial
      hyperglycemia/lipemia, insulin resistance and inflammation may be the most
      important and under controlled contributing factors to vascular disease. The goal
      of this thematic issue is to address limitations of current therapies and review
      emerging research and therapeutic approaches that target inflammation, insulin
      resistance and other pathological mechanisms that contribute to cardiovascular
      disease in diabetes.

PMID- 22632261
TI  - Microbiological safety of a novel bio-artificial liver support system based on
      porcine hepatocytes: a experimental study.
AB  - BACKGROUND: Our institute has developed a novel bio-artificial liver (BAL)
      support system, based on a multi-layer radial-flow bioreactor carrying porcine
      hepatocytes and mesenchymal stem cells. It has been shown that porcine
      hepatocytes are capable of carrying infectious porcine endogenous retroviruses
      (PERVs) into human cells, thus the microbiological safety of any such system must
      be confirmed before clinical trials can be performed. In this study, we focused
      on assessing the status of PERV infection in beagles treated with the novel BAL.
      METHODS: Five normal beagles were treated with the novel BAL for 6 hours. The
      study was conducted for 6 months, during which plasma was collected from the BAL
      and whole blood from the beagles at regular intervals. DNA and RNA in both the
      collected peripheral blood mononuclear cells (PBMCs) and plasma samples were
      extracted for conventional PCR and reverse transcriptase (RT)-PCR with PERV
      specific primers and the porcine-specific primer Sus scrofa cytochrome B.
      Meanwhile, the RT activity and the in vitro infectivity of the plasma were
      measured. RESULTS: Positive PERV RNA and RT activity were detected only in the
      plasma samples taken from the third circuit of the BAL system. All other samples
      including PBMCs and other plasma samples were negative for PERV RNA, PERV DNA,
      and RT activity. In the in vitro infection experiment, no infection was found in
      HEK293 cells treated with plasma. CONCLUSIONS: No infective PERV was detected in
      the experimental animals, thus the novel BAL had a reliable microbiological
      safety profile.

PMID- 22632263
TI  - Diabetic CVD--soluble epoxide hydrolase as a target.
AB  - The incidence of cardiovascular diseases remains high in diabetic patients
      despite the optimization of blood glucose control and the therapeutic management
      of risk factors. One emerging promising pharmacological approach that may help to
      prevent the development of diabetic cardiovascular complications is to improve
      endothelial function through the restoration of the bioavailability of
      epoxyeicosatrienoic acids (EETs). EETs are crucial eicosanoid signaling molecules
      synthesized by cytochrome P450 epoxygenases in the vascular endothelium and in
      pancreatic islets. EETs promote vasodilatation and display attractive anti
      inflammatory and anti-aggregating actions together with potent effects on insulin
      release and sensitivity. In animal models of insulin-resistance and diabetes, a
      decrease in EET availability has been reported, and is a deleterious mechanism
      that probably contributes to multiple metabolic, cardiovascular and renal
      disorders in this setting. Moreover, increasing experimental evidence suggest
      that the use of soluble epoxide hydrolase (sEH) inhibitors, which prevent EET
      degradation, is a promising pharmacological approach to prevent endothelial
      dysfunction and to protect against target organ damage in metabolic diseases.
      This review presents evidence that the EET pathway is disturbed from the early
      stages of metabolic diseases, and analyzes the potential contribution of EETs
      impairment to the progression of cardiovascular diseases associated with
      diabetes. Pathophysiological and therapeutic perspectives are thereafter
      discussed, including the necessity to demonstrate the role of EET pathway
      alterations in endothelial dysfunction associated with diabetes in human, and the
      interest of sEH inhibitors to prevent the development of diabetic cardiovascular
      complications, with the expected result of improving patients' health.

PMID- 22632264
TI  - Diabetic cardiovascular disease--AMP-activated protein kinase (AMPK) as a
      therapeutic target.
AB  - Cardiovascular complications are the leading cause of death and morbidity in
      patients with diabetes; accounting for around 7 out of 10 of all causes of death
      in this population. Returning patients to normoglycaemia alone has been shown to
      have little effect on cardiovascular end points, therefore new therapies and
      strategies are required in order to reduce the incidence and improve outcomes of
      cardiovascular disease in diabetic individuals. The metabolic enzyme AMP
      activated protein kinase (AMPK) has emerged in recent years as an attractive
      potential therapeutic target for diabetic vascular disease, and studies have
      shown improved endothelial and smooth muscle cell function following AMPK
      activation. Additionally, improved lipid profiles, reduced hypertrophic
      cardiomyocyte growth and protection from cardiac ischaemia-reperfusion injury
      have also been observed as beneficial outcomes of AMPK therapy. In this review we
      will discuss in detail the potential downstream targets of AMPK activation in the
      cardiovascular system. We will also provide an overview of long-known and newly
      discovered direct and indirect AMPK activators, as well as novel synthesised AMPK
      activating compounds, which will highlight the potential for further exploiting
      AMPK in a therapeutic context for cardiovascular disease in diabetes.

PMID- 22632265
TI  - Diabetic CVD--focus on vitamin D.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality and morbidity
      among diabetics. Vitamin D deficiency is very common all over the world. Over
      last few years, vitamin D has been considered as an important regulating factor
      for cardiovascular health. Metabolic syndrome and obesity are highly prevalent in
      vitamin D deficient people. In fact all components of metabolic syndrome are
      affected by vitamin D. Vitamin D regulates insulin secretion and its action. It
      has also some controlling effect on Renin-Angiotensin system, which influences
      cardiomyocytes positively. Vitamin D plays a role in vascular system too. This
      vitamin reduces vascular calcification and inflammatory processes. Given the
      important role of Vitamin D in cardiovascular health, this review focuses on the
      impacts of vitamin D on the various CVD risk factors.

PMID- 22632266
TI  - Targeting mitochondrial oxidative stress through lipoic acid synthase: a novel
      strategy to manage diabetic cardiovascular disease.
AB  - Mitochondrial oxidative stress is a major etiological factor in the development
      of cardiovascular disease associated with type 2 diabetes. Hyperglycemia and
      insulin resistance contribute to the generation of excessive reactive oxygen
      species (ROS) which have damaging effects on various macromolecules within the
      mitochondria, leading to mitochondrial dysfunction. Mitochondrial damage within
      the endothelial cells lining the vasculature causes endothelial dysfunction, a
      critical event in atherosclerosis. In diabetes, deficiency of the antioxidant
      defense network prevents the generation of a robust response to counter the
      damaging effects of ROS. Since oxidative stress is the underlying factor for the
      damages inflicted by hyperglycemia, a logical therapeutic approach is to use
      antioxidants to quench ROS produced within the mitochondria. Lipoic acid (LA) is
      a potent mitochondrial antioxidant and an essential cofactor of alpha-ketoacid
      dehydrogenases. Clinical studies testing the effects of LA supplementation in
      diabetes and its complications have yielded promising results, especially with
      regard to management of diabetic neuropathy. Endogenously, LA is synthesized
      within the mitochondria by the enzyme, Lipoic acid synthase (LASY). This review
      describes a novel therapeutic approach which is aimed at increasing expression of
      LASY to enhance mitochondrial levels of LA. Such a strategy has the potential of
      improving mitochondrial function, reducing inflammation and insulin resistance,
      translating to better metabolic control in diabetes and preventing cardiovascular
      disease.

PMID- 22632268
TI  - The Intramolecular Impact to the Sequence Specificity of B->A Transition: Low
      Energy Conformational Variations in AA/TT and GG/CC Steps.
AB  - Abstract   It is well known, that local B->A transformation in DNA is involved in
      several biological processes. In vitro B<->A transition is sequence-specific. The
      physical basis of this specificity is not known yet. Here we analyze the effect
      of intramolecular interactions on the structural behavior of the GG/CC and AA/TT
      steps. These steps exemplify sequence specific bias to the B- or A-form
      structure. Optimization of potential energy of the molecular systems composed of
      an octanucle-otide, neutralized by Na(+) and solvated with TIP3P water molecules
      in rectangular box with periodic boundary conditions gives the statistically
      representative sets of low energy structures for GG/CC and AA/TT steps in the
      middle of the diverse flanking sequences. Permissible 3D variations of GG/CC and
      AA/TT, and correlation of the relative motion of base pairs in these steps were
      analyzed. AA/TT step permits high variability for low energy conformers in the B
      form DNA and small variability for low energy conformers in the A-form DNA. In
      contrast GG/CC step permits high variability for low energy conformers in the A
      form DNA and small variability for low energy conformers in the B-form DNA. The
      relative motion of base pairs in GG/CC step is high correlated, while in AA/TT
      step this correlation is notably less. Atom-atom interactions inside-the-step
      always favors the B-form and their component - stacking interactions (atomatom
      interactions between nucleic bases) is crucial for the duplex stabilization.
      Formation of the A-form for both steps is a result of interactions with the
      flanking sequences and water-cation environment in the box. The average energy
      difference between conformations presenting B-form and A-form for the GG/CC step
      is high, while for the AA/TT step it is rather low. Thus, intramolecular
      interactions in GG/CC and AA/TT steps affect the possible conformational
      diversity ("conformational entropy") of the A- and B- type structures of DNA
      step. This determines the known bias of the A-form DNA depending on the
      enrichment of sequences with GG/CC. If structural tuning during the process of
      protein-DNA complex formation lead to the local B->A transformation of DNA, it is
      largely directed by high conformational diversity of GG/CC step in the A-form. In
      such a case the presence in the target site of both kinds of examined steps
      ensures the reversible character of ligand binding.

PMID- 22632269
TI  - Dysfunction in cytochrome c oxidase caused by excessive nitric oxide in human
      lens epithelial cells stimulated with interferon-gamma and lipopolysaccharide.
AB  - PURPOSE: We previously found two mechanisms for the dysfunction in Ca(2+)
      regulation caused by excessive nitric oxide (NO) using the lenses of hereditary
      cataract model rats: the first is that NO causes a decrease in Adenosine-5'
      triphosphate (ATP) level via cytochrome c oxidase (CCO), resulting in a decrease
      in ATPase function; the second is that NO causes enhanced lipid peroxidation,
      resulting in the oxidative inhibition of Ca(2+)-ATPase. In this study, we
      demonstrate the effect of excessive NO on lipid peroxidation and ATP production
      in human lens using a human lens epithelial cell line, SRA 01/04 (human lens
      epithelial (HLE) cells). METHODS: Excessive NO via inducible NO synthase (iNOS)
      was induced by stimulating cells with a combination of interferon-gamma (1000 IU
      IFN-gamma) and lipopolysaccharide (100 ng/mL LPS). CCO activity was measured
      using a Mitochondrial Isolation kit and Cytochrome c Oxidase Assay kit, and ATP
      levels were determined using a Sigma ATP Bioluminescent Assay Kit and a
      luminometer AB-2200. RESULTS: Cytochrome c oxidase activity and ATP levels were
      decreased in HLE cells stimulated with IFN-gamma and LPS, and aminoguanidine (AG)
      and diethyldithiocarbamate (DDC) added 6 h before cell collection significantly
      attenuated these decreases in cells stimulated with the IFN-gamma and LPS for 24
      30 h. However, the lower CCO activity and ATP levels in HLE cells stimulated with
      the IFN-gamma and LPS for 30 h were not changed by treatment with AG or DDC for 6
      12 h, while the CCO activity and ATP levels in HLE cells treated with AG or DDC
      for 18 were recovered. CONCLUSION: Excessive NO causes a decrease in CCO activity
      and ATP levels, and the recovery time for CCO activity is related to exposure
      time to NO in HLE cells.

PMID- 22632267
TI  - Aldose reductase, oxidative stress and diabetic cardiovascular complications.
AB  - Cardiovascular disease represents the major cause of morbidity and mortality in
      patients with diabetes mellitus. Studies by us and others have implicated
      increased flux via aldose reductase (AR) as a key player in mediating diabetic
      complications, including cardiovascular complications. Data suggest that
      increased flux via AR in diabetics perpetuates increased injury after myocardial
      infarction, accelerates atherosclerotic lesion formation, and promotes restenosis
      via multiple mechanisms. Most importantly, studies have shown that increased
      generation of reactive oxygen species due to flux via AR has been a common
      feature in animal models of diabetic cardiovascular disease. Taken together,
      these considerations place AR in the center of biochemical and molecular stresses
      that characterize the cardiovascular complications of diabetes. Stopping AR
      dependent signaling may hold the key to interrupting cycles of cellular
      perturbation and tissue damage in diabetic cardiovascular complications.

PMID- 22632270
TI  - Disseminated tumour cells in bone marrow of patients with uveal melanoma.
AB  - PURPOSE: Approximately 50% of patients with uveal melanomas develop metastases.
      Thus, it is important to improve our understanding of how melanoma metastases
      develop. METHODS: As part of a uveal melanoma micrometastasis study, we compared
      the detection rates of immunomagnetically selected (IMS) tumour cells in bone
      marrow (BM) with positively stained tumour cells using immunocytochemistry (ICC).
      Bone marrow mononuclear cells were isolated. Immunocytochemistry cytospin
      preparations were immunocytochemically stained in parallel with two different
      melanoma antibodies, 9.2.27 and HMB45. Using IMS, melanoma cells were selected
      from BM mononuclear cell fractions using immunomagnetic beads coated with the
      9.2.27 antibody and identified by light microscopy. RESULTS: In cytospin
      preparations from 226 patients, melanoma cells were detected in 24 (10.6%), 10
      with 9.2.27 and 17 with the HMB45 antibody. In three cases, we found positive
      cells with both antibodies. Six of the 226 (2.6%) patients that stained
      positively with ICC died with metastatic disease, all also positive with IMS.
      Sixty-six (29.2%) patients had positive BM samples with IMS at the first
      examination. Immunomagnetic selection (IMS) was positive in 36.8% of the 57
      patients who later developed clinical metastases. Twenty-one IMS-positive
      patients and 31 IMS-negative patients died of metastases, in total 52 of 226
      patients (23.0%). The mortality rate of melanoma metastasis was 24% (6/24) after
      at least 4 1/2 years in ICC-positive patients compared to 38.5% (20/52) in IMS
      positive patients. CONCLUSION: The presence of melanoma cells in BM of patients
      with uveal melanoma is documented in our study with IMS and ICC.
      Immunomagnetically selected is more sensitive than ICC in detecting tumour cells
      in BM. However, statistically, we did not find any prognostic impact of the
      presence of melanoma cells in BM.

PMID- 22632271
TI  - Seed Fatty Acid Reducer acts downstream of gibberellin signalling pathway to
      lower seed fatty acid storage in Arabidopsis.
AB  - Previous studies based on microarray analysis have found that DELLAs down
      regulate several GDSL genes in unopened flowers and/or imbibed seeds. This
      suggests the role of DELLAs in seed fatty acid (FA) metabolism. In the present
      study, enhancement of gibberellin (GA) signalling through DELLA mutation or
      exogenous gibberellin acid A3 (GA(3) ) resulted in the up-regulated expression of
      transcription factors for embryogenesis and seed development, genes involved in
      the FA biosynthesis pathway, and five GDSL-type Seed Fatty Acid Reducer (SFAR)
      genes. SFAR overexpression reduced the total seed FA content and led to a
      particular pattern of seed FA composition. This 'SFAR footprint' can also be
      found in plants with enhanced GA(3)  signalling. By contrast, the loss of SFAR
      function dramatically increases the seed FA content. The transgenic lines that
      overexpress SFAR were less sensitive to stressful environments, reflected by a
      higher germination rate and better seedling establishment compared with the wild
      type (WT) plants. The GDSL-type hydrolyzer is a family of proteins largely
      uncharacterized in Arabidopsis. Their biological function remains poorly
      understood. SFAR reduces seed FA storage and acts downstream of the GA signalling
      pathway. We provide the first evidence that some GDSL proteins are somehow
      involved in FA degradation in Arabidopsis seeds.

PMID- 22632272
TI  - Comparative study of the value of dual tracer PET/CT in evaluating breast cancer.
AB  - The present study was conducted to assess the relationship between tumor uptake
      and pathologic findings using dual-tracer PET/computed tomography (CT) in
      patients with breast cancer. Seventy-four patients with breast cancer (mean age
      54 years) who underwent (11)C-choline and 2-[(18)F]fluoro-2-deoxy-d-glucose
      ((18)F-FDG) PET/CT prior to surgery on the same day were enrolled in the present
      study. Images were reviewed by a board-certified radiologist and two nuclear
      medicine specialists who were unaware of any clinical information and a consensus
      was reached. Uptake patterns and measurements of dual tracers were compared with
      the pathologic findings of resected specimens as the reference standard. Mean (+/
      SD) tumor size was 5.9 +/- 3.2 cm. All primary tumors were identified on (18)F
      FDG PET/CT and (11)C-choline PET/CT. However, (18)F-FDG PET/CT demonstrated focal
      uptake of the primary tumor with (n = 38; 51%) or without (n = 36; 49%) diffuse
      background breast uptake. Of the pathologic findings, multiple logistic
      regression analysis revealed an independent association between fibrocystic
      change and diffuse background breast uptake (odds ratio [OR] 8.57; 95% confidence
      interval [CI] 2.86-25.66; P < 0.0001). Tumors with higher histologic grade,
      nuclear grade, structural grade, nuclear atypia, and mitosis had significantly
      higher maximum standardized uptake values (SUV(max)) and tumor-to-background
      ratios (TBR) for both tracers. Multiple logistic regression analysis revealed
      that only the degree of mitosis was independently associated with a high SUV(max)
      (OR 7.45; 95%CI 2.21-25.11; P = 0.001) and a high TBR (OR 5.41; 95%CI 1.13-25.96;
      P = 0.035) of (11)C-choline PET/CT. In conclusion, (11)C-choline may improve
      tumor delineation and reflect tumor aggressiveness on PET/CT in patients with
      breast cancer.

PMID- 22632273
TI  - Shame-proneness in attempted suicide patients.
AB  - BACKGROUND: It has been suggested that shame may be an important feature in
      suicidal behaviors. The disposition to react with shame, "shame-proneness", has
      previously not been investigated in groups of attempted suicide patients. We
      examined shame-proneness in two groups of attempted suicide patients, one group
      of non-suicidal patients and one group of healthy controls. We hypothesized that
      the attempted suicide patients would be more shame-prone than non-suicidal
      patients and healthy controls. METHODS: The Test of Self-Conscious Affect
      (TOSCA), which is the most used measure of shame-proneness, was completed by
      attempted suicide patients (n = 175: 105 women and 3 men with borderline
      personality disorder [BPD], 45 women and 22 men without BPD), non-suicidal
      psychiatric patients (n = 162), and healthy controls (n = 161). The participants
      were convenience samples, with patients from three clinical research projects and
      healthy controls from a fourth research project. The relationship between shame
      proneness and attempted suicide was studied with group comparisons and multiple
      regressions. Men and women were analyzed separately. RESULTS: Women were
      generally more shame-prone than men of the same participant group. Female suicide
      attempters with BPD were significantly more shame-prone than both female suicide
      attempters without BPD and female non-suicidal patients and controls. Male
      suicide attempters without BPD were significantly less shame-prone than non
      suicidal male patients. In multiple regressions, shame-proneness was predicted by
      level of depression and BPD (but not by attempted suicide) in female patients,
      and level of depression and non-suicidality in male patients. CONCLUSIONS:
      Contrary to our hypothesis and related previous research, there was no general
      relationship between shame-proneness and attempted suicide. Shame-proneness was
      differentially related to attempted suicide in different groups of suicide
      attempters, with significantly high shame-proneness among female suicide
      attempters with BPD and a negative relationship between shame-proneness and
      attempted suicide among male patients. More research on state and trait shame in
      different groups of suicidal individuals seems clinically relevant.

PMID- 22632274
TI  - Beliefs about the harms of long-term use of nicotine replacement therapy:
      perceptions of smokers in England.
AB  - AIMS: Previous research has shown that a substantial proportion of smokers
      believe that nicotine causes serious diseases such as cancer, possibly deterring
      the use of nicotine replacement therapy (NRT) for smoking cessation or smoking
      reduction. This study examined beliefs about the harms specifically from long
      term use of NRT and associations between these and its use for smoking cessation
      and smoking reduction. DESIGN AND SETTING: Data were collected from 1657 smokers
      and recent ex-smokers involved in the Smoking Toolkit Study, a series of monthly
      household surveys of English adults aged 16 and over. MEASUREMENTS: Participants
      were asked if they thought the use of NRT for a year or more was harmful, and if
      so, to volunteer what they believed the harms to be. They were also asked if they
      were using NRT for smoking reduction and/or if they had used NRT in the past year
      during a quit attempt. FINDINGS: Six percent and 25% of smokers respectively,
      believed that the long term use of NRT was very or quit harmful to health; and a
      further 29% reported that they 'didn't know'. The most commonly reported harms
      were addiction and lung cancer. There was no association between these beliefs
      and use of NRT for smoking reduction or smoking cessation. CONCLUSION: A
      significant minority of smokers in England believe that the use of nicotine
      replacement therapy for a year or more is harmful. However, belief that long-term
      nicotine replacement therapy use can cause health harm does not appear to act as
      a deterrent to using it in a quit attempt or for smoking reduction.

PMID- 22632275
TI  - Hodgkin lymphoma presenting with multifocal osseous lesions in a child.

PMID- 22632276
TI  - The curriculum is dead! Long live the curriculum! Designing an undergraduate
      medicine and surgery curriculum for the future.
AB  - Where changing social circumstances demand reform of medicine, this in turn
      provokes new thinking in medical education. Curriculum changes, however, are
      often ill conceived, consisting of syllabus (content) modification, rather than
      careful consideration of fundamental principles and theory shaping a curriculum
      process initiative. The undergraduate medicine and surgery curriculum of the
      future must address some basic fault lines in current provision, such as medical
      culture's failure to democratise work practices ensuring patient safety. While
      acquiring a reputation as innovative and progressive, and after a decade of
      success with current provision, Peninsula Medical School (UK) has recognised the
      need to develop its curriculum for the future. Such a curriculum will be guided
      by best evidence from medical education to inform pedagogical practices and by
      sophisticated curriculum theory. Drawing on social learning pedagogies and
      curriculum reconceptualisation models for guidance, and incorporating evaluation
      of its current provision and published evaluations of other curricula
      (particularly Longitudinal Integrated models), fundamental principles were
      conceived to guide curriculum reform.

PMID- 22632277
TI  - Awarding global grades in OSCEs: evaluation of a novel eLearning resource for
      OSCE examiners.
AB  - BACKGROUND: A novel online resource has been developed to aid OSCE examiner
      training comprising a series of videos of OSCE performances that allow inter
      examiner comparison of global grade decisions. AIMS: To evaluate this training
      resource in terms of usefulness and ability to improve examiner confidence in
      awarding global grades in OSCEs. METHOD: Data collected from the first 200 users
      included global grades awarded, willingness to change grades following peer
      comparison and confidence in awarding grades before and after training. RESULTS:
      Most (86.5%) agreed that the resource was useful in developing global grade
      scoring ability in OSCEs, with a significant improvement in confidence in
      awarding grades after using the training package (p<0.001). CONCLUSIONS: This is
      a useful and effective online training package. As an adjunct to traditional
      training it offers a practical solution to the problem of availability of
      examiners.

PMID- 22632278
TI  - Patient instructors in rheumatology.
AB  - Patient instructors are patients trained to teach students in focussed history
      taking and/or examination in the context of the patient's specific illness. Their
      espousal has been quite extensively reported in rheumatology. The majority of
      studies show that patient instructors are effective in enhancing the knowledge
      and skills relevant to practice concerned with patients with the given conditions
      (in this case, typically rheumatoid arthritis and osteoarthritis). Most studies
      show patient instructors to be as effective as clinicians in this respect. They
      are especially effective at enhancing students' understanding of the impact of
      living with a chronic condition. With appropriate (quite extensive) training,
      they can also assess the examination skills of students, both undergraduate and
      postgraduate. Students value them, and the patient instructors themselves derive
      benefit from the activity. There are issues to be aware of regarding the adoption
      of patient instructors. The training required is significant. If employed as
      described in the literature, quite significant selection criteria come into play.
      In some cases, patient instructors feel under-rewarded financially; they should
      not be seen as medical education on the cheap. Nonetheless, patient instructors
      represent an excellent, relatively under-utilised, resource for the aiding of
      student learning in many areas of medicine.

PMID- 22632282
TI  - Intraoperative parathyroid hormone concentration to confirm removal of
      hypersecretory parathyroid tissue and time to postoperative normocalcaemia in
      nine dogs with primary hyperparathyroidism.
AB  - OBJECTIVE: To determine (1) whether the intraoperative parathyroid hormone
      concentration ([PTH]) during parathyroidectomy (PTX) can be used to indicate cure
      in dogs with primary hyperparathyroidism and (2) the time taken for postoperative
      serum calcium concentration to normalise. DESIGN: Retrospective study (2005-10)
      from a private referral hospital in Sydney, New South Wales, Australia.
      PROCEDURE: Nine client-owned dogs underwent surgical PTX for naturally occurring
      primary hyperparathyroidism. [PTH] was measured from serum samples taken
      immediately post-induction (pre-PTX]) and at least 20 min after adenoma removal
      (post-PTX) for all dogs, and during parathyroid gland manipulation (intra-PTX)
      for six dogs. The concentration of ionised calcium (iCa) was measured at various
      time points postoperatively until it normalised, then stabilised or decreased
      below reference ranges. Statistical analysis compared the mean pre-, intra- and
      post-PTX [PTH] and the average rate of decline of iCa concentration
      postoperatively. RESULTS: All dogs demonstrated a significant decrease from mean
      pre-PTX [PTH] (168.51 pg/mL) to mean post-PTX [PTH] (29.20 pg/mL). There was a
      significant increase in mean intra-PTX [PTH] (279.78 pg/mL). The average rate of
      decline of iCa concentration postoperatively to within the reference range (1.12
      1.40 mmol/L) occurred after 24 h. CONCLUSION: Intraoperative measurements of
      [PTH] can be used clinically to determine cure of primary hyperparathyroidism.
      Parathyroid hormone increases significantly during parathyroid gland
      manipulation. Plasma iCa concentration returns to within the reference range on
      average 24 h after successful PTX. Not all dogs require vitamin D or calcium
      supplementation pre- or postoperatively.

PMID- 22632283
TI  - Palliative radiation therapy in a dog with malignant trichoepithelioma.
AB  - An 11-year-old male Bearded Collie was brought to the Gifu University Animal
      Medical Centre with a skin mass on the lateral right thigh. Physical examination
      revealed a 30 * 65-mm oval mass with an alopecic and ulcerated surface.
      Histopathology of the surgically excised sample confirmed malignant
      trichoepithelioma. Five months after the surgery, the dog experienced lumbar pain
      resulting from metastasis to the lumbar vertebrae. Radiation therapy (RT) was
      performed and it alleviated the lumbar pain. Nine months after the surgery,
      multiple skin metastases were identified. RT was performed at each occurrence,
      which reduced the size of each tumour and resulted in a partial response;
      however, systemic metastasis occurred and the dog died 17 months after the
      initial surgery. Canine malignant trichoepithelioma is a rare tumour, so an
      effective treatment has not been determined. Data from our case study indicate
      that RT has potential for pain control of primary and metastatic malignant
      trichoepithelioma.

PMID- 22632285
TI  - Methiocarb poisoning of a horse in Australia.
AB  - Snail bait poisoning is rare in horses. Cases have been reported, but clinical
      signs and subsequent prognostic indicators have been poorly documented and must
      be extrapolated from cases in companion animals. We describe in detail the
      poisoning of a horse that consumed a lethal dose of the carbamate, methiocarb.
      There are currently no guidelines for treating equine methiocarb toxicoses, but
      the principles of management are based on supportive therapy.

PMID- 22632284
TI  - Idiopathic haemarthrosis in eight horses.
AB  - OBJECTIVES: To review eight horses diagnosed with idiopathic haemarthrosis and to
      describe the intra-articular use of yttrium-90 ((90) Y) and methylprednisolone
      acetate (MPA) in recurrent haemarthrosis cases. DESIGN: Retrospective case
      series. METHOD: The medical records, diagnostic images, histopathology and
      outcome of all horses diagnosed with idiopathic haemarthrosis between 1998 and
      2010 were reviewed. RESULTS: Four Thoroughbred racehorses with haemarthrosis of
      the antebrachiocarpal joint had severe acute lameness (median, grade 4) and
      marked joint effusion after high-speed exercise. Another four horses (2
      Thoroughbred racehorses, 1 Standardbred racehorse, 1 Warmblood) had haemarthrosis
      of the tarsocrural joint and presented with mild, intermittent lameness (median,
      grade 1) and marked, persistent joint effusion. Six of the eight horses had
      recurrent haemarthrosis prior to treatment. Radiographic and nuclear
      scintigraphic examinations did not identify bone pathology. Diagnostic
      arthroscopy (7 cases) identified grossly hypertrophied yellow/brown discoloured
      synovium. Synovial histopathology of these cases revealed chronic synovial
      hyperplasia with severe haemosiderosis and granulomatous inflammatory reaction of
      varying severity. All horses underwent rest, bandaging and phenylbutazone
      administration. Two horses had subtotal mechanical synovectomy, four horses had
      intra-articular administration of (90) Y and MPA, and one horse underwent both
      treatments. Seven cases returned to their previous use (median time, 7 months).
      Haemarthrosis recurred in three horses, two of which had received the (90) Y and
      MPA treatment. CONCLUSION: Idiopathic haemarthrosis should be considered a
      differential for acute and recurrent joint related lameness and effusion.
      Recurrence appears not uncommon and the use of intra-articular (90) Y and MPA in
      conjunction with a conservative management treatment protocol warrants further
      evaluation.

PMID- 22632286
TI  - Evaluation of serovar-independent ELISA antigens of Actinobacillus
      pleuropneumoniae in pigs, following experimental challenge with A.
      pleuropneumoniae, Mycoplasma hyopneumoniae and Pasteurella multocida.
AB  - OBJECTIVE: To compare the sensitivity and specificity of six serological enzyme
      linked immunosorbent assays (ELISAs) based on serovar-independent antigens of
      Actinobacillus pleuropneumoniae (App) and investigate cross-reactivity in disease
      free pigs challenged with Mycoplasma hyopneumoniae and Pasteurella multocida.
      DESIGN: Five experimental pig trials using direct challenge with App serovars 1,
      7 or 15 or direct challenge with M. hyopneumoniae and/or various dose rates of P.
      multocida. PROCEDURE: A 39-kDa outer membrane protein antigen and five
      recombinant antigens from the apxIVA gene of App were evaluated. The latter were
      derived from the ApxIVA N-terminus (ApxIVA-N, ApxIVA-NP, ApxIVA-NPS) or C
      terminus (ApxIVA-C, ApxIVA-CP). Pigs were sampled after challenge and clinical
      and necropsy findings evaluated. RESULTS: The 39-kDa ELISA had high sensitivity
      but lacked specificity, with significantly increased cross-reactivity following
      P. multocida challenge. ELISAs based on ApxIVA N-terminus antigens were
      significantly more sensitive than C-terminus antigens for the detection of App
      induced disease. Although ApxIVA-N and ApxIVA-NP ELISAs had increased reactivity
      following P. multocida challenge, they retained high specificity for App-induced
      disease (90-93%). Affinity purified ApxIVA-NP antigen had marginally better
      specificity than ApxIVA-N, without reduced sensitivity. Mycoplasma hyopneumoniae
      did not affect serological cross-reactivity. In disease-free pigs, the
      specificity of the ApxIVA-NPS ELISA may be adversely affected by nasal carriage
      of apparently low-virulence App strains. CONCLUSIONS: ApxIVA-N-based ELISAs can
      be used for evaluating App status in commercial herds, but some appear limited by
      high carriage rates of low-virulence App. The 39-kDa antigen is only of merit in
      exclusion of App disease by negative serology.

PMID- 22632287
TI  - An outbreak of severe iodine-deficiency goitre in a sheep flock in north-east
      Victoria.
AB  - BACKGROUND: Several outbreaks of goitre, considered to be related to iodine
      deficiency, occurred in sheep flocks throughout Victoria in 2010. OBJECTIVE: We
      describe one outbreak in Merino-Border Leicester-cross ewes and their lambs in
      north-east Victoria that appeared to be associated with increased rainfall and
      pasture growth, particularly during the preceding summer and autumn. RESULTS: The
      outbreak was characterised by a four-fold increase in neonatal lamb deaths and
      goitre, alopecia and poor skeletal development in the lambs. Most cases occurred
      in lambs born to 2-year-old crossbred ewes that had grazed long, lush perennial
      pastures throughout their entire pregnancy, whereas few cases occurred in mature
      crossbred or Merino ewes that had grazed shorter, annual pastures on hill country
      for 3 weeks in late pregnancy but were otherwise managed similarly. CONCLUSION:
      Existing recommendations for south-eastern Australia are that only spring-lambing
      ewes in iodine-deficient areas require iodine supplementation to prevent goitre
      in years with high autumn-winter rainfall. Aspects of this outbreak suggest that
      ewes lambing at other times of the year and grazing abundant pasture for
      prolonged periods may also require supplementation to prevent goitre, even if
      autumn-winter rainfall does not exceed previously established thresholds.

PMID- 22632288
TI  - Medetomidine immobilisation and atipamezole reversal in large estuarine
      crocodiles (Crocodylus porosus) using metabolically scaled dosages.
AB  - BACKGROUND: Restraint of large estuarine crocodiles is potentially dangerous.
      Neuromuscular blockers and other immobilising drugs have been used with variable
      results. Medetomidine has been reported as a reliable, repeatable and reversible
      immobilisation agent in small estuarine crocodilians. METHODS AND RESULTS: Two
      wild and two farmed male animals, between 3.05 and 4.6 m long, were hand-injected
      into a triceps muscle with a metabolically scaled medetomidine dosage.
      Immobilisation occurred within 30 min. At the conclusion of the procedures, 70
      min after medetomidine administration, three animals were injected with
      atipamezole IM into the opposite triceps muscle at a dosage based on body surface
      area. Reversal occurred within 5 min. The fourth animal was intubated prior to
      reversal of medetomidine and maintained on isoflurane anaesthesia for a
      gastrotomy. All animals were monitored closely post recovery and then regularly
      for at least 1 week. CONCLUSIONS: Medetomidine at a metabolically scaled dosage
      delivered IM into the forelimb was effective for immobilising large estuarine
      crocodiles for at least 40 min. Atipamezole administered at a dosage calculated
      as a function of surface area effectively reversed this immobilisation.

PMID- 22632289
TI  - Conceptual framework of acute care nurse practitioner role enactment, boundary
      work, and perceptions of team effectiveness.
AB  - AIM: This article describes a new conceptual framework for acute care nurse
      practitioner role enactment, boundary work and perceptions of team effectiveness.
      BACKGROUND: Acute care nurse practitioners contribute positively to patient care
      by enacting an expanded scope of practise. Researchers have found both positive
      and negative reactions to the introduction of acute care nurse practitioners in
      healthcare teams. The process of role enactment, shifting role boundaries, and
      perceptions of team effectiveness has been studied disparately. A framework
      linking team structures and processes to desirable outcomes is needed. DATA
      SOURCES: Literature was obtained by searching CINAHL, PsycInfo, MedLine, PubMed,
      British Nursing Index, Cochrane Library, JSTOR Archive, Web of Science, and
      Google Scholar from 1985-2010. A descriptive multiple-case study was completed
      from March 2009-May 2009. DISCUSSION: A new conceptual framework describing how
      role enactment and boundary work affect perceptions of team effectiveness was
      developed by combining theoretical and empirical sources. The framework proposes
      proximal indicators used by team members to assess their team's performance.
      IMPLICATIONS FOR NURSING: The framework identifies the inter-related dimensions
      and concepts that different stakeholders need to consider when introducing nurse
      practitioners in healthcare teams. Further study is needed to identify team-level
      outcomes that reflect the contributions of all providers to quality patient care,
      and explore the patients' and families' perceptions of team effectiveness
      following the introduction of acute care nurse practitioners. CONCLUSION: The new
      framework can guide decision-making and research related to the structures,
      processes, and outcomes of nurse practitioner roles in healthcare teams.

PMID- 22632290
TI  - Occupational stress and psychopathology in health professionals: an explorative
      study with the multiple indicators multiple causes (MIMIC) model approach.
AB  - Occupational stress is a multivariate process involving sources of pressure,
      psycho-physiological distress, locus of control, work dissatisfaction,
      depression, anxiety, mental health disorders, hopelessness, and suicide ideation.
      Healthcare professionals are known for higher rates of occupational-related
      distress (burnout and compassion fatigue) and higher rates of suicide. The
      purpose of this study was to explain the relationships between occupational
      stress and some psychopathological dimensions in a sample of health
      professionals. We investigated 156 nurses and physicians, 62 males and 94
      females, who were administered self-report questionnaires to assess occupational
      stress [occupational stress inventory (OSI)], temperament (temperament evaluation
      of Memphis, Pisa, Paris, and San Diego autoquestionnaire), and hopelessness (Beck
      hopelessness scale). The best Multiple Indicators Multiple Causes model with five
      OSI predictors yielded the following results: chi2(9) = 14.47 (p = 0.11); chi2/df
      = 1.60; comparative fit index = 0.99; root mean square error of approximation =
      0.05. This model provided a good fit to the empirical data, showing a strong
      direct influence of casual variables such as work dissatisfaction, absence of
      type A behavior, and especially external locus of control, psychological and
      physiological distress on latent variable psychopathology. Occupational stress is
      in a complex relationship with temperament and hopelessness and also common among
      healthcare professionals.

PMID- 22632359
TI  - The contribution of experiential avoidance and social cognitions in the
      prediction of social anxiety.
AB  - BACKGROUND: Cognitive models propose that social anxiety arises from specific
      dysfunctional cognitions about the likelihood and severity of embarrassment.
      Relational frame theory (RFT), on the other hand, posits that social anxiety
      arises from the unwillingness to endure unpleasant internal experiences (i.e.
      experiential avoidance [EA]). Although cognitive models have garnered empirical
      support, it may be that newer models such as RFT can improve our ability to
      predict and treat social anxiety. AIMS: We aimed to elucidate the relationship
      between dysfunctional cognitions and EA, as well as their independent and
      relative contributions to the prediction of social anxiety symptoms. We
      hypothesized that dysfunctional cognitions and EA would each be associated with
      social anxiety, as well as with each other. We also predicted that both EA and
      dysfunctional cognitions would remain independent predictors of social anxiety
      symptoms after controlling for each other and general distress. METHOD:
      Undergraduates high (n = 173) and low (n = 233) in social anxiety completed
      measures of social anxiety, dysfunctional cognitions, EA, and general distress.
      The overall sample was 66.3% female; mean age = 20.01 years (SD = 2.06). RESULTS:
      Correlational analyses revealed that EA, dysfunctional cognitions, and social
      anxiety symptoms were moderately correlated with one another. Additionally,
      hierarchical regression analyses revealed that dysfunctional cognitions predicted
      social anxiety symptoms even after controlling for EA; the reverse was not found.
      CONCLUSIONS: RESULTS suggest that EA and social anxiety specific cognitive
      distortions overlap to a moderate extent. EA does not add to the prediction of
      social anxiety symptoms above and beyond dysfunctional cognitions. Additional
      theoretical and treatment implications of the results are discussed.

PMID- 22632360
TI  - Graves' ophthalmopathy and dermopathy. Preface.

PMID- 22632361
TI  - Evaluating Graves' orbitopathy.
AB  - Graves' Orbitopathy (GO) is an immune-mediated disorder causing inflammation and
      expansion of orbital fat and muscle. The resulting spectrum of ocular and orbital
      changes may cause significant visual and cosmetic morbidity and are graded as
      disease severity. The disease follows a biphasic course with an active or
      progressive phase followed by a quiescent or stable phase: the temporal status is
      graded as disease activity. Grading systems for GO include Werner's NO SPECS and
      European Group on Graves' Orbitopathy (EUGOGO)'s severity scales, the Clinical
      Activity Score (CAS) and the VISA Classification (for severity and activity).
      Diagnosis of GO is based on recognition of clinical features and may be supported
      by thyroid function and immune testing, and orbital imaging. The endocrinologist
      or internist may play an important role in early recognition and diagnosis of GO,
      in grading severity and activity, and in arranging appropriate referral to an
      ophthalmologist based on this evaluation.

PMID- 22632362
TI  - Ethnic differences in the clinical presentation of Graves' ophthalmopathy.
AB  - Ethnic differences in a number of eye conditions have been described. The
      literature on ethnic differences in Graves' ophthalmopathy (GO) is limited. There
      is some evidence to suggest Asian patients with GO may manifest milder phenotypic
      features of GO, with less proptosis and evidence of extraocular muscle
      involvement and restriction. The reasons for these differences are likely to be
      multifactorial and include orbital and lid anatomy, genetic background and
      autoimmune responses including TSH -receptor antibodies. These differences should
      be kept in mind when evaluating and managing patients with GO.

PMID- 22632363
TI  - Neuroimaging of Graves' orbitopathy.
AB  - Neuroimaging of Graves' orbitopathy (GO) plays an important role in the
      differential diagnosis and interdisciplinary management of patients with GO.
      Orbital imaging is required in unclear or asymmetric proptosis, in suspected
      optic neuropathy and prior to decompression surgery. Especially computed
      tomography and magnetic resonance (MR) imaging show the actual objective
      morphological findings, quantitative MR imaging giving additional information
      concerning the acuteness or chronicity of the disease. Major morphological
      diagnostic criteria include a spindle like spreading of the rectus muscles
      without involvement of the tendon, a compression of the optic nerve in the
      orbital apex (crowded orbital apex syndrome) and the absence of any space
      occupying intraorbital process. A longer lasting course of the disease may lead
      to a corresponding impression of the lamina papyracae, the normally parallel
      configured medial wall of the orbit, similar to a spontaneous decompression.

PMID- 22632364
TI  - Epidemiology of Graves' orbitopathy (GO) and relationship with thyroid disease.
AB  - The incidence of Graves' orbitopathy (GO) is 16/100,000 in females and
      2.9/100,000 in males as studied in Olmsted county. It can be calculated that the
      approximate prevalence is 0.25%. There is a gender bimodal distribution. Go
      usually occurs at the time of onset of the hyperthyroidism but may present up to
      a year before that time or as long as 5 years afterwards. Around 10-15% of
      patients have never been hyperthyroid and some are hypothyroid at GO
      presentation. Although the incidence of GO has probably been decreasing during
      the last 2 decades definite figures for this assertion are not available. Risk
      factors that may influence the incidence of GO include cigarette smoking and
      radioiodine treatment of hyperthyroidism. There are also complex genetic factors
      with multiple susceptibility alleles that contribute to the expression of the
      disease. The probability is that a reduction of the incidence of GO will be
      achieved by influencing the environmental factors.

PMID- 22632365
TI  - Immunopathogenesis of Graves' ophthalmopathy: the role of the TSH receptor.
AB  - Graves' ophthalmopathy is an inflammatory autoimmune disorder of the orbit. The
      close clinical and temporal relationships between Graves' hyperthyroidism and
      ophthalmopathy have long suggested that both conditions derive from a single
      systemic process and share the thyrotropin receptor as a common autoantigen. This
      receptor is expressed not only in thyroid follicular cells, but also in orbital
      fibroblasts with higher levels measured in orbital cells from ophthalmopathy
      patients than in cells from normal individuals. Recent studies from several
      laboratories have shown that thyrotropin receptor activation in orbital
      fibroblasts enhances hyaluronic acid synthesis and adipogenesis, both cellular
      functions that appear to be upregulated in the diseased orbit. The
      phosphoinositide 3-kinase/Akt signaling cascade, along with other effector
      pathways including adenylyl cyclase/cAMP, appears to mediate these processes.
      Future therapies for this condition may involve inhibition of thyrotropin
      receptor signaling in orbital fibroblasts.

PMID- 22632367
TI  - Management plan and delivery of care in Graves' ophthalmopathy patients.
AB  - Most patients with Graves' orbitopathy have mild disease that requires no or
      minimal intervention. For the minority of patients with moderate or severe
      disease, multiple medical and surgical treatments may be required at different
      stages. It is crucial that such patients are monitored closely and treatments
      applied with care in the right sequence. Medical treatments should be used as
      early as possible and only during the active phase of the disease. Rehabilitative
      surgery is indicated in the inactive phase of the disease and should follow the
      sequence: surgical decompression followed by eye muscle surgery, followed by lid
      surgery. Delivery of care in a coordinated fashion that makes use of best
      available expertise is important and best implemented through a Combined Thyroid
      Eye clinic.

PMID- 22632368
TI  - Treating the thyroid in the presence of Graves' ophthalmopathy.
AB  - The etiology of Graves' orbitopathy (GO) remains enigmatic. Optimal therapeutic
      choices for the hyperthyroidism associated with Graves' disease (GD) in the
      presence of GO remain controversial. Whether antithyroid drugs (ATDs),
      radioiodine (RAI), or thyroidectomy should be favored in such patients remains
      debated. Pre-therapy variables such as ethnicity, sex, age, thyroid function,
      level of TSH-receptor antibodies and smoking behavior influence response to
      therapy. Among the most important management goals are restoring euthyroidism and
      abstaining from smoking. On average, ATDs and thyroidectomy - independent of
      extent - do not influence the natural course of GO. RAI can cause de novo
      development or progression of GO, which is largely preventable with oral steroid
      prophylaxis. In patients with mild GO, the thyroid treatment is largely
      independent of GO. Moderate to severe GO should be treated promptly. Deciding
      whether, in the latter, GD is better treated with ATDs, RAI, or surgery, is based
      more on expert opinion than on evidence. It is clear that in the individual
      patient a number of factors, not addressed in any trial, influence the final
      choice of therapy for GD, including concern of developing or negatively affecting
      pre-existing GO. Evidently, there is room for improving therapy of GO. Progress
      using novel drugs such as rituximab, which might potentially influence positively
      both GD and GO, are impatiently awaited.

PMID- 22632369
TI  - Treatment of mild, moderate-to-severe and very severe Graves' orbitopathy.
AB  - Treatment of Graves' orbitopathy (GO) is better performed through a
      multidisciplinary approach. Euthyroidism should be promptly restored. Antithyroid
      drug and thyroidectomy are not disease-modifying treatments, whereas radioiodine
      may be associated with worsening of GO. This risk is eliminated by glucocorticoid
      prophylaxis. Treatments for GO differ depending on its severity and activity.
      Mild forms should be treated with local measures. In addition a course of
      selenium may be beneficial. Glucocorticoids (oral or intravenous) represent the
      main treatment of moderate-to-severe GO, the intravenous route being more
      effective. Weekly pulses of methylprednisolone are used and the cumulative dose
      should not exceed 8 g. Severe adverse events have been reported, particularly
      with higher doses. Orbital radiotherapy can be used either alone or associated
      with glucocorticoids. In very severe sight-threatening GO high dose intravenous
      glucocorticoid should be the initial treatment, orbital decompression being
      considered in nonresponding patients. Rehabilitative surgery should be deferred
      until GO becomes inactive.

PMID- 22632370
TI  - Surgical treatment of Graves' ophthalmopathy.
AB  - The aims of surgical treatment in Graves's orbitopathy (GO) are improvement of
      function and appearance. Since antiinflammatory treatment of GO rarely results in
      a complete resolution of symptoms, surgical treatment is very important for
      patients well being. Rehabilitative surgery includes orbital decompression,
      squint correction, lid lengthening and blepharoplasty and these procedures have
      to be performed in centres of expertise. Various techniques have been developed
      for orbital decompression which allow now a graded approach to proptosis
      reduction and optic nerve decompression in emergency situations. Extraocular
      muscle recessions can be successfully performed to treat most of the patients
      with diplopia. Only large or complex squint angles are difficult to treat and
      step by step procedures are recommended in these patients. Lid lengthening
      procedures are performed most often in GO patients and should be performed under
      local anaesthesia to get a good result. Serious complications are rare.

PMID- 22632366
TI  - Role of insulin-like growth factor-1 (IGF-1) pathway in the pathogenesis of
      Graves' orbitopathy.
AB  - The etiology of Graves' orbitopathy (GO) remains enigmatic and thus controversy
      surrounds its pathogenesis. The role of the thyroid stimulating hormone receptor
      (TSHR) and activating antibodies directed against it in the hyperthyroidism of
      Graves' disease (GD) is firmly established. Less well elucidated is what part the
      TSHR pathway might play in the development of GO. Also uncertain is the
      participation of other cell surface receptors in the disease. Elevated levels of
      insulin-like growth factor-1 receptor (IGF-1R) have been found in orbital
      fibroblasts as well as B and T cells from patients with GD. These abnormal
      patterns of IGF-1R display are also found in rheumatoid arthritis and carry
      functional consequences. In addition, activating IgGs capable of displacing IGF-1
      from IGF-1R have also been detected in patients with these diseases. IGF-1R forms
      a complex with TSHR which is necessary for at least some of the non-canonical
      signaling observed following TSHR activation. Functional TSHR and IGF-1R have
      also been found on fibrocytes, CD34+ bone marrow-derived cells from the monocyte
      lineage. Levels of TSHR on fibrocytes greatly exceed those found on orbital
      fibroblasts. When ligated by TSH or M22, a TSHR-activating monoclonal antibody,
      fibrocytes produce extremely high levels of several cytokines and chemokines.
      Moreover, fibrocytes infiltrate both the orbit and thyroid in GD. In sum, based
      on current evidence, IGF-1R and TSHR can be thought of as "partners in crime".
      Involvement of the former probably transcends disease boundaries, while TSHR may
      not.

PMID- 22632371
TI  - Quality of life in Graves' ophthalmopathy.
AB  - General health-related quality-of-life (QoL) questionnaires (MOS SF-24 and SF-36)
      and the more sensitive disease-specific QoL questionnaire (GO-QoL) both indicate
      substantial impairment of quality of life in patients with Graves' ophthalmopathy
      (GO). The GO-QoL contains 8 questions on visual functioning and 8 questions on
      appearance; answers on each subscale are transformed to scores ranging from 0
      (worst) to 100 (best). The minimal clinically important difference in scores is
      >=10 points for invasive therapies, but a change of 6 points on one of both
      subscales is already perceived by patients as beneficial and associated with an
      important change in daily functioning. The GO-QoL is well validated, widely used,
      and available in eight languages. The GO-QoL is recommended as an independent
      primary outcome measure in randomized clinical trials. Incorporating the GO-QoL
      in the routine assessment of GO in daily clinical practice is also recommended:
      although unproven, it is likely to improve the quality of care by identifying
      patients who are in need for psychological support in order to address poor
      psychosocial functioning and low self-esteem.

PMID- 22632372
TI  - Prevention of Graves' ophthalmopathy.
AB  - Smoking is the most important risk factor for the occurrence/progression of
      Graves' ophthalmopathy (GO), as well as for its lower/slower response to
      immunosuppression. Accordingly, refrain from smoking should be urged, both as
      primary prevention (removal of risk factors in Graves' patients without GO),
      secondary prevention (early detection and treatment of asymptomatic/very mild GO)
      and tertiary prevention (reduction of complications/disability of overt GO). A 6
      month course of 200 MUg/day sodium selenite can prevent progression of mild GO to
      more severe GO and is, therefore, a form of secondary prevention and, probably,
      primary prevention. Correction of thyroid dysfunction and stable maintenance of
      euthyroidism are important preventive measures. The optimal treatment for
      hyperthyroidism in patients with GO is uncertain, because evidence demonstrating
      the superiority of antithyroid drugs over thyroid ablation (radioiodine,
      thyroidectomy, or both) is lacking. If radioiodine is used, low-dose steroid
      prophylaxis is recommended, particularly in smokers, to prevent radioiodine
      associated GO progression.

PMID- 22632373
TI  - Thyroid microcarcinoma.
AB  - Nowadays the most commonly occurring differentiated thyroid cancer in many
      countries is a microcarcinoma in patients older than 45 years, incidentally found
      during neck ultrasound. In view of their low morbidity and mortality, the crucial
      point is how to manage such microcarcinomas. Recently published European and
      American guidelines aim to minimize the diagnostic and therapeutic procedures
      without affecting the diagnostic accuracy and the therapeutic effectiveness,
      keeping in mind that we are dealing with patients who have a normal life
      expectancy and to whom we have to guarantee an excellent quality of life. The
      present review will summarize the clinical and pathological features of thyroid
      microcarcinoma, including its definition, prevalence, presentation, pathology,
      genetic, clinical impact and will try to derive from them a rationale for
      therapeutic and diagnostic intervention.

PMID- 22632374
TI  - Preparation of C2-symmetric allenes by palladium-catalyzed double-nucleophilic
      substitution on 3-bromopenta-2,4-dienyl acetate.
AB  - Easily accessible 3-bromopenta-2,4-dienyl acetate was applied to the palladium
      catalyzed reaction with soft nucleophiles. The reaction proceeded through the
      stepwise 2-fold nucleophilic substitution via formal S(N)2' and S(N)2 processes
      giving the various doubly functionalized C(2)-symmetric allenes in good yields.

PMID- 22632375
TI  - Defense mechanisms of Pseudomonas aeruginosa PAO1 against quantum dots and their
      released heavy metals.
AB  - The growing use of quantum dots (QDs) in numerous applications increases the
      possibility of their release to the environment. Bacteria provide critical
      ecosystem services, and understanding their response to QDs is important to
      assess the potential environmental impacts of such releases. Here, we analyze the
      microbial response to sublethal exposure to commercial QDs, and investigate
      potential defense and adaptation mechanisms in the model bacterium Pseudomonas
      aeruginosa PAO1. Both intact and weathered QDs, as well as dissolved metal
      constituents, up-regulated czcABC metal efflux transporters. Weathered QDs also
      induced superoxide dismutase gene sodM, which likely served as a defense against
      oxidative stress. Interestingly, QDs also induced antibiotic resistance (ABR)
      genes and increased antibiotic minimum inhibitory concentrations by 50 to 100%,
      which suggests up-regulation of global stress defense mechanisms. Extracellular
      synthesis of nanoparticles (NPs) was observed after exposure to dissolved
      Cd(NO(3))(2) and SeO(2). With extended X-ray absorption fine structure (EXAFS),
      we discerned biogenic NPs such as CdO, CdS, CdSe, and selenium sulfides. These
      results show that bacteria can mitigate QD toxicity by turning on energy
      dependent heavy-metal ion efflux systems and by mediating the precipitation of
      dissolved metal ions as less toxic and less bioavailable insoluble NPs.

PMID- 22632377
TI  - Safety and efficacy of pharmacological cardioversion of atrial fibrillation using
      intravenous vernakalant, a new antiarrhythmic drug with atrial selectivity.
AB  - INTRODUCTION: Atrial fibrillation (AF) is the most common sustained cardiac
      arrhythmia that due to its frequent hospitalizations and increased complication
      rates imposes a significant health economic burden. Many patients with recurrent
      AF are admitted to the hospital for cardioversion to restore sinus rhythm. Given
      this knowledge, it is clearly important to identify a feasible and effective
      approach for cardioversion of these patients. Cardioversion always requires
      careful assessment of potential complications, which apart from thromboembolic
      risks, include proarrhythmias and those related to the deep sedation required for
      electrical cardioversion. Even though electrical cardioversion is proven to be
      safe and effective, the need for anesthesia makes alternative strategies more
      attractive. AREAS COVERED: The research discussed is the alternative strategies
      for cardioversion, including electrical cardioversion and the new relatively
      atrial-selective antiarrhythmic drug, vernakalant. The literature search
      methodology undertaken included search in PubMed (cardioversion, vernakalant,
      conversion as key words). EXPERT OPINION: Vernakalant is shown to have good
      conversion rates, an apparently safe antiarrhythmic profile and is well tolerated
      in patients with a history of ischemic heart disease. In most cases of recent
      onset AF, pharmacological cardioversion can provide a probably more cost
      effective and safer alternative to electrical cardioversion, which can then be
      used as a second option for those who failed the first attempt of cardioversion.

PMID- 22632376
TI  - Default in plasma and intestinal IgA responses during acute infection by simian
      immunodeficiency virus.
AB  - BACKGROUND: Conflicting results regarding changes in mucosal IgA production or in
      the proportions of IgA plasma cells in the small and large intestines during HIV
      infection have been previously reported. Except in individuals repeatedly exposed
      to HIV-1 but yet remaining uninfected, HIV-specific IgAs are frequently absent in
      mucosal secretions from HIV-infected patients. However, little is known about the
      organization and functionality of mucosal B-cell follicles in acute HIV/SIV
      infection during which a T-dependent IgA response should have been initiated. In
      the present study, we evaluated changes in B-cell and T-cell subsets as well as
      the extent of apoptosis and class-specific plasma cells in Peyer's Patches,
      isolated lymphoid follicles, and lamina propria. Plasma levels of IgA, BAFF and
      APRIL were also determined. RESULTS: Plasma IgA level was reduced by 46% by 28
      days post infection (dpi), and no IgA plasma cells were found within germinal
      centers of Peyer's Patches and isolated lymphoid follicles. This lack of a T
      dependent IgA response occurs although germinal centers remained functional with
      no sign of follicular damage, while a prolonged survival of follicular CD4+ T
      cells and normal generation of IgG plasma cells is observed. Whereas the average
      plasma BAFF level was increased by 4.5-fold and total plasma cells were 1.7 to
      1.9-fold more numerous in the lamina propria, the relative proportion of IgA
      plasma cells in this effector site was reduced by 19% (duodemun) to 35% (ileum)
      at 28 dpi. CONCLUSION: Our data provide evidence that SIV is unable to initiate a
      T-dependent IgA response during the acute phase of infection and favors the
      production of IgG (ileum) or IgM (duodenum) plasma cells at the expense of IgA
      plasma cells. Therefore, an early and generalized default in IgA production takes
      place during the acute of phase of HIV/SIV infection, which might impair not only
      the virus-specific antibody response but also IgA responses to other pathogens
      and vaccines as well. Understanding the mechanisms that impair IgA production
      during acute HIV/SIV infection is crucial to improve virus-specific response in
      mucosa and control microbial translocation.

PMID- 22632378
TI  - Impact of the bowel-screening programme on the diagnosis of colorectal cancer in
      Ayrshire and Arran.
AB  - AIM: Bowel screening aims to reduce colorectal-cancer mortality by the detection
      and treatment of early-stage asymptomatic disease and the removal of precancerous
      adenomas. Bowel screening started in Ayrshire and Arran in September 2007. We
      report the impact of this screening on the diagnosis and stage of colorectal
      cancer and characterize screen-detected cancers in comparison with those
      diagnosed through other pathways. METHOD: Diagnoses were identified from an audit
      database. Referrals were grouped into screen detected, routine, urgent and
      emergency presentations. RESULTS: Between January 2001 and December 2010, 2289
      diagnoses of colorectal cancer were made. From 2001 to 2006, the mean (range)
      number of new colorectal-cancer diagnoses per year was 210 (198-220). Between
      2007 and 2010, the mean (range) number of diagnoses per year was 256 (239-274), a
      significant (P = 0.008) increase. Since September 2007, 877 colorectal cancers
      have been diagnosed: 17% were screen detected; 11% were detected as a result of
      routine GP referral; 51% were detected after urgent GP referral; and 21% were
      emergency presentations. TNM stage increased with urgency of referral.
      Approximately two-thirds (66%) of screen-detected colorectal cancers were node
      negative vs 25% of emergency presentations (P < 0.001). Most screen-detected
      cancers were distal to the splenic flexure (75%). Screened cancers had favourable
      pathology; lower T and N stages (both P < 0.001), less venous invasion (P <
      0.001) and better differentiation (P < 0.05). Similar results were seen after
      stratification for TNM stage. Screening has not yet resulted in a significant
      shift towards early-stage disease since 2007. CONCLUSION: Screening has been
      associated with an increase in the numbers of both new and early-stage colorectal
      cancers. Screen-detected cancers are predominantly early-stage disease with
      favourable pathology. At present, it remains to be seen whether screening will
      ultimately translate into an overall reduction in advanced-stage disease.

PMID- 22632379
TI  - Morphological and dimensional control via hierarchical assembly of doped
      oligoaniline single crystals.
AB  - Single crystals of doped aniline oligomers are produced via a simple solution
      based self-assembly method. Detailed mechanistic studies reveal that crystals of
      different morphologies and dimensions can be produced by a "bottom-up"
      hierarchical assembly where structures such as one-dimensional (1-D) nanofibers
      can be aggregated into higher order architectures. A large variety of crystalline
      nanostructures including 1-D nanofibers and nanowires, 2-D nanoribbons and
      nanosheets, 3-D nanoplates, stacked sheets, nanoflowers, porous networks, hollow
      spheres, and twisted coils can be obtained by controlling the nucleation of the
      crystals and the non-covalent interactions between the doped oligomers. These
      nanoscale crystals exhibit enhanced conductivity compared to their bulk
      counterparts as well as interesting structure-property relationships such as
      shape-dependent crystallinity. Furthermore, the morphology and dimension of these
      structures can be largely rationalized and predicted by monitoring molecule
      solvent interactions via absorption studies. Using doped tetraaniline as a model
      system, the results and strategies presented here provide insight into the
      general scheme of shape and size control for organic materials.

PMID- 22632380
TI  - Is there a case for diaphragm pacing for amyotrophic lateral sclerosis patients?
AB  - Respiratory pacing has advanced the long-term management of respiratory failure
      secondary to neurological disorders. It has an established role in curtailing
      invasive mechanical ventilation after upper motor neuron lesions such as spinal
      cord injury. There is increasing interest to expand the application of
      intramuscular diaphragm pacing to amyotrophic lateral sclerosis (ALS), a
      progressive and fatal neurodegenerative disease. Although diaphragm pacing has
      been offered to ALS patients, evidence-based data to determine its benefits
      remain lacking. The limited current literature indicates progression of
      respiratory dysfunction in ALS patients despite diaphragm pacing. The data from
      clinical trials are inadequate to substantiate its survival and sleep benefits.
      Its advantages over non-invasive mechanical ventilation have not been directly
      investigated. Furthermore, there are cautions for ALS patients to consider when
      opting for diaphragm pacing. Progressive degeneration of the phrenic motor
      neurons in classic ALS will interrupt the transmission of pacer signals to
      sustain diaphragm contractions. Pacing protocols that are safe for other
      neurological conditions may be detrimental for ALS, at least as suggested by
      transgenic animal models. Issues inherent to the device warrant expert
      intervention in implanted patients. At present, clinical effectiveness and long
      term safety concerns about diaphragm pacing in ALS remain to be addressed.

PMID- 22632382
TI  - LASIK operations with the Ziemer FEMTO LDV femtosecond laser flap creation after
      previous photorefractive keratometry or laser-assisted sub-epithelial
      keratomileusis.

PMID- 22632381
TI  - ERAP1 genetic variations associated with HLA-B27 interaction and disease severity
      of syndesmophytes formation in Taiwanese ankylosing spondylitis.
AB  - INTRODUCTION: Ankylosing spondylitis (AS) is a familial, heritable disease
      specified by syndesmophyte formation leading to an ankylosed spine. Endoplasmic
      reticulum aminopeptidase 1 (ERAP1) genetic variations have been widely proved to
      be associated with AS in several ethnic populations. The aim of this study was to
      investigate whether ERAP1 single nucleotide polymorphisms (SNPs) are associated
      with AS susceptibility and disease severity in Taiwanese. METHODS: Four ERAP1
      SNPs (rs27037, rs27980, rs27044 and rs30187) were genotyped in 797 Taiwanese AS
      patients and 1,150 healthy controls. Distributions of genotype and alleles were
      compared between AS patients and healthy controls, and among AS patients
      stratified by clinical parameters. RESULTS: The SNP rs27037T allele appeared to
      be a risk factor for AS susceptibility (P = 5.5 * 10-5, OR 1.30, 95% CI: 1.15 to
      1.48; GT+TT vs. GG P = 9.3 * 10-5, OR 1.49, 95% CI: 1.22 to 1.82). In addition,
      the coding SNP (cSNP) rs27044G allele (P = 1.5 * 10-4, OR 1.28, 95% CI: 1.13 to
      1.46; CG+GG vs. CC, P = 1.7 * 10-3, OR 1.44, 95% CI: 1.15 to 1.81) and the cSNP
      rs30187T allele (P = 1.7 * 10-3, OR 1.23, 95% CI: 1.08 to 1.40; CT+TT vs. CC P =
      6.1 * 10-3, OR 1.38, 95% CI: 1.10 to 1.74) were predisposing factors for AS.
      Notably, the rs27044G allele carriers (CG+GG vs. CC, P = 0.015, OR 1.59, 95% CI:
      1.33 to 2.30) and rs30187T allele carriers (CT+TT vs. CC, P = 0.011, OR 1.63, 95%
      CI: 1.12 to 2.38) were susceptible to syndesmophyte formation in AS patients.
      Furthermore, two cSNPs (rs27044 and rs30187) strongly associated with HLA-B27
      positivity in AS patients. Finally, the ERAP1 SNP haplotype TCG
      (rs27037T/rs27980C/rs27044G) is a major risk factor for AS (adjusted P <0.00001,
      OR 1.38, 95% CI: 1.12 to 1.58) in Taiwanese. CONCLUSIONS: This study provides the
      first evidence of ERAP1 SNPs involving syndesmophyte formation. The interactions
      between ERAP1 SNPs and HLA-B27 play critical roles in pMHC I pathway processing
      contributing to the pathogenesis of AS in multiple populations.

PMID- 22632383
TI  - A survey of the factors associated with concerns about oral antihistamine use in
      Japanese pruritic skin disease patients.
AB  - BACKGROUND: To improve health outcomes during the treatment for pruritic skin
      diseases, it is important to understand which factors most influence patients'
      concerns about oral antihistamine drugs. OBJECTIVES: To survey the nature of
      patients' concerns about oral antihistamine drugs and to examine the factors
      associated with them. METHODS: Patients with pruritic skin diseases expressed
      their concerns regarding the use of oral antihistamine drugs. The independent
      effects of the patients' background characteristics on their concerns were
      examined by multiple logistic regression analysis. RESULTS: A total of 291
      outpatients were completed the study. Overall, 32% of patients were worried about
      using oral antihistamine drugs. The most common concern was about their adverse
      drug events (except drowsiness) and the effects of long-term use. Overall, being
      concerned about antihistamine use was found to be significantly and independently
      associated with a younger age, severe itching, being a homemaker, and having
      previous personal experience of embarrassment due to drowsiness caused by taking
      over-the-counter drugs. CONCLUSIONS: Several factors are associated with altered
      self-reported concerns about antihistamines. Our results suggest the importance
      of understanding the nature of patients' fears about oral antihistamine use so
      that sound advice can be offered to them in a timely manner.

PMID- 22632384
TI  - Adopting and implementing nutrition guidelines in recreational facilities: public
      and private sector roles. A multiple case study.
AB  - BACKGROUND: Recreational facilities are an important community resource for
      health promotion because they provide access to affordable physical activities.
      However, despite their health mandate, many have unhealthy food environments that
      may paradoxically increase the risk of childhood obesity. The Alberta Nutrition
      Guidelines for Children and Youth (ANGCY) are government-initiated, voluntary
      guidelines intended to facilitate children's access to healthy food and beverage
      choices in schools, childcare and recreational facilities, however few
      recreational facilities are using them. METHODS: We used mixed methods within an
      exploratory multiple case study to examine factors that influenced adoption and
      implementation of the ANGCY and the nature of the food environment within three
      cases: an adopter, a semi-adopter and a non-adopter of the ANGCY. Diffusion of
      Innovations theory provided the theoretical platform for the study. Qualitative
      data were generated through interviews, observations, and document reviews, and
      were analysed using directed content analysis. Set theoretic logic was used to
      identify factors that differentiated adopters from the non-adopter. Quantitative
      sales data were also collected, and the quality of the food environment was
      scored using four complementary tools. RESULTS: The keys to adoption and
      implementation of nutrition guidelines in recreational facilities related to the
      managers' nutrition-related knowledge, beliefs and perceptions, as these shaped
      his decisions and actions. The manager, however, could not accomplish adoption
      and implementation alone. Intersectoral linkages with schools and formal, health
      promoting partnerships with industry were also important for adoption and
      implementation to occur. The food environment in facilities that had adopted the
      ANGCY did not appear to be superior to the food environment in facilities that
      had not adopted the ANGCY. CONCLUSIONS: ANGCY uptake may continue to falter under
      the current voluntary approach, as the environmental supports for voluntary
      action are poor. Where ANGCY uptake does occur, changes to the food environment
      may be relatively minor. Stronger government measures may be needed to require
      recreational facilities to improve their food environments and to limit
      availability of unhealthy foods.

PMID- 22632385
TI  - Motivational interviewing and cognitive behaviour therapy for anxiety following
      traumatic brain injury: a pilot randomised controlled trial.
AB  - Although cognitive-behavioural therapy (CBT) is the treatment of choice for
      anxiety, its delivery needs to be adapted for individuals with traumatic brain
      injury (TBI). It also requires clients' active engagement for maximum benefit.
      This study was a pilot randomised controlled trial involving an anxiety treatment
      programme adapted for people with TBI, based on CBT and motivational interviewing
      (MI). Twenty-seven participants with moderate/severe TBI (aged 21-73 years, 78%
      males) recruited from a brain injury rehabilitation hospital were randomly
      allocated to receive MI + CBT (n = 9), non-directive counselling (NDC) + CBT (n =
      10) and treatment-as-usual (TAU) (n = 8). CBT and MI were manualised and
      delivered in 12 weekly individual sessions. Primary outcome was self-reported
      anxiety symptoms assessed at baseline, at the end of NDC/MI and immediately
      following CBT. Assessment was conducted by assessors blinded to group assignment.
      Intention-to-treat analyses showed that the two active treatment groups
      demonstrated significantly greater anxiety reduction than TAU. Participants
      receiving MI showed greater response to CBT, in terms of reduction in anxiety,
      stress and non-productive coping, compared to participants who received NDC. The
      results provided preliminary support for the adapted CBT programme, and the
      potential utility of MI as treatment prelude. Longer follow-up data are required
      to evaluate the maintenance of treatment effects.

PMID- 22632386
TI  - Current dental adhesives systems. A narrative review.
AB  - Adhesive dentistry is based on the development of materials which establish an
      effective bond with the tooth tissues. In this context, adhesive systems have
      attracted considerable research interest in recent years. Successful adhesive
      bonding depends on the chemistry of the adhesive, on appropriate clinical
      handling of the material as well as on the knowledge of the morphological changes
      caused on dental tissue by different bonding procedures. This paper outlines the
      status of contemporary adhesive systems, with particular emphasis on chemical
      characteristics and mode of interaction of the adhesives with enamel and dentinal
      tissues. Dental adhesives are used for several clinical applications and they can
      be classified based on the clinical regimen in "etch-and-rinse adhesives" and
      "self-etch adhesives". Other important considerations concern the different
      anatomical characteristics of enamel and dentine which are involved in the
      bonding procedures that have also implications for the technique used as well as
      for the quality of the bond. Etch-and-rinse adhesive systems generally perform
      better on enamel than self-etching systems which may be more suitable for bonding
      to dentine. In order to avoid a possible loss of the restoration, secondary
      caries or pulp damage due to bacteria penetration or due to cytotoxicity effects
      of eluted adhesive components, careful consideration of several factors is
      essential in selecting the suitable bonding procedure and adhesive system for the
      individual patient situation.

PMID- 22632387
TI  - Medium-term culture of primary oral squamous cell carcinoma in a three-
      dimensional model: effects on cell survival following topical 5-fluororacile
      delivery by drug-loaded matrix tablets.
AB  - Since the activity of several conventional anticancer drugs is restricted by
      resistance mechanisms and dose-limiting side-effects, the design of formulations
      for local application on malignant lesions seems to be an efficient and promising
      drug delivery approach. In this study, the effect of locally applied 5-FU on cell
      death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D
      outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal
      drug dose was established by delivery of solutions containing different amounts
      of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing
      cell death with complete eradication of cell colonies. Buccal tablets were
      designed to deliver 5-FU locoregionally to the cancer lesions of the oral cavity.
      Tablets were prepared using a drug loaded matrix of acrylic/methacrylic acid
      copolymer containing 1% (w/w) of 5-FU and applied on 3D outgrowths. The drug
      release from tablets appeared to be sufficient to induce cell death as confirmed
      by transmission electron microscopy and enzymatic assay (TUNEL). After 120 h of
      treatment, when about 90% of the drug had been discharged from the tablets into
      the culture environment, 5-FU caused loss of cell-cell communications and
      apoptotic cell death. After 192 h, a complete disaggregation of the 3D oral
      outgrowths and the death of all the cells was observed. Buccal matrix tablets
      could be considered a promising new approach to the locoregional treatment of
      OSCC. Risks of systemic toxicity are avoided since very low drug doses are
      delivered.

PMID- 22632388
TI  - Probiotics and oral health.
AB  - Probiotics are living microorganisms (e.g., bacteria) that are either the same as
      or similar to organisms found naturally in the human body and may be beneficial
      to health. Current researches have shown that the balance between beneficial and
      pathogenic bacteria is essential in order to maintain the oral health. Therefore,
      oral cavity has recently been suggested as a relevant target for probiotic
      applications. Dental caries can be seen as a microbial imbalance where the oral
      microbiota shift towards community dominance which produces acidogenic and acid
      tolerant gram positive bacteria. Similarly, the accumulation of bacteria within
      the biofilm, facilitated by poor oral hygiene, predisposes to allogenic shifts in
      the microbial community, leading to the onset of periodontal inflammation.
      Probiotic bacteria belonging to the genus of Lactobacillus, Bifidobacterium and
      Streptococcus have been proven effective for preventing caries by reducing the
      number of cariogenic bacteria in saliva after a short period of consuming the
      probiotic. In contrast, the effect of probiotics on improving gingivitis and
      periodontitis has been less investigated. The currently available studies on the
      effect of probiotics on periodontal pathogens and clinical periodontal parameters
      showed differing results depending on the strains used and the endpoints
      analyzed. Many of the clinical studies are pilot in nature and with low quality,
      therefore, properly conducted clinical trials, using probiotic strains with in
      vitro proven periodontal probiotic effects, are needed. The putative beneficial
      effects of probiotics on oral malodour have also been evaluated, but further
      evidence is needed to fully explore the potential of probiotics for preventing
      malodour.

PMID- 22632389
TI  - Buccal delivery of methimazole as an alternative means for improvement of drug
      bioavailability: permeation studies and matrix system design.
AB  - The aim of this study was to investigate the potential for systemic
      administration of Methimazole (MMI) through the buccal mucosa as an alternative
      route for drug delivery. Considering that the most important restriction in
      buccal drug delivery could be the low permeability of the mucosa, the ability of
      MMI to cross the mucosal barrier was assessed. Permeation of MMI through porcine
      buccal mucosa was investigated ex vivo using Franz type diffusion cells, buffer
      solution simulating saliva or natural human saliva as donor phase. The collected
      data suggested that buccal mucosa does not hinder MMI diffusion and the drug
      crosses the membrane (J(s) = 0.068 mg cm(-2) h(-1) and K(p) = 0.065 cm h(-1)).
      Matrix tablets, suitable for administration on buccal mucosa, were then designed
      and prepared by direct compression of MMI loaded matrices (70% w/w) using
      Eudragit((r)) RS 100 as a matrixing, low permeable, pH-independent, mucoadhesive
      and insoluble agent. The matrix tablets were evaluated in vitro for dissolution;
      however, the drug was discharged too rapidly from tablets. To obtain drug release
      rate suitable to maintain constant drug levels in the central compartment the
      tablets were coated with lipophilic material (glycerol tristearate). In ex vivo
      permeation experiments, therapeutically MMI plasma levels were obtained when
      matrix tablets were coated with 0.10 mm thick lipophilic coating film. Coated
      tablets placed on buccal porcine mucosa provide optimal drug release rate. Coated
      buccal matrix tablets may represent a potential alternative dosage form for
      systemic delivery of MMI in hyperthyroidism management.

PMID- 22632390
TI  - Medium-term culture of normal human oral mucosa: a novel three-dimensional model
      to study the effectiveness of drugs administration.
AB  - Tissue-engineered oral mucosal equivalents have been developed for in vitro
      studies for a few years now. However, the usefulness of currently available
      models is still limited by many factors, mainly the lack of a physiological
      extracellular matrix (ECM) and the use of cell populations that do not reflect
      the properly differentiated cytotypes of the mucosa of the oral cavity. For this
      reason, we have developed a novel three-dimensional culture model reflecting the
      normal architecture of the human oral mucosa, with the main aim of creating a
      better in vitro model where to test cellular responses to drugs administration.
      This novel 3D cell culture model (3D outgrowth) was set up using an artificial
      extracellular matrix (MatrigelTM ), allowing the interactions required for proper
      differentiation of the various citotypes which form the mucosal layer. Biopsies
      of human oral mucosa, in fragments of about 0.5 mm3, were placed onto 6.5mm
      Transwells, covered with MatrigelTM and grown in a specific culture medium. A
      gradual formation of an architectural structure similar to that of the in vivo
      oral mucosa was observed. Transmission electron and confocal microscopy were
      employed to characterize the newly developed model: the cell components
      (keratinocytes and fibroblasts) differentiated properly within the outgrowth and
      reconstituted, in vitro, the physiological structure of the human oral mucosa,
      including a stratified non-keratinized squamous layer composed of four different
      layers, a proper basal membrane and a lamina propria where fibroblasts produce
      ECM. Moreover, keratinocytes expressed CK5, CK13, CK19 and E-cadherin, whereas
      fibroblasts expressed collagen type I and IV, laminin and fibronectin. 3D
      outgrowths could be considered a valid alternative to animal models, and provide
      useful information for researchers interested in studying the responses of the
      human oral mucosa to locally delivered drugs or other exogenous treatments.

PMID- 22632391
TI  - Established and novel approaches for the management of hyposalivation and
      xerostomia.
AB  - Hyposalivation, often symptomatically manifested as xerostomia (dry mouth
      sensation) may indicate the presence of altered salivary gland function and
      places patients at a higher risk for oral complications. Diverse symptoms and
      consequences have been associated with hyposalivation, such as difficulties with
      speaking, swallowing and tasting and a significant increase in dental caries and
      other oral infections. Although hyposalivation may be caused by a variety of
      conditions (head and neck radiotherapy, Sjogren's syndrome, medications, etc.),
      its hallmark symptom, xerostomia, is common to all such disorders, and varies
      only in intensity. Therefore, treatment is generally non-specific, and similar
      therapeutic approaches are used in all cases. In the present paper, available
      palliative oral care in the form of saliva substitutes, such as mouthwashes or
      gels, is detailed. Also salivary flow stimulants, such as certain pharmaceutical
      or gustatory preparations, acupuncture and electrostimulation are reviewed.
      Finally, other approaches, currently under investigation, such as biological and
      gene therapies, are discussed. The degree of evidence of the best known methods
      and their intended use are analyzed.

PMID- 22632392
TI  - Adverse drug reactions in the oral cavity.
AB  - Several drugs may have a number of adverse reactions (ADRs) involving the oro
      facial region. The dose of the drug and the time required for the reaction to
      take place are relevant parameters; nonetheless, ADRs mechanisms are not always
      known and ADRs are not always predictable since aspects other than drug
      pharmacodynamics and/or pharmacokinetics, as well as various interacting
      variables contribute to the final outcome. All tissues and many functions of the
      oral cavity can be affected. In particular, salivary function is frequently
      involved and hypo-salivation is the main manifestation; several mucosal lesions
      with different morphology (ulcerations, vesiculobullous lesions, white lesions,
      pigmentations, swelling) are also possible. Taste, sensation and trigeminal
      function alterations have been reported and the recent evidence regarding the
      occurrence of jawbones osteonecrosis, especially in bisphosphonates treated
      patients, is increasing. Clinical management may be quite difficult due to the
      multiplicity of involved classes of drugs and substances (dental materials,
      foods), the variety of affected tissues and functions, the type of produced
      lesions and disturbances, the complexity of related pathogenetic mechanisms (if
      known), the difficulties in assessing causality and managing drug withdrawal
      and/or dose adjustment, as well as in establishing specific treatments, if any.
      In this paper the most common and significant oral ADRs, their related aspects
      and importance (including medico-legal implications) for health care providers
      will be discussed.

PMID- 22632393
TI  - Oral HPV infection: current strategies for prevention and therapy.
AB  - Infection with High Risk (HR) Human Papillomaviruses (HPVs) is the main
      aetiological agent of Cervical Squamous Cell Carcinoma (CSCC) and also associated
      in a subgroup of other neoplasms, including Oropharyngeal Squamous cell Carcinoma
      (OPSCC). HPV infection, in genital as in oral mucosa, can also be subclinical or
      associated with benign proliferative lesions (common warts, condylomas,
      papillomas) caused mostly by infection with Low Risk (LR)-HPVs. In the last
      decades, extensive research has resulted in growing knowledge on HPV biology and
      specifically viral life cycle, biochemical properties of viral proteins and their
      interaction with the host proteins leading to potential new targets of
      prophylactic or therapeutic vaccines and therapies for HPV infection. In
      addition, notable progresses have been made in the field of diagnostics to detect
      HPV DNA or RNA. The recent epidemiological data suggest the significant changes
      in HPV endemic, due to the changes in sexual habits especially among young
      generations (i.e. early sexual debuts, multiple sexual partners, oral and anal
      sex); this scenario has urged on the need of adequate campaigns of primary
      (sexual education, vaccination programs) and secondary prevention (diagnostics of
      HPV-related diseases). Due to the growing interest on HPV infection and HPV
      related cancers, the authors made a narrative review of the literature on oral
      HPV infection and oral-genital transmission. After this, in view of the
      controversies about the strategies of therapy and prevention of HPV infection,
      the present review focuses on the current state of art about the available tools
      for the therapeutic and, if any, preventive management of oral HPV infection.

PMID- 22632395
TI  - Mucoadhesive polymers for oral transmucosal drug delivery: a review.
AB  - The oral mucosa offers an interesting site for the application of dosage forms
      that release drugs within/throughout the oral mucosa, by assuring a high drug
      bioavailability for topic and systemic effects. However, the relative
      permeability of the oral mucosa and the washing effect related to the oral fluids
      and mechanical stresses must be considered in the formulation of oral dosage
      forms. Since a sustained drug release can be guaranteed only if dosage forms
      remain in contact with the oral site of absorption/application for a prolonged
      time, the development of mucoadhesive dosage forms is mandatory. The mucoadhesion
      is a complex phenomenon and the mucoadhesive bond consists of two different
      parts, the mucoadhesive polymers and the mucous substrate. In addition to factors
      related to the oral mucosa and oral environment features, the physical-chemical
      characteristics of mucoadhesive polymers must be also considered as factors
      influencing the mucoadhesive bonds. While it is not possible to modify the
      mucosal features or it is possible to modify or inhibit only in part certain
      mucosal processes, the knowledge of polymer properties influencing mucoadhesive
      bonds allows to modify or to control these properties in developing increasingly
      effective mucoadhesive systems. The aims of this review are to discuss the
      several mechanisms and factors behind the phenomenon of mucoadhesion with
      particular reference to the features of the oral environment, oral mucosa, and
      polymeric compounds influencing mucoadhesion process. Finally, a brief mention to
      the main mucoadhesive dosage forms designed for oral transmucosal drug delivery
      is made.

PMID- 22632394
TI  - Topical therapies for oral lichen planus management and their efficacy: a
      narrative review.
AB  - Oral Lichen Planus (OLP) is a chronic inflammatory condition implicating T cell
      mediated cytotoxicity, and involving oral mucosal surfaces. Several therapeutic
      regimens have been evaluated to treat OLP and pain related, but often without
      high level of evidence. Topical formulations are the favourite for the majority
      of cases; bioadhesive formulations have been considered very useful and practical
      for local drug delivery in oral mucosa, due to the increased residence time on
      the oral mucosa of the dosage forms and better therapeutic efficacy. In this
      narrative review, authors try to illustrate the current topical managements for
      OLP from the accessible literature on this topic. Steroids are very helpful in
      discomfort and making better quality of life: they are considered the first-line
      treatment even if they could cause secondary candidosis, and sometimes bad taste,
      nausea, dry mouth, sore throat or swollen mouth. Other substances or devices by
      topical administration are adopted especially when the first line approach is
      refractory. This is the case when retinol with its synthetic and natural
      analogues (retinoids), hyaluronic acid, or Aloe Vera are chosen. Recent topical
      applications for OLP therapy include phototherapy and low/high energy pulsing
      light; the treatment with extracorporeal photochemotherapy is also reasonable and
      promising. Finally, calcineurin inhibitors (i.e. cyclosporine, tacrolimus and
      pimecrolimus), antioxidant and biologics (i.e alefacept, efalizumab, basiliximab,
      TNF-alpha inhibitors - infliximab, rituximab) may be alternative approaches when
      OLP does not respond to the standard protocols. In this scenario, there are
      several studies on molecules different from glucocorticosteroids, but not
      sufficient or statistically adequate to justify their evidence-based use in OLP;
      large randomized placebo controlled trials are required to evaluate the safety
      and effectiveness of these non conventional therapies. In conclusion, since OLP
      is a chronic disease and requires long-term management, the dental/medical
      practitioner, who treats OLP patients, needs to know the natural history of OLP,
      how to monitor, and how to treat, taking in account all of the available
      modalities conventional and not, with pros and cons.

PMID- 22632396
TI  - The use of human allogenic graft (HBA) for maxillary bone regeneration: review of
      literature and case reports.
AB  - The use of graft materials is developed from the strong demand to support the
      complete bone regeneration of the empty socket and to increase the bone volume in
      treating the atrophies of sites already consolidated and with adverse alveolar
      bone conditions. A number of graft materials with different origin and mechanism
      of bone regeneration are available. Autologous graft materials, coming from the
      same patient, are defined as the gold-standard. The need of a second surgical
      site and the risk of morbidity and complications may make their use difficult.
      Human bone allografts (HBA) have been recently introduced, in order to offer an
      alternative to the autologous grafts. They have demonstrated to be effective in
      bone regeneration. Recent studies have proved the ability of HBA in bone
      regenerating process as they guarantee a three-dimensional structure for the re
      growth of the new bone and the maintenance of inductive stimuli. In the present
      manuscript, Authors reviewed the evidence supporting the use of HBA in the
      management of the localized ridge atrophies, in the preservation of the extracted
      socket and in the sinus augmentation surgery, and illustrated some original case
      reports.

PMID- 22632397
TI  - Topical fluoride for preventing dental caries in children and adolescents.
AB  - The use of topically applied fluoride has been widely researched as a means to
      reduce the risk of dental caries in conjunction with other treatment modalities
      (mechanical oral hygiene, dietary control, antimicrobial intervention, pit and
      fissure sealants). There is overwhelming evidence that reports not only the
      significance and importance of the use of fluoride as a caries-preventive agent,
      but also how safe fluoride application is when used appropriately, particularly
      in higher risk individuals and populations. This paper reviews the caries
      protective benefits of topical fluoride application in children and adolescents,
      with an emphasis on the clinical efficacy and safety of the vehicles by which
      fluoride is topically delivered. Fluoride toothpaste represents today the most
      cost-effective fluoride-delivery system in the oral cavity and its use should be
      the centerpiece in all caries-preventive strategies. On the other hand,
      mouthrinses, gels and varnishes currently represent adjuncts to toothpaste use
      and should be targeted towards individuals and groups at high risk of caries.

PMID- 22632398
TI  - Innovations in endodontic filling materials: guttapercha vs Resilon.
AB  - One of the goals of endodontic treatment is to achieve a complete,
      tridimensional, hermetic sealing of the root canal system to prevent the entry of
      microorganisms or their products through both the coronal and apical pathways.
      Gutta-percha is the most widely used material for root canal filling and despite
      its numerous properties, such as biocompatibility and thermoplasticity, it has
      however an important limit: the lack of adhesion to the canal walls. Attempts to
      address this problem have been made over the years by using endodontic cements
      capable of bonding to canal dentine but their tendency to resorption in time can
      compromise the quality of treatment. The first step towards a real adhesive
      endodontic filling(4) is rather recent; in fact, it goes back to 2003 when, on
      the occasion of the American Dental Association (ADA) Annual Session, Resilon
      Research LLC introduced a new canal filling adhesive system based on a
      thermoplastic synthetic resin material called ResilonTM. The real innovation of
      this system is its capacity of creating a core made of ResilonTM bonded to the
      cement which adheres to dentine walls previously conditioned with a self-etching
      primer(4) so no changes in the techniques of canal preparation are required. The
      aim of this study was to evaluate the capacity of two filling materials (gutta
      percha and Resilon) to adapt to the canal anatomy, especially on the apical
      third, using the continuous wave of condensation technique. Our data suggest that
      in the third apical the gutta-percha best shows rheological properties that are
      as important as the bond capability.

PMID- 22632399
TI  - Novel non-invasive adjunctive techniques for early oral cancer diagnosis and oral
      lesions examination.
AB  - Oral cancer is a potentially fatal disease with an increasing incidence and an
      unchanged 5-year mortality rate. Unfortunately, oral cancer is often still late
      diagnosed, which leads to an increase in the likelihood of functional impairment
      due to treatment and mortality rate. Definitive diagnosis of oral cancer must be
      confirmed by scalpel biopsy and histological assessment. However despite its
      benefits, scalpel biopsy is invasive and it is burdened by a potential morbidity.
      Furthermore, previous studies have suggested a high degree of intraobserver and
      interobserver variability regarding the histological evaluation of malignancy. As
      a consequence, in recent years there has been a growing and persisting demand
      towards developing new non-invasive, practical diagnostic tools that might
      facilitate the early detection of oral cancer. The most investigated non-invasive
      adjunctive techniques are vital staining, autofluorescence, chemiluminescence,
      narrow band imaging, and exfoliative cytology. Aim of the review is to critically
      describe these adjunctive aids and, after considering the literature data, an
      expert opinion on the effectiveness and the possible use of each technique will
      be provided.

PMID- 22632400
TI  - Synthetic lethality and PARP-inhibitors in oral and head & neck cancer.
AB  - Head and neck cancer refers to a group of malignancies that affects the
      epithelium of the upper aereodigestive tract, primarily the lip and mouth,
      pharynx and larynx. Head and neck cancer is strongly associated with tobacco
      smoking, alcohol consumption and betel nut chewing, and indeed a reduction in the
      exposure to these risk factors has determined a recent decrease in incidence
      rates in many countries. There remains, however, a significant increase in head
      and neck cancer rates in those regions where tobacco epidemic continues, as well
      as in the number of oral cancers related to HPV infection (in particular cancer
      of the oropharynx, tonsil, and base of the tongue), which typically affect young
      adults with no history of exposure to tobacco or alcohol. Treatment of head and
      neck cancer has significantly changed during the last few decades, and an
      increasing number of individuals are currently offered combined chemoradiotherapy
      as single treatment modality for organ preservation or in association with
      surgery to improve prognosis. Unfortunately, the majority of head and neck cancer
      patients eventually succumb to their disease, with inoperable locoregional
      recurrences and lack of response to chemoradiotherapy representing the main
      causes of death. There is an urgent need of novel molecular-targeted therapeutics
      that could overcome the limitations of current treatment modalities. This paper
      reviews the characteristics of a novel group of promising antineoplastic agents,
      poly (ADP-ribose) polymerases (PARP) inhibitors, which cleverly target one of the
      mechanisms cancer cells use to escape the toxic effect of chemoradiation, and
      describe the potential benefits of their addition to current limited range of
      head and neck cancer antineoplastic agents.

PMID- 22632401
TI  - Editorial: Bio-pharmaceutics and materials in oral cavity.

PMID- 22632402
TI  - Activins and inhibins: expression and role in normal and pathological canine
      reproductive organs: a review.
AB  - Activins and inhibins are regulatory proteins of the reproductive function.
      Inhibins antagonise the activin signalling at different levels and are
      responsible for the negative feedback in the regulation of the release of
      pituitary follicle stimulating hormone (FSH), which, in turn, is promoted by
      locally produced activins. In the canine ovary, both peptides are expressed by
      developing follicles and corpora lutea. Activins may play a stimulatory role in
      follicular development, promoting the aromatase function; inhibins modulate these
      processes and suppress the hyperplasic/neoplastic stimuli. Activins are required
      for ovulation and corpus luteum formation, while inhibins stimulate progesterone
      synthesis. The exclusive production of alpha-inhibin by granulosa cells allows
      the peptide to be used as marker to identify canine ovarian stromal tumours by
      immunohistochemistry. In the male, activins are powerful morphogenetic factors in
      the foetal testis. In the adult, they display a modulating action on
      spermatogenesis and Sertoli cell function. Inhibins, produced mainly by Leydig
      cells, promote testosterone secretion. Canine testicular tumours, such as Leydig,
      Sertoli and granulosa cell tumours (GCTs), may express inhibin subunits and
      produce high circulating levels of these glycoproteins. In the canine prostate,
      activins inhibit epithelium proliferation, antagonising androgen effects, but
      they are synthesised under androgenic stimulus.

PMID- 22632403
TI  - The impact of media campaigns on smoking cessation activity: a structural vector
      autoregression analysis.
AB  - AIMS: To evaluate the effect of tobacco control media campaigns and
      pharmaceutical company-funded advertising for nicotine replacement therapy (NRT)
      on smoking cessation activity. DESIGN: Multiple time series analysis using
      structural vector autoregression, January 2002-May 2010. SETTING: England and
      Wales. DATA SOURCES: Tobacco control campaign data from the Central Office of
      Information; commercial NRT campaign data; data on calls to the National Health
      Service (NHS) stop smoking helpline from the Department of Health; point-of-sale
      data on over-the-counter (OTC) sales of NRT; and prescribing data from The Health
      Improvement Network (THIN), a database of UK primary care records. MEASUREMENTS:
      Monthly calls to the NHS stop smoking helpline and monthly rates of OTC sales and
      prescribing of NRT. FINDINGS: A 1% increase in tobacco control television ratings
      (TVRs), a standard measure of advertising exposure, was associated with a
      statistically significant 0.085% increase in calls in the same month (P = 0.007),
      and no statistically significant effect in subsequent months. Tobacco control
      TVRs were not associated with OTC NRT sales or prescribed NRT. NRT advertising
      TVRs had a significant effect on NRT sales which became non-significant in the
      seasonally adjusted model, and no significant effect on prescribing or calls.
      CONCLUSIONS: Tobacco control campaigns appear to be more effective at triggering
      quitting behaviour than pharmaceutical company NRT campaigns. Any effect of such
      campaigns on quitting behaviour seems to be restricted to the month of the
      campaign, suggesting that such campaigns need to be sustained over time.

PMID- 22632404
TI  - Heat exposure induces tissue stress in heat-intolerant, but not heat-tolerant,
      mice.
AB  - We investigated the association of systemic and local tissue stress responses
      with heat-tolerant (TOL) levels in mice. Thirty-eight mice were assigned into
      control and three heat exposure groups-TOL, moderately tolerant, and intolerant
      (INT), based on their overall thermal responses. Real-time core temperature,
      blood pressure, and heart rate (HR) were assessed during heat exposure (39.5 
      degrees C) under conscious condition. Tissue samples were collected 18-22 h
      following heat exposure. INT mice had significantly higher peak mean arterial
      pressure and HR than TOL mice during heat exposure. Plasma corticosterone levels
      were significantly higher in INT than in control mice. No significant changes in
      plasma cytokines or markers of oxidative status were observed. INT mice showed
      significant increases in HSP72 and HSP90 protein and mRNA levels in liver, heart,
      and gastrocnemius muscles compared to TOL and control mice. In contrast, INT mice
      had significantly lower heat shock factor 1 and glucocorticoid receptor protein
      and mRNA levels in these tissues than TOL and control mice. These results
      indicate that acute heat exposure induces stress responses in various tissues of
      INT mice, but not TOL mice. Upregulation of stress proteins by acute heat
      exposure involves both transcriptional and translational pathways.

PMID- 22632405
TI  - Carbon trading for phosphorus gain: the balance between rhizosphere carboxylates
      and arbuscular mycorrhizal symbiosis in plant phosphorus acquisition.
AB  - Two key plant adaptations for phosphorus (P) acquisition are carboxylate
      exudation into the rhizosphere and mycorrhizal symbioses. These target different
      soil P resources, presumably with different plant carbon costs. We examined the
      effect of inoculation with arbuscular mycorrhizal fungi (AMF) on amount of
      rhizosphere carboxylates and plant P uptake for 10 species of low-P adapted
      Kennedia grown for 23 weeks in low-P sand. Inoculation decreased carboxylates in
      some species (up to 50%), decreased plant dry weight (21%) and increased plant P
      content (23%). There was a positive logarithmic relationship between plant P
      content and the amount of rhizosphere citric acid for inoculated and uninoculated
      plants. Causality was indicated by experiments using sand where little citric
      acid was lost from the soil solution over 2 h and citric acid at low
      concentrations desorbed P into the soil solution. Senesced leaf P concentration
      was often low and P-resorption efficiencies reached >90%. In conclusion, we
      propose that mycorrhizally mediated resource partitioning occurred because
      inoculation reduced rhizosphere carboxylates, but increased plant P uptake.
      Hence, presumably, the proportion of plant P acquired from strongly sorbed
      sources decreased with inoculation, while the proportion from labile inorganic P
      increased. Implications for plant fitness under field conditions now require
      investigation.

PMID- 22632406
TI  - Depression and epilepsy: epidemiologic and neurobiologic perspectives that may
      explain their high comorbid occurrence.
AB  - Depression is the most frequent psychiatric comorbidity in people with epilepsy
      (PWE) with lifetime prevalence rates ranging between 30 and 35%. Multifactorial
      variables play a pathogenic role in the high comorbid occurrence of these two
      disorders. These variables were critically examined during an international
      symposium held in Chicago in September 2010, the results of which are presented
      in two companion manuscripts. The first manuscript summarizes new epidemiologic
      data highlighting the bidirectional relation between depression and epilepsy and
      related methodological issues in studying this relationship. An examination of
      the neurobiologic aspects of primary mood disorders, mood disorders in PWE and
      pathogenic mechanisms of epilepsy derived from studies in animal models and
      humans is allowing a better understanding of the complex relation between the two
      conditions. In the first manuscript, we review data from animal models of
      epilepsy in which equivalent symptoms of depression and anxiety disorders develop
      and, conversely, animal models of depression in which the kindling process is
      facilitated. Data from structural and functional neuroimaging studies in humans
      provide a further understanding of potential common pathogenic mechanisms operant
      in depression and epilepsy that may explain their high comorbidity. The negative
      impact of depression on the control of seizure disorders has been documented in
      various studies. In this manuscript, these data are reviewed and potential
      mechanisms explaining this phenomenon are proposed.

PMID- 22632407
TI  - Depression and epilepsy, pain and psychogenic non-epileptic seizures: clinical
      and therapeutic perspectives.
AB  - The clinical manifestations of depression in people with epilepsy (PWE) are
      pleomorphic, often associated with anxiety symptoms and anxiety disorders. The
      ongoing debate of whether the clinical presentation of depression in PWE is
      unique to this neurologic disorder is reviewed. Comorbid depression can impact
      the recruitment of PWE for pharmacologic trials with antiepileptic drugs (AEDs).
      Yet, the impact of depression on the response of the seizure disorder to
      pharmacotherapy with AEDs and its impact on worse adverse events may bias the
      interpretation of the trial findings, particularly when depressed patients are
      included in the AED trials. PWE have a greater suicidal risk than the general
      population. This risk is mediated by multiple factors, and recent data from the
      FDA have imputed a potential pathogenic role to all AEDs. The recognition of
      patients at risk is reviewed. Yet, the validity of the FDA data has been
      questioned, and the status of this controversial question is analyzed. As in the
      case of epilepsy, depression and pain syndromes have a relatively high
      comorbidity. The negative impact of depression on pain is reminiscent of that of
      depression in PWE; furthermore, the high comorbidity may be also associated with
      the existence of common pathogenic mechanisms. Neurologists and in particular,
      epileptologists establish the diagnosis of psychogenic non-epileptic seizures
      (PNES) in whom a comorbid depressive disorder is very often identified. The role
      of depression in the course of PNES and its treatment are discussed. Scarce data
      are available on the treatment of depression in PWE. Thus, clinicians have had to
      adopt data from patients with primary depressive disorders. We outline a
      consensus strategy on the identification and treatment of depressive disorders in
      adult and pediatric patients with epilepsy.

PMID- 22632408
TI  - Characteristic dermoscopic features of primary cutaneous amyloidosis: a study of
      35 cases.
AB  - BACKGROUND: Primary cutaneous amyloidosis (PCA) is a relatively common skin
      disorder among Asians and South Americans. It is usually diagnosed clinically.
      However, for cases with atypical presentations, the diagnosis can be a challenge
      and skin biopsy may be necessary. Dermoscopy has been proved to be a valuable,
      noninvasive tool in the diagnosis of cutaneous pigmented diseases. Most lesions
      of PCA show hyperpigmentation and the major histopathological abnormalities of
      PCA occur in the epidermis and dermal papillae. Dermoscopy might be a powerful
      tool to provide valuable information for the diagnosis of PCA. OBJECTIVES: We
      aimed to find characteristic dermoscopic features of PCA. MATERIALS AND METHODS:
      Cases with typical clinical presentations of PCA, either macular or lichen
      subtypes, were included in this study. All were evaluated using a hand-held,
      polarized and nonpolarized dermoscope. RESULTS: A total of 35 patients with
      clinically diagnosed PCA were enrolled. Eighteen patients had lesions consistent
      with macular amyloidosis and 17 with lichen amyloidosus. We found two major
      dermoscopic patterns characteristic of PCA. The most common dermoscopic finding
      of PCA was a central hub, which could be either white or brown, surrounded by
      various configurations of pigmentation. For cases of lichen amyloidosus with
      prominent hyperkeratosis, the central hub was replaced by a scar-like morphology.
      CONCLUSIONS: This is the first study to report the characteristic dermoscopic
      features of PCA. We demonstrate that the use of a dermoscope may assist in
      achieving an accurate diagnosis of PCA.

PMID- 22632409
TI  - PubMed fever: a disease sweeping medical students?

PMID- 22632410
TI  - Iron(III)-catalyzed Conia-ene cyclization of 2-alkynic 1,3-dicarbonyl compounds.
AB  - A cheap, simple, and effective FeCl(3)-catalyzed Conia-ene cyclization of 2
      alkynic 1,3-dicarbonyl compounds was stereospecific to afford
      alkylidenecyclopentanes in (E)-isomers via the 5-exo-dig pathway. The 5-endo-dig
      and 6-exo-dig cyclizations were also possible, depending on the structure of the
      substrates.

PMID- 22632412
TI  - Genetic characterization of Chikungunya virus from New Delhi reveal emergence of
      a new molecular signature in Indian isolates.
AB  - BACKGROUND: Chikungunya (CHIK) is currently endemic in South and Central India
      and exist as co-infections with dengue in Northern India. In 2010, New Delhi
      witnessed an outbreak of CHIK in the months October-December. This was the first
      incidence of a dominant CHIK outbreak in Delhi and prompted us to characterize
      the Delhi virus strains. We have also investigated the evolution of CHIK spread
      in India. FINDINGS: Clinical samples were subjected to RT-PCR to detect CHIK
      viral RNA. The PCR amplified products were sequenced and the resulting sequences
      were genetically analyzed. Phylogenetic analysis based on partial sequences of
      the structural proteins E1 and E2 revealed that the viruses in the latest
      outbreak exhibited ECSA lineage. Two novel mutations, E1 K211E and E2 V264A were
      observed in all Delhi isolates. In addition, CHIKV sequences from eight states in
      India were analyzed along with Delhi sequences to map the genetic diversity of
      CHIKV within the country. Estimates of average evolutionary divergence within
      states showed varying divergence among the sequences both within the states and
      between the states. We identified distinct molecular signatures of the different
      genotypes of CHIKV revealing emergence of a new signature in the New Delhi clade.
      Statistical analyses and construction of evolutionary path of the virus within
      the country revealed gradual spread of one specific strain all over the country.
      CONCLUSION: This study has identified unique mutations in the E1 and E2 genes and
      has revealed the presence of ancestral CHIKV population with maximum diversity
      circulating in Maharashtra. The study has further revealed the trend of CHIK
      spread in India since its first report in 1963 and its subsequent reappearance in
      2005.

PMID- 22632415
TI  - Parapapillary atrophy in patients with intracranial tumours.
AB  - PURPOSE: To examine size and frequency of parapapillary atrophy (beta zone) in
      patients with intrasellar or perisellar tumours and a glaucoma-like appearance of
      the intrapapillary optic disc region. METHODS: Thirty-four Chinese subjects with
      intrasellar or perisellar tumours and a glaucoma-like appearance of the
      intrapapillary optic disc region and 129 age-matched subjects randomly selected
      from the population-based Beijing Eye Study were enrolled. Beta zone was measured
      on fundus photographs. Size and location of the tumours were assessed on
      neuroradiological images. RESULTS: Beta zone was significantly more common (79 +/
      7% versus 46 +/- 4%; p = 0.001), and it was significantly larger in the tumour
      group than in the control group (circumferential extent: 135 +/- 99 versus 57 +/-
      72; p < 0.001; relative area: 1856 +/- 1923 versus 759 +/- 1390; p = 0.002). The
      width of the intracerebral tumours was significantly associated with the
      circumferential extent of beta zone (r = 0.36, p = 0.039) and with the area of
      beta zone (r = 0.37, p = 0.032). Tumour width, height and depth were
      significantly (p = 0.001; p = 0.012; and p < 0.001, respectively) larger in the
      group of patients with beta zone than in the subgroup of patients without beta
      zone of parapapillary atrophy. CONCLUSIONS: Patients with large intrasellar or
      perisellar tumours and a glaucoma-like appearance of the intrapapillary region as
      compared with a population-based control group had a significantly larger and
      more frequently occurring beta zone of parapapillary atrophy. It suggests that
      large parasellar or suprasellar tumours can be associated with typical
      glaucomatous abnormalities in the parapapillary and intrapapillary region of the
      optic nerve head. It may give hints for the pathogenesis of glaucomatous optic
      neuropathy.

PMID- 22632414
TI  - Emerging drugs for Duchenne muscular dystrophy.
AB  - INTRODUCTION: Duchenne muscular dystrophy (DMD) is the most common, severe
      childhood form of muscular dystrophy. Treatment is limited to glucocorticoids
      that have the benefit of prolonging ambulation by approximately 2 years and
      preventing scoliosis. Finding a more satisfactory treatment should focus on
      maintaining long-term efficacy with a minimal side effect profile. AREAS COVERED:
      Authors discuss different therapeutic strategies that have been used in pre
      clinical and clinical settings. EXPERT OPINION: Multiple treatment approaches
      have emerged. Most attractive are molecular-based therapies that can express the
      missing dystrophin protein (exon skipping or mutation suppression) or a surrogate
      gene product (utrophin). Other approaches include increasing the strength of
      muscles (myostatin inhibitors), reducing muscle fibrosis and decreasing oxidative
      stress. Additional targets include inhibiting NF-kappaB to reduce inflammation or
      promoting skeletal muscle blood flow and muscle contractility using
      phosphodiesterase inhibitors or nitric oxide (NO) donors. The potential for each
      of these treatment strategies to enter clinical trials is a central theme of
      discussion. The review emphasizes that the goal of treatment should be to find a
      product at least as good as glucocorticoids with a lower side effect profile or
      with a significant glucocorticoid sparing effect.

PMID- 22632417
TI  - Ca(2+)  transients in submucous neurons during the colonic migrating motor
      complex in the isolated murine large intestine.
AB  - BACKGROUND: The colonic migrating motor complex (CMMC) is a spontaneous,
      rhythmic, and neurally mediated motor pattern generated by myenteric neurons,
      which can propel fecal pellets in mice. Our aim was to determine whether
      submucous neurons were also activated during the CMMC. METHODS: :The isolated
      murine colon was opened and sections of mucosa were removed to expose the
      submucous ganglia, which were then loaded with Fluo-4. KEY RESULTS: Colonic
      migrating motor complexes, which occurred spontaneously or by mechanically
      stimulating the mucosa, were identified by displacement of the tissue (duration =
      23.3 s). Between CMMCs, spontaneous Ca(2+) transients (frequency = 0.9 Hz) were
      observed in 55% (n = 8) of submucous neurons. During the CMMC, 98% (seven
      ganglia, n = 7) of submucous neurons within the same ganglion exhibited rapid
      Ca(2+) transients (1.6 Hz) superimposed on a sustained rise in Ca(2+) (duration
      ~23 s) that occurred 1.7 s following the mucosal stimulus; whereas other neurons
      exhibited a similar, but delayed response that occurred either at 7 or 13 s
      following the stimulus. The activity in submucous neurons was correlated with
      activity in adjacent nerve varicosities. Ondansetron (1 mm; 5-HT(3) antagonist)
      significantly reduced the frequency and duration of the Ca(2+) transient
      responses. CONCLUSIONS & INFERENCES: Activity in the submucous neurons appears to
      be secondary to that in the myenteric plexus and appears to be generated largely
      by activity in myenteric descending (serotonergic) interneurons. During the CMMC,
      there is likely to be an increase in secretion to lubricate and facilitate fecal
      pellet propulsion.

PMID- 22632416
TI  - Loss of plakoglobin promotes decreased cell-cell contact, increased invasion, and
      breast cancer cell dissemination in vivo.
AB  - INTRODUCTION: The majority of deaths from breast cancer are a result of
      metastases; however, little is understood about the genetic alterations
      underlying their onset. Genetic profiling has identified the adhesion molecule
      plakoglobin as being three-fold reduced in expression in primary breast tumors
      that have metastasized compared with nonmetastatic tumors. In this study, we
      demonstrate a functional role for plakoglobin in the shedding of tumor cells from
      the primary site into the circulation. METHODS: We investigated the effects of
      plakoglobin knockdown on breast cancer cell proliferation, migration, adhesion,
      and invasion in vitro and on tumor growth and intravasation in vivo. MCF7 and
      T47D cells were stably transfected with miRNA sequences targeting the plakoglobin
      gene, or scramble vector. Gene and protein expression was monitored by
      quantitative polymerase chain reaction (qPCR) and Western blot. Cell
      proliferation, adhesion, migration, and invasion were measured by cell counting,
      flow cytometry, and scratch and Boyden Chamber assays. For in vivo experiments,
      plakoglobin knockdown and control cells were inoculated into mammary fat pads of
      mice, and tumor growth, shedding of tumor cells into the bloodstream, and
      evidence of metastatic bone lesions were monitored with caliper measurement, flow
      cytometry, and microcomputed tomography (MUCT), respectively. RESULTS:
      Plakoglobin and gamma-catenin expression were reduced by more than 80% in all
      knockdown cell lines used but were unaltered after transfection with the
      scrambled sequence. Reduced plakoglobin resulted in significantly increased in
      MCF7 and T47D cell proliferation in vitro and in vivo, compared with control,
      with significantly more tumor cells being shed into the bloodstream of mice
      bearing plakoglobin knockdown tumors. In addition, plakoglobin knockdown cells
      showed a >250% increase in invasion through basement membrane and exhibited
      reduced cell-to-cell adhesion compared with control cells. CONCLUSION: Decreased
      plakoglobin expression increases the invasive behavior of breast cancer cells.
      This is the first demonstration of a functional role for plakoglobin/gamma
      catenin in the metastatic process, indicating that this molecule may represent a
      target for antimetastatic therapies.

PMID- 22632418
TI  - Measurements of 13C multiple-quantum coherences in amyloid fibrils under magic
      angle spinning.
AB  - The excitation and detection of high-order multiple quantum coherences among
      (13)C nuclear spins are demonstrated in the samples of [1-(13)C]-L-alanine and
      (13)C labeled amyloid fibrils at a spinning frequency of 20 kHz. The technique is
      based on the double-quantum average Hamiltonian prepared by the DRAMA-XY4 pulse
      sequence. Empirically, we find that multiple supercycles are required to suppress
      the higher-order effects for real applications. Measurements for the fibril
      samples formed by the polypeptides of PrP(113-127) provide the first solid-state
      NMR evidence for the stacking of multiple beta-sheet layers at the structural
      core of amyloid fibrils.

PMID- 22632419
TI  - Natural variability in bovine milk oligosaccharides from Danish Jersey and
      Holstein-Friesian breeds.
AB  - Free oligosaccharides are key components of human milk and play multiple roles in
      the health of the neonate, by stimulating growth of selected beneficial bacteria
      in the gut, participating in development of the brain, and exerting
      antipathogenic activity. However, the concentration of oligosaccharides is low in
      mature bovine milk, normally used for infant formula, compared with both human
      colostrum and mature human milk. Characterization of bovine milk oligosaccharides
      in different breeds is crucial for the identification of viable sources for
      oligosaccharide purification. An improved source of oligosaccharides can lead to
      infant formula with improved oligosaccharide functionality. In the present study
      we have analyzed milk oligosaccharides by high-performance liquid chromatography
      chip quadrupole time-of-flight mass spectrometry and performed a detailed data
      analysis using both univariate and multivariate methods. Both statistical tools
      revealed several differences in oligosaccharide profiles between milk samples
      from the two Danish breeds, Jersey and Holstein-Friesians. Jersey milk contained
      higher relative amounts of both sialylated and the more complex neutral
      fucosylated oligosaccharides, while the Holstein-Friesian milk had higher
      abundance of smaller and simpler neutral oligosaccharides. The statistical
      analyses revealed that Jersey milk contains levels of fucosylated
      oligosaccharides significantly higher than that of Holstein-Friesian milk. Jersey
      milk also possesses oligosaccharides with a higher degree of complexity and
      functional residues (fucose and sialic acid), suggesting it may therefore offer
      advantages in term of a wider array of bioactivities.

PMID- 22632440
TI  - An N = 1 evaluation of enhanced CBT supervision.
AB  - BACKGROUND: Clinical supervision plays an essential role in the development of
      mental health professionals and is increasingly viewed as a discrete professional
      specialization. However, research has rarely addressed core issues such as the
      measurement and manipulation of clinical supervision, so there are very few
      direct comparisons between the different supervision methods. AIMS: To
      operationalize two related approaches, cognitive-behavioural (CBT) and evidence
      based clinical supervision (EBCS), demonstrate their fidelity, and then evaluate
      their relative effectiveness in facilitating the experiential learning of one
      supervisee. METHOD: Within a multiple-baseline, N = 1 design, we rated audiotapes
      of supervision on a competence rating scale. RESULTS: Findings generally favoured
      the EBCS approach, which was associated with higher fidelity by the supervisor
      and increased engagement in experiential learning by the supervisee. CONCLUSIONS:
      This preliminary but novel evaluation indicated that CBT supervision could be
      enhanced. Implications follow for supervisor training and a more rigorous N = 1
      evaluation.

PMID- 22632442
TI  - Reduction rate of body mass index predicts prognosis for survival in amyotrophic
      lateral sclerosis: a multicenter study in Japan.
AB  - Malnutrition in the early stage has been reported as an independent predictor of
      survival in amyotrophic lateral sclerosis (ALS). We analyzed retrospectively the
      effect of variation of body mass index (BMI) on survival in ALS patients. In
      total, 77 consecutive ALS patients were enrolled from nine hospitals in Japan.
      Reduction rate of BMI was calculated from BMI before the disease onset and at the
      time of the first visit to each hospital. We analyzed the correlation between BMI
      reduction rate and total disease duration. Results showed that the median BMI
      reduction rate was 2.5 per year (interquartile range 1.3-3.8). The BMI reduction
      rate was significantly correlated with survival length (p <0.0001). There was
      also a significant difference in survival between ALS patients with a BMI
      reduction rate >= and < 2.5 (Kaplan-Meier survival analysis and the log-rank
      test, p < 0.0001; hazard ratio by the Cox model, 2.9816). In conclusion, faster
      reduction of BMI at the initial stage before the first visit to hospital predicts
      shorter survival length also in Japanese ALS patients.

PMID- 22632441
TI  - An increase in ALS incidence on the Kii Peninsula, 1960-2009: a possible link to
      change in drinking water source.
AB  - We investigated changes in the incidence of amyotrophic lateral sclerosis (ALS)
      in the Koza/Kozagawa/Kushimoto area (K. area) in the Kii Peninsula, Japan in 1960
      2009. Probable and definite ALS cases diagnosed using El Escorial criteria were
      collected during a five-decade period: period I-V, 1960-2009. Forty-three ALS
      patients matched the selection criteria in the overall K. area, including three
      patients on Oshima, a small island opposite the mainland K. area. The age- and
      gender-adjusted incidence of ALS in the overall K. area (standardized for the
      2005 Japanese population) decreased from 5.47/100,000 (95% CI 1.86-9.08) in
      period I to 0.61/100,000 (95% CI-0.28-1.50) in period III, and then increased to
      4.39/100,000 (95% CI 1.70-7.07) in period V. On Oshima, the age- and gender
      adjusted incidence of ALS was 9.45/100,000 (95% CI-7.39-26.29) in period V. The
      present research indicates an increase of ALS incidence in the K. area,
      especially on Oshima. A limitation of this study was the small population.

PMID- 22632443
TI  - Impaired proteasome function in sporadic amyotrophic lateral sclerosis.
AB  - Abstract   The ubiquitin-proteasome system, important for maintaining protein
      quality control, is compromised in experimental models of familial ALS. The
      objective of this study was to determine if proteasome function is impaired in
      sporadic ALS. Proteasomal activities and subunit composition were evaluated in
      homogenates of spinal cord samples obtained at autopsy from sporadic ALS and non
      neurological control cases, compared to cerebellum as a clinically spared tissue.
      The level of 20S alpha structural proteasome subunits was assessed in motor
      neurons by immunohistochemistry. Catalysis of peptide substrates of the three
      major proteasomal activities was substantially reduced in ALS thoracic spinal
      cord, but not in cerebellum, accompanied by alterations in the constitutive
      proteasome machinery. Chymotrypsin-like activity was decreased to 60% and 65% of
      control in ventral and dorsal spinal cord, respectively, concomitant with
      reduction in the beta5 subunit with this catalytic activity. Caspase- and trypsin
      like activities were reduced to a similar extent (46% - 68% of control).
      Proteasome levels, although generally maintained, appeared reduced specifically
      in motor neurons by immunolabelling. In conclusion, there are commonalities of
      findings in sporadic ALS patients and presymptomatic SOD1-G93A transgenic mice
      and these implicate inadequate proteasome function in the pathogenesis of both
      familial and sporadic ALS.

PMID- 22632444
TI  - An ALS case with a novel D90N-SOD1 heterozygous missense mutation.
AB  - Abstract   Amyotrophic lateral sclerosis (ALS) is the most common form of motor
      neuron disease. We describe the case of a patient with a rapidly progressive form
      of ALS characterized by both upper and lower motor neuron impairment, no early
      bulbar signs and severe pain in all four extremities. The patient had a
      heterozygous c.271G > A mutation in SOD1, leading to an amino acids substitution
      of asparagine to aspartate at position 90 of the protein chain (p.D90N). Our
      report confirms that ALS patients with D90 codon heterozygous mutations may be
      associated with rapid progression and a prominent pain syndrome.

PMID- 22632445
TI  - T137A variant is a pathogenetic SOD1 mutation associated with a slowly
      progressive ALS phenotype.

PMID- 22632446
TI  - ALSUntangled No. 16: cannabis.

PMID- 22632449
TI  - Carbon nanotube quantum dots as highly sensitive terahertz-cooled spectrometers.
AB  - Terahertz technology has recently emerged as a highly sought-after and versatile
      scientific tool in many fields, including medical imaging, security screening,
      and wireless communication. However, scientific progress has been hindered by the
      lack of sources and detectors in this frequency range, thereby known as the
      terahertz gap. Here, we show that carbon nanotube quantum dots coupled to
      antennas are extremely sensitive, broad-band, terahertz quantum detectors with
      spectral resolution. Their response is due to photon-assisted single-electron
      tunneling and it is substantially enhanced by a novel radiation-induced
      nonequilibrium cooling of the electrons, causing a sharp height increase of the
      Coulomb oscillation peaks.

PMID- 22632448
TI  - Intra-operative transanal near infrared imaging of colorectal anastomotic
      perfusion: a feasibility study.
AB  - AIM: Anastomotic dehiscence is a devastating complication. Inadequate blood
      supply is felt to be the prevailing cause. This study describes the use of near
      infrared imaging to evaluate transanally anastomotic tissue perfusion following
      low anterior resection. METHOD: Twenty patients undergoing low anterior resection
      for benign and malignant disease were studied. After completing the anastomosis,
      indocyanine green (ICG) was injected via a peripheral intravenous catheter. An
      endoscopic near infrared imaging system (Pinpoint, Novadaq, Canada) was then used
      transanally to visualize mucosal perfusion of the colon, rectum and the
      anastomotic staple line. RESULTS: All patients underwent a technically successful
      ICG angiogram. The angiogram was abnormal in four patients. Two of these had a
      protective loop ileostomy and showed no sign of anastomotic breakdown. The other
      two patients were found on CT scan to have a peri-anastomotic collection
      consistent with anastomotic leakage. Both were managed conservatively with
      resolution. CONCLUSION: This study confirms that transanal ICG angiography is
      feasible and provides imaging of mucosal and anastomotic blood flow. The
      technique warrants further study in a larger group of patients to assess its
      ability to identify defects in tissue perfusion that may lead to anastomotic
      breakdown.

PMID- 22632450
TI  - Development of a motivational interviewing programme as a prelude to CBT for
      anxiety following traumatic brain injury.
AB  - A brief preparatory programme, based on the principles of motivational
      interviewing (MI), was developed as a way of engaging clients with traumatic
      brain injury (TBI) and preparing them for a cognitive behaviour therapy (CBT)
      programme for anxiety. The MI + CBT programme was delivered to a male client in
      his early 40s with severe TBI at four months post-injury, using a single-subject
      design with repeated measures pre- and post-treatment. The client received three
      sessions of manualised MI, followed by nine sessions of CBT. The MI sessions
      focused on helping the client to develop more realistic goals and supporting his
      self-efficacy about his ability to cope with anxiety. Specific strategies were
      used to accommodate the client's cognitive limitations, such as the use of
      personally meaningful metaphors and role plays. Re-assessments were conducted at
      the end of MI, CBT and nine weeks post-treatment, using a semi-structured
      clinical interview and self-report measures of anxiety, mood and change
      expectancy. The client showed significant improvement in anxiety following
      treatment and a significant reduction in subjective units of distress (SUDS)
      between the MI and CBT phases. The results suggest the potential utility of MI in
      people with TBI, and the need to evaluate treatment protocols in a controlled
      trial.

PMID- 22632451
TI  - Cost-efficacy comparison of biological therapies for patients with moderate to
      severe psoriasis in Japan.
AB  - BACKGROUND: Biological therapies have recently been introduced for patients with
      moderate to severe psoriasis in Japan. OBJECTIVES: This research aims to assess
      the cost efficacy of adalimumab, infliximab and ustekinumab treatments for
      psoriasis in a Japanese environment. METHODS: A mixed-treatment comparison was
      performed to estimate the comparative efficacy of biological therapies using
      Psoriasis Area and Severity Index (PASI) scores based on data from randomized,
      double-blind, controlled studies. Costs included only the drug costs calculated
      by the approved dosing and schedule. Cost efficacy was determined by dividing the
      cost by the probability of achieving a PASI 75 response. RESULTS: Infliximab had
      the highest probability of a PASI 75 response (83%), followed by ustekinumab 45
      mg (74%) and adalimumab (59%). Infliximab was the most expensive biologic,
      whereas the costs of ustekinumab 45 mg and adalimumab were similar. In the first
      year of induction treatment, the lowest cost per responder was for ustekinumab 45
      mg, followed by adalimumab and infliximab. In the subsequent year of maintenance
      treatment, the cost per responder of ustekinumab 45 mg remained the lowest while
      infliximab and adalimumab had similar cost efficacy. CONCLUSIONS: Ustekinumab was
      a more cost-efficient biological therapy than adalimumab or infliximab for
      psoriasis patients in a Japanese setting.

PMID- 22632452
TI  - Evaluation of vulvovaginal symptoms and Candida colonization in women with type 2
      diabetes mellitus treated with canagliflozin, a sodium glucose co-transporter 2
      inhibitor.
AB  - BACKGROUND/OBJECTIVE: Women with type 2 diabetes mellitus (T2DM) are at increased
      risk for vaginal Candida colonization, perhaps because of glucosuria. Sodium
      glucose co-transporter 2 (SGLT2) inhibitors, in development for the treatment of
      T2DM, improve glycemic control by increasing urinary glucose excretion. Vaginal
      Candida colonization and symptomatic vulvovaginal adverse events (VVAE) were
      assessed in females with T2DM treated with canagliflozin, a SGLT2 inhibitor.
      METHODS: In a double-blind study, subjects with T2DM and inadequate glycemic
      control on metformin were randomized to placebo; canagliflozin 50, 100, 200, 300
      mg daily or 300 mg twice daily; or sitagliptin 100 mg daily for 12 weeks. Vaginal
      swabs for Candida culture were collected from 198 female subjects at baseline and
      week 12, and during the trial if symptoms consistent with vulvovaginal
      candidiasis occurred. RESULTS: At baseline, 23/198 (12%) females had vaginal
      cultures positive for Candida (C. glabrata: 14; C. albicans: 5; other: 4), with
      age <=55 years associated with increased risk (odds ratio [OR], 3.5; 95%
      confidence interval [CI], 1.1-10.7). Of those with negative cultures at baseline,
      31% of canagliflozin and 14% of placebo/sitagliptin subjects converted to
      positive at week 12 (OR, 2.8; 95% CI, 1.0-7.3 for canagliflozin vs.
      placebo/sitagliptin). Two placebo/sitagliptin (3%) and 16 canagliflozin subjects
      (10%) experienced VVAE. Positive vaginal culture for Candida species at baseline
      was a risk factor for VVAE (OR, 9.1; 95% CI, 2.4-34.0). All 9/9 subjects in the
      canagliflozin group with a vaginal culture taken at the time of the VVAE were
      positive for Candida species. Most VVAE were treated with antifungal therapy and
      resolved without study drug interruption; none led to discontinuation. Study
      limitations include small population, short duration, and not obtaining cultures
      in all women with VVAE. CONCLUSION: Canagliflozin treatment was associated with
      an increase in vaginal colonization with Candida species and in VVAE in women
      with T2DM.

PMID- 22632455
TI  - Risk factors for drug-resistant Streptococcus pneumoniae and antibiotic
      prescribing practices in outpatient community-acquired pneumonia.
AB  - OBJECTIVES: Due to antimicrobial resistance in Streptococcus pneumoniae, national
      guidelines recommend a respiratory fluoroquinolone or combination antimicrobial
      therapy for outpatient treatment of community-acquired pneumonia (CAP) associated
      with risk factors for drug-resistant S. pneumoniae (DRSP). The objectives of this
      study were to assess the prevalence of these risk factors and antibiotic
      prescribing practices in cases of outpatient CAP treated in the acute care
      setting. METHODS: This was a retrospective cohort study of adult outpatients
      treated for CAP in the emergency department (ED) or urgent care center of an
      urban, academic medical center from May 1, 2009, through October 31, 2009, and
      comparison of antibiotic therapy in cases with and without DRSP risk factors.
      RESULTS: Of 175 patients, 90 (51%) had at least one DRSP risk factor, most
      commonly asthma (n = 28, 16%), alcohol abuse (n = 24, 14%), diabetes mellitus (n
      = 18, 10%), chronic obstructive pulmonary disease (n = 16, 9%), age > 65 years (n
      = 16, 9%), and use of antibiotics within 3 months (15, 9%). Antibiotic
      prescriptions were similar among cases with and without DRSP risk factors: a
      macrolide (62% vs. 59%, respectively, p = 0.65), doxycycline (27% vs. 28%, p =
      0.82), or a respiratory fluoroquinolone (9% vs. 9%, p = 0.90). Concordance with
      national guideline treatment recommendations was significantly lower in cases
      with DRSP risk factors (9% vs. 87%, p < 0.0001). CONCLUSIONS: DRSP risk factors
      were present in approximately half of outpatient CAP cases treated in the acute
      care setting; however, guideline-concordant antibiotic therapy was infrequent.
      Strict adherence to current guidelines would substantially increase use of
      fluoroquinolones or combination therapy. Whether the potential risks associated
      with these broad-spectrum regimens are justified by improved clinical outcomes
      requires further study.

PMID- 22632453
TI  - Serotonin of mast cell origin contributes to hippocampal function.
AB  - In the central nervous system, serotonin, an important neurotransmitter and
      trophic factor, is synthesized by both mast cells and neurons. Mast cells, like
      other immune cells, are born in the bone marrow and migrate to many tissues. We
      show that they are resident in the mouse brain throughout development and
      adulthood. Measurements based on capillary electrophoresis with native
      fluorescence detection indicate that a significant contribution of serotonin to
      the hippocampal milieu is associated with mast cell activation. Compared with
      their littermates, mast cell-deficient C57BL/6 Kit(W-sh/W-sh)  mice have profound
      deficits in hippocampus-dependent spatial learning and memory and in hippocampal
      neurogenesis. These deficits are associated with a reduction in cell
      proliferation and in immature neurons in the dentate gyrus, but not in the
      subventricular zone - a neurogenic niche lacking mast cells. Chronic treatment
      with fluoxetine, a selective serotonin reuptake inhibitor, reverses the deficit
      in hippocampal neurogenesis in mast cell-deficient mice. In summary, the present
      study demonstrates that mast cells are a source of serotonin, that mast cell
      deficient C57BL/6 Kit(W-sh/W-sh)  mice have disrupted hippocampus-dependent
      behavior and neurogenesis, and that elevating serotonin in these mice, by
      treatment with fluoxetine, reverses these deficits. We conclude that mast cells
      contribute to behavioral and physiological functions of the hippocampus and note
      that they play a physiological role in neuroimmune interactions, even in the
      absence of inflammatory responses.

PMID- 22632456
TI  - Comparison between a novel bovine xenoimplant and autogenous cancellous bone
      graft in tibial tuberosity advancement.
AB  - OBJECTIVE: To compare radiographic healing and clinical outcome of a frontal
      opening wedge osteotomy of canine tibiae when the osteotomy site is packed with
      either a novel bovine xenograft or standard autogenous cancellous bone graft
      (ACBG). STUDY DESIGN: Cohort study. ANIMALS: Dogs (n = 82) with partial or
      complete rupture of the cranial cruciate ligament that had tibial tuberosity
      advancement (TTA). METHODS: In 48 dogs, the osteotomy was packed with a novel
      bovine xenograft and in 34 dogs, ACBG was used. Eight week postoperative
      radiographs from both groups were graded for osteotomy healing using a 0-4-point
      scale. Data were analyzed using a Mann-Whitney test with significance set at P <
      .05. RESULTS: Thirty-four dogs (39 stifles) with xenoimplants had complete
      records and radiographic follow-up at 8 weeks. No significant differences between
      xenografting and autografting were identified in grading of osteotomy fill,
      osteointegration, or healing of the distal osteotomy. Significant differences
      were noted in grading of osteotomy healing proximally (autograft > xenoimplant)
      and of opacity in the osteotomy site (xenoimplant > autograft). CONCLUSIONS:
      Radiographic evidence of healing of the xenoimplanted portion of the TTA
      osteotomy was equivalent to results with ACBG. Healing of the proximal osteotomy
      site (above the cage) was improved when ACBG was used as the graft.

PMID- 22632457
TI  - Nanoparticles from photocopiers induce oxidative stress and upper respiratory
      tract inflammation in healthy volunteers.
AB  - Photocopiers emit large quantities of nanoparticles (NPs); however, their
      toxicological properties have not been studied. Here we investigate for the first
      time early human responses following a day's exposure to NPs from photocopiers.
      Nine healthy subjects spent 6 h at a busy photocopy centre on 2-3 randomly
      selected days. Matched nasal lavage and urine samples were collected before and
      at different time points post-exposure. Nasal lavage samples were analysed for 14
      cytokines, inflammatory cells and total protein. Urine samples were analysed for
      8-hydroxydeoxyguanosine (8-OH-dG). Exposure assessment was conducted using a
      suite of instruments. The mean total particle number on exposure days was >5
      times higher than background, with size distributions in nanoscale range (peak 30
      40 nm). Following exposure, 8-OH-dG and several pro-inflammatory cytokines were
      elevated 2-10 folds compared with pre-exposure levels and remained elevated for
      up to 36 h. We conclude that NPs from photocopiers induce upper airway
      inflammation and oxidative stress.

PMID- 22632458
TI  - Gambling, housing conditions, community contexts and child health in remote
      indigenous communities in the Northern Territory, Australia.
AB  - BACKGROUND: Recent government reports have identified gambling, along with
      alcohol abuse, drug abuse and pornography, as contributing to child neglect and
      abuse in Indigenous communities in the Northern Territory (NT). These reports
      also identify gaps in empirical evidence upon which to base sound policy. To
      address this shortfall, data from ten remote Indigenous communities was analysed
      to determine the relationship between gambling problems, housing conditions,
      community contexts and child health in indigenous communities. METHODS: Logistic
      regression was used to assess associations between gambling problems, community
      contexts, housing conditions and child health. Separate multivariable models were
      developed for carer reported gambling problems in houses and six child health
      outcomes. RESULTS: Carer reported gambling problems in households across the ten
      communities ranged from 10% to 74%. Inland tropical communities had the highest
      level of reported gambling problems. Less access to a doctor in the community
      showed evidence of a multivariable adjusted association with gambling problems in
      houses. No housing variables showed evidence for a multivariable association with
      reported gambling problems. There was evidence for gambling problems having a
      multivariable adjusted association with carer report of scabies and ear infection
      in children. CONCLUSIONS: The analyses provide evidence that gambling is a
      significant problem in Indigenous communities and that gambling problems in
      households is related to poor child health outcomes. A comprehensive (prevention,
      treatment, regulation and education) public health approach to harm minimisation
      associated with gambling amongst the Indigenous population is required that
      builds on current normative community regulation of gambling.

PMID- 22632459
TI  - Natural transmission of feline immunodeficiency virus from infected queen to
      kitten.
AB  - BACKGROUND: Feline immunodeficiency virus (FIV) is a naturally occurring
      lentivirus that infects cats. The primary mode of transmission occurs through
      bite wounds, and other routes are difficult to observe in nature. FINDINGS: The
      purpose of this study was to evaluate FIV transmission from queen to kitten in a
      colony of naturally infected stray cats. With this aim, a queen was monitored
      over a period of three years. A blood sample was taken to amplify and sequence
      gag, pol and env regions of the virus from the queen, two kittens and other cats
      from the colony. CONCLUSION: Phylogenetic analysis showed evidence of queen to
      kitten transmission.

PMID- 22632460
TI  - Prognostic factors in vitrectomy for lamellar macular hole assessed by spectral
      domain optical coherence tomography.
AB  - PURPOSE: To evaluate the association between the macular structure on spectral
      domain optical coherence tomography (SD-CT) and visual outcome after vitrectomy
      for lamellar macular hole (LMH). METHODS: Best-corrected visual acuity (VA) and
      SD-OCT images of the macula were assessed before and after surgery in 30 eyes of
      30 patients with a LMH. Preoperative VA and SD-OCT features were investigated as
      predictors of surgical outcome. RESULTS: Mean patient age was 65 years with
      female predominance (77%). Visual acuity improved in 19 eyes (63%) with an
      overall mean improvement of 1 Snellen line (from 20/65 to 20/50; p = 0.002) at a
      mean of 18 months after vitrectomy. Subgroup analysis showed that statistically
      significant visual benefit was only observed in patients with an intact
      photoreceptor inner segment/outer segment (IS/OS) junction (p = 0.003), with
      foveal thickness bigger than 100 MUm (p = 0.004) and with initial VA better than
      20/100 (p = 0.003). The most efficient model to predict final VA was the
      combination of preoperative VA and the presence or absence of IS/OS disruption
      (r(2) = 0.77, p < 0.001). CONCLUSIONS: Poor initial VA, the presence of a
      disrupted IS/OS junction or a thin fovea on preoperative SD-OCT predicted poor
      vision outcome after LMH surgery.

PMID- 22632461
TI  - On the biomechanics of stem cell niche formation in the gut--modelling growing
      organoids.
AB  - In vitro culture of intestinal tissue has been attempted for decades. Only
      recently did Sato et al. [Sato, T., Vries, R. G., Snippert, H. J., van de
      Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P.,
      Peters, P. J., et al. (2009) Nature 459, 262-265] succeed in establishing long
      term intestinal culture, demonstrating that cells expressing the Lgr5 gene can
      give rise to organoids with crypt-like domains similar to those found in vivo. In
      these cultures, Paneth cells provide essential signals supporting stem cell
      function. We have recently developed an individual cell-based computational model
      of the intestinal tissue [Buske, P., Galle, J., Barker, N., Aust, G., Clevers, H.
      & Loeffler, M. (2011) PLoS Comput Biol 7, e1001045]. The model is capable of
      quantitatively reproducing a comprehensive set of experimental data on intestinal
      cell organization. Here, we present a significant extension of this model that
      allows simulation of intestinal organoid formation in silico. For this purpose,
      we introduce a flexible basal membrane that assigns a bending modulus to the
      organoid surface. This membrane may be re-organized by cells attached to it
      depending on their differentiation status. Accordingly, the morphology of the
      epithelium is self-organized. We hypothesize that local tissue curvature is a key
      regulatory factor in stem cell organization in the intestinal tissue by
      controlling Paneth cell specification. In simulation studies, our model closely
      resembles the spatio-temporal organization of intestinal organoids. According to
      our results, proliferation-induced shape fluctuations are sufficient to induce
      crypt-like domains, and spontaneous tissue curvature induced by Paneth cells can
      control cell number ratios. Thus, stem cell expansion in an organoid depends
      sensitively on its biomechanics. We suggest a number of experiments that will
      enable new insights into mechano-transduction in the intestine, and suggest model
      extensions in the field of gland formation.

PMID- 22632463
TI  - Origin and modulation of circular smooth muscle layer contractions in the porcine
      esophagus.
AB  - BACKGROUND: The origin and modulation mechanisms controlling timing and amplitude
      of esophageal body peristalsis are not fully understood. We aimed to characterize
      the neurotransmitters involved in the origin and modulation of circular smooth
      muscle esophageal body (EB) contractions. METHODS: Responses of porcine EB strips
      to electrical stimulation of motor neurons (MNs) were assessed in organ baths and
      with microelectrodes. The effect of antagonists of inhibitory (L-NAME 1 mmol L(
      1) , MRS2179 10 MUmol L(-1) ) and excitatory neurotransmitters (atropine 1 MUmol
      L(-1) ; SR140333 1 MUmol L(-1) -NK(1) ra-, GR94800 1 MUmol L(-1) -NK(2) ra-) and
      of ganglionic neurotransmitters (hexamethonium 100 MUmol L(-1) , ondansetron 1
      MUmol L(-1) , NF279 10 MUmol L(-1) ) were characterized. KEY RESULTS: Electrical
      field stimulation (EFS) induced a frequency-dependent off-contraction (16.8 +/-
      0.8 g) following a latency period. Latency was significantly reduced by L-NAME (
      66.1 +/- 4.1%) and MRS2179 (-25.9 +/- 5.6%), and strongly increased by atropine
      (+36.8 +/- 5.8%). Amplitude was reduced by L-NAME (-69.9 +/- 10.4%), MRS2179 (
      34.1 +/- 6.0%), atropine (-42.3 +/- 4.7%), hexamethonium (-18.9 +/- 3.3%), NF279
      (-20.7 +/- 3.5%), ondansetron (-16.3 +/- 3.2%), GR94800 (-28.0 +/- 4.8%) SR140333
      (-20.9 +/- 7.1%), and alpha-chymotrypsin (-31.3 +/- 7.0%). The EFS induced a
      monophasic nitrergic inhibitory junction potential. CONCLUSIONS & INFERENCES: Our
      results suggest that timing (latency) and amplitude of esophageal contractions
      are determined by a balance of complex interactions between excitatory and
      inhibitory MNs. Latency depends on the activation of inhibitory MNs releasing NO
      and a minor purinergic contribution through P2Y(1) receptors, and excitatory MNs
      releasing ACh. Amplitude depends on a major contribution of excitatory MNs
      releasing ACh and tachykinins, and also on inhibitory MNs releasing NO, ATP or
      related purines, and peptidergic neurotransmitters acting as strong modulators of
      the excitatory neuroeffector transmission.

PMID- 22632462
TI  - Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by
      hybrid minigenes.
AB  - INTRODUCTION: The underlying pathogenic mechanism of a large fraction of DNA
      variants of disease-causing genes is the disruption of the splicing process. We
      aimed to investigate the effect on splicing of the BRCA2 variants c.8488-1G > A
      (exon 20) and c.9026_9030del (exon 23), as well as 41 BRCA2 variants reported in
      the Breast Cancer Information Core (BIC) mutation database. METHODS: DNA variants
      were analyzed with the splicing prediction programs NNSPLICE and Human Splicing
      Finder. Functional analyses of candidate variants were performed by lymphocyte RT
      PCR and/or hybrid minigene assays. Forty-one BIC variants of exons 19, 20, 23 and
      24 were bioinformatically selected and generated by PCR-mutagenesis of the wild
      type minigenes. RESULTS: Lymphocyte RT-PCR of c.8488-1G > A showed intron 19
      retention and a 12-nucleotide deletion in exon 20, whereas c.9026_9030del did not
      show any splicing anomaly. Minigene analysis of c.8488-1G > A displayed the
      aforementioned aberrant isoforms but also exon 20 skipping. We further evaluated
      the splicing outcomes of 41 variants of four BRCA2 exons by minigene analysis.
      Eighteen variants presented splicing aberrations. Most variants (78.9%) disrupted
      the natural splice sites, whereas four altered putative enhancers/silencers and
      had a weak effect. Fluorescent RT-PCR of minigenes accurately detected 14 RNA
      isoforms generated by cryptic site usage, exon skipping and intron retention
      events. Fourteen variants showed total splicing disruptions and were predicted to
      truncate or eliminate essential domains of BRCA2. CONCLUSIONS: A relevant
      proportion of BRCA2 variants are correlated with splicing disruptions, indicating
      that RNA analysis is a valuable tool to assess the pathogenicity of a particular
      DNA change. The minigene system is a straightforward and robust approach to
      detect variants with an impact on splicing and contributes to a better knowledge
      of this gene expression step.

PMID- 22632464
TI  - Susceptibility of different mice strains to okadaic acid, a diarrhetic shellfish
      poisoning toxin.
AB  - The mouse bioassay is widely used to detect diarrhetic shellfish poisoning (DSP)
      toxins. To the best of our knowledge, however, there have been no reports
      specifically on strain differences in susceptibility to DSP toxins. In this
      study, we investigated the susceptibility of different mice strains to okadaic
      acid (OA), one of the representative DSP toxins. A lethal dose of OA was injected
      intraperitoneally (i.p.) into mice. The mice were observed until 24 h after
      injection. Five inbred strains (A/J, BALB/c, C3H/He, C57BL/6, and DBA/2) and two
      non-inbred strains (ddY, and ICR) of mice were compared. All the mice were male,
      weighed 16-20 g, and were 4-5 weeks old. The lethality was 90-100% in the A/J,
      BALB/c, ddY, and ICR strains, 70-80% in the C3H/He and C57BL/6 strains, and 40%
      in DBA/2 strain. Survival analysis showed that the BALB/c, C57BL/6, ddY, and ICR
      strains died earlier and the A/J, C3H/He and DBA/2 strains survived longer. These
      results indicate that significant differences may exist in the susceptibility of
      mice strains to OA.

PMID- 22632465
TI  - Metastatic melanoma: results of 'classical' second-line treatment with cytotoxic
      chemotherapies.
AB  - BACKGROUND: Metastatic melanoma is one of the most aggressive tumours, with a
      median survival that does not exceed 12 months. None of the cytotoxic first-line
      therapies have shown survival benefit in randomised clinical trials. OBJECTIVE:
      To describe clinical benefit of second-line cytotoxic chemotherapy in the second
      line of treatment for metastatic melanoma. METHODS: In a retrospective study, we
      analyse the outcome of patients with metastatic melanoma who had received two
      lines or more of cytotoxic treatments in four French dermato-oncology departments
      between 1999 and 2009. RESULTS: We describe the outcomes for 109 patients. Most
      of these patients received dacarbazine for the first line of chemotherapy and
      fotemustine for the second line of chemotherapy (67.0 and 64.2%, respectively). A
      clinical benefit was observed in 24.1% of the patients and overall survival was
      4.1 months after the second-line treatment. At least 23.8% of patients suffered
      from grade 3 or 4 toxicities. The presence of more than two sites of metastasis
      and an M1c staging according to the AJCC classification represented negative
      predictive factors of clinical benefit. CONCLUSION: This study shows the modest
      benefit of a second line of cytotoxic chemotherapy in a nonselected population.
      If eligible, these patients should be proposed for ongoing clinical trials or for
      targeted therapies.

PMID- 22632466
TI  - Antibacterial action of new antibacterial peptides, Nod1 and Nod2, isolated from
      Nordotis discus discus.
AB  - Abalone is a valuable seafood in the aquaculture industry worldwide as it is rich
      in protein. However, to date, research on the functional proteins of abalone is
      lacking. Herein, we report two peptides with antibacterial activity from Nordotis
      discus discus . The purification of peptides was performed by solvent extraction,
      ultrafiltration, and reverse-phase high performance liquid chromatography. The N
      terminal amino acid sequences of the isolated antibacterial peptides, named as
      Nod1 and Nod2, were identified by Edman degradation and did not show any
      similarity to other proteins and peptides in databases based on results of BLAST
      homology analysis. Molecular masses of Nod1 and Nod2 were 6145.06 and 6360.07 Da,
      respectively, as determined by mass spectrometric analysis. The two peptides
      displayed pH-dependent antibacterial activity against various bacteria that was
      more potent at pH 5.4 than pH 7.4, but they did not inhibit fungal growth at
      either pH levels. Their antibacterial activity was due to membranolytic action,
      which was assayed by SYTOX-green uptake. In addition, both peptides were
      virtually noncytolytic for human erythrocytes and mammalian cells. 

PMID- 22632467
TI  - On the psychotropic effects of carbon dioxide.
AB  - It has been well established that the inhalation of Carbon Dioxide (CO2) can
      induce in humans an emotion closely replicating spontaneous panic attacks, as
      defined by current psychiatry nosology. The purpose of this review is to provide
      a critical summary of the data regarding CO2's psychopharmacological properties
      and underlying mechanisms. The authors review the literature on the human and
      animal response for the exposure of exogenous CO2 focusing on five points of
      interest: 1) the early history of the use of CO2 as an anesthetic and therapeutic
      agent, 2) the subjective effects of breathing CO2 at different concentrations in
      humans, 3) the use of CO2 in experimental psychiatric research as an experimental
      model of panic, 4) the pharmacological modulation of CO2-induced responses, and
      5) the putative neurobiological mechanisms underlying the affective state induced
      by CO2. The authors conclude with an evolutionary-inspired notion that CO2 might
      act as an agent of a primal emotion serving a homeostatic function, in the
      control of respiration and acid-base balance.

PMID- 22632468
TI  - Genetics of anxiety disorders - status quo and quo vadis.
AB  - Clinical genetic studies propose a strong genetic contribution to the
      pathogenesis of anxiety disorders with a heritability of about 30-67%. The
      present review will give an overview of linkage studies, association studies and
      genome-wide association studies (GWAS) yielding support for some candidate genes.
      Additionally, first evidence for gene-environment interactions between candidate
      genes of anxiety disorders and stressful life events will be reported. On a
      systems level, neural activation correlates of anxiety-relevant emotional
      processing and neurophysiological measures such as peripheral sympathetic
      activity or the startle reflex have been shown to be potentially driven by
      vulnerability genes of anxiety disorders. Promising current approaches to further
      dissect the genetic underpinnings of anxiety disorders such as next generation
      sequencing, epigenetic analyses and pharmaco-/ psychotherapy-genetics will be
      presented. Genetic research in anxiety disorders will be discussed with respect
      to its potential benefit for future efforts to develop innovative and
      individually tailored therapeutic approaches for patients with anxiety disorders.

PMID- 22632469
TI  - Pharmacological innovations for posttraumatic stress disorder and medication-
      enhanced psychotherapy.
AB  - Posttraumatic stress disorder (PTSD) is a common condition for which existing
      treatments are ineffective for many patients. Recent discoveries in the
      neurobiology of learning and memory, along with expanding knowledge of how those
      systems are impacted by the biology of the stress response, have opened new
      arenas for potential medication treatments for PTSD. We conducted a review of
      registered clinical trials investigating the efficacy of new agents for PTSD. The
      glucocoritcoid and adrenergic signaling systems are the most frequent targets of
      these investigational approaches to the prevention and treatment of PTSD.
      Additional trials are evaluating modulation of other CNS targets, including
      neurosteroids, glutamate, gamma-amino butyric acid, endocannabinoids, oxytocin,
      neurokinin/Substance P, and dopamine. A particularly exciting area of research is
      studies examining Medication-Enhanced Psychotherapy (MEP). Medications provided
      before or after exposure therapy for PTSD can enhance outcomes by: 1)
      strengthening learning and memory of fear extinction; 2) disrupting
      reconsolidation, thereby weakening fear memories; or 3) facilitating engagement
      in psychotherapy by reducing fear and enhancing openness to experience. The next
      few years promise to produce insight into the neurobiology and clinical efficacy
      of several novel approaches in the pharmacologic treatment and prevention of
      PTSD.

PMID- 22632470
TI  - Disorder-specific emotional imagery for differential and quantitative assessment
      of agoraphobia.
AB  - Visual emotional stimulation is supposed to elicit psycho-vegetative reactions,
      which are similar to as the ones elicited by exposure to actual experience.
      Visual stimulation paradigms have been widely used in studies on agoraphobia with
      and without panic disorder. However, the applied imagery has hardly ever been
      disorder- and subject- specific. 51 patients with an ICD-10 and DSM-IV diagnosis
      of agoraphobia with or without panic disorder (PDA) and matching healthy controls
      have been examined. Subjects were confronted with 146 picture showing
      characteristic agoraphobic situations (high places, narrow places, crowds, public
      transport facilities, or wide places) or pictures associated with acute physical
      emergency (panic) situations, which had been pre-selected by anxiety experts.
      Participants were asked to rate emotional arousal induced by the respective
      images on the Self- Assessment Manikin scale (SAM). Data on PDA severity (PAS)
      depressive symptoms (MADRS) and sociodemographic data were recorded. Saliva
      cortisol levels were measured before and after exposure in a second test applying
      the individually mostly feared stimuli combined with emotionally neutral pictures
      for every single patient. 117 of the PDA-specific images were rated significantly
      more fear-eliciting by patients than by healthy individuals. Sub-categorization
      into agoraphobia clusters showed differential effects of clusters with regard to
      gender distribution, severity of PDA and cortisol secretion during exposure. In
      this study disorder specific and individual characteristics of agoraphobia were
      assessed for use in future trials applying emotional imagery. It could be used
      for the differential assessment of PDA and associated neurobiological and
      psychological phenomena and in neuroimaging paradigms.

PMID- 22632471
TI  - The role of life events and HPA axis in anxiety disorders: a review.
AB  - Stressful life events and dysfunctional Hypothalamic Pituitary Adrenal (HPA) axis
      have been implicated in the pathogenesis of psychiatric disorders, including
      anxiety disorders. This paper attempts to review the existing literature on
      childhood traumata, recent life events, HPA axis functioning and their
      relationship in Post-Traumatic Stress Disorder, Panic Disorder, Generalized
      Anxiety Disorder, Obsessive Compulsive Disorder and Social Phobia. Preclinical
      and clinical models will be analyzed. Stressful life events seem to have a role
      in the onset and in the course of these disorders and HPA axis abnormalities have
      been reported in almost all anxiety disorders. The hypothesis that early
      stressful life events may provoke alterations of the stress response and thus of
      the HPA axis, that can endure during adulthood, predisposing individuals to
      develop psychopathology, will be evaluated.

PMID- 22632472
TI  - D-cycloserine as an augmentation strategy for cognitive behavioral therapy for
      anxiety disorders: an update.
AB  - Cognitive behavioral therapy (CBT) has been shown to be an effective intervention
      for anxiety disorders. However, despite its proven efficacy, some patients fail
      to respond to an adequate course of treatment. In attempts to improve the
      efficacy of CBT, researchers have augmented the core learning processes of the
      intervention with d-cycloserine (DCS), an N-Methyl-D-Aspartate partial agonist.
      This article reviews the current literature on DCS as an augmentation strategy
      for CBT for anxiety disorders. We will describe the memory enhancing properties
      of DCS, review findings from randomized controlled studies of DCS in anxious
      populations and discuss mechanism, dosing and timing issues.

PMID- 22632473
TI  - Stress response regulation in panic disorder.
AB  - Panic disorder is a frequent and disabling mental disorder characterized by
      recurrent periods or abrupt surges of intense fear or discomfort, the panic
      attacks. The clinical phenomenology of panic attacks suggests a prominent role of
      a disturbed stress response regulation in the aetiopathology of this disorder. We
      summarize the results of challenge tests of the hypothalamus-pituitary
      adrenocortical (HPA) axis in panic disorder and give an overview of studies using
      psychosocial challenge paradigms. The results of HPA axis challenge tests suggest
      an increased expression of the hypothalamic neuropeptides, but an intact negative
      feedback inhibition at the level of the pituitary. Psychosocial challenge tests
      give evidence for dissociation between the subjective stress response and the HPA
      axis response in panic disorder, which might be the result of an over-focussed
      self-monitoring leading to an enhanced stress perception despite normal HPA axis
      activation. We integrated these findings in a cognitive stress control model
      suggesting that panic disorder patients develop efficient strategies to control
      the somatic stress response despite a hypothalamic hyperdrive of the HPA axis. To
      employ these strategies at the right time, patients acquired an enhanced
      perception of stress symptoms, leading to the reported dissociation of the
      subjective and HPA axis response. It can be inferred from these findings that
      cognitive behavioral therapy addressing over-focussed self-monitoring and
      maladaptive control strategies in combination with pharmacological treatment
      against over-expression of the hypothalamic neuropeptides should be an effective
      treatment in severe forms of panic disorder, which corresponds with recent
      treatment guidelines.

PMID- 22632474
TI  - Neuropeptides as therapeutic targets in anxiety disorders.
AB  - In addition to the classical neurotransmitters, neuropeptides represent an
      important class of modulators for affective behaviors and associated disorders,
      such as anxiety disorders. Many neuropeptides are abundantly expressed in brain
      regions involved in emotional processing and anxiety behaviors. Moreover, risk
      factors for anxiety disorders such as stress modulate the expression of various
      neuropeptides in the brain. Due to the high prevalence of anxiety disorders and
      yet limited treatment options, there is a clear need for more effective
      therapeutics. In this regard, the various neuropeptides represent exciting
      candidates for new therapeutic designs. In this review, I will provide an up-to
      date summary on the evidences for the involvement of seven neuropeptides in
      anxiety: corticotropin-releasing factor, urocortins, vasopressin, oxytocin,
      substance P, neuropeptide Y and galanin. This review will cover the behavioral
      effects of these neuropeptides in animal models of anxiety by both genetic and
      pharmacological manipulations. Human studies indicating a role for these
      neuropeptides in anxiety disorders will also be discussed.

PMID- 22632475
TI  - Neuroimaging of serotonin system in anxiety disorders.
AB  - A large body of research including animal and human studies has confirmed the
      crucial role of the serotonin (5-HT) system in the regulation of anxiety-related
      behaviour and traits. In the past decade, the functional status of the 5-HT
      system in anxiety disorders has been regularly investigated by novel neuroimaging
      techniques, such as single-photon emission computed tomography (SPECT) and
      positron emission tomography (PET). Although these studies shed more light on
      several aspects of the 5-HT functioning in patients with anxiety disorders, the
      current knowledge about the specific role of the 5-HT system in particular
      anxiety phenotypes remains fragmentary. In this paper, we review the available
      data from SPECT and PET imaging studies of the 5-HT system in anxiety disorders,
      attempt to dissect the involvement of the 5-HT in neural circuits of anxiety and
      discuss some issues that need to be considered for further research in this area.

PMID- 22632476
TI  - Panicogens in patients with Post-Traumatic Stress Disorder (PTSD).
AB  - Symptom provocation has proved its worth for understanding the pathophysiology of
      diseases and in general for the development of new therapeutic approaches in the
      medical field. In the research of anxiety disorders, investigations using
      experimentally induced panic attacks by various agents, such as sodium lactate,
      carbon dioxide, cholezystokinine-tetrapetid etc., have a long tradition and allow
      the exploration of usually naturally occuring spontaneous psychopathological
      phenomena under controlled conditions. Post-Traumatic Stress Disorder (PTSD) is a
      prevalent disorder that can develop following exposure to an extreme traumatic
      event. In DSM-IV it is currently classified as an anxiety disorder and shares
      phenomenological similarities with panic disorder. The use of panicogenic
      challenge tests is also an interesting neurobiological approach to learn more
      about the nature of PTSD and may be a possibility to develop new therapeutic
      strategies for the treatment of PTSD symptoms. Not only panic anxiety, but also
      flashbacks and other dissociative symptoms can be provoked by several panicogens
      in PTSD. The purpose of this review is to evaluate studies using panicogens in
      PTSD. Methodological short-comings of current studies and needed directions of
      further research are discussed.

PMID- 22632477
TI  - Distinct panicogenic activity of sodium lactate and cholecystokinin tetrapeptide
      in patients with panic disorder.
AB  - BACKGROUND: The validity of experimentally induced panic attacks as a model to
      study the pathophysiology of panic disorder has been questioned. Unspecific,
      unpleasant and aversive effects as well as specific patterns of psychovegetative
      symptoms pointing to different subtypes of panic disorder patients have been
      observed. These findings raise the question of challenge paradigms as a valuable
      tool to identify different vulnerabilities in patients with panic disorder.
      METHODS: We compared the two most widely studied panicogenic drugs sodium lactate
      and cholecystokinine tetrapeptide (CCK-4) with placebo in 25 patients with panic
      disorder and matched healthy control subjects. Psychophysiological changes were
      measured using the Acute Panic Inventory (API) and visual analogue scales for
      anxiety and arousal. RESULTS: In patients with panic disorder 18 out of 25
      experienced a sodium lactate- or a CCK-4 induced panic attack. Lactate or CCK-4
      induced symptoms and induced panic attacks were only correlated in healthy
      controls, but not in patients with panic disorder. CONCLUSION: The mechanisms of
      lactate and CCK-4 induced panic attacks are distinct in panic disorder patients
      but not in healthy controls. Different neurobiological vulnerabilities may be
      uncovered by different challenges.

PMID- 22632478
TI  - Differences in saccadic eye movements in subjects at high and low risk for panic
      disorder.
AB  - BACKGROUND: Panic disorder (PD) has a strong genetic component showing high
      heritability rates and familial aggregation. Moreover, there is evidence for
      associations between parental PD and patterns of psychopathology. So far, little
      is known about possible endophenotypes representing premorbid vulnerability
      markers in high-risk subjects for PD. In the present study, we investigated
      saccadic eye movement (SEM) as an index of CNS inhibitory function in subjects at
      high risk for PD. METHODS: 132 healthy children at high and low familial risk for
      PD were included in the study. Basal SEM parameters were obtained using an
      electro-oculography (EOG) based system measuring peak saccadic eye velocity
      (pSEV), latency and accuracy. Moreover, with regard to self rating scales, state
      trait-anxiety (STAI-C), childhood behavioral inhibition (CSRI), and anxiety
      sensitivity (CASI) were assessed. RESULTS: There was a significant overall
      difference for basal SEM parameters across groups as revealed by MANCOVA
      (F7,118=2.184, p=.040). A significant influence was found for the covariate age,
      while gender and puberty status had no influence on SEM. High-risk (HR) subjects
      showed significantly lower pSEV. Moreover, levels of state and trait anxiety were
      higher in HR children (F1=5.429, p=.021). DISCUSSION: In our sample, measurement
      of pSEV allowed discrimination between children at high and low risk for PD.
      Since these results argue for possible alterations of saccadic function in high
      risk subjects, differences in underlying neurobiological mechanisms might be
      discussed as a possible endophenotype of PD.

PMID- 22632479
TI  - Tuning nanoparticle uptake: live-cell imaging reveals two distinct endocytosis
      mechanisms mediated by natural and artificial EGFR targeting ligand.
AB  - Therapeutic nanoparticles can be directed to cancer cells by incorporating
      selective targeting ligands. Here, we investigate the epidermal growth factor
      receptor (EGFR)-mediated endocytosis of gene carriers (polyplexes) either
      targeted with natural EGF or GE11, a short synthetic EGFR-binding peptide. Highly
      sensitive live-cell fluorescence microcopy with single particle resolution
      unraveled the existence of two different uptake mechanisms; EGF triggers
      accelerated nanoparticle endocytosis due to its dual active role in receptor
      binding and signaling activation. For GE11, an alternative EGFR signaling
      independent, actin-driven pathway is presented.

PMID- 22632480
TI  - Synthesis and physico-chemical properties in aqueous medium of all possible
      isomeric bromo analogues of benzo-1H-triazole, potential inhibitors of protein
      kinases.
AB  - In ongoing studies on the role of the individual bromine atoms of 4,5,6,7
      tetrabromobenzotriazole (TBBt) in its relatively selective inhibition of protein
      kinase CK2alpha, we have prepared all the possible two mono-, four di-, and two
      tri-bromobenzotriazoles and determined their physicochemical properties in
      aqueous medium. They exhibited a general trend of a decrease in solubility with
      an increase in the number of bromines on the benzene ring, significantly
      modulated by the pattern of substitution. For a given number of attached
      bromines, this was directly related to the electronic effects resulting from
      different sites of substitution, leading to marked variations of pK(a) values for
      dissociation of the triazole proton. Experimental data (pK(a), solubility) and ab
      initio calculations demonstrated that hydration of halogenated benzotriazoles is
      driven by a subtle balance of hydrophobic and polar interactions. The combination
      of QM-derived free energies for solvation and proton dissociations was found to
      be a reasonably good predictor of inhibitory activity of halogenated
      benzotriazoles vs CK2alpha. Since the pattern of halogenation of the benzene ring
      of benzotriazole has also been shown to be one of the determinants of inhibitory
      potency vs some viruses and viral enzymes, the present comprehensive description
      of their physicochemical properties should prove helpful in efforts to elucidate
      reaction mechanisms, including possible halogen bonding, and the search for more
      selective and potent inhibitors.

PMID- 22632481
TI  - Oral paliperidone extended-release: chemistry, pharmacodynamics, pharmacokinetics
      and metabolism, clinical efficacy, safety and tolerability.
AB  - INTRODUCTION: Paliperidone is a second-generation (atypical) antipsychotic
      approved for the treatment of schizophrenia in adults and in adolescents aged 12 
      17 years. It is also approved for the treatment of adults with schizoaffective
      disorder, both as a monotherapy and as adjunctive therapy to mood stabilizers
      and/or antidepressants. Paliperidone is the active metabolite of risperidone.
      AREAS COVERED: The purpose of this review is to describe the pharmacokinetic
      profile of paliperidone and its clinical implications in the treatment of
      schizophrenia and schizoaffective disorder. Background information is also
      provided regarding chemistry, pharmacodynamics, clinical efficacy and
      safety/tolerability data. EXPERT OPINION: The recommended dose of paliperidone
      extended-release (ER) in adults is 6 mg/day and no initial dose titration is
      required. Higher doses may provide additional benefit as well as dose-related
      increases in some adverse reactions. The maximum recommended dose is 12 mg/day.
      Peak plasma concentrations are reached approximately 24 h after dosing.
      Pharmacokinetics are dose-proportional. Terminal half-life is approximately 23 h.
      Renal excretion is the major route of elimination. Although paliperidone is the
      active metabolite of risperidone, paliperidone's route of metabolism and
      elimination is quite different from that for risperidone and paliperidone ER may
      be preferred over risperidone when liver disease, drug-drug interactions or other
      alterations in metabolism render the appropriate dosing of risperidone difficult
      to determine for an individual patient. The use of paliperidone ER will need to
      be considered within the context of its cost and availability as risperidone is
      now a generic product.

PMID- 22632482
TI  - An introduction to mixed models and joint modeling: analysis of valve function
      over time.
AB  - An important target of many clinical studies is to identify biomarkers, including
      risk scores, with strong prognostic capabilities. While biomarker evaluations are
      commonly utilized to predict the progress of the disease at single time points,
      appropriate statistical tools to assess the prognostic value of serial biomarker
      evaluation are rarely used. The goal of this paper is to demonstrate flexible and
      appropriate statistical methodology to assess the predictive capability of serial
      echocardiographic measurements of allograft aortic valve function. Moreover, the
      concept of joint modeling of longitudinal and survival data to optimally utilize
      the relationship between repeated valve function measurements and time-to-death
      or time-to-reoperation, is introduced and illustrated. Optimal and suboptimal
      methods are illustrated using a prospective cohort of patients who survived
      aortic valve or root replacement with an allograft valve and who were followed
      clinically and echocardiographically over time.

PMID- 22632483
TI  - Prisoners on death row should be accepted as organ donors.

PMID- 22632484
TI  - Invited commentary.

PMID- 22632485
TI  - Invited commentary.

PMID- 22632486
TI  - Induction chemoradiation is not superior to induction chemotherapy alone in stage
      IIIA lung cancer.
AB  - BACKGROUND: The optimal treatment strategy for patients with operable stage IIIA
      (N2) non-small cell lung cancer is uncertain. We performed a systematic review
      and meta-analysis to test the hypothesis that the addition of radiotherapy to
      induction chemotherapy prior to surgical resection does not improve survival
      compared with induction chemotherapy alone. METHODS: A comprehensive search of
      PubMed for relevant studies comparing patients with stage IIIA (N2) non-small
      cell lung cancer undergoing resection after treatment with induction chemotherapy
      alone or induction chemoradiotherapy was conducted using PRISMA (Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses) standards. Hazard
      ratios were extracted from these studies to give pooled estimates of the effect
      of induction therapy on overall survival. RESULTS: There were 7 studies that met
      criteria for analysis, including 1 randomized control trial, 1 phase II study, 3
      retrospective reviews, and 2 published abstracts of randomized controlled trials.
      None of the studies demonstrated a survival benefit to adding induction radiation
      to induction chemotherapy versus induction chemotherapy alone. The meta-analysis
      performed on randomized studies (n=156 patients) demonstrated no benefit in
      survival from adding radiation (hazard ratio 0.93, 95% confidence interval 0.54
      to 1.62, p=0.81), nor did the meta-analysis performed on retrospective studies
      (n=183 patients, hazard ratio 0.77, 95% confidence interval 0.50 to 1.19,
      p=0.24). CONCLUSIONS: Published evidence is sparse but does not support the use
      of radiation therapy in induction regimens for stage IIIA (N2). Given the
      potential disadvantages of adding radiation preoperatively, clinicians should
      consider using this treatment strategy only in the context of a clinical trial to
      allow better assessment of its effectiveness.

PMID- 22632487
TI  - Invited commentary.

PMID- 22632488
TI  - Invited commentary.

PMID- 22632489
TI  - Midterm benefits of preoperative statin therapy in patients undergoing isolated
      valve surgery.
AB  - BACKGROUND: Recent data have suggested that statins are associated with reduced
      early mortality and cardiovascular events after valvular heart surgery. The
      midterm effects of preoperative statin therapy in the setting of valvular heart
      surgery are presently unclear. METHODS: All patients (n=2,120) who underwent a
      valvular procedure between April 2004 and April 2010 were identified. Patients
      undergoing concomitant coronary artery bypass graft surgery were excluded. Two
      patient groups were studied: those who received preoperative statin therapy
      (n=663; 31.3%) and those who did not (n=1,457; 68.7%). Propensity score matching
      resulted in 381 matched pairs, thus addressing baseline risk imbalances. Thirty
      day mortality, readmission rates, postoperative complications, and length of stay
      were analyzed. Late survival was ascertained by the Social Security Death Index.
      RESULTS: In the matched group, 30-day mortality was 1.3% (5 of 381) for statin
      treated patients versus 4.2% (16 of 381) for statin-untreated patients (p=0.03).
      After a mean follow-up of 33+/-23 months, statin therapy was associated with
      significantly reduced mortality (hazard ratio 0.63, 95% confidence interval: 0.43
      to 0.93, p=0.019), independent of known cardiac risk factors. Weighted log rank
      tests revealed that the mortality difference between the two cohorts occurred
      early after surgery (p=0.015). Statin users were less likely to be readmitted to
      the intensive care unit (3.4% versus 8.1%, p=0.01). There were no other
      significant differences between the two groups in terms of postoperative
      complications and length of stay. CONCLUSIONS: Preoperative statin administration
      is associated with early reductions in mortality among patients undergoing
      isolated valvular heart surgery, leading to improved late survival. Future
      prospective analyses are warranted to optimize statin therapy in this patient
      population.

PMID- 22632490
TI  - Invited commentary.

PMID- 22632491
TI  - Invited commentary.

PMID- 22632492
TI  - Invited commentary.

PMID- 22632493
TI  - Invited commentary.

PMID- 22632494
TI  - Invited commentary.

PMID- 22632495
TI  - Invited commentary.

PMID- 22632496
TI  - Invited commentary.

PMID- 22632497
TI  - Prospective clinical study of a novel left atrial appendage occlusion device.
AB  - PURPOSE: This Food and Drug Administration-approved investigational device exempt
      trial assessed the safety and efficacy of a novel device for external left atrial
      appendage (LAA) exclusion. DESCRIPTION: Delivery tool and implant consisting of
      connectors imbedded in a compliant, soft silicone applied to the base of the LAA
      flush with the external wall was assessed. EVALUATION: Patients in this
      prospective, multicenter trial were undergoing elective, nonendoscopic cardiac
      operations. A core laboratory independently assessed all intraprocedural and 90
      day transesophageal echocardiograms. Sixty patients (37 men), aged 33 to 86
      years, enrolled. The mean LAA application time was 27 seconds. Transesophageal
      echocardiograms at 90 days were available in 54 patients, and no leaks were
      detected. The residual LAA cavity exceeded 6 mm in 5 patients. One delivery
      device failed to close, and an adjunctive suture was required to complete LAA
      exclusion. One patient required adjunct sutures at a small tear site related to
      manual manipulation after fastener application. CONCLUSIONS: The study
      demonstrated safety and efficacy of this LAA exclusion device, offering an
      alternative to manual suturing or staples with or without reinforcement.

PMID- 22632498
TI  - Recovery of lung perfusion after sleeve resection for tuberculous bronchial
      stenosis.
AB  - Parenchyma-sparing main bronchial sleeve resection is a safe and effective
      procedure to restore impaired lung function. We present a case illustrating
      recovery of lung perfusion in a 24-year-old woman with dyspnea on exertion
      because of bronchial tuberculosis. Bronchoscopic examination revealed pin-hole
      stenosis of the left main bronchial orifice. 99mTc-macroaggregated albumin
      perfusion scanning revealed essentially absent left lung perfusion. Because of
      bronchomalacia in the distal portion, six rings of the left main bronchus were
      resected by carinoplasty. Symptoms abated and perfusion recovered to a large
      extent 2 months later. She became pregnant and delivered successfully 12 months
      postoperatively.

PMID- 22632500
TI  - Pulmonary metastatic giant cell tumors presenting as totally hyalinized and
      ossified nodules.
AB  - We report a case of giant cell tumor of the left distal femur with simultaneous
      bilateral pulmonary metastases. Pathologic examination of the left lung nodule
      showed a metastatic giant cell tumor with a noncontinuous ossified rim, and the
      right lung nodules were totally hyalinized or ossified without residual giant
      cell tumor components. Hyalinization was a consistent finding in both the primary
      bone lesion and the pulmonary metastases. Because the patient did not receive
      chemotherapy or radiotherapy before her surgical procedure, we believe that these
      changes represent spontaneous tumor regression.

PMID- 22632499
TI  - Conservative management of a bilothorax resulting from blunt hepatic trauma.
AB  - Pleurobiliary fistula after blunt abdominal trauma is rare. We report a case
      managed with tube thoracostomy alone, without the need for biliary system
      drainage.

PMID- 22632501
TI  - Pancreatic adenocarcinoma arising from esophageal duplication.
AB  - Esophageal duplication is a rare congenital malformation containing different
      types of tissues. We report the case of a woman with a large mediastinal tumor.
      After surgical resection, histologic examination showed pancreatic adenocarcinoma
      arising from esophageal duplication. Adjuvant chemotherapy was given briefly
      afterward.

PMID- 22632502
TI  - Huge lymphangiomatosis of the esophagus.
AB  - Lymphangioma of the esophagus is an extremely rare submucosal benign tumor. Most
      esophageal lymphangiomas reported in the literature are smaller than 2 cm in
      diameter and can be removed using endoscopy. We report a case of lymphangioma of
      the esophagus with 2 huge lesions (10*2.5*1 cm and 6*5*4 cm) that were completely
      resected by open thoracotomy and enucleation. The patient recovered without any
      complications.

PMID- 22632503
TI  - Second chance for a totally thoracoscopic video-assisted pulmonary vein isolation
      for atrial fibrillation.
AB  - Thoracoscopic surgery for atrial fibrillation (AF) is an attractive and emerging
      treatment modality. However, when a bleeding occurs access for hemostasis is
      limited. Therefore, a sternotomy might be necessary to stop the bleeding and
      continue the operation. We report 2 patients with a periprocedural bleeding in
      whom sternotomy could be prevented by tamponading the bleeding, interrupting the
      operation and resuming 3 weeks later. Our cases show that sternotomies can be
      prevented and that there is a second chance for thoracoscopic surgery for AF.

PMID- 22632504
TI  - Chronic histological transmurality of high-intensity focused ultrasound ablation.
AB  - We evaluated histologic results for surgical left maze with an high-intensity
      focused ultrasound (HIFU) energy source. Two patients came to our attention 6 and
      48 months, respectively, after ablation concomitant to a valve procedure. Tissue
      specimens, obtained from the lesion site on the mitral isthmus and from the "box
      lesion" around the pulmonary veins were analyzed histologically. A complete
      transmural lesion was found in all specimens. Chronic lesions exhibited
      replacement of the muscular band with connective tissue. The atrial wall
      maintained normal thickness and vascularization. HIFU ablation represents an
      acceptable energy source to create transmural lesions on the beating human left
      atrium.

PMID- 22632505
TI  - Intra-atrial rerouting and maze procedure for an adult patient in cor
      triatriatum, persistent left superior vena cava, and atrial fibrillation.
AB  - A combination of cor triatriatum and persistent left superior vena cava without
      communication to the coronary sinus is uncommon. A 62-year-old male with this
      diagnosis in conjunction with atrial fibrillation underwent successful
      intracardiac repair done with a unique method. After a maze procedure and
      enlargement of the route from the pulmonary veins to the mitral valve, a GoreTex
      graft was used to reroute the left superior vena cava into the right atrium and
      to close two thirds of the circumference of the patient's atrial septal defect;
      the rest of the defect was closed with another GoreTex patch.

PMID- 22632506
TI  - Mitral stenosis caused by an amplatzer occluder device used to treat a
      paravalvular leak.
AB  - Paravalvular leaks following valve replacement can result in heart failure and
      hemolysis. Surgical intervention is the treatment of choice, but it carries
      substantial risk of morbidity and mortality. Percutaneous techniques using
      devices designed for congenital heart disease are increasingly applied to the
      treatment of paravalvular leaks. We present the case of a mitral paravalvular
      leak treated with an Amplatzer occluder device. Unfortunately, the device
      occluded flow through the mitral valve, resulting in symptomatic mitral stenosis
      requiring surgical intervention.

PMID- 22632507
TI  - Composite vein graft reconstruction for infected descending aortic prosthesis.
AB  - We report a case of successful in situ replacement with a superficial
      femoropopliteal vein panel graft for Dacron graft infection of the thoracic
      aorta. A 75-year-old man presented with septicemia and pseudoaneurysm caused by
      methicillin resistant staphylococcus aureus 2 years after Dacron graft
      replacement of the mid-descending aortic aneurysm. The patient underwent in situ
      replacement with a panel graft constructed of 3 deep vein panels after excision
      of the infected Dacron graft. The patient is free of infection and doing well
      over 2 years after surgery.

PMID- 22632508
TI  - Transapical endovascular deployment of a stent-graft in the thoracic descending
      aorta.
AB  - We report the case of a 74-year-old man with a large aneurysm (60 mm) of the
      descending thoracic aorta. Because of severe calcification and kinking of the
      iliac vessels, the expected access-related complication during the endovascular
      repair urged us to search for an alternative strategy. Having good experience
      with transcatheter aortic valve implantation, we thought that the transapical
      approach may be the best option in this case. The stent-graft was successfully
      deployed through the heart apex without any complications. The postoperative
      imaging showed an excellent result.

PMID- 22632509
TI  - Histopathology of the longest-lived saphenous vein graft in a patient with
      Kawasaki disease.
AB  - The patency rate of saphenous vein grafts (SVGs) for children with Kawasaki
      disease (KD) tends to decline during the early years after coronary artery bypass
      grafting (CABG). Although degenerative changes have been considered the main
      cause of SVG occlusion, there have been no reports on the histopathologic
      features of the SVG in patients with KD. We herein describe a redo off-pump total
      arterial revascularization in a 43-year-old man with KD, 34 years after the first
      CABG using SVG. The histopathologic examination of the longest-lived SVG
      demonstrated that graft occlusion was mainly caused by the diffuse intimal
      hyperplasia.

PMID- 22632510
TI  - Temporary fenestration using venoatrial extracorporeal membrane oxygenation after
      the Fontan operation.
AB  - A 28.7-month-old male child who had undergone a Norwood operation and
      bidirectional cavopulmonary shunt at the age of 5 days and 6.6 months,
      respectively, underwent the extracardiac conduit Fontan operation. After the
      operation, high-volume resuscitation was needed, which led to high central venous
      pressure (CVP) and low arterial oxygen saturation. Venoatrial extracorporeal
      membrane oxygenation (ECMO) was initiated between the superior vena cava and the
      right atrium with one third of the expected normal cardiac output. This low-flow
      venoatrial ECMO immediately terminated the vicious cycle caused by high venous
      pressure in the Fontan circulation. He was weaned from ECMO and discharged home.

PMID- 22632511
TI  - A bizarre aortic dissection.

PMID- 22632512
TI  - Resection of multiple recurrent cardiac myxomas in an adult man with Carney's
      complex.

PMID- 22632513
TI  - Isolated unroofed coronary sinus on three-dimensional computed tomographic
      imaging.

PMID- 22632514
TI  - A video-assisted endotracheal suture technique for correction of distal tracheal
      laceration after intubation.
AB  - The incidence of tracheal laceration is 1 of 20,000 intubations. The most
      frequently affected area is the posterior tracheal wall (membranous). Risk
      factors include several forced attempts at intubation, inexperience of the
      clinician, tracheal introducers (guidewires) that protrude beyond the tip of the
      tube, and emergency procedures. Surgical treatment of tracheal lacerations can be
      by a transtracheal suture technique or a right thoracotomy. Using the concept of
      minimally invasive surgical procedures, we reported the treatment of 2 patients
      with tracheal lacerations greater than 5 cm in the distal trachea that were
      treated with endotracheal video-assisted suturing using a cervical incision.

PMID- 22632515
TI  - Surgisis mesh for tracheal reconstruction.
AB  - Esophagectomy is a commonly performed procedure that has a high morbidity rate.
      Postesophagectomy anastomotic leaks are not uncommon; however fistulas to the
      airways remain a rare and often catastrophic complication. Although most fistulas
      occur from a direct communication between a failed anastomosis and an adjacent
      airway, other risk factors have been identified, such as tracheal ischemia from
      extensive mediastinal dissection, intraoperative tracheal injuries, and cuff
      necrosis from prolonged intubation. Despite advancements in the management of
      sepsis, leaks and fistulas are still associated with a high mortality rate and
      continue to challenge esophageal surgeons.

PMID- 22632516
TI  - Simplified rat lung transplantation using a new cuff technique.
AB  - We introduce a new procedure for orthotopic left lung transplantation in rats.
      First, cuffs are attached to vessels or bronchi in both donors and recipients.
      Next, the cuffs are anastomosed by interposing pieces of the donor's descending
      aorta. Anastomosis time is markedly reduced to approximately 10 minutes.
      Transplantations were completed in 8 rats without technical errors. This rat lung
      transplantation technique is a straightforward method any surgeon can perform.

PMID- 22632517
TI  - Repair of left atrioventricular valve cleft defects with patch augmentation.
AB  - Operations for left atrioventricular valve insufficiency after repair of an
      atrioventricular septal defect can be challenging. Repair techniques largely
      depend on closure of the residual cleft in the anterior leaflet in conjunction
      with a posterior annuloplasty. Profound deficiencies in anterior leaflet tissue
      can make primary cleft closure impractical. A simplified technique, in which
      cleft closure is supported by triangular-shaped patch material, is presented
      along with results in 13 patients.

PMID- 22632518
TI  - Robert R. Shaw, MD: thoracic surgical hero, Afghanistan medical pioneer, champion
      for the patient, never a surgical society president.
AB  - Dr Robert R. Shaw arrived in Dallas to practice Thoracic Surgery in 1937, as John
      Alexander's 7th Thoracic Surgical Resident from Michigan University Medical
      Center. Dr Shaw's modus operandi was, "You can accomplish almost anything, if you
      don't care who gets the credit." He was a remarkable individual who cared the
      most about the patient and very little about getting credit for himself. From
      1937 to 1970, Dr Shaw established one of the largest lung cancer surgical centers
      in the world in Dallas, Texas. It was larger than M.D. Anderson and Memorial
      Sloan-Kettering Hospitals put together regarding the surgical treatment of lung
      cancer patients. To accomplish this, he had the help of Dr Donald L. Paulson, who
      trained at the Mayo Clinic and served as Chief of Thoracic Surgery at Brook Army
      Hospital during the Second World War. Following the War, because of his love for
      Texas, he ended up as a partner of Dr Shaw in Dallas. Together, they pursued the
      development of this very large surgical lung cancer center. Dr Shaw and his wife
      Ruth went to Afghanistan with Medico multiple times to teach men modern cardiac
      and thoracic surgery. They also served as consultants on Medico's Ship of Hope in
      Africa. Dr Shaw initiated multiple new operations including: 1) resection of
      Pancoast's cancer of the lung after preoperative irradiation; 2) upper lobe of
      the lung bronchoplasty, reattaching (and saving) the lower lobe to prevent the
      "disabling" pneumonectomy; and 3) resections of pulmonary mucoid impaction of the
      lung in asthmatics. Because of his humility and giving "the credit to others," Dr
      Shaw was never President of a major medical or surgical association.

PMID- 22632519
TI  - Is a bronchopleural fistula a contraindication to pleurodesis?

PMID- 22632520
TI  - The need for alternative methods of cardiopulmonary resuscitation when sternal
      compression is contraindicated.

PMID- 22632522
TI  - Additional applications of rapid pacing.

PMID- 22632523
TI  - Use of "maximal regurgitant area" as the sole parameter for evaluation of
      severity of recurrent mitral regurgitation after mitral valve repair: importance
      of the American Society of Echocardiography Guidelines.

PMID- 22632526
TI  - Potential risk of hyponatremia using histidine-tryptophan-ketoglutarate solution
      during pediatric cardiopulmonary bypass.

PMID- 22632527
TI  - Does ketorolac improve graft patency after coronary artery bypass grafting?

PMID- 22632530
TI  - Successful treatment of thyrotoxic crisis after esophagectomy in an elderly woman
      with hyperthyroidism.
AB  - We describe herein a case of thyrotoxic crisis after esophagectomy in a 64-year
      old woman with esophageal carcinoma and well-controlled hyperthyroidism. On the
      fourth postoperative day, she had palpitations, abdominal pain, fever, and
      tachycardia, which were similar to the symptoms of an anastomotic leak. There was
      no evidence to indicate the existence of an anastomotic leak after examination.
      We were confused at first. After turning to Burch and Wartofsky's scoring system,
      we finally diagnosed thyrotoxic crisis and then prescribed several agents for
      emergency treatment, including propylthiouracil, metoprolol tartrate, and
      hydrocortisone. Afterward, she recovered and was discharged safely.

PMID- 22632531
TI  - Ruptured diaphragmatic eventration: a rare cause of acute postpartum dyspnea.
AB  - Rupture of a maternal diaphragmatic hernia (DH) during pregnancy is a rare but
      significant complication. We describe a case of a maternal ruptured DH,
      presenting as acute postpartum dyspnea, which required urgent operative repair.
      We report our surgical strategy and review the key concepts in the
      multidisciplinary management of this condition.

PMID- 22632532
TI  - Mesenchymal cystic hamartoma of the lung.
AB  - Mesenchymal cystic hamartoma (MHC) of the lung is a very rare disease with an
      indolent clinical course and might be easily misdiagnosed as pleuropulmonary
      blastoma and other uncommon cystic lung lesions. We present a case of a 43-year
      old woman who had sudden dyspnea resulting from a spontaneous right-sided
      pneumothorax. Computed tomography revealed multiple bilateral nodules and cysts
      of the right lung. Pathologically, the cysts and nodules were composed of
      primitive mesenchymal cells. The walls of the cysts were lined with normal
      respiratory epithelium and the nodules were permeated by scattered airways that
      were also lined with normal respiratory epithelium. Based on the combination of
      pathologic and clinical features, we made the diagnosis of MHC. One and one-half
      years after thoracotomy the patient is well without evidence of recurrence.

PMID- 22632533
TI  - Benign metastasizing leiomyoma: a rare cause of multiple pulmonary nodules.
AB  - Benign metastasizing leiomyoma (BML) is a rare cause of pulmonary nodules that
      occurs when uterine leiomyomas metastasize to the lung. The management of these
      lesions varies from resection and hysterectomy to nonsurgical treatments such as
      hormonal therapy. We report a case of a 45-year-old woman with multiple nodules
      of the right lung identified during preoperative imaging before her hysterectomy
      for uterine fibroids.

PMID- 22632534
TI  - Pulmonary ossifications seen centrally in a lung tumor.
AB  - Pulmonary ossifications are classified as either dendriform or nodular, according
      to their histologic appearance. Both seem to be distributed similarly and are
      often confined to the lower lobes of the lung. These ossifications may be
      included in the differential diagnosis of a solitary pulmonary nodule.

PMID- 22632535
TI  - Postcardiac transplant transcatheter core valve implantation for aortic
      insufficiency secondary to Impella device placement.
AB  - Conventional cardiac surgical procedures or transcatheter interventions after
      orthotopic heart transplantation are generally uncommon. We report the case of a
      45-year-old woman who developed severe aortic insufficiency after insertion of a
      5-L Impella device 16 weeks after heart transplantation. After joint evaluation
      by the transcatheter valve team, transcatheter aortic valve implantation was
      planned because of associated comorbid conditions. A 29-mm CoreValve prosthesis
      (Medtronic, Minneapolis, MN) was inserted percutaneously. At 6 months after
      prosthesis implantation, the patient was asymptomatic in New York Heart
      Association functional class II, and the echocardiogram showed a mean
      transvalvular gradient of 1 mm Hg, an aortic valve area of 1.5 cm2, and no
      paravalvular aortic insufficiency.

PMID- 22632536
TI  - Anterior translocation of the right pulmonary artery for relief of airway
      compression in the repair of distal aortopulmonary window and interrupted aortic
      arch.
AB  - Airway compression by dilated right pulmonary artery (RPA) in infants with
      congenital heart disease can cause severe respiratory insufficiency and increase
      postoperative morbidity. Anterior aortopexy can be a good solution. However, in a
      case in which aortic arch repair is required, anterior aortopexy might not be
      effective or can be dangerous. Anterior translocation of the RPA can be a good
      option to avoid postoperative airway obstruction. We adopted this technique in a
      one-stage complete repair of distal aortopulmonary window, aortic origin of the
      RPA, interrupted aortic arch, and ventricular septal defect in a neonate with
      compression of both main bronchi. After 37 months of follow-up, no problem was
      encountered with her airway or RPA. We describe the technique used and the
      results obtained.

PMID- 22632537
TI  - A huge transdiaphragmatic abscess detected postcholecystectomy.

PMID- 22632538
TI  - An unusual case of severe mitral regurgitation due to a focal large peri-ring
      defect in a patient with mitral valve repair.

PMID- 22632539
TI  - External fixation of proximal tracheal airway stents: a modified technique.
AB  - Treatment of subglottic and proximal tracheal stenosis for nonsurgical candidates
      includes tracheostomy, Montgomery T tubes, and silicone stents. When used in
      lesions with concomitant malacia, silicone stents have a high incidence of
      migration. We describe a simple and effective technique of securing endoluminal
      stents using an Endo Close suturing device (Coviden, Boston, MA) and an external
      silicone button in 9 consecutive patients.

PMID- 22632540
TI  - Emergency department patients with diabetes have better glycemic control when
      they have identifiable primary care providers.
AB  - OBJECTIVES: The objective was to determine if emergency department (ED) patients
      with diabetes mellitus (DM) who have primary care providers (PCPs) have better
      control of their DM than patients with no PCPs. METHODS: This was a prospective,
      cross-sectional, observation study at a large, adult, urban, academic ED with
      85,000 annual visits. ED patients with a history of DM were eligible. Patients
      with severe systemic disease, diabetic ketoacidosis (DKA), sepsis, active steroid
      use, pregnancy, or cognitive impairment were excluded. Consenting patients had
      hemoglobin A1c (HgbA1c) analysis and completed a questionnaire regarding
      demographics, lifestyle, medication usage, educational level attained, and health
      care access, including whether or not they had PCPs. HgbA1c levels were compared
      between subjects with and without PCPs using medians with interquartile ranges
      (IQRs). A continuous plot was developed to demonstrate the proportion of patients
      without PCPs (PCP-) compared to those with PCPs (PCP+) at every level of %HgbA1c
      across the entire measured range. Multivariate logistic regression analysis was
      used to determine which clinical and demographic factors obtained from the
      questionnaire were associated with improved glycemic control (increased relative
      risk [RR] of having a %HgbA1c < 8%). RESULTS: A total of 284 patients were
      screened; 227 were enrolled, had HgbA1c analysis performed, and had complete PCP,
      race, and sex information. Complete demographic data (insurance status,
      employment status, etc.) were available on 209 subjects. Sixty-four of the 227
      patients (28.2%) denied having PCPs. Median HgbA1c was 7.7% (IQR = 6.5% to 9.68%)
      in PCP+ versus 8.9% (IQR = 6.8% to 11.3%) in PCP- patients (p = 0.01). Ninety-one
      of 163 (55.8%) PCP+ subjects had a median HgbA1c < 8% versus 25 of 64 (39.1%) in
      the PCP- group (p = 0.02). After adjusting for multiple clinical and demographic
      variables, having a PCP remained significantly associated with a median HgbA1c
      value less than 8% (RR = 1.43; p = 0.04). CONCLUSIONS: Diabetes control was
      significantly better in patients with PCPs, even after adjusting for a number of
      potentially confounding social and demographic factors.

PMID- 22632541
TI  - Analysis of cytokines in the peritoneal fluid of endometriosis patients as a
      function of the menstrual cycle stage using the Bio-Plex(r) platform.
AB  - OBJECTIVE: Endometriosis is a painful disease affecting 10-15% of reproductive
      age women. Concentrations of several cytokines and angiogenic factors in
      peritoneal fluid (PF) have been found to correlate with the severity of the
      disease. However, levels of some analytes vary across the menstrual cycle, and an
      ideal biomarker of endometriosis has not yet been identified. We have compared
      the PF concentrations of different cytokines in proliferative and secretory
      phases in women with and without the disease using the Bio-Plex platform.
      METHODS: PF was aspirated during laparoscopy (N = 133) and the PF concentrations
      of 18 cytokines from Bio-Plex panels I and II determined with the serum protocol.
      RESULTS: Increased PF concentrations of IL-6, IL-18, eotaxin, and MCP-1 were
      found in endometriosis with no changes with menstrual cycle. Levels of IL
      12(p70), ICAM-1, and GRO-alpha were higher in the secretory phase, while eotaxin
      concentrations were lower. CONCLUSION: Of the 18 cytokines tested, IL-6, IL-18
      and MCP-1 were the best PF markers of endometriosis.

PMID- 22632542
TI  - Differential effects of colchicine in blood mononuclear cells of patients with
      Behcet disease in relation to colchicine responsiveness.
AB  - BACKGROUND: Colchicine, a first-line drug for the treatment of Behcet disease
      (BD), inhibits caspase-1 activation and inflammatory cytokine production.
      However, therapeutic and preventive effects are not observed in some patients
      with BD. OBJECTIVE: To explore whether the effects of colchicine on
      proinflammatory cytokine expression and cell death in peripheral blood
      mononuclear cells (PBMCs) from patients with BD are associated with
      responsiveness to colchicine. METHODS: Activation of caspase-1, transcription and
      secretion of interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha and IL-6,
      and release of lactate dehydrogenase (LDH) in PBMCs isolated from healthy
      controls and patients with BD were analysed in the presence or absence of
      colchicine and upon stimulation with lipopolysaccharide (LPS) plus a caspase-1
      activator. RESULTS: Colchicine significantly modulated monosodium urate-induced
      IL-1beta release, LPS-stimulated LDH release, and basal transcript levels of TNF
      alpha and IL-6 in healthy controls and BD colchicine responders, but not in BD
      colchicine nonresponders. Notably, colchicine showed contrasting effects on LPS
      stimulated IL-1beta transcription, i.e. it increased in responders but decreased
      in nonresponders. Also, higher levels of TNF-alpha and IL-6 transcripts were
      observed in LPS-stimulated PBMCs from nonresponders compared with responders.
      CONCLUSIONS: This study shows different effects of colchicine on PBMCs from
      patients with BD according to their responsiveness to colchicine. Predicting
      responsiveness to colchicine in patients with BD may, therefore, be possible by
      examining alterations in IL-1beta transcript levels in LPS-stimulated PBMCs after
      colchicine treatment.

PMID- 22632544
TI  - Exposure of single-walled carbon nanotubes impairs the functions of primarily
      cultured murine peritoneal macrophages.
AB  - It is increasingly important to understand the single-walled carbon nanotubes'
      (SWCNTs) immune response as their increasingly biomedical researches and
      applications. Macrophages and T cells play important roles in scavenging foreign
      materials and pathogens and regulating immune response. In this work, primarily
      cultured murine peritoneal macrophages and purified splenic T cells were utilised
      to determine the toxic effects of SWCNTs and acid-functionalised SWCNTs (AF
      SWCNTs) on the immune system, especially on macrophage functions. Macrophages
      were exposed to 0-50 MUg/ml of CNTs for 24 h and no significant cytotoxicity was
      found by live/dead and annexin-V-FITC/PI analyses. The TEM images revealed that
      AF-SWCNTs were engulfed mostly through phagocytosis and located in lysosomes of
      macrophages. Measurement of mitochondrial membrane potential and proteasome
      subunit gene expression demonstrated that 10 and 50 MUg/ml AF-SWCNTs could damage
      mitochondrial function and proteasome formation in a concentration-dependent
      manner. Functional analyses revealed that the percentage of phagocytic cells were
      affected significantly by 20 MUg/ml CNTs, and 5 MUg/ml AF-SWCNTs inhibited the
      phagocytic efficiency of latex beads in macrophages. The accessory cell function
      was affected by both AF-SWCNTs and SWCNTs at concentrations of 10 and 50 MUg/ml,
      respectively. Furthermore, AF-SWCNT biased naive T-cell differentiation to Th1
      type by inducing the production of IFN-gamma and TNF, implying the potential risk
      of Th1-associated diseases (e.g. autoimmune diseases and inflammation) on AF
      SWCNT exposure.

PMID- 22632545
TI  - Sources of weaning advice, comparisons between formal and informal advice, and
      associations with weaning timing in a survey of UK first-time mothers.
AB  - OBJECTIVE: The aim of the present study was to explore knowledge of the UK
      weaning guidelines and the sources of weaning advice used by UK first-time
      mothers. DESIGN: An online survey of UK parents; analysed using mixed methods.
      SETTING: Participants were recruited from a selection of parenting websites that
      hosted a link to the survey. SUBJECTS: In total, 1348 UK first-time mothers were
      included in the analysis. RESULTS: Knowledge of the guidelines was high (86 %)
      and associated with later weaning (P < 0.001), although 43 % of this sample
      weaned before 24 weeks. The majority of parents used multiple sources of
      information, the most influential being the health visitor (26 %), the Internet
      (25 %) and books (18 %). Fifty-six per cent said they received conflicting
      advice. Younger mothers and those of lower educational attainment were more
      likely to be influenced by advice from family, which was likely to be to wean
      earlier. Furthermore, those most influenced by their mother/grandmother were less
      likely to have accurate knowledge of the guidelines. In this population the
      Internet was used for weaning advice across all sociodemographic groups and was
      associated with a later weaning age, independently of sociodemographic factors (P
      < 0.001). Data from responses to a free-text question are used in illustration.
      CONCLUSIONS: The study suggests that first-time mothers have a good understanding
      of the weaning guidelines but seek weaning information from multiple sources,
      much of which is conflicting. Informal sources of weaning advice appear most
      influential in younger mothers and those of lower educational attainment, and
      result in earlier weaning.

PMID- 22632567
TI  - Effect of intraperitoneal PERIDANTM concentrate adhesion reduction device on
      clinical findings, infection, and tissue healing in an adult horse
      jejunojejunostomy model.
AB  - OBJECTIVE: To evaluate the effect of PERIDANTM Concentrate on clinical findings,
      infection, and tissue healing in adult horses undergoing celiotomy and
      jejunojejunostomy. STUDY DESIGN: Block randomized blinded experimental in vivo
      study. ANIMALS: Adult horses (n = 12). METHODS: Horses had jejunojejunostomy at 2
      sites and were administered 5 L of diluted PERIDANTM Concentrate (6 horses) or
      Lactated Ringer's Injection (LRS) control intraperitoneally (6 horses) before
      body wall closure. Postoperative monitoring comprised physical examinations,
      serial hematology, coagulation and chemistry panels, and ultrasonographic
      examination. Horses were euthanatized 10 days postoperatively. Anastomoses and
      linea alba incisions were tested for mechanical strength; and tissue healing,
      inflammation, and infection were assessed by histological evaluation. Data were
      analyzed using a mixed model ANOVA. Level of significance was P < .05. RESULTS:
      No physical examination differences were observed between groups. Statistically
      significant differences were observed in leukocyte and neutrophil counts,
      prothrombin time, antithrombin III activity, intestinal bursting pressures, and
      histologic healing grade in the mid region of the linea alba. These differences
      were minimal, and of no observable clinical significance. Other blood variable
      and histologic differences between groups were not significant. CONCLUSIONS:
      PERIDANTM Concentrate was safely administered intraperitoneally to healthy horses
      undergoing celiotomy and anastomosis.

PMID- 22632568
TI  - Identification, localization and function of glutamate-gated chloride channel
      receptors in the honeybee brain.
AB  - Glutamate-gated chloride channels (GluCls) are members of the cys-loop ligand
      gated ion channel superfamily whose presence has been reported in a variety of
      invertebrate tissues. In the honeybee, a single gene, amel_glucl, encoding a
      GluClalpha subunit, was found in the genome but both the pattern of expression of
      this gene in the bee brain and its functional role remained unknown. Here we
      localised the expression sites of the honeybee GluClalpha subunit at the mRNA and
      protein levels. To characterise the functional role of GluCls in the honeybee
      brain, we studied their implication in olfactory learning and memory by means of
      RNA interference (RNAi) against the GluClalpha subunit. We found that the
      GluClalpha subunit is expressed in the muscles, the antennae and the brain of
      honeybees. Expression of the GluClalpha protein was necessary for the retrieval
      of olfactory memories; more specifically, injection of dsRNA or siRNA resulted in
      a decrease in retention performances ~24 h after injection. Knockdown of
      GluClalpha subunits impaired neither olfaction nor sucrose sensitivity, and did
      not affect the capacity to associate odor and sucrose. Our data provide the first
      evidence for the involvement of glutamate-gated chloride channels in olfactory
      memory in an invertebrate.

PMID- 22632569
TI  - Climate change adaptation: where does global health fit in the agenda?
AB  - Human-induced climate change will affect the lives of most populations in the
      next decade and beyond. It will have greatest, and generally earliest, impact on
      the poorest and most disadvantaged populations on the planet. Changes in climatic
      conditions and increases in weather variability affect human wellbeing, safety,
      health and survival in many ways. Some impacts are direct-acting and immediate,
      such as impaired food yields and storm surges. Other health effects are less
      immediate and typically occur via more complex causal pathways that involve a
      range of underlying social conditions and sectors such as water and sanitation,
      agriculture and urban planning. Climate change adaptation is receiving much
      attention given the inevitability of climate change and its effects, particularly
      in developing contexts, where the effects of climate change will be experienced
      most strongly and the response mechanisms are weakest. Financial support towards
      adaptation activities from various actors including the World Bank, the European
      Union and the United Nations is increasing substantially. With this new global
      impetus and funding for adaptation action come challenges such as the importance
      of developing adaptation activities on a sound understanding of baseline
      community needs and vulnerabilities, and how these may alter with changes in
      climate. The global health community is paying heed to the strengthening focus on
      adaptation, albeit in a slow and unstructured manner. The aim of this paper is to
      provide an overview of adaptation and its relevance to global health, and
      highlight the opportunities to improve health and reduce health inequities via
      the new and additional funding that is available for climate change adaptation
      activities.

PMID- 22632570
TI  - Hip arthroscopy in patients with early arthritis.

PMID- 22632571
TI  - Challenge accepted: description of an ongoing NIH-funded randomized clinical
      trial to compare anatomic single-bundle versus anatomic double-bundle ACL
      reconstruction.

PMID- 22632573
TI  - Dynamic function of coracoclavicular ligament at different shoulder abduction
      angles: a study using a 3-dimensional finite element model.
AB  - PURPOSE: The aim of this study was to determine the acromioclavicular (AC) motion
      and change in length and tension of the coracoclavicular ligament during
      different positions of shoulder abduction using a 3-dimensional finite element
      model based on computed tomography images from normal human shoulders. METHODS:
      The right shoulders of 10 living subjects were scanned with a high-resolution
      computed tomography scanner at 0 degrees , 60 degrees , 120 degrees , and 180
      degrees  of shoulder abduction. Several modeling programs were used to simulate
      AC motion. Finite element models of the conoid and trapezoid ligaments were
      constructed based on each footprint. The tension and length changes of each
      ligament during shoulder abduction were assessed. RESULTS: The distal clavicle
      exhibited internal rotation with respect to the medial acromion at 0 degrees , 60
      degrees , 120 degrees , and full abduction (3.2 degrees  +/- 2.9 degrees , 23.2
      degrees  +/- 10.8 degrees , 20.6 degrees  +/- 3.7 degrees , and 37.1 degrees  +/-
      3.4 degrees , respectively). With horizontal motion, the clavicle translated
      posteriorly at 60 degrees  of abduction (4.4 +/- 3.4 mm) and then translated
      anteriorly at 120 degrees  and full abduction (0.4 +/- 1.6 mm and 1.9 +/- 0.4 mm,
      respectively). The lengths of the conoid ligament gradually increased at 60
      degrees  to 180 degrees  of shoulder abduction whereas those of the trapezoid
      ligament remained relatively consistent at 60 degrees  to 120 degrees  of
      abduction compared with 0 degrees  of abduction. CONCLUSIONS: The distal clavicle
      had a wide range of motion during shoulder abduction, which did not support the
      concept of synchronous motion with the scapula. The conoid and trapezoid
      ligaments functioned reciprocally during shoulder abduction. With increasing
      shoulder abduction, the length of the conoid ligament gradually increased;
      meanwhile, the trapezoid ligament was relatively consistent and then lax at full
      abduction. In particular, the conoid ligament may act as a key restraint to
      prevent excessive retraction of the scapula during shoulder abduction. CLINICAL
      RELEVANCE: The data in this study have the potential to suggest that conoid and
      trapezoid ligaments should be reconstructed separately, and rigid AC fixation in
      patients with AC separation is not recommended based on the findings of this
      study.

PMID- 22632574
TI  - Early versus late parenteral nutrition in ICU patients: cost analysis of the
      EPaNIC trial.
AB  - INTRODUCTION: The EPaNIC randomized controlled multicentre trial showed that
      postponing initiation of parenteral nutrition (PN) in ICU-patients to beyond the
      first week (Late-PN) enhanced recovery, as compared with Early-PN. This was
      mediated by fewer infections, accelerated recovery from organ failure and reduced
      duration of hospitalization. Now, the trial's preplanned cost analysis (N = 4640)
      from the Belgian healthcare payers' perspective is reported. METHODS: Cost data
      were retrieved from individual patient invoices. Undiscounted total healthcare
      costs were calculated for the index hospital stay. A cost tree based on
      acquisition of new infections and on prolonged length-of-stay was constructed.
      Contribution of 8 cost categories to total hospitalization costs was analyzed.
      The origin of drug costs was clarified in detail through the Anatomical
      Therapeutic Chemical (ATC) classification system. The potential impact of Early
      PN on total hospitalization costs in other healthcare systems was explored in a
      sensitivity analysis. RESULTS: ICU-patients developing new infection (24.4%) were
      responsible for 42.7% of total costs, while ICU-patients staying beyond one week
      (24.3%) accounted for 43.3% of total costs. Pharmacy-related costs represented
      30% of total hospitalization costs and were increased by Early-PN (+608.00
      EUR/patient, p = 0.01). Notably, costs for ATC-J (anti-infective agents) (+227.00
      EUR/patient, p = 0.02) and ATC-B (comprising PN) (+220.00 EUR/patient, p = 0.006)
      drugs were increased by Early-PN. Sensitivity analysis revealed a mean total cost
      increase of 1,210.00 EUR/patient (p = 0.02) by Early-PN, when incorporating the
      full PN costs. CONCLUSIONS: The increased costs by Early-PN were mainly pharmacy
      related and explained by higher expenditures for PN and anti-infective agents.
      The use of Early-PN in critically ill patients can thus not be recommended for
      both clinical (no benefit) and cost-related reasons. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00512122.

PMID- 22632575
TI  - Emergency slaughter of casualty cattle increases the prevalence of anthelmintic
      drug residues in muscle.
AB  - The ProSafeBeef project studied the prevalence of residues of anthelmintic drugs
      used to control parasitic worms and fluke in beef cattle in Ireland. Injured
      (casualty) cattle may enter the human food chain under certain conditions,
      verified by an attending veterinarian and the livestock keeper. An analytical
      survey was conducted to determine if muscle from casualty cattle contained a
      higher prevalence of anthelmintic drug residues than healthy (full slaughter
      weight) cattle as a result of possible non-observance of complete drug withdrawal
      periods. A validated analytical method based on matrix solid-phase dispersive
      extraction (QuEChERS) and ultra-performance liquid chromatography-tandem mass
      spectrometry was used to quantify 37 anthelmintic drugs and metabolites in muscle
      (assay decision limits, CCalpha, 0.15-10.2 ug kg-1). Of 199 control samples of
      beef purchased in Irish shops, 7% contained detectable anthelmintic drug residues
      but all were compliant with European Union Maximum Residue Limits (MRL). Of 305
      muscle samples from injured cattle submitted to abattoirs in Northern Ireland,
      17% contained detectable residues and 2% were non-compliant (containing either
      residues at concentrations above the MRL or residues of a compound unlicensed for
      use in cattle). Closantel and ivermectin were the most common residues, but a
      wider range of drugs was detected in muscle of casualty cattle than in retail
      beef. These data suggest that specific targeting of casualty cattle for testing
      for anthelmintic residues may be warranted in a manner similar to the targeted
      testing for antimicrobial compounds often applied in European National Residues
      Surveillance Schemes.

PMID- 22632576
TI  - Blood pressure and particulate air pollution in schoolchildren of Lahore,
      Pakistan.
AB  - BACKGROUND: Air pollution is a growing health problem for urban populations in
      emerging economies. The present study examines the (cross-sectional) relation
      between blood pressure and particulate air pollution in schoolchildren of Lahore
      (Pakistan). METHODS: We recruited a sample of 8-12 year-old children (mean age
      9.9 years; 45% girls) from two schools in Lahore situated in areas with low (n =
      79) and high (n = 100) air pollution, respectively. During the study period
      (January-April 2009) particulate pollution [PM(10) and PM(2.5) i.e. particles
      with aerodynamic diameters below 10 MUm or 2.5 MUm, respectively] was measured at
      the school sites with a laser operated device (Metone Aerocet 531). Blood
      pressure was measured, after 5 minutes of sitting rest, using an automated device
      (average of 5 consecutive measurements). Spot urine samples were also collected
      and concentrations of Na and K were measured. RESULTS: Mean daily values of PM2.5
      were 28.5 MUg/m(3) (SD: 10.3) and 183 MUg/m(3) (SD: 30.2), in the low and high
      pollution areas, respectively. Systolic and diastolic blood pressure were
      significantly higher in children living in the high pollution area (115.9/70.9 mm
      Hg) than in the low pollution area (108.3/66.4 mm Hg), independently of age,
      gender, height, weight, socio-economic status, passive smoking and the urinary
      concentrations of Na, K, and creatinine. CONCLUSIONS: In 8-12 year-old children,
      exposure to (traffic-related) air pollution was associated with higher systolic
      and diastolic blood pressure. These findings, if they persist, might have
      clinical relevance at older age.

PMID- 22632577
TI  - Understanding metabolic alterations in cancer cells: a promising new/old approach
      to eradicate cancer.
AB  - Alterations in several aspects of cell metabolism have recently been re
      discovered as one of the main features of most cancer cells. The three
      minireviews discuss how alterations in the glycolytic pathway, in lipid
      metabolism and in amino acid sensing may give a growth advantage to cells with
      high proliferative rates, experiencing inadequate nutrients availability.

PMID- 22632580
TI  - Pan-enteric diaphragm disease.

PMID- 22632581
TI  - Influence of dietary phytochemicals and microbiota on colon cancer risk.
AB  - Colon cancer is the third most commonly diagnosed type of cancer in the United
      States. Lifestyle and dietary patterns influence colon cancer risk both
      positively and negatively. Among the dietary factors, several plant-derived
      compounds have been found to afford colon cancer protection. These compounds
      potentially influence all aspects of colonic cellular regulation and develop
      complex interrelationships with the colonic microbiome. Increasing understanding
      of the role of microorganisms in determining the colonic environment has led to
      awareness of this important interrelationship among dietary factors and the
      microbial population. Plant-derived polyphenols are active mediators of cellular
      events, target key carcinogenic pathways, and modulate colonic microbial
      populations. In turn, the colonic microorganisms metabolize dietary compounds and
      mediate cellular events. In addition, the role of estrogen receptors in colon
      cancer and the importance of dietary components that mediate estrogen receptor
      beta are increasingly being discovered. Hence, dietary bioactive compounds and
      the intestinal microbiota create a complex milieu that directly affects the
      carcinogenic events of the colon. These relationships must be carefully
      characterized in future research to provide dietary recommendations that will
      reduce colon cancer risk. 

PMID- 22632582
TI  - Systematic review of diagnostic criteria for IBS demonstrates poor validity and
      utilization of Rome III.
AB  - BACKGROUND: In the absence of a clear biomarker for irritable bowel syndrome
      (IBS), clinical criteria are used. In this study, we conduct a systematic review
      to examine the validation and utilization of IBS criteria. METHODS: A systematic
      review was performed in two stages. The first was a review of literature from
      1978 validating IBS diagnostic criteria. The second stage of review was to select
      studies published in IBS between 1992 and 2011. This time period was divided into
      three segments (Rome I era from 1992 to 1999, Rome II era from 2000 to 2006, and
      Rome III era from 2007 to 2011). The number and type of study (RCT or other) and
      criteria used were evaluated for each era. KEY RESULTS: The first stage of the
      systematic review identified only 14 published studies validating diagnostic
      tests for IBS (with three studies evaluating more than one criterion). There were
      eight validations for Manning, three validations for Kruis, four validations for
      Rome I, three validations for Rome II, and no validation for Rome III. In the
      second review of utilization of Rome criteria, only 25.7% of published IBS papers
      used Rome III criteria during the Rome III era (Rome II was used most in 64.8% of
      studies). CONCLUSIONS & INFERENCES: This review identified that comparator groups
      varied widely between studies making comparison of criteria impossible. Manning
      criteria are the most valid and accurate criteria. More importantly, Rome III is
      not validated and is poorly adopted in clinical research trial enrollment.

PMID- 22632583
TI  - Influence of atmospheric pressure on postoperative decompensation of intraocular
      pressure in perfluorethane-filled eyes after vitrectomy.

PMID- 22632584
TI  - Lumbar lordosis rehabilitation for pain and lumbar segmental motion in chronic
      mechanical low back pain: a randomized trial.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of lumbar
      extension traction with stretching and infrared radiation compared with
      stretching and infrared radiation alone on the lumbar curve, pain, and
      intervertebral movements of patients with chronic mechanical low back pain
      (CMLBP). METHODS: This randomized clinical study with 3-month follow-up was
      completed at the Cairo University research laboratory. Eighty patients (age
      ranged from 40 to 50 years) with CMLBP and a hypolordotic lumbar spine were
      randomly assigned to traction or a comparison group. The comparison group (n =
      40) received stretching exercises and infrared radiation, whereas the traction
      group (n = 40) received lumbar extension traction in addition to stretching
      exercises and infrared radiation. The absolute rotatory angle, intervertebral
      movements, and visual analog scale were measured for all patients at 3 intervals.
      RESULTS: The results revealed a statistically significant difference between the
      groups at 2 follow-up time points compared with the baseline values for the
      translational and sagittal rotational movements of L3-L4, L4-L5, L5-S1, and L2-L3
      (posttreatment) and absolute rotatory angle (P < .01). There were no
      statistically significant changes in pain (P = .1 and .3) and L1-L2 (P = .072 and
      .076) or L2-L3 (at follow-up; P = .3), and there was no significant difference
      between all the previous variables adjusted to the groups' baseline outcome
      interaction (P > .01). CONCLUSION: Lumbar extension traction with stretching
      exercises and infrared radiation was superior to stretching exercises and
      infrared radiation alone for improving the sagittal lumbar curve, pain, and
      intervertebral movement in CMLBP.

PMID- 22632585
TI  - A randomized clinical trial of chiropractic treatment and self-management in
      patients with acute musculoskeletal chest pain: 1-year follow-up.
AB  - OBJECTIVE: We have previously reported short-term follow-up from a pragmatic
      randomized clinical trial comparing 2 treatments for acute musculoskeletal chest
      pain: (1) chiropractic treatment and (2) self-management. Results indicated a
      positive effect in favor of the chiropractic treatment after 4 and 12 weeks. The
      current article investigates the hypothesis that the advantage observed at 4 and
      12 weeks would be sustained after 1 year. In addition, we describe self-reported
      consequences of acute musculoskeletal chest pain at 1-year follow-up. METHODS: In
      a nonblinded, randomized controlled trial undertaken at an emergency cardiology
      department and 4 outpatient chiropractic clinics, 115 consecutive patients with
      acute chest pain of musculoskeletal origin were included. After the baseline
      evaluation, patients were randomized to 4 weeks of either chiropractic treatment
      or self-management, with posttreatment questionnaire follow-up 52 weeks later.
      The primary outcome measures were change in pain intensity (11-point box
      numerical rating scale) and self-perceived change in pain (7-point ordinal
      scale). RESULTS: Both groups experienced decreases in pain, positive global, self
      perceived treatment effect, and increases in the 36-Item Short Form Health Survey
      scores. No statistically significant differences were observed between groups at
      the 1-year follow-up, and we could not deduce a common trend in favor of either
      intervention. CONCLUSIONS: At the 1-year follow-up, we found no difference
      between groups in terms of pain intensity and self-perceived change in chest pain
      in the first randomized clinical trial assessing chiropractic treatment vs
      minimal intervention for patients with acute musculoskeletal chest pain. Further
      research into health care utilization and use of prescriptive medication is
      warranted.

PMID- 22632586
TI  - Prevalence of low back and pelvic pain during pregnancy in a Norwegian
      population.
AB  - OBJECTIVE: The purpose of this study was to investigate the cumulative prevalence
      of low back pain (LBP), pelvic pain (PP), and lumbopelvic pain during pregnancy,
      including features possibly associated with development of pregnancy-related PP,
      in an unselected population of women. METHODS: A retrospective cohort study was
      conducted in which all women giving birth at Stavanger University hospital in a 4
      month period were asked to participate and to fill in a questionnaire on
      demographic features, pain, disability, and Oswestry Disability Index. Inclusion
      criteria were singleton pregnancy of at least 36 weeks and competence in the
      Norwegian language. RESULTS: Nearly 50% of the women experienced moderate and
      severe PP during pregnancy. Approximately 50% of them had PP syndrome, whereas
      the other half experienced lumbopelvic pain. Ten percent of the women experienced
      moderate and severe LBP alone. These pain syndromes increased sick leave and
      impaired general level of function during pregnancy. Approximately 50% of women
      with PP had pain in the area of the symphysis. The analysis of risk factors did
      not present a unidirectional and clear picture. CONCLUSIONS: Pelvic pain in
      pregnant women is a health care challenge in which moderate and severe pain
      develops rather early and has important implications for society. The observed
      associations between possible causative factors and moderate and severe LBP and
      PP in this study may, together with results from other studies, bring some
      valuable insights into their multifactorial influences and provide background
      information for future studies.

PMID- 22632587
TI  - Effects of muscular stretching and segmental stabilization on functional
      disability and pain in patients with chronic low back pain: a randomized,
      controlled trial.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of 2 exercise
      programs, segmental stabilization exercises (SSEs) and stretching of trunk and
      hamstrings muscles, on functional disability, pain, and activation of the
      transversus abdominis muscle (TrA), in individuals with chronic low back pain.
      METHODS: A total of 30 participants were enrolled in this study and randomly
      assigned to 1 of 2 groups as a function of intervention. In the segmental
      stabilization group (SS), exercises focused on the TrA and lumbar multifidus
      muscles, whereas in the stretching group (ST), exercises focused on stretching
      the erector spinae, hamstrings, and triceps surae. Severity of pain (visual
      analog scale and McGill pain questionnaire) and functional disability (Oswestry
      disability questionnaire) and TrA muscle activation capacity (Pressure
      Biofeedback Unit, or PBU) were compared as a function of intervention.
      Interventions lasted 6 weeks, and sessions happened twice a week (30 minutes
      each). Analysis of variance was used for intergroup and intragroup comparisons.
      RESULTS: As compared with baseline, both treatments were effective in relieving
      pain and improving disability (P < .001). Those in the SS group had significantly
      higher gains for all variables. The stretching group did not effectively activate
      the TrA (P = .94). CONCLUSION: Both techniques improved pain and reduced
      disability. In this study, SS was superior to muscular stretching for the
      measured variables associated with chronic low back pain.

PMID- 22632588
TI  - Investigation of the effects of a centrally applied lumbar sustained natural
      apophyseal glide mobilization on lower limb sympathetic nervous system activity
      in asymptomatic subjects.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of a manual
      mobilization technique on indirect measures of sympathetic nervous system
      activity. METHODS: Forty-five healthy volunteers participated in this randomized,
      single-blinded, parallel-group 3-arm design (experimental, sham [placebo], and
      control group), comprising 15 subjects each. For the experimental group, lumbar
      mobilization involving an active movement, the Mulligan sustained natural
      apophyseal glide (SNAG), was applied on L4 spinous process by an experienced
      manual therapist. Sustained natural apophyseal glides were performed in sitting
      with active flexion (6 times * 3 sets). The sham technique simulated the SNAG
      without applying any force. In the control group, participants were placed in a
      static sitting position throughout the experiment. Measures of skin conductance
      in the lower limbs (L4 dermatome) were recorded to reflect sympathetic nervous
      system activity in the preintervention, periintervention, and postintervention
      periods. Differences in percentage change of skin conductance were analyzed with
      analysis of variance and post hoc tests. RESULTS: Lumbar SNAG produced
      sympathoexcitation compared with the control group in the intervention period (P
      = .04). No significant difference was found between SNAG and sham groups, and no
      statistically significant difference was found between groups in the final rest
      period. CONCLUSION: The results of this study showed that, in asymptomatic
      participants, both lumbar SNAG and sham techniques performed on L4/5
      intervertebral joint with active flexion induced a sympathoexcitatory response in
      lower limbs compared with the control group.

PMID- 22632589
TI  - Effect of high-velocity, low-amplitude treatment on superoxide dismutase and
      glutathione peroxidase activities in erythrocytes from men with neck pain.
AB  - OBJECTIVE: This study investigates the analgesic effect of high-velocity, low
      amplitude (HVLA) manipulation and antioxidant enzymes superoxide dismutase (SOD)
      and glutathione peroxidase (GPx) in erythrocytes of men with neck pain. METHODS:
      Twenty-two men with neck pain of mechanical origin who were aged 20 to 50 years,
      were nonsmokers, had a sedentary lifestyle, had no comorbidities, and were not in
      adjuvant therapy underwent 6 sessions of HVLA chiropractic manipulation 3 times a
      week for 2 weeks. Patients were treated by the same chiropractor and under the
      same conditions. Blood samples were collected before the beginning of the
      treatment and at the end of the third and last session. Erythrocytes were
      separated from blood and then processed to determine SOD and GPx activities. The
      quadruple visual scale and the Neck Disability Index were used to demonstrate the
      analgesic effect of treatment. The results were analyzed by repeated-measures
      analysis of variance followed by Bonferroni posttest. Differences were considered
      significant when P was less than .05. RESULTS: Despite the tendency to reduction
      in SOD and increase in GPx activities, there was no significant change after the
      treatment. CONCLUSION: High-velocity, low-amplitude treatment for 6 sessions in
      men with neck pain did not affect systemic SOD and GPx activities. Despite the
      absence of significant changes, this study is important because it is the first
      to investigate the activities of SOD and GPx in patients with neck pain treated
      with HVLA spinal manipulation.

PMID- 22632590
TI  - Immediate effects of ischemic compression on neck function in patients with
      cervicogenic cephalic syndrome.
AB  - OBJECTIVE: Cervicogenic cephalic syndrome (CCS), a group of diseases, consists of
      cervicogenic headache and dizziness. These symptoms may cause loss of physical
      function compared with other headache and dizziness disorders. The purpose of
      this case-control study was to assess the clinical effects of ischemic
      compression (IC) in patients with CCS. METHODS: Twenty-seven subjects with
      chronic neck pain (persisting for >3 months) and 26 healthy volunteers were
      examined. Subjects with organic lesion of the ear, nose, throat, eye, or central
      nervous system were excluded. The CCS group received IC over the maximal tender
      points of the origin of the posterior nuchal muscle. Sensory organization test
      (SOT) scores, cervical range of motion (ROM), and isometric strength of neck were
      measured before IC and after IC. RESULTS: The ROM of the cervical spine increased
      in all directions after IC (P < .0083) in the CCS group, and isometric strength
      in the CCS group rose in all directions after IC (P = .000). There was a
      significant difference in ankle strategy score under the sway-referenced vision
      and fixed support condition (P = .003) between the control group and CCS before
      IC. The ankle strategy score of the CCS group improved substantially after IC
      under eyes closed and sway-referenced support conditions (P = .003). The visual
      and vestibular ratios in the CCS group also increased after IC (P = .006 and P =
      .002, respectively). CONCLUSIONS: The findings of this study showed that ROM of
      the cervical spine and isometric strength increased in all directions, and the
      SOT scores showed increased postural stability under conditions with swayed
      reference support after IC in the CCS group. The ratios for vestibular and visual
      function also increased after IC in the CCS group.

PMID- 22632591
TI  - Influence of different upper cervical positions on electromyography activity of
      the masticatory muscles.
AB  - OBJECTIVE: The aim of this study was to determine the activity of the masseter
      and anterior temporalis muscles in relation to different positions of the upper
      cervical spine during maximal voluntary isometric clenching by surface
      electromyography (EMG). METHODS: This was a cross-sectional study with a repeated
      measures design performed using 25 asymptomatic subjects (13 female and 12 male;
      mean age, 31 years; SD, 8.51). The EMG activity of the masseter and anterior
      temporalis muscles was recorded bilaterally during maximal clenching at neutral
      position and during extension, flexion, ipsilateral lateral flexion,
      contralateral lateral flexion, and ipsilateral and contralateral rotations in
      maximal flexion. In addition, the upper cervical range of motion and mandibular
      excursions were assessed. The EMG activity data were analyzed using a 3-way
      analysis of variance in which the factors considered were upper cervical
      position, sex (male and female), and side (right and left), and the hypothesis of
      importance was the interaction side x position. RESULTS: The 3-way analysis of
      variance detected statistically significant differences between the several upper
      cervical positions (F = 13.724; P < .001) but found no significant differences
      for sex (F = 0.202; P = .658) or side (F = 0.86; P = .53) regarding EMG activity
      of the masseter muscle. Significant differences were likewise observed for
      interaction side x position for the masseter muscle (F = 12.726; P < .001). The
      analysis of the EMG activity of anterior temporalis muscle did not produce
      statistically significant differences (P > .05). CONCLUSION: This preliminary
      study suggests that the upper cervical movements influence the surface EMG
      activity of the masseter muscle. These findings support a model in which there
      are interaction between the craniocervical and the craniomandibular system.

PMID- 22632592
TI  - Anterioposterior spinal curvatures and magnitude of asymmetry in the trunk in
      musicians playing the violin compared with nonmusicians.
AB  - OBJECTIVE: Playing an instrument often requires a certain posture and asymmetric
      position that may affect the anteroposterior spinal curvatures and may lead to
      postural asymmetry. The aim of the study was to evaluate the spinal curvatures in
      the sagittal plane and the magnitude of asymmetries in the trunk in the frontal
      plane in a group of music students in comparison with a control group. METHODS:
      The group of 67 students aged 20 to 26 years was made up of 2 subgroups: the
      musicians (violin playing students of the Academy of Music in Wroclaw) and the
      control group (physical therapy students who played no instruments). The
      examination included an interview, measuring of somatic characteristics, and
      evaluation of body posture by means of the photogrammetric method. RESULTS: The
      spinal curvatures of the instrumentalists in the sagittal plane differ from the
      control group mainly in terms of length and depth parameters. Compared with the
      control group, the musicians were characterized by statistically more
      significantly longer and deeper thoracic kyphosis (P < .01) and more shallow
      lumbar lordosis (P < .05), a greater angle of thoracic kyphosis (P < .005), and a
      smaller inclination angle of the thoracolumbar and lumbosacral section of the
      spine (P < .01). CONCLUSION: In the group of musicians, the asymmetries in the
      area of shoulders and waist triangles as well as the distance of the spinous
      processes from the C7 to S1 line were more frequent.

PMID- 22632593
TI  - Effects of foot orthotics on running economy: methodological considerations.
AB  - OBJECTIVE: The purpose of the study was to collect preliminary data to address
      methodological considerations that may impact subject-specific reactions to foot
      orthotics during running. METHODS: Six endurance-trained recreational runners
      recruited from a chiropractic college campus wore their preferred running shoes
      and then inserted either their custom-made orthotics during 1 testing session or
      their shoe-fitted insoles during the other testing session. Comfort perception
      was measured for each footwear condition. Measurements of oxygen consumption
      (VO2) at several moderate exercise intensities, to mimic recreational running,
      generated an individual's economy-of-running line. Predicted running velocity at
      VO(2max) (vVO2max) was calculated as an index of endurance performance. Lower
      extremity muscle activity was recorded. Descriptive statistics, a repeated
      measures analysis of variance model, and a paired t test were used to document
      any systematic changes in running economy, lower extremity muscle activities, and
      vVO2max within and across subjects as a function of footwear conditions. RESULTS:
      Decreases in VO2 at several moderate exercise intensities (F((1,5)footwear) =
      10.37, P = .023) and increases in vVO2max (t(5) = 4.20, P = .008) occurred in all
      6 subjects while wearing their orthotic intervention vs their shoe-fitted
      insoles. There were no consistent changes in lower extremity muscle activity.
      CONCLUSIONS: Methodological decisions to use a sustained incremental exercise
      protocol at several moderate exercise intensities and to measure comfort
      perception of a custom-molded foot orthosis were effective at documenting
      systematic improvements in running economy among the 6 recreational runners
      tested. The development of a less physically demanding sustained exercise
      protocol is necessary to determine underlying neuromuscular mechanisms and/or
      clinical effectiveness of orthotic interventions.

PMID- 22632594
TI  - Lipid peroxides and glutathione status in human progenitor mononuclear (U937)
      cells following exposure to low doses of nickel and copper.
AB  - Effects of Cu(2+), Ni(2+) or Cu(2+) + Ni(2+) on lipid peroxide and glutathione
      (GSH) levels in U937 cells were investigated. Cells were treated with 0, 5, 10,
      and 20 uM of Cu(2+) and/or Ni(2+) and H(2)O(2) (0.01 mM) and incubated for 24
      hours at 37 degrees C. Lipid peroxides were measured by the thiobarbituric acid
      assay (TBA). GSH intracellular levels were assayed by the GSH assay kit from
      EMD/Calbiochem (San Diego, California, USA). Cu(2+) or Ni(2+) significantly (P <
      0.01) increased lipid peroxides in a dose-dependent manner, compared to controls.
      The effect was more pronounced for Cu(2+), compared to the Ni(2+)-treated
      samples. Cu(2+) + Ni(2+) increased lipid peroxides in a significant (P < 0.001),
      dose-dependent manner, compared to Cu(2+) or Ni(2+) alone (i.e., ratio of 2.5:1
      fold for combined versus single treatments, respectively). Cu(2+) or Ni(2+)
      significantly decreased GSH levels in U937 cells, with the effect being
      pronounced for Cu(2+). Cu(2+) + Ni(2+) metal ions significantly (P < 0.001)
      depleted cells of GSH in a dose-dependent manner. Ethylene diamine tetraacetic
      acid (EDTA) at 50 or 100 uM moderately reduced the Cu(2+)- or Ni(2+)-induced
      effects on GSH levels. Interestingly, GSH levels generally decreased to half
      (except for the combined metal dose of 20 uM at 100 uM EDTA) of its level at the
      highest metal concentration tested for both the single or combined treatments. In
      conclusion, multiple exposures of cells to metal ions may be lethal to cells,
      compared to their single treatments.

PMID- 22632595
TI  - Enantioselective Diels-Alder reaction of alpha-(acylthio)acroleins: a new entry
      to sulfur-containing chiral quaternary carbons.
AB  - A catalytic and enantioselective Diels-Alder reaction of alpha
      (carbamoylthio)acroleins induced by an organoammonium salt of chiral triamine is
      described. alpha-(Carbamoylthio)acroleins are designed and synthesized as new
      sulfur-containing dienophiles for the first time. The Diels-Alder reaction
      affords chiral tertiary thiol precursors with up to 91% ee.

PMID- 22632596
TI  - Validity and reliability of instruments designed to measure factors influencing
      the overuse of antibiotics.
AB  - BACKGROUND: Antibiotic overuse is a global public health issue that is influenced
      by several factors. The degree and prevalence of antibiotic overuse is difficult
      to measure directly. A more practical approach, such as the use of a psycho
      social measurement instrument, might allow for the observation and assessment of
      patterns of antibiotic use. STUDY OBJECTIVE: The aim of this paper is to review
      the nature, validity, and reliability of measurement scales designed to measure
      factors associated with antibiotic misuse/overuse. DESIGN: This study is
      descriptive and includes a systematic integration of the measurement scales used
      in the literature to measure factors associated with antibiotic misuse/overuse.
      The review included 70 international scientific publications from 1992 to 2010.
      MAIN RESULTS: Studies have presented scales to measure antibiotic misuse.
      However, the workup of these instruments is often not mentioned, or the scales
      are used with only early-phase validation, such as content or face validity.
      Other studies have discussed the reliability of these scales. However, the full
      validation process has not been discussed in any of the reviewed measurement
      scales. CONCLUSION: A reliable, fully validated measurement scale must be
      developed to assess the factors associated with the overuse of antibiotics.
      Identifying these factors will help to minimize the misuse of antibiotics.

PMID- 22632597
TI  - The threat of carbapenem-resistant Enterobacteriaceae in Lebanon: an update on
      the regional and local epidemiology.
AB  - Bacterial resistance to antimicrobial agents is increasing. Complex resistant
      mechanisms have resulted in a wide spectrum of species and strains with multidrug
      resistant patterns. In addition to the production of extended-spectrum-beta
      lactamases (ESBLs), Gram-negative rods have acquired the capacity to hydrolyze
      carbapenem antibiotics by means of carbapenemases. The enzyme that has gained the
      most publicity recently is the New Delhi metallo-beta-lactamase (NDM-1). This
      enzyme and others are now spreading from their homeland on the Indian
      subcontinent to other continents, primarily via medical tourists. This spread
      contributes to be a global threat in an era when no potent antibiotics are
      expected to be developed. Patients coming from countries where antimicrobial use
      is not restricted, such as Iraq, may harbor similar organisms. Reports from the
      Middle East and Arabian countries describing the occurrence of carbapenem
      resistant Enterobacteriaceae are rare. In this communication, an update on the
      epidemiology, prevalence and mechanisms of carbapenem-resistant
      Enterobacteriaceae in Lebanon and the surrounding region will be addressed in
      addition to the detection methods and required infection control practices.

PMID- 22632598
TI  - Risk of bloodborne pathogen exposure among Zambian healthcare workers.
AB  - PURPOSE: Understanding the risks of bloodborne pathogen transmission is
      fundamental to prioritizing interventions when resources are limited. This study
      investigated the risks to healthcare workers in Zambia. DESIGN: A survey was
      completed anonymously by a convenience sample of workers in three hospitals and
      two clinics in Zambia. Respondents provided information regarding job category,
      injuries with contaminated sharps, hepatitis B vaccination status and the
      availability of HIV post-exposure prophylaxis (PEP). RESULTS: Nurses reported the
      largest number of injuries. The average annual sharps injury rate was 1.3
      injuries per worker, and service workers (housekeepers, laundry, ward assistants)
      had the highest rate of these injuries, 1.9 per year. Injuries were often related
      to inadequate disposal methods. Syringe needles accounted for the largest
      proportion of injuries (60%), and 15% of these injuries were related to
      procedures with a higher-than-average risk for infection. Most workers (88%)
      reported the availability of PEP, and only 8% were fully vaccinated against
      hepatitis B. CONCLUSIONS: The injury risks identified among Zambian workers are
      serious and are exacerbated by the high prevalence of bloodborne pathogens in the
      population. This suggests that there is a high risk of occupationally acquired
      bloodborne pathogen infection. The findings also highlight the need for a
      hepatitis B vaccination program focused on healthcare workers. The risks
      associated with bloodborne pathogens threaten to further diminish an already
      scarce resource in Zambia - trained healthcare workers. To decrease these risks,
      we suggest the use of low-cost disposal alternatives, the implementation of cost
      sensitive protective strategies and the re-allocation of some treatment resources
      to primary prevention.

PMID- 22632599
TI  - An audit of inpatient management of community-acquired pneumonia in Oman: a
      comparison with regional clinical guidelines.
AB  - OBJECTIVE: Community-acquired pneumonia (CAP) is a major cause of morbidity and
      mortality worldwide. Herein, we present the findings from an audit of CAP
      management at a tertiary hospital in Oman. The main objective was to evaluate the
      quality of care given to patients and compare it with the standards in the Gulf
      Cooperation Council (GCC) CAP guidelines. METHODS: A retrospective case study of
      all patients admitted with CAP from June 2006 to September 2008 examined the
      adherence to standards for the diagnosis, investigation, and management of CAP,
      including the documentation of illness severity. RESULTS: The case notes of 342
      patients were reviewed. Of these, 170 patients were excluded from the study, and
      172 patients met the diagnostic criteria for inclusion. A CURB-65 severity score
      was documented for only 4 (2.3%) patients, and a smoking history was documented
      for 56 (32.6%) patients. Although 17 different antibiotic regimens were used, 115
      (67%) patients received co-amoxiclav and clarithromycin, which is the standard of
      care. Additionally, 139 (81%) patients received their first dose of antibiotics
      within four hours of hospital admission. There was no documentation of offering
      influenza or pneumococcal vaccine to high risk patients. CONCLUSION: The clinical
      coding of CAP diagnosis was poor. There was very poor adherence to the CAP
      severity assessment and the provision of preventive measures upon hospital
      discharge. The development and implementation of a local hospital-based
      integrated care pathway may lead to more successful implementation of the
      guidelines.

PMID- 22632600
TI  - Microbial quality of well water from rural and urban households in Karnataka,
      India: a cross-sectional study.
AB  - OBJECTIVE: The objective of this study was to evaluate the microbial quality of
      the well water used as a drinking source in urban and rural households. METHODS:
      A total of 80 household well water samples were analyzed by the multiple
      fermentation tube method to determine the presumptive coliform count/most
      probable number of coliforms, and the isolates were identified using standard
      procedures, followed by susceptibility testing. RESULTS: Fecal indicator
      organisms, including Escherichia coli and Enterococcus spp. were isolated from 22
      (27.5%) samples, and the majority (92.5%) of the water sources were contaminated
      with coliforms. A total of 170 bacterial isolates were obtained, including
      coliforms (70%), Enterococcus spp. (1.8%) and saprophytes (28.2%). A significant
      number of isolates were multi-drug resistant, which is a cause of concern. A
      comparison of the microbial quality of the water between urban and rural
      households revealed no significant differences. CONCLUSION: It might be prudent
      to monitor the bacteriological quality of well water at the source in addition to
      resistance profiles of the isolates.

PMID- 22632601
TI  - Detection of toxigenic Vibrio cholerae with new multiplex PCR.
AB  - OBJECTIVE: Vibrio cholerae (V. cholerae) is the etiological agent of epidemic
      cholera. In recent years, cholera has become endemic in different regions of the
      world. Traditional culture and microscopic methods are considered the standard
      for the diagnosis of V. cholerae. However, these methods require days for
      confirmation. Therefore, molecular methods that may be used for the sensitive,
      accurate, and rapid analysis of V. cholerae are urgently needed. MATERIALS AND
      METHODS: In the present investigation, a multiplex PCR assay was developed for
      the detection of virulence- and toxigenic-associated (VTA) genes (ctxA, tcpA and
      ompW). To evaluate PCR specificity, other bacteria from the Enterobacteriaceae
      family (Salmonella typhi, Shigella dysenteriae, and enterotoxigenic Escherichia
      coli) and Aeromonas hydrophila were examined. The assay sensitivity was evaluated
      using colony counting and genome dilution methods. RESULT: Our results showed
      that this PCR-based method represents an ideal tool for the rapid detection of
      VTA genes due to its simplicity, cost effectiveness, and accuracy. This multiplex
      PCR method can be used to determine the presence of VTA genes and can therefore
      distinguish V. cholerae bacteria from other Vibrio species and bacteria. This
      method can detect 10-100 CFU V. cholerae and 8.5-85 pg genomic DNA. DISCUSSION:
      This multiplex PCR method has higher sensitivity and specificity than other
      methods. The proposed test provides an appropriate and sensitive tool for
      detecting the presence of toxigenic and pathogenic V. cholerae.

PMID- 22632602
TI  - A resonance Raman enhancement mechanism for axial vibrational modes in the
      pyridine adduct of myoglobin proximal cavity mutant (H93G).
AB  - The proximal cavity mutant of myoglobin consists of a mutation of the proximal
      histidine to glycine (H93G), which permits exogenous ligands to bind to the heme
      iron. A non-native pyridine ligand can ligate to the heme to yield a five
      coordinate adduct, H93G(Pyr), that cannot be formed freely in solution since the
      six-coordinate bis-pyridine adduct is more stable than the five-coordinate
      adduct. We have used resonance Raman spectroscopy in the Soret band region of the
      heme to study the enhancement of axial vibrations of bound pyridine in the
      H93G(Pyr) adduct. The observation that the pyridine ring breathing mode (nu(1))
      and the symmetric ring stretching (nu(3)) modes are enhanced under these
      conditions is explained by a computational approach that shows that coupling of
      the pi-system of the heme with the p-orbitals of the pyridine is analogous to pi
      backbonding in diatomic ligand adducts of heme proteins. The result has the
      broader significance that it suggests that the resonance enhancement of pyridine
      modes could be an important aspect of Raman scattering of pyridine on conducting
      surfaces such as those studied in surface enhanced Raman scattering experiments.

PMID- 22632603
TI  - Organotypic systems in drug metabolism and toxicity: challenges and
      opportunities.
AB  - INTRODUCTION: The frequent failure of high-throughput screening cell-based tools
      to accurately predict in vivo responses, coupled with limitations of animal
      models in predicting human safety or drug efficacy, impairs the de-risking
      process for biotechnology/pharmaceutical companies as they make important
      decisions to enter human clinical trials. Organotypic systems strive to fill the
      gap between these screening and in vivo studies and provide a solution. AREAS
      COVERED: The authors examine the various approaches to recreate physiological
      response on the bench and trace the evolution of organotypic systems, while
      discussing intrinsic challenges and opportunities that lie ahead. Furthermore,
      they cite literature that is the foundation of several biotechnology research
      companies addressing this issue and discuss major government-funded initiatives
      to aid the development of these systems in an effort to fill this existing gap.
      EXPERT OPINION: Decisions from translational systems that bridge basic drug
      efficacy and toxicity with clinical outcome must be benchmarked against human
      relevant endpoints and clinical data for early meaningful pre-clinical decisions.
      The use of human primary cells coupled with emerging technologies that allow
      precise control of the culture environment and analysis of meaningful endpoints
      paves the way for human organotypic systems as a major initiative in de-risking
      the drug discovery and development process.

PMID- 22632604
TI  - Gaming supports youth with acquired brain injury? A pilot study.
AB  - AIM: To explore the effects of usage of the Nintendo Wii on physical, cognitive
      and social functioning in patients with acquired brain injury (ABI). METHODS:
      This multi-centre, observational proof-of-concept study included children,
      adolescents and young adults with ABI aged 6-29 years. A standardized, yet
      individually tailored 12-week intervention with the Nintendo Wii was delivered by
      trained instructors. The treatment goals were set on an individual basis and
      included targets regarding physical, mental and/or social functioning. Outcome
      assessments were done at baseline and after 12 weeks and included: the average
      number of minutes per week of recreational physical activity; the CAPE
      (Children's Assessment of Participation and Enjoyment); the ANT (Amsterdam
      Neuropsychological Tasks); the achievement of individual treatment goals (Goal
      Attainment Scaling); and quality-of-life (PedsQL; Pediatric Quality of Life
      Inventory). Statistical analyses included paired t-tests or Wilcoxon-Signed-Rank
      tests. RESULTS: Fifty patients were included (31 boys and 19 girls; mean age 17.1
      years (SD = 4.4)), of whom 45 (90%) completed the study. Significant changes of
      the amount of physical activity, speed of information processing, attention,
      response inhibition and visual-motor coordination (p < 0.05) were seen after 12
      weeks, whereas there were no differences in CAPE or PedsQL scores. Two-thirds of
      the patients reported an improvement of the main treatment goal. CONCLUSION: This
      study supports the potential benefits of gaming in children and youth with ABI.

PMID- 22632605
TI  - Guest editor's introduction.

PMID- 22632607
TI  - Target-based anti-angiogenic therapy in breast cancer.
AB  - Breast cancer is the most common female cancer. Despite advances in prevention,
      early diagnosis, and surgical treatment, its prognosis is still poor. Therefore,
      immunological and pharmacological methods of treatment have been emphasized
      recently. Prominent targets of drugs or antibodies are proteins, which are
      predominantly expressed on breast cancer cells and are simultaneously involved in
      promoting cell growth or apoptosis. However, breast cancer is a heterogeneous
      disease, because breast cancer cells may show a variety of malignant gene
      expression patterns. Therefore, it is difficult at the current state of
      technology, to apply the optimal cocktail of drugs to hit all cancer cells of any
      given patient. Under these circumstances, the option of targeting more tractable,
      normal cells surrounding the tumor instead of the less heterogeneous ones,
      preventing them from supporting tumor cell growth, became particularly
      interesting. Endothelial cells are important supporters of cancer cell growth. As
      a rule, tumors induce them to grow out and to develop a tumor vasculature, which
      enables the cancer cells to survive and to spread. The introduction of inhibitors
      of neovascularization was therefore an important milestone on the way toward
      treating breast cancer more successfully. It has already been demonstrated that
      the blockade of vascular endothelial growth results in regression of the disease
      and first clinical studies seemed to hint toward a beneficial effect on
      prolongation of survival. Nevertheless, more clinical and basic research is
      necessary to improve this therapy approach. This review will compile the
      knowledge about recently developed anti-angiogenic drugs in the treatment of
      breast cancer and will provide an overview on currently relevant clinical trials.

PMID- 22632606
TI  - Preclinical safety and pharmacokinetic profile of 3K3A-APC, a novel, modified
      activated protein C for ischemic stroke.
AB  - Activated protein C (APC), a protease with anticoagulant and cytoprotective
      activities, protects neurons and cerebrovascular endothelium from ischemic
      injury. A recombinant APC, drotrecogin alfa (activated) (DrotAA) (Xigris(r)), was
      approved by the Food and Drug Administration for the treatment of sepsis;
      however, serious bleeding was a dose-limiting side effect. A modified APC,
      containing 405 amino acid residues, 3K3A-APC, was designed to possess
      significantly reduced anticoagulant activity ( < 10 %) while maintaining full
      cytoprotective properties. The preclinical safety assessment of 3K3A-APC was
      conducted to support initiation of ischemic stroke clinical trials.The safety and
      toxicokinetics of 3K3A-APC were studied in CD-1 mice and cynomolgus monkeys.
      Multiple-dose (14-day), intravenous GLP toxicology assessed toxicity,
      histopathology, immunogenicity, and toxicokinetics.Dose-related increases in
      plasma total 3K3A-APC were observed in mice and monkeys with no evidence of
      accumulation over 14 days. The elimination T(1/2) in monkeys was 1 hour. 3K3A-APC
      was well tolerated in mice and monkeys, and no signs of 3K3A-APC toxicity were
      identified in mice or monkeys at any time. Additionally,wild-type APC (DrotAA)
      was studied to obtain comparative anticoagulant data using clotting assays.
      Anticoagulant activity of 3K3A-APC was observed in monkeys at doses of 1 and 5
      mg/kg/day .In contrast, DrotAA showed prolongation of clotting assays in monkeys
      at doses 1/10(th) of those showing effects with 3K3A-APC. Based upon the
      anticoagulant profiles, the risk for APC-induced bleeding in clinical trials of
      3K3A-APC is greatly reduced relative to wild type APC which makes this new drug a
      feasible therapy for ischemic stroke patients.

PMID- 22632608
TI  - Experimental evidence of false-positive Comet test results due to TiO2 particle-
      assay interactions.
AB  - We have studied the genotoxicity of TiO2 particles with a Comet assay on a
      unicellular organism, Tetrahymena thermophila. Exposure to bulk- or nano-TiO2 of
      free cells, cells embedded in gel or nuclei embedded in gel, all resulted in a
      positive Comet assay result but this outcome could not be confirmed by
      cytotoxicity measures such as lipid peroxidation, elevated reactive oxygen
      species or cell membrane composition. Published reports state that in the absence
      of cytotoxicity, nano- and bulk-TiO2 genotoxicity do not occur directly, and a
      possible explanation of our Comet assay results is that they are false positives
      resulting from post festum exposure interactions between particles and DNA. We
      suggest that before Comet assay is used for nanoparticle genotoxicity testing,
      evidence for the possibility of post festum exposure interactions should be
      considered. The acellular Comet test described in this report can be used for
      this purpose.

PMID- 22632610
TI  - Pathophysiology of asthma: lessons from genetic research with particular focus on
      severe asthma.
AB  - There is good evidence that both inherited and environmental factors influence
      the risk of developing asthma. Only recently, large well-designed studies have
      been undertaken with the power to identify the genetic causes for asthma, and
      methods developed in parallel with the Human Genome Project, such as gene
      expression and epigenetic studies, have made large-scale analyses of functional
      genetics possible. In this review, we discuss the recent findings from genetic
      and genomic research studies of asthma, particularly severe asthma, and highlight
      specific genes for which there are multiple lines of evidence for involvement in
      asthma pathogenesis. Bio-ontologic enrichment analyses of the most recently
      identified asthma-related genes point to attributes such as 'molecular and signal
      transducer activity' and 'immune system processes', which indicates the
      importance of immunoregulation and inflammatory response in the pathogenesis of
      asthma. Finally, we discuss how genetic and environmental factors jointly
      influence asthma susceptibility and summarize how the results may increase
      understanding of the pathophysiology of asthma-related diseases.

PMID- 22632611
TI  - Metal acquisition and virulence in Brucella.
AB  - Similar to other bacteria, Brucella strains require several biologically
      essential metals for their survival in vitro and in vivo. Acquiring sufficient
      levels of some of these metals, particularly iron, manganese and zinc, is
      especially challenging in the mammalian host, where sequestration of these
      micronutrients is a well-documented component of both the innate and acquired
      immune responses. This review describes the Brucella metal transporters that have
      been shown to play critical roles in the virulence of these bacteria in
      experimental and natural hosts.

PMID- 22632612
TI  - Identification and characterization of IgA antibodies against beta2-glycoprotein
      I in childhood Henoch-Schonlein purpura.
AB  - BACKGROUND: Henoch-Schonlein purpura (HSP) is a common IgA-mediated vasculitis in
      children. The antigenic target for IgA is to be determined. OBJECTIVE: To test
      whether beta2-glycoprotein I (beta2GPI) is an antigenic target for IgA in
      childhood HSP, and to evaluate the clinical implications and pathogenic role of
      such IgA autoantibodies. METHODS: The reactivity of patients' plasma samples and
      purified polyclonal IgA with beta2GPI, beta2GPI-derived peptides and endothelial
      cells was tested by enzyme-linked immunosorbent assay. The association between
      clinical manifestations and IgA anti-beta2GPI antibodies was also analysed.
      Finally, IgA-mediated cytotoxicity on endothelial cells was further evaluated.
      RESULTS: At the acute stage, patients with HSP had significantly higher plasma
      levels of IgA antibodies against beta2GPI than healthy controls [reference units
      (RU) 1.14 +/- 0.8 vs. 0.42 +/- 0.24, P < 0.001]. IgA anti-beta2GPI antibodies
      were associated with the presence of joint manifestations (with vs. without joint
      involvement, 1.15 +/- 0.64 vs. 0.85 +/- 0.47, P = 0.0341) and heavy proteinuria
      (with vs. without heavy proteinuria, 2.09 +/- 2.02 vs. 1.04 +/- 0.62, P =
      0.0028). Polyclonal IgA from plasma samples positive for IgA anti-beta2GPI
      antibodies bound well not only to beta2GPI with Kd values < 10(-5) mol L(-1), but
      also to some beta2GPI-dereived linear peptides (P3, P5, P7, P11 and P12).
      Moreover, beta2GPI-reactive polyclonal IgA also bound well to endothelial cells
      and induced complement-dependent cell lysis. CONCLUSION: These findings reveal
      the clinical and pathogenic relevance of IgA anti-beta2GPI antibodies in
      childhood HSP and suggest that beta2GPI may be an important autoantigen for HSP.

PMID- 22632613
TI  - In this issue/abstract thinking: treatment response in psychiatry.

PMID- 22632614
TI  - Network science and social media.

PMID- 22632615
TI  - Ethics and research with vulnerable children.

PMID- 22632616
TI  - Rage takes center stage: focus on an underappreciated aspect of pediatric
      obsessive-compulsive disorder.

PMID- 22632617
TI  - Mental health problems in young children investigated by U.S. child welfare
      agencies.
AB  - OBJECTIVE: To examine the prevalence/predictors of mental health (MH) problems
      and services use in 12- to 36-month-old children who had been investigated for
      maltreatment. METHOD: Data came from the second National Survey of Child and
      Adolescent Well-Being (NSCAW II), a longitudinal study of youth ages 0 to 17.5
      years referred to U.S. child welfare agencies. These analyses involved 1117
      children 12 to 36 months of age. Sociodemographic, social services, developmental
      and health data were collected on the children and caregivers. Outcomes were
      scores over the clinical cutoffs on the Brief Infant Toddler Social and Emotional
      Assessment (BITSEA) Scales for 12- to 18-month-olds and the Child Behavior
      Checklist (CBCL) for 19- to 36-month-olds. RESULTS: In all, 34.6% of 12 to 18
      month-olds scored high on the Problem Scale of the BITSEA, and 20.9% on the
      Competence Scale, whereas 10.0% of 19- to 36-month-olds scored over the CBCL
      clinical cut-off. Children of black ethnicity were less likely to have elevated
      scores on the BITSEA Problem Scale, whereas children who lived with a never
      married caregiver were five times more likely to have elevated scores. Competence
      problems were associated with prior child welfare history. Elevated CBCL scores
      were associated with living with a depressed caregiver. Few children with
      identified MH problems, 2.2%, received an MH service. When we added parenting
      skills training that might be related to the treatment of child problems, 19.2%
      received a service. CONCLUSIONS: Identifiable MH problems are common, but few
      children receive services for those problems. The lack of services received by
      these young, multi-challenged children is a services systems and social policy
      failure.

PMID- 22632618
TI  - Rage attacks in pediatric obsessive-compulsive disorder: phenomenology and
      clinical correlates.
AB  - OBJECTIVE: Rage attacks have been documented in youth with varied psychiatric
      disorders, but few data have been reported on the clinical characteristics and
      correlates of rage attacks among children with obsessive-compulsive disorder
      (OCD). METHOD: Participants were 86 children (ages 6-16 years) with a primary
      diagnosis of OCD. Patients and their primary caregiver were administered
      clinician-rated measures of obsessive-compulsive severity and rage severity.
      Children completed the Center for Epidemiologic Studies Depression Scale and the
      Child Sheehan Disability Scale-Child, whereas parents completed the Rage Attacks
      Questionnaire, Aberrant Behavior Checklist-Irritability Scale, Children's
      Affective Lability Scale, and Child Sheehan Disability Scale-Parent. RESULTS:
      Rage was common among youth with OCD and was associated with varied clinical
      characteristics. Rage severity accounted for functional impairment beyond the
      influence of obsessive-compulsive symptom severity; however, these relations were
      explained by the impact of family accommodation. CONCLUSIONS: These data suggest
      that rage attacks are relatively common, have a negative impact on illness
      presentation, and contribute to functional impairment above and beyond obsessive
      compulsive symptom severity. Rage may contribute to family accommodation of
      symptoms, which may further affect obsessive-compulsive symptom severity and
      impairment.

PMID- 22632619
TI  - Putting theory to the test: modeling a multidimensional, developmentally-based
      approach to preschool disruptive behavior.
AB  - OBJECTIVE: There is increasing emphasis on dimensional conceptualizations of
      psychopathology, but empirical evidence of their utility is just emerging. In
      particular, although a range of multidimensional models have been proposed, the
      relative fit of competing models has rarely been tested. Furthermore,
      developmental considerations have received scant attention. In this study, we
      tested a developmentally based, four-dimensional model of disruptive behavior
      theorized to represent the defining features of disruptive behavior at preschool
      age: Temper Loss, Noncompliance, Aggression, and Low Concern for Others. METHOD:
      Model testing was conducted in two independent samples of preschoolers:
      Clinically Enriched Sample (n = 336) and Epidemiologic Sample (n = 532). The tau
      equivalent confirmatory factor analyses were used to test the fit of the
      Developmental Model relative to three leading competing models (DSM opositional
      defiant disorder (ODD)/conduct disorder (CD) Model, "Callous" Model, and an
      "Irritable/Headstrong/Hurtful" Model). Reliability of the four dimensions was
      also tested. Validity of the dimensions was tested by predicting multi-informant,
      multi-method ratings of disruptive behavior and impairment, and incremental
      utility relative to DSM symptoms. RESULTS: In both samples, the Developmental
      Model demonstrated a superior fit compared with the competing models within the
      full sample, and across key demographic subgroups. Validity was also
      demonstrated, including incremental utility relative to DSM-IV disruptive
      behavior symptoms. CONCLUSIONS: Critical next steps for achieving scientific
      consensus about the optimal dimensional model of disruptive behavior and its
      clinical application are discussed.

PMID- 22632620
TI  - Variability among research diagnostic interview instruments in the application of
      DSM-IV-TR criteria for pediatric bipolar disorder.
AB  - OBJECTIVE: The DSM-IV-TR criteria for a manic episode and bipolar disorder (BD)
      were developed for adults but are used for children. The manner in which
      clinicians and researchers interpret these criteria may have contributed to the
      increase in BD diagnoses given to youth. Research interviews are designed to
      improve diagnostic reliability and validity, but vary in how they incorporate DSM
      IV-TR criteria for pediatric BD. METHOD: We examined DSM-IV-TR criteria and the
      descriptive text for a manic episode and the mania sections of six commonly used
      pediatric diagnostic research interviews focusing on the following:
      interpretation of DSM-IV-TR, recommendations for administration, and scoring
      methods. RESULTS: There are differences between the DSM-IV-TR manic episode
      criteria and descriptive text. Instruments vary in several ways including in
      their conceptualization of the mood criterion, whether symptoms must represent a
      change from the child's usual state, and whether B-criteria are required to co
      occur with the A-criterion. Instruments also differ on recommendations for
      administration and scoring methods. CONCLUSIONS: Given the differences between
      DSM-IV-TR manic episode criteria and explanatory text, it is not surprising that
      there is considerable variation between diagnostic instruments based on DSM-IV
      TR. These differences likely lead to dissimilarities in subjects included in BD
      research studies and inconsistent findings across studies. The field of child
      psychiatry would benefit from more uniform methods of assessing symptoms and
      determining pediatric BD diagnoses. We discuss recommendations for changes to
      future instruments, interviews, assessment, and the DSM-5.

PMID- 22632621
TI  - Developmental trajectories in adolescents and adults with autism: the case of
      daily living skills.
AB  - OBJECTIVE: This study aimed to investigate the longitudinal course of daily
      living skills in a large, community-based sample of adolescents and adults with
      autism spectrum disorders (ASD) over a 10-year period. METHOD: Adolescents and
      adults with ASD (n = 397) were drawn from an ongoing, longitudinal study of
      individuals with ASD and their families. A comparison group of 167 individuals
      with Down syndrome (DS) were drawn from a linked longitudinal study. The Waisman
      Activities of Daily Living Scale was administered four times over a 10-year
      period. RESULTS: We used latent growth curve modeling to examine change in daily
      living skills. Daily living skills improved for the individuals with ASD during
      adolescence and their early 20s, but plateaued during their late 20s. Having an
      intellectual disability was associated with lower initial levels of daily living
      skills and a slower change over time. Individuals with DS likewise gained daily
      living skills over time, but there was no significant curvature in the change.
      CONCLUSIONS: Future research should explore what environmental factors and
      interventions may be associated with continued gains in daily living skills for
      adults with ASD.

PMID- 22632622
TI  - Inattention and hyperactivity predict alterations in specific neural circuits
      among 6-year-old boys.
AB  - OBJECTIVE: Assessment of inattention and hyperactivity in preschoolers is highly
      dependent upon parental reports. Such reports are compromised by parental
      attitudes and mental health. Our study aimed to examine associations of
      inattention and hyperactivity/impulsivity from maternal reports on the Conners'
      Parent Rating Scale (CPRS) with brain morphology assessed using structural
      magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) in 6-year-old
      boys. METHOD: Large deformation diffeomorphic metric brain mapping was used to
      assess brain morphology on MRI and DTI in 96 six-year-old boys, including
      cortical thickness, subcortical shapes, and fractional anisotropy (FA) of deep
      white matter tracts (DWMTs). Linear regression examined associations between
      these measures of brain structures and mothers' CPRS ratings of their child's
      inattention and hyperactivity/impulsivity. RESULTS: Our results revealed that
      temporal and parietal cortices, as well as posterior white matter and callosal
      tracts are associated with inattention and hyperactivity/impulsivity symptoms
      among six-year-old boys. Inattention and hyperactivity/impulsivity symptoms share
      common neural circuits, but hyperactivity/impulsivity ratings associate with more
      extensive cortical areas, such as frontal regions, and with white matter tracts
      emphasizing executive control. There were no associations detected between
      inattention (or hyperactivity/impulsivity) and the shape of subcortical
      structures. CONCLUSIONS: Our results suggested specific rather than widespread
      neural circuits involved in inattention and hyperactivity/impulsivity in young
      children, which is congruent with existing findings in older children and
      adolescents, and in adults with attention-deficit/hyperactivity disorder (ADHD).
      Hence, our study supported the dimensional view of ADHD, that is, that symptoms
      of inattention and hyperactivity/impulsivity lie on a continuum.

PMID- 22632625
TI  - A functional magnetic resonance imaging study of risperidone and divalproex.

PMID- 22632623
TI  - Glutamatergic effects of divalproex in adolescents with mania: a proton magnetic
      resonance spectroscopy study.
AB  - OBJECTIVES: This study used proton magnetic resonance spectroscopy ((1)H MRS) to
      evaluate the in vivo effects of extended-release divalproex sodium on the
      glutamatergic system in adolescents with bipolar disorder, and to identify
      baseline neurochemical predictors of clinical remission. METHOD: Adolescents with
      bipolar disorder who were experiencing a manic or mixed episode (N = 25) were
      treated with open-label, extended-release divalproex (serum levels 85-125 MUg/mL)
      and underwent (1)H MRS scanning at baseline (before treatment) and on days 7 and
      28. Healthy comparison subjects (n = 15) also underwent (1)H MRS scanning at the
      same time points. Glutamate (Glu) and glutamate+glutamine (Glx) concentrations
      were measured in three voxels: anterior cingulate cortex (ACC), left
      ventrolateral prefrontal cortex (LVLPFC), and right ventrolateral prefrontal
      cortex (RVLPFC), and were compared between bipolar and healthy subjects. Within
      the bipolar subjects, Glu and Glx concentrations at baseline and each time point
      were also compared between remitters and nonremitters after divalproex treatment.
      RESULTS: At baseline, no differences in Glu or Glx concentrations between bipolar
      and healthy subjects were observed. Group (HC vs. BP) by time effects revealed an
      interaction for Glu in the ACC, and change over time effects for Glx were noted
      in the ACC in patients with bipolar disorder (increase from day 0 to day 7 and
      then a decrease from day 7 to day 28) but not in HC. Remitters had significantly
      lower baseline Glx concentrations in LVLPFC, and in remitters the change in
      LVLPFC Glu correlated with the change in YMRS score. CONCLUSIONS: Successful
      treatment of mania with divalproex may be predicted by lower baseline
      concentrations of Glx in the LVLPFC. In addition, in remitters, the degree of
      symptomatic improvement is related to the change in Glu concentrations in this
      region, suggesting that divalproex may work via modulation of the prefrontal
      glutamatergic system in youth with bipolar disorder.

PMID- 22632626
TI  - School ratings in early-onset depression.

PMID- 22632628
TI  - Bicycle helmet use and non-use - recently published research.
AB  - Bicycle traumata are very common and especially neurologic complications lead to
      disability and death in all stages of the life. This review assembles the most
      recent findings concerning research in the field of bicycle traumata combined
      with the factor of bicycle helmet use. The area of bicycle trauma research is by
      nature multidisciplinary and relevant not only for physicians but also for
      experts with educational, engineering, judicial, rehabilitative or public health
      functions. Due to this plurality of global publications and special subjects,
      short time reviews help to detect recent research directions and provide also
      information from neighbour disciplines for researchers. It can be stated that to
      date, that although a huge amount of research has been conducted in this area
      more studies are needed to evaluate and improve special conditions and needs in
      different regions, ages, nationalities and to create successful prevention
      programs of severe head and face injuries while cycling.Focus was explicit the
      bicycle helmet use, wherefore sledding, ski and snowboard studies were excluded
      and only one study concerning electric bicycles remained due to similar motion
      structures within this review. The considered studies were all published between
      January 2010 and August 2011 and were identified via the online databases Medline
      PubMed and ISI Web of Science.

PMID- 22632629
TI  - Streamlining immunoassays with immiscible filtrations assisted by surface
      tension.
AB  - Immunoassays are utilized for a wide variety of clinical and biomedical research
      applications. In typical immunoassays, analytes are captured, labeled, and
      quantified on a single surface (e.g., the bottom of a well plate). In order to
      minimize the background, this type of assay must be washed multiple times between
      each of these steps to ensure residual reagents (e.g., unbound labeling antibody)
      are removed from the system. In this manuscript, the immunoassay is fundamentally
      reconfigured, such that each reagent is confined to its own well and no wash
      steps are required. Using immiscible filtration assisted by surface tension
      (IFAST), a technique developed for nucleic acid and whole cell purifications,
      immunoassays can be drastically simplified such that all reagent manipulation is
      performed at the start of the assay (i.e., no pipetting steps are necessary
      during the assay). Analytes are bound to paramagnetic particles via antibodies
      and drawn through oil barriers between four isolated compartments: (1) sample
      well, (2) primary antibody labeling well, (3) secondary antibody labeling well,
      and (4) readout buffer well. Using this technique, we have demonstrated
      repeatable detection of as little as 188 fg of protein. IFAST immunoassay
      functionality is demonstrated by detecting a well accepted prostate cancer
      biomarker, prostate specific antigen (PSA). Assay performance was assessed by
      measuring known concentrations of recombinant PSA protein. The assay was then
      used to measure PSA concentrations in conditioned media and human plasma samples.

PMID- 22632630
TI  - A Keystone for ncRNA.
AB  - A report on the Keystone symposium 'Non-coding RNAs' held at Snowbird, Utah, USA,
      31 March to 5 April 2012.

PMID- 22632631
TI  - Risk assessment for furan contamination through the food chain in Belgian
      children.
AB  - Young, old, pregnant and immuno-compromised persons are of great concern for risk
      assessors as they represent the sub-populations most at risk. The present paper
      focuses on risk assessment linked to furan exposure in children. Only the Belgian
      population was considered because individual contamination and consumption data
      that are required for accurate risk assessment were available for Belgian
      children only. Two risk assessment approaches, the so-called deterministic and
      probabilistic, were applied and the results were compared for the estimation of
      daily intake. A significant difference between the average Estimated Daily Intake
      (EDI) was underlined between the deterministic (419 ng kg-1 body weight (bw) day
      1) and the probabilistic (583 ng kg-1 bw day-1) approaches, which results from
      the mathematical treatment of the null consumption and contamination data. The
      risk was characterised by two ways: (1) the classical approach by comparison of
      the EDI to a reference dose (RfD(chronic-oral)) and (2) the most recent approach,
      namely the Margin of Exposure (MoE) approach. Both reached similar conclusions:
      the risk level is not of a major concern, but is neither negligible. In the first
      approach, only 2.7 or 6.6% (respectively in the deterministic and in the
      probabilistic way) of the studied population presented an EDI above the
      RfD(chronic-oral). In the second approach, the percentage of children displaying
      a MoE above 10,000 and below 100 is 3-0% and 20-0.01% in the deterministic and
      probabilistic modes, respectively. In addition, children were compared to adults
      and significant differences between the contamination patterns were highlighted.
      While major contamination was linked to coffee consumption in adults (55%), no
      item predominantly contributed to the contamination in children. The most
      important were soups (19%), dairy products (17%), pasta and rice (11%), fruit and
      potatoes (9% each).

PMID- 22632632
TI  - Disability among elderly rural villagers: report of a survey from Gonoshasthaya
      Kendra, Bangladesh.
AB  - BACKGROUND: The study was set up to identify the extent and nature of difficulty
      with activities of daily living (disabilities) among elderly village residents of
      Bangladesh, to describe help currently given and to identify possible
      interventions. It was carried out at Gonoshasthaya Kendra (GK), a community
      development organization responsible for the health care of 600 villages with a
      population of some 1.5 million. METHODS: A survey card was designed and piloted
      using 12 questions on disability, elaborated from the Washington Group Disability
      questions, together with a checklist of health problems. A survey was carried out
      in 2010 in 535 villages under the care of GK since 2005, with village paramedics
      interviewing residents believed to be age 60 years or older. Respondents were
      matched where possible to data from the 2005 GK household census, giving data on
      education, occupation, socioeconomic group and smoking habit. RESULTS: Survey
      cards were completed for 43417 residents of which 17346 were matched to residents
      recorded in the GK census as born <= 1945. The proportion reporting 'much
      difficulty' on one or more functional capacities increased steadily with age,
      reaching 55% (1796/3620) among those >= 85 years. Difficulties most frequently
      reported were lifting and carrying, vision and going outside the home. At all
      ages women were more likely to report 'much difficulty' than men (OR = 1.43 (1.35
      to 1.48)), with widows and the illiterate at greater risk. Health problems,
      particularly hemiplegia, resting tremor, urinary incontinence and depression were
      strongly related to the 12 disabilities assessed. Help came almost entirely from
      family members; of 11211 villagers with 'much difficult' on at least one
      functional capacity, only 15 reported getting help outside the family.
      CONCLUSIONS: Disabled elderly residents were dependent on the family for help
      but, with family cohesiveness under threat from migration to the city, there is a
      pressing need for the development and critical evaluation of community-based
      interventions designed specifically for the elderly in poor rural societies. New
      approaches to training and practice will be needed to integrate such disability
      management into primary care.

PMID- 22632633
TI  - Safranal enhances non-rapid eye movement sleep in pentobarbital-treated mice.
AB  - AIMS: Safranal (2,6,6-trimethyl-1,3-cyclohexadiene-1-carboxaldehyde, C(10) H(14)
      O) is an active ingredient in the saffron, which is used in traditional medicine.
      It has been reported to have sedative and anti-epileptic effects, but its
      hypnotic effects remain uncertain. The aim of this study was to evaluate effects
      of safranal on sleep-wake cycle. METHODS: We established hypnotic-model mice
      treated with a low dose of pentobarbital 20 mg/kg, and administered different
      doses of safranal, vehicle, or diazepam. The change of sleep-wake cycle was
      assessed by sleep recording and c-Fos expression in the brain was analyzed by
      immunohistochemistry. RESULTS: Safranal increased the duration of non-rapid eye
      movement (NREM) sleep, shortened NREM sleep latency, and enhanced the delta power
      activity of NREM sleep. Immunohistochemical evaluation revealed that safranal
      increased c-Fos expression in the ventrolateral preoptic nucleus (VLPO), one of
      the putative sleep centers, and decreased it in the arousal histaminergic
      tuberomammillary nuclei (TMN). CONCLUSION: These findings indicate that safranal
      enhances NREM sleep in pentobarbital-treated mice. The hypnotic effects of
      safranal may be related to the activation of the sleep-promoting neurons in the
      VLPO and the simultaneous inhibition of the wakefulness-promoting neurons in the
      TMN, suggesting that safranal may be a hypnotic substance.

PMID- 22632634
TI  - Tropical diseases: definition, geographic distribution, transmission, and
      classification.
AB  - The term tropical diseases encompasses all diseases that occur principally in the
      tropics. This term covers all communicable and noncommunicable diseases, genetic
      disorders, and disease caused by nutritional deficiencies or environmental
      conditions (such as heat, humidity, and altitude) that are encountered in areas
      that lie between, and alongside, the Tropic of Cancer and Tropic of Capricorn
      belts. In tropical countries, apart from noncommunicable diseases, a severe
      burden of disease is caused by an array of different microorganisms, parasites,
      land and sea animals, and arthropods.

PMID- 22632635
TI  - Venomous bites, stings, and poisoning.
AB  - This article discusses the epidemiology, prevention, clinical features, first aid
      and medical treatment of venomous bites by snakes, lizards, and spiders; stings
      by fish, jellyfish, echinoderms, and insects; and poisoning by fish and molluscs,
      in all parts of the world. Of these envenoming and poisonings, snake bite causes
      the greatest burden of human suffering, killing 46,000 people each year in India
      alone and more than 100,000 worldwide and resulting in physical handicap in many
      survivors. Specific antidotes (antivenoms/antivenins) are available to treat
      envenoming by many of these taxa but supply and distribution is inadequate in
      many tropical developing countries.

PMID- 22632636
TI  - Transplant-associated and blood transfusion-associated tropical and parasitic
      infections.
AB  - Blood transfusion and transplantation may represent efficient mechanisms of
      spreading infectious agents to naive populations. In the developed countries, as
      a consequence of globalization, several factors such as international commerce,
      tourism, and immigration have acted as important features for the emergence or
      reemergence of infectious diseases previously referred to as tropical. This
      article reviews the relevant bacterial, protozoan and viral infections that are
      more frequently associated with blood transfusion and/or solid organ or marrow
      transplantation and may affect susceptible populations worldwide.

PMID- 22632637
TI  - Malaria: an update for physicians.
AB  - Malaria remains the most important parasitic infection in humans. There have been
      significant advances in the treatment of both nonsevere and severe malaria with
      the advent of artemisinin combination therapies and parenteral artesunate, but
      the optimum supportive management of severe malaria is unclear. A broadly
      acceptable therapy for the prevention of relapses in Plasmodium vivax infection
      has not been discovered. Globally, the priority remains to prevent infection in
      the vulnerable, to move toward elimination where feasible, and to ensure that
      effective treatment is available to all. In developed settings, prevention of
      infection and its early recognition are crucial.

PMID- 22632638
TI  - Human African trypanosomiasis.
AB  - Human African trypanosomiasis (sleeping sickness) is caused by the unicellular
      parasite Trypanosoma brucei and transmitted by tsetse flies. It occurs
      exclusively in sub-Saharan Africa, usually in rural areas affected by civil
      conflicts and neglected health systems. Reported cases are fewer than
      10,000/year, which classifies it as one of the most neglected tropical diseases.
      Because sleeping sickness is fatal if not treated, it has to be included in the
      differential diagnosis of every febrile traveler returning from a game park in
      East Africa. Elimination of the disease is considered feasible provided better
      tools for diagnosis and treatment can be made available.

PMID- 22632639
TI  - American trypanosomiasis (Chagas disease).
AB  - Chagas disease, also known as American trypanosomiasis, is a chronic infection
      caused by Trypanosoma cruzi, a protozoan parasite. It is transmitted to human
      beings mainly through the feces of infected triatomine bugs. The disease affects
      an estimated 8 to 10 million people in the Americas, putting them at risk of
      developing life-threatening cardiac and gastrointestinal complications. This
      article provides a brief update on the epidemiology, clinical manifestations,
      diagnosis, and treatment of Chagas disease.

PMID- 22632640
TI  - Cutaneous and mucocutaneous leishmaniasis.
AB  - Tegumentary leishmaniases are caused by approximately 15 species of protozoa of
      the genus Leishmania. They prevail in tropical and subtropical areas of the Old
      and New World but human mobility also makes them a medical problem in nonendemic
      areas. Clinical manifestations may comprise cutaneous and mucocutaneous forms
      that may be localized, disseminated, or diffuse in distribution and may differ in
      Old and New World leishmaniases. Diagnosis and treatment vary according to the
      clinical manifestations, geographic area, and Leishmania species involved. This
      article highlights the diversity and complexity of tegumentary leishmaniases,
      which are worsened by human immunodeficiency virus/Leishmania coinfection.

PMID- 22632641
TI  - Visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) is a vector-borne parasitic disease targeting tissue
      macrophages. It is among the most neglected infectious diseases. Classical
      manifestations of VL include chronic fever, hepatosplenomegaly, and pancytopenia.
      Most cases can be detected through serologic and molecular testing. Although
      therapy has historically relied on antimonials, newer therapeutic options include
      conventional or liposomal amphotericin B, paromomycin and miltefosine.
      Coinfection with human immunodeficiency virus (HIV) is increasingly reported and
      comes with additional diagnostic and therapeutic challenges. This article
      provides an up-to-date clinical review of VL focusing on clinical presentation,
      diagnosis, management, and issues related to HIV coinfection.

PMID- 22632642
TI  - Protozoan infections of the gastrointestinal tract.
AB  - The review provides current views on human protozoan parasites of the gut. The
      recognition of the importance of cryptosporidium, cyclospora and microsporidia
      over the last three decades emphasises the possibility that more pathogenic
      intestinal protozoa are presently unrecognized. Each of these is a zoonotic
      infection and the potential for a zoonotic element to the transmission of
      giardiasis has been recognized. A common theme in increased understanding of the
      biology and pathological mechanisms involved in causing disease is the
      application of molecular techniques to the various stages of the parasite life
      cycle. Molecular methods are increasingly contributing to laboratory diagnosis of
      these conditions with increased yields of positive results though in the tropics
      it is likely that fecal microscopy will remain the standard for some time to
      come. The nitroimidazole compounds are the mainstay of treatment for giardia and
      amebiasis with no major advance in therapeutics since their role was appreciated.
      Nitazoxanide was shown to be effective for cryptosporidiosis in the 1990s.

PMID- 22632643
TI  - Nematode infections: soil-transmitted helminths and trichinella.
AB  - Infection with soil-transmitted helminths occurs via ingestion of nematode eggs
      with contaminated food and water, via hands, or inhalation of dust, or by
      penetration of larvae through the skin. Trichinella infections are caused by the
      ingestion of larvae contained in undercooked meat. In highly endemic areas,
      preventive chemotherapy (ie, regular administration of anthelmintic drugs to at
      risk populations) is the key strategy against soil-transmitted helminthiasis.
      Integrated control approaches, including improved hygiene, sanitation, and water,
      are required for lasting effects. Because of growing tourism, travel, and
      migration, clinicians and specialized travel clinics must remain aware of the
      diagnosis, prevention, and treatment of soil-transmitted helminth and Trichinella
      infections.

PMID- 22632644
TI  - Nematode infections: filariases.
AB  - More than 150 million people, mainly in developing countries, are affected by
      filarial nematode infections that cause debilitating and disfiguring diseases.
      Although transmission is restricted to the tropics and subtropics, imported
      infections sometimes occur in Europe and North America among immigrants and
      refugees from endemic countries, and rarely among long-term travelers. This
      article reviews the epidemiology of the most important human filarial nematodes,
      their current distribution, life cycles, clinical features, and disease burden.
      Diagnosis, treatment, and tools for prevention and control are discussed.
      Protective measures for travelers are summarized, and vulnerable groups and case
      numbers in North America identified.

PMID- 22632645
TI  - Schistosomiasis.
AB  - Schistosomiasis is a tropical parasitic disease, caused by blood-dwelling worms
      of the genus Schistosoma. The main human species are S mansoni (occurring in
      Africa and South America) and S japonicum (South and East Asia) causing
      intestinal and hepatosplenic schistosomiasis, and S haematobium (Africa) causing
      urinary schistosomiasis. Severe symptoms develop in predilected people with heavy
      and long-standing infections. Acute schistosomiasis, a flulike syndrome, is a
      regular finding in travel clinics. Although prevalences can be high, most
      infected people show limited, intermittent, or aspecific symptoms. The diagnosis
      of schistosomiasis relies on microscopic examination of stools or urine,
      serologic tests, and imaging. Praziquantel is the drug of choice, active against
      all species in a single or a few oral doses. Current control strategies consist
      mainly of preventive therapy in communities or groups at risk.

PMID- 22632646
TI  - Trematode infections: liver and lung flukes.
AB  - Food-borne trematodiases are an emerging public health problem in Southeast Asia
      and Latin America and of growing importance for travel clinics in Europe and
      North America. The disease is caused by chronic infections with liver, lung, and
      intestinal flukes. This article focuses on the most important liver and lung
      flukes that parasitize man, namely Clonorchis sinensis, Fasciola gigantica,
      Fasciola hepatica, Opisthorchis felineus, Opisthorchis viverrini, and Paragonimus
      spp. The article describes the epidemiology of major liver and lung fluke
      infections, including current distribution, burden, life cycle, clinical signs
      and symptoms, diagnostic approaches, and current tools for prevention, treatment,
      and control.

PMID- 22632647
TI  - Cestode infestations: hydatid disease and cysticercosis.
AB  - Although humans can be definitive hosts for cestodes (tapeworms), major
      pathologic conditions occur during cestode larval stages when humans serve as the
      intermediate host for these parasites. The most relevant forms of human disease
      caused by cestode larvae are echinococcosis, caused by Echinococcus granulosus
      (cystic echinococcosis) and Echinococcus multilocularis (alveolar
      echinococcosis), and cysticercosis, caused by Taenia solium. These infections
      occur worldwide, but their relevance is particularly high in developing
      countries, where poor hygiene conditions facilitate the transmission of the
      parasites. The therapeutic approach is often complex, requiring surgery and/or
      chemotherapy or, in the case of cystic echinococcosis, percutaneous treatments.

PMID- 22632648
TI  - Tropical bacterial gastrointestinal infections.
AB  - The bacterial gastrointestinal infections cholera, salmonellosis, shigellosis,
      campylobacteriosis, and diarrheagenic Escherichia coli are prevalent in tropical
      regions. These diseases impose an immense cost and contribute significantly to
      childhood morbidity and mortality. Management is hampered by limited access to
      diagnostic facilities and by antimicrobial drug resistance. Rapid point-of-care
      assays aim to reduce treatment delay and encourage rational use of antimicrobial
      agents. Control through safe drinking water, good sanitation, and vaccination
      against typhoid and cholera in high-risk populations is recommended. Vaccines
      against other Shigella and diarrheagenic E coli infections are under development.

PMID- 22632649
TI  - Vector-borne rickettsioses in North Africa.
AB  - The purpose of this article is to overview vector-borne rickettsioses in North
      Africa, focusing on epidemiologic aspects, clinical features, diagnosis
      procedures, and treatment. The protective measures, the exposure to risk, and the
      dynamics of endemic emerging and re-emerging diseases in the region are detailed
      to minimize the risk when traveling in this area. In addition, the article
      describes the scientific contribution on the rickettsial field of North-African
      researchers from the beginning of the 20th century until today.

PMID- 22632650
TI  - Arboviruses and viral hemorrhagic fevers (VHF).
AB  - The viral hemorrhagic fever (VHF) syndrome is a potentially life-threatening
      infection typified by a combination of a capillary leak syndrome and bleeding
      diathesis. Most but not all agents causing VHF are arboviruses, with transmission
      to humans resulting from an arthropod bite. Agents of VHF affect humans on all
      continents. Population growth, urbanization, human activities, and even climate
      change all contribute to a continual flux in the epidemiology of many
      arboviruses. This review provides an overview of the epidemiology of arboviral
      infections and VHF, the main clinical syndromes, and their diagnosis and
      treatment.

PMID- 22632651
TI  - Tropical fungal infections.
AB  - Fungal infections are more common and diverse in the tropics but are also
      increasingly seen in returning travelers and migrants as international travel
      becomes easier. They are conventionally classified into superficial, cutaneous,
      subcutaneous, and systemic mycoses. This article provides an overview of
      superficial, cutaneous, and subcutaneous mycoses that are more prevalent and/or
      geographically restricted to the tropics and briefly discusses fungal infections
      in returning travelers. Systematic data on such infections as travel-associated
      diseases are currently lacking, and enhanced surveillance for fungal infections
      may lead to early diagnosis and an understanding of the epidemiology of the
      fungal infections among travelers.

PMID- 22632652
TI  - Laboratory diagnosis of tropical infections.
AB  - This article covers the laboratory diagnosis of infections that occur
      predominantly in the tropics. The discussion includes diagnosis of blood and
      tissue parasites, intestinal parasites, and tropical infections caused by fungi,
      bacteria, and mycobacteria. The laboratory performance of techniques for the
      identification of intestinal parasites and special requirements for the
      collection of specimens for virology testing are also discussed. Images
      demonstrating the characteristic features of selected tropical parasites and
      fungi are included for reference.

PMID- 22632653
TI  - Preface: tropical diseases.

PMID- 22632654
TI  - Is inferior mesenteric artery ligation during sigmoid colectomy for diverticular
      disease associated with increased anastomotic leakage? A meta-analysis of
      randomized and non-randomized clinical trials.
AB  - AIM: A meta-analysis was conducted to compare preservation with ligation of the
      inferior mesenteric artery (IMA) during sigmoidectomy for diverticular disease.
      METHOD: Randomized and non-randomized clinical trials were identified using the
      following electronic databases: Medline, Embase, Cochrane Central Register of
      Controlled Trials, CINAHL, BioMed Central, Science Citation Index, Greynet,
      SIGLE, National Technological Information Service, British Library Integrated
      Catalogue. The analysed end-points were the anastomotic leakage rate, overall
      morbidity and 30-day postoperative mortality. RESULTS: Four studies were included
      involving 400 patients. The anastomotic leakage rate was 7.3% in the preservation
      group and 11.3% in the ligation group. There was no statistically significant
      difference between the groups (OR 0.72, 95% CI 0.11-4.76; P=0.73). Overall
      morbidity and 30-day postoperative mortality were not compared since these data
      were reported in only one study. CONCLUSION: The meta-analysis did not show any
      advantage for preservation of the IMA during sigmoid colectomy for diverticular
      disease in terms of anastomotic leakage.

PMID- 22632655
TI  - Corrupted cultures in mental health inpatient settings. Is restraint reduction
      the answer?
AB  - The early years of the 21st century have seen successful efforts in a number of
      countries to reduce the use of restraint in services for people with mental
      health problems. An underlying emphasis on 'cultural change' is characteristic of
      such initiatives reflecting, it appears, the re-emergence of interest in the
      therapeutic milieu. Such efforts have though lacked a comprehensive explanation
      of how organizational culture plays a role in the development of the excessive
      use of restraint, which seems to respond to such initiatives. This paper seeks to
      address that deficit and draws in particular on the concepts of corrupted
      culture, institutional violence, trauma, parallel processing and contemporary
      research on restraint and seclusion reduction. In doing so it examines whether
      restraint reduction initiatives represent part of the solution to the problem of
      corruption, which is intrinsically associated with the legitimatization of
      coercion.

PMID- 22632657
TI  - Communication--are we listening?

PMID- 22632656
TI  - The total synthesis of (-)-aurafuron A.
AB  - The first total synthesis of (-)-aurafuron A is presented. It features a Suzuki
      cross-coupling reaction and a high yielding anionic aldol addition as central
      carbon skeleton building reactions. The synthesis confirms the proposed structure
      including its configuration and allows for detailed SAR studies.

PMID- 22632658
TI  - It hurts more when it's you.

PMID- 22632659
TI  - The ABR "recalls" conundrum: an ethical quandary.

PMID- 22632660
TI  - The financial crisis: professional lessons for physicians.

PMID- 22632661
TI  - Checklists: from the cockpit to the radiology department.

PMID- 22632662
TI  - The measures of success.

PMID- 22632663
TI  - Sustainability, or how I learned to stop worrying and love the photons.

PMID- 22632664
TI  - Capturing the cognitive input of radiologists in the care process: next
      generation health IT requirements.

PMID- 22632665
TI  - ACR Appropriateness Criteria(r) pretreatment planning of invasive cancer of the
      cervix.
AB  - The prognosis of cervical cancer is linked to lymph node involvement, and this is
      predicted clinically and pathologically by the stage of the disease, as well as
      the volume and grade of the tumor. Staging of cervical cancer based on
      International Federation of Gynecology and Obstetrics (FIGO) staging uses
      physical examination, cystoscopy, proctoscopy, intravenous urography, and barium
      enema. It does not include CT or MRI. Evaluation of the parametrium is limited in
      FIGO staging, and lymph node metastasis, an important prognostic factor, is not
      included in FIGO staging. The most important role for imaging is to distinguish
      stages Ia, Ib, and IIa disease treated with surgery from advanced disease treated
      with radiation therapy with or without chemotherapy. This article reviews the
      current role of imaging in pretreatment planning of invasive cervical cancer. The
      ACR Appropriateness Criteria((r)) 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 in which evidence is lacking or not definitive, expert opinion may be
      used to recommend imaging or treatment.

PMID- 22632666
TI  - Physician documentation deficiencies in abdominal ultrasound reports: frequency,
      characteristics, and financial impact.
AB  - PURPOSE: The aim of this study was to assess the frequency, characteristics, and
      financial impact of physician documentation deficiencies in abdominal ultrasound
      reports. METHODS: Using a multi-institutional coding and billing database and
      natural language processing software, 12,699,502 radiology reports from 37
      practices were used to identify and analyze abdominal ultrasound reports. Using
      standard Current Procedural Terminology((r)) (CPT((r))) criteria, examinations
      were categorized as complete (all 8 required elements documented) or limited (<8
      elements). Assuming incomplete documentation, examinations were categorized as
      very likely, likely, or possibly complete depending on whether a minimum of 7, 6,
      or 5 elements were reported. Frequency and financial impact were assessed using
      all 3 models, and presumed documentation deficiencies were characterized.
      RESULTS: Of 336,062 abdominal ultrasound reports by 1,136 radiologists, 252,478
      (75.1%) documented all 8 elements for CPT coding as complete examinations, 25,925
      (7.7%) documented 7 elements, 20,559 (5.6%) documented 6 elements, 17,521 (4.8%)
      documented 5 elements, and 49,579 (13.5%) documented <=4 elements. For very
      likely, likely, and possibly complete examination models, deficiencies were
      present in 9.3%, 15.5%, and 20.2% of cases, resulting in 2.5%, 4.2%, and 5.5%
      decreases in legitimate professional payments. The spleen (41.2%) was the most
      frequent element neglected. Of 106,168 examinations titled complete, only 92,824
      (87.4%) fulfilled complete CPT criteria. In 221,887 (60.6%), examination titles
      were clearly erroneous or too ambiguous for code assignment. Documentation
      deficiencies were less frequent for high-volume radiologists (P < .0001).
      CONCLUSIONS: Incomplete physician documentation in abdominal ultrasound reports
      is common (9.3%-20.2% of cases) and results in 2.5% to 5.5% in lost professional
      income. Structured reporting may improve documentation and mitigate lost revenue.

PMID- 22632667
TI  - Emergency department CT of the abdomen and pelvis: preferential utilization in
      higher complexity patient encounters.
AB  - PURPOSE: The aim of this study was to assess the association of patient encounter
      complexity and the utilization of CT of the abdomen and pelvis (CTAP) in the
      emergency department (ED) setting. METHODS: Using 5% research identifiable files
      for 2007, ED visits for Medicare fee-for-service beneficiaries were identified.
      Contemporaneous ED physician evaluation and management codes were used as the
      basis for patient complexity categorization. Encounters in which CTAP was
      performed on the same date of service were identified, and variables affecting
      the utilization of CTAP were analyzed. RESULTS: Of 1,081,000 ED encounters,
      306,401 (28.3%) were of lower complexity and 774,599 (71.7%) were of higher
      complexity. CT of the abdomen and pelvis was performed in 65,273 of all
      encounters (6.0%), corresponding to 4,069 (1.3%) of lower complexity and 61,204
      (7.9%) of higher complexity encounters (odds ratio, 5.95; 95% confidence
      interval, 5.76-6.14). Of the 65,273 ED encounters associated with CTAP, 61,204
      (93.8%) were of higher complexity. CONCLUSIONS: Of patients undergoing CTAP in
      the ED setting, a very large majority (93.8%) are clinically complex. CT of the
      abdomen and pelvis is 5.95 times more likely to be utilized in higher than lower
      complexity ED patient encounters.

PMID- 22632668
TI  - Large-scale automated assessment of radiologist adherence to the Physician
      Quality Reporting System for stroke.
AB  - PURPOSE: Physician Quality Reporting System (PQRS) measure 10 assesses the
      percentage of radiology reports for possible stroke that document the presence or
      absence of hemorrhage, mass, and acute infarction. Although it is an important
      report quality metric, determining adherence to this measure is often laborious,
      limiting its practical use. The aim of this study was to assess adherence to PQRS
      measure 10 using an automated approach to facilitate continuous measurement. A
      secondary goal was to identify explanatory variables that may affect adherence.
      METHODS: To determine measure adherence, a computerized algorithm was built,
      validated, and executed on 4,045 reports from CT and MRI examinations performed
      between January 2008 and October 2010 in patients with suspected stroke.
      Radiologist adherence was measured, accounting for differences in imaging
      modality, the presence of abnormalities, and trainee participation in report
      creation. RESULTS: Of 4,045 reports, 58.1% met the PQRS requirement, documenting
      all 3 components. Although the presence of infarct increased the chance of PQRS
      adherence (P < .001), the existence of hemorrhage had the opposite effect (P <
      .001). Reports that had trainee participation were more likely to be in
      accordance with PQRS standards (62% vs 47%, P < .001). After controlling for
      pertinent variables, more than 2-fold variation in individual PQRS adherence (27%
      68%) remained (P < .001). CONCLUSIONS: A considerable portion of eligible
      radiology reports do not include all components proposed by PQRS measure 10. An
      important contributor to performance gaps resides in individual physician
      variability. By automating measurement and monitoring of radiologist PQRS
      performance, informatics tools may enable targeted interventions to improve
      report quality.

PMID- 22632669
TI  - Utilization effect of integrating a chest radiography room into a thoracic
      surgery ward.
AB  - PURPOSE: Bedside chest radiography (CXR) represents a substantial fraction of the
      volume of medical imaging for inpatient health care facilities. However, its
      image quality is limited compared with posterior-anterior/lateral (PA/LAT)
      acquisitions taken in radiographic rooms. The aim of this study was to evaluate
      the utilization of bedside CXR and other chest imaging modalities before and
      after placing a radiography room within a thoracic surgical inpatient ward.
      METHODS: All patient admissions (n = 3,852) to the thoracic surgical units
      between April 1, 2007, and December 31, 2010, were retrospectively identified.
      All chest imaging tests performed for these patients, including CT scans, MRI,
      ultrasound, and bedside and PA/LAT radiography, were counted. The primary outcome
      measure was chest imaging utilization, defined as the number of chest
      examinations per admission, before and after the establishment of the digital
      radiography room on January 10, 2010. Statistical analysis was performed using an
      independent-samples t test to evaluate changes in chest imaging utilization.
      RESULTS: A 2.61-fold increase in the number of PA/LAT CXR studies per admission
      (P < .01) and a 1.96-fold decrease in the number of bedside CXR studies per
      admission (P < .01) were observed after radiography room implementation. The
      number of chest CT, MRI, and ultrasound studies per admission did not change
      significantly. CONCLUSIONS: Establishing a radiography room physically within
      thoracic surgery units or in close proximity can significantly shift CXR
      utilization from bedside to PA/LAT acquisitions, which may enable opportunities
      for improvement in efficiency, quality, and safety in patient care.

PMID- 22632670
TI  - Mobile technology in radiology resident education.
AB  - PURPOSE: The authors hypothesized that ownership of a mobile electronic device
      would result in more time spent learning radiology. Current trends in radiology
      residents' studying habits, their use of electronic and printed radiology
      learning resources, and how much of the funds allotted to them are being used
      toward printed vs electronic education tools were assessed in this study.
      METHODS: A survey study was conducted among radiology residents across the United
      States from June 13 to July 5, 2011. Program directors listed in the Association
      of Program Directors in Radiology e-mail list server received an e-mail asking
      for residents to participate in an online survey. The questionnaire consisted of
      12 questions and assessed the type of institution, the levels of training of the
      respondents, and book funds allocated to residents. It also assessed the
      residents' study habits, access to portable devices, and use of printed and
      electronic radiology resources. RESULTS: Radiology residents are adopters of new
      technologies, with 74% owning smart phones and 37% owning tablet devices.
      Respondents spend nearly an equal amount of time learning radiology from printed
      textbooks as they do from electronic resources. Eighty-one percent of respondents
      believe that they would spend more time learning radiology if provided with
      tablet devices. CONCLUSIONS: There is considerable use of online and electronic
      resources and mobile devices among the current generation of radiology residents.
      Benefits, such as more study time, may be obtained by radiology programs that
      incorporate tablet devices into the education of their residents.

PMID- 22632671
TI  - Focused peer review: the end game of peer review.
AB  - PURPOSE: The aim of this report is to describe the authors' experience with
      expanding the routine peer-review process to include misdiagnoses from all
      sources and the use of focused peer review (FPR) in faculty accountability and
      management. METHODS: A department-wide routine peer review was conducted. Each
      radiologist was assigned 12 cases per month. In addition, clinically reported
      errors, missed diagnoses discovered outside the routine peer-review process, were
      identified. Cases were scored from 1 to 5. The department quality office
      evaluated cases with scores of 3 and 4 from both sources for further processing
      with FPR, a multistep continuation of the peer-review process using a tracking
      document. Once initiated, FPR was processed by seeking comments from the division
      director and the interpreting radiologist. In some cases, FPR was discontinued
      before completion. Completed FPR documents were submitted to the department chair
      for administrative action, ranging from no action to termination. All FPR cases
      are presented at monthly departmental morbidity and mortality conferences.
      RESULTS: Routine peer review was done on 1,646 cases from a total of about
      300,000 studies by 31 radiologists. Thirty-five cases from the two sources with
      scores of 3 and 4 were analyzed, 21 from the routine peer review and 14
      clinically reported errors. The quality officer initiated 25 FPRs, rejecting 10
      because errors were not considered significant. Further scrutiny lead to dropping
      7 of the 12 routine and 2 of the 13 cases with clinically reported error. Sixteen
      FPRs were completed, 5 (31%) from routine peer review and 11 (69%) from
      clinically reported errors. For these 16 completed FPRs, management decisions
      were made by the department chair. CONCLUSIONS: Processing of routine peer-review
      data together with cases of clinically reported error strengthens the peer-review
      process. Focused peer review can effectively contribute to the surveillance and
      management of faculty performance for improved patient care.

PMID- 22632672
TI  - To text or not to text?

PMID- 22632673
TI  - Events that have shaped the quality movement in radiology.

PMID- 22632674
TI  - How to develop, submit, and get an iPad application accepted to the Apple Store.

PMID- 22632675
TI  - Technical factors for consideration in selecting a 4-D CT simulator.

PMID- 22632676
TI  - Quality in radiology: how involving residents in practice quality improvement can
      improve our specialty and invigorate the next generation of leaders.

PMID- 22632677
TI  - Edith H. Quimby.

PMID- 22632681
TI  - The Journal of Biomolecular Structure and Dynamics Establishes Web Site: The JBSD
      WWW Edition.

PMID- 22632678
TI  - Re: "Patient-centered imaging: opportunities and challenges".

PMID- 22632682
TI  - Cancer Watch Establishes Web Site: The CANCER WATCH WWW Edition.

PMID- 22632683
TI  - Tenth Conversation in the Discipline Biomolecular Stereodynamics The University,
      Albany, New York, June 17-21, 1997.

PMID- 22632685
TI  - Patterns of stranding and mortality in common seals (Phoca vitulina) and grey
      seals (Halichoerus grypus) in The Netherlands between 1979 and 2008.
AB  - Pathological examination of stranded marine mammals provides information on the
      causes of mortality in their populations. Patterns of stranding and causes of
      death of dead-stranded seals on the Dutch coast were analyzed over a 30-year
      period (1979-2008). Stranding data (n=1,286) and post-mortem data (n=379) from
      common seals (Phoca vitulina) and grey seals (Halichoerus grypus) found dead, or
      that died before admission to rehabilitation, were obtained from the Seal
      Rehabilitation and Research Centre database. Data for the years 1988 and 2002,
      when mass mortality occurred due to phocine distemper virus epidemics, were
      excluded. Common seal stranding increased from one to nearly 100 per year over
      this period. This coincides with the increase in the number of common seals in
      Dutch waters over recent decades. Grey seal stranding increased gradually from
      one to about 40 per year over the period, reflecting recolonization of Dutch
      waters by this species. For both species, the trend in stranding of dead seals
      was found to be in line with that of seals observed in Dutch waters during aerial
      surveys and did not provide any indications of a relative change in the stranding
      rate of dead seals. The total monthly stranding rates peaked at more than 120 in
      June and July for common seals and at nearly 60 in January for grey seals. This
      coincides with the pupping periods of the two species. Besides phocine distemper,
      the most common causes of death in investigated common seals (n=286) were by
      catch (confirmed and inferred) (19%), pup starvation (7%), intestinal volvulus
      (7%) and parasitic bronchopneumonia (6%). The most common causes of death in
      investigated grey seals (n=93) were by-catch (confirmed and inferred) (15%), pup
      starvation (11%) and trauma (5%). The relative occurrence of by-catch
      significantly decreased over time for grey seals, but not for common seals.
      Common seals were affected by infectious disease significantly more often than
      grey seals, mainly because of a higher occurrence of parasitic pneumonia. Phocine
      distemper caused mass mortalities among common seals, but not among grey seals.
      These findings in dead-stranded seals differ in part from those reported
      elsewhere in live-stranded seals, for which pup starvation and parasitic
      bronchopneumonia were the main causes of stranding. A substantial proportion of
      seals in Dutch waters die from causes related to human activity. Continued
      monitoring of stranding patterns and causes of death is warranted for early
      detection of changes and the possibility of taking timely management actions.

PMID- 22632684
TI  - Social-emotional behaviour in infants and toddlers with mild traumatic brain
      injury.
AB  - BACKGROUND: Paediatric head trauma is a serious health concern often leading to
      neurological, behavioural and cognitive impairments. In Estonia head trauma
      incidence is especially high in children up to 4 years. OBJECTIVE: The aim was to
      investigate young children's pre-injury social-emotional behaviour to discover
      potential risk signs for brain trauma and to study social-emotional outcome 9
      months post-injury. METHODS: Thirty-five 3-65 month old children with mild
      traumatic brain injury (MTBI) and 70 matched controls were retrospectively
      assessed with child monitoring system Ages and Stages Questionnaires: Social
      Emotional. During follow-up 27 patients and 54 controls were re-assessed after 9
      months. RESULTS: Children with MTBI showed altered social-emotional development
      already before the injury. Deficits were evident in self-regulation and autonomy.
      Age-specific social-emotional risk signs for MTBI were found. Compared to
      controls more pre-injury affective problems were seen in 12-month olds, self
      regulation, and communication difficulties in 30-month olds and autonomy
      disturbances in 60-month old children. 9 months post-injury impairments in
      autonomy and self-regulation were still present and new difficulties in
      interaction had developed. CONCLUSIONS: Childhood MTBI has a serious negative
      effect on further development of interaction skills. To prevent possible traumas,
      parents should be informed of different age-specific pre-injury social-emotional
      risk signs.

PMID- 22632686
TI  - It is the most common form of arthritis and the leading cause of disability in
      older persons, affecting an estimated 27 million adults in the United States
      alone. Introduction.

PMID- 22632687
TI  - Epidemiology of osteoarthritis and associated comorbidities.
AB  - Osteoarthritis (OA) is the most common cause of walking-related disability among
      older adults in the United States, and the prevalence and incidence of OA are
      increasing rapidly. Systemic and local risk factors for knee OA have been
      identified, and obesity and joint injury appear to be the strongest risk factors
      that are both modifiable and have the potential for substantial impact on a
      population level. The risk factors for functional decline and disability in
      persons with symptomatic OA have been examined in relatively few studies. The
      course of functional decline in persons with symptomatic OA on a population level
      is generally one of stable to slowly deteriorating function, but on an individual
      level, many patients maintain function or improve during the first 3 years of
      follow-up. Obesity stands out as one of few modifiable risk factors of OA that
      also is a potentially modifiable predictor of functional decline. Physical
      activity also appears to have a substantial protective impact on future OA
      related disability. Further epidemiologic studies and randomized controlled
      trials are needed to prioritize prevention through targeting these modifiable
      risk factors for OA and related disability.

PMID- 22632688
TI  - Regenerative injection therapy for osteoarthritis: fundamental concepts and
      evidence-based review.
AB  - Regenerative therapy involves the injection of a small volume of solution into
      multiple sites of painful ligament and tendon insertions (entheses) and adjacent
      joint spaces, with the goal of reducing pain and ostensibly promoting tissue
      repair and growth. Dextrose and platelet-rich plasma solutions have been shown to
      increase expression of growth factors in vivo and have shown promising clinical
      results in the treatment of tendinosus. In the treatment of osteoarthritis, small
      clinical trials and case series to date suggest safety, symptomatic improvement,
      and functional improvement at up to a year of follow-up; however, most of these
      studies are uncontrolled. Given the methodological limitations of clinical
      research on regenerative injections for osteoarthritis to date, this treatment
      should be considered only after execution of a comprehensive assessment and
      treatment plan, including optimization of biomechanics, weight loss,
      cardiovascular exercise, resistance training, and judicious use of more
      established topical, oral, and injectable medications.

PMID- 22632689
TI  - Use of glucosamine and chondroitin in persons with osteoarthritis.
AB  - Glucosamine and chondroitin are members of a group of dietary supplements often
      termed "complementary agents," "disease-modifying agents," or "disease-modifying
      osteoarthritis drugs" (DMOADs). They are among the best-selling dietary
      supplements in the United States. DMOADs are thought to act by affecting cytokine
      mediated pathways regulating inflammation, cartilage degradation, and immune
      responses. Given the results of recent studies, investigators have begun to
      question whether the popular combination of glucosamine and chondroitin
      alleviates disease progression or pain in people with mild to moderate knee
      osteoarthritis. Reasons proposed for the lack of benefit include incorrect
      dosing, suboptimal compound manufacture, and a lack of complete understanding of
      when and how to apply the compounds. In addition, adjuvant medications also could
      augment the therapeutic potential of these agents. Although these agents are
      considered safe, some uncommon and minor adverse effects have been reported,
      including epigastric pain or tenderness (3.5%), heartburn (2.7%), diarrhea
      (2.5%), and nausea (1%). In conclusion, although some questions have arisen about
      whether DMOADs are as effective as has been claimed, a trial should be considered
      in in selected patients with sustained refractory cases of osteoarthritis.

PMID- 22632690
TI  - Does running cause osteoarthritis in the hip or knee?
AB  - Running is an excellent activity to promote general health and well-being.
      However, running injuries are common, and concern is sometimes raised that
      running might lead to osteoarthritis in weight-bearing joints. This article
      reviews the relevant in vitro and in vivo literature that looks at possible
      associations between running and the development of osteoarthritis. Also reviewed
      is the limited literature on running barefoot and with minimalist footwear. Low-
      and moderate-volume runners appear to have no more risk of developing
      osteoarthritis than nonrunners. The existing literature is inconclusive about a
      possible association between high-volume running and the development of
      osteoarthritis. The early literature on running barefoot and running with
      minimalist footwear has primarily focused on biomechanics but has not yet focused
      on any effect on cartilage health. Experienced and beginner runners should be
      encouraged to allow the body adequate time to adapt to changes in gait
      biomechanics caused by changing footwear, which can be done by slowly increasing
      running mileage in the new footwear. Clinicians can improve the health of runners
      by encouraging appropriate treatment of musculoskeletal injuries, encouraging
      maintenance of an optimal body mass index, and correcting gait abnormalities
      caused by deficits in flexibility, strength, or motor control along the kinetic
      chain.

PMID- 22632691
TI  - Complementary and alternative medicine in osteoarthritis.
AB  - The intent of this focused clinical review is to assess the current literature on
      a variety of complementary and alternative medicine treatments for
      osteoarthritis. This review assesses acupuncture techniques, moxibustion,
      transcutaneous electrical nerve stimulation, low-level laser therapy, and
      massage. These treatment methods are growing in popularity among the general
      public. It is important that providers become aware of the existing literature
      regarding the efficacy of these alternative methods for the treatment of
      osteoarthritis to adequately respond to the inquiries of our patients.

PMID- 22632692
TI  - Minimally invasive versus conventional joint arthroplasty.
AB  - With an aging population, as well as a heightened interest in physical activity,
      the demand for surgical treatment of osteoarthritis of the knee, hip, and
      shoulder has continued to expand. This demand traditionally has been met with
      total joint replacements as the definitive treatment. However, with the
      development of newer, minimally invasive techniques, patients are being offered a
      greater variety of options for pain relief and improvement in function. These
      surgical options, varying widely from arthroscopic treatment to partial joint
      replacements, have been met with mixed results as they have been applied to the
      treatment of osteoarthritis. Although they are limited in their application and
      target population, minimally invasive procedures may greatly enhance the outcome
      of the patient, as well as prevent or delay the need for future total joint
      arthroplasty. The purpose of this article is to review minimally invasive
      surgical options for the treatment of osteoarthritis of the hip, knee, and
      shoulder. We also examine their appropriate application, limitations, clinical
      outcomes, and associated complications. A brief review of total joint
      arthroplasty for the aforementioned joints has been included to provide a
      comparison of the associated clinical outcomes and surgical complications.

PMID- 22632693
TI  - Neuromuscular prehabilitation to prevent osteoarthritis after a traumatic joint
      injury.
AB  - Post-traumatic osteoarthritis (PTOA) is a process resulting from direct forces
      applied to a joint that cause injury and degenerative changes. An estimated 12%
      of all symptomatic osteoarthritis (OA) of the hip, knee, and ankle can be
      attributed to a post-traumatic cause. Neuromuscular prehabilitation is the
      process of improving neuromuscular function to prevent development of PTOA after
      an initial traumatic joint injury. Prehabilitation strategies include restoration
      of normative movement patterns that have been altered as the result of traumatic
      injury, along with neuromuscular exercises and gait retraining to prevent the
      development of OA after an injury occurs. A review of the current literature
      shows that no studies have been performed to evaluate methods of neuromuscular
      prehabilitation to prevent PTOA after a joint injury. Instead, current research
      has focused on management strategies after knee injuries, the value of exercise
      in the management of OA, and neuromuscular exercises after total knee
      arthroplasty. Recent work in gait retraining that alters knee joint loading holds
      promise for preventing the development of PTOA after joint trauma. Future
      research should evaluate methods of neuromuscular prehabilitation strategies in
      relationship to the outcome of PTOA after joint injury.

PMID- 22632694
TI  - Nutritional interventions to prevent and treat osteoarthritis. Part I: focus on
      fatty acids and macronutrients.
AB  - Osteoarthritis (OA) is the most common cause of musculoskeletal disability in
      elderly individuals, and it places an enormous economic burden on society.
      Management of OA is primarily focused on palliative relief by using agents such
      as nonsteroidal anti-inflammatory drugs and analgesics. However, such an approach
      is limited by a narrow therapeutic focus that fails to address the progressive
      and multimodal nature of OA. Given the favorable safety profile of most
      nutritional interventions, identifying disease-modifying nutritional agents
      capable of improving symptoms and also preventing, slowing, or even reversing the
      degenerative process in OA should remain an important paradigm in translational
      and clinical research. Applying advances in nutritional science to
      musculoskeletal medicine remains challenging, given the fluid and dynamic nature
      of the field, along with a rapidly developing regulatory climate over
      manufacturing and commerce requirements. The aim of this article is to review the
      available literature on effectiveness and potential mechanism of macronutrients
      for OA, with a focus on the following: long-chain omega-3 essential fatty acids
      eicosapentaenoic acid and docosahexaenoic acid, functional omega-6 fatty acid
      gamma-linolenic acid, and macronutrient composition of background diet. There
      also is a discussion about the concept of rational polysupplementation via the
      strategic integration of multiple nutraceuticals with potential complementary
      mechanisms for improving outcomes in OA. As applied nutritional science evolves,
      it will be important to stay on the forefront of proteomics, metabolomics,
      epigenetics, and nutrigenomics, because they hold enormous potential for
      developing novel therapeutic and prognostic breakthroughs in many areas of
      medicine, including OA.

PMID- 22632695
TI  - Nutritional interventions to prevent and treat osteoarthritis. Part II: focus on
      micronutrients and supportive nutraceuticals.
AB  - Osteoarthritis (OA) is the most common cause of musculoskeletal disability in the
      elderly, and it places an enormous economic burden on society, which will remain
      a major health care challenge with an aging population. Management of OA is
      primarily focused on palliative relief using agents such as nonsteroidal anti
      inflammatory drugs (NSAID) and analgesics. However, such an approach is limited
      by a narrow therapeutic focus that fails to address the progressive and
      multimodal nature of OA. Given the favorable safety profile of most nutritional
      interventions, identifying disease-modifying pharmaconutrients capable of
      improving symptoms and also preventing, slowing, or even reversing the
      degenerative process in OA should remain an important paradigm in translational
      and clinical research. The goals of pharmaconutrition for metabolic optimization
      are to drive biochemical reactions in a desired direction and to meet health
      condition-specific metabolic demands. Applying advances in nutritional science to
      musculoskeletal medicine remains challenging, given the fluid and dynamic nature
      of the field, along with a rapidly developing regulatory climate over
      manufacturing and commerce requirements. The purpose of this article is to review
      the available literature on effectiveness and potential mechanism for OA of
      micronutrient vitamins; minerals; glycosaminoglycans; avocado-soybean
      unsaponifiable fractions; methylsulfonylmethane; s-adenosylmethionine;
      undenatured and hydrolyzed collagen preparations; phytoflavonoid compounds found
      in fruits, vegetables, spices, teas, and nuts; and other nutrients on the
      horizon. There also is a discussion on the concept of rational
      polysupplementation via the strategic integration of multiple nutraceuticals with
      potential complementary mechanisms for improving outcomes in OA. As applied
      nutritional science evolves, it will be important to stay on the forefront of
      proteomics, metabolomics, epigenetics, and nutrigenomics, because they hold
      enormous potential for developing novel therapeutic and prognostic breakthroughs
      in many areas of medicine, including OA.

PMID- 22632696
TI  - Role of sex hormones in the development of osteoarthritis.
AB  - Women older than 50 years have a considerably higher prevalence of osteoarthritis
      than men of the same age group. Although several factors have been proposed,
      there is some evidence that sex hormones influence the development of
      osteoarthritis. This article will focus on the basic science and clinical
      evidence that describe the current state of knowledge regarding the relationship
      between sex hormones and the development of osteoarthritis.

PMID- 22632697
TI  - Conclusion.

PMID- 22632698
TI  - Osteoarthritis in the disabled population: a mechanical perspective.
AB  - Primary disabling conditions, such as amputation, not only limit mobility, but
      also predispose individuals to secondary musculoskeletal impairments, such as
      osteoarthritis (OA) of the intact limb joints, that can result in additive
      disability. Altered gait biomechanics that cause increased loading of the intact
      limb have been suggested as a cause of the increased prevalence of intact limb
      knee and hip osteoarthritis in this population. Optimizing socket fit and
      prosthetic alignment, as well as developing and prescribing prosthetic feet with
      improved push-off characteristics, can lead to reduced asymmetric loading of the
      intact limb and therefore are potential strategies to prevent and treat
      osteoarthritis in the amputee population. Research on disabled populations
      associated with altered biomechanics offers an opportunity to focus on the
      mechanical risk factors associated with this condition. Continued research into
      the causes of secondary disability and the development of preventive strategies
      are critical to enable optimal rehabilitation practices to maximize function and
      quality of life in patients with disabilities.

PMID- 22632699
TI  - Spine osteoarthritis.
AB  - Osteoarthritis of the spine develops as a consequence of the natural aging
      process and is associated with significant morbidity and health care
      expenditures. Effective diagnosis and treatment of the resultant pathologic
      conditions can be clinically challenging. Recent evidence has emerged to aid the
      investigating clinician in formulating an accurate diagnosis and in implementing
      a successful treatment algorithm. This article details the degenerative cascade
      that results in the osteoarthritic spine, reviews prevalence data for common
      painful spinal disorders, and discusses evidence-based treatment options for
      management of zygapophysial and sacroiliac joint arthrosis.

PMID- 22632700
TI  - The pathophysiology of osteoarthritis: a mechanical perspective on the knee
      joint.
AB  - Osteoarthritis (OA) is the most frequent cause of disability in the United
      States, with the medial compartment of the knee being most commonly affected. The
      initiation and progression of knee OA is influenced by many factors, including
      kinematics. In response to loading during weight-bearing activity, cartilage in
      healthy knees demonstrates spatial adaptations in morphology and mechanical
      properties. These adaptations allow certain regions of the cartilage to respond
      to loading; other regions are less well suited to accommodate loading.
      Alterations in normal knee kinematics shift loading from cartilage regions
      adapted for loading to regions less well suited for loading, which leads to the
      initiation and progression of degenerative processes consistent with knee OA.
      Kinematic variables that are associated with the development, progression, and
      severity of knee OA are the adduction moment and tibiofemoral rotation. Because
      of its strong correlation with disease progression and pain, the peak adduction
      moment during gait has been identified as a target for treatment design. Gait
      modification offers a noninvasive option for seeking significant reductions. Gait
      modification has the potential to reduce pain and slow the progression of medial
      compartment knee OA.

PMID- 22632701
TI  - Aerobic activity in prevention and symptom control of osteoarthritis.
AB  - Almost 27 million adults in the United States experience some form of
      osteoarthritis (OA). An epidemic of arthritis-associated disability is expected
      in the United States during the next 2 decades, largely fueled by the aging
      population and the tremendous growth in the prevalence of knee OA. Regular
      physical activity (PA), particularly strengthening and aerobic activity, can
      reduce pain and improve function and health status among patients with knee and
      hip OA. The focus of this review is on the impact of aerobic activity on the
      progression and symptom control of OA. In general, both strengthening and aerobic
      exercise are associated with improvements in pain, perceived physical function,
      and performance measures for persons with lower limb OA, although comparisons of
      strengthening versus aerobic exercise on these outcomes are unusual. Structural
      disease progression in persons with established OA has been directly evaluated by
      a limited number of PA clinical trials for persons with knee OA, but these
      protocols focused on strength training exclusively. In healthy subjects, it
      appears that overall PA is beneficial, rather than detrimental, to knee joint
      health. Possibly the most important reason for engaging in PA is to prevent
      obesity, which independently has been associated with many serious chronic
      diseases, including the incidence and progression of OA. More research is needed
      to determine the optimal types and dosing of aerobic conditioning.

PMID- 22632702
TI  - Resistance exercise for knee osteoarthritis.
AB  - The initiation, progression, and severity of knee osteoarthritis (OA) have been
      associated with decreased muscular strength and alterations in joint
      biomechanics. Chronic OA pain may lead to anxiety, depression, fear of movement,
      and poor psychological outlook. The fear of movement may prevent participation in
      exercise and social events, which could lead to further physical and social
      isolation. Resistance exercise (RX) has been shown to be an effective
      intervention both for decreasing pain and improving physical function and self
      efficacy. RX may restore muscle strength and joint mechanics while improving
      physical function. RX also may normalize muscle firing patterns and joint
      biomechanics, leading to reductions in joint pain and cartilage degradation.
      These physical adaptations could lead to improved self-efficacy and decreased
      anxiety and depression. RX can be prescribed and performed by patients across the
      spectrum of OA severity. When designing and implementing an RX program for a
      patient with knee OA, one should consider both the degree of OA severity and the
      level of pain. RX, either in the home or at a fitness facility, is an important
      component of a comprehensive regimen designed to offset the physical and
      psychological limitations associated with knee OA. Unique considerations for this
      population include (1) monitoring pain during and after exercise, (2) providing
      days of rest when disease flares occur, and (3) infusing variety into the
      exercise regimen to encourage adherence.

PMID- 22632703
TI  - Physical therapy in persons with osteoarthritis.
AB  - Osteoarthritis (OA) is a leading cause of musculoskeletal pain and disability.
      According to a study by Lawrence et al, an estimated 27 million Americans were
      living with OA in 2008. This number will continue to increase as the population
      of persons older than 65 years grows. Because of the increasing number of persons
      who have this chronic condition that causes pain and decreases function, the
      prevalence of this diagnosis in primary care and musculoskeletal clinics likely
      will increase. The reduction of pain and improvement in function should be goals
      of providers who treat these patients. Physical therapy (PT) is a commonly used
      treatment modality for persons with OA. Many treatment modalities are available
      within the scope of PT, including strength training, manual therapy, aquatic
      therapy, electrical stimulation, and balance and perturbation training. A review
      of the most recent and highest-quality literature regarding these modalities
      found that strength training, aquatic therapy, and balance and perturbation
      therapy were the most beneficial with respect to reducing pain and improving
      function. Evidence clearly indicates that electrical stimulation likely has very
      little impact on these variables, and evidence regarding manual therapy is
      equivocal. Literature reviewing prognostic indicators for persons with OA who
      will likely respond to PT reveal that persons with milder disease (ie, unilateral
      OA, symptoms for less than 1 year, and a 40-m self-paced walking test of less
      than 25.9 seconds) and those who have pain of 6 or greater on the numerical pain
      rating scale are likely to have better outcomes with PT, which suggests that
      earlier referral is preferable. Barriers to the acceptance of PT as a therapeutic
      treatment for OA include fatalistic patient and provider perspectives, inadequate
      analgesia, and a fear among some patients and providers that increased activity
      will lead to progression of their OA.

PMID- 22632705
TI  - Imaging techniques in osteoarthritis.
AB  - Osteoarthritis is the most common form of arthritis and is one of the leading
      causes of disability in older adults. The measures of disease progression
      currently being used to better understand the disease pathogenesis and to measure
      structural change in clinical trials are most clearly documented in late stages
      of disease and not early in the disease process, when intervention may be more
      effective. A large number of epidemiologic and clinical trials currently are
      underway to identify the most valid and responsive set of end points. Recent
      studies have provided unique insights into the relationship between the structure
      identified on imaging and symptom and disease genesis. The purpose of this
      narrative review is to briefly consider radiographic developments, appraise the
      developments in magnetic resonance imaging as it pertains to osteoarthritis, and
      suggest potential areas for further development.

PMID- 22632704
TI  - Obesity and weight loss in the treatment and prevention of osteoarthritis.
AB  - Obesity is associated with an increasing prevalence of musculoskeletal complaints
      and pain. Obesity is a major risk factor for osteoarthritis (OA), and pain can
      manifest in load-bearing and nonload-bearing joints. The lumbar spine and the
      knee are 2 primary sites for pain onset in the obese patient. Irrespective of the
      weight loss method, reduction of body fat can lower the mechanical and
      inflammatory stressors that contribute to OA. Single or combined methods of
      weight loss including exercise, dietary modification, medications, and bariatric
      surgery are associated with lower joint pain and increased physical function.
      Methods of weight loss or maintenance in early years may reduce the life exposure
      of joints to the obesity induced stressors on load bearing joints.

PMID- 22632706
TI  - Injectable medications for osteoarthritis.
AB  - Osteoarthritis is one of the most frequent and chronic conditions that affect the
      U.S. population. Use of intra-articular injections is one of the established
      treatment options available in the nonoperative care for the management of
      symptomatic osteoarthritis. Common injectable medications include
      corticosteroids, hyaluronic acid, and other less traditional compounds (for
      example, botulinum toxin). Corticosteroids work by anti-inflammatory and
      antinociceptive actions. Corticosteroids have been shown to decrease pain and
      symptoms associated with osteoarthritis for up to 3 weeks. Hyaluronic acid has an
      unclear mechanism of action, but it is thought to promote the restoration of
      hyaluronic acid within an osteoarthritic joint. The efficacy of hyaluronic acid
      is modest and is most beneficial between 5 and 13 weeks after treatment. Other
      injectable compounds have been studied and include botulinum toxin type A, which
      has been theorized to work as an antinociceptive agent. One must be aware of the
      potential adverse effects associated with these medications. For all of these
      injectable treatments, the placebo effect must not be overlooked, because it has
      be demonstrated in multiple studies that these medications provide similar relief
      of pain when compared with placebo. Image guidance with ultrasound or fluoroscopy
      may be considered when performing intra-articular injections to improve accurate
      placement of medication.

PMID- 22632707
TI  - Pharmaceutical therapy for osteoarthritis.
AB  - There are a variety of oral and topical pharmaceutical agents for the treatment
      of osteoarthritis. To date there is no pharmacologic agent proved to prevent
      disease progression. This article focuses primarily on the medications used for
      symptomatic relief and palliation of pain. The article reviews the medications'
      mechanisms of action and the available efficacy literature, as well as
      indications, contraindications, and common adverse effects.

PMID- 22632708
TI  - Bracing and orthoses: a review of efficacy and mechanical effects for
      tibiofemoral osteoarthritis.
AB  - The knee is the weight-bearing joint most commonly affected by osteoarthritis.
      Bracing of the knee or the foot can be a useful nonoperative and nonpharmacologic
      treatment for persons with osteoarthritis that predominantly involves either the
      medial or lateral tibiofemoral compartment. The aim of wedged insoles and
      realigning knee braces is to reduce articular contact stress in the more involved
      tibiofemoral compartment. There is evidence that even knee sleeves that do not
      have an effect on alignment may confer symptomatic relief and enhance joint
      position sense. This review summarizes the current state of knowledge regarding
      the degree to which bracing at the knee or foot can effectively correct
      tibiofemoral malalignment, improve knee joint pain, and enhance physical
      function, and provides clinical recommendations for prescription of these devices
      to optimize effectiveness.

PMID- 22632709
TI  - Total joint arthroplasty for persons with osteoarthritis.
AB  - Osteoarthritis is a process largely associated with aging, and Americans today
      are living longer than ever before, with the most recent data from the Centers
      for Disease Control and Prevention showing an average life expectancy of 78.2
      years. With an increasingly older society, there will be an increased need for
      medical and surgical treatment of osteoarthritis. At the same time, a decline in
      the number of surgeons performing total joint arthroplasty is anticipated, by as
      much as 30% in some studies. Due to this anticipated shortage, nonoperative
      physicians will play a more prominent role in patient care and should become
      better educated in maximizing nonoperative care, recognizing appropriate surgical
      indications, and educating their patients on surgical outcomes. Total joint
      arthroplasty offers pain relief and potential functional improvement.
      Unfortunately, the outcomes for joint replacement differ significantly by the
      joint being replaced. The best examples of positive outcome for both pain relief
      and functional improvement are total hip arthroplasty and total knee
      arthroplasty. Shoulder arthroplasty has demonstrated encouraging outcomes but the
      outcome data is not yet as robust as the data for hip and knee arthroplasty.
      Elbow arthroplasty provides good pain relief but functional outcomes are not
      nearly as good, and significant potential complications exist. Lastly, ankle
      arthroplasty has not demonstrated outcomes that are as positive as the other
      major joints, and the criterion standard treatment continues to be ankle fusion.
      In this article, surgical options for arthroplasty will be reviewed for each of
      the major joints, including the joint-specific indications and outcomes for each
      procedure.

PMID- 22632710
TI  - Mathematical modeling of tumor growth and tumor growth inhibition in oncology
      drug development.
AB  - INTRODUCTION: Approaches aiming to model the time course of tumor growth and
      tumor growth inhibition following a therapeutic intervention have recently been
      proposed for supporting decision making in oncology drug development. When
      considered in a comprehensive model-based approach, tumor growth can be included
      in the cascade of quantitative and causally related markers that lead to the
      prediction of survival, the final clinical response. AREAS COVERED: The authors
      examine articles dealing with the modeling of tumor growth and tumor growth
      inhibition in both preclinical and clinical settings. In addition, the authors
      review models describing how pharmacological markers can be used to predict tumor
      growth and models describing how tumor growth can be linked to survival
      endpoints. EXPERT OPINION: Approaches and success stories of application of model
      based drug development centered on tumor growth modeling are growing. It is also
      apparent that these approaches can answer practical questions on drug development
      more effectively than that in the past. For modeling purposes, some improvements
      are still needed related to study design and data quality. Further efforts are
      needed to encourage the mind shift from a simple description of data to the
      prediction of untested conditions that modeling approaches allow.

PMID- 22632711
TI  - Severe asthma and allergy: mechanisms, diagnostics and treatment.

PMID- 22632712
TI  - DNA-based hybridization chain reaction for amplified bioelectronic signal and
      ultrasensitive detection of proteins.
AB  - This work reports a novel electrochemical immunoassay protocol with signal
      amplification for determination of proteins (human IgG here used as a model
      target analyte) at an ultralow concentration using DNA-based hybridization chain
      reaction (HCR). The immuno-HCR assay consists of magnetic immunosensing probes,
      nanogold-labeled signal probes conjugated with the DNA initiator strands, and two
      different hairpin DNA molecules. The signal is amplified by the labeled ferrocene
      on the hairpin probes. In the presence of target IgG, the sandwiched
      immunocomplex can be formed between the immobilized antibodies on the magnetic
      beads and the signal antibodies on the gold nanoparticles. The carried DNA
      initiator strands open the hairpin DNA structures in sequence and propagate a
      chain reaction of hybridization events between two alternating hairpins to form a
      nicked double-helix. Numerous ferrocene molecules are formed on the neighboring
      probe, each of which produces an electrochemical signal within the applied
      potentials. Under optimal conditions, the immuno-HCR assay presents good
      electrochemical responses for determination of target IgG at a concentration as
      low as 0.1 fg mL(-1). Importantly, the methodology can be further extended to the
      detection of other proteins or biomarkers.

PMID- 22632713
TI  - Comparative multi-omics systems analysis of Escherichia coli strains B and K-12.
AB  - BACKGROUND: Elucidation of a genotype-phenotype relationship is critical to
      understand an organism at the whole-system level. Here, we demonstrate that
      comparative analyses of multi-omics data combined with a computational modeling
      approach provide a framework for elucidating the phenotypic characteristics of
      organisms whose genomes are sequenced. RESULTS: We present a comprehensive
      analysis of genome-wide measurements incorporating multifaceted holistic data -
      genome, transcriptome, proteome, and phenome - to determine the differences
      between Escherichia coli B and K-12 strains. A genome-scale metabolic network of
      E. coli B was reconstructed and used to identify genetic bases of the phenotypes
      unique to B compared with K-12 through in silico complementation testing. This
      systems analysis revealed that E. coli B is well-suited for production of
      recombinant proteins due to a greater capacity for amino acid biosynthesis, fewer
      proteases, and lack of flagella. Furthermore, E. coli B has an additional type II
      secretion system and a different cell wall and outer membrane composition
      predicted to be more favorable for protein secretion. In contrast, E. coli K-12
      showed a higher expression of heat shock genes and was less susceptible to
      certain stress conditions. CONCLUSIONS: This integrative systems approach
      provides a high-resolution system-wide view and insights into why two closely
      related strains of E. coli, B and K-12, manifest distinct phenotypes. Therefore,
      systematic understanding of cellular physiology and metabolism of the strains is
      essential not only to determine culture conditions but also to design recombinant
      hosts.

PMID- 22632714
TI  - Supporting children whose parent has a mental health problem: an assessment of
      the education, knowledge, confidence and practices of registered psychiatric
      nurses in Ireland.
AB  - Health professionals, including nurses, stand accused of ignorance or oversight
      of children whose parent experience a mental health problem. Psychiatric nurses
      are in an ideal position to respond to children's needs and support their parents
      in a proactive and sensitive manner. The aim of this study was to explore
      psychiatric nurses' education, knowledge, confidence and practice with regard to
      the support needs of children whose parent has a mental health problem. This
      study employed a self-completion anonymous survey design with a sample of
      registered psychiatric nurses from one integrated mental health service in
      Ireland. The sample reported relatively low levels of education, knowledge,
      confidence and supportive clinical practice when it came to children whose parent
      has a mental health problem. There is an urgent need for education on family
      focused care, and the development of guidelines and child focused services if the
      needs of parents and children are to be met.

PMID- 22632715
TI  - Human adult olfactory bulb neurogenesis? Novelty is the best policy.
AB  - There is ongoing controversy as to whether the understanding of adult mammalian
      neurogenesis gained from rodent studies is applicable to humans. In this issue of
      Neuron, Bergmann et al. (2012) propose that adult human olfactory bulb
      neurogenesis with long-term neuronal survival is extremely limited.

PMID- 22632716
TI  - Complement-mediated microglial clearance of developing retinal ganglion cell
      axons.
AB  - In many parts of the developing vertebrate nervous system, axons are pruned to
      establish mature patterns of connectivity. In this issue of Neuron, Schafer et
      al. (2012) show that microglia may play a role in developmental axon pruning in
      the thalamus by engulfing presynaptic retinal ganglion cell terminals via a C3-
      and CR3-dependent mechanism.

PMID- 22632717
TI  - In epilepsy, BAD is not really bad.
AB  - In this issue of Neuron, Gimenez-Cassina et al. (2012) show that fuel utilization
      by neuronal mitochondria, controlled by the Bcl-2 family member BAD, defines
      response to seizures. Control of K(ATP) channels by mitochondrial metabolism
      might be a target for antiepileptic therapies.

PMID- 22632718
TI  - Data visualization in the neurosciences: overcoming the curse of dimensionality.
AB  - In publications, presentations, and popular media, scientific results are
      predominantly communicated through graphs. But are these figures clear and honest
      or misleading? We examine current practices in data visualization and discuss
      improvements, advocating design choices which reveal data rather than hide it.

PMID- 22632719
TI  - How we feel: ion channel partnerships that detect mechanical inputs and give rise
      to touch and pain perception.
AB  - Every moment of every day, our skin and its embedded sensory neurons are
      bombarded with mechanical cues that we experience as pleasant or painful. Knowing
      the difference between innocuous and noxious mechanical stimuli is critical for
      survival and relies on the function of mechanoreceptor neurons that vary in their
      size, shape, and sensitivity. Their function is poorly understood at the
      molecular level. This review emphasizes the importance of integrating analysis at
      the molecular and cellular levels and focuses on the discovery of ion channel
      proteins coexpressed in the mechanoreceptors of worms, flies, and mice.

PMID- 22632720
TI  - High-resolution proteomics unravel architecture and molecular diversity of native
      AMPA receptor complexes.
AB  - AMPA-type glutamate receptors (AMPARs) are responsible for a variety of processes
      in the mammalian brain including fast excitatory neurotransmission, postsynaptic
      plasticity, or synapse development. Here, with comprehensive and quantitative
      proteomic analyses, we demonstrate that native AMPARs are macromolecular
      complexes with a large molecular diversity. This diversity results from
      coassembly of the known AMPAR subunits, pore-forming GluA and three types of
      auxiliary proteins, with 21 additional constituents, mostly secreted proteins or
      transmembrane proteins of different classes. Their integration at distinct
      abundance and stability establishes the heteromultimeric architecture of native
      AMPAR complexes: a defined core with a variable periphery resulting in an
      apparent molecular mass between 0.6 and 1 MDa. The additional constituents change
      the gating properties of AMPARs and provide links to the protein dynamics
      fundamental for the complex role of AMPARs in formation and operation of
      glutamatergic synapses.

PMID- 22632721
TI  - The age of olfactory bulb neurons in humans.
AB  - Continuous turnover of neurons in the olfactory bulb is implicated in several key
      aspects of olfaction. There is a dramatic decline postnatally in the number of
      migratory neuroblasts en route to the olfactory bulb in humans, and it has been
      unclear to what extent the small number of neuroblasts at later stages
      contributes new neurons to the olfactory bulb. We have assessed the age of
      olfactory bulb neurons in humans by measuring the levels of nuclear bomb test
      derived (14)C in genomic DNA. We report that (14)C concentrations correspond to
      the atmospheric levels at the time of birth of the individuals, establishing that
      there is very limited, if any, postnatal neurogenesis in the human olfactory
      bulb. This identifies a fundamental difference in the plasticity of the human
      brain compared to other mammals.

PMID- 22632722
TI  - TRPV1 in GABAergic interneurons mediates neuropathic mechanical allodynia and
      disinhibition of the nociceptive circuitry in the spinal cord.
AB  - Neuropathic pain and allodynia may arise from sensitization of central circuits.
      We report a mechanism of disinhibition-based central sensitization resulting from
      long-term depression (LTD) of GABAergic interneurons as a consequence of TRPV1
      activation in the spinal cord. Intrathecal administration of TRPV1 agonists led
      to mechanical allodynia that was not dependent on peripheral TRPV1 neurons. TRPV1
      was functionally expressed in GABAergic spinal interneurons and activation of
      spinal TRPV1 resulted in LTD of excitatory inputs and a reduction of inhibitory
      signaling to spinothalamic tract (STT) projection neurons. Mechanical
      hypersensitivity after peripheral nerve injury was attenuated in TRPV1(-/-) mice
      but not in mice lacking TRPV1-expressing peripheral neurons. Mechanical pain was
      reversed by a spinally applied TRPV1 antagonist while avoiding the hyperthermic
      side effect of systemic treatment. Our results demonstrate that spinal TRPV1
      plays a critical role as a synaptic regulator and suggest the utility of central
      nervous system-specific TRPV1 antagonists for treating neuropathic pain.

PMID- 22632723
TI  - Sensory experience restructures thalamocortical axons during adulthood.
AB  - The brain's capacity to rewire is thought to diminish with age. It is widely
      believed that development stabilizes the synapses from thalamus to cortex and
      that adult experience alters only synaptic connections between cortical neurons.
      Here we show that thalamocortical (TC) inputs themselves undergo massive
      plasticity in adults. We combined whole-cell recording from individual
      thalamocortical neurons in adult rats with a recently developed automatic tracing
      technique to reconstruct individual axonal trees. Whisker trimming substantially
      reduced thalamocortical axon length in barrel cortex but not the density of TC
      synapses along a fiber. Thus, sensory experience alters the total number of TC
      synapses. After trimming, sensory stimulation evoked more tightly time-locked
      responses among thalamorecipient layer 4 cortical neurons. These findings
      indicate that thalamocortical input itself remains plastic in adulthood, raising
      the possibility that the axons of other subcortical structures might also remain
      in flux throughout life.

PMID- 22632724
TI  - Encoding goals but not abstract magnitude in the primate prefrontal cortex.
AB  - Functional neuroimaging studies show that perceptual judgments about time and
      space activate similar prefrontal and parietal areas, and it is known that
      perceptions in these two cognitive domains interfere with each other. These
      findings have led to the theory that temporal and spatial perceptions, among
      other metrics, draw on a common representation of magnitude. Our results indicate
      that an alternative principle applies to the prefrontal cortex. Analysis at the
      single-cell level shows that separate, domain-specific populations of neurons
      encode relative magnitude in time and space. These neurons are intermixed with
      each other in the prefrontal cortex, along with a separate intermixed population
      that encodes the goal chosen on the basis of these perceptual decisions. As a
      result, domain-specific neural processing at the single-cell level seems to
      underlie domain generality as observed at the regional level, with a common
      representation of prospective goals rather than a common representation of
      magnitude.

PMID- 22632725
TI  - Forebrain GABAergic neuron precursors integrate into adult spinal cord and reduce
      injury-induced neuropathic pain.
AB  - Neuropathic pain is a chronic debilitating disease characterized by mechanical
      allodynia and spontaneous pain. Because symptoms are often unresponsive to
      conventional methods of pain treatment, new therapeutic approaches are essential.
      Here, we describe a strategy that not only ameliorates symptoms of neuropathic
      pain but is also potentially disease modifying. We show that transplantation of
      immature telencephalic GABAergic interneurons from the mouse medial ganglionic
      eminence (MGE) into the adult mouse spinal cord completely reverses the
      mechanical hypersensitivity produced by peripheral nerve injury. Underlying this
      improvement is a remarkable integration of the MGE transplants into the host
      spinal cord circuitry, in which the transplanted cells make functional
      connections with both primary afferent and spinal cord neurons. By contrast, MGE
      transplants were not effective against inflammatory pain. Our findings suggest
      that MGE-derived GABAergic interneurons overcome the spinal cord
      hyperexcitability that is a hallmark of nerve injury-induced neuropathic pain.

PMID- 22632726
TI  - Optic chiasm presentation of Semaphorin6D in the context of Plexin-A1 and Nr-CAM
      promotes retinal axon midline crossing.
AB  - At the optic chiasm, retinal ganglion cells (RGCs) project ipsi- or
      contralaterally to establish the circuitry for binocular vision. Ipsilateral
      guidance programs have been characterized, but contralateral guidance programs
      are not well understood. Here, we identify a tripartite molecular system for
      contralateral RGC projections: Semaphorin6D (Sema6D) and Nr-CAM are expressed on
      midline radial glia and Plexin-A1 on chiasm neurons, and Plexin-A1 and Nr-CAM are
      also expressed on contralateral RGCs. Sema6D is repulsive to contralateral RGCs,
      but Sema6D in combination with Nr-CAM and Plexin-A1 converts repulsion to growth
      promotion. Nr-CAM functions as a receptor for Sema6D. Sema6D, Plexin-A1, and Nr
      CAM are all required for efficient RGC decussation at the optic chiasm. These
      findings suggest a mechanism by which a complex of Sema6D, Nr-CAM, and Plexin-A1
      at the chiasm midline alters the sign of Sema6D and signals Nr-CAM/Plexin-A1
      receptors on RGCs to implement the contralateral RGC projection.

PMID- 22632728
TI  - Balance of activity between LN(v)s and glutamatergic dorsal clock neurons
      promotes robust circadian rhythms in Drosophila.
AB  - Circadian rhythms offer an excellent opportunity to dissect the neural circuits
      underlying innate behavior because the genes and neurons involved are relatively
      well understood. We first sought to understand how Drosophila clock neurons
      interact in the simple circuit that generates circadian rhythms in larval light
      avoidance. We used genetics to manipulate two groups of clock neurons, increasing
      or reducing excitability, stopping their molecular clocks, and blocking
      neurotransmitter release and reception. Our results revealed that lateral neurons
      (LN(v)s) promote and dorsal clock neurons (DN(1)s) inhibit light avoidance, these
      neurons probably signal at different times of day, and both signals are required
      for rhythmic behavior. We found that similar principles apply in the more complex
      adult circadian circuit that generates locomotor rhythms. Thus, the changing
      balance in activity between clock neurons with opposing behavioral effects
      generates robust circadian behavior and probably helps organisms transition
      between discrete behavioral states, such as sleep and wakefulness.

PMID- 22632727
TI  - Microglia sculpt postnatal neural circuits in an activity and complement
      dependent manner.
AB  - Microglia are the resident CNS immune cells and active surveyors of the
      extracellular environment. While past work has focused on the role of these cells
      during disease, recent imaging studies reveal dynamic interactions between
      microglia and synaptic elements in the healthy brain. Despite these intriguing
      observations, the precise function of microglia at remodeling synapses and the
      mechanisms that underlie microglia-synapse interactions remain elusive. In the
      current study, we demonstrate a role for microglia in activity-dependent synaptic
      pruning in the postnatal retinogeniculate system. We show that microglia engulf
      presynaptic inputs during peak retinogeniculate pruning and that engulfment is
      dependent upon neural activity and the microglia-specific phagocytic signaling
      pathway, complement receptor 3(CR3)/C3. Furthermore, disrupting microglia
      specific CR3/C3 signaling resulted in sustained deficits in synaptic
      connectivity. These results define a role for microglia during postnatal
      development and identify underlying mechanisms by which microglia engulf and
      remodel developing synapses.

PMID- 22632729
TI  - BAD-dependent regulation of fuel metabolism and K(ATP) channel activity confers
      resistance to epileptic seizures.
AB  - Neuronal excitation can be substantially modulated by alterations in metabolism,
      as evident from the anticonvulsant effect of diets that reduce glucose
      utilization and promote ketone body metabolism. We provide genetic evidence that
      BAD, a protein with dual functions in apoptosis and glucose metabolism, imparts
      reciprocal effects on metabolism of glucose and ketone bodies in brain cells.
      These effects involve phosphoregulation of BAD and are independent of its
      apoptotic function. BAD modifications that reduce glucose metabolism produce a
      marked increase in the activity of metabolically sensitive K(ATP) channels in
      neurons, as well as resistance to behavioral and electrographic seizures in vivo.
      Seizure resistance is reversed by genetic ablation of the K(ATP) channel,
      implicating the BAD-K(ATP) axis in metabolic control of neuronal excitation and
      seizure responses.

PMID- 22632730
TI  - Thalamocortical inputs show post-critical-period plasticity.
AB  - Experience-dependent plasticity in the adult brain has clinical potential for
      functional rehabilitation following central and peripheral nerve injuries. Here,
      plasticity induced by unilateral infraorbital (IO) nerve resection in 4-week-old
      rats was mapped using MRI and synaptic mechanisms were elucidated by slice
      electrophysiology. Functional MRI demonstrates a cortical potentiation compared
      to thalamus 2 weeks after IO nerve resection. Tracing thalamocortical (TC)
      projections with manganese-enhanced MRI revealed circuit changes in the spared
      layer 4 (L4) barrel cortex. Brain slice electrophysiology revealed TC input
      strengthening onto L4 stellate cells due to an increase in postsynaptic strength
      and the number of functional synapses. This work shows that the TC input is a
      site for robust plasticity after the end of the previously defined critical
      period for this input. Thus, TC inputs may represent a major site for adult
      plasticity in contrast to the consensus that adult plasticity mainly occurs at
      cortico-cortical connections.

PMID- 22632731
TI  - Conserved fMRI and LFP signals during new associative learning in the human and
      macaque monkey medial temporal lobe.
AB  - We measured local field potential (LFP) and blood-oxygen-level-dependent (BOLD)
      functional magnetic resonance imaging (fMRI) in the medial temporal lobes of
      monkeys and humans, respectively, as they performed the same conditional motor
      associative learning task. Parallel analyses were used to examine both data sets.
      Despite significantly faster learning in humans relative to monkeys, we found
      equivalent neural signals differentiating new versus highly familiar stimuli,
      first stimulus presentation, trial outcome, and learning strength in the
      entorhinal cortex and hippocampus of both species. Thus, the use of parallel
      behavioral tasks and analyses in monkeys and humans revealed conserved patterns
      of neural activity across the medial temporal lobe during an associative learning
      task.

PMID- 22632732
TI  - A cortical core for dynamic integration of functional networks in the resting
      human brain.
AB  - We used magneto-encephalography to study the temporal dynamics of band-limited
      power correlation at rest within and across six brain networks previously defined
      by prior functional magnetic resonance imaging (fMRI) studies. Epochs of
      transiently high within-network band limited power (BLP) correlation were
      identified and correlation of BLP time-series across networks was assessed in
      these epochs. These analyses demonstrate that functional networks are not
      equivalent with respect to cross-network interactions. The default-mode network
      and the posterior cingulate cortex, in particular, exhibit the highest degree of
      transient BLP correlation with other networks especially in the 14-25 Hz (beta
      band) frequency range. Our results indicate that the previously demonstrated
      neuroanatomical centrality of the PCC and DMN has a physiological counterpart in
      the temporal dynamics of network interaction at behaviorally relevant timescales.
      This interaction involved subsets of nodes from other networks during periods in
      which their internal correlation was low.

PMID- 22632734
TI  - Narrowband ultraviolet B three times per week is more effective in treating
      vitamin D deficiency than 1600 IU oral vitamin D3 per day: a randomized clinical
      trial.
AB  - BACKGROUND: It is known that narrowband ultraviolet B (NB-UVB) radiation and oral
      vitamin D(3) supplementation can both improve serum levels of vitamin D,
      expressed as 25-hydroxyvitamin D(3) [25(OH)D(3) ]. However, surprisingly few
      studies have compared the effects of the two interventions in treating vitamin D
      deficiency. OBJECTIVES: To compare the effect of NB-UVB exposure with oral
      vitamin D(3) supplementation on vitamin D levels in patients with vitamin D
      deficiency. METHODS: Seventy-three participants with vitamin D deficiency
      [25(OH)D(3) <= 25 nmol L(-1) ] were consecutively enrolled from February 2010 to
      May 2011, avoiding the summer period (June to September). The participants were
      randomized into two groups, one receiving full body NB-UVB exposure three times
      per week, the other receiving 1600 IU (40 MUg) oral vitamin D(3) per day together
      with 1,000 mg calcium. Thirty-two participants completed the 6-week study period,
      16 in each group. In both groups blood samples were obtained at baseline and
      after 3 and 6 weeks. RESULTS: We found a significantly greater increase in
      25(OH)D(3) levels (mean) in the NB-UVB treated group (from 19.2 to 75 nmol L(-1)
      ) compared with the oral vitamin D(3) treated group (from 23.3 to 60.6 nmol L(-1)
      ) after 6 weeks of treatment (P = 0.02), accompanied by a significant decrease in
      parathyroid hormone for the whole group (from 5.3 to 4.2 pmol L(-1) , P = 0.028).
      CONCLUSIONS: Full body NB-UVB three times per week is more effective in treating
      vitamin D deficiency than prescription of a daily oral intake of 1600 IU (40 MUg)
      vitamin D(3) .

PMID- 22632735
TI  - Gulf War illnesses are autoimmune illnesses caused by reactive oxygen species
      which were caused by nerve agent prophylaxis.
AB  - Gulf War illnesses (GWI share many of the features of chronic fatigue syndrome
      (CFS) and both CFS and GWI may be the result of chronic immune system processes.
      The main suspected cause for GWI, the drug pyridostigmine bromide (PB), has been
      shown to cause neuronal damage from reactive oxygen species (ROS). ROS have been
      associated with IgM mediated autoimmune responses against ROS induced neoepitopes
      in depressed patients and this may also apply to CFS. It therefore follows that
      the drug used in the Gulf War caused ROS, the ROS modified native molecules, and
      that this trigged the autoimmune condition we refer to as Gulf War illnesses.
      Similar mechanisms may apply to other autoimmune illnesses.

PMID- 22632736
TI  - Patient comprehension and attitudes toward maintenance chemotherapy for lung
      cancer.
AB  - OBJECTIVE: Maintenance chemotherapy is a recently approved approach to the
      treatment of advanced non-small cell lung cancer (NSCLC). We sought to gain
      insight into patients' perceptions of maintenance chemotherapy using qualitative
      methods. METHODS: We conducted thematic content analysis of focus groups at a
      freestanding cancer center and at an associated safety-net county hospital.
      Patients with advanced NSCLC who had started but not yet completed first-line
      platinum doublet chemotherapy were provided visual and written explanations of
      maintenance chemotherapy before being guided in group discussion. RESULTS: Key
      themes to emerge for consideration of maintenance chemotherapy included: (1)
      survival benefits, disease control, and "buying time"; (2) the importance of
      "doing something"; (3) quality of life concerns; (4) the role of provider
      opinion/preference; and (5) the importance of logistics. CONCLUSIONS: Patients
      undergoing first-line chemotherapy for advanced NSCLC were able to understand the
      concept of maintenance chemotherapy, distinguish it from traditional treatment
      paradigms, identify pros and cons of this approach, and convey reasons for
      considering it. PRACTICE IMPLICATIONS: Advances in oncology care that alter
      therapy modalities and delivery may significantly impact patient perceptions and
      treatment experiences. Clinical team members may wish to elicit treatment
      preferences of first-line patients through clinical discussion that anticipate
      these considerations.

PMID- 22632737
TI  - The validity of education and guidance for clinical communication in cancer care:
      evidence-based practice will depend on practice-based evidence.
AB  - OBJECTIVE: The validity of clinical communication skills education and guidance
      for cancer care is sometimes portrayed as self-evident. This view needs re
      examination in light of critiques of the concept of communication skills.
      METHODS: We critically examine principles that steer communication teaching and
      guidance in cancer care and draw on research that can inform the next generation
      of development in this field. RESULTS: Unlike other areas of clinical skills,
      communication is highly contested. Any instance of communication is open to
      multiple interpretations; expert principles of communication are imprecise and
      often contradictory. The concept of communication skills will constrain
      development, because of its implication that universal, expert-defined components
      of communication are the building blocks of clinical relationships. Research on
      communication in practice indicates insights that could enrich future education
      and guidance. CONCLUSIONS: Communication experts have more to learn from
      practitioners and patients than is commonly appreciated. Inductive, qualitative
      research should incorporate patient and practitioner perspectives as well as
      observations of communication. PRACTICE IMPLICATIONS: Solutions to communication
      dilemmas might be found in detailed study of communication in practice, rather
      than in current expert principles. Incorporating such evidence will help to
      ensure the continued authority of communication curricula and guidance as
      evidence-based and patient-centred.

PMID- 22632738
TI  - The high resilience of the bacterioplankton community in the face of a
      catastrophic disturbance by a heavy  Microcystis bloom.
AB  - The accumulation and breakdown of cyanobacterial blooms often causes catastrophic
      changes in the aquatic fauna of lakes. Recovery from these changes is always
      prolonged. However, little is known about the resilience and recovery of the
      bacterioplankton community composition (BCC) after this type of disturbance. In
      this study, we examined the resistance and resilience of the BCC following a
      Microcystis bloom disturbance with in situ mesocosm experiments with varying
      levels of Microcystis biomass ranging from 75 to 13 012 MUg L(-1) , as measured
      by the chlorophyll-a concentration, over 13 days. The BCC was assessed with
      denaturing gradient gel electrophoresis of 16S rRNA genes, followed by cloning
      and sequencing of the selected samples. We observed a strong shift of the BCC
      from the control on the first day of the bloom disturbance. The most dramatic
      change in the BCC occurred in the mesocosm with the highest Microcystis biomass,
      in which the dissolved oxygen varied strongly. However, we observed a rapid
      recovery of the BCC from day 7, when most of the investigated environmental
      factors had also recovered. On day 12, the BCC in the different mesocosms
      resembled the control at day 0 to a greater extent than during the accumulation
      and breakdown of the Microcystis bloom. Our study indicated that although the
      resistance of the BCC is low, the resilience is high, even following a
      catastrophic disturbance by a Microcystis bloom in a freshwater lake.

PMID- 22632739
TI  - Using mobile fruit vendors to increase access to fresh fruit and vegetables for
      schoolchildren.
AB  - This study explored the extent to which schoolchildren purchased precut and
      bagged fruits and vegetables from a mobile fruit vendor (frutero). During 14 days
      in fall 2008, a frutero sold fruits and vegetables at the entrance of an
      elementary school; 59% of the frutero's 233 consumers of 248 items were
      elementary-school students. With each successive day, an average of 1 additional
      bag of fruits and vegetables was sold by the frutero and 1.5 fewer nonnutritious
      foods by a competing vendor. Policies encouraging the sale of nutritious foods
      from mobile food vendors may increase access for schoolchildren.

PMID- 22632740
TI  - Dissemination of an evidence-based program to reduce fear of falling, South
      Carolina, 2006-2009.
AB  - INTRODUCTION: Falls among older adults are a serious public health issue, and
      fear of falling can limit mobility, which in turn increases fall risk. A Matter
      of Balance/Volunteer Lay Leader Model is an evidence-based program designed to
      address fear of falling. The objective of this study was to describe
      implementation, dissemination, and outcomes of this program in 3 regions of South
      Carolina with a predominantly African American and largely underserved
      population. METHODS: We developed partnerships throughout the state, organized
      master and lay leader trainings, and documented numbers of lay leaders, programs
      offered, demographic characteristics of participants, program fidelity, and
      attendance. Outcome measures were self-reported confidence to prevent and manage
      falls and a quantitative measure of functional mobility. Both measures were
      assessed at baseline and after program completion. RESULTS: Older adults (N =
      235) attended 18 classes at 16 sites. Barriers to implementation were program
      teams' limited familiarity with the concept of evidence-based programs and the
      importance of adhering to program content. Facilitators were state-level
      leadership and a history of state, regional, and local groups collaborating
      successfully on other projects. Outcomes indicated greater confidence in managing
      falls and carrying out activities of daily living. Mobility improved
      significantly, suggesting a reduced risk for falls. CONCLUSION: Evidence-based
      programs such as A Matter of Balance/Volunteer Lay Leader Model can be
      successfully disseminated in underserved areas. Outcomes indicate that
      participation in fall prevention programs can benefit groups of predominantly
      African American older adults.

PMID- 22632741
TI  - Development and validation of a tool for assessing glucose impairment in
      adolescents.
AB  - INTRODUCTION: Childhood obesity is associated with an increased risk for type 2
      diabetes. Early identification of adolescents at risk for impaired fasting
      glucose may lead to earlier and more comprehensive evaluation and intervention.
      Because widespread glucose testing of adolescents is not recommended, community
      based tools are needed to identify those who could benefit from further testing.
      One such tool, developed for adults, was the Tool for Assessing Glucose
      ImpairmenT (TAG-IT). Our objective was to validate whether a similar tool could
      be useful for community-based screening of glucose impairment risk among
      adolescents. METHODS: Our study sample consisted of 3,050 adolescents aged 12 to
      18 years who had participated in the 1999-2008 National Health and Nutrition
      Examination Survey (NHANES). Half of participants were female and 40% were
      nonwhite. NHANES measured fasting glucose and height, weight, and resting heart
      rate. We used Pearson correlations and regression analysis to determine key
      variables for predicting glucose impairment. From these measurements, we created
      a composite TAG-IT score for adolescents called TAG-IT-A. We then applied the TAG
      IT-A model to 1988-1994 NHANES data, using linear regression analysis and
      receiver operating characteristic analysis to determine how well the TAG-IT-A
      score predicted a fasting glucose at or above 100 mg/dL. RESULTS: We determined
      that age, sex, body mass index, and resting heart rate were important predictors
      of impaired fasting glucose and that TAG-IT-A was a better predictor of impaired
      fasting glucose than body mass index alone (area under the curve, 0.61, P < .001
      vs 0.55, P = .10, respectively). A TAG-IT-A score of 3 or higher correctly
      identified 50% of adolescents with impaired fasting glucose, while a score of 5
      or higher correctly identified 76%. CONCLUSION: The TAG-IT-A score is a simple
      screening tool that clinicians and public health professionals could use to
      easily identify adolescents who may have impaired fasting glucose and need a more
      comprehensive evaluation.

PMID- 22632742
TI  - Independent association of waist circumference with hypertension and diabetes in
      African American women, South Carolina, 2007-2009.
AB  - INTRODUCTION: Obesity is associated with hypertension and diabetes, which are
      independent risk factors for cardiovascular disease (CVD); 53% of African
      American women are obese. Of the approximately 44% of African American women who
      are hypertensive, more than 87% are overweight or obese. Additionally, more than
      twice as many African American women (13.1%) as white women (6.1%) have been
      diagnosed with type 2 diabetes. Obesity is usually measured using body mass index
      (BMI). However, abdominal adiposity may be more predictive of CVD risk than BMI.
      This study investigates the independent association of waist circumference with
      hypertension and diabetes in African American women. METHODS: As part of the
      Faith, Activity, and Nutrition (FAN) program, we recruited 843 African American
      women (mean age 53.8 y [SD, 14.1 y]) from African Methodist Episcopal churches.
      If a participant reported she had hypertension or had measured systolic blood
      pressure at or higher than 140 mm Hg or measured diastolic blood pressure at or
      higher than 90 mm Hg, she was classified as having hypertension. To assess
      increased health risks associated with waist circumference, we used the World
      Health Organization's standards to categorize waist circumference as normal risk
      (waist circumference <80 cm), increased risk (waist circumference 80-88 cm), or
      substantially increased risk (waist circumference >88 cm). We used logistic
      regression models to test predictors of hypertension and diabetes. RESULTS: Of
      843 study participants, 205 had diabetes and 545 were hypertensive. Women with a
      waist circumference of 88 cm or more were at increased risk for hypertension
      (odds ratio [OR] = 7.17, P < .002) and diabetes (OR = 6.99, P < .001).
      Associations remained after controlling for all variables (hypertension OR =
      5.53, P < .001; diabetes, OR = 5.38, P < .001). CONCLUSION: After controlling for
      all variables, waist circumference was independently associated with a 5-fold
      risk in hypertension and diabetes in African American women.

PMID- 22632744
TI  - The effect of intravenous magnesium therapy on the duration of intrathecal
      fentanyl labor analgesia.
AB  - BACKGROUND: Magnesium has been reported to augment the analgesic effects of
      opioids when co-administered into the cerebrospinal fluid. The purpose of this
      study was to determine the influence of intravenous magnesium therapy
      administered for preeclampsia on the duration of intrathecal fentanyl analgesia
      for labor. METHODS: Thirty-four nulliparous parturients having labor induced for
      preeclampsia and receiving intravenous magnesium therapy were recruited. Thirty
      four nulliparous patients having labor induced for elective or medical reasons
      were recruited as controls. At request for analgesia, baseline serum magnesium
      levels were obtained and combined spinal-epidural analgesia was initiated with
      intrathecal fentanyl 25MUg. Before injection of fentanyl, a sample of
      cerebrospinal fluid was obtained for magnesium assay. An epidural catheter was
      sited but no additional medications were administered until the second request
      for analgesia. The primary outcome was duration of intrathecal fentanyl
      analgesia. RESULTS: There was no difference in the median duration of analgesia
      between the magnesium [79min (95% CI 76 to 82)] and control groups [69min (95% CI
      56 to 82)] (difference between medians: 10min (95% CI -4 to 21min; P=0.16). There
      was neither a relationship between the serum and cerebrospinal fluid magnesium
      concentrations nor the cerebrospinal magnesium concentration and duration of
      intrathecal fentanyl analgesia. CONCLUSIONS: Intravenous magnesium therapy at
      doses typically used for seizure prophylaxis in preeclampsia did not influence
      the duration of intrathecal fentanyl labor analgesia. However, this study may
      have been underpowered to detect a difference and future study is warranted.

PMID- 22632745
TI  - Urgent cesarean delivery and prolonged ventilatory support in a parturient with
      Fontan circulation and undiagnosed pseudocholinesterase deficiency.

PMID- 22632746
TI  - Special issue: Network approaches in complex environments.

PMID- 22632747
TI  - Special issue: Progress in shoulder biomechanics.

PMID- 22632748
TI  - Molecular link mechanisms between inflammation and cancer.
AB  - Inflammation is part of the body's response to internal and external
      environmental stimuli that normally eliminate the aggressor agent and restore the
      tissue physiology. However, when it becomes chronic, it can cause several
      pathologies such as cardiovascular, diabetes, rheumatoid arthritis, Alzheimer's
      autoimmune diseases and cancer. Currently, epidemiological data indicate that
      over 25% of all cancers are related to chronic infections and other types of
      unresolved inflammation. Further evidence of this relationship is the fact that
      prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) has been
      associated with reduced risk to developing many types of cancers. Some randomized
      trials have shown that NSAIDs have protective action against colon adenomas,
      breast, prostate, and lung cancers. The inflammation present on tumor
      microenvironment is characterized by leukocyte infiltration, ranging in size,
      distribution and composition, as: tumor-associated macrophages (TAM), mast cells,
      dendritic cells, natural killer (NK) cells, neutrophils, eosinophils and
      lymphocytes. These cells produce a variety of cytotoxic mediators such as
      reactive oxygen and nitrogen species (ROS and RNS respectively), serine and
      cysteine proteases, membrane perforating agents, matrix metalloproteinase (MMP),
      tumor necrosis factor alpha (TNFalpha), interleukins (IL-1, IL-6, IL-8),
      interferons (IFNs) and enzymes, as cyclooxygenase-2 (COX-2), lipooxygenase-5 (LOX
      5) and phospholipase A2 (PLA2), which activate or are activated by transcription
      factors as nuclear factor kappaB (NF-kappaB) and signal transducers and
      activators of transcription-3 (STAT3). Initially this paper will briefly review
      the main mediators present on tumor microenvironment, addressing the cytokines,
      chemokines, transcription factors, eicosanoid, and kinins and later, will present
      an overview of the role of inflammation in the different steps of carcinogenesis.

PMID- 22632749
TI  - Tobacco, inflammation, and respiratory tract cancer.
AB  - Cigarette smoking is the most recognized risk factor for many inflammatory
      diseases such as cardiovascular diseases, chronic obstructive pulmonary disease
      and for a number of malignances such as lung cancer. Lung cancer is currently
      considered the leading cause of cancer-related deaths because its aggressive
      nature and the lack of effective therapeutic options. Recent advances in
      molecular biology and immunology have improved the knowledge on different
      mechanisms implicated in lung cell malignant transformation, progression and
      metastasis, thus presenting an exciting new era for lung anticancer therapies.
      The way by which cigarette smoke may induce lung malignancy includes a large
      number of different mechanisms and substances, most of them currently unknown.
      Thus, identified carcinogenic compounds of cigarette smoke may induce themselves
      a direct cytotoxicity and mutagenic action on lung epithelial cells by means of
      generation of somatic mutations, epigenetic events, epithelial cell to
      mesenchymal cell transformations, as well as by chronic cell damage. However, the
      fact that there is a relative high prevalence of ex-smoker who may develop lung
      cancer after years of smoking cessation suggest that other causes are also
      implicated. Thus cigarette smoke-induced chronic lung inflammatory
      microenvironment, oxidative stress and cell structural alterations such as the
      increase of cell proliferation, angiogenesis and apoptosis arrest are
      irreversible processes that have a high influence in lung tumor growth. In this
      review we focused in current knowledge on the mechanisms implicated in cigarette
      smoke-induced lung chronic inflammatory processes leading to lung carcinogenesis,
      as well as in current therapies based on novel molecular advances.

PMID- 22632750
TI  - Reactive oxygen species, inflammation, and lung diseases.
AB  - Reactive oxygen species (ROS) are well recognized for playing a dual role as both
      deleterious and beneficial species. ROS are products of normal cellular
      metabolism and under physiological conditions, participate in maintenance of
      cellular 'redox homeostasis. Overproduction of ROS, results in oxidative stress.
      Oxidative stress is a deleterious process that leads to lung damage and
      consequently to various disease states. The lung is a highly specialized organ
      that facilitates uptake of oxygen and release of carbon dioxide. Persistent
      inhalation of the invading pathogens or toxic agents may result in overwhelming
      production of ROS. Oxidants initiate a number of pathologic processes, including
      inflammation of the airways, which may contribute to the pathogenesis and/or
      exacerbation of airways disease. During inflammation, enhanced ROS production may
      induce recurring DNA damage, inhibition of apoptosis, and activation of
      protooncogenes by initiating signal transduction pathways. Therefore, it is
      conceivable that chronic inflammation-induced production of ROS in the lung may
      predispose individuals to lung diseases. In this review, we discuss mechanisms of
      oxidant stress in the lung, the role of oxidants in lung disease pathogenesis and
      exacerbation.

PMID- 22632751
TI  - Pharmacological control of autophagy: therapeutic perspectives in inflammatory
      bowel disease and colorectal cancer.
AB  - Autophagy, an intracellular process involved in removing and recycling cellular
      components, plays a major role in growth, development, and responses to stress
      and pathogens. Autophagy is compromised in many human diseases, including
      inflammatory bowel disease (IBD) and colorectal cancer (CRC). Autophagy
      malfunction is associated to an alteration of both innate and adaptative immune
      responses, defects in bacterial clearance, and malfunction of goblet and Paneth
      cells; all these perturbations are related to IBD and CRC pathogenesis.
      Preclinical data show that both inhibition and induction of autophagy have
      significant potential to be translated into the clinic. Inhibitors of TORC1
      (rapamycin and rapalogs) have proven to be effective in IBD and in many models
      for CRCs; however, their clinical use has produced only modest success. Second
      generations of mTOR inhibitors, which target its kinase domain, have been more
      effective. Optimal antitumor efficacy is achieved by combination of agents with
      different molecular targets, such as proteasome or histone deacetylase inhibitors
      combined with autophagy inhibitors (hydroxychloroquine) or activators
      (everolimus). Clinical trials in course are assaying the effect of these
      compounds in combination with standard treatments of CRC. This review summarizes
      current knowledge about the autophagic machinery and its regulation, then it
      explores the relevance and impact of the malfunction of autophagy on the
      pathogenesis of IBD and CRC, and, finally, it discusses the therapeutic potential
      of molecules that regulate autophagy and their use for the treatment of these two
      diseases.

PMID- 22632752
TI  - Non-steroidal anti-inflammatory drugs and melanoma.
AB  - Inflammation is an important contributor to the development and progression of
      all human cancers. Inflammatory lipid metabolites, prostaglandins, formed from
      arachidonic acid by prostaglandin H synthases commonly called cyclooxygenases
      (COXs), bind to specific receptors that activate signaling pathways driving to
      the development and progression of tumors. Inhibitors of prostaglandin formation,
      COX inhibitors, including non-steroidal anti-inflammatory drugs (NSAIDs), are
      well documented agents that inhibit tumor growth and prevent tumor development
      specially due to long-term use. NSAIDs also alter gene expression independently
      of COX inhibition which also appear to contribute to the anti-tumorigenic
      activity of these drugs. In a dermatologic point of view, most investigations are
      oriented to improve the current knowledge related to the pathogenesis of
      malignant melanoma, a prevalent skin cancer characterized by a rapid progression
      with frequent metastases and a poor response to the different available
      treatments. In the present issue we review the role of inflammation in cutaneous
      malignant melanoma and its impact on cancer pathogenesis. This topic represents
      an exciting new area of research, and could potentially result in new targets for
      melanoma therapy in the future.

PMID- 22632753
TI  - TGF-beta1 signalling, connecting aberrant inflammation and colorectal
      tumorigenesis.
AB  - TGF-beta1 is an anti-inflammatory cytokine recognised as a key regulator of
      immunological homeostasis and inflammatory responses. Furthermore, TGF-beta1 is
      important for the regulation of cell growth, differentiation and apoptosis in a
      wide range of tissues including the intestinal epithelium. Reduced TGF-beta1
      activity is thought to be responsible for the development of autoimmune disorders
      in several pathological conditions, including inflammatory bowel disease [IBD].
      Although the cause of IBD is not yet known, research has shown that a number of
      factors may be involved including environment, diet and genetics, as well as
      cytokine exposure. Importantly, IBD is also associated with an increased lifetime
      risk of developing colorectal cancer, which remains the fourth most common cancer
      worldwide, representing a significant therapeutic challenge. As functionally
      implicated in both maintenance of the immune response and tissue homeostasis in
      the colon, TGF-beta1 signalling potentially sits at the crossroads between
      aberrant inflammation and colorectal tumorigenesis. Hence, the purpose of this
      paper is to review the evidence for cross talk between TGF-beta1 signalling and
      pathways important for colorectal tissue homeostasis, with the emphasis on
      understanding how deregulation of TGF-beta1 signalling contributes not only to
      aberrant inflammatory disease but also to colorectal tumour progression.

PMID- 22632754
TI  - Non-aspirin non-steroidal anti-inflammatory drugs for the primary chemoprevention
      of non-gastrointestinal cancer: summary of evidence.
AB  - BACKGROUND: There is evidence that aspirin is effective for the chemoprevention
      of colorectal cancer. Due to their similar pharmacodynamics, the use of other non
      steroidal anti-inflammatory drugs (NSAIDs) has been suggested for other cancer
      sites. Although this possibility has been discussed in the literature,
      uncertainty remains about the actual effects of NSAIDs other than aspirin in
      nongastrointestinal cancer. OBJECTIVE: To summarize the best available evidence
      of the primary chemopreventive effects of non-aspirin NSAIDs for
      nongastrointestinal cancer. METHODS: Our inclusion criteria were narrative or
      systematic reviews, clinical guidelines and, if they had not been previously
      included, primary controlled studies that evaluated the effectiveness of non
      aspirin NSAIDs in preventing non-gastrointestinal cancer in healthy individuals.
      Studies were retrieved from the following databases: Guidelines.gov, BMJ Clinical
      Evidence, TRIP database, UpToDate, MEDLINE, CANCERLIT, Embase, CINAHL, ISI Web of
      Science and Scopus. Two independent reviewers selected eligible studies. Data
      were extracted by one reviewer and crosschecked by two others. RESULTS: We found
      9,984 non-duplicated articles and included 56 eligible studies. Most of these
      studies were observational. The studies reported conflicting results or no
      statistically significant associations between the use of non-aspirin NSAIDs and
      risk of lung, ovary, bladder, prostate, skin, and head and neck cancers. In
      contrast, an increased risk of renal cell carcinoma and a reduced risk of breast
      cancer were found to be statistically significant. The included studies had
      methodological limitations, which reduces our confidence in their results.
      CONCLUSIONS: We did not find sufficient evidence to support the use of the non
      aspirin NSAIDs for the primary chemoprevention of a wide variety of non
      gastrointestinal cancers. This scenario suggests caution when considering the
      routine use of non-aspirin NSAIDs. Additional well-conducted controlled studies
      may provide more conclusive evidence on this issue, but there are concerns about
      the risks of such exposure.

PMID- 22632755
TI  - Chemoprevention with phytonutrients and microalgae products in chronic
      inflammation and colon cancer.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disorder caused by
      deregulated immune responses in a genetically predisposed individual. This is a
      complex process mediated by cytokines, chemokines, adhesion molecules, cytoplasm
      nuclear receptors, among others. Recent data support a participation of the
      endoplasmic reticulum (ER) stress and mitochondrial dysfunctions in IBD.
      Moreover, now it is evident that chronic degenerative pathologies, including IBD,
      share comparable disease mechanisms at the cellular level with alteration of the
      autophagy mechanisms. Mounting evidence suggests that the risk of developing
      colorectal cancer (CRC) is dramatically increased in patients with chronic
      inflammatory disease. Chronic inflammation in IBD exposes these patients to a
      number of signals known to have tumorigenic effects including nuclear factor
      kappa B (NF-kappaB) activation, proinflammatory cytokines and prostaglandins
      release and reactive oxygen species (ROS) production. Chemoprevention consists in
      the use of drugs, vitamins, or nutritional supplements to reduce the risk of
      developing, or having a recurrence of cancer. Numerous in vitro and animal
      studies have established the potential colon cancer chemopreventive properties of
      phytochemicals derived from both plants (curcumin, resveratrol, epigallocatechin
      gallate, quercetin or genistein) and substances from marine environment,
      including microalgae species and their products. This review summarizes the
      mechanisms by which these naturally occurring compounds may mediate
      chemopreventive effects on cancer. These actions include induction of cell cycle
      arrest and apoptosis, inhibition of cell proliferation, stimulation of
      antimetastatic and antiangiogenic responses and increased antioxidant and anti
      inflammatory activity.

PMID- 22632756
TI  - Molecules of natural origin, semi-synthesis and synthesis with anti-inflammatory
      and anticancer utilities.
AB  - The development of new drugs that can be valuable for the evolution of diseases'
      treatment is a goal for different areas of research, namely natural products
      chemistry, molecular biology and biochemistry, pharmacology, medicinal chemistry,
      synthetic organic chemistry and analytical chemistry. Nature is the main source
      of compounds for pharmaceutical purposes, either by providing the natural organic
      chemical compounds of interest or as a source of inspiration for the design of
      new drugs. The known anti-inflammatory and anticancer agents belong to a great
      diversity of structural skeletons since inflammatory and cancer processes involve
      many different biological targets. Their origins extend to plants, fungi,
      bacteria, and marine organisms, besides those produced by semi-synthesis and
      total synthesis. The tasks of the organic chemist are the screening, the
      structure assignment, and the semi and total syntheses of active molecules.
      Herein the screening and assignment of new active structures is addressed,
      together with other aspects, namely the improvements, both in availability and in
      effectiveness of action that can be achieved from new derivatives by synthetic or
      semi-synthetic strategies. Some aspects of drug delivery of anti-inflammatory and
      anticancer agents are considered. The bibliography presented is far from being
      exhaustive due to the prodigious number of published works. Instead, the most
      significant contributions in the scope of this review are described. The active
      compounds are organised by their biosynthetic origins as terpenoids; macrolides,
      polyketides and ansamycins; phenolics; alkaloids; peptides; glycoconjugates;
      other compounds, and food compounds.

PMID- 22632757
TI  - Is prospective memory enhanced by cue-action semantic relatedness and enactment
      at encoding?
AB  - Benefits and costs on prospective memory performance, of enactment at encoding
      and a semantic association between a cue-action word pair, were investigated in
      two experiments. Findings revealed superior performance for both younger and
      older adults following enactment, in contrast to verbal encoding, and when cue
      action semantic relatedness was high. Although younger adults outperformed older
      adults, age did not moderate benefits of cue-action relatedness or enactment.
      Findings from a second experiment revealed that the inclusion of an instruction
      to perform a prospective memory task led to increments in response latency to
      items from the ongoing activity in which that task was embedded, relative to
      latencies when the ongoing task only was performed. However, this task
      interference 'cost' did not differ as a function of either cue-action relatedness
      or enactment. We argue that the high number of cue-action pairs employed here
      influenced meta-cognitive consciousness, hence determining attention allocation,
      in all experimental conditions.

PMID- 22632759
TI  - Microbial proteomics: the quiet revolution.

PMID- 22632758
TI  - Knowing a lot for one's age: Vocabulary skill and not age is associated with
      anticipatory incremental sentence interpretation in children and adults.
AB  - Adults can incrementally combine information from speech with astonishing speed
      to anticipate future words. Concurrently, a growing body of work suggests that
      vocabulary ability is crucially related to lexical processing skills in children.
      However, little is known about this relationship with predictive sentence
      processing in children or adults. We explore this question by comparing the
      degree to which an upcoming sentential theme is anticipated by combining
      information from a prior agent and action. 48 children, aged of 3 to 10, and 48
      college-aged adults' eye-movements were recorded as they heard a sentence (e.g.,
      The pirate hides the treasure) in which the object referred to one of four images
      that included an agent-related, action-related and unrelated distractor image.
      Pictures were rotated so that, across all versions of the study, each picture
      appeared in all conditions, yielding a completely balanced within-subjects
      design. Adults and children quickly made use of combinatory information available
      at the action to generate anticipatory looks to the target object. Speed of
      anticipatory fixations did not vary with age. When controlling for age,
      individuals with higher vocabularies were faster to look to the target than those
      with lower vocabulary scores. Together, these results support and extend current
      views of incremental processing in which adults and children make use of
      linguistic information to continuously update their mental representation of
      ongoing language.

PMID- 22632760
TI  - Microbial metaproteomics: identifying the repertoire of proteins that
      microorganisms use to compete and cooperate in complex environmental communities.
AB  - The availability of genome information for microbial consortia, including
      unculturable species, from environmental samples has enabled systems-biology
      interrogation by providing a means to access genomic, transcriptomic, and
      proteomic information. This provides a unique opportunity to characterize the
      molecular activities and interactions of these microbial systems at a
      comprehensive level never before possible. Such information not only provides
      details about the organizational, functional, and metabolic activities of such
      systems, but also the untapped reserve of molecular activities that might be
      invoked and exploited under certain environmental conditions. Since bacteria
      naturally exist in complex ecosystems, it is imperative to develop and utilize
      analytical approaches that can provide molecular level details on systems
      consisting of mixed microbial membership. This is the realm of metaproteomics-the
      characterization of the complement of proteins expressed by a microbial community
      in an environmental sample.

PMID- 22632761
TI  - Identification of drugs including a dopamine receptor antagonist that selectively
      target cancer stem cells.
AB  - Selective targeting of cancer stem cells (CSCs) offers promise for a new
      generation of therapeutics. However, assays for both human CSCs and normal stem
      cells that are amenable to robust biological screens are limited. Using a
      discovery platform that reveals differences between neoplastic and normal human
      pluripotent stem cells (hPSC), we identify small molecules from libraries of
      known compounds that induce differentiation to overcome neoplastic self-renewal.
      Surprisingly, thioridazine, an antipsychotic drug, selectively targets the
      neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic
      disease initiation while having no effect on normal blood SCs. The drug
      antagonizes dopamine receptors that are expressed on CSCs and on breast cancer
      cells as well. These results suggest that dopamine receptors may serve as a
      biomarker for diverse malignancies, demonstrate the utility of using neoplastic
      hPSCs for identifying CSC-targeting drugs, and provide support for the use of
      differentiation as a therapeutic strategy.

PMID- 22632762
TI  - Clinical effectiveness of transversus abdominis plane (TAP) block in abdominal
      surgery: a systematic review and meta-analysis.
AB  - AIM: Reduced opioid use in the immediate postoperative period is associated with
      decreased complications. This study aimed to determine the effect of transversus
      abdominis plane (TAP) block on morphine requirements 24 h after abdominal
      surgery. Secondary outcomes included the effect of TAP block on morphine use 48 h
      after surgery, incidence of postoperative nausea and vomiting (PONV) and impact
      on reported pain scores (visual analogue scale). METHOD: A systematic review of
      the literature was conducted for randomised controlled trials (RCTs) evaluating
      the effects of TAP block in adults undergoing abdominal surgery. For continuous
      data, weighted mean differences (WMD) were formulated; for dichotomous data, odds
      ratios (OR) were calculated. Results were produced with a random effects model
      with 95% confidence intervals (CI). RESULTS: Nine studies, including published
      and unpublished data, containing a total of 413 patients were included. Of these
      205 received a TAP block and 208 a placebo. Cumulative morphine utilization was
      statistically significantly reduced at 24 h. [WMD=23.71mg (38.66-8.76); P=0.002]
      and 48h [WMD=38.08mg (18.97-57.19); P<0.0001] in patients who received a TAP
      block and the incidence of PONV was significantly reduced [OR=0.41(0.22-0.74);
      P=0.003]. There was a nonsignificant reduction in the visual analogue scales of
      postoperative pain [WMD=0.73cm (1.84-0.38), P=0.2]. There were no reported
      adverse events following TAP block. CONCLUSION: Transversus abdominis plane block
      is safe, reduces postoperative morphine requirements, nausea and vomiting and
      possibly the severity of pain after abdominal surgery. It should be considered as
      part of a multimodal approach to anaesthesia and enhanced recovery in patients
      undergoing abdominal surgery.

PMID- 22632763
TI  - Empathic curiosity: resolving goal conflicts that generate emotional distress.
AB  - The quality of the therapeutic alliance between therapist and client is
      consistently identified as a key component of cognitive behavioural
      interventions. However, relatively little is known about the causal mechanisms
      that generate the effects that are ascribed to the therapeutic alliance. This
      paper outlines how one such causal mechanism, empathic curiosity, may operate.
      The explanation is rooted in control theory, a theory that explains the link
      between our experiences and our goal-directed behaviour. Empathic curiosity is
      underpinned by the core skills of empathic listening and maintaining a curious
      attitude. From a control theory perspective, the value of this type of listening
      may be reinforced when speak to people about their salient concerns, as they
      perceive them in the current flow of their conscious thoughts. This can be
      facilitated by linking curious questions to the non-verbal disruptions in their
      body posture and conversational flow. The approach is illustrated using three
      case examples. In all three examples, the clients involved were able to reflect
      upon and re-organize conflicting goals that had been a source of significant
      emotional distress.

PMID- 22632764
TI  - High-throughput cellular screening of engineered ECM based on combinatorial
      polyelectrolyte multilayer films.
AB  - The capacity to engineer the extracellular matrix is critical to better
      understand cell function and to design optimal cellular environments to support
      tissue engineering, transplantation and repair. Stacks of adsorbed polymers can
      be engineered as soft wet three dimensional matrices, with properties tailored to
      support cell survival and growth. Here, we have developed a combinatorial method
      to generate coatings that self assemble from solutions of polyelectrolytes in
      water, layer by layer, to produce a polyelectrolyte multilayer (PEM) coating that
      has enabled high-throughput screening for cellular biocompatibility. Two
      dimensional combinatorial PEMs were used to rapidly identify assembly conditions
      that promote optimal cell survival and viability. Conditions were first piloted
      using a cell line, human embryonic kidney 293 cells (HEK 293), and subsequently
      tested using primary cultures of embryonic rat spinal commissural neurons. Cell
      viability was correlated with surface energy (wettability), modulus (matrix
      stiffness), and surface charge of the coatings.Our findings indicate that the
      modulus is a crucial determinant of the capacity of a surface to inhibit or
      support cell survival.

PMID- 22632765
TI  - Transdermal delivery of hyaluronic acid -- human growth hormone conjugate.
AB  - Hyaluronic acid (HA) is one of the major components of extracellular matrix
      (ECM). Keratinocyte and fibroblast are known to have HA receptors in the skin.
      Fibroblast also has human growth hormone (hGH) receptors. In this work, HA-hGH
      conjugate was developed as a receptor mediated transdermal delivery system of
      protein drugs. HA-hGH conjugate was synthesized by specific coupling reaction
      between aldehyde modified HA and the N-terminal amine group of hGH. We could
      confirm the proliferative effect of HA on keratinocyte and fibroblast, and the
      biological activity of HA-hGH conjugate in fibroblast with an elevated expression
      level of phosphorylated Janus kinase 2 (p-JAK2). Interestingly, fluorescence
      microscopy clearly visualized the dramatically enhanced penetration of HA-hGH
      conjugate through the dorsal skin of mice after topical treatment with FITC
      labeled HA-hGH conjugate. According to pharmacokinetic analysis, HA-hGH conjugate
      appeared to be delivered through the skin into the blood stream possibly by the
      receptor mediated transdermal delivery. This work confirms the feasibility of
      using the HA-hGH conjugate as a model system for the receptor mediated
      transdermal delivery of protein drugs and their further exploitation for various
      cosmetic and tissue engineering applications.

PMID- 22632766
TI  - Role of subnano-, nano- and submicron-surface features on osteoblast
      differentiation of bone marrow mesenchymal stem cells.
AB  - Subnano, nano and sub-micron surface features can selectively activate integrin
      receptors and induce osteoblast differentiation of bone marrow mesenchymal stem
      cells. Although it is widely accepted that nanoscale titanium surface roughness
      may promote differentiation of various osteoblast lineages, there has been no
      clear report on the threshold dimension of surface features and the optimized
      dimensions of surface features for triggering integrin activation and stem cell
      differentiation. This study systematically controlled titanium surface features
      from the sub-nano to sub-micron scales and investigated the corresponding effects
      on stem cell responses, such as integrin activation, cyclins, key transcriptional
      genes of osteoblast differentiation and osteoblastic phenotype genes. Surface
      features with sub-nano surface dimensions were insufficient to increase integrin
      activation compared to pure nanoscale titanium surface features. Although both
      pure nanoscale and nano-submicron hybrid scales of titanium surface features were
      sufficient for activating integrin-ligand proteins interactions through the alpha
      integrin subunits, only nano-submicron hybrid titanium surface features
      significantly accelerated subsequent osteoblast differentiation of primary mouse
      bone marrow stromal cells after 2 weeks. In addition, live cell analysis of human
      bone marrow mesenchymal stem cells on transparent titanium demonstrated rapid
      cytoskeletal re-organization on the nanoscale surface features, which ultimately
      induced higher expression of osteoblast phenotype genes after 3 weeks.

PMID- 22632767
TI  - Fiber reinforced calcium phosphate cements -- on the way to degradable load
      bearing bone substitutes?
AB  - Calcium phosphate cements (CPC) are well-established materials for the repair of
      bone defects with excellent biocompatibility and bioactivity. However,
      brittleness and low flexural/tensile strength so far restrict their application
      to non-load bearing areas. Reinforcement of CPC with fibers can substantially
      improve its strength and toughness and has been one major strategy to overcome
      the present mechanical limitations of CPC. Fiber reinforced calcium phosphate
      cements (FRCPC) thus bear the potential to facilitate the use of degradable bone
      substitutes in load bearing applications. This review recapitulates the state of
      the art of FRCPC research with focus on their mechanical properties and their
      biological evaluation in vitro and in vivo, including the clinical data that has
      been generated so far. After an overview on FRCPC constitutes and processing,
      some general aspects of fracture mechanics of reinforced cementitious composites
      are introduced, and their importance for the mechanical properties of FRCPC are
      highlighted. So far, fiber reinforcement leads to a toughness increase of up to
      two orders of magnitude. FRCPC have extensively been examined in vitro and in
      vivo with generally good results. While first clinical products focus on the
      improved performance of FRCPC with regard to secondary processing after injection
      such as fixation of screws and plates, first animal studies in load bearing
      applications show improved performance as compared to pure CPCs. Aside of the
      accomplished results, FRCPC bear a great potential for future development and
      optimization. Future research will have to focus on the selection and tailoring
      of FRCPC components, fiber-matrix compatibilization, integral composite design
      and the adjusted degradation behavior of the composite components to ensure
      successful long term behavior and make the composites strong enough for
      application in load bearing defects.

PMID- 22632768
TI  - Thiocarbamide and microwave-accelerated green methylation of cassava starch with
      dimethyl carbonate.
AB  - By combining the acceleration strategies of using thiocarbamide as a active
      catalyst, incorporating dimethyl carbonate (DMC) as a solvent and methylating
      reagent and applying microwave irradiation as energy resource, methylation of
      cassava starch can be performed efficiently to a high degree of substitution
      (DS=0.6) within 4 min. The structures of native cassava starch and methylated
      starch were characterized by (13)C NMR spectroscopy. Their thermal property and
      crystal structure were studied by thermogravimetric analysis (TG and DTG) and
      powder X-ray diffractometry.

PMID- 22632769
TI  - Measurement and analysis of the mannitol partition coefficient in sucrose
      crystallization under simulated industrial conditions.
AB  - Mannitol is a major deterioration product of Leuconstoc mesenteroides bacterial
      metabolism of sucrose and fructose from both sugarcane and sugar beet. The effect
      of crystallization conditions on the mannitol partition coefficient (K(eff))
      between impure sucrose syrup and crystal has been investigated in a batch
      laboratory crystallizer and a batch pilot plant-scale vacuum pan. Laboratory
      crystallization was operated at 65.5 degrees C (150 degrees F), 60.0 degrees C
      (140 degrees F), and 51.7 degrees C (125 degrees F) with a 78.0 Brix (%
      refractometric dissolved solids) pure sucrose syrup containing 0%, 0.1%, 0.2%,
      1.0%, 2.0%, 3.0%, and 10% (at 65.5 degrees C only) mannitol on a Brix basis.
      Produced mother liquor and crystals were separated by centrifugation and their
      mannitol contents measured by ion chromatography with integrated pulsed
      amperometric detection (IC-IPAD). The extent of mannitol partitioning into the
      crystals depended strongly on the mannitol concentration in the feed syrup and,
      to a lesser extent, the crystallization temperature. At 65.5 and 60.0 degrees C,
      the K(eff) varied from ~0.4% to 3.0% with 0.2% to 3.0% mannitol in the feed
      syrup, respectively. The mannitol K(eff) was lower than that reported for dextran
      (~9-10% K(eff)), another product of Leuconstoc deterioration, under similar
      sucrose crystal growth conditions. At 10% mannitol concentration in the syrup at
      65.5 degrees C, co-crystallization of mannitol with sucrose occurred and the
      crystal growth rate was greatly impeded. In both laboratory and pilot plant
      crystallizations (95.7% purity; 78.0 Brix; 65.5 degrees C), mannitol tended to
      cause conglomerates to form, which became progressively worse with increased
      mannitol syrup concentration. At the 3% mannitol concentration, crystallization
      at both the laboratory and pilot plant scales was more difficult. Mannitol
      incorporation into the sucrose crystal results mostly from liquid syrup
      inclusions but adsorption onto the crystal surface may play a minor role at lower
      mannitol concentrations.

PMID- 22632770
TI  - Preface--biocatalysis.

PMID- 22632771
TI  - Surgical management of early-stage non-small cell lung carcinoma and the present
      and future roles of adjuvant therapy: a review for the radiation oncologist.
AB  - We review the evidence for optimal surgical management and adjuvant therapy for
      patients with stages I and II non-small cell lung cancer (NSCLC) along with
      factors associated with increased risks of recurrence. Based on the current
      evidence, we recommend optimal use of mediastinal lymph node dissection, adjuvant
      chemotherapy, and post-operative radiation therapy, and make suggestions for
      areas to explore in future prospective randomized clinical trials.

PMID- 22632772
TI  - Dose-guided radiotherapy: potential benefit of online dose recalculation for
      stereotactic lung irradiation in patients with non-small-cell lung cancer.
AB  - PURPOSE: To determine whether dose-guided radiotherapy (i.e., online
      recalculation and evaluation of the actual dose distribution) can improve
      decision making for lung cancer patients treated with stereotactic body
      radiotherapy. METHODS AND MATERIALS: For this study 108 cone-beam computed
      tomography (CBCT) scans of 10 non-small-cell lung cancer patients treated with
      stereotactic body radiotherapy were analyzed retrospectively. The treatment plans
      were recalculated on the CBCT scans. The V(100%) of the internal target volume
      (ITV) and D(max) of the organs at risk (OARs) were analyzed. Results from the
      recalculated data were compared with dose estimates for target and OARs by
      superposition of the originally planned dose distribution on CBCT geometry (i.e.,
      the original dose distribution was assumed to be spatially invariant). RESULTS:
      Before position correction was applied the V(100%) of the ITV was 100% in 65% of
      the cases when an ITV-PTV margin of 5 mm was used and 52% of the cases when a
      margin of 3 mm was used. After position correction, the difference of D(max) in
      the OARs with respect to the treatment plan was within 5% in the majority of the
      cases. When the dose was not recalculated but estimated assuming an invariant
      dose distribution, clinically relevant errors occurred in both the ITV and the
      OARs. CONCLUSION: Dose-guided radiotherapy can be used to determine the actual
      dose in OARs when the target has moved with respect to the OARs. When the
      workflow is optimized for speed, it can be used to prevent unnecessary position
      corrections. Estimating the dose by assuming an invariant dose instead of
      recalculation of the dose gives clinically relevant errors.

PMID- 22632773
TI  - Resident liability in medical malpractice.

PMID- 22632774
TI  - Does antibiotic prophylaxis prevent meningitis in patients with basilar skull
      fracture?

PMID- 22632775
TI  - Cardiac evaluation for structural abnormalities may not be required in patients
      presenting with syncope and a normal ECG result in an observation unit setting.
AB  - STUDY OBJECTIVE: Patients with syncope are frequently managed in observation
      units and receive serial examinations, monitoring for arrhythmias, and structural
      analysis of the heart. The primary aim of this study is to determine the utility
      of structural analysis of the heart in syncope patients who are being managed in
      an observation unit and have a normal ECG result. METHODS: This is a
      retrospective, observational chart review of all consecutive adult patients
      observed during 18 months at an urban, academic medical center. A case report
      form with demographics, ECG interpretations, and structural analysis of the heart
      data was generated and all variables were defined before data extraction.
      Subjects with an ECG demonstrating any arrhythmia, premature atrial contraction,
      premature ventricular contraction, pacing, second- and third-degree blocks, and
      left bundle branch block were excluded from the normal ECG group. An abnormal
      cardiac structure was defined as an ejection fraction less than 45%, severe
      hypertrophy, or severe valvular abnormality. Ten percent of cases were evaluated
      by a second extractor to verify accuracy. Descriptive statistics with confidence
      intervals (CIs) and interquartile ranges (IQRs; 25%, 75%) are used. RESULTS:
      Three hundred twenty-three subjects were managed in the observation unit for
      syncope, 48% were men, and their median age was 66 years (25%, 75% IQR 52, 80).
      Two of 323 (0.6%; 95% CI 0.2% to 2.2%) had an arrhythmia; 1 of 323 had a non-ST
      segment myocardial infarction (0.3%; 95% CI 0.1% to 1.7%). Of the 323 patients,
      267 had a normal ECG result and 235 (88%) had their cardiac structure evaluated.
      Forty-eight percent of the normal ECG group were men, and the median age was 65
      years (25%, 75% IQR 52, 79). Zero of 235 patients (0%; 95% CI 0% to 1.6%) had a
      structural abnormality identified on evaluation, and 2 of 18 (11%; 95% CI 3.1% to
      32.8%) had an abnormal stress echocardiogram result. CONCLUSION: Structural
      abnormalities are unlikely in syncope patients with a normal ECG result. Care
      should focus on excluding arrhythmias and acute coronary syndrome.

PMID- 22632776
TI  - Influence of adaptive analysis on unnecessary patient recruitment: reanalysis of
      the RATPAC trial.
AB  - STUDY OBJECTIVE: Recruitment to clinical trials is a challenging but essential
      activity in emergency medicine. Conventional fixed-sample trials may continue to
      recruit patients after efficacy has been demonstrated or when further recruitment
      is futile. Adaptive trials make use of emerging information to modify aspects of
      a trial or terminate it prematurely, potentially resulting in savings in terms of
      sample size, time, and cost. We aim to use sequential testing procedures to
      reanalyze data from a fixed-sample trial, the Randomised Assessment of Treatment
      Using Panel Assay of Cardiac Markers (RATPAC) trial, and investigate the
      potential for adaptive designs to reduce unnecessary recruitment. METHODS: The
      trial was reanalyzed with a triangular group sequential design, with interim
      analyses planned every 3 months. Patients were analyzed in the order in which
      they entered the original trial. RESULTS: We found that the RATPAC trial could
      potentially have stopped 1 year earlier, with 722 patients enrolled compared with
      2,243 patients in the original trial, making a potential saving of approximately
      $390,000. Estimates of effect were similar, and the qualitative conclusions of
      the original and group sequential RATPAC trials were in agreement. However, the
      group sequential approach is not without limitations and would have resulted in
      less precise estimates of effect and less information available for the
      subsequent evaluation of secondary endpoints. CONCLUSION: Sequential designs are
      well suited in emergency medicine because of the rapidly obtained outcomes and
      the need to avoid unnecessary recruitment. We recommend that group sequential
      designs be considered for clinical trials in emergency medicine.

PMID- 22632777
TI  - No significant association of aspirin use with cerebral microbleeds in the
      asymptomatic elderly.
AB  - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) may predict future risk for
      intracerebral hemorrhage (ICH). ICH is one of the most important complications of
      aspirin use. The association between aspirin use and CMBs is still controversial.
      In this context, we sought to investigate whether aspirin use is associated with
      CMBs in subjects without previous history of stroke. METHODS: Asymptomatic
      elderly subjects (n=1452; age >= 65 years) who visited for routine health check
      ups were included in this study. CMBs were evaluated through T2*-weighted
      gradient-recalled echo MRI. Information about aspirin or warfarin use was
      obtained using a structured questionnaire. RESULTS: A total of 138 subjects
      (9.5%) were found to have CMBs. In the group of aspirin use, 43 subjects (11.2%)
      had CMBs; among them 9 (2.3%) had strictly lobar microbleeds and 34 (8.9%) had
      deep or infratentorial microbleeds. Compared with the non-use group, the risk for
      CMBs did not increase in the group of aspirin use (adjusted odds ratio, 1.10; 95%
      confidence interval, 0.73-1.66). For the group of aspirin use above 5 years, the
      proportion of CMBs (11.1%) did not increase compared with the group of short-term
      use (<= 5 years, 9.5%, p=0.99) and non-use group (8.9%, p=0.66). CONCLUSIONS: We
      found that the prevalence of CMBs did not increase in the group of aspirin use,
      and the presence of CMBs was not associated with the duration of aspirin use in
      asymptomatic elderly subjects without a history of stroke or transient ischemic
      attack.

PMID- 22632778
TI  - Neuromyelitis optica in a patient with pemphigus foliaceus.
AB  - Neuromyelitis optica (NMO, also eponymously known as Devic's disease) is an
      immune-mediated demyelinating disease of the central nervous system that can lead
      to significant disability. Pediatric NMO is a rare disorder often reported after
      an infection. The authors report a 16 year-old female patient with pemphigus
      foliaceus who developed subacute optic neuritis followed by cervical transverse
      myelitis. Restricted distribution of the lesions in the optic nerve and spinal
      cord was confirmed by ophthalmological evaluation and magnetic resonance imaging
      of the brain and spinal cord. She was started on intravenous methylprednisolone
      and then given a maintenance oral prednisone. Subsequently, she was treated with
      a nonsteroidal immunosuppressant, mycophenolate mofetil, with a target dose of
      1000 mg twice a day. Over the course of months, patient noted significant
      recovery of previous deficits and resolution of the cervical cord enhancement,
      expansion and cystic dilatation that was previously seen. This case is noteworthy
      for being the first patient reported with neuromyelitis optica associated with
      pemphigus foliaceus.

PMID- 22632779
TI  - Enteroviral encephalitis presenting as rapidly progressive aphasia.
AB  - Enteroviral CNS infection is common and its clinical course is usually benign. In
      immunocompromised patients, however, it can cause meningoencephalitis, presenting
      with altered mentality and seizure. We describe a previously healthy female
      patient with enteroviral meningoencephalitis who showed rapidly progressive
      aphasia. Examination of her cerebrospinal fluid (CSF) showed pleocytosis with
      lymphocyte dominance, elevated protein, and normal glucose, findings compatible
      with viral encephalitis. Fluid-attenuated inversion recovery (FLAIR) brain MRI
      showed hyperintensity in the left frontal and parietal cortices. Enterovirus in
      the CSF was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR)
      of the CSF. Although her neurological deficits had progressed to global aphasia,
      conservative management resulted in complete improvement within 3 months. This
      case provides unusual clinical manifestations and imaging findings in enteroviral
      encephalitis.

PMID- 22632780
TI  - Mitochondrial myopathy due to novel missense mutation in the cytochrome c oxidase
      1 gene.
AB  - We report a novel heteroplasmic mutation p.Y440C in the mitochondrial DNA-encoded
      subunit I of the cytochrome c oxidase (COX) gene in a patient with late onset
      progressive painless weakness. Her muscle biopsy showed scattered COX-negative
      fibers and several small collections of inflammatory cells. The mutation was
      detected in the patient's muscle but not in her blood. The low mutant load in
      muscle could explain the patient's late onset of the myopathy and milder
      phenotype when compared to the previously published cases with MTCO1 mutations.

PMID- 22632781
TI  - Severity of restless legs syndrome is inversely correlated with echogenicity of
      the substantia nigra in different neurodegenerative movement disorders. a
      preliminary observation.
AB  - OBJECTIVE: Hyperechogenicity of the substantia nigra is a frequent observation on
      transcranial sonography in Parkinson's disease and Machado-Joseph disease
      patients. Additionally, restless legs syndrome is a sleep disorder that is also
      frequently found in both diseases. Autopsy studies have demonstrated increased SN
      iron content in hyperechogenic substantia nigra. Iron storage is also known to be
      involved in restless legs syndrome. We formally compared echogenicity of the
      substantia nigra with restless legs syndrome in Parkinson's disease and Machado
      Joseph disease patients. METHODS: Transcranial brain sonography was performed in
      a sample of Parkinson's disease and Machado-Joseph disease patients, and findings
      then correlated with the presence and severity of restless legs syndrome.
      RESULTS: There was a continuum of substantia nigra echogenicity among groups
      (Parkinson's disease versus Machado-Joseph disease versus controls) and sub
      groups (Parkinson's disease with and without restless legs syndrome versus
      Machado-Joseph disease with and without restless legs syndrome) as well as a
      statistically significant negative correlation between restless legs syndrome
      severity and substantia nigra echogenicity (p<0.001). CONCLUSIONS: These
      preliminary observations demonstrate that the severity of RLS may be influenced
      by nigral iron load reflected by substantia nigra echogenicity in different
      neurodegenerative movement disorders.

PMID- 22632782
TI  - Plasma levodopa peak delay and impaired gastric emptying in Parkinson's disease.
AB  - OBJECTIVES: Whereas delayed gastric emptying is believed to be a causative factor
      for producing delayed-on and motor fluctuation in Parkinson's disease (PD), few
      studies have directly measured levodopa pharmacodynamics and gastric emptying
      together. In order to determine the relationship, we measured these two
      parameters in a single PD patients cohort. METHODS: Thirty-one patients with PD
      were enrolled in the study. They were 11 men and 20 women; age, 68.1 +/- 7.8
      years; disease duration, 4.2 +/- 3.8 years; Unified Parkinson's Disease Rating
      Scale Part 3 Motor Score 18.37 +/- 8.60; bowel movement <3 times a week in 20;
      all taking 301 mg +/- 94 mg/day levodopa/carbidopa. All patients underwent
      levodopa pharmacokinetic study and the gastric emptying study using (13)C
      octanoic acid expiration breath test. Statistical analysis was performed by
      Student's t-test and Mann-Whitney's U test. RESULTS: Pharmacokinetic study showed
      that the plasma levodopa peak was at 2 hours in 42% (13/31 patients) whereas at 1
      hour in 58% (18/31 patients), total of 50.7 +/- 16.4 min (mean +/- standard
      deviation) in all 31 patients. The gastric emptying study showed that T(max)
      ((13)C)>60 min was more common in patients with a plasma levodopa peak at 2 hours
      (14/18, 69%) than in those with a plasma levodopa peak at 1 hour (4/13, 22%)
      (p<0.05), total of 50.7 +/- 16.4 min in all 31 patients. CONCLUSION: We found a
      significant relationship between levodopa pharmacokinetics and gastric emptying
      in PD patients, suggesting that delayed gastric emptying is a causative factor
      for producing delayed-on in PD. Therefore, studies of improved gastric emptying
      in order to ameliorate delayed-on in PD are warranted.

PMID- 22632783
TI  - Clinical and pathological heterogeneity in a series of 31 patients with IgM
      related neuropathy.
AB  - BACKGROUND: IgM-related neuropathy generally presents as a late-onset
      demyelinating polyneuropathy with predominant sensory loss and ataxia. Sporadic
      cases with atypical presentation have been described. PATIENTS AND METHODS: We
      report clinical and pathological findings from 31 patients with IgM-related
      neuropathy followed in our Institute of Neurology over a 20-year period. RESULTS:
      Typical presentation with predominant sensory ataxic neuropathy was observed in
      18/31 patients. In the remaining 13/31 (42%), we observed an atypical phenotype,
      characterized by multiple mononeuropathy or polyneuropathy with predominant motor
      impairment; one patient had polyneuropathy with predominant small-fibre
      involvement. Uncommon pathological findings consisting in inflammatory
      infiltrates, focal axonal loss or light chain deposition were observed in 8
      patients, all with atypical clinical phenotype. Almost all patients with atypical
      phenotype improved with immunosuppressive therapy. CONCLUSIONS: A significant
      proportion of patients with IgM-related neuropathy presents with atypical
      clinical features. In these patients, sural nerve biopsy helps clarify
      heterogeneous disease mechanisms and identify patients who might benefit from
      immunosuppressive therapy.

PMID- 22632785
TI  - [Medical devices needed for stereotactic radiosurgery and intracranial
      stereotactic radiotherapy].
AB  - Since the previous special issue of Cancer Radiotherapie dedicated to
      radiosurgery in 1998, many important technological and computer developments have
      improved external beam radiotherapy treatment device performances. Whereas the
      Gamma Knife((r)) was the gold standard for intracranial radiosurgery, new linear
      accelerator developments have led to new possibilities for the clinicians. This
      article describes quickly the different devices available for cranial
      radiosurgery or fractionated stereotactic radiotherapy.

PMID- 22632786
TI  - [Ballistic quality assurance].
AB  - This review describes the ballistic quality assurance for stereotactic
      intracranial irradiation treatments delivered with Gamma Knife(r) either
      dedicated or adapted medical linear accelerators. Specific and periodic controls
      should be performed in order to check the mechanical stability for both
      irradiation and collimation systems. If this step remains under the
      responsibility of the medical physicist, it should be done in agreement with the
      manufacturer's technical support. At this time, there are no recent published
      guidelines. With technological developments, both frequency and accuracy should
      be assessed in each institution according to the treatment mode: single versus
      hypofractionnated dose, circular collimator versus micro-multileaf collimators.
      In addition, "end-to-end" techniques are mandatory to find the origin of
      potential discrepancies and to estimate the global ballistic accuracy of the
      delivered treatment. Indeed, they include frames, non-invasive immobilization
      devices, localizers, multimodal imaging for delineation and in-room positioning
      imaging systems. The final precision that could be reasonably achieved is more or
      less 1mm.

PMID- 22632787
TI  - The contribution of waste water treatment plants to PBDEs in ambient air.
AB  - Air samples were collected at different sites in and around two wastewater
      treatment plants (WWTPs) located in central Italy to determine the
      concentrations, compositional profiles and contribution to ambient levels of
      eight polybrominated diphenyl ethers (PBDEs). The investigated WWTPs were
      selected as they treat industrial wastewater produced by local textile industries
      along with municipal wastewater. PBDE concentrations within the WWTPs were higher
      than those measured at reference sites located 4 and 5 km away with BDE-209
      dominating the BDE congener composition in all air samples in 2008. Ambient PBDE
      concentrations measured in and around the WWTPs and estimates of emissions from
      aeration tanks suggest that WWTPs are sources of PBDEs to ambient air. Principal
      component analysis and Pearson correlations confirmed this result. The effect of
      distance from the plant and wind direction on atmospheric concentrations was also
      investigated. Although the primary fate of PBDEs in WWTPs will be partitioning to
      sewage sludge, this study suggests that plants can provide a measurable source of
      these compounds to local ambient air.

PMID- 22632788
TI  - Interactions between indoor and outdoor air pollution--trends and scientific
      challenges.

PMID- 22632793
TI  - Morita-Baylis-Hillman adducts: biological activities and potentialities to the
      discovery of new cheaper drugs.
AB  - This review aims to present by the first time the Morita-Baylis-Hillman adducts
      (MBHA) as a new class of bioactive compounds and highlight its potentialities to
      the discovery of new cheaper and efficient drugs. Now, most these compounds can
      be prepared fast and on a single synthetic step (one-pot reaction) in high yields
      and using ecofriendly synthetic protocols. We highlight here the aromatic MBHA,
      which have shown diverse biological activities as anti-Leishmania chagasi and
      Leishmania amazonensis (parasites that cause cutaneous and visceral
      leishmaniasis), anti-Trypanosoma cruzi (parasite that cause Chagas disease), anti
      Plasmodium falciparum and Plasmodium berghei (parasites that cause malaria),
      lethal against Biomphalaria glabrata (the snail transmitter of schistosomiasis),
      antibacterial, antifungal, herbicide and actives against some human tumor cell
      lines. Understanding of the biological mechanisms of action of this new class of
      molecules is still in the infancy stage. However, we report here which has been
      described to date on the possibilities of biological mechanisms of action, and we
      present new analyzes based on literature in this area. The academic and
      industrial interest in selecting green and cheaper experiments to the drugs
      development has been the prime mover of the growth on the subject.

PMID- 22632792
TI  - Inhibitors of Dengue virus and West Nile virus proteases based on the
      aminobenzamide scaffold.
AB  - Dengue and West Nile viruses (WNV) are mosquito-borne members of flaviviruses
      that cause significant morbidity and mortality. There is no approved vaccine or
      antiviral drugs for human use to date. In this study, a series of functionalized
      meta and para aminobenzamide derivatives were synthesized and subsequently
      screened in vitro against Dengue virus and West Nile virus proteases. Four active
      compounds were identified which showed comparable activity toward the two
      proteases and shared in common a meta or para(phenoxy)phenyl group. The
      inhibition constants (K(i)) for the most potent compound 7n against Dengue and
      West Nile virus proteases were 8.77 and 5.55 MUM, respectively. The kinetics data
      support a competitive mode of inhibition of both proteases by compound 7n. This
      conclusion is further supported by molecular modeling. This study reveals a new
      chemical scaffold which is amenable to further optimization to yield potent
      inhibitors of the viral proteases via the combined utilization of iterative
      medicinal chemistry/structure-activity relationship studies and in vitro
      screening.

PMID- 22632794
TI  - Objective assessment of pediatric voice disorders with the acoustic voice quality
      index.
AB  - OBJECTIVES/HYPOTHESIS: Instrumental measures of voice allow practitioners to
      assess the severity of voice disorders and objectively measure treatment
      outcomes. Instrumental measures should be calculated on both sustained vowel and
      connected speech samples to ensure ecological validity. However, there is a lack
      of appropriate, validated acoustic measurements for use in the pediatric
      population. The Acoustic Voice Quality Index (AVQI) is a multivariate acoustic
      measure of dysphonia that has been found to be reliable, valid, and have
      diagnostic accuracy and response to change in an adult population. This study
      aimed to evaluate the AVQI in a pediatric population. STUDY DESIGN: This study
      was a prospective observational study of a sample of dysphonic and normophonic
      children. METHODS: Sixty-seven preterm participants (born at less than 25 weeks
      gestation) aged between 6 and 15 years were recruited. Participants were excluded
      because of either inability to comply with task requirements or other speech
      related factors that affected acoustic measurement. Forty normophonic term-born
      participants aged between 5 and 15 years were also recruited. AVQI analysis was
      conducted on a prolonged vowel sample and a sample of continuous speech. RESULTS:
      The AVQI was found to have diagnostic accuracy and specificity in this population
      of children with and without dysphonia. It was moderately correlated with ratings
      of severity on the GRBAS (overall grade of hoarseness (G), roughness (R),
      breathiness (B), aesthenicity (A), and strain (S)), a subjective rating scale.
      The threshold for pathology of this sample of 3.46 showed strong sensitivity,
      specificity, and accuracy, with good-to-excellent likelihood ratios. CONCLUSIONS:
      This study found that the AVQI has diagnostic accuracy in a pediatric population,
      suggesting that it is an appropriate assessment tool to determine the presence
      and severity of pediatric voice disorders.

PMID- 22632795
TI  - Analysis of vocal fold function from acoustic data simultaneously recorded with
      high-speed endoscopy.
AB  - SUMMARY: Acoustic and endoscopic voice assessments are routinely performed to
      determine the vocal fold vibratory function as part of the voice assessment
      protocol in clinics. More often than not these data are separately recorded,
      resulting in information being obtained from two different phonation segments and
      an increase of time for the voice evaluation process. This study explores the use
      of acoustic data, simultaneously recorded during high-speed endoscopy (HSE), for
      the evaluation of vocal fold function. PATIENTS AND METHODS: HSE and acoustic
      data were recorded from the subjects simultaneously during sustained phonation.
      The data included voices of 73 healthy subjects, 148 paresis, 210 functional
      dysphonias, and 119 benign lesions of vocal folds. For this study, only acoustic
      data were analyzed using Dr. Speech software (Tiger electronics Inc., MA). Twelve
      parameters were computed; 82% of the acoustic voice recordings could be analyzed.
      Statistical analysis was performed with SPSS 17.0. RESULTS: Acoustic data was
      easily recorded simultaneously allowing analyses of the same phonation segment to
      determine vocal fold function and therefore eliminating the need for another
      voice recording. The acoustic voice parameters differed between genders in the
      healthy voice group. Most of the parameters showed significant differences
      between healthy and pathological groups. CONCLUSION: Simultaneously recorded
      endoscopic and acoustic data is valuable. Differentiation between healthy and
      pathological groups was possible using acoustic data only. We suggest that the
      synchronously recorded acoustic signal is of sufficient quality for objective
      analysis yielding reduced examination time.

PMID- 22632797
TI  - The Great Recession, somatic symptomatology and alcohol use and abuse.
AB  - While most research has examined the long-term effects of alcohol consumption on
      health, the current study examines how health status impacts on drinking
      behavior. Using data from a national study conducted between 2010 and 2011 to
      assess the impact of the recession on drinking behavior, this study examines how
      economic hardships linked to the recent economic recession affect physical
      health, and how physical health may in turn affect alcohol use. Structural
      equation models were used to test the predicted associations. The data
      demonstrate that many of the economic stressors linked to the recession are
      associated with increased somatic symptoms. Somatic symptoms are also associated
      with increased drinking for men, but not for women. These findings suggest that
      men may use alcohol to self medicate somatic symptomatology. The current findings
      are consistent with gender role-based explanations that account for gender
      disparities in the utilization of medical care.

PMID- 22632798
TI  - Comparison of the effects of different anesthetic techniques on
      electrocorticography in patients undergoing epilepsy surgery - a bispectral index
      guided study.
AB  - AIM: It is well known that general anesthetics suppress/alter
      electrocorticography (ECoG) activity. However there are no randomized studies
      available, comparing various anesthetic techniques as regards their effects on
      ECoG. METHODS: The following is a double blind, randomized cross over study to
      compare the effects of isoflurane and propofol with or without nitrous oxide on
      electrocorticographic activity in patients undergoing epilepsy surgery. 40
      patients suffering from medically intractable epilepsy scheduled to undergo
      resective surgery under ECoG guidance under general anesthesia, (March 2008
      December 2010) were enrolled. Patients received either isoflurane or propofol
      (with air/oxygen or nitrous oxide/oxygen) as maintenance agents as per
      randomization and ECoG was recorded and quantified as per a scoring system (range
      1-5, where 5 is most abnormal). RESULTS: The mean ECoG score in isoflurane group
      and propofol with nitrous oxide was 3.0(1.2), 3.2(1.2) [p=0.7] and with air was
      3.9(1.0) and 3.4(1.1) [p=0.1] respectively. In both isoflurane group and propofol
      group addition of nitrous oxide depressed the ECoG score (p <= 0.01, 0.5
      respectively). The total duration of anesthesia, surgery, emergence time,
      extubation time, and hospital stay was comparable in two groups. CONCLUSION: In
      our study optimal ECoG recordings were possible with use of either isoflurane or
      propofol. Addition of nitrous oxide to either of the anesthetic regimens
      suppressed the ECoG score.

PMID- 22632799
TI  - The ciliopathies: a transitional model into systems biology of human genetic
      disease.
AB  - The last decade has witnessed an explosion in the identification of genes,
      mutations in which appear sufficient to cause clinical phenotypes in humans. This
      is especially true for disorders of ciliary dysfunction in which an excess of 50
      causal loci are now known; this discovery was driven partly by an improved
      understanding of the protein composition of the cilium and the co-occurrence of
      clinical phenotypes associated with ciliary dysfunction. Despite this progress,
      the fundamental challenge of predicting phenotype and or clinical progression
      based on single locus information remains unsolved. Here, we explore how the
      combinatorial knowledge of allele quality and quantity, an improved understanding
      of the biological composition of the primary cilium, and the expanded
      appreciation of the subcellular roles of this organelle can be synthesized to
      generate improved models that can explain both causality but also variable
      penetrance and expressivity.

PMID- 22632800
TI  - Development and validation of a risk calculator for prediction of mortality after
      infrainguinal bypass surgery.
AB  - OBJECTIVE: For peripheral arterial disease, infrainguinal bypass grafting (BPG)
      carries a higher perioperative risk compared with peripheral endovascular
      procedures. The choice between the open and endovascular therapies is to an
      extent dependent on the expected periprocedural risk associated with each. Tools
      for estimating the periprocedural risk in patients undergoing BPG have not been
      reported in the literature. The objective of this study was to develop and
      validate a calculator to estimate the risk of perioperative mortality <=30 days
      of elective BPG. METHODS: We identified 9556 patients (63.9% men) who underwent
      elective BPG from the 2007 to 2009 National Surgical Quality Improvement Program
      data sets. Multivariable logistic regression analysis was performed to identify
      risk factors associated with 30-day perioperative mortality. Bootstrapping was
      used for internal validation. The risk factors were subsequently used to develop
      a risk calculator. RESULTS: Patients had a median age of 68 years. The 30-day
      mortality rate was 1.8% (n = 170). Multivariable logistic regression analysis
      identified seven preoperative predictors of 30-day mortality: increasing age,
      systemic inflammatory response syndrome, chronic corticosteroid use, chronic
      obstructive pulmonary disease, dependent functional status, dialysis dependence,
      and lower extremity rest pain. Bootstrapping was used for internal validation.
      The model demonstrated excellent discrimination (C statistic, 0.81; bias
      corrected C statistic, 0.81) and calibration. The validated risk model was used
      to develop an interactive risk calculator using the logistic regression equation.
      CONCLUSIONS: The validated risk calculator has excellent predictive ability for
      30-day mortality in a patient after an elective BPG. It is anticipated to aid in
      surgical decision making, informed patient consent, preoperative optimization,
      and consequently, risk reduction.

PMID- 22632801
TI  - Long-range Ca2+ waves transmit brain-damage signals to microglia.
AB  - Microglia are the resident phagocytes of the brain that are responsible for the
      clearance of injured neurons, an essential step in subsequent tissue
      regeneration. How death signals are controlled both in space and time to attract
      these cells toward the site of injury is a topic of great interest. To this aim,
      we have used the optically transparent zebrafish larval brain and identified
      rapidly propagating Ca2+ waves that determine the range of microglial responses
      to neuronal cell death. We show that while Ca2+-mediated microglial responses
      require ATP, the spreading of intercellular Ca2+ waves is ATP independent.
      Finally, we identify glutamate as a potent inducer of Ca2+-transmitted microglial
      attraction. Thus, this real-time analysis reveals the existence of a mechanism
      controlling microglial targeted migration to neuronal injuries that is initiated
      by glutamate and proceeds across the brain in the form of a Ca2+ wave.

PMID- 22632802
TI  - MT1-MMP inactivates ADAM9 to regulate FGFR2 signaling and calvarial osteogenesis.
AB  - MMP14 encodes a membrane-tethered metalloproteinase MT1-MMP, capable of
      remodeling the extracellular matrix and modulating receptors on the cell surface.
      Loss of MT1-MMP results in craniofacial abnormalities. Here we show that MT1-MMP
      forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically
      inactivates ADAM9, hence protecting FGFR2 from ADAM9-mediated ectodomain shedding
      on the cell surface. In Mmp14-/- osteoblasts, FGF-induced proliferation and
      downstream signaling are specifically compromised, in conjunction with ADAM9
      upregulation and FGFR2 shedding. The retarded parietal growth in Mmp14-/- embryos
      starts at 15.5 dpc, attributable to the impaired FGFR2 signaling due to increased
      shedding mediated by ADAM9. Adam9 depletion completely rescues the defective
      FGFR2 signaling and largely restores calvarial bone growth in Mmp14-/- embryos.
      These data reveal a regulatory paradigm for FGRF2 signaling and identify MT1-MMP
      as a critical negative modulator of ADAM9 activity to maintain FGFR2 signaling in
      calvarial osteogenesis.

PMID- 22632803
TI  - Lumbopelvic fixation for multiplanar sacral fractures with spinopelvic
      instability.
AB  - Sacral fractures with both transverse and bilateral vertical fracture components
      are by definition multiplanar fractures, and often present with spinopelvic
      instability and cauda equina deficits. The treatment is challenging. Between 2006
      and 2009, we treated nine such patients at our trauma centre. There were six men
      and three women, with a mean age of 32.2 years. Preoperative neurologic deficits
      were noted in seven patients; four patients had complete cauda equina paralysis,
      and three patients had incomplete cauda equina syndrome. All patients were
      treated using lumbopelvic instrumented fixation without other devices for their
      multiplanar sacral fractures. Six patients who had neurological deficits and
      sacral canal compression underwent decompression laminectomy. The mean
      postoperative follow-up time was 21.7 months (range, 14-32 months). All fractures
      went on to union without loss of reduction or hardware failure. The mean Gibbons
      score improved from 3.5 preoperatively to 2.3 postoperatively among the patients
      who underwent decompression laminectomy. Eight out of nine patients had fair or
      better results based on radiographic criteria and the Majeed pelvic fracture
      outcome score. Our experience suggests lumbopelvic fixation can be used for the
      treatment of multiplanar sacral fractures with spinopelvic instability with a low
      rate of complications. Neurologic improvement can be expected, but whether
      surgical decompression results in substantially better neurologic recovery than
      conservative treatment remains uncertain.

PMID- 22632804
TI  - Canadian Ophthalmological Society evidence-based clinical practice guidelines for
      the management of diabetic retinopathy.

PMID- 22632806
TI  - Chorangiocarcinoma of the placenta: a case report and clinical review.
AB  - OBJECTIVE: We describe a case of chorangiocarcinoma, a complex lesion consisting
      of a trophoblastic proliferation within a chorangioma, presenting in a term
      placenta. MATERIALS AND METHODS: The lesion was diagnosed by ultrasound at a
      second trimester check-up after amniocentesis, performed because of increased
      combined risk at first trimester screening for trisomy 21. After uncomplicated
      vaginal delivery, a healthy child was born and the placenta was expelled
      spontaneously. RESULTS: Gross examination of the placenta showed a well
      demarcated mass, bulging paracentrally from the fetal surface. Histology revealed
      a trophoblastic proliferation inside a chorangioma, consisting of multiple
      nodules with characters of focal multinucleation and pleomorphic cell nuclei,
      extensive central necrosis and high mitotic activity. Immunohistochemical
      staining showed strong intensity for hCG; Ki-67 (MIB-1) demonstrated a high
      proliferation index. Histopathological and immunohistochemical profile was
      compatible with a malignant trophoblastic proliferation. CONCLUSIONS: This is
      only the fifth reported case of so-called "chorangiocarcinoma" of the placenta
      (Table 1). However, histopathologically only one reported case was identical to
      ours. A proliferation of atypical trophoblast was observed inside a chorangioma,
      which formed as it were a shield around the trophoblast. No extravascular stromal
      invasion was present. Follow-up revealed no metastases, either in the mother or
      the child, up to 3 months after birth.

PMID- 22632807
TI  - Outcomes associated with intradialytic oral nutritional supplements in patients
      undergoing maintenance hemodialysis: a quality improvement report.
AB  - BACKGROUND: Insufficient clinical data exist to determine whether provision of
      oral nutritional supplements during dialysis can improve survival in
      hypoalbuminemic maintenance hemodialysis patients. STUDY DESIGN: Retrospective
      matched-cohort study. SETTING & PARTICIPANTS: All oral nutritional supplement
      program-eligible in-center maintenance hemodialysis patients with albumin level
      <=3.5 g/dL in quarter 4 of 2009 without oral nutritional supplements in the prior
      90 days at Fresenius Medical Care, North America facilities. QUALITY IMPROVEMENT
      PLAN: Monitored intradialytic oral nutritional supplements were provided to
      eligible maintenance hemodialysis patients upon physician order, to continue for
      a year or until serum albumin level was >=4.0 g/dL. OUTCOME: Mortality (including
      deaths and withdrawals), followed up until December 31, 2010. MEASUREMENTS: Both
      an intention-to-treat (ITT) and an as-treated analysis was performed using a 1:1
      geographic region and propensity score-matched study population (using case-mix,
      laboratory test, access type, 30-day prior hospitalization, and incident patient
      status) comparing patients treated with intradialytic oral nutritional
      supplements with usual-care patients. Cox models were constructed, unadjusted and
      adjusted for facility standardized mortality ratio and case-mix and laboratory
      variables. RESULTS: The ITT and as-treated analyses both showed lower mortality
      in the oral nutritional supplement group. The conservative ITT models with 5,227
      matched pairs had 40% of controls subsequently receiving oral nutritional
      supplements after January 1, 2010 (because many physicians delayed
      participation), with comparative death rates of 30.1% versus 30.4%. The
      corresponding as-treated (excluding crossovers) death rates for 4,289 matched
      pairs were 30.9% versus 37.3%. The unadjusted ITT mortality HR for oral
      nutritional supplement use was 0.95 (95% CI, 0.88-1.01), and the adjusted HR was
      0.91 (95% CI, 0.85-0.98); the corresponding as-treated HRs were 0.71 (95% CI,
      0.66-0.76) and 0.66 (95% CI, 0.61-0.71) before and after adjustment,
      respectively. LIMITATIONS: Limited capture of oral nutritional supplement intake
      outside the facility and potential residual confounding from unmeasured
      variables, such as dietary intake. CONCLUSIONS: Maintenance hemodialysis patients
      with albumin levels <=3.5 g/dL who received monitored intradialytic oral
      nutritional supplements showed survival significantly better than similar matched
      patient controls, with the as-treated analysis highlighting the potentially large
      effect of this strategy in clinical practice.

PMID- 22632808
TI  - Single-incision laparoscopy for colorectal resection: a systematic review and
      meta-analysis of more than a thousand procedures.
AB  - AIM: Single-incision laparoscopy for colorectal surgery is of growing importance.
      The experience of colorectal resection through single-incision laparoscopic
      surgery was assessed, including the patient outcomes. METHOD: A meta-analysis was
      performed of studies comparing single-incision laparoscopic with multiport
      laparoscopy. Endpoints included conversion to laparotomy, operation time,
      postoperative morbidity, length of skin incision and length of hospital stay. The
      MEDLINE database was searched and only comparative studies were included in the
      meta-analysis. Data were retrieved from full-text manuscripts. Meta-analysis was
      performed according to the Mantel-Haenszel method for random effects. RESULTS:
      From October 2008 to December 2011, 1026 colorectal resections including 921
      colonic and 105 rectal procedures using single-incision laparoscopic surgery were
      reported in 64 studies. Meta-analysis of the 15 comparative studies, including a
      total of 1075 procedures (494 single-incision and 581 multiport laparoscopies),
      showed no difference in conversion to open laparotomy [odds ratio (OR) 0.58
      (0.24, 1.38); P=0.22], morbidity [OR 0.84 (0.61, 1.15); P=0.27] or operation time
      [weighted mean difference (WMD) -0.27 (-6.50, 5.95); P=0.93], but a significantly
      shorter total skin incision [WMD -0.52 (-0.79, -0.25); P<0.001] and a
      significantly shorter postoperative length of stay [WMD -0.75 (-1.30, -0.20);
      P=0.008] after single-incision laparoscopic surgery compared with a multiport
      laparoscopic approach. CONCLUSION: Although only 15 nonrandomized comparative
      studies of varying methodology have been reported, this systematic review and
      meta-analysis of more than 1000 colorectal procedures suggest that single
      incision laparoscopic colorectal surgery is feasible and safe.

PMID- 22632809
TI  - The influence of staff training on the violence prevention and management climate
      in psychiatric inpatient units.
AB  - Violence prevention and management is an important part of inpatient psychiatric
      nursing and specific staff training is regarded essential. The training should be
      based on primary, secondary and tertiary prevention. In Stockholm, Sweden, the
      Bergen model is a staff-training programme that combines this preventive approach
      with the theoretical nursing framework of the City model that includes three
      staff factors: positive appreciation of patients, emotional regulation and
      effective structure. We evaluated this combination of the Bergen and City models
      on the violence prevention and management climate in psychiatric inpatient wards.
      A 13-item questionnaire was developed and distributed to patients and staff in 41
      wards before the staff was trained and subsequently to 19 of these wards after
      training. Data analyses included factor analysis, Fisher's exact test and Mann
      Whitney U-test. The result showed that the staff on trained wards had a more
      positive perception of four of the items and the patients of one item. These
      items reflected causes of patient aggression, ward rules, the staff's emotional
      regulation and early interventions. The findings suggest that a focus on three
      levels of prevention within a theoretical nursing framework may promote a more
      positive violence prevention and management climate on wards.

PMID- 22632810
TI  - Anatomy of the visual word form area: adjacent cortical circuits and long-range
      white matter connections.
AB  - Circuitry in ventral occipital-temporal cortex is essential for seeing words. We
      analyze the circuitry within a specific ventral-occipital region, the visual word
      form area (VWFA). The VWFA is immediately adjacent to the retinotopically
      organized VO-1 and VO-2 visual field maps and lies medial and inferior to visual
      field maps within motion selective human cortex. Three distinct white matter
      fascicles pass within close proximity to the VWFA: (1) the inferior longitudinal
      fasciculus, (2) the inferior frontal occipital fasciculus, and (3) the vertical
      occipital fasciculus. The vertical occipital fasciculus terminates in or adjacent
      to the functionally defined VWFA voxels in every individual. The vertical
      occipital fasciculus projects dorsally to language and reading related cortex.
      The combination of functional responses from cortex and anatomical measures in
      the white matter provides an overview of how the written word is encoded and
      communicated along the ventral occipital-temporal circuitry for seeing words.

PMID- 22632811
TI  - Charting the functional relevance of Broca's area for visual word recognition and
      picture naming in Dutch using fMRI-guided TMS.
AB  - Magnetoencephalography (MEG) has shown pseudohomophone priming effects at Broca's
      area (specifically pars opercularis of left inferior frontal gyrus and precentral
      gyrus; LIFGpo/PCG) within ~100ms of viewing a word. This is consistent with
      Broca's area involvement in fast phonological access during visual word
      recognition. Here we used online transcranial magnetic stimulation (TMS) to
      investigate whether LIFGpo/PCG is necessary for (not just correlated with) visual
      word recognition by ~100ms. Pulses were delivered to individually fMRI-defined
      LIFGpo/PCG in Dutch speakers 75-500ms after stimulus onset during reading and
      picture naming. Reading and picture naming reactions times were significantly
      slower following pulses at 225-300ms. Contrary to predictions, there was no
      disruption to reading for pulses before 225ms. This does not provide evidence in
      favour of a functional role for LIFGpo/PCG in reading before 225ms in this case,
      but does extend previous findings in picture stimuli to written Dutch words.

PMID- 22632812
TI  - Dual routes for verbal repetition: articulation-based and acoustic-phonetic codes
      for pseudoword and word repetition, respectively.
AB  - Speech production is inextricably linked to speech perception, yet they are
      usually investigated in isolation. In this study, we employed a verbal-repetition
      task to identify the neural substrates of speech processing with two ends active
      simultaneously using functional MRI. Subjects verbally repeated auditory stimuli
      containing an ambiguous vowel sound that could be perceived as either a word or a
      pseudoword depending on the interpretation of the vowel. We found verbal
      repetition commonly activated the audition-articulation interface bilaterally at
      Sylvian fissures and superior temporal sulci. Contrasting word-versus-pseudoword
      trials revealed neural activities unique to word repetition in the left posterior
      middle temporal areas and activities unique to pseudoword repetition in the left
      inferior frontal gyrus. These findings imply that the tasks are carried out using
      different speech codes: an articulation-based code of pseudowords and an acoustic
      phonetic code of words. It also supports the dual-stream model and imitative
      learning of vocabulary.

PMID- 22632813
TI  - Manipulating instructions strategically affects reliance on the ventral-lexical
      reading stream: converging evidence from neuroimaging and reaction time.
AB  - Neurobiology of reading research has yet to explore whether reliance on the
      ventral-lexical stream during word reading can be enhanced by the instructed
      reading strategy, or whether it is impervious to such strategies. We examined
      Instructions: name all vs. name words (based on spelling), Word Type: regular
      words vs. exception words, and Word Frequency (WF) in print (log10 HAL WF) in an
      experiment while measuring fMRI BOLD and overt naming reaction time (RT)
      simultaneously. Instructions to name words increased overall reliance on the
      ventral-lexical stream, as measured by visible BOLD activation and the WF effect
      on RT, with regular words showing the greatest effects as a function of this
      reading strategy. Furthermore, the pattern of joint effects of these variables on
      RT supports the notion of cascaded, not parallel, processing. These results can
      be accommodated by dual-stream cascaded models of reading, and present a
      challenge to single-mechanism parallel processing models.

PMID- 22632814
TI  - Fiber anatomy of dorsal and ventral language streams.
AB  - Recent advances in neuroimaging have led to new insights into the organization of
      language related networks. Increasing evidence supports the model of dorsal and
      ventral streams of information flow between language-related areas. Therefore, a
      review of the descriptions of language-related fiber anatomy in the human and
      monkey brain was performed. In addition, case studies of macroscopical fiber
      dissection and polarized light imaging (PLI) with special focus on the ventral
      stream were done. Several fiber structures can be identified to play a role in
      language, i.e. the arcuate fasciculus as a part of the superior longitudinal
      fasciculus, the middle longitudinal fasciculus, the inferior fronto-occipital
      fasciculus, and extreme and external capsules. Substantial differences between
      human and monkey fiber architecture have been identified. Despite inconsistencies
      based on different terminologies used, there can be no doubt that dorsal and
      ventral language streams have a clear correlation in the structure of white
      matter tracts. 

PMID- 22632815
TI  - Reading aloud in Persian: ERP evidence for an early locus of the masked onset
      priming effect.
AB  - The current study investigates reading aloud words in Persian, a language that
      does not mark all its vowels in the script. Behaviorally, a masked onset priming
      effect (MOPE) was revealed for transparent words, with faster speech onset
      latencies in the phoneme-matching condition (i.e. phonological prime and target
      onset overlap; e.g. [symbol: see text] /salpha?l/; 'year' [symbol: see text]
      /sot/; 'voice') than the phoneme-mismatching condition (e.g. [symbol: see text]
      /talpha?b/ 'swing' - [symbol: see text] /sot/; 'voice'). For opaque target words
      (e.g. [symbol: see text] /solh/; 'peace'), no such effect was found. However,
      event-related potentials (ERPs) did reveal an amplitude difference between the
      two prime conditions in the 80-160 ms time window for transparent as well as
      opaque words. Only for the former, this effect continued into the 300-480 ms time
      window. This finding constrains the time course of the MOPE and suggests the
      simultaneous activation of both the non-lexical grapheme-to-phoneme and the
      lexical route in the dual-route cascaded (DRC) model.

PMID- 22632816
TI  - Immunosuppression effects of bone marrow mesenchymal stem cells on renal
      interstitial injury in rats with unilateral ureteral obstruction.
AB  - We investigated the effects of intravenously administered bone marrow mesenchymal
      stem cells (BMSCs) on renal interstitial inflammation and fibrosis. In unilateral
      ureteral obstruction (UUO) rats, the CD4(+)CD25(+) regulatory T-cell (Treg) cell,
      macrophage population and some inflammation related cytokines were tested. In the
      BMSCs -treated rats, renal exhibited lower renal Masson scores, decreased
      macrophage infiltration and interferon gamma (IFNgamma) expression, and increased
      forkhead transcription factor (Foxp3) and interleukin-10 (IL-10) expression. No
      significant differences in the CD4(+)CD25(+) Treg population and renal
      transforming growth factor-beta1 (TGFbeta1) expression were observed between
      BMSCs-treated group and control group (p>0.05). In conclusion, BMSCs infusion
      leads to an anti-inflammation response in the early stage of UUO which may
      related to paracine mechanism.

PMID- 22632817
TI  - pH-Sensitive polymeric micelles for programmable drug and gene delivery.
AB  - Polymeric micelles (PMs) belong to supramolecular core-shell-type assemblies. PMs
      are from amphiphilic block copolymers with several tens of nanometers in
      diameter. An important criterion verifying the effectiveness of micellar drug
      carriers is the ability to control the location and time over which drug release
      occurs. The pH variations in the body are particularly important in the
      development of micellar carriers for treating diseases such as cancer and
      inflammation. pH-sensitive PMs have emerged as a fascinating class of nanoscopic
      drug carriers that can be elegantly applied for programmed drug and gene
      delivery. In this review, we provide an analysis of recent literature reports on
      these pH-sensitive PMs. Different approaches that have been taken to develop pH
      sensitive PMs are highlighted, including incorporating pH-sensitive building
      blocks such as poly(L-histidine) and poly(beta-amino ester), and acid degradable
      linkages such as hydrazones and acetals. The potential applications of pH
      sensitive PMs within the biomedical field are also summarized.

PMID- 22632818
TI  - Protein kinase G-I deficiency induces pulmonary hypertension through Rho A/Rho
      kinase activation.
AB  - Protein kinase G (PKG) plays an important role in the regulation of vascular
      smooth cell contractility and is a critical mediator of nitric oxide signaling,
      which regulates cardiovascular homeostasis. PKG-I-knockout (Prkg1(-/-)) mice
      exhibit impaired nitric oxide/cGMP-dependent vasorelaxation and systemic
      hypertension. However, it remains unknown whether PKG-I deficiency induces
      pulmonary hypertension. In this study, we characterized the hypertensive
      pulmonary phenotypes in Prkg1(-/-) mice and delineated the underlying molecular
      basis. We observed a significant increase in right ventricular systolic pressure
      in Prkg1(-/-) mice in the absence of systemic hypertension and left-sided heart
      dysfunction. In addition, we observed marked muscularization of distal pulmonary
      vessels in Prkg1(-/-) mice. Microangiography revealed impaired integrity of the
      pulmonary vasculature in Prkg1(-/-) mice. Mechanistically, PKG-I-mediated
      phosphorylation of Rho A Ser188 was markedly decreased, and the resultant Rho A
      activation was significantly increased in Prkg1(-/-) lung tissues, which resulted
      in Rho kinase activation. The i.t. administration of fasudil, a Rho kinase
      inhibitor, reversed the hypertensive pulmonary phenotype in Prkg1(-/-) mice.
      Taken together, these data show that PKG-I deficiency induces pulmonary
      hypertension through Rho A/Rho kinase activation-mediated vasoconstriction and
      pulmonary vascular remodeling.

PMID- 22632819
TI  - YAP promotes breast cell proliferation and survival partially through stabilizing
      the KLF5 transcription factor.
AB  - The Yes-associated protein (YAP), an oncoprotein in the Hippo tumor suppressor
      pathway, regulates tumorigenesis and has been found in a variety of tumors,
      including breast, ovarian, and hepatocellular cancers. Although YAP functions
      through its WW domains, the YAP WW domain-binding partners have not yet been
      completely determined. With this study, we demonstrate that YAP functions
      partially through its binding to KLF5, a transcription factor that promotes
      breast cell proliferation and survival. YAP interacted with the KLF5 PY motif
      through its WW domains, preventing the E3 ubiquitin ligase WWP1 from
      ubiquitinating KLF5. Overexpression of the wild-type YAP but not the WW domain
      mutated YAP up-regulated KLF5 protein levels and mRNA expression levels of KLF5
      downstream target genes, including FGFBP1 (alias FGF-BP) and ITGB2. In addition,
      knockdown of YAP decreased expression levels of KLF5, FGF-BP, and ITGB2.
      Depletion of either YAP or KLF5 decreased breast cell proliferation and survival
      in MCF10A and SW527 breast cell lines, and stable knockdown of either YAP or KLF5
      suppressed SW527 xenograft growth in mice. The YAP upstream kinase LATS1
      suppressed the KLF5-FGF-BP axis, as well as cell growth through YAP signaling.
      Both YAP and KLF5 are coexpressed in estrogen receptor ERalpha-negative breast
      cell lines. These findings suggest that KLF5 could be an important transcription
      factor partner for YAP and may contribute to the Hippo pathway.

PMID- 22632820
TI  - High rate EHR adoption in Korea and health IT rise in Asia.

PMID- 22632822
TI  - Hepatitis C transmission due to contamination of multidose medication vials:
      summary of an outbreak and a call to action.
AB  - In May 2001, The New York City Department of Health and Mental Hygiene was
      informed of a cluster of 4 patients treated at an outpatient gastroenterology
      center who developed acute hepatitis C virus infection. An investigation
      identified a total of 12 clinic-associated hepatitis C virus transmissions and
      the outbreak and was traced to unsafe handling of multidose anesthetic vials and
      possible re-use of contaminated needles. This report typifies the types of
      outbreaks that continue to occur despite safe injection guidelines.

PMID- 22632821
TI  - Development of a prototype continuity of care record with context-specific links
      to meet the information needs of case managers for persons living with HIV.
AB  - OBJECTIVES: (1) To develop a prototype Continuity of Care Record (CCR) with
      context-specific links to electronic HIV information resources; and (2) to assess
      case managers' perceptions regarding the usability of the prototype. METHODS: We
      integrated context-specific links to HIV case management information resources
      into a prototype CCR using the Infobutton Manager and Librarian Infobutton
      Tailoring Environment (LITE). Case managers (N=9) completed a think-aloud
      protocol and the Computer System Usability Questionnaire (CSUQ) to evaluate the
      usability of the prototype. Verbalizations from the think-aloud protocol were
      summarized using thematic analysis. CSUQ data were analyzed with descriptive
      statistics. RESULTS: Although participants expressed positive comments regarding
      the usability of the prototype, the think-aloud protocol also identified the need
      for improvement in resource labels and for additional resources. On a scale
      ranging from 1 (strongly agree) to 7 (strongly disagree), the average CSUQ
      overall satisfaction was 2.25 indicating that users (n=9) were generally
      satisfied with the system. Mean CSUQ factor scores were: System Usefulness
      (M=2.13), Information Quality (M=2.46), and Interface Quality (M=2.26).
      CONCLUSION: Our novel application of the Infobutton Manager and LITE in the
      context of case management for persons living with HIV in community-based
      settings resulted in a prototype CCR with infobuttons that met the majority of
      case managers' information needs and received relatively positive usability
      ratings. Findings from this study inform future integration of context-specific
      links into CCRs and electronic health records and support their use for meeting
      end-users information needs.

PMID- 22632823
TI  - Active training and surveillance: 2 good friends to reduce urinary
      catheterization rate.
AB  - BACKGROUND: Because catheter-associated urinary tract infections (CAUTI)
      represent the most frequent health care-associated infection (HAI), we
      implemented an educational intervention on urinary catheter use to reduce the
      CAUTI rate. METHODS: The intervention was focused on correct management of
      catheterized patients. To assess the participants' knowledge, pre- and post-tests
      were performed. An active CAUTI surveillance program took place in a 900-bed
      teaching hospital in central Italy before and after the educational intervention.
      CAUTI definition, catheterization rate, and CAUTI rate were expressed according
      to the Centers for Disease and Prevention/National Healthcare Safety Network
      definitions. The level of significance was set at P <= .05. RESULTS: Two hundred
      ninety-six health care workers attended the educational intervention; the
      analysis of the pre- and post-tests highlighted a statistically significant
      improvement (P < .05). Before the intervention, mean catheterization rate was
      18.5% (95% confidence interval [CI]:18.1-18.9); 46 cases of CAUTI were detected,
      with an incidence rate of 6.6/1,000 catheter-days (95% CI: 4.8-8.8). After the
      intervention, mean catheterization rate was 9.2% (95% CI: 8.9-9.5); 19 cases of
      CAUTI were detected, with an incidence rate of 5.8/1,000 catheter-days (95% CI:
      3.5-9.0). CONCLUSION: Through an active educational update and thanks to the
      implementation of a surveillance system, a successful reduction of
      catheterization rate was achieved. More efforts are needed to preserve this goal
      and to improve the CAUTI rate also.

PMID- 22632824
TI  - Periodic sterility assessment of materials stored for up to 6 months at
      continuous microbial contamination risk: laboratory study.
AB  - An investigation was conducted to test the hypothesis that the storage time of
      packaging sterility has no effect on contamination susceptibility even under
      deliberate bacterial exposure (Serratia marcescens). No growth of the test
      microorganisms was identified in the experimental group in any of the storage
      intervals (7, 14, 28, 90, and 180 days). Current recommendations/guidelines
      suggest that contamination of packaging occurs only because of events. This
      study, done in vitro, supports these recommendations.

PMID- 22632825
TI  - Assembly of synaptic laminae by axon guidance molecules.
AB  - A prominent feature of nervous systems is the organization of synapses into
      discrete layers, or laminae. Such laminae are essential for the spatial
      segregation of synaptic connections conveying different types of information. A
      prime example of this is the inner plexiform layer (IPL) of the vertebrate
      retina, which is subdivided into at least ten sublaminae. Another example gaining
      prominence is the layered neuropil of the zebrafish optic tectum. Three recent
      papers have shed light on the extracellular signals that control the precise
      stratification of pre- and postsynaptic neuronal processes in these two areas.
      The new studies implicate well-known axon guidance cues, including class 5 and 6
      semaphorins in the retina, as well as Slit in the optic tectum. Remarkably, the
      short-range action of Slit, which is required for neurite stratification, appears
      to be achieved by anchoring the secreted guidance factor to the basement membrane
      at the surface of the tectum.

PMID- 22632826
TI  - Usefulness of the Charlson co-morbidity index to predict outcomes in patients >60
      years old with aortic stenosis during 18 years of follow-up.
AB  - The present study assessed the effect of age and co-morbidity on the outcomes of
      mild, moderate, and severe aortic stenosis (AS) in patients aged >60 years during
      18 years of follow-up. The outcomes evaluated were hemodynamic progression, a
      composite cardiac mortality or aortic valve replacement (AVR) end point, and all
      cause mortality. Consecutive Department of Veterans Affairs patients (aged >60
      years) with AS were prospectively enrolled from 1988 to 1994 and followed until
      2008 (n = 239). The baseline demographic, co-morbidity, and echocardiographic
      parameters were recorded. At enrollment, the mean age was 74 +/- 6 years, and 78%
      were men. The annualized mean aortic valve gradient progression was 4 +/- 4, 6 +/
      5, and 10 +/- 8 mm Hg for mild, moderate, and severe AS, respectively (p
      <0.001). During a mean follow-up of 8 +/- 5 years, 206 deaths (52% cardiac) and
      91 AVRs were recorded. The AVR/cardiac mortality event rate at 1, 5, and 10 years
      was 2%, 26%, and 50% for mild AS, 13%, 63%, and 69% for moderate AS, and 66%,
      95%, and 95% for severe AS (p <0.001). During the study period, 132 patients
      developed severe AS. The survival rate at 1, 5, and 10 years was 60 +/- 7%, 14 +/
      5%, and 5 +/- 3% with conservative management and 98 +/- 2%, 82 +/- 4%, and 50
      +/- 5% after AVR, respectively (p <0.001). The independent predictors of all
      cause mortality were the age-adjusted Charlson co-morbidity index (hazard ratio
      1.24, p <0.001), AVR (hazard ratio 0.40, p <0.001), and grade of left ventricular
      dysfunction (hazard ratio 1.36, p = 0.01). In conclusion, the prognostic
      significance of AS is determined by the hemodynamic severity, left ventricular
      function, and the presence of symptoms, in the context of age and co-morbidities.
      The age-adjusted Charlson co-morbidity index provides crucial prognostic
      information to guide the surgical risk/benefit discussions for patients with
      severe AS.

PMID- 22632828
TI  - Transthoracic echocardiographic parameters in the estimation of pulmonary
      capillary wedge pressure in patients with present or previous heart failure.
AB  - Multiple echocardiographic criteria are routinely used for the estimation of left
      heart filling pressures. We assessed the predictive value of various
      echocardiographic parameters to estimate the left heart filling pressure and
      proposed a simplified approach for its evaluation. We collected the clinical,
      echocardiographic, and invasive hemodynamic data from 93 patients with heart
      failure who underwent right-sided heart catheterization and transthoracic
      echocardiography within a 24-hour period. Of these 93 patients, 57% had a left
      ventricular ejection fraction <50% and 69% had an elevated mean pulmonary
      capillary wedge pressure of >= 15 mm Hg. A mitral E/E' of >= 15 had a sensitivity
      of 55% but a specificity of 96%. A left atrial area of >= 20 cm(2) had a
      sensitivity of 66% and specificity of 89%. A deceleration time <140 ms had a
      sensitivity of 51% and specificity of 93% to predict a pulmonary capillary wedge
      pressure of >= 15 mm Hg. The combination of E/E' >= 15 +/- left atrial area of >=
      20 cm(2) +/- deceleration time <140 ms provided a sensitivity of 92% and
      specificity of 85%. On multivariate analysis, the combination of E/E' >= 15, left
      atrial area of >= 20 cm(2), and deceleration time <140 ms was the most
      significant predictor of a pulmonary capillary wedge pressure of >= 15 mm Hg
      (odds ratio 48, 95% confidence interval 10 to 289, p <0.001). In conclusion, this
      simplified approach using 3 echocardiographic parameters provides an accurate and
      a practical approach for the routine estimation of the elevated left heart
      filling pressure.

PMID- 22632827
TI  - Usefulness of hemoglobin A(1c) to predict outcome after cardiac resynchronization
      therapy in patients with diabetes mellitus and heart failure.
AB  - Patients with diabetes and heart failure (HF) have worse clinical outcomes
      compared to patients with HF without diabetes after cardiac resynchronization
      therapy (CRT). Patients with HF and diabetes represent a growing population at
      high risk for cardiovascular events and are increasingly treated with CRT.
      Although patients with diabetes and HF appear to benefit from CRT, their clinical
      outcomes are worse than those of patients without diabetes after CRT. The aim of
      this study was to identify clinical predictors that explain the differential
      hazard in patients with diabetes. We studied 442 patients (169 with diabetes)
      with systolic HF referred to the Massachusetts General Hospital CRT clinic from
      2003 to 2010 to identify predictors of outcomes after CRT in patients with HF and
      diabetes. Patients with diabetes were more likely to have ischemic causes of HF
      than those without diabetes, but there was no difference in the left ventricular
      ejection fraction or HF classification at implantation. Patients with diabetes
      had poorer event-free survival (death or HF hospitalization) compared to those
      without diabetes (log-rank p = 0.04). The presence of diabetes was the most
      important independent predictor of differential outcomes in the entire population
      (hazard ratio 1.65, 95% confidence interval 1.10 to 2.51). Patients with diabetes
      receiving insulin therapy had poorer survival, whereas those not receiving
      insulin therapy had similar survival to patients without diabetes. Patients with
      peri-implantation glycosylated hemoglobin >7% had worse outcomes, whereas
      patients with glycosylated hemoglobin <=7% had improved survival (hazard ratio
      0.36, 95% confidence interval 0.15 to 0.86) equivalent to that of patients
      without diabetes. In conclusion, although the presence of diabetes, independent
      of other variables, increases the hazard of worse outcomes after CRT, there is
      additional risk conferred by insulin use and suboptimal peri-implantation
      glycemic control.

PMID- 22632829
TI  - Outcomes of coronary revascularization (percutaneous or bypass) in patients with
      diabetes mellitus and multivessel coronary disease.
AB  - Clinical outcomes in patients with diabetes mellitus and multivessel disease
      (MVD) undergoing coronary revascularization have not been extensively evaluated,
      we sought to examine outcomes in a diabetic cohort of 195 consecutive patients
      with MVD characterized by SYNTAX scores (SSs) undergoing nonrandomized
      revascularization, 102 (52%) by percutaneous intervention (PCI) and 93 (48%) by
      coronary artery bypass grafting (CABG) at Liverpool Hospital (Sydney, Australia)
      from June 2006 to March 2010. Clinical outcomes were assessed at a median term of
      14 months. The overall median SS was 44, with significantly higher SSs in CABG-
      than PCI-treated patients (48 vs 39, p <0.0001). There was a similar incidence of
      all-cause death, nonfatal myocardial infarction and stroke in PCI- and CABG
      treated patients (6.1% vs 8.3%, p = 0.383; 12% vs 4.9%, p = 0.152; 3.1% vs 3.5%,
      p = 0.680 respectively). However, the rates of target vessel revascularization
      and major adverse coronary and cerebral event were significantly higher in PCI
      treated patients than in those undergoing CABG (20% vs 1.2%, p <0.0001; 29% vs
      15%, p = 0.034). Despite a much higher SS, patients who underwent PCI achieved
      comparable outcomes at 1 year to those with diabetes mellitus and a SS >= 33 as
      reported in the SYNTAX trial. In conclusion, in this single-center nonrandomized
      observational study, coronary revascularization by PCI is associated with
      increased major adverse coronary and cerebral events at 1-year follow-up,
      predominantly driven by a high rate of target vessel revascularization. Thus,
      CABG should remain the revascularization procedure of choice for diabetic
      patients with MVD and high SSs.

PMID- 22632830
TI  - Outcomes of childhood pulmonary arterial hypertension in BMPR2 and ALK1 mutation
      carriers.
AB  - Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene and the
      activin receptor-like kinase 1 (ALK1) gene have been reported in heritable
      pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial
      hypertension (IPAH). However, the relation between clinical characteristics and
      each gene mutation in IPAH and HPAH is still unclear, especially in childhood.
      The aim of this study was to determine, in a retrospective study, the influence
      and clinical outcomes of gene mutations in childhood IPAH and HPAH. Fifty-four
      patients with IPAH or HPAH whose onset of disease was at <16 years of age were
      included. Functional characteristics, hemodynamic parameters, and clinical
      outcomes were compared in BMPR2 and ALK1 mutation carriers and noncarriers.
      Overall 5-year survival for all patients was 76%. Eighteen BMPR2 mutation
      carriers and 7 ALK1 mutation carriers were detected in the 54 patients with
      childhood IPAH or HPAH. Five-year survival was lower in BMPR2 mutation carriers
      than mutation noncarriers (55% vs 90%, hazard ratio 12.54, p = 0.0003). ALK1
      mutation carriers also had a tendency to have worse outcome than mutation
      noncarriers (5-year survival rate 64%, hazard ratio 5.14, p = 0.1205). In
      conclusion, patients with childhood IPAH or HPAH with BMPR2 mutation have the
      poorest clinical outcomes. ALK1 mutation carriers tended to have worse outcomes
      than mutation noncarriers. It is important to consider aggressive treatment for
      BMPR2 or ALK1 mutation carriers.

PMID- 22632831
TI  - Structural and functional similarity between the Vgll1-TEAD and the YAP-TEAD
      complexes.
AB  - The structure of the complex between the transcription cofactor Vgll1 and the
      transcription factor TEAD4, the mammalian equivalent of the Drosophila Vestigial
      and Scalloped, respectively, is determined in this study. Remarkably, Vgll1
      interacts with TEAD in a manner similar to the transcription coactivators, as
      well as oncogenes YAP and TAZ, despite having a varied primary sequence. Vgll1
      TEAD complex upregulates the expression of IGFBP-5, a proliferation-promoting
      gene, and facilitates anchorage-independent cell proliferation. The YAP/TAZ-TEAD
      complex also upregulates several other proliferation-promoting genes and also
      promotes anchorage-independent cell proliferation. Given its structural and
      functional similarity to YAP/TAZ, Vgll1 has the potential to promote cancer
      progression.

PMID- 22632832
TI  - Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin
      ligase.
AB  - The E3 ligases recruit substrate proteins for targeted ubiquitylation. Recent
      insights into the mechanisms of ubiquitylation demonstrate that E3 ligases can
      possess active regulatory properties beyond those of a simple assembly scaffold.
      Here, we describe the dimeric structure of the E3 ligase adaptor protein SPOP
      (speckle-type POZ protein) in complex with the N-terminal domain of Cul3 at 2.4 A
      resolution. We find that SPOP forms large oligomers that can form heteromeric
      species with the closely related paralog SPOPL. In combination, SPOP and SPOPL
      (SPOP-like) form a molecular rheostat that can fine-tune E3 ubiquitin ligase
      activity by affecting the oligomeric state of the E3 complex. We propose that
      adaptor protein self-assembly provides a graded level of regulation of the
      SPOP/Cul3 E3 ligase toward its multiple protein substrates.

PMID- 22632833
TI  - Increasing sequence diversity with flexible backbone protein design: the complete
      redesign of a protein hydrophobic core.
AB  - Protein design tests our understanding of protein stability and structure.
      Successful design methods should allow the exploration of sequence space not
      found in nature. However, when redesigning naturally occurring protein
      structures, most fixed backbone design algorithms return amino acid sequences
      that share strong sequence identity with wild-type sequences, especially in the
      protein core. This behavior places a restriction on functional space that can be
      explored and is not consistent with observations from nature, where sequences of
      low identity have similar structures. Here, we allow backbone flexibility during
      design to mutate every position in the core (38 residues) of a four-helix bundle
      protein. Only small perturbations to the backbone, 1-2 A, were needed to entirely
      mutate the core. The redesigned protein, DRNN, is exceptionally stable (melting
      point >140 degrees C). An NMR and X-ray crystal structure show that the side
      chains and backbone were accurately modeled (all-atom RMSD = 1.3 A).

PMID- 22632834
TI  - The human nuclear pore complex as revealed by cryo-electron tomography.
AB  - Nuclear pore complexes (NPCs) are the sole passage through the nuclear envelope,
      connecting the cytoplasm to the nucleoplasm. These gigantic molecular machines,
      over 100 MDa in molecular weight, allow free diffusion of small molecules and
      ions while mediating selective energy-dependent nucleocytoplasmic transport of
      large macromolecules. Here, we applied cryo-electron tomography to human
      fibroblast cells, reconstructing their nuclear envelopes without applying any
      purification steps. From these reconstructions, we extracted subtomograms
      containing individual NPCs and utilized in silico subtomogram averaging
      procedures to determine the structure of the mammalian pore complex at a
      resolution of ~6.6 nm. Beyond revealing the canonical features of the human NPC,
      our analysis identified inner lateral channels and fusing bridge-like structures,
      suggesting alternative routes of peripheral nuclear passage. Finally, we
      concluded from our structural analysis that the human NPC is structurally
      distinct from that of lower eukaryotes in terms of dimension and organization but
      resembles its amphibian (frog) counterpart.

PMID- 22632835
TI  - Structural reorganization triggered by charging of Lys residues in the
      hydrophobic interior of a protein.
AB  - Structural consequences of ionization of residues buried in the hydrophobic
      interior of proteins were examined systematically in 25 proteins with internal
      Lys residues. Crystal structures showed that the ionizable groups are buried. NMR
      spectroscopy showed that in 2 of 25 cases studied, the ionization of an internal
      Lys unfolded the protein globally. In five cases, the internal charge triggered
      localized changes in structure and dynamics, and in three cases, it promoted
      partial or local unfolding. Remarkably, in 15 proteins, the ionization of the
      internal Lys had no detectable structural consequences. Highly stable proteins
      appear to be inherently capable of withstanding the presence of charge in their
      hydrophobic interior, without the need for specialized structural adaptations.
      The extent of structural reorganization paralleled loosely with global
      thermodynamic stability, suggesting that structure-based pK(a) calculations for
      buried residues could be improved by calculation of thermodynamic stability and
      by enhanced conformational sampling.

PMID- 22632836
TI  - [Imaging findings in neurocysticercosis].
AB  - Neurocysticercosis, caused by the larvae of Taenia solium, is the parasitic
      infection that most commonly involves the central nervous system in humans.
      Neurocysticercosis is endemic in practically all developing countries, and owing
      to globalization and immigration it is becoming more common in developed
      countries like those in western Europe. The most common clinical manifestations
      are epilepsy, focal neurologic signs, and intracranial hypertension. The imaging
      findings depend on the larval stage of Taenia solium, on the number and location
      of the parasites (parenchymal, subarachnoid, or intraventricular), as well as on
      the host's immune response (edema, gliosis, arachnoiditis) and on the development
      of secondary lesions (arteritis, infarcts, or hydrocephalus). The diagnosis of
      this parasitosis must be established on the basis of the clinical and
      radiological findings, especially in the appropriate epidemiological context,
      with the help of serological tests.

PMID- 22632837
TI  - Deep venous thrombosis and pulmonary embolism after surgical treatment of ankle
      fractures: a case report and review of literature.
AB  - Deep vein thrombosis and pulmonary embolism are major complications that can
      occur after ankle injuries. We present the case of a patient with an ankle
      fracture who developed deep vein thrombosis and massive pulmonary embolism after
      surgical treatment of the ankle fracture. A review of the published data on this
      topic is presented. The treating physician should assess patients with ankle
      fracture for their risk of developing a venous thromboembolic event on an
      individual basis and provide thromboprophylaxis for those with an increased risk
      of developing such complications.

PMID- 22632838
TI  - Muller-Weiss disease of the tarsal navicular: an idiopathic case.
AB  - Muller-Weiss disease of the tarsal navicular is a rare condition, the etiology of
      which remains unclear. We present the case of a 28-year-old woman with classic
      radiographic findings consistent with Muller-Weiss disease. The patient was
      successfully treated with a talonavicular-cuneiform arthrodesis of her right
      foot. Radiographs at 6 months postoperatively demonstrated a successful medial
      arch fusion. At 38 months follow-up, the patient was asymptomatic. The American
      Academy of Orthopaedic Surgeons ankle hindfoot score was 97, compared with a
      preoperative score of 32.

PMID- 22632839
TI  - Treatment of hammertoe deformity using a one-piece intramedullary device: a case
      series.
AB  - Hammertoes are common deformities that are often surgically treated using
      arthrodesis or arthroplasty of the proximal interphalangeal joint with
      percutaneous, temporary Kirschner wire fixation. However, percutaneous Kirschner
      wire fixation is associated with potential complications, including wire
      migration, breakage, and pin tract infection. Furthermore, the complications of
      pseudoarthrosis and nonunion are seen using this technique owing to a lack of
      rotational control of the Kirschner wire. Another drawback of this implant is the
      need for wire removal and the associated patient anxiety with this in-office
      procedure. In the present series of 7 toes in 3 patients, we describe an
      alternative method of hammertoe fixation using a permanently implanted, 1-piece
      intramedullary device used to stabilize the proximal interphalangeal interface.
      The potential advantages of this prosthesis include elimination of wire migration
      and breakage, enhanced control and stability of the digit, elimination of
      potential pin tract infection, and decreased patient anxiety since hardware
      removal is not required. The patients were followed up for approximately 1 year
      after the surgery, and no intraoperative or postoperative complications were
      observed. The implant maintained proper clinical and radiographic alignment
      throughout the observation period, without implant failure or breakage. All
      patients were satisfied with the cosmetic appearance of their surgically
      corrected toes and were able to perform all activities of daily living without
      the use of assistive devices. Also, their postoperative pain and function were
      acceptable. The implant used in the patients described in the present report
      appears to be a viable alternative for the treatment of hammertoe.

PMID- 22632840
TI  - Intramedullary foot fixation for midfoot Charcot neuroarthropathy.
AB  - Midfoot Charcot collapse commonly occurs through the tarsometatarsal and/or
      midtarsal joints, which creates the characteristic "rocker bottom" deformity.
      Intramedullary metatarsal fixation spanning the tarsus into the talus and/or
      calcaneus is a recently developed method for addressing unstable midfoot Charcot
      deformity. The intramedullary foot fixation technique has various advantages when
      addressing midfoot Charcot deformity in the neuropathic patient. These advantages
      include anatomical realignment, minimally invasive fixation technique, formal
      multiple joint fusion, adjacent joint fixation beyond the level of Charcot
      collapse, rigid interosseus fixation, and preservation of foot length. The goals
      of the intramedullary foot fixation procedure are to create a stable,
      plantigrade, and ulcer-free foot, which allows the patient to ambulate with
      custom-molded orthotics and shoes.

PMID- 22632841
TI  - An irreducible ankle fracture dislocation: the Bosworth injury.
AB  - Irreducible fracture dislocations of the ankle are rare and represent true
      orthopedic emergencies. We present a case of a fracture dislocation that was
      irreducible owing to a fixed dislocation of the proximal fibular fragment
      posterior to the lateral ridge of the tibia. This particular type of injury,
      known as a Bosworth fracture dislocation, was not appreciated on the initial
      radiographs taken in the emergency room but was identified at urgent surgical
      management. The trauma mechanism, radiographs, treatment, and relevant published
      data are discussed in the present report.

PMID- 22632842
TI  - Fixation of the Lapidus arthrodesis with a plantar interfragmentary screw and
      medial low profile locking plate.
AB  - The Lapidus arthrodesis can be used to correct pathology within the forefoot or
      midfoot, and severe hallux valgus deformities as well as hypermobility of the
      medial column may be amenable to correction with this procedure. Many different
      skeletal fixation methods have been described for this procedure, and one form
      that appears to provide enough construct stability to allow patients to bear
      weight early in the postoperative period is described herein. This construct
      consists of an interfragmental compression screw oriented from the plantar aspect
      of the first metatarsal to the superior aspect of the medial cuneiform, with
      medial locking plate augmentation.

PMID- 22632843
TI  - Atraumatic compartment syndrome of the foot in a 15-year-old female.
AB  - Compartment syndrome is a surgical emergency that usually occurs as a sequel to
      high-energy trauma. We report an uncommon presentation of atraumatic compartment
      syndrome of the right foot involving the abductor hallucis muscle. A 15-year-old
      female presented with pain and mild swelling of the right foot after taking part
      in a school sports activity. Compartment syndrome was diagnosed, >2 months of
      conservative treatment failed to improve her symptoms, and surgical release and
      debridement were performed. Our clinical experience demonstrates that compartment
      syndrome of the foot may occur after mild sports activity in physically inactive
      children.

PMID- 22632844
TI  - Are extrinsic black stains of teeth iron-saturated bovine lactoferrin and a sign
      of iron deficient anemia or iron overload?
AB  - Extrinsic black stains on teeth are shown to have a relation with a low incidence
      of caries and are made of a ferric compound. Whole composition and why those
      stains are formed are not fully understood. Studies have shown low incidence of
      caries in individuals eating cheese. Lactoferrin is the major iron-binding
      protein, constituent of milk, stays almost intact during cheese making and has
      antibacterial activity against dental cavity-inducing Streptococcus mutans.
      Lactoferrin has a high affinity for iron and whenever it is present it will bind
      iron and release it only in values of pH<4. In a small survey that I made in
      dental practice, patients (patients did not report taking any medication; had no
      frequent gingival bleeding) that had extrinsic black stains on teeth eat >50 g of
      cheese per day and a good number of them, in addition to cheese, drink one cup of
      milk per day. Cheese stays much longer in contact with tooth surface than does'
      milk and bovine lactoferrin has four glycan chains that may contribute to a
      better adherence. Extrinsic black stains are made of a ferric compound, and
      people that eat good amounts of cheese (where lactoferrin plays a central role)
      show to have black stains. Iron must be in sufficient amounts in saliva so that
      lactoferrin can bind it and as a result making the black stains appear. In iron
      deficient anemia and in iron overload the concentration of iron present in saliva
      is much higher than in individuals with no anemia. In conclusion, extrinsic black
      stains of teeth may be iron-saturated bovine lactoferrin and a sign of iron
      deficient anemia or iron overload if no iron supplements are taken or individuals
      have no frequent gingival bleeding.

PMID- 22632845
TI  - Could treatment of iron deficiency both improve ADHD and reduce cardiovascular
      risk during treatment with ADHD drugs?
AB  - Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common
      childhood-onset neuropsychiatric conditions. Despite extensive research, the
      etiopathophysiological factors underlying ADHD are not completely understood. It
      has been suggested that iron deficiency may contribute to ADHD symptoms severity.
      Whereas evidence from studies based on serum ferritin measures, a marker of
      peripheral iron status, is somewhat mixed, preliminary recent evidence suggests a
      deficiency of brain iron in individuals with ADHD. Therefore, it has been
      proposed that either a deficiency of peripheral iron or a dysfunction of the
      blood-brain barrier, in the presence of normal peripheral iron levels, may
      contribute to low brain iron levels, which, in turn, would increase the risk for
      ADHD symptoms in a subgroup of individuals with this disorder. It has also been
      found that individuals with ADHD may be at increased risk of severe
      cardiovascular events during treatment with ADHD drugs, although the extent to
      which this occurs in ADHD patients compared to non-ADHD individuals is still
      matter of investigation. Since iron depletion has been recently reported as a
      risk factor for adverse prognosis in heart failure, iron deficiency might
      contribute both to ADHD symptoms severity before treatment and to increased risk
      of severe cardiovascular events during treatment with ADHD drugs in a selected
      subgroup of patients. Therefore, we hypothesize that the effective treatment of
      iron deficiency might lead both to improvement of ADHD symptoms severity and to a
      decrease of the risk of cardiovascular events during treatment with ADHD drugs.
      If empirical studies confirm this hypothesis, the clinician would be advised to
      systematically check iron status and effectively treat iron deficiency before
      starting a pharmacological treatment with ADHD drugs.

PMID- 22632846
TI  - Listening to the rural health workers in Papua New Guinea - the social factors
      that influence their motivation to work.
AB  - Despite rural health services being situated and integrated within communities in
      which people work and live, the complex interaction of the social environment on
      health worker motivation and performance in Low Middle Income Countries has been
      neglected in research. In this article we investigate how social factors impact
      on health worker motivation and performance in rural health services in Papua New
      Guinea (PNG). Face-to-face in-depth interviews were conducted with 33 health
      workers from three provinces (Central, Madang, and Milne Bay) in PNG between
      August and November 2009. They included health extension officers, community
      health workers and nursing officers, some of whom were in charge of the health
      centres. The health centres were a selection across church based, government and
      private enterprise health facilities. Qualitative analysis identified the key
      social factors impacting on health worker motivation and performance to be the
      local community context, gender roles and family related issues, safety and
      security and health beliefs and attitudes of patients and community members. Our
      study identified the importance of strong supportive communities on health worker
      motivation. These findings have implications for developing sustainable
      strategies for motivation and performance enhancement of rural health workers in
      resource poor settings.

PMID- 22632847
TI  - Unmet needs among disabled elderly Malaysians.
AB  - Unmet need as a significant factor affecting quality of life in later life has
      recently received considerable attention in gerontological research. The main aim
      of this study was to identify the prevalence, predicting factors, and negative
      consequence of unmet need among older Malaysians. The findings may be useful to
      reduce unmet need and the burden of its adverse consequence. The sample for this
      study consists of 400 functionally disabled elderly people aged 60 and over was
      obtained from a large national survey. Unmet need was operationally defined based
      on Manton's (1989) criteria. The findings from the present study showed about
      18.0% of functionally disabled older Malaysians suffer from unmet need. Logistic
      regression revealed that gender (being male) and chronic health conditions are
      statistically associated with increased odds of unmet need after adjusting for
      other possible risk factors. Further results indicated that unmet need
      statistically increases odds of fall as a negative consequence of unmet need. The
      high prevalence rates of unmet need among disabled elderly men and chronically
      ill older persons suggest that policy makers should pay more attention to this
      vulnerable group to achieve good quality of life. The implications and
      limitations of the present study are discussed.

PMID- 22632848
TI  - Neoadjuvant chemoradiotherapy and multivisceral resection for primary locally
      advanced adherent colon cancer: a single institution experience.
AB  - BACKGROUND: Although there is an extensive body of literature on the role of
      neoadjuvant chemoradiotherapy (CRT) in the management of rectal cancer, its role
      in primary locally advanced adherent colon cancer (LAACC) is unclear. OBJECTIVE:
      To analyzed the outcomes of neoadjuvant CRT and multivisceral resection in the
      management of LAACC patietns. METHODS: We retrospectively reviewed our
      institutional Colorectal Carcinoma Database for 33 patients with potentially
      resectable, non-metastatic primary LAACC who received neoadjuvant CRT followed by
      multivisceral resection. CRT consisted of external beam radiation (45-50 Gy in 25
      daily fractions) and concurrent 5-FU infusion (225 mg/m(2)/day). RESULTS: There
      were 21 males and 12 females. Median age was 64 (31-83) and median follow-up was
      36 months. All patients had microscopically clear resection margins (R0).
      Complete pathologic response was documented in 1 patient (3%) and 66% had ypT4b
      disease. Post-operative complications were observed in 36% of patients with no 30
      day mortality. The 3-year overall survival and 3-year disease-free survival were
      85.9% and 73.7% respectively. Two patients developed a local recurrence.
      CONCLUSIONS: Neoadjuvant CRT and en-bloc multivisceral resection may result in
      high rates of R0 resection and excellent local control with acceptable morbidity
      and mortality in selected patients with LAACC.

PMID- 22632849
TI  - Resection hip arthroplasty as a feasible surgical procedure for periacetabular
      tumors of the pelvis.
AB  - AIMS: Surgical treatment of periacetabular tumors remains one of the most
      challenging problems in musculoskeletal oncology. The purpose of this study was
      to review the clinical and functional outcomes of resection hip arthroplasty and
      analyze its feasibility. METHODS: This study assesses twenty-seven patients with
      periacetabular tumors treated by resection hip arthroplasty between 1999 and
      2010. The tumors were excised with wide margins and the residual intact femoral
      head placed underneath the resected ilium. Clinical, functional and oncological
      outcomes as well as complications were carefully evaluated. RESULTS: The average
      follow-up time was 55 months (range, 3-118) and the mean surgical time 170 min
      (range, 120-350) with an average blood loss 1200 ml (range, 600-2200). Six
      patients died in 6-33 months postoperatively; no other local recurrences or
      deaths occurred. The 1-year, 5-year, and 10-year disease-free survival rates were
      96.3%, 77.8% and 77.8% respectively. The mean limb-length discrepancy was 5 cm
      (range, 2-7.5) and all patients required custom-made shoes with their heels
      heightened by 2-5 cm. At the last follow-up, the mean functional score was 75.6%.
      Twenty patients recovered normal ambulation function with custom-made shoes and
      seven had to walk with crutches. Wound healing problems were observed in nine
      patients and deep or superficial infection in none. CONCLUSIONS: Resection hip
      arthroplasty is recommended as a feasible surgical protocol for periacetabular
      tumors because it has few complications, good functional results, short surgical
      time and little blood loss.

PMID- 22632850
TI  - Whether to break confidentiality: an ethical dilemma.

PMID- 22632851
TI  - Customer service: the nursing bundle.

PMID- 22632852
TI  - Effectiveness of acupuncture and bee venom acupuncture in idiopathic Parkinson's
      disease.
AB  - This study aimed to explore the effectiveness of both acupuncture and bee venom
      acupuncture as adjuvant therapies for idiopathic Parkinson's disease. We
      recruited 43 adults with idiopathic Parkinson's disease who had been on a stable
      dose of antiparkinsonian medication for at least 1 month. They were randomly
      assigned to 1 of 3 groups: acupuncture, bee venom acupuncture, or control. All
      participants were assessed using the Unified Parkinson's Disease Rating Scale,
      the Parkinson's Disease Quality of Life Questionnaire, the Beck Depression
      Inventory, the Berg Balance Scale, and the time and number of steps required to
      walk 30 m. Treatment groups underwent stimulation of 10 acupuncture points using
      acupuncture or bee venom acupuncture twice a week for 8 weeks. The initial
      assessment was repeated at the completion of treatment. The control group did not
      receive any treatment. Participants in the bee venom acupuncture group showed
      significant improvement on the Unified Parkinson's Disease Rating Scale (total
      score, as well as parts II and III individually), the Berg Balance Scale, and the
      30 m walking time. When compared to the control group, the bee venom acupuncture
      group experienced significantly greater improvement on the Unified Parkinson's
      Disease Rating Scale. In the acupuncture group, the Unified Parkinson's Disease
      Rating Scale (part III and total scores) and the Beck Depression Inventory showed
      significant improvement. The control group showed no significant changes in any
      outcome after 8 weeks. In this pilot study, both acupuncture and bee venom
      acupuncture showed promising results as adjuvant therapies for Parkinson's
      disease.

PMID- 22632853
TI  - Long-term tremor control with bilateral Vim-DBS in vanishing white matter
      disease.

PMID- 22632854
TI  - Serum 25-hydroxyvitamin D predicts severity and prognosis in stroke patients.
AB  - BACKGROUND AND PURPOSE: We aimed to evaluate the association between 25
      hydroxyvitamin D (25(OH)D) levels and both clinical severity at admission and
      outcome at discharge in stroke patients. METHODS: From February 2010 to December
      2010, consecutive stroke patients admitted to the Department of Neurology of
      Dijon, France, were identified. Clinical information was collected. Serum
      concentration of 25(OH)D was measured at baseline. Stroke severity was assessed
      at admission using the NIHSS score. Functional impairment was evaluated at
      discharge using the modified Rankin scale (m-Rankin). Multivariate analyses were
      performed using logistic regression models. RESULTS: Of the 386 recorded
      patients, serum 25(OH)D levels were obtained in 382 (median value = 35.1 nM; IQR
      = 21-57.8). At admission, 208 patients had a NIHSS <=5, with a higher mean
      25(OH)D level than that observed in patients with moderate-to-high severity (45.9
      vs. 38.6 nM, P < 0.001). In multivariate analyses, a 25(OH)D level in the lowest
      tertile (<25.7 nM) was a predictor of a NIHSS >=6 (OR = 1.67; 95% CI = 1.05-2.68;
      P = 0.03). The mean 25(OH)D level was lower in patients with moderate-to-severe
      handicap at discharge (m-Rankin 3-6) than in patients with no or mild handicap
      (35.0 vs. 47.5 nM, P < 0.001). In multivariate analyses, the lowest tertile of
      25(OH)D level (<25.7 nM) was associated with a higher risk of moderate-to-severe
      handicap (OR = 2.06; 95% CI = 1.06-3.94; P = 0.03). CONCLUSION: A low serum
      25(OH)D level is a predictor of both severity at admission and poor early
      functional outcome in stroke patients. The underlying mechanisms of these
      associations remain to be investigated.

PMID- 22632855
TI  - Diagnostic accuracy in child sexual abuse medical evaluation: role of experience,
      training, and expert case review.
AB  - OBJECTIVES: (1) The purpose of this study was to assess the ability of clinicians
      who examine children for suspected sexual abuse to recognize and interpret normal
      and abnormal ano-genital findings in magnified photographs using an online survey
      format. (2) Determine which factors in education, clinical practice, and case
      review correlate with correct responses to the survey questions. METHODS: Between
      July and December 2007, medical professionals participated in a web-based survey.
      Participants answered questions regarding their professional background,
      education, clinical experience, and participation in case review. After viewing
      photographs and clinical information from 20 cases, participants answered 41
      questions regarding diagnosis and medical knowledge. Answers chosen by an expert
      panel were used as the correct answers for the survey. RESULTS: The mean number
      of correct answers among the 141 first-time survey respondents was 31.6 (SD 5.9,
      range 15-41). Child Abuse Pediatricians (CAP) had mean total scores which were
      significantly higher than Pediatricians (Ped) (34.8 vs. 30.1, p<0.05) and Sexual
      Assault Nurse Examiners (SANE) (34.8 vs. 29.3, p<0.05). The mean total scores for
      Ped, SANE, and Advanced Practice Nurses (APN) who examine fewer than 5 children
      monthly for possible CSA were all below 30. Total score was directly correlated
      with the number of examinations performed monthly (p=0.003). In multivariable
      regression analysis, higher total score was associated with self-identification
      as a CAP, reading The Quarterly Update newsletter (p<0.0001), and with quarterly
      or more frequent expert case reviews using photo-documentation (p=0.0008).
      CONCLUSIONS: Child Abuse Pediatricians, examiners who perform many CSA
      examinations on a regular basis, examiners who regularly review cases with an
      expert, and examiners who keep up to date with current research have higher total
      scores in this survey, suggesting greater knowledge and competence in
      interpreting medical and laboratory findings in children with CSA. Review of
      cases with an expert in CSA medical evaluation and staying up to date with the
      CSA literature are encouraged for non-specialist clinicians who examine fewer
      than 5 children monthly for suspected sexual abuse.

PMID- 22632856
TI  - The growth hormone secretagogue receptor (Ghs-R).
AB  - The growth hormone secretagogue receptor (GHS-R) is a component of the ghrelin
      signaling pathway and is involved in mediating the pleiotropic effects of
      ghrelin. Two isoforms have been identified, but only GHS-R1a binds with acyl
      ghrelin and transduces its message. However, the inactive variant of GHS-R, GHS
      R1b, appears to play a critical role in modulating the activity of GHS-R1a by
      forming heterodimeric complexes which attenuates trafficking of the active
      variant to the cell surface. The molecular mechanisms of signal transduction are
      complex and are specific of the tissues where GHS-R1a is expressed. The potent
      induction of GH secretion and the stimulation of appetite are the most
      intensively studied functions of GHS-R1a. However, the tissue distribution of GHS
      R1a extends beyond the pituitary and the hypothalamus, and reflects the different
      biological functions of the ghrelin/GHS-R system. GHS-R1a is also expressed in
      other brain areas, in the pancreas, adipose tissue, immune cells and
      cardiovascular system, and modulates learning and memory, glucose and lipid
      metabolism, inflammatory response and cardiac performance. The pleiotropic
      effects of the ghrelin/GHS-R system suggest their exploitation to prevent and
      treat a number of clinical conditions. Among many other syndromes and diseases,
      cancer cachexia, aging related cognitive decline, obesity and diabetes may
      significantly benefit from the use of GHS-R1a agonists or antagonists.

PMID- 22632857
TI  - Ghrelin and motilin in the gastrointestinal system.
AB  - Human ghrelin and human motilin, belonging to the ghrelin/motilin-related peptide
      family, share 36% amino acid sequence identity, while the human ghrelin receptor
      exhibits a remarkable 50% overall identity with the human motilin receptor. In
      addition to their structural resemblance, ghrelin and motilin are the only two
      mammalian hormones known to decrease in the postprandial period. Ghrelin and
      motilin participate in initiating the migrating motor complex in the stomach, and
      stimulate gastrointestinal motility, accelerate gastric emptying, and induce
      "gastric hunger". In addition to modulating the release of growth hormone and gut
      motility, ghrelin plays a crucial role in the secretion and protection of the
      stomach and colon. Ghrelin mimetics and motilin agonists are currently being
      developed to reverse gastrointestinal hypomotility disorders. With additional
      appetite-enhancing, adiposity-promoting, and anti-inflammatory effects, ghrelin
      and rikkunshito (a traditional Japanese herb enhancing acyl ghrelin signaling)
      are superior to motilin in the treatment of cancer-related anorexia and cachexia,
      post-chemotherapy symptoms, rheumatological diseases, age-related frailty, as
      well as post-operative, septic, and post-burn gut ileus.

PMID- 22632858
TI  - The role of NPY and ghrelin in anorexia nervosa.
AB  - Complex mechanisms have evolved that control feeding and energy homeostasis in
      mammals. Centrally, particularly in the hypothalamus, numerous neurotransmitters
      have been identified that regulate appetite and energy homeostasis. On the other
      hand, hormones released from the gut signal states of hunger and satiety to the
      brain. From the large number of players involved in this interplay, peptides from
      the neuropeptide Y (NPY) family are unique, with the predominantly neuronally
      expressed NPY being one of the most strongly stimulating agents for food intake
      while its two other closely related family members peptide YY (PYY) and
      pancreatic polypeptide (PP) released from the gut induce satiety. Another major
      player in this circuitry is ghrelin, which is released from the stomach and is
      the only known hormone that signals hunger to the brain. It is doing this by
      stimulating hypothalamic NPY production and release, subsequently leading to
      increased appetite and feeding behaviour. Deregulation of these processes can
      lead to either the development of obesity or the other extreme, anorexia. The aim
      of this review is to summarize the recent literature on NPY and ghrelin and its
      involvement in anorexia nervosa.

PMID- 22632860
TI  - Clinical application of ghrelin.
AB  - Ghrelin as a human natural hormone is involved in fundamental regulatory
      processes of eating and energy balance. Ghrelin signals the nutrient availability
      from the gastrointestinal tract to the central nervous system, up-regulates food
      intake and lowers energy expenditure mainly through hypothalamic mediators acting
      both centrally and peripherally including the gastrointestinal tract (motility,
      epithelium), promotes both neuro-endocrine and inflammatory signals to increase
      skeletal muscle growth and decrease protein breakdown, and increases lipolysis
      while body fat utilization is reduced. Ghrelin does more to exert its probably
      sentinel role around "human energy": it influences through mainly extra
      hypothalamic actions the hedonic and incentive value of food, mood and anxiety,
      sleep-wake regulation, learning and memory, and neurogenesis. Recently numerous
      ghrelin gene-derived peptides were discovered, demonstrating the complexity
      within the ghrelin/ghrelin receptor axis. For clinical applications, not only the
      natural ghrelin and its slice variants, but also several modified or artificial
      molecules acting at ghrelin-associated receptors were and are developed. Current
      clinical applications are limited to clinical studies, focusing mainly on
      cachexia in chronic heart failure, COPD, cancer, endstage- renal-disease or
      cystic fibrosis, but also on frailty in elderly, gastrointestinal motility (e.g.,
      gastroparesis, functional dyspepsia, postoperative ileus), after curative
      gastrectomy, anorexia nervosa, growth hormone deficient patients, alcohol
      craving, sleep-wake regulation (e.g. major depression), or sympathetic nervous
      activity in obesity. The results of completed, preliminary studies support the
      clinical potential of ghrelin, ghrelin gene-derived peptides, and artificial
      analogues, suggesting that larger clinical trials are demanded to move ghrelin
      towards an available and reimbursed pharmaceutical intervention.

PMID- 22632861
TI  - Cachexia and oxidative stress in cancer: an innovative therapeutic management.
AB  - Cachexia influences morbidity, mortality and quality of life of cancer patients
      at advanced stage of disease. Therefore, the knowledge of its pathophysiology is
      critical to develop effective therapies to be integrated in the comprehensive
      approach of cancer patients. Oxidative stress, unless counteracted by effective
      antioxidant therapies, contributes to the development of anorexia and cachexia in
      cancer patients. In the present review the potential role of targeting oxidative
      stress in the treatment of cachexia is reported. Efficacy data on the use of
      antioxidants in advanced cancer patients are promising. However, the optimal
      dosage and route of administration as well as the timing and the most effective
      combination are not well established. Moreover, since cachexia is a
      multifactorial syndrome, targeting only oxidative stress as a contributing factor
      would be inadequate and likely to achieve a limited clinical therapeutic benefit.
      According to this rationale, antioxidants should be included as essential
      components of a multitargeted combined treatment of cancer cachexia, which has
      been shown to be the most successful approach for this syndrome.

PMID- 22632862
TI  - The use of herbal medicine in cancer-related anorexia/ cachexia treatment around
      the world.
AB  - Cancer-related cachexia, a condition in which the body is consumed by deranged
      carbohydrate, lipid and protein metabolism that is induced by inflammatory
      cytokines. Cachexia is associated with poor treatment outcome, fatigue and poor
      quality of life. Pharmacological intervention in the treatment and/or prevention
      of cachexia has been mainly aimed at the use of appetite enhancers to increase
      oral nutritional intake so far. Herbal remedies are part of traditional and folk
      healing methods with long histories of use. In this report, we have assessed
      which herbal approaches have had associated cancer cachexia case reports.
      Commonly used herbal medicines in western countries include essiac, iscador, pau
      d'arco tea, cannabinoids and so on. Some Kampo herbs and formulations are
      commonly used by cancer patients reduce the side effects and complications during
      the antitumor therapy. The relevant herbal medicines include ginseng, C. rhizome
      and radix astragali, and the related herbal remedies, such as TJ-48, TJ-41,
      PHY906 and Rikkunshito. However, there still have some adverse effects caused or
      amplified by herb and drug interactions that are difficult to separate. However,
      randomized effectiveness of herbal medicines shall be further identified in
      controlled clinical trials involving cancer patients with cachexia.

PMID- 22632863
TI  - Rikkunshito and ghrelin secretion.
AB  - Rikkunshito is a kampo herbal medicine which is widely used in Japan for the
      treatment of the upper gastrointestinal symptoms of patients with functional
      dyspepsia (FD), gastroesophageal reflux disease (GERD), dyspeptic symptoms of
      postgastrointestinal surgery patients, and chemotherapy-induced dyspepsia in
      cancer patients. Recently, very unique characteristics of rikkunshito have been
      unveiled; oral administration of rikkunshito potentiates orexigenic action of
      ghrelin through several different mechanisms. In addition, several lines of
      evidence obtained from both animal and human studies indicate that rikkunshito
      can be an attractive and promising therapeutic option for the anorectic
      conditions including cisplatin-induced dyspepsia, anorexia of aging, stress
      induced hypophagia, cancer cachexia-anorexia syndrome. In this review, we will
      highlight what is known about the orexigenic effect of rikkunshito with a special
      focus on an interaction with ghrelin signaling system.

PMID- 22632859
TI  - The use of ghrelin and ghrelin receptor agonists as a treatment for animal models
      of disease: efficacy and mechanism.
AB  - Ghrelin is a stomach-derived hormone that acts at the ghrelin receptor (formerly
      called the Growth Hormone Secretagogue (GHS)-1a receptor) in multiple tissues
      throughout the body, exhibiting pleotropic effects potentially beneficial as a
      treatment in human disease states. Given its properties including increasing
      appetite, decreasing systemic inflammation, decreasing vascular resistance,
      increasing cardiac output, and increasing growth hormone and IGF-1 levels,
      ghrelin has been tested as a treatment in animal models of multiple disease
      states that produce the deficits in these processes. Thus, the efficacy of
      ghrelin has been testing in diseases involving anorexia, negative energy balance,
      cardiovascular compromise, systemic inflammation and gastroparesis. These
      diseases include cancer cachexia, chronic heart failure, chronic renal failure,
      chemotherapy, arthritis, gastroparesis and inflammatory bowel disease. Across
      this wide variety of diseases treatment with ghrelin and ghrelin agonists have
      produced benefits, though given ghrelin's widespread effects, the exact
      mechanisms behind ghrelin's action in these settings is frequently difficult to
      determine. Further investigation using animal models may help to determine
      mechanisms that are most operative in these disease states and narrow treatment
      parameters helpful for human application.

PMID- 22632864
TI  - A review of traditional Japanese medicines and their potential mechanism of
      action.
AB  - Traditional Japanese herbal, or Kampo medicine was developed and modified from
      Chinese herbal medicine. After the Japanese government approved Kampo for
      clinical use, much attention has been paid to establishing scientific evidence
      for the effectiveness of these medicines. Recent progress has been made in
      elucidating the mechanisms of action of some types of Kampo medicine, including
      rikkunshito (RKT), daikenchuto, and yokukansan. In this review, we focused on
      identifying the target molecules and the active ingredients of RKT. Thus far,
      many target molecules have been implicated in the mechanism of action of Kampo
      medicines, such as ion channels, enzymes, and receptors. In particular, G protein
      coupled receptors are attractive candidates for explaining herbal medicine
      activity. This is particularly true of RKT, which is composed of 8 independent,
      crude drug extracts. Recent reports have shown that RKT elicits its effects
      through dual action to the G protein-coupled receptors: inhibition of
      serotonergic 5-HT2C and 5-HT2B receptors and activation of ghrelin receptors via
      specific ingredients of RKT. In addition, we suggest that the identification of
      the effective ingredients from Kampo medicines could contribute to the discovery
      and development of new drugs by means of modern high-throughput drug screening
      technology.

PMID- 22632865
TI  - Neurohormones, rikkunshito and hypothalamic neurons interactively control
      appetite and anorexia.
AB  - Ghrelin is the orexigenic peptide produced in the periphery, and its plasma level
      shows remarkable pre/postprandial changes. Ghrelin is considered a pivotal signal
      to the brain to stimulate feeding. Hence, characterizing the target neurons for
      ghrelin in the hypothalamic feeding center and the signaling cascade in the
      target neurons are essential for understanding the mechanisms regulating
      appetite. Anorexia and cachexia associated with gastric surgery, stress-related
      diseases, and use of anti-cancer drugs cause the health problems, markedly
      deteriorating the quality of life. The anorexia involves several
      neurotransmitters and neuropeptides in the hypothalamic feeding center, in which
      corticotropin-releasing hormone (CRH), urocortine, serotonin (5HT) and brain
      derived neurotrophic factor (BDNF) play a pivotal role. A Japanese herbal
      medicine, rikkunshito, has been reported to ameliorate the anorexia by promoting
      the appetite. This review describes 1) the interaction of ghrelin with the
      orexigenic neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC)
      and underlying signaling cascade in NPY neurons, 2) the anorectic pathway driven
      by BDNF-CRH/urocortine and 5HTCRH/ urocortine pathways, 3) the effect of
      rikkunshito on the interaction of ghrelin and NPY neurons in ARC, and 4) the
      effect of rikkunshito on the interaction of 5HT on CRH neurons in paraventricular
      nucleus (PVN).

PMID- 22632866
TI  - Cachexia and herbal medicine: perspective.
AB  - Kampo, a form of traditional herbal medical practice, has become a substance of
      interest for scientific research. Although earlier clinical reports concerning
      Kampo are abundant, the scientific investigation of Kampo has a very short
      history. However, the process of acquiring quantifiable clinical trial evidence
      on herbal medicine is now clearly underway. The development of multi-component
      herbal medicines capable of targeting multiple sites could be useful both for
      future drug discovery and for the potential management of complex diseases.
      Additionally, mechanistic studies and the identification of active compounds
      could lead to new discoveries in the biological and biomedical sciences. Modern
      translational research on herbal medicines beyond basic science and clinical
      perspectives will contribute to the development of new medicines. This review
      covers the translational aspects of herbal medicine with a focus on cancer
      anorexiacachexia. The review gives perspective on a new horizon for herbal
      medicine from a scientific point of view and a basis for the further development
      of complementary and alternative medicine (CAM) for patients.

PMID- 22632867
TI  - Objective pain diagnostics: clinical neurophysiology.
AB  - Neurophysiological techniques help in diagnosis, prognosis and treatment of
      chronic pain, and are particularly useful to determine its neuropathic origin.
      According to current standards, the diagnosis of definite neuropathic pain (NP)
      needs objective confirmation of a lesion or disease of somatosensory systems,
      which can be provided by neurophysiological testing. Lesions causing NP mostly
      concern the pain-temperature pathways, and therefore neurophysiological
      procedures allowing the specific testing of these pathways (i.e., A-delta and C
      fibres, spino-thalamo-cortical tracts) are essential for objective diagnosis.
      Different techniques to stimulate selectively pain-temperature pathways are
      discussed. Of these, laser-evoked potentials (LEPs) appear as the easiest and
      most reliable neurophysiological method of assessing nociceptive function, and
      their coupling with autonomic responses (e.g., galvanic skin response) and
      psychophysics (quantitative sensory testing - QST) can still enhance their
      diagnostic yield. Neurophysiological techniques not exploring specifically
      nociception, such as standard nerve conduction velocities (NCV) and SEPs to non
      noxious stimulation, should be associated to the exploration of nociceptive
      systems, not only because both may be simultaneously affected to different
      degrees, but also because some specific painful symptoms, such as paroxysmal
      discharges, may depend on specific alteration of highly myelinated A-beta fibres.
      The choice of techniques is determined after anamnesis and clinical exam, and
      tries to answer a number of questions: (a) is the pain-related to injury of
      somatosensory pathways?; (b) to what extent are different subsystems affected?;
      (c) are mechanisms and lesion site in accordance with imaging data?; (d) are
      results of use for diagnostic or therapeutic follow-up? Neuropathic pain (NP)
      affects more than 15 million people in Western countries, and its belated
      diagnosis leads to insufficient or delayed therapy. The use of neurofunctional
      approaches to obtain a "physiological photograph" of somatosensory function is
      therefore highly relevant, as it yields significant clues about the type and
      mechanisms of pain, thus prompting rapid and optimised therapy.

PMID- 22632868
TI  - Pain-related evoked potentials: a comparative study between electrical
      stimulation using a concentric planar electrode and laser stimulation using a CO2
      laser.
AB  - OBJECTIVE: To compare the pain-related evoked potentials (PREPs) obtained by
      superficial electrical stimulation using a concentric planar electrode to those
      obtained by CO2 laser stimulation. METHODS: In 12 healthy subjects, PREPs,
      sympathetic skin reflexes (SSRs), motor reaction times (mRTs), and the conduction
      velocity (CV) of the recruited nerve fibres were assessed in response to
      electrical and laser stimulation. RESULTS: In response to superficial electrical
      stimulation, PREP latencies and mRTs were shorter, while PREP amplitude tended to
      be increased. By contrast, SSR amplitudes and latencies and estimated CVs of the
      stimulated nerve fibres did not differ between electrical and laser stimulation.
      Fifteen minutes after PREP recordings, the residual pain intensity and the degree
      of unpleasantness were higher for laser stimulation than for electrical
      stimulation. In addition, CO2 laser stimuli induced dyschromic spots on the skin.
      For these reasons, all subjects declared that they would prefer superficial
      electrical stimulation rather than CO2 laser stimulation if they had to perform
      PREPs again. CONCLUSIONS: The estimated CVs of the recruited nerve fibres and the
      localized pinprick sensation felt by the subjects suggest that small-diameter
      fibres in the A-delta range, conveying "first-pain" information, were stimulated
      in response to superficial electrical stimulation as for laser stimulation.
      Superficial electrical stimulation using a concentric planar electrode could be a
      valuable alternative to laser stimulation for assessing PREPs in the practice of
      clinical neurophysiology.

PMID- 22632869
TI  - Spatiotemporal source analysis in scalp EEG vs. intracerebral EEG and SPECT: a
      case study in a 2-year-old child.
AB  - OBJECTIVE: This case study aims to demonstrate that spatiotemporal spike
      discrimination and source analysis are effective to monitor the development of
      sources of epileptic activity in time and space. Therefore, they can provide
      clinically useful information allowing a better understanding of the
      pathophysiology of individual seizures with time- and space-resolved
      characteristics of successive epileptic states, including interictal, preictal,
      postictal, and ictal states. METHODS: High spatial resolution scalp EEGs (HR-EEG)
      were acquired from a 2-year-old girl with refractory central epilepsy and single
      focus seizures as confirmed by intracerebral EEG recordings and ictal single
      photon emission computed tomography (SPECT). Evaluation of HR-EEG consists of the
      following three global steps: (1) creation of the initial head model, (2)
      automatic spike and seizure detection, and finally (3) source localization.
      During the source localization phase, epileptic states are determined to allow
      state-based spike detection and localization of underlying sources for each
      spike. In a final cluster analysis, localization results are integrated to
      determine the possible sources of epileptic activity. The results were compared
      with the cerebral locations identified by intracerebral EEG recordings and SPECT.
      RESULTS: The results obtained with this approach were concordant with those of
      MRI, SPECT and distribution of intracerebral potentials. Dipole cluster centres
      found for spikes in interictal, preictal, ictal and postictal states were
      situated an average of 6.3mm from the intracerebral contacts with the highest
      voltage. Both amplitude and shape of spikes change between states. Dispersion of
      the dipoles was higher in the preictal state than in the postictal state. Two
      clusters of spikes were identified. The centres of these clusters changed
      position periodically during the various epileptic states. CONCLUSION: High
      resolution surface EEG evaluated by an advanced algorithmic approach can be used
      to investigate the spatiotemporal characteristics of sources located in the
      epileptic focus. The results were validated by standard methods, ensuring good
      spatial resolution by MRI and SPECT and optimal temporal resolution by
      intracerebral EEG. Surface EEG can be used to identify different spike clusters
      and sources of the successive epileptic states. The method that was used in this
      study will provide physicians with a better understanding of the
      pathophysiological characteristics of epileptic activities. In particular, this
      method may be useful for more effective positioning of implantable intracerebral
      electrodes.

PMID- 22632870
TI  - Effects of acupuncture needle penetration on motor system excitability.
AB  - OBJECTIVES: Transcranial magnetic stimulation (TMS) studies reported changes in
      motor evoked potential amplitude after acupuncture needling both at traditional
      acupoints and non-acupoints. However, the effects of needle penetration per se
      have not yet been investigated with TMS. The present study aimed at exploring
      effects of deep manual acupuncture needling compared to a state-of-the-art, non
      penetrating control condition on several standard TMS measures of motor system
      excitability. METHODS: Twenty healthy volunteers received both verum and sham
      acupuncture applied at the acupoint GB 34 near the right knee, using a crossover
      design. A needle with a retractable tip ("Streitberger needle") was used as sham
      condition to minimize non-specific effects. TMS parameters (resting motor
      threshold, active motor threshold, cortical silent period, short intracortical
      inhibition, and intracortical facilitation) were calculated from the abductor
      digiti minimi (ADM) of both hands 15 min before and after needling by a
      researcher blind to the treatment condition. RESULTS: Verum compared to sham
      acupuncture significantly increased resting motor threshold. No significant
      treatment effect was found for any other measure, though cortical silent period
      and intracortical facilitation showed trends to increase in the hemisphere
      contralateral to the needling site after verum acupuncture. CONCLUSIONS: These
      results suggest a subtle but specific inhibitory effect of acupuncture needle
      penetration at acupoint GB 34 on motor system excitability. Further
      investigations should be performed with a particular emphasis on the measurements
      of resting motor threshold, cortical silent periods and intracortical
      facilitation.

PMID- 22632871
TI  - The relationship of pre- and postoperative median and ulnar nerve conduction
      measures to a self-administered questionnaire in carpal tunnel syndrome.
AB  - STUDY AIMS: Following carpal tunnel release (CTR), only very modest correlations
      have been found between subjective symptoms and function indexes compared to
      neurophysiological measures. The objective of this study was to evaluate this
      relationship by comparing the self-administered Boston symptom severity score and
      function severity score questionnaire against nerve conduction studies (NCS)
      before and after CTR using two different electrophysiological techniques.
      PATIENTS AND METHODS: Carpal tunnel release was performed in 51 patients (62
      hands). Pre- and postoperative NCS were evaluated using both conventional
      neurophysiological methods and by means of a new hand-held device. RESULTS:
      Preoperatively there was almost no correlation between symptom severity and
      function scores and NCS results. Following surgery however, both symptom severity
      and function showed a modest, but significant improvement in their correlation to
      NCS (at highest r=0.405, P<0.01). This improvement in the relation of subjective
      measures to neurophysiological results was seen in both median nerve sensory and
      motor conduction as well as in ulnar nerve motor conduction. CONCLUSIONS: In
      addition to median-nerve dysfunction, it might be suggested that ulnar nerve
      changes can contribute to symptoms of carpal tunnel syndrome in patients. Several
      associations were found using a median-ulnar sensory latency difference in the
      finger-wrist segment and a sensory conduction difference in the palm to wrist
      segment. Significant correlations were established by both conventional NCS and
      the new hand-held device.

PMID- 22632872
TI  - Correlation of current perception threshold and somatosensory evoked potential in
      diabetes.
AB  - OBJECTIVE: To study the relationship between current perception threshold (CPT)
      and somatosensory evoked potential (SEP) in diabetes. METHODS: Both CPT and SEP
      were recorded in 66 diabetic patients. Both the CPT scores (measured at 2000 Hz,
      250 Hz, and 5 Hz stimulations) and SEP (peak latency at ERB's point [Lat (ERB)]
      and popliteal fossa [Lat (PF)]; interpeak latency of "ERB to 7th cervical
      vertebra" [Deltalat (ERB-C7)] and "popliteal fossa to lumbar vertebra" [Deltalat
      (PF-FO)]) were recorded in both upper and both lower limbs, separately. t-tests
      and correlation analyses were performed to assess relationships between CPT and
      SEP tests. RESULTS: After adjustment for height and/or age, CPT scores at 2000 Hz
      were significantly correlated with Lat (ERB) (left: rho=0.408, P<0.05; right:
      rho=0.297, P<0.05), Deltalat (ERB-C7) (left: rho=0.238, P<0.05; right: rho=0.385,
      P<0.05), and Lat (PF) (rho=0.216, P<0.05), and those at 250 Hz were moderately
      correlated with Lat (ERB) (left: rho=0.234, P<0.05; right: rho=0.306, P<0.05).
      CPT scores at 5 Hz were not significantly correlated with any SEP measurements
      (P>0.05). CONCLUSIONS: Both CPT scores at 2000 Hz and SEP may reliably determine
      large-fiber function in diabetic neuropathy.

PMID- 22632873
TI  - Digging deep into nucleic acid structure and nucleic acid protein recognition.

PMID- 22632874
TI  - Puberty and microvascular function in healthy children and adolescents.
AB  - OBJECTIVE: To determine the role of pubertal status on microvascular function in
      healthy children and adolescents. STUDY DESIGN: Children and adolescents (n =
      112; age 10-16 years) were investigated in 2 separate prospective cross-sectional
      studies. The main outcome measure was microvascular function, assessed by
      peripheral arterial tonometry to determine the reactive hyperemic index (RHI).
      Physical activity was assessed using 7-day recall in one study and accelerometry
      in the other study. Subjects were grouped based on their self-assessed pubertal
      status according to Tanner stage: group 1 (prepuberty, Tanner I), group 2 (mid
      puberty, Tanner II/III), and group 3 (late puberty, Tanner IV/V). Stepwise
      multiple regression analysis was performed to identify independent predictors of
      the RHI. RESULTS: Complete data were available for 94 subjects (55 females) with
      a median (IQR) age of 14 (3.0) years and a mean body mass index of 19.0 +/- 3.63
      kg.m(-2). Significant correlations with RHI were observed for Tanner stage (r =
      0.569; P < .001), age (r = 0.567; P < .001), stature (r = 0.553; P < .001),
      systolic blood pressure (r = 0.494; P < .001), and body mass index (r = 0.309; P
      = .001), but not for sex and moderate-to-vigorous physical activity. In stepwise
      regression analysis, pubertal status was the only independent predictor of
      microvascular function (R(2) = 0.242; beta = 0.492; P < .001). Prepubertal
      children (group 1) had a significantly lower RHI [1.14 (0.24)] compared with
      group 2 [1.65 (0.57)] and group 3 [1.70 (0.75)] (all P < .001). CONCLUSION:
      Pubertal status was the main predictor of microvascular function in healthy
      children and adolescents. Future studies investigating microvascular function in
      this age group should assess and control for pubertal maturation.

PMID- 22632875
TI  - Rapid onset of forehead mass in an infant.

PMID- 22632876
TI  - Factors associated with failure to screen newborns for retinopathy of
      prematurity.
AB  - OBJECTIVES: To evaluate ROP screening rates in a population-based cohort; and to
      identify characteristics of patients that were missed. STUDY DESIGN: We used the
      California Perinatal Quality Care Collaborative data from 2005-2007 for a cross
      sectional study. Using eligibility criteria, screening rates were calculated for
      each hospital. Multivariable regression was used to assess associations between
      patient clinical and sociodemographic factors and the odds of missing screening.
      RESULTS: Overall rates of missed ROP screening decreased from 18.6% in 2005 to
      12.8% in 2007. Higher gestational age (OR = 1.25 for increase of 1 week, 95% CI,
      1.21-1.29), higher birth weight (OR = 1.13; 95% CI, 1.10-1.15), and singleton
      birth (OR = 1.2; 95% CI, 1.07-1.34) were associated with higher probability of
      missing screening. Level II neonatal intensive care units and neonatal intensive
      care units with lower volume were more likely to miss screenings. CONCLUSION:
      Although ROP screening rates improved over time, larger and older infants are at
      risk for not receiving screening. Furthermore, large variations in screening
      rates exist among hospitals in California. Identification of gaps in quality of
      care creates an opportunity to improve ROP screening rates and prevent impaired
      vision in this vulnerable population.

PMID- 22632877
TI  - Near-fatal asthma: an ounce of prevention may be worth more than a pound of cure.

PMID- 22632878
TI  - The effect of age on whole blood interferon-gamma release assay response among
      children investigated for latent tuberculosis infection.
AB  - OBJECTIVE: To evaluate the effect of age upon QuantiFERON-TB Gold-In-Tube (QFT
      IT) assay outcome among children examined for latent tuberculosis infection
      (LTBI). STUDY DESIGN: A cross-sectional study was conducted among 761 children
      (mean age +/- SD: 7.84 +/- 4.68 years) evaluated for LTBI. Participants were
      examined with both tuberculin skin test and QFT-IT (Cellestis, Australia) and
      categorized into 4 age groups. Multivariate logistic and linear regressions were
      used to evaluate the association between selected demographic and patient
      characteristics upon the qualitative and quantitative QFT-IT outcomes. Agreement
      between the tuberculin skin test and QFT-IT within groups was evaluated with the
      kappa statistic. RESULTS: QFT-IT indeterminate results occurred more frequently
      among young children (8.1%; P < .0001) and children (2.7%; P = .025) than
      adolescents (0.7%). Among QFT-IT positive patients, infants had higher mean (+/-
      SD) interferon-gamma (IFNgamma) concentration than adolescents. QFT-IT positive
      (vs negative) outcome was associated with origin from a high tuberculosis
      endemicity setting (AOR = 4.54; 95% CI, 3.22-6.25) and lack of previous Bacille
      Calmette Guerin immunization (AOR = 2.70; 95% CI, 1.89-3.85), but not patient age
      (AOR = 0.96; 95% CI, 0.92-0.99). However, among QFT-IT positive patients, the
      IFNgamma concentration was inversely associated with patient age (P = .009) and
      positively with mitogen response (P = .0002). Agreement between tests was not
      significantly different between younger and older children in the different risk
      groups. CONCLUSIONS: Qualitative QFT-IT assay results are not affected by patient
      age. However, indeterminate results occur more frequently among younger children.
      Among patients with LTBI the quantitative QFT-IT result (ie, IFNgamma) is
      inversely associated with patient age.

PMID- 22632879
TI  - Short and midterm outcomes of elective total aortic arch replacement combined
      with coronary artery bypass grafting.
AB  - BACKGROUND: This study was performed to investigate the early and late outcomes
      of total aortic arch replacement (TAR) with or without coronary artery bypass
      grafting (CABG). METHODS: From October 1999 to December 2010, 200 consecutive
      patients underwent elective TAR for nondissecting aneurysm through a median
      sternotomy. Of this number, 131 (65.5%) had isolated TAR (TAR group) and 69
      (34.5%) underwent concomitant CABG (TAR/CABG group). Patients in the TAR/CABG
      group were older and had more advanced chronic kidney disease and higher
      additive/logistic European System for Cardiac Operative Risk Evaluation and Japan
      scores than patients in the TAR group. RESULTS: Overall 30-day mortality was 0.5%
      (1 of 200) and hospital mortality was 3.5% (7 of 200). Hospital mortality was
      1.5% (2 of 131) in the TAR group and 7.2% (5 of 69) in the TAR/CABG group
      (p=0.036). Multivariate analysis showed that operation time (odds ratio [OR]
      1.01, p=0.013) was a risk factor for hospital mortality, but failed to
      demonstrate concomitant CABG as a risk factor. Cox proportional hazard analysis
      showed that age (OR 1.08, p=0.05), female sex (OR 3.58, p=0.0004), chronic kidney
      disease (OR 7.70, p<0.0001), and operation time (OR 1.01, p=0.0002) were risk
      factors for midterm mortality, whereas concomitant CABG was not (OR 0.92,
      p=0.87). There was a significant difference in midterm survival and freedom from
      major cerebrocardiovascular events in the TAR group versus the TAR/CABG group.
      CONCLUSIONS: Concomitant CABG was not a risk factor for hospital morality with
      TAR. However, patients with concomitant CABG have more preoperative
      comorbidities, which may adversely affect outcomes, and which may therefore
      deserve special attention.

PMID- 22632880
TI  - The role of surgical management in recurrent thymic tumors.
AB  - BACKGROUND: There are few data on outcomes after surgical treatment for recurrent
      thymic tumors. The aim of this study is to analyze and compare long-term outcomes
      of treatments for recurrent thymic tumors. METHODS: Between January 1956 and
      December 2009, 344 thymic tumors were surgically resected (309 thymomas, 22
      thymic carcinomas, 12 thymic carcinoids, and 1 thymolipoma). There were 48
      recurrences (13.9%): 30 thymomas, 9 thymic carcinomas, and 9 thymic carcinoids.
      There were 27 men and 21 women with a median age of 51 years (range, 27 to 83).
      Retrospective chart review was performed. Relevant factors for recurrence as well
      as survival and progression-free interval were analyzed. RESULTS: The median
      follow-up interval from the initial operation was 83 months (range, 9 to 515).
      Recurrence adversely affected overall survival in surgically resected thymic
      tumors (p = 0.0014). In multivariate analysis, the initial Masaoka stage,
      incomplete resection, and World Health Organization histology were significant
      risk factors for recurrence. In multivariate analysis, only surgical management
      was associated with prolonged survival p = 0.0038) and improved progression-free
      interval (p = 0.0378) in recurrent thymoma. Five-year survival after recurrent
      thymoma was 54%. For recurrent thymic carcinoma, surgery did not improve
      survival. For these patients, chemotherapy was associated with improved
      progression-free interval after recurrence (p = 0.0295). There were no 5-year
      survivors of recurrent thymic carcinoma. CONCLUSIONS: Our data suggest that
      surgical management is associated with better outcome and is the treatment of
      choice for recurrent thymoma. For recurrent thymic carcinoma, surgical management
      has a very limited role, and chemotherapy appears to be a more effective
      treatment modality.

PMID- 22632881
TI  - Trends in the indications and survival in pediatric heart transplants: a 24-year
      single-center experience in 307 patients.
AB  - BACKGROUND: Heart transplantation is the only viable treatment for children with
      end-stage heart failure due to congenital heart disease (CHD) or cardiomyopathy.
      This study reviewed the trends in the indications for transplant and survival
      after transplant during the past 24 years. METHODS: A retrospective review was
      performed of the 307 heart transplants performed at our center since 1986. To
      analyze the trends in the indications for transplant as well as operative death
      and late-survival, the data were divided into three periods in 8-year increments:
      1986 to 1993 (50 patients), 1994 to 2001 (116 patients), and 2002 to 2009 (141
      patients). RESULTS: The indications for transplantation were 39% cardiomyopathy,
      57% CHD, and 4% retransplant. Of the 173 with CHD, 139 (80%) had single-ventricle
      (SV) anomalies. In the CHD group, transplantation for failed SV palliation,
      including Fontan procedure, became the predominant indication in the last 8-year
      interval of our program. Survival after transplant was the best in patients with
      cardiomyopathy and the worst in patients with failed palliations for SV
      anomalies, including failed Fontan procedures. CONCLUSIONS: Transplantation for
      heart failure related to failed SV palliation has become the most common
      indication for patients with CHD. The high-risk nature of these transplants will
      have significant implications for heart transplant programs as more infants with
      SV anomalies survive palliative procedures performed during infancy.

PMID- 22632882
TI  - Primary neuroendocrine tumors of the thymus: a multicenter experience of 35
      patients.
AB  - BACKGROUND: Primary neuroendocrine tumors of the thymus (NETT) are rare tumors
      and represent a distinct category of tumors collectively displaying morphologic
      and biological neuroendocrine features. We sought to evaluate factors influencing
      long-term survival in patients with primary NETT. METHODS: From January 1990 to
      April 2011, 35 patients (27 male patients and 8 female patients) were surgically
      treated for primary NETT at 5 institutions. RESULTS: No operative (30-day)
      mortality occurred. Morbidity was 37.14% (13/35 patients). All patients were
      followed for a total of 2,703 months. Fourteen patients had associated
      paraneoplastic syndrome. Twenty-four patients are alive, 19 of whom are free of
      disease and 5 of whom continue to have disease. The median overall survival was
      153 months. The overall 5-year and 10-year actuarial survival rates were 84.34%
      and 60.82%, respectively. The 10-year survival was evaluated according to
      histologic type (typical carcinoid, 77.92%; atypical carcinoid, 54.55%; large
      cell neuroendocrine carcinomas, 0%; Masaoka staging (stage I, 100%; stage II,
      66.67%; stage III, 61.9%; stage Iva, 25%; stage IVb, 0%), presence of
      paraneoplastic syndrome (no = 70.67%; yes = 32.14%), postoperative radiotherapy
      (yes = 39.71%; no = 85.71.%), Surveillance, Epidemiology, and End Results (SEER)
      staging system (localized disease, 83.3%; regional disease, 53.3%; distant
      disease, 0%), tumor size (<7 cm = 90.9%; >=7cm = 28.7%; p = 0.0007), and Ki67
      expression, which was available in 23 patients (<10% = 85.71%; >=10% = 0%; p =
      0.0037). CONCLUSIONS: The prognosis of primary NETT is statistically
      significantly related to tumor size >7 cm and to the proliferation index
      (evaluated by Ki67 expression >10%). The histologic type of the neoplasm, the
      presence of a paraneoplastic syndrome, the Masaoka staging, the evidence of
      distant disease, and postoperative radiotherapy also impact prognosis.

PMID- 22632883
TI  - Nutrient-rich meat proteins in offsetting age-related muscle loss.
AB  - From a health perspective, an underappreciated consequence of the normal aging
      process is the impacts that the gradual loss of skeletal muscle mass, termed
      sarcopenia, has on health beyond an effect on locomotion. Sarcopenia, refers to
      the loss of muscle mass, and associated muscle weakness, which occurs in aging
      and is thought to proceed at a rate of approximately 1% loss per year. However,
      periods of inactivity due to illness or recovery from orthopedic procedures such
      as hip or knee replacement are times of accelerated sarcopenic muscle loss from
      which it may be more difficult for older persons to recover. Some of the
      consequences of age-related sarcopenia are easy to appreciate such as weakness
      and, eventually, reduced mobility; however, other lesser recognized consequences
      include, due to the metabolic role the skeletal muscle plays, an increased risk
      for poor glucose control and a predisposition toward weight gain. What we
      currently know is that two stimuli can counter this age related muscle loss and
      these are physical activity, specifically resistance exercise (weightlifting),
      and nutrition. The focus of this paper is on the types of dietary protein that
      people might reasonably consume to offset sarcopenic muscle loss.

PMID- 22632884
TI  - Acute aortic dissection: an update.
AB  - The aorta, which has a complex intrinsic biology and sophisticated mechanical
      properties for conducting the blood ejected from the left ventricle to the rest
      of the systemic arterial bed, is the largest and strongest artery in the body. It
      carries roughly 200 million liters of blood in an average lifetime. Any process
      that undermines the architecture threatens the structure, stability, and
      functionality of the aorta. In this regard, acute aortic dissection (AAD)
      requires special attention because it is the most catastrophic acute illness of
      the aorta; it has high morbidity and mortality because of potentially fatal
      complications. AAD has, therefore, become an important topic of recent research,
      and knowledge about this disease has improved during the past few years. Up-to
      date knowledge about the natural history, epidemiology, presentation,
      physiopathology, evolution, management, follow-up, and long-term outcomes of AAD
      are summarized in this review.

PMID- 22632885
TI  - Fluconazole exposure rather than clonal spreading is correlated with the
      emergence of Candida glabrata with cross-resistance to triazole antifungal
      agents.
AB  - The emergence of antifungal resistance in Candida species has raised concern in
      recent years, especially resistance toward triazole. Several newer triazole
      antifungal agents have been introduced which have a broader spectrum for fungal
      infections, such as voriconazole. However, cross-resistance among triazoles is a
      major concern with regard to their clinical application. Antifungal
      susceptibility was performed using E-test for 166 clinical isolates (29 blood and
      137 nonblood isolates) in 2003 and 2004. We applied pulsed-field gel
      electrophoresis for genotyping. Ninety isolates of C. albicans, 47 isolates of C.
      tropicalis, 27 isolates of C. glabrata, and two isolates of C. krusei were
      included. All isolates were susceptible to amphotericin B. Eleven (40.7%) of the
      27 C. glabrata had intermediate resistance to caspofungin. Forty-seven (28.3%) of
      the 166 isolates were not susceptible to fluconazole, including two C. albicans,
      16 C. tropicalis, 27 C. glabrata, and two C. krusei isolates. All except seven of
      the C. glabrata isolates were susceptible to voriconazole. All the triazole drugs
      had a positive correlation among their minimum inhibitory concentrations (MICs).
      Fluconazole MIC was a good predictor for susceptibility to voriconazole, as
      determined using a receiver operating characteristic curve. Furthermore, a high
      diversity of pulsotypes for the 27 clinical isolates of C. glabrata was observed.
      Previous fluconazole exposure within 3 months was associated with reduced
      triazole susceptibility for C. glabrata. We demonstrated a significant positive
      correlation of MIC values among the four tested triazole drugs. No amphotericin B
      and caspofungin resistant isolates were found in this study. The cross-resistance
      to triazole among C. glabrata isolates was associated with previous fluconazole
      exposure as opposed to clonal spreading. Selection pressure due to fluconazole
      use may play a major role in triazole cross-resistance.

PMID- 22632886
TI  - The alteration of plasma TGF-beta1 levels in patients with brain tumors after
      tumor removal.
AB  - Transforming growth factor (TGF) beta1 may be a candidate for a serologic tumor
      marker. In this study, the plasma levels of TGF-beta1 in patients with brain
      tumors were measured using enzyme-linked immunosorbent assay before and after
      tumor removal. Patients were divided into four groups, the control group and the
      benign, malignant, and metastatic brain tumor groups. All brain tumor groups
      showed significant increases in the levels of TGF-beta1 before tumor removal
      (6.36 +/- 3.94, 17.0 +/- 9.7, and 12.2 +/- 10.3 ng/ml for the benign, malignant,
      and metastatic groups, respectively). When compared with the results obtained in
      the control group (1.12 +/- 0.74 ng/ml), significant decreases in TGF-beta1
      concentrations after total tumor removal were found in both the benign and
      malignant brain tumor groups (2.55 +/- 2.00 and 8.93 +/- 5.73 ng/ml,
      respectively; p = 0.0001 and p = 0.003, respectively). On the other hand, plasma
      TGF-beta1 levels in the metastatic brain tumor group showed a slight but
      significant increase (14.7 +/- 9.3 ng/ml, p = 0.035) after tumor removal. In a
      case of low-grade astrocytoma, plasma levels of TGF-beta1 were found to be 3.6
      and 1.1 ng/ml before and after tumor removal, respectively. However, recurrent
      tumor was noted in this patient 7 months later, and the levels of TGF-beta1 were
      26.2 and 8.4 ng/ml before and after the second operation, respectively. The data
      show that plasma TGF-beta1 was elevated in the circulation of patients with brain
      tumors and that significant decreases in TGF-beta1 levels were observed after the
      removal of benign and malignant tumors. The results also suggest that TGF-beta1
      may be a useful serologic marker for brain tumors.

PMID- 22632887
TI  - Comparison of secondary signs as shown by unenhanced helical computed tomography
      in patients with uric acid or calcium ureteral stones.
AB  - Unenhanced helical computed tomography (UHCT) has evolved into a well-accepted
      diagnostic method in patients with suspected ureterolithiasis. UHCT not only
      shows stones within the lumen of the ureter, it also permits evaluation of the
      secondary signs associated with ureteral obstruction from stones. However, there
      we could find no data on how secondary signs might differ in relation to
      different compositions of ureteral stones. In this study, we compared the degree
      of secondary signs revealed by UHCT in uric acid stone formers and in patients
      forming calcium stones. We enrolled 117 patients with ureteral stones who
      underwent UHCT examination and Fourier transform infra-red analysis of stone
      samples. Clinical data were collected as follows: age, sex, estimated glomerular
      filtration rate (eGFR), urine pH, and radiological data on secondary signs
      apparent on UHCT. The uric acid stone formers had significantly lower urine pH
      and eGFR in comparison to calcium stone formers, and on UHCT they also had a
      higher percentage of the secondary signs, including rim sign (78.9% vs. 60.2%),
      hydroureter (94.7% vs. 89.8%), perirenal stranding (84.2% vs. 59.2%) and kidney
      density difference (73.7% vs. 50.0%). The radiological difference was
      statistically significant for perirenal stranding (p=0.041). In conclusion, we
      found that UHCT scanning reveals secondary signs to be more frequent in patients
      with uric acid ureteral stones than in patients with calcium stones, a tendency
      that might result from an acidic urine environment.

PMID- 22632888
TI  - Lymphovascular invasion is a pathological feature related to aggressive cancer
      behavior and predicts early recurrence in prostate cancer.
AB  - In order to determine the prognostic impact of lymphovascular invasion (LVI) in
      patients after radical prostatectomy, the retrospective data from our institution
      has been analyzed. From 1998 to 2010, 117 patients underwent radical
      prostatectomy. A total of 87 patients were included in this retrospective study.
      The relationship between LVI and advanced prostate cancer characteristics was
      evaluated by chi(2) test. The Kaplan-Meier method and meta-analysis were used to
      describe the impact of LVI invasion upon early biochemical failure after radical
      prostatectomy. LVI was observed in patients with clinically or pathologically
      aggressive prostate cancer including patients of higher preoperative risk group,
      higher preoperative PSA, advanced Gleason grade, and pathological T3 disease. LVI
      is also associated with early biochemical failure rate both in our report and in
      the literature. Therefore, LVI is a pathological feature which indicates
      prognosis correlates with aggressive prostate cancer behavior and results in
      early biochemical failure after radical prostatectomy.

PMID- 22632889
TI  - The physician compliance of red blood cell transfusion by computerized
      transfusion decision support system.
AB  - "When should we trigger a transfusion?" is always a critical question between the
      patient's benefits and risks in red blood cell (RBC) transfusion. A computerized
      transfusion decision support system (CTDSS) has been used since September 2004 in
      an academic medical center with 1400 beds. In this study, the factors affecting
      RBC transfusion were investigated. In total 20,551 RBC-transfusion episodes
      between January and December 2008 were reviewed. The nearest hemoglobin
      concentration before transfusion is defined as the transfusion trigger. The
      physician compliance, the factors associated with the transfusion triggers and
      posttransfusion hemoglobin increment were investigated. The physician compliance
      is 83.1%. The transfusion trigger is 8.32 +/- 1.84 (mean +/- standard deviation)
      g/dL. The transfusion triggers are statistically significant in terms of both
      different order sources and disease types (p<0.05).The posttransfusion hemoglobin
      level increased in two-thirds of the episodes. The percentages of hemoglobin
      increments after transfusion are dependent on the transfusion triggers.
      Appropriate transfusion practice may reduce the overuse of blood components and
      improve transfusion quality. CTDSS should be more powerful to intervene in the
      appropriateness of transfusion practice.

PMID- 22632890
TI  - Incidence and clinical significance of zygomaticomaxillary complex fracture
      involving the temporomandibular joint with emphasis on trismus.
AB  - Trismus is frequently a sequel of temporomandibular joint (TMJ) involvement in a
      zygomaticomaxillary complex (ZMC) fracture. Although trismus is commonly observed
      in patients with ZMC fracture, continuous follow-up examinations of their degree
      of mouth opening have rarely been documented. The aim of this retrospective study
      was to determine the incidence and clinical significance of ZMC fracture
      involving the glenoid fossa or articular eminence of the TMJ with an emphasis on
      trismus. The medical and computed tomography (CT) imaging data of 28 patients
      with ZMC fracture treated by oral and maxillofacial surgeons (OMFSs) (OMFS group)
      and 174 patients with ZMC fracture treated by surgeons other than OMFSs (non-OMFS
      group) between May 2002 and May 2006 were reviewed. Maximal interincisal opening
      (MIO) less than 35 mm or three-finger width was considered limited mouth opening
      and indicative of trismus. Preoperative CT imaging data indicated that about 64%
      (18/28) and 50% (87/174) of the patients in the OMFS and non-OMFS groups,
      respectively, had a ZMC fracture involving the TMJ. Among these OMFS patients, 17
      (94.40%) patients had limited mouth opening (MIO range, 7-33 mm) preoperatively,
      which improved markedly postoperatively. Among the non-OMFS patients with such
      fractures, 42 (48.3%) patients had trismus preoperatively and two retained
      trismus postoperatively. Lack of proper preoperative CT images, inadequate
      postoperative follow-up protocol, and/or neglect by patients and medical staff
      could influence the outcomes of ZMC fracture involving the TMJ. We make
      recommendations for reducing the risk of complications subsequent to ZMC fracture
      involving the TMJ.

PMID- 22632891
TI  - Multiple endocrine neoplasia type 2A.
AB  - Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant inherited
      cancer syndrome that expresses nonendocrine and endocrine tumors. Here, we
      describe a 42-year-old man with an initial presentation of low back pain and
      hypertension. Clinical assessments revealed pheochromocytoma, medullary thyroid
      carcinoma with bone metastasis, and parathyroid hyperplasia. MEN 2A was
      diagnosed, and a family history of pheochromocytoma was traced. Surgical
      resection of the pheochromocytoma of the adrenal gland resulted in a cure of the
      patient's hypertension. He received systemic chemotherapy with the "MAID" regimen
      (mesna, doxorubicin, ifosfamide, and dacarbazine) over three cycles of 3 weeks
      each, and showed a partial response.

PMID- 22632892
TI  - Fracture of VerSys fully bead-coated long femoral stems: report on four fractures
      in 41 hips.
AB  - The fracture of uncemented, fully porous, coated femoral stems is a rare
      complication that develops after primary total hip arthroplasty, and it is even
      rarer after revision surgery. To the best of our knowledge, cases of only 10
      broken fully coated stems have been reported. This is the first report on
      fracture of the VerSys fully bead-coated femoral stem, which is designed for
      diaphyseal fixation and for application in revision surgery or when a proximal
      fixation is not feasible. Between 2000 and 2008, we implanted 41 VerSys fully
      coated stems in 40 patients. We present four cases of femoral stem fractures at
      23, 31, 40, and 86 months after surgery. The common risk factors for these four
      patients were inadequate support for the implant in the proximal femur due to
      nonunion in this area, a stem diameter <=12 mm, and a relatively young age.

PMID- 22632893
TI  - Giant cell tumor of the parotid gland.

PMID- 22632895
TI  - Medialization of the subscapularis footprint does not affect functional outcome
      of arthroscopic repair.
AB  - PURPOSE: The purpose of this study was to compare the functional outcome of
      arthroscopic subscapularis repair of complete subscapularis tendon tears
      performed with anatomic tendon-to-bone repair versus repair with medialization of
      the footprint. METHODS: A retrospective review was performed of subscapularis
      tendon tears repaired with an arthroscopic technique from 1998 to 2009. Complete
      tears of 100% of the length of the subscapularis tendon repaired arthroscopically
      were included in the study. The exclusion criteria included subscapularis tendon
      tears of less than 100% of the tendon length, revision repairs, or open repairs.
      The minimum follow-up was 2 years. Postoperative functional outcome was
      determined by University of California, Los Angeles and American Shoulder and
      Elbow Surgeons scores. RESULTS: Group I comprised 14 tears that were anatomically
      repaired to the normal lesser tuberosity footprint. Group II comprised 9 tears
      that were repaired to the lesser tuberosity after medialization of the footprint.
      There was no difference in improvement in University of California, Los Angeles
      or American Shoulder and Elbow Surgeons scores between the 2 groups (P > .05).
      Furthermore, there was no difference in how patients rated their shoulder,
      patient satisfaction, or return to activity between the 2 groups (P > .05).
      CONCLUSIONS: On the basis of this study, functional outcome does not appear to be
      compromised by medialization of the subscapularis footprint. Medialization by 4
      to 7 mm is acceptable when tendon mobility is otherwise insufficient to perform
      an anatomic tendon-to-bone repair of a complete subscapularis tendon tear. LEVEL
      OF EVIDENCE: Level III, retrospective comparative study.

PMID- 22632894
TI  - SOD1, but not SOD3, deficiency accelerates diabetic renal injury in C57BL/6
      Ins2(Akita) diabetic mice.
AB  - Superoxide dismutase (SOD) is a major defender against excessive superoxide
      generated under hyperglycemia. We have recently reported that renal SOD1
      (cytosolic CuZn-SOD) and SOD3 (extracellular CuZn-SOD) isoenzymes are remarkably
      down-regulated in KK/Ta-Ins2(Akita) diabetic mice, which exhibit progressive
      diabetic nephropathy (DN), but not in DN-resistant C57BL/6- Ins2(Akita) (C57BL/6
      Akita) diabetic mice. To determine the role of SOD1 and SOD3 in DN, we generated
      C57BL/6-Akita diabetic mice with deficiency of SOD1 and/or SOD3 and investigated
      their renal phenotype at the age of 20 weeks. Increased glomerular superoxide
      levels were observed in SOD1(-/-)SOD3(+/+) and SOD1(-/-)SOD3(-/-) C57BL/6-Akita
      mice but not in SOD1(+/+)SOD3(-/-) C57BL/6-Akita mice. The SOD1(-/-)SOD3(+/+) and
      SOD1(-/-)SOD3(-/-) C57BL/6-Akita mice exhibited higher glomerular filtration
      rate, increased urinary albumin levels, and advanced mesangial expansion as
      compared with SOD1(+/+)SOD3(+/+) C57BL/6-Akita mice, yet the severity of DN did
      not differ between the SOD1(-/-)SOD3(+/+) and SOD1(-/-)SOD3(-/-) C57BL/6-Akita
      groups. Increased renal mRNA expression of transforming growth factor-beta1 (TGF
      beta1) and connective tissue growth factor (CTGF), reduced glomerular nitric
      oxide (NO), and increased renal prostaglandin E2 (PGE2) production were noted in
      the SOD1(-/-)SOD3(+/+) and SOD1(-/-)SOD3(-/-) C57BL/6-Akita mice. This finding
      indicates that such renal changes in fibrogenic cytokines, NO, and PGE2, possibly
      caused by superoxide excess, would contribute to the development of overt
      albuminuria by promoting mesangial expansion, endothelial dysfunction, and
      glomerular hyperfiltration. The present results demonstrate that deficiency of
      SOD1, but not SOD3, increases renal superoxide in the setting of diabetes and
      causes overt renal injury in nephropathy-resistant diabetic mice, and that SOD3
      deficiency does not provide additive effects on the severity of DN in SOD1
      deficient C57BL/6-Akita mice.

PMID- 22632896
TI  - Long-term outcome of a consecutive series of subscapularis tendon tears repaired
      arthroscopically.
AB  - PURPOSE: The purpose of this study was to evaluate the long-term outcome of
      arthroscopic repair of subscapularis tendon tears. METHODS: A retrospective
      review was performed of subscapularis tendon tears treated with an arthroscopic
      technique from 1999 to 2003. Revision repairs and open repairs were excluded. The
      minimum follow-up was 7 years. Postoperative functional outcome was determined by
      University of California, Los Angeles and American Shoulder and Elbow Surgeons
      scores. RESULTS: Seventy-nine patients with a mean age of 60.8 years at the time
      of surgery were available for follow-up at a mean of 104.7 months. Mean
      University of California, Los Angeles scores improved from 16.5 preoperatively to
      30.1 postoperatively (P < .001), and mean American Shoulder and Elbow Surgeons
      scores improved from 40.8 preoperatively to 88.5 postoperatively (P < .001).
      Results were rated as good or excellent in 83.3% of cases, 92.4% of patients
      returned to normal activities, and 92.4% of patients were satisfied. CONCLUSIONS:
      Arthroscopic rotator cuff repair that includes repair of the subscapularis tendon
      can lead to good or excellent results in most cases. This study shows that
      improvement in functional outcome after arthroscopic repair of a subscapularis
      tendon tear is maintained long-term. LEVEL OF EVIDENCE: Level IV, therapeutic
      case series.

PMID- 22632898
TI  - Preparation of clinical-scale 99Mo/99mTc column generator using neutron activated
      low specific activity 99Mo and nanocrystalline gamma-Al2O3 as column matrix.
AB  - INTRODUCTION: Preparation of clinical-scale (99)Mo/(99m)Tc generator using
      (n,gamma) activated low specific activity (99)Mo and nanocrystalline gamma
      Al(2)O(3) as a high capacity sorbent matrix is attempted. METHODS:
      Nanocrystalline gamma-Al(2)O(3) was synthesized by 'solid state mechanochemical'
      reaction of aluminum nitrate with ammonium bicarbonate. Experimental parameters
      were optimized to effectively separate (99m)Tc from (99)Mo using this sorbent as
      the column matrix. The performance features of a 13 GBq (350 mCi) (99)Mo/(99m)Tc
      generator using this sorbent and (99)Mo produced by (n,gamma) route having
      specific activity 12.9-18.5 GBq/g were evaluated for 10 days. RESULTS: The
      sorbent possessed the requisite selectivity for (99)Mo and demonstrated a maximum
      sorption capacity of 200 +/- 5mg Mo/g, which is ~10 times higher than that of
      ordinary acidic alumina. The overall yield of (99m)Tc was >80%, with
      radionuclidic purity >99.99% and radiochemical purity >99%. The yield of (99m)Tc
      varied from 7.8 to 2.1 GBq in the eluate for the six days of operation of the
      generator. The radioactive concentration of (99m)Tc eluted was adequate for the
      formulation of radiopharmaceuticals. The performance of the generator remained
      consistent over an extended period of 10 days. The eluted (99m)Tc was suitable
      for the formulation of (99m)Tc-DMSA and (99m)Tc-EC resulting in high
      radiolabeling yields (>98%). CONCLUSION: The effectiveness of gamma-Al(2)O(3) as
      a new generation sorbent in the development of clinically useful (99)Mo/(99m)Tc
      generator using low specific activity (99)Mo and yielding (99m)Tc with adequate
      radioactive concentration and high purity suitable for formulation of
      radiopharmaceuticals is demonstrated.

PMID- 22632897
TI  - Akt3 deficiency in macrophages promotes foam cell formation and atherosclerosis
      in mice.
AB  - Akt, a serine-threonine protein kinase, exists as three isoforms. The Akt
      signaling pathway controls multiple cellular functions in the cardiovascular
      system, and the atheroprotective endothelial cell-dependent role of Akt1 has been
      recently demonstrated. The role of Akt3 isoform in cardiovascular pathophysiology
      is not known. We explored the role of Akt3 in atherosclerosis using mice with a
      genetic ablation of the Akt3 gene. Using hyperlipidemic ApoE(-/-) mice, we
      demonstrated a macrophage-dependent, atheroprotective role for Akt3. In vitro
      experiments demonstrated differential subcellular localization of Akt1 and Akt3
      in macrophages and showed that Akt3 specifically inhibits macrophage cholesteryl
      ester accumulation and foam cell formation, a critical early event in
      atherogenesis. Mechanistically, Akt3 suppresses foam cell formation by reducing
      lipoprotein uptake and promoting ACAT-1 degradation via the ubiquitin-proteasome
      pathway. These studies demonstrate the nonredundant atheroprotective role for
      Akt3 exerted via the previously unknown link between the Akt signaling pathway
      and cholesterol metabolism.

PMID- 22632899
TI  - Nucleofection of a DNA vaccine into human monocyte-derived dendritic cells.
AB  - An efficient method for delivering DNA vaccines into dendritic cells is
      considered to be of paramount importance. Electroporation-based technology
      (nucleofection) has gained increasingly popularity, but few reports focused on
      the possible functional consequences related to this method. In this study, the
      nucleofection technique was used to transfer the recombinant plasmid into hMoDCs
      for phenotype expression analysis and immunopotency detection. The results showed
      that the nucleofection of increasing concentrations of plasmid DNA decreased the
      viability of the hMoDCs. The welfare of nucleofected hMoDCs depended on the
      dosage of the plasmid and the plasmid's retention time within the cells.
      Accompanied by the process of nucleofection, it would bring some non-specific
      changes. The methodology reported here is suggestive of a feasible system for DNA
      vaccine transfer into hMoDCs with the caution of certain undesired effect.

PMID- 22632900
TI  - A national study of individuals who handle migratory birds for evidence of avian
      and swine-origin influenza virus infections.
AB  - BACKGROUND: Persons with occupational or recreational exposure to migratory birds
      may be at risk for infection with highly pathogenic avian influenza and other
      avian influenza viruses since wild birds are the natural reservoir of influenza
      A. Additionally, bird handlers may host avian and swine-origin influenza (pH1N1)
      virus co-infections, which generate reassortant viruses with high pathogenicity
      in mammals. OBJECTIVES: We assessed the prevalence of avian and swine influenza
      viruses in US-based bird handlers and estimated their exposure to different
      orders of wild birds including waterfowl (Anseriformes), songbirds
      (Passeriformes), and shorebirds (Charadriiformes). STUDY DESIGN: Cross-sectional
      serologic survey accompanied by a questionnaire to estimate behavioral risk
      factors. This is first survey of US-based bird handlers who also work at
      international sites. RESULTS: 401 participants were recruited and tested over the
      course of 3 years. One participant with occupational exposure to migratory birds
      had evidence of past infections with a H5N2 virus antigenically related to
      A/Nopi/MN/07/462960-02, which is the first case of this influenza subtype in a
      human host associated with exposure to wild rather than domestic birds. We
      detected no avian and swine-origin influenza virus co-infections. The exposure of
      bird handlers to songbirds was four times greater than to shorebirds or
      waterfowl. CONCLUSIONS: Though rare, the transmission of avian influenza viruses
      from migratory birds to US-based bird handlers has potentially significant public
      health and economic consequences.

PMID- 22632901
TI  - Enhanced detection of Rift Valley fever virus using molecular assays on whole
      blood samples.
AB  - BACKGROUND: Rift Valley fever (RVF) is an emerging arthropod-borne zoonoses of
      global agricultural and public health importance. In December 2006, an RVF
      outbreak was recognized in Kenya which led to the deployment of international
      response laboratory teams to the area. OBJECTIVES: A field laboratory was
      operated in Malindi, Kenya to provide safe sample handling and molecular testing
      for RVF virus (RVFV) as well as selected other pathogens for differential
      diagnosis. STUDY DESIGN: Safe sample handling was carried out using a negative
      pressure flexible film isolator (glovebox) and commercial reagents to inactivate
      clinical specimens and purify nucleic acid. Whole blood was routinely used for
      diagnostic testing although paired plasma samples were also tested in select
      cases. Subsequently, human macrophages were tested in vitro for their
      susceptibility to RVFV. RESULTS: The field laboratory received samples from 33
      individuals and a definite laboratory diagnosis was provided in 16 of these
      cases. Using molecular diagnostic techniques, RVFV was more consistently detected
      in whole blood than in plasma samples most likely due to association of RVFV with
      blood cells. Subsequent in vitro studies identified macrophages as a target cell
      for RVFV replication. CONCLUSIONS: RVFV appears to replicate in blood cells such
      as macrophages. Thus, the sensitivity of molecular diagnostic testing is improved
      if whole blood is used as the clinical specimen rather than plasma or serum.

PMID- 22632902
TI  - Sex differences in sub-clinical psychosis--results from a community study over 30
      years.
AB  - Sex differences in schizophrenia have long been reported. They are found within
      almost all aspects of the disease, from incidence and prevalence, age of onset,
      symptomatology, and course to its psycho-social outcome. Many sex-related
      hypotheses have been developed about the biology, psychology, or sociology of
      that disease. A further approach to study sex differences would be to examine
      such differences in sub-clinical psychotic states as well. If factors related to
      full-blown psychosis were equally meaningful over the entire psychosis continuum,
      we should expect that "true" sex differences could also be identified in sub
      clinical psychosis. Here, we studied sex differences in sub-clinical psychosis
      within a community cohort in Zurich, Switzerland. This population was followed
      for over 30 years and included males and females between the ages of 20/21 and
      49/50. We applied two different measures of sub-clinical psychosis representing
      schizotypal signs and schizophrenia nuclear symptoms. Using cross-sectional and
      longitudinal analyses, we found no significant sex differences in sub-clinical
      psychosis over time with respect to age of onset, symptomatology, course, or
      psycho-social outcome. Thus it appears that sex differences in psychosis manifest
      themselves at the high end of the continuum (full-blown schizophrenia) rather
      than within the sub-threshold range. Possibly males and females have separate
      thresholds for certain symptoms because they are differently vulnerable or
      exposed to various risk factors.

PMID- 22632903
TI  - Association between unemployment, income, education level, population size and
      air pollution in Czech cities: evidence for environmental inequality? A pilot
      national scale analysis.
AB  - We analyzed differentials in exposure to SO(2), PM(10) and NO(2) among Czech
      urban populations categorized according to education level, unemployment rate,
      population size and average annual salary. Altogether 39 cities were included in
      the analysis. The principal component analysis revealed two factors explaining
      72.8% of the data variability. The first factor explaining 44.7% of the data
      variability included SO(2), PM(10), low education level and high unemployment,
      documenting that inhabitants with unfavorable socioeconomic status mainly reside
      in smaller cities with higher concentration levels of combustion-related air
      pollutants. The second factor explaining 28.1% of the data variability included
      NO(2), high salary, high education level and large population, suggesting that
      large cities with residents with higher socioeconomic status are exposed to
      higher levels of traffic-related air pollution. We conclude that, after more than
      a decade of free-market economy, the Czech Republic, a former Soviet satellite
      with a centrally planned economy, displays signs of a certain kind of
      environmental inequality, since environmental hazards are unevenly distributed
      among the Czech urban populations.

PMID- 22632904
TI  - [Advanced dorsolumbar psoriasis: regional or general anaesthesia?].

PMID- 22632905
TI  - [Massive obstetric haemorrhage in a patient with placenta percreta].
AB  - We present a case of a 38 year-old patient with prenatal diagnosis of placenta
      praevia. When the elective caesarean began it was found a placenta accreta. In
      spite of an emergency hysterectomy, embolisation using interventional radiography
      was needed after a massive obstetric haemorrhage. The post-operative period
      progressed without incidents.

PMID- 22632906
TI  - rt-PA for ischaemic stroke: what will the next question be?

PMID- 22632907
TI  - Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated
      systematic review and meta-analysis.
AB  - BACKGROUND: Recombinant tissue plasminogen activator (rt-PA, alteplase) improved
      functional outcome in patients treated soon after acute ischaemic stroke in
      randomised trials, but licensing is restrictive and use varies widely. The IST-3
      trial adds substantial new data. We therefore assessed all the evidence from
      randomised trials for rt-PA in acute ischaemic stroke in an updated systematic
      review and meta-analysis. METHODS: We searched for randomised trials of
      intravenous rt-PA versus control given within 6 h of onset of acute ischaemic
      stroke up to March 30, 2012. We estimated summary odds ratios (ORs) and 95% CI in
      the primary analysis for prespecified outcomes within 7 days and at the final
      follow-up of all patients treated up to 6 h after stroke. FINDINGS: In up to 12
      trials (7012 patients), rt-PA given within 6 h of stroke significantly increased
      the odds of being alive and independent (modified Rankin Scale, mRS 0-2) at final
      follow-up (1611/3483 [46.3%] vs 1434/3404 [42.1%], OR 1.17, 95% CI 1.06-1.29;
      p=0.001), absolute increase of 42 (19-66) per 1000 people treated, and favourable
      outcome (mRS 0-1) absolute increase of 55 (95% CI 33-77) per 1000. The benefit of
      rt-PA was greatest in patients treated within 3 h (mRS 0-2, 365/896 [40.7%] vs
      280/883 [31.7%], 1.53, 1.26-1.86, p<0.0001), absolute benefit of 90 (46-135) per
      1000 people treated, and mRS 0-1 (283/896 [31.6%] vs 202/883 [22.9%], 1.61, 1.30
      1.90; p<0.0001), absolute benefit 87 (46-128) per 1000 treated. Numbers of deaths
      within 7 days were increased (250/2807 [8.9%] vs 174/2728 [6.4%], 1.44, 1.18
      1.76; p=0.0003), but by final follow-up the excess was no longer significant
      (679/3548 [19.1%] vs 640/3464 [18.5%], 1.06, 0.94-1.20; p=0.33). Symptomatic
      intracranial haemorrhage (272/3548 [7.7%] vs 63/3463 [1.8%], 3.72, 2.98-4.64;
      p<0.0001) accounted for most of the early excess deaths. Patients older than 80
      years achieved similar benefit to those aged 80 years or younger, particularly
      when treated early. INTERPRETATION: The evidence indicates that intravenous rt-PA
      increased the proportion of patients who were alive with favourable outcome and
      alive and independent at final follow-up. The data strengthen previous evidence
      to treat patients as early as possible after acute ischaemic stroke, although
      some patients might benefit up to 6 h after stroke. FUNDING: UK Medical Research
      Council, Stroke Association, University of Edinburgh, National Health Service
      Health Technology Assessment Programme, Swedish Heart-Lung Fund, AFA Insurances
      Stockholm (Arbetsmarknadens Partners Forsakringsbolag), Karolinska Institute,
      Marianne and Marcus Wallenberg Foundation, Research Council of Norway, Oslo
      University Hospital.

PMID- 22632909
TI  - Impact of trauma center designation on outcomes: is there a difference between
      Level I and Level II trauma centers?
AB  - BACKGROUND: Within organized trauma systems, both Level I and Level II trauma
      centers are expected to have the resources to treat patients with major
      multisystem trauma. The evidence supporting separate designations for Level I and
      Level II trauma centers is inconclusive. The objective of this study was to
      compare mortality and complications for injured patients admitted to Level I and
      Level II trauma centers. STUDY DESIGN: Using data from the Pennsylvania Trauma
      Outcomes Study registry, we performed a retrospective observational study of
      208,866 patients admitted to 28 Level I and Level II trauma centers between 2000
      and 2009. Regression modeling was used to estimate the association between
      patient outcomes and trauma center designation, after controlling for injury
      severity, mechanism of injury, transfer status, and physiology. RESULTS: Patients
      admitted to Level I trauma centers had a 15% lower odds of mortality (adjusted
      odds ratio [adj OR] 0.85; 95% CI 0.72 to 0.99) and a 35% increased odds of
      complications (adj OR 1.37; 95% CI 1.04 to 1.79). The survival benefit associated
      with admission to Level I centers was strongest in patients with very severe
      injuries (Injury Severity Score [ISS] >= 25; adj OR 0.78; 95% CI 0.64 to 0.95).
      Less severely injured patients with an ISS < 9 (adj OR 0.91; 95% CI 0.64 to 1.30)
      and with an ISS between 9 and 15 (adj OR 0.98; 95% CI 0.81 to 1.18) had similar
      risks of mortality in Level I and Level II trauma centers. CONCLUSIONS: Severely
      injured patients admitted to Level I trauma centers have a lower risk of
      mortality compared with patients admitted to Level II centers. These findings
      support the continuation of a 2-tiered designation system for trauma.

PMID- 22632910
TI  - Laparoscopic distal pancreatectomy: trends and lessons learned through an 11-year
      experience.
AB  - BACKGROUND: As compared with open distal pancreatectomy, laparoscopic distal
      pancreatectomy (LDP) is associated with lower morbidity and shorter hospital
      stays. Existing reports do not elucidate trends in patient selection, technique,
      and outcomes over time. We aimed to determine outcomes after LDP at a specialized
      center, analyze trends of patient selection and operative technique, and validate
      a complication risk score (CRS). STUDY DESIGN: Patients undergoing LDP between
      January 2000 and January 2011 were identified and divided into 2 equal groups to
      represent our early and recent experiences. Demographics, tumor characteristics,
      operative technique, and perioperative outcomes were examined and compared
      between groups. A CRS was calculated for the entire cohort and examined against
      observed outcomes. RESULTS: A total of 132 LDPs were attempted, of which 8 (6.1%)
      were converted to open procedures. Thirty-day overall and major complication
      rates were 43.2% and 12.9%, respectively, with mortality < 1%. Pancreatic
      fistulas occurred in 28 (21%) patients, of which 14 (11%) were clinically
      significant. Recent LDPs (n = 66) included patients with increasingly severe
      comorbidities (Charlson scores > 2, 40.9% vs 16.7%, p = 0.003), more proximal
      tumors (74.2% vs 26.2%, p < 0.001), more extended resections (10.6 vs 8.3 cm, p <
      0.001), shorter operative times (141 vs 172 minutes, p = 0.007), and less
      frequent use of a hand port (25.8% vs 66.6%, p < 0.001). No significant
      differences were found in perioperative outcomes between the groups. As compared
      with the hand access technique, the total laparoscopic approach was associated
      with shorter hospital stays (5.3 vs 6.8 days, p = 0.032). Increasing CRS was
      associated with longer operative time, significant fistulas, wound infections,
      blood transfusions, major complications, ICU readmissions, and
      rehospitalizations. CONCLUSIONS: This large, single-institution series
      demonstrates that despite a shift in patient selection to sicker patients with
      more proximal tumors, similar perioperative outcomes can be achieved with
      laparoscopic distal pancreatectomy. The CRS appears to be a reliable preoperative
      assessment tool for assessing other adverse perioperative outcomes in addition to
      predicting overall complications and fistulas as originally published.

PMID- 22632912
TI  - Implementation of a surgical comprehensive unit-based safety program to reduce
      surgical site infections.
AB  - BACKGROUND: Surgical site infections (SSI) are a common and costly problem,
      prolonging hospitalization and increasing readmission. Adherence to well-known
      infection control process measures has not been associated with substantial
      reductions in SSI. To date, the global burden of preventable SSI continues to
      result in patient harm and increased health care costs on a broad scale. STUDY
      DESIGN: We designed a study to evaluate the association between implementation of
      a surgery-based comprehensive unit-based safety program (CUSP) and postoperative
      SSI rates. One year of pre- and post-CUSP intervention SSI rates were collected
      using the high-risk pilot module of the American College of Surgeons National
      Surgical Quality Improvement Program (July 2009 to July 2011). The CUSP group met
      monthly and consisted of a multidisciplinary team of front-line providers (eg,
      surgeons, nurses, operating room technicians, and anesthesiologists) who were
      directly involved in the care of colorectal surgery patients. Surgical Care
      Improvement Project process measure compliance was monitored using standard
      methods from the Centers for Medicare and Medicaid Services. RESULTS: In the 12
      months before implementation of the CUSP and interventions, the mean SSI rate was
      27.3% (76 of 278 patients). After commencement of interventions, the rate was
      18.2% (59 of 324 patients) for the subsequent 12 months--a 33.3% decrease (95%
      CI, 9-58%; p < 0.05). The interventions included standardization of skin
      preparation; administration of preoperative chlorhexidine showers; selective
      elimination of mechanical bowel preparation; warming of patients in the
      preanesthesia area; adoption of enhanced sterile techniques for skin and fascial
      closure; addressing previously unrecognized lapses in antibiotic prophylaxis.
      There was no difference in surgical process measure compliance as measured by the
      Surgical Care Improvement Project during the same time period. CONCLUSIONS:
      Formation of small groups of front-line providers to address patient harm using
      local wisdom and existing evidence can improve patient safety. We demonstrate a
      surgery-based CUSP intervention that might have markedly decreased SSI in a high
      risk population.

PMID- 22632911
TI  - Effect of introducing hematoma ultrasound-guided lumpectomy in a surgical
      practice.
AB  - BACKGROUND: Preoperative needle localization (NL) is the gold standard for
      lumpectomy of nonpalpable breast cancer. Hematoma ultrasound-guided (HUG)
      lumpectomy can offer several advantages. The purpose of this study was to compare
      the use of HUG with NL lumpectomy in a single surgical practice. STUDY DESIGN:
      Patients with nonpalpable lesions who underwent NL or HUG lumpectomy from January
      2007 to December 2009 by a single surgeon were identified from a breast surgery
      database. Ease of scheduling, volume excised, re-excision rates, operating room
      time, and health care charges were the main outcomes variables. Univariate and
      multivariate analyses were performed to compare the 2 groups. RESULTS: Lumpectomy
      was performed in 110 patients, 55 underwent HUG and 55 underwent NL. Hematoma
      ultrasound-guided lumpectomy was associated with a nearly 3-fold increase in the
      odds ratio of additional tissue being submitted to pathology (p = 0.039), but
      neither the total amount of breast tissue removed, nor the need for second
      procedure were statistically different between the 2 groups. Duration of the
      surgical procedure did not vary between the 2 groups; however, the time from
      biopsy to surgery was shorter for HUG by an expected 9.7 days (p = 0.019),
      implying greater ease of scheduling. Mean charges averaged $250 less for HUG than
      for NL, but this difference was not statistically significant. CONCLUSIONS:
      Hematoma ultrasound-guided is equivalent to NL with regard to volume of tissue
      excised, need for operative re-excision, and operating room time. Adoption of HUG
      in our practice allowed for more timely surgical care.

PMID- 22632913
TI  - Laparoscopic vs open appendectomy in obese patients: outcomes using the American
      College of Surgeons National Surgical Quality Improvement Program database.
AB  - BACKGROUND: Although open and laparoscopic appendectomies are comparable
      operations in terms of outcomes, it is unknown whether this is true in the obese
      patient. Our objective was to compare short-term outcomes in obese patients after
      laparoscopic vs open appendectomy. STUDY DESIGN: Using the American College of
      Surgeons National Surgical Quality Improvement Program database (2005-2009),
      13,330 obese patients (body mass index >= 30) who underwent an appendectomy were
      identified (78% laparoscopic, 22% open). The association between surgical
      approach (laparoscopic vs open) and outcomes was first evaluated using
      multivariable logistic regression. Next, to minimize the influence of treatment
      selection bias, we created a 1:1 matched cohort using all 41 of the preoperative
      covariates in the National Surgical Quality Improvement Program database.
      Reanalysis was then performed with the unmatched patients excluded. Main outcomes
      measures included patient morbidity and mortality, operating room return,
      operative times, and hospital length of stay. RESULTS: Laparoscopic appendectomy
      was associated with a 57% reduction in overall morbidity in all the obese
      patients after the multivariable risk-adjusted analysis (odds ratio = 0.43; 95%
      CI, 0.36-0.52; p < 0.0001), and a 53% reduction in risk in the matched cohort
      analysis (odds ratio = 0.47; 95% CI, 0.32-0.65; p < 0.0001). Mortality rates were
      the same. In the matched cohort, length of stay was 1.2 days shorter for obese
      patients undergoing laparoscopic appendectomy compared with open appendectomy
      (mean difference 1.2 days; 95% CI, 0.98-1.42). CONCLUSIONS: In obese patients,
      laparoscopic appendectomy had superior clinical outcomes compared with open
      appendectomy after accounting for preoperative risk factors.

PMID- 22632915
TI  - A lesson on maturing in surgery from Dr DeBakey.

PMID- 22632914
TI  - Duty hours, quality of care, and patient safety: general surgery resident
      perceptions.
AB  - BACKGROUND: The balance between patient treatment risks and training residents to
      proficiency is confounded by duty-hour limits. Stricter limits have been
      recommended to enhance quality and safety, although supporting data are scarce.
      STUDY DESIGN: A previously piloted survey was delivered with the 2010 American
      Board of Surgery In-Training Examination (ABSITE). First postgraduate year (PGY1)
      and PGY2 trainees took the Junior examination (IJE); PGY3 and above took the
      Senior examination (ISE). Residency type, size, and location were linked to
      examinees using program codes. Five survey items queried all residents about the
      impact of further hour limits on care quality; online test residents answered 7
      more items probing medical error sources. Data were analyzed using factorial
      ANOVA for association with sex, PGY level, and program demographics. RESULTS:
      There were 6,161 categorical surgery residents who took the ABSITE: 60% men, 60%
      ISE, and two-thirds in university programs. Paper (n = 5,079) and online (n =
      1,082) examinees were similar. Item response rates ranged from 91% to 98%. Few
      (<25%) perceived that stricter hour limits would improve care quality to a large
      or maximal extent. IJE plus West and Northeast residents significantly more often
      favored fewer hours. Factors perceived as contributing to medical errors usually
      or always by >= 15% of residents were incomplete handoffs, inexperience or lack
      of knowledge, insufficient ancillary personnel, and excessive workload.
      CONCLUSIONS: Most categorical surgery residents do not perceive that reduced duty
      hours will noticeably improve quality of care. Resident perceptions of causes of
      medical errors suggest that system changes are more likely to enhance patient
      safety than further hour limits.

PMID- 22632916
TI  - Can hospitals "game the system" by avoiding high-risk patients?
AB  - BACKGROUND: It has been suggested that implementation of quality-improvement
      benchmarking programs can lead to risk-avoidance behaviors in some physicians and
      hospitals in an attempt to improve their rankings, potentially denying patients
      needed treatment. We hypothesize that avoidance of high-risk patients will not
      change risk-adjusted rankings. STUDY DESIGN: We conducted a simulation analysis
      of 6 complex operations in the Nationwide Inpatient Sample, including abdominal
      aortic aneurysm repair, aortic valve replacement, coronary artery bypass
      grafting, percutaneous coronary intervention, esophagectomy, and pancreatic
      resection. Primary outcomes included in-hospital mortality. Hospitals were ranked
      into quintiles based on observed-to-expected (O/E) mortality ratios, with their
      expected mortalities calculated based on models generated from the previous 3
      years. Half of the hospitals were then randomly selected to undergo risk
      avoidance by avoiding 25% of patients with higher than median risks (ie,
      Charlson, Elixhauser, age, minority, or uninsured status). Their new O/E ratios
      and hospital-rank categories were compared with their original values. RESULTS: A
      total of 2,235,298 patients were analyzed, with an overall observed mortality
      rate of 1.9%. Median change in O/E ratios across all simulations was zero, and
      O/E ratios did not change in 97.5% to 99.3% of the hospitals, depending on the
      risk definitions. Additionally, 70.5% to 98.0% of hospital rankings remained
      unchanged, 1.3% to 13.1% of hospital rankings improved, and 0.7% to 14.3% of
      hospital rankings worsened after risk avoidance. CONCLUSIONS: Risk-adjusted
      rankings of hospitals likely cannot be changed by simply avoiding high-risk
      patients. In the minority of scenarios in which risk-adjusted rankings changed,
      they were as likely to improve as worsen after risk avoidance.

PMID- 22632917
TI  - Fluorescence-guided surgery allows for more complete resection of pancreatic
      cancer, resulting in longer disease-free survival compared with standard surgery
      in orthotopic mouse models.
AB  - BACKGROUND: Negative surgical margins are vital to achieve cure and prolong
      survival in patients with pancreatic cancer. We inquired if fluorescence-guided
      surgery (FGS) could improve surgical outcomes and reduce recurrence rates in
      orthotopic mouse models of human pancreatic cancer. STUDY DESIGN: A randomized
      active-control preclinical trial comparing bright light surgery (BLS) to FGS was
      used. Orthotopic mouse models of human pancreatic cancer were established using
      the BxPC-3 pancreatic cancer cell line expressing red fluorescent protein (RFP).
      Two weeks after orthotopic implantation, tumors were resected with BLS or FGS.
      Pre- and postoperative images were obtained with the OV-100 Small Animal Imaging
      System to assess completeness of surgical resection in real time.
      Postoperatively, noninvasive whole body imaging was done to assess recurrence and
      follow tumor progression. Six weeks postoperatively, mice were sacrificed to
      evaluate primary pancreatic and metastatic tumor burden at autopsy. RESULTS: A
      more complete resection of pancreatic cancer was achieved using FGS compared with
      BLS: 98.9% vs 77.1%, p = 0.005. The majority of mice undergoing BLS (63.2%) had
      evidence of gross disease with no complete resections; 20% of mice undergoing FGS
      had complete resection and an additional 75% had only minimal residual disease (p
      = 0.0001). The mean postoperative tumor burden was significantly less with FGS
      compared with BLS: 0.08 +/- 0.06 mm(2) vs 2.64 +/- 0.63 mm(2), p = 0.001. The
      primary tumor burden at termination was significantly less with FGS compared with
      BLS: 19.3 +/- 5.3 mm(2) vs 6.2 +/- 3.6 mm(2), p = 0.048. FGS resulted in
      significantly longer disease-free survival than BLS (p = 0.02, hazard ratio =
      0.39, 95% CI 0.17, 0.88). CONCLUSIONS: Surgical outcomes were improved in
      pancreatic cancer using fluorescence-guidance. This novel approach has
      significant potential to improve surgical treatment of cancer.

PMID- 22632918
TI  - Ambulatory arterial stiffness index: a systematic review and meta-analysis.
AB  - OBJECTIVE: The dynamic relationship between 24 h diastolic and systolic
      ambulatory blood pressure (BP) expressed by the ambulatory arterial stiffness
      index (AASI) has been introduced as a novel measure of arterial function, which
      independently predicts cardiovascular mortality. This article reviews the
      published evidence on the features and the clinical relevance of AASI. METHODS: A
      systematic review and meta-analysis of the evidence on AASI from 51 cross
      sectional and longitudinal studies in adults was conducted. RESULTS: Studies of
      the reproducibility of AASI have shown a mean difference between assessments at
      0.014 (95% CI -0.001, 0.028; 3 studies, n = 451) and repeatability coefficients
      ranging from 0.24 to 0.40. AASI appears to be independently associated with age,
      systolic BP and pulse pressure, and inversely with the nocturnal systolic and
      diastolic BP decline. A moderate pooled association of AASI with 24 h pulse
      pressure (pooled correlation coefficient r 0.47, 95% CI 0.40, 0.54; 20 studies, n
      = 29,186) and pulse wave velocity (pooled r 0.30, 95% CI 0.19, 0.42; 9 studies, n
      = 4123) was demonstrated, as well as with other measures of arterial function and
      target-organ damage. The adjusted pooled hazard ratio for stroke corresponding to
      a study-specific one standard deviation increase in AASI was 1.26 (95% CI 1.08,
      1.45; 3 studies, n = 14,320). CONCLUSIONS: The available evidence suggests that
      AASI, obtained by ambulatory BP monitoring, predicts future cardiovascular
      events, particularly stroke, and is associated with indices of arterial function.
      The precise pathophysiological mechanisms remain obscure. Research is required to
      determine the usefulness of AASI as a therapeutic target in clinical practice.

PMID- 22632919
TI  - 25-Hydroxyvitamin D is lower in deprived groups, but is not associated with
      carotid intima media thickness or plaques: results from pSoBid.
AB  - OBJECTIVE: The association of the circulating serum vitamin D metabolite 25
      hydroxyvitamin D (25OHD) with atherosclerotic burden is unclear, with previous
      studies reporting disparate results. METHOD: Psychological, social and biological
      determinants of ill health (pSoBid) is a study of participants aged 35-64 years
      from Glasgow who live at extremes of the socioeconomic spectrum. Vitamin D
      deficiency was defined as 25OHD < 25nmol/L, as per convention. Cross-sectional
      associations between circulating 25OHD concentrations and a range of
      socioeconomic, lifestyle, and biochemistry factors, as well as carotid intima
      media thickness (cIMT) and plaque presence were assessed in 625 participants.
      RESULTS: Geometric mean levels of circulating 25OHD were higher among the least
      deprived (45.6 nmol/L, 1-SD range 24.4-85.5) versus most deprived (34.2 nmol/L, 1
      SD range 16.9-69.2; p < 0.0001). In the least deprived group 15% were "deficient"
      in circulating 25OHD versus 30.8% in the most deprived (chi(2)p < 0.0001). Log
      25OHD was 27% lower among smokers (p < 0.0001), 20% higher among the physically
      active versus inactive (p = 0.01), 2% lower per 1 kg/m(2) increase in body mass
      index (BMI) (p < 0.0001), and showed expected seasonal variation (chi(2)p <
      0.0001). Log 25OHD was 13% lower in the most versus least deprived independent of
      the aforementioned lifestyle confounding factors (p = 0.03). One unit increase in
      log 25OHD was not associated with atherosclerotic burden in univariable models;
      cIMT (effect estimate 0.000 mm [95% CI -0.011, 0.012]); plaque presence (OR 0.88
      [0.75, 1.03]), or in multivariable models. CONCLUSION: There is no strong
      association of 25OHD with cIMT or plaque presence, despite strong evidence 25OHD
      associates with lifestyle factors and socioeconomic deprivation.

PMID- 22632921
TI  - Ultrasound and radiology surrogate endpoints in pharmacological studies.
AB  - Cardiovascular studies investigating therapeutic intervention with clinical
      endpoints are costly due to the need for considerable duration and large number
      of patients, or both. Therefore, for evaluation of novel cardiovascular drug
      efficacy, surrogate endpoints are used. Cardiovascular imaging endpoints have
      proven their worth. Sometimes the relevance of imaging is questioned and other
      methods are suggested instead. There is also some confusion about the strengths
      of imaging endpoints. The aim of the present paper is to review ultrasound and
      radiology imaging techniques as surrogate endpoints in pharmacological trials.

PMID- 22632922
TI  - Alternating verbal fluency performance following bilateral subthalamic nucleus
      deep brain stimulation for Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Despite common occurrences of verbal fluency declines
      following bilateral subthalamic nucleus deep brain stimulation (STN-DBS) for the
      treatment of Parkinson's disease (PD), alternating fluency measures using cued
      and uncued paradigms have not been evaluated. METHODS: Twenty-three STN-DBS
      patients were compared with 20 non-surgical PD patients on a comprehensive
      neuropsychological assessment, including cued and uncued intradimensional
      (phonemic/phonemic and semantic/semantic) and extradimensional
      (phonemic/semantic) alternating fluency measures at baseline and 6-month follow
      up. RESULTS: STN-DBS patients demonstrated a greater decline on the cued
      phonemic/phonemic fluency and the uncued phonemic/semantic fluency tasks compared
      to the PD patients. For STN-DBS patients, verbal learning and information
      processing speed accounted for a significant proportion of the variance in
      declines in alternating phonemic/phonemic and phonemic/semantic fluency scores,
      respectively, whilst only naming was related to uncued phonemic/semantic
      performance for the PD patients. Both groups were aided by cueing for the
      extradimensional task at baseline and follow-up, and the PD patients were also
      aided by cueing for the phonemic/phonemic task on follow-up. CONCLUSIONS: These
      findings suggest that changes in alternating fluency are not related to disease
      progression alone as STN-DBS patients demonstrated greater declines over time
      than the PD patients, and this change was related to declines in information
      processing speed.

PMID- 22632920
TI  - Apo E4 and lipoprotein-associated phospholipase A2 synergistically increase
      cardiovascular risk.
AB  - OBJECTIVE: Apolipoprotein E (apoE) has been implicated as conveying increased
      risk for coronary artery disease (CAD). Previous studies suggest a role of apoE
      as a modulator of immune response and inflammatory properties. We hypothesized
      that the presence of apo E4 is associated with an increased inflammatory burden
      in subjects with CAD as compared to subjects without CAD. METHODS: ApoE
      genotypes, systemic (C-reactive protein [CRP], fibrinogen, serum amyloid-A [SAA])
      and vascular inflammatory markers (Lipoprotein-associated phospholipase A(2) [Lp
      PLA(2)] and pentraxin-3 [PTX-3]) were assessed in 324 Caucasians and 208 African
      Americans, undergoing coronary angiography. RESULTS: For both ethnic groups, Lp
      PLA(2) index, an integrated measure of Lp-PLA(2) mass and activity, increased
      significantly and stepwise across apoE isoforms (P = 0.009 and P = 0.026 for
      African Americans and Caucasians respectively). No differences were found for
      other inflammatory markers tested (CRP, fibrinogen, SAA and PTX-3). For the top
      cardiovascular score tertile, apo E4 carriers had a significantly higher level of
      Lp-PLA(2) index in both ethnic groups (P = 0.027 and P = 0.010, respectively).
      CONCLUSION: The presence of the apo E4 isoform was associated with a higher level
      of Lp-PLA(2) index, a marker of vascular inflammation. Our results suggest that
      genetic variation at the apoE locus may impact cardiovascular disease risk
      through enhanced vascular inflammation.

PMID- 22632923
TI  - [Evaluation of the actions increasing health accessibility for deaf pregnant
      patients].
AB  - OBJECTIVES: Deafness concerns about 7% of the French population. In this context,
      the clinic of obstetrics and gynecology of Grenoble teaching hospital established
      two adaptation actions in the pregnant signing-deaf patient's management: a
      partnership with French Sign Language interpreters from the deaf patient
      reception and care unit, and sign language training for nine professionals. The
      aim of this study is to evaluate this patient management and to propose some
      potential improvements. MATERIAL AND METHODS: This descriptive study is made
      through information from both numeric and paper files of 22 deaf pregnant
      patients. RESULTS: A significant adaptation of patient management during
      scheduled consultations and hospitalisation in the clinic is observed, whereas
      adaptation rate is weak for emergency situations. CONCLUSION: The patient
      management adaptation turns out to be perfectible, through the anticipation of
      the entire pregnancy consultation schedule. In emergency situations, the creation
      of a sign language interpreter on-call duty would greatly improve the health care
      access of these patients.

PMID- 22632924
TI  - Hemochromatosis and bipolar disorder.

PMID- 22632925
TI  - A randomized controlled trial of telephone motivational interviewing to enhance
      mental health treatment engagement in Iraq and Afghanistan veterans.
AB  - OBJECTIVE: To test the efficacy of telephone-administered motivational
      interviewing (MI) to enhance treatment engagement in Iraq and Afghanistan
      veterans with mental health (MH) problems. METHOD: Between April 23, 2008, and
      February 25, 2011, 73 Iraq and Afghanistan veterans who screened positive for >=1
      MH problem(s) on telephone-administered psychometric assessment, but were not
      engaged in treatment, were randomized to either personalized referral for MH
      services and four sessions of telephone MI or standard referral and four neutral
      telephone check-in sessions (control) at baseline, 2, 4 and 8 weeks. Blinded
      assessment occurred at 8 and 16 weeks. RESULTS: In intent-to-treat analyses, 62%
      assigned to telephone MI engaged in MH treatment compared to 26% of controls
      [relative risk (RR)=2.41, 95% confidence interval (CI)=1.33-4.37, P=.004], which
      represented a large effect size (Cohen's h=0.74). Participants in the MI group
      also demonstrated significantly greater retention in MH treatment than controls
      [MI mean visits (S.D.)=1.68 (2.73) and control mean visits (S.D.)=0.38 (0.81),
      incidence rate ratio (IRR)=4.36, 95% CI=1.96-9.68, P<.001], as well as
      significant reductions in stigma and marijuana use at 8 weeks (P<.05).
      CONCLUSIONS: Telephone MI enhances MH treatment engagement in Iraq and
      Afghanistan veterans with MH problems.

PMID- 22632926
TI  - Delirium and decisional incapacity in veterans with schizophrenia and medical
      illness.
AB  - OBJECTIVE: The objective was to examine the characteristics of Veterans with
      schizophrenia admitted for nonpsychiatric hospitalizations. METHOD: We conducted
      a review of the electronic medical record and data warehouse downloads of
      Veterans with schizophrenia admitted to nonpsychiatric services of a large,
      academic Veterans Affairs hospital between 2004 and 2009 on whom psychiatry was
      consulted. RESULTS: Seventy-four veterans were admitted 89 times. Their mean age
      was 62 years. Among these veterans, the most common reasons for nonpsychiatric
      admission were infection, cardiac disease or altered mental status. Thirty-three
      percent of consultations were for patients who required intensive care.
      Consultation was requested most frequently for assessing psychotropic medication,
      decision-making capacity or altered mental status, or for assistance with
      behavioral problems. Thirty-seven percent of patients were diagnosed with
      delirium, and 42% lacked decision-making capacity, mostly secondary to delirium.
      Twenty-seven percent of patients died during the study period. CONCLUSION: In an
      aging cohort of Veterans with schizophrenia, a substantial proportion of patients
      developed delirium, lost decision-making capacity and required intensive care
      during nonpsychiatric hospital admission.

PMID- 22632927
TI  - Escitalopram-induced word finding difficulty.
AB  - Escitalopram is the most selective serotonin reuptake inhibitor used for
      treatment of major depressive disorder and generalized anxiety disorder. No
      available report indicating escitalopram may induce word finding difficulty. Here
      we are presenting a 50-year-old patient who suffered from escitalopram-induced
      word finding difficulty and the symptom resolved after replacing with bupropion.
      Carefully monitoring word finding difficulty and speech fluency during
      antidepressant treatment is important in clinical practice when using selective
      serotonin reuptake inhibitors, especially escitalopram.

PMID- 22632928
TI  - Dexmedetomidine dose dependently decreases oral tissue blood flow during
      sevoflurane and propofol anesthesia in rabbits.
AB  - PURPOSE: The aim of the present study was to investigate the effect of
      dexmedetomidine (DEX) continuous infusion on blood flow in rabbit oral tissues
      during sevoflurane or propofol anesthesia. METHODS: A total of 24 male
      tracheotomized Japanese white rabbits were anesthetized with sevoflurane or
      propofol under mechanical ventilation. An initial loading dose of 6.0 MUg/kg/hr
      DEX was administered for 10 minutes. DEX was then maintained at 0.2, 0.4, and 0.6
      MUg/kg/hr for 1 hour, respectively. The observed variables were systolic blood
      pressure, diastolic blood pressure, mean arterial pressure, heart rate, common
      carotid artery blood flow, tongue mucosal blood flow (TBF), mandibular bone
      marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue
      blood flow (UBF), lower alveolar tissue blood flow (LBF), and vascular resistance
      for each tissue (tongue mucosal vascular resistance, mandibular bone marrow
      vascular resistance, masseter muscle vascular resistance, upper alveolar tissue
      vascular resistance, and lower alveolar tissue vascular resistance). RESULTS: The
      heart rate, systolic blood pressure, mean arterial pressure, common carotid
      artery blood flow, TBF, BBF, MBF, UBF, and LBF showed dose-dependent decreases
      during DEX infusion during both sevoflurane and propofol anesthesia. The
      decreasing ratios in TBF, BBF, MBF, UBF, and LBF were greater than those in heart
      rate, systolic blood pressure, mean arterial pressure, and common carotid artery
      blood flow. The vascular resistance of the oral tissues was increased in a dose
      dependent manner during DEX infusion in both sevoflurane and propofol anesthesia.
      CONCLUSION: Our findings suggest that infusion of DEX decreases TBF, BBF, MBF,
      UBF, and LBF in a dose-dependent manner without significant changes in systemic
      hemodynamic variables during sevoflurane or propofol anesthesia.

PMID- 22632929
TI  - Primary study of the use of a shape-memory alloy distraction device in the dog
      mandible for alveolar ridge distraction: determination of osteotomy techniques
      and evaluation of osteogenesis outcome.
AB  - PURPOSE: The titanium-nickel shape-memory alloy distractor is a new kind of
      alveolar ridge distraction device that can be completely buried and self
      activated. To evaluate this new device, the present study compared the effects of
      2 osteotomy techniques and investigated the osteogenesis outcome by measuring the
      bone mineral density and biomechanical properties of newly generated bone
      tissues. MATERIALS AND METHODS: Adult mongrel canines (n = 18) were randomly
      divided into 3 groups. All the mandibular teeth were extracted. Group I received
      a complete osteotomy, whereas groups II and III received a partial osteotomy with
      preservation of the glossal cortical bones. The left mandible served as the
      experimental site for each group, and the right side served as the internal
      control. Groups I and II were sacrificed 3 months after the completion of
      distraction, whereas group III was sacrificed 6 months after the completion of
      distraction. Radiographs were taken. Dual-energy x-ray absorptiometric results
      and compressive biomechanics of the distracted and control bone masses were
      examined for groups II and III (partial osteotomy group). RESULTS: The complete
      osteotomy group exhibited a larger distraction space initially; however, the
      distracted area showed a remarkable depression on the buccal-glossal side. In
      contrast, the partial osteotomy groups exhibited a nearly normal mandibular
      morphology. The bone mineral density, compressive strength, and elastic modulus
      were decreased in the distracted side compared with the control side 3 months
      after distraction. These 3 parameters increased in the distracted side 6 months
      after distraction, which did not differ significantly from those in the control
      side. CONCLUSIONS: Partial osteotomy with preservation of the glossal cortical
      bones is more suitable for alveolar ridge augmentation using the shape-memory
      alloy distraction device. The newly generated bone exhibited adequate strength,
      which can satisfy the requirements of subsequent implantation.

PMID- 22632930
TI  - Pseudo-Brown syndrome: a potential ophthalmologic sequela after a transcaruncular
      transconjunctival approach for orbital fracture repair.
AB  - PURPOSE: To prospectively assess the incidence of orthoptic anomalies and, more
      specifically, the possible development of pseudo-Brown syndrome related to
      inferior oblique muscle (IO) myotomy after the transcaruncular-transconjunctival
      approach for orbital fracture repair and its effect on the possible development
      of annoying diplopia. PATIENTS AND METHODS: We analyzed the clinical data from 14
      patients with severe isolated medial wall or combined medial wall/floor fractures
      treated using titanium meshes placed using a transcaruncular-transconjunctival
      approach. All patients were assessed with a pre- and postoperative ophthalmologic
      examination using the following methods: prisms and alternate cover test in all 9
      gaze directions, Hess-Weiss coordimetry, Maddox rod screen testing, and Harms
      wall deviometry. The Bielschowsky head-tilt and a forced duction test were also
      performed. The patients were classified into the following 2 groups: IO paretic
      underaction group and non-IO paretic-underaction group. RESULTS: Of the 14
      patients, 7 (50%) fulfilled the criteria for IO paretic-underaction. All 7
      developed double vision limited to the extreme upgaze in adduction. Four patients
      in the non-IO paretic-underaction group had double vision limited to the extreme
      upgaze in abduction that was already present preoperatively. Diplopia did not
      interfere with the daily activities in the patients from either group.
      CONCLUSIONS: The present study has demonstrated that IO myotomy associated with
      the combined transcaruncular-transconjunctival approach can result in orthoptic
      complications. Moreover, our study has shown that the development of a pseudo
      Brown syndrome related to IO underaction was not uncommon but resulted in sequela
      restricted to a very limited portion of the binocular field of vision.

PMID- 22632931
TI  - Effects of mandibular distraction osteogenesis on three-dimensional airway
      anatomy in children with congenital micrognathia.
AB  - PURPOSE: To assess the 3-dimensional (3D) computed tomography (CT) changes in
      airway size and shape in children with congenital micrognathia treated by
      mandibular distraction osteogenesis (DO). PATIENTS AND METHODS: This was a
      retrospective study of patients with congenital micrognathia, treated by
      mandibular DO, who had pre- and postoperative 3D maxillofacial CT scans from the
      hard palate to the hyoid bone. Digital 3D-CT reconstructions were made before and
      after distraction. Demographic (age, gender, and diagnosis) and anatomic (airway
      size and shape) variables were recorded and analyzed. The pre-distraction
      measures of size and shape were compared with the post-distraction measures.
      P<=.05 was considered significant. RESULTS: During the study period (1999 to
      2010), 17 children with congenital micrognathia underwent mandibular DO. Of these
      patients, 11 (3 females) met the inclusion criteria. The mean age was 6.8 years
      (range 1.3 to 20.6). All subjects had first and second pharyngeal arch
      deformities. Nine were tracheostomy dependent before distraction. Postdistraction
      increases in the anteroposterior diameter (153%), lateral airway diameter (70%),
      airway volume (76%), minimal retroglossal (162%) and retropalatal (77%), and
      minimal cross-sectional areas (282%) were obtained. The mean airway length
      decreased after distraction by 4 mm DO also affected the airway shape: the airway
      surface area and airway compactness increased after distraction. Six subjects
      were decannulated or had their tracheostomies capped. Three subjects remained
      tracheostomy dependent after distraction. The reasons for continued tracheostomy
      included copious secretions, muscle hypotonia, hypopharnygeal stenosis, and
      mandibular hypomobility. CONCLUSIONS: DO for congenital micrognathia increases
      airway size, decreases airway length, and alters the shape as measured using 3D
      CT.

PMID- 22632932
TI  - Diagnostic imaging for submandibular duct atresia: literature review and case
      report.
AB  - PURPOSE: The basic aim of this review was to retrospectively study the role of
      imaging, particularly magnetic resonance imaging, in the diagnosis of
      submandibular duct (SMD) orifice atresia. MATERIALS AND METHODS: From a
      literature review, data were collected from previously reported cases of imaged
      SMD atresia and from the present case. RESULTS: Five images, 4 from the
      literature and 1 magnetic resonance image from our case, were obtained to
      illustrate the singular appearance of SMD orifice atresia. CONCLUSIONS: To the
      authors' knowledge, this is the first study, using a review of the literature
      concerning SMD orifice atresia, to call specific attention to the role imaging
      plays in illustrating the pathognomonic presence of the uniquely dilated and
      segmented salivary duct seen in SMD orifice atresia.

PMID- 22632933
TI  - Fragment-based discovery of hydroxy-indazole-carboxamides as novel small molecule
      inhibitors of Hsp90.
AB  - Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as
      potential molecular therapeutic agents for the treatment of cancer. Here we
      describe the identification of novel small molecular weight inhibitors of Hsp90
      using a fragment based approach. Fragments were selected by docking, tested in a
      biochemical assay and the confirmed hits were crystallized. Information gained
      from X-ray structures of these fragments and other chemotypes was used to drive
      the fragment evolution process. Optimization of these high MUM binders resulted
      in 3-benzylindazole derivatives with significantly improved affinity and anti
      proliferative effects in different human cancer cell lines.

PMID- 22632934
TI  - Click chemistry-derived bivalent quinine inhibitors of P-glycoprotein-mediated
      cellular efflux.
AB  - P-glycoprotein (P-gp) effluxes a diverse set of drug substrates out of cells in
      an ATP dependent manner, thereby limiting the effective accumulation of
      therapeutic agents. Herein we demonstrate the use of click chemistry to rapidly
      generate bivalent quinine dimers, containing an intervening triazole ring, as
      potential inhibitors of P-gp mediated efflux. Calcein-AM substrate accumulation
      assays were performed in an MCF7/DX1 cell line that overexpresses P-gp to monitor
      the inhibitory activity of the clicked quinine dimers. A small library of potent
      P-gp inhibitors with varying tether lengths is reported, with the best dimer
      demonstrating low micromolar efficacy.

PMID- 22632935
TI  - Thieno[3,2-c]pyran-4-one based novel small molecules: their synthesis, crystal
      structure analysis and in vitro evaluation as potential anticancer agents.
AB  - Novel thieno[3,2-c]pyran-4-one based small molecules were designed as potential
      anticancer agents. Expeditious synthesis of these compounds was carried out via a
      multi-step sequence consisting of few steps such as Gewald reaction, Sandmeyer
      type iodination, Sonogashira type coupling followed by iodocyclization and then
      Pd-mediated various C-C bond forming reactions. The overall strategy involved the
      construction of thiophene ring followed by the fused pyranone moiety and then
      functionalization at C-7 position of the resultant thieno[3,2-c]pyran-4-one
      framework. Some of the compounds synthesized showed selective growth inhibition
      of cancer cells in vitro among which two compounds for example, 5d and 6c showed
      IC(50) values in the range of 2.0-2.5 MUM. The crystal structure analysis of an
      active compound along with hydrogen bonding patterns and molecular arrangement
      present within the molecule is described.

PMID- 22632936
TI  - Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors.
AB  - Efforts to optimize biological activity, novelty, selectivity and oral
      bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are
      described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116
      cell line were improved. On-target activity confirmation via mechanism based G2/M
      escape assay was demonstrated. Physico-chemical and ADME properties were
      optimized to improve oral bioavailability in mouse.

PMID- 22632937
TI  - Relationship between documentation status and survival for medically underserved
      Hispanic breast cancer patients.
AB  - BACKGROUND: Undocumented immigrants have been shown to be predisposed to worse
      clinical outcomes than the general population. This study examines survival in
      socioeconomically disadvantaged Hispanic documented and undocumented breast
      cancer patients. METHODS: Analysis of a prospective breast cancer database of
      patients treated in a safety-net hospital system. Overall survival was the
      primary outcome, and advanced stage at diagnosis (regional and metastatic) was a
      secondary outcome. Survival analysis and multivariate regression modeling were
      performed. RESULTS: Seven hundred fifty-one breast cancer patients were
      identified. Undocumented patients presented at an earlier age and were likely to
      present with advanced stage. After adjusting for covariates, undocumented status
      was not associated with increased mortality. The diagnosis-to-treatment interval
      was significantly longer in undocumented patients. CONCLUSIONS: Despite
      undocumented patients presenting at a younger age, they have similar mortality
      compared with documented patients. This finding is partly explained by the local
      treatment afforded by undocumented patients, further studies are necessary to
      detail the reasons for these differences in presentation and outcome.

PMID- 22632938
TI  - Differential calcium handling in two canine models of right ventricular pressure
      overload.
AB  - BACKGROUND: The purpose of this investigation was to characterize differential
      right atrial (RA) and ventricular (RV) molecular changes in Ca(2+)-handling
      proteins consequent to RV pressure overload and hypertrophy in two common, yet
      distinct models of pulmonary hypertension: dehydromonocrotaline (DMCT) toxicity
      and pulmonary artery (PA) banding. METHODS: A total of 18 dogs underwent
      sternotomy in four groups: (1) DMCT toxicity (n = 5), (2) mild PA banding over 10
      wk to match the RV pressure rise with DMCT (n = 5); (3) progressive PA banding to
      generate severe RV overload (n = 4); and (4) sternotomy only (n = 4). RESULTS: In
      the right ventricle, with DMCT, there was no change in sarcoplasmic reticulum
      Ca(2+)-ATPase (SERCA) or phospholamban (PLB), but we saw a trend toward down
      regulation of phosphorylated PLB at serine-16 (p[Ser-16]PLB) (P = 0.07).
      Similarly, with mild PA banding, there was no change in SERCA or PLB, but p(Ser
      16)PLB was down-regulated by 74% (P < 0.001). With severe PA banding, there was
      no change in PLB, but SERCA fell by 57% and p(Ser-16)PLB fell by 67% (P < 0.001).
      In the right atrium, with DMCT, there were no significant changes. With both mild
      and severe PA banding, p(Ser-16)PLB fell (P < 0.001), but SERCA and PLB did not
      change. CONCLUSIONS: Perturbations in Ca(2+)-handling proteins depend on the
      degree of RV pressure overload and the model used to mimic the RV effects of
      pulmonary hypertension. They are similar, but blunted, in the atrium compared
      with the ventricle.

PMID- 22632939
TI  - Twenty-year analysis of surgical resident operative trauma experiences.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      implemented new work-hour rules for all U.S. residency programs beginning on July
      1, 2003. The ACGME-mandated work-hour reform may have affected operative trauma
      case volumes of general surgery residents. METHODS: Using ACGME aggregate data
      collected from general surgery residency programs from 1990 to 2010, we examined
      the effect of the 2003 work-hour reform on resident operative trauma case
      volumes. RESULTS: Overall trauma cases per year declined from 78.28 in 1990 to
      38.73 in 2010. From 1990 to 2003, laparotomy, burn, and upper-gastrointestinal
      trauma cases fell at least 50%, from 9.97 to 4.85 cases/resident by 0.46 cases/y
      (95% confidence interval [CI], 0.456-0.459), 10.05 to 3.30 cases/resident by 0.61
      cases/y (95% CI, 0.609-0.617), and 3.34 to 1.01 cases/resident by 0.189 cases/y
      (95% CI, 0.188-0.189), respectively. After 2003, laparotomy and burn cases began
      to rise by 0.23 cases/y (95% CI, 0.228-0.231) and 0.36 cases/y (95% CI, 0.358
      0.368). Vascular trauma cases continued to decline from 8.63 cases/resident by
      0.197 (95% CI, 0.196-0.198) pre-reform, but by 0.102 (95% CI, 0.099-0.105) post
      reform. Junior surgical residents were increasingly involved in trauma operative
      cases from 67% in 1990 to 79% in 2010. Cardiac, pancreatic, genitourinary, and
      neurosurgical cases did not peak more than 1.95 cases/resident pre-reform.
      CONCLUSIONS: Secular trends before the 2003 work-hour reform caused a 50%
      decrease in operative trauma experience among general surgery residents. Since
      1990, junior residents have increasingly performed operative trauma. Rare trauma
      subspecialty cases remain rare. Post work-hour reform, operative trauma volumes
      have stabilized.

PMID- 22632941
TI  - EUS-guided FNA of solid pancreas tumors.
AB  - Although endoscopic ultrasonography (EUS) is considered superior to MRI and CT in
      detecting pancreatic masses, it is the ability to target and place a needle into
      suspicious lesions that has made EUS indispensible in the evaluation of patients
      with solid pancreatic tumors. Endoscopic ultrasound-guided-fine-needle aspiration
      (EUS-FNA) is an accurate and safe technique to confirm the diagnosis of
      pancreatic cancer. EUS-FNA is now the principal technique applied to obtain the
      diagnosis of malignancy. We have designed this article to address a number of the
      key technical aspects of EUS-FNA of solid pancreatic masses.

PMID- 22632940
TI  - Estrogen deficiency attenuates neovascularization in a murine model of hindlimb
      ischemia.
AB  - BACKGROUND: The possible relation between menopause and the development of
      peripheral arterial disease, especially lower extremity disease, has not been
      fully studied. To explore this issue, we investigated whether estrogen deficiency
      affected neovascularization in a murine model of hindlimb ischemia. METHODS:
      Ischemia was surgically induced in one hindlimb of oophorectomized and control
      female BALB/c mice. Neovascularization in the ischemic hindlimbs was evaluated
      using laser Doppler blood flow analysis and capillary density analysis of the
      adductor muscle. The expression of endothelial nitric oxide synthase protein in
      the adductor muscle of the ischemic hindlimbs was assessed. RESULTS: The plasma
      17-beta estradiol levels were significantly lower in the oophorectomized mice
      than in the control mice. The oophorectomized mice also had a significantly
      reduced blood perfusion index and capillary density on day 21 after the induction
      of hindlimb ischemia and significant suppression of endothelial nitric oxide
      synthase protein expression on day 3 after ischemia induction. CONCLUSIONS:
      Estrogen deficiency attenuated neovascularization in a murine model of hindlimb
      ischemia. Impaired neovascularization in oophorectomized mice might correlate
      with a reduction in endothelial nitric oxide synthase expression caused by
      estrogen deficiency.

PMID- 22632942
TI  - Endoscopic ultrasonography-guided fine-needle aspiration of pancreatic cystic
      lesions: a practical approach to diagnosis and management.
AB  - The diagnosis and management of pancreatic cystic lesions remains a challenging
      area in gastroenterology. Differentiating benign from premalignant or
      premalignant from malignant cysts is complicated by the large overlap in
      morphologic, chemical, and clinical characteristics. Imaging alone is
      insufficient to accurately characterize these lesions. Cyst aspiration and fluid
      analysis has therefore become a major research focus through which our ability to
      characterize pancreatic cystic lesions has improved, although accuracy is often
      still lacking. Future work with molecular analysis of cyst fluid, direct
      cystoscopy, and confocal laser endomicroscopy will likely further enhance the
      diagnostic accuracy of these lesions.

PMID- 22632943
TI  - Endoscopic ultrasonography-guided diagnosis of subepithelial tumors.
AB  - Subepithelial lesions are frequently discovered during routine endoscopic
      examinations. These lesions represent a wide spectrum of heterogeneous benign to
      malignant conditions. Most of these lesions are asymptomatic. There is no
      consensus regarding how to manage these lesions. Over the last 2 decades, the
      approach to these lesions has significantly improved owing to the introduction of
      endoscopic ultrasonography, fine-needle aspiration, immunohistochemical staining
      methods, and different treatment options. This article discusses the nature of
      subepithelial lesions, focusing on the most recent developments that use
      endoscopic ultrasonography to diagnose and manage these lesions.

PMID- 22632944
TI  - Endoscopic ultrasonography/fine-needle aspiration and endobronchial
      ultrasonography/fine-needle aspiration for lung cancer staging.
AB  - This article reviews different techniques available for diagnosis and staging of
      patients with non-small cell lung cancer (NSCLC). The advantages and
      disadvantages of each staging method are highlighted. The role of the
      gastroenterologist in NSCLC staging is explored. A new algorithm is proposed for
      the staging of NSCLC that incorporates endoscopic and endobronchial
      ultrasonography for mediastinal staging in patients with intrathoracic disease.

PMID- 22632945
TI  - Endoscopic ultrasonography-guided pancreatic drainage.
AB  - Surgery for pancreatic pseudocysts (PPCs) may be associated with high rates of
      complication and mortality. Since its introduction in the late 1980s, endoscopic
      drainage of PPCs has become established as an alternative nonsurgical approach.
      The obvious limitation of this technique is its relatively blind approach. The
      ideal approach for PPC puncture combines endoscopy with real-time endosonography
      using an interventional echoendoscope. Endoscopic ultrasonographic longitudinal
      scanners can be used for guidance of transmural punctures and drainage
      procedures, as well as to access a dilated pancreatic duct if the duct cannot be
      drained by conventional methods because of complete obstruction. In this chapter,
      we will review the indications, techniques and clinical algorithm for EUS-guided
      pseudocyst drainage and pancreaticogastrostomy.

PMID- 22632946
TI  - Endoscopic ultrasound-guided celiac neurolysis.
AB  - Intractable abdominal pain commonly develops in patients with pancreatic cancer.
      Oral pharmacologic therapy is ineffective for many patients and side effects
      commonly occur. Celiac neurolysis (CN) is sometimes performed to enhance pain
      relief. Percutaneous approaches were initially described, with endoscopic
      ultrasound (EUS)-guided CN more recently introduced. There is uncertainty
      regarding the efficacy and role of CN in managing pancreatic cancer pain, but CN
      should still be considered in this difficult-to-treat cohort of patients. EUS
      guided approaches may be favored when EUS is otherwise indicated for diagnostic
      or staging purposes. When EUS is not otherwise indicated, percutaneous approaches
      are likely favored.

PMID- 22632947
TI  - Endoscopic ultrasonography-guided biliary drainage: rendezvous technique.
AB  - The success rate of deep biliary cannulation is high but still not perfect in
      endoscopic retrograde cholangiopancreatography (ERCP), even with aggressive
      techniques. With the development of linear-array echoendoscopes, the endoscopic
      ultrasonography-guided rendezvous technique (EUS-RV) has recently emerged as a
      salvage method for failed biliary cannulation. This review of current literature
      establishes that EUS-RV is a feasible and safe technique and should be considered
      as an alternative to percutaneous or surgical approaches. The availability of a
      percutaneous salvage (if EUS-RV fails) and well-trained endoscopists for both
      ERCP and EUS are mandatory in minimizing the potential complications of this
      procedure.

PMID- 22632948
TI  - Endoscopic ultrasound-guided choledochoduodenostomy for malignant lower biliary
      tract obstruction.
AB  - Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is a novel
      alternative to percutaneous transhepatic biliary drainage, when endoscopic
      retrograde cholangiopancreatography is unsuccessful in patients with malignant
      lower biliary obstruction. Some case series and a few prospective studies of EUS
      CDS have reported high technical and functional success rates but with the
      downside of high early complication rates, albeit mostly nonsevere. In addition,
      the stents placed by EUS-CDS had a longer patency than transpapillary biliary
      stents.

PMID- 22632949
TI  - Endoscopic ultrasonography-guided hepaticogastrostomy.
AB  - To date, percutaneous transhepatic biliary drainage (PTBD) has been considered as
      the usual biliary access after failed endoscopic retrograde
      cholangiopancreatography (ERCP). Since endoscopic ultrasonography (EUS)-guided
      bile duct puncture was first described in 1996, sporadic case reports of EUS
      guided biliary drainage (EUS-BD) have suggested it as an alternative to PTBD
      after failed ERCP. The potential benefits of EUS-BD include internal drainage,
      thus avoiding long-term external drainage in cases where external PTBD drainage
      catheters cannot be internalized. EUS-guided hepaticogastrostomy (EUS-HG) is one
      form of EUS-BD. This article describes the indications, techniques, and outcomes
      of published data on EUS-HG.

PMID- 22632950
TI  - Endoscopic ultrasound-guided abscess drainage.
AB  - Abdominal and pelvic abscesses have traditionally been drained by percutaneous
      techniques or surgery. While surgical drainage is associated with considerable
      morbidity and mortality, percutaneous techniques are associated with the need for
      multiple interventions, increased length of hospital stay, and an indwelling
      external catheter for prolonged periods. Endoscopic ultrasound (EUS) is a
      minimally invasive but highly effective technique that enables internal drainage
      of the abscess. Although data are limited, evidence supporting its clinical
      efficacy is increasing rapidly. This article summarizes the current status of EUS
      guided approach for drainage of gastrointestinal abscess collections.

PMID- 22632908
TI  - The benefits and harms of intravenous thrombolysis with recombinant tissue
      plasminogen activator within 6 h of acute ischaemic stroke (the third
      international stroke trial [IST-3]): a randomised controlled trial.
AB  - BACKGROUND: Thrombolysis is of net benefit in patients with acute ischaemic
      stroke, who are younger than 80 years of age and are treated within 4.5 h of
      onset. The third International Stroke Trial (IST-3) sought to determine whether a
      wider range of patients might benefit up to 6 h from stroke onset. METHODS: In
      this international, multicentre, randomised, open-treatment trial, patients were
      allocated to 0.9 mg/kg intravenous recombinant tissue plasminogen activator (rt
      PA) or to control. The primary analysis was of the proportion of patients alive
      and independent, as defined by an Oxford Handicap Score (OHS) of 0-2 at 6 months.
      The study is registered, ISRCTN25765518. FINDINGS: 3035 patients were enrolled by
      156 hospitals in 12 countries. All of these patients were included in the
      analyses (1515 in the rt-PA group vs 1520 in the control group), of whom 1617
      (53%) were older than 80 years of age. At 6 months, 554 (37%) patients in the rt
      PA group versus 534 (35%) in the control group were alive and independent (OHS 0
      2; adjusted odds ratio [OR] 1.13, 95% CI 0.95-1.35, p=0.181; a non-significant
      absolute increase of 14/1000, 95% CI -20 to 48). An ordinal analysis showed a
      significant shift in OHS scores; common OR 1.27 (95% CI 1.10-1.47, p=0.001).
      Fatal or non-fatal symptomatic intracranial haemorrhage within 7 days occurred in
      104 (7%) patients in the rt-PA group versus 16 (1%) in the control group
      (adjusted OR 6.94, 95% CI 4.07-11.8; absolute excess 58/1000, 95% CI 44-72). More
      deaths occurred within 7 days in the rt-PA group (163 [11%]) than in the control
      group (107 [7%], adjusted OR 1.60, 95% CI 1.22-2.08, p=0.001; absolute increase
      37/1000, 95% CI 17-57), but between 7 days and 6 months there were fewer deaths
      in the rt-PA group than in the control group, so that by 6 months, similar
      numbers, in total, had died (408 [27%] in the rt-PA group vs 407 [27%] in the
      control group). INTERPRETATION: For the types of patient recruited in IST-3,
      despite the early hazards, thrombolysis within 6 h improved functional outcome.
      Benefit did not seem to be diminished in elderly patients. FUNDING: UK Medical
      Research Council, Health Foundation UK, Stroke Association UK, Research Council
      of Norway, Arbetsmarknadens Partners Forsakringsbolag (AFA) Insurances Sweden,
      Swedish Heart Lung Fund, The Foundation of Marianne and Marcus Wallenberg, Polish
      Ministry of Science and Education, the Australian Heart Foundation, Australian
      National Health and Medical Research Council (NHMRC), Swiss National Research
      Foundation, Swiss Heart Foundation, Assessorato alla Sanita, Regione dell'Umbria,
      Italy, and Danube University.

PMID- 22632951
TI  - Endoscopic ultrasound-guided pancreatic cyst ablation.
AB  - Pancreatic cystic neoplasms represent a wide spectrum of invariably benign to
      precancerous and malignant tumors. Endoscopic ultrasound-guided pancreatic cyst
      ablation with ethanol and/or paclitaxel offers a nonoperative treatment for
      patients refusing or not eligible for surgery. Histopathology after resection in
      these patients has shown variable degrees of cyst epithelial ablation ranging
      from 0% to 100%. Future research investigating the safety of this procedure,
      modifications of reported ablation techniques, choice and number of the lavage
      agents used, and criteria to optimize selection of the appropriate pancreatic
      cysts for treatment is needed.

PMID- 22632952
TI  - EUS-guided vascular access and therapy.
AB  - The gastrointestinal tract provides a unique window to access vascular structures
      in the mediastinum and abdomen. The advent of interventional endoscopic
      ultrasound (EUS) has enabled access to these structures with standard fine-needle
      aspiration. EUS-guided treatment of varices has been largely reserved as rescue
      therapy for refractory bleeding but has theoretic advantages over conventional
      endoscopy-guided treatment. Data are limited and multicenter, prospective
      controlled trials are needed to show clinical effectiveness and safety in humans.
      The development of new tools designed for EUS-guided vascular therapy is needed.

PMID- 22632953
TI  - Endoscopic ultrasound-guided antitumor agents.
AB  - The development of linear-array endoscopic ultrasonography (EUS), with its real
      time guidance of needle advancement, changed EUS from a diagnostic procedure to
      an interventional procedure. EUS-guided fine-needle injection (EUS-FNI) is an
      attractive minimally invasive delivery system with potential applications in
      local (intratumoral) and combination therapy against esophageal and pancreatic
      cancers. The evidence of the feasibility of EUS-FNI of antitumor agents has been
      expanding with promising results.

PMID- 22632954
TI  - Endoscopic ultrasound-guided fiducial markers and brachytherapy.
AB  - Endoscopic ultrasound (EUS)-guided needle placement of small radiopaque particles
      paves the way for EUS-guided fiducial markers and brachytherapy. Stereotactic
      body radiation therapy relies on image-guided radiation therapy (IGRT),
      permitting escalation of radiation dose to tumors while minimizing dose to normal
      tissues. Fiducial markers are radiopaque spheres, coils, or seeds that are
      implanted in or near tumors for IGRT. Brachytherapy is a therapeutic modality for
      various cancers. Both require precise and minimally-invasive seed placement,
      which EUS provides. This article reviews recent literature regarding the safety
      and efficacy of these procedures and discusses novel concepts, including EUS
      guided celiac ganglia radiation neurolysis.

PMID- 22632955
TI  - Endoscopic ultrasound image enhancement elastography.
AB  - Endoscopic ultrasound (EUS) represents an advance in the diagnosis and staging of
      several diseases. EUS-guided fine-needle aspiration is useful, but technically
      demanding, and can be associated with complications. Elastography emerges as a
      useful tool that is based on the knowledge that some diseases, like cancer, lead
      to a modification in tissue stiffness. Elastography evaluates the elastic
      properties of tissues and compares images obtained before and after compression
      to target tissues; differentiating benign from malignant lesions. This article
      reviews theoretical aspects and the methodology of EUS elastography. Clinical
      applications, mainly in pancreatic diseases and lymph nodes, are analyzed.

PMID- 22632956
TI  - Endoscopic ultrasound: contrast enhancement.
AB  - The development of ultrasound contrast agents has allowed for the evaluation of
      vascularity in digestive organs by contrast-enhanced endoscopic ultrasonography
      (EUS). Contrast-enhanced Doppler EUS and contrast-enhanced harmonic EUS (CH-EUS)
      have improved characterization of pancreatic tumors, lymph nodes, and
      gastrointestinal submucosal tumors and compliment EUS fine-needle aspiration
      (FNA) in identifying malignant tumors. Moreover, CH-EUS can be used to identify
      the target for EUS-guided FNA by clearly depicting the outline of the lesions.

PMID- 22632957
TI  - Endoscopic ultrasonography-guided tumor ablation.
AB  - With the introduction of curvilinear endosonoscopes, endoscopic ultrasonography
      (EUS) has achieved the role of a therapeutic modality as well as diagnostic
      procedure. EUS-guided tumor ablation is one such therapeutic modality. Various
      techniques of EUS-guided tumor ablation have been described, including
      radiofrequency ablation, photodynamic therapy, laser ablation, and ethanol
      injection. Most of the currently described techniques are experimental.
      Development and continuous improvement of devices, as well as establishment of
      indications for EUS-guided tumor ablations, are mandatory.

PMID- 22632958
TI  - EUS-guided anastomosis.
AB  - Although some technical challenges in the development of dedicated devices need
      to be overcome, endoscopic ultrasonography (EUS)-guided anastomosis is promising
      as a minimally invasive technique for pancreatobiliary diseases.

PMID- 22632959
TI  - Endo-hepatology: a new paradigm.
AB  - Recent advances in hepatology have included a new and effective treatment of
      viral hepatitis, with an increased need for the assessment of liver function and
      histology. At the same time, there have been a growing number of endoscopic
      procedures that are pertinent to patients with liver disease. It would be ideal
      if the assessment and treatment of liver disease and portal hypertension could be
      performed and assimilated by the liver/gastrointestinal specialist. The authors
      like to consider this area of integration or overlap of endoscopic procedures
      within the practice of hepatology as endo-hepatology.

PMID- 22632960
TI  - Interventional endoscopic ultrasound. Foreword.

PMID- 22632961
TI  - Interventional endoscopic ultrasound.

PMID- 22632962
TI  - Tumor archaeology reveals that mutations love company.

PMID- 22632963
TI  - It takes KASH to hitch to the SUN.

PMID- 22632964
TI  - Ironing out cell death mechanisms.

PMID- 22632965
TI  - Feeling the squeeze: live-cell extrusion limits cell density in epithelia.

PMID- 22632966
TI  - Transmissible proteins: expanding the prion heresy.

PMID- 22632967
TI  - Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome
      integrity and DNA repair.
AB  - F-box proteins are the substrate binding subunits of SCF (Skp1-Cul1-F-box
      protein) ubiquitin ligase complexes. Using affinity purifications and mass
      spectrometry, we identified RRM2 (the ribonucleotide reductase family member 2)
      as an interactor of the F-box protein cyclin F. Ribonucleotide reductase (RNR)
      catalyzes the conversion of ribonucleotides to deoxyribonucleotides (dNTPs),
      which are necessary for both replicative and repair DNA synthesis. We found that,
      during G2, following CDK-mediated phosphorylation of Thr33, RRM2 is degraded via
      SCF(cyclin F) to maintain balanced dNTP pools and genome stability. After DNA
      damage, cyclin F is downregulated in an ATR-dependent manner to allow
      accumulation of RRM2. Defective elimination of cyclin F delays DNA repair and
      sensitizes cells to DNA damage, a phenotype that is reverted by expressing a
      nondegradable RRM2 mutant. In summary, we have identified a biochemical pathway
      that controls the abundance of dNTPs and ensures efficient DNA repair in response
      to genotoxic stress.

PMID- 22632968
TI  - LINC complexes form by binding of three KASH peptides to domain interfaces of
      trimeric SUN proteins.
AB  - Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the nuclear
      envelope and are composed of KASH and SUN proteins residing in the outer and
      inner nuclear membrane, respectively. LINC formation relies on direct binding of
      KASH and SUN in the perinuclear space. Thereby, molecular tethers are formed that
      can transmit forces for chromosome movements, nuclear migration, and anchorage.
      We present crystal structures of the human SUN2-KASH1/2 complex, the core of the
      LINC complex. The SUN2 domain is rigidly attached to a trimeric coiled coil that
      prepositions it to bind three KASH peptides. The peptides bind in three deep and
      expansive grooves formed between adjacent SUN domains, effectively acting as
      molecular glue. In addition, a disulfide between conserved cysteines on SUN and
      KASH covalently links both proteins. The structure provides the basis of LINC
      complex formation and suggests a model for how LINC complexes might arrange into
      higher-order clusters to enhance force-coupling.

PMID- 22632969
TI  - Direct observation of the interconversion of normal and toxic forms of alpha
      synuclein.
AB  - Here, we use single-molecule techniques to study the aggregation of alpha
      synuclein, the protein whose misfolding and deposition is associated with
      Parkinson's disease. We identify a conformational change from the initially
      formed oligomers to stable, more compact proteinase-K-resistant oligomers as the
      key step that leads ultimately to fibril formation. The oligomers formed as a
      result of the structural conversion generate much higher levels of oxidative
      stress in rat primary neurons than do the oligomers formed initially, showing
      that they are more damaging to cells. The structural conversion is remarkably
      slow, indicating a high kinetic barrier for the conversion and suggesting that
      there is a significant period of time for the cellular protective machinery to
      operate and potentially for therapeutic intervention, prior to the onset of
      cellular damage. In the absence of added soluble protein, the assembly process is
      reversed and fibrils disaggregate to form stable oligomers, hence acting as a
      source of cytotoxic species.

PMID- 22632970
TI  - Ferroptosis: an iron-dependent form of nonapoptotic cell death.
AB  - Nonapoptotic forms of cell death may facilitate the selective elimination of some
      tumor cells or be activated in specific pathological states. The oncogenic RAS
      selective lethal small molecule erastin triggers a unique iron-dependent form of
      nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon
      intracellular iron, but not other metals, and is morphologically, biochemically,
      and genetically distinct from apoptosis, necrosis, and autophagy. We identify the
      small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells
      and glutamate-induced cell death in organotypic rat brain slices, suggesting
      similarities between these two processes. Indeed, erastin, like glutamate,
      inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)),
      creating a void in the antioxidant defenses of the cell and ultimately leading to
      iron-dependent, oxidative death. Thus, activation of ferroptosis results in the
      nonapoptotic destruction of certain cancer cells, whereas inhibition of this
      process may protect organisms from neurodegeneration.

PMID- 22632971
TI  - Network crosstalk dynamically changes during neutrophil polarization.
AB  - How complex signaling networks shape highly coordinated, multistep cellular
      responses is poorly understood. Here, we made use of a network-perturbation
      approach to investigate causal influences, or "crosstalk," among signaling
      modules involved in the cytoskeletal response of neutrophils to chemoattractant.
      We quantified the intensity and polarity of cytoskeletal marker proteins over
      time to characterize stereotyped cellular responses. Analyzing the effects of
      network disruptions revealed that, not only does crosstalk evolve rapidly during
      polarization, but also that intensity and polarity responses are influenced by
      different patterns of crosstalk. Interestingly, persistent crosstalk is arranged
      in a surprisingly simple circuit: a linear cascade from front to back to
      microtubules influences intensities, and a feed-forward network in the reverse
      direction influences polarity. Our approach provided a rational strategy for
      decomposing a complex, dynamically evolving signaling system and revealed
      evolving paths of causal influence that shape the neutrophil polarization
      response.

PMID- 22632972
TI  - Planar cell polarity links axes of spatial dynamics in neural-tube closure.
AB  - Neural-tube closure is a critical step of embryogenesis, and its failure causes
      serious birth defects. Coordination of two morphogenetic processes--convergent
      extension and neural-plate apical constriction--ensures the complete closure of
      the neural tube. We now provide evidence that planar cell polarity (PCP)
      signaling directly links these two processes. In the bending neural plates, we
      find that a PCP-regulating cadherin, Celsr1, is concentrated in adherens
      junctions (AJs) oriented toward the mediolateral axes of the plates. At these
      AJs, Celsr1 cooperates with Dishevelled, DAAM1, and the PDZ-RhoGEF to upregulate
      Rho kinase, causing their actomyosin-dependent contraction in a planar-polarized
      manner. This planar-polarized contraction promotes simultaneous apical
      constriction and midline convergence of neuroepithelial cells. Together our
      findings demonstrate that PCP signals confer anisotropic contractility on the
      AJs, producing cellular forces that promote the polarized bending of the neural
      plate.

PMID- 22632973
TI  - The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin
      sensitivity, and tumorigenesis.
AB  - Akt kinase plays a central role in cell growth, metabolism, and tumorigenesis.
      The TRAF6 E3 ligase orchestrates IGF-1-mediated Akt ubiquitination and
      activation. Here, we show that Akt ubiquitination is also induced by activation
      of ErbB receptors; unexpectedly, and in contrast to IGF-1 induced activation, the
      Skp2 SCF complex, not TRAF6, is a critical E3 ligase for ErbB-receptor-mediated
      Akt ubiquitination and membrane recruitment in response to EGF. Skp2 deficiency
      impairs Akt activation, Glut1 expression, glucose uptake and glycolysis, and
      breast cancer progression in various tumor models. Moreover, Skp2 overexpression
      correlates with Akt activation and breast cancer metastasis and serves as a
      marker for poor prognosis in Her2-positive patients. Finally, Skp2 silencing
      sensitizes Her2-overexpressing tumors to Herceptin treatment. Our study suggests
      that distinct E3 ligases are utilized by diverse growth factors for Akt
      activation and that targeting glycolysis sensitizes Her2-positive tumors to
      Herceptin treatment.

PMID- 22632974
TI  - Ca(V)1 and Ca(V)2 channels engage distinct modes of Ca(2+) signaling to control
      CREB-dependent gene expression.
AB  - Activity-dependent gene expression triggered by Ca(2+) entry into neurons is
      critical for learning and memory, but whether specific sources of Ca(2+) act
      distinctly or merely supply Ca(2+) to a common pool remains uncertain. Here, we
      report that both signaling modes coexist and pertain to Ca(V)1 and Ca(V)2
      channels, respectively, coupling membrane depolarization to CREB phosphorylation
      and gene expression. Ca(V)1 channels are advantaged in their voltage-dependent
      gating and use nanodomain Ca(2+) to drive local CaMKII aggregation and trigger
      communication with the nucleus. In contrast, Ca(V)2 channels must elevate
      [Ca(2+)](i) microns away and promote CaMKII aggregation at Ca(V)1 channels.
      Consequently, Ca(V)2 channels are ~10-fold less effective in signaling to the
      nucleus than are Ca(V)1 channels for the same bulk [Ca(2+)](i) increase.
      Furthermore, Ca(V)2-mediated Ca(2+) rises are preferentially curbed by uptake
      into the endoplasmic reticulum and mitochondria. This source-biased buffering
      limits the spatial spread of Ca(2+), further attenuating Ca(V)2-mediated gene
      expression.

PMID- 22632975
TI  - A distal axonal cytoskeleton forms an intra-axonal boundary that controls axon
      initial segment assembly.
AB  - AnkyrinG (ankG) is highly enriched in neurons at axon initial segments (AISs)
      where it clusters Na(+) and K(+) channels and maintains neuronal polarity. How
      ankG becomes concentrated at the AIS is unknown. Here, we show that as neurons
      break symmetry, they assemble a distal axonal submembranous cytoskeleton,
      comprised of ankyrinB (ankB), alphaII-spectrin, and betaII-spectrin, that defines
      a boundary limiting ankG to the proximal axon. Experimentally moving this
      boundary altered the length of ankG staining in the proximal axon, whereas
      disruption of the boundary through silencing of ankB, alphaII-spectrin, or betaII
      spectrin expression blocked AIS assembly and permitted ankG to redistribute
      throughout the distal axon. In support of an essential role for the distal
      cytoskeleton in ankG clustering, we also found that alphaII and betaII-spectrin
      deficient mice had disrupted AIS. Thus, the distal axonal cytoskeleton functions
      as an intra-axonal boundary restricting ankG to the AIS.

PMID- 22632976
TI  - Contact chemoreceptors mediate male-male repulsion and male-female attraction
      during Drosophila courtship.
AB  - The elaborate courtship ritual of Drosophila males is dictated by neural
      circuitry established by the transcription factor Fruitless and triggered by sex
      specific sensory cues. Deciphering the role of different stimuli in driving
      courtship behavior has been limited by the inability to selectively target
      appropriate sensory classes. Here, we identify two ion channel genes belonging to
      the degenerin/epithelial sodium channel/pickpocket (ppk) family, ppk23 and ppk29,
      which are expressed in fruitless-positive neurons on the legs and are essential
      for courtship. Gene loss-of-function, cell-inactivation, and cell-activation
      experiments demonstrate that these genes and neurons are necessary and sufficient
      to inhibit courtship toward males and promote courtship toward females. Moreover,
      these cells respond to cuticular hydrocarbons, with different cells selectively
      responding to male or female pheromones. These studies identify a large
      population of pheromone-sensing neurons and demonstrate the essential role of
      contact chemosensation in the early courtship steps of mate selection and
      courtship initiation.

PMID- 22632977
TI  - Identification of the cortical neurons that mediate antidepressant responses.
AB  - Our understanding of current treatments for depression, and the development of
      more specific therapies, is limited by the complexity of the circuits controlling
      mood and the distributed actions of antidepressants. Although the therapeutic
      efficacy of serotonin-specific reuptake inhibitors (SSRIs) is correlated with
      increases in cortical activity, the cell types crucial for their action remain
      unknown. Here we employ bacTRAP translational profiling to show that layer 5
      corticostriatal pyramidal cells expressing p11 (S100a10) are strongly and
      specifically responsive to chronic antidepressant treatment. This response
      requires p11 and includes the specific induction of Htr4 expression. Cortex
      specific deletion of p11 abolishes behavioral responses to SSRIs, but does not
      lead to increased depression-like behaviors. Our data identify corticostriatal
      projection neurons as critical for the response to antidepressants, and suggest
      that the regulation of serotonergic tone in this single cell type plays a pivotal
      role in antidepressant therapy.

PMID- 22632978
TI  - Contingency and statistical laws in replicate microbial closed ecosystems.
AB  - Contingency, the persistent influence of past random events, pervades biology. To
      what extent, then, is each course of ecological or evolutionary dynamics unique,
      and to what extent are these dynamics subject to a common statistical structure?
      Addressing this question requires replicate measurements to search for emergent
      statistical laws. We establish a readily replicated microbial closed ecosystem
      (CES), sustaining its three species for years. We precisely measure the local
      population density of each species in many CES replicates, started from the same
      initial conditions and kept under constant light and temperature. The covariation
      among replicates of the three species densities acquires a stable structure,
      which could be decomposed into discrete eigenvectors, or "ecomodes." The largest
      ecomode dominates population density fluctuations around the replicate-average
      dynamics. These fluctuations follow simple power laws consistent with a geometric
      random walk. Thus, variability in ecological dynamics can be studied with CES
      replicates and described by simple statistical laws.

PMID- 22632979
TI  - SnapShot: directed differentiation of pluripotent stem cells.

PMID- 22632980
TI  - Perspectives toward the stereotype production method for public symbol design: a
      case study of novice designers.
AB  - This study investigated the practices and attitudes of novice designers toward
      user involvement in public symbol design at the conceptual design stage, i.e. the
      stereotype production method. Differences between male and female novice
      designers were examined. Forty-eight novice designers (24 male, 24 female) were
      asked to design public symbol referents based on suggestions made by a group of
      users in a previous study and provide feedback with regard to the design process.
      The novice designers were receptive to the adoption of user suggestions in the
      conception of the design, but tended to modify the pictorial representations
      generated by the users to varying extents. It is also significant that the male
      and female novice designers appeared to emphasize different aspects of user
      suggestions, and the female novice designers were more positive toward these
      suggestions than their male counterparts. The findings should aid the
      optimization of the stereotype production method for user-involved symbol design.

PMID- 22632981
TI  - Recent advances in formation, properties, and applications of polymersomes.
AB  - Polymersomes are self-assembled spherical vesicles based on amphiphilic block
      copolymers. This review presents a summary of the achievements in the field of
      polymersome researches to date. Polymersomes have been applied as versatile drug
      carriers. Some polymersomes, which have well-known stimuli-responsibility, can
      release drugs in a controlled manner at the target site when they are given a
      specific stimulation such as pH, temperature, light, magnetic field, hydrogen
      bond actions, electrostatic force or ultrasound. The preparation methods of
      polymersomes are similar to that of liposomes, including the thin film
      rehydration technique, solvent method, direct dissolution, double emulsion in
      microfluidic device, and electroformation. In addition, biologically active
      ligands, such as antibodies, can be readily conjugated onto the exterior brush
      surface of polymersomes to target the vesicles or to provide a therapeutic
      response. Polymersomes offer superior advantages for future clinical therapeutic
      and diagnostic imaging applications.

PMID- 22632982
TI  - Recent advance in the design of small molecular modulators of estrogen-related
      receptors.
AB  - The estrogen-related receptors (ERRs), comprising ERRalpha, ERRbeta and ERRgamma,
      are the members of the nuclear receptor superfamily, which have been functionally
      implicated in estrogen signal pathway in various patterns. However, no natural
      ligand of ERRs has been identified to data, so identification of the synthetic
      modulators (inverse agonist and agonist) of ERRs would be highly effective in the
      treatment of estrogen-related pathologies, such as diabetes, breast cancer and
      osteoporosis. This review summarizes the structures and biological functions of
      ERR subtypes, and the progress in designing the small molecular modulators of
      ERRs as well as the detailed description of available co-crystal structures of
      the LBD of ERRs in three distinct states: unligand, inverse agonist bound, and
      agonist bound.

PMID- 22632983
TI  - Association between chronic insomnia and depression in elderly adults.

PMID- 22632984
TI  - Electrophysiological characterization of Charcot-Marie-Tooth disease type 1A in
      Taiwan.
AB  - BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common type
      of hereditary neuropathy. The demyelinating pathology of CMT1A results in
      significant nerve conduction slowing such that a nerve conduction study (NCS) is
      important in the clinical assessment of CMT1A. In this study, we analyzed and
      reported the electrophysiological features of a large Taiwanese cohort with
      CMT1A. METHODS: We retrospectively analyzed the NCS data of 106 Taiwanese
      patients with CMT1A. We also compared the electrophysiological parameters of the
      CMT1A patients with those of 20 patients with early-onset Charcot-Marie-Tooth
      disease type 1B (CMT1B). RESULTS: The patients with CMT1A had a significant but
      variable degree of slowed nerve conduction. The median motor nerve conduction
      velocities (MNCVs) varied from 10.0 to 37.3 m/s in the entire CMT1A cohort but
      were more concordant in patients within a family (p<0.001). In each patient, the
      MNCVs among different nerves were concordant (p<0.001), and the MNCVs tended to
      remain steady longitudinally. Moreover, younger patients had a slower MNCV than
      older patients within the CMT1A population (p<0.001). The average median MNCV was
      significantly faster in the CMT1A patients than in the CMT1B patients (21.8+/-6.2
      m/s and 16.3+/-3.6 m/s; p<0.001). CONCLUSION: This study provides basic
      electrophysiological knowledge about CMT1A in Taiwan. The findings also suggest
      that the electrophysiological variability in the CMT1A cohort may be at least
      partially attributable to unknown genetic factors. These data emphasize the role
      of MNCV in the clinical assessment of CMT1A. A median or ulnar MNCV below 38 m/s
      can be a sensitive criterion for supporting the diagnosis of CMT1A. A median MNCV
      can sometimes help to distinguish CMT1A from CMT1B, and CMT1A should be
      considered in patients with median MNCVs near or above 24 m/s. Moreover, the MNCV
      may to some degree reflect the severity of CMT1A.

PMID- 22632985
TI  - Role of preoperative PET-CT in assessing mediastinal and hilar lymph node status
      in early stage lung cancer.
AB  - BACKGROUND: Positron emission tomography combined with computed tomography (PET
      CT) is important in the assessment and workup of lung cancer staging. However,
      inconsistencies between clinical image results obtained and pathologic findings
      of surgical specimens are still very common, particularly in patients with
      clinical early stage lung cancer. We sought to clarify the role of PET-CT in
      predicting mediastinal lymph node status preoperatively in clinical early stage
      lung cancer patients. METHODS: The cases were collected retrospectively from
      January 2008 to February 2009. All patients were good surgical candidates, and
      clinically early-stage during the pre-op evaluation, which included CT, PET scan,
      and cardiopulmonary tests. All patients underwent surgery, with complete
      pathological evaluation of mediastinal lymph node (LNs). The pathological status
      and PET Standardized uptake value (SUV)(max) of mediastinal LNs were collected to
      calculate the ROC curve, and to determine the best cut-off value of PET SUV(max).
      Other cofactors, including sex, tumor size, tumor SUV(max), histology type, and
      lobar distribution, were analyzed utilizing correlation study, Chi-square test,
      and t-test for significance. RESULTS: A total of 83 patients were enrolled into
      the study. The majority of the cases were in pathological early stage (Stage I:
      67.5%, Stage II: 12%). The cut-off point of mediastinal LN SUV(max) was 1.6
      calculated by receiver operating characteristic (ROC) curve (sensitivity: 40%,
      specificity: 88.7%, negative predictive rate: 95.1%). The hilar LN SUV(max) was
      found to have a poor correlation to the final pathologic status of hilar nodes
      with insignificant p value (0.487). Tumor SUV(max) and increased hilar LN uptake
      (SUV(max) >  2.0) were found to be significantly correlated with the pathologic
      status of mediastinal LNs. The false positive rates by PET-CT scan in N1 and N2
      nodes were 70% and 78%, respectively, primarily due to inflammatory process (as
      anthracosis the leading cause). CONCLUSION: Integrated PET-CT is a useful tool
      for predicting the negativity of mediastinal LN status pre-operatively in
      clinically early stage (Stages I and II) lung cancer but may be relatively
      inaccurate in predicting hilar LN status and largely confounded by false
      positives caused by inflammatory process.

PMID- 22632986
TI  - Children with food refusal: an assessment of parental eating attitudes and their
      styles of coping with stress.
AB  - BACKGROUND: In this study, we aimed to assess the eating attitudes and stress
      coping styles of parents whose children presented to the clinic complaining of
      food refusal. METHODS: The parents of 31 children aged >=3 years, presented to
      the clinic with the complaint of food refusal. The control group consisted of 30
      healthy children with no prior history of food refusal, and their parents. In
      both groups, birth features, body mass indexes (BMIs), eating attitudes and
      stress coping styles of the parents were assessed. The parents of both groups
      were studied, in part utilizing the eating attitudes test (EAT), and the coping
      styles of stress scale (CSSS). RESULTS: Our study found that body weights and BMI
      values of the fathers in the study group were significantly lower than fathers in
      the control group. There was no significant difference in EAT scores between the
      two groups; however, where the children's body weight and height for age
      percentile was under 25%, the parents had significantly lower EAT scores. When
      CSSS scores were assessed, the optimistic approach score of the mother and the
      self-confident score of the father were found to be significantly high in both
      groups. CONCLUSION: The parental perception and definition of eating problems
      does not necessarily indicate the presence of an eating disorder in a child. In
      fact, the eating attitudes of the fathers were related to the low percentile
      weight and height values of the children, and a child's food refusal was not
      dependent on the stress coping style used by the parent.

PMID- 22632987
TI  - The role of autologous bone graft in surgical treatment of hypertrophic nonunion
      of midshaft clavicle fractures.
AB  - BACKGROUND: This study was conducted to evaluate the results of treating
      hypertrophic nonunion of mid-shaft clavicle fracture with a limited contact
      dynamic compression plate (LC-DCP) without autologous cancellous bone graft.
      METHODS: From 1995 to 2008, 51 cases of hypertrophic nonunion of mid-shaft
      clavicle fracture were managed with open reduction and internal fixation by LC
      DCP without bone graft involvement. Of these 51 cases, 30 had nonunion after
      failure of initial surgical treatment (Group 1), and 21 had nonunion after
      failure of conservative treatment (Group 2). Preoperative and postoperative case
      management were the same for both groups, with the average follow-up period being
      20.4 months (range 18-36). Our study evaluated the radiographic results and
      functional outcomes of these cases according to the quick disability of arm,
      shoulder, and hand score. RESULTS: All 51 cases resulted in uneventful unions.
      There was no statistically significant difference between the two groups
      regarding patient demography, cause of injury, preoperative and postoperative
      functional scores, length of operation, union time, and duration of
      hospitalization (p>0.05). CONCLUSION: LC-DCP fixation is an effective method for
      treating hypertrophic nonunion of mid-shaft clavicle fracture. Local bone graft
      is sufficient to achieve necessary union, and autologous bone graft from other
      sites of the body appears unnecessary.

PMID- 22632988
TI  - Impact of hospice care on end-of-life hospitalization of elderly patients with
      lung cancer in Taiwan.
AB  - BACKGROUND: This study investigated the impact of hospice care on end-of-life
      elderly patients with lung cancer in Taiwan. METHODS: Data were collected from
      deceased inpatients with lung cancer who were at least 65 years old, using the
      National Health Insurance Research Database of 2004. RESULTS: A total of 1282
      patients were enrolled, of whom 277 (21.6%) received hospice care (hospice-care
      group) and the other 1005 (78.4%) received general acute ward care (control
      group). The patients' age, gender, and institution of hospitalization did not
      differ significantly between the two groups, and most of the patients had chosen
      medical centers and their affiliated hospices for terminal care. The hospice-care
      group had a significantly shorter hospital stay and lower costs of
      hospitalization than the control group, with patients cared for primarily by
      family physicians and radiation oncologists (all p<0.05). The hospice-care group
      had an elevated incidence of co-morbid diabetes mellitus, higher scores on the
      Charlson Comorbidity Index, fewer acute lower respiratory conditions, and fewer
      invasive procedures than the control group (all p<0.05). Natural opium alkaloids
      were the most commonly prescribed drugs in the hospice-care group, whereas
      parenteral solutions were most frequently requested in the control group.
      CONCLUSION: Hospice care has provided a humane and cost-efficient pathway for end
      of-life elderly patients with lung cancer. Parenteral nutrition/hydration should
      be limited for terminal care patients. Opioids should be promoted for the relief
      of pain and dyspnea in acute ward care. Family physicians and radiation
      oncologists play important roles in hospice care. Compared with the prevalence of
      hospice care in the United Kingdom and other developed countries, hospice care in
      Taiwan is in the position to be expanded.

PMID- 22632989
TI  - To add or not to add? An empirical study on droperidol and intravenous patient
      controlled analgesia.
AB  - BACKGROUND: Droperidol is commonly added to intravenous patient-controlled
      analgesia (IVPCA) regimens as an antiemetic agent. Although some studies have
      demonstrated its safety and efficacy, it is not clear whether adding droperidol
      to IVPCA infusate without an extra loading dose can effectively reduce the
      incidence and severity of postoperative nausea and vomiting (PONV) in real-life
      clinical settings. METHODS: Patients receiving IVPCA in this retrospective survey
      were classified into two groups based on their IVPCA regimens. The droperidol
      group used morphine 1mg/mL with droperidol 50 MUg/mL, and the non-droperidol
      group was given morphine 1 mg/mL alone. The incidence and severity of PONV were
      compared between the two groups during the 3-day course of IVPCA treatment using
      logistic regression and ordinal logistic regression. Propensity score methodology
      was applied to adjust for potential confounders. RESULTS: Among the 186 patients
      enrolled, 94 patients received IVPCA with droperidol, and 92 patients received a
      pure morphine solution. There was no significant difference in patient attributes
      between the two groups. On the 1st postoperative day, there was no significant
      difference in incidence or severity of PONV between the two groups. From the 2nd
      day onward, the patients in the droperidol group had significantly fewer and less
      severe episodes of PONV (relative risk 0.34 and 0.31, respectively). The overall
      effects of droperidol on PONV and its severity during the whole IVPCA course were
      also statistically significant, whether or not adjustment for propensity score
      was made. However, although a statistically significant decrease in nausea was
      observed in the droperidol group after the 1st day, no significant difference in
      the incidence of vomiting between the two groups was noted during the study.
      CONCLUSION: A loading dose should be considered on the 1st postoperative day. Our
      study suggests just how beneficial droperidol can be to IVPCA users in practical
      clinical settings, showing that droperidol can reduce with some significance the
      amount and severity of nausea suffered by patients postoperatively, even if the
      frequency of patient vomiting remains unchanged.

PMID- 22632990
TI  - Drug abuse-related accidents leading to emergency department visits at two
      medical centers.
AB  - BACKGROUND: Drug abuse is becoming more prevalent in Taiwan, as evidenced by
      increasing reports of drug trafficking and drug abuse-related criminal activity,
      and the wide use of more contemporary illicit drugs. Consequently, drug abuse
      related accidents are also expected to occur with greater frequency. However, no
      study has yet specifically evaluated the prevalence, pattern, and outcomes of
      drug abuse-related accidents among patients visiting emergency departments (EDs)
      in Taiwan. METHODS: We conducted an ambidirectional study with patients who
      visited the EDs of Taipei Veterans General Hospital (TVGH) and China Medical
      University Hospital (CMUH) due to drug abuse-related accidents from January 2007
      through September 2009. Information on the patients' baseline characteristics and
      clinical outcomes was collected and analyzed. RESULTS: During the study period, a
      total of 166 patients visited the EDs of one of the two study hospitals due to
      drug abuse-related accidents. This yielded a prevalence of drug abuse of 0.1%
      among all patients visiting the ED due to accident and/or trauma. Fifty-six out
      of the 166 patients visited the ED at TVGH, most patients being between 21 and 40
      years old. Opioids (41.1%) were the drugs most commonly abused by the patients,
      followed by benzodiazepines (32.1%). More than two-thirds of the patients (n=38,
      67.9%) required hospitalization, and three patients died (5.4%). In contrast, 110
      patients with drug abuse-related accidents visited the ED at CMUH during the
      study period. Most of these subjects had abused benzodiazepines (69.1%), were
      between 21 and 40 years old, and were female. Fewer than one-fifth of the
      patients (n=19, 17.3%) required hospitalization, with no deaths reported. There
      were significant between-hospital differences in terms of patient gender, drugs
      of choice, injury mechanisms, method and time of the ED visit, triage levels, and
      need for hospitalization. CONCLUSION: Although the prevalence of drug abuse
      related accidents was low, and only three patient deaths were reported in this
      study, many patients presented to the EDs with severe effects and later required
      hospitalization. Better and timely management of such patients will help to
      minimize the adverse health impacts associated with drug abuse. Governmental
      agencies and all healthcare professionals should also work together to fight
      against the surging trend of drug abuse in Taiwan.

PMID- 22632991
TI  - Renal mucinous tubular and spindle cell carcinoma with an aorto-caval mass
      mimicking metastatic lymphadenopathy.
AB  - A 54-year-old female had a 9-cm left renal mass with a 12-cm aorto-caval mass
      lesion mimicking an enlarged lymph node. Retroperitoneal dissection and left
      radical nephrectomy were performed, and pathology revealed a left renal mucinous
      tubular and spindle cell carcinoma combined with a retroperitoneal
      ganglioneuroma. The patient has had no local recurrence or distant metastasis
      after 3 years' follow-up. A misdiagnosis of metastatic renal cell carcinoma may
      be upheld by the primary imaging studies. Even in the targeted therapy era,
      cytoreductive nephrectomy is still an important step in the diagnosis and
      treatment of suspicious metastatic renal cell carcinomas.

PMID- 22632992
TI  - Acute life-threatening arrhythmias caused by severe hyperkalemia after induction
      of anesthesia in an infant with methylmalonic acidemia.
AB  - Methylmalonic acidemia (MMA) is a very rare genetic disease of metabolism that
      progressively leads to neurological and renal sequelae. This report describes an
      unusual case of a patient with MMA who developed severe hyperkalemia and severe
      dysrhythmia during anesthesia. A 13-month-old male infant with MMA underwent
      urgent insertion of a port-a-cath under general anesthesia. A life-threatening
      arrhythmia suddenly occurred, with severe hyperkalemia (up to 7.4 mmol/L),
      immediately following induction of anesthesia. Emergent resuscitation was
      successfully carried out, with a complete neurological recovery after 7 days
      after surgery. Although MMA is a rare complication, the possibility of severe
      hyperkalemia should be considered in the differential diagnosis of patients with
      MMA presenting with wide QRS complex tachycardia. The management and
      intraoperative complications of this disorder are reported here, and the
      available literature is reviewed.

PMID- 22632993
TI  - [Acute fulminating emphysematous cholecystitis after cardiac surgery].

PMID- 22632995
TI  - [Cerebral air embolism complicating talc pleurodesis: case report].
AB  - Cerebral air embolism is a severe complication which can occur during many
      invasive medical procedures. Its prognosis depends on early diagnosis and
      hyperbaric oxygen therapy. We report a case of cerebral air embolism which
      occurred during a talc pleurodesis within a chest tube, in chest postoperative
      period. After early and appropriate treatment, we observed a significant
      functional recovery.

PMID- 22632997
TI  - The effect of Se salts on DNA structure.
AB  - There is considerable interest in the role of selenium in cancer prevention.
      Various organic and inorganic Se compounds are considered to be antioxidants. In
      the present study, the binding modes, the binding constants and the stability of
      Se-DNA complexes have been determined by Fourier transform infrared (FTIR) and UV
      Visible spectroscopic methods. Spectroscopic evidence showed that Na(2)SeO(4) and
      Na(2)SeO(3) bind to the minor and major grooves of DNA and the backbone phosphate
      (PO(2)) with overall binding constants of K(Na(2)SeO(4)-DNA)=5.20*10(4) M(-1) and
      K(Na(2)SeO(3)-DNA)=1.87*10(3) M(-1). DNA aggregations occurred at high selenium
      concentrations. No biopolymer conformational changes were observed upon
      Na(2)SeO(3) and Na(2)SeO(4) interactions, while DNA remained in the B-family
      structure.

PMID- 22632996
TI  - Combined treatment of heavy calcified femoro-popliteal lesions using directional
      atherectomy and a paclitaxel coated balloon: One-year single centre clinical
      results.
AB  - BACKGROUND: The use of directional atherectomy (DA) for the treatment of
      calcified femoro-popliteal lesions seems to improve the acute procedural success,
      however without reducing the long term restenosis rate. Drug coated balloons
      (DCB) reduced restenosis rate in non heavy calcified lesions. Aim of this study
      was to demonstrate safety and efficacy of a combined endovascular approach using
      DA and DCB for the treatment of heavy calcified lesions of the femoro-popliteal
      tract. METHODS: From January 2010 to November 2010, 240 patients underwent PTA of
      the femoro-popliteal tract in our institution. Within this cohort a total of 30
      patients had life limiting claudication (LLC) (n=18) and 12 a critical limb
      ischemia (CLI) with baseline Rutherford class 4.2+/-1.2 underwent PTA of heavy
      calcified lesions with intravascular ultrasound guided DA and DCB. All procedures
      have been performed using a distal protection device. Stent implantation was
      allowed only in case of flow limiting dissections or suboptimal result (residual
      stenosis>50%) by visual estimation. After the intervention patients were followed
      up to 12 months. RESULTS: Procedural and clinical success, was achieved in all
      cases. Bail-out stenting was necessary in only two (6.5%). At twelve month follow
      up median Rutherford class was 2.2+/-1.2, ABI was 0.8+/-0.1 and Limb salvage rate
      was 100%. Two minor, foot finger or forefoot amputations, were performed to reach
      complete wound healing and/or preserve deambulation. Duplex control was performed
      in all the cases (n=30). In three cases duplex scan showed a significant target
      lesion restenosis requiring a reintervention (TLR=10%) leading a total one-year
      secondary patency rate of 100%. All the three restenosed patients were insulin
      dependent diabetics and none of them were stented during the procedure.
      CONCLUSION: The data suggest that combined use of DA and DCB may represent a
      potential alternative strategy for the treatment of femoro-popliteal severely
      calcified lesions. These very promising data and the considered hypothesis have
      to be confirmed in a multicentre randomised trial.

PMID- 22632998
TI  - Towards international agreement on criteria for Guillain-Barre syndrome.

PMID- 22632999
TI  - Are high-frequency (600 Hz) oscillations in human somatosensory evoked potentials
      due to phase-resetting phenomena?
AB  - OBJECTIVE: Median nerve somatosensory evoked potentials (SEP) contain a brief
      oscillatory wavelet burst at about 600 Hz (sigma-burst) superimposed on the
      initial cortical component (N20). While invasive single-cell recordings suggested
      that this burst is generated by increased neuronal spiking activity in area 3b,
      recent non-invasive scalp recordings could not reveal concomitant single-trial
      added-activity, suggesting that the SEP burst might instead be generated by phase
      reset of ongoing high-frequency EEG. Here, a statistical model and exemplary data
      are presented reconciling these seemingly contradictory results. METHODS: A
      statistical model defined the conditions required to detect added-activity in a
      set of single-trial SEP. Its predictions were tested by analyzing human single
      trial scalp SEP recorded with custom-made low-noise amplifiers. RESULTS: The
      noise level in previous studies did not allow to detect single-trial added
      activity in the period concomitant with the trial-averaged sigma-burst. In
      contrast, optimized low-noise recordings do reveal added-activity in a set of
      single-trials. CONCLUSIONS: The experimental noise level is the decisive factor
      determining the detectability of added-activity in single-trials. A low-noise
      experiment provided direct evidence that the SEP sigma-burst is at least partly
      generated by added-activity matching earlier invasive single-cell recordings.
      SIGNIFICANCE: Quantitative criteria are provided for the feasibility of single
      trial detectability of band-limited added-activity.

PMID- 22633000
TI  - An anti-phosphoinositide-specific monoclonal antibody that neutralizes HIV-1
      infection of human monocyte-derived macrophages.
AB  - HIV-1 entry into cells requires the interaction of both HIV-1 envelope proteins
      and membrane lipids. We investigated the mechanism of neutralization of HIV-1
      infection of primary monocyte-derived macrophages (MDM) by a murine monoclonal
      antibody (mAb) WR321. WR321 specifically binds phosphatidylinositol-4-phosphate
      and phosphatidylinositol-4,5-bisphosphate. These phosphoinositides are present
      not only on the inner surface of the plasma membranes of cells but also on the
      surface of virions. HIV-1 acquires these lipids during the budding process. Pre
      incubation of WR321 with the virus but not with MDM neutralized HIV-1 infection
      of MDM. Our results demonstrate that WR321 was internalized only when it was
      bound to HIV-1. WR321 did not prevent the entry of HIV-1 into MDM. However, once
      WR321 was internalized along with HIV-1 the mAb acted intracellulary to prevent
      the release of virions from MDM and also triggered the release of beta
      chemokines.

PMID- 22633001
TI  - First case of ovarian Sertoli-Leydig cell tumor after an allogeneic hematopoietic
      stem cell transplantation for Hodgkin's disease.

PMID- 22632994
TI  - Constructing and random sequencing analysis of normalized cDNA library of testis
      tissue from oriental river prawn (Macrobrachium nipponense).
AB  - The oriental river prawn, Macrobrachium nipponense, is an important aquaculture
      species in China. Sexual precocity is a serious problem because of genetic
      retrogression, which has negative effects on product quality and dramatically
      affects price. Culture of all-male populations of this species would be
      economically advantageous, as the males grow faster and reach a much larger size
      than females. Developing such a culture scheme will require discovery of sex- or
      reproduction-related genes that affect sexual maturity and sex determination. In
      this study, a high-quality normalized testis cDNA library was constructed to
      identify novel transcripts. Of the 5280 successful sequencing reaction yields,
      5202 expressed tagged sequences (ESTs) with an average length of 954 bp.
      Ultimately, 3677 unique sequences, including 891 contigs and 2786 singletons,
      were identified based on cluster and assembly analyses. Sixteen hundred (43.5%)
      genes were novel based on the NCBI protein database, thus these unidentified
      genes may improve basic molecular knowledge about M. nipponense. Of the novel
      unigenes, 34.4% (715/2077) were homologous to insects, such as Tribolium
      castaneum, Drosophila spp. and Apis mellifera. Fifty-two genes were identified as
      sex- or reproduction-related based on Gene Ontology classification and sequence
      comparison with data from other publications. These genes can be classified into
      groups based on different functions, including 10 sex-determination related
      genes, 8 male-reproductive genes, 5 cathepsin-related genes, 20 ubiquitin-related
      genes, 5 ferritin-related genes, and 4 LRR genes. The results of this study
      provide new sequence information about M. nipponense, which will be the basis for
      further genetic studies of this species and other decapods crustaceans.

PMID- 22633002
TI  - Selective toxicity towards myelodysplastic hematopoietic progenitors - another
      rationale for iron chelation in MDS.

PMID- 22633003
TI  - PROSE treatment of corneal ectasia.
AB  - PURPOSE: Prosthetic replacement of the ocular surface ecosystem (PROSE) uses
      custom designed and fabricated prosthetic devices in a treatment that restores
      vision, supports healing, reduces symptoms and improves quality of life in
      patients with complex corneal disease. We report the success rate for PROSE
      treatment of corneal ectasia. METHODS: Records of 59 patients with corneal
      ectasia seen in consultation over 6 months were reviewed. Candidacy for
      treatment, topographic indices, change in visual acuity, achievement of
      satisfactory fit, device wear status and change in visual function at 6 months
      were recorded. RESULTS: Sixteen eyes were non-candidates because conventional
      correction was adequate. Trial devices were inserted but not dispensed for 13
      eyes. No eyes were excluded for severity of ectasia. In the remaining 89 eyes,
      satisfactory fit was achieved and a device was dispensed. Twenty-one eyes (15
      patients) had undergone penetrating keratoplasty. Device wear at 6 months was
      documented in 78/89 eyes (88%). NEI VFQ-25 score improved 27.6 points (p<0.001)
      on a 100 point scale in patients wearing a device at 6 months. CONCLUSION: All
      candidate eyes with corneal ectasia could be fitted with a PROSE device. PROSE
      treatment has a high success rate when measured by ability to achieve
      satisfactory fit, impact on visual acuity and 6 month data on both rate of
      continued wear and impact on visual function. PROSE treatment is an alternative
      to penetrating keratoplasty for patients with corneal ectasia who are contact
      lens intolerant.

PMID- 22633005
TI  - Synthetic aperture imaging in breast ultrasound: a preliminary clinical study.
AB  - RATIONALE AND OBJECTIVES: To compare the image quality between conventional and
      synthetic aperture (SA) imaging in breast ultrasound (US). MATERIALS AND METHODS:
      Twenty-four patients with 31 breast lesions were included in our study. The US
      data were processed with SA algorithm. For quantitative analysis, contrast-to
      noise ratio (CNR) and signal-to-noise ratio (SNR) were calculated. For
      qualitative analysis, conventional and SA images were reviewed by three
      radiologists and diagnostic preference (conspicuity, margin sharpness, and
      contrast) was assessed. The radiologists also determined whether artifacts were
      present. Parameters were analyzed using a paired t-test, Wilcoxon signed-rank
      test, and chi-square test. RESULTS: The mean CNRs were higher in SA images
      compared with conventional images (mean, 2.56 versus 2.28, P = .004). The mean
      SNRs were higher in SA images compared with conventional images (31.62 versus
      25.26, P < .0001). SA images were considered as being "better" or "much better"
      in 16-23 (51.6-74.2%) lesions of total 31 lesions for conspicuity, in 17-24
      (45.2%-77.4%) for margin sharpness, and in 13-23 (41.9%-74.2%) for contrast.
      Significant preferences in SA images were demonstrated (conspicuity, P < .05 for
      all radiologists; margin sharpness and contrast in two radiologists). Refraction
      and speckle artifacts were less frequently observed in SA images (refraction, P <
      .05 for all radiologists; speckle, P < .05 for two radiologists), whereas
      reflection artifacts were more frequent in SA images (P < .05 in two
      radiologists). CONCLUSION: SA imaging provides better image quality than
      conventional imaging in patients with focal breast lesions in breast US.

PMID- 22633004
TI  - Sounds exaggerate visual shape.
AB  - While perceiving speech, people see mouth shapes that are systematically
      associated with sounds. In particular, a vertically stretched mouth produces a
      /woo/ sound, whereas a horizontally stretched mouth produces a /wee/ sound. We
      demonstrate that hearing these speech sounds alters how we see aspect ratio, a
      basic visual feature that contributes to perception of 3D space, objects and
      faces. Hearing a /woo/ sound increases the apparent vertical elongation of a
      shape, whereas hearing a /wee/ sound increases the apparent horizontal
      elongation. We further demonstrate that these sounds influence aspect ratio
      coding. Viewing and adapting to a tall (or flat) shape makes a subsequently
      presented symmetric shape appear flat (or tall). These aspect ratio aftereffects
      are enhanced when associated speech sounds are presented during the adaptation
      period, suggesting that the sounds influence visual population coding of aspect
      ratio. Taken together, these results extend previous demonstrations that visual
      information constrains auditory perception by showing the converse - speech
      sounds influence visual perception of a basic geometric feature.

PMID- 22633006
TI  - Kinematic and kinetic changes in obese gait in bariatric surgery-induced weight
      loss.
AB  - This study examines the effects of a radical bariatric surgery-induced weight
      loss on the gait of obese subjects. We performed a three-dimensional motion
      analysis of lower limbs, and collected force platform data in the gait laboratory
      to calculate knee and hip joint moments. Subjects (n=13) performed walking trials
      in the laboratory before and 8.8 months (SD 4.2) after the surgical procedure at
      two gait speeds (1.2m/s and 1.5m/s). The average weight loss was 26.7kg (SD
      9.2kg), corresponding to 21.5% (SD 6.8%) of the initial weight. We observed a
      decrease in step width at both gait speeds, but no changes in relative double
      support or swing time or stride length. A significant decrease was noted in the
      absolute values of peak knee abductor, peak knee flexor and peak hip extensor
      moments. However, the moment values normalized by the body weight and height
      remained unchanged in most cases. Thus, we conclude that weight loss reduces hip
      and knee joint moments in proportion to the amount of weight lost.

PMID- 22633007
TI  - A shoe sole-based apparatus and method for randomly perturbing the stance phase
      of gait: test-retest reliability in young adults.
AB  - Walking on an irregular surface is associated with an elevated risk for a fall at
      any age. Yet, relatively little is known about how a human responds to an
      unexpected underfoot perturbation during gait. This is partly due to the
      difficulty of generating an intermittent but repeatable, unexpected, underfoot
      perturbation whose size and location are precisely known. So we developed a shoe
      sole-embedded apparatus for randomly perturbing the stance phase of gait. Medial
      and lateral flaps were concealed in the soles of pairs of sandals, along with
      their actuators. Either flap could be deployed within 400ms in the parasagittal
      plane under a swing foot; this altered the resulting sagittal and frontal plane
      orientations of the foot during the next stance phase, whereafter the flap was
      retracted following toe-off for the rest of that gait trial. We tested six
      healthy young subjects by randomly presenting a single medial or lateral
      perturbation in 12 of 30 gait trials. Traditional step kinematic measures were
      used to evaluate the test-retest reliability of the response to the stimulus at
      two different walking speeds in 60 randomized trials conducted 1 week apart. The
      method was effective in systematically inducing an alteration in gait,
      reproducible across visits, as evidenced by acceptable intraclass correlation
      coefficients for step width, time and length. We conclude that the apparatus and
      method has potential for measuring the ability of humans to reject one or more
      unexpected underfoot perturbations during gait.

PMID- 22633008
TI  - Biochemical and pharmacological evaluation of 4-hydroxychromen-2-ones bearing
      polar C-3 substituents as anticoagulants.
AB  - The objective of this study was to investigate in vitro and in vivo anticoagulant
      activity of sixteen 4-hydroxycoumarin derivatives bearing polar C-3 scaffolds.
      The activity was evaluated by measuring prothrombin time. Enhanced anticoagulant
      activity in vitro was observed for all tested compounds. Upon successive
      administration of 0.5 mg/kg of body weight to adult Wistar rats, over a period of
      five days, four derivatives (2b, 4c, 5c and 9c) presented anticoagulant activity
      in vivo. The most active compound was 2b, with PT = 30.0 s. Low or non-toxic
      effects in vivo were determined based on the catalytic activity of liver enzymes
      and the concentration of bilirubin, iron and proteins. Metabolic pathways of the
      most active compounds in vivo were determined after GC/MS analysis of collected
      rat urine samples. The excretion occurs by glucuronidation of 7-hydroxy forms of
      tested derivatives. In vivo results were described using PLS-based CoMFA and
      CoMSIA 3D-QSAR studies, which showed CoMFA-SE (q(2) = 0.738) and CoMSIA-SEA (q(2)
      = 0.763) to be the statistically most relevant models. Furthermore, molecular
      docking and DFT mechanistic studies performed on the rat VKORC1 homology model
      revealed interactions between the 4-OH coumarin group in the form of phenolic
      anion and the Cys135 catalytic site in the transition state.

PMID- 22633009
TI  - Synthesis of berbamine acetyl glycosides and evaluation of antitumor activity.
AB  - A series of berbamine glycosides was designed, synthesized and evaluated as a new
      class of antitumor agents. An efficient glycosylation route was developed for
      berbamide derivatives. The newly synthesized glycosides were evaluated for their
      cytotoxic activity in vitro against a human leukemia cell line K562, a human lung
      adenocarcinoma cell line A549 and mouse lymphocytic leukemia cells L1210. In
      contrast to berbamine most of its glycosides manifested potent cytotoxic
      activities. The acetyl glycosyl berbamine 5a, 5d caused distinct improvement
      against K562, A549 and L1210. It is suggested that the acetyl D-glucose residue
      has affinity to these cancer cells.

PMID- 22633010
TI  - Association between the Rorschach Ego Impairment Index and the Level of
      Personality Organization interview assessment in depressive and anxiety disorder
      patients.
AB  - The level of personality functioning, relevant for treatment planning, can be
      evaluated by the Rorschach Comprehensive System (CS) Ego Impairment Index-2 (EII
      2) and by interview assessment of the severity of personality pathology. However,
      few studies on the association between these assessment methods have been
      reported. This study examines the strength of association between the EII-2 and
      its subcomponents with the interview-based Level of Personality Organization
      (LPO) assessment scale, and investigates their mutual associations with
      psychiatric symptoms, diagnoses, and history. Altogether, 315 mood or anxiety
      disorder outpatients without severe personality pathology were assessed with the
      LPO and tested with the CS, on which the EII-2 and its subcomponents (FQ-, WSum6,
      Critical contents, M-, PHR, GHR, and R) were calculated. Significant, but weak
      association between the EII-2 and the LPO was found. The WSum6, a measure of
      thought disorder, was the only EII-2 subcomponent significantly associated with
      the LPO. Both measures were consistently associated with psychiatric symptoms,
      diagnoses and history. The findings partially support the EII-2 and the LPO as
      consistently associated, relatively independent measures of the severity of
      personality pathology. More research on the incremental benefits of the measures
      is needed in clinical populations, covering non-severe and complex
      psychopathology.

PMID- 22633011
TI  - Factor structure analysis of the SCL-90-R in a community-based sample of African
      American women.
AB  - The empirical literature pertaining to anxiety and related disorders in African
      Americans continues to be sparse, raising significant doubt upon the valid
      assessment of anxiety and related disorders in African American samples. The
      identification of culturally valid instruments that accurately identify the
      symptomatology associated with anxiety and related constructs as well as
      differentiating individuals who meet criteria for anxiety and related disorders
      would undoubtedly enhance our understanding of anxiety and related constructs in
      diverse populations while assisting researchers in identifying ingredients for
      culturally sensitive therapies (CSTs). The current study represents a major
      stride in this area through examination of the factor structure of the Symptom
      Checklist 90-Revised (SCL-90-R) in a community-based sample of African American
      women. Ninety-one African American women completed the SCL-90-R as part of a
      larger investigation of anxiety and related disorders in African American parent
      child dyads. Results suggest that psychological distress, as measured by the SCL
      90-R, adequately fits the current data. Implications and suggestions for future
      work in this area are discussed.

PMID- 22633013
TI  - Gene expression of peripheral blood lymphocytes may discriminate patients with
      schizophrenia from controls.
AB  - To identify a classifier in schizophrenia, blood gene expression profiling was
      applied to patients with schizophrenia under different treatments and to
      controls. Expression of six genes discriminated patients with sensitivity of
      89.3% and specificity of 90%, supporting the use of peripheral blood as
      biological material for diagnosis in schizophrenia.

PMID- 22633014
TI  - Indications for positron emission tomography and bone gammagraphy in staging lung
      cancer.

PMID- 22633012
TI  - Platelet protein kinase C and brain-derived neurotrophic factor levels in
      borderline personality disorder patients.
AB  - Borderline personality disorder (BPD) is a prevalent and difficult to treat
      psychiatric condition characterized by abrupt mood swings, intense anger and
      depression, unstable interpersonal relationships, impulsive self-destructive
      behavior and a suicide rate of approximately 10%. Possible underlying molecular
      dysregulations in BPD have not been well explored. Protein kinase C (PKC) and
      brain-derived neurotrophic factor (BDNF) have both been implicated in affective
      disorders, but their role in BPD has not been examined. Platelets were isolated
      from blood obtained from 24 medication-free BPD patients and 18 healthy control
      subjects. PKC-alpha, phosphorylated-PKC-alpha (p-PKCalpha), PKC-betaII, and BDNF
      were measured in platelet homogenates by immunoblotting. In the males, platelet
      BDNF and PKC-alpha levels were lower in patients than controls. p-PKC-alpha and
      PKC-betaII were lower at trend levels. In the entire sample, platelet p-PKCalpha
      and PKC-alpha activity were lower, at a trend level, in patients compared to
      controls. This is the first report to our knowledge of PKC and BDNF activity in
      BPD and calls for replication. These findings are consistent with altered PKC and
      BDNF activity in a range of neuropsychiatric conditions including bipolar
      disorder, depression and suicide.

PMID- 22633015
TI  - Validity of the Microsoft Kinect for assessment of postural control.
AB  - Clinically feasible methods of assessing postural control such as timed standing
      balance and functional reach tests provide important information, however, they
      cannot accurately quantify specific postural control mechanisms. The Microsoft
      KinectTM system provides real-time anatomical landmark position data in three
      dimensions (3D), and given that it is inexpensive, portable and simple to setup
      it may bridge this gap. This study assessed the concurrent validity of the
      Microsoft KinectTM against a benchmark reference, a multiple-camera 3D motion
      analysis system, in 20 healthy subjects during three postural control tests: (i)
      forward reach, (ii) lateral reach, and (iii) single-leg eyes-closed standing
      balance. For the reach tests, the outcome measures consisted of distance reached
      and trunk flexion angle in the sagittal (forward reach) and coronal (lateral
      reach) planes. For the standing balance test the range and deviation of movement
      in the anatomical landmark positions for the sternum, pelvis, knee and ankle and
      the lateral and anterior trunk flexion angle were assessed. The Microsoft
      KinectTM and 3D motion analysis systems had comparable inter-trial reliability
      (ICC difference=0.06+/-0.05; range, 0.00-0.16) and excellent concurrent validity,
      with Pearson's r-values >0.90 for the majority of measurements (r=0.96+/-0.04;
      range, 0.84-0.99). However, ordinary least products analyses demonstrated
      proportional biases for some outcome measures associated with the pelvis and
      sternum. These findings suggest that the Microsoft KinectTM can validly assess
      kinematic strategies of postural control. Given the potential benefits it could
      therefore become a useful tool for assessing postural control in the clinical
      setting.

PMID- 22633016
TI  - A digit alignment device for kinematic analysis of the thumb and index finger.
AB  - Kinematic analysis of the digits using optical motion capture systems relies on
      defining accurate coordinate systems for the individual segments. Limitations of
      previous digit kinematic protocols include marker placement errors, marker
      occlusion and superimposition, and skin movement artifact. The purpose of this
      study was to develop a protocol utilizing a digit alignment device (DAD) and nail
      marker clusters to overcome these limitations. Ten subjects underwent 10 static
      calibration trials for validation. The orientation of the thumb distal phalange
      relative to the index finger distal phalange was described using Euler angles of
      pitch(x), yaw(y'), and roll(z''). The digit calibration protocol demonstrated
      high accuracy (0.5 degrees , 1.9 degrees  and 2.2 degrees  for x, y', z'') and
      precision (1.4 degrees , 2.3 degrees  and 3.1 degrees  for x, y', z''). The
      developed protocol provided convenient identification of transformations that
      determine anatomically relevant coordinate systems for the distal phalanges of
      the digits. The potential of utilizing this protocol as a standardized tool for
      digit kinematics was demonstrated using a dynamic task of precision pinching.

PMID- 22633017
TI  - Utilization of a lower extremity ambulatory feedback system to reduce gait
      asymmetry in transtibial amputation gait.
AB  - The goal of our research is to augment gait rehabilitation for persons with gait
      asymmetry through a real-time feedback system that can be used independently by
      patients in the community. Our wireless, wearable, real-time gait asymmetry
      detection system called the lower extremity ambulatory feedback system (LEAFS) is
      a low-cost, in-shoe gait detection device that provides real-time auditory
      feedback based on the stance time symmetry ratio between the right and left
      limbs. This study evaluated the performance of the LEAFS in three study subjects
      with gait asymmetry secondary to unilateral transtibial amputation. Study
      subjects used the LEAFS for six 30-min training sessions under the supervision of
      a physical therapist. Two subjects demonstrated improved gait symmetry, with one
      subject reducing trunk sway by 85.5%, and the other subject reducing trunk sway
      by 16.0% and increasing symmetry ratio toward unity by 26.5%, as measured by a
      clinical motion analysis lab. The third subject did not demonstrate any objective
      improvements in gait symmetry or trunk sway. While testing with a larger number
      of subjects is necessary, this initial study using LEAFS with persons with
      transtibial amputations suggests that it can assist in improving gait symmetry in
      this population.

PMID- 22633018
TI  - In vitro and in vivo anthelmintic activity of Euphorbia helioscopia L.
AB  - The anthelmintic potentials of the aqueous and methanol extracts of Euphorbia
      helioscopia were investigated. In folklore medicine, E. helioscopia
      (Euphorbiaceae) is used in the treatment of various gastrointestinal ailments and
      diseases. A worm motility inhibition (WMI) assay and egg hatch assay (EHA) were
      used for in vitro assessment, and a faecal egg count reduction (FECR) assay was
      used for an in vivo study. The in vitro study revealed anthelmintic effects of
      crude methanolic extracts of E. helioscopia on live Haemonchus contortus worms as
      evident from their paralysis and/or death at 8h after exposure, different
      concentrations (12.5 mg ml(-1), 25 mg ml(-1) and 50 mg ml(-1)) of aqueous and
      methanolic extracts were used against H. contortus which exhibited dose-dependent
      anthelmintic effects on H. contortus. Aqueous and methanolic extracts of aerial
      parts (stem, leaves and flowers) of E. helioscopia were found to have very low
      percent inhibitory egg hatching as compared to levamisole. It is concluded that
      the entire plant of E. helioscopia possesses significant anthelmintic activity
      and could be a potential alternative for treating cases of helminth infections in
      ruminants.

PMID- 22633019
TI  - Mental health in the USA: hopes and fears.

PMID- 22633020
TI  - Lost in transition: health of transgender people in Asia Pacific.

PMID- 22633021
TI  - Tobacco industry versus tobacco control.

PMID- 22633022
TI  - The US Global Health Initiative: where does it stand?

PMID- 22633023
TI  - Tinnitus: the end of therapeutic nihilism.

PMID- 22633024
TI  - Patient safety: an educational competency.

PMID- 22633026
TI  - Concerns about the Millennium Villages project report.

PMID- 22633027
TI  - Misleading report on clinical trials in India.

PMID- 22633029
TI  - Pregnancy should not rule out 18FDG PET/CT for women with cancer.

PMID- 22633030
TI  - Lymphadenectomy for pregnant women with stage I cervical cancer.

PMID- 22633033
TI  - Specialised treatment based on cognitive behaviour therapy versus usual care for
      tinnitus: a randomised controlled trial.
AB  - BACKGROUND: Up to 21% of adults will develop tinnitus, which is one of the most
      distressing and debilitating audiological problems. The absence of medical cures
      and standardised practice can lead to costly and prolonged treatment. We aimed to
      assess effectiveness of a stepped-care approach, based on cognitive behaviour
      therapy, compared with usual care in patients with varying tinnitus severity.
      METHODS: In this randomised controlled trial, undertaken at the Adelante
      Department of Audiology and Communication (Hoensbroek, Netherlands), we enrolled
      previously untreated Dutch speakers (aged >18 years) who had a primary complaint
      of tinnitus but no health issues precluding participation. An independent
      research assistant randomly allocated patients by use of a computer-generated
      allocation sequence in a 1:1 ratio, stratified by tinnitus severity and hearing
      ability, in block sizes of four to receive specialised care of cognitive
      behaviour therapy with sound-focused tinnitus retraining therapy or usual care.
      Patients and assessors were masked to treatment assignment. Primary outcomes were
      health-related quality of life (assessed by the health utilities index score),
      tinnitus severity (tinnitus questionnaire score), and tinnitus impairment
      (tinnitus handicap inventory score), which were assessed before treatment and at
      3 months, 8 months, and 12 months after randomisation. We used multilevel mixed
      regression analyses to assess outcomes in the intention-to-treat population. This
      study is registered with ClinicalTrials.gov, number NCT00733044. FINDINGS:
      Between September, 2007 and January, 2011, we enrolled and treated 492 (66%) of
      741 screened patients. Compared with 247 patients assigned to usual care, 245
      patients assigned to specialised care improved in health-related quality of life
      during a period of 12 months (between-group difference 0.059, 95% CI 0.025 to
      0.094; effect size of Cohen's d=0.24; p=0.0009), and had decreased tinnitus
      severity (-8.062, -10.829 to -5.295; d=0.43; p<0.0001) and tinnitus impairment (
      7.506, -10.661 to -4.352; d=0.45; p<0.0001). Treatment seemed effective
      irrespective of initial tinnitus severity, and we noted no adverse events in this
      trial. INTERPRETATION: Specialised treatment of tinnitus based on cognitive
      behaviour therapy could be suitable for widespread implementation for patients
      with tinnitus of varying severity. FUNDING: Netherlands Organisation for Health
      Research and Development (ZonMW).

PMID- 22633034
TI  - Congenital rubella syndrome: a continuing conundrum.

PMID- 22633035
TI  - Opportunities and challenges of online data collection for suicide prevention.

PMID- 22633036
TI  - Guinea pigs in human form: clinical trials in unethical settings.

PMID- 22633037
TI  - [Cancer, fertility preservation and gonadotropins].
AB  - The recent emergence of oncofertility raises the question of ovarian stimulation
      and its risks when performed for oocyte or/and embryo cryopreservation in a
      fertility preservation program. The relation between ovarian stimulation and
      cancer has been marked by the possible direct or indirect tumorigenic role for
      pituitary gonadotrophins in the tumorogenesis. Although the growth of many
      gonadal and extragonadal tumors is stimulated by gonadal sex hormones, whose
      production is regulated by gonadotrophins, there is still a lack of data to
      consider FSH and LH as tumor promoters. The purpose of this brief review is to
      present on one hand, the questions raised by the administration of exogenous
      gonadotrophins in cancer patients and on the other, to evaluate both experimental
      and clinical data about the possible relation between gonadotrophins and
      tumorogenesis.

PMID- 22633038
TI  - [Feasibility study about the single-port in gynecologic oncology surgery].
AB  - OBJECTIVES: To describe our single-port experience in gynecologic oncology
      surgery, and emphasize the feasibility to use the single-port in this surgery.
      PATIENTS AND METHODS: It is a retrospective, feasibility study, monocentric. All
      patients who were operated by the single-port, between 1st January 2010 to 1st
      November 2011, were included. RESULTS: We note that 107 patients were included.
      We made different interventions: uni- and bilateral salpingo-ovariectomy,
      hysterectomy, pelvic and para-aortic lymph node sampling or lymphadenectomy in
      gynecologic malignancies. The median age of the population and the body mass
      index were respectively 52 and 22.6 kg/m(2). In total, six interventions will be
      converted. The median hospital stay of patients, all procedures combined, was 2
      days. We find low rate of postoperative complications. CONCLUSION: Gynecological
      cancer surgery appears feasible for single-port. However, we need other studies
      to confirm a benefit of using the single-port compared to conventional
      laparoscopy.

PMID- 22633039
TI  - Flammability of topical preparations and surgical dressings in cutaneous and
      laser surgery: a controlled simulation study.
AB  - BACKGROUND: Surgical fires are a rare, but serious complication of dermatologic
      procedures involving electrosurgical and laser devices. Given the lack of data
      regarding basic fire safety principles, many dermatologists remain unaware of
      this potential risk. OBJECTIVE: We evaluated the flammability of topical
      preparations and surgical drapes commonly encountered in the immediate operative
      field during cutaneous and laser surgery. METHODS: Surgical dressings, drapes,
      and pork belly skin were examined for fire risk upon exposure to isopropyl
      alcohol, chlorhexidine gluconate, and aluminum chloride under dry, saturated, and
      damp conditions. Both electrosurgery and a carbon-dioxide laser were used as
      ignition sources. RESULTS: At least some char was observed in 86 of 126 simulated
      conditions (68%). Flames occurred in 2 test conditions: dry underpad drapes and
      cotton balls exposed to the carbon-dioxide laser. In general, drapes and
      dressings dampened or saturated with isopropyl alcohol failed to ignite with
      electrofulguration or electrodessication, although sparks and moderate char
      developed on pork belly skin and the underpad drape. Materials dampened or
      saturated with chlorhexidine gluconate, which contains isopropyl alcohol,
      generated less smoke and char compared with materials exposed to aluminum
      chloride, which does not contain alcohol. LIMITATIONS: Future studies may assess
      the flammability of materials in the setting of oxygen supplementation.
      CONCLUSION: In common cutaneous surgical environments, electrosurgery or ablative
      laser may lead to char and rarely to fire. Char may be seen in up to two thirds
      of simulated conditions, and in a minute proportion of conditions, fire is
      observed.

PMID- 22633040
TI  - Punch grafting of chronic ulcers in patients with laminin-332-deficient, non
      Herlitz junctional epidermolysis bullosa.
AB  - BACKGROUND: Epidermolysis bullosa (EB) is a genetic, heterogeneous, trauma
      induced blistering disease. Patients with laminin-332-deficient non-Herlitz
      junctional EB (JEB-nH) can have impaired wound healing witnessed by persistent,
      small, deep ulcers on the hands and feet that adversely affect the quality of
      life. OBJECTIVE: We sought to present the results of punch grafting in patients
      with laminin-332-deficient JEB-nH, and to discuss its therapeutic value. METHODS:
      Retrospective analysis of the Dutch EB Registry revealed 4 patients with laminin
      332-deficient JEB-nH who were treated with punch grafting. Punch grafting was
      performed according to protocol, and the patients were followed up. RESULTS: In
      the past 10 years we have treated 23 ulcers in 4 patients with JEB-nH using punch
      grafting without any complications or adverse effects. The ulcers had on average
      persisted 6 years before treatment. Healing rate after punch grafting was 70% (n
      = 16), with a mean healing time of 2 months. Thirty percent (n = 7) of the
      treated ulcers did not completely heal, but did show improvement. The recurrence
      rate after 3 months was 13% (n = 2), and was a result of renewed blistering.
      LIMITATIONS: Limitations of the study are the retrospective design, small number
      of patients, absence of a control group, and follow-up and ulcer measurement that
      were not standardized. CONCLUSIONS: Punch grafting can be used as a first-line
      treatment in small persistent ulcers in patients with JEB-nH. The method is easy,
      is inexpensive, has little risk of complications, and results in significant
      healing rates and improvement in quality of life.

PMID- 22633041
TI  - Management of brain AVM procedural hemorrhagic complication by the "security"
      catheter technique.
AB  - Since the introduction of Onyx as a liquid embolic agent for the treatment of
      brain arteriovenous malformation (AVM), higher endovascular cure rates have been
      achieved. This may be partially attributed to its non-adhesive property, which
      allows longer intranidal progression of the embolic agent before solidification.
      However, Onyx reflux around the microcatheter can form a highly viscous plug,
      thereby constraining the microcatheter during its retrieval. Also, during the
      maneuver, arterial stretching can lead to vascular rupture and result in acute
      bleeding, a potentially fatal complication that demands immediate treatment. This
      report describes a new treatment strategy for the rapid management of such a
      complication. The technique consists of the placement of a second microcatheter
      about 2 cm proximal to the AVM nidus in the same artery containing the intranidal
      microcatheter. After conclusion of embolization, if rupture occurs during
      intranidal microcatheter retrieval, the second microcatheter that is already in
      place can promptly be used to control the bleeding.

PMID- 22633042
TI  - Multimodal imaging approach to cerebral gas embolism lesions.
AB  - Cerebral gas embolism may be revealed by the sudden onset of unconsciousness
      sometimes after surgery or after diagnostic and therapeutic procedures. The
      clinical diagnosis may be difficult if the context is not relevant. Imaging can
      therefore play a crucial role in revealing the presence of intracranial gas
      bubbles on CT or MRI scans. This report is of a case of fatal cerebral gas
      embolism revealed by CT and MRI performed for deep and unexplained coma.
      Etiological diagnosis revealed the presence of a lung tumor invading the
      mediastinum, thus possibly allowing the migration of gas from the lung to the
      arterial cerebral circulation. A second MRI performed 8 days after the initial
      event with diffusion tensor imaging (DTI) and proton magnetic resonance
      spectroscopic imaging ((1)H-MRSI) allowed better comprehension of the
      pathophysiological mechanisms of cerebral injury secondary to gas embolism by
      showing two kinds of cerebral lesions: white-matter vasogenic edema and cytotoxic
      gray-matter edema.

PMID- 22633043
TI  - Accuracy of head ultrasound for the detection of intracranial hemorrhage in
      preterm neonates: comparison with brain MRI and susceptibility-weighted imaging.
AB  - OBJECTIVES: To evaluate the sensitivity and specificity of head ultrasound (HUS)
      in the detection of intracranial hemorrhage in premature neonates compared with
      brain MRI using susceptibility-weighted imaging (SWI). MATERIAL AND METHODS:
      Ultrasound (US) and MRI scans of the brain using SWI in premature neonates were
      retrospectively evaluated for grade I-III germinal matrix hemorrhage (GMH),
      periventricular hemorrhagic infarction (PVHI), intra-axial hemorrhage other than
      PVHI, extra-axial hemorrhage in each cerebral hemisphere and cerebellar
      hemorrhage in each cerebellar hemisphere. The impact of these hemorrhagic
      findings on short-term clinical management was also reviewed. RESULTS: Twelve
      neonates (mean age: 9.8 days; range: 3-23 days) with a mean gestational age of
      32.8 weeks (range: 29.6-35.4 weeks) were included in the study. HUS had high
      sensitivity (100%) and specificity (93.3%) in detecting grade III GMH using SWI
      as a reference, but poor sensitivity (0%) in the detection of intraventricular
      hemorrhage with normal-sized ventricles (grade II GMH). US was not sensitive in
      detecting either small cerebellar or extra-axial hemorrhage. CONCLUSION: HUS was
      highly sensitive and specific in the evaluation of grade III GMH, whereas SWI was
      superior to HUS in detecting small intra-axial or extra-axial hemorrhage, and had
      no impact on short-term management. Given the low cost, lack of radiation and
      advantages of bedside evaluation, HUS should continue to be the first line of
      imaging for brain injury in the evaluation of premature neonates with suspected
      intracranial hemorrhage. However, the usefulness of SWI for predicting long-term
      neurological outcomes has yet to be determined.

PMID- 22633044
TI  - Carotid artery stenting in patients with symptomatic carotid stenosis: a single
      center series.
AB  - OBJECTIVES: Carotid angioplasty with stenting (CAS) in patients with carotid
      stenosis (CS) has become more restricted in France especially since the
      disclosure of such studies as EVA-3S and Stent-supported percutaneous angioplasty
      of the carotid artery versus endarterectomy (SPACE). This report is of a series
      of CS cases contraindicated for endarterectomy that underwent CAS at a French
      center of interventional neuroradiology. PATIENTS AND METHODS: Fifty-five
      patients with symptomatic CS more than 60% consecutively submitted to CAS between
      September 2008 and February 2011. The primary endpoint was either death or stroke
      within 30 days of the procedure; a secondary goal was to identify any possible
      factors that might have influenced the success and outcome of the intervention.
      RESULTS: The overall periprocedural stroke/death rate at 30 days was 5.4% (three
      out of 55 patients), with three non-disabling strokes and no deaths. Twenty-seven
      patients (49.1%) were treated with a cerebral protection device (CPD). Stent
      placement was achieved in all cases. Open- and closed-cell stents were implanted
      in 40 (72.7%) and 15 procedures (27.3%), respectively. Neither the use of a CPD,
      the carotid stent cell design nor any anatomical or technical factors were
      associated with a lower risk of stroke or death within 30 days of CAS.
      CONCLUSION: CAS in symptomatic patients with CS contraindicated for
      endarterectomy in this selected French series proved feasible and safe, with
      acceptable levels of morbidity. Use of a CPD, type of stent (open- or closed
      cell), and anatomical and technical factors had no influence on the success of
      the procedure or the outcome within 30 days of the operation.

PMID- 22633045
TI  - Arterial spin labeling (ASL) magnetic resonance imaging in acute confusional
      migraine of childhood.

PMID- 22633046
TI  - Vertebral body osteolysis following the use of bone morphogenetic protein in
      spinal surgery: a mimicker of infection.
AB  - This report describes the imaging findings in three patients who developed lumbar
      spine osteolysis after posterior spinal fusion using rhBMP-2. These cases
      demonstrate the variable course of osteolysis, as well as the importance of
      recognizing its radiological appearances to prevent confusion with infection
      following spinal fusion.

PMID- 22633047
TI  - Evaluation of luminal and vessel wall abnormalities in subacute and other stages
      of intracranial vertebrobasilar artery dissections using the volume isotropic
      turbo-spin-echo acquisition (VISTA) sequence: a preliminary study.
AB  - OBJECTIVE: To evaluate the utility of 3D variable refocusing flip-angle volume
      isotropic turbo-spin-echo acquisition (VISTA) imaging, using a 1.5-T MRI unit,
      which can minimize flow artifacts, due to its sequence-endogenous flow-void
      capability, in the diagnosis of intracranial vertebrobasilar artery dissection
      (VAD). MATERIAL AND METHODS: The presence of intimal flaps, intramural hematomas,
      vessel dilatations and abnormal vessel enhancements were evaluated on T1-weighted
      VISTA images from 18 VAD patients with 20 dissected arteries (15 subacute and
      five at other stages). Additional gadolinium-enhanced T1VISTA images were
      available for 13 patients. The frequency of flow artifacts on T1VISTA imaging in
      70 non-dissected arteries in VAD patients and 12 control subjects was also
      evaluated. Furthermore, in 13 and eight patients, contrast-enhanced three
      dimensional (CE3D) imaging with spoiled gradient-recalled (SPGR) acquisition in
      steady state and electrocardiographically gated black-blood (BB) T1-weighted
      imaging (T1WI) were evaluated to compare visualization of false lumens. RESULTS:
      Intimal flaps, intramural hematomas and dilatations were identified on T1VISTA
      images in 65% (13/20), 55% (11/20) and 90% (18/20) of VADs, respectively.
      Abnormal vessel enhancement was recognized in 100% (15/15) of VADs on contrast
      enhanced T1VISTA images. Only four normal arteries showed small, thin, linear
      artifacts. Compared with CE3D-SPGR imaging, T1VISTA imaging depicted false lumens
      more conspicuously in seven VADs (P=0.02). T1VISTA also revealed intimal flaps
      and hematomas as did BB T1WI. CONCLUSION: T1VISTA imaging may be useful for
      diagnosing VAD at subacute stages, as it can reveal vessel wall and lumen
      abnormalities with a minimum of flow artifacts.

PMID- 22633048
TI  - Decompressive craniectomy and cerebral blood flow regulation in head injured
      patients: a case studied by perfusion CT.
AB  - Previous studies have reported increased cerebral blood flow (CBF) velocity after
      decompressive craniectomy in traumatic brain injury (TBI) patients. A 27-year-old
      man presented with clinical and tomographic signs of cerebral herniation
      secondary to TBI. Prior to decompressive craniectomy, hemodynamic study by
      perfusion computed tomography (CT) indicated diffuse cerebral hyperperfusion.
      Following surgical decompression, the patient recovered neurologically and
      perfusion CT disclosed a decrease in the intensity of cerebral perfusion. The
      patient's blood pressure levels were similar at both pre- and postoperative
      perfusion CT examinations. This finding provides indirect evidence that
      decompressive craniectomy may improve mechanisms of CBF regulation in TBI,
      providing pathophysiological insights in the cerebral hemodynamics of TBI
      patients. This is the first report analyzing the hemodynamic changes through
      perfusion CT (PCT) in a patient with decompressive craniotomy due to TBI.

PMID- 22633049
TI  - Autoinducer 2 of Fusobacterium nucleatum as a target molecule to inhibit biofilm
      formation of periodontopathogens.
AB  - Periodontitis is initiated by bacteria in subgingival biofilms, which are
      composed mostly of Gram-negative anaerobes. Autoinducer 2 (AI-2) is a universal
      quorum sensing (QS) molecule that mediates intergeneric signalling in
      multispecies bacterial communities and may induce biofilm formation. As
      Fusobacterium nucleatum is the major coaggregation bridge organism that links
      early colonising commensals and late pathogenic colonisers in dental biofilms via
      the accretion of periodontopathogens, we hypothesised that AI-2 of F. nucleatum
      contributes to this interspecies interaction, and interruption of this signalling
      could result in the inhibition of biofilm formation of periodontopathogens. To
      test this hypothesis, we evaluated the effect of partially purified F. nucleatum
      AI-2 on monospecies biofilm as well as mutualistic interactions between F.
      nucleatum and the so-called 'red complex' (Porphyromonas gingivalis, Treponema
      denticola, and Tannerella forsythia). Then we tested the effect of two QS
      inhibitors (QSIs), (5Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone (furanone
      compound) and d-ribose, on AI-2-induced biofilm formation and coaggregation. F.
      nucleatum AI-2 remarkably induced biofilm growth of single and dual species and
      coaggregation between F. nucleatum and each species of the 'red complex', all of
      which were inhibited by the QSIs. F. nucleatum AI-2 induced the expression of the
      representative adhesion molecules of the periodontopathogens, which were
      inhibited by the QSIs. Our results demonstrate that F. nucleatum AI-2 plays an
      important role in inter- and intraspecies interactions between
      periodontopathogens via enhanced expression of adhesion molecules and may be a
      target for the inhibition of pathogenic dental biofilm formation.

PMID- 22633050
TI  - Aberrant C nerve fibre function of the healthy scalp.
AB  - BACKGROUND: The scalp is commonly associated with itch and burning sensations.
      Previous studies have shown the scalp is highly innervated compared with other
      body areas. However, limited data are available on sensory testing associated
      with C nerve fibres of the healthy scalp. OBJECTIVE: To examine the function of C
      nerve fibre-mediated sensations such as warmth, heat pain, itch and neurogenic
      inflammation in two areas of the scalp (crown and occiput) in comparison to
      forearm skin. METHODS: Twenty-two healthy subjects (11 women, 11 men) underwent
      quantitative computerized thermosensory testing to assess warmth and heat pain
      thresholds. Itch was induced using histamine iontophoresis and application of
      cowhage spicules, and the intensity of each itch was assessed. Skin blood flow
      was measured at baseline and after each itch induction to assess degree of
      neurogenic inflammation. RESULTS: A majority (64%) of the crown warmth threshold
      measurements exceeded 50 degrees C while all 22 forearm warmth thresholds
      measurements were significantly lower than 50 degrees C. Both scalp sites had
      significantly higher warmth and heat pain thresholds compared with the forearm
      (P<0.001). Itch ratings of histamine and cowhage on both scalp sites were
      significantly lower than on the forearm (P<=0.001). Histamine and cowhage induced
      an increase in skin blood flow from baseline on the forearm compared with the
      scalp (P< 0.001). CONCLUSIONS: This study demonstrates a significant
      insensitivity of C nerve fibres of the scalp to warmth, heat pain, itch and
      neurogenic inflammation. These results suggest that the scalp has an aberrant
      response of C nerve fibres.

PMID- 22633051
TI  - [Highlighting differences in the management of neurogenic bladder existing
      between urologists and physiatrists: A survey conducted among 383 specialists].
AB  - OBJECTIVES: To investigate and evaluate the quality of care and follow-up
      provided to neurogenic patients by urologists and physiatrists in France.
      METHODS: A survey was conducted by the French-speaking group of neuro-urology
      (GENULF) among French urologists and physiatrists in 2009. Three thousand one
      hundred and eighty questionnaires were sent to the members of four scientific
      societies. Questions focused on aetiology, consultation, clinical follow-up and
      symptom management. RESULTS: Two hundred and seventy-four urologists and 109
      physiatrists completed the questionnaire, 76% and 84% respectively had experience
      in neuro-urology. Only a few specialists performed multidisciplinary
      consultations. Systematic follow-up frequency varied between 6 to 12 months.
      Eighty-three percent of physiatrists and 56% of urologists performed a urodynamic
      follow-up, mostly yearly. Physiatrists used invasive imaging techniques more
      often than urologists. They also treated asymptomatic bacteriuria in catheterised
      patients more often than urologists. Self-catheterisation was a standard
      treatment to address urinary retention. Both specialists prescribed botulinum
      toxin type A injections. DISCUSSION: National and international guidelines
      related to follow-up and treatments were followed by both specialists. Urologists
      and physiatrists treated asymptomatic bacteriuria more often than necessary.
      Urodynamics testing was not carried out as often as recommended by guidelines.
      Urologists offered a more frequent follow-up than physiatrists. Physiatrists
      performed more often and better urodynamic follow-up compared to urologists.
      CONCLUSION: Our survey revealed a good observance of national and international
      guidelines by French specialists for the management of neurogenic bladder
      patients. Nevertheless, the management of these patients could be harmonised and
      possibly improved by putting an accent on specialists' education, by using
      assessment forms regarding their practices and by increasing the amount of
      multidisciplinary consultations.

PMID- 22633052
TI  - Preferred content and usefulness of a photodiary as described by ICU-patients--a
      mixed method analysis.
AB  - Many ICU-patients have memory-gaps which may affect their recovery. A tool in the
      recovery can be an ICU-diary to explain and clarify thoughts and events from the
      ICU-period. There are different standards for the content in the ICU-diary. The
      aim of this study was to identify the preferred content and usefulness of an ICU
      diary as described by ICU-patients. METHOD: A descriptive, exploratory cohort
      design with a mixed method approach. The patients answered a questionnaire
      (n=115) and participated in an interview (n=15) six months after the ICU-stay.
      Data analysis was carried out in three stages; the questionnaire was analysed by
      descriptive statistics and categorised by content (four open-ended questions) and
      the interviews were analysed by manifest content analysis. RESULTS: The patients
      were explained that detailed information about daily activities and medical facts
      had to be included to understand and give a sense of coherence of what had
      happened. The content in the ICU-diary had to be chronological in order to follow
      the process in which photos were an important part. The patients re-read the ICU
      diary during the recovery which helped them to fill in the memory gaps and used
      it as a tool for communication. CONCLUSION: To construct a coherent story, it was
      essential that the ICU-diary was complete and were amplified by photos, all
      appearing in a chronological order. The results of this study could form a basis
      for further developments of standards and guidelines for ICU-diaries.

PMID- 22633053
TI  - The rostral parvicellular reticular formation neurons mediate lingual nerve input
      to the rostral ventrolateral medulla.
AB  - In rats that had been anesthetized by urethane-chloralose, we investigated
      whether neurons in the rostral part of the parvicellular reticular formation
      (rRFp) mediate lingual nerve input to the rostral ventrolateral medulla (RVLM),
      which is involved in somato-visceral sensory integration and in controlling the
      cardiovascular system. We determined the effect of the lingual nerve stimulation
      on activity of the rRFp neurons that were activated antidromically by stimulation
      of the RVLM. Stimulation of the lingual trigeminal afferent gave rise to
      excitatory effects (10/26, 39%), inhibitory effects (6/26, 22%) and no effect
      (10/26, 39%) on the RVLM-projecting rRFp neurons. About two-thirds of RVLM
      projecting rRFp neurons exhibited spontaneous activity; the remaining one-third
      did not. A half (13/26) of RVLM-projecting rRFp neurons exhibited a pulse-related
      activity, suggesting that they receive a variety of peripheral and CNS inputs
      involved in cardiovascular function. We conclude that the lingual trigeminal
      input exerts excitatory and/or inhibitory effects on a majority (61%) of the RVLM
      projecting rRFp neurons, and their neuronal activity may be involved in the
      cardiovascular responses accompanied by the defense reaction.

PMID- 22633054
TI  - Relationships between human adenoviruses and faecal indicator organisms in
      European recreational waters.
AB  - Human adenoviruses (HAdV) may be implicated in some disease outbreaks associated
      with recreational water exposures, typically in swimming pools. Modern molecular
      methods can be used to detect HAdV in environmental water samples. During the EU
      FP6 Project VIROBATHE a database of over 290 HAdV analyses with corresponding
      faecal indicator organism (FIO) determinations was gathered and used to explore
      statistical associations between HAdV and FIO results. The FIOs measured were
      Escherichia coli, intestinal enterococci and somatic coliphage. Statistically
      significant trends of increasing proportions of HAdV-positive results in
      categories of increasing FIO concentration were found in freshwater but not
      seawater samples. The analysis of these trends in freshwater samples was refined,
      the trends remaining statistically significant when using categories of 0.5
      log(10) intervals of FIO concentration. Logistic regression models were then
      developed to predict the probability of a HAdV-positive outcome from FIO
      concentration. Potential applications of these models to predict the probability
      of HAdV-positive outcomes from routine FIO determinations used to describe
      recreational water quality exposures and to classify recreational water quality
      are discussed.

PMID- 22633055
TI  - Childhood trauma exposure in Iraq and Afghanistan war era veterans: implications
      for posttraumatic stress disorder symptoms and adult functional social support.
AB  - OBJECTIVE: This study examined the relationship among childhood trauma,
      posttraumatic stress disorder (PTSD) symptoms, and adult social support in a
      large sample of veterans who served in the military after 09/11/2001, with a
      specific focus on the potential role of the PTSD avoidance and numbing cluster as
      intervening in the association between childhood abuse and adult functional
      social support. METHOD: Participants were 1,301 veterans and active duty soldiers
      who have served in the military since 09/11/2001; a subsample of these
      participants (n=482) completed an inventory of current functional social support.
      Analyses included linear regression and nonparametric bootstrapping procedures.
      RESULTS: After controlling for combat exposure, exposure to childhood trauma was
      associated with PTSD symptoms in adulthood. Further, PTSD symptoms, and
      particularly PTSD avoidance/numbing cluster symptoms, intervened in the
      relationship between childhood trauma and adult functional social support.
      CONCLUSIONS: Findings support the association of childhood trauma (both abuse
      related and other, non-abuse related trauma) with PTSD symptoms in military
      personnel and veterans, even after accounting for combat exposure. Additionally,
      the avoidance and numbing symptom cluster of childhood trauma-based PTSD may be
      particularly salient in compromising one's subsequent ability to garner
      functional social support in adulthood.

PMID- 22633056
TI  - Parenting stress mediates between maternal maltreatment history and maternal
      sensitivity in a community sample.
AB  - OBJECTIVE: Maternal maltreatment history and current parenting stress are
      associated with parenting difficulties. However, researchers have not
      investigated the mechanism by which these variables are interlinked. We
      hypothesized that parenting stress mediates the relation between history of
      maltreatment and parenting behavior. METHODS: We assessed a community sample of
      291 mothers as they interacted with their 16-month old infants in the home.
      Maternal history of maltreatment and parenting stress were assessed via self
      report inventory; maternal sensitivity toward the infant was assessed with 2h of
      direct behavioral observation. RESULTS: Mothers who reported more maltreatment in
      childhood were less sensitive with their infants; mothers who reported more
      current parenting stress were also less sensitive. Parenting stress mediated
      between maternal maltreatment history and current parental behavior. CONCLUSIONS:
      Findings are consistent with an interpretation of parenting stress as a pathway
      through which maternal history of maltreatment may be linked to decreased
      maternal sensitivity.

PMID- 22633057
TI  - Structural changes in the narcoleptic brain and their possible relevance for
      clinical severity.

PMID- 22633058
TI  - Hemoproteins in dissimilatory sulfate- and sulfur-reducing prokaryotes.
AB  - Dissimilatory sulfate and sulfur reduction evolved billions of years ago and
      while the bacteria and archaea that use this unique metabolism employ a variety
      of electron donors, H(2) is most commonly used as the energy source. These
      prokaryotes use multiheme c-type proteins to shuttle electrons from electron
      donors, and electron transport complexes presumed to contain b-type hemoproteins
      contribute to proton charging of the membrane. Numerous sulfate and sulfur
      reducers use an alternate pathway for heme synthesis and, frequently, uniquely
      specific axial ligands are used to secure c-type heme to the protein. This review
      presents some of the types and functional activities of hemoproteins involved in
      these two dissimilatory reduction pathways.

PMID- 22633060
TI  - Anammox--growth physiology, cell biology, and metabolism.
AB  - Anaerobic ammonium-oxidizing (anammox) bacteria are the last major addition to
      the nitrogen-cycle (N-cycle). Because of the presumed inert nature of ammonium
      under anoxic conditions, the organisms were deemed to be nonexistent until about
      15 years ago. They, however, appear to be present in virtually any anoxic place
      where fixed nitrogen (ammonium, nitrate, nitrite) is found. In various mar'ine
      ecosystems, anammox bacteria are a major or even the only sink for fixed
      nitrogen. According to current estimates, about 50% of all nitrogen gas released
      into the atmosphere is made by these bacteria. Besides this, the microorganisms
      may be very well suited to be applied as an efficient, cost-effective, and
      environmental-friendly alternative to conventional wastewater treatment for the
      removal of nitrogen. So far, nine different anammox species divided over five
      genera have been enriched, but none of these are in pure culture. This number is
      only a modest reflection of a continuum of species that is suggested by 16S rRNA
      analyses of environmental samples. In their environments, anammox bacteria thrive
      not just by competition, but rather by delicate metabolic interactions with other
      N-cycle organisms. Anammox bacteria owe their position in the N-cycle to their
      unique property to oxidize ammonium in the absence of oxygen. Recent research
      established that they do so by activating the compound into hydrazine (N(2)H(4)),
      using the oxidizing power of nitric oxide (NO). NO is produced by the reduction
      of nitrite, the terminal electron acceptor of the process. The forging of the N-N
      bond in hydrazine is catalyzed by hydrazine synthase, a fairly slow enzyme and
      its low activity possibly explaining the slow growth rates and long doubling
      times of the organisms. The oxidation of hydrazine results in the formation of
      the end product (N(2)), and electrons that are invested both in electron
      transport phosphorylation and in the regeneration of the catabolic intermediates
      (N(2)H(4), NO). Next to this, the electrons provide the reducing power for CO(2)
      fixation. The electron-transport phosphorylation machinery represents another
      unique characteristic, as it is most likely localized on a special cell
      organelle, the anammoxosome, which is surrounded by a glycerolipid bilayer of
      ladder-like ("ladderane") cyclobutane and cyclohexane ring structures. The use of
      ammonium and nitrite as sole substrates might suggest a simple metabolic system,
      but the contrary seems to be the case. Genome analysis and ongoing biochemical
      research reveal an only partly understood redundancy in respiratory systems,
      featuring an unprecedented collection of cytochrome c proteins. The presence of
      the respiratory systems lends anammox bacteria a metabolic versatility that we
      are just beginning to appreciate. A specialized use of substrates may provide
      different anammox species their ecological niche.

PMID- 22633061
TI  - Redox biology of tuberculosis pathogenesis.
AB  - Mycobacterium tuberculosis (Mtb) is one of the most successful human pathogens.
      Mtb is persistently exposed to numerous oxidoreductive stresses during its
      pathogenic cycle of infection and transmission. The distinctive ability of Mtb,
      not only to survive the redox stress manifested by the host but also to use it
      for synchronizing the metabolic pathways and expression of virulence factors, is
      central to its success as a pathogen. This review describes the paradigmatic
      redox and hypoxia sensors employed by Mtb to continuously monitor variations in
      the intracellular redox state and the surrounding microenvironment. Two component
      proteins, namely, DosS and DosT, are employed by Mtb to sense changes in oxygen,
      nitric oxide, and carbon monoxide levels, while WhiB3 and anti-sigma factor RsrA
      are used to monitor changes in intracellular redox state. Using these and other
      unidentified redox sensors, Mtb orchestrates its metabolic pathways to survive in
      nutrient-deficient, acidic, oxidative, nitrosative, and hypoxic environments
      inside granulomas or infectious lesions. A number of these metabolic pathways are
      unique to mycobacteria and thus represent potential drug targets. In addition,
      Mtb employs versatile machinery of the mycothiol and thioredoxin systems to
      ensure a reductive intracellular environment for optimal functioning of its
      proteins even upon exposure to oxidative stress. Mtb also utilizes a battery of
      protective enzymes, such as superoxide dismutase (SOD), catalase (KatG), alkyl
      hydroperoxidase (AhpC), and peroxiredoxins, to neutralize the redox stress
      generated by the host immune system. This chapter reviews the current
      understanding of mechanisms employed by Mtb to sense and neutralize redox stress
      and their importance in TB pathogenesis and drug development.

PMID- 22633062
TI  - What determines the efficiency of N(2)-fixing Rhizobium-legume symbioses?
AB  - Biological nitrogen fixation is vital to nutrient cycling in the biosphere and is
      the major route by which atmospheric dinitrogen (N(2)) is reduced to ammonia. The
      largest single contribution to biological N(2) fixation is carried out by
      rhizobia, which include a large group of both alpha and beta-proteobacteria,
      almost exclusively in association with legumes. Rhizobia must compete to infect
      roots of legumes and initiate a signaling dialog with host plants that leads to
      nodule formation. The most common form of infection involves the growth of
      rhizobia down infection threads which are laid down by the host plant. Legumes
      form either indeterminate or determinate types of nodules, with these groups
      differing widely in nodule morphology and often in the developmental program by
      which rhizobia form N(2) fixing bacteroids. In particular, indeterminate legumes
      from the inverted repeat-lacking clade (IRLC) (e.g., peas, vetch, alfalfa,
      medics) produce a cocktail of antimicrobial peptides which cause
      endoreduplication of the bacterial genome and force rhizobia into a nongrowing
      state. Bacteroids often become dependent on the plant for provision of key
      cofactors, such as homocitrate needed for nitrogenase activity or for branched
      chain amino acids. This has led to the suggestion that bacteroids at least from
      the IRLC can be considered as ammoniaplasts, where they are effectively
      facultative plant organelles. A low O(2) tension is critical both to induction of
      genes needed for N(2) fixation and to the subsequent exchange of nutrient between
      plants and bacteroids. To achieve high rates of N(2) fixation, the legume host
      and Rhizobium must be closely matched not only for infection, but for optimum
      development, nutrient exchange, and N(2) fixation. In this review, we consider
      the multiple steps of selection and bacteroid development and how these alter the
      overall efficiency of N(2) fixation.

PMID- 22633063
TI  - Modeling the supercritical fluid extraction of essential oils from plant
      materials.
AB  - Different types of mathematical models were applied in the last decade to
      simulate kinetics of supercritical fluid extraction (SFE) of essential oils from
      aromatic plants. Compared to the extraction of fatty oils, modeling of extraction
      of essential oils is more complicated due to their potential fractionation, co
      extraction of less soluble compounds, and stronger effect of flow pattern on
      extraction yield, which is connected with solute adsorption on plant matrix.
      Fitting the SFE models to experimental extraction curves alone usually does not
      enable reliable selection among the models. Major progress was made when detailed
      models for the extraction from glandular structures of plants were developed. As
      the type of glands is characteristic for plant families, the choice of models for
      SFE of essential oils is substantially facilitated. As the extracts from aromatic
      plants contain also cuticular waxes and other less soluble substances, and
      essential oils themselves are mixtures of substances of different solubility in
      supercritical carbon dioxide, modeling of extraction of mixtures and their
      fractionation in time deserves more attention.

PMID- 22633064
TI  - Gas chromatography-mass spectrometry of hexafluoroacetone derivatives: First time
      utilization of a gaseous phase derivatizing agent for analysis of
      extraterrestrial amino acids.
AB  - Within the perspective of the current and next space missions to Mars (MSL 2011
      and Exomars 2016-2018), the detection and enantioselective separation of building
      blocks such as the amino acids are important subjects which are becoming
      fundamental for the search for traces of life on the surface and subsurface of
      Mars. In this work, we have developed and optimized a method adapted to space
      experimentation to derivatize and analyze amino acids, using hexafluoroacetone as
      the derivatizing agent. The temperature, duration of the derivative transfer to
      the analyser, and chromatographic separation parameters have been optimized to
      meet the instrument design constraints imposed on devices for extraterrestrial
      experiments. The work presented in this rationale has established that
      hexafluoroacetone, in addition to its intrinsic qualities, such as the production
      of light-weight derivatives (no racemization) and great resistance to the drastic
      operating conditions, has indeed facilitated simple and fast derivatization that
      appears to be suitable for in situ analysis in space. By using hexafluoroacetone
      as the derivatizing agent, we successfully identified, 21 amino acids including
      12 of the 20 proteinic amino acids without stirring or extraction steps. Ten of
      these derivatized amino acids were enantioselectively separated. The precision
      and accuracy measurements for the D/L ratio showed that the proposed method was
      also suitable for the determination of both enantioselective forms of most of the
      tested amino acids. The limits of detection obtained were lower than the ppb
      level of organic molecules detected in Martian meteorites.

PMID- 22633065
TI  - Polymeric micelle as the pseudostationary phase in electrokinetic chromatography.
AB  - A simple, green, and novel approach to prepare polymeric micelle with amphiphilic
      random copolymer P (MMA-co-MAA) via neutralization in aqueous medium has been
      developed, and the polymeric micelle was firstly applied as a pseudostationary
      phase (PSP) in electrokinetic chromatography (EKC) in the present work. Three
      structurally similar corticosteroids namely hydrocortisone, prednisolone, and
      prednisone were separated with EKC using polymeric micelle as PSP to assess the
      separation performance. The effects of polymeric concentration and pH on micellar
      microstructure including size, morphology, surface charge density and EKC
      performances have been investigated. TEM showed that amphiphilic random
      copolymers were self-assembled via neutralization to form micelles with well
      defined size and shape. The size and shape of the micelle depended on the P (MMA
      co-MAA) concentration and pH. At the concentration of 0.048 mM and pH 9.2, the
      polymeric micelles were of monodispersity and perfect spheres. DLS showed the
      size of micelle was almost equal as polymer concentration in the range of 0.0096
      0.048 mM, and then enlarged sharply at the concentration larger than 0.048 mM.
      However, the zeta potentials of micelle were nearly unchanged. The polymer
      concentration is also the key parameter for EKC separation. Under the optimum
      conditions, three analytes could be baseline separated within 7.4 min. Compared
      with typical MEKC, MEEKC, and MEKC modified with IL ([Bmim]BF4), the developed
      method was more rapid, efficient, and higher selective. The separation mechanism
      using polymeric micelle as PSP was reverse-phase interaction. The actual cosmetic
      samples were analyzed with recoveries between 97.3% and 113%.

PMID- 22633066
TI  - Evaluation of a multiple-mini-interview protocol used as a selection tool for
      entry to an undergraduate nursing programme.
AB  - Whilst an individual's cognitive skills are essential for academic progress, the
      possession of non-cognitive skills, such as empathy and ethical judgement are
      attributes required and valued in those applying to join healthcare programmes
      and by the profession itself. Doubts have been expressed, however, whether final
      selection using traditional interviewing methods serve adequately to reveal these
      key competencies. Kingston University and St George's University of London,
      therefore, have employed the Multiple-Mini-Interview (MMI) system for those
      applying to their BSc Nursing Programme. The MMI comprises a series of interview
      'stations' where candidates respond to scenarios and are assessed on their
      display of required skills/competences. 890 candidates and 82 interviewers
      completed a short questionnaire to gauge their reaction to the concept. There
      were positive responses from candidates with 65% replying that it was "a better
      experience" compared with traditional interviews. Unsolicited comment was
      generally found to refer to restrictions on opportunities to express enthusiasm
      for nursing. Interviewers likewise responded positively with 71% noting "a better
      experience." Unsolicited feedback indicated that some would have preferred to
      have had greater opportunity to discuss nursing issues, with their interviewees.
      It has been agreed that the MMI system of interviewing will be retained and
      further work will include the tracking of students through and into the
      workplace.

PMID- 22633067
TI  - DNA synthesis, assembly and applications in synthetic biology.
AB  - The past couple of years saw exciting new developments in microchip-based gene
      synthesis technologies. Such technologies hold the potential for significantly
      increasing the throughput and decreasing the cost of gene synthesis. Together
      with more efficient enzymatic error correction and genome assembly methods, these
      new technologies are pushing the field of synthetic biology to a higher level.

PMID- 22633068
TI  - High-resolution HLA-DRB1 genotyping in an Australian inclusion body myositis (s
      IBM) cohort: an analysis of disease-associated alleles and diplotypes.
AB  - We performed high-resolution (4-digit) HLA-DRB1 genotyping in an Australian
      cohort of 105s-IBM patients and 189 controls. Our findings showed that whilst the
      strongest association was with the HLA-DRB1*03:01 allele and the HLA
      DRB1*03:01/*01:01 diplotype, HLA-DRB1*01:01 and HLA-DRB1*13:01 are also risk
      alleles. A number of other alleles, HLA-DRB1*04:01, *04:04, *07:01, *09:01,
      *11:01 and *15:01, as well as the HLA-DRB1*03:01/*04:01 and HLA-DRB1*03:01/*07:01
      diplotypes were reduced in s-IBM cases and may be protective. The HLA-DRB1*03:01
      and HLA-DRB1*13:01 alleles also appear to have an influence on the age at onset
      of the disease and severity of muscle weakness. Our findings indicate that the
      influence of HLA-DRB1 in s-IBM is complex and that epistatic interactions at the
      HLA-DRB1 locus contribute both to disease susceptibility and to the clinical
      phenotype.

PMID- 22633069
TI  - The role of cytochrome P4501A activity inhibition in three- to five-ringed
      polycyclic aromatic hydrocarbons embryotoxicity of marine medaka (Oryzias
      melastigma).
AB  - The mode of action of PAHs that causes fish developmental malformations is
      unclear. The embryotoxicity of marine medaka (Oryzias melastigma) was
      investigated after individual exposure to three- to five-ring PAHs Phe, Py, and
      BaP or co-exposure with alpha-ANF for 18 days. We found that the relationships
      between EROD induction and developmental deformities of embryos showed a various
      pattern under different exposure scenarios of Phe, Py, and BaP, which suggested
      possibly different modes of action in determining the developmental toxicities.
      As for co-exposure scenarios of each PAH combined with ANF, it showed potentially
      synergistic effects. The inhibited CYP1A mediated enzyme activity by ANF after co
      exposure did not effectively alleviate developmental toxicity of embryo. It
      showed potentially synergistic effects after co-exposure of marine fish embryos
      to CYP1A inhibitors and PAH-type CYP1A inducers. Heart deformities in the early
      life stages of marine medaka were recommended as a biomarker for indicating the
      extent of PAH pollution.

PMID- 22633059
TI  - Elemental economy: microbial strategies for optimizing growth in the face of
      nutrient limitation.
AB  - Microorganisms play a dominant role in the biogeochemical cycling of nutrients.
      They are rightly praised for their facility for fixing both carbon and nitrogen
      into organic matter, and microbial driven processes have tangibly altered the
      chemical composition of the biosphere and its surrounding atmosphere. Despite
      their prodigious capacity for molecular transformations, microorganisms are
      powerless in the face of the immutability of the elements. Limitations for
      specific elements, either fleeting or persisting over eons, have left an
      indelible trace on microbial genomes, physiology, and their very atomic
      composition. We here review the impact of elemental limitation on microbes, with
      a focus on selected genetic model systems and representative microbes from the
      ocean ecosystem. Evolutionary adaptations that enhance growth in the face of
      persistent or recurrent elemental limitations are evident from genome and
      proteome analyses. These range from the extreme (such as dispensing with a
      requirement for a hard to obtain element) to the extremely subtle (changes in
      protein amino acid sequences that slightly, but significantly, reduce cellular
      carbon, nitrogen, or sulfur demand). One near-universal adaptation is the
      development of sophisticated acclimation programs by which cells adjust their
      chemical composition in response to a changing environment. When specific
      elements become limiting, acclimation typically begins with an increased
      commitment to acquisition and a concomitant mobilization of stored resources. If
      elemental limitation persists, the cell implements austerity measures including
      elemental sparing and elemental recycling. Insights into these fundamental
      cellular properties have emerged from studies at many different levels, including
      ecology, biological oceanography, biogeochemistry, molecular genetics, genomics,
      and microbial physiology. Here, we present a synthesis of these diverse studies
      and attempt to discern some overarching themes.

PMID- 22633070
TI  - Use of aliphatic hydrocarbons to infer terrestrial organic matter in coastal
      marine sediments off China.
AB  - Sediment samples from the marine systems along the coast of China, covering
      Yellow Sea, inner shelf of the East China Sea (ECS) and the South China Sea
      (SCS), were analyzed for n-alkanes and organic carbon. The concentrations of
      Sigman-C(15-35) were 120-1680 ng g(-1) dry weight with an average of 560 ng g(
      1). Short-chain n-alkanes (<C(21)) in Yellow Sea and the SCS were derived from
      mixed bacteria and planktonic sources, while those in the ECS inner shelf were
      mainly of planktonic sources. Long-chain n-alkanes (>C(21)) were mainly derived
      from terrestrial higher plants. Organic carbon deposited into Yellow Sea and
      Southeast Hainan within the SCS was mainly of terrestrial (13-110%; mean: 58%)
      and marine (48-110%; mean: 86%) sources, respectively. On the other hand, organic
      carbon accumulated in the SCS adjacent to the Pearl River Estuary was derived
      from both terrestrial and marine sources.

PMID- 22633071
TI  - [Gap junctional intercellular communication: a new mechanism in pathophysiology
      of migraine with aura. Therapeutic applications].
AB  - Migraine is a common, recurrent and disabling primary headache disorder, which
      affects up to 20% of the population. About a third of patients with migraine have
      attacks with aura, a focal neurological disturbance that manifests itself as
      visual, sensitive or motor symptoms. Cortical spreading depression, a wave of
      electrical activity that moves across the cerebral cortex through neuronal-glial
      cell gap junctions, would be involved in the triggering of migraine aura.
      Moreover, cortical spreading depression activates perivascular trigeminal
      afferents in the neocortex, that through central and peripheral reflex, cause
      inflammatory reaction in the meninges to generate the headache. Tonabersat, a
      novel benzopyran compound, was selected for clinical trial on the basis of its
      inhibitory activity on cortical spreading depression and neurogenic inflammation
      in animal models of migraine. Moreover, tonabersat inhibited trigeminal ganglion
      neuronal-glial cell gap junctions, suggesting that this compound could prevent
      peripheral sensitization within the ganglion. In clinical trial, tonabersat
      showed a preventive effect on attacks of migraine with aura but had no efficacy
      on non-aura attacks and in the acute treatment of migraine. In conclusion,
      neuronal-glial cell gap junctional intercellular communication seems to be
      involved in the pathophysiology of migraine with aura and is emerging as a new
      promising therapeutic target for prophylactic treatment of patients with chronic
      attacks.

PMID- 22633072
TI  - Variation in clinical practice in carotid surgery in nine countries 2005-2010.
      Lessons from VASCUNET and recommendations for the future of national clinical
      audit.
AB  - OBJECTIVES: The aim of the study was to analyse variation in carotid surgical
      practice, results and effectiveness in nine countries. PATIENTS AND METHODS: A
      total of 48,185 carotid endarterectomies (CEAs) and 4602 carotid artery stenting
      (CAS) procedures were included in the comparison. A theoretical effectiveness of
      CEA provision for each country was estimated. RESULTS: 92.6% of the CEAs were
      performed according to the inclusion criteria based on the current European
      recommendations and had a theoretical benefit for the patient. The indication for
      surgery was symptomatic stenosis in 60.1% and this proportion varied between
      31.4% in Italy and 100% in Denmark. The overall combined stroke and death rate in
      symptomatic patients was 2.3%. This varied between rates of 0.9% in Italy and
      3.8% in Norway. The overall combined stroke and death rate in asymptomatic
      patients was 0.9%. It was lowest in Italy at 0.5%, and highest in Sweden at 2.7%.
      We estimated that the stroke prevention rate per 1000 CEAs varied from 72.9 in
      Italy to 130.8 in Denmark. CONCLUSIONS: There is significant variation in
      clinical practice across the participating countries. The theoretical stroke
      prevention potential of CEA seems to vary between participating countries due to
      differences in the inclusion criteria.

PMID- 22633073
TI  - Chest physiotherapy using intrapulmonary percussive ventilation to treat
      persistent atelectasis in hypoxic patients after smoke inhalation.

PMID- 22633074
TI  - High prevalence of qacA/B carriage among clinical isolates of meticillin
      resistant Staphylococcus aureus in Malaysia.
AB  - The minimum inhibitory concentrations (MICs) of 60 meticillin-resistant
      Staphylococcus aureus (MRSA) isolates from Malaysia to three antiseptic agents -
      benzalkonium chloride (BZT), benzethonium chloride (BAC) and chlorhexidine
      digluconate (CHG) - were determined. All isolates had MICs ranging from 0.5 to 2
      mg/L. Antiseptic resistance genes qacA/B and smr were detected in 83.3% and 1.6%
      of the isolates, respectively. Carriage of qacA/B correlated with reduced
      susceptibility to CHG and BAC. This is the first report of the prevalence of
      qacA/B and smr gene carriage in Malaysian MRSA isolates, with a high frequency of
      qacA/B carriage. The presence of these antiseptic resistance genes and associated
      reduced susceptibility to antiseptic agents may have clinical implications.

PMID- 22633076
TI  - WITHDRAWN: The influence of living along the U.S.-Mexico border on unintentional
      drug overdose death, New Mexico (USA), 2005-2009.
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- 22633077
TI  - Visualization and localization of bromotoluene distribution in Hedera helix using
      NanoSIMS.
AB  - Some plants are known as indoor air purifiers. A large number of studies report
      kinetic purification results for an extensive panel of plants, i.e. the pollutant
      concentration (volatile organic compounds, as known as VOC, most of the time) is
      continuously monitored by gas chromatography. However, only a few papers describe
      the mechanisms involved in such processes. This study deals with the use of
      secondary ion mass spectrometry imaging as an efficient tool to locate
      atmospheric pollutant as bromotoluene within the Hedera helix plant (leaf, roots)
      and the substrate on which it was previously grown. Hedera helix plants have been
      placed in a pollution chamber with control of the exposure parameters. Plant and
      soil samples excised were transferred into a fixative solution of glutaraldehyde
      and paraformaldehyde for a few days, were dehydrated using ethanol and were
      embedded with resin. Cross sections were made from the pale brown solids
      obtained. Then, a device using a cathodic pulverization device capable of
      depositing a few nanometers of gold atoms over the sample was used to make the
      surface electronically conductive for the NanoSIMS. Hence, polluted and
      unpolluted samples of Hedera helix and substrates were obtained following a
      careful procedure that allowed for the discrimination between polluted and
      nonpolluted ones. Nanoscale spatial resolution was an invaluable tool (NanoSIMS)
      to achieve this, and proved that VOCs, such as bromotoluene, were actually
      trapped by plants such as Hedera helix.

PMID- 22633075
TI  - Viral and host control of cytomegalovirus maturation.
AB  - Maturation in herpesviruses initiates in the nucleus of the infected cell, with
      encapsidation of viral DNA to form nucleocapsids, and concludes with envelopment
      in the cytoplasm to form infectious virions that egress the cell. The entire
      process of virus maturation is orchestrated by protein-protein interactions and
      enzymatic activities of viral and host origin. Viral tegument proteins play
      important roles in maintaining the structural stability of capsids and directing
      the acquisition of virus envelope. Envelopment occurs at modified host membranes
      and exploits host vesicular trafficking. In this review, we summarize current
      knowledge of and concepts in human cytomegalovirus (HCMV) maturation and their
      parallels in other herpesviruses, with an emphasis on viral and host factors that
      regulate this process.

PMID- 22633078
TI  - Occurrence and behavior of emerging contaminants in surface water and a restored
      wetland.
AB  - Pollution mitigation is an important target for restored wetlands, and although
      there is much information in relation to nutrient removal, little attention has
      been paid to emerging contaminants. This paper reports on the occurrence and
      attenuation capacity of 17 emerging contaminants in a restored wetland and two
      rivers in North-East Denmark. The compounds belong to the groups of
      pharmaceuticals, fragrances, antiseptics, fire retardants, pesticides, and
      plasticizers. Concentrations in surface waters ranged from 2 to 1476 ng L(-1).
      The compounds with the highest concentrations were diclofenac, 2-methyl-4
      chlorophenoxyacetic acid (MCPA), caffeine, and tris(2-chloroethyl) phosphate
      (TCEP). The herbicide concentrations increased after a rain-fall event,
      demonstrating the agricultural run-off origin of these compounds, whereas the
      concentration of the other emerging contaminants was rather conservative. The
      mitigation capacity of the restored wetland for the compounds ranged from no
      attenuation to 84% attenuation (19% on average). Hence, restored wetlands may be
      considered as a feasible alternative for mitigating emerging contaminants from
      river waters.

PMID- 22633079
TI  - The energy balance positively regulates the levels of circulating TNF-related
      apoptosis inducing ligand in humans.
AB  - BACKGROUND & AIMS: Although decreased levels of circulating TRAIL have been
      associated to cardiovascular risk and overall mortality, the mechanisms
      controlling TRAIL levels in physiopathological conditions are currently unknown.
      The aim of the present study was to investigate whether changes in the energy
      intake and insulin sensitivity may influence circulating TRAIL, and to analyze
      potential relationships between circulating TRAIL and changes in fat mass in
      healthy subjects receiving hypocaloric or hypercaloric diets. METHODS: Three
      distinct groups of participants were studied, at the end of a 14-day (n = 9), 35
      day (n = 30) or 60-day (n = 16) period of experimental bed rest to induce insulin
      resistance and during controlled ambulation, after receiving eucaloric,
      hypocaloric or hypercaloric diets. RESULTS: After bed rest conditions, energy
      restriction significantly decreased circulating TRAIL, while overfeeding
      significantly increased TRAIL levels with respect to eucaloric control subjects.
      Moreover, a positive correlation was found between levels of circulating TRAIL
      and energy intake as well as between circulating TRAIL and energy balance, as
      determined by changes in fat mass in these subjects. CONCLUSIONS: Circulating
      levels of TRAIL exhibit a clear-cut positive correlation with the energy intake
      and balance in healthy subjects during experimental physical inactivity.

PMID- 22633080
TI  - Two-month regimen of isoniazid, rifampin and pirazinamid for latent tuberculosis
      infection.

PMID- 22633081
TI  - Continuing professional development for public health: an andragogical approach.
AB  - The UK professional body for public health, the Faculty of Public Health (FPH),
      has a well-established approach towards continuing professional development (CPD)
      for its members and fellows. The FPH approach, initially designed for public
      health physicians, has evolved to meet CPD requirements of a workforce beyond
      that of public health medicine to what is now a multiprofessional public health
      workforce. Despite over 20 years of CPD activity in the field of public health,
      limited literature examines the underlying theoretical principles, or proposes
      the most effective approach to adopt. Public health CPD is a mandatory
      requirement for ongoing practice in many professional groups; it is therefore
      timely to examine theoretical principles and to propose the adoption of an
      andragogical approach to underpin CPD for all disciplines in public health. This
      paper concludes that adopting an andragogical approach to public health CPD,
      supported with critical reflective practice and undertaken in an ethical and
      moral framework, will equip practitioners to be ready to question practice,
      implement innovation and progress, and meet the challenges of a multiprofessional
      public health service.

PMID- 22633082
TI  - Pregnancy-associated inflammatory markers are elevated in pregnant women with
      systemic lupus erythematosus.
AB  - During normal pregnancy a dampening in T cell-mediated immunity is compensated by
      an increased pro-inflammatory activity. Likewise, the autoimmune disease systemic
      lupus erythematosus (SLE) is associated with inflammatory activity and pregnancy
      complications occur frequently in women with SLE. The aim of this study was to
      elucidate how SLE influences the chemokine and cytokine balance during and after
      pregnancy. Blood samples were taken from pregnant women with or without SLE at
      second and third trimester and 8-12 weeks after pregnancy. Cytokines (interleukin
      (IL)-1beta, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, TNF, IFN-gamma and IFN
      alpha), chemokines (CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CCL2/MCP-1, CCL5/RANTES
      and CCL17/TARC), soluble IL-6 receptor (sIL-6R) and soluble glycoprotein 130
      (gp130) were measured in serum using cytometric bead array (CBA) or enzyme-linked
      immunosorbent assay (ELISA). Women with SLE had increased serum concentrations of
      CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10 and IL-10 compared to controls both during
      and after pregnancy. Further, when dividing the patients based on disease
      activity, the women with active disease had the highest levels. Importantly,
      women with SLE seemed to respond to pregnancy in a similar way as controls, since
      the changes of cytokines and chemokines over the course of pregnancy were similar
      but with overall higher levels in the patient group. In conclusion, changes in
      pro- and anti-inflammatory serum components during pregnancy in women with SLE,
      occurring on top of already more pro-inflammatory levels, might increase their
      risk for pregnancy complications and flares. How their children are affected by
      this heightened inflammatory milieu during pregnancy needs further investigation.

PMID- 22633083
TI  - Variable modulation by cytokines and thiazolidinediones of the prototype Th1
      chemokine CXCL10 in anaplastic thyroid cancer.
AB  - Until now, no data are present in literature about the prototype Th1 chemokine (C
      X-C motif) ligand 10 (CXCL10) in anaplastic thyroid cancer (ATC). This study
      aimed to test in "primary human ATC cells" (ANA) vs "normal thyroid follicular
      cells" (TFC): (a) CXCL10 secretion basally and after interferon (IFN)-gamma
      and/or tumor necrosis factor (TNF)-alpha stimulation; (b) peroxisome proliferator
      activated receptor (PPAR)-gamma activation by thiazolidinediones, rosiglitazone
      or pioglitazone, on CXCL10 secretion, on proliferation and apoptosis in ANA. We
      demonstrate that: (a) ANA, but not TFC, produced basally CXCL10, and did so in
      half of cases; (b) IFN-gamma stimulated dose-dependently CXCL10, in ANA and TFC;
      (c) TNF-alpha did not induce CXCL10 secretion, in ANA and TFC; (d) IFN-gamma+TNF
      alpha induced a synergistic but variable release of CXCL10 in the different ANA
      preparations, while it was more reproducible in TFC; (e) rosiglitazone action on
      CXCL10 in ANA was inhibitory in 2/6, stimulatory in 1/6 and nil in 3/6, whereas
      it was inhibitory in TFC; (f) rosiglitazone inhibition of proliferation in ANA
      was not associated with the effect on CXCL10; (g) nuclear factor-kappaB and
      ERK1/2 were basally activated in ANA, increased by IFN-gamma+TNF-alpha, and
      rosiglitazone inhibited that activation. On the whole, the present data first
      show that ANA cells are able to produce CXCL10, basally and under the influence
      of cytokines. However, the pattern of modulation by IFN-gamma, TNF-alpha or
      thiazolidinediones is extremely variable, suggesting that the intracellular
      pathways involved in the chemokine modulation in ATC have different types of
      deregulation.

PMID- 22633084
TI  - Factors associated with the loss of response to infliximab in patients with
      Crohn's disease.
AB  - BACKGROUND AND AIMS: The efficacy of infliximab (IFX) has validated the role of
      TNF-alpha in the immunopathogenesis of Crohn's disease (CD). However, antibodies
      to IFX emerge, which impair its efficacy. This study investigated factor(s)
      associated with the loss of response (LOR) to IFX and how IFX non-responders may
      be treated. METHODS: Seventy-four patients, 36 IFX responders (GI) and 38 with
      LOR (GII) were included. Trough IFX level, CD activity index (CDAI) and
      immunological markers during IFX maintenance therapy were measured. Adsorptive
      granulocyte/monocyte apheresis (GMA) was applied to patients with LOR. RESULTS:
      The durations of CD, 9.3 +/- 5.5 yr and IFX therapy, 3.4 +/- 2.0 yr in GII were
      longer vs GI (P=0.02, P=0.01). Similarly, C-reactive protein (P<0.0001) and CDAI
      (P<0.0001) in GII were higher. The median trough IFX was 4.7 MUg/mL in GI and 8.4
      MUg/mL in GII, while the dose frequency was 8 weeks in GI and 4 weeks in GII.
      Soluble interleukin-2 receptor (sIL-2R) was higher in GII vs GI (P<0.001).
      Seropositive rates of anti-nuclear antibodies (ANA) and circulating immune
      complexes (CIC) in GII were 50.0% and 68.4%, significantly higher vs GI (P<0.05,
      P<0.01). Patients with LOR duration <1.5 yr showed higher CDAI and sIL-2R
      (P<0.05) vs patients with LOR duration <1.5 yr. Fifteen GII patients received GMA
      plus IFX combination and 46.7% responded. IL-10 increased in GMA-responders
      (P<0.05), while CIC and ANA decreased (P=0.0237, P=0.0463). CONCLUSIONS: Patients
      with LOR to IFX had dysregulated immune response despite uncompromised trough IFX
      level. Further, inadequate T-cell differentiation by IFX was suggested. GMA
      appeared to benefit LOR patients by immunoregulation.

PMID- 22633085
TI  - Distribution and bioaccumulation of heavy metals in aquatic organisms of
      different trophic levels and potential health risk assessment from Taihu lake,
      China.
AB  - Aquatic organisms of different trophic levels were taken from Taihu lake. Heavy
      metals (Cu, Zn, Cr, Ni, Cd, Pb) were measured in phytoplankton, zooplankton, in
      two species of zoobenthos, and in eight fish species, as well as in the water
      column and bottom sediments. Results showed that the concentration of Cu and Zn
      for all organisms was much higher than for other metals, and Cd was the lowest in
      all species. Generally, heavy metal concentrations in phytoplankton were higher
      than in zooplankton. In zoobenthos, the concentration in Bellamya sp.(human
      edible snail) was higher than that in Corbiculidae (bivalve). Metal
      concentrations had no significant difference between fish species but tended to
      be higher in predator fish such as Coilia ectenes and Erythroculter ilishaeformis
      than in herbivorous fish. The level of measured metals in Taihu fish was moderate
      low compared with that of fresh water fishes from international results.
      Spatially, metal concentrations in organisms were higher in the north and west
      Taihu lake but lower in south and east lake and this appears to be related to
      river inputs that are heavily influenced by anthropogenic activities. The bio
      concentration factor (BCF) for all aquatic organisms in the food chain indicated
      that it was generally highest in planktons, followed by zoobenthos, and lowest in
      fish. Health risk assessment and comparison with national and international
      standards showed that consumption of aquatic products from the lake was generally
      safe but fishermen were a higher risk group especially through dietary intake of
      Bellamya sp.

PMID- 22633086
TI  - Contemporary nuclear medicine imaging of neuroendocrine tumours.
AB  - Neuroendocrine tumours (NETs) are rare, heterogeneous, and often hormonally
      active neoplasms. Nuclear medicine (NM) imaging using single photon- and positron
      emitting radiopharmaceuticals allows sensitive and highly specific molecular
      imaging of NETs, complementary to anatomy-based techniques, such as computed
      tomography (CT) and magnetic resonance imaging (MRI). Somatostatin-receptor
      scintigraphy is a whole-body imaging technique widely used for diagnosis, staging
      and restaging of NETs. The increasing availability of hybrid single-photon
      emission CT (SPECT)/CT cameras now offers superior accuracy for localization and
      functional characterization of NETs compared to traditional planar and SPECT
      imaging. The potential role of positron-emission tomography (PET) tracers in the
      functional imaging of NETs is also being increasingly recognized. In addition to
      2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG), newer positron-emitting
      radiopharmaceuticals such as (18)F-dihydroxyphenylalanine (DOPA) and (68)Ga
      1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) peptides, show
      promise for the future. This article will summarize the role of current and
      emerging radiopharmaceuticals in NM imaging of this rare but important group of
      tumours.

PMID- 22633087
TI  - Chinese women's motivation to receive future screening: the role of social
      demographic factors, knowledge and risk perception of cervical cancer.
AB  - PURPOSE OF THE RESEARCH: This paper adopted Protection Motivation Theory (PMT) to
      examine Chinese women's knowledge and perceptions of cervical cancer risk and
      factors influencing their motivation to receive future screening. METHODS AND
      SAMPLE: A cross-sectional survey was conducted with 167 Chinese women (142 women
      were willing to receive a screening in the future and 25 women were not) in 2007
      to collect women's socio-demographic information and sexual history, perceptions
      related to body health and knowledge about cervical cancer and screening, and
      Protection Motivation Theory measures. KEY RESULTS: The majority of women stated
      they intended to receive future screening and response efficacy was significantly
      associated with their intention. However, no significant association was observed
      between sexual history and protection motivation. Using multivariate analysis,
      cancer in relatives (odds ratio, OR = 9.97, 95% CI [1.44-436.3], p = 0.010), a
      perception that visiting a doctor regularly is important to health (OR = 9.85,
      95% CI [1.61-999.9], p = 0.009)), and ever attending for cervical screening
      during the previous three years (OR = 3.49, 95% CI [1.23-11.02], p = 0.016) were
      significantly associated with women' motivation to receive future screening.
      CONCLUSION: The findings of this study highlight the important role of women's
      beliefs in the value of cervical screening and previous screening experience in
      motivating them to receive a screening. Education intervention is needed to
      provide information and raise public awareness about the importance of cervical
      screening to women's health. Culture-related beliefs and social motivational
      processes in addition to those specified by PMT need to be addressed.

PMID- 22633088
TI  - Adenocarcinoma of the esophagus and esophagogastric junction in patients older
      than 70 years: results of neoadjuvant radiochemotherapy followed by transthoracic
      esophagectomy.
AB  - AIM: The standard treatment of locally-advanced esophageal adenocarcinoma
      consists of neoadjuvant radiochemotherapy followed by surgical resection. Very
      little data are available concerning the feasibility of this strategy in patients
      older than 70 years of age. PATIENTS AND METHODS: Between 1996 and 2008, 118
      patients underwent transthoracic esophagectomy with lymphadenectomy for
      adenocarcinoma of the esophagus and gastric cardia (Siewert I and II). These were
      divided into three groups for comparison: Group I (age less than 70 years,
      neoadjuvant treatment followed by surgery; n=66); Group II (age greater or equal
      to 70 years, surgery alone; n=32); Group III (age greater or equal to 70 years,
      neoadjuvant treatment followed by surgery; n=20). Data concerning comorbidities,
      type of intervention, morbidity, mortality, survival and quality of life were
      analyzed. RESULTS: There was no difference among the three groups with regard to
      comorbidity and preoperative evaluation. The patients in Groups I and III had
      more locally-advanced tumors (P<0.001). There was some disparity between the
      types of surgery proposed. The Lewis-Santy esophagectomy was most commonly used
      (90%, 50%, and 65% respectively). The 90-day mortality was 8%, 15%, and 15%
      respectively. There was no statistically significant difference in the incidence
      of postoperative pulmonary, cardiac, or digestive complications among the three
      groups. No difference was found in 5-year survival and quality of life.
      CONCLUSIONS: Neoadjuvant radiochemotherapy for elderly patients (age above 70
      years) with esophageal adenocarcinoma did not seem to increase postoperative
      morbidity or mortality, nor was there any difference in quality of life, nor any
      effect on survival, no matter what the age of the patient.

PMID- 22633089
TI  - Intestinal anastomosis after laparoscopic total gastrectomy.

PMID- 22633090
TI  - Terminalized mechanical side-to-side anastomoses via laparotomy.

PMID- 22633091
TI  - Bouveret's syndrome. An unusual localization of gallstone ileus.
AB  - This case report describes a 77-year-old male, who presented to the emergency
      room with symptoms of an acute proximal small bowel obstruction. Abdominal CT
      scan with multi-planar reconstructions led to the diagnosis of an intestinal
      obstruction due to impaction of a large gallstone in the second portion of the
      duodenum. The CT scan demonstrated a large cholecysto-duodenal fistula as the
      origin of the gallstone migration. Surgical treatment consisted of milking the
      stone down beyond the ligament of Treitz, where it was removed through a jejunal
      enterotomy. The postoperative course was uncomplicated. No attempt was made to
      repair the choledocho-duodenal fistula at the initial intervention nor
      subsequently, and there have been no complications due to the fistula over 36
      months of follow-up observation.

PMID- 22633092
TI  - Integrins as therapeutic targets.
AB  - Integrins are a large family of molecules that are central regulators in
      multicellular biology. They orchestrate cell-cell and cell-extracellular matrix
      (ECM) adhesive interactions from embryonic development to mature tissue function.
      Diverse human pathologies involve integrin adhesion, including thrombotic
      diseases, inflammation, cancer, fibrosis and infectious diseases. Integrins are
      exciting pharmacological targets because they are exposed on the cell surface and
      are sensitive to pharmacological blockade, but the scale of current efforts
      involving integrin therapeutics continues to surprise. Several therapeutics
      targeting integrins are effective drugs: five have been approved for use in
      clinic, with combined sales of over $1.5 billion in 2010 (based on company
      reports from that year). We gathered information from three major drug-trial
      databases and found that ~260 anti-integrin drugs have entered clinical trials.
      Here we overview integrins as drug targets and focus on cancer.

PMID- 22633093
TI  - Accelerated cellular senescence in the kidney: cause or effect of disease
      progression?

PMID- 22633094
TI  - Treating hepatitis C infection by targeting the host.
AB  - More than 130 million people worldwide are chronically infected with the
      hepatitis C virus (HCV), which can lead to cirrhosis, liver failure, and
      hepatocellular carcinoma. Although recently approved HCV NS3-4A protease
      inhibitors significantly improve treatment response rates, current HCV treatment
      is still frequently limited by side effects and by the low genetic barrier to
      viral resistance against direct-acting antiviral agents. A complementary strategy
      is to target the host cellular factors that support the HCV life cycle. Several
      studies, including RNA interference screens, demonstrated that HCV depends on
      dozens, if not hundreds, of cellular proteins to complete its life cycle. A
      better understanding of the interactions between HCV proteins and host factors
      may help to identify host targets for antiviral therapy. In this review, we
      highlight some of the host factors that are particularly attractive targets for
      the treatment of HCV.

PMID- 22633096
TI  - Accelerated senescence of renal tubular epithelial cells is associated with
      disease progression of patients with immunoglobulin A (IgA) nephropathy.
AB  - The aim of this study is to determine the potential correlation between the
      accelerated senescence of renal tubular epithelial cells (RTECs) and the disease
      progression of patients with immunoglobulin A nephropathy (IgAN). A total of 108
      IgAN patients with different Lee's pathologic grades were enrolled. Additionally,
      18 patients with renal resection were recruited as controls. Cellular senescence
      was evaluated by senescence-associated beta-galactosidase (SA-beta-gal) staining
      and an immunohistochemical analysis of p21 and p16 protein expression. The
      expression of type III collagen (Col III) and fibronectin (FN) in renal
      interstitium and the levels of serum total and low-density lipoprotein (LDL)
      cholesterol, serum creatinine concentration (SCr), and 24-h urinary protein
      excretion were evaluated also. SA-beta-gal staining and the expression of p16 and
      p21 were increased significantly in renal biopsy specimens obtained from grades I
      II IgAN patients compared with controls (P < 0.05). The expression of these
      senescence-associated markers increased gradually with disease progression and
      correlated with the renal morphologic changes and the expression of Col III and
      FN in renal interstitium in IgAN patients. A correlation analysis showed that the
      expressions of p16, p21, and SA-beta-gal staining were associated significantly
      with blood pressure and renal function (P < 0.05), but not with patient age, body
      mass index (BMI), LDL cholesterol level, or 24-h urinary protein value (P >
      0.05). Our results indicated that the RTECs in IgAN patients exhibited features
      of accelerated senescence, which were unrelated to mechanisms associated with
      normal aging. Cellular senescence was associated closely with IgAN disease
      progression, which suggested the accelerated senescence of RTECs may contribute
      to this progression.

PMID- 22633098
TI  - Genetic origin and interaction of the Filipino beta0-thalassemia with Hb E and
      alpha-thalassemia in a Thai family.
AB  - We describe hematologic and molecular characteristics of a hitherto undescribed
      interaction between the Filipino deletional beta0-thalassemia with Hb E and alpha
      thalassemia in a Thai family. This study was conducted during the prenatal
      screening of a pregnant Thai woman and her family members. A prenatal diagnosis
      was performed at her second pregnancy by amniocentesis. Laboratory investigations
      identified that the pregnant woman was Hb E heterozygote with alpha+-thalassemia,
      whereas her husband was a double heterozygote for the Filipino deletional beta0
      thalassemia and alpha+-thalassemia. Their affected son was a patient with a
      previously undescribed condition of Hb E-beta0-thalassemia with alpha+
      thalassemia. Both a combined gap-polymerase chain reaction (PCR) and allele
      specific PCR were used successfully in the prenatal diagnosis, which identified
      an affected fetus with Hb E-beta0-thalassemia without alpha+-thalassemia. Beta
      globin gene haplotype analysis indicated the same origin of this Filipino beta0
      thalassemia in Asian populations.

PMID- 22633097
TI  - Erythromycin ameliorates cigarette-smoke-induced emphysema and inflammation in
      rats.
AB  - The exposure to cigarette smoke (CS) is associated with emphysema. In addition to
      chronic lung inflammation, emphysema is known mainly for the complex pathogenesis
      associated with imbalance of proteolytic and antiproteolytic activities,
      oxidative stress, and apoptosis of lung structural cells. Increasing evidence
      shows that erythromycin, which is a macrolide antibiotic, ameliorates chronic
      inflammation via mechanisms independent of its antibacterial activity. We
      hypothesize that erythromycin protects against CS-induced emphysema and
      inflammation in rats via its anti-inflammation and antiapoptosis action. Sprague
      Dawley (SD) rats were administered lipopolysaccharide (LPS) intratracheally
      solution twice and exposed to the CS, the control rats were administered saline
      intratracheally and exposed to ambient air for 3 weeks. Then, all the CS rats
      were distributed randomly into 3 groups and, respectively, treated orally with
      saline (LPS + CS + saline), Guilongkechuanning capsule (450 mg/kg) (LPS + CS +
      GLKCN), or erythromycin (100 mg/kg) (LPS + CS + ERY) 0.5 h before CS exposure for
      2 weeks. On day 36, the rats were killed. The cytokines in serum were measured by
      enzyme-linked immunosorbent assay (ELISA). The middle lobe of the right lung was
      removed for histology and apoptosis analyses, respectively. Emphysematous lesions
      and inflammatory cell infiltrations in the CS group were evident by a histologic
      analysis. Erythromycin protected significantly against the alveolar enlargement
      levels (P = 0.0017), reduced the pathologic apoptosis (P = 0.0023) related with
      Bcl-2 (P = 0.0002) and Bax (P = 0.0002), and inhibited the expressions of matrix
      metalloproteinase (MMP)-9 (P = 0.0019) and TIMP-1 protein (P = 0.04) and the MMP
      9/TIMP-1 ratio (P = 0.0002) in the lungs of CS-induced emphysema in rats. The
      protective effect of erythromycin on CS-induced emphysema and inflammation in
      rats is associated with a reduction in inflammation, imbalance of MMP-9/TIMP-1,
      and apoptosis of lung structural cells. However, erythromycin did not recover
      completely the emphysematous morphologic changes to the levels when compared with
      control rats. This distinctive pattern implies that erythromycin might have the
      potential to suppress airway inflammation and maintain the integrity of airway
      epithelium to some extent.

PMID- 22633099
TI  - Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B
      activation in experimental nonalcoholic steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) is associated with increased liver-related
      mortality. Disturbances in hepatic lipid homeostasis trigger oxidative stress and
      inflammation (ie, lipotoxicity), leading to the progression of NASH. This study
      aimed at identifying whether silibinin may influence the molecular events of
      lipotoxicity in a mouse model of NASH. Eight-week-old db/db mice were fed a
      methionine-choline deficient (MCD) diet for 4 weeks and treated daily with
      silibinin (20 mg/kg intraperitoneally) or vehicle. Liver expression and enzyme
      activity of stearoyl-CoA desaturase-1 and acyl-CoA oxidase, and expression of
      liver fatty acid-binding protein were assessed. Hepatic levels of reactive oxygen
      species, thiobarbituric acid-reactive substances (TBARS), 3-nitrotyrosine (3-NT),
      inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NFkB)
      activities were also determined. Silibinin administration decreased serum alanine
      aminotransferase and improved liver steatosis, hepatocyte ballooning, and lobular
      inflammation in db/db mice fed an MCD diet. Gene expression and activity of
      stearoyl-CoA desaturase-1 were reduced in db/db mice fed an MCD diet compared
      with lean controls and were increased by silibinin; moreover, silibinin treatment
      induced the expression and activity of acyl-CoA oxidase and the expression of
      liver fatty acid-binding protein. Vehicle-treated animals displayed increased
      hepatic levels of reactive oxygen species and TBARS, 3-NT staining, and iNOS
      expression; silibinin treatment markedly decreased reactive oxygen species and
      TBARS and restored 3-NT and iNOS to the levels of control mice. db/db mice fed an
      MCD diet consistently had increased NFkB p65 and p50 binding activity; silibinin
      administration significantly decreased the activity of both subunits. Silibinin
      treatment counteracts the progression of liver injury by modulating lipid
      homeostasis and suppressing oxidative stress-mediated lipotoxicity and NFkB
      activation in experimental NASH.

PMID- 22633095
TI  - Translational research in infectious disease: current paradigms and challenges
      ahead.
AB  - In recent years, the biomedical community has witnessed a rapid scientific and
      technologic evolution after the development and refinement of high-throughput
      methodologies. Concurrently and consequentially, the scientific perspective has
      changed from the reductionist approach of meticulously analyzing the fine details
      of a single component of biology to the "holistic" approach of broadmindedly
      examining the globally interacting elements of biological systems. The emergence
      of this new way of thinking has brought about a scientific revolution in which
      genomics, proteomics, metabolomics, and other "omics" have become the predominant
      tools by which large amounts of data are amassed, analyzed, and applied to
      complex questions of biology that were previously unsolvable. This enormous
      transformation of basic science research and the ensuing plethora of promising
      data, especially in the realm of human health and disease, have unfortunately not
      been followed by a parallel increase in the clinical application of this
      information. On the contrary, the number of new potential drugs in development
      has been decreasing steadily, suggesting the existence of roadblocks that prevent
      the translation of promising research into medically relevant therapeutic or
      diagnostic application. In this article, we will review, in a noninclusive
      fashion, several recent scientific advancements in the field of translational
      research, with a specific focus on how they relate to infectious disease. We will
      also present a current picture of the limitations and challenges that exist for
      translational research, as well as ways that have been proposed by the National
      Institutes of Health to improve the state of this field.

PMID- 22633100
TI  - Effect of oxidative stress and endotoxin on human serum albumin in brain-dead
      organ donors.
AB  - Albumin, among other molecules, binds and detoxifies endotoxin in healthy people.
      Oxidative stress leads to protein oxidation and thus to the impaired binding
      properties of albumin. This property, in combination with increased gut
      permeability, leads to the appearance of endotoxin in the systemic circulation
      and to impaired organ function. We hypothesize that these processes occur in the
      serum of brain-dead organ donors. Endotoxin was determined with an adapted
      Limulus amoebocyte lysate assay. The albumin fractions and binding capacity were
      determined by high-performance liquid chromatography (HPLC). FlowCytomix
      (eBioscience, San Diego, Calif) was used to determine the cytokine levels.
      Carbonylated proteins (CPs) and myeloperoxidase (MPO) were measured by an enzyme
      linked immunosorbent assay (ELISA). Eighty-four brain-dead organ donors were
      enrolled and categorized by the duration of intensive care unit (ICU) stay. The
      albumin-binding capacity for dansylsarcosine was reduced in brain-dead patients
      compared with controls. Endotoxin positivity in 16.7% of donors was associated
      with decreased binding capacity in donors and worse survival of recipients. The
      CP and MPO levels of organ donors were significantly higher than in healthy
      controls. The durations of ICU stay increased albumin oxidation. In addition,
      interleukin-6 (IL-6), IL-8, IL-10, and IL-1beta levels were increased in
      patients, whereas the interferon-gamma (IFN-gamma) levels were within the normal
      range. We conclude that oxidative stress and systemic endotoxemia are present in
      brain-dead organ donors, which might affect recipient survival. High endotoxin
      levels might be caused by increased gut permeability and decreased binding
      capacity of albumin influenced not just by higher albumin oxidation.

PMID- 22633102
TI  - Reply to "Intracardiac T-wave alternans, ischemia, and arrhythmias, in a canine
      model".

PMID- 22633101
TI  - Human umbilical cord blood mononuclear cells activate the survival protein Akt in
      cardiac myocytes and endothelial cells that limits apoptosis and necrosis during
      hypoxia.
AB  - We have previously reported that human umbilical cord blood mononuclear cells
      (HUCBC), which contain hematopoietic, mesenchymal, and endothelial stem cells,
      can significantly reduce acute myocardial infarction size. To determine the
      mechanism whereby HUCBC increase myocyte and vascular endothelial cell survival,
      we treated cardiac myocytes and coronary artery endothelial cells in separate
      experiments with HUCBC plus culture media or culture media alone and subjected
      the cells to 24 h of hypoxia or normoxia. We then determined in myocytes and
      endothelial cells activation of the cell survival protein Akt by Western blots.
      We also determined in these cells apoptosis by annexin V staining and necrosis by
      propidium iodide staining. Thereafter, we inhibited with API, a specific and
      sensitive Akt inhibitor, Akt activation in myocytes and endothelial cells
      cultured with HUCBC during hypoxia and determined cell apoptosis and necrosis. In
      cells cultured without HUCBC, hypoxia only slightly activated Akt. Moreover,
      hypoxia increased myocyte apoptosis by >= 226% and necrosis by 58% in comparison
      with myocytes in normoxia. Hypoxic treatment of endothelial cells without HUCBC
      increased apoptosis by 94% and necrosis by 59%. In contrast, hypoxia did not
      significantly affect HUCBC. Moreover, in myocyte + HUCBC cultures in hypoxia,
      HUCBC induced a >= 135% increase in myocyte phospho-Akt. Akt activation decreased
      myocyte apoptosis by 76% and necrosis by 35%. In endothelial cells, HUCBC
      increased phospho-Akt by 116%. HUCBC also decreased endothelial cell apoptosis by
      58% and necrosis by 42%. Inhibition of Akt with API in myocytes and endothelial
      cells cultured with HUCBC during hypoxia nearly totally prevented the HUCBC
      induced decrease in apoptosis and necrosis. We conclude that HUCBC can
      significantly decrease hypoxia-induced myocyte and endothelial cell apoptosis and
      necrosis by activating Akt in these cells and in this manner HUCBC can limit
      myocardial ischemia and injury.

PMID- 22633103
TI  - Total knee arthroplasty component templating: a predictive model.
AB  - Preoperative planning is essential to total knee arthroplasty (TKA); however, TKA
      templating is historically inaccurate. To improve on templating accuracy and
      streamline preoperative planning, we set out to predict component sizes based on
      patient characteristics without radiographs. A total of 123 consecutive patients
      undergoing unilateral TKA were identified and included in the model study. Input
      variables consisted of age, gender (as a binary number), height, weight, and body
      mass index. A linear regression model was created. The models predicted component
      size exactly in 74% of femurs and 85% of tibias. All model predictions were
      within a +/-1 size of the actual components implanted. Our models were more
      accurate than any previous model for TKA reported.

PMID- 22633104
TI  - Increased revision rates after total knee arthroplasty in patients who smoke.
AB  - The purpose of this study was to compare the clinical outcomes of total knee
      arthroplasty in patients who reported a history of tobacco use with those who
      were nonsmokers. Between 2006 and 2009, there were 131 total knee arthroplasties
      performed in patients who were smokers and 490 in patients who did not smoke. At
      a mean follow-up of 47 months (range, 24-79 months), the patients who were
      smokers had a statistically decreased overall survivorship of 90% (13 revisions)
      compared with 99% (5 revisions) in the nonsmokers. Surgical complication rates
      were not significantly different between the 2 groups; however, there was a
      significant difference in medical complications. Total knee arthroplasty in
      smokers has a higher risk of negative clinical outcomes compared with nonsmokers.

PMID- 22633105
TI  - Patient-reported activity levels after successful treatment of infected total
      knee arthroplasty.
AB  - Infections of total knee replacement can be a devastating complication resulting
      in significant costs to society and healthcare. However, the physical impact to
      patients after successful treatment of these periprosthetic infections remains
      unknown. We performed a retrospective review of 96 patients who had successful
      treatment of their infected total knee replacements with a static antibiotic
      impregnated spacer, and quantified their functional status using the University
      of California Los Angeles (UCLA) activity scale and the Knee Society Scores
      (KSS). Patients reported residual pain and continued disability (KSS pain = 42.0,
      functional = 43.0) after successful treatment. The average UCLA activity score
      was 3.4, which correlated to patients returning to limited activities of daily
      living. Age, sex, and American Society of Anesthesiologist class had no
      significant impact on the UCLA or KSS scores. These results can be used to help
      manage patient expectations after successful treatment of these periprosthetic
      knee infections.

PMID- 22633106
TI  - Introduction. "small steps" in our battle with SCLC.

PMID- 22633107
TI  - Systemic issues in small cell lung cancer.

PMID- 22633109
TI  - Fourier Transform Rheology as an innovative morphological characterization
      technique for the emulsion volume average radius and its distribution.
AB  - This article extends previous works on emulsion characterization via Fourier
      Transform Rheology. The interest here is on the effects of (i) polydispersity and
      (ii) high volume fraction (often associated with commercial samples) on the
      nonlinear rheological behavior. To analyze the effects of polydispersity on the
      LAOS measurements, the investigated samples were characterized with respect to
      their volume average radius, [R](43), and the polydispersity index of the
      distribution. As the nonlinear mechanical emulsion value E(0) introduced in the
      literature is a function of both nonlinear rheological parameters, such as
      I(5/3), as well as emulsion properties including the volume average radius,
      interfacial tension and viscosities of the matrix and dispersed phase, it is,
      therefore, a useful tool for emulsion characterization. In addition, the analysis
      of the higher harmonic ratios, I(7/5), has been demonstrated to provide
      information about the width of the distribution. With respect to the
      characterization of the high volume fraction samples, these first experiments on
      commercial w/o-emulsions were shown to relate nonlinear rheological properties to
      the droplet size and droplet size distribution of highly filled systems,
      demonstrating that LAOS experiments can give useful insights on the average
      droplet size and its distribution.

PMID- 22633108
TI  - Treatment outcome of nasopharyngeal carcinoma with retropharyngeal lymph nodes
      metastasis only and the feasibility of elective neck irradiation.
AB  - OBJECTIVE: To investigate the outcome of nasopharyngeal carcinoma (NPC) with
      retropharyngeal lymph nodes (RLNs) metastasis only and evaluate the feasibility
      of elective neck irradiation. MATERIALS AND METHODS: This is a retrospective
      study of 119 newly diagnosed non-metastatic NPC patients with RLNs metastasis
      only. All of them received definitive radiotherapy. Eighty nine patients received
      elective neck irradiation to levels II, III, VA and the rest received whole neck
      irradiation, including levels II-V. RESULTS: The median follow-up was 36.6
      months. The 5-year local recurrence-free survival (LFS), nodal recurrence-free
      survival (NFS), distant metastasis-free survival (DMFS) and overall survival (OS)
      was 81.4%, 92.7%, 91.8%, and 93.6%, respectively. Four patients developed nodal
      relapse and only one was out-of-field relapse. No significant difference of nodal
      recurrence was observed between elective neck irradiation and whole neck
      irradiation. IMRT or three-dimensional conformal radiotherapy (3D-CRT) showed a
      trend of improving regional control, compared with conventional two-dimensional
      radiotherapy (2D-RT) (p=0.074). In 2D-RT, a higher dose (>5600 cGy) to the upper
      neck showed a benefit of regional control(p=0.006). Multivariate analysis
      demonstrated that only the dose of upper neck was an independent prognostic
      factor of NFS. CONCLUSIONS: Elective irradiation to levels II, III, VA was not
      inferior to whole neck irradiation for NPC patients with RLNs metastasis only.
      However, more evidences are needed to confirm the result. IMRT showed a trend of
      improving regional control. A higher dose of prophylactic radiation may be
      required for upper neck region in patients with RLNs metastasis.

PMID- 22633110
TI  - Plasma polymerized allylamine coated quartz particles for humic acid removal.
AB  - Allylamine plasma polymerization has been used to modify the surface of quartz
      particles for humic acid removal via an inductively coupled rotating barrel
      plasma reactor. Plasma polymerized allylamine (ppAA) films were deposited at a
      power of 25 W, allylamine flow rate of 4.4 sccm and polymerization times of 5-60
      min. The influence of polymerization time on surface chemistry was investigated
      via X-ray photoelectron spectroscopy (XPS), time of flight secondary ion mass
      spectrometry (ToF-SIMS) and electrokinetic analysis. Acid orange 7
      adsorption/desorption quantified the number of surface amine groups. Humic acid
      removal via ppAA quartz particles was examined by varying pH, removal time, humic
      acid concentration, and particle mass. Increasing the polymerization time
      increased the concentration of amine groups on the ppAA quartz surface, thus also
      increasing the isoelectric point. ToF-SIMS demonstrated uniform distribution of
      amine groups across the particle surface. Greatest humic acid removal was
      observed at pH 5 due to electrostatic attraction. At higher pH values, for longer
      polymerization times, humic acid removal was also observed due to hydrogen
      bonding. Increasing the initial humic acid concentration increased the mass of
      humic acid removed, with longer polymerization times exhibiting the greatest
      increases. Plasma polymerization using a rotating plasma reactor has shown to be
      a successful method for modifying quartz particles for the removal of humic acid.
      Further development of the plasma polymerization process and investigation of
      additional contaminants will aid in the development of a low cost water treatment
      system.

PMID- 22633111
TI  - Identification and bibliometric characterization of research groups in the cardio
      cerebrovascular field, Spain 1996-2004.
AB  - INTRODUCTION AND OBJECTIVES: The abundance of macro-level studies on scientific
      production in the field of biomedicine in Spain only serves to highlight the
      scarcity of micro-level studies reporting on the activity of research groups-the
      basic units of the science and technology system. This lack of information may
      well be explained by the ambiguity inherent in the "research group" concept and
      by the existence of synonymous and homonymous bibliographic signatures that
      confuse the correspondence between these and the real authors. The aim of this
      study is to describe bibliographic production in cardio-cerebrovascular research
      and identify research groups active in the field. METHODS: Using Thomson-Reuters'
      National Citation Report for Spain database and the National Library of Medicine
      Medical Subject Headings thesaurus, we defined the field of cardio
      cerebrovascular research and identified research groups through co-authorship
      analysis supported by the opinions of an expert. Groups were described in terms
      of bibliometric indicators of activity and visibility. RESULTS: Ninety-three
      groups made up of 772 different authors were identified from an initial subset of
      6540 publications on cardio-cerebrovascular research. The groups we identified
      came mainly from the healthcare sector and the universities and were mostly
      located in the autonomous regions of Catalonia and the Community of Madrid. The
      scientific production attributable to the groups presented indicators of
      visibility above the mean for biomedicine. CONCLUSIONS: Collaboration between the
      healthcare sector and the universities dominated cardio-cerebrovascular research,
      although international collaboration rates were poor, standing at levels below
      the mean for biomedicine.

PMID- 22633112
TI  - Inappropriate left ventricular mass in a young population.

PMID- 22633113
TI  - New context and old challenges in the healthcare system.
AB  - The economic crisis cannot conceal the need for transformation of the National
      Health System. The financial difficulties of healthcare systems whose spending is
      growing at a faster rate than the economy have been well known for years. The
      development and diffusion of new technologies, increased use of health services,
      rising drug costs, inflation of prices, and the inefficiency of the system
      explain the new context. The challenges facing the healthcare system are not new:
      address the debt, improve funding, review the list of services, transform the
      governance of the system and provide the institutions with real management
      autonomy. The gravity of the economic situation can be an opportunity to carry
      out the long-awaited changes.

PMID- 22633114
TI  - LOXL1 deficiency in the lamina cribrosa as candidate susceptibility factor for a
      pseudoexfoliation-specific risk of glaucoma.
AB  - PURPOSE: To test the hypothesis that a primary disturbance in lysyl oxidase-like
      1 (LOXL1) and elastin metabolism in the lamina cribrosa of eyes with
      pseudoexfoliation syndrome constitutes an independent risk factor for glaucoma
      development and progression. DESIGN: Observational, consecutive case series.
      PARTICIPANTS: Posterior segment tissues obtained from 37 donors with early and
      late stages of pseudoexfoliation syndrome without glaucoma, 37 normal age-matched
      control subjects, 5 eyes with pseudoexfoliation-associated open-angle glaucoma,
      and 5 eyes with primary open-angle glaucoma (POAG). METHODS: Protein and mRNA
      expression of major elastic fiber components (elastin, fibrillin-1, fibulin-4),
      collagens (types I, III, and IV), and lysyl oxidase crosslinking enzymes (LOX,
      LOXL1, LOXL2) were assessed in situ by quantitative real-time polymerase chain
      reaction, (immuno)histochemistry, and light and electron microscopy. Lysyl
      oxidase-dependent elastin fiber assembly was assessed by primary optic nerve head
      astrocytes in vitro. MAIN OUTCOME MEASURES: Expression levels of elastic
      proteins, collagens, and lysyl oxidases in the lamina cribrosa. RESULTS: Lysyl
      oxidase-like 1 proved to be the major lysyl oxidase isoform in the normal lamina
      cribrosa in association with a complex elastic fiber network. Compared with
      normal and POAG specimens, lamina cribrosa tissues obtained from early and late
      stages of pseudoexfoliation syndrome without and with glaucoma consistently
      revealed a significant coordinated downregulation of LOXL1 and elastic fiber
      constituents on mRNA and protein level. In contrast, expression levels of
      collagens and other lysyl oxidase isoforms were not affected. Dysregulated
      expression of LOXL1 and elastic proteins was associated with pronounced
      (ultra)structural alterations of the elastic fiber network in the laminar beams
      of pseudoexfoliation syndrome eyes. Inhibition of LOXL1 interfered with elastic
      fiber assembly by optic nerve head astrocytes in vitro. CONCLUSIONS: The findings
      provide evidence for a pseudoexfoliation-specific elastinopathy of the lamina
      cribrosa resulting from a primary disturbance in LOXL1 regulation and elastic
      fiber homeostasis, possibly rendering pseudoexfoliation syndrome eyes more
      vulnerable to pressure-induced optic nerve damage and glaucoma development and
      progression.

PMID- 22633116
TI  - [Pelvic congestion syndrome: outcome after embolization with coils].
AB  - OBJECTIVE: To study the clinical manifestations and findings at venography in
      patients with pelvic congestion syndrome and to evaluate the outcome after
      percutaneous embolization using coils. MATERIALS AND METHODS: We studied 34 women
      referred to the vascular radiology unit from the vascular surgery department for
      clinical suspicion of pelvic congestion syndrome. All patients underwent
      venography to assess the competence of the ovarian veins and to detect other
      varicose pelvic veins. When pelvic varicose veins were detected, they were
      embolized with coils. Clinical outcomes were recorded after reviewing the
      clinical history and administering a questionnaire over the phone. RESULTS: In 22
      of the 34 patients, signs of pelvic venous insufficiency were found. The symptoms
      were mainly pelvic and perineal heaviness (20/22) and pelvic pain (18/22). The
      technical success of venography and embolization was 100%, with three minor
      complications that did not require hospitalization. Pelvic heaviness improved in
      14 patients (in 13 it was completely eliminated). Pain disappeared in 11 patients
      and was partially alleviated in another 2. CONCLUSION: In patients with pelvic
      congestion syndrome, the embolization of insufficient pelvic veins achieves
      clinical improvement with short hospital stays and few complications.

PMID- 22633117
TI  - Nursing students' understanding of critical thinking and appraisal and academic
      writing: a descriptive, qualitative study.
AB  - In Sweden, regulations from the National Agency for Higher Education advocate an
      education that equips students with independence as well as critical, problem
      based thinking, i.e. academic literacy skills. However, some research findings
      indicate that students may leave higher education without mastering these skills
      effectively. As part of quality-assuring a nursing programme at a university
      college in south-east Sweden we explored the nursing student's view of crucial
      academic literacy skills, such as critical thinking and appraisal and academic
      writing, by conducting a descriptive, qualitative study. Informants were
      recruited through an advertisement posted on the university's e-learning tool.
      Eight focused interviews were conducted during autumn 2010. The transcribed
      interviews were analysed - inspired by content analysis - and two categories
      became apparent: constantly questioning and formality before substance. The
      latter revealed a gap between the student's perception of academic writing and
      that of the educators, thus implying that nursing students might not be equipped
      with the tools they need to develop within academia. We suggest that students
      could benefit in their academic endeavours from theoretical educational models
      that integrate several academic skills simultaneously and which could be
      incorporated into the development of syllabuses and curriculums.

PMID- 22633115
TI  - Cocaine use during pregnancy and health outcome after 10 years.
AB  - BACKGROUND: Women who used cocaine during pregnancy may become at risk for
      increased physical and mental health problems. METHODS: Three hundred and twenty
      one (158 cocaine use during pregnancy (PC), 163 no cocaine (NC)) women were
      assessed using the Health Survey Questionnaire (SF-36V2) 10 years after infant
      birth. Factors related to mental and physical health, and co-occurring with PC,
      were evaluated using multiple regression. RESULTS: Controlling for age and
      education, PC women reported poorer total perceived mental health (PMH) (46.3+/
      .9 vs. 50.7+/-.9, p<.001), more bodily pain (48.1+/-1.0 vs. 51.5+/-1.0, p<.02)
      and poorer health perceptions (46.8+/-.9 vs. 49.7+/-.9, p<.03) than NC women. PC
      women had lower BMI (29% vs. 32%, p<.006), higher current alcoholic drinks
      per/week (4.05+/-15.5 vs. 1.29+/-3.51, p<.005) and number of cigarettes per day
      (9+/-10.6 vs. 4+/-6.5, p<.0001) and greater total life strain (Family Inventory
      of Life Events and Changes (FILE)) (4.6+/-4.9 vs. 3.2+/-3.2, p<.004) than NC
      women. Regression analyses indicated that body mass index (BMI) mediated the
      effect of prior cocaine use on perceived physical health (PPH) and total life
      strain had additive effects. Current cigarette use and total life stress
      partially mediated the effects of cocaine use on PMH and also had additive
      independent effects. CONCLUSIONS: PC use is a marker for poor health after 10
      years. Mediators of these relationships (BMI, stressful life events and current
      tobacco use) should be considered when designing interventions to promote health.

PMID- 22633118
TI  - The Objective Structured Clinical Examination (OSCE) as a strategy for assessing
      clinical competence in midwifery education in Ireland: a critical review.
AB  - In Ireland, to register as a midwife, all student midwives must be deemed
      competent to practice with the assessment of competence an essential component of
      midwifery education. A variety of assessment strategies, including observed
      practice, clinical interviews, portfolios of reflection, the Objective Structured
      Clinical Examination (OSCE) and written examination papers, are utilised to
      assess midwifery students' clinical competence. In this paper, a critical review
      of the OSCE as a strategy for assessing clinical competence in one third level
      institution in Ireland is offered. Although utilised for assessing competence
      across a range of areas (e.g. obstetric emergencies and pharmacology/drug
      administration), the use of the OSCE for assessing midwifery students' competence
      in lactation and infant feeding practices, as an example for this paper, is
      described. The advantages, disadvantages, validity and reliability of the OSCE,
      as an assessment strategy, are critically explored. Recognising that no single
      assessment strategy can provide all the information required to assess something
      as complex as clinical performance, the OSCE, when viewed alongside other forms
      of assessment, and with relevance to the topic under examination, may be
      considered a valuable strategy for enhancing the assessment of students' clinical
      competence, and for embracing diversity within midwifery education and training.

PMID- 22633119
TI  - Preliminary characterization of the murine membrane reticulocyte proteome.
AB  - The maturation from reticulocyte (immature red blood cell) to erythrocyte (mature
      red blood cell) includes the loss or decreased expression of cell surface
      molecules through exosome formation and secretion. Identifying the molecules lost
      and the molecular events involved is important to our understanding of this final
      stage of erythropoiesis and of diseases where it is deranged. Also, the presence
      of certain cell surface molecules is likely responsible for the invasion of
      certain malaria parasites into reticulocytes. Using a global proteomics approach,
      we identified proteins potentially lost during and/or involved in the
      reticulocyte maturation process. The reticulocyte proteome has not yet been
      published, as previous such studies have focused on the mature erythrocyte.
      Membrane-rich fractions were fractionated by electrophoresis followed by analysis
      with tandem mass spectrometry. Seven hundred forty four proteins were identified
      in the reticulocyte-rich membrane fraction, 192 proteins in the erythrocyte-rich
      membrane fraction, with 157 common to both fractions. Many of the proteins found
      uniquely in the reticulocyte were associated with structures known to be in
      reticulocytes (mitochondria, Golgi). Additional proteins detected are or may be
      specifically involved in vesicle trafficking, a process important in the
      maturation process. A number of unique plasma membrane proteins were also
      identified. These results provide the groundwork for future targeted studies to
      improve our understanding of the mechanism of reticulocyte maturation and the
      role of reticulocytes in disease.

PMID- 22633120
TI  - Synthesis and antimycobacterial activity of some phthalimide derivatives.
AB  - Structurally modified phthalimide derivatives were prepared through condensation
      of phthalic and tetrafluorophthalic anhydride with selected sulfonamides with
      variable yields. All compounds were screened for their antimycobacterium activity
      against Mycobacterium tuberculosis H37Ra (ATCC 25177) using a micro broth
      dilution technique. The fluorinated derivatives (compounds 2c, 2d, 2f and 2h) had
      antimycobacterium activity comparable with classical sulfonamide drugs. The
      minimum inhibitory concentration (MIC) of compounds 2c, 2d, 2f and 2h was greater
      than that of isoniazid (MIC<0.02 MUg/mL) and in vitro activity was greater than
      that of pyrazinamide, another first line antimycobacterium drug (MIC 50-100
      MUg/mL). The new compounds could be considered new lead compounds in the
      treatment of multi-drug resistant tuberculosis.

PMID- 22633121
TI  - BioProfile--extract knowledge from corporate databases to assess cross
      reactivities of compounds.
AB  - In the last 10-15 years, many new technologies and approaches have been
      implemented in research in the pharmaceutical industry; these include high
      throughput screening or combinatorial chemistry, which result in a rapidly
      growing amount of biological assay and structural data in the corporate
      databases. Efficient use of the data from this growing data mountain is a key
      success factor; 'provide as much knowledge as possible as early as possible and
      therefore enable research teams to make the best possible decision whenever this
      decision can be supported by stored data'. Here, an approach which started
      several years ago to obtain as much information as possible out of historical
      assay data stored in the corporate database is described. It will be shown how
      important a careful preprocessing of the stored data is to enhance its
      information. Different possibilities for accessing and to analyzing the
      preconditioned data are in place. Some of will be described in the examples.

PMID- 22633122
TI  - In vitro stability and in vivo anti-inflammatory efficacy of synthetic
      jasmonates.
AB  - A chlorinated methyl jasmonate analog (J7) was elaborated as an in vitro anti
      inflammatory lead. However, its in vitro efficacy profile was not reproduced in a
      subsequent in vivo evaluation, presumably due to its rapid enzymatic hydrolysis
      in a biological system. In an attempt to improve the metabolic stability of the
      lead J7 by replacement of its labile methyl ester with reasonable ester groups,
      several analogs resistant to enzymatic hydrolysis were synthesized. In vivo
      evaluation of the stability-improved analogs showed that these compounds
      displayed higher efficacy than the lead J7, suggesting that these new jasmonate
      analogs may serve as potential anti-inflammatory leads.

PMID- 22633123
TI  - The adjustable nucleosome: an epigenetic signaling module.
AB  - This review examines the proposition that the nucleosome, in addition to its role
      as a DNA packaging device, is a signaling module through which changing
      environmental and metabolic conditions can influence genomic functions. The role
      of enzyme-catalyzed post-translational modifications of the core histones is
      critically assessed, leading to the conclusion that they play varied, often
      crucial and sometimes causative roles in this signaling process.

PMID- 22633124
TI  - Proteomics reveals evidence of cross-talk between protein modifications in
      bacteria: focus on acetylation and phosphorylation.
AB  - Recent advances in gel-free, mass spectrometry-based proteomics have firmly
      established existence of serine phosphorylation, threonine phosphorylation,
      tyrosine phosphorylation and lysine acetylation on many bacterial proteins.
      Intriguingly, numerous proteins have been shown to be modified by both
      modifications, leading to the emerging concept of cross-talk between
      posttranslational modifications in bacteria. This concept is further supported by
      biological follow-up studies that are starting to reveal bacterial proteins and
      processes regulated by multiple modifications. In this review, we provide an
      overview of the large-scale studies involving protein phosphorylation and
      acetylation in bacteria and discuss some of the current examples of cross-talk
      between these and other bacterial modifications.

PMID- 22633125
TI  - Carbonate horizons, paleosols, and lake flooding cycles: Beds I and II of Olduvai
      Gorge, Tanzania.
AB  - This study documents the petrology and stable isotope geochemistry of carbonates
      from six horizons from Beds I and II of Olduvai Gorge, Tanzania. The studied
      succession, immediately below and above Tuff IF, consists of interbedded waxy and
      earthy claystones with discrete carbonate horizons and thin sandstones. The
      succession was deposited in response to repeated flooding and withdrawal of a
      saline-alkaline lake. The carbonates and their overlying disconformities are
      important because they help define the surfaces on which hominin activity took
      place and allow very high-resolution correlation of geographically separated
      levels of hominin exploitation. The range of different carbonates includes
      unambiguous land-surface and pedogenic features including calcified rootmat
      horizons, rhizocretions, and micritic nodules, together with less determinate
      sparry calcite nodules. Stellate nodules are interpreted as pseudomorphs after
      sulfate-roses. The carbonate nodules are synsedimentary features, truncated by
      fluvial and other erosional surfaces. The isotopic composition of the carbonates
      is variable with delta(18)O ranging from -7.00/00 to -4.30/00, and delta(13)C
      from -8.50/00 to -1.60/00. A covariant increase in delta(13)C and delta(18)O
      repeats in each carbonate horizon and in individual nodules (inner to outer
      layers): it reflects the evolution of synsedimentary groundwaters. At times of
      low lake level, the carbonates started to precipitate from meteoric waters with
      low isotopic values and continued to form as lake levels rose and the waters
      became increasingly saline. Some of the samples have a last-stage cement of
      strontium rich dolomite, which supports late-stage flooding by the saline
      alkaline lake. Previous studies of carbonate horizons from Olduvai have
      interpreted carbon isotope values in terms of changes in C(3) and C(4) plants
      that colonized the land surface. This study demonstrates that in some instances
      the isotope values from carbonates deposited in these lake marginal settings
      reflect changes in hydrology rather than vegetation.

PMID- 22633126
TI  - Pulmonary artery pressure in cystic fibrosis adults: characteristics, clinical
      correlates and long-term follow-up.
AB  - BACKGROUND: We examined pulmonary artery pressure (PAP) characteristics of CF
      adults, studied clinical correlates and long-term survival. METHODS:
      Comprehensive clinical data were collected and Doppler echocardiography was used
      to estimate PAP in 109 stable CF adults and 50 healthy controls. RESULTS: CF
      patients had lower day and night-time oxygen status, elevated CRP and BNP, and
      elevated PAP (27.7(13.2, 62.8) mmHg patients v 17.9(11.3, 30.9) mmHg controls,
      p<0.001). Even patients with mild pulmonary disease had raised PAP. PAP
      measurements strongly correlated with arterial partial pressure of oxygen
      (PaO(2), r=-0.673, p<0.001), and FEV(1) percentage predicted (FEV(1)%, r=-0.642,
      p<0.001) which were both independent predictors of PAP. At 10 year follow up PAP
      measurements were related to survival but FEV(1)% and PaO(2) were both stronger
      predictors of death. CONCLUSIONS: PAP is raised in CF adults and correlates with
      pulmonary disease severity. Unlike PaO(2) and FEV(1)%, it does not appear to be
      an independent prognostic marker.

PMID- 22633127
TI  - Meta-analysis of screening and case finding tools for depression in cancer:
      evidence based recommendations for clinical practice on behalf of the Depression
      in Cancer Care consensus group.
AB  - BACKGROUND: To examine the validity of screening and case-finding tools used in
      the identification of depression as defined by an ICD10/DSM-IV criterion
      standard. METHODS: We identified 63 studies involving 19 tools (in 33
      publications) designed to help clinicians identify depression in cancer settings.
      We used a standardized rating system. We excluded 11 tools without at least two
      independent studies, leaving 8 tools for comparison. RESULTS: Across all cancer
      stages there were 56 diagnostic validity studies (n=10,009). For case-finding,
      one stem question, two stem questions and the BDI-II all had level 2 evidence
      (2a, 2b and 2c respectively) and given their better acceptability we gave the
      stem questions a grade B recommendation. For screening, two stem questions had
      level 1b evidence (with high acceptability) and the BDI-II had level 2c evidence.
      For every 100 people screened in advanced cancer, the two questions would
      accurately detect 18 cases, while missing only 1 and correctly reassure 74 with 7
      falsely identified. For every 100 people screened in non-palliative settings the
      BDI-II would accurately detect 17 cases, missing 2 and correctly re-assure 70,
      with 11 falsely identified as cases. The main cautions are the reliance on DSM-IV
      definitions of major depression, the large number of small studies and the
      paucity of data for many tools in specific settings. CONCLUSIONS: Although no
      single tool could be offered unqualified support, several tools are likely to
      improve upon unassisted clinical recognition. In clinical practice, all tools
      should form part of an integrated approach involving further follow-up, clinical
      assessment and evidence based therapy.

PMID- 22633128
TI  - A diagnostic profile of those who return a false positive assignment on bipolar
      screening measures.
AB  - OBJECTIVES: Our aim was to identify the diagnostic profile of patients classified
      as 'false positives' on two bipolar screening measures; the Mood Swings
      Questionnaire (MSQ) and the Mood Disorders Questionnaire (MDQ). METHODS: A total
      of 1534 patients attending the Black Dog Institute Depression Clinic completed
      the MSQ-46, and a smaller subset of 852 completed the MDQ. All patients underwent
      clinical assessment by one or more Institute psychiatrists. RESULTS: Using
      clinical assignment (i.e. bipolar vs. unipolar) as the criterion measure for
      assessing the screening measures, the overall agreement rates were 84% for the
      MSQ-46 and 74% for the MDQ. Patients identified as 'false positives' were most
      likely to be clinically diagnosed as having a unipolar non-melancholic depression
      (37% for MSQ-46; 46% for MDQ), or a primary anxiety condition with secondary non
      melancholic depression (19% for MSQ-46; 15% for MDQ). In addition, within the
      unipolar non-melancholic group, 46% of the MSQ-46 assigned false positives and
      63% of the MDQ assigned false positives had co-morbid anxiety conditions.
      CONCLUSIONS: These findings suggest that patients with anxiety conditions account
      for a significant proportion of false positive diagnoses on bipolar screening
      tests - a finding that should be conceded in the development and refinement of
      such screening measures and in clinical assessment of the possibility of a
      bipolar disorder.

PMID- 22633129
TI  - Hand position alters vision by biasing processing through different visual
      pathways.
AB  - The present study investigated the mechanisms responsible for the difference
      between visual processing of stimuli near and far from the observer's hands. The
      idea that objects near the hands are immediate candidates for action led us to
      hypothesize that vision near the hands would be biased toward the action-oriented
      magnocellular visual pathway that supports processing with high temporal
      resolution but low spatial resolution. Conversely, objects away from the hands
      are not immediate candidates for action and, therefore, would benefit from a bias
      toward the perception-oriented parvocellular visual pathway that supports
      processing with high spatial resolution but low temporal resolution. We tested
      this hypothesis based on the psychophysical characteristics of the two pathways.
      Namely, we presented subjects with two tasks: a temporal-gap detection task which
      required the high temporal acuity of the magnocellular pathway and a spatial-gap
      detection task that required the spatial acuity of the parvocellular pathway.
      Consistent with our prediction, we found better performance on the temporal-gap
      detection task and worse performance on the spatial-gap detection task when
      stimuli were presented near the hands compared to when they were far from the
      hands. These findings suggest that altered visual processing near the hands may
      be due to changes in the contribution of the two visual pathways.

PMID- 22633130
TI  - In vivo measurement of shoulder joint loads during walking with crutches.
AB  - BACKGROUND: Following surgery or injury of the lower limbs, the use of walking
      aids like crutches can cause high loads on the shoulder joint. These loads have
      been calculated so far with computer models but with strongly varying results.
      METHODS: Shoulder joint forces and moments were measured during crutch-assisted
      walking with complete and partial unloading of the lower limbs. Using
      telemeterized implants in 6 subjects axillary crutches and forearm crutches were
      compared. A force direction was more in the direction of the long humeral axis,
      and slightly lower forces were assumed using axillary crutches. Similar force
      magnitudes as those experienced during previously measured wheelchair weight
      relief tasks were expected for complete unloading. The friction-induced moment
      was hypothesized to act mainly around the medio-lateral axis during the swing
      phase of the body. FINDINGS: Maximum loads of up 170% of the bodyweight and 0.8%
      of the bodyweight times meter were measured with large variations among the
      patients. Higher forces were found in most of the patients using forearm
      crutches. The hypothesized predominant moment around the medio-lateral axis was
      only found in some patients. More often, the other two moments had larger
      magnitudes with the highest values in female patients. The assumed different load
      direction could only be found during partial unloading. INTERPRETATION: In
      general the force magnitudes were in the range of activities of daily living.
      However, the number of repetitions during long-lasting crutch use could lead to
      shoulder problems as a long-term consequence. The slightly lower forces with
      axillary crutches could be caused by loads acting directly from the crutch on the
      scapula, thus bypassing the glenohumeral joint. The higher bending moments in the
      female patients could be a sign of lacking muscle strength for centring the
      humeral head on the glenoid.

PMID- 22633131
TI  - Totally implantable central venous access port infections in patients with
      digestive cancer: incidence and risk factors.
AB  - BACKGROUND: Central venous access port-related bloodstream infection (CVAP-BSI)
      is associated with morbidity and mortality in patients with cancer. This study
      examined the incidence rates and risk factors for CVAP-BSI in adult patients with
      digestive cancer. METHODS: This prospective observational cohort study was
      performed from 2007 to 2011 in 2 oncology units of a university hospital.
      Incidence rate was expressed as number of CVAP-BSI per 1,000 catheter-days. A Cox
      regression model was used to identify risk factors for CVAP-BSI. RESULTS: A total
      of 315 patients were included. CVAP-BSI occurred in 41 patients (13.0%). The
      overall incidence rate was 0.76/1,000 catheter-days. The rate was higher in
      patients with esophageal cancer (1.28. P = .05) and pancreatic cancer (1.24; P =
      .007). Risk factors independently associated with CVAP-BSI were World Health
      Organization performance status between 2 and 4, catheter utilization-days in the
      previous month, pancreatic cancer, and parenteral nutrition. Coagulase-negative
      Staphylococci and enterobacteria were the main microorganisms isolated.
      CONCLUSIONS: In adult patients with digestive cancer, pancreatic cancer,
      cumulative catheter utilization-days, World Health Organization performance
      status, and parenteral nutrition were identified as independent risk factors for
      CVAP-BSI. Patients with any of these risk factors could be candidates for
      preventive strategies.

PMID- 22633132
TI  - Prevalence of and risk factors for needlestick and sharps injuries among nursing
      students in Hong Kong.
AB  - BACKGROUND: Although nursing students are at greater risk for needlestick
      injuries (NSIs) and sharps injuries (SIs) than staff nurses, there is a lack of
      research on NSIs and SIs in students, especially in different years of study. The
      purpose of this study was to identify the risk factors for and prevalence of NSIs
      and SIs among nursing students in different years of study. METHODS: This was a
      cross-sectional survey study using a questionnaire confirmed to be valid and
      reliable, with a content validity index of 0.96 and reliability index of 0.82.
      RESULTS: A total of 878 nursing students (response rate, 76.61%), participated in
      the study. NSIs/SIs, NSIs, and SIs were significantly increased by year of study
      (P < .001) in both the study period and 12-month prevalence. Four predictors for
      NSIs/SIs were final-year study (odds ratio [OR], 11.9; 95% confidence interval
      [CI], 3.9-36.7), perception of not receiving prevention training (OR, 2.8; 95%
      CI, 1.1-7.5), perception of not using a kidney dish to contain used needles and
      sharps (OR, 4.2; 95% CI, 1.7-10.3), and perception of not immediately discarding
      used needles and syringes into a sharps box (OR, 2.9; 95% CI, 1.2-7.4).
      CONCLUSIONS: Preclinical training, reinforcement of kidney dish use, immediate
      discarding of used needles, and adequate clinical supervision are essential
      elements in reducing the risk of NSIs and SIs.

PMID- 22633133
TI  - Health care workers' perceptions predicts uptake of personal protective
      equipment.
AB  - BACKGROUND: Health care workers' (HCW) compliance with infection control measures
      is influenced by organizational, environmental and individual factors. However,
      it is unknown whether HCWs' perceptions of transmission risk and protectiveness
      of infection control measures influences the uptake of infection control
      measures. METHODS: A questionnaire of perceptions and intentions to use infection
      control measures was completed by 74 HCWs at 2 hospitals. HCWs also indicated a 1
      m transmission risk zone and their perceived transmission risk zone. Responses
      were used in logistic regression models to predict intended behaviors. RESULTS:
      Poor recognition of the importance of employing a 1-m transmission risk zone
      predicted intention not to don a mask in single rooms where patient contact was
      unexpected (adjusted odds ratio [AOR], 0.5; P = .032). When contact was expected,
      perceived protectiveness of pre-exposure prophylaxis (AOR, 7.9; P < .001),
      vaccination (AOR, 3.6; P = .023), and a minimum 1-m risk zone (AOR, 9.8; P =
      .022) predicted mask use. HCWs perceived transmission risk zones within 2.45 m
      from attending an adult and 1.12 m from attending pediatric patients. CONCLUSION:
      Intention to use a facemask was poor for care in single rooms but improved if
      patient contact was expected and in multibed rooms. HCWs attending pediatric
      patients measured a smaller transmission risk zone than what is currently
      recommended under droplet precautions.

PMID- 22633134
TI  - Automated hand hygiene count devices may better measure compliance than human
      observation.
AB  - BACKGROUND: Hand hygiene is considered a critical factor in the prevention of
      health care-associated infections, and there have been many studies on ways to
      measure hand hygiene compliance. OBJECTIVE: Our objective was to evaluate the
      utility of estimating hand hygiene compliance using automated count technology
      versus direct human observation before and after a feedback intervention. We used
      a before and after quasi-experimental study over 30 weeks, in the setting of one
      12-bed neurocare intensive care unit (NCICU) and one 15-bed cardiac intensive
      care unit (CCU) in a university, tertiary care hospital. METHODS: We assessed
      hand hygiene through a quasi-experimental study comparing estimated compliance
      using automated count technology and direct observation by a secret shopper with
      a feedback intervention at month 3. We used Poisson segmented regression and
      chi(2) tests to compare trends before and after the intervention. RESULTS: Over
      30 weeks, we collected 424,682 dispenser counts and 338 hours of human
      observations that included 1,783 room entries. Electronic hand hygiene dispenser
      counts increased significantly in the post-intervention period relative to the
      pre-intervention period (average count/patient-day increased 22.7 in the NCICU
      and 7.3 in the CCU, both P < .001), but direct observation of compliance did not
      change significantly (percent compliant increased by 2.9% in the NCICU and
      decreased by 6.7% in the CCU, P = .47 and P = .07, respectively). CONCLUSION:
      Passive electronic monitoring of hand hygiene dispenser counts does not closely
      correlate with direct human observation and was more responsive than observation
      to a feedback intervention.

PMID- 22633135
TI  - Phonological storage and executive function deficits in children with mathematics
      difficulties.
AB  - Children with mathematics difficulties suffer from working memory deficits. This
      study investigated the deficit profile of phonological storage and executive
      functions in working memory among children with mathematics difficulties. Based
      on multiple instruments and two assessment points, 68 children were screened out
      of 805 fifth graders. Of these 68 children, 18 were classified as children with
      only mathematics difficulties (MD), 20 were classified as children with
      mathematics and reading difficulties (MDRD), and 30 were typically developing
      (TD) peers matched on age and general ability. Measures for phonological storage,
      dual-task performance, inhibition, and updating of verbal and numerical materials
      were administered individually. Results showed that compared with the TD group,
      children with MD exhibited storage and inhibition deficits specific to numerical
      information and dual-task deficits of both verbal and numerical information,
      whereas children with MDRD showed extensive deficits on phonological storage and
      executive functions on both verbal and numerical tasks. Moreover, executive
      function deficits were not confined to phonological storage deficits.
      Implications of the findings for the working memory deficit profile and working
      memory training among children with mathematics difficulties were discussed.

PMID- 22633136
TI  - Effect of chondroitin sulfate on turpentine-induced down-regulation of CYP1A2 and
      CYP3A6.
AB  - This study aimed to assess whether chronic administration of chondroitin sulfate
      (CS) affects baseline expression of cytochrome P450 isoforms and impedes the
      decrease in expression and activity of CYP1A2 and CYP3A6 in rabbits with a
      turpentine-induced inflammatory reaction (TIIR). Seven groups of 5 rabbits, 3
      control groups and 4 receiving 20 mg/kg/day of CS for 20 and 30 days, were used.
      The rabbits of 1 control group and 2 groups receiving CS had a TIIR; finally, the
      rabbits of one of the control groups remained in the animal facilities for 30
      days to assess the effect of time and environment on cytochrome P450. In control
      rabbits, intake of CS for 20 and 30 days did not affect CYP3A6, CYP1A2 and NADPH
      cytochrome P450 reductase (CPR) mRNA, protein expression and activity. Compared
      with control rabbits, the TIIR not only reduced mRNA, protein expression and
      activity of CYP3A6 and CYP1A2 but also that of CPR. In rabbits with TIIR, CS
      prevented the decrease of CYP3A6 expression but not the reduction in activity. CS
      did not impede TIIR-induced down-regulation of CYP1A2. Hepatic NO()
      concentrations and NF-kappaB nuclear translocation were increased by the TIIR,
      effect reversed by CS. In vitro, in hepatocytes, CS did not alter the expression
      and activity of CYP3A6, CYP1A2, and CPR. In conclusion, oral CS elicits a
      systemic effect but does not affect CYP1A2, CYP3A6, and CPR in control rabbits,
      although in rabbits with TIIR, CS prevents CYP3A6 protein down-regulation but not
      that of CYP1A2.

PMID- 22633137
TI  - A highly efficient galactokinase from Bifidobacterium infantis with broad
      substrate specificity.
AB  - Galactokinase (GalK), particularly GalK from Escherichia coli, has been widely
      employed for the synthesis of sugar-1-phosphates. In this study, a GalK from
      Bifidobacterium infantis ATCC 15697 (BiGalK) was cloned and over-expressed with a
      yield of over 80 mg/L cell cultures. The k(cat)/K(m) value of recombinant BiGalK
      toward galactose (164 s(-1) mM(-1)) is 296 times higher than that of GalK from E.
      coli, indicating that BiGalK is much more efficient in the phosphorylation of
      galactose. The enzyme also exhibits activity toward galacturonic acid, which has
      never been observed on other wild type GalKs. Further activity assays showed that
      BiGalK has broad substrate specificity toward both sugars and phosphate donors.
      These features make BiGalK an attractive candidate for the large scale
      preparation of galactose-1-phosphate and derivatives.

PMID- 22633138
TI  - The ICU as a hospice--What the benefits and who bears the cost?

PMID- 22633139
TI  - A more sensitive pressure-based index to estimate collateral blood supply in case
      of coronary three-vessel disease.
AB  - With progressive occlusion of a coronary main artery, some anastomotic vessels
      are recruited in order to supply blood to the ischemic region. This collateral
      circulation is an important factor in the preservation of the myocardium until
      reperfusion of the area at risk. An accurate estimation of collateral flow is
      crucial in surgical bypass planning as it alters the blood flow distribution in
      the coronary network and can influence the outcome of a given treatment for a
      given patient. The evaluation of collateral flow is frequently achieved using an
      index based on pressure measurements. It is named Collateral Flow Index (CFI) and
      defined as: (P(w)-P(v))/(P(ao)-P(v)), where P(w) is the pressure distal to the
      thrombosis, P(ao) the aortic pressure and P(v) the central venous pressure. We
      propose here another index, that is more sensitive to the P(w) value and could
      thus describe the role of collateral flow with more precision. We illustrate this
      idea using some clinical pressure measurements in patients with severe coronary
      disease (stenoses on the left branches and total occlusion of the right coronary
      artery).

PMID- 22633140
TI  - Molecular mechanisms underlying maturation and maintenance of the vertebrate
      neuromuscular junction.
AB  - The vertebrate neuromuscular junction (NMJ), a peripheral synapse formed between
      motoneuron and skeletal muscle, is characterized by a protracted postnatal period
      of maturation and life-long maintenance. In neuromuscular disorders such as
      congenital myasthenic syndromes (CMSs), disruptions of NMJ maturation and/or
      maintenance are frequently observed. In particular, defective neuromuscular
      transmission associated with structural and molecular abnormalities at the pre-
      and postsynaptic membranes, as well as at the synaptic cleft, has been reported
      in these patients. Here, we review recent advances in the understanding of
      molecular and cellular events that mediate NMJ maturation and maintenance. The
      underlying regulatory mechanisms, including key molecular regulators at the
      presynaptic nerve terminal, synaptic cleft, and postsynaptic muscle membrane, are
      discussed.

PMID- 22633141
TI  - Sodium dynamics: another key to astroglial excitability?
AB  - Astroglial excitability is largely mediated by fluctuations in intracellular ion
      concentrations. In addition to generally acknowledged Ca2+ excitability of
      astroglia, recent studies have demonstrated that neuronal activity triggers
      transient increases in the cytosolic Na+ concentration ([Na+](i)) in perisynaptic
      astrocytes. These [Na+](i) transients are controlled by multiple Na+-permeable
      channels and Na+-dependent transporters; spatiotemporally organized [Na+](i)
      dynamics in turn regulate diverse astroglial homeostatic responses such as
      metabolic/signaling utilization of lactate and glutamate, transmembrane transport
      of neurotransmitters and K+ buffering. In particular, near-membrane [Na+](i)
      transients determine the rate and the direction of the transmembrane transport of
      GABA and Ca2+. We discuss here the role of Na+ in the regulation of various
      systems that mediate fast bidirectional communication between neurones and glia
      at the single synapse level.

PMID- 22633142
TI  - Value of systematic aetiological investigation in children with sensorineural
      hearing loss.
AB  - Sensorineural hearing loss is the most common form of sensory impairment in
      children. As a precise aetiological diagnosis has major prognostic and management
      implications, it is useful to evaluate the contents of the aetiological
      investigation of sensorineural hearing loss in France. This article presents a
      retrospective review of professional practices by comparing the aetiological
      investigation of hearing loss in children with a cochlear implant and children
      without a cochlear implant. PATIENTS AND METHODS: One hundred and seven children
      under the age of 18 years with unilateral or bilateral sensorineural hearing loss
      attending the paediatric ENT department for the first time between January 2007
      and January 2009 were included in the study. Data from the clinical interview and
      all complementary investigations were analysed. RESULTS: The various aetiologies
      of hearing loss were classified as genetic, acquired, or unknown in each of the
      two populations. Hearing loss was of unknown origin in 52% of the 87 non
      implanted children and 15% of the 20 children with a cochlear implant.
      CONCLUSION: This study demonstrates the heterogeneous practices in terms of
      aetiological investigation of sensorineural hearing loss as a function of the
      target population. A more systematic aetiological investigation was performed in
      children fitted with a cochlear implant, requiring multidisciplinary management.
      This study indicates the need to define a standard aetiological investigation for
      all children with sensorineural hearing loss.

PMID- 22633143
TI  - Full Bayes Poisson gamma, Poisson lognormal, and zero inflated random effects
      models: Comparing the precision of crash frequency estimates.
AB  - In recent years, complex statistical modeling approaches have being proposed to
      handle the unobserved heterogeneity and the excess of zeros frequently found in
      crash data, including random effects and zero inflated models. This research
      compares random effects, zero inflated, and zero inflated random effects models
      using a full Bayes hierarchical approach. The models are compared not just in
      terms of goodness-of-fit measures but also in terms of precision of posterior
      crash frequency estimates since the precision of these estimates is vital for
      ranking of sites for engineering improvement. Fixed-over-time random effects
      models are also compared to independent-over-time random effects models. For the
      crash dataset being analyzed, it was found that once the random effects are
      included in the zero inflated models, the probability of being in the zero state
      is drastically reduced, and the zero inflated models degenerate to their non zero
      inflated counterparts. Also by fixing the random effects over time the fit of the
      models and the precision of the crash frequency estimates are significantly
      increased. It was found that the rankings of the fixed-over-time random effects
      models are very consistent among them. In addition, the results show that by
      fixing the random effects over time, the standard errors of the crash frequency
      estimates are significantly reduced for the majority of the segments on the top
      of the ranking.

PMID- 22633144
TI  - Decision making at extreme altitude: has anyone seen my executive function
      lately?

PMID- 22633145
TI  - Belaya smert: the white death.
AB  - In the late autumn of 1939, shortly after Second World War had commenced, the
      Soviet Union invaded Finland. This act of military aggression, henceforth known
      to history as the Winter War, was ostensibly carried out to secure a buffer state
      and better protect major urban areas such as St. Petersburg (then known as
      Leningrad). The Red Army's attack through the forests of northern Finland was a
      poorly calculated operation-in the little more than 3 months that the conflict
      lasted, the Soviets suffered extensive losses. The hit-and-run tactics of the
      small, winter-savvy Finnish Army resulted in a not significant number of Red Army
      casualties. But from the Soviet perspective, the Finnish soldiers were merely an
      annoyance compared with the real enemy--the environment. Cold injury reached
      epidemic proportions in the Red Army during this short conflict, apparently
      caused in large part by ignorance of environmental realities by the Soviet high
      command. Paradoxically, the Soviets arguably possessed the most extensive and
      sophisticated body of knowledge about cold injury prevention and treatment on
      earth by the late 1930s. There were significant lessons learned by the Soviets
      during the Winter War, however. When Germany invaded the Soviet Union in 1941,
      the Red Army very successfully applied these lessons during 4 years of vicious
      winter battles on the Eastern Front.

PMID- 22633146
TI  - Water turnover and core temperature on Mount Rainier.
AB  - OBJECTIVE: Hydration is an important logistical consideration for persons
      performing in austere environments because water demands must be balanced with
      the burden of carrying water. METHODS: Seven novice climbers participated in a
      study to determine the hydration kinetics and core temperatures associated with a
      successful summit of Mount Rainier. Ingestible radio-equipped thermometer
      capsules were swallowed to monitor core temperature, and an oral dose of
      deuterium (0.12 +/- 0.02 g.kg-1 body weight) was administered to determine
      hydration kinetics. RESULTS: Mean core temperature throughout the 5.5-hour climb
      to Camp Muir (3000 m) was 37.6 +/- 0.3 degrees C. Water turnover was 95.0 +/-
      17.5 mL.kg-1.24 h-1 over the duration of the 43-hour study. There was a trend for
      reduced body mass from before (75.9 +/- 13.0 kg) to after (74.8 +/- 12.5 kg) the
      climb (P = .06), and urine specific gravity increased from before (1.013 +/-
      0.002) to after (1.022 +/- 0.006) the climb (P = .004). CONCLUSIONS: Hydration
      demands of climbing Mount Rainier are highly elevated despite modest fluctuations
      in core temperature. Participants experienced hypohydration but were able to
      maintain sufficient hydration to successfully summit Mount Rainier and return
      home safely.

PMID- 22633147
TI  - CCR9+ T cells contribute to the resolution of the inflammatory response in a
      mouse model of intestinal amoebiasis.
AB  - Analysis of the mechanisms underlying the inflammatory response in amoebiasis is
      important to understand the immunopathology of the disease. Mucosal associated
      effector and regulatory T cells may play a role in regulating the inflammatory
      immune response associated to Entamoeba histolytica infection in the colon. A
      subpopulation of regulatory T cells has recently been identified and is
      characterized by the expression of the chemokine receptor CCR9. In this report,
      we used CCR9 deficient (CCR9(-/-)) mice to investigate the role of the CCR9(+) T
      cells in a murine model of E. histolytica intestinal infection. Intracecal
      infection of CCR9(+/+), CCR9(+/-) and CCR9(-/-) mice with E. histolytica
      trophozoites, revealed striking differences in the development and nature of the
      intestinal inflammatory response observed between these strains. While CCR9(+/+)
      and CCR9(+/-) mice were resistant to the infection and resolved the pathogen
      induced inflammatory response, CCR9(-/-) mice developed a chronic inflammatory
      response, which was associated with over-expression of the cytokines IFN-gamma,
      TNF-alpha, IL-4, IL-6 and IL-17, while IL-10 was not present. In addition,
      increased levels of CCL11, CCL20 and CCL28 chemokines were detected by qRT-PCR in
      CCR9(-/-) mice. E. histolytica trophozoites were identified in the lumen of the
      cecum of CCR9(-/-) mice at seven days post infection (pi), whereas in CCR9(+/+)
      mice trophozoites disappeared by day 1 pi. Interestingly, the inflammation
      observed in CCR9(-/-) mice, was associated with a delayed recruitment of
      CD4(+)CD25(+)FoxP3(+) T cells to the cecal epithelium and lamina propria,
      suggesting that this population may play a role in the early regulation of the
      inflammatory response against E. histolytica, likely through IL-10 production. In
      support of these data, CCR9(+) T cells were also identified in colon tissue
      sections obtained from patients with amoebic colitis. Our data suggest that a
      population of CCR9(+)CD4(+)CD25(+)FoxP3(+) T cells may participate in the control
      and resolution of the inflammatory immune response to E. histolytica infection.

PMID- 22633148
TI  - Direct visualization of the formation of RecA/dsDNA complexes at the single
      molecule level.
AB  - The assembly of RecA on linear dsDNA with ATPgammaS in the reaction was
      elucidated using atomic force microscopy (AFM) on a single-molecule level. It was
      found that assembly generally (~95%) proceeded from a single nucleation site that
      started from one end of the DNA strand. About 5% of the complexes were formed
      starting either from both ends or from the middle of dsDNA strand. In all these
      cases, the RecA coating was contiguous for each region suggesting the binding of
      RecA to DNA is cooperative. The AFM observation provides direct experimental
      evidence to show how RecA binds to linear dsDNA in the presence of ATPgammaS.

PMID- 22633149
TI  - Operability and early outcome in 48 Irish patients with peritoneal malignancy
      treated by surgery and intraperitoneal chemotherapy in a specialized centre.
AB  - BACKGROUND: In selected cases of peritoneal malignancy a novel approach of
      complete macroscopic tumour removal by extensive surgical cytoreduction, combined
      with intraperitoneal chemotherapy, provides a possibility of cure. The experience
      with 48 consecutive Irish cases undergoing laparotomy in a specialized centre is
      reported. PATIENTS AND METHODS: A subset of 48 Irish patients out of a total of
      120 cases with peritoneal malignancy underwent surgery between September 1999 and
      March 2011 in an English National referral centre. Overall 37/48 (77%) had
      appendiceal mucinous tumours with pseudomyxoma peritonei type syndrome. The
      treatment strategy involved macroscopic complete tumour removal (complete
      cytoreduction) combined with intra-operative, intraperitoneal chemotherapy.
      RESULTS: Overall 30/48 (62.5%) had complete cytoreduction, 15/48 (31.3%) had
      major debulking and 3 (4.2%) had laparotomy and biopsy only. The median (range)
      operating time in hours was 9.8 (4.8-16) in the 30 who had complete cytoreduction
      compared with 6.3 (4.5-11) in the 15 who had debulking (p = 0.019). There was no
      post-operative mortality. Overall five year survival for the complete tumour
      removal group was 66% compared with 12% for those only amenable to major
      debulking. CONCLUSION: This novel strategy of cytoreduction combined with
      intraperitoneal chemotherapy is effective in selected patients with peritoneal
      malignancy. The complex surgery is particularly effective for appendiceal tumours
      and provides the only possibility of cure in this challenging disease.

PMID- 22633150
TI  - [Stroke care in the ICU: general supportive treatment. Experts' recommendations].
AB  - The French Society of Intensive Care (SRLF) requested medical experts to publish
      recommendations on the management of stroke in the ICU for adult and pediatric
      patients. The following article describes the underlying evidence used by the
      experts to elaborate recommendations for general supportive treatment. Such
      treatment is fundamental for victims of acute stroke to avoid neurological
      worsening. Oxygen delivery in a normoxic patient is useless. However, if
      saturation is below 92 %, oxygen supplementation is needed. Hyper- and
      hypoglycemia worsen the neurological prognosis. As no glycemic target is known,
      administration of insulin is required for glucose levels higher that 10 mmol/l.
      Body temperature above 37.5 degrees  is associated with poorer outcome. In the
      acute phase of stroke, high blood pressure should not be lowered except in life
      threatening situations, and if so the lowering should be done cautiously. The
      current consensus is to lower blood pressure if the systolic pressure is above
      220 mmHg or if the diastolic pressure is above 120 mmHg for ischemic stroke. For
      hemorrhagic stroke and after thrombolysis, treatment is needed if systolic
      pressure rises above 180 mmHg and if diastolic pressure is above 105 mmHg. Small
      doses of heparin decrease the risk of deep venous thrombosis and pulmonary
      embolism without increasing cerebral bleeding. There is no consensus on the
      treatment of epileptic crises after stroke and no dedicated treatment. Further
      studies are needed to define adequate blood pressure and glycemic target values
      in order to limit secondary worsening after an acute stroke as well as the
      appropriate modalities for the treatment of epilepsy.

PMID- 22633152
TI  - "Axillary recurrences after sentinel lymph node biopsy: a multicentre analysis
      and follow-up of sentinel lymph node negative breast cancer patients".
AB  - INTRODUCTION: The objective of this study was to conduct a multicentre data
      analysis to identify prognostic factors for developing an axillary recurrence
      (AR) after negative sentinel lymph node biopsy (SLNB) in a large cohort of breast
      cancer patients with long follow-up. PATIENTS AND METHODS: The prospective
      databases from different hospitals of clinically node negative breast cancer
      patients operated on between, 2000 and 2002 were analyzed. SLNB was performed and
      pathological analysis done by local pathologists according to national
      guidelines. Adjuvant treatment was given according to contemporary guidelines.
      Multivariate analysis was performed using all available variables, a p-value of
      <0,05 was considered to be significant. RESULTS: A total of 929 patients who did
      not undergo axillary lymph node dissection were identified. After a median follow
      up of 77 (range 1-106) months, fifteen patients developed an isolated AR (AR rate
      1,6%). Multivariate analysis showed that young age (p = 0.007) and the absence of
      radiotherapy (p = 0.010) significantly increased the risk of developing an AR.
      Distant metastasis free survival (DMFS) was significantly worse for patients with
      an AR compared to all other breast cancer patients (p < 0,0001). CONCLUSION: Even
      after long-term follow up, the risk of developing an AR after a negative SLN in
      breast cancer is low. Young age and absence of radiation therapy are highly
      significant factors for developing an axillary recurrence. DMFS is worse for AR
      patients compared to patients initially diagnosed with N0 or N1 disease.

PMID- 22633153
TI  - Escherichia coli ghosts or live E. coli expressing the ferri-siderophore
      receptors FepA, FhuE, IroN and IutA do not protect broiler chickens against avian
      pathogenic E. coli (APEC).
AB  - The aim of this study was to investigate if immunization with the ferri
      siderophore receptors FepA, FhuE, IroN and IutA could protect chickens against
      avian pathogenic Escherichia coli (APEC) infection. The antigens were
      administered as recombinant proteins in the outer membrane (OM) of E. coli strain
      BL21 Star DE3. In a first immunization experiment, live E. coli expressing all 4
      recombinant ferri-siderophore receptors (BL21(L)) were given intranasally. In a
      second immunization experiment, a mixture of E. coli ghosts containing
      recombinant FepA and IutA and ghosts containing recombinant FhuE and IroN was
      evaluated. For both experiments non-recombinant counterparts of the tentative
      vaccines were administered as placebo. At the time of challenge, the IgG antibody
      response for BL21(L) and a mixture of E. coli ghosts containing recombinant FepA
      and IutA and ghosts containing recombinant FhuE and IroN was significantly higher
      in all immunized groups as compared to the negative control groups (LB or PBS)
      confirming successful immunization. Although neither of the tentative vaccines
      could prevent lesions and mortality upon APEC infection, immunization with
      bacterial ghosts resulted in a decrease in mortality from 50% (PBS) to 31% (non
      recombinant ghosts) or 20% (recombinant ghosts) and these differences were not
      found to be significant.

PMID- 22633154
TI  - Determination of celecoxib in human plasma by liquid chromatography-tandem mass
      spectrometry.
AB  - A liquid chromatography-electrospray tandem mass spectrometry method was
      developed and validated to quantitate celecoxib in human plasma. The assay was
      based on protein precipitation with methanol and liquid chromatography on a C18
      column (55 mm * 2 mm, 3 MUm), the mobile phase consisted of methanol-10 mM
      ammonium acetate (75:25, v/v). Quantification was performed by mass spectrometry
      in the multiple reaction monitoring mode with negative electrospray ionization at
      m/z 380->316 and 384->320 for celecoxib and the internal standard celecoxib-D4,
      respectively. The lower limit of quantitation was 7.0 ng/ml using 0.1 ml of
      plasma and linearity was demonstrated up to 1800 ng/ml. Intra-assay and inter
      assay precision expressed by relative standard deviation was less than 4% and
      inaccuracy did not exceed 6% at all levels. The assay was applied to the analysis
      of samples from a pharmacokinetic study.

PMID- 22633155
TI  - Comorbidity and treatment response in pediatric obsessive-compulsive disorder: a
      pilot study of group cognitive-behavioral treatment.
AB  - This pilot study evaluated the effectiveness of group cognitive-behavioral
      treatment (CBT) on treatment outcomes for children and adolescents who presented
      with obsessive-compulsive disorder (OCD) and complex comorbid conditions,
      including depression, attention deficit/hyperactivity disorder and pervasive
      developmental disorders (PDD). Specifically, the impact of comorbidity on
      treatment response rates and remission rates was examined. Forty-three youth
      (aged 7-17) with OCD participated in group family-based CBT. Assessments were
      conducted at pre- and post-treatment and 6 months. Eighty-six percent of youth
      presented with a secondary psychiatric disorder, and 74% presented with a
      tertiary psychiatric condition. Contrary to the expected, comorbidity was not
      associated with poorer treatment outcomes at post-assessment. At longer term
      follow-up (6 months), however, treatment outcomes were poorer for youth with
      multiple comorbid conditions and for those with attention deficit/hyperactivity
      disorder. The finding that group CBT is largely effective for youth with comorbid
      conditions is of clinical and practical significance. Group delivery of CBT
      provides an efficient and cost-effective approach, and alleviates strain on
      services and service providers. Continued efforts are needed to improve long-term
      outcomes for youth with multiple comorbid conditions and attention
      deficit/hyperactivity disorder. Examining treatment response as a function of
      comorbidity with larger clinical samples is important to extend this research.

PMID- 22633156
TI  - Impaired saccadic adaptation in schizophrenic patients with high neurological
      soft sign scores.
AB  - Many motor and cognitive alterations in schizophrenia suggest the involvement of
      the cerebellum. Neurological soft signs (NSS) are frequent in patients with
      schizophrenia and reductions in cerebellar volume have been associated with high
      NSS scores. In this study, we tested saccadic adaptation, a well-characterised
      oculomotor paradigm involving the cerebellum, in schizophrenic patients with high
      NSS scores. We used a backward reactive saccade adaptation task, in which the
      target moves intrasaccadically toward initial fixation, causing the saccade to
      complete with an endpoint error. A group of 12 schizophrenic patients (SZ; DSM
      IV) with high NSS scores was compared to a group of 13 matched healthy controls
      (HC). SZ patients showed lower saccade adaptation than HC. Nevertheless, the time
      course of adaptation was similar for both groups. This study indicates cerebellar
      dysfunction in patients with schizophrenia and high NSS scores. Part of the
      deficit seen in schizophrenia may have a cerebellar origin.

PMID- 22633157
TI  - [Malignant degeneration of chronic ulcer (Marjolin's ulcer) in an old leprosy
      patient].

PMID- 22633158
TI  - Challenges to changing health behaviours in developing countries: a critical
      overview.
AB  - This overview of recent research on health behaviour change in developing
      countries shows progress as well as pitfalls. In order to provide guidance to
      health and social scientists seeking to change common practices that contribute
      to illness and death, there needs to be a common approach to developing
      interventions and evaluating their outcomes. Strategies forming the basis of
      interventions and programs to change behaviour need to focus on three sources:
      theories of behaviour change, evidence for the success and failure of past
      attempts, and an in-depth understanding of one's audience. Common pitfalls are a
      lack of attention to the wisdom of theories that address strategies of change at
      the individual, interpersonal, and community levels. Instead, programs are often
      developed solely from a logic model, formative qualitative research, or a case
      control study of determinants. These are relevant, but limited in scope. Also
      limited is the focus solely on one's specific behaviour; regardless of whether
      the practice concerns feeding children or seeking skilled birth attendants or
      using a latrine, commonalities among behaviours allow generalizability. What we
      aim for is a set of guidelines for best practices in interventions and programs,
      as well as a metric to assess whether the program includes these practices. Some
      fields have approached closer to this goal than others. This special issue of
      behaviour change interventions in developing countries adds to our understanding
      of where we are now and what we need to do to realize more gains in the future.

PMID- 22633159
TI  - The struggle to improve patient care in the face of professional boundaries.
AB  - Professional boundaries make inter-professional communication, collaboration and
      teamwork more challenging and can jeopardise the provision of safe, high quality
      patient care. This in-depth interview study conducted in three UK acute hospital
      organisations in 2003-2004 explored how professional boundaries affected efforts
      to improve routine practice by acute pain services (small specialist teams set up
      to drive improvements in postoperative pain management through education,
      training, standard-setting and audit). The study found that many anaesthetists
      and to a lesser extent nursing staff saw postoperative pain management as a new
      and unjustified addition to their professional role. Professional identities and
      strong fears about the risks of treatments meant that health professionals
      resisted attempts by the acute pain services to standardise practice and to
      change medical and nursing roles in relation to postoperative pain management.
      Efforts by the acute pain services to improve practice were further hindered by
      inter-professional boundaries (between the medical and nursing professions) and
      by intra-professional boundaries (within the medical and nursing professions).
      The inter-professional boundaries led to the acute pain services devoting a
      substantial part of their time to performing a 'go-between' function between
      nurses and doctors. The intra-professional boundaries hindered collaborative
      working among doctors and limited the influence that the acute pain service
      nurses could have on improving the practice of other nurses. Further work is
      needed to address the underlying fears that can lead to resistance around role
      changes and to develop effective strategies to minimise the impact of
      professional boundaries on patient care.

PMID- 22633160
TI  - Minority status and health information search: a test of the social
      diversification hypothesis.
AB  - Group differences in the search of health information were investigated, to test
      the diversification hypothesis that argues that disadvantaged groups in society
      will be more likely to use the Internet and computer mediated communication to
      access health information to compensate for their lack of social capital. Data
      were gathered from a sample of Internet users representative of the percentage of
      minorities in the general population in Israel (n = 1371). The results provide
      partial support for the hypothesis, indicating that in multicultural societies
      disadvantaged groups show greater motivation to use the Internet to access
      medical information than the majority group. We interpreted our findings as
      suggesting that minority groups that do not have access to specialized networks
      use the Internet to overcome their lack of access to specialized information.
      Implications of the finding are discussed.

PMID- 22633161
TI  - Medicalization and pharmaceuticalization at the intersections: Looking backward,
      sideways and forward.
AB  - Medicalization studies have changed dramatically in the past decade in part due
      to the increased attention to the role of pharmaceuticals and the pharmaceutical
      industry in modern life. This review paper explores the relationship between the
      concepts of medicalization and the newly developed terms of pharmaceuticalization
      and the pharmaceuticalization of public health. We show how and why modernist
      thinking limits the terms' utility to explain a world in which both modern and
      postmodern objects and people interact with each other. We provide a framework
      for reconceptualizing and empirically studying these key processes of the 21st
      century.

PMID- 22633162
TI  - A haven of last resort: the consequences of evacuating Florida nursing home
      residents to nonclinical buildings.
AB  - Nursing home administrators (n = 15) and directors of nursing (n = 15) who worked
      in nursing homes during the 2004-2005 Florida hurricane season participated in a
      series of 6 focus groups. The purpose of the focus groups was to explore issues
      faced by nursing home administrators, nurses, and residents during hurricane
      evacuations. A primary finding was that evacuating nursing home residents to
      buildings that are not designed to support nursing activities (e.g., a school
      gymnasium or church) adversely affected resident feeding, sleeping, movement, and
      security. These nonclinical buildings also presented serious occupational health
      concerns for nursing staff members who provided care during emergencies.
      Recommendations for reducing patient and nursing staff injuries for those forced
      to evacuate to a nonclinical building as the result of an emergency event are
      provided.

PMID- 22633163
TI  - "Chilled" pork--Part I: Sensory and physico-chemical quality.
AB  - Chilled meat exportation comprises chilling within 48 h post-mortem to
      temperatures <0  degrees C without freezing and holding under these conditions
      for several weeks. The effects of this ageing on sensory quality of pork are
      unknown and hence the objective of this study was to compare the sensory quality
      of Canadian pork as found in an export (Japan) market and locally. Regardless
      that the Japanese market's quality criteria were met, pork sorted on-line
      differed (P<0.05) from that for the domestic market only for lightness, exudate
      and cooking loss; no differences in intramuscular fat content were observed.
      Overall, a trained panel scored weaker pork and meat flavours and odours in the
      export than the domestic pork as a result of either the quality by selection if
      roasted or the ageing (-1.7  degrees C, 43 days exported chilled or 3.1  degrees
      C, 5 days domestic) if grilled or shabu shabu. Grilled pork was also more tender,
      sweeter and had stronger caramel flavour with the chilled ageing.

PMID- 22633164
TI  - Cutaneous lesion induced by a subcutaneous administration of bortezomib.

PMID- 22633165
TI  - Hairy cell leukemia: allogeneic transplantation could be an optimal option in
      selected patients.

PMID- 22633166
TI  - Adherence to BCR-ABL inhibitors: issues for CML therapy.
AB  - Treatment for chronic myeloid leukemia (CML) has improved substantially in the
      past 20 years, especially since the introduction of oral BCR-ABL inhibitors a
      decade ago. However, for patients to reap the benefits of BCR-ABL inhibitors,
      they must likely receive therapy for the remainder of their lives. In this
      situation, adherence to medication becomes a concern. Adherence to therapy for
      chronic health conditions, including CML, has been demonstrated to be poor.
      Studies have shown nonadherence in CML to be common in one-third or more of
      patients, and 100% adherence is rare. Furthermore, evidence suggests that reduced
      adherence to BCR-ABL inhibitors is associated with reduced efficacy and increased
      healthcare costs. Factors that can cause nonadherence, including dose, toxicity,
      time from diagnosis to prescription, and the number of concomitant medications,
      should be addressed and monitored by the physician. To maximize adherence, CML
      treatment should be individualized to the patient and simplified as appropriate.

PMID- 22633167
TI  - Nilotinib-associated vascular events.
AB  - Anecdotal evidence suggests that nilotinib therapy may be associated with severe
      peripheral artery occlusive disease (PAOD). The authors describe the experience
      at M.D. Anderson Cancer Center regarding vascular events associated with
      nilotinib therapy in patients with chronic myeloid leukemia. Overall, 5 cases of
      PAOD were identified among 233 patients, for an incidence of 2%. Nilotinib is a
      highly selective inhibitor of the inactive conformation of ABL1 kinase. An
      improved topologic fit to the ABL1 protein-binding surface contributes to its
      increased potency over imatinib. This higher selectivity in vitro translated to
      an improved tolerability in vivo. In fact, nilotinib therapy in the frontline
      phase III ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials
      Newly Diagnosed Patients) study was associated with an improved toxicity profile
      compared with that of imatinib. Intriguingly, several cases of severe peripheral
      artery occlusive disease (PAOD) have been reported among patients treated with
      nilotinib in small series. We have identified 5 patients with chronic myeloid
      leukemia (CML) in whom vascular events developed that were likely related to
      nilotinib therapy among 233 (2%) patients treated at our institution: 1 patient
      had recurrent Raynaud syndrome, a second patient had recurrent cerebrovascular
      accidents, and 3 other patients had PAOD (2 of them with other vascular events,
      including coronary artery disease and pulmonary emboli, respectively). Risk
      factors for vascular disease were present in only 1 patient with a history of
      diabetes mellitus. Although the incidence of vascular events is low, this
      potential complication should be taken into account when selecting nilotinib for
      the treatment of CML.

PMID- 22633168
TI  - Association between TGF-beta1-509C/T polymorphism and endometriosis: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To evaluate the association between the transforming growth factor
      beta1 gene-509C/T (TGF-beta1-509C/T) polymorphism and the risk of endometriosis.
      STUDY DESIGN: Relevant studies published before October 2011 were identified by
      searching PubMed and Embase. Studies were selected using prior defined criteria.
      The strength of the relationship between the TGF-beta1-509C/T polymorphism and
      endometriosis risk was assessed by Odds Ratios (ORs). Fixed- or random-effects
      model was calculated according to study heterogeneity. Stratification analysis
      and sensitivity analysis were also conducted. Possible publication bias was
      tested by funnel plots and Egger's test. RESULTS: Of 49 potentially relevant
      studies, six case-control studies were identified in this meta-analysis. The
      integrated result showed that the TGF-beta1-509C/T polymorphism was not
      associated with the endometriosis risk for the allele contrast (T vs. C: OR=1.57,
      95%CI=0.88-2.79), the additive genetic model (T/T vs. C/C: OR=2.96, 95%CI=0.97
      9.10), the dominant genetic model (T/T+T/C vs. C/C: OR=1.80, 95%CI=0.80-4.07) and
      the recessive genetic model (T/T vs. C/C+T/C: OR=1.91, 95%CI=0.89-4.12). In the
      stratified analysis by ethnicity, genotyping method and source of control, no
      significantly association was found. Publication bias was not detected in the
      included studies. CONCLUSIONS: Meta-analyses of the available data showed that
      the association between TGF-beta1-509C/T polymorphism and susceptibility of
      endometriosis was not significant. More studies are needed to elucidate its role
      in endometriosis.

PMID- 22633169
TI  - The effect of ethinyl estradiol and drospirenone-containing oral contraceptives
      upon mucoprotein content of cervical mucus.
AB  - OBJECTIVE: To report the effect of oral contraceptives (OC) on cervical
      mucoprotein content by evaluating quantitatively mucoprotein 1 (MUC1),
      mucoprotein 2 (MUC2), mucoprotein 5AC (MUC5AC) and mucoprotein 5B (MUC5B) levels.
      STUDY DESIGN: This prospective controlled study included 20 women of reproductive
      age who had requested OC. Cervical mucus samples were obtained from the women
      before use of the OC and after 2 months of OC use. The mucus samples were then
      evaluated quantitatively for MUC1, MUC2, MUC5AC and MUC5B by ELISA by using
      specific antibodies. RESULTS: MUC5AC mucoprotein predominated quantitatively both
      before and after OC use. After OC use, compared to before OC use, variable
      increases in the levels of all studied mucoproteins were recorded, but the
      increases in MUC1, MUC2 and MUC5B were statistically significant. The difference
      in the level of MUC2 was remarkable (+54.36 +/- 31.88 ng/mL). CONCLUSION: OC use
      may change the mucoprotein content (especially for MUC2) of cervical mucus and
      thus, may cause a highly viscous pattern of cervical mucus which may enhance the
      contraceptive efficacy of OC pills.

PMID- 22633170
TI  - Mannose-binding lectin codon 54 genetic polymorphism and vaginal protein levels
      in women with gynecologic malignancies.
AB  - OBJECTIVES: Mannose-binding lectin (MBL), an innate immune system component that
      binds to carbohydrates, activates the complement cascade and promotes destruction
      of microorganisms and abnormal cells. We determined whether a polymorphism in the
      MBL gene influences vaginal MBL protein concentrations and the occurrence of
      gynecologic malignancies. STUDY DESIGN: DNA from 289 women seen in a gynecologic
      oncology practice and from 126 healthy women was tested for an MBL codon 54
      single nucleotide polymorphism by polymerase chain reaction and endonuclease
      digestion. Vaginal supernatants from 282 of these women were assayed for MBL
      protein by ELISA. RESULTS: The normal (A,A) genotype was present in 84.1% of 126
      healthy women and 85.3% of 95 women with a benign diagnosis as opposed to 70.0%
      of 70 women with ovarian cancer (p=0.02). The MBL variant allele (allele B)
      frequency was 8.7% in healthy women, 8.4% in women with a benign diagnosis and
      17.1% in women with ovarian cancer (p=0.02). Vaginal MBL protein concentrations
      were highest in women with the A,A genotype, intermediate in A,B heterozygotes
      (p<0.0001) and lowest in B,B homozygotes (p=.0097). CONCLUSION: The MBL 54
      polymorphism and reduction in vaginal MBL concentrations may be a risk factor for
      development of epithelial ovarian cancer.

PMID- 22633171
TI  - Patient goals after incontinence procedures: does the single-incision sling
      satisfy them?
AB  - OBJECTIVE: This study was undertaken to describe short-term postoperative
      achievement of subjective preoperative goals for single-incision MiniArc slings,
      in comparison with tension-free vaginal tape (TVT). METHOD: Patients submitted to
      mid-urethral sling (TVT and MiniArc) procedures for stress urinary incontinence
      (SUI) in two centers were included in this prospective study. Before surgery, the
      patients completed a preoperative open-ended questionnaire, in which they
      described their personal outcomes goals for SUI surgery and the degree of
      severity of their symptoms. At the first postoperative check, they were asked to
      assess the degree to which their goals had been met and the degree of
      postoperative incontinence symptoms; their grade of satisfaction was evaluated
      with IIQ-7, UDI-6 and a 0-10 visual analog scale. RESULTS: One hundred and eight
      patients (TVT n=51, MiniArc n=57) were included in this study. Incontinence
      symptom relief and improvement of quality of life were the most commonly
      described preoperative goals. Six to eight weeks after surgery, 47 patients
      (92.1%) after TVT and 53 (92.9%) women after single-incision slings were
      objectively cured (P=1). After surgery, more than 90% of the patients in both
      groups achieved their preoperative goals. Symptom scores improved significantly
      and were comparable in both groups. CONCLUSION: Our results show that self
      reported achievement of preoperative goals of patients submitted to single
      incision slings are comparable at the first follow-up with patients who have
      undergone the classic mid-urethral sling.

PMID- 22633172
TI  - Inhibition of the keratinolytic subtilisin protease Sub3 from Microsporum canis
      by its propeptide (proSub3) and evaluation of the capacity of proSub3 to inhibit
      fungal adherence to feline epidermis.
AB  - Microsporum canis is a pathogenic fungus that causes a superficial cutaneous
      infection called dermatophytosis, mainly in cats, dogs and humans. Proteolytic
      enzymes have been postulated to be key factors involved in the invasion of the
      stratum corneum and keratinized epidermal structures. Among these proteases, the
      secreted subtilisin protease Sub3 was found to be required for adherence of M.
      canis arthroconidia to feline epidermis. This protease is synthetized as a
      preproenzyme consisting of a signal peptide followed by the propeptide and the
      protease domain. In order to assess whether the enzymatic activity of Sub3 could
      be responsible for the role of the protease in the adherence process, we
      expressed and characterized the propeptide of Sub3 and demonstrated that this
      propeptide is a strong inhibitor of its mature enzyme. This propeptide acts as a
      noncompetitive inhibitor with dissociation constants, K(I) and [Formula: see
      text] of 170 and 130 nM respectively. When tested for its capacity to inhibit
      adherence of M. canis to feline epidermis using an ex vivo adherence model made
      of feline epidermis, the propeptide does not prevent adherence of M. canis
      arthroconidia because it loses its capacity to inhibit rSub3 following a direct
      contact with living arthroconidia, presumably through inactivation by fungal
      membrane-bound proteases.

PMID- 22633173
TI  - Use of topical bovine thrombin in an anti-coagulated rat model of hepatic injury.
AB  - The need for surgical hemostasis in patients treated with anticoagulant
      medications is a concern. This study assessed a bovine-derived topical hemostat
      (FastAct, FA) using a partial hepatectomy hemorrhage model in anticoagulated
      rats. Ninety rats were randomly assigned to receive preoperative heparin,
      warfarin, or nothing (n=30/treatment). Within each treatment group, FA, saline,
      direct pressure (DP), electrocautery, or nothing (n=6/group) was applied to the
      hepatectomy site. Eight additional rats were used for assessment of the
      preoperative anticoagulant regimen. Rats that were not anticoagulated and
      received FA had faster clot times and less hemorrhage than those receiving DP
      (P<0.05). In warfarin-pretreated rats, FA resulted in faster coagulation times
      than saline or DP and less hemorrhage than saline (P<0.05). No differences were
      detected in heparinized rats. Across all groups, rats receiving FA lost less
      blood and formed clots more frequently than saline (P<0.05). FA may be useful to
      treat hemorrhage from hepatic lacerations in anticoagulated patients.

PMID- 22633174
TI  - Otologic Wegener's granulomatosis.

PMID- 22633175
TI  - Hair cortisol level as a retrospective marker of hypothalamic-pituitary-adrenal
      axis activity in horse foals.
AB  - Stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and elevated
      cortisol concentrations in fetal plasma are associated with foal maturity,
      viability and adaptation to independent life. However, non-invasive measurement
      of cortisol in hair samples has not yet been validated in horses. The current
      study developed a radioimmunoassay to analyse cortisol in horse hair and was used
      to measure cortisol hair concentration at birth and at 30 and 60 days of age as a
      retrospective study of HPA axis activity. Cortisol was detectable in the hair of
      foals from birth until 2 months, but decreased with time and varied greatly
      between individuals. Analysis of hair cortisol could be useful for non-invasive
      retrospective studies of HPA axis activity in perinatal horse.

PMID- 22633176
TI  - Serum cardiac troponin I concentrations in naturally occurring myelosuppressive
      and non-myelosuppressive canine monocytic ehrlichiosis.
AB  - The aim of this study was to determine whether serum cardiac troponin I (cTnI)
      concentration measured on admission was associated with the clinical severity of
      canine monocytic ehrlichiosis and was predictive of clinical outcome (death or
      survival) in dogs naturally infected with Ehrlichia canis. Serum cTnI
      concentration was compared among 22 dogs with non-myelosuppressive ehrlichiosis
      (NME), 22 dogs with myelosuppressive ehrlichiosis (ME) and 10 healthy dogs.
      Unlike healthy dogs, 45.5% NME and 59.1% ME dogs had increased cTnI
      concentrations. There was no difference in the frequency of cTnI increase or mean
      cTnI concentrations between the NME and ME groups, whereas mean cTnI
      concentration was significantly lower in healthy dogs. No association was
      established between cTnI concentration on admission and clinical outcome.

PMID- 22633177
TI  - Reliability and validity of a questionnaire to measure consumer knowledge
      regarding safe practices to prevent microbiological contamination in restaurants.
AB  - OBJECTIVE: The objective of this study was to develop a validated and reliable
      questionnaire to measure consumer knowledge regarding safe practices to prevent
      microbiological contamination in restaurants and commercial kitchens. METHODS:
      Non-probabilistic samples of individuals were interviewed in the city of
      Campinas, Brazil. Questionnaire items were elaborated and reviewed. Content and
      construct validity, item analysis, test-retest, and internal consistency were
      developed. RESULTS: The questionnaire content validity index was 96%. The final
      instrument presented 23 items, a satisfactory Kuder-Richardson formula 20 of
      0.66, construct validity (P < .001), and reproducibility (r = 0.77). CONCLUSIONS
      AND IMPLICATIONS: The developed questionnaire can be used to support consumer
      education action.

PMID- 22633178
TI  - Diet and body composition outcomes of an environmental and educational
      intervention among men in treatment for substance addiction.
AB  - OBJECTIVE: To determine the effect of an educational and environmental
      intervention on diet, body mass index, and waist circumference of men in
      substance addiction treatment. METHODS: One hundred three racially/ethnically
      diverse men in 6 urban substance addiction residential treatment facilities in
      Upstate New York participated in weekly nutrition and food classes and food
      environment changes to increase healthful food choices. The main outcomes of this
      controlled, quasi-experimental, pre-post evaluation study were diet, body mass
      index, and waist circumference. RESULTS: Forty-three (42%) participants with
      complete data reported significantly greater intakes of fruits and vegetables,
      lower intakes of calories from sweets and desserts, and a reduction in waist
      circumference (P <= .05) following the intervention, compared to the control
      period. CONCLUSIONS AND IMPLICATIONS: An educational and environmental
      intervention can be effective in promoting positive dietary behavior and reducing
      waist circumference among men in residential treatment. These results need to be
      confirmed in a larger, randomized trial.

PMID- 22633180
TI  - Nuclear spectroscopy for in situ soil elemental analysis: Monte Carlo
      simulations.
AB  - We developed a model to simulate a novel inelastic neutron scattering (INS)
      system for in situ non-destructive analysis of soil using standard Monte Carlo
      Neutron Photon (MCNP5a) transport code. The volumes from which 90%, 95%, and 99%
      of the total signal are detected were estimated to be 0.23 m3, 0.37 m3, and 0.79
      m3, respectively. Similarly, we assessed the instrument's sampling footprint and
      depths. In addition we discuss the impact of the carbon's depth distribution on
      sampled depth.

PMID- 22633179
TI  - Morbidity and mortality of Crimean-Congo hemorrhagic fever in Iraq: cases
      reported to the National Surveillance System, 1990-2010.
AB  - Although Crimean-Congo hemorrhagic fever (CCHF) is endemic in the Middle East,
      its incidence in Iraq has not been well described since the early 1980s. To
      document trends and patterns of CCHF occurrence, we analyzed CCHF case reports
      from Iraq's National Surveillance System in 2010 and aggregate reports from
      previous years. A suspected case was defined as fever, hemorrhagic symptoms and a
      history of animal contact. Serologic testing was conducted for confirmation.
      Between 1998 and 2009, the annual number of confirmed cases ranged from zero to
      six. In 2010, 11 confirmed and 28 suspected cases were reported. The case
      fatality rate was 36% among confirmed cases, 4% among suspected cases. Most
      confirmed cases occurred during a three-week period in a single province. While
      CCHF is uncommon in Iraq, sporadic cases and outbreaks do occur. Surveillance
      could be strengthened by updating the case definition and case investigation
      forms.

PMID- 22633181
TI  - An update on the debated association between ADHD and bipolar disorder across the
      lifespan.
AB  - Diagnostic formulations for attention deficit hyperactivity disorder (ADHD) and
      bipolar disorder (BD) both include symptoms of distractibility, psychomotor
      agitation and talkativeness, alongside associated emotional features
      (irritability and emotional lability). Treatment studies suggest the importance
      of accurate delineation of ADHD and BD. However, boundaries between the two
      disorders are blurred by the introduction of broader conceptualisations of BD.
      This review attempts to elucidate whether associations between ADHD and BD are
      likely to be driven by superficial symptomatological similarities or by a more
      meaningful etiological relationship between the disorders. This is achieved by
      outlining findings on comorbidity, temporal progression of the disorders,
      familial co-variation, and neurobiology in ADHD and BD across the lifespan.
      Longitudinal studies fail to consistently show developmental trajectories between
      ADHD and BD. Comparative research investigating neurobiology is in its infancy,
      and although some similarities are seen between ADHD and BD, studies also
      emphasise differences between the two disorders. However, comorbidity and family
      studies appear to show that the two disorders occur together and aggregate in
      families at higher than expected rates. Furthermore close inspection of results
      from population studies reveals heightened co-occurrence of ADHD and BD even in
      the context of high comorbidity commonly noted in psychopathology. These results
      point towards a meaningful association between ADHD and BD, going beyond
      symptomatic similarities. However, future research needs to account for
      heterogeneity of BD, making clear distinctions between classical episodic forms
      of BD, and broader conceptualisations of the disorder characterised by
      irritability and emotional lability, when evaluating the relationship with ADHD.

PMID- 22633183
TI  - Echocardiographic dilemma: misleading thrombus appearance due to cavitation with
      intravascular hemolysis on a mechanical prosthetic valve.

PMID- 22633184
TI  - Protamine dosage based on two titrations reduces blood loss after valve
      replacement surgery: a prospective, double-blinded, randomized study.
AB  - BACKGROUND: Postoperative hemorrhage following cardiopulmonary bypass in heart
      valve replacement patients may be caused by a mismatch of protamine and heparin.
      We hypothesized that a 2-titration-guided protamine dose would reduce protamine
      heparin mismatch and bleeding in those patients. METHODS: Patients scheduled for
      elective cardiac valve replacement surgery (N = 60) were randomly divided into 3
      groups. All patients received 2 titrations: the first at termination of
      cardiopulmonary bypass and the second at 5 minutes after the initial dose of
      protamine. In the control group, the initial protamine dose was based on the
      heparin dose received; the supplemental protamine dose was empirically
      determined. In the single-titration group, the initial dose was based on the
      first titration, while supplemental dose was empirically determined. In the 2
      titration group, both initial and supplemental doses were based on titrations.
      Bleeding volumes were recorded from the time of first protamine dose to 24 hours
      after surgery. RESULTS: Most patients needed supplemental protamine according to
      second titrations. In the 2-titration group, 12 patients received supplemental
      protamine, whereas only 1 patient in the single-titration group and 6 in the
      control group received supplemental protamine (P = 0.003). The blood loss was
      significantly less in the 2-titration group (526 +/- 131 mL) than in the control
      group (730 +/- 385 mL; P = 0.019). CONCLUSIONS: A higher dosage of protamine
      based on 2 titrations reduced blood loss after surgery, supporting the hypothesis
      that inadequate dosage of protamine contributes to hemorrhage after valve
      replacement surgery.

PMID- 22633185
TI  - Invadopodia: the leading force.
AB  - Metastatic spread of cancer cells is the leading cause of mortality from cancer.
      Metastatic cancer cells must penetrate through several barriers to escape the
      primary tumor and gain entry into the bloodstream in order to spread to other
      tissues. It is believed that invasive cancer cells penetrate these barriers by
      forming specialized F-actin rich protrusions called invadopodia that localize
      matrix degrading activity to cell-substrate contact points. Invadopodia gain
      their protrusive ability by combining the physical force generated by actin
      polymerization with the chemical activity of matrix degradation. Accumulating
      data over the past few years have shed light on the molecular mechanisms as well
      as kinase signaling pathways that regulate the complex process of actin
      polymerization in invadopodia. Here we review some of these mechanisms, the
      signaling pathways that regulate this process, as well as the in vivo relevance
      of invadopodial structures. Understanding the mechanisms that govern invadopodia
      formation and function is an essential step in the prevention of cancer invasion
      and metastasis.

PMID- 22633182
TI  - The National Heart, Lung, and Blood Institute retrovirus epidemiology donor
      studies (Retrovirus Epidemiology Donor Study and Retrovirus Epidemiology Donor
      Study-II): twenty years of research to advance blood product safety and
      availability.
AB  - The Retrovirus Epidemiology Donor Study (REDS), conducted from 1989 to 2001, and
      the REDS-II, conducted from 2004 to 2012, were National Heart, Lung, and Blood
      Institute-funded, multicenter programs focused on improving blood safety and
      availability in the United States. The REDS-II also included international study
      sites in Brazil and China. The 3 major research domains of REDS/REDS-II have been
      infectious disease risk evaluation, blood donation availability, and blood donor
      characterization. Both programs have made significant contributions to
      transfusion medicine research methodology by the use of mathematical modeling,
      large-scale donor surveys, innovative methods of repository sample storage, and
      establishing an infrastructure that responded to potential emerging blood safety
      threats such as xenotropic murine leukemia virus-related virus. Blood safety
      studies have included protocols evaluating epidemiologic and/or laboratory
      aspects of human immunodeficiency virus, human T-lymphotropic virus 1/2,
      hepatitis C virus, hepatitis B virus, West Nile virus, cytomegalovirus, human
      herpesvirus 8, parvovirus B19, malaria, Creutzfeldt-Jakob disease, influenza, and
      Trypanosoma cruzi infections. Other analyses have characterized blood donor
      demographics, motivations to donate, factors influencing donor return, behavioral
      risk factors, donors' perception of the blood donation screening process, and
      aspects of donor deferral. In REDS-II, 2 large-scale blood donor protocols
      examined iron deficiency in donors and the prevalence of leukocyte antibodies.
      This review describes the major study results from over 150 peer-reviewed
      articles published by these 2 REDS programs. In 2011, a new 7-year program, the
      Recipient Epidemiology and Donor Evaluation Study-III, was launched. The
      Recipient Epidemiology and Donor Evaluation Study-III expands beyond donor-based
      research to include studies of blood transfusion recipients in the hospital
      setting and adds a third country, South Africa, to the international program.

PMID- 22633186
TI  - Potential pollutant sources in a Choptank River (USA) subwatershed and the
      influence of land use and watershed characteristics.
AB  - Row-crop and poultry production have been implicated as sources of water
      pollution along the Choptank River, an estuary and tributary of the Chesapeake
      Bay. This study examined the effects of land use, subwatershed characteristics,
      and climatic conditions on the water quality parameters of a subwatershed in the
      Choptank River watershed. The catchments within the subwatershed were defined
      using advanced remotely-sensed data and current geographic information system
      processing techniques. Water and sediment samples were collected in May-October
      2009 and April-June 2010 under mostly baseflow conditions and analyzed for select
      bacteria, nitrate-N, ammonium-N, total arsenic, total phosphorus (TP),
      orthophosphate (ortho-P), and particle-phase phosphorus (PP); n=96 for all
      analytes except for arsenic, n=136, and for bacteria, n=89 (aqueous) and 62
      (sediment). Detections of Enterococci and Escherichia coli concentrations were
      ubiquitous in this subwatershed and showed no correlation to location or land
      use, however larger bacterial counts were observed shortly after precipitation.
      Nitrate-N concentrations were not correlated with agricultural lands, which may
      reflect the small change in percent agriculture and/or the similarity of
      agronomic practices and crops produced between catchments. Concentration data
      suggested that ammonia emission and possible deposition to surface waters
      occurred and that these processes may be influenced by local agronomic practices
      and climatic conditions. The negative correlation of PP and arsenic
      concentrations with percent forest was explained by the stronger signal of the
      head waters and overland flow of particulate phase analytes versus dissolved
      phase inputs from groundwater. Service roadways at some poultry production
      facilities were found to redirect runoff from the facilities to neighboring
      catchment areas, which affected water quality parameters. Results suggest that in
      this subwatershed, catchments with poultry production facilities are possible
      sources for arsenic and PP as compared to catchment areas where these facilities
      were not present.

PMID- 22633187
TI  - Lycopene for the prevention and treatment of benign prostatic hyperplasia and
      prostate cancer: a systematic review.
AB  - BACKGROUND: Prostate cancer is a leading cancer affecting men worldwide. Benign
      prostatic hyperplasia (BPH) is a common disease of the prostate affecting men as
      they age, and a risk factor for developing prostate cancer. Lycopene is a member
      of the carotenoid family, whose strong anti-oxidant properties have been
      hypothesised to assist in the prevention and treatment of BPH and prostate
      cancer. The aim of this systematic review was to examine the effectiveness of
      lycopene for the prevention and treatment of BPH and prostate cancer. METHODS: A
      search of the MEDLINE, EMBASE, AMED (Allied and Complementary Medicine) and the
      Cochrane Library databases was performed for published randomised controlled
      trials (RCTs) comparing lycopene to placebo (or other interventions) for the
      treatment of BPH and prostate cancer. All included studies were assessed for
      methodological quality using the Cochrane Collaboration's risk of bias tool.
      RESULTS: Eight RCTs met the inclusion criteria for this systematic review. All
      included studies were heterogeneous with respect to their design and
      implementation of lycopene. Methodological quality of three studies was assessed
      as posing a 'high' risk of bias, two a 'low' risk of bias and the remaining three
      an 'unclear' risk of bias. Meta-analysis of four studies identified no
      significant decrease in the incidence of BPH (RR (relative risk)=0.95, 95%CI
      0.63, 1.44) or prostate cancer diagnosis (RR=0.92, 95%CI 0.66, 1.29) between men
      randomised to receive lycopene and the comparison group. Meta-analysis of two
      studies indicated a decrease in PSA levels in men diagnosed with prostate cancer,
      who received lycopene (MD (mean difference)=-1.58, 95%CI -2.61, -0.55).
      CONCLUSIONS: Given the limited number of RCTs published, and the varying quality
      of existing studies, it is not possible to support, or refute, the use of
      lycopene for the prevention or treatment of BPH or prostate cancer.

PMID- 22633188
TI  - N-6 and n-3 fatty acid cholesteryl esters in relation to incident stroke in a
      Dutch adult population: a nested case-control study.
AB  - BACKGROUND AND AIMS: There are few prospective studies on fatty acid status in
      relation to incident stroke, with inconsistent results. We assessed the
      associations of plasma n-6 and n-3 PUFA in cholesteryl esters with the risk of
      total stroke and stroke subtypes in Dutch adults. METHODS AND RESULTS: We
      conducted a nested case-control study using data from a population-based cohort
      study in adults aged 20-65 years. Blood sampling and data collection took place
      during 1993-1997 and subjects were followed for 8-13 years. We identified 179
      incident cases of stroke and 179 randomly selected controls, matched on age,
      gender, and enrollment date. Odds ratios (OR) with 95% confidence intervals
      (95%CI) were calculated per standard deviation (SD) increase of PUFA in
      cholesteryl esters using multivariable conditional logistic regression. Cases
      comprised 93 ischemic, 50 hemorrhagic, and 36 unspecified strokes. The n-6 PUFA
      linoleic acid and arachidonic acid contributed ~55% and ~6.5% respectively to
      total plasma fatty acids, whereas the n-3 PUFA alpha-linolenic acid contributed
      ~0.5% and eicosapentaenoic acid plus docosahexaenoic acid (EPA-DHA) ~1.3%. After
      adjustment for confounders, n-6 and n-3 PUFA were not associated with incident
      total stroke or stroke subtypes. The OR (95% CI) for total stroke was 0.95 (0.74
      1.23) per SD increase in linoleic acid and 1.02 (0.80-1.30) per SD increase in
      arachidonic acid. ORs (95% CI) for total stroke were 0.94 (0.72-1.21) for alpha
      linolenic acid and 1.16 (0.94-1.45) for EPA-DHA. CONCLUSION: In the present
      study, plasma n-6 or n-3 fatty acids were not related to incident stroke or
      stroke subtypes.

PMID- 22633189
TI  - Vitamin D receptor activation and prevention of arterial ageing.
AB  - In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and
      mortality rate is higher than in the general population, because of frequently
      concomitant hypertension, peripheral vascular disease, heart failure, vascular
      calcification (VC), diabetes and mineral bone disease. Recently, another
      important factor associated to CV risk in CKD has been deeply investigated:
      vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems
      and tissues and VDR activation is associated to positive effects, resulting in
      better blood pressure control and prevention of diabetic nephropathy.
      Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA),
      calcitriol, is associated to higher serum calcium and phosphate levels, thus
      worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol
      might have ameliorative CV effects. The potential positive impact of the use of
      paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may
      open new paths in the fight against CV disease in CKD patients.

PMID- 22633190
TI  - Quantification of contralateral breast dose and risk estimate of radiation
      induced contralateral breast cancer among young women using tangential fields and
      different modes of breathing.
AB  - PURPOSE: Whole breast irradiation with deep-inspiration breath-hold (DIBH)
      technique among left-sided breast cancer patients significantly reduces cardiac
      irradiation; however, a potential disadvantage is increased incidental
      irradiation of the contralateral breast. METHODS AND MATERIALS: Contralateral
      breast dose (CBD) was calculated by comparing 400 treatment plans of 200 left
      sided breast cancer patients whose tangential fields had been planned on gated
      and nongated CT data sets. Various anatomic and field parameters were analyzed
      for their impact on CBD. For a subgroup of patients (aged <=45 years) second
      cancer risk in the contralateral breast (CB) was modeled by applying the linear
      quadratic model, compound models, and compound models considering dose-volume
      information (DVH). RESULTS: The mean CBD was significantly higher in DIBH with
      0.69 Gy compared with 0.65 Gy in normal breathing (P=.01). The greatest impact on
      CBD was due to a shift of the inner field margin toward the CB in DIBH (mean 0.4
      cm; range, 0-2), followed by field size in magnitude. Calculation with different
      risk models for CBC revealed values of excess relative risk/Gy ranging from 0.48
      0.65 vs 0.46-0.61 for DIBH vs normal breathing, respectively. CONCLUSION:
      Contralateral breast dose, although within a low dose range, was mildly but
      significantly increased in 200 treatment plans generated under gated conditions,
      predominately due to a shift in the medial field margin. Risk modeling for CBC
      among women aged <=45 years also pointed to a higher risk when comparing DIBH
      with normal breathing. This risk, however, was substantially lower in the model
      considering DVH information. We think that clinical decisions should not be
      affected by this small increase in CBD with DIBH because DIBH is effective in
      reducing the dose to the heart in all patients.

PMID- 22633192
TI  - BDNF -270 C>T polymorphisms might be associated with stroke type and BDNF -196
      G>A corresponds to early neurological deficit in hemorrhagic stroke.
AB  - Genetic factors might be involved in stroke prognosis, however the role of brain
      derived neurotrophic factor (BDNF) in stroke recovery is unknown. We have studied
      BDNF -196 G>A and -270 C>T polymorphisms in ischemic and hemorrhagic stroke and
      their impact on stroke prognosis. There was higher occurrence of BDNF -270 CC
      genotype in patients with hemorrhagic than ischemic stroke (96% versus 86%,
      p=0.0495). In hemorrhagic stroke BDNF -196 GG carriers scored better in NIHSS at
      admission (14.23 versus 21.00, p=0.0192) and after 7days (8.60 versus 15.00,
      p=0.0408) of onsets. None of the determined polymorphisms had any impact on 30
      day early outcome in ischemic and hemorrhagic stroke.

PMID- 22633191
TI  - [Portal hypertension: recommendations for evaluation and treatment: consensus
      document sponsored by the Spanish Association for the Study of the Liver (AEEH)
      and the Biomedical Research Network Center for Liver and Digestive
      Diseases(CIBERehd)].

PMID- 22633193
TI  - Expression of CCR7 and CD45RA in CD4+ and CD8+ subsets in cerebrospinal fluid of
      134 patients with inflammatory and non-inflammatory neurological diseases.
AB  - We investigated CD45RA and CCR7 expression in CD4+ and CD8+ subsets of
      cerebrospinal fluid (CSF) lymphocytes, both immediately ex vivo and after
      stimulation, from 134 patients with a variety of inflammatory and non
      inflammatory neurological diseases. Most inflammatory diseases had a higher
      CD4+:CD8+ ratio and higher percentage of effector memory T cells (T(EM)) than non
      inflammatory controls, excluding active infection. Moreover, we found that
      patients with highly elevated cell counts in the CSF tended to have a lower
      percentage of central memory T cells (T(CM)) than patients with low or absent
      pleocytosis, with a concomitant increase in T(EM). We also found that samples
      with elevated IgG index or presence of oligoclonal bands had a significantly
      higher CD4+:CD8+ ratio than normal samples, consistent with increased CD4+ help
      for intrathecal IgG synthesis by B cells.

PMID- 22633194
TI  - Eutopic endometrium from women with endometriosis does not exhibit neurotrophic
      properties.
AB  - The role of neurotrophins in eutopic endometrium from endometriosis-patients was
      investigated in a prospective study using immunofluorescence-staining, Western
      blot and a neuronal growth assay. The nerve growth factor is expressed in primary
      endometrial cell culture from women with and without endometriosis. Western blot
      analysis of endometrial biopsies or uterine fluid from patients with and without
      endometriosis shows no difference in the neurotrophin expression. We could not
      find a difference between patients with and without endometriosis with regards to
      the neurite outgrowth of sensory ganglia when treated with conditioned cultured
      medium or uterine fluid. This result refutes the assumed neurotrophic properties
      of eutopic endometrium of patients with endometriosis.

PMID- 22633195
TI  - Serum level of interleukin-6 in Chinese patients with multiple sclerosis.
AB  - The aim of this study was to investigate the serum concentration of interleukin
      (IL)-6 in patients with relapsing-remitting MS (RR-MS), compare the difference
      between males and females, and explore the correlation between the serum
      concentration of IL-6 and clinical parameters like the current age, the age at
      onset, disease duration, disability (expanded disability status scale, EDSS), and
      the number of relapse. We compared the serum concentration of IL-6 in 39 patients
      with MS and 39 healthy controls matched with sex and age. The serum IL-6
      concentration was measured by FlowCytomix. Compared to healthy controls, both the
      frequency of subjects with detectable level of IL-6 (P=0.005) and the serum
      concentration of IL-6 (P=0.004) were significantly higher in MS patients. When
      data were analyzed by gender, statistical significances between MS patients and
      healthy controls were observed only in females, although the frequency with
      detectable level and the serum concentration of IL-6 were higher in male MS
      patients than male controls. The serum level of IL-6 was found to be
      significantly positively correlated with the number of relapse for female MS
      patients (r(s)=0.511, P=0.009), with the current age for male MS patients
      (r(s)=0.700, P=0.005), and with the age at onset for all MS patients (r(s)=0.351,
      P=0.028). Our results may support that IL-6 is involved in the pathogenesis of MS
      and indicate that differences exist between male and female patients.

PMID- 22633196
TI  - Clinical significance of endoscopic ultrasound for gastric submucosal tumors.
AB  - BACKGROUNDS AND AIMS: Gastric submucosal tumors (SMTs) are often detected during
      routine gastroendoscopy but little is known about their natural history. The aim
      of this study was to evaluate the natural course of gastrointestinal mesenchymal
      tumors (GIMTs) in the stomach. PATIENTS AND METHODS: From October 2001 to
      November 2011, a total of 228 gastric SMTs were evaluated by endoscopic
      ultrasonography (EUS). Based on the findings of EUS and enhanced CT, we diagnosed
      these tumors as lipomas, cysts, aberrant pancreases, extramural compressions, and
      GIMTs. The gastric GIMTs which were examined by EUS twice or more were included
      in this study and the factors associated with an increase in the size of gastric
      GIMTs were analyzed. RESULTS: Fifty GIMTs were followed by EUS twice or more. The
      mean age was 66.4 +/- 8.3 years old and the mean period of follow-up was 23.8 +/-
      21.7 months. Fourteen (28%) of 50 GIMTs increased in size and the time taken for
      gastric GIMTs to double in size was 19.1 +/- 18.2 months. In multivariate
      logistic regression analysis, age (odds ratio [OR]=1.12, 95% confidence interval
      [CI]=1.03-1.21), non-upper area of the stomach (OR=5.08, 95%; CI=1.37-18.8) and
      the detection of an anechoic lesion on EUS (OR=5.90, 95%; CI=1.10-31.8) were the
      factors predicting an increase in size of gastric GIMTs. CONCLUSIONS: We
      evaluated gastric SMTs by EUS and clarified the factors predicting the growth of
      gastric GIMT. EUS is indispensable for the diagnosis and management of gastric
      SMTs.

PMID- 22633197
TI  - Etifoxine-induced acute hepatitis: a case series.
AB  - OBJECTIVE: Etifoxine is approved for the treatment of psychosomatic
      manifestations of anxiety. Several cases of acute hepatitis have been recently
      notified to the French pharmacovigilance centres. Our aim was to review all
      relevant cases of etifoxine hepatitis. METHODS: All cases of liver disorders
      involving etifoxine and reported since November 1995 were extracted from the
      French pharmacovigilance database. Only cases with suggestive chronological
      events, no other drug-related or non-drug causes, and sufficient information,
      were included. RESULTS: Of the 30 selected cases, 18 were retained for further
      analysis. The median duration of treatment before the onset of symptoms was 18
      days (11 to 61 days). The results of liver tests evidenced cytolytic hepatitis in
      15 cases and mixed-type hepatitis in 3. One patient also exposed to
      lisinopril/hydrochlorothiazide developed a fulminant hepatitis that required
      liver transplantation and six other patients had biological signs of severity.
      Except for the transplanted patient, 15 patients fully recovered within 3 months,
      and two clearly improved (further outcome unknown) after etifoxine withdrawal.
      CONCLUSION: One previously published case and our series confirm that etifoxine
      can cause acute liver injury with a possibly severe outcome. This adverse effect
      is not mentioned in the summary of the product characteristics.

PMID- 22633198
TI  - Specificities of sclerosing cholangitis in childhood.
AB  - Sclerosing cholangitis (SC) is a chronic cholestatic disease characterized by
      inflammation and obliterative fibrosis of the bile ducts, leading to biliary
      cirrhosis and ultimately to liver failure. Four main clinical forms can be
      distinguished in children: i) neonatal SC, most probably a genetic disease
      transmitted by autosomal recessive inheritance; ii) SC associated with strong
      features of autoimmunity (referred as autoimmune sclerosing cholangitis) with
      quite good response to immuno-suppression iii) primary SC of unknown etiology
      (i.e. without features of autoimmunity) and iv) SC secondary to various diseases,
      including Langerhans cell histiocytosis and immunodeficiencies. Ursodesoxycholic
      acid is considered the treatment of choice for all forms of SC but without proof
      of its effectiveness in preventing progression to secondary biliary cirrhosis. In
      patients with immunodeficiencies, early bone marrow transplantation is the only
      way to prevent secondary SC. Liver transplantation remains the only validated
      treatment in children with biliary cirrhosis. Recurrence of SC after liver
      transplantation has not been clearly demonstrated in children; however,
      recurrence of Langerhans cell histiocytosis with bile duct injury has been
      reported. For patients with severe immunodeficiency, a two-step liver then bone
      marrow transplantation protocol may be proposed.

PMID- 22633199
TI  - Liver transplantation for hepatocellular carcinoma: time for an international
      consensus.
AB  - Liver transplantation for hepatocellular carcinoma is widely accepted as the best
      treatment for this cancer. Since transplantation has become widely available (mid
      1980s), there has been no international consensus for this specific setting. This
      has now been done, and takes into account regional differences (cadaveric and
      living donor) and introduces expanded criteria, which vary according to the
      dynamics of the regional waiting list.

PMID- 22633200
TI  - [The value of hemoglobin A1c for diagnosis of diabetes mellitus and other changes
      in carbohydrate metabolism in women with recent gestational diabetes mellitus].
AB  - INTRODUCTION: Women with gestational diabetes mellitus (GDM) have an increased
      risk for developing diabetes mellitus (DM). Their postpartum metabolic
      classification using a 75g oral glucose tolerance test (75g OGTT) is recommended.
      The purpose of this study was to assess the value of hemoglobin A1c for
      postpartum evaluation in women with recent gestational diabetes mellitus.
      PATIENTS AND METHODS: Fifty-six women with recent GDM underwent a 75g OGTT at our
      center to assess postpartum changes in carbohydrate metabolism and were
      classified using diagnostic criteria of the American Diabetes Association (ADA).
      Receiver operating characteristic (ROC) curves analysis was used to assess the
      diagnostic performance of hemoglobin A1c, and kappa index was used to evaluate
      diagnostic agreement between hemoglobin A1c and 75g OGTT. RESULTS: DM was
      diagnosed in 7 women, and other categories of increased risk for DM in 25 women.
      Kappa index for diagnosis agreement was 0,22. Hemoglobin A1c >= 5.7% had 47%
      sensitivity and 71% specificity for identifying any change in carbohydrate
      metabolism. A hemoglobin A1c value >= 6.5 had 29% sensitivity and 100%
      specificity for diagnosis of DM. Area under the ROC curve was 0.57 for
      identifying any change in carbohydrate metabolism and 0.81 for diagnosis of DM.
      CONCLUSION: Using ADA cutoff values, hemoglobin A1c is not appropriate for
      postpartum glucose tolerance evaluation in women with recent gestational diabetes
      mellitus.

PMID- 22633201
TI  - Sensitive and rapid detection of ganciclovir resistance by PCR based MALDI-TOF
      analysis.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is associated with significant
      morbidity and mortality in transplant recipients. Resistance against ganciclovir
      is increasingly observed. According to current guidelines, direct drug resistance
      testing is not always performed due to high costs and work effort, even when
      resistance is suspected. OBJECTIVES: To develop a more sensitive, easy applicable
      and cost-effective assay as proof of concept for direct drug resistance testing
      in CMV surveillance of post-transplant patients. STUDY DESIGN: Five consecutive
      plasma samples from a heart transplant patient with a primary CMV infection were
      analyzed by quantitative real-time polymerase chain reaction (rtPCR) as a
      surrogate marker for therapy failure, and by direct drug resistance detection
      assays such as Sanger sequencing and the novel primer extension (PEX) reaction
      matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) based
      method. RESULTS: This report demonstrates that PEX reaction followed by MALDI-TOF
      analysis detects the A594V mutation, encoding ganciclovir resistance, ten days
      earlier compared to Sanger sequencing and more than 30 days prior to an increase
      in viral load. CONCLUSION: The greatly increased sensitivity and rapid turnaround
      time combined with easy handling and moderate costs indicate that this procedure
      could make a major contribution to improve transplantation outcomes.

PMID- 22633202
TI  - Thermal denaturation of a blue-copper laccase: formation of a compact denatured
      state with residual structure linked to pH changes in the region of histidine
      protonation.
AB  - The partial (absolute) heat capacity of a laccase enzyme from Myceliophthora
      thermophila (MtL) was determined from calorimetric scans in the 4.5-10.0 pH
      range. Above pH 7.5, the heat capacity of the thermally denatured state (C(p)(D))
      of this blue-copper glycoprotein is consistent with that for an unfolded, fully
      solvated polypeptide chain, if its carbohydrate content is taken into account.
      Below pH 7.5, C(p)(D) decreases and eventually levels off within the 5.5-4.5 pH
      region, where a compact, partially solvated denatured state is formed. In the
      compact state, denatured MtL is an oligomer, and exhibits considerable native
      like secondary structure and a perturbed environment of its copper atoms.
      Analysis of the pH dependence of C(p)(D) and the content of secondary structure
      gives results implying that His residues play an important role in the stability
      of the compact denatured state.

PMID- 22633204
TI  - Mortality in patients with ST-segment elevation myocardial infarction who do not
      undergo reperfusion.
AB  - Reperfusion therapy reduces mortality in patients presenting with ST-segment
      elevation myocardial infarctions (STEMI). However, some patients may not receive
      thrombolytic therapy or undergo primary percutaneous coronary intervention. The
      decision making and clinical outcomes of these patients have not been well
      described. In this study, 139 patients were identified from a total of 1,126
      patients with STEMI who did not undergo reperfusion therapy at a high-volume
      percutaneous coronary intervention center from October 2006 to March 2011.
      Clinical data, reasons for no reperfusion, management, and mortality were
      obtained by chart review. The mean age was 80 +/- 13 years (61% women, 31%
      diabetic, and 37% known coronary artery disease). Of the 139 patients, 72 (52%)
      presented with primary diagnoses other than STEMI, and 39 (28%) developed STEMI
      >24 hours after admission. The most common reasons for no reperfusion were
      advanced age, co-morbid conditions, acute or chronic kidney injury, delayed
      presentation, advance directives precluding reperfusion, patient preference, and
      dementia. Eighty-four patients (60%) had >= 3 reasons for no reperfusion. Factors
      associated with hospital mortality were cardiogenic shock, intubation, and
      advance directives prohibiting reperfusion after physician consultation. In
      hospital and 1-year mortality were 53% and 69%, respectively. In conclusion, at a
      high-volume percutaneous coronary intervention center, most patients presenting
      with STEMI underwent immediate catheterization. The decision for no reperfusion
      was multifactorial, with advanced age reported as the most common factor.
      Outcomes were poor in this population, and fewer than half of these patients
      survived to hospital discharge.

PMID- 22633203
TI  - Frequency of coronary artery disease in patients undergoing peripheral artery
      disease surgery.
AB  - The prevalence of coronary artery disease (CAD) in patients with peripheral
      arterial disease (PAD) varies widely in published reports. This is likely due at
      least in part to significant differences in how PAD and CAD were both defined and
      diagnosed. In this report, the investigators describe 78 patients with PAD who
      underwent preoperative coronary angiography before elective peripheral
      revascularization and provide a review of published case series. Among the
      patients included, the number with concomitant CAD varied from 55% in those with
      lower-extremity stenoses to as high as 80% in those with carotid artery disease.
      The number of coronary arteries narrowed by >= 50% was 1 in 28%, 2 in 24%, and 3
      in 19%; 28% did not have any angiographic evidence of CAD. The review of
      published research resulted in the identification of 19 case series in which a
      total of 3,969 patients underwent preoperative coronary angiography before
      elective PAD surgery; in the 2,687 who were described according to the location
      of the PAD, 55% had >= 1 epicardial coronary artery with >= 70% diameter
      narrowing. The highest prevalence of concomitant CAD was in patients with severe
      carotid artery disease (64%). In conclusion, despite sharing similar risk
      factors, the prevalence of obstructive CAD in patients with PAD ranges widely and
      appears to differ across PAD locations. Thus, the decision to perform coronary
      angiography should be based on indications independent of the planned PAD
      surgery.

PMID- 22633205
TI  - beta Blockers for prevention of exercise-induced left ventricular outflow tract
      obstruction in patients with hypertrophic cardiomyopathy.
AB  - Whether treatment with beta blockers (BBs) is of benefit to patients with
      hypertrophic cardiomyopathy (HC) and provocable outflow obstruction (with none or
      with only mild heart failure symptoms) is largely unresolved. Thus, we
      prospectively studied 27 patients with HC (age 36 +/- 15 years; 81% men) with New
      York Heart Association class I or II, without obstruction at rest, but with
      exercise-induced left ventricular outflow tract (LVOT) gradient of >= 30 mm Hg.
      Patients underwent exercise echocardiography at baseline and after treatment with
      nadolol (n = 18; 40 to 80 mg/day) or bisoprolol (n = 9; 5 to 10 mg/day),
      according to a prespecified protocol. Without the BBs, the postexercise LVOT
      gradient was 87 +/- 29 mm Hg and >50 mm Hg in 25 patients (93%). After a 12 +/- 4
      month period of BB treatment, the postexercise LVOT gradient had decreased to 36
      +/- 22 mm Hg (p <0.001) and was virtually abolished (to 0 or <30 mm Hg) in 14
      patients (52%), substantially blunted (>= 20 mm Hg reduction) in 9 (33%), and
      unchanged in only 4 (15%). Severe postexercise obstruction (range 58 to 80 mm Hg)
      persisted in 6 patients (22% compared to 93% without BBs; p <0.001).
      Nonresponders (residual postexercise gradient of >= 30 mm Hg with BBs) were
      characterized by an increased body mass index (hazard ratio 2.03/1 kg/m(2), 95%
      confidence interval 1.2 to 3.4; p <0.05). In conclusion, in patients with HC with
      mild or no symptoms, treatment with BBs can prevent the development of LVOT
      obstruction triggered by physiologic exercise. These findings provide a rationale
      for the novel strategy of early prophylactic pharmacologic treatment with
      standard, well-tolerated doses of BBs in physically active patients with
      provocable gradients, aimed at effective prevention of the hemodynamic burden
      associated with dynamic obstruction.

PMID- 22633206
TI  - Outcome and resource utilization of infants born with hypoplastic left heart
      syndrome in the Intermountain West.
AB  - The objective of the present study was to characterize the outcomes and resource
      utilization of all infants born with hypoplastic left heart syndrome (HLHS) in
      the Intermountain West. This was a retrospective cohort study of all infants born
      with HLHS in the Intermountain West from January 1995 and January 2010. The
      cohort was divided into 3 eras: era 1, 1995 to 1999; era 2, 2000 to 2004; and era
      3, 2005 to 2010. Cox proportional hazards regression analysis was performed to
      assess mortality. The lifetime hospitalization days and charges were also
      determined. Of the 245 infants identified, 65% were male infants and 172 (70%)
      underwent Stage 1 palliation. The transplant-free survival rate for the entire
      cohort was 33% at 14 years. The 1-year transplant-free survival rate for the
      surgical cohort was 60% in era 3. The infants whose initial presentation included
      shock, restrictive or intact atrial septum, chromosomal defects, or multiorgan
      dysfunction had an increased risk of death. A recent era of birth, greater
      birthweight, and older gestational age were associated with improved survival.
      The factors associated with mortality after stage 1 included surgical procedure
      type (Blalock-Taussig vs Sano shunt, hazard ratio 2.1), requirement for
      postoperative extracorporeal membrane oxygenation (hazard ratio 4.2),
      postoperative renal dysfunction (hazard ratio 3.0), anomalous pulmonary venous
      return (hazard ratio 2.9), and moderate or greater tricuspid valve regurgitation
      at any point (hazard ratio 2.0). For patients who had undergone stage 1, 2, or 3
      palliation, the median cumulative lifetime hospitalization was 32, 48, and 65
      days, and the median cumulative lifetime charges for hospitalization were
      $201,812, $253,183, and $296,213, respectively. In conclusion, although hospital
      based studies of HLHS have shown significantly improved survival after surgical
      palliation, population-based studies have shown that HLHS continues to have a
      high mortality and high resource utilization.

PMID- 22633207
TI  - Ultrastructural study of the male gamete of Glossobothrium sp. (Cestoda:
      Bothriocephalidea: Triaenophoridae) a parasite of Schedophilus velaini
      (Perciformes: Centrolophidae) in Senegal.
AB  - This paper describes the ultrastructure of the male gamete of Glossobothrium sp.
      (Bothriocephalidea: Triaenophoridae). The mature spermatozoon of Glossobothrium
      sp. is filiform and possesses two axonemes, a single helicoidal crested body, a
      parallel nucleus, parallel cortical microtubules and granules of glycogen. In
      Glossobothrium sp. we describe for first time a 200-250 nm thick crest-like body
      in the Bothriocephalidean. The anterior part of the spermatozoon exhibits a ring
      of 27 electron-dense cortical microtubules encircling the first axoneme. This
      structure persists until the appearance of the second axoneme. When the ring of
      electron-dense cortical microtubules disappears, the spermatozoon exhibits two
      bundles of thin cortical microtubules. The posterior part of the spermatozoon
      contains the posterior extremity of the second axoneme, the posterior extremity
      of the nucleus and few cortical microtubules. Soon nucleus disappears and the
      axoneme is disorganized. Thus the posterior extremity of the spermatozoon of
      Glossobothrium sp. exhibits only singlets produced by the disorganization of the
      doublets of the second axoneme and few cortical microtubules. This type of
      posterior extremity of the mature spermatozoon has never been described
      previously in the Triaenophoridae.

PMID- 22633208
TI  - [Use of Boussignac continuous positive airway pressure in a morbid obese patient
      subjected to thoracic surgery].

PMID- 22633210
TI  - Screening for anemia in patients on warfarin facilitates diagnosis of
      gastrointestinal malignancies and pre-malignant lesions.
AB  - INTRODUCTION: The prevalence and etiology of occult bleeding among patients on
      warfarin who are screened systematically for new anemia is largely unknown. We
      aimed to estimate the usefulness of following hemoglobin and mean red cell volume
      (MCV) with INR in order to screen for developing anemia as an indicator of occult
      bleeding. MATERIAL AND METHODS: All patients on warfarin controlled at our
      institution had measurements of complete blood count (CBC) with INR during 18
      months. Patients who fell>25 g/L and/or decrease of MCV over 5 fL or MCV<80 fL
      were contacted with instructions to undergo evaluation of anemia. RESULTS:
      Overall 3218 patients on warfarin were monitored at our institution and 442
      (13.7%) had anemia and 235 (7.3%) had unexplained anemia. A total of 163/235
      (69%) who were notified contacted their doctors and 82/163 (50%) were referred
      for investigation with upper and/or lower endoscopies. Gastrointestinal
      malignancies were found in 11 patients (10 colorectal cancers, 1 esophageal) and
      pre-cancerous lesions among 14 other patients. Additional 25/82 patients (30%)
      had upper and/or lower bleeding lesions such as ulcers and angiodysplasia. Based
      on 3669 years of observation, 73 patients needed to be screened for one year in
      order to identify one gastrointestinal lesion causing occult bleeding.
      CONCLUSIONS: Thirty percent of those endoscoped had malignant or pre-malignant
      diseases. Regular measurement of CBC concomitantly with INR in patients on
      warfarin therapy led to detection of otherwise asymptomatic diseases in a
      significant proportion of patients and might lead to earlier diagnosis of
      malignant and premalignant disease.

PMID- 22633209
TI  - [Management of direct action oral anticoagulants in the peri-operative period and
      invasive techniques].
AB  - The new direct-acting oral anticoagulants (ACOD) in patients on prolonged
      treatment require the need to balance the risk of haemorrhage by administering
      them against the risk of thrombosis on withdrawing them. Recommendations for
      their management are proposed in the present article: A) Thromboprophylaxis and
      general anaesthesia: the performing of regional anaesthesia if administered with
      an ACOD as thromboprophylaxis requires some safety intervals based on their
      pharmacokinetic parameters; B) Management of ACOD in elective surgery: in
      patients with normal renal function and a low haemorrhage/thrombosis risk, stop
      the ACOD two days before the surgery; it the haemorrhage/thrombosis risk is high
      and/or renal function is impaired, therapy with a low molecular weight heparin is
      proposed from 5 days prior to the surgery, and C) Management of ACOD in urgent
      surgery and associated haemorrhage: the systematic prophylactic administration of
      haemostatics is recommended. In the event of acute bleeding that may place the
      life of the patient at risk (due to volume or location), the administration of
      concentrated prothrombin complex, fresh plasma, or factor VIIa, must be assessed,
      together with general control measures of acute haemorrhage. These
      recommendations should be considered in the context of the use drugs that do have
      a specific antidote, where their monitoring by the usual coagulation tests is not
      routine, and with those in which there is limited experience. We believe they
      need to be reviewed in the future, depending on further studies and clinical
      experience obtained.

PMID- 22633211
TI  - Thromboembolic complications in membranous nephropathy patients with nephrotic
      syndrome-a prospective study.
AB  - BACKGROUND: Venous thromboembolism (VTE) is one of the most serious complications
      in membranous nephropathy (MN). We investigate the incidence of VTE in MN
      patients with nephrotic syndrome (NS). METHODS: A total of 100 MN patients with
      NS were enrolled into this prospective study. The diagnosis of VTE was based on
      contrast-enhanced dual source computed tomography angiography. RESULTS: Venous
      thromboembolism was demonstrated in 36 patients (36%). 33 patients (33%) had
      renal vein thrombosis (RVT), 17 patients (17%) had pulmonary embolism (PE). Flank
      pain was noted in 5 patients and gross hematuria in 2 patients with RVT. Dyspnea
      and chest pain were present in 9 patients with PE. The positive predictive value
      for D-dimer level was 69.4%, negative predictive value for D-dimer level was
      96.1% in patients with MN. Of all the risk factors presented, D-dimer level,
      proteinuria, the ratio of proteinuria to serum albumin were independent risk
      factors for the development of VTE (P<0.05), but the plasma level of antithrombin
      SH was not correlated with VTE in this study. In follow up, venous thrombosis
      disappeared after anticoagulant treatment with low-molecular-weight heparins in
      28 patients. CONCLUSION: Venous thromboembolism was confirmed in 36% of MN
      patients with NS. Renal vein thrombosis and pulmonary embolism are common and
      usually asymptomatic. Computed tomography angiography can be used effectively to
      examine suspected patients. Measurement of D-dimer is helpful in VTE diagnosis.
      It is important that clinicians are aware that VTE should be considered as a
      common complication in MN patients with NS.

PMID- 22633212
TI  - Soluble urokinase plasminogen activator receptor in patients with abdominal
      aortic aneurysm.
AB  - INTRODUCTION: In the present study we investigated the impact of soluble
      urokinase plasminogen activator receptor (suPAR) as a biomarker in patients with
      abdominal aortic aneurysm (AAA) in relation to conventional inflammatory markers,
      aneurysm size, and rupture. METHODS: suPAR and conventional inflammatory markers
      were measured in 119 patients with AAA and 36 controls without aneurysm matched
      by age, gender and smoking habit. RESULTS: The results support earlier studies
      suggesting a state of activated inflammatory response in patients with
      nonruptured AAA as expressed by elevated CRP and IL-6 compared with the controls.
      In contrast, suPAR showed similar levels in patients with nonruptured AAA
      compared with the controls. Unexpectedly, all follow-up patients (n=16) have
      significant (p<0.001) elevated suPAR levels three years postoperatively compared
      preoperatively. CONCLUSIONS: suPAR does not seem to be a useful biomarker in the
      AAA disease. The role of the postoperative elevation of suPAR needs to be further
      elucidated.

PMID- 22633213
TI  - [Orbital inflammatory pseudotumor with optic neuritis in Behcet's disease].
AB  - OBJECTIVE: To report an atypical case of orbital inflammatory pseudotumor
      associated with optic neuritis revealing Behcet's disease. CASE REPORT: A 37-year
      old man was worked up for headache and progressive decreased bilateral visual
      acuity most profound in the left eye. Initial ophthalmologic exam was without
      abnormal findings. Orbital CT scan and MRI appeared consistent with orbital
      inflammatory pseudotumor involving the left lateral rectus muscle (orbital
      myositis). The patient was treated with oral corticosteroids, but clinical
      response was incomplete. Follow-up ophthalmologic exam revealed acute
      inflammatory right optic neuritis (visual acuity: 5/10, papillitis on fundus exam
      and papillary edema on fluorescein angiography) and persistence of left orbital
      myositis. The diagnosis of Behcet's disease with ocular complications was made on
      the basis of recurrent oral ulcers, scars from genital ulcerations and
      pseudofolliculitis. It was decided to treat the patient with a bolus of IV
      methylprednisolone for 3 consecutive days, followed by oral prednisolone and
      cochicine, leading to stabilization of the ocular manifestations. CONCLUSION: To
      our knowledge, this is the first report of such an association leading to a
      diagnosis of Behcet's disease. The coexistence of these two manifestations as
      well as the contralateral nature of the involvement speaks to the pathogenic
      mechanism of these complications (systemic vasculitis).

PMID- 22633214
TI  - Uveal metastasis revealing lung cancer.
AB  - BACKGROUND: Uveal metastases (UM) are the most common intraocular malignancies
      and can be the first manifestation of a disseminated disease. The purpose of this
      study is to determine the frequency with which uveal metastasis results in a
      diagnosis of lung cancer, to describe the clinical characteristics of patients
      with lung cancer metastatic to the uvea, as well as diagnostic difficulties that
      may be encountered. PATIENTS AND METHODS: We carried out a single-center
      retrospective study of the medical records of all patients who presented with a
      UM between 1999 and 2010 at the institut Curie in Paris. From these patients, we
      retrospectively studied UM secondary to lung cancer. A work-up including thoracic
      abdominal-pelvic CT was performed for each patient in whom the primary source of
      choroidal metastasis was unknown. RESULTS: Of 109 patients presenting with UM, 43
      were diagnosed with primary lung cancer (39.4%). Of those 43 patients, the UM was
      observed prior to the lung cancer in 31 patients (72.1%). Demographic data
      included 61% male and 39% female, mean age 59.1 years (range: 31-78), and mean
      life expectancy after diagnosis of UM was 7.5 months (range: 0.7-29). Other
      metastatic sites were associated with UM in 90.7% of the patients. In all, 90.7%
      of the patients presented with blurred vision, and 25.6% with pain or
      inflammation. UM were located within the choroid for 39 patients (90.7%), the
      iris for three patients (7.3%) and the vitreous for one patient. Seventy percent
      of patients had a solitary lesion, 76.7% had unilateral involvement, and 23.3% of
      cases were bilateral. Mean thickness on B-scan ultrasonography was 3.61 mm
      (range: 1-8.5 mm). In all, 81.4% of UM were unpigmented, while 18.6% showed
      pigment mottling. In all, 20.9% of patients were referred with the diagnosis of
      choroidal melanoma from their regular ophthalmologist, and three of the 43
      patients (6.9%) were initially misdiagnosed and treated for melanoma at Curie.
      Chest X-ray was unremarkable in 18.9% of patients. CONCLUSION: UM is often the
      first manifestation of disseminated disease and requires a search for the primary
      tumor, in particular lung cancer. Standard chest X-ray cannot rule out the
      diagnosis. Metastases may be solitary with heterogenous pigmentation, and the
      differential diagnosis from uveal melanoma may be difficult, requiring the
      expertise of a referral center.

PMID- 22633215
TI  - [Efficacy and tolerability of highly crosslinked hyaluronic acid injections in
      the management of the enophthalmous orbit].
AB  - OBJECTIVE: Evaluation of the efficacy and tolerability of highly crosslinked
      hyaluronic acid injections in treating the enophthalmous orbit. METHODS:
      Retrospective study of 11 enophthalmic patients who received an intraorbital
      injection of Juvederm((r)) Voluma between June 2007 and October 2008. The mean
      follow-up was 19 months (range 12-25 months). RESULTS: Twelve orbits of 11
      patients were treated, including nine with post-enucleation socket syndrome
      (PESS). Volume loss was corrected in 66.67% of cases (eight orbits) with only one
      intraorbital injection. Two patients requested an additional injection, achieving
      a final success rate of 83.33%. A rate of 16.67% (two orbits) developed some
      bruising, mild swelling and hypersensivity at the injection site within 24 hours
      of administration of the filler, representing minor, temporary side-effects of
      which the patients had been forewarned. Persistent edema was noted in 16.67% of
      cases, likely due to an overcorrection of ptosis, and ptosis was exacerbated in
      16.67% of cases (two orbits). One ptosis was corrected after several months, with
      no particular difficulties related to the hyaluronic acid. No additional
      complications were identified. CONCLUSION: Juvederm((r)) Voluma appears to be an
      effective filler for reduction of enophthalmos with a single intraorbital
      injection. In our experience, this product seems to have a longer duration of
      action than reported by the manufacturer and appears to perform like a semi
      permanent or even permanent filler.

PMID- 22633216
TI  - [Cosmetic blepharoplasty complicated by necrotizing periorbital fasciitis: a case
      report].
AB  - Necrotizing periorbital or palpebro-orbital fasciitis represents a unique
      anatomical site for necrotizing fasciitis, which is an extremely rare and very
      severe, potentially devastating bacterial infection, rapidly leading to facial
      necrosis with loss of vision and even death of the patient from toxic shock. In
      this paper, we report a case of necrotizing periorbital fasciitis as a
      complication of cosmetic lower eyelid blepharoplasty. Necrotizing fasciitis most
      often affects the upper and lower limbs, the trunk and the perineal area. It is
      rarely observed in the facial region due to the rich blood supply in this area.
      The most commonly implicated pathogen is group A, beta-hemolytic
      "pyogenic"Streptococcus, either alone or in combination with other bacteria, such
      as staphylococcus or pseudomonas. Mortality varies according to the series and
      anatomical site. The mortality rate for necrotizing fasciitis is approximately 28
      %. It is slightly lower in the periorbital area (15 %). Risk factors for death
      include alcoholism, diabetes mellitus, immunocompromise, hematologic or pulmonary
      diseases, and the identity of the causative agent (group A Streptococcus),
      although approximately 50 % of patients have no predisposing conditions.
      Management of periorbital necrotizing fasciitis is based on early detection of
      initial symptoms and on aggressive multidisciplinary treatment including surgical
      debridement of necrotic areas and antibiotic coverage. The timeliness of
      treatment and the multidisciplinary approach are considered to be the two
      essential factors in influencing the mortality and morbidity of this condition.

PMID- 22633217
TI  - (68)Ga-BPAMD: PET-imaging of bone metastases with a generator based positron
      emitter.
AB  - PURPOSE: Bone metastases are a serious aggravation for patients suffering from
      cancer. Therefore, early recognition of bone metastases is of great interest for
      further treatment of patients. Bisphosphonates are widely used for scintigraphy
      of bone lesions with (99m)Tc. Using the (68)Ge/(68)Ga generator together with a
      macroyclic bisphosphonate a comparable PET-tracer comes into focus. PROCEDURES:
      The bisphosphonate DOTA-conjugated ligand BPAMD was labelled with (68)Ga.
      [(68)Ga]BPAMD was evaluated in vitro concerning binding to hydroxyapatite and
      stability. The tracer's in vivo accumulation was determined on healthy rats and
      bone metastases bearing animals by MU-PET. RESULTS: BPAMD was labelled
      efficiently with (68)Ga after 10 min at 100 degrees C. [(68)Ga]BPAMD showed high
      in vitro stability within 3h and high binding to hydroxyapatite. Consequently, MU
      PET experiments revealed high accumulation of [(68)Ga]BPAMD in regions of
      pronounced remodelling activity like bone metastases. CONCLUSIONS: (68)Ga BPAMD
      reveals great potential for diagnosis of bone metastases via PET/CT. The straight
      forward (68)Ga-labelling could be transferred to a kit-preparation of a cyclotron
      independent PET tracer instantaneously available in many clinical sites using the
      (68)Ge/(68)Ga generator.

PMID- 22633218
TI  - Radiolabeling of [18F]altanserin - a microfluidic approach.
AB  - INTRODUCTION: Our aim was the optimization of radiochemical parameters for the
      microfluidic preparation of [(18)F]altanserin. The four main parameters evaluated
      were (1) precursor concentration, (2) reaction temperature, (3) bolus flow rate
      through the microreactor and (4) bolus volume. METHODS: For the determination of
      optimal reaction conditions within a flow-through microreactor synthesizer, 5-400
      MUL of precursor and dried [(18)F]fluoride solution were simultaneously pushed
      through the temperature-controlled reactor (180-220 degrees C) with defined bolus
      flow rates of 10-60 MUL/min. Radiochemical incorporation yields (RCIYs) were
      examined using a thin layer chromatography (TLC) set-up and radio- high
      performance liquid chromatography (HPLC). RESULTS: Optimum reaction parameters
      for the microfluidic set-up were determined as following: 220 degrees C, 5-10
      MUL/min pump rate per reactant (10-20 MUL/min reaction overall flow rate) and
      2mg/mL precursor concentration in the reaction mixture. Applying these optimized
      conditions, RCIYs of 53.7 +/- 7.9 were observed for scaled-up preparations. A
      positive "bolus effect" was observed: applying higher reaction volume resulted in
      increased RCIYs. CONCLUSION: This study proved that the reaction bolus volume is
      an essential parameter influencing the RCIY of [(18)F]altanserin. A possible
      explanation is the inhomogeneous distribution within the reaction volume probably
      caused by diffusion at the bolus interface. This important finding should be
      considered an important variable for the evaluation of all novel radiotracers
      labeled using a flow-through reactor device.

PMID- 22633221
TI  - Exsanguinating hemorrhage following third molar extraction: report of a case and
      discussion of materials and methods in selective embolization.

PMID- 22633219
TI  - Dose-escalation study of thoracic radiotherapy in combination with pemetrexed
      plus Cisplatin followed by pemetrexed consolidation therapy in Japanese patients
      with locally advanced nonsquamous non-small-cell lung cancer.
AB  - BACKGROUND: Pemetrexed has radiosensitizing potential when evaluated in vitro in
      combination with platinum-containing compounds and radiation. We determined the
      recommended dose (RD) of thoracic radiotherapy (TRT) with a concurrent
      chemotherapy combination of pemetrexed and cisplatin in Japanese patients with
      nonsquamous non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible
      patients were histologically confirmed as having locally advanced nonsquamous
      NSCLC. Study treatment consisted of 2 phases: concurrent chemoradiation and
      consolidation. In the concurrent chemoradiation phase, all patients received
      pemetrexed 500 mg/m(2) plus cisplatin 75 mg/m(2) on day 1 of a 21-day interval
      for 3 cycles. The first 6 patients were given 60 Gy concurrently at level 1 dose
      (L1D). If dose-limiting toxicity (DLT) occurred in < 2 patients at L1D, radiation
      was escalated to 66 Gy (level 2 dose [L2D]). RESULTS: Eighteen patients were
      treated and completed chemoradiotherapy; 12 completed the consolidation phase. In
      the concurrent chemoradiation phase, 1 patient experienced 2 DLTs [grade 3
      anorexia and diarrhea] at L1D. Because no DLT was observed at L2D, it was
      determined to be the RD. Common toxicities >=grade 3 were neutropenia and
      leukopenia. At L1D, 1 patient each experienced grade 2 and grade 3 pneumonitis,
      and 2 patients experienced grade 2 esophagitis. Six patients experienced grade 2
      pneumonitis and 3 patients experienced grade 2 esophagitis at L2D. Fifteen
      patients achieved partial response (PR), 2 had stable disease (SD), and 1 had
      progressive disease (PD). CONCLUSION: Expected toxicities from concurrent
      chemoradiation were not worsened with concurrent TRT at a total dose of 66 Gy
      combined with pemetrexed in Japanese patients with locally advanced (LA)
      nonsquamous NSCLC.

PMID- 22633220
TI  - Carboplatin and paclitaxel plus ASA404 as first-line chemotherapy for extensive
      stage small-cell lung cancer: a multicenter single arm phase II trial (SAKK
      15/08).
AB  - INTRODUCTION: Small-cell lung cancer (SCLC) is a highly vascularized tumor.
      ASA404 is a tumor vascular disrupting agent. This is the first trial to report
      the effects of combining chemotherapy with ASA404 in SCLC. METHODS: Patients with
      untreated metastatic SCLC were treated with carboplatin (area under curve, 6)
      plus paclitaxel (175 mg/m(2)) plus ASA404 (1800 mg/m(2)) on day 1 every 21 days
      for up to 6 cycles. The primary endpoint was the progression-free survival (PFS)
      rate at 24 weeks. RESULTS: Median age was 61 years; 53% were women, 41% had
      weight loss; and 96% had a performance status of 0-1. Twelve patients completed
      all 6 cycles, and most adverse events were related to chemotherapy. Median PFS
      and time to progression were 7.0 months (95% CI, 5.7-9.4 months) and 7.5 months
      (95% CI, 5.7-9.4 months), respectively. The progression-free survival (PFS) rate
      at 24 weeks was 41% (95% CI, 18%-65%). The overall response rate was 94%. The
      median overall survival time was 14.2 months (95% CI, 8.2-16.0 months) and 1-year
      survival was 57%. The median follow-up time was 17.7 months. Due to negative
      results with ASA404 in non-small-cell lung cancer trials, the trial was stopped
      prematurely after 17 of 56 planned patients were being accrued. CONCLUSIONS: This
      is the first report of a clinical trial with a vascular disrupting agent in SCLC.
      No unexpected toxicity was observed. PFS was not prolonged with carboplatin and
      paclitaxel plus ASA404.

PMID- 22633222
TI  - Proteomic analysis of plasma from Holstein cows testing positive for
      Mycobacterium avium subsp. paratuberculosis (MAP).
AB  - Johne's disease (JD) is a widespread and economically important chronic
      inflammatory disease of the small intestine of ruminants caused by Mycobacterium
      avium subsp. paratuberculosis (MAP). Although there are several techniques
      available for diagnosis of JD, their sensitivity is questionable. New proteome
      profiling methods, such as serum/plasma protein fingerprinting by 2-Dimensional
      Fluorescence Difference Gel Electrophoresis (2D-DIGE), may therefore be useful
      for identifying novel protein biomarkers of MAP infection. In this study, plasma
      samples were collected from 380 Holstein cows and screened for the presence of
      MAP infection using the M.pt. Johne's antibody Kit (IDEXX). Five negative (MAP-),
      and 5 strongly positive (MAP+) cows were selected for proteomic analysis. Highly
      abundant proteins were depleted from the plasma samples using the ProteoMiner
      technology (Bio-Rad) to enhance the resolution of low abundance proteins. Plasma
      samples from MAP-, MAP+, and a pooled internal control were labelled with
      different fluorescent dyes and separated based on their isoelectrical point (IP)
      and then their molecular weight. Gel images of the fluorescent plasma protein
      maps were acquired using a Typhoon scanner and analyzed using the DeCyder
      software. Proteins that were differentially expressed were excised from the gels,
      trypsin digested, and subjected to MS/MS analysis for identification. Six
      proteins were identified as being up-regulated at least 2-fold in MAP+ cows
      including: transferrin, gelsolin isoforms alpha & beta (actin binding protein -
      ABP), complement subcomponent C1r, complement component C3, amine oxidase -
      copper containing 3 (AOC3), and coagulation factor II (thrombin) (p<0.05). Two
      proteins that were down-regulated approximately 2-fold in the MAP+ cows included
      coagulation factor XIII -B polypeptide (COAFXIII), and fibrinogen gamma chain
      (FGG) and its precursor.

PMID- 22633223
TI  - Factors associated with arthroscopically determined scaphoid fracture
      displacement and instability.
AB  - PURPOSE: To identify factors associated with arthroscopically diagnosed scaphoid
      fracture displacement and instability. METHODS: This was a secondary use of data
      from 2 prospective cohort studies. The studies included 58 consecutive adult
      patients with a scaphoid fracture who elected arthroscopy-assisted operative
      fracture treatment: some for displacement, some as part of a prospective
      protocol, and others to avoid a cast. All patients had preoperative computed
      tomography with reconstructions in planes defined by the long axis of the
      scaphoid. RESULTS: Arthroscopy revealed 38 unstable fractures (movement between
      fracture fragments; 66%), 27 of which were also displaced. All arthroscopically
      determined displaced fractures were unstable, and 11 of the 31 arthroscopically
      determined, nondisplaced fractures were unstable. There was a significant
      correlation between radiographic comminution (more than 2 fracture fragments) and
      arthroscopically determined displacement and instability. CONCLUSIONS:
      Radiographic comminution is associated with displacement and instability as
      determined by arthroscopy.

PMID- 22633224
TI  - The effects of edema and self-adherent wrap on the work of flexion in a cadaveric
      hand.
AB  - PURPOSE: Early motion protocols after flexor tendon repair often require hand
      therapy in edematous digits. Self-adherent wraps are used in the postoperative
      period to reduce edema. The purpose of this study was to determine whether the
      presence of a self-adherent wrap affected the work of flexion during early motion
      protocols. METHODS: In an unpreserved cadaveric hand, the flexor digitorum
      profundus and flexor pollicis longus tendons were identified and attached to a
      tensile testing machine to measure work of flexion (WoF). We simulated
      subcutaneous edema by injecting normal saline into the digits. Moderate and
      severe edema was simulated by 10% and 20% increases in circumference of the
      digits, respectively. We evaluated 2 commonly used products: 2.5-cm Coban self
      adherent wrap (3M, St. Paul, MN) and 2.5-cm Co-Wrap cohesive bandage (Hartmann,
      Rock Hill, SC). Statistical analyses include analysis of variance, 95% confidence
      intervals for average responses, and graphical display of both data and model
      predictions. RESULTS: In digits without edema or wraps, WoF ranged from 0.0114 J
      (small finger) to 0.0710 J (thumb). Without wraps, simulated moderate and severe
      edema was predicted to increase WoF by an average of 23% and 71%, respectively.
      Application of self-adherent wrap increased WoF values significantly in all
      digits. In the majority of conditions tested, application of self-adherent wrap
      increased WoF more significantly than moderate edema did. The effects of edema
      and self-adherent wrap were additive, producing WoF values 4 times the baseline
      values. CONCLUSIONS: Edema and self-adherent wrap increased WoF in this model.
      Therapists and surgeons should be aware of increased stress placed on tendons
      when early motion protocols are initiated in the presence of edema and self
      adherent wrap. CLINICAL RELEVANCE: We recommend removal of self-adherent wrap
      before starting a therapy session.

PMID- 22633225
TI  - Functional outcomes after nonsurgical treatment of distal radius fractures.

PMID- 22633226
TI  - Steroid injection and needle aponeurotomy for Dupuytren contracture: a
      randomized, controlled study.
AB  - PURPOSE: To compare flexion deformity at 6 months in patients with Dupuytren
      contracture who had percutaneous needle aponeurotomy (PNA) combined with a series
      of triamcinolone acetonide (TA) injections to that of patients who had PNA alone.
      METHODS: Forty-seven patients with Dupuytren disease who were candidates for PNA
      (at least 1 contracture of at least 20 degrees ) participated in the study.
      Patients were randomized either to receive TA injections immediately following
      and 6 weeks and 3 months after the procedure or to receive no injections.
      Injections were administered into cords. The number of injections and the amount
      of TA per injection was determined based on the number of digits involved and the
      cord size. All subjects returned for 3 follow-up visits after the procedure, and
      contractures were measured using a goniometer. Change in total active extension
      deficit (TAED) was analyzed using a repeated measures analysis of variance to
      assess for differences between groups, time points, and interaction between group
      and time point. Descriptive statistics were calculated for all variables of
      interest. Continuous measures were summarized using means and standard
      deviations. RESULTS: There was no significant difference in TAED between groups
      before cord aponeurotomy. Correction at 6 months was 87% of preoperative TAED for
      the TA group versus 64% for the control group. This difference was statistically
      significant. The amount of TA administered did not correlate with TAED
      improvement. CONCLUSIONS: The study group who received TA in combination with PNA
      experienced a significantly greater degree of correction of flexion deformity at
      6 months than those who had PNA alone.

PMID- 22633227
TI  - Preoperative magnetic resonance imaging for evaluating scaphoid nonunion.

PMID- 22633228
TI  - Diagnostic considerations for monoarticular arthritis of the hand and wrist.

PMID- 22633229
TI  - Optimal fixation of oblique scaphoid fractures: a cadaver model.
AB  - PURPOSE: Acute scaphoid fractures are commonly fixed with headless cannulated
      screws positioned in the center of the proximal fragment. Central placement of
      the screw may be difficult and may violate the scaphotrapezial joint. We
      hypothesize that placement of the screw through the scaphoid tuberosity will
      achieve perpendicular fixation of an oblique waist fracture and result in more
      stable fixation than a screw in the center of the proximal fragment. METHODS: We
      designed oblique osteotomies for 8 matched pairs of cadaver scaphoids and fixed
      each specimen with a headless cannulated screw. In 1 specimen, we positioned the
      screw at the center of the proximal fragment; we placed its matched pair
      perpendicular to the fracture. The perpendicular screw was directed through the
      scaphoid tuberosity. We placed the specimen under the increasing load of a
      pneumatically driven plunger. We compared stiffness, load, distance at failure,
      and mechanism of failure between the central and perpendicular screw groups.
      RESULTS: We found no difference between groups. Stiffness was identical in both
      groups (131 N/mm) and load to failure was similar (central screw, 137 N vs
      perpendicular screw, 148 N). CONCLUSIONS: In this biomechanical model of an
      unstable scaphoid fracture, we found that similar stability of fixation had been
      achieved with a screw perpendicular to the fracture plane with entry through the
      tuberosity, compared with a screw in a central position in the proximal fragment.
      This study suggests that placing the screw through the tuberosity, perpendicular
      to a short oblique fracture, will not impair fixation stability. CLINICAL
      RELEVANCE: Percutaneous fixation of scaphoid fractures has become popular
      although it is technically challenging. An easier distal approach through the
      tuberosity, without violating the scaphotrapezial joint, may not impair the
      fixation stability of an oblique fracture.

PMID- 22633230
TI  - Supplemental graft fixation for distal radius vascularized bone graft.
AB  - Vascularized bone grafts from the distal radius have been used successfully for
      the treatment of scaphoid nonunions. Typically, the harvested graft is secured
      into the scaphoid with a press-fit technique. This type of fixation may lead to
      graft extrusion in the early postoperative period, and thus to treatment failure.
      In this technical note, we describe the use of micro bone suture anchors for
      supplemental fixation of the vascularized bone graft into the scaphoid. It is a
      simple and quick technique and provides an enhanced fixation of the vascularized
      bone graft, which is beneficial during the early critical period of bone healing.

PMID- 22633231
TI  - Sonography-guided arthroscopy for wrist ganglion.
AB  - PURPOSE: To describe how to combine the complementary features of sonography and
      arthroscopy to make the arthroscopic resection of wrist ganglions a safer and
      more reliable surgery. METHODS: A total of 22 patients with wrist ganglions had
      sonography-assisted arthroscopic resection. Sonographic visualization of
      ganglions, adjacent structures (ie, vessels, nerves, and tendons), and the
      cycling tip of the arthroscopic shaver was assessed. Arthroscopic visualization
      of the ganglions or ganglion stalk was also assessed. Clinical outcome measures
      included wrist range of motion, grip strength, and our patient-rated Hand 20
      questionnaire. RESULTS: Sonographic visualization of the ganglion stalk, adjacent
      structures, and the cycling tip of the arthroscopic shaver was possible in all 22
      cases. However, ganglion stalks were visualized by arthroscopy in only 4 cases.
      The mean range of motion and grip strength were not significantly changed
      following surgery. However, the mean Hand 20 score was significantly improved
      from 17 to 6 at final follow-up. Ganglion recurrence was seen in 2 cases at 6 and
      8 months after surgery. CONCLUSIONS: Sonography-guided wrist arthroscopy provides
      several advantages for surgeons, including visualization of the ganglions and
      ganglion stalk, as well as of the arthroscopic shaver and adjacent structures
      such as nerves, vessels, and tendons to perform surgery safely.

PMID- 22633232
TI  - Lunotriquetral ligament tears.

PMID- 22633242
TI  - Gas chromatography-mass spectrometry based metabolic profiling for the
      identification of discrimination markers of Angelicae Radix and its application
      to gas chromatography-flame ionization detector system.
AB  - Gas chromatography (GC)-based metabolomics technologies were applied for quality
      control of Angelicae Radix, an herbal medicine commonly used in Japan and China.
      Since Angelica roots are priced and graded differently based on their species and
      cultivation area, there is a need for a simple and reproducible method to
      discriminate Angelica roots. Here, we used GC-MS profiling data to construct a
      discrimination method for species and cultivation area of A. Radix. Seventy-six
      primary metabolites were identified. The quality factors of A. Radix were
      successfully classified using metabolic profiling and the orthogonal projections
      to latent structures-discriminant analysis (OPLS-DA) technique. Sorbitol and a
      glucose/4-aminobutyric acid combination were chosen as bio-markers from S-plot of
      OPLS-DA. Application of these selected bio-markers to a more practical and cost
      efficient system, namely gas chromatography-flame ionization detector (GC-FID)
      system were also assessed. As a result, the same separations of sorbitol, glucose
      and 4-aminobutyric acid in box plots were obtained from GC-FID data. Our results
      demonstrate that GC-based metabolic markers can be readily applied for the
      establishment of a practical quality control method for A. Radix.

PMID- 22633233
TI  - Elongation of the dorsal carpal ligaments: a computational study of in vivo
      carpal kinematics.
AB  - PURPOSE: The dorsal radiocarpal (DRC) and dorsal intercarpal (DIC) ligaments play
      an important role in scapholunate and lunotriquetral stability. The purpose of
      this study was to compute changes in ligament elongation as a function of wrist
      position for the DRC and the scaphoid and trapezoidal insertions of the DIC.
      METHODS: We developed a computational model that incorporated a digital dataset
      of ligament origin and insertions, bone surface models, and in vivo 3-dimensional
      kinematics (n = 28 wrists), as well as an algorithm for computing ligament fiber
      path. RESULTS: The differences between the maximum length and minimum length of
      the DRC, DIC scaphoid component, and DIC trapezoidal component over the entire
      range of motion were 5.1 +/- 1.5 mm, 2.7 +/- 1.5 mm, and 5.9 +/- 2.5 mm,
      respectively. The DRC elongated as the wrist moved from ulnar extension to radial
      flexion, and the DIC elongated as the wrist moved from radial deviation to ulnar
      deviation. CONCLUSIONS: The DRC and DIC lengthened in opposing directions during
      wrist ulnar and radial deviation. Despite complex carpal bone anatomy and
      kinematics, computed fiber elongations were found to vary linearly with wrist
      position. Errors between computed values and model predictions were less than 2.0
      mm across all subjects and positions. CLINICAL RELEVANCE: The relationships
      between ligament elongation and wrist position should further our understanding
      of ligament function, provide insight into the potential effects of dorsal wrist
      incisions on specific wrist ranges of motion, and serve as a basis for modeling
      of the wrist.

PMID- 22633244
TI  - Controversies in family planning: retained products of conception.

PMID- 22633243
TI  - Moloney murine leukemia virus genomic RNA packaged in the absence of a full
      complement of wild type nucleocapsid protein.
AB  - The current model for MLV genomic RNA (gRNA) packaging predicts that of the
      thousands of Gag proteins in a budding virion, only a small number (<=1%) may be
      necessary to recruit gRNA. Here, we examined the threshold limits of functional
      Gag required to package gRNA using wild-type (WT) and packaging deficient mutant
      nucleocapsid (NC) phenotypically mixed virions. Although gRNA packaging was
      severely diminished for the NC mutant, the residual encapsidated RNA dimer
      displayed motility on gels, thermostability, and integrity that was
      indistinguishable from that of WT. In phenotypically mixed virions, gRNA
      encapsidation recovered to within approximately two-fold of WT levels when the
      amount of WT NC was 5-10% of the total. Our results demonstrate that NC's roles
      in gRNA dimerization and packaging are genetically separable. Additionally, MLV
      gRNA packaging does not require 100% WT NC, but the amount of functional NC
      required is greater than the predicted minimum.

PMID- 22633245
TI  - Long-acting reversible contraception method use among Title X providers and non
      Title X providers in California.
AB  - BACKGROUND: Publicly funded family planning services play an important role in
      reducing unintended pregnancy by providing access to effective contraception. We
      assessed whether California family planning providers receiving federal Title X
      funds are more likely to offer on-site long-acting reversible contraception
      (LARC) methods than those who do not receive these funds. STUDY DESIGN: Using
      2009 administrative data, we examined on-site utilization of LARC by clinic type
      (Title X public, non-Title X public, or private) and constructed beta-binomial
      logistic regression models. RESULTS: The odds of on-site LARC services in non
      Title X public and private providers were decreased by 35% [Odds Ratio (OR)=0.65,
      95% confidence interval (CI) 0.54-0.79] and 61% [OR=0.39, 95% CI 0.32-0.47],
      respectively, compared to those of Title X providers after controlling for clinic
      size, urban/rural location, and proportion of teen, African-American, and Latina
      clients. CONCLUSIONS: On-site utilization of LARC is a potential quality
      indicator for family planning programs. Title X resources are associated with
      increased use of LARC.

PMID- 22633246
TI  - Interest of simultaneous Chlamydia trachomatis and Neisseria gonorrhoeae
      screening at the time of preabortion consultation.
AB  - BACKGROUND: This study was conducted to estimate the prevalence and risk factors
      of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection among
      women consulting for abortion and to discuss screening for these pathogens in
      this population. STUDY DESIGN: Systematic CT/NG screening using real-time
      polymerase chain reaction was performed on cervical samples from 421 women who
      consulted for abortion over a 6-month period. RESULTS: Among the 421 women
      included, 13 had symptoms of gynecological infection, and 408 were asymptomatic.
      Only one of the symptomatic women was infected with CT (7.7%), and none of the
      women were infected with NG. Among the asymptomatic women, 40 were CT infected
      (9.8%), and three were NG infected. The overall prevalence was 9.7% for CT
      infection and 0.7% for NG infection. CONCLUSIONS: This population had a high
      prevalence of CT infection and a low prevalence of NG infection. Most infections
      were asymptomatic, which could justify systematic simultaneous screening for
      these two pathogens.

PMID- 22633247
TI  - Preventing unintended pregnancy among young women in Kenya: prospective cohort
      study to offer contraceptive implants.
AB  - BACKGROUND: Subdermal contraceptive implants have low discontinuation rates but
      are underused among young women in Africa. This study aimed to isolate the role
      initial contraceptive method has on preventing unintended pregnancy. STUDY
      DESIGN: We recruited 399 Kenyan women aged 18-24 years into a prospective cohort
      study if they wanted short-acting hormonal methods (injectable or oral
      contraceptives). We offered an implant and formed two study groups: implant and
      short-acting. For contraceptive discontinuation/pregnancy, we used log-rank tests
      and proportional hazards models. We applied intent-to-treat principles to
      evaluate the role of initial method choice on future pregnancy. RESULTS: Twenty
      four percent opted for an implant (n=97), and the remainder opted for a short
      acting method (n=299). The 18-month discontinuation probability was 21 per 100
      for implant users and 43 per 100 for the short-acting method group (p=.001).
      Twenty-two unintended pregnancies occurred; all were among the short-acting
      group. The adjusted relative risk of pregnancy among the short-acting group vs.
      implant group was 7.4 (95% confidence interval: 1.6-34.5). CONCLUSIONS: Many
      young Kenyan women found implants to be a reasonable alternative to short-acting
      methods. Having choice is essential, and starting on implants provides
      substantial and clear protection from unintended pregnancy relative to short
      acting methods.

PMID- 22633248
TI  - Suspect online sellers and contraceptive access.
AB  - BACKGROUND: Issues surrounding contraception access have been a national focus.
      During this debate, adolescent and adult women may seek these products online.
      Due to safety concerns, including potential counterfeit forms, we wished to
      assess whether online "no prescription" contraceptives were available. STUDY
      DESIGN: We assessed online availability of reversible, prescription contraceptive
      methods resulting in <10 undesired pregnancies/year, i.e., Depo-Provera shot;
      oral contraceptives; NuvaRing; Ortho Evra patch; Paragard and Mirena IUDs; and
      Implanon/Nexplanon implants. Using Google search "buy ITEM no prescription," we
      reviewed the first five result pages for "no prescription" vendors. Searches were
      conducted 1/3/2012-2/20/2012. RESULTS: All contraceptives were available as "no
      prescription" products. Furthermore, IUDs were advertised as "over-the-counter"
      and YouTube videos provided "how to" videos, including a cartoon version. We also
      found that illicit online pharmacy marketing is shifting from direct search
      engine access to social media (Facebook, Twitter, Slidehare, flickr). CONCLUSION:
      Online contraceptive sales represent patient safety risks and a parallel system
      of high-risk product access absent professional guidance. Providers should
      educate patients, while policy makers employ legal strategies to address these
      systemic risks.

PMID- 22633249
TI  - [Does intellectual activity prevent cognitive impairment? Relationships between
      cognitive reserve and mild cognitive impairment].
AB  - An in-depth review is presented of the role that cognitive reserve plays in the
      emergence of (mild cognitive impairment (MCI), and its progression to dementia by
      using different indicators. The studies reviewed provide support to the
      hypothesis that the reserve influences the manifestation of symptoms of cognitive
      impairment and at least partially, in its progression to dementia. The role of
      indicators of reserve are discussed, such as educational level, work complexity
      and cognitive activity in these processes. A model is also presented that argues
      that people with MCI and low reserves show a steeper decline early in the process
      of deterioration, compared to the high level of reserve this marked deterioration
      would have at the end of the process, due to the protective role of this reserve.
      This raises the need for more empirical research to help consolidate this
      theoretical model.

PMID- 22633250
TI  - [Pharmacological treatment of dementia: when, how and for how long.
      Recommendations of the Working Group on Dementia of the Catalan Society of
      Geriatrics and Gerontology].
AB  - Dementia in general--and Alzheimer's disease (AD) in particular--are bound to
      loom large among the most acute healthcare, social, and public health problems of
      the 21st century. AD shows a degenerative progression that can be slowed down-
      yet not halted--by today's most widely accepted specific treatments (those based
      on cholinesterase inhibitors as well as those using memantine). There is enough
      evidence to consider these treatments advisable for the mild, moderate and severe
      phases of the illness. However, in the final stage of the disease, a decision has
      to be made on whether to withdraw such treatment or not. In this paper, the
      Working Group on Dementia for the Catalan Society of Geriatrics and Gerontology
      reviews the use of these specific pharmacological treatments for AD, and, drawing
      on the scientific evidence thus gathered, makes a series of recommendations on
      when, how, and for how long, the currently existing specific pharmacological
      treatments should be used.

PMID- 22633251
TI  - The effect of a low and high resource intervention on older drivers' knowledge,
      behaviors and risky driving.
AB  - This study aimed to compare an in-class Seniors on the MOVE (Mature Operators
      Vehicular Education) interactive multi-session driving curriculum with a self
      guided MOVE curriculum for older adults. Using a two group randomized design, we
      sought to determine if there are between-group differences in older drivers'
      knowledge and safety behaviors among participants. Forty-four participants with
      an average age of 79 years (SD=7.1) were randomly assigned to the original MOVE
      program (SOM-A) or a lower resource (SOM-B) self-guided intervention. SOM-A is a
      four session program designed to improve older drivers safety knowledge and
      better understand skills for safer driving. SOM-B is a self-guided program with
      one required in-class session and one optional session. Subsequent to completion
      of both curricula, participants were offered CarFit, a comprehensive check of how
      well a senior driver and their vehicle work together. Baseline, post-intervention
      and 6-month follow up questionnaires were completed by participants. We found
      significant differences (p=.01) in the mean driving safety knowledge scores when
      comparing participants in SOM-A (3.7, SD 2.0) to those in SOM-B (0.87, SD 2.6).
      With regard to behavioral outcomes, we focused on always wearing a seatbelt,
      talking with a health care provider about driving ability, and sitting 10-12
      inches from the steering wheel. The vast majority of participants reported always
      wearing their seat belts (SOM-A 100%, SOM-B 92%, p=1.0), and very few reported
      talking with their doctors (SOM-A Baseline--0%, Follow up 1--0%, p=n/a). Mean
      behavior change scores for participants sitting 10-12 inches from the steering
      wheel were significantly more likely among SOM-A (mean=.65, SD=.5) participants
      than those in SOM-B (mean=.29, SD=.5, p=.01) at first follow-up. Taken together,
      these findings suggest that the more intensive program is more effective and that
      driving safety programs focused on behaviors to self evaluate driving abilities
      continue to be needed to help older drivers remain safer on the road as they age.
      The involvement of health care providers in such efforts may be an untapped
      potential.

PMID- 22633252
TI  - Factors related to seatbelt-wearing among rear-seat passengers in Malaysia.
AB  - The benefit of wearing a rear seatbelt in reducing the risk of motor vehicle
      crash-related fatalities and injuries has been well documented in previous
      studies. Wearing a seatbelt not only reduces the risk of injury to rear-seat
      passengers, but also reduces the risk of injury to front-seat occupant who could
      be crushed by unbelted rear-seat passengers in a motor vehicle crash. Despite the
      benefits of wearing a rear seatbelt, its rate of use in Malaysia is generally
      low. The objective of this study was to identify factors that are associated with
      the wearing of a seatbelt among rear-seat passengers in Malaysia. Multinomial
      logistic regression analysis of the results of a questionnaire survey of 1651
      rear-seat passengers revealed that rear-seat passengers who were younger, male,
      single and less educated and who had a perception of a low level of legislation
      enforcement, a lower risk-aversion and less driving experience (only for
      passengers who are also drivers) were less likely to wear a rear seatbelt. There
      was also a significant positive correlation between driver seatbelt and rear
      seatbelt-wearing behaviour. This implies that, in regards to seatbelt-wearing
      behaviour, drivers are more likely to adopt the same seatbelt-wearing behaviour
      when travelling as rear-seat passengers as they do when driving. These findings
      are crucial to the development of new interventions to increase the compliance
      rate of wearing a rear seatbelt.

PMID- 22633253
TI  - Investigation of models for relating roundabout safety to predicted speed.
AB  - Despite widespread recognition of operating speed as a key safety-related
      variable for roundabouts, there is no consensus on the best models for capturing
      the relationship between crashes and speed, or, for that matter, on how speed can
      be estimated in situations where it cannot be observed (such as when a roundabout
      is being designed or redesigned). This paper uses US and Italian roundabout
      approach-level data to investigate models relating safety to various measures of
      predicted speed. This is an indirect approach for developing safety models for
      estimating the effects of design features, the premise being that these features
      can better predict speed, which, in turn, can be used as a predictor of crash
      frequency. After exploring various possibilities, the approach average speed
      (AAS) - defined as the average of entry, upstream circulating and exiting speeds
      in this study - was found to be the speed measure that best predicts safety. US
      data were used to develop a Bayesian Poisson-gamma safety model based on
      predicted AAS with random coefficients and varying dispersion parameter. This
      model structure was not appropriate for the Italian data used to examine whether
      the approach could be generalized to data for another country. For that data, a
      zero-inflated Poisson (ZIP) model was found to be suitable. Notwithstanding the
      heterogeneity of the model structure, the investigation suggests that the
      indirect approach for evaluating the safety of a roundabout is a sound one in
      that it can preserve model parsimony while capturing the effects of design
      changes that affect safety.

PMID- 22633254
TI  - Validation of intracerebral hemorrhage-specific intensity of care quality
      metrics.
AB  - BACKGROUND: Given the considerable variation in care of patients with
      intracerebral hemorrhage (ICH) among centers that results in differences in
      outcome among these patients, a new intensity of care quality metrics has been
      proposed. This study aimed to validate the new ICH-specific intensity of care
      quality metrics. METHODS: A total of 50 consecutive patients with ICH who were
      admitted within 24 hours of symptom onset were identified. Twenty-six quality
      indicators related to 18 facets of care were incorporated into a metric providing
      the variable, definition of the variable, and quality parameter. A score of 1
      point was assigned if the quality parameter met the threshold for appropriate
      performance or if the parameter was not applicable, creating a total score of up
      to 26 points. The predictive validity of the classification scheme was tested by
      using the bootstrap method. RESULTS: Fourteen of the 50 patients with ICH died
      during hospitalization (28%). The intensity of care quality metric score ranged
      from 17 points to 26 points. The mean score was higher in those who survived
      compared with those who died (23 +/- 3 vs 21 +/- 2; P = .02). Survival increased
      with tertile based on higher scores (100%, 67%, and 55%; P = .017). The receiver
      operating characteristic curve demonstrated a high discriminating ability of
      intensity of care quality metrics for in-hospital mortality (0.730, 95%
      confidence interval, 0.591-0.869) and a C-statistic of 0.91 (95% confidence
      interval, 0.90-0.92). CONCLUSIONS: Correlation of the new ICH-specific intensity
      of care quality metric with in-hospital mortality supports its broader use for
      improving and standardizing medical care among patients with ICH.

PMID- 22633255
TI  - High singleton live birth rate confirmed after ovulation induction in women with
      anovulatory polycystic ovary syndrome: validation of a prediction model for
      clinical practice.
AB  - OBJECTIVE: To evaluate the cumulative singleton live birth rate after classic
      ovulation induction in women with anovulatory polycystic ovary syndrome and to
      validate a previously developed prediction model. DESIGN: Prospective follow-up
      study. SETTING: Tertiary infertility unit. PATIENT(S): Validation cohort of 108
      treatment-naive anovulatory PCOS patients. INTERVENTION(S): Conventional
      ovulation induction, applying clomiphene citrate as first-line treatment,
      followed by exogenous gonadotropins as second-line intervention. MAIN OUTCOME
      MEASURE(S): Singleton live birth prediction. Model calibration and discrimination
      were assessed for the initial model (variables included age, duration of
      infertility, and insulin/glucose ratio) and a second model in which the
      insulin/glucose ratio was replaced by body mass index. RESULT(S): The cumulative
      singleton live birth rate after 12 and 24 months was 60% and 78%, respectively.
      Overall, the observed rates were higher than predicted: hazard ratio 1.21 (95%
      confidence interval [CI] 0.89, 1.64), first model and 1.25 (95% CI 1.20, 1.30),
      second model. However, the predictive capacity of the model variables was
      reliable, with calibration slopes of 0.79 (95% CI -0.04, 1.63) and 1.06 (95% CI
      0.95, 1.18), respectively. CONCLUSION(S): The present study confirms the
      previously reported good treatment prognosis for women with PCOS undergoing
      classic ovulation induction. Women with a poor prognosis, for whom alternative
      treatment options may be considered, can best be identified by a prediction model
      including age, duration of infertility, and body mass index. CLINICAL TRIAL
      REGISTRATION NUMBER: NCT00821379.

PMID- 22633256
TI  - Ten years' experience with an external quality control program for semen
      analysis.
AB  - OBJECTIVE: To gauge the performance of laboratories and impact of the German
      semen analysis external quality control program (QuaDeGA) over its first 10
      years. DESIGN: Retrospective analysis of QuaDeGA's twice yearly distribution of
      fixed semen samples and electronic material documenting sperm motility. Ranking
      of each participant's responses was determined according to their relation to a
      "target window." SETTING: Multicenter. PAITENT(S): Healthy donors.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Laboratory performance, World
      Health Organization (WHO) adherence. RESULT(S): Over 19 runs, there was a steady
      increase of participants (280 laboratories), the largest group being private
      urologic practices. Although use of WHO-recommended Neubauer chamber (from 33% to
      55%) and diluent (from 11% to 32%) increased, the opposite occurred with
      morphology staining protocols (from 41% to 19%). Overall, <8% of laboratories
      truly followed WHO guidelines. Median-based comparisons, replacing reference
      laboratories, resulted in a merging of performance rankings regardless of the
      protocols used. CONCLUSION(S): Adherence to WHO recommendations is low, with the
      majority of laboratories using methods expressly opposed by the guidelines.
      Participation in QuaDeGA was found to improve the performance of the laboratories
      involved in the program. However, the use of median-based ranking, while
      decreasing the extent of variance between laboratories, brings into question the
      significance of the rankings.

PMID- 22633257
TI  - Glutathione S-transferase genes and the risk of recurrent miscarriage in Italian
      women.
AB  - OBJECTIVE: To investigate the role of glutathione S-transferases (GSTs) in the
      pathogenesis of recurrent miscarriage (RM). DESIGN: Genetic association study.
      SETTING: University of Rome, Tor Vergata and San Giovanni Calibita,
      Fatebenefratelli Hospital. PATIENT(S): One hundred twenty-one women with RM and
      113 women without pregnancy complications. INTERVENTION(S): Genomic DNA extracted
      from buccal cells and screening of positive/null genotypes of GSTM1 and GSTT1
      genes and single nucleotide polymorphisms of GSTA1, GSTO2, and GSTP1 genes. MAIN
      OUTCOME MEASURE(S): Occurrence of GST polymorphisms. RESULT(S): Women with at
      least one GSTA1*-69T allele are more frequent in the RM group than in the control
      group: 67% vs. 48%, respectively. Significant outcomes were obtained considering
      different genetic models: codominant, dominant, and log-additive. In addition,
      the combined analysis suggests that GSTA1 and GSTM1 variants have a significant
      interaction in RM risk. CONCLUSION(S): Our study highlighted a significant
      association between the GSTA1 gene and an increased risk of RM. In particular,
      the -69T allele in the GSTA1 gene may be considered as a predisposing factor of
      RM.

PMID- 22633258
TI  - Sperm DNA fragmentation induced by cryopreservation: new insights and effect of a
      natural extract from Opuntia ficus-indica.
AB  - OBJECTIVE: To analyze the effect of cryopreservation on sperm DNA fragmentation
      (SDF) in two cytometric sperm populations, PI(brighter) and PI(dimmer), and to
      test the effects of Opuntia ficus-indica (OFI) extracts, which contain
      antioxidants and flavanoids, and of resveratrol on cryopreservation of human
      semen. DESIGN: In vitro prospective study. SETTING: Institutional study.
      PATIENT(S): Twenty-one normozoospermic men undergoing semen analysis for couple
      infertility. INTERVENTION(S): Cryopreservation using the routine method in the
      presence of OFI extracts or resveratrol. MAIN OUTCOME MEASURE(S): Measurement of
      SDF by TUNEL/PI flow cytometric method to evaluate sperm motility (by automated
      motion analysis, CASA system) and viability (by eosin/nigrosin staining) in the
      two populations of sperm PI(br) and PI(dim). RESULT(S): Cryopreservation induced
      an increase of SDF only in the PI(br) sperm population. The increase was
      negatively dependent on the basal values of SDF in the same population. Addition
      of OFI extracts and resveratrol to the cryopreservation medium slightly but
      statistically significantly reduced SDF in the PI(br) population without
      affecting the deleterious effect of cryopreservation on sperm motion parameters
      or viability. CONCLUSION(S): The increase of SDF in the PI(br) population, which
      is unrelated to semen quality, suggests that caution must be taken in using
      cryopreserved semen, as morphologically normal and motile sperm may be damaged.
      The addition of substances with multifunctional properties such as OFI extracts
      to cryopreservation medium is only slightly effective in preventing the dramatic
      effects on SDF.

PMID- 22633259
TI  - Effects of malignancies on the gonadal function.

PMID- 22633260
TI  - Characterization of two heterozygous mutations of the oocyte activation factor
      phospholipase C zeta (PLCzeta) from an infertile man by use of minisequencing of
      individual sperm and expression in somatic cells.
AB  - OBJECTIVE: To examine the underlying factors leading to infertility in a male
      patient from whom phospholipase C zeta H398P (PLCzeta(H398P), histidine >
      proline) and PLCzeta(H233L) (histidine > leucine) mutations were previously
      identified. DESIGN: Laboratory-based study. SETTING: University laboratory.
      PATIENT(S): An infertile 38-year-old man with significantly impaired oocyte
      activation ability. INTERVENTION(S): Minisequencing of individual sperm for
      PLCzeta(H398P) and PLCzeta(H233L), and investigation of localization patterns
      arising from the expression of fluorescently tagged PLCzeta isoforms in HEK293T
      cells. MAIN OUTCOME MEASURE(S): The presence/absence of PLCzeta(H398P) and
      PLCzeta(H233L) determined in individual sperm (n = 12 sperm), and localization of
      fluorescent mutant PLCzeta isoforms quantified in HEK293T cells. RESULT(S): Sperm
      possessed either PLCzeta(H233L) or PLCzeta(H398P), but never both at the same
      time. Fluorescent PLCzeta(H233L) and PLCzeta(H233L+H398P) (both mutations
      together) localized to discrete regions in HEK293T cytoplasm but not the plasma
      membrane. Fluorescence statistically significantly varied between constructs such
      that PLCzeta(WT) > mutant isoforms at both 48- and 56-hour time points.
      Fluorescent-PLCzeta(H233L+H398P) exhibited a statistically significantly reduced
      level of fluorescence compared with PLCzeta(H398P) at 48 hours but not 56 hours.
      CONCLUSION(S): Both H398P and H233L mutations are present on different alleles
      and do not alter PLCzeta localization in HEK293T cells. Loss-of-activity
      mutations in PLCzeta may contribute not only toward male infertility but also
      male subfertility in cases where PLCzeta is mutated on a single allele.

PMID- 22633261
TI  - The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian
      endometriosis.
AB  - OBJECTIVE: To understand the role of ectopic endometriotic stromal cells in
      ovarian endometriosis (OEM) and the associated risks for infertility and
      carcinogenesis. DESIGN: Analyses of secreted proteins and gene expression using
      immortalized eutopic/ectopic endometrial(-otic) stromal cells from OEM. SETTING:
      University. PATIENT(S): Women with and without OEM. INTERVENTION(S): Samples of
      endometrial(-otic) tissue from women with or without OEM. MAIN OUTCOME
      MEASURE(S): Immunohistochemical analysis of oxidative stress in OEM, gene
      expression profiles, and the identification of secreted proteins by mass
      spectrometry in immortalized endometrial(-otic) stromal cells. RESULT(S): 4
      Hydroxy-2-nonenal-modified proteins and carboxymethyllysine were abundant in the
      stroma, rather than epithelia, of OEM patients, indicating the presence of
      oxidative stress. Immortalized ectopic endometriotic stromal cells exhibited high
      IRP1/IRP2/HIF-1beta expression and contained lower amounts of iron and copper
      than their eutopic counterparts. Expression profiles, in combination with protein
      identification, revealed that complement component 3 (C3) and pentraxin-3 (PTX3)
      are the major proteins secreted from immortalized ectopic endometriotic stromal
      cells. Complement-3/PTX3 promoted the secretion of various cytokines by THP1
      macrophage cells and thus supported M1 differentiation. CONCLUSION(S):
      Immortalized ectopic endometriotic stromal cells in OEM predominantly secrete C3
      and PTX3 and exhibit a differential regulation of iron metabolism.

PMID- 22633262
TI  - Age-associated alteration of oocyte-specific gene expression in polar bodies:
      potential markers of oocyte competence.
AB  - OBJECTIVE: To confirm that oocyte-specific messenger RNAs are detectable in the
      polar body (PB) of metaphase II (MII) oocytes and determine the effect of age on
      oocyte-specific transcript levels. DESIGN: Prospective study. SETTING: Hospital
      based academic research laboratory. ANIMAL(S): CD1 female mice. INTERVENTION(S):
      Aged (40-50 weeks) and young (7-9 weeks) mice were administered pregnant mare
      serum gonadotropin (PMSG) and hCG. Oocytes were fertilized in vitro to assess
      fertilization and developmental competence. The MII oocytes were obtained and
      first PBs were removed. Messenger RNAs from each PB and its sibling oocyte were
      reverse transcribed and analyzed by real-time quantitative polymerase chain
      reaction (PCR). MAIN OUTCOME MEASURE(S): Fertilization and developmental rates
      and expression of six oocyte-specific genes (Bmp15, Gdf9, H1foo, Nlrp5, Tcl1, and
      Zp3) in PBs and sibling oocytes from young versus aged mice. RESULT(S): Oocytes
      from aged mice had lower developmental competence. Four genes (H1foo, Nlrp5,
      Tcl1, and Zp3) were differentially expressed in aged versus young oocytes. All
      six transcripts were present in PBs from aged and young mice at lower levels than
      in the sibling oocytes; transcript levels were lower in aged PBs compared with
      young PBs. CONCLUSION(S): There is a significant difference in the transcript
      levels of oocyte-specific genes in aged versus young PB that correlates with age
      related decreases in oocyte competence. Differences in gene expression in PB may
      be potential biomarkers of MII oocyte competence.

PMID- 22633263
TI  - Cumulative newborn rates increase with the total number of transferred embryos
      according to an analysis of 15,792 ovum donation cycles.
AB  - OBJECTIVE: To measure the success of in vitro fertilization (IVF) of donated ova
      according to cumulative newborn rates (CNBR) per number of embryos required to
      achieve at least one newborn (EmbR), considering in addition the relevance of age
      and infertility etiology. DESIGN: Survival curves and Kaplan-Meier methods were
      employed to analyze CNBR with respect to the number of EmbR in a retrospective
      cohort of oocyte donation recipients. SETTING: University-affiliated infertility
      center. PATIENT(S): Infertile couples undergoing IVF with oocyte donation.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): CNBR per EmbR. RESULT(S): The
      CNBR increased radically (up to 64.8%) between 1 and 5 EmbR, moderately (85.2%)
      between 5 and 15, and slowly thereafter, reaching a plateau at 15 embryos (92.4%)
      and peaking after 25 EmbR (96.8%), thus demonstrating that the chances of success
      vary as failed attempts accumulate. Patient age was not a negative factor, and
      indication for oocyte donation was also irrelevant to the outcome. The data
      showed an overall mean number of 2.6 embryo transfers and 5.8 transferred embryos
      per newborn. CONCLUSION(S): The relationship between CNBR and number of EmbR
      provides pragmatic and exact information about the probability of success with
      oocyte donation, which is of obvious relevance to patient counseling.

PMID- 22633264
TI  - New candidate genes to predict pregnancy outcome in single embryo transfer cycles
      when using cumulus cell gene expression.
AB  - OBJECTIVE: To relate the gene expression in cumulus cells surrounding an oocyte
      to the potential of the oocyte, as evaluated by the embryo morphology (days 3 and
      5) and pregnancy obtained in single-embryo transfer cycles. DESIGN: Retrospective
      analysis of individual human cumulus complexes using quantitative real-time
      polymerase chain reaction for 11 genes. SETTING: University hospital IVF center.
      PATIENT(S): Thirty-three intracytoplasmic sperm injection patients, of which 16
      were pregnant (4 biochemical and 12 live birth). INTERVENTION(S): Gene expression
      analysis in human cumulus complexes collected individually at pickup, allowing a
      correlation with the outcome of the corresponding oocyte. Multiparametric models
      were built for embryo morphology parameters and pregnancy prediction to find the
      most predictive genes. MAIN OUTCOME MEASURE(S): Gene expression profile of 99
      cumulus complexes for 11 genes. RESULT(S): For embryo morphology prediction,
      TRPM7, ITPKA, STC2, CYP11A1, and HSD3B1 were often retained as informative.
      Models for pregnancy-biochemical or live birth-complemented or not with patient
      and cycle characteristics, always retained EFNB2 and CAMK1D together with STC1 or
      STC2. Positive and negative predictive values of the live birth models were >85%.
      CONCLUSION(S): EFNB2 and CAMK1D are promising genes that could help to choose the
      embryo to transfer with the highest chance of a pregnancy.

PMID- 22633265
TI  - Subtle progesterone rise on the day of human chorionic gonadotropin
      administration is associated with lower live birth rates in women undergoing
      assisted reproductive technology: a retrospective study with 2,555 fresh embryo
      transfers.
AB  - OBJECTIVE: To evaluate the association between serum P levels on the day of hCG
      administration and pregnancy outcome in women undergoing controlled ovarian
      hyperstimulation, prevention of premature ovulation by GnRH analogues, and fresh
      ET after 5 days of embryo culture. DESIGN: Retrospective, observational, cohort
      study. SETTING: Private IVF center. PATIENT(S): A total of 2,555 women undergoing
      fresh ET on day 5 in 2,062 GnRH agonist and 493 GnRH antagonist cycles.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth rate. RESULT(S): Live
      birth rate in cycles with GnRH agonists was significantly lower in women with P
      levels >= 2.0 ng/mL (17.4%) on the day of hCG administration as compared with
      women with P levels <1.5 ng/mL (24.6%) and 1.5-1.99 ng/mL (26.7%). No such
      significant differences in live birth rates in cycles with GnRH antagonist could
      be observed. CONCLUSION(S): A rise of serum P levels >= 2.0 ng/mL on the day of
      hCG administration is associated with impaired early embryo implantation and
      reduced live birth rate in cycles with GnRH agonists after day-5 fresh ET.

PMID- 22633266
TI  - Preterm delivery and low birth weight in singleton pregnancies conceived by women
      with and without a history of infertility.
AB  - OBJECTIVE: To determine predictors of low birth weight (LBW) and preterm delivery
      (PTD) in singleton pregnancies conceived by women with and without a history of
      infertility. DESIGN: Retrospective cohort study. SETTING: Eleven infertility
      clinics in northern California. PATIENT(S): Three groups of women who carried
      singleton pregnancies to >=20 weeks' gestation: 542 infertile women who conceived
      after treatment, 441 infertile women who conceived spontaneously, and 1,008
      fertile women for comparison. INTERVENTION(S): Chart review. MAIN OUTCOME
      MEASURE(S): Association of LBW or PTD with infertility treatment, maternal age,
      parity, obesity, or development of gestational diabetes. RESULT(S): Infertile
      women who conceived with treatment were more likely to be obese, develop
      gestational diabetes, and have ovarian, ovulatory, or male factor infertility
      than infertile women who conceived spontaneously. Infertile women who conceived
      after treatment had 1.61 times greater odds of having an LBW infant. Nulliparity
      was an independent predictor of LBW and PTD in all three groups after controlling
      for maternal age, history of infertility, infertility treatment, obesity, and
      gestational diabetes. CONCLUSION(S): Nulliparous women and women with a history
      of infertility who conceive a singleton after treatment may be at increased odds
      for having an LBW infant. Infertile women do not appear to be at increased odds
      for PTD.

PMID- 22633267
TI  - Measurement of postvoid residual urine in conscious mice using high-frequency
      transrectal ultrasound.
AB  - The aim of this study was to develop a novel technique for a minimally invasive
      ultrasound measurement of postvoid residual urine (PVR) in conscious mice using a
      miniature ultrasound probe and a transrectal approach. The PVR was determined by
      the ellipsoid formula in the maximum sectional image of the bladder visualized
      with a 20-MHz ultrasound probe (2 mm in diameter) inserted into the rectum. The
      accuracy, including the intra- and interobserver reproducibilities, of the
      ultrasonic PVR measurements (in 10 5- to 50-week-old mice) was evaluated, which
      revealed excellent internal consistency. In M(3) muscarinic acetylcholine
      receptor knockout male mice, a chronological evaluation of the PVR identified
      abnormal urinary retention present at infancy and exacerbated with aging,
      suggesting significant voiding dysfunction. Our technique for the measurement of
      PVR in conscious mice was accurate and useful for identifying the voiding
      dysfunction in mice.

PMID- 22633268
TI  - Low-intensity pulsed ultrasound (LIPUS) may prevent polyethylene induced
      periprosthetic osteolysis in vivo: a novel molecular mechanism.

PMID- 22633269
TI  - High-intensity focused ultrasound tumor ablation activates autologous tumor
      specific cytotoxic T lymphocytes.
AB  - Previous studies have shown that high-intensity focused ultrasound (HIFU)
      ablation can enhance host antitumor immune response, though the mechanism is
      still unknown. In the present study, we investigated whether HIFU ablation could
      activate tumor-specific T lymphocytes and then induce antitumor cellular
      immunity. We studied 70 C57BL/6J mice bearing the H(22) tumor; they were randomly
      divided into a HIFU group and a sham-HIFU group. Of the mice, 35 in the HIFU
      group underwent HIFU ablation of the H(22) hepatic tumor, and the remaining 35
      received a sham-HIFU procedure. In addition, 35 female, naive syngeneic C57BL/6J
      mice were used as controls. All mice were sacrificed 14 days after HIFU, and the
      spleens were harvested. The function of T lymphocytes was determined. As a
      valuable tool for detecting and characterizing peptide-specific cells, the
      frequency of MHC class I tetramer/CD8-positive cells was quantified, which could
      help to determine the response and number of T lymphocytes. The therapeutic
      effect of the HIFU-activated lymphocytes on tumor-bearing mice was investigated
      after adoptive transfer of the lymphocytes. The results showed that compared to
      sham-HIFU and control groups, HIFU ablation significantly increased the
      cytotoxicity of cytotoxic T lymphocytes (p < 0.05), with a significant increase
      of IFN-gamma and TNF-alpha secretion (p < 0.001). The frequency of the MHC class
      I tetramer/CD8-positive cells was significantly higher in the HIFU group (p <
      0.05). A stronger inhibition of tumor progression and higher survival rates were
      observed to be significant after adoptive immunotherapy in the HIFU group as
      compared to the sham-HIFU and control groups (p < 0.01). It is concluded that
      HIFU ablation could activate tumor-specific T lymphocytes, thus inducing
      antitumor cellular immune responses in tumor-bearing mice.

PMID- 22633270
TI  - Universal maternal cervical length screening during the second trimester: pros
      and cons of a strategy to identify women at risk of spontaneous preterm delivery.
AB  - Three large randomized controlled trials investigating the efficacy of universal
      cervical length screening and treatment with vaginal progesterone or cervical
      cerclage to prevent preterm delivery have been published over the past several
      years. None of these trials demonstrate proven efficacy for universal cervical
      length screening and cerclage placement in women with short cervical length.
      However, universal cervical length screening and treatment with daily vaginal
      progesterone in women with short cervical length reduces the risk of preterm
      birth, but large numbers of women must be screened to prevent a relatively small
      number of preterm deliveries. Issues that should be considered while implementing
      universal cervical length screening include: (1) standards of quality and
      reproducibility for transvaginal ultrasound cervical length ascertainment; (2)
      implications of screening on the application of therapeutic strategies to
      populations not known to benefit (so-called "indication creep"); and (3)
      willingness of obstetricians to prescribe vaginal progesterone formulations that
      are not approved by the US Food and Drug Administration for preterm birth
      prevention. Optimal strategies to employ cervical ultrasound and progesterone
      treatment might be revealed by additional studies investigating cervical length
      cutoffs, frequency of screening, selective screening in higher-risk groups, and
      the use of transabdominal cervical length screening as a surrogate for
      transvaginal cervical length screening.

PMID- 22633271
TI  - Takayasu arteritis complicating pregnancy in adolescence.
AB  - Pregnant adolescent patients afflicted with Takayasu arteritis represent a
      clinical entity not seen by many. The care of such patients is often managed by
      multidisciplinary teams, where vascular surgeons are asked to provide input on
      cardiovascular implications during and after a pregnant state. Knowledge and
      understanding of the interaction between the two conditions allows for well
      informed decision making and favorable outcomes with pregnancy, as well as proper
      long-term follow-up and care with appropriate clinicians.

PMID- 22633272
TI  - Reduced levels of interleukin 33 and increased levels of soluble ST2 in subjects
      with amyotrophic lateral sclerosis.
AB  - Interleukin 33 (IL-33) is a cytokine that functions as an alarmin and is released
      from damaged tissue. The receptor for IL-33 is ST2, which exists as membrane
      bound and soluble forms. Levels of IL-33 and soluble ST2 (sST2) are elevated in
      some inflammatory diseases. Amyotrophic lateral sclerosis (ALS) is a disease that
      is due to loss of motor neurones, with some neuro-inflammation at the site of
      pathology. This study was performed to measure levels of IL-33 and sST2 in ALS.
      Serum was obtained from subjects with ALS (n=42) and healthy controls (n=38).
      Levels of IL-33 and s ST2 were measured with ELISA. The level of Il-33 was
      significantly lower in ALS subjects than healthy controls, and the levels of sST2
      were significantly higher. The lower levels of IL-33 could be due to degradation
      of IL-33 by caspases released from apoptotic cells. However the levels of IL-33
      could also be lower due to effects of sST2 which acts as a receptor for IL-33.
      The levels of sST2 could reflect inflammation in ALS.

PMID- 22633273
TI  - Immunomodulatory influence of bone marrow-derived mesenchymal stem cells on
      neuroinflammation in astrocyte cultures.
AB  - The therapeutic benefits associated with mesenchymal stem cells (MSCs) largely
      result from their immunomodulatory and neurotrophic properties. In this study, we
      evaluated the effects of MSCs on astrocyte cultures exposed to
      lipopolysaccharide. In response to this inflammatory trigger, astrocytes showed
      an increased expression of pro-inflammatory genes (IL-1beta, TNFalpha, IL-6),
      which was attenuated by pre-exposure to MSC conditioned medium. Furthermore,
      mediators released by MSCs increased cell proliferation and altered the
      regulation of intermediate filaments (GFAP, vimentin), pro-inflammatory enzymes
      (iNOS, COX-2) and receptors (TLR4, CD14, mGluR3, mGluR5). These data demonstrate
      that MSCs influence diverse cell types participating in the response to
      neuroinflammation.

PMID- 22633274
TI  - Decreased serum levels of nucleolin protein fragment, as analyzed by bead-based
      proteomic technology, in multiple sclerosis patients compared to controls.
AB  - In order to investigate the biomarkers associated with relapsing-remitting
      multiple sclerosis (RRMS), we analyzed 72 patients with RRMS and 65 healthy
      controls using proteome technology. Peptides in sera were purified using magnetic
      beads, and analyzed by matrix-assisted laser desorption ionization time-of-flight
      (MALDI-TOF) mass spectrometry and ClinProTool software. Thirteen peptides were
      significantly different between patients with RRMS and healthy controls.
      Furthermore, a pattern of peaks was selected for genetic algorithm (GA),
      supervised neural network (SNN) and quick classifier (QC) model building. Among
      these three models, GA method was best with 93.49% of recognition capability and
      82.66% of cross-validation and discriminated the proteomic spectra in patients
      with RRMS from healthy controls, with a sensitivity of 80% and a specificity of
      91.3%. Meanwhile, the first peptide with m/z 2023.3 was identified as fragment of
      nucleolin protein. There is a possible relationship between the fragment peptide
      of nucleolin and the trigger of relapse in MS. Sera nucleolin may serve as a
      possible biomarker of RRMS.

PMID- 22633275
TI  - Outbreak of cutaneous zygomycosis associated with the use of adhesive tape in
      haematology patients.
AB  - We report an outbreak of cutaneous Rhizopus oryzae infection associated with
      adhesive polyethylene tapes used to stabilize peripheral venous catheters in four
      patients. All patients were suffering from haematological diseases; the infection
      severity was proportional to the duration of neutropenia. Intervention with
      systemic antifungal treatment and surgical debridement was required for
      resolution of the infection. The entire batch of tapes was withdrawn and the
      outbreak subsided.

PMID- 22633276
TI  - Role of occupational health staff in investigation of invasive group A
      streptococcal infection hospital outbreak.
AB  - Healthcare workers (HCWs) are commonly implicated as index cases during
      investigation of invasive group A streptococcus (GAS) hospital outbreaks. Staff
      screening may be needed but guidelines on implementation vary. We conducted an
      analysis to find common exposures in patients infected with a rare type of GAS
      and staff were asked to self-screen. Swabs were negative, but as the outbreak
      continued, specific HCWs were asked to attend the occupational health department.
      The index case was then identified as having a skin disorder infected with same
      rare GAS. We describe the importance of occupational health clinical review of
      HCWs during an outbreak.

PMID- 22633277
TI  - Epidemiological survey of Clostridium difficile ribotypes in the North East of
      England during an 18-month period.
AB  - During an 18-month period, 1606 stool specimens from laboratory-confirmed cases
      of Clostridium difficile infection in the North East of England were ribotyped
      using unrestricted polymerase chain reaction. Of these, 87.6% grew C. difficile
      on culture; 70% had one of 10 recognizable ribotypes of which 001, 106 and 027
      were the most prevalent. The proportions of ribotypes 002 and 015 declined during
      the study period, whereas ribotypes 016 and 023 increased. Ribotype 005 was
      significantly more numerous in males and ribotype 027 was associated with
      significantly higher mean age. Our findings differ from national data derived
      from more selective testing.

PMID- 22633278
TI  - When the user is not the chooser: learning from stakeholder involvement in
      technology adoption decisions in infection control.
AB  - BACKGROUND: Health systems need efficient and effective innovation decisions to
      provide maximum benefit to patients, particularly in a climate of financial
      constraints. Although evidence-based innovations exist for helping to address
      healthcare-associated infections, the uptake and implementation of these is
      highly variable and in some cases very slow. AIM: To investigate innovation
      adoption decisions and implementation processes from an organizational
      perspective, focusing on the implications of stakeholder involvement during the
      innovation process. METHODS: Thirty-eight technology adoption decisions and
      implementation processes were examined through 121 qualitative interviews in 12
      National Health Service healthcare organizations across England. FINDINGS:
      Stakeholder involvement varied across organizations with decisions highly
      exclusive to the infection prevention and control (IPC) team, to highly inclusive
      of wider organizational members. The context, including organizational culture,
      previous experience, and logistical factors influenced the level of stakeholder
      engagement. The timing of stakeholder involvement in the process impacted on: (i)
      the range of innovations considered; (ii) the technologies selected, and (iii)
      the success of technology implementation. Cases of non-adoption, discontinued
      adoption, and of successful implementation are presented to share learning. The
      potential benefits of stakeholder involvement for 'successful' innovation
      adoption are presented including a goal-oriented framework for involvement.
      CONCLUSIONS: Key stakeholder involvement can lead to innovation adoption and
      implementation compatible with structural and cultural contexts, particularly
      when involvement crosses the phases of initiation, decision-making and
      implementation. Involving members of the wider healthcare organization can raise
      the profile of IPC and reinforce efforts to make IPC everybody's business.

PMID- 22633279
TI  - UK laboratory diagnosis of Clostridium difficile infection: in a state of
      transition, confusion, or both?

PMID- 22633280
TI  - Physical activity and cardiovascular risk factors in Spanish children aged 11-13
      years.
AB  - INTRODUCTION AND OBJECTIVES: The prevalence of childhood obesity has increased in
      recent decades. The aim was to determine whether a 3-month intervention on daily
      physical activity at school could affect body weight and cardiovascular risk
      factors associated with childhood obesity. METHODS: A total of 137 children
      (12[1] years old) volunteered to participate in an observational cross-sectional
      study. Children were allowed to join one of the following groups: a) sedentary
      group (2h/week of physical education at school); b) active group (2h/week of
      physical education at school plus 3h/week extra physical activity), and c) sports
      group (2h/week of physical education at school plus 5h/week extra physical
      activity). Anthropometric characteristics, blood pressure, physical condition
      (estimated by the Course-Navette test), and biochemical parameters related with
      cardiovascular risk factors were determined. RESULTS: Body weight, body mass
      index, waist circumference, sum of skinfold thickness, body fat percentage, and
      fat mass index of children were decreased with high physical activity level,
      whereas body water content significantly increased with activity. Parameters
      related with cardiovascular risk -triglycerides, insulin, systolic blood
      pressure, and homeostatic model assessment index- presented lower values in the
      sports group. Maximal oxygen uptake and maximum heart rate (Course Navette test)
      progressively increased with activity. Children participating in a total of
      7h/week of physical activity presented significantly lower odds ratio of having
      high levels of the following cardiovascular risk factors: waist circumference,
      fat mass index, and homeostatic model assessment index. CONCLUSIONS: Physical
      activity is important for metabolic health in children. Children with higher
      levels of physical activity presented better anthropometric and biochemical
      profiles.

PMID- 22633281
TI  - Identification and characterization of the human leiomyoma side population as
      putative tumor-initiating cells.
AB  - OBJECTIVE: To isolate and characterize human leiomyoma stem cells by the side
      population (SP) method. DESIGN: Prospective experimental human and animal study.
      SETTING: University research laboratory-affiliated infertility clinic.
      PATIENT(S): Women undergoing laparoscopic myomectomy. ANIMAL(S): Female non-obese
      diabetic severe combined immune deficiency (NOD-SCID) mutation mice.
      INTERVENTION(S): Obtainment of human leiomyoma SP cells as candidate tumor
      initiating cells and establishment of two leiomyoma SP lines. MAIN OUTCOME
      MEASURE(S): Flow cytometry, semiquantitative polymerase chain reaction,
      clonogenicity assays, cDNA microarrays hybridization, cell culture, karyotype,
      molecular analysis, immunocytochemistry, in vitro differentiation,
      xenotransplantation assays, immunohistochemistry. RESULT(S): SP cells from human
      leiomyomas were isolated, identified, and characterized. Two leiomyoma's SP cell
      lines with a normal karyotype were thus established. Undifferentiated status was
      confirmed by the expression of OCT-4, NANOG, DNMT3B, GDF3. Presence of typical
      mesenchymal markers (CD90, CD105, CD73) and absence of hematopoietic stem cell
      markers (CD34, CD45) supported their mesodermal origin. Mesenchymal lineage
      commitment was also demonstrated by their ability to differentiate in vitro into
      adipogenic and osteogenic lineages. Finally, their functional capability was
      established in an animal model by leiomyoma tissue reconstruction. CONCLUSION(S):
      SP cells from human leiomyoma exhibit key features of tumor-initiating cells,
      opening up new possibilities of understanding the origin and developing new
      nonsurgical approaches for leiomyomas.

PMID- 22633282
TI  - Altered expression of apoA-I, apoA-IV and PON-1 activity in CBS deficient
      homocystinuria in the presence and absence of treatment: possible implications
      for cardiovascular outcomes.
AB  - Classical homocystinuria (HCU) is caused by mutations in cystathionine beta
      synthase (CBS) which, if untreated, typically results in cognitive impairment,
      thromboembolic complications and connective tissue disturbances. Paraoxonase-1
      (PON1) and apolipoprotein apoA-I are both synthesized in the liver and contribute
      to much of the cardioprotective effects of high density lipoprotein.
      Additionally, apoA-I exerts significant neuro-protective effects that act to
      preserve cognition. Previous work in a Cbs null mouse model that incurs
      significant liver injury, reported that HCU dramatically decreases PON1
      expression. Conflicting reports exist in the literature concerning the relative
      influence of homocysteine and cysteine upon apoA-I expression. We investigated
      expression of PON1 and apoA-I in the presence and absence of homocysteine
      lowering therapy, in both the HO mouse model of HCU and human subjects with this
      disorder. We observed no significant change in plasma PON1 paraoxonase activity
      in either mice or humans with HCU indicating that this enzyme is unlikely to
      contribute to the cardiovascular sequelae of HCU. Plasma levels of apoA-I were
      unchanged in mice with mildly elevated homocysteine due to CBS deficiency but
      were significantly diminished in both mice and humans with HCU. Subsequent
      experiments revealed that HCU acts to dramatically decrease apoA-I levels in the
      brain. Cysteine supplementation in HO mice had no discernible effect on plasma
      levels of apoA-I while treatment to lower homocysteine normalized plasma levels
      of this lipoprotein in both HO mice and humans with HCU. Our results indicate
      that plasma apoA-I levels in HCU are inversely related to homocysteine and are
      consistent with a plausible role for decreased expression of apoA-I as a
      contributory factor for both cardiovascular disease and cognitive impairment in
      HCU.

PMID- 22633283
TI  - Is shortened sleep duration a risk factor for overweight and obesity during
      adolescence? A review of the empirical literature.
AB  - This paper reviews 15 adolescent (10-19 yrs) studies that have directly
      investigated the effects of shortened sleep duration on overweight and obesity.
      The research studies included in this review inconsistently found significant
      effects between shortened sleep duration and weight status. This heterogeneity in
      study findings largely resulted from variability in study design, gender, and the
      method used to measure sleep duration. Consequently, due to the conflicting
      research findings, it remains inconclusive as to whether shortened sleep is a
      risk factor for overweight or obesity during adolescence. This review also
      identified methodological limitations within the literature and presented
      alternative methodologies for future research. First, sleep duration measures
      were identified that had questionable reliability and were possibly less accurate
      than other recommended sleep measurements. Second, 92% of cross-sectional studies
      found a significant relationship, yet 0% of prospective studies did. Third, the
      vast majority of studies neglected to statistically adjust for co-contributions
      from depression, and approximately half of the studies considered the role of
      physical activity. Recommendations for future research directions are presented
      which may help to clarify the conflicting findings and address the methodological
      concerns identified within this topical area.

PMID- 22633284
TI  - Comparison of supine-only and REM-only obstructive sleep apnoea.
AB  - OBJECTIVES: The effect of body position and sleep state on sleep apnoea have
      major clinical implications in the management of patients, yet are infrequently
      reported in the scientific literature. The aim of this study was to compare and
      contrast the prevalence and severity of supine-only and rapid eye movement (REM)
      only obstructive sleep apnoea (OSA) in a population. METHODS: Prospective cohort
      analysis of the influence of supine body position and REM sleep on the severity
      of apnoea in 100 consecutive patients with OSA (apnoea-hypopnoea index [AHI]>5)
      using attended polysomnography with continuous digital monitoring in an
      accredited sleep laboratory. Supine-only OSA was defined as a supine:non-supine
      AHI ratio of >2:1 and non-supine AHI <5 events/h. REM-only OSA was defined as an
      REM:non-REM ratio of >2:1 and non-REM AHI <5events/h. RESULTS: Supine sleep time
      represented a greater proportion of total sleep time than REM sleep time (40% vs
      13%). The prevalence of supine-only OSA was more than twofold greater than that
      of REM-only OSA (23% and 10%, respectively). The supine-only group had greater
      overall AHI (mean 12.6+/-6.1 vs 7.2+/-2.2 events/h; P<0.01) than the REM-only
      group. No significant differences in gender, age, or sleepiness were found
      between the two groups. CONCLUSIONS: Supine-only OSA is more common and is
      associated with a greater AHI than REM-only OSA.

PMID- 22633285
TI  - Association of IL-4 receptor gene polymorphisms with high density lipoprotein
      cholesterol.
AB  - The aim of this study is to investigate the correlation between E400A
      polymorphisms of interleukin-4 receptor alpha chain (IL-4Ralpha) and lipid
      metabolism. Genomic DNA from 121 type 2 diabetes mellitus (T2DM) patients and 113
      non-diabetic, non-obese control study subjects were extracted, and their IL
      4Ralpha E400A polymorphisms were analyzed by PCR-RFLP. The correlation between IL
      4Ralpha E400A genotypes and study subjects' lipid profile was then examined.
      Significant associations of the IL-4Ralpha E400A genotypes and high density
      lipoprotein-cholesterol (HDL-C) levels among control individuals (p=0.007), as
      well as among the T2DM patients (p=0.029), were observed. Significant
      correlations between IL-4Ralpha E400A genotypes with blood pressure, as well as
      with blood urea nitrogen, were also observed in control subjects. Our results
      reveal that IL-4Ralpha may play certain roles in the lipid metabolism of
      Taiwanese population and suggest a novel link between lipid metabolism and the
      cytokine receptor.

PMID- 22633286
TI  - The LIM-only protein FHL2 regulates interleukin-6 expression through p38 MAPK
      mediated NF-kappaB pathway in muscle cells.
AB  - Interleukin 6 (IL-6) is pleiotropic cytokine playing an important role in
      inflammatory response. Other than classical immune tissues, IL-6 is also produced
      in muscle cells under specific conditions. Four-and-a-half LIM-only protein 2
      (FHL2) is preferentially expressed in skeletal and cardiac muscle cells compared
      to other tissues indicating it has an important role in skeletal muscle and
      cardiovascular system. In this report, the regulation of IL-6 by FHL2 in muscle
      cells was investigated. We demonstrated that FHL2 overexpression increased IL-6
      mRNA level and its protein secretion in skeletal myoblasts. In contrast, the IL-6
      secretion was significantly decreased after FHL2-knockdown by siRNA in response
      to TNFalpha stimulation. We further showed that FHL2-mediated induction of IL-6
      was regulated by the activation of IL-6 promoter through stimulating NF-kappaB
      and p38 MAPK signaling pathway. Our results further illustrated the molecular
      mechanisms of IL-6 production, which provides new insights in the roles of FHL2
      in post-injury inflammation or cytoprotection of muscle cells.

PMID- 22633287
TI  - IL-5 and IL-17A are critical for the chronic IgE response and differentiation of
      long-lived antibody-secreting cells in inflamed tissues.
AB  - Prolonged survival of long-lived antibody-secreting cells in the BM has been
      implicated as a key component of long-term humoral immunity. The current study
      was designed to uncover the extrinsic signals required for the generation and
      maintenance of ASC in several niches (peritoneum, spleen and bone-marrow). Our
      results show that protein mixture of the Thalassophryne nattereri venom induced a
      chronic Th2 humoral response that is characterized by splenic hyperplasia with GC
      formation and venom retention by follicular DCs. Retention of B1a in the BM were
      observed. In the late phase (120d) of chronic venom-response the largest pool of
      ASC into the peritoneal cavity consisted of B220(neg)CD43(high) phenotype; the
      largest pool of ASC into spleen was constituted by B220 positive cells
      (B220(high) and B220(low)), whereas the largest pool of ASC into in the BM was
      constituted by the B220(high)CD43(low) phenotype; and finally, terminally
      differentiated cells (B220(neg)CD43(high)) were only maintained in the inflamed
      peritoneal cavity in late phase. After 120d a sustained production of cytokines
      (KC, IL-5, TNF-alpha, IL-6, IL-17A and IL-23) and leukocytes recruitment
      (eosinophils, mast cells, and neutrophils) were induced. IL-5- and IL-17A
      producing CD4+ CD44+ CD40L+ Ly6C+ effector memory T cells were also observed in
      peritoneal cavity. Finally, treatment of venom-mice with anti-IL-5- and anti
      IL17A-neutralizing mAbs abolished the synthesis of specific IgE, without
      modifying the splenic hyperplasia or GC formation. In addition, IL-5 and IL-17A
      negatively regulated the expansion of B1a in peritoneal cavity and BM, and
      promoted the differentiation of these cells in spleen. And more, IL-5 and IL-17A
      are sufficient for the generation of ASC B220(neg) in the peritoneal cavity and
      negatively regulate the number of ASC B220(pos), confirming that the hierarchical
      process of ASC differentiation triggered by venom needs the signal derived from
      IL-5 and IL-17A.

PMID- 22633288
TI  - Allicin protects against myocardial apoptosis and fibrosis in streptozotocin
      induced diabetic rats.
AB  - To evaluate the cardioprotective effect of allicin (AL) on myocardial injury of
      streptozotocin (STZ)-induced diabetic rats and to further explore its underlying
      mechanisms. Hyperglycemia was induced in rats by single intraperitoneal injection
      of STZ (40 mg/kg). Three days after STZ induction, the hyperglycemic rats (plasma
      glucose levels >= 16.7 mmol/l) were treated with AL by intraperitoneal injection
      at the doses of 4 mg/kg, 8 mg/kg, and 16 mg/kg daily for 28 days. The fasting
      blood glucose levels were measured on every 7th day during the 28 days of
      treatment. The body weight, blood glucose, and parameter of cardiac function were
      detected after 4 weeks to study the cardioprotective effects of AL on diabetic
      rats in vivo. The apoptotic index of cardiomyocytes was estimated by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The
      expressions of Fas, Bcl-2, CTGF, and TGF-beta(1) protein were studied by
      immunohistochemistry. Laser scanning confocal microscopy technique was utilized
      to observe the effects of AL on intracellular calcium concentration ([Ca(2+)](i))
      in rat ventricular cardiomyocytes. AL at the doses of 4 mg/kg, 8 mg/kg, and 16
      mg/kg significantly reduced blood glucose levels in a dose-dependent manner and
      increased body weight as well compared with the model group. Hemodynamic
      parameters including left ventricular systolic pressure (LVSP), left ventricular
      end-diastolic pressure (LVEDP), and maximum rate of left ventricular pressure
      rise and fall (+dp/dtmax and -dp/dtmax) were significantly restored back to
      normal levels in AL-treated (8 mg/kg and 16 mg/kg) rats compared with diabetic
      model rats. AL markedly inhibited cardiomyocyte apoptosis induced by diabetic
      cardiac injury. Further investigation revealed that this inhibitory effect on
      cell apoptosis was mediated by increasing anti-apoptotic protein Bcl-2 and
      decreasing pro-apoptotic protein Fas. Additional experiments demonstrated AL
      abrogated myocardial fibrosis by blocking the expressions of CTGF and TGF-beta(1)
      protein. AL shows protective action on myocardial injury in diabetic rats. The
      possible mechanisms were involved in reducing blood glucose, correcting
      hemodynamic impairment, reducing Fas expression, activating Bcl-2 expression,
      decreasing intracellular calcium overload, inhibiting the expressions of TGF
      beta(1) and CTGF, and further improving cardiac function.

PMID- 22633289
TI  - Neonatal soft tissue sarcomas.
AB  - Soft tissue tumors in very young children pose diagnostic and therapeutic
      challenges. Vascular tumors are the most prevalent soft tissue neoplasms in the
      neonatal period. They are generally benign tumors, but may exhibit aggressive
      behaviour and cause life-threatening complications. Fibroblastic tumors of
      intermediate prognosis, more prevalent in very young children (especially
      infantile fibrosarcoma), are locally aggressive. Since metastases are unusual in
      this group of tumors, complete surgical resection is generally curative. However,
      these tumors often present a therapeutic challenge because of the location which
      makes complete surgical resection difficult. Among the malignant soft tissue
      tumors, rhabdomyosarcoma is most frequent. It is an aggressive high-grade tumor,
      with local invasiveness and a propensity to metastasize. These tumors respond to
      chemotherapy and radiotherapy. Neonates with rhabdomyosarcoma seem to have a
      worse prognosis than in older age groups. This may be a result of inappropriate
      dosing of chemotherapeutic agents and decreased use of radiation therapy among
      other factors.

PMID- 22633290
TI  - Pediatric idiopathic intracranial hypertension and extreme childhood obesity.
AB  - OBJECTIVE: To estimate the magnitude of the association between overweight,
      moderate, and extreme childhood obesity and the risk of idiopathic intracranial
      hypertension (IIH). STUDY DESIGN: Risk estimates were obtained from the Kaiser
      Permanente Southern California Children's Health Study (n = 913 178). Weight
      classes were assigned by body mass index specific for age and sex. A combination
      of electronic database searches followed by complete medical records review was
      used to identify all children diagnosed with IIH between 2006 and 2009. RESULTS:
      We identified 78 children with IIH, the majority of whom were girls (n = 66,
      84.5%), age 11-19 (n = 66, 84.5%), non-Hispanic Whites (n = 37, 47.4%), and
      overweight or obese (n = 57, 73.1%). The adjusted ORs and 95% CIs of IIH with
      increasing weight class were 1.00, 3.56 (1.72-7.39), 6.45 (3.10-13.44), and 16.14
      (8.18-31.85) for underweight/normal weight (reference category), overweight,
      moderately obese and extremely obese 11-19 year olds, respectively (P for trend <
      .001). Other independent IIH risk factors included White non-Hispanic
      race/ethnicity for all age groups and female sex, but only in older children.
      Overweight/obese children also had more IIH symptoms at onset than normal weight
      children. CONCLUSIONS: We found that childhood obesity is strongly associated
      with an increased risk of pediatric IIH in adolescents. Our findings suggest that
      the childhood obesity epidemic is likely to lead to increased morbidity from IIH
      particularly among extremely obese, White non-Hispanic teenage girls. Our
      findings also suggest careful screening of these at risk individuals may lead to
      earlier detection and opportunity for treatment of IIH.

PMID- 22633291
TI  - Neonatal pemphigus foliaceus.

PMID- 22633292
TI  - Critical appraisal of the 'Consensus statement on care of the
      hyperglycaemic/diabetic patient during and in the immediate follow-up of an acute
      coronary syndrome'.

PMID- 22633293
TI  - Improving stress echocardiography accuracy for detecting left circumflex artery
      stenosis: a new echocardiographic sign?
AB  - BACKGROUND: The accuracy and reproducibility of stress echocardiography (SE) for
      the detection of coronary artery lesions requires improvement, particularly in
      the left circumflex artery (LCx). AIMS: To evaluate the feasibility and
      diagnostic value of a new sign: Rise of the Apical lateral wall and/or Horizontal
      displacement of the Apex toward the septum ("RA-HA") in apical echocardiographic
      views. METHODS: Consecutive patients with normal left ventricular function at
      rest, positive SE and an indication for coronary angiography were included. SEs
      were analysed blindly by three independent cardiologists: two seniors (S1 and S2)
      and one junior (J). RESULTS: Of 81 patients, 58 had an exercise SE and 23 had a
      dobutamine SE. Significant coronary stenosis was found in 59 of 77 patients who
      underwent coronary angiography (76.6%). Interobserver reproducibility for the
      presence of RA-HA was very good between S1 and S2 (kappa = 0.86), and good
      between S1 and J (0.67) and S2 and J (0.70). The sensitivity, specificity and
      positive and negative predictive values of RA-HA for the detection of significant
      coronary artery stenosis were, respectively, 39-41%, 83-89%, 88-92% and 29-31%
      for S1/S2; and 29%, 83%, 85% and 26% for J. To predict LCx stenosis (single or
      multivessel): 67-70%, 89%, 80-81% and 80-82% for S1/S2, respectively, and 50%,
      89%, 75% and 74% for J. CONCLUSION: With a short learning curve, RA-HA is easily
      diagnosed with a very good interobserver reproducibility. It has high specificity
      and PPV for the detection of a coronary artery stenosis, particularly in the LCx
      artery, during exercise or dobutamine SE.

PMID- 22633294
TI  - A single-centre experience concerning the safety of Sprint Fidelis defibrillator
      lead extraction at the time of pulse generator replacement or in case of evidence
      of lead failure.
AB  - BACKGROUND: The reported failure rate of the Sprint Fidelis defibrillator lead
      (SFDL) has increased more than initially expected, with emerging evidence of
      accelerating fracture rates. Current consensus guidelines continue to discourage
      prophylactic lead extraction, citing major complication rates of 1.4-7.3%.
      Therefore, data relating to the risks of systematic SFDL extraction are lacking,
      with no methodical extraction protocol reported to date. Moreover, few
      statistical analyses have identified predictors of SFDL failure. OBJECTIVES: The
      aims of this single-centre study were: to examine the safety and feasibility of
      systematic SFDL extraction at the time of pulse generator replacement or in case
      of lead failure; and to identify predictors of SFDL failure. METHODS: Between
      January 2005 and October 2007, 218 consecutive patients underwent transvenous
      SFDL implantation in our centre. RESULTS: During a mean follow-up of 43 +/- 15
      months, SFDL extraction was performed in 49 patients (22.5%) for the following
      reasons: inappropriate shocks (n = 21; 9.6%), systematic extraction at time of
      pulse generator extraction (n = 23; 10.5%), high impedance (n = 3; 1.4%), high
      SFDL threshold (n = 1; 0.4%) and cardiac device-related infection (n = 1; 0.4%).
      No severe complications occurred, although two minor complications were reported
      (lead dislodgments). SFDL fracture was observed in 25 patients (11.5%; 3.2%/year
      incidence). The only predictor associated with SFDL fracture was the number of
      leads (P = 0.01). CONCLUSION: In our series, SFDL extraction at the time of pulse
      generator extraction or in case of evidence of lead failure was feasible and
      safe. Number of leads was identified as a new predictive factor for SFDL
      fracture.

PMID- 22633295
TI  - Metabolic syndrome is associated with better nutritional status, but not with
      cardiovascular disease or all-cause mortality in patients on haemodialysis.
AB  - BACKGROUND: Metabolic syndrome increases the risk of cardiovascular disease (CVD)
      and all-cause mortality in the general population. AIMS: To investigate whether
      metabolic syndrome affects CVD and all-cause mortality in chronic haemodialysis
      patients. METHODS: This prospective, observational cohort study was carried out
      at Peking university third hospital from June 2006 to June 2010. Baseline
      anthropometric and laboratory parameters were evaluated, and causes and times of
      mortality were documented. Nutritional status of the patients was assessed using
      subject global assessment (SGA) and serum albumin levels. RESULTS: Of 162
      haemodialysis patients recruited, five were lost to follow-up, leaving 157 in the
      final cohort, who were followed for 36-42 months. Mean age was 62 +/- 11 years
      and 55.4% were men. Forty-six patients (30%) had metabolic syndrome. In the
      metabolic syndrome versus the non-metabolic syndrome group, there were fewer
      patients with malnutrition (by SGA) (15.2% vs. 55.0%; P < 0.001), but there were
      no significant differences in CVD mortality (8.7% vs. 10.8%; P = 0.9) or all
      cause mortality (15.2% vs. 22.5%; P = 0.39), nor in mean observed survival time
      (30.8 +/- 7.3 vs. 29.8 +/- 8.5 months; P = 0.49) or total survival time (67 +/-
      43 vs. 78 +/- 48 months; P = 0.20). Cox regression analysis showed that
      independent mortality risk factors were pre-existing CVD, age more than or equal
      to 66 years and serum albumin less than 37 g/L (indicating malnutrition).
      CONCLUSION: Metabolic syndrome was associated with a better nutritional status,
      but not with CVD or all-cause mortality in the haemodialysis patients in this
      prospective cohort study.

PMID- 22633296
TI  - Diabetic cardiomyopathy: myth or reality?
AB  - Diabetes mellitus has reached an epidemic level worldwide. Cardiovascular
      diseases are the primary cause of death in diabetic patients, not only because of
      coronary artery disease and associated hypertension but also because of a direct
      adverse effect of diabetes on the heart, independent of other potential
      aetiological factors. However, the existence of this 'diabetic cardiomyopathy'
      remains controversial. We aimed to review current evidence for the existence of
      diabetic cardiomyopathy, focusing particularly on the clinical setting.

PMID- 22633298
TI  - Cyanosis due to tricuspid regurgitation.

PMID- 22633297
TI  - Rate versus rhythm control in atrial fibrillation and clinical outcomes: updated
      systematic review and meta-analysis of randomized controlled trials.
AB  - Atrial fibrillation is the most frequently occurring sustained cardiac arrhythmia
      and is associated with a significantly increased risk of thromboembolic events
      and death. We sought to compare the clinical efficacy of rate and rhythm control
      strategies in patients with non-postoperative atrial fibrillation. We searched
      the PubMed database and the Cochrane Central Register of Controlled Trials for
      randomized controlled trials comparing rate versus rhythm control in patients
      with atrial fibrillation. Studies were retrieved and we analysed major clinical
      outcomes. Risk ratios (RRs) and 95% confidence intervals were calculated assuming
      random effects due to the clinical heterogeneity of the study populations. Eight
      randomized controlled trials were identified, with a total of 7499 patients with
      atrial fibrillation. There were no significant differences in the effects of rate
      and rhythm control on any outcome: all-cause mortality (RR: 0.95; CI: 0.86-1.05),
      cardiovascular mortality (RR: 0.99; CI: 0.87-1.13), arrhythmic/sudden death (RR:
      1.12; CI: 0.91-1.38), ischaemic stroke (RR: 0.89; CI: 0.52-1.53), systemic
      embolism (RR: 0.89; CI: 0.69-1.14) and major bleeding (RR: 1.10; CI: 0.89-1.36).
      Updated data pooled from a large population of patients with atrial fibrillation
      suggests that rate and rhythm control strategies have similar effects on major
      clinical outcomes. Other factors, including individual preferences,
      comorbidities, drug tolerance and cost issues, should be considered when choosing
      the approach for these patients.

PMID- 22633299
TI  - Right phrenic stimulation due to defibrillator implantation: a rare cause.

PMID- 22633300
TI  - Persistent anemia after implantation of the total artificial heart.
AB  - BACKGROUND: The total artificial heart (TAH) replaces the heart with 2 pneumatic
      pumps and 4 tilting disk mechanical valves. It was hypothesized that patients
      receiving TAH support have persistent hemolysis that resolves after heart
      transplantation (HT). METHODS AND RESULTS: Hematocrit (HCT) was compared in
      patients on TAH to left ventricular assist device (LVAD) support for bridge to
      HT. Data were compared with t tests. The TAH (n = 36; mean age 47 +/- 13 years)
      and LVAD patients (n = 14; mean age 53 +/- 12 years) were supported for a median
      of 83 (interquartile range [IQR] 43-115) and 106 days (IQR 84-134), respectively.
      Hematocrit was similar between the TAH and LVAD patients (34 +/- 6% vs 37 +/- 5%;
      P = .07) at baseline. After placement, TAH patients had lower HCT at 2 (20 +/- 2%
      vs 24 +/- 3%), 4 (22 +/- 3% vs 26 +/- 3%), 6 (22 +/- 4% vs 30 +/- 4%), and 8
      weeks (23 +/- 4% vs 33 +/- 5%; P < .001 for all). There were no differences in
      HCT at 1 (30 +/- 4% vs 29 +/- 7%; P = .42) and 3 months (35 +/- 7% vs 35 +/- 4%;
      P = .98) after removal of the devices for HT. TAH patients had undetectable
      haptoglobin in 96% of assessments, increased lactate dehydrogenase (1,128 +/- 384
      units/L), and detectable plasma free hemoglobin in 40% of measurements (21 +/- 15
      mg/dL). High sensitivity C-reactive protein (52 +/- 50 mg/dL) was elevated, and
      reticulocyte production index was decreased (1.6 +/- 0.6). CONCLUSIONS: Patients
      implanted with a TAH have persistent anemia that resolves only after HT. The
      association of hemolysis, ineffective erythropoiesis, and inflammation with the
      TAH warrants further study.

PMID- 22633301
TI  - Hypo- and hyperglycemia predict outcome in patients with left ventricular
      dysfunction after acute myocardial infarction: data from EPHESUS.
AB  - BACKGROUND: Hyperglycemia predicts death in cardiovascular disease, but intensive
      glucose-lowering strategies increase mortality rates in diabetes. The present
      analysis investigated the prognostic value of postadmission blood glucose (BG)
      concentration on clinical outcomes in high-risk patients with heart failure after
      acute myocardial infarction. METHODS AND RESULTS: A total of 6,496 patients from
      the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and
      Survival Study (EPHESUS) were categorized into 4 groups by plasma glucose
      concentration: <=4.5 mmol/L (hypoglycemia), 4.5-5.5 mmol/L (normoglycemia), 5.5
      8.3 mmol/L (elevated glucose level), and >8.3 mmol/L (severe hyperglycemia). We
      evaluated the time to all-cause death (primary end point) and time to
      cardiovascular death or hospitalization (secondary end point). Hypo- and severe
      hyperglycemia were prevalent in 509 (8%) and 1,588 (24%) patients, respectively.
      There was a U-shaped relationship between BG level and incidence of all-cause
      death (11.8% in patients with normoglycemia vs 15.1% and 19.9% in those with hypo
      and severe hyperglycemia; P < .001). The incidence of the secondary end point
      was increased only in hyperglycemic patients (36% vs 23% in normoglycemic
      patients; P < .001). In multivariate Cox regression analysis, hypoglycemia
      (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.06-1.81; P = .002) and
      severe hyperglycemia (HR 1.52, CI 1.27-1.83; P < .0001) proved to be strong
      predictors of all-cause death. There was no significant interaction between
      eplerenone treatment and blood glucose levels regarding clinical outcomes.
      CONCLUSIONS: In heart failure after acute myocardial infarction, both hypo- and
      hyperglycemia at the postacute phase identify patients with increased risk of
      death during long-term follow-up.

PMID- 22633302
TI  - Prospective evaluation of elastic restraint to lessen the effects of heart
      failure (PEERLESS-HF) trial.
AB  - BACKGROUND: Left ventricular (LV) remodeling predicts poor outcomes in heart
      failure (HF) patients. The HeartNet((r)) cardiac restraint device (Paracor
      Medical Inc., Sunnyvale, CA) may reduce LV remodeling and improve functional
      capacity, quality of life, and outcomes in HF patients. To evaluate the safety
      and efficacy of the HeartNet Ventricular Support System in HF patients receiving
      optimal medical therapy. METHODS AND RESULTS: Prospective, randomized,
      controlled, multicenter trial in patients with symptomatic HF and LV ejection
      fraction <=35% on optimal medical and device therapy. The primary efficacy end
      points were changes in peak VO(2), 6-minute walk (6MW) distance, and Minnesota
      Living with Heart Failure (MLWHF) quality of life score at 6 months. The primary
      safety end point was all-cause mortality at 12 months. Because the planned
      adaptive interim analysis of the first 122 subjects with a completed 6-month
      follow-up indicated futility to reach the peak VO(2) end point, trial enrollment
      was suspended. Hence, the results on the 96 treatment and 114 control subjects
      are reported. Groups were similar at baseline. At 6 months, responder frequency
      for a prespecified improvement was similar between groups for peak VO(2) (P =
      .502) and MLWHF score (P = .184) but borderline higher for improvement in 6MW
      distance in the treatment compared with the control group (33 [38%] vs. 25 [25%];
      P = .044). At 6 months, the treatment group had a significantly greater
      improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) (P < .001) and
      decrease in LV mass (P = .032), LV end-diastolic diameter (P = .015), LV end
      systolic diameter (P = .032), and LV end-diastolic volume (P = .031) as compared
      with controls. At 12 months, all-cause mortality and responder rates were similar
      in the 2 groups. Success rate for the HeartNet implantation was 99%. CONCLUSION:
      Enrollment in the trial was stopped because an interim analysis showed futility
      of reaching the peak VO(2) end point. However, because of the device safety and
      favorable signals for LV remodeling and quality of life, further investigation of
      this device is warranted.

PMID- 22633303
TI  - Prevalence, morbidity, and mortality of heart failure-related hospitalizations in
      children in the United States: a population-based study.
AB  - BACKGROUND: Few data exist on prevalence, morbidity, and mortality of pediatric
      heart failure hospitalizations. We tested the hypotheses that pediatric heart
      failure-related hospitalizations increased over time but that mortality
      decreased. Factors associated with mortality and length of stay were also
      assessed. METHODS AND RESULTS: A retrospective analysis of the Healthcare Cost
      and Utilization Project Kids' Inpatient Database was performed for pediatric (age
      <=18 years) heart failure-related hospitalizations for the years 1997, 2000,
      2003, and 2006. Hospitalizations did not significantly increase over time,
      ranging from 11,153 (95% confidence interval [CI] 8,898-13,409) in 2003 to 13,892
      (95% CI 11,528-16,256) in 2006. Hospital length of stay increased from 1997 (mean
      13.8 days, 95% CI 12.5-15.2) to 2006 (mean 19.4 days, 95% CI 18.2 to 20.6).
      Hospital mortality was 7.3% (95% CI 6.9-8.0) and did not vary significantly
      between years; however, risk-adjusted mortality was less in 2006 (odds ratio
      0.70, 95% CI 0.61 to 0.80). The greatest risk of mortality occurred with
      extracorporeal membrane oxygenation, acute renal failure, and sepsis.
      CONCLUSIONS: Heart failure-related hospitalizations occur in 11,000-14,000
      children annually in the United States, with an overall mortality of 7%. Many
      comorbid conditions influenced hospital mortality.

PMID- 22633304
TI  - Utilization of hospice and predicted mortality risk among older patients
      hospitalized with heart failure: findings from GWTG-HF.
AB  - BACKGROUND: Guidelines recommend hospice care as a treatment option for end-stage
      heart failure (HF) patients. Little is known regarding utilization of hospice
      care in a contemporary cohort of patients hospitalized with HF and how this may
      vary by estimated mortality risk. METHODS: We analyzed HF patients >=65 years (n
      = 58,330) from 214 hospitals participating in the Get With the Guidelines-HF
      program. Univariate analysis comparing patients discharged to hospice versus
      other patients was performed. Hospice utilization was evaluated for deciles of
      estimated 90-day mortality risk using a validated model. Multivariate analysis
      using admission patient and hospital characteristics was also performed to
      determine factors associated with hospice discharge. RESULTS: There were 1,442
      patients discharged to hospice, and rates of referral varied widely by hospital
      (interquartile range 0-3.7%) as shown in the univariate analysis. Patients
      discharged to hospice were significantly older and more often white, had lower
      left ventricular ejection fraction, higher B-type natriuretic peptide, and lower
      systolic blood pressure on admission. Utilization rates for each decile of 90-day
      estimated mortality risk ranged from 0.3% to 8.6%. Multivariable analysis found
      that factors associated with hospice utilization included increased age, low
      systolic blood pressure on admission, and increased blood urea nitrogen.
      CONCLUSIONS: Hospice utilization remains low among HF patients, even those with
      the highest predicted risk of death.

PMID- 22633305
TI  - Hospice care following heart failure admission: what next?

PMID- 22633306
TI  - Prognostic value of serum tenascin-C levels on long-term outcome after acute
      myocardial infarction.
AB  - BACKGROUND: Tenascin-C (TN-C), an extracellular matrix glycoprotein, is not
      normally expressed in the adult heart but transiently reappears under various
      pathologic conditions to play important roles in tissue remodeling. It is unclear
      whether serum TN-C levels add prognostic information independent from traditional
      prognostic markers. METHODS AND RESULTS: We assessed 239 patients with first ST
      segment elevation myocardial infarction who underwent successful percutaneous
      coronary intervention. We measured serum TN-C and plasma B-type natriuretic
      peptide (BNP) levels on day 5 after admission and compared long-term clinical
      outcome. During the follow-up period (24.3 +/- 13 months), 54 patients
      experienced primary composite cardiac events (cardiac death or hospitalization
      for worsening heart failure). Multivariable Cox proportional hazards analysis
      indicated that serum TN-C (hazard ratio 2.92, 95% confidence interval [CI] 1.55
      5.67; P < .001) and plasma BNP levels (hazard ratio 1.84, 95% CI 1.17-2.97; P =
      .008) were significant independent predictors for cardiac events after adjustment
      for multiple confounders. The combination of TN-C and BNP resulted in an increase
      of the c-statistic from 0.821 to 0.877 (P < .001) and an integrated
      discrimination improvement gain of 14.0% (P < .001). CONCLUSIONS: Serum TN-C
      level on day 5 after admission is potentially useful for early risk
      stratification after AMI beyond established prognostic markers.

PMID- 22633308
TI  - Markers of oxidative damage and antioxidant enzyme activities as predictors of
      morbidity and mortality in patients with chronic heart failure.
AB  - BACKGROUND: Although the majority of previous findings unequivocally confirmed
      the existence of systemic oxidative stress in chronic heart failure (CHF)
      patients, data on prognostic potential of biomarkers of oxidative lipid and
      protein damage are limited. We aimed to address the relation of oxidative stress
      markers to severity and prognosis in CHF secondary to ischemic cardiomyopathy.
      METHODS AND RESULTS: Plasma malondialdehyde (MDA), protein thiol groups (P-SH),
      reactive carbonyl derivatives (RCD), together with glutathione peroxidase (GSH
      Px) and superoxide dismutase (SOD) activities were determined in 120 CHF patients
      and 69 healthy controls. Increased lipid peroxidation (MDA) and oxidation of
      plasma proteins (RCD; P-SH) s well as downregulated GSH-Px activity were found in
      CHF patients compared with controls. Significant correlation was obtained only
      for RCD content and remodeling indices (LVEDV: r = 0.469, P = .008; LVESV: r =
      0.452; P = .011). Cox regression analysis demonstrated only MDA (HR = 3.33; CI:
      1.55-7.12; P = .002) as independent predictor of death, whereas SOD was
      associated with unstable angina pectoris (HR = 2.09; CI: 1.16-3.78; P = .011).
      CONCLUSIONS: In the course of CHF progression, carbonyl stress is implicated in
      the LV remodeling. Malondialdehyde level might be a useful parameter for
      monitoring and planning management of CHF patients.

PMID- 22633307
TI  - Changes in plasma profiles of matrix metalloproteinases (MMPs) and tissue
      inhibitors of MMPs in stress-induced cardiomyopathy.
AB  - BACKGROUND: Transient changes in the composition of the myocardial extracellular
      matrix may contribute to the ventricular systolic dysfunction in stress-induced
      cardiomyopathy (SIC). We examined the changes in plasma matrix metalloproteinases
      (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) that occur early after
      the clinical presentation of SIC. METHODS AND RESULTS: Ten patients with SIC were
      enrolled. Plasma concentrations of the 6 major MMPs (1, 2, 3, 7, 8, and 9) and
      all 4 TIMPs (1, 2, 3, and 4) were analyzed and compared with data from 15 control
      subjects. Within 24 hours of the clinical presentation, SIC patients had lower
      MMP-1 levels (0.41 +/- 0.13 vs 0.70 +/- 0.13 pg/mL; P = .048) and MMP-8 levels
      (1.61 +/- 0.34 vs 4.84 +/- 1.38 pg/mL; P = .001) and higher TIMP-4 levels (3.06
      +/- 0.40 vs 2.16 +/- 0.18 pg/mL; P = .05) compared with control. Seven of 9 SIC
      patients had elevated LV end-diastolic pressures, and all had normal LV end
      diastolic dimensions and volumes. CONCLUSIONS: Patients afflicted with SIC had
      MMP and TIMP profiles similar to those described in hypertensive heart disease
      and diastolic heart failure and different from the profiles following myocardial
      infarction. Our findings uncovered a unique biomolecular profile in SIC during
      the first 24 hours of presentation.

PMID- 22633309
TI  - Dietary omega-3 supplementation exacerbates left ventricular dysfunction in an
      ovine model of anthracycline-induced cardiotoxicity.
AB  - BACKGROUND: Cumulative dose-dependent nonischemic cardiomyopathy (NICM) remains a
      significant risk with the use of some chemotherapeutic agents. In this context,
      omega-3 polyunsaturated fatty acids (PUFA) have been investigated for their
      cardioprotective potential in rodent and in vitro models of anthracycline
      toxicity, with conflicting results. This study evaluated prophylactic omega-3
      PUFA supplementation in a large-animal model of anthracycline-induced NICM.
      METHODS AND RESULTS: Merino sheep were randomized to oral drenching with omega-3
      PUFA (fish oil; n = 8) or olive oil placebo (n = 9) 3 weeks before commencing
      repeated intracoronary infusions of doxorubicin (DOX) to induce cardiac
      dysfunction. Cumulative DOX dose was 3.6 mg/kg. Drenching was continued for 12
      weeks after final DOX exposure. Despite significant increases in tissue omega-3
      PUFA levels (P < .05 vs placebo), omega-3-treated sheep displayed greater signs
      of anthracycline cardiotoxicity than placebo animals, consisting of left
      ventricular dilatation and a greater decline in ejection fraction (P < .05),
      although myocardial fibrosis burden was similar in both groups. CONCLUSIONS:
      Dietary intake of omega-3 PUFA fails to prevent and may indeed exacerbate DOX
      induced cardiotoxicity. Clinical use of omega-3 supplementation during
      chemotherapy should be deferred until more information is available regarding the
      mechanisms of interaction between fatty acids and the myocardium during
      anthracycline exposure.

PMID- 22633310
TI  - Response to commentary by Jay Cohn, MD.

PMID- 22633312
TI  - Traumatic dissection of the vertebral artery in a toddler following a short fall.
AB  - Spontaneous subarachnoid haemorrhage (SAH) in children is uncommon, but is
      sometimes seen after rupture of aneurysms, and in different disorders. Traumatic
      SAH is common after serious accidental head injury, but is also reported after
      child abuse with vigorous shaking. To avoid unnecessary accusations of innocent
      care givers, it is important not to misinterpret the findings as abusive head
      trauma in small children with SAH. In the presented case, a nearly two-year-old
      girl was brought to the hospital after a fall witnessed by her father. The girl
      was unconscious, with elevated intracranial pressure, SAH and bilateral retinal
      haemorrhage (RH). She was pronounced dead after 9h. Premortem angiography
      revealed a dissection of the right vertebral artery, and postmortem examination
      revealed a traumatic lesion deep in the neck, at the base of the skull. Cerebral
      edema, in combination with SAH and RH, is highly suggestive of abusive head
      trauma. However, no external lesions, no skeletal lesions, especially no long
      bone metaphyseal lesions, or subdural haematomas occurring at the same time as
      SAH, were found. There was no report of previous child abuse in the family. Based
      on the radiological and postmortem findings, we believe that an accidental fall
      caused a blunt force trauma with a subsequent dissection of the right vertebral
      artery. To our knowledge, accidental tear of one of the vertebral arteries,
      leading to SAH in a toddler, has previously not been described. Child abuse is an
      important exclusion diagnosis with serious legal implications.

PMID- 22633313
TI  - [Clinical and therapeutic aspects in Tunisian patients with dystonia: a 5-year
      prospective study].
AB  - INTRODUCTION: Studies of dystonia are heterogeneous and there are no studies on
      this disease in Tunisia. The aim of our study was to determine the frequency of
      dystonia in the hospital population, to identify different forms of dystonia
      according to age of onset, distribution, to determine etiologies and to describe
      treatment. METHODS: We conducted a prospective study over a 5-year period (from
      January 2005 to November 2009) including all patients diagnosed with dystonia and
      followed at the Child and Adolescent Neurology Department and "Movement Disorders
      and Botulinum Toxin" consultation of the National Institute of Neurology of
      Tunis. RESULTS: Two hundred patients were included (2.2% of our patients). Mean
      age was 26.4+/-21.4 years and sex ratio H:F 1.3. Consanguinity rate was 29%. Main
      features of dystonia were action dystonia (78.5%), generalized forms (47%) and
      secondary forms (58%). A pyramidal syndrome and other movement disorders were the
      most common signs associated with dystonia (36.5% and 33.5% respectively). In the
      group of secondary dystonia, mains etiologies were dystonia due to exogenic agent
      (56%), neuro-metabolic diseases (26%), hereditary degenerative disease (13%) and
      psychogenic dystonia (5%). Dystonia was primary in 44% (84 patients). Different
      treatments were used and a dramatic improvement in some patients was noted with
      levodopa and botulinum toxin injections. A multidisciplinary approach associated
      with medical treatment led to recovery or improved prognosis. DISCUSSION AND
      CONCLUSION: Very few studies have been devoted to reporting a large series of
      dystonic patients. Our study is the first to describe both primary and secondary
      dystonia in 200 Tunisian patients. The presence of familial dystonia in our
      country suggests a genetic origin. Further work including genetic analysis with a
      screening of known mutations responsible for dystonia and the informative
      families with unknown mutations would be useful. Specific studies designed to
      identify new genes causal in dystonia are needed.

PMID- 22633314
TI  - [Acute stroke: new recommendations again?].

PMID- 22633315
TI  - Universities' expectations of pastoral care: trends, stressors, resource gaps and
      support needs for teaching staff.
AB  - OVERVIEW: Since the mid-90s, the university environment has challenged the
      motivation of academic staff to engage in pastoral care. A literature review
      revealed five themes that aligned with analysis of interview data from a previous
      study (Laws and Fiedler, 2010). The key themes were i) staff were often disturbed
      by unplanned intrusions of students who exhibited behavioural problems or sought
      emotional support, ii) the management of emotions in face-to-face encounters was
      stressful, iii) staff felt under-equipped for dealing with Mental Health (MH)
      issues, iv) standards and control needed updating and v) counselling and
      disability services did not meet academics' need to know about 'at risk'
      students. OBJECTIVE: Having identified the incidence of mental health issues
      among Australian University students, this study aims to locate literature that
      describes how well current university policies/protocols are supported by
      Evidence Based Practice in the management of MH problems in the student
      population. DESIGN/SETTING/PARTICIPANTS: Findings from a content analysis of the
      literature were triangulated with verbatim comments recorded during a previous
      study that utilised semi structured interviews with 34 academics at the School of
      Nursing and Midwifery and the School of Commerce at the University of South
      Australia (Laws and Fiedler, 2010). RESULTS: Lack of clarity on role boundaries
      around promotion of students' well-being was not clearly defined. The Higher
      Education (HE) institutions' slowness in responding to mental health needs of
      students combined with the increasing expectations of academics' performance
      monitoring has lead staff to avoid deep investment in their students' well-being.
      The literature indicates that students are in need of psychological support, but
      pastoral care remains ill-defined despite enduring expectations held by
      university administrators. Teacher motivation is diminished by time spent with
      students in need of emotional support which is not acknowledged in workloads.
      Staff stress is increased by 'emotion work' requiring a greater integration of
      resources that guide them toward more appropriate and timely student support.
      CONCLUSION: Staff require ongoing professional development on the nature of MH
      problems among students. There is a need for specific orientation programs that
      better define pastoral care and identify support services for staff and students.
      Universities need to focus on what is needed to create a well-being environment.
      Workload allocations must include 'emotion work', and mental health professionals
      must be employed to improve intervention and support not only for students but
      also for University staff. With better defined pastoral care roles, academics can
      more effectively balance their intrinsic and extrinsic motivations toward both
      personal and corporate objectives. Further research into the efficacy of
      university resourcing of programs and services is needed.

PMID- 22633316
TI  - Static posturography with dynamic tests. Usefulness of biomechanical parameters
      in assessing vestibular patients.
AB  - INTRODUCTION AND OBJECTIVE: Posturography allows evaluating postural control.
      This study showed the posturographic parameters that were useful for assessing
      the functional ability to maintain balance in our sample of vestibular patients.
      MATERIAL AND METHODS: Of a total of 89 patients, 59 were healthy subjects and 30
      had a peripheral vestibular disorder. The subjects were studied using the
      posturographic NedSVE/IBV system, combining static (Romberg) and dynamic
      (stability limits and rhythmic weight shifts) tests. We then compared the
      measurements found in the groups. RESULTS: Normal subjects showed significantly
      lower oscillations than our patients in all of the posturographic parameters
      studied (except the displacement angle). In testing the limits of stability,
      although normal subjects achieved maximum displacements greater than the subjects
      with the disorder, the differences found were not significant. In rhythmic weight
      shift tests, normal subjects showed more favourable results than did the
      vestibular patients, with significant differences in 3 of the 4 parameters
      studied: 1) anteroposterior ability, 2) mediolateral ability, and 3)
      anteroposterior control and efficiency. CONCLUSION: Rhythmic weight shift tests
      and the static posturography test parameters used were useful in discriminating
      among the normal and pathological subjects in this study.

PMID- 22633317
TI  - Prostate-specific antigen kinetics and outcomes in patients with bone metastases
      from castration-resistant prostate cancer treated with or without zoledronic
      acid.
AB  - BACKGROUND: Zoledronic acid (ZOL) is a standard therapy for the prevention of
      skeletal-related events (SREs) in patients with castration-resistant prostate
      cancer (CRPC). Although prostate-specific antigen (PSA) is an established marker
      for monitoring prostate cancer patients, correlations between PSA and disease
      outcomes during ZOL therapy are unclear. OBJECTIVE: To evaluate the relationships
      among PSA kinetics, bone-directed therapy with ZOL, and clinical outcomes in men
      with bone metastases from CRPC using a ZOL phase 3 trial database. DESIGN,
      SETTING, AND PARTICIPANTS: Exploratory analyses from a phase 3 trial in men with
      bone metastases from CRPC (n=643) randomized to ZOL or placebo every 3 wk.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels during the first 3 mo
      of the study were evaluated in linear and logarithmic (log) models stratified
      using prognostic factors established in a ZOL phase 3 trial and a CRPC nomogram.
      Relative risks of SREs, bone disease progression (BDP), and death were calculated
      per 1 log (nanograms per milliliter) PSA increase. Baseline PSA models used the
      study median (PSA: 77.3 ng/ml) as the high/low cut-off point. RESULTS AND
      LIMITATIONS: A total of 202 placebo- and 434 ZOL-treated patients were
      assessable. In both groups, PSA increases correlated with significantly increased
      risks of death, BDP, and first SRE. In the placebo and ZOL groups, associated
      increases in risk per 1 log (nanograms per milliliter) PSA increase were 29%
      (p<0.0001) and 10% (p<0.0074), respectively, for BDP, and 24% (p=0.0010) and 13%
      (p=0.0079), respectively, for first SRE. Limitations include the retrospective
      nature of these analyses and the potential confounding effects of concurrent
      antineoplastic therapies. CONCLUSIONS: PSA is an important prognostic tool for
      survival in patients with bone metastases from CRPC, and these analyses show that
      PSA is also prognostic for BDP and SREs regardless of bone-targeted therapy.

PMID- 22633318
TI  - Rationale for percutaneous biopsy and histologic characterisation of renal
      tumours.
AB  - CONTEXT: The use of percutaneous biopsy of renal tumours has been traditionally
      reserved for selected cases because of uncertainties regarding its safety,
      accuracy, and clinical utility. With the adoption of modern biopsy techniques and
      increasing expertise in interpreting biopsy specimens, renal tumour biopsy today
      has limited morbidity and allows histologic diagnosis in the majority of cases in
      centres with expertise. OBJECTIVE: To review the current rationale, indications,
      and outcomes of percutaneous biopsies and histologic characterisation of renal
      tumours. EVIDENCE ACQUISITION: We conducted a systematic review of English
      language articles on percutaneous biopsies of renal tumours published between
      January 1999 and December 2011 using the Medline, Embase, and Web of Science
      databases. One hundred twelve articles were selected with the consensus of all
      authors and analysed according to the Preferred Reporting Items for Systematic
      Reviews and Meta-analysis (PRISMA) criteria. EVIDENCE SYNTHESIS: In recent years,
      the increasing incidence of incidental small renal masses (SRMs), the development
      of conservative and minimally invasive treatments for low-risk renal cell
      carcinoma (RCC), and the discovery of novel targeted treatments for metastatic
      disease have provided the rationale for expanding the indications for renal
      tumour biopsy. Percutaneous biopsy for diagnostic assessment of SRMs can avoid
      unnecessary surgeries and support treatment decisions, especially in patients at
      high surgical risk. Biopsies can confirm histologic success after thermal
      ablation of SRMs and support the selection of the appropriate systemic therapy
      for metastatic RCC. There is increasing evidence that further diagnostic and
      prognostic information can be obtained from renal tumour biopsies with the use of
      immunohistochemistry, cytogenetic and molecular analysis, and high-throughput
      gene expression profiling. CONCLUSIONS: Percutaneous biopsies have increasing
      indications and can significantly contribute to clinical management of renal
      tumours but are still underutilised in clinical practice. Further research is
      needed to define optimal and standardised patterns of biopsy and improve the
      accuracy of biopsies to determine tumour histology. Molecular and genetic
      analysis of biopsy specimens can provide additional information to support
      patient counselling and treatment decision making.

PMID- 22633320
TI  - Basophil activation test and autologous serum skin test: not overlapping tests in
      chronic urticaria.

PMID- 22633321
TI  - Comparable IgE reactivity to natural and recombinant Api m 1 in cross-reactive
      carbohydrate determinant-negative patients with bee venom allergy.

PMID- 22633322
TI  - Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: implications for
      the development of vaccines against helminths.
AB  - BACKGROUND: Necator americanus Ancylostoma-secreted protein 2 (Na-ASP-2) is
      secreted by infective hookworm larvae on entry into human hosts. Vaccination of
      laboratory animals with recombinant Na-ASP-2 provides significant protection
      against challenge infections. In endemic areas antibodies to Na-ASP-2 are
      associated with reduced risk of heavy N americanus infections. OBJECTIVE: To
      assess the safety and immunogenicity of recombinant Na-ASP-2 adjuvanted with
      Alhydrogel in healthy Brazilian adults previously infected with N americanus.
      METHODS: Participants were randomized to receive Na-ASP-2 or hepatitis B vaccine.
      Major IgG and IgE epitopes of the Na-ASP-2 molecule were mapped by using sera
      from these same subjects. Seroepidemiologic studies in adults and children
      residing in hookworm-endemic areas were conducted to assess the prevalence of IgE
      responses to Na-ASP-2. RESULTS: Vaccination with a single dose of Na-ASP-2
      resulted in generalized urticarial reactions in several volunteers. These
      reactions were associated with pre-existing Na-ASP-2-specific IgE likely induced
      by previous hookworm infection. Surveys revealed that a significant proportion of
      the population in hookworm-endemic areas had increased levels of IgE to Na-ASP-2.
      Epitope mapping demonstrated sites on the Na-ASP-2 molecule that are uniquely or
      jointly recognized by IgG and IgE antibodies. CONCLUSION: Infection with N
      americanus induces increased levels of total and specific IgE to Na-ASP-2 that
      result in generalized urticaria on vaccination with recombinant Na-ASP-2. These
      data advance knowledge of vaccine development for helminths given their
      propensity to induce strong T(H)2 responses. Study data highlight the important
      differences between the immune responses to natural helminth infection and to
      vaccination with a recombinant helminth antigen.

PMID- 22633325
TI  - Fungal and atopic sensitization are low among farmers in the Agricultural Health
      Study.

PMID- 22633326
TI  - Possible roles of 2 basidiomycetous fungi in allergic fungal respiratory disease.

PMID- 22633327
TI  - Population-based study of multiplexed IgE sensitization in relation to asthma,
      exhaled nitric oxide, and bronchial responsiveness.
AB  - BACKGROUND: IgE sensitization is an important risk factor for the development of
      asthma. OBJECTIVE: The aim of this study was to investigate the IgE antibody
      profile for a broad spectrum of allergen molecules in asthmatic patients.
      METHODS: Participants from the European Community Respiratory Health Survey II
      (n=467) were tested with ImmunoCAP ISAC against 103 allergen molecules. The
      presence of bronchial hyperresponsiveness was measured with a methacholine
      challenge test and bronchial inflammation with fraction of exhaled nitric oxide
      (Feno). RESULTS: A total of 38% of the controls and 72% of the asthmatic patients
      were sensitized against at least 1 of the allergen components (P<.0001). Asthma
      was independently related to having IgE antibodies against pollen (odds
      ratio=2.2) and perennial airway allergens (odds ratio=5.6), increased Feno was
      independently related to having IgE antibodies against food allergens and
      perennial allergens, while bronchial responsiveness was independently associated
      with having IgE antibodies against only perennial allergens. Sensitization to
      food allergens was related to asthma and increased Feno if IgE antibody against
      pollen allergens was present. Simultaneous sensitization to perennial, pollen,
      and food allergens involves the highest risk of asthma (odds ratio=18.3),
      bronchial inflammation, and responsiveness. CONCLUSIONS: Feno, bronchial
      responsiveness, and the risk of asthma increase with multiple sensitizations to
      different allergen groups. We show for the first time that the presence of IgE
      antibodies against food allergens is independently associated with increased Feno
      and increases the risk of asthma in subjects with simultaneous sensitization to
      pollen allergens.

PMID- 22633328
TI  - Airway epithelial cells activate TH2 cytokine production in mast cells through IL
      1 and thymic stromal lymphopoietin.
AB  - BACKGROUND: Airway epithelial cells are important regulators of innate and
      adaptive immunity. Although mast cells are known to play a central role in
      manifestations of allergic inflammation and are found in the epithelium in
      patients with T(H)2-related diseases, their role is incompletely understood.
      OBJECTIVES: The objective of this study was to investigate the role of airway
      epithelial cells in the production of T(H)2 cytokines in mast cells. METHODS:
      Normal human bronchial epithelial (NHBE) cells were stimulated with TNF, IL-4,
      IFN-gamma, IL-17A, and double-stranded RNA (dsRNA) alone or in combination. Human
      mast cells were stimulated with epithelial cell-derived supernatants or
      cocultured with NHBE cells. T(H)2 cytokine responses were blocked with
      neutralizing antibodies. RESULTS: Supernatants from IL-4- and dsRNA-stimulated
      NHBE cells significantly enhanced T(H)2 cytokine production from mast cells. The
      combination of IL-4 and dsRNA itself or supernatants from NHBE cells stimulated
      with other cytokines did not activate mast cells, suggesting that mast cell
      responses were induced by epithelial cell factors that were only induced by IL-4
      and dsRNA. Epithelial supernatant-dependent T(H)2 cytokine production in mast
      cells was suppressed by anti-IL-1 and anti- thymic stromal lymphopoietin (TSLP)
      and was enhanced by anti-IL-1 receptor antagonist. Similar results were observed
      in coculture experiments. Finally, we found dsRNA-dependent production of IL-1,
      TSLP, and IL-1 receptor antagonist in NHBE cells was regulated by T(H) cytokines,
      and their ratio in NHBE cells correlated with T(H)2 cytokine production in mast
      cells. CONCLUSIONS: Pathogens producing dsRNA, such as respiratory viral
      infections, might amplify local T(H)2 inflammation in asthmatic patients through
      the production of TSLP and IL-1 by epithelial cells and subsequent activation of
      T(H)2 cytokine production by mast cells in the airways.

PMID- 22633329
TI  - Vibratory and perceptual measurement of resonant voice.
AB  - PURPOSE: This study set out to investigate whether there existed a correlation
      between auditory-perceptual judgment of resonant voice and the physical vibration
      in the facial bone. The magnitude of bone vibration in the facial bone during
      different types of voice production (resonant vs nonresonant vs strained voices)
      was also investigated. METHOD: Thirty-six healthy normal subjects produced three
      types of phonations: resonant voice, habitual nonresonant voice, and strained
      voice. A piezoelectric accelerometer was used to measure the vibrations in the
      nasal bridge and the perilaryngeal area during the phonation. Seventy-two
      selected nasal sounds (/ma/) produced under the resonant voice condition by these
      speakers were rated by two experienced speech pathologists on the magnitude of
      auditory-perceptual resonance using an 11-point equal-appearing interval scale.
      The magnitude of bone vibration was also compared across the three voice types.
      RESULTS: Significant moderate correlations were found between the physical bone
      vibration and the auditory-perceptual rating of resonant voice at the nasal
      bridge of the facial bone (0.6). Resonant voice, compared with the strained and
      nonresonant voice types, was also found to have a significant increase in the
      magnitude of facial bone vibration. Nasal stimuli, compared with nonnasal
      stimuli, facilitated greater bone vibration during resonant voice production.
      CONCLUSION: Piezoelectric accelerometer, as an objective quantitative tool,
      measures reliably the extent of bone vibration in resonant voice phonation. It is
      a useful tool for determining the bone vibration in relation to resonant voice.

PMID- 22633330
TI  - Influence of vowel selection on determination of phonation threshold pressure.
AB  - OBJECTIVE/HYPOTHESIS: Phonation threshold pressure values reported in the
      literature have largely been determined with use of one of three consonant-vowel
      sequences, /pi/, /pae/, and /pa/; however, it is not currently known if vowel
      choice influences phonation threshold pressure values. Based on the evidence that
      describes velopharyngeal closure variations between vowels, this research effort
      hypothesized that phonation threshold pressure values measured from the consonant
      vowel sequence /pi/ would be significantly lower than the /pae/ and /pa/
      sequences. METHODS: Twelve female participants aged between 20 and 27 years
      produced five-syllable trains of /pi/, /pae/, and /pa/ at low, modal, and high
      pitches. STUDY DESIGN: A within-subject repeated measures approach was conducted
      to compare phonation threshold pressure value differences between the three
      consonant-vowel sequences for three different pitches while controlling for other
      task elicitation variables that may also influence phonation threshold pressure
      values. RESULTS: Repeated measures analysis of the data indicated that there was
      no significant difference (P<0.05) in phonation threshold pressure values between
      the three consonant-vowel sequences at any frequency assessed. Further, for all
      three consonant-vowel sequences measured, significant differences of phonation
      threshold pressure magnitude were observed when comparing the high frequency
      versus the low and modal frequencies, a finding consistent with previous
      publications. CONCLUSIONS: The vowel selected for task elicitation for phonation
      threshold pressure determination does not appear to significantly affect
      phonation threshold values, indicating flexibility of the vowel aspect of this
      measure for clinical use of phonation threshold pressure.

PMID- 22633331
TI  - Managing voice impairment after injection laryngoplasty.
AB  - To date, there is a paucity of literature on the management of suboptimal voice
      outcomes after injection laryngoplasty. We present three cases of worsened voice
      quality and impaired mucosal waveform propagation on videostroboscopy after
      calcium hydroxylapatite (CaHA) injection. The first was found to have superficial
      deposits of CaHA in Reinke's space. The second case appeared to have
      overaugmentation of the vocal folds. The third case had atrophic vocal folds, and
      despite having a deep CaHA injection (within the thyroarytenoid muscles), the
      injected vocal folds had diminished mucosal waveform amplitude, which was likely
      because of poor pulmonary function. In summary, there can be multiple reasons for
      suboptimal voice outcomes after CaHA. Clinician awareness and intraoperative
      recognition of improper CaHA injection/overinjection can help prevent most
      negative outcomes.

PMID- 22633332
TI  - Histological organization is similar in human vocal muscle and tongue--a study of
      muscles and nerves.
AB  - One of the most exciting questions about the human voice is how the vocal fold
      produces and modulates different sounds. One hypothesis to explain the wide range
      of movements found in the vocal fold is based on the variety of muscle fiber
      orientations in the thyroarytenoid (TA) muscle. The tongue (TO) muscle is
      considered the most complex structure in the body in terms of muscle fiber
      orientation and movements. Thus, possible similarities between these two muscles
      and their innervations, the recurrent laryngeal nerve (RLN) and hypoglossal nerve
      (XII), could explain the complex movements executed by the focal fold. Moreover,
      such studies help us to understand some microanatomical aspects of vocal fold
      reinnervation, based on XII-to-RLN anastomosis. Therefore, this study
      investigates the histological organization of TA and TO muscles and their
      innervations (n=12 subjects). The muscle fibers were classified into three
      categories according to their orientation (transverse, undefined, and
      longitudinal). To quantify the percentage of fibers in each category in the TA
      and TO, the shape coefficient (shape Z) was estimated. Qualitative analysis and
      estimation of fiber area and shape Z show that the histological organization of
      TA and TO muscle is similar. Both muscles present the same percentage of
      transversal (~72%), undefined (~15%), and longitudinal fibers (~10%). By
      contrast, the authors' analysis of the morphometric parameters of the RLN and XII
      shows that there is no correlation between these nerves. In conclusion, in
      humans, TA and TO muscles present similar histological organization and this
      finding could help to explain interesting questions about human phonation.

PMID- 22633333
TI  - Perturbation of voice signals in register transitions on sustained frequency in
      professional tenors.
AB  - PURPOSE: Vocal register transitions in the passaggio region remain an unclarified
      field in classically trained male singers. METHOD: We examined the acoustic and
      electroglottographic signals of seven tenors' transitions from voix mixte to
      falsetto on a sustained pitch F4 (349Hz) on the vowels /a, e, i, o, u, and ae/.
      RESULTS: It was found that in many of the tested subjects, register transitions
      between voix mixte and falsetto were performed very continuously without clear
      register transition events. However, an increase of frequency and amplitude
      perturbation (jitter, relative average perturbation, and shimmer) was observed
      during register transitions. CONCLUSION: These data suggest that professional
      tenors are able to avoid sudden registration events frequently observed in
      untrained voices.

PMID- 22633334
TI  - Vocal fold vibratory characteristics of healthy geriatric females--analysis of
      high-speed digital images.
AB  - OBJECTIVES/HYPOTHESIS: A high proportion of the geriatric population suffers from
      presbylaryngis and presbyphonia; however, our knowledge of vibratory patterns in
      this population is almost nonexistent. In this study, we investigate the vocal
      fold vibratory patterns of healthy elderly females to determine which features or
      combination of them could best describe the geriatric voices. STUDY DESIGN: Cross
      sectional study with 20 elderly healthy females with no history of voice
      problems. METHODS: Hilbert transformed glottal area waveforms (GAWs) from serial
      high-speed digital imaging of sustained phonation are used to provide
      quantitative measures of glottal vibratory characteristics and perturbations;
      open quotient, jitter, and shimmer. Nyquist plots provide interpretable patterns
      to portray the vibratory characteristics as clear, pressed, breathy, and atypical
      patterns. RESULTS: The GAW from most elderly speakers (50%) showed vibratory
      characteristics associated with a more pressed voice and higher glottal
      perturbation values: their Nyquist plot patterns show wide scatterings around the
      rim of the plot reflecting a much-reduced ability in sustaining vibratory
      oscillation; these were distinct differences from previously reported data on
      younger speakers. Qualitative examination revealed more anteriorly placed glottal
      gaps in the geriatric females. CONCLUSION: These findings have important
      implications in understanding voice production in the geriatric population and in
      helping to establish normal perturbation references among female speakers across
      age.

PMID- 22633335
TI  - High prevalence of acquired quinolone-resistance genes among Enterobacteriaceae
      from Saudi Arabia with CTX-M-15 beta-lactamase.
AB  - We examined the prevalence of acquired quinolone resistance determinants among
      Enterobacteriaceae with extended-spectrum beta-lactamases (ESBLs) in Riyadh,
      Saudi Arabia. qnrA, qnrB, qnrS, aac(6')-Ib-cr, and qepA genes were sought by
      polymerase chain reaction (PCR) in 160 nonduplicate, clinical Enterobacteriaceae
      with ESBLs from Prince Salman Hospital in Riyadh during 2009. MICs were
      determined for qnr- and aac(6')-Ib-cr-positive isolates. Mutations in gyrA and
      parC were determined for isolates with qnr. ESBL genes were characterized by PCR
      and sequencing. Among 99 ESBL-producing Escherichia coli, 73% were ciprofloxacin
      resistant, as were 74% of 61 ESBL-positive Klebsiella pneumoniae. The aac(6')-1b
      cr gene was present in 76 ESBL producers, comprising 34 K. pneumoniae and 42 E.
      coli, whereas qnrA or qnrB genes were found in 21 isolates, all of them also
      harbouring aac(6')-1b-cr and bla(CTX-M-15), with the latter encoding what was
      considerably the dominant ESBL in the collection. The qnr-positive isolates
      harboured a variety of mutation in gyrA and parC but, even with aac(6')-1b-cr
      also present, high-level ciprofloxacin resistance (MIC >32 MUg/mL) was invariably
      associated with double mutations in gyrA, affecting both Ser83 and Asp87 along
      with >1 substitution in parC, affecting Ser80 or Glu84.

PMID- 22633336
TI  - Rapid identification of microorganisms isolated from throat swab specimens of
      community-acquired pneumonia patients by two MALDI-TOF MS systems.
AB  - The rapid and reliable identification of pathogens is crucial for confirming
      infections concomitant with community-acquired pneumonia (CAP), guiding
      antimicrobial therapy, and epidemiologic surveillance. In this study, 2 matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) systems coupled to the Biotyper or SARAMIS database were used to identify
      strains isolated from the throat swab samples of 70 CAP patients. The analysis of
      16S rRNA gene sequencing was used as the reference method. A total of 212
      suspicious colonies representing 12 genera and 30 species were identified. Of
      these, 99.1% (total 210/212 and 202/212 in Biotyper and 193/212 in SARAMIS) were
      successfully identified with 93.4% (total 198 /212 and 190/212 in Biotyper and
      149/212 in SARAMIS) identified at the species level. The integrity and
      comprehensiveness of the databases are the main reason for the significant
      differences in the identification of isolates between the Biotyper and SARAMIS
      systems. As a rapid, economical, and high-throughput method, MALDI-TOF MS is an
      effective alternative identification method that can aid in the diagnosis and
      surveillance of CAP.

PMID- 22633337
TI  - Fatal bronchial invasion of Scopulariopsis brevicaulis in an acute monocytic
      leukemia patient.
AB  - A case of fatal invasion of Scopulariopsis brevicaulis to the bronchus in an
      acute monocytic leukemia (M(5)) patient is described. This infection leads to
      mediastinal emphysema, bronchial bleeding, and bronchial obstruction before
      finally spreading to the entire lung. The patient was initially diagnosed with
      pulmonary aspergillosis based on clinical signs and morphological examination.
      However, S. brevicaulis was finally identified by 18S rDNA sequencing. The
      patient failed lipid amphotericin B therapy and voriconazole plus caspofungin
      combination therapy. To the best of our knowledge, this is the first report on S.
      brevicaulis affecting the bronchus and resulting in a fatal prognosis in an M(5)
      patient.

PMID- 22633338
TI  - Emergency department discharge prescription interventions by emergency medicine
      pharmacists.
AB  - STUDY OBJECTIVE: We determine the rate and details of interventions associated
      with emergency medicine pharmacist review of discharge prescriptions for patients
      discharged from the emergency department (ED). Additionally, we evaluate care
      providers' satisfaction with such services provided by emergency medicine
      pharmacists. METHODS: This was a prospective observational study in the ED of an
      academic medical center that serves both adult and pediatric patients. Details of
      emergency medicine pharmacist interventions on discharge prescriptions were
      compiled with a standardized form. Interventions were categorized as error
      prevention or optimization of therapy. The staff of the ED was surveyed related
      to the influence and satisfaction of this new emergency medicine pharmacist
      provided service. RESULTS: The 674 discharge prescriptions reviewed by emergency
      medicine pharmacists during the study period included 602 (89.3%) for adult
      patients and 72 (10.7%) for pediatric patients. Emergency medicine pharmacists
      intervened on 68 prescriptions, resulting in an intervention rate of 10.1% (95%
      confidence interval [CI] 8.0% to 12.7%). The intervention rate was 8.5% (95% CI
      6.4% to 11.1%) for adult prescriptions and 23.6% for pediatric prescriptions (95%
      CI 14.7% to 35.3%) (difference 15.1%; 95% CI 5.1% to 25.2%). There were a similar
      number of interventions categorized as error prevention and optimization of
      medication therapy, 37 (54%) and 31 (46%), respectively. More than 95% of survey
      respondents believed that the new pharmacist services improved patient safety,
      optimized medication regimens, and improved patient satisfaction. CONCLUSION:
      Emergency medicine pharmacist review of discharge prescriptions for discharged ED
      patients has the potential to significantly improve patient care associated with
      suboptimal prescriptions and is highly valued by ED care providers.

PMID- 22633339
TI  - Evaluating age in the field triage of injured persons.
AB  - STUDY OBJECTIVE: We evaluate trauma undertriage by age group, the association
      between age and serious injury after accounting for other field triage criteria
      and confounders, and the potential effect of a mandatory age triage criterion for
      field triage. METHODS: This was a retrospective cohort study of injured children
      and adults transported by 48 emergency medical services (EMS) agencies to 105
      hospitals in 6 regions of the western United States from 2006 through 2008. We
      used probabilistic linkage to match EMS records to hospital records, including
      trauma registries, state discharge databases, and emergency department databases.
      The primary outcome measure was serious injury, as measured by an Injury Severity
      Score greater than or equal to 16. We assessed undertriage (Injury Severity Score
      >=16 and triage-negative or transport to a nontrauma center) by age decile and
      used multivariable logistic regression models to estimate the association (linear
      and nonlinear) between age and Injury Severity Score greater than or equal to 16,
      adjusted for important confounders. We also evaluated the potential influence of
      age on triage efficiency and trauma center volume. RESULTS: Injured patients
      (260,027) were evaluated and transported by EMS during the 3-year study period.
      Undertriage increased for patients older than 60 years, reaching approximately
      60% for those older than 90 years. There was a strong nonlinear association
      between age and Injury Severity Score greater than or equal to 16. For patients
      not meeting other triage criteria, the probability of serious injury was most
      notable after 60 years. A mandatory age triage criterion would have decreased
      undertriage at the expense of overtriage, with 1 patient with Injury Severity
      Score greater than or equal to 16 identified for every 60 to 65 additional
      patients transported to major trauma centers. CONCLUSION: Trauma undertriage
      increases in patients older than 60 years. Although the probability of serious
      injury increases among triage-negative patients with increasing age, the use of a
      mandatory age triage criterion appears inefficient for improving field triage.

PMID- 22633340
TI  - A model of cost-effectiveness of tissue plasminogen activator in patient
      subgroups 3 to 4.5 hours after onset of acute ischemic stroke.
AB  - STUDY OBJECTIVE: The European Cooperative Acute Stroke Study III (ECASS III)
      showed that recombinant tissue plasminogen activator (rtPA) administered 3 to 4.5
      hours after acute ischemic stroke led to improvement in patient disability versus
      placebo. We evaluate the long-term incremental cost-effectiveness of rtPA
      administered 3 to 4.5 hours after acute ischemic stroke onset versus no treatment
      according to patient clinical and demographic factors. METHODS: We developed a
      disease-based decision analytic model to project lifetime outcomes of patients
      post-acute ischemic stroke from the payer perspective. Clinical data were derived
      from the ECASS III trial, longitudinal cohort studies, and health state
      preference studies. Cost data were based on Medicare reimbursement and other
      published sources. We performed probabilistic sensitivity analyses to evaluate
      uncertainty in the analysis. RESULTS: rtPA in a hypothetical cohort resulted in a
      gain of 0.07 years of life (95% credible range 0.0005 to 0.17) and 0.24 quality
      adjusted life-years (95% credible range 0.01 to 0.60) and a difference in cost of
      $1,495 (95% credible range -$4,637 to $6,100) compared with placebo. The
      incremental cost-effectiveness ratio for all patients was $6,255 per quality
      adjusted life-year gained; for patients younger than 65 years, cost saving; for
      patients aged 65 years or older, $35,813 per quality-adjusted life-year; for
      patients with baseline National Institutes of Health Stroke Scale (NIHSS) score 0
      to 9, $16,322 per quality-adjusted life-year; for patients with NIHSS score 10 to
      19, $37,462 per quality-adjusted life-year; and for patients with NIHSS score
      greater than or equal to 20, $2,432 per quality-adjusted life-year. The majority
      of other subgroups such as sex, history of stroke, and history of hypertension
      were either cost saving or cost-effective, with the exceptions of diabetes and
      atrial fibrillation. CONCLUSION: The results indicate that rtPA in the 3- to 4.5
      hour therapeutic window provides improvement in long-term patient outcomes in
      most patient subgroups and is a good economic value versus no treatment.

PMID- 22633341
TI  - Distribution of specialized care centers in the United States.
AB  - STUDY OBJECTIVE: As a recommended strategy for optimally managing critical
      illness, regionalization of care involves matching the needs of the target
      population with available hospital resources. The national supply and
      characteristics of hospitals providing specialized critical care services is
      currently unknown. We seek to characterize the current distribution of
      specialized care centers in the United States. METHODS: Using public data linked
      with the American Hospital Association directory and US Census, we identified US
      general acute hospitals providing specialized care for ST-segment elevation
      myocardial infarction (STEMI) (>=40 annual primary percutaneous coronary
      interventions reported in Medicare Hospital Compare), stroke (The Joint
      Commission certified stroke centers), trauma (American College of Surgeons or
      state-designated, adult or pediatric, level I or II), and pediatric critical care
      (presence of a pediatric ICU) services. We determined the characteristics and
      state-level distribution and density of specialized care centers (centers per
      state and centers per state population). RESULTS: Among 4,931 acute care
      hospitals in the United States, 1,325 (26.9%) provided one of the 4 defined
      specialized care services, including 574 STEMI, 763 stroke, 508 trauma, and 457
      pediatric critical care centers. Approximately half of the 1,325 hospitals
      provided 2 or more specialized services, and one fifth provided 3 or 4
      specialized services. There was variation in the number of each type of
      specialized care center in each state: STEMI median 7 interquartile range (IQR 2
      to 14), stroke 8 (IQR 3 to 17), trauma 6 (IQR 3 to 11), pediatric specialized
      care 6 (IQR 3 to 11). Similarly, there was variation in the number of each type
      of specialized care center per population: STEMI median 1 center per 585,135
      persons (IQR 418,729 to 696,143), stroke 1 center per 412,188 persons (IQR
      321,604 to 572,387), trauma 1 center per 610,589 persons (IQR 406,192 to
      917,588), and pediatric critical care 1 center per 665,282 persons (IQR 441,525
      to 942,254). The national distribution patterns differed for each type of
      specialized care center. CONCLUSION: The distribution of specialized care centers
      varies across the United States. These observations highlight unanswered
      questions about the regional organization of specialized care in the United
      States.

PMID- 22633342
TI  - Effect of bedside ultrasonography on the certainty of physician clinical
      decisionmaking for septic patients in the emergency department.
AB  - STUDY OBJECTIVE: Sepsis protocols promote aggressive patient management,
      including invasive procedures. After the provision of point-of-care
      ultrasonographic markers of volume status and cardiac function, we seek to
      evaluate changes in emergency physician clinical decisionmaking and physician
      assessments about the clinical utility of the point-of-care ultrasonographic data
      when caring for adult sepsis patients. METHODS: For this prospective before-and
      after study, patients with suspected sepsis received point-of-care
      ultrasonography to determine cardiac contractility, inferior vena cava diameter,
      and inferior vena cava collapsibility. Physician reports of treatment plans,
      presumed causes of observed vital sign abnormalities, and degree of certainty
      were compared before and after knowledge of point-of-care ultrasonographic
      findings. The clinical utility of point-of-care ultrasonographic data was also
      evaluated. RESULTS: Seventy-four adult sepsis patients were enrolled: 27 (37%)
      sepsis, 30 (40%) severe sepsis, 16 (22%) septic shock, and 1 (1%) systemic
      inflammatory response syndrome. After receipt of point-of-care ultrasonographic
      data, physicians altered the presumed primary cause of vital sign abnormalities
      in 12 cases (17% [95% confidence interval {CI} 8% to 25%]) and procedural
      intervention plans in 20 cases (27% [95% CI 17% to 37%]). Overall treatment plans
      were changed in 39 cases (53% [95% CI 41% to 64%]). Certainty increased in 47
      (71%) cases and decreased in 19 (29%). Measured on a 100-mm visual analog scale,
      the mean clinical utility score was 65 mm (SD 29; 95% CI 58 to 72), with
      usefulness reported in all cases. CONCLUSION: Emergency physicians found point-of
      care ultrasonographic data about cardiac contractility, inferior vena cava
      diameter, and inferior vena cava collapsibility to be clinically useful in
      treating adult patients with sepsis. Increased certainty followed acquisition of
      point-of-care ultrasonographic data in most instances. Point-of-care
      ultrasonography appears to be a useful modality in evaluating and treating adult
      sepsis patients.

PMID- 22633343
TI  - Combined use of 123I-metaiodobenzylguanidine (MIBG) scintigraphy and dopamine
      transporter (DAT) positron emission tomography (PET) predicts prognosis in drug
      induced Parkinsonism (DIP): a 2-year follow-up study.
AB  - DIP is a heterogeneous clinical syndrome; some patients develop persistent and
      worsening of parkinsonian symptoms after discontinuation of the offending drug,
      or Parkinson's disease (PD) reappears later after a full remission from DIP.
      However, it is difficult to predict the prognosis in patients with DIP. Herein,
      we evaluated whether the combined use of (18)F-N-(3-fluoropropyl)-2 beta-carbon
      ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET and cardiac MIBG scintigraphy
      can be used to help distinguish the prognosis in patients with DIP. Among 20
      patients enrolled, 16 showed normal DAT uptake and normal myocardial sympathetic
      innervation. After withdrawal of the suspected drugs, the patients experienced a
      clinical remission of parkinsonian motor symptoms within 3 months and did not
      experience any new movement symptoms after at least 2 years of follow-up. Two
      patients with a moderate decrease in DAT uptake and impaired sympathetic
      denervation showed worsening of motor manifestations 3 months after
      discontinuation of the drugs. Another two patients with normal DAT uptake and
      decreased MIBG uptake, presented full remission of motor symptoms within 2 months
      after discontinuation of the drugs. However, these two patients eventually
      developed parkinsonism within 2 years of the follow-up period. The follow-up
      scans revealed severe decreased DAT uptake in the putamen and similar ranges of
      cardiac sympathetic denervation. The results suggest that the combined use of
      these techniques can predict the prognosis of DIP and suggest a proper
      therapeutic plan for DIP.

PMID- 22633344
TI  - Effect of ocular alignment on emmetropization in children <10 years with
      amblyopia.
AB  - PURPOSE: To determine whether change in refractive error is associated with
      ocular alignment in 105 children 3 to <7 years of age who previously participated
      in a randomized trial comparing atropine and patching for moderate amblyopia.
      DESIGN: Prospective cohort study. METHODS: One hundred five children 3 to <7
      years of age previously participated in a randomized trial comparing atropine
      with patching for moderate amblyopia. Cycloplegic refraction was measured at
      baseline and 10 years of age. Ocular alignment at baseline was categorized as
      orthotropic, microtropic (1-8 Delta horizontal tropia), or heterotropic (>8 Delta
      horizontal tropia). Multivariate regression models evaluated whether change in
      spherical equivalent refractive error was associated with alignment category,
      after adjusting for age, baseline spherical equivalent refractive error, and type
      of amblyopia treatment. RESULTS: Between enrollment and the age 10-year
      examination, there was a decrease in spherical equivalent refractive error from
      hyperopia to less hyperopia (amblyopic eye: -0.65 diopter, 95% CI -0.85, -0.46;
      fellow eye: -0.39 diopter, 95% CI -0.58, -0.20). A greater decrease in amblyopic
      eye refractive error was associated with better ocular alignment category (P =
      .004), with the greatest decrease occurring in orthotropic patients. There was no
      relationship between ocular alignment category and change in fellow-eye
      refractive error. CONCLUSIONS: Among children treated for anisometropic,
      strabismic, or combined mechanism amblyopia, there is a decrease in amblyopic eye
      spherical equivalent refractive error to less hyperopia after controlling for
      baseline refractive error. This negative shift toward emmetropia is associated
      with ocular alignment, which supports the suggestion that better motor and
      sensory fusion promote emmetropization.

PMID- 22633345
TI  - Variation in prevalence of myopia between generations of migrant indians living
      in Singapore.
AB  - PURPOSE: To assess the influence of factors related to migration and
      acculturation on myopia in migrant Indians in Singapore. DESIGN: Population-based
      cross-sectional study. METHODS: A total of 3400 Singaporean Indians (75.6%
      response rate) aged over 40 years participated in this study. Information
      regarding country of birth, migration age, and language of interview were
      collected from interviews. Indians born outside of Singapore were defined as
      "first-generation" immigrants, while Indians born in Singapore were defined as
      "second-generation (or higher)" immigrants. Refraction was determined by
      autorefraction and refined by subjective refraction. Ocular biometry including
      axial length (AL), anterior chamber depth (ACD), and corneal radius (CR) were
      measured by partial coherence interferometry. Myopia and high myopia were defined
      as spherical equivalents (SE) of less than -0.5 diopter (D) for myopia, and < -5
      D for high myopia, respectively. RESULTS: The prevalence of myopia (30.2% vs 23.4
      %) and high myopia (4.8% vs 2.5%) were higher in second-generation immigrants
      compared with first-generation immigrants. Second-generation immigrants had
      longer AL (23.50 mm vs 23.37 mm, P = .004) than first-generation immigrants after
      multivariate adjustment. The excess prevalence of myopia was reduced by 37.5% but
      remained statistically significant (P = .02) after further controlling for
      educational level. Among first-generation immigrants, those migrating to
      Singapore before the age of 21 had significantly higher prevalence of myopia
      (odds ratio [OR]: 1.85; 95% confidence interval [CI]: 1.32, 2.59) and longer AL
      (regression coefficient: 0.27; 95% CI: 0.11, 0.43) than those migrating after 21
      years of age. Also, first-generation immigrants interviewed in English had higher
      prevalence of myopia (OR: 1.46; 95% CI: 1.00, 2.17) than their non-English
      interviewed counterparts. CONCLUSIONS: The prevalence of myopia among second
      generation (or higher) Indian immigrants in Singapore is higher than first
      generation immigrants. Country-specific environmental factors may be important
      for the increasing prevalence of myopia in Asia.

PMID- 22633346
TI  - Recipient endothelium may relate to corneal clearance in descemet membrane
      endothelial transfer.
AB  - PURPOSE: To describe corneal clearance after re-endothelialization of the
      recipient posterior stroma through Descemet membrane endothelial transfer (DMET)
      (ie, a "free-floating" donor Descemet graft in the recipient anterior chamber
      after descemetorhexis), in managing corneal endothelial disorders. DESIGN:
      Nonrandomized prospective study at a tertiary referral center. METHODS: Twelve
      eyes enrolled in our study, 7 suffering from Fuchs endothelial dystrophy and 5
      with bullous keratopathy. The clinical outcome was monitored by biomicroscopy,
      optical coherence tomography, confocal microscopy, endothelial cell density, and
      pachymetry measurements. RESULTS: All eyes operated on for Fuchs endothelial
      dystrophy showed corneal clearance, with pachymetry values returning to normal
      (533 +/-47 MUm). The denuded recipient stroma re-endothelialized with an average
      endothelial cell density of 797 (+/- 743) cells/mm(2) at 6 months after surgery.
      In contrast, none of the bullous keratopathy eyes showed any improvement
      throughout the follow-up period. CONCLUSION: DMET may be effective in the
      management of Fuchs endothelial dystrophy (primarily a Descemet membrane
      disorder), but not in bullous keratopathy (primarily an endothelial depletion).
      Apparently, the indication for surgery (ie, a "dystrophy" vs a "depletion" of
      recipient endothelial cells) relates to the capacity of the cornea to clear. This
      suggests that the remaining rim of recipient endothelium (after descemetorhexis)
      is involved in the re-endothelialization of the recipient posterior stroma after
      DMET.

PMID- 22633347
TI  - Chronic hypotony associated with the Boston type 1 keratoprosthesis.
AB  - PURPOSE: To report the occurrence of chronic hypotony as a complication following
      Boston type 1 keratoprosthesis (KPro) implantation and to determine associated
      risk factors. DESIGN: Retrospective case series. METHODS: The medical records of
      all patients undergoing KPro implantation between January 2004 and November 2010
      at the Wilmer Eye Institute were reviewed. Patients who developed chronic
      hypotony following Boston type 1 KPro implantation not attributable to anatomic
      problems (eg, retinal detachment, overfiltering glaucoma tube shunts, tissue
      necrosis with aqueous leak) or other causes were identified. Demographics and
      preoperative, intraoperative, and postoperative clinical findings were analyzed.
      Light microscopic examination of an enucleated globe as well as fibrous
      retroprosthetic membranes excised at the time of vitrectomy from another patient
      was performed. RESULTS: Sixty-eight eyes received KPro implantation over the
      study period. Six eyes experienced chronic hypotony, with a median time of 18.5
      months between KPro implantation and the onset of hypotony. The incidence of
      chronic hypotony in this series was calculated to be 3.7% at 1 year (95% CI =
      0.9%-14.0%) and 13.3% at 2 years (95% CI = 5.5%-30.0%). Of the 6 eyes that
      developed chronic hypotony, 5 had a previous history of glaucoma or ocular
      hypertension, but only 3 had a glaucoma drainage implant. All eyes progressing to
      chronic hypotony were noted to have a retroprosthetic membrane prior to the onset
      of hypotony. Cox regression modeling demonstrated an increased risk of chronic
      hypotony in eyes with retroprosthetic membranes (P < .01) but no increase in risk
      for older patients (P > .1), eyes with glaucoma drainage implants (P > .5), or a
      previous history of multiple donor corneal transplants (P > .5). CONCLUSION:
      Chronic hypotony can be a significant complication of KPro implantation and
      should be assessed carefully in eyes with retroprosthetic membranes. Further
      study of an association between hypotony and retroprosthetic membrane formation
      may be useful to gain insight into the mechanism of this complication and
      potential prevention or treatment options.

PMID- 22633348
TI  - Time-periodic characteristics in the morphology of idiopathic central serous
      chorioretinopathy evaluated by volume scan using spectral-domain optical
      coherence tomography.
AB  - PURPOSE: To investigate the time-period characteristics associated with
      morphologic changes in idiopathic central serous chorioretinopathy (CSC) using
      volume scans acquired by spectral-domain optical coherence tomography (SD-OCT).
      DESIGN: Retrospective, observational, cross-sectional case series. METHODS:
      Patients underwent visual acuity measurements, fundus examinations, fluorescein
      angiography, indocyanine green angiography, and SD-OCT volume scans. Patients
      were classified into 5 categories-acute CSC, early chronic (EC) CSC, late chronic
      (LC) CSC, sequelae of CSC, or recurrent CSC-according to the chronicity and the
      recurrence. We investigated the relationship between our classification and the
      detailed morphologic changes of the retinal pigment epithelium and outer retina
      that were observed in the SD-OCT images. RESULTS: A total of 76 eyes from 75
      patients were included in this study. Serous retinal detachment was relatively
      higher in acute CSC. Low to flat pigment epithelial detachments (PEDs) were most
      commonly observed in all stages of CSC, especially in LC CSC, but some
      semicircular PEDs were occasionally observed in eyes with acute or EC CSC.
      Retinal dragging with fibrin was most frequently observed in eyes that were in
      the early stage of acute CSC. A thickened posterior surface of the detached
      retina was most commonly observed in eyes with acute CSC, whereas a thinned
      posterior surface of the detached retina was observed in eyes with LC CSC.
      Hyperreflective dots and subretinal exudates were more commonly observed in eyes
      with EC and LC CSC than in eyes with acute CSC. In eyes with recurrent CSC, 2
      different patterns of SD-OCT findings were observed; these patterns resembled
      those that were found in either acute CSC or LC CSC. CONCLUSIONS: SD-OCT finding
      patterns in CSC eyes differ according to the chronicity and the recurrence of the
      disease. Detailed investigation of the retinal pigment epithelium and outer
      retina using SD-OCT could be useful for estimating the duration of CSC.

PMID- 22633349
TI  - Long-term effect of surface light scattering and glistenings of intraocular
      lenses on visual function.
AB  - PURPOSE: To investigate the long-term effect of surface light scattering and
      glistenings of various intraocular lenses (IOLs) on visual function and optical
      aberrations after cataract surgery. DESIGN: Case-control study. METHODS: Thirty
      five eyes that underwent implantation of a hydrophobic acrylic, silicone, or
      polymethyl methacrylate (PMMA) IOL more than 10 years ago were recruited. The
      scattering light intensity of the surface and internal matrix of the optic was
      measured using Scheimpflug photography. Visual acuity (VA) was measured using VA
      charts, and contrast VA and that with glare (glare VA) were examined using a
      contrast sensitivity tester. Ocular higher-order aberrations (HOAs) were measured
      using a Hartmann-Shack aberrometer. RESULTS: Mean scattering light intensity of
      the surface and internal matrix of the optic was significantly higher in the
      acrylic group than in the silicone and PMMA groups (P < .0001). Mean uncorrected
      VA, photopic and mesopic contrast VA and glare VA, and HOAs did not differ
      significantly among groups, although mean corrected VA in the acrylic group was
      significantly better than that in the other groups (P = .0023). Scattering light
      intensity of the surface and internal matrix did not correlate with VA, contrast
      VA, or glare VA, and did not correlate with ocular and internal optic HOAs in the
      acrylic group. CONCLUSIONS: At more than 10 years postoperatively, visual
      function, including contrast sensitivity, and ocular HOAs were comparable among
      eyes that received acrylic, silicone, and PMMA IOLs. Surface scattering and
      glistenings with the acrylic IOLs were not significantly correlated with visual
      function and optical aberrations.

PMID- 22633350
TI  - Glaucoma in patients with ocular chemical burns.
AB  - PURPOSE: To examine the development and management of glaucoma in patients with
      ocular chemical burns. DESIGN: Retrospective, observational case series. METHODS:
      setting: University of Washington Eye Clinics. patient population: Twenty-nine
      eyes (18 patients) with ocular chemical burns seen between 1997 and 2010 with a
      minimum of 3 months of follow-up. observation procedure: Eyes were graded using
      the Roper-Hall scale. main outcome measures: Long-term use of glaucoma
      medications (3 months or more) and need for glaucoma surgery. RESULTS: The mean
      age was 45 +/- 17 years, with a mean follow-up of 75 +/- 47 months (median, 66
      months). Roper-Hall grade III or IV eyes (n = 20) had significantly higher
      intraocular pressure at presentation (35.9 vs 16.4 mm Hg; P = .001) and over
      follow-up were more likely to require long-term glaucoma medications (P = .003)
      or to undergo glaucoma surgery (P = .016) than Roper-Hall grade I or II eyes.
      Thirteen eyes (12 Roper-Hall grade III or IV) underwent glaucoma surgery. Eight
      eyes underwent glaucoma tube implant surgery; 4 required at least 1 revision.
      Seven eyes underwent diode laser cyclophotocoagulation; 4 required repeat
      treatment. Most (89%) eyes had controlled intraocular pressure at the last follow
      up. However, 76% of eyes with visual acuity of 20/200 or worse at initial
      evaluation did not have improved vision at the last follow-up. CONCLUSIONS: Eyes
      with Roper-Hall grade III or IV ocular chemical burns were more likely to have
      glaucoma and to require surgery for it. Outcomes of glaucoma management generally
      were good, although tube implant surgeries often had complications requiring
      revision.

PMID- 22633351
TI  - Outcomes of deep anterior lamellar keratoplasty using the big-bubble technique in
      various corneal diseases.
AB  - PURPOSE: To report clinical outcomes of deep anterior lamellar keratoplasty
      (DALK) using the big-bubble technique in various original diagnoses. DESIGN:
      Prospective interventional study. METHODS: Single hospital study of 115
      unselected consecutive patients (131 eyes) with various diagnoses undergoing DALK
      using the big-bubble technique. The main outcome measures were intraoperative and
      postoperative complications, postoperative best spectacle-corrected visual acuity
      (BSCVA), and endothelial cell density (ECD). RESULTS: Descemet membrane was
      exposed successfully in 25 eyes (80.6%) with advanced keratoconus, 11 (73.3%)
      with chemical or thermal burns, 20 (71.4%) with corneal dystrophy, 21 (70%) with
      a herpes simplex (HSK) keratitis scar, 4 (36.4%) with moderate keratoconus, and 5
      (31.3%) with a bacterial keratitis scar (P < .05). Loosening of the sutures
      occurred in 24 eyes (23.8%) between postoperative4 and 7 months. Epithelial
      rejection was observed in 2 eyes and stromal rejection occurred in 5 eyes. BSCVA
      was improved in HSK scarring and corneal dystrophy vs keratoconus and corneal
      burns at 1 year (P < .05), but not after a mean follow-up of 21.4 months (P <
      .05). Patients who experienced stromal rejection had lower ECD than patients with
      no rejection at 18 and 24 months (P < .05). At all follow-up times after 6
      months, patients with multiple air injection attempts had lower ECD than patients
      with 1 injection attempt (P < .05). CONCLUSIONS: Different Descemet membrane
      exposure rates were observed in different diagnoses using the big-bubble
      technique. Both severe stromal rejection and additional manipulation may have a
      deleterious effect on the corneal endothelium.

PMID- 22633352
TI  - Ocular features in joint hypermobility syndrome/ehlers-danlos syndrome
      hypermobility type: a clinical and in vivo confocal microscopy study.
AB  - PURPOSE: To investigate ocular anomalies in joint hypermobility syndrome/Ehlers
      Danlos syndrome, hypermobility type (JHS/EDS-HT). DESIGN: Prospective, cross
      sectional study. METHODS: Forty-four eyes of 22 consecutive patients with an
      established diagnosis of JHS/EDS-HT and 44 eyes of 22 age- and gender-matched
      control subjects. Administration of a standardized questionnaire (Ocular Surface
      Disease Index) and a complete ophthalmologic examination, including assessment of
      best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure
      measurement, indirect ophthalmoscopy, tear-film break-up time, Schirmer I
      testing, axial length and anterior chamber depth measurement, corneal topography,
      corneal pachymetry, and confocal microscopy. Main outcome measures included
      comparing ocular anomalies in JHS/EDS-HT and control eyes. RESULTS: JHS/EDS-HT
      patients reported dry eye symptoms more commonly than controls (P < .0001).
      Scores of tear-film break-up time and Schirmer I test were significantly lower in
      JHS/EDS-HT eyes (P < .0001). Minor lens opacities were significantly more common
      in the JHS/EDS-HT group (13.6%; P < .05). Pathologic myopia with abnormal
      vitreous was found in 7 JHS/EDS-HT eyes (15.9%) and 0 controls (P = .01). Corneas
      were significantly steeper and the best-fit sphere index was significantly higher
      in JHS/EDS-HT group (P < .01). By confocal microscopy, the JHS/EDS-HT group
      showed lower density of cells in the superficial epithelium (P < .001) and higher
      density of stromal keratocytes in anterior and posterior stroma (P < .0001).
      CONCLUSIONS: The most consistent association of eye anomalies in the JHS/EDS-HT
      group included xerophthalmia, steeper corneas, pathologic myopia, and vitreous
      abnormalities, as well as a higher rate of minor lens opacities. These findings
      indicate the need for ophthalmologic survey in the assessment and management of
      patients with JHS/EDS-HT.

PMID- 22633353
TI  - The use of precut, gamma-irradiated corneal lenticules in Boston type 1
      keratoprosthesis implantation.
AB  - PURPOSE: To report the use of a sterile, gamma-irradiated corneal tissue without
      viable endothelium (VisionGraft Sterile Cornea; Tissue Banks International) in
      lieu of fresh donor cornea in Boston type 1 keratoprosthesis (KPro) implantation.
      DESIGN: Retrospective, interventional small case series. METHODS: Eleven eyes of
      11 patients underwent Boston type 1 keratoprosthesis implantation using
      VisionGraft Sterile Cornea between April 2009 and October 2010. Precut donut
      shaped corneal lenticules, using femtosecond laser, measuring 8.5 mm in diameter
      with a 3-mm central hole were used. RESULTS: Surgical procedures were uneventful.
      Complete corneal re-epithelization was noted within 10 days in all cases. No
      complications related to the donor cornea (eg, stromal necrosis, wound leak, or
      device extrusion) occurred over an average follow-up of 16.5 months. CONCLUSIONS:
      VisionGraft Sterile Cornea eliminates the need for use of fresh donor corneal
      tissue for Boston type 1 keratoprosthesis procedures, which makes this procedure
      a viable sight-restoring option when donor corneal tissues are not readily
      available.

PMID- 22633354
TI  - Frequency, genotype, and clinical spectrum of best vitelliform macular dystrophy:
      data from a national center in Denmark.
AB  - PURPOSE: To estimate the prevalence, genotype, and clinical spectrum of Best
      vitelliform macular dystrophy (Best disease). DESIGN: Retrospective epidemiologic
      and clinical and molecular genetic observational study. METHODS: setting:
      National referral center. participants: Forty-five individuals diagnosed with
      Best disease. observation procedures: Retrospective review of patients diagnosed
      according to clinical findings and sequencing of BEST1. Patients with recently
      established molecular genetic diagnosis were followed up including multifocal
      electroretinography (mfERG), spectral-domain optical coherence tomography (SD
      OCT), and fundus autofluorescence (FAF) imaging. main outcome measures:BEST1
      mutations, SD-OCT and FAF findings, mfERG amplitudes, prevalence estimate of Best
      disease. RESULTS: BEST1 mutations described previously in Danish patients with
      Best disease are reviewed. In addition, we identified a further 8 families and 1
      sporadic case, in whom 6 BEST1 missense mutations were found, 4 of which are
      novel. The mutation c.904G>T (p.Asp302Asn) was identified in members of 4
      unrelated families. Structural alterations ranged from precipitate-like
      alterations at the level of the photoreceptor outer segments (OS) to choroidal
      neovascularization. The extent of the former correlated with the reduction of
      retinal function. A prevalence estimate of Best disease in Denmark based on the
      number of diagnosed cases was 1.5 per 100 000 individuals. CONCLUSIONS: Our data
      expand the mutation spectrum of BEST1 in patients with Best disease. Alterations
      of the OS overlying lesions with subretinal fluid are similar to those seen in
      central serous retinopathy and may indicate impaired turnover of OS. Our
      frequency estimate confirms that Best disease is one of the most common causes of
      early macular degeneration.

PMID- 22633355
TI  - Disparities in adult vision health in the United States.
AB  - PURPOSE: To review the existing knowledge on vision health disparities in major
      adult vision health outcomes (age-related macular degeneration, diabetic
      retinopathy, glaucoma, cataract, refractive errors) and visual impairment and to
      identify knowledge gaps as related to the development of enhanced vision health
      surveillance in the United States. DESIGN: Literature review. METHODS: Analysis
      of relevant publications in the peer-reviewed literature. RESULTS: Prevalence
      data on vision health outcomes is limited to findings from a few key population
      based studies. Study populations are not representative of all persons living in
      the United States. Vision loss and visual impairment are more common with age,
      and there is racial variation in the specific causes of vision loss (underlying
      health conditions). Women are at greater risk of vision loss than men (even after
      adjusting for age). Vision-related disability and disparities in visual outcomes
      are monitored poorly at present. CONCLUSIONS: Data to assess and monitor trends
      in vision health disparities in the United States are not collected presently in
      a systematic fashion. This lack of data limits public health efforts to overcome
      barriers to eye care use and to improve vision outcomes.

PMID- 22633356
TI  - Digital evaluation of orbital development in chinese children with congenital
      microphthalmia.
AB  - PURPOSE: To evaluate the asymmetry of bilateral orbital development in Chinese
      children with congenital microphthalmia and to provide a criterion for tailoring
      treatment timing and therapy. DESIGN: Retrospective cohort study. METHODS: By
      combining multisection helical computerized tomography imaging with a computer
      aided design system, we measured 38 children between 0 and 6 years of age with
      congenital microphthalmia and 70 normal children of the same age group. Variables
      were measured, including orbital volume, depth, width, and height and eyeball
      volume. Displacement of the orbital rims was calculated by mirroring the
      unaffected orbit across the midsagittal plane of body. RESULTS: Significant
      differences were observed between the orbital volume, eyeball volume, orbital
      width, and orbital height of the affected and unaffected sides of children with
      congenital microphthalmia (P < .001). The difference between the orbital depth of
      the affected and unaffected sides was not significant (P = .055). Growth of the
      inferior and lateral rims retarded by an average of 3 mm, whereas that of the
      medial and superior rims retarded by less than 1 mm. CONCLUSIONS: The amount of
      decrease in orbital volume of children with congenital microphthalmia is related
      to the severity of the disease (decrease in size of the eye), rather than to age.
      Retarded orbital development is evident primarily in the inferior and lateral
      rims, correlating mostly with zygomatic and then maxilla and frontal bone. The
      growth of the affected orbit slows down or even stagnates by 3 years of age.
      Intervention therapy before 3 years of age was critical.

PMID- 22633357
TI  - Two-year corneal cross-linking results in patients younger than 18 years with
      documented progressive keratoconus.
AB  - PURPOSE: To report refractive, topographic, aberrometric, and tomographic
      outcomes 24 months after corneal cross-linking (CXL) in patients up to 18 years
      of age with progressive keratoconus. DESIGN: Prospective, interventional case
      series. METHODS: Forty eyes underwent riboflavin-ultraviolet A-induced CXL.
      Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA),
      sphere and cylinder, topography, aberrometry, tomography, and endothelial cell
      counts were evaluated at baseline and at 1, 3, 6, 12, and 24 months. RESULTS:
      Mean logarithm of the minimum angle of resolution baseline UCVA and BSCVA were
      0.79 +/- 0.21 and 0.39 +/- 0.10, respectively. Mean UCVA and BSCVA at 2 years
      were 0.58 +/- 0.18 and 0.20 +/- 0.09, respectively. The improvement in UCVA and
      BSCVA was significant throughout the postoperative follow-up (P < .05). Mean
      spherical equivalent refraction showed a significant decrease of 1.57 diopters
      (D) at 24 months (P = .02). Mean baseline simulated keratometry was 46.32 D in
      the flattest meridian and 51.48 D in the steepest meridian; at 2 years, the
      values were 45.30 D (P = .04) and 50.21 D (P = .07), respectively. For a 3-mm
      pupil, there was a significant reduction (P < .05) in whole eye (total), corneal,
      higher-order, and astigmatic wavefront aberrations at 24 months. A significant
      difference (P < .05) in total coma and total spherical aberration 2 years after
      CXL also was observed. Mean baseline pupil center pachymetry decreased
      significantly (P = .04) at 6 months, but recovered by 12 months and remained
      stable thereafter through the 2-year follow-up. Endothelial cell counts did not
      change significantly (P = .32). CONCLUSIONS: CXL improved UCVA and BSCVA in the
      study patients, most likely by significantly reducing corneal asymmetry and
      corneal as well as total wavefront aberrations.

PMID- 22633358
TI  - Visual field staging systems in glaucoma and the activities of daily living.
AB  - PURPOSE: To compare 8 clinically relevant methods of staging visual field (VF)
      damage in glaucoma with a performance-based measure of the activities of daily
      living and self-reported quality of life. DESIGN: Prospective cross-sectional
      study. METHODS: One hundred ninety-two patients with various types of glaucoma
      were evaluated at the Wills Eye Institute using standard monocular and binocular
      VF testing, as well as an objective, performance-based measure of visual function
      (the Assessment of Disability Related to Vision), and a subjective, standardized
      measure of quality of life (the 25-item National Eye Institute Visual Function
      Questionnaire). Binocular VFs were scored according to the Esterman and
      Integrated VF Systems. Monocular VFs were scored according to the mean defect,
      pattern standard deviation, Hodapp-Parrish-Anderson method, glaucoma staging
      system, glaucoma staging system 2, and the field damage likelihood scale. Partial
      Spearman correlations between VF staging systems, Assessment of Disability
      Related to Vision scores, and 25-item National Eye Institute Visual Function
      Questionnaire scores were calculated. RESULTS: Assessment of Disability Related
      to Vision scores and 25-item National Eye Institute Visual Function Questionnaire
      scores were associated most closely with the VF score in the better eye and the
      binocular VF scoring systems. CONCLUSIONS: The amount of binocular VF loss and
      the status of the better eye most accurately predict functional ability and
      quality of life in glaucoma.

PMID- 22633359
TI  - Re: Matthias Oelke, Francois Giuliano, Vincenzo Mirone, Lei Xu, David Cox, Lars
      Viktrup. Monotherapy with tadalafil or tamsulosin similarly improved lower
      urinary tract symptoms suggestive of benign prostatic hyperplasia in an
      international, randomised, parallel, placebo-controlled clinical trial. Eur Urol
      2012; 61:917-25.

PMID- 22633361
TI  - Female slings: where do we stand?

PMID- 22633363
TI  - Mapping of pain phenotypes in female patients with bladder pain
      syndrome/interstitial cystitis and controls.
AB  - BACKGROUND: Many bladder pain syndrome/interstitial cystitis (BPS/IC) patients
      report multiple pain locations outside the pelvis. No research has examined pain
      using a whole-body diagram, pain-associated adjustment factors, or the impact of
      pain in multiple body areas on patients' quality of life (QoL). OBJECTIVE:
      Compare and contrast pain in BPS/IC patients and controls using a whole-body
      diagram (visible body areas). Examine the association between patient adjustment
      factors and greater number of body pain areas (pain phenotypes). DESIGN, SETTING,
      AND PARTICIPANTS: Validated questionnaires were collected from diagnosed,
      tertiary-care, outpatient, female BPS/IC patients (n=193) and age-matched
      controls (n=115). Scales included a body pain area diagram, demographics/history,
      pain severity, BPS/IC symptoms, pain, depression, catastrophizing, and QoL.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cross-tabulation and analysis of
      variance models addressed the patient and control differences. RESULTS AND
      LIMITATIONS: Patients reported more pain than controls in all reported body
      areas. Four pain phenotypes were created based on increasing counts of body
      locations (BPS/IC only, BPS/IC+plus 1-3 additional locations, BPS/IC plus 4-9,
      BPS/IC >= 10). Patients reported more body pain locations, pain, urinary
      symptoms, depression, catastrophizing, and diminished QoL than controls. The
      increased-pain phenotype was associated with poorer psychosocial adjustment and
      diminished physical QoL, but catastrophizing and low scores for mental QoL
      remained stable across all patient groups. This study was cross-sectional,
      relying on correlation-based analyses, thus causality cannot be established.
      CONCLUSIONS: Patients reported numerous systemic pain symptoms outside the areas
      associated with the bladder/pelvic region, and increased numbers of body pain
      sites were associated with poorer patient outcomes (ie, pain severity,
      depression). This study illustrates the significant negative impact of pain on
      patient adjustment in BPS/IC. These findings suggest that clinicians carefully
      consider pain location distributions and the potential impact of body pain
      phenotypes during patient evaluation and treatment planning.

PMID- 22633364
TI  - Radical prostatectomy: yes or no? Your culture makes the difference.

PMID- 22633362
TI  - Neoadjuvant short-term intensive intravesical mitomycin C regimen compared with
      weekly schedule for low-grade recurrent non-muscle-invasive bladder cancer:
      preliminary results of a randomised phase 2 study.
AB  - BACKGROUND: The schedule for intravesical chemotherapy administration has not
      been definitively established in patients with low-grade recurrent non-muscle
      invasive bladder cancer (NMIBC). OBJECTIVE: To assess both the feasibility and
      the efficacy of a short-term intensive schedule of neoadjuvant intravesical
      chemotherapy in patients with recurrent NMIBC. DESIGN, SETTING, AND PARTICIPANTS:
      A randomised phase 2 clinical study included 54 patients with recurrent NMIBC who
      were submitted to neoadjuvant chemotherapy intravesical instillations according
      to two different timing schedules. The study was performed at a tertiary care
      referral centre. INTERVENTION: Intravesical mitomycin C (MMC) 40 mg/40 ml was
      administered according to a schedule of either one instillation per week for 6 wk
      (group 1) or three instillations per week for 2 wk (group 2) prior to
      transurethral resection (TUR). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Local and systemic toxicity were investigated using the US National Cancer
      Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.4.0
      questionnaire at each instillation and the SF-36 questionnaire at randomisation
      and before TUR. A video-recorded cystoscopy and TUR were performed within 14 d
      after treatment completion. RESULTS AND LIMITATIONS: Groups 1 and 2 each were
      assigned 27 cases. Two patients (7.4%) in group 2 could not complete the
      scheduled treatment because of severe lower urinary tract symptoms. No
      statistically significant difference in SF-36 domain score was documented pre-
      and post-treatment between groups. Likewise, no statistically significant
      difference in treatment-related toxicity according to the CTCAE v.4 questionnaire
      was registered. Twelve patients (44.4%) in group 1 and 19 patients (70.4%) in
      group 2 (p=0.04) had complete tumour response. The small number of patients
      included represents the main limitation of the study. CONCLUSIONS: The intensive
      short-term schedule of neoadjuvant chemotherapy is safe and without additional
      toxicity compared with the weekly regimen. The increased ablative effect may be
      explained by the improved adherence of the scheduled timing to the duplication
      rate of tumour cells.

PMID- 22633365
TI  - Biochemical recurrence after robot-assisted radical prostatectomy in a European
      single-centre cohort with a minimum follow-up time of 5 years.
AB  - BACKGROUND: Robot-assisted radical prostatectomy (RARP) is an increasingly
      commonly used surgical treatment option for prostate cancer (PCa); however, its
      longer-term oncologic results remain uncertain. OBJECTIVE: To report biochemical
      recurrence-free survival (BRFS) outcomes for men who underwent RARP >=5 yr ago at
      a single European centre. DESIGN, SETTING, AND PARTICIPANTS: A total of 944
      patients underwent RARP as monotherapy for PCa from January 2002 to December 2006
      at Karolinska University Hospital, Stockholm, Sweden. Standard clinicopathologic
      variables were recorded and entered into a secure, ethics-approved database made
      up of those men with registered domiciles in Stockholm. The median follow-up time
      was 6.3 yr (interquartile range: 5.6-7.2). OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: The outcome of this study was biochemical recurrence (BCR), defined as
      a confirmed prostate-specific antigen (PSA) of >=0.2 ng/ml. Kaplan-Meier survival
      plots with log-rank tests, as well as Cox univariable and multivariable
      regression analyses, were used to determine BRFS estimates and determine
      predictors of PSA relapse, respectively. RESULTS AND LIMITATIONS: The BRFS for
      the entire cohort at median follow-up was 84.8% (95% confidence interval [CI],
      82.2-87.1); estimates at 5, 7, and 9 yr were 87.1% (95% CI, 84.8-89.2), 84.5%
      (95% CI, 81.8-86.8), and 82.6% (95% CI, 79.0-85.6), respectively. Nine and 19
      patients died of PCa and other causes, respectively, giving end-of-follow-up
      Kaplan-Meier survival estimates of 98.0% (95% CI, 95.5-99.1) and 94.1% (95% CI,
      90.4-96.4), respectively. Preoperative PSA >10, postoperative Gleason sum >=4 +
      3, pathologic T3 disease, positive surgical margin status, and lower surgeon
      volume were associated with increased risk of BCR on multivariable analysis. This
      study is limited by a lack of nodal status and tumour volume, which may have
      confounded our findings. CONCLUSIONS: This case series from a single, high
      volume, European centre demonstrates that RARP has satisfactory medium-term BRFS.
      Further follow-up is necessary to determine how this finding will translate into
      cancer-specific and overall survival outcomes.

PMID- 22633366
TI  - Motion control of planar parallel robot using the fuzzy descriptor system
      approach.
AB  - This work presents the control of a two-degree of freedom parallel robot
      manipulator. A quasi-LPV approach, through the so-called TS fuzzy model and LMI
      constraints problems is used. Moreover, in this context a way to derive
      interesting control laws is to keep the descriptor form of the mechanical system.
      Therefore, new LMI problems have to be defined that helps to reduce the
      conservatism of the usual results. Some relaxations are also proposed to leave
      the pure quadratic stability/stabilization framework. A comparison study between
      the classical control strategies from robotics and the control design using TS
      fuzzy descriptor models is carried out to show the interest of the proposed
      approach.

PMID- 22633367
TI  - 12-Step participation reduces medical use costs among adolescents with a history
      of alcohol and other drug treatment.
AB  - BACKGROUND: Adolescents who attend 12-step groups following alcohol and other
      drug (AOD) treatment are more likely to remain abstinent and to avoid relapse
      post-treatment. We examined whether 12-step attendance is also associated with a
      corresponding reduction in health care use and costs. METHODS: We used difference
      in-difference analysis to compare changes in seven-year follow-up health care use
      and costs by changes in 12-step participation. Four Kaiser Permanente Northern
      California AOD treatment programs enrolled 403 adolescents, 13-18-years old, into
      a longitudinal cohort study upon AOD treatment entry. Participants self-reported
      12-step meeting attendance at six-month, one-year, three-year, and five-year
      follow-up. Outcomes included counts of hospital inpatient days, emergency room
      (ER) visits, primary care visits, psychiatric visits, AOD treatment costs and
      total medical care costs. RESULTS: Each additional 12-step meeting attended was
      associated with an incremental medical cost reduction of 4.7% during seven-year
      follow-up. The medical cost offset was largely due to reductions in hospital
      inpatient days, psychiatric visits, and AOD treatment costs. We estimate total
      medical use cost savings at $145 per year (in 2010 U.S. dollars) per additional
      12-step meeting attended. CONCLUSIONS: The findings suggest that 12-step
      participation conveys medical cost offsets for youth who undergo AOD treatment.
      Reduced costs may be related to improved AOD outcomes due to 12-step
      participation, improved general health due to changes in social network following
      12-step participation, or better compliance to both AOD treatment and 12-step
      meetings.

PMID- 22633368
TI  - Association of smoking and nicotine dependence with severity and course of
      symptoms in patients with depressive or anxiety disorder.
AB  - BACKGROUND: Previous research has indicated a strong association of smoking with
      depression and anxiety disorders, but the direction of the relationship is
      uncertain. Most research has been done in general population samples. We
      investigated the effect of smoking and nicotine dependence on the severity and
      course of depressive and anxiety symptoms in psychiatric patients. METHODS: Data
      came from the Netherlands Study of Depression and Anxiety (NESDA) including
      participants with a current diagnosis of depression and/or an anxiety disorder
      (N=1725). The course of smoking status and symptoms of depression, general
      anxiety, social anxiety, and agoraphobia were measured at baseline and after one
      and two years. Age, gender, education, alcohol use, physical activity, and
      negative life events were treated as covariates. RESULTS: At baseline, the
      symptoms of depression, general anxiety, and agoraphobia were more severe in
      nicotine-dependent smokers than in never-smokers, former smokers, and non
      dependent smokers. These differences remained after adjusting for covariates.
      Smaller differences were observed for severity of social anxiety which were no
      longer significant after controlling for covariates. Over a two-year follow-up,
      the improvement of depressive and anxiety symptoms was slower in nicotine
      dependent smokers than in the other groups even after controlling for covariates.
      There were no differences between the groups in the course of symptoms of social
      anxiety and agoraphobia over time. CONCLUSIONS: In psychiatric patients, smoking
      is associated with higher severity of depressive and anxiety symptoms, and with
      slower recovery, but only when smokers are nicotine-dependent.

PMID- 22633369
TI  - Migraine: a disorder of brain excitatory-inhibitory balance?
AB  - Migraine is a common disabling brain disorder whose key manifestations are
      recurrent attacks of unilateral headache and interictal hypersensitivity to
      sensory stimuli. Migraine arises from a primary brain dysfunction that leads to
      episodic activation and sensitization of the trigeminovascular pain pathway and
      as a consequence to headache. Major open issues concern the molecular and
      cellular mechanisms of the primary brain dysfunction(s) and of migraine pain. We
      review here our current understanding of these mechanisms, focusing on recent
      advances regarding migraine genetics, headache mechanisms, and the primary brain
      dysfunction(s) underlying migraine onset and susceptibility to cortical spreading
      depression, the neurophysiological correlate of migraine aura. We also discuss
      insights obtained from the functional analysis of familial hemiplegic migraine
      mouse models.

PMID- 22633371
TI  - Collaborating for a great congress and beyond.

PMID- 22633370
TI  - Antibiotic-induced bacterial cell death exhibits physiological and biochemical
      hallmarks of apoptosis.
AB  - Programmed cell death is a gene-directed process involved in the development and
      homeostasis of multicellular organisms. The most common mode of programmed cell
      death is apoptosis, which is characterized by a stereotypical set of biochemical
      and morphological hallmarks. Here we report that Escherichia coli also exhibit
      characteristic markers of apoptosis-including phosphatidylserine exposure,
      chromosome condensation, and DNA fragmentation-when faced with cell death
      triggering stress, namely bactericidal antibiotic treatment. Notably, we also
      provide proteomic and genetic evidence for the ability of multifunctional RecA to
      bind peptide sequences that serve as substrates for eukaryotic caspases, and
      regulation of this phenotype by the protease, ClpXP, under conditions of cell
      death. Our findings illustrate that prokaryotic organisms possess mechanisms to
      dismantle and mark dying cells in response to diverse noxious stimuli and suggest
      that elaborate, multilayered proteolytic regulation of these features may have
      evolved in eukaryotes to harness and exploit their deadly potential.

PMID- 22633372
TI  - Show us the evidence.

PMID- 22633373
TI  - To IRB or not to IRB: that is the question!

PMID- 22633374
TI  - Read the whole research article, not just the summary.

PMID- 22633375
TI  - Technology to assist in the prevention of retained surgical items.

PMID- 22633382
TI  - The circulating nurse's role in error recovery in the cardiovascular OR.
AB  - Nursing surveillance, an essential component of perioperative practice, includes
      the detection of and recovery from errors. However, error recovery is considered
      routine during nursing care and may go under-recognized. This study assessed the
      types of errors or potential errors that were detected and recovered by the
      circulating nurse during care of patients undergoing coronary artery or valve
      surgery. From June to September 2010, perioperative nurses observed 18 surgical
      procedures. An average of 11.11 errors or incidents occurred per procedure;
      however, 77% of all incidents were intercepted and the other 23% were either
      mitigated or ameliorated so no adverse outcomes occurred. This study demonstrates
      that nurses play an important role in ensuring patient safety and reinforces the
      necessity of vigilance in the OR, especially in regard to aseptic technique and
      surgical prepping.

PMID- 22633383
TI  - Informed consent: a study of the OR consenting process in New Zealand.
AB  - The outcome of the informed consenting process should be that patients are
      knowledgeable about their future procedure, but there is no guarantee that
      signing the informed consent form means that patients have understood the
      information that their health care providers have given to them. To evaluate the
      informed consenting process in an OR direct admissions department of a city
      hospital in New Zealand, we interviewed 18 surgical patients. We transcribed the
      audiotaped interviews and analyzed the data using a general inductive approach
      derived from Grounded Theory. Our analysis indicated that educational information
      was not always based on patients' previous knowledge or understanding, although
      most patients understood the surgical consenting process to be complete after
      they met with the physician and signed the form. Our study highlights that
      although patients spoke with their physicians and nurses, there was still a lack
      of understanding. Perioperative nurses are in a prime position to reinforce
      informed consent. They should actively support the consenting process and be
      proactive in collaborating with patients and physicians to ultimately ensure that
      the patient has every opportunity to make an informed decision.

PMID- 22633384
TI  - The nurse's role in providing information to surgical patients and family members
      in Turkey: a descriptive study.
AB  - In 2008, we conducted a nonexperimental, cross-sectional, descriptive study in
      the surgical services department of a hospital in Istanbul, Turkey, with the aim
      of determining how much information was required by perioperative patients and
      their family members, the extent to which this information was provided, and the
      role that nurses play in this process. We included a total of 394 outpatients and
      inpatients and their family members (ie, 197 patients, 197 family members) and 30
      nurses in the study. We collected the research data by using one questionnaire
      for patients, a second for family members of patients, and a third for nurses. We
      discovered that the patients and their family members wanted to be given more
      information about the surgical process than they had received. Patients wanted
      more information about the intraoperative period, whereas their family members
      wanted more information about the postoperative period. We also found that nurses
      were aware that they did not play an effective role in providing information to
      patients and their family members because of a lack of knowledge about what
      information they were responsible for providing and insufficient staffing. We
      concluded that nurses should know what education they are responsible for
      providing, put more effort into understanding patient and family member
      information needs, and plan a better means of providing information to meet those
      needs.

PMID- 22633385
TI  - Implementing AORN recommended practices for product selection.
AB  - This article focuses on the revised AORN "Recommended practices for product
      selection in perioperative practice settings." Hospitals and ambulatory surgery
      facilities should have protocols in place for product evaluation that includes a
      multidisciplinary team approach. The process for product evaluation and selection
      includes gathering information; establishing consistent requirements for product
      evaluation; performing a financial impact analysis; investigating a plan to
      standardize products; conducting an environmental impact analysis; determining
      whether to purchase single-use, reposable, or reusable products or reprocess
      single-use devices; developing an evaluation process based on objective criteria;
      and developing and implementing a comprehensive plan to introduce and use new
      products. Use of an evaluation tool that is based on objective criteria is one
      way to obtain valuable input during product evaluations. Because of varied roles
      and experiences, the perioperative RN is an integral member of the product
      selection committee.

PMID- 22633386
TI  - National Time Out Day: more than "a pause and a checklist".

PMID- 22633388
TI  - Milliliters and milligrams.

PMID- 22633390
TI  - Antiphospholipid syndrome masquerading as necrotising fasciitis.

PMID- 22633389
TI  - Refinements in reconstruction of penile skin loss using intra-operative
      prostaglandin injections, postoperative tadalafil application and negative
      pressure dressings.
AB  - PURPOSE: Penile shaft skin defects represent demanding reconstructive tasks
      because a high degree of flexibility and stability of the skin grafts are
      essential to allow regular erections and sexual intercourse. METHODS: A new
      concept of tailoring skin grafts to the erect penis by intra-operative
      application of prostaglandin E1 and postoperative stabilisation by negative
      pressure wound therapy and pharmacological expansion by tadalafil was tested on
      four patients with penile shaft skin defects. Graft take, stability, pliability,
      softness and aesthetic results were evaluated up to at least 12 months
      postoperatively. The ratio of the skin transplanted area in the non-erect
      compared to the erect penis (non-erect/erect ratio) and the ratio of the skin
      transplanted area in the erect penis at 12 months compared to intra-operatively
      (Post/Pre ratio) was determined to define the amount of graft contraction and
      flexibility. International Index of Erectile Function (IIEF)-5 scores were
      evaluated postoperatively. RESULTS: There were no complications. Graft take was
      97, 100, 100 and 100%. Stable skin grafts were achieved after 2 weeks. Sexual
      intercourse was possible at 2-3 months. The Post/Pre ratio was between 81 and 87%
      and proves comparably mild contracture rates. The non-erect/erect ratio of 50-72%
      shows how significantly undersized penile shaft skin grafts are when adjusted to
      the non-erect penis and that an adequate flexibility for erections can be
      reconstructed. IIEF-5 scores proved regular potency in three patients; one
      patient was no longer sexually active. CONCLUSIONS: With the new concept of
      tailoring the skin graft to the erect penis, pharmacological expansion and
      external stabilisation by vacuum-assisted closure (VAC) dressing the difficult
      task of penile skin reconstruction can be facilitated, accelerated and the
      functional and aesthetic outcome improved compared to earlier efforts or to
      results presented in the literature.

PMID- 22633391
TI  - Ultrasonography in PIP implant scanning: a cautionary tale.

PMID- 22633392
TI  - The effects of neoadjuvant and adjuvant chemotherapy on the surgical outcomes of
      breast reconstruction.
AB  - Breast reconstruction following mastectomy has become, in many centers the
      standard of care. An increasingly encountered trend is the use of neoadjuvant
      chemotherapy to downstage high stage tumors and to decrease tumor burden prior to
      definitive oncologic surgery. These agents clearly provide a survival benefit,
      but also have the potential to adversely affect the surgical course of immediate
      and delayed breast reconstruction. The use of new biologic and hormonal agents
      may also have effects on surgery and reconstruction. Furthermore,
      chemotherapeutic agents as a whole may impair cellular functions necessary for
      normal recovery from surgery. In this paper we present a concise review for the
      reconstructive surgeon on adverse effects of chemotherapeutic, hormonal and
      biologic agents used for treatment of breast cancer, important perioperative
      issues, and also discuss their potential effect on breast reconstruction.

PMID- 22633393
TI  - Reconstruction of penetrating injuries of the hand with dorsalis pedis composite
      free flaps: a series of 23 patients.
AB  - BACKGROUND: Reconstruction of severe hand injuries remains a challenge. We herein
      report the use of dorsalis pedis composite free flaps (DPCFFs) for the
      reconstruction of penetrating injuries of the hand. METHODS: From July 2001 to
      February 2009, 23 patients (15 males and 8 females), mean age of 26 years (range,
      17-48 years), with penetrating wounds of the hand were treated with DPCFFs. A
      second toe composite flap was used in cases of bone, joint, tendon and skin
      defects, and combined flaps were used for patients with only soft-tissue defects.
      Total joint transplantation using the proximal interphalangeal joint of the
      second toe was used in 10 cases, compound flaps using the metatarsophalangeal
      joint of the second toe were used in six, and combined dorsalis pedis flaps were
      used in seven cases of soft-tissue loss. RESULTS: All flaps survived, no bone
      nonunion or malunion occurred, and primary healing was achieved at all recipient
      and donor sites. Mean follow-up was 11 months (range, 6-27 months). In all cases,
      hand function was satisfactory and aesthetic outcome was good. Sensory recovery
      ranged from S2 to S3. In six cases with transplanted metatarsophalangeal joints,
      the mean range of flexion and extension was 45 degrees  (range, 30-70 degrees ).
      In 11 cases with transplanted proximal interphalangeal joints, the mean range of
      flexion and extension was 65 degrees  (range, 35-90 degrees ). No patient
      experienced difficulty walking. CONCLUSION: DPCFFs are useful for the repair of
      composite tissue defects of the hand. LEVELS OF EVIDENCE: III.

PMID- 22633394
TI  - Tissue expander with acellular dermal matrix for breast reconstruction infected
      by an unusual pathogen: Candida parapsilosis.
AB  - Infections occur in approximately 2-5% percent of women undergoing breast
      reconstruction by tissue expansion depending on patient characteristics and
      timing of reconstruction. Bacteria, specifically Staphylococci, are the most
      common pathogens. Treatment varies depending on the surgeon and the
      aggressiveness of the infection. We report a case of unilateral tissue expander
      infection with Candida parapsilosis in an otherwise healthy female undergoing
      immediate tissue expander placement after bilateral nipple-sparing mastectomies.
      The patient was treated with a one-stage irrigation, debridement, and tissue
      expander exchange as well as a 21-day course of oral antifungal therapy. Her
      infection resolved and she was able to complete her implant-based reconstruction.
      C. parapsilosis is usually responsible for infections in critically ill patients
      found in association with central lines, peritoneal dialysis catheters and
      prosthetic heart valves. The affinity of C. parapsilosis for foreign material
      makes it a causative agent worth considering in difficult to treat tissue
      expander infections.

PMID- 22633396
TI  - Reduced serum levels of adiponectin in elderly patients with major depression.
AB  - Recent studies have implicated adiponectin and other adipocytokines in brain
      function, particularly in processes related to memory and cognition. Blood levels
      of adiponectin are reduced in patients with primary cognitive disorders, such as
      Alzheimer's disease and mild cognitive impairment, and in adult patients with
      major depression. The aim of the present study is to determine serum levels of
      adiponectin in a sample of elderly patients with major depressive disorder (MDD)
      as compared to healthy older adults, and to examine the correlations between
      adiponectin levels and parameters indicative of mood and cognitive state. We
      recruited fifty-one unmedicated outpatients with late-life depression (LLD) and
      47 age-matched controls in this study. The diagnosis of MDD was made according to
      the DSM-IV criteria, and the severity of depressive episode was determined with
      the 21-item Hamilton Depression Scale (HDRS). Cognitive state was ascertained
      with the Cambridge Cognitive Test (CAMCOG) and the Mini-Mental State Examination
      (MMSE). Serum concentrations of adiponectin were determined using a sandwich
      ELISA method. Serum levels of adiponectin were significantly reduced in
      individuals with LLD (F = p < 0.001). Adiponectin level remained significantly
      reduced in after controlling for BMI index, scores on the CAMCOG, MMSE and HDRS
      and educational level (p < 0.001). Adiponectin levels showed a negative
      correlation with HDRS scores (r = -0.59, p < 0.001) and BMI index (r = -0.42, p <
      0.001); and showed a positive correlation with CAMCOG (r = 0.34, p < 0.01) and
      MMSE scores (r = 0.20, p = 0.05). The availability of circulating adiponectin is
      reduced in older adults with major depression, with likely implications on
      cognitive and mood state. Additional studies are required to determine whether
      this abnormality pertains to the pathophysiology of geriatric depression per se,
      or is a consequence of the morbid state.

PMID- 22633395
TI  - The effect of exposure to carcinogenic metals on histone tail modifications and
      gene expression in human subjects.
AB  - The precise mechanisms by which nickel and arsenic compounds exert their
      carcinogenic properties are not completely understood. In recent years,
      alterations of epigenetic mechanisms have been implicated in the carcinogenesis
      of compounds of these two metals. In vitro exposure to certain nickel or arsenic
      compounds induces changes in both DNA methylation patterns, as well as, in the
      levels of posttranslational modifications of histone tails. Changes in DNA
      methylation patterns have been reported in human subjects exposed to arsenic.
      Here we review our recent reports on the alterations in global levels of
      posttranslational histone modifications in peripheral blood mononuclear cells
      (PBMCs) of subjects with occupational exposure to nickel and subjects exposed to
      arsenic in their drinking water. Occupational exposure to nickel was associated
      with an increase in H3K4me3 and decrease in H3K9me2. A global increase in H3K9me2
      and decrease in H3K9ac was found in subjects exposed to arsenic. Additionally,
      exposure to arsenic resulted in opposite changes in a number of histone
      modifications in males when compared with females in the arsenic population. The
      results of these two studies suggest that exposure to nickel or arsenic
      compounds, and possibly other carcinogenic metal compounds, can induce changes in
      global levels of posttranslational histone modifications in peripheral blood
      mononuclear cells.

PMID- 22633397
TI  - A new model of care for familial hypercholesterolaemia: what is the role of
      cardiology?
AB  - Familial hypercholesterolaemia (FH) is a co-dominantly inherited disorder that
      causes marked elevation in plasma cholesterol and premature coronary heart
      disease. There are at least 45,000 people with FH in Australia and New Zealand,
      but most remain undiagnosed and undertreated. To bridge this gap in coronary
      prevention the FH Australasia Network has developed a model of care for FH. We
      present the executive summary, with a commentary contrasting the recommendations
      with other international guidelines and highlighting the role of the
      cardiologist.

PMID- 22633398
TI  - Inclusion of gene-gene and gene-environment interactions unlikely to dramatically
      improve risk prediction for complex diseases.
AB  - Genome-wide association studies have identified hundreds of common genetic
      variants associated with the risk of multifactorial diseases. However, their
      impact on discrimination and risk prediction is limited. It has been suggested
      that the identification of gene-gene (G-G) and gene-environment (G-E)
      interactions would improve disease prediction and facilitate prevention. We
      conducted a simulation study to explore the potential improvement in
      discrimination if G-G and G-E interactions exist and are known. We used three
      diseases (breast cancer, type 2 diabetes, and rheumatoid arthritis) as motivating
      examples. We show that the inclusion of G-G and G-E interaction effects in risk
      prediction models is unlikely to dramatically improve the discrimination ability
      of these models.

PMID- 22633399
TI  - RAD21 mutations cause a human cohesinopathy.
AB  - The evolutionarily conserved cohesin complex was originally described for its
      role in regulating sister-chromatid cohesion during mitosis and meiosis. Cohesin
      and its regulatory proteins have been implicated in several human developmental
      disorders, including Cornelia de Lange (CdLS) and Roberts syndromes. Here we show
      that human mutations in the integral cohesin structural protein RAD21 result in a
      congenital phenotype consistent with a "cohesinopathy." Children with RAD21
      mutations display growth retardation, minor skeletal anomalies, and facial
      features that overlap findings in individuals with CdLS. Notably, unlike children
      with mutations in NIPBL, SMC1A, or SMC3, these individuals have much milder
      cognitive impairment than those with classical CdLS. Mechanistically, these
      mutations act at the RAD21 interface with the other cohesin proteins STAG2 and
      SMC1A, impair cellular DNA damage response, and disrupt transcription in a
      zebrafish model. Our data suggest that, compared to loss-of-function mutations,
      dominant missense mutations result in more severe functional defects and cause
      worse structural and cognitive clinical findings. These results underscore the
      essential role of RAD21 in eukaryotes and emphasize the need for further
      understanding of the role of cohesin in human development.

PMID- 22633401
TI  - Local intraarterial tirofiban after formation of anterograde flow in patients
      with acute ischemic stroke: preliminary experience and short term follow-up
      results.
AB  - OBJECTIVE: Despite the risk of intracranial hemorrhage, combination therapy with
      intravenous recombinant tissue plasminogen activator and intraarterial mechanical
      thrombolysis can be effective for treatment of acute ischemic stroke. We
      investigated the feasibility and safety of intraarterial tirofiban following
      formation of anterograde flow after mechanical thrombolysis in acute ischemic
      stroke. METHODS: We analyzed data from consecutive patients with acute ischemic
      stroke, who underwent treatment with intraarterial thrombolysis. All patients
      were evaluated immediately and 7 days later by computed tomography scanning and
      magnetic resonance imaging scanning with magnetic resonance angiography. For
      clinical outcome analysis, we followed up the NIHSS score and modified Rankin
      Scale score during a period of 3 months. RESULTS: Sixteen patients underwent
      treatment. The mean baseline NIHSS score was 16.1 +/- 4.4 points. 75.1% of
      patients showed angiographic improvement; 43.8% and 31.3% had complete and
      partial recanalization, respectively. 53.3% and 56.3% showed clinical improvement
      and favorable outcome at 24 h and 3 months, respectively. One patient had
      symptomatic intracranial hemorrhage. CONCLUSIONS: Our results suggest that
      administration of local intraarterial tirofiban after anterograde flow formation
      is a viable treatment strategy for patients of acute ischemic stroke for reducing
      the risk of reocclusion after intraarterial thrombolysis.

PMID- 22633400
TI  - Genome-wide association study identifies candidate genes for male fertility
      traits in humans.
AB  - Despite the fact that hundreds of genes are known to affect fertility in animal
      models, relatively little is known about genes that influence natural fertility
      in humans. To broadly survey genes contributing to variation in male fertility,
      we conducted a genome-wide association study (GWAS) of two fertility traits
      (family size and birth rate) in 269 married men who are members of a founder
      population of European descent that proscribes contraception and has large family
      sizes. Associations between ~250,000 autosomal SNPs and the fertility traits were
      examined. A total of 41 SNPs with p <= 1 * 10(-4) for either trait were taken
      forward to a validation study of 123 ethnically diverse men from Chicago who had
      previously undergone semen analyses. Nine (22%) of the SNPs associated with
      reduced fertility in the GWAS were also associated with one or more of the ten
      measures of reduced sperm quantity and/or function, yielding 27 associations with
      p values < 0.05 and seven with p values < 0.01 in the validation study. On the
      basis of 5,000 permutations of our data, the probabilities of observing this many
      or more small p values were 0.0014 and 5.6 * 10(-4), respectively. Among the nine
      associated loci, outstanding candidates for male fertility genes include USP8, an
      essential deubiquitinating enzyme that has a role in acrosome assembly; UBD and
      EPSTI1, which have potential roles in innate immunity; and LRRC32, which encodes
      a latent transforming growth factor beta (TGF-beta) receptor on regulatory T
      cells. We suggest that mutations in these genes that are more severe may account
      for some of the unexplained infertility (or subfertility) in the general
      population.

PMID- 22633402
TI  - Putting it back: restoring lost soil carbon could benefit agriculture,
      ecosystems, and climate.

PMID- 22633403
TI  - Antimetabolite poisoning of cofactor biosynthesis.

PMID- 22633404
TI  - Discrimination between two endocannabinoids.

PMID- 22633405
TI  - Breaking down order to keep cells tidy.

PMID- 22633406
TI  - SnoaW/SnoaL2: a different two-component monooxygenase.

PMID- 22633407
TI  - Array-based functional screening of heparin glycans.
AB  - Array methodologies have become powerful tools for interrogation of glycan
      protein interactions but have critically lacked the ability to generate cell
      response data. Here, we report the development of a slide-based array method
      exemplified by measurement of activation of fibroblast growth factor signaling by
      heparin saccharides. Heparan sulfate-deficient Swiss 3T3 cells were overlaid onto
      an aminosilane-coated slide surface onto which heparin saccharides had been
      spotted and immobilized. The cells were transiently stimulated with FGF2 and
      immunofluorescence measured to assess downstream ERK1/2 phosphorylation.
      Activation of this signaling pathway response was restricted to cells exposed to
      heparin saccharides competent to activate FGF2 signaling. Differential activation
      of the overlaid cells by different-sized heparin saccharides was demonstrated by
      quantitative measurement of fluorescence intensity. This "glycobioarray" platform
      has significant potential as a generic tool for functional glycomics screening.

PMID- 22633409
TI  - Specificity of Dnmt1 for methylation of hemimethylated CpG sites resides in its
      catalytic domain.
AB  - The maintenance methylation of hemimethylated CpG sites by the DNA
      methyltransferase Dnmt1 is the molecular basis of the inheritance of DNA
      methylation patterns. Based on structural data and kinetics obtained with a
      truncated form of Dnmt1, an autoinhibition model for the specificity of Dnmt1 was
      proposed in which unmethylated DNA binds to Dnmt1's CXXC domain, which prevents
      its methylation. We have prepared CXXC domain variants that lost DNA binding.
      Corresponding full-length Dnmt1 variants did not display a reduction in
      specificity, indicating that the autoinhibition model does not apply in full
      length Dnmt1. Furthermore, we show that the Dnmt1 M1235S variant, which carries
      an exchange in the catalytic domain of the enzyme, has a marked reduction in
      specificity, indicating that the recognition of the hemimethylated state of
      target sites resides within the catalytic domain.

PMID- 22633408
TI  - The antibiotic CJ-15,801 is an antimetabolite that hijacks and then inhibits CoA
      biosynthesis.
AB  - The natural product CJ-15,801 is an inhibitor of Staphylococcus aureus, but not
      other bacteria. Its close structural resemblance to pantothenic acid, the vitamin
      precursor of coenzyme A (CoA), and its Michael acceptor moiety suggest that it
      irreversibly inhibits an enzyme involved in CoA biosynthesis or utilization.
      However, its mode of action and the basis for its specificity have not been
      elucidated to date. We demonstrate that CJ-15,801 is transformed by the uniquely
      selective S. aureus pantothenate kinase, the first CoA biosynthetic enzyme, into
      a substrate for the next enzyme, phosphopantothenoylcysteine synthetase, which is
      inhibited through formation of a tight-binding structural mimic of its native
      reaction intermediate. These findings reveal CJ-15,801 as a vitamin biosynthetic
      pathway antimetabolite with a mechanism similar to that of the sulfonamide
      antibiotics and highlight CoA biosynthesis as a viable antimicrobial drug target.

PMID- 22633410
TI  - Honaucins A-C, potent inhibitors of inflammation and bacterial quorum sensing:
      synthetic derivatives and structure-activity relationships.
AB  - Honaucins A-C were isolated from the cyanobacterium Leptolyngbya crossbyana which
      was found overgrowing corals on the Hawaiian coast. Honaucin A consists of (S)-3
      hydroxy-gamma-butyrolactone and 4-chlorocrotonic acid, which are connected via an
      ester linkage. Honaucin A and its two natural analogs exhibit potent inhibition
      of both bioluminescence, a quorum-sensing-dependent phenotype, in Vibrio harveyi
      BB120 and lipopolysaccharide-stimulated nitric oxide production in the murine
      macrophage cell line RAW264.7. The decrease in nitric oxide production was
      accompanied by a decrease in the transcripts of several proinflammatory
      cytokines, most dramatically interleukin-1beta. Synthesis of honaucin A, as well
      as a number of analogs, and subsequent evaluation in anti-inflammation and quorum
      sensing inhibition bioassays revealed the essential structural features for
      activity in this chemical class and provided analogs with greater potency in both
      assays.

PMID- 22633411
TI  - Dissecting heterogeneous molecular chaperone complexes using a mass spectrum
      deconvolution approach.
AB  - Small heat-shock proteins (sHSPs) are molecular chaperones that prevent
      irreversible aggregation through binding nonnative target proteins. Due to their
      heterogeneity, these sHSP:target complexes remain poorly understood. We present a
      nanoelectrospray mass spectrometry analysis algorithm for estimating the
      distribution of stoichiometries comprising a polydisperse ensemble of oligomers.
      We thus elucidate the organization of complexes formed between sHSPs and
      different target proteins. We find that binding is mass dependent, with the
      resultant complexes reflecting the native quaternary architecture of the target,
      indicating that protection happens early in the denaturation. Our data therefore
      explain the apparent paradox of how variable complex morphologies result from the
      generic mechanism of protection afforded by sHSPs. Our approach is applicable to
      a range of polydisperse proteins and provides a means for the automated and
      accurate interpretation of mass spectra derived from heterogeneous protein
      assemblies.

PMID- 22633412
TI  - Rapid determination of multiple linear kinase substrate motifs by mass
      spectrometry.
AB  - Kinase-substrate recognition depends on the chemical properties of the
      phosphorylatable residue as well as the surrounding linear sequence motif.
      Detailed knowledge of these characteristics increases the confidence of linking
      identified phosphorylation sites to kinases, predicting phosphorylation sites,
      and designing optimal peptide substrates. Here, we present a mass spectrometry
      based approach for determining linear kinase substrate motifs by elaborating the
      positional and chemical preference of the kinase for a phosphorylatable residue
      using libraries of naturally-occurring peptides that are amenable to peptide
      identification by commonly used proteomics platforms. We applied this approach to
      a structurally and functionally diverse set of purified kinases, which
      recapitulated their previously described substrate motifs and discovered
      additional ones, including preferences of certain kinases for phosphorylatable
      residues adjacent to peptide termini. Furthermore, we identify specific and
      distinguishable motif elements for the four members of the polo-like kinase (Plk)
      family and verify members of these motif elements for Plk1 in vivo.

PMID- 22633413
TI  - A nonpeptidic cathepsin S activity-based probe for noninvasive optical imaging of
      tumor-associated macrophages.
AB  - Macrophage infiltration into tumors has been correlated with poor clinical
      outcome in multiple cancer types. Therefore, tools to image tumor-associated
      macrophages could be valuable for diagnosis and prognosis of cancer. Herein, we
      describe the synthesis and characterization of a cathepsin S-directed, quenched
      activity-based probe (qABP), BMV083. This probe makes use of an optimized
      nonpeptidic scaffold leading to enhanced in vivo properties relative to
      previously reported peptide-based probes. In a syngeneic breast cancer model,
      BMV083 provides high tumor-specific fluorescence that can be visualized using
      noninvasive optical imaging methods. Furthermore, analysis of probe-labeled cells
      demonstrates that the probe primarily targets macrophages with an M2 phenotype.
      Thus, BMV083 is a potential valuable in vivo reporter for tumor-associated
      macrophages that could greatly facilitate the future studies of macrophage
      function in the process of tumorigenesis.

PMID- 22633414
TI  - Inhibitor mediated protein degradation.
AB  - The discovery of drugs that cause the degradation of their target proteins has
      been largely serendipitous. Here we report that the tert-butyl carbamate
      protected arginine (Boc(3)Arg) moiety provides a general strategy for the design
      of degradation-inducing inhibitors. The covalent inactivators ethacrynic acid and
      thiobenzofurazan cause the specific degradation of glutathione-S-transferase when
      linked to Boc(3)Arg. Similarly, the degradation of dihydrofolate reductase is
      induced when cells are treated with the noncovalent inhibitor trimethoprim linked
      to Boc(3)Arg. Degradation is rapid and robust, with 30%-80% of these abundant
      target proteins consumed within 1.3-5 hr. The proteasome is required for
      Boc(3)Arg-mediated degradation, but ATP is not necessary and the ubiquitin
      pathways do not appear to be involved. These results suggest that the Boc(3)Arg
      moiety may provide a general strategy to construct inhibitors that induce
      targeted protein degradation.

PMID- 22633415
TI  - Discovery of a two-component monooxygenase SnoaW/SnoaL2 involved in nogalamycin
      biosynthesis.
AB  - Nogalamycin is an anthracycline polyketide antibiotic that contains two
      deoxysugars, at positions C-1 and C-7. Previous biosynthetic studies conducted in
      vivo affiliated snoaL2 with an unusual C-1 hydroxylation reaction, but in vitro
      activity was not established. Here, we demonstrate that inactivation of either
      snoaL2 or snoaW resulted in accumulation of two nonhydroxylated metabolites,
      nogalamycinone and a novel anthracycline 3',4'-demethoxy-nogalose-nogalamycinone.
      The C-1 hydroxylation activity was successfully reconstructed in vitro in the
      presence of the two enzymes, NAD(P)H and the substrates. Based on relative
      reaction efficiencies, 3',4'-demethoxy-nogalose-nogalamycinone was identified as
      the likely natural substrate. A biosynthetic model was established where the
      atypical short-chain alcohol dehydrogenase SnoaW reduces the anthraquinone to a
      dihydroquinone using NADPH, which enables activation of oxygen and formation of a
      hydroperoxy intermediate. Finally, protonation of the intermediate by SnoaL2
      yields the 1-hydroxylated product.

PMID- 22633417
TI  - Vitamin K status in patients with short bowel syndrome.
AB  - BACKGROUND & AIMS: Available evidence suggests that patients with short bowel
      syndrome (SBS) might be at risk of vitamins A, D, E and B(1) deficiency. However,
      there is little clinical data describing the vitamin K status. Therefore, in the
      present study we aimed to assess the body resources of vitamin K in a subset of
      SBS patients. METHODS: The study comprised 33 patients aged 1 month to 16 years.
      PIVKA-II concentrations were determined in all subjects. RESULTS: In all studied
      subjects, coagulation parameters were normal. PIVKA-II levels indicative of
      vitamin K deficiency was found in 3 (9.1%) SBS patients. One patient had been
      receiving an additional intravenous vitamin K dose of 5 mg/week. In all SBS
      patients with cirrhosis and cholestasis, PIVKA-II concentrations were low (<2
      ng/ml). However, all patients with severe liver disease were receiving vitamin K
      several times a month. CONCLUSIONS: Vitamin K deficiency may appear in SBS
      patients.

PMID- 22633416
TI  - Tailoring enzymes involved in the biosynthesis of angucyclines contain latent
      context-dependent catalytic activities.
AB  - Comparison of homologous angucycline modification enzymes from five closely
      related Streptomyces pathways (pga, cab, jad, urd, lan) allowed us to deduce the
      biosynthetic steps responsible for the three alternative outcomes: gaudimycin C,
      dehydrorabelomycin, and 11-deoxylandomycinone. The C-12b-hydroxylated urdamycin
      and gaudimycin metabolites appear to be the ancestral representatives from which
      landomycins and jadomysins have evolved as a result of functional divergence of
      the ketoreductase LanV and hydroxylase JadH, respectively. Specifically, LanV has
      acquired affinity for an earlier biosynthetic intermediate resulting in a switch
      in biosynthetic order and lack of hydroxyls at C-4a and C-12b, whereas in JadH, C
      4a/C-12b dehydration has evolved into an independent secondary function replacing
      C-12b hydroxylation. Importantly, the study reveals that many of the modification
      enzymes carry several alternative, hidden, or ancestral catalytic functions,
      which are strictly dependent on the biosynthetic context.

PMID- 22633418
TI  - Comparative bioaccumulation kinetics of trace elements in Mediterranean marine
      sponges.
AB  - While marine organisms such as bivalves, seagrasses and macroalgae are commonly
      used as biomonitors for the environment pollution assessment, widely distributed
      sponges received little attention as potential helpful species for monitoring
      programmes. In this study, the trace element and radionuclide bioaccumulation and
      retention capacities of some marine sponges were estimated in a species
      comparative study using radiotracers technique. Six Mediterranean species were
      exposed to background dissolved concentrations of (110m)Ag, (241)Am, (109)Cd,
      (60)Co, (134)Cs, (54)Mn, (75)Se and (65)Zn allowing the assessment of the uptake
      and depuration kinetics for selected elements. Globally, massive demosponges
      Agelas oroides, Chondrosia reniformis and Ircinia variabilis displayed higher
      concentration factor (CF) than the erectile ones (Acanthella acuta, Cymbaxinella
      damicornis, Cymbaxinella verrucosa) at the end of exposure, suggesting that the
      morphology is a key factor in the metal bioaccumulation efficiency. Considering
      this observation, two exceptions were noted: (1) A. acuta reached the highest CF
      for (110m)Ag and strongly retained the accumulated metal without significant Ag
      loss when placed in depuration conditions and (2) C. reniformis did not
      accumulate Se as much as A. oroides and I. variabilis. These results suggest that
      peculiar metal uptake properties in sponges could be driven by specific
      metabolites or contrasting biosilification processes between species,
      respectively. This study demonstrated that sponges could be considered as
      valuable candidate for biomonitoring metal contamination but also that there is a
      need to experimentally highlight metal-dependant characteristic among species.

PMID- 22633419
TI  - Benefit of combined endoscopic sinus surgery and aesthetic rhinoplasty.
AB  - INTRODUCTION: Rhinoplasty is one of the most commonly performed aesthetic
      procedures today. Although nasal airway obstruction is frequently treated
      concomitantly with the aesthetic procedure, chronic sinusitis has typically
      postponed until full resolution of inflammatory symptoms. AIM OF THE STUDY: To
      investigate the feasibility of combining FESS with septorhinoplasty by measuring
      different outcomes including operative time, blood loss, post-operative edema of
      the upper and lower eyelids, periorbital ecchymosis, patient discomfort and
      complication rates. PATIENTS AND METHODS: The study included 20 patients with
      deformed nose associated with chronic rhinosinusitis (CRS) not responding to
      medical treatment for at least 3 continuous months, irrespective to sex, of ages
      20-60, and without any systemic diseases (study group), and 20 patients with
      deformed nose without any sinus problems (control group). RESULTS: There was no
      significant difference between the two groups in the different measured outcomes
      (P>0.05) except for the operative time which was significantly less in the
      control group (P<0.05). CONCLUSION: Concurrent rhinoplasty and endoscopic sinus
      surgery may be performed safely and effectively with minimal risks. Proper
      patient selection and sound intraoperative judgment can avoid potential
      complications.

PMID- 22633422
TI  - Update on clinical trials evaluating the effect of biologic therapy in patients
      with critical limb ischemia.
AB  - Critical limb ischemia (CLI) represents the most severe degree of peripheral
      arterial disease and is associated with significant morbidity and mortality. In
      patients with CLI who do not have revascularization options, major amputation is
      required within 1 year in as many as 40% of patients. Biologic therapies, which
      include gene therapy and cellular therapy, offer the potential to promote wound
      healing and prevent amputation in patients who otherwise have poor options for
      revascularization. Several recent phase 2 trials have shown acceptable safety and
      suggest that these biological therapies have the potential to improve outcomes in
      patients with "no-option" CLI. Phase 3 trials are now in progress. This report
      summarizes the recent results of, and future plans for, gene and cellular therapy
      clinical trials in patients with CLI.

PMID- 22633421
TI  - Aging reduces the accuracy of self-reported walking limitation in patients with
      vascular-type claudication.
AB  - BACKGROUND: The published correlations between treadmill performance and the
      Walking Impairment Questionnaire (WIQ) score are generally fair. We hypothesized
      that the slope of the relationship of maximal treadmill walking time to WIQ would
      be lower in older than in younger patients, resulting in (1) a fair correlation
      in the population considered as a whole and (2) different cutoff points of the
      WIQ score to predict the ability to complete 5 minutes of treadmill walking in
      different age groups. METHODS: A 9-month prospective study was performed among
      patients referred for vascular-type claudication. Patients were divided into
      three age groups by years: <60 (group 1, n = 91), 60 to 70 (group 2, n = 80), and
      >70 (group 3, n = 77). Patients self-completed the WIQ, which was corrected with
      a nurse, if necessary, and then completed a treadmill test. We calculated the
      correlation coefficient and slope of the relationship between the WIQ and maximal
      treadmill walking time. We used receiver operating characteristics curve analysis
      to estimate the accuracy of the WIQ score to determine the ability of the
      patients to complete 5 minutes of treadmill walking. RESULTS: Differences in
      slopes were significant between groups 1 vs 2 (P = .02), 2 vs 3 (P < .002), and 1
      vs 3 (P < .001). The R(2) for the regression lines also tended to decrease but
      was only significant between two extremes (1 vs 2, P = .11; 2 vs 3, P = .07; 1 vs
      3, P < .001). In patients aged <60 years (group 1), a WIQ score of 47 predicted
      the ability to complete a 5-minute test on treadmill with 86.8% accuracy (area
      under the receiver operating characteristics curve, 0.906; P < .001). The
      accuracy in predicting treadmill results from the WIQ score was fair in group 2
      and nonsignificant in group 3. CONCLUSIONS: Prediction of treadmill walking
      capacity from the WIQ score should account for age. The TransAtlantic Inter
      Society Consensus suggests that self-reported limitation has an equal weight as
      measured walking distance in the treatment choices and follow-up of patients with
      peripheral arterial disease. The WIQ should probably be used with caution in
      clinical routine, and constant-load treadmill testing is probably not the ideal
      candidate in elderly patients. New or adapted tools are likely needed in such
      patients but remain to be studied.

PMID- 22633420
TI  - Sex-based differences in the inflammatory profile of peripheral artery disease
      and the association with primary patency of lower extremity vein bypass grafts.
AB  - OBJECTIVE: This study was conducted to determine if there are sex-based
      differences in the inflammatory phenotype of patients undergoing lower extremity
      bypass (LEB) and if they correlate with clinical outcomes. METHODS: This was a
      retrospective analysis of a prospective cohort of 225 patients (161 men and 64
      women) who underwent autogenous vein LEB between February 2004 and May 2008.
      Fasting baseline blood samples were obtained before LEB, and the inflammatory
      biomarkers high-sensitivity C-reactive protein (CRP) and fibrinogen were
      assessed. All patients underwent ultrasound graft surveillance. CRP levels were
      dichotomized at 5 mg/L and fibrinogen levels at 600 mg/dL. RESULTS: There were no
      significant differences in age, race, history of hypertension or diabetes
      mellitus, body mass index, or coronary artery disease between men and women. Men
      were more likely to be current smokers (P = .02), have a history of
      hypercholesterolemia (P = .02), and be taking statins (P = .02). Women were more
      likely to present with critical limb ischemia (P = .03) and had higher median
      baseline CRP levels (5.15 mg/L; interquartile range [IQR], 1.51-18.62 mg/L) than
      men (2.70; IQR, 1.24-6.98 mg/L; P = .02). Median follow-up was 893 days (IQR, 539
      1315 days). A multivariable Cox proportional hazards model for primary vein graft
      patency showed a significant interaction between sex and CRP (P = .03) and
      fibrinogen (P = .02). After adjustment for key covariates, primary vein graft
      patency was significantly less in women with CRP >5 mg/L compared with women with
      CRP <5 mg/L (P = .02). No such difference was seen in men (P = .95). Primary
      graft patency was also decreased in women with fibrinogen >600 mg/dL vs women
      with fibrinogen <600 mg/dL (P = .002); again, this pattern was not evident in men
      (P = .19). CONCLUSIONS: Women undergoing LEB for advanced peripheral artery
      disease have a different inflammatory phenotype than men. Elevated baseline
      levels of CRP and fibrinogen are associated with inferior vein graft patency in
      women but not in men. These findings indicate an important interaction between
      sex and inflammation in the healing response of vein grafts for LEB. Women with
      elevated preoperative CRP and fibrinogen levels may benefit from more intensive
      postoperative graft surveillance protocols.

PMID- 22633423
TI  - A prospective randomized study comparing fibrin sealant to manual compression for
      the treatment of anastomotic suture-hole bleeding in expanded
      polytetrafluoroethylene grafts.
AB  - OBJECTIVE: The ideal hemostatic agent for treatment of suture-line bleeding at
      vascular anastomoses has not yet been established. This study evaluated whether
      the use of a fibrin sealant containing 500 IU/mL thrombin and synthetic aprotinin
      (FS; marketed in the United States under the name TISSEEL) is beneficial for
      treatment of challenging suture-line bleeding at vascular anastomoses of expanded
      polytetrafluoroethylene (ePTFE) grafts, including those further complicated by
      concomitant antiplatelet therapies. METHODS: Over a 1-year period ending in 2010,
      ePTFE graft prostheses, including arterio-arterial bypasses and arteriovenous
      shunts, were placed in 140 patients who experienced suture-line bleeding that
      required treatment after completion of anastomotic suturing. Across 24 US study
      sites, 70 patients were randomized and treated with FS and 70 with manual
      compression (control). The primary end point was the proportion of patients who
      achieved hemostasis at the study suture line at 4 minutes after start of
      application of FS or positioning of surgical gauze pads onto the study suture
      line. RESULTS: There was a statistically significant difference in the comparison
      of hemostasis rates at the study suture line at 4 minutes between FS (62.9%) and
      control (31.4%) patients (P < .0001), which was the primary end point. Similarly,
      hemostasis rates in the subgroup of patients on antiplatelet therapies were 64.7%
      (FS group) and 28.2% (control group). When analyzed by bleeding severity, the
      hemostatic advantage of FS over control at 4 minutes was similar (27.8% absolute
      improvement for moderate bleeding vs 32.8% for severe bleeding). Logistic
      regression analysis (accounting for gender, age, intervention type, bleeding
      severity, blood pressure, heparin coating of ePTFE graft, and antiplatelet
      therapies) found a statistically significant treatment effect in the odds ratio
      (OR) of meeting the primary end point between treatment groups (OR, 6.73; P <
      .0001), as well as statistically significant effects for intervention type (OR,
      0.25; P = .0055) and bleeding severity (OR, 2.59; P = .0209). The safety profile
      of FS was excellent as indicated by the lack of any related serious adverse
      events. CONCLUSIONS: The findings from this phase 3 study confirmed that FS is
      safe and its efficacy is superior to manual compression for hemostasis in
      patients with peripheral vascular ePTFE grafts. The data also suggest that FS
      promotes hemostasis independently of the patient's own coagulation system, as
      shown in a representative population of patients with vascular disease under
      single- or dual-antiplatelet therapies.

PMID- 22633426
TI  - Modified use of the Hemodialysis Reliable Outflow (HeRO) graft for salvage of
      threatened dialysis access.
AB  - The Hemodialysis Reliable Outflow (HeRO) graft (Hemosphere Inc, Eden Prairie,
      Minn) offers a new option to provide upper extremity arteriovenous (AV) dialysis
      access in patients with central venous occlusive disease. Creative use of this
      device can allow for salvage of failing or threatened AV fistulas and grafts. We
      present two patients who underwent a modified implantation of the HeRO device for
      immediate salvage of a malfunctioning AV access. Ipsilateral central venous
      occlusions were successfully overcome by anastomosing a HeRO device to the
      existing AV access and tunneled across the chest to the contralateral internal
      jugular vein.

PMID- 22633427
TI  - Symptomatic venous thromboembolism after femoral vein harvest.
AB  - OBJECTIVE: The femoral vein is increasingly utilized as a conduit in major
      arterial and venous reconstruction. However, perioperative complications,
      especially venous thromboembolism (VTE) associated with femoral vein harvest
      (FVH), are not well described. The purpose of this study was to determine the
      incidence and risk factors for the development of symptomatic VTE in patients who
      undergo FVH. METHODS: We conducted a retrospective cohort study of all patients
      who underwent FVH over a 5-year period at a single institution. Patient clinical
      characteristics, indications for surgery, postoperative venous duplex scans, and
      computerized tomography scans of the chest were gathered and reviewed from an
      electronic medical record query. Statistical analysis was performed to determine
      which factors correlate with development of perioperative complications after
      FVH. RESULTS: There were 57 patients (53% male; mean age, 62 years) who underwent
      58 FVHs. Of the procedures, 53% were performed for arterial reconstruction and
      47% for vascular reconstruction after cancer resection (85% portomesenteric
      reconstruction). Perioperative VTEs were diagnosed in 17 of 58 (29%) FVH
      procedures. Sixteen ipsilateral deep vein thromboses (DVTs) occurred distal to
      the FVH site and five (9%) occurred proximal to the FVH site. The incidence of
      VTE was significantly greater in patients with malignancy (52% vs 10%; P = .001),
      and 88% of all VTEs in this series were diagnosed in patients with cancer. All
      DVTs proximal to the FVH site and all DVTs in the contralateral extremity
      occurred in patients with malignancy. Pulmonary embolism occurred in two
      patients. No patients developed compartment syndrome or limb loss. Eight patients
      (14%) required FVH site wound debridement. CONCLUSIONS: VTE after FVH occurs more
      frequently in patients with malignancy. Aggressive and prolonged
      thromboprophylaxis and routine venous ultrasound surveillance are warranted after
      FVH in patients with malignancy.

PMID- 22633429
TI  - Risk factors for clinical failure after stent graft treatment for femoropopliteal
      occlusive disease.
AB  - OBJECTIVE: Optimal selection of a revascularization strategy in femoropopliteal
      occlusive disease (FPOD) remains controversial. Among endovascular treatment
      options for FPOD, covered stent placement has become increasingly used. We sought
      to examine the influence of clinical, anatomic, and device-related
      characteristics on the clinical performance of these devices. METHODS: This was a
      retrospective, single-center study of consecutively treated limbs that underwent
      Viabahn (W. L. Gore, Flagstaff, Ariz) stent graft placement for FPOD from 2005 to
      2010. Clinical, anatomic, and device-related characteristics were obtained from
      review of medical records and angiograms. End points were occurrence of any
      reintervention, major adverse limb event (eg, major amputation,
      thrombolysis/thrombectomy, or open bypass surgery), or thrombolysis/thrombectomy
      treatment alone. Univariate predictors were calculated and multivariate models
      constructed for each clinical end point using Cox proportional hazards models.
      RESULTS: The study cohort included 87 limbs in 77 unique patients, with a median
      follow-up time of 382 days. The indication for intervention was claudication in
      56%. In 25 cases (29%), the index procedure was a secondary intervention for
      FPOD, including treatment of in-stent restenosis in 22 cases (25%). Lesions
      treated included 45% TransAtlantic Inter-Society Consensus (TASC) II D and 58%
      chronic total occlusions. The observed Kaplan-Meier 1-year event rates for
      reintervention, major adverse limb event (MALE), and thrombolysis were 43%, 28%,
      and 17%, respectively. MALE occurred in 18 patients, nine of whom presented with
      acute limb ischemia; no patient underwent major amputation. Univariate predictors
      of negative outcomes included lack of dual-antiplatelet usage, advanced TASC II
      classification, smaller implant diameter, increased number of devices used,
      longer total implant length, and coverage of a patent distal collateral vessel.
      Multivariate analysis demonstrated that the presence of dual-antiplatelet usage
      was protective against all three outcomes, 5-mm device diameter was a risk factor
      for both reintervention and MALE, and the use of multiple devices and distal
      collateral coverage were significant risk factors for thrombolysis events.
      CONCLUSIONS: Reintervention is common in the first year after Viabahn placement
      for FPOD, with more than half of the events being a MALE. Procedural factors such
      as antiplatelet therapy, stent graft diameter, implant length/number, and distal
      collateral coverage are strongly associated with adverse clinical outcomes. These
      factors should be carefully considered to optimize patient selection and
      intraoperative decision making for this procedure.

PMID- 22633430
TI  - Perioperative administration of enoximone and renal function after cardiac
      surgery: a propensity-matched analysis.
AB  - BACKGROUND: Perioperative administration of enoximone has been shown to improve
      hemodynamics, organ function, and inflammatory response. Aim of the present study
      is to evaluate the impact of enoximone on postoperative renal function after on
      pump cardiac surgery. METHODS: A total of 3727 patients undergoing cardiac
      surgery at one Institution between May 2004 and November 2010 were reviewed. A
      propensity score was built and a 1:1 perfect matching was performed, providing
      two fairly comparable cohorts of 712 patients each, receiving or not enoximone
      after surgery. Renal function was evaluated by lower glomerular filtration rate
      (GFR) value reached postoperatively. RESULTS: Overall 30-day mortality rate was
      4.3% (62/1424). Cumulative incidence of postoperative renal failure (RF) was
      157/1424(11%), of which 99/1424(7%) needed renal replacement therapy. Mean lower
      postoperative GFR in patients who received or not enoximone was 63 +/- 30.1 and
      53.5 +/- 26.1 ml/min/1.73 m(2) (p<0.0001), respectively. At multivariable
      analysis age (OR2.75, p=0.0004), diabetes (OR1.82, p=0.006), preoperative GFR
      (OR3.81, p<0.0001), preoperative cardiogenic shock (OR1.65, p=0.004), previous
      cardiac surgery (OR2.12, p=0.0002), type of intervention (OR1.96, p=0.005), and
      enoximone (OR0.38, p=0.001) were found to be independently associated with
      postoperative RF. Logistic regression analysis showed that the administration of
      enoximone (OR0.41, p=0.0001), and of no inotropes (OR0.27, p<0.0001) were
      protective vs. the occurrence of postoperative RF. CONCLUSION: Patients
      perioperatively receiving enoximone showed a statistically significant better
      renal function after cardiac surgery.

PMID- 22633431
TI  - Pelvic inflammatory disease and myocardial infarction.

PMID- 22633433
TI  - Ventricular assist devices: bridge to continued employment.

PMID- 22633432
TI  - Number of shocks during elective cardioversion predicts long term recurrence of
      atrial fibrillation.

PMID- 22633434
TI  - Relation between poststenting peristent plaque components and late stent
      malapposition after drug-eluting stent implantation: virtual histology
      intravascular ultrasound analysis.
AB  - BACKGROUND: Impact of plaque composition on late stent malapposition (LSM) after
      drug-eluting stent (DES) implantation has not been evaluated. METHODS: We
      evaluated the relation between plaque components at poststenting peristent area
      (between external elastic membrane and stent areas) and LSM after DES
      implantation in 266 patients (314 native lesions; paclitaxel-eluting stent in 205
      lesions, sirolimus-eluting stent in 66 lesions, zotarolimus-eluting stent in 32
      lesions and everolimus-eluting stent in 11 lesions) in whom virtual-histology
      intravascular ultrasound was performed at index (poststenting) and follow-up
      (mean: 11.7 +/- 4.8 months). RESULTS: LSM occurred in 24 patients with 30 lesions
      (9.6%) and there were no significant differences in the incidences of LSM among 4
      DES groups [21/205 (10.2%) in paclitaxel-eluting stent, 6/66 (9.1%) in sirolimus
      eluting stent, 2/32 (6.3%) in zotarolimus-eluting stent and 1/11 (9.1%) in
      everolimus-eluting stent, p=0.5)]. Patients with LSM were presented with more
      acute myocardial infarction (50% vs. 28%, p=0.026) and were more diabetics (50%
      vs. 30%, p=0.030) compared with those without LSM. Lesions with LSM had more
      poststenting peristent %necrotic core (NC) volume compared with those without LSM
      (25.8 +/- 11.1% vs. 21.0 +/- 5.7%, p<0.001). Independent predictors of LSM were
      poststenting peristent %NC volume [odds ratio (OR); 1.216, 95% CI; 1.053-1.405,
      p=0.008], acute myocardial infarction (OR; 2.897, 95% CI; 1.675-4.118, p=0.029),
      and diabetes mellitus (OR; 2.413, 95% CI; 1.543-3.996, p=0.038). CONCLUSIONS:
      Poststenting peristent NC component especially in patients with acute myocardial
      infarction and in those with diabetes mellitus is associated with the development
      of LSM after DES implantation.

PMID- 22633435
TI  - Low vitamin D levels are related to left ventricular concentric remodelling in
      men of different ethnic groups with varying cardiovascular risk.

PMID- 22633436
TI  - Assessment of post-atrial switch baffle integrity using a modified dual extremity
      injection cardiac computed tomography angiography technique.

PMID- 22633437
TI  - Worsening renal function is not associated with response to treatment in acute
      heart failure.
AB  - BACKGROUND: About a fourth of acute decompensated heart failure (ADHF) patients
      develop renal dysfunction during their admission. To date, the association of
      ADHF treatment with the development of worsening renal function (WRF) remains
      contentious. Thus, we examined the association of WRF with changes in BNP levels
      and with mortality. METHODS: We performed retrospective chart review of patients
      admitted with ADHF who had BNP, eGFR, creatinine and blood urea nitrogen (BUN)
      values measured both on admission and discharge. Survival analysis was conducted
      using Cox proportional hazards model and correlation was measured using
      Spearman's rank correlation test. RESULTS: 358 patients admitted for ADHF were
      evaluated. WRF was defined as >20% reduction in eGFR from admission to discharge
      and response to treatment was assessed by DeltaBNP. There was a statistically
      significant reduction in BNP and increase in BUN during the admission. DeltaBNP
      did not correlate with either DeltaGFR or DeltaBUN. Patients who developed WRF
      and those who did not, had a similar reduction in BNP. On univariate survival
      analysis, DeltaBUN, but not DeltaeGFR, was associated with 1-year mortality. In
      multivariate Cox proportional hazards model, BUN at discharge was associated with
      1-year mortality (HR: 1.02, p<0.001), but DeltaeGFR and DeltaBUN were not
      associated with the primary endpoint. CONCLUSION: During ADHF treatment, DeltaBNP
      was not associated with changes in renal function. Development of WRF during ADHF
      treatment was not associated with mortality. Our study suggests that development
      of WRF should not preclude diuresis in ADHF patients in the absence of volume
      depletion.

PMID- 22633438
TI  - Virus chimeras for gene therapy, vaccination, and oncolysis: adenoviruses and
      beyond.
AB  - Several challenges need to be addressed when developing viruses for clinical
      applications in gene therapy, vaccination, or viral oncolysis, including specific
      and efficient target cell transduction, virus delivery via the blood stream, and
      evasion of pre-existing immunity. With rising frequency, these goals are tackled
      by generating chimeric viruses containing nucleic acid fragments or proteins from
      two or more different viruses, thus combining different beneficial features of
      the parental viruses. These chimeras have boosted the development of virus-based
      treatment regimens for major inherited and acquired diseases, including cancer.
      Using adenoviruses as the paradigm and prominent examples from other virus
      families, we review the technological and functional advances in therapeutic
      virus chimera development and recent successful applications that can pave the
      way for future therapies.

PMID- 22633439
TI  - Assessing risk of health care-acquired Legionnaires' disease from environmental
      sampling: the limits of using a strict percent positivity approach.
AB  - BACKGROUND: Elevated percent positivity (>=30%) of Legionella in hospital
      domestic water systems has been suggested as a metric for assessing the risk of
      health care-acquired Legionnaires' disease (LD). METHODS: We examined the
      validity of this metric by analyzing data from peer-reviewed studies containing
      reports of Legionella prevalence in hospital water (ie, percent positivity) and
      temporally matched reports of patients with health care-acquired LD. RESULTS: Our
      literature review identified 31 peer-reviewed publications reporting matched
      data. We abstracted a total of 206 data points, representing 119 hospitals, from
      these articles. We determined that the proposed 30% positivity metric has 59%
      sensitivity and 74% specificity (ie, a 41% false-negative rate and a 26% false
      positive rate). These notable error rates could have significant implications,
      given that we identified 16 peer-reviewed articles and 6 government guidance
      documents that referenced the 30% positivity metric as a risk assessment tool.
      CONCLUSIONS: Environmental sampling of hospital water distribution systems for
      Legionella can be an important component of risk management for LD. However, the
      possible consequence of using a percent positivity metric with low sensitivity
      and specificity is that many hospitals might fail to mitigate when a true risk is
      present, or might unnecessarily allocate limited resources to deal with a
      negligible risk.

PMID- 22633441
TI  - Lack of association between serum uric acid levels and outcome in acute ischemic
      stroke.
AB  - BACKGROUND: The prognostic value of serum uric acid (UA) in acute ischemic stroke
      is controversial. The aim of this study is to further analyse the relation
      between UA and outcome after acute ischemic stroke. METHODS: We analysed UA
      levels in blood samples collected within 6h of stroke onset from patients
      included in the placebo arm of the US and Canadian Lubeluzole Ischemic Stroke
      Study (LUB-INT-9). We compared mean serum UA levels in patients with and without
      early neurological improvement (>= 4 versus <4 points improvement on NIHSS after
      5 days) and in patients with good functional and poor functional outcome (mRS 0-2
      versus mRS 3-6). Multivariable logistic regression analyses were performed to
      adjust for possible confounders. RESULTS: UA levels of 226 patients were
      available for analysis. Mean serum UA levels were not significantly higher in
      patients with than without early neurological improvement (0.33 mmol/L versus
      0.30 mmol/L, p=0.070). The difference between patients with good and patients
      with poor functional outcome was borderline statistically significant (0.34
      mmol/L versus 0.31 mmol/L, p=0.050). After adjustment for confounders, higher
      serum UA levels were neither associated with early neurological improvement OR
      (1.30, 95% CI 0.98-1.73, p=0.069), nor with a good functional outcome (OR 1.09,
      95% CI 0.72-1.65, p=0.690). CONCLUSION: We found no association between admission
      serum UA levels and both short- and long-term outcome in acute ischemic stroke.

PMID- 22633442
TI  - Lack of response to rituximab therapy in patients with neuromyelitis optica: true
      non-responders or insufficient treatment?

PMID- 22633440
TI  - Translational research in immune senescence: assessing the relevance of current
      models.
AB  - Advancing age is accompanied by profound changes in immune function; some are
      induced by the loss of critical niches that support development of naive cells
      (e.g. thymic involution), others by the intrinsic physiology of long-lived cells
      attempting to maintain homeostasis, still others by extrinsic effects such as
      oxidative stress or long-term exposure to antigen due to persistent viral
      infections. Once compensatory mechanisms can no longer maintain a youthful
      phenotype the end result is the immune senescent milieu - one characterized by
      chronic, low grade, systemic inflammation and impaired responses to immune
      challenge, particularly when encountering new antigens. This state is associated
      with progression of chronic illnesses like atherosclerosis and dementia, and an
      increased risk of acute illness, disability and death in older adults. The
      complex interaction between immune senescence and chronic illness provides an
      ideal landscape for translational research with the potential to greatly affect
      human health. However, current animal models and even human investigative
      strategies for immune senescence have marked limitations, and the reductionist
      paradigm itself may be poorly suited to meet these challenges. A new paradigm,
      one that embraces complexity as a core feature of research in older adults is
      required to address the critical health issues facing the burgeoning senior
      population, the group that consumes the majority of healthcare resources. In this
      review, we outline the major advantages and limitations of current models and
      offer suggestions for how to move forward.

PMID- 22633443
TI  - Long-term neurotoxic effects of dimethylamine borane intoxication.
AB  - OBJECTIVES: To investigate the long-term neurotoxic effects in a patient with
      acute dimethylamine borane (DMAB) intoxication. PATIENTS: A 38-year-old man,
      working in a semiconductor factory, with acute DMAB intoxication presented with
      confusion, and drowsiness, followed by cognitive impairments and motor
      predominant axonal polyneuropathy. INVESTIGATIONS: We performed serial
      neurobehavioral assessments and functional neuroimaging studies, including brain
      (99m)Tc-TRODAT single photon emission computed tomography (SPECT) and brain
      positron emission tomography (PET) scan to monitor the long-term central nervous
      system (CNS) effects of DMAB intoxication. RESULTS: Neurobehavioral tests
      revealed a persistent impairment in episodic memory of visual retention semantic
      category retrieval and working memory of digit span (backward). Brain (99m)Tc
      TRODAT SPECT scan showed a lower radioactivity uptake in the left striatum and F
      18 FDG PET scan revealed a relatively decreased cerebral metabolism at the
      anterior cingulate gyrus and both frontal regions. Follow-up neurobehavioral
      tests showed that the cognitive improvements were mainly documented in
      intelligence, attention function, conceptual shift, perceptual motor speed,
      verbal learning and working memory but were limited in visual memory and
      executive functions. CONCLUSION: Patients with acute DMAB intoxication may have a
      long-lasting CNS toxicity on the cognitive dysfunction, parkinsonism, and an
      impaired metabolic activity of the brain. Clinical improvements may sustain
      during the long-term follow-up period.

PMID- 22633444
TI  - Adequate length of the surgical distal resection margin in rectal cancer: from
      the viewpoint of pathological findings.
AB  - BACKGROUND: Previous studies have not identified how to determine the optimal
      distal margin in rectal cancer based on histopathological diagnosis. We examined
      the surgical distal resection margin from a histopathological viewpoint. METHODS:
      We enrolled 629 patients. The type of distal spread was evaluated, and the
      maximum length of distal spread was measured using a micrometer. RESULTS: The
      frequencies of discontinuous spread type were 1.0%, 8.4%, 52.9%, and 81.5%, and
      the average lengths of distal spread were .5 +/- 1.3 mm, 7 +/- 1.8 mm, 2.7 +/-
      2.4 mm, and 10.0 +/- 9.5 mm for well-differentiated adenocarcinomas, moderately
      differentiated adenocarcinomas, solid (por1)-type poorly differentiated
      adenocarcinomas, and nonsolid (por2)-type poorly differentiated adenocarcinomas,
      (moderately vs solid [por1] type: P = .004), respectively. CONCLUSIONS: The
      surgical distal resection margin based on pathological diagnosis is longer
      somewhat than that based on macroscopic findings. Therefore, it is important to
      select surgical procedures with great care to ensure an adequate surgical distal
      resection margin.

PMID- 22633445
TI  - Total gastrectomy with "over-D1" lymph node dissection: what is the actual impact
      of age?
AB  - BACKGROUND: We aimed to evaluate risk factors for postoperative complications
      after total gastrectomy with "over-D1" lymphadenectomy. METHODS: Data on 161
      patients (54 cases aged >75 years: elderly group) operated on between 2005 and
      2011 were reviewed. Risk factors analyzed for complications (Clavien-Dindo
      classification) included sex, age, American Society of Anesthesiologists (ASA)
      grade, body mass index (BMI), pTNM stage, long-term antiplatelets therapy,
      operative time, and splenectomy. RESULTS: The median age of the study population
      was 71 (interquartile range [IQR] 62-77) years (79 [range 76-90] years for
      elderly patients vs 65 [range 33-75] years for the control group, P < .0001). ASA
      classification was the only baseline characteristic significantly different in
      the intergroup analysis; 79.6% of the elderly patients were in ASA class III to
      IV versus 39.2% of the controls (P < .0001). Univariate analysis showed that
      patient age, ASA score, BMI, and splenectomy were predictive of postoperative
      complications. Multivariate analysis confirmed ASA score and splenectomy as
      independent risk-factors. CONCLUSIONS: Regardless of age, fit elderly patients
      with operable gastric cancer should be candidates for the recommended standard
      extensive surgical resection provided that pre-existing comorbidities are
      considered.

PMID- 22633446
TI  - The pilot study: sphingomyelin-fortified milk has a positive association with the
      neurobehavioural development of very low birth weight infants during infancy,
      randomized control trial.
AB  - AIM: This study was a randomised control trial to examine the effects of
      sphingomyelin (SM), on the mental, motor and behavioural development of premature
      infants. PATIENTS AND METHODS: Randomised, double-blind controlled trial,
      enroling infants born with a birth weight of less than 1500 g between January
      2004 and October 2007 at Juntendo University Hospital, with follow-up to 18
      months. Twenty-four preterm babies were randomly assigned; 12 were assigned to a
      test group and fed SM-fortified milk (SM 20% of all phospholipids in milk) and 12
      were assigned to a control group (SM 13% of all phospholipids in milk). We
      analysed the composition of the plasma phospholipids and red-cell-membrane fatty
      acids, after which VEP, Fagan, BSID-II, attention and memory tests were
      performed. RESULTS: The percentage of SM in the total phospholipids was
      significantly higher in the trial group than in the control group at 4, 6 and 8
      weeks. The Behaviour Rating Scale of the BSID-II, the Fagan test scores, the
      latency of VEP, and sustained attention test scores at 18 months were all
      significantly better in the trial group than in the control group. CONCLUSION:
      This study is the first to report that nutritional intervention via
      administration of SM-fortified milk has a positive association with the
      neurobehavioural development of low-birth-weight infants. However, detailed
      studies on the effects of SM on longer-term development are required.

PMID- 22633447
TI  - Hepatectomy preserving drainage veins of the posterior section for liver
      malignancy invading the right hepatic vein: an alternative to right hepatectomy.
AB  - BACKGROUND: Although a right hepatectomy (RH) traditionally has been performed
      for liver tumors infiltrating the main trunk of the right hepatic vein (RHV), the
      presence of drainage veins of the posterior section (DVPS) beside the RHV
      provides a chance to preserve their draining area even if the main trunk of the
      RHV is removed. METHODS: Since 2005, we systematically have performed DVPS
      preserving hepatectomies whenever possible. In the present study, we describe our
      experience treating 12 consecutive patients who underwent this procedure.
      RESULTS: We performed the following types of liver resections concomitant with
      the main trunk of the RHV without packed red cell transfusion, liver failure, or
      90-day mortality: extended right anterior sectionectomy in 2 patients, extended
      segmentectomy 7 in 3, extended segmentectomy 8 in 2, and partial resection of
      segment 7 in 2 and segment 8 in 3. Postoperative morbidity was observed in 4
      (33%) cases, all of which had pleural effusion requiring a tap. A free resection
      margin was obtained in all patients. CONCLUSIONS: This procedure could be a
      useful alternative to RH, providing a chance for radical liver resection with
      minimal parenchymal sacrifice in selected patients with DVPS.

PMID- 22633449
TI  - Shedding light on brain circuits.

PMID- 22633448
TI  - The effectiveness of telehealth care on caregiver burden, mastery of stress, and
      family function among family caregivers of heart failure patients: a quasi
      experimental study.
AB  - BACKGROUND: Telehealth care was developed to provide home-based monitoring and
      support for patients with chronic disease. The positive effects on physical
      outcome have been reported; however, more evidence is required concerning the
      effects on family caregivers and family function for heart failure patients
      transitioning from the hospital to home. OBJECTIVE: To evaluate the effectiveness
      of nursing-led transitional care combining discharge plans and telehealth care on
      family caregiver burden, stress mastery and family function in family caregivers
      of heart failure patients compared to those receiving traditional discharge
      planning only. DESIGN: This is a quasi-experimental study design. METHODS: Sixty
      three patients with heart failure were assessed for eligibility and invited to
      participate in either telehealth care or standard care in a medical centre from
      May to October 2010. Three families refused to participate in data collection.
      Thirty families who chose telehealth care after discharge from the hospital to
      home comprised the experimental group; the others families receiving discharge
      planning only comprised the comparison group. Telenursing specialist provided the
      necessary family nursing interventions by 24-h remote monitoring of patients'
      health condition and counselling by telephone, helping the family caregivers
      successfully transition from hospital to home. Data on caregiver burden, stress
      mastery and family function were collected before discharge from the hospital and
      one month later at home. Effects of group, time, and group*time interaction were
      analysed using Mixed Model in SPSS (17.0). RESULTS: Family caregivers in both
      groups had significantly lower burden, higher stress mastery, and better family
      function at one-month follow-up compared to before discharge. The total score of
      caregiver burden, stress mastery and family function was significantly improved
      for the family caregivers in the experimental group compared to the comparison
      group at posttest. Two subscales of family function-Relationships between family
      and subsystems and Relationships between family and society were improved in the
      experimental group compared to the comparison group, but Relationships between
      family and family members was not different. CONCLUSIONS: The results provide
      evidence that telehealth care combined with discharge planning could reduce
      family caregiver burden, improve stress mastery, and improve family function
      during the first 30 days at home after heart failure patients are discharged from
      the hospital. Telenursing specialists cared caregivers with the concepts of
      providing transitional care to help them successful cross the critical transition
      stage.

PMID- 22633450
TI  - Expression and prognostic significance of thymidylate synthase (TS) in pancreatic
      head and periampullary cancer.
AB  - BACKGROUND: Pancreatic cancer has a dismal prognosis. Attempts have been made to
      improve outcome by several 5-FU based adjuvant treatment regimens. However, the
      results are conflicting. There seems to be a continental divide with respect to
      the use of 5-FU based chemoradiotherapy (CRT). Furthermore, evidence has been
      presented showing a different response of pancreatic head and periampullary
      cancer to 5-FU based CRT. Expression of thymidylate synthase (TS) has been
      associated with improved outcome following 5-FU based adjuvant treatment in
      gastrointestinal cancer. This prompted us to determine the differential
      expression and prognostic value of TS in pancreatic head and periampullary
      cancer. PATIENTS AND METHODS: TS protein expression was studied by
      immunohistochemistry on original paraffin embedded tissue from 212 patients
      following microscopic radical resection (R0) of pancreatic head (n = 98) or
      periampullary cancer (n = 114). Expression was investigated for associations with
      recurrence free (RFS), cancer specific (CSS) and overall survival (OS), and
      conventional prognostic factors. RESULTS: High cytosolic TS expression was
      present in 26% of pancreatic head tumours and 37% of periampullary tumours (p =
      .11). Furthermore, TS was an independent factor predicting favourable outcome
      following curative resection of pancreatic head cancer (p = .003, .001 and .001
      for RFS, CSS and OS, respectively). In contrast, in periampullary cancer, TS was
      not associated with outcome (all p > .10). CONCLUSION: TS, was found to be poorly
      expressed in both pancreatic head and periampullary cancer and identified as an
      independent prognostic factor following curative resection of pancreatic head
      cancer.

PMID- 22633451
TI  - A novel and hybrid composite transposon at the origin of acquisition of bla(RTG
      5) in Acinetobacter baumannii.
AB  - The genetic context of the gene coding for the novel variant of the class A beta
      lactamase RTG-5 (CARB-14), exhibiting two amino acid substitutions compared with
      the closest RTG-3 enzyme, was analysed in a clinical isolate of Acinetobacter
      baumannii. This novel variant exhibited a narrow-spectrum profile, as observed
      for RTG-3. Sequence analysis of the region flanking the 5' end of bla(CARB-14)
      identified a novel insertion sequence ISAba21 belonging to the IS3 family.
      Downstream of bla(CARB-14), another insertion sequence belonging to the IS3
      family named ISAba14 was identified. Analysis of the left-end extremity of
      ISAba21 and the right-end extremity of ISAba14 identified direct repeat sequences
      of 3 bp, likely being the signature of a transposition process. This is one of
      the few examples of a composite transposon made of different insertion sequences
      bracketing a gene coding for this novel carbenicillinase.

PMID- 22633453
TI  - Foxp3: shades of tolerance.
AB  - In this issue of Immunity, Darce et al. (2012) and Bettini et al. (2012)
      demonstrate that seemingly subtle alterations in the interaction of Foxp3 with
      its transcriptional partners have a ripple effect on the outcome of autoimmune
      phenotypes, worsening some while ameliorating others.

PMID- 22633454
TI  - Penetration resistance: PKR's other talent.
AB  - In this issue of Immunity, Irving et al. (2012) show that protein kinase R (PKR)
      regulates the cytoskeleton via an interaction with gelsolin. This alternative
      role for PKR prevents penetration of virions into the cell.

PMID- 22633452
TI  - Iron homeostasis regulates the activity of the microRNA pathway through poly(C)
      binding protein 2.
AB  - MicroRNAs (miRNAs) control gene expression by promoting degradation or repressing
      translation of target mRNAs. The components of the miRNA pathway are subject to
      diverse modifications that can modulate the abundance and function of miRNAs.
      Iron is essential for fundamental metabolic processes, and its homeostasis is
      tightly regulated. Here we identified iron chelators as a class of activator of
      the miRNA pathway that could promote the processing of miRNA precursors. We show
      that cytosolic iron could regulate the activity of the miRNA pathway through
      poly(C)-binding protein 2 (PCBP2). PCBP2 is associated with Dicer and promotes
      the processing of miRNA precursors. Cytosolic iron could modulate the association
      between PCBP2 and Dicer, as well as the multimerization of PCBP2 and its ability
      to bind to miRNA precursors, which can alter the processing of miRNA precursors.
      Our findings reveal a role of iron homeostasis in the regulation of miRNA
      biogenesis.

PMID- 22633455
TI  - Listeria monocytogenes: no spreading without NO.
AB  - In infectious disease immunology, inducible nitric oxide (NO) synthase-derived NO
      is believed to function primarily as an antimicrobial and immunoregulatory
      molecule. In this issue of Immunity, Cole et al. (2012) show that NO helps the
      intracellular bacteria Listeria monocytogenes to spread.

PMID- 22633456
TI  - Oxygenated lipids: a mode to WiPE out inflammation?
AB  - The immunologically silent clearance of apoptotic cells is crucial for
      maintaining self-tolerance. In this issue of Immunity, Uderhardt et al. (2012)
      reveal a mechanism by which lipid oxidation by tissue resident macrophages could
      inhibit the engulfment of apoptotic cells by inflammatory monocytes.

PMID- 22633457
TI  - IL-2: fine-tuning the germinal center reaction.
AB  - T follicular cells help B cells to drive germinal center formation. In this issue
      of Immunity, Ballesteros-Tato et al. (2012) demonstrate that high amounts of
      interleukin-2 inhibit production of this critical T effector subset.

PMID- 22633459
TI  - Regulation of actin dynamics by protein kinase R control of gelsolin enforces
      basal innate immune defense.
AB  - Primary resistance to pathogens is reliant on both basal and inducible immune
      defenses. To date, research has focused upon inducible innate immune responses.
      In contrast to resistance via cytokine induction, basal defense mechanisms are
      less evident. Here we showed that the antiviral protein kinase R (PKR) inhibited
      the key actin-modifying protein gelsolin to regulate actin dynamics and control
      cytoskeletal cellular functions under homeostatic conditions. Through this
      mechanism, PKR controlled fundamental innate immune, actin-dependent processes
      that included membrane ruffling and particle engulfment. Accordingly, PKR
      counteracted viral entry into the cell. These findings identify a layer of host
      resistance, showing that the regulation of actin-modifying proteins during the
      innate immune response bolsters first-line defense against intracellular
      pathogens and has a sustained effect on virus production. Moreover, these data
      provide proof of principle for a concept in which the cell cytoskeleton could be
      targeted to elicit broad antiviral protection.

PMID- 22633458
TI  - The chemokine superfamily revisited.
AB  - The chemokine superfamily consists of a large number of ligands and receptors. At
      first glance, this family appears redundant and their ligand-receptor
      relationships promiscuous, making its study challenging. However, analyzing this
      family from the evolutionary perspective greatly simplifies understanding both
      the organization and function of this apparently complex system. In particular,
      the functions of a subgroup of chemokines (designated homeostatic chemokines)
      have played pivotal roles in advancing our understanding of the organization and
      function of the cellular networks that shape the immune system. Here, we update
      the full scope of the human and mouse chemokine superfamilies and their
      relationships and summarize several important roles that homeostatic chemokines
      play in the immune system.

PMID- 22633460
TI  - ExPRESS shunt surgery: preferred glaucoma surgery in residency training?
AB  - It is important to equip future ophthalmic surgeons with appropriate surgical
      skills without compromising patient care. The ExPRESS implant surgery is very
      similar to trabeculectomy surgery in both efficacy and technique, but is less
      traumatic and may be prone to less postoperative hypotony and require less
      postoperative hypotensive medications. although affording a way to teach a novice
      surgeon the steps and technique of trabeculectomy and minimizing patient risk,
      ExPRESS implantation is a more expensive surgery that involves placing a foreign
      body in the eye. Further, needling an ExPRESS is a more technically challenging
      procedure than needling a trabeculectomy and more limited in its scope.

PMID- 22633461
TI  - Trabeculectomy versus ExPRESS shunt surgery in residency training.
AB  - The core curriculum for an ophthalmology residency training program should
      include surgical procedures relevant to a comprehensive ophthalmologist.
      Considerations include outcomes (success and complications), technical skill
      required, applicability to a wide range of disease, and cost. Using these
      metrics, trabeculectomy should be favored over ExPRESS shunt surgery.

PMID- 22633462
TI  - Regional projections of North Indian climate for adaptation studies.
AB  - Adaptation is increasingly important for regions around the world where large
      changes in climate could have an impact on populations and industry. The
      Brahmaputra-Ganges catchments have a large population, a main industry of
      agriculture and a growing hydro-power industry, making the region susceptible to
      changes in the Indian Summer Monsoon, annually the main water source. The
      HighNoon project has completed four regional climate model simulations for India
      and the Himalaya at high resolution (25km) from 1960 to 2100 to provide an
      ensemble of simulations for the region. In this paper we have assessed the
      ensemble for these catchments, comparing the simulations with observations, to
      give credence that the simulations provide a realistic representation of
      atmospheric processes and therefore future climate. We have illustrated how these
      simulations could be used to provide information on potential future climate
      impacts and therefore aid decision-making using climatology and threshold
      analysis. The ensemble analysis shows an increase in temperature between the
      baseline (1970-2000) and the 2050s (2040-2070) of between 2 and 4 degrees C and
      an increase in the number of days with maximum temperatures above 28 degrees C
      and 35 degrees C. There is less certainty for precipitation and runoff which show
      considerable variability, even in this relatively small ensemble, spanning zero.
      The HighNoon ensemble is the most complete data for the region providing useful
      information on a wide range of variables for the regional climate of the
      Brahmaputra-Ganges region, however there are processes not yet included in the
      models that could have an impact on the simulations of future climate. We have
      discussed these processes and show that the range from the HighNoon ensemble is
      similar in magnitude to potential changes in projections where these processes
      are included. Therefore strategies for adaptation must be robust and flexible
      allowing for advances in the science and natural environmental changes. 

PMID- 22633464
TI  - Late-onset Charcot-Marie-Tooth disease type 1B due to a novel mutation in the
      extracellular disulfide bridge of MPZ gene.

PMID- 22633465
TI  - Intraventricular aneurysms: case reports and review of the literature.
AB  - BACKGROUND: Intraventricular aneurysms are rare, with only 49 cases have been
      reported to date in the literature. Treatment of these aneurysms is difficult
      because of their deep location, small size, and specific angioarchitecture.
      METHODS: We report four patients with intraventricular aneurysms. In the third
      patient, the aneurysm self-occluded during procedure of endovascular
      embolization, which has previously not been reported in the literature. RESULTS:
      The first patient was discharged without definitive treatment of his
      intraventricular aneurysm and died 1 year later. The third patient's aneurysm
      self-occluded during the procedure of endovascular embolization procedure. The
      aneurysms of the second and fourth patients were successfully embolized by coils
      and Onyx, respectively. CONCLUSIONS: The conclusions drawn from our experience
      and a comprehensive review of the literature include the following: (1)
      intraventricular aneurysm should be considered in patients with isolated
      intraventricular hemorrhage; (2) intraventricular aneurysms are frequently very
      small (<5mm diameter), and therefore, cannot always be detected on initial
      angiography; (3) small intraventricular aneurysms cannot usually be clipped or
      occluded without sacrificing the parent artery; (4) if an intraventricular
      aneurysm is identified, it should be treated by endovascular embolization or
      clipping rather than conservative treatment; (5) endovascular embolization should
      be the first treatment option, and craniotomy can also be considered.

PMID- 22633466
TI  - The effects of substrate pre-treatment on anaerobic digestion systems: a review.
AB  - Focus is placed on substrate pre-treatment in anaerobic digestion (AD) as a means
      of increasing biogas yields using today's diversified substrate sources. Current
      pre-treatment methods to improve AD are being examined with regard to their
      effects on different substrate types, highlighting approaches and associated
      challenges in evaluating substrate pre-treatment in AD systems and its influence
      on the overall system of evaluation. WWTP residues represent the substrate type
      that is most frequently assessed in pre-treatment studies, followed by energy
      crops/harvesting residues, organic fraction of municipal solid waste, organic
      waste from food industry and manure. The pre-treatment effects are complex and
      generally linked to substrate characteristics and pre-treatment mechanisms.
      Overall, substrates containing lignin or bacterial cells appear to be the most
      amendable to pre-treatment for enhancing AD. Approaches used to evaluate AD
      enhancement in different systems is further reviewed and challenges and
      opportunities for improved evaluations are identified.

PMID- 22633467
TI  - Stabilisation of biodried municipal solid waste fine fraction in landfill
      bioreactor.
AB  - The biodrying process of solid waste is a pre-treatment for the bio-stabilisation
      of the municipal solid waste. This study aims to investigate the fate of the
      municipal solid waste fine fraction (MSWFF) resulting from a biodrying treatment
      when disposed in landfills that are operated as bioreactors. Biodried MSWFF was
      apparently stable due to its low moisture content that slows down the microbial
      activity. The lab-scale anaerobic bioreactors demonstrated that a proper moisture
      content leads to a complete biodegradation of the organic matter contained in the
      biodried MSWFF. Using a pilot-scale landfill bioreactor (LBR), MSWFF
      stabilisation was achieved, suggesting that the leachate recirculation could be
      an effective approach to accomplish the anaerobic biodegradation and
      biostabilisation of biodried MSWFF after landfilling. The biostabilisation of the
      material resulting from the LBR treatment was confirmed using anaerobic and
      aerobic stability indices. All anaerobic and aerobic indices showed a stability
      increase of approximately 80% of the MSWFF after treatment in the LBR. The
      similar values of OD7 and BMP stability indices well agree with the relationship
      between the aerobic and anaerobic indices reported in literature.

PMID- 22633468
TI  - Comparative study of bone repair in mandibular body osteotomy between metallic
      and absorbable 2.0 mm internal fixation systems. Histological and histometric
      analysis in dogs: a pilot study.
AB  - The objective of this study was to compare the bone repair along a mandibular
      body osteotomy stabilized with 2.0 mm absorbable and metallic systems. 12 male,
      adult mongrel dogs were divided into two groups (metallic and absorbable) and
      subjected to unilateral osteotomy between the mandibular third and fourth
      premolars, which was stabilized by applying two 4-hole plates. At 2 and 18 weeks,
      three dogs from each group were killed and the osteotomy sites were removed and
      divided equally into three parts: the upper part was labelled the tension third
      (TT), the lower part the compression third (CT), and the part between the TT and
      CT the intermediary third (IT). Regardless of the treatment system, union between
      the fragments was observed at 18 weeks and the CT showed more advanced stages of
      bone repair than the TT. Histometric analysis did not reveal any significant
      differences among the 3 parts or systems in the distance between bone fragments
      at 2 weeks. Although at 18 weeks the proportions of newly formed bone did not
      differ among TT, IT and CT, significantly enhanced bone formation was observed in
      all sections for the metallic group. The patterns of repair were distinct between
      treatments.

PMID- 22633469
TI  - Impact of 3D image-based PDR brachytherapy on outcome of patients treated for
      cervix carcinoma in France: results of the French STIC prospective study.
AB  - PURPOSE: In 2005 a French multicentric non randomized prospective study was
      initiated to compare two groups of patients treated for cervix carcinoma
      according to brachytherapy (BT) method: 2D vs 3D dosimetry. The BT dosimetric
      planning method was chosen for each patient in each center according to the
      availability of the technique. This study describes the results for 705 out of
      801 patients available for analysis. PATIENTS AND METHODS: For the 2D arm,
      dosimetry was planned on orthogonal X-Rays using low dose rate (LDR) or pulsed
      dose rate (PDR) BT. For the 3D arm, dosimetry was planned on 3D imaging (mainly
      CT) and performed with PDR BT. Each center could follow the dosimetric method
      they were used to, according to the chosen radioelement and applicator. Manual or
      graphical optimization was allowed. PATIENTS AND METHODS: Three treatment
      regimens were defined: Group 1: BT followed by surgery; 165 patients (2D arm: 76;
      3D arm: 89); Group 2: EBRT (+chemotherapy), BT, then surgery; 305 patients (2D
      arm: 142; 3D arm: 163); Group 3: EBRT (+chemotherapy), then BT; 235 patients, (2D
      arm: 118; 3D arm: 117). PATIENTS AND METHODS: The DVH parameters for CTVs (High
      Risk CTV and Intermediate Risk CTV) and organs at risk (OARs) were computed as
      recommended by GYN GEC ESTRO guidelines. Total doses were converted to equivalent
      doses in 2Gy fractions (EQD2). Side effects were prospectively assessed using the
      CTCAEv3.0. RESULTS: The 2D and 3D arms were well balanced with regard to age,
      FIGO stage, histology, EBRT dose and chemotherapy. For each treatment regimen, BT
      doses and volumes were comparable between the 2D and 3D arms in terms of dose to
      point A, isodose 60 Gy volume, dose to ICRU rectal points, and TRAK. RESULTS:
      Dosimetric data in the 3D arm showed that the dose delivered to 90% of the High
      Risk CTV (HR CTV D90) was respectively, 81.2Gy(alpha/beta10),
      63.2Gy(alpha/beta10) and 73.1Gy(alpha/beta10) for groups 1, 2 and 3. The
      Intermediate Risk (IR) CTV D90 was respectively, 58.5Gy(alpha/beta10),
      57.3Gy(alpha/beta10) and 61.7Gy(alpha/beta10) for groups 1, 2 and 3. For the
      OARs, doses delivered to D2cc ranged 60-70Gy(alpha/beta3) for the bladder, 33
      61Gy(alpha/beta3) for the rectum, and 44-58Gy(alpha/beta3) for the sigmoid
      according to the regimen. RESULTS: At 24 months, local relapse-free survival was
      91.9% and 100% in group 1, 84.7% and 93% in group 2, 73.9% and 78.5% in group 3;
      grade 3-4 toxicity rate was 14.6% and 8.9% in group 1, 12.5% and 8.8% in group 2,
      and 22.7% and 2.6% in group 3 for 2D and 3D arm. CONCLUSION: This multicentric
      study has shown that 3D BT is feasible and safe in routine practice. It has
      improved local control with half the toxicity observed with 2D dosimetry. The
      combined treatment with radiotherapy and surgery was more toxic than definitive
      radiotherapy. For patients with advanced tumors, it is necessary to improve
      coverage of target volumes without raising toxicity.

PMID- 22633470
TI  - The onchocerciasis chronicle: from the beginning to the end?
AB  - The year 2012 marks the 25th anniversary of the donation of ivermectin to fight
      onchocerciasis and the projected date for elimination of transmission of the
      disease in the Americas. This review looks at the history of onchocerciasis, from
      its discovery through to 2025, by which time it is projected that the disease
      will have been eliminated as a public health problem, except in a handful of sub
      Saharan countries, where it should be well on the way towards elimination.

PMID- 22633471
TI  - [Antibodies against the second extracellular loop of beta1-adrenergic receptor
      induce aortic endothelial dysfunction in Wistar rat].
AB  - PURPOSE: To evaluate the effect of active immunization with a peptide
      corresponding to the second extracellular loop of the human beta1-adrenoceptors
      (beta(1)-AR) on the reactivity of Wistar rat isolated aorta. METHODS: Nine-week
      old Wistar rats were actively immunized for 3months with a peptide corresponding
      to the second extracellular loop of the human beta(1)-AR. Specific
      immunoglobulins G (IgG) were characterized by Elisa and the bicinchonic acid
      protein assay and their functionality were tested in isolated ventricular
      cardiomyocytes (IVC) from control rats. Aortic rings isolated from control or
      immunized rats were mounted in organ baths. Then, contractile curves to
      phenylephrine (1nM to 300MUM) and relaxant curves to acetylcholine (1nM to
      100MUM) and isoprenaline (1nM to 30MUM) were established. RESULTS: Cell
      shortening increased dose-dependently in rat IVC superfused with IgG containing
      beta(1)-AR antibodies (10 or 25MUg/mL). Isoprenaline-induced positive inotropy
      was strongly reduced in IgG containing beta(1)-AR antibodies preincubated (3h)
      IVC. Phenylephrine-and acetylcholine-induced aortic responses were greatly
      inhibited in immunized rats compared to control ones. However, active
      immunization did not influence the isoprenaline-mediated relaxation. CONCLUSIONS:
      The present work confirms that beta(1)-AR antibodies directed against the second
      extracellular loop of beta(1)-AR induce a positive inotropic effect in adult rat
      IVC. Moreover, we demonstrated, for the first time, that 3-month immunization
      with beta(1)-AR peptide was associated with altered aortic endothelial function
      without change in the beta-AR-mediated vasorelaxation.

PMID- 22633472
TI  - Identical LDL-cholesterol lowering but non-identical effects on NF-kappaB
      activity: High dose simvastatin vs combination therapy with ezetimibe.
AB  - OBJECTIVE: Lowering LDL-cholesterol by statins has been proven to be associated
      with reduction of proinflammatory regulators e.g. activation of the transcription
      factor NF-kappaB. To our knowledge, anti-inflammatory potential of newer
      cholesterol lowering agents such as ezetimibe is less intensively studied.
      Therefore we analyzed the effects of equipotent LDL-lowering therapy with
      simvastatin alone compared to a combination with ezetimibe on NF-kappaB
      activation in peripheral blood mononuclear cells (PBMCs) of patients with type 2
      diabetes. METHODS: Thirty-one patients with type 2 diabetes were included in a
      double-blind, randomized trial receiving either 80 mg simvastatin (sim80; n = 10)
      or a combination of 10 mg simvastatin and 10 mg ezetimibe (sim10eze10; n = 11) or
      placebo (n = 9) for eight weeks. NF-kappaB binding activity and inflammatory
      markers (IL-6, hsCRP) were analyzed at baseline and after eight weeks of
      treatment. NF-kappaB binding activity was analyzed by electrophoretic mobility
      shift assay. IL-6 and hsCRP were measured by ELISA. RESULTS: After eight weeks of
      treatment LDL-cholesterol was lowered to the same extent in both treatment groups
      (p = 0.40) but not in placebo. However, patients taking sim80 showed a
      significant reduction of mononuclear NF-kappaB binding activity compared to
      baseline (p = 0.009) while no effect was observed in the sim10eze10 group (p =
      0.79). Similar differences in anti-inflammatory effects were also observed when
      analyzing hsCRP (sim80: p = 0.03; sim10eze10: p = 0.40) and IL-6 levels (sim80: p
      = 0.15; sim10eze10: p = 0.95). CONCLUSION: High dose simvastatin therapy reduces
      proinflammatory transcription factor NF-kappaB binding activity and hsCRP levels,
      while combination of low dose simvastatin with ezetimibe resulting in a similar
      LDL-reduction does not affect these inflammatory markers.

PMID- 22633473
TI  - Impact of systolic time intervals on the relationship between arterial stiffness
      and left ventricular hypertrophy.
AB  - OBJECTIVES: Arterial stiffness is correlated with left ventricular hypertrophy
      (LVH) and is susceptible to left ventricular performance. Therefore, if left
      ventricular systolic function is unknown, the relationship between arterial
      stiffness and LVH is controversial. This study was to assess the impact of the
      ratio of brachial pre-ejection period (bPEP) to brachial ejection time (bET), a
      marker of left ventricular systolic function, on the relationship between
      brachial-ankle pulse wave velocity (baPWV) and LVH. METHODS: A total of 1146
      patients were included in the study. The baPWV and bPEP/bET were measured using
      an ABI-form device. Patients were classified into four groups. Groups 1, 2, 3,
      and 4 were patients with bPEP/bET <= 0.38 and baPWV below the median, bPEP/bET >
      0.38 but baPWV below the median, bPET/bET <= 0.38 but baPWV above the median, and
      bPET/bET > 0.38 and baPWV above the median, respectively. RESULTS: Patients in
      groups 3 and 4 (high baPWV) and patients in group 2 (low baPWV but high bPEP/bET)
      were associated with increased left ventricular mass index (LVMI) and LVH (all P
      < 0.001). In a multivariate model, baPWV was significantly associated with LVMI
      (P = 0.007) and LVH (P = 0.025). Further adjustment for bPEP/bET made the
      association between baPWV and LVMI (P = 0.150) and LVH (P = 0.173) disappear.
      CONCLUSIONS: The bPEP/bET has an important impact on the relationship between
      baPWV and LVH. Therefore, the value of bPEP/bET obtained from the same
      examination should be considered while interpreting the relationship between
      baPWV and LVH.

PMID- 22633474
TI  - Epidemiological study of Enterobacteriaceae resistance to colistin in Sfax
      (Tunisia).
AB  - OBJECTIVES: The authors had for aim to monitor Enterobacteriaceae resistance to
      colistin, during 6 years (2005-2010), and to study the epidemiology of
      Enterobacteriaceae resistant strains isolated in the Sfax region (Tunisia).
      DESIGN: This retrospective study was carried out in the microbiology laboratory,
      at the Habib Bourguiba teaching hospital in Sfax. All strains of colistin
      resistant Enterobacteriaceae isolated from patients were studied. RESULTS: One
      hundred and twenty one strains of colistin resistant Enterobacteriaceae were
      isolated from 93 patients. Klebsiella pneumoniae was the most frequent species
      (60.2%), followed by Enterobacter cloacae (26.9%), and Escherichia coli (12.9%).
      Thirteen strains (E. cloacae) were heteroresistant to colistin. Eighty one
      isolates (87.1%) were resistant to third generation cephalosporins. The rate of
      resistance to colistin ranged from 0.09% for E. coli to 1.2% for K. pneumoniae,
      and 1.5% for E. cloacae. A progressively increasing colistin resistance was
      observed for K. pneumoniae. Most resistant strains were isolated from urine in
      the urology department. Previous exposure to colistin was reported in 59.2% of
      patients. Pulsed field gel electrophoresis typing revealed different clones.
      CONCLUSIONS: Colistin resistance in Enterobacteriaceae is a worrying phenomenon
      in Sfax. It is related to polyclonal diffusion. Continuous epidemiological
      monitoring and a rational use of colistin are necessary to limit the spreading of
      these colistin resistant strains and to maintain this antibiotic's effectiveness.

PMID- 22633475
TI  - [Condylomata acuminata of the urinary tract].

PMID- 22633476
TI  - Decreased fat oxidation during exercise in severe obstructive sleep apnoea
      syndrome.
AB  - AIM: To assess whether the severity of obstructive sleep apnoea syndrome (OSAS)
      is associated with altered fat oxidation (FO) during physical exercise in men
      with type 2 diabetes (T2DM) and/or the metabolic syndrome (MetS). METHODS: A
      total of 105 consecutive overweight or/and T2DM male patients were hospitalized
      for metabolic check-ups including bioimpedancemetry to measure lean body mass
      (LBM), standardized exercise calorimetry to assess FO, maximum fat oxidation
      (MFO) and carbohydrate oxidation (CHO), and OSAS screening using respiratory
      polygraphy. Twenty patients were classified as having severe OSAS, according to
      the apnoea/hypopnoea index (AHI), with greater than 30 events/h (mean AHI: 45.2+/
      14.3 events/h). They were group-matched for age, BMI, and the presence of T2DM
      and/or MetS with two other OSAS groups: mild (AHI<15 events/h [n=20]; mean AHI:
      8.8+/-4.5 events/h); and moderate (AHI>15 events/h and<30 events/h [n=20]; mean
      AHI: 23.7+/-4.2 events/h). RESULTS: MFO adjusted for LBM was severely decreased
      in the severe OSAS group (1.6+/-1.0 mg.min(-1).kgLM(-1)) compared with the
      moderate (2.5+/-0.9 mg.min(-1).kgLM(-1); P=0.008) and mild (2.9+/-0.8 mg.min(
      1).kgLM(-1); P=0.003) groups. All exercise-intensity levels (20%, 30%, 40% and
      60% of the theoretical maximum aerobic power) showed reduced FO levels between
      the severe and mild-to-moderate OSAS groups. However, no differences in CHO were
      seen at any level of exercise between groups. Pearson's correlation analysis
      showed that AHI and the oxygen desaturation index were negatively associated with
      MFO corrected for LBM (r=0.41 and r=0.37, respectively; P<0.005). CONCLUSION:
      OSAS severity is associated with altered FO during exercise.

PMID- 22633477
TI  - Sympathicotomy for isolated facial blushing: a randomized clinical trial.
AB  - BACKGROUND: Facial blushing is one of the most peculiar of human expressions. The
      pathophysiology is unclear, and the prevalence is unknown. Thoracoscopic
      sympathectomy may cure the symptom and is increasingly used in patients with
      isolated facial blushing. The evidence base for the optimal level of targeting
      the sympathetic chain is limited to retrospective case studies. We present a
      randomized clinical trial. METHODS: 100 patients were randomized (web-based,
      single-blinded) to rib-oriented (R2 or R2-R3) sympathicotomy for isolated facial
      blushing at two university hospitals during a 6-year period. Quality of life
      (QOL) was investigated preoperatively and after 12 months by Short Form 36. Local
      effects and side effects were assessed by questionnaire. RESULTS: The male/female
      ratio was 27/73. The median age was 29 years (range, 18-56 years. The response
      rate was 93%. QOL increased significantly in all social and mental domains in
      both groups. Overall, 85% of the patients had an excellent or satisfactory
      result, with no significant difference between the R2 procedure and the R2-R3
      procedure. Mild recurrence of facial blushing occurred in 30% of patients within
      the first year. One patient experienced Horner's syndrome. Compensatory sweating
      occurred in 93% of patients, gustatory sweating 36%, and dry hands in 66%; 13% of
      patients regretted the operation despite thorough preoperative selection and
      information. CONCLUSIONS: There were no significant differences in local effects
      or side effects between R2 and R2-R3 sympathicotomy for isolated facial blushing.
      Both were effective, and QOL increased significantly. Despite very frequent side
      effects, the vast majority of patients were satisfied. Surprisingly, many
      patients experienced mild recurrent symptoms within the first year; this should
      always be discussed with patients preoperatively.

PMID- 22633478
TI  - Oral and maxillofacial surgery: "publication hot spots" in the United Kingdom.
AB  - We aimed to evaluate the number of articles in the British Journal of Oral and
      Maxillofacial Surgery (BJOMS) written by consultants and trainees within
      deaneries in the UK. We reviewed the authorship of articles published between
      January 2010 and July 2011, and subdivided them by deanery and first author. In
      total, 76 full length articles were published (30 written by consultants and 46
      by trainees), and half came from the London, Wessex, and Mersey deaneries.
      Technical notes were mostly written by trainees; 5 of the 22 published came from
      London. A total of 38 short communications were published; most were from the
      Wessex (21%), Yorkshire and Humber (29%), and Mersey (13%) deaneries, and in 32%
      a consultant was first author. A league table of all publications showed that
      most came from Wessex (n=25), Mersey (n=23), and Yorkshire and Humber (n=23).
      Most publications by trainees came from Wessex (n=20), followed by Yorkshire
      (n=18) and London (n=11). The study shows that the amount of published material
      varies considerably between oral and maxillofacial surgery (OMFS) units in the
      UK. To realise their ambitions, potential trainees with an interest in research
      and publications may consequently find the best support in these deaneries.

PMID- 22633479
TI  - The prevalence of articular cartilage changes in the knee joint in patients
      undergoing arthroscopy for meniscal pathology.
AB  - PURPOSE: The purposes of this study were to evaluate the prevalence of articular
      cartilage changes in the knee joint and to analyze predictive factors for these
      changes in patients undergoing arthroscopy for meniscal pathology. METHODS:
      Between March 2005 and June 2009, 1,010 patients underwent arthroscopic
      meniscectomy or meniscal repair by the senior author. During surgery, a precise
      diagram was used to carefully note the presence, location, size, and Outerbridge
      grade of changes to the articular surfaces of the knee joint. The prevalence of
      articular cartilage changes was calculated for 6 age groups: younger than 20
      years, 20 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, and 60
      years or older. Demographic data including gender, ethnicity, smoking status, and
      body mass index (BMI) were acquired from patient charts. RESULTS: Overall, 48% of
      patients showed changes to the medial compartment, 25% to the lateral
      compartment, and 45% to the patellofemoral compartment. Eighty-five percent of
      patients aged 50 to 59 years and 86% of patients aged 60 years or older showed
      articular cartilage changes to at least 1 knee compartment. In contrast, only 13%
      of patients aged younger than 20 years and 32% of patients aged 20 to 29 years
      showed changes to at least 1 compartment. A significant relation was found
      between age and the development of articular cartilage changes in each of the 3
      compartments (P < .0001). BMI was also significantly related to articular
      cartilage changes in the medial and patellofemoral compartments (P < .0001) but
      not the lateral compartment (P = .08). CONCLUSIONS: This study shows a high
      prevalence of articular cartilage damage as defined by the Outerbridge
      classification in patients undergoing arthroscopic surgery for meniscal
      pathology. Risk factors that correlate with articular cartilage damage include
      increasing age, elevated BMI, medial compartment pathology, and knee
      contractures. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 22633480
TI  - Experimental infection of alpine goats with a Moroccan strain of peste des petits
      ruminants virus (PPRV).
AB  - Peste des petits ruminants virus (PPRV) recently caused a serious outbreak of
      disease in Moroccan sheep and goats. Alpine goats were highly susceptible to PPRV
      with mortality rates approaching 100%, as opposed to local breeds of sheep which
      were less susceptible to the disease. The relative susceptibility of alpine goats
      was investigated through an experimental infection study with the Moroccan strain
      of PPRV. Severe clinical signs were observed in the alpine goats with virus being
      excreted through ocular, nasal and oral routes. No difference in the severity of
      the disease in goats was observed with different inoculation routes and
      transmission of the virus by direct contact was confirmed. This study confirmed
      the susceptibility of the alpine goat to PPRV infection and describes a challenge
      protocol that effectively and consistently reproduced severe clinical signs of
      PPR in experimentally infected goats.

PMID- 22633481
TI  - Intestinal bacterial overgrowth includes potential pathogens in the carbohydrate
      overload models of equine acute laminitis.
AB  - Carbohydrate overload models of equine acute laminitis are used to study the
      development of lameness. It is hypothesized that a diet-induced shift in cecal
      bacterial communities contributes to the development of the pro-inflammatory
      state that progresses to laminar failure. It is proposed that vasoactive amines,
      protease activators and endotoxin, all bacterial derived bioactive metabolites,
      play a role in disease development. Questions regarding the oral bioavailability
      of many of the bacterial derived bioactive metabolites remain. This study
      evaluates the possibility that a carbohydrate-induced overgrowth of potentially
      pathogenic cecal bacteria occurs and that bacterial translocation contributes
      toward the development of the pro-inflammatory state. Two groups of mixed-breed
      horses were used, those with laminitis induced by cornstarch (n=6) or
      oligofructan (n=6) and non-laminitic controls (n=8). Cecal fluid and tissue
      homogenates of extra-intestinal sites including the laminae were used to
      enumerate Gram-negative and -positive bacteria. Horses that developed Obel grade2
      lameness, revealed a significant overgrowth of potentially pathogenic Gram
      positive and Gram-negative intestinal bacteria within the cecal fluid. Although
      colonization of extra-intestinal sites with potentially pathogenic bacteria was
      not detected, results of this study indicate that cecal/colonic lymphadenopathy
      and eosinophilia develop in horses progressing to lameness. It is hypothesized
      that the pro-inflammatory state in carbohydrate overload models of equine acute
      laminitis is driven by an immune response to the rapid overgrowth of Gram
      positive and Gram-negative cecal bacterial communities in the gut. Further equine
      research is indicated to study the immunological response, involving the
      lymphatic system that develops in the model.

PMID- 22633482
TI  - Co-infection of porcine dendritic cells with porcine circovirus type 2a (PCV2a)
      and genotype II porcine reproductive and respiratory syndrome virus (PRRSV)
      induces CD4(+)CD25(+)FoxP3(+) T cells in vitro.
AB  - Porcine circovirus associated disease (PCVAD) is currently one of the most
      economically important diseases in the global swine industry. Porcine circovirus
      type 2 (PCV2) is the primary causative agent, however co-infection with other
      swine pathogens such as porcine reproductive and respiratory syndrome virus
      (PRRSV) is often required to induce the full spectrum of clinical PCVAD. While
      the specific mechanisms of viral co-infection that lead to clinical disease are
      not fully understood, immune modulation by the co-infecting viruses likely plays
      a critical role. We evaluated the ability of dendritic cells (DC) infected with
      PRRSV, PCV2, or both to induce regulatory T cells (T(regs)) in vitro. DCs
      infected with PCV2 significantly increased CD4(+)CD25(+)FoxP3(+) T(regs) (p<0.05)
      and DCs co-infected with PRRSV and PCV2 induced significantly higher numbers of
      T(regs) than with PCV2 alone (p<0.05). Cytokine analysis indicated that the
      induction of T(regs) by co-infected DCs may be dependent on TGF-beta and not IL
      10. Our data support the immunomodulatory role of PCV2/PRRSV co-infection in the
      pathogenesis of PCVAD, specifically via T(reg)-mediated immunosuppression.

PMID- 22633483
TI  - Serological responses and clinical outcome after vaccination of mares and foals
      with equine herpesvirus type 1 and 4 (EHV-1 and EHV-4) vaccines.
AB  - Equine herpesvirus type 1 and type 4 (EHV-1 and EHV-4) cause infections of horses
      worldwide. While both EHV-1 and EHV-4 cause respiratory disease, abortion and
      myeloencephalopathy are observed after infection with EHV-1 in the vast majority
      of cases. Disease control is achieved by hygiene measures that include
      immunization with either inactivated or modified live virus (MLV) vaccine
      preparations. We here compared the efficacy of commercially available vaccines,
      an EHV-1/EHV-4 inactivated combination and an MLV vaccine, with respect to
      induction of humoral responses and protection of clinical disease (abortion) in
      pregnant mares and foals on a large stud with a total of approximately 3500
      horses. The MLV vaccine was administered twice during pregnancy (months 5 and 8
      of gestation) to 383 mares (49.4%), while the inactivated vaccine was
      administered three times (months 5, 7, and 9) to 392 mares (50.6%). From the
      vaccinated mares, 192 (MLV) and 150 (inactivated) were randomly selected for
      serological analyses. There was no significant difference between the groups with
      respect to magnitude or duration of the humoral responses as assessed by serum
      neutralization assays (median range from 1:42 to 1:130) and probing for EHV-1
      specific IgG isotypes, although neutralizing responses were higher in animals
      vaccinated with the MLV preparation at all time points sampled. The total number
      of abortions in the study population was 55/775 (7.1%), 9 of which were
      attributed to EHV-1. Seven of the abortions were in the inactivated and two in
      the MLV vaccine group (p=0.16). When foals of vaccinated mares were followed up,
      a dramatic drop of serum neutralizing titers (median below 1:8) was observed in
      all groups, indicating that the half-life of maternally derived antibody is less
      than 4 weeks.

PMID- 22633484
TI  - Skill development in graduate education.
AB  - The process of training new PhDs is complex and has significant dropout rates
      associated with loss of financial and time investments by the student, mentor,
      and program. One approach to improve graduate education is to make explicit the
      skills students need to develop and to put in place mechanisms to develop those
      skills.

PMID- 22633485
TI  - Lifting the threshold between life and death: SUMO and HDAC fine-tune HIPK2 to
      sense redox status.
AB  - In the current issue of Molecular Cell, de la Vega et al. (2012) propose an
      intriguing model for HIPK2 posttranslational modifications in response to
      oxidative stress, explaining how HIPK2 can possess both prosurvival as well as
      proapoptotic activities.

PMID- 22633486
TI  - MicroRNA factory: RISC assembly from precursor microRNAs.
AB  - RNA silencing requires assembly of an effector complex, RNA-induced silencing
      complex (RISC), composed of a small RNA and the Ago protein. In this issue of
      Molecular Cell, Liu et al. (2012) provide insights of miRNP/RISC assembly
      pathways in mammals, using an in vitro human RISC assembly assay programmed by
      pre-miRNAs.

PMID- 22633487
TI  - A perspective on mammalian caspases as positive and negative regulators of
      inflammation.
AB  - Members of the caspase family of cysteine proteases coordinate the morphological
      and biochemical events that typify apoptosis. However, neutralization of caspase
      activity in mammals fails to block death in response to most proapoptotic
      stimuli. This is because many cell death triggers provoke mitochondrial
      dysfunction upstream of caspase activation as a consequence of BAX/BAK channel
      opening. Although genetic or pharmacological inactivation of caspases fails to
      block cell death in most instances, it does convert the phenotype from apoptosis
      to necrosis. This has important implications for how the immune system responds
      to such cells, as necrotic cells provoke inflammation whereas apoptotic cells
      typically do not. Here, we propose an alternative perspective on apoptosis
      associated caspase function by suggesting that these proteases are activated, not
      to kill, but to extinguish the proinflammatory properties of dying cells. This
      perspective unifies the mammalian caspase family as either positive or negative
      regulators of inflammation.

PMID- 22633488
TI  - Mode of regulation and the insulation of bacterial gene expression.
AB  - A gene can be said to be insulated from environmental variations if its
      expression level depends only on its cognate inducers, and not on variations in
      conditions. We tested the insulation of the lac promoter of E. coli and of
      synthetic constructs in which the transcription factor CRP acts as either an
      activator or a repressor, by measuring their input function-their expression as a
      function of inducers-in different growth conditions. We find that the promoter
      activities show sizable variation across conditions of 10%-100% (SD/mean). When
      the promoter is bound to its cognate regulator(s), variation across conditions is
      smaller than when it is unbound. Thus, mode of regulation affects insulation:
      activators seem to show better insulation at high expression levels, and
      repressors at low expression levels. This may explain the Savageau demand rule,
      in which E. coli genes needed often in the natural environment tend to be
      regulated by activators, and rarely needed genes by repressors. The present
      approach can be used to study insulation in other genes and organisms.

PMID- 22633489
TI  - Cell-type-specific control of enhancer activity by H3K9 trimethylation.
AB  - Cell-type-specific control of gene expression is critical for the development of
      multicellular organisms. To investigate the mechanisms which underlie this, we
      have studied the regulation of the model genes Mdc and Il12b, whose stimulus
      induced expression is tightly restricted to specific cells of the immune system.
      Surprisingly, we find that neither the promoter nor the enhancer sequences of
      these genes are sufficient to direct this cell-type specificity. Instead, the
      activities of upstream enhancers are repressed in nonexpressing cells by high
      levels of trimethylated H3K9 in their flanking regions. Genome-wide analysis
      indicates that this manner of regulation is shared by numerous enhancers of cell
      type-specific genes. In dendritic cells and macrophages, the stimulus-induced
      demethylase Jmjd2d controls H3K9me3 levels at these regions, and is thereby
      required for Mdc and Il12b transcription. By experimentally assaying multiple
      enhancers in a variety of cell types, we show that regulation by H3K9me3 is a
      widely used mechanism which imparts specificity to the activities of otherwise
      broadly functional enhancers.

PMID- 22633490
TI  - The Sjogren-Larsson syndrome gene encodes a hexadecenal dehydrogenase of the
      sphingosine 1-phosphate degradation pathway.
AB  - Sphingosine 1-phosphate (S1P) functions not only as a bioactive lipid molecule,
      but also as an important intermediate of the sole sphingolipid-to-glycerolipid
      metabolic pathway. However, the precise reactions and the enzymes involved in
      this pathway remain unresolved. We report here that yeast HFD1 and the Sjogren
      Larsson syndrome (SLS)-causative mammalian gene ALDH3A2 are responsible for
      conversion of the S1P degradation product hexadecenal to hexadecenoic acid. The
      absence of ALDH3A2 in CHO-K1 mutant cells caused abnormal metabolism of
      S1P/hexadecenal to ether-linked glycerolipids. Moreover, we demonstrate that
      yeast Faa1 and Faa4 and mammalian ACSL family members are acyl-CoA synthetases
      involved in the sphingolipid-to-glycerolipid metabolic pathway and that
      hexadecenoic acid accumulates in Deltafaa1 Deltafaa4 mutant cells. These results
      unveil the entire S1P metabolic pathway: S1P is metabolized to glycerolipids via
      hexadecenal, hexadecenoic acid, hexadecenoyl-CoA, and palmitoyl-CoA. From our
      results we propose a possibility that accumulation of the S1P metabolite
      hexadecenal contributes to the pathogenesis of SLS.

PMID- 22633491
TI  - Mapping N-glycosylation sites across seven evolutionarily distant species reveals
      a divergent substrate proteome despite a common core machinery.
AB  - N-linked glycosylation is an important posttranslational modification in all
      eukaryotes, but little is known about the N-glycoproteomes in nonmammalian
      systems. Here, we measure N-glycoproteomes of the major model organisms
      Arabidopsis thaliana, Schizosaccharomyces pombe, Saccharomyces cerevisiae,
      Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio,
      representatively spanning the eukaryotic domain of life. The number of detected N
      glycosylation sites varied between 425 in fission yeast, 516 in budding yeast,
      1,794 in worm, 2,186 in plant, 2,229 in fly, and 2,254 in zebrafish. We find that
      all eukaryotic N-glycoproteomes have invariant characteristics including sequence
      recognition patterns, structural constraints, and subcellular localization.
      However, a surprisingly large percentage of the N-glycoproteome evolved after the
      phylogenetic divergences between plants, fungi, nematodes, insects, and
      vertebrates. Many N-glycosylated proteins coevolved with the rise of
      extracellular processes that are specific within corresponding phylogenetic
      groups and essential for organismal development, body growth, and organ
      formation.

PMID- 22633492
TI  - Evaluation of a clinical decision support algorithm for patient-specific
      childhood immunization.
AB  - OBJECTIVE: To evaluate the effectiveness of a clinical decision support system
      (CDSS) implementing standard childhood immunization guidelines, using real-world
      patient data from the Regenstrief Medical Record System (RMRS). METHODS: Study
      subjects were age 6-years or younger in 2008 and had visited the pediatric clinic
      on the campus of Wishard Memorial Hospital. Immunization records were retrieved
      from the RMRS for 135 randomly selected pediatric patients. We compared vaccine
      recommendations from the CDSS for both eligible and recommended timelines, based
      on the child's date of birth and vaccine history, to recommendations from
      registered nurses who routinely selected vaccines for administration in a busy
      inner city hospital, using the same date of birth and vaccine history. Aggregated
      and stratified agreement and Kappa statistics were reported. The reasons for
      disagreement between suggestions from the CDSS and nurses were also identified.
      RESULTS: For the 135 children, a total of 1215 vaccination suggestions were
      generated by nurses and were compared to the recommendations of the CDSS. The
      overall agreement rates were 81.3% and 90.6% for the eligible and recommended
      timelines, respectively. The overall Kappa values were 0.63 for the eligible
      timeline and 0.80 for the recommended timeline. Common reasons for disagreement
      between the CDSS and nurses were: (1) missed vaccination opportunities by nurses,
      (2) nurses sometimes suggested a vaccination before the minimal age and minimal
      waiting interval, (3) nurses usually did not validate patient immunization
      history, and (4) nurses sometimes gave an extra vaccine dose. CONCLUSION: Our
      childhood immunization CDSS can assist providers in delivering accurate childhood
      vaccinations.

PMID- 22633493
TI  - Prediction of human major histocompatibility complex class II binding peptides: a
      frequent case of publication bias?

PMID- 22633494
TI  - Electrochemical sandwich assay for attomole analysis of DNA and RNA from beer
      spoilage bacteria Lactobacillus brevis.
AB  - Attomole (10(-18)mol) levels of RNA and DNA isolated from beer spoilage bacterial
      cells Lactobacillus brevis have been detected by the electrochemical sandwich DNA
      hybridization assay exploiting enzymatic activity of lipase. DNA sequences
      specific exclusively to L. brevis DNA and RNA were selected and used for probe
      and target DNA design. The assay employs magnetic beads (MB) modified with a
      capture DNA sequence and a reporter DNA probe labeled with the enzyme, both made
      to be highly specific for L. brevis DNA. Lipase-labeled DNAs captured on MBs in
      the sandwich assay were collected on gold electrodes modified with a ferrocene
      (Fc)-terminated SAM formed by aliphatic esters. Lipase hydrolysis of the ester
      bond released a fraction of the Fc redox active groups from the electrode
      surface, decreasing the electrochemical signal from the surface-confined Fc. The
      assay, shown to be efficient for analysis of short synthetic DNA sequences, was
      ineffective with genomic double stranded bacterial DNA, but it allowed down to 16
      amole detection of 1563 nts long RNA, isolated from bacterial ribosomes without
      the need for PCR amplification, and single DNA strands produced from ribosomal
      RNA. No interference from E. coli RNA was registered. The assay allowed analysis
      of 400 L. brevis cells isolated from 1L of beer, which fits the "alarm signal"
      range (from 1 to 100 cells per 100mL).

PMID- 22633495
TI  - Direct aortic access for transcatheter self-expanding aortic bioprosthetic valves
      implantation.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been designed to
      treat elderly patients with severe aortic stenosis at high risk for operation;
      however, these patients are also often affected by severe iliac-femoral
      arteriopathy that prohibits the transfemoral approach. METHODS: From May 2008 to
      January 2012, 400 patients were evaluated for TAVI at our center; of these, 141
      patients (64 men; mean age 81.3+/-8 years) with severe symptomatic aortic
      stenosis and no reasonable surgical option due to excessive risk were eligible
      for CoreValve (137 patients; Medtronic Inc, MN) or Sapien (Edwards Lifesciences,
      CA) implantation. Twenty-five patients (all affected by severe peripheral
      vasculopathy, including five re-do procedures), with a mean The Society of
      Thoracic Surgeons mortality score 11%+/-6%, underwent CoreValve implantation
      directly from the ascending aorta through a right anterior minithoracotomy. This
      case series was reviewed to evaluate the clinical outcomes of these patients. A
      combined team of cardiologists, cardiac surgeons with expertise in hybrid
      procedures, and anesthetists performed all the procedures. RESULTS: In all
      patients after valve deployment, the mean aortic gradient immediately dropped to
      5 mm Hg or less, and the angiographic grade aortic insufficiency was 1 or less in
      22 patients. One patient was converted to the transfemoral approach due to an
      extremely fragile aortic wall, but the patient died of abdominal aorta aneurysm
      rupture on postoperative day 1. Procedural success was obtained in the remaining
      24 patients. A left ventricle tear in 1 patient was successfully surgically
      treated. Four patients required a permanent pacemaker implantation. Thirty-day
      mortality was 8% (2 patients). All discharged patients improved their New York
      Heart Association functional class and functional capacity, and echocardiograms
      demonstrated good valve performance up to 2 years (mean valve gradient, 9 mm Hg).
      During follow-up, 1 patient died of cachexia and another of bone marrow aplasia.
      CONCLUSIONS: TAVI with the direct aortic approach is safe and feasible, offering
      a new attractive option to treat selected high-risk patients with severe aortic
      stenosis and peripheral vasculopathy, including those requiring a re-do
      procedure, and has emerged as a valuable alternative route to transapical access.

PMID- 22633496
TI  - Evaluation of failure to rescue as a quality metric in pediatric heart surgery:
      an analysis of the STS Congenital Heart Surgery Database.
AB  - BACKGROUND: Failure to rescue (FTR; the probability of death after a
      complication) has been adopted as a quality metric in adult cardiac surgery, in
      which it has been shown that high-performing centers with low mortality rates do
      not have fewer complications, but rather lower mortality in those who experience
      a complication (lower FTR). It is unknown whether this holds true in pediatric
      heart surgery. We characterized the relationship between complications, FTR, and
      mortality in this population. METHODS: Children (0 to 18 years) undergoing heart
      surgery at centers participating in the Society of Thoracic Surgeons Congenital
      Heart Surgery Database (2006 to 2009) were included. Outcomes were examined in
      multivariable analysis adjusting for patient characteristics, surgical risk
      category, and within-center clustering. RESULTS: This study included 40,930
      patients from 72 centers. Overall in-hospital mortality was 3.7%, 39.3% had a
      postoperative complication, and the FTR rate (number of deaths in those with a
      complication) was 9.1%. When hospitals were characterized by in-hospital
      mortality rate, there was no difference across hospital mortality tertiles in the
      complication rate in adjusted analysis; however, hospitals in the lowest
      mortality tertile had significantly lower FTR rates (6.6% versus 12.4%;
      p<0.0001). Similar results were seen when evaluating high-severity complications
      and across surgical risk groups. CONCLUSIONS: This analysis suggests that
      hospitals with low mortality rates do not have fewer complications after
      pediatric heart surgery, but instead have lower mortality in those who experience
      a complication (lower FTR). Further investigation into FTR as a quality metric in
      pediatric heart surgery is warranted.

PMID- 22633497
TI  - Total anomalous pulmonary venous connection: factors associated with mortality
      and recurrent pulmonary venous obstruction.
AB  - BACKGROUND: Surgical repair of total anomalous pulmonary venous connection
      (TAPVC) is associated with high rates of mortality and need for reintervention.
      The purpose of this study was to identify variables associated with surgical
      mortality and, in particular, to define predictors of recurrent pulmonary venous
      obstruction. METHODS: All patients who underwent surgical repair for TAPVC from
      2005 to 2010 at a single institution were included in our analysis. Hospital
      course, operative data, and outpatient records were reviewed. RESULTS: Fifty-one
      patients were available for review and all were included in the analysis.
      Anatomic TAPVC subtypes included supracardiac 26 (51%), intracardiac 10 (19.6%),
      infracardiac 9 (17.6%), and mixed 6 (11.8%). Pulmonary venous obstruction was
      present at initial operation in 13 (25.5%) patients. Median age at repair was 18
      days and median weight was 3.6 kg. Single-ventricle physiology was present in 9
      (17.6%), with a diagnosis of heterotaxy syndrome in 7 (13.7%). There were 5
      (9.8%) operative and 2 late deaths. Recurrent pulmonary venous obstruction
      requiring reintervention was found in 8 (15.7%) patients with median time to
      reintervention of 220 days. Obstructed TAPVC was found to be associated with
      surgical mortality (p=0.01). Cardiopulmonary bypass (p=0.02) and aortic cross
      clamp times (p=0.03) were found to be associated with increased risk for
      reintervention. Intraoperative transesophageal echocardiography findings of a
      mean confluence gradient 2 mm Hg or greater was found to be markedly associated
      with recurrent pulmonary venous obstruction requiring reintervention (p<=0.001).
      CONCLUSIONS: Mortality after repair of TAPVC is highest in patients presenting
      with obstruction at time of repair. Longer cardiopulmonary bypass and cross-clamp
      times are associated with recurrent pulmonary venous obstruction requiring
      reintervention. The strongest association with need for reintervention was in
      patients with intraoperative transesophageal echocardiography Doppler evidence of
      pulmonary venous obstruction.

PMID- 22633498
TI  - Endovascular stent-graft repair of aortobronchial fistulas.
AB  - BACKGROUND: Endovascular repair of the descending thoracic aorta has recently
      emerged as a feasible treatment option; however, little is known about its
      application for aortobronchial fistula (ABF). Experience with endovascular repair
      of the thoracic aorta and the outcome of patients with ABFs was reviewed to
      assess whether thoracic endovascular repair is a realistic option. METHODS: From
      February 2001 to May 2011, 386 patients were successfully treated with
      endoluminal grafts to the distal arch or descending thoracic aorta. Among them,
      26 patients with ABF underwent thoracic endovascular repair. These cases were
      reviewed and analyzed retrospectively. Follow-up was 100% complete (mean, 21
      months). RESULTS: The subjects included 26 patients (22 males, 85%; 4 females,
      15%) with a median age of 71 years. Ten patients (38%) were diagnosed with
      atherosclerotic aneurysms, 13 (50%) had pseudoaneurysms associated with prior
      open surgical repair, 1 (4%) had rupture of dissecting aneurysm, and 2 (8%) had
      mycotic aneurysm. There were 4 (15%) in-hospital mortalities, in which the causes
      included bleeding owing to recurrence of hemoptysis (n=3, 11%) and multiple organ
      failure (n=1, 4%). None sustained postoperative stroke or paraplegia. During
      follow-up, ABFs recurred in 4 patients; of these, endograft explantation occurred
      in 3 patients and 1 patient required additional open surgery. No hospital
      mortality resulted among the 4 patients with ABF recurrence. CONCLUSIONS:
      Endovascular management of ABFs appears to be safe and well tolerated with
      minimal risk, even in surgically high-risk patients. Endovascular stent-graft
      repair is likely the first choice for ABF presenting as hemoptysis.

PMID- 22633499
TI  - Needs assessment for an errors-based curriculum on thoracoscopic lobectomy.
AB  - BACKGROUND: Research suggests a benefit from a skills curriculum emphasizing
      error prevention, identification, and management. Our purpose was to identify
      common errors committed by trainees during simulated thoracoscopic lobectomy for
      use in developing an error-based curriculum. METHODS: Twenty-one residents
      (postgraduate years 1 to 8) performed a thoracoscopic left upper lobectomy on a
      previously validated simulator. Videos of the procedure were reviewed in a
      blinded fashion using a checklist listing 66 possible cognitive and technical
      errors. RESULTS: Of the 21 residents, 15 (71%) self-reported completing the
      anatomic lobectomy; however, only 7 (33%) had actually divided all of the
      necessary structures correctly. While dissecting the superior pulmonary vein, 16
      residents (76%) made at least one error. The most common (n=13, 62%) was
      dissecting individual branches rather than the entire vein. On the bronchus, 14
      (67%) made at least one error. Again, the most common (n=9, 43%) was dissecting
      branches. During these tasks, cognitive errors were more common than technical
      errors. While dissecting arterial branches, 18 residents (86%) made at least one
      error. Technical and cognitive errors occurred with equal frequency during
      arterial dissection. The most common arterial error was excess tension on the
      vessel (n=10, 48%). CONCLUSIONS: Curriculum developers should identify skill
      specific technical and judgment errors to verify the scope of errors typically
      committed. For a thoracoscopic lobectomy curriculum, emphasis should be placed on
      correct identification of anatomic landmarks during dissection of the vein and
      airway and on proper tissue handling technique during arterial dissection.

PMID- 22633500
TI  - Pulmonary resection for extensively drug resistant tuberculosis in Kwazulu-Natal,
      South Africa.
AB  - BACKGROUND: Extensively drug resistant tuberculosis (XDR-TB) has been reported in
      58 countries around the world and has emerged as a major public health challenge.
      Our objective was to determine the impact of pulmonary resection on XDR-TB
      treatment outcomes in a resource-constrained setting. METHODS: We conducted a
      retrospective case review of 11 patients with XDR-TB who were referred for
      pulmonary resection between January 2007 and June 2010 at a tertiary care
      referral hospital in South Africa. Two pneumonectomies and three upper
      lobectomies were performed. Occurrence of surgical complications and TB treatment
      outcome were assessed. RESULTS: No perioperative mortality or major morbidity was
      noted. All patients achieved sputum conversion, with 4 regarded as "cured." One
      patient defaulted on treatment, but subsequently returned and is regarded as a
      probable cure. CONCLUSIONS: We describe pulmonary resection for XDR-TB management
      in Africa. Although the initial cohort of XDR-TB patients from Tugela Ferry
      demonstrated nearly complete mortality, our results demonstrate the potential of
      adjuvant surgical methods in XDR-TB treatment. With appropriate chemotherapy and
      timely adjuvant surgery, patients with XDR-TB localized to lobe or lung may
      achieve a "cure" with low morbidity and mortality. Consequently, this approach
      may be the most cost effective treatment for patients suitable for lung
      resection.

PMID- 22633501
TI  - Three-dimensional transesophageal echocardiography for perioperative right
      ventricular assessment.
AB  - BACKGROUND: In high-risk cardiac procedures, dynamic analysis of right
      ventricular (RV) performance is desirable, but the geometric complexity of the RV
      limits the applicability of current two-dimensional echocardiographic imaging
      techniques. This study aimed to evaluate the utility of three-dimensional
      transesophageal echocardiography (TEE) for the perioperative assessment of RV
      function and dimensions. METHODS: Patients undergoing cardiac surgical procedures
      with complete TEE examinations were identified and reviewed according to current
      guidelines to exclude patients with significant coexisting valvular
      regurgitation. Full-volume, three-dimensional datasets were analyzed by two
      independent investigators using stand-alone software, and left ventricular and RV
      dimensions were recorded. RESULTS: Datasets from 50 patients undergoing cardiac
      surgical procedures were evaluated for this study. The mean RV volume was 111.7
      mL (range, 37.5 to 349.7 mL) at end diastole and 67.6 mL (range, 25.5 to 274.4
      mL) at end systole. Intraobserver reliability was 0.93 and 0.90 for end diastolic
      and 0.77 and 0.87 for end systolic volumes. The interobserver reliability for RV
      volumes was 0.83 at end diastole and 0.86 at end systole. The mean stroke volume
      was 43.6 mL (range, 12 to 111.2 mL) for the RV and 49.1 mL (range, 19.9 to 102.8
      mL) for the left ventricle; the correlation coefficient between the two was 0.85.
      CONCLUSIONS: Three-dimensional TEE volumetric measurements were reproducible
      across a wide range of RV dimensions. As postulated by the continuity principle,
      stroke volume measurements between both ventricles correlated well, supporting
      the validity of this approach. Therefore, our work provides preliminary evidence
      that three-dimensional TEE offers reproducible information about RV function and
      size in the dynamic and complex perioperative setting of cardiac surgical
      procedures.

PMID- 22633502
TI  - Recent evidence based advances in neonatology.

PMID- 22633503
TI  - Fluconazole use and safety in the nursery.
AB  - Fluconazole is a triazole antifungal agent that is widely used in the nursery. It
      is available in both intravenous and oral formulation, and is active against most
      of the fungal pathogens that require treatment when retrieved from culture
      samples in neonatal intensive care units. Although clinical use has been wide for
      over 15 years, there have been small safety and efficacy studies completed in
      young infants. Randomised clinical trials assessing effectiveness of this agent
      in prevention of systemic fungal infections in neonates have been published in
      the last decade, and one large additional randomised study has been recently
      completed. Nevertheless, a certain degree of uncertainty still exists regarding
      the kinetics and appropriate dosing of this agent in premature and term infants,
      as well as regarding safety. Areas of poignant debate include the feasibility of
      loading dose strategies, appropriate dosages in the early days of life in the
      different subgroups of preterm infants, and long-term safety of fluconazole
      administered in prophylaxis during the first weeks of life in extremely premature
      infants. This paper reviews the most recent evidence on fluconazole and its role
      in the NICU settings.

PMID- 22633504
TI  - Counselling skills to improve Nursing Relational System within the NICU.
AB  - The relationships amongst healthcare providers, as well as between these and the
      patients/families they care for, are currently experiencing profound changes in
      Italian hospitals, and--more generally--in the whole Italian health system, thus
      reproducing similar changes concomitantly occurring in most Western countries. A
      growing body of evidence suggests that nurses play a central role in the proper
      development of a healthy and transparent communication between caregivers and
      patients/families in all neonatal intensive care units (NICUs). This article
      discusses the current knowledge in this area, and provides further evidence
      supporting the introduction in all NICUs of specific educational and training
      tools for nurses in order to promote the use of counselling skills. The
      implementation of specific counselling skills can improve the Nursing Relational
      System within the NICU, ultimately helping in better addressing the parental
      relational needs in the NICU.

PMID- 22633505
TI  - Neonatal neutropenia: what diagnostic evaluation is needed and when is treatment
      recommended?
AB  - Neutropenia is a relatively frequent finding in the neonatal intensive care unit,
      particularly in very low birth weight neonates during the first week of life.
      Healthy term and preterm neonates have blood neutrophil counts within the same
      basic range as adults, but their neutrophil function, and their neutrophil
      kinetics during infection, differ considerably from those of adults. Neutrophil
      function of neonates, particularly preterm neonates, is less robust than that of
      adults and might also contribute to the increase in propensity to infection. In
      premature infants, early-onset neutropenia is correlated with sepsis, maternal
      hypertension, intrauterine growth restriction, severe asphyxia, and
      periventricular haemorrhage, and might be associated with an increase in the
      incidence of early-onset sepsis, nosocomial infection, and Candida colonisation.
      Some varieties of neutropenia in the NICU are very common and others are
      extremely rare. The most common causes of neutropenia in the NICU have an
      underlying cause that is often evident, and require little diagnostic evaluation.
      Unlike, persistent neutropenia should prompt evaluation even if it is of moderate
      severity. The laboratory tests to consider are those that provide a specific
      diagnosis. The first tests that should be ordered are a blood film, a complete
      blood count on the mother, and, if her blood neutrophil concentration is normal,
      maternal neutrophil antigen typing and an anti-neutrophil antibody screen. A bone
      marrow biopsy can be useful in cases with prolonged, unusual, or refractory
      neutropenia. Various treatments have been proposed as means of enhancing
      neutrophil production and function in preterm infants. Both recombinant
      granulocyte stimulating factor and recombinant granulocyte macrophage-colony
      stimulating factor have been tried with variable success. Intravenous
      immunoglobulin, corticosteroids, granulocyte transfusions, and gamma interferon
      did not show a clear adequate beneficial role for the therapy of neonatal
      neutropenia.

PMID- 22633506
TI  - Is it worthwhile using a transcutaneous bilirubinometer in the nursery?
AB  - Jaundice is a potential threat to neonatal health and/or life. The advantages and
      limitations of transcutaneous determination of bilirubin concentration and
      current devices are briefly discussed in this paper.

PMID- 22633507
TI  - What is BPD in 2012 and what will BPD become?

PMID- 22633508
TI  - Nurse role in RSV management.

PMID- 22633509
TI  - Neuroimaging in CMV congenital infected neonates: how and when.
AB  - Neonatal congenital infections are an important cause of mortality, morbidity and
      long-term neurodevelopmental and sensorineural sequelae. Many pathogens can cause
      in utero infection, and among them, cytomegalovirus (CMV) plays a prominent role.
      In developed countries, CMV poses major health problems as it is the most common
      pathogen leading to congenital infection, and the leading cause of nonhereditary
      deafness in children. Evaluation of central nervous system (CNS) involvement in
      congenital CMV infected newborns is mandatory to better assess the severity of
      the disease, to guide adequate treatment, to define prognosis, and to tailor
      follow-up observations and parents' counselling. Cerebral ultrasonography (cUS),
      Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) are the currently
      available techniques to evaluate infants with suspected or proven congenital CMV
      infection. In congenital CMV infection, their role in early detection and
      confirmation of cerebral involvement within the first month of life is crucial to
      initiate specific treatment with antivirals. Neonatologists, paediatricians and
      radiologists should be aware of the role, the limitations and the inherent risks
      related to the use of these specific neuroimaging diagnostic tools in these
      infants. In this article we will discuss from a neonatological perspective the
      advantages, disadvantages, risks and limitations of each imaging technique.

PMID- 22633510
TI  - Methods of enteral feeding in preterm infants.
AB  - Whenever possible, oral feeding is the preferred method in neonatal feeding.
      However, many premature infants are unable to suck and swallow effectively; in
      these cases alternative methods of nutrient delivery must be used. We briefly
      review the different feeding methods used in neonatal units, with particular
      attention to their theoretical advantages, disadvantages and to the current best
      evidence available.

PMID- 22633511
TI  - High risk for RSV bronchiolitis in late preterms and selected infants affected by
      rare disorders: a dilemma of specific prevention.
AB  - Respiratory syncytial virus (RSV) is the most frequent aetiologic agent that
      causes bronchiolitis and lower respiratory tract infection in infants. These
      infections may be severe and even life-threatening in selected high-risk
      populations. Traditional, well-established, high-risk populations are preterm
      infants with or without chronic lung disease and children with congenital heart
      disease. For these children, RSV prophylaxis using palivizumab, a monoclonal anti
      RSV humanised antibody against the F-protein of RSV, has proven safe and
      efficacious in preventing RSV-related hospitalisation. Recently, a number of rare
      medical conditions have been associated with the risk of severe RSV infections.
      Evidence of safety and efficacy of RSV prophylaxis in these populations is
      lacking. Given the low incidence of these conditions, randomised trials are not
      feasible. A practical, opinion-based approach to this dilemma is offered in this
      paper. It is proposed that these rare disorders may qualify for RSV prophylaxis
      if the association between a specific condition and the risk of severe RSV
      infection is confirmed in at least 3 independent publications, of which at least
      1 includes a prospective cohort study. To facilitate pharmaco-economic analyses,
      at least one of the three studies must also report on the absolute risk of severe
      RSV infection in the specified illness. The authors believe that qualification
      criteria will enable caregivers to target RSV prophylaxis more effectively in
      children with rare conditions and the proposed approach provides direction for
      future epidemiological studies on the risk of severe RSV infection in children
      with these uncommon, medical illnesses.

PMID- 22633512
TI  - What is RDS in 2012?

PMID- 22633513
TI  - "Getting to Zero": preventing invasive Candida infections and eliminating
      infection-related mortality and morbidity in extremely preterm infants.
AB  - Prevention of invasive Candida infections (ICI) is an achievable goal for every
      NICU and supported by A-1 evidence. Due to the incidence of ICI, high infection
      associated mortality and neurodevelopmental impairment, antifungal prophylaxis
      should be targeted to infants <1000 g or <= 27 weeks gestation. There is A-1
      evidence for both fluconazole and nystatin prophylaxis for the prevention of ICI.
      Evidence currently would favour fluconazole prophylaxis in high-risk preterm
      infants since intravenous fluconazole prophylaxis has greater efficacy compared
      to enteral nystatin prophylaxis, efficacy in the most immature patients in whom
      mortality is the highest, requires less dosing, and can be given to infants with
      gastrointestinal disease or haemodynamic instability. All NICUs caring for
      extremely preterm infants should use antifungal prophylaxis. Even in NICUs with
      low rates of ICI, antifungal prophylaxis is crucial to improving survival and
      neurodevelopmental outcomes for this vulnerable population. For infants 1000-1500
      g if there is concern for ICI in the NICU, either drug could be chosen for
      prophylaxis. Fluconazole prophylaxis administered at 3 mg/kg twice a week, while
      intravenous access is required, appears to be the safest and most effective
      schedule in preventing ICI while attenuating the emergence of fungal resistance.
      Invasive Candida infections are one group of infections we can prevent.

PMID- 22633514
TI  - Drug accountability and drug administration safety controls in the NICU.

PMID- 22633515
TI  - Neonatology in the emerging countries: the strategies and health-economics
      challenges related to prevention of neonatal and infant infections.
AB  - The prevalence of neonatal and infant infections is higher in emerging countries
      when compared to the developed world. Major factors associated to this increased
      frequency include the scarcity of trained health personnel, overcrowding of the
      neonatal units, late onset and slow advance of feeding, use of formula instead of
      breastfeeding, failure to comply with handwashing recommendations, and excessive
      use of antibiotics, resulting in the emergence of resistant strains. Infants
      discharged home frequently share rooms with a large number of siblings and other
      cohabitants, increasing the risk of infection by respiratory viruses. Several
      strategies are described that could decrease these serious problems which impact
      increasing significantly neonatal and infant mortality rates in developing
      countries.

PMID- 22633516
TI  - Neonatal fungal infections: when to treat?
AB  - Candida infections are a major cause of morbidity and mortality in neonatal
      intensive care units. Mortality following Candida bloodstream infections is as
      high as 40%, and neurodevelopmental impairment is common among survivors. Because
      invasive fungal infections are common and extremely difficult to diagnose,
      empirical treatment with antifungal therapy should be considered in high-risk,
      low-birth-weight infants who fail to quickly respond to empirical antibacterial
      treatment. Risk factors to consider when deciding to administer empirical
      antifungal therapy include: prior exposure to third-generation cephalosporins,
      extreme prematurity, and presence of central venous catheters.

PMID- 22633517
TI  - Clinical characteristics and response to prophylactic fluconazole of preterm VLBW
      neonates with baseline and acquired fungal colonisation in NICU: data from a
      multicentre RCT.
AB  - BACKGROUND: Fungal colonisation by Candida spp. affects a high proportion of VLBW
      neonates in NICU. However, few data are available on the clinical characteristics
      of colonisation in preterm infants who are colonised at baseline via vertical
      transmission, compared to preterms who become colonised during their stay in NICU
      via horizontal transmission. MATERIAL AND METHODS: We reviewed the database of a
      multicentre, randomised trial of prophylactic fluconazole in VLBW neonates
      conducted in 8 Italian NICUs in the years 2004 and 2005 (Manzoni et al., NEJM
      2007;356(24):2483-95). Per the protocol, all enrolled infants underwent weekly
      surveillance cultures from birth till discharge. We investigated the frequency of
      the two different modalities of Candida colonisation in this population, as well
      as the clinical and outcome characteristics possibly related to them. RESULTS:
      Overall, Candida colonisation affected 54 of 336 infants (16.1%). Baseline (i.e.,
      detected <3(rd) day of life) colonisation affected 16 (4.7%), and acquired 38
      (11.4%), of the 54 colonised preterms. Infants with baseline colonisation had
      significantly higher birth weight (1229 +/- 28 g vs. 1047 g +/- 29, p = 0.01) and
      gestational age (30.2 wks +/- 2.7 vs. 28.5 wks +/- 2.6, p = 0.01), and were
      significantly more likely to limit progression from colonisation to invasive
      Candida infection when fluconazole prophylaxis was instituted (21.6% vs. 42.7%, p
      = 0.009). Isolation of C. parapsilosis was significantly more frequent in infants
      with acquired colonisation. CONCLUSIONS: Infants with baseline and acquired
      colonisation differ for demographics characteristics and for their response to
      fluconazole prophylaxis. This information may be useful for targeting more
      accurate management strategies for these two different groups of colonised
      preterms in NICU.

PMID- 22633518
TI  - Neonatal cutaneous disseminated aspergillosis in a preterm extremely-low-birth
      weight infant with favourable outcome at 3-year follow-up: a case report.
AB  - Invasive disseminated neonatal aspergillosis is an uncommon disease, with only
      scattered reports in literature in the last few years. Here we report on a 25
      week gestational age, 730 g at birth preterm female infant who developed on day
      of-life 10 multiple cutaneous exhulcerative lesions in her right arm, trunk and
      abdomen. Early recognition and diagnosis of these lesions as a due to cutaneous
      initial symptom of cutaneous disseminated aspergillosis, as well as prompt
      treatment with Liposomal amphotericin B + Itraconazole, secured successful
      recovery from the systemic infection. Skin lesions healed without any surgical
      treatment. The infant was discharged in good health. Long-term follow-up at three
      years of age revealed normality of all neurodevelopmental and cognitive
      parameters. To our knowledge, this is one of the very few cases of survival, free
      from sequelae, for a preterm infant affected by neonatal cutaneous disseminated
      aspergillosis.

PMID- 22633519
TI  - Early and late onset sepsis in very-low-birth-weight infants from a large group
      of neonatal intensive care units.
AB  - BACKGROUND: Very-low-birth-weight (VLBW, <1500 g birth weight) infants are at
      high risk for both early- and late-onset sepsis. Prior studies have observed a
      predominance of Gram-negative organisms as a cause of early-onset sepsis and Gram
      positive organisms as a cause of late-onset sepsis. These reports are limited to
      large, academic neonatal intensive care units (NICUs) and may not reflect
      findings in other units. The purpose of this study was to determine the risk
      factors for sepsis, the causative organisms, and mortality following infection in
      a large and diverse sample of NICUs. METHODS: We analysed the results of all
      cultures obtained from VLBW infants admitted to 313 NICUs from 1997 to 2010.
      RESULTS: Over 108,000 VLBW infants were admitted during the study period. Early
      onset sepsis occurred in 1032 infants, and late-onset sepsis occurred in 12,204
      infants. Gram-negative organisms were the most commonly isolated pathogens in
      early-onset sepsis, and Gram-positive organisms were most commonly isolated in
      late-onset sepsis. Early- and late-onset sepsis were associated with increased
      risk of death controlling for other confounders (odds ratio 1.45 [95% confidence
      interval [CI] 1.21,1.73], and OR 1.30 [95%CI 1.21, 1.40], respectively).
      CONCLUSIONS: This is the largest report of sepsis in VLBW infants to date.
      Incidence for early-onset sepsis and late-onset sepsis has changed little over
      this 14-year period, and overall mortality in VLBW infants with early- and late
      onset sepsis is higher than in infants with negative cultures.

PMID- 22633520
TI  - Stem cells for bronchopulmonary dysplasia and intraventricular haemorrhage repair
      in preterm infants.

PMID- 22633521
TI  - Too much or too little: how to handle oxygen saturation in the neonatal intensive
      care unit.

PMID- 22633522
TI  - Gentle ventilation: the new evidence from the SUPPORT, COIN, VON, CURPAP,
      Colombian Network, and Neocosur Network trials.
AB  - Many neonates have respiratory disorders requiring oxygen supplementation and
      respiratory support. Even though advances in respiratory care such as surfactant
      and new ventilatory techniques have improved outcomes, mortality from respiratory
      failure and morbidities such as bronchopulmonary dysplasia are still common. In
      the trials of prophylactic, early, or late surfactant, the control infants
      received mechanical ventilation. It is possible that the control infants had lung
      injury secondary to mechanical ventilation. This review will address the recent
      trials of early continuous positive airway pressure (CPAP) as an alternative to
      the common practice of surfactant and mechanical ventilation.

PMID- 22633523
TI  - Neonates born to mothers using antidepressant drugs.

PMID- 22633524
TI  - Liposomal amphotericin B does not induce nephrotoxicity or renal function
      impairment in premature neonates.
AB  - BACKGROUND: Liposomal amphotericin B (LAMB) is frequently administered in NICU to
      preterm infants <1500 g at birth (VLBW) for treatment of systemic fungal
      infections (SFI). Concerns exist on safety and tolerability of such drug in
      patients who are at risk for renal function impairment due to their prematurity.
      AIM: To assess the occurrence of renal function impairment related to LAMB in a
      10-year cohort of VLBW neonates treated with this drug. METHODS: Through database
      search of clinical charts, all VLBW neonates admitted to a 3(rd) level NICU in
      the years 1998-2007 and undergoing treatment with LAMB were identified. The
      occurrence of LAMB-attributable renal toxicity was investigated; infants
      withdrawn from treatment for development of adverse effects or toxicity were
      identified. RESULTS: In the study period, 71 of 792 admitted VLBW neonates (8.9%)
      underwent antifungal treatment with LAMB administered at the recommended dosages
      (3-to-5 mg/kg/day). Mean duration of treatment was 14 (+/-9) days, mean
      cumulative dose given was 58 (+/-25) mg/kg per infant. Renal compromise, defined
      as hypokalaemia, and/or elevated creatinine serum levels, and/or decreased urine
      output, occurred in 2 of 71 (2.8%) treated patients, by 5 (+/-3) mean days after
      treatment initiation. In both patients LAMB was withdrawn; renal function
      impairment was only mild and transient, and normal renal function was restored at
      discharge. No other significant adverse effects were recorded in any treated
      neonate. CONCLUSIONS: LAMB is generally safe and well tolerated in VLBW neonates.
      The occurrence of LAMB-related nephrotoxicity appears to be uncommon, mild and
      transient.

PMID- 22633526
TI  - Correct choices for correct treatments: key issues in the management of Candida
      infections in preterm neonates.
AB  - Invasive Candida infections (ICI) have a high burden of morbidity and mortality
      in the neonatal setting. Although the identification of effective prophylactic
      strategies has recently led to the prevention of many episodes of systemic fungal
      disease, the identification of effective treatment strategies is still a
      priority. The correct choice of the most appropriate antifungal drug for
      treatment of such infections requires specific expertise, as well as careful
      consideration of a number of variables related both to the characteristics of the
      patient and to the peculiarities of these infections in neonates. The ideal
      antifungal drug for preterm neonates should have a good ability to target fungal
      biofilms, in order to prevent or improve the course of end-organ localisations.
      It should also be active against fluconazole-resistant species, as well as safe
      enough to be used with no or limited interference with other neonatal drugs. In
      this view, the echinocandin class of antifungal agents has recently proven to be
      a suitable option for treatment. However, further studies are warranted to better
      establish kinetics and appropriate dosing of these agents in premature and term
      infants, as well as their ability to improve late outcomes of ICI.

PMID- 22633525
TI  - Sepsis in young infants with congenital heart disease.
AB  - BACKGROUND: We sought to describe the incidence, pathogen distribution, and
      mortality associated with blood culture-proven sepsis in young infants with
      congenital heart disease (CHD) admitted to a neonatal intensive care unit (NICU).
      METHODS: Cohort study of all blood cultures obtained from infants with CHD
      between 4 and 120 days of age cared for in 250 NICUs managed by the Pediatrix
      Medical Group in the United States between 1996 and 2007. RESULTS: Of 11,638
      infants with CHD, 656 (6%) had 821 episodes of sepsis: a cumulative incidence of
      71/1000 admissions. Gram-positive organisms were the most common cause (64%), and
      coagulase-negative Staphylococcus and Staphylococcus aureus were the most
      frequently isolated species. On multivariable regression, infants with sepsis
      were more likely to die compared to infants with sterile blood cultures (odds
      ratio [OR] = 1.53 [95% confidence interval: 1.09, 2.13]). Infants with Gram
      negative bacteraemia and candidaemia were more likely to die than infants with
      sterile blood cultures (OR = 2.01 [1.20, 3.37], and OR = 3.18 [1.60, 6.34],
      respectively). CONCLUSION: Infants with CHD have a high incidence of culture
      proven sepsis, especially with staphylococcal organisms. Gram-negative
      bacteraemia and candidaemia are strongly associated with increased mortality in
      this group of young infants.

PMID- 22633527
TI  - Altered default network resting state functional connectivity in patients with a
      first episode of psychosis.
AB  - BACKGROUND: Default network (DN) abnormalities have been identified in patients
      with chronic schizophrenia using "resting state" functional magnetic resonance
      imaging (R-fMRI). Here, we examined the integrity of the DN in patients
      experiencing their first episode of psychosis (FEP) compared with sex- and age
      matched healthy controls. METHODS: We collected R-fMRI data from 19 FEP patients
      (mean age 24.9 +/- 4.8 yrs, 14 males) and 19 healthy controls (26.1 +/- 4.8 yrs,
      14 males) at 3T. Following standard preprocessing, we examined the functional
      connectivity (FC) of two DN subsystems and the two DN hubs (P<0.0045, corrected).
      RESULTS: Patients with FEP exhibited abnormal FC that appeared largely restricted
      to the dorsomedial prefrontal cortex (dMPFC) DN subsystem. Relative to controls,
      FEP patients exhibited weaker positive FC between dMPFC and posterior cingulate
      cortex (PCC) and precuneus, extending laterally through the parietal lobe to the
      posterior angular gyrus. Patients with FEP exhibited weaker negative FC between
      the lateral temporal cortex and the intracalcarine cortex, bilaterally. The PCC
      and temporo-parietal junction also exhibited weaker negative FC with the right
      fusiform gyrus extending to the lingual gyrus and lateral occipital cortex, in
      FEP patients, compared to controls. By contrast, patients with FEP showed
      stronger negative FC between the temporal pole and medial motor cortex, anterior
      precuneus and posterior mid-cingulate cortex. CONCLUSIONS: Abnormalities in the
      dMPFC DN subsystem in patients with a FEP suggest that FC patterns are altered
      even in the early stages of psychosis.

PMID- 22633528
TI  - Whole brain resting state functional connectivity abnormalities in schizophrenia.
AB  - BACKGROUND: Schizophrenia has been associated with disturbances in brain
      connectivity; however the exact nature of these disturbances is not fully
      understood. Measuring temporal correlations between the functional MRI time
      courses of spatially disparate brain regions obtained during rest has recently
      emerged as a popular paradigm for estimating brain connectivity. Previous resting
      state studies in schizophrenia explored connections related to particular
      clinical or cognitive symptoms (connectivity within a-priori selected networks),
      or connections restricted to functional networks obtained from resting state
      analysis. Relatively little has been done to understand global brain connectivity
      in schizophrenia. METHODS: Eighteen patients with chronic schizophrenia and 18
      healthy volunteers underwent a resting state fMRI scan on a 3T magnet. Whole
      brain temporal correlations have been estimated using resting-state fMRI data and
      free surfer cortical parcellations. A multivariate classification method was then
      used to indentify brain connections that distinguish schizophrenia patients from
      healthy controls. RESULTS: The classification procedure achieved a prediction
      accuracy of 75% in differentiating between groups on the basis of their
      functional connectivity. Relative to controls, schizophrenia patients exhibited
      co-existing patterns of increased connectivity between parietal and frontal
      regions, and decreased connectivity between parietal and temporal regions, and
      between the temporal cortices bilaterally. The decreased parieto-temporal
      connectivity was associated with the severity of patients' positive symptoms,
      while increased fronto-parietal connectivity was associated with patients'
      negative and general symptoms. DISCUSSION: Our analysis revealed two co-existing
      patterns of functional connectivity abnormalities in schizophrenia, each related
      to different clinical profiles. Such results provide further evidence that
      abnormalities in brain connectivity, characteristic of schizophrenia, are
      directly related to the clinical features of the disorder.

PMID- 22633529
TI  - Apolipoprotein E epsilon4 and age effects on florbetapir positron emission
      tomography in healthy aging and Alzheimer disease.
AB  - OBJECTIVES: Investigate apolipoprotein E epsilon4 (APOE4) gene and aging effects
      on florbetapir F18 positron emission tomography (PET) in normal aging and
      Alzheimer's disease (AD). METHODS: Florbetapir F18 PET images were analyzed from
      245 participants, 18-92 years of age, from Avid Radiopharmaceutical's multicenter
      registered trials, including 86 younger healthy control volunteers (yHC), 61
      older healthy control volunteers (oHC), 53 mild cognitive impairment (MCI)
      patients, and 45 AD dementia patients (DAT). Mean florbetapir standard uptake
      value ratios (SUVRs) were used to evaluate the effects of APOE4 carrier status,
      older age, and their interaction in each of these groups. RESULTS: In comparison
      with non-carriers, the APOE4 carriers in each of the oHC, MCI, and DAT groups had
      higher mean cortical-to-cerebellar florbetapir SUVRs, patterns of florbetapir PET
      elevations characteristic of DAT, and a higher proportion meeting florbetapir PET
      positivity criteria. Only the oHC group had a significant association between
      mean cortical florbetapir SUVRs and age. In cognitively normal adults, without
      regards to APOE4 genotype, amyloid began to increase at age 58 (95% confidence
      interval [CI]: 52.3-63.7), with a predicted typical age of florbetapir positivity
      occurring around age 71 years. Presence of the APOE4 gene reduced the age of
      predicted florbetapir positivity in normal aging to around age 56 years,
      approximately 20 years younger than non-carriers. INTERPRETATION: Cerebral
      amyloid deposition is associated with APOE4 carrier status in older healthy
      control subjects and symptomatic AD patients, and increases with age in older
      cognitively normal individuals. Amyloid imaging positivity appears to begin near
      age 56 years in cognitively intact APOE4 carriers and age 76 years in APOE4 non
      carriers.

PMID- 22633530
TI  - Molecular modeling predicts structural changes in the A subunit of factor XIII
      caused by two novel mutations identified in a neonate with severe congenital
      factor XIII deficiency.
AB  - INTRODUCTION: Coagulation factor XIII (FXIII) is a fibrin-stabilizing factor,
      which contributes to hemostasis, wound healing, and maintenance of pregnancy.
      Accordingly, patients with congenital FXIII deficiency manifest a life-long
      bleeding tendency, abnormal wound healing and recurrent miscarriage. In order to
      understand the molecular mechanisms of congenital FXIII deficiency, genetic
      analysis and molecular modeling were carried out in a Japanese male neonate with
      severe FXIII deficiency. METHODS AND RESULTS: Two novel mutations, Y204Stop (or
      Y204X, TAT to TAA) and S708R (AGC to AGG), were heterozygously identified by
      nucleotide sequencing analysis in exons V and XV of the gene for the A subunit of
      FXIII (FXIII-A). Y204X and S708R would lead to nonsense mediated mRNA decay and
      misfolding of the FXIII-A molecule, respectively. Using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis, the presence of
      these mutations was confirmed both together in the proband and one each
      separately in either the maternal or paternal sides of his family. In addition,
      moderately decreased FXIII activity was associated with the presence of either
      mutation. Molecular modeling predicted that the mutant molecule of S708R would be
      structurally compromised by the substitution of the Ser with the larger extended
      bulky and positively charged Arg side-chain. CONCLUSION: It is probable that the
      impaired tertiary structure of the mutant S708R molecule leads to its
      instability, which is at least in part responsible for the FXIII deficiency of
      this patient. This is consistent with the fact that the mutations and the reduced
      FXIII activities co-segregate among the patient's family members.

PMID- 22633531
TI  - The F11 rs2289252 polymorphism is associated with FXI activity levels and APTT
      ratio in women with thrombosis.

PMID- 22633532
TI  - The effects of pneumatic tube system transport on ROTEM analysis and contact
      activation assessed by thrombin generation test.
AB  - Thromboelastometry (ROTEM) is a popular point-of-care test. It generates results
      quickly and may benefit individualised guided haemostatic therapy. However,
      processing of specimens by non-technicians might decrease the quality and
      reproducibility of results. Centralised laboratory equipment receiving specimens
      through a pneumatic tube system (PTS) could avoid this. This study aimed to
      evaluate the influence of PTS transport on ROTEM results and its contribution to
      contact activation assessed by thrombin generation (TG). METHODS: Specimens from
      44 patients were drawn immediately after arterial puncture. Two were
      anticoagulated by citrate and two by citrate/corn trypsin inhibitor, a Factor
      XIIa pathway inhibitor. Both types of samples were transported by walking and
      PTS. Subsequently, analysis was performed: ROTEM on citrated blood, and TG on
      citrated and corn trypsin inhibitor (CTI) blood using either 0 or 1 pM tissue
      factor (TF). RESULTS: In ROTEM analysis the NATEM assay showed significant
      differences. The EXTEM assay revealed small significant differences for clot
      formation time: 65 seconds (SD +/- 20) versus 67 seconds (SD +/- 17), and alpha
      angle 79 degrees  (SD +/- 3) versus 77 degrees  (SD +/- 3). The results remained
      within reference range. TG was not significantly affected by the type of tube
      transport, independent of the amount of TF. CONCLUSION: PTS for ROTEM analysis is
      feasible except for NATEM assays. The amount of contact activation via Factor
      XIIa in terms of TG is independent of transport type. However, due to the
      different characteristics of pneumatic systems, hospitals should check its impact
      on the results before introducing this route of transport.

PMID- 22633533
TI  - Associations between salivary testosterone and cortisol levels and neonatal
      health and growth outcomes.
AB  - OBJECTIVES: Male vulnerability in health and growth outcomes has often been
      reported in very low birth weight (VLBW) preterm neonates. On the basis of gender
      difference theories, possible associations were explored between the levels of
      postnatal salivary testosterone/cortisol and the outcomes of neonatal
      health/growth. METHODS: This study used an exploratory and comparative research
      design. One-hundred-one mother-VLBW preterm neonate pairs were recruited from the
      neonatal intensive care unit (NICU) of a tertiary medical center in the
      Southeastern, US. Demographic information, health and growth variables of
      neonates, and pregnancy and labor variables of mothers were obtained from the
      medical record reviews and interviews of mothers. Saliva samples from each pair
      were collected between 9 and 60 days of age. The levels of testosterone and
      cortisol were determined by using an enzyme immunoassay methodology. RESULTS:
      Linear regression analysis showed that neonatal health problems were positively
      associated with the levels of postnatal salivary testosterone and cortisol, while
      growth delays were positively associated with the levels of postnatal salivary
      testosterone after adjusting for the characteristics of neonates and mothers and
      day of saliva sampling. The salivary levels of testosterone and cortisol were
      higher in neonates than in mothers. A positive correlation between the levels of
      testosterone and cortisol was found in neonates and in mothers. CONCLUSIONS: The
      level of postnatal salivary testosterone is a more reliable marker in assessing
      neonatal health and growth outcomes compared to salivary cortisol. Further
      research on both testosterone and cortisol measurements at various stages during
      the neonatal period may elucidate further these associations.

PMID- 22633534
TI  - Relationship between glutamate, GOT and GPT levels in maternal and fetal blood: a
      potential mechanism for fetal neuroprotection.
AB  - BACKGROUND: Excess glutamate in the brain is thought to be implicated in the
      pathophysiology of fetal anoxic brain injury, yet little is known about the
      mechanisms by which glutamate is regulated in the fetal brain. This study
      examines whether there are differences between maternal and fetal glutamate
      concentrations, and whether a correlation between them exists. METHODS: 10 ml of
      venous blood was extracted from 87 full-term (>37 weeks gestation) pregnant women
      in active labor. Immediately after delivery of the neonate, 10 ml of blood from
      the umbilical artery and vein was extracted. Samples were analyzed for levels of
      glutamate, glutamate-oxaloacetate transaminase (GOT), and glutamate pyruvate
      transaminase (GPT). RESULTS: Fetal blood glutamate concentrations in both the
      umbilical artery and vein were found to be significantly higher than maternal
      blood (p<0.001). Similarly, fetal serum GOT levels in the umbilical artery and
      vein were found to be significantly higher than maternal GOT levels (p<0.001).
      The difference in GPT levels between maternal and fetal serum was not
      statistically significant. There was no difference in fetal glutamate, GOT or GPT
      between the umbilical artery and vein. There was an association observed between
      glutamate levels in maternal blood and glutamate levels in both venous (R=0.32,
      p<0.01) and arterial (R=0.33, p<0.05) fetal blood. CONCLUSIONS: This study
      demonstrated that higher baseline concentrations of blood glutamate are present
      in fetal blood compared with maternal blood, and this was associated with
      elevated GOT, but not GPT levels. An association was observed between maternal
      and fetal blood glutamate levels.

PMID- 22633535
TI  - Development of antimicrobial films for microbiological control of packaged salad.
AB  - The aim of the present work was to characterize the antimicrobial efficiency of
      films consisting of PP/EVOH structures with oregano essential oil and citral.
      Both substances are known for their antimicrobial activity based on their
      interaction with the cell membrane. The films developed were used to pack
      minimally processed salads, combining modified atmosphere technology to extend
      shelf-life and active packaging technology to reduce possible microbiological
      risks. The antimicrobial activity of the films against the pathogenic
      microorganisms Escherichia coli, Salmonella enterica and Listeria monocytogenes
      and natural microflora was investigated "in vitro" and also on the food itself.
      The effect of release of the antimicrobial agent on the sensory characteristics
      of the salad was also studied. The results showed that antimicrobial activity
      reduced spoilage flora on the salad as well as inhibited the growth of pathogens
      in contaminated salads. This effect was greater against Gram-negative bacteria.
      Sensory studies showed that the package that was most effective and most accepted
      by customers was the one containing 5% oregano essential oil.

PMID- 22633536
TI  - Evaluation of Lactobacillus rhamnosus GG and Lactobacillus acidophilus NCFM
      encapsulated using a novel impinging aerosol method in fruit food products.
AB  - This study investigated the effect of microencapsulation on the survival of
      Lactobacillus rhamnosus GG and Lactobacillus acidophilus NCFM and their
      acidification in orange juice at 25 degrees C for nine days and at 4 degrees C
      over thirty five days of storage. Alginate micro beads (10-40 MUm) containing the
      probiotics were produced by a novel dual aerosol method of alginate and CaCl(2)
      cross linking solution. Unencapsulated L. rhamnosus GG was found to have
      excellent survivability in orange juice at both temperatures. However
      unencapsulated L. acidophilus NCFM showed significant reduction in viability.
      Encapsulation of these two bacteria did not significantly enhance survivability
      but did reduce acidification at 25 degrees C and 4 degrees C. In agreement with
      this, encapsulation of L. rhamnosus GG also reduced acidification in pear and
      peach fruit-based foods at 25 degrees C, however at 4 degrees C difference in pH
      was insignificant between free and encapsulated cells. In conclusion, L.
      rhamnosus GG showed excellent survival in orange juice and microencapsulation has
      potential in reducing acidification and possible negative sensory effects of
      probiotics in orange juice and other fruit-based products.

PMID- 22633537
TI  - Peptide nucleic acid fluorescence in situ hybridization for identification of
      Listeria genus, Listeria monocytogenes and Listeria ivanovii.
AB  - A fluorescent in situ hybridization (FISH) method in conjunction with fluorescin
      labeled peptide nucleic acid (PNA) probes (PNA-FISH) for detection of Listeria
      species was developed. In silico analysis showed that three PNA probes Lis-16S-1,
      Lm-16S-2 and Liv-16S-5 were suitable for specific identification of Listeria
      genus, Listeria monocytogenes and Listeria ivanovii, respectively. These probes
      were experimentally verified by their reactivity against 19 strains of six
      Listeria species (excluding newly described species Listeria marthii and Listeria
      rocourtiae) and eight other bacterial species. The PNA-FISH method was optimized
      as 30 min of hybridization with 0.2% Triton X-100 in the solution and used to
      identify 85 Listeria strains from individual putative Listeria colonies on PALCAM
      agar plates streaked from selectively enriched cultures of 780 food or food
      related samples. Of the 85 Listeria strains, thirty-seven were identified as L.
      monocytogenes with the probe Lm-16S-2 and two as L. ivanovii with the probe Liv
      16S-5 which was in agreement with the results obtained by the API LISTERIA
      method. Thus, the PNA-FISH protocol has the potential for identification of
      pathogenic Listeria spp. from food or food-related samples.

PMID- 22633538
TI  - The effect of marriage on utilization of colorectal endoscopy exam in the United
      States.
AB  - PURPOSE: This study examines the association between marriage and colorectal
      endoscopy exam, and whether this association varies by gender and financial
      benefits of marriage including improved access to health insurance and pooled
      family income. METHODS: Representative survey data of the non-institutionalized
      United States population were used from the 2000, 2005, and 2008 National Health
      Interview Survey. Analyses targeted persons 50-85 years of age without a personal
      history of cancer and with complete information on all study variables
      (n=21,760). Multivariate logistic regression was used to model marital status
      differences in the probability of undergoing a colorectal endoscopy exam with
      interaction effects used to model variation over time by gender, health
      insurance, and poverty level. RESULTS: Married persons were more likely than
      unmarried persons to report ever having undergone a colorectal endoscopy exam
      (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.12-1.29), and the
      difference between married and unmarried persons in the probability of undergoing
      a colorectal endoscopy exam remained stable over time. Married persons were more
      likely than unmarried persons to report having undergone a colorectal endoscopy
      exam within the past 10 years (OR, 1.49; 95% CI, 1.15-1.95). For each survey
      year, married men were significantly more likely than women and unmarried men to
      report having undergone a colorectal endoscopy exam. For example, in 2008, 56% of
      married men reported having undergone a colorectal endoscopy exam, compared to
      49% of unmarried men, 52% of married women, and 50% of unmarried women. Among
      persons with health insurance, married persons were significantly more likely
      than unmarried persons to have undergone a colorectal endoscopy exam. Among
      persons who were poor, there was no difference by marital status in the
      likelihood of having undergone a colorectal endoscopy exam. However, among
      persons who were not poor, married persons were more likely than unmarried
      persons to have undergone a colorectal endoscopy exam. CONCLUSION: Given that
      colorectal endoscopy exams are a potentially life-saving procedure, persistently
      higher uptake of colorectal endoscopy for married persons over time may be an
      important health promoting benefit of marriage. Therefore, clinicians and policy
      makers should focus on improving the use of cancer prevention services among
      unmarried persons.

PMID- 22633540
TI  - Use of the photoelastic method and finite element analysis in the assessment of
      wall strain in abdominal aortic aneurysm models.
AB  - Abdominal aortic aneurysm (AAA) is a significant health problem. Current clinical
      rupture-risk relies primarily on the maximum diameter of the AAA and also growth
      rate. However, AAAs are a patient-specific problem and recently, numerical tools
      have been employed to estimate rupture-potential. Alternatively, experimental
      assessment of AAA biomechanics receives less attention, yet, rigorous validation
      of numerical tools is required prior to clinical acceptance. This paper examines
      the use of the photoelastic method to assess wall strain and its validation using
      finite element analysis (FEA) in a small number of patient-specific AAA models.
      Experimental models were manufactured in-house using the injection-moulding
      procedure together with a commercially available photoelastic material. The
      material was mechanically characterised prior to testing, with models examined
      under three loading regimes (80, 120 and 160mmHg). Each experimental model was
      imaged using computed tomography (CT) and reconstructed in three dimensions (3D)
      for numerical analyses. Experimental wall strain was measured and numerical wall
      strain calculated with finite element analysis (FEA). Results were qualitatively
      and quantitatively compared. There was good qualitative agreement between the
      experimental and numerical methods, with similar trends apparent throughout all
      models at all pressures. Overall, acceptable percentage errors between the
      techniques were observed for all models. Median errors of -6.5%, -0.4% and 3.9%
      for the models at 80, 120 and 160mmHg pressures, respectively, were determined.
      The photoelastic method is a very useful experimental tool that provides instant,
      easy to interpret, information regarding wall strain. The technique is useful for
      validation of numerical AAA studies.

PMID- 22633539
TI  - Selected polymorphisms in sex hormone-related genes, circulating sex hormones and
      risk of endometrial cancer.
AB  - BACKGROUND: The role of estrogen and progesterone in the development of
      endometrial cancer is well documented. Few studies have examined the association
      of genetic variants in sex hormone-related genes with endometrial cancer risk.
      METHODS: We conducted a case-control study nested within three cohorts to examine
      the association of endometrial cancer risk with polymorphisms in hormone-related
      genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually
      matched controls. We also examined the association of these polymorphisms with
      circulating levels of sex hormones and SHBG in a cross-sectional analysis
      including 596 healthy postmenopausal women at blood donation (controls from this
      nested case-control study and from a nested case-control study of breast cancer
      in one of the three cohorts). RESULTS: Adjusting for endometrial cancer risk
      factors, the A allele of rs4775936 in CYP19 was significantly associated (OR(per
      allele)=1.22, 95% CI=1.01-1.47, p(trend)=0.04), while the T allele of rs10046 was
      marginally associated with increased risk of endometrial cancer (OR(per
      allele)=1.20, 95% CI=0.99-1.45, p(trend)=0.06). PGR rs1042838 was also marginally
      associated with risk (OR(per allele)=1.25, 95% CI=0.96-1.61, p(trend)=0.09). No
      significant association was found for the other polymorphisms, i.e. CYP1B1
      rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693.
      Rs8175347 was significantly associated with postmenopausal levels of estradiol,
      free estradiol and estrone and rs6259 with SHBG and estradiol. CONCLUSION: Our
      findings support an association between genetic variants in CYP19, and possibly
      PGR, and risk of endometrial cancer.

PMID- 22633541
TI  - Older age and capacity of colony forming unit in autologous peripheral derived
      hematopoietic cells.
AB  - BACKGROUND: Aging decreases bone marrow cellularity and alters the frequencies of
      stem cells. Aged hematopoietic stem cells can differ from their younger
      counterparts in functional capacity. STUDY DESIGN AND METHODS: We aimed to
      evaluate the relation between the age and the ability of colony forming capacity
      of peripheral blood-derived hematopoietic cell products collected for autologous
      stem cell transplantation (AHSCT). RESULTS: Elderly patients could be mobilized
      with lower total collected CD34+ cells. Colony forming capacity did not differ
      between young and old patients. CONCLUSION: This results can be translated into
      clinic as higher numbers of AHSCT candidates over age 60.

PMID- 22633542
TI  - The Canadian Association of Radiation Oncology scope of practice guidelines for
      lung, liver and spine stereotactic body radiotherapy.
AB  - AIMS: The Canadian Association of Radiation Oncology-Stereotactic Body
      Radiotherapy (CARO-SBRT) Task Force was established in 2010. The aim was to
      define the scope of practice guidelines for the profession to ensure safe
      practice specific for the most common sites of lung, liver and spine SBRT.
      MATERIALS AND METHODS: A group of Canadian SBRT experts were charged by our
      national radiation oncology organisation (CARO) to define the basic principles
      and technologies for SBRT practice, to propose the minimum technological
      requirements for safe practice with a focus on simulation and image guidance and
      to outline procedural considerations for radiation oncology departments to
      consider when establishing an SBRT programme. RESULTS: We recognised that SBRT
      should be considered as a specific programme within a radiation department, and
      we provide a definition of SBRT according to a Canadian consensus. We outlined
      the basic requirements for safe simulation as they pertain to spine, lung and
      liver tumours, and the fundamentals of image guidance. The roles of the radiation
      oncologist, medical physicist and dosimetrist have been detailed such that we
      strongly recommend the development of SBRT-specific teams. Quality assurance is a
      key programmatic aspect for safe SBRT practice, and we outline the basic
      principles of appropriate quality assurance specific to SBRT. CONCLUSION: This
      CARO scope of practice guideline for SBRT is specific to liver, lung and spine
      tumours. The task force recommendations are designed to assist departments in
      establishing safe and robust SBRT programmes.

PMID- 22633543
TI  - [Ocular involvement of chronic myeloid leukemia].

PMID- 22633544
TI  - Nano or micro? A mechanism on thermal decomposition of ammonium perchlorate
      catalyzed by cobalt oxalate.
AB  - Micrometer-sized cobalt oxalates with different morphologies have been prepared
      in the presence of surfactants. The effect of catalysts morphology on the thermal
      decomposition of ammonium perchlorate (AP) was evaluated by differential thermal
      analysis (DSC). Remarkably, contrary to the well-accepted concepts, no direct
      relationship between the morphologies of catalysts and their activities has been
      observed. Based on the structural and morphological variation of the catalysts
      during the reaction, a catalytic mechanism on thermal decomposition of ammonium
      perchlorate catalyzed by cobalt oxalate is proposed. We believe that it is the
      "self-crushing and self-distributed" occurred within the reaction that really
      works for the improvement of the overall catalytic activities. In this process,
      both catalysts and reactants have been crashed and distributed uniformly in an
      automatic way. This work provides an in-depth insight into the thermal
      decomposition mechanism of AP as catalyzed by oxalates.

PMID- 22633545
TI  - Utilization of recycled charcoal as a thermal source and adsorbent for the
      treatment of PCDD/Fs contaminated sediment.
AB  - A novel heat treatment process in which charcoal was used as both a thermal
      source and an adsorbent was investigated as a low-cost method for removal of
      polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs) from solids. Three laboratory scale experiments involving various ratios
      of charcoal to contaminated sediment and air superficial velocities were
      performed. The results indicated that the total and toxic equivalency quantities
      (TEQ) concentrations of PCDD/Fs decreased significantly in the treated sediment
      of all runs with removal efficiencies greater than 96% and 90%, which resulted in
      residual concentrations below the Japanese standard limit of 0.15ng-TEQg(-1). The
      charcoal/contaminated sediment ratio and air superficial velocity were
      determinant factors controlling the PCDD/Fs concentrations and homologue profiles
      in effluent. As the air superficial velocity increased and charcoal/contaminated
      sediment ratio decreased, more PCDD/Fs were released from the sediment as fly
      ash, making them less likely to remain in the treated sediment. These phenomena
      were likely a result of the vapor pressure of PCDD/Fs, contact time with effluent
      gas and amount of PCDD/Fs adsorbed by charcoal. The developed process would
      promise an alternative to a conventional remediation process for PCDD/Fs
      contaminated solids.

PMID- 22633546
TI  - [Urological cancers: ECCO/ESMO congress 2011].
AB  - In the Congress of European Cancer Organisation (ECCO)/European Society for
      Medical Oncology (ESMO), which took place in Stockholm between 23 and 27
      September 2011, urological cancers were the subject of various oral presentations
      and posters. A selection of the more innovative researches, likely to change the
      patients' management was performed. In prostate cancer, abiraterone acetate
      should be indicated in patients previously treated with docetaxel and sipuleucel
      T in patients with asymptomatic or minimally symptomatic castrate-resistant
      prostate cancer. Alpharadine should be indicated in patients with symptomatic
      bone metastases and denosumab in non-metastatic prostate cancer patients with a
      high risk of developing bone metastases. In metastatic renal clear cell
      carcinoma, the genetic polymorphisms are predictive for efficacy of anti
      angiogenic agents. Targeting both vascular endothelial growth factor (VEGF) and
      fibroblast growth factor (FGF) pathways is a very promising strategy. In
      urothelial cancer, two molecules are promising, the belinostat and the
      bortezomib. Other news on penile cancer and testicular seminoma are discussed.

PMID- 22633547
TI  - Cervical neck dissection for complete responders in head-and-neck: a utilitarian
      ideal? In regard to Thariat et al "Prediction of neck dissection requirement
      after definitive radiotherapy for head-and-neck squamous cell carcinoma." (Int J
      Radiat Oncol Biol Phys 2012;82:e367-e374).

PMID- 22633548
TI  - Re-irradiation strategies for head-and-neck cancers: implications for
      stereotactic body radiotherapy: in regard to Chen et al (Int J Radiant Oncol Biol
      Phys 2011;81:1211-1219).

PMID- 22633549
TI  - In regard to "Impact of [11C]methionine positron emission tomography for target
      definition of glioblastoma multiforme in radiation therapy planning." (Int J
      Radiat Oncol Biol Phys 2012;82:83-89).

PMID- 22633550
TI  - National Residency Matching Program (NRMP) results for radiation oncology: 2011
      update.

PMID- 22633551
TI  - Prognostic indexes for brain metastases: which is the most powerful?
AB  - PURPOSE: The purpose of the present study was to compare the prognostic indexes
      (PIs) of patients with brain metastases (BMs) treated with whole brain
      radiotherapy (WBRT) using an artificial neural network. This analysis is
      important, because it evaluates the prognostic power of each PI to guide clinical
      decision-making and outcomes research. METHODS AND MATERIALS: A retrospective
      prognostic study was conducted of 412 patients with BMs who underwent WBRT
      between April 1998 and March 2010. The eligibility criteria for patients included
      having undergone WBRT or WBRT plus neurosurgery. The data were analyzed using the
      artificial neural network. The input neural data consisted of all prognostic
      factors included in the 5 PIs (recursive partitioning analysis, graded prognostic
      assessment [GPA], basic score for BMs, Rotterdam score, and Germany score). The
      data set was randomly divided into 300 training and 112 testing examples for
      survival prediction. All 5 PIs were compared using our database of 412 patients
      with BMs. The sensibility of the 5 indexes to predict survival according to their
      input variables was determined statistically using receiver operating
      characteristic curves. The importance of each variable from each PI was
      subsequently evaluated. RESULTS: The overall 1-, 2-, and 3-year survival rate was
      22%, 10.2%, and 5.1%, respectively. All classes of PIs were significantly
      associated with survival (recursive partitioning analysis, P < .0001; GPA, P <
      .0001; basic score for BMs, P = .002; Rotterdam score, P = .001; and Germany
      score, P < .0001). Comparing the areas under the curves, the GPA was
      statistically most sensitive in predicting survival (GPA, 86%; recursive
      partitioning analysis, 81%; basic score for BMs, 79%; Rotterdam, 73%; and Germany
      score, 77%; P < .001). Among the variables included in each PI, the performance
      status and presence of extracranial metastases were the most important factors.
      CONCLUSION: A variety of prognostic models describe the survival of patients with
      BMs to a more or less satisfactory degree. Among the 5 PIs evaluated in the
      present study, GPA was the most powerful in predicting survival. Additional
      studies should include emerging biologic prognostic factors to improve the
      sensibility of these PIs.

PMID- 22633553
TI  - Implanted dosimeters identify radiation overdoses during IMRT for prostate
      cancer.
AB  - PURPOSE: Image-guided dose-escalated radiotherapy is the standard of care for the
      treatment of prostate cancer. Although many published methods are available that
      account for prostate motion during delivery, evidence demonstrating that the
      planned dose is actually delivered on a daily basis is lacking. We report our
      initial clinical experience using implantable dosimeters to quantify and adjust
      the dose received during intensity-modulated radiotherapy (IMRT). METHODS AND
      MATERIALS: A total of 20 patients undergoing IMRT with cone-beam computed
      tomography (CT) image guidance for prostate cancer had the dose verification
      system with radiopaque metal-oxide-semiconductor field effect transistor
      dosimeters implanted before treatment planning. All patients underwent planning
      with CT simulation in the supine position with custom immobilization, and the
      implanted dosimeters were located in the IMRT plans. The predicted dose for each
      dosimeter was defined and compared with the wireless readings before and after
      each treatment session. Investigations by physicians and medical physicists were
      initiated for two or more discrepancies >6% for any five consecutive fractions or
      for any discrepancy >=10%. RESULTS: Using implanted in vivo dosimeters, dose
      measurements consistently >6% greater than the predicted values were observed
      during treatment for 3 of 20 prostate cancer patients who received IMRT with
      daily image guidance. A review of the daily cone-beam CT images revealed
      acceptable alignment of the prostate target volumes and implanted dosimeters but
      identified significant anatomic changes within the treated region. Repeat CT
      simulation and RT planning was performed, with resolution of the dose
      discrepancies in all 3 cases with the adoption of a new IMRT plan. CONCLUSIONS:
      Our report illustrates the potential effect of implanted in vivo dosimetry for
      prostate IMRT and emphasizes the importance of careful planning and delivery with
      attention to systematic shifts or anatomic changes that could alter the dose
      distributions.

PMID- 22633552
TI  - Clinical outcome of patients treated with 3D conformal radiation therapy (3D-CRT)
      for prostate cancer on RTOG 9406.
AB  - PURPOSE: Report of clinical cancer control outcomes on Radiation Therapy Oncology
      Group (RTOG) 9406, a three-dimensional conformal radiation therapy (3D-CRT) dose
      escalation trial for localized adenocarcinoma of the prostate. METHODS AND
      MATERIALS: RTOG 9406 is a Phase I/II multi-institutional dose escalation study of
      3D-CRT for men with localized prostate cancer. Patients were registered on five
      sequential dose levels: 68.4 Gy, 73.8 Gy, 79.2 Gy, 74 Gy, and 78 Gy with 1.8
      Gy/day (levels I-III) or 2.0 Gy/day (levels IV and V). Neoadjuvant hormone
      therapy (NHT) from 2 to 6 months was allowed. Protocol-specific, American Society
      for Therapeutic Radiation Oncology (ASTRO), and Phoenix biochemical failure
      definitions are reported. RESULTS: Thirty-four institutions enrolled 1,084
      patients and 1,051 patients are analyzable. Median follow-up for levels I, II,
      III, IV, and V was 11.7, 10.4, 11.8, 10.4, and 9.2 years, respectively. Thirty
      six percent of patients received NHT. The 5-year overall survival was 90%, 87%,
      88%, 89%, and 88% for dose levels I-V, respectively. The 5-year clinical disease
      free survival (excluding protocol prostate-specific antigen definition) for
      levels I-V is 84%, 78%, 81%, 82%, and 82%, respectively. By ASTRO definition, the
      5-year disease-free survivals were 57%, 59%, 52%, 64% and 75% (low risk); 46%,
      52%, 54%, 56%, and 63% (intermediate risk); and 50%, 34%, 46%, 34%, and 61% (high
      risk) for levels I-V, respectively. By the Phoenix definition, the 5-year disease
      free survivals were 68%, 73%, 67%, 84%, and 80% (low risk); 70%, 62%, 70%, 74%,
      and 69% (intermediate risk); and 42%, 62%, 68%, 54%, and 67% (high risk) for
      levels I-V, respectively. CONCLUSION: Dose-escalated 3D-CRT yields favorable
      outcomes for localized prostate cancer. This multi-institutional experience
      allows comparison to other experiences with modern radiation therapy.

PMID- 22633554
TI  - Magnetic resonance imaging-based radiation-absorbed dose estimation of 166Ho
      microspheres in liver radioembolization.
AB  - PURPOSE: To investigate the potential of magnetic resonance imaging (MRI) for
      accurate assessment of the three-dimensional (166)Ho activity distribution to
      estimate radiation-absorbed dose distributions in (166)Ho-loaded poly (L-lactic
      acid) microsphere ((166)Ho-PLLA-MS) liver radioembolization. METHODS AND
      MATERIALS: MRI, computed tomography (CT), and single photon emission CT (SPECT)
      experiments were conducted on an anthropomorphic gel phantom with tumor
      simulating gel samples and on an excised human tumor-bearing liver, both
      containing known amounts of (166)Ho-PLLA-MS. Three-dimensional radiation-absorbed
      dose distributions were estimated at the voxel level by convolving the (166)Ho
      activity distribution, derived from quantitative MRI data, with a (166)Ho dose
      point-kernel generated by MCNP (Monte Carlo N-Particle transport code) and from
      Medical Internal Radiation Dose Pamphlet 17. MRI-based radiation-absorbed dose
      distributions were qualitatively compared with CT and autoradiography images and
      quantitatively compared with SPECT-based dose distributions. Both MRI- and SPECT
      based activity estimations were validated against dose calibrator measurements.
      RESULTS: Evaluation on an anthropomorphic phantom showed that MRI enables
      accurate assessment of local (166)Ho-PLLA-MS mass and activity distributions, as
      supported by a regression coefficient of 1.05 and a correlation coefficient of
      0.99, relating local MRI-based mass and activity calculations to reference values
      obtained with a dose calibrator. Estimated MRI-based radiation-absorbed dose
      distributions of (166)Ho-PLLA-MS in an ex vivo human liver visually showed high
      correspondence to SPECT-based radiation-absorbed dose distributions. Quantitative
      analysis revealed that the differences in local and total amounts of (166)Ho-PLLA
      MS estimated by MRI, SPECT, and the dose calibrator were within 10%. Excellent
      agreement was observed between MRI- and SPECT-based dose-volume histograms.
      CONCLUSIONS: Quantitative MRI was demonstrated to provide accurate three
      dimensional (166)Ho-PLLA-MS activity distributions, enabling localized
      intrahepatic radiation-absorbed dose estimation by convolution with a (166)Ho
      dose point-kernel for liver radioembolization treatment optimization and
      evaluation.

PMID- 22633555
TI  - A refinement of the Kirchhoff approximation to the scattered elastic fields.
AB  - We study two canonical problems, diffraction of a plane elastic wave by a thin
      crack and diffraction of a plane elastic wave by a wedge, both in the high
      frequency regime. In applications this regime is usually treated using the so
      called Kirchhoff approximation. It is very easy to implement but there are
      situations when it is known to give distorted results. We discuss an easy
      correction procedure, which is applicable not only in geometrical regions but
      inside penumbras too. The procedure involves a version of the Physical Theory of
      Diffraction that relies on the Geometrical Theory of Diffraction rather than the
      full solution of the corresponding canonical problem.

PMID- 22633557
TI  - Is maximum stimulation intensity required in the assessment of muscle activation
      capacity?
AB  - Voluntary activation assessment using the interpolation twitch technique (ITT)
      has almost invariably been done using maximal stimulation intensity, i.e., an
      intensity beyond which no additional joint moment or external force is produced
      by increasing further the intensity of stimulation. The aim of the study was to
      identify the minimum stimulation intensity at which percutaneous ITT yields valid
      results. Maximal stimulation intensity and the force produced at that intensity
      were identified for the quadriceps muscle using percutaneous electrodes in eight
      active men. The stimulation intensities producing 10-90% (in 10% increments) of
      that force were determined and subsequently applied during isometric contractions
      at 90% of maximum voluntary contraction (MVC) via twitch doublets. Muscle
      activation was calculated with the ITT and pain scores were obtained for each
      stimulation intensity and compared to the respective values at maximum
      stimulation intensity. Muscle activation at maximal stimulation intensity was
      91.6 (2.5)%. The lowest stimulation intensity yielding comparable muscle
      activation results to maximal stimulation was 50% (88.8 (3.9)%, p < 0.05). Pain
      score at maximal stimulation intensity was 6.6 (1.5) cm and it was significantly
      reduced at 60% stimulation intensity (3.7 (1.5) cm, p < 0.05) compared to maximal
      stimulation intensity. Submaximal stimulation can produce valid ITT results while
      reducing the discomfort obtained by the subjects, widening the assessment of ITT
      to situations where discomfort may otherwise impede maximal electrostimulation.

PMID- 22633556
TI  - Impact of pharmacist-managed erythropoiesis-stimulating agents clinics for
      patients with non-dialysis-dependent CKD.
AB  - BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are associated with serious
      adverse events, and maintaining hemoglobin levels within a narrow range can be
      difficult. We examined the quality of ESA prescribing and monitoring in
      pharmacist-managed ESA clinics versus usual care in patients with non-dialysis
      dependent chronic kidney disease (NDD-CKD). STUDY DESIGN: Historical cohort.
      SETTING & PARTICIPANTS: Outpatients receiving ESAs for NDD-CKD at 10 Veterans
      Affairs Medical Centers with both pharmacist-managed ESA clinics (n = 314) and
      physician-based care (ie, usual care; n = 91) and 6 sites with usual care only (n
      = 167) on January 1, 2009, were followed up for 6 months. PREDICTOR: Type/site of
      care (ie, pharmacist-managed ESA clinic, usual care at ESA clinic site, usual
      care site). OUTCOMES: Primary outcomes were proportion of hemoglobin values in
      the target range of 10-12 g/dL, ESA dose, and frequency of hemoglobin monitoring.
      Factors associated with hemoglobin values out of target range were identified
      using multinomial logistic regression. RESULTS: More hemoglobin values were in
      the target range in pharmacist-managed ESA clinics (71.1% vs 56.9% for usual-care
      sites; P < 0.001). The average 30-day dose of darbepoetin was 163 MUg in
      pharmacist-managed ESA clinic patients versus 240 MUg in usual-care site patients
      and 258 MUg in usual-care patients at ESA clinic sites. For epoetin,
      corresponding average 30-day doses were 44,890 versus 47,141 and 57,436 IU.
      Veterans in pharmacist-managed ESA clinics had more hemoglobin measurements on
      average (5.8 vs 3.6 in usual-care sites and 3.8 in usual care at ESA clinic
      sites; P = 0.007). In the multinomial model, usual care was associated with
      hemoglobin levels out of target range, whereas heart failure and diabetes were
      associated with values in range. LIMITATIONS: We could not assess whether
      different hemoglobin targets were used by usual-care providers. CONCLUSIONS:
      Relative to usual care, pharmacist-managed clinics provided improved quality of
      ESA dosing and monitoring for patients with NDD-CKD.

PMID- 22633558
TI  - Reliability of knee joint muscle activity during weight bearing force control.
AB  - We developed a novel approach that requires subjects to produce and finely tune
      ground reaction forces (GRFs) while standing. The aim of this study was to
      examine the reliability of electromyographic data recorded during these tasks.
      Healthy young adults stood with their dominant leg in a boot fixed to a force
      platform. A target matching protocol required subjects to control both the
      direction and magnitude of GRF along the horizontal plane while maintaining
      constant inferior-superior loads of 50% body-weight (BW). Each target matching
      task was repeated three times in a random order. Subjects were retested with the
      same protocol 2-3 days later. Normalised electromyography data of eight muscles
      crossing the knee joint was collected for each successful target match. A random
      model, single measures intra-class correlation analysed the reliability for both
      test-retest and intra-day results, in addition to inter-subject reliability. The
      GRFs required to meet the targets were comparable to a range of activities of
      daily living, ranging from 0.48 to 0.58 N/kg of BW in the horizontal plane while
      maintaining 50% BW in the vertical plane. We observed moderate to high ICC values
      (0.60-0.993) for most muscles in most directions, indicating low within-subject
      variance. In addition, moderate to high between-subject reliability was observed
      in all eight muscle activation profiles, indicating subjects used similar
      neuromuscular control strategies to achieve the desired GRFs. In conclusion, our
      protocol identifies non-random weight-bearing motor control strategies while
      generating direction dependent GRFs. These results provide reliable insight into
      knee joint stabilisation strategies during weight bearing.

PMID- 22633560
TI  - Coffee, caffeine and health: what's in your cup?

PMID- 22633561
TI  - Carpe diem, Carpe ampulla: a numerical model as an aid to the design of child
      resistant closures.
AB  - The population of most developed countries is ageing. Despite continuing medical
      advances, ageing brings with it a host of issues, not least a loss in strength
      and dexterity. One major area of concern is the ability of elderly consumers to
      access packaged goods such as food and medicines. In previous studies, the
      authors developed a numerical model of a human hand that was used to investigate
      the effect of physical dimensions and choice of grip on joint stresses to aid the
      understanding between physical effort, ability and discomfort. This previous work
      was supported by ethnographic studies and led to recommendations for packaging
      design. In this paper, a small ethnographic study is undertaken which identifies
      the grip types used to access to a product that is known to cause particular
      difficulties for the elderly, the "squeeze and turn" child-resistant closure or
      CRC, commonly used on medicines and cleaning products. One of the grip types used
      was chosen to be modelled using the numerical model developed in previous studies
      by the author. Model geometry and loading were adapted to simulate the "squeeze
      and turn" nature of the initial opening for closures of this type. A series of
      studies were then undertaken using different hand geometries; an average male
      hand, an average female hand and a fifth percentile female hand. The prediction
      from the model here is that female users with smaller hands will experience more
      discomfort when accessing squeeze and turn CRC's and that the turn process whilst
      maintaining the squeeze is problematic.

PMID- 22633559
TI  - The use of evolutionary patterns in protein annotation.
AB  - With genomic data skyrocketing, their biological interpretation remains a serious
      challenge. Diverse computational methods address this problem by pointing to the
      existence of recurrent patterns among sequence, structure, and function. These
      patterns emerge naturally from evolutionary variation, natural selection, and
      divergence--the defining features of biological systems--and they identify
      molecular events and shapes that underlie specificity of function and allosteric
      communication. Here we review these methods, and the patterns they identify in
      case studies and in proteome-wide applications, to infer and rationally redesign
      function.

PMID- 22633562
TI  - Spontaneous bilateral carotid artery dissection following cervical manipulation.
AB  - We report an autopsy case of a bilateral carotid artery dissection, following
      cervical manipulation by a chiropractor. To establish the etiology of a cervical
      artery dissection is important in view of possible legal implications and to
      exclude hereditary disorders, since cervical artery dissection has been linked to
      several arteriopathies. The underlying arteriopathy in the presented case was an
      idiopathic cystic medial degeneration. This report emphasizes the role of the
      pathologist in defining the underlying arteriopathy in carotid artery dissection.

PMID- 22633563
TI  - An autopsy case of a decomposed body with keyhole gunshot wound and secondary
      skull fractures.
AB  - The decomposed body of a 53 or 57-year-old male was found with a gun in a locked
      car parked in a coin-operated parking lot. During autopsy, the entrance wound in
      the frontal bone showed a characteristic keyhole defect with internal and
      external beveling. There was no exit wound. The fragmented bullet traveled
      downward within the calvarium and struck the right orbital plate. Two independent
      linear fractures were observed away from the entrance. These were believed to be
      secondary fractures resulting neither from internal ricochet of the bullet nor
      from direct blunt force to the head. Although decomposition complicated the
      evaluation of the gunshot wound characteristics, microscopic examination
      confirmed large quantities of soot along the wound tract, supporting our
      conclusion that the range of fire was contact.

PMID- 22633564
TI  - OprD mutations and inactivation, expression of efflux pumps and AmpC, and metallo
      beta-lactamases in carbapenem-resistant Pseudomonas aeruginosa isolates from
      South Korea.
AB  - Among 213 Pseudomonas aeruginosa isolates collected from 10 South Korean
      hospitals, 57 isolates (26.8%) were carbapenem-resistant. All but three of the
      isolates had a relevant decrease of oprD expression. However, decreased oprD
      expression was also detected in five of ten carbapenem-susceptible isolates.
      Outer membrane protein analysis confirmed porin loss in carbapenem-resistant P.
      aeruginosa isolates. Based on the mutations of oprD gene sequences, carbapenem
      resistant P. aeruginosa isolates could be classified into five oprD mutational
      groups. However, there was no difference of OprD expression or carbapenem minimum
      inhibitory concentrations among the five mutational groups. Among the 57
      carbapenem-resistant P. aeruginosa isolates, 41 (71.9%) overexpressed efflux
      systems or ampC. MexAB-OprM and AmpC overexpression (56.1% and 47.4%,
      respectively) was prevalent and was significantly associated with carbapenem
      resistance. However, no synergistic effect of efflux systems and AmpC on
      carbapenem resistance was evident. In conclusion, combination of several mutation
      driven mechanisms leading to OprD inactivation and overexpression of efflux
      systems was the main carbapenem resistance mechanism, but acquisition of a
      transferable resistance determinant such as metallo-beta-lactamase could be
      problematic in clinical settings in South Korea.

PMID- 22633565
TI  - High vancomycin minimum inhibitory concentration is a predictor of mortality in
      meticillin-resistant Staphylococcus aureus bacteraemia.
AB  - Failure of vancomycin in the treatment of meticillin-resistant Staphylococcus
      aureus (MRSA) bacteraemia has been reported despite full susceptibility of the
      organism to vancomycin. A retrospective observational cohort study including 137
      patients with MRSA bacteraemia was performed at two centres in South Korea during
      2009-2010. A total of 137 patients with MRSA bacteraemia receiving vancomycin
      therapy were enrolled during the study period. Isolates from 13 (9.5%) of the 137
      patients had minimum inhibitory concentrations (MICs) >=1 MUg/mL. The 30-day
      cumulative survival was 53.8% for patients infected with isolates having a MIC>=1
      MUg/mL and 79.8% for patients infected with isolates having a MIC<1 MUg/mL (log
      rank test, P=0.026). Vancomycin MIC>=1 MUg/mL [hazard ratio (HR)=7.0, 95%
      confidence interval (CI) 2.2-22.1; P=0.001], nosocomial acquisition of
      bacteraemia (HR=5.4, 95% CI 1.4-20.1; P=0.013), rapidly fatal underlying diseases
      (HR=20.5, 95% CI 3.9-106.4; P<0.001), presentation with septic shock (HR=8.4, 95%
      CI 3.0-23.3; P<0.001), presence of complicated infections (HR=5.6, 95% CI 2.0
      15.8; P=0.001) and persistent MRSA bacteraemia for >=3 days (HR=4.2, 95% CI 1.4
      12.7; P=0.012) were independent predictors of 30-day mortality in patients with
      MRSA bacteraemia. In patients with high Pitt bacteraemia scores (Pitt score >=2),
      the delay in initiation of vancomycin therapy was significantly different between
      non-survivors and survivors (2.4 days vs. 1.1 days; P=0.012). Vancomycin MIC>=1
      MUg/mL had a significant impact on mortality of patients with MRSA bacteraemia.
      These findings support early consideration of alternative anti-MRSA agents in
      patients with MRSA bacteraemia who have high vancomycin MICs as well as prompt
      initiation of anti-MRSA treatment in patients with MRSA bacteraemia, especially
      those with high Pitt scores.

PMID- 22633566
TI  - Lemierre's syndrome due to Fusobacterium necrophorum.
AB  - We present a case of a patient with Lemierre's syndrome caused by Fusobacterium
      necrophorum who developed a right frontal lobe brain abscess. We summarise the
      epidemiology, microbiology, pathogenesis, clinical presentation, diagnosis,
      complications, therapy, and outcomes of Lemierre's syndrome. F necrophorum is
      most commonly associated with Lemierre's syndrome: a septic thrombophlebitis of
      the internal jugular vein. Patients usually present with an exudative
      tonsillitis, sore throat, dysphagia, and unilateral neck pain. Diagnosis of
      septic thrombophlebitis is best confirmed by obtaining a CT scan of the neck with
      contrast. Complications of the disease include bacteraemia with septic abscesses
      to the lungs, joints, liver, peritoneum, kidneys, and brain. Treatment should
      include a prolonged course of intravenous beta-lactam antibiotic plus
      metronidazole.

PMID- 22633567
TI  - Future directions in vitamin D and cardiovascular research.
AB  - AIMS: Evidence is accumulating that vitamin D status may influence the risk of
      cardiovascular disease (CVD). Final confirmation for a causal relationship
      between vitamin D and CVD is however still lacking. The present viewpoint article
      outlines several future research directions to close this gap. DATA SYNTHESIS:
      Future directions include the need of performing large randomised controlled
      supplementation trials with vitamin D in specific risk groups. In addition, large
      register sets of data on vitamin D supplementation can be used, provided that
      adequate statistical methods such as propensity score modelled analysis are
      applied. To better understand vitamin D-mediated effects on CVD risk, the routine
      measurement of circulating levels of the hormonal vitamin D form, 1,25
      dihydroxyvitamin D, is also necessary, in addition to the determination of its
      precursor 25-hydroxyvitamin D. Further, genetic association studies may help in
      clarifying the contribution of vitamin D to the development of CVD. Finally, the
      interrelationship of vitamin D with physical activity should be considered when
      studying CVD risk. CONCLUSIONS: Overall, it can be expected that the next 10-15
      years will provide an increased clarity concerning the role of vitamin D in CVD.

PMID- 22633568
TI  - Single site laparoscopic sleeve gastrectomy.

PMID- 22633569
TI  - Adult intussusception: diagnostic pitfalls, morbidity and mortality in a
      developing country.
AB  - OBJECTIVE: To study diagnostic pitfalls, morbidity and mortality of adult
      intussusception. PATIENTS AND METHODS: Retrospective study of adult patients
      records operated between 1979 and 2007 with the diagnosis of adult
      intussusception. RESULTS: We found 41 cases of adult intussusception. The mean
      age was 35.2 years (standard deviation (SD)=7.1). The delay between onset and
      medical consultation was 15 days. The diagnosis was made pre-operatively in 11
      cases. Abdominal ultrasound showed an abdominal mass in 11 cases. Ileo-ileal
      intussusception was most frequent (16 cases). Intussusception was secondary in 24
      cases. There were seven instances of intestinal necrosis. Intestinal resection
      was performed in 34 cases. Surgical site infection occurred in four patients,
      three patients died. CONCLUSION: The pre-operative diagnosis of acute intestinal
      intussusception is difficult. Morbidity and mortality rates are high. Improved
      diagnostic investigations in developing countries could improve the prognosis of
      this condition.

PMID- 22633570
TI  - Is advanced age still a contra-indication to surgery for esophageal cancer?

PMID- 22633571
TI  - Abdominal tuberculosis.

PMID- 22633572
TI  - Complete calcification of colorectal liver metastases on imaging after
      chemotherapy does not indicate sterilization of disease.
AB  - BACKGROUND: The significance of complete calcification of liver metastases on
      imaging is unknown. This study was conducted to determine whether complete
      calcification of liver metastases after chemotherapy, as assessed by imaging, was
      synonymous with sterilization of disease. METHODS: Imaging by triphasic contrast
      enhanced helical CT scan and abdominal ultrasound showed complete calcification
      of eight liver metastases in four patients after systemic chemotherapy. All eight
      completely calcified liver metastases were resected within four weeks of imaging.
      Histological and surgical findings were analyzed to see whether there was any
      correlation between radiological and pathological status for completely calcified
      liver metastases. RESULTS: The pretreatment median diameter at initial imaging of
      the eight liver metastases that became completely calcified after chemotherapy
      was 24 mm. In all eight resected calcified liver metastases, pathological
      examination showed the presence of residual viable tumor cells. Most of the tumor
      volume was occupied by calcification, necrosis and fibrosis; but small discrete
      islands of viable tumor cells were detected at the periphery of lesions.
      CONCLUSIONS: This preliminary study shows that although imaging evidence of
      complete calcification of liver metastases may be a good indicator of
      chemotherapy response, it does not imply sterilization of the malignancy.

PMID- 22633573
TI  - Enhancement of photocatalytic activity of nano-scale TiO2 particles co-doped by
      rare earth elements and heteropolyacids.
AB  - Nano-scale TiO(2) photocatalysts co-doped by rare earth ions (La(3+), Ce(3+)) and
      heteropolyacids were designed and prepared by sol-gel method to probe synergistic
      effect on photocatalytic elimination of organic compounds, and their
      physicochemical properties were characterized by X-ray diffraction (XRD),
      specific surface area and porosity (BET and BJH), high resolution transmission
      electron microscopy (HRTEM), UV-vis diffuse reflectance spectroscopy (UV-vis
      DRS), and X-ray photoelectron spectroscopy (XPS) as well as Raman spectroscopy.
      The photocatalytic activity of prepared catalysts was evaluated by the
      degradation of methylene blue (MB) in water under UV-light irradiation. The
      results showed that the co-doping of the rare earth ions and heteropolyacids can
      significantly improve the photocatalytic activity of prepared composite
      photocatalysts due to the efficient inhibition of the recombination of
      photogenerated electron-hole pairs. The enhancement mechanism of co-doping of the
      rare earth ions and heteropolyacids on TiO(2) is also discussed.

PMID- 22633574
TI  - Synthesis, characterization, and catalytic performance of copper-containing SBA
      15 in the phenol hydroxylation.
AB  - A series of copper-containing SBA-15 samples were successfully synthesized via
      evaporation-induced self-assembly route. The resulting materials were
      characterized by X-ray diffraction (XRD), (29)Si MAS NMR spectroscopy,
      transmission electron microscopy (TEM), N(2) sorption, inductively coupling
      plasma-atomic emission spectrometer (ICP-AES), thermogravimetry, and differential
      thermal analysis (TG-DTA), Fourier-transform infrared spectroscopy (FT-IR), UV
      vis diffuse reflectance spectra (UV-vis) and X-ray photoelectron spectroscopy
      (XPS). The results indicated that: (1) all the samples exhibited typical
      hexagonal arrangement of mesoporous structure; (2) copper ions could be
      incorporated into the framework of SBA-15; (3) the addition of urea in the
      hydrothermal stage efficiently reduced the leaching of copper and improved the
      thermal stability of the mesoporous materials. Catalytic performances of the
      obtained materials were evaluated in the hydroxylation of phenol with H(2)O(2).
      The catalytic tests showed that the synthesized materials exhibited high activity
      for this reaction and copper ions in the framework were more active than copper
      species in the extra-framework position. The nitric acid treatment on the samples
      removed the bulk CuO species, which resulted in a dramatic increase in the
      catalytic activity.

PMID- 22633575
TI  - Application of hydrophobic silica based aerogels and xerogels for removal of
      toxic organic compounds from aqueous solutions.
AB  - This work is devoted to the application of hydrophobic silica based aerogels and
      xerogels for the removal of three toxic organic compounds from aqueous solutions.
      These materials were tested and characterized regarding their morphology,
      particle size distribution, surface area and porous structure. The equilibrium
      tests were carried out at different adsorbate concentrations and the experimental
      data were correlated by means of Langmuir and Freundlich isotherms. The
      equilibrium data were well described by Langmuir and Freundlich in most cases.
      The maximum adsorption capacity by Langmuir model was observed for the adsorption
      of benzene onto aerogel (192.31 mg/g), though the most promising results were
      obtained for toluene adsorption due to the greater adsorption energy involved.
      Comparing these results with other reported results, the hydrophobic silica based
      aerogels/xerogels were found to exhibit a remarkable performance for the removal
      of benzene and toluene. In addition, the regeneration of previously saturated
      aerogel/toluene was also investigated by using an ozonation process. The
      adsorption/regeneration tests with ozone oxidation showed that the aerogel might
      be regenerated, nevertheless the materials lost their hydrophobicity and thus
      different methods should be evaluated in forthcoming investigations.

PMID- 22633576
TI  - Dual-responsive poly(styrene-alt-maleic acid)-graft-poly(N-isopropyl acrylamide)
      micelles as switchable emulsifiers.
AB  - Self-assembled polymeric micelles can be used as efficient particulate
      emulsifiers. To explore the relationship between micellar structure and
      emulsification performance, pH- and temperature-responsive self-assembled
      micelles were prepared and used as emulsifiers, based on a novel grafted polymer
      poly(styrene-alt-maleic acid)-graft-poly(N-isopropyl acrylamide) (PSMA-g-PNIPAm).
      Structure of PSMA-g-PNIPAm micelles varies in response to pH and temperature
      changes and can be classified into four typical states, including shrunken,
      moderately swollen, extremely swollen, and inverted states, confirmed by a
      combination of electrophoresis, dynamic light scattering (DLS), transmission
      electron microscopy (TEM), and (1)H NMR. This structural variation plays a key
      role in the emulsification performance of PSMA-g-PNIPAm micelles, according to
      the emulsifying characteristics of the four typical PSMA-g-PNIPAm micelles as
      well as the micellar morphologies on the surface of oil droplets as observed by
      SEM. Emulsions stabilised by micelles with moderately swollen structure are
      especially stable compared with either the shrunken micelles or the extremely
      swollen micelles, because the moderately swollen micelles combine the advantages
      of solid particulate emulsifiers and polymeric surfactants.

PMID- 22633577
TI  - Degradation of perchlorate in water using aqueous multivalent titanium: effect of
      titanium type, ionic strength, and metal and solid catalysts.
AB  - In this study, chemical degradation of perchlorate was investigated using
      partially oxidized titanium ions (Ti(II) and Ti(III)). Results of UV spectra
      showed that the patterns of absorbance at all ratios of F/Ti(0) were similar each
      other, except the lowest F/Ti(0) of 0.5 (25 mM F(-)) where mixture of Ti(II) and
      Ti(III) might be present, resulted in shift of the peak to wavelength of 480 nm.
      The rate of perchlorate degradation was fastest at lowest F/Ti(0) ratio. Among
      catalysts investigated, only rhenium enhanced the perchlorate degradation in the
      presence of Ti(II), but no effect of catalysts in Ti(III). In addition, high
      ionic strength did not enhance the perchlorate-Ti(III) reaction, but high acid
      concentration did. Addition of solid acid catalysts (SACs) to Ti(III) solution
      showed slower perchlorate degradation, probably due to decrease in Ti(III)
      concentration by adsorption onto SAC. Rate constants for perchlorate degradation
      in Ti(III) were twofold higher than in Ti(II) when 5 N HCl used.

PMID- 22633578
TI  - Has anybody seen my old friend Peplau? The absence of interpersonal curricula in
      programs of nursing.

PMID- 22633579
TI  - Anger in the trajectory of healing from childhood maltreatment.
AB  - When a girl is abused during childhood, she may not experience anger, only
      helplessness or numbness. Only later may the emotion of anger surface. Little is
      known about anger cognitions or behaviors as they occur across the years of the
      healing trajectory from childhood maltreatment. Data for the present secondary
      analysis were derived from a large narrative study of women thriving in adulthood
      despite childhood abuse. The purpose of this analysis was to examine the
      phenomenon of anger and its role in the recovery process of 6 midlife women. The
      6 cases were purposefully selected because their interviews contained rich
      descriptions of anger experiences. Because each woman was interviewed 3 times
      over a 6- to 12-month period, 18 transcripts were available for in-depth
      examination. A typology was constructed, depicting 5 types of anger. Anger ranged
      from nonproductive, self-castigating behavior to empowering, righteous anger that
      enabled women to protect themselves from further abuse and to advocate for abused
      children. Study findings are relevant to extant theories of women's anger and
      feminist therapies.

PMID- 22633580
TI  - Health service use among persons with self-reported depression: a longitudinal
      analysis of 7,164 women.
AB  - OBJECTIVE: Depression is a common mental disorder and a leading contributor to
      the global burden of disease. In Australia, depression is reportedly the leading
      cause of morbidity for young women. In addition to conventional treatments, there
      is also some evidence that there is common use of complementary and alternative
      medicine (CAM) among people with depressive symptoms. However, there has been
      little research focus upon broad health care and practitioner use (including
      consumption of both conventional and CAM practitioners as well as self-prescribed
      care) among young adults with depression. This article aims specifically to
      address this knowledge gap by providing the first longitudinal analysis of the
      use of health service among women with self-reported depression. METHODS: Data
      from a longitudinal cohort study (Australian Longitudinal Study on Women's
      Health) conducted over a 3-year period on 7,164 young Australian women were
      analyzed. Information on health status, health service use, and self-prescribed
      treatments was obtained from two questionnaires mailed to study participants in
      2003 and 2006. RESULTS: The study identified that only a small proportion of the
      women had sought professional assistance for their self-reported depression. It
      also shows that many women who reported depression used CAM alongside or as a
      complement to conventional health care services. In particular, young women who
      did not seek help for their depression were more likely to self-prescribe CAM
      than were women without depression. CONCLUSION: The frequent use of a range of
      conventional providers and practitioner-based CAM and self-prescribed CAM among
      women with self-reported depression warrants further investigation.

PMID- 22633581
TI  - Provision of preventive services for cancer and infectious diseases among
      individuals with serious mental illness.
AB  - Individuals living with serious mental illness (SMI) have increased mortality
      chiefly because of a higher prevalence of chronic disorders, including some
      cancers and infectious diseases. Although increased prevalence of these disorders
      may be attributable to lifestyle and risk behaviors, there is evidence that they
      may not be appropriately addressed by health professionals. We conducted a review
      of the literature describing preventive services for cancer and infectious
      diseases provided to individuals with SMI. Most studies demonstrated a 20%-30%
      reduced likelihood of breast, cervical, and colorectal cancer screening, or
      immunizations for influenza and pneumonia, in patients with SMI compared with
      those without SMI. This is most common in those with the most severe forms of
      SMI. HIV and hepatitis were more commonly screened for in people with SMI than
      the general population, likely because of the increased risk for these disorders
      within this group, but there were still substantial proportions of individuals
      with SMI who had never received a screening, or had not received a recent
      screening, for these disorders. The mental health nursing profession has an
      opportunity to address the disparity in care for cancer and infectious diseases,
      as well as other physical disorders, experienced by mental health consumers. With
      systemic support and ongoing education, mental health nurses may be capable of
      conducting or recommending screening for disorders and providing lifestyle
      advice. These practices may help to reduce the increased prevalence of chronic
      disease in SMI populations.

PMID- 22633582
TI  - Influence of race on outpatient commitment and assertive community treatment for
      persons with severe and persistent mental illness.
AB  - Critics of outpatient commitment (OPC) suggest that African Americans with severe
      and persistent mental illness may be more frequently subjected to coercive
      treatment. This study examines the frequency of use of OPC and assertive
      community treatment and compares their influence on the perceptions of procedural
      justice/choice and coercion/negative pressure on African Americans and Whites. No
      significant differences were found in the rate at which OPC was applied to
      African Americans or in the use of assertive community treatment. Although
      procedural justice/choice does contribute significantly to the perception of
      coercion/negative pressure in both groups, its influence is diminished in African
      Americans.

PMID- 22633583
TI  - Mental health of elders in retirement communities: is loneliness a key factor?
AB  - Loneliness is often manifested by intense feelings of emptiness and abandonment
      and can lead to depression and suicide. The prevalence of loneliness in older
      adults is estimated to be 40%. This secondary analysis examined differences
      between elders reporting and elders not reporting loneliness and the effect of
      gender on resourcefulness and measures of physical and mental health within the
      context of L. C. Hawkley and J. T. Cacioppo's (2010) theoretical model of
      loneliness. A descriptive, comparative design was used to examine gender
      differences and associations among loneliness and indicators of physical and
      mental health. Results indicated that for overall health, and indicators of
      physical health (functional status and number chronic conditions), no significant
      differences were found between those who reported loneliness and those who
      reported no loneliness. There were significant differences, however, between
      lonely elders and nonlonely elders on indicators of mental health, including both
      anxiety and depressive symptoms. Differences between lonely elders and nonlonely
      elders on measures of resourcefulness approached significance. The findings from
      this study suggest that intervention programs designed to prevent or reduce
      loneliness in older adults may be beneficial for preserving their mental health.

PMID- 22633584
TI  - What is good mental health nursing? A survey of Irish nurses.
AB  - The practice, theory, and preparation associated with nursing people with mental
      health issues has changed in profound ways in recent decades. This has in part
      been reflected by a shift in nurses identifying as being mental health rather
      than psychiatric nurses. Context, theory, and values shape what it means to be a
      mental health nurse. Thirty experienced mental health nurses in Ireland completed
      a survey on what good mental health nursing is and a definition induced from
      their responses. Mental health nursing is a professional, client-centered, goal
      directed activity based on sound evidence, focused on the growth, development,
      and recovery of people with complex mental health needs. It involves caring,
      empathic, insightful, and respectful nurses using interpersonal skills to draw
      upon and develop the personal resources of individuals and to facilitate change
      in partnership with the individual and in collaboration with friends, family, and
      the health care team. This appears to encapsulate the best of what it meant to be
      a psychiatric nurse, but challenges remain regarding how to reconcile or whether
      to discard coercive practices incompatible with mental health nursing.

PMID- 22633586
TI  - Development of an instrument to measure self-efficacy for social participation of
      people with mental illness.
AB  - Promoting social participation is consistent with the principles of psychiatric
      rehabilitation of people with severe mental illness, but lack of self-efficacy in
      social participation is a major barrier to the community integration of these
      people. The purpose of this study was to develop an instrument in the form of a
      mental illness scale (self-efficacy for social participation [SESP]) to measure
      self-efficacy in social participation among Japanese people and to evaluate the
      scale's reliability and validity. Devised from a content analysis of interviews
      with 12 patients regarding their participation in socialization programs, the
      scale consisted of 37 items. The scale's validity and reliability were tested in
      a total of 340 community-dwelling individuals with severe mental illness. The
      final scale consisted of four dimensions with 27 items. Internal consistency of
      the overall SESP-27 was excellent (alpha = .96). The scale demonstrated adequate
      criterion and construct validity and was psychometrically sound. The scale may
      offer clinicians a tool for planning how to help individuals with mental illness
      boost their self-efficacy in social participation and community integration.

PMID- 22633585
TI  - HIV disclosure by perinatal women in Thailand.
AB  - Little is known about HIV disclosure among perinatal women, although we do know
      that disclosure can facilitate timely initiation of appropriate interventions for
      infected individuals and their families. This study, therefore, examined
      predictors of HIV disclosure among perinatal Thai women. Data (N = 207) were
      extracted from two larger studies of depressive symptoms in HIV-positive pregnant
      or postpartum women in Thailand in which participants completed questionnaires.
      Most participants had low socioeconomic status. Logistic regression indicated
      that significant predictors of disclosure included older age, employment, and
      high family support. Psychiatric mental health nursing interventions to promote
      family support are critical during this time.

PMID- 22633587
TI  - Balancing risk in pursuit of the familiar: a research phenomenon.

PMID- 22633588
TI  - Like parent, like child: parent and child emotion dysregulation.
AB  - PURPOSE: This study examined the association between children's emotion
      regulatory processes and parents' emotional problems. DESIGN: A 5-year
      longitudinal study of families from Northwestern United States with data
      collected over 3 time points. Families were recruited in an effort to oversample
      for multiracial and African American families because these families have
      historically not been well represented in research studies. METHOD: Parental
      hostility characteristics and subclinical levels of depression were assessed in
      combination with teachers' reports of children's externalizing and internalizing
      behaviors. Ninety-one families with married parents and an elementary school-aged
      child participated in the study. FINDINGS: There was a significant main effect
      for the association between fathers' self-reports of hostility and teacher
      reports of children's externalizing behaviors. Neither parental hostility nor
      depressive symptoms were significantly associated with the children's
      internalizing behaviors. CONCLUSION: The results suggest that children's
      externalizing behaviors are associated with their fathers' dysregulated
      expression of hostility. CLINICAL RELEVANCE: Parent-child interactions are a key
      component of children's emotion regulation development. Our findings may guide
      health care professionals in identifying and intervening in parental behaviors,
      particularly fathers' behaviors, that may adversely affect the healthy emotional
      development of their children.

PMID- 22633589
TI  - Modified root submergence technique for multiple implant-supported maxillary
      anterior restorations in a patient with thin gingival biotype: a clinical report.

PMID- 22633590
TI  - Attachment of clips in a bar-retained maxillary implant overdenture: a clinical
      report.
AB  - Implant-supported overdentures are a good alternative for patients with
      conventional dentures that lack retention and stability. The most common
      prosthetic complications in mandibular and maxillary implant-supported
      overdentures are fracture and loosening of the attachment system. This clinical
      report describes the treatment of a completely edentulous patient with sinus
      floor elevation by using bone from the iliac crest and the insertion of 4
      implants in the maxilla and mandible followed by implant-supported overdentures.
      The technical procedure for the attachment of clips to an acrylic resin
      overdenture base with the use of metal reinforcement is described. The advantage
      of this attachment procedure is an improved attachment system with less fracture
      and less loosening of the clips.

PMID- 22633591
TI  - The effect of number and distribution of unsplinted maxillary implants on the
      load transfer in implant-retained maxillary overdentures: an in vitro study.
AB  - STATEMENT OF PROBLEM: There is little information as to how the number and
      distribution of implants affect the amount of load transmitted to the palate in
      implant-retained maxillary overdentures. PURPOSE: The purpose of this study was
      to evaluate the effect of the number and distribution of dental implants on the
      load transmitted to the palate. MATERIAL AND METHODS: Eight implant analogues
      were placed in a replica of an average sized edentulous maxilla corresponding to
      the position of canines, first and second premolars, and first molars. The
      anteroposterior distance between the centers of implants in each quadrant was 8
      mm. Fifteen denture bases were fabricated to fit the edentulous maxilla analogue.
      The denture bases were attached to the oral analogue using 6 different
      configurations of attachments (6 groups): Either no Locator attachments were used
      (control group), or the 2 most anterior attachments were attached, or 4 implants
      were engaged with a distance of 8, 16, or 24 mm between the centers of implants
      on left and right side, and finally, when all 8 attachments were activated. A
      force-measuring sensor was used to measure the force transmitted to the palate
      when a static force of 245 N was applied on the occlusal rims of the denture
      bases. Data (Newtons) were analyzed using 1-way ANOVA and Tukey's HSD test
      alpha=.05). RESULTS: The mean (SD) amount of force measured on the palate when
      the overdentures were supported by 4 Locator attachments; [49.84 (26.52) at 8 mm
      spacing], [24.42 (15.05) at 16 mm spacing], [35.66 (22.94) at 24 mm spacing] was
      significantly lower than when no attachments [90.98 (20.20), control], or when 2
      Locator attachments were used [76.07 (27.63)] (P<.001). When the overdentures
      were supported by 8 Locator attachments, the force measured on the palate
      [20.67(16.06) N] was significantly lower than that for the control group
      (P<.001), overdentures supported by 2 Locator attachments (P<.001), and
      overdentures supported by 4 Locator attachments when the distance between the
      anterior and posterior implants was 8 mm P=.006). CONCLUSIONS: The distribution
      of implants had a significant effect on the force measured on the palate of the
      oral analogue in overdentures retained by Locator attachments. When the distance
      between the 4 implants was 16 or more mm, the load was not significantly lower
      than the 8 implant design, suggesting that the palate of a 4 implant-retained
      overdenture with a distance of 16 mm or more, does not contribute significantly
      to the load transfer to underlying hard palate in the in vitro analogue
      evaluated.

PMID- 22633592
TI  - Differences in implant stability associated with various methods of preparation
      of the implant bed: an in vitro study.
AB  - STATEMENT OF PROBLEM: It is difficult to achieve the primary stability necessary
      for immediate loading in the posterior maxilla because of thin cortical bone, low
      density trabecular bone, and inadequate bone height due to the presence of the
      maxillary sinus. PURPOSE: The purpose of this study was to examine the primary
      stability of dental implants placed by using different methods of preparation for
      in vitro monocortical and bicortical models of the posterior maxilla. MATERIAL
      AND METHODS: Sixty screw-shaped implants (4.0 * 10 mm) were inserted into solid
      rigid polyurethane blocks. The implants were divided into 6 groups (n=10) to test
      2 variables: 1) location (monocortical or bicortical block) and 2) preparation
      method (standard preparation, underpreparation, or the osteotome technique). The
      insertion and removal torques were measured and resonance frequency analysis
      (RFA) was performed to determine the primary stability of each implant. Insertion
      and removal torque data were analyzed by 2-way ANOVA, followed by the post hoc
      Tukey HSD multiple comparison test. RFA data were analyzed by 2-way and 1-way
      ANOVAs and the Tukey HSD multiple comparison test (alpha=.05). The Pearson
      correlation analysis was also performed to examine correlations among the values.
      RESULTS: The preparation method had a significant effect on insertion torque, RFA
      value, and removal torque; however location had a significant effect only on the
      removal torque (P<.001). There was a significant interaction between location and
      preparation method for RFA values (P=.045) and a significant difference in
      standard preparation method according to the location (P=.039); however, there
      was no significant difference in underpreparation (P=1.00) and osteotome
      technique (P=1.00). Statistically significant correlations were found between
      insertion torque and RFA values (r=0.529, P< .001), insertion torque and removal
      torque values (r=0.517, P< .001), and removal torque and RFA values (r=0.481,
      P<.001). CONCLUSIONS: Underpreparation and bicortical fixation significantly
      increased implant stability and the osteotome technique decreased implant
      stability in synthetic bone models that mimicked the posterior maxillary region.
      The primary stability values had statistically significant correlations to each
      other.

PMID- 22633593
TI  - A prospective evaluation of zirconia posterior fixed dental prostheses: three
      year clinical results.
AB  - STATEMENT OF PROBLEM: Although the favorable mechanical properties of zirconium
      oxide-based ceramics have increased the acceptance of fixed dental prostheses for
      use in the posterior regions of the mouth in recent years, there are few clinical
      studies documenting the longevity of these restorations. Furthermore, certain
      complications must be resolved before the material is used more extensively.
      PURPOSE: The purpose of this randomized prospective study was to evaluate the
      clinical performance of zirconia (Lava) 3-unit posterior fixed dental prostheses.
      MATERIAL AND METHODS: Twenty 3-unit fixed dental prostheses were placed in 17
      participants to replace a second premolar or a first molar. Eleven were placed in
      the maxilla and 9 in the mandible. All abutment teeth were prepared with a
      chamfer finish line of 0.8 to 1 mm, and frameworks were prepared with the Lava
      system. Restorations were cemented with a resin cement. Two calibrated examiners
      independently evaluated the fixed dental prostheses 1 week (baseline) and 1, 2,
      and 3 years after placement with the California Dental Association quality
      evaluation system. The periodontal parameters: the gingival index, plaque index,
      margin index, and the probing depths of abutment teeth and contralateral teeth
      were assessed. Data were analyzed by using descriptive statistics and the
      Wilcoxon signed-rank test (alpha=.05). RESULTS: All fixed dental prostheses were
      rated satisfactory after 3 years, and no fracture of the framework was observed
      during the observation period. One fixed dental prostheses was lost because of a
      biological complication at the 3-year examination, and a small degree of chipping
      of the veneering ceramic was observed in 2 participants. No significant
      differences among the periodontal parameters of the test and control teeth were
      observed except for the margin index. CONCLUSIONS: The results of a 3-year
      evaluation suggest that posterior zirconia 3-unit fixed dental prostheses are a
      reliable treatment.

PMID- 22633594
TI  - Evaluation of a conditioning method to improve core-veneer bond strength of
      zirconia restorations.
AB  - STATEMENT OF PROBLEM: The high strength and fracture toughness of zirconia have
      supported its extensive application in esthetic dentistry. However, the
      fracturing of veneering porcelains remains one of the primary causes of failure.
      PURPOSE: The purpose of this study was to evaluate, with shear bond strength
      testing, the effect of a simple and novel surface conditioning method on the core
      veneer bond strength of a zirconia ceramic system. MATERIAL AND METHODS: The
      shear bond strength of a zirconia core ceramic to the corresponding veneering
      porcelain was tested by the Schmitz-Schulmeyer method. Thirty zirconia core
      specimens (10 * 5 * 5 mm) were layered with a veneering porcelain (5 * 3 * 3 mm).
      Three different surface conditioning methods were evaluated: polishing with up to
      1200 grit silicon carbide paper under water cooling, airborne-particle abrasion
      with 110 MUm alumina particles, and modification with zirconia powder coating
      before sintering. A metal ceramic system was used as a control group. All
      specimens were subjected to shear force in a universal testing machine at a
      crosshead speed of 0.5 mm/min. The shear bond strength values were analyzed with
      1-way ANOVA and Tukey's post hoc pairwise comparisons (alpha=.05). The fractured
      specimens were examined with a scanning electron microscope to observe the
      failure mode. RESULTS: The mean (SD) shear bond strength values in MPa were 47.02
      (6.4) for modified zirconia, 36.66 (8.6) for polished zirconia, 39.14 (6.5) for
      airborne-particle-abraded zirconia, and 46.12 (7.1) for the control group. The
      mean bond strength of the control (P=.028) and modified zirconia groups (P=.014)
      was significantly higher than that of the polished zirconia group. The airborne
      particle-abraded group was not significantly different from any other group.
      Scanning electron microscopy evaluation showed that cohesive fracture in the
      veneering porcelain was the predominant failure mode of modified zirconia, while
      the other groups principally fractured at the interface. CONCLUSIONS: Modifying
      the zirconia surface with powder coating could significantly increase the shear
      bond strength of zirconia to veneering porcelain.

PMID- 22633595
TI  - A comparison of pressure generated by cordless gingival displacement techniques.
AB  - STATEMENT OF PROBLEM: Handling properties of cordless gingival displacement
      materials is not well understood, resulting in incorrect use. Insufficient
      displacement of the gingival margin may result in a poor impression. PURPOSE:
      This study investigated the pressure generated by a cordless displacement paste
      with respect to different techniques. MATERIAL AND METHODS: Two chambers with
      dimensions of 5 * 5 * 2 mm were made from Type IV stone and silicone material to
      simulate a rigid and elastic environment. A pressure gage was embedded into the
      wall of the chamber, and a paste material (Expasyl) was injected into the
      different chambers. The final pressures generated by the Expasyl were recorded by
      Chart 5 software and Power Lab system. This was repeated by using a displacement
      cord (KnitTrax) as a control for the study. The different loading methods for the
      Expasyl material were compared with 1-way ANOVA (alpha=.05). RESULTS: The mean
      pressure generated during placement of the Expasyl paste material in the silicone
      chamber was 143 kPa, which is significantly lower (P=.001) than the pressure
      generated by the KnitTrax cord (5396 kPa). Manipulating Expasyl after placement
      resulted in a pressure reduction of 73% in the stone chamber and 29% in the
      silicone chamber. CONCLUSIONS: Pressure generated by Expasyl is minimal compared
      to the cord system. Pressure is generated during the injection of the Expasyl,
      and subsequent manipulation reduced the final pressure. Handheld and motorized
      delivery guns produce similar pressure, but the motorized gun was found to have a
      more constant pressure delivery.

PMID- 22633597
TI  - Correlating the curve distance between the distal of the canines to the combined
      width of the six anterior teeth when selecting denture teeth for different ethnic
      groups.
AB  - STATEMENT OF PROBLEM: To select the width of denture teeth, the distance between
      the marks indicating the location of the canines is usually measured around the
      curvature of the wax occlusal rim; however, most manufacturers' mold charts
      provide the measurements of the artificial 6 anterior teeth as if they were on a
      straight line. PURPOSE: The purpose of this study was to investigate whether the
      curve distance between the distal surfaces of the maxillary canines can be
      related to the combined width (straight measurement) of the 6 anterior teeth in 4
      ethnic groups. MATERIAL AND METHODS: Maxillary stone casts were obtained for 160
      dentate subjects of 4 ethnic groups (40 whites, 40 blacks, 40 multiracial -
      descendants of white and black parents, and 40 Asians). The width of each
      maxillary anterior tooth was measured on the casts with sliding calipers. The
      combined width of the 6 anterior teeth (CW) corresponded to the sum of the width
      of each anterior tooth. The curve distance between the distal surfaces of the
      canines (CD) was measured by using dental tape and sliding calipers. The Pearson
      correlation coefficient and regression analysis were used to evaluate the
      relationship between CD and CW in each ethnic group (alpha=.05). RESULTS: The
      mean CD and CW values (in mm) obtained were: whites (CD=52.12; CW=45.65); blacks
      (CD=56.10; CW=48.13); multiracial (CD=53.58; CW=46.54); and Asians (CD=53.29;
      CW=46.60). Significant (P<.001) correlations between CD and CW measurements were
      observed for all ethnic groups studied (whites, r=0.957; blacks, r=0.803;
      multiracial, r=0.917; and Asians, r=0.881). The following linear regression
      equations were obtained: whites [CD=1.1(CW)+0.3]; blacks [CD=0.95(CW)+9.3];
      multiracial [CD=1.2(CW)-1.1]; and Asians [CD=1.0(CW)+5]. CONCLUSIONS: The curve
      distance between the distal surfaces of the maxillary canines can be accurately
      related to the combined width of the 6 anterior teeth in the selection of denture
      teeth for the studied ethnic groups.

PMID- 22633596
TI  - Fabrication of titanium removable dental prosthesis frameworks with a 2-step
      investment coating method.
AB  - STATEMENT OF PROBLEM: Although pure titanium is known to have good
      biocompatibility, a titanium alloy with better strength is needed for fabricating
      clinically acceptable, partial removable dental prosthesis (RDP) frameworks.
      PURPOSE: The mechanical properties of an experimental Ti-5Al-5Cu alloy cast with
      a 2-step investment technique were examined for RDP framework applications.
      MATERIAL AND METHODS: Patterns for tests for various properties and denture
      frameworks for a preliminary trial casting were invested with a 2-step coating
      method using 2 types of mold materials: a less reactive spinel compound
      (Al(2)O(3).MgO) and a less expensive SiO(2)-based material. The yield and tensile
      strength (n=5), modulus of elasticity (n=5), elongation (n=5), and hardness (n=8)
      of the cast Ti-5Al-5Cu alloy were determined. The external appearance and
      internal porosities of the preliminary trial castings of denture frameworks (n=2)
      were examined with a conventional dental radiographic unit. Cast Ti-6Al-4V alloy
      and commercially pure titanium (CP Ti) were used as controls. The data for the
      mechanical properties were statistically analyzed with 1-way ANOVA (alpha=.05).
      RESULTS: The yield strength of the cast Ti-5Al-5Cu alloy was 851 MPa and the
      hardness was 356 HV. These properties were comparable to those of the cast Ti-6Al
      4V and were higher than those of CP Ti (P<.05). One of the acrylic resin
      retention areas of the Ti-5Al-5Cu frameworks was found to have been incompletely
      cast. CONCLUSIONS: The cast biocompatible experimental Ti-5Al-5Cu alloy exhibited
      high strength when cast with a 2-step coating method. With a dedicated study to
      determine the effect of sprue design on the quality of castings, biocompatible Ti
      5Al-5Cu RDP frameworks for a clinical trial can be produced.

PMID- 22633598
TI  - Complete arch implant impression technique.
AB  - When making a definitive impression for an arch containing multiple implants,
      there are many reported techniques for splinting impression copings. This article
      introduces a splint technique that uses the shim method, which has been
      demonstrated to reduce laboratory and patient chair time, the number of
      impression copings and laboratory analogs needed, and the ultimate cost.

PMID- 22633599
TI  - A simple technique to fabricate an implant counter torque device.

PMID- 22633602
TI  - A case of acute thrombotic occlusion of an anomalous origin of the right coronary
      artery from the left coronary sinus: focus on the importance of dual-source
      computed tomography for failed emergency coronary angiography.
AB  - Coronary artery anomalies in patients undergoing coronary angiography are often
      technically challenging for invasive cardiologists and may delay
      revascularization time. We report a patient who underwent successful bailout
      revascularization using dual-source computed tomography after failed emergency
      angiography. This case emphasizes the utility of dual-source computed tomography,
      especially in an urgent clinical setting, for allowing interventional
      cardiologists to rapidly identify and effectively treat the aberrant coronary
      artery.

PMID- 22633601
TI  - A low-fat dietary pattern and risk of metabolic syndrome in postmenopausal women:
      the Women's Health Initiative.
AB  - OBJECTIVE: Nutrition plays an important role in metabolic syndrome etiology. We
      examined whether the Women's Health Initiative (WHI) Dietary Modification Trial
      influenced metabolic syndrome risk. MATERIALS/METHODS: 48,835 postmenopausal
      women aged 50-79 years were randomized to a low-fat (20% energy from fat) diet
      (intervention) or usual diet (comparison) for a mean of 8.1 years. Blood
      pressure, waist circumference and fasting blood measures of glucose, HDL
      cholesterol and triglycerides were measured on a subsample (n=2816) at baseline
      and years 1, 3 and 6 post-randomization. Logistic regression estimated
      associations of the intervention with metabolic syndrome risk and use of
      cholesterol-lowering and hypertension medications. Multivariate linear regression
      tested associations between the intervention and metabolic syndrome components.
      RESULTS: At year 3, but not years 1 or 6, women in the intervention group (vs.
      comparison) had a non-statistically significant lower risk of metabolic syndrome
      (OR=0.83, 95%CI 0.59-1.18). Linear regression models simultaneously modeling the
      five metabolic syndrome components revealed significant associations of the
      intervention with metabolic syndrome at year 1 (p<0.0001), but not years 3
      (p=0.19) and 6 (p=0.17). Analyses restricted to intervention-adherent
      participants strengthened associations at years 3 (p=0.05) and 6 (p=0.06).
      Cholesterol-lowering and hypertension medication use was 19% lower at year 1 for
      intervention vs. comparison group women (OR=0.81, 95% CI 0.60-1.09).Over the
      entire trial, fewer intervention vs. comparison participants used these
      medications (26.0% vs. 29.9%), although results were not statistically
      significant (p=0.89). CONCLUSIONS: The WHI low-fat diet may influence metabolic
      syndrome risk and decrease use of hypertension and cholesterol-lowering
      medications. Findings have potential for meaningful clinical translation.

PMID- 22633600
TI  - Recruitment and retention dynamics of RECQL5 at DNA double strand break sites.
AB  - RECQL5 is one of the five human RecQ helicases, involved in the maintenance of
      genomic integrity. While much insight has been gained into the function of the
      Werner (WRN) and Bloom syndrome proteins (BLM), little is known about RECQL5. We
      have analyzed the recruitment and retention dynamics of RECQL5 at laser-induced
      DNA double strand breaks (DSBs) relative to other human RecQ helicases. RECQL5
      depleted cells accumulate persistent 53BP1 foci followed by gamma-irradiation,
      indicating a potential role of RECQL5 in the processing of DSBs. Real time
      imaging of live cells using confocal laser microscopy shows that RECQL5 is
      recruited early to laser-induced DSBs and remains for a shorter duration than BLM
      and WRN, but persist longer than RECQL4. These studies illustrate the
      differential involvement of RecQ helicases in the DSB repair process. Mapping of
      domains within RECQL5 that are necessary for recruitment to DSBs revealed that
      both the helicase and KIX domains are required for DNA damage recognition and
      stable association of RECQL5 to the DSB sites. Previous studies have shown that
      MRE11 is essential for the recruitment of RECQL5 to the DSB sites. Here we show
      that the recruitment of RECQL5 does not depend on the exonuclease activity of
      MRE11 or on active transcription by RNA polymerase II, one of the prominent
      interacting partners of RECQL5. Also, the recruitment of RECQL5 to laser-induced
      damage sites is independent of the presence of other DNA damage signaling and
      repair proteins BLM, WRN and ATM.

PMID- 22633603
TI  - Alpinetin/hydroxypropyl-beta-cyclodextrin host-guest system: preparation,
      characterization, inclusion mode, solubilization and stability.
AB  - The inclusion complexation behavior, characterization and binding ability of
      alpinetin with hydroxypropyl-beta-cyclodextrin (HPbetaCD) has been investigated
      in both solution and the solid state by means of UV-vis spectroscopy, FT-IR, 1H
      and 2D NMR, XRD, SEM and DSC. The results showed that the water solubility and
      stability of alpinetin were obviously increased in the inclusion complex with
      HPbetaCD. This satisfactory water solubility and high stability of the
      alpinetin/HPbetaCD complex will be potentially useful for its application as
      herbal medicine or healthcare products.

PMID- 22633604
TI  - A multidisciplinary approach for the analysis of an adulterated dietary
      supplement where the active pharmaceutical ingredient was embedded in the capsule
      shell.
AB  - Fourier transform infrared (FT-IR) microspectroscopic imaging, Raman
      microspectroscopy, optical microscopy and high performance liquid chromatography
      with mass spectrometric (LC/MS) detection were employed to examine a dietary
      supplement adulterated with an undeclared active pharmaceutical ingredient (API).
      While a trace level of the API was detected in the capsule contents, a higher
      concentration of API was found in the capsule shell, which indicated the use of
      an unconventional manufacturing process to hide the API and thus avoid detection.
      This study demonstrates the need for a multidisciplinary approach to provide a
      complete assessment of a suspect adulterated dietary supplement.

PMID- 22633605
TI  - Characterization of currently marketed heparin products: analysis of heparin
      digests by RPIP-UHPLC-QTOF-MS.
AB  - Previously, the FDA validated a method to assess the structure and composition of
      heparin products by separating and quantifying disaccharide level digests by
      reverse-phase-ion-pairing liquid chromatography (RPIP-HPLC) coupled to a low
      resolution and low sensitivity ion trap mass-spectrometer. Here, improved
      separation, information content and sensitivity were obtained through the use of
      reverse phase ion-pairing ultra-high pressure liquid chromatography (RPIP-UHPLC)
      coupled with a quadrupole time-of-flight (Q-TOF) mass spectrometer. Thus, with
      the new method, improved structural characterization of the same 20 lots of
      heparin sodium active pharmaceutical ingredients (APIs) as were analyzed in the
      previous work were obtained. In addition, for the first time, 10 low molecular
      weight heparin (LMWH) lots were characterized representing multiple lots
      manufactured by three different processes (dalteparin, tinzaparin or enoxaparin).
      In this study, UHPLC separation conditions and the enzymatic digesting protocol
      were optimized for analysis of disaccharide level digests of heparin and positive
      and negative electrospray ionization (ESI) modes were tested. The negative ion
      mode ESI analysis was found to be superior to the positive ion mode for these
      measurements, and a combination of heparin lyase II and III were optimal for
      heparin digestion. The data obtained establishes the normal variation in the
      composition of heparin sodium or LMWHs in this assay. These values are useful as
      possible product benchmarks and for surveillance of the heparin products being
      imported into the US market.

PMID- 22633606
TI  - Survey of several methods deproteinizing human plasma before and within the
      chloroformate-mediated treatment of amino/carboxylic acids quantitated by gas
      chromatography.
AB  - Trichloroacetic acid, perchloric acid, phosphotungstic acid, acetonitrile,
      methanol and some other organic solvents were evaluated for their ability to
      provide protein and lipid-free plasma supernatants. The residual proteins, total
      cholesterol and triacylglycerols were assayed in the supernatant on a Beckman
      Analyzer instrument. The free cholesterol and the neutral lipids were further
      analyzed by means of high-temperature GC analysis. The conditions for the
      deproteinizing step were optimized for minimal lipoprotein disruption. A
      substantial difference regarding contamination by the lipids was found if the
      plasma supernatant or the whole serum were treated with an alkyl chloroformate
      reagent. Three plasma sulfur amino acids and the aromatic ones were chosen as
      model compounds to evaluate compatibility of the precipitation methods with a
      subsequent methyl chloroformate-mediated derivatization and GC-MS analysis. The
      results of the total homocysteine assay matched well with that obtained using a
      commercial immunoassay. Precipitation with trichloroacetic acid has proven to be
      a method of choice for the analysis of the acido-basic analytes by GC-MS via
      chloroformates.

PMID- 22633607
TI  - [The tear biomarkers, as source of information for the ocular surface. the tears
      as mirror of the eye?].

PMID- 22633608
TI  - [Influence of pregnancy on refractive parameters after LASIK surgery].
AB  - OBJECTIVES: Different ocular changes and complications of refractive surgery such
      as photorefractive keratectomy (PRK) due to pregnancy have been described in the
      last few years. However there is no information about the possible problems of
      laser in situ keratomileusis (LASIK) in pregnant women. Our objective was to
      study how physiological changes secondary to pregnancy could alter the refractive
      situation in pregnant women who have undergone LASIK surgery. We show the results
      obtained due to the changes between the first two trimesters of the pregnancy.
      METHODS: A prospective and observational study was conducted in which one study
      group, made up of 9 patients who had undergone LASIK surgery before becoming
      pregnant, was compared with a control group of 9 patients with non-surgically
      corrected refractive problems. The following measurements were made in both
      groups in the first and second trimesters of the pregnancy; visual acuity, the
      best corrected visual acuity, tonometry, ocular anatomical characteristics by
      biometry, and refractive and corneal study by Pentacam((r)). RESULTS: Signicant
      changes were observed in the cylinder and spherical equivalent between the two
      trimesters in both groups. Visual acuity and spherical equivalent show a strong
      trend towards worsening, which was more significant in the study group. The
      patients of this group who had a larger pre-surgical defect showed lower
      modifications during the six first months of pregnancy. CONCLUSIONS: The majority
      of women who require laser refractive surgery are are between 20-30 years old,
      thus in many cases corneal surgery is followed by at least one pregnancy, with
      different possible ophthalmological effects. The conclusions that may be derived
      from this study are that the assessment of the refractive changes in surgically
      operated corneas may be biomechanically weakened on being subjected to
      physiological hormone stimulation as happens during gestation.

PMID- 22633609
TI  - [Crystalline keratopathy in pterigium treatment: case report].
AB  - CASE REPORT: A 65 year-old female who consulted due to the emergence of a white
      spot in the eye that had grown over the last year. The physical examination
      showed an intrastromal white crystal-like infiltrate and a tree-like morphology,
      with minimal inflammatory response. It was treated topically with no clear
      improvement, requiring a penetrating keratoplasty. DISCUSSION: A crystalline
      keratopathy is a rare event and characteristic of, but not exclusively, to a
      Streptococcus viridans infectious keratitis. It has been associated with
      prolonged use of topical steroids after penetrating keratoplasty and usually has
      a poor response to treatment.

PMID- 22633610
TI  - [Siderosis bulbi. Clinical presentation of a case of three years from onset].
AB  - CASE REPORT: The clinical and functional characteristics of a 30 years-old
      patient with three years-evolution siderosis bulbi are described in this paper,
      as well as the treatment using phacoemulsification and vitrectomy for the
      elimination of the metallic remains. DISCUSSION: In spite of the fact that the
      majority of the intraocular foreign bodies (IOFB) have a dangerous immediate
      effect, in cases of small, local bodies and with little visual deterioration,
      observation is possible. Nevertheless, with time, the iron settles on the
      pigmented epithelium of the retina, producing changes at macula and peripheral
      level, which are responsible for the gradual loss of vision. The surgical removal
      of the IOFB can stop the progression of this pathology.

PMID- 22633611
TI  - [Pseudo-vitelliform maculopathy and bilateral choroidal folds: differential
      diagnosis].
AB  - CLINICAL CASE: A 64 year old woman. Best corrected acuity right eye (RE) 0.5 and
      0.7 left eye (LE). Bilateral pseudophakia. No inflammatory signs. Normal IOP. RE
      fundus showed a rounded, yellow and excessive subfoveal deposit with positive
      autofluorescence. Multiple equatorial drusen and choroidal folds in both eyes.
      Fluorescein angiography of RE showed early foveal hypofluorescence and delayed
      hyperluorescence. Optical coherence tomography revealed a hiperreflective deposit
      over the foveal epithelium pigment. Visual fields, ocular ultrasounds and
      electrooculograms were normal. Non-specific alterations in colour tests.
      CONCLUSION: Vitelliform maculopathy and choroidal folds are very rare diseases
      and, exceptionally, appear together.

PMID- 22633612
TI  - [Ozurdex((r)) and aphakia: a combination to avoid].

PMID- 22633613
TI  - [Eye pathology in the paintings by Rafael Sanzio (I). Portrait of Tommaso
      Inghirami].

PMID- 22633614
TI  - [Percy Lavon Julian. Montgomery - Alabama, USA. (1899)-Waukegan - Illinois, USA.
      (1975)].

PMID- 22633615
TI  - Phenotypic findings in Chinese families with X-linked hypohydrotic ectodermal
      dysplasia.
AB  - OBJECTIVE: To summarize the phenotypic characters of Chinese X-linked
      hypohidrotic ectodermal dysplasia (XLHED) subjects. DESIGN: Twelve affected and
      24 carriers from seven Chinese pedigrees were recruited. The development of their
      hair, tooth, skin and sweat gland was (semi-)quantitatively evaluated. From 100
      to 250 normal controls were used to exclude polymorphisms in each family.
      RESULTS: Different from the previous reports, these Chinese subjects had more
      symmetrical and severe oligodontia. The mean number of permanent teeth missing
      was 23.5, and mandibular molars were preferentially affected. Compared to the age
      and gender-matching controls, the affected had evident deep and well-defined
      facial wrinkles especially in the forehead, periorbital and cheek. Missing
      anterior teeth, conical canines and slow growth of hair were the main findings of
      female carriers. In addition, there was no evident relationship between phenotype
      and genotype. CONCLUSIONS: To the best of our knowledge, this was the first semi
      quantitative phenotypic report of subjects of Chinese descent.

PMID- 22633616
TI  - Benzodiazepine-induced spatial learning deficits in rats are regulated by the
      degree of modulation of alpha1 GABA(A) receptors.
AB  - Despite significant advances in understanding the role of benzodiazepine (BZ)
      sensitive populations of GABAA receptors, containing the alpha1, alpha2, alpha3
      or alpha5 subunit, factual substrates of BZ-induced learning and memory deficits
      are not yet fully elucidated. It was shown that alpha1-subunit affinity-selective
      antagonist beta-CCt almost completely abolished spatial learning deficits induced
      by diazepam (DZP) in the Morris water maze. We examined a novel, highly (105
      fold) alpha1-subunit selective ligand-WYS8 (0.2, 1 and 10 mg/kg), on its own and
      in combination with the non-selective agonist DZP (2 mg/kg) or beta-CCt (5 mg/kg)
      in the water maze in rats. The in vitro efficacy study revealed that WYS8 acts as
      alpha1-subtype selective weak partial positive modulator (40% potentiation at
      100nM). Measurement of concentrations of WYS8 and DZP in rat serum and brain
      tissues suggested that they did not substantially cross-influence the respective
      disposition. In the water maze, DZP impaired spatial learning (acquisition
      trials) and memory (probe trial). WYS8 caused no effect per se, did not affect
      the overall influence of DZP on the water-maze performance and was devoid of any
      activity in this task when combined with beta-CCt. Nonetheless, an additional
      analysis of the latency to reach the platform and the total distance swam
      suggested that WYS8 addition attenuated the run-down of the spatial impairment
      induced by DZP at the end of acquisition trials. These results demonstrate a
      clear difference in the influence of an alpha1 subtype-selective antagonist and a
      partial agonist on the effects of DZP on the water-maze acquisition.

PMID- 22633617
TI  - Time to all-cause treatment discontinuation of olanzapine compared to other
      antipsychotics in the treatment of schizophrenia: a systematic review and meta
      analysis.
AB  - OBJECTIVE: This comprehensive review and meta-analysis compared the effectiveness
      of olanzapine and other antipsychotics in schizophrenia treatment, defining
      effectiveness as time to all-cause medication discontinuation (primary) and as
      all-cause treatment discontinuation rates. This study examined randomized
      clinical trials (RCTs) and observational non-interventional studies. EXPERIMENTAL
      PROCEDURES: Schizophrenia studies that compared olanzapine with individual first-
      (FGAs) and/or second-generation antipsychotics (SGAs) were included in the meta
      analyses. Hazard ratios (HR), risk ratios (RR), and their associated 95%
      confidence intervals were extracted for RCTs and observational studies.
      Sensitivity analyses assessed the impact of sources of funding, dose of
      olanzapine, and allocation concealment method on final results. RESULTS: There
      were 60 RCTs (N=33,360) and 27 observational studies (N=202,591) included. On
      time to all-cause medication discontinuation, olanzapine was significantly better
      than aripiprazole, quetiapine, risperidone, ziprasidone and perphenazine for RCTs
      and better than amisulpride, risperidone, haloperidol, and perphenazine for
      observational studies. There were no significant differences between olanzapine
      and clozapine in RCTs or observational studies. All-cause discontinuation rates
      in RCTs were significantly lower for olanzapine compared to all comparators
      except amisulpride and clozapine. In observational studies, olanzapine was less
      effective than clozapine. Industry-sponsored studies favored olanzapine when
      compared to haloperidol and perphenazine; higher dose of olanzapine favored
      quetiapine and perphenazine when compared to olanzapine; method of allocation
      concealment did not generally affect the results. CONCLUSION: Using a global
      measure of medication effectiveness (time to all-cause medication
      discontinuation), olanzapine appears to be more effective - in both RCTs and
      observational studies - than most SGAs and FGAs, except for clozapine.

PMID- 22633618
TI  - Formula to predict platelet count after partial splenic arterial embolization in
      patients with hypersplenism.
AB  - PURPOSE: To establish a formula to guide appropriate embolization volume for
      postprocedural platelet gain following partial splenic arterial embolization
      (PSE) for hypersplenism. MATERIALS AND METHODS: The hepatic volume (Vh) and
      splenic volume (Vsp) were measured by using 2-mm-thick computed tomography images
      before and after PSE in 20 patients with various chronic liver diseases. A
      formula was derived from the relationship between the platelet count increase
      ratio (dPlt%) and the organ volumes, which was then evaluated in another cohort.
      RESULTS: After an embolization of a median of 72.1% of the spleen (interquartile
      range, 38.2%-93.8%), the dPlt% was 67.7% +/- 40.0 and significantly correlated
      with the increasing ratio of Vh to Vsp (P = .019, rho = 0.52). Because the
      difference in Vh/Vsp ratio after PSE was significantly correlated with the spleen
      embolization ratio (eVsp%; P = .0003, rho = 0.72), the estimated dPlt% could be
      derived from the Vh/Vsp ratio before PSE and the eVsp%. The estimated dPlt% was
      significantly correlated with the actual dPlt% (P = .0003, rho = 0.72). When the
      formula was evaluated in another cohort of 14 cases, another strict correlation
      was observed (P < .0001, rho = 0.92). CONCLUSIONS: These data suggest that
      platelet count after PSE can be predicted before the procedure by using the
      Vh/Vsp ratio and the anticipated spleen embolization volume. The use of such a
      prediction can prevent too much or too little embolization, thereby leading to an
      improvement in the risk/return trade-off in PSE.

PMID- 22633619
TI  - Indirect computed tomography venography of the lower extremities using single
      source dual-energy computed tomography: advantage of low-kiloelectron volt
      monochromatic images.
AB  - PURPOSE: To study the performance of dual-energy indirect computed tomography
      (CT) venography from single-source dual-energy CT in the assessment of lower
      extremity deep venous thrombosis (DVT). MATERIALS AND METHODS: In a retrospective
      study, 110 patients suspected to have pulmonary embolism (PE) underwent dual
      energy CT venography on a single-source dual-energy CT scanner as a part of CT
      pulmonary angiography protocol at 3 minutes after injection of contrast material.
      Two radiologists evaluated 50-kiloelectron volt (keV) and 70-keV monochromatic
      images reconstructed from a dual-energy CT scan for image quality, image noise,
      venous contrast, and confidence level in interpretation for DVT using a scale of
      1-5. In addition, a combined 50-keV and 70-keV data set was assessed for
      confidence level in image interpretation. Attenuation, contrast-to-noise ratio
      (CNR), and objective noise were measured in bilateral common femoral and
      popliteal veins. Data were analyzed using Student t test and Wilcoxon rank sum
      test. Radiation dose was measured for dual-energy CT venography protocol.
      RESULTS: A diagnosis of DVT was made in 8 of 110 patients (7.27%). The subjective
      image quality was comparable between 50-keV and 70-keV images (4.3 vs 4.5; P >
      .05). The subjective venous contrast opacification (4.7 vs 3.5; P = .0036) and
      confidence (4.8 vs 3.9; P = .0028) in image interpretation were superior at 50
      keV. Confidence level for interpretation on combined 50-keV and 70-keV series
      (score 4.7) was similar to that for 50-keV series (score 4.8). Compared with 70
      keV data, 50-keV data yielded 90% increase in intravascular CT attenuation (207.4
      Hounsfield units [HU] +/- 39.0 vs 106.8 HU +/- 7.6; P <.0001) and higher CNR
      (10.7 +/- 4.07 vs 7.2 +/- 4.1; P = .0001) of the deep veins. However, objective
      noise at 50 keV was higher (14.8 HU vs 6.5 HU; P = .0031). Because of inadequate
      contrast opacification, 6% of CT venography studies were deemed suboptimal for
      rendering a diagnostic interpretation on 70-keV images, but these images were
      considered acceptable at 50 keV. The mean effective radiation dose for the dual
      energy CT venography examination was 4.2 mSv. CONCLUSIONS: Optimal image quality
      with substantially higher venous attenuation is provided by 50-keV monochromatic
      images from dual-energy CT venography acquisition compared with 70-keV images.
      The 50-keV monochromatic images increase the confidence in the image
      interpretation of DVT and decrease the number of indeterminate studies.

PMID- 22633620
TI  - Dilation of the renal artery in an infant: 5 years later.

PMID- 22633621
TI  - Clinical utility of des-gamma-carboxyprothrombin kinetics as a complement to
      radiologic response in patients with hepatocellular carcinoma undergoing
      transarterial chemoembolization.
AB  - PURPOSE: Serial alpha-fetoprotein (AFP) measurements are useful for assessing
      tumor responses to numerous therapies for hepatocellular carcinoma (HCC). This
      study tested the predictive value of changes in des-gamma-carboxy prothrombin
      (DCP), in parallel with AFP, as an indicator of HCC response after transarterial
      chemoembolization. MATERIALS AND METHODS: The study group consisted of 327
      patients with HCC initially seropositive for DCP (>= 40 mAU/mL) and/or AFP (>=
      100 ng/mL) who underwent repeated chemoembolization as first-line therapy.
      Radiologic responses were measured based on modified Response Evaluation Criteria
      In Solid Tumors guidelines. Serologic response was defined as a decrease of at
      least 50% in DCP or AFP level from baseline. Radiologic-serologic correlation and
      disease progression and survival according to serologic responses were analyzed.
      RESULTS: Before treatment, 129 patients (39%) had high DCP alone, 66 (20%) had
      high AFP alone, and 58 (18%) had high levels of both. Radiologic and serologic
      responses were achieved in 88.2% and 91.4% of patients with high DCP levels and
      in 89.5% and 91.1% of those with high AFP levels, respectively. Serologic
      response based on AFP or DCP was significantly correlated with radiologic
      response, and this was confirmed by landmark analysis (P < .001). DCP and AFP
      responders had better times to progression and overall survival than
      nonresponders (P < .001). Cox models revealed that both serologic responses were
      independent estimates of survival (hazard ratios, 0.11 for DCP and 0.14 for AFP;
      P < .001). CONCLUSIONS: After transarterial chemoembolization for HCC, DCP
      response may be a useful surrogate endpoint of immediate and prolonged clinical
      outcomes, along with AFP response.

PMID- 22633622
TI  - Short-term effects of combined hepatic vein embolization and portal vein
      embolization for the induction of liver regeneration in a rabbit model.
AB  - PURPOSE: Alternative methods to optimize the hypertrophy response after portal
      vein embolization (PVE) are desired. This study assessed the effect of hepatic
      vein embolization (HVE) in addition to PVE on liver hypertrophy response in a
      standardized rabbit model. MATERIALS AND METHODS: Thirty rabbits were allocated
      to groups according to intervention: PVE alone, HVE alone, and a combination of
      HVE and PVE. The liver regeneration response of the nonembolized, caudal liver
      was assessed by computed tomographic volumetry, liver-to-body weight index, and
      the amount of proliferating hepatocytes. RESULTS: The caudal liver volume (CLV)
      increased significantly more in the PVE and combined PVE/HVE group than in the
      HVE group at 3 and 7 days after the procedure (P < .01). There were no
      significant differences in CLV increase or degree of hypertrophy between the PVE
      and combined embolization groups. The caudal liver-to-body weight index was
      significantly higher in the PVE and combined embolization groups than in the HVE
      group on day 7 (P < .01). The index was also significantly higher in the combined
      PVE/HVE group compared with the PVE group (P = .008). The caudal liver tissue of
      the PVE and combined groups contained a significantly higher number of
      proliferating hepatocytes compared with the HVE group on day 7 (P < .01).
      CONCLUSIONS: Although histologic and additional regenerative changes are seen,
      HVE in addition to PVE has no additional short-term effect on hypertrophy
      response. The combination of HVE and PVE may therefore have little use in a
      clinical setting.

PMID- 22633623
TI  - Minimising the risk of accidental dural puncture with epidural analgesia for
      labour: a retrospective review of risk factors.
AB  - BACKGROUND: Accidental dural puncture has a quoted incidence of between 0.19% and
      3.6% of obstetric epidurals and is associated with significant morbidity. We set
      out to determine possible factors associated with an increased risk of accidental
      dural puncture. METHODS: We performed a retrospective review of 18385 epidurals,
      performed over a 15-year period. Factors analysed were: time of day of insertion,
      loss-of-resistance technique, maternal position, cervical dilatation, grade of
      anaesthetist and depth to the epidural space. RESULTS: Using univariate analyses
      we found no association between the risk of accidental dural puncture and the
      following variables: time of day of insertion (P=0.71), loss-of-resistance
      technique (P=0.22), maternal position for insertion (P=0.83), degree of cervical
      dilatation (P=0.41) and grade of anaesthetist performing the epidural (P=0.34).
      Conversely, we found that the risk of accidental dural puncture increased with
      increasing depth to the epidural space. This was confirmed using a logistic
      regression analysis, from which it was estimated that, for every 1-cm increase in
      depth, the risk of accidental dural puncture increased by approximately 19%
      (P=0.019; 95% CI for OR: 1.029-1.38). CONCLUSION: We conclude that the risk of
      accidental dural puncture increases with increasing depth to the epidural space.
      We suggest further study is required to correlate this risk with increasing body
      mass index.

PMID- 22633624
TI  - Phase II study of vinorelbine and continuous low doses cyclophosphamide in
      children and young adults with a relapsed or refractory malignant solid tumour:
      good tolerance profile and efficacy in rhabdomyosarcoma--a report from the
      Societe Francaise des Cancers et leucemies de l'Enfant et de l'adolescent (SFCE).
AB  - AIM: This phase II study evaluated efficacy, safety and pharmacokinetics (PK)
      profile of combination intravenous vinorelbine (VNL) and continuous low doses
      oral cyclophosphamide (CPM) combination in children and young adults with a
      recurrent or refractory solid tumour. METHODS: A total of 117 patients (median
      age, 12 years) within six disease strata received intravenous VNL 25mg/m(2) on
      days 1, 8 and 15 of each 28-day cycle combined with continuous daily oral CPM
      25mg/m(2). Tumour response was assessed every two cycles according to WHO (World
      Health Organisation) criteria. PK of VNL was investigated in a subset of 18
      patients aged 4-15 years. RESULTS: In rhabdomyosarcoma (RMS) (n=50), the best
      overall response rate (ORR) was 36% with four complete (8%) and 14 partial
      responses (28%). The best ORR was 13% in Ewing's sarcoma (n=15), 6% in non-RMS
      soft tissue sarcoma (n=16) and 6% in neuroblastoma (n=16). No response was
      observed in osteosarcoma (n=10) and medulloblastoma (n=7). The main grade 3/4
      toxicity was neutropenia (38%). Other severe toxicities were limited with 3% of
      peripheral neuropathy and no haemorrhagic cystitis. The PK analysis revealed
      equivalent blood exposure to VNL between children >4 years and adult series when
      the VNL dose was based on the body surface area-based dosing. CONCLUDING
      STATEMENT: In heavily pre-treated children, VNL combined with CPM showed an
      interesting response rate in RMS and an acceptable toxicity profile supporting
      further evaluation of these agents in phase III trials.

PMID- 22633625
TI  - Use of complementary and alternative medicine in breast cancer patients and their
      experiences: a cross-sectional study.
AB  - Complementary and Alternative Medicine (CAM) refers to various treatments not
      considered as part of conventional care. CAM is used by a high number of breast
      cancer patients. This is a cross-sectional study employing a validated
      questionnaire with the aim of studying CAM use and of exploring the needs of
      information and communication in female breast cancer patients. Experiences
      associated with discussing CAM within a conventional oncology setting were
      examined. Answers of patients not using CAM were also elicited. Predictors for
      CAM use were a higher degree of education and being of a younger age. The study
      demonstrated that patients were reluctant to initiate communication within
      standard oncology care. They rather relied on family and friends (49%), on the
      general practitioner (40%) or media sources (39%) for information. Reasons for
      not talking about CAM were not having been asked (25%) or not having perceived
      the inpatient physician to be the adequate person to talk to (11%). Reasons for
      not using CAM were mainly considering conventional therapy as sufficient (34%)
      and not having thought about CAM (31%). Particularly within conventional
      oncological care it is important to train physicians to have knowledge of
      supportive CAM options as this is what patients look for, but restrain from
      seeking within the speciality system.

PMID- 22633626
TI  - Impact of process parameters in the generation of novel aspirin nanoemulsions-
      comparative studies between ultrasound cavitation and microfluidizer.
AB  - In the present investigation, the operating efficiency of a bench-top air-driven
      microfluidizer has been compared to that of a bench-top high power ultrasound
      horn in the production of pharmaceutical grade nanoemulsions using aspirin as a
      model drug. The influence of important process variables as well as the pre
      homogenization and drug loading on the resultant mean droplet diameter and size
      distribution of emulsion droplets was studied in an oil-in-water nanoemulsion
      incorporated with a model drug aspirin. Results obtained show that both the
      emulsification methods were capable of producing very fine nanoemulsions
      containing aspirin with the minimum droplet size ranging from 150 to 170 nm. In
      case of using the microfluidizer, it has been observed that the size of the
      emulsion droplets obtained was almost independent of the applied
      microfluidization pressure (200-600 bar) and the number of passes (up to 10
      passes) while the pre-homogenization and drug loading had a marginal effect in
      increasing the droplet size. Whereas, in the case of ultrasound emulsification,
      the droplet size was generally decreased with an increase in sonication amplitude
      (50-70%) and period of sonication but the resultant emulsion was found to be
      dependent on the pre-homogenization and drug loading. The STEM microscopic
      observations illustrated that the optimized formulations obtained using
      ultrasound cavitation technique are comparable to microfluidized emulsions. These
      comparative results demonstrated that ultrasound cavitation is a relatively
      energy-efficient yet promising method of pharmaceutical nanoemulsions as compared
      to microfluidizer although the means used to generate the nanoemulsions are
      different.

PMID- 22633627
TI  - Rehabilitation for children after acquired brain injury: current and emerging
      approaches.
AB  - Evidence is emerging of diverse, chronic, cumulative disabilities experienced by
      children in the months and years after acquired brain injury. The long-held
      assumption that younger children recover better from brain injury than older
      children or adults has been challenged by recent studies. Populations with
      acquired brain injury include children with traumatic brain injury and stroke,
      and a proportion of children with cerebral palsy. Although characteristics of
      brain injury in children vary, subgroups of this population offer the potential
      to inform our understanding of developing brain structure-function relationships
      in response to intervention. Limited evidence and few controlled rehabilitation
      trials exist regarding children with neurologic conditions. A number of
      rehabilitation approaches produced benefits in adult stroke, and cerebral palsy
      populations may be applied to children with other acquired brain injuries.
      Rehabilitation approaches that have been applied to children with acquired brain
      injuries, or hold promise for future applications, are reviewed.

PMID- 22633628
TI  - Nonpharmacologic treatment of migraine with low-dose propranolol or
      amitriptyline.
AB  - This study evaluated the effectiveness of nonpharmacologic measures combined with
      low-dose propranolol or amitriptyline for treating severe pediatric migraine.
      Data were collected from the medical files of 118 patients (mean age, 12.54 +/-
      3.14 years S.D.). All were treated with nonpharmacologic measures. In addition,
      93 children received propranolol (mean initial dose, 0.4 +/- 0.17 mg/kg/day
      S.D.), and 25 received amitriptyline (mean initial dose, 0.26 +/- 0.1 mg/kg/day
      S.D.). Twenty patients were switched from propranolol to amitriptyline during
      treatment. In both groups, headache frequency was reduced by >50% per month in
      ~80% of patients. Patients without aura responded significantly better to
      propranolol than patients with aura (P = 0.02). No significant difference was
      evident in response to pharmacologic treatment by migraine frequency or type
      (episodic chronic). No significant difference was evident in response to
      amitriptyline between patients with or without aura. The response rate was higher
      than previously reported for placebo. Low-dose propranolol and low-dose
      amitriptyline, when combined with nonpharmacologic measures, are equally
      effective in reducing the frequency of migraine in children. Propranolol is
      preferred because of its lower risk of side effects. An additive effect of
      nonpharmacologic measures may allow for a reduction in drug dose.

PMID- 22633629
TI  - Adaptive behavior outcomes in infants treated with adjunctive topiramate.
AB  - Data from two global studies (6-week open-label, phase 1 study; 20-day double
      blind, phase 3 study) and their 1-year open-label extensions were pooled to
      assess long-term effects of adjunctive topiramate on adaptive behavior in infants
      with clinical or video-electroencephalographic evidence of refractory, partial
      onset seizures. The primary safety and efficacy results of adjunctive topiramate
      treatment were reported previously. We report the changes in adaptive behavior of
      infants, based on Vineland Scales of Adaptive Behavior. Of 284 infants (mean
      [S.D.] age, 12 [6.3] months) enrolled, 89% (n = 252) manifested partial-onset
      seizures, and 41% (n = 116) manifested clinically relevant, symptomatic
      etiologies at pretreatment baseline. Overall, Vineland scores were below average
      at pretreatment baseline. The most frequently used concomitant antiepileptic
      drugs included valproic acid (59%), phenobarbital (31%), and carbamazepine (19%).
      The most common treatment-emergent cognitive and neuropsychiatric adverse events
      included anorexia (35%) and somnolence (27%). A clinically significant decline
      (approximately 15 points, or 1 S.D.) occurred in both Vineland Scales composite
      (mean change, -14.0) and domain standard scores from pretreatment baseline to
      open-label extension endpoint. However, individual domain raw scores increased,
      indicating that infants progressed in acquisitions of adaptive skill, but at a
      slower rate than the normative population.

PMID- 22633630
TI  - Effect of treatment of obstructive sleep apnea on seizure outcomes in children
      with epilepsy.
AB  - A retrospective review of children with epilepsy and obstructive sleep apnea,
      treated surgically for their obstructive sleep apnea from January 2008-October
      2010, was performed for age, sex, type of epilepsy, antiseizure medications,
      sleep-study data, and changes in seizure frequency. Twenty-seven subjects (median
      age, 5 years) with no adjustment to their medications around their time of
      surgery were identified. Three months after surgery, 10 (37%) patients became
      seizure-free, three (11%) demonstrated >50% seizure-reduction, and six (22%)
      exhibited an amelioration of seizure frequency. Two (7%) demonstrated unchanged
      seizure-frequency, and six (22%) manifested a worsening of seizure frequency.
      Median seizure frequency before surgery was 8.5 (interquartile range, 2-90), and
      after surgery, three (interquartile range, 0-75), with a 53% median seizure
      reduction. Multivariate analysis demonstrated a trend toward seizure freedom with
      each percentile increase in body mass index and early age of surgery. We conclude
      that obstructive sleep apnea surgery may decrease seizure frequency, especially
      in children with elevated body mass index scores and younger age at time of
      surgery.

PMID- 22633631
TI  - Microcephaly-thin corpus callosum syndrome maps to 8q23.2-q24.12.
AB  - Postnatal microcephaly is defined as normal head circumference at birth, which
      progressively declines to more than 2 standard deviations below the average for
      the patient's age and sex. We describe four patients from three consanguineous
      families of Arab Bedouin origin who presented with autosomal recessive
      inheritance of progressive microcephaly, spasticity, thin corpus callosum,
      pyramidal signs, and intellectual disability. Homozygosity mapping (Human Mapping
      NspI 250K arrays, Affymetrix, Santa Clara, CA) placed the disease locus at 8q23.2
      q24.12. The candidate region includes 22 known or predicted genes, including
      RAD21, which is related to the cohesion complex EIF3H, which is involved in
      translation initiation, and TAF2, which may be involved in intellectual
      disability. Identification of the causative gene in our reported family will shed
      light on the pathogenesis of this severe condition.

PMID- 22633632
TI  - Clinical features and neurologic progression of hyperargininemia.
AB  - Hyperargininemia is an autosomal recessive metabolic disorder caused by a
      deficiency of enzyme arginase I. It is a rare pan-ethnic disease with a clinical
      presentation distinct from that of other urea cycle disorders, and hyperammonemic
      encephalopathy is not usually observed. Hyperargininemia is one of the few
      treatable causes of pediatric spastic paraparesis, and can be confused with
      cerebral palsy. We retrospectively evaluated the clinical onset, neurologic
      manifestations, progression of abnormalities, electroencephalographic
      abnormalities, and laboratory findings of 16 Brazilian patients with
      hyperargininemia. Relevant data about the clinical spectrum and natural history
      of hyperargininemia are detailed. Progressive spastic diplegia constituted the
      key clinical abnormality in this group, but variability in clinical presentation
      and progression were evident in our series. Seizures in hyperargininemia may be
      more common than reported in previous studies. Features distinguishing
      hyperargininemia from cerebral palsy and hereditary spastic paraplegia are
      emphasized in this large series of patients.

PMID- 22633633
TI  - Immunoglobulin treatment for severe childhood epilepsy.
AB  - We have used intravenous immunoglobulin to treat pediatric patients with various
      severe epileptic conditions. This retrospective, multicenter study comprised 64
      consecutive patients treated with immunoglobulins for either epileptic
      encephalopathy or refractory epilepsy. The rate of full or partial improvement
      according to specific syndrome involved three of four patients with idiopathic
      West syndrome, six of 12 patients with electrical status epilepticus in sleep,
      eight of 19 patients with an undefined syndrome, one of three patients with
      Landau-Kleffner syndrome, and one of two patients with Rasmussen encephalitis.
      Intravenous immunoglobulins were ineffective in 10 patients with symptomatic West
      syndrome, nine with febrile infection-related status epilepticus, three with
      myoclonic astatic epilepsy, and two with Lennox-Gastaut syndrome. Nine patients
      (14%) demonstrated complete resolution, and 10 (15.6%) exhibited partial
      improvement. Of these 19 responders (29.7%), eight relapsed. Although intravenous
      immunoglobulin is not suitable for all cases of epilepsy, it may prove
      efficacious for specific epileptic syndromes, mainly idiopathic West syndrome and
      electrical status epilepticus during sleep.

PMID- 22633634
TI  - Management of patients with status epilepticus treated at a pediatric intensive
      care unit in Turkey.
AB  - We investigated the etiology, treatment, and prognosis of patients treated for
      status epilepticus at a pediatric intensive care unit. Medical records of 89
      patients admitted to a pediatric intensive care unit with status epilepticus were
      reviewed retrospectively. Patients ranged in age from 2 months to 18 years (mean
      age +/- S.D., 4.7 +/- 3.8 years). Seizure etiologies comprised remote symptomatic
      in 47 (52.7%), febrile in 15 (16.9%), acute symptomatic in 12 (13.5%), and
      unknown in 15 (16.9%). Seizure durations ranged from 30-60 minutes in 58
      patients, whereas 31 manifested refractory seizures longer than 60 minutes.
      Seizure control was achieved within 30 minutes in 55 patients, from 30-60 minutes
      in 19, and after 60 minutes in 15. Rectal diazepam was administered to 38 (42.7%)
      patients before admission to the hospital. Length of intensive care unit stay
      increased with increasing seizure duration (P < 0.05). The total mortality rate
      was 3.4%. This lower mortality rate may be considered evidence of the
      effectiveness and reliability of the status epilepticus treatment protocol in our
      pediatric intensive care unit. Prehospital rectal diazepam administration and the
      treatment of brain edema in the intensive care unit may be useful in the
      management of patients with status epilepticus.

PMID- 22633635
TI  - Favorable outcomes in acute necrotizing encephalopathy in a child treated with
      hypothermia.
AB  - Acute necrotizing encephalopathy predominately affects young children in Japan,
      Taiwan, and Korea. It manifests with fever, altered mental status, and seizures 2
      5 days after the onset of upper respiratory infection. It is commonly associated
      with influenzas A, B, and H1N1. The hallmark of the encephalopathy involves
      multifocal, symmetric brain lesions affecting the bilateral thalami, brainstem
      tegmentum, cerebral periventricular white matter, cerebellum, and medulla, as
      visualized by computed tomography and magnetic resonance imaging. Prognoses were
      uniformly dismal before 1980, with high mortality rates and severe neurologic
      sequelae in survivors. We describe a previously healthy 4-year-old Caucasian girl
      who presented with fever, alterations of consciousness, and convulsions. Nasal
      swab revealed her to be influenza A-positive, and her magnetic resonance imaging
      was diagnostic of the disease. Prompt recognition of the disease and treatment
      with hypothermia and anti-inflammatory agents led to a favorable outcome.

PMID- 22633636
TI  - Reversible visual evoked potential abnormalities in uremic children.
AB  - In this case study, two cystinosis-related uremic children were followed at the
      Department of Nephrology, University of Montreal Hospital Center Sainte-Justine.
      Pattern-reversal visual evoked potentials were recorded at two time points,
      during dialysis treatment (time 1) and after renal transplant (time 2). Data were
      compared with those obtained from a control group (n = 6). The P1 component was
      selected and analyzed as the electrophysiologic marker of interest. At time 1, P1
      latency was delayed, and P1 amplitude was reduced compared with control subjects.
      Both responses fell within normal range after kidney transplantation. These
      results indicate that renal failure and dialysis are associated with abnormal
      visual evoked potentials in children with chronic renal failure, but such
      alterations of visual processing are reversible after kidney transplant.

PMID- 22633637
TI  - Novel clinical features in pontine tegmental cap dysplasia.
AB  - Pontine tegmental cap dysplasia is a rare neurologic condition first described by
      Barth et al. in 2007. It is characterized by a vaulted pontine tegmentum
      projecting into the fourth ventricle and ventral pontine hypoplasia. Patients
      present with developmental delay, cerebellar and pyramidal abnormalities, cranial
      nerve dysfunction, and various extracranial malformations. The condition is
      thought to occur as a result of aberrant neuronal axonal guidance during
      embryologic development. Its genetic etiology has not been identified. We
      describe a further case of this rare condition with several features not
      previously reported, including aortic arch hypoplasia and mirror movements.

PMID- 22633638
TI  - A novel PCDH19 mutation inherited from an unaffected mother.
AB  - We report on a 13-year-old girl with a negative family history who manifested
      drug-resistant, mostly fever-induced seizures in clusters from age 5 months.
      Seizure frequency was not substantially reduced by anticonvulsant treatment, but
      tended to decrease with age. Early behavioral changes, i.e., autistic and
      aggressive features, worsened with time. Molecular genetic testing for PCDH19
      mutations was performed by sequencing all exons of the gene, and revealed
      duplication c.2705dupA (p.Asp902Lysfs*6) in exon 5, which was also present in the
      fully asymptomatic mother. This case is among the few reported with a pathogenic
      PCDH19 mutation inherited from an unaffected heterozygous female carrier. It
      indicates that PCDH19 mutation testing should be performed in sporadic cases with
      no family history that still demonstrate well-established features of peculiar X
      linked epilepsy with mental retardation limited to females.

PMID- 22633639
TI  - Two novel missense mutations observed in nonketotic hyperglycinemia.
AB  - Nonketotic hyperglycinemia, also known as glycine encephalopathy, is an autosomal
      recessive disorder of an inborn error of the glycine metabolism, caused by
      deficiency in the mitochondrial glycine cleavage enzyme. The majority of cases
      are caused by mutations in P-protein, one of the four components of the glycine
      cleavage enzyme, glycine decarboxylase. We describe a male neonate with
      hypotonia, hiccups, and persistent apnea, but without seizures. The patient's
      glycine level in cerebrospinal fluid and plasma was 328.3 nmol/mL (reference
      value, 2.2-14.2 nmol/mL) and 1439 nmol/mL (reference value, 232-740 nmol/mL),
      respectively. The cerebrospinal fluid/plasma ratio of 0.228 represented an
      increase (normal range, <0.04). Two novel heterozygous missense mutations
      (c.1130C>T (p.A377V) and c.2081_2088del (p.A694DfsX11) in exons 8 and 18) in the
      glycine decarboxylase gene confirmed the diagnosis of nonketotic hyperglycinemia.

PMID- 22633640
TI  - Dyskinesias as a limiting factor in the treatment of Segawa disease.
AB  - Patients with autosomal dominant Segawa disease (dopa-responsive dystonia)
      demonstrate excellent, sustained response to low-dose levodopa. In contrast, the
      development of levodopa limiting treatment dyskinesias is thought to support the
      diagnosis of other early-onset dystonia/parkinsonism syndromes. We describe an
      atypical phenotype of persistent treatment limiting dyskinesias in a family with
      prominent brachial dystonia and a novel GCH1 mutation. The pedigree comprised two
      affected members: the proband (aged 13 years) and her mildly affected mother
      (aged 48 years). A phenylalanine loading test, cerebrospinal fluid for biogenic
      amines and pterins, guanosine triphosphate cyclohydrolase I enzyme activity, and
      direct exonic sequencing of GCH1 revealed a novel mutation (c.235_240delCTGAGC
      [p.L79_S80del]) in the GCH1 gene. Despite continuous levodopa therapy from age 7
      years, the proband developed severe writer's cramp at age 10 years and persistent
      treatment limiting dyskinesias, with even low doses of levodopa leading to
      treatment challenges. Dyskinesias as limiting side effects of levodopa should not
      preclude a diagnosis of dopa-responsive dystonia during diagnostic levodopa
      trials. A diagnosis of Segawa disease should still be considered if partial
      improvement occurs with levodopa, but with dose-limiting dyskinesias.

PMID- 22633641
TI  - Brown-Vialetto-Van Laere syndrome: a riboflavin-unresponsive patient with a novel
      mutation in the C20orf54 gene.
AB  - Brown-Vialetto-Van Laere syndrome (Online Mendelian Inheritance in Man number
      211530) is a neurodegenerative disorder characterized by pontobulbar palsy
      affecting cranial nerves (mainly VII-XII). Sensorineural deafness is often the
      leading sign, followed by other neurologic signs. Inheritance is often autosomal
      recessive, with mutations in the C20orf54 gene (Online Mendelian Inheritance in
      Man number 613350). Three previous patients with mutations in the C20orf54 gene
      and clinical signs of Brown-Vialetto-Van Laere or Fazio-Londe syndrome revealed a
      metabolic profile suggesting a multiple acyl-coenzyme A dehydrogenase defect.
      They benefited from riboflavin. We describe a 3-year-old girl with early-onset
      Brown-Vialetto-Van Laere syndrome and a novel mutation in the C20orf54 gene
      (c.989G>T). On T(2)-weighted imaging, increased signal intensity of the
      vestibular nuclei bilaterally, the pedunculus cerebellaris superior and the
      central tegmental tract were observed during acute clinical deterioration. Her
      metabolic profile was normal. Trials with steroids, immunoglobulins, and
      riboflavin produced no effect. The patient recovered slowly during subsequent
      months, with residual deficits. Brown-Vialetto-Van Laere syndrome should be
      considered in patients with sensorineural hearing loss and pontobulbar palsy.
      Patients should be screened for riboflavin deficiency and a therapy with
      riboflavin may provide effective treatment in some affected patients.

PMID- 22633643
TI  - Topiramate use in the neonatal period.

PMID- 22633644
TI  - A case of chronic pancreatitis with celiac axis stenosis complicated by hepatic
      artery pseudoaneurysm: a therapeutic challenge.
AB  - BACKGROUND: While hepatic artery pseudoaneurysm is an uncommon complication of
      the chronic pancreatitis, celiac axis stenosis has rarely been reported in
      chronic pancreatitis. Although both of these entities have been reported in
      isolation, simultaneous occurrence of these two problems in one patient of
      chronic pancreatitis has not been reported so far. METHODS: A 32-year-old
      nonalcoholic male presented with hematemesis and melena for one month. He had
      undergone longitudinal pancreatico-jejunostomy for the idiopathic chronic
      pancreatitis one year back. Esophagogastroduodenoscopy could not find any source,
      but CT angiography revealed a 1.5 * 1.5 cm common hepatic artery pseudoaneurysm
      along with the complete stenosis of the celiac axis. RESULTS: As the endovascular
      approach was not found to be feasible, surgical ligation of the pseudoaneurysm
      was performed. Intraoperatively, peripancreatic adhesions with multiple arterial
      collaterals were found. Patient had an uneventful postoperative recovery, and has
      been well during the last six months of follow up with no recurrence of bleeding.
      CONCLUSIONS: As the presence of celiac axis stenosis may alter the management
      plan of bleeding visceral artery pseudoaneurysm, this abnormality should always
      be looked for in CT angiography performed for suspected bleeding visceral artery
      pseudoaneurysm.

PMID- 22633645
TI  - Nesidioblastosis in a simmental calf.
AB  - A 2-day-old Simmental calf with arthrogryposis and astasia was subjected to
      necropsy examination. The calf was normoglycaemic and normoinsulinaemic.
      Microscopically, pancreatic tissue was hyperplastic with an irregular lobular
      arrangement of pancreatic islets. Newly-formed islet cells budded from
      intralobular or intercalated ducts (so-called ductulo-insular complexes) and
      there were prominent blood vessels with telangiectatic features surrounded by
      rows of cuboidal-columnar islet cells. The newly-formed islets expressed insulin
      antigen immunohistochemically. The lesion was diagnosed as nesidioblastosis, an
      uncommon abnormality previously associated with the double muscling trait in
      cattle.

PMID- 22633646
TI  - Immunohistochemical expression of COX-2, mPGES and EP2 receptor in normal and
      reactive canine bone and in canine osteosarcoma.
AB  - Accumulating evidence suggests that cyclooxygenase (COX)-2 is involved in the
      pathogenesis of human and canine osteosarcoma. The aim of this study was to
      investigate the expression of COX-2 in normal, reactive and neoplastic canine
      bone and the events downstream to COX-2 that lead to prostaglandin E(2) (PGE(2))
      production. COX-2, microsomal PGE(2) synthase-1 (mPGES-1) and the PGE(2) receptor
      (EP2) were assessed by immunohistochemistry in 12 samples of normal bone, 14
      cases of fracture callus and 27 appendicular osteosarcomas. No immunoreactivity
      to COX-2, mPGES-1 or EP2 receptor was observed in normal bone. Fifty percent of
      reactive bone samples expressed COX-2 and 57% expressed mPGES-1 and EP2 receptor,
      although with weak labelling intensity. Ninety-three percent of osteosarcomas
      expressed COX-2, while mPGES-1 was expressed by 85% and EP2 receptor by 89% of
      the tumours. The data confirm that COX-2 is expressed at high level in
      osteosarcoma and support the use of COX-2 inhibitors to improve the response to
      chemotherapy. The possibility of blocking the EP2 or the selective inhibition of
      mPGES-1, rather than COX-2 activity, might decrease the incidence of adverse
      effects that occur due to the inhibition of prostanoids other than PGE(2).

PMID- 22633648
TI  - Adversities of being infertile: the experience of Jordanian women.
AB  - OBJECTIVE: To describe and interpret the experiences of and adversities faced by
      infertile Jordanian women as described from their own perspectives. DESIGN: A
      qualitative descriptive design. SETTING: The women were interviewed at a
      nonprofit women's organization in the north of Jordan. The organization focuses
      on empowerment and health issues. PATIENT(S): This study included a purposive
      sample of 25 infertile Jordanian women who were unsuccessfully trying to conceive
      for a minimum of 1 year, and who were receiving treatment for infertility.
      INTERVENTION(S): Face-to-face, in-depth, semistructured interviews were
      conducted, audiotaped, and transcribed using thematic analysis. MAIN OUTCOME
      MEASURE(S): Outcomes were measured using thematic analysis of the interview
      transcripts. RESULT(S): Four key adversity themes emerged from the data: the
      adversity of incomplete being, the social adversity of being infertile, the
      adversity of another wife, and the adversity of changes in the marital
      relationship. CONCLUSION(S): Jordanian women are seriously affected by
      infertility and experience personal, social, and marital adversities, which
      affect their well-being. These adversities need to be conceptualized within a
      framework that can be used to empower and counsel infertile women in all aspects
      of life.

PMID- 22633649
TI  - Recombinant LH supplementation in women of 35 years and older undergoing IVF?

PMID- 22633651
TI  - In vitro fertilization and breast cancer: is there cause for concern?
AB  - OBJECTIVE: To examine the incidence rate of breast cancer in a cohort of women
      undergoing treatment for infertility, comparing the rate in women who had in
      vitro fertilization (IVF) with those who did not. DESIGN: Population-based cohort
      study using linked hospital and registry data. SETTING: Hospital. PATIENT(S): All
      women aged 20-44 years seeking hospital investigation and treatment for
      infertility in Western Australia during the period 1983-2002 (n = 21,025).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Hazard ratios (HRs) for breast
      cancer. RESULT(S): There was no overall increase in the rate of breast cancer in
      women who had IVF (HR 1.10, 95% confidence interval [CI] 0.88-1.36), but there
      was an increased rate in women who commenced IVF at a young age. Women who
      commenced hospital infertility treatment at 24 years and required IVF had an
      unadjusted HR of breast cancer of 1.59 (95% CI 1.05-2.42) compared with women of
      the same age who had infertility treatment but no IVF. When adjusted for late age
      at first delivery, which is associated with an increased rate of breast cancer,
      and delivery of twins and higher-order multiples, which is associated with a
      decreased rate of breast cancer, the HR remained elevated at 1.56 (95% CI 1.01
      2.40). Hazard ratios were not elevated in women who commenced treatment at age 40
      and required IVF (adjusted HR 0.87, 95% CI 0.62-1.22). CONCLUSION(S): Commencing
      IVF treatment at a young age is associated with an increased rate of breast
      cancer.

PMID- 22633650
TI  - Adiponectin and its receptors modulate granulosa cell and cumulus cell functions,
      fertility, and early embryo development in the mouse and human.
AB  - OBJECTIVE: To study the expression and function of adiponectin and its receptors
      in mouse and human follicle cells and in early embryo development. DESIGN: Whole
      ovaries, granulosa cells, and cumulus-oocyte complexes isolated from immature
      mice before and during hormone-induced ovulation were used to analyze the
      expression of adiponectin, its receptors, and ovulation-related genes; human
      cumulus cells and granulosa cells were isolated from patients undergoing in vitro
      fertilization (IVF) procedures. SETTING: Multicenter. PATIENT(S): Women in IVF
      programs in Japan and the United States. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Expression of adiponectin receptors and fertility. RESULT(S):
      Adiponectin expression is absent/low in mouse and human granulosa cells and
      cumulus cells. Adiponectin receptors are hormonally regulated in mouse granulosa
      and cumulus cells in vivo and in culture. Adiponectin differentially alters the
      expression of Adipor1/Adipor2 as well as genes related to steroidogenesis,
      ovulation, and apoptosis in cumulus cells versus granulosa cells. Adiponectin
      enhances oocyte maturation and early embryo development in mouse and human IVF
      procedures. CONCLUSION(S): Adiponectin can modulate not only follicle growth but
      also embryo development in mice and humans.

PMID- 22633652
TI  - Extra-aortic identifiers to guide genetic testing in familial thoracic aortic
      aneurysms and dissections syndromes: it is all about the company one keeps.

PMID- 22633653
TI  - Mortality benefit with prasugrel in the TRITON-TIMI 38 coronary artery bypass
      grafting cohort: risk-adjusted retrospective data analysis.
AB  - OBJECTIVES: The objective of this study was to characterize the bleeding,
      transfusion, and other outcomes of patients related to the timing of prasugrel or
      clopidogrel withdrawal before coronary artery bypass grafting (CABG). BACKGROUND:
      There is little evidence to guide clinical decision making regarding the use of
      prasugrel in patients who may need urgent or emergency CABG. Experience with
      performing CABG in the presence of clopidogrel has raised concern about
      perioperative bleeding complications that are unresolved. METHODS: A subset of
      the TRITON-TIMI 38 study (Trial to Assess Improvement in Therapeutic Outcomes by
      Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial
      Infarction 38), in which patients with acute coronary syndrome were randomized to
      treatment with aspirin and either clopidogrel or prasugrel, underwent isolated
      CABG (N = 346). A supplemental case report form was designed and administered,
      and the data combined with the existing TRITON-TIMI 38 database. Baseline
      imbalances were corrected for using elements of the European System for Cardiac
      Operative Risk Evaluation and The Society of Thoracic Surgeons predictive
      algorithm. RESULTS: A significantly higher mean 12-h chest tube blood loss (655
      +/- 580 ml vs. 503 +/- 378 ml; p = 0.050) was observed with prasugrel compared
      with clopidogrel, without significant differences in red blood cell transfusion
      (2.1 U vs. 1.7 U; p = 0.442) or the total donor exposure (4.4 U vs. 3.0 U; p =
      0.463). All-cause mortality was significantly reduced with prasugrel (2.31%)
      compared with 8.67% with clopidogrel (adjusted odds ratio: 0.26; p = 0.025).
      CONCLUSIONS: Despite an increase in observed bleeding, platelet transfusion, and
      surgical re-exploration for bleeding, prasugrel was associated with a lower rate
      of death after CABG compared with clopidogrel.

PMID- 22633654
TI  - Virtual electrophysiological study in a 3-dimensional cardiac magnetic resonance
      imaging model of porcine myocardial infarction.
AB  - OBJECTIVES: This study sought to test the hypothesis that "virtual"
      electrophysiological studies (EPS) on an anatomic platform generated by 3
      dimensional magnetic resonance imaging reconstruction of the left ventricle can
      reproduce the reentrant circuits of induced ventricular tachycardia (VT) in a
      porcine model of myocardial infarction. BACKGROUND: Delayed-enhancement magnetic
      resonance imaging has been used to characterize myocardial infarction and "gray
      zones," which are thought to reflect heterogeneous regions of viable and
      nonviable myocytes. METHODS: Myocardial infarction by coronary artery occlusion
      was induced in 8 pigs. After a recovery period, 3-dimensional cardiac magnetic
      resonance images were obtained from each pig in vivo. Normal areas, gray zones,
      and infarct cores were classified based on voxel intensity. In the computer
      model, gray zones were assigned slower conduction and longer action potential
      durations than those for normal myocardium. Virtual EPS was performed and
      compared with results of actual in vivo programmed stimulation and noncontact
      mapping. RESULTS: The left ventricular volumes ranged from 97.8 to 166.2 cm(3),
      with 4.9% to 17.5% of voxels classified as infarct zones. Six of the 7 pigs in
      which VT developed during actual EPS were also inducible with virtual EPS. Four
      of the 6 pigs that had simulated VT had reentrant circuits that approximated the
      circuits seen with noncontact mapping, whereas the remaining 2 had similar
      circuits but propagating in opposite directions. CONCLUSIONS: This initial study
      demonstrates the feasibility of applying a mathematical model to magnetic
      resonance imaging reconstructions of the left ventricle to predict VT circuits.
      Virtual EPS may be helpful to plan catheter ablation strategies or to identify
      patients who are at risk of future episodes of VT.

PMID- 22633655
TI  - Aggressive cardiovascular phenotype of aneurysms-osteoarthritis syndrome caused
      by pathogenic SMAD3 variants.
AB  - OBJECTIVES: The purpose of this study was describe the cardiovascular phenotype
      of the aneurysms-osteoarthritis syndrome (AOS) and to provide clinical
      recommendations. BACKGROUND: AOS, caused by pathogenic SMAD3 variants, is a
      recently described autosomal dominant syndrome characterized by aneurysms and
      arterial tortuosity in combination with osteoarthritis. METHODS: AOS patients in
      participating centers underwent extensive cardiovascular evaluation, including
      imaging, arterial stiffness measurements, and biochemical studies. RESULTS: We
      included 44 AOS patients from 7 families with pathogenic SMAD3 variants (mean
      age: 42 +/- 17 years). In 71%, an aortic root aneurysm was found. In 33%,
      aneurysms in other arteries in the thorax and abdomen were diagnosed, and in 48%,
      arterial tortuosity was diagnosed. In 16 patients, cerebrovascular imaging was
      performed, and cerebrovascular abnormalities were detected in 56% of them.
      Fifteen deaths occurred at a mean age of 54 +/- 15 years. The main cause of death
      was aortic dissection (9 of 15; 60%), which occurred at mildly increased aortic
      diameters (range: 40 to 63 mm). Furthermore, cardiac abnormalities were
      diagnosed, such as congenital heart defects (6%), mitral valve abnormalities
      (51%), left ventricular hypertrophy (19%), and atrial fibrillation (22%). N
      terminal brain natriuretic peptide (NT-proBNP) was significantly higher in AOS
      patients compared with matched controls (p < 0.001). Aortic pulse wave velocity
      was high-normal (9.2 +/- 2.2 m/s), indicating increased aortic stiffness, which
      strongly correlated with NT-proBNP (r = 0.731, p = 0.005). CONCLUSIONS: AOS
      predisposes patients to aggressive and widespread cardiovascular disease and is
      associated with high mortality. Dissections can occur at relatively mildly
      increased aortic diameters; therefore, early elective repair of the ascending
      aorta should be considered. Moreover, cerebrovascular abnormalities were
      encountered in most patients.

PMID- 22633656
TI  - Simulation model of cardiac three dimensional accelerometer measurements.
AB  - A miniaturized accelerometer sensor attached to the heart may be applied for
      monitoring cardiac motion. Proper understanding of the sensor measurements is
      required for successful development of algorithms to process the signal and
      extract clinical information. In vivo testing of such sensors is limited by the
      invasive nature of the procedure. In this study we have developed a mathematical
      simulation model of an accelerometer attached to the heart so that testing
      initially may be performed on realistic, simulated measurements. Previously
      recorded cardiac motion by sonomicrometric crystals was used as input to the
      model. The three dimensional motion of a crystal attached to the heart served as
      the simulated motion of the accelerometer, providing the translational
      acceleration components. A component of gravity is also measured by the
      accelerometer and fused with the translational acceleration. The component of
      gravity along an accelerometer axis varies when the axis direction slightly
      rotates as the accelerometer moves during the cardiac cycle. This time-varying
      gravity component has substantial effects on the accelerometer measurements and
      was included in the simulation model by converting the motion to prolate
      spheroidal coordinates where the axis rotation could be found. The simulated
      accelerometer signal was filtered and integrated to velocity and displacement.
      The resulting simulated motion was consistent with previous accelerometer
      recordings during normal and ischemic conditions as well as for alterations of
      accelerometer orientation and patient positions. This suggests that the model
      could potentially be useful in future testing of algorithms to filter and process
      accelerometer measurements.

PMID- 22633657
TI  - [Position statement of the Catalan Society of Digestology on sedation in
      gastrointestinal endoscopy].

PMID- 22633658
TI  - [The ups and downs of the impact factor: every cloud has a silver lining].

PMID- 22633659
TI  - [Functional impairment and its impact on sporting activities after latissimus
      dorsi flap breast reconstruction].
AB  - AIM OF THE STUDY: The latissimus dorsi flap is commonly used for breast
      reconstruction. Donor site morbidity is the major side effect of this surgery.
      However, if the impact of the latissimus dorsi muscle removal on daily living
      activities has already been studied, few data are available about its
      consequences on sporting activities. MATERIAL AND METHOD: Our retrospective
      monocentric study reviewed 75 consecutive female patients who underwent
      latissimus dorsi muscle transfer for breast reconstruction with a mean follow-up
      of 32.4 months. Patients had to answer a questionnaire per phone about their
      sporting, daily living and working activities before and after surgery. If they
      felt any changes after surgery, the type of limitation was detailed (pain,
      strength, endurance). RESULTS: We showed a reduction in sporting activities for
      43% patients practising a sport using the upper limb compared to 19% for them
      using the lower limb (P<0.05%). Eighty-three percent of the patients felt
      restricted for at less one activity of daily living. 5.2% had to adapt their
      working conditions after surgery. CONCLUSION: The reduction in sporting
      activities using the upper limb after surgery suggests a negative impact of the
      surgery. However, other factors than the latissimus dorsi muscle removal might
      contribute to this reduction.

PMID- 22633660
TI  - [Jacques Mathieu Delpech and School of Montpellier: 1st part Jacques Mathieu
      Delpech (1777-1832)].
AB  - Two surgeons have labeled, in France, the first period of the 19th century. The
      one is universally known, it is Dupuytren, the other one underestimated who can
      be nevertheless considered as his equal: Jacques Mathieu Delpech. From Toulouse,
      child of the Revolution, he taught the anatomy from the age of 14 years, became
      assistant chief warrant officer in the revolutionary armies, gave up competing
      with Dupuytren, and became Professor of Surgery in Montpellier in 1812. Delpech
      reintroduced the teaching of the Anatomy and the Surgery. Author of first
      forehead flap in France, he revolutionized the treatment of the clubfoot. He
      created an Institute of Orthomorphia where he made practice the gymnastics and
      the active reeducation. He was interested in the healing process and in the
      correction of the deformations of the body. He was murdered when he was 55 by one
      of his patients. He is the founder of the School of plastic surgery of
      Montpellier, which will compete in the 19th century with the school of Berlin of
      Dieffenbach.

PMID- 22633661
TI  - Association between Lipoprotein (a) level on admission and the incidence of
      subsequent cardiovascular events in patients with acute coronary syndrome.

PMID- 22633662
TI  - Admission B-type natriuretic peptide retains prognostic value in patients with
      acute coronary syndrome and preserved left ventricular ejection fraction.

PMID- 22633663
TI  - Distal protection device aggravated microvascular obstruction evaluated by
      cardiac MR after primary percutaneous intervention for ST-elevation myocardial
      infarction.
AB  - BACKGROUND: Protection of distal embolization by balloon occlusion and thrombus
      aspiration has not improved microvascular circulation nor decreased myocardial
      injury during primary percutaneous intervention (PCI) for ST-elevation myocardial
      infarction (STEMI) in randomized trials. In a prospective randomized trial, we
      investigated the mechanism of the poor effect of distal protection and thrombus
      aspiration (DP-TA) in 126 patients with STEMI. METHODS: Patients with first
      diagnosed STEMI were randomly assigned to DP-TA pretreatment or conventional PCI
      (c-PCI). Primary endpoint was reduced left ventricular end-diastolic volume
      (LVEDV) measured by MRI at post-PCI and 6 months after PCI. Secondary end points
      were infarct ratio (infarct size to entire LV size) by delayed enhancement (DE),
      area at risk (AAR) ratio (AAR to entire LV size) by T2 high signal, microvascular
      occlusion index (MVO) ratio (MVO to entire LV size) by DE, and myocardial salvage
      index (MSI: (AAR--infarct size)*100/AAR) using cardiac magnetic resonance imaging
      (MRI) within 3 days after PCI. RESULTS: Baseline characteristics of the patients
      including cardiovascular risk factors and lesion characteristics were similar
      between the two groups. DT-PA failed to improve LV remodeling at 6 months (LVEDV
      140 +/- 39 vs 133 +/- 37 in c-PCI group, p=0.418). Infarct ratio, AAR ratio and
      MSI were not statistically different between DP-TA group and c-PCI group.
      However, MVO ratio was significantly larger in DP-TA group than in c-PCI group
      (2.4 +/- 2.7 vs 1.1 +/- 1.9, p=0.045). CONCLUSION: DP-TA was potentially
      hazardous in primary PCI for STEMI by increasing MVO. DP-TA should not be used in
      STEMI.

PMID- 22633664
TI  - Surgical treatment of functional mitral regurgitation.
AB  - Incidence of functional mitral regurgitation (FMR) is increasing due to aging and
      better survival after acute myocardial infarction, the most frequent cause of
      FMR. At the basis of FMR there is a displacement of one of both papillary
      muscle(s) and/or annular enlargement, which can be primitive or, more often,
      secondary. There is general agreement that its natural history is unfavorable, as
      witnessed by a considerable body of evidences. However, even if there is no clear
      evidence that surgical treatment of FMR changes consistently the outcome of
      patients with this disease, at least in terms of survival, there are some studies
      which show that function improves, as well as the global quality of life. The
      guidelines reflect this uncertainty, providing no clear indications, even in the
      gradation of severity of the FMR. Surgical techniques are variable and are mainly
      addressed to the annulus (restrictive annuloplasty), which is only a part of the
      anatomic problem related to FMR. Insertion of a prosthesis inside the native
      valve is appearing more and more a valuable option rather than a bail out
      procedure. On the other side, techniques addressed to modify the position of the
      papillary muscles appear to be still under investigation and not yet in the
      armamentarium of surgical treatment of FMR. Even after many years, rules are not
      established and results are fluctuating, but how and when to treat FMR is
      becoming more and more a topic of interest in cardiac surgery.

PMID- 22633665
TI  - Right atrial substrate remodeling and atrioventricular node conduction properties
      in patients with paroxysmal atrial fibrillation.

PMID- 22633666
TI  - A novel 5' splice site mutation of SCN5A associated with Brugada syndrome
      resulting in multiple cryptic transcripts.

PMID- 22633668
TI  - Heart failure epicardial fat increases atrial arrhythmogenesis.
AB  - BACKGROUND: Obesity is an important risk factor for atrial fibrillation (AF) and
      heart failure (HF). The effects of epicardial fat on atrial electrophysiology
      were not clear. This study was to evaluate whether HF may modulate the effects of
      epicardial fat on atrial electrophysiology. METHODS: Conventional microelectrodes
      recording was used to record the action potential in left (LA) and right (RA)
      atria of healthy (control) rabbits before and after application of epicardial fat
      from control or HF (ventricular pacing of 360-400 bpm for 4 weeks) rabbits.
      Adipokine profiles were checked in epicardial fat of control and HF rabbits.
      RESULTS: The LA 90% of AP duration was prolonged by control epicardial fat (from
      77 +/- 6 to 87 +/- 7 ms, p<0.05, n=7), and by HF epicardial fat (from 78 +/- 3 to
      98 +/- 4 ms, p<0.001, n=9). However, control or HF epicardial fat did not change
      the AP morphology in RA. HF epicardial fat increased the contractility in LA (61
      +/- 11 vs. 35 +/- 6 mg, p=0.001), but not in RA. Control fat did not change the
      LA or RA contractility. Moreover, control and HF epicardial fat induced early and
      delayed afterdepolarizations in LA and RA, but only HF epicardial fat provoked
      spontaneous activity and burst firing in LA (n=3/9, 33.3% vs. n=0/7, 0%, n=0/9,
      0%, p<0.05). Compared to control fat, HF epicardial fat, had lower resistin, C
      reactive protein and serum amyloid A, but similar interleukin-6, leptin, monocyte
      chemotactic protein-1, adiponectin and adipsin. CONCLUSIONS: HF epicardial fat
      increases atrial arrhythmogenesis, which may contribute to the higher atrial
      arrhythmia in obesity.

PMID- 22633667
TI  - Transcatheter aortic valve implantation versus surgical aortic valve replacement
      for severe aortic stenosis: results from an intermediate risk propensity-matched
      population of the Italian OBSERVANT study.
AB  - BACKGROUND: Few studies have yielded information on comparative effectiveness of
      transcatheter aortic valve implantation (TAVI) versus surgical aortic valve
      replacement (SAVR) procedures in a real-world setting. The aim of this analysis
      is to describe procedural and post-procedural outcomes in a TAVI/SAVR
      intermediate risk propensity-matched population. METHODS: OBSERVANT is an
      observational prospective multicenter cohort study, enrolling AS patients
      undergoing SAVR or TAVI. Propensity score method was applied to analyze
      procedural and post-procedural outcomes. Pairs of patients with the same
      probability score were matched (caliper matching). RESULTS: The unadjusted
      enrolled population (N=2108) comprises 1383 SAVR patients, 602 transarterial-TAVI
      patients and 123 transapical-TAVI patients. Matched population comprised a total
      of 266 patients (133 patients for each group). A relatively low risk population
      was selected (mean logistic EuroSCORE 9.4 +/- 10.4% vs 8.9 +/- 9.5%, SAVR vs
      TAVI; p=0.650). Thirty-day mortality was 3.8% for both SAVR and TAVI (p=1.000).
      The incidence of stroke (1.5% SAVR and 0.0% TAVI; p=0.156) and myocardial
      infarction (0.8% SAVR and 0.8% TAVI; p=1.000) was not statistically different
      between groups, whereas a higher requirement for blood transfusion was reported
      across the surgical cohort (49.6% vs 36.1%; p=0.026). A higher incidence of major
      vascular damage (5.3% vs. 0.0%; p=0.007) and pacemaker implantation(0.8% vs
      12.0%; p=0.001) were reported in the TAVI group. CONCLUSIONS: Patients undergoing
      transcatheter and surgical treatment of severe aortic stenosis are still
      extremely distinct populations. In the relatively low-risk propensity-matched
      population analyzed, despite similar procedural and 30-day mortality, SAVR was
      associated with a higher risk for blood transfusion, whereas TAVI showed a
      significantly increased rate of vascular damage, permanent AV block and residual
      aortic valve regurgitation.

PMID- 22633669
TI  - Headache response to nitrate in patients with coronary artery disease and
      systolic heart failure.

PMID- 22633670
TI  - Elevation of serum cardiac troponin I in a cross-sectional cohort of asymptomatic
      subjects with Friedreich ataxia.
AB  - BACKGROUND: Friedreich ataxia is an autosomal recessive neurodegenerative
      disorder characterized by ataxia of all four limbs, dysarthria, areflexia, and
      cardiomyopathy. At present, baseline values of cardiac troponin I are unknown
      among Friedreich ataxia subjects. METHODS: In this study, we evaluated baseline
      plasma cardiac troponin I levels among a cross-sectional cohort of 49 pediatric
      and adult Friedreich ataxia subjects without active arrhythmia, chest pain or
      features of acute coronary syndrome at the time of sampling. We also reviewed
      baseline electrocardiograms from 45 of these subjects. RESULTS: Troponin I values
      were elevated above the 99th percentile population cutoff in 46.9% of all
      subjects, with 16.3% of asymptomatic subjects having levels typically seen during
      an acute myocardial infarction. In logistic regression models, younger age and an
      earlier disease onset predicted higher serum cardiac troponin I values. Only weak
      correlations were seen between cardiac troponin I values and echocardiogram
      parameters, including ejection fraction. Additionally, 82.2% of subjects also had
      abnormal baseline electrocardiograms. CONCLUSION: The present study demonstrates
      that both abnormal electrocardiograms and elevated serum cardiac troponin I
      values may be common baseline characteristics seen in Friedreich ataxia subjects.
      Further longitudinal studies will allow for a better understanding of the cause
      and prognostic implications of elevated levels, as well as the clinical utility
      of serum cardiac troponin I testing in Friedreich ataxia.

PMID- 22633671
TI  - Effects of atorvastatin and rosuvastatin on renal function: a meta-analysis.
AB  - BACKGROUND: Atorvastatin (A) and rosuvastatin (R) are highly effective and widely
      used statins. However, conflicting results have been reported regarding their
      renal effects. The aim of the present study was to compare the effects of A and R
      on glomerular filtration rate (GFR) and new onset proteinuria in patients at high
      cardiovascular risk. METHODS: Randomized trials about A or R treatments reporting
      clinical end-points were included in the meta-analysis. Influence of both
      treatments on GFR and new onset proteinuria was assessed. RESULTS: 23 trials
      enrolling 29,147 participants were included. A significant reduction in GFR was
      detected in placebo-treated compared to statin-treated patients (standard mean
      difference [SMD]: 0.056, 95% confidence interval [CI]:0.028 to 0.083, p<0.01). In
      particular, a significant reduction in GFR was detected in placebo as compared to
      either R-treated (SMD: 0.052, CI: 0.022 to 0.081, p=0.001) or A-treated patients
      (SMD: 0.084, CI: 0.008 to 0.161, p=0.031). No significant difference in GFR was
      detected in 5 head-to-head studies comparing A to R (SMD: 0.043, CI: -0.041 to
      0.126, p=0.319). In 9 studies comparing A to R, R treatment significantly
      increased the risk of proteinuria when compared to A (odds ratio [OR]: 0.656, CI:
      0.440 to 0.977, p=0.038, heterogeneity p=0.026), but this effect was no longer
      significant when studies using highest therapeutic doses of R (40 mg/daily) were
      excluded from analysis, abolishing significant heterogeneity (OR: 1.505, CI:
      0.827 to 2.739, p=0.181). CONCLUSIONS: A and R show similar reno-protective
      effects in patients at high cardiovascular risk, with comparable rates of new
      onset proteinuria when commonly used doses are considered.

PMID- 22633672
TI  - Should computed tomography coronary angiography be aborted when the calcium score
      exceeds a certain threshold in patients with chest pain?
AB  - BACKGROUND: There is ongoing debate about whether a computed tomography coronary
      angiography (CTCA) should be aborted when the calcium score (CS) exceeds a
      certain threshold in patients with chest pain. The aim of this study was to
      discover whether specific "cutpoints" regarding coronary artery CS could be
      determined to predict severe coronary stenoses assessed by CTCA, thus identifying
      patients amenable to an invasive diagnostic approach. METHODS: 294 consecutive
      patients with chest pain of uncertain cause who were referred for non-invasive
      diagnostic CTCA were included. Subjects underwent Agatston CS and CTCA using
      current 64-slice technology. RESULTS: Severe coronary stenoses were noted in 75
      of 294 (25.1%) patients on CTCA. A very high prevalence of severe coronary
      stenoses was found in patients with CS >= 400 (87.0%). The CS had area under the
      ROC curve 0.86 to predict severe coronary stenoses on CTCA. The best discriminant
      cut-off point was CS >= 400 (sensitivity of 55.3%, specificity of 93.5, positive
      predictive value of 85.8%, negative predictive value of 84.0%). Multivariable
      logistic regression analysis controlling for traditional risk factors showed CS
      >= 400 remained an independent predictor of severe coronary stenoses on CTCA (OR
      14.553, 95% confidence interval 4.043 to 52.384, p<0.001). CONCLUSIONS: CS can be
      used as a "gatekeeper" to CTCA in patients with chest pain. Due to the very high
      prevalence of severe coronary stenoses in patients with CS >= 400, further
      evaluation with CTCA is not warranted as these patients should be referred to
      invasive coronary angiography, avoiding the repeated exposure to ionizing
      radiation and iodinated contrast.

PMID- 22633673
TI  - Antagonists of organic anion transporters 1 and 3 ameliorate adverse cardiac
      remodelling induced by uremic toxin indoxyl sulfate.

PMID- 22633674
TI  - High risk sudden death patients with anomalous coronary arteries presented
      clinically with chest discomfort diagnosed by multi-detector computed tomographic
      angiography.

PMID- 22633675
TI  - Decreased serum endogenous secretory receptor for advanced glycation endproducts
      and increased cleaved receptor for advanced glycation endproducts levels in
      patients with atrial fibrillation.

PMID- 22633676
TI  - Typical and atypical Takotsubo syndrome in the same patient.

PMID- 22633677
TI  - Management and timing of access-site vascular complications occurring after trans
      radial percutaneous coronary procedures.
AB  - BACKGROUND: Access-site vascular complications (ASVC) in patients undergoing
      trans-radial coronary procedures are rare but may have relevant clinical
      consequences. Data regarding the optimal management of radial-access-related ASVC
      are lacking. METHODS: During a period of 6 years we prospectively collected ASVC.
      ASVC were defined as any complication requiring ultrasound examination or upper
      limb angiography. ASVC were categorized according to the timing of diagnosis:
      "very early" (in the cath lab), "early" (after cath lab discharge, but during the
      hospital stay) and "late" (after hospital discharge). The need of surgery
      (primary end-point) and the development of neurological hand deficit (secondary
      end-point) were assessed. RESULTS: Fifty-seven radial-artery related ASVC were
      collected. ASVC diagnosis was obtained by upper limb angiography in 25 patients
      (44%) and by Doppler in 32 patients (56%). Surgery was required in 6 cases (11%),
      the remaining patients receiving successful conservative management (which
      included prolonged local compression). Three patients (who received surgery)
      exhibited a mild neurological hand deficit in the follow-up. Need for surgery
      differed significantly according to timing of diagnosis as it occurred in 1 of 26
      patients (3.8%) with "very early" diagnosis, in 1 of 21 patients (4.8%) with
      "early" diagnosis, and in 4 of 10 patients (40%) with "late" diagnosis (p=0.026).
      CONCLUSIONS: ASVC are diagnosed with different timing after trans-radial
      procedures. Conservative management including local compression allows successful
      management in the majority of ASVC. Prompt recognition is pivotal as late
      diagnosis is associated to the need for surgery.

PMID- 22633678
TI  - Hybrid approaches to molecular simulation.
AB  - Molecular dynamics (MD) simulation is an established method for studying the
      conformational changes that are important for protein function. Recent advances
      in hardware and software have allowed MD simulations over the same timescales as
      experiment, improving the agreement between theory and experiment to a large
      extent. However, running such simulations are costly, in terms of resources,
      storage, and trajectory analysis. There is still a place for techniques that
      involve short MD simulations. In order to overcome the sampling paucity of short
      time-scales, hybrid methods that include some form of MD simulation can exploit
      certain features of the system of interest, often combining experimental
      information in surprising ways. Here, we review some recent hybrid approaches to
      the simulation of proteins.

PMID- 22633680
TI  - New treatment of stabilized leachate by ozone/Fenton in the advanced oxidation
      process.
AB  - Ozonation, combined with the Fenton process (O(3)/H(2)O(2)/Fe(2+)), was used to
      treat matured landfill leachate. The effectiveness of the Fenton molar ratio,
      Fenton concentration, pH variance, and reaction time were evaluated under optimum
      operational conditions. The optimum removal values of chemical oxygen demand
      (COD), color, and NH(3)-N were found to be 65%, 98%, and 12%, respectively, for
      90 min of ozonation using a Fenton molar ratio of 1 at a Fenton concentration of
      0.05 mol L(-1) (1700 mg/L) H(2)O(2) and 0.05 mol L(-1) (2800 mg/L) Fe(2+) at pH
      7. The maximum removal of NH(3)-N was 19% at 150 min. The ozone consumption for
      COD removal was 0.63 kg O(3)/kg COD. To evaluate the effectiveness, the results
      obtained in the treatment of stabilized leachate were compared with those
      obtained from other treatment processes, such as ozone alone, Fenton reaction
      alone, as well as combined Fenton and ozone. The combined method (i.e.,
      O(3)/H(2)O(2)/Fe(2+)) achieved higher removal efficiencies for COD, color, and
      NH(3)-N compared with other studied applications.

PMID- 22633679
TI  - The neuroeconomics of nicotine dependence: a preliminary functional magnetic
      resonance imaging study of delay discounting of monetary and cigarette rewards in
      smokers.
AB  - Neuroeconomics integrates behavioral economics and cognitive neuroscience to
      understand the neurobiological basis for normative and maladaptive decision
      making. Delay discounting is a behavioral economic index of impulsivity that
      reflects capacity to delay gratification and has been consistently associated
      with nicotine dependence. This preliminary study used functional magnetic
      resonance imaging to examine delay discounting for money and cigarette rewards in
      13 nicotine dependent adults. Significant differences between preferences for
      smaller immediate rewards and larger delayed rewards were evident in a number of
      regions of interest (ROIs), including the medial prefrontal cortex, anterior
      insular cortex, middle temporal gyrus, middle frontal gyrus, and cingulate gyrus.
      Significant differences between money and cigarette rewards were generally
      lateralized, with cigarette choices associated with left hemisphere activation
      and money choices associated with right hemisphere activation. Specific ROI
      differences included the posterior parietal cortex, medial and middle frontal
      gyrus, ventral striatum, temporoparietal cortex, and angular gyrus. Impulsivity
      as measured by behavioral choices was significantly associated with both
      individual ROIs and a combined ROI model. These findings provide initial evidence
      in support of applying a neuroeconomic approach to understanding nicotine
      dependence.

PMID- 22633681
TI  - Prognostic significance of smoking in patients with acute ischemic stroke within
      3 months of onset.
AB  - BACKGROUND: Various factors that have been implicated in recovery after the acute
      phase of stroke have not been well evaluated. METHODS: To identify prognostic
      factors affecting outcomes at 90 days after stroke from the viewpoint of recovery
      patterns, we enrolled 660 patients from the Edaravone and Argatroban Stroke
      Therapy for Acute Ischemic Stroke study database. Fourteen groups of patients
      were identified based on an analysis of their recovery patterns according to
      changes in their National Institutes of Health Stroke Scale scores during the
      first 21 days. These groups were then divided into 2 groups: favorable recovery
      trend (patterns 1-3; n = 486) and poor recovery trend (patterns 4-14; n = 174).
      Patterns with >80% of the patients experiencing a favorable outcome (National
      Institutes of Health Stroke Scale score of <= 4 at 90 days) were defined as the
      favorable recovery trend group, whereas patterns that included <= 80% favorable
      outcomes were defined as the poor recovery trend group. RESULTS: Using the poor
      recovery trend group, logistic regression analysis found that after controlling
      for covariates, lower scores at admission, fewer ischemic lesions, and nonsmoking
      were significant prognostic factors for a favorable outcome at 90 days.
      CONCLUSIONS: Based on a detailed analysis of the relationship between recovery
      patterns after stroke and clinical outcomes in the chronic stage of stroke,
      smoking cessation may improve the prognosis of patients after stroke.

PMID- 22633682
TI  - Multi-parameter autonomic-based pain assessment: more is more?

PMID- 22633683
TI  - VGLUT2-dependent glutamatergic transmission in primary afferents is required for
      intact nociception in both acute and persistent pain modalities.
AB  - Glutamate is an essential transmitter in pain pathways. However, its broad usage
      in the central and peripheral nervous system prevents us from designing efficient
      glutamate-based pain therapies without causing harmful side effects. The
      discovery of vesicular glutamate transporters (VGLUT1-3) has been a crucial step
      in describing specific glutamatergic neuronal subpopulations and glutamate
      dependent pain pathways. To assess the role of VGLUT2-mediated glutamatergic
      contribution to pain transmission from the entire primary sensory population, we
      crossed our Vglut2(f/f) line with the Ht-Pa-Cre line. Such Vglut2-deficient mice
      showed significantly decreased, but not completely absent, acute nociceptive
      responses. The animals were less prone to develop an inflammatory-related state
      of pain and were, in the partial sciatic nerve ligation chronic pain model, much
      less hypersensitive to mechanical stimuli and did not develop cold allodynia or
      heat hyperalgesia. To take advantage of this neuropathic pain-resistant model, we
      analyzed Vglut2-dependent transcriptional changes in the dorsal spinal cord after
      nerve injury, which revealed several novel candidate target genes potentially
      relevant for the development of neuropathic pain therapeutics. Taken together, we
      conclude that VGLUT2 is a major mediator of nociception in primary afferents,
      implying that glutamate is the key somatosensory neurotransmitter.

PMID- 22633684
TI  - Subcritical crack growth and in vitro lifetime prediction of resin composites
      with different filler distributions.
AB  - OBJECTIVES: Verify the influence of different filler distributions on the
      subcritical crack growth (SCG) susceptibility, Weibull parameters (m and
      sigma(0)) and longevity estimated by the strength-probability-time (SPT) diagram
      of experimental resin composites. METHODS: Four composites were prepared, each
      one containing 59 vol% of glass powder with different filler sizes (d(50)=0.5;
      0.9; 1.2 and 1.9 MUm) and distributions. Granulometric analyses of glass powders
      were done by a laser diffraction particle size analyzer (Sald-7001, Shimadzu,
      USA). SCG parameters (n and sigma(f0)) were determined by dynamic fatigue (10(-2)
      to 10(2) MPa/s) using a biaxial flexural device (12 * 1.2 mm; n=10). Twenty extra
      specimens of each composite were tested at 10(0) MPa/s to determine m and
      sigma(0). Specimens were stored in water at 37 degrees C for 24 h. Fracture
      surfaces were analyzed under SEM. RESULTS: In general, the composites with
      broader filler distribution (C0.5 and C1.9) presented better results in terms of
      SCG susceptibility and longevity. C0.5 and C1.9 presented higher n values
      (respectively, 31.2 +/- 6.2(a) and 34.7 +/- 7.4(a)). C1.2 (166.42 +/- 0.01(a))
      showed the highest and C0.5 (158.40 +/- 0.02(d)) the lowest sigma(f0) value (in
      MPa). Weibull parameters did not vary significantly (m: 6.6 to 10.6 and
      sigma(0):170.6 to 176.4 MPa). Predicted reductions in failure stress (P(f)=5%)
      for a lifetime of 10 years were approximately 45% for C0.5 and C1.9 and 65% for
      C0.9 and C1.2. Crack propagation occurred through the polymeric matrix around the
      fillers and all the fracture surfaces showed brittle fracture features.
      SIGNIFICANCE: Composites with broader granulometric distribution showed higher
      resistance to SCG and, consequently, higher longevity in vitro.

PMID- 22633686
TI  - Polymerase incorporation of pyrene-nucleoside triphosphates.
AB  - Pyrene-deoxynucleoside triphosphates (dPTPs), varying by the positioning of the
      aromatic system, were synthesized. Their ability to function as substrates for
      the Klenow fragment of Escherichia coli DNA polymerase I and the TdT polymerase
      was assessed. The dPTPs are all equally well tolerated by the Klenow fragment,
      and lead to elongation of up to 5 extra nucleotides of a ssDNA primer in a TdT
      mediated reaction. The tailing efficiency of the dPTPs compares favorably to
      other less drastically modified dNTPs.

PMID- 22633685
TI  - Sensitization to acute procedural pain in pediatric sickle cell disease:
      modulation by painful vaso-occlusive episodes, age, and endothelin-1.
AB  - The impact of pain early in life is a salient issue for sickle cell disease
      (SCD), a genetic condition characterized by painful vaso-occlusive episodes
      (VOEs) that can begin in the first year of life and persist into adulthood. This
      study examined the effects of age and pain history (age of onset and frequency of
      recent VOEs) on acute procedural pain in children with SCD. Endothelin-1, a vaso
      active peptide released during VOEs and acute tissue injury, and its precursor,
      Big Endothelin, were explored as markers of pain sensitization and vaso
      occlusion. Sixty-one children with SCD (ages 2 to 18) underwent venipuncture at
      routine health visits. Procedural pain was assessed via child and caregiver
      reports and observational distress. Pain history was assessed using retrospective
      chart review. Three primary results were found: 1) younger age was associated
      with greater procedural pain across pain outcomes; 2) higher frequency of VOEs
      was associated with greater procedural pain based on observational distress
      (regardless of age); and 3) age was found to moderate the relationship between
      VOEs and procedural pain for child-reported pain and observational distress for
      children 5 years of age and older. Associations between the endothelin variables
      and pain prior to venipuncture were also observed. PERSPECTIVE: For children with
      SCD, the child's age and recent pain history should be considered in procedural
      pain management. The endothelin system may be involved in preprocedure pain, but
      additional research is needed to understand the role of endothelins in pain
      sensitization.

PMID- 22633687
TI  - Finger loop inhibitors of the HCV NS5b polymerase. Part II. Optimization of
      tetracyclic indole-based macrocycle leading to the discovery of TMC647055.
AB  - Optimization of a novel series of macrocyclic indole-based inhibitors of the HCV
      NS5b polymerase targeting the finger loop domain led to the discovery of lead
      compounds exhibiting improved potency in cellular assays and superior
      pharmacokinetic profile. Further lead optimization performed on the most
      promising unsaturated-bridged subseries provided the clinical candidate 27
      cyclohexyl-12,13,16,17-tetrahydro-22-methoxy-11,17-dimethyl-10,10-dioxide-2,19
      methano-3,7:4,1-dimetheno-1H,11H-14,10,2,9,11,17-benzoxathiatetraazacyclo
      docosine-8,18(9H,15H)-dione, TMC647055 (compound 18a). This non-zwitterionic 17
      membered ring macrocycle combines nanomolar cellular potency (EC(50) of 82 nM)
      with minimal associated cell toxicity (CC(50)>20 MUM) and promising
      pharmacokinetic profiles in rats and dogs. TMC647055 is currently being evaluated
      in the clinic.

PMID- 22633688
TI  - Small molecule tertiary amines as agonists of the nuclear hormone receptor Rev
      erbalpha.
AB  - The structure-activity relationship study of a small molecule Rev-erbalpha
      agonist is reported. The potency and efficacy of the agonists in a cell-based
      assay were optimized as compared to the initial lead. Modest mouse
      pharmacokinetics coupled with an improved in vitro profile make 12e a suitable in
      vivo probe to interrogate the functions of Rev-erbalpha in animal models of
      disease.

PMID- 22633689
TI  - A heptaketide naphthaldehyde produced by a polyketide synthase from Nectria
      haematococca.
AB  - Bostrycoidin and fusarubin are biologically active fungal polyketides produced by
      Nectria haematococca. This azaanthraquinone and naphthoquinone are thought to be
      biosynthesized via formation of a C(14) heptaketide aldehyde as a common key
      intermediate. A BLAST search against the genome of N. haematococca revealed one
      candidate gene (NECHADRAFT_101778, NhPKS1), which encodes a multi-domain
      polyketide synthase (PKS) with a thiol reductase (TR) domain that would
      facilitate the reductive release of the intermediate to produce a free aldehyde.
      To investigate the possible involvement of NhPKS1 in the biosynthesis of
      bostrycoidin and fusarubin, NhPKS1 was heterologously expressed in Aspergillus
      oryzae, and shown to produce a heptaketide 3-acetonyl-1,6,8-trihydroxy-2
      naphthaldehyde as a single product. Thus, NhPKS1 catalyzes a C-2/C-11 and C-4/C-9
      aldol-type cyclization of a linear intermediate followed by a subsequent
      reductive product release to yield the naphthaldehyde. The results indicate
      NhPKS1 is the enzyme involved in the biosynthesis of bostrycoidin and fusarubin.

PMID- 22633690
TI  - Discovery and structure-activity relationship of 2,6-disubstituted pyrazines,
      potent and selective inhibitors of protein kinase CK2.
AB  - We report the discovery and structure-activity relationship of 2,6-disubstituted
      pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was
      identified, and derivatives were prepared to develop potent inhibitory activity.
      As a result, we obtained compound 7, which was the smallest unit that retained
      potency. Then, introducing an aminoalkyl group at the 6-position of the indazole
      ring resulted in improved efficacy in both enzymatic and cell-based CK2
      inhibition assays. Moreover, compound 13 showed selectivity against other kinases
      and in vivo efficacy in a rat nephritis model. These results show that 2,6
      disubstituted pyrazines have potential as therapeutic agents for nephritis.

PMID- 22633691
TI  - Design, synthesis, and evaluation of indanone derivatives as acetylcholinesterase
      inhibitors and metal-chelating agents.
AB  - A series of novel indanone derivatives was designed, synthesised and evaluated as
      potential agents for Alzheimer's disease. Among them, compound 6a, with a
      piperidine group linked to indone by a two-carbon spacer, exhibited the most
      potent inhibitor activity, with an IC(50) of 0.0018 MUM for AChE; the inhibitory
      activity of this compound was 14-fold more potent than that of donepezil.
      Furthermore, these compounds also exhibited good metal-chelating ability.

PMID- 22633692
TI  - Fused tricyclic indoles as S1P1 agonists with robust efficacy in animal models of
      autoimmune disease.
AB  - Two series of fused tricyclic indoles were identified as potent and selective
      S1P(1) agonists. In vivo these agonists produced a significant reduction in
      circulating lymphocytes which translated into robust efficacy in several rodent
      models of autoimmune disease. Importantly, these agonists were devoid of any
      activity at the S1P(3) receptor in vitro, and correspondingly did not produce
      S1P(3) mediated bradycardia in telemeterized rat.

PMID- 22633693
TI  - Emergency thoracotomy as a rescue treatment for trauma patients in Iceland.
AB  - OBJECTIVE: Emergency thoracotomy (ET) can be life-saving in highly selected
      trauma patients, especially after penetrating chest trauma. There is little
      information on the outcome of ET in European trauma centres. Here we report our
      experience in Iceland. MATERIAL AND METHODS: This was a retrospective analysis of
      all patients who underwent ET in Iceland between 2005 and 2010. Patient
      demographics, mechanism, and location of major injury (LOMI) were registered,
      together with signs of life (SOL), the need for cardiopulmonary resuscitation
      (CPR), and transfusions. Based on physiological status from injury at admission,
      the severity score (ISS), revised trauma score (RTS), and probability of survival
      (PS) were calculated. RESULTS: Of nine ET patients (all males, median age
      36years, range 20-76) there were five long-term survivors. All but one made a
      good recovery. There were five blunt traumas (3 survivors) and four penetrating
      injuries (2 survivors). The most frequent LOMI was isolated thoracic injury
      (n=6), but three patients had multiple trauma. Thoracotomy was performed in five
      patients, sternotomy in two, and two underwent both procedures. One patient was
      operated in the ambulance and the others were operated after arrival. Median ISS
      and NISS were 29 (range 16-54) and 50 (range 25-75), respectively. Median RTS was
      7 (range 0-8) with estimated PS of 85% (range 1-96%). Median blood loss was 10L
      (range 0.9-55). A median of 23 units of packed red blood cells were transfused
      (range 0-112). For four patients, CPR was required prior to transport; two others
      required CPR in the emergency room. Three patients never had SOL and all of them
      died. CONCLUSION: ET is used infrequently in Iceland and the number of patients
      was small. More than half of them survived the procedure. This is especially
      encouraging considering how severely injured the patients were.

PMID- 22633694
TI  - Experience of pre-hospital treatment of survivors of falls-related trauma by an
      Australian helicopter emergency medical service.
AB  - BACKGROUND: Greater Sydney Area Helicopter Emergency Medical Service (GSA-HEMS)
      operates a doctor and paramedic team providing pre-hospital and inter-hospital
      retrieval. Falls are an important cause of morbidity and mortality among trauma
      patients. In NSW, patients injured by falling comprise 38% of those with serious
      to critical injuries (ISS>15). The mortality of falls in this group is 15.2%,
      higher than the mortality rate for other common injury mechanisms. Mortality rate
      for high falls (>5m) is similar to that of low/medium falls. AIMS: The primary
      aim was describe the basic demographics, transportation, injured areas, treatment
      and mortality of falls survivors attended to by GSA-HEMS. The secondary aim was
      to determine if there was any association between height of fall, revised trauma
      score (RTSc) and need for advanced pre-hospital interventions. METHODS: Cases of
      trauma due to falling were identified by searching an electronic database
      covering the period June 2007 to March 2010. Hardcopy casesheets were abstracted
      using a proforma. Data was collected on demographics, timings, winch use, height
      of fall, physiologic variables, injured areas, advanced pre-hospital
      interventions and mortality at 24h. Associations between height of fall and RTSc,
      and height of fall and pre-hospital interventions were compared using Fischer's
      exact test. RESULTS: One hundred and fifty-four of 208 potential cases identified
      were cases of trauma due to falls, representing 13% of all pre-hospital trauma
      cases retrieved by the service. Median age of patients was 37, 67% of patients
      were male. Helicopter transport was use for 97% of cases, with 47% requiring
      winch extraction. High falls (>5m), which accounted for 25% of cases, were more
      likely to show non-normal RTSc. A greater proportion of high falls required
      advanced pre-hospital interventions. CONCLUSIONS: Our experience describes a HEMS
      system that is often called to falls not just based on injury severity or
      requirement for advanced pre-hospital intervention, but also due to geographical
      and topographical impediments to access and transport of the patient by ground.
      This may have implications in forward planning and activation of HEMS services.

PMID- 22633695
TI  - Functional outcomes of surgical reconstruction for posterolateral rotatory
      instability of the elbow.
AB  - BACKGROUND: The disruption or insufficiency of lateral ligament complex including
      lateral ulnar collateral ligament (LUCL) leads to posterolateral rotatory
      instability (PLRI). An accurate clinical staging is quite useful in predicting
      the prognosis. The purpose of our study is to review our experience with surgical
      reconstruction for PLRI of the elbow and to investigate the relationship between
      the clinical stage of elbow instability and the functional outcomes of PLRI.
      MATERIALS AND METHODS: Patients with PLRI of the elbow determined by fluoroscopic
      stress view under anaesthesia underwent surgical reconstruction of the LUCL with
      autogenous tendon graft. RESULTS: Thirteen of the fourteen patients (93%) were
      subjectively satisfied with the outcome of the surgery. The mean follow-up was 49
      months (range: 24-72). The results were better in patients with stage 1 or 2
      instability (group I) compared to those with stage 3 instability (group II).
      CONCLUSIONS: Reconstruction of the LUCL using an autogenous tendon graft is an
      effective method for patients with PLRI of elbow. Since better results were
      obtained in patients with stage 1 or 2 instability rather than stage 3, accurate
      clinical staging determined by fluoroscopic stress view under anaesthesia is
      important before surgery for appropriate treatment and prediction of functional
      outcomes.

PMID- 22633696
TI  - Markedly disturbed sleep in medically refractory compared to controlled epilepsy 
      a clinical and polysomnography study.
AB  - PURPOSE: To evaluate sleep disturbances or sleep related events and their
      characteristics among patients with medically refractory epilepsy, compared to
      those with controlled epilepsy. METHODS: In a prospective case-controlled study,
      patients of medically refractory and controlled epilepsy were recruited and
      history pertaining to epilepsy and sleep related events and Epworth sleepiness
      scores were recorded and all patients underwent over night polysomnography.
      RESULTS: Among 40 patients, 20 with medically refractory (Group 1) and 20 with
      controlled epilepsy (Group 2) (median age 18, range 10-35 years), the self
      reported sleep parameters in Group 1 patients were found to be significantly
      different as compared to Group 2, in terms of the duration of night time sleep,
      day time sleep, day time nap frequency, total sleep hours per day, excessive
      daytime sleepiness (EDS)(45% vs. 15%) and average sleep hours over the week prior
      to polysomnography. On PSG, Group 1 patients showed significantly less total
      sleep time [340.4 min (147-673) vs. 450.3 min (330-570)] with delayed sleep
      latency and REM latency, poor sleep efficiency [80.45 (40.5-98.0) vs. 95.45 (88.4
      99.7)] and frequent arousals and wake after sleep onset (WASO) compared to Group
      2 patients. Four patients (20%) in Group 1 compared to none in Group 2 were found
      to have mild obstructive sleep apnea. CONCLUSIONS: Our results indicate that
      medically refractory epilepsy patients believe that they spend more time
      sleeping, in contrast to the documented shorter sleep duration on
      polysomnography. This difference between perceived and actual sleep seems, by
      their data, to arise mainly from sleep fragmentation, disturbed architecture and
      the interesting finding of associated sleep apnea among the medically refractory
      epilepsy patients.

PMID- 22633697
TI  - The neural bases of difficult speech comprehension and speech production: Two
      Activation Likelihood Estimation (ALE) meta-analyses.
AB  - The role of speech production mechanisms in difficult speech comprehension is the
      subject of on-going debate in speech science. Two Activation Likelihood
      Estimation (ALE) analyses were conducted on neuroimaging studies investigating
      difficult speech comprehension or speech production. Meta-analysis 1 included 10
      studies contrasting comprehension of less intelligible/distorted speech with more
      intelligible speech. Meta-analysis 2 (21 studies) identified areas associated
      with speech production. The results indicate that difficult comprehension
      involves increased reliance of cortical regions in which comprehension and
      production overlapped (bilateral anterior Superior Temporal Sulcus (STS) and
      anterior Supplementary Motor Area (pre-SMA)) and in an area associated with
      intelligibility processing (left posterior MTG), and second involves increased
      reliance on cortical areas associated with general executive processes (bilateral
      anterior insulae). Comprehension of distorted speech may be supported by a hybrid
      neural mechanism combining increased involvement of areas associated with general
      executive processing and areas shared between comprehension and production.

PMID- 22633698
TI  - Prevalence, predictors, and perceived effectiveness of complementary, alternative
      and integrative medicine in adult-onset primary dystonia.
AB  - BACKGROUND: Complementary and Alternative Medicine (CAM) use is on the rise in
      both the US and Europe, despite questions about its safety and effectiveness, and
      lack of national standards. We aimed to determine the prevalence and predictors
      of CAM and integrative medicine use (CAM-I) and perceived effectiveness compared
      to the standard treatment of botulinum toxin injections in patients with adult
      onset primary dystonia. METHODS: This was a retrospective questionnaire study of
      389 dystonia patients examining the effects age, gender, education level and
      number of affected anatomical regions on botulinum toxin and CAM-I use and their
      perceived effectiveness. RESULTS: 53% (208) of patients reported CAM-I use, while
      90% (349) used the standard treatment (botulinum toxin), and 48% used both.
      Education was the only significant predictor of CAM-I use - individuals with
      bachelor's degrees were more likely to try CAM-I whereas those with high school
      diplomas were less likely. The mean effectiveness rate for botulinum toxin
      injections (59%) significantly exceeded that for CAM-I (28%, p < 0.0001).
      CONCLUSIONS: Our work highlights the need for scientifically sound studies to
      determine the safety, effectiveness and expense of CAM-I treatments for dystonia
      and other neurological disorders given that CAM-I use is steadily increasing,
      there is great variability in what is classified as CAM-I, and the effectiveness
      of some modalities may be significantly less than conventional medical
      treatments.

PMID- 22633699
TI  - Conversion total hip arthroplasty: a reason not to use cephalomedullary nails.
AB  - Previous studies have yet to compare outcomes of conversion to hip arthroplasty
      from screw and side plate vs cephalomedullary nail. Seventy-six patients at our
      institution underwent hip conversion after fixation failure. We performed a
      retrospective chart review to compare perioperative outcomes in these 2 groups.
      Both operative time (P = .020) and blood loss (P = .041) were significantly
      greater in patients converted from cephalomedullary nail. Greater length of stay
      in this group trended to significance (P = .101). Perioperative complications
      were similar. Recent practice patterns reveal a dramatic increase in the use of
      cephalomedullary nails despite lack of evidence suggesting their clinical
      superiority in certain fracture patterns. Our results suggest that conversion to
      total hip arthroplasty after internal fixation with cephalomedullary nail is a
      more complex procedure than is conversion from screw and side plate. The surgeon
      should consider possible later hip conversion and these results when choosing the
      appropriate fixation implant.

PMID- 22633700
TI  - Usefulness of admission matrix metalloproteinase 9 as a predictor of early
      mortality after cardiopulmonary resuscitation in cardiac arrest patients.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) have a central role in disease
      progression after ischemia-reperfusion injury. However, its prognostic
      significance in cardiac arrest (CA) patients having cardiopulmonary resuscitation
      (CPR) is unknown. The aim of this study was to investigate the relation between
      admission MMP-9 level and early mortality in CA patients. METHODS: A total of 96
      in-hospital or out-of-hospital CA patients and 40 age- and sex-matched healthy
      volunteers as the control group were evaluated prospectively. The patients were
      classified according to the CPR response into a successful group (n = 46) and a
      failed group (n = 50). RESULTS: The MMP-9 levels were detected to be 56.9 +/-
      4.3, 69.5 +/- 7.4, and 92.7 +/- 10.1 ng/mL in the control group, the successful
      CPR group (acute responders), and the failed CPR group, respectively (P < .001
      for the 2 comparisons). The MMP-9 level on admission, presence of asystole, mean
      CA duration, out-of-hospital CPR, sodium and potassium levels, and arterial pH
      were found to have prognostic significance in univariate analysis. In addition,
      MMP-9 levels were correlated with age, troponin level, and oxygen saturation. In
      multivariate logistic regression analysis with forward stepwise method, only MMP
      9 level on admission (odds ratio, 1.504; P < .001) and mean CA duration before
      CPR (odds ratio, 1.257; P = .019) remained associated with post-CPR early
      mortality after adjustment of other potential confounders. In addition, optimal
      cutoff value of MMP-9 to predict failed CPR was found as greater than 82 ng/mL,
      with 88% sensitivity and 97.8% specificity. CONCLUSIONS: High MMP-9 levels were
      associated with worse clinical and laboratory parameters, and it seems that MMP-9
      helps risk stratification in CA patients.

PMID- 22633701
TI  - Field performance of clinical case definitions for influenza screening during the
      2009 pandemic.
AB  - PURPOSE: The aim of this study was to assess the performance of 3 different
      influenza-like illness (ILI) case definitions, adopted by the European (European
      CDC), USA (USA-CDC), and Taiwan Centers for Disease Prevention and Control
      (Taiwan-CDC), as screening tools for influenza during the 2009 H1N1 pandemic.
      METHODS: From August 15 to 30, 2009, all emergency department patients with
      clinical symptoms or at epidemiologic risk for influenza were enrolled in an
      observational cohort study. Influenza diagnosis was established by positive rapid
      influenza diagnostic test or virus isolation. Sensitivity, specificity, positive
      predictive value, and negative predictive value of the European-, USA, and Taiwan
      CDC ILI case definitions for screening were determined. RESULTS: A total of 870
      patients were screened during the study period. Rapid influenza diagnostic test
      was positive in 315 patients, 273 (85.6%) of whom had fever duration less than 72
      hours. Virus isolation identified 4 more patients with influenza A initially
      negative by rapid influenza diagnostic test. The mean (SD) age of these 319
      patients was 24.3 (18.1) years. Of the 870 screened patients, 670 (77.0%), 476
      (54.7%), and 325 (37.4%) met the European-, USA-, and Taiwan-CDC ILI case
      definition, respectively. Screening sensitivity was 95%, 77.7%, and 57.7% and
      specificity was 33.4%, 58.6%, and 74.4%, respectively. Differences in sensitivity
      and specificity between any 2 of the 3 groups were statistically significant (P <
      .05). CONCLUSION: First-line physicians should recognize the advantage and
      limitation of different ILI case definitions in influenza screening, especially
      confronted by pandemic or highly pathogenic avian influenza in the future.

PMID- 22633702
TI  - Are there symptom differences in patients with coronary artery disease presenting
      to the ED ultimately diagnosed with or without ACS?
AB  - OBJECTIVES: Symptoms are compared among patients with coronary artery disease
      (CAD) admitted to the emergency department with or without acute coronary
      syndrome (ACS). Sex and age are also assessed. METHODS: A secondary analysis from
      the PROMOTION (Patient Response tO Myocardial Infarction fOllowing a Teaching
      Intervention Offered by Nurses) trial, an multicenter randomized controlled
      trial, was conducted. RESULTS: Of 3522 patients with CAD, at 2 years, 565 (16%)
      presented to the emergency department, 234 (41%) with non-ACS and 331 (59%) with
      ACS. Shortness of breath (33% vs 25%, P = .028) or dizziness (11% vs 3%, P =
      .001) were more common in non-ACS. Chest pain (65% vs 77%, P = .002) or arm pain
      (9% vs 21%, P = .001) were more common in ACS. In men without ACS, dizziness was
      more common (11% vs 2%; P = .001). Men with ACS were more likely to have chest
      pain (78% vs 64%; P = .003); both men and women with ACS more often had arm pain
      (men, 19% vs 10% [P = .019]; women, 26% vs 13% [P = .023]). In multivariate
      analysis, patients with shortness of breath (odds ratio [OR], 0.617 [confidence
      interval [CI], 0.410-0.929]; P = .021) or dizziness (OR, .0311 [CI, 0.136-0.708];
      P = .005) were more likely to have non-ACS. Patients with prior percutaneous
      coronary intervention (OR, 1.592 [CI, 1.087-2.332]; P = .017), chest pain (OR,
      1.579 [CI, 1.051-2.375]; P = .028), or arm pain (OR, 1.751 [CI, 1.013-3.025]; P
      <.042) were more likely to have ACS. CONCLUSIONS: In patients with CAD, shortness
      of breath and dizziness are more common in non-ACS, whereas prior percutaneous
      coronary intervention and chest or arm pain are important factors to include
      during ACS triage.

PMID- 22633703
TI  - Sex disparity in resuscitation efforts and outcomes in out-of-hospital cardiac
      arrest.
AB  - OBJECTIVES: The aim of this study was to investigate the association between sex,
      cardiopulmonary resuscitation efforts, and outcomes of out-of-hospital cardiac
      arrests in Korea. METHODS: We used a nationwide, out-of-hospital cardiac arrest
      cohort database in 2008. We extracted cases involving patients older than 20
      years with symptoms of presumed cardiac etiology. Potential predictors were
      collected using the Utstein style. The primary outcome was the resuscitation
      effort: basic life support and application of an automatic external defibrillator
      by emergency medical service providers, and advanced cardiac life support by
      emergency department physicians. Secondary outcomes were survival to admission
      and survival to discharge. Univariate and multivariate logistic regression models
      were applied by sex to calculate odds ratios and 95% confidence intervals
      adjusting for potential predictors. RESULTS: The total number of eligible
      patients was 13,922. Of these, 5158 patients (37.0%) were female. Females were
      also less likely than males to receive basic life support (70.8% vs 77.5%, P <
      .001) or an automatic external defibrillator (9.6% vs 14.3%, P < .001), or
      receive advanced cardiac life support (42.2% vs 49.2%, P < .001). When compared
      with males, rates of survival to admission and discharge for females were 11.8%
      (vs 12.3%, P = .43) and 3.1% (vs 1.8%, P < .001), respectively. Adjusted odds
      ratios for survival to admission and survival to discharge for females, when
      compared with males, were 1.32 (1.17-1.48) and 0.82 (0.63-1.05), respectively.
      CONCLUSIONS: Females were less likely than males to receive resuscitation. Female
      sex was associated with a higher rate of survival at admission rate, whereas it
      was not associated with survival at discharge.

PMID- 22633704
TI  - Balance of older trekkers: data on alpine accidents and performance as assessed
      using a video game machine.
AB  - The number of alpine accidents involving older trekkers has increased markedly in
      developed countries in recent years. More than 76.8% of the trekkers involved in
      alpine accidents in Japan were older than 40 years, with some experiencing a
      stroke or myocardial infarction while trekking at altitude. In the present study,
      we surveyed social trends in trekkers by interview at a popular mountain site, Mt
      Tanigawa (1963 m in altitude). The total number of trekkers interviewed was 511,
      and more than 60% of these were older than 40 years. Of trekkers older than 60
      years, 42% complained of conditions such as hypertension or diabetes. In 2
      volunteer groups (10 younger subjects and 10 older subjects), physical condition
      was assessed before and after trekking. Significant body weight loss induced by
      dehydration was observed more often in older subjects than in younger subjects (P
      < .05). Balance, as measured using the Nintendo WiiFit (Nintendo, Kyoto, Japan),
      worsened in the older group (P < .05). Local police records for 2009 showed that
      the total number of alpine accidents was 65. Injuries provoked by stumbling,
      slipping, and falling accounted for 51% of these, and 82% of casualties were
      older than 40 years, with 35% being older than 60 years. In conclusion, many
      older people involved in nonchallenging middle-altitude trekking have problems
      with regard to overall health and balance. Alpine accidents caused by myocardial
      infarction, stroke, or hypoglycemia tend to be more common in this population.
      Alpine rescue teams should be well prepared for this, and older trekkers should
      be made aware of their increased risk of injury in alpine settings.

PMID- 22633705
TI  - When health care priorities are unclear: do we obtain organs or try to save
      lives?

PMID- 22633706
TI  - Large hiatal hernia at chest radiography in a woman with cardiorespiratory
      symptoms.
AB  - Hiatal hernia (HH) is a frequent entity. Rarely, it may exert a wide spectrum of
      clinical presentations mimicking acute cardiovascular events such as angina-like
      chest pain until manifestations of cardiac compression that can include
      postprandial syncope, exercise intolerance, respiratory function, recurrent acute
      heart failure, and hemodynamic collapse. A 69-year-old woman presented to the
      emergency department complaining of fatigue on exertion, cough, and episodes of
      restrosternal pain with less than 1 hour of duration. Her medical history only
      included some episodes of bronchitis and no history of hypertension. The 12-lead
      electrocardiogram demonstrated sinus rhythm with right bundle-branch block.
      Laboratory tests, including cardiac troponin I, were within normal reference
      values. Chest radiography showed no significant pulmonary alterations and
      revealed in mediastinum a huge abnormal shadow overlapping the right heart
      compatible with a gastric bubble.The gastroscopy confirmed a large HH. A 2
      dimensional transthoracic echocardiogram, using all standard and modified apical
      and parasternal views, revealed an echolucent mass, compatible with HH,
      compressing the right atrium. Also, it showed an altered left ventricular
      relaxation and a mild increase of pulmonary artery pressure (35 mm Hg).
      Spirometry showed a mild obstruction of the small airways, whereas coronary
      angiography showed normal coronary arteries. We concluded that the patient's
      symptomatology was related to the compressive effects of the large hiatal ernia,
      a neglected cause of cardiorespiratory symptoms. The surgical repair of HH was
      indicated.

PMID- 22633707
TI  - Time to individualize duration of parenteral anticoagulation in pulmonary
      thromboembolism?

PMID- 22633708
TI  - Hyperalgesic acetabular fracture treated by transversus abdominis plane block in
      the ED.

PMID- 22633709
TI  - Paroxysmal atrial fibrillation after hyperbaric oxygen therapy.
AB  - Hyperbaric oxygen (HBO) is widely accepted as a treatment for air or gas
      embolism, carbon monoxide (CO) poisoning, clostridial myonecrosis, crush
      injuries, and thermal burns. To the best of our knowledge, after HBO therapy,
      atrial fibrillation (AF) has not been reported in the literature yet. We herein
      describe a case of AF that occurred in a woman who had taken HBO therapy for CO
      poisoning. The 78-year-old female patient was admitted to the emergency
      department with less of consciousness. Carboxyhemoglobin value at arterial blood
      gases was found to be 42.6% and was thought to be CO poisoning.
      Electrocardiography (ECG) was normal sinus rhythm. Hyperbaric oxygen therapy was
      planned. After the HBO therapy, ECG showed AF. Her rhythm returned to the normal
      sinus rhythm after amiodarone treatment. Physicians should keep in mind that HBO
      treatment could contribute to AF, and all patients' ECG should be monitored
      before and after HBO therapy.

PMID- 22633711
TI  - Complete atrioventricular block due to overdose of pregabalin.
AB  - Pregabalin, a synthetic derivate of the inhibitory neurotransmitter gamma
      aminobutyric acid, shows antiepileptic, analgesic, anticonvulsant, anxiolytic,
      and sleep-modulating activities. The major advantage of pregabalin is its
      relative reliability, easy use, high tolerance, and lack of negative interaction
      with other drugs. A 65-year-old woman with medical histories of diabetes
      mellitus, lumbar spondylosis, diabetic nephropathy, chronic renal failure, and
      anemia of chronic disease was admitted with the complaint of dizziness and
      syncope. She had been taking pregabalin 300 mg daily for 8 months.
      Electrocardiogram revealed complete atrioventricular (AV) block and right bundle
      brunch block with a heart rate of 39 per minute. Her creatinine was 1.8 mg/dL,
      and creatinine clearance was 50 mL/min. Pregabalin treatment was discontinued.
      Four days later, the complete AV block resolved spontaneously to Mobitz type II
      block and to sinus rhythm with right bundle-brunch block on the seventh day. To
      our knowledge, this is the first case of complete AV block associated with
      pregabalin. We believe that AV block occurred as a result of pregabalin's effect
      on L-type Ca++ channels in the heart. Pregabalin's different effects on
      electrocardiogram and on the heart in different individuals may have an
      association with the patterns of distribution of the L-type calcium channels in
      myocardium.

PMID- 22633712
TI  - Predicting 7-day and 3-month functional outcomes after an ED visit for acute
      nontraumatic low back pain.
AB  - BACKGROUND: Recent work has shown that two-thirds of patients report functional
      disability 1 week after an emergency department (ED) visit for nontraumatic
      musculoskeletal low back pain (LBP). Nearly half of these patients report
      functional disability 3 months later. Identifying high-risk predictors of
      functional disability at each of these 2 time points will allow emergency
      clinicians to provide individual patients with an evidence-based understanding of
      their risk of protracted symptoms. OBJECT: The aim of the present study was to
      determine whether 5 high-risk features previously identified in various primary
      care settings predict poor functional outcomes among patients in the ED. The
      hypothesized predictors are as follows: LBP-related functional disability at
      baseline, radicular signs, depression, a work-related injury, or a history of
      chronic or recurrent LBP before the index episode. METHODS: We conducted a
      prospective observational cohort study of patients in the ED with a chief
      complaint of nontraumatic LBP, which the ED attending physician classified as
      musculoskeletal. We interviewed patients in the ED before discharge and performed
      a baseline assessment of functional disability using the 24-item Roland-Morris
      questionnaire. We also trichotomized the patient's baseline history of LBP into
      chronic (defined as 30 straight days with continuous LBP or a history of acute
      exacerbations more frequently than once per week); episodic (acute exacerbations
      more frequently than once per year but less frequently than once per week), or
      rarely/never (less frequently than once per year or no history of LBP). We
      performed telephone follow-up 1 week and 3 months after ED discharge using a
      scripted closed-question data collection instrument. The primary outcome was any
      functional limitation attributable to LBP at 1 week and 3 months, defined as a
      score greater than zero on the Roland-Morris questionnaire. We used logistic
      regression, adjusted for age, sex, and educational level, to assess the
      independent association between functional disability and each of the 5
      hypothesized predictors listed above. RESULTS: We approached 894 patients for
      participation and included 556. We obtained follow-up on 97% and 92% of our
      sample at 1 week and 3 months, respectively. Two of the 5 hypothesized variables
      predicted functional disability at both time points: higher baseline Roland
      Morris score (odds ratio [OR], 4.3; 95% confidence interval [CI], 2.6-6.9) and
      chronic LBP (OR, 2.3; 95% CI, 1.1-4.8) were associated with 7-day functional
      disability. These same 2 variables predicted functional disability 3 months after
      ED discharge-higher baseline Roland-Morris score (OR, 2.3; 95% CI, 1.4-3.9) and
      chronic LBP (OR, 2.8; 95% CI, 1.5-5.2). The remaining 3 hypothesized predictors
      (depression, radicular signs, and on-the-job injury) did not predict functional
      outcome at either time point. CONCLUSIONS: Patients in the ED with worse baseline
      functional impairment and a history of chronic LBP are 2 to 4 times most likely
      to have poor short- and longer-term outcomes.

PMID- 22633713
TI  - Intranasal sufentanil for the treatment of acute pain in a winter resort clinic.
AB  - INTRODUCTION: Painful extremity injuries are common patient complaints in resort
      clinics, urgent care clinics, and emergency departments. We hypothesized that
      intranasal (IN) sufentanil could provide rapid, noninvasive, effective pain
      relief to patients presenting with acute extremity injuries. METHODS: This was an
      unblinded, nonrandomized, observational study that enrolled a convenience sample
      of patients presenting to a university-affiliated ski clinic with acute moderate
      to severe pain associated with a traumatic injury between the months of January
      and March 2011. Patients were excluded if they reported an allergy to sufentanil
      or had hypoxia, significant head injury, or hypotension. Nurses administered IN
      sufentanil using an IN atomizer device. The nurse recorded patient-reported pain
      scores (0-10 scale) on arrival and at 10, 20, and 30 minutes after administration
      of sufentanil. RESULTS: During the study period, 40 patients were enrolled; 75%
      were men. The average age was 32 years (range, 16-60 years). The average dose of
      sufentanil was 37.7 MUg. Five patients (12.5%) were given additional IN
      analgesia. Average pain on arrival was 9 (on a 10-point scale), and the mean
      reduction in pain scores was 4.7 (95% confidence interval [CI], 3.67-5.57) at 10
      minutes, 5.79 (95% CI, 4.81-6.77) at 20 minutes, and 5.74 (95% CI, 4.72-6.76) at
      30 minutes. CONCLUSION: In this limited observational trial, IN sufentanil
      provided rapid, safe, and noninvasive pain relief to patients presenting with
      acute traumatic extremity injuries. Given the ease of administration, this may
      serve as a viable option for use in other settings, such as urgent care clinics
      and emergency departments.

PMID- 22633714
TI  - Vibrio vulnificus sepsis misdiagnosed as simple deep vein thrombosis.
AB  - A 46-year-old man was transferred to the emergency department and suspected of
      having a deep vein thrombosis. The patient reported swelling and pain in both
      lower legs for 16 hours. His medical history included liver cirrhosis secondary
      to alcohol. A detailed history revealed raw fish consumption 1 day before
      admission. Within 2 hours of arrival, several hemorrhagic bullae developed in the
      color-changed lesions of both lower legs. The patient's level of consciousness
      deteriorated to a stupor. He was admitted to the intensive care unit. Despite
      intensive management with a ventilator, fluid resuscitation, vasopressors, and
      intravenous antibiotics (doxycycline, vancomycin, and a third-generation
      cephalosporin), the patient died within 23 hours of the onset of symptoms. At 1
      day after the death, a blood culture confirmed the clinical diagnosis of Vibrio
      vulnificus. Emergency physicians should consider Vibrio vulnificus infections in
      patients with sepsis and severe skin lesions and should assess (from the medical
      history) risk factors including consumption of raw seafood and direct exposure to
      seawater. Prompt diagnosis and treatment for Vibrio vulnificus infections can
      significantly improve the outcome.

PMID- 22633715
TI  - Cardiac arrest with refractory ventricular fibrillation: a successful
      resuscitation using extracorporeal membrane oxygenation.
AB  - Extracorporeal membrane oxygenation (ECMO) is a form of a mechanical
      cardiopulmonary life-support system and an adjunct to prolonged cardiac
      resuscitation. The ECMO results in good outcomes for patients with in-hospital
      cardiac arrest. We present a case of a 52-year-old man with out-of-hospital
      cardiac arrest caused by refractory ventricular fibrillation. The patient was
      referred to our emergency department with suspected acute coronary syndrome.
      Cardiac arrest with ventricular fibrillation was refractory to conventional
      cardiopulmonary resuscitation. In this case, the ECMO-cardiopulmonary
      resuscitation provided cardiopulmonary life support for out-of-hospital cardiac
      arrest, achieving a sustained return of spontaneous circulation that allowed
      prompt percutaneous coronary intervention and a good recovery.

PMID- 22633716
TI  - Cardiopulmonary resuscitation for cardiac arrest: the importance of uninterrupted
      chest compressions in cardiac arrest resuscitation.
AB  - Over the last decade, the importance of delivering high-quality cardiopulmonary
      resuscitation (CPR) for cardiac arrest patients has become increasingly
      emphasized. Many experts are in agreement concerning the appropriate compression
      rate, depth, and amount of chest recoil necessary for high-quality CPR. In
      addition to these factors, there is a growing body of evidence supporting
      continuous or uninterrupted chest compressions as an equally important aspect of
      high-quality CPR. An innovative resuscitation protocol, called cardiocerebral
      resuscitation, emphasizes uninterrupted chest compressions and has been
      associated with superior rates of survival when compared with traditional CPR
      with standard advanced life support. Interruptions in chest compressions during
      CPR can negatively impact outcome in cardiac arrest; these interruptions occur
      for a range of reasons, including pulse determinations, cardiac rhythm analysis,
      electrical defibrillation, airway management, and vascular access. In addition to
      comparing cardiocerebral resuscitation to CPR, this review article also discusses
      possibilities to reduce interruptions in chest compressions without sacrificing
      the benefit of these interventions.

PMID- 22633717
TI  - Postintubation hemodynamic effects of intravenous lidocaine in severe traumatic
      brain injury.
AB  - BACKGROUND: The risks of intravenous (IV) lidocaine before rapid sequence
      induction (RSI) have become a great concern. No study has investigated the
      hemodynamic effects of IV lidocaine during endotracheal intubation in patients
      with severe traumatic brain injury. OBJECTIVE: We investigated whether the use of
      IV lidocaine before RSI was associated with postintubation hemodynamic changes in
      patients with severe traumatic brain injury. METHODS: In this retrospective
      cohort study, adults who presented with isolated traumatic brain injury and
      definite intracranial hemorrhage were included. Patients who presented with other
      major injuries received prehospital intubation, had initial mean arterial
      pressure (MAP) less than 70 mm Hg, and/or had incomplete medical records were
      excluded. RESULTS: A total of 101 patients (82.2% men; mean age, 48.6 +/- 19.6
      years) were enrolled. Forty-six patients received IV lidocaine in addition to RSI
      before intubation (group 1), and 55 received RSI without IV lidocaine before
      intubation (group 2). There were no significant intergroup differences in
      baseline characteristics, the number of RSI doses, or the RSI dose used, with the
      exception of sex, diagnosis of subarachnoid hemorrhage, and diagnosis of subdural
      hemorrhage. Our results demonstrated no significant intergroup differences in MAP
      changes or the proportion of patients with hypotension (MAP <70 mm Hg) after
      intubation. Intravenous lidocaine remained unrelated to significant hypotension
      after adjusting for variables by logistic regression analysis. CONCLUSION:
      Intravenous lidocaine in addition to RSI before endotracheal intubation was not
      associated with significant hemodynamic changes in patients with severe traumatic
      brain injury.

PMID- 22633718
TI  - Takotsubo cardiomyopathy: a hidden enemy of the hypovolemic patient?
AB  - Takotsubo cardiomyopathy (TCM) is an underrecognized transient left ventricular
      dysfunction that mimics clinically an acute coronary syndrome. It has been linked
      to emotional stress and several clinical entities that provoke a catecholamine
      surge in the blood stream. We investigated the case of a young female patient who
      was admitted to the intensive care unit after a significant blood loss due to
      miscarriage. The patient was fully monitored and was treated for the hypovolemia.
      A dramatic aggravation of her clinical status was directly linked to the
      appearance of TCM 1 hour after her admission. This study sought to assess the
      appearance of TCM in a hypovolemic patient. We found no reports in the literature
      linking these 2 clinical entities. The blood loss and the pathophysiology of
      hypovolemia, especially through the excess of catecholamines that are released in
      the blood stream, seem to provoke the appearance of a subclinical form of TCM. As
      a result, TCM worsened further the general condition of the patient. There is a
      high possibility that TCM and hypovolemia can be closely related, and therefore,
      the treatment of hypovolemia can be adjusted to new standards. Because it has
      already been proved that TCM can be induced by emotional stress and various
      pathological entities, further investigations are necessary.

PMID- 22633719
TI  - Syncopal storm caused by glossopharyngeal neuralgia.
AB  - We report a rare case presenting with up to 50 episodes of syncopes per day in a
      54-year-old man with the ultimate diagnosis of idiopathic glossopharyngeal
      neuralgia. All episodes were started with a severe pain sensation in the right
      side of the throat followed by asystole and then very slow ventricular escape
      beats. The patient was successfully treated with the combination of
      carbamazepine, gabapentin, and dual-chamber pacemaker implantation.

PMID- 22633720
TI  - Cardiac troponin: a critical review of the case for point-of-care testing in the
      ED.
AB  - The measurement of cardiac troponin concentrations in the blood is a key element
      in the evaluation of patients with suspected acute coronary syndromes, according
      to current guidelines, and contributes importantly to the ruling in or ruling out
      of acute myocardial infarction. The introduction of point-of-care testing for
      cardiac troponin has the potential to reduce turnaround time for assay results,
      compared with central laboratory testing, optimizing resource use. Although, in
      general, many point-of-care cardiac troponin tests are less sensitive than
      cardiac troponin tests developed for central laboratory-automated analyzers,
      point-of-care systems have been used successfully within accelerated protocols
      for the reliable ruling out of acute coronary syndromes, without increasing
      subsequent readmission rates for this condition. The impact of shortened assay
      turnaround times with point-of-care technology on length of stay in the emergency
      department has been limited to date, with most randomized evaluations of this
      technology having demonstrated little or no reduction in this outcome parameter.
      Accordingly, the point-of-care approach has not been shown to be cost-effective
      relative to central laboratory testing. Modeling studies suggest, however, that
      reengineering overall procedures within the emergency department setting, to take
      full advantage of reduced therapeutic turnaround time, has the potential to
      improve the flow of patients through the emergency department, to shorten
      discharge times, and to reduce cost. To properly evaluate the potential
      contribution of point-of-care technology in the emergency department, including
      its cost-effectiveness, future evaluations of point-of-care platforms will need
      to be embedded completely within a local decision-making structure designed for
      its use.

PMID- 22633721
TI  - Secondary chordae rupture due to low-tension electricity trauma.
AB  - The most frequent cardiac pathologies caused by electric shock are arrhythmias
      with a wide clinical picture ranging from sinus tachycardia to asystole. Cardiac
      mechanical complications secondary to electric shock have rarely been reported.
      Despite the use of electrocardiography and cardiac monitorization in evaluating
      dysrhythmias and in the patients' follow-up, there is still no consensus on how
      to assess patients against probable mechanical complications and how to follow up
      these patients. In this study, we have presented the rupture in the secondary
      chordae of the mitral anterior leaflet caused by low-voltage electrical trauma.
      To our knowledge, this is the first cardiac mechanical complication reported as a
      consequence of low-tension electrical trauma.

PMID- 22633722
TI  - Intravenous contrast alone vs intravenous and oral contrast computed tomography
      for the diagnosis of appendicitis in adult ED patients.
AB  - OBJECTIVE: When the diagnosis of appendicitis is uncertain, computerized
      tomography (CT) scans are frequently ordered. Oral contrast is often used but is
      time consuming and of questionable benefit. This study compared CT with
      intravenous contrast alone (IV) to CT with IV and oral contrast (IVO) in adult
      patients with suspected appendicitis. METHODS: This is a prospective, randomized
      study conducted in a community teaching emergency department (ED). Patients with
      suspected appendicitis were randomized to IV or IVO CT. Scans were read
      independently by 2 designated study radiologists blinded to the clinical outcome.
      Surgical pathology was used to confirm appendicitis in patients who went to the
      operating room (OR). Discharged patients were followed up via telephone. The
      primary outcome measure was the diagnosis of appendicitis. Secondary measures
      included time from triage to ED disposition and triage to OR. RESULTS: Both IV (n
      = 114) and IVO (n = 113) scans had 100% sensitivity (95% confidence interval
      [CI], 89.3-100 and 87.4-100, respectively) and negative predictive value (95% CI,
      93.7-100 and 93.9-100, respectively) for appendicitis. Specificity of IV and IVO
      scans was 98.6 and 94.9 (95% CI, 91.6-99.9 and 86.9-98.4, respectively),
      respectively, with positive predictive values of 97.6 and 89.5 (95% CI, 85.9-99.9
      and 74.2-96.6). Median times to ED disposition and OR were 1 hour and 31 minutes
      (P < .0001) and 1 hour and 10 minutes (P = .089) faster for the IV group,
      respectively. Patients with negative IV scans were discharged nearly 2 hours
      faster (P = .001). CONCLUSIONS: Computerized tomography scans with intravenous
      contrast alone have comparable diagnostic performance to IVO scans for
      appendicitis in adults. Patients receiving IV scans are discharged from the ED
      faster than those receiving IVO scans.

PMID- 22633723
TI  - Therapy and outcomes in massive pulmonary embolism from the Emergency Medicine
      Pulmonary Embolism in the Real World Registry.
AB  - STUDY AIM: Clinical guidelines recommend fibrinolysis or embolectomy for acute
      massive pulmonary embolism (PE) (MPE). However, actual therapy and outcomes of
      emergency department (ED) patients with MPE have not previously been reported. We
      characterize the current management of ED patients with MPE in a US registry.
      METHODS: A prospective, observational, multicenter registry of ED patients with
      confirmed PE was conducted from 2006 to 2008. Massive PE was defined as PE with
      an initial systolic blood pressure less than 90 mm Hg. We compared inpatient and
      30-day mortality, bleeding complications, and recurrent venous thromboembolism.
      RESULTS: Of 1875 patients enrolled, 58 (3.1%) had MPE. There was no difference in
      frequency of parenteral anticoagulation (98.3% [95% confidence interval {CI},
      90.5-101.6] vs 98.5% [95% CI, 97.9-99.1], P = .902) between patients with and
      without MPE. Fibrinolytic therapy and embolectomy were infrequently used but were
      used more in patients with MPE than in patients without MPE (12.1% [95% CI, 3.7
      20.5] vs 2.4% [95% CI, 1.7-3.1], P < .001, and 3.4% [95% CI, 0.0-8.1] vs 0.7%
      [95% CI, 0.3-1.1], P = .022, respectively). Comparison of outcomes revealed
      higher all-cause inpatient mortality (13.8% [95% CI, 4.9-22.7] vs 3.0% [95% CI,
      2.2-3.8], P < .001), higher risk of inpatient bleeding complications (10.3% [95%
      CI, 2.5-18.1] vs 3.5% [95% CI, 2.7-4.3], P = .007), and a higher 30-day mortality
      (14.0% [95% CI, 4.4-23.6] vs 1.8% [95% CI, 1.2-2.4], P < .001) for patients with
      MPE. CONCLUSIONS: In a contemporary registry of ED patients, MPE mortality was 4
      fold higher than patients without MPE, yet only 12% of the MPE cohort received
      fibrinolytic therapy. Variability exists between the treatment of MPE and current
      recommendations.

PMID- 22633724
TI  - Characteristics of and outcome for patients with chest pain in relation to
      transport by the emergency medical services in a 20-year perspective.
AB  - AIM: The aims of this study were to describe the characteristics of and outcome
      of patients with chest pain in relation to transport by the emergency medical
      services (EMS) and to describe possible changes in this relationship in a 20-year
      perspective. METHODS: In the 2 periods, 1986 to 1987 and 2008, all patients with
      chest pain admitted to hospitals in Gothenburg, Sweden, were retrospectively
      evaluated in terms of previous history, final diagnosis, and mortality. P values
      were age adjusted. RESULTS: In 1986 to 1987 and 2008, 34% of 4270 patients with
      chest pain and 39% of 2286 patients, respectively, were transported to the
      hospital by the EMS (P = .0001). In both periods, patients who used EMS were
      older and had a higher prevalence of previous cardiovascular diseases and more
      often had a final diagnosis of acute myocardial infarction (AMI) than those who
      did not use EMS. The EMS users were more frequently hospitalized in 1986 to 1987
      than in 2008 (P < .0001). Emergency medical service use was related to a
      significantly higher age-adjusted 1-year mortality in both periods for all
      patients with chest pain as well as for those hospitalized. Among hospitalized
      patients with myocardial ischemia and among patients with a final diagnosis of
      AMI, EMS use was associated with a higher 30-day mortality in 1986 to 1987.
      Regardless of the use of EMS, there was a decrease in the proportion of patients
      developing AMI as well as the rate of death at 30 days and 1 year in 2008 as
      compared with 1986 to 1987. CONCLUSIONS: For 20 years, the proportion of patients
      with chest pain using the EMS increased. EMS users were more frequently
      hospitalized in 1986 to 1987 than in 2008. In overall terms, mortality was higher
      among EMS users than among nonusers in both periods. Among hospitalized patients
      with myocardial ischemia and among patients with a final diagnosis of AMI, EMS
      use was associated with a higher 30-day mortality only in 1986 to 1987.

PMID- 22633725
TI  - Methylene blue for the treatment of refractory anaphylaxis without hypotension.
AB  - Anaphylaxis is a life-threatening reaction treated primarily with epinephrine.
      Methylene blue, a competitive inhibitor of guanylate cyclase, interferes with the
      vasodilatory actions of nitric oxide. It has recently been proposed by the Joint
      Taskforce on Practice Parameters as an alternative treatment for anaphylaxis with
      hypotension that is not responsive to classical therapy. Little evidence supports
      its use in normotensive patients with refractory anaphylaxis. We present the case
      of a 43-year-old woman with severe anaphylaxis unresponsive to epinephrine.
      Physical examination revealed marked respiratory distress, raised oral lesions,
      and altered mental status but lacked hypotension. After infusion of methylene
      blue, symptom resolution occurred almost immediately, and intubation was spared.
      Side effects were minimal. We propose methylene blue as a safe treatment option
      for refractory anaphylaxis, whether with or without hypotension.

PMID- 22633726
TI  - Extravasation of contrast media managed with recombinant human hyaluronidase.
AB  - In minor cases, contrast extravasation may cause pain, swelling, and localized
      erythema. However, in more severe cases, extensive tissue and skin necrosis,
      ulceration, and compartment syndrome may occur, often necessitating a surgical
      consultation. Hyaluronidase has been used successfully in the management of
      extravasated contrast media in several reports. In addition, recombinant human
      hyaluronidase is approved for use as an adjunct in subcutaneous urography for
      improving resorption of radiopaque agents. In this case, a 57-year-old white
      female admitted for a chronic obstructive pulmonary disease exacerbation with
      pneumonitis and hypoxic respiratory failure experienced contrast extravasation
      during a computed tomographic scan of her chest. Approximately 100 mL of
      iodinated contrast extravasated into the right antecubital fossa, infiltrating
      approximately the distal two-thirds of the upper arm. Five 150-U vials of
      recombinant human hyaluronidase were injected in 150-U aliquots in a circle
      around the extravasation site using a 27-gauge needle 1 hour after the
      extravasation occurred. In a follow-up 4 hours later, marked improvement was
      observed. Sixteen hours after hyaluronidase treatment, the tissue had reverted to
      a near-normal state with no pain, erythema, swelling, or tenderness noted.
      Hyaluronidase successfully treated this extravasation of a large volume of
      iodinated contrast and appears to be a reasonable treatment option for more
      extensive subcutaneous contrast media extravasations.

PMID- 22633727
TI  - Carotid artery dissection presenting with isolated headache and Horner syndrome
      after minor head injury.
AB  - A woman aged 31 years presented to the emergency department after a minor head
      injury. She reported mild headache and a metallic taste in her mouth. Full
      neurologic examination was remarkable only for left-sided Horner syndrome. Left
      internal carotid artery dissection was confirmed on magnetic resonance imaging.
      She was treated with aspirin. Symptoms and signs persisted 3 months later, but
      there was no additional neurologic deficit. We stress the importance of early
      detection of Horner syndrome to minimize the risk of disabling stroke.

PMID- 22633728
TI  - Olanzapine in ED patients: differential effects on oxygenation in patients with
      alcohol intoxication.
AB  - INTRODUCTION: Agitation has significant consequences for patients and staff. When
      verbal techniques fail, expert guidelines recommend the use of second-generation
      antipsychotics (SGAs). Perhaps out of familiarity with haloperidol and
      benzodiazepines, emergency department (ED) clinicians often pair SGAs with
      benzodiazepines as well. Use of SGAs such as olanzapine in alcohol-intoxicated
      (ETOH+) patients or with benzodiazepines is not well studied and may be
      associated with vital sign abnormalities. METHODS: This is a structured chart
      review of all patient visits who received either oral or intramuscular (i.m.)
      olanzapine in an academic ED from 2004 to 2010 and who had systolic blood
      pressure, heart rate, and oxygen saturation documented before medication
      administration and within 4 hours afterwards. RESULTS: Four hundred eighty-two
      patient visits received olanzapine; 275 patient visits (225 oral, 50 i.m.) had
      vital signs documented. Neither route of administration, concurrent
      benzodiazepines, nor ingestion of ETOH were associated with significant decreases
      in systolic BP or heart rate (P = ns for all comparisons). Decreases in oxygen
      saturations, however, were significantly larger in ETOH+ patients who received
      i.m. olanzapine or i.m. olanzapine + benzodiazepines. Route of administration,
      concurrent benzodiazepines, nor ingestion of ETOH was associated with significant
      decreases in systolic blood pressure or heart rate (p = ns for all comparisons).
      Decreases in oxygen saturations, however, were significantly larger in ETOH+
      patients who received i.m. olanzapine or i.m. olanzapine + benzodiazepines.
      CONCLUSIONS: Oral olanzapine was not associated with significant vital sign
      changes in ED patients. Intramuscular olanzapine also was not associated with
      vital sign changes in ETOH- patients. In ETOH+ patients, i.m. olanzapine was
      associated with significant oxygen desaturations. In ETOH+ ED patients, oral
      olanzapine (with or without benzodiazepines) or haloperidol may be safer choices.
      ETOH+ patients may have differential effects with the use of i.m. SGAs such as
      olanzapine and should be studied separately in drug trials.

PMID- 22633729
TI  - X-ray-negative posterior sternoclavicular dislocation after minor trauma.
AB  - Posterior sternoclavicular dislocation is a rare injury that must be recognized
      by the emergency physician because failure to rapidly reduce can lead to serious
      vascular complications. A high index of suspicion must be maintained in the
      appropriate setting because these injuries are difficult to detect on physical
      examination as well as on plain radiography. We present a case of a 19-year-old
      man with an isolated posterior sternoclavicular dislocation, in the setting of
      minor blunt trauma. The correct diagnosis required multiple imaging modalities
      over 2 emergency department visits and was ultimately successfully managed with
      intraoperative reduction.

PMID- 22633730
TI  - Traumatic mediastinal hematoma: a potentially fatal condition that may be
      overlooked by traditional Focused Assessment with Sonography for Trauma.
AB  - Mediastinal hematoma is an uncommon finding in blunt chest trauma. It may be
      caused by aortic injury, by mediastinal vascular injury such as aortic injury,
      and by fractures of the sternum and vertebral column. A huge mediastinal hematoma
      can result in extrapericardial cardiac tamponade by compressing the adjacent
      organs. Although Focused Assessment with Sonography for Trauma (FAST) can
      reliably assess the presence of pericardial effusion in the subxiphoid view, it
      may overlook mediastinal hematoma. We present a 67-year-old male victim of blunt
      chest trauma complicated with expanding anterior mediastinal hematoma that was
      undetectable with standard FAST protocol. The large mediastinal hematoma can only
      be seen in the parasternal long-axis view. When ultrasound is used to assess for
      anteriorly located mediastinal hematoma, the transducer should be positioned in
      the parasternal or precordial area to scan into the pericardium and mediastinum.
      However, these 2 views (parasternal and precordial) are not included in emergency
      department's traditional FAST examination. The subxiphoid view of FAST can easily
      miss a mediastinal hematoma. For trauma patients with probable mediastinal
      injuries, we suggest doing an extended FAST with parasternal long-axis view.
      Alternatively, one should consider lowering the threshold of thoracic computed
      tomographic scan in patients with persistent symptoms because a missed
      mediastinal hematoma could be insidious and fatal.

PMID- 22633731
TI  - Occipital lobe epilepsy presenting as Charles Bonnet syndrome.
AB  - Charles Bonnet syndrome describes visual field or acuity loss with complex
      hallucinations. This typically occurs in the elderly with preexisting visual
      impairment. We describe a patient who presented to the emergency department with
      acute hemianopsia and intermittent complex hallucinations. A 57-year-old man was
      referred for visual field loss and hallucinations. Chief complaint was "seeing
      little heads of people" and a right-sided visual loss. The patient was alert,
      oriented, and able to repeat and name and had fluent speech. On cranial nerve
      examination, he had 20/20 visual acuity and right homonymous hemianopsia. The
      patient had normal laboratory examination and electrocardiogram results. Results
      of computed tomography and magnetic resonance imaging of the head with contrast
      were negative. Standard 30-minute electroencephalography revealed near-continuous
      epileptiform discharges in the left occipital lobe. To our knowledge, this is the
      first case report of new-onset seizure presenting as Charles Bonnet syndrome.

PMID- 22633732
TI  - Predictors of patient length of stay in 9 emergency departments.
AB  - OBJECTIVES: Prolonged emergency department (ED) length of stay (LOS) is linked to
      adverse outcomes, decreased patient satisfaction, and ED crowding. This
      multicenter study identified factors associated with increased LOS. METHODS: This
      retrospective study included 9 EDs from across the United States. Emergency
      department daily operational metrics were collected from calendar year 2009. A
      multivariable linear population average model was used with log-transformed LOS
      as the dependent variable to identify which ED operational variables are
      predictors of LOS for ED discharged, admitted, and overall ED patient categories.
      RESULTS: Annual ED census ranged from 43,000 to 101,000 patients. The number of
      ED treatment beds ranged from 27 to 95. Median overall LOS for all sites was 5.4
      hours. Daily percentage of admitted patients was found to be a significant
      predictor of discharged and admitted patient LOS. Higher daily percentage of
      discharged and eloped patients, more hours on ambulance diversion, and weekday
      (vs weekend) of patient presentation were significantly associated with prolonged
      LOS for discharged and admitted patients (P < .05). For each percentage of
      increase in discharged patients, there was a 1% associated decrease in overall
      LOS, whereas each percentage of increase in eloped patients was associated with a
      1.2% increase in LOS. CONCLUSIONS: Length of stay was increased on days with
      higher percentage daily admissions, higher elopements, higher periods of
      ambulance diversion, and during weekdays, whereas LOS was decreased on days with
      higher numbers of discharges and weekends. This is the first study to demonstrate
      this association across a broad group of hospitals.

PMID- 22633733
TI  - Prognostic significance of reciprocal ST-segment depression in patients with
      acute STEMI undergoing immediate invasive intervention.
AB  - PURPOSES: Reciprocal changes are frequent in patients with acute ST-segment
      elevation myocardial infarction (STEMI). However, their prognostic significance
      is not clear in patients undergoing immediate invasive intervention. BASIC
      PROCEDURE: We retrospectively examined 165 consecutive patients with STEMI
      receiving immediate invasive intervention. The first electrocardiography taken in
      the emergency department was analyzed. Patients were assigned to 2 groups: with a
      reciprocal change (group I, n = 100) and without a reciprocal change (group II, n
      = 65). MAIN FINDINGS: Electrocardiographs revealed that more anterolateral and
      inferior STEMI occurred in group I and more anterior STEMI occurred in group II.
      In the emergency department, group I had lower systolic and diastolic blood
      pressures, higher ventricular tachycardia and fibrillation rates, and higher
      cardiopulmonary resuscitation rates than did group II. Upon admission, peak
      troponin I levels were significantly higher in group I, and more group I patients
      required intra-aortic balloon pumping support. This unstable hemodynamic
      condition in group I patients was reflected by their higher in-hospital mortality
      rate. Multivariate analysis showed that age (odds ratio [OR], 1.103; 95%
      confidence interval [CI], 1.022-1.190; P = .012), Killip class (OR, 2.785; 95%
      CI, 1.049-7.400; P = .040), and reciprocal change (OR, 9.553; 95% CI, 1.146
      79.608; P = .037) remained as independent predictors of in-hospital mortality.
      Actuarial freedom from all-cause mortality was worse in group I (P = .046).
      PRINCIPAL CONCLUSIONS: The data suggest that patients with STEMI with reciprocal
      electrocardiographic changes have unstable hemodynamic status and poorer
      outcomes. Further prospective studies using a larger patient population are
      needed.

PMID- 22633734
TI  - Comment on "Hyperacute rejection from a donor who died of carbamate intoxication
      a case report".

PMID- 22633735
TI  - Comment on "Lipid 20% emulsion ameliorates the symptoms of olanzapine toxicity in
      a 4-year-old".

PMID- 22633736
TI  - Nine modalities to report D-dimer concentration: how many is too many?

PMID- 22633737
TI  - [Unknown congenital elliptocytosis as triggering factor of heart failure in a
      nonagenarian woman].

PMID- 22633738
TI  - Patterns of delayed detection and persistence of bovine tuberculosis in confirmed
      and unconfirmed herd breakdowns in cattle and cattle herds in Great Britain.
AB  - Approximately 1500/6000 cattle farms that were depopulated during the foot and
      mouth epidemic in GB in 2001 had been repopulated and subjected to two
      unrestricted (herd considered free from bovine tuberculosis (bTB)) herd tests.
      Factors associated with herd breakdown(s) (HBD) and individual cattle reactor
      status at the second test were investigated. There were 96 HBD in total, with a 3
      fold increased risk of HBD in herds that had had a HBD at the first test after
      restocking. Two mixed effect models were used to investigate factors associated
      with 324/246,060 reactor cattle at the second bTB test; 228 reactors were at
      confirmed HBD and 96 at unconfirmed HBD; 253 (79%) reactors at the second test
      were present and test negative at the first test. In confirmed HBD, the odds of
      cattle reacting were higher if the restocked farm had a history of bTB before
      2001 and if the source and restocked farms were high frequency tested (HFT) farms
      (routine bTB tests at >=1 per 2 years). Reacting cattle were more likely to have
      been born on the restocked farm before the first test after FMD and less likely
      to have been purchased from a low frequency tested (LFT) farm (routine bTB tests
      at 3-4 year intervals) after the first test compared with a baseline of cattle
      purchased from a LFT farm before the first test. Unconfirmed HBD at the second
      test was more likely when the first test was a confirmed HBD and when there was a
      history of bTB in the restocked farm. In contrast to confirmed HBD, cattle
      purchased from a LFT farm after the first test were at increased risk of reacting
      at an unconfirmed HBD at the second test. We conclude that a farm history of bTB
      suggests persistence of bTB on the farm. Confirmed tests indicate exposure to bTB
      for some time indicated by the increased risk from HFT source and restocked farms
      and a farm history of bTB. The risks for reactors are related to the farm and
      herd and duration of exposure to these risks. Therefore, the spread of bTB to
      naive herds would be reduced if farmers only introduced cattle known not to have
      been in herds and on farms exposed to bTB. Management of bTB on farms with bTB is
      complicated because there is undisclosed infection in cattle and environmental
      contamination.

PMID- 22633739
TI  - Age trends in prevalence of cardiovascular risk factors in Roma minority
      population of Croatia.
AB  - The Roma (Gypsy) are the largest European minority population characterized by
      poverty, social exclusion as well as by numerous life-style and cultural
      specificities, which all could have an adverse impact on their cardiovascular
      health. This study assesses the prevalence of cardiovascular diseases (CVD) risk
      factors in community-based sample of 430 adult Roma, living in rural area of
      Croatia, by providing the actual and age-adjusted estimates using the European
      standard population. The most prominent classical CVD risk phenotypes (blood
      pressure, obesity, smoking, glucose and lipid profile) were selected, and the
      standard risk cut-offs were applied. The study has shown that compared to general
      population of Croatia, the Roma population bears a high CVD risk factors load
      related to smoking and high glucose level. The CVD risk factors prevalence in
      Roma also showed important sex and age patterns, the most imposing of which are
      the findings of higher prevalence of CVD risks in women (especially obesity and
      triglyceride levels) and the trend of higher body mass index (BMI) level in
      younger age group (18-34 years) which both stand in contrast to the trends
      characterizing the general population of Croatia. These findings are complemented
      by the trend of decreased risk in the oldest age group (65+ years) for all
      investigated CVD risk factors (with exception of triglycerides level) compared to
      the 50-64 age group. We conclude that the age and sex CVD risks pattern point to
      the health transition of this rural Roma population. As we expect the proportion
      of CVD in the Roma minority of Croatia to increase in the future along with
      further modernization of their lifestyle, the CVD prevention measures in this
      population are urgent and should be primarily targeted at women and at the
      younger segment of this population.

PMID- 22633740
TI  - SU-8 based microprobes with integrated planar electrodes for enhanced neural
      depth recording.
AB  - Here, we describe new fabrication methods aimed to integrate planar tetrode-like
      electrodes into a polymer SU-8 based microprobe for neuronal recording
      applications. New concepts on the fabrication sequences are introduced in order
      to eliminate the typical electrode-tissue gap associated to the passivation
      layer. Optimization of the photolithography technique and high step coverage of
      the sputtering process have been critical steps in this new fabrication process.
      Impedance characterization confirmed the viability of the electrodes for reliable
      neuronal recordings with values comparable to commercial probes. Furthermore, a
      homogeneous sensing behavior was obtained in all the electrodes of each probe.
      Finally, in vivo action potential and local field potential recordings were
      successfully obtained from the rat dorsal hippocampus. Peak-to-peak amplitude of
      action potentials ranged from noise level to up to 400-500 MUV. Moreover, action
      potentials of different amplitudes and shapes were recorded from all the four
      recording sites, suggesting improved capability of the tetrode to distinguish
      from different neuronal sources.

PMID- 22633741
TI  - Con: continuous cardiac output and SvO2monitoring are not routine in off-pump
      coronary artery bypass grafting.

PMID- 22633742
TI  - Pro: continuous cardiac output and SvO2monitoring should be routine during off
      pump coronary artery bypass graft surgery.

PMID- 22633743
TI  - Continuous mechanical chest compression using the LUCAS-2 device as a bridge to
      emergency aortic valve surgery.

PMID- 22633744
TI  - Stress-induced cardiomyopathy after patent foramen ovale closure: what role did
      anesthesia play?

PMID- 22633745
TI  - Is the long sarcomere length responsible for non-traumatic supraspinatus
      tendinopathy? Potential novel pathophysiology and implications for physiotherapy.
AB  - Several theories have been proposed to explain the mechanism of non-traumatic
      supraspinatus tendinopathy, which causes rotator cuff tendinitis and rotator cuff
      ruptures. However, these theories have not addressed all potential causes of
      rotator cuff tendinopathy. We propose that the microanatomy of the supraspinatus
      muscle and its response to gravity is the mechanism that responsible for non
      traumatic supraspinatus tendinopathy and rotator cuff tears. Gravity causes
      chronic traction to the supraspinatus muscle, which results in elongation in the
      sarcomere length. Elongated sarcomere length causes compression on the micro
      vessels in the muscle which compromises internal microcirculation of the muscle
      and tendon. Poor microcirculation triggers ischemia and ischemia triggers
      inflammation process in the muscle and the tendon. This results in a higher
      incidence of tendinopathy. We also propose a new physiotherapeutic approach that
      may provide improved healing for rotator cuff tendinopathy.

PMID- 22633746
TI  - Angiopoietins as promising biomarkers and potential therapeutic targets in brain
      injury.
AB  - Traumatic brain injury (TBI) and sub-arachnoid hemorrhage (SAH) are major causes
      of long-term disability, mortality, and enormous economic costs to society. The
      full spectrum of neurological damage created by TBI or SAH is not usually
      manifested at the time of injury, but evolves gradually over the course of hours
      to days (or weeks) following these injuries. Angiopoietins, important regulators
      of vascular structure and function, are hallmark indicators of vascular injury
      and may therefore represent promising targets in the treatment of SAH and TBI. In
      animal models and human tissues, normal intracerebral and pial vessels show
      strong expression of Angiopoietin-1 (Ang-1), but only minimal expression or
      presentation of Angiopoietin-2 (Ang-2). After several types of neurotrauma, the
      ratios of Ang-1 and Ang-2 expression in brain microvessel are disturbed and
      appear to contribute to the remarkable loss of blood-brain barrier (BBB) in these
      injuries. Angiopoietins levels, and perhaps more importantly, Angiopoietin ratios
      (1:2) may have novel and important diagnostic and prognostic uses in TBI and SAH
      brain injury. Ang-1/2 evaluation in plasma, serum and cerebrospinal fluid may
      provide new therapeutic modalities which can modify 'secondary' forms of brain
      injury after TBI and SAH.

PMID- 22633748
TI  - How do lung cancer specialists follow their patients with stage III non-small
      cell lung cancer (NSCLC) after definitive treatment? A short report.
AB  - Although pretreatment evaluations are well defined for the diagnosis of radically
      treatable NSCLC, we have very little data about the follow-up of these patients
      after completion of therapy, especially for stage III patients. No documented
      standards for surveillance were set in the NCCN, ACCP or ESMO guidelines. In
      order to determine the standard practice patterns of lung specialists, a survey
      was done. Physicians were asked which tests they do for pretreatment evaluation
      and also on asymptomatic patients during their post-treatment follow-up. The
      survey was sent to 192 centres which were part of the EORTC Lung Cancer Group.
      Thirty-eight centres from 12 different countries replied. Results showed that
      almost all the centres are doing very similar pretreatment evaluation procedures
      in stage III NSCLC. In the post-treatment follow-up setting, results were more
      varied in terms of frequency and type of scans used. The most commonly used test
      was a computed tomography (CT) of the chest and abdomen at 3 months post
      treatment. Positron emission tomography (PET)/CT and magnetic resonance imaging
      (MRI) of the brain with contrast were done only in symptomatic patients. This
      audit suggests that one CT scan at 3 months after the end of radical treatment
      has become a standard with little evidence showing it is better than a chest
      radiography (CXR). These data should be used to encourage research into molecular
      parameters or new imaging techniques that could be tested as more sensitive
      methods of picking up relapse in radically treated stage IIIA patients who has a
      high relapse rate in the first 12 months.

PMID- 22633749
TI  - Symptom clusters in a population-based ambulatory cancer cohort validated using
      bootstrap methods.
AB  - BACKGROUND: Cluster identification has emerged as a priority for symptom
      research. Variation in statistical approaches has hampered the identification of
      common clusters that should be targeted for intervention. The purpose of this
      study was to identify and validate common symptom clusters in a large population
      based cohort of ambulatory cancer subjects. METHODS: This descriptive, factor
      analysis study used bootstrap methods to derive a stable factor structure to
      identify symptom clusters in a population-based sample of cancer patients.
      Subjects were identified from a provincial symptom database and linked to other
      provincial databases. Symptom clusters were validated using confirmatory factor
      analysis in a randomly selected portion of the sample and model fit examined
      using common goodness of fit criteria. RESULTS: The cluster cohort included
      14,247 subjects. Three symptom clusters were identified: fatigue-sickness
      symptoms (tiredness, nausea, drowsiness and shortness of breath), emotional
      distress (depression and anxiety), and a poor sense of well-being (appetite and
      well-being). These clusters were stable across most sub-populations in the
      cohort. CONCLUSION: The identification of common symptom clusters using robust
      statistical methods will help to yield targets to improve symptom management and
      identify populations at risk for worse disease outcomes.

PMID- 22633747
TI  - Immunopathological patterns from EAE and Theiler's virus infection: Is multiple
      sclerosis a homogenous 1-stage or heterogenous 2-stage disease?
AB  - Multiple sclerosis (MS) is a disease which can presents in different clinical
      courses. The most common form of MS is the relapsing-remitting (RR) course, which
      in many cases evolves into secondary progressive (SP) disease. Autoimmune models
      such as experimental autoimmune encephalomyelitis (EAE) have been developed to
      represent the various clinical forms of MS. These models along with clinico
      pathological evidence obtained from MS patients have allowed us to propose '1
      stage' and '2-stage' disease theories to explain the transition in the clinical
      course of MS from RR to SP. Relapses in MS are associated with pro-inflammatory T
      helper (Th) 1/Th17 immune responses, while remissions are associated with anti
      inflammatory Th2/regulatory T (Treg) immune responses. Based on the '1-stage
      disease' theory, the transition from RR to SP disease occurs when the
      inflammatory immune response overwhelms the anti-inflammatory immune response.
      The '2-stage disease' theory proposes that the transition from RR to SP-MS occurs
      when the Th2 response or some other responses overwhelm the inflammatory response
      resulting in the sustained production of anti-myelin antibodies, which cause
      continuing demyelination, neurodegeneration, and axonal loss. The Theiler's virus
      model is also a 2-stage disease, where axonal degeneration precedes demyelination
      during the first stage, followed by inflammatory demyelination during the second
      stage.

PMID- 22633750
TI  - Phenotype heterogeneity of hyperbilirubinemia condition: the lesson by
      coinheritance of glucose-6-phosphate dehydrogenase deficiency and Crigler-Najjar
      syndrome type II in an Italian patient.

PMID- 22633751
TI  - Two isoforms of HOXA9 function differently but work synergistically in human MLL
      rearranged leukemia.
AB  - HOXA9 plays a critical role in both normal hematopoiesis and leukemogenesis,
      particularly in the development and maintenance of mixed lineage leukemia (MLL)
      rearranged leukemia. Through reverse transcription-polymerase chain reaction (RT
      PCR) analysis of HOXA9 transcripts in human leukemia and normal bone marrow
      samples, we identified a truncated isoform of HOXA9, namely HOXA9T, and found
      that both HOXA9T and canonical HOXA9 were highly expressed in leukemia cell lines
      bearing MLL rearrangements, relative to human normal bone marrow cells or other
      subtypes of leukemia cells. A frameshift in HOXA9T in exon I causes a premature
      stop codon upstream of the PBX-binding domain and the homeodomain, which leads to
      the generation of a non-homeodomain-containing protein. Unlike the canonical
      HOXA9, HOXA9T alone cannot transform normal bone marrow progenitor cells.
      Moreover, HOXA9T cannot cooperate with MEIS1 to transform cells, despite the
      presence of a MEIS1-binding domain. Remarkably, although the truncated isoforms
      of many proteins function as dominant-negative competitors or inhibitors of their
      full-length counterparts, this is not the case for HOXA9T; instead, HOXA9T
      synergized with HOXA9 in transforming mouse normal bone marrow progenitor cells
      through promoting self-renewal and proliferation of the cells. Collectively, our
      data indicate that both truncated and full-length forms of HOXA9 are highly
      expressed in human MLL-rearranged leukemia, and the truncated isoform of HOXA9
      might also play an oncogenic role by cooperating with canonical HOXA9 in cell
      transformation and leukemogenesis.

PMID- 22633752
TI  - Lissencephaly with marked ventricular dilation, agenesis of corpus callosum, and
      cerebellar hypoplasia caused by TUBA1A mutation.
AB  - We described the clinical course and pathological findings in a child with TUBA1A
      mutation. MRI revealed marked ventricular dilation with thin cortex, poorly
      differentiated basal ganglia, agenesis of corpus callosum, cerebellar hypoplasia
      with preserved vermis at 2 months of age. No gain of developmental milestones was
      observed until she died with respiratory failure at 23 months of age. A de novo
      missense mutation of c.1096G>A (G366R) was identified in TUBA1A gene.
      Pathological findings included a lack in lamination in the cerebral cortex,
      absent corpus callosum without Probst bundle, blurred demarcation among the
      striatum, internal capsule and globus pallidus in association with irregular
      running of myelinated fibers, cerebellar hypoplasia with irregular undulation in
      the dentate nucleus and inferior olivary nucleus, absent olfactory bulbs and
      tracts, and pyramidal tract hypoplasia. These findings are consistent with
      previous reports and will be a clue to diagnosis of TUBA1A mutation.

PMID- 22633753
TI  - Sustained expression and safety of human GNE in normal mice after gene transfer
      based on AAV8 systemic delivery.
AB  - GNE myopathy is an autosomal recessive adult onset disorder caused by mutations
      in the GNE gene. GNE encodes the bifunctional enzyme UDP-N-acetylglucosamine 2
      epimerase/N-acetyl mannosamine kinase, the key enzyme in the biosynthesis pathway
      of sialic acid. Additional functions for GNE have been described recently, but
      the mechanism leading from GNE mutation to this myopathy is unclear. Therefore a
      gene therapy approach could address all potential defects caused by GNE mutations
      in muscle. We show that AAV8 viral vectors carrying wild type human GNE cDNA are
      able to transduce murine muscle cells and human GNE myopathy-derived muscle cells
      in culture and to express the transgene in these cells. Furthermore, the
      intravenous administration of this viral vector to healthy mice allows expression
      of the GNE transgene mRNA and of the coexpressed luciferase protein, for at least
      6months in skeletal muscles, with no clinical or pathological signs of focal or
      general toxicity, neither from the virus particles nor from the wild type human
      GNE overexpression. Our results support the future use of an AAV8 based vector
      platform for a safe and efficient therapy of muscle in GNE myopathy.

PMID- 22633754
TI  - [New insights into perinatal hemochromatosis].
AB  - Perinatal hemochromatosis (PH) includes neonatal acute liver failure (ALF) with
      cirrhosis and extrahepatic iron overload sparing the reticuloendothelial system.
      This is the main cause of neonatal ALF. Prognosis is very poor, usually with
      neonatal death or neonatal orthotopic liver transplantation occurring in more
      than 70%. The recurrence rate is more than 90%. Diagnosis is hard to make and is
      proved after exclusion of other neonatal ALF causes. A recent physiopathological
      hypothesis proposed HP as a maternofetal alloimmune disease against the fetal
      liver. A maternal antibody may activate the terminal complement cascade,
      responsible for the membrane attack complex directed against fetal hepatocytes.
      Maternal prenatal treatment after a pregnancy complicated by PH modifies the
      course and the prognosis of this disease. In France, approval of prenatal IVIG
      treatment is required after analysis of clinical and pathological data by a
      national multidisciplinary committee.

PMID- 22633755
TI  - Workplace violence in emergency medicine: current knowledge and future
      directions.
AB  - BACKGROUND: Workplace violence (WPV) has increasingly become commonplace in the
      United States (US), and particularly in the health care setting. Assaults are the
      third leading cause of occupational injury-related deaths for all US workers.
      Among all health care settings, Emergency Departments (EDs) have been identified
      specifically as high-risk settings for WPV. OBJECTIVE: This article reviews
      recent epidemiology and research on ED WPV and prevention; discusses practical
      actions and resources that ED providers and management can utilize to reduce WPV
      in their ED; and identifies areas for future research. A list of resources for
      the prevention of WPV is also provided. DISCUSSION: ED staff faces substantially
      elevated risks of physical assaults compared to other health care settings. As
      with other forms of violence including elder abuse, child abuse, and domestic
      violence, WPV in the ED is a preventable public health problem that needs urgent
      and comprehensive attention. ED clinicians and ED leadership can: 1) obtain
      hospital commitment to reduce ED WPV; 2) obtain a work-site-specific analysis of
      their ED; 3) employ site-specific violence prevention interventions at the
      individual and institutional level; and 4) advocate for policies and programs
      that reduce risk for ED WPV. CONCLUSION: Violence against ED health care workers
      is a real problem with significant implications to the victims, patients, and
      departments/institutions. ED WPV needs to be addressed urgently by stakeholders
      through continued research on effective interventions specific to Emergency
      Medicine. Coordination, cooperation, and active commitment to the development of
      such interventions are critical.

PMID- 22633756
TI  - Improved auscultation skills in paramedic students using a modified stethoscope.
AB  - BACKGROUND: The Ventriloscope(r) (Lecat's SimplySim, Tallmadge, OH) is a modified
      stethoscope used as a simulation training device for auscultation. OBJECTIVE: To
      test the effectiveness of the Ventriloscope as a training device in teaching
      heart and lung auscultatory findings to paramedic students. METHODS: A
      prospective, single-hospital study conducted in a paramedic-teaching program. The
      standard teaching group learned heart and lung sounds via audiocassette
      recordings and lecture, whereas the intervention group utilized the modified
      stethoscope in conjunction with patient volunteers. Study subjects took a pre
      test, post-test, and a follow-up test to measure recognition of heart and lung
      sounds. RESULTS: The intervention group included 22 paramedic students and the
      standard group included 18 paramedic students. Pre-test scores did not differ
      using two-sample t-tests (standard group: t [16]=-1.63, p=0.12) and (intervention
      group: t [20]=-1.17, p=0.26). Improvement in pre-test to post-test scores was
      noted within each group (standard: t [17]=2.43, p=0.03; intervention: t
      [21]=4.81, p<0.0001). Follow-up scores for the standard group were not different
      from pre-test scores of 16.06 (t [17]=0.94, p=0.36). However, follow-up scores
      for the intervention group significantly improved from their respective pre-test
      score of 16.05 (t [21]=2.63, p=0.02). CONCLUSION: Simulation training using a
      modified stethoscope in conjunction with standardized patients allows for
      realistic learning of heart and lung sounds. This technique of simulation
      training achieved proficiency and better retention of heart and lung sounds in a
      safe teaching environment.

PMID- 22633757
TI  - Adult colonic intussusception mimicking renal colic.

PMID- 22633758
TI  - Application of the FIA score to German rescue helicopter accidents to predict
      fatalities in Helicopter Emergency Medical Systems (HEMS) crashes.
AB  - BACKGROUND: In the past several decades, multiple studies have examined factors
      influencing occupant survival in aviation crashes, but only a few have addressed
      this question in Helicopter Emergency Medical Systems (HEMS) accidents. The four
      point FIA Score is a valid tool to measure fatality risk in aviation crashes.
      OBJECTIVE: The aim of the present study was to analyze the performance of the FIA
      Score when applied to German HEMS accidents, and to determine the prognostic
      value for fatalities and for survival. METHODS: The FIA Score uses three
      parameters (F=fire; I=Instrument meteorological conditions; A=Away from airport)
      to determine the fatality risk after crashes. Data for German HEMS accidents
      between October 1970 and December 2009 were gathered retrospectively from the
      Federal Agency for Flight Accident Investigation. Accidents were graded according
      to the FIA Score by two emergency physician-pilots, and crash fatality rates
      (CFR) were calculated. RESULTS: A total of 99 HEMS accidents were analyzed that
      occurred from September 1970 to December 2009. In 19.2% of these, at least one
      occupant was fatally injured. There were 63 accidents (63.6%) that took place
      with no injuries; 8 occurred with minor injuries (8.1%); and 9 resulted in major
      injuries (9.1%). A total of 72 data sets were complete and were used for
      analysis. Depending on the FIA Score (FIA0, FIA1, FIA2, and FIA3), CFRs of 0.0%,
      8.1%, 53.3%, and 100.0%, respectively, were calculated. CONCLUSIONS: The FIA
      Score is a valuable tool in German HEMS accident analysis. It can predict
      fatalities and is easy to use. Thus, it may also be a valuable tool in EMS call
      centers to predict survival after a crash.

PMID- 22633759
TI  - Myocardial ischemia associated with clenbuterol abuse: report of two cases.
AB  - BACKGROUND: Clenbuterol is an orally administered long-acting beta-2 adrenergic
      agonist closely related to albuterol that, in recent years, has become a
      substance of abuse in the bodybuilding and athletic community. OBJECTIVES: We
      report two cases of acute myocardial ischemia associated with clenbuterol abuse
      in two healthy young male body builders. CASE REPORT: Two male bodybuilders, ages
      18 and 22 years, presented to the Emergency Department with palpitations, nausea,
      vomiting, chest pain, diaphoresis, and tachycardia shortly after ingesting
      clenbuterol. Both patients experienced prolonged sinus tachycardia that, in one
      patient, was relatively resistant to both beta- and calcium channel blockade.
      Both patients were found to have elevated troponin levels, the first patient as
      high as 4.71 ng/mL (normal<0.04 ng/mL). Further investigation revealed normal
      coronary arteries at catheterization and normal cardiac magnetic resonance
      imaging in the first patient, and normal echocardiograms for both patients. The
      tachycardia gradually resolved and both patients recovered uneventfully. The
      etiology of cardiac ischemia in these patients is uncertain. CONCLUSIONS:
      Emergency physicians should be aware of the clinical presentation of clenbuterol
      abuse and overdose, and the possibility of related cardiac ischemia and rhythm
      disturbances. Suggested treatment includes intravenous fluids, oxygen, aspirin,
      beta-blockers, and benzodiazepines, although efficacy remains unproven.

PMID- 22633761
TI  - External iliac artery rupture presenting with lumbar herniated disc.

PMID- 22633760
TI  - Prospective evaluation of daily performance metrics to reduce emergency
      department length of stay for surgical consults.
AB  - BACKGROUND: As part of a quality improvement initiative to reduce Emergency
      Department (ED) length of stay (LOS) for surgical consult patients, we e-mailed
      performance metrics to key stakeholders on a daily basis. ED and Surgery
      leadership used these daily metrics to identify and remedy contributing factors
      for increased ED LOS in patients who received surgical consults. OBJECTIVE: To
      evaluate whether a quality improvement process driven by a daily performance
      metric e-mail would be associated with a change in ED LOS for surgical consult
      patients. METHODS: Prospective before-after study looking at ED LOS for surgical
      consult patients after an e-mail intervention at a tertiary academic teaching
      hospital. All consecutive adult ED patients between July 1, 2010 and October 1,
      2010 who received a general surgical consult were enrolled. The primary outcome
      measure was ED LOS, and secondary outcome measure was time to consultation.
      RESULTS: There were 916 patients who had surgical consults placed during the
      study period; 459 patients presented before the intervention and 457 patients
      presented after the intervention. The median LOS decreased 54 min, from 463 min
      (interquartile range [IQR] 326-617) before the intervention to 409 min (IQR 294.5
      528.5) after the intervention (p < 0.001). Time to consultation decreased 25 min,
      from a median of 160 min (IQR 87-265) to 135 min (IQR 70-239.5) (p = 0.002).
      There was no difference in age, severity, number of consults, or disposition.
      There was also no difference in median LOS for other consultation services or in
      previous years during the same time period. CONCLUSIONS: ED LOS and time to
      consultation were decreased for surgical consult patients after initiation of
      daily performance metric e-mails.

PMID- 22633762
TI  - Anaplastic large cell lymphoma as a cause of rapidly appearing subcutaneous
      nodules in an HIV-infected patient.

PMID- 22633763
TI  - Multidrug-resistant tuberculous spondylitis.

PMID- 22633765
TI  - A new era of hepatitis C treatment.

PMID- 22633764
TI  - [Consensus document of Gesida and Spanish Secretariat for the National Plan on
      AIDS (SPNS) regarding combined antiretroviral treatment in adults infected by the
      human immunodeficiency virus (January 2012)].
AB  - This consensus document has been prepared by a panel consisting of members of the
      AIDS Study Group (Gesida) and the Spanish Secretariat for the National Plan on
      AIDS (SPNS) after reviewing the efficacy and safety results of clinical trials,
      cohort and pharmacokinetic studies published in medical journals, or presented in
      medical scientific meetings. Gesida has prepared an objective and structured
      method to prioritise combined antiretroviral treatment (cART) in naive patients.
      Recommendations strength (A, B, C) and the evidence which supports them (I, II,
      III) are based on a modification of the Infectious Diseases Society of America
      criteria. The current antiretroviral treatment (ART) of choice for chronic HIV
      infection is the combination of three drugs. ART is recommended in patients with
      symptomatic HIV infection, in pregnancy, in serodiscordant couples with high
      transmission risk, hepatitis B fulfilling treatment criteria, and HIV
      nephropathy. Guidelines on ART treatment in patients with concurrent diagnosis of
      HIV infection and an opportunistic type C infection are included. In asymptomatic
      patients ART is recommended on the basis of CD4 lymphocyte counts, plasma viral
      load and patient co-morbidities, as follows: 1) therapy should be started in
      patients with CD4 counts <350 cells/MUL; 2) when CD4 counts are between 350 and
      500 cells/MUL, therapy will be recommended and only delayed if patient is
      reluctant to take it, the CD4 are stabilised, and the plasma viral load is low;
      3) therapy could be deferred when CD4 counts are above 500 cells/MUL, but should
      be considered in cases of cirrhosis, chronic hepatitis C, high cardiovascular
      risk, plasma viral load >10(5) copies/mL, proportion of CD4 cells <14%, and in
      people aged >55 years. ART should include 2 reverse transcriptase inhibitors
      nucleoside analogues and a third drug (non-analogue reverse transcriptase
      inhibitor, ritonavir boosted protease inhibitor or integrase inhibitor). The
      panel has consensually selected and given priority to using the Gesida score for
      some drug combinations, some of them co-formulated. The objective of ART is to
      achieve an undetectable viral load. Adherence to therapy plays an essential role
      in maintaining antiviral response. Therapeutic options are limited after ART
      failures, but an undetectable viral load may be possible nowadays. Adverse events
      are a fading problem of ART. Guidelines in acute HIV infection, in women, in
      pregnancy, and to prevent mother-to-child transmission and pre- and post
      exposition prophylaxis are commented upon. Management of hepatitis B or C co
      infection, other co-morbidities, and the characteristics of ART in HIV-2
      infection are included.

PMID- 22633767
TI  - Is there a consensus about eosinophilic esophagitis?

PMID- 22633768
TI  - Turning classical bile acid physiology into everyday pharmacology: impact of a
      bile acid transporter inhibitor on chronic constipation.

PMID- 22633770
TI  - Hyperammonemic encephalopathy in diffuse liver metastasis: is this the end stage?

PMID- 22633771
TI  - Endoscopic vs surgical resection for Barrett's intramucosal adenocarcinoma:
      beyond a therapeutic equipoise.

PMID- 22633772
TI  - An unusual cause of lower GI bleeding.

PMID- 22633773
TI  - An unusual cause of abdominal pain and fever.

PMID- 22633775
TI  - Bilaterally swollen and painless submandibular glands: do they matter to
      gastroenterologists?

PMID- 22633777
TI  - On the emergence of grammatical language as a means of bypassing the limitations
      of working memory capacity: Comment on "Interaction between lexical and
      grammatical language systems in the brain" by Alfredo Ardila.

PMID- 22633776
TI  - The quadratic hazard model for analyzing longitudinal data on aging, health, and
      the life span.
AB  - A better understanding of processes and mechanisms linking human aging with
      changes in health status and survival requires methods capable of analyzing new
      data that take into account knowledge about these processes accumulated in the
      field. In this paper, we describe an approach to analyses of longitudinal data
      based on the use of stochastic process models of human aging, health, and
      longevity which allows for incorporating state of the art advances in aging
      research into the model structure. In particular, the model incorporates the
      notions of resistance to stresses, adaptive capacity, and "optimal" (normal)
      physiological states. To capture the effects of exposure to persistent external
      disturbances, the notions of allostatic adaptation and allostatic load are
      introduced. These notions facilitate the description and explanation of
      deviations of individuals' physiological indices from their normal states, which
      increase the chances of disease development and death. The model provides a
      convenient conceptual framework for comprehensive systemic analyses of aging
      related changes in humans using longitudinal data and linking these changes with
      genotyping profiles, morbidity, and mortality risks. The model is used for
      developing new statistical methods for analyzing longitudinal data on aging,
      health, and longevity.

PMID- 22633780
TI  - Preanalytic conditions of the C-reactive protein are of paramount importance to
      use as a predictor of cardiovascular disease in clinical practice.

PMID- 22633778
TI  - Does vascular endothelial growth factor participate in uterine myoma growth
      stimulation?
AB  - OBJECTIVE: Peptide growth factors play a role in the rebuilding of extracellular
      matrix in the course of leiomyoma growth, and exert a regulative effect on the
      cell only when they bind with a specific membrane receptor and transmit a signal
      into the cell. A high content of certain peptide growth factors and their
      receptors in leiomyoma suggests that in the course of the tumour growth
      hyperstimulation of cells takes place. A combined action of various peptide
      growth factors causes an amplification of signal paths in cells, inducing gene
      expression of proteins responsible for cell division and changes of metabolism.
      We therefore decided to evaluate the amounts and expression of VEGF, their
      receptor and mRNA levels. STUDY DESIGN: Studies were performed on human
      myometrium and uterine leiomyomas of various weights (small: i.e. less than 10 g,
      and large: i.e. more than 100 g). Expression and content of VEGF-A, D and VEGF R
      1, R-2 were analysed with Western blot and ELISA methods, respectively. The RT
      PCR method was used to determine VEGF mRNA levels. RESULTS: Our immunoblotting
      studies and immunoenzymatic assay, as well as RT-PCR technique, did not detect
      significant differences in the expression of VEGFs and their receptors in control
      myometrium and in uterine leiomyomas. CONCLUSION: The increase in the amount of
      some peptide growth factors, especially FGFs and IGF-I, in large leiomyomas
      without any change in VEGF content means a decrease in the proportional
      relationship of the latter to other growth factors. Stimulation of extracellular
      matrix formation seems stronger than angiogenesis during myoma growth.

PMID- 22633779
TI  - Prognostic significance of elevated lipoprotein(a) in coronary artery
      revascularization patients.
AB  - BACKGROUND: Although lipoprotein(a) [Lp(a)] has been considered a cardiovascular
      risk factor for many years, there is a paucity of data in regard to the potential
      risk of elevated Lp(a) in symptomatic patients with CAD. Therefore, we sought to
      evaluate whether elevated Lp(a) is associated with worse outcome in symptomatic
      patients with coronary artery disease (CAD), and to clarify the prognostic value
      of Lp(a) in the era of coronary artery revascularization. METHODS: 6252
      consecutive subjects (59.2% male, mean age 61.2 +/- 11.2 years) suspected of
      having CAD underwent coronary angiography. Laboratory values for lipid parameters
      including Lp(a) were obtained on the day of coronary angiography. Baseline risk
      factors, coronary angiographic findings, length of follow-up, and major adverse
      cardiovascular events (MACE), including cardiac death and non-fatal myocardial
      infarction were recorded. RESULTS: Over a mean follow-up period of 3.1 +/- 2.2
      years, there were 100 MACE (56 cardiac deaths and 44 non-fatal myocardial
      infarctions), with an event rate of 1.6%. In multivariate Cox regression
      analysis, elevated Lp(a) was a significant predictor of MACE [hazard ratio 1.773
      (95% confidence interval 1.194-2.634, p=0.005)], and the addition of this factor
      to the model significantly increased the global x(2) value over traditional risk
      factors and CAD (from 79.1 to 88.7, p=0.003). CONCLUSIONS: Elevated Lp(a) is an
      independent prognostic risk factor for cardiovascular events, and moreover, has
      incremental prognostic value in symptomatic patients with coronary artery
      revascularization.

PMID- 22633781
TI  - Simultaneous gains tuning in boiler/turbine PID-based controller clusters using
      iterative feedback tuning methodology.
AB  - Tuning a complex multi-loop PID based control system requires considerable
      experience. In today's power industry the number of available qualified tuners is
      dwindling and there is a great need for better tuning tools to maintain and
      improve the performance of complex multivariable processes. Multi-loop PID tuning
      is the procedure for the online tuning of a cluster of PID controllers operating
      in a closed loop with a multivariable process. This paper presents the first
      application of the simultaneous tuning technique to the multi-input-multi-output
      (MIMO) PID based nonlinear controller in the power plant control context, with
      the closed-loop system consisting of a MIMO nonlinear boiler/turbine model and a
      nonlinear cluster of six PID-type controllers. Although simplified, the dynamics
      and cross-coupling of the process and the PID cluster are similar to those used
      in a real power plant. The particular technique selected, iterative feedback
      tuning (IFT), utilizes the linearized version of the PID cluster for signal
      conditioning, but the data collection and tuning is carried out on the full
      nonlinear closed-loop system. Based on the figure of merit for the control system
      performance, the IFT is shown to deliver performance favorably comparable to that
      attained through the empirical tuning carried out by an experienced control
      engineer.

PMID- 22633782
TI  - Nursing workforce a global priority area for health policy and health services
      research: a special issue.

PMID- 22633783
TI  - The effect of cysteamine bitartrate on adiponectin multimerization in non
      alcoholic fatty liver disease and healthy subjects.
AB  - OBJECTIVE: To determine the effects of cysteamine on adiponectin multimerization
      in sera of patients with nonalcoholic fatty liver disease (NAFLD). STUDY DESIGN:
      Sera from 10 children with biopsy-proven NAFLD treated with cysteamine were
      assayed for adiponectin multimers at baseline, after 24 weeks of treatment, and
      again 16 weeks after discontinuing treatment. Pretreatment sera from subjects
      with NAFLD and from adult controls without NAFLD controls (n = 8) were incubated
      in cysteamine and multimers were measured 1 hour later. A cysteamine/adiponectin
      multimer dose-response curve was created. RESULTS: Following 24 weeks of
      cysteamine therapy, the mean percentage increase for high, medium (MMW), and low
      (LMW) molecular weight multimers and total adiponectin from baseline was 53% (P =
      .02), 19% (P = .02), 29.4% (P = .03), and 49.3% (P = .05), respectively. Levels
      returned to baseline at 16 weeks after stopping therapy, unlike hepatic
      transaminase levels which remained low. Sera from 0 week, incubated in cysteamine
      for 1 hour, showed a significant mean percent increase in LMW adiponectin levels
      and a mean percent reduction in MMW levels compared with baseline in adults with
      and without NAFLD. CONCLUSIONS: Cysteamine impacts adiponectin multimerization.
      Long-term cysteamine therapy increases levels of all multimers, whereas, in vitro
      short-term exposure causes a rapid increase in LMW and reduction in MMW multimers
      in NAFLD and healthy controls. Cysteamine may be a potential therapeutic agent
      for conditions associated with insulin-resistance, oxidative stress, and
      depressed adiponectin levels.

PMID- 22633785
TI  - The use of the mobile voice laboratory in the operating room during type I
      thyroplasty with Gore-Tex((r)).
AB  - INTRODUCTION AND OBJECTIVE: The purposes of this study are to demonstrate the use
      of the mobile voice lab in type I thyroplasty with Gore-Tex((r)) using analysis
      of spectrogram and fundamental frequency in the operating room, and also to show
      how to do this procedure. METHODS: Voice samples were recorded in the operating
      room immediately before and during type I thyroplasty. Six-week postoperative
      samples were also taken in the voice laboratory. Fundamental frequency and
      spectral analysis were analyzed. Spectrograms were evaluated by blind panel of 4
      judges on a 100mm visual analogue scale. All three time points were compared and
      statistical analysis performed. Pre and postoperative V-RQOL scores were also
      compared. RESULTS: Significant improvement in spectrogram ratings were seen
      between before and during (P<.001), and before and after voice samples (P<.017).
      There was no significant difference between during and after scores, suggesting
      the persistence of the intraoperative improvement in this measure. Changes in
      fundamental frequency were not statistically significant, although fundamental
      frequency tended to increase in women and decrease in men after type I
      thyroplasty. Mean V-RQOL scores improved from 48.08 a 85.08 (P<.001).
      CONCLUSIONS: The mobile voice laboratory may be useful during type I thyroplasty
      with Gore-Tex((r)). It offers an opportunity for the surgeon and voice
      pathologist to continue to collaborate in the treatment of patients with
      unilateral vocal fold paralysis.

PMID- 22633786
TI  - Reappraisal of photodynamic therapy as first-line therapy in management of oral
      pre-malignant lesions.

PMID- 22633787
TI  - Refraction-compensated motion tracking of unrestrained small animals in positron
      emission tomography.
AB  - Motion-compensated radiotracer imaging of fully conscious rodents represents an
      important paradigm shift for preclinical investigations. In such studies, if
      motion tracking is performed through a transparent enclosure containing the awake
      animal, light refraction at the interface will introduce errors in stereo pose
      estimation. We have performed a thorough investigation of how this impacts the
      accuracy of pose estimates and the resulting motion correction, and developed an
      efficient method to predict and correct for refraction-based error. The
      refraction model underlying this study was validated using a state-of-the-art
      motion tracking system. Refraction-based error was shown to be dependent on
      tracking marker size, working distance, and interface thickness and tilt.
      Correcting for refraction error improved the spatial resolution and quantitative
      accuracy of motion-corrected positron emission tomography images. Since the
      methods are general, they may also be useful in other contexts where data are
      corrupted by refraction effects.

PMID- 22633790
TI  - Missed opportunities for recognition of ischemic stroke in the emergency
      department.
AB  - INTRODUCTION: Evidence suggests that a significant number of patients discharged
      from the hospital with a diagnosis of ischemic stroke are not identified as
      having a stroke on admission. Those presenting with "nontraditional" stroke
      symptoms may be less likely to be diagnosed correctly. We aimed to establish
      whether there was an association between symptom presentation and diagnostic
      accuracy and to identify the type and frequency of nontraditional symptoms that
      resulted in a missed diagnosis in the emergency department. METHODS: We reviewed
      the medical records of 189 patients discharged with a diagnosis of ischemic
      stroke from Yale-New Haven Hospital. We performed chi(2) analysis to determine
      whether an association existed between symptom presentation and diagnostic
      accuracy. Descriptive statistics allowed us to identify symptom type and
      frequency in patients with a missed diagnosis. RESULTS: A diagnosis of suspected
      stroke was missed in 15.3% of patients who presented to the emergency department.
      We found a strong association (P < 0.0001) between symptom presentation and
      diagnostic accuracy. Of the patients presenting with any "traditional" symptom,
      4% were missed. Of those presenting with only nontraditional symptoms, 64% were
      missed (odds ratio, 43.4; 95% confidence interval, 15.0-125.4). Nontraditional
      symptoms included generalized weakness, altered mental status, altered gait, and
      dizziness. DISCUSSION: In order to facilitate appropriate management of patients
      with ischemic stroke, emergency nurses must be aware that symptom presentation is
      highly variable. Patients presenting with nontraditional symptoms may benefit
      from an immediate and comprehensive neurological evaluation.

PMID- 22633791
TI  - Eating rate is associated with cardiometabolic risk factors in Korean adults.
AB  - BACKGROUND AND AIM: Eating slowly is a crucial concept in behavioural nutrition
      and is recommended for weight management as it is believed to have an important
      effect on satiety control. This study aimed to determine whether or not eating
      rate is associated with cardiometabolic risk factors. METHODS AND RESULTS: This
      was a cross-sectional study involving 8775 Korean adults, who visited the Center
      for Health Promotion of Korea University Anam Hospital in Seoul, Korea. In male
      study participants, weight and body mass index (BMI) were found to depend on
      eating rate after adjusting for age, alcohol consumption, smoking, exercise and
      total energy intake. When adjusted for age, alcohol consumption, smoking,
      exercise and BMI, differences were found between the eating rate groups with
      respect to high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase
      (ALT) and alkaline phosphatase (ALP) values, white blood cell (WBC) count and
      total energy intake. Female participants were found to be different from males in
      that diastolic blood pressure and low-density lipoprotein (LDL)- and HDL
      cholesterol values were significantly different between each eating rate group,
      while ALT and ALP values, WBC count and total energy intake were not. Compared
      with the slow eating rate group (>15 min), the fastest eating rate group (<5 min)
      had significantly increased odds ratios for cardiometabolic risk factors such as
      high glucose and low HDL-cholesterol levels in males, even after adjusting for
      BMI. CONCLUSION: Fast eating rates are associated with obesity and other
      cardiometabolic risk factors, particularly in men. Thus, eating slowly is
      recommended for weight reduction and to decrease cardiovascular risk factors.

PMID- 22633792
TI  - Heritability, genetic correlation and linkage to the 9p21.3 region of mixed
      platelet-leukocyte conjugates in families with and without early myocardial
      infarction.
AB  - BACKGROUND AND AIMS: Variations in mixed platelet-leukocyte conjugate formation
      in human whole blood could be genetically determined. We quantified platelet and
      leukocyte activation and interaction in families with or without early myocardial
      infarction and evaluated their heritability, genetic correlation and linkage to
      the 9p21.3 region. METHODS AND RESULTS: The study population included 739
      subjects (>= 15 years old) from 54 large pedigrees, 23 with and 31 without
      familial myocardial infarction. Mixed platelet-leukocyte conjugates and markers
      of platelet or leukocyte activation (P-selectin, CD11b and L-selectin surface
      expression) were measured both before and after in vitro blood stimulation with
      collagen-ADP. All traits had significant genetic components (17.5-65.3% of the
      phenotypic variability), while shared household effects (0-39.6%) and
      environmental covariates (0-10.2%) tended to be smaller. Stimulated platelet
      polymorphonuclear leukocyte (PMN) and platelet-monocyte conjugates showed the
      highest linkage to the 9p21.3 region (LOD = 0.94 and 1.33, respectively;
      empirical p value = 0.017 and 0.009). PMN markers resulted strongly genetically
      correlated between them in bivariate analysis among pairs of quantitative traits.
      CONCLUSION: This study supports a genetic regulation of human mixed platelet
      leukocyte conjugates.

PMID- 22633793
TI  - Adherence to Mediterranean diet reduces the risk of metabolic syndrome: a 6-year
      prospective study.
AB  - BACKGROUND AND AIMS: Benefits of Mediterranean diet on MetS risk have been
      suggested, but overall prospective evidence in the general population is limited.
      For the first time, the prospective association of adherence to Mediterranean
      diet with the 6-y risk of MetS and its components was evaluated in a large cohort
      in Europe. METHODS AND RESULTS: Subjects included were participants from the
      Supplementation en Vitamines et Mineraux AntioXydants (SU.VI.MAX) study.
      Adherence to Mediterranean diet was assessed using traditional Mediterranean diet
      score (MDS), an updated Mediterranean score (MED) and Mediterranean style-dietary
      pattern score (MSDPS) calculated from at least three 24-h records. In 3232
      subjects, the association between Mediterranean diet scores and 6-y risk of MetS
      was evaluated. The association between Mediterranean scores and MetS components
      was also estimated. A lower risk of MetS was observed with increasing MED score
      (P-trend = 0.001) and MDS (P-trend = 0.03) in multivariate models. The adjusted
      odds ratios (95% Confidence Interval) for MetS risk were 0.47 (0.32-0.69) and
      0.50 (0.32-0.77) in subjects in the highest versus lowest tertile of MED score
      and MDS, respectively. The MED score was inversely associated with waist
      circumference, systolic blood pressure and triglycerides, and directly associated
      with HDL-cholesterol. The MDS was negatively associated with waist circumference
      and triglycerides, and MSDPS was positively associated with HDL-cholesterol.
      CONCLUSIONS: All Mediterranean diet scores were associated in a potentially
      beneficial direction with components of MetS or MetS incidence. Our findings
      support that individuals should be encouraged to follow a Mediterranean dietary
      pattern for reduction of MetS risk.

PMID- 22633794
TI  - Exercise as a new physiological stimulus for brown adipose tissue activity.
AB  - BACKGROUND AND AIM: Brown adipose tissue (BAT) plays a major role in body energy
      expenditure counteracting obesity and obesity-associated morbidities. BAT
      activity is sustained by the sympathetic nervous system (SNS). Since a massive
      activation of the SNS was described during physical activity, we investigated the
      effect of endurance running training on BAT of young rats to clarify the role of
      exercise training on the activity and recruitment state of brown cells. METHODS
      AND RESULTS: Male, 10-week-old Sprague Dawley rats were trained on a motor
      treadmill (approximately 60% of VO2max), 5 days/week, both for 1 and 6 weeks. The
      effect of endurance training was valuated using morphological and molecular
      approaches. Running training affected on the morphology, sympathetic tone and
      vascularization of BAT, independently of the duration of the stimulus.
      Functionally, the weak increase in the thermogenesis (no difference in UCP-1),
      the increased expression of PGC-1alpha and the membrane localization of MCT-1
      suggest a new function of BAT. Visceral fat increased the expression of the
      FOXC2, 48 h after last training session and some clusters of UCP-1 paucilocular
      and multilocular adipocytes appeared. CONCLUSION: Exercise seemed a weakly
      effective stimulus for BAT thermogenesis, but surprisingly, without the supposed
      metabolically hypoactive effects. The observed browning of the visceral fat, by a
      supposed white-to-brown transdifferentiation phenomena suggested that exercise
      could be a new physiological stimulus to counteract obesity by an adrenergic
      regulated brown recruitment of adipocytes.

PMID- 22633795
TI  - Cardiometabolic risk reduction in an intensive cardiovascular health program.
AB  - BACKGROUND AND AIMS: Insulin and leptin are important markers of insulin
      resistance and vascular inflammation in metabolic and cardiovascular diseases.
      This study evaluated changes in circulating levels of insulin and leptin during a
      cardiovascular health program to improve our understanding of cardiometabolic
      risk reduction. METHODS AND RESULTS: Participants (n=76) completed a prospective,
      nonrandomized program designed to stabilize or reverse progression of coronary
      artery disease through dietary changes, exercise, stress management, and group
      support. Controls (n=76) were matched to participants based on age, gender, and
      disease status. Traditional cardiovascular risk factors were assessed at
      baseline, 12 weeks, and 52 weeks by standard methods. Dietary data were collected
      by 72-h recall and evaluated by Food Processor(r) v8.4.0. Ultrasensitive insulin
      and leptin levels were measured by radioimmunoassay. Participants successfully
      reduced their total caloric intake from >2000 calories per day to ~ 1700 calories
      per day (p<0.05 compared to controls), lowered daily fat intake by >60% (p<0.001
      compared to controls), and increased carbohydrate intake by >30% (p<0.001).
      Repeated-measures ANOVA indicated significant beneficial changes (p<0.001
      compared to controls) in plasma insulin (-19%) and leptin (-33%) during the
      lifestyle program, as well as improvement in traditional cardiovascular risk
      factors. Response was similar between men and women for most risk factors and was
      not markedly influenced by medication use. CONCLUSION: Lifestyle changes focusing
      on diet, physical activity, and stress reduction can successfully modify both
      cardiovascular and metabolic risk factors, with the potential to mediate
      cardiometabolic risk through beneficial anti-inflammatory and anti-oxidative
      effects on the vasculature.

PMID- 22633796
TI  - Impact of body mass index and waist circumference on the cardiovascular risk and
      all-cause death in a general population: data from the PAMELA study.
AB  - BACKGROUND AND AIMS: Elevated values of body mass index (BMI) and waist
      circumference (WC) are associated with an augmented cardiovascular (CV) risk. It
      is debated, however, whether and to what extent this depends on the body fat
      increase 'per se' or on the related cardiometabolic alterations. METHODS AND
      RESULTS: In 2005 subjects randomly selected from the general population of Monza
      (Italy), we assessed BMI, WC, office, home and 24 h blood pressure (BP), heart
      rate and metabolic variables. The impact of BMI and WC on the incidence of CV
      events, CV and all-cause mortality was estimated during a 148-month follow-up.
      Progressively higher values of BMI and WC were associated with a progressive
      increase in office, home and 24 h BP and in erratic BP variability (P < 0.0001
      for trend). Metabolic variables were directly and significantly (P < 0.0001)
      related to BMI and WC, while an inverse significant relationship was detected
      with high-density lipoprotein (HDL)-cholesterol. The incidence of CV events, CV
      and all-cause deaths increased progressively from the lowest to the highest
      quintile of BMI and WC (P for trend always <0.005). Baseline BMI and WC higher by
      respectively 1 kg m-2 and 1 cm were associated with an increased risk of CV
      events, CV and all-cause death by 8%, 12% and 7% (for baseline BMI) and 4%, 5%
      and 4% (for baseline WC), respectively. After adjustment for confounders, only
      the increased risk of CV death related to higher baseline BMI remained
      significant (hazard ratio (HR) 1.062, confidence interval (CI) 95% 1.003-1.126, P
      < 0.05). CONCLUSION: The adverse prognostic impact of the accumulation of body
      fat is mediated by the associated haemodynamic and metabolic alterations.
      Baseline values of BMI, however, are an independent predictor of CV mortality.

PMID- 22633797
TI  - HbA1c levels and all-cause mortality in type 2 diabetic patients: epidemiological
      evidence of the need for personalised therapeutic targets.
AB  - BACKGROUND AND AIM: The aim of the present case-control study is to explore the
      effect of case mix on the relationship between glycated haemoglobin (HbA1c) and
      mortality in type 2 diabetic patients. METHODS AND RESULTS: A nested case-control
      study data set was generated from the cohort-study data set (n = 4140 type 2
      diabetic outpatients) by sampling controls from the risk sets. Cases (n = 427)
      were compared with an equal number of controls chosen from those members of the
      cohort who were at risk for the same follow-up time of the case, matched for age
      (+/-3 years), sex, body mass index (BMI) (+/-2 kg m(-2)), duration of diabetes
      (+/-5 years), and Charlson's Comorbidity Score (CCS) (+/-1). The main predefined
      analysis was the comparison of cases and controls for proportion of patients with
      each HbA1c class (<6.5%, 6.5-7.4%, 7.5-8.4% and >=8.5%). During a mean follow-up
      of 5.7 +/- 3.5 years, 427 deaths were recorded. The lowest risk of death was
      observed in the HbA1c 6.5-7.4% category; a lower HbA1c was associated with a non
      significant trend towards a higher risk. The risk associated with a low (<6.5%)
      HbA1c was significantly greater in patients who were insulin-treated than in the
      rest of the sample. CONCLUSIONS: The present study suggests that glycaemic
      targets should be individualised on the basis of the characteristics of each
      patient, considering age, co-morbidity and duration of diabetes. Caution should
      be used in prescribing insulin to reach near-normoglycaemia, particularly in
      older, frail patients.

PMID- 22633798
TI  - Influence of flow direction and flow rate on the initial adhesion of seven
      Listeria monocytogenes strains to fine polished stainless steel.
AB  - The effects of flow direction and shear stress on the adhesion of different
      strains of Listeria monocytogenes to fine polished stainless steel under liquid
      flow conditions were investigated. Furthermore, the relationship between cell
      surface properties and cell size and the initial adhesion rate (IAR) was studied.
      A method, including fluorescence microscopy and a flow perfusion system, was
      developed and used to examine the real-time initial cell adhesion of different L.
      monocytogenes species in situ to opaque surfaces under flow conditions. The
      results demonstrated that shear stress was the determining factor for the initial
      adhesion of L. monocytogenes under flow conditions. The flow direction in
      relation to the orientation of surface features (the scratches) could be
      disregarded. IARs were dependent on the shear stress and strain type. The strain
      EGDe, which had the lowest IAR, had the largest cell size, was the least
      hydrophobic and possessed the most electron-donating cell surface. Except for the
      L. monocytogenes strain EGDe, no clear correlations were found between the IAR
      and cell surface properties, or cell size. In conclusion, many factors may be
      involved in determining the initial adhesion of L. monocytogenes to stainless
      steel under flow conditions. Two of the main factors are flow rate/shear stress
      and strain specificity.

PMID- 22633799
TI  - Duplex RT-qPCR for the detection of hepatitis E virus in water, using a process
      control.
AB  - Human hepatitis E virus (HEV) causes acute hepatitis in humans, predominantly by
      contamination of food and water. HEV, in particular genotype III, is currently
      considered to be an emerging pathogen in industrialized countries. Because of the
      low infectious dose, an efficient and rapid virus concentration method is
      required to detect low amounts of HEV in food and water samples for routine
      control. Because of the absence of a reliable cell culture method for the main
      enteric viruses most involved in the outbreaks, reverse transcription
      quantitative real time PCR (RT-qPCR) is now widely used for the detection of RNA
      viruses in food and water samples. One of the general requirements for viral
      diagnosis concerns the use of a process control to monitor the efficiency of the
      concentration of viral particles, the extraction of nucleic acid and the presence
      of the potential inhibitors of the RT-qPCR reaction. The aim of this study was to
      provide a rapid and sensitive method for detecting HEV in water. The method is
      based on viral concentration by filtration on membrane filters and direct lysis
      of adsorbed viruses from filters before RNA extraction and RT-qPCR amplification.
      We developed a one-step duplex RT-qPCR for detecting HEV and the murine norovirus
      (MNV-1) was used as a process control. The data show that MNV-1 offers a very
      reliable and simple way of monitoring false-negative results and is a valuable
      tool in the routine diagnostic laboratory. The limit of detection (LOD) was in
      the range of 700 to 3500 HEV genome copies/0.5L bottled water and 3500 HEV genome
      copies/0.5L tap water.

PMID- 22633800
TI  - Heat resistance of Listeria monocytogenes in semi-skim milk supplemented with
      vanillin.
AB  - The kinetics of destruction of Listeria monocytogenes Scott A in semi-skim milk
      heated at 55, 58, 60 and 62 degrees C without and with addition of 900, 1400 and
      1800 ppm of vanillin was studied. Survival curves displayed an initial shoulder
      phase followed by an accelerating killing phase. Addition of vanillin to semi
      skim milk heated between 55 and 62 degrees C reduced the heat resistance of L.
      monocytogenes, effect that was more evident at the lowest temperatures. Two
      kinetic inactivation models were used to fit the data: the shoulder+log-linear
      model and the Weibull model. The presence of vanillin increased the death rate
      and reduced the shoulder length of L. monocytogenes in milk when working at low
      temperatures, while at the highest temperatures, this effect was less evident.
      Weibull model also showed that at lower temperatures 55 degrees C-58 degrees C,
      the population was inactivated at different treatment times, leaving a larger
      proportion of resistant microorganisms. Increasing the heating temperature to 60
      degrees C and 62 degrees C, the biggest proportion of the population was
      destroyed in a very short time, while a very little proportion with higher
      resistance remained viable. Results suggest that the use of subinhibitory
      concentrations of vanillin added in combination with mild heat treatment could be
      used to enhance the inactivation of L. monocytogenes in semi-skim milk.

PMID- 22633801
TI  - [All-cause and cause-specific mortality in the immigrant and native-born
      populations in Andalusia (Spain)].
AB  - OBJECTIVE: To compare mortality rates between immigrant and native-born residents
      of Andalusia between 2006 and 2010, and to characterize mortality by cause.
      MATERIAL AND METHODS: The data consisted of deaths from mortality statistics by
      cause, and the aggregated populations registered in the lists of inhabitants by
      country of birth in the case of native-born individuals and immigrants (with
      immigrants grouped into six geographical areas of origin). Crude rates and age
      standardized mortality rates (0-39, 40-65 and 65 years and above) were calculated
      by cause of death separately for men and women. RESULTS: In the group aged 0-39
      years, mortality due to external causes was higher in immigrants than in the
      native-born population, especially in African immigrants, with standardized rates
      of 142 and 145 deaths per 100,000 persons/year in women and men, respectively.
      Deaths due to maternal-related factors were particularly high among Africans. In
      the group aged 40-64 years, mortality rates were higher in immigrant women than
      in native-born women but were lower in immigrant men than in native-born men; in
      this age group, mortality was particularly high in African women and men from
      Europe and North America. In the group aged 65 years and over, mortality was
      higher in the native-born population of both genders than in immigrants due to
      cancer and cardiovascular disease. CONCLUSIONS: The differences in mortality
      between immigrants and native-born residents varied depending on age, gender,
      cause of death and birthplace. Notable findings were the higher mortality among
      elderly native-born residents, due to chronic degenerative diseases, and the high
      mortality in the Sub-Saharan population at younger ages due to accidents.

PMID- 22633802
TI  - Combination of CK20 and Ki-67 immunostaining analysis predicts recurrence,
      progression, and cancer-specific survival in pT1 urothelial bladder cancer.
AB  - BACKGROUND: The prognostic value of CK20, Ki-67, and p53 has been investigated
      for non-muscle-invasive urothelial bladder cancers but not for the distinct and
      clinically challenging subset of pT1 bladder cancers. OBJECTIVE: To evaluate the
      prognostic value of CK20, Ki-67, and p53 within the largest series of pT1
      urothelial bladder cancers. DESIGN, SETTING, AND PARTICIPANTS: Data from 309
      patients with pT1 urothelial bladder cancer from one single urologic centre were
      collected. INTERVENTION: Adjuvant instillation of bacillus Calmette-Guerin was
      performed in each patient. A second resection was performed after 4-8 wk. A total
      of 76 patients underwent cystectomy. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: We conducted histomorphologic analysis; immunohistochemistry for CK20,
      Ki-67, and p53; and univariate and multivariate Cox regression models including
      recurrence-free survival (RFS), progression-free survival (PFS), and cancer
      specific survival (CSS). RESULTS AND LIMITATIONS: At a median follow-up of 49 mo,
      we found recurrence and progression and disease-specific mortality rates of
      22.7%, 20.1%, and 15.9%, respectively. CK20 expression was significantly
      correlated with RFS in multivariate analysis (hazard ratio [HR]: 5.89; 95%
      confidence interval [CI], 1.44-24.15; p=0.014). In multivariate analysis, Ki-67
      was the only marker significantly correlated with PFS (HR: 2.80; 95% CI, 1.45
      5.43, p=0.002). Ki-67 (HR: 3.83; 95% CI, 1.59-9.26; p=0.003), and CK20 (HR: 8.44;
      95% CI,1.16-61.34; p=0.035) were significantly correlated with CSS in
      multivariate analysis. The combination of CK20 and Ki-67 showed significantly
      worse RFS (p=0.026), PFS (p=0.003), and CSS (p<0.001) in tumours with a high
      proliferation index and abnormal CK20 expression. A retrospective study design
      was the major limitation of this study. CONCLUSIONS: Our present analysis of the
      largest series of patients with pT1 urothelial bladder cancer published to date
      found Ki-67 and CK20 to be potential prognostic markers improving the risk
      stratification of pT1 bladder tumours. They are reliable indicators of biologic
      aggressiveness and may contribute to decision making on therapeutic strategy for
      pT1 bladder carcinomas.

PMID- 22633804
TI  - [Management of acromegaly in pregnancy: case report and literature review].

PMID- 22633803
TI  - Early salvage radiation therapy does not compromise cancer control in patients
      with pT3N0 prostate cancer after radical prostatectomy: results of a match
      controlled multi-institutional analysis.
AB  - BACKGROUND: Previous randomised trials demonstrated that adjuvant radiation
      therapy (aRT) improves cancer control in patients with pT3 prostate cancer (PCa).
      However, there is currently no evidence supporting early salvage radiation
      therapy (eSRT) as equivalent to aRT in improving freedom from biochemical
      recurrence (BCR) after radical prostatectomy (RP). OBJECTIVE: To evaluate BCR
      free survival for aRT versus observation followed by eSRT in cases of relapse in
      patients undergoing RP for pT3pN0, R0-R1 PCa. DESIGN, SETTING, AND PARTICIPANTS:
      Using a European multi-institutional cohort, 890 men with pT3pN0, R0-R1 PCa were
      identified. INTERVENTION: All patients underwent RP. Subsequently, patients were
      stratified into two groups: aRT versus initial observation followed by eSRT in
      cases of relapse. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Propensity
      matched analysis was employed, and patients were stratified into two groups: aRT
      versus observation and eventual eSRT, defined as RT given at a postoperative
      serum prostate-specific antigen (PSA) <= 0.5 ng/ml at least 6 mo after RP. BCR,
      defined as PSA >0.20 ng/ml and rising after administration of RT, was compared
      between aRT and initial observation followed by eSRT in cases of relapse using
      Kaplan-Meier and Cox regression methods. RESULTS AND LIMITATIONS: Overall, 390
      (43.8%) and 500 (56.2%) patients were treated with aRT and initial observation,
      respectively. Within the latter group, 225 (45.0%) patients experienced BCR and
      underwent eSRT. In the postpropensity-matched cohort, the 2- and 5-yr BCR-free
      survival rates were 91.4% and 78.4% in aRT versus 92.8% and 81.8% in patients who
      underwent initial observation and eSRT in cases of relapse, respectively (p=0.9).
      No differences in the 2- and 5-yr BCR-free survival rates were found, even when
      patients were stratified according to pT3 substage and surgical margin status
      (all p >= 0.4). These findings were also confirmed in multivariable analyses
      (p=0.6). Similar results were achieved when the cut-off to define eSRT was set at
      0.3 ng/ml (all p >= 0.5). CONCLUSIONS: The current study suggests that timely
      administration of eSRT is comparable to aRT in improving BCR-free survival in the
      majority of pT3pN0 PCa patients. Therefore, eSRT may not compromise cancer
      control but significantly reduces overtreatment associated with aRT.

PMID- 22633805
TI  - Attention samples stimuli rhythmically.
AB  - Overt exploration or sampling behaviors, such as whisking, sniffing, and saccadic
      eye movements, are often characterized by a rhythm. In addition, the
      electrophysiologically recorded theta or alpha phase predicts global detection
      performance. These two observations raise the intriguing possibility that covert
      selective attention samples from multiple stimuli rhythmically. To investigate
      this possibility, we measured change detection performance on two simultaneously
      presented stimuli, after resetting attention to one of them. After a reset flash
      at one stimulus location, detection performance fluctuated rhythmically. When the
      flash was presented in the right visual field, a 4 Hz rhythm was directly visible
      in the time courses of behavioral performance at both stimulus locations, and the
      two rhythms were in antiphase. A left visual field flash exerted only partial
      reset on performance and induced rhythmic fluctuation at higher frequencies (6-10
      Hz). These findings show that selective attention samples multiple stimuli
      rhythmically, and they position spatial attention within the family of
      exploration behaviors.

PMID- 22633806
TI  - The chemical interactions underlying tomato flavor preferences.
AB  - Although human perception of food flavors involves integration of multiple
      sensory inputs, the most salient sensations are taste and olfaction. Ortho- and
      retronasal olfaction are particularly crucial to flavor because they provide the
      qualitative diversity so important to identify safe versus dangerous foods.
      Historically, flavor research has prioritized aroma volatiles present at levels
      exceeding the orthonasally measured odor threshold, ignoring the variation in the
      rate at which odor intensities grow above threshold. Furthermore, the chemical
      composition of a food in itself tells us very little about whether or not that
      food will be liked. Clearly, alternative approaches are needed to elucidate
      flavor chemistry. Here we use targeted metabolomics and natural variation in
      flavor-associated sugars, acids, and aroma volatiles to evaluate the chemistry of
      tomato fruits, creating a predictive and testable model of liking. This
      nontraditional approach provides novel insights into flavor chemistry, the
      interactions between taste and retronasal olfaction, and a paradigm for enhancing
      liking of natural products. Some of the most abundant volatiles do not contribute
      to consumer liking, whereas other less abundant ones do. Aroma volatiles make
      contributions to perceived sweetness independent of sugar concentration,
      suggesting a novel way to increase perception of sweetness without adding sugar.

PMID- 22633807
TI  - Transsynaptic control of presynaptic Ca2+ influx achieves homeostatic
      potentiation of neurotransmitter release.
AB  - Given the complexity of the nervous system and its capacity for change, it is
      remarkable that robust, reproducible neural function and animal behavior can be
      achieved. It is now apparent that homeostatic signaling systems have evolved to
      stabilize neural function. At the neuromuscular junction (NMJ) of organisms
      ranging from Drosophila to human, inhibition of postsynaptic neurotransmitter
      receptor function causes a homeostatic increase in presynaptic release that
      precisely restores postsynaptic excitation. Here we address what occurs within
      the presynaptic terminal to achieve homeostatic potentiation of release at the
      Drosophila NMJ. By imaging presynaptic Ca(2+) transients evoked by single action
      potentials, we reveal a retrograde, transsynaptic modulation of presynaptic
      Ca(2+) influx that is sufficient to account for the rapid induction and sustained
      expression of the homeostatic change in vesicle release. We show that the
      homeostatic increase in Ca(2+) influx and release is blocked by a point mutation
      in the presynaptic CaV2.1 channel, demonstrating that the modulation of
      presynaptic Ca(2+) influx through this channel is causally required for
      homeostatic potentiation of release. Together with additional analyses, we
      establish that retrograde, transsynaptic modulation of presynaptic Ca(2+) influx
      through CaV2.1 channels is a key factor underlying the homeostatic regulation of
      neurotransmitter release.

PMID- 22633809
TI  - Rats answer an unexpected question after incidental encoding.
AB  - A fundamental aspect of episodic memory is that retrieval of information can
      occur when encoding is incidental and memory assessment is unexpected. These
      features are difficult to model in animals because behavioral training likely
      gives rise to well-learned expectations about the sequence of events. Thus, the
      possibility remains that animals may solve an episodic memory test by using well
      learned semantic rules without remembering the episode at memory assessment. Here
      we show that rats can answer an unexpected question after incidental encoding in
      a hippocampal-dependent manner, consistent with the use of episodic memory. Rats
      were initially trained to report about a recent event (food versus no food) and
      separately searched for food where there was no expectation of being asked about
      the presence of food. To test episodic memory, we gave rats the opportunity to
      incidentally encode the presence or absence of food and unexpectedly asked them
      to report about the recent event. Temporary inactivation of the CA3 region of the
      hippocampus with bilateral infusions of lidocaine selectively eliminated the
      ability of rats to answer the unexpected, but not the expected, question. Our
      studies suggest that rats remember an earlier episode after incidental encoding
      based upon hippocampal-dependent episodic memory.

PMID- 22633808
TI  - Melanopsin-based brightness discrimination in mice and humans.
AB  - Photoreception in the mammalian retina is not restricted to rods and cones but
      extends to a small number of intrinsically photoreceptive retinal ganglion cells
      (ipRGCs), expressing the photopigment melanopsin. ipRGCs are known to support
      various accessory visual functions including circadian photoentrainment and
      pupillary reflexes. However, despite anatomical and physiological evidence that
      they contribute to the thalamocortical visual projection, no aspect of visual
      discrimination has been shown to rely upon ipRGCs. Based on their currently known
      roles, we hypothesized that ipRGCs may contribute to distinguishing brightness.
      This percept is related to an object's luminance-a photometric measure of light
      intensity relevant for cone photoreceptors. However, the perceived brightness of
      different sources is not always predicted by their respective luminance. Here, we
      used parallel behavioral and electrophysiological experiments to first show that
      melanopsin contributes to brightness discrimination in both retinally degenerate
      and fully sighted mice. We continued to use comparable paradigms in
      psychophysical experiments to provide evidence for a similar role in healthy
      human subjects. These data represent the first direct evidence that an aspect of
      visual discrimination in normally sighted subjects can be supported by inner
      retinal photoreceptors.

PMID- 22633810
TI  - Overcoming hybridization barriers by the secretion of the maize pollen tube
      attractant ZmEA1 from Arabidopsis ovules.
AB  - A major goal of plant reproduction research is to understand and overcome
      hybridization barriers so that the gene pool of crop plants can be increased and
      improved upon. After successful pollen germination on a receptive stigma, the
      nonmotile sperm cells of flowering plants are transported via the pollen tube
      (PT) to the egg apparatus for the achievement of double fertilization. The PT
      path is controlled by various hybridization mechanisms probably involving a
      larger number of species-specific molecular interactions. The egg-apparatus
      secreted polymorphic peptides ZmEA1 in maize and LURE1 and LURE2 in Torenia
      fournieri as well as TcCRP1 in T. concolor were shown to be required for
      micropylar PT guidance, the last step of the PT journey. We report here that
      ZmEA1 attracts maize PTs in vitro and arrests their growth at higher
      concentrations. Furthermore, it binds to the subapical region of maize PT tips in
      a species-preferential manner. To overcome hybridization barriers at the level of
      gametophytic PT guidance, we expressed ZmEA1 in Arabidopsis synergid cells.
      Secreted ZmEA1 enabled Arabidopsis ovules to guide maize PT in vitro in a species
      preferential manner to the micropylar opening of the ovule. These results
      demonstrate that the egg-apparatus-controlled reproductive-isolation barrier of
      PT guidance can be overcome even between unrelated plant families.

PMID- 22633811
TI  - Larval export from marine reserves and the recruitment benefit for fish and
      fisheries.
AB  - Marine reserves, areas closed to all forms of fishing, continue to be advocated
      and implemented to supplement fisheries and conserve populations. However,
      although the reproductive potential of important fishery species can dramatically
      increase inside reserves, the extent to which larval offspring are exported and
      the relative contribution of reserves to recruitment in fished and protected
      populations are unknown. Using genetic parentage analyses, we resolve patterns of
      larval dispersal for two species of exploited coral reef fish within a network of
      marine reserves on the Great Barrier Reef. In a 1,000 km(2) study area,
      populations resident in three reserves exported 83% (coral trout, Plectropomus
      maculatus) and 55% (stripey snapper, Lutjanus carponotatus) of assigned offspring
      to fished reefs, with the remainder having recruited to natal reserves or other
      reserves in the region. We estimate that reserves, which account for just 28% of
      the local reef area, produced approximately half of all juvenile recruitment to
      both reserve and fished reefs within 30 km. Our results provide compelling
      evidence that adequately protected reserve networks can make a significant
      contribution to the replenishment of populations on both reserve and fished reefs
      at a scale that benefits local stakeholders.

PMID- 22633812
TI  - Prospective analysis of patient-reported late toxicity following pelvic
      radiotherapy for gynaecological cancer.
AB  - BACKGROUND AND PURPOSE: As late radiotherapy toxicity impacts negatively on the
      quality-of-life of cancer survivors and is often under reported, a study was set
      up to prospectively collect patient-reported data in an unselected series of
      patients with gynaecological malignancy. Aim 1 - To provide 3 year results for
      the longitudinal study. Aim 2 - To improve the questionnaire used to collect data
      by identifying redundant items and modifying for use to collect Common
      Terminology Criteria for Adverse Events (CTCAE) data. MATERIAL AND METHODS: Aim 1
      - Patient reported outcome data were collected prospectively by 226 patients
      before and up to 3 years following radiotherapy for gynaecological cancer using a
      questionnaire developed to collect LENT subjective data. Aim 2 - A factor
      analysis was performed to identify which questions gave the most and least
      information. RESULTS: Aim 1 - Faecal urgency and incontinence (all grades) peaked
      at 79% and 24%, respectively at 1 year then settled to 69% and 18% at 3 years,
      respectively. Urinary urgency (all grades) increased with time and was described
      in 75% at 3 years. Other symptoms reported at 3 years include diarrhoea in 12%,
      urinary incontinence in 27% and vaginal dryness in 29%. A third of patients did
      not feel their sex life had changed following treatment, while a quarter felt
      that it had. Aim 2 - some questions overlapped and others were non-specific. The
      questionnaire has subsequently been altered. CONCLUSIONS: The extent of late
      toxicity is substantial. This detailed information is important for both patients
      and clinicians in terms of treatment decisions and follow-up care. The LENT
      questionnaire provides a feasible tool for capture of this information in the
      clinic.

PMID- 22633813
TI  - Impact of dosimetric and clinical parameters on clinical side effects in cervix
      cancer patients treated with 3D pulse-dose-rate intracavitary brachytherapy.
AB  - BACKGROUND AND PURPOSE: To assess the association between dosimetric/clinical
      parameters and gastrointestinal/urinary grade 2-4 side effects in cervix cancer
      patients treated with 3D pulse dose rate brachytherapy. MATERIALS AND METHODS:
      Three hundred and fifty-two patients received brachytherapy associated with
      external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent
      surgery. The doses for the most exposed 2, and 0.1 cm(3) (D(2cc) and D(0.1cc))
      volumes of the rectum and bladder as well as bladder ICRU point dose (D(ICRU))
      were converted into isoeffective doses in 2-Gy fractions. The clinical parameters
      analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery,
      FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side
      effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were
      defined separately for patients treated with EBRT and brachytherapy (Group 1) and
      with preoperative brachytherapy (Group 2). RESULTS: The median follow-up was
      23.4months. In Group 1 a significant predictive value of rectum D(0.1cc) and
      D(2cc), bladder D(0.1cc) and D(ICRU) for gastrointestinal and urinary toxicity
      was found using as cutoff 83, 68, 109 and 68Gy(alpha)(/)(beta)(3). In Group 2 a
      significant predictive value of bladder D(0.1cc), D(2cc) and D(ICRU) for urinary
      toxicity was found using as cutoff 141, 91 and 67Gy(alpha)(/)(beta)(3), but not
      for the rectum D(0.1cc) and D(2cc); smoking had a significant predictive value on
      urinary toxicity. CONCLUSIONS: For patients treated with brachytherapy and EBRT,
      rectum D(0.1cc) and D(2cc) and bladder D(0.1cc) and D(ICRU) had a predictive
      value for toxicity. For patients treated with preoperative brachytherapy, bladder
      D(0.1cc), D(2cc) and D(ICRU) and smoking had a predictive value for urinary
      toxicity.

PMID- 22633814
TI  - Residual setup errors caused by rotation and non-rigid motion in prone-treated
      cervical cancer patients after online CBCT image-guidance.
AB  - PURPOSE: To quantify the impact of uncorrected or partially corrected pelvis
      rotation and spine bending on region-specific residual setup errors in prone
      treated cervical cancer patients. METHODS AND MATERIALS: Fifteen patients
      received an in-room CBCT scan twice a week. CBCT scans were registered to the
      planning CT-scan using a pelvic clip box and considering both translations and
      rotations. For daily correction of the detected translational pelvis setup errors
      by couch shifts, residual setup errors were determined for L5, L4 and seven other
      points of interest (POIs). The same was done for a procedure with translational
      corrections and limited rotational correction (+/-3 degrees ) by a 6D positioning
      device. RESULTS: With translational correction only, residual setup errors were
      large especially for L5/L4 in AP direction (Sigma=5.1/5.5mm). For the 7 POIs the
      residual setup errors ranged from 1.8 to 5.6mm (AP). Using the 6D positioning
      device, the errors were substantially smaller (for L5/L4 in AP direction
      Sigma=2.7/2.2mm). Using this device, the percentage of fractions with a residual
      AP displacement for L4>5mm reduced from 47% to 9%. CONCLUSIONS: Setup variations
      caused by pelvis rotations are large and cannot be ignored in prone treatment of
      cervical cancer patients. Corrections with a 6D positioning device may
      considerably reduce resulting setup errors, but the residual setup errors should
      still be accounted for by appropriate CTV-to-PTV margins.

PMID- 22633815
TI  - EORTC Radiation Oncology Group quality assurance platform: establishment of a
      digital central review facility.
AB  - OBJECTIVE: Quality assurance (QA) in clinical trials is essential to ensure
      treatment is safely and effectively delivered. As QA requirements have increased
      in complexity in parallel with evolution of radiation therapy (RT) delivery, a
      need to facilitate digital data exchange emerged. Our objective is to present the
      platform developed for the integration and standardization of QART activities
      across all EORTC trials involving RT. METHODS: The following essential
      requirements were identified: secure and easy access without on-site software
      installation; integration within the existing EORTC clinical remote data capture
      system; and the ability to both customize the platform to specific studies and
      adapt to future needs. After retrospective testing within several clinical
      trials, the platform was introduced in phases to participating sites and QART
      study reviewers. RESULTS: The resulting QA platform, integrating RT analysis
      software installed at EORTC Headquarters, permits timely, secure, and fully
      digital central DICOM-RT based data review. Participating sites submit data
      through a standard secure upload webpage. Supplemental information is submitted
      in parallel through web-based forms. An internal quality check by the QART office
      verifies data consistency, formatting, and anonymization. QART reviewers have
      remote access through a terminal server. Reviewers evaluate submissions for
      protocol compliance through an online evaluation matrix. Comments are collected
      by the coordinating centre and institutions are informed of the results.
      CONCLUSIONS: This web-based central review platform facilitates rapid, extensive,
      and prospective QART review. This reduces the risk that trial outcomes are
      compromised through inadequate radiotherapy and facilitates correlation of
      results with clinical outcomes.

PMID- 22633816
TI  - Three-dimensional imaging reveals the spatial separation of gammaH2AX-MDC1-53BP1
      and RNF8-RNF168-BRCA1-A complexes at ionizing radiation-induced foci.
AB  - BACKGROUND AND PURPOSE: Ionizing radiation (IR)-induced DNA damage causes the
      accumulation of DNA damage response (DDR) proteins as visible foci in cell
      nuclei. Despite the identified functional roles in DNA repair, the spatial
      relationships of different DDR proteins at foci have not been explicitly
      examined. This study aims to systematically compare the distribution of DDR
      proteins at IR-induced foci. MATERIALS AND METHODS: MCF-7 cells were treated with
      IR, stained for gammaH2AX, MDC1, RNF8, RNF168, 53BP1, Abraxas (CCDC98), BRCA1,
      BRCC36, Merit40 (NBA1) and RAP80, and then imaged using high-resolution three
      dimensional (3-D) confocal microscopy to assess the relative localization of
      proteins at foci. RESULTS: All BRCA1-A complex components displayed strong co
      localization, which overlapped significantly with RNF8 and RNF168, but not with
      gammaH2AX and MDC1. Intriguingly, 53BP1 co-located well with gammaH2AX and MDC1,
      but remained separate from RNF8 and RNF168. These co-localization patterns were
      consistent for at least 3h after IR. CONCLUSIONS: The foci formations of
      gammaH2AX-MDC1-53BP1 and RNF8-RNF168-BRCA1-A complexes are spatially independent.
      Such divergence was not anticipated from prior studies on the recruitment of
      these proteins to foci. This information indicates that individual foci may
      represent distinct sites of DNA repair facilitated by a specific subset of DDR
      proteins.

PMID- 22633817
TI  - Effects of a dietary intervention on acute gastrointestinal side effects and
      other aspects of health-related quality of life: a randomized controlled trial in
      prostate cancer patients undergoing radiotherapy.
AB  - PURPOSE: To study the effect of a dietary intervention on acute gastrointestinal
      side effects and other aspects of health-related quality of life (HRQOL) in
      prostate cancer patients referred to radiotherapy. MATERIALS AND METHODS: A total
      of 130 patients were randomly assigned to one of two groups: an intervention
      group (IG, n=64), instructed to reduce their intake of insoluble dietary fibres
      and lactose, a standard care group (SC, n=66), instructed to continue their
      normal diet. Gastrointestinal side effects and other aspects of HRQOL were
      evaluated from baseline up to 2 months after completed radiotherapy, using the
      EORTC QLQ-C30 and QLQ-PR25 and the study-specific Gastrointestinal Side Effects
      Questionnaire (GISEQ). A scale indicating adherence to dietary instructions was
      developed from a Food Frequency Questionnaire (FFQ), with lower scores
      representing better compliance. Descriptive and inferential statistical analyses
      were conducted. RESULTS: There was an interaction effect between randomization
      and time in the FFQ Scores (p<0.001), indicating that both groups followed their
      assigned dietary instructions. The dietary intervention had no effect on
      gastrointestinal side effects or other aspects of HRQOL. During radiotherapy, the
      percentage of patients with bowel symptoms and bloated abdomen was lower in IG
      compared to SC, but the between-group differences were not statistically
      significant. During radiotherapy, the percentage of patients with bowel symptoms,
      urinary symptoms, pain, fatigue and diminished physical and role functioning
      increased in both groups. CONCLUSIONS: The dietary intervention had no effect on
      gastrointestinal side effects or other aspects of HRQOL. The tendency towards
      lower prevalence of bowel symptoms in IG may indicate some positive effect of the
      dietary intervention, but methodological refinements, clearer results and longer
      follow-up are needed before the value of diet change can be established with
      certainty.

PMID- 22633818
TI  - Sinorhizobium americanum symbiovar mediterranense is a predominant symbiont that
      nodulates and fixes nitrogen with common bean (Phaseolus vulgaris L.) in a
      Northern Tunisian field.
AB  - A total of 40 symbiotic bacterial strains isolated from root nodules of common
      bean grown in a soil located in the north of Tunisia were characterized by PCR
      RFLP of the 16S rRNA genes. Six different ribotypes were revealed. Nine
      representative isolates were submitted to phylogenetic analyses of rrs, recA,
      atpD, dnaK, nifH and nodA genes. The strains 23C40 and 23C95 representing the
      most abundant ribotype were closely related to Sinorhizobium americanum CFNEI
      156(T). S. americanum was isolated from Acacia spp. in Mexico, but this is the
      first time that this species is reported among natural populations of rhizobia
      nodulating common bean. These isolates nodulated and fixed nitrogen with this
      crop and harbored the symbiotic genes of the symbiovar mediterranense. The
      strains 23C2 and 23C55 were close to Rhizobium gallicum R602sp(T) but formed a
      well separated clade and may probably constitute a new species. The sequence
      similarities with R. gallicum type strain were 98.7% (rrs), 96.6% (recA), 95.8%
      (atpD) and 93.4% (dnaK). The remaining isolates were, respectively, affiliated to
      R. gallicum, E. meliloti, Rhizobium giardinii and Rhizobium radiobacter. However,
      some of them failed to re-nodulate their original host but promoted root growth.

PMID- 22633819
TI  - Involvement of G1-to-S transition and AhAUX-dependent auxin transport in abscisic
      acid-induced inhibition of lateral root primodia initiation in Arachis hypogaea
      L.
AB  - Previous study indicated that increasing endogenous abscisic acid (ABA) level
      could inhibit the lateral root (LR) formation of peanuts. In this study, we
      investigated the mechanisms by which ABA regulated lateral root primordia (LRP)
      initiation in peanuts (Arachis hypogaea L). Results suggested that ABA inhibited
      LRP initiation through blocking G1-to-S transition in seedlings and mature roots:
      e.g. 5.8% increase in the proportion of G1 phase and 18% decrease in the
      proportion of S phase after ABA treatment for 6 days. Further study of the
      expression of the cell cycle marker gene for G2-to-M transition in peanut roots
      suggested that AhCYCB1 expression was regulated by ABA. We also investigated the
      cooperative regulation of LRP initiation by ABA and indole-3-acetic acid (IAA).
      ABA treatment greatly reduced the effects of endogenous IAA on mature roots. The
      expression of the IAA polar transport gene AhAUX1 appeared to be regulated by ABA
      since ABA inhibited auxin-mediated LRP initiation by suppressing AhAUX-dependent
      auxin transport in peanut roots. We further examined the effect of ABA on the
      expression of DR5::GUS and AtAUX1 in the model plant Arabidopsis. The results of
      Arabidopsis were consistent with that of the peanut.

PMID- 22633820
TI  - Expression of AtSAP5 in cotton up-regulates putative stress-responsive genes and
      improves the tolerance to rapidly developing water deficit and moderate heat
      stress.
AB  - The regulation of gene expression is a key factor in plant acclimation to stress,
      and it is thought that manipulation of the expression of critical stress
      responsive genes should ultimately provide increased protection against abiotic
      stress. The aim of this study was to test the hypothesis that the ectopic
      expression of the AtSAP5 (AT3G12630) gene in transgenic cotton (Gossypium
      hirsutum, cv. Coker 312) will improve tolerance to drought and heat stress by up
      regulating the expression of endogenous stress-responsive genes. The SAP5 gene is
      a member of the stress-associated family of genes that encode proteins containing
      A20/AN1 zinc finger domains. Under non-stressful conditions, cotton plants that
      expressed the AtSAP5 gene showed elevated expression of at least four genes
      normally induced during water deficit or heat stress. The rate of net CO(2)
      assimilation A for three of four transgenic lines tested was less sensitive to
      rapidly developing water deficit over 4d than untransformed wild-type plants, but
      the recovery of A following drought was not significantly affected. The enhanced
      protection of photosynthesis during drought was determined to be primarily at the
      biochemical level, since the extent of stomatal closure was not significantly
      different for all genotypes. Expression of AtSAP5 resulted in the complete
      protection of photosystem (PS) II complexes from photodamage at mid-day after 4 d
      of drought, whereas wild-type plants experienced a 20% decline in active
      photosystem II (PSII) complexes. In addition, enhanced protection of seedling
      growth and leaf viability was associated with the expression of AtSAP5. Since A
      for the transgenic plants was significantly more heat tolerant than A for wild
      type plants, we conclude that ectopic expression of SAP genes is a potentially
      viable approach to improving carbon gain and productivity for cotton grown in
      semi-arid regions with severe drought and heat stress.

PMID- 22633821
TI  - [Presentation of two cases of Crouzon syndrome: allelic cranio-stenotic
      conditions of FGFR genes].
AB  - INTRODUCTION: Craniosynostosis is an abnormal and premature fusion of any cranial
      suture. Twenty per cent of them involve any specific syndrome with Mendelian
      transmission; the other 80% are "non syndromic", although but 10-14% of them are
      genetically transmitted. Using the experience of two patients with Crouzon
      syndrome, a clinical and genetic review is performed. PATIENTS AND METHODS:
      Patient 1: girl of 35 days of age with progressive macrocephaly, protrusion of
      fontanel, ocular proptosis, hypertelorism and divergent strabismus. Cranial RX
      with sagittal synostosis. Surgical operation was performed with 3 months and 8
      months of age due to development of pansynostosis. Patient 2: boy of 3 years 8
      months of age with headaches of migrainous type of one year onset. He had
      acanthosis nigricans. Cranial RX and cerebral CT with evident digital markings
      and fundus of eye with undefined papillary limits, but 18 month later oedematous
      papilla were evident and pansynostosis was detected, so surgery was performed.
      RESULTS: We present a patient with classical Crouzon syndrome (patient 1) and
      another with acanthosis nigricans (patient 2), both diagnosed by the description
      of characteristic clinical features. CONCLUSIONS: Ten craniosynostotic clinical
      forms are currently known as allelic variations of the FGFR genes, and as such
      have reviewed them. As in our two cases, in syndromic types is very important the
      accurate study of the phenotype to orientate the diagnosis, although the
      molecular study will confirm it in many patients and genetic counselling offered.

PMID- 22633822
TI  - Light-controlled synthetic gene circuits.
AB  - Highly complex synthetic gene circuits have been engineered in living organisms
      to develop systems with new biological properties. A precise trigger to activate
      or deactivate these complex systems is desired in order to tightly control
      different parts of a synthetic or natural network. Light represents an excellent
      tool to achieve this goal as it can be regulated in timing, location, intensity,
      and wavelength, which allows for precise spatiotemporal control over genetic
      circuits. Recently, light has been used as a trigger to control the biological
      function of small molecules, oligonucleotides, and proteins involved as parts in
      gene circuits. Light activation has enabled the construction of unique systems in
      living organisms such as band-pass filters and edge-detectors in bacterial cells.
      Additionally, light also allows for the regulation of intermediate steps of
      complex dynamic pathways in mammalian cells such as those involved in kinase
      networks. Herein we describe recent advancements in the area of light-controlled
      synthetic networks.

PMID- 22633823
TI  - Inhibition of PCSK9 in familial hypercholesterolaemia.

PMID- 22633824
TI  - Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low
      density lipoprotein cholesterol in patients with heterozygous familial
      hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a
      phase 2 randomised controlled trial.
AB  - BACKGROUND: Inhibition of proprotein convertase subtilisin/kexin type 9 serine
      protease (PCSK9) resulted in large reductions of low-density lipoprotein
      cholesterol (LDL-C) in phase 1 trials. We assessed the efficacy and safety of
      various doses and dosing intervals of REGN727, a monoclonal antibody to PCSK9,
      added to statins, to further lower LDL-C in patients with heterozygous familial
      hypercholesterolaemia. METHODS: This multicentre, randomised, placebo-controlled
      phase 2 trial was done at 16 lipid clinics in the USA and Canada. Between Jan 18,
      2011, and Nov 7, 2011, we enrolled adults with heterozygous familial
      hypercholesterolaemia and LDL-C concentrations of 2.6 mmol/L or higher on stable
      diet and statin dose, with or without ezetimibe. Patients were randomly assigned
      to receive REGN727 150 mg, 200 mg, or 300 mg every 4 weeks, or 150 mg every 2
      weeks, or placebo every 2 weeks (ratio 1:1:1:1:1). Randomisation was stratified
      by concomitant use of ezetimibe at baseline. Investigators, study staff, and
      patients were masked to treatment group. Blinding was maintained by
      administration of placebo alternating with REGN727 for the groups of 4 week
      dosing. The primary endpoint was mean percent reduction in LDL-C from baseline at
      week 12 and was analysed in the modified intention-to-treat population with an
      analysis of covariance (ANCOVA) model with treatment group. This trial is
      registered in ClinicalTrials.gov, number NCT 01266876. FINDINGS: 77 patients were
      randomly assigned to study groups (15-16 patients per group) and all were
      analysed. Least-squares (LS) mean LDL-C reduction from baseline to week 12 was
      28.9% (SE 5.08) for 150 mg every 4 weeks (p=0.0113), 31.54% (4.91) for 200 mg
      every 4 weeks (p=0.0035), 42.53% (5.09) for 300 mg every 4 weeks (p<0.0001), and
      67.90% (4.85) for 150 mg every 2 weeks (p<0.0001), compared with 10.65% (5.04)
      with placebo. One serious adverse event was reported with placebo and none with
      REGN727. No increases of more than three times the upper limit of normal were
      reported for hepatic transaminases or creatinine kinase. The most common adverse
      event was injection-site reaction with one patient in the group of 300 mg REGN727
      terminating treatment. INTERPRETATION: REGN727 was well tolerated and achieved
      substantial further LDL-C reduction in patients with heterozygous familial
      hypercholesterolaemia and elevated LDL-C treated with high-dose statins, with or
      without ezetimibe. REGN727 has the potential to provide optimum control of LDL-C
      in patients with this disorder. FUNDING: Sanofi US and Regeneron Pharmaceuticals
      Incorporated.

PMID- 22633826
TI  - Magnesium and neuroprotection in subarachnoid haemorrhage.

PMID- 22633825
TI  - Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo
      controlled trial.
AB  - BACKGROUND: Magnesium sulphate is a neuroprotective agent that might improve
      outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or
      improving the outcome of delayed cerebral ischaemia. We did a trial to test
      whether magnesium therapy improves outcome after aneurysmal subarachnoid
      haemorrhage. METHODS: We did this phase 3 randomised, placebo-controlled trial in
      eight centres in Europe and South America. We randomly assigned (with computer
      generated random numbers, with permuted blocks of four, stratified by centre)
      patients aged 18 years or older with an aneurysmal pattern of subarachnoid
      haemorrhage on brain imaging who were admitted to hospital within 4 days of
      haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo.
      We excluded patients with renal failure or bodyweight lower than 50 kg. Patients,
      treating physicians, and investigators assessing outcomes and analysing data were
      masked to the allocation. The primary outcome was poor outcome-defined as a score
      of 4-5 on the modified Rankin Scale-3 months after subarachnoid haemorrhage, or
      death. We analysed results by intention to treat. We also updated a previous meta
      analysis of trials of magnesium treatment for aneurysmal subarachnoid
      haemorrhage. This study is registered with controlled-trials.com (ISRCTN
      68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36). FINDINGS:
      1204 patients were enrolled, one of whom had his treatment allocation lost. 606
      patients were assigned to the magnesium group (two lost to follow-up), 597 to the
      placebo (one lost to follow-up). 158 patients (26.2%) had poor outcome in the
      magnesium group compared with 151 (25.3%) in the placebo group (risk ratio [RR]
      1.03, 95% CI 0.85-1.25). Our updated meta-analysis of seven randomised trials
      involving 2047 patients shows that magnesium is not superior to placebo for
      reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0.96, 95%
      CI 0.86-1.08). INTERPRETATION: Intravenous magnesium sulphate does not improve
      clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine
      administration of magnesium cannot be recommended. FUNDING: Netherlands Heart
      Foundation, UK Medical Research Council.

PMID- 22633827
TI  - Histopathological lesions associated with equine periodontal disease.
AB  - Equine periodontal disease (EPD) is a common and painful condition, the aetiology
      and pathology of which are poorly understood. To characterise the
      histopathological lesions associated with EPD, the skulls of 22 horses were
      assessed grossly for the presence of periodontal disease, and a standard set of
      interdental tissues taken from each for histopathological examination.
      Histological features of EPD included ulceration and neutrophilic inflammation of
      the gingival epithelium. Mononuclear and eosinophilic inflammation of the
      gingival lamina propria and submucosa was commonly present irrespective of the
      presence or degree of periodontal disease. Gingival hyperplasia was present to
      some degree in all horses, and was only weakly associated with the degree of
      periodontal disease. In all horses dental plaque was present at the majority of
      sites examined and was often associated with histological evidence of peripheral
      cemental erosion. Bacteria (including spirochaetes in four horses) were
      identified in gingival samples by Gram and silver impregnation techniques and
      were significantly associated with the presence of periodontal disease. This is
      the first study to describe histological features of EPD, and the first to
      identify associated spirochaetes in some cases. Histological features were
      variable, and there was considerable overlap of some features between the normal
      and diseased gingiva. Further investigation into the potential role of bacteria
      in the pathogenesis and progression of EPD is warranted.

PMID- 22633828
TI  - Use of sentinel serosurveillance of mules and donkeys in the monitoring of West
      Nile virus infection.
AB  - A cross-sectional study was carried out on clinically normal mules and donkeys in
      a region of southern Spain to assess the seroprevalence of West Nile virus (WNV)
      following detection of infection in contiguous horse and human populations.
      Antibodies against WNV were detected by a blocking ELISA and micro-virus
      neutralisation test in 12/165 (7.3%; CI(95%) 4.3-11.3) of the animals sampled.
      Even though the individual seroprevalence was higher in mules (9.6%; 8/83) than
      in donkeys (4.9%; 4/82), the difference was not statistically significant. Nine
      of 90 herds (10.0%; CI(95%) 3.8-16.2) contained at least one seropositive animal.
      Antibodies against WNV were also detected in 1/4 (25%) donkeys tested on three
      farms where WNV cases had been confirmed in horses. None of 26 potential
      explanatory variables was identified as a risk factor for seropositivity. Such
      serosurveillance of sentinel mules or donkeys may be a useful tool in the
      epidemiological monitoring of WNV in regions where horses are vaccinated.

PMID- 22633829
TI  - Congenital chondrodystrophy of unknown origin in beef herds.
AB  - Congenital chondrodystrophy of unknown origin (CCUO), often referred to as 'acorn
      calf disease' or congenital joint laxity and dwarfism (CJLD), has been reported
      in beef cattle in Canada, the United States, Europe, South Africa, New Zealand
      and Australia. An association of CCUO with grazing drought-affected pastures,
      feeding hay-only or silage-only diets or supplementation with apple pulp suggests
      a nutritional cause such as a mineral deficiency. This review compares published
      reports on CCUO in order to identify common features among outbreaks and to
      provide a basis for future research into the condition. A protocol for
      investigation of outbreaks is provided to improve the outcome of future
      comparisons.

PMID- 22633830
TI  - The effect of partial weight bearing in a walking boot on plantar pressure
      distribution and center of pressure.
AB  - Physicians routinely prescribe partial weight bearing in a walking boot following
      fractures of the lower limbs in order to produce the needed mechanical
      environment to facilitate healing. Plantar pressure measurements can provide key
      information regarding the mechanical environment experienced by lower limb bones.
      The effect of walking boots on plantar pressure distribution has been well
      reported, however, the combined effects of partial weight bearing and walking
      boots on plantar pressure distribution and center of pressure is unknown.
      Thirteen healthy volunteers with no known gait pathologies were fitted with a
      multi-pressure sensor insole that recorded their plantar pressure distribution
      during four walking trials: (i) normal walking, (ii) full weight bearing in a
      walking boot, (iii) 27 kg partial weight bearing in a walking boot and (iv) 9 kg
      partial weight bearing in a walking boot. Results demonstrated that changing from
      trial (i) to (iv) resulted in a posterior shift in weight distribution; the
      percentage of total weight experienced at the heel increased while the percentage
      of total weight experienced at the forefoot (both medial and lateral) and the
      hallux decreased. Center of pressure trajectories also shifted more posteriorly.
      Additionally, while in a walking boot the gait during full and partial weight
      bearing resulted in more even foot loading.

PMID- 22633831
TI  - Synthesis of friedelan triterpenoid analogs with DNA topoisomerase IIalpha
      inhibitory activity and their molecular docking studies.
AB  - Five highly oxygenated friedelan derivatives (3a, 3b, 4, 5a and 5b) were
      synthesized. The structures of these compounds were established on the basis of
      spectral (IR, 1D and 2D NMR, MS etc.) and chemical data. The molecules, including
      the parent compounds were screened for three-dimensional (3D) molecular docking
      on the crystal structure of topoisomerase IIalpha (1 bgw for topoisomerase
      IIalpha, PDB). Compounds 3a and 5a showed a dose dependent inhibition of
      catalytic activity of human topoisomerase IIalpha.

PMID- 22633832
TI  - Facile synthesis, cytotoxic and antimicrobial activity studies of a new group of
      6-aryl-3-[4-(methylsulfonyl)benzyl]-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines.
AB  - The reaction of 4-(methylsulfonyl)phenylacetohydrazide (3) with carbon disulfide
      and potassium hydroxide followed by hydrazine hydrate gave 4-amino-5-[4
      (methylsulfonyl)benzyl]-4H-[1,2,4]triazole-3-thione (4). The resulting triazole
      was subjected to cyclocondensation reaction with different phenacyl bromides to
      afford 6-substituted-3-[4-(methylsulfonyl)benzyl]-7H-[1,2,4]triazolo[3,4
      b][1,3,4]thiadiazines (5a-i). All structures of the newly synthesized compounds
      were confirmed by IR, NMR, mass spectral studies and elemental analyses. The
      newly synthesized compounds were screened for their cytotoxic, antibacterial and
      antifungal activity. Some of the derivatives have exhibited promising biological
      activity.

PMID- 22633833
TI  - Rational design, synthesis, and pharmacological properties of pyranochalcone
      derivatives as potent anti-inflammatory agents.
AB  - 24 derivatives (5a-x) derived from natural pyranochalcones (I and II) were
      designed and evaluated for their inhibitory potency on the production of nitric
      oxide (NO) in LPS-stimulated RAW264.7 cells. Among them, four compounds (5b, 5d,
      5f, and 5h) exhibited more potent inhibitory effects on iNOS activity and iNOS
      mediated NO production than a positive control indomethacin. Furthermore, 5b
      could significantly suppress the progression of carrageenan-induced hind paw
      edema compared to indomethacin at a dosage of 10 mg/kg/day, and dose-dependently
      ameliorated the development of adjuvant-induced arthritis (AIA) validated by
      arthritic scores and H&E staining of joints. In addition, docking study confirmed
      that 5b was an iNOS inhibitor with binding to the active site of murine iNOS.

PMID- 22633834
TI  - Synthesis and antitumor activity of formononetin nitrogen mustard derivatives.
AB  - A series of formononetin nitrogen mustard derivatives were synthesized and
      evaluated in vitro for their cytotoxicity against five cancer cell lines (SH
      SY5Y, HCT-116, DU-145, Hela and SGC-7901). The pharmacological results showed
      that many of the new derivatives displayed more potent cytotoxicity than alkeran.
      Furthermore, compounds 6d and 6n could induce cell cycle arrest at G2/M phase and
      cell apoptosis.

PMID- 22633835
TI  - The effects of long-term exposure to disease-modifying drugs during pregnancy in
      multiple sclerosis.
AB  - BACKGROUND AND OBJECTIVE: Women with multiple sclerosis (MS) who intend to get
      pregnant are often advised to discontinue disease modifying therapy (DMT) prior
      to conception. This recommendation is not based on medical evidence and may
      interfere with disease control by immunomodulatory drugs. The present study was
      designed to help discuss the effect of DMT for MS on pregnancy and on disease
      course. PATIENTS AND METHODS: Retrospective data from 152 pregnancies of 132
      women with MS were collected by the physician in charge of the case. All data
      were entered into a specific file for qualitative and quantitative statistical
      analysis. RESULTS: From the total group of patients, 89 pregnancies occurred
      without any exposure to MS drugs, while 61 pregnancies occurred with at least
      eight weeks of exposure to MS immunomodulatory drugs. The rate of obstetric and
      neonatal complications was similar in both groups, except for the newborn weight
      and height which was smaller for mothers receiving medications. Mothers' post
      delivery relapse rate and EDSS scores in the follow-up period were significantly
      higher in the absence of treatment. CONCLUSION: It is possible that, with further
      such supportive data, international guidelines on MS treatment in young women who
      intend to get pregnant may need to be revised.

PMID- 22633836
TI  - EASL clinical practical guidelines: management of alcoholic liver disease.

PMID- 22633837
TI  - Quantification of 1,3-dimethylol-5,5-dimethylhydantoin and its decomposition
      products in cosmetics by high-performance liquid chromatography.
AB  - We developed a method to simultaneously and quantitatively measure four compounds
      commonly found in commercial cosmetics: 1,3-dimethylol-5,5-dimethylhydantoin
      (DMDMH) and its decomposition products 1-hydroxymethyl-5,5-dimethylhydantoin (1
      MDMH), 3-hydroxymethyl-5,5-dimethylhydantoin (3-MDMH), and 5,5-dimethylhydantoin
      (DMH). In addition, we succeeded in synthesizing 3-MDMH selectively from DMDMH.
      Our new analytical method involves the use of an HPLC system and an
      octadecylsilanized silica column. HPLC calibration curves for DMDMH, 1-MDMH, 3
      MDMH, and DMH were linear over the wide concentration ranges. In cosmetics whose
      pH is basic, the recovery of 3-MDMH and DMH was substantially higher than 100%,
      whereas that of DMDMH and 1-MDMH was considerably lower than 100%, however, the
      average recovery of the four compounds was in the range of 85-105%. It was
      suggested that the latter tend to decompose to the former. We confirmed that our
      HPLC separation method is suitable for the analysis of dimethyhydantoins without
      the progress of decomposition and should be useful for rapid analysis of these
      compounds in cosmetics.

PMID- 22633838
TI  - Comparative evaluation of pK(a) prediction tools on a drug discovery dataset.
AB  - Due to their impact on pharmacokinetic and pharmacodynamic properties the
      accurate prediction of dissociation constants is of outmost importance in drug
      discovery settings. The prediction accuracy, however, is typically assessed on
      public datasets most likely included in the training sets of the available tools.
      In this work we therefore tested five pK(a) prediction softwares such as ACD,
      Epik, Marvin, PharmaAlgorithm and Pallas on novel, never-published compounds. Our
      dataset consists of 177 pK(a) values of 95 structurally diverse in-house
      compounds prepared for real-life drug discovery programs. The thorough analysis
      of prediction accuracy allowed us identifying the best practice and exploring the
      limitations of the current methods. Mean absolute errors (0.86-1.28) obtained for
      this set of discovery compounds indicates the potential in the improvement of the
      available pK(a) prediction approaches. Limitations were further characterized by
      measuring and evaluating 39 pK(a) values of additional 28 commercially available
      compounds representing the most challenging chemotypes. We believe that these
      results would facilitate further developments and hopefully contribute to the
      necessary improvement of the prediction accuracy.

PMID- 22633839
TI  - Analytical aspects of biosimilarity issues of protein drugs.
AB  - The term "biosimilar" is used to designate a follow-on biologic that meets
      extremely high standards for comparability or similarity to the originator
      biologic drug that is approved for use in the same indications. Use of biosimilar
      products has already decreased the cost of treatment in many regions of the world
      and now a regulatory pathway for approval of these products has been established
      both in US and in the EU. The analytical tests to demonstrate comparability and
      similarity of a biosimilar product to a reference drug with respect to protein
      content, activity, physiochemical integrity, stability, impurities and additives,
      as well as immunogenicity are discussed.

PMID- 22633840
TI  - Minding the stroke business.

PMID- 22633841
TI  - alpha1-Acid glycoprotein induced effects in rat brain microvessel endothelial
      cells.
AB  - alpha1-Acid glycoprotein (AGP) is a positive acute phase protein which is
      elevated 1-10 times during inflammation. Whereas AGP has been reported to have
      immunomodulatory properties, other biological functions of this protein such as
      its effects on the blood-brain barrier (BBB) endothelium are unknown. Tight
      junction (TJ) proteins (ZO-1 and occludin) are crucial in maintaining BBB
      integrity and brain homeostasis. As inflammatory cytokines have been shown to
      alter BBB integrity and TJ protein expression, we hypothesized that AGP changes
      BBB function by stimulating inflammatory cytokines and/or directly modulating TJ
      protein expression. We used primary rat brain microvessel endothelial cells
      (RBMECs) as an in vitro BBB model to study the direct effects of AGP on the brain
      microvasculature. No change in cytokine levels was detected in supernatant from
      AGP-treated RBMECs, despite increased mRNA expression by the cells. Paracellular
      permeability was decreased up to 20%, across RBMEC monolayers following treatment
      with AGP, suggesting its role in enhancing BBB integrity. RBMECs showed a
      biphasic response of increased occludin protein expression following AGP
      treatment while ZO-1 expression changed in a dose- and time-dependent manner.
      These changes in TJ proteins suggest that AGP induced changes in occludin related
      to enhanced barrier properties while the change in ZO-1 may play a secondary role
      in BBB integrity and/or as an intracellular signaling molecule. AGP significantly
      changed transcription factor activator protein 1 (AP-1) DNA-binding activity
      which provides evidence of the potential cell signaling pathways that contribute
      to the effect of AGP in RBMECs. Together, this supports our hypothesis that AGP
      has a direct effect in brain microvasculature and may play an important role in
      altering BBB integrity in inflammatory-related diseases.

PMID- 22633843
TI  - Preliminary examination of a couple-based eating disorder prevention program.
AB  - The purpose of the current study was to investigate a new dissonance-based
      prevention program that is based on the dual pathway model of eating disorders
      within the context of an individual's romantic relationship. A total of 209
      dating couples participated in a couple-based prevention program or an assessment
      only condition and completed measures of body dissatisfaction, thin-ideal
      internalization, disordered eating, negative affect, and relationship
      satisfaction at two time points (approximately one week apart) and approximately
      half of the sample completed 1-month follow-up measures. The prevention program
      significantly reduced several key risk factors for eating disorders such as
      environmental pressures to be thin, internalization of the thin and athletic
      ideals, state body dissatisfaction, and actual-ideal body discrepancy. Initial
      support was found for the inclusion of couples in eating disorder prevention
      programs as a successful way of addressing the thin ideal and its detrimental
      effects for women.

PMID- 22633842
TI  - Phosphatidylinositol 4-kinases: hostages harnessed to build panviral replication
      platforms.
AB  - Several RNA viruses have recently been shown to hijack members of the host
      phosphatidylinositol (PtdIns) 4-kinase (PI4K) family of enzymes. They use PI4K to
      generate membranes enriched in phosphatidylinositide 4-phosphate (PtdIns4P or
      PI4P) lipids, which can be used as replication platforms. Viral replication
      machinery is assembled on these platforms as a supramolecular complex and
      PtdIns4P lipids regulate viral RNA synthesis. This article highlights these
      recent studies on the regulation of viral RNA synthesis by PtdIns4P lipids. It
      explores the potential mechanisms by which PtdIns4P lipids can contribute to
      viral replication and discusses the therapeutic potential of developing antiviral
      molecules that target host PI4Ks as a form of panviral therapy.

PMID- 22633844
TI  - Analysis of Arabidopsis glutathione-transferases in yeast.
AB  - The genome of Arabidopsis thaliana encodes 54 functional glutathione transferases
      (GSTs), classified in seven clades. Although plant GSTs have been implicated in
      the detoxification of xenobiotics, such as herbicides, extensive redundancy
      within this large gene family impedes a functional analysis in planta. In this
      study, a GST-deficient yeast strain was established as a system for analyzing
      plant GSTs that allows screening for GST substrates and identifying substrate
      preferences within the plant GST family. To this end, five yeast genes encoding
      GSTs and GST-related proteins were simultaneously disrupted. The resulting yeast
      quintuple mutant showed a strongly reduced conjugation of the GST substrates 1
      chloro-2,4-dinitrobenzene (CDNB) and 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD
      Cl). Consistently, the quintuple mutant was hypersensitive to CDNB, and this
      phenotype was complemented by the inducible expression of Arabidopsis GSTs. The
      conjugating activity of the plant GSTs was assessed by in vitro enzymatic assays
      and via analysis of exposed yeast cells. The formation of glutathione adducts
      with dinitrobenzene was unequivocally verified by stable isotope labeling and
      subsequent accurate ultrahigh-resolution mass spectrometry (ICR-FTMS). Analysis
      of Arabidopsis GSTs encompassing six clades and 42 members demonstrated
      functional expression in yeast by using CDNB and NBD-Cl as model substrates.
      Subsequently, the established yeast system was explored for its potential to
      screen the Arabidopsis GST family for conjugation of the fungicide anilazine.
      Thirty Arabidopsis GSTs were identified that conferred increased levels of
      glutathionylated anilazine. Efficient anilazine conjugation was observed in the
      presence of the phi, tau, and theta clade GSTs including AtGSTF2, AtGSTF4,
      AtGSTF6, AtGSTF8, AtGSTF10, and AtGSTT2, none of which had previously been known
      to contribute to fungicide detoxification. ICR-FTMS analysis of yeast extracts
      allowed the simultaneous detection and semiquantification of anilazine conjugates
      as well as catabolites.

PMID- 22633845
TI  - Ajugalide-B (ATMA) is an anoikis-inducing agent from Ajuga taiwanensis with
      antiproliferative activity against tumor cells in vitro.
AB  - Ajuga taiwanensis is widely used for the treatment of hepatitis and hepatoma in
      Taiwanese folk medicine. However, its bioactive components and mechanism of
      action are unclear. Herein, ajugalide-B (ATMA), a neoclerodane diterpenoid
      isolated from Ajuga taiwanensis, is reported to exhibit high anti-proliferative
      activity against tumor cell lines from various tissues. These results demonstrate
      that ATMA disrupts the focal adhesion complex by decreasing phosphorylation of
      paxillin and focal adhesion kinase (FAK). As a result, anoikis, a specific type
      of apoptosis caused by detachment of cells, is triggered by activation of caspase
      8 in A549 cells. Furthermore, ATMA also blocks anchorage-independent growth and
      cell migration and, therefore, ATMA may serve as a lead compound for the
      developing of anti-cancer therapeuties with anoikis-inducing properties.

PMID- 22633846
TI  - Alkenylresorcinols and cytotoxic activity of the constituents isolated from
      Labisia pumila.
AB  - Phytochemical investigation on the leaves of Labisia pumila (Myrsinaceae), an
      important medicinal herb in Malaysia, has led to the isolation of 1-O-methyl-6
      acetoxy-5-(pentadec-10Z-enyl)resorcinol (1), labisiaquinone A (2) and
      labisiaquinone B (3). Along with these, 16 known compounds including 1-O-methyl-6
      acetoxy-5-pentadecylresorcinol (4), 5-(pentadec-10Z-enyl)resorcinol (5), 5
      (pentadecyl)resorcinol (6), (-)-loliolide (7), stigmasterol (8), 4
      hydroxyphenylethylamine (9), 3,4,5-trihydroxybenzoic acid (10), 3,4
      dihydroxybenzoic acid (11), (+)-catechin (12), (-)-epicatechin (13), kaempferol-3
      O-alpha-rhamnopyranosyl-7-O-beta-glycopyranoside (14), kaempferol-4'-O-beta
      glycopyranoside (15), quercetin-3-O-alpha-rhamnopyranoside (16), kaempferol-3-O
      alpha-rhamnopyranoside (17), (9Z,12Z)-octadeca-9,12-dienoic acid (18) and
      stigmasterol-3-O-beta-glycopyranoside (19) were also isolated. The structures of
      these compounds were established on the basis of 1D and 2D NMR spectroscopy
      techniques (1H, 13C, COSY, HSQC, NOESY and HMBC experiments), mass spectrometry
      and chemical derivatization. Among the constituents tested 1 and 4 exhibited
      strongest cytotoxic activity against the PC3, HCT116 and MCF-7 cell lines (IC50
      values <= 10 MUM), and they showed selectivity towards the first two-cell lines
      relative to the last one.

PMID- 22633847
TI  - In vitro and in vivo inhibition of Streptococcus mutans biofilm by Trachyspermum
      ammi seeds: an approach of alternative medicine.
AB  - The aim of this study was to evaluate the influence of the crude and active
      solvent fraction of Trachyspermum ammi on S. mutans cariogenicity, effect on
      expression of genes involved in biofilm formation and caries development in rats.
      GC-MS was carried out to identify the major components present in the crude and
      the active fraction of T. ammi. The crude extract and the solvent fraction
      exhibiting least MIC were selected for further experiments. Scanning electron
      microscopy was carried out to observe the effect of the extracts on S. mutans
      biofilm. Comparative gene expression analysis was carried out for nine selected
      genes. 2-Isopropyl-5-methyl-phenol was found as major compound in crude and the
      active fraction. Binding site of this compound within the proteins involved in
      biofilm formation, was mapped with the help of docking studies. Real-time RT-PCR
      analyses revealed significant suppression of the genes involved in biofilm
      formation. All the test groups showed reduction in caries (smooth surface as well
      as sulcal surface caries) in rats. Moreover, it also provides new insight to
      understand the mechanism influencing biofilm formation in S. mutans. Furthermore,
      the data suggest the putative cariostatic properties of T. Ammi and hence can be
      used as an alternative medicine to prevent caries infection.

PMID- 22633848
TI  - [Myocarditis].
AB  - Myocarditis is an inflammatory disease of the myocardium associated with cardiac
      dysfunction. Etiologies of myocarditis are numerous - viral causes being the most
      frequent - as well as their clinical presentations which varies from isolated
      increase in cardiac enzymes during a viral pericarditis, fulminant myocarditis
      associated with cardiogenic shock to endomyocardial biopsy proven inflammation
      discovered during the etiologic diagnosis of a dilated cardiomyopathy. This
      article will discuss the importance of recognition of specific clinical scenarios
      of myocarditis and their echocardiographic presentations that are very useful for
      the etiologic diagnosis and to decide the medical strategy. Recent advances in
      the field of myocarditis concern improvement in understanding the
      pathophysiology, in the diagnostic approach with the use of noninvasive imaging
      (MRI) and molecular biology. However, specific treatment is still limited.
      Clinical trials with antiviral medications are not conclusive, and the medical
      strategies remain mainly based on the symptomatic treatment of heart failure.

PMID- 22633849
TI  - Characterization of a Ca2+/calmodulin-dependent AC1 adenylyl cyclase in a non
      neuronal tissue, the blowfly salivary gland.
AB  - Crosstalk between intracellular signalling pathways is a functionally important
      and widespread phenomenon in cell physiology across phyla. In the salivary gland
      of the blowfly, serotonin induces fluid secretion via parallel activation of both
      the InsP(3)/Ca(2+) and the cAMP/PKA signalling pathways, which interact on
      multiple levels. We have determined the molecular identity of a link between both
      pathways that mediates a Ca(2+)-dependent rise of intracellular cAMP. Whereas
      hydrolysis of cAMP via phosphodiesterases is largely independent of Ca(2+), cAMP
      synthesis by adenylyl cyclases (AC) is potentiated in a Ca(2+)/calmodulin
      (Ca(2+)/CaM)-dependent manner. The existence of a Ca(2+)/CaM-dependent AC is
      supported by physiological data and a molecular approach. We have cloned Cv
      rutabaga cDNA, encoding the first blowfly AC, and confirmed its expression in the
      salivary gland via reverse transcription followed by polymerase chain reaction.
      The putative gene product of Cv rutabaga is a Ca(2+)/CaM-dependent type I AC and
      shows highest homology to Rutabaga from Drosophila. Thus, a Ca(2+)/CaM-dependent
      AC serves as a link between the InsP(3)/Ca(2+) and the cAMP/PKA signalling
      pathways in the salivary gland of the blowfly and might be important for the
      amplification and optimization of the secretory response.

PMID- 22633850
TI  - Temperature-dependent calcium-induced calcium release via InsP3 receptors in
      mouse olfactory ensheathing glial cells.
AB  - Cooling can induce Ca(2+) signaling via activation of temperature-sensitive ion
      channels such as TRPM8, TRPA1 and ryanodine receptor channels. Here we have
      studied the mechanism of cooling-evoked Ca(2+) signaling in mouse olfactory
      ensheathing cells (OECs), a specialized type of glial cells in the olfactory
      nerve layer of the olfactory bulb. Reducing the temperature from above 30 degrees
      C to 28 degrees C and below triggered Ca(2+) transients that persisted in the
      absence of external Ca(2+), but were suppressed after Ca(2+) store depletion by
      cyclopiazonic acid. Cooling-evoked Ca(2+) transients were present in mice
      deficient of TRPM8 and TRPA1, and were not inhibited by ryanodine receptor
      antagonists. Inhibition of InsP(3) receptors with 2-APB and caffeine entirely
      blocked cooling-evoked Ca(2+) transients. Moderate Ca(2+) increases, as evoked by
      flash photolysis of NP-EGTA (caged Ca(2+)) and cyclopiazonic acid, triggered
      InsP(3) receptor-mediated Ca(2+) release at 22 degrees C, but not at 31 degrees
      C. The results suggest that InsP(3) receptors mediate Ca(2+)-induced Ca(2+)
      release in OECs, and that this Ca(2+) release is temperature-sensitive and can be
      suppressed at temperatures above 28 degrees C.

PMID- 22633851
TI  - Fractal properties of macrophage membrane studied by AFM.
AB  - Complexity of cell membrane poses difficulties to quantify corresponding
      morphology changes during cell proliferation and damage. We suggest using fractal
      dimension of the cell membrane to quantify its complexity and track changes
      produced by various treatments. Glutaraldehyde fixed mouse RAW 264.7 macrophage
      membranes were chosen as model system and imaged in PeakForce QNM (quantitative
      nanomechanics) mode of AFM (atomic force microscope). The morphology of the
      membranes was characterized by fractal dimension. The parameter was calculated
      for set of AFM images by three different methods. The same calculations were done
      for the AFM images of macrophages treated with colchicine, an inhibitor of the
      microtubule polymerization, and microtubule stabilizing agent taxol. We conclude
      that fractal dimension can be additional and useful parameter to characterize the
      cell membrane complexity and track the morphology changes produced by different
      treatments.

PMID- 22633852
TI  - Atomic force microscopy on chromosomes, chromatin and DNA: a review.
AB  - The purpose of this review is to discuss the achievements and progress that has
      been made in the use of atomic force microscopy in DNA related research in the
      last 25 years. For this review DNA related research is split up in chromosomal-,
      chromatin- and DNA focused research to achieve a logical flow from large- to
      smaller structures. The focus of this review is not only on the AFM as imaging
      tool but also on the AFM as measuring tool using force spectroscopy, as therein
      lays its greatest advantage and future. The amazing technological and
      experimental progress that has been made during the last 25 years is too
      extensive to fully cover in this review but some key developments and experiments
      have been described to give an overview of the evolution of AFM use from 'imaging
      tool' to 'measurement tool' on chromosomes, chromatin and DNA.

PMID- 22633853
TI  - Characterisation of InAs/GaAs short period superlattices using column ratio
      mapping in aberration-corrected scanning transmission electron microscopy.
AB  - The image processing technique of column ratio mapping was applied to aberration
      corrected high angle annular dark field (HAADF) images of short period MBE
      (molecular beam epitaxy) grown InAs/GaAs superlattices. This method allowed the
      Indium distribution to be mapped and a more detailed assessment of interfacial
      quality to be made. Frozen-phonon multislice simulations were also employed to
      provide a better understanding of the experimental column ratio values. It was
      established that ultra-thin InAs/GaAs layers can be grown sufficiently well by
      MBE. This is despite the fact that the Indium segregated over 3-4 monolayers.
      Furthermore, the effect of the growth temperature on the quality of the layers
      was also investigated. It was demonstrated that the higher growth temperature
      resulted in a better quality superlattice structure.

PMID- 22633855
TI  - A progression of approximations to internal models of complex visuo-motor
      transformations.
AB  - Previous research suggests that the acquisition of an internal model of a complex
      visuo-motor transformation might proceed as a progression of approximations.
      Here, we test this assumption by comparing performance of three groups of
      participants during practice and subsequent open-loop tests with three different
      types of visuo-motor transformation: the kinematic transformation of a sliding
      first-order lever, a point-symmetric transformation, and a line-symmetric
      transformation. With the point-symmetric transformation, participants showed the
      most accurate performance from early practice on and essentially no practice
      benefit. Movements were not systematically biased toward one of the other
      transformations. With the line-symmetric transformation, the initially poorer
      accuracy reached the level of the participants practising the point-symmetric
      transformation rather rapidly. Early in practice movements according to a point
      symmetric transformation were observed. In a similar way the accuracy of
      participants practising the sliding-lever transformation caught up, but remained
      worse at the end of practice, nevertheless. With this transformation movements
      according to a point-symmetric transformation were again observed early in
      practice, and the movements remained biased toward the line-symmetric
      transformation. These findings support the notion that the acquisition of an
      internal model of a complex visuo-motor transformation proceeds in a progression
      of approximations to the accurate internal representation.

PMID- 22633854
TI  - Imaging of articular cartilage--data matching using X-ray tomography, SEM, FIB
      slicing and conventional histology.
AB  - The study was aimed at demonstrating a true cellular resolution for articular
      cartilage using synchrotron radiation-based X-ray microcomputed tomography (SR
      MUCT) with a sample-specific optimization of the phase contrast. The generated
      tomographic data were later used to prepare a matching histological sample from
      the full volume specimen. We used highly coherent and monochromatic X-rays from a
      synchrotron source to image a tissue sample of bovine articular cartilage after
      deparaffinization. Phase contrast enhancement was achieved by using five
      different sample to detector distances for the same X-ray energy. After
      tomography, the sample was re-embedded into resin while retaining a dedicated
      sample orientation for subsequent sectioning and polishing, which was conducted
      until a previously defined spatial position was achieved. The protocol for resin
      embedding was developed to inhibit morphological changes during embedding. Giemsa
      staining was applied for better structural and morphological discrimination. Data
      from tomography and lightmicroscopy were exactly matched and finally compared to
      results from FIB/SEM imaging. Image detail was achieved at a single cell
      resolution. Image detail was achieved at a single cell resolution, which has been
      estimated to be 0.833MUm/voxel in the tomographic data. SR-MUCT with optimized
      phase contrast properties represents a method to investigate biological tissues
      in certain areas of interest, where true cellular resolution or enhanced
      volumetric imaging is needed. In this study, we demonstrate that this method can
      compete with conventional histology using light microscopy but even surpasses it
      due to the possibility of retrieving volumetric data.

PMID- 22633856
TI  - Exploiting an ancient signalling machinery to enjoy a nitrogen fixing symbiosis.
AB  - For almost a century now it has been speculated that a transfer of the largely
      legume-specific symbiosis with nitrogen fixing rhizobium would be profitable in
      agriculture [1,2]. Up to now such a step has not been achieved, despite intensive
      research in this era. Novel insights in the underlying signalling networks
      leading to intracellular accommodation of rhizobium as well as mycorrhizal fungi
      of the Glomeromycota order show extensive commonalities between both
      interactions. As mycorrhizae symbiosis can be established basically with most
      higher plant species it raises questions why is it only in a few taxonomic
      lineages that the underlying signalling network could be hijacked by rhizobium.
      Unravelling this will lead to insights that are essential to achieve an old
      dream.

PMID- 22633857
TI  - Life prediction of different commercial dental implants as influence by
      uncertainties in their fatigue material properties and loading conditions.
AB  - Probabilistic analyses allow the effect of uncertainty in system parameters to be
      determined. In the literature, many researchers have investigated static loading
      effects on dental implants. However, the intrinsic variability and uncertainty of
      most of the main problem parameters are not accounted for. The objective of this
      research was to apply a probabilistic computational approach to predict the
      fatigue life of three different commercial dental implants considering the
      variability and uncertainty in their fatigue material properties and loading
      conditions. For one of the commercial dental implants, the influence of its
      diameter in the fatigue life performance was also studied. This stochastic
      technique was based on the combination of a probabilistic finite element method
      (PFEM) and a cumulative damage approach known as B-model. After 6 million of
      loading cycles, local failure probabilities of 0.3, 0.4 and 0.91 were predicted
      for the Lifecore, Avinent and GMI implants, respectively (diameter of 3.75mm).
      The influence of the diameter for the GMI implant was studied and the results
      predicted a local failure probability of 0.91 and 0.1 for the 3.75mm and 5mm,
      respectively. In all cases the highest failure probability was located at the
      upper screw-threads. Therefore, the probabilistic methodology proposed herein may
      be a useful tool for performing a qualitative comparison between different
      commercial dental implants.

PMID- 22633858
TI  - Goethite-mediated transformation of bisphenol A.
AB  - Bisphenol A (BPA) is an environmental endocrine disruptor widely present in the
      soil and sedimentary environment. In this study, we investigated the oxidative
      transformation of BPA by commercial and laboratory synthetic goethite. Both
      goethite samples effectively induced the transformation of BPA. The commercial
      goethite exhibited higher oxidation power towards BPA than the synthetic one. The
      transformation of BPA by goethite was pH dependent, showing that acidic
      conditions accelerated the reaction in the pH range of 4.0-8.5. Co-solutes such
      as Fe(2+), Fe(3+), and humic acid exhibited moderate to slight inhibitory effects
      on the reaction because of the reducing sorption of BPA on goethite surface in
      the presence of these co-solutes. Transformation of BPA by goethite was
      accompanied by the release of Fe(2+). In addition, three reaction intermediates
      or products were identified and pathways of the transformation of BPA by goethite
      were proposed. Given that goethite is widespread in soils and sediments, results
      of this study suggest that goethite may play an important role in the abiotic
      attenuation of BPA in the natural environment.

PMID- 22633859
TI  - Cornmeal-induced resistance to ciprofloxacin and erythromycin in enterococci.
AB  - OBJECTIVE: To establish a model ecosystem to study the impact of cornmeal on the
      appearance and persistence of the erythromycin (ERY)- and ciprofloxacin (CIP)
      resistant phenotypes in waterborne enterococci. METHODS: After the model
      ecosystem was established, the system was divided into six dose groups, with the
      addition of 8, 4, 1, 0.25, 0.05, and 0 g L(-1) sterilized cornmeal. System mud
      samples were collected at 0, 1, 3, 7, 14, 30, 40, 61, and 130 d, and enterococci
      present in the mud samples were evaluated for their sensitivities to CIP and ERY.
      PCR was employed to detect genes such as gyrA and ermB. The gyrA gene was
      sequenced, and codons 83 and 87 were analyzed for mutations. RESULTS: (1) The
      addition of 0.05-8 g L(-1) cornmeal had an impact on CIP resistance. The higher
      the dose of cornmeal added, the larger the impact it generated. Furthermore, the
      earlier the emergence of CIP-resistant strains, the greater the incidence of drug
      resistance. The impact of cornmeal on resistance to ERY was less consistent, and
      the degree of the impact was not in proportion to the dose of cornmeal added. (2)
      There were no mutations at codons 83 and 87 in the gyrA genes from 102 strains
      isolated from the model ecosystem. The incidence of ermB-positive strains of ERY
      resistant enterococci (28 strains) was 78.6%, and the incidence of ermB-positive
      strains of ERY-sensitive enterococci (16 strains) was 0%. CONCLUSIONS: (1) Adding
      different doses of cornmeal can facilitate resistance to CIP and ERY in
      waterborne enterococci. In this study, the degree of resistance was related to
      the cornmeal dose. (2) In the model ecosystem, enterococcal CIP resistance was
      not caused by a gyrA gene mutation; however, in the vast majority of cases,
      resistance to ERY was related to the ermB resistance gene.

PMID- 22633860
TI  - Transport and attenuation of dissolved glyphosate and AMPA in a stormwater
      wetland.
AB  - Glyphosate is an herbicide used widely and increasingly since the early 1990s in
      production of many crops and in urban areas. However, knowledge on the transport
      of glyphosate and its degradation to aminomethylphosphonic acid (AMPA) in
      ecosystems receiving urban or agricultural runoff is lacking. Here we show that
      transport and attenuation of runoff-associated glyphosate and AMPA in a
      stormwater wetland differ and largely vary over time. Dissolved concentrations
      and loads of glyphosate and AMPA in a wetland receiving runoff from a vineyard
      catchment were assessed during three consecutive seasons of glyphosate use (March
      to June 2009, 2010 and 2011). The load removal of glyphosate and AMPA by the
      wetland gradually varied yearly from 75% to 99%. However, glyphosate and AMPA
      were not detected in the wetland sediment, which emphasises that sorption on the
      wetland vegetation, which increased over time, and biodegradation were prevailing
      attenuation processes. The relative load of AMPA as a percentage of total
      glyphosate increased in the wetland and ranged from 0% to 100%, which indicates
      the variability of glyphosate degradation via the AMPA pathway. Our results
      demonstrate that transport and degradation of glyphosate in stormwater wetlands
      can largely change over time, mainly depending on the characteristics of the
      runoff event and the wetland vegetation. We anticipate our results to be a
      starting point for considering degradation products of runoff-associated
      pesticides during their transfer in wetlands, in particular when using stormwater
      wetlands as a management practice targeting pesticide attenuation.

PMID- 22633861
TI  - Solar photocatalytic treatment of landfill leachate using a solid mineral by
      product as a catalyst.
AB  - The treatment of municipal solid waste landfill leachate in a pilot plant made up
      of solar compound parabolic collectors, using a solid industrial titanium by
      product (WTiO(2)) containing TiO(2) and Fe(III) as a photocatalyst, was
      investigated. In the study evidence was found showing that the degradation
      performed with WTiO(2) was mainly due to the Fe provided by this by-product,
      instead of TiO(2). However, although TiO(2) had very little effect by itself, a
      synergistic effect was observed between Fe and TiO(2). The application of
      WTiO(2), which produced coupled photo-Fenton and heterogeneous catalysis
      reactions, achieved a surprisingly high depuration level (86% of COD removal),
      higher than that reached by photo-Fenton using commercial FeSO(4) (43%) in the
      same conditions. After the oxidation process the biodegradability and toxicity of
      the landfill leachate were studied. The results showed that the leachate
      biodegradability was substantially increased, at least in the first stages of the
      process, and again that WTiO(2) was more efficient than FeSO(4) in terms of
      increasing biodegradability.

PMID- 22633862
TI  - Relevant parameters for assessing the environmental impact of some pyridinium,
      ammonium and pyrrolidinium based ionic liquids.
AB  - Several physico-chemical properties relevant to determine the environmental
      impact of ionic liquids - aqueous solubility, octanol/water partition
      coefficient, chromatographically derived lipophilicity and infinite dilution
      diffusion coefficients in water - were measured in ionic liquids based on
      pyridinium, ammonium and pyrrolidinium cations with
      bis(trifluoromethylsulfonyl)imide anions. The influence of the presence of
      hydroxyl or ester groups in the physico-chemical properties of these liquids was
      checked. It appeared that the presence of functional oxygenated moieties reduces
      the lipophilicity of ionic liquids and so decreases the risk of bioaccumulation
      in environment.

PMID- 22633863
TI  - Identification, cloning and characterisation of interleukin-1F5 (IL-36RN) in the
      chicken.
AB  - The human IL-1 family contains eleven genes encoded at three separate loci. Nine,
      including IL-36 receptor antagonist (IL-36RN), also known as IL-1F5, are present
      at a single locus on chromosome 2, whereas IL-18 and IL-33 lie on chromosomes 11
      and 9 respectively. There are currently only three known orthologues in the
      chicken - IL-1beta, IL-18 and IL-1RN - which are encoded on chromosomes 22, 24
      and unplaced, respectively. A novel chicken IL-1 family sequence representing IL
      36RN (IL-1F5) was initially identified from an expressed sequence tag (EST)
      library by its similarity to both chicken IL-1RN and chicken IL-1beta. Following
      isolation of the cDNA from the liver of an uninfected bird, a number of unique
      sequence features were identified. The predicted protein has a longer NH(2)
      terminus than the human protein; however, as in mammals, this region contains
      neither a prodomain nor a signal peptide. A putative nuclear export sequence is
      also apparent, yet a similar motif is absent in mammalian IL-36RN. Although chIL
      36RN exhibits low homology with its mammalian orthologues, it encodes a predicted
      beta-trefoil structure whose beta-strands are conserved with those of the mouse
      sequence. Unlike in mammals, chIL-36RN expression was constitutive in all tissues
      and cell subsets examined. In response to viral infection, expression was
      significantly downregulated in a line of birds which are susceptible to the
      virus. Chicken IL-36RN, like chIL-1RN, is not encoded at the chIL-1beta locus,
      further emphasising the genomic fragmentation of the large IL-1 gene cluster
      found in mammals. This suggests differential evolution of this cytokine family
      since the divergence of birds and mammals from a common ancestor, and underlines
      the difficulty of determining the full repertoire of chIL-1 family members.

PMID- 22633864
TI  - Reproducible vapor-time profiles using solid-phase microextraction with an
      externally sampled internal standard.
AB  - Determination of the dynamic nature of vapor/odor release has application in a
      wide variety of systems. This study applies automated solid-phase microextraction
      (SPME) utilizing an externally sampled internal standard (ESIS) to determine the
      vapor-time profile of odor delivery devices for three classes of explosive
      compounds. The profiles of delivery systems for target odorants 2,4
      dinitrotoluene (2,4-DNT), 2-ethyl-1-hexanol (2-EH), and triacetone triperoxide
      (TATP) as canine training aids were compared over a period of 70 h. Strategies
      for evaluating the vapor-time profile of components with widely differing
      volatility are considered. An approach to quantifying the vapor concentration is
      described. The differences in the vapor-time profiles are examined and
      suggestions for selecting the best representative odor delivery technique are
      outlined.

PMID- 22633865
TI  - Array capillary in-tube solid-phase microextraction: a rapid preparation
      technique for water samples.
AB  - A rapid sample preparation technique, namely array capillary in-tube solid-phase
      microextraction (ACIT-SPME) for direct extraction of organic pollutants from
      water samples, was developed and evaluated. The ACIT-SPME cartridge consisted of
      a bundle of glass capillary tubes of 0.5 mm I.D. * 30mm contained inside a quartz
      liner of 4 mm I.D. The high ratio of cross-section area of channel-to-wall
      allowed water sample flow through the cartridge just under gravity. Both the
      internal/external surfaces of the array capillary tubing were coated with
      extraction phase of 2-5 MUm in thickness, which provided large extraction surface
      area up to 30 cm2 for a cartridge containing 19 glass capillaries. The large
      surface area and thin extraction phase improved greatly both the mass transfer
      process of extraction and the thermo desorption process, leading to fast
      extraction and fast desorption. The extracted analytes were thermally desorbed in
      a homemade thermal desorption unit (TDU), which was coupled to a gas
      chromatograph equipped with a flame ionization detector for analysis. By using
      polydimethylsiloxane (PDMS) as the extraction phase and polycyclic aromatic
      hydrocarbons (PAHs) as the model analytes, the performance of the ACIT-SPME
      cartridge was systematically investigated. The extraction time was 2 min for 350
      mL of water sample, and detection limits were between 0.8 and 1.7 ng/L with
      deviation of 2.8-9.7% RSD. Relative recoveries of analytes for real water samples
      were between 65.0% and 116%. The extraction time can even be further shortened to
      10s for 250 mL sample by applying vacuum at the outlet of the cartridge, with
      detection limits of 2.2-5.3 ng/L and deviation of 4.0-12% RSD.

PMID- 22633866
TI  - Analysis of 18 perfluorinated compounds in river waters: comparison of high
      performance liquid chromatography-tandem mass spectrometry, ultra-high
      performance liquid chromatography-tandem mass spectrometry and capillary liquid
      chromatography-mass spectrometry.
AB  - In this work, the performance of ultra-high-performance liquid chromatography
      tandem mass spectrometry (UHPLC-MS/MS) and capillary liquid chromatography-mass
      spectrometry (CLC-MS) has been studied for the analysis of eighteen
      perfluorinated compounds in water samples. UHPLC-MS/MS and CLC-MS analysis were
      carried out using a Zorbax C-18 column (50 mm * 2.1 mm, 1.8 MUm) and a Zorbax SB
      C18 column (150 mm * 0.5 mm, 3.5 MUm), respectively, in gradient elution mode
      with a mobile phase of ammonium formate and methanol. Both techniques were
      compared with conventional LC-MS/MS in terms of speed, sensitivity, selectivity
      and resolution. Water samples were extracted by solid phase extraction (SPE).
      Mean absolute recoveries at two concentration levels, 6 and 60 ng L-1, calculated
      from the eighteen compounds were: 77 +/- 12(s) and 82 +/- 12(s), respectively.
      Relative standard deviation (RSD) was lower than 16% for each perfluorinated
      compound. The results obtained showed that UHPLC-MS/MS and CLC-MS allow the
      determination of perfluorinated compounds in water samples with satisfactory
      sensitivity and resolution and reduced analysis time. Therefore, both techniques
      were employed for the analysis of water samples to determine the target analytes
      at low concentration levels and with lower analysis times than using HPLC-MS/MS.
      Similar statistical values were obtained from both techniques at 95% confidence
      level. Several compounds have been detected, but perfluorooctanoic acid (PFOA)
      (171 ng L-1 and 148 ng L-1 by UHPLC-MS/MS and CLC-MS, respectively) showed the
      highest concentration.

PMID- 22633867
TI  - School-located influenza immunization programs: factors important to parents and
      students.
AB  - PURPOSE: To describe both parent and student perspectives on the importance of
      various programmatic factors when deciding to participate in a school-located
      immunizations program (SLIP) for influenza vaccine. METHODS: Questionnaires were
      distributed to middle- and high-school students and their parents; the document
      assessed demographic data, influenza vaccination history, and the importance of
      various factors in their decision to participate in a potential SLIP for
      influenza vaccine. Factor analysis created six primary factors of importance
      related to programming: (1) safety/trust; (2) outbreaks (representing imminent
      threat of disease, an environmental factor associated with program timing); (3)
      issues of site implementation; (4) public health benefits; (5) record-keeping;
      (6) medical/emotional support. RESULTS: Participants included 621 students and
      579 parents; 566 student/parent dyads were included. Most respondents were
      female, felt it is important to be immunized against the flu, and received the
      influenza vaccine in the past. Fewer than 50% had received the intranasal
      vaccine. More parents (67%) than students (46%) expressed a general willingness
      to consent to utilizing a SLIP. The programmatic factors associated with public
      health were second only to safety/trust factors as the most important to parents
      and students when considering participation in a SLIP. Demographic variables were
      found to be associated with the importance ratings of program factors associated
      with participation in a SLIP. CONCLUSIONS: When considering possible
      participation in SLIPs, parents and students consider programmatic factors
      associated with safety/trust and public health benefits to be of the greatest
      importance. Further study will be needed to develop effective and culturally
      sensitive messaging that targets and emphasizes these factors to potentially
      increase participation in SLIPS.

PMID- 22633868
TI  - Host immune response to A(H1N1)pdm09 vaccination and infection: a one-year
      prospective study on six cohorts of subjects.
AB  - BACKGROUND: The long-term immunogenicity after novel vaccine against A(H1N1)pdm09
      administration or natural infection has not been well investigated. METHODS: Six
      cohorts of subjects were followed up for over one year: one-dose A(H1N1)pdm09
      vaccine recipient, A(H1N1)pdm09-seasonal trivalent vaccine recipients in
      different orders, confirmed A(H1N1)pdm09 patients without vaccination, with
      previous A(H1N1)pdm09 or seasonal influenza vaccination. Peripheral blood
      mononuclear cells and sera samples were collected at baseline and month 1, 2, 3,
      7 and 14 after vaccination (infection). The immunogenicity was determined by
      hemagglutination-inhibition (HI) and B cell enzyme-linked immunospot (ELISPOT)
      assays. RESULTS: Single dose of A(H1N1)pdm09 vaccine elicited antibody titer of
      greater than 1:40 in 40% adults for 1 year and mean live of this adequate
      antibody was determined as 8.35 months. In contrast, responses after natural
      infections had lower peaking level and a relatively longer antibody duration,
      with estimated mean lives of 11.8 months. Pre-vaccination with the seasonal flu
      vaccine led to a significant reduction in HI titer to A(H1N1)pdm09 one month
      after vaccination, while pre-vaccination with A(H1N1)pdm09 had no effect on
      seasonal influenza vaccination. Seasonal flu vaccination followed by A(H1N1)pdm09
      infection elicited boosting effect on antibody response against A(H1N1)pdm09. A
      similar memory B cell response was elicited from both vaccination and infection
      by ELISPOT assay. CONCLUSIONS: The long-term decay of immunity for A(H1N1)pdm09
      vaccine and natural infection indicates the need of revaccination after the host
      lose protection acquired from either vaccination or infection. Prior infection,
      rather than the pre-vaccination with seasonal influenza could act on the host
      immunity to elicit boosting effect on the A(H1N1)pdm09.

PMID- 22633869
TI  - Development of a scaled-down aerobic fermentation model for scale-up in
      recombinant protein vaccine manufacturing.
AB  - A simple approach to the development of an aerobic scaled-down fermentation model
      is presented to obtain more consistent process performance during the scale-up of
      recombinant protein manufacture. Using a constant volumetric oxygen mass transfer
      coefficient (k(L)a) for the criterion of a scale-down process, the scaled-down
      model can be "tuned" to match the k(L)a of any larger-scale target by varying the
      impeller rotational speed. This approach is demonstrated for a protein vaccine
      candidate expressed in recombinant Escherichia coli, where process performance is
      shown to be consistent among 2-L, 20-L, and 200-L scales. An empirical
      correlation for k(L)a has also been employed to extrapolate to larger
      manufacturing scales.

PMID- 22633870
TI  - Antigen adsorbed surface modified poly-E-caprolactone microspheres stimulates
      both adaptive and innate immune response in fish.
AB  - Surface modified poly-E-caprolactone microspheres as an antigen carrier was
      explored in a fish model. Outer membrane vesicles of Edwardsiella tarda adsorbed
      on to surface modified poly-E-caprolactone microspheres with chitosan and
      alginate induces both innate and adaptive immune responses which persist up to 63
      days of post immunization through parenteral immunization unlike that of free and
      FIA adjuvented antigens. These results highlight the role of these microspheres
      as an adjuvant/antigen carrier in fish.

PMID- 22633871
TI  - Skin-tightening effect of fractional lasers: comparison of non-ablative and
      ablative fractional lasers in animal models.
AB  - This experimental study was performed to demonstrate the effects of non-ablative
      fractional laser (NAFL) and ablative fractional laser (AFL). Twenty male Sprague
      Dawley rats were used for the study. Three 2*2-cm-sized squares were tattooed on
      the abdomen of the animals. Each tattooed square was used for NAFL, AFL and
      control experiments. The NAFL and AFL treatment were performed with the same
      total energy of 12,000 mJ cm(-2). The laser treatments consisted of four
      sessions, with an interval of 3 weeks between sessions. The areas of tattooed
      skin were serially measured, and skin samples were obtained for histologic
      examination after 4 months of treatment. NAFL did not cause immediate skin
      shrinkage, but the size of the NAFL-treated skin was reduced by 4.3% after 4
      months. In contrast, AFL caused immediate skin shrinkage (11.5% reduction), and
      the size was maintained at 9% reduction after 4 months. In histologic
      examination, the dermal collagen was arranged flat and parallel to the skin
      surface in the upper dermis, and regenerated collagen fibres were clearly noticed
      in both NAFL-and AFL-treated skin samples. Immunohistochemical stains showed well
      regenerated type I and III collagen fibres. Western blot analysis of skin samples
      showed that type I/III collagen ratio was not significantly changed after
      fractional laser treatment. Electron microscopic studies aimed to evaluate the
      long-term micro-architecture of the collagen fibrils. AFL treatment reduced D
      band periodicity by 5.2% and fibril diameter by 14.8%, although there was no
      statistically significant difference (p>0.05). Fractional laser treatment shrinks
      the skin surface area and regenerates collagen. The AFL treatment showed more
      profound skin changes than NAFL.

PMID- 22633872
TI  - Vascularised fat flaps lose 44% of their weight 24 weeks after transplantation.
AB  - BACKGROUND: Microsurgical transfer of the vascularised fat flaps has become a
      well-established method for soft-tissue augmentation because it has been believed
      to provide the restoration of symmetry without atrophy. Yet little has been
      reported on the long-term fate of the vascularised fat flaps. The purpose of this
      study was to evaluate the postoperative changes that occur in the vascularised
      fat flaps after transplantation. METHODS: The superficial epigastric fat flaps
      based on the superficial inferior epigastric vessels in rats were used for this
      study. Postoperative changes were analysed by comparing pre- and postoperative
      weight, histological examination and fluorescent angiography. RESULTS: The weight
      of vascularised fat flaps was 56+/-18% of the original weight (corrected for body
      weight gain) 24 weeks after transplantation. In histological examinations, the
      vascularised fat flaps had almost normal appearances throughout the experimental
      period. Apoptosis of adipocytes was detected in the vascularised fat flaps using
      terminal deoxynucleotidyl transferase (TdT)-mediated deoxy-uridine triphosphate
      (dUTP)-biotin nick end-labelling (TUNEL) method during the first 4 weeks after
      transplantation. CONCLUSIONS: The vascularised fat flaps reduced in weight by
      about 44% over a period of 24 weeks after transplantation. Apoptosis may partly
      explain the weight loss.

PMID- 22633873
TI  - Paternal depression and risk for child neglect in father-involved families of
      young children.
AB  - OBJECTIVE: To examine the association of paternal depression with risk for
      parental neglect of young children. STUDY DESIGN: The sample was derived from a
      birth cohort study of 1,089 families in which both biological parents resided in
      the home when the target child was 3- and 5-years old. Prospective analyses
      examined the contribution of paternal and maternal parenting risks (e.g.,
      depression, alcohol use, and parenting stress) to the incidence of neglect of the
      target child. Models accounted for a comprehensive set of factors associated with
      parental child neglect in 2-parent families, including quality of the parental
      relationship, household economic conditions, and paternal demographic
      characteristics. RESULTS: Approximately 12% of families reported at least 1
      instance of neglect; 10% of fathers were depressed when their child was 3-years
      old. Rates of paternal and maternal depression were twice as high in families in
      which child neglect was present. Paternal depression when a child was 3-years old
      was associated with increased odds of child neglect at age 5 [adjusted odds
      ratio: 1.94 (95% confidence interval: 1.18-3.19); P<.01]. Father-related risks
      for neglect remained statistically significant after accounting for strong,
      significant effects of maternal parenting risks, including maternal depression,
      and household economic hardship. Paternal parenting stress was also associated
      with heightened risk for neglect, although only at the level of marginal
      significance after accounting for maternal parenting risks [adjusted odds ratio:
      1.40 (95% confidence interval: 0.97-2.04); P=.075]. CONCLUSIONS: Screening
      fathers for parenting risks such as depression during well-baby visits and social
      work intervention to facilitate fathers' help-seeking behaviors related to
      treatment of depression may help to prevent and reduce risk of neglect.

PMID- 22633874
TI  - Identification and characterization of FHL3 as a novel angiogenin-binding
      partner.
AB  - Angiogenin (Ang) is known to induce cell proliferation and inhibit apoptosis by
      cellular signaling pathways and by direct nuclear functions of Ang, but the
      mechanism of action for Ang is not yet clear. The aim of present study was to
      identify novel binding partner of Ang and to explore the underlying mechanism.
      With the use of yeast two-hybrid screening system, Ang was used as the bait to
      screen human fetal hepatic cDNA library for interacting proteins. Four and a half
      LIM domains 3 (FHL3) was identified as a novel Ang binding partner. The
      interaction between Ang and the full length FHL3 was further confirmed by yeast
      two-hybrid assay, co-immunoprecipitation and GST pull-down assays. Furthermore,
      FHL3 was required for Ang-mediated HeLa cell proliferation and nuclear
      translocation of Ang. These findings suggest that the interaction between Ang and
      FHL3 may provide some clues to the mechanisms of Ang-regulated cell growth and
      apoptosis.

PMID- 22633875
TI  - Changes in hair morphology as a biomarker in gene expression-targeted isoflavone
      therapy for Sanfilippo disease.
AB  - Lack of unequivocal markers for assessment of therapeutic effects of treatment
      procedures is a common problem, but it is especially pronounced in genetic
      diseases. One of them is Sanfilippo disease (mucopolysaccharidosis type III, or
      MPS III). Changes in hair morphology have already been reported as one of
      characteristic and easily detected symptoms of this disease and other
      mucopolysaccharidoses. This feature has been used previously to monitor efficacy
      of gene expression-targeted isoflavone therapy (GET IT) in pilot clinical studies
      performed with low number of patients. Here, we studied changes in hair
      morphology, observed by using scanning electron microscopy, in 35 patients
      subjected to GET IT for one year at doses of 5 and 15 mg/kg/day. We have observed
      statistically significant correction of hair morphology in both groups of
      patients, corroborating results of earlier studies with low number of patients
      that suggested easily observable improvement in this parameter during different
      therapies of MPS. Since the improvement was evident in both previous reports and
      this study, we propose that analysis of hair morphology may be considered as a
      non-invasive method in monitoring effects of treatment on somatic symptoms of
      Sanfilippo disease patients.

PMID- 22633876
TI  - A quadruplex tetra-primer ARMS-PCR method for the simultaneous detection of TP53
      Arg72Pro, IVS3 16bp Del/Ins and IVS6+62A>G, and NQO1 C609T polymorphisms.
AB  - The apoptotic pathway has been shown to be crucial in the development of cancers
      in addition to a variety of neurodegenerative disorders. The tumor suppressor
      gene (TP53) encodes p53, the central protein in the apoptotic pathway. The
      NAD(P)H:quinone oxidoreductase 1, which is encoded by the NQO1 gene and, plays a
      direct role in apoptosis in addition to its recently discovered role as a
      regulator for p53. Three most commonly studied polymorphisms that were shown to
      affect the biochemical functions of p53 protein are the exon 4 Arg72pro, Intron 3
      16bp Del/Ins, and Intron 6 A>G polymorphisms. The exon 6 C609T polymorphism was
      shown to significantly affect NQO1 enzymatic activity. The currently used methods
      for the separate detection of the four polymorphisms are either slow and
      laborious or extremely expensive. In this paper, a new highly optimized method
      for the simultaneous detection of the four polymorphisms is described. The
      proposed method utilizes 13 primers in a single PCR reaction to detect the four
      polymorphisms simultaneously based on the principle of tetra-primer ARMS-PCR
      (also known as PCR-CTPP). The proposed method offers extremely fast, economical,
      and simple detection. The proposed method was successfully applied to a sample of
      the Syrian population (n=144), where we found a unique distribution for TP53
      polymorphisms that differed from the major ethnic groups. The proposed method is
      the first to simultaneously detect four polymorphisms including 3 SNPs in a
      single PCR reaction based on tetra-primer ARMS-PCR or PCR-CTPP, and can serve as
      an invaluable tool for the investigation of TP53 haplotypes and the combined
      effects of the TP53 and NQO1 genes with respect to apoptosis and susceptibility
      for various types of cancers and neurodegenerative disorders.

PMID- 22633877
TI  - Genome-wide comparative analysis of simple sequence coding repeats among 25
      insect species.
AB  - We present a detailed genome-scale comparative analysis of simple sequence
      repeats within protein coding regions among 25 insect genomes. The repetitive
      sequences in the coding regions primarily represented single codon repeats and
      codon pair repeats. The CAG triplet is highly repetitive in the coding regions of
      insect genomes. It is frequently paired with the synonymous codon CAA to code for
      polyglutamine repeats. The codon pairs that are least repetitive code for
      polyalanine repeats. The frequency of hexanucleotide and dinucleotide motifs of
      codon pair repeats is significantly (p<0.001) different in the Drosophila species
      compared to the non-Drosophila species. However, the frequency of synonymous and
      non-synonymous codon pair repeats varies in a correlated manner (r(2)=0.79) among
      all the species. Results further show that perfect and imperfect repeats have
      significant association with the trinucleotide and hexanucleotide coding repeats
      in most of these insects. However, only select species show significant
      association between the numbers of perfect/imperfect hexamers and repeat coding
      for single amino acid/amino acid pair runs. Our data further suggests that genes
      containing simple sequence coding repeats may be under negative selection as they
      tend to be poorly conserved across species. The sequences of coding repeats of
      orthologous genes vary according to the known phylogeny among the species. In
      conclusion, the study shows that simple sequence coding repeats are important
      features of genome diversity among insects.

PMID- 22633878
TI  - Natural zeolite reactivity towards ozone: the role of compensating cations.
AB  - Among indoor pollutants, ozone is recognised to pose a threat to human health.
      Recently, low cost natural zeolites have been applied as alternative materials
      for ozone abatement. In this work, the effect of compensating cation content of
      natural zeolite on ozone removal is studied. A Chilean natural zeolite is used
      here as starting material. The amount of compensating cations in the zeolite
      framework was modified by ion exchange using an ammonium sulphate solution (0.1
      mol L(-1)). Characterisation of natural and modified zeolites were performed by X
      ray powder diffraction (XRD), nitrogen adsorption at 77K, elemental analysis, X
      ray fluorescence (XRF), thermogravimetric analysis coupled with mass spectroscopy
      (TGA-MS), and temperature-programmed desorption of ammonia (NH(3)-TPD). Ozone
      adsorption and/or decomposition on natural and modified zeolites were studied by
      diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Results
      show that the zeolite compensating cation content affects ozone interaction with
      zeolite active sites. Ammonium ion-exchange treatments followed by thermal out
      gassing at 823 K, reduces ozone diffusion resistance inside the zeolite
      framework, increasing ozone abatement on zeolite surface active sites. Weak and
      strong Lewis acid sites of zeolite surface are identified here as the main active
      sites responsible of ozone removal.

PMID- 22633879
TI  - Accelerated carbonation of steelmaking slags in a high-gravity rotating packed
      bed.
AB  - Carbon dioxide (CO(2)) sequestration using the accelerated carbonation of basic
      oxygen furnace (BOF) slag in a high-gravity rotating packed bed (RPB) under
      various operational conditions was investigated. The effects of reaction time,
      reaction temperature, rotation speed and slurry flow rate on the CO(2)
      sequestration process were evaluated. The samples of reacted slurry were analyzed
      quantitatively using thermogravimetric analysis (TGA) and atomic absorption
      spectrometry (AAS) and qualitatively using X-ray diffraction (XRD), scanning
      electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX), and
      transmission electron microscopy (TEM). The sequestration experiments were
      performed at a liquid-to-solid ratio of 20:1 with a flow rate of 2.5 L min(-1) of
      a pure CO(2) stream under atmospheric temperature and pressure. The results show
      that a maximum conversion of BOF slag was 93.5% at a reaction time of 30 min and
      a rotation speed of 750 rpm at 65 degrees C. The experimental data were utilized
      to determine the rate-limiting mechanism based on the shrinking core model (SCM),
      which was validated by the observations of SEM and TEM. Accelerated carbonation
      in a RPB was confirmed to be a viable method due to its higher mass-transfer
      rate.

PMID- 22633880
TI  - Factors affecting the level and pattern of polycyclic aromatic hydrocarbons
      (PAHs) at Gosan, Korea during a dust period.
AB  - Polycyclic aromatic hydrocarbons (PAHs) in both gas and total suspended particles
      were measured at Gosan, Jeju Island in Korea, a remote background site, for 15
      days (March 29-April 12, 2002). During the sampling period, a severe three-day
      Asian dust (AD) event originating from Mongolia and northern China was observed
      throughout the Korean Peninsula and Jeju Island. In addition, pollution (PO) and
      normal (NO) periods were also identified based on the levels of anthropogenic
      pollutants. Despite a large difference of PM(10) concentrations between the AD
      and PO periods, the levels of particulate PAHs in both periods were comparable
      (2.7+/-1.0 and 2.4+/-0.5 ng m(-3), respectively) since they were determined by
      the concentration of anthropogenic PM(2.5) transported from industrial areas of
      China. In the AD period, the level of gaseous PAHs, which were mostly from local
      sources, was the lowest due to strong winds; the gas/particle partitioning was
      close to equilibrium as the effect of long-range transport was manifested. The
      results of backward air trajectories, correlation analysis, and diagnostic ratios
      show that long-range transport of particulate PAHs produced by coal/biomass
      burning in China could strongly affect the levels and patterns of PAHs at Gosan,
      Korea.

PMID- 22633881
TI  - Lab-scale simulation of the fate and transport of nano zero-valent iron in
      subsurface environments: aggregation, sedimentation, and contaminant desorption.
AB  - Heavy metal removal using nano zero-valent iron (NZVI) has drawn growing
      attention due to the ease of application and high removal efficiency. However,
      uncertainties regarding its fate and transport in subsurface environments have
      raised concerns that require further exploration. In this study, aggregation,
      sedimentation, and Cr/As desorption of three types of NZVIs were investigated
      under various conditions. It was found that the aggregation behavior of the NZVIs
      differed from one another in regard to reaction time and ionic strength,
      associated with the respective critical size for sedimentation. Sedimentation of
      NZVIs was positively related to the concentrations and average particle sizes.
      The sedimentation kinetics of NZVI followed two concomitant processes, i.e., (1)
      direct sedimentation of larger particles, and (2) initial aggregation and then
      sedimentation of smaller particles. When loaded with Cr/As, NZVIs tended to
      deposit faster, possibly due to the precipitation of Cr/As onto the nanoparticle
      surfaces resulting in larger particle sizes. Moreover, desorption of Cr/As from
      Cr/As loaded NZVIs was detected in the presence of typical groundwater ions, as
      well as natural organic matter, and poses a potential risk to the subsurface
      environment. The desorption of Cr was linearly related to the release of iron
      ions, while As desorption was mitigated when the immobilization of Cr increased.

PMID- 22633882
TI  - A multimodal location and routing model for hazardous materials transportation.
AB  - The recent US Commodity Flow Survey data suggest that transporting hazardous
      materials (HAZMAT) often involves multiple modes, especially for long-distance
      transportation. However, not much research has been conducted on HAZMAT location
      and routing on a multimodal transportation network. Most existing HAZMAT location
      and routing studies focus exclusively on single mode (either highways or
      railways). Motivated by the lack of research on multimodal HAZMAT location and
      routing and the fact that there is an increasing demand for it, this research
      proposes a multimodal HAZMAT model that simultaneously optimizes the locations of
      transfer yards and transportation routes. The developed model is applied to two
      case studies of different network sizes to demonstrate its applicability. The
      results are analyzed and suggestions for future research are provided.

PMID- 22633883
TI  - Mechanism insights into enhanced Cr(VI) removal using nanoscale zerovalent iron
      supported on the pillared bentonite by macroscopic and spectroscopic studies.
AB  - NZVI was supported on a pillared bentonite (Al-bent) to enhance the reactivity of
      NZVI and prevent its aggregation. The performance and mechanisms of the combined
      NZVI/Al-bent on removing hexavalent chromium (Cr(VI)) was investigated by batch
      and XAFS experiments. The batch investigations indicated that Cr(VI) could be
      almost completely removed by NZVI/Al-bent after 120 min. The efficiency was not
      only much higher than that by NZVI (63.0%), but also superior to the sum of NZVI
      reduction and Al-bent adsorption (12.4%). Besides, NZVI/Al-bent exhibited good
      stability and reusability, and Al-bent could reduce the amount of iron ions
      released into the solution. XANES results provided evidence that NZVI/Al-bent
      could reduce Cr(VI) entirely into Cr(III), while NZVI reduced Cr(VI) partly into
      Cr(III) with a trace of Cr(VI) adsorbed on the corrosion products. The structure
      of Cr(VI)-treated NZVI/Al-bent determined with EXAFS revealed the formation of Cr
      Al/Si bond, suggesting that some insoluble Cr(III) species might be transferred
      to the surface of Al-bent, therefore the precipitates on iron surface could be
      greatly reduced. The results demonstrated that Al-bent plays a significant role
      in enhanced reactivity and stability of NZVI, and may shed new light on design
      and fabrication of supported NZVI for environmental remediation.

PMID- 22633884
TI  - A comprehensive risk assessment framework for offsite transportation of
      inflammable hazardous waste.
AB  - A framework for risk assessment due to offsite transportation of hazardous wastes
      is designed based on the type of event that can be triggered from an accident of
      a hazardous waste carrier. The objective of this study is to design a framework
      for computing the risk to population associated with offsite transportation of
      inflammable and volatile wastes. The framework is based on traditional definition
      of risk and is designed for conditions where accident databases are not
      available. The probability based variable in risk assessment framework is
      substituted by a composite accident index proposed in this study. The framework
      computes the impacts due to a volatile cloud explosion based on TNO Multi-energy
      model. The methodology also estimates the vulnerable population in terms of
      disability adjusted life years (DALY) which takes into consideration the
      demographic profile of the population and the degree of injury on mortality and
      morbidity sustained. The methodology is illustrated using a case study of a
      pharmaceutical industry in the Kolkata metropolitan area.

PMID- 22633885
TI  - A structured approach to documenting a search strategy for publication: a 12 step
      guideline for authors.
AB  - AIM: This paper describes a structured approach for documenting a search
      strategy, prior to the scholarly critique and review of the retrieved literature.
      BACKGROUND AND CONTEXT: There has been a shift in publication expectations when
      it comes to the presentation of a literature review, from the more traditional
      narrative review to a more systematic approach, following a specific framework.
      METHODS: This paper presents a 12 step framework for documenting the search
      strategy prior to undertaking a critique and synthesis of the retrieved
      literature. The authors provide a worked example about potential sources of cross
      contamination including hospital bath basins and soap and water bathing.
      DISCUSSION: An overview of the 12 step framework is presented. This includes step
      by-step instructions on how to conduct and write a search strategy for a
      literature review. A number of resources available for creating reviews and
      critiquing reviews are referenced, but these are not exclusive. CONCLUSION:
      Reviews can be an important and valuable contribution when undertaken well,
      providing the reader with evidence of a clear structure. This paper provides a 12
      step framework that will be of benefit to students, educationalists, and
      researchers required to embark on a review.

PMID- 22633886
TI  - Identifying gnostic predictors of the vaccine response.
AB  - Molecular predictors of the response to vaccination could transform vaccine
      development. They would allow larger numbers of vaccine candidates to be rapidly
      screened, shortening the development time for new vaccines. Gene-expression based
      predictors of vaccine response have shown early promise. However, a limitation of
      gene-expression based predictors is that they often fail to reveal the
      mechanistic basis of their ability to classify response. Linking predictive
      signatures to the function of their component genes would advance basic
      understanding of vaccine immunity and also improve the robustness of vaccine
      prediction. New analytic tools now allow more biological meaning to be extracted
      from predictive signatures. Functional genomic approaches to perturb gene
      expression in mammalian cells permit the function of predictive genes to be
      surveyed in highly parallel experiments. The challenge for vaccinologists is
      therefore to use these tools to embed mechanistic insights into predictors of
      vaccine response.

PMID- 22633887
TI  - NMR spectroscopy of G-quadruplexes.
AB  - G-rich DNA and RNA sequences can form four-stranded structures called G
      quadruplexes. Such structures have gained significant interest in the past decade
      with increasing evidence of their biological role. G-quadruplex structures can be
      polymorphic and dynamic. NMR spectroscopy has played an important role in G
      quadruplex research. Here we review on the application of NMR techniques to study
      structure, dynamics and interaction of G-quadruplexes.

PMID- 22633888
TI  - Thermoluminescence in medical dosimetry.
AB  - Thermoluminescence dosimetry (TLD) is applied worldwide for personal and medical
      dosimetry. TLD method has resulted in many interesting findings in medicine as TL
      dosimeters have many relevant advantages such as high sensitivity, small physical
      size, tissue equivalence, etc. The main characteristics of various TL materials
      used in radiation measurements and their practical consequences are overviewed:
      well defined TL glow curve, batch homogeneity, signal stability after
      irradiation, precision and accuracy, response with dose, and influence of energy.
      In this paper a brief summary of the advances in the application of thermally
      stimulated luminescence (TSL) to dosimetry in radiation therapy application is
      presented.

PMID- 22633889
TI  - How the insect pathogen bacteria Bacillus thuringiensis and
      Xenorhabdus/Photorhabdus occupy their hosts.
AB  - Insects are the largest group of animals on earth. Like mammals, virus, fungi,
      bacteria and parasites infect them. Several tissue barriers and defense
      mechanisms are common for vertebrates and invertebrates. Therefore some insects,
      notably the fly Drosophila and the caterpillar Galleria mellonella, have been
      used as models to study host-pathogen interactions for several insect and mammal
      pathogens. They are excellent tools to identify pathogen determinants and host
      tissue cell responses. We focus here on the comparison of effectors used by two
      different groups of bacterial insect pathogens to accomplish the infection
      process in their lepidopteran larval host: Bacillus thuringiensis and the
      nematode-associated bacteria, Photorhabdus and Xenorhabdus. The comparison
      reveals similarities in function and expression profiles for some genes, which
      suggest that such factors are conserved during evolution in order to attack the
      tissue encountered during the infection process.

PMID- 22633890
TI  - Single-center comparison of complications in laparoscopic and percutaneous
      radiofrequency ablation with ultrasound guidance for renal tumors.
AB  - OBJECTIVE: To report on postoperative complications associated with laparoscopic
      radiofrequency ablation (LRFA) and percutaneous radiofrequency ablation (PRFA) in
      a single-center experience. METHODS: We conducted a retrospective review of
      medical records for patients undergoing LRFA or PRFA between February 2006 and
      March 2010 at our center. Demographics, radiographic variables, and complication
      rates were compared between the 2 groups. Risk factors for postoperative
      complications after operation were analyzed with multivariate logistic
      regression. RESULTS: Of a total 191 patients included in this study, 132
      underwent LRFA and 59 underwent PRFA. There were no significant differences
      between the 2 groups with respect to age, gender, biopsy data, American Society
      of Anesthesiologists classification, body mass index, single kidney, tumor size,
      tumor number, glomerular filtration rate, follow-up, or RENAL nephrometry score.
      We observed complications in 16 LRFA procedures (12.1%) and 10 PRFA procedures
      (16.9%) (P = .369). There was no difference in the distribution of the
      complications between LRFA and PRFA groups. The complication (grades 1 and 2)
      rate in the LRFA group (7.6%) was not significantly different from that in the
      PRFA group (10.2%) (P = .550). The complication (grade 3a) rate in the LRFA group
      (4.5%) was not significantly different from that in the PRFA group (6.8%) (P =
      .522). A multivariate analysis disclosed that extra ablation time was the only
      predictor of postoperative complications. CONCLUSION: Significantly more anterior
      tumors were approached laparoscopically, and significantly more posterior tumors
      were approached percutaneously. Complication rate was not significantly different
      between LRFA and PRFA. Extra ablation time was a significant risk factor
      associated with postoperative complications.

PMID- 22633892
TI  - Editorial comment.

PMID- 22633894
TI  - Quality assessment of electroencephalography obtained from a "dry electrode"
      system.
AB  - This study examines the difference in application times for routine
      electroencephalography (EEG) utilizing traditional electrodes and a "dry
      electrode" headset. The primary outcome measure was the time to interpretable EEG
      (TIE). A secondary outcome measure of recording quality and interpretability was
      obtained from EEG sample review by two blinded clinical neurophysiologists. With
      EEG samples obtained from 10 subjects, the average TIE for the "dry electrode"
      system was 139s, and for the conventional recording 873s (p<0.001). The results
      support the hypothesis that such a "dry electrode" system can be applied with
      more than an 80% reduction in the TIE while still obtaining interpretable EEG.

PMID- 22633893
TI  - Local or spinal anesthesia in subinguinal varicocelectomy: a prospective
      randomized trial.
AB  - OBJECTIVE: To determine whether local anesthesia (LA) is an acceptable
      alternative to spinal anesthesia (SA) for varicocelectomy. METHODS: A total of 60
      men with varicocele were included in the present study. The evaluation of pain
      during and after surgery was determined using the visual analog scale. The
      secondary outcome measures of the present study were the interval to the first
      postoperative analgesic requirement, total analgesic consumption, and the
      incidence of side effects. RESULTS: The mean postoperative visual analog scale
      score was 2.56 +/- 1.85 for the SA group and 2.77 +/- 1.94 for the LA group (P =
      .659). Patients in the SA group experienced significantly less pain during
      surgery than those in the LA group (P = .017). However, the pain scores between
      the 2 groups did not differ significantly at 2, 4, 6, 8, 12, or 24 hours after
      surgery. In addition, a positive correlation was found between the duration of
      symptoms and the visual analog scale score at 24 hours postoperatively. The mean
      dosage of injected diclofenac was 46.5 +/- 23.3 mg and 32 +/- 28.15 mg in the SA
      and LA groups, respectively (P = .018). The SA group developed more postoperative
      complications, such as urinary retention, postspinal backache, headache,
      hypotension, and delayed mobilization, in the postoperative period. CONCLUSION:
      LA is an effective, reliable, reproducible, simple, and safe alternative
      anesthetic method for subinguinal varicocelectomy.

PMID- 22633895
TI  - Dissociation of CA3 pyramidal cells with attached, functional, identified mossy
      fiber and interneuronal boutons for studying glutamatergic and GABAergic synaptic
      transmission.
AB  - Pyramidal cells of CA3 area receive glutamatergic signals from the mossy fibers
      (MFs), perforant path and collaterals of other pyramidal cells, as well as
      GABAergic inputs from interneurons. In hippocampal slices, an extracellular
      stimulation electrode is often used to activate the MFs, with the disadvantage of
      possibly activating fibers other than MFs. We set-up a preparation that allows
      the analysis of the glutamatergic input from identified, giant MF boutons as well
      as of GABAergic inputs from boutons of interneurons on single CA3 pyramidal
      cells. Mossy fiber boutons were labeled by exposing hippocampal slices to a zinc
      reactive fluorescent dye, or by injecting a fluorescent dye in the granule cell
      layer and allowing its transport along the MFs to their terminals in CA3 area.
      After conducting an enzyme-free, mechanical dissociation of CA3 area, we obtained
      pyramidal cells containing fluorescent, giant MF boutons attached to their apical
      dendrites, as well as boutons of interneuronal origin. Whole cell recordings were
      then performed, whereby synaptic responses could be evoked by selective
      stimulation of the identified boutons. The synaptic currents evoked by
      stimulation of MF boutons, unlike those evoked by stimulation of interneuronal
      boutons, underwent strong frequency potentiation and were depressed by activation
      of metabotropic glutamate receptors, which are characteristics of transmission of
      MF origin. Combination of fluorophores can be used to label different
      tracts/boutons allowing the study of the different characteristics of
      neurotransmitter release from a variety of sources on single target cells.

PMID- 22633896
TI  - Antitumor effect of human TRAIL on adenoid cystic carcinoma using magnetic
      nanoparticle-mediated gene expression.
AB  - To overcome treatment limitations of adenoid cystic carcinoma, we developed a
      novel treatment combining gene therapy and nanotechnology. In this study, we
      created a plasmid, pACTERT-TRAIL, which used the human telomerase reverse
      transcriptase promoter, a tumor-specific promoter, to drive tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL). A Fe(3)O(4)-PEI-plasmid complex (FPP)
      was generated, in which the iron oxide nanoparticles were modified by positively
      charged polyethylenimine (PEI) to enable them to carry the negatively charged
      plasmid. In vitro transfection assays showed that efficiency of magnetofection
      (i.e., FPP transfection) was sixfold higher compared to PEI alone or
      Lipofectamine 2000 (hereafter referred to as lipofectin) (P < 0.05). Importantly,
      apoptotic assays demonstrated that FPP-mediated TRAIL gene transfer could
      efficiently induce apoptosis of SACC-83 cells in vitro and in vivo. These results
      demonstrate that magnetofection of the plasmids driven by the tumor-specific
      promoter hTERT provides an effective way to deliver therapeutic genes for the
      treatment of adenoid cystic carcinoma in the future. FROM THE CLINICAL EDITOR: In
      this novel study addressing adenoid cystic carcinoma, the authors created a
      plasmid to drive tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
      Following that, a Fe(3)O(4)-PEI-plasmid complex (FPP) was generated, in which the
      iron oxide nanoparticles were modified by positively charged polyethylenimine
      (PEI) enabling them to carry the negatively charged plasmid, giving rise to
      sixfold higher transfection rates compared to standard technology.

PMID- 22633897
TI  - Polyamidoamine dendrimer nanoparticle cytotoxicity, oxidative stress, caspase
      activation and inflammatory response: experimental observation and numerical
      simulation.
AB  - Mechanisms underlying the in vitro cytotoxicity of Polyamidoamine nano-dendrimers
      in human keratinocytes are explored. Previous studies demonstrated a systematic,
      dendrimer-generation-dependent cytotoxicity, oxidative stress, and genotoxicity.
      The emerging picture is of dendrimer endocytosis, endosomal rupture and
      subsequent mitochondrial attack and cell death. To understand the underlying
      mechanisms, the evolution of reactive oxygen species, intracellular glutathione,
      caspase activation, mitochondrial membrane potential decay, and inflammatory
      responses have been examined. Early-stage responses are associated with endosomal
      encapsulation, later-stage with mitochondrial attack. In all cases, the magnitude
      and evolution of responses depend on dendrimer generation and dose. The early
      stage response is modelled using a rate equation approach, qualitatively
      reproducing the time, dose and generation dependences, using only two variable
      parameters. The dependence of the response on the nanoparticle physicochemical
      properties can thus be separated from internal cellular parameters, and responses
      can be quantified in terms of rate constants rather than commonly employed
      effective concentrations. FROM THE CLINICAL EDITOR: This contribution reports on
      the intracellular mechanism of PAMAM dendrimer cytotoxicity in human
      keratinocytes. In all cases, the magnitude and evolution of responses depend on
      dendrimer generation and dose. Experimental data were supported by numerical
      simulation using only two variables. It is suggested that responses can be
      quantified in terms of rate constants rather than effective concentrations.

PMID- 22633898
TI  - Fibronectin-binding nanoparticles for intracellular targeting addressed by B.
      burgdorferi BBK32 protein fragments.
AB  - Virus-like particles (VLPs) are created by the self-assembly of multiple copies
      of envelope and/or capsid proteins from many viruses, mimicking the conformation
      of a native virus. Such noninfectious nanostructures are mainly used as antigen
      presenting platforms, especially in vaccine research; however, some of them
      recently were used as scaffolds in biotechnology to produce targeted
      nanoparticles for intracellular delivery. This study demonstrates the creation of
      fusion VLPs using hepatitis B core protein-based system maintaining a fibronectin
      binding property from B. burgdorferi BBK32 protein, including the evidence of
      particles' transmission to BHK-21 target cells via caveolae/rafts endocythosis.
      These results make this construct to be an attractive model in development of HBc
      based nanoparticles for cellular targeting applications and highlights the
      fragment of B. burgdorferi BBK32 as a novel cellular uptake-promoting peptide.
      FROM THE CLINICAL EDITOR: This paper discusses the nanotechnology-based
      application of self-assembling viral-like peptides (VLP-s) for targeted delivery
      using a hepatitis B core protein based system. Creating fusion VLPs may be an
      attractive model for cellular targeting applications.

PMID- 22633899
TI  - Poly-lactide-co-glycolide nanoparticles containing voriconazole for pulmonary
      delivery: in vitro and in vivo study.
AB  - Poly-lactide-co-glycolide nanoparticles (207-605 nm) containing voriconazole
      (VNPs) were developed using a multiple-emulsification technique and were also
      made porous during preparation in presence of an effervescent mixture for
      improved pulmonary delivery. Pulmonary deposition of the particles was studied
      using a customized inhalation chamber. VNPs had a maximum of 30% (w/w) drug
      loading and a zeta potential (ZP) value around -20 mV. In the initial 2 hours,
      20% of the drug was released from VNPs, followed by sustained release for 15
      days. Porous particles had a lower mass median aerodynamic diameter (MMAD) than
      nonporous particles. Porous particles produced the highest initial drug
      deposition (~120 MUg/g of tissue). The drug was detectable in lungs until 7 days
      and 5 days after administration, for porous and nonporous particles,
      respectively. VNPs with improved drug loading were successfully delivered to
      murine lungs. Porous nanoparticles with lower MMADs showed better pulmonary
      deposition and sustained presence in lungs. FROM THE CLINICAL EDITOR: In this
      paper, voriconazole-containing porous nanoparticles were studied for inhalational
      delivery to lung infections in a murine model, demonstrating prolonged half-life
      and improved pulmonary deposition.

PMID- 22633900
TI  - Ionizing radiation increases systemic nanoparticle tumor accumulation.
AB  - Nanoparticle-based therapies are currently being explored for both the imaging
      and treatment of primary and metastatic cancers. Effective nanoparticle cancer
      therapy requires significant accumulations of nanoparticles within the tumor
      environment. Various techniques have been used to improve tumor nanoparticle
      uptake and biodistribution. Most notable of these techniques is the use of tumor
      specific peptide-conjugated nanoparticles and chemical modification of the
      nanoparticles with immune-evading polymers. Another strategy for improving the
      tumor uptake of the nanoparticles is modification of the tumor microenvironment
      with a goal of intensifying the enhanced permeability and retention effect
      inherent to solid tumors. We demonstrate a twofold increase in the tumor
      accumulation of systemically delivered iron oxide nanoparticles following a
      single 15-Gy radiation dose in a syngeneic mouse breast tumor model. This
      increase in nanoparticle tumor accumulation correlates with a radiation-induced
      decrease in tumor interstitial pressure and a subsequent increase in vascular
      permeability.

PMID- 22633901
TI  - Enhanced antimicrobial activity of silver nanoparticles synthesized by
      Cryphonectria sp. evaluated singly and in combination with antibiotics.
AB  - The newly identified pathogenic species of the genus Cryphonectria was exploited
      for the synthesis of silver nanoparticles (AgNPs). The extracellular synthesis of
      nanoparticles was fast and eco-friendly. These nanoparticles were analyzed and
      determined by ultraviolet-visible spectrophotometry, which detected AgNPs in the
      solution, and by NanoSight LM20, which determined their average size and
      concentration. The synthesized AgNPs showed a little monodispersity in the range
      of 30-70 nm with a concentration of 6.82 * 10(8) particles per milliliter of
      solution. The AgNPs demonstrated antibacterial activity against Staphylococcus
      aureus, Escherichia coli, Salmonella typhi, and Candida albicans, with
      comparatively higher activity against both S. aureus and E. coli than against S.
      typhi and C. albicans, which showed the lowest activity. The present study
      demonstrates the possible use of biologically synthesized AgNPs in the field of
      medicine. Thus, Cryphonectria sp. could be used for simple, nonhazardous, and
      efficient synthesis of AgNPs. FROM THE CLINICAL EDITOR: In this study
      Cryphonectria sp. was exploited for simple, nonhazardous, and efficient
      biosynthesis of silver nanopartricles, which had antibacterial activity against a
      variety of human pathogenic bacteria.

PMID- 22633902
TI  - The influence of asymmetric quadriceps loading on patellar tracking--an in vitro
      study.
AB  - BACKGROUND: In patients with anterior knee pain and patellar instability, a
      specific training of the quadriceps muscle - especially the vastus medialis - is
      often recommended, although the practicability is discussed controversially and
      the proof of a measurable clinical effect is difficult. Therefore, this in vitro
      study investigates the influence of asymmetric muscle loading on the motion of
      the human patella. METHODS: Seven human knee specimens were tested in a specially
      developed knee simulator. During simulated weight-bearing knee flexion, the
      kinematics of tibia, femur and patella were measured using an ultrasound motion
      capture system. The quadriceps forces were controlled to achieve a constant ankle
      force over the whole flexion range which is assumed to represent almost
      physiological loading. Three different force distributions of the quadriceps were
      tested - a central, equally distributed load as well as mainly lateral and medial
      loads. RESULTS: A significant influence of different quadriceps force
      distributions was found for patellar tilt around a proximodistal axis (up to 1.7
      degrees ) and patellar rotation around an anteroposterior axis (up to 3.8 degrees
      ) with respect to the femur. Interestingly, the patellar mediolateral shift was
      influenced only marginally (<1.5mm). CONCLUSIONS: Specific muscle training might
      help patients with patellofemoral pain and cartilage damage by a slight
      modification of the kinematics, but we could show that even highly asymmetric
      quadriceps loads only led to a small alteration of the mediolateral shift in case
      of a physiologic anatomy of the trochlear groove.

PMID- 22633903
TI  - Compaction properties, drug release kinetics and fronts movement studies of
      matrices combining mixtures of swellable and inert polymers. III: effect of
      polymer substitution type.
AB  - Theophylline radial release from cellulose derivatives with different
      substitution type (HPMC K4M, HPC H, MC A4M) matrix tablets has been modulated by
      the introduction of a new inert polymeric excipient, at different proportions
      (75, 50, 25%). The new polymer was hydroxypropylcellulose-methyl methacrylate
      (HCMMA), which was dried either in a vacuum oven (OD-HCMMA) or freeze-dried (FD
      HCMMA). MC A4M and its mixtures presented the best compaction properties results,
      especially mixed with FD-HCMMA, according to 100% mixtures. Only high levels of
      HCMMA (75%) in the matrices showed interesting differences to drug release
      modulation. Also, at this proportion (75:25), the HPC H mixtures presented the
      highest differences in relation with OD or FD HCMMA respect to the other
      cellulose polymers. HPMC K4M and HPC H mixtures showed a combination of diffusion
      and erosion release mechanisms. The last one was nearly negligible in MC A4M
      mixtures, according with its highest diffusion rate constant values, and the
      absence of hydroxypropyl substituents. Only HPMC K4M mixtures presented a
      diffusion front that moves outwards, while HPC H and MC A4M moves inwards. The
      modulation of theophylline radial release was obtained using a high percentage of
      HCMMA, and the use of two cellulosic ethers, one of them with just one type of
      substituent (MC A4M or HPC H) and the other with two types of substituent (HPMC
      K4M). Another possibility is changing the HCMMA copolymer (OD or FD) in the 75/25
      mixture with HPC.

PMID- 22633905
TI  - Additional, not additive.

PMID- 22633904
TI  - RETRACTED: Influence of choroidal neovascularization and biodegradable polymeric
      particle size on transscleral sustained delivery of triamcinolone acetonide.
AB  - PURPOSE: One objective of this study was to determine whether polymeric
      nanoparticles and/or microparticles sustain transscleral choroidal and retinal
      delivery of triamcinolone acetonide (TA) for two months in therapeutically
      effective concentrations after single periocular administration. Another
      objective of this study was to assess the influence of choroidal
      neovascularization on transscleral delivery of TA. METHODS: Polymeric nano- and
      micro-particles of TA were prepared by o/w emulsion-solvent evaporation method
      using poly-l-lactide (PLA). Particles were characterized for drug loading, size,
      surface morphology, and the in vitro drug release profile. Choroidal
      neovascularization (CNV) was induced in brown Norway (BN) rats using a 532 nm
      diode argon laser and the CNV induction was assessed using fluorescein
      angiography. In vivo delivery was assessed in control and CNV induced rats at 2
      months after periocular injection of TA loaded nano- or micro-particle
      suspension, or plain TA suspension in PBS (pH 7.4). Ocular tissue levels of TA
      were estimated using LC-MS/MS following liquid-liquid extraction of drug from
      tissue samples. Nile red loaded microparticles entrapped in periocular tissue at
      the end of the study was visualized using scanning electron microscopy and
      confocal microscopy. Inhibitory effect of TA on VEGF secretion was evaluated in
      ARPE-19 cells. RESULTS: Triamcinolone acetonide-PLA nano- (551 nm) and micro
      particles (2090 nm), with 14.7 and 29.5% drug loading, respectively, sustained in
      vitro TA release for about 45 and 120 days. After subconjunctival injection,
      microparticles were able to sustain the delivery in all intraocular tissues for 2
      months; whereas no drug levels were detected for TA loaded nanoparticles and
      plain suspension of TA. Intraocular delivery of TA from microparticles was higher
      in CNV induced rats when compared to control rats. Significant amount of
      microparticles remained in periocular tissue at 2 months after injection, and
      maintained spherical shape. TA decreased VEGF secretion by 50% at 0.07 MUM. At
      the end of the in vivo study, choroid-RPE and retina TA levels in CNV induced
      rats were 16- and 5-fold higher than the IC(50) for VEGF secretion. CONCLUSIONS:
      Single periocular injection of polymeric microparticles but not nanoparticles
      sustained effective levels of TA in choroid-RPE and retina for 2 months, with the
      TA delivery being greater in CNV induced rats than the control rats.

PMID- 22633906
TI  - Electroporation of a multivalent DNA vaccine cocktail elicits a protective immune
      response against anthrax and plague.
AB  - Electroporation of DNA vaccines represents a platform technology well positioned
      for the development of multivalent biodefense vaccines. To evaluate this
      hypothesis, three vaccine constructs were produced using codon-optimized genes
      encoding Bacillus anthracis Protective Antigen (PA), and the Yersinia pestis
      genes LcrV and F1, cloned into pVAX1. A/J mice were immunized on a prime-boost
      schedule with these constructs using the electroporation-based TriGrid Delivery
      System. Immunization with the individual pDNA vaccines elicited higher levels of
      antigen-specific IgG than when used in combination. DNA vaccine effectiveness was
      proven, the pVAX-PA titers were toxin neutralizing and fully protective against a
      lethal B. anthracis spore challenge when administered alone or co-formulated with
      the plague pDNA vaccines. LcrV and F1 pVAX vaccines against plague were
      synergistic, resulting in 100% survival, but less protective individually and
      when co-formulated with pVAX-PA. These DNA vaccine responses were Th1/Th2
      balanced with high levels of IFN-gamma and IL-4 in splenocyte recall assays,
      contrary to complimentary protein Alum vaccinations displaying a Th2 bias with
      increased IL-4 and low levels of IFN-gamma. These results demonstrate the
      feasibility of electroporation to deliver and maintain the overall efficacy of an
      anthrax-plague DNA vaccine cocktail whose individual components have qualitative
      immunological differences when combined.

PMID- 22633907
TI  - An apparatus to control and automate the formation of continuous density
      gradients.
AB  - A common problem associated with making a continuous density gradient is the
      unwanted mixing of liquids as the gradient solution is being delivered from the
      gradient mixer to the centrifuge tube. We show that by using a Styrofoam float on
      a thin drawn-out glass pipette, liquids from the gradient mixer will flow down
      the outside surface of the glass fiber and contact the float, after which the
      liquid spreads across the gradient surface without unwanted mixing. As the liquid
      in the tube rises, the float rises up the glass fiber, thereby allowing the
      creation of gradients without the need to monitor the process.

PMID- 22633908
TI  - Asymmetric polymerase chain reaction provides alternatives for preparation of
      (GT)5-tailed duplex DNA promoter for promoter trapping.
AB  - Synthesis of (GT)5-tailed duplex DNA promoter is an important first step for
      purifying transcription complexes by promoter trapping purification. In our
      previous publication, we showed that the purification of the c-jun promoter using
      lambda exonuclease digestion of polymerase chain reaction (PCR) produced DNA with
      single-stranded tails. Asymmetric PCR can also produce tailed single strands that
      can be annealed to yield the desired promoter. An effective method uses
      asymmetric PCR and double digestion. After PCR, first a restriction enzyme, in
      this case SacII, cuts duplex strands remaining after asymmetric PCR, leaving 5'
      phosphoryl ends susceptible to a second digestion with lambda exonuclease to
      effectively degrade any duplex. The resulting single strands are then annealed to
      produce a duplex DNA with a single-stranded (GT)5 tail at the 3' end of each
      strand of the duplex. Unlike the previously described method, this novel
      procedure produces the desired tailed promoter devoid of any untailed duplex.

PMID- 22633909
TI  - Chronic restricted access to food leading to undernutrition affects rat
      neuroendocrine status and olfactory-driven behaviors.
AB  - Previous studies have demonstrated that olfactory-driven behaviors in rats are
      influenced by short-term caloric restriction, partly through the modulation of
      olfactory sensitivity by appetite-modulating hormones or peptides such as insulin
      and leptin. Here, we addressed the issue of a long-term modulation of their
      neuroendocrine status by evaluating the effect of chronic food restriction in
      rats following a limitation of the duration of daily food intake to 2 h (SF)
      instead of 8 h (LF) on the expression of insulin and leptin system in the
      olfactory mucosa and bulb and on olfactory behaviors. This restriction resulted
      in a one-third reduction in the daily food intake and a 25% reduction in the body
      weight of SF rats when compared to controls, and was accompanied by lower levels
      of triglycerides, glucose, insulin and leptin in SF rats. Under these conditions,
      we observed a modulation of olfactory-mediated behaviors regarding food odors. In
      addition, restriction had a differential effect on the expression of insulin
      receptors, but not that of leptin receptors, in the olfactory mucosa, whereas no
      transcriptional change was observed at the upper level of the olfactory bulb.
      Overall, these data demonstrated that long-term changes in nutritional status
      modulate olfactory-mediated behaviors. Modulation of insulin system expression in
      the olfactory mucosa of food restricted rats suggests that this hormone could be
      part of this process.

PMID- 22633910
TI  - Oxytocin antagonist treatments alter the formation of pair relationships in zebra
      finches of both sexes.
AB  - Oxytocin and vasopressin are known to be important in affiliative behaviors.
      Although these peptides have been shown to be involved in monogamous pairing
      behavior in a few mammalian species, their role across monogamous species is not
      well understood. In particular, monogamy is most common in birds, yet the role of
      mesotocin and vasotocin (avian homologues of oxytocin and vasopressin) in pair
      relationships has not been established in any avian species. The goal of the
      present study was to investigate the effects of an oxytocin antagonist on pairing
      and pairing-related behaviors in the monogamous zebra finch. To accomplish this,
      we systemically administered one of three doses of an oxytocin antagonist (1 MUg,
      5 MUg, or 10 MUg) or a vehicle to adult male and female zebra finches (in
      separate experiments) with no prior pairing experience. Subjects were observed
      over three days and allowed to choose mates. We found that oxytocin antagonists
      increased the latency to pair and decreased pair formation in both sexes. The
      effects of these treatments on overall pairing behaviors were more pronounced in
      females than in males, suggesting sexually differentiated effects on motivation
      to contact conspecifics. Treatments also reduced courtship, as measured by
      directed singing, in males. These results suggest that nonapeptides play a key
      role in pair formation in zebra finches of both sexes, similar to findings in
      other monogamous species.

PMID- 22633911
TI  - Superoxide dictates the mode of U937 cell ascorbic acid uptake and prevents the
      enhancing effects of the vitamin to otherwise nontoxic levels of reactive
      oxygen/nitrogen species.
AB  - Exposure of U937 cells to low micromolar levels of ascorbic acid or
      dehydroascorbic acid, while resulting in identical ascorbic acid accumulation, is
      unexpectedly associated with remarkably different responses to exogenous
      oxidants. We observed that otherwise nontoxic levels of hydrogen peroxide, tert
      butylhydroperoxide or peroxynitrite promote toxicity in cells preloaded with
      ascorbic acid, whereas hardly any effect was detected in cells pretreated with
      dehydroascorbic acid. Further experiments performed with peroxynitrite in cells
      preloaded with ascorbic acid provided evidence for a very rapid nonapoptotic
      death, preceded by early Bax mitochondrial translocation and by mitochondrial
      permeability transition. The notion that conversion of extracellular ascorbic
      acid to dehydroascorbic acid prevents the enhancing effects on oxidant toxicity
      and nevertheless preserves the net amount of vitamin C accumulated was also
      established using ascorbate oxidase as well as various sources of superoxide,
      namely, xanthine/xanthine oxidase or ATP-driven NADPH oxidase activation. These
      findings suggest that superoxide-dependent conversion of extracellular ascorbic
      acid to dehydroascorbic acid represents an important component of the overall
      survival strategy of some cell types to reactive oxygen/nitrogen species.

PMID- 22633912
TI  - Phase-separation of mixed surfactant monolayers: a comparison of film morphology
      at the solid-air and liquid-air interfaces.
AB  - The morphologies of phase-separated monolayer films prepared from two different
      binary mixtures of perfluorocarbons and hydrocarbons have been examined and
      compared, for the first time, at the solid-air and liquid-air interfaces. Films
      were comprised of binary mixtures of arachidic acid (C(19)H(39)COOH) with
      perfluorotetradecanoic acid (C(13)F(27)COOH) and of palmitic acid
      (C(15)H(31)COOH) with perfluorooctadecanoic acid (C(17)F(35)COOH). For both mixed
      systems, Langmuir Blodgett films on mica substrates consisted of polygonal
      domains of one surfactant dispersed in a continuous matrix of the other
      (arachidic acid in perfluorotetradecanoic acid or perfluorooctadecanoic acid in
      palmitic acid, respectively), consistent with previous reports. Real-time imaging
      of the air-water interface via Brewster angle microscopy revealed that comparable
      film morphology was present at the air-water interface and the solid-air
      interface over a wide range of surface pressures, and that for the arachidic acid
      based mixture, domain growth dynamics at the air-water interface is consistent
      with that inferred from sequential "static" atomic force microscope images
      collected at the solid-air interface.

PMID- 22633913
TI  - Participating in a policy debate program and academic achievement among at-risk
      adolescents in an urban public school district: 1997-2007.
AB  - This study investigates the relationship between participating in a high school
      debate program on college-readiness in the Chicago Public School district over a
      10-year period. At-risk school students were identified using an index including
      8th grade achievement, poverty status, and enrollment in special education.
      Regression analyses were used to assess the association between debate
      participation and graduation and ACT performance. Overall, debaters were 3.1
      times more likely to graduate from high school (95% confidence interval: 2.7-3.5)
      than non-debaters, and more likely to reach the college-readiness benchmarks on
      the English, Reading, and Science portions of the ACT. This association was
      similar for both low-risk and at-risk students. Debate intensity was positively
      related to higher scores on all sections of the ACT. Findings indicate that
      debate participation is associated with improved academic performance for at-risk
      adolescents.

PMID- 22633914
TI  - Individualism and socioeconomic diversity at school as related to perceptions of
      the frequency of peer aggression in fifteen countries.
AB  - The purpose of this study was to examine two aspects of context for peer
      aggression: national individualism and distributions of socioeconomic status in
      the school. School administrators for each school reported on their perceptions
      of the frequency of bullying and violence in their school. The sample comprised
      990 school principals/headmasters from nationally representative samples of
      schools in 15 countries surveyed as part of the larger IEA Civic Education Study
      (Torney-Purta, Lehmann, Oswald, & Schulz, 2001). A national context of
      individualism was associated with violence but not bullying. Schools with high
      socioeconomic diversity had more bullying than homogeneously low or high
      socioeconomic status schools. In addition, diverse schools had more violence than
      affluent schools. Results suggest that bullying and violence should be
      investigated as separate constructs. Furthermore, contexts, such as national
      culture and school socioeconomic diversity, are important in understanding the
      prevalence of bullying and violence in schools internationally.

PMID- 22633915
TI  - A two-method investigation of early adolescents' responses upon witnessing peer
      victimization in school.
AB  - Given the passivity of many adolescents upon witnessing peer victimization, the
      goal of this study was to evaluate the features of school-based peer
      victimization events that promote helping. A sample of 470 early adolescents (52%
      girls; 71% White, 9% Black, 6% Latino, 2% Asian, 1% American Indian, 8%
      Multiethnic, and 3% Other) reported likelihood of helping and specific helping
      and non-helping behaviors with an experimental vignette method and through
      descriptions of recently witnessed real-life victimization events. With both
      methods, an adolescent's relationship with the victim predicted likelihood of
      helping and specific helping behaviors above and beyond the contribution of other
      key personal characteristics including gender, empathy, communal goal
      orientation, and previous victimization experiences. Examination of adolescents'
      real-life experiences yielded systematic patterns between their responses and
      their reasoning about the responses undertaken. The results illustrate the
      relevance of taking into account peer victimization event characteristics for
      promoting witness intervention in adolescence.

PMID- 22633917
TI  - A comparison of two different continuous theta burst stimulation paradigms
      applied to the human primary motor cortex.
AB  - OBJECTIVE: The application of repetitive transcranial magnetic stimulation (rTMS)
      in bursts at theta frequencies (TBS) may produce lasting neuroplastic changes in
      the human cortex. However, there exists high variability in subjects' responses,
      possibly due to non-optimal stimulation characteristics. Here we compare the
      efficacy of two variations of continuous TBS (cTBS) for producing neuroplastic
      change in the human primary motor cortex (M1). METHODS: The two cTBS paradigms
      were: (1) standard cTBS (cTBS(std)) (three stimuli at 50Hz, repeated at 5Hz), and
      (2) modified cTBS (cTBS(mod)) (three stimuli at 30Hz, repeated at 6Hz with
      intensity). Motor evoked potentials (MEPs) were recorded from the right first
      dorsal interosseous muscle before, as well as at 0, 5, 10, 20 and 30min following
      each paradigm. RESULTS: Both cTBS(std) (P=0.05) and cTBS(mod) (P<0.0001) induced
      a suppression of MEP amplitudes. However, MEP suppression following cTBS(mod) was
      greater (ANOVA(RM); P=0.02). Experiments using magnetic brainstem stimulation
      provided evidence that cTBS(mod) induced MEP suppression through cortical
      mechanisms. CONCLUSIONS: The neuroplastic response of the human M1 to cTBS is
      highly dependent on the stimulation parameters employed. SIGNIFICANCE: These
      findings may have significant implications for the clinical application of cTBS
      paradigms.

PMID- 22633916
TI  - Acute effects of thalamic deep brain stimulation and thalamotomy on sensorimotor
      cortex local field potentials in essential tremor.
AB  - OBJECTIVE: Essential tremor (ET) is characterized by an action tremor believed to
      be due to excessive theta-alpha activity in the cerebello-thalamo-cortical
      system. This study aimed to test the hypothesis that therapeutic thalamic
      stimulation in patients with ET decreases theta-alpha oscillatory activity in
      primary motor (M1) and sensory (S1) cortices. METHODS: During surgical treatment
      of ET in 10 patients, an electrocorticography (ECoG) strip electrode was placed
      temporarily over the arm region of M1 and S1. Local field potentials (LFP) were
      recorded at rest, during a tremor-inducing posture, during acute therapeutic
      thalamic stimulation, and following therapeutic thalamotomy (three patients).
      Power spectral density (PSD) was calculated using the Fast Fourier Transform.
      RESULTS: At rest, alpha activity (8-13Hz) in M1 was significantly decreased
      during high-frequency stimulation, while theta activity (4-8Hz) decreased in S1.
      Following thalamotomy, theta and beta (13-30Hz) was increased in M1. Induction of
      postural tremor reduced M1 theta, alpha and beta activity compared to the resting
      state. CONCLUSIONS: High-frequency thalamic deep brain stimulation (DBS)
      significantly reduces alpha oscillatory activity in the primary motor cortex of
      patients with ET, though this change is probably not critical for therapeutic
      efficacy. SIGNIFICANCE: We demonstrate that ECoG can be effectively used to study
      the effect of subcortical stimulation on cortical oscillations.

PMID- 22633918
TI  - Validation of head movement correction and spatiotemporal signal space separation
      in magnetoencephalography.
AB  - OBJECTIVE: Our aim was to assess the effectiveness and reliability of
      spatiotemporal signal space separation (tSSS) and movement correction (MC) in
      magnetoencephalography (MEG) recordings disturbed by head movements and
      magnetized material on the head. METHODS: We recorded MEG from 20 healthy adults
      in stationary (reference) head position and during controlled head movements.
      Nearby magnetic interference sources were simulated by attaching magnetized
      particles on the subject's head. Auditory and somatosensory stimuli were
      presented. MC, tSSS and averaging were performed to obtain auditory (AEF) and
      somatosensory (SEF) evoked fields. Neuronal sources were modeled as equivalent
      current dipoles. MC was also validated by reconstructing signals generated by
      current dipoles in a phantom. RESULTS: After MC, the AEF and SEF responses
      recorded during intermittent head movements were similar in amplitude to the
      reference recordings and differed by 5-7mm in source location. The tSSS method
      removed artifacts due to the attached magnetized particles but did not affect the
      reference data. CONCLUSIONS: The methods are able to reliably recover MEG
      responses contaminated by movements and magnetic artifacts on the head.
      SIGNIFICANCE: The combination of tSSS and MC methods is especially useful in
      clinical measurements, where movements and magnetic disturbances are commonly
      present.

PMID- 22633919
TI  - Deactivation of the parvalbumin-positive interneurons in the hippocampus after
      fear-like behaviour following electrical stimulation of the dorsolateral
      periaqueductal gray of rats.
AB  - The majority of patients with panic disorder express a fearful sensation when
      encountered with panic-related cues. A subpopulation of GABAergic interneurons in
      the hippocampus has been demonstrated in the regulation of behavioural learning,
      especially during the contextual fear-conditioning. Here, we examined the
      influence of panic/fear response induced by deep brain stimulation (DBS) of the
      periaqueductal gray on these hippocampal parvalbumin-positive interneurons. We
      found that fear-like behaviour did not change the number of c-Fos immunoreactive
      and parvalbumin-positive cells. However, a remarkable decrease of c-Fos and
      parvalbumin co-localization was shown in the hippocampal regions when compared to
      non-stimulated sham animals. In line with previous studies, our results support
      the hypothesis that GABAergic regulation resulted in enhanced behavioural
      reactivity to fear conditioning. In conclusion, our findings indicate that the
      inhibition of this subpopulation of hippocampal parvalbumin-positive interneurons
      induced a long lasting anxiety- or fear-like behaviour.

PMID- 22633920
TI  - Maternal high-fat diet in mice programs emotional behavior in adulthood.
AB  - The maternal environment has a significant role in the normal development of the
      fetus and may have long-term impact on brain development including critical
      central pathways such as the gamma-aminobutyric acid (GABA), serotonergic and the
      neurotrophin systems. For example, maternal malnutrition plays an important role
      in programming many aspects of physiology and behavior including predisposition
      to mental-health related disorders such as anxiety. Here we investigated the
      effects of maternal high-fat diet or control diet for nine weeks (prior to
      gestation, gestation and lactation) on the adult offspring with respect to
      anxiety related behaviors as well as exploration and conditioned fear response.
      We found that offspring born to high-fat diet mothers showed increased anxiety
      like behaviors, but intact conditioned fear response and exploratory behavior. In
      addition, brain-derived neurotrophic factor (BDNF) was significantly increased in
      the dorsal hippocampus, while GABA(A) alpha2 receptor subunit and 5
      hydroxytryptamine 1A (5-HT1A) receptor showed increased levels in the ventral
      hippocampus. In summary, these findings suggest that maternal high-fat diet
      consumption during critical periods in the development of the fetus, might
      increase the risk of abnormal behaviors in adulthood related to anxiety.

PMID- 22633921
TI  - Systematic autistic-like behavioral phenotyping of 4 mouse strains using a novel
      wheel-running assay.
AB  - Three core symptoms of autistic spectrum disorders are stereotypic movements,
      resistance to change in routines and deficits in social interaction. In order to
      understand their neuronal mechanisms, there is a dire need for behavioral
      paradigms to assess those symptoms in rodents. Here we present a novel method
      which is based on positive reward in a customized wheel-running apparatus to
      assess these symptoms. As a proof of concept, 4 mouse strains were tested in the
      new behavioral paradigm; 2 control lines (C57BL/6 and ICR) and 2 mouse-models of
      autism (BTBR T+ tf/J and Nlgn3(tm1Sud)). We found that the C57BL/6, ICR and
      Nlgn3(tm1Sud) mice showed a significant reduction in stereotypical behavior in
      the presence of the running wheel, ability to forfeit the running habit when the
      running-wheel was jammed, and preference of interacting with a social stimulus
      over the jammed running-wheel. No difference was found between genotypes of the
      Nlgn3(tm1Sud) mice. On the other hand, the BTBR mice exhibited persistent,
      elevated levels of stereotypical behavior. In addition, they presented a deficit
      in their ability to adjust to a changing environment, as manifested in
      persistence to interact with the wheel even when it was jammed. Lastly, the BTBR
      mice exhibited no significant preference to interact with the stranger mouse over
      the jammed running-wheel. These results were validated by a set of commonly used
      behavioral tests. Overall, our novel behavioral paradigm detects multiple
      components of autistic-like phenotypes, including cognitive rigidity, stereotypic
      behavior and social deficiency.

PMID- 22633922
TI  - The Great White Train: typhus, sanitation, and U.S. International Development
      during the Russian Civil War.

PMID- 22633923
TI  - Tertiary treatment of pulp mill wastewater by solar photo-Fenton.
AB  - This work reports on pulp mill wastewater (PMW) tertiary treatment by Fenton
      (Fe(2+)/H(2)O(2)) and solar photo-Fenton (Fe(2+)/H(2)O(2)/UV) processes in a
      pilot plant based on compound parabolic collectors (CPCs). Solar photo-Fenton
      reaction is much more efficient than the respective dark reaction under identical
      experimental conditions. It leads to DOC mineralisation, COD and total
      polyphenols (TP) removal higher than 90%. The solar photo-Fenton experiment with
      5mg Fe L(-1) reaches 90% of DOC mineralisation with 31kJ L(-1) of UV energy and
      50mM of H(2)O(2). The initial non-biodegradability of PMW, as shown by
      respirometry assays and BOD(5)/COD ratio, can be changed after a solar photo
      Fenton treatment. Experiments with 20 and 50mg Fe L(-1) revealed that solar photo
      Fenton can reach the same DOC degradation (90%), however, consuming less H(2)O(2)
      and time. Diluting the initial organic load to 50% also diminishes the dosage of
      H(2)O(2) and the necessary reaction time to achieve high DOC removals.
      Accordingly, solar photo-Fenton can be considered an alternative or complementary
      process to improve the performance of a biologic treatment and, subsequently,
      achieve legal limits on discharge into natural waters.

PMID- 22633924
TI  - Effect of surface coating and organic matter on the uptake of CeO2 NPs by corn
      plants grown in soil: Insight into the uptake mechanism.
AB  - Little is known about the fate, transport, and bioavailability of CeO(2)
      nanoparticles (NPs) in soil. Moreover, there are no reports on the effect of
      surface coating upon NPs uptake by plants. In this study, Zea mays plants were
      grown for one month in unenriched and organic soils treated with coated and
      uncoated CeO(2) NPs. In addition, plants were exposed to fluorescein
      isothiocyanate (FITC)-stained CeO(2) NPs and analyzed in a confocal microscope.
      In organic soil, roots from uncoated and coated NPs at 100, 200, 400, and 800mg
      kg(-1) had 40, 80, 130, and 260% and 10, 70, 90, and 40% more Ce, respectively,
      compared to roots from unenriched soil. Conversely, shoots of plants from
      unenriched soil had significantly more Ce compared with shoots from organic soil.
      Confocal fluorescence images showed FITC-stained CeO(2) NP aggregates in cell
      walls of epidermis and cortex, suggesting apoplastic pathway. The MUXRF results
      revealed the presence of CeO(2) NP aggregates within vascular tissues. To the
      authors knowledge this is the first report on the effects of surface coating and
      organic matter on Ce uptake from CeO(2) NPs and upon the mechanisms of CeO(2) NPs
      uptake by higher plants.

PMID- 22633925
TI  - Activities of nitrate reductase and glutamine synthetase in rice seedlings during
      cyanide metabolism.
AB  - A study was conducted to investigate activities of nitrate reductase (NR) and
      glutamine synthetase (GS) in plants during cyanide metabolism. Young rice
      seedlings (Oryza sativa L. cv. XZX 45) were grown in the nutrient solutions
      containing KNO(3) or NH(4)Cl and treated with free cyanide (KCN). Cyanide in
      solutions and in plant materials was analyzed to estimate the phyto-assimilation
      potential. Activities of NR and GS in different parts of rice seedlings were
      assayed in vivo. Seedlings grown on NH(4)(+) showed significantly higher relative
      growth rate than those on NO(3)(-) (p<0.05) in the presence of exogenous cyanide.
      The metabolic rates of cyanide by seedlings were all positively correlated to the
      concentrations supplied. A negligible difference was observed between the two
      treatments with nitrate and ammonium (p>0.05). Enzymatic assays showed that
      cyanide (>=0.97mg CN L(-1)) impaired NR activity significantly in both roots and
      shoots (p<0.05). The effect of cyanide on GS activity in roots was more evident
      at 1.93mg CN L(-1), suggesting that NR activity was more susceptible to change
      from cyanide application than GS activity. The results observed here suggest that
      the exogenous cyanide, which to a certain level has a beneficial role in plant
      nutrition.

PMID- 22633926
TI  - Establishment of a duck cell line susceptible to duck hepatitis virus type 1.
AB  - Until recently, there was no cell line that could produce continuously high-titer
      duck hepatitis virus type 1 (DHV-1). In this study, a duck embryo fibroblast
      (DEF) cell line was established, and the susceptibility of this cell line to DHV
      1 was determined. The primary culture of DEF cells was from a duck embryo that
      was partially digested with trypsin. Digested tissue pieces were cultured at 37
      degrees C in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine
      serum. The cultured DEF cells, which had the morphology of fibroblast,
      proliferated to 100% confluence four days later. An immortalized DEF cell line,
      named DEF-TA, was established and subcultured to passage 33, and the
      susceptibility of that cell line to DHV-1 was determined. In the DHV-1
      susceptibility tests, cytopathic effects and the propagation of virus were
      observed in DEF-TA cells after DHV-1 infection. This continuous DHV-1-susceptible
      DEF cell line may serve as a valuable cell line for studies of cell-virus
      interactions and the pathogenesis of DHV-1 and may be useful for the development
      of an inactivated vaccine.

PMID- 22633927
TI  - Nested PCR detection of abalone shriveling syndrome-associated virus in China.
AB  - Haliotis diversicolor (small abalone) is an economic seafood found off the
      Southern coast of China. Since 1999, the cultured abalone yields in China have
      been affected severely by continual outbreaks of a fatal epidemic disease caused
      by abalone shriveling syndrome associated virus (AbSV), a double-stranded DNA
      virus. Although the pathogenicity and genome of AbSV have been ascertained, the
      epidemiology of AbSV infection remains to be investigated. In the present study,
      four pairs of AbSV-specific primers were designed on the basis of open reading
      frame (ORF)24 and ORF25 sequences in the AbSV genome. Two nested PCR detection
      methods were established by optimization of the annealing temperatures of
      primers. The results showed that the specificity of primers for AbSV detection
      could not be interfered with by the host genome and other aquaculture species or
      viruses. The detection limits of the two methods were about 10 copies of
      recombinant plasmid containing AbSV genes in 20MUL reaction mixture. The results
      of detection of the AbSV epidemic showed that AbSV was still present in juvenile
      abalones in some farms along the Southern coast of China (Fujian and Guangdong).

PMID- 22633928
TI  - Pre-analytical and analytical procedures for the detection of enteric viruses and
      enterovirus in water samples.
AB  - Practical pre-analytical and analytical procedures were developed and validated
      for detection of enteric viruses in three water matrices. Both RNA viruses
      (norovirus, coxsackievirus, echovirus, and rotavirus) and DNA virus (adenovirus
      41) were included in the study. The NanoCeram 90mm laminated disc with
      electropositive filter and procedures of filtration, elution and flocculation
      were utilized to concentrate known amount of viruses in different water matrices.
      Real time quantitative PCR was used to evaluate the recovery of virus and cell
      culture to assess viral infectivity. There was no PCR inhibition using various
      concentrations and pH of beef extract eluting buffer. A good recovery of the
      viruses spiked in 10L of deionized water was achieved for serial dilutions of
      coxsackievirus (41-67%), echovirus (22-90%), norovirus (23-44%) and rotavirus (24
      46%). Relatively lower recovery was observed for adenovirus 41 (24-35%). There
      was no significant difference in viral recovery from deionized, tap and river
      water samples. The infectivity of recovered adenovirus, coxsackievirus and
      echovirus was demonstrated using in vitro cell culture. The pre-analytical and
      analytic procedures attained consistent recovery of RNA and DNA viruses both as
      infectious viral particles and viral genome, provided effective removal of
      inhibitory substances, achieved reliable reproducibility, and were relatively
      inexpensive for monitoring viruses in water.

PMID- 22633929
TI  - Modulated iontophoretic delivery of small and large molecules through
      microchannels.
AB  - The objective of this work was to modulate transdermal drug delivery by
      iontophoresis though skin microchannels created by microneedles. Calcein and
      human growth hormone were used as a model small and large molecule, respectively.
      In vitro permeation studies were performed on porcine ear skin under three
      different settings: (a) modulated iontophoresis alone, (b) pretreatment with
      microneedles and (c) combination of microneedles pretreatment and modulated
      iontophoresis. For modulated iontophoresis, 0.5 mA/cm(2) current was applied for
      1h each at 2nd and 6th hour of the study. Methylene blue staining, calcein
      imaging and pore permeability index suggested maltose microneedles created
      uniform microchannels in skin. Application of iontophoresis provided two peaks in
      flux of 1.04 MUg/(cm(2)h) at 4th hour and 2.09 MUg/(cm(2)h) at 8th hour of study
      for calcein. These peaks in flux were significant higher when skin was pretreated
      with microneedles (p<0.05). Similarly, for human growth hormone, modulation in
      transdermal flux was achieved with combination of microneedles and iontophoresis.
      This combination also provided significant increase in cumulative amount of
      calcein and human growth hormone delivered as compared to microneedles or
      iontophoresis alone (p<0.05). Therefore, iontophoresis can be used to modulate
      drug delivery across skin microchannels created by microneedles.

PMID- 22633930
TI  - Design and characterization of submicron formulation for a poorly soluble drug:
      the effect of Vitamin E TPGS and other solubilizers on skin permeability
      enhancement.
AB  - In transdermal drug delivery systems (TDDS), it is a challenge to achieve stable
      and prolonged high permeation rates across the skin since the concentrations of
      the drug dissolved in the matrix have to be high in order to maintain zero order
      release kinetics. Several attempts have been reported to improve the permeability
      of poorly soluble drug compounds using supersaturated systems, however, due to
      thermodynamic challenges, there was a high tendency for the drug to nucleate
      immediately after formulating or even during storage. The present study focuses
      on the efficiency of drug crystals at the submicron/nano range in presence of
      different solubilizers to improve the permeation rate. Effect of several
      solubilizers, e.g. Pluronic F-127, Vitamin E TPGS, propylene glycol were studied
      on the submicron suspension systems of ibuprofen as a model drug. Various
      stabilizers such as hydroxylpropyl methylcellulose (HPMC) and
      polyvinylpyrrolidone (PVP) were examined to evaluate their crystal inhibitory
      effects on particle growth of the drug compound at submicron range. The overall
      permeation enhancement process through the skin seems to be influenced by the
      presence of solubilizers and also the presence of submicron drug crystal. The
      most promising stable formulation was developed with Vitamin E TPGS+HPMC
      submicron suspension, which produced higher permeation rate compared to other
      vehicles.

PMID- 22633932
TI  - What is the key environmental trigger in type 1 diabetes--is it viruses, or wheat
      gluten, or both?
AB  - Prevention and treatment of type 1 diabetes is hampered by the fact that the key
      environmental trigger(s) of the disease is still unknown. Much of the data on
      this subject points to two possibilities, viruses and wheat gluten. Viruses
      appear to be involved as an etiological agent in some cases of type 1 diabetes,
      particularly in fulminant type 1 diabetes. Further analysis of the data suggests
      that viruses are not the sole trigger of type 1 diabetes in humans, and that
      wheat gluten may play a role in initiating the disease. Viruses may be the key
      environmental trigger in some cases of type 1 diabetes, and wheat gluten in
      others. Conceivably, some cases of type 1 diabetes might be caused by viruses and
      wheat gluten acting together as disease triggers.

PMID- 22633933
TI  - Invited commentary.

PMID- 22633931
TI  - Co-administration strategy to enhance brain accumulation of vandetanib by
      modulating P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein
      (Bcrp1/Abcg2) mediated efflux with m-TOR inhibitors.
AB  - The objectives of this study were (i) to characterize the interaction of
      vandetanib with P-glycoprotein (P-gp) and breast cancer resistance protein
      (Bcrp1) in vitro and in vivo (ii) to study the modulation of P-gp and BCRP
      mediated efflux of vandetanib with specific transport inhibitors and m-TOR
      inhibitors, everolimus and temsirolimus. Cellular accumulation and bi-directional
      transport studies in MDCKII cell monolayers were conducted to delineate the role
      of efflux transporters on disposition of vandetanib. Brain distribution studies
      were conducted in male FVB wild-type mice with vandetanib administered
      intravenously either alone or in the presence of specific inhibitors and m-TOR
      inhibitors. In vitro studies suggested that vandetanib is a high affinity
      substrate of Bcrp1 but is not transported by P-gp. Interestingly, in vivo brain
      distribution studies in FVB wild type mice indicated that vandetanib penetration
      into the brain is restricted by both Bcrp1 and P-gp mediated active efflux at the
      blood brain barrier (BBB). Co-administration of elacridar, a dual P-gp/BCRP
      inhibitor increased the brain to plasma concentration ratio of vandetanib upto 5
      fold. Of the two m-TOR pathway inhibitors examined; everolimus showed potent
      effect on modulating vandetanib brain penetration whereas no significant affect
      on vandetanib brain uptake was observed following temsirolimus co-administration.
      This finding could be clinically relevant as everolimus can provide synergistic
      pharmacological effect in addition to primary role of vandetanib efflux
      modulation at BBB for the treatment of brain tumors.

PMID- 22633934
TI  - Contribution of BK(Ca) channels of neurons in rostral ventrolateral medulla to CO
      mediated central regulation of respiratory rhythm in medullary slices of neonatal
      rats.
AB  - We recently described that carbon monoxide (CO) participated in the regulation of
      rhythmic respiration in medullary slices. The present study was undertaken to
      further assess whether the large-conductance calcium-activated potassium channels
      (BK(Ca) channels) are involved in the CO-mediated central regulation of
      respiratory rhythm in medullary slices. The rhythmic discharge of hypoglossal
      rootlets of medullary slices of neonatal rats was recorded. We observed that
      blocking BK(Ca) channels could partially abolish the effects of CO on the
      rhythmic bursts of hypoglossal rootlets. With whole-cell patch-clamp recording
      technique, we further observed that CO could reversibly augment potassium current
      density of the neurons in the rostral ventrolateral medulla. The CO-induced
      increase in potassium current was entirely blocked by the pretreatment of slices
      with BK(Ca) channels blocker; whereas blockade of CO generation with zinc
      protoporphyrin-IX produced an opposite response. Altogether, these data indicate
      that BK(Ca) channels of the neurons in neonatal rostral ventrolateral medulla
      could be activated by CO and involved in CO-mediated central regulation of
      respiratory rhythm in medullary slices.

PMID- 22633935
TI  - Do segmental reflexes play a role in the distribution of external intercostal EMG
      activity in the rabbit?
AB  - External intercostal muscle is considered as an inspiratory muscle. Its
      electromyographic (EMG) activity is exquisitely sensitive to proprioceptive
      afferents and is predominant in zones with the greatest respiratory effect. In
      the current series of studies, we assessed the contribution of segmental reflexes
      to this particular distribution of activity in anesthetized rabbits. We first
      established a parallel between gradients of activity and mechanical advantage.
      The sensitivity of external intercostal EMG activity to rib displacement was then
      assessed in the 3rd and 5th interspaces and in the dorsal, middle and ventral
      muscle bundles of the 3rd interspace. Finally, persistence of the dorso-ventral
      gradient was tested after a dorsal rhizotomy (interspaces 3-5). There were no
      differences in the sensitivity to rib motion in the studied positions. After
      rhizotomy, the dorso-ventral gradient of activity persisted at rest and with
      inspiratory resistive loading. We, therefore, conclude that the neuromechanical
      matching of respiratory drive in the external intercostal muscles is not the
      result of segmental reflexes.

PMID- 22633936
TI  - Glucocorticoid decreases airway tone via a nongenomic pathway.
AB  - Nocturnal asthma is associated with circadian rhythms. Although glucocorticoids
      have contributed to therapeutic success, the underlying mechanism has not been
      studied thoroughly in asthma. Here, we report that cortisol, a member of
      glucocorticoids, ameliorate guinea pig tracheal spasm via a nongenomic effect. We
      set a concentration gradient of cortisol to mimic the functional circadian
      fluctuation. When administrated over a threshold (150 ng/ml), cortisol could
      synergize with the spasmolytic action of beta-agonist (isoprenaline) in histamine
      sensitized tracheal spirals in vitro. This permissive action was abolished by the
      glucocorticoid receptor antagonist, RU486, indicating that cortisol acts via its
      receptor. Using the RNA polymerase inhibitor, actinomycin D, we showed that this
      permissive action was not affected by transcription. PMA, activator of protein
      kinase C (PKC), could partially imitate this rapid effect, while PKC inhibition
      also blocked this action to some extent. It is likely that this nongenomic effect
      of glucocorticoid underlies the onset and susceptibility of asthma, implying
      novel medication target in clinical practice.

PMID- 22633937
TI  - Effects of aerobic exercise on chronic allergic airway inflammation and
      remodeling in guinea pigs.
AB  - We evaluated the effects of aerobic exercise (AE) on airway inflammation, exhaled
      nitric oxide levels (ENO), airway remodeling, and the expression of Th1, Th2 and
      regulatory cytokines in a guinea pig asthma model. Animals were divided into 4
      groups: non-trained and non-sensitized (C), non-sensitized and AE (AE), ovalbumin
      sensitized and non-trained (OVA), and OVA-sensitized and AE (OVA+AE). OVA
      inhalation was performed for 8 weeks, and AE was conducted for 6 weeks beginning
      in the 3rd week of OVA sensitization. Compared to the other groups, the OVA+AE
      group had a reduced density of eosinophils and lymphocytes, reduced expression of
      interleukin (IL)-4 and IL-13 and an increase in epithelium thickness (p<0.05). AE
      did not modify airway remodeling or ENO in the sensitized groups (p>0.05).
      Neither OVA nor AE resulted in differences in the expression of IL-2, IFN-gamma,
      IL-10 or IL1-ra. Our results show that AE reduces the expression of Th2 cytokines
      and allergic airway inflammation and induces epithelium remodeling in sensitized
      guinea pigs.

PMID- 22633938
TI  - A comparison of single breath and re-breathe diffusing capacity in emphysema
      patients and controls.
AB  - In emphysema patients, gas dilutional alveolar volume is underestimated by a 10s
      single breath maneuver at total lung capacity (TLC) compared with re-breathing at
      functional residual capacity (FRC); corresponding underestimation of single
      breath diffusing capacity (DLCO) in emphysema has not been demonstrated. The
      purpose of this study was to quantify the degree to which re-breathe DLCO at FRC
      (DLCO(RB)) differs from single breath DLCO at TLC (DLCO(SB)) in emphysema. In 37
      consecutively recruited patients with moderate to severe emphysema (FEV1/FVC
      40%+/-10% predicted), DLCO(RB) as % predicted of 91 controls without
      cardiopulmonary disease was 79%+/-24%, significantly greater than % predicted
      DLCO(SB) (44%+/-19%; p<0.0001). DLCO(RB)/DLCO(SB) was inversely proportional to
      FEV1% predicted (R = -0.47, p=0.004), and FEV1/FVC (R = -0.54, p<0.001). These
      data indicate that a 10s single breath DLCO maneuver progressively under
      represents re-breathe lung diffusing capacity in emphysema as airflow obstruction
      increases.

PMID- 22633939
TI  - Survival among non-small cell lung cancer patients with poor performance status
      after first line chemotherapy.
AB  - BACKGROUND: Performance status (PS) is a commonly used factor in determining the
      appropriateness for chemotherapy of patients with non-small cell lung cancer
      (NSCLC). The prevalence of poor PS and impact of chemotherapy on survival among
      NSCLC patients has not been studied in community populations. PATIENTS AND
      METHODS: Insured patients, aged 50+ years, diagnosed with advanced stage NSCLC
      between 2000 and 2007 were identified via tumor registry (n=292) and linked to
      electronic medical records, automated medical claims, and Census tract
      information. A multivariate Cox proportional hazards model was used to determine
      the factors associated with survival. RESULTS: Of 292 stage IIIB-IV patients, 82
      (28%) had PS 3 or 4, and 39% of PS 3-4 patients received first line chemotherapy.
      Those who received chemotherapy lived 4.8 months compared to 2.4 months for those
      who did not. Factors associated with a reduced likelihood of death included
      receipt of chemotherapy (hazard ratio [HR], 0.64), and female gender (HR, 0.71).
      Modern chemotherapy may be associated with positive effects on survival for poor
      PS patients, as for good PS patients. Further trials, especially randomized
      trials, in this neglected subgroup are indicated.

PMID- 22633940
TI  - Electrogenerated chemiluminescence biosensing method for the detection of DNA
      methylation and assay of the methyltransferase activity.
AB  - A novel electrogenerated chemiluminescence (ECL) biosensing method for highly
      sensitive detection of DNA methylation and assay of the CpG methyltransferase (M.
      SssI) activity was developed on basis of enzyme-linkage reactions and ruthenium
      complex served as an ECL tag. The ECL biosensing electrode was fabricated by self
      assembling 5'-thiol modified 32-mer single-strand DNA (ss-DNA)-tagged with
      ruthenium bis (2,2'-bipyridine) (2,2'-bipyridine-4,4'-dicarboxylic acid)
      ethylenediamine on the surface of a gold electrode, and then hybridized with
      complementary ss-DNA to form duplex DNA (ds-DNA). When M. SssI and S
      adenosylmethionine were introduced, all cytosine residues within 5'-CG-3' of ds
      DNA on the biosensing electrode were methylated. After the methylated biosensing
      electrode was treated by HpaII endonuclease, the un-methylated cytosines were
      cleaved, thus led to decrease ECL signal. The ECL intensity of ECL biosensing
      electrode is related to the methylation level and M. SssI activity in a fixed
      concentration HpaII endonuclease. The increased ECL intensity was direct
      proportion to M. SssI activity in the range from 0.05 to 100 U/mL with a
      detection limit of 0.02 U/mL. This work demonstrates that the combination of the
      enzyme-linkage reactions with a highly sensitive ECL technique is a great
      promising approach for the detection of DNA methylation level, assay of the
      activity of MTase, and evaluation of the capability of inhibitors for the
      methyltransferase.

PMID- 22633941
TI  - Isoflurane blocks temporary tinnitus.
AB  - Temporary tinnitus is a common consequence of noise exposure, and may share
      important mechanisms with chronic tinnitus. Noise-induced hearing loss is the
      most prevalent cause of chronic tinnitus. The reversibility of temporary tinnitus
      offers some practical experimental advantages. We therefore adapted a behavioral
      method based on gap detection to measure temporary tinnitus following brief
      acoustic trauma. Although anesthesia is often used during acoustic trauma
      exposure, many anesthetics can protect against noise-induced hearing loss.
      Whether anesthesia during acoustic trauma affects temporary tinnitus therefore
      remains an open question that directly affects experimental design in tinnitus
      studies. Here we tested whether anesthetizing rats with isoflurane during trauma
      had any effect on tinnitus. We found that gap-detection deficits, a behavioral
      measure of tinnitus, were 5 times stronger and lasted 10 times longer when
      isoflurane was not used. This suggests that isoflurane largely prevents temporary
      noise-induced tinnitus.

PMID- 22633942
TI  - Deiters cells tread a narrow path--the Deiters cells-basilar membrane junction.
AB  - Deiters cells extend from the basilar membrane to the reticular lamina and,
      together with pillar cells and outer hair cells, structurally define the micro
      architecture of the organ of Corti. Studying vibrotome sections of the mouse
      organ of Corti with confocal and scanning electron microscopy we found that the
      basal pole of every Deiters cell, independently of their position in the organ of
      Corti and along the cochlear spiral, attached to the basilar membrane within a
      15.1 +/- 0.3 MUm-wide stripe running the length of the cochlear spiral adjacent
      to the row of outer pillar cells. All Deiters cells' basal poles had similar
      diameter and general morphology, and distributed on the stripe in a precise
      arrangement with a center-to-center distance of 7.1 +/- 0.3 MUm between neighbor
      cells of the same row and 5.9 +/- 0.4 MUm for neighbor cells in adjacent rows.
      Complete detachment of Deiters cells revealed an elliptical imprint on the top
      surface of the basilar membrane consisting of a smaller central structure with a
      very smooth surface surrounded by a rougher area, suggesting the presence of two
      different anchoring junctions. These previously unidentified morphological
      features of Deiters cells could be critical for the mechanical response of the
      organ of Corti.

PMID- 22633943
TI  - Von Bekesy and cochlear mechanics.
AB  - Georg Bekesy laid the foundation for cochlear mechanics, foremost by
      demonstrating the traveling wave that is the substrate for mammalian cochlear
      mechanical processing. He made mechanical measurements and physical models in
      order to understand that fundamental cochlear response. In this tribute to Bekesy
      we make a bridge between modern traveling wave observations and those of Bekesy,
      discuss the mechanical properties and measurements that he considered to be so
      important, and touch on the range of computational traveling wave models.

PMID- 22633945
TI  - Disruption of visuospatial and somatosensory functional connectivity in anorexia
      nervosa.
AB  - BACKGROUND: Although body image disturbance is considered one of the core
      characteristics of anorexia nervosa (AN), the exact nature of this complex
      feature is poorly understood. Task-related functional magnetic resonance imaging
      studies can only partially explore the multimodal complexity of body
      consciousness, which is a complex cognition underpinned by aspects of visual
      perception, proprioception, and touch. The aim of the present study was to
      explore the functional connectivity of networks involved in visuospatial and
      somatosensory processing in AN. METHODS: Twenty-nine subjects with AN, 16 women
      who had recovered from it, and 26 healthy women underwent a resting-state
      functional magnetic resonance imaging scan and neuropsychological assessment of
      their visuospatial abilities using the Rey-Osterrieth Complex Figure Test.
      RESULTS: Both AN groups showed areas of decreased connectivity in the ventral
      visual network, a network involved in the "what?" pathway of visual perception.
      Even more interestingly, the AN group, but not the recovered AN group, displayed
      increased coactivation in the left parietal cortex, encompassing the
      somatosensory cortex, in an area implicated in long-term multimodal spatial
      memory and representation, even in the absence of visual information. A
      neuropsychological assessment of visuospatial abilities revealed that aspects of
      detail processing and global integration (central coherence) showed correlations
      with connectivity of this brain area in the AN group. CONCLUSIONS: Our findings
      show that AN is associated with double disruption of brain connectivity, which
      shows a specific association with visuospatial difficulties and may explain the
      failure of the integration process between visual and somatosensory perceptual
      information that might sustain body image disturbance.

PMID- 22633944
TI  - Progress in cochlear physiology after Bekesy.
AB  - In the fifty years since Bekesy was awarded the Nobel Prize, cochlear physiology
      has blossomed. Many topics that are now current are things Bekesy could not have
      imagined. In this review we start by describing progress in understanding the
      origin of cochlear gross potentials, particularly the cochlear microphonic, an
      area in which Bekesy had extensive experience. We then review progress in areas
      of cochlear physiology that were mostly unknown to Bekesy, including: (1)
      stereocilia mechano-electrical transduction, force production, and response
      amplification, (2) outer hair cell (OHC) somatic motility and its molecular basis
      in prestin, (3) cochlear amplification and related micromechanics, including the
      evidence that prestin is the main motor for cochlear amplification, (4) the
      influence of the tectorial membrane, (5) cochlear micromechanics and the
      mechanical drives to inner hair cell stereocilia, (6) otoacoustic emissions, and
      (7) olivocochlear efferents and their influence on cochlear physiology. We then
      return to a subject that Bekesy knew well: cochlear fluids and standing currents,
      as well as our present understanding of energy dependence on the lateral wall of
      the cochlea. Finally, we touch on cochlear pathologies including noise damage and
      aging, with an emphasis on where the field might go in the future.

PMID- 22633946
TI  - Genome-wide linkage analysis of obsessive-compulsive disorder implicates
      chromosome 1p36.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) has a complex etiology involving
      both genetic and environmental factors. However, the genetic causes of OCD are
      largely unknown, despite the identification of several promising candidate genes
      and linkage regions. METHODS: Our objective was to conduct genetic linkage
      studies of the type of OCD thought to have the strongest genetic etiology (i.e.,
      childhood-onset OCD), in 33 Caucasian families with >=2 childhood-onset OCD
      affected individuals from the United States (n = 245 individuals with genotype
      data). Parametric and nonparametric genome-wide linkage analyses were conducted
      with Morgan and Merlin in these families using a selected panel of single
      nucleotide repeat polymorphisms from the Illumina 610-Quad Bead Chip. The initial
      analyses were followed by fine-mapping analyses in genomic regions with initial
      heterogeneity logarithm of odds (HLOD) scores of >=2.0. RESULTS: We identified
      five areas of interest (HLOD score >=2) on chromosomes 1p36, 2p14, 5q13, 6p25,
      and 10p13. The strongest result was on chromosome 1p36.33-p36.32 (HLOD = 3.77,
      suggestive evidence for linkage after fine mapping). At this location, several of
      the families showed haplotypes co-segregating with OCD. CONCLUSIONS: The results
      of this study represent the strongest linkage finding for OCD in a primary
      analysis to date and suggest that chromosome 1p36, and possibly several other
      genomic regions, may harbor susceptibility loci for OCD. Multiple brain-expressed
      genes lie under the primary linkage peak (approximately 4 megabases in size).
      Follow-up studies, including replication in additional samples and targeted
      sequencing of the areas of interest, are needed to confirm these findings and to
      identify specific OCD risk variants.

PMID- 22633947
TI  - Altered development of the dorsolateral prefrontal cortex in chromosome 22q11.2
      deletion syndrome: an in vivo proton spectroscopy study.
AB  - BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11DS), the most common
      microdeletion in humans, is associated with multiple medical features, almost
      universal cognitive deficits, and a high risk of schizophrenia. The metabolic
      basis of the psychological/psychiatric features is not well understood.
      Volumetric brain imaging studies have shown that gray matter abnormalities in the
      dorsolateral prefrontal cortex (DLPFC), an area that is believed to be integral
      for higher neurocognition, as well as being involved in schizophrenia, are
      associated with the psychological manifestations. However, studies have not
      characterized any possible metabolite alterations within the DLPFC of children
      with 22q11DS and their correlations with the psychological findings. METHODS: We
      conducted a short echo time, single-voxel, in vivo proton spectroscopy study
      involving children with 22q11DS (n = 26) and matched control subjects (n = 23).
      RESULTS: Absolute N-acetylaspartate (NAA) levels from the DLPFC were
      significantly elevated in children with 22q11DS compared with control subjects
      and the elevations were associated with poor global functioning and higher rates
      of comorbid attention-deficit/hyperactivity disorder. Children with 22q11DS had a
      lack of an age-associated decrease in NAA levels, a trend seen in the control
      subjects. However, the results did not remain statistically significant after
      corrections for multiple comparisons were made. CONCLUSIONS: These findings
      represent the first report of proton spectroscopy in children with 22q11DS. The
      elevated DLPFC NAA levels and the lack of decreasing trends in NAA with age in
      the 22q11DS group relative to control subjects suggest an alteration in cortical
      development. Also, such neuronal dysmaturation is associated with psychopathology
      in children with 22q11DS.

PMID- 22633948
TI  - Activating mitochondrial regulator PGC-1alpha expression by astrocytic NGF is a
      therapeutic strategy for Huntington's disease.
AB  - Mitochondrial dysfunction plays an important role in Huntington's disease (HD).
      NGF gene delivery in AD patients showed an increase in brain energy metabolism
      and NGF has been shown neuroprotective effects against mitochondrial toxins.
      However, the role of NGF in regulating mitochondrial function is unclear. Here,
      we found that NGF-stimulated mitochondrial biogenesis in PC12 and primary neuron
      cells. Our results demonstrated that peroxisome proliferator-activated receptor
      gamma coactivator 1-alpha (PGC-1alpha) is a downstream key target of the NGF
      signalling pathway. In a 3-nitropropionic acid (3-NP) cell model, NGF treatment
      rescued the defects in mitochondrial activity and mitochondrial membrane
      potential. Since NGF cannot freely cross blood-brain barrier, we found an
      astrocytic NGF inducer, Ganoderma lucidum (GaLu) extract. Its active constituents
      had potent effects on the induction of NGF in primary astrocytes. Among the
      identified ingredients, ganoderic acid C2 was most effective. We further found
      that GaLu-conditioned media can enhance mitochondrial biogenesis in PC12 cells
      and preventing NGF signalling using NGF antibody or PGC-1alpha siRNA blocked
      these effects. Moreover, GaLu and ganoderic acid C2-conditioned media treatment
      attenuated mitochondrial defects in 3-NP cell model. After 3-NP-induced
      behavioural impairment and striatal degeneration in mice, GaLu treatment
      therapeutically restored the behaviour score, sensorimotor ability and neuronal
      loss. We found that striatal NGF, PGC-1alpha expression level and succinate
      dehydrogenase activity were recovered in GaLu-fed mice. These results suggest
      that the NGF-signalling pathway connected to the mitochondrial regulator, PGC
      1alpha, expression. This signalling triggered by astrocytic NGF with small
      molecule inducers may offer a therapeutic strategy for HD.

PMID- 22633950
TI  - Influence of anxiety in spatial memory impairments related to the loss of
      vestibular function in rat.
AB  - It is now well established that vestibular information plays an important role in
      spatial memory processes. Although vestibular lesions induce anxiety in humans,
      this finding remains controversial in rodents. However, it is possible that
      anxiety-related behavior is associated with spatial memory impairments after
      vestibular lesions. We aimed to evaluate anxiety-like behavior and the effect of
      an anxiolytic treatment during a complex spatial memory task in a rat model of
      compensated bilateral vestibular lesions. Adult rats were divided into four
      groups, with or without vestibular lesions and, treated or untreated by diazepam.
      The vestibular lesion was performed by transtympanic injection of arsanilate and
      compared to transtympanic saline injection. Diazepam or saline was administered
      1h before each test or learning session. Vestibular-lesioned rats exhibited
      anxiety-like behavior which was decreased with diazepam. Spatial memory
      performance was similar in control-treated and untreated groups, suggesting no
      effect on memory at the dose of diazepam used. Spatial memory performances were
      not modified by anxiolytic drug treatment in vestibular-lesioned rats compared to
      vestibular-lesioned rats without drug treatment. We conclude that bilateral
      vestibular lesions in rats induced anxiety-like behavior which was unrelated to
      spatial memory impairment and was probably specifically related to the loss of
      vestibular information.

PMID- 22633949
TI  - Dysregulation of synaptic proteins, dendritic spine abnormalities and
      pathological plasticity of synapses as experience-dependent mediators of
      cognitive and psychiatric symptoms in Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant tandem repeat expansion
      disorder involving cognitive, psychiatric and motor symptoms. The expanded
      trinucleotide (CAG) repeat leads to an extended polyglutamine tract in the
      huntingtin protein and a subsequent cascade of molecular and cellular
      pathogenesis. One of the key features of neuropathology, which has been shown to
      precede the eventual loss of neurons in the cerebral cortex, striatum and other
      areas, are changes to synapses, including the dendritic protrusions known as
      spines. In this review we will focus on synapse and spine pathology in HD,
      including molecular and experience-dependent aspects of pathogenesis. Dendritic
      spine pathology has been found in both the human HD brain at post mortem as well
      as various transgenic and knock-in animal models. These changes may help explain
      the symptoms in HD, and synaptopathy within the cerebral cortex may be
      particularly important in mediating the psychiatric and cognitive manifestations
      of this disease. The earliest stages of synaptic dysfunction in HD, as assayed in
      various mouse models, appears to involve changes in synaptic proteins and
      associated physiological abnormalities such as synaptic plasticity deficits. In
      mouse models, synaptic and cortical plasticity deficits have been directly
      correlated with the onset of cognitive deficits, implying a causal link.
      Furthermore, following the discovery that environmental enrichment can delay
      onset of affective, cognitive and motor deficits in HD transgenic mice, specific
      synaptic molecules shown to be dysregulated by the polyglutamine-induced toxicity
      were also found to be beneficially modulated by environmental stimulation. This
      identifies potential molecular targets for future therapeutic developments to
      treat this devastating disease. 

PMID- 22633951
TI  - Plasmodium ovale in Bangladesh: genetic diversity and the first known evidence of
      the sympatric distribution of Plasmodium ovale curtisi and Plasmodium ovale
      wallikeri in southern Asia.
AB  - In spite of the high prevalence of malaria in Bangladesh and other southern Asian
      countries, there remains a substantial shortage of knowledge about the less
      common human malaria parasites. Recent studies indicate that Plasmodium ovale is
      made up of two species, namely Plasmodium ovale wallikeri and Plasmodium ovale
      curtisi. Genus- and species-specific nested PCR analyses of the ssrRNA gene was
      used to detect P. ovale infections among 2,246 diagnostic samples. Plasmodium
      ovale infections were further differentiated by nested PCR of the potra gene and
      multilocus sequence analysis of the cox1, porbp2 and the ssrRNA genes. Both P.
      ovale curtisi and P. ovale wallikeri occur sympatrically in the Chittagong Hill
      Tracts, Bangladesh and all patients presented with a mild or asymptomatic symptom
      complex at the time of diagnosis. The pathogens can be differentiated by nested
      PCRs targeting the ssrRNA and potra genes, and display dimorphism in multilocus
      sequence analyses. We believe that we report the first evidence of sympatric P.
      ovale curtisi and P. ovale wallikeri in southern Asia within a relatively
      confined study area of less than 5,000 km(2). High rates of mixed infections, the
      emergence of "new" human malaria parasite species and the evidence of zoonotic
      capability call for optimised diagnostic strategies for a new era of eradication.

PMID- 22633952
TI  - Cryptosporidium viatorum n. sp. (Apicomplexa: Cryptosporidiidae) among travellers
      returning to Great Britain from the Indian subcontinent, 2007-2011.
AB  - A novel Cryptosporidium genotype was identified, among travellers with gastro
      intestinal symptoms returning to Great Britain from the Indian subcontinent, for
      which we propose the name Cryptosporidium viatorum n. sp. The epidemiology of
      these cases was distinctly different from those with Cryptosporidium parvum and
      Cryptosporidium hominis. Of the 10 cases identified involving C. viatorum, most
      were in the first quarter of the year. One occurred in 2007, one in 2008, three
      in 2010 and five to end March 2011. The median age was 19 years but most were in
      the 20-29 years age group and seven were male. The symptoms included diarrhoea,
      abdominal pain, nausea, vomiting and fever. Compared with cases due to C. hominis
      and C. parvum, vomiting was reported less often, although the duration of gastro
      intestinal symptoms was longer. The cases of C. viatorum were all travellers to
      the Indian subcontinent, whereas cases of C. hominis and C. parvum were more
      likely to have travelled elsewhere. Cryptosporidium viatorum isolates had
      indistinguishable sequences at each of the 70 kDa heat shock protein (HSP70),
      actin and ssrRNA loci which did not match any published previously and, although
      phylogenetically most similar to Cryptosporidium fayeri, they were distinct (<98%
      similarity) at the ssrRNA, HSP70 and actin genes. Morphologically, oocysts were
      typical of predominantly human-infecting species. Cryptosporidium viatorum n. sp.
      is proposed and work is warranted to investigate further the public health
      significance and occurrence elsewhere of this emerging parasite.

PMID- 22633953
TI  - NEMO ensures signaling specificity of the pleiotropic IKKbeta by directing its
      kinase activity toward IkappaBalpha.
AB  - Besides activating NFkappaB by phosphorylating IkappaBs, IKKalpha/IKKbeta kinases
      are also involved in regulating metabolic insulin signaling, the mTOR pathway,
      Wnt signaling, and autophagy. How IKKbeta enzymatic activity is targeted to
      stimulus-specific substrates has remained unclear. We show here that NEMO, known
      to be essential for IKKbeta activation by inflammatory stimuli, is also a
      specificity factor that directs IKKbeta activity toward IkappaBalpha. Physical
      interaction and functional competition studies with mutant NEMO and IkappaB
      proteins indicate that NEMO functions as a scaffold to recruit IkappaBalpha to
      IKKbeta. Interestingly, expression of NEMO mutants that allow for IKKbeta
      activation by the cytokine IL-1, but fail to recruit IkappaBs, results in
      hyperphosphorylation of alternative IKKbeta substrates. Furthermore IKK's
      function in autophagy, which is independent of NFkappaB, is significantly
      enhanced without NEMO as IkappaB scaffold. Our work establishes a role for
      scaffolds such as NEMO in determining stimulus-specific signal transduction via
      the pleiotropic signaling hub IKK.

PMID- 22633954
TI  - mRNA decay factor AUF1 maintains normal aging, telomere maintenance, and
      suppression of senescence by activation of telomerase transcription.
AB  - Inflammation is associated with DNA damage, cellular senescence, and aging.
      Cessation of the inflammatory cytokine response is mediated in part through
      cytokine mRNA degradation facilitated by RNA-binding proteins, including AUF1. We
      report a major function of AUF1-it activates telomerase expression, suppresses
      cellular senescence, and maintains normal aging. AUF1-deficient mice undergo
      striking telomere erosion, markedly increased DNA damage responses at telomere
      ends, pronounced cellular senescence, and rapid premature aging that increases
      with successive generations, which can be rescued in AUF1 knockout mice and their
      cultured cells by resupplying AUF1 expression. AUF1 binds and strongly activates
      the transcription promoter for telomerase catalytic subunit Tert. In addition to
      directing inflammatory cytokine mRNA decay, AUF1 destabilizes cell-cycle
      checkpoint mRNAs, preventing cellular senescence. Thus, a single gene, AUF1,
      links maintenance of telomere length and normal aging to attenuation of
      inflammatory cytokine expression and inhibition of cellular senescence.

PMID- 22633955
TI  - The Stat3/GR interaction code: predictive value of direct/indirect DNA
      recruitment for transcription outcome.
AB  - Transcription factor recruitment to genomic sites of action is primarily due to
      direct protein:DNA interactions. The subsequent recruitment of coregulatory
      complexes leads to either transcriptional activation or repression. In contrast
      to this canonical scheme, some transcription factors, such as the glucocorticoid
      receptor (GR), behave as transcriptional repressors when recruited to target
      genes through protein tethering. We have investigated the genome-wide prevalence
      of tethering between GR and Stat3 and found nonreciprocal interactions, namely
      that GR tethering to DNA-bound Stat3 results in transcriptional repression,
      whereas Stat3 tethering to GR results in synergism. Further, other schemes of GR
      and Stat3 corecruitment to regulatory modules result in transcriptional
      synergism, including neighboring and composite binding sites. The results
      indicate extensive transcriptional interactions between Stat3 and GR; further,
      they provide a genome-wide assessment of transcriptional regulation by tethering
      and a molecular basis for integration of signals mediated by GR and Stats in
      health and disease.

PMID- 22633956
TI  - Taz1 enforces cell-cycle regulation of telomere synthesis.
AB  - The dramatic telomerase-dependent overelongation of telomeres in cells lacking
      Taz1 (ortholog of human TRF1/TRF2) or Rap1 implicates these proteins in restraint
      of telomerase activity. However, the modes by which these proteins regulate
      telomerase remain mysterious. Here we show that the mechanisms underlying
      excessive telomerase activity differ markedly between taz1Delta and rap1Delta
      strains. Despite allowing elevated telomerase access, rap1Delta telomeres are
      processed and synthesized in a cell-cycle-constrained manner similar to that of
      wild-type cells. In contrast, taz1Delta telomeres are processed with little cell
      cycle dependency and recruit telomerase over an abnormally wide range of cell
      cycle stages. Furthermore, although taz1Delta telomeres experience transient
      attrition mediated by replication fork stalling, this is balanced not only by
      temporal expansion of the telomerase activity period, but also by markedly
      increased recruitment of telomerase and its accessory factor Est1, suggesting
      that stalled forks generate robust substrates for telomerase.

PMID- 22633957
TI  - Temporal coding of insulin action through multiplexing of the AKT pathway.
AB  - One of the unique characteristics of cellular signaling pathways is that a common
      signaling pathway can selectively regulate multiple cellular functions of a
      hormone; however, this selective downstream control through a common signaling
      pathway is poorly understood. Here we show that the insulin-dependent AKT pathway
      uses temporal patterns multiplexing for selective regulation of downstream
      molecules. Pulse and sustained insulin stimulations were simultaneously encoded
      into transient and sustained AKT phosphorylation, respectively. The downstream
      molecules, including ribosomal protein S6 kinase (S6K), glucose-6-phosphatase
      (G6Pase), and glycogen synthase kinase-3beta (GSK3beta) selectively decoded
      transient, sustained, and both transient and sustained AKT phosphorylation,
      respectively. Selective downstream decoding is mediated by the molecules' network
      structures and kinetics. Our results demonstrate that the AKT pathway can
      multiplex distinct patterns of blood insulin, such as pulse-like additional and
      sustained-like basal secretions, and the downstream molecules selectively decode
      secretion patterns of insulin.

PMID- 22633958
TI  - Role of the SEL1L:LC3-I complex as an ERAD tuning receptor in the mammalian ER.
AB  - Several regulators of endoplasmic reticulum (ER)-associated degradation (ERAD)
      have a shorter half-life compared to conventional ER chaperones. At steady state,
      they are selectively removed from the ER by poorly defined events collectively
      referred to as ERAD tuning. Here we identify the complex comprising the type-I
      transmembrane protein SEL1L and the cytosolic protein LC3-I as an ERAD tuning
      receptor regulating the COPII-independent, vesicle-mediated removal of the
      lumenal ERAD regulators EDEM1 and OS-9 from the ER. Expression of folding
      defective polypeptides enhances the lumenal content of EDEM1 and OS-9 by
      inhibiting their SEL1L:LC3-I-mediated segregation. This raises ERAD activity in
      the absence of UPR-induction. The mouse hepatitis virus (MHV) subverts ERAD
      tuning for replication. Consistently, SEL1L or LC3 silencing impair the MHV life
      cycle. Collectively, our data provide new molecular information about the ERAD
      tuning mechanisms that regulate ERAD in mammalian cells at the post translational
      level and how these mechanisms are hijacked by a pathogen.

PMID- 22633959
TI  - Therapies in inborn errors of oxidative metabolism.
AB  - Mitochondrial diseases encompass a wide range of presentations and mechanisms,
      dictating a need to consider both broad-based and disease-specific therapies. The
      manifestations of mitochondrial dysfunction and the response to therapy vary
      between individuals. This probably reflects the genetic complexity of
      mitochondrial biology, which requires an excess of 2000 genes for proper
      function, with numerous interfering epigenetic and environmental factors.
      Accordingly, we are increasingly aware of the complexity of these diseases which
      involve far more than merely decreased ATP supply. Indeed, recent therapeutic
      progress has addressed only specific disease entities. In this review present and
      prospective therapeutic approaches will be discussed on the basis of targets and
      mechanism of action, but with a broad outlook on their potential applications.

PMID- 22633960
TI  - Facilitated extinction of morphine conditioned place preference with Tat
      GluA2(3Y) interference peptide.
AB  - Neuroplasticity including long-term depression (LTD) has been implicated in both
      learning processes and addiction. LTD can be blocked by intravenous
      administration of the interference peptide Tat-GluA2(3Y) that prevents regulated
      endocytosis of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid
      (AMPA) receptor. In this study, Tat-GluA2(3Y) was used to assess the role of LTD
      in the induction, expression, extinction and reinstatement of morphine-induced
      conditioned place preference (CPP). CPP was established in rats by pairing
      morphine (5 mg/kg, i.p.) or saline with a specific environmental context using a
      balanced protocol. Tat-GluA2(3Y) (0; 1.5; 2.25 nmol/g; i.v.), scrambled peptide
      (Tat-GluA2(Sc)), or vehicle was administered during the acquisition phase or
      prior to the test for CPP. Tat-GluA2(3Y) had no effect on the induction or
      initial expression of morphine-induced CPP. Rats that received Tat-GluA2(3Y) or
      Tat-GluA2(Sc) during acquisition were subsequently tested for 11 consecutive days
      in order to extinguish morphine CPP. CPP was then reinstated by an injection of
      morphine (5 mg/kg, i.p.). Co-administration of morphine and Tat-GluA2(3Y) during
      acquisition greatly facilitated extinction of CPP without affecting morphine
      induced reinstatement of CPP. Using an intermittent retest schedule with bi
      weekly tests to measure the maintenance of CPP, Tat-GluA2(3Y) during the
      acquisition phase had no effect on the maintenance of CPP. We propose that co
      administration of Tat-GluA2(3Y) with morphine during acquisition of CPP weakens
      the association between morphine and contextual cues leading to rapid extinction
      of morphine CPP with repeated daily testing.

PMID- 22633961
TI  - Comparison of nicotine oral consumption and baseline anxiety measures in
      adolescent and adult C57BL/6J and C3H/Ibg mice.
AB  - Approximately 80% of smokers initiate tobacco use during adolescence, suggesting
      that nicotine initiation and nicotine dependence have a substantial age
      component. There also is a substantial genetic influence on smoking behaviors
      such as age of initiation and the development of nicotine dependence. The goal of
      this study was to examine both genetic background and age dependent effects on
      oral nicotine self-administration and anxiety-like behaviors in mice. Two inbred
      mouse strains (C3H/Ibg and C57BL/6J) were assessed for oral nicotine preference
      during early adolescence (postnatal day 24-35), middle adolescence (postnatal day
      36-47), late adolescence (postnatal day 48-59), adulthood (postnatal day 60+) and
      2 months following their initial exposure to nicotine. Mice also were assessed
      for innate anxiety using an elevated zero maze to determine if age and/or genetic
      background influenced anxiety-like behaviors. Results indicated that initial
      nicotine preference and nicotine preference two months after an initial exposure
      are both strain and age dependent. Age also had an effect on some baseline
      anxiety measures but strain differences for most zero maze measures were present
      throughout all age groups. In general, early adolescent C3H mice exhibited
      greater nicotine preference while C57 mice displayed greater preference during
      middle adolescence and upon a second exposure to nicotine. In contrast, C57 mice
      exhibited reduced anxiety across all ages tested. These studies indicate that
      genetic background should be considered when evaluating age-dependent effects of
      drugs of abuse and baseline anxiety-like behaviors.

PMID- 22633962
TI  - Can zebrafish learn spatial tasks? An empirical analysis of place and single CS
      US associative learning.
AB  - The zebrafish may be an ideal tool with which genes underlying learning and
      memory can be identified and functionally investigated. From a translational
      viewpoint, relational learning and episodic memory are particularly important as
      their impairment is the hallmark of prevalent human neurodegenerative diseases.
      Recent reports suggest that zebrafish are capable of solving complex relational
      type associative learning tasks, namely spatial learning tasks. However, it is
      not known whether good performance in these tasks was truly based upon relational
      learning or upon a single CS-US association. Here we study whether zebrafish can
      find a rewarding stimulus (sight of conspecifics) based upon a single associative
      cue or/and upon the location of the reward using a method conceptually similar to
      'context and cue dependent fear conditioning' employed with rodents. Our results
      confirm that zebrafish can form an association between a salient visual cue and
      the rewarding stimulus and at the same time they can also learn where the reward
      is presented. Although our results do not prove that zebrafish form a dynamic
      spatial map of their surroundings and use this map to locate their reward, they
      do show that these fish perform similarly to rodents whose hippocampal function
      is unimpaired. These results further strengthen the notion that complex cognitive
      abilities exist in the zebrafish and thus they may be analyzed using the
      excellent genetic tool set developed for this simple vertebrate.

PMID- 22633963
TI  - N-arachidonoyl-serotonin in the basolateral amygdala increases anxiolytic
      behavior in the elevated plus maze.
AB  - CB(1) receptors in the amygdala have been shown to mediate learned and unlearned
      anxiety states, however, the role of amygdalar TRPV1 receptors remains unclear.
      In the present study we investigated the potential anxiolytic action of intra
      basolateral amygdala (BLA) infusion of N-arachidonoyl-serotonin (AA-5-HT), a dual
      blocker of the endocannabinoid-inactivating enzyme, fatty acid amide hydrolase
      (FAAH), and a TRPV1 antagonist. Varying doses of AA-5-HT (0-0.5 nmol) were
      administered into the BLA prior to elevated plus maze testing. AA-5-HT
      significantly increased both time spent and number of entries into the open arms.
      Next, to determine whether the anxiolytic effects were the result of blocking
      FAAH, TRPV1, or whether a combined action was required, rats were given intra-BLA
      infusions of either 0.25 nmol AA-5-HT, 1.0 nmol capsazepine (CZP, a TRPV1
      antagonist), 0.01 MUg URB597 (a selective FAAH inhibitor), or vehicle. Again, AA
      5-HT increased the time spent in the open arms as well as the number of open arm
      entries. In contrast, CZP and URB597 did not reliably alter plus maze
      performance. We then investigated the effects of co-administration of CZP (1.0 or
      10.0 nmol) and URB597 (0.01 or 0.1 MUg). At lower doses, co-injections
      significantly increased both open arm entries as well as the time spent in the
      open arms, compared to vehicle or either compound alone. While co-administration
      of the higher doses had no significant effect when compared to either vehicle or
      CZP treatment, we did observe that open arm activity was elevated in rats
      receiving combined CZP-URB597 treatment compared to URB597 alone. Overall, our
      findings indicate that simultaneous FAAH activity and TRPV1 activation are
      important with respect to the expression of unconditioned fear as mediated within
      the BLA.

PMID- 22633964
TI  - Assessment of the stochastic threshold, back- and forward stutter filters and low
      template techniques for NGM.
AB  - The AmpFlSTR((r)) NGMTM kit shows an increased sensitivity compared to previous
      AmpFlSTR((r)) kits, and the addition of a 29th PCR cycle was found to be the
      major cause for this. During in-house validation, we evaluated whether the
      increased sensitivity requires elevation of the stochastic threshold (below which
      alleles are prone to drop out due to low template amplification effects). To
      determine the stochastic threshold, over 500 false homozygotes were examined and
      the threshold was set at the rfu value where 99% of the alleles had a peak height
      below this value. Using 2085 Dutch reference samples, locus-specific stutter
      ratios were empirically determined and compared with the ones provided by Applied
      Biosystems. Application of sharp stutter filters is especially important for the
      analysis of unequal mixtures. To prevent allele calling of 99% of the -1 repeat
      unit stutters, thirteen stutter ratio filters could be lowered by up to 1.79% and
      for two loci the stutter ratio filters had to be elevated slightly with a maximum
      of 0.06%. At all loci +1 repeat stutters were visible for the higher DNA inputs
      and for lower inputs at the tri-nucleotide repeat locus D22S1045 as well. The
      overall +1 stutter ratio filter was set to 2.50% and for D22S1045 it was
      determined to be 7.27%. To find the optimal strategy to sensitise genotyping for
      low template DNA samples, a comparison was made between enhancing the capillary
      electrophoresis settings (9kV for 10s) and increasing the number of PCR cycles
      (29+5 cycles).

PMID- 22633965
TI  - Quantification of retinal tangential movement in epiretinal membranes.
AB  - OBJECTIVE: To describe a technique of quantifying retinal vessel movement in eyes
      with epiretinal membrane (ERM) and correlate the retinal vessel movement with
      changes in best-corrected visual acuity (BCVA), central macular thickness (CMT),
      and patients' subjective reports about experienced symptoms (symptoms). DESIGN:
      Retrospective, observational, comparative case series. PARTICIPANTS: A total of
      206 eyes of 113 patients: 142 eyes with ERM and 64 healthy fellow eyes. METHODS:
      All patients were examined as part of a screening protocol for a randomized
      clinical trial on ERM. Heidelberg Spectralis (Heidelberg Engineering Inc,
      Carlsbad, CA) optical coherence tomography (OCT) scanning had been performed
      twice or more in all patients. Eyes with ERM and healthy fellow eyes were
      examined. For each eye, the 2 fundus images were aligned using Heidelberg's
      AutoRescan feature. The macular area was divided into 9 subfields, and retinal
      vessel movements were calculated. For each eye, the total length of the 9 vectors
      was summed to describe the total retinal vessel movement (retinal tangential
      movement [RTM]). MAIN OUTCOME MEASURES: To quantify retinal vessel movements
      associated with ERM. The secondary outcome was to correlate measured retinal
      vessel movement with changes in BCVA, CMT, and patients' subjective symptoms.
      RESULTS: The study found significantly greater RTM in ERM eyes compared with
      healthy eyes (P<0.001). Among ERM eyes, the RTM was significantly greater in
      patients with worsening of symptoms compared with ERM eyes with unchanged
      assessment of symptoms. There were statistically significant correlations between
      increased RTM and reduction in BCVA (P = 0.024), increased CMT (P<0.001), and
      time between visits (P<0.001). CONCLUSIONS: This study showed that ERM is not a
      static retinal disease but a dynamic condition in which retinal vessel movement
      associated with ERM was measureable, even in patients who had stable BCVA and
      CMT. The retinal vessel movements correlated to worsening of BCVA and increased
      CMT, and were more pronounced in patients with worsening of symptoms.

PMID- 22633966
TI  - Characterization of Pseudomonas mendocina LR capable of removing nitrogen from
      various nitrogen-contaminated water samples when cultivated with Cyperus
      alternifolius L.
AB  - A new strain of denitrifying bacterium, Pseudomonas mendocina LR, was isolated
      from rhizosphere soil of aquatic plants living in a river contaminated with
      industrial wastewater and domestic sewage. The isolate was found to fully remove
      as much as 613.2 mg nitrate in 60 h under stationary culture conditions. The
      effects of carbon sources and nitrogen sources on nitrogen removal were
      investigated using a modified denitrification medium (DM). Sodium citrate was
      identified as the most effective source of carbon. The ability of LR to adapt to
      different nitrogen sources, including nitrite, indicated that LR could be used in
      the purification of wastewater containing different forms of nitrogen. The
      optimal C/N ratio was 7 for LR, and it was resistant to antibiotics Amp, Chl,
      Ery, and Str. Plant-microbe bioaugmentation was performed to remove nitrogen
      dissolved in Hoagland medium and natural wastewater. An increased rate of
      nitrogen removal was observed when root exudates of Cyperus alternifolius L. were
      added simultaneously with LR. LR was not able to survive in the natural
      wastewater unless root exudates from umbrella grass were added. LR cultured with
      umbrella grass exhibited a maximal nitrogen reduction rate of 95.9% and 97.3% in
      Hoagland medium and wastewater, respectively. This shows that bioaugmentation
      utilizing plant-microbe interactions can be an effective and exhaustive means of
      removing nitrogen and may be an attractive approach to nitrogen reduction in
      natural environments and wastewater treatment factories.

PMID- 22633967
TI  - Preventive and curative effect of Trigonella foenum-graecum L. seeds in C57BL/6J
      models of type 2 diabetes induced by high-fat diet.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Trigonella foenum-graecum L. (TFG) is
      traditionally used to treat diabetes in North Africa. we therefore tested the
      effects of the hydro-alcoholic extract of TFG seeds in a C57/BL6J mouse model of
      diabetes induced by a standardised high-fat diet (HFD). MATERIALS AND METHODS:
      Plant extracts (2 g/kg daily) were administered orally by gavage at the start of
      HFD, or after confirmation of established diabetes (17th week), for 20 or 18
      weeks, respectively, to male C57BL/6J mice. Animals were weighed; food intake and
      plasma glucose, lipid profile, insulin and insulin resistance were measured.
      RESULTS: TFG extracts opposed the development of diabetes: compared with
      untreated HFD mice, TFG-treated HFD mice had lower mean (+/- SD) plasma glucose
      (129.3 +/- 39.4 vs. 183.1 +/- 19.1mg/dL, p<0.05), plasma insulin (1.3 +/- 0.8 vs.
      3.1 +/- 1.8 ng/mL, p<0.05) and triglycerides (18.9 +/- 12.9 vs. 48.9 +/-
      12.1mg/dL, p<0.05), and less insulin resistance as estimated by the homeostasis
      model assessment (HOMA: 9.7 +/- 11.1 vs. 38.3 +/- 26.6, p<0.05). In mice with
      established diabetes, TFG reduced fasting plasma glucose (170.4 +/- 24.1 vs.
      229.0 +/- 20.8 mg/dL, p<0.05), plasma insulin (1.7 +/- 1.3 vs. 3.3 +/- 14.3
      ng/mL, p<0.05) and insulin resistance (HOMA: TFG: 19.2 +/- 15.7 vs. HFD control:
      38.5 +/- 30.3, p<0.05). In addition, administration of TFG extract also caused
      significant reduction in triglycerides (17.9 +/- 9.7 vs. 62.8 +/- 18.3 mg/dL,
      p<0.05) and total cholesterol (1.30 +/- 0.20 vs. 1.80 +/- 1.10 g/L, p<0.05), and
      an increase in HDL-cholesterol (1.6 +/- 0.2 vs. 1.2 +/- 0.1 g/L). The plant
      extract had no effect on calorie intake or body weight. CONCLUSION: TFG extract
      opposed the development of experimental HFD diabetes in mice, and had an anti
      diabetic effect in mice with established diabetes.

PMID- 22633968
TI  - Gene-activated and cell-migration guiding PEG matrices based on three dimensional
      patterning of RGD peptides and DNA complexes.
AB  - Essential to the design of genetic bioreactors used in the human body is a
      consideration of how the properties of biomaterials can combine to envelope,
      spatially guide, reprogramme by gene transfer, and then release cells. In order
      to approach this goal, poly(ethylene glycol) (PEG) matrices with modulated
      structural features and defined spatial patterns of bioactive signals have been
      designed and produced. In particular, within such PEG matrices, both an adhesive
      RGD peptide gradient, to directionally attract NIH3T3 cells, and a designed
      spatial distribution of immobilized poly(ethylenimine) (PEI)/DNA complexes, to
      obtain a localized transfection, have been realized. These bioactive biomaterials
      have been designed bearing in mind that cells following an RGD gradient migrate
      through the matrix, in which they find the bound DNA and become transfected. Both
      cell migration and transfection have been monitored by fluorescence microscopy.
      Results show that this system is able to envelope cells, spatially guide them
      towards the immobilized gene complexes and locally transfect them. Therefore, the
      system, acting as a genetic bioreactor potentially useful for the regulation of
      biology at a distance, could be used to directly control cell trafficking and
      activation in the human body, and has many potential biomedical applications.

PMID- 22633969
TI  - Healing of complement activating Ti implants compared with non-activating Ti in
      rat tibia.
AB  - Recent studies have revealed that ozone ultraviolet (UVO) illumination of
      titanium (Ti) implants improves bone-implant anchorage by altering the physico
      chemical and immune activating properties of the titanium dioxide (TiO(2)) layer.
      In the present rat tibia model, the authors compared the early events of
      inflammation and bone formation around UVO-treated Ti and complement activating
      immunoglobin g (IgG)-coated Ti. Machined Ti and machined Ti coated with a
      physical vapour-deposited Ti layer were used as references. Screw-shaped test and
      reference implants were implanted into rat tibia and harvested after 1, 7 and 28
      days. Messenger RNA expression of implant adhered cells and peri-implant tissue
      ~250 MUm from the surface were subsequently analysed with regard to IL-1beta, TNF
      alpha, osteocalcin, cathepsin K, BMP-2 and PDGF. Separate implants were retrieved
      after 7 and 28 days for removal torque measurements, and histological staining
      and histomorphometric analysis of bone area and bone-to-implant contact. While
      enhanced expression of inflammatory markers, TNF-alpha and IL-1beta, was observed
      on IgG-coated surfaces throughout the observation time, UVO-treated surfaces
      indicated a significantly lower early inflammatory response. In the early phases
      (1 and 7 days), the UVO-treated surfaces displayed a significantly higher
      expression of osteoblast markers BMP-2 and osteocalcin. In summary, complement
      activating Ti implants elicited a stronger inflammatory response than UVO-treated
      Ti, with low complement activation during the first week of healing. In spite of
      this, the UVO-treated Ti induced only marginally more bone growth outside the
      implants.

PMID- 22633971
TI  - PKC signaling inhibits osteogenic differentiation through the regulation of Msx2
      function.
AB  - Protein kinase C (PKC) signaling regulates osteoblast differentiation, but little
      is known about its downstream effectors. We examined the effect of modulating PKC
      activity on osteogenic transcription factors and found that the protein level of
      Msx2 is affected. Msx2 is induced by osteogenic signals such as BMPs and it plays
      critical roles in bone formation and osteoblast differentiation. Here, we
      examined the role of PKC signaling in regulating the function of Msx2. We found
      that the inhibition of PKC signaling enhances osteogenic differentiation in BMP2
      stimulated C2C12 cells. Treatment with inhibitors of PKC activity or
      overexpression of kinase-defective (KD), dominant-negative mutant PKC isoforms
      strongly reduced the level of Msx2 protein. Several PKC isoforms (alpha, beta,
      delta, and zeta) interacted with Msx2, and PKCbeta phosphorylated Msx2 at Thr135
      and Thr141. Msx2 repressed the transcriptional activity of the osteogenic
      transcription factor Runx2, and this repression was relieved by inhibition of PKC
      activity or overexpression of the KD mutant PKC isoforms. In addition, PKC
      prolonged the half-life of Msx2 protein. These results suggest that PKC signaling
      modulates osteoblast differentiation, at least in part, through the regulation of
      Msx2.

PMID- 22633970
TI  - Human embryonic stem cell encapsulation in alginate microbeads in macroporous
      calcium phosphate cement for bone tissue engineering.
AB  - Human embryonic stem cells (hESC) are promising for use in regenerative medicine
      applications because of their strong proliferative ability and multilineage
      differentiation capability. To date there have been no reports on hESC seeding
      with calcium phosphate cement (CPC). The objective of this study was to
      investigate hESC-derived mesenchymal stem cell (hESCd-MSC) encapsulation in
      hydrogel microbeads in macroporous CPC for bone tissue engineering. hESC were
      cultured to form embryoid bodies (EB), and the MSC were then migrated out of the
      EB. hESCd-MSC had surface markers characteristic of MSC, with positive alkaline
      phosphatase (ALP) staining when cultured in osteogenic medium. hESCd-MSC were
      encapsulated in alginate at a density of 1millioncellsml(-1), with an average
      microbead size of 207MUm. CPC contained mannitol porogen to create a porosity of
      64% and 218-MUm macropores, with 20% absorbable fibers for additional porosity
      when the fibers degrade. hESCd-MSC encapsulated in microbeads in CPC had good
      viability from 1 to 21days. ALP gene expression at 21days was 25-fold that at
      1day. Osteocalcin (OC) at 21days was two orders of magnitude of that at 1day. ALP
      activity in colorimetric p-nitrophenyl phosphate assay at 21days was fivefold
      that at 1day. Mineral synthesis by the encapsulated hESCd-MSC at 21days was
      sevenfold that at 1day. Potential benefits of the CPC-stem cell paste include
      injectability, intimate adaptation to complex-shaped bone defects, ease in
      contouring to achieve esthetics in maxillofacial repairs, and in situ setting
      ability. In conclusion, hESCd-MSC were encapsulated in alginate microbeads in
      macroporous CPC, showing good cell viability, osteogenic differentiation and
      mineral synthesis for the first time. The hESCd-MSC-encapsulating macroporous CPC
      construct is promising for bone regeneration in a wide range of orthopedic and
      maxillofacial applications.

PMID- 22633972
TI  - Inhibitory role of adiponectin peptide I on rat choroidal neovascularization.
AB  - Age-related macular degeneration (AMD) is a leading cause of central blindness in
      the elderly population. The wet type of AMD is characterized by extensive growth
      of new vessels. One of the effective strategies to treat wet AMD is to limit the
      choroidal neovascularization (CNV). We studied the effects of adiponectin peptide
      I (APNpI) on new vessel growth in laser-induced rat model of wet AMD and on rat
      choroidal endothelial cell (CEC) culture. CNV size and vessel density were
      investigated by microscopy. Immunohistochemical staining (IHC) for von Willebrand
      Factor (vWF), APN, APN receptors 1 (AdipoR1), 2 (AdipoR2), VEGF, VEGF receptor 2
      (VEGF-R2), proliferating cell nuclear antigen (PCNA) was performed in CNV area.
      The mRNA expression of VEGF and VEGF-R2 in RPE-choroid was investigated by RT-PCR
      and real-time PCR. APNpI inhibited area of CNV by 4 fold, number of vWF positive
      vessels by 99% and area of subretinal tissue by 40%. The expression of VEGF and
      VEGF-R2 at mRNA and protein levels decreased after APNpI treatment in vivo.
      Proliferative index (PCNA) was 5 folds less in laser spots of APNpI treated rats
      compared to controls. In conclusion, APNpI inhibited formation of new vessels in
      rat model of CNV by decreasing VEGF, VEGF-R2 expression and cell proliferation.
      Thus, APNpI may have potential therapeutic use for AMD treatment since it
      significantly inhibited CNV.

PMID- 22633974
TI  - Coalescent-based species delimitation in an integrative taxonomy.
AB  - The statistical rigor of species delimitation has increased dramatically over the
      past decade. Coalescent theory provides powerful models for population genetic
      inference, and is now increasingly important in phylogenetics and speciation
      research. By applying probabilistic models, coalescent-based species delimitation
      provides clear and objective testing of alternative hypotheses of evolutionary
      independence. As acquisition of multilocus data becomes increasingly automated,
      coalescent-based species delimitation will improve the discovery, resolution,
      consistency, and stability of the taxonomy of species. Along with other tools and
      data types, coalescent-based species delimitation will play an important role in
      an integrative taxonomy that emphasizes the identification of species limits and
      the processes that have promoted lineage diversification.

PMID- 22633973
TI  - Accelerating the pace of taxonomy.

PMID- 22633975
TI  - The C-terminus of human Ca(v)2.3 voltage-gated calcium channel interacts with
      alternatively spliced calmodulin-2 expressed in two human cell lines.
AB  - Ca(v)2.3 containing voltage-activated Ca(2+) channels are expressed in excitable
      cells and trigger neurotransmitter and peptide-hormone release. Their expression
      remote from the fast release sites leads to the accumulation of presynaptic
      Ca(2+) which can both, facilitate and inhibit the influx of Ca(2+) ions through
      Ca(v)2.3. The facilitated Ca(2+) influx was recently related to hippocampal
      postsynaptic facilitation and long term potentiation. To analyze Ca(2+) mediated
      modulation of cellular processes more in detail, protein partners of the carboxy
      terminal tail of Ca(v)2.3 were identified by yeast-2-hybrid screening, leading in
      two human cell lines to the detection of a novel, extended and rarely occurring
      splice variant of calmodulin-2 (CaM-2), called CaM-2-extended (CaM-2-ext). CaM-2
      ext interacts biochemically with the C-terminus of Ca(v)2.3 similar to the
      classical CaM-2 as shown by co-immunoprecipitation. Functionally, only CaM-2-ext
      reduces whole cell inward currents significantly. The insertion of the novel 46
      nts long exon and the consecutive expression of CaM-2-ext must be dependent on a
      new upstream translation initiation site which is only rarely used in the tested
      human cell lines. The structure of the N-terminal extension is predicted to be
      more hydrophobic than the remaining CaM-2-ext protein, suggesting that it may
      help to dock it to the lipophilic membrane surrounding.

PMID- 22633976
TI  - Molecular dynamics simulation study of the vanillate transport channel of Opdk.
AB  - Most water-soluble and small molecules are taken up by substrate-specific
      channels belonging to the Gram-negative bacteria. The protein named OpdK, a
      member of OprD family, plays an important role in transporting the vanillate as
      the only carbon source of Pseudomonas aeruginosa. P. aeruginosa infections can be
      serious due to the high intrinsic antibiotic resistance owing to the present of
      the OprD family. We applied standard molecular dynamics, steered molecular
      dynamics and umbrella sampling, to investigate the thermodynamics of vanillate
      passing through the pore of OpdK protein at physiological temperature. The
      results indicate that hydrogen bonds of vanillate-L3 (L3: Gly92-Gln111) and
      hydrophobic interactions of vanillate-L7 (Gly252-Asn278) are crucial to the
      transport of vanillate. Compared to L7, L3 can hardly change the shape of the
      pore, but its amino acids can effectively affect the transport process. The
      important role of charged residues in the barrel of the protein for the substrate
      transport has been proved in the experiment researches and our simulations also
      determinate that these residues may prevent the vanillate from entering the cell.
      These results provide detailed information that will facilitate the development
      of effective drugs.

PMID- 22633977
TI  - Resveratrol protects adult cardiomyocytes against oxidative stress mediated cell
      injury.
AB  - Recent studies from our laboratory have showed that resveratrol, a polyphenol
      found predominantly in grapes rendered strong cardioprotection in animal models
      of heart disease. The cardioprotection which was observed was primarily
      associated with the ability of resveratrol to reduce oxidative stress in these
      models. The aim of the current study was to corroborate the role of resveratrol
      as an inhibitor of oxidative stress and explore the underlying mechanisms of its
      action in heart disease. For this purpose, we used a cell model of oxidative
      stress, the hydrogen peroxide (H(2)O(2)) exposed adult rat cardiomyocytes, which
      was treated with and without resveratrol (30 MUM); cardiomyocytes which were not
      exposed to resveratrol served as controls. Cell injury, cell death and oxidative
      stress measurements as well as the activities of the major endogenous
      antioxidants superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GPx) were carried out in control and H(2)O(2) exposed cardiomyocytes,
      treated with and without resveratrol. Pharmacological blockade using specific
      blockers of the antioxidant enzymes were used to confirm their role in mediating
      resveratrol action in H(2)O(2) exposed cardiomyocytes. The status of H(2)O(2) and
      antioxidant enzymes in serum samples from spontaneously hypertensive rats (SHR)
      treated with and without resveratrol (2.5 mg/kg body weight) was also examined.
      Our results showed significant cell injury and death in H(2)O(2) exposed
      cardiomyocytes which was prevented upon resveratrol treatment. SOD and CAT
      activities were decreased in H(2)O(2) exposed adult rat cardiomyocytes; treatment
      with resveratrol significantly prevented this reduction. However, GPx activity
      was not altered in the H(2)O(2) exposed cardiomyocytes in comparison to controls.
      Pharmacological blockade of SOD and/or CAT prevented the beneficial effect of
      resveratrol. In SHR, H(2)O(2) levels were increased, but CAT activity was
      decreased, while SOD remained unchanged, when compared to WKY rats; resveratrol
      treatment significantly prevented the increase in H(2)O(2) levels and the
      decrease in CAT activities in SHR. Based on our results, we conclude that
      treatment with resveratrol prevents oxidative stress induced cardiomyocyte injury
      mainly by preserving the activities of critical antioxidant enzymes. This may be
      a crucial mechanism by which resveratrol confers cardioprotection.

PMID- 22633979
TI  - Noninvasive cortical modulation of experimental pain.
AB  - Noninvasive cortical stimulation (NICS) can produce analgesic effects by means of
      repetitive transcranial magnetic stimulation or transcranial direct current
      stimulation (tDCS). Such effects have been demonstrated on chronic ongoing pain,
      as in acute provoked pain. The investigation of induced changes in the perception
      of experimental pain by NICS could help clinicians and researchers to better
      understand the mechanisms of action involved with these techniques and the role
      played by the cortex in the integration of nociceptive information. This review
      presents current literature data on the modulation of experimental pain
      perception by cortical stimulation. The observations found that NICS analgesic
      effects depend on the method used to provoke pain (referring to the type of nerve
      fibers and neural circuits that are recruited to mediate pain) and the parameters
      of cortical stimulation (especially the nature of the cortical target). The motor
      cortex (precentral cortical area) is the most widely used target for pain
      modulation. However, other targets, such as the dorsolateral prefrontal cortex,
      could be of particular interest to modulate various components of pain. Further
      developments in NICS techniques, such as image-guided navigated brain
      stimulation, might lead to improvement in the beneficial effects of NICS on pain.
      Finally, we discuss whether the results obtained in experimental pain can be
      transposed to the problem of chronic pain and whether they can be used to
      optimize cortical stimulation therapy for pain disorders.

PMID- 22633978
TI  - Plasticity of cytochrome P450 isozyme expression in rat trigeminal ganglia
      neurons during inflammation.
AB  - Recently, specific oxidized linoleic acid metabolites (OLAMs) have been
      identified as transient receptor potential vanilloid 1 (TRPV1) channel agonists
      that contribute to inflammatory and heat hyperalgesia mechanisms, yet the
      specific mechanism responsible for OLAM synthesis in sensory neurons is unknown.
      Here, we use molecular, anatomical, calcium imaging, and perforated patch
      electrophysiology methods to demonstrate the specific involvement of cytochrome
      P450 enzymes (CYPs) in the oxidation of linoleic acid leading to neuronal
      activation and show that this is enhanced under inflammatory conditions.
      Additional studies evaluated CYP expressions in the native rat trigeminal ganglia
      (TG) tissue and cultures as well as changes in their expression pattern following
      the induction of peripheral inflammation. Fourteen of 20 candidate transcripts
      were detected in native TG, and 7 of these displayed altered expression under
      cultured conditions. Moreover, complete Freund's adjuvant-induced inflammation of
      vibrissal pad selectively increased expression of CYP3A23/3A1 and CYP2J4
      transcripts in TG. In situ hybridization studies demonstrated broad expression
      pattern of CYP3A23/3A1 and CYP2J4 within TG neurons. Anatomical studies
      characterized the expression of CYP3A1 and the CYP2J families within TG sensory
      neurons, including those with TRPV1, with about half of all TRPV1-positive
      neurons showing more prominent CYP3A1 and CYP2J expression. Together, these
      findings show that CYP enzymes play a primary role in mediating linoleic acid
      evoked activation of sensory neurons and furthermore, implicate the involvement
      of specific CYPs as contributing to the formation of OLAMs that act as TRPV1
      agonists within this subpopulation of nociceptors.

PMID- 22633981
TI  - Polyphenols in madhumega chooranam, a Siddha medicine, ameliorates carbohydrate
      metabolism and oxidative stress in type II diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Present study was undertaken to demonstrate the
      mode of anti-diabetic action of a polyherbal Siddha Medicine, Madhumega chooranam
      (MMC). MATERIALS AND METHODS: MMC was fractionated into phenolic (PMMC) and non
      phenolic (NPMMC) portions in order to identify bioactive fraction. Study was
      performed in type II diabetic rats. Role of PMMC and NPMMC on liver glucose-6
      phosphatase, fructose-1,6-bisphosphatase, glucokinase and glycogen content were
      determined. Their role on superoxide dismutase, reduced glutathione and lipid
      peroxidation were investigated. In addition, their effects on GLUT4 and PPARgamma
      gene expression were studied. Pancreas and liver histopathology was studied using
      hematoxylin and eosin stain. RESULTS: PMMC improved carbohydrate metabolism by
      decreasing glucose-6-phosphatase and fructose-1,6-bisphosphatase and increasing
      glucokinase and glycogen contents in diabetic rats liver. It alleviated oxidative
      stress by increasing superoxide dismutase, glutathione and decreasing lipid
      peroxidation content. PMMC up-regulated liver GLUT4 and PPARgamma mRNA expression
      in comparison to the vehicle or NPMMC rats. CONCLUSION: Madhumega chooranam
      mediates its anti-diabetic action through the inhibition of gluconeogenesis and
      activation of glycolytic pathways in type II diabetic rats. Increased GLUT4 and
      PPARgamma expressions provide additional information on its glucose
      uptake/sensitising and hypolipidemic potential. Phenolic components of MMC were
      found to be the bioactive principles.

PMID- 22633982
TI  - Nuciferine stimulates insulin secretion from beta cells-an in vitro comparison
      with glibenclamide.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Several Asian plants are known for their anti
      diabetic properties and produce alkaloids and flavonoids that may stimulate
      insulin secretion. MATERIALS AND METHODS: Using Vietnamese plants (Nelumbo
      nucifera, Gynostemma pentaphyllum, Smilax glabra, and Stemona tuberosa), we
      extracted two alkaloids (neotuberostemonine, nuciferine) and four flavonoids
      (astilbin, engeletin, smitilbin, and 3,5,3'-trihydroxy-7,4'-dimethoxyflavone),
      and studied their insulin stimulatory effects. RESULTS: Nuciferine, extracted
      from Nelumbo nucifera, stimulated both phases of insulin secretion in isolated
      islets, whereas the other compounds had no effect. The effect of nuciferine was
      totally abolished by diazoxide and nimodipine, and diminished by protein kinase A
      and protein kinase C inhibition. Nuciferine and potassium had additive effects on
      insulin secretion. Nuciferine also stimulated insulin secretion in INS-1E cells
      at both 3.3 and 16.7 mM glucose concentrations. Compared with glibenclamide,
      nuciferine had a stronger effect on insulin secretion and less beta-cell
      toxicity. However, nuciferine did not compete with glibenclamide for binding to
      the sulfonylurea receptor. CONCLUSIONS: Among several compounds extracted from
      anti-diabetic plants, nuciferine was found to stimulate insulin secretion by
      closing potassium-adenosine triphosphate channels, explaining anti-diabetic
      effects of Nelumbo nucifera.

PMID- 22633983
TI  - Evaluation of subchronic toxicity of the hydroethanolic extract of Tropaeolum
      majus in Wistar rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The use of medicinal plants for the treatment of
      diseases usually comes from the belief that they present low toxicity due their
      natural origin. However, it is necessary a toxicological and pharmacological
      evaluation for these plants. Tropaeolum majus is a medicinal plant used in
      popular medicine to treat several diseases, including cardiovascular disorders,
      urinary tract infections and asthma. Even though several studies proved its
      therapeutic effects, there are few toxicological studies with this species. AIM
      OF THE STUDY: The present study was carried out to evaluate the subchronic
      toxicity of the hydroethanolic extract obtained from leaves of T. majus (HETM) in
      Wistar rats. MATERIAL AND METHODS: Male and female Wistar rats received three
      doses of HETM (75, 375 and 750 mg/kg) for 28 days. After the treatments
      biochemical, hematological and histopathological parameters were analyzed.
      RESULTS: No significant alterations in the animal's body weight gain, relative
      organs weight, serum biochemical analysis, hematological or histopathological
      analyses of liver, kidneys and spleen were observed. CONCLUSIONS: These results
      demonstrate the absence of subchronic toxicity due to oral treatment with HETM
      for 28 days in Wistar rats. However, other toxicological studies are necessary to
      evaluate the total safety of this plant.

PMID- 22633984
TI  - GABA, glutamate, dopamine and serotonin transporters expression on forgetting.
AB  - Notwithstanding several neurotransmission systems are frequently related to
      memory formation; forgetting process and neurotransmission systems or their
      transporters; the role of gamma-aminobutyric acid (GAT1), glutamate (EACC1),
      dopamine (DAT) and serotonin (SERT) is poorly understood. Hence, in this paper
      western-blot analysis was used to evaluate expression of GAT1, EAAC1, DAT and
      SERT during forgetting in trained and untrained rats treated with the selective
      serotonin transporter inhibitor fluoxetine, the amnesic drug d-methamphetamine
      (METH) and fluoxetine plus METH. Transporters expression was determined in the
      hippocampus (HIP), prefrontal cortex (PFC) and striatum (STR). Results indicated
      that forgetting of Pavlovian/instrumental autoshaping was associated to up
      regulation of GAT1 (PFC and HIP) and DAT (PFC) while SERT (HIP) was down
      regulated; no-changes were observed in striatum. Methamphetamine administration
      did not affect forgetting at 216 h post-training but up-regulated hippocampal DAT
      and EACC, prefrontal cortex DAT and striatal GAT1 or EACC1. Fluoxetine alone
      prevented forgetting, which was associated to striatal GAT1 and hippocampal DAT
      up-regulation, but prefrontal cortex GAT1 down-regulation. Fluoxetine plus METH
      administration was also able to prevent forgetting, which was associated to
      hippocampal DAT, prefrontal cortex SERT and striatal GAT1, DAT or SERT up
      regulation, but prefrontal cortex GAT1 down-regulation. Together these data show
      that forgetting provokes primarily hippocampal and prefrontal cortex transporters
      changes; forgetting represent a behavioral process hardly modifiable and its
      prevention could causes different transporters expression patterns.

PMID- 22633985
TI  - Novel 7alpha-alkoxy-17alpha-(4'-halophenylethynyl)estradiols as potential
      SPECT/PET imaging agents for estrogen receptor expressing tumours: synthesis and
      binding affinity evaluation.
AB  - In order to develop potential radiolabelled probes for imaging estrogen receptor
      (ER) positive tumours, we have synthesized and characterized a series of novel
      7alpha-alkoxy-17alpha-(4'-iodophenylethynyl)estra-1,3,5(10)-triene-3,17beta-diols
      and 7alpha-alkoxy-17alpha-(4'-fluorophenylethynyl)estra-1,3,5(10)-triene-3,17beta
      diols. The fluoro-substituted compounds showed a higher ER binding affinity than
      the corresponding iodo-derivatives, where 7alpha-methoxy- and 17alpha-(4'
      fluorophenylethynyl)estra-1,3,5(10)-triene-3,17beta-diol showed the highest ER
      binding affinities (RBA=80.9% and 78.9%, respectively), among the
      halophenylethynyl compounds studied and should be further explored as potential
      PET biomarkers for imaging of ER expressing tumours.

PMID- 22633986
TI  - Current management of gastrointestinal stromal tumors--a comprehensive review.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) comprise < 1% of all
      gastrointestinal (GI) tumors, but GISTs are the most common mesenchymal tumors of
      the GI tract. Dramatic changes in clinical practice have been observed in the
      last decade. This review highlights the overall management of GIST and its recent
      developments. METHOD: We identified literature by searching Medline and PubMed
      from January 1995 to December 2011 using the keywords "gastrointestinal stromal
      tumors", "GIST", "imatinib" and "tyrosine kinase inhibitor". Additional papers
      were identified by a manual search of the references from the key articles. There
      were no exclusion criteria for published information to the topics. RESULTS: For
      localized primary GISTs, surgical resection is the mainstay of therapy. The 5
      year survival rate after complete resection of GISTs is approximately 50%-65%.
      Many factors including tumor size, mitotic rate, tumor location, kinase
      mutational status and occurrence of tumor rupture have been extensively studied
      and proposed to be predictors of survival outcomes. Adjuvant imatinib is proposed
      as an option for those patients with a substantial risk of relapse. Unresectable
      metastatic or recurrent GIST can be treated with a tyrosine kinase inhibitor,
      imatinib, with a remarkable response (50%-70%) and prolonged survival (median
      progression-free survival: 18-20 months; median overall survival: 51-57 months).
      The standard approach in the case of tumor progression on 400 mg once per day is
      to increase the imatinib dose to 400 mg twice per day as permitted by toxicity.
      Use of a second-line targeted agent, sunitinib, in patients with advanced GIST
      who fail (or are intolerant of) imatinib therapy is advised. CONCLUSION:
      Treatment for GISTs has become increasingly complex because of the growing
      understanding of its biology. A multidisciplinary team that includes
      radiologists, medical oncologists, pathologists, and surgeons is paramount for
      the effective treatment of GIST.

PMID- 22633987
TI  - Longitudinal measures of serum albumin and prealbumin concentrations in incident
      dialysis patients: the comprehensive dialysis study.
AB  - OBJECTIVE: Serum albumin and prealbumin concentrations are strongly associated
      with the risk of death in dialysis patients. Our study examined the association
      among demographic characteristics, body composition, comorbidities, dialysis
      modality and access, inflammation, and longitudinal measures of albumin and
      prealbumin concentrations in incident dialysis patients. DESIGN, SETTING,
      SUBJECTS, AND OUTCOME MEASURES: The Comprehensive Dialysis Study is a prospective
      cohort study of incident dialysis patients; in this report, we examined the data
      from 266 Nutrition substudy participants who donated serum. The independent
      variables of interest were baseline age, sex, race, Quetelet's (body mass) index,
      dialysis modality and access, diabetes, heart failure, atherosclerotic vascular
      disease, serum creatinine level, and longitudinal measures of C-reactive protein.
      The outcomes of interest (dependent variables) were longitudinal measures of
      albumin and prealbumin concentrations, recorded at study entry and thereafter
      every 3 months for 1 year. RESULTS: In multivariable mixed linear models, female
      sex, peritoneal dialysis, hemodialysis with a catheter, and higher C-reactive
      protein concentrations were associated with lower serum albumin concentrations,
      and serum albumin concentrations increased slightly over the year. In comparison,
      prealbumin concentrations did not significantly change over time; female sex,
      lower body mass index, diabetes, atherosclerotic vascular disease, and higher C
      reactive protein concentrations were associated with lower prealbumin
      concentrations. Serum creatinine had a curvilinear relation with serum albumin
      and prealbumin. CONCLUSIONS: Serum albumin level increases early in the course of
      dialysis, whereas prealbumin level does not, and the predictors of serum
      concentrations differ at any given time. Further understanding of the mechanisms
      underlying differences between albumin and prealbumin kinetics in dialysis
      patients may lead to an improved approach to the management of protein-energy
      wasting.

PMID- 22633988
TI  - Not all phosphate is created equal.

PMID- 22633989
TI  - Peritoneal dialysis patients have higher prevalence of gastrointestinal symptoms
      than hemodialysis patients.
AB  - OBJECTIVE: Malnutrition is common in dialysis patients and is attributed to
      decreased food intake, and/or chronic systemic inflammation linked to dialysis
      related comorbidities and complications. This study aimed to determine the
      prevalence of gastrointestinal (GI) symptoms in dialysis patients and whether
      this impacts food intake. DESIGN: Cross-sectional study. SETTING: Tertiary
      teaching hospital. PARTICIPANTS: All consenting hospital peritoneal dialysis (PD)
      and hemodialysis (HD) patients. METHODS: Patients were interviewed by a dietitian
      regarding the prevalence and impact of GI symptoms (nausea, vomiting, bloating,
      early satiety, diarrhea, heartburn, fatigue, and weight changes). Serum levels of
      albumin were measured, and the use of medication known to cause GI symptoms was
      recorded. MAIN OUTCOME MEASURE: Presence of GI symptoms. RESULTS: The PD (n =
      122) and HD (n = 172) groups were similar in age, gender, and presence of
      diabetes. Serum albumin levels were lower for those on PD compared with HD (3.2
      vs. 3.5 g/dL, P < .001). Eighty-five percent of the patients on PD reported at
      least 1 GI symptom, compared with 51% on HD. Compared with HD, more PD patients
      reported that GI symptoms were related to the onset of dialysis (55% vs. 12%, P <
      .001). A greater number of PD patients (compared with HD patients) reported a
      decrease in food intake (53% vs. 14%, P < .001) and that they had attempted
      dietary changes to alleviate symptoms (34% vs. 9%, P < .001). CONCLUSION: These
      results should influence dietetic educational practice. In addition to the
      provision of adequate protein and energy, dialysis patients should be counselled
      regarding the management of GI symptoms and monitored for the prevalence and
      severity of these symptoms.

PMID- 22633990
TI  - Is urolithiasis in children associated with obesity or malnutrition?
AB  - BACKGROUND: Although it is known that obesity predisposes to urolithiasis, a
      tendency for malnutrition in children with urolithiasis owing to recurrent
      urinary infections and abdominal pain also makes sense. AIMS: In this study, we
      aimed to determine the nutritional status of infants and children with
      urolithiasis, and to observe whether obesity or malnutrition is more prevalent in
      that population. METHODS: One hundred eighty-seven children aged 4 months to 17
      years (mean, 4.9 +/- 4.4 years) with urolithiasis, and 278 age- and sex-matched
      children without any chronic diseases were included. Anthropometric evaluations,
      including weight and height standard deviation score (SDS), body mass index, and
      triceps and subscapular skinfold thickness (SFT), were performed. RESULTS: Mean
      weight SDSs of the patients was statistically lower than that of the control
      subjects (P < .0001). Malnutrition rate was statistically higher in the patients
      with urolithiasis when evaluated according to weight SDS and percentiles of body
      mass index and SFT. When the age factor was taken into account, the percentage of
      malnutrition, determined by the percentiles of triceps and subscapular SFT
      measurements, was found to be higher in children younger than 2 years. Short
      stature was more prevalent in older children. CONCLUSION: Malnutrition among
      children with urolithiasis is not as rare as thought previously. A careful
      anthropometric evaluation should be included in the clinical assessment of those
      children.

PMID- 22633991
TI  - Potential importance of low-sodium bread and breakfast cereal to a reduced sodium
      diet.
AB  - Purchasing data suggest that bread and cereal products are responsible for
      approximately 18% of normal daily unrestricted sodium intake; this percentage may
      be substantially higher in subjects attempting to follow a reduced sodium diet by
      avoiding added salt and salty sauces and meats. Substituting with low-sodium
      bread would be expected to result in a sodium intake reduction of 0.6 g/day or
      higher, depending on the amount of bread normally eaten. Many cold breakfast
      cereals typically contain 0.2 to 0.3 g of sodium per serving. A number of zero
      sodium or low-sodium cold cereal options are commercially available, and many hot
      cereals are available in forms that contain no sodium. Because bread and
      breakfast cereals are not commonly thought of as being salty foods, substituting
      these with low-sodium alternatives might help achieve additional substantial
      sodium intake reduction without much disruption of the diet.

PMID- 22633992
TI  - Serosurvey of antibodies against Toxoplasma gondii and Neospora caninum in white
      tailed deer from Northern Mexico.
AB  - The objective of this study was to determine the seroprevalence of Toxoplasma
      gondii and Neospora caninum in white-tailed deer from Northern Mexico. Sera from
      532 white-tailed deer (Odocoileus virginianus) from three Northern states of
      Mexico were assayed for antibodies to T. gondii by ELISA and western blot. From
      these samples, 368 were available to test for N. caninum antibodies by ELISA. The
      overall prevalence for T. gondii antibodies was 13.9% (74/532; CI(95) 11-17) and
      for N. caninum 8.4% (31/368; CI(95) 6-12). There was a significant association
      between positive ELISA results for T. gondii, with management factors within
      ranches, such number of deer per hectare and geographic location of deer, but
      none for N. caninum. T. gondii infection in the deer from Guerrero, Coahuila had
      an increased risk than those from Nuevo Laredo, Tamaulipas (OR, 8.3; CI(95) 1.9
      35.4; P<0.05) and ranches with one deer in 15 ha had increased risk of positive
      association (OR, 2.61; CI(95) 1.5-4.4; P<0.05). These findings may have
      environmental or public health implications because venison can be an important
      meat source of T. gondii infections for humans and feral cats.

PMID- 22633993
TI  - Post-weaning mice fed exclusively milk have deficits in induction of long-term
      depression in the CA1 hippocampal region and spatial learning and memory.
AB  - Previously, we have found that post-weaning mice fed exclusively milk display low
      frequency exploratory behavior compared to mice fed a food pellet diet (Ishii et
      al., 2005a). Because cognitive functions play a key role in animal exploration,
      in the present study we examined the effect of an exclusively milk formula diet
      on spatial learning and memory in a water maze and also on induction of long-term
      potentiation (LTP) and long-term depression (LTD) at the Schaffer collateral-CA1
      synapse in the hippocampus. Exclusively milk-fed mice exhibited slower learning
      and memory deficits in hidden water maze tests as compared with pellet-fed mice.
      Moreover, milk-fed mice showed a significant inhibition of LTD but a normal
      induction of LTP. Despite these functional deficits, adult neurogenesis in the
      dentate gyrus of the hippocampus, which has been proposed to have a causal
      relationship to spatial memory, was stimulated in milk-fed mice. These result
      suggest that an exclusively milk formula diet after weaning leads to a
      stimulation of hippocampal neurogenesis but causes deficits in the induction of
      LTD in the CA1 hippocampal region and impairment of spatial learning and memory.

PMID- 22633994
TI  - Dectin-1/Syk signaling is involved in Lactobacillus casei cell wall extract
      induced mouse model of Kawasaki disease.
AB  - Kawasaki disease (KD) is not only the leading cause of childhood acquired heart
      diseases, but also causes profound coronary artery sequelae due to chronic
      vascular inflammation in adulthood. Of unknown underlying mechanism, both innate
      and adaptive immune responses are involved in the pathogenesis of coronary artery
      lesions (CALs). We investigated the role of dectin-1/spleen tyrosine kinase (Syk)
      pathway on macrophage in responsive to Lactobacillus casei cell wall extract
      (LCWE) in vitro and in vivo. We found that LCWE induced in vitro macrophage
      activation with increased production of IL-6, TNF-alpha, and MCP-1, concomitantly
      with Syk activation, and dectin-1 and TLR2 enhancement. In vivo, LCWE induced
      infiltration of dectin-1(+) macrophages into CALs and cardiac upregulation of IL
      6 and MCP-1 on day 14 post-injection. Most importantly, Syk inhibition alleviated
      LCWE-induced arteritis in BALB/c mice. Blockade of either dectin-1 or Syk
      significantly inhibited LCWE-induced IL-6 and MCP-1 production both in vitro and
      in vivo. This study demonstrates that the macrophage dectin-1/Syk-mediated
      pathway is involved in LCWE-induced CALs and production of IL-6 and MCP-1. Given
      the functional equivalence of human dectin-1 to murine, the importance of dectin
      1/Syk pathway in the development of murine CALs warrants further investigation on
      their roles in human KD.

PMID- 22633995
TI  - Pneumonia hospitalization in Brazil from 2003 to 2007.
AB  - OBJECTIVES: In emerging countries, pneumonia is a leading cause of
      hospitalization and death, particularly among the youngest and oldest. This
      retrospective study aimed to quantify the incidence of hospitalization due to all
      cause pneumonia (HDTP) and in-hospital case fatality rates (CFRs) in all age
      groups, in five administrative regions of Brazil. METHODS: The International
      Classification of Diseases Tenth Revision coding for pneumonia (J12-J18) and an
      interactive web-based database of individuals covered by the Unified Health
      System in Brazil who were hospitalized from 2003 to 2007, were used to identify
      cases. In-hospital CFRs were the percentage of hospitalized cases that died.
      RESULTS: The overall HDTP incidence per 100,000 people of all ages decreased from
      451 in 2003 to 388 in 2007. When categorized by age group, the HDTP incidence was
      lowest for those aged 5-49 years, and highest in children aged <=4 years and
      adults aged >=50 years. The in-hospital CFR increased from 2.89% in 2003 to 4.02%
      in 2007. Regional differences in HDTP incidence rates and in-hospital CFR were
      observed from 2003 to 2007. CONCLUSIONS: As expected, the highest HDTP rates were
      observed in the very young and the elderly. Regional differences in
      hospitalization incidence rates and in-hospital CFRs were observed.

PMID- 22633996
TI  - Effect of hypoxia on metabolic rate, core body temperature, and c-fos expression
      in the naked mole rat.
AB  - Recent investigations of hypoxia physiology in the naked mole rat have opened up
      an interesting line of research into the basic physiological and genomic
      alterations that accompany hypoxia survival. The extent to which such findings
      connect the effect of hypoxia to metabolic rate (O2 consumption), core body
      temperature (Tb), and transcripts encoding the immediate early gene product (such
      as c-fos) under a constant ambient temperature (Ta) is not well known. We
      investigated this issue in the current study. Our first sets of experiments
      measured Tb and metabolic rates during exposure of naked mole rats to hypoxia
      over a constant Ta. Hypoxia significantly decreased metabolic rates in the naked
      mole rat. Although core Tb also decreased during hypoxia, the effect of hypoxia
      in suppressing core Tb was not significant. The second series of experiments
      revealed that c-fos protein and mRNA expression in the hippocampus neurons (CA1)
      increased in naked mole rats that were repeatedly exposed to 3% O2 for 60 min per
      day for 5 days when compared to normoxia. Our findings provide evidence for the
      up-regulation of c-fos and suppression of metabolic rate in hypoxia tolerating
      naked mole rats under constant ambient temperature. Metabolic suppression and c
      fos upregulation constitute part of the physiological complex associated with
      adaptation to hypoxia.

PMID- 22633997
TI  - Long-term prognosis of patients with ulcerative colitis treated with cytapheresis
      therapy.
AB  - BACKGROUND: Although accumulating studies in Japan show that cytapheresis (CAP)
      therapy is safe and effective for the induction of remission of moderate or
      severe ulcerative colitis (UC), the long-term prognosis of UC patients treated
      with CAP is unknown. The aim of this study was to determine the long-term
      prognosis of UC patients treated with CAP. METHODS: Ninety patients treated
      previously with CAP and followed for more than 3 years were evaluated. The rates
      of operation, readmission, and use or dose-up of corticosteroid were analyzed as
      long-term prognosis. RESULTS: Following the first course of CAP treatment, 64% of
      patients showed clinical improvement (> 4-point decrease in the clinical activity
      index (CAI)), and 49% of patients achieved clinical remission (CAI <= 4). Longer
      disease duration and lower age at the first CAP treatment correlated
      significantly with the therapeutic effects of CAP (p = 0.003 and 0.035,
      respectively). The rates of operation and readmission were significantly lower in
      patients who showed previous clinical effects of CAP than in those who did not
      respond to CAP. The rates of operation and readmission were also significantly
      lower in patients whose treatment was combined with immunomodulators after the
      initiation of CAP than in patients who did not use immunomodulators. Importantly,
      the second course of CAP was also effective in most of the patients who showed a
      clinical response to the first CAP. CONCLUSIONS: Patients who achieve remission
      after the first CAP therapy may have a good long-term prognosis and a good
      response to a second CAP therapy even after relapse.

PMID- 22633999
TI  - Are head bandages required post-pinnaplasty?
AB  - A best evidence topic in ear, nose and throat surgery was written according to a
      structured protocol. The question addressed was: In patients who are undergoing
      pinnaplasty for prominent ears, does the use of post-operative head bandages as
      compared to not using post-operative head bandages improve clinical outcomes? A
      total of 121 papers were identified using the reported search protocol, of which
      five articles 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. All five
      studies showed that no advantage exists in using head bandages with patients who
      have undergone pinnaplasty. Four of the five studies concluded that head bandages
      should not be utilised at all, whereas two of the five studies suggested that
      there is little reason to use head bandages after the first 24 h post
      pinnaplasty. Therefore, the clinical bottom line is that provided the pinnaplasty
      result is good at time of surgery, there is reasonable evidence to suggest that
      head bandages have no effect on complications or patient satisfaction, so at best
      they are unnecessary and at worst, their physical drawbacks may actually outweigh
      any of their perceived benefits.

PMID- 22633998
TI  - Environmental enteropathy: critical implications of a poorly understood
      condition.
AB  - Environmental enteropathy (also called tropical enteropathy) is a subclinical
      condition caused by constant fecal-oral contamination and resulting in blunting
      of intestinal villi and intestinal inflammation. Although these histological
      changes were discovered decades ago, the clinical impact of environmental
      enteropathy is just starting to be recognized. The failure of nutritional
      interventions and oral vaccines in the developing world may be attributed to
      environmental enteropathy, as the intestinal absorptive and immunologic functions
      are significantly deranged. Here we review the existing literature and examine
      potential mechanisms of pathogenesis for this poorly understood condition.

PMID- 22634000
TI  - Selection of reference genes for real-time expression studies in Streptococcus
      agalactiae.
AB  - Streptococcus agalactiae, group B streptococci (GBS) is the leading cause of
      severe bacterial infections in newborns. GBS expression studies allowed the
      identification and characterization of virulence factors and a better
      understanding of the host-pathogen-environment interactions. The measurement of
      transcript levels by quantitative real-time PCR (qRT-PCR) is a widely used
      technique in GBS; however, a systematic evaluation and validation of reference
      gene stability for normalization purposes in GBS expression studies is currently
      lacking. Therefore, we analyzed the stability of 10 candidate reference genes
      (16SrRNA, glcK, glnA, groEL, gyrA, recA, rpoB, rpsL, sdhA and tkt) in three GBS
      prototype strains (O90R, NEM316 and 2603V/R) grown at different temperature
      conditions (37 degrees C and 40 degrees C). Our approach was based on the
      calibration of transcript levels from each gene against the number of bacteria
      from the same sample (ratio messenger RNA/genomic DNA). As a complementary
      analysis, reference gene stability was also investigated through the
      bioinformatic applications, geNorm and NormFinder. Considering the whole GBS
      development cycle, only a minority of genes were stable under both growth
      conditions, but this number increased when restricting the analysis to the
      logarithmic time-points. The range of stable genes was higher at 37 degrees C,
      where recA and sdhA were stable simultaneously for the three strains, and six out
      of 10 genes were stable for at least two strains. At 40 degrees C, recA showed up
      again as one of the best options, suggesting its potential use as reference gene
      in future qRT-PCR studies. The results generated with geNorm and NormFinder were
      consistent with those obtained experimentally and evidenced minor variations
      either among strains or temperature conditions. In conclusion, the fluctuation of
      expression of reference genes observed among different GBS strains and growth
      conditions highlights the importance of carefully validating, for each
      experimental scenario, the use of reference genes for qRT-PCR normalization
      purposes. Nevertheless, recA seems to be a good candidate for such optimizations.

PMID- 22634001
TI  - Rapid detection and antimicrobial resistance gene profiling of Yersinia pestis
      using pyrosequencing technology.
AB  - When a bioterrorism attack is attempted or perpetrated there is considerable risk
      for public health and large scale socioeconomic consequences. It is imperative
      that we possess established assays for the rapid identification of biothreat
      agents with high sensitivity and specificity to ensure emergency response
      measures can be deployed appropriately. Highly trustworthy information within a
      relevant timeframe is required to make a rapid and informed decision. Obtaining
      DNA sequence data from a suspected agent provides an added layer of confidence
      compared to a presumptive positive PCR amplicon. Sequencing based technologies,
      such as pyrosequencing, have sufficient discrimination potential to be used for
      microbial identification and can also be used to identify antimicrobial
      resistance (AMR) genes. We have shown in this study the power of pyrosequencing
      in the unambiguous detection and identification of nine Yersinia pestis strains
      based on virulence genes. Furthermore, we developed assays to characterize their
      AMR gene profiles. Sequence results ranging from 40 to 84bp were generated in
      about 60 min following initial PCR amplification and provide a rapid method for
      determining the AMR profile as compared to the conventional plate method which
      takes several days. The high sequence identities (95-100%) and specificity
      observed indicate the high level of accuracy of pyrosequencing technology. In
      addition, the read lengths of up to 84 bp observed in this study are
      unprecedented for pyrosequencing using the Pyromark Q24. We propose this method
      as a novel, rapid, sequence based detection and identification tool for Y. pestis
      with a potential application in biodefence.

PMID- 22634002
TI  - The role of myofibroblasts in upregulation of S100A8 and S100A9 and the
      differentiation of myeloid cells in the colorectal cancer microenvironment.
AB  - BACKGROUND/AIM: S100A8/A9 and myeloid cells in the tumor microenvironment play an
      important role in cancer invasion and progression, and the effect of tumor
      infiltrated myofibroblasts on myeloid cells in the tumor microenvironment is
      relatively unknown. Accordingly, we investigated the role of myofibroblasts in
      the upregulation of S100A8/A9 as well as in the differentiation of myeloid cells
      in the colorectal cancer (CRC) microenvironment. MATERIALS AND METHODS: To
      investigate the interactions among cancer cells, myofibroblasts, and inflammatory
      cells in the microenvironment of CRC, we used 10 CRC cell lines, 18CO cells and
      THP-1 cells, which were co-cultured with each other or cultured in conditioned
      media (CM) of other cells. Expression of S100A8/A9 was evaluated via Western
      blot, immunohistochemical staining and immunofluorescence. The secreted factors
      from the cell lines were analyzed using cytokine antibody array. Flow cytometry
      analysis was performed to analyze the differentiation markers of myeloid cells.
      RESULTS: 18CO CM induced increased expression of S100A8/A9 in THP-1 cells.
      Increased expression of S100A8/A9 was noted in inflammatory cells of the peri-
      and intra-tumoral areas, along with myofibroblasts in colon cancer tissue.
      S100A8/A9-expressing inflammatory cells also exhibited CD68 expression in colon
      cancer tissue, and 18CO CM induced differentiation of THP-1 cells into myeloid
      derived suppressor cells (MDSCs) or M2 macrophages expressing S100A8/A9.
      Significant amounts of IL-6 and IL-8 were detected in 18CO CM, compared to those
      in both controls and THP-1 CM, and tumor-infiltrated myofibroblasts expressed IL
      8 in colon cancer tissue. Finally, neutralizing antibodies to IL-6 and IL-8
      attenuated 18CO CM-induced increased expression of S100A8/A9. CONCLUSIONS: The
      upregulation of S100A8/A9 in tumor-infiltrated myeloid cells could be triggered
      by IL-6 and IL-8 released from myofibroblasts, and myofibroblasts might induce
      the differentiation of myeloid cells into S100A8/9-expressing MDSCs or M2
      macrophages in the CRC microenvironment.

PMID- 22634003
TI  - cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in
      rat hepatocytes.
AB  - Tumor necrosis factor alpha (TNF) is a pleiotropic proinflammatory cytokine that
      plays a role in immunity and the control of cell proliferation, cell
      differentiation, and apoptosis. The pleiotropic nature of TNF is due to the
      formation of different signaling complexes upon the binding of TNF to its
      receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian
      cells when the cells are co-treated with a transcription inhibitor like
      actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein,
      TNF receptor-associated protein with death domain (TRADD), through its
      cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling
      proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor
      associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex
      combines with FADD and procaspase-8, converts into a death-inducing signaling
      complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that
      regulates various cellular processes such as cell proliferation, gene expression,
      and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in
      various cell types, including hepatocytes. We found that a cAMP analogue,
      dibutyryl cAMP (db-cAMP), inhibits TNF+ActD-induced apoptosis in rat hepatocytes.
      The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of
      cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various
      apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and
      caspase-3 cleavage. We also found that cAMP exerts its affect at the proximal
      level of TNF signaling by inhibiting the formation of the DISC complex upon the
      binding of TNF to TNFR1. In conclusion, our study shows that cAMP prevents
      TNF+ActD-induced apoptosis in rat hepatocytes by inhibiting DISC complex
      formation.

PMID- 22634004
TI  - Evaluation of substrate and inhibitor binding to yeast and human
      isoprenylcysteine carboxyl methyltransferases (Icmts) using biotinylated
      benzophenone-containing photoaffinity probes.
AB  - Isoprenylcysteine carboxyl methyltransferases (Icmts) are a class of integral
      membrane protein methyltransferases localized to the endoplasmic reticulum (ER)
      membrane in eukaryotes. The Icmts from human (hIcmt) and Saccharomyces cerevisiae
      (Ste14p) catalyze the alpha-carboxyl methyl esterification step in the post
      translational processing of CaaX proteins, including the yeast a-factor mating
      pheromones and both human and yeast Ras proteins. Herein, we evaluated synthetic
      analogs of two well-characterized Icmt substrates, N-acetyl-S-farnesyl-L-cysteine
      (AFC) and the yeast a-factor peptide mating pheromone, that contain photoactive
      benzophenone moieties in either the lipid or peptide portion of the molecule. The
      AFC based-compounds were substrates for both hIcmt and Ste14p, whereas the a
      factor analogs were only substrates for Ste14p. However, the a-factor analogs
      were found to be micromolar inhibitors of hIcmt. Together, these data suggest
      that the Icmt substrate binding site is dependent upon features in both the
      isoprenyl moiety and upstream amino acid composition. Furthermore, these data
      suggest that hIcmt and Ste14p have overlapping, yet distinct, substrate
      specificities. Photocrosslinking and neutravidin-agarose capture experiments with
      these analogs revealed that both hIcmt and Ste14p were specifically photolabeled
      to varying degrees with all of the compounds tested. Our data suggest that these
      analogs will be useful for the future identification of the Icmt substrate
      binding sites.

PMID- 22634005
TI  - Arterial shear stress augments the differentiation of endothelial progenitor
      cells adhered to VEGF-bound surfaces.
AB  - Our ongoing studies show that vascular endothelial cell growth factor (VEGF)
      bound surfaces selectively capture endothelial progenitor cells (EPCs) in vitro
      and in vivo, and that surface-bound VEGF stimulates intracellular signal
      transduction pathways over prolonged culture periods, resulting in inductive
      differentiation of EPCs. In this article, we investigated whether simulated
      arterial shear stress augments the differentiation of EPCs adhered to a VEGF
      bound surface. Human peripheral blood-derived mononuclear cells adhered to a VEGF
      bound surface were exposed to 1 day of shear stress (15 dynes/cm(2),
      corresponding to shear load in arteries). Shear stress suppressed the expression
      of mRNAs encoding CD34 and CD133, which are markers for EPCs, and augmented the
      expression of mRNAs encoding CD31 and von Willebrand factor (vWF) as well as vWF
      protein, which are markers for endothelial cells (ECs). Shear stress enhanced
      expression of ephrinB2 mRNA, a marker for arterial ECs, but did not significantly
      change expression of EphB4 mRNA, a marker for venous ECs. Focused protein array
      analysis showed that mechanotransduction by shear stress activated the p38 and
      MAPK pathways in EPCs. Thus, arterial shear stress, in concert with surface-bound
      VEGF, augments the differentiation of EPCs. These results strongly support
      previous observation of rapid differentiation of EPCs captured on VEGF-bound
      stents in a porcine model.

PMID- 22634006
TI  - TRIM45 negatively regulates NF-kappaB-mediated transcription and suppresses cell
      proliferation.
AB  - The NF-kappaB signaling pathway plays an important role in cell survival,
      immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF
      kappaB is regulated by several posttranslational modifications including
      phosphorylation, neddylation and ubiquitination. The NF-kappaB signaling pathway
      is activated by two distinct signaling mechanisms and is strictly modulated by
      the ubiquitin-proteasome system. It has been reported that overexpression of
      TRIM45, one of the TRIM family ubiquitin ligases, suppresses transcriptional
      activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In
      this study, we showed that TRIM45 also negatively regulates TNFalpha-induced NF
      kappaB-mediated transcription by a luciferase reporter assay and that TRIM45
      lacking a RING domain also has an activity to inhibit the NF-kappaB signal.
      Moreover, we found that TRIM45 overexpression suppresses cell growth. These
      findings suggest that TRIM45 acts as a repressor for the NF-kappaB signal and
      regulates cell growth.

PMID- 22634007
TI  - Inhibition of Lp(a)-induced functional impairment of endothelial cells and
      endothelial progenitor cells by hepatocyte growth factor.
AB  - BACKGROUND: Lipoprotein (a) (Lp(a)) is one of the risk factors for peripheral
      artery disease (PAD). Our previous report demonstrated that hepatocyte growth
      factor (HGF) gene therapy attenuated the impairment of collateral formation in
      Lp(a) transgenic mice. Since risk factors for atherosclerosis accelerate
      endothelial senescence and impair angiogenesis, we examined the role of Lp(a) in
      dysfunction and senescence of endothelial progenitor cells (EPC) and endothelial
      cells. METHODS: In vitro and in vivo incorporation assays were performed using ex
      vivo expanded DiI-labeled human EPC. Senescence of cultured endothelial cells,
      production of oxidative stress and angiogenesis function were evaluated by SA
      beta-galactosidase staining, dihydroethidium (DHE) staining and Matrigel assay,
      respectively. RESULTS: EPC transplantation significantly stimulated recovery of
      ischemic limb perfusion, while EPC pre-treated with Lp(a) did not increase
      ischemic limb perfusion. Impairment of angiogenesis by EPC with Lp(a) was
      associated with a significant decrease in CD31-positive capillaries and DiI
      labeled EPC. Importantly, Lp(a) significantly accelerated the onset of senescence
      and production of reactive oxygen species (ROS) in human aortic endothelial
      cells, accompanied by a significant increase in the protein expression of p53 and
      p21. On the other hand, HGF significantly attenuated EPC dysfunction, senescence,
      ROS production, and p53 and p21 expression induced by Lp(a). CONCLUSION: Lp(a)
      might affect atherosclerosis via acceleration of senescence, ROS production, and
      functional impairment of the endothelial cell lineage. HGF might have inhibitory
      effects on these atherogenic actions of Lp(a).

PMID- 22634008
TI  - Combined anti-tumor effects of IFN-alpha and sorafenib on hepatocellular
      carcinoma in vitro and in vivo.
AB  - Hepatocellular carcinoma (HCC) is among the most common and aggressive cancers
      worldwide, and novel therapeutic strategies are urgently required to improve
      clinical outcome. Interferon-alpha (IFN-alpha) and sorafenib are widely used as
      anti-tumor agents against various malignancies. In this study, we investigated
      the combined effects of IFN-alpha and sorafenib against HCC. We demonstrated that
      the combination therapy synergistically suppressed HCC cellular viability,
      arrested cell cycle propagation and induced apoptosis in HCC cells. Further
      research revealed that IFN-alpha and sorafenib collaboratively regulated the
      expression levels of cell cycle-related proteins Cyclin A and Cyclin B as well as
      the pro-survival Bcl-2 family proteins Mcl-1, Bcl-2 and Bcl-X(L). Moreover,
      sorafenib inhibited IFN-alpha induced oncogenic signaling of STAT3, AKT and ERK
      but not the activation of the tumor suppressor STAT1. Xenograft experiments also
      confirmed the combined effects of IFN-alpha and sorafenib on tumor growth
      inhibition and apoptosis induction in vivo. In conclusion, these results provide
      rationale for the clinical application of IFN-alpha and sorafenib combination
      therapy in HCC treatment.

PMID- 22634009
TI  - Insulin/insulin-like growth factor (IGF) stimulation abrogates an association
      between a deubiquitinating enzyme USP7 and insulin receptor substrates (IRSs)
      followed by proteasomal degradation of IRSs.
AB  - Insulin receptor substrates (IRSs) play central roles in insulin/insulin-like
      growth factor (IGF) signaling and mediate a variety of their bioactivities. IRSs
      are tyrosine-phosphorylated by activated insulin receptor/IGF-I receptor tyrosine
      kinase in response to insulin/IGF, and are recognized by signaling molecules
      possessing the SH2 domain such as phosphatidylinositol 3-kinase (PI3K), leading
      to the activation of downstream pathways. Recent studies have suggested that
      degradation of IRSs by the ubiquitin-proteasome pathway leads to impaired
      insulin/IGF signaling, but the precise mechanism underlying the process is still
      unclear. In this study, we identified deubiquitinating enzyme ubiquitin specific
      protease 7 (USP7) as an IRS-2-interacting protein and demonstrated that
      deubiquitinase activity of USP7 plays important roles in IRS-2 stabilization
      through the ubiquitin-proteasome pathway. In addition, insulin treatment
      dissociated USP7 from IRS-2, leading to degradation of IRS-2. This dissociation
      was prevented by treatment with LY294002, a PI3K inhibitor, indicating that
      insulin activation of the PI3K pathway leads to dissociation of IRS-2 from USP7
      and IRS-2 degradation. We obtained similar results for IRS-1 in cells treated
      with insulin and for IRS-2 in cells treated with IGF-I. Taken together, this is
      the first report demonstrating that USP7 is an IRS-1/2 deubiquitinating enzyme
      forming a negative feedback loop in insulin/IGF signaling.

PMID- 22634011
TI  - Staurosporine induces ganglion cell differentiation in part by stimulating
      urokinase-type plasminogen activator expression and activation in the developing
      chick retina.
AB  - Here, we investigated whether staurosporine-mediated urokinase-type plasminogen
      activator (uPA) activation is involved in retinal ganglion cell (RGC)
      differentiation. Retinal cells were isolated from developing chick retinas at
      embryonic day 6 (E6). Relatively few control cells grown in serum-free medium
      started to form processes by 12 h. In contrast, staurosporine-treated cells had
      processes within 3h, and processes were evident at 8 h. Immunofluorescence
      staining showed that Tuj-1-positive cells with shorter neurites could be detected
      in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with
      longer neuritic extensions were seen in staurosporine-treated cultures. BrdU
      positive proliferating cells were more numerous in control cultures than in
      staurosporine-treated cultures, and the BrdU staining was not detected in post
      mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed
      that staurosporine induced high levels of the active form of uPA. The
      staurosporine-induced uPA signal was localized predominantly in the soma,
      neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of
      uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length,
      neurite number, and uPA staining versus controls. In developing retinas in ovo,
      amiloride administration remarkably reduced the staurosporine-induced uPA
      staining and RGC differentiation. Taken together, our in vitro and in vivo data
      collectively indicate that uPA plays a role in the staurosporine-mediated
      stimulation of RGC differentiation.

PMID- 22634012
TI  - The inhibitory effect of BIM (I) on L-type Ca2+ channels in rat ventricular
      cells.
AB  - We investigated the effect of a specific protein kinase C (PKC) inhibitor,
      bisindolylmaleimide I [BIM (I)], on L-type Ca(2+) channels in rat ventricular
      myocytes. BIM (I) alone inhibited the L-type Ca(2+) current in a concentration
      dependent manner, with a K(d) value of 3.31 +/- 0.25 MUM, and a Hill coefficient
      of 2.34 +/- 0.23. Inhibition was immediate after applying BIM (I) in the bath
      solution and then it partially washed out. The steady-state activation curve was
      not altered by applying 3MU M BIM (I), but the steady-state inactivation curve
      shifted to a more negative potential with a change in the slope factor. Other PKC
      inhibitors, PKC-IP and chelerythrine, showed no significant effects either on the
      L-type Ca(2+) current or on the inhibitory effect of BIM (I) on the L-type Ca(2+)
      current. The results suggest that the inhibitory effect of BIM (I) on the L-type
      Ca(2+) current is independent of the PKC pathway. Thus, our results should be
      considered in studies using BIM (I) to inhibit PKC activity and ion channel
      modulation.

PMID- 22634010
TI  - Acetaminophen inhibits cytochrome c redox cycling induced lipid peroxidation.
AB  - Cytochrome (cyt) c can uncouple from the respiratory chain following
      mitochondrial stress and catalyze lipid peroxidation. Accumulating evidence shows
      that this phenomenon impairs mitochondrial respiratory function and also
      initiates the apoptotic cascade. Therefore, under certain conditions a
      pharmacological approach that can inhibit cyt c catalyzed lipid peroxidation may
      be beneficial. We recently showed that acetaminophen (ApAP) at normal
      pharmacologic concentrations can prevent hemoprotein-catalyzed lipid peroxidation
      in vitro and in vivo by reducing ferryl heme to its ferric state. We report here,
      for the first time, that ApAP inhibits cytochrome c-catalyzed oxidation of
      unsaturated free fatty acids and also the mitochondrial phospholipid,
      cardiolipin. Using isolated mitochondria, we also showed that ApAP inhibits
      cardiolipin oxidation induced by the pro-apoptotic protein, tBid. We found that
      the IC(50) of the inhibition of cardiolipin oxidation by ApAP is similar in both
      intact isolated mitochondria and cardiolipin liposomes, suggesting that ApAP
      penetrates well into the mitochondria. Together with our previous results, the
      findings presented herein suggest that ApAP is a pleiotropic inhibitor of
      peroxidase catalyzed lipid peroxidation. Our study also provides a potentially
      novel pharmacological approach for inhibiting the cascade of events that can
      result from redox cycling of cyt c.

PMID- 22634013
TI  - Spontaneous curvature of ganglioside GM1--effect of cross-linking.
AB  - The membrane-curvature dependent lateral distribution of outer leaflet
      ganglioside GM1 (GM1) and the influence of GM1 cross-linking induced by
      fluorophore-tagged cholera toxin subunit B (CTB) plus anti-CTB was analysed in
      cell membranes by fluorescence microscopy. Data are presented indicating that
      cross-linked GM1-ligand patches accumulated at the tips of human erythrocyte
      echinocytic spiculae induced by Ca(2+)/ionophore A23187. However, when lipid
      fixative osmium tetroxide was added prior to the ligand no accumulation in
      spiculae occurred. GM1-staining remained here distributed over the spheroid cell
      body and in spiculae. Similarly, osmium tetroxide completely prohibited CTB plus
      anti-CTB-induced GM1 patching in representatives for flat membrane, i.e. discoid
      erythrocytes and K562 cells. Our results demonstrate that GM1 per se shows low
      membrane curvature dependent distribution and therefore holds flexible
      spontaneous curvature. In contrast, the cross-linked GM1-ligand complex has a
      strong preference for highly outward curved membrane and possesses overall
      positive spontaneous curvature. Osmium tetroxide efficiently immobilises GM1.

PMID- 22634014
TI  - Elevated amyloid beta production in senescent retinal pigment epithelium, a
      possible mechanism of subretinal deposition of amyloid beta in age-related
      macular degeneration.
AB  - Age-related macular degeneration (AMD) is the most common cause of legal
      blindness in the elderly individuals in developed countries. Subretinally
      deposited amyloid beta (Abeta) is a main contributor of developing AMD. However,
      the mechanism causing Abeta deposition in AMD eyes is unknown. Aging is the most
      significant risk of AMD, thus, we examined the effect of aging on subretinal
      Abeta deposition. mRNAs and cell lysates were isolated from retinal pigment
      epithelial (RPE) cells derived from 24-month-old (24M RPE) and 2-month-old (2M
      RPE) C57BL/6 mice. Abeta concentration in culture supernatants was measured by
      ELISA. Activity and expression of proteins that regulate Abeta level were
      examined by activity assay and real time PCR. Effect of beta-secretase (BACE) on
      Abeta production was examined by siRNA silencing. Abeta amounts in supernatants
      of 24M RPE were significantly higher than 2M RPE. Activity and mRNA levels of
      neprilysin, an Abeta degrading enzyme, were significantly decreased in 24M RPE
      compared to 2M RPE. PCR analysis found that BACE2 was significantly more
      abundantly expressed than BACE1 in RPE cells, however, inactivation of BACE2 gene
      did not affect Abeta production. BACE1 protein amounts did not differ between 24M
      and 2M RPE, however, BACE1 activity was significantly higher in 24M RPE compared
      to 2M RPE. There were no significant changes in the activities of alpha- or gamma
      secretase between 2M and 24M RPE. In conclusion, RPE cells produce more amounts
      of Abeta when they are senescent, and this is probably caused by a decrease in
      Abeta degradation due to a reduction in the expression and activity of neprilysin
      and an increase in Abeta synthesis due to increased activity of BACE1.

PMID- 22634015
TI  - Development and characterization of a human antibody reference panel against
      erythropoietin suitable for the standardization of ESA immunogenicity testing.
AB  - Recombinant human erythropoietin (EPO) has been used therapeutically for more
      than two decades in the treatment of anemia. Although EPO is generally well
      tolerated, in rare cases, patients have developed anti-EPO antibodies that can
      negatively impact safety and efficacy. Therefore, the detection of antibodies
      against EPO is a regulatory requirement during clinical development and post
      approval. Although it is a rare phenomenon, antibody-mediated pure red cell
      aplasia (PRCA) is a serious complication than can result from antibodies that
      develop and neutralize EPO as well as endogenous erythropoietin. Currently, there
      are no universally accepted analytical methods to detect the full repertoire of
      binding and neutralizing anti-EPO antibodies. A number of different methods that
      differ in terms of antibodies detected and assay sensitivities are used by
      different manufacturers. There is also a lack of antibody reference reagents, and
      therefore no consistent basis for detecting and measuring anti-EPO antibodies.
      Reference reagents, with established ranges, are essential to monitor the safety
      and efficacy of all erythropoiesis-stimulating agents (ESAs) structurally related
      to human erythropoietin. This is the first report of the development and
      characterization of a panel of fully human antibodies against EPO suitable as
      reference reagents. The characteristics of antibodies within the panel were
      selected based on the prevalence of non-neutralizing IgG and IgM antibodies in
      non-PRCA patients and neutralizing IgG antibodies, including IgG1 and IgG4, in
      antibody-mediated PRCA subjects. The reference panel includes antibodies of high-
      and low-affinity with binding specificity to neutralizing and non-neutralizing
      erythropoietin epitopes. The subclass of human antibodies in this reference panel
      includes an IgG1, IgG2, and IgG4, as well as an IgM isotype. This antibody panel
      could help select appropriate immunogenicity assays, guide validation, and
      monitor assay performance. Further, this human anti-ESA antibody panel may help
      set the limits of each assay platform in terms of the full repertoire of the anti
      ESA antibodies, and may facilitate standardization of ESA immunogenicity
      reporting across assay platforms.

PMID- 22634016
TI  - New triterpenoids from the stems and leaves of Panax ginseng.
AB  - Three new dammarane-type triterpene saponins ginsenosides Rh(18) (1), Rh(19) (3)
      and Rh(20) (4), along with two new triterpene sapogenins 12beta,23(R)
      epoxydammara-24-ene-3beta,6alpha,20(S)-triol (2) and dammara-(20E)22,25-diene
      3beta,6alpha,12beta,24S-tetrol (5) were isolated from the stems and leaves of
      Panax ginseng C. A. Mey. Their structures were elucidated on the basis of
      spectral evidence and comparisons with literature data.

PMID- 22634017
TI  - Analysis of bacterial polyhydroxybutyrate production by multimodal nanoimaging.
AB  - In this paper, we will employ two microscopy techniques, transmission electron
      microscopy and infrared nanospectromicroscopy, to study the production of
      polyhydroxybutyrate in Rhodobacter capsulatus and to evaluate the influence of
      glucose and acetone on the production yield. The results overlap which leads us
      to a consistent conclusion, highlighting that each technique brings specific and
      complementary information. By using electron microscopy and infrared
      nanospectromicroscopy we have proved that both glucose and acetone had a positive
      effect on the biopolymer production, although the first study done by Fourier
      transform infrared spectroscopy only identified the effect of acetone. In
      conclusion, we have now established a method to be able to perform fast
      diagnostic for PHB production.

PMID- 22634018
TI  - Extramedullary relapse of acute myeloid leukemia after allogeneic hematopoietic
      stem cell transplantation: an easily overlooked but significant pattern of
      relapse.
AB  - Acute myeloid leukemia may manifest as myeloid sarcoma in a variety of
      extramedullary (EM) tissues at diagnosis or at relapse. Although EM relapse after
      allogeneic hematopoietic stem cell transplantation (alloSCT) has been considered
      to be rare, recent studies have suggested that it occurs in 5% to 12% of patients
      who receive alloSCT, accounting for 7% to 46% of total relapses. The incidence of
      EM relapse after immunomodulation (eg, donor lymphocyte infusion) or a second SCT
      is even higher. Moreover, patients with EM relapse are more likely to have had
      preceding acute graft-versus-host disease or chronic graft-versus-host disease
      relative to those with bone marrow relapse. Collectively, these observations
      suggest that the preferential occurrence of the graft-versus-leukemia effect
      underlies the pathogenesis of EM relapse. Establishing an early diagnosis of EM
      relapse has been challenging because of the immense diversity in the relapse
      sites; however, recent studies have suggested the usefulness of (18)F
      fluorodeoxyglucose positron emission tomography scans in the detection of EM
      relapse. As a treatment for EM relapse, a combination of local and systemic
      therapy should be considered, because local therapy alone often results in
      subsequent systemic relapse. The prognosis for patients who develop EM relapse
      after SCT remains poor but is slightly better than that after bone marrow
      relapse. In addition to an early diagnosis with new modalities, clinical studies
      using new agents that may offer systemic activity while preserving the graft
      versus-leukemia effect are warranted as part of an effort to improve the clinical
      outcome.

PMID- 22634019
TI  - Vaginal morcellation: a new strategy for large gynecological malignant tumor
      extraction: a pilot study.
AB  - OBJECTIVE: Evaluate feasibility and safety of a novel technique for uterine
      morcellation in patients scheduled for laparoscopic treatment of gynecologic
      malignances. BACKGROUND: The laparoscopic management of uterine malignancies is
      progressively gaining importance and popularity over laparotomy. Nevertheless,
      minimal invasive surgery is of limited use when patients have enlarged uterus or
      narrow vagina. In these cases, conventional uterus morcellation could be a
      solution but should not be recommended due to risks of tumor dissemination.
      METHODS: Prospective pilot study of women with endometrial cancer in which uterus
      removal was a realistic concern due to both organ size and proportionality. Brief
      technique description: after completion of total laparoscopic hysterectomy and
      bilateral anexectomy, a nylon with polyurethane Lapsac(r) is vaginally inserted
      into the abdomen; the specimen is placed inside the pouch that will be closed and
      rotated 180 degrees  toward the vaginal vault and, posteriorly, pushed into the
      vaginal canal; in the transvaginal phase, the surgeon pulls the edges of the bag
      up to vaginal introitus and all vaginal walls will be covered; inside the pouch,
      the operator performs a uterus bisection-morcellation. RESULTS: In our series of
      8 cases, we achieved successful completion in all patients, without conversion to
      laparotomy. Average operative time, blood loss and length of hospitalization were
      favorable. One patient presented with a vesicovaginal fistula. CONCLUSION: The
      vaginal morcellation following oncologic principles is a feasible method that
      permits a rapid uterine extraction and may avoid a number of unnecessary
      laparotomies. Further studies are needed to confirm the oncological safety of the
      technique.

PMID- 22634020
TI  - "We don't think you're special": is equitable HIV prevention for sexual
      minorities possible?

PMID- 22634021
TI  - Can governments do it better? Merger mania and hospital outcomes in the English
      NHS.
AB  - The literature on mergers between private hospitals suggests that such mergers
      often produce little benefit. Despite this, the UK government has pursued an
      active policy of hospital mergers, arguing that such consolidations will bring
      improvements for patients. We examine whether this promise is met. We exploit the
      fact that between 1997 and 2006 in England around half the short term general
      hospitals were involved in a merger, but that politics means that selection for a
      merger may be random with respect to future performance. We examine the impact of
      mergers on a large set of outcomes including financial performance, productivity,
      waiting times and clinical quality and find little evidence that mergers achieved
      gains other than a reduction in activity. Given that mergers reduce the scope for
      competition between hospitals the findings suggest that further merger activity
      may not be the appropriate way of dealing with poorly performing hospitals.

PMID- 22634022
TI  - Novel approach for productivity enhancement of polyhydroxyalkanoates (PHA)
      production by Cupriavidus necator DSM 545.
AB  - In the global context of increased concerns for our environment, the use of
      bioplastics as a replacement for existing petroleum-based polymers is an
      important challenge. Indeed, bioplastics hardly meet economical and technical
      constraints. One, of the most promising among currently studied bioplastics, is
      the polyhydroxyalkanoate (PHA). To circumvent the economical issue for this
      particular biopolymer one solution can be the enhancement of the overall
      productivity by the improvement of the nutritional medium of the microorganism
      producing the biopolymer. Thus, several nutrition media, supplemented or not with
      sodium glutamate, were tested for the growth and the PHA production by
      Cupriavidus necator DSM 545 strain. The most efficient for the biomass and the
      PHA production improvement were found to be the Luria broth (LB) and the
      Bonnarme's media, both supplemented with 10 g/L sodium glutamate. Hence the
      overall productivity was 33 times enhanced comparing to traditional cultivation
      methods. These results open a new route for the PHA production by C. necator
      which appears to be more suitable on a rich, or enriched, medium with no limiting
      factors.

PMID- 22634023
TI  - Molecular tools for companion diagnostics.
AB  - The heterogeneous nature of cancer results in highly variable therapeutic
      responses even among patients with identical stages and grades of a malignancy.
      The move towards personalised medicine in cancer therapy has therefore been
      motivated by a need to customise therapy according to molecular features of
      individual tumours. Companion diagnostics serves to support early drug
      development, it can provide surrogate markers in clinical trials, and also guide
      selection of individual therapies and monitoring of responses in routine clinical
      care. The era of companion diagnostics can be said to have begun with the
      introduction of the HercepTest - a first-of-a-kind diagnostic tool developed by
      DakoCytomation in 1998 to select patients for therapy with the anticancer drug
      Herceptin (trastuzumab). Herceptin and the paired test proved that companion
      diagnostics can help guide patient-tailored therapies. We will discuss herein
      technologies to analyse companion diagnostics markers at the level of DNA, RNA or
      protein, focusing on a series of methods developed in our laboratory that can
      facilitate drug development and help stratify patients for therapy.

PMID- 22634024
TI  - [Aphakia correction with rigid contact lenses in congenital cataract].
AB  - PURPOSE: To describe follow-up and evaluate functional results of rigid gas
      permeable contact lens wear for the correction of aphakia in infants after
      surgery for congenital cataract. PATIENTS AND METHODS: This retrospective study
      was performed on 23 eyes of 17 children (12 boys and five girls), between three
      days and 36 months of age (median 3.5 months), undergoing cataract extraction
      without primary intraocular lens implantation and fitted only with Menicon((r)) Z
      material contact lenses. Initial fitting visits included history and family
      education. Subsequent examinations were performed at eight days, 15 days, 1
      month, 6 months and 1 year. The four main parameters studied were fit
      characteristics, ease of manipulation, ocular integrity and lens integrity.
      Concurrently, functional results (visual acuity, oculomotor balance) and various
      prognostic factors (associated pathology, age at time of surgery, cataract
      density, unilaterality versus bilaterality, postoperative complications) were
      evaluated. Rigorous systematic amblyopia rehabilitation was performed. RESULTS:
      At the one-month exam, 60% of parents demonstrated proficiency with manipulating
      the lens. On one-year follow-up, three cases of failure were attributable to
      difficulties with lens manipulation. At one year, one infectious complication was
      detected. The lens material demonstrated good resistance to breakage (9% at one
      month) and only a mild tendency toward deposits (few or no deposits in 95% of
      cases at 1 month). With regard to visual outcome, among the children old enough
      to cooperate, visual acuity was better than 3/10 for nine out of 12 eyes, of
      which five eyes were 10/10. With regard to alignment, we noted 12 cases (70.6%)
      of strabismus postoperatively (ten esotropia, two exotropia). The factors
      predictive of good visual acuity correlated with those described in the
      literature: partial cataract, bilateral cataract, and absence of postoperative
      oculomotor disturbance. CONCLUSION: The characteristics of rigid gas-permeable
      contact lenses provide safety and efficacy in aphakic infant eyes. They represent
      an attractive alternative to primary intraocular lens implantation in congenital
      cataract.

PMID- 22634025
TI  - [High intraocular pressure and open angle glaucoma].
AB  - PURPOSE: To study the correlation between high intraocular pressure and the
      primitive glaucoma with opened angle among beninese patients. METHOD: Our study
      was accomplished in the ophtalmological department of the university national
      hospital center of Cotonou. It was retrospective with descriptive and analytical
      aim and extended over a period of 3 years going from January 1st, 2007 till
      December 31st, 2009. It took into account all the patients' files having
      presented high intraocular pressure and to whom the search for primitive glaucoma
      with opened angle was carried out. RESULTS: Among 9406 patients received in
      consultation during the period of study, 129 (corresponding with 258 eyes)
      presented high intraocular pressure that is 1.37%. The age of the patients was
      included between 11 years and 82 years, with a medium age of 54.48 years +/-13.94
      years. Male subjects prevailed (57%), with a sex ratio of 1.3. All the patients
      (100%) consulted for visual decline by far, by near or both at the same time. A
      significant number of eyes (80 eyes - 31%) had a vision by far lower or equal
      with 3/10. The values of ocular pressure were included between 22 mmHg and 62
      mmHg, with an average of 28.13 mmHg +/-6.06 mmHg. The ratios cup/disc varied from
      0.3 to 1 with a medium cup/disc of 0.46+/-0.34. The examination of the field of
      vision with the automatic perimeter showed deteriorations of glaucoma type in 170
      eyes (65.89%). High ocular pressure, optic disc glaucoma excavation and visual
      field defects were associated in 58.13% of the cases with a coefficient of
      correlation (r) higher than 0.87. DISCUSSION: Although the high intraocular
      pressure does not allow to confirm the diagnosis of primitive glaucoma with
      opened angle, it constitutes an essential risk factor. CONCLUSION: We showed in
      this study that in 58.13% of the cases, there is a correlation between the high
      intraocular pressure and the primitive glaucoma with opened angle. Efforts must
      be made to sensitize our populations on the existence of this serious affection
      that is primitive glaucoma with opened angle and on its early tracking which
      begins with the measure of the eye pressure.

PMID- 22634026
TI  - [Eye movement recordings in children with attention deficit hyperactivity
      disorder].
AB  - INTRODUCTION: Attention-Deficit and Hyperactivity Disorder (ADHD) affects 3 to 5%
      of school-aged children. Diagnosis is based on criteria defined by the Diagnostic
      and Statistical Manual of Mental Disorders fourth edition (DSM-IV), and there is
      no specific marker for the disease. Eye movements may be altered in ADHD. The
      goal of this study was to identify difficulties in oculomotor tasks in children
      with ADHD. PATIENTS AND METHODS: Subjects were children with untreated ADHD (n=7)
      and age- and gender-matched healthy controls (n=7). Two different tasks
      (prosaccades and pursuit) were used to examine functions necessary for the
      planning and execution of eye movements. Student's t-test was used for the
      statistical analysis. RESULTS: Prosaccades were able to be recorded in five
      children with ADHD and in all control subjects. In two patients, no saccades
      could be recorded due to their hyperactivity. There were significant differences
      (P<0.01) in prosaccade latency, children with ADHD showing significantly longer
      latency on the prosaccade task than controls (299+/-91 ms versus 197+/-14 ms).
      Pursuit performance was saccadic with a gain of 0.4 versus 0.6 and was not
      significantly altered in the ADHD group with respect to controls. CONCLUSION:
      Oculomotor measurements can be a simple, non-invasive test, easily performed in
      children with ADHD. Longer latency on the prosaccade task is observed in ADHD
      children.

PMID- 22634027
TI  - [Bacterial endophthalmitis: retrospective clinical and microbiological study in
      Rabat Specialty Hospital].
AB  - OBJECTIVES: To study and discuss the epidemiological, clinical, microbiological,
      and risk factors of bacterial endophthalmitis treated in the Rabat Specialty
      Hospital ophthalmology department. PATIENTS AND METHODS: This is a retrospective
      study over a period of 10 months of patients hospitalized for suspected acute
      infectious endophthalmitis. An intake form was completed for each patient. Each
      sample underwent direct examination and culture. All patients underwent the same
      protocol, providing for at least one intravitreal antibiotic injection and
      instillation of fortified eye drops. RESULTS: Twenty cases of endophthalmitis
      were recorded during the study period. Decreased visual acuity, intraocular
      inflammation, pain and conjunctival hyperemia were found in all patients. The
      median onset of symptoms was 4 days. Vitreous tap or anterior chamber
      paracentesis was performed in all patients. Bacteria were found in seven samples
      (40%). Gram positive organisms accounted for 85% of positive cultures.
      Amphotericin B was required in four patients, and systemic antibiotic therapy in
      ten patients. Corticosteroid treatment was administered secondarily in eight
      patients. DISCUSSION: In this retrospective series, epidemiological, clinical and
      microbiological data are consistent with those already published.

PMID- 22634028
TI  - Isotopic ratio and vertical distribution of radionuclides in soil affected by the
      accident of Fukushima Dai-ichi nuclear power plants.
AB  - The results of gamma analyses of soil samples obtained from 50 locations in
      Fukushima prefecture on April 20, 2011, revealed the presence of a spectrum of
      radionuclides resulted from the accident of the Fukushima Dai-ichi nuclear power
      plant (FDNPP). The sum gamma radioactivity concentration ranged in more than 3
      orders of magnitude, depending on the sampling locations. The contamination of
      soils in the northwest of the FDNPP was considerable. The (131)I/(137)Cs activity
      ratios of the soil samples plotted as a function of the distance from the F1 NPPs
      exhibited three distinctive patterns. Such patterns would reflect not only the
      different deposition behaviors of these radionuclides, but also on the conditions
      of associated release events such as temperature and compositions and
      physicochemical forms of released radionuclides. The (136)Cs/(137)Cs activity
      ratio, on the other hand, was considered to only reflect the difference in
      isotopic compositions of source materials. Two locations close to the NPP in the
      northwest direction were found to be depleted in short-lived (136)Cs. This likely
      suggested the presence of distinct sources with different (136)Cs/(137)Cs
      isotopic ratios, although their details were unknown at present. Vertical gamma
      activity profiles of (131)I and (137)Cs were also investigated, using 20-30 cm
      soil cores in several locations. About 70% or more of the radionuclides were
      present in the uppermost 2-cm regions. It was found that the profiles of
      (131)I/(137)Cs activity ratios showed maxima in the 2-4 cm regions, suggesting
      slightly larger migration of the former nuclide.

PMID- 22634029
TI  - Measuring effective radium concentration with less than 5 g of rock or soil.
AB  - Radon generation in natural systems and building materials is controlled by the
      effective radium concentration EC(Ra), product of the radium concentration C(Ra)
      and the emanation factor E. An experimental method is proposed to measure EC(Ra)
      in the laboratory by radon accumulation experiments using less than 5 g of sample
      inserted in 125 mL scintillation flasks. Accumulation curves with fine temporal
      resolution can be obtained, allowing the simultaneous determination of the
      effective leakage rate. The detection limit, defined as the EC(Ra) value giving a
      probability larger than 90% for a determination with a one-sigma uncertainty
      better than 50%, is moderate, varying from 2 to 5 Bq kg(-1) depending on the
      conditions. Obtained punctual uncertainties on EC(Ra) vary from about 10 to 20%
      at 10 Bq kg(-1) to less than 3% for EC(Ra) larger than 500 Bq kg(-1). The
      representativity of small samples to estimate meaningful values at site or system
      level is, however, a definite limitation of the method, and the sample dispersion
      needs to be considered carefully in every case. Nevertheless, the value obtained
      with 5 g or less differs on average by 9 +/- 13% from the value given by standard
      methods using 100 g or more, thus is sufficiently reliable for most applications.
      When EC(Ra) is sufficiently large, the temperature sensitivity of EC(Ra) can be
      measured reliably with this method, with obtained mean values ranging from 0.39
      +/- 0.05%  degrees C(-1) for Compreignac granite, to 2.8 +/- 0.2%  degrees C(-1)
      for La Crouzille pitchblende, both from the centre of France. This method is
      useful to study dedicated problems, such as the small scale variability of
      EC(Ra), and in circumstances when only a small amount of sample is available, for
      example from remote areas or from precious materials such as historical building
      stones.

PMID- 22634030
TI  - Histological variations in liver of freshwater fish Oreochromis mossambicus
      exposed to 60Co gamma irradiation.
AB  - The irradiation effect of (60)Co at the three dose level of 3 mGy, 30 mGy and 300
      mGy on the histology of liver of the freshwater fish Oreochromis mossambicus was
      investigated. The liver of O. mossambicus was dissected out and processed for
      light microscopy studies. (60)Co exposed O. mossambicus were found to result in
      several alterations in the histoarchitecture of liver. The alterations included
      mild congestion of blood vessels, structural alteration, cellular swelling,
      vacuolation and necrotic liver cells, indicating a definite response to (60)Co
      irradiation. The results suggest that the liver of O. mossambicus exposed to
      (60)Co were structurally altered with increasing dose levels. It is to record
      that alteration in the liver does not affect the physiology, behaviour or
      lethality of the individuals. Self regulating mechanisms would have influenced
      the liver to remain sustained. To confirm the same further studies in the
      direction by increasing dose level is required.

PMID- 22634031
TI  - Real-time analysis of the interaction of a multiple-epitope peptide with
      antibodies against classical swine fever virus using surface plasmon resonance.
AB  - The E2 envelope glycoprotein is the major immunodominant protein of classical
      swine fever virus (CSFV), and can induce neutralizing antibodies and protective
      immune responses in infected swine. We developed a tandem-repeat multiple-epitope
      recombinant protein that contains two copies of each of the regions of E2 spanned
      by residues 693-704, 770-780, and 826-843, coupled by two copies of the region
      spanned by residues 1446-1460 of the CSFV nonstructural protein NS2-3. The
      chemically synthesized gene was expressed in Escherichia coli as a fusion with
      glutathione S-8 (GST), named GST-BT21. After it was purified with Glutathione
      Sepharose 4B, we used Western blotting to characterize the construct and surface
      plasmon resonance to analyze its affinity and specific interaction with CSFV
      positive serum. Purified GST-BT21 protein displayed excellent immunoreactivity
      with antiserum against CSFV (Tian et al., 2012), and surface plasmon resonance
      confirmed the specific affinity between BT21, but not GST, and antibodies in
      serum from animals infected with CSFV. Surface plasmon resonance is a sensitive
      and precise method for epitope evaluation, and it can be used to characterize the
      immunogenicity and functions of recombinant proteins.

PMID- 22634032
TI  - An update on the Conceptual-Production Systems model of apraxia: evidence from
      stroke.
AB  - Limb apraxia is a neurological disorder characterized by an inability to
      pantomime and/or imitate gestures. It is more commonly observed after left
      hemisphere damage (LHD), but has also been reported after right hemisphere damage
      (RHD). The Conceptual-Production Systems model (Roy, 1996) suggests that three
      systems are involved in the control of purposeful movements: the conceptual, the
      production and the sensory/perceptual system. Depending on which system is
      damaged different patterns of apraxia are expressed. To determine the apraxia
      pattern, pantomime, delayed, and concurrent imitation tasks need to be
      administered, as well as conceptual tasks assessing one's knowledge of actions.
      Based on the model, eight patterns of apraxia should emerge. The purpose of this
      study is to determine whether these patterns are in fact observed in stroke
      patients and examine their frequency. If the performance of most stroke patients
      falls into one of the patterns, then we would have strong support for the
      conceptual-production model. Stroke (34 LHD and 39 RHD) patients and 27 age- and
      education-matched healthy controls participated in the study. Participants were
      assessed in four task modalities: pantomime, delayed imitation, concurrent
      imitation and conceptual knowledge (two tasks were used: tool naming by action
      and action identification). Patients were categorized as impaired on a task if
      they scored 2 SD below the mean performance of the controls for gesture
      production tasks, or below a cut-off score on the conceptual tasks. They were
      then classified into patterns depending on their performance on the four task
      modalities. Most patients (86%) fell into one of seven patterns originally
      predicted from the Conceptual-Production Systems model. The two most common
      patterns were deficits in pantomime and imitation with preserved gesture
      recognition and conduction apraxia (selective deficit in imitation). Four new
      patterns emerged, but mostly single cases of these were found. Overall, the study
      provides strong support for the Conceptual-Production Systems model.

PMID- 22634033
TI  - One hand, two objects: emergence of affordance in contexts.
AB  - Studies on affordances typically focus on single objects. We investigated whether
      affordances are modulated by the context, defined by the relation between two
      objects and a hand. Participants were presented with pictures displaying two
      manipulable objects linked by a functional (knife-butter), a spatial (knife
      coffee mug), or by no relation. They responded by pressing a key whether the
      objects were related or not. To determine if observing other's actions and
      understanding their goals would facilitate judgments, a hand was: (a) displayed
      near the objects; (b) grasping an object to use it; (c) grasping an object to
      manipulate/move it; (d) no hand was displayed. RTs were faster when objects were
      functionally rather than spatially related. Manipulation postures were the
      slowest in the functional context and functional postures were inhibited in the
      spatial context, probably due to mismatch between the inferred goal and the
      context. The absence of this interaction with foot responses instead of hands in
      Experiment 2 suggests that effects are due to motor simulation rather than to
      associations between context and hand-postures.

PMID- 22634034
TI  - Event-related EEG oscillations to semantically unrelated words in normal and
      learning disabled children.
AB  - Learning disabilities (LD) are one of the most frequent problems for elementary
      school-aged children. In this paper, event-related EEG oscillations to
      semantically related and unrelated pairs of words were studied in a group of 18
      children with LD not otherwise specified (LD-NOS) and in 16 children with normal
      academic achievement. We propose that EEG oscillations may be different in LD NOS
      children versus normal control children that may explain some of the deficits
      observed in the LD-NOS group. The EEGs were recorded using the 10/20 system. EEG
      segments were edited by visual inspection 1000ms before and after the stimulus,
      and only correct responses were considered in the analysis. Time-frequency (1
      50Hz) topographic maps were obtained for the increases and decreases of power
      after the event with respect to the pre-stimulus average values. Significant
      differences between groups were observed in the behavioral responses. LD-NOS
      children show less number of correct responses and more omissions and false
      alarms than the control group. The event-induced EEG responses showed significant
      differences between groups. The control group showed greater power increases in
      the frequencies 1-6Hz than the LD-NOS group from 300 to 700ms. These differences
      were mainly observed in frontal regions, both to related and non-related words.
      This was interpreted as a deficit in attention, both to internal and external
      events, deficits in activation of working memory and deficits in encoding and
      memory retrieval in the LD-NOS children. Differences between groups were also
      observed in the suppression of alpha and beta rhythms in the occipital regions to
      related words in frequencies between 8 and 17Hz from 450 to 750ms. LD-NOS
      children showed shorter durations of the decreases in power than the control
      group. These results suggest also deficits in attention and memory retrieval. It
      may be concluded that LD-NOS children showed physiological differences from
      normal children that may explain their cognitive deficiencies.

PMID- 22634035
TI  - Mutations within the human parainfluenza virus type 3 (HPIV 3) C protein affect
      viral replication and host interferon induction.
AB  - Human parainfluenza virus type 3 (HPIV 3) encodes a multifunctional C protein
      that is capable of inhibiting viral replication and counteracting the host
      interferon (IFN) signaling pathway. We recently demonstrated that the C protein
      is phosphorylated both in vitro and in vivo and mutations within the
      phosphorylation sites exhibit differential inhibitory activities in vitro. In
      this study, we report for the first time the successful recovery of mutant HPIV 3
      viruses containing mutations within the C protein. Three mutant viruses, Cm-1, Cm
      3 and Cm-4, harboring individual mutations of S7, S47T48 and S81 residues,
      respectively, were examined for their replication profiles and their ability to
      abrogate host IFN induction. Viral transcription was similar for all viruses;
      however Cm-3 displayed a relatively higher replication. Infection of cells with
      Cm-1 and Cm-3 led to the activation of IFN regulatory transcription factor 3 (IRF
      3) and subsequent increase in IFN-beta mRNA levels as determined by
      immunofluorescence assay and RT-PCR analyses, respectively. Moreover, Cm-3 was
      able to partially resist the interferon induced antiviral state in Vero cells.
      Taken together, these results suggest that mutations within the C protein
      differentially affect viral replication and host interferon induction.

PMID- 22634036
TI  - Dissecting the Ca2+ entry pathways induced by rotavirus infection and NSP4-EGFP
      expression in Cos-7 cells.
AB  - Rotavirus infection modifies Ca(2+) homeostasis provoking an increase in Ca(2+)
      permeation, cytoplasmic Ca(2+) concentration ([Ca(2+)](cyto)), total Ca(2+) pools
      and, a decrease of Ca(2+) response to agonists. These effects are mediated by
      NSP4. The mechanism by which NSP4 deranges Ca(2+) homeostasis is not yet known.
      It has been proposed that the increase in [Ca(2+)](cyto) is the result of Ca(2+)
      release from intracellular stores, thereby activating store-operated Ca(2+) entry
      (SOCE). We studied the mechanisms involved in the changes of Ca(2+) permeability
      of the plasma membrane elicited by rotavirus infection and NSP4 expression in Cos
      7 cells loaded with fura-2 or fluo-4, using inhibitors and activators of
      different pathways. Total depletion of ER Ca(2+) stores induced by thapsigargin
      or ATP was not able to elicit Ca(2+) entry in mock-infected cells to the level
      attained with infection or NSP4-EGFP expression. The pathway induced by NSP4-EGFP
      expression or infection shows properties shared by SOCE: it can be inactivated by
      high [Ca(2+)](cyto), is permeable to Mn(2+) and inhibited by La(3+) and the SOC
      inhibitor 2-aminoethoxydiphenyl borate (2-APB). Contribution of the agonist
      operated channels (AOCs) to Ca(2+) entry is small and not modified by infection.
      The plasma membrane permeability to Ca(2+) in rotavirus infected or NSP4-EGFP
      expressing cells is also blocked by KB-R7943, an inhibitor of the plasma membrane
      Na(+)/Ca(2+) exchanger (NCX), operating in its reverse mode. In conclusion, the
      expression of NSP4 in infected Cos-7 cells appears to activate the NCX in reverse
      mode and the SOCE pathway to induce increased Ca(2+) entry.

PMID- 22634037
TI  - HSV-2 inhibits type-I interferon signaling via multiple complementary and
      compensatory STAT2-associated mechanisms.
AB  - Type-I interferon (IFN)-mediated responses are a crucial first line of defense
      against viral infections and are critical for generating both innate and adaptive
      immunity. Therefore, viruses have necessarily evolved mechanisms to impede the
      IFN response. HSV-2 was found to completely abolish type-1 IFN-mediated signaling
      via multiple STAT2-associated mechanisms. Although the extent and kinetics of
      this inactivation were indistinguishable between the various cell-lines examined,
      there were distinct differences in the mechanisms HSV-2 employed to subvert IFN
      signaling among the cell-lines. These mechanistic differences could be segregated
      into two categories dependent on the phase of the HSV replicative cycle that was
      responsible for this inhibition: (1) early phase-inhibited cells which exhibited
      abrogation of IFN-signaling prior to viral DNA replication; (2) late phase
      inhibited cells where early phase inhibition mechanisms were not functional, but
      viral functions expressed following DNA replication compensated for their
      ineffectiveness. In early phase-inhibited cells, HSV-2 infection targeted STAT2
      protein for proteosomal degradation and prevented de novo expression of STAT2 by
      degrading its mRNA. In contrast, HSV-2 infected late phase-inhibited cells
      exhibited no apparent changes in STAT2 transcript or protein levels. However, in
      these cells STAT2 was not activated by phosphorylation and failed to translocate
      to the cell nucleus, thereby preventing transactivation of antiviral genes. In
      primary human fibroblasts, HSV-2 failed to fully degrade STAT2 and therefore,
      both early and late phase mechanisms functioned cooperatively to subvert IFN
      mediated antiviral gene expression. Taken together, these results indicate the
      importance that HSV-2 has assigned to STAT2, investing significant genomic
      currency throughout its replicative lifecycle for continuous targeted destruction
      and inhibition of this protein.

PMID- 22634038
TI  - Effect of inactivation of ccpA and aerobic growth in Lactobacillus plantarum: A
      proteomic perspective.
AB  - Lactobacillus plantarum is a facultative heterofermentative lactic acid bacterium
      widely used in the production of most fermented food due to its ability to thrive
      in several environmental niches, including the human gut. In order to cope with
      different growth conditions, it has developed complex molecular response
      mechanisms, characterized by the induction of a large set of proteins mainly
      regulated by HrcA and CtsR repressors as well as by global regulators such as
      carbon catabolite control protein A (CcpA). In this study, the role of CcpA in
      the regulation of growth under anaerobiosis and aerobiosis, and the adaptation to
      aeration in L. plantarum WCFS1 were comprehensively investigated by differential
      proteomics. The inactivation of ccpA, in both growth conditions, significantly
      changed the expression level of 76 proteins, mainly associated with carbohydrate
      and energy metabolism, membrane transport, nucleotide metabolism, protein
      biosynthesis and folding. The role of CcpA as pleiotropic regulator was
      particularly evident at the shift from homolactic fermentation to mixed
      fermentation. Proteomic results also indicated that the mutant strain was more
      responsive to aerobic growth condition.

PMID- 22634039
TI  - Proteomic analysis of strawberry leaves infected with Colletotrichum fragariae.
AB  - Understanding the defense mechanisms used by anthracnose-resistant strawberries
      against Colletotrichum infection is important for breeding purposes. To
      characterize cell responses to Colletotrichum infection, proteomes from
      strawberry seedling leaves that had or had not been infected with Colletotrichum
      fragariae were characterized at different time points post infection by 2-DE and
      by MALDI-TOF/TOF MS/MS and database-searching protein identification. Mass
      spectrometry identified 49 differentially expressed proteins with significant
      intensity differences (>1.5-fold, p<0.05) in mock- and C. fragariae-infected
      leaves at least at one time point. Notably, 2-DE analysis revealed that C.
      fragariae infection increased the expression of well-known and novel pathogen
      responsive proteins whose expression patterns tended to correlate with
      physiological changes in the leaves. Quantitative real-time PCR was used to
      examine the transcriptional profiles of infected and uninfected strawberry
      leaves, and western blotting confirmed the induction of beta-1,3-glucanase and a
      low-molecular-weight heat shock protein in response to C. fragariae infection.
      During the late phase of infection, proteins involved in the Calvin cycle and
      glycolysis pathway had suppressed expression. The abundance changes, putative
      functions, and participation in physiological reactions for the identified
      proteins produce a pathogen-responsive protein network in C. fragariae-infected
      strawberry leaves. Together, these findings increase our knowledge of pathogen
      resistance mechanisms, especially those found in non-model plant species.

PMID- 22634040
TI  - Differential proteome analysis of a selected bacterial strain isolated from a
      high background radiation area in response to radium stress.
AB  - The present study describes the response of a bacterial strain, isolated from a
      hot spring in an area with the highest levels of natural radiation, under radium
      ((226)Ra) stress. The bacterium has been characterized as a novel and efficient
      radium biosorbent and identified as a variant of Serratia marcescens by
      biochemical tests and molecular recognition. In order to gain insights into key
      cellular events that allow this strain to survive and undergo (226)Ra adaptation
      and biosorption, the strain was tested under two experimental conditions of 1000
      and 6000 Bq (226)Ra stress. A proteomic approach involving two-dimensional
      polyacrylamide gel electrophoresis and mass spectrometry was used to identify the
      differentially expressed proteins under (226)Ra stress. Functional assessment of
      identified proteins with significantly altered expression levels revealed several
      mechanisms thought to be involved in (226)Ra adaptation and conferring resistant
      phenotype to the isolate, including general stress adaptation, anti-oxidative
      stress, protein and nucleic acid synthesis, energy metabolism, efflux and
      transport proteins. It suggests that this strain through evolution is
      particularly well adapted to the high background radiation environment and could
      represent an alternative source to remove (226)Ra from such areas as well as
      industrial radionuclide polluted wastewaters.

PMID- 22634041
TI  - Proteomics of inflammatory and oxidative stress response in cows with subclinical
      and clinical mastitis.
AB  - Cow serum proteome was evaluated by three different complementary approaches in
      the control group, subclinical and clinical mastitis in order to possibly find
      differential protein expression useful for a better understanding of the
      pathophysiology of mastitis as well as for an early diagnosis of the disease. The
      systemic inflammatory and oxidative stress response in cows with subclinical and
      clinical mastitis were observed. The collected evidence shows a differential
      protein expression of serpin A3-1, vitronectin-like protein and complement factor
      H in subclinical mastitis in comparison with the control. It was also found a
      differential protein expression of inter-alpha-trypsin inhibitor heavy chain H4,
      serpin A3-1, C4b-binding protein alpha chain, haptoglobin and apolipoprotein A-I
      in clinical mastitis compared to the control. Among the inflammatory proteins up
      regulated in clinical mastitis, vitronectin is over-expressed in both subclinical
      and clinical mastitis indicating a strong bacterial infection. This suggests
      vitronectin as an important mediator in the pathogenesis of the onset of mastitis
      as well as a valuable marker for diagnosis of the subclinical form of the
      disease. Obtained data could be useful for the detection of mastitis during the
      subclinical phase and for a better comprehension of the pathophysiological
      mechanisms involved in the onset of the disease.

PMID- 22634042
TI  - Identification of differentially expressed proteins involved in the early larval
      development of the Pacific oyster Crassostrea gigas.
AB  - The trochophore and D-veliger are two pivotal but distinct developmental stages
      in bivalve larval development. Complex morphological and physiological processes
      are involved in the transition between these stages, yet the underlying molecular
      mechanisms remain largely elusive. In this study, a comparative proteomic
      analysis was conducted to identify the proteins related to early larval
      development of the Pacific oyster Crassostrea gigas. Fifty proteins showing
      different levels of expression were screened. These spots were further analyzed
      using LC-MS/MS and twenty of them were identified. Together with information from
      Western blotting and real-time PCR assay of some annotated genes, our results
      provide insight into novel aspects of cellular processes and protein function in
      oyster larvae. For example, it was shown that cell division was unexpectedly
      slowed down in D-veliger larvae, while substantial gene transcription and
      biochemical activity were revealed. "Quality control" proteins were identified
      for the first time to be involved in mollusk larval development. Bivalve larval
      development provides an elegant system for studying cellular processes and tissue
      morphogenesis. Our data shed light on the molecular mechanisms underlying these
      complex processes and regulatory networks.

PMID- 22634043
TI  - Proteome analysis of the farnesol-induced stress response in Aspergillus nidulans
      -The role of a putative dehydrin.
AB  - The isoprenoid alcohol farnesol represents a quorum-sensing molecule in
      pathogenic yeasts, but was also shown to inhibit the growth of many filamentous
      fungi. In order to gain a deeper insight into the antifungal activity of
      farnesol, we performed 2D-differential gel electrophoretic analysis (2D-DIGE) of
      Aspergillus nidulans exposed to farnesol. We observed an increased abundance of
      antioxidative enzymes and proteins involved in protein folding and the ubiquitin
      mediated protein degradation. A striking finding was the strong up-regulation of
      a dehydrin-like protein (DlpA). Expression analyses suggested the involvement of
      DlpA in the cellular response to oxidative, osmotic and cold stress. In line with
      these data, we demonstrated that dlpA expression was regulated by the MAP kinase
      SakA/HogA. The generation of both a dlpA Tet(on) antisense RNA-producing A.
      nidulans strain (dlpA-inv) and a DeltadlpA deletion mutant indicated a role of
      DlpA in conidiation and stress resistance of dormant conidia against heat and
      ROS. Furthermore, the production of the secondary metabolite sterigmatocystin was
      absent in both strains dlpA-inv and DeltadlpA. Our results demonstrate the
      complexity of the farnesol-mediated stress response in A. nidulans and describe a
      farnesol-inducible dehydrin-like protein that contributes to the high tolerance
      of resting conidia against oxidative and heat stress.

PMID- 22634044
TI  - Larval starvation reduces responsiveness to feeding stimuli and does not affect
      feeding preferences in a butterfly.
AB  - It is commonly assumed that holometabolic insects such as Lepidoptera rely
      primarily on larval storage reserves for reproduction. Recent studies though have
      documented a prominent role of adult-derived carbohydrates for butterfly
      reproduction. Moreover, a few studies have shown that adult butterflies may also
      benefit from adult-derived amino acids, at least when larval storage reserves are
      reduced. Given that in holometabolous insects larval deficiencies are carried
      over into the adult stage, reduced storage reserves have the potential to
      modulate adult feeding preferences and responses in order to allow for a
      successful compensation. We tested this hypothesis here in the fruit-feeding
      butterfly Bicyclus anynana using larval food stress to manipulate storage
      reserves. Alcohols (methanol, ethanol, butanol, propanol), sugars (maltose,
      glucose, fructose, sucrose), and acetic acid acted as feeding stimuli, while
      butterflies did not respond to other substances such as amino acids, yeast,
      salts, or vitamins. Contrary to expectations, stressed butterflies showed a
      weaker response than controls to several feeding stimuli. In preference tests,
      butterflies preferred sugar solutions containing proline, arginine, glutamic
      acid, acetic acid, or ethanol over plain sugar solutions, but discriminated
      against salts. However, there were no general differences among starved and
      control butterflies. We conclude that larval food-stress does not elicit
      compensatory feeding behavior such as a stronger preference for amino acids or
      other essential nutrients in B. anynana. Instead, the stress imposed by a period
      of starvation yielded negative effects.

PMID- 22634045
TI  - Seasonal variation in the titers and biosynthesis of the primer pheromone ethyl
      oleate in honey bees.
AB  - Honey bees allocate tasks along reproductive and non-reproductive lines: the
      queen mates and lays eggs, whereas the workers nurse the brood and forage for
      food. Among workers, tasks are distributed according to age: young workers nurse
      and old workers fly out and forage. This task distribution in the colony is
      further regulated by an increase in juvenile hormone III as workers age and by
      pheromones. One such compound is ethyl oleate (EO), a primer pheromone that
      delays the onset of foraging in young workers. EO is produced by foragers when
      they are exposed to ethanol (from fermented nectar) while gathering food. EO is
      perceived by younger bees via olfaction. We describe here the seasonal variation
      of EO production and the effects of Methoprene, a juvenile hormone analog. We
      found that honey bee workers biosynthesize more EO during the growing season than
      during the fall and winter months, reaching peak levels at late spring or summer.
      When caged workers were fed with syrup+d(6)-ethanol, labeled EO accumulated in
      the honey crop and large amounts exuded to the exoskeleton. Exuded levels were
      high for several hours after exposure to ethanol. Treatment with Methoprene
      increased the production of EO in worker bees, by speeding up its movement from
      biosynthetic sites to the exoskeleton, where EO evaporates. Crop fluid from bees
      collected monthly during the growing season showed a modest seasonal variation of
      in vitro EO biosynthetic activity that correlated with the dry and sunny periods
      during which bees could forage.

PMID- 22634046
TI  - Foraging strategy switching in an antlion larva.
AB  - Antlion larvae are typically considered as trap-building predators, but some
      species of antlions always forage without using pits or only sometimes use pits
      to capture prey; they can ambush prey without pits. This study examined a species
      that switches its strategy between pit-trapping and ambushing and asked the
      mechanism behind the switching behaviour. A dynamic optimization model
      incorporating tradeoffs between the two strategies was built. The tradeoffs were
      prey capture success and predation risk (both are higher when pit-trapping). The
      model predicted that antlions should use the trap-building strategy when their
      energy status is low and should use the ambush strategy when their energy status
      is high. These predictions as well as an assumption (i.e., predation risk
      associated with pit-trapping is higher than that associated with ambushing) of
      the model were empirically confirmed. The results suggest that antlions flexibly
      switch between pit-trapping and ambushing to maximize their fitness by balancing
      the costs and benefits of the two strategies.

PMID- 22634047
TI  - Carrier-mediated transport of quercetin conjugates: involvement of organic anion
      transporters and organic anion transporting polypeptides.
AB  - Flavonoids modulate cell signaling and inhibit oxidative enzymes. After oral
      consumption, they circulate in human plasma as amphiphilic glucuronide or sulfate
      conjugates, but it is unknown how these physiological metabolites permeate into
      cells. We examined the mechanisms of uptake of these conjugates into
      hepatocellular carcinoma (HepG2) cells, and found that uptake of quercetin-3'-O
      sulfate was saturable and temperature-dependent, indicating the involvement of
      carrier-mediated transport. Quercetin-3-O-glucuronide was taken up predominantly
      via passive diffusion in these cells. Quantitative real-time PCR analysis showed
      high expression of OATP4C1, followed by OAT2, OAT4 and low expression of OATP1B1
      in HepG2 cells, and addition of inhibitors of OATs and OATPs resulted in a
      significant reduction in quercetin-3'-O-sulfate uptake. The accumulation of
      quercetin-3'-O-sulfate was further evaluated in HEK293 cells expressing OAT2,
      OAT4 and OATP4C1. Uptake of quercetin-3'-O-sulfate was 2.3- and 1.4-fold higher
      in cells expressing OAT4 and OATP4C1 at pH 6.0, respectively, than in control
      HEK293 cells. siRNA knockdown of OATP4C1 expression in HepG2 cells reduced uptake
      of quercetin-3'-O-sulfate by ~40%. This study highlights a role for OATs and
      OATPs in the cellular uptake of biologically active flavonoid conjugates.

PMID- 22634048
TI  - beta,beta-Dimethylacrylshikonin exerts antitumor activity via Notch-1 signaling
      pathway in vitro and in vivo.
AB  - beta,beta-Dimethylacrylshikonin (DA) is a major component of Radix Lithospermum
      erythrorhizon and has various biological activities. We have investigated the
      inhibitory effect of DA on the growth of hepatocellular carcinoma in vitro and in
      vivo. Notch signaling plays a critical role in maintaining the balance between
      cell proliferation, differentiation and apoptosis. Hence, perturbed Notch
      signaling may contribute to tumorigenesis. In the present study, we evaluated
      whether DA could be an effective inhibitor on cell growth in human gastric cancer
      cell line, and also the molecular mechanisms. Using multiple cellular and
      molecular approaches such as MTT assay, colony formation assay, DAPI staining,
      flow cytometry, real-time PCR and Western blot analysis, we found that DA
      inhibited cell growth in a dose- and time-dependent manner. Biochemical analysis
      revealed the involvement of cell cycle regulated proteins in DA-mediated of G0-G1
      arrest of SGC-7901 cells. Furthermore, DA treatment led to reduced Notch-1
      activation, expression of Jagged-1 and its downstream target Hes-1 in vitro and
      in vivo. Our data demonstrated that DA is a potent inhibitor of progression of
      gastric cancer cells, which could be due to attenuation of Notch-1. We also
      suggest that DA could be further developed as a potential therapeutic agent for
      the treatment of gastric cancer.

PMID- 22634049
TI  - Statins increase cytochrome P450 4F3-mediated eicosanoids production in human
      liver cells: a PXR dependent mechanism.
AB  - In the present study, the ability of lovastatin, a competitive inhibitor of HMG
      CoA reductase, to regulate the gene expression and function of Cytochrome P450
      4F3B (CYP4F3B) was examined in the well differentiated HepaRG human hepatoma cell
      line. Statins induced CYP4F3B mRNA, protein and the production of 20
      hydroxyeicosatetraenoic acid (20-HETE), a product of arachidonic acid metabolism
      and a peroxisome proliferator activated receptor (PPAR) ligand. This response was
      not dependent on cholesterol shortage or on sterol regulatory element binding
      protein activation. By both a pharmacological and a siRNA approaches, we
      demonstrated that recruitment of the Pregnane X Receptor (PXR) was required to
      mediate CYP4F3 induction by lovastatin. Furthermore, the CYP4F3 gene promoter was
      transcriptionally activated by PXR, and responded to lovastatin. Finally, the
      expression of fatty acid-responsive genes was increased in response to the statin
      or 20-HETE in a CYP4F3-dependent way. We propose that metabolites produced by
      CYP4F3 could modulate lipid metabolism in response to lovastatin. These results
      suggest the existence of a novel pathway, operating in liver cells, through which
      statins could lower lipid levels.

PMID- 22634050
TI  - Epothilone B inhibits migration of glioblastoma cells by inducing microtubule
      catastrophes and affecting EB1 accumulation at microtubule plus ends.
AB  - Invasion of normal brain tissue by tumor cells is a major contributing factor to
      the recurrence of glioblastoma and its resistance to therapy. Here, we have
      assessed the efficacy of the microtubule (MT) targeting agent Epothilone B
      (patupilone) on glioblastoma cell migration, a prerequisite for invasive tumor
      cell behavior. At non-cytotoxic concentrations, patupilone inhibited glioblastoma
      cell movement, as shown by transwell cell migration, random motility and spheroid
      assays. This anti-migratory effect was associated with a reduced accumulation of
      EB1 and other MT plus end tracking proteins at MT ends and with the induction of
      MT catastrophes, while the MT growth rate and other MT dynamic instability
      parameters remained unaltered. An increase in MT catastrophes led to the
      reduction of the number of MTs reaching the leading edge. Analysis of the effect
      of patupilone on MT dynamics in a reconstituted in vitro system demonstrated that
      the induction of MT catastrophes and an alteration of EB1 accumulation at MT plus
      end are intrinsic properties of patupilone activity. We have thus demonstrated
      that patupilone antagonizes glioblastoma cell migration by a novel mechanism,
      which is distinct from suppression of MT dynamic instability. Taken together, our
      results suggest that EB proteins may represent a new potential target for anti
      cancer therapy in highly invasive tumors.

PMID- 22634051
TI  - Suppression of furin by interferon-gamma and the impact on hepatitis B virus
      antigen biosynthesis in human hepatocytes.
AB  - The roles of furin and intrahepatic cytokines in chronic heptatitis B virus (HBV)
      infection remain largely unknown. Here, we examined the relations between furin,
      IL-10, IL-12beta, interferon (IFN)-gamma, programed death (PD)-1, programed death
      ligand (PD-L)1, and the suppression of hepatitis B e antigen (HBeAg) and surface
      antigen (HBsAg) biosynthesis. Liver biopsies were performed on 20 chronically HBV
      infected (15 HBeAg-positive and 5 HBeAg-negative) patients to assess liver
      inflammation/fibrosis, and mRNA levels of furin, IL-10, IL-12beta, IFN-gamma, PD
      1, and PD-L1 were assessed by quantitative real-time PCR. IFN-gamma mRNA
      abundance was associated with lower furin mRNA levels and higher PD-1 and PD-L1
      mRNA levels in liver tissue from HBeAg-positive patients. IL-10 and IL-12beta
      mRNA levels positively correlated with IFN-gamma expression levels (P < 0.05). PD
      L1 and furin mRNA levels were further assessed in IFN-gamma-stimulated hepatoma
      cell lines with (HepG2.2.15 cells) and without (HepG2 and Huh7 cells) HBV
      replication. IFN-gamma enhanced PD-L1 expression in hepatoma cells. In HepG2.2.15
      cells, IFN-gamma further suppressed furin and HBeAg expression. Furin inhibition
      and knockdown in HepG2.2.15 cells also down-regulated HBeAg and HBsAg
      biosynthesis. These data suggest that IFN-gamma modulates the inflammatory
      response to avoid excessive hepatocyte damage through the enhancement of PD-1/PD
      L1 expression, whereas furin suppression may contribute to a reduction in
      HBeAg/HBsAg biosynthesis.

PMID- 22634054
TI  - Prepubertal children with suitable fitness and physical activity present reduced
      risk of oxidative stress.
AB  - To assess the impact of fitness status and physical activity on oxidative stress
      in prepubertal children, we measured selected biomarkers such as protein
      carbonyls (PC), lipid peroxidation products, and total nitrites, as well as the
      antioxidant system: total glutathione (TG), oxidized glutathione (GSSG), reduced
      glutathione (GSH), superoxide dismutase activity, and glutathione peroxidase. A
      total of 132 healthy children ages 7-12, at prepubertal stage, were classified
      into two groups according to their fitness level: low fitness (LF) and high
      fitness (HF). They were observed while engaged in an after-school exercise
      program, and a questionnaire was created to obtain information on their physical
      activity or sedentary habits. Plasma and red blood cells were obtained to analyze
      biomarkers. Regarding oxidative stress markers, the LF group and the sedentary
      group showed higher levels of TG and GSSG and a lower GSH/GSSG ratio than the HF
      group and the children engaged in physical activity. A negative association was
      found between PC and GSSG and TG and between TG and the GSH/GSSG ratio. Moreover,
      a negative correlation was found between GSSG and fitness, with a positive
      correlation with the GSH/GSSG ratio. TG, GSSG, and the GSH/GSSG ratio seem to be
      reliable markers of oxidative stress in healthy prepubertal children with low
      fitness or sedentary habits. This research contributes to the recognition that an
      adequate level of fitness and recreational physical activity in childhood leads
      to better health and oxidative status.

PMID- 22634053
TI  - Paraoxonase 2 decreases renal reactive oxygen species production, lowers blood
      pressure, and mediates dopamine D2 receptor-induced inhibition of NADPH oxidase.
AB  - The dopamine D(2) receptor (D(2)R) regulates renal reactive oxygen species (ROS)
      production, and impaired D(2)R function results in ROS-dependent hypertension.
      Paraoxonase 2 (PON2), which belongs to the paraoxonase gene family, is expressed
      in various tissues, acting to protect against cellular oxidative stress. We
      hypothesized that PON2 may be involved in preventing excessive renal ROS
      production and thus may contribute to maintenance of normal blood pressure.
      Moreover, D(2)R may decrease ROS production, in part, through regulation of PON2.
      D(2)R colocalized with PON2 in the brush border of mouse renal proximal tubules.
      Renal PON2 protein was decreased (-33+/-6%) in D(2)(-/-) relative to D(2)(+/+)
      mice. Renal subcapsular infusion of PON2 siRNA decreased PON2 protein expression
      (-55%), increased renal oxidative stress (2.2-fold), associated with increased
      renal NADPH oxidase expression (Nox1, 1.9-fold; Nox2, 2.9-fold; and Nox4, 1.6
      fold) and activity (1.9-fold), and elevated arterial blood pressure (systolic,
      134+/-5 vs 93+/-6mmHg; diastolic, 97+/-4 vs 65+/-7mmHg; mean 113+/-4 vs 75+/
      7mmHg). To determine the relevance of the PON2 and D(2)R interaction in humans,
      we studied human renal proximal tubule cells. Both D(2)R and PON2 were found in
      nonlipid and lipid rafts and physically interacted with each other. Treatment of
      these cells with the D(2)R/D(3)R agonist quinpirole (1MUM, 24h) decreased ROS
      production (-35+/-6%), associated with decreased NADPH oxidase activity (-32+/
      3%) and expression of Nox2 (-41+/-7%) and Nox4 (-47+/-8%) protein, and increased
      expression of PON2 mRNA (2.1-fold) and protein (1.6-fold) at 24h. Silencing PON2
      (siRNA, 10nM, 48h) not only partially prevented the quinpirole-induced decrease
      in ROS production by 36%, but also increased basal ROS production (1.3-fold),
      which was associated with an increase in NADPH oxidase activity (1.4-fold) and
      expression of Nox2 (2.1-fold) and Nox4 (1.8-fold) protein. Inhibition of NADPH
      oxidase with diphenylene iodonium (10MUM/30 min) inhibited the increase in ROS
      production caused by PON2 silencing. Our results suggest that renal PON2 is
      involved in the inhibition of renal NADPH oxidase activity and ROS production and
      contributes to the maintenance of normal blood pressure. PON2 is positively
      regulated by D(2)R and may, in part, mediate the inhibitory effect of renal D(2)R
      on NADPH oxidase activity and ROS production.

PMID- 22634055
TI  - Role of sulfiredoxin as a regulator of peroxiredoxin function and regulation of
      its expression.
AB  - Peroxiredoxins (Prxs) constitute a family of peroxidases in which cysteine serves
      as the primary site of oxidation during the reduction of peroxides. Members of
      the 2-Cys Prx subfamily of Prxs (Prx I to IV in mammals) are inactivated via
      hyperoxidation of the active-site cysteine to sulfinic acid (Cys-SO(2)H) during
      catalysis and are reactivated via an ATP-consuming reaction catalyzed by
      sulfiredoxin (Srx). This reversible hyperoxidation reaction has been proposed to
      protect H(2)O(2) signaling molecules from premature removal by 2-Cys Prxs or to
      upregulate the chaperone function of these enzymes. In addition to its sulfinic
      acid reductase activity, Srx catalyzes the removal of glutathione
      (deglutathionylation) from modified proteins. The physiological relevance of both
      the reversible hyperoxidation of 2-Cys Prxs and the deglutathionylation catalyzed
      by Srx remains unclear. Recent findings have revealed that Srx expression is
      induced in mammalian cells under a variety of conditions, such as in
      metabolically stimulated pancreatic beta cells, in immunostimulated macrophages,
      in neuronal cells engaged in synaptic communication, in lung cells exposed to
      hyperoxia or cigarette smoke, in hepatocytes of ethanol-fed animals, and in
      several types of cells exposed to chemopreventive agents. Such induction of Srx
      in mammalian cells is regulated at the transcriptional level, predominantly via
      activator protein-1 and/or nuclear factor erythroid 2-related factor 2. Srx
      expression is also regulated at the translational level in Saccharomyces
      cerevisiae.

PMID- 22634056
TI  - Long-term cortisol in bipolar disorder: associations with age of onset and
      psychiatric co-morbidity.
AB  - INTRODUCTION: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is
      hypothesized to play a role in the pathogenesis of bipolar disorder (BD).
      Conflicting results have been reported when saliva or serum was used to measure
      cortisol levels. A recently developed method is to measure cortisol in scalp
      hair, with 1cm of scalp hair representing 1 month. We studied whether there are
      differences in long-term hair cortisol levels between BD patients and healthy
      individuals and whether there are associations between hair cortisol and disease
      characteristics. METHODS: Hair samples were collected in 100 BD patients and 195
      healthy controls. Long-term cortisol levels were determined in 3 cm hair
      segments. Saliva samples were collected on two consecutive evenings. Documented
      disease characteristics were disease state, age of onset and psychiatric co
      morbidity. RESULTS: Hair cortisol levels were not statistically different in BD
      patients compared to healthy controls (p=0.233) and were not associated with the
      disease state at the moment of sample collection (p=0.978). In the subgroup of
      patients with age of onset >= 30 years, hair cortisol levels were significantly
      elevated compared to the subgroup with age of onset <30 years and to healthy
      controls (p=0.004). Psychiatric co-morbidity was associated with elevated
      cortisol levels (44.87 versus 31.41 pg/mg hair; p=0.021), with the exclusion of
      panic disorder, which was associated with decreased cortisol levels (22.13 versus
      34.67 pg/mg hair; p=0.019). CONCLUSIONS: Elevated long-term cortisol levels might
      play a role in a subgroup of patients with BD. There may be differences in
      pathogenesis of younger and older onset BD suggesting two different disease
      entities.

PMID- 22634057
TI  - Cytotoxicity induced by deltamethrin and its metabolites in SH-SY5Y cells can be
      differentially prevented by selected antioxidants.
AB  - Deltamethrin, an alpha-cyano pyrethroid insecticide, is a relatively potent
      neurotoxicant. The main deltamethrin metabolism mechanisms are ester cleavage and
      oxidation at the 2' and 4' position of the terminal aromatic ring. Although some
      aspects of the toxicity properties of deltamethrin have been reported, limited
      information is available about the metabolites cytotoxic actions. The aims of
      this study are to examine in vitro neurotoxicity of deltamethrin and its
      metabolites 3-phenoxybenzoic acid (3-PBA), 2'-OH-deltamethrin, and 4'-OH
      deltamethrin and to evaluate melatonin (0.1, 1MUM), trolox (0.3, 1MUM) and N
      acetylcysteine (500, 1000MUM) protective role in SH-SY5Y cells. MTT and neutral
      red uptake (NRU) assays were carried out to assess the cytotoxicity of
      deltamethrin and its metabolites. Of the three metabolites tested, while 3-PBA
      (0.01-1000MUM) did not show neurotoxicity, 2'-OH- and 4'-OH-deltamethrin (10
      1000MUM) were more toxic than deltamethrin (10-1000MUM). Levels of both nitric
      oxide (NO) and lipid peroxides measured as malondialdehyde were significantly
      increased in deltamethrin and 4'-OH-deltamethrin-treated cells. Compared to other
      antioxidants, 1MUM MEL treatment effectively protected against deltamethrin and
      4'-OH-deltamethrin-induced lipid peroxidation and ameliorated the NO adverse
      effect that might have been caused. These results suggest that oxidative stress
      observed is one of the major mechanisms of deltamethrin-induced neurotoxicity and
      it may be attributed in part to deltamethrin disposition and metabolism.

PMID- 22634058
TI  - The inhibition of major human hepatic cytochrome P450 enzymes by 18 pesticides:
      comparison of the N-in-one and single substrate approaches.
AB  - In the present study on human hepatic microsomes, the N-in-one assay with ten
      probe substrates for nine cytochrome-P450 enzymes (CYPs) was compared with the
      single substrate assays to investigate pesticides-CYP interactions. CYP
      inhibition was measured by liquid chromatography-tandem mass spectrometry (LC/MS
      MS). As illustrated by the initial screening at 100 MUM concentration of 18
      pesticides, CYPs are more sensitive to organophosphates (OPs) than to other
      pesticide groups. Chlorpyrifos and fenitrothion were most effective in inhibiting
      CYP1A1/2, and CYP2B6. Profenofos was also inhibitory towards multiple CYPs.
      Pyrethroids, e.g. deltamethrin, fenvalerate and lambda-cyhalothrin, potently
      inhibited CYP2D6. CYP3A4 activity was moderately inhibited by fenvalerate and
      potently by alpha-cypermethrin. The correlations between IC50 values obtained
      from the N-in-one and single substrate approaches were highly significant for
      CYP2Cs (r(2)=0.94), CYP3A4, omeprazole-sulfoxidation, (r(2)=0.89), followed by
      CYP1A2 and CYP2B6 (r(2)=0.82), and CYP2D6 (r(2)=0.80). In contrast no correlation
      was observed with CYP2E1 and CYP3A4 (midazolam-1'-hydroxylation). The N-in-one
      screening assay seems useful and reliable for most CYP activities when a
      comprehensive and quick evaluation of potential interactions with CYPs is needed.
      However, at the present moment, it does not enable discrimination on the basis of
      mechanism of inhibition. A strict comparison between single and N-in-one assays
      is a prerequisite for more extensive routine use.

PMID- 22634059
TI  - Deltamethrin inhibits osteoclast differentiation via regulation of heme oxygenase
      1 and NFATc1.
AB  - Deltamethrin is a widely used pyrethroid pesticide. Although the cytotoxicity of
      deltamethrin has been reported, especially in neuronal cells, there is no
      information concerning the effects of deltamethrin on osteoclasts (OCLs). In this
      study, we showed that deltamethrin inhibited OCL differentiation in vitro. The
      effects of deltamethrin on OCL differentiation by receptor activator of nuclear
      factor kappa-B ligand (RANKL) were investigated in bone marrow-derived
      macrophages (BMMs) or the murine monocytic cell line RAW-D. Treatment with
      deltamethrin inhibited OCL formation and bone resorption and up-regulated
      expression of heme oxygenase-1 (HO-1), an anti-oxidative stress enzyme.
      Deltamethrin also decreased the protein levels of nuclear factor of activated T
      cells cytoplasmic-1 (NFATc1), which is a master regulator for OCL
      differentiation, and concomitantly reduced the expression levels of Src and
      cathepsin K, which are transcriptionally regulated by NFATc1. The effects of
      deltamethrin on intracellular signaling during the OCL differentiation of BMMs
      indicated that deltamethrin-treated OCLs displayed impaired phosphorylation of
      extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, Jun
      N-terminal kinase, and Akt, and slightly delayed phosphorylation of inhibitor of
      nuclear factor kappa B alpha (IkappaBalpha) compared with untreated OCLs. Thus,
      deltamethrin possibly affects bone metabolism by inhibiting OCL differentiation.

PMID- 22634060
TI  - Incivility in the practice environment: a perspective from clinical nursing
      teachers.
AB  - This paper advances a notion of incivility as a precursor to a continuum of
      antisocial acts culminating in bullying behaviour. Clinical teachers (CTs),
      working with undergraduate nursing students in a variety of clinical settings
      from a large urban centre, were studied. Using a mixed method design, CTs were
      asked to define and describe the nature, type and frequency of uncivil
      encounters. Data was collected across four practice settings, which included,
      acute care, maternal child, community and mental health. To unpack the complex
      nature of incivility we applied a conceptual model based on bullying behaviour
      which permitted us to analyze CTs narratives for both form (i.e., direct vs.
      indirect incivility) and function (i.e., reactive vs. proactive). The results
      suggest that indirect incivility was the most prevalent subtype narrative
      reported. One of the implications of this study is that nurse educators can help
      new clinical students recognize the different subtypes of in/civility in the
      practice environment as an essential first step before targeted intervention
      programs can be developed and implemented to create civil learning and safer
      working environments.

PMID- 22634061
TI  - Collaboration with service users to develop reusable learning objects: the ROOT
      to success.
AB  - The involvement of service users in the education of health workers is seen as an
      important component within the curriculum. It is thought to facilitate the
      students into developing a deeper understanding around the real lives of their
      patients, and therefore ensuring their care is more person centred. The subject
      area focused upon was developing students' awareness of the needs of people with
      a learning disability. Recent incidents in the press have highlighted examples of
      poor quality care and a lack of understanding by health and social care
      professionals in regard to their needs. This article highlights a number of key
      issues which must be considered when involving service users, namely consent,
      ethical practice and collaboration. This article will describe the participation
      of service users in the development of reusable learning objects (RLO's) and make
      recommendations on the optimum way to undertake such an activity. From this
      process a framework has been developed, described as the ROOT to success. The
      ROOT element of the structure relates to Relationship, Organization, Outcome and
      Team.

PMID- 22634062
TI  - Long-term administration with levonorgestrel decreases allopregnanolone levels
      and alters GABA(A) receptor subunit expression and anxiety-like behavior.
AB  - Fluctuations in the concentrations of the neuroactive steroid allopregnanolone
      are thought to influence gamma-amino-butyric acid type A (GABA(A)) receptor gene
      expression and function. Long-term treatment with ethinyl estradiol (EE) plus
      levonorgestrel (LNG), two of the most widely used steroids in the hormonal
      contraceptive pill, decreases allopregnanolone levels in rat cerebral cortex and
      plasma, alters GABA(A) receptor expression and induces anxiety-like behavior. We
      evaluated which component of the hormonal contraceptive pill is responsible for
      the aforementioned changes. Female rats were injected subcutaneously (s.c.) with
      EE (0.030 mg) or LNG (0.125 mg) once a day for 4 weeks. Compared to the
      respective vehicle-treated control groups, EE decreased cerebral cortical levels
      of allopregnanolone, progesterone and pregnenolone by 76, 72 and 33%,
      respectively and hippocampal levels by 52, 56 and 50%, respectively. Likewise,
      LNG decreased cerebral cortical levels of allopregnanolone, progesterone and
      pregnenolone by 75, 68 and 33%, respectively, and hippocampal levels by 55, 65
      and 60%, respectively. Administration of LNG, but not EE, increased the abundance
      of the gamma2 subunit peptide in cerebral cortex and hippocampus by 38 and 59%,
      respectively. Further, LNG, but not EE, decreased the time spent and the number
      of entries into the open arms of the elevated plus maze by 56 and 43%,
      respectively, an index of anxiety-like behavior. These results suggest that
      alterations in GABA(A) receptor subunit expression and anxiety-like behavior
      induced by long-term treatment with combined EE/LNG appear to be caused by LNG.
      Given that both EE and LNG decrease allopregnanolone levels in a similar manner,
      these results further suggest that changes in allopregnanolone levels are not
      associated with GABA(A) receptor expression.

PMID- 22634063
TI  - Subsequent anxiety-related behavior in rats exposed to low-dose methadone during
      gestation, lactation or both periods consecutively.
AB  - In order to assess the long-term behavioral consequences of exposing rats to
      methadone during gestation, lactation or both periods consecutively, pregnant
      Wistar dams were provided with drinking water containing approximately 2.39
      mg/kg/day methadone. Soon after birth, litters of offspring were assigned to
      methadone-naive foster mothers. Half of these foster mothers were then provided
      with drinking water containing methadone (approximately 2.86 mg/kg/day), while
      the other half received unadulterated water. Maternal weight gain, pregnancy
      duration, litter sizes, sex ratios and average pup weights were recorded.
      Following weaning on postnatal day (PND) 28, individual rats were weighed and
      inspected for physical abnormalities and stress reactions at PND20, 60 and 120.
      At these same ages, observations were also made of the rats' behavior in an
      emergence apparatus, and an open field. Apart from a smaller number of full-term
      pregnancies, there were no effects of any type of methadone treatment on physical
      measurements recorded at any age. Nor were there any behavioral effects of
      gestational methadone experienced on its own. However, methadone experienced
      during lactation (without gestational exposure) decreased emergence speed at
      PND30, and for all testing ages combined, increased open-field ambulation (males
      only), walking, rearing and occupancy of the center of the apparatus. Exposure to
      methadone during both gestation and lactation decreased emergence latencies at
      PND30 and, for all ages combined, decreased ambulation (males only), center
      occupancy and defecation. The subsequent behavioral effects of methadone were
      largely confined to lactational exposure and, when combined with gestational
      exposure, suggested increased anxiety.

PMID- 22634064
TI  - Antidepressant-like effects of Delta9-tetrahydrocannabinol and rimonabant in the
      olfactory bulbectomised rat model of depression.
AB  - The endocannabinoid signalling system is widely accepted to play a role in
      controlling the affective state. Plant cannabinoids are well known to have
      behavioural effects in animals and humans and the cannabinoid CB(1) receptor
      antagonist rimonabant has recently been shown to precipitate depression-like
      symptoms in clinical trial subjects. The aim of the present study was to
      investigate the behavioural and neurochemical effects of chronic administration
      of Delta9-tetrahydrocannabinol (THC) and rimonabant on intact and olfactory
      bulbectomised (OB) rats used as a model of depression. As expected, OB rats were
      hyperactive in the open field. Repeated THC (2 mg/kg, i.p. once every 48 h for 21
      days) and rimonabant (5 mg/kg, i.p. once every 48 h for 21 days) reduced this
      hyperactivity, which is typical of clinically effective antidepressant drugs. In
      intact animals, chronic THC increased brain derived neurotrophic factor (BDNF)
      expression levels in the hippocampus and frontal cortex but rimonabant had no
      effect. Rimonabant increased the levels of phosphorylated extracellular signal
      regulated kinases (p-ERKs(1/2)) in the hippocampus and prefrontal cortex and THC
      also increased expression in frontal cortex. OB did not affect BDNF or p-ERK(1/2)
      expression in the hippocampus or frontal cortex and in, contrast to the intact
      animals, neither THC nor rimonabant altered expression in the OB rats. These
      findings indicate antidepressant-like behavioural properties of both THC and
      rimonabant in OB rats although additional studies are required to clarify the
      relationship between the chronic effects of cannabinoids in other pre-clinical
      models and in human depression.

PMID- 22634066
TI  - Brain responses mediating idiom comprehension: gender and hemispheric
      differences.
AB  - Processing figurative language, such as idioms, is unique in that it requires one
      to make associations between words and non-literal meanings that are contextually
      appropriate. At the neural level, processing idiomatic phrases has been linked to
      recruitment of bilateral dorsolateral prefrontal cortices (DLPFC), the left
      temporal cortex, superior medial prefrontal gyrus (MPFC), and the left inferior
      frontal gyrus (LIFG). This functional MRI study examined the brain responses
      associated with processing idiomatic compared to literal sentences. In addition,
      gender differences in neural responses associated with language comprehension
      were also explored. In an fMRI scanner, thirty-six healthy adult volunteers
      viewed sentences that were either literal or idiomatic in nature, and answered
      subsequent comprehension questions. This sentence comprehension tasks activated
      mainly prefrontal language areas (LIFG, LSFG, and RMFG). Consistent with previous
      findings, idiomatic sentences showed increased response in LIFG. These results
      are discussed in the backdrop of the graded salience hypothesis. Furthermore, we
      found gender differences in brain activation and functional connectivity during
      this task. Women showed greater overall activation than men when comprehending
      literal and idiomatic sentences; whereas men had significantly greater functional
      connectivity between LIFG and LMTG than women across tasks. Overall, the findings
      of this study highlight the gender differences in neural responses associated
      with figurative language comprehension.

PMID- 22634065
TI  - Genetic association analysis of ERBB4 polymorphisms with the risk of
      schizophrenia and SPEM abnormality in a Korean population.
AB  - The human receptor tyrosine-protein kinase erbB-4 (ERBB4) gene mediates
      neuregulin 1 (NRG1) signaling, and is involved in neuronal migration and
      differentiation. Despite the potential significance of ERBB4 in the development
      of schizophrenia, relatively few genetic studies for the association of ERBB4
      with schizophrenia were performed in the populations including Ashkenazi Jews,
      Americans including Caucasians and African Americans, and Han Chinese. In this
      study, differences in ERBB4 variations were investigated to determine association
      with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean
      population. Seven polymorphisms in ERBB4 gene were genotyped in 435 schizophrenia
      cases and 390 unrelated healthy controls. In order to investigate the
      relationship between ERBB4 and the risk of schizophrenia and SPEM abnormality,
      differences in SNP and haplotype distribution were analyzed using logistic and
      multiple regression analyses. However, we failed to replicate the associations
      reported by previous studies in other populations. Although statistically not
      significant, the tendency towards associations between ERBB4 polymorphisms and
      the risk of schizophrenia and SPEM abnormality in this study from a Korean
      population would be helpful for further genetic etiology studies in
      schizophrenia.

PMID- 22634067
TI  - Citalopram alleviates chronic stress induced depression-like behaviors in rats by
      activating GSK3beta signaling in dorsal hippocampus.
AB  - Aside from monoamine disturbances, recent evidence has implicated particular
      intracellular pathways, including Wnt signaling, in the pathogenesis of major
      depressive disorder. In the present study, we investigated the role of Wingless
      (Wnt)-Dishevelled (DVL)-glycogen synthase kinase 3beta (GSK3beta) signaling in
      the depression-like behaviors exhibited by rats exposed to chronic forced swim
      stress. We found that the rats subjected to forced swim stress for 14 consecutive
      days exhibited obvious depression-like behaviors and showed decreased levels of
      phosphorylated GSK3beta and beta-catenin in the hippocampus. Chronic citalopram
      treatment alleviated the depression-like behaviors and reversed the disruptions
      of the phosphorylated GSK3beta and beta-catenin in stressed rats. Furthermore,
      when the stressed rats with citalopram treatment received bilateral, dorsal
      hippocampus infusions of a DVL inhibitor, sulindac, the depression-like effects
      induced by chronic stress reappeared. These findings suggest that the Wnt-DVL
      GSK3beta signaling in the hippocampus is markedly involved in the pathophysiology
      of depression induced by chronic stress. The Wnt-DVL-GSK3beta pathway may mediate
      the therapeutic action of citalopram, and the manipulation of DVL could be a
      target for novel antidepressants.

PMID- 22634068
TI  - Long-term follow-up of tibiocalcaneal arthrodesis in diabetic patients with early
      chronic Charcot osteoarthropathy.
AB  - Charcot osteoarthropathy with severe ankle instability and deformity is often
      managed with below-the-knee amputation if deformity and cutaneous compromise
      result in osteomyelitis. Recently, some surgeons have reported satisfactory
      outcomes with ankle arthrodesis in the coalescence or remodeling (subacute and
      chronic) stages of the disease before the onset of joint instability, severe
      deformity, and ulcer formation. This observational study describes the clinical
      outcomes of ankle arthrodesis in a cohort of 45 diabetic patients who underwent
      unilateral ankle arthrodesis for Charcot neuroarthropathic ankle deformity before
      the development of ulceration and bone infection. Two (4.44%) of the patients
      were lost to follow-up, whereas 2 (4.44%) others underwent below-the-knee
      amputation shortly after the ankle arthrodesis because of postoperative
      infection. After a mean follow-up duration of 5 +/- 2.85 years, 39 (86.67%)
      patients returned to independent ambulation wearing custom-made shoes with molded
      insoles, whereas 2 (4.44%) others required pneumatic casts for ambulation.

PMID- 22634070
TI  - Injectable system for spatio-temporally controlled delivery of hypoxia-induced
      angiogenic signalling.
AB  - While chronically ischaemic tissues are continuously exposed to hypoxia, the
      primary angiogenic stimulus, they fail to appropriately respond to it, as hypoxia
      regulated angiogenic factor production gradually undergoes down-regulation, thus
      hindering adaptive angiogenesis. We have previously reported on two strategies
      for delivering on demand hypoxia-induced signalling (HIS) in vivo, namely,
      implanting living or non-viable hypoxic cell-matrix depots that actively produce
      factors or act as carriers of factors trapped within the matrix during in vitro
      pre-conditioning, respectively. This study aims to improve this approach through
      the development of a novel, injectable system for delivering cell-free matrix HIS
      carriers. 3D spiral collagen constructs, comprising an inner cellular and outer
      acellular compartment, were cultured under hypoxia (5% O2). Cell-produced
      angiogenic factors (e.g. VEGF, FGF, PLGF, IL-8) were trapped within the nano
      porous matrix of the acellular compartment as they radially diffused through it.
      The acellular matrix was mechanically fragmented into micro-fractions and added
      into a low temperature (5  degrees C) thermo-responsive type I collagen solution,
      which underwent a collagen concentration-dependent solution-to-gel phase
      transition at 37  degrees C. Levels of VEGF and IL-8, delivered from matrix
      fractions into media by diffusion through collagen sol-gel, were up-regulated by
      day 4 of hypoxic culture, peaked at day 8, and gradually declined towards the
      baseline by day 20, while FGF levels were stable over this period. Factors
      captured within matrix fractions were bioactive after 3 months freeze storage, as
      shown by their ability to induce tubule formation in an in vitro angiogenesis
      assay. This system provides a minimally invasive, and repeatable, method for
      localised delivery of time-specific, cell-free HIS factor mixtures, as a tool for
      physiological induction of spatio-temporally controlled angiogenesis.

PMID- 22634071
TI  - Self-assembled glycol chitosan nanogels containing palmityl-acylated exendin-4
      peptide as a long-acting anti-diabetic inhalation system.
AB  - Inhalable deoxycholic acid-modified glycol chitosan (DOCA-GC) nanogels containing
      palmityl acylated exendin-4 (Ex4-C16) were prepared by self-assembly and
      characterized physicochemically. The lung deposition of DOCA-GC nanogels was
      monitored using an infrared imaging system, and the hypoglycemia caused by Ex4
      C16-loaded DOCA-GC nanogels was evaluated after pulmonary administration in type
      2 diabetic db/db mice. The cytotoxicities and lung histologies induced by DOCA-GC
      nanogels were examined in human lung epithelial cells (A549 and Calu-3) and db/db
      mice, respectively. Results showed that the DOCA-GC nanogels prepared were
      spherical and compact and had a diameter of ~220 nm. Although the incorporation
      of Ex4-C16 (50.9+/-7.8%) into DOCA-GC nanogels was significantly lower than that
      of Ex4 (81.4+/-4.9%), the Ex4-C16 release from DOCA-GC nanogels was greatly
      delayed vs. Ex4. DOCA-GC nanogels were deposited rapidly after pulmonary
      administration and remained in the lungs for ~72 h. Furthermore, the hypoglycemic
      duration of inhaled Ex4-C16 nanogels was much greater than that of Ex4 nanogels
      in db/db mice. Cytotoxicity results of DOCA-GC nanogels were considered
      acceptable, and the tissue histologies of mouse lungs administered nanogels did
      not show any significant difference vs. control lungs. The authors believe that
      Ex4-C16 DOCA-GC nanogels offer a long-acting inhalation delivery system for
      treating type 2 diabetes.

PMID- 22634072
TI  - The development and characteristics of novel microneedle arrays fabricated from
      hyaluronic acid, and their application in the transdermal delivery of insulin.
AB  - The aim of the present study was to develop novel insulin-loaded microneedle
      arrays (MNs) fabricated from hyaluronic acid (HA), and characterize their
      applicability in the transdermal delivery of insulin. The shape of MNs was
      observed via scanning electron microscopy. The characteristics of these novel
      insulin-loaded MNs, including hygroscopy, stability, drug release profiles, and
      dissolution properties, were evaluated from a clinical application point-of-view.
      Transepidermal water loss (TEWL) was measured to investigate the piercing
      properties of MNs, and the recovery of the skin barrier after the removal of MNs
      to confirm their safety. Additionally, the transdermal absorption of insulin from
      MNs was examined via an in vivo absorption study in diabetic rats. The length of
      MNs was 800 MUm with a base diameter of 160 MUm and a tip diameter of 40 MUm. MNs
      were found to maintain their skin piercing abilities for at least 1h, even at a
      relative humidity of 75%. After storing insulin-loaded MNs for a month at -40, 4,
      20, and 40  degrees C, more than 90% of insulin remained in MNs at all
      temperatures, indicating that insulin is highly stable in MNs at these storage
      conditions. It was also found that insulin is rapidly released from MNs via an in
      vitro release study. These findings were consistent with the complete dissolution
      of MNs within 1h of application to rat skin in vivo. Therefore, the novel HA MNs
      possess self-dissolving properties after their dermal application, and insulin
      appears to be rapidly released from these MNs. A significant increase in TEWL was
      observed after the application of MNs. However, this parameter recovered back to
      baseline within 24h after the removal of MNs. These findings indicate that the
      transdermal transport pathway of insulin, which was created by the MNs,
      disappeared within 24h, and that the skin damage induced by the MNs was
      reversible. Furthermore, a dose-dependent hypoglycemic effect and transdermal
      delivery of insulin were observed after a dermal treatment with insulin-loaded
      MNs in vivo. A continuous hypoglycemic effect was observed after 0.25 IU of
      insulin was administered to skin via MNs. Additionally, lower peak plasma insulin
      levels, but higher plasma insulin concentrations after 2 h, were achieved with
      0.25 IU of insulin administered via MNs as compared to the subcutaneous
      administration of insulin of the same dose. Pharmacodynamic and pharmacokinetic
      parameters indicated that insulin administered via MNs was almost completely
      absorbed from the skin into the systemic circulation, and that the hypoglycemic
      effect of insulin-loaded MNs was almost similar to that of the subcutaneous
      injection of insulin. These findings indicate that the novel insulin-loaded MNs
      fabricated from HA are a very useful alternative method of delivering insulin via
      the skin into the systemic circulation without inducing serious skin damage.
      Therefore, HA MNs may be an effective and safe method of transdermal insulin
      delivery in the clinic.

PMID- 22634069
TI  - Redox balance dynamically regulates vascular growth and remodeling.
AB  - Vascular growth and remodeling responses entail several complex biochemical,
      molecular, and cellular responses centered primarily on endothelial cell
      activation and function. Recent studies reveal that changes in endothelial cell
      redox status critically influence numerous cellular events that are important for
      vascular growth under different conditions. It has been known for some time that
      oxidative stress actively participates in many aspects of angiogenesis and
      vascular remodeling. Initial studies in this field were largely exploratory with
      minimal insight into specific molecular mechanisms and how these responses could
      be regulated. However, it is now clear that intracellular redox mechanisms
      involving hypoxia, NADPH oxidases (NOX), xanthine oxidase (XO), nitric oxide and
      its synthases, and intracellular antioxidant defense pathways collectively
      orchestrate a redox balance system whereby reactive oxygen and nitrogen species
      integrate cues controlling vascular growth and remodeling. In this review, we
      discuss key redox regulation pathways that are centrally important for vascular
      growth in tissue health and disease. Important unresolved questions and issues
      are also addressed that requires future investigation.

PMID- 22634074
TI  - Magnetic Active Agent Release System (MAARS): evaluation of a new way for a
      reproducible, externally controlled drug release into the small intestine.
AB  - Human absorption studies are used to test new drug candidates for their
      bioavailability in different regions of the gastrointestinal tract. In order to
      replace invasive techniques (e.g. oral or rectal intubation) a variety of
      externally controlled capsule-based drug release systems has been developed. Most
      of these use ionizing radiation, internal batteries, heating elements or even
      chemicals for the localization and disintegration process of the capsule. This
      embodies potential harms for volunteers and patients. We report about a novel
      technique called "Magnetic Active Agent Release System" (MAARS), which uses
      purely magnetic effects for this purpose. In our trial thirteen healthy
      volunteers underwent a complete monitoring and release procedure of 250 mg
      acetylsalicylic acid (ASA) targeting the flexura duodenojejunalis and the mid
      part of the jejunum. During all experiments MAARS initiated a sufficient drug
      release and was well tolerated. Beside this we also could show that the
      absorption of ASA is about two times faster in the more proximal region of the
      flexura duodenojejunalis with a tmax of 47+/-13 min compared to the more distal
      jejunum with tmax values of 100+/-10 min (p=0.031).

PMID- 22634073
TI  - A novel, biased-like SDF-1 derivative acts synergistically with starPEG-based
      heparin hydrogels and improves eEPC migration in vitro.
AB  - The CXC chemokine stromal cell-derived factor-1alpha (SDF-1alpha, CXCL12) has
      been proven to recruit CXCR4 positive stem and progenitor cells of different
      sources to defected heart sites, with significant clinical benefits. However, the
      rapid proteolytic inactivation by inflammation-related proteases, inaccurate drug
      delivery or inappropriate local concentrations belong to the largest
      disadvantages for feasible application. Herein, we present a switchable, biased
      like SDF-1alpha variant, AAV-[S4V]-SDF-1alpha, whose distinct activity is coupled
      to the inflammation-associated presence of dipeptidylpeptidase-4 (DPP-4), which
      cleaves an alanine-alanine dipeptide from the precursor. We decorated starPEG
      heparin hydrogels with our novel SDF-1alpha variant and tested them for
      immobilization efficiency, time-dependent protein release as well as mobilization
      of early endothelial progenitor cells (eEPCs) in vitro. We found higher migration
      rates compared to conventional SDF-1alpha. In summary, we provide a conceptual
      work on cooperative effects of enzymatically activatable SDF-1alpha and starPEG
      heparin hydrogels.

PMID- 22634075
TI  - Exercise intervention in childhood obesity: a randomized controlled trial
      comparing hospital-versus home-based groups.
AB  - OBJECTIVE: The aim of this study was to compare the effect of a hospital clinic
      group- versus home-based combined exercise-diet program for the treatment of
      childhood obesity. METHODS: One hundred ten overweight/obese Spanish children and
      adolescents (6-16 years) in 2 intervention groups (hospital clinic group-based [n
      = 45] and home-based [n = 41]) and a sex-age-matched control group (n = 24) were
      randomly assigned to participate in a 6-month combined exercise (aerobic and
      resistance training) and Mediterranean diet program. Anthropometric values
      (including body weight, height, body mass index, BMI-Z score, and waist
      circumference) were measured pre- and postintervention for all the participants.
      Percentage body fat was also determined with a body fat analyzer (TANITA TBF-410
      M). RESULTS: Our study showed a significant reduction in percentage body fat and
      body mass index Z-score among both intervention-group participants (4%, 0.16,
      hospital clinic group-based; 4.4%, 0.23, home-based; P < .0001). There was also a
      significant reduction in waist circumference in the home-based group (4.4 cm; P =
      .019). Attendance rates at intervention sessions were equivalent for both
      intervention groups (P = .805). CONCLUSIONS: The study findings indicate that a
      simple home-based combined exercise and Mediterranean diet program may be
      effective among overweight and obese children and adolescents, because it
      improves body composition, is feasible and can be adopted on a large scale
      without substantial expenses.

PMID- 22634076
TI  - Neonatal cholestasis: opportunities to increase early detection.
AB  - OBJECTIVE: To describe primary care management of early and prolonged jaundice in
      otherwise-healthy term infants to identify opportunities to increase early
      diagnosis of cholestasis. METHODS: Community-based pediatricians in St Louis,
      Missouri completed a mailed, anonymous, 29-item survey to assess practice
      demographics, timing of routine newborn office visits, and the management of
      early and prolonged neonatal jaundice. RESULTS: A total of 108 of 230 (47%) of
      eligible physicians responded (mean years in practice, 15.3, SD, 9.4). More
      respondents were very familiar with national guidelines for management of early
      (49%) than prolonged (16%) neonatal jaundice. Eighty-six percent reported all
      newborns were checked with transcutaneous bilirubin before hospital discharge.
      For transcutaneous bilirubin results at 48 hours of 7, 10, 12 and 15 mg/dL, 1%,
      26%, 70%, and 74% of respondents, respectively, would order a fractionated
      bilirubin. Although the first routine visit usually occurred in the first week
      after discharge, 25% of physicians reported the 2nd visit was routinely scheduled
      after 4 weeks of age. Ninety-four percent reported they would obtain a
      fractionated bilirubin for infants jaundiced beyond 4 weeks of age. If
      cholestasis was identified at 6 weeks of age, 32% would obtain additional testing
      without referral to a subspecialist. CONCLUSIONS: Management of early and
      prolonged neonatal jaundice is variable. Current practices appear to miss
      opportunities for early diagnosis of cholestasis and referral that are unlikely
      to be addressed without redesigning systems of care.

PMID- 22634078
TI  - Physicians who use social media and other internet-based communication
      technologies.
AB  - The demographic and practice-related characteristics of physicians who use social
      networking websites, portable devices to access the internet, email to
      communicate with patients, podcasts, widgets, RSS feeds, and blogging were
      investigated. Logistic regression was used to analyze a survey of US primary care
      physicians, pediatricians, obstetrician/gynecologists, and dermatologists
      (N=1750). Reported technology use during the last 6 months ranged from 80.6%
      using a portable device to access the internet to 12.9% writing a blog. The most
      consistent predictors of use were being male, being younger, and having teaching
      hospital privileges. Physician specialty, practice setting, years in practice,
      average number of patients treated per week, and number of physicians in practice
      were found to be inconsistently associated or unassociated with use of the
      technologies examined. Demographic characteristics, rather than practice-related
      characteristics, were more consistent predictors of physician use of seven
      internet-based communication technologies with varying levels of uptake.

PMID- 22634077
TI  - Improving clinician self-efficacy does not increase asthma guideline use by
      primary care clinicians.
AB  - OBJECTIVE: The purpose of this study was to show the association between changes
      in clinician self-efficacy and readiness to change and implementation of an
      asthma management program (Easy Breathing). METHODS: A 36 month randomized,
      controlled trial was conducted involving 24 pediatric practices (88 clinicians).
      Randomized clinicians received interventions designed to enhance clinician self
      efficacy and readiness to change which were measured at baseline and 3 years.
      Interventions consisted of an educational toolbox, seminars, teleconferences,
      mini-fellowships, opinion leader visits, clinician-specific feedback, and pay for
      performance. The primary outcome was program utilization (number of children
      enrolled in Easy Breathing/year); secondary outcomes included development of a
      written treatment plan and severity-appropriate therapy. RESULTS: At baseline,
      clinicians enrolled 149 +/- 147 (mean +/- SD) children/clinician/year; 84% of
      children had a written treatment plan and 77% of plans used severity-appropriate
      therapy. At baseline, higher self-efficacy scores were associated with greater
      program utilization (relative rate [RR], 1.34; 95% confidence interval [CI], 1.04
      1.72; P = .04) but not treatment plan development (RR, 0.63; 95% CI, 0.29-1.35; P
      = .23) or anti-inflammatory use (RR, 1.76; 95% CI, 0.92-3.35; P = .09).
      Intervention clinicians participated in 17 interventions over 36 months. At study
      end, self-efficacy scores increased in intervention clinicians compared to
      control clinicians (P = .01) and more clinicians were in an action stage of
      change (P = .001) but these changes were not associated with changes in primary
      or secondary outcomes. CONCLUSIONS: Self-efficacy scores correlated with program
      use at baseline and increased in the intervention arm, but these increases were
      not associated with greater program-related activities. Self-efficacy may be
      necessary but not sufficient for behavior change.

PMID- 22634079
TI  - Development of an AlphaLISA assay to quantify serum core-fucosylated E-cadherin
      as a metastatic lung adenocarcinoma biomarker.
AB  - Lung cancer is the leading cause of cancer-associated deaths worldwide. Non-small
      cell lung cancer is a heterogeneous condition with variability in prognosis and
      in individual response to treatment. Thus, the identification of patients with a
      high risk of metastasis or relapse after surgery would allow better management.
      There is increasing evidence that glycosylation plays a significant role in
      biological processes including oncogenic transformation and metastasis. We set up
      a platform to screen and identify serum glycoproteins as metastasis biomarkers of
      lung cancer. Concanavalin A affinity chromatography was used to enrich
      glycoproteins from pooled serum of lung adenocarcinoma patients. The captured
      glycoproteins were separated with 2-D DIGE combined with nano-LC-MS/MS and
      identified by database searching. Some differentially expressed cancer-related
      glycoproteins, such as alpha-1-antitrypsin, complement C3c, haptoglobin, and E
      cadherin, were identified. These glycoproteins were evaluated by Western blotting
      and Aleuria aurantia lectin staining and several, including E-cadherin, showed
      increased core-fucosylation during lung cancer progression. We then measured the
      fucosylation index (FI) of E-cadherin in 154 lung adenocarcinoma patients. In
      addition, a homogeneous proximity-based AlphaLISA assay to measure the FI of E
      cadherin was established. The present study indicates that the FI of E-cadherin
      could be a potential prognostic marker of metastatic lung adenocarcinoma.

PMID- 22634080
TI  - Internal calibrants allow high accuracy peptide matching between MALDI imaging MS
      and LC-MS/MS.
AB  - One of the important challenges for MALDI imaging mass spectrometry (MALDI-IMS)
      is the unambiguous identification of measured analytes. One way to do this is to
      match tryptic peptide MALDI-IMS m/z values with LC-MS/MS identified m/z values.
      Matching using current MALDI-TOF/TOF MS instruments is difficult due to the
      variability of in situ time-of-flight (TOF) m/z measurements. This variability is
      currently addressed using external calibration, which limits achievable mass
      accuracy for MALDI-IMS and makes it difficult to match these data to downstream
      LC-MS/MS results. To overcome this challenge, the work presented here details a
      method for internally calibrating data sets generated from tryptic peptide MALDI
      IMS on formalin-fixed paraffin-embedded sections of ovarian cancer. By
      calibrating all spectra to internal peak features the m/z error for matches made
      between MALDI-IMS m/z values and LC-MS/MS identified peptide m/z values was
      significantly reduced. This improvement was confirmed by follow up matching of LC
      MS/MS spectra to in situ MS/MS spectra from the same m/z peak features. The sum
      of the data presented here indicates that internal calibrants should be a
      standard component of tryptic peptide MALDI-IMS experiments.

PMID- 22634081
TI  - Label-free LC-MSMS analysis of vitreous from autoimmune uveitis reveals a
      significant decrease in secreted Wnt signalling inhibitors DKK3 and SFRP2.
AB  - Equine recurrent uveitis is a severe and frequent blinding disease in horses
      which presents with auto-reactive invading T-cells, resulting in the destruction
      of the inner eye. Infiltration of inflammatory cells into the retina and vitreous
      is driven by currently unknown guidance cues, however surgical removal of the
      vitreous (vitrectomy) has proven therapeutically successful. Therefore, proteomic
      analyses of vitrectomy samples are likely to result in detection of proteins
      contributing to disease pathogenesis. Vitreous from healthy and ERU diseased
      horses were directly compared by quantitative mass spectrometry based on label
      free quantification of peak intensities across samples. We found a significant
      upregulation of complement and coagulation cascades and downregulation of
      negative paracrine regulators of canonical Wnt signalling including the Wnt
      signalling inhibitors DKK3 and SFRP2. Based on immunohistochemistry, both
      proteins are expressed in equine retina and suggest localisation to retinal
      Muller glial cells (RMG), which may be the source cells for these proteins.
      Furthermore, retinal expression levels and patterns of DKK3 change in response to
      ERU. Since many other regulated proteins identified here are associated with RMG
      cells, these cells qualify as the prime responders to autoimmune triggers.

PMID- 22634082
TI  - Going forward: Increasing the accessibility of imaging mass spectrometry.
AB  - The driving force behind the high and increasing popularity of imaging mass
      spectrometry is its demonstrated potential for the determination of new
      diagnostic/prognostic biomarkers and its ability to simultaneously trace the
      distributions of pharmaceuticals and their metabolites in tissues without the
      need to develop expensive radioactively-labeled analogues. Both of these
      applications would benefit from standardized methods, for the development of
      novel MS-based molecular histology tests and governmental-approved MS-based
      assays for pharmaceutical development. In addition, the broader scientific
      community would benefit from the increased accessibility of the technique.
      Currently imaging MS studies are individual endeavors, utilizing the individual
      expertise and infrastructure of a single laboratory and their immediate
      collaborators. A wide array of tissue preparation, data acquisition and data
      analysis techniques has been developed but lacks an international collaborative
      structure and data sharing capabilities. Such a collaborative framework would
      enable methodological exchange and detailed comparisons of analytical
      capabilities, to explore synergies between the different methods and result in
      the development of robust standardized methods. Here we describe the activities
      of a new European imaging MS network that will explicitly compare and contrast
      existing methods to provide best practice guidelines for the entire healthcare
      research community.

PMID- 22634083
TI  - In-depth analysis of the human tear proteome.
AB  - The tears, a critical body fluid of the surface of the eye, contain an unknown
      number of molecules including proteins/peptides, lipids, small molecule
      metabolites, and electrolytes. There have been continued efforts for exploring
      the human tear proteome to develop biomarkers of disease. In this study, we used
      the high speed TripleTOF 5600 system as the platform to analyze the human tear
      proteome from healthy subjects (3 females and 1 male, average age: 36+/-14). We
      have identified 1543 proteins in the tears with less than 1% false discovery
      rate, which represents the largest number of human tear proteins reported to
      date. The data set was analyzed for gene ontology (GO) and compared with the
      human plasma proteome, NEIBank lacrimal gland gene dataset and NEIBank cornea
      gene dataset. This comprehensive tear protein list may serve as a reference list
      of human tear proteome for biomarker research of ocular diseases or establishment
      of MRM (Multiple Reaction Monitoring) assays for targeted analysis. Tear fluid is
      a useful and an accessible source not only for evaluating ocular surface tissues
      (cornea and conjunctiva), inflammation, lacrimal gland function and a number of
      disease conditions, such as dry eye as well as response to treatment.

PMID- 22634084
TI  - Analysis of N-glycosylation in maize cytokinin oxidase/dehydrogenase 1 using a
      manual microgradient chromatographic separation coupled offline to MALDI-TOF/TOF
      mass spectrometry.
AB  - Cytokinin oxidase/dehydrogenase (CKO; EC 1.5.99.12) irreversibly degrades the
      plant hormones cytokinins. A recombinant maize isoenzyme 1 (ZmCKO1) produced in
      the yeast Yarrowia lipolytica was subjected to enzymatic deglycosylation by
      endoglycosidase H. Spectrophotometric assays showed that both activity and
      thermostability of the enzyme decreased after the treatment at non-denaturing
      conditions indicating the biological importance of ZmCKO1 glycosylation. The
      released N-glycans were purified with graphitized carbon sorbent and analyzed by
      MALDI-TOF MS. The structure of the measured high-mannose type N-glycans was
      confirmed by tandem mass spectrometry (MS/MS) on a Q-TOF instrument with
      electrospray ionization. Further experiments were focused on direct analysis of
      sugar binding. Peptides and glycopeptides purified from tryptic digests of
      recombinant ZmCKO1 were separated by reversed-phase chromatography using a manual
      microgradient device; the latter were then subjected to offline-coupled analysis
      on a MALDI-TOF/TOF instrument. Glycopeptide sequencing by MALDI-TOF/TOF MS/MS
      demonstrated N-glycosylation at Asn52, 63, 134, 294, 323 and 338. The bound
      glycans contained 3-14 mannose residues. Interestingly, Asn134 was found only
      partially glycosylated. Asn338 was the sole site to carry large glycan chains
      exceeding 25 mannose residues. This observation demonstrates that contrary to a
      previous belief, the heterologous expression in Y. lipolytica may lead to locally
      hyperglycosylated proteins.

PMID- 22634085
TI  - Comprehensive profiling of proteome changes upon sequential deletion of
      deubiquitylating enzymes.
AB  - Deubiquitylating enzymes (DUBs) are a large group of proteases that regulate
      ubiquitin-dependent metabolic pathways by cleaving ubiquitin-protein bonds. Here
      we present a global study aimed at elucidating the effects DUBs have on protein
      abundance changes in eukaryotic cells. To this end we compare wild-type
      Saccharomyces cerevisiae to 20 DUB knock-out strains using quantitative
      proteomics to measure proteome-wide expression of isotope labeled proteins, and
      analyze the data in the context of known transcription-factor regulatory
      networks. Overall we find that protein abundances differ widely between
      individual deletion strains, demonstrating that removing just a single component
      from the complex ubiquitin system causes major changes in cellular protein
      expression. The outcome of our analysis confirms many of the known biological
      roles for characterized DUBs such as Ubp3p and Ubp8p, and we demonstrate that
      Sec28p is a novel Ubp3p substrate. In addition we find strong associations for
      several uncharacterized DUBs providing clues for their possible cellular roles.
      Hierarchical clustering of all deletion strains reveals pronounced similarities
      between various DUBs, which corroborate current DUB knowledge and uncover novel
      functional aspects for uncharacterized DUBs. Observations in our analysis support
      that DUBs induce both direct and indirect effects on protein abundances.

PMID- 22634086
TI  - Early storage lesions in apheresis platelets are induced by the activation of the
      integrin alphaIIbbeta3 and focal adhesion signaling pathways.
AB  - Production and storage of platelet concentrates (PC) induce protein changes in
      platelets leading to impaired platelet function. This study aimed to identify
      signaling pathways involved in the development of early platelet storage lesions
      in apheresis-PCs stored in plasma or additive solution (PAS). Apheresis-PCs from
      four donors were stored in plasma or in PAS at 22 degrees C (n=4 each). Platelets
      were analyzed at day 0 (production day) and after 1, 6 and 9 days of storage.
      Platelet response to agonists (TRAP, collagen, ADP) and to hypotonic shock
      decreased, CD62P expression increased in both storage media over time. Using DIGE
      1550 protein spots were monitored and compared to baseline values at day 0.
      Platelets in plasma displayed changes in 352 spots (166/day 1, 263/day 6 and
      201/day 9); in PAS 325 spots changed (202/day 1, 221/day 6, 200/day 9). LC-ESI
      MS/MS analysis of 405 platelet proteins revealed 32 proteins changed during
      storage in plasma (9/day 1, 15/day 6 and 26/day 9) and 28 in PAS (5/day 1, 20/day
      6, 26/day 9). Ingenuity pathway analysis found integrin-alphaII(b)beta(3) and
      focal adhesion signaling pathways involved in early alterations, being confirmed
      by Western blotting. Corresponding mRNAs in platelets were identified by next
      generation sequencing for 84 changed proteins. Integrin-alphaII(b)beta(3) and
      focal adhesion signaling cause irreversible early storage lesions in apheresis
      platelets. This article is part of a Special Issue entitled: Integrated omics.

PMID- 22634087
TI  - Detection and quantitation of forty eight cytokines, chemokines, growth factors
      and nine acute phase proteins in healthy human plasma, saliva and urine.
AB  - Cytokines, chemokines, growth factors (CCGFs) and other low abundance
      proteins/peptides in human body fluids or in tissues are potential biomarkers.
      Human body fluids such as plasma, saliva, urine, etc. are being analyzed more
      frequently than tissues primarily because of ease of sample collection. However,
      available information on concentrations of a large number of CCGFs in various
      body fluids of the same healthy individuals and gender-specific CCGFs is limited.
      In this work concentrations of 48 CCGFs were measured using multiplex bead assays
      and compared between plasma, saliva and urine collected from 20 male and female
      healthy volunteers. Forty three CCGFs were detected at least in one sample type
      of which 37 were in plasma, 41 were in saliva, and 34 were in urine; five CCGFs
      were not detected in any sample. Concentrations of detected CCGFs differed
      significantly between sample types but similar between gender groups. Gender
      specific CCGFs were also observed. Concentrations of nine acute phase proteins
      were also measured from plasma, saliva and urine to determine general health
      conditions of the volunteers. This work will provide an idea of which CCGFs are
      detectable and their relative concentrations in healthy human plasma, saliva and
      urine and which CCGFs are gender-specific.

PMID- 22634088
TI  - L27-tRNA interaction revealed by mutagenesis and pH titration.
AB  - The movement of peptidyl tRNA into the P-site after ribosome translocation
      reduces the ribosome dynamics in the post-translocation complex, which "locks"
      the ribosome to less conformational fluctuations. Here, we used single molecule
      FRET method to reveal that ribosomes bearing L27 with N-terminal truncations are
      less competent to "lock" the tRNA fluctuations after translocation. We found
      that: (1) truncation of the first three N-terminal residues of L27 increases
      peptidyl tRNA fluctuation; and (2) increasing the solution pH increases peptidyl
      tRNA fluctuation in WT and some of the ribosome mutants. We propose that one role
      of L27 at the catalytic center is to stabilize peptidyl tRNA in the post
      translocation complex.

PMID- 22634089
TI  - Roles and underlying mechanisms of ESAT-6 in the context of Mycobacterium
      tuberculosis-host interaction from a systems biology perspective.
AB  - The 6kDa early secreted antigenic target (ESAT-6), an important and intensively
      studied virulence factor of Mycobacterium tuberculosis, acts alone or in
      combination with CFP-10 to influence the outcome of the host-pathogen
      interaction. Secreted ESAT-6 can disturb the activation of macrophages, induce
      apoptosis and subvert host immunity. ESAT-6 mediated autophagosome formation and
      TLR signaling deviation lead to abnormal activation of NF-kappaB and subsequent
      erroneous expression of NF-kappaB-dependent genes. The C-terminal amino acid
      residues 90-95 in ESAT-6 are essential for the interaction with host. In-depth
      appreciation of the multiple roles of ESAT-6 upon host can inform improvements
      for novel vaccines and diagnostic tools for tuberculosis.

PMID- 22634090
TI  - Formulations based on alpha cyclodextrin and soybean oil: an approach to modulate
      the oral release of lipophilic drugs.
AB  - The purpose of this work was to investigate the potential of alpha-cyclodextrin
      combined to soybean oil-based formulations to modulate the release of a model
      drug, indomethacin. Dry emulsion, naked and coated beads were prepared from the
      same initial formulation using the same manufacturing process. Dry emulsion was
      selected to accelerate drug release while beads coated with alpha-cyclodextrin
      were designed to sustain it. Indomethacin-loaded systems were prepared,
      characterised and evaluated in vitro. Pharmacokinetic studies were performed in
      fasted and fed rats. The presence of the alpha-cyclodextrin coat was confirmed by
      confocal microscopy, and an increase of the mass and diameter of the beads. The
      layer of alpha-cyclodextrin improved their resistance in simulated gastro
      intestinal fluids. In vitro, the dissolution of indomethacin was slower with
      coated beads than with emulsion and naked beads. Lipid-based formulations showed
      an increase of relative bioavailability of IND versus Indocid(r). Whatever the
      formulation, greater and faster release of indomethacin was noticed in sodium
      taurocholate-rich medium and in fed rats. Compared to naked beads, an increased
      Cp(max) with a shorter T(max) was observed with the emulsion while T(max) and MRT
      were increased and Cp(max) reduced with the coated beads. Interestingly,
      formulations based on alpha cyclodextrin and soybean oil can modify the release
      of a lipophilic drug depending on the system formed.

PMID- 22634091
TI  - Development of a novel drug delivery system consisting of an antitumor agent
      tocopheryl succinate.
AB  - We have developed a novel drug delivery system (DDS) using an antitumor agent,
      alpha-tocopheryl succinate (TS). TS has attracted attention as a unique anti
      cancer drug for its ability to induce apoptosis in various cancer cells.
      Furthermore, TS itself readily forms nanovesicles (TS-NVs) and is a prospective
      tool for use as an antitumor DDS. However, TS-NVs are unstable for encapsulating
      drugs and passive targeting delivery to tumor tissue via enhanced permeation and
      retention effect. Therefore, to improve the stability of vesicles, we developed a
      novel nanovesicle consisting of TS and egg phosphatidylcholine (TS-EPC-NVs). The
      stability of vesicles of TS-EPC-NVs was significantly higher than that of TS-NVs.
      As a result, the in vivo antitumor activity of TS-EPC-NVs was more potent than
      that of TS-NVs. The enhanced antitumor activity of TS-EPC-NVs was found to be due
      to its effective intratumoral distribution. Moreover, the in vitro anticancer
      efficiency of TS-EPC-NVs increased seven-fold. We suggest that the improvement is
      due to homogenous cellular uptake and enhanced cytosolic delivery of the
      nanovesicles via alteration of intracellular trafficking. Furthermore, TS-EPC-NVs
      encapsulating siRNA showed significant knockdown efficiency. In summary, TS-EPC
      NVs represent a novel and attractive drug delivery system. The system shows
      antitumor activity of the encapsulated drug and the carrier itself.

PMID- 22634094
TI  - Prevalence and genetic variation of salivary gland hypertrophy virus in wild
      populations of the tsetse fly Glossina pallidipes from southern and eastern
      Africa.
AB  - The Glossina pallidipes salivary gland hypertrophy virus (GpSGHV) is a rod
      shaped, non-occluded double-stranded DNA virus that causes salivary gland
      hypertrophy (SGH) and reduced fecundity in the tsetse fly G. pallidipes. High
      GpSGHV prevalence (up to 80%) makes it impossible to mass-rear G. pallidipes
      colonies for the sterile insect technique (SIT). To evaluate the feasibility of
      molecular-based GpSGHV management strategies, we investigated the prevalence and
      genetic diversity of GpSGHV in wild populations of G. pallidipes collected from
      ten geographical locations in eastern and southern Africa. Virus diversity was
      examined using a total sequence of 1497 nucleotides (~ 1% of the GpSGHV genome)
      from five putative conserved ORFs, p74, pif1, pif2, pif3 and dnapol. Overall,
      34.08% of the analyzed flies (n=1972) tested positive by nested PCR. GpSGHV
      prevalence varied from 2% to 100% from one location to another but phylogenetic
      and gene genealogy analyses using concatenated sequences of the five putative
      ORFs revealed low virus diversity. Although no correlation of the virus diversity
      to geographical locations was detected, the GpSGHV haplotypes could be assigned
      to one of two distinct clades. The reference (Tororo) haplotype was the most
      widely distributed, and was shared by 47 individuals in seven of the 11
      locations. The Ethiopian haplotypes were restricted to one clade, and showed the
      highest divergence (with 14-16 single nucleotide mutation steps) from the
      reference haplotype. The current study suggests that the proposed molecular-based
      virus management strategies have a good prospect of working throughout eastern
      and southern Africa due to the low diversity of the GpSGHV strains.

PMID- 22634093
TI  - Drug-eluting microfibrous patches for the local delivery of rolipram in spinal
      cord repair.
AB  - Spinal cord injury (SCI) remains a major challenge for regenerative medicine.
      Following SCI, axon growth inhibitors and other inflammatory responses prevent
      functional recovery. Previous studies have demonstrated that rolipram, an anti
      inflammatory and cyclic adenosine monophosphate preserving small molecule,
      improves spinal cord regeneration when delivered systemically. However, more
      recent studies showed that rolipram has some adverse effects in spinal cord
      repair. Here, we developed a drug-delivery platform for the local delivery of
      rolipram into the spinal cord. The potential of drug-eluting microfibrous patches
      for continuous delivery of high and low-dose rolipram concentrations was
      characterized in vitro. Following C5 hemisections, athymic rats were treated with
      patches loaded with low and high doses of rolipram. In general, animals treated
      with low-dose rolipram experienced greater functional and anatomical recovery
      relative to all other groups. Outcomes from the high-dose rolipram treatment were
      similar to those with no treatment. In addition, high-dose treated animals
      experienced reduced survival rates suggesting that systemic toxicity was reached.
      With the ability to control the release of drug dosage locally within the spinal
      cord, drug-eluting microfibrous patches demonstrate the importance of appropriate
      local release-kinetics of rolipram, proving their usefulness as a therapeutic
      platform for the study and repair of SCI.

PMID- 22634092
TI  - Site-specific targeting of antibody activity in vivo mediated by disease
      associated proteases.
AB  - As a general strategy to selectively target antibody activity in vivo, a
      molecular architecture was designed to render binding activity dependent upon
      proteases in disease tissues. A protease-activated antibody (pro-antibody)
      targeting vascular cell adhesion molecule 1 (VCAM-1), a marker of atherosclerotic
      plaques, was constructed by tethering a binding site-masking peptide to the
      antibody via a matrix metalloprotease (MMP) susceptible linker. Pro-antibody
      activation in vitro by MMP-1 yielded a 200-fold increase in binding affinity and
      restored anti-VCAM-1 binding in tissue sections from ApoE-/- mice ex vivo. The
      pro-antibody was efficiently activated by native proteases in aorta tissue
      extracts from ApoE-/-, but not from normal mice, and accumulated in aortic
      plaques in vivo with enhanced selectivity when compared to the unmodified
      antibody. Pro-antibody accumulation in aortic plaques was MMP-dependent, and
      significantly inhibited by a broad-spectrum MMP inhibitor. These results
      demonstrate that the activity of disease-associated proteases can be exploited to
      site-specifically target antibody activity in vivo.

PMID- 22634096
TI  - WITHDRAWN: Geographic distribution of Wolbachia infection in mosquitoes from
      Thailand.
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- 22634095
TI  - Physiological performance of juvenile Haliotis rufescens and Haliotis discus
      hannai abalone exposed to the withering syndrome agent.
AB  - Withering syndrome (WS) is a serious chronic disease caused by infection with the
      bacterium Candidatus Xenohaliotis californiensis, a Rickettsiales-like organism
      (WS-RLO) that affects multiple abalone species in both natural and farmed
      populations. However, there is no available information regarding the effects of
      this disease on the physiological performance of infected abalone. We studied the
      effect of different levels of infection on components of energy balance and
      physiological indices (rates of absorption and assimilation, O/N ratio, and scope
      for growth) in the abalone species Haliotis rufescens and Haliotis discus hannai.
      Juveniles were exposed to C. X. californiensis transmission for 130 days, during
      which time the presence/absence of WS-RLOs was evaluated by PCR (following DNA
      sequencing-based confirmation of 100% identity with the sequence of C. X.
      californiensis from California), and the prevalence and intensity of infection
      were evaluated via histological analysis. Among H. rufescens juveniles exposed to
      the bacterium, 92% became infected (positive by histology), and the intensity of
      infection ranged from low (degree 1) to moderate (degree 2). In contrast, no H.
      discus hannai juveniles were positive for WS-RLO by histology, although 23% were
      positive by PCR, possibly indicating incipient WS-RLO infection that did not
      develop during the experimental period or to mere presence of WS-RLO DNA in the
      sample. Infection of H. rufescens juveniles by WS-RLOs negatively affected all
      components of the energy balance and physiological indices, such as scope for
      growth and the O/N ratio, in direct relation to the degree of infection. The most
      strongly affected functions were the rate of ingestion, standard metabolism, and
      production of feces, which were reduced by 60-80% in the most highly infected
      individuals. The reduced energy intake in the organisms produced a strong energy
      imbalance such that the energy available for growth was reduced by 49% in
      infected organisms. In contrast, juveniles of H. discus hannai carrying the
      bacterium developed no infection and showed no alterations of physiological
      function. Our results indicate that the level of early infection by WS-RLOs may
      exert a negative effect on physiological activity in H. rufescens, even when the
      disease is not evident.

PMID- 22634097
TI  - Role of the RAD51 G172T polymorphism in the clinical outcome of cervical cancer
      patients under concomitant chemoradiotherapy.
AB  - INTRODUCTION: Cervical cancer is one of the most common cancers diagnosed in
      women worldwide. Mammalian cells are constantly exposed to a wide variety of
      genotoxic agents from both endogenous and exogenous sources. The RAD51 protein is
      required for meiotic and mitotic recombination and plays a central role in
      homology-dependent recombinational repair of double-strand breaks (DSBs). Given
      the functional relevance of the DNA repair system on carcinogenesis, potential
      associations between genetic polymorphisms of DNA repair genes, cancer risk and
      response to therapy have been intensively evaluated. This is the first study
      evaluating the role of the RAD51 G172T genetic variants in cancer prognosis and
      clinical outcome of cervical cancer patients. MATERIAL AND METHODS: We analyzed
      RAD51 G172T polymorphism genotypes in cervical cancer patients who underwent a
      platinum-based chemotherapy in combination with radiotherapy. Genotyping was
      performed by TaqmanTM Allelic Discrimination methodology. RESULTS AND DISCUSSION:
      Concerning the overall survival rates found using Kaplan-Meier method and Log
      Rank Test, we observed that the mean survival rates were statistically different
      according to the patients RAD51 genotypes. The group of patients carrying the T
      allele present a higher mean survival rate than the other patients (102.3months
      vs. 86.4months, P=0.020). Using the Cox regression analysis, we found an
      increased overall survival time for T-carrier patients, when compared with GG
      genotype, with tumor stage, age and presence of lymph nodes as covariates [hazard
      ratio (HR), 0.373; 95% CI, 0.181-0.770; P=0.008]. Among patients (n=193), RAD51
      genotype frequency distributions were not under the influence of
      clinicopathologic characteristics, namely, treatment response (P=0.508),
      recurrence (P=0.150) and tumor stage (P=0.250). CONCLUSIONS: This is the first
      study evaluating the role of the RAD51 G172T genetic variants in cancer prognosis
      and clinical outcome of cervical cancer patients. Our results indicate an
      influence of the RAD51 genetic variants in overall survival of cervical cancer.
      Thereby, RAD51 G172T genotypes may provide additional prognostic information in
      cervical cancer patients who underwent cisplatin-based chemotherapy in
      combination with radiotherapy.

PMID- 22634098
TI  - Possible therapeutic effects of myxobacterial metabolites on type I Gaucher
      disease.
AB  - Gaucher disease (GD) is the most prevalent lysosomal storage disorder caused by
      an inherited deficiency of glucocerebrosidase. In the present study, we aimed to
      determine whether myxobacterial metabolites exhibit a potential therapeutic
      effect in the cells from a patient with type I GD. We screened 288 bioactive
      compounds of myxobacteria in the skin fibroblasts from a patient with type I GD.
      MTT assays were performed to determine their effects on cell viability. The
      expression levels of Bcl-2-associated X protein (Bax), ATP-citrate synthase (ATP
      CS), E3-binding protein (E3BP), and acetyl-coenzyme A acetyltransferase 1 (ACAT1)
      were determined by western blotting to understand the molecular mechanisms of
      myxobacterial metabolites in cells. Thin-layer chromatography (TLC) was carried
      out to measure changes in glucosylceramide levels in the cultured fibroblasts.
      This screening process identified 4 compounds that increased cell viability more
      than 1.45 times. After exposure to these compounds, the expression level of Bax
      decreased, whereas those of ATP-CS, E3BP, and ACAT1 increased. TLC revealed
      reduced amounts of intracellular glucosylceramides in patient cells. Here we
      suggest that myxobacterial metabolites can relieve the stress due to
      glucosylceramide accumulation, and that it may be utilized as a new therapeutic
      approach.

PMID- 22634099
TI  - PRNP gene variation in Pakistani cattle and buffaloes.
AB  - Bovine spongiform encephalopathy (BSE) is a neurodegenerative prion protein
      misfolding disorder of cattle. BSE is of two types, classical BSE and atypical
      BSE which in turn is of two types, H-type BSE and L-type BSE. Both H-type BSE and
      L-type BSE are primarily sporadic prion disorders. However, one case of H-type
      BSE has recently been associated with E211K polymorphism in the prion protein
      gene (PRNP). Two polymorphisms in the bovine PRNP are also associated with
      susceptibility to classical BSE: a 23 bp insertion/deletion (indel) in the PRNP
      promoter region and a 12 bp indel in the first intron. No information regarding
      BSE susceptibility in Pakistani cattle is available. The present study aimed at
      achieving this information. A total of 236 cattle from 7 breeds and 281 buffaloes
      from 5 breeds were screened for E211K polymorphism and 23 bp and 12 bp indels
      employing triplex PCR. The E211K polymorphism was not detected in any of the
      animals studied. The 23 bp insertion allele was underrepresented in studied
      cattle breeds while the 12 bp insertion allele was overrepresented. Both 23 bp
      and 12 bp insertion alleles were overrepresented in studied buffalo breeds.
      Almost 90% of alleles were insertion alleles across all studied buffalo breeds.
      The average frequency of 23 bp and 12 bp insertion alleles across all studied
      cattle breeds was found to be 0.1822 and 0.9407, respectively. There were
      significant differences between Pakistani and worldwide cattle in terms of
      allele, genotype and haplotype frequencies of 23 bp and 12 bp indels. The higher
      observed frequency of 12 bp insertion allele suggests that Pakistani cattle are
      relatively more resistant to classical BSE than European cattle. However, the key
      risk factor for classical BSE is the dietary exposure of cattle to contaminated
      feedstuffs.

PMID- 22634100
TI  - 335.4 kb microduplication in chromosome band Xp11.2p11.3 associated with
      developmental delay, growth retardation, autistic disorder and dysmorphic
      features.
AB  - About 10% of causative mutations for mental retardation in male patients involve
      X chromosome (X-linked mental retardation, XLMR). We describe a case of a 3-year
      old boy presenting with developmental delay, autistic features and growth and
      speech delay. Array-CGH analysis detected a microduplication on the X chromosome
      (Xp11.2p11.3), spanning 335.4 kb and including 3 known genes (ZNF81, ZNF182 and
      SPACA5). Genome-wide association studies show that approximately 30% of mutations
      causing XLMR are located in Xp11.2p11.3, where few pathogenic genes have been
      identified to date (such as ZNF41, PQB1 and ZNF81). ZNF81 codifies a zinc finger
      protein and mutations (non-sense mutations, deletions and structural
      rearrangements) involving this gene have already been described in association
      with mental retardation. Larger duplications in the same region have also been
      observed in association with mental retardation, and, in one case, the over
      expression of ZNF81 has also been verified by mRNA quantification. No
      duplications of the single gene have been identified. To our knowledge, the
      microduplication found in our patient is the smallest ever described in
      Xp11.2p11.3. This suggests that the over-expression of ZNF81 could have
      pathological effects.

PMID- 22634101
TI  - Genetic variation in DNA repair gene XRCC7 (G6721T) and susceptibility to breast
      cancer.
AB  - The human XRCC7 is a DNA double-strand break (DSBs) repair gene, involved in non
      homologous end joining (NHEJ). It is speculated that DNA DSBs repair have an
      important role during development of breast cancer. The human XRCC7 is a NHEJ
      DSBs repair gene. Genetic variation G6721T of XRCC7 (rs7003908) is located in the
      intron 8 of the gene. This polymorphism may regulate splicing and cause mRNA
      instability. In the present study, we specifically investigated whether common
      G6721T genetic variant of XRCC7 was associated with an altered risk of breast
      cancer. The present study included 362 females with breast cancer. Age frequency
      matched controls (362 persons) were randomly selected from the healthy female
      blood donors, according to the age distribution of the cases. Using RFLP-PCR
      based method, the polymorphism of XRCC7 was determined. The TG (OR=1.20, 95% CI:
      0.83-1.74, P=0.320) and TT (OR=1.01, 95% CI: 0.67-1.53, P=0.933) genotypes had no
      significant effect on risk of breast cancer, in comparison with the GG genotype.
      Our present findings indicate that the TT and TG genotypes were not associated
      with an altered breast cancer risk.

PMID- 22634102
TI  - Goat liver X receptor alpha, molecular cloning, functional characterization and
      regulating fatty acid synthesis in epithelial cells of goat mammary glands.
AB  - The liver X receptor alpha (LXRalpha) is a nuclear receptor of the transcription
      factor and is known to play a crucial role in lipid metabolism processes such as
      bile acid and fatty acid synthesis in humans and rodents. However, very little
      information is available on the role of LXRalpha in the regulation of fatty acid
      synthesis in the goat mammary gland. In this investigation, a cDNA was isolated
      from the mammary gland of Xinong Saanen dairy goats and designated as goat
      LXRalpha. RT-PCR and RACE gave rise to the full-length cDNA of LXRalpha, which
      was comprised of 1654 bp and characterized by an ORF of 1344 bp and 5'- and 3'
      UTR regions of 150 and 160 bp, respectively. The deduced amino acid sequence
      encodes 477 amino acids with a predicted molecular weight (MW) of 50.4kDa and a
      theoretical isoelectric point (pI) of 6.3. Additionally, homology search and
      sequence multi-alignment indicated that the putative goat LXRalpha amino acid
      sequence is very similar to those of cattle, mice, rats, swine, and humans.
      Bioinformatic predictions demonstrated that the LXRalpha protein is located in
      the nucleus, containing characteristic signatures of a nuclear receptor with DNA
      binding domain (DBD) and ligand-binding domain (LBD). Real-time quantitative PCR
      suggested that LXRalpha was predominantly expressed in the small intestine,
      liver, spleen and mammary gland. Treatment of goat mammary gland epithelial cells
      (GMEC) with different concentrations (i.e., 0.01, 0.1, 1 MUM) of T0901317, a
      synthetic agonist of LXRalpha, resulted in elevated sterol regulatory element
      binding protein 1 (SREBP1) and fatty acid synthase (FASN) mRNA levels in response
      to LXRalpha activation. The association between different T0901317 concentrations
      and fatty acid composition in GMEC also was examined using gas chromatography
      (GC). The results showed that activation of LXRalpha significantly increased GMEC
      C18:1 and C18:2 contents, but did not affect levels of saturated fatty acids
      (SFA). These discoveries are consistent with the notion that LXRalpha plays a key
      role in controlling lipogenesis and regulating synthesis of unsaturated fatty
      acids (UFA) in the mammary gland of goats, which may prove useful in regulation
      of milk fat production.

PMID- 22634103
TI  - Genome-wide identification and expression analysis of heat-responsive and novel
      microRNAs in Populus tomentosa.
AB  - Plant microRNAs have a vital role in various abiotic stress responses by
      regulating gene expression. Heat stress is one of the most severe abiotic
      stresses, and affects plant growth and development, even leading to death. To
      identify heat-responsive miRNAs at the genome-wide level in Populus, Solexa
      sequencing was employed to sequence two libraries from Populus tomentosa, treated
      and untreated by heat stress. Sequence analysis identified 134 conserved miRNAs
      belonging to 30 miRNA families, and 16 novel miRNAs belonging to 14 families.
      Among these miRNAs, 52 miRNAs from 15 families were responsive to heat stress and
      most of them were down-regulated. qRT-PCR analysis confirmed that the conserved
      and novel miRNAs were expressed in P. tomentosa, and revealed similar expression
      trends to the Solexa sequencing results obtained under heat stress. One hundred
      and nine targets of the novel miRNAs were predicted. This study opens up a new
      avenue for understanding the regulatory mechanisms of miRNAs involvement in the
      heat stress response of trees.

PMID- 22634104
TI  - Overexpression of a wheat MYB transcription factor gene, TaMYB56-B, enhances
      tolerances to freezing and salt stresses in transgenic Arabidopsis.
AB  - The MYB proteins play central roles in the stress response in plants. Our
      previous works identified a cold stress-related gene, TaMYB56, which encodes a
      MYB protein in wheat. In this study, we isolated the sequences of TaMYB56 genes,
      and mapped them to the wheat chromosomes 3B and 3D. The expression levels of
      TaMYB56-B and TaMYB56-D were strongly induced by cold stress, but slightly
      induced by salt stress in wheat. The detailed characterization of the Arabidopsis
      transgenic plants that overexpress TaMYB56-B revealed that TaMYB56-B is possibly
      involved in the responses of plant to freezing and salt stresses. The expression
      of some cold stress-responsive genes, such as DREB1A/CBF3 and COR15a, were found
      to be elevated in the TaMYB56-B-overexpressing Arabidopsis plants compared to
      wild-type. These results indicate that TaMYB56-B may act as a regulator in plant
      stress response.

PMID- 22634105
TI  - A mutagenesis-based screen to rapidly identify phosphorylation sites in mitogen
      activated protein kinase substrates.
AB  - Identification and characterization of protein phosphorylation sites often
      requires mass spectrometric analysis, which is not trivial or accessible to many
      laboratories. Here, a targeted strategy to mutagenize putative phosphorylation
      sites within mitogen-activated protein kinase (MAPK) substrates is described.
      This employs a combination of standard type II with type IIs restriction enzymes
      to rapidly create individual or multiple phosphorylation site mutant versions of
      kinase substrates with high efficiency, thereby reducing the cost for screening
      mutated clones.

PMID- 22634106
TI  - Online immobilized enzyme microreactor for the glucose oxidase enzymolysis and
      enzyme inhibition assay.
AB  - An online immobilized glucose oxidase (GOx) capillary microreactor was developed
      based on an enzymatic redox reaction with 1,4-benzoquinone as an acceptor of
      electrons, replacing the molecular oxygen typically used in a GOx reaction to
      achieve direct ultraviolet detection without derivation. A high efficiency of
      enzymolysis was obtained at 1 mg ml-1 1,4-benzoquinone for 5 min of incubation at
      25 degrees C, and baseline separation of the substrate and product could be
      achieved with a resolution of 3.85 by employing 20mM phosphate buffer (pH 8.0)
      containing 40 mg ml-1 sulfated beta-cyclodextrin as an additive, a constant
      voltage of 15 kV, and a detection wavelength of 220 nm. In addition, an online
      enzyme inhibition study was performed on the immobilized GOx microreactor with
      metal ions Ag+ and Cu2+ used as model inhibitors. The results indicate that Ag+
      (IC50=69.16 MUM) has a markedly higher inhibitory effect than Cu2+ (IC50=1.33
      mM). The protocol described can be applied in high-throughput screening of enzyme
      reactions and inhibitors.

PMID- 22634108
TI  - Preoperative serum levels of matrix metalloproteinase-2 (MMP-2) and survival of
      breast cancer among Korean women.
AB  - BACKGROUND: Matrix metalloproteinase-2 (MMP-2) has been thought of as a predictor
      of recurrence or metastasis risk or prognostic markers in cancer. We evaluated
      whether preoperative serum levels of MMP-2 work as a prognostic biomarker in
      breast cancer prognosis. METHODS: Preoperative serum levels of MMP-2 were
      measured with ELISA in 303 patients with histologically confirmed breast cancer.
      The median follow-up time for all patients was 4.24 years. The relationship of
      MMP-2 to survival was investigated using Cox proportional hazard regression model
      adjusted for the tumor-node-metastasis (TNM) stage and estrogen receptor (ER)
      status. RESULTS: In the multivariate analysis, disease-free survival (DFS) was
      worse among patients with the third tertile of MMP-2 level than with the first
      tertile of MMP-2 level [hazard ratio, 1.80; 95% confidence interval (CI), 1.04
      3.11; P = 0.04]. However, when the patients were stratified by age, ER status,
      histologic grade, and nuclear grade, inverse correlation was shown between serum
      MMP-2 levels and prognostic factors, and the associations between MMP-2 and DFS
      were only significant among patients with poor prognostic factors (HR, 2.75; 95%
      CI, 1.32-5.73 in ER-negative; HR, 2.90; 95% CI, 1.42-5.92 in histologic grade
      III; and HR, 2.61; 95% CI, 1.26-5.39 in nuclear grade III). CONCLUSIONS: Our
      results suggest that the preoperative serum levels of MMP-2 were associated with
      the survival in patients with breast cancer in ER-negative, higher histologic
      grade, or higher nuclear grade breast cancers. IMPACT: Our results indicate that
      serum levels of MMP-2 may play a role as prognostic biomarker in breast cancer
      survival.

PMID- 22634109
TI  - Fulminant necrotizing amoebic colitis.
AB  - The emergence of amoebiasis is of great public health concern since it has the
      potential to become endemic in developed nations essentially due to increased
      travel to endemic areas, emigration of people from affected nations and increase
      in the HIV-AIDS population. Fulminant necrotizing amoebic colitis is a rare and
      relatively less-known form of amoebiasis typically associated with very high
      morbidity and mortality, as is presented in the current case.

PMID- 22634107
TI  - Depressive symptoms enhance stress-induced inflammatory responses.
AB  - Depression is a risk factor for morbidity and mortality, and immune dysregulation
      may be partially responsible for this link. Proinflammatory cytokines such as
      interleukin 6 (IL-6) are reliable predictors of quality of life, morbidity, and
      many causes of mortality. The current study evaluated relationships between
      depressive symptoms, as assessed by the CES-D, and stress-induced inflammation.
      The participants, 138 healthy adults, were evaluated at rest, and after a
      standardized laboratory speech and mental arithmetic stressor. Compared with
      individuals with fewer depressive symptoms, those with more depressive symptoms
      produced more IL-6 in response to the stressor, as well as significantly higher
      levels of IL-6 both 45 min and 2 h after the stressor. These findings add to our
      emerging understanding of the complex interactions among stress, depression, and
      immune dysregulation, and provide one potential pathway to explain relationships
      between depressive symptoms and disease.

PMID- 22634110
TI  - Associations of physical activity with neighborhood environments and
      transportation modes in older Japanese adults.
AB  - OBJECTIVE: We investigated associations of walking and other leisure-time
      physical activity (LTPA) with environmental characteristics and transportation
      modes in older Japanese adults. METHODS: This cross-sectional study in 2010-2011
      used data from 421 community-dwelling older adults aged 65-85 years living in
      Kasama City, rural Japan. We used the Physical Activity Scale for the Elderly to
      assess walking and other LTPAs, and the International Physical Activity
      Questionnaire Environment Module for neighborhood environments. RESULTS: After
      adjusting for confounders, we found that good traffic safety and aesthetics were
      positively associated with high levels of walking (ORs=1.64-2.12); whereas, good
      access to public transportation was negatively associated with walking (OR=0.64,
      95% CI=0.42-0.98). Good access to recreational facilities, presence of sidewalks,
      absence of hills, seeing people exercise, and aesthetically pleasing surroundings
      were positively associated with high levels of LTPA except walking (ORs=1.61
      2.13). Individuals who rode bicycles more than once per week were more likely to
      engage in a LTPA except walking (1-3 days: OR=1.72, 95% CI=1.03-2.87; >=4 days:
      OR=2.90, 95% CI=1.71-4.93). CONCLUSION: This study adds information on correlates
      of physical activity among older Japanese adults; the positive association
      between LTPA except walking and the frequency of bicycle travel is an especially
      new and intriguing finding.

PMID- 22634111
TI  - Effects of Spent Pot Liner on mitotic activity and nuclear DNA content in
      meristematic cells of Allium cepa.
AB  - Industrial waste usually contains complex mixtures of mutagenic chemicals. Spent
      Pot Liner (SPL) is a complex solid waste from the aluminum industry, which is
      composed of organics, fluoride salts, inorganic cyanides, metals, and sodium. Due
      to the toxicity of these compounds, this study sought to use cytogenetics and
      flow cytometry to assess the effects of SPL on cell cycle parameters and DNA
      content in meristematic cells of Allium cepa. Three concentrations of leachates
      from SPL-soil mixtures were used for the study: 0, 10, and 25%. Roots were
      collected and analyzed after 4, 8, 12, 24, and 36 h of exposure to the above SPL
      leachates. The results showed an overall mitodepressive effect accompanied by an
      increased percentage of condensed nuclei and genomic instability as evidenced by
      the presence of cellular/chromosomal abnormalities. Terminal deoxynucleotidyl
      transferase dUTP nick end labeling revealed nuclei with fragmented DNA, a marker
      of programmed cell death. This study also addressed the question of reversibility
      of the effects of SPL and found that 36 h of exposure to 25% SPL seemed to be the
      point at which the effects on the induction of apoptosis became irreversible.

PMID- 22634113
TI  - Comment on the British Society of Gastroenterology guidelines for management of
      autoimmune hepatitis (part 1).
AB  - The British Society of Gastroenterology guidelines for management of autoimmune
      hepatitis were recently published in Gut. The chapters concerning epidemiology,
      presentation and diagnosis are addressed here.

PMID- 22634114
TI  - Effect of thermal injury on embryos of banded coral shrimp (Stenopus hispidus)
      under hypothermal conditions.
AB  - Cryopreservation technology regarding banded coral shrimp (Stenopus hispidus)
      embryos is important as it could improve cultivation and preservation of the
      species. The development of this technology is to reduce collections of this
      species from the wild, thus preventing damage to coral reefs. This study
      investigated the tolerance of different developmental stages of S. hispidus
      embryos in response to low temperature in the presence or absence of
      cryoprotectant. Embryos undergoing three stages of embryonic development (eye
      formation, heart beat and pre-hatch stage) were selected and exposed to 5, 0 and 
      5 degrees C in cryoprotectant solutions of 1 or 2M methanol for 1, 2, 4, 6, 8, 16
      and 32h. Embryo survival was evaluated based on their hatching percentage. In
      experiments on the effect of different concentrations of methanol on chilling
      sensitivity of embryos, it was determined that methanol at 1M methanol reduced
      the chilling sensitivities of embryos most effectively when compared to the other
      tested concentrations. Experiments regarding the chilling sensitivity of embryos
      in different developmental stages indicated that pre-hatch stage embryos were
      more resistant to subzero temperatures than early stage embryos; they tolerated
      the 32h exposure at 5 and 0 degrees C without a loss in survival. The study also
      indicated that late stage embryos are considered to be resistant to chilling, and
      that pre-late stage embryos are better candidate for cryopreservation.

PMID- 22634112
TI  - cAMP regulation of airway smooth muscle function.
AB  - Agonists activating beta(2)-adrenoceptors (beta(2)ARs) on airway smooth muscle
      (ASM) are the drug of choice for rescue from acute bronchoconstriction in
      patients with both asthma and chronic obstructive pulmonary disease (COPD).
      Moreover, the use of long-acting beta-agonists combined with inhaled
      corticosteroids constitutes an important maintenance therapy for these diseases.
      beta-Agonists are effective bronchodilators due primarily to their ability to
      antagonize ASM contraction. The presumed cellular mechanism of action involves
      the generation of intracellular cAMP, which in turn can activate the effector
      molecules cAMP-dependent protein kinase (PKA) and Epac. Other agents such as
      prostaglandin E(2) and phosphodiesterase inhibitors that also increase
      intracellular cAMP levels in ASM, can also antagonize ASM contraction, and
      inhibit other ASM functions including proliferation and migration. Therefore,
      beta(2)ARs and cAMP are key players in combating the pathophysiology of airway
      narrowing and remodeling. However, limitations of beta-agonist therapy due to
      drug tachyphylaxis related to beta(2)AR desensitization, and recent findings
      regarding the manner in which beta(2)ARs and cAMP signal, have raised new and
      interesting questions about these well-studied molecules. In this review we
      discuss current concepts regarding beta(2)ARs and cAMP in the regulation of ASM
      cell functions and their therapeutic roles in asthma and COPD.

PMID- 22634115
TI  - The effects of different sugars on motility, morphology and DNA damage during the
      liquid storage of rat epididymal sperm at 4 degrees C.
AB  - This study evaluated the protective effects of supplementation with three
      different sugars on the motility, morphology and DNA integrity of rat epididymal
      sperm chilled and stored at 4 degrees C Epididymides were obtained from each
      donor. Rat epididymal sperm was diluted in Ham's F10 plus raffinose, Ham's F10
      plus trehalose, Ham's F10 plus fructose, and Ham's F10 medium for control
      purposes. Thereafter, the extended sperm were chilled and stored in liquid form
      at 4 degrees C. Sperm motility, morphological abnormalities and DNA damage were
      determined at 0 and 12h after chilling. No significant difference was observed in
      any of the parameters evaluated at 0h, before storage (P>0.05). After 12h of
      storage, all sugar additives led to statistically higher motility, normal sperm
      morphology and DNA integrity in comparison to the control group. Raffinose gave
      the best motility percentages (32.86+/-1.84%) after 12h of storage at 4 degrees
      C, compared to the other groups (P<0.001). In conclusion, Raffinose, trehalose
      and fructose provided a better protection of sperm functional parameters against
      chilling injury, in comparison to the control group.

PMID- 22634116
TI  - Prevalence of adverse intraoperative events during obesity surgery and their
      sequelae.
AB  - BACKGROUND: Adverse intraoperative events (AIEs) during surgery are a well-known
      entity. A better understanding of the incidence of AIEs and their relationship
      with outcomes is helpful for surgeon preparation and preoperative patient
      counseling. The goals of this study are to describe the incidence of AIEs during
      bariatric surgery and examine their impact on major adverse complications. STUDY
      DESIGN: The study included 5,882 subjects who had bariatric surgery in the
      Longitudinal Assessment of Bariatric Surgery study between March 2005 and April
      2009. Prospectively collected AIEs included organ injuries, anesthesia-related
      events, anastomotic revisions, and equipment failure. The relationship between
      AIEs and a composite end point of 30-day major adverse complications (ie, death,
      venous thromboembolism, percutaneous, endoscopic, or operative reintervention and
      failure to be discharged from the hospital within 30 days from surgery) was
      evaluated using a multivariable relative risk model adjusting for factors known
      to influence their risk. RESULTS: There were 1,608 laparoscopic adjusted gastric
      banding, 3,770 laparoscopic Roux-en-Y gastric bypass operations, and 504 open
      Roux-en-Y gastric bypass operations. Adverse intraoperative events occurred in 5%
      of the overall sample and were most frequent during open Roux-en-Y gastric bypass
      (7.3%), followed by laparoscopic Roux-en-Y gastric bypass (5.5%) and laparoscopic
      adjusted gastric banding (3%). The rate of composite end point was 8.8% in the
      AIE group compared with 3.9% among those without an AIE (p < 0.001).
      Multivariable analysis revealed that patients with an AIE were at 90% greater
      risk of composite complication than those without an event (relative risk = 1.90;
      95% CI, 1.26-2.88; p = 0.002), independent of the type of procedure (open or
      laparoscopic). CONCLUSIONS: Incidence of an AIE is not infrequent during
      bariatric surgery and is associated with much higher risk of major complication.
      Additional study is needed to assess the association between specific AIEs and
      short-term complications.

PMID- 22634117
TI  - Outcomes of repeat cytoreductive surgery with hyperthermic intraperitoneal
      chemotherapy for the treatment of peritoneal surface malignancy.
AB  - BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal
      chemotherapy (HIPEC) has improved the survival of patients with peritoneal
      surface malignancy. On recurrence, a repeat CRS/HIPEC is a treatment option.
      STUDY DESIGN: A retrospective analysis of 868 CRS/HIPEC procedures was performed.
      Type of primary, functional status, completion of resection, hospitalization,
      morbidity, mortality, and survival were reviewed. RESULTS: Sixty-two patients
      (7.7%) underwent a second CRS/HIPEC, including 33 patients with appendiceal
      primaries, 8 ovarian, 7 mesotheliomas, 4 colon cancers, and 10 various
      malignancies. Median follow-up was 60.8 months. Median overall survival in months
      was 85.3 for appendiceal cancer, 52.9 for mesothelioma, 60.1 for ovarian, and
      137.4 for colon cancer. R1 resection was achieved in 43.5% after both procedures.
      Median survival after the second cytoreduction was 52.1 months for appendiceal
      cancer, 21.8 for mesothelioma, 53.9 for ovarian, and 55.7 for colon cancer.
      Median survival was 55.7 months for R1 resection, 20.3 months for R2a resection,
      and 15.5 months for R2b-R2c. Median ICU and hospital stay was 1 and 7.5 days,
      respectively. The 30-day morbidity after the second CRS/HIPEC was 48.4% and
      mortality was 3.2%. In multivariate analysis, the R status of the second
      CRS/HIPEC (p = 0.013) and the interval between the 2 procedures (p = 0.009) were
      significant in predicting improved survival. CONCLUSIONS: In experienced tertiary
      centers and for selected patients, a repeat CRS/HIPEC procedure has morbidity and
      mortality similar to the initial cytoreduction. Survival depends primarily on the
      completion of the repeat cytoreduction and favorable biology of the tumor.

PMID- 22634118
TI  - O' surgery case log data, where art thou?
AB  - BACKGROUND: The American College of Surgeons (ACS) Case Log represents a data
      system that satisfies the American Board of Surgery (ABS) Maintenance of
      Certification (MOC) program, yet has broad data fields for surgical
      subspecialties. Using the ACS Case Log, we have developed a method of data
      capture, categorization, and reporting of acute care surgery fellows'
      experiences. STUDY DESIGN: In July 2010, our acute care surgery fellowship
      required our fellows to log their clinical experiences into the ACS Case Log.
      Cases were entered similar to billable documentation rules. Keywords were entered
      that specified institutional services and/or resuscitation types. These data were
      exported in comma separated value format, deidentified, structured by Current
      Procedural Terminology (CPT) codes relevant to acute care surgery, and
      substratified by fellow and/or fellow year. RESULTS: Fifteen report types were
      created consisting of operative experience by service, procedure by major
      category (cardiothoracic, vascular, solid organ, abdominal wall, hollow viscus,
      and soft tissue), total resuscitations, ultrasound, airway, ICU services, basic
      neurosurgery, and basic orthopaedics. Results are viewable via a secure Web
      application, accessible nationally, and exportable to many formats. CONCLUSIONS:
      Using the ACS Case Log satisfies the ABS MOC program requirements and provides a
      method for monitoring and reporting acute care surgery fellow experiences. This
      system is flexible to accommodate the needs of surgical subspecialties and their
      training programs. As documentation requirements expand, efficient clinical
      documentation is a must for the busy surgeon. Although, our data entry and
      processing method has the immediate capacity for acute care surgery fellowships
      nationwide, multiple larger decisions regarding national case log systems should
      be encouraged.

PMID- 22634119
TI  - Liver resection for hepatocellular carcinoma <=3 cm: results of an Italian
      multicenter study on 588 patients.
AB  - BACKGROUND: The best treatment for patients with small hepatocellular carcinoma
      (S-HCC) is still controversial. The aim of this study was to evaluate operative
      and long-term results after liver resection (LR) for S-HCC, defined as tumor <=3
      cm. STUDY DESIGN: Retrospective multicenter study of 588 LRs for S-HCC from 8
      Italian hepatobiliary surgery units (years 1992 to 2008). Primary outcomes
      included operative risk. Logistic regression analysis was used to evaluate risk
      factors for postoperative mortality. Secondary outcomes were overall survival
      (OS) and disease-free survival (DFS), estimated by the Kaplan-Meier method.
      RESULTS: Postoperative mortality was 1.9%, morbidity was 35.7% (major morbidity
      7.3%), and blood transfusion rate was 13.8%. Child-Pugh class B and blood
      transfusions were associated with higher postoperative mortality. Rates of
      microvascular invasion and microsatellite nodules were 37.0% and 23.1%. After a
      median follow-up of 38.4 months, 5- and 10-year OS rates were 52.8% and 20.3%,
      with DFS of 32.4% and 21.7%. Local recurrence rate was 1.4%. Between the years
      2000 and 2008, 5-year OS was significantly higher than that between the years
      1992 and 1999 (61.9% vs 42.6%; p < 0.001). In multivariable analysis, Child-Pugh
      class B, portal hypertension, and microsatellite lesions were independently
      associated with poor OS. Microsatellite lesion was the only variable
      independently associated with poor DFS. CONCLUSIONS: Liver resection for S-HCC
      has improved over the years, with decreased operative risk. Long-term survival
      after LR has increased. Despite small tumor size, rates of microsatellite nodules
      and microvascular invasion are not negligible. Presence of microsatellite lesions
      was the only variable identified as being associated with poor both OS and DFS.

PMID- 22634120
TI  - Outcomes of endoscopic and percutaneous drainage of pancreatic fluid collections
      arising after pancreatic tail resection.
AB  - BACKGROUND: Up to 15% to 30% of patients develop pancreatic fluid collections
      (PFCs) after pancreatic tail resection. Percutaneous and endoscopic methods have
      been used to drain these collections, though few data are available that compare
      outcomes of these modalities. STUDY DESIGN: From December 1998 to April 2011, we
      identified all patients who underwent pancreatic tail resection and developed
      PFCs requiring intervention. The primary aim was to compare overall success rates
      in resolution of PFCs using endoscopic and percutaneous modalities. Success
      rates, hospital length of stay, number of CT scans, sinograms and endoscopies
      performed, and days with drain(s) in place were compared. RESULTS: Forty-eight
      patients were identified. Percutaneous drainage was performed a median of 25 days
      postoperatively, compared with 85 days for endoscopic drainage (p < 0.001).
      Endoscopic and percutaneous methods had similar rates of technical success (100%
      vs 97%, p = 0.50) and treatment success (80% vs 81%, p = 0.92), respectively.
      Recurrence rates were 16.6% for the endoscopic group and 23% for the percutaneous
      group (p = 0.65), and adverse events occurred in 9.4% of those treated
      endoscopically vs 13.3% of those treated percutaneously (p = 0.68). Location and
      characteristics of PFCs did not influence success rates. Recurrences were often
      treated by "salvage" drainage via the other modality. Median hospital stay was
      longer after primary percutaneous drainage compared with primary endoscopic
      drainage (5.5 days vs 2 days, p = 0.046). Primary percutaneous drainage patients
      also had more CT scans (median 3 vs 2, p = 0.03). CONCLUSIONS: Endoscopic
      drainage and percutaneous drainage appear to be equally effective and
      complementary interventions for PFCs occurring after pancreatic tail resection.
      Primary endoscopic drainage may be associated with shorter hospital stay and
      fewer CT scans.

PMID- 22634121
TI  - D-livering the message: the importance of vitamin D status in chronic liver
      disease.
AB  - Vitamin D is synthesized predominantly in the liver and functions as an important
      secosteroid hormone with pleiotropic effects. While its key regulatory role in
      calcium and bone homeostasis is well established, recently there is increasing
      recognition that vitamin D also regulates cell proliferation and differentiation,
      and has immunomodulatory, anti-inflammatory and anti-fibrotic properties. These
      non-skeletal effects are relevant in the pathogenesis and treatment of many
      causes of chronic liver disease. Vitamin D deficiency is frequently present in
      chronic liver disease and may predict non-response to antiviral therapy in
      chronic hepatitis C. Small studies suggest that vitamin D supplementation
      improves sustained viral response rates, while 1alpha-hydroxylase polymorphisms
      and vitamin D-binding protein are also implicated in therapeutic outcomes.
      Vitamin D deficiency also closely relates to the severity of non-alcoholic fatty
      liver disease (NAFLD) and is implicated in the pathogenesis of insulin
      resistance, a key factor in the development of NAFLD. In preclinical studies,
      phototherapy and vitamin D supplementation ameliorate NAFLD histopathology, while
      vitamin D is a powerful anti-fibrotic against thioacetamide liver injury. In
      liver transplant recipients severe vitamin D deficiency predicts, and vitamin D
      supplementation prevents, acute cellular rejection. The role of vitamin D in the
      activation and regulation of both innate and adaptive immune systems may explain
      its importance in the above liver diseases. Further prospective studies are
      therefore warranted to investigate the therapeutic impact of vitamin D
      supplementation in chronic liver disease.

PMID- 22634122
TI  - Chronic hepatitis B in children and adolescents.

PMID- 22634123
TI  - Assessment of risk for non-hepatic surgery in cirrhotic patients.

PMID- 22634124
TI  - Curiouser and curiouser!

PMID- 22634125
TI  - A randomized controlled trial of radiofrequency ablation and surgical resection
      in the treatment of small hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: The aim of this study was to compare the efficacy of
      radiofrequency ablation (RFA) with surgical resection (RES) in the treatment of
      small hepatocellular carcinoma (HCC). METHODS: A total of 168 patients with small
      HCC with nodular diameters of less than 4 cm and up to two nodules were randomly
      divided into RES (n=84) and RFA groups (n=84). Outcomes were carefully monitored
      and evaluated during the 3-year follow-up period. RESULTS: The 1-, 2-, and 3-year
      survival rates for the RES and RFA groups were 96.0%, 87.6%, 74.8% and 93.1%,
      83.1%, 67.2%, respectively. The corresponding recurrence-free survival rates for
      the two groups were 90.6%, 76.7%, 61.1% and 86.2%, 66.6%, 49.6%, respectively.
      There were no statistically significant differences between the two groups in
      overall survival rate (p=0.342) or recurrence-free survival rate (p=0.122).
      Multivariate analysis demonstrated that the independent risk factors associated
      with survival were multiple occurrences of tumors at different hepatic locations
      (relative risk of 2.696; 95% CI: 1.189-6.117; p=0.018) and preoperative
      indocyanine green retention rate at 15 min (ICG-15) (relative risk of 3.853; 95%
      CI: 1.647-9.015; p=0.002). CONCLUSIONS: In patients with small hepatocellular
      carcinomas, percutaneous RFA may provide therapeutic effects similar to those of
      RES. However, percutaneous RFA is more likely to be incomplete for the treatment
      of small HCCs located at specific sites of the liver, and open or laparoscopic
      surgery may be the better choice.

PMID- 22634126
TI  - Inflammasomes in liver diseases.
AB  - Inflammation is a common element in the pathogenesis of most chronic liver
      diseases that lead to fibrosis and cirrhosis. Inflammation is characterized by
      activation of innate immune cells and production of pro-inflammatory cytokines IL
      1alpha, IL-1beta, and TNFalpha. Inflammasomes are intracellular multiprotein
      complexes expressed in both parenchymal and non-parenchymal cells of the liver
      that in response to cellular danger signals activate caspase-1, and release IL
      1beta and IL-18. The importance of inflammasome activation in various forms of
      liver diseases in relation to liver damage, steatosis, inflammation and fibrosis
      is discussed in this review.

PMID- 22634127
TI  - Long-term clinical outcome of the surgically resected intraductal papillary
      neoplasm of the bile duct.
AB  - BACKGROUND & AIMS: Intraductal papillary neoplasm of the bile duct (IPNB) is a
      biliary neoplasm with predominant intraductal papillary growth and various
      degrees of malignant transformation. Although IPNB has been recently added to the
      WHO classification, the classification system needs refinements. METHODS: We
      retrospectively reviewed 93 non-invasive and invasive IPNB cases, surgically
      resected from 1996 to 2006. To further characterize their biologic behavior, we
      modified the WHO classification into a 4-tier category system in which non
      invasive IPNB cases with complex fused or cribriform papillae were separately
      designated. Epithelial types such as intestinal, gastric, pancreatobiliary, and
      oncocytic type were determined by morphology and mucin core protein
      immunohistochemistry. Resection margins were classified based on their
      microscopic appearances. The prognostic values of mucinous histology and MUC1
      protein expression were also determined. RESULTS: IPNB with complex fused or
      cribriform papillae showed a worse prognosis than IPNB with simple papillae and
      one such case showed a metachronous metastasis. In addition, a positive surgical
      margin including dysplasia was associated with worse outcomes. Among the invasive
      IPNB cases, MUC1-positive tumors were more aggressive than MUC1-negative tumors.
      CONCLUSIONS: We propose that non-invasive IPNB with complex fused or cribriform
      papillae might be better classified as mucosa-confined cholangiocarcinoma rather
      than IPNB with high grade dysplasia. In addition, aggressive further resection is
      recommended when a positive surgical margin including dysplasia is reported
      during intraoperative histopathological evaluation.

PMID- 22634128
TI  - Focus.

PMID- 22634129
TI  - X chromosomal mutations and spermatogenic failure.
AB  - The X and Y chromosomes, the sex chromosomes, are important key players in germ
      cell development. Both chromosomes contain genes that are uniquely expressed in
      male spermatogenesis. Furthermore, these chromosomes are special because men only
      have a single copy of them. These features make the sex chromosomes interesting
      for studying in view of spermatogenesis defects. The role of the Y chromosome,
      together with the presence of Yq microdeletions, in male infertility is well
      established. Less well-understood are the X-linked genes, their expression
      patterns and potential impact on male infertility. This review provides an
      overview of the current knowledge on potential spermatogenesis genes that are
      located on the mouse and human X chromosomes. A summary is given on knock-out
      mice models in which X-linked genes have been shown to alter spermatogenesis, and
      on genes that have been studied in humans. Finally, new research areas like miRNA
      analysis, Genome Wide Association Studies (GWAS) and array comparative genomic
      hybridisation (CGH) studies are discussed. This article is part of a Special
      Issue entitled: Molecular Genetics of Human Reproductive Failure.

PMID- 22634130
TI  - The genomics of the human endometrium.
AB  - The endometrium is a complex tissue that lines the inside of the endometrial
      cavity. The gene expression of the different endometrial cell types is regulated
      by ovarian steroids and paracrine-secreted molecules from neighbouring cells. Due
      to this regulation, the endometrium goes through cyclic modifications which can
      be divided simply into the proliferative phase, the secretory phase and the
      menstrual phase. Successful embryo implantation depends on three factors: embryo
      quality, the endometrium's state of receptivity, and a synchronised dialogue
      between the maternal tissue and the blastocyst. There is a need to characterise
      the endometrium's state of receptivity in order to prevent reproductive failure.
      No single molecular or histological marker for this status has yet been found.
      Here, we review the global transcriptomic analyses performed in the last decade
      on a normal human endometrium. These studies provide us with a clue about what
      global gene expression can be expected for a non-pathological endometrium. These
      studies have shown endometrial phase-specific transcriptomic profiles and common
      temporal gene expression patterns. We summarise the biological processes and
      genes regulated in the different phases of natural cycles and present other works
      on different conditions as well as a receptivity diagnostic tool based on a
      specific gene set profile. This article is part of a Special Issue entitled:
      Molecular Genetics of Human Reproductive Failure.

PMID- 22634131
TI  - Influence of mutations in hepatitis B virus surface protein on viral antigenicity
      and phenotype in occult HBV strains from blood donors.
AB  - BACKGROUND & AIMS: This study aimed at investigating mutations in the hepatitis B
      surface protein (HBsAg) in occult hepatitis B virus (HBV) infection (OBI) and
      their influence on viral antigenicity and phenotype. METHODS: The characteristics
      of 61 carriers with OBI (OBI group), 153 HBsAg(+) carriers with serum HBsAg <=
      100 IU/ml (HBsAg-L group) and 54 carriers with serum HBsAg >100 IU/ml (HBsAg-H
      group) from 38,499 blood donors were investigated. Mutations in the major
      hydrophilic region (MHR) of the viral sequences were determined. Thirteen
      representative MHR mutations observed in OBI sequences were antigenically
      characterized with a panel of monoclonal antibodies (MAbs) and commercial HBsAg
      immunoassays and functionally characterized in HuH7 cells and hydrodynamically
      injected mice. RESULTS: Of 61 OBI sequences, 34 (55.7%) harbored MHR mutations,
      which was significantly higher than the frequency in either the HBsAg-L (34.0%,
      p=0.003) or the HBsAg-H group (17.1%, p<0.001). Alterations in antigenicity
      induced by the 13 representative MHR mutations identified in the OBI group were
      assessed by reacting recombinant HBV mutants with 30 different MAbs targeting
      various epitopes. Four out of the 13 mutations (C124R, C124Y, K141E, and D144A)
      strongly decreased the analytical sensitivity of seven commercial HBsAg
      immunoassays, and 10 (G119R, C124Y, I126S, Q129R, S136P, C139R, T140I, K141E,
      D144A, and G145R) significantly impaired virion and/or S protein secretion in
      both HuH7 cells and mice. CONCLUSIONS: MHR mutations alter antigenicity and
      impair virion secretion, both of which may contribute to HBsAg detection failure
      in individuals with OBI.

PMID- 22634132
TI  - A review of multiple stressor studies that include ionising radiation.
AB  - Studies were reviewed that investigated the combined effects of ionising
      radiation and other stressors on non-human biota. The aim was to determine the
      state of research in this area of science, and determine if a review of the
      literature might permit a gross generalization as to whether the combined effects
      of multi-stressors and radiation are fundamentally additive, synergistic or
      antagonistic. A multiple stressor database was established for different organism
      groups. Information was collected on species, stressors applied and effects
      evaluated. Studies were mostly laboratory based and investigated two-component
      mixtures. Interactions declared positive occurred in 58% of the studies, while
      26% found negative interactions. Interactions were dependent on
      dose/concentration, on organism's life stage and exposure time and differed among
      endpoints. Except for one study, none of the studies predicted combined effects
      following Concentration Addition or Independent Action, and hence, no justified
      conclusions can be made about synergism or antagonism.

PMID- 22634133
TI  - Building a legacy for children and adolescents with chronic disease.
AB  - Children and adolescents who undergo extensive health-related treatment benefit
      from sharing their experience. Here, we describe how one institution established
      a legacy program for patients during their chronic disease treatment and how
      their journeys were symbolized with the distribution of beads. The legacy bead
      program was designed to be individualized according to the patient's journey and
      treatment experiences. A bead program offers a concrete, tangible method for
      patients to share their treatment journeys while building legacies on which they
      can reflect.

PMID- 22634134
TI  - On the alignment for precession electron diffraction.
AB  - Precession electron diffraction has seen a fast increase in its adoption as a
      technique for solving crystallographic structures as well as an alternative to
      conventional selected-area and converged-beam diffraction methods. One of the key
      issues of precession is the pivot point alignment, as a stationary apparent beam
      does not guarantee a fixed pivot point. A large precession tilt angle, along with
      pre-field and post-field misalignment, induces shift in the image plane. We point
      out here that the beam should be aligned to the pre-field optic axis to keep the
      electron illumination stationary during the rocking process. A practical
      alignment procedure is suggested with the focus placed on minimizing the beam
      wandering on the specimen, and is demonstrated for a (110)-oriented silicon
      single crystal and for a carbide phase (~20nm in size) within a cast cobalt
      chromium-molybdenum alloy.

PMID- 22634135
TI  - Differential phase contrast 2.0--opening new "fields" for an established
      technique.
AB  - Differential phase contrast microscopy has become known as a high resolution
      imaging technique for magnetic micro-structures in the past. The method senses
      the local induction by measuring the deflection of the probe beam after it passes
      through a specimen area carrying a magnetic field. Little attention has been
      paid, however, to the fact that this technique is also capable of measuring
      electric fields. An application of the technique to measure piezoelectric
      polarization fields inside multi-layered structures such as quantum wells is
      demonstrated. For this purpose, piezoelectric fields within non-centrosymmetric
      crystal structures, based on GaN/InGaN/GaN quantum wells, are investigated. It
      can be shown that the technique is sensitive to these fields and yields detailed
      information about the field distribution. The specific information and
      experimental limitations as well as artefacts of the technique will be discussed
      in detail and first measurements are shown. The main advantages turn out to be
      high sensitivity for electric fields, combined with a very high resolution, which
      is limited only by the STEM probe size. Another advantage is the large achievable
      field of view.

PMID- 22634136
TI  - Determination of the chemical composition of GaNAs using STEM HAADF imaging and
      STEM strain state analysis.
AB  - The nitrogen concentration of GaN(0.01<=x<=0.05)As(1-x) quantum wells was
      determined from high resolution scanning transmission electron microscopy
      (HRSTEM) images taken with a high-angle annular dark field (HAADF) detector. This
      was done by applying two independent methods: evaluation of the scattering
      intensity and strain state analysis. The HAADF scattering intensity was computed
      by multislice simulations taking into account the effect of static atomic
      displacements and thermal diffuse scattering. A comparison of the mean intensity
      per atom column on the experimental images with these simulations enabled us to
      generate composition maps with atomic scale resolution. STEM simulations of large
      supercells proved that local drops of the HAADF intensity observed close to
      embedded quantum wells are caused by surface strain relaxation. The same STEM
      images were evaluated by strain state analysis. We suggest a real space method
      which is not affected by fly-back errors in HRSTEM images. The results of both
      evaluation methods are in accordance with data obtained from X-ray diffraction
      measurements.

PMID- 22634137
TI  - Estrogen improves vascular function via peroxisome-proliferator-activated
      receptor-gamma.
AB  - The exact mechanism of estrogen in cardiovascular disease is not fully
      understood. As estrogen receptors (ERs), the peroxisome-proliferator-activated
      receptor-gamma (PPARgamma) belongs to the family of ligand activated nuclear
      receptors regulating atheroprotective genes. The aim of this project was to
      investigate whether vascular effects of estrogen are mediated via PPARgamma
      regulation in the vascular compartment. Estrogen deficient ovariectomized
      wildtype-mice (OVX) displayed significant reduction of PPARgamma-expression in
      aortic tissue compared to wildtype-mice with intact ovarian function (Sham).
      Hormone replacement with subdermal 17beta-estradiol pellets significantly
      increased vascular PPARgamma-expression in ovariectomized female wildtype-mice
      (OVX/E2). Analogous to wildtype-mice, estrogen-deficient OVX ApoE(-/-)-mice had
      low vascular PPARgamma-expression associated with ROS generation, endothelial
      dysfunction and atherogenesis. Estrogen replacement (OVX/E2) rescued vascular
      PPARgamma-expression, reduced ROS generation, monocyte recruitment,
      atherosclerotic lesion formation and improved endothelial function. Inhibition of
      PPARgamma by GW9662, a specific PPARgamma-antagonist reduced 17beta-estradiol
      mediated vascular effects (OVX/E2+GW9662). Finally, despite estrogen deficiency
      treatment with pioglitazone (OVX+pioglitazone), a selective PPARgamma-agonist,
      compensates deterioration of vascular morphology and function. 17beta-estradiol
      regulates vascular PPARgamma-expression in wildtype- and ApoE(-/-)-mice. The
      presented data demonstrate the fundamental relevance of PPARgamma as downstream
      target of 17beta-estradiol-related anti-inflammatory and atheroprotective effects
      within the vascular wall independent of its cardiovascular risk factor
      modifications.

PMID- 22634138
TI  - Dry powder inhaler formulation of lipid-polymer hybrid nanoparticles via
      electrostatically-driven nanoparticle assembly onto microscale carrier particles.
AB  - Lipid-polymer hybrid nanoparticles have emerged as promising nanoscale carriers
      of therapeutics as they combine the attractive characteristics of liposomes and
      polymers. Herein we develop dry powder inhaler (DPI) formulation of hybrid
      nanoparticles composed of poly(lactic-co-glycolic acid) and soybean lecithin as
      the polymer and lipid constituents, respectively. The hybrid nanoparticles are
      transformed into inhalable microscale nanocomposite structures by a novel
      technique based on electrostatically-driven adsorption of nanoparticles onto
      polysaccharide carrier particles, which eliminates the drawbacks of conventional
      techniques based on controlled drying (e.g. nanoparticle-specific formulation,
      low yield). First, we engineer polysaccharide carrier particles made up of
      chitosan cross-linked with tripolyphosphate and dextran sulphate to exhibit the
      desired aerosolization characteristics and physical robustness. Second, we
      investigate the effects of nanoparticle to carrier mass ratio and salt inclusion
      on the adsorption efficiency, in terms of the nanoparticle loading and yield,
      from which the optimal formulation is determined. Desorption of the nanoparticles
      from the carrier particles in phosphate buffer saline is also examined. Lastly,
      we characterize aerosolization efficiency of the nanocomposite product in vitro,
      where the emitted dose and respirable fraction are found to be comparable to the
      values of conventional DPI formulations.

PMID- 22634139
TI  - The effect of formulations and experimental conditions on in vitro human skin
      permeation-Data from updated EDETOX database.
AB  - In vitro methods are commonly used in order to estimate the extent of systemic
      absorption of chemicals through skin. Due to the wide variability of experimental
      procedures, types of skin and data analytical methods, the resulting permeation
      measures varies significantly between laboratories and individuals. Inter
      laboratory and inter-individual variations with the in vitro measures of skin
      permeation lead to unreliable extrapolations to in vivo situations. This
      investigation aimed at a comprehensive assessment of the available data and
      development of validated models for in vitro skin flux of chemicals under various
      experimental and vehicle conditions. Following an exhaustive literature review,
      the human skin flux data were collated and combined with those from EDETOX
      database resulting in a dataset of a total of 536 flux reports. Quantitative
      structure-activity relationship techniques combined with data mining tools were
      used to develop models incorporating the effects of permeant molecular structure,
      properties of the vehicle, and the experimental conditions including the membrane
      thickness, finite/infinite exposure, skin pre-hydration and occlusion. The work
      resulted in statistically valid models for estimation of the skin flux from
      varying experimental conditions, including relevant real-world mixture exposure
      scenarios. The models indicated that the most prominent factors influencing flux
      values were the donor concentration, lipophilicity, size and polarity of the
      penetrant, and the melting and boiling points of the vehicle, with skin occlusion
      playing significant role in a non-linear way. The models will aid assessment of
      the utility of dermal absorption data collected under different conditions with
      broad implications on transdermal delivery research.

PMID- 22634140
TI  - The influence of volatile solvents on transport across model membranes and human
      skin.
AB  - Simple topical formulations which include volatile components, such as gels or
      sprays, are appealing from a cosmetic perspective. However, complex formulation
      effects may result from the use of volatile excipients in topical formulations,
      particularly when applied at clinically relevant doses (typically less than a few
      mg cm(-2)). The present investigation aims to study the role of the volatile
      solvent ethanol (EtOH), in combination with Transcutol P((r)) (TC), dimethyl
      isosorbide (DMI) and isopropyl myristate (IPM), on the efficacy of dermal
      delivery of a model compound (i.e. methyl paraben). The methodology consisted of
      in vitro diffusion experiments conducted using silicone membranes and human
      epidermis. Finite dose studies were performed with two types of formulations:
      saturated solutions of methyl paraben in each vehicle alone and incorporating the
      volatile solvent in a 50:50 (v/v) proportion. The kinetics of EtOH evaporation
      from the formulations were also investigated by monitoring the weight loss of the
      formulation over time. The results showed that the presence of EtOH had little
      effect on the skin flux of methyl paraben compared with the corresponding
      saturated solutions. Formulations incorporating the volatile solvent were clearly
      more efficient, in line with the data obtained with silicone membranes.
      Furthermore, the permeation of methyl paraben from the saturated EtOH solution in
      both silicone and skin showed an initial period of relatively fast permeation,
      after which there was a marked decrease in the permeation rate. This reflected
      significant ethanol depletion from the formulation (chiefly by evaporation),
      causing most of the dose of methyl paraben applied to crystallise as a deposited
      film at the skin surface (observed experimentally and confirmed by mass balance
      studies), thus decreasing its availability to permeate. Studies of the kinetics
      of ethanol evaporation from the formulations confirm these findings,
      demonstrating a very short residence time of the volatile solvent at the surface
      of the membrane (approx. 6 min). In conclusion, the findings suggest that rapid
      evaporation of EtOH takes place from the formulations applied at the surface of
      the skin, leaving a saturated residue of the drug in the vehicle. The presence of
      EtOH clearly influenced the efficiency of the formulation, underlining the
      application of volatile components to optimise dermal delivery.

PMID- 22634142
TI  - The influence of menstrual phases on pain modulation in healthy women.
AB  - This study investigated if conditioned pain modulation (CPM) varies across the
      menstrual cycle in healthy, normally menstruating women and investigated
      correlations between sex hormone levels and CPM across the menstrual cycle.
      Thirty-six normally menstruating women were tested during 3 phases of the
      menstrual cycle: early follicular, ovulatory, and midluteal, confirmed by hormone
      determinations. Mechanical pressure (test stimulus) was applied to the masseter
      muscle and the induced pain assessed before, during, and after immersion of the
      hand into ice water (conditioning stimulus) to activate CPM or tepid water
      (control). Conditioning pain, ie, pain in the hand during CPM/control experiment,
      and tolerance time were also measured. Test pain intensity was suppressed during
      CPM in all phases (P < .001), but with more effective suppression during the
      ovulatry than during the early follicular phase (P < .05). There were no changes
      in test pain intensity during the control experiment and no significant
      differences in conditioning pain, or tolerance time between phases. In
      conclusion, our results showed more effective pain modulation in the ovulatory
      phase of the menstrual cycle, when estradiol levels are high and progesterone
      levels are low, than in the early follicular phase when both these hormones are
      low. PERSPECTIVE: Deficient pain modulation is believed to be an important
      pathogenic factor in many chronic pain conditions that affect women. This article
      shows that sex hormones modulate conditioned pain modulation, because pain
      inhibition was more effective in the ovulatory phase of the menstrual cycle than
      in the early follicular phase.

PMID- 22634141
TI  - A nipple shield delivery system for oral drug delivery to breastfeeding infants:
      microbicide delivery to inactivate HIV.
AB  - A new drug delivery method for infants is presented which incorporates an active
      pharmaceutical ingredient (API)-loaded insert into a nipple shield delivery
      system (NSDS). The API is released directly into milk during breastfeeding. This
      study investigates the feasibility of using the NSDS to deliver the microbicide
      sodium dodecyl sulfate (SDS), with the goal of preventing mother-to-child
      transmission (MTCT) of HIV during breastfeeding in low-resource settings, when
      there is no safer alternative for the infant but to breastfeed. SDS has been
      previously shown to effectively inactivate HIV in human milk. An apparatus was
      developed to simulate milk flow through and drug release from a NSDS. Using this
      apparatus milk was pulsed through a prototype device containing a non-woven fiber
      insert impregnated with SDS and the microbicide was rapidly released. The total
      SDS release from inserts ranged from 70 to 100% of the average 0.07 g load within
      50 ml (the volume of a typical breastfeed). Human milk spiked with H9/HIV(IIIB)
      cells was also passed through the same set-up. Greater than 99% reduction of cell
      associated HIV infectivity was achieved in the first 10 ml of milk. This proof of
      concept study demonstrates efficient drug delivery to breastfeeding infants is
      achievable using the NSDS.

PMID- 22634143
TI  - Comparison of chemical-induced changes in proliferation and apoptosis in human
      and mouse neuroprogenitor cells.
AB  - There is a need to develop rapid and efficient models to screen chemicals for
      their potential to cause developmental neurotoxicity. Use of in vitro neuronal
      models, including human cells, is one approach that allows for timely, cost
      effective toxicity screening. The present study compares the sensitivity of human
      (ReN CX) and mouse (mCNS) neuroprogenitor cell lines to chemicals using a
      multiplex assay for proliferation and apoptosis, endpoints that are critical for
      neural development. Cells were exposed to 0.001-100 MUM concentrations of 11
      chemicals (cadmium, chlorpyrifos oxon, dexamethasone, dieldrin, ketamine, lead,
      maneb, methylmercury, nicotine, trans-retinoic acid, and trimethyltin) reported
      in the literature to affect proliferation and/or apoptosis, and 5 chemicals
      (dimethyl pthalate, glyphosate, omeprazole, saccharin, and d-sorbitol) with no
      reports of effects on either endpoint. High-content screening of markers for
      proliferation (BrdU incorporation) and apoptosis (activated caspase 3 and p53)
      was used to assess the effect of chemicals in both cell lines. Of the chemicals
      tested, methylmercury, cadmium, dieldrin, chlorpyrifos oxon, trans-retinoic acid,
      and trimethyltin decreased proliferation by at least 50% of control in either the
      ReN CX or mCNS cells. None of the chemicals tested activated caspase 3 or p53 in
      the ReN CX cells, while methylmercury, cadmium, dieldrin, chlorpyrifos oxon,
      trimethyltin, and glyphosate all induced at least a doubling in these apoptotic
      markers in the mCNS cells. Compared to control, cadmium, trans-retinoic acid, and
      trimethyltin decreased cell viability (ATP levels) by at least 50% in the ReN CX
      cells, while cadmium, dieldrin, and methylmercury decreased viability by at least
      50% in the mCNS cells. Based on these results, BrdU is an appropriate marker for
      assessing chemical effects on proliferation, and human cells are more sensitive
      than mouse cells for this endpoint. By contrast, caspase 3 and p53 were altered
      by environmental chemicals in mouse, but not in human cells. Therefore, these
      markers are not appropriate to assess the ability of environmental chemicals to
      induce apoptosis in the ReN CX cells.

PMID- 22634144
TI  - Measurement of intracellular biomolecular oxidation in liver ischemia-reperfusion
      injury via immuno-spin trapping.
AB  - Hepatic ischemia-reperfusion (I/R) can lead to liver failure in association with
      remote organ damage, both of which have significant rates of morbidity and
      mortality. In this study, novel spin trapping and histopathological techniques
      have been used to investigate in vivo free radical formation in a rat model of
      warm liver I/R injury. 5,5-Dimethyl-1-pyrroline N-oxide (DMPO) was administered
      to rats via intraperitoneal injection at a single dose of 1.5g of pure DMPO/kg
      body wt 2h before the initiation of liver ischemia. Blood vessels supplying the
      median and left lateral hepatic lobes were occluded with an arterial clamp for
      60min, followed by 60min reperfusion. The effects of DMPO on I/R injury were
      evaluated by assessing the hepatic ultrastructure via transmission electron
      microscopy and by histopathological scoring. Immunoelectron microscopy was
      performed to determine the cellular localization of DMPO nitrone adducts. Levels
      of nitrone adducts were also measured to determine in situ scavenging of protein
      and DNA radicals. Total histopathological scoring of cellular damage was
      significantly decreased in hepatic I/R injury after DMPO treatment. DMPO
      treatment significantly decreased the hepatic conversion of xanthine oxidase and
      4-hydroxynonenal formation in I/R injury compared to the untreated I/R group. The
      distribution of gold-nanoparticle-labeled DMPO nitrone adducts was observed in
      mitochondria, cytoplasm, and nucleus of hepatocytes. The formation of protein-
      and DNA-nitrone adducts was increased in DMPO-treated I/R livers compared to DMPO
      controls, indicating increased in situ protein and DNA radical formation and
      scavenging by DMPO. These results suggest that DMPO reduces I/R damage via
      protection against oxidative injury.

PMID- 22634147
TI  - P38 MAP kinase functions as a switch in MS-275-induced reactive oxygen species
      dependent autophagy and apoptosis in human colon cancer cells.
AB  - MS-275 is a synthetic benzamide derivative of the histone deacetylase inhibitor
      and is currently in phase I/II clinical trials. Many reports have shown that the
      anti-tumor activity of MS-275 in several types of cancer is mainly attributable
      to its capacity to induce the apoptotic death of tumor cells. It remains unclear
      if autophagy is involved in MS-275 treatment of cancer cells. Here, we first show
      that MS-275 induces human colon cancer cell HCT116 autophagy as well as
      apoptosis. Short-term treatment (24h) induced HCT116 cells to undergo autophagy
      with dependence on intracellular reactive oxygen species production and ERK
      activation. The activated reactive oxygen species/ERK signal promoted Atg7
      protein expression, which triggered MS-275-induced cancer cell autophagy.
      However, after prolonged treatment with MS-275 (over 48h), autophagic cells
      turned apoptotic, which was also dependent on reactive oxygen species generation.
      Interestingly, we found that p38 MAP kinase played a vital role in the switch
      from autophagy to apoptosis in MS-275-induced human colon cancer cells. High
      expression of p38 induced cell autophagy, but low expression resulted in
      apoptosis. In addition, observations in vivo are strongly consistent with the in
      vitro results. Therefore, these findings extend our understanding of the action
      of MS-275 in inducing cancer cell death and suggest that it may be a promising
      clinical chemotherapeutic agent with multiple effects.

PMID- 22634145
TI  - Transforming growth factor beta suppresses glutamate-cysteine ligase gene
      expression and induces oxidative stress in a lung fibrosis model.
AB  - The concentration of glutathione (GSH), the most abundant intracellular free
      thiol and an important antioxidant, is decreased in the lung in both fibrotic
      diseases and experimental fibrosis models. The underlying mechanisms and
      biological significance of GSH depletion, however, remain unclear. Transforming
      growth factor beta (TGF-beta) is the most potent and ubiquitous profibrogenic
      cytokine and its expression is increased in almost all fibrotic diseases. In this
      study, we show that increasing TGF-beta1 expression in mouse lung to a level
      comparable to those found in lung fibrotic diseases by intranasal instillation of
      AdTGF-beta1(223/225), an adenovirus expressing constitutively active TGF-beta1,
      suppressed the expression of both catalytic and modifier subunits of glutamate
      cysteine ligase (GCL), the rate-limiting enzyme in de novo GSH synthesis,
      decreased GSH concentration, and increased protein and lipid peroxidation in
      mouse lung. Furthermore, we show that increasing TGF-beta1 expression activated
      JNK and induced activating transcription factor 3, a transcriptional repressor
      involved in the regulation of the catalytic subunit of GCL, in mouse lung.
      Control virus (AdDL70-3) had no significant effect on any of these parameters,
      compared to saline-treated control. Concurrent with GSH depletion, TGF-beta1
      induced lung epithelial apoptosis and robust pulmonary fibrosis. Importantly,
      lung GSH levels returned to normal, whereas fibrosis persisted at least 21 days
      after TGF-beta1 instillation. Together, the data suggest that increased TGF-beta1
      expression may contribute to the GSH depletion observed in pulmonary fibrosis
      diseases and that GSH depletion may be an early event in, rather than a
      consequence of, fibrosis development.

PMID- 22634146
TI  - Anti-malarial drug artesunate ameliorates oxidative lung damage in experimental
      allergic asthma.
AB  - Oxidative stress is a critical pathophysiological factor in the development of
      allergic airway inflammation, resulting in oxidative damage to lipids, proteins,
      and DNA. Our recent report revealed potent anti-inflammatory effects of the
      antimalarial drug artesunate in experimental allergic asthma. The present study
      investigated potential antioxidative effects of artesunate in a murine model of
      allergic asthma in comparison with dexamethasone, a potent corticosteroid. Mice
      were sensitized and challenged with ovalbumin and developed airway inflammation
      and oxidative lung damage. Artesunate markedly suppressed ovalbumin-induced
      increases in total cell, eosinophil, and neutrophil counts. In contrast,
      dexamethasone failed to inhibit neutrophil recruitment. Levels of the oxidative
      damage markers 8-isoprostane, 8-hydroxy-2-deoxyguanosine, and 3-nitrotyrosine
      were potently repressed by artesunate. However, dexamethasone showed weaker
      inhibitory effects on 3-nitrotyrosine production. Ovalbumin-induced increases in
      the expression of the pro-oxidants iNOS and NADPH oxidase (NOX1, 2, 3, and 4)
      were significantly abated by artesunate. Gene expression of regulatory subunits
      of NOX, p22phox and p67phox, was also reduced by artesunate. The expression and
      activities of the antioxidants superoxide dismutase and catalase were
      substantially reversed with artesunate in ovalbumin-challenged mice. Artesunate
      significantly enhanced nuclear levels of nuclear factor erythroid-2-related
      factor 2 (Nrf2) in lung tissues from ovalbumin-challenged mice and in TNF-alpha
      stimulated human bronchial epithelial cells. Our findings implicate a potential
      therapeutic value for artesunate in the treatment of asthma via the amelioration
      of oxidative damage in allergic airways, and it may act by suppressing pro
      oxidants and restoring the activities and expression of antioxidants via
      activation of Nrf2. Artesunate may be a potential novel anti-asthma drug capable
      of controlling both inflammation and oxidative damage in chronic severe asthma.

PMID- 22634148
TI  - Role of mtDNA haplogroups in COPD susceptibility in a southwestern Han Chinese
      population.
AB  - The interplay of a complex genetic basis with the environmental factors of
      chronic obstructive pulmonary disease (COPD) may account for the differences in
      individual susceptibility to COPD. Mitochondrial DNA (mtDNA) contributes to an
      individual's ability to resist oxidation, an important determinant that affects
      COPD susceptibility. To investigate whether mtDNA haplogroups play important
      roles in COPD susceptibility, the frequencies of mtDNA haplogroups and an 822-bp
      mtDNA deletion in 671 COPD patients and 724 control individuals from southwestern
      China were compared. Multivariate logistic regression analysis revealed that,
      whereas mtDNA haplogroups A and M7 might be associated with an increased risk for
      COPD (OR=1.996, 95% CI=1.149-2.831, p=0.006, and OR=1.754, 95% CI=1.931-2.552,
      p=0.021, respectively), haplogroups F, D, and M9 might be associated with a
      decreased risk for COPD in this population (OR=0.554, 95% CI=0.390-0.787,
      p=0.001; OR=0.758, 95% CI=0.407-0.965, p=0.002; and OR=0.186, 95% CI=0.039-0.881,
      p=0.034, respectively). Additionally, the increased frequency of the 822-bp mtDNA
      deletion in male cigarette-smoking subjects among COPD patients and controls of
      haplogroup D indicated that haplogroup D might increase an individual's
      susceptibility to DNA damage from external reactive oxygen species derived from
      heavy cigarette smoking. We conclude that haplogroups A and M7 might be risk
      factors for COPD, whereas haplogroups D, F, and M9 might decrease the COPD risk
      in this Han Chinese population.

PMID- 22634149
TI  - 3,3'-Dihydroxyisorenieratene and isorenieratene prevent UV-induced DNA damage in
      human skin fibroblasts.
AB  - Skin cancer is among the most frequent neoplastic malignancies and exposure to UV
      irradiation is a major risk factor. In addition to topical sunscreens,
      photoprotection by dietary antioxidants such as carotenoids or polyphenols has
      been suggested as a means of prevention. Isorenieratene (IR) and
      dihydroxyisorenieratene (DHIR) are aromatic carotenoids with particular
      antioxidant properties produced by Brevibacterium linens. The aim of this study
      was to investigate the photoprotective and antioxidant activities of DHIR and IR
      in comparison to the nonaromatic carotenoid lutein in human dermal fibroblasts.
      Incubation of the cells with DHIR and IR significantly decreased the UV-induced
      formation of cyclobutane pyrimidine dimers and formation of DNA strand breaks.
      Lipid oxidation was lowered as determined by the formation of malondialdehyde as
      a biomarker. Both aromatic carotenoids also prevented oxidatively generated
      damage to DNA as demonstrated by a decrease in DNA strand breaks associated with
      the formation of oxidized DNA bases. These data highlight the multifunctional
      photoprotective properties of aromatic carotenoids, which may be suitable natural
      compounds for the prevention of skin cancer.

PMID- 22634150
TI  - Intravenous versus enteral nimodipine in aneurysmal subarachnoid hemorrhage: is
      there an advantage?

PMID- 22634151
TI  - Plants versus tumors: the search for new targets in neuro-oncology.

PMID- 22634152
TI  - Intra-operative computed-tomography-like real-time three-dimensional ultrasound
      in neurosurgery.

PMID- 22634153
TI  - Benefit of CT scanning for assessing pulmonary disease in the immunodepressed
      patient.
AB  - INTRODUCTION: Management of pulmonary disease in immunodepressed patients
      requires a clear diagnostic and therapeutic strategy and multidisciplinary
      cooperation. DISCUSSION: The diagnostic approach should take into account the
      type of immunodepression, the clinical picture, the radiological signs and
      symptoms, and the microbiological, cytological and even histological examination
      of the pulmonary or extrapulmonary specimens. The high-resolution CT scan plays a
      central role and makes it possible to prioritize the diagnostic possibilities.
      CONCLUSION: The analysis of the literature shows three important points: the
      chest X-ray has low diagnostic value; the CT scan of the chest can reveal lesions
      that cannot be detected on a standard chest X-ray; the CT scan is helpful for
      early detection and monitoring of invasive pulmonary aspergillosis.

PMID- 22634154
TI  - Pigment-producing granulomatous myopathy in Atlantic salmon: a novel inflammatory
      response.
AB  - Melanin comprises a complex group of pigmented polymers whose primary function is
      ascribed to dermal solar protection, but may also have an interesting role in
      innate immunity. In ectothermic vertebrates, melanogenesis is reported in
      leukocyte populations, but it is not known if this occurs in connection with
      inflammatory reactions. Melanin accumulations in ectopic locations, in particular
      muscle, represent a serious quality problem in salmon production. Here, we
      investigated such changes for the expression of dopachrome tautomerase and
      tyrosinase as well as some important immune genes and pathogens. Furthermore, the
      nature of the pathological changes was addressed by morphological methods. Gene
      transcripts encoding key enzymes in melanogenesis, suggesting a de novo melanin
      synthesis in pigmented muscle, were found. MHC class II transcripts were up
      regulated and there was no indication of bacterial or viral infection. The
      histological examination revealed granulomatous inflammation with distribution of
      MHC class II positive cells and T cells, analogous to the pattern found in
      mammals. Importantly, in contrast to mammals pigmented cells were contributing in
      the inflammation. We demonstrate that melanin production occurs in granulomatous
      inflammation in salmon, revealing a close and hitherto unreported link between
      the pigmentary and immune systems.

PMID- 22634155
TI  - Mycotoxin production by Aspergillus niger aggregate strains isolated from
      harvested maize in three Portuguese regions.
AB  - BACKGROUND: Maize is considered one of the crops more susceptible to mycotoxins
      in the world. Two of the mycotoxins commonly associated with maize are fumonisins
      and ochratoxin A. Aspergillus niger is a known producer of ochratoxin A and is
      easily found in maize. Recently, however, A. niger has been reported to produce
      as well fumonisins, mainly fumonisin B(2). AIMS: The aim of this study was to
      isolate A. niger strains from maize samples collected in three Portuguese maize
      growing regions and to detect the production of both fumonisin B(2) and
      ochratoxin A. METHODS: Ninety five maize samples were collected, plated, and all
      observable Aspergillus section Nigri strains were isolated. Strains were
      morphologically characterized and mycotoxin production was determined by HPLC-FD.
      RESULTS: Isolations resulted in a total of 270 strains of black Aspergillus from
      73 samples (77% of the samples). About 14% of those strains were found to produce
      ochratoxin A and 39% of the strains were found to produce fumonisin B(2).
      CONCLUSIONS: An association between the production of these two mycotoxins could
      not be found and no conclusions could be taken whether the presence of A. niger
      aggregate strains will increase the risk of maize contamination with fumonisins
      and more specifically with fumonisin B(2).

PMID- 22634156
TI  - Sodium (Na+) concentration effects on metabolic pathway and estimation of ATP use
      in dark fermentation hydrogen production through stoichiometric analysis.
AB  - Batch experiments were conducted to investigate the effects of Na(+)
      concentration on hydrogen production with dark fermentation. The Na(+)
      concentration was varied from 0 to 8 g/L in the mixed culture using an anaerobic
      sludge treated by acid. The maximum hydrogen production was achieved with 1 g
      Na(+)/L, whereas the hydrogen production was decreased over 2 g-Na(+)/L due to
      the inhibitory of Na(+). The mechanisms of Na(+) inhibition to the hydrogen
      production are studied using pure culture of Clostridium butyricum by calculating
      the energy balance. At a high sodium concentration, C. butyricum used a greater
      proportion of the ATP generated via fermentation for cell maintenance rather than
      for cell synthesis. Additionally, higher Na(+) concentrations shifted the
      fermentation process toward the acetate synthesis pathway instead of the butyrate
      pathway, and the value of Y(X/ATP) decreased. With high Na(+) concentrations, a
      greater ratio of hydrogen was produced via the oxidation of NADH. Excess hydrogen
      production decreased as the Na(+) concentration increased.

PMID- 22634157
TI  - Mediation of adoption and use: a key strategy for mitigating unintended
      consequences of health IT implementation.
AB  - OBJECTIVE: Without careful attention to the work of users, implementation of
      health IT can produce new risks and inefficiencies in care. This paper uses the
      technology use mediation framework to examine the work of a group of nurses who
      serve as mediators of the adoption and use of a barcode medication administration
      (BCMA) system in an inpatient setting. MATERIALS AND METHODS: The study uses
      ethnographic methods to explore the mediators' work. Data included field notes
      from observations, documents, and email communications. This variety of sources
      enabled triangulation of findings between activities observed, discussed in
      meetings, and reported in emails. RESULTS: Mediation work integrated the BCMA
      tool with nursing practice, anticipating and solving implementation problems.
      Three themes of mediation work include: resolving challenges related to
      coordination, integrating the physical aspects of BCMA into everyday practice,
      and advocacy work. DISCUSSION: Previous work suggests the following factors
      impact mediation effectiveness: proximity to the context of use, understanding of
      users' practices and norms, credibility with users, and knowledge of the
      technology and users' technical abilities. We describe three additional factors
      observed in this case: 'influence on system developers,' 'influence on
      institutional authorities,' and 'understanding the network of organizational
      relationships that shape the users' work.' CONCLUSION: Institutionally supported
      clinicians who facilitate adoption and use of health IT systems can improve the
      safety and effectiveness of implementation through the management of unintended
      consequences. Additional research on technology use mediation can advance the
      science of implementation by providing decision-makers with theoretically
      durable, empirically grounded evidence for designing implementations.

PMID- 22634158
TI  - Genomic perspectives in inter-individual adverse responses following nanomedicine
      administration: The way forward.
AB  - The underlying mechanism of intravenous infusion-related adverse reactions
      inherent to regulatory-approved nanomedicines still remains elusive. There are
      substantial inter-individual differences in observed adverse reactions, which may
      include cardiovascular, broncho-pulmonary, muco-cutaneous, neuro-psychosomatic
      and autonomic manifestations. Although nanomedicine-mediated triggering of
      complement activation has been suggested to be a significant contributing factor
      to these adverse events, complement activation may still proceed in non
      responders. Whether these reactions share similar immunological mechanisms and
      underpinning genetic factors with drug hypersensitivity syndrome remains to be
      investigated. Genetic association studies could be a powerful tool to dissect
      causative factors and reveal the multiple molecular pathways that induce infusion
      related adverse reactions. It is envisaged that such research may lead to the
      design of reliable in vitro profiling tests for risk assessment and treatment
      decisions, thereby revolutionizing the practice of medicine with
      nanopharmaceuticals. Such procedures may further improve regulatory approval
      processes for nanomedicines currently in the pipeline and decrease the overall
      cost of health care. Here we discuss some key innate immunity genes and their
      polymorphisms in relation to nanomedicine infusion-mediated symptomatic
      responses.

PMID- 22634159
TI  - Perspectives on carbon nanotube-mediated adverse immune effects.
AB  - Carbon nanotubes are entities of different morphology and aspect ratios with
      anisotropic character. Due to their unique electronic, photonic, mechanical and
      chemical properties, carbon nanotubes are receiving increasing attention in
      nanomedicine research where examples include site-specific drug and nucleic acid
      delivery, photodynamic therapy and photoacoustic molecular imaging. The
      interaction of carbon nanotubes with the immune system, which plays a key role in
      the recognition and elimination of foreign materials, and consequential
      responses, is of central importance for the proposed successful biomedical
      applications of nanotubes. Research in this avenue, however, is scant and the
      limited available data are rather contradictory. In this progress article we have
      collected some of the most important experimental results obtained thus far on
      carbon nanotube-mediated immune toxicity with an emphasis on cardiovascular
      exposure, including activation of the complement system, macrophage recognition
      and clearance, and overall effects on the functionality of different immune
      cells. Mapping these immune-related risks as well as understanding their
      molecular mechanisms is a crucial step in the development of any carbon nanotube
      containing nanopharmaceuticals.

PMID- 22634161
TI  - Cationic lipids activate intracellular signaling pathways.
AB  - Cationic liposomes are commonly used as a transfection reagent for DNA, RNA or
      proteins and as a co-adjuvant of antigens for vaccination trials. A high density
      of positive charges close to cell surface is likely to be recognized as a signal
      of danger by cells or contribute to trigger cascades that are classically
      activated by endogenous cationic compounds. The present review provides evidence
      that cationic liposomes activate several cellular pathways like pro-apoptotic and
      pro-inflammatory cascades. An improved knowledge of the relationship between the
      cationic lipid properties (nature of the lipid hydrophilic moieties, hydrocarbon
      tail, mode of organization) and the activation of these pathways opens the way to
      the use and design of cationic tailored for a specific application (e.g. for gene
      transport or as adjuvants).

PMID- 22634162
TI  - Induction of RNA interference genes by double-stranded RNA; implications for
      susceptibility to RNA interference.
AB  - Gene silencing by RNA interference (RNAi) can be a useful reverse genetics tool
      in eukaryotes. However, some species appear refractory to RNAi. To study the role
      of the differential expression of RNAi proteins in RNAi, we isolated partial
      dicer-2, argonaute-2 translin, vasa intronic gene (VIG) and tudor
      staphylococcus/micrococcal nuclease (TSN) genes from the tobacco hornworm,
      Manduca sexta, a well-studied insect model which we have found to be variably
      sensitive to RNAi. We found that the RNAi gene, translin, was expressed at
      minimal levels in M. sexta tissue and that there is a specific, dose-dependent
      upregulation of dicer-2 and argonaute-2 expression in response to injection with
      dsRNA, but no upregulation of the other genes tested. Upregulation of gene
      expression was rapid and transient. In order to prolong the upregulation we
      introduced multiple doses of dsRNA, resulting in multiple peaks of dicer-2 gene
      expression. Our results have implications for the design of RNAi experiments and
      may help to explain differences in the sensitivity of eukaryotic organisms to
      RNAi.

PMID- 22634160
TI  - Biocompatibility assessment of Si-based nano- and micro-particles.
AB  - Silicon is one of the most abundant chemical elements found on the Earth. Due to
      its unique chemical and physical properties, silicon based materials and their
      oxides (e.g. silica) have been used in several industries such as building and
      construction, electronics, food industry, consumer products and biomedical
      engineering/medicine. This review summarizes studies on effects of silicon and
      silica nano- and micro-particles on cells and organs following four main exposure
      routes, namely, intravenous, pulmonary, dermal and oral. Further, possible
      genotoxic effects of silica based nanoparticles are discussed. The review
      concludes with an outlook on improving and standardizing biocompatibility
      assessment for nano- and micro-particles.

PMID- 22634163
TI  - Chitin synthase 1 gene and its two alternative splicing variants from two sap
      sucking insects, Nilaparvata lugens and Laodelphax striatellus (Hemiptera:
      Delphacidae).
AB  - Chitin synthase (CHS) is an enzyme that is required for chitin formation in
      insect cuticles and other tissues. In this study, CHS genes from two destructive
      rice insect pests, the brown planthopper Nilaparvata lugens and the small brown
      planthopper Laodelphax striatellus, were cloned. Phylogenetic analysis showed
      that these genes belonged to class CHS1 of the CHS gene family. Most insects
      possess two CHS genes (CHS1 and CHS2); however, genome and transcriptome searches
      showed that N. lugens possibly possess only CHS1 in both databases. Two
      transcript variants (CHS1a and CHS1b) resulting from exclusively alternative
      splicing (exon 19a or 19b in N. lugens) were identified for each of the two rice
      planthopper CHS1s. Gene structure comparison using the genomes that are currently
      sequenced showed that the CHS1 genes in all insects except Acyrthosiphon pisum
      have two transcript variants. Transcription of NlCHS1a reached its highest level
      just after molting, whereas NlCHS1b reached its highest expression level 1-2 days
      before molting. Injection of the N. lugens nymphs with double-strand RNA (dsRNA)
      of CHS1, CHS1a and CHS1b reduced the corresponding variant transcript levels and
      exhibited subsequent phenotypes. Silencing of CHS1 and CHS1a resulted in
      elongated distal wing pads and the "wasp-waisted" or crimpled cuticle phenotypes
      and eventually died, whereas the phenotypes caused by injection of NlCHS1b dsRNA
      seem not so obvious although slightly increased mortality was observed. Our
      results suggest that N. lugens likely lacks CHS2 and CHS1 may be efficient target
      gene for RNAi-based N. lugens control.

PMID- 22634164
TI  - Chronic administration of the selective P2X3, P2X2/3 receptor antagonist, A
      317491, transiently attenuates cancer-induced bone pain in mice.
AB  - The purinergic P2X3 and P2X2/3 receptors are in the peripheral nervous system
      almost exclusively confined to afferent sensory neurons, where they are found
      both at peripheral and central synapses. The P2X3 receptor is implicated in both
      neuropathic and inflammatory pain. However, the role of the P2X3 receptor in
      chronic cancer-induced bone pain is less known. Here we investigated the effect
      of systemic acute and chronic administration of the selective P2X3, P2X2/3
      receptor antagonist (5-[[[(3-Phenoxyphenyl)methyl][(1S)-1,2,3,4-tetrahydro-1
      naphthalenyl]amino]carbonyl]-1,2,4-benzenetricarboxylic acid sodium salt hydrate)
      (A-317491) in a murine model of cancer-induced bone pain. Chronic administration
      of A-317491 (30 MUmol/kgs.c., b.i.d.) resulted in a transient attenuation of pain
      related behaviours in the early stage of the bone cancer model, but had no effect
      in the late and more progressed stage of bone cancer. Also, acute administration
      of A-317491 (100 MUmol/kgs.c.) had no effect in the progressed stage of the bone
      cancer pain model. Thus, systemically administered A-317491 did not demonstrate a
      robust effect in the present mouse model of cancer-induced bone pain.

PMID- 22634165
TI  - Splitomicin inhibits fMLP-induced superoxide anion production in human
      neutrophils by activate cAMP/PKA signaling inhibition of ERK pathway.
AB  - Splitomicin, is a cell-permeable lactone derived from naphthol and known to be a
      potent selective inhibitor of Sir2 (silent information regulator 2). Previous
      studies have demonstrated that naphtholic compounds possess an inhibitory effect
      on neutrophils. Here, we present our investigation on the inhibitory effects of
      splitomicin in human neutrophils. The primary goal of our study was to locate a
      possible candidate on inflammatory reactions and to hopefully develop a novel
      anti-inflammatory therapy. Neutrophils were prepared following standard
      procedures. Neutrophils induced by either fMLP (1 MUM) or PMA (100 nM) were
      observed using a flow cytometer and the intracellular production of superoxide
      anions was investigated at different splitomicin concentrations. The cytosolic
      Ca(++) influx concentration was measured using a fluorescence spectrophotometer,
      and Mac-1 expression was detected with a flow cytometer. The MAP kinases were
      measured using western blotting. Our results showed that splitomicin inhibited
      superoxide anion production by fMLP (1 MUM) and NaF (20mM) in a concentration
      dependent manner (37.5-450 MUM). Splitomicin (300 and 450 MUM) also suppressed
      fMLP-induced intracellular calcium ion mobilization and extracellular-signal
      regulated kinase (ERK) phosphorylation. Moreover, splitomicin could inhibit fMLP
      induced Mac-1 expression and increase cAMP levels in human neutrophils. Our data
      demonstrated that splitomicin exhibits a noticeable inhibitory effect on
      superoxide anion production in human neutrophils. This negative effect was well
      correlated with increased cAMP levels via PKA activity and the subsequent
      inhibition of ERK (p42/p44) phosphorylation to decrease superoxide anion
      production.

PMID- 22634166
TI  - Vas deferens smooth muscle responses to the nitric oxide-independent soluble
      guanylate cyclase stimulator BAY 41-2272.
AB  - The nitric oxide-cGMP signaling pathway modulates the ejaculatory functions. The
      nitric oxide (NO)-independent soluble guanylate cyclase haem-dependent stimulator
      BAY 41-2272 potently relaxes different types of smooth muscles. However, no study
      investigated its effects in vas deferens smooth muscle. Therefore, we designed
      experiments to evaluate the in vitro relaxing responses of vas deferens to BAY 41
      2272. The effects of prolonged oral intake with BAY 41-2272 in vas deferens
      contractions of rats treated chronically with the NO synthase inhibitor N(omega)
      nitro-L-arginine methyl ester (L-NAME) were also investigated. BAY 41-2272 (0.001
      100 MUM) produced concentration-dependent relaxations in the prostatic and
      epididymal portions of vas deferens, an effect markedly reduced by the soluble
      guanylate cyclase inhibitor ODQ (100 MUM). BAY 41-2272 significantly increased
      cGMP levels that were fully prevented by ODQ. In separate protocols, rats
      received L-NAME (20mg/rat/day) concomitantly with BAY 41-2272 (10mg/kg/day, 4
      weeks), after which vas deferens contractions to electrical-field stimulation and
      noradrenaline were achieved. Electrical-field stimulation (1-32 Hz) evoked
      frequency-dependent contractions that were significantly enhanced in L-NAME
      treated rats. Co-treatment with BAY 41-2272 fully reversed the increased
      contractile responses in L-NAME group. Noradrenaline (0.01-100 MUM)-induced
      contractions were also greater in L-NAME-treated rats, and that was normalized by
      BAY 41-2272. In conclusion, BAY 41-2272 potently relaxes in vitro rat vas
      deferens smooth muscle and elevates the cGMP levels in an ODQ-sensitive manner.
      Moreover, prolonged oral intake with BAY 41-2272 restores the enhanced
      contractile vas deferens activity in rats treated with L-NAME. NO-independent
      soluble guanylate cyclase stimulators may be an alternative treatment for
      premature ejaculation.

PMID- 22634167
TI  - Pretreatment with interleukin-6 small interfering RNA can improve the survival
      rate of polymicrobial cecal ligation and puncture mice by down regulating
      interleukin-6 production.
AB  - Interleukin-6 (IL-6) is considered to be an early marker of severe sepsis that is
      associated with increased morbidity and mortality. Therefore, we pretreated male
      ICR mice with IL-6 small interfering RNA (siRNA) before cecal ligation and
      puncture (CLP) and observed the changes in their survival in response to down
      regulation of IL-6, as well as the role of Th subsets during sepsis. In addition,
      sham and CLP operated mice were sacrificed at different time points to determine
      the serum IL-6 levels during early and late sepsis. IL-6 siRNA pretreated septic
      mice showed markedly extended survival (23.3%) up to 10 days and significantly
      reduced serum IL-6 levels at day 5 (209.90 +/- 0.50 pg/ml; P<0.0001) when
      compared to CLP mice at day 1. Furthermore, IL-6 mRNA and protein were highly
      expressed during early sepsis in CLP mice at day 1 and mRNA was not detected in
      IL-6 siRNA treated CLP mice at days 1 or 5 and serum level of IL-6 was also
      decreased significantly (P<0.01). In addition, the mRNA expression of C5aR, ROR
      gammat, PU.1 and protein expression of IL-17 were high at day 5 in IL-6 siRNA
      treated mice. Taken together, the results of the present study demonstrate that
      pretreatment with IL-6 siRNA improved CLP induced septic mice survival.
      Furthermore, the IL-6 level was down-regulated and the transcription factors ROR
      gammat and PU.1 were up-regulated by IL-6 siRNA at late sepsis. The results
      presented herein also suggest that IL-6 siRNA could be a potential molecular
      therapeutic strategy for the treatment of sepsis.

PMID- 22634168
TI  - Colchicine effectively and safely treats acute pericarditis and prevents and
      treats recurrent pericarditides.

PMID- 22634169
TI  - Late coronary sequels of Kawasaki disease.

PMID- 22634170
TI  - Mild-to-moderate functional tricuspid regurgitation in patients undergoing valve
      replacement for rheumatic mitral disease: the influence of tricuspid valve repair
      on clinical and echocardiographic outcomes.

PMID- 22634172
TI  - Inappropriate restrictions on life saving technology.

PMID- 22634173
TI  - IFITM1 increases osteogenesis through Runx2 in human alveolar-derived bone marrow
      stromal cells.
AB  - The exact molecular mechanisms governing the differentiation of bone marrow
      stromal stem/progenitor cells (BMSCs) into osteoblasts remain largely unknown. In
      this study, a highly expressed protein that had a high degree of homology with
      interferon-induced transmembrane protein 1 (IFITM1) was identified using
      differentially expressed gene (DEG) screening. We sought to determine whether
      IFITM1 influenced osteoblast differentiation. During differentiation, IFITM1
      expression gradually increased from 5 to 10days and subsequently decreased at 15
      days in culture. Analysis of IFITM1 protein expression in several cell lines as
      well as in situ studies on human tissues revealed its selective expression in
      bone cells and human bone. Proliferation of human alveolar-derived bone marrow
      stromal cells (hAD-BMSCs) was significantly inhibited by IFITM1 knockdown by
      using short hairpin RNA, as were bone specific markers such as alkaline
      phosphatase, collagen type I alpha 1, bone sialoprotein, osteocalcin, and osterix
      were decreased. Calcium accumulation also decreased following IFITM1 knockdown.
      Moreover, IFITM1 knockdown in hAD-BMSCs was associated with inhibition of Runx2
      mRNA and protein expression. Collectively, the present data provide evidence for
      the role of IFITM1 in osteoblast differentiation. The exact mechanisms of
      IFITM1's involvement in osteoblast differentiation are still under investigation.

PMID- 22634174
TI  - Structural disorder in proteins brings order to crystal growth in
      biomineralization.
AB  - Biomineralization, the generation of hard tissues of living organisms, is a
      process strictly regulated by hormones, enzymes and a range of regulatory
      proteins of which several resisted structural characterization thus far. Without
      actual generalizations, there have been scattered observations in the literature
      for the structural disorder of these proteins. To address this issue in general,
      we have collected SwissProt proteins involved in the formation of bone and teeth
      in vertebrates, annotated for biomineralization. All these proteins show an
      extremely high level of predicted disorder (with a mean of 53%), making them the
      most disordered functional class of the protein world. Exactly the same feature
      was established for evolutionarily more distant proteins involved in the
      formation of the silica wall of marine diatoms and the shell of oysters and other
      mollusks. Because these proteins also show an extremely biased amino acid
      composition, such as high negative charge, high frequency of Ser and Asp or Pro
      residues and repetitiveness, we also carried out a database search with these
      sequence features for further proteins. This search uncovered several further
      disordered proteins with clearly related functions, although their annotations
      made no mention of biomineralization. This general and very strong correlation
      between biomineralization, structural disorder of proteins and particular
      sequence features indicates that regulated growth of mineral phase in biology can
      only be achieved by the assistance of highly disordered proteins.

PMID- 22634175
TI  - Atypical femur fractures among breast cancer and multiple myeloma patients
      receiving intravenous bisphosphonate therapy.
AB  - PURPOSE: Atypical femur fractures represent a potential complication of chronic
      oral bisphosphonate therapy in women with osteoporosis, but the risk of atypical
      femur fractures among cancer patients receiving intravenous bisphosphonates at
      higher cumulative doses remains unclear. We examined femur fractures occurring in
      cancer patients treated with intravenous bisphosphonates (IVBP) to determine
      whether a subset may be atypical fractures. METHODS: Between 2005 and 2010, we
      identified patients with known IVBP therapy for multiple myeloma or metastatic
      breast cancer, who subsequently sustained a femur fracture based on
      hospitalization, oncology, pharmacy and chemotherapy visit records. Radiographs
      were examined by an orthopedic surgeon to determine anatomic fracture site and
      pattern. An atypical fracture was defined as a transverse or short oblique
      fracture occurring below the lesser trochanter with evidence of focal hypertrophy
      of the lateral cortex and absence of biopsy-proven malignancy or radiation
      therapy at the fracture site. RESULTS: A total of 62 patients with breast cancer
      (N=39) or multiple myeloma (N=23) with femur fracture and prior IVBP treatment
      for bone malignancy were identified. There were 30 proximal hip, 18
      subtrochanteric and 14 femoral shaft fractures. Intraoperative bone samples were
      sent in 29 of 58 fracture cases undergoing operative repair, with 76% positive
      for malignancy. Six cases (4 breast cancer, 2 multiple myeloma) of atypical femur
      fracture were identified, two with negative intraoperative pathology and four
      with no bone biopsy samples sent. Five of the six patients with atypical fracture
      had bilateral femur findings, including two with transverse fracture in the
      contralateral femur and three with focal hypertrophy of the contralateral cortex.
      Two atypical fracture cases also experienced osteonecrosis of the jaw compared to
      3 in the remaining cohort (33% vs. 5%, p=0.07). Patients with atypical fracture
      received more IVBP (median 55 vs. 15 doses) and zoledronic acid (32 vs. 12 doses)
      and had longer treatment duration (median 5.9 vs. 1.6 years) compared to patients
      without atypical fracture (all p<=0.01). CONCLUSIONS: Among 62 patients who
      received IVBP for skeletal malignancy and experienced a femur fracture, we
      identified six cases of atypical fracture. While fractures in this population are
      often assumed to be pathologic, prospective studies investigating fracture
      pattern, microscopic bone pathology and pharmacologic exposures should be
      conducted to further examine the association of IVBP and atypical femur
      fractures.

PMID- 22634176
TI  - miR-155 modulates TNF-alpha-inhibited osteogenic differentiation by targeting
      SOCS1 expression.
AB  - Bone morphogenetic proteins (BMPs) can induce ectopic bone formation, which is
      negatively regulated by inflammatory cytokines, such as tumor necrosis factor
      (TNF)-alpha. Recently, miR-155 has been reported to regulate the transforming
      growth factor (TGF)-beta signaling pathway and inflammatory responses. However,
      whether and how miR-155 modulates TNF-alpha-regulated osteogenic differentiation
      have not been explored. In this study, we demonstrated that miR-155 was involved
      in TNF-alpha-mediated inhibition of osteogenic differentiation. Knockdown of miR
      155 partially mitigated the inhibition of TNF-alpha on BMP-2-induced osteogenic
      differentiation. Bioinformatic analysis identified the candidate target site in
      the 3' untranslated region (3'UTR) of SOCS1. Knockdown of miR-155 increased SOCS1
      protein expression during TNF-alpha stimulation in MC3T3-E1 cells. And
      transfection with miR-155 inhibited the wild-type, but not the mutant, 3'UTR of
      SOCS1-regulated luciferase activity, indicating that SOCS1 is a direct target of
      miR-155 in osteoblast cells. Furthermore, miR-155 expression could be induced by
      TNF-alpha through the JNK pathway. As the result of increased SOCS1 expression,
      knockdown of miR-155 significantly reduced the JNK/c-Jun activation. In addition,
      transfection of SOCS1 siRNA or overexpression of SOCS1 coding region could narrow
      the differences of alkaline phosphatase (ALP) and osteocalcin (OSC) expression
      between the control and miR-155 inhibitor transfected cells. These data indicated
      that miR-155 modulates TNF-alpha-regulated osteogenic differentiation by
      targeting SOCS1, at least partially through the SAPK/JNK pathway. These findings
      may provide new insights into understanding the regulatory role of miR-155 in the
      process of osteogenic differentiation in inflammatory condition.

PMID- 22634177
TI  - Alterations in the osteocyte lacunar-canalicular microenvironment due to estrogen
      deficiency.
AB  - While reduced estrogen levels have been shown to increase bone turnover and
      induce bone loss, there has been little analysis of the effects of diminished
      estrogen levels on the lacunar-canalicular porosity that houses the osteocytes.
      Alterations in the osteocyte lacunar-canalicular microenvironment may affect the
      osteocyte's ability to sense and translate mechanical signals, possibly
      contributing to bone degradation during osteoporosis. To investigate whether
      reduced estrogen levels affect the osteocyte microenvironment, this study used
      high-resolution microscopy techniques to assess the lacunar-canalicular
      microstructure in the rat ovariectomy (OVX) model of postmenopausal osteoporosis.
      Confocal microscopy analyses indicated that OVX rats had a larger effective
      lacunar-canalicular porosity surrounding osteocytes in both cortical and
      cancellous bone from the proximal tibial metaphysis, with little change in
      cortical bone from the diaphysis or cancellous bone from the epiphysis. The
      increase in the effective lacunar-canalicular porosity in the tibial metaphysis
      was not due to changes in osteocyte lacunar density, lacunar size, or the number
      of canaliculi per lacuna. Instead, the effective canalicular size measured using
      a small molecular weight tracer was larger in OVX rats compared to controls.
      Further analysis using scanning and transmission electron microscopy demonstrated
      that the larger effective canalicular size in the estrogen-deficient state was
      due to nanostructural matrix-mineral level differences like loose collagen
      surrounding osteocyte canaliculi. These matrix-mineral differences were also
      found in osteocyte lacunae in OVX, but the small surface changes did not
      significantly increase the effective lacunar size. The alterations in the lacunar
      canalicular surface mineral or matrix environment appear to make OVX bone tissue
      more permeable to small molecules, potentially altering interstitial fluid flow
      around osteocytes during mechanical loading.

PMID- 22634178
TI  - Effects of 17beta-estradiol on adiponectin regulation of the expression of
      osteoprotegerin and receptor activator of nuclear factor-kappaB ligand.
AB  - Adiponectin may exert a negative effect on bone metabolism by regulating
      osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand
      (RANKL) expression. However, the action of adiponectin on bone may be influenced
      by estrogen in women. The present study was undertaken to investigate the effects
      of 17beta-estradiol (E2) on adiponectin-regulated OPG and RANKL expression in
      human osteoblast. Human osteoblasts were treated with alpha-MEM containing
      10MUg/ml adiponectin alone or together with 10(-10) to 10(-8)M E2 for 12-48h.
      Cells were also treated with alpha-MEM containing 10MUg/ml adiponectin together
      with 10(-8)M E2 plus p38 agonist-anisomycin or estrogen receptor (ER) antagonist
      ICI182780 for 48h. The effects of E2 were also investigated by knockdown of ERs
      or overexpression of p38 MAPK in osteoblasts. Further, we examined the effects of
      E2 on adiponectin-dependent osteoclastogenesis by the co-culture systems of
      osteoblast and CD14+ peripheral blood monocytes (PBMCs). Real-time quantitative
      PCR (RT-PCR) and ELISA were used to detect OPG/RANKL mRNA and their corresponding
      protein expression, Western Blot was used to analyze the phosphorylated p38 (p
      p38) levels. The results showed that E2 blocked adiponectin-induced p38
      phosphorylation, decreased adiponectin-regulated OPG/RANKL mRNA and protein
      expression in a dose- and time-dependent manner. ICI182780 or knockdown of ERs
      abolished the effects of E2 on adiponectin-dependent p38 phosphorylation and
      OPG/RANKL expression. Furthermore, anisomycin or overexpression of p38 also
      reserved the effects of E2 on adiponectin-dependent p38 phosphorylation and
      OPG/RANKL expression. E2 inhibited adiponectin-dependent osteoclastogenesis in
      the co-culture systems of osteoblast and CD14+ PBMCs, whereas anisomycin,
      ICI182780, knockdown of ERs and overexpression of p38 significantly reversed this
      response. In conclusions, our findings demonstrated, through blocking the
      activation of adiponectin-induced p38 MAPK, E2 suppressed the adiponectin
      regulated OPG/RANKL expression and then inhibited osteoclastogenesis, which
      suggested that estrogen would suppress the effect of adiponectin on bone
      metabolism.

PMID- 22634179
TI  - A new toolkit for modeling RNA from a pseudo-torsional space: commentary on
      "discrete RNA libraries from pseudo-torsional space" by Humphris-Narayanan and
      Pyle (J. Mol. Biol. March 2012).

PMID- 22634181
TI  - High mobility group box 1 promotes small intestinal damage induced by
      nonsteroidal anti-inflammatory drugs through Toll-like receptor 4.
AB  - Release of high mobility group box 1 (HMGB1) from damaged cells, which is
      involved in many types of tissue injuries, activates inflammatory pathways by
      stimulating multiple receptors, including Toll-like receptor 2 (TLR2), TLR4, and
      receptor for advanced glycation end-products (RAGE). Our objective was to
      determine the role of HMGB1 in nonsteroidal anti-inflammatory drug (NSAID)
      induced damage of the small intestine. Oral indomethacin (10 mg/kg) induced
      damage to the small intestine and was associated with increases in intestinal
      HMGB1 expression and serum HMGB1 levels. In wild-type mice, recombinant human
      HMGB1 aggravated indomethacin-induced small intestinal damage; enhanced the mRNA
      expression levels of tumor necrosis factor alpha (TNF-alpha), monocyte
      chemotactic protein 1, and KC; activated nuclear factor kappa B; and stimulated
      phosphorylation of the mitogen-activated protein kinases p38, extracellular
      signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). In contrast,
      blocking HMGB1 action with neutralizing antibodies prevented damage and inhibited
      both inflammatory cytokine overexpression and activation of these intracellular
      signaling pathways. TLR2-knockout (KO) and RAGE-KO mice exhibited high
      sensitivities to indomethacin-induced damage, similar to wild-type mice, whereas
      TLR4-KO mice exhibited less severe intestinal damage and lower levels of TNF
      alpha mRNA expression. Exogenous HMGB1 aggravated the damage in TLR2- and RAGE-KO
      mice but did not affect the damage in TLR4-KO mice. Thus, our results suggest
      that HMGB1 promotes NSAID-induced small intestinal damage through TLR4-dependent
      signaling pathways.

PMID- 22634180
TI  - Elevated expression of Fn14 in non-small cell lung cancer correlates with
      activated EGFR and promotes tumor cell migration and invasion.
AB  - Lung cancer is the leading cause of cancer deaths worldwide; approximately 85% of
      these cancers are non-small cell lung cancer (NSCLC). Patients with NSCLC
      frequently have tumors harboring somatic mutations in the epidermal growth factor
      receptor (EGFR) gene that cause constitutive receptor activation. These patients
      have the best clinical response to EGFR tyrosine kinase inhibitors (TKIs).
      Herein, we show that fibroblast growth factor-inducible 14 (Fn14; TNFRSF12A) is
      frequently overexpressed in NSCLC tumors, and Fn14 levels correlate with p-EGFR
      expression. We also report that NSCLC cell lines that contain EGFR-activating
      mutations show high levels of Fn14 protein expression. EGFR TKI treatment of EGFR
      mutant HCC827 cells decreased Fn14 protein levels, whereas EGF stimulation of
      EGFR wild-type A549 cells transiently increased Fn14 expression. Furthermore,
      Fn14 is highly expressed in EGFR-mutant H1975 cells that also contain an EGFR TKI
      resistance mutation, and high TKI doses are necessary to reduce Fn14 levels.
      Constructs encoding EGFRs with activating mutations induced Fn14 expression when
      expressed in rat lung epithelial cells. We also report that short hairpin RNA
      mediated Fn14 knockdown reduced NSCLC cell migration and invasion in vitro.
      Finally, Fn14 overexpression enhanced NSCLC cell migration and invasion in vitro
      and increased experimental lung metastases in vivo. Thus, Fn14 may be a novel
      therapeutic target for patients with NSCLC, in particular for those with EGFR
      driven tumors who have either primary or acquired resistance to EGFR TKIs.

PMID- 22634183
TI  - The benefits of an infectious disease/radiology multidisciplinary team meeting.

PMID- 22634182
TI  - Concentration-dependent isoflurane effects on withdrawal reflexes in pigs and the
      role of the stimulation paradigm.
AB  - In this prospective two-phase experimental trial, 10 pigs were anaesthetized
      twice with isoflurane only. In the first phase, the individual minimum alveolar
      concentration (MAC) was determined and in the second phase the effects on
      withdrawal reflexes of increasing end-tidal isoflurane concentrations (from 1.6%
      to 2.8%) were assessed. Single, 10 and 60 repeated electrical stimulations were
      used to evoke withdrawal reflexes which were recorded and quantified by
      electromyography. Recruitment curves for reflex amplitude for increasing
      stimulation intensities and isoflurane concentrations were constructed.
      Isoflurane MAC was 1.9 +/- 0.3%. Reflexes evoked by repeated stimulation were
      suppressed at isoflurane concentrations significantly higher than those which
      suppressed complex movements during MAC determination (P=0.014 and P=0.006 for 10
      and 60 repeated stimuli respectively). Isoflurane up to 2.8% was still not able
      to abolish reflex activity evoked by repeated stimulations in all pigs. Single
      stimulation reflexes were suppressed at significantly lower concentrations than
      repeated stimulation reflexes (P=0.008 and P=0.004 for 10 and 60 repeated
      stimuli, respectively). Reflex amplitude was significantly correlated with
      isoflurane concentration (P<0.001, r=-0.85) independent of the individual MAC.
      The findings indicate that the level at which isoflurane suppresses withdrawal
      reflexes is dependent on the stimulation paradigm (single vs. repeated electrical
      stimulation), and there is limited value in expressing reflex withdrawal
      suppression in terms of MAC as purposeful and reflex movements are independently
      affected by isoflurane in individual animals.

PMID- 22634184
TI  - Vicriviroc plus optimized background therapy for treatment-experienced subjects
      with CCR5 HIV-1 infection: final results of two randomized phase III trials.
AB  - BACKGROUND: Vicriviroc, a novel HIV CCR5 antagonist, demonstrated significant
      efficacy and favorable tolerability in phase II trials in treatment-experienced
      subjects, supporting further evaluation in phase III studies. METHODS: Two
      identical double-blind, placebo (PBO)-controlled trials in CCR5-tropic HIV
      infected subjects with documented resistance to two antiretroviral classes were
      conducted. Subjects were randomized to vicriviroc 30 mg QD (N = 571) or PBO (N =
      286) with open-label optimized background therapy (OBT) containing >=2 fully
      active antiretroviral drugs. The primary endpoint was percentage of subjects with
      <50 copies/mL HIV RNA at 48 weeks. It was analyzed in a logistic regression with
      treatment (vicriviroc + OBT/PBO + OBT), use of enfuvirtide in baseline OBT
      (yes/no), and baseline HIV RNA (<=100,000/>100,000 copies/mL) as covariates. In
      addition, a pre-planned analysis to examine other efficacy and safety endpoints
      was conducted. RESULTS: Baseline characteristics of the pooled mITT population
      (vicriviroc, n = 486; PBO, n = 235) included mean HIV RNA of 4.6 log(10)
      copies/mL and mean CD4 count of 257 cells/MUL. Approximately 60% of subjects
      received >=3 active drugs in the OBT. The percentage of subjects with <50
      copies/mL HIV RNA was not significantly different between vicriviroc and PBO at
      week 48 (64% vs 62%, p = 0.6). However, in subjects receiving <=2 active drugs in
      their OBT, the proportion achieving <50 copies/mL HIV RNA was higher in those
      receiving vicriviroc compared with PBO (70% vs 55%, p = 0.02). CONCLUSIONS: The
      studies failed to show significant efficacy gains when vicriviroc was added to
      OBT. However, given the efficacy results of earlier vicriviroc trials and other
      CCR5 antagonist, studies are needed to define the role of this class of drugs in
      the treatment of HIV. Clinical trial identifier: http://www.clinicaltrial.gov/:
      VICTOR-E3 (NCT00523211) and VICTOR-E4 (NCT00474370).

PMID- 22634185
TI  - IQGAP1 regulates hyaluronan-mediated fibroblast motility and proliferation.
AB  - IQGAP1, an essential scaffolding protein, forms a complex with the hyaluronan
      receptor CD44. In this study, we have examined the importance of IQGAP1 for
      hyaluronan-mediated fibroblast migration and proliferation. Hyaluronan induced
      formation of F-actin fibers and focal adhesions, which was dependent on IQGAP1.
      IQGAP1 was required for hyaluronan- but not for platelet-derived growth factor
      (PDGF)-BB-induced cell migration, and was required for both hyaluronan- and PDGF
      BB-mediated fibroblast proliferation, but not for proliferation induced by 10%
      fetal bovine serum. Depletion of IQGAP1 suppressed hyaluronan-induced activation
      of Rac1 and enhanced the activation of RhoA. Taken together, these findings
      indicate important roles for IQGAP1 in hyaluronan-stimulated migration and
      proliferation of fibroblasts.

PMID- 22634186
TI  - Structural characterization of the PliG lysozyme inhibitor family.
AB  - Several Gram-negative bacteria protect themselves against the lytic action of
      host lysozymes by producing specific proteinaceous inhibitors. So far, four
      different families of lysozyme inhibitors have been identified including Ivy
      (Inhibitor of vertebrate lysozyme), MliC/PliC (Membrane associated/periplasmic
      inhibitor of C-type lysozyme), PliI and PliG (periplasmic inhibitors of I- and G
      type lysozymes, respectively). Here we provide the first crystallographic
      description of the PliG family. Crystal structures were obtained for the PliG
      homologues from Escherichia coli, Salmonella enterica serotype Typhimurium and
      Aeromonas hydrophila. These structures show that the fold of the PliG family is
      very distinct from that of all other families of lysozyme inhibitors. Small-angle
      X-ray scattering studies reveal that PliG is monomeric in solution as opposed to
      the dimeric PliC and PliI. The PliG family shares a highly conserved SG(x)xY
      sequence motif with the MliC/PliC and PliI families where it was shown to reside
      on a loop that blocks the active site of lysozyme leading to inhibition.
      Surprisingly, we found that in PliG this motif is not well exposed and not
      involved in the inhibitory action. Instead, we could identify a distinct cluster
      of surface residues that are conserved across the PliG family and are essential
      for efficient G-type lysozyme inhibition, as evidenced by mutagenesis studies.

PMID- 22634188
TI  - A low error reconstruction method for confocal holography to determine 3
      dimensional properties.
AB  - A confocal holography microscope developed at the University of Victoria uniquely
      combines holography with a scanning confocal microscope to non-intrusively
      measure fluid temperatures in three-dimensions (Herring, 1997, Abe and Iwasaki,
      1999, Jacquemin et al., 2005). The Confocal Scanning Laser Holography (CSLH)
      microscope was built and tested to verify the concept of 3D temperature
      reconstruction from scanned holograms. The CSLH microscope used a focused laser
      to non-intrusively probe a heated fluid specimen. The focused beam probed the
      specimen instead of a collimated beam in order to obtain different phase-shift
      data for each scan position. A collimated beam produced the same information for
      scanning along the optical propagation z-axis. No rotational scanning mechanisms
      were used in the CSLH microscope which restricted the scan angle to the cone
      angle of the probe beam. Limited viewing angle scanning from a single view point
      window produced a challenge for tomographic 3D reconstruction. The reconstruction
      matrices were either singular or ill-conditioned making reconstruction with
      significant error or impossible. Establishing boundary conditions with a
      particular scanning geometry resulted in a method of reconstruction with low
      error referred to as "wily". The wily reconstruction method can be applied to
      microscopy situations requiring 3D imaging where there is a single viewpoint
      window, a probe beam with high numerical aperture, and specified boundary
      conditions for the specimen. The issues and progress of the wily algorithm for
      the CSLH microscope are reported herein.

PMID- 22634189
TI  - Effect of time of consumption of preloads on measures of satiety in healthy
      normal weight women.
AB  - Differences in the time interval between preload and test meal may account for
      the variation in the satiating effects of whey protein found in previous preload
      studies. The objective was to compare the satiating effects (ad libitum meal
      intake at a set time after ingestion of preload) of whey protein (including
      glycomacropeptide) and maltodextrin carbohydrate and to determine whether such
      effects were influenced by the timing of preloads. On nine separate days, 19
      healthy normal weight women consumed mixed composition preloads containing either
      water, or maltodextrin, or whey protein, 30, 60 or 120 min before an ad libitum
      test meal. Whey protein reduced food intake (p < 0.05) at the test meal more than
      maltodextrin and water (respective food energy intakes were 2343, 2584 and 3135
      kJ). The time interval between preload and test meal did not affect the food
      intake response. Total energy intake (preload+test meal) differed, with intake
      for the maltodextrin-enriched preload being greater than that for the whey
      protein-enriched preload, which was greater than for the water control. Total
      respective energy intakes were 3955, 3676 and 3135 kJ. Subjective ratings of
      appetite did not support a greater satiating effect of whey protein versus
      maltodextrin on food intake but there was evidence for a satiating effect of
      maltodextrin and whey protein versus the water control.

PMID- 22634187
TI  - Non-viral gene therapy for spinal cord regeneration.
AB  - Spinal cord injury (SCI) normally results in life-long disabilities and a broad
      range of secondary complications. Advances in therapeutic delivery during the
      past few decades offer hope for such victims. However, the limited functional
      improvement shown in in vivo studies hinders effective therapeutic application in
      clinical practice. Recent studies showed that gene vectors can transfect cells
      present in the lesion of an injured spinal cord (endogenous cells) and thereby
      produce therapeutic molecules with long-lasting biological effects that promote
      neural tissue regeneration. In this article we review recent advances in non
      viral gene delivery into neural cells and their use for gene therapy in SCI.

PMID- 22634190
TI  - How to improve the promotion of Korean beef barbecue, bulgogi, for international
      customers. An application of quality function deployment.
AB  - Quality function deployment (QFD) is a product development technique that
      translates customer requirements into activities for the development of products
      and services. This study utilizes QFD to identify American customer's
      requirements for bulgogi, a popular Korean dish among international customers,
      and how to fulfill those requirements. A customer survey and an expert opinion
      survey were conducted for US customers. The top five customer requirements for
      bulgogi were identified as taste, freshness, flavor, tenderness, and juiciness;
      ease of purchase was included in the place of tenderness after calculating the
      weight requirements. Eighteen engineering characteristics were developed, and a
      'localization of bulgogi menu' is strongly related to the other characteristics
      as well. The results from the calculation of relative importance of engineering
      characteristics identified that the 'control of marinating time', 'localization
      of bulgogi menu', 'improvement of cooking and serving process', 'development of
      recipe by parts of beef', and 'use of various seasonings' were the highest
      contributors to the overall improvement of bulgogi. The relative importance of
      engineering characteristics, correlation, and technical difficulties are ranked
      and integrated to develop the most effective strategy. The findings are discussed
      relative to industry implications.

PMID- 22634191
TI  - Ion-exclusion chromatography determination of organic acid in uridine 5'
      monophosphate fermentation broth.
AB  - Simultaneous determination of organic acids using ion-exclusion liquid
      chromatography and ultraviolet detection is described. The chromatographic
      conditions are optimized when an Aminex HPX-87H column (300 * 7.8 mm) is
      employed, with a solution of 3 mmol/L sulfuric acid as eluent, a flow rate of 0.4
      mL/min and a column temperature of 60 degrees C. Eight organic acids (including
      orotic acid, alpha-ketoglutaric acid, citric acid, pyruvic acid, malic acid,
      succinic acid, lactic acid and acetic acid) and one nucleotide are successfully
      quantified. The calibration curves for these analytes are linear, with
      correlation coefficients exceeding 0.999. The average recovery of organic acids
      is in the range of 97.6% ~ 103.1%, and the relative standard deviation is in the
      range of 0.037% ~ 0.38%. The method is subsequently applied to obtain organic
      acid profiles of uridine 5'-monophosphate culture broth fermented from orotic
      acid by Saccharomyces cerevisiae. These data demonstrate the quantitative
      accuracy for nucleotide fermentation mixtures, and suggest that the method may
      also be applicable to other biological samples.

PMID- 22634192
TI  - Separation and evaluation of soybean protein hydrolysates prepared by immobilized
      metal ion affinity chromatography with different metal ions.
AB  - Metal ion affinity chromatography is widely used to purify peptides on the basis
      of the dissimilarities of their amino acids. However, researchers are interested
      in the separation differences between different metal ions in this method. In our
      study, four kinds of commonly used metal ions are compared by the amount of
      immobilized metal ion on iminodiacetic acid-Sepharose and binding amount of
      soybean peptide to immobilized iminodiacetic acid-Mn(+) adsorbents and evaluated
      by high-performance liquid chromatography (HPLC) profiles. The results show that
      due to the different adsorption behaviors of metal ions, the binding ability
      order of soybean protein peptide on the column should be Fe(3+) > Cu(2+) > Zn(2+)
      > Ca(2+). The HPLC profiles show that peptides adsorbed by four kinds of metal
      ions display similar strong hydrophobic characteristics.

PMID- 22634193
TI  - Evaluation of simulant migration of volatile nitrosamines from latex gloves and
      balloons by HS-SPME-GC-MS.
AB  - Nitrosamines are a group of carcinogens that have been found in various latex
      products. Methods have been developed for extraction, concentration and detection
      of simulant migration of volatile nitrosamines from latex gloves and balloons.
      After glove samples or balloon samples were treated with artificial sweat and
      artificial saliva, headspace solid-phase microextraction and gas chromatography
      with mass spectrometer detection were performed. Eight volatile nitrosamines were
      extracted by a fused silica fiber coated with carboxen-polydimethylsioxane, and
      solid-phase microextraction conditions were optimized. The developed method was
      successfully used to analyze simulant migration of volatile nitrosamines from
      latex gloves and balloons. The described methods are rapid and simple, with
      adequate sensitivity and without organic solvent.

PMID- 22634194
TI  - Eating on the run. A qualitative study of health agency and eating behaviors
      among fast food employees.
AB  - Understanding the relationship between obesity and fast food consumption
      encompasses a broad range of individual level and environmental factors. One
      theoretical approach, the health capability framework, focuses on the complex set
      of conditions allowing individuals to be healthy. This qualitative study aimed to
      identify factors that influence individual level health agency with respect to
      healthy eating choices in uniformly constrained environments (e.g., fast food
      restaurants). We used an inductive qualitative research design to develop an
      interview guide, conduct open-ended interviews with a purposive sample of 14
      student fast food workers (aged 18-25), and analyze the data. Data analysis was
      conducted iteratively during the study with multiple coders to identify themes.
      Emergent themes included environmental influences on eating behaviors (time,
      cost, restaurant policies, social networks) and internal psychological factors
      (feelings associated with hunger, food knowledge versus food preparation know
      how, reaction to physical experiences, perceptions of food options, delayed
      gratification, and radical subjectivity). A localized, embedded approach to
      analyzing the factors driving the obesity epidemic is needed. Addressing
      contextual interactions between internal psychological and external environmental
      factors responds to social justice and public health concerns, and may yield more
      relevant and effective interventions for vulnerable communities.

PMID- 22634195
TI  - Resemblance of dietary intakes of snacks, sweets, fruit, and vegetables among
      mother-child dyads from low income families.
AB  - The objective of this study was to determine the correlation between intake of
      snacks, sweets, fruit, vegetables, and energy in low-income mother-child dyads.
      This was a secondary analysis of data collected from Head Start centers in
      Houston, Texas and Birmingham, Alabama. Twenty four hour dietary recalls for one
      weekend day were collected from mother (mean 31.8 yrs [range: 20.1-72.4 yrs])
      child (mean 4.4 yrs [range 2.8-5.8 yrs]) dyads (N=650). Means+/-SD were
      calculated for intake of food categories and energy. Pearson's partial
      correlation coefficients were used to detect associations between the intakes of
      the dyads. Main outcome measures were the correlations between the intake of
      snacks, sweets, fruit, vegetables, and energy in the mother-child dyads. Partial
      correlations showed that children's intake of snacks, sweets, fruit, vegetables,
      and energy were all correlated with the mother's intake of these foods/energy
      (all p<0.001). Children's intake of fruit was correlated with the mother's intake
      of vegetables (p<0.001); children's energy intake was correlated with mother's
      intake of sweets, fruit, and vegetables (all p<0.001). It is important that food
      and nutrition professionals provide the guidance needed that encourages intake of
      nutrient-dense snacks and fruit and vegetables in mothers so they can model
      healthier food consumption behaviors for their children.

PMID- 22634196
TI  - Overweight/obesity is associated with food choices related to rice and beans,
      colors of salads, and portion size among consumers at a restaurant serving buffet
      by-weight in Brazil.
AB  - The present study investigated the prevalence of overweight/obesity and its
      relationship with behavioral and food choice characteristics among consumers at a
      restaurant serving buffet-by-weight in the city of Florianopolis, southern
      Brazil, during lunch time. An analytical cross-sectional survey of 675 consumers
      aged 16-81 years was conducted. The measures included anthropometric, socio
      demographic, and behavioral characteristics, as well as portion size and a
      photographic record of the plate chosen by the consumer. The results indicated a
      prevalence of overweight/obesity in the sample of 33.8%. Overall, after an
      adjustment for other variables (sex, age, schooling, marital status, and food
      choice variables), overweight/obesity was positively associated with not choosing
      rice and beans (PR=1.11) and larger portion sizes (PR=1.08 for a portion size of
      347-462 g and PR=1.16 for a portion size of 463 g or more). Moreover, choosing 1
      2 colors of salads showed a positive association when compared with choosing 3 or
      more colors of salads (PR=1.06). Efforts in helping consumers make healthier food
      choices when eating out and thereby possibly reduce weight gain should address
      those aspects along with socio-demographic factors.

PMID- 22634197
TI  - Capsaicinoids and capsinoids. A potential role for weight management? A
      systematic review of the evidence.
AB  - Capsaicinoids are a group of chemicals found in chilli peppers, with bioactive
      properties. The purpose of this study is to systematically review research
      investigating the potential benefits capsaicinoid compounds may have in relation
      to weight management. Medical databases were searched and 90 trials found, 20 of
      which were selected for inclusion, involving 563 participants. Three main areas
      of potential benefit for weight management were found: (1) increased energy
      expenditure; (2) increased lipid oxidation and (3) reduced appetite. Trial
      duration, dosage and sized varied, though trials were generally of high quality
      with a low risk of bias. It was observed that consumption of capsaicinoids
      increases energy expenditure by approximately 50 kcal/day, and that this would
      produce clinically significant levels of weight loss in 1-2 years. It was also
      observed that regular consumption significantly reduced abdominal adipose tissue
      levels and reduced appetite and energy intake. The mechanism of action is not
      presently fully understood, although it is well accepted much of the effects are
      caused by stimulation of the TRPV1 receptor. While capsaicinoids are not a magic
      bullet for weight loss, the evidence is that they could play a beneficial role,
      as part of a weight management program.

PMID- 22634198
TI  - Children's coping after psychological stress. Choices among food, physical
      activity, and television.
AB  - Children's stress-coping behaviors and their determinants have not been widely
      studied. Some children eat more after stress and dietary restraint moderates
      stress eating in youth, but eating has been studied in isolation of other coping
      behaviors. Children may not choose to eat when stressed if other behavioral
      alternatives are available. The purpose was to determine individual difference
      factors that moderate the duration of stress coping choices and to determine if
      stress-induced eating in youth persists when other stress coping behaviors are
      available. Thirty children (8-12 years) completed a speech stressor on one day
      and read magazines on another day. They completed a free-choice period with
      access to food, TV, and physical activity on both days. Dietary restraint
      moderated changes in time spent eating and energy consumed from the control to
      stress day. Children high in restraint increased their energy intake on the
      stress day. Changes in the time spent watching TV were moderated by usual TV
      time, as children higher in usual TV increased their TV time after stress. Thus,
      dietary restrained children eat more when stressed when other common stress
      coping behaviors are freely available. These results extend the external validity
      of laboratory studies of stress-induced eating.

PMID- 22634199
TI  - Obesity and risk taking. A male phenomenon.
AB  - There is a growing tendency to regard overeating as an addiction, with obesity as
      its primary symptom. We propose that similar to other addictions, obesity is
      associated with excessive risk-taking in men, though not in women. To examine
      this suggestion we conducted two studies, one involving a sample of overweight
      and normal-weight students, and the other involving obese adults drawn from a
      dataset of health care clients, and a control sample of normal-weight adults. In
      both of these studies, we found that overweight and obese men took more risk in a
      laboratory task than normal-weight men, while overweight and obese women did not
      differ from normal-weight women in this respect. At the same time, obese women
      (but not overweight women) displayed higher impulsivity levels than normal-weight
      women. These findings shed light on the cognitive characteristics of obesity in
      men, and accent the importance of taking gender into account when developing
      research paradigms and treatment methods for obesity.

PMID- 22634200
TI  - Testing the Protein Leverage Hypothesis in a free-living human population.
AB  - The Protein Leverage Hypothesis (PLH) predicts that humans prioritize protein
      when regulating food intake. We tested a central prediction of PLH: protein
      intake will remain more constant than fat or carbohydrate in the face of dietary
      changes in a free-living population. Data come from a large sample of adult
      Filipino women participating in the Cebu Longitudinal Health and Nutrition Survey
      (CLHNS) located in Philippines. Longitudinal data analysis showed that, as
      predicted, calories of dietary protein remained more constant over time than
      calories of dietary carbohydrates or fat, even if corrected for the low
      proportional contribution of protein to dietary energy.

PMID- 22634201
TI  - Influences of packaging attributes on consumer purchase decisions for fresh
      produce.
AB  - Packaging attributes are considered to have an influence on consumer purchase
      decisions for food and, as a consequence, also on its consumption. To improve the
      current minimal understanding of these influences for fresh produce, a survey
      instrument in the form of an online questionnaire has been developed and launched
      in the US. The first part of the questionnaire covers consumers' preferences for
      packaging convenience features, characteristics, materials, disposal method, and
      others for fresh produces in general, and the second focuses on attributes like
      price, container size, produce shelf life for a specific fresh produce, sweet
      cherries, to allow us to supply specific values for these factors to the
      participants. Cluster and conjoint analyses of responses from 292 participants
      reveal that specific packaging and produce attributes affect consumer purchase
      decisions of fresh produce in general and of sweet cherries in particular (P <=
      0.05) and that some are population segment dependent (P <= 0.05). For produce
      packaging in general, 'extend the "best by" date' was ranked as the top
      convenience feature, the type of packaging material was considered to affect the
      food product quality (92.7%) and containers made from bio-based materials were
      highly appealing (3.52 out of 5.00). The most important attributes that affect
      the purchasing decisions of consumers regarding a specific fresh produce like
      sweet cherries are price (25%), shelf life (19%) and container size (17.2%).

PMID- 22634202
TI  - Ethno-veterinary survey of medicinal plants in Ruoergai region, Sichuan province,
      China.
AB  - AIM OF STUDY: In this study we aimed to survey and investigate the medicinal
      plants which are used to treat the veterinary diseases in Ruoergai region,
      Sichuan province, China. Meanwhile, the important medicinal plants were collected
      and identified for the further study. MATERIALS AND METHODS: Twenty folk
      veterinary practitioners from 8 township animal husbandry and veterinary stations
      in Ruoergai region were investigated and interviewed. The important local
      medicinal materials, including plants, animals and mineral drugs, were collected
      by scientific methods and identified by the pharmacognosist of Lanzhou
      University, China. RESULTS: According to the investigation, only 20 folk
      veterinary practitioners still used 129 species of traditional medicine to treat
      the livestock's diseases. In these medicine, 93 species were native and
      Ranunculaceae (12, 12.90%), Compositae (11, 11.83%), Papaveraceae (7, 7.53%) were
      the predominant families. At the same time, herbs (36.56%) are the most widely
      used part of plant, and respiratory diseases (21.02%) and gastrointestinal
      diseases (19.89%) were the main animal's diseases in this region. CONCLUSION:
      Ethno-veterinary medicine made an extraordinary contribution to the sound
      development of animal husbandry in Ruoergai. But the inherit, protect and
      development should be paid more attentions in the future, and the species which
      have not been studied should be developed priority to find biological activities
      and new bioactive compounds further.

PMID- 22634203
TI  - Evaluation of naturally occurring curcuminoids and related compounds against
      mosquito larvae.
AB  - The three curcuminoid components commonly isolated from Curcuma longa, curcumin
      (1), demethoxycurcumin (2), and bis-demethoxycurcumin (3) were separated and
      isolated from a commercially available turmeric extract product in high purity
      and sufficient amounts. Three more derivatives of curcumin, the di-O
      demethylcurcumin (4), di-O-methylcurcumin (5) and the di-O-acetylcurcumin (6)
      were also synthesized and characterized. All six compounds were evaluated for
      their larvicidal effect against the mosquito Culex pipiens. Curcumin (1)
      exhibited highly potent larvicidal activity with LC(50) value of 19.07mgL(-1).
      Moreover, di-O-demethylcurcumin (4), was found to be equally active with LC(50)
      value of 12.42mgL(-1). Based on the LC(90) values of the two compounds, di-O
      demethylcurcumin (4) was the most active of all, resulting in an LC(90) value of
      29.40mgL(-1), almost half of the LC(90) value 61.63mgL(-1) found for compound 1.
      The rest of the compounds were inactive at concentrations even as high as 150mgL(
      1) indicating a dependence of the larvicidal activity upon the substitution
      patent and the presence of aromatic hydroxyl and methoxy moieties. These results
      show for the first time the potential of this valuable natural product regarding
      its use as vector control agent.

PMID- 22634204
TI  - After five years of chemical control: colonies of the triatomine Eratyrus
      mucronatus are still present in Bolivia.
AB  - Chagas disease, which is caused by the parasite Trypanosoma cruzi, is transmitted
      to humans by blood-sucking bugs (Triatominae). Eratyrus mucronatus is a well
      dispersed triatomine species, found sometimes in dwellings. In the Apolo region
      of Bolivia, people continue to complain of bites by this bug despite five years
      of chemical control. For the first time, the domiciliation process of E.
      mucronatus was evaluated in a zone treated by insecticide, and it was compared
      with a previous situation 14 years ago. Both an entomological and a serological
      study were carried out: 152 dwellings were visited and 491 blood samples were
      analyzed with Stat-Pack and ELISA tests. In 34 dwellings (23% of the total
      visited dwellings), 160 triatomines of all stages were collected belonging to two
      species, E. mucronatus (98% of the capture) and Panstrongylus geniculatus. A
      domiciliation of E. mucronatus is demonstrated, particularly in the peridomicile.
      Bugs were captured more frequently in bedrooms in the intradomicile, and in
      curahuas (boundary walls in rammed mud) in the peridomicile. A P. geniculatus
      adult was found infected with T. cruzi. No evidence of a local vectorial
      transmission was found. In particular, the limited effect of the insecticide on
      the presence of E. mucronatus and the role of the curahuas as a source of
      intrusion/domiciliation process are discussed.

PMID- 22634205
TI  - A retrospective study on burden of human echinococcosis based on Hospital
      Discharge Records from 2001 to 2009 in Sardinia, Italy.
AB  - Cystic Echinococcosis (CE) is an infective zoonosis that represents a worldwide
      important public health problem. In humans, its manifestations may range from
      asymptomatic infection to severe disease and possible death, and lead to economic
      losses from treatment costs and lost wages. Recent studies suggest that this
      disease has a large social impact in endemic areas, and estimates of burden in
      terms of monetary and no-monetary impact on human health are essential to
      allocate financial and technical resources. In Sardinia, the most affected
      Italian region per number of inhabitants, CE is still endemic, although three
      eradication campaigns have been carried out in 1962, 1978, and 1987,
      respectively. To date, the burden of human CE in Sardinia remains poorly defined.
      In this work, a retrospective study was carried out using public Hospital
      Discharge Records spanning from 2001 to 2009. During these years, a total of 1409
      discharges were recorded: 1196 (84.88%) records corresponding to patients
      hospitalized for symptoms directly correlated to CE (primary diagnosis), and 213
      (15.11%) records corresponding to patients hospitalized for symptoms not directly
      correlated to CE and with an afterwards or concurrent diagnosis of echinococcosis
      made during the hospitalization (secondary diagnosis). The annual regional
      average record (discharge rate) was 9.3/100,000 inhabitants. Direct cost
      associated with diagnosis, surgery or chemotherapy, medical care, and
      hospitalization in humans were evaluated in this work. Furthermore, burden of
      disease was also evaluated by using the disability-adjusted life years (DALYs),
      the preferred disease-burden measure of the World Health Organization. Knowing
      the burden of human CE in Sardinia is extremely important to enable the
      prioritization of control measures for this preventable neglected disease. This
      is the first study describing the measure of the overall disease burden in an
      Italian region endemic for this disease, performed by calculating the number of
      CE patients from Hospital Discharge Records.

PMID- 22634206
TI  - HIV evolution and progression of the infection to AIDS.
AB  - In this paper, we propose and discuss a possible mechanism, which, via continuous
      mutations and evolution, eventually enables HIV to break from immune control. In
      order to investigate this mechanism, we employ a simple mathematical model, which
      describes the relationship between evolving HIV and the specific CTL response and
      explicitly takes into consideration the role of CD4(+)T cells (helper T cells) in
      the activation of the CTL response. Based on the assumption that HIV evolves
      towards higher replication rates, we quantitatively analyze the dynamical
      properties of this model. The model exhibits the existence of two thresholds,
      defined as the immune activation threshold and the immunodeficiency threshold,
      which are critical for the activation and persistence of the specific cell
      mediated immune response: the specific CTL response can be established and is
      able to effectively control an infection when the virus replication rate is
      between these two thresholds. If the replication rate is below the immune
      activation threshold, then the specific immune response cannot be reliably
      established due to the shortage of antigen-presenting cells. Besides, the
      specific immune response cannot be established when the virus replication rate is
      above the immunodeficiency threshold due to low levels of CD4(+)T cells. The
      latter case implies the collapse of the immune system and beginning of AIDS. The
      interval between these two thresholds roughly corresponds to the asymptomatic
      stage of HIV infection. The model shows that the duration of the asymptomatic
      stage and progression of the disease are very sensitive to variations in the
      model parameters. In particularly, the rate of production of the naive
      lymphocytes appears to be crucial.

PMID- 22634207
TI  - Leaving the loners alone: evolution of cooperation in the presence of antisocial
      punishment.
AB  - The idea that voluntary participation may promote the evolution of cooperation
      and punishment in public good games has been recently called into question based
      on the study of the complete strategy set in which anyone can punish anyone else.
      If punishment actions are detached from contribution and participation in the
      game, the combination of punishment and voluntary participation no longer leads
      to high levels of cooperation. We show that this result crucially depends on
      specific details of the role of those who abstain from the collective endeavour,
      and only holds for a small subset of assumptions. If these loners are truly
      alone, cooperators who punish only defectors prevail, even when antisocial
      punishment is available.

PMID- 22634208
TI  - Effects of aging and genotype on circadian rhythms, sleep, and clock gene
      expression in APPxPS1 knock-in mice, a model for Alzheimer's disease.
AB  - Profound disruptions of circadian rhythms and sleep/wake cycles constitute a
      major cause of institutionalization of AD patients. This study investigated
      whether a rodent model of AD, APP(NLH/NLH)/PS-1(P264L/264L) (APPxPS1) mice,
      exhibits circadian alterations. The APPxPS1 mice were generated using CD-1/129
      mice and Cre-lox knock-in technology to "humanize" the mouse amyloid (A)beta
      sequence and create a presenilin-1 mutation identified in familial early-onset AD
      patients. APPxPS1 and WT mice of several ages (~4, 11, and 15 months) were
      monitored for circadian rhythms in wheel running, cage activity, and sleep:wake
      behavior. After rhythm assessment, the mice were euthanized at zeitgeber time
      (ZT) 2 or 10 (i.e., 2 or 10 h after lights-on) and brains were dissected.
      Amyloidbeta levels were measured in cortical samples and brain sections of the
      hypothalamus and hippocampus were prepared and used for in situ hybridization of
      circadian or neuropeptide genes. The most significant effects of the APPxPS1
      transgenes were phase delays of ~2 h in the onset of daytime wakefulness bouts
      (P<0.005) and peak wakefulness (P<0.02), potentially relevant to phase delays
      previously reported in AD patients. However, genotype did not affect the major
      activity peaks or phases of wheel running, wake, or general movement, which were
      bimodal with dominant dawn and dusk activity. Expression of Period 2 in the
      suprachiasmatic nucleus was affected by ZT (P<0.0001) with a marginal interaction
      effect of age, genotype, and ZT (P<0.08). A separate analysis of the old animals
      indicated a robust interaction between ZT and genotype, as well as main effects
      of these parameters. Aging also altered sleep (e.g., bout length and amount of
      daytime sleep) and the amount of wheel running and cage activity. In conclusion,
      the APPxPS1 knock-in mice exhibit some alterations in their sleep:wake rhythm and
      clock gene expression, but do not show robust, genotype-related changes in
      activity rhythms. The prominent daytime activity peaks shown by the background
      strain complicate the use of these APPxPS1 knock-in mice for investigations of
      circadian activity rhythms in AD. In addition to this unusual activity pattern,
      lack of hyperactivity differentiates the APPxPS1 knock-in mice from other
      transgenic AD models.

PMID- 22634210
TI  - Neural precursors (NPCs) from adult L967Q mice display early commitment to "in
      vitro" neuronal differentiation and hyperexcitability.
AB  - The pathogenic factors leading to selective degeneration of motoneurons in ALS
      are not yet understood. However, altered functionality of voltage-dependent Na(+)
      channels may play a role since cortical hyperexcitability was described in ALS
      patients and riluzole, the only drug approved to treat ALS, seems to decrease
      glutamate release via blockade or inactivation of voltage-dependent Na(+)
      channels. The wobbler mouse, a murine model of motoneuron degeneration, shares
      some of the clinical features of human ALS. At early stages of the wobbler
      disease, increased cortical hyperexcitability was observed. Moreover, riluzole
      reduced motoneuron loss and muscular atrophy in treated wobbler mice. Here, we
      focussed our attention on specific electrophysiological properties, like voltage
      activated Na(+) currents and underlying regenerative electrical activity, as read
      outs of the neuronal maturation process of neural stem/progenitor cells (NPCs)
      isolated from the subventricular zone (SVZ) of adult early symptomatic wobbler
      mice. In self-renewal conditions, the rate of wobbler NPC proliferation "in
      vitro" was 30% lower than that of healthy mice. Conversely, the number of wobbler
      NPCs displaying early neuronal commitment and action potentials was significantly
      higher. Upon switching from proliferative to differentiative conditions, NPCs
      underwent significant changes in the key properties of voltage gated Na(+)
      currents. The most notable finding, in cells with neuronal morphology, was an
      increase in Na(+) current density that strictly correlated with an increased
      probability to generate action potentials. This feature was remarkably more
      pronounced in neurons differentiated from wobbler NPCs that upon sustained
      stimulation, displayed short trains of pathological facilitation. In agreement
      with this result, an increase in the number of c-Fos positive cells, a surrogate
      marker of neuronal network activation, was observed in the mesial cortex of the
      wobbler mice "in situ". Thus these findings, all together, suggest that a state
      of early neuronal hyperexcitability may be a major contributor of motoneuron
      vulnerability.

PMID- 22634211
TI  - Greater axial trough obliquity increases the risk of graft extrusion in lateral
      meniscus allograft transplantation.
AB  - BACKGROUND: In lateral meniscus allograft transplantation (MAT) using the keyhole
      method, precise trough drilling is critical for ensuring the graft is placed at
      the correct anatomic position to minimize the risk of extrusion. However, no
      study has focused on the effect of bony trough axial obliquity on graft
      extrusion. Our purpose was to investigate whether bony trough axial obliquity and
      bony trough position correlate with graft extrusion in lateral MAT using the
      keyhole method. HYPOTHESIS: We hypothesized that drilling the tibial bony trough
      at a greater axial angle would increase the risk of graft extrusion. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: The study involved 49
      patients who underwent lateral MAT between 2009 and 2010 following total or
      subtotal meniscectomy. The mean patient age at the time of surgery was 34 years
      (range, 19-52 years). Graft extrusion and bony trough parameters (absolute and
      relative distance at the anterior, center, and posterior cuttings of the bony
      trough, and axial trough angle [ATA]) were assessed using conventional magnetic
      resonance imaging (MRI) performed on postoperative day 2. The correlation between
      graft extrusion and MRI trough parameters was analyzed, and multiple linear
      regression analysis was performed to identify predictors of graft extrusion.
      RESULTS: Of the 7 MRI measurement parameters, the ATA (r = .355, P = .012),
      absolute anterior distance (r = .301, P = .031), and relative anterior distance
      (r = .307, P = .032) were found to positively correlate with absolute extrusion.
      The ATA (r = .296, P = .037) and relative anterior distance (r = .296, P = .039)
      were also found to correlate with relative extrusion. The ATA was found to be a
      predictor of absolute extrusion (beta = .36, P = .012) and relative extrusion
      (beta = .33, P = .019). CONCLUSION: The risk of graft extrusion increases as the
      axial plane trough angle increases. The angle can be reduced by ensuring that the
      bony trough starting point is not created in too lateral a position.

PMID- 22634209
TI  - Identification of radial glia-like cells in the adult mouse olfactory bulb.
AB  - Immature neurons migrate tangentially within the rostral migratory stream (RMS)
      to the adult olfactory bulb (OB), then radially to their final positions as
      granule and periglomerular neurons; the controls over this transition are not
      well understood. Using adult transgenic mice with the human GFAP promoter driving
      expression of enhanced GFP, we identified a population of radial glia-like cells
      that we term adult olfactory radial glia-like cells (AORGs). AORGs have large,
      round somas and simple, radially oriented processes. Confocal reconstructions
      indicate that AORGs variably express typical radial glial markers, only rarely
      express mouse GFAP, and do not express astroglial, oligodendroglial, neuronal, or
      tanycyte markers. Electron microscopy provides further supporting evidence that
      AORGs are not immature neurons. Developmental analyses indicate that AORGs are
      present as early as P1, and are generated through adulthood. Tracing studies show
      that AORGs are not born in the SVZa, suggesting that they are born either in the
      RMS or the OB. Migrating immature neurons from the adult SVZa are closely apposed
      to AORGs during radial migration in vivo and in vitro. Taken together, these data
      indicate a newly-identified population of radial glia-like cells in the adult OB
      that might function uniquely in neuronal radial migration during adult OB
      neurogenesis.

PMID- 22634212
TI  - Genetically encoded fluorescent voltage sensors using the voltage-sensing domain
      of Nematostella and Danio phosphatases exhibit fast kinetics.
AB  - A substantial increase in the speed of the optical response of genetically
      encoded fluorescent protein voltage sensors (FP voltage sensors) was achieved by
      using the voltage-sensing phosphatase genes of Nematostella vectensis and Danio
      rerio. A potential N. vectensis voltage-sensing phosphatase was identified in
      silico. The voltage-sensing domain (S1-S4) of the N. vectensis homolog was used
      to create an FP voltage sensor called Nema. By replacing the phosphatase with a
      cerulean/citrine FRET pair, a new FP voltage sensor was synthesized with fast off
      kinetics (Tau(off)<5ms). However, the signal was small (DeltaF/F=0.4%/200mV). FP
      voltage sensors using the D. rerio voltage-sensing phosphatase homolog,
      designated Zahra and Zahra 2, exhibited fast on and off kinetics within 2ms of
      the time constants observed with the organic voltage-sensitive dye, di4-ANEPPS.
      Mutagenesis of the S4 region of the Danio FP voltage sensor shifted the voltage
      dependence to more negative potentials but did not noticeably affect the kinetics
      of the optical signal.

PMID- 22634213
TI  - Hemispheric asymmetries in goal-directed hand movements are independent of hand
      preference.
AB  - Asymmetries in the kinematics and neural substrates of voluntary right and left
      eye-hand coordinated movements have been accredited to differential hemispheric
      specialization. An alternative explanation for between-hand movement differences
      could result from hand preference related effects. To test both assumptions, an
      experiment was conducted with left- and right-handers performing goal-directed
      movements with either hand paced by a metronome. Spatiotemporal accuracy was
      comparable between hands, whereas hand peak velocity was reached earlier when
      moving with the left compared to the right hand. The underlying brain activation
      patterns showed that both left- and right-handers activated more areas involved
      in visuomotor attention and saccadic control when using their left compared to
      the right hand. Altogether, these results confirm a unique perceptuomotor
      processing specialization of the left brain/right hand system that is independent
      of hand preference.

PMID- 22634214
TI  - Comparison of neural correlates of risk decision making between genders: an
      exploratory fNIRS study of the Balloon Analogue Risk Task (BART).
AB  - Functional magnetic resonance imaging (fMRI) research rarely reports gender
      differences in the neural correlates of risk decision making due to small sample
      sizes. In this functional near-infrared spectroscopy (fNIRS)-based imaging study
      of active and passive risk decision making, gender differences in oxygenated
      hemoglobin (HbO) concentration changes were investigated in the prefrontal cortex
      (PFC) of healthy adults. Forty adult participants (25-44 years; males=23)
      completed two sets of 15 balloon trials in active and passive decision making
      modes of the Balloon Analogue Risk Task (BART). In active mode, participants
      chose the number of balloon inflations, decided when to collect money, or risked
      accrued money if balloons exploded. BART is psychometrically well established and
      has predictive validity to real-world risk taking. The blocked experimental
      design and modification of BART for fNIRS were guided by a previous fMRI study
      that examined the neural correlates of risk decision making in young adults [Rao,
      H., Korczykowski, M., Pluta, J., Hoang, A., Detre, J.A., 2008. Neural correlates
      of voluntary and involuntary risk taking in the human brain: An fMRI study of the
      Balloon Analog Risk Task (BART). NeuroImage 42, 902-910]. Our findings were
      consistent with the previous fMRI study: no or little PFC activation during
      passive mode but strong PFC activation during active wins and losses among total
      sample. Active losses in females were associated with more significant bilateral
      activation in dorsal lateral prefrontal cortex (DLPFC) than males; no significant
      gender differences were found in DLPFC activation during active wins. Gender
      differences existed in direction and strength of correlations between BART
      behavioral and hemodynamic data. This study shows that use of fNIRS is a
      feasible, accessible, and less costly way to achieve adequate study power and
      investigate gender differences in neural correlates of risk decision making.

PMID- 22634215
TI  - Validating atlas-guided DOT: a comparison of diffuse optical tomography informed
      by atlas and subject-specific anatomies.
AB  - We describe the validation of an anatomical brain atlas approach to the analysis
      of diffuse optical tomography (DOT). Using MRI data from 32 subjects, we compare
      the diffuse optical images of simulated cortical activation reconstructed using a
      registered atlas with those obtained using a subject's true anatomy. The error in
      localization of the simulated cortical activations when using a registered atlas
      is due to a combination of imperfect registration, anatomical differences between
      atlas and subject anatomies and the localization error associated with diffuse
      optical image reconstruction. When using a subject-specific MRI, any localization
      error is due to diffuse optical image reconstruction only. In this study we
      determine that using a registered anatomical brain atlas results in an average
      localization error of approximately 18 mm in Euclidean space. The corresponding
      error when the subject's own MRI is employed is 9.1 mm. In general, the cost of
      using atlas-guided DOT in place of subject-specific MRI-guided DOT is a doubling
      of the localization error. Our results show that despite this increase in error,
      reasonable anatomical localization is achievable even in cases where the subject
      specific anatomy is unavailable.

PMID- 22634216
TI  - Attentional priorities and access to short-term memory: parietal interactions.
AB  - The intraparietal sulcus (IPS) has been implicated in selective attention as well
      as visual short-term memory (VSTM). To contrast mechanisms of target selection,
      distracter filtering, and access to VSTM, we combined behavioral testing,
      computational modeling and functional magnetic resonance imaging. Sixteen healthy
      subjects participated in a change detection task in which we manipulated both
      target and distracter set sizes. We directly compared the IPS response as a
      function of the number of targets and distracters in the display and in VSTM.
      When distracters were not present, the posterior and middle segments of IPS
      showed the predicted asymptotic activity increase with an increasing target set
      size. When distracters were added to a single target, activity also increased as
      predicted. However, the addition of distracters to multiple targets suppressed
      both middle and posterior IPS activities, thereby displaying a significant
      interaction between the two factors. The interaction between target and
      distracter set size in IPS could not be accounted for by a simple explanation in
      terms of number of items accessing VSTM. Instead, it led us to a model where
      items accessing VSTM receive differential weights depending on their behavioral
      relevance, and secondly, a suppressive effect originates during the selection
      phase when multiple targets and multiple distracters are simultaneously present.
      The reverse interaction between target and distracter set size was significant in
      the right temporoparietal junction (TPJ), where activity was highest for a single
      target compared to any other condition. Our study reconciles the role of middle
      IPS in attentional selection and biased competition with its role in VSTM access.

PMID- 22634217
TI  - Cerebral correlates of skin conductance responses in a cognitive task.
AB  - Changes in physiological arousal frequently accompany cognitive performance. Many
      studies sought to identify the neural correlates of heightened arousal as indexed
      by skin conductance responses (SCR). However, the observed regional activations
      may be confounded by task events. We addressed this issue by recording SCR in 25
      adults performing a stop signal task (SST) during functional magnetic resonance
      imaging. We compared only go trials with high and low SCR in order to isolate the
      event-independent processes. Furthermore, we distinguished go trials that
      followed another go, a stop success, or a stop error trial to examine whether the
      neural activities are contingent on the local context in which changes in SCR
      occurred. The results showed that the supplementary motor area responded to
      increased SCR irrespective of the preceding trial. The dorsal anterior cingulate
      cortex increased activation to heightened arousal most significantly in response
      to stop errors. The medial prefrontal cortex increased activation to SCR
      following a stop error but decreased activation following a go or stop success
      trial. These new findings specify the regional activations that accompany changes
      in physiological arousal during the SST and support distinct processes for the
      changes that occur under different local contexts. In particular, the MPFC shows
      opposing responses by increasing activation to changes in arousal evoked by
      salient stimuli and decreasing activation to the control of arousal.

PMID- 22634218
TI  - Functional activation of the infant cortex during object processing.
AB  - A great deal is known about the functional organization of the neural structures
      that mediate visual object processing in the adult observer. These findings have
      contributed significantly to our conceptual models of object recognition and
      identification and provided unique insight into the nature of object
      representations extracted from visual input. In contrast, little is known about
      the neural basis of object processing in the infant. The current research used
      near-infrared spectroscopy (NIRS) as a neuroimaging tool to investigate
      functional activation of the infant cortex during an object processing task that
      has been used extensively with infants. The neuroimaging data revealed that the
      infant cortex is functionally specialized for object processing (i.e.,
      individuation-by-feature) early in the first year but that patterns of activation
      also change between 3 and 12 months. These changes may reflect functional
      reorganization of the immature cortex or age-related differences in the cognitive
      processes engaged during the task.

PMID- 22634219
TI  - Involvement of the cerebellar cortex and nuclei in verbal and visuospatial
      working memory: a 7 T fMRI study.
AB  - The first aim of the present study was to extend previous findings of similar
      cerebellar cortical areas being involved in verbal and spatial n-back working
      memory to the level of the cerebellar nuclei. The second aim was to investigate
      whether different areas of the cerebellar cortex and nuclei contribute to
      different working memory tasks (n-back vs. Sternberg tasks). Young and healthy
      subjects participated in two functional magnetic resonance imaging (fMRI) studies
      using a 7 T MR scanner with its increased signal-to-noise ratio. One group of
      subjects (n=21) performed an abstract and a verbal version of an n-back task
      contrasting a 2-back and 0-back condition. Another group of subjects (n=23)
      performed an abstract and a verbal version of a Sternberg task contrasting a high
      load and a low load condition. A block design was used. For image processing of
      the dentate nuclei, a recently developed region of interest (ROI) driven
      normalization method of the dentate nuclei was applied (Diedrichsen et al.,
      2011). Whereas activated areas of the cerebellar cortex and dentate nuclei were
      not significantly different comparing the abstract and verbal versions of the n
      back task, activation in the abstract and verbal Sternberg tasks was
      significantly different. In both n-back tasks activation was most prominent at
      the border of lobules VI and Crus I, within lobule VII, and within the more
      caudal parts of the dentate nucleus bilaterally. In Sternberg tasks the most
      prominent activations were found in lobule VI extending into Crus I on the right.
      In the verbal Sternberg task activation was significantly larger within right
      lobule VI compared to the abstract Sternberg task and compared to the verbal n
      back task. Activations of rostral parts of the dentate were most prominent in the
      verbal Sternberg task, whereas activation of caudal parts predominated in the
      abstract Sternberg task. On the one hand, the lack of difference between abstract
      and verbal n-back tasks and the lack of significant lateralization suggest a more
      general contribution of the cerebellum to working memory regardless of the
      modality. On the other hand, the focus of activation in right lobule VI in the
      verbal Sternberg task suggests specific cerebellar contributions to verbal
      working memory. The verbal Sternberg task emphasizes maintenance of stimuli via
      phonological rehearsal, whereas central executive demands prevail in n-back
      tasks. Based on the model of working memory by Baddeley and Hitch (1974), the
      present results show that different regions of the cerebellum support functions
      of the central executive system and one of the subsidiary systems, the
      phonological loop.

PMID- 22634220
TI  - Determining functional connectivity using fMRI data with diffusion-based
      anatomical weighting.
AB  - There is strong interest in investigating both functional connectivity (FC) using
      functional magnetic resonance imaging (fMRI) and structural connectivity (SC)
      using diffusion tensor imaging (DTI). There is also emerging evidence of
      correspondence between functional and structural pathways within many networks
      (Greicius, et al., 2009; Skudlarski et al., 2008; van den Heuvel et al., 2009),
      although some regions without SC exhibit strong FC (Honey et al., 2008). These
      findings suggest that FC may be mediated by (direct or indirect) anatomical
      connections, offering an opportunity to supplement fMRI data with DTI data when
      determining FC. We develop a novel statistical method for determining FC, called
      anatomically weighted FC (awFC), which combines fMRI and DTI data. Our awFC
      approach implements a hierarchical clustering algorithm that establishes neural
      processing networks using a new distance measure consisting of two components, a
      primary functional component that captures correlations between fMRI signals from
      different regions and a secondary anatomical weight reflecting probabilities of
      SC. The awFC approach defaults to conventional unweighted clustering for specific
      parameter settings. We optimize awFC parameters using a strictly functional
      criterion, therefore our approach will generally perform at least as well as an
      unweighted analysis, with respect to intracluster coherence or autocorrelation.
      AwFC also yields more informative results since it provides structural properties
      associated with identified functional networks. We apply awFC to two fMRI data
      sets: resting-state data from 6 healthy subjects and data from 17 subjects
      performing an auditory task. In these examples, awFC leads to more highly
      autocorrelated networks than a conventional analysis. We also conduct a
      simulation study, which demonstrates accurate performance of awFC and confirms
      that awFC generally yields comparable, if not superior, accuracy relative to a
      standard approach.

PMID- 22634221
TI  - Total Flavonoids of Fructus Chorspondiatis inhibits collagen synthesis of
      cultured rat cardiac fibroblasts induced by angiotensin II: correlated with
      NO/cGMP signaling pathway.
AB  - AIM: To investigate the molecular mechanism of Total Flavonoids of Fructus
      Chorspondiatis (TFFC) on preventing cardiac fibroblasts collagen synthesis
      induced by angiotensin II. METHODS: Collagen synthesis was determined by
      measuring (3)H-proline incorporation cardiac fibroblasts and hydroxyproline
      content in the culture mediums. The expression of collagen types I and III mRNA
      and protein was measured by RT-PCR and western blot, respectively. NO level in
      the culture medium was measured by the Griess reagent. NOS level in the culture
      medium was measured by chemical colorimetric method. The cellular concentration
      of cyclic GMP (cGMP) was measured by radioimmunoassay. RESULTS: TFFC (25, 50, and
      100mg/L) inhibited collagen synthesis in cardiac fibroblasts in a dose-dependent
      manner compared with angiotensin II group (P<0.01), and the inhibitory effects
      were blocked by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) and
      1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ). TFFC increased nitric oxide
      (NO) and nitric oxide synthase (NOS) levels in the culture medium, increased
      intracellular cGMP level in cardiac fibroblasts, decreased collagen types I and
      III protein level in cardiac fibroblasts. The mRNA expression of collagen type I
      and III was suppressed by TFFC. CONCLUSIONS: These results suggested that TFFC
      inhibited collagen synthesis induced by angiotensin II in cardiac fibroblasts,
      and the inhibitory effect might associate with the activation of the NO/cGMP
      signaling pathway.

PMID- 22634222
TI  - Calcium channels blockers inhibit the signal transduction through the AtoSC
      system in Escherichia coli.
AB  - Verapamil, diltiazem and nifedipine are Ca(2+)-channel blockers used in
      cardiovascular diseases. We report here that the Escherichia coli AtoSC signaling
      is inhibited by those blockers. AtoSC two-component system plays a pivotal role
      in sophisticated signaling networks in E. coli regulating processes implicated in
      bacterial homeostasis and pathogenicity. The Ca(2+)-channel blockers abrogated
      the in vitro full-length AtoS kinase autophosphorylation. However, they
      demonstrated no effect on the AtoS cytoplasmic form autophosphorylation. AtoC
      protected AtoS from verapamil or diltiazem but not from nifedipine, when the two
      constituents formed complex. The blockers did not affect the AtoS~P to AtoC
      phosphotransfer. The blockers-mediated AtoSC inhibition was verified in vivo on
      the atoDAEB expression, which was inhibited only in AtoSC-expressing bacteria
      upon acetoacetate. The AtoS and AtoC protein or their genes transcription levels
      were unaffected by the blockers. Blockers demonstrated differential effects in
      the regulation of both the cytosolic- and most potently the membrane-bound-cPHB.
      Extracellular Ca(2+) counteracted the verapamil-mediated effect on cPHB only in
      atoSC(+) cells. Extracellular Ca(2+) reversed the diltiazem-mediated cPHB
      decreases in cells of both genetic backgrounds, yet a Ca(2+)-concentration
      dependent reversion was observed only in the AtoSC-regulated cPHB. Nifedipine
      caused a more pronounced cPHB down-regulation that was not reversed by
      extracellular Ca(2+). The AtoSC signaling inhibition by Ca(2+)-channel blockers
      used for human treatment, and their differential effects on cPHB-formed Ca(2+)
      channels, signify their implications in bacterial-host interactions through the
      two-component signaling and could stimulate the design of Ca(2+)-channels
      blockers derivatives acting as inhibitors of two-component systems.

PMID- 22634223
TI  - DFT calculation of vibrational frequencies of clusters in GaAs and the Raman
      spectra.
AB  - We have calculated the vibrational frequencies of clusters of Ga and As atoms
      from the first principles using the density-functional theory (DFT) method and
      the local-density approximation (LDA). We find that the calculated value of 286.2
      cm(-1) for a linear cluster of Ga(2)As(2) is very near the experimental value of
      292 +/- 4 cm(-1). The calculated value of 289.4 cm(-1) for Ga(2)As(6) (dumb bell)
      cluster is indeed very near the experimental value. There are strong phonon
      correlations so that the cluster frequency is within the dispersion relation of
      the crystal LO value. There is a weak line in the experimental Raman spectrum at
      268 cm(-1) which is very near the value of 267.3 cm(-1) calculated for the
      Ga(2)As (triangular) cluster. The weak lines corresponding to the linear bonds
      provide the strength to the amorphous samples. There are clusters of atoms in the
      glassy state of GaAs.

PMID- 22634224
TI  - The role of amino acid transporters in GSH synthesis in the blood-brain barrier
      and central nervous system.
AB  - Glutathione (GSH) plays a critical role in protecting cells from oxidative stress
      and xenobiotics, as well as maintaining the thiol redox state, most notably in
      the central nervous system (CNS). GSH concentration and synthesis are highly
      regulated within the CNS and are limited by availability of the sulfhydryl amino
      acid (AA) l-cys, which is mainly transported from the blood, through the blood
      brain barrier (BBB), and into neurons. Several antiporter transport systems
      (e.g., x(c)(-), x(-)(AG), and L) with clearly different luminal and abluminal
      distribution, Na(+), and pH dependency have been described in brain endothelial
      cells (BEC) of the BBB, as well as in neurons, astrocytes, microglia and
      oligodendrocytes from different brain structures. The purpose of this review is
      to summarize information regarding the different AA transport systems for l-cys
      and its oxidized form l-cys(2) in the CNS, such as expression and activity in
      blood-brain barrier endothelial cells, astrocytes and neurons and environmental
      factors that modulate transport kinetics.

PMID- 22634226
TI  - Intermittent PTH (1-34) injection rescues the retarded skeletal development and
      postnatal lethality of mice mimicking human achondroplasia and thanatophoric
      dysplasia.
AB  - Achondroplasia (ACH) and thanatophoric dysplasia (TD) are caused by gain-of
      function mutations of fibroblast growth factor receptor 3 (FGFR3) and they are
      the most common forms of dwarfism and lethal dwarfism, respectively. Currently,
      there are few effective treatments for ACH. For the neonatal lethality of TD
      patients, no practical effective therapies are available. We here showed that
      systemic intermittent PTH (1-34) injection can rescue the lethal phenotype of TD
      type II (TDII) mice and significantly alleviate the retarded skeleton development
      of ACH mice. PTH-treated ACH mice had longer naso-anal length than ACH control
      mice, and the bone lengths of humeri and tibiae were rescued to be comparable
      with those of wild-type control mice. Our study also found that the premature
      fusion of cranial synchondroses in ACH mice was partially corrected after the PTH
      (1-34) treatment, suggesting that the PTH treatment may rescue the progressive
      narrowing of neurocentral synchondroses that cannot be readily corrected by
      surgery. In addition, we found that the PTH treatment can improve the osteopenia
      and bone structure of ACH mice. The increased expression of PTHrP and down
      regulated FGFR3 level may be responsible for the positive effects of PTH on bone
      phenotype of ACH and TDII mice.

PMID- 22634225
TI  - Human fetal skeletal muscle contains a myogenic side population that expresses
      the melanoma cell-adhesion molecule.
AB  - Muscle side population (SP) cells are rare myogenic progenitors distinct from
      satellite cells, the known tissue-specific stem cells of skeletal muscle. Studies
      in mice demonstrated that muscle SP cells give rise to satellite cells in vivo.
      Given that muscle SP cells are heterogeneous, it has been difficult to
      prospectively enrich for myogenic progenitors within the SP fraction,
      particularly from human tissue. Further, conditions that favor the expansion of
      human muscle SP cells while retaining their myogenic potential have yet to be
      reported. In this study, human fetal muscle SP and main population (MP) cells
      were purified based on the expression of melanoma cell adhesion molecule (MCAM),
      a marker we previously reported to enrich for cells with myogenic potential. To
      define the relationship between MCAM expression and the degree of myogenic
      commitment, single cells were analyzed for the expression of myogenic-specific
      markers. Myogenic factors strongly associated with MCAM expression in single
      cells, particularly Myf5. Different MCAM+ populations, including SP cells, were
      expanded and assayed for fusion potential in vitro and engraftment potential in
      vivo. All MCAM+ subpopulations fused robustly into myotubes in vitro, whereas the
      MCAM- subpopulations did not. Further, MCAM+ SP cells exhibited the highest
      fusion potential in vitro and were the only fraction to engraft in vivo, although
      at low levels, following propagation. Thus, MCAM can be used to prospectively
      enrich for myogenic muscle SP cells in human fetal muscle. Moreover, we provide
      evidence that human MCAM+ SP cells have intrinsic myogenic activity that is
      retained after propagation.

PMID- 22634228
TI  - Layered activation of epicardial scar in arrhythmogenic right ventricular
      dysplasia: possible substrate for confined epicardial circuits.
AB  - BACKGROUND: Ventricular tachycardia ablation in arrhythmogenic right ventricular
      dysplasia (ARVD) is more successful when including epicardial ablation. Scarring
      may cause independent, layered epicardial activation and promote epicardially
      confined ventricular tachycardia circuits. We aimed to characterize transmural
      right ventricular activation in ARVD patients and to compare this with reference
      patients without structural heart disease. METHODS AND RESULTS: Eighteen ARVD
      patients underwent detailed endocardial and epicardial sinus rhythm
      electroanatomic mapping. Bipolar activation was annotated at the sharpest
      intrinsic deflection including late potentials and compared with 6 patients with
      normal hearts. Total scar area was larger on the epicardium (97+/-78 cm(2)) than
      the endocardium (57+/-44 cm(2); P=0.04), with significantly more isolated
      potentials. Total epicardial activation time was longer than endocardial (172+/
      54 versus 99+/-27 ms; P<0.01), and both were longer than in reference patients.
      Earliest endocardial site was the right ventricular anteroseptum in 17 of 18 ARVD
      patients versus 5 of 6 controls (P=0.446), and latest endocardial site was in the
      outflow tract in 13 of 18 ARVD patients versus 4 of 6 controls and tricuspid
      annulus in 5 of 18 ARVD patients versus 2 of 6 controls (P=1.00). In reference
      patients, epicardial activation directly opposite endocardial sites occurred in
      5.2+/-1.9 ms, suggesting direct transmural activation. In contrast, ARVD patients
      had major activation delay to the epicardium with laminar central scar activation
      from the scar border, not by direct transmural spread from the endocardium.
      CONCLUSIONS: Transmural right ventricular activation is modified by ARVD scarring
      with a delayed epicardial activation sequence suggestive of independent rather
      than direct transmural activation. This may predispose ventricular tachycardia
      circuits contained entirely within the epicardium in ARVD and explains
      observations on the need for direct epicardial ablation to eliminate ventricular
      tachycardia.

PMID- 22634227
TI  - Alternate glucocorticoid receptor ligand binding structures influence outcomes in
      an in vivo tissue regeneration model.
AB  - Since their characterization, glucocorticoids (GCs), the most commonly prescribed
      immunomodulatory drugs, have undergone numerous structural modifications designed
      to enhance their activity. In vivo assessment of these corticosteroid analogs is
      essential to understand the difference in molecular signaling of the ligands that
      share the corticosteroid backbone. Our research identified a novel function of
      GCs as modulators of tissue regeneration and demonstrated that GCs activate the
      glucocorticoid receptor (GR) to inhibit early stages of tissue regeneration in
      zebrafish (Danio rerio). We utilized this phenomenon to assess the effect of
      different GC analogs on tissue regeneration and identified that some GCs such as
      beclomethasone dipropionate (BDP) possess inhibitory properties, while others,
      such as dexamethasone and hydrocortisone have no effect on regeneration. We
      performed in silico molecular docking and dynamic studies and demonstrated that
      type and size of substitution at the C17 position of the cortisol backbone confer
      a unique stable conformation to GR on ligand binding that is critical for
      inhibitory activity. In the field of tissue regeneration, our study is one of the
      first Structure Activity Relationship (SAR) investigations performed in
      vertebrates demonstrating that the in vivo tissue regeneration model is a
      powerful tool to probe structure function relationships, to understand
      regenerative biology, and to assist in rational drug design.

PMID- 22634229
TI  - WIN55212-2 attenuates amyloid-beta-induced neuroinflammation in rats through
      activation of cannabinoid receptors and PPAR-gamma pathway.
AB  - Cannabinoids have been shown to exert neuroprotective effects in a plethora of
      neurodegenerative conditions. Over the past decade, some studies demonstrate that
      cannabinoids can interact with nuclear peroxisome proliferator-activated
      receptors (PPARs). We investigated protective properties of WIN55212-2 (WIN, a
      non-selective cannabinoid receptor agonist) in beta-amyloid (Abeta)-induced
      neurodegeneration in rat hippocampus and possible involvement of PPAR-gamma (PPAR
      gamma). Abeta (1-42) was injected into the hippocampus of male rats. Animals were
      administered by intracerebroventricular rout the following treatments on days 1,
      3, 5, 7: vehicle, WIN, GW9662 (selective PPAR-gamma antagonist) plus WIN, AM251
      (selective CB1 receptor antagonist) plus WIN, SR144528 (selective CB2 receptor
      antagonist) plus WIN, each of antagonists alone. Injection of Abeta-induced
      spatial memory impairment and a dramatic rise in hippocampal TNF-alpha, active
      caspase 3, nuclear NF-kB levels and TUNEL-positive neurons. WIN administration
      significantly improved memory function and diminished the elevated levels of
      these markers, while antagonizing either CB1 or CB2 receptor subtype partially
      attenuated the protective effects. Intriguingly, WIN significantly increased PPAR
      gamma level and transcriptional activity, the latter being partially inhibited
      with AM251 but not with SR144528. The enhancing effect on PPAR-gamma pathway was
      crucial to WIN-induced neuroprotection since GW9662 partially reversed the
      beneficial actions of WIN. Co-administration of the three antagonists led to the
      complete abrogation of WIN effects. Our findings indicate that WIN exerts
      neuroprotective and anti-inflammatory actions against Abeta damage through both
      CB1 and CB2 receptors. Of great note, both direct and CB1-mediated increase in
      PPAR-gamma signaling also contributes to WIN-induced neuroprotection.

PMID- 22634230
TI  - Relationship between arm usage and instrumental activities of daily living after
      unilateral stroke.
AB  - OBJECTIVE: To determine whether the preferred pattern of arm use after unilateral
      hemispheric damage was associated with better everyday functioning. Our previous
      work showed that right-handed stroke patients with right hemisphere damage (RHD)
      used their right, ipsilesional arm most frequently, while those with left
      hemisphere damage (LHD) used both arms together most frequently. This effect was
      explained by right-hand preference, but its relationship to functional
      performance is not known. DESIGN: Observational cohort. SETTING: Research
      laboratory. PARTICIPANTS: Stroke patients (n=60; 30 RHD, 30 LHD) and healthy
      controls (n=52). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The
      Functional Impact Assessment was used to assess performance on instrumental
      activities of daily living (IADLs). RESULTS: The preferred patterns of arm use
      were similar to those in our previous report. However, it was the greater use of
      both arms together that was associated with better IADL performance in both
      stroke groups. Ipsilesional arm use alone was not significantly associated with
      IADL performance in the RHD group and was associated with poorer performance in
      the LHD group. CONCLUSIONS: The modal arm use pattern did not always optimize
      IADL functioning. Better IADL functioning in both stroke groups was associated
      with the use of both arms together, which is the most common arm use pattern of
      healthy individuals doing these same IADLs. An important practical question that
      arises from these findings is whether bilateral arm rehabilitation should be
      emphasized, because using both arms together is the best predictor of better
      performance on everyday tasks.

PMID- 22634231
TI  - Validity and reliability of the perceived deficit questionnaire to assess
      cognitive symptoms in people with chronic whiplash-associated disorders.
AB  - OBJECTIVE: To investigate the validity and reliability of the Perceived Deficit
      Questionnaire (PDQ) for use in people with chronic whiplash-associated disorders.
      DESIGN: Cross-sectional. SETTING: Tertiary institution. PARTICIPANTS: Patients
      (N=105) with chronic whiplash-associated disorders and asymptomatic controls
      (n=50). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The 20-item PDQ
      inclusive of 4 sections (attention/concentration, retrospective memory,
      prospective memory, and organization/planning) rated on a 5-point scale. RESULTS:
      Internal construct validity of the PDQ was examined by Rasch analysis, confirming
      the appropriateness of its 5-point scale and the unidimensionality of each
      section after modification by eliminating 1 item each from the
      attention/concentration and retrospective memory sections. Preliminary evidence
      was also gained for external construct validity (convergent validity) of the
      modified PDQ by demonstrating significant (P<.05) correlations of all sections
      with a global measure of disability due to neck pain (the Neck Disability Index).
      The whiplash group demonstrated significantly (P<.05) higher scores in each
      section of the modified PDQ than did the control group, indicating evidence for
      discriminant validity. In addition, the modified PDQ demonstrated good internal
      consistency (Rasch-generated reliability >.8) and acceptable test-retest
      reliability with 1-month interval (intraclass correlation coefficients >.8).
      CONCLUSIONS: The modified PDQ appears to be a valid and reliable questionnaire
      and could be used quickly in clinical practice to gain a basic understanding of
      perceived cognitive symptoms in people with chronic whiplash-associated
      disorders.

PMID- 22634232
TI  - Stimulation of shank muscles during functional electrical stimulation cycling
      increases ankle excursion in individuals with spinal cord injury.
AB  - OBJECTIVE: To investigate the effect of shank muscle stimulation on ankle joint
      excursion during passive and functional electrical stimulation (FES) leg cycling.
      DESIGN: Within-subject comparisons. SETTING: Laboratory setting. PARTICIPANTS:
      Well-trained FES cyclists (N=7) with chronic spinal cord injuries. INTERVENTIONS:
      Two experimental sessions were performed on an isokinetic FES cycle ergometer
      with a pedal boot that allowed the ankle to plantarflex and dorsiflex during
      cycling. During the first session, the optimal stimulation timings to induce
      plantarflexion and dorsiflexion were investigated by systematically altering the
      stimulation angles of the shank muscles (tibialis anterior [TA] and triceps surae
      [TS]). During the second session, TA and TS stimulation was included with
      standard FES cycling (quadriceps, hamstrings, and gluteals) for 6 subjects. MAIN
      OUTCOME MEASURES: Ankle, knee, and hip movements were analyzed using 2
      dimensional video. RESULTS: The ankle excursions during passive cycling were 19
      degrees +/-6 degrees . TA and TS stimulation increased ankle joint excursion up
      to 33 degrees +/-10 degrees  and 27 degrees +/-7 degrees , respectively. Compared
      with passive cycling, ankle joint excursion was not significantly increased
      during standard FES cycling (24 degrees +/-7 degrees ). TA and TS stimulation
      significantly increased the ankle excursion when applied during standard FES
      cycling (41 degrees +/-4 degrees ). CONCLUSIONS: Freeing the ankle joint to
      rotate during FES cycling was found to be safe. The combination of shank muscle
      stimulation and repetitive ankle joint movement may be beneficial for improving
      ankle flexibility and leg conditioning. Further research is required to test and
      design ankle supports that might maximize the benefits of shank muscle
      activation.

PMID- 22634234
TI  - GE-25-like immunoreactivity in the rat eye.
AB  - This study aimed to investigate the presence and distribution of the chromogranin
      A-derived peptide GE-25 in the rat eye. The molecular form detected by the GE-25
      antiserum was evaluated in the rat trigeminal ganglion, retina and remaining
      tissues of the rat eye by means of Western blots and the distribution pattern of
      GE-25-like immunoreactivity was studied in the rat eye and rat trigeminal
      ganglion by immunofluorescence. One single band of approximately 70kDa was
      stained in the trigeminal ganglion and retina which represents the uncleaved
      intact chromogranin A indicating that the proteolytic processing of chromogranin
      A to GE-25 is limited in these tissues. Sparse GE-25-like immunoreactive nerve
      fibers were visualized in the corneal stroma, at the limbus around blood vessels,
      in the sphincter and dilator muscle and stroma of the iris, in the stroma of the
      ciliary body and ciliary processes and in the stroma and around blood vessels in
      the choroid. This distribution pattern is characteristic for neuropeptides
      whereas the presence of immunoreactivity in the corneal endothelium and in Muller
      glia in the retina is atypical. GE-25-like immunoreactivity was found in small to
      medium-sized ganglion cells in the rat trigeminal ganglion clearly indicating
      that the nerve fibers in the rat eye are of sensory origin. The colocalization of
      GE-25-immunoreactivity with SP-immunoreactivity in the rat ciliary body is in
      agreement with the presumption of the sensory nature of the innervation of the
      anterior segment of the eye by GE-25.

PMID- 22634233
TI  - The antimicrobial activity of the appetite peptide hormone ghrelin.
AB  - The present study examined the antimicrobial activity of the peptide ghrelin.
      Both major forms of ghrelin, acylated ghrelin (AG) and desacylated ghrelin (DAG),
      demonstrated the same degree of bactericidal activity against Gram-negative
      Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa), while
      bactericidal effects against Gram-positive Staphylococcus aureus (S. aureus) and
      Enterococcus faecalis (E. faecalis) were minimal or absent, respectively. To
      elucidate the bactericidal mechanism of AG and DAG against bacteria, we monitored
      the effect of the cationic peptides on the zeta potential of E. coli. Our results
      show that AG and DAG similarly quenched the negative surface charge of E. coli,
      suggesting that ghrelin-mediated bactericidal effects are influenced by charge
      dependent binding and not by acyl modification. Like most cationic antimicrobial
      peptides (CAMPs), we also found that the antibacterial activity of AG was
      attenuated in physiological NaCl concentration (150mM). Nonetheless, these
      findings indicate that both AG and DAG can act as CAMPs against Gram-negative
      bacteria.

PMID- 22634235
TI  - Occurrence of cardiovascular calcifications in normal, aging rats.
AB  - BACKGROUND: Cardiovascular calcification is an independent predictor of morbidity
      and mortality and increases with age. Animal models are frequently used to
      investigate the underlying pathophysiology. Only scarce data regarding the effect
      of aging on calcifications in these animal models are available. The aim of this
      study is to investigate the occurrence of cardiovascular calcifications in
      normal, aging rats. METHODS: A mixed inbred/outbred population of 44 male
      Lewis/Wistar rats was studied. Group 1 of three-month-old rats, group 2 twelve
      month-old, group 3 twenty-four-month-old and group 4 thirty-month-old rats.
      Calibrated integrated backscatter (cIB) values and blood parameters (creatinine,
      parathyroid hormone (PTH)) were measured, followed by ex-vivo micro-CT and
      histology as reference methods. RESULTS: Cardiovascular calcifications developed
      with age, as demonstrated by significantly increasing cIB values of the aortic
      valve and myocardium. This was confirmed by a significant increase in the
      calcified volume on ex-vivo micro-CT and in the histological calcium score. There
      was also a significantly higher level of creatinine and PTH with age.
      CONCLUSIONS: As in humans, cardiovascular calcifications progressively increase
      with age in the normal rat. Therefore the aging rat model could be used for
      studying calcifying cardiovascular disease. cIB might have a value in future
      studies for the early detection of subclinical calcifications in humans.

PMID- 22634236
TI  - Full factorial design, physicochemical characterisation and biological assessment
      of cyclosporine A loaded cationic nanoparticles.
AB  - Cyclosporine A loaded poly(lactide-co-glycolide) nanoparticles coated with
      chitosan were prepared using the o/w emulsification solvent evaporation method. A
      2(3) full factorial design was used to investigate the effect of 3 preparation
      parameters on the particle size, polydispersity index, zeta potential and drug
      release. In vitro experiments were performed in order to evaluate the
      cytotoxicity and anti-inflammatory activity of the developed nanoparticles.
      Particle sizes varied from 156 nm to 314 nm, and polydispersity index values of
      0.07-0.56 were obtained depending on the different preparation parameters. All
      nanoparticles showed positive zeta potential values. Nanoparticles prepared with
      the highest concentration chitosan retained a positive zeta potential after
      dispersion in simulated lachrymal fluid, which supports the possibility of an
      electrostatic interaction between these particles and the negatively charged
      mucus layer at the eye. The in vitro release profile of cyclosporine A from the
      chitosan-coated nanoparticles was strongly dependent on the release medium used.
      None of the cationic nanoparticle formulations showed significant cytotoxicity
      compared to the negative control using human epithelial cells (HaCaT).
      Cyclosporine A encapsulated in the various nanoparticle formulations remained
      anti-inflammatory active as significant suppression of interleukine-2 secretion
      in concanavalin A stimulated Jurkat T cells was observed.

PMID- 22634237
TI  - Development of a novel probe sonication assisted enhanced loading of 5-FU in
      SPION encapsulated pectin nanocarriers for magnetic targeted drug delivery
      system.
AB  - A novel probe sonication method is developed to enhance loading of 5-fluorouracil
      (5-FU) in SPION encalsulated pectin nanocarriers of 100-150 nm size (referred
      here as MP-5FU nanocarriers). Probe sonication at 20 kHz for 60 min resulted in 5
      FU loading efficiency of 33.2 +/- 2.5%w/w and corresponding drug loading content
      of 18.2 +/- 1.1 wt%. These are two folds higher than literature report of 5-FU
      loading in pectin. The enhanced loading is attributed to increase in the rate of
      dissolution of 5-FU in pectin due to transmission of kHz order sonic waves which
      increases temperature and pressure in the medium due to formation and collapsing
      of cavitation bubbles. The fabricated MP-5FU nanocarriers with saturation
      magnetization (43.13 emu/g) exhibited pH responsive, swelling controlled in vitro
      release of 5-FU in simulated gastric fluid at pH 1.2, in simulated intestinal
      fluid at pH 6.8, in simulated colonic fluid at pH 5.5, and in phosphate buffer
      solution at pH 7.4. The cytotoxicity of MP-5FU was measured by sulforhodamine B
      (SRB) assay and its GI(50) was more than 5mg/mL for cancer cells of HT-29 (colon)
      and Hep G2 (liver), while it was 3.7 mg/mL for cancer cells of MIA-PaCa-2
      (Pancreas).

PMID- 22634238
TI  - Characterization of fluorescent poly(isobutylcyanoacrylate) nanoparticles
      obtained by copolymerization of a fluorescent probe during Redox Radical Emulsion
      Polymerization (RREP).
AB  - PURPOSE: The purpose of the work was to demonstrate that a polymerizable
      fluorescent labeled was incorporated in the core of chitosan/pluronic(r) F68
      coated Poly(IsobutylCyanoAcrylate) (PIBCA) nanoparticles thanks to a covalent
      linkage. It was also aimed to show that the labeling did not modify the
      complement activation capacity of the nanoparticles which are designed as drug
      carriers for the in vivo delivery of siRNA. METHOD: Fluorescent nanoparticles
      were prepared by adding a fluorescent monomer dye, methacryloxyethyl
      thiocarbamoyl rhodamine B during the preparation of nanoparticles by redox
      radical emulsion polymerization. The structure and composition of the fluorescent
      nanoparticles was investigated. The capacity of the fluorescent nanoparticles to
      activate the complement system was evaluated by 2D immunoelectrophoresis.
      RESULTS: Results from the analysis of the composition and structure of polymers
      forming the nanoparticles showed that the fluorescent dye was incorporated in the
      core of the nanoparticles by formation of a stable covalent linkage with PIBCA.
      The labeled nanoparticles showed the same surface properties as the corresponding
      non-labeled nanoparticles based on analysis of the polymer structure,
      physicochemical properties and evaluation of their capacity to activate the
      complement system. CONCLUSION: This work showed that the fluorescent PIBCA
      nanoparticles were labeled by incorporation of the fluorescent probe in the
      nanoparticle core and that the fluorescent probe did not modify the nanoparticle
      surface properties. These fluorescent nanoparticles can be proposed as relevant
      models to investigate how they deliver siRNA to their biological target in cell
      cultures and during in vivo experiments.

PMID- 22634239
TI  - Rhomboid proteases in mitochondria and plastids: keeping organelles in shape.
AB  - Rhomboids constitute the most widespread and conserved family of intramembrane
      cleaving proteases. They are key regulators of critical cellular processes in
      bacteria and animals, and are poised to play an equally important role also in
      plants. Among eukaryotes, a distinct subfamily of rhomboids, prototyped by the
      mammalian mitochondrial protein Parl, ensures the maintenance of the structural
      and functional integrity of mitochondria and plastids. Here, we discuss the
      studies that in the past decade have unveiled the role, regulation, and structure
      of this unique group of rhomboid proteases. This article is part of a Special
      Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids.

PMID- 22634240
TI  - Convergent evolution of morphological and ecological traits in the open-habitat
      chat complex (Aves, Muscicapidae: Saxicolinae).
AB  - Open-habitat chats (genera Myrmecocichla, Cercomela, Oenanthe and relative) are a
      morphologically and ecologically cohesive group of genera with unclear
      phylogenetic relationships. They are distributed mostly in open, arid and/or
      rocky habitats of Africa and Eurasia. Here, we present the most comprehensive
      molecular phylogenetic analysis of this group to date, with a complete taxon
      sampling at the species level. The analysis, based on a multilocus dataset
      including three mitochondrial and three nuclear loci, allows us to elucidate the
      phylogenetic relationships and test the traditional generic limits. All genera
      are non-monophyletic, suggesting extensive convergence on similar plumage
      patterns in unrelated species. While the colour pattern appear to be a poor
      predictor of the phylogenetic relationships, some of the ecological and
      behavioural traits agree relatively well with the major clades. Following our
      results, we also propose a revised generic classification for the whole group.

PMID- 22634241
TI  - Phylogeny of North African Agama lizards (Reptilia: Agamidae) and the role of the
      Sahara desert in vertebrate speciation.
AB  - The origin of Saharan biodiversity is poorly understood, in part because the
      geological and paleoclimatic events that presumably shaped species diversity are
      still controversial, but also because few studies have explored causal
      explanations for the origin of Saharan diversity using a phylogenetic framework.
      Here, we use mtDNA (16S and ND4 genes) and nDNA (MC1R and CMOS genes) to infer
      the relationships and biogeographic history of North African agamas (genus
      Agama). Agamas are conspicuous, diverse and abundant African lizards that also
      occur in the Saharan xeric and mesic environments. Our results revealed the
      presence of three Agama lineages in North Africa: one Afrotropical, one Sahelo
      Saharan, and one broadly distributed in North Africa and mainly Saharan. Southern
      Mauritania contains the highest known diversity, with all three lineages present.
      Results suggest that agamas colonized the Sahara twice, but only one lineage was
      able to radiate and diversify there. Species in the Saharan lineage are mostly
      allopatric, and their splitting, genetic diversity and distribution are greatly
      explained by mountain ranges. One species in this lineage has colonized the
      Mediterranean climatic zone (A. impalearis), and another one the Sahel savannah
      (A. boueti). The other lineage to colonize the Sahara corresponds to A.
      boulengeri, an eminently Sahelian species that also inhabits Saharan mountain
      ranges in Mauritania and Mali. Phylogenetic analyses indicate that allopatric
      montane populations within some currently recognized species are also genetically
      divergent. Our study therefore concludes that vicariant speciation is a leading
      motor of species diversification in the area: Inside the Sahara, associated to
      mountain-ranges isolated by dune seas and bare plains; outside, associated to
      less harsh climates to the North and South. Paleoclimatic oscillations are
      suggested as causal explanations of the vicariant distribution and origin of
      species. Agamas are thought to have colonized northern Africa during wet periods,
      with subsequent dry periods fragmenting species distribution and leading to
      allopatric populations associated to milder and wetter climates in the
      Mediterranean, Sahel, and in Saharan mountains, in an island-model fashion.
      Finally, our results support the synonymization of A. castroviejoi with A.
      boueti, the reciprocal monophyly of all other North African agamas, and suggest
      one candidate species within A. boulengeri.

PMID- 22634242
TI  - Ten questions: developmentally appropriate support for pediatric testing in young
      children--how you can help.

PMID- 22634243
TI  - Desmopressin in the postural tachycardia syndrome.

PMID- 22634244
TI  - Simulation and clinical training: the future and the indispensable past.

PMID- 22634245
TI  - Challenges and opportunities for the implementation of the Three Rs in Canadian
      vaccine quality control.
AB  - A case-study approach was used to identify opportunities and challenges to the
      implementation of the Three Rs in vaccine testing in Canada. Data was obtained
      through interviews with 16 Canadian stakeholders involved in the production,
      testing and evaluation of vaccines. Participants identified inconsistent
      regulatory testing requirements, the lack of biological functionality of some in
      vitro methods, the benchmarking of in vitro against in vivo assays, and high
      caution towards method changes as major challenges to implementation.
      Opportunities to implementation were identified as the desire for and steps taken
      towards harmonization of test methods between countries, collaborations on new
      method development, the poor performance of traditional animal methods, the
      domino effect of one regulatory authority accepting a method after another, and
      stakeholder concerns for the ethical care and use of animals used in vaccine
      testing. These results suggest that industry and the Canadian government are open
      to implementing the Three Rs in vaccine quality control, but methods adopted must
      be reliable and biologically relevant. Improving the harmonization of regulatory
      requirements will assist in furthering the implementation of alternative methods.

PMID- 22634246
TI  - Lack of effect of menthol level and type on smokers' estimated mouth level
      exposures to tar and nicotine and perceived sensory characteristics of cigarette
      smoke.
AB  - Menthol can reduce sensory irritation and it has been hypothesised that this
      could result in smokers of mentholated cigarettes taking larger puffs and deeper
      post-puff inhalations thereby obtaining higher exposures to smoke constituents
      than smokers of non-mentholated cigarettes. The aim of our study was to use part
      filter analysis methodology to assess the effects of cigarette menthol loading on
      regular and occasional smokers of mentholated cigarettes. We measured mouth level
      exposure to tar and nicotine and investigated the effects of mentholation on
      smokers' sensory perceptions such as cooling and irritation. Test cigarettes were
      produced containing no menthol and different loadings of synthetic and natural l
      menthol at 1 and 4mg ISO tar yields. A target of 100 smokers of menthol
      cigarettes and 100 smokers who predominantly smoked non-menthol cigarettes from
      both 1 and 4mg ISO tar yield categories were recruited in Poland and Japan. Each
      subject was required to smoke the test cigarette types of their usual ISO tar
      yield. There were positive relationships between menthol loading and the
      perceived 'strength of menthol taste' and 'cooling' effect. However, we did not
      see marked menthol-induced reductions in perceived irritation or menthol-induced
      increases in mouth level exposure to tar and nicotine.

PMID- 22634248
TI  - Contrasting brain activity patterns for item recognition memory and associative
      recognition memory: insights from immediate-early gene functional imaging.
AB  - Recognition memory, the discrimination of a novel from a familiar event, can be
      classified into item recognition and associative recognition. Item recognition
      concerns the identification of novel individual stimuli, while associative
      recognition concerns the detection of novelty that arises when familiar items are
      reconfigured in a novel manner. Experiments in rodents that have mapped the
      expression of immediate-early genes, e.g., c-fos, highlight key differences
      between these two forms of recognition memory. Visual item novelty is
      consistently linked to increased c-fos activity in just two brain sites, the
      perirhinal cortex and the adjacent visual association area Te2. Typically there
      are no hippocampal c-fos changes. In contrast, visual associative recognition is
      consistently linked to c-fos activity changes in the hippocampus, but not the
      perirhinal cortex. The lack of a c-fos perirhinal change with associative
      recognition presumably reflects the fact that the individual items in an array
      remain familiar, even though their combinations are unique. Those exceptions,
      when item recognition is associated with hippocampal c-fos changes, occur when
      rats actively explore novel objects. The increased engagement with objects will
      involve multisensory stimulus processing and potentially create conditions in
      which rats can readily learn stimulus attributes such as object location or
      object order, i.e., attributes involved in associative recognition. Correlations
      based on levels of immediate-early gene expression in the temporal lobe indicate
      that actively exploring novel stimuli switches patterns of entorhinal-hippocampal
      functional connectivity to emphasise direct entorhinal-dentate gyrus processing.
      These gene activity findings help to distinguish models of medial temporal lobe
      function.

PMID- 22634247
TI  - Dorsolateral prefrontal contributions to human intelligence.
AB  - Although cognitive neuroscience has made remarkable progress in understanding the
      involvement of the prefrontal cortex in executive control functions for human
      intelligence, the necessity of the dorsolateral prefrontal cortex (dlPFC) for key
      competencies of general intelligence and executive function remains to be well
      established. Here we studied human brain lesion patients with dlPFC lesions to
      investigate whether this region is computationally necessary for performance on
      neuropsychological tests of general intelligence and executive function,
      administering the Wechsler Adult Intelligence Scale (WAIS) and subtests of the
      Delis Kaplan Executive Function System (D-KEFS) to three groups: dlPFC lesions
      (n=19), non-dlPFC lesions (n=152), and no brain lesions (n=55). The results
      indicate that: (1) patients with focal dlPFC damage exhibit lower scores, at the
      latent variable level, than controls in general intelligence (g) and executive
      function; (2) dlPFC patients demonstrate lower scores than controls in several
      executive measures; and (3) these latter differences are no longer significant
      when the pervasive influence of the general factor of intelligence (g) is
      statistically removed. The observed findings support a central role for the dlPFC
      in global aspects of general intelligence and make specific recommendations for
      the interpretation and application of the WAIS and D-KEFS to the study of high
      level cognition in health and disease.

PMID- 22634249
TI  - Decreased oxidative stress during glycolytic inhibition enables maintenance of
      ATP production and astrocytic survival.
AB  - Depressed energy metabolism and oxidative stress are common features in many
      pathological situations in the brain, including stroke. In order to investigate
      astrocytic responses to such stress, we induced metabolic depression in cultured
      rat astrocytes. Iodoacetate (IA), an inhibitor of the glycolytic enzyme
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used and resulted in a rapid
      inhibition of GAPDH activity. After 1h of GAPDH inhibition the ATP levels started
      to decrease and were completely abolished at 4h. In parallel, the activity of
      reactive oxygen species (ROS) was significantly increased, followed by extensive
      cell death involving flipping of phosphatidylserine and translocation of
      apoptosis-inducing factor, but not caspase-3 activation. When IA was combined
      with azide, a respiratory chain complex IV inhibitor, the ATP levels decreased
      immediately. Interestingly, with azide present, the ROS activity remained low and
      the astrocytes remained viable even at very low ATP levels. Addition of exogenous
      ROS-scavengers prevented the IA-induced ROS activity, the ATP levels were
      maintained and cell death was prevented. Similar protection could be obtained
      when astrocytes, prior to addition of IA, were incubated with substances known to
      activate the nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated
      endogenous antioxidant system. When IA was washed out, after a relatively
      moderate ATP depression, massive cell death occurred. This was efficiently
      prevented by addition of azide or ROS scavengers during the IA treatment or by
      pre-activation of the Nrf2 system. Our results demonstrate that astrocytes in
      culture can endure and recover from glycolytic inhibition if the ROS activity
      remained at a low level and suggest that oxidative stress can be an important
      component for astrocytic cell death following metabolic stress.

PMID- 22634250
TI  - Proteomic analysis of the brain tissues from a transgenic mouse model of amyloid
      beta oligomers.
AB  - Amyloid beta (Abeta) oligomers are presumed to be one of the causes of
      Alzheimer's disease (AD). Previously, we identified the E693Delta mutation in
      amyloid precursor protein (APP) in patients with AD who displayed almost no
      signals of amyloid plaques in amyloid imaging. We generated APP-transgenic mice
      expressing the E693Delta mutation and found that they possessed abundant Abeta
      oligomers from 8months of age but no amyloid plaques even at 24months of age,
      indicating that these mice are a good model to study pathological effects of
      Abeta oligomers. To elucidate whether Abeta oligomers affect proteome levels in
      the brain, we examined the proteins and phosphoproteins for which levels were
      altered in 12-month-old APP(E693Delta)-transgenic mice compared with age-matched
      non-transgenic littermates. By two-dimensional gel electrophoresis (2DE) followed
      by staining with SYPRO Ruby and Pro-Q Diamond and subsequent mass spectrometry
      techniques, we identified 17 proteins and 3 phosphoproteins to be significantly
      changed in the hippocampus and cerebral cortex of APP(E693Delta)-transgenic mice.
      Coactosin like-protein, SH3 domain-bind glutamic acid-rich-like protein 3 and
      astrocytic phosphoprotein PEA-15 isoform 2 were decreased to levels less than 0.6
      times those of non-transgenic littermates, whereas dynamin, profilin-2, vacuolar
      adenosine triphosphatase and creatine kinase B were increased to levels more than
      1.5 times those of non-transgenic littermates. Furthermore, 2DE Western Blotting
      validated the changed levels of dynamin, dihydropyrimidinase-related protein 2
      (Dpysl2), and coactosin in APP(E693Delta)-transgenic mice. Glyoxalase and
      isocitrate dehydrogenase were increased to levels more than 1.5 times those of
      non-transgenic littermates. The identified proteins could be classified into
      several groups that are involved in regulation of different cellular functions,
      such as cytoskeletal and their interacting proteins, energy metabolism, synaptic
      component, and vesicle transport and recycling. These findings indicate that
      Abeta oligomers altered the levels of some proteins and phosphoproteins in the
      hippocampus and cerebral cortex, which could illuminate novel therapeutic avenues
      for the treatment of AD.

PMID- 22634251
TI  - Private practice gastroenterology: challenges and opportunities.

PMID- 22634252
TI  - Immunotoxic and cytotoxic effects of atrazine, permethrin and piperonyl butoxide
      to rainbow trout following in vitro exposure.
AB  - For many current use pesticides, limited information exists on their cytotoxicity
      and immunotoxicity in non-target organisms such as fish. We examined the effects
      of atrazine, permethrin and piperonyl butoxide (PBO) exposure, in vitro, on
      rainbow trout (Oncorhynchus mykiss) lymphocyte viability and proliferation.
      Purified rainbow trout peripheral blood leukocytes (PBLs) were exposed in vitro
      to the test chemicals (0, 0.01, 0.1, 1 and 10 MUM) for 96 h, with and without the
      mitogen lipopolysaccharide. All three chemicals caused a decrease in both
      lymphocyte viability and proliferation at 10 MUM, while atrazine also suppressed
      proliferation of PBLs at 1 MUM. The in vitro toxicity of these chemicals to this
      salmonid underscores the need for further investigation using in vivo studies and
      host resistance models.

PMID- 22634253
TI  - Fish cell cultures as in vitro models of pro-inflammatory responses elicited by
      immunostimulants.
AB  - We have tested the elicitation of innate defence-related responses in two stromal
      cell lines derived from the spleen (trout splenic stroma, TSS) and the pronephros
      (trout pronephric stroma-2, TPS-2) of rainbow trout (Oncorhynchus mykiss) after
      they were exposed to different concentrations of lipopolysaccharide (LPS),
      levamisole, or polyinosinic polycytidylic acid (poly-I:C). For comparison,
      cultures of rainbow trout head kidney macrophages were also included in the
      study, and the effect of the immunostimulants on the phagocytic activity, the
      intracellular and extracellular reactive oxygen species and nitric oxide
      production were assayed. Although the responses varied depending upon the
      concentration of the immunostimulants and the particular cell line, our results
      demonstrate that those activities were enhanced in the TSS and TPS-2 cell lines
      after exposure to any of the immunostimulants. These results indicate that the
      stromal cells of the main lympho-haemopoietic organs of O. mykiss develop innate
      defence responses, which are enhanced by well-known immunostimulants. In
      addition, such enhancement of the defence responses in the TSS and TPS-2 cell
      lines could be also elicited when they were exposed to conditioned supernatants
      from levamisole- or poly I:C-stimulated HK macrophage cultures, thus
      demonstrating that the haemopoietic stromal cells respond to macrophage-derived
      factors. Moreover, we demonstrate that the stromal cell lines constitutively
      expressed the Toll-like receptors TLR3, TLR5 and TLR9 genes. The results are
      discussed considering the role of the lympho-haemopoietic stromal cells in the
      innate immune responses, and the possibility of using histiotypic cell cultures
      of non-leucocyte cells of the haemopoietic organs to develop in vitro methods to
      select new immunostimulant candidates for aquaculture.

PMID- 22634254
TI  - Molecular characterization of a novel tetraspanin from the oyster, Crassostrea
      ariakensis: variation, localization and relationship to oyster host defense.
AB  - We identified a tetraspanin family member gene, named Ca-TSP, in the oyster
      Crassostrea ariakensis and found that the transcription profiles of Ca-TSP were
      variable in the oyster hemocytes. Three distinct patterns of variation of Ca-TSP
      were observed. Using immunofluorescence and immunoelectron microscopy, we show
      that Ca-TSP was present in granules and in vesicular structures of the oyster
      hemocyte. Sequence analysis, structural features and immunogold electron
      microscopy showed that Ca-TSP is an integral membrane glycoprotein of granules of
      hemocyte and may be a novel CD63-like gene of the tetraspanin family of molluscs.
      The gene expression analysis of Ca-TSP using isolated oyster hemocytes, was done
      following challenge of the oysters with LPS and Poly I:C. The Ca-TSP mRNA levels
      increased in hemocytes in the first 12 h after LPS and Poly I:C stimulation, and
      decreased after the addition of H(2)O(2). Western blot analysis using anti-Ca-TSP
      antibody indicated that gene expression and protein levels were similar. The
      recombinant Ca-TSP was found to significantly inhibit hemocytes aggregation. Our
      results suggested that Ca-TSP participates in the innate immunity of the oyster.

PMID- 22634255
TI  - Effects of dietary Bacillus subtilis, Tetraselmis chuii, and Phaeodactylum
      tricornutum, singularly or in combination, on the immune response and disease
      resistance of sea bream (Sparus aurata L.).
AB  - Combined or individual effects of two microalgae (Phaeodactylum tricornutum and
      Tetraselmis chuii) and Bacillus subtilis on immune response, gene expression, and
      survival to challenge with Photobacterium damselae subsp. piscicida of gilthead
      sea bream were investigated. To test the capacity of B. subtilis to grow
      employing the microalgae polysaccharides as energy and carbon source, an in vitro
      assay was defined, and demonstrated that the digestion product of microalgae,
      mainly P. tricornutum, supported the growth of B. subtilis much better than
      glucose. For the in vivo study, fish were distributed in six equal groups (each
      of two replicates) and received one of the following experimental diets: C)
      control, non-supplemented diet; T) T. chuii 100 g kg(-1); P) P. tricornutum 100 g
      kg(-1); B) B. subtilis (10(7) cfu g(-1)); BT) B. subtilis (10(7) cfu g(-1))+T.
      chuii (100 g kg(-1)); and BP) B. subtilis (10(7) cfu g(-1))+P. tricornutum (100 g
      kg(-1)). The complement activity, serum IgM level, respiratory burst, phagocytic
      activity, and expression of seven selected immune-related genes in head-kidney
      were evaluated following two and four weeks of treatment. At the end of the
      feeding trial, fish were challenged by intraperitoneal injection of LD(50)
      concentration of P. damselae subsp. piscicida and mortality was recorded. This is
      the first study testing the immunomodulatory capacity of the microalgae used in
      the present work. The dietary applications of B. subtilis, T. chuii, and P.
      tricornutum, singly or in combination, may exhibit up-regulating effects on
      gilthead sea bream immune parameters. P. tricornutum demonstrated the highest
      immunostimulant activity. There were no significant differences between
      combination feeding and feeding ingredients separately. Our results demonstrated
      the potential of microalgae as immunostimulants for fish, although further
      studies regarding the implications and effects of a stimulated immune system
      against pathogens, especially the protective capacity against specific diseases,
      are necessary.

PMID- 22634256
TI  - Floral and vegetative cues in oil-secreting and non-oil-secreting Lysimachia
      species.
AB  - BACKGROUND AND AIMS: Unrelated plants pollinated by the same group or guild of
      animals typically evolve similar floral cues due to pollinator-mediated
      selection. Related plant species, however, may possess similar cues either as a
      result of pollinator-mediated selection or as a result of sharing a common
      ancestor that possessed the same cues or traits. In this study, visual and
      olfactory floral cues in Lysimachia species exhibiting different pollination
      strategies were analysed and compared, and the importance of pollinators and
      phylogeny on the evolution of these floral cues was determined. For comparison,
      cues of vegetative material were examined where pollinator selection would not be
      expected. METHODS: Floral and vegetative scents and colours in floral oil- and
      non-floral oil-secreting Lysimachia species were studied by chemical and
      spectrophotometric analyses, respectively, compared between oil- and non-oil
      secreting species, and analysed by phylogenetically controlled methods. KEY
      RESULTS: Vegetative and floral scent was species specific, and variability in
      floral but not vegetative scent was lower in oil compared with non-oil species.
      Overall, oil species did not differ in their floral or vegetative scent from non
      oil species. However, a correlation was found between oil secretion and six
      floral scent constituents specific to oil species, whereas the presence of four
      other floral compounds can be explained by phylogeny. Four of the five analysed
      oil species had bee-green flowers and the pattern of occurrence of this colour
      correlated with oil secretion. Non-oil species had different floral colours. The
      colour of leaves was similar among all species studied. CONCLUSIONS: Evidence was
      found for correlated evolution between secretion of floral oils and floral but
      not vegetative visual and olfactory cues. The cues correlating with oil secretion
      were probably selected by Macropis bees, the specialized pollinators of oil
      secreting Lysimachia species, and may have evolved in order to attract these
      bees.

PMID- 22634258
TI  - Advances in genetic engineering of marine algae.
AB  - Algae are a component of bait sources for animal aquaculture, and they produce
      abundant valuable compounds for the chemical industry and human health. With
      today's fast growing demand for algae biofuels and the profitable market for
      cosmetics and pharmaceuticals made from algal natural products, the genetic
      engineering of marine algae has been attracting increasing attention as a crucial
      systemic technology to address the challenge of the biomass feedstock supply for
      sustainable industrial applications and to modify the metabolic pathway for the
      more efficient production of high-value products. Nevertheless, to date, only a
      few marine algae species can be genetically manipulated. In this article, an
      updated account of the research progress in marine algal genomics is presented
      along with methods for transformation. In addition, vector construction and gene
      selection strategies are reviewed. Meanwhile, a review on the progress of
      bioreactor technologies for marine algae culture is also revisited.

PMID- 22634259
TI  - Correlation between CD16a binding and immuno effector functionality of an antigen
      specific immunoglobulin Fc fragment (Fcab).
AB  - Antigen binding immunoglobulin Fc fragments (Fcab) are generated by engineering
      loop regions in the CH3 domain of human IgG1 Fc. Variants of an Fcab specific for
      Her-2 were designed to display either enhanced (S239D:A330L:I332E) or diminished
      (L234A:L235A) binding affinities to the Fc receptor CD16a based on mutations
      described previously. The two mutant Fcab proteins demonstrated the expected
      modulation of CD16a binding. Interaction with recombinant or cell surface
      expressed Her-2 was unaffected in both mutants compared to the parental Fcab.
      Binding affinities for CD16a correlated with the ADCC-potencies of the Fcab
      variants. Additional studies indicated that the L234A:L235A variant Fcab had
      equivalent structural features as the unmodified Fcab since their DSC profiles
      were similar and antigen binding after re-folding upon partial heat denaturation
      had not changed. Introduction of the S239D:A330L:I332E mutations resulted in a
      significant reduction of the CH2 domain melting temperature, a moderate decrease
      of the thermal transition of the CH3 domain and lower antigen binding after
      thermal stress compared to the parental Fcab. We conclude that the known
      correlation between CD16a binding affinity and ADCC potency is also valid in Fcab
      proteins and that antigen specific Fcab molecules can be further engineered for
      fine tuning of immuno effector functions.

PMID- 22634257
TI  - Understanding the development of roots exposed to contaminants and the potential
      of plant-associated bacteria for optimization of growth.
AB  - BACKGROUND AND SCOPE: Plant responses to the toxic effects of soil contaminants,
      such as excess metals or organic substances, have been studied mainly at
      physiological, biochemical and molecular levels, but the influence on root system
      architecture has received little attention. Nevertheless, the precise position,
      morphology and extent of roots can influence contaminant uptake. Here, data are
      discussed that aim to increase the molecular and ecological understanding of the
      influence of contaminants on root system architecture. Furthermore, the potential
      of plant-associated bacteria to influence root growth by their growth-promoting
      and stress-relieving capacities is explored. METHODS: Root growth parameters of
      Arabidopsis thaliana seedlings grown in vertical agar plates are quantified.
      Mutants are used in a reverse genetics approach to identify molecular components
      underlying quantitative changes in root architecture after exposure to excess
      cadmium, copper or zinc. Plant-associated bacteria are isolated from contaminated
      environments, genotypically and phenotypically characterized, and used to test
      plant root growth improvement in the presence of contaminants. KEY RESULTS: The
      molecular determinants of primary root growth inhibition and effects on lateral
      root density by cadmium were identified. A vertical split-root system revealed
      local effects of cadmium and copper on root development. However, systemic
      effects of zinc exposure on root growth reduced both the avoidance of
      contaminated areas and colonization of non-contaminated areas. The potential for
      growth promotion and contaminant degradation of plant-associated bacteria was
      demonstrated by improved root growth of inoculated plants exposed to 2,4-di-nitro
      toluene (DNT) or cadmium. CONCLUSIONS: Knowledge concerning the specific
      influence of different contaminants on root system architecture and the molecular
      mechanisms by which this is achieved can be combined with the exploitation of
      plant-associated bacteria to influence root development and increase plant stress
      tolerance, which should lead to more optimal root systems for application in
      phytoremediation or safer biomass production.

PMID- 22634261
TI  - Euphol from Euphorbia tirucalli selectively inhibits human gastric cancer cell
      growth through the induction of ERK1/2-mediated apoptosis.
AB  - Gastric cancer is one of the most common malignancies worldwide, and the main
      cause of cancer-related death in Asia. The present study assessed the anticancer
      effects of euphol, a triterpene alcohol with anti-inflammatory and antiviral
      activities on human gastric cancer cells. Euphol showed higher cytotoxicity
      activity against human gastric CS12 cancer cells than against noncancer CSN
      cells. In addition, it up-regulated the pro-apoptotic protein BAX and down
      regulated the prosurvival protein Bcl-2, causing mitochondrial dysfunction,
      possibly by caspase-3 activation. The anti-proliferative effects of euphol were
      associated with the increased p27(kip1) levels and decreased cyclin B1 levels.
      Inhibition of ERK1/2 activation by PD98059 reversed euphol-induced pro-apoptotic
      protein expression and cell death. Taken together, these findings suggest that
      euphol selectively induced gastric cancer cells apoptosis by modulation of ERK
      signaling, and could thus be of value for cancer therapy.

PMID- 22634260
TI  - IgG-Fc glycoengineering in non-mammalian expression hosts.
AB  - The remarkable success of therapeutic applications of immunoglobulin G (IgG) in
      form of monoclonal antibodies and pooled immunoglobulin G preparations has
      directed attention to this class of glycoproteins. It is commonly appreciated
      that oligosaccharides attached to the Fc-region play a critical role in the
      biological activity of IgGs. Thus, glycosylation has been a focus of interest for
      many scientists and the biopharmaceutical industry and expression hosts have been
      engineered in order to optimize antibody products. In this review we focus on
      efforts towards a targeted manipulation of IgG-Fc N-glycans using non-mammalian
      expression hosts, i.e. yeast, insect cells and plants. Current achievements in
      generating human-like N-glycan structures will be presented and recent data on
      the molecular mechanisms that might explain how these potent drugs mediate in
      vivo activities will be discussed.

PMID- 22634262
TI  - Aqueous extract of Anisomeles indica and its purified compound exerts anti
      metastatic activity through inhibition of NF-kappaB/AP-1-dependent MMP-9
      activation in human breast cancer MCF-7 cells.
AB  - Anisomeles indica popularly known in Taiwan as 'yu-chen-tsao' has been
      traditionally used as an anticancer and anti-inflammatory agent; however, little
      is known about its anti-metastatic potential. Therefore, we attempted in this
      study to examine the anti-metastatic potential of A. indica aqueous extract (AI),
      its isolated compounds apigenin, ovatodiolide, beta-sitosterol and acteoside in
      12-O-tetradecanoylphorbol-13-acetate (TPA)-induced human breast adenocarcinoma
      MCF-7 cells. Among the test agents, crude extract AI and pure compound apigenin
      potently suppressed the TPA-induced MCF-7 cells migration and invasion. In
      addition, AI and apigenin time- and dose-dependently down regulated the matrix
      metalloproteinase (MMP)-9 enzymatic activities and its mRNA expression.
      Furthermore, AI and apigenin also down regulated the nuclear factor (NF)-kappaB
      subunit p65, and activator protein (AP)-1 subunit c-Fos proteins expression in
      nucleus and, transcriptional activity of NF-kappaB and AP-1. This is the first
      report on the anti-metastatic potential of A. indica that suppressed the cancer
      cell invasion through the inhibition of MMP-9 enzyme via NF-kappaB/AP-1
      signaling. Taken together, our data indicate that A. indica can be considered as
      a source of new anti-metastatic agent for food and pharmaceutical industries.

PMID- 22634263
TI  - Occurrence of aflatoxin M1 in raw milk collected from traditional dairies in
      Morocco.
AB  - A survey of the presence of aflatoxin M1 (AFM1) was carried out on eight
      traditional dairies belonging to four sectors of Fez city situated in the
      northern center of Morocco. Raw milk samples were collected between October 2009
      and September 2010, and analyzed by LC-fluorescence detection after
      immunoaffinity purification. AFM1 was detected in 13 out of 48 samples (27%) at
      concentrations ranged between 10 and 100 ng/l. Within these positive samples,
      four (~8% of the total) were above the European legislation limit of 50 ng/l.
      This study revealed a variation of contamination from one sector to another with
      a higher incidence in milk samples collected in autumn compared to those
      collected in other seasons suggesting a link between feeding practices, such as
      the use of silage and AFM1 contamination. This is the first report on AFM1
      contamination in raw milk directly collected from Moroccan traditional dairies.
      The levels of contamination found justify more detailed and continuous monitoring
      to assess the public health implication and reduce consumers' exposure to AFM1.

PMID- 22634264
TI  - Black cabbage seed extract affects rat Cyp-mediated biotransformation: organ and
      sex related differences.
AB  - Brassicaceae are widely consumed in many parts of the world and their dietary
      intake has been associated with cancer risk reduction. Extracts and metabolites
      derived from cruciferous vegetables have thus gained popularity as potential
      cancer chemopreventive agents. We have previously found, unexpectly, that
      glucoraphanin, the most extensively present glucosinolate in these vegetables, is
      a potent mutagen bioactivating Phase-I enzyme inducer. In the present study, the
      influence of black cabbage seed extract, rich in glucoraphanin, was investigated
      on Phase-I enzymes in different organs of male or female rats. Oral seed extract
      injection at 120 or 240 mg/kg b.w. for one or four consecutive days,
      significantly affected various cytochrome P450 (CYP) -linked monooxygenases in a
      complex way being the lung the most responsive organ (in males, up to ~2600%
      increase for CYP2B1/2 isoform and ~96% loss for CYP1A1, CYP3A1/2). These findings
      indicate that the extract may strongly enhance and/or suppress rat xenobiotic
      biotransformation pathways and that caution should be paid to the possible
      influence on human metabolism. These data suggest an overall evaluation of the
      balance between beneficial vs. possible adverse effects for each agent, even if
      of natural origin, prior to routinely, preventive mass use.

PMID- 22634265
TI  - The effects of sleep deprivation on the attentional functions and vigilance.
AB  - The study of sleep deprivation is a fruitful area of research to increase our
      knowledge of cognitive functions and their neural basis. In the current work, 26
      healthy young adults participated in a sleep deprivation study, in which the
      Attentional Networks Test for Interactions and Vigilance (ANTI-V) was performed
      at 10a.m. after a night of normal sleep and again at 10 a.m. after 25.5-27.5 h of
      total sleep deprivation. The ANTI-V is an experimental task that provides
      measures of alerting, orienting and executive control attentional functions.
      Compared with previous versions, the ANTI-V includes a vigilance task, more
      reliable auditory alerting signals, non-predictive peripheral orienting cues, and
      also a neutral no-cue condition allowing the analysis of reorienting costs and
      orienting benefits. Thus, new evidence to evaluate the influence of sleep
      deprivation on attentional functioning is provided. Results revealed differences
      in both tonic and phasic alertness after sleep deprivation. Vigilance performance
      was deteriorated, while a warning tone was more helpful to increase participants'
      alertness, resulting in slightly faster RT and, in particular, fewer errors. The
      reorienting costs of having an invalid spatial cue were reduced after sleep loss.
      No sleep deprivation effect on the executive control measure was found in this
      study. Finally, since no control group was used, particular precautions were
      taken to reduce the influence of potential practice effects.

PMID- 22634266
TI  - Four days later in Cincinnati: longitudinal tests of hyperbolic discounting.
AB  - Hyperbolic discounting of delayed rewards has been proposed as an underlying
      cause of the failure to stick to plans to forego one's immediate desires, such as
      the plan to diet, wake up early, or quit taking heroin. We conducted two tests of
      inconsistent planning in which respondents made at least two choices between a
      smaller-sooner (SS) and larger-later (LL) amount of money, one several weeks
      before SS would be received, and one immediately before. Hyperbolic discounting
      predicts that there would be more choices of SS as it became more proximate-and,
      equivalently, that among those who change their mind, "impatient shifts" (LL-to
      SS) will be more common than "patient shifts" (SS-to-LL). We find no evidence for
      this, however, and in our studies shifts in both directions were equally likely.
      We propose that some of the evidence cited on behalf of hyperbolic discounting
      can be attributed to qualitatively different psychological mechanisms.

PMID- 22634268
TI  - Balancing the tightrope of cardiac allograft rejection: equations or experience?

PMID- 22634267
TI  - Simple score to assess the risk of rejection after orthotopic heart
      transplantation.
AB  - BACKGROUND: The aim of this study was to derive and validate a risk score for
      rejection after orthotopic heart transplantation. METHODS AND RESULTS: The United
      Network for Organ Sharing registry was used to identify patients undergoing
      orthotopic heart transplantation between 1998 and 2008. A total of 14 265
      eligible patients were randomly divided into derivation (80%; n=11 412) and
      validation (20%; n=2853) cohorts. The primary outcome was drug-treated rejection
      within 1 year of orthotopic heart transplantation. Covariates found to be
      associated (exploratory univariate P<0.2) with rejection were entered into a
      multivariable logistic regression model. Inclusion of each variable in the model
      was assessed by improvement in the McFadden pseudo-R(2), likelihood ratio test,
      and c index. A risk score was then generated through the use of relative
      magnitudes of the odds ratios from the derivation cohort, and its ability to
      predict rejection was tested independently in the validation cohort. A 13-point
      risk score incorporating 4 variables (age, race, sex, HLA matching) was created.
      The mean scores in the derivation and validation cohorts were 8.3+/-2.2 and 8.4+/
      2.1, respectively. Predicted 1-year rejection rates based on the derivation
      cohort ranged from 16.2% (score=0) to 50.7% (score=13; P<0.001). In weighted
      regression analysis, there was a strong correlation between these predicted rates
      of rejection and actual, observed rejection rates in the validation cohort
      (r(2)=0.96, P<0.001). Logistic regression analysis also demonstrated a
      significant association (odds ratio, 1.13; P<0.001). The c index of the composite
      score was equivalent in both the derivation and validation cohorts (c=0.67).
      CONCLUSIONS: This novel 13-point risk score is highly predictive of clinically
      significant rejection episodes within 1 year of orthotopic heart transplantation.
      It has potential utility in tailoring immunosuppressive regimens and in research
      stratification in orthotopic heart transplantation.

PMID- 22634269
TI  - Electromyographic responses to emotional facial expressions in 6-7year olds: a
      feasibility study.
AB  - Preliminary studies have demonstrated that school-aged children (average age 9
      10years) show mimicry responses to happy and angry facial expressions. The aim of
      the present study was to assess the feasibility of using facial electromyography
      (EMG) as a method to study facial mimicry responses in younger children aged 6
      7years to emotional facial expressions of other children. Facial EMG activity to
      the presentation of dynamic emotional faces was recorded from the corrugator,
      zygomaticus, frontalis and depressor muscle in sixty-one healthy participants
      aged 6-7years. Results showed that the presentation of angry faces was associated
      with corrugator activation and zygomaticus relaxation, happy faces with an
      increase in zygomaticus and a decrease in corrugator activation, fearful faces
      with frontalis activation, and sad faces with a combination of corrugator and
      frontalis activation. This study demonstrates the feasibility of measuring facial
      EMG response to emotional facial expressions in 6-7year old children.

PMID- 22634270
TI  - Implicit affect primes effort: a theory and research on cardiovascular response.
AB  - This article introduces a new theory about implicit affect's influence on
      resource mobilization--the implicit-affect primes effort (IAPE) model--and
      discusses a series of experiments testing its predictions. The theory posits that
      affect primes (e.g., facial expressions or emotion words) implicitly activate
      mental representations of the respective affective states, containing information
      about ease and difficulty. This in turn influences the extent of subjective task
      demand during performance. A series of experiments assessing implicit affect's
      impact on effort-related cardiovascular response in cognitive tasks (especially
      cardiac pre-ejection period) supports this idea: (1) sadness primes processed
      during task performance led to stronger cardiovascular responses than both
      happiness and anger primes. (2) Affect primes moderated the effect of objective
      task difficulty: compared with sadness primes, both anger and happiness primes
      led to weaker response for easy tasks but to stronger response for difficult
      tasks. (3) The effort deficit of people primed with sadness during a difficult
      task could be compensated by high success incentive. Perspectives for future
      research on implicit affect and motivation are discussed.

PMID- 22634271
TI  - Interplay effects during Enhanced Dynamic Wedge deliveries.
AB  - In this study the interplay effects for Enhanced Dynamic Wedge (EDW) treatments
      are experimentally investigated. Single and multiple field EDW plans for
      different wedge angles were delivered to a phantom and detector on a moving
      platform, with various periods, amplitudes for parallel and perpendicular
      motions. A four field 4D CT planned lung EDW treatment was delivered to a dummy
      tumor over four fractions. For the single field parallel case the amplitude and
      the period of motion both affect the interplay resulting in the appearance of a
      step function and penumbral cut off with the discrepancy worst where collimator
      tumor speed is similar. For perpendicular motion the amplitude of tumor motion is
      the only dominant factor. For large wedge angle the dose discrepancy is more
      pronounced compared to the small wedge angle for the same field size and
      amplitude-period values. For a small field size i.e. 5 * 5 cm(2) the loss of
      wedged distribution was observed for both 60 degrees  and 15 degrees  wedge
      angles for parallel and perpendicular motions. Film results from 4D CT planned
      delivery displayed a mix of over and under dosages over 4 fractions, with the
      gamma pass rate of 40% for the averaged film image at 3%/1 mm DTA (Distance to
      Agreement). Amplitude and period of the tumor motion both affect the interplay
      for single and multi-field EDW treatments and for a limited (4 or 5) fraction
      delivery there is a possibility of non-averaging of the EDW interplay.

PMID- 22634272
TI  - Candida albicans infection inhibits macrophage cell division and proliferation.
AB  - The pathogenicity of the opportunistic human fungal pathogen Candida albicans
      depends on its ability to inhibit effective destruction by host phagocytes. Using
      live cell video microscopy, we show here for the first time that C. albicans
      inhibits cell division in macrophages undergoing mitosis. Inhibition of
      macrophage cell division is dependent on the ability of C. albicans to form
      hyphae, as it is rarely observed following phagocytosis of UV-killed or
      morphogenesis-defective mutant Candida. Interestingly, failed cell division
      following phagocytosis of hyphal C. albicans is surprisingly common, and leads to
      the formation of large multinuclear macrophages. This raises question as to
      whether inhibition of macrophage cell division is another virulence attribute of
      C. albicans or enables host macrophages to contain the pathogen.

PMID- 22634273
TI  - Functional analyses of regulators of G protein signaling in Gibberella zeae.
AB  - Regulators of G protein signaling (RGS) proteins make up a highly diverse and
      multifunctional protein family that plays a critical role in controlling
      heterotrimeric G protein signaling. In this study, seven RGS genes (FgFlbA,
      FgFlbB, FgRgsA, FgRgsB, FgRgsB2, FgRgsC, and FgGprK) were functionally
      characterized in the plant pathogenic fungus, Gibberella zeae. Mutant phenotypes
      were observed for deletion mutants of FgRgsA and FgRgsB in vegetative growth,
      FgFlbB and FgRgsB in conidia morphology, FgFlbA in conidia production, FgFlbA,
      FgRgsB, and FgRgsC in sexual development, FgFlbA and FgRgsA in spore germination
      and mycotoxin production, and FgFlbA, FgRgsA, and FgRgsB in virulence.
      Furthermore, FgFlbA, FgRgsA, and FgRgsB acted pleiotropically, while FgFlbB and
      FgRgsC deletion mutants exhibited a specific defect in conidia morphology and
      sexual development, respectively. Amino acid substitutions in Galpha subunits and
      overexpression of the FgFlbA gene revealed that deletion of FgFlbA and dominant
      active GzGPA2 mutant, gzgpa2(Q207L), had similar phenotypes in cell wall
      integrity, perithecia formation, mycotoxin production, and virulence, suggesting
      that FgFlbA may regulate asexual/sexual development, mycotoxin biosynthesis, and
      virulence through GzGPA2-dependent signaling in G. zeae.

PMID- 22634274
TI  - Biophysics of lipid bilayers containing oxidatively modified phospholipids:
      insights from fluorescence and EPR experiments and from MD simulations.
AB  - This review focuses on the influence of oxidized phosphatidylcholines (oxPCs) on
      the biophysical properties of model membranes and is limited to fluorescence,
      EPR, and MD studies. OxPCs are divided into two classes: A) hydroxy- or
      hydroperoxy-dieonyl phospatidylcholines, B) phospatidylcholines with oxidized and
      truncated chains with either aldehyde or carboxylic group. It was shown that the
      presence of the investigated oxPCs in phospholipid model membranes may have the
      following consequences: 1) decrease of the lipid order, 2) lowering of phase
      transition temperatures, 3) lateral expansion and thinning of the bilayer, 4)
      alterations of bilayer hydration profiles, 5) increased lipid mobility, 6)
      augmented flip-flop, 7) influence on the lateral phase organisation, and 8)
      promotion of water defects and, under extreme conditions (i.e. high
      concentrations of class B oxPCs), disintegration of the bilayer. The effects of
      class A oxPCs appear to be more moderate than those observed or predicted for
      class B. Many of the abovementioned findings are related to the ability of the
      oxidized chains of certain oxPCs to reorient toward the water phase. Some of the
      effects appear to be moderated by the presence of cholesterol. Although those
      biophysical alternations are found at oxPC concentrations higher than the total
      oxPC concentrations found under physiological conditions, certain organelles may
      reach such elevated oxPC concentrations locally. It is a challenge for the future
      to correlate the biophysics of oxidized phospholipids to metabolic studies in
      order to define the significance of the findings presented herein for
      pathophysiology. This article is part of a Special Issue entitled: Oxidized
      phospholipids-their properties and interactions with proteins.

PMID- 22634275
TI  - The DNA-DNA spacing in gemini surfactants-DOPE-DNA complexes.
AB  - Gemini surfactants from the homologous series of alkane-alpha,omega-diyl
      bis(dodecyldimethylammonium bromide) (CnCS12, number of spacer carbons n=2-12)
      and dioleoylphosphatidylethanolamine (DOPE) were used for cationic liposome (CL)
      preparation. CLs condense highly polymerized DNA creating complexes. Small-angle
      X-ray diffraction identified them as condensed lamellar phase L(alpha)(C) in the
      studied range of molar ratios CnGS12/DOPE in the temperature range 20-60 degrees
      C. The DNA-DNA distance (d(DNA)) is studied in dependence to CnGS12 spacer length
      and membrane surface charge density. The high membrane surface charge densities
      (CnGS12/DOPE=0.35 and 0.4mol/mol) lead to the linear dependence of d(DNA) vs. n
      correlating with the interfacial area of the CnGS12 molecule.

PMID- 22634276
TI  - In silico accelerated identification of structurally conserved CD8+ and CD4+ T
      cell epitopes in high-risk HPV types.
AB  - Primary approach to prevent cervical cancer includes the development of human
      papillomavirus (HPV) vaccines. Currently available HPV vaccines (Gardasil and
      Cervarix) predominantly consider HPV16 and HPV18 strains. However, due to
      ignorance of the other high-risk strains aside from HPV16 and HPV18 during
      vaccine development, the critical need is to synthesize a vaccine with possible
      protection against all the high-risk HPV types. One feasible approach is to
      design a vaccine containing conserved immunogenic peptides that represent the
      genotypic diversity of all the current and future high-risk HPV types. While the
      epitopes derived from sequentially conserved regions may undergo mutations, it is
      worthwhile to explore the structurally conserved regions as a new dimension for
      epitope prediction. In the present study, 81 structurally conserved peptides were
      predicted to have immune relevance as T-cell epitopes of all the reported high
      risk HPV proteins studied. A small dataset of three epitopes was also recognized
      as potential vaccine candidates generating both CD8+ and CD4+ responses.

PMID- 22634277
TI  - Molecular and phylogenetic analysis of bovine coronavirus based on the spike
      glycoprotein gene.
AB  - Bovine coronavirus has been associated with diarrhoea in newborn calves, winter
      dysentery in adult cattle and respiratory tract infections in calves and feedlot
      cattle. In Cuba, the presence of BCoV was first reported in 2006. Since then,
      sporadic outbreaks have continued to occur. This study was aimed at deepening the
      knowledge of the evolution, molecular markers of virulence and epidemiology of
      BCoV in Cuba. A total of 30 samples collected between 2009 and 2011 were used for
      PCR amplification and direct sequencing of partial or full S gene. Sequence
      comparison and phylogenetic studies were conducted using partial or complete S
      gene sequences as phylogenetic markers. All Cuban bovine coronavirus sequences
      were located in a single cluster supported by 100% bootstrap and 1.00 posterior
      probability values. The Cuban bovine coronavirus sequences were also clustered
      with the USA BCoV strains corresponding to the GenBank accession numbers EF424621
      and EF424623, suggesting a common origin for these viruses. This phylogenetic
      cluster was also the only group of sequences in which no recombination events
      were detected. Of the 45 amino acid changes found in the Cuban strains, four were
      unique.

PMID- 22634278
TI  - Morphometric and molecular evidence of intraspecific biogeographical
      differentiation of Rhodnius pallescens (HEMIPTERA: REDUVIIDAE: RHODNIINI) from
      Colombia and Panama.
AB  - Rhodnius pallescens is considered the main vector of Chagas disease in Panama and
      a relevant secondary vector in northern Colombia. Previous data reported that
      this species presents cytogenetically heterogeneous populations, which are
      probably biogeographically segregated. To provide new information on the
      diversity of R. pallescens, we compared several populations from Colombia and
      Panama based on the morphometric analyses of wings, mitochondrial cytochrome b
      (cyt b) gene sequencing, and genomic DNA measurements. Although no differences in
      DNA amount were detected, significant differences in cyt b sequences as well as
      wing size and shape were identified among populations. The results obtained in
      this work indicate R. pallescens comprises two evolutionary lineages with genetic
      and morphological differences that could be explained by their geographic
      isolation in distinct ecological zones. These results provide new insight into R.
      pallescens population diversity and the underlying biological processes that
      shape its evolution.

PMID- 22634279
TI  - A sigh following sustained attention and mental stress: effects on respiratory
      variability.
AB  - Normal breathing consists of considerable correlated variability (parameters of
      subsequent breaths are correlated) and some random variability. Emotional and
      attentive states alter normal breathing variability, which can be restored by a
      sigh. The present study aimed to investigate the effects of mental arithmetic and
      sustained attention on respiratory variability. In addition, the effect of a
      spontaneous sigh following both conditions was examined, compared to an
      instructed sigh and a control maneuver. Mental arithmetic and sustained attention
      were characterized by decreased correlated and total breathing variability,
      respectively. A spontaneous sigh restored correlated variability. An instructed
      sigh restored correlated variability following mental arithmetic, and increased
      total variability following sustained attention. These results suggest that a
      spontaneous sigh and an instructed sigh, when physiologically appropriate,
      restore respiratory variability influenced by stress or attention.

PMID- 22634280
TI  - Paternal responsiveness is associated with, but not mediated by reduced neophobia
      in male California mice (Peromyscus californicus).
AB  - Hormones associated with pregnancy and parturition have been implicated in
      facilitating the onset of maternal behavior via reductions in neophobia, anxiety,
      and stress responsiveness. To determine whether the onset of paternal behavior
      has similar associations in biparental male California mice (Peromyscus
      californicus), we compared paternal responsiveness, neophobia (novel-object
      test), and anxiety-like behavior (elevated plus maze, EPM) in isolated virgins
      (housed alone), paired virgins (housed with another male), expectant fathers
      (housed with pregnant pairmate), and new fathers (housed with pairmate and pups).
      Corticotropin-releasing hormone (CRH) and Fos immunoreactivity (IR) were
      quantified in brain tissues following exposure to a predator-odor stressor or
      under baseline conditions. New fathers showed lower anxiety-like behavior than
      expectant fathers and isolated virgins in EPM tests. In all housing conditions,
      stress elevated Fos-IR in the hypothalamic paraventricular nucleus (PVN). Social
      isolation reduced overall (baseline and stress-induced) Fos- and colocalized
      Fos/CRH-IR, and increased overall CRH-IR, in the PVN. In the central nucleus of
      the amygdala, social isolation increased stress-induced CRH-IR and decreased
      stress-induced activation of CRH neurons. Across all housing conditions,
      paternally behaving males displayed more anxiety-related behavior than
      nonpaternal males in the EPM, but showed no differences in CRH- or Fos-IR.
      Finally, the latency to engage in paternal behavior was positively correlated
      with the latency to approach a novel object. These results suggest that being a
      new father does not reduce anxiety, neophobia, or neural stress responsiveness.
      Low levels of neophobia, however, were associated with, but not necessary for
      paternal responsiveness.

PMID- 22634281
TI  - The effects of a high-energy diet on hippocampal-dependent discrimination
      performance and blood-brain barrier integrity differ for diet-induced obese and
      diet-resistant rats.
AB  - Rats that consume high-energy (HE) diets (i.e., diets high in saturated fats and
      sugar) show impaired hippocampal-dependent learning and memory (e.g., Kanoski and
      Davidson (2011) [1]). To further investigate this effect, we trained rats given
      restricted access to low-fat lab chow on hippocampal-dependent serial feature
      negative (FN) and hippocampal-independent simple discrimination problems. When
      training was completed, Group Chow received ad libitum lab chow. The remaining
      rats received ad libitum HE diet. Performance on both discrimination problems was
      tested following 7, 14, 21 and 28 days of HE diet exposure. FN, but not simple
      discrimination, was abolished initially for all rats, and then re-emerged for
      Group Chow. For rats fed HE diet, those that weighed the least and had the lowest
      amount of body fat (HE-diet resistant (HE-DR) rats), performed like Group Chow on
      both discrimination problems. However, HE diet-induced obese (HE-DIO) rats (i.e.,
      rats that weighed the most weight and had the most body fat) performed like Group
      Chow on the simple discrimination problem, but were impaired throughout testing
      on the FN problem. Subsequent assessment of blood-brain barrier (BBB)
      permeability revealed that concentrations of an exogenously administered dye were
      elevated in the hippocampus, but not in the striatum or prefrontal cortex for HE
      DIO rats relative to the HE-DR and Chow groups. The results indicate that the
      adverse consequences of HE diet on hippocampal-dependent cognitive functioning
      are associated with detrimental effects on the BBB and that both of these
      outcomes vary with sensitivity to HE diet-induced increases in weight and
      adiposity.

PMID- 22634282
TI  - Real-time evidence for EF-G-induced dynamics of helix 44 in 16S rRNA.
AB  - The penultimate stem-loop of 16S ribosomal RNA (rRNA), helix 44, plays a central
      role in ribosome function. Using time-resolved dimethyl sulfate (DMS) probing, we
      have analyzed time-dependent modifications that occur at specific bases in this
      helix near the decoding region, resulting from the binding of elongation factor G
      (EF-G) in various forms. When EF-G-GTP is bound to 70S ribosomes, bases A1492 and
      A1493 are immediately protected, while other bases in the region show either no
      change or enhanced modification. When apo-EF-G is bound to 70S ribosomes and GTP
      is added, substantial transient time-dependent enhancement occurs at bases A1492
      and A1493, with somewhat less enhancement occurring at base A1483, all in the
      first 45 ms. When mRNA and deacylated tRNAs are bound to the 70S ribosome and EF
      G-GTP is added, bases A1492 and A1493 again show substantial and continued
      enhancement, while bases A1408, A1413, and A1418 all show time-dependent
      protection. These results provide primary, real-time evidence that EF-G induces
      direct or indirect structural changes in this region as EF-G is bound and as GTP
      is hydrolyzed.

PMID- 22634283
TI  - Biophysical basis of the binding of WWOX tumor suppressor to WBP1 and WBP2
      adaptors.
AB  - The WW-containing oxidoreductase (WWOX) tumor suppressor participates in a
      diverse array of cellular activities by virtue of its ability to recognize WW
      binding protein 1 (WBP1) and WW-binding protein 2 (WBP2) signaling adaptors among
      a wide variety of other ligands. Herein, using a multitude of biophysical
      techniques, we provide evidence that while the WW1 domain of WWOX binds to PPXY
      motifs within WBP1 and WBP2 in a physiologically relevant manner, the WW2 domain
      exhibits no affinity toward any of these PPXY motifs. Importantly, our data
      suggest that while R25/W44 residues located within the binding pocket of a triple
      stranded beta-fold of WW1 domain are critical for the recognition of PPXY
      ligands, they are replaced by the chemically distinct E66/Y85 duo at structurally
      equivalent positions within the WW2 domain, thereby accounting for its failure to
      bind PPXY ligands. Predictably, not only does the introduction of E66R/Y85W
      double substitution within the WW2 domain result in gain of function but the
      resulting engineered domain, hereinafter referred to as WW2_RW, also appears to
      be a much stronger binding partner of WBP1 and WBP2 than the wild-type WW1
      domain. We also show that while the WW1 domain is structurally disordered and
      folds upon ligand binding, the WW2 domain not only adopts a fully structured
      conformation but also aids stabilization and ligand binding to WW1 domain. This
      salient observation implies that the WW2 domain likely serves as a chaperone to
      augment the physiological function of WW1 domain within WWOX. Collectively, our
      study lays the groundwork for understanding the molecular basis of a key protein
      protein interaction pertinent to human health and disease.

PMID- 22634284
TI  - Crystallographically mapped ligand binding differs in high and low IgE binding
      isoforms of birch pollen allergen bet v 1.
AB  - The ability of pathogenesis-related proteins of family 10 to bind a broad
      spectrum of ligands is considered to play a key role for their physiological and
      pathological functions. In particular, Bet v 1, an archetypical allergen from
      birch pollen, is described as a highly promiscuous ligand acceptor. However, the
      detailed recognition mechanisms, including specificity factors discriminating
      binding properties of naturally occurring Bet v 1 variants, are poorly
      understood. Here, we report crystal structures of Bet v 1 variants in complex
      with an array of ligands at a resolution of up to 1.2 A. Residue 30 within the
      hydrophobic pocket not only discriminates in high and low IgE binding Bet v 1
      isoforms but also induces a drastic change in the binding mode of the model
      ligand deoxycholate. Ternary crystal structure complexes of Bet v 1 with several
      ligands together with the fluorogenic reporter 1-anilino-8-naphthalene sulfonate
      explain anomalous fluorescence binding curves obtained from 1-anilino-8
      naphthalene sulfonate displacement assays. The structures reveal key interaction
      residues such as Tyr83 and rationalize both the binding specificity and
      promiscuity of the so-called hydrophobic pocket in Bet v 1. The intermolecular
      interactions of Bet v 1 reveal an unexpected complexity that will be
      indispensable to fully understand its roles within the physiological and
      allergenic context.

PMID- 22634285
TI  - Lack of ethical approval and omission of experimental evidence.

PMID- 22634286
TI  - Allografting ovarian cortex between genetically non-identical sisters: authors'
      correction (Donnez et al.).

PMID- 22634287
TI  - Allografting ovarian cortex between genetically non-identical sisters: authors'
      correction (Englert et al.).

PMID- 22634288
TI  - The Brown Norway opticospinal model of demyelination: does it mimic multiple
      sclerosis or neuromyelitis optica?
AB  - Opticospinal demyelinating diseases in humans are mostly characterized by the
      opticospinal form of multiple sclerosis (MS) and neuromyelitis optica (NMO).
      Increasing attention has recently focused on astrocyte markers, aquaporin-4
      (AQP4) and glial fibrillary acidic protein (GFAP) in these diseases. We induced
      opticospinal demyelination in Brown Norway rats with soluble recombinant rat
      myelin oligodendrocyte glycoprotein (1-116) and incomplete Freund's adjuvant.
      Clinical, MRI, neuropathological and immunological evaluations were performed,
      with a focus on AQP4 and GFAP. We confirmed the opticospinal phenotype, including
      extensive myelitis, but also showed the MRI-characterized involvement of the
      periventricular area. Expression levels of myelin, AQP4 and GFAP showed the early
      involvement of astrocytes before demyelination in the optic nerve. The
      overexpression of AQP4 was particularly pronounced in the spinal cord and was
      concomitant with demyelination and astrocyte apoptosis. The disability scores
      were correlated with demyelination and inflammation but not with AQP4/GFAP
      expression. No antibodies against the linear and conformational epitopes of AQP4
      were detected. Whereas a NMO-like phenotype was observed in this model, the
      AQP4/GFAP expression during the disease process was more closely related to
      opticospinal MS than NMO. However, this model raises the question of a continuum
      between opticospinal MS and the seronegative NMO subtype.

PMID- 22634289
TI  - Protective role of propolis in chlorpyrifos-induced changes in the haematological
      parameters and the oxidative/antioxidative status of Cyprinus carpio carpio.
AB  - The protective effect of propolis on haematological parameters and antioxidant
      status were evaluated in the blood and various tissues of carp exposed to
      chlorpyrifos (CPF). The fish were exposed to sublethal concentrations of CPF
      (0.040 and 0.080 mg/L) for 10 days, and propolis (10 mg per kg of fish weight)
      was simultaneously administered. Samples of the blood and tissue (liver, kidney,
      and gill) were collected at the end of the experiment and analysed for their
      oxidant-antioxidant status, including the malondialdehyde (MDA) levels, and the
      superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)
      activity. The samples were also measured for changes in the haematological
      parameters, such as the red blood cell (RBC) and white blood cell (WBC) counts,
      the haemoglobin concentration (Hb), the haematocrit (Ht) level, and the
      erythrocyte indices: the mean corpuscular volume (MCV), the mean corpuscular
      haemoglobin (MCH) and the mean corpuscular haemoglobin concentration (MCHC). The
      findings of this study demonstrated that CPF had a negative effect on the
      haematological parameters and the antioxidant enzyme activities of the fish; this
      toxic effect was neutralised by the administration of propolis. The present
      results suggest that propolis can be effective in the protection of CPF-induced
      toxicity in fish.

PMID- 22634290
TI  - Reactive oxygen species mediated ginsenoside Rg3- and Rh2-induced apoptosis in
      hepatoma cells through mitochondrial signaling pathways.
AB  - Panax ginseng (P. ginseng) has anti-cancer effects in several cancer models.
      Ginsenosides are the main bioactive components in P. ginseng. Korean red ginseng
      (KRG) extract can potently kill various cancer cells and ginsenosides Rg3 (GRg3)
      and Rh2 (GRh2) are the primary ginsenosides in KRG. This study was carried out to
      examine whether KRG and its primary ginsenosides (GRg3 and GRh2) affect apoptosis
      of human hepatocellular carcinoma cells (Hep3B). KRG, GRg3 and GRh2 have obvious
      cytotoxic and apoptotic effects in Hep3B cells as evidenced by a decrease in cell
      viability and mitochondria membrane potential, but an increase in LDH release. In
      the mitochondria-mediated apoptosis pathway, KRG, GRg3 and GRh2 have the ability
      to stimulate the release of mitochondrial cytochrome c, activation of caspase-3
      and Bax protein, inhibition of Bcl-2 protein and production of intracellular
      reactive oxygen species in Hep3B cells. These results suggest that KRG, GRg3 and
      GRh2 may induce apoptosis by direct activation of the mitochondrial pathway.

PMID- 22634291
TI  - Mercury and selenium in fish and shellfish: occurrence, bioaccessibility and
      uptake by Caco-2 cells.
AB  - This study evaluates Hg and Se concentrations and bioaccessibility (element
      solubilised after simulated gastrointestinal digestion) in 16 raw seafood species
      consumed in Spain. The concentrations varied greatly (Hg, 3.8-1621 ng/g wet
      weight, ww; Se, 84-1817 ng/g ww). Only one sample of swordfish exceeded the Hg
      limit permitted in Spain (1mg/kg), and for this sample the Hg/Se molar ratio and
      Se Health Benefit Value food safety criteria also indicated the presence of a
      risk. Bioaccessibility of Hg (35-106%) and Se (17-125%) was very variable and the
      Hg/Se molar ratio in the bioaccessible fraction was less than one for all
      samples. Transport by Caco-2 cells, an intestinal epithelium model, was also
      evaluated from the swordfish bioaccessible fraction. Hg and Se transport from the
      food was less than 14%, and cell retention was much greater for Hg (49-69%) than
      Se (8-12%).

PMID- 22634292
TI  - Multisensory speech perception without the left superior temporal sulcus.
AB  - Converging evidence suggests that the left superior temporal sulcus (STS) is a
      critical site for multisensory integration of auditory and visual information
      during speech perception. We report a patient, SJ, who suffered a stroke that
      damaged the left tempo-parietal area, resulting in mild anomic aphasia.
      Structural MRI showed complete destruction of the left middle and posterior STS,
      as well as damage to adjacent areas in the temporal and parietal lobes.
      Surprisingly, SJ demonstrated preserved multisensory integration measured with
      two independent tests. First, she perceived the McGurk effect, an illusion that
      requires integration of auditory and visual speech. Second, her perception of
      morphed audiovisual speech with ambiguous auditory or visual information was
      significantly influenced by the opposing modality. To understand the neural basis
      for this preserved multisensory integration, blood-oxygen level dependent
      functional magnetic resonance imaging (BOLD fMRI) was used to examine brain
      responses to audiovisual speech in SJ and 23 healthy age-matched controls. In
      controls, bilateral STS activity was observed. In SJ, no activity was observed in
      the damaged left STS but in the right STS, more cortex was active in SJ than in
      any of the normal controls. Further, the amplitude of the BOLD response in right
      STS response to McGurk stimuli was significantly greater in SJ than in controls.
      The simplest explanation of these results is a reorganization of SJ's cortical
      language networks such that the right STS now subserves multisensory integration
      of speech.

PMID- 22634293
TI  - Comparative validity of accelerometer-based measures of physical activity for
      people with multiple sclerosis.
AB  - OBJECTIVE: To estimate the criterion validity of accelerometer-based devices as
      measures of steps and energy expenditure in healthy controls and people with
      multiple sclerosis (MS) with varying disability levels during everyday
      activities. DESIGN: Cross-sectional study. SETTING: University research room.
      PARTICIPANTS: People with MS who used at most a stick to walk outdoors (MS-A;
      n=19), people with MS who used bilateral support for gait (MS-B; n=11), and
      healthy controls (n=15). INTERVENTIONS: Participants completed 85 minutes of 9
      scripted everyday activities. MAIN OUTCOME MEASURES: Estimates of metabolic
      equivalent thresholds (METs) and kilocalories from a portable metabolic system,
      and steps counted from video of the activities. Step and MET estimates from an
      integrative accelerometer and from a uniaxial accelerometer, and kilocalorie
      estimates from the integrative accelerometer. RESULTS: The uniaxial accelerometer
      had >30% error for steps for all groups. MET estimates had an intraclass
      correlation coefficient (ICC) <0.2 for all groups. For the integrative
      accelerometer, step estimates for controls had an ICC of .69 and <1% error. The
      step estimates for MS-A and MS-B groups had >20% error. The MET estimates had an
      ICC of .50 to .65 and 6% to 15% error. Kilocalorie estimates had 2.9% error for
      controls, 8.16% for MS-A, and 2.56% for MS-B groups. ICCs were all >.67, and mean
      differences from criterion were <20kcal. CONCLUSIONS: The agreement between steps
      and MET estimates from both devices and the criterion was poor, particularly for
      people with MS. Only the step and MET estimates for the control group for the
      integrative accelerometer were not significantly different from the criterion.
      Kilocalorie estimates from the integrative accelerometer using the proprietary
      algorithms of the device provide the most valid estimate of physical activity
      during activities of daily living for people with a range of walking disabilities
      resulting from MS.

PMID- 22634294
TI  - Waning population immunity to measles in Taiwan.
AB  - To evaluate the population immunity to measles in Taiwan where the coverage rate
      of the measles vaccine was >95% for more than a decade, anti-measles IgG was
      determined in 3552 Taiwanese volunteers in 2007. The overall seroprevalence was
      74.7% (95% confidence interval [CI]: 73.3-76.1%). In subgroups aged 2-25 years,
      to whom at least 2 doses of measles-containing vaccine were given, there was a
      declining trend of seropositivity with age from 94.5% at 2 years to 50.6% at 21
      25 years (p<0.0001). Age (odds ratio [OR]: 1.0464, 95% CI: 1.043-1.085) and male
      gender (OR: 1.466, 95% CI: 1.131-1.901) were independent factors predicting
      seronegative sera in this population. Seroprevalence was uniformly >95% in the
      older population (>= 35 years) who had not been immunized against measles. The
      waning vaccine-induced immunity may have impact on the control of measles in the
      future, especially when the vaccinated population becomes older.

PMID- 22634295
TI  - A totally synthetic lipopeptide-based self-adjuvanting vaccine induces
      neutralizing antibodies against heat-stable enterotoxin from enterotoxigenic
      Escherichia coli.
AB  - ST-based lipopeptide vaccine candidates were constructed in which ST was
      chemically synthesized and folded into the correct conformation prior to ligation
      to a module containing a T-helper cell epitope (T(H)) and the Toll-like receptor
      2 (TLR2) agonist, S-[2,3-bis(palmitoyloxy)propyl]cysteine (P2C). Two different
      chemistries, thioether-based and oxime-based, were then used to ligate ST to the
      lipidated T(H) epitope. The enterotoxic activity of synthetic ST and the ST-based
      lipopeptide vaccines was determined in mice followed by an evaluation of
      immunological efficacy. The importance of the fine detail in chemical composition
      used in vaccine design was demonstrated by the findings that (i) the oxime-based
      vaccine exhibited little or no toxicity but the thioether-based vaccine,
      exhibited residual toxicity in suckling mice, (ii) although each of the synthetic
      vaccines generated specific anti-ST antibodies, it was the low titer antibodies
      induced by the oxime-based vaccine that demonstrated better neutralizing activity
      suggesting that the chemical linkage also affects the specificity of antibodies,
      (iii) the geometric arrangement of ST within a vaccine can profoundly affect the
      specificity and biological function of the antibodies that are elicited, and (iv)
      the lipopeptide-based ST vaccine candidate assembled using oxime chemistry
      induced a better neutralizing antibody response to ST when administered by the
      mucosal (intranasal) route.

PMID- 22634297
TI  - Human and animal rabies prevention and control cost in Bhutan, 2001-2008: the
      cost-benefit of dog rabies elimination.
AB  - The objective of this study was to estimate the cost of various interventions and
      to quantify the economic impacts of rabies in Bhutan. Cost-benefit of dog rabies
      elimination versus human post exposure treatment cost was also assessed. The
      average direct medical cost of human post-exposure treatment (using rabies
      vaccine only) was estimated to be Nu. 1615 (US$ 35.65) per 5-dose Essen regimen
      per patient. The cost would increase to Nu. 2497 (US$ 55.13) and Nu. 19,633 (US$
      433.41) per patient when one dose of either equine rabies immunoglobulin (ERIG)
      or human rabies immunoglobulin (HRIG) is administered, respectively. The societal
      cost (direct medical and indirect patient expenses) per patient was estimated to
      be Nu. 2019 (US$ 45), Nu. 2901 (US$ 64) and Nu. 20,037 (US$ 442) using vaccine
      only, vaccine with ERIG and vaccine with HRIG, respectively. The average cost per
      dog vaccination and sterilization were estimated to be Nu. 75 (US$ 1.66) and Nu.
      288 (US$ 6.36), respectively. The total direct cost of rabies and various
      interventions between 2001 and 2008 was estimated to be Nu. 46.95 million (US$
      1.03 million). The direct cost for intensified human PET was estimated to be Nu.
      5.85 million (US$ 0.11 million) per year with a cumulated estimated costs of Nu.
      35.10 million (US$ 0.70 million) while the cost of mass dog vaccination with at
      least 70% coverage is estimated to be approximately Nu. 10.31 million (US$ 0.21
      million) at the end of 6 years. The combined cost of mass dog vaccination and
      human PET was estimated to be greater than the cost of human PET alone during the
      first 2 years of the campaign, and then would be lower than human PET cost alone
      after the 5th year of the campaign. The total cumulated cost of the combined
      strategy was estimated to be Nu. 34.14 million (US$ 0.73 million) and would be
      lower than the cumulated cost of human PET alone (Nu. 35.10 million, US$ 0.77
      million) at the end of 6 years. Rabies represents a substantial economic impact
      to the Bhutanese society. Well-planned and implemented mass dog vaccination would
      result in elimination of rabies reservoirs in the domestic dog population and
      would eliminate human rabies cases. It would also reduce the recurrent
      expenditure on human post-exposure treatment.

PMID- 22634296
TI  - Fine specificity and cross-reactions of monoclonal antibodies to group B
      streptococcal capsular polysaccharide type III.
AB  - Group B streptococcus (GBS) is a major cause of neonatal sepsis and meningitis.
      Despite aggressive campaigns using antenatal prophylactic antibiotic therapy,
      infections continue. Developing an effective maternal vaccine is a public health
      priority. Antibody (Ab) to the capsular polysaccharide (CPS) is considered the
      dominant "protective" immune mediator. Here we study the fine specificity and
      potential host reactivity of a panel of well-characterized murine monoclonal Abs
      against the type III CPS by examining the binding of the Abs to intact and
      neuraminidase-digested GBS, purified CPS, synthetic carbohydrate structures, and
      cells. The results showed marked differences in the fine specificity among these
      mAbs to a single carbohydrate structure. Cross-reactions with synthetic GD3 and
      GT3 carbohydrates, representing structures found on surfaces of neural and
      developing cells, were demonstrated using carbohydrate array technology. The anti
      CPS(III) mAbs did not react with cells expressing GD3 and GT3, nor did mAbs
      specific for the host carbohydrates cross-react with GBS, raising questions about
      the physiological relevance of this cross-reaction. But in the process of these
      investigations, we serendipitously demonstrated cross-reactions of some anti
      CPS(III) mAbs with antigens, likely carbohydrates, found on human leukocytes.
      These studies suggest caution in the development of a maternal vaccine to prevent
      infection by this important human pathogen.

PMID- 22634298
TI  - Toll-like receptor 3 agonist complexed with cationic liposome augments vaccine
      elicited antitumor immunity by enhancing TLR3-IRF3 signaling and type I
      interferons in dendritic cells.
AB  - Cancer vaccine-based immunotherapy is emerging as a novel therapeutic strategy
      for cancer treatment. However, its antitumor effect remains unsatisfied due to
      the poor immunogenicity of tumor antigens (Ags). Although polyriboinosinic:
      polyribocytidylic acid (PIC), a TLR3 agonist, has been reported as a promising
      adjuvant for cancer vaccines, its immunopotency may be limited by insufficient
      cellular penetration. In the present study, we incorporated PIC into DOTAP
      cationic liposome to generate PIC-DOTAP Liposome Complex (PDLC) nanoparticles.
      The results showed that PDLC was more potent than DOTAP or PIC to enhance vaccine
      induced tumor-specific cytotoxic T lymphocyte (CTL) response and IFN-gamma
      production. Moreover, two doses of PDLC vaccines remarkably suppressed tumor
      growth in mice, which involved the participance of CD8(+) T cells and depended on
      the presence of Ag. The superior antitumor effect of PDLC vaccines could be
      attributable to enhanced maturation of mouse bone-marrow dendritic cells (BMDCs)
      and increased production of type I IFNs. More importantly, PDLC strengthened the
      TLR3 signaling in BMDCs by enhancing the interaction of PIC with TLR3 and
      augmenting downstream IRF-3 phosphorylation, as well as elevating IRF-3/IRF-7
      mRNA transcription. Taking together, the complex of PIC and DOTAP liposomes
      enhanced PIC uptake and consequential TLR3 signaling in BMDCs, which in turn
      promoted DC maturation and type I IFN production, thereby augmenting the
      antitumor effect of cancer vaccines.

PMID- 22634299
TI  - Immunoprotective activity of a Salmonid Alphavirus Vaccine: comparison of the
      immune responses induced by inactivated whole virus antigen formulations based on
      CpG class B oligonucleotides and poly I:C alone or combined with an oil adjuvant.
AB  - CpG oligonucleotides and polyinosinic:polycytidylic acid (poly I:C) are toll-like
      receptor (TLR) agonists that mimic the immunostimulatory properties of bacterial
      DNA and double-stranded viral RNA respectively, and which have exhibited
      potential to serve as vaccine adjuvants in previous experiments. Here, a
      combination of CpGs and poly I:C together with water- or oil-formulated Salmonid
      Alphavirus (SAV) antigen preparations has been used for a vaccine in Atlantic
      salmon and tested for protection in SAV challenge trial. The results demonstrate
      that vaccination with a high dose of the SAV antigen induced protection against
      challenge with SAV which correlated with production of neutralizing antibodies
      (NAbs). As the high antigen dose alone induced full protection, no beneficial
      effect from the addition of CpG and poly I:C could be observed. Nevertheless,
      these TLR ligands significantly enhanced the levels of NAbs in serum of
      vaccinated fish. Interestingly, gene expression analysis demonstrated that while
      addition of oil suppressed the CpG/poly I:C-induced expression of IFN-gamma, the
      upregulation of IFNa1 was substantially enhanced. A low dose of the SAV antigen
      combined with oil did not induce any detectable levels of NAbs either with or
      without TLR ligands present, however the addition of CpG and poly I:C to the low
      SAV antigen dose formulation significantly enhanced the protection against SAV
      suggesting that CpG/poly I:C may have enhanced a cytotoxic response - a process
      which is dependent on the up-regulation of type I IFN. These results highlight
      the immunostimulatory properties of the tested TLR ligands and will serve as a
      ground for further, more detailed studies aimed to investigate their capacity to
      serve as adjuvants in vaccine formulations for Atlantic salmon.

PMID- 22634300
TI  - Recombinant retrovirus-derived virus-like particle-based vaccines induce
      hepatitis C virus-specific cellular and neutralizing immune responses in mice.
AB  - While the immunological correlates of hepatitis C virus (HCV)-specific immunity
      are not well understood, it is now admitted that an effective vaccine against HCV
      will need to induce both cellular and humoral immune responses and address viral
      heterogeneity to prevent immune escape. We developed a vaccine platform
      specifically aimed at inducing such responses against HCV antigens displayed by
      recombinant retrovirus-based virus-like particles (VLPs) made of Gag of murine
      leukemia virus. Both ex vivo produced VLPs and plasmid DNA encoding VLPs can be
      used as vaccines. Here, we report that immunizations with plasmid DNA forming
      VLPs pseudotyped with HCV E1 and E2 envelope glycoproteins (HCV-specific plasmo
      retroVLPs) induce strong T-cell-mediated immune responses that can be optimized
      by using proper DNA delivery methods and/or genetic adjuvants. Additionally,
      multigenotype or multi-specific T-cell responses were observed after immunization
      with plasmids that encode VLPs pseudotyped with E1E2 derived from numerous viral
      genotypes and/or displaying NS3 antigen in capsid proteins. While homologous
      prime-boost immunizations with HCV-specific plasmo-retroVLPs or ex vivo produced
      VLPs induce a low level of specific antibody responses, optimal combination of
      plasmo-retroVLPs and VLPs was identified for inducing HCV-specific T-cell and B
      cell responses as well as neutralizing antibodies. Altogether, these results have
      important meanings for the development of anti-HCV preventive vaccines and
      exemplify the flexibility and potential of our retrovirus-based platform in
      inducing broad cellular and humoral immune responses.

PMID- 22634301
TI  - Use of virtual screening for discovering antiretroviral compounds interacting
      with the HIV-1 nucleocapsid protein.
AB  - The HIV-1 nucleocapsid protein (NC) is considered as an emerging drug target for
      the therapy of AIDS. Several studies have highlighted the crucial role of NC
      within the viral replication cycle. However, although NC inhibition has provided
      in vitro and in vivo antiretroviral activity, drug-candidates which interfere
      with NC functions are still missing in the therapeutic arsenal against HIV. Based
      on previous studies, where the dynamic behavior of NC and its ligand binding
      properties have been investigated by means of computational methods, here we used
      a virtual screening protocol for discovering novel antiretroviral compounds which
      interact with NC. The antiretroviral activity of virtual hits was tested in
      vitro, whereas biophysical studies elucidated the direct interaction of most
      active compounds with NC(11-55), a peptide corresponding to the zinc finger
      domain of NC. Two novel antiretroviral small molecules capable of interacting
      with NC are presented here.

PMID- 22634302
TI  - Regulation of hepatitis C virus translation initiation by iron: role of eIF3 and
      La protein.
AB  - Eukaryotic initiation factors (eIFs) are required for encoding polyprotein of
      hepatitis C virus (HCV) which is mediated by an internal ribosome-entry site
      (IRES). Iron overload, a common finding among HCV patients, may be correlated
      with HCV pathology, but the underlying molecular mechanisms are poorly
      understood. In this study, we investigated the possible relationship among iron
      status, eIFs and HCV IRES-mediated translation in vitro. Using bicistronic
      reporter gene constructs carrying HCV IRES sequence, we found that the levels of
      intracellular iron were positively associated with the HCV IRES-dependent
      translation initiation in Huh-7 cells. RT-PCR method showed that iron treatment
      specifically increased the levels of eIF3A mRNA and La mRNA, whereas iron
      chelation reduced them. Western blots also confirmed that iron-dependent changes
      in eIF3A mRNA and La mRNA affected the expression of their proteins. Moreover,
      antisense phosphorothioate oligodeoxynucleotides to eIF3A and La successfully
      suppressed the levels of eIF3A and La protein and significantly reduced iron
      dependent HCV translation. Taken together, our results suggest that iron promotes
      the translation initiation of HCV by stimulating the expression of eIF3A and La
      proteins. Inhibition of eIF3A and La proteins substantially repressed iron
      dependent HCV translation, a beneficial effect that may have significant clinical
      implications.

PMID- 22634303
TI  - Pro-inflammatory and immunomodulatory functions of airway smooth muscle: emerging
      concepts.
AB  - Airway smooth muscle (ASM) is the main regulator of bronchomotor tone. Extensive
      studies show that in addition to their physical property, human airway smooth
      muscle (ASM) cells can participate in inflammatory processes modulating the
      initiation, perpetuation, amplification, and perhaps resolution of airway
      inflammation. Upon stimulation or interaction with immune cells, ASM cells
      produce and secrete a variety of inflammatory cytokines and chemokines, cell
      adhesion molecules, and extracellular matrix (ECM) proteins. These released
      mediators can, in turn, contribute to the inflammatory state, airway
      hyperresponsiveness, and airway remodeling present in asthma. As our knowledge of
      ASM myocyte biology improves, novel bioactive factors are emerging as potentially
      important regulators of inflammation. This review provides an overview of our
      understanding of some of these molecules, identifies rising questions, and
      proposes future studies to better define their role in ASM cell modulation of
      inflammation and immunity in the lung and respiratory diseases.

PMID- 22634304
TI  - Cigarette smoke-induced inflammation and respiratory host defense: Insights from
      animal models.
AB  - While the devastating impact of tobacco on human health is well established, and
      efforts to reduce its prevalence are ongoing, over 1 billion people continue to
      smoke. Emerging evidence suggests that cigarette smoking distorts lung immune
      homeostasis, compromising respiratory host defense. Consequently, viral and
      bacterial agents are dealt with inefficiently and are associated with exaggerated
      immune inflammatory responses. In this article, we discuss mechanisms by which
      cigarette smoke elicits inflammatory processes and how smoking impacts
      respiratory host defense against viral and bacterial agents. Elucidating
      cigarette smoke's impacts on lung immune homeostasis will contribute to our
      understanding of the pathogenesis of chronic obstructive pulmonary disease COPD.

PMID- 22634306
TI  - Single-chain variable fragment intrabody impairs LPS-induced inflammatory
      responses by interfering with the interaction between the WASP N-terminal domain
      and Btk in macrophages.
AB  - Wiskott-Aldrich syndrome protein (WASP) plays important roles in both acquired
      and innate immune responses. We recently uncovered that the WASP N-terminal
      domain specifically binds the Src homology (SH) 3 domain of Bruton's tyrosine
      kinase (Btk) in macrophages. Over-expression of the WASP N-terminal domain
      impairs LPS-induced inflammatory responses. To evaluate the significance of this
      interaction in LPS signaling, we established bone marrow-derived macrophage
      (BMDM) cell lines from transgenic (Tg) mice expressing anti-WASP N-terminal
      domain single-chain variable fragment (scFv) intrabody. Anti-WASP scFv
      specifically bound endogenous WASP and inhibited its specific binding to the SH3
      domain of Btk in the Tg BMDMs. Tyrosine phosphorylation in WASP was inhibited
      after LPS stimulation. As a result, TNF-alpha, IL-6, and IL-1beta gene
      transcription and NF-kappaB phosphorylation were impaired. These observations
      strongly suggest that the phosphorylation of WASP by Btk plays a pivotal role in
      transducing the LPS signaling pathway in macrophages.

PMID- 22634305
TI  - Obesity and respiratory infections: does excess adiposity weigh down host
      defense?
AB  - The number of overweight and obese individuals has dramatically increased in the
      US and other developed nations during the past 30 years. While type II diabetes
      and cardiovascular disease are well recognized co-morbid conditions associated
      with obesity, recent reports have demonstrated a greater severity of illness in
      obese patients due to influenza during the 2009 H1N1 pandemic. Consistent with
      these reports, diet-induced obesity has been shown to impair anti-viral host
      defense in murine models of influenza infection. However, the impact of obesity
      on the risk of community-acquired and nosocomial pneumonia in human patients is
      not clear. Relatively few studies have evaluated the influence of diet-induced
      obesity in murine models of bacterial infections of the respiratory tract. Obese
      leptin deficient humans and leptin and leptin-receptor deficient mice exhibit
      greater susceptibility to respiratory infections suggesting a requirement for
      leptin in the pulmonary innate and adaptive immune response to infection. In
      contrast to these studies, we have observed that obese leptin receptor signaling
      mutant mice are resistant to pneumococcal pneumonia highlighting the complex
      interaction between leptin receptor signaling and immune function. Given the
      increased prevalence of obesity and poor responsiveness of obese individuals to
      vaccination against influenza, the development of novel immunization strategies
      for this population is warranted. Additional clinical and animal studies are
      needed to clarify the relationship between increased adiposity and susceptibility
      to community-acquired and nosocomial pneumonia.

PMID- 22634307
TI  - Characterization of human lung cancer-associated fibroblasts in three-dimensional
      in vitro co-culture model.
AB  - Lung cancer is the most common cause of cancer-related death worldwide. Stromal
      cancer-associated fibroblasts (CAFs) play crucial roles in carcinogenesis,
      proliferation, invasion, and metastasis of non-small cell lung carcinoma, and
      targeting of CAFs could be a novel strategy for cancer treatment. However, the
      characteristics of human CAFs still remain to be better defined. In this study,
      we established patient-matched CAFs and normal fibroblasts (NFs), from tumoral
      and non-tumoral portions of resected lung tissue from lung cancer patients. CAFs
      showed higher alpha-smooth muscle actin (alpha-SMA) expression than NFs, and CAFs
      clearly enhanced collagen gel contraction. Furthermore, we employed three
      dimensional co-culture assay with A549 lung cancer cells, where CAFs were more
      potent in inducing collagen gel contraction. Hematoxylin and eosin staining of co
      cultured collagen gel revealed that CAFs had the potential to increase invasion
      of A549 cells compared to NFs. These observations provide evidence that lung CAFs
      have the tumor-promoting capacity distinct from NFs.

PMID- 22634308
TI  - Marked over expression of uncoupling protein-2 in beta cells exerts minor effects
      on mitochondrial metabolism.
AB  - Evidence is conflicting as to the impact of elevated levels of uncoupling protein
      2 (UCP-2) on insulin-producing beta cells. Here we investigated effects of a
      fourfold induction of UCP-2 protein primarily on mitochondrial parameters and
      tested for replication of positive findings at a lower level of induction. We
      transfected INS-1 cells to obtain a tet-on inducible cell line. A 48 h exposure
      to 1 MUg/ml of doxycycline (dox) induced UCP-2 fourfold (424 +/- 113%, mean+/
      SEM) and 0.1 MUg/ml twofold (178 +/- 29%, n=3). Fourfold induced cells displayed
      normal viability (MTT, apoptosis), normal cellular insulin contents and, glucose
      induced insulin secretion (+27 +/- 11%) as well as D-[U-(14)C]-glucose oxidation
      (+5 +/- 9% at 11 mM glucose). Oxidation of [1-(14)C]-oleate was increased from
      4088 to 5797 fmol/MUg prot/2h at 3.3mM glucose, p<0.03. Oxidation of L-[(14)C(U)]
      glutamine was unaffected. Induction of UCP-2 did not significantly affect
      measures of mitochondrial membrane potential (Rhodamine 123) or mitochondrial
      mass (Mitotracker Green) and did not affect ATP levels. Oligomycin-inhibited
      oxygen consumption (a measure of mitochondrial uncoupling) was marginally
      increased, the effect being significant in comparison with dox-only treated
      cells, p<0.05. Oxygen radicals, assessed by dichlorofluorescin diacetate, were
      decreased by 30%, p<0.025. Testing for the lower level of UCP-2 induction did not
      reproduce any of the positive findings. A fourfold induction of UCP-2 was
      required to exert minor metabolic effects. These findings question an impact of
      moderately elevated UCP-2 levels in beta cells as seen in diabetes.

PMID- 22634309
TI  - EBF1 acts as a powerful repressor of Blimp-1 gene expression in immature B cells.
AB  - The transcription factor, early B cell factor 1 (EBF1) with an atypical zinc
      finger and helix-loop-helix motif, is essential for development and
      differentiation of lymphocytes. In mice, EBF1 is involved in the generation of
      pre-pro B cells (the first specified progenitors of B cells) from common lymphoid
      progenitors (CLPs) and transcription regulations of various genes involved in B
      cell-development, for instance, mb-1 and Pax5. During B lymphopoiesis,
      interestingly, EBF1 is detected throughout from CLPs to mature B cells. However,
      in immature B cells, the physiological role of EBF1 remains to be elucidated.
      Here, by analyzing EBF1-deficient DT40 cells, EBF1(-/-), generated by us, we show
      that EBF1-deficiency caused significant increases (to ~800%) in both mRNA and
      protein levels of B lymphocyte-induced maturation protein-1 (Blimp-1), the master
      gene for plasma cell differentiation. In addition, both transcription and protein
      synthesis of Blimp-1 were remarkably down-regulated (to ~20%) by re-expression
      (over-expression) of EBF1. Chromatin immunoprecipitation assay revealed that EBF1
      binds to proximal 5'-upstream regions around two putative EBF1 binding motifs of
      the gene in vivo. These results suggest that EBF1 takes part in transcriptional
      regulations of the Blimp-1 gene in immature B cells, and may play a key role in B
      cell differentiation. This is the first report on a novel EBF1 function in
      immature B cells as a powerful repressor of Blimp-1 gene expression.

PMID- 22634310
TI  - Curative and protective effects of L-arginine on carbon tetrachloride-induced
      hepatotoxicity in mice.
AB  - L-arginine may aid in the liver detoxification and may benefit in the treatment
      of liver disorders such as liver injury. The present study was to investigate the
      possible protective and curative effects of L-arginine on carbon tetrachloride
      (CCl(4)) induced hepatotoxicity. Mice received a single dose of CCl(4). L
      arginine treatment was given for 6 days prior or post to CCl(4) injection. CCl(4)
      intoxication caused marked liver cell necrosis with inflammatory and apoptotic
      lesions. L-arginine treatment reduced hepatic necrosis and inflammation. CCl(4)
      intoxication also enhanced hepatic lipid peroxidation, decreased hepatic GSH
      level and inhibited the activities of antioxidant enzymes. Pre-treatment and post
      treatment with L-arginine decreased lipid peroxidation and restored the
      antioxidant status to near normal levels. These results suggest that L-arginine
      administration has hepatoprotective and hepatocurative effects against CCl(4)
      induced hepatotoxicity in mice.

PMID- 22634311
TI  - Effects of hydrogen peroxide in a keratinocyte-fibroblast co-culture model of
      wound healing.
AB  - Recently, there has been renewed interest in the role of reactive oxygen species
      (ROS), especially H(2)O(2), in wound healing. We previously showed that H(2)O(2)
      stimulates healing in a keratinocyte scratch wound model. In this paper, we used
      a more complex and physiologically relevant model that involves co-culturing
      primary keratinocytes and fibroblasts. We found that the two main cell types
      within the skin have different sensitivities to H(2)O(2) and to the widely used
      "antioxidant"N-acetyl-l-cysteine (NAC). Keratinocytes were very resistant to the
      toxicity of H(2)O(2) (250 and 500 MUM) or NAC (5 mM). However, the viability of
      fibroblasts was decreased by both compounds. Using the co-culture model, we also
      found that H(2)O(2) increases re-epithelialization while NAC retards it. Our data
      further illustrate the possible role of ROS in wound healing and the co-culture
      model should be useful for screening agents that may influence the wound healing
      process.

PMID- 22634312
TI  - Identification and functional characterization of human glycerol-3-phosphate
      acyltransferase 1 gene promoters.
AB  - Glycerol-3-phosphate acyltransferase 1 (GPAT1) acts as a rate limiting enzyme in
      triacylglycerol and phospholipid synthesis in mammals. GPAT1 regulates hepatic
      lipid accumulation associated with metabolic disorders. Here we have identified
      two transcriptional initiation sites and two promoters (promoter I and II)
      required for expression of the human GPAT1 (hGPAT1) gene. Promoter I regulates
      transcription of three alternative hGPAT1 mRNA variants, hGPAT1-V1, V2, and V3,
      while promoter II induces expression of a fourth variant, hGPAT1-V4. RT-PCR
      analysis and luciferase reporter assays revealed that promoter II acts in
      lipogenic tissues like the liver (and liver-derived HepG2 cells), whereas
      promoter I is differentially regulated and also acts in non-liver HeLa cells.
      Among liver-enriched transcription factors, HNF4alpha and C/EBPalpha slightly
      activated hGPAT1 promoter I, while factors including HNF1alpha altered promoter
      II activity. The lipogenic transcription factor SREBP1c greatly increased
      promoter II activity in HepG2 cells. The use of various truncated or mutated
      fragments of promoter II revealed that one sterol regulatory element-like motif
      and one inverted CCAAT box on promoter II contributed to the SREBP1c response.
      These cis-acting elements and trans-acting factors can be potential targets for
      manipulation of hepatic GPAT1 levels in humans.

PMID- 22634313
TI  - A novel adipocytokine, chemerin exerts anti-inflammatory roles in human vascular
      endothelial cells.
AB  - Chemerin is a recently identified adipocytokine which plays a role on
      inflammation and adipocytes metabolism. However, its function in vasculature is
      largely unknown. We examined the effects of chemerin on vascular endothelial
      inflammatory states. Treatment of human umbilical vein endothelial cells with
      chemerin (300 ng/ml, 20 min) induced phosphorylation of Akt (Ser473) and
      endothelial nitric oxide (NO) synthase (eNOS) (Ser1177). Consistently, chemerin
      increased intracellular cyclic GMP content. Pretreatment with chemerin (1-300
      ng/ml, 24 h) significantly inhibited phosphorylation of nuclear factor (NF)
      kappaB p65 (Ser536) and p38 as well as vascular cell adhesion molecule (VCAM)-1
      expression induced by tumor necrosis factor (TNF)-alpha (5 ng/ml, 20 min-6 h).
      Inhibitor of NF-kappaB or p38 significantly inhibited the TNF-alpha-induced VCAM
      1 expression. Chemerin also inhibited TNF-alpha-induced VCAM-1 expression in rat
      isolated aorta. Moreover, chemerin significantly inhibited monocytes adhesion to
      TNF-alpha-stimulated endothelial cells. The inhibitory effect of chemerin on TNF
      alpha-induced VCAM-1 was reversed by a NOS inhibitor. Conversely, an NO donor,
      sodium nitroprusside significantly inhibited TNF-alpha-induced VCAM-1. The
      present results for the first time demonstrate that chemerin plays anti
      inflammatory roles by preventing TNF-alpha-induced VCAM-1 expression and
      monocytes adhesion in vascular endothelial cells. The effect is mediated via
      inhibiting activation of NF-kappaB and p38 through stimulation of Akt/eNOS
      signaling and NO production.

PMID- 22634314
TI  - Forced expression of stabilized c-Fos in dendritic cells reduces cytokine
      production and immune responses in vivo.
AB  - Intracellular cyclic adenosine monophosphate (cAMP) suppresses innate immunity by
      inhibiting proinflammatory cytokine production by monocytic cells. We have shown
      that the transcription factor c-Fos is responsible for cAMP-mediated suppression
      of inflammatory cytokine production, and that c-Fos protein is stabilized by
      IKKbeta-mediated phosphorylation. We found that S308 is one of the major
      phosphorylation sites, and that the S308D mutation prolongs c-Fos halflife. To
      investigate the role of stabilized c-Fos protein in dendritic cells (DCs) in
      vivo, we generated CD11c-promoter-deriven c-FosS308D transgenic mice. As
      expected, bone marrow-derived DCs (BMDCs) from these Tg mice produced smaller
      amounts of inflammatory cytokines, including TNF-alpha, IL-12, and IL-23, but
      higher levels of IL-10, in response to LPS, than those from wild-type (Wt) mice.
      When T cells were co-cultured with BMDCs from Tg mice, production of Th1 and Th17
      cytokines was reduced, although T cell proliferation was not affected. Tg mice
      demonstrated more resistance to experimental autoimmune encephalomyelitis (EAE)
      than did Wt mice. These data suggest that c-Fos in DCs plays a suppressive role
      in certain innate and adaptive immune responses.

PMID- 22634315
TI  - Epigenetic loss of CDH1 correlates with multidrug resistance in human
      hepatocellular carcinoma cells.
AB  - Promoter CpG hypermethylation of tumor suppressor genes is an essential step in
      cancer progression but little is known about its effect on cancer multidrug
      resistance. In this study, we showed that CDH1 promoter was hypermethylated in
      drug resistance of a doxorubicin-induced multidrug resistant hepatocellular
      carcinoma cell line R-HepG2. Transfection of CDH1 cDNA into R-HepG2 cells led to
      increased amount of doxorubicin uptake, decreased cell viability, decreased P
      glycoprotein expression and increased apoptotic population of cells exposed to
      doxorubicin. Proto-oncogene tyrosine-protein kinase FYN was over-expressed in R
      HepG2 cells which displayed a negative correlation with the expression of CDH1.
      FYN was knocked down in R-HepG2 cells, leading to less drug resistance by
      increased cell viability, increased doxorubicin uptake and attenuated P
      glycoprotein expression. Our findings identified epigenetic silencing of CDH1 in
      cancer cells might be a new molecular event of multidrug resistance.

PMID- 22634316
TI  - Lung epithelial-C/EBPbeta contributes to LPS-induced inflammation and its
      suppression by formoterol.
AB  - The inflammatory processes associated with pulmonary disorders remains
      incompletely understood. CCAAT/enhancer-binding protein (C/EBP)beta is implicated
      in inflammatory lung disorders as well as in beta(2)-adrenoceptor signaling. We
      hypothesized that C/EBPbeta in the lung epithelium contributes to
      lipopolysaccharide (LPS)-induced airway neutrophilia and expression of neutrophil
      chemoattractant chemokine (C-X-C) motif ligand (CXCL)1, as well as the
      suppressive effects of long-acting beta(2)-agonists (LABAs) and glucocorticoids
      (GCs). To investigate this, mice with a lung epithelial-specific deletion of
      C/EBPbeta (Cebpb(DeltaLE)) and control littermates (Cebpb(fl/fl)) were pre
      treated with a LABA, formoterol and/or a GC, budesonide, and challenged with LPS.
      Inflammatory cell recruitment in bronchoalveolar lavage (BAL) fluid and pulmonary
      expression of inflammatory mediators were investigated. In addition, the ability
      of formoterol to increase C/EBP transactivation was assessed in vitro. LPS
      challenged Cebpb(DeltaLE) mice exhibited fewer BAL neutrophils and lower
      pulmonary expression of CXCL1 versus Cebpb(fl/fl) mice. Suppression of LPS
      induced neutrophilia by formoterol was impaired in Cebpb(DeltaLE) mice and Cxcl1
      expression was increased. However, suppression of the neutrophilia by budesonide
      with/without formoterol was preserved. Further studies indicated that C/EBP
      transactivation was increased by the cAMP elevating agent forskolin and
      formoterol in a beta(2)-adrenoceptor dependent manner. Thus, C/EBPbeta in the
      lung epithelium contributes to LPS-induced CXCL1 expression and airway
      neutrophilia as well as to the suppressive effects of formoterol. Reduced
      C/EBPbeta activity, observed in smokers with chronic obstructive pulmonary
      disease, may impair the responsiveness to LABAs when used without GCs.

PMID- 22634317
TI  - Histone deacetylase is required for the activation of Wnt/beta-catenin signaling
      crucial for heart valve formation in zebrafish embryos.
AB  - During vertebrate heart valve formation, Wnt/beta-catenin signaling induces BMP
      signals in atrioventricular canal (AVC) myocardial cells and underlying AVC
      endocardial cells then undergo endothelial-mesenchymal transdifferentiation (EMT)
      by receiving this BMP signals. Histone deacetylases (HDACs) have been implicated
      in numerous developmental processes by regulating gene expression. However, their
      specific roles in controlling heart valve development are largely unexplored. To
      investigate the role of HDACs in vertebrate heart valve formation, we treated
      zebrafish embryos with trichostatin A (TSA), an inhibitor of class I and II
      HDACs, from 36 to 48 h post-fertilization (hpf) during which heart looping and
      valve formation occur. Following TSA treatment, abnormal linear heart tube
      development was observed. In these embryos, expression of AVC myocardial bmp4 and
      AVC endocardial notch1b genes was markedly reduced with subsequent failure of EMT
      in the AVC endocardial cells. However, LiCl-mediated activation of Wnt/beta
      catenin signaling was able to rescue defective heart tube formation, bmp4 and
      notch1b expression, and EMT in the AVC region. Taken together, our results
      demonstrated that HDAC activity plays a pivotal role in vertebrate heart tube
      formation by activating Wnt/beta-catenin signaling which induces bmp4 expression
      in AVC myocardial cells.

PMID- 22634318
TI  - Exploring the effect of different plant lignin content and composition on ionic
      liquid pretreatment efficiency and enzymatic saccharification of Eucalyptus
      globulus L. mutants.
AB  - There are several approaches being investigated to improve the efficiency of
      biomass conversion into fermentable sugars, including those that engineer the
      feedstocks to enhance digestibility. In this study it was evaluated the impact of
      genotype modifications of three mutants of Eucalyptus globulus L., and of the
      corresponding wild type on cellulose hydrolyzability before and after ionic
      liquid (IL) pretreatment. Both untreated and IL-treated samples were chemically
      characterized and tested for cellulose hydrolizability. Results obtained indicate
      that genetic modifications altered wood lignin-S/G ratio. This alteration
      resulted in a different hydrolyzability of cellulose for untreated samples, i.e.
      high lignin-S/G ratio produced low glucose yield (r=-0.97; P<0.03; n=4), but did
      not affect glucose yield after IL pretreatment. IL pretreated samples had
      increased glucose yields compared to that of untreated samples due to the
      modification of microcrystalline cellulose I to mixtures of more hydrolysable
      cellulose II and amorphous cellulose, and to the partial removal of the steric
      impediment, or removal of the lignin "sheath" protecting cellulose, to enzymes.
      The efficiency of the IL pretreatment used in this study does not appear to be
      affected by the S/G content of the E. globulus.

PMID- 22634320
TI  - Comparative meta-analysis of the effect of Lactobacillus species on weight gain
      in humans and animals.
AB  - BACKGROUND: Obesity is associated with alteration of the gut microbiota. In order
      to clarify the effect of Lactobacillus-containing probiotics (LCP) on weight we
      performed a meta-analysis of clinical studies and experimental models. We
      intended to assess effects by Lactobacillus species. METHODS: A broad search with
      no date or language restriction was performed. We included randomized controlled
      trials (RCTs) and comparative clinical studies in humans and animals or
      experimental models assessing the effect of Lactobacillus-containing probiotics
      on weight. We primarily attempted to extract and use change from baseline values.
      Data were extracted independently by two authors. Results were pooled by host and
      by Lactobacillus species and are summarized in a meta-analysis of standardized
      difference in means (SMDs). RESULTS: We identified and included 17 RCTs in
      humans, 51 studies on farm animals and 14 experimental models. Lactobacillus
      acidophilus administration resulted in significant weight gain in humans and in
      animals (SMD 0.15; 95% confidence intervals 0.05-0.25). Results were consistent
      in humans and animals. Lactobacillus fermentum and Lactobacillus ingluviei were
      associated with weight gain in animals. Lactobacillus plantarum was associated
      with weight loss in animals and Lactobacillus gasseri was associated with weight
      loss both in obese humans and in animals. CONCLUSIONS: Different Lactobacillus
      species are associated different effects on weight change that are host-specific.
      Further studies are needed to clarify the role of Lactobacillus species in the
      human energy harvest and weight regulation. Attention should be drawn to the
      potential effects of commonly marketed lactobacillus-containing probiotics on
      weight gain.

PMID- 22634319
TI  - A phase I first-in-human trial of bardoxolone methyl in patients with advanced
      solid tumors and lymphomas.
AB  - PURPOSE: Bardoxolone methyl, a novel synthetic triterpenoid and antioxidant
      inflammation modulator, potently induces Nrf2 and inhibits NF-kappaB and Janus
      activated kinase/STAT signaling. This first-in-human phase I clinical trial aimed
      to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD),
      and appropriate dose for phase II studies; characterize pharmacokinetic and
      pharmacodynamic parameters; and assess antitumor activity. EXPERIMENTAL DESIGN:
      Bardoxolone methyl was administered orally once daily for 21 days of a 28-day
      cycle. An accelerated titration design was employed until a grade 2-related
      adverse event occurred. A standard 3 + 3 dose escalation was then employed until
      the MTD was reached. Single dose and steady-state plasma pharmacokinetics of the
      drug were characterized. Assessment of Nrf2 activation was examined in peripheral
      blood mononuclear cells (PBMC) by measuring NAD(P)H:quinone oxidoreductase (NQO1)
      mRNA levels. Immunohistochemical assessment of markers of inflammation, cell
      cycle, and apoptosis was carried out on tumor biopsies. RESULTS: The DLTs were
      grade 3 reversible liver transaminase elevations. The MTD was established as 900
      mg/d. A complete tumor response occurred in a mantle cell lymphoma patient, and a
      partial response was observed in an anaplastic thyroid carcinoma patient. NQO1
      mRNA levels increased in PBMCs, and NF-kappaB and cyclin D1 levels decreased in
      tumor biopsies. Estimated glomerular filtration rate (eGFR) was also increased.
      CONCLUSIONS: Bardoxolone methyl was well tolerated with an MTD of 900 mg/d. The
      increase in eGFR suggests that bardoxolone methyl might be beneficial in chronic
      kidney disease. Objective tumor responses and pharmacodynamic effects were
      observed, supporting continued development of other synthetic triterpenoids in
      cancer.

PMID- 22634321
TI  - Understanding and correcting for carbon nanotube interferences with a commercial
      LDH cytotoxicity assay.
AB  - The lactate dehydrogenase (LDH) assay accurately quantifies cytotoxicity of
      chemicals via the measurement of LDH released from damaged cells. In the assay,
      LDH catalyzes formation of a reporter chromophore that can be quantified
      spectrophotometrically at its 490 nm peak, a standard assay, and related to the
      released LDH concentration. However, certain engineered nanomaterials have been
      reported to produce aberrant values, resulting in inaccurate assessment of
      toxicity as measured by LDH levels in media. We studied this effect
      spectroscopically by measuring unexpected changes in the complete visible
      spectrum of the product chromophore resulting from using either purified LDH or
      LDH from lysed cells in the presence of varying concentrations of single walled
      carbon nanotubes (SWCNTs) or carbon nanohorns (SWCNH-oxs). Basically, at constant
      LDH concentrations, the 490 nm product peak decreased with increasing carbon
      nanotube concentration, while the 580 nm peak increased to a lesser extent and
      the maximum absorbing wavelength increased. The product chromophore spectrum was
      altered in different ways by potential interactions with a number of components
      in the reaction mixture including: BSA, LDH, SWCNTs, SWCNT-oxs, or various
      combinations of these species. We propose to improve the accuracy of the LDH
      assay when evaluated in the presence of varying concentrations of these carbon
      nanostructures by use of both the 490 and 580 nm peak absorbances combined via
      regression analysis. Our results indicate that molecular probes of cytotoxicity
      must be assessed individually for accuracy in the presence of engineered
      nanomaterials.

PMID- 22634322
TI  - Tumor necrosis factor-alpha mediates interactions between macrophages and
      epithelial cells underlying proinflammatory gene expression induced by
      particulate matter.
AB  - Ambient particulate matter (PM) exposure is known to have adverse effects on
      respiratory health, but the underlying mechanisms remain obscure. We tested the
      hypothesis that macrophages and epithelial cells synergize to produce maximal
      cytokine release in response to PM exposure, thereby promoting inflammatory
      responses. We developed a co-culture model using MLE-12 (mouse lung epithelial)
      cells and RAW 264.7 (mouse monocyte/macrophage) cells. MLE-12 cells produced KC
      (Cxcl1) but not tumor necrosis factor-alpha (TNF), and KC was upregulated only at
      high levels of urban particulate matter (UPM; NIST 1648a). RAW 264.7 cells
      produced TNF but not KC, and TNF production was increased by treatment with UPM.
      In contrast, KC production was upregulated by co-culture of MLE-12 and RAW 264.7
      cells, and it was further increased by treatment with a concentration of UPM that
      had no effect on MLE-12 cells alone. Multiplex cytokine assay revealed a similar
      pattern of synergistic production of MIG (Cxcl9) and IP-10 (Cxcl10) in co
      cultures in response to UPM. TNF was implicated as mediating the synergistic
      increase in KC production because TNF upregulated KC production in MLE-12 cells,
      and UPM-induced KC production in co-cultures could be inhibited by a TNF blocking
      antibody. Intratracheal instillation of UPM into both wild-type and TNF receptor
      knockout mice resulted in increased TNF production in lavage fluid and increased
      TNF mRNA expression in cells recovered from lavage fluid. Additionally, UPM
      instillation into wild-type mice resulted in increased neutrophils and KC in
      lavage fluid, and these were inhibited in UPM-exposed TNF receptor knockout mice.
      These results are consistent with a model in which PM activates TNF production in
      macrophages which in turn stimulates epithelial cells to produce proinflammatory
      cytokines such as KC. The findings suggest a potential mechanism by which inhaled
      PM induces inflammation in the lung.

PMID- 22634323
TI  - Immunological studies on glycated human IgG.
AB  - AIMS: To study the immunogenicity of advanced glycation end product (AGE)
      modified IgG (AGE-IgG) in experimental animals. MAIN METHODS: Human IgG was
      subjected to in vitro glycation with glucose and the formation of N(epsilon)
      (carboxymethyl)lysine (CML) was evaluated by high performance liquid
      chromatography (HPLC). The immunogenicity of native and AGE-IgG was investigated
      by raising polyclonal antibodies against them in rabbits. The induced antibodies
      were purified on a Protein-A agarose affinity column. Specific binding of
      antibodies was screened by competitive inhibition assay and band shift assay.
      Cross reactions of induced antibodies with various proteins or amino acids and
      their glycated conformers were ascertained by competitive inhibition ELISA. KEY
      FINDINGS: We detected the CML formation in AGE-IgG. The AGE-IgG was found to be
      highly immunogenic due to the generation of neo-epitopes on it. Affinity purified
      antibodies exhibited high degree of specific binding with AGE-IgG in comparison
      to the native IgG. Antibodies against AGE-IgG exhibited diverse antigen binding
      characteristics and the glycated conformers of various proteins and amino acids
      were found to be effective inhibitors of antibody-immunogen interaction in cross
      reaction studies. Band shift assay reiterated the results obtained by direct
      binding and competitive inhibition assay. SIGNIFICANCE: The induced antibodies
      against AGE-IgG resembled the diverse antigen binding characteristics of
      autoantibodies found in rheumatoid arthritis (RA). IgG modified by AGEs under
      oxidative stress presents unique neo-epitopes which may be one of the factors for
      the induction of autoantibodies in RA patients.

PMID- 22634324
TI  - Assessment of the treatment effect of baicalein on a model of Parkinsonian tremor
      and elucidation of the mechanism.
AB  - AIMS: The aim of the present study is to evaluate the effects of baicalein on the
      6-hydroxydopamine (6-OHDA)-induced rat model of Parkinsonian tremor and elucidate
      the potential mechanism. MAIN METHODS: Adult male Sprague-Dawley rats were
      subjected to Parkinsonian tremor by 6-OHDA-medial forebrain bundle (MFB)
      injection. Baicalein (100, 200 and 400mg/kg) was administrated by gavage once
      daily, for 1 week. The anti-tremor effect of baicalein on a model of Parkinsonian
      tremor was examined. Dopamine (DA), glutamate (GLu) and gamma-aminobutyric acid
      (GABA) levels in basal ganglia were determined by HPLC-ECD. Cytochrome oxidase
      subunit I (COI) mRNA expression in subthalamic nucleus (STN) was assessed by real
      time RT-PCR. GABA transaminase (GABA-T) and glutamine synthetase (GS) protein
      expression in basal ganglia were tested by immunostaining. Effects of baicalein
      on [Ca(2+)]i induced by GLu were tested in primary cultured mesencephalic
      neurons. KEY FINDINGS: Baicalein significantly attenuated muscle tremor of PD
      rats. The metabolic balance between GLu and GABA was modulated by baicalein
      treatment. It was found that treatment with baicalein inhibited the STN's COI
      mRNA expression in experimental PD. In rat primary mesencephalic cultures,
      baicalein inhibited significantly GLu-induced intracellular calcium [Ca(2+)]i
      increase. SIGNIFICANCE: These results suggest that baicalein plays a
      neuromodulatory role in balancing GABA and GLu neurotransmitter in basal ganglia,
      and might be a promising candidate for the treatment of tremor-dominant type of
      idiopathic Parkinson's disease.

PMID- 22634325
TI  - A polymorphism in the upstream regulatory region of the interleukin-1alpha gene
      confers differential binding by transcription factors of the AP-1 family.
AB  - AIMS: Previous genetic studies have shown that a C/T polymorphism at position 
      889 of the IL1A promoter, specifically allele 2 (-889T), increases the risk for
      development of several inflammation-related disorders, such as periodontitis,
      osteomyelitis, toxoplasmic retinochoroiditis, contact dermatitis, as well as
      neurodegenerative conditions such as Alzheimer's disease. We sought to determine
      the differential abilities of C- and T- containing versions of the -889 sequence
      to bind nuclear proteins from microglia. MAIN METHODS: Microglial cells were
      subjected to inflammatory activation prior to the harvest of nuclear proteins.
      Electrophoretic mobility shift assays (EMSA) were performed using oligonucleotide
      probes representing 25 base pairs surrounding the IL1A -889 polymorphism.
      Antibodies reactive against transcription factors were used to identify the
      specific proteins involved in complexes with DNA. KEY FINDINGS: EMSA revealed
      multiple differences in DNA-binding profiles when microglial nuclear extracts
      were incubated with the polymorphic probes. The allele-2 probe formed specific
      complexes that were not detected with the allele-1 (-889C) probe, and vice versa.
      Formation of allele-2 nucleoprotein complexes was increased in activated
      microglia. Antibody supershift analysis indicated that multiple Jun-family
      members but not Fos-family proteins contributed to the LPS-activated allele-2
      EMSA complexes. LPS-activation of allele-2 EMSA complexes could be blocked by the
      specific c-Jun N-terminal kinase (JNK) inhibitor SP600125. SIGNIFICANCE: These
      results suggest that the -889 polymorphism creates differential interactions with
      transcription factors that could lead to differential expression rates under
      proinflammatory conditions.

PMID- 22634326
TI  - Defining the affinity and receptor sub-type selectivity of four classes of
      endothelin antagonists in clinically relevant human cardiovascular tissues.
AB  - AIMS: We have compared the endothelin receptor subtype affinity (K(D)) and
      selectivity of four structural classes of antagonists (peptide, sulphonamide
      based, carboxylic acid-based, myceric acid-based) in human cardiovascular tissues
      to determine whether these are predicted by values reported for human cloned
      receptors. Additionally, affinities (K(B)) for these antagonists, determined in
      ET-1-mediated vasoconstriction assays in human blood vessels, were used to
      identify discrepancies between K(B) and K(D) determined in the same tissues. MAIN
      METHODS: Competition binding experiments were carried out in sections of human
      left ventricle, coronary artery and homogenates of saphenous vein to determine
      K(D) values for structurally different ET(A)-selective (FR139317, BMS 182874, S97
      139, sitaxentan, ambrisentan) and mixed (PD142893, Ro462005, bosentan, L-749329,
      SB209670) antagonists. Schild-derived values of antagonist affinity were obtained
      in vascular functional studies. KEY FINDINGS: When compared with previously
      reported data in human cloned endothelin receptors, those antagonists reported to
      be ET(A)-selective exhibited even greater ET(A) selectivity in human ventricle
      (BMS 182874, sitaxentan, ambrisentan) that expressed both receptor subtypes.
      Those antagonists reported to have <100 fold selectivity in cloned receptors
      (PD142893, Ro-462005, bosentan, SB209670, L-749329) did not distinguish between
      receptor subtypes in human left ventricle. For antagonists where we determined
      affinity in vascular functional and binding assays (Ro462005, bosentan, BMS
      182874, L-749329, SB209670) there was no correlation between the degree of
      discrepancy in K(B) and K(D) and structural class. SIGNIFICANCE: For an
      antagonist to retain ET(A)-selectivity in vivo it may be necessary to identify
      those compounds that have at least 1000 fold ET(A):ET(B) selectivity in in vitro
      assays.

PMID- 22634327
TI  - Bladder outlet obstruction influences mRNA expression of cholinergic receptors on
      sensory neurons in mice.
AB  - AIMS: In patients with bladder outlet obstruction (BOO), dysregulation of bladder
      afferent neurons seems to contribute to irritative symptoms. Cholinergic
      receptors, addressed by both neuronal and non-neuronal (urothelial)
      acetylcholine, can alter neuronal excitability. Thus we investigated the
      influence of BOO on the expression of muscarinic (mAChR) and nicotinic (nAChR)
      acetylcholine receptors in the lumbosacral dorsal root ganglia (DRG) of mice.
      MAIN METHODS: BOO was induced in 13 C57/BL6 mice by partial suturing of the
      urethra. Eleven mice were sham-operated (loose/freely movable suture around the
      urethra), and eleven untreated mice served as controls. Cystometry was performed
      five weeks later in conscious mice. DRG at segmental levels L5-S2 were dissected
      and real-time quantitative PCR was performed. Expression of mAChR subtypes M1-M5
      and nAChR subunits alpha2-7, alpha9-10, beta2-4 was examined. KEY FINDINGS:
      Expression of all mAChR subtypes and nAChR subunits alpha3-7, alpha10, beta2-4
      was detected. Expression of alpha2 and alpha9 was absent. Rank order of
      expression was M2>M4>M3>M5>M1, alpha3>=alpha6>alpha7>alpha4>alpha10>alpha5 and
      beta2>beta4>beta3 in untreated animals. BOO mice presented distinct obstruction
      with development of residual urine. Sham mice showed only minimal BOO. Relative
      mRNA expression of nAChR subunits revealed significant reduction of alpha3,
      alpha5, alpha6, alpha10 and beta4 in sham-operated vs. untreated mice. In BOO vs.
      sham-operated mice, reduction of nAChR subunits alpha10 (p=0.038) and alpha5
      (p=0.053) was found. SIGNIFICANCE: BOO has a considerable impact on nAChR, but
      not on mAChR mRNA expression in sensory neurons. We hypothesize that a reduction
      in mRNA expression of nAChR subunits represents a link to altered sensitivity
      under non-obstructive conditions.

PMID- 22634328
TI  - Temperature adaptations in psychrophilic, mesophilic and thermophilic chloride
      dependent alpha-amylases.
AB  - The functional and structural adaptations to temperature have been addressed in
      homologous chloride-dependent alpha-amylases from a psychrophilic Antarctic
      bacterium, the ectothermic fruit fly, the homeothermic pig and from a
      thermophilic actinomycete. This series covers nearly all temperatures encountered
      by living organisms. We report a striking continuum in the functional properties
      of these enzymes coupled to their structural stability and related to the thermal
      regime of the source organism. In particular, thermal stability recorded by
      intrinsic fluorescence, circular dichroism and differential scanning calorimetry
      appears to be a compromise between the requirement for a stable native state and
      the proper structural dynamics to sustain the function at the
      environmental/physiological temperatures. The thermodependence of activity, the
      kinetic parameters, the activations parameters and fluorescence quenching support
      these activity-stability relationships in the investigated alpha-amylases.

PMID- 22634329
TI  - Value of Gilliatt's pneumatic tourniquet test for diagnosis of carpal tunnel
      syndrome.
AB  - OBJECTIVES: In 1953, Gilliatt and Wilson described the pneumatic-tourniquet test
      to diagnose the carpal tunnel syndrome (CTS). It was originally carried out by
      inflating a brachial cuff at suprasystolic pressure, looking for the appearance
      of dysesthesiae; several authors later proposed to perform it at infrasystolic
      pressure, arguing that it would better reflect the elevated venous pressure
      supposed to be present in CTS. The purpose of this study was to compare both
      methods. METHODS: This prospective randomized controlled study included 49
      patients and compared both methods to perform Gilliatt's test with more commonly
      used provocative tests (Tinel, Phalen, Durkan, and Weber). The following end
      points were considered: typical clinical presentation, altered neurophysiological
      tests, abnormal ultrasound findings and early resolution of symptoms after
      surgical decompression. RESULTS: For all these end-points, no significant
      difference was observed in sensibility nor specificity, whether Gilliatt's test
      was performed supra- or infra-systolic. In addition, Gilliatt's test proved to
      have less diagnostic value than Phalen and Durkan tests for sensibility.
      CONCLUSION: This study did not permit to distinguish the two versions of
      Gilliatt's test but to open a discussion about the utility of such a test to
      diagnose the CTS.

PMID- 22634330
TI  - A new Lactobacillus plantarum strain, TN8, from the gastro intestinal tract of
      poultry induces high cytokine production.
AB  - This study aimed to determine the probiotic potential of 100 strains of Lactic
      Acid Bacteria (LAB) isolated from different intestinal segments of indigenous
      poultry in Tunisia. The strains were submitted to a battery of standard tests and
      criteria commonly used for determining their probiotic properties and attributes.
      The findings revealed that 19 of the isolates exhibited antimicrobial activity
      against 4 pathogenic bacteria, and that 4 (TN1, TN8, TN7, and TN13) showed good
      resistance to pH 3 and 5% bovine bile. Three isolates, namely TN1, TN8, and TN13,
      showed sensitivity to several antibiotics and were, therefore, selected for
      further enzymatic activity assays. Two isolates, namely TN1 and TN8, showed high
      efficacy of adhesion to chicken enterocytes. The cytokines released after
      stimulation by the two isolates showed high anti-inflammatory profiles, with an
      increased rate of Interleukin-10 (IL-10) production for the TN8 strain. Showing
      the highest performance, TN8 was submitted to 16S rRNA gene sequencing, which
      revealed that the strain was of the species Lactobacillus plantarum. Overall, the
      findings indicate that the Lactobacilli from poultry intestine has a number of
      promising properties that make it candidate for application as a probiotic
      additive in poultry industry.

PMID- 22634331
TI  - Evaluation of impact of exposure of Sudan azo dyes and their metabolites on human
      intestinal bacteria.
AB  - Sudan azo dyes are banned for food usage in most countries, but they are
      illegally used to maintain or enhance the color of food products due to low cost,
      bright staining, and wide availability of the dyes. In this report, we examined
      the toxic effects of these azo dyes and their potential reduction metabolites on
      11 prevalent human intestinal bacterial strains. Among the tested bacteria, cell
      growth of 2, 3, 5, 5, and 1 strains was inhibited by Sudan I, II, III, IV, and
      Para Red, respectively. At the tested concentration of 100 MUM, Sudan I and II
      inhibited growth of Clostridium perfringens and Lactobacillus rhamnosus with
      decrease of growth rates from 14 to 47%. Sudan II also affected growth of
      Enterococcus faecalis. Growth of Bifidobacterium catenulatum, C. perfringens, E.
      faecalis, Escherichia coli, and Peptostreptococcus magnus was affected by Sudan
      III and IV with decrease in growth rates from 11 to 67%. C. perfringens was the
      only strain in which growth was affected by Para Red with 47 and 26% growth
      decreases at 6 and 10 h, respectively. 1-Amino-2-naphthol, a common metabolite of
      the dyes, was capable of inhibiting growth of most of the tested bacteria with
      inhibition rates from 8 to 46%. However, the other metabolites of the dyes had no
      effect on growth of the bacterial strains. The dyes and their metabolites had
      less effect on cell viability than on cell growth of the tested bacterial
      strains. Clostridium indolis and Clostridium ramosum were the only two strains
      with about a 10 % decrease in cell viability in the presence of Sudan azo dyes.
      The present results suggested that Sudan azo dyes and their metabolites
      potentially affect the human intestinal bacterial ecology by selectively
      inhibiting some bacterial species, which may have an adverse effect on human
      health.

PMID- 22634332
TI  - Autophagy and ageing: insights from invertebrate model organisms.
AB  - Ageing in diverse species ranging from yeast to humans is associated with the
      gradual, lifelong accumulation of molecular and cellular damage. Autophagy, a
      conserved lysosomal, self-destructive process involved in protein and organelle
      degradation, plays an essential role in both cellular and whole-animal
      homeostasis. Accumulating evidence now indicates that autophagic degradation
      declines with age and this gradual reduction of autophagy might have a causative
      role in the functional deterioration of biological systems during ageing. Indeed,
      loss of autophagy gene function significantly influences longevity. Moreover,
      genetic or pharmacological manipulations that extend lifespan in model organisms
      often activate autophagy. Interestingly, conserved signalling pathways and
      environmental factors that regulate ageing, such as the insulin/IGF-1 signalling
      pathway and oxidative stress response pathways converge on autophagy. In this
      article, we survey recent findings in invertebrates that contribute to advance
      our understanding of the molecular links between autophagy and the regulation of
      ageing. In addition, we consider related mechanisms in other organisms and
      discuss their similarities and idiosyncratic features in a comparative manner.

PMID- 22634333
TI  - Compound-specific effects of diverse neurodevelopmental toxicants on global gene
      expression in the neural embryonic stem cell test (ESTn).
AB  - Alternative assays for developmental toxicity testing are needed to reduce animal
      use in regulatory toxicology. The in vitro murine neural embryonic stem cell test
      (ESTn) was designed as an alternative for neurodevelopmental toxicity testing.
      The integration of toxicogenomic-based approaches may further increase
      predictivity as well as provide insight into underlying mechanisms of
      developmental toxicity. In the present study, we investigated concentration
      dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE),
      carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP),
      penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural
      differentiation in the ESTn. All compounds with the exception of PENG altered
      ESTn morphology (cytotoxicity and neural differentiation) in a concentration
      dependent manner. Compound induced gene expression changes and corresponding
      enriched gene ontology biological processes (GO-BP) were identified after 24h
      exposure at equipotent differentiation-inhibiting concentrations of the
      compounds. Both compound-specific and common gene expression changes were
      observed between subsets of tested compounds, in terms of significance, magnitude
      of regulation and functionality. For example, ACE, CBZ and FLU induced robust
      changes in number of significantly altered genes (>= 687 genes) as well as a
      variety of GO-BP, as compared to MEHP, PHE and PENG (<= 55 genes with no
      significant changes in GO-BP observed). Genes associated with developmentally
      related processes (embryonic morphogenesis, neuron differentiation, and Wnt
      signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In
      addition, gene expression and GO-BP enrichment showed concentration dependence,
      allowing discrimination of non-toxic versus toxic concentrations on the basis of
      transcriptomics. This information may be used to define adaptive versus toxic
      responses at the transcriptome level.

PMID- 22634334
TI  - Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa
      cells.
AB  - The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin
      (Trx), and NADPH, is ubiquitous in all cells and involved in many redox-dependent
      signaling pathways. Curcumin, a naturally occurring pigment that gives a specific
      yellow color in curry food, is consumed in normal diet up to 100mg per day. This
      molecule has also been used in traditional medicine for the treatment of a
      variety of diseases. Curcumin has numerous biological functions, and many of
      these functions are related to induction of oxidative stress. However, how
      curcumin elicits oxidative stress in cells is unclear. Our previous work has
      demonstrated the way by which curcumin interacts with recombinant TrxR1 and
      alters the antioxidant enzyme into a reactive oxygen species (ROS) generator in
      vitro. Herein we reported that curcumin can target the cytosolic/nuclear
      thioredoxin system to eventually elevate oxidative stress in HeLa cells. Curcumin
      modified TrxR1 dose-dependently and quantitatively transfers electrons from NADPH
      to oxygen with the production of ROS. Also, curcumin can drastically down
      regulate Trx1 protein level as well as its enzyme activity in HeLa cells, which
      in turn remarkably decreases intracellular free thiols, shifting the
      intracellular redox balance to a more oxidative state, and subsequently induces
      DNA oxidative damage. Furthermore, curcumin-pretreated HeLa cells are more
      sensitive to oxidative stress. Knockdown of TrxR1 sensitizes HeLa cells to
      curcumin cytotoxicity, highlighting the physiological significance of targeting
      TrxR1 by curcumin. Taken together, our data disclose a previously unrecognized
      prooxidant mechanism of curcumin in cells, and provide a deep insight in
      understanding how curcumin works in vivo.

PMID- 22634335
TI  - Successful application of a PressureWire retrogradely across an ATS prosthetic
      aortic valve to diagnose constrictive pericarditis.
AB  - Assessment of the left ventricular pressure measured across an aortic valve
      prosthesis is occasionally necessary when noninvasive imaging and Doppler
      echocardiographic data are inconclusive or differ from the clinical findings for
      specific scenarios, such as diagnosing constrictive or restrictive physiology. We
      present a case in which we safely and effectively replicate the previous
      successful application of a PressureWire in diagnosing constrictive pericarditis
      in a patient with a bileafltet mechanical aortic and mitral valves.

PMID- 22634336
TI  - Insulin resistance in the brain: an old-age or new-age problem?
AB  - Life expectancy is rising however with more people living longer there is a
      concomitant rise in the incidence of dementia. In addition to age-related
      cognitive decline there is a higher risk of going on to develop vascular dementia
      and Alzheimer's disease associated with aspects of modern lifestyle. Most
      worryingly, recent data reports accelerated cognitive decline in adolescents
      associated with poor diet (high fat and calorie intake). Thus the increase in
      dementia in 'old-age' may have as much to do with 'new-age' lifestyle as it does
      with normal ageing. It would seem wise therefore to investigate the molecular
      connections between lifestyle and cognitive decline in more detail.
      Epidemiological evidence suggests an increased risk of developing dementia
      (including Alzheimer's disease) in individuals with obesity and type 2 diabetes
      but also in those with poor insulin sensitivity without diabetes, implicating a
      mechanistic link between adiposity, insulin sensitivity and dementia. Insulin
      receptors are expressed in the brain and physiological roles for insulin in the
      CNS are starting to be delineated. Indeed disrupted neuronal insulin action may
      underlie the link between diabetes and neurodegenerative disorders. This review
      discusses the difficulties in quantifying insulin sensitivity of the brain and
      why it is vital that we develop technology for this purpose so that we can
      establish its role in this 'new-age' dementia. This has particular relevance to
      the design and interpretation of clinical trials in progress to assess potential
      benefits of insulin and insulin sensitisers on prevention of cognitive decline.

PMID- 22634337
TI  - Induction of the mitochondrial permeability transition (MPT) by micromolar iron:
      liberation of calcium is more important than NAD(P)H oxidation.
AB  - The mitochondrial permeability transition (MPT) plays an important role in cell
      death. The MPT is triggered by calcium and promoted by oxidative stress, which is
      often catalyzed by iron. We investigated the induction of the MPT by
      physiological concentrations of iron. Isolated rat liver mitochondria were
      initially stabilized with EDTA and bovine serum albumin and energized by
      succinate or malate/pyruvate. The MPT was induced by 20MUM calcium or ferrous
      chloride. We measured mitochondrial swelling, the inner membrane potential,
      NAD(P)H oxidation, iron and calcium in the recording medium. Iron effectively
      triggered the MPT; this effect differed from non-specific oxidative damage and
      required some residual EDTA in the recording medium. Evidence in the literature
      suggested two mechanisms of action for the iron: NAD(P)H oxidation due to loading
      of the mitochondrial antioxidant defense systems and uptake of iron to the
      mitochondrial matrix via a calcium uniporter. Both of these events occurred in
      our experiments but were only marginally involved in the MPT induced by iron. The
      primary mechanism observed in our experiments was the displacement of
      adventitious/endogenous calcium from the residual EDTA by iron. Although
      artificially created, this interplay between iron and calcium can well reflect
      conditions in vivo and could be considered as an important mechanism of iron
      toxicity in the cells.

PMID- 22634338
TI  - NPQ activation reduces chlorophyll triplet state formation in the moss
      Physcomitrella patens.
AB  - Plants live in variable environments in which light intensity can rapidly change,
      from limiting to excess conditions. Non-photochemical quenching (NPQ) is a
      regulatory mechanism which protects plants from oxidative stress by dissipating
      excess Chl singlet excitation. In this work, the physiological role of NPQ was
      assessed by monitoring its influence on the population of the direct source of
      light excess damage, i.e., Chl triplets ((3)Chl*). (3)Chl* formation was
      evaluated in vivo, with the moss Physcomitrella patens, by exploiting the high
      sensitivity of fluorescence-detected magnetic resonance (FDMR). A dark adapted
      sample was compared with a pre-illuminated sample in which NPQ was activated, the
      latter showing a strong reduction in (3)Chl* yield. In line with this result,
      mutants unable to activate NPQ showed only a minor effect in (3)Chl* yield upon
      pre-illumination.The decrease in (3)Chl* yield is equally experienced by all the
      Chl pools associated with PSII, suggesting that NPQ is effective in protecting
      both the core and the peripheral antenna complexes. Moreover, the FDMR results
      show that the structural reorganization in the photosynthetic apparatus, required
      by NPQ, does not lead to the formation of new (3)Chl* traps in the LHCs. This
      work demonstrates that NPQ activation leads to effective photoprotection,
      promoting a photosystem II state characterized by a reduced probability of
      (3)Chl* formation, due to a decreased singlet excited state population, while
      maintaining an efficient quenching of the (3)Chl* eventually formed by
      carotenoids.

PMID- 22634339
TI  - Ambivalent roles of early growth response 1 in inflammatory signaling following
      ribosomal insult in human enterocytes.
AB  - NF-kappaB expression and activity are strictly regulated in gut epithelia to
      prevent overstimulation of pro-inflammatory responses following exposure to
      commensal bacteria. The effects of epithelial EGR-1 on responses to bacterial NF
      kappaB-activating lipopolysaccharide (LPS) in intestinal epithelial cells under
      ribosomal stress were assessed. This was done to determine the potential of EGR-1
      as a modulator of epithelial NF-kappaB signaling. Nuclear translocation of
      phosphorylated p65 protein was observed in the cells exposed to LPS although
      chemokine expression was marginally affected. In contrast, simultaneous exposure
      to LPS and ribosomal insults prevented epithelial NF-kappaB activation while
      chemokine expression was enhanced. The effect of EGR-1, another pro-inflammatory
      signaling mediator, was monitored to determine the involvement of this factor on
      chemokine production in response to this co-treatment. Similar to the previously
      reported ribosomal stress response, EGR-1 expression was elevated by ribosomal
      insults alone and positively affected gene expression of pro-inflammatory
      chemokines in the intestinal epithelial cells. However, EGR-1 suppression led to
      super-induction of chemokines by simultaneous treatment with LPS and ribosomal
      insult, indicating that EGR-1 is a negative modulator of chemokine gene
      expression. Particularly, mucosal ribosomal insult-triggered EGR-1 mediated
      PPARgamma induction, which counteracted NF-kappaB activation by LPS. It can be
      thus concluded that EGR-1 regulates pro-inflammatory NF-kappaB activation by LPS
      via PPARgamma although EGR-1 is a positive mediator of chemokine expression
      following ribosomal insult in intestinal epithelial cells.

PMID- 22634340
TI  - Association of the IL28B genotype with insulin resistance in patients with
      chronic hepatitis C.
AB  - BACKGROUND & AIMS: Insulin resistance, fibrosis and steatosis are established
      predictors of response to peg-interferon/ribavirin therapy in chronic hepatitis C
      (CHC). Several host genetic polymorphisms (IL28B, PNPLA3) modify treatment
      outcome, the degree of steatosis or fibrosis. The aim of our study was to
      evaluate the role of these polymorphisms on insulin resistance (IR) in treatment
      naive patients with chronic hepatitis C. METHODS: Two hundred and two non
      diabetic CHC patients (GT1: 181, GT4: 21; m = 126, f = 76) undergoing liver
      biopsy in two tertiary academic centers were studied. The SNPs rs12979860 (IL28B)
      and rs738409 (PNPLA3) were investigated by RT-PCR. HOMA-IR, BMI, stage of
      fibrosis, extent of steatosis, and genetic data were analyzed. RESULTS: Insulin
      resistance (HOMA-IR >= 3.0) was associated with rs12979860 genotype, presence of
      advanced fibrosis, and higher BMI. HOMA-IR in CC and in TC/TT was 2.08 +/- 1.61
      (mean +/- SD) and 2.94 +/- 2.89 (p=0.041), respectively. HOMA-IR was higher in
      advanced than in mild fibrosis (F3-4: 3.92 +/- 3.15; F0-2: 2.38 +/- 2.38;
      p=0.004). The percentage of steatotic hepatocytes was higher in patients with
      advanced fibrosis (21.3 +/- 21.5 vs. 9.1 +/- 14.2; p<0.001), HOMA-IR >= 3.0 (17.7
      +/- 17.8 vs. 8.8 +/- 15.4%; p<0.001), and BMI > 25.0 kg/m(2) (14.7 +/- 17.0 vs.
      9.1 +/- 16.1; p<0.001). The rs738409 GG genotype was associated with advanced
      fibrosis and steatosis, but not with HOMA-IR. Multivariable logistic regression
      identified advanced fibrosis (OR: 2.820, 95% CI: 1.344-5.917; p = 0.006) and the
      IL28B genotype non-CC (OR: 3.000, 1.348-6.676; p = 0.007) as independent risk
      factors for insulin resistance. CONCLUSIONS: Insulin resistance is more common in
      carriers of the T allele of SNP rs12979860 than in CC homozygotes and may partly
      explain the poor outcome of peginterferon/ribavirin therapy in these patients.

PMID- 22634341
TI  - Erlotinib and sorafenib in an orthotopic rat model of hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: The combination of erlotinib with sorafenib is currently being
      investigated in a phase III RCT. We studied the effect of erlotinib and sorafenib
      on HCC in a preclinical model. METHODS: The Morris Hepatoma (MH) and HepG2 cells
      were treated in vitro with sorafenib (1-10 MUM) and erlotinib (1-5 MUM) and
      evaluated for tumor cell viability, apoptosis, and target regulation.
      Antiangiogenic effects were studied by measuring VEGF levels, endothelial cell
      viability, apoptosis, migration, and the aortic ring assay. In vivo, MH cells
      were implanted into the liver of syngeneic rats and treated with vehicle,
      sorafenib 5-10mg/kg, erlotinib 10mg/kg, and respective combinations. RESULTS: In
      vitro, erlotinib downregulated p-ERK but showed no significant effect on tumor
      cell viability in MH and HEPG2 cells. Despite a similar target regulation,
      sorafenib significantly reduced cell viability of HCC cells by induction of
      apoptosis, in a dose-dependent manner (11 +/- 5%; 20 +/- 10%; 51 +/- 5% for
      sorafenib 1, 5, 10 MUM). No additional effect was observed upon combination with
      erlotinib. Of note, erlotinib treatment resulted in endothelial cell migration
      and vascular sprouting of aortic rings through induction of VEGF mRNA and protein
      levels in endothelial and tumor cells, which was blocked by sorafenib. In vivo,
      erlotinib had no single agent antitumor activity, raised serum-VEGF levels, and
      lacked a synergistic effect in combination with sorafenib. CONCLUSIONS: Erlotinib
      had no antitumor effect on HCC in vitro nor in vivo, but induced VEGF, which may
      reflect a resistance mechanism to erlotinib monotherapy. No improvement of
      sorafenib efficacy was observed upon combination with erlotinib.

PMID- 22634342
TI  - Molecular MR imaging of liver fibrosis: a feasibility study using rat and mouse
      models.
AB  - BACKGROUND & AIMS: Liver biopsy, the current clinical gold standard for fibrosis
      assessment, is invasive and has sampling errors, and is not optimal for
      screening, monitoring, or clinical decision-making. Fibrosis is characterized by
      excessive accumulation of extracellular matrix proteins including type I
      collagen. We hypothesize that molecular magnetic resonance imaging (MRI) with a
      probe targeted to type I collagen could provide a direct and non-invasive method
      of fibrosis assessment. METHODS: Liver fibrosis was induced in rats with
      diethylnitrosamine and in mice with carbon tetrachloride. Animals were imaged
      prior to and immediately following i.v. administration of either collagen
      targeted probe EP-3533 or non-targeted control Gd-DTPA. Magnetic resonance (MR)
      signal washout characteristics were evaluated from T1 maps and T1-weighted
      images. Liver tissue was subjected to pathologic scoring of fibrosis and analyzed
      for gadolinium and hydroxyproline. RESULTS: EP-3533-enhanced MR showed greater
      signal intensity on delayed imaging (normalized signal enhancement mice:
      control=0.39 +/- 0.04, fibrotic=0.55 +/- 0.03, p<0.01) and slower signal washout
      in the fibrotic liver compared to controls (liver t(1/2)=51.3 +/- 3.6 vs. 42.0 +/
      2.5 min, p<0.05 and 54.5 +/- 1.9 vs. 44.1 +/- 2.9 min, p<0.01 for fibrotic vs.
      controls in rat and mouse models, respectively). Gd-DTPA-enhanced MR could not
      distinguish fibrotic from control animals. EP-3533 gadolinium concentration in
      the liver showed strong positive correlations with hydroxyproline levels (r=0.74
      (rats), r=0.77 (mice)) and with Ishak scoring (r=0.84 (rats), r=0.79 (mice)).
      CONCLUSIONS: Molecular MRI of liver fibrosis with a collagen-specific probe
      identifies fibrotic tissue in two rodent models of disease.

PMID- 22634343
TI  - Signalling mechanisms involved in apical organelle discharge during host cell
      invasion by apicomplexan parasites.
AB  - Malaria is caused by Plasmodium parasites, which belong to the phylum
      apicomplexa. The characteristic feature of apicomplexan parasites is the presence
      of apical organelles, referred to as micronemes and rhoptries, in the invasive
      stages of the parasite life cycle. Survival of these obligate intracellular
      parasites depends on successful invasion of host cells, which is mediated by
      specific molecular interactions between host receptors and parasite ligands that
      are commonly stored in these apical organelles. The timely release of these
      ligands from apical organelles to the parasite surface is crucial for receptor
      engagement and invasion. This article is a broad overview of the signalling
      mechanisms that control the regulated secretion of apical organelles during host
      cell invasion by apicomplexan parasites.

PMID- 22634344
TI  - Abnormal PfEMP1/knob display on Plasmodium falciparum-infected erythrocytes
      containing hemoglobin variants: fresh insights into malaria pathogenesis and
      protection.
AB  - Hemoglobin (Hb) variants are associated with reduced risk of life-threatening
      Plasmodium falciparum malaria syndromes, including cerebral malaria and severe
      malarial anemia. Despite decades of research, the mechanisms by which common Hb
      variants - sickle HbS, HbC, alpha-thalassemia, fetal HbF - protect African
      children against severe and fatal malaria have not been fully elucidated. In
      vitro experimental and epidemiological data have long suggested that Hb variants
      do not confer malaria protection by restricting the growth of parasites in red
      blood cells (RBCs). Recently, four Hb variants were found to impair
      cytoadherence, the binding of P. falciparum-infected RBCs (PfRBCs) to
      microvascular endothelial cells (MVECs), a centrally important event in both
      parasite survival and malaria pathogenesis in humans. Impaired cytoadherence is
      associated with abnormal display of P. falciparum erythrocyte membrane protein 1
      (PfEMP1), the parasite's major cytoadherence ligand and virulence factor, on the
      surface of host RBCs. We propose a model in which Hb variants allow parasites to
      display relatively low levels of PfEMP1, sufficient for sequestering PfRBCs in
      microvessels and avoiding their clearance from the bloodstream by the spleen. By
      preventing the display of high levels of PfEMP1, Hb variants may weaken the
      binding of PfRBCs to MVECs, compromising their ability to activate endothelium
      and initiate the downstream microvascular events that drive the pathogenesis of
      malaria.

PMID- 22634345
TI  - Adenosine signaling in normal and sickle erythrocytes and beyond.
AB  - Sickle cell disease (SCD) is a debilitating hemolytic genetic disorder with high
      morbidity and mortality affecting millions of individuals worldwide. Although SCD
      was discovered more than a century ago, no effective mechanism-based prevention
      and treatment are available due to poorly understood molecular basis of sickling,
      the fundamental pathogenic process of the disease. SCD patients constantly face
      hypoxia. One of the best-known signaling molecules to be induced under hypoxic
      conditions is adenosine. Recent studies demonstrate that hypoxia-mediated
      elevated adenosine signaling plays an important role in normal erythrocyte
      physiology. In contrast, elevated adenosine signaling contributes to sickling and
      multiple life threatening complications including tissue damage, pulmonary
      dysfunction and priapism. Here, we summarize recent research on the role of
      adenosine signaling in normal and sickle erythrocytes, progression of the disease
      and therapeutic implications. In normal erythrocytes, both genetic and
      pharmacological studies demonstrate that adenosine can enhance 2,3
      bisphosphoglycerate (2,3-BPG) production via A(2B) receptor (ADORA2B) activation,
      suggesting that elevated adenosine has an unrecognized role in normal
      erythrocytes to promote O(2) release and prevent acute ischemic tissue injury.
      However, in sickle erythrocytes, the beneficial role of excessive adenosine
      mediated 2,3-BPG induction becomes detrimental by promoting deoxygenation,
      polymerization of sickle hemoglobin and subsequent sickling. Additionally,
      adenosine signaling via the A(2A) receptor (ADORA2A) on invariant natural killer
      T (iNKT) cells inhibits iNKT cell activation and attenuates pulmonary dysfunction
      in SCD mice. Finally, elevated adenosine coupled with ADORA2BR activation is
      responsible for priapism, a dangerous complication seen in SCD. Overall, the
      research reviewed here reveals a differential role of elevated adenosine in
      normal erythrocytes, sickle erythrocytes, iNK cells and progression of disease.
      Thus, adenosine signaling represents a potentially important therapeutic target
      for the treatment and prevention of disease.

PMID- 22634347
TI  - Extracellular NAD(+): a danger signal hindering regulatory T cells.
AB  - Endogenous danger signals released during cell damage contribute to alert the
      immune system. Typically, their release results in the activation and maturation
      of innate immune cells, and the production of pro-inflammatory cytokines. In
      addition, extracellular NAD(+) stimulates immune responses by hindering
      regulatory T cells (Tregs), and could, therefore, represent the prototype of a
      new category of danger signals.

PMID- 22634346
TI  - Role of extracellular nucleotides in the immune response against intracellular
      bacteria and protozoan parasites.
AB  - Extracellular nucleotides are danger signals involved in recognition and control
      of intracellular pathogens. They are an important component of the innate immune
      response against intracellular pathogens, inducing the recruitment of
      inflammatory cells, stimulating secretion of cytokines, and producing
      inflammatory mediators such as reactive oxygen species (ROS) and nitric oxide
      (NO). In the case of extracellular ATP, some of the immune responses are mediated
      through activation of the NLRP3 inflammasome and secretion of the cytokine,
      interleukin-1beta (IL-1beta), through a mechanism dependent on ligation of the
      P2X7 receptor. Here we review the role of extracellular nucleotides as sensors of
      intracellular bacteria and protozoan parasites, and discuss how these pathogens
      manipulate purinergic signaling to diminish the immune response against
      infection.

PMID- 22634348
TI  - Multiple small bowel intussusceptions in an adult male.

PMID- 22634350
TI  - An elderly patient on warfarin with rectal bleeding.

PMID- 22634349
TI  - Complete biliary obstruction without jaundice.

PMID- 22634351
TI  - Abdominal pain with vomiting for 1 day after subtotal gastrectomy more than 20
      years ago.

PMID- 22634353
TI  - Combined prophylaxis is still better than vaccine only in children of HBV
      infected mothers with negative HBeAg.

PMID- 22634354
TI  - Adalimumab induces and maintains clinical remission in patients with moderate-to
      severe ulcerative colitis.

PMID- 22634355
TI  - Well that changes everything! The genesis of memory bias for threat with
      implications for delayed onset in anxiety disorders.
AB  - BACKGROUND AND OBJECTIVES: A number of aetiological pathways have been proposed
      in the development of anxiety disorders, including those associated with
      stressful triggering situations. Life events can provide new meaning to past
      situations, potentially leading to the delayed onset of a disorder. Whether or
      not a disorder will emerge is theoretically related to one's appraisal and memory
      of prior events, and memory biases are proposed to exist for threat-related
      information in association with anxiety. Given that new events may change the
      meaning of past experiences, threatening information may change one's memory for
      once-neutral events. METHODS: The current study aimed to examine the effect of
      threatening information on memory for previously encoded (neutral) stimuli.
      Undergraduate participants (n = 81) interacted with 30 neutral objects (displayed
      in two boxes) and completed a recall memory test for these objects. They were
      then randomly assigned to receive either new threatening or new neutral
      information about half (one box) of the already-learned objects; a second recall
      test was then administered. RESULTS: Individuals given threatening information
      showed a greater proportion of memory for items that were manipulated to total
      items recalled than did individuals given new non-threatening information.
      LIMITATIONS: A nonclinical sample reported relatively low ratings of disgust and
      anxiety. Additionally, the time between the two memory tests was brief, likely
      differing from the actual occurrence of delayed onset disorders. CONCLUSIONS:
      Results showed the genesis of a memory bias for threat in the presumed absence of
      an attentional bias, and are discussed in terms of the delayed onset of anxiety
      disorders.

PMID- 22634356
TI  - Sipunculan larvae and "cosmopolitan" species.
AB  - Sipuncula is a relatively small taxon with roughly 150 recognized species. Many
      species are geographically widespread or "cosmopolitan." The pelagosphera larvae
      of some species are estimated to spend several months in the plankton. However,
      recent molecular evidence suggests that many of the "cosmopolitan" species
      actually represent species-complexes, some not even monophyletic. Herein, we
      present data on three sipunculan species with different developmental modes that
      occur both in the Sea of Japan and in the Northeast Pacific. The development of
      the three species-Phascolosoma agassizii, Thysanocardia nigra, and Themiste
      pyroides-is exceptionally well studied in both regions of the Pacific.
      Significant differences have been observed between the two regions with respect
      to egg size, developmental mode, and developmental timing. In general, eggs are
      larger and development slower in the Northeast Pacific when compared with the Sea
      of Japan. These differences have been explained as a result of phenotypic
      plasticity exhibited under different environmental conditions, in particular
      temperature, but we show that the populations of all three species are also
      remarkably distinct genetically and that gene flow between the two regions is
      extremely unlikely. In Thysanocardia nigra, we even found two very distinct
      genetic lineages within the same location in the Northeast Pacific. The amount of
      genetic divergence between populations from the Sea of Japan and those from the
      Northeast Pacific is not correlated with developmental mode. Themiste pyroides,
      the species with the most abbreviated development, actually has the least degree
      of genetic divergence between the regions. Analyses of molecular variance show
      that the majority of the observed variation in all three species is between the
      regions. We conclude that all three "cosmopolitan" species actually represent
      complexes of cryptic or pseudo-cryptic species. These examples demonstrate that a
      solid taxonomic framework based on molecular and morphological evidence is a
      prerequisite for evaluating relationships between dispersal capabilities,
      species' ranges, and the connectivity of populations.

PMID- 22634357
TI  - Natural selection, larval dispersal, and the geography of phenotype in the sea.
AB  - Populations evolve generalist, specialist, and plastic strategies in response to
      environmental heterogeneity. Describing such within-species variation in
      phenotype and how it arises is central to understanding a variety of ecological
      and evolutionary topics. The literature on phenotypic differences among
      populations is highly biased; for every one article published on a marine
      species, at least 10 articles are published on a terrestrial species and eight
      focus on terrestrial plants. Here, I outline what we know from the marine
      literature about geographic variation in phenotype in the sea, with a principal
      focus on local adaptation. The theory of environmental "grain" predicts that the
      most likely evolutionary response (e.g., local adaptation, phenotypic plasticity,
      generalism, and balanced polymorphism) depends on the spatial scale of
      environmental variation relative to the distance that an organism disperses.
      Consistent with these predictions, phenotypic plasticity is stronger among
      invertebrates with geographically broad dispersal versus restricted dispersal
      (i.e., planktonic-dispersers versus direct-developers). However, contrary to
      predictions, the relative frequency, and spatial scale of local adaptation is not
      consistently greater among direct-developers relative to planktonic disperers.
      This indicates that the likelihood of local adaptation depends on other
      organismal or environmental traits. Two of the most vexing issues that remain
      include (1) predicting the extent to which barriers to dispersal are a cause
      versus consequence of phenotypic differentiation and (2) delineating the relative
      importance of evolutionary forces that favor or impede local adaptation.
      Understanding the mechanistic basis of the geography of phenotypic differences,
      or phenogeography, has gained recent momentum because of a need to predict
      impacts of global climatic change, anthropogenic disturbances, and dispersal of
      organisms to non-native habitats.

PMID- 22634358
TI  - Independent innovation in the evolution of paddle-shaped tails in viviparous sea
      snakes (Elapidae: Hydrophiinae).
AB  - The viviparous sea snakes (Hydrophiinae) comprise ~90% of living marine reptiles
      and display many physical and behavioral adaptations for breathing, diving, and
      achieving osmotic balance in marine habitats. Among the most important
      innovations found in marine snakes are their paddle-shaped (dorsoventrally
      expanded) tails, which provide propulsive thrust in the dense aquatic medium.
      Here, we reconstruct the evolution of caudal paddles in viviparous sea snakes
      using a dated molecular phylogeny for all major lineages and computed tomography
      of internal osteological structures. Bayesian ancestral state reconstructions
      show that extremely large caudal paddles supported by elongated vertebral
      processes are unlikely to have been present in the most recent common ancestor of
      extant sea snakes. Instead, these characters appear to have been acquired
      independently in two highly marine lineages of relatively recent origin. Both the
      Aipysurus and Hydrophis lineages have elongated neural spines that support the
      dorsal edge of their large paddles. However, whereas in the Aipysurus lineage the
      ventral edge of the paddle is supported by elongated haemapophyses, this support
      is provided by elongated and ventrally directed pleurapophyses in the Hydrophis
      lineage. Three semi-marine lineages (Hydrelaps, Ephalophis, and Parahydrophis)
      form the sister group to the Hydrophis clade and have small paddles with poorly
      developed dorsal and ventral supports, consistent with their amphibious
      lifestyle. Overall, our results suggest that not only are the viviparous
      hydrophiines the only lineage of marine snakes to have acquired extremely large,
      skeletally supported caudal paddles but also that this innovation has occurred
      twice in the group in the past ~2-6 million years.

PMID- 22634359
TI  - Thrombolysis during resuscitation: should we focus on sudden cardiac arrest after
      myocardial infarction?

PMID- 22634360
TI  - Metabotropic glutamate receptor 4 in the basal ganglia of parkinsonian monkeys:
      ultrastructural localization and electrophysiological effects of activation in
      the striatopallidal complex.
AB  - Group III metabotropic glutamate receptors (mGluR4,7,8) are widely distributed in
      the basal ganglia. Injection of group III mGluR agonists into the striatopallidal
      complex alleviates parkinsonian symptoms in 6-hydroxydopamine-treated rats. In
      vitro rodent studies have suggested that this may be partly due to modulation of
      synaptic transmission at striatopallidal and corticostriatal synapses through
      mGluR4 activation. However, the in vivo electrophysiological effects of group III
      mGluRs activation upon basal ganglia neurons activity in nonhuman primates remain
      unknown. Thus, in order to examine the anatomical substrates and physiological
      effects of group III mGluRs activation upon striatal and pallidal neurons in
      monkeys, we used electron microscopy immunohistochemistry to localize mGluR4,
      combined with local administration of the group III mGluR agonist L-AP4, or the
      mGluR4 positive allosteric modulator VU0155041, to assess the effects of group
      III mGluR activation on the firing rate and pattern of striatal and pallidal
      neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated
      parkinsonian monkeys. At the ultrastructural level, striatal mGluR4
      immunoreactivity was localized in pre- (60%) and post-synaptic (30%) elements,
      while in the GPe, mGluR4 was mainly expressed pre-synaptically (90%). In the
      putamen, terminals expressing mGluR4 were evenly split between putative
      excitatory and inhibitory terminals, while in the GPe, most labeled terminals
      displayed the ultrastructural features of striatal-like inhibitory terminals,
      though putative excitatory boutons were also labeled. No significant difference
      was found between normal and parkinsonian monkeys. Extracellular recordings in
      awake MPTP-treated monkeys revealed that local microinjections of small volumes
      of L-AP4 resulted in increased firing rates in one half of striatal cells and one
      third of pallidal cells, while a significant number of neurons in both structures
      showed either opposite effects, or did not display any significant rate changes
      following L-AP4 application. VU0155041 administration had little effect on firing
      rates. Both compounds also had subtle effects on bursting and oscillatory
      properties, acting to increase the irregularity of firing. The occurrence of
      pauses in firing was reduced in the majority (80%) of GPe neurons after L-AP4
      injection. Our findings indicate that glutamate can mediate multifarious
      physiological effects upon striatal and pallidal neurons through activation of
      pre-synaptic group III mGluRs at inhibitory and excitatory synapses in
      parkinsonian monkeys. This article is part of a Special Issue entitled
      'Metabotropic Glutamate Receptors'.

PMID- 22634361
TI  - Anxiolytic- but not antidepressant-like activity of Lu AF21934, a novel,
      selective positive allosteric modulator of the mGlu4 receptor.
AB  - Previous studies demonstrated that the Group III mGlu receptor-selective
      orthosteric agonist, LSP1-2111 produced anxiolytic- but not antidepressant-like
      effects upon peripheral administration. Herein, we report the pharmacological
      actions of Lu AF21934, a novel, selective, and brain-penetrant positive
      allosteric modulator (PAM) of the mGlu(4) receptor in the stress-induced
      hyperthermia (SIH), four-plate, marble-burying and Vogel's conflict tests. In all
      models, except Vogel's conflict test, a dose-dependent anxiolytic-like effect was
      seen. The anti-hyperthermic effect of Lu AF21934 (5 mg/kg) in the SIH test was
      inhibited by the benzodiazepine receptor antagonist flumazenil (10 mg/kg) and was
      not serotonin-dependent, as it persisted in serotonin-deficient mice and upon
      blockade of either 5-HT(1A) receptors by WAY100635, or 5-HT(2A/2C) receptors by
      ritanserin. These results suggest that the GABAergic system, but not the
      serotonergic system, is involved in the mechanism of the anxiolytic-like
      phenotype of Lu AF21934 in rodents. Lu AF21934 did not produce antidepressant
      like effects in the tail suspension test (TST) in mice; however, it decreased the
      basal locomotor activity of mice that were not habituated to activity cages. This
      article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.

PMID- 22634362
TI  - Behavioral effects of taurine pretreatment in zebrafish acutely exposed to
      ethanol.
AB  - Taurine (TAU) is an amino sulfonic acid that plays protective roles against
      neurochemical impairments induced by ethanol (EtOH). Mounting evidence shows the
      applicability of zebrafish for evaluating locomotor parameters and anxiety-like
      behavioral phenotypes after EtOH exposure in a large scale manner. In this study,
      we assess the effects of TAU pretreatment on the behavior of zebrafish in the
      open tank after acute 1% EtOH (v/v) exposure (20 and 60 min of duration) and on
      brain alcohol contents. The exposure for 20 min exerted significant anxiolytic
      effects, which were prevented by 42, 150, and 400 mg/L TAU. Conversely, the 60
      min condition induced depressant/sedative effects, in which the changes on
      vertical activity were associated to modifications on the exploratory profile.
      Although all TAU concentrations kept locomotor parameters at basal levels, 150
      mg/L TAU, did not prevent the impairment on vertical activity of EtOH[60].
      Despite the higher brain EtOH content detected in the 60-min exposure, 42, 150,
      and 400 mg/L TAU attenuated the increase of alcohol content in EtOH[60] group. In
      conclusion, our data suggest that both protocols of acute EtOH exposure induce
      significant changes in the spatio-temporal behavior of zebrafish and that TAU may
      exert a preventive role by antagonizing the effects induced by EtOH possibly due
      to its neuromodulatory role and also by decreasing brain EtOH levels. The
      hormetic dose-response of TAU on vertical exploration suggests a complex
      interaction between TAU and EtOH in the central nervous system.

PMID- 22634363
TI  - Group I metabotropic glutamate autoreceptors induce abnormal glutamate exocytosis
      in a mouse model of amyotrophic lateral sclerosis.
AB  - Glutamate-mediated excitotoxicity plays a major role in ALS and reduced
      astrocytic glutamate transport was suggested as a cause. Based on previous work
      we have proposed that abnormal release may represent another source of excessive
      glutamate. In this line, here we studied the modulation of glutamate release in
      ALS by Group I metabotropic glutamate (mGlu) receptors, that comprise mGlu1 and
      mGlu5 members. Synaptosomes from the lumbar spinal cord of SOD1/G93A mice, a
      widely used murine model for human ALS, and controls were used in release,
      confocal or electron microscopy and Western blot experiments. Concentrations of
      the mGlu1/5 receptor agonist 3,5-DHPG >0.3 MUM stimulated the release of [(3)H]d-
      aspartate, used to label the releasing pools of glutamate, both in control and
      SOD1/G93A mice. At variance, <=0.3 MUM 3,5-DHPG increased [(3)H]d-aspartate
      release in SOD1/G93A mice only. Experiments with selective antagonists indicated
      the involvement of both mGlu1 and mGlu5 receptors, mGlu5 being preferentially
      involved in the high potency effects of 3,5-DHPG. High 3,5-DHPG concentrations
      increased IP3 formation in both mouse strains, whereas low 3,5-DHPG did it in
      SOD1/G93A mice only. Release experiments confirmed that 3,5-DHPG elicited [(3)H]d
      aspartate exocytosis involving intra-terminal Ca(2+) release through IP3
      sensitive channels. Confocal microscopy indicated the co-existence of both
      receptors presynaptically in the same glutamatergic nerve terminal in SOD1/G93A
      mice. To conclude, activation of mGlu1/5 receptors produced abnormal glutamate
      release in SOD1/G93A mice, suggesting that these receptors are implicated in ALS
      and that selective antagonists may be predicted for new therapeutic approaches.
      This article is part of a Special Issue entitled 'Metabotropic Glutamate
      Receptors'.

PMID- 22634364
TI  - Effects of environmental enrichment on the incubation of cocaine craving.
AB  - Recent studies have demonstrated that exposure to environmental enrichment (EE)
      during withdrawal periods reduces the risks of relapse to drug-seeking behavior.
      In this study, we investigated whether EE could prevent the development of time
      dependent increases in cocaine-seeking behavior (incubation of craving). In
      addition, we investigated whether EE could eliminate already developed incubation
      and whether the effects of EE would last when enrichment is discontinued. For
      this, we allowed rats to self-administer cocaine for 10 daily 6 h sessions and
      measured cocaine-seeking 1, 30 and 60 days after the last self-administration
      session. In between these tests, rats were kept in forced abstinence and housed
      either in EE or standard environments (SE). Between day 30 and 60 of withdrawal,
      half of the rats in each group were maintained in their original environmental
      condition and the other half was switched to the other environmental condition.
      We found that exposure to EE prevents development of incubation of cocaine
      craving and eliminates already developed incubation. In addition, contrary to our
      expectations, when EE was discontinued, its positive effects on incubation of
      craving disappeared. These results indicate that EE can reduce cocaine seeking
      but only temporarily and questions the hypothesis that EE can permanently
      eliminate the neural consequences of exposure to drugs of abuse. Therefore,
      stimulating environments could have positive effects on the treatment of cocaine
      addiction only if they are maintained for long periods of abstinence that
      encompass the time-frame during which addicts are most vulnerable to relapse.

PMID- 22634365
TI  - Androsterone-induced molecular and physiological changes in maize seedlings in
      response to chilling stress.
AB  - The aim of study was to elucidate the influence of foliar sprays of androsterone
      in alleviating detrimental effects of chilling stress in maize seedlings. Eleven
      days-old maize seedlings were treated with 10(-9) mol L(-1) androsterone and then
      transferred to a chamber with temperature of 10/7  degrees C (day/night) for 3
      days. The stress injury was measured in terms of increase in electrolyte leakage,
      superoxide production and hydrogen peroxide level, and decrease in chlorophyll
      content. Androsterone application mitigated significantly the chilling-induced
      stress injury. Under chilling stress, the oxidative damage which was measured as
      malondialdehyde content was lesser in androsterone-applied seedlings that were
      associated with greater activities of superoxide dismutase (SOD), catalase (CAT),
      guaiacol peroxidase (POX), ascorbate peroxidase (APX) and glutathione reductase
      (GR). Moreover, SOD, POX and APX isozymes exhibited a strong correlation with
      changes in their activities. Androsterone application enhanced the level of
      antioxidant compounds like ascorbic acid, glutathione, proline and carotenoid as
      well as activities of antioxidant enzymes. Similarly, while androsterone
      treatment increased total antioxidant status, it reduced total oxidant status
      relative to chilling-stressed seedlings alone. Soluble protein profile was
      significantly changed by only chilling stress and chilling stress plus
      androsterone treatment, as well. According to these findings, it is possible to
      say that androsterone could be used to alleviate the damaging effects of chilling
      stress by improving antioxidative system in maize seedlings. This is the first
      study elucidating the effects of androsterone on resistance to chilling stress of
      plants.

PMID- 22634366
TI  - Alteration of secondary metabolites' profiles in potato leaves in response to
      weakly and highly aggressive isolates of Phytophthora infestans.
AB  - Phytophthora infestans is the cause of late blight, a devastating disease in
      potato and tomato. Many of the mechanisms underlying P. infestans pathogenesis
      and defense responses in potato are still unclear. We investigated the effects of
      P. infestans on the changes in the accumulation of secondary metabolites in
      potato cultivars using whole plants. Four preformed flavonoids and one terpenoid
      compound produced in potato tissues were differentially affected by the P.
      infestans inoculation. In Russet Burbank, the accumulation of catechin and rutin
      was suppressed by both P. infestans isolates US-11 and US-8, while the flavanone
      P3 was associated with susceptibility to this pathogen. On the other hand,
      catechin, flavonol-glycoside P2, and an unidentified terpenoid (T1), may be
      involved in the defense of cultivar Defender to both tested P. infestans
      isolates, providing new evidence that different preformed flavonoids and
      terpenoids in potato may play important roles in its defense or susceptibility to
      P. infestans. These results add to the pool of data showing the involvement of
      other phenolics and terpenes in potato resistance to microbial pathogens.

PMID- 22634367
TI  - Sleep disturbance, inflammation and depression risk in cancer survivors.
AB  - Over two-thirds of the 11.4 million cancer survivors in the United States can
      expect long-term survival, with many others living with cancer as a chronic
      disease controlled by ongoing therapy. However, behavioral co-morbidities often
      arise during treatment and persist long-term to complicate survival and reduce
      quality of life. In this review, the inter-relationships between cancer,
      depression, and sleep disturbance are described, with a focus on the role of
      sleep disturbance as a risk factor for depression. Increasing evidence also links
      alterations in inflammatory biology dynamics to these long-term effects of cancer
      diagnosis and treatment, and the hypothesis that sleep disturbance drives
      inflammation, which together contribute to depression, is discussed. Better
      understanding of the associations between inflammation and behavioral co
      morbidities has the potential to refine prediction of risk and development of
      strategies for the prevention and treatment of sleep disturbance and depression
      in cancer survivors.

PMID- 22634369
TI  - Age-related changes in mitochondrial membrane composition of rainbow trout
      (Oncorhynchus mykiss) heart and brain.
AB  - Membrane composition, particularly of mitochondria, could be a critical factor by
      determining the propagation of reactions involved in mitochondrial function
      during periods of high oxidative stress such as rapid growth and aging.
      Considering that phospholipids not only contribute to the structural and physical
      properties of biological membranes, but also participate actively in cell
      signaling and apoptosis, changes affecting either class or fatty acid
      compositions could affect phospholipid properties and, thus, alter mitochondrial
      function and cell viability. In the present study, heart and brain mitochondrial
      membrane phospholipid compositions were analyzed in rainbow trout during the four
      first years of life, a period characterized by rapid growth and a sustained high
      metabolic rate. Specifically, farmed fish of three ages (1-, 2- and 4-years) were
      studied, and phospholipid class compositions of heart and brain mitochondria, and
      fatty acid compositions of individual phospholipid classes were determined.
      Rainbow trout heart and brain mitochondria showed different phospholipid
      compositions (class and fatty acid), likely related to tissue-specific functions.
      Furthermore, changes in phospholipid class and fatty acid compositions with age
      were also tissue-dependent. Heart mitochondria had lower proportions of
      cardiolipin (CL), phosphatidylserine (PS) and phosphatidylinositol, and higher
      levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) with age.
      Heart mitochondrial membranes became more unsaturated with age, with a
      significative increase of peroxidation index in CL, PS and sphingomyelin (SM).
      Therefore, heart mitochondria became more susceptible to oxidative damage with
      age. In contrast, brain mitochondrial PC and PS content decreased in 4-year-old
      animals while there was an increase in the proportion of SM. The three main
      phospholipid classes in brain (PC, PE and PS) showed decreased n-3
      polyunsaturated fatty acids, docosahexaenoic acid and peroxidation index, which
      indicate a different response of brain mitochondrial lipids to rapid growth and
      maturation.

PMID- 22634368
TI  - Carotid chemoreceptor development in mice.
AB  - Mice are the most suitable species for understanding genetic aspects of postnatal
      developments of the carotid body due to the availability of many inbred strains
      and knockout mice. Our study has shown that the carotid body grows differentially
      in different mouse strains, indicating the involvement of genes. However, the
      small size hampers investigating functional development of the carotid body.
      Hypoxic and/or hyperoxic ventilatory responses have been investigated in newborn
      mice, but these responses are indirect assessment of the carotid body function.
      Therefore, we need to develop techniques of measuring carotid chemoreceptor
      neural activity from young mice. Many studies have taken advantage of the
      knockout mice to understand chemoreceptor function of the carotid body, but they
      are not always suitable for addressing postnatal development of the carotid body
      due to lethality during perinatal periods. Various inbred strains with well
      designed experiments will provide useful information regarding genetic mechanisms
      of the postnatal carotid chemoreceptor development. Also, targeted gene deletion
      is a critical approach.

PMID- 22634370
TI  - The heart-protective mechanism of nitronyl nitroxide radicals on murine viral
      myocarditis induced by CVB3.
AB  - Our previous researches showed that nitronyl nitroxyl derivatives, NNP and NNVP
      were good anti-oxidants and provided radioprotective effects in C6 cells. The
      objective of the present study is to investigate the possible antiviral effects
      and underlying pharmacological of the two nitronyl nitroxide radicals against
      CVB3 in vitro and in vivo. The results showed that NNP and NNVP were some of the
      most potent compounds in terms of their antiviral effects by protecting
      myocardial cells against oxidative damage of free radicals. Treatment with NNP or
      NNVP could decrease the intracellular ROS level in vitro. They could lead to a
      significant decrease in activities of biochemical markers AST, CK and LDH in
      infected murine serum and could increase SOD and CAT activities and decreased MDA
      activities compared with infected control in vivo. NNP and NNVP could reduce NO
      production in infected mice by reacting with NO to produce the imino nitroxides
      which was confirmed by ESR spectrometry. In addition, NNP and NNVP could both
      decrease the mRNA expression of proinflammatory cytokines, TNF-alpha, IL-2 and IL
      6. In conclusion, nitronyl nitroxide radicals NNP and NNVP were shown to have
      antiviral activities against CVB3 and they may represent potential therapeutic
      agents for viral myocarditis.

PMID- 22634371
TI  - Mechanisms of DNA methylation and demethylation in mammals.
AB  - Cytosine methylation is an epigenetically propagated DNA modification that can
      modify how the DNA molecule is recognized and expressed. DNA methylation
      undergoes extensive reprogramming during mammalian embryogenesis and is directly
      linked to the regulation of pluripotency and cellular identity. Studying its
      regulation is also important for a better understanding of the many diseases that
      show epigenetic deregulations, in particular, cancer. In the recent years, a lot
      of progress has been made to characterize the profiles of DNA methylation at the
      genome level, which revealed that patterns of DNA methylation are highly dynamic
      between cell types. Here, we discuss the importance of DNA methylation for genome
      regulation and the mechanisms that remodel the DNA methylome during mammalian
      development, in particular the involvement of the rediscovered modified base 5
      hydroxymethylcytosine.

PMID- 22634372
TI  - Brain transcriptomic profiling in idiopathic and LRRK2-associated Parkinson's
      disease.
AB  - LRRK2 mutations are the most common genetic cause of Parkinson's disease (PD). We
      performed a whole-genome RNA profiling of locus coeruleus post-mortem tissue, a
      histopathologically affected brain tissue in PD, from idiopathic PD (IPD) and
      LRRK2-associated PD patients. The differentially expressed genes found in IPD and
      LRRK2-associated PD are involved in the gene ontology terms of synaptic
      transmission and neuron projection. In addition, differentially expressed genes
      in the IPD group are associated with immune system related pathways.
      Specifically, the study performed highlights the presence of differential
      expression of genes located in the chromosome 6p21.3 belonging to the class II
      HLA. Our findings support the hypothesis of a potential role of neuroinflammation
      and the involvement of the HLA genetic area in IPD pathogenesis. Future studies
      are necessary to shed light on the relation of immune system related pathways in
      the etiopathogenesis of PD.

PMID- 22634373
TI  - Stimulus complexity modulates contrast response functions in the human middle
      temporal area (hMT+).
AB  - The brain systems that support motion perception are some of the most studied in
      the primate visual system, with apparent specialization in the middle temporal
      area (hMT+ in humans, MT or V5 in monkeys). Even with this specialization, it is
      safe to assume that the hMT+ interacts with other brain systems as visual tasks
      demand. Here we have measured those interactions using a specialized case of
      structure-from-motion, point-light biological motion. We have measured the BOLD
      contrast response functions in hMT+ for translating and biological motion. Even
      after controlling for task and attention, we find the BOLD response for
      translating motion to be largely insensitive to contrast, but the BOLD response
      for biological motion to be strongly contrast dependent. To track the brain
      systems involved in these interactions, we probed for brain areas outside of the
      hMT+ with the same contrast dependent neural response. This analysis revealed
      brain systems known to support form perception (including ventral temporal cortex
      and the superior temporal sulcus). We conclude that the contrast dependent
      response in hMT+ likely reflects stimulus complexity, and may be evidence for
      interactions with shape-based brain systems.

PMID- 22634374
TI  - Cortical processing of change in sound location: smooth motion versus
      discontinuous displacement.
AB  - The detection of a change in space is an essential prerequisite of adequate
      responding to dynamic aspects of our auditory environment, be it induced by
      smooth motion or abrupt and discontinuous displacements of ongoing sound sources.
      Here, we investigated the auditory processing of different types of spatial
      change using electroencephalography. While fixating straight ahead, participants
      listened to a free-field sound stimulus that, after an initial stationary phase
      in a central position, either (1) started to move horizontally (motion stimulus),
      or (2) changed repetitively its spatial position in random order within left or
      right hemispaces (scatter stimulus), or (3) shifted abruptly toward a lateral
      position (displacement stimulus). Irrespective of stimulus type, the onset of
      spatial change elicited a characteristic sequence of auditory evoked potentials
      that was similar to the so-called motion-onset response described in previous
      studies. Differences in response amplitudes and latencies to the different
      stimulus types were only gradual, with scatter and displacement producing
      generally stronger responses than motion. Also, inter-hemispheric asymmetry
      patterns in the responses to scatter differed somewhat from those obtained with
      the other types of changes in position. Rather than any substantial stimulus
      specific differences, the findings suggest the existence of an auditory "spatial
      change response," that is, a common electrophysiological correlate of auditory
      processing of any spatial change in the environment that does not necessarily
      need to involve motion as such.

PMID- 22634376
TI  - Dopaminergic differentiation of neural progenitors derived from placental
      mesenchymal stem cells in the brains of Parkinson's disease model rats and
      alleviation of asymmetric rotational behavior.
AB  - Parkinson's disease (PD) is caused by the progressive loss of dopaminergic
      neurons in the mesencephalic substantia nigra and is accompanied by behavioral
      abnormalities. Pharmacological administration of L-dihydroxyphenylalanine (l
      dopa) improves the abnormalities in the early phase of the illness, but numerous
      adverse effects hinder long-term administration. Transplantation of fetal
      mesencephalic tissues has been suggested as an alternative to l-dopa treatment;
      however, the use of human fetal tissues is controversial. Mesenchymal stem cells
      (MSCs) are capable of self-renewal and differentiation and are thus a promising
      substitute for fetal tissue for the replacement of diseased tissues or organs.
      Previously, this group isolated 17 independent MSCs from the first trimester
      human placenta (termed first trimester placental MSCs, or fPMSCs) and reported
      their successful in vitro differentiation into fPMSC-derived neural progenitors
      (fPMSC-NPs) (Park et al., Placenta 2011; 32:269-276). In the current study, the
      in vitro-generated fPMSC-NPs were transplanted into the striatum of a rat model
      of PD to evaluate whether they could undergo terminal differentiation and mediate
      behavioral recovery. As early as 2 weeks after transplantation, a minor but
      significant amelioration of rotational asymmetry was observed, and near-normal
      motor function was achieved at 24weeks. Immunohistochemical and positron emission
      tomography (PET) analyses provided experimental evidence for the dopaminergic
      differentiation of the transplanted progenitors. These results show that in vitro
      generated fPMSC-NPs are capable of terminal differentiation in vivo and can
      attenuate motor defects associated with PD. Hence, the placenta is an auspicious
      source of stem cells for the therapeutic treatment of neurological disorders.

PMID- 22634375
TI  - Development of white matter pathways in typically developing preadolescent
      children.
AB  - The first phase of major neuronal rearrangements in the brain takes place during
      the prenatal period. While the brain continues maturation throughout childhood, a
      critical second phase of synaptic overproduction and elimination takes place
      during the preadolescent period. Despite the importance of this developmental
      phase, few studies have evaluated neural changes taking place during this period.
      In this study, MRI diffusion tensor imaging data from a normative sample of 126
      preadolescent children (59 girls and 67 boys) between the ages of 6 and 10 years
      were analyzed in order to characterize age-relationships in the white matter
      microstructure. Tract Based Spatial Statistics (TBSS) method was used for whole
      brain analysis of white matter tracts without a priori assumption about the
      location of age associated differences. Our results demonstrate significant age
      associated differences in most of the major fiber tracts bilaterally and along
      the whole body of the tracts. In contrast, developmental differences in the
      cingulum at the level of the parahippocampal region were only observed in the
      right hemisphere. We suggest that these age-relationships with a widespread
      distribution seen during the preadolescent years maybe relevant for the
      implementation of cognitive and social behaviors needed for a normal development
      into adulthood.

PMID- 22634377
TI  - Post-translational modifications of TRF1 and TRF2 and their roles in telomere
      maintenance.
AB  - Telomeres, heterochromatic structures, found at the ends of linear eukaryotic
      chromosomes, function to protect natural chromosome ends from nucleolytic attack.
      Human telomeric DNA is bound by a telomere-specific six-subunit protein complex,
      termed shelterin/telosome. The shelterin subunits TRF1 and TRF2 bind in a
      sequence-specific manner to double-stranded telomeric DNA, providing a vital
      platform for recruitment of additional shelterin proteins as well as non
      shelterin factors crucial for the maintenance of telomere length and structure.
      Both TRF1 and TRF2 are engaged in multiple roles at telomeres including telomere
      protection, telomere replication, sister telomere resolution and telomere length
      maintenance. Regulation of TRF1 and TRF2 in these various processes is controlled
      by post-translational modifications, at times in a cell-cycle-dependent manner,
      affecting key functions such as DNA binding, dimerization, localization,
      degradation and interactions with other proteins. Here we review the post
      translational modifications of TRF1 and TRF2 and discuss the mechanisms by which
      these modifications contribute to the function of these two proteins.

PMID- 22634378
TI  - Antibiotic resistance: how serious is the problem, and what can be done?

PMID- 22634379
TI  - Cardiac troponin T measured by a high-sensitivity assay predicts recurrent
      cardiovascular events in stable coronary heart disease patients with 8-year
      follow-up.
AB  - BACKGROUND: The clinical relevance of slightly increased circulating troponin
      concentrations in patients with stable coronary heart disease (CHD) several weeks
      after an acute event or CABG has not been fully evaluated. METHODS: Baseline
      plasma concentrations of troponin T were measured with a high-sensitivity assay
      (hs-cTnT) (Roche Elecsys) in a cohort of 1050 CHD patients from 30 to 70 years of
      age. The prognostic value of hs-cTnT on a combined cardiovascular disease (CVD)
      end point after adjustment for covariates was determined with Cox proportional
      hazards modeling. RESULTS: The median hs-cTnT concentration was 10.9 ng/L
      (interquartile range, 5.1-18.9 ng/L). Increased hs-cTnT concentrations were
      associated with an older age, history of hypertension and diabetes, more advanced
      coronary artery disease, and other CHD risk factors. Furthermore, hs-cTnT
      concentration was strongly correlated with N-terminal pro-B-type natriuretic
      peptide (NT-proBNP) and cystatin C (rho = 0.61, and rho = 0.32, respectively;
      both P values <0.0001). During a median follow-up of 8.1 years, 150 patients
      (14.3%) experienced a secondary CVD event. In a multivariate model, hs-cTnT was
      associated with a hazard ratio (HR) for secondary events of 2.83 (95% CI, 1.68
      4.79) when the extreme quartiles were compared. Further adjustment for cystatin
      C, NT-proBNP, and C-reactive protein attenuated this association only slightly
      (HR, 2.27; 95% CI, 1.31-3.95); P for trend < 0.002). ROC curve analysis of a
      clinical model that added hs-cTnT to a baseline model showed nonsignificant
      improvement in the area under the curve (0.69 vs 0.67), whereas the net
      reclassification improvement was 17.2% (P = 0.029). CONCLUSIONS: Slightly
      increased hs-cTnT concentrations in stable CHD patients are associated with
      several cardiovascular disorders and predict long-term CVD events.

PMID- 22634380
TI  - Numerical simulation of liquid velocity distribution in a sonochemical reactor.
AB  - Ultrasonically induced flow is an important phenomenon observed in a sonochemical
      reactor. It controls the mass transport of sonochemical reaction and enhances the
      reaction performance. In the present paper, the liquid velocity distribution of
      ultrasonically induced flow in the sonochemical reactor with a transducer at
      frequency of 490 kHz has been numerically simulated. From the comparison of
      simulation results and experimental data, the ultrasonic absorption coefficient
      in the sonochemical reactor has been evaluated. To simulate the liquid velocity
      near the liquid surface above the transducer, which is the main sonochemical
      reaction area, it is necessary to include the acoustic fountain shape into the
      computational domain. The simulation results indicate that the liquid velocity
      increases with acoustic power. The variation of liquid height also influences the
      behavior of liquid velocity distribution and the mean velocity above the
      transducer centre becomes a maximum when the liquid height is 0.4m. The liquid
      velocity decreases with increasing the transducer plate radius at the same
      ultrasonic power.

PMID- 22634381
TI  - Polyphenolic compounds are novel protective agents against lipid membrane damage
      by alpha-synuclein aggregates in vitro.
AB  - Cumulative evidence now suggests that the abnormal aggregation of the protein
      alpha-synuclein (alphaS) is a critical factor in triggering neurodegeneration in
      Parkinson's disease (PD). In particular, a fundamental pathogenetic mechanism
      appears to involve targeting of neuronal membranes by soluble oligomeric
      intermediates of alphaS, leading to their disruption or permeabilisation.
      Therefore, a model assay was developed in which fluorophore-loaded unilamellar
      vesicles were permeabilised by soluble oligomers, the latter formed by
      aggregation of human recombinant alphaS protein. The alphaS oligomers induced an
      impairment of membrane integrity similar to that of the pore-forming bacterial
      peptide gramicidin. The lipid vesicle permeabilisation assay was then utilised to
      screen 11 natural polyphenolic compounds, 8 synthetic N'-benzylidene
      benzohydrazide compounds and black tea extract for protection against membrane
      damage by wild-type and mutant (A30P, A53T) synuclein aggregates. A select group
      of potent inhibitory compounds included apigenin, baicalein, morin,
      nordihydroguaiaretic acid, and black tea extract. Structure-activity analysis
      further suggests that a 5,7-dihydroxy-chromen-4-one moiety appears to be
      favourable for the inhibition reaction. In conclusion, we have identified a group
      of polyphenols that can effectively hinder membrane damage by alphaS aggregates.
      These may serve as a viable source of lead compounds for the development and
      design of novel therapeutic agents in PD.

PMID- 22634382
TI  - TRPM7: a unique channel involved in magnesium homeostasis.
AB  - TRPM7 is a ubiquitously expressed cation channel with a fused alpha kinase
      domain. It is highly permeable to magnesium and calcium, and is negatively gated
      by intracellular Mg(2+) and Mg-ATP. Substrates for the TRPM7 kinase domain
      include annexinA1 and myosin IIA heavy chain, and there is evidence to suggest a
      functional interaction between the channel and kinase domains. Alterations in the
      expression and activity of TRPM7 have profound effects on cell proliferation and
      differentiation. Genetic deletion of TRPM7 in model systems demonstrates that
      this channel is critical for cellular growth and embryonic development. Here, we
      provide a brief overview of the activity of TRPM7 and the associated regulatory
      mechanisms. We will then discuss the biological functions of TRPM7, emphasizing
      its role in development and the potential pathophysiological significance of
      TRPM7 in neurological and cardiovascular disease.

PMID- 22634384
TI  - Effect of epistasis and linkage on fixation probability in three-locus models: an
      ancestral recombination-selection graph approach.
AB  - We study the probability of ultimate fixation of a single new mutant arising in
      an individual chosen at random at a locus linked to two other loci carrying
      previously arisen mutations. This is done using the Ancestral Recombination
      Selection Graph (ARSG) in a finite population in the limit of a large population
      size, which is also known as the Ancestral Influence Graph (AIG). An analytical
      expansion of the fixation probability with respect to population-scaled
      recombination rates and selection intensities is obtained. The coefficients of
      the expansion are expressed in terms of the initial state of the population and
      the epistatic interactions among the selected loci. Under the assumption of weak
      selection at tightly linked loci, the sign of the leading term, which depends on
      the signs of epistasis and initial linkage disequilibrium, determines whether an
      increase in recombination rates increases the chance of ultimate fixation of the
      new mutant. If mutants are advantageous, this is the case when epistasis is
      positive or null and the initial linkage disequilibrium is negative, which is an
      expected state in a finite population under directional selection. Moreover, this
      is also the case for a neutral mutant modifier coding for higher recombination
      rates if the same conditions hold at the selected loci. Under the same
      conditions, deleterious mutants are disfavored for ultimate fixation and neutral
      modifiers for higher recombination rates still favored. The recombination rates
      between the modifier locus and the selected loci do not come into play in the
      leading terms of the approximation for the fixation probability, but they do in
      higher-order terms.

PMID- 22634383
TI  - The NF-kappaB member p65 controls glutamine metabolism through miR-23a.
AB  - Cancer cells have elevated aerobic glycolysis that is termed the Warburg effect.
      But several tumor cells, including leukemic cells, also increase glutamine
      metabolism, which is initiated by glutaminase (GLS). The microRNA (miRNA) miR-23
      targets GLS mRNA and inhibits expression of GLS protein. Here we show that in
      human leukemic Jurkat cells the NF-kappaB p65 subunit binds to miR-23a promoter
      and inhibits miR-23a expression. Histone deacetylase (HDAC) inhibitors release
      p65-induced inhibition. Jurkat cells growing in glutamine decrease proliferation
      due to cell accumulation in G0/G1 phase. Nevertheless, cells get used to this new
      source of energy by increasing GLS expression, which correlates with an increase
      in p65 expression and its translocation to the nucleus, leading to a higher basal
      NF-kappaB activity. Jurkat cells overexpressing p65 show increase basal GLS
      expression and proliferate faster than control cells in glutamine medium.
      Overexpressing miR-23a in leukemic cells impaired glutamine use and induces
      mitochondrial dysfunction leading to cell death. Therefore, p65 activation
      decreases miR-23a expression, which facilitates glutamine consumption allowing
      leukemic cells to use this alternative source of carbon and favoring their
      adaptation to the metabolic environment.

PMID- 22634385
TI  - Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral
      tissues by ghrelin and 3-TRP-ghrelin.
AB  - Ghrelin is not only a modulator of feeding and energy expenditure but also
      regulates reproductive functions, CNS development and mood. Obesity and major
      depression are growing public health concerns which may derive, in part, from
      dysregulation of ghrelin feedback at brain regions regulating feeding and mood.
      We and others have previously reported that thyrotropin-releasing hormone (TRH,
      pGlu-His-Pro-NH(2)) and TRH-like peptides (pGlu-X-Pro-NH(2), where "X" can be any
      amino acid residue) have neuroprotective, antidepressant, anti-epileptic,
      analeptic, anti-ataxic, and anorectic properties. For this reason male Sprague
      Dawley rats were injected ip with 0.1mg/kg rat ghrelin or 0.9mg/kg 3-Trp-rat
      ghrelin. Twelve brain regions: cerebellum, medulla oblongata, anterior cingulate,
      posterior cingulate, frontal cortex, nucleus accumbens, hypothalamus, entorhinal
      cortex, hippocampus, striatum, amygdala, piriform cortex and 5 peripheral tissues
      (adrenals, testes, epididymis, pancreas and prostate) were analyzed. Rapid and
      profound decreases in TRH and TRH-like peptide levels (increased release)
      occurred throughout brain and peripheral tissues following ip ghrelin. Because
      ghrelin is rapidly deacylated in vivo we also studied 3-Trp-ghrelin which cannot
      be deacylated. Significant increases in TRH and TRH-like peptide levels following
      3-Trp-ghrelin, relative to those after ghrelin were observed in all brain regions
      except posterior cingulate and all peripheral tissues except prostate and testis.
      The rapid stimulation of TRH and TRH-like peptide release by ghrelin in contrast
      with the inhibition of such release by 3-Trp-TRH is consistent with TRH and TRH
      like peptides modulating the downstream effects of both ghrelin and unacylated
      ghrelin.

PMID- 22634387
TI  - Developmental causes of allometry: new models and implications for phenotypic
      plasticity and evolution.
AB  - Shapes change during development because tissues, organs, and various anatomical
      features differ in onset, rate, and duration of growth. Allometry is the study of
      the consequences of differences in the growth of body parts on morphology,
      although the field of allometry has been surprisingly little concerned with
      understanding the causes of differential growth. The power-law equation y =
      ax(b), commonly used to describe allometries, is fundamentally an empirical
      equation whose biological foundation has been little studied. Huxley showed that
      the power-law equation can be derived if one assumes that body parts grow with
      exponential kinetics, for exactly the same amount of time. In life, however, the
      growth of body parts is almost always sigmoidal, and few, if any, grow for
      exactly the same amount of time during ontogeny. Here, we explore the shapes of
      allometries that result from real growth patterns and analyze them with new
      allometric equations derived from sigmoidal growth kinetics. We use an extensive
      ontogenetic dataset of the growth of internal organs in the rat from birth to
      adulthood, and show that they grow with Gompertz sigmoid kinetics. Gompertz
      growth parameters of body and internal organs accurately predict the shapes of
      their allometries, and that nonlinear regression on allometric data can
      accurately estimate the underlying kinetics of growth. We also use these data to
      discuss the developmental relationship between static and ontogenetic
      allometries. We show that small changes in growth kinetics can produce large and
      apparently qualitatively different allometries. Large evolutionary changes in
      allometry can be produced by small and simple changes in growth kinetics, and we
      show how understanding the development of traits can greatly simplify the
      interpretation of how they evolved.

PMID- 22634386
TI  - Comparing participation rates between immunochemical and guaiac faecal occult
      blood tests: a systematic review and meta-analysis.
AB  - BACKGROUND: Biennial screening with faecal occult blood tests (FOBts) has been
      found to reduce colorectal cancer mortality. Faecal immunochemical tests (FITs)
      are superior to guaiac faecal occult blood tests (G-FOBts) due to their improved
      sensitivity and specificity. However the effectiveness of a screening programme
      depends highly on participation rates. The aim of this study was to review
      studies comparing guaiac faecal occult blood tests and faecal immunochemical
      tests, in terms of participation rates. METHODS: We searched PubMed and the
      Cochrane Library (2000-September 2011) to identify randomised control trials
      comparing guaiac faecal occult blood test with faecal immunochemical test
      participation rates. One author screened the titles and abstracts, and performed
      data extraction which was then checked by the other authors. Risk of bias in the
      included studies was also assessed. RESULTS: Seven studies met the eligibility
      criteria and were entered into a meta-analysis. Participation rates were
      significantly higher for individuals offered faecal immunochemical tests compared
      to those offered a guaiac faecal occult blood test (RR 1.21; 95% CI 1.09-1.33).
      Potential factors that could have influenced participation were discussed.
      CONCLUSIONS: Colorectal cancer screening programmes currently using guaiac faecal
      occult blood tests could improve participation rates by converting to faecal
      immunochemical tests. More research examining the acceptability of faecal
      immunochemical tests, from a patient perspective, is warranted.

PMID- 22634388
TI  - Excess heart rate and systolic blood pressure during psychological stress in
      relation to metabolic demand in adolescents.
AB  - Cardiovascular responses during exercise are matched to the increased metabolic
      demand, but this may not be the case during psychological stress. No studies to
      date have tested this hypothesis in youth. Fifty-four youth, ages 13-16 years
      completed two visits. Heart rate (HR), systolic blood pressure (SBP), and oxygen
      (O(2)) consumption were measured during a graded exercise test on one day and
      during psychological stress reactivity (star tracing, speech) on another day.
      Predicted HR and SBP values during psychological stress were calculated based on
      HR-O(2) and SBP-O(2) relationships calculated during graded exercise. At a given
      O(2) consumption, actual HR was greater (p<0.02) than predicted for all stress
      tasks. Actual SBP was greater (p<0.001) than predicted for all stress tasks. This
      was the first study to demonstrate that cardiovascular responses were in excess
      of what would be expected based on metabolic demand in youth.

PMID- 22634389
TI  - Approach-related left prefrontal EEG asymmetry predicts muted error-related
      negativity.
AB  - In two studies, we used electroencephalography (EEG) to test whether approach
      motivation-related brain activity would predict reduced sensitivity to negative
      outcomes. In both studies, participants (Study 1, N=26; Study 2, N=56) were first
      recorded for baseline EEG to measure approach-related left frontal EEG activity.
      They then completed either the color-naming Stroop task (Study 1) or the Multi
      Source Interference Task (Study 2) to measure error-related negativity (ERN), an
      event-related potential that has been associated with aversive motivation and
      distress. In both studies, higher leftward frontal EEG asymmetry predicted
      reduced ERN amplitude. Hierarchical regression analyses of the separate frontal
      nodes that comprised the asymmetry score further showed that left frontal
      activity predicted reduced ERN amplitude whereas right frontal activity predicted
      greater ERN amplitude. Results have implications for understanding emotion and
      motivation and for understanding the personal resilience associated with approach
      motivated states.

PMID- 22634390
TI  - [Intra-abdominal seroma and lymphopenia without leucopenia in a cancer patient.
      Geotrichum candidum infection].

PMID- 22634391
TI  - Comment on Folic acid improves inner ear vascularization in hyperhomocysteinemic
      mice, Hearing Research 2012, 284: 42-51 (Kundu, Munjal, N. Tyagi, Sen, A. Tyagi,
      S. Tyagi).

PMID- 22634392
TI  - Mesenchymal stem cells inhibit Th17 cell differentiation by IL-10 secretion.
AB  - Recent findings indicate that mesenchymal stem cells (MSCs) may act as a
      regulator of Th17 cell differentiation, however, the underlying mechanism is
      still under debate. To investigate the underlying mechanisms of MSCs' regulatory
      effect, mouse bone marrow-derived MSCs were cocultured with mouse
      CD4(+)CD25(low)CD44(low)CD62L(high) T cells in vitro, and the proportion of
      induced Th17 cells, cytokines secretion, and transcription factors expression
      were examined by flow cytometry, enzyme-linked immunosorbent assay, quantitative
      reverse transcription polymerase chain reaction, and Western blotting. For the
      first time, our results showed that bone marrow-derived MSCs were able to inhibit
      Th17 cell differentiation via interleukin (IL)-10 secretion as the Th17 cell
      proportion was significantly regained when IL-10 was neutralized, or expression
      of IL-10 by bone marrow-derived MSCs was downregulated by RNA interference
      technique. Furthermore, IL-10 may suppress expression of Rorgammat, the key
      transcription factor for Th17 cells, both by activating suppressor of cytokine
      signaling 3 through signal transducers and activators of transcription 5
      phosphorylation, and decreasing signal transducers and activators of
      transcription 3 binding, which is at the promoter of Rorgammat. Thus, our results
      demonstrate the inhibitory effect of MSCs on Th17 cells differentiation, and
      suggest increased IL-10 secretion might be the key factor.

PMID- 22634393
TI  - CML cells expressing the TEL/MDS1/EVI1 fusion are resistant to imatinib-induced
      apoptosis through inhibition of BAD, but are resensitized with ABT-737.
AB  - Chronic myeloid leukemia is the first disease in which the potential of molecular
      targeted therapy with tyrosine kinase inhibitors (TKIs) was realized. Despite
      this success, a proportion of patients, particularly with advanced disease, are,
      or become, resistant to this treatment. Overcoming resistance and uncovering the
      underlying mechanisms is vital for further improvement of clinical outcomes. Here
      we report the identification, development, and characterization of a novel
      chronic myeloid leukemia cell line carrying the additional chromosomal aberration
      t(3;12)(q26;p13) resulting in expression of the TEL/MDS1/EVI1 fusion protein,
      which is resistant to TKIs. Resistance to TKIs was overcome by the co
      administration of the BH3-mimetic, ABT-737. In addition, application of EVI1
      specific small interfering RNA decreased expression of the TEL/MDS1/EVI1 fusion,
      reduced resistance to imatinib, and increased sensitivity to ABT-737. Subsequent
      studies revealed a role for the BH3-only protein BAD, probably via a
      phosphoinositide 3-kinase/AKT-dependent pathway, as pharmacological inhibition of
      AKT could also resensitize cells to death from TKIs. These findings indicate a
      novel pathway of TKI resistance regulated by EVI1 proteins and provide a
      promising means for overcoming resistance in chronic myeloid leukemia and other
      hematological malignancies displaying EVI1 overexpression.

PMID- 22634394
TI  - Protein thiyl radical mediates S-glutathionylation of complex I.
AB  - Complex I is a critical site of O(2)(*-) production and the major host of
      reactive protein thiols in mitochondria. In response to oxidative stress, complex
      I protein thiols at the 51- and 75-kDa subunits are reversibly S
      glutathionylated. The mechanism of complex I S-glutathionylation is mainly
      obtained from insight into GSSG-mediated thiol-disulfide exchange, which would
      require a dramatic decline in the GSH/GSSG ratio. Intrinsic complex I S
      glutathionylation can be detected in the rat heart at a relatively high GSH/GSSG
      ratio (J. Chen et al., J. Biol. Chem. 285:3168-3180, 2010). Thus, we hypothesized
      that reactive thiyl radical is more likely to mediate protein S-glutathionylation
      of complex I. Here we employed immuno-spin trapping and tandem mass spectrometry
      (LC/MS/MS) to test the hypothesis in the 75-kDa subunit from S-glutathionylated
      complex I. Under the conditions of O(2)(*-) production in the presence of GSH, we
      detected complex I S-glutathionylation at Cys-226, Cys-367, and Cys-727 of the 75
      kDa subunit. Addition of a radical trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO),
      significantly decreased complex I S-glutathionylation and subsequently increased
      the protein radical adduct of complex I-DMPO as detected by immunoblotting using
      an anti-DMPO antibody. LC/MS/MS analysis indicated that Cys-226, Cys-554, and Cys
      727 were involved in DMPO binding, confirming that formation of the complex I
      thiyl radical mediates S-glutathionylation. LC/MS/MS analysis also showed that
      Cys-554 and Cys-727 were S-sulfonated under conditions of O(2)(*-) generation in
      the absence of DMPO. In myocytes (HL-1 cell line) treated with menadione to
      trigger mitochondrial O(2)(*-) generation, complex I protein radical and S
      glutathionylation were increased. Thus mediation of complex I S-glutathionylation
      by the protein thiyl radical provides a unique pathway for the redox regulation
      of mitochondrial function.

PMID- 22634395
TI  - Glutathione peroxidase 4 has a major role in protecting mitochondria from
      oxidative damage and maintaining oxidative phosphorylation complexes in gut
      epithelial cells.
AB  - Intake of the micronutrient selenium, which is incorporated into 25
      selenoproteins in humans, has been implicated in affecting risk of colorectal
      cancer. A genetic variant in the gene encoding the selenoprotein glutathione
      peroxidase 4 (GPX4) has been reported to influence colorectal cancer risk. In
      this study GPX4 expression was knocked down by 60% using RNA silencing and the
      effects were investigated using an unbiased transcriptomic analysis. Microarray
      analysis of the total Caco-2 cell transcriptome was carried out using Illumina
      HumanHT-12v3 beadchips and the data were validated by real-time PCR. Ingenuity
      Pathway Analysis showed that the major canonical pathways affected by GPX4
      knockdown were oxidative phosphorylation, ubiquinone biosynthesis, and
      mitochondrial dysfunction and the top two toxicological lists were mitochondrial
      dysfunction and oxidative stress. Western blotting and real-time PCR confirmed
      that knockdown affected target genes encoding components of respiratory complexes
      I, IV, and V as well as the protein apoptosis-inducing factor (AIF). GPX4
      knockdown increased levels of mitochondrial reactive oxygen species and oxidized
      lipid and decreased mitochondrial adenosine triphosphate levels and mitochondrial
      membrane potential. Time-course experiments showed that changes in AIF expression
      preceded those in the respiratory complexes. We conclude that in Caco-2 gut
      epithelial cells GPx4, through effects on AIF, plays a major role in maintaining
      the oxidative phosphorylation system and protecting mitochondria from oxidative
      damage.

PMID- 22634396
TI  - Bovine rod rhodopsin. 1. Bleaching by luminescence in vitro by recombination of
      radicals from polyunsaturated fatty acids.
AB  - Rod outer segments of photoreceptors are characterized by rhodopsin, a membrane
      protein surrounded by phospholipids containing a very high concentration of
      polyunsaturated fatty acids. These fatty acids can propagate free radicals,
      initiated by peroxidation, whose recombination is eventually associated with
      light emission as chemiluminescence. The results reported here indicate that this
      effect produces an isomerization of the retinal (bleaching effect) of the
      rhodopsin, similar to that induced by light in normal vision. In vitro
      experiments on detergent-suspended rod outer segments (RdOS) from bovine eyes,
      using an enzymatic source of radicals, xanthine/xanthine oxidase, were carried
      out. The results indicate that the proposed mechanism is likely, because they can
      show the bleaching of rhodopsin in RdOS, owing to its extraordinary sensitivity.
      Thus this mechanism is, also, a possible explanation for anomalous visual effects
      such as light flashes (phosphene-like) perceived by humans. The functionality of
      the rhodopsin in the RdOS was first tested by visible light. Rhodopsin
      reactivation after bleaching was obtained by adding cis-retinal to the
      suspension, demonstrating the reversibility of the bleaching process. A special
      experimental system was developed to observe the bleaching from luminescence by
      radical recombination, avoiding physical contact between the rod outer segment
      suspension and the radicals to prevent radical-induced damage and modifications
      of the delicate structure of the rod outer segment.

PMID- 22634397
TI  - Iniparib plus paclitaxel and carboplatin as initial treatment of advanced or
      recurrent uterine carcinosarcoma: a Gynecologic Oncology Group Study.
AB  - OBJECTIVE: To estimate the activity and tolerability of iniparib plus paclitaxel
      and carboplatin as initial therapy of uterine carcinosarcoma. METHODS: Eligible
      patients had advanced, persistent or recurrent carcinosarcoma of the uterus,
      measurable disease and no prior chemotherapy. Patients received paclitaxel 175
      mg/m(2) IV over 3h followed by carboplatin area under the curve (AUC)=six over 30
      min on day one of 21 day cycles plus iniparib 4 mg/kg IV over 1h twice weekly
      beginning on day one. Treatment continued until disease progression or adverse
      effects prohibited further therapy. Common Terminology Criteria for Adverse
      Events (CTCAE) v3.0 was used to grade adverse events. The primary endpoint was
      tumor response. The study was conducted with a 2-stage group sequential design,
      targeting 20 and 25 patients in each stage. The study was designed to distinguish
      between 45% versus 65% responding with alpha=10% and 90% power. RESULTS: Twenty
      two patients were entered onto the study with five excluded from analysis,
      leaving 17 evaluable for analysis. Treatment resulted in the expected hematologic
      and non-hematologic toxicities of the paclitaxel-carboplatin backbone. The
      observed proportion responding was 23.5% (4/17 patients). The two-sided, 90%
      confidence interval for the true probability of response was 8.5-46.1%. The
      required minimal number of responses to proceed to second stage was eight.
      CONCLUSIONS: Iniparib plus paclitaxel and carboplatin did not show significant
      activity to warrant further study. The rate of exclusion upon central pathology
      review (23%) suggests that review of pathology slides for confirmation of
      eligibility is important in this tumor type.

PMID- 22634398
TI  - Gastrulation and pre-gastrulation morphogenesis, inductions, and gene expression:
      similarities and dissimilarities between urodelean and anuran embryos.
AB  - Studies of meso-endoderm and neural induction and subsequent body plan formation
      have been analyzed using mainly amphibians as the experimental model. Xenopus is
      currently the predominant model, because it best enables molecular analysis of
      these induction processes. However, much of the embryological information on
      these inductions (e.g., those of the Spemann-Mangold organizer), and on the
      morphogenetic movements of inductively interacting tissues, derives from research
      on non-model amphibians, especially urodeles. Although the final body pattern is
      strongly conserved in vertebrates, and although many of the same developmental
      genes are expressed, it has become evident that there are individually diverse
      modes of morphogenesis and timing of developmental events. Whether or not this
      diversity represents essential differences in the early induction processes
      remains unclear. The aim of this review is to compare the gastrulation process,
      induction processes, and gene expressions between a urodele, mainly Cynops
      pyrrhogaster, and an anura, Xenopus laevis, thereby to clarify conserved and
      diversified aspects. Cynops gastrulation differs significantly from that of
      Xenopus in that specification of the regions of the Xenopus dorsal marginal zone
      (DMZ) are specified before the onset of gastrulation, as marked by blastopore
      formation, whereas the equivalent state of specification does not occur in Cynops
      until the middle of gastrulation. Detailed comparison of the germ layer structure
      and morphogenetic movements during the pre-gastrula and gastrula stages shows
      that the entire gastrulation process should be divided into two phases of
      notochord induction and neural induction. Cynops undergoes these processes
      sequentially after the onset of gastrulation, whereas Xenopus undergoes notochord
      induction during a series of pre-gastrulation movements, and its traditionally
      defined period of gastrulation only includes the neural induction phase.
      Comparing the structure, fate, function and state of commitment of each domain of
      the DMZ of Xenopus and Cynops has revealed that the true form of the Spemann
      Mangold organizer is suprablastoporal gsc-expressing endoderm that has notochord
      inducing activity. Gsc-expressing deep endoderm and/or superficial endoderm in
      Xenopus is involved in inducing notochord during pre-gastrulation morphogenesis,
      rather than both gsc- and bra-expressing tissues being induced at the same time.

PMID- 22634399
TI  - Ebselen inhibits iron-induced tau phosphorylation by attenuating DMT1 up
      regulation and cellular iron uptake.
AB  - Dysregulation of iron homeostasis is involved in the pathological process of
      Alzheimer's disease (AD). We have recently reported that divalent metal
      transporter 1 (DMT1) is upregulated in an AD transgenic mouse brain, and that
      silencing of DMT1, which reduces cellular iron influx, results in inhibition of
      amyloidogenesis in vitro, suggesting a potential target of DMT1 for AD therapy.
      In the present study, we tested the hypothesis that inhibition of DMT1 with
      ebselen, a DMT1 transport inhibitor, could affect tau phosphorylation. Human
      neuroblastoma SH-SY5Y cells were pre-treated with ebselen and then treated with
      ferrous sulfate (dissolved in ascorbic acid), and the effects of ebselen on tau
      phosphorylation and the relative signaling pathways were examined. Our results
      showed that ebselen decreased iron influx, reduced iron-induced ROS production,
      inhibited the activities of cyclin-dependent kinase 5 and glycogen synthase
      kinase 3beta, and ultimately attenuated the levels of tau phosphorylation at the
      sites of Thr205, Ser396 and Thr231. The present study indicates that the
      neuroprotective effect of ebselen on AD is not only related to its antioxidant
      activity as reported previously, but is also associated with a reduction in tau
      phosphorylation by inhibition of DMT1.

PMID- 22634400
TI  - Renin-angiotensin system inhibitors can suppress atrial fibrillation recurrence
      after encircling ipsilateral pulmonary vein isolation in patients with a non
      dilated left atrium.
AB  - INTRODUCTION: The purpose of this study was to investigate whether the effects of
      renin-angiotensin system inhibitors (RASIs) after encircling ipsilateral
      pulmonary veins isolation (EIPVsI) for atrial fibrillation (AF) differed between
      patients with non-dilated and dilated left atria. MATERIALS AND METHODS: We
      retrospectively studied 292 consecutive patients (mean age=61+/-11 years, 75%
      males) who underwent successful EIPVsI for paroxysmal or persistent AF. RASIs'
      effects were compared between the patients with a non-dilated left atrium of <40
      mm (n=178) and dilated left atrium of >=40 mm (n=114). RESULTS: During a mean
      follow-up period of 18.9+/-12.7 months, AF recurred in 38 (21.4%) and 45 (39.5%)
      patients with non-dilated and dilated left atria, respectively. A multivariate
      Cox proportional analysis revealed that treatment with RASIs (hazard ratio (HR)
      0.30, 95% confidence interval (CI) =0.13-0.66, p=0.003), the duration of AF (HR
      1.08/year, 95% CI=1.01-1.16, p=0.03), a history of hypertension (HR 2.86, 95%
      CI=1.21-6.85, p=0.02) and the left ventricular ejection fraction (HR 0.54/10%?,
      95% CI=0.34-0.87, p=0.01) were associated with AF recurrences in patients with a
      non-dilated left atrium. On the other hand, only the duration of AF (HR
      1.11/year, 95% CI=1.01-1.21, p=0.03) was associated with AF recurrences in those
      with a dilated LA, and RASIs had no effect on AF recurrences (p=0.65).
      CONCLUSIONS: RASIs suppressed AF recurrences after EIPVsI only in patients with a
      non-dilated left atrium.

PMID- 22634401
TI  - Comparative proteome analysis of Aspergillus oryzae 3.042 and A. oryzae 100-8
      strains: Towards the production of different soy sauce flavors.
AB  - Aspergillus oryzae plays a central role in soybean fermentation, particularly in
      its contribution to the flavor of soy sauce. We present a comparative assessment
      of the intracellular differences between wild-type strain 3.042 and mutant strain
      A100-8, at the proteome level. 522 different protein spots were identified by
      MALDI-TOF MS, with 134 spots being confirmed by MALDI-TOF MS/MS. Of these, 451
      were differentially expressed proteins (DEPs). There was at least a two-fold
      increase for 288 spots, and at least a two-fold decrease for 163 spots, in strain
      A100-8 when compared to 3.042. Further analysis showed that 63 of the more
      abundant proteins were involved in glycolysis and the citrate cycle; 43 more
      abundant proteins and 10 less abundant proteins were related to amino acid
      biosynthesis and metabolism; two of the more abundant proteins were involved in
      vitamin biosynthesis; and five of the more abundant proteins and four of the less
      abundant proteins were related to secondary metabolites. Moreover, quantitative
      real time PCR showed that the mRNA expression levels of six typical genes we
      selected were consistent with changes in protein expression. We postulate that
      there may be a relationship between DEPs and the flavor formation mechanism in A.
      oryzae.

PMID- 22634402
TI  - Sulfenylated proteins in the Medicago truncatula-Sinorhizobium meliloti
      symbiosis.
AB  - Reactive oxygen species such as hydrogen peroxide (H(2)O(2)), play a crucial role
      as signaling molecules in the establishment and functioning of the nitrogen
      fixing legume-Rhizobium symbiosis. The regulation of protein function through
      oxidative modification has emerged as an important molecular mechanism modulating
      various biological processes. Protein cysteine residues are known to be sensitive
      targets of H(2)O(2), in a posttranslational modification called sulfenylation. We
      trapped and identified sulfenylated proteins in the Medicago truncatula
      Sinorhizobium meliloti symbiosis, by combining the use of chemical and genetic
      probes with mass spectrometry analysis. We identified 44 M. truncatula proteins
      sulfenylated in inoculated roots (two days post infection, 2dpi) and 65 such
      proteins in the functioning symbiotic organ, the nodule (four weeks post
      infection, 4wpi); 18 proteins were identified at both time points. However, the
      largest functional groups at 2dpi and 4wpi were different: redox state-linked
      proteins early in the interaction and proteins involved in amino-acid and
      carbohydrate metabolism in the nodule. Twenty proteins from S. meliloti,
      including some directly involved in nitrogen fixation, were also identified as
      sulfenylated. These results suggest that sulfenylation may regulate the activity
      of proteins playing major roles in the development and functioning of the
      symbiotic interaction.

PMID- 22634403
TI  - Probe-based chemical modulations of tissues for IMS.
AB  - Chemical modulation imaging over a tissue is gaining momentum in the field of
      mass spectrometry. Some endogenous or exogenous compounds present in a tissue can
      be visualized by imaging mass spectrometry after chemical derivatization. This
      approach gives researchers the possibility to elude chemical interferences in
      components of the tissues, such as lipids or salts, as well as interferences
      caused by the matrix. The use of primary and secondary antibodies, the chemical
      derivatization of peptides and small molecules, and the use of (18)O labeling are
      various examples reviewed in this article to demonstrate the importance and
      potential of this emerging aspect of imaging mass spectrometry.

PMID- 22634404
TI  - Cyclosporin A suppresses prostate cancer cell growth through CaMKKbeta/AMPK
      mediated inhibition of mTORC1 signaling.
AB  - Cyclosporin A (CsA) has antitumor effects on various cancers including prostate
      cancer. However, its antitumor mechanism is poorly understood. In this study, we
      showed that AMP-activated protein kinase (AMPK) mediates the antitumor effect of
      CsA on prostate cancer cells. CsA attenuated cell growth by inducing a G1 arrest
      through the inhibition of mTOR complex 1 (mTORC1) signaling. In this context, Akt
      was paradoxically activated downstream of the EGF receptor (EGFR)-mediated
      increase in phosphatidylinositol 3,4,5-trisphosphate (PIP3) production. However,
      CsA also caused a Ca2+/calmodulin-dependent protein kinase kinase beta
      (CaMKKbeta)-dependent activation of AMPK, which inhibits mTORC1 signaling; this
      led to ineffective Akt signaling. An EGFR or Akt inhibitor increased the growth
      suppressive activity of CsA, whereas the combination of an AMPK inhibitor and CsA
      markedly rescued cells from the G1 arrest and increased cell growth. These
      results provide novel insights into the molecular mechanisms of CsA on cancer
      signaling pathways.

PMID- 22634406
TI  - Spectroscopic, thermal and mechanical studies on 4-methylanilinium p
      toluenesulfonate - a new organic NLO single crystal.
AB  - Bulk crystals of newly identified organic nonlinear optical material 4
      methylanilinium p-toluenesulfonate (PMPT) were grown by slow evaporation solution
      growth method using ethanol as a solvent. It crystallizes in monoclinic system
      with a noncentrosymmetric space group P2(1). The formation of the title compound
      was confirmed through microanalysis, X-ray diffraction and density measurements.
      The proton positions and functional groups have been identified and confirmed
      through nuclear magnetic resonance and Fourier transform infrared spectrums
      respectively. Optical properties are determined by UV-Visible and
      photoluminescence spectroscopic studies to explore its efficacy towards device
      fabrications. Thermal studies exhibited that the newly obtained PMPT crystals are
      stable up to 199  degrees C. Its mechanical strength was studied by Vickers micro
      hardness studies.

PMID- 22634405
TI  - Interaction of pseudolaric acid B with the colchicine site of tubulin.
AB  - We purified pseudolaric acid B (PAB) from the root and stem bark of Pseudolarix
      kaempferi (Lindl.) Gorden. Confirming previous findings, we found that the
      compound had high nanomolar IC50 antiproliferative effects in several cultured
      cell lines, causing mitotic arrest and the disappearance of intracellular
      microtubules. PAB strongly inhibited tubulin assembly (IC50, 1.1 MUM) but weakly
      inhibited the binding of colchicine to tubulin, as demonstrated by fluorescence
      and with [3H]colchicine. Kinetic analysis demonstrated that the mechanism of
      inhibition was competitive, with an apparent K(i) of 12-15 MUM. Indirect studies
      demonstrated that PAB bound rapidly to tubulin and dissociated more rapidly from
      tubulin than the colchicine analog 2-methoxy-5-(2',3',4'
      trimethoxyphenyl)tropone, whose complex with tubulin is known to have a half-life
      of 17s at 37  degrees C. We modeled PAB into the colchicine site of tubulin,
      using the crystal structure 1SA0 that contains two alphabeta-tubulin
      heterodimers, both bound to a colchicinoid and to a stathmin fragment. The
      binding model of PAB revealed common pharmacophoric features between PAB and
      colchicinoids, not readily apparent from their chemical structures.

PMID- 22634407
TI  - Characterization and optical properties of novel unsymmetrical stilbene-based
      1,3,4-oxadiazole derivatives.
AB  - A series of novel unsymmetrical stilbene-based 1,3,4-oxadiazole derivatives were
      efficiently synthesized by a four-pots reaction sequence. All of the title
      compounds were characterized by MS, (1)H-NMR and elemental analysis. UV-Vis
      absorption and fluorescence emission spectra of the compounds were investigated
      in dilute chloroform solution; the compounds exhibit strong blue-green
      fluorescence ranged from 397 to 499 nm and show potential for application in
      organic optical materials.

PMID- 22634408
TI  - Combining the isoabsorptive point in the ratio spectrum and the smart ratio
      difference methods for a single step determination of compounds with overlapped
      spectra.
AB  - A new method significantly advantageous over the conventional spectrophotometric
      methods regarding simplicity, minimal data processing and applicability was
      developed. The new method is based on the fact that isoabsorptive points whenever
      present in an absorption spectrum will be retained even after division by a one
      component as a divisor in the ratio spectrum, in addition to a smart modification
      of the conventional ratio derivative and ratio subtraction methods. This modified
      method though simpler, enabled wider range of applications. The proposed method
      was applied for the analysis of brimonidine and timolol in laboratory prepared
      mixtures with mean percentage recoveries 100.64 +/- 1.10 and 100.96 +/- 1.16,
      respectively, and in their pharmaceutical formulation with mean percentage
      recoveries 100.88 +/- 0.34 and 100.84 +/- 0.72, respectively. The suggested
      method was validated according to USP guidelines and can be applied for routine
      analysis in quality control laboratories.

PMID- 22634409
TI  - Electrochemistry and DFT simulation of optical spectra of N-ferrocenoyl-N'-omega
      decenoyl-ethylenediamine.
AB  - A new hybrid organic-inorganic chromophore based on ferrocene was synthesized. In
      addition to a detailed synthesis description the article describes complex
      quantum chemical and experimental (UV-VIS and electrochemical) studies of the
      redox and chromophore characteristics. The properties studied include the
      diffusion coefficient as well as solvatochromic effects in solvents differing in
      polarity, namely dichloromethane, propylene carbonate and acetonitrile. The
      experimental results are discussed within a framework of theoretical description
      at the DFT and TDDFT (6-31G(df,p)) levels of theory, with the PCM solvation
      model. Accuracy of B3LYP and BLYP functionals in reproducing orbital energy
      levels and optical transitions of the title molecule is briefly discussed.

PMID- 22634410
TI  - Studies on the photochemical behavior of N-salicylidenaniline in chloroform.
AB  - An N-salicylidenaniline (SA), compound 1 with 15-crown-5 moiety, was synthesized.
      The time-dependent NMR was used to track its photochromic process. The
      experimental results showed that ultraviolet irradiation would lead compound 1 to
      decompose into the corresponding salicylaldehyde and amine in chloroform
      solution, instead of experiencing a photochromic process. By the same method, the
      reported photochromic results of other SAs were also corrected.

PMID- 22634411
TI  - 3-Amino-1,2,4-triazolium ion in [24(3at)]Cl and [24(3at)]2SnCl6.H2O. Comparative
      X-ray, vibrational and theoretical studies.
AB  - Crystal structures of 3-amino-1,2,4-triazolium chloride and bis(3-amino-1,2,4
      triazolium) hexachloridostannate monohydrate were determined by means of X-ray
      single crystal diffraction. The route of protonation of organic molecule and
      tautomer equilibrium constants for the cationic forms were calculated using
      B3LYP/6-31G* method. The most stable protonated species is 2,4-H(2)-3-amino-1,2,4
      triazolium ion, 24(3at)(+). Very good agreement between theoretical and
      experimental frequencies was achieved due to very weak interactions existing in
      studied compounds. Significantly weaker intermolecular interactions are found in
      [24(3at)](2)SnCl(6).H(2)O than in [24(3at)]Cl. The differences in strength of
      interactions are manifested in red and blue shifts for stretching and bending
      motions, respectively. PED calculations show that for 24(3at)(+) ion the
      stretching type of motion of two N(ring)H bonds is independent, whereas bending
      is coupled.

PMID- 22634412
TI  - Effects of Mn doping on surface enhanced Raman scattering properties of TiO2
      nanoparticles.
AB  - TiO(2) and Mn-doped TiO(2) (1%, 3% and 5%) nanoparticles (NPs) were synthesized
      by a sol-hydrothermal method for surface-enhanced Raman spectroscopy study. When
      using the 4-mercaptobenzoic acid (4-MBA) as the probing molecule, optimum SERS
      signals were observed on the Mn-TiO(2) (3%) samples. On the 3% Mn doped TiO(2)
      substrate, 4-MBA molecules exhibit a higher SERS intensity by a factor of six as
      compared with the native enhancement of 4-MBA adsorbed on pure TiO(2) NPs. The
      possible mechanism for the phenomena is also discussed. This study opens up a new
      dimension for the family of SERS substrates.

PMID- 22634413
TI  - Fluorescent sensor based on a novel conjugated polyfluorene derivative.
AB  - A novel water-soluble polyfluorene derivative, poly[(9,9-bis(3'-((N,N
      dimethylamino)N-ethylammonium)propyl)-2,7-fluorene)-alt-2,7-(9,9-p
      divinylbenzene)]dibromide (P-2) was synthesized by the palladium-catalyzed Suzuki
      coupling reaction and it's quaternized ammonium polyelectrolyte derivatives was
      obtained through a postpolymerization treatment on the terminal amino groups. The
      electrochemical and optical properties of the copolymers was fully investigated.
      The results showed that the new polyfluorene derivative had high electronic
      conductivity and strong fluorescence, therefore it had good potential to be used
      in chemical and biological sensors, as shown in optical sensing of bovine albumin
      (BSA) in this study.

PMID- 22634414
TI  - Intermolecular hydrogen bonds in hetero-complexes of biologically active aromatic
      molecules probed by the methods of vibrational spectroscopy.
AB  - By the methods of vibrational spectroscopy (Infrared and Raman) the investigation
      of the hetero-association of biologically active aromatic compounds: flavin
      mononucleotide (FMN), ethidium bromide (EB) and proflavine (PRF) was performed in
      aqueous solutions. It was shown that between the functional groups (CO and NH(2))
      the intermolecular hydrogen bonds are formed in the hetero-complexes FMN-EB and
      FMN-PRF, additionally stabilizing these structures. An estimation of the enthalpy
      of N-bonding obtained from experimental shifts of carbonyl vibrational
      frequencies has shown that the H-bonds do not dominate in the magnitude of
      experimentally measured total enthalpy of the hetero-association reactions. The
      main stabilization is likely due to intermolecular interactions of the molecules
      in these complexes and their interaction with water environment.

PMID- 22634415
TI  - FT-IR study on interactions between medroxyprogesterone acetate and solvent in
      CHCl3/cyclo-C6H12 and CCl4/cyclo-C6H12 binary solvent systems.
AB  - The intermolecular interactions between medroxyprogesterone acetate (MPA) and
      CHCl(3) and CCl(4) solvent in CHCl(3)/cyclo-C(6)H(12) and CCl(4)/cyclo-C(6)H(12)
      binary solvent systems have been studied by Fourier transform infrared
      spectroscopy (FT-IR). The experimental results showed that there are hydrogen
      bonding interactions between oxygen atoms of all carbonyl groups in MPA and
      hydrogen atom of CHCl(3) so as to form 1:3 complex of MPA with CHCl(3) and
      produce three new absorption bands at 1728.9-1736.1, 1712.7-1717.4 and 1661.9
      1673.8 cm(-1), respectively. And, 1:1 complex of MPA with CCl(4) is formed in
      CCl(4)/cyclo-C(6)H(12) binary solvent as a result of hydrogen bonding interaction
      between C3 carbonyl group and empty d-orbital in chlorine atom of CCl(4) leading
      to producing new absorption band at 1673.2-1674.2 cm(-1). However, all free
      carbonyl and associated carbonyl stretching vibrations of MPA in CHCl(3)/cyclo
      C(6)H(12) and CCl(4)/cyclo-C(6)H(12) binary solvent systems shift to lower
      wavenumbers with the increasing of volume fraction of CHCl(3) and CCl(4) in
      binary solvent systems owing to the dipole-dipole interaction and the dipole
      induced dipole interaction between MPA and solvents.

PMID- 22634416
TI  - First analytical evidences of precious colourants on Mediterranean illuminated
      manuscripts.
AB  - Two Byzantine VI century manuscripts known as Vienna Dioskurides and Vienna
      Genesis, held in the Austrian National Library at Vienna, were analysed with in
      situ non-invasive techniques. Raman spectroscopy, UV-Vis diffuse reflectance
      spectrophotometry with optic fibres and X-ray fluorescence spectrometry were used
      to characterise the palette of these early Middle Ages manuscripts. The
      analytical study was performed to have a better knowledge on the colourants used
      by ancient miniature painters, a subject known more on the basis of traditional
      sources (i.e. medieval treatises) than of analytical evidences. Indeed these
      illuminated manuscripts are, to the authors' knowledge, among the oldest ever
      being analysed, so that the colourants found in them can be considered among the
      oldest evidences of their use. The main feature of Vienna Dioskurides and Vienna
      Genesis palettes is their richness, exemplified by the simultaneous presence of
      gold and ultramarine blue; in Vienna Dioskurides cinnabar is also present.
      Information regarding ultramarine blue is surprising, being the analytical
      evidence of the use of this precious pigment at least three centuries before its
      use in Western manuscripts, a feature justified by the fact that the Byzantine
      Empire was the dominant culture in early Middle Ages in the Mediterranean World.
      Other colourants include azurite and indigo, red lead, orpiment, red and yellow
      ochres, while a mixture of blue and yellow colourants, known as vergaut, was used
      to render green hues. Organic colourants were also used, such as madder and
      Tyrian purple, the latter employed to dye the parchment of Vienna Genesis.

PMID- 22634417
TI  - Determination of emodin by hexadecyl trimethyl ammonium bromide sensitized
      fluorescence quenching method of the derivatives of calix[4]arene.
AB  - The fluorescence quenching effect of emodin (EMO) on the derivatives of p-tert
      butyl-calix[4]arene with o-phenanthroline (TBCP) in 1.0% hexadecyl trimethyl
      ammonium bromide (CTAB) medium was investigated. The fluorescence of TBCP was
      quenched by EMO due to the formation of the weak fluorescent inclusion complex
      (EOM-TBCP), and the fluorescence quenching (DeltaF=F(TBCP)-F(EMO-TBCP)) was
      sensitized in CTAB. Under the optimal conditions, the linear range of calibration
      curve for the determination of EMO was 1.17-23.40 MUg/mL. The detection limit
      estimated and RSD was 0.34 MUg/mL, 3.63% (n=3, c=4.74 MUg/mL). The quantum yield
      Y(u) of TBCP was approximately 2.0 times higher in the presence of CTAB than that
      in the absence of CTAB. The method has been applied for the determination of EMO
      in samples with satisfactory results.

PMID- 22634418
TI  - Investigation the interaction of Daphnin with human serum albumin using optical
      spectroscopy and molecular modeling methods.
AB  - The interaction between Daphnin with human serum albumin has been studied for the
      first time by spectroscopic methods including fluorescence quenching technology,
      circular dichroism (CD) spectroscopy and Fourier transform infrared (FT-IR)
      spectroscopy under simulative physiological conditions. The results of
      fluorescence titration revealed that Daphnin can quench the intrinsic
      fluorescence of HSA by static quenching and there is a single class of binding
      site on HSA. In addition, the studies of CD spectroscopy and FT-IR spectroscopy
      showed that the protein secondary structure changed with increases of alpha
      helices at the drug to protein molar ratio of 2. Furthermore, the thermodynamic
      functions DeltaH(0) and DeltaS(0) for the reaction were calculated to be 11.626
      kJ mol(-1) and 118.843 J mol(-1)K(-1) according to Van't Hoff equation. The
      thermodynamic parameters (DeltaH(0) and DeltaS(0)) and the molecular modeling
      study indicated that hydrophobic force played an important role to stabilize the
      Daphnin-HSA complex, and Daphnin could bind within the subdomain IIA of the HSA.

PMID- 22634419
TI  - Vibrational spectroscopic study of multianion mineral clinotyrolite
      Ca2Cu9[(As,S)O4]4(OH)10.10(H2O).
AB  - The molecular structure of the mixed anion mineral clinotyrolite
      Ca(2)Cu(9)[(As,S)O(4)](4)(OH)(10).10(H(2)O) has been determined by the
      combination of Raman and infrared spectroscopy. Characteristic bands associated
      with arsenate, sulphate and hydroxyl units are identified. Broad bands in the OH
      stretching region are observed and are resolved into component bands. Estimates
      of hydrogen bond distances were made using a Libowitzky function and both short
      and long hydrogen bonds are identified. Two intense Raman bands at 842 and ~796
      cm(-1) are assigned to the nu(1) (AsO(4))(3-) symmetric stretching and nu(3)
      (AsO(4))(3-) antisymmetric stretching modes. The comparatively sharp Raman band
      at 980 cm(-1) is assigned to the nu(1) (SO(4))(2-) symmetric stretching mode and
      a broad Raman spectral profile centred upon 1100 cm(-1) is attributed to the
      nu(3) (SO(4))(2-) antisymmetric stretching mode.

PMID- 22634420
TI  - Sex steroid synthesis in human skin in situ: the roles of aromatase and
      steroidogenic acute regulatory protein in the homeostasis of human skin.
AB  - Sex steroids have been known to play important roles in the homeostasis of human
      skin, but little is known about their biosyntheses in that tissue. In this study,
      we characterized the correlation between the concentrations of sex steroids and
      the expression levels of the factors involved in their synthesis or metabolism in
      human skin. The expression levels of aromatase (ARO) and steroidogenic acute
      regulatory protein (StAR) were positively correlated with estrogens and
      testosterone concentrations, respectively. We demonstrated that estrogen
      synthesis was markedly decreased by ARO inhibitor and that skins with higher ARO
      expression had thicker elastic fibers than those with lower ARO expression. While
      pregnenolone and testosterone concentrations were increased by cholesterol
      administration to epidermal keratinocytes. Scalp skin with higher StAR expression
      was cleared to have significantly fewer hair follicles than that with lower
      expression. Our results suggest that the status of ARO and StAR contribute to
      estrogen synthesis in situ, especially for the regulation of elastic fiber
      formation, and to testosterone synthesis, which may be associated with hair
      growth, respectively.

PMID- 22634421
TI  - Reference repulsion in the categorical perception of biological motion.
AB  - Perceiving biological motion is important for understanding the intentions and
      future actions of others. Perceiving an approaching person's behavior may be
      particularly important, because such behavior often precedes social interaction.
      To this end, the visual system may devote extra resources for perceiving an
      oncoming person's heading. If this were true, humans should show increased
      sensitivity for perceiving approaching headings, and as a result, a repulsive
      perceptual effect around the categorical boundary of leftward/rightward motion.
      We tested these predictions and found evidence for both. First, observers were
      especially sensitive to the heading of an approaching person; variability in
      estimates of a person's heading decreased near the category boundary of
      leftward/rightward motion. Second, we found a repulsion effect around the
      category boundary; a person walking approximately toward the observer was
      perceived as being repelled away from straight ahead. This repulsive effect was
      greatly exaggerated for perception of a very briefly presented person or
      perception of a chaotic crowd, suggesting that repulsion may protect against
      categorical errors when sensory noise is high. The repulsion effect with a crowd
      required integration of local motion and human form, suggesting an origin in high
      level stages of visual processing. Similar repulsive effects may underlie
      categorical perception with other social features. Overall, our results show that
      a person's direction of walking is categorically perceived, with improved
      sensitivity at the category boundary and a concomitant repulsion effect.

PMID- 22634422
TI  - Recommendations for safety testing with the in vivo comet assay.
AB  - While the in vivo comet assay increases its role in regulatory safety testing,
      deliberations about the interpretation of comet data continue. Concerns can arise
      regarding comet assay publications with limited data from non-blind testing of
      positive control compounds and using protocols (e.g. dose concentrations, sample
      times, and tissues) known to give an expected effect. There may be a tendency
      towards bias when the validation or interpretation of comet assay data is based
      on results generated by widely accepted but non-validated assays. The greatest
      advantages of the comet assay are its sensitivity and its ability to detect
      genotoxicity in tissues and at sample times that could not previously be
      evaluated. Guidelines for its use and interpretation in safety testing should
      take these factors into account. Guidelines should be derived from objective
      review of data generated by blind testing of unknown compounds dosed at non-toxic
      concentrations and evaluated in a true safety-testing environment, where the
      experimental design and conclusions must be defensible. However, positive in vivo
      comet findings with such compounds are rarely submitted to regulatory agencies
      and this data is typically unavailable for publication due to its proprietary
      nature. To enhance the development of guidelines for safety testing with the
      comet assay, and with the permission of several sponsors, this paper presents and
      discusses relevant data from multiple GLP comet studies conducted blind, with
      unknown pharmaceuticals and consumer products. Based on these data and the
      lessons we have learned through the course of conducting these studies, I suggest
      significant adjustments to the current conventions, and I provide recommendations
      for interpreting in vivo comet assay results in situations where risk must be
      evaluated in the absence of carcinogenicity or clinical data.

PMID- 22634424
TI  - Aspergillus fumigatus calcineurin interacts with a nucleoside diphosphate kinase.
AB  - The Ca(2+)-calcineurin pathway affects virulence and morphogenesis in filamentous
      fungi. Here, we identified 37 CalA-interacting proteins that interact with the
      catalytic subunit of calcineurin (CalA) in Aspergillus fumigatus, including the
      nucleoside diphosphate kinase (SwoH). The in vivo interaction between CalA and
      SwoH was validated by bimolecular fluorescence complementation. A. fumigatus swoH
      is an essential gene. Therefore, a temperature-sensitive conditional mutant
      strain with a point mutation in the active site, SwoH(V83F), was constructed,
      which demonstrated reduced growth and increased sensitivity to elevated
      temperatures. The SwoH(V83F) mutation did not cause a loss in virulence in the
      Galleria mellonella infection model. Taken together these results imply that CalA
      interacts with SwoH.

PMID- 22634423
TI  - IL-17 and gammadelta T-lymphocytes play a critical role in innate immunity
      against Nocardia asteroides GUH-2.
AB  - The early host response during pulmonary nocardiosis is highly dependent on
      neutrophils and the successful clearance of bacteria in tissue. The data
      presented in this study showed that IL-17 mediated the neutrophil response
      following intranasal inoculation with Nocardia asteroides strain GUH-2. Flow
      cytometry revealed that neutrophil levels in C57BL/6 mice were increased by day 1
      post inoculation and remained elevated until day 3, during which time the
      majority of bacterial clearance occurred. Intracellular cytokine staining for IL
      17 showed a 3.5- to 5-fold increase in IL-17 producing T-lymphocytes that were
      predominately comprised by CD4(-)CD8(-) gammadelta T-lymphocytes. The importance
      of IL-17 and gammadelta T-cells was determined by the in vivo administration of
      antibody, capable of blocking IL-17 binding or TCR delta, respectively.
      Neutralization of either IL-17 or gammadelta T-cells in Nocardia treated mice
      resulted in attenuated neutrophil infiltration. Paralleling this impaired
      neutrophil recruitment, nearly a 10-fold increase in bacterial burden was
      observed in both anti-IL-17 and anti-TCR delta treated animals. Together, these
      data indicate a protective role for IL-17 and suggest that IL-17 producing
      gammadelta T-lymphocytes contribute to neutrophil infiltration during pulmonary
      nocardiosis.

PMID- 22634425
TI  - Sun protection and vitamin D status in an Australian subtropical community.
AB  - OBJECTIVE: Claims have been made that sun protection may negatively affect
      vitamin D status, but very few data are available about whether this applies to
      people in uncontrolled settings. METHOD: In 1996 we measured 25(OH)-vitamin D
      concentrations in 1113 adults in Nambour, a subtropical community, who reported
      their concurrent sun protection behaviours in a skin cancer prevention trial.
      Estimates were adjusted for time outdoors, vitamin D intake and other factors
      known to affect vitamin D status. RESULTS: Persons who tended to stay in the
      shade had lower vitamin D levels than those who never stayed in the shade (62.5
      vs. 68.8 nmol/L respectively, p=0.01), and this association remained in persons
      who spent less than 50% (p=0.02) but not in those who spent more than 50% of
      their time outdoors. Wearing a hat, long sleeves, sunglasses and use of sunscreen
      or umbrella were not associated with vitamin D status after adjustments,
      including after stratification by time outdoors. CONCLUSION: Sun protection
      behaviour to reduce the risk of skin cancer can be maintained without affecting
      vitamin D serum status, although consistently seeking shade when spending less
      than 50% of daytime outdoors is associated with lower vitamin D levels.

PMID- 22634426
TI  - Quality, originality, and significance of the 1939 "Tobacco consumption and lung
      carcinoma" article by Mueller, including translation of a section of the paper.
AB  - BACKGROUND: The 1939 article "Tobacco consumption and lung carcinoma" by Mueller
      has been praised for its quality and its originality but is still not available
      in English. METHODS: Summary of the 29-page long paper and translation of part of
      its investigative section. Re-analysis of the clinical and smoking
      characteristics of the lung cancer cases. Comparison with pre-1945 case-control
      studies and a similar but prior tobacco and cancer report. RESULTS: The article
      primarily consists of a detailed description of the smoking, clinical and
      occupational characteristics of 96, mostly dead, lung cancer cases. Occupation
      and the flu are discussed for the cases only. The paper makes unexplained
      assumptions about the smoking habits of 20 cases and is silent about the
      sampling, recruitment and interview modes of the "healthy" subjects, supposed to
      reflect "normal tobacco consumption." The dearth of methodological information
      distinguishes this paper from case-control studies published before 1939. Major
      selection and differential misclassification cannot be ruled out. CONCLUSION:
      Access to the 1939 Mueller article is provided for non-German speakers. The
      quality of the group comparison was modest and it did not add qualitatively new
      knowledge compared to a report published 8 years earlier.

PMID- 22634427
TI  - Area-based socioeconomic environment, obesity risk behaviours, area facilities
      and childhood overweight and obesity: socioeconomic environment and childhood
      overweight.
AB  - OBJECTIVE: The objective of this study is to evaluate whether the relation
      between area-based socioeconomic environment and childhood obesity can be
      explained by household socioeconomic position, obesity-related risk behaviours
      and area facilities. METHODS: Two indicators of socioeconomic environment based
      on wealth and deprivation were estimated in a sample of 4529 Spanish children and
      adolescents in 2006. Multilevel logit models were used to calculate the relation
      between each indicator and obesity. RESULTS: After adjusting for socioeconomic
      position and risk behaviours, no relation was observed between wealth and
      overweight; however, obesity prevalence was 1.45 times higher in subjects living
      in areas with lower wealth than in those living in areas with higher wealth.
      After adjusting for these variables, the prevalence of overweight and obesity in
      subjects living in deprived areas was, respectively, 1.26 and 1.63 higher than in
      those living in non-deprived areas. There was a graded association between number
      of sports facilities and prevalence of physical inactivity, but no relation was
      found between the price of fruits and vegetables and frequency of consumption.
      CONCLUSION: The relation of socioeconomic environment with childhood obesity
      could not be explained by household socioeconomic position or obesity-related
      risk behaviours. Availability of sport facilities may mediate this relation.

PMID- 22634428
TI  - Cultured Muller cells from mammals can synthesize and accumulate retinyl esters.

PMID- 22634429
TI  - MAGE-A antigens as targets in tumour therapy.
AB  - MAGE-A proteins constitute a sub-family of Cancer-Testis Antigens which are
      expressed mainly, but not exclusively, in germ cells. They are also expressed in
      various human cancers where they are associated with, and may drive, malignancy.
      MAGE-A proteins are highly immunogenic and are considered as potential targets
      for cancer vaccines and/or immuno-therapy. Moreover, recent advances in our
      understanding of their molecular pathology have revealed interactions that offer
      potential as therapeutic targets. Here we review recent progress in this area and
      consider how these interactions might be exploited, especially for the treatment
      of malignant cancers for which available treatments are inadequate.

PMID- 22634430
TI  - Molecular control of oogenesis.
AB  - Oogenesis is a complex process regulated by a vast number of intra- and extra
      ovarian factors. Oogonia, which originate from primordial germ cells, proliferate
      by mitosis and form primary oocytes that arrest at the prophase stage of the
      first meiotic division until they are fully-grown. Within primary oocytes,
      synthesis and accumulation of RNAs and proteins throughout oogenesis are
      essential for oocyte growth and maturation; and moreover, crucial for developing
      into a viable embryo after fertilization. Oocyte meiotic and developmental
      competence is gained in a gradual and sequential manner during folliculogenesis
      and is related to the fact that the oocyte grows in interaction with its
      companion somatic cells. Communication between oocyte and its surrounding
      granulosa cells is vital, both for oocyte development and for granulosa cells
      differentiation. Oocytes depend on differentiated cumulus cells, which provide
      them with nutrients and regulatory signals needed to promote oocyte nuclear and
      cytoplasmic maturation and consequently the acquisition of developmental
      competence.The purpose of this article is to summarize recent knowledge on the
      molecular aspects of oogenesis and oocyte maturation, and the crucial role of
      cumulus-cell interactions, highlighting the valuable contribution of experimental
      evidences obtained in animal models. This article is part of a Special Issue
      entitled: Molecular Genetics of Human Reproductive Failure.

PMID- 22634431
TI  - Outcome of accidental hypothermia with or without circulatory arrest: experience
      from the Danish Praesto Fjord boating accident.
AB  - BACKGROUND: Resuscitation guidelines for the treatment of accidental hypothermia
      are based primarily on isolated cases. Mortality rates are high despite
      aggressive treatment aimed at restoring spontaneous circulation and normothermia.
      METHODS: The present report is based on a boating accident where 15 healthy
      subjects (median age 16 (range 15-45) years) were immersed in 2  degrees C salt
      water. Seven victims were recovered in circulatory arrest with a median
      temperature of 18.4  degrees C (range 15.5-20.2  degrees C). They were all
      rewarmed with extracorporeal membrane oxygenation (ECMO) and were subsequently
      evaluated with advanced neuroradiological and functional testing. The remaining 7
      had established spontaneous circulation without the use of ECMO. One victim
      drowned in the accident. RESULTS: The victims that survived the accident without
      circulatory arrest were predominantly females with a higher body mass index.
      Victims with circulatory arrest pH on arrival was a median of 6.61 (range 6.43
      6.94), with ECMO being established a median of 226 (178-241)min after the
      accident. Magnetic resonance spectroscopy showed neuronal dysfunction in five. In
      five victims initial normal white matter spectra progressed to show evidence of
      abnormal axonal membranes. Based on the seven-level Functional Independence
      Measure test functional outcome was good in six circulatory arrest victims and in
      all without circulatory arrest. Mild to moderate cognitive dysfunction was seen
      in six and severe dysfunction in one circulatory arrest victim. CONCLUSION: Seven
      patients with profound accidental hypothermic circulatory arrest were
      successfully resuscitated using a management approach that included
      extracorporeal rewarming, followed by successive periods of therapeutic
      hypothermia and sedated normothermia and intensive neurorehabilitation. Seven
      other hypothermic victims (core temperature as low as 23  degrees C) that did not
      suffer circulatory arrest also survived the accident.

PMID- 22634432
TI  - Hyperfibrinolysis in out of hospital cardiac arrest is associated with markers of
      hypoperfusion.
AB  - AIM OF THE STUDY: This study investigated the incidence of hyperfibrinolysis upon
      emergency department (ED) admission in patients with out of hospital cardiac
      arrest (OHCA), and the association of the degree of hyperfibrinolysis with
      markers of hypoperfusion. METHODS: From 30 OHCA patients, cardiopulmonary
      resuscitation (CPR) time, pH, base excess (BE), and serum lactate were measured
      upon ED admission. A 20% decrease of rotational thromboelastometry maximum clot
      firmness (MCF) was defined as hyperfibrinolysis. Lysis parameters included
      maximum lysis (ML), lysis onset time (LOT) and lysis index at 30 and 45 min
      (LI30/LI45). The study was approved by the Human Subjects Committee. RESULTS:
      Hyperfibrinolysis was present in 53% of patients. Patients with hyperfibrinolysis
      had longer median CPR times (36 (15-55) vs. 10 (7-18)min; P=0.001), a prolonged
      activated partial thromboplastin time (54 +/- 16 vs. 38 +/- 10s; P=0.006) and
      elevated D-dimers (6.1 +/- 2.1 vs. 2.3 +/- 2.0 MUg/ml; P=0.02) when compared to
      patients without hyperfibrinolysis. Hypoperfusion markers, including pH (6.96 +/-
      0.11 vs. 7.17 +/- 0.15; P<0.001), base excess (-20.01 +/- 3.53 vs. -11.91 +/-
      6.44; P<0.001) and lactate (13.1 +/- 3.7 vs. 8.0 +/- 3.7 mmol/l) were more
      disturbed in patients with hyperfibrinolysis than in non-hyperfibrinolytic
      subjects, respectively. The LOT showed a good association with CPR time (r=-0.76;
      P=0.003) and lactate (r=-0.68; P=0.01), and was longer in survivors (3222 +/-
      34s) than in non-survivors (1,356 +/- 833; P=0.044). CONCLUSION: A substantial
      part of OHCA patients develop hyperfibrinolysis in association with markers for
      hypoperfusion. Our data further suggest that the time to the onset of clot lysis
      may be an important marker for the severity of hyperfibrinolysis and patient
      outcome.

PMID- 22634433
TI  - Ability of code leaders to recall CPR quality errors during the resuscitation of
      older children and adolescents.
AB  - AIM: Performance of high quality CPR is associated with improved resuscitation
      outcomes. This study investigates code leader ability to recall CPR error during
      post-event interviews when CPR recording/audiovisual feedback-enabled
      defibrillators are deployed. PATIENTS AND METHODS: Physician code leaders were
      interviewed within 24h of 44 in-hospital pediatric cardiac arrests to assess
      their ability to recall if CPR error occurred during the event. Actual CPR
      quality was assessed using quantitative recording/feedback-enabled
      defibrillators. CPR error was defined as an overall average event chest
      compression (CC) rate <95/min, depth < 38 mm, ventilation rate >10/min, or any
      interruptions in CPR >10s. We hypothesized that code leaders would recall error
      when it actually occurred >= 75% of the time when assisted by audiovisual alerts
      from a CPR recording feedback-enabled defibrillators (analysis by chi(2)).
      RESULTS: 810 min from 44 cardiac arrest events yielded 40 complete data sets
      (actual and interview); ventilation data was available in 24. Actual CPR error
      was present in 3/40 events for rate, 4/40 for depth, 32/40 for interruptions
      >10s, and 17/24 for ventilation frequency. In post-event interviews, code leaders
      recalled these errors in 0/3 (0%) for rate, 0/4 (0%) for depth, and 19/32 (59%)
      for interruptions >10s. Code leaders recalled these CPR quality errors less than
      75% of the time for rate (p=0.06), for depth (p<0.01), and for CPR interruption
      (p=0.04). Quantification of errors not recalled: missed rate error median=94
      CC/min (IQR 93-95), missed depth error median=36 mm (IQR 35.5-36.5), missed CPR
      interruption >10s median=18s (IQR 14.4-28.9). Code leaders did recall the
      presence of excessive ventilation in 16/17 (94%) of events (p=0.07). CONCLUSION:
      Despite assistance by CPR recording/feedback-enabled defibrillators, pediatric
      code leaders fail to recall important CPR quality errors for CC rate, depth, and
      interruptions during post-cardiac arrest interviews.

PMID- 22634434
TI  - Left ventricular diastolic dysfunction during acute myocardial infarction: effect
      of mild hypothermia.
AB  - BACKGROUND: Mild hypothermia (MH) decreases infarct size and mortality in
      experimental reperfused myocardial infarction, but may potentiate ischaemia
      induced left ventricular (LV) diastolic dysfunction. METHODS: In anaesthetized
      pigs (70 +/- 2 kg), polystyrol microspheres (45 MUm) were infused repeatedly into
      the left circumflex artery until cardiac power output decreased >40%. Then, pigs
      were assigned to normothermia (NT, 38.0 degrees C, n=8) or MH (33.0 degrees C,
      n=8, intravascular cooling) and followed for 6h (CME 6h). p<0.05 vs baseline,
      ?p<0.05 vs NT. RESULTS: In NT, cardiac output (CO) decreased from 6.2 +/- 0.3 to
      3.4 +/- 0.2 l/min, and heart rate increased from 89 +/- 4 to 101 +/- 6 bpm. LV
      end-diastolic volume fell from 139 +/- 8 to 64 +/- 4 ml, while LV ejection
      fraction remained constant (49 +/- 1 vs 53 +/- 4%). The corresponding end
      diastolic pressure-volume relationship was progressively shifted leftwards,
      reflecting severe LV diastolic dysfunction. In MH, CO fell to a similar degree.
      Spontaneous bradycardia compensated for slowed LV relaxation, and the leftward
      shift of the end-diastolic pressure-volume relationship was less pronounced
      during MH. MH increased systemic vascular resistance, such that mean aortic
      pressure remained higher in MH vs NT (69 +/- 2? vs 54 +/- 4 mm Hg). Mixed venous
      oxygen saturation at CME 6h was higher in MH than in NT (59 +/- 4? vs 42 +/- 2%)
      due to lowered systemic oxygen demand during cooling. CONCLUSION: We conclude
      that (i) an acute loss of end-diastolic LV compliance is a major component of
      acute cardiac pump failure during experimental myocardial infarction, and that
      (ii) MH does not potentiate this diastolic LV failure, but stabilizes
      haemodynamics and improves systemic oxygen supply/demand imbalance by reducing
      demand.

PMID- 22634436
TI  - Therapeutic vaccines against HIV infection.
AB  - Resistance to medication, adverse effects in the medium-to-long-term and cost all
      place important limitations on lifelong adherence to combined antiretroviral
      therapy (cART). In this context, new therapeutic alternatives to 'cART for life'
      in HIV-infected patients merit investigation. Some data suggest that strong T
      cell-mediated immunity to HIV can indeed limit virus replication and protect
      against CD4 depletion and disease progression. The combination of cART with
      immune therapy to restore and/or boost immune-specific responses to HIV has been
      proposed, the ultimate aim being to achieve a 'functional cure'. In this
      scenario, new, induced, HIV-specific immune responses would be able to control
      viral replication to undetectable levels, mimicking the situation of the minority
      of patients who control viral replication without treatment and do not progress
      to AIDS. Classical approaches such as whole inactivated virus or recombinant
      protein initially proved useful as therapeutic vaccines. Overall, however, the
      ability of these early vaccines to increase HIV-specific responses was very
      limited and study results were discouraging, as no consistent immunogenicity was
      demonstrated and there was no clear impact on viral load. Recent years have seen
      the development of new approaches based on more innovative vectors such as DNA,
      recombinant virus or dendritic cells. Most clinical trials of these new vectors
      have demonstrated their ability to induce HIV-specific immune responses, although
      they show very limited efficacy in terms of controlling viral replication.
      However, some preliminary results suggest that dendritic cell-based vaccines are
      the most promising candidates. To improve the effectiveness of these vaccines, a
      better understanding of the mechanisms of protection, virological control and
      immune deterioration is required; without this knowledge, an efficacious
      therapeutic vaccine will remain elusive.

PMID- 22634437
TI  - Tolerability and immunogenicity of an inactivated enterovirus 71 vaccine in
      Chinese healthy adults and children: an open label, phase 1 clinical trial.
AB  - In this open labeled phase 1 clinical trial with enterovirus 71 (EV71) vaccine
      (ClinicalTrials.gov number: NCT01267903) performed in Donghai County, Jiangsu
      Province, China, in January 2011. A total of 100 healthy participants, stratified
      by age (40 adults aged 16-22 y and 60 children aged 6-15 y), were enrolled from
      volunteers and sequentially received EV71 vaccines of 160U (only for children),
      320U, or 640U on day 0 and 28, in a manner of dose escalation. All the
      participants were followed for 28 d after each shot. During the study period, 37
      participants reported at least one injection-site or systemic adverse reaction.
      No case of grade 3 adverse reaction or serious adverse event (SAE) was observed.
      Also no dose-related increase in reaction rate was noticed. Pain at injection
      site and fever were the most frequently reported local and systematic reaction,
      respectively. The studied EV71 vaccines demonstrated acceptable tolerability and
      no anti-nuclear antibody (ANA) seropositive was detected pre or post vaccinations
      in participants. Also, no clinically significant abnormal change for the liver or
      kidney function indexes was found. In the according-to-protocol cohort for
      immunogenicity, it was observed one dose of EV71 vaccine elicited good immune
      response in the participants, especially for the ones with sero-positive
      baseline. No obvious dose-response relationship for immunogenicity was found.

PMID- 22634438
TI  - Meningococcal polysaccharide vaccine failure in a patient with C7 deficiency and
      a decreased anti-capsular antibody response.
AB  - A 20-y-old male presented with symptoms of meningococcal sepsis and died despite
      appropriate medical interventions. Blood cultures grew N. meningitidis serogroup
      Y. The patient had received the meningococcal quadrivalent (A,C,W-135,Y)
      polysaccharide vaccine 15 mo previously. Because the patient had a history of
      meningococcal meningitis at age 10, archived serum was obtained for further
      analysis. Complement component C7 was found to be deficient, and antibody levels
      to meningococcal polysaccharides were undetectable for two serogroups and low for
      the infecting serogroup 10 mo post-vaccination. This case highlights the fact
      that some individuals with terminal complement component deficiencies mount an
      impaired or short-lived response to vaccination with meningococcal capsular
      polysaccharides, and underscores the appropriateness of a more aggressive
      vaccination strategy in this patient population.

PMID- 22634439
TI  - Influenza vaccine: an effective preventive vaccine for developing countries.
AB  - The Influenza virus A, B and C causes disease in humans, birds and animals. The
      Influenza type A causes moderate to severe illness in all age groups in humans
      while the illness caused by type B is of milder and it is primarily affects
      children. Among many subtypes of influenza A viruses, currently influenza A(H1N1)
      and A(H3N2) subtypes are circulating among humans. Influenza is a serious public
      health problem that causes severe illnesses and deaths for higher risk
      populations. Influenza virus is characterized by frequent mutations - antigenic
      drifts (minor antigenic change, both A and B) and antigenic shifts (major
      antigenic change, only A). The current human pandemic A/H1N1 is an example of
      antigenic shift. It slowly established circulation globally; subsequently
      endemic/seasonal viruses in both hemi-spheres are H3N2 and H1N1. The novel
      Influenza A (H1N1) 2009 virus was first identified by United State Centers for
      Disease Control and Prevention (US CDC) on 17th April, 2009 in samples from two
      Californian children. As of August 2010, 18,000 people had died globally due to
      the pandemic flu. The illness rates were highest in children and young adults (20
      40% of the population), the hospitalization rates highest in children below the
      age of one. The case fatality rates varied tremendously and were estimated to be
      between 0.0004- 1.5% (0.05% in US, 0.025% in UK, lowest in children). The most
      effective way to prevent the disease or severe outcomes from the illness is
      vaccination. The Trivalent Inactivated vaccines (TIV) are of three types: whole
      virus, split-product, subunit surface-antigen formulations and they are grown in
      embryonated hen's eggs. Whole-virus vaccines, because of adverse reactions,
      especially in children, are not currently used. Most influenza vaccines are split
      product vaccines, produced from detergent treated, highly purified influenza
      virus, or surface-antigen vaccines containing purified hemagglutinin and
      neuraminidase.

PMID- 22634441
TI  - Parental views on vaccine safety and future vaccinations of children who
      experienced an adverse event following routine or seasonal influenza vaccination
      in 2010.
AB  - To assess parental vaccine safety views and future vaccination decisions after an
      adverse event following immunization (AEFI) experienced by their child. A cross
      sectional telephone survey was conducted of parents of children aged 0-7 y,
      identified in AEFI reports submitted to the South Australian Immunization
      Section, Department Health. The reports included childhood National Immunization
      Program (NIP), seasonal or pandemic influenza vaccines. Interviews were conducted
      following a national suspension of the 2010 seasonal trivalent influenza (STIV)
      vaccine. Parental attitudes toward vaccine safety, reasons for reporting the AEFI
      and impact on future vaccination intent were assessed. Of 179 parents
      interviewed, 88% were confident in the safety of vaccines in general. Parents
      reporting an AEFI to the STIV were more likely to state the event had influenced
      future vaccination decisions than the NIP vaccine reporters (65% vs 14%, p <
      0.001), with 63% stating refusal or hesitance to re-vaccinate their children
      against influenza. Media reports of the 2010 STIV program suspension was the most
      common reason for reporting an AEFI for parents of children who received an
      influenza vaccination. The AEFI experience did not impact on parental decision to
      continue with routine childhood NIP schedules, regardless of whether children
      received influenza or NIP vaccines. In contrast, most parents whose child
      experienced an AEFI to the 2010 STIV stated decreased confidence in the safety of
      influenza vaccines, which is likely to have impacted on the uptake of seasonal
      influenza vaccination in 2011. Addressing influenza vaccine safety concerns to
      promote influenza vaccination in the community is required.

PMID- 22634440
TI  - The human potential of a recombinant pandemic influenza vaccine produced in
      tobacco plants.
AB  - Rapid production of influenza vaccine antigen is an important challenge when a
      new pandemic occurs. Production of recombinant antigens in plants is a quick,
      cost effective and up scalable new strategy for influenza vaccine production. In
      this study, we have characterized a recombinant influenza haemagglutinin antigen
      (HAC1) that was derived from the 2009 pandemic H1N1 (pdmH1N1) virus and expressed
      in tobacco plants. Volunteers vaccinated with the 2009 pdmH1N1 oil-in-water
      adjuvanted vaccine provided serum and lymphocyte samples that were used to study
      the immunogenic properties of the HAC1 antigen in vitro. By 7 d post vaccination,
      the vaccine fulfilled the licensing criteria for antibody responses to the HA
      detected by haemagglutination inhibition and single radial hemolysis. By ELISA
      and ELISPOT analysis we showed that HAC1 was recognized by specific serum
      antibodies and antibody secreting cells, respectively. We conducted a kinetic
      analysis and found a peak of serum HAC1 specific antibody response between day 14
      and 21 post vaccination by ELISA. We also detected elevated production of IL-2
      and IFNgamma and low frequencies of CD4(+) T cells producing single or multiple
      Th1 cytokines after stimulating PBMCs (peripheral blood mononuclear cells) with
      the HAC1 antigen in vitro. This indicates that the antigen can interact with T
      cells, although confirming an effective adjuvant would be required to improve the
      T-cell stimulation of plant based vaccines. We conclude that the tobacco derived
      recombinant HAC1 antigen is a promising vaccine candidate recognized by both B-
      and T cells.

PMID- 22634442
TI  - Clinical effectiveness of 23-valent pneumococcal polysaccharide vaccine against
      pneumonia in patients with chronic pulmonary diseases: a matched case-control
      study.
AB  - BACKGROUND: The effectiveness of the 23-valent polysaccharide pneumococcal
      vaccine (PPV-23) is controversial, especially among people with high-risk
      conditions. This study assessed the clinical effectiveness of vaccination against
      pneumonia among patients with chronic pulmonary diseases. METHODS: We conducted a
      population-based case-control study including 96 non-immunocompromised patients
      with clinical diagnosis of chronic pulmonary disease (chronic bronchitis,
      emphysema and/or asthma), aged 50 y or older, with radiographically confirmed
      pneumococcal pneumonia (19 bacteremic and 77 nonbacteremic cases) and 192
      outpatient control subjects with similar chronic pulmonary diseases (matched by
      primary care center, age, sex and main comorbidity). Adjusted odds ratios (ORs)
      for vaccination were calculated using conditional logistic regression,
      controlling for by underlying conditions. RESULTS: Pneumococcal vaccination did
      not alter significantly the risk of overall pneumococcal pneumonia [adjusted OR:
      0.71; 95% confidence interval (CI): 0.37-1.39]. Point estimates of vaccine
      effectiveness was the maximum against bacteremic pneumococcal pneumonia due to
      vaccine-serotypes, although neither reached statistical significance (adjusted
      OR: 0.51; 95% CI: 0.03-8.19). Vaccination pointed to a smaller benefit against
      nonbacteremic pneumococcal pneumonia (adjusted OR: 0.66; 95% CI: 0.33-1.34).
      Pneumococcal vaccination was associated with a non-statistically significant
      reduction in the risk of all pneumococcal pneumonia among persons 75 y or older
      (adjusted OR: 0.45; 95% CI: 0.16-1.27), but no apparent protective effect emerged
      among people 50-74 y (adjusted OR: 1.48; 95% CI: 0.62-3.56). CONCLUSIONS: The
      effectiveness of the PPV-23 in preventing pneumonia among patients with chronic
      pulmonary disease is uncertain. Our results point to PPV-23 having little or null
      effect against pneumococcal pneumonia in such patients, but definitive
      conclusions cannot be established based on our data.

PMID- 22634443
TI  - Background morbidity in HIV vaccine trial participants from various geographic
      regions as assessed by unsolicited adverse events.
AB  - BACKGROUND: Recently, more clinical trials are being conducted in Africa and
      Asia, therefore, background morbidity in the respective populations is of
      interest. Between 2000 and 2007, the International AIDS Vaccine Initiative
      sponsored 19 Phase 1 or 2A preventive HIV vaccine trials in the US, Europe, Sub
      Saharan Africa and India, enrolling 900 healthy HIV-1 uninfected volunteers.
      OBJECTIVE: To assess background morbidity as reflected by unsolicited adverse
      events (AEs), unrelated to study vaccine, reported in clinical trials from four
      continents. METHODS: All but three clinical trials were double-blind, randomized,
      and placebo-controlled. Study procedures and data collection methods were
      standardized. The frequency and severity of AEs reported during the first year of
      the trials were analyzed. To avoid confounding by vaccine-related events,
      solicited reactogenicity and other AEs occurring within 28 d after any
      vaccination were excluded. RESULTS: In total, 2134 AEs were reported by 76% of
      all participants; 73% of all events were mild. The rate of AEs did not differ
      between placebo and vaccine recipients. Overall, the percentage of participants
      with any AE was higher in Africa (83%) compared with Europe (71%), US (74%) and
      India (65%), while the percentage of participants with AEs of moderate or greater
      severity was similar in all regions except India. In all regions, the most
      frequently reported AEs were infectious diseases, followed by gastrointestinal
      disorders. CONCLUSIONS: Despite some regional differences, in these healthy
      participants selected for low risk of HIV infection, background morbidity posed
      no obstacle to clinical trial conduct and interpretation. Data from controlled
      clinical trials of preventive interventions can offer valuable insights into the
      health of the eligible population.

PMID- 22634444
TI  - Incidence of adverse events in premature children following 2-month vaccination.
AB  - Using a population based self-controlled case series study design we examined
      data on 834,740 children in the province of Ontario, Canada. We observed that
      when comparing to SGA10 term children (term children born in the lowest 10th
      percentile of weight for a given gestational age), relative incidence of
      emergency room visits and admission in the 3 d post 2 mo vaccination
      progressively decreased in near term (relative incidence ratio 0.89 (95% CI 0.74
      1.07)) and very premature children [(0.67(0.49-0.93)]. When compared with all
      term children this decrease in risk is not statistically significant. We
      speculate that the immune response is reduced in premature children resulting in
      reduced adverse events. This is masked when comparing to all term children
      because the reduced birth weight of premature children results in a comparatively
      increased dose of vaccine. This in turn results in an increased immune response
      and risk of immediate adverse reactions. Future studies of immune response in
      premature children should examine the impact of weight at the time of
      immunization.

PMID- 22634445
TI  - Designing around patents with an immunotherapy case: a take-home message of a
      full court decision by the US Federal Circuit.
AB  - In TiVo Inc. V. EchoStar Corp case (2010), all judges of the US Court of Appeals
      for the Federal Circuit (CAFC) reemphasized that legitimate design around a
      competitor's patents is always encouraged as a route of innovation. The modified
      elements of the design-around must be evaluated against the asserted claim(s) to
      ensure that each limitation is met before concluding that the modification is not
      substantially different from the previously adjudged infringed product. Regarding
      the significance of the differences between the features adjudged as infringement
      and the modified characteristics of the newly designed products, CAFC stated that
      the determination may refer to the rule of obviousness. In this article, we
      present an immunotherapy case that shows how to overcome an obviousness rejection
      by showing an unexpected result. The new design using an anti-VEGF antibody
      encoding sequence in vaccinia virus should significantly increase its therapeutic
      effect. Furthermore, the newly-designed virus would provide tumor-localized
      delivery of the antibody and enhance anti-tumor activity.

PMID- 22634446
TI  - A randomized trial of immunotherapy for persistent genital warts.
AB  - AIM: To determine whether immunotherapy with HPV6 L1 virus like particles (VLPs)
      without adjuvant (VLP immunotherapy) reduces recurrence of genital warts
      following destructive therapy. TRIAL DESIGN: A randomized placebo controlled
      blinded study of treatment of recurrent genital warts amenable to destructive
      therapy, conducted independently in Australia and China. METHODS: Patients
      received conventional destructive therapy of all evident warts together with
      intramuscular administration of 1 ug, 5 ug or 25 ug of VLP immunotherapy, or of
      placebo immunotherapy (0.9% NaCl), as immunotherapy at week 0 and week 4. Primary
      outcome, assessed at week 8, was recurrence of visible warts. RESULTS: Of 33
      protocol compliant Brisbane recipients of placebo immunotherapy, 11 were disease
      free at two months, and a further 9 demonstrated reduction of > 50% in total wart
      area. Wart area reduction following destructive treatment correlated with prior
      duration of disease. Among 102 protocol compliant Brisbane recipients of VLP
      immunotherapy, disease reduction was significantly greater than among the placebo
      immunotherapy (50% +/- s.e.m. 7%) recipients for subjects receiving 5 ug or 25 ug
      of VLP immunotherapy/dose (71% +/- s.e.m. 7%) but not for those receiving 1 ug
      VLP immunotherapy/dose (42% +/- 7%). Of 52 protocol compliant placebo
      immunotherapy recipients in Wenzhou, 37 were disease free at two months, and a
      further 8 had > 50% disease reduction. Prior disease duration was much shorter in
      Wenzhou subject (8.1 +/- 1.1 mo) than in Brisbane subjects (53.7 +/- 5.5 mo). No
      significant reduction in mean wart area was observed for the 168 Wenzhou protocol
      compliant subjects who also received VLP immunotherapy. CONCLUSIONS: This study
      confirms the findings in a previous open label trial that administration of VLP
      immunotherapy may assist in clearance of recurrent genital warts in patients for
      whom destructive therapy is unsuccessful and that unsuccessful destructive
      therapy is more common with increasing prior disease duration.

PMID- 22634447
TI  - Low response to a monovalent inactivated unadjuvanted influenza A (H1N1) pdm09
      vaccine in pediatricians of a general hospital in Japan.
AB  - Immunization of health care personnel (HCP) is critically important to reduce
      healthcare-associated influenza infections substantially. During 2009-2010, 74%
      of all HCP at Kitano Hospital, Osaka, Japan, including 94% of pediatricians,
      received the monovalent unadjuvanted influenza A (H1N1) pdm09 vaccine. We
      evaluated the vaccine's immunogenicity. Sixteen pediatricians received 15 MUg
      hemagglutinin antigen subcutaneously. Antibody titer assays were conducted using
      hemagglutination-inhibition antibody assay on days 0 and 21, and at 5 mo after
      vaccination. Seroprotection rates, seroconversion rates, and geometric mean titer
      folds at 21 d were, respectively, 43.8%, 43.8%, and 5.4 in all subjects, 70.0%,
      70.0%, and 8.0 in subjects aged 27-34 y, and 0.0%, 0.0%, and 8.0 in subjects aged
      >= 35 y. None of the latter group met the European Medicines Agency criteria. We
      hope to adopt intradermal routes and further the development of the influenza
      vaccine using new technology to improve immunogenicity in Japan.

PMID- 22634448
TI  - Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal non
      typeable Hemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co
      administered with the DTPw-HBV/Hib vaccine in Indian infants: a single-blind,
      randomized, controlled study.
AB  - In India, pneumococcal diseases are major causes of child mortality, and
      effective vaccines against Streptococcus pneumoniae are needed. This single
      blind, randomized study assessed the immunogenicity, reactogenicity, and safety
      of the 10-valent pneumococcal non-typeable Hemophilus influenzae (NTHi) protein D
      conjugate vaccine (PHiD-CV) co-administered with DTPw-HBV/Hib in Indian infants
      as 3-dose primary vaccination course. A total of 360 infants were randomized
      (2:1) to receive either PHiD-CV co-administered with DTPw-HBV/Hib (PHiD-CV group)
      or a Hib vaccine co-administered with DTPw-HBV (control group) at 6, 10, and 14
      weeks of age. For each vaccine pneumococcal serotype, the percentage of infants
      in the PHiD-CV group with antibody concentrations >= 0.2 ug/mL one month after
      the third vaccine dose was at least 98.3%, except for serotypes 6B (77.7%) and
      23F (89.5%), and opsonophagocytic activity titers >= 8 were measured in at least
      95.7% of infants, except for serotypes 1 (90.5%) and 6B (84.5%). In addition, all
      the infants in the PHiD-CV group were seroprotected against diphtheria, tetanus,
      Hib, and hepatitis B or seropositive for antibodies against pertussis and NTHi
      protein D (except one infant). Incidences of solicited local and general symptoms
      were comparable between groups, except for fever (axillary temperature >= 37.5
      degrees C), which seemed to occur more frequently in the PHiD-CV group. In
      conclusion, PHiD-CV was shown to be immunogenic and well-tolerated when co
      administered with DTPw-HBV/Hib in Indian infants.

PMID- 22634449
TI  - Social support of low-income Brazilian mothers related to time to completion of
      childhood vaccinations.
AB  - Our study objective was to examine how maternal social support and depressive
      symptoms are associated with time to completion of childhood vaccinations. We
      used cross-sectional data from 582 randomly-selected, low-income Brazilian
      children. Adjusted Cox Proportional Hazard models were used to estimate time to
      completing the first three recommended oral polio and diphtheria, pertussis and
      tetanus (DPT) vaccinations as well as their booster doses. Among only the women
      with low social support, each ten-point increase on the Medical Outcomes Study -
      Social Support Scale was associated with a 20% increased chance of completing the
      first three recommended vaccinations for polio and DPT at any given time (HR =
      1.20, 95% CI 1.02-1.42). Although falling short of statistical significance, also
      among mothers with low social support, we found a suggestive finding of increased
      social support associated with 25% greater chance of completing polio and DPT
      booster vaccines at any given time (HR = 1.25, 95% CI 0.98-1.60). There was no
      association between maternal depressive symptoms and vaccination completion.
      Among mothers with little social support, increased social support may be
      important for timely completion of vaccinations in low-income Brazilian children.
      Longitudinal studies and research on mechanisms explaining associations between
      maternal social support and childhood vaccination are needed.

PMID- 22634450
TI  - Titering of 2009 pandemic H1N1 influenza virus hemagglutinin inhibition antibody
      in nonvaccinated pregnant women in Shiraz, Southern Iran.
AB  - Influenza may cause severe complications for pregnant women. In this study
      antibody response against 2009 H1N1 influenza virus in pregnant women was
      investigated. This seroprevalance cross sectional and questionnaire based study
      was conducted using a convenient sampling method. Blood samples of pregnant women
      were checked for antibodies against 2009 H1N1 influenza virus using
      hemagglutination inhibition assay. An antibody titer level of >= 1:40 dilution
      was considered as the protective level. 167 (43.60%) of 383 pregnant women who
      participated in this study had protective antibody levels against this virus. 62
      (35.63%) of 3rd trimester, 79 (46.74%) of 2nd trimester, and 21(52.50%) of 1st
      trimester pregnant women were immune respectively (chi2(for trend) = 8.20, p <
      0.004). Lack of protective antibody level was significantly seen more in pregnant
      women of 3rd trimester of pregnancy (OR = 2.37, CI = 1.09-5.18). Pregnant women
      with higher education (OR = 1.67, CI = 1.02-2.73) and those with history of
      anemia (OR = 2.09, CI = 1.18-3.68) had more immunity. Older women (OR = 0.95, CI
      = 0.91-0.99) and those with history of psychological diseases (OR = 0.19, CI =
      0.05-0.70) had less immunity. Vaccination of pregnant women, especially those who
      are in the higher trimesters of pregnancy, older, or less educated, against the
      2009 H1N1 influenza virus should be continued.

PMID- 22634451
TI  - Vaccination against viral hepatitis of HIV-1 infected patients.
AB  - Reciprocal interactions between HIV and HAV or HBV can increase risk of morbidity
      and mortality in HIV disease and/or worsened the natural course of the hepatitis
      viruses. Hepatitis A vaccination is recommended for HIV infected patients at risk
      for exposure or severe disease: men who have sex with men, injecting drug users,
      patients with chronic liver disease and patients traveling in high endemic
      countries. As for healthy adults the scheme of vaccination is two doses 6 or 12
      mo apart, nevertheless, seroconversion rates are lower. A third dose could
      improve the seroconversion rates. Hepatitis B vaccination is recommended for all
      HIV infected persons lacking prior immunity. As the immune response to hepatitis
      B vaccines is impaired in HIV-infected adults, four double doses of hepatitis B
      vaccine could enhance serological response. To assume a higher immune response,
      vaccines should be administered in HIV-infected patients with undetectable HIV
      viral load and high CD4 cell count.

PMID- 22634452
TI  - Cholera vaccine: new preventive tool for endemic countries.
AB  - Cholera is a major global public health problem and remains an important threat
      in almost every developing country, especially in areas where population
      overcrowding and poor sanitation are common, such as slums and refugee camps.
      Cholera is one of the most dreaded diseases in the world, in some cases leading
      to death within 24 h if left untreated. Without treatment, severe infection has a
      mortality rate of 30-50%. In 2007, WHO recorded 177,963 cholera cases and 4,031
      deaths worldwide. However, the estimated actual burden of cholera is in the
      vicinity of 3 to 5 million cases and 100,000 to 130,000 deaths per year. The
      disease is endemic to parts of Africa, Asia, the Middle East and South America.
      Large outbreaks are common after natural disasters or in populations displaced by
      war, where there is inadequate sewage disposal and contaminated water. In India,
      during the 10-y period (1997-2006) studied, the states having the highest number
      of reported outbreaks were West Bengal, Orissa, Maharashtra and Kerala, which
      together accounted for 60% of all reported outbreaks. A review of cholera cases
      in India reported to WHO from 2003-2007 showed that the numbers were in the few
      thousands with a case fatality rate of < 1%. However, it is believed that the
      number of cholera cases and deaths occurring annually in India is much greater
      than the number reported. A literature review covering a four-year period from
      2003 to 2006 found reported cholera outbreaks in 18 of the 35 States and Union
      Territories of India. Of these, 11 had cholera outbreaks reported for multiple
      years. Vietnam has produced a cheaper variant of killed whole-cell vaccine devoid
      of the B subunit. This vaccine contains both Vibrio cholerae O1 and O139, and
      provides 50 per cent protection for at least three years after vaccination. For
      endemic cholera, population-level immunity is relatively high, making control
      possible with relatively low vaccine coverage levels. This vaccine should be used
      in areas where cholera is endemic, particularly in those at risk of outbreaks, in
      conjunction with other prevention and control strategies.

PMID- 22634453
TI  - Prospects in boron neutron capture therapy of brain tumors.

PMID- 22634454
TI  - The Association for Surgical Education's roadmap for research on surgical
      simulation.

PMID- 22634455
TI  - Percutaneous retrogasserian balloon compression for trigeminal neuralgia.

PMID- 22634456
TI  - Safety of closed brain biopsy: population-based studies weigh in.

PMID- 22634457
TI  - We can control the tumor but can we stop the pain?

PMID- 22634458
TI  - Surgery versus embolization in spinal dural arteriovenous fistulas: the ideal
      competition to improve the care of patients.

PMID- 22634459
TI  - Seeing the forest for the trees.

PMID- 22634460
TI  - Brain metastasis management: deciding when less is more.

PMID- 22634461
TI  - Efficacy of surgical treatment for lumbar stenosis with the X-STOP: an issue in
      need of closer inspection.

PMID- 22634462
TI  - Cavernous malformations.

PMID- 22634463
TI  - Do meningioma patients benefit from antiepileptic drug treatment?

PMID- 22634465
TI  - Pituitary metastases: what is the role of surgery?

PMID- 22634464
TI  - Nervus intermedius and geniculate neuralgia.

PMID- 22634466
TI  - Re-engineering the subthalamus.

PMID- 22634467
TI  - Treatment of ruptured middle cerebral aneurysms associated with intracerebral
      hematomas.

PMID- 22634468
TI  - Nervus intermedius.

PMID- 22634469
TI  - External cervical orthosis (ECO): to have or not to have.

PMID- 22634470
TI  - Odorant receptor co-receptor Orco is upregulated by methyl eugenol in male
      Bactrocera dorsalis (Diptera: Tephritidae).
AB  - Bactrocera dorsalis is a destructive fruit-eating pest that causes severe
      economic damage to the fruit and vegetable industry. Methyl eugenol (ME) has been
      widely used as an effective sexual attractant for male fruit flies through
      olfactory perception. However, the molecular mechanism underlying the olfactory
      perception of ME remains unknown. Here, we report the characterization and
      functional analysis of a newly discovered cDNA that encodes a Drosophila
      melanogaster odorant receptor co-receptor Orco ortholog in B. dorsalis. qRT-PCR
      analysis revealed that it was abundantly expressed in the antenna of adult B.
      dorsalis. Notably, Orco was upregulated by ME in the antenna of male flies.
      Mature males of B. dorsalis showed significant taxis toward ME within 0.5h, and
      Orco was significantly upregulated in the attracted adults within the same
      period. Silencing Orco through the ingestion of dsRNA reduced the attractive
      effects of ME. These data suggest that Orco may play an essential role in ME
      attraction in the olfactory signal transduction pathway.

PMID- 22634471
TI  - Is myocutaneous flap alone sufficient for reconstruction of chest wall
      osteoradionecrosis?
AB  - OBJECTIVES: This study was carried out to determine whether the myocutaneous
      flap, alone, is sufficient to reconstruct a chest wall defect after
      osteoradionecrosis and provide satisfactory stability to the chest wall. METHODS:
      This study involved five patients who were subjected to post-mastectomy
      radiotherapy as a treatment for breast cancer. Excision of the ulcer and all the
      necrotic ribs, with preservation of the parietal pleura and reconstruction with
      the latissimus dorsi flap, was done without the use of either an artificial
      prosthesis or autologous rib to reconstruct the chest wall defect. RESULTS:
      Clinical and radiological follow-up showed no complications regarding respiratory
      impairment or pleural complications. CONCLUSIONS: The use of myocutaneous flap in
      patients with chest wall defect following osteoradionecrosis is satisfactory to
      cover the chest wall defect and provide satisfactory stability to the chest wall.

PMID- 22634472
TI  - Is there a suitable method of anticoagulation in pregnant patients with
      mechanical prosthetic heart valves?
AB  - A best evidence topic was written according to a structured protocol in order to
      identify the mode of anticoagulation that has the best safety profile for both
      the mother and the foetus in pregnant patients with mechanical prosthetic heart
      valves. A total of 281 papers were identified using the reported search, of which
      eight represented the best evidence to answer the clinical question. The authors,
      date, journal, study type, population, main outcome measures and results are
      tabulated. The reported measures were foetal mortality, maternal mortality,
      congenital abnormalities and embryopathy, and maternal thromboembolic and
      haemorrhagic complications. The medical orthodoxy has warned of the combination
      of oral anticoagulation and pregnancy due to the well-documented warfarin
      embryopathy. Yet only one of the reported papers identified a greater incidence
      of foetal aberrations among warfarin use, with the highest reported rate being
      6.4% and two of the assessed papers reporting no embryopathy at all. Foetal
      mortality with oral anticoagulation use ranged from 1.52 to 76%. All reported
      publications demonstrated a superior maternal outcome with warfarin use, with a
      range of thromboembolic events from 0 to 10% in comparison with 4 to 48% where
      heparin was used. Thus, it is concluded that warfarin is a more durable
      anticoagulant with a better maternal outcome despite it carrying a greater foetal
      risk. Although, in contrast to previous teaching, the risks of embryopathy are
      not the major drawback of oral anticoagulation. Heparin is consistently less
      effective, but may be preferred for the superior foetal outcome. Heparin usage
      during the first trimester reduces the foetal risk but is still associated with
      an adverse maternal outcome. While the focus for clinicians looking after
      pregnant women with mechanical heart valves may be to prevent maternal
      thromboembolic complications, the overriding concern for many women is to avoid
      any harm to their unborn child, even when this places their health at risk. Thus
      women with mechanical heart valves must be fully informed of the risks involved
      with different anticoagulation for an informed decision to be made.

PMID- 22634473
TI  - CD44 expression in astrocytes and microglia is associated with ALS progression in
      a mouse model.
AB  - Amyotrophic lateral sclerosis (ALS) is a motor neuron-specific neurodegenerative
      disease. An increasing body of evidence suggests that, in addition to cell
      autonomous regulation, i.e., pathological changes in motor neurons, non-cell
      autonomous mechanisms involving glial cells play critical roles in the
      pathogenesis of ALS. CD44 functions as a receptor for osteopontin and hyaluronan,
      and has been implicated in inflammation associated with neuronal injuries.
      However, this membrane glycoprotein has been poorly studied in ALS. Here we
      investigated its expression during ALS progression using SOD1(G93A) mice. CD44
      expression increased around the onset of disease and then increased continuously.
      Astrocytes and microglia expressed CD44 in vivo. Consistent with these findings,
      primary cultured microglia began to express CD44 upon activation with LPS and
      interferon-gamma. CD44 expression in primary cultured astrocytes was also
      enhanced by activation with interferon-gamma+TNF-alpha or bFGF alone. As CD44 was
      detected in cell lysate, but not in culture media of astrocytes and microglia, it
      was likely that these glial cells expressed a membrane-bound form of CD44. Our
      study demonstrates that CD44 expression in astrocytes and microglia is closely
      associated with the pathogenesis of ALS, and suggests that inflammatory responses
      involving CD44 may play a role in this disease.

PMID- 22634475
TI  - Hipk proteins dually regulate Wnt/Wingless signal transduction.
AB  - The Wnt/Wingless (Wg) pathway is an evolutionarily conserved signaling system
      that is used reiteratively, both spatially and temporally, to control the
      development of multicellular animals. The stability of cytoplasmic beta
      catenin/Armadillo, the transcriptional effector of the pathway, is controlled by
      sequential N-terminal phosphorylation and ubiquitination that targets it for
      proteasome-mediated degradation. Orthologous members of the Homeodomain
      interacting protein kinase family from Drosophila to vertebrates have been
      implicated in the regulation of Wnt/Wingless signaling. In Drosophila, as a
      consequence of Hipk activity, cells accumulate stabilized Armadillo that directs
      the expression of Wg-specific target genes. Hipk promotes the stabilization of
      Armadillo by inhibiting its ubiquitination (and hence subsequent degradation) by
      the SCF(Slimb) E3 ubiquitin ligase complex. Vertebrate Hipk2 impedes beta-catenin
      ubiquitination to promote its stability and the Wnt signal in a mechanism that is
      functionally conserved. Moreover, we describe here that Hipk proteins have a role
      independent of their effect on beta-catenin/Armadillo stability to enhance
      Wnt/Wingless signaling.

PMID- 22634476
TI  - The gender- and fat depot-specific regulation of leptin, resistin and adiponectin
      genes expression by progesterone in rat.
AB  - Progesterone affects lipid metabolism in adipose tissue and influences fat
      distribution in human. The aim of the study was to analyze the effect of
      progesterone on rat body and fat mass and on expression of genes encoding
      adipokines involved in the regulation of energy homeostasis. The results
      presented here indicate that progesterone administration to females caused
      increase in body and inguinal white adipose tissue mass. The increase of inguinal
      white adipose tissue mass is associated with the hypertrophy of adipocyte. The
      same dose of progesterone caused increase of its circulating concentration in
      males, however it barely reached the value observed in non-treated control
      females and did not have any effect on body and fat mass. The elevated
      circulating progesterone concentration was associated with an approximately 6-
      and 2-fold increase of leptin and resistin mRNA level respectively, and 2-fold
      decrease of adiponectin mRNA level only in inguinal white adipose tissue of
      females. RU 486, specific antagonist of progesterone receptor, abolished the
      effect of progesterone on the adipokine mRNA level in inguinal adipose tissue. In
      males, the elevated circulating progesterone concentration showed no effects on
      leptin, resistin or adiponectin mRNA level in inguinal, retroperitoneal or
      epididymal adipose tissue. Moreover, the results presented in this paper
      demonstrate a relatively high level of progesterone receptor mRNA in inguinal
      white adipose tissue of females, which was down-regulated in response to
      progesterone administration. In retroperitoneal adipose tissue of control females
      progesterone receptor mRNA level was approximately 3-fold lower as compared to
      inguinal adipose tissue. In inguinal, epididymal and retroperitoneal white
      adipose tissue of males progesterone receptor mRNA was hardly detected. Our
      results suggest that depot- and sex-dependent responsiveness of adipose tissue to
      the pharmacological dose of progesterone is controlled by both circulating
      concentration of progesterone and the white adipose tissue progesterone receptor
      level.

PMID- 22634478
TI  - Increased cysteinyl leukotriene concentration and receptor expression in
      tonsillar tissues of Chinese children with sleep-disordered breathing.
AB  - BACKGROUND: Evidence suggests that increased leukotriene level and receptor
      protein expression emerged in the adenotonsillar tissue of children with sleep
      disordered breathing (SDB). Nevertheless, few studies have investigated the
      contribution of disease severity in the cysteinyl leukotriene (CysLT) production
      and cysteinyl leukotriene receptor (CysLTR) expression. Furthermore, the
      relationship between local upper-airway and systemic inflammatory responses
      remains undefined. METHODS: A prospective, observational study that included
      standard questionnaires, physical examinations and overnight polysomnography.
      CysLTs were determined from serum, urine and tonsillar homogenate supernatant by
      means of enzyme-linked immunosorbent assays. The protein expressions of CysLTR
      were measured using Western blot analysis. RESULTS: Children with SDB had
      increased intratonsillar CysLT levels as well as CysLT subtype 1 receptor (CysLT1
      R) and CysLT subtype 2 receptor (CysLT2-R) protein expression than the control
      group. CysLT concentration was positively correlated with body mass index z-score
      and apnea-hypopnea index (r=0.454 and 0.487, p<0.001 respectively), and
      negatively correlated with pulse oximetric saturation nadir (r=-0.518, p<0.001).
      Upper-airway intratonsillar CysLT production was positively correlated with
      systemic production (vs. urinary LTE4: r=0.456, p<0.001; vs. serum CysLTs:
      r=0.440, p<0.001). Immunoblots showed that CysLT1-R protein expressions were
      modestly higher in the severe group when compared to the mild group. In contrast,
      there were no differences in CysLT2-R protein appearing among the SDB subgroups.
      CONCLUSIONS: Increased CysLT level and receptor expression in upper-airway
      tonsillar tissues are related to disease severity in SDB children. The local and
      systemic CysLT production were positively correlated.

PMID- 22634477
TI  - Antiestrogenic activity of flavonoid phytochemicals mediated via the c-Jun N
      terminal protein kinase pathway. Cell-type specific regulation of estrogen
      receptor alpha.
AB  - Flavonoid phytochemicals act as both agonists and antagonists of the human
      estrogen receptors (ERs). While a number of these compounds act by directly
      binding to the ER, certain phytochemicals, such as the flavonoid compounds
      chalcone and flavone, elicit antagonistic effects on estrogen signaling
      independent of direct receptor binding. Here we demonstrate both chalcone and
      flavone function as cell type-specific selective ER modulators. In MCF-7 breast
      carcinoma cells chalcone and flavone suppress ERalpha activity through
      stimulation of the stress-activated members of the mitogen-activated protein
      kinase (MAPK) family: c-Jun N-terminal kinase (JNK)1 and JNK2. The use of
      dominant-negative mutants of JNK1 or JNK2 in stable transfected cells established
      that the antiestrogenic effects of chalcone and flavone required intact JNK
      signaling. We further show that constitutive activation of the JNK pathway
      partially suppresses estrogen (E2)-mediated gene expression in breast, but not
      endometrial carcinoma cells. Our results demonstrate a role for stress-activated
      MAPKs in the cell type-specific regulation of ERalpha function.

PMID- 22634479
TI  - In-vivo antioxidant and immunomodulatory activity of mesuol isolated from Mesua
      ferrea L. seed oil.
AB  - Mesua ferrea L. (Nagkesar) is traditionally being used for antiseptic, anti
      inflammatory, antiasthmatic and antiallergic activities. It is an ingredient of
      ayurvedic formulations like Brahma Rasayana and Chyavanprash which are being used
      to improve immunity. The present study was performed to evaluate immunomodulatory
      activity of mesuol isolated from M. ferrea seed oil in experimental animals. In
      humoral immune response model, mesuol evoked a significant dose dependent
      increase in antibody titer values in cyclophosphamide (50 mg/kg, i.p., 9th and
      16th day) induced immunosuppression which was sensitized with sheep red blood
      cells (SRBC) on the 7th and 14th day of experiment. In cellular immune response
      model, an increase in paw volume was recorded on the 23rd day in cyclophosphamide
      induced immunosuppressed rats treated with SRBC (0.03 ml 2% v/v, s.c.) on the
      21st day. Mesuol restored the hematological profile in cyclophosphamide induced
      myelosuppression model. Mesuol potentiated percentage neutrophil adhesion in
      neutrophil adhesion test in rats and phagocytosis in carbon clearance assay. The
      study indicated immunomodulatory activity of mesuol.

PMID- 22634480
TI  - Mechanistic exploration of AhR-mediated host protection against Streptococcus
      pneumoniae infection.
AB  - Streptococcus pneumoniae is a primary cause of invasive bacterial infection and
      pneumonia and is one of the leading causes of death worldwide. In prior studies
      we showed that pre-treating mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD),
      a potent agonist of the aryl hydrocarbon receptor (AhR), protects against S.
      pneumoniae-induced mortality and reduces pulmonary bacterial burden. The current
      studies were conducted to help elucidate the mechanism for this protective
      effect, and to characterize the response in the lung during the first 10h
      following infection. C57Bl/6 mice were treated with TCDD one day prior to
      intranasal infection with serotype 3 S. pneumoniae. Monitoring of bacteria in the
      lung airways revealed that bacterial growth was inhibited in the TCDD-treated
      animals within 10h of infection. To address the mechanism of this rapid
      protective response, macrophages, neutrophils, and invariant Natural Killer T
      (iNKT) cells were quantified, and levels of natural antibodies produced by B-1 B
      cells were evaluated. Functional assays addressed whether AhR activation reduced
      the capacity of lung epithelial cells to bind bacteria, and whether TCDD
      treatment enhanced production of antimicrobial agents in the lung or blood. None
      of the hypothesized mechanisms was able to explain the protective effect.
      Finally, the exposure paradigm was manipulated to test whether administration of
      TCDD after instillation of the bacteria was also protective. Results showed that
      TCDD must be administered in advance of exposure to bacteria, suggesting that the
      lung environment is rendered inhospitable to the pathogens.

PMID- 22634483
TI  - Mitochondria-driven cell elongation mechanism for competing sperms.
AB  - Sexual competition has selected a number of extreme phenotypes like the tail
      ornament of peacock male. Sperm tail of Drosophilidae elongate up to 6 cm as a
      result of evolutionary selection for reproductive fitness among competing sperms.
      Sperm elongation takes place post meiotically and can proceed in the absence of
      an axoneme. Here, we used primary cultures of elongating spermatids of D.
      melanogaster to demonstrate that sperm elongation is driven by interdependent
      extension of giant mitochondria and microtubule array that is formed around the
      mitochondrial surface. This work established that, in addition to functioning as
      an energy source, mitochondria can serve as internal skeleton for shaping cell
      morphology.

PMID- 22634484
TI  - Optical superresolution and visual hyperacuity.
AB  - Classically, diffraction theory sets a boundary for the resolving capacity of
      optical instruments. Yet some visual thresholds have values much better than the
      traditional resolution limit. Recent developments in superresolution, an area of
      optical physics and engineering with claims of transcending the stated resolution
      limits of optical instruments, are reviewed and their possible relevance to
      visual spatial processing and to the exploration of the eye's structure are
      assessed. In optical or diffractive superresolution the transmitted spatial
      frequency band is not so much extended as either multiplexed with or displaced
      into regions that are usually beyond reach, with no overall gain in information
      transfer because prior knowledge is used to make inferences of possible object
      structure from the image. The Uncertainty Principle for photon position and
      momentum is never disobeyed. The study of the neural substrate of visual
      hyperacuity does, however, overlap that of "geometrical superresolution," in
      which techniques are used for transcending limits imposed by the receptor lattice
      in analyzing fine image structure.

PMID- 22634485
TI  - Molecular and histological identification of the acanthocephalan Bolbosoma cf.
      capitatum from the human small intestine.
AB  - Acanthocephalans of the genus Bolbosoma are intestinal parasites of marine
      mammals with a lifecycle similar to that of anisakid nematodes. Several cases of
      Bolbosoma infection in humans have been reported, but no species identification
      has been made. Here, we report a case of Bolbosoma infection, in which the worm
      was found in histological sections of the partially resected small intestine of a
      Japanese man. Morphological features of the worm reconstructed from serial
      sectioning indicated that the worm was most likely to be a sexually immature
      female of Bolbosoma capitatum. DNA extraction from paraffin-embedded sections and
      ITS1-5.8S rRNA-ITS2 sequencing showed that this species formed a monophyletic
      group with Bolbosoma nipponicum, and was clearly distinguishable from Corynosoma
      spp. or Polymorphus spp. These results may provide a reference for identifying
      and characterizing unknown acanthocephalans found in histological sections.

PMID- 22634481
TI  - The neuroendocrine control of the circadian system: adolescent chronotype.
AB  - Scientists, public health and school officials are paying growing attention to
      the mechanism underlying the delayed sleep patterns common in human adolescents.
      Data suggest that a propensity towards evening chronotype develops during
      puberty, and may be caused by developmental alterations in internal daily
      timekeeping. New support for this theory has emerged from recent studies which
      show that pubertal changes in chronotype occur in many laboratory species similar
      to human adolescents. Using these species as models, we find that pubertal
      changes in chronotype differ by sex, are internally generated, and driven by
      reproductive hormones. These chronotype changes are accompanied by alterations in
      the fundamental properties of the circadian timekeeping system, including
      endogenous rhythm period and sensitivity to environmental time cues. After
      comparing the developmental progression of chronotype in different species, we
      propose a theory regarding the ecological relevance of adolescent chronotype, and
      provide suggestions for improving the sleep of human adolescents.

PMID- 22634486
TI  - An unusual case of an osteosarcoma arising in a leiomyoma of the uterus.
AB  - Leiomyoma is the most common uterine neoplasm. It has several histological
      variants such as atypical, cellular, myxoid, and epithelioid. Leiomyoma with
      heterologous elements is a rare variant of leiomyoma, which may contain
      heterologous elements such as fat, skeletal muscle, and chondroid and osseous
      tissues. The heterologous sarcomatous differentiation is also rarely seen. We
      report on a 53-year-old woman who was admitted with abnormal vaginal bleeding and
      symptoms related to an abdominal mass. She had a huge uterine leiomyoma that
      contained osteosarcomatous differentiation in several foci. Although malignant
      progression for leiomyoma is exceedingly rare, when it occurs it may result not
      only in a leiomyosarcoma but also in a heterologous sarcomatous differention. We
      have reported histopathological, immunohistochemical, and clinical features of
      this rare case and reviewed the published studies.

PMID- 22634487
TI  - Methanol poisoning: characteristic MRI findings.
AB  - Acute methanol intoxication is not an unusual poisoning. It can have serious
      neurological sequelae. We emphasize how neuroimaging can help in distinguishing
      methanol poisoning from other causes of acute unconsciousness in alcoholic
      patients such as hypoglycemic brain damage and carbon monoxide poisoning or head
      injury, which are frequently observed in alcoholic patients and are also
      responsible for altered sensorium. The most important findings in MR brain
      imaging in methanol poisoning have been bilateral putaminal hemorrhagic necrosis.
      Other less common findings are subcortical and deep white matter lesions,
      cerebral and cerebellar cortical lesions, and midbrain lesions, cerebral and
      intraventricular hemorrhage, and even enhancement of necrotic lesions, we found
      almost the entire spectrum of MRI findings in this patient with methanol
      poisoning. Neurological sequelae can entail the course and prognosis in methanol
      poisoning. The patient died because of ventilator-associated pneumonia that
      developed in the course of prolonged hospitalization.

PMID- 22634488
TI  - Protective effect of l-citrulline against ethanol-induced gastric ulcer in rats.
AB  - We examined the protective effect of l-citrulline on ethanol-induced gastric
      ulcer in rats. Administration of l-citrulline at doses of 300, 600 and 900mg/kg
      body weight prior to ethanol ingestion protected the stomach from ulceration. The
      gastric lesions were significantly attenuated by all doses of l-citrulline as
      compared to the ethanol group. Pre-treatment with l-citrulline prevented the
      oxidative damage and the decrease of nitric oxide content as well as the increase
      of the myeloperoxidase activity. Consequently, significant changes observed
      included the attenuation in the elevation in total nitric oxide synthase activity
      and inducible nitric oxide synthase activity as well as the decrease in
      constitutive nitric oxide synthase activity in the gastric mucosa induced by
      ethanol. Analysis of serum cytokines of ethanol-induced rats showed a moderate
      decrease in interleukin-10 with considerable increase of interleukin-6 while l
      citrulline inhibited the acute alteration of cytokines. These results suggested
      the gastroprotective effect of l-citrulline.

PMID- 22634489
TI  - Diagnosis of tuberculous cervicitis by Papanicolaou-stained smear.
AB  - Tuberculosis (TB) is a common infection in the developing countries. It can
      involve most organs. Genital TB is usually secondary to pulmonary or extragenital
      TB. Tuberculosis most commonly involves the upper genital tract. Involvement of
      the cervix is rare. In countries like India, where carcinoma of cervix is very
      common, cervical TB may easily be mistaken clinically for malignancy. We report a
      case of tuberculosis cervicits (secondary to pulmonary tuberculosis) in a 54-year
      old postmenauposal woman, who presented with a complaint of discharge per vaginum
      for a short duration. Per speculum examination showed an ulcerated lesion over
      anterior lip of cervix, clinically suggestive of malignancy. However, a
      Papanicolaou-smear showed features suggestive of tuberculosis which was confirmed
      by biopsy, resulting in early diagnosis and treatment of the patient. Hence, in a
      patient with a suspicious cervical lesion and a prior history of tuberculosis, a
      diagnosis of cervical tuberculoiss must be considered.

PMID- 22634490
TI  - Spin-orbital phase synchronization in the magnetic field-driven electron dynamics
      in a double-well potential.
AB  - We study the dynamics of an electron confined in a one-dimensional double-well
      potential in the presence of driving external magnetic  fields. The orbital
      motion of the electron is coupled to the spin dynamics by spin-orbit interaction
      of the Dresselhaus type. We derive an effective time-dependent model Hamiltonian
      for the orbital motion of the electron and obtain a condition for synchronization
      of the orbital and the spin dynamics. We find an analytical expression for the
      Arnold 'tongue' and propose an experimental scheme for realizing the proposed
      synchronization.

PMID- 22634491
TI  - Preparation of DNA-polyintercalator conjugate and its functional property.
AB  - Psoralen immobilized polyvinyl alcohol (PVA-P) was synthesized from
      chloromethylmethoxypsoralen and polyvinyl alcohol. The psoralen part of PVA-P
      intercalated into the double-stranded DNA and formed covalent bonding between the
      psoralen and nucleic acid base after 365 nm UV irradiation. As a result, DNA and
      PVA-P produced a water-insoluble conjugate. This DNA-PVA-P conjugate maintained
      the double-stranded structure of DNA and possessed the DNA's property, such as
      intercalation. Therefore, the DNA-PVA-P conjugate selectively accumulated the
      planar-structure containing chemical compounds, such as biphenyl and
      dibenzofuran, from an aqueous multi-component solution. These DNA-PVA-P
      conjugates may have the potential to be utilized as a separation material for the
      selective removal of harmful compounds.

PMID- 22634492
TI  - Revealing weak differential gene expressions and their reproducible functions
      associated with breast cancer metastasis.
AB  - Based on microarray data, a basic task is to extract differentially expressed
      (DE) genes between disease states and their associated functions to understand
      disease mechanisms. However, few such analyses have been conducted for breast
      cancer metastasis, possibly owing to the uncertainty of the disease state
      assignment for patients, which may lead to an extremely low power of detecting DE
      genes. In this study, we analyzed five datasets composed of metastatic and non
      metastatic breast primary cancer samples. For two datasets in which few DE genes
      could be detected by the conventional false discovery rate control approach, a
      clustering approach was applied to select a group of genes with large
      differential expression changes between two groups of samples, in which the
      powers of identifying DE genes increased greatly. Then, we showed that each of
      the five DE gene lists captured a part of the differential expression signals
      from which we were able to extract metastasis-associated functions non-randomly
      reproducible across different datasets. Our results highlighted that many general
      biological processes (such as 'cell division', 'cell cycle', 'microtubule-based
      processes' and 'chromosome segregation'), rather than only their sub-processes,
      may be globally altered during the course of breast cancer metastasis,
      characterizing cancer metastasis as a 'systems disease'.

PMID- 22634493
TI  - Epigenetic inactivation of DNA repair in breast cancer.
AB  - The study of epigenetic mechanisms in cancer, such as DNA methylation and histone
      modifications, has revealed a plethora of events that contribute to cancer
      through stable changes in the expression of genes critical to transformation
      pathways. In this mini review we look at the different epigenetic modifications
      prevalent in this neoplastic phenotype, focusing on breast cancer. Most
      encouragingly, research in epigenetics has led to improved survival of patients
      with certain forms of lymphoma and leukemia through the use of drugs that alter
      DNA methylation and histone acetylation. Thus, we look at the clinical utility of
      targeting epigenetic pathways. In addition, we explore numerous other clinical
      applications of epigenetics, in areas such as cancer screening and early
      detection, prevention, classification for epidemiology and prognostic purposes,
      and predicting outcomes after standard therapy.

PMID- 22634495
TI  - MicroRNA-10a targets CHL1 and promotes cell growth, migration and invasion in
      human cervical cancer cells.
AB  - MicroRNAs (miRNAs) play an important role in cancer initiation, progression and
      metastasis by regulating their target genes. Here, we found microRNA-10a (miR
      10a) is upregulated in human cervical cancer and promotes the colony formation
      activity, migration and invasion of HeLa and C33A cells. Subsequently, CHL1 is
      confirmed as a target of miR-10a and is negatively regulated by miR-10a at mRNA
      and protein levels. Furthermore, knockdown of CHL1 expression results in
      increased colony formation activity, migration and invasion. Finally,
      overexpression of CHL1 lacked the 3'UTR abolished the effects of miR-10a. Our
      results may provide a strategy for blocking tumor metastasis.

PMID- 22634494
TI  - The p53-reactivating small-molecule RITA enhances cisplatin-induced cytotoxicity
      and apoptosis in head and neck cancer.
AB  - We evaluated whether the restoration of p53 function by the p53-reactivating
      small molecule RITA (reactivation of p53 and induction of tumor cell apoptosis
      enhances cisplatin-induced cytotoxicity and apoptosis in head-and-neck cancer
      (HNC). RITA induced prominent accumulation and reactivation of p53 in a wild-type
      TP53-bearing HNC cell line. RITA showed maximal growth suppression in tumor cells
      showing MDM2-dependent p53 degradation. RITA promoted apoptosis in association
      with upregulation of p21, BAX, and cleaved caspase-3; notably, the apoptotic
      response was blocked by pifithrin-alpha, demonstrating its p53 dependence. With
      increasing concentrations, RITA strongly induced apoptosis rather than G2-phase
      arrest. In combination therapy, RITA enhanced cisplatin-induced growth inhibition
      and apoptosis of HNC cells invitro and in vivo. Our data suggest that the
      restoration of p53 tumor-suppressive function by RITA enhances the cytotoxicity
      and apoptosis of cisplatin, an action that may offer an attractive strategy for
      treating HNC.

PMID- 22634496
TI  - Gonadotropin signalling in epithelial ovarian cancer.
AB  - Ovarian cancer is the most lethal of all gynecologic malignancies, although its
      aetiology remains poorly understood. A role for the gonadotropins, follicle
      stimulating hormone (FSH) and luteinising hormone (LH), has been implicated in a
      variety of different aspects of ovarian cancer tumorigenesis, including cellular
      proliferation, migration and invasion. This review focuses on the latest advances
      in knowledge concerning signalling pathways and functional consequences of
      gonadotropin action, including changes in protein-, miRNA- and gene expression,
      in epithelial ovarian cancer cells.

PMID- 22634497
TI  - EMT in breast cancer stem cell generation.
AB  - The concept of cancer stem cells (CSCs) has been proposed to explain the ability
      of single disseminated cancer cells to reconstitute tumours with heterogeneity
      similar to that of the primary tumour they arise from. Although this concept is
      now commonly accepted, the origin of these CSCs remains a source of debate. First
      proposed to arise through stem/progenitor cell transformation, CSCs might also or
      alternatively arise from differentiated cancer cells through epithelial to
      mesenchymal transition (EMT), an embryonic transdifferentiation process. Using
      breast carcinomas as a study model, I propose revisiting the role of EMT in
      generating CSCs and the debate on potential underlying mechanisms and biological
      significance. 

PMID- 22634498
TI  - Concomitant tumor resistance.
AB  - Concomitant tumor resistance (CR) is a phenomenon in which a tumor-bearing host
      is resistant to the growth of secondary tumor implants. This phenomenon has been
      described in human and animal systems and it can be generated by both immunogenic
      and non-immunogenic tumors. The relevance of CR to the mechanisms of metastases
      control has been highlighted by numerous observations showing that the removal of
      human and murine tumors may be followed by an abrupt increase in metastatic
      growth, suggesting that a primary tumor may exert a controlling action on its
      metastases which could be considered as secondary tumor implants developed
      spontaneously during the primary tumor growth. A more profound understanding of
      the different mechanisms claimed to be associated with the phenomenon of CR could
      contribute to develop new and more harmless means to manage malignant diseases,
      especially by limiting the development of metastases that arise after resection
      of primary tumors or after other stressors that may promote the escape of
      metastases from dormancy.

PMID- 22634499
TI  - Chemoprevention: making it a success story for controlling human cancer.
AB  - Cancer chemoprevention, based on recent successes both in the laboratory and the
      clinic, is being considered as a viable option for controlling the disease. This
      approach takes advantage of the long latency of the disease that offers numerous
      opportunities for intervention. Chemopreventive intervention caters to a defined
      population that is relatively at a higher risk for developing the disease with an
      objective to stop, reverse or slow down the progression of the disease. The
      strategy of slowing the progression of cancer through chemoprevention could be
      applicable to many cancers with long latency including prostate cancer. Although
      cancer chemoprevention has proven to be a successful strategy in animals its
      application to humans has met only with limited success. This review will debate
      various challenges associated with chemoprevention of cancer and discuss ways to
      overcome them.

PMID- 22634500
TI  - Simultaneous mitochondrial Ca(2+) overload and proteasomal inhibition are
      responsible for the induction of paraptosis in malignant breast cancer cells.
AB  - In this study, we investigated the role of Ca(2+) in curcumin-induced paraptosis,
      a cell death mode that is accompanied by dilation of mitochondria and the
      endoplasmic reticulum (ER). Curcumin induced mitochondrial Ca(2+) overload
      selectively in the malignant breast cancer cells, but not in the normal breast
      cell, contributing to the dilation of mitochondria/ER and subsequent paraptotic
      cell death. In addition, we found that simultaneous inhibition of the
      mitochondrial Na(+)/Ca(2+) exchanger (mNCX) and proteasomes can trigger a
      sustained mitochondrial Ca(2+) overload and effectively induce paraptosis in
      malignant breast cancer cells.

PMID- 22634502
TI  - Pott puffy tumor: a rare complication of sinusitis.
AB  - Pott puffy tumor, a rare complication of sinusitis in adults, appears as a
      localized swelling over the frontal region or forehead. This swelling is due to a
      subperiosteal abscess resulting from osteomyelitis of the underlying frontal
      bone. This condition may be associated with an epidural purulent collection,
      subdural empyema, and intracerebral abscess. This entity is rare--even forgotten-
      since the advent of modern powerful antibiotics. A 27-year-old male was referred
      to ENT OPD with forehead swelling, fever and headache. The patient had mooth
      doughy swelling of the foreheadwith surrounding cellulitis and swelling spreading
      to the orbits as periorbital odema. On examination, patient had very poor oral
      hygiene with severe dental caries. CT with contrast conformed pansinusitis with
      erosion of frontal bone and abscess. An early recognition of this forgotten
      complication of sinusitis will help avoid severe neurological sequelae and
      increased morbidity and mortality.

PMID- 22634501
TI  - Stem cell aging and plasticity in the Drosophila nervous system.
AB  - The majority of neural stem cells (NSCs) are considered as very plastic
      precursors that, in vitro, can divide indefinitely or differentiate into neurons
      or glia under specific conditions. However, in vivo, these cells actively
      proliferate during development, and later enter quiescence or apoptosis. This
      raises the issue as to whether stem cells keep their plastic behavior throughout
      their life, which may impact their therapeutic potential in regenerative
      medicine. Using the Gcm/Glide (for Glial cell missing/Glial cell deficient)
      transcription factor, which is able to trigger a complete and stable fate
      conversion into glia when ectopically expressed, we recently reported that the
      plasticity of Drosophila NSCs, commonly called neuroblasts (NBs), is age
      dependent. When challenged with Gcm/Glide, newborn NBs are more easily converted
      into glia than old ones. Furthermore, the few old NBs that can be converted
      frequently generate cells with a stable (NB/glia) intermediate identity, a
      phenotype characteristic of cancer cells. We here discuss the concept of aging in
      NSC fate conversion and speculate on how our findings impact the ongoing debate
      concerning NSC plasticity.

PMID- 22634503
TI  - Modulation of arsenic-induced epidermal growth factor receptor pathway signalling
      by resveratrol.
AB  - Arsenic (As) is both a human carcinogen and an effective anticancer drug. These
      aspects of arsenic toxicity develop as a consequence of arsenic-induced oxidative
      stress and modifications to signal pathway activity which alter gene expression.
      Resveratrol (RVL) a food antioxidant found in grapes and other fruits, exhibits
      anti-carcinogenic properties by reducing oxidative stress and restoring signal
      pathway control. This study investigated the impact of RVL on arsenite [As(III)]
      induced cell signalling in HaCaT keratinocytes by assaying phosphorylation status
      of epidermal growth factor receptor (EGFR) signalling intermediates and measuring
      changes in expression of Phase II and DNA repair biomarkers. As(III) exposure
      produced dose-dependent toxicity which was associated with increased activation
      of EGFR pathway intermediates, cSrc, Rac1 and extracellular signal-regulated
      kinases 1 and 2 (ERK1/2). Arsenic-mediated ERK1/2 activation negatively regulated
      DNA polymerase beta expression and up regulated heme-oxygenase-1 at toxic
      concentrations. RVL treatment modulated As(III)-mediated ERK1/2 activation by
      shifting the balance of cSrc regulatory domain phosphorylation. These effects
      significantly altered the response of the EGFR pathway to growth factor-induced
      stimulation. Our research provides evidence that treatment with pharmacologically
      relevant doses of RVL influences cellular responses to As(III), largely due to
      RVL-mediated changes to Src and ERK1/2 activation.

PMID- 22634504
TI  - T-type Ca2+ signalling downregulates MEK1/2 phosphorylation and cross-talk with
      the RAAS transcriptional response in cardiac myocytes.
AB  - Cardiac dysfunction is often associated with an increase in the activity of the
      renin-angiotensin II-aldosterone system (RAAS). Here, we highlight the cross-talk
      between the Ca(2+) signalling generated by cardiac T-type current (I(CaT)) and
      RAAS signalling. Neonatal rat cardiomyocytes exposed to aldosterone, angiotensin
      II or aldosterone plus angiotensin II co-treatment (AA) show an increase in
      I(CaT) density, with no cumulative effect of the AA co-treatment. AA increases
      the amount of T-type channel Ca(v)3.1 mRNA in a time-dependent manner.
      Angiotensin II increases Ca(v)3.1 mRNA stability, whereas aldosterone increases
      the transcriptional activity of the Ca(v)3.1 gene promoter. However, in AA
      treated cells, angiotensin II decreases aldosterone-induced promoter activity,
      and aldosterone decreases angiotensin II-induced mRNA stability. The mitogen
      activated protein kinase kinase (MEK1/2), which is synergically phosphorylated in
      AA-treated cells, alters the translocation of glucocorticoid receptors (GR) into
      the nucleus and attenuates aldosterone-induced promoter activity. In contrast,
      MEK1/2 has no effect on the NFkB-induced increase in Ca(v)3.1 mRNA and MEK1/2
      promoted CREB-target gene transcription. Aldosterone and AA-induced I(CaT)
      signalling result in a time-dependent activation of the phosphatase PP2A, which
      dephosphorylates MEK1/2 and CREB. Finally, angiotensin II alone also activates
      PP2A, which targets MEK1/2, but this activation is independent of I(CaT) calcium
      signalling and has no effect on CREB phosphorylation. In conclusion, our data
      demonstrate the cross-talk between a GR-mediated aldosterone response,
      angiotensin II and the I(CaT) signalling pathways and identify MEK1/2 as a point
      of connection. This cross-talk results in the fine control of GR- and/or CREB
      target gene expression.

PMID- 22634505
TI  - Theaflavin ameliorates behavioral deficits, biochemical indices and monoamine
      transporters expression against subacute 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease.
AB  - Evidence from clinical and experimental studies indicates that degeneration of
      nigrostriatal dopaminergic neurons is a pathological hallmark of Parkinson's
      disease (PD). The present study was designed to investigate the neuroprotective
      potential of theaflavin (TF) on oxidative stress, monoamine transporters and
      behavioral abnormalities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      induced neurodegeneration. TF, a black tea polyphenol, has been known to possess
      neuroprotective effects against ischemia, Alzheimer's disease and other
      neurodegenerative disorders, but the mechanisms underlying its beneficial effects
      on MPTP-induced dopaminergic neurodegeneration are poorly defined. Administration
      of MPTP (30 mg/kg bw for four consecutive days) led to increased oxidative stress
      and reduced behavior patterns (open field, rotarod and hang test), nigrostriatal
      dopamine transporter (DAT) (immunohistochemistry and Western blot) and vesicular
      monoamine transporter 2 (VMAT2) (Western blot) expressions. Pre-treatment with TF
      reduces oxidative stress, improves motor behavior and expression of DAT and VMAT2
      in striatum and substantia nigra. These results indicate that TF might be
      beneficial in mitigating MPTP-induced damage of dopaminergic neurons, possibly
      via its neuroprotective and its antioxidant potential.

PMID- 22634506
TI  - Variable prenatal stress results in impairments of sustained attention and
      inhibitory response control in a 5-choice serial reaction time task in rats.
AB  - Rats repeatedly exposed to variable prenatal stress (PNS) exhibit schizophrenia
      like behavioral signs such as social withdrawal, elevations in amphetamine
      induced locomotor activity, deficits in sensory-motor gating, as well as
      impairments in memory-related task performance. However, to date there have been
      no studies designed to test the hypothesis that variable PNS would lead to
      disruptions in sustained attention and inhibitory response control (i.e.,
      symptoms also commonly observed in schizophrenia and other neuropsychiatric
      disorders such as attention-deficit hyperactivity disorder). In the current
      study, the effects of variable PNS in rats were evaluated in fixed and variable
      stimulus duration (VSD) as well as variable intertrial interval (VITI) versions
      of a 5-choice serial reaction time task (5C-SRTT). In a separate series of
      experiments, the glutamate (N-methyl-d-aspartate [NMDA]) antagonist, MK-801
      (0.025-0.05 mg/kg), and the norepinephrine reuptake inhibitor, atomoxetine (0.30
      3.0mg/kg), were administered acutely to assess the sensitivity of PNS subjects to
      glutamatergic and noradrenergic manipulations. The results indicated that
      exposure to variable PNS significantly impaired accuracy in the VSD version of
      the 5C-SRTT and increased premature and timeout responses in the VITI version. In
      addition, both doses of MK-801 impaired accuracy, increased premature and timeout
      responses in PNS, but not control subjects. In contrast, atomoxetine decreased
      premature and timeout responses in both PNS and control subjects in the VITI
      version of the task and improved accuracy in the PNS subjects. The results
      suggest that exposure to variable PNS in rats results in impairments of sustained
      attention and inhibitory response control and that these deficits can be
      exacerbated by NMDA antagonism and improved by a norepinephrine uptake inhibitor.
      Collectively, these data further support the premise that variable PNS in rats is
      a valid model system for the study of neuropsychiatric disorders and their
      treatment.

PMID- 22634508
TI  - Motor system modulation for movement direction and rotation angle during motor
      imagery.
AB  - Transcranial magnetic stimulation (TMS) studies have shown that the motor system
      is facilitated when we imagine performing motor actions. However, it is not clear
      whether the individual's motor system modulates bilaterally and selectively for
      task parameters, such as movement direction and amplitude. To investigate this
      issue, we applied single-pulse TMS over the left and right primary motor cortex
      (M1) of healthy subjects, who had to imagine grasping and rotating a clock hour
      hand, having a starting position at noon, towards four different times: 2, 5, 7
      and 10 o'clock. Rotations could be in clockwise (2 and 5 o'clock) or counter
      clockwise (7 and 10 o'clock) directions and could require small (2 and 10
      o'clock) or large (5 and 7 o'clock) rotation angle. TMS motor-evoked potentials
      were recorded for three muscles, and movements were imagined with the right and
      left hands. Results showed that during motor imagery a mirroring pattern was
      present between the right and the left motor cortices, showing selective
      activation of the hand-intrinsic muscles spatially close to the direction of the
      imagined movement. Overall a higher activation for large and a lower activation
      for small rotation angle were found, but no selective muscle activity was present
      within the hand-intrinsic muscles for this parameter. Following these results we
      propose that during action imagination an internally coded covariance between
      movement parameters is present with a muscle-specific activation for movement
      direction.

PMID- 22634507
TI  - Musicians have fine-tuned neural distinction of speech syllables.
AB  - One of the benefits musicians derive from their training is an increased ability
      to detect small differences between sounds. Here, we asked whether musicians'
      experience discriminating sounds on the basis of small acoustic differences
      confers advantages in the subcortical differentiation of closely related speech
      sounds (e.g., /ba/ and /ga/), distinguishable only by their harmonic spectra
      (i.e., their second formant trajectories). Although the second formant is
      particularly important for distinguishing stop consonants, auditory brainstem
      neurons do not phase-lock to its frequency range (above 1000 Hz). Instead,
      brainstem neurons convert this high-frequency content into neural response timing
      differences. As such, speech tokens with higher formant frequencies elicit
      earlier brainstem responses than those with lower formant frequencies. By
      measuring the degree to which subcortical response timing differs to the speech
      syllables /ba/, /da/, and /ga/ in adult musicians and nonmusicians, we reveal
      that musicians demonstrate enhanced subcortical discrimination of closely related
      speech sounds. Furthermore, the extent of subcortical consonant discrimination
      correlates with speech-in-noise perception. Taken together, these findings show a
      musician enhancement for the neural processing of speech and reveal a biological
      mechanism contributing to musicians' enhanced speech perception in noise.

PMID- 22634509
TI  - Regulation of hematopoietic stem cells using protein transduction domain-fused
      Polycomb.
AB  - The Polycomb-group complex is a chromatin regulatory factor that is classified
      into two different complexes: Polycomb repressive complex 1 and 2. Components of
      Polycomb repressive complex 1 are involved in the self-renewal of hematopoietic
      stem cells. Bmi1, one of these components, maintains the immaturity of neural and
      cancer stem cells as well as that of hematopoietic stem cells. We constructed
      recombinant protein transduction domain (PTD)-Polycomb proteins and transduced
      them into murine bone marrow (BM) cells. We designed and fused the PTD-protein
      transduction domain to three proteins (i.e., green fluorescent protein, Bmi1, and
      Mel18). Murine BM cells were incubated for 48 h and each PTD-Polycomb protein was
      added. Then, we analyzed the function of hematopoiesis using the colony assay and
      transplantation. BM cells exposed to PTD-Bmi1 showed an increased number of
      colonies. In contrast, BM cells exposed to PTD-Mel18 or to both proteins showed a
      decreased number of colonies. Hematopoietic cells derived from PTD-Bmi1
      transduced BM cells were significantly increased in the peripheral blood at 6
      weeks after transplantation. Moreover, 80% of mice transplanted with PTD-Bmi1
      transduced BM cells died at 8 to 24 weeks after transplantation. However, only a
      few early deaths were observed in the mice transplanted with BM cells exposed to
      both PTD-Bmi1 and PTD-Mel18. We expect that hematopoietic stem cells could
      proliferate after transduction with PTD-Bmi1, but this may generate undesirable
      effects, e.g., tumorigenesis. Thus, Bmi1 and Mel18 have opposing functions and
      are present in distinct complexes.

PMID- 22634510
TI  - Acknowledging the pioneer.

PMID- 22634511
TI  - Academy president reports:  "indebtedness".

PMID- 22634514
TI  - Ligand binding, reactivity and biological activity of a distal pocket mutant of
      neuroglobin.
AB  - We have generated the Lys67Glu mutant form of neuroglobin. Experimental spectral
      studies are consistent with a six coordinate heme in which the distal histidine
      bond is stretched compared to the wild type protein. Carbon monoxide binding to
      the ferrous form of the mutant follows a hyperbolic concentration dependence
      limiting at the histidine dissociation rate of 0.7 s(-1). Further analysis
      indicates a significantly lowered histidine binding constant. Oxygen binding
      kinetic studies confirm the higher heme ligand dissociation level and indicate a
      p50 value for oxygen binding<1 mmHg. The ferrous form of the protein yields an
      oxygenated intermediate on reaction with oxygen. The rate of oxidation, by
      oxygen, follows a complex concentration dependence, consistent with the presence
      of two distinct oxidation mechanisms. A quantitative model for the two oxidation
      processes has been developed, which is consistent with a lowered distal histidine
      binding constant in the mutant form of the protein. These data suggest that the
      protein structure surrounding the heme site in neuroglobin limits access to
      external ligands and provides an energy barrier to the structural changes
      following ligand binding in this protein. However, the mutation does not appear
      to affect reactivity with cytochrome c and the anti-apoptotic activity of the
      mutant in human cells of neuronal origin is increased as compared to the wild
      type protein.

PMID- 22634515
TI  - Flavonoid aglycones can compete with Ochratoxin A for human serum albumin: a new
      possible mode of action.
AB  - The mycotoxin Ochratoxin A (OTA) appears worldwide in cereals, plant products,
      different foods and drinks. Ochratoxin A binds to plasma albumin with a very high
      affinity. However, it is well known that natural flavonoids can also bind to
      human serum albumin (HSA) at the same binding site as OTA does (site I, subdomain
      IIA). A few experimental literature data suggest that reducing the bound fraction
      of OTA speeds up its elimination rate with a potential decrease in its toxicity.
      In our experimental model competitive binding properties of flavonoid aglycones
      were examined with a fluorescence polarization based approach. Our data show that
      some of the flavonoids are able to remove the toxin from HSA. We conclude that
      among the 13 studied flavonoid aglycones galangin and quercetin were the most
      effective competitors for OTA.

PMID- 22634516
TI  - Dilute solution properties of Balangu (Lallemantia royleana) seed gum: effect of
      temperature, salt, and sugar.
AB  - The interaction between hydrocolloids and solvent/cosolutes are the predominant
      factors determining their functional properties in food systems. In this
      research, the influence of different temperatures, salts and sugars were
      investigated on some molecular parameters of Balangu seed gum (BSG) as a new
      potential source of hydrocolloid. The results revealed that BSG has a high
      molecular weight (3.65 * 10(6)g/mole) and intrinsic viscosity (7236.18 ml/g),
      rather flexible chain with a chain flexibility parameter of 1156.53, low
      stiffness parameter (0.346 for Na(+) and 0.507 for Ca(2+)) and hydrogel content
      (46%). It was observed that except for water, the solutions of different salts
      (NaCl and CaCl(2)) and sugars (sucrose and lactose) are poor solvents for BSG as
      indicated by a monotonous decrease in intrinsic viscosity, swollen specific
      volume, shape function, hydration parameter, and coil dimensions. The parameters
      representing the interactions of BSG molecules with different cosolutes, i.e.
      hydrogel content and Huggins constant, were observed to increase significantly as
      the ionic strength and sugar concentrations increased from 0.005 to 0.05 M and
      2.5 to 40% w/v, respectively. In addition, the elevated temperatures (20-50 
      degrees C) induced a clear contraction in BSG dimensional and shape parameters
      along with a decrease in solvent quality and the extent of associated water
      molecules through hydrogen bonds and/or physical entrainment. These results may
      be of high significance when considering the influence of major additives
      generally used in food products, such as various salts and sugars, and/or
      frequent processing parameters like temperature on rheological and functional
      points of view.

PMID- 22634517
TI  - The enhancing effect of homocysteine thiolactone on insulin fibrillation and
      cytotoxicity of insulin fibril.
AB  - In the current study both structural alteration and fibrillation of insulin were
      studied in the presence of homocysteine thiolactone (HCTL). The spectroscopic
      studies revealed that HCTL increases rate of insulin unfolding, giving rise to
      the appearance of solvent-exposed hydrophobic regions and induces a transition
      from alpha-helix into predominantly beta-sheet structures. Thioflavin-T
      fluorescence studies revealed that HCTL markedly enhanced the quantity of insulin
      fibril formation in both agitating and non-agitating systems. Also gel
      electrophoresis results suggest that HCTL accelerates the process of formation of
      high molecular weight insulin aggregates. Moreover, insulin fibrils obtained in
      the presence of HCTL and those collected earlier in the pathway of insulin
      fibrillation displayed improved cytotoxicity against cancer cells. The
      enhancement of insulin fibril formation with elevated cytotoxic properties as
      occurred in the presence of HCTL, may suggest this homocysteine derivative as a
      possible contributing factor in the pathology of insulin fibrils.

PMID- 22634518
TI  - Oxidized phospholipid content destabilizes the structure of reconstituted high
      density lipoprotein particles and changes their function.
AB  - High density lipoprotein (HDL) particles are made up of lipid and protein
      constituents and apolipoprotein A-I (apoA-I) is a principal protein component
      that facilitates various biological activities of HDL particles. Increase in Ox
      PL content of HDL particles makes them 'dysfunctional' and such modified HDL
      particles not only lose their athero-protective properties but also acquire pro
      atherogenic and pro-inflammatory functions. The details of Ox-PL-induced
      alteration in the molecular properties of HDL particles are not clear.
      Paraoxonase 1 (PON1) is an HDL-associated enzyme that possesses anti-inflammatory
      and anti-atherogenic properties; and many of the athero-protective functions of
      HDL are attributed to the associated PON1. In this study we have characterized
      the physicochemical properties of reconstituted HDL (rHDL) particles containing
      varying amounts of Ox-PL and have compared their PON1 stimulation capacity. Our
      results show that increased Ox-PL content (a) modifies the physicochemical
      properties of the lipid domain of the rHDL particles, (b) decreases the stability
      and alters the conformation as well as orientation of apoA-I molecules on the
      rHDL particles, and (c) decreases the PON1 stimulation capacity of the rHDL
      particles. Our data indicate that the presence of Ox-PLs destabilizes the
      structure of the HDL particles and modifies their function.

PMID- 22634519
TI  - A study of diagnostic methods for Marteilioides chungmuensis infections in the
      Pacific oyster Crassostrea gigas.
AB  - The eggs of the Pacific oyster, Crassostraea gigas, become infertile when
      infected by the parasite Marteilioides chungmuensis. Histologically, M.
      chungmuensis infects the oyster oocyte cytoplasm, and the ovaries take on a
      "lumpy" appearance once infected, which lowers commercial value of the oyster.
      This has a negative economic impact on oyster farms in South Korea and Japan. In
      this study, we compared traditional diagnostic methods (histology) with two
      molecular-based methods (polymerase chain reaction [PCR] amplification and in
      situ hybridization [ISH]) to identify M. chungmuensis-infected oysters. The
      efficacy of PCR and ISH to identify M. chungmuensis-infected oysters was compared
      to that of routine histology in 100 oysters. Thirty infections were identified
      using PCR and 16 using histology, whereas 31 infections were identified using
      ISH. The ISH and PCR assays were more sensitive compared to using histology with
      standard epidemiological methods. We strongly recommend that early parasitic
      invasion should be monitored with PCR/ISH methodologies as a basis for developing
      effective diagnostic techniques to identify M. chungmuensis-infected oysters.

PMID- 22634520
TI  - Should a 'psychosis risk syndrome' be a separate diagnosis in DSM-5?

PMID- 22634521
TI  - What has been learned from joint working between mental health professionals,
      patients and users of psychiatric services, their families and friends?
AB  - PURPOSE OF REVIEW: To outline what is known about collaborative work between the
      main stakeholders in mental health and psychiatry (professionals, patients or
      service users and family members). To learn from recent practice what are the
      main areas of joint work, what is working well, what are the key issues and
      problems and what has been learned from doing it. RECENT FINDINGS: Service users
      and family members are valued in education and training. Service users as peer
      support workers have helped patients recover, and methods of participatory
      research can bring new insights. There is a need to support and build an evidence
      base for these new ways of working. SUMMARY: The run-down of institutions, the
      new paradigm of recovery and human rights laws have led to increased joint
      working in the field of law and policy, research, education and training, service
      provision and coercion. Joint working challenges the old ways of knowledge
      creation and practices such as coercive treatment. More work is needed to build
      on what is being learned and move to genuine equality and partnership.

PMID- 22634522
TI  - Parenting quality and children's mental health:  biological mechanisms and
      psychological interventions.
AB  - PURPOSE OF REVIEW: The quality of parenting that children receive can have a
      profound influence on their development and mental health. This article reviews
      articles published from late 2010 onwards that address the effects of parenting
      on the child's physiological and genetic systems, and how interventions can
      improve children's security of attachments, antisocial behaviour and other
      outcomes across a range of settings. RECENT FINDINGS: Biological indices of
      stress, such as C-reactive protein, show that prenatal anxiety is a significant
      determinant of later outcomes for children, and abusive parenting of young
      children has lasting biological effects into adulthood. Increasingly, specific
      genes, especially those that code for neurotransmitter synthesis and functions,
      are being identified that moderate parenting effects. Furthermore, animal studies
      suggest that harsh parenting affects the expression of genes by epigenetic
      processes.Parenting programmes are effective in increasing the security of infant
      children's attachments, and reducing conduct problems/antisocial behaviour in
      childhood, and they can be effective at a population level in preventing abuse.
      These programmes are now widening their reach to cover a broader range of
      children's outcomes such as literacy and obesity. SUMMARY: We are learning much
      more about the biological impact of poor parenting and the need for interventions
      that are crafted to improve the quality of parent-child relationships in many
      settings. Hopefully, they will also ameliorate the biological effects of poor
      parenting.

PMID- 22634523
TI  - Association study of IRAK-M and SIGIRR genes with SLE in a large European-descent
      population.
AB  - OBJECTIVE: The aim of this study was to evaluate the relevance of genetic
      variants of interleukin receptor-associated kinase-M (IRAK-M) (rs11465955,
      rs1624395, rs1152888 and rs1370128) and single immunoglobulin IL1-1R-related
      molecule (SIGIRR) (rs3210908) genes in systemic lupus erythematosus (SLE) in four
      independent European-descent populations. METHODS: Our study population consisted
      of a total of 2033 SLE patients and 2357 healthy controls from Spain, Germany,
      Italy and Argentina. The genotyping was performed using a polymerase chain
      reaction (PCR) system with pre-developed TaqMan allelic discrimination assay.
      Genetic association between the genotyped markers was determined by PLINK v1.07.
      RESULTS: After a meta-analysis including these four populations, a trend of
      association between rs11465955 (P(meta) (-analysis)  = 0.06), rs1370128 (P(meta)
      (-analysis)  = 0.07) and rs1624395 (P(meta) (-analysis)  = 0.06) polymorphisms
      was found. However, these differences did not reach statistical significance. In
      addition, we did not find any association between SLE and the rs1152888 IRAK-M
      (P(meta) (-analysis)  = 0.13) and the rs3210908 SIGIRR (P(meta) (-analysis)  =
      0.40) polymorphisms after the meta-analysis. No evidence of association with IRAK
      M haplotypes was found. CONCLUSION: These results suggest that the tested
      variations of IRAK-M and SIGIRR genes do not confer a relevant role in the
      susceptibility to SLE in European-descent populations.

PMID- 22634524
TI  - Comparative distribution of protein components of the A20 ubiquitin-editing
      complex in normal human brain.
AB  - Activation of innate and adaptive immune responses is tightly regulated, as
      insufficient activation could result in defective clearance of pathogens, while
      excessive activation might lead to lethal systemic inflammation or autoimmunity.
      A20 functions as a negative regulator of innate and adaptive immunity by
      inhibiting NF-kappaB activation. A20 mediates its inhibitory function in a
      complex with other proteins including RNF11 and Itch, both E3 ubiquitin ligases
      and TAX1BP1, an adaptor protein. Since NF-kappaB has been strongly implicated in
      various neuronal functions, we predict that its inhibitor, the A20 complex, is
      also present in the nervous system. In efforts to better understand the role of
      A20 complex and NF-kappaB signaling pathway, we determined regional distribution
      of A20 mRNA as well as protein expression levels and distribution of RNF11,
      TAX1BP1 and Itch, in different brain regions. The distribution of TRAF6 was also
      investigated since TRAF6, also an E3 ligase, has an important role in NF-kappaB
      signaling pathway. Our investigations, for the first time, describe and
      demonstrate that the essential components of the A20 ubiquitin-editing complex
      are present and mainly expressed in neurons. The A20 complex components are also
      differentially expressed throughout the human brain. This study provides useful
      information about region specific expression of the A20 complex components that
      will be invaluable while determining the role of NF-kappaB signaling pathway in
      neuronal development and degeneration.

PMID- 22634525
TI  - Electrical stimulation of cerebellar fastigial nucleus promotes the expression of
      growth arrest and DNA damage inducible gene beta and motor function recovery in
      cerebral ischemia/reperfusion rats.
AB  - This study focused on the effects of electrical stimulation of cerebellar
      fastigial nucleus on the expression of growth arrest and DNA damage inducible
      gene beta (Gadd45beta) and on motor function recovery after focal cerebral
      ischemia/reperfusion (I/R) in rats. Sprague-Dawley (SD) rats were randomly
      divided into 4 groups: sham I/R (control group), I/R (I/R group), I/R with sham
      stimulation and I/R with electrical stimulation at 6h, 12h, 24h, 2d and 3d after
      I/R. Cerebral ischemia and reperfusion was established by nylon monofilament
      occlusion method. Fastigial nucleus (FN) electrical stimulation was applied at 2h
      after ischemia for 1h. The changes in the expression of Gadd45beta were analyzed
      by immunohistochemistry, real-time polymerase chain reaction (PCR) and Western
      blot respectively. Another group of rats were divided into the same 4 groups.
      Montoya staircase test score was used to test the motor function of affected
      forelimb. The levels of Gadd45beta were significantly elevated after I/R injury.
      FN electrical stimulation treatment elevated the expression of Gadd45beta further
      and improved motor function recovery. These results suggest that FN electrical
      stimulation can promote the expression of Gadd45beta and motor function recovery
      after focal cerebral ischemia.

PMID- 22634527
TI  - Evolution of tumour biology upon progression. Do we know our enemy?

PMID- 22634526
TI  - The RhoGEF Zizimin-related acts in the Drosophila cellular immune response via
      the Rho GTPases Rac2 and Cdc42.
AB  - Zizimin-related (Zir), a Rho guanine nucleotide exchange factor (RhoGEF)
      homologous to the mammalian Dock-C/Zizimin-related family, was identified in a
      screen to find new genes involved in the Drosophila melanogaster cellular immune
      response against eggs from the parasitoid wasp Leptopilina boulardi. RhoGEFs
      activate Rho-family GTPases, which are known to be central regulators of cell
      migration, spreading and polarity. When a parasitoid wasp is recognized as
      foreign, multiple layers of circulating immunosurveillance cells (haemocytes)
      should attach to the egg. In Zir mutants this process is disrupted and
      lamellocytes, a haemocyte subtype, fail to properly encapsulate the wasp egg.
      Furthermore, macrophage-like plasmatocytes exhibit a strong reduction in their
      ability to phagocytise Escherichia coli and Staphylococcus aureus bacteria.
      During encapsulation and phagocytosis Zir genetically interacts with two Rho
      family GTPases, Rac2 and Cdc42. Finally, Zir is dispensable for the humoral
      immune response against bacteria. We propose that Zir is necessary to activate
      the Rho-family GTPases Rac2 and Cdc42 during the Drosophila cellular immune
      response.

PMID- 22634528
TI  - Merkel cell carcinoma: what do we know about it and what should we do?
AB  - Merkel cell carcinoma (MCC) is a rare primary cutaneous carcinoma of the skin
      that is highly aggressive, and has a high risk of locoregional and distant
      spread, a mortality rate considerably higher than that of cutaneous melanoma and
      poor survival. Its incidence has increased during the past twenty years. The
      studies published since 2008 have introduced changes in the understanding of its
      epidemiology and pathogenesis, and consequently the therapeutic approach. Despite
      this, there is still controversy surrounding its optimal management, which
      requires clarification. This is the purpose of this review.

PMID- 22634529
TI  - Chemotherapy-induced nausea and vomiting: pathophysiology and therapeutic
      principles.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is a major determinant of quality
      of life in cancer patients. In addition, the perceptions that oncology
      professionals have about CINV quite often do not coincide with reality.
      Antineoplastic agents and their combinations can be categorised according to
      their emetogenic level, and this categorisation is helpful for classifying the
      severity of CINV and treating it. All CINV treatment guidelines emphasise the
      need to administer prophylaxis to patients who receive highly or moderately
      emetogenic chemotherapy. With the introduction of NK1 receptor antagonists, the
      control of acute and delayed CINV after highly or moderately emetogenic
      chemotherapy schedules has improved in the great majority of patients. NK1
      receptor antagonists have been demonstrated to improve the control of CINV in all
      risk subgroups of patients.

PMID- 22634530
TI  - Functions and workload of medical oncologists in Spain.
AB  - The functions and workload of medical oncologists are becoming increasingly
      relevant as cancer is a priority health issue in our country. Taking into account
      the specific characteristics and complexity of caring for cancer patients, the
      time of physicians attached to Medical Oncology could be distributed as follows:
      70% for consultation (including participation in tumour committees and
      multidisciplinary units), 15% for research and 15% for training, teaching and
      clinical sessions. The time distribution for Heads of Services or Heads of Units
      is different, since it must also include their clinical management tasks, team
      coordination, and relations with other services and institutions. The average
      time, calculated in minutes, spent on each activity per patient is as follows:
      first visit and "second visit or results visit" 60-90 min; successive visits at
      the day hospital 15 min; successive visits of patients for follow-up or checkups
      20 min; visits with family members 15-20 min; telephone or e-mail consultations 5
      10 min; hospitalisation 20 min; and interconsultation 30-60 min. Also,
      participation in multidisciplinary committees takes up 60-120 min of an
      oncologist's time each week. When new technologies such as electronic medical
      records, e-mail and other software are used, these times increase with a
      correction factor that is still to be defined and which could vary according to
      the centre. Finally, the ratio recommended by SEOM is one medical oncologist for
      every 83 new patients a year.

PMID- 22634531
TI  - Classical markers like ER and ki-67, but also survivin and pERK, could be
      involved in the pathological response to gemcitabine, adriamycin and paclitaxel
      (GAT) in locally advanced breast cancer patients: results from the GEICAM/2002-01
      phase II study.
AB  - INTRODUCTION: The identification and validation of biomarkers of chemotherapy
      sensitivity is critical in order to individualise therapy in breast cancer. We
      evaluated pathological complete response (pCR) to GAT, and its correlation with
      tumour biomarkers before and after neoadjuvant chemotherapy. MATERIALS AND
      METHODS: Stage III (and stage II with T>=5 cm) breast cancer patients were
      included. Treatment consisted of adriamycin (40 mg/m(2)) day 1, and paclitaxel
      (150 mg/ m(2)) followed by gemcitabine (2000 mg/m(2)) day 2, every 14 days for
      six cycles. Tissue from pre-treatment biopsy and surgery was evaluated for
      biologic markers by immunohistochemistry. Two XPD single nucleotide polymorphisms
      (SNP) were also analysed. RESULTS: Forty-six patients entered the trial. Median
      age was 49.5 years (range 31-72); 25 patients (54%) were pre-menopausal; 12 (26%)
      were ER-PgR-negative; pCR was observed in 17% (95% CI: 6.4-28.4) of patients.
      Significant differences in marker expression (mean+/-SD) in correlation to
      pathological response were only found in Ki- 67. After treatment, tumours showed
      lower Ki-67-, surviving- and pERK-positive cells. No correlation between XPD
      polymorphisms and pCR was found. The overall response rate was 89% (95% CI: 80.1
      98.1). Fifteen patients (33%) underwent breast-conserving surgery. The most
      frequent grade 3 or 4 toxicities were neutropenia (with one febrile neutropenia)
      and asthenia. CONCLUSION: These results show an effective regimen with acceptable
      tolerability. Our data suggest that not only classical markers (ER, Ki-67), but
      also survivin and pERK could be involved in the response to GAT, which may
      contribute to therapy individualisation in future study designs.

PMID- 22634532
TI  - Clinical study on the recombinant human endostatin regarding improving the blood
      perfusion and hypoxia of non-small-cell lung cancer.
AB  - OBJECTIVE: To observe the dynamic changes of blood perfusion and hypoxic status
      with CT perfusion imaging and hypoxia imaging in patients of non-small-cell lung
      cancer (NSCLC) who were treated with recombinant human endostatin (RHES).
      METHODS: Fifteen previously untreated patients with histologically or
      cytologically confirmed NSCLC were enrolled. They were randomly divided into
      research group (n=10) and negative control group (n=5). The patients of the
      research group continuously used RHES for ten days, and simultaneously had CT
      perfusion imaging and hypoxia imaging performed on days 1, 5 and 10,
      respectively. The remaining 5(control) only had CT perfusion imaging and hypoxia
      imaging, without using RHES, on days 1, 5 and 10, respectively. According to the
      above results, we could obtain a "time window" during which RHES improves blood
      perfusion and hypoxia of lung cancer. RESULTS: In the research group, after using
      RHES, capillary permeability surface (PS) and tumour to normal tissue (T/N)
      decreased at first, and then increased. Their lowest points occurred on about the
      fifth day with statistical significance compared with the first day (T/N, p=0.00;
      PS, p<0.01). Blood flow (BF) was first increased and then decreased. Its highest
      point occurred on about the fifth day with statistical significance compared with
      the first and tenth day (all p<0.01). The PS, BF and T/N peaked on the fifth day
      in the research group with statistical significance compared with the negative
      control group as well (all p<0.01). The above results suggested that RHES's "time
      window" was within about one week after administration. CONCLUSION: RHES's "time
      window" is within about one week after administration, which provides an
      important experimental basis for combining RHES with radiotherapy in human
      tumours.

PMID- 22634533
TI  - Expanding Sca-1(+) mammary stem cell in the presence of oestrogen and growth
      hormone.
AB  - BACKGROUND: Sca-1 is controversial as a mammary stem cell marker in the
      literature, which may be due to the different isolation protocols and culture
      media used in different laboratories. The object of our study is to establish the
      Medium to promote the proliferation of mammary stem cell and explore the
      possibility of Sca-1 as mammary stem cell marker. METHODS: We used BM medium
      supplemented with different concentration of 17Beta-oestradiol and GH to find out
      MaECM medium which promoted the proliferation of mouse mammary epithelial cells
      and inhibited the growth of fibroblasts. Flow cytometry was used to isolate Sca
      1(+) and Sca-1(-) cell populations from cultured mammary epithelial cells.
      Mammary fat pad transplantation and Mammosphere- forming assay were done to
      confirm the stem cell potential of Sca-1(+) cells. Differentiating culture was
      used to detect the differentiation potential of Sca-1(+) cells. Real-time PCR was
      carried out to analyse the expression of mammary stem cell-related genes in Sca
      1(+) cells. RESULTS: We first selected the medium suitable for mammary stem cell
      growth. Stem cell medium BM was used to culture mammary organoids, which
      generated many fibroblasts. We established MaECM medium supplemented with
      oestrogen and growth hormone (GH), in which oestrogen promoted mammary epithelial
      cell proliferation and inhibited fibroblast growth, and GH obviously enhanced the
      effect of oestrogen on mammary epithelial cell proliferation. Flow cytometry
      showed that 50% of cells were Sca-1(+) under the culture of MaECM medium. We
      confirmed that Sca-1(+) cells regenerated mammary outgrowths when transplanted in
      vivo, formed mammospheres in vitro and differentiated into luminal epithelial
      cells with milk-secreting function and myoepithelial cells under Matrigel
      culture. Furthermore, gene expression analysis by Real-time PCR revealed that Sca
      1(+) cells expressed markedly higher levels of mammary stem cell-related genes in
      comparison to Sca-1(-) cells. CONCLUSION: Our research demonstrates that Sca-1(+)
      mammary stem cells can be more easily isolated when cultured in the presence of
      oestrogen and GH.

PMID- 22634534
TI  - Biological markers of cisplatin resistance in advanced testicular germ cell
      tumours.
AB  - INTRODUCTION: Germ cell tumours (GCTs) of the testis show exquisite sensitivity
      to treatment with cisplatin. Despite the high cure rates provided by platinum
      based chemotherapy, 10-20% of patients die from progressive disease. Although
      various cellular pathways may influence cisplatin efficacy, their actual impact
      has not been comprehensively investigated in advanced GCTs. The objective of the
      present study was to clarify the role of the expression status of proteins
      involved in the Rb and p53 tumour suppressor pathways in sensitivity and
      resistance of GCTs to cisplatin-based chemotherapy. MATERIALS AND METHODS:
      Paraffin-embedded tumour tissues from 84 patients with advanced GCT treated with
      cisplatin-based chemotherapy were analysed. Immunohistochemical expression of
      proteins p53 and mdm2, and the G1-phase cyclins D1 and D2 (CD1 and CD2) was
      assessed and correlated with the clinical course. RESULTS: The percentages of
      positive expression of p53, mdm2, CD1 and CD2 were 56, 57, 37.5 and 55%,
      respectively. From univariate analysis, there was no significant association
      between p53, mdm2 or CD1 expression and outcome. Instead, positive CD2 expression
      was found to be marginally associated with shorter median duration of progression
      free survival (PFS) (p=0.06). In multivariate analysis, none of the molecular
      markers retained statistical significance with treatment response or survival.
      CONCLUSIONS: Tissular expression of p53, mdm2 and CD1 is not associated with
      prognosis or treatment response in patients with advanced GCT. Aberrant CD2
      expression appears to further determine a shorter PFS. Larger and further studies
      are required to validate CD2 as a marker of cisplatin resistance.

PMID- 22634536
TI  - Preliminary clinical study of weekly recombinant human endostatin as a hypoxic
      tumour cell radiosensitiser combined with radiotherapy in the treatment of NSCLC.
AB  - OBJECTIVE: To investigate the clinical effects and adverse effects of weekly
      recombinant human endostatin (RHES) as a hypoxic tumour cell radiosensitiser
      combined with radiotherapy in the treatment of non-small-cell lung cancer
      (NSCLC). METHODS: Fifty hypoxia-positive cases of pathology-diagnosed NSCLC
      (stage I-III) were randomly divided into a RHES+radiotherapy group (25 cases) and
      a radiotherapy alone group (25 cases). Intensity-modulated radiotherapy (IMRT)
      with a total dose of 60 Gy/30F/6W was adopted in the two groups. Target area
      included primary foci and metastatic lymph nodes. In the RHES+radiotherapy group,
      RHES (15 mg/day) was intravenously given during the first week. The therapeutic
      effects and adverse reactions were evaluated after treatment. RESULTS: In the
      RHES+radiotherapy and radiotherapy alone groups, the total effective rates
      (CR+PR) were 80% and 44% (chi(2)=6.87, p=0.009), respectively. The one-year and
      two-year local control rates were (78.9+/-8.4)% and (68.1+/-7.8)% (p=0.027), and
      (63.6+/-7.2)% and (43.4+/-5.7)% (p=0.022), respectively. The median progression
      free survival was (21.1+/-0.97) and (16.5+/-0.95) months, respectively. The one
      year and two-year overall survival rates were (83.3+/-7.2)% and (76.6+/-9.3)%
      (p=0.247), and (46.3+/-2.4)% and (37.6+/-9.1)% (p=0.218), respectively.
      CONCLUSION: RHES combined with radiotherapy within the first week has better
      short-term therapeutic effects and local control rate, and no severe adverse
      reactions in treatment of NSCLC. However, it failed to significantly improve the
      one-year and two-year overall survival rates.

PMID- 22634535
TI  - Trends in prostate cancer survival in Spain: results from population-based cancer
      registries.
AB  - INTRODUCTION: The aim of this study is to analyse the evolution of the survival
      of patients diagnosed with prostate cancer during the period 1995-2003. MATERIAL
      AND METHODS: This is a population survival study of incident cases of prostate
      cancer in four Spanish areas: Basque Country, Girona, Murcia and Navarra. We
      calculated the relative survival (RS) at 5 years and its 95% confidence intervals
      using a cohort analysis and adjusted for age. To assess the trend in survival
      between the periods (1995-1999 and 2000-2003) a Poisson regression model was
      used, adjusting for age, region and period, obtaining the relative risk of death.
      RESULTS: The number of patients diagnosed during the 1995- 1999 period was 6493
      and 8331 in the period 2000-03. The RS at 5 years adjusted for age increased
      significantly, from 75.3% (95% CI 73.3-77.2) in the period 1995-99 to 85% (95% CI
      83.4-86.4) in the period 2000-03. CONCLUSION: In Spain the survival of patients
      with prostate cancer has increased significantly from 1999 to 2003, probably due
      to the advancement in diagnosis produced by the opportunistic screening of
      prostate-specific antigen (PSA). Differences in the dissemination and use of the
      PSA level could explain the observed geographic differences in the increase of
      survival. It would be necessary to carry out studies to quantify the produced
      overdiagnosis by screening with PSA in prostate cancer.

PMID- 22634537
TI  - Long-term results with oral fluoropyrimidines and oxaliplatin-based preoperative
      chemoradiotherapy in patients with resectable rectal cancer. A single-institution
      experience.
AB  - INTRODUCTION: Neoadjuvant 5-FU-based chemoradiotherapy in resectable rectal
      cancer (RC) is a standard of treatment. The use of oral fluoropyrimidines and new
      agents such as oxaliplatin may improve efficacy and tolerance. MATERIAL AND
      METHODS: Between 1999 and 2009, 126 RC patients with T3-T4 and/or N+ disease were
      given three successive protocols: UFT (32), UFT-oxaliplatin (75) and capecitabine
      oxaliplatin (19), alongside 45 Gy of radiotherapy; with surgery 4-6 weeks after.
      Adjuvant treatment was given in all patients. The primary objective was
      pathologic complete response (pCR). RESULTS: Preoperative therapy was well
      tolerated, with no toxic deaths and a 15% grade 3-4 toxicity rate. Eighty-five
      percent of patients received the full chemotherapy dose, 56% had an
      abdominoperineal resection, 6% reinterventions and 57% received the full adjuvant
      chemotherapy planned. The pCR rate was 13%. The downstaging rate was 80%; 8% had
      progression of disease. The relapse rate was 20%, with local relapse in 6%. By 5
      years of followup, 92% of relapses had occurred. Median follow-up was 73 months,
      5- and 10-year disease-free survival rates were 75% and 50%, and 5- and 10-year
      overall survival rates were 79% and 66% respectively. There was no benefit from
      the use of oxaliplatin regarding survival or pCR rates. Older patients had worse
      long-term outcomes. CONCLUSIONS: Neoadjuvant chemoradiotherapy with oral
      fluoropyrimidines and oxaliplatin is feasible and well tolerated. The risk of
      early progression is low. However, there was no added benefit with the use of
      oxaliplatin. There were no relapses in patients with pCR. The role of adjuvant
      chemotherapy is unclear.

PMID- 22634538
TI  - Behaviour of breast cancer molecular subtypes through tumour progression.
AB  - INTRODUCTION Breast cancer (BC) becomes more aggressive throughout disease
      progression. Clinical stage is correlated with patient outcome. We hypothesised
      that BC molecular subtypes are associated with a poor prognosis in advanced
      clinical stages. We analysed the distribution and behaviour of molecular subtypes
      at different BC tumour size and variation of molecular subtype in recurrent
      lesions. PATIENTS AND METHODS: We studied 1647 consecutive patients with non
      metastatic invasive and microinvasive (Tmi) BC treated from January 1997 to
      December 2007. Patients were categorised by tumour size and molecular subtype. A
      chi-square method was used for multiple group comparisons. Kaplan-Meier product
      limit method was used to calculate overall survival and disease-free survival.
      RESULTS: Median follow-up was 7.2 years. For patients with invasive BC the median
      age was 56 years. Four hundred and fifteen patients recurred and 225 died. Larger
      tumours were more frequently of triple-negative (TN) subtype than small ones or
      Tmi lesions. Any molecular subtype change from primary tumour to recurrent
      lesions is more likely to happen from a good prognosis to a subtype of worse
      prognosis than the opposite. Larger tumours of luminal A, luminal B and TN, but
      not HER2 subtype, are more likely to carry aggressive markers and to have worse
      outcomes than small ones. CONCLUSION: We found accumulation of TN subtype,
      migration to a poor prognosis subtype and increasing aggressiveness of luminal
      and TN subtypes throughout tumour progression. Tumours belonging to the HER2
      subtype behave aggressively regardless of the primary size.

PMID- 22634539
TI  - Relevance of breast cancer subtypes for magnetic resonance imaging response
      monitoring during neoadjuvant chemotherapy.
AB  - Changes in magnetic resonance imaging (MRI) during neoadjuvant chemotherapy (NAC)
      have been reported as predictive of pathology outcome in triple-negative and HER2
      positive breast cancer. The purpose of our study was to evaluate the relevance of
      breast cancer subtype for MRI response in 24 women before and during NAC in our
      centre. Our results show that a reduction greater than 23% is associated with a
      pathological complete response (pCR) in Her-2-positive and ER-negative/Her2
      negative breast cancer, and suggest a trend correlation between higher ADC values
      and pCR in these subtypes in comparison with ER-positive/Her2-negative breast
      cancers. Higher proliferating tumours respond better to chemotherapy and our
      study suggests that changes in MRI during NAC are predictive of pCR in these
      breast cancer subtypes.

PMID- 22634540
TI  - Brain abscesses complicating acute pneumococcal meningitis during etanercept
      therapy.
AB  - Brain abscess formation as a sequelae of community-acquired pneumococcal
      meningitis is extremely rare, accounting for less than 1% of all meningitis
      complications. Although metastatic seeding from a distal peripheral septic focus
      has been observed, this phenomenon most commonly occurs in the context of ear,
      nose and throat infections, post-cranial neurosurgical procedures, traumatic open
      cranial injury, or immunosuppression. We present the case of a man, 61 years old,
      on etanercept therapy for ankylosing spondylitis who developed multiple brain
      abscesses as a complication of pneumococcal meningitis. We believe that the
      predisposition to this extremely rare complication of a particularly aggressive
      pneumococcal meningitis was most likely due to the underlying immunosuppression
      resulting from etanercept therapy. As far as we know, this case is the first
      report linking multiple brain abscess formation in a patient with community
      acquired pneumococcal meningitis with etanercept therapy.

PMID- 22634541
TI  - Evaluation of a mitochondrial DNA mutation in maternally inherited and sporadic
      cases of Dupuytren disease.
AB  - OBJECTIVE: The purpose was to test the hypothesis that Dupuytren disease (DD) is
      associated with a previously reported mutation in mitochondrial DNA at position
      2839. METHODS: Two hundred sixty-nine cases of DD and an equal number of matched
      controls were identified in Marshfield Clinic's Personalized Medicine Research
      Project (PMRP). Clinical data used to describe the cohort were abstracted from
      the electronic medical records of the population. Genetic analysis of all the
      cases and controls was done using a custom synthesis TaqMan assay, while genetic
      analysis of sixteen of the above cases with a familial history of DD was
      performed by mitochondrial DNA sequencing at position C2839A. RESULTS: Cases and
      controls were evenly distributed with 167 (62%) men and 102 (38%) women. The
      majority, 264 (98%) of the cases and controls were white non-Hispanic. Of the 269
      cases, 16 were found to have a familial history of DD. Two cases had a maternal
      history, eight a paternal history, five an affected sibling, and one a paternal
      grandfather. All cases and controls were found to have only the C allele at the
      site of the reported mitochondrial C2839A polymorphism. CONCLUSIONS: The
      previously reported mitochondrial mutation was not present in our small,
      maternally inherited cohort or in the total population of 538 cases and controls.
      This finding does not support the reported incidence of this polymorphism in 90%
      of the affected population with a maternal inheritance, and calls into question
      the role of the C2839A mitochondrial DNA polymorphism in familial or sporadic
      cases of DD.

PMID- 22634543
TI  - A simple and robust way of concluding meta-analysis results using reported P
      values, standardized effect sizes, or other statistics.
AB  - Meta-analysis is a powerful tool to estimate measures of associations or effects
      based on published or unpublished reports. However, problems exist in many meta
      analyses, particularly related to study heterogeneity. This article proposes a
      way of concluding meta-analysis results using P values, taking heterogeneity into
      account. There is little published research focused on evaluating conclusiveness
      of summary results of reported meta-analyses. Generally, a P value is directly
      linked to the test statistic z=b/s(b) following a standard normal distribution
      with mean zero and unit variance, where b is an estimator of beta and s(b) is the
      estimated standard error of b for any study included in a meta-analysis. This
      forms the basis of the proposed method for deriving overall test statistics and
      corresponding P values used for comparing results of meta-analyses. Two published
      meta-analyses were chosen and specific software was applied. Results are
      consistent with the two published meta-analysis reports in terms of P values for
      significance and direction of summary measure of treatment effect. This proposed
      method can be utilized to safeguard against improper conclusions of published
      meta-analyses due to heterogeneity. Exploring more sophisticated statistical
      methods for situations when the key assumption applied to this proposed method is
      violated could be pursued and could expand the scope of applications beyond this
      method.

PMID- 22634542
TI  - Towards automatic diabetes case detection and ABCS protocol compliance
      assessment.
AB  - OBJECTIVE: According to the American Diabetes Association, the implementation of
      the standards of care for diabetes has been suboptimal in most clinical settings.
      Diabetes is a disease that had a total estimated cost of $174 billion in 2007 for
      an estimated diabetes-affected population of 17.5 million in the United States.
      With the advent of electronic medical records (EMR), tools to analyze data
      residing in the EMR for healthcare surveillance can help reduce the burdens
      experienced today. This study was primarily designed to evaluate the efficacy of
      employing clinical natural language processing to analyze discharge summaries for
      evidence indicating a presence of diabetes, as well as to assess diabetes
      protocol compliance and high risk factors. METHODS: Three sets of algorithms were
      developed to analyze discharge summaries for: (1) identification of diabetes, (2)
      protocol compliance, and (3) identification of high risk factors. The algorithms
      utilize a common natural language processing framework that extracts relevant
      discourse evidence from the medical text. Evidence utilized in one or more of the
      algorithms include assertion of the disease and associated findings in medical
      text, as well as numerical clinical measurements and prescribed medications.
      RESULTS: The diabetes classifier was successful at classifying reports for the
      presence and absence of diabetes. Evaluated against 444 discharge summaries, the
      classifier's performance included macro and micro F-scores of 0.9698 and 0.9865,
      respectively. Furthermore, the protocol compliance and high risk factor
      classifiers showed promising results, with most F-measures exceeding 0.9.
      CONCLUSIONS: The presented approach accurately identified diabetes in medical
      discharge summaries and showed promise with regards to assessment of protocol
      compliance and high risk factors. Utilizing free-text analytic techniques on
      medical text can complement clinical-public health decision support by
      identifying cases and high risk factors.

PMID- 22634544
TI  - Drosophila eye color mutants as therapeutic tools for Huntington disease.
AB  - Huntington disease (HD) is a fatal inherited neurodegenerative disorder caused by
      a polyglutamine expansion in the huntingtin protein (htt). A pathological
      hallmark of the disease is the loss of a specific population of striatal neurons,
      and considerable attention has been paid to the role of the kynurenine pathway
      (KP) of tryptophan (TRP) degradation in this process. The KP contains three
      neuroactive metabolites: 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN), and
      kynurenic acid (KYNA). 3-HK and QUIN are neurotoxic, and are increased in the
      brains of early stage HD patients, as well as in yeast and mouse models of HD.
      Conversely, KYNA is neuroprotective and has been shown to be decreased in HD
      patient brains. We recently used a Drosophila model of HD to measure the
      neuroprotective effect of genetic and pharmacological inhibition of kynurenine
      monoxygenase (KMO)-the enzyme catalyzing the formation of 3-HK at a pivotal
      branch point in the KP. We found that KMO inhibition in Drosophila robustly
      attenuated neurodegeneration, and that this neuroprotection was correlated with
      reduced levels of 3-HK relative to KYNA. Importantly, we showed that KP
      metabolites are causative in this process, as 3-HK and KYNA feeding experiments
      modulated neurodegeneration. We also found that genetic inhibition of the
      upstream KP enzyme tryptophan-2,3-dioxygenase (TDO) was neuroprotective in flies.
      Here, we extend these results by reporting that genetic impairment of KMO or TDO
      is protective against the eclosion defect in HD model fruit flies. Our results
      provide further support for the possibility of therapeutic KP interventions in
      HD.

PMID- 22634545
TI  - Evaluation of Magainin I interactions with lipid membranes: an optical and
      electrochemical study.
AB  - Most antimicrobial peptides (AMPs) have shown clear activity related to the
      disruption of lipid bilayers. In order to improve knowledge of this subject, the
      interaction of Magainin I (MagI) with phospholipid layers (PLs), uncoated or
      coated with synperonic (Synp), was studied using cyclic voltammetry (CV),
      electrochemical impedance spectroscopy (EIS) and surface plasmon resonance (SPR)
      techniques. MagI peptide was immobilized on gold electrode via a self-assembling
      monolayer obtained from liposomes and liposomes covered by Synp. MagI induces
      pores in the supported lipid membranes, which are reflected in an increased
      amperometric-response and also a decreased electron-transfer resistance (R(CT)).
      In addition, MagI showed a significant interaction with the PL-Synp-modified gold
      electrode, but MagI showed a reliable contact with the PL-modified gold
      electrode, leading to a decrease in the relative resistance charge transfer value
      of -17.38%. Our results demonstrated that Synp acts as a membrane sealant after
      exposure of the lipid membrane to MagI. A parallel reaction model was proposed
      for the interaction of MagI and a hybrid layer that result in a complex
      bimolecular interaction. In short, the importance of triblock copolymer to
      stabilize liposomes for future applications as drug delivery systems for MagI was
      demonstrated.

PMID- 22634546
TI  - Potassium channels underlie postsynaptic but not presynaptic GABAB receptor
      mediated inhibition on ventrolateral periaqueductal gray neurons.
AB  - gamma-Aminobutyric acid (GABA) is the principle inhibitory neurotransmitter in
      adult mammalian brain. GABA receptors B subtype (GABA(B)Rs) are abundantly
      expressed at presynaptic and postsynaptic neuronal structures in the rat
      ventrolateral periaqueductal gray (PAG), an area related to pain regulation.
      Activation of GABA(B)Rs by baclofen, a selective agonist, induces presynaptic
      inhibition by decreasing presynaptic glutamate release. At the same time,
      baclofen induces a postsynaptic inhibitory membrane current or potential. We here
      report that in the ventrolateral PAG, the postsynaptic inhibition is mediated by
      activation of G protein-coupled inwardly rectifying K(+) (GIRK) channels.
      Blockade of K(+) channels largely prevents postsynaptic action of baclofen. In
      contrast, presynaptic inhibition of baclofen is insensitive to K(+) channel
      blockade. The data indicate that potassium channels play different roles in
      GABA(B)R-mediated presynaptic and postsynaptic inhibition on PAG neurons.

PMID- 22634547
TI  - Transverse dispersion and interfacial dephasing effects on the shape and
      amplitude of the ballistic-electron-emission spectroscopy of nanographenes.
AB  - We investigate charge transport across metal-molecule-metal junctions, i.e.
      hexagonal and triangular nanographene molecular layers sandwiched between Pt and
      Pd thin films, as measured by ballistic-electron-emission spectroscopy (BEEM).
      The measured shape of current-voltage curves cannot be explained in the framework
      of existing BEEM theories of bulk inorganic semiconductors. We develop a tight
      binding model for the BEEM process and propose that the energetic dispersion of
      molecular layers and the dephasing effect due to the interface states account for
      the anomalous BEEM current-voltage behavior and play an important role in
      determining the shape of the curve. The electron-phonon scattering can also
      affect the shape of current-voltage curves.

PMID- 22634548
TI  - Ectopic nephrogenic rest in the inguinal canal in a 6-month-old girl and a review
      of published studies.
AB  - Ectopic nephrogenic rests in the inguinal canal are rare. Usually discovered
      incidentally during surgery, these rests should raise the suspicion of an early
      extrarenal Wilms tumor. The differential diagnosis between the two entities is
      not only difficult but also essential, since they imply different treatment
      decisions. We report a rare case of an inguinal ectopic nephrogenic rest found in
      a 6-month-old girl and discuss the clinicopathological implications of this
      condition. The patient was admitted for a routine repair of a presumed inguinal
      hernia; during surgery, a nodular mass was noted in the inguinal canal.
      Pathological diagnosis confirmed the diagnosis of an extrarenal hyperplastic
      nephrogenic rest. Five previous cases of ectopic nephrogenic rests originating in
      the inguinal canal have been reported, all of which were associated with a patent
      processus vaginalis. In this case, the nephrogenic rest was not associated with a
      congenital inguinal hernia.

PMID- 22634549
TI  - Flexibility of GroES mobile loop is required for efficient chaperonin function.
AB  - Chaperonin GroEL and its partner GroES assist the folding of nascent and stress
      damaged proteins in an ATP-dependent manner. Free GroES has a flexible "mobile
      loop" and binds to GroEL through the residues at the tip of the loop, capping the
      central cavity of GroEL to provide the substrate polypeptide a cage for secure in
      cage folding. Here, we show that restriction of the flexibility of the loop by a
      disulfide cross-linking between cysteines within the loop results in the
      inefficient formation of a stable GroEL-polypeptide-GroES ternary complex and
      inefficient folding. Then, we generated substrate proteins with enhanced binding
      affinity to GroEL by fusion of one or two SBP (strongly binding peptide for
      GroEL) sequences and examined the effect of disulfide cross-linking on the
      assisted folding. The results indicate that the higher the binding affinity of
      the substrate polypeptide to GroEL, the greater the contribution of the mobile
      loop flexibility to efficient in-cage folding. It is likely that the flexibility
      helps GroES capture GroEL's binding sites that are already occupied by the
      substrate polypeptide with various binding modes.

PMID- 22634550
TI  - A Bayesian approach for calculating variable total maximum daily loads and
      uncertainty assessment.
AB  - To account for both variability and uncertainty in nonpoint source pollution, one
      dimensional water quality model was integrated with Bayesian statistics and load
      duration curve methods to develop a variable total maximum daily load (TMDL) for
      total nitrogen (TN). Bayesian statistics was adopted to inversely calibrate the
      unknown parameters in the model, i.e., area-specific export rate (E) and in
      stream loss rate coefficient (K) for TN, from the stream monitoring data. Prior
      distributions for E and K based on published measurements were developed to
      support Bayesian parameter calibration. Then the resulting E and K values were
      used in water quality model for simulation of catchment TN export load, TMDL and
      required load reduction along with their uncertainties in the ChangLe River
      agricultural watershed in eastern China. Results indicated that the export load,
      TMDL and required load reduction for TN synchronously increased with increasing
      stream water discharge. The uncertainties associated with these estimates also
      presented temporal variability with higher uncertainties for the high flow regime
      and lower uncertainties for the low flow regime. To assure 90% compliance with
      the targeted in-stream TN concentration of 2.0mgL(-1), the required load
      reduction was determined to be 1.7 * 10(3), 4.6 * 10(3), and 14.6 * 10(3)kg TNd (
      1) for low, median and high flow regimes, respectively. The integrated modeling
      approach developed in this study allows decision makers to determine the required
      load reduction for different TN compliance levels while incorporating both flow
      dependent variability and uncertainty assessment to support practical adaptive
      implementation of TMDL programs.

PMID- 22634551
TI  - Assessment of health risks with reference to oxidative stress and DNA damage in
      chromium exposed population.
AB  - Trivalent chromium [Cr(III)] is widely used in tanning industrial processes. The
      population living in tanning industrial area is continuously exposed to Cr(III)
      which appears to be associated with both acute and chronic health problems.
      Therefore, the aim of this study was to evaluate the health risk with special
      reference to oxidative stress parameters (malondialdehyde - MDA, glutathione -
      GSH, and superoxide dismutase - SOD) and DNA damage in 100 Cr-exposed and 100
      unexposed populations. The total blood Cr level, SOD level, MDA level and DNA
      damage were significantly (p<0.05) higher and GSH level was significantly
      (p<0.05) lower in exposed group as compared to the unexposed group. The altered
      oxidative stress parameters and DNA damage were found to be slightly higher in
      female population of both groups. In simple and multiple correlation analyses
      (adjusted with potential confounders), blood Cr level showed negative significant
      correlation with GSH level and positive significant correlation with level of
      MDA, SOD and DNA damage in both groups. The overall prevalence of morbidity was
      found to be significantly (p<0.05) higher in the exposed group as compared to the
      unexposed group. In the exposed group, the prevalence of respiratory illness is
      highest, followed by diabetes, gastrointestinal tract problems and dermal
      problems respectively. Our results concluded that the Cr(III) exposed population
      is at high risk for health hazards and the female population is slightly more
      susceptible to Cr(III) exposure.

PMID- 22634552
TI  - Dampness and moulds in workplace buildings: associations with incidence and
      remission of sick building syndrome (SBS) and biomarkers of inflammation in a 10
      year follow-up study.
AB  - There are few longitudinal studies on health effects of dampness and moulds in
      workplace buildings. We studied associations between dampness and indoor moulds
      in workplace buildings and selected biomarkers as well as incidence and remission
      of sick building syndrome (SBS). The study was based on a ten-year prospective
      study (1992-2002) in a random sample of adults (N=429) from the Uppsala part of
      the European Community Respiratory Health Survey (ECRHS). The 10-year incidence
      (onset) of general, mucosal, dermal symptoms and any symptom improved when away
      from the workplace (work-related symptoms) was 7.2%, 11.6%, 6.4% and 9.4%
      respectively. The 10-year remission of general, mucosal, dermal symptoms and work
      related symptoms was 71.4%, 57.1%, 70.4% and 72.2% respectively. Signs of
      dampness in the floor construction in any workplace building during follow up
      (cumulative exposure) was associated with incidence of mucosal symptoms
      (OR=2.43). Cumulative exposure to moldy odor was associated with incidence of
      work-related symptoms (OR=2.69). Cumulative exposure to dampness or moulds was
      associated with decreased remission of work-related symptoms (OR=0.20 for water
      leakage, OR=0.17 for floor dampness, and OR=0.17 for visible indoor mould
      growth). Working in a building repaired because of dampness (repaired building)
      or mould was associated with decreased remission of work-related symptoms
      (OR=0.32). Any dampness or moulds at baseline in the workplace building was
      associated with increased bronchial responsiveness (BR) and higher levels of
      Eosinphilic Cationic Protein (ECP) in serum and Eosinophilic counts in blood at
      baseline. Cumulative exposure to dampness and moulds, and work in a repaired
      building, was associated with increased BR at follow-up. In general, dampness and
      moulds in the workplace building is associated with increased incidence and
      decreased remission of SBS, as well as increased bronchial responsiveness and
      eosinophilic inflammation.

PMID- 22634553
TI  - Reductive dechlorination of chlorinated hydrocarbons as non-aqueous phase liquid
      (NAPL): preliminary investigation on effects of cement doses.
AB  - The reactivities of various types of iron mixtures to degrade chlorinated
      hydrocarbons (PCE, TCE and 1,1,1-TCA) in the form of non-aqueous phase liquids
      were investigated. The iron mixtures included a mixture of Fe(II) and Portland
      cement (Fe(II)-C), a mixture of Fe(II), Fe(III) and Ca(OH)(2) (Fe(II/III)-L), and
      a mixture of Fe(II), Fe(III), Ca(OH)(2), and Portland cement (Fe(II/III)-C). When
      the same amount of Fe(II) was used, Fe(II)-C was more reactive with chlorinated
      ethylenes (i.e. PCE and TCE) than Fe(II/III)-L. The reductive pathway for high
      concentrations of total PCE (i.e. above solubility) with Fe(II)-C was determined
      to be a combination of two-electron transfer, beta-elimination and
      hydrogenolysis. Increasing the cement dose from 5% to 10% in Fe(II)-C did not
      affect PCE dechlorination rates, but it did favor the beta-elimination pathway.
      In addition, when Fe(II/III)-C with 5%C was used, PCE dechlorination was similar
      to that by Fe(II)-C, but this mixture did not effectively degrade TCE. A modified
      second-order kinetic model was developed and shown to appropriately describe
      degradation of TCE at high concentrations. Fe(II/III)-L effectively degraded high
      concentrations of 1,1,1-TCA at rates that were similar to those obtained with
      Fe(II)-C using 10% C. Moreover, both increasing cement doses and the presence of
      Fe(III) increased dechlorination rates of 1,1,1-TCA, which was mainly through the
      hydrogenolysis pathway. The reactivity of Fe(II/III)-L was strongly dependent on
      the target compound (i.e. less reactivity with TCE, more with 1,1,1-TCA).
      Therefore, Fe(II/III)-L could be a potential mixture for degrading 1,1,1-TCA, but
      it should be modified to degrade TCE more effectively.

PMID- 22634554
TI  - A new improved study of cyanotoxins presence from experimental cyanobacteria
      concentrations in the Trasona reservoir (Northern Spain) using the MARS
      technique.
AB  - Cyanotoxins, a kind of poisonous substances produced by cyanobacteria, are
      responsible for health risks in drinking and recreational water uses. The aim of
      this study is to improve our previous and successful work about cyanotoxins
      prediction from some experimental cyanobacteria concentrations in the Trasona
      reservoir (Asturias, Northern Spain) using the multivariate adaptive regression
      splines (MARS) technique at a local scale. In fact, this new improvement consists
      of using not only biological variables, but also the physical-chemical ones. As a
      result, the coefficient of determination has improved from 0.84 to 0.94, that is
      to say, more accurate predictive calculations and a better approximation to the
      real problem were obtained. Finally the agreement of the MARS model with
      experimental data confirmed the good performance.

PMID- 22634555
TI  - Assessing nitrification and denitrification in a paddy soil with different water
      dynamics and applied liquid cattle waste using the 15N isotopic technique.
AB  - Using livestock wastewater for rice production in paddy fields can remove
      nitrogen and supplement the use of chemical fertilizers. However, paddy fields
      have complicated water dynamics owing to varying characteristics and would
      influence nitrogen removal through nitrification followed by denitrification.
      Quantification of nitrification and denitrification is of great importance in
      assessing the influence of water dynamics on nitrogen removal in paddy fields. In
      this study, nitrification and nitrate reduction rates with different water
      dynamics after liquid cattle waste application were evaluated, and the in situ
      denitrification rate was determined directly using the (15)N isotopic technique
      in a laboratory experiment. A significant linear regression correlation between
      nitrification and the nitrate reduction rate was observed and showed different
      regression coefficients under different water dynamics. The regression
      coefficient in the continuously flooded paddy soil was higher than in the drained
      reflooded paddy soil, suggesting that nitrate would be consumed faster in the
      flooded paddy soil. However, nitrification was limited and the maximum rate was
      only 13.3 MUg Ng(-1)day(-1) in the flooded paddy soil with rice plants, which
      limited the supply of nitrate. In contrast, the drained-reflooded paddy soil had
      an enhanced nitrification rate up to 56.8 MUg Ng(-1)day(-1), which was four times
      higher than the flooded paddy soil and further stimulated nitrate reduction
      rates. Correspondingly, the in situ denitrification rates determined directly in
      the drained-reflooded paddy soil ranged from 5 to 1035 mg Nm(-2)day(-1), which
      was higher than the continuously flooded paddy soil (from 5 to 318 mg Nm(-2)day(
      1)) during the vegetation period. The nitrogen removal through denitrification
      accounted for 38.9% and 9.9% of applied nitrogen in the drained-reflooded paddy
      soil and continuously flooded paddy soil, respectively.

PMID- 22634556
TI  - Ragweed pollen observed in Turkey: detection of sources using back trajectory
      models.
AB  - This paper discusses the pollen season and the source apportionment of ragweed
      (Ambrosia) grains detected in the atmosphere of Istanbul, Turkey. The dynamic
      migration of this invasive taxon is a serious environmental issue. Ragweed pollen
      is highly allergenic and causes sensitization in patients at low concentrations.
      At present, there is no floristic evidence of this taxon in the region.
      Aerobiological records presented here, though, indicate a local source. Moreover,
      we argue that ragweed pollen comes from distant sources through air mass
      movements. The analysis concerns the ragweed season 2007. Pollens were sampled
      with a Burkard trap and identified at a magnification of 400 *. Grains were
      counted on 12 transverse traverses to estimate bi-hourly changes in
      concentrations. The peak day was on August 28 with 20 grainsm(-3). Ragweed was
      observed on 22 days during August and September 2007. On all days, except one,
      the daily average concentration was below 10 grainsm(-3). Diurnal bi-hourly
      ragweed concentrations reached a maximum at 11:00 EET. Relatively high
      concentrations were observed between 21:00 and 01:00 EET. This allowed for the
      assumption of a local and a remote ragweed pollen source. We used HYSPLIT
      backward trajectory ensembles to identify possible sources on peak day. A
      frequency analysis of back trajectories covering the entire ragweed season
      followed. Firstly, possible local sources were the Istanbul Province and Turkish
      Thrace; secondly, a likely over-regional source was Bulgaria; and lastly, remote
      sources of ragweed pollen were the Ukraine, the Russian coastal region of the
      Black Sea and Moldova. This study provides evidence that pollens detected on our
      receptor site stem from combined local and remote origins.

PMID- 22634557
TI  - Hospital effluent: investigation of the concentrations and distribution of
      pharmaceuticals and environmental risk assessment.
AB  - A study was conducted in an area in north, Italy, on the effluent of two
      different sized hospitals and the influent and effluent of the receiving
      municipal treatment plant of one of the examined hospitals. The aim was to
      investigate 73 selected pharmaceuticals, belonging to twelve different classes,
      comparing their occurrence in the effluent directly exiting the hospital with
      that, mixed with the local urban effluent, at the point of its entry and exit
      from the treatment plant. Consistent differences were found in the concentrations
      of some antibiotics, analgesics and lipid regulators in the two wastewaters,
      confirming that hospital effluents should not be considered as possessing the
      same pollutant nature as urban wastewater. Furthermore, analysis of percentage
      contributions of the hospital to the treatment plant influent evidences that
      hospitals represent one of the main sources of pollutants, in particular
      antibiotics, receptor antagonists and lipid regulators. Hence, an environmental
      risk assessment, performed on the effluent from the hospital and the influent and
      effluent from the treatment plant, revealed a high risk for 9 pharmaceuticals in
      hospital effluent and for 4 of the 9 substances in the treatment plant influent
      and effluent, with antibiotics being the most critical compounds in terms of
      contribution and potential environmental risk for the hospital.

PMID- 22634558
TI  - The occurrence of steroidal estrogens in south-eastern Ontario wastewater
      treatment plants.
AB  - We measured steroidal estrogens in wastewater in Ottawa and Cornwall (Ontario,
      Canada) to determine removal efficiency of these steroids during the treatment
      process, and whether removal varies during a seasonal cycle. Estrone (E1), 17beta
      estradiol (E2) and 17alpha-ethinylestradiol (EE2) were found at maximum
      concentrations in raw sewage (RS), at 104, 66.9 and 5.7 ng L(-1), respectively.
      For the Ottawa wastewater treatment plant (WWTP), there was sufficient data to
      show that E1 concentrations in RS correlated with both ambient air temperature
      and mean daily flow of the WWTP (R(2)=0.792, p=0.003 and R(2)=0.757, p=0.005). E1
      removal was correlated with the percent difference in cBOD from RS to FE (final
      effluent) (R(2)=0.435, p=0.075). However estrogenic potency, as determined by a
      sensitive in vitro reporter gene assay, did not decrease during the water
      treatment process, suggesting that many estrogenic chemicals are conserved in FE.
      E1 and EE2 were found in river water, both upstream and downstream of the WWTPs,
      and at much lower concentrations than in FE. Our study demonstrates the
      persistence of steroidal estrogens and estrogenic potency in Ontario WWTP
      effluents and surface waters, and has uncovered temporal patterns of release that
      may be used to help predict risks to aquatic organisms in these environments.

PMID- 22634559
TI  - Spatial estimation of antibiotic residues in surface soils in a typical intensive
      vegetable cultivation area in China.
AB  - Antibiotic residues in surface soils can lead to serious health risks and
      ecological hazards. Spatial mean concentration of antibiotic residues in the soil
      is the most important indicator of a region's environmental risk to antibiotic
      residues. Considerable estimation error would lead to an inefficient strategy of
      pollution control that happens when sample size is small and the estimation model
      does not match the spatial features of the object to be surveyed. On the basis of
      the available datasets, it was found that the distribution of antibiotics residue
      in soil follows a spatial stratification pattern. Accordingly, we used a new
      spatial estimation method called Mean of Surface with Non-homogeneity (MSN) to
      estimate antibiotic concentrations in surface soil of the Shandong Province, an
      important vegetable growing region in China. The standard error of the mean
      estimates obtained by MSN was significantly smaller (by about 1.02-6.82 MUg/kg)
      than the estimation errors produced by three mainstream methods, simple
      arithmetic estimation (2.9-11.8 MUg/kg), stratified estimation (2.5-10.6 MUg/kg)
      and ordinary kriging estimation (2.2-8.2 MUg/kg).

PMID- 22634560
TI  - A method coupled with remote sensing data to evaluate non-point source pollution
      in the Xin'anjiang catchment of China.
AB  - Non-point source (NPS) pollution has been recognized as the largest threat to
      water resources throughout the world, and the evaluation of NPS loads is a
      priority. In China, some models, such as SWAT (Soil and Water Assessment Tools)
      model, have been widely used at the watershed scale. However, variations in
      natural and social factors make it difficult to find a proper model to use on NPS
      pollution management in China. In this study, a "Dualistic Structure" model is
      coupled with remote sensing data to capture the spatial and temporal processes of
      NPS pollution. Land parameters were derived from HJ-1A and HJ-1B satellite data
      (resolution 30 m), which offered greatly enhanced spatial resolution. This
      approach offers the advantage of being a rapid estimation system with fairly
      precise knowledge of the distribution, sources and quantities of NPS pollutants,
      and it can be used at the country scale, including in areas with insufficient
      data. The method is used in the Xin'anjiang catchment, an important water source
      for Hangzhou city, China. The simulation in this study includes the spatial
      distribution of monthly total nitrogen (TN), total phosphorous (TP), ammonia
      nitrogen (NH(4)-N) and chemical oxygen demand (COD(cr)) loads and the total
      production of NPS pollutants. The simulations were compared to pollution census
      (PC) data in 2010 and the results of SWAT model, with an average R(2) larger than
      0.7. Additionally, the impacts of soil erosion and human activities on NPS
      pollution were assessed, indicating that soil and water conservation is very
      significant factor in the Xin'anjiang catchment. Results indicate that by
      coupling remote sensing data and parameter retrieval techniques to "Dualistic
      Structure" models, estimations of NPS loads on the catchment scale can be
      improved by spatial pixel-based modeling. This rapid NPS estimation system will
      offer effective support to policy makers for environmental management in China.

PMID- 22634561
TI  - The importance of appropriate temporal and spatial scales for dengue fever
      control and management.
AB  - It is important to have appropriate models for the surveillance and control of
      mosquito-borne diseases, such as dengue fever (DF). These models need to be based
      on appropriate temporal and spatial scales. The aim of this study was to
      illustrate the impact of different temporal and spatial scales on DF control
      decisions. We applied the Getis-Ord Gi* statistic at different temporal and
      spatial scales to examine the local level of spatial clusters at these scales in
      order to identify and visualize areas where numbers of adult female Aedes
      mosquitoes were extreme and geographically homogenous. The modeled hotspot areas
      were different, depending on whether they were modeled on weekly, monthly or
      yearly aggregated data. A similar result was found when using different spatial
      scales for modeling, with different scales giving different hotspot regions. For
      2006, the highest risk areas (18 districts) were mostly identified in the central
      districts with a high rate of similarity (95%) compared to the highest risk areas
      (19) identified in the averaged five-year period model. Knowledge of appropriate
      temporal and spatial scales can provide an opportunity to specify the health
      burden of DF and its vector within the hotspots, as well as set a platform that
      can help to pursue further investigations into associated factors responsible for
      increased disease risk based on different temporal and spatial scales.

PMID- 22634562
TI  - The aryl hydrocarbon receptor ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3
      methylcholanthrene regulate distinct genetic networks.
AB  - The two estrogen receptor isoforms ERalpha and ERbeta mediate biological effects
      of estrogens, but are also targets for endocrine disruptive chemicals (EDCs),
      compounds that interfere with hormonal signaling. 3-Methylcholanthrene (3-MC) and
      dioxin (TCDD) are EDCs and prototypical aryl hydrocarbon receptor (AhR) agonists,
      and can inhibit ER signaling. However, in contrast to TCDD, 3-MC gives rise to
      metabolites with estrogenic properties. We compared gene expression profiles in
      HepG2 cells after exposure to 3-MC, TCDD, and the synthetic estrogen
      diethylstilbestrol (DES). Interestingly, we observed little overlap between the
      genetic networks activated by 3-MC and TCDD, two compounds sometimes considered
      as interchangeable AhR ligands. Like DES, 3-MC induced a number of ER-regulated
      genes and lead to recruitment of ERalpha to the promoters of such genes.
      Interestingly, in contrast to DES, the estrogenic effects exerted by 3-MC were
      exclusively observed in ERalpha, but not in ERbeta-expressing cells, suggesting
      ER isoform selectivity of 3-MC-derived metabolites.

PMID- 22634563
TI  - Optimization of affinity, specificity and function of designed influenza
      inhibitors using deep sequencing.
AB  - We show that comprehensive sequence-function maps obtained by deep sequencing can
      be used to reprogram interaction specificity and to leapfrog over bottlenecks in
      affinity maturation by combining many individually small contributions not
      detectable in conventional approaches. We use this approach to optimize two
      computationally designed inhibitors against H1N1 influenza hemagglutinin and, in
      both cases, obtain variants with subnanomolar binding affinity. The most potent
      of these, a 51-residue protein, is broadly cross-reactive against all influenza
      group 1 hemagglutinins, including human H2, and neutralizes H1N1 viruses with a
      potency that rivals that of several human monoclonal antibodies, demonstrating
      that computational design followed by comprehensive energy landscape mapping can
      generate proteins with potential therapeutic utility.

PMID- 22634564
TI  - Isolation of primitive endoderm, mesoderm, vascular endothelial and trophoblast
      progenitors from human pluripotent stem cells.
AB  - To identify early populations of committed progenitors derived from human
      embryonic stem cells (hESCs), we screened self-renewing, BMP4-treated and
      retinoic acid-treated cultures with >400 antibodies recognizing cell-surface
      antigens. Sorting of >30 subpopulations followed by transcriptional analysis of
      developmental genes identified four distinct candidate progenitor groups. Subsets
      detected in self-renewing cultures, including CXCR4(+) cells, expressed primitive
      endoderm genes. Expression of Cxcr4 in primitive endoderm was confirmed in
      visceral endoderm of mouse embryos. BMP4-induced progenitors exhibited gene
      signatures of mesoderm, trophoblast and vascular endothelium, suggesting
      correspondence to gastrulation-stage primitive streak, chorion and allantois
      precursors, respectively. Functional studies in vitro and in vivo confirmed that
      ROR2(+) cells produce mesoderm progeny, APA(+) cells generate
      syncytiotrophoblasts and CD87(+) cells give rise to vasculature. The same
      progenitor classes emerged during the differentiation of human induced
      pluripotent stem cells (hiPSCs). These markers and progenitors provide tools for
      purifying human tissue-regenerating progenitors and for studying the commitment
      of pluripotent stem cells to lineage progenitors.

PMID- 22634566
TI  - Proteomics, a new tool for farm animal science.

PMID- 22634567
TI  - Solitary metachronous gastric metastasis from pulmonary adenocarcinoma: Report of
      a case.
AB  - INTRODUCTION: Gastric metastases from lung adenocarcinoma are rare and usually
      associated with disseminated disease. The great majority is asymptomatic and in
      few cases discovered during autopsy studies. Reports of single metachronous
      metastases during the lifetime are anecdotal. We describe a case of solitary
      gastric metastasis 5 years after lung surgery. PRESENTATION OF CASE: A 68-year
      old male submitted in 2006 to right lobectomy for lung adenocarcinoma was
      referred at Emergency Room department in 01/2011 because of chronic epigastric
      pain. Radiologic and endoscopic evaluation showed a bulky lesion inside the
      stomach, originating from the muscular layer, suspected for GIST. He underwent a
      subtotal gastrectomy and the pathologic examination revealed an undifferentiated
      adenocarcinoma, positive for Thyroid Transcriptional Factor-1, Cytokeratin 7, AE
      1/3 and CEA, confirming the pulmonary origin. DISCUSSION: At the time of
      diagnosis about 50% of lung cancer are metastatic, with survival rates of 1% at 5
      year. Gastric metastasis is very rare; autopsy studies report an incidence of 0.2
      0.5%. They develop in the submucosa, usually without any symptom and the
      diagnosis is incidental during the staging of primary cancer or the follow-up.
      There are no guidelines about surgical treatment; however few cases of long-term
      survival following the operation were reported. Pathologic diagnosis is
      difficult, but the immunohistochemical staining helps to recognize the primary
      origin. CONCLUSION: Solitary metachronous gastric metastasis from pulmonary
      adenocarcinoma is an exceptional event, but it could happen during the follow-up.
      It seems that a radical resection, in absence of systemic implants, might provide
      survival benefits in selected patients.

PMID- 22634565
TI  - Cloning and expression analysis of Fgf5, 6 and 7 during early chick development.
AB  - FGFs with similar sequences can play different roles depending on the model
      organisms examined. Determining these roles requires knowledge of spatio-temporal
      Fgf gene expression patterns. In this study, we report the cloning of chick Fgf5,
      6 and 7, and examine their gene expression patterns by whole mount in situ
      hybridization. We show that Fgf5's spatio-temporally restricted expression
      pattern indicates a potentially novel role during inner ear development. Fgf6 and
      Fgf7, although belonging to different subfamilies with diverged sequences, are
      expressed in similar patterns within the mesoderm. Alignment of protein sequences
      and phylogenetic analysis demonstrate that FGF5 and FGF6 are highly conserved
      between chick, human, mouse and zebrafish. FGF7 is similarly conserved except for
      the zebrafish, which has considerably diverged.

PMID- 22634568
TI  - A novel evaluation of World No Tobacco day in Latin America.
AB  - BACKGROUND: World No Tobacco Day (WNTD), commemorated annually on May 31, aims to
      inform the public about tobacco harms. Because tobacco control surveillance is
      usually annualized, the effectiveness of WNTD remains unexplored into its 25th
      year. OBJECTIVE: To explore the potential of digital surveillance (infoveillance)
      to evaluate the impacts of WNTD on population awareness of and interest in
      cessation. METHODS: Health-related news stories and Internet search queries were
      aggregated to form a continuous and real-time data stream. We monitored daily
      news coverage of and Internet search queries for cessation in seven Latin
      American nations from 2006 to 2011. RESULTS: Cessation news coverage peaked
      around WNTD, typically increasing 71% (95% confidence interval [CI] 61-81),
      ranging from 61% in Mexico to 83% in Venezuela. Queries indicative of cessation
      interest peaked on WNTD, increasing 40% (95% CI 32-48), ranging from 24% in
      Colombia to 84% in Venezuela. A doubling in cessation news coverage was
      associated with approximately a 50% increase in cessation queries. To gain a
      practical perspective, we compared WNTD-related activity with New Year's Day and
      several cigarette excise tax increases in Mexico. Cessation queries around WNTD
      were typically greater than New Year's Day and approximated a 2.8% (95% CI -0.8
      to 6.3) increase in cigarette excise taxes. CONCLUSIONS: This novel evaluation
      suggests WNTD had a significant impact on popular awareness (media trends) and
      individual interest (query trends) in smoking cessation. Because WNTD is
      constantly evolving, our work is also a model for real-time surveillance and
      potential improvement in WNTD and similar initiatives.

PMID- 22634569
TI  - Tobacco industry's ITGA fights FCTC implementation in the Uruguay negotiations.
AB  - OBJECTIVE: To illustrate how the tobacco industry' front group, the International
      Tobacco Growers Association (ITGA), mobilised tobacco farmers to influence the
      fourth session of the Conference of the Parties (COP4) negotiations and defeat
      the adoption of Framework Convention on Tobacco Control Articles 9 and 10
      Guidelines and Articles 17 and 18 progress report. METHODS: A review of COP4
      documents on Articles 9, 10, 17 and 18 was triangulated with relevant information
      from tobacco industry reports, websites of British American Tobacco, Philip
      Morris International and ITGA, presentations by tobacco industry executives and
      internal industry documents from the Legacy Tobacco Documents Library website.
      RESULTS: Philip Morris International and British American Tobacco rejected
      Articles 9 and 10 draft Guidelines claiming that banning ingredients in
      cigarettes will render burley leaf less commercially viable making tobacco
      growers in many countries suffer economic consequences. They claimed the terms
      'attractiveness' and 'palatability' are not appropriate regulatory standards. The
      ITGA launched a global campaign to mobilise farmers to reject the draft
      Guidelines at COP4 in Uruguay. Tobacco producers, Brazil, Philippines, Tanzania,
      Zambia, Malawi and Zimbabwe, sent large delegations to COP4 and participated
      actively in the negotiation on the draft Guidelines. Partial Guidelines on
      Articles 9 and 10 on product regulation and disclosure were adopted. COP4's work
      on Article 17 provides guidance on viable alternatives, but the ITGA is opposed
      to this and continues fight crop substitution. CONCLUSION: Despite ITGA's
      international campaign to thwart the Guidelines on Articles 9 and 10 and a strong
      representation from tobacco-growing countries at COP4, the outcome after intense
      negotiations was the adoption of Partial Guidelines and work on Articles 17 and
      18 to proceed.

PMID- 22634570
TI  - The effect of tobacco control policies on smoking prevalence and smoking
      attributable deaths in Ireland using the IrelandSS simulation model.
AB  - OBJECTIVES: This study estimates the relative contribution of policies
      implemented between 1998 and 2010 to reductions in smoking prevalence by 2010. It
      then models the impact of implementing stronger policies, relative to a scenario
      of inaction, on smoking prevalence and smoking-attributable mortality in Ireland.
      METHODS: IrelandSS is an adapted version of SimSmoke, a dynamic simulation model
      used to examine the effect of tobacco control policies on smoking prevalence,
      through initiation and cessation, and associated future premature mortality.
      RESULTS: Model predictions for smoking prevalence are reasonably close to those
      from surveys. As a result of tobacco control policies implemented between 1998
      and 2010, there was a 22% relative reduction in smoking prevalence and 1716 fewer
      smoking-attributable deaths (SADs) by 2010 increasing to a 29% relative reduction
      in prevalence and 50 215 fewer SADs by 2040. With the introduction of stricter
      FCTC-compliant policies in 2011, the smoking prevalence can be decreased by as
      much as 13% initially, increasing to 28% by 30 years. With these stronger
      policies, a total of 24 768 SADs will be averted by 2040. CONCLUSIONS:
      Predictions from the IrelandSS model suggest that policies implemented between
      1998 and 2010 have had considerable effect; however, appreciable reductions in
      smoking prevalence and SADs can still be achieved through increasing taxes,
      maintaining a high-intensity tobacco control media campaign, introducing graphic
      health warnings and improving smoking cessation services.

PMID- 22634571
TI  - Patterns of snus and cigarette use: a study of Norwegian men followed from age 16
      to 19.
AB  - BACKGROUND: The use of moist snuff (snus) in young Norwegians is increasing,
      while smoking rates are declining. It is not clear whether snus facilitates
      smoking. OBJECTIVE: To assess whether 16-year-old men who were never-smokers, but
      snus users in 2001, had an increased risk of smoking 3 years later. METHODS: In a
      prospective school-based cohort study, 1440 men, who responded to questionnaires
      in 2001 and 2004, were included in the analyses. The participation rate was 89%
      in 2001 and 50% in 2004. Multinomial logistic regression models were used to
      assess the OR of snus users, smokers and dual users of cigarettes and snus,
      compared with non-tobacco users at baseline, to be smokers at follow-up. RESULTS:
      Snus use at baseline was associated with increased odds of dual use at follow-up
      when the outcome was (1) current dual use versus no tobacco (OR 3.49, 95% CI 1.8
      to 6.8) and when the outcome was (2) current dual use versus no smoking but
      including snus-only use (OR 1.88, 95% CI 1.1 to 3.3). Baseline snus users who
      were dual users at follow-up seemed to prefer using snus daily and cigarettes
      occasionally. Use of snus only at baseline was not associated with increased odds
      of smoking only at follow-up, after adjusting for known risk factors.
      CONCLUSIONS: Young men who only used snus at baseline had an increased risk of
      being dual users at follow-up. Snus use may therefore facilitate smoking.

PMID- 22634572
TI  - Receptivity to tobacco marketing and susceptibility to smoking among non-smoking
      male students in an urban setting in Lao PDR.
AB  - BACKGROUND: Tobacco marketing is a contributing factor to adolescent smoking, and
      now targeting adolescents in low- and middle-income countries. Especially,
      promotional items with tobacco brand logos have a great impact on adolescent
      smoking. OBJECTIVE: The authors evaluated whether receptivity to tobacco
      marketing is associated with susceptibility to smoking among non-smoking male
      students in Lao PDR. METHODS: The authors conducted a cross-sectional study with
      self-administered questionnaires among 526 non-smoking male students in grades
      8th and 11th (aged 12-19 years) in Vientiane Capital, Lao PDR. The authors
      investigated receptivity to tobacco marketing by three measurements: awareness of
      tobacco marketing, recognition of tobacco marketing messages and owning/being
      willing to use promotional items. The authors then conducted multiple logistic
      regression analysis to determine whether marketing receptivity had an independent
      association with smoking susceptibility, which is defined as the absence of a
      firm decision not to smoke. RESULTS: About 20% of the participants were
      susceptible to smoking. Recognition of marketing messages was significantly
      associated with susceptibility to smoking (OR=1.76, 95% CI 1.01 to 3.08), as was
      any owning/being willing to use promotional items with recognition of marketing
      messages (OR=2.39, 95% CI 1.34 to 4.24). In contrast, any owning/being willing to
      use promotional items without any recognition of marketing messages was not
      significantly associated with susceptibility. CONCLUSIONS: A significant
      association was detected between smoking susceptibility and marketing
      receptivity, which has been little explored in previous research in low-income
      countries. Owning/being willing to use promotional items was associated with
      smoking susceptibility only when there is also recognition of marketing messages.

PMID- 22634573
TI  - Enhanced memory ability: Insights from synaesthesia.
AB  - People with synaesthesia show an enhanced memory relative to demographically
      matched controls. The most obvious explanation for this is that the 'extra'
      perceptual experiences lead to richer encoding and retrieval opportunities of
      stimuli which induce synaesthesia (typically verbal stimuli). Although there is
      some evidence for this, it is unlikely to be the whole explanation. For instance,
      not all stimuli which trigger synaesthesia are better remembered (e.g., digit
      span) and some stimuli which do not trigger synaesthesia are better remembered.
      In fact, synaesthetes tend to have better visual memory than verbal memory. We
      suggest that enhanced memory in synaesthesia is linked to wider changes in
      cognitive systems at the interface of perception and memory and link this to
      recent findings in the neuroscience of memory.

PMID- 22634574
TI  - A rapid multiplex PCR assay that can reliably discriminate the cytochrome P450
      2D6 whole-gene deletion allele from 2D6*10 alleles.
AB  - BACKGROUND: Genetic polymorphisms of the human CYP2D6 gene can affect the
      metabolism of many drugs in clinical use. As a first step toward identifying poor
      drug metabolizers in the clinical setting, we developed a new multiplex PCR-based
      genotyping method to detect CYP2D6 whole-gene deletion. METHODS: We validated the
      new method by analyzing 500 genomic DNA samples from a Japanese population with
      the conventional long-PCR method and the new multiplex PCR method. The long-PCR
      system used a forward primer for CYP2D7P (a pseudogene closely related to CYP2D6)
      and a common reverse primer for the untranslated region. The multiplex PCR system
      used the same two primers as the long PCR and an additional forward primer for
      CYP2D6. RESULTS: With the long-PCR system, DNA samples identified as containing
      CYP2D6*5 (whole-gene deletion) formed 3.5-kb PCR products. With the multiplex PCR
      system, many samples yielded 4.7-kb PCR products (implying the existence of
      normal CYP2D6) and some DNA samples yielded 6.2-kb PCR products (probably
      indicating CYP2D6*10D). The long-PCR assay detected 64 CYP2D6*5 alleles among
      1000 Japanese alleles; however, the new multiplex PCR system identified 5 of
      these 64 alleles as CYP2D6*10D. CONCLUSIONS: The new multiplex PCR method is
      useful for detecting CYP2D6*5. This system could reliably discriminate CYP2D6*5
      from homologous pseudogene CYP2D7P and functional CYP2D6*10D.

PMID- 22634575
TI  - desat1: A Swiss army knife for pheromonal communication and reproduction?
AB  - The desat1 gene possesses an extraordinary-maybe unique-feature in the control of
      sensory communication systems: it codes for the two principal and complementary
      aspects-the emission and the reception-of Drosophila sex pheromones. These two
      complex aspects depend on separate genetic control indicating that desat1
      pleiotropically acts on pheromonal communication. This gene also control other
      characters either related to reproduction and to osmoregulation. Such a
      functional pleiotropy may be related to the molecular structure of desat1 gene
      which combines a highly conserved coding region with fast evolving regulatory
      regions: It produces at least five transcripts all giving rise to the ?9
      desaturase enzyme.

PMID- 22634576
TI  - Remodeling of synapses in the CA1 area of the hippocampus after transient global
      ischemia.
AB  - Synapses are essential to neuronal functions. Synaptic changes occur under
      physiological and pathological conditions. Here we report the remodeling of
      synapses in the CA1 area of the hippocampus after transient global ischemia using
      electron microscopy. Much electron-dense material appeared in the cytoplasm of
      dendrites at 24h after ischemia. Many dark axons or terminals were found in the
      CA1 neuropil; some of which were phagocytized by dendrites. Interestingly
      autophagosomes appeared in many axons or dendrites at 48 h after ischemia. In
      addition, postsynaptic density (PSD) - like structures or synaptic - like
      structures were found inside spines and dendrites. Statistical analysis
      demonstrated that the thickness of PSDs in the CA1 neuropil increased from 12 to
      48 h after ischemia. The frequency of autophagosomes appeared to escalate from 12
      to 48 h after ischemia. The frequency of asymmetric synapses was significantly
      increased at 12h and 24h after ischemia in stratum oriens, proximal and distal
      stratum radiatum. Among asymmetric synapses, the number of perforated synapses
      consistently increased and reached a peak (approximately 10-fold increase) at 48
      h after ischemia. On the other hand, the number of multiple synaptic boutons
      decreased after ischemia reaching a two to fourfold decrease at 48 h after
      ischemia. These results have shown that ischemia induces an increase of
      asymmetric synapses as well as synaptic autophagy, which may contribute to the
      neuronal death in the CA1 area after transient global ischemia.

PMID- 22634577
TI  - Antisense oligonucleotides for the treatment of dyslipidaemia.
AB  - Antisense oligonucleotides (ASOs) are short synthetic analogues of natural
      nucleic acids designed to specifically bind to a target messenger RNA (mRNA) by
      Watson-Crick hybridization, inducing selective degradation of the mRNA or
      prohibiting translation of the selected mRNA into protein. Antisense technology
      has the ability to inhibit unique targets with high specificity and can be used
      to inhibit synthesis of a wide range of proteins that could influence lipoprotein
      levels and other targets. A number of different classes of antisense agents are
      under development. To date, mipomersen, a 2'-O-methoxyethyl phosphorothioate 20
      mer ASO, is the most advanced ASO in clinical development. It is a second
      generation ASO developed to inhibit the synthesis of apolipoprotein B (apoB)-100
      in the liver. In Phase 3 clinical trials, mipomersen has been shown to
      significantly reduce plasma low-density lipoprotein cholesterol (LDL-c) as well
      as other atherogenic apoB containing lipoproteins such as lipoprotein (a) [Lp(a)]
      and small-dense LDL particles. Although concerns have been raised because of an
      increase in intrahepatic triglyceride content, preliminary data from long-term
      studies suggest that with continued treatment, liver fat levels tend to stabilize
      or decline. Further studies are needed to evaluate potential clinical relevance
      of these changes. Proprotein convertase subtilisin/kexin-9 (PCSK9) is another
      promising novel target for lowering LDL-c by ASOs. Both second-generation ASOs
      and ASOs using locked nucleic acid technology have been developed to inhibit
      PCSK9 and are under clinical development. Other targets currently being addressed
      include apoC-III and apo(a) or Lp(a). By directly inhibiting the synthesis of
      specific proteins, ASO technology offers a promising new approach to influence
      the metabolism of lipids and to control lipoprotein levels. Its application to a
      wide variety of potential targets can be expected if these agents prove to be
      clinically safe and effective.

PMID- 22634578
TI  - Biologically active steroids from the aerial parts of Vernonia anthelmintica
      Willd.
AB  - A new steroid, vernoanthelsterone A (1), and five known steroids were isolated
      from the aerial parts of Vernonia anthelmintica Willd. Compound 1 possesses a
      Delta(8(14))-15-one moiety. To our best knowledge, few steroids with this moiety
      have been reported before. Compounds 1-6 were tested for their antibacterial
      activities and their effects on estrogen biosynthesis in human ovarian granulosa
      like cells (KGN cells). Compound 2 showed the ability to promote estrogen
      biosynthesis with EC(50) of 56.95 MUg/mL and also exhibited the antibacterial
      activities against Bacillus cereus, Staphyloccocus aureus, Bacillus subtilis and
      Escherichia coli with MICs ranging from 3.15 to 15.5 MUg/mL. The structures of 1
      6 were determined on the basis of IR, MS, 1D and 2D NMR.

PMID- 22634580
TI  - Protective effects of an extract from Citrus bergamia against inflammatory injury
      in interferon-gamma and histamine exposed human keratinocytes.
AB  - AIMS: The present work evaluated the anti-inflammatory/antioxidant activity of a
      well characterized extract from Citrus bergamia Risso and Poiteau (CBE),
      containing neoeriocitrin, naringin, neohesperidin and other flavonoids, on human
      NCTC 2544 keratinocytes treated with interferon-gamma (IFN-gamma) and histamine
      (H). MAIN METHODS: High performance liquid chromatography (HPLC) coupled with
      diode array detectors was used to characterize and quantify phenolic compounds in
      CBE. Anti-inflammatory/antioxidant ability on keratinocytes was determined
      through evaluation of inter-cellular adhesion molecule-1 (ICAM-1) and inducible
      nitric oxide synthase (iNOS) expression by Western blot, production of nitric
      oxide (NO) with Griess reagent and concentration of reactive oxygen species (ROS)
      by fluorescent quantitative analysis with 2',7'-dichlorfluorescein-diacetate
      (DCFH-DA). Cell viability was assessed using 3-(4,5-dimethyl-2 thiazoyl)-2,5
      diphenyl-2H-tetrazolium bromide (MTT) assay. Antioxidant activity was also
      measured by oxygen radical absorbance capacity (ORAC) assay. Glycosaminoglycans
      (GAGs) were quantified using 1.9-dimethyl methylene blue (DMB). KEY FINDINGS: CBE
      exhibited high antioxidant activity confirmed by elevated ORAC values related to
      high capacity in oxygen radical scavenging. The assays on keratinocytes
      demonstrated that CBE does not inhibit cell proliferation and is shown to
      significantly reduce dose-dependently ICAM-1, iNOS, NO, ROS and GAG production in
      cells exposed to IFN-gamma and H. SIGNIFICANCE: Our study demonstrates that the
      pools of compounds of an extract from C. bergamia efficiently block the
      proinflammatory actions induced by IFN-gamma and H on human keratinocytes. CBE
      may be used for topic employment in some inflammatory diseases of the skin and to
      represent an important opportunity for the essential oil processing industries.

PMID- 22634579
TI  - Inactivation of PI3K/Akt signaling mediates proliferation inhibition and G2/M
      phase arrest induced by andrographolide in human glioblastoma cells.
AB  - AIMS: Andrographolide, a principal diterpenoid lactone isolated from the
      traditional herbal medicine Andrographis paniculata, has been reported to show
      anti-tumor activity. Since the high lipid solubility of andrographolide permits
      it to penetrate the blood-brain barrier and concentrate in the brain, we
      hypothesized that andrographolide may be a potential chemotherapeutic agent for
      the treatment of glioblastomas. To clarify this point, we investigated the growth
      inhibitory effect and mechanisms of actions of andrographolide on human
      glioblastoma U251 and U87 cells. MAIN METHODS: MTT assay and trypan blue
      exclusion assay were used to investigate the proliferation inhibitory and
      cytotoxic effects of andrographolide, respectively. Cell cycle distribution was
      analyzed using flow cytometry. Apoptosis analysis proceeded by detecting the
      cleavage of caspase-3. The levels of proteins were probed by Western blotting.
      KEY FINDINGS: The results showed that non-toxic concentrations of andrographolide
      inhibited the proliferation of human glioblastoma cells through induction of G2/M
      arrest, which was accompanied by down-regulating Cdk1 and Cdc25C proteins.
      Additionally, andrographolide decreased the activity of PI3K/Akt signaling, as
      demonstrated by down-regulation of the expression of phos-PI3K, phos-Akt, phos
      mTOR and phos-p70s6k in U251 and U87 cells. Furthermore, additive effects on the
      proliferation inhibition, G2/M arrest and down-regulation of G2/M phase-related
      proteins were observed, when a combined treatment of andrographolide with PI3K
      inhibitor LY294002 was used in U251 and U87 cells. SIGNIFICANCE: We prove that
      andrographolide inhibits the proliferation of human glioblastoma cells via
      inducing G2/M arrest, which is mediated by inhibiting the activity of PI3K/Akt
      signaling.

PMID- 22634581
TI  - Hydroxyxanthone as an inhibitor of cAMP-activated apical chloride channel in
      human intestinal epithelial cell.
AB  - AIMS: Previous investigation showed that polyphenols abundantly found in many
      plants could inhibit Cl(-) secretion. The present study was aimed to investigate
      the effect of phenol containing xanthone derivatives on cAMP-activated intestinal
      Cl(-) secretion and evaluate potential benefits of these compounds in the
      treatment of cholera. MAIN METHODS: Four hydroxy xanthones were synthesized via
      oxidative coupling reaction of the corresponding ortho-hydroxybenzoic acids and
      hydroxyphenols. Short-circuit current and apical Cl(-) current measurements
      across monolayers of human intestinal epithelial (T84) cell and Fisher rat
      thyroid cells transfected with human CFTR (FRT-hCFTR cell) were performed to
      determine the effect of hydroxyxanthones on cAMP-activated Cl(-) secretion.
      Intracellular cAMP was measured by immunoassay methods. Anti-diarrheal efficacy
      was evaluated using closed loop model of cholera. KEY FINDINGS: Among the tested
      xanthones, 1,3,6-trihydroxyxanthone (THX-001) was found to be the most potent
      derivative in the inhibition of cAMP-activated Cl(-) secretion across T84 cell
      monolayers (IC(50)~100MUM). Electrophysiological analysis of T84 cells and FRT
      hCFTR cells revealed that THX-001 targeted two distinct cAMP-activated Cl(-)
      channels in the apical membrane of T84 cells, namely, CFTR and inward rectifying
      Cl(-) channel (IRC). In contrast, THX-001 had no effect on intracellular cAMP
      levels in these cells. Importantly, THX-001 completely abolished cholera toxin
      induced Cl(-) secretion across T84 cell monolayers and significantly inhibited
      cholera toxin-induced intestinal fluid secretion in mouse closed loop models.
      SIGNIFICANCE: This study revealed that hydroxyxanthone represents another
      chemical class of polyphenolic compounds that may hold promise as anti-secretory
      therapy for cholera.

PMID- 22634582
TI  - Efficient iodine-free dye-sensitized solar cells employing truxene-based organic
      dyes.
AB  - Two new truxene-based organic sensitizers (M15 and M16) featuring high extinction
      coefficients were synthesized for dye-sensitized solar cells employing cobalt
      electrolyte. The M16-sensitized device displays a 7.6% efficiency at an
      irradiation of AM1.5 full sunlight.

PMID- 22634583
TI  - Phonon-lifetimes in demixing systems.
AB  - The dynamics of silver-alkali halide mixed single crystals (Ag(x)Na(1-x)Br, x =
      0.23, 0.35, 0.40 and 0.70) were studied by inelastic neutron scattering during
      the process of spinodal decomposition. Using the thermal three-axes spectrometer
      PUMA as well as the time-of-flight spectrometer IN5, the time evolution of
      phonons was observed in time-resolved, stroboscopic measurements. Complementary
      to the study of long wavelength acoustic phonons, as studied previously, we
      extended these investigations to Brillouin-zone boundary modes that are
      particularly sensitive to variations of the local structure. Starting from the
      homogeneous mixed phase the behaviour of these modes during demixing is observed
      in real-time. A simple dynamical model based on local structure variants helps to
      interpret the results. It is shown that the phonon lifetimes vary strongly during
      the phase separation and increase drastically during the coarsening process. Up
      to a critical size of precipitates of about 10 nm, zone-boundary modes are found
      to be strongly damped, while beyond the line widths are reduced to the
      experimental resolution. This finding leads to the conclusion that the typical
      mean free path of these modes is of the order of 10 nm, which corresponds to 20
      unit cells.

PMID- 22634585
TI  - Something old, something new.

PMID- 22634584
TI  - Suicide gene therapy in cancer: where do we stand now?
AB  - Suicide gene therapy is based on the introduction into tumor cells of a viral or
      a bacterial gene, which allows the conversion of a non-toxic compound into a
      lethal drug. Although suicide gene therapy has been successfully used in a large
      number of in vitro and in vivo studies, its application to cancer patients has
      not reached the desirable clinical significance. However, recent reports on pre
      clinical cancer models demonstrate the huge potential of this strategy when used
      in combination with new therapeutic approaches. In this review, we summarize the
      different suicide gene systems and gene delivery vectors addressed to cancer,
      with particular emphasis on recently developed systems and associated bystander
      effects. In addition, we review the different strategies that have been used in
      combination with suicide gene therapy and provide some insights into the future
      directions of this approach, particularly towards cancer stem cell eradication.

PMID- 22634586
TI  - Fast-dissolving and high-drug-loaded, Fatty Acid-based self-emulsifying solid
      dispersions of diacerein.
AB  - The purpose of the present study was to enhance the solubility and dissolution of
      diacerein by preparing their fatty acid-based, self-emulsifying solid dispersions
      (SDs) containing polyethylene glycol 6000 (PEG 6000), surfactant, and self
      emulsifying excipient with high drug content. Ternary and self-emulsifying SDs
      containing high drug content were prepared and characterized by powder X-ray
      diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform
      infrared spectroscopy, solubility studies, and dissolution studies. When
      hydrophilic and lipophilic excipients were combined and incorporated into PEG
      6000-based SDs, a remarkable enhancement of the dissolution rate was observed,
      even in SDs with high drug content. The presence of surfactant and self
      emulsifying excipient did not affect the solid state characterization of the
      drug. The decrease in the intensity of the numerous distinctive peaks of the drug
      in the PXRD spectra and absence of drug melting peak in DSC spectra demonstrated
      that a high concentration of the drug molecules was dissolved in the solid-state
      carrier matrix. The utilization of self-emulsifying excipient and surfactant in
      PEG 6000-based SDs could be a useful tool to enhance the dissolution and
      bioavailability of diacerein by forming solubilizing and microemulsifying systems
      with high drug content. LAY ABSTRACT: The purpose of the present study was to
      enhance the solubility and dissolution of diacerein by preparing their fatty acid
      based, self-emulsifying solid dispersions with high drug content. These solid
      dispersions were prepared and characterized by powder X-ray diffraction,
      differential scanning calorimetry, Fourier transform infrared spectroscopy,
      solubility studies, and dissolution studies. When hydrophilic and lipophilic
      excipients were combined and incorporated into PEG 6000-based solid dispersions,
      a remarkable enhancement of the dissolution rate was observed, even in solid
      dispersions with high drug content. Moreover, the presence of surfactant and self
      emulsifying excipient did not affect the solid state characterization of the
      drug. The decrease in the intensity of the numerous distinctive peaks of the drug
      in the powder X-ray diffraction spectra and absence of drug melting peak in the
      spectra obtained by differential scanning calorimetry demonstrated that a high
      concentration of the drug molecules was dissolved in the solid-state carrier
      matrix.

PMID- 22634587
TI  - Alumina Depyrogenates F 18 Fludeoxyglucose Injection during Purification
      Processes.
AB  - Endotoxin indicators (EIs) and photometric bacterial endotoxin test (BET) assays
      were used to determine the capacity of alumina (Al(2)O(3)) for removing endotoxin
      from a parenteral solution. Fludeoxyglucose F 18 (FDG) Injection, USP, a
      radioactive imaging agent, is made daily at about 150 American sites for same-day
      administration. Each FDG synthesis unit contains a cartridge of alumina for
      removing a radiochemical impurity before delivery to the final product vial.
      Recognizing that alumina is a cationic adsorption medium, its capacity for
      removing endotoxin was challenged with purified endotoxin. A 2000 EU vial of an
      EI was reconstituted with water or FDG, vortex-mixed, and passed through a
      representative final product assembly consisting of an alumina cartridge with
      connecting tubing, a sterilizing membrane filter, and aseptic collection vial. In
      addition to sterilization, the filter removed alumina "fines" that are inhibitory
      to the BET because of adsorption of the positive control. Confirmation of labeled
      claim for each EI and measurement of endotoxin challenge eluates from a simulated
      FDG process were analyzed by valid kinetic chromogenic assays using a microplate
      reader and a cartridge reader. Overkill depyrogenation conditions were achieved,
      defined as greater than a 3 log endotoxin reduction. In conclusion, alumina was
      observed to depyrogenate the eluate of a representative FDG synthesis unit. LAY
      ABSTRACT: A fever-inducing (pyrogenic) bacterial toxin may arise during the
      complex synthesis of a radioactive imaging agent known as Fludeoxyglucose F 18
      (FDG) Injection. One of the purification steps for FDG, a cartridge of aluminum
      oxide (alumina), removes negatively charged, radioactive impurities.
      Representative FDG solutions were inoculated with purified bacterial endotoxin to
      determine if the toxin's negative charge would result in removal by alumina.
      Alumina's effectiveness for endotoxin removal, a process known as depyrogenation,
      was measured by endotoxin detection assays. Alumina reduced endotoxin levels by
      more than a thousand fold in a simulated FDG process. Therefore, an unrecognized
      benefit of the alumina cartridge is removal of a potentially harmful toxin while
      purifying the FDG for patient injection.

PMID- 22634588
TI  - Investigation of freeze/thaw-related quality attributes of a liquid
      biopharmaceutical formulation: the role of saccharide excipients.
AB  - Saccharides, including sucrose, trehalose, mannitol, and sorbitol, are commonly
      employed as stabilizers, cryoprotectants, and/or tonicity adjusters in protein
      formulations. During the thawing of a protein-containing formulated bulk drug
      substance conducted prior to a drug product (DP) filling operation, a white,
      crystalline precipitate was observed. In addition, upon thawing, vial breakage
      was observed for filled DP that had been previously frozen at -40  degrees C. To
      investigate the causes of both phenomena, the freeze/thaw behavior of the
      formulation components was studied. Multiple physical characterization
      techniques, including differential scanning calorimetry (DSC), electrical
      resistance measurements, thermomechanical analysis (TMA), and powder X-ray
      diffraction (PXRD), were utilized to characterize the formulations. The PXRD
      pattern of precipitate collected from thawed bulk was consistent with that of a
      mannitol control. An exothermic transition observed by DSC, a sharp increase in
      electrical resistance detected via resistivity measurements, and the onset of
      volumetric expansion of the frozen matrix evident in the TMA curve offer evidence
      that the frozen mannitol solution undergoes transitions at or near the vial
      breakage temperature (-22 to -23  degrees C) observed during warming. In
      addition, osmolality measurements taken from fractionated aliquots of frozen
      samples indicated that non-uniform concentration gradients contributed to
      precipitation of mannitol observed at larger scales. Small-scale laboratory
      experiments (i.e., 10-125 mL) failed to adequately predict behavior at larger
      scale (i.e., in 1 L and 2 L bottles). Upon linking the detrimental behavior to
      the freeze/thaw properties of the tonicity adjustor, mannitol, alternative
      saccharide excipients, including sorbitol, sucrose, and trehalose, were evaluated
      at isotonic concentrations over a temperature range of -80 to 25  degrees C using
      physical-chemical techniques and visual observation. Neither precipitation nor
      vial breakage was observed for the alternate saccharides. Recommendations for
      saccharide selection are provided based on storage conditions and scale
      considerations for liquid biopharmaceutical formulations. LAY ABSTRACT:
      Saccharides, including sucrose, trehalose, mannitol, and sorbitol, are commonly
      employed as stabilizers, cryoprotectants and/or tonicity adjusters in protein
      formulations. During thawing of formulated bulk drug substance, a white,
      crystalline precipitate was observed. In addition, upon thawing, vial breakage
      was observed for filled drug product that had been previously frozen at -40 
      degrees C. To investigate the causes of both phenomena, multiple physical
      characterization techniques were utilized to characterize the formulations. The
      powder X-ray diffraction pattern of precipitate collected from thawed bulk was
      consistent with that of a mannitol control. Upon linking the detrimental behavior
      to the freeze/thaw properties of the tonicity adjustor, mannitol, alternative
      saccharide excipients, including sorbitol, sucrose, and trehalose, were evaluated
      at isotonic concentrations over a temperature range of -80 to 25  degrees C using
      physico-chemical techniques and visual observation. Neither precipitation nor
      vial breakage was observed for the alternate saccharides. Recommendations for
      saccharide selection are given based on storage conditions and scale
      considerations for liquid biopharmaceutical formulations.

PMID- 22634589
TI  - In vitro Antifungal Efficacy of Biguanides and Quaternary Ammonium Compounds
      against Cleanroom Fungal Isolates.
AB  - In vitro antifungal activities of three biocides including one biguanide
      (chlorhexidine) and two quaternary ammonium compounds (benzalkonium chloride and
      cetrimide) were studied against eight cleanroom fungal isolates by using a
      microbiological broth dilution technique as per Clinical and Laboratory Standards
      Institute (CLSI) M38-A guidelines. No data exists on the activity of biocides on
      pharmaceutical cleanroom fungal isolates. Minimum inhibitory concentrations
      (MICs) for all three biocides against species of Aspergillus and Penicillium
      species ranged between 4 and 16 MUg/mL. MICs of Curvularia, Cladosporium, and
      Alternaria species also showed less than 16 MUg/mL. To date, susceptibility
      breakpoints have not been established for biocides, and this is the first study
      using the CLSI broth microdilution antifungal susceptibility testing to determine
      the MIC value of biocides. This study clearly demonstrates that the most
      frequently isolated micro-organisms from an environmental monitoring program may
      be periodically subjected to microbroth dilution testing with cleanroom
      disinfectant agents used in the disinfection program to confirm their sensitivity
      profile. Further work is needed in this field to increase our understanding of
      biocides against different fungal isolates and to enable to the design of more
      efficient disinfection and contamination control programs. LAY ABSTRACT:
      Increased trend of fungal growth is observed in pharmaceutical and medical device
      cleanrooms. It is essential to have knowledge of choosing effective disinfectants
      for minimizing fungal occurrence in cleanrooms. The present study establish
      minimum cut-offs for specific fungal isolates that are problematic in cleanrooms
      against commonly used disinfectants (quaternary ammonium compounds and
      biguanides). Further studies based on this minimum inhibitory concentration of
      disinfectants, effective time, and cleaning methods could prevent fungal
      occurrence.

PMID- 22634590
TI  - Quality Risk Management: Putting GMP Controls First.
AB  - This paper presents a practical way in which current approaches to quality risk
      management (QRM) may be improved, such that they better support qualification,
      validation programs, and change control proposals at manufacturing sites. The
      paper is focused on the treatment of good manufacturing practice (GMP) controls
      during QRM exercises. It specifically addresses why it is important to evaluate
      and classify such controls in terms of how they affect the severity, probability
      of occurrence, and detection ratings that may be assigned to potential failure
      modes or negative events. It also presents a QRM process that is designed to
      directly link the outputs of risk assessments and risk control activities with
      qualification and validation protocols in the GMP environment. LAY ABSTRACT: This
      paper concerns the need for improvement in the use of risk-based principles and
      tools when working to ensure that the manufacturing processes used to produce
      medicines, and their related equipment, are appropriate. Manufacturing processes
      need to be validated (or proven) to demonstrate that they can produce a medicine
      of the required quality. The items of equipment used in such processes need to be
      qualified, in order to prove that they are fit for their intended use. Quality
      risk management (QRM) tools can be used to support such qualification and
      validation activities, but their use should be science-based and subject to as
      little subjectivity and uncertainty as possible. When changes are proposed to
      manufacturing processes, equipment, or related activities, they also need careful
      evaluation to ensure that any risks present are managed effectively. This paper
      presents a practical approach to how QRM may be improved so that it better
      supports qualification, validation programs, and change control proposals in a
      more scientific way. This improved approach is based on the treatment of what are
      called good manufacturing process (GMP) controls during those QRM exercises. A
      GMP control can be considered to be any control that is put in place to assure
      product quality and regulatory compliance. This improved approach is also based
      on how the detectability of risks is assessed. This is important because when
      producing medicines, it is not always good practice to place a high reliance upon
      detection-type controls in the absence of an adequate level of assurance in the
      manufacturing process that leads to the finished medicine.

PMID- 22634591
TI  - Implementation of parallelism testing for four-parameter logistic model in
      bioassays.
AB  - Parallelism is a prerequisite for the determination of relative potency in
      bioactivity assays. It involves the testing of similarity between a pair of dose
      response curves of reference standard and test sample. The evaluation of
      parallelism is a requirement listed by both the United States Pharmacopeia (USP)
      and European Pharmacopeia (EP). The revised USP Chapters <1032> and <1034>
      suggest testing parallelism using an equivalence method. However, implementation
      of this method can be challenging for laboratories that lack experience in
      statistical analysis and software development. In this paper we present a
      customized assay analysis template that is developed based on a fully good
      manufacturing practice (GMP)-compliant software package. The template allows for
      automation of the USP-recommended equivalence parallelism testing method for
      4PLmodel in bioassays. It makes the implementation of the USP guidance both
      practical and feasible. Use of the analysis template is illustrated through a
      practical example. LAY ABSTRACT: Parallelism is a prerequisite for the
      determination of relative potency in bioactivity assays. It involves the testing
      of similarity between a pair of dose-response curves of reference standard and
      test sample. The evaluation of parallelism is a requirement listed by both the
      United States Pharmacopeia (USP) and European Pharmacopeia (EP). The revised USP
      Chapters <1032> and <1034> suggest testing parallelism using an equivalence
      method. However, implementation of this method can be challenging for
      laboratories that lack experience in statistical analysis and software
      development. In this paper we present a customized assay analysis template that
      is developed based on a fully good manufacturing practice (GMP)-compliant
      software package. The template allows for automation of the USP-recommended
      equivalence parallelism testing method for 4-parameter logistic model in
      bioassays. It makes the implementation of the USP guidance both practical and
      feasible. Use of the analysis template is illustrated through a practical
      example.

PMID- 22634592
TI  - Reliable drug quality: an unresolved problem.

PMID- 22634593
TI  - Considerations for design and use of container challenge sets for qualification
      and validation of visible particulate inspection.
AB  - The major compendia require sterile injectable and ophthalmic drugs, to be
      prepared in a manner that is designed to exclude particulate matter. This
      requirement is satisfied by testing for subvisual particles in the laboratory and
      100% inspection of all containers for the presence of visible particles.
      Inspection for visible particles is performed in the operations area using one of
      three methods. Manual inspection is based on human visual acuity, the ability of
      the inspector to discern between conforming and nonconforming containers, and the
      ability to remove nonconforming units. Semi-automated inspection is a variation
      of manual inspection, in which a roller conveyor handles and presents the
      containers to the human inspector. Fully automated inspection systems perform
      handling, inspection, and rejection of defective containers. All inspection
      methods must meet the compendial requirement for sterile drug product to be
      "essentially free" of visible particulates. Given the random occurrence of
      particles within the batch, visual detection of a particle in an individual
      container is probabilistic. The probability of detection for a specific particle
      is affected by many variables that include product attributes, container size and
      shape, particle composition and size, and inspection capability. The challenge
      set is a useful tool to assess the particle detection in a product, and it may
      also be used to evaluate detection of container/closure defects. While the
      importance of a well-designed challenge set is not always recognized or
      understood, it serves as the cornerstone for qualification and/or validation of
      all inspection methods. This article is intended to provide useful information
      for the design, composition, and use of container challenge sets for particulate
      inspection studies. LAY ABSTRACT: Regulations require drug products intended for
      injection or ophthalmic use to be sterile and free of particles that could harm
      the patient. This requirement is meet by 100% inspection of every drug container
      in the lot and the removal of any defective unit before it is released for
      patient use. Great progress has been made through the creation of a harmonized
      method for the detection of small particles in drug product and universal
      recognition of container defects. Differing opinions concerning the conduct of
      large particle inspection have hindered the creation of a harmonized method. The
      absence of a standard method has created confusion that must be resolved for
      acceptance of drug products in the global marketplace. While the importance of a
      well-designed test set for qualification of these methods is overlooked or
      misunderstood, it can serve as the cornerstone for qualification of all
      inspection methods. This article is intended to provide valuable information for
      test sets used qualify inspection systems. The proper design and use of these
      test sets will provide clarity for inspection qualification, which can be applied
      to the inspection of commercial product.

PMID- 22634596
TI  - Postexposure prophylaxis for influenza in pediatric wards oseltamivir or
      zanamivir after rapid antigen detection.
AB  - BACKGROUND: Postexposure prophylaxis (PEP) using neuraminidase inhibitors against
      exposure to influenza virus has been well studied in household settings but not
      in nosocomial settings in pediatric wards. METHODS: We used oseltamivir or
      zanamivir as PEP in our pediatric wards. All influenza cases were diagnosed by
      the influenza rapid diagnostic test. RESULTS: Between 2003 and 2011, there were
      20 nosocomial introductions of influenza (10 were A, 9 were B and 1 was
      undetermined). The index cases consisted of 17 inpatients, 2 parents and 1
      medical staff member. The 17 inpatients had been admitted to the hospital for
      reasons other than infectious disease and they developed influenza after
      hospitalization. Among the 81 contacts, 28 (35%) were exposed to influenza A, and
      52 (64%) were exposed to influenza B. The rate of secondary infection among
      contacts not given PEP was 29% (5/17), and the rate among contacts given PEP was
      significantly lower, 3% (2/63; P = 0.004). The 2 infected contacts who had been
      given PEP were both influenza B cases, and both had received oseltamivir. The
      contacts who received PEP within 24 hours (59), for influenza A (23) and those
      who received zanamivir (15) did not develop influenza. No adverse events were
      reported. CONCLUSIONS: PEP using oseltamivir or zanamivir for unexpected
      occurrences of nosocomial influenza in pediatric wards is safe and effective. The
      influenza rapid diagnostic test that we used was helpful for detecting nosocomial
      influenza in children.

PMID- 22634597
TI  - Evidence of multiple introductions of HIV-1 subtype C in Angola.
AB  - HIV-1 subtype C is the most prevalent group M clade in southern Africa and some
      eastern African countries. Subtype C is also the most frequent subtype in Angola
      (southwestern Africa), with an estimated prevalence of 10-20%. In order to better
      understand the origin of the HIV-1 subtype C strains circulating in Angola, 31
      subtype C pol sequences of Angolan origin were compared with 1950 subtype C pol
      sequences sampled in other African countries. Phylogenetic analyses reveal that
      the Angolan subtype C sequences were distributed in 16 different lineages that
      were widely dispersed among other African strains. Ten subtype C Angolan lineages
      were composed by only one sequence, while the remaining six clades contain
      between two and seven sequences. Bayesian phylogeographic analysis indicates that
      most Angolan clades probably originated in different southern African countries
      with the exception of one lineage that most likely originated in Burundi.
      Evolutionary analysis suggests that those Angolan subtype C clades composed by >=
      2 sequences were introduced into the country between the late 1970s and the mid
      2000s. The median estimated time frame for the origin of those Angolan lineages
      coincides with periods of positive migration influx in Angola that were preceded
      by phases of negative migratory outflow. These results demonstrate that the
      Angolan subtype C epidemic resulted from multiple introductions of subtype C
      viruses mainly imported from southern African countries over the last 30years,
      some of which have been locally disseminated establishing several autochthonous
      transmission networks. This study also suggests that population mobility between
      Angola and southern African countries during civil war (1974-2002) may have
      played a key role in the emergence of the Angolan subtype C epidemic.

PMID- 22634598
TI  - Isolation and characterization of a mannose-binding insecticidal lectin gene from
      Allium sativum (garlic) and its putative role in insect resistance using
      bioinformatics tools.
AB  - Monocot mannose-binding lectins (MMBLs) or agglutinins are an extended
      superfamily of structurally and evolutionarily related proteins. They play
      important roles in plant defenses. Here we describe the synthesis of full-length
      cDNA of monocot mannose-binding insecticidal agglutinin isolated from Allium
      sativum, a traditional herb known to be of great applications in Africa, using
      reverse transcription polymerase chain reaction (RT-PCR) with specific primers
      designed based on the insecticidal sequence (NCBI primary accession no.
      AY866499.1). Sequence analysis revealed a 327bp open reading frame (ORF) encoding
      a putative 108-aa agglutinin precursor with a C-terminal domain. Multiple
      alignments of BLEC1 amino acids with those of eight other MMBLs revealed three
      highly conserved domains among them, indicating BLEC1 belongs to a member of the
      MMBL superfamily. Tertiary structure analysis showed that BLEC1 had three
      potential equal mannose-binding sites. Phylogenetic analysis indicated that 20
      MMBLs including BLEC1 belonged to an extended superfamily. Gene ontology analyses
      indicate one biological process with GO ID: 0006952 representing defense
      response, with two secondary IDs GO: 0002217 GO: 0042829. The child terms has
      both negative and positive regulation some of which include GO: 0002242 defense
      response to parasitic plant and GO: 0002213 defense response to insect. The
      cloning and characterization of BLEC1 will enable us to study its potential use
      in plant genetic engineering in the development of insect resistance plant.

PMID- 22634595
TI  - Caenorhabditis elegans screen reveals role of PAR-5 in RAB-11-recycling endosome
      positioning and apicobasal cell polarity.
AB  - Apically enriched Rab11-positive recycling endosomes (Rab11-REs) are important
      for establishing and maintaining epithelial polarity. Yet, little is known about
      the molecules controlling trafficking of Rab11-REs in an epithelium in vivo.
      Here, we report a genome-wide, image-based RNA interference screen for regulators
      of Rab11-RE positioning and transport of an apical membrane protein (PEPT-1) in
      C. elegans intestine. Among the 356 screen hits was the 14-3-3 and partitioning
      defective protein PAR-5, which we found to be specifically required for Rab11-RE
      positioning and apicobasal polarity maintenance. Depletion of PAR-5 induced
      abnormal clustering of Rab11-REs to ectopic sites at the basolateral cortex
      containing F-actin and other apical domain components. This phenotype required
      key regulators of F-actin dynamics and polarity, such as Rho GTPases (RHO-1 and
      the Rac1 orthologue CED-10) and apical PAR proteins. Our data suggest that PAR-5
      acts as a regulatory hub for a polarity-maintaining network required for
      apicobasal asymmetry of F-actin and proper Rab11-RE positioning.

PMID- 22634599
TI  - Guidelines for the public health management of typhoid and paratyphoid in
      England: practice guidelines from the National Typhoid and Paratyphoid Reference
      Group.
AB  - OBJECTIVES: The Typhoid and Paratyphoid Reference Group (TPRG) was convened by
      the Health Protection Agency (HPA) and the Chartered Institute of Environmental
      Health (CIEH) to revise guidelines for public health management of enteric fever.
      This paper presents the new guidelines for England and their rationale. METHODS:
      Methods include literature reviews including grey literature such as audit data
      and case studies; analysis of enhanced surveillance data from England, Wales and
      Northern Ireland; review of clearance and screening schedules in use in other non
      endemic areas; and expert consensus. RESULTS: The evidence and principles
      underpinning the new guidance are summarised. Significant changes from previous
      guidance include: * Algorithms to guide risk assessment and management, based on
      risk group and travel history; * Outline of investigation of non-travel cases; *
      Simplified microbiological clearance schedules for cases and contacts; * Targeted
      co-traveller screening and a "warn and inform" approach for contacts; *
      Management of convalescent and chronic carriers. CONCLUSIONS: The guidelines were
      launched in February 2012. Feedback has been positive: the guidelines are
      reported to be clear, systematic, practical and risk-based. An evaluation of the
      guidelines is outlined and will add to the evidence base. There is potential for
      simplification and consistency between international guidelines.

PMID- 22634601
TI  - Reference intervals for reproductive hormones in prepubertal children on the
      automated Roche cobas e 411 analyzer.
AB  - OBJECTIVES: To establish reference intervals for luteinizing hormone (LH),
      follicle-stimulating hormone (FSH), estradiol (E2), progesterone (P), total and
      free testosterone (T) and sex-hormone binding globulin (SHBG) in prepubertal
      children and to assess age- and gender-related differences. DESIGN AND METHODS: A
      total of 948 subjects, 480 girls and 468 boys, between 1 and 11 years of age,
      were included in this study. All assays were performed on a Roche cobas e 411
      immunoassay analyzer. Reference intervals have been evaluated according to the
      most recent CLSI guidelines. RESULTS: Median values of LH, FSH and T were
      significantly higher in subgroups ranging from >= 8 to < 11 years, for both
      genders. In girls of that age, reference values of E2 were significantly higher
      than in younger ones, and in boys of the corresponding age. CONCLUSION:
      Established reference intervals are applicable to other laboratories that use the
      same instrumentation.

PMID- 22634600
TI  - First report of endocarditis by Gluconobacter spp. in a patient with a history of
      intravenous-drug abuse.
AB  - Gluconobacter belongs to the acetic acid bacteria (AAB), which are microorganisms
      commonly found in the environment and used in the food industry. These bacteria
      have increasingly been reported as organisms that can potentially infect humans.
      We report a case of Gluconobacter spp. bloodstream infection associated with
      endocardial lesions in a 25 year-old female intravenous drug abuser. To the best
      of our knowledge, this is the first case of Gluconobacter spp. endocarditis
      reported in the literature. For the first time we report that a multiresistant
      strain belonging to the genus Gluconobacter can cause endocarditis, giving
      evidence to the fact that this microorganism should be considered a new
      opportunistic human pathogen.

PMID- 22634602
TI  - A systematized interdisciplinary nutritional care plan results in improved
      clinical outcomes.
AB  - OBJECTIVE: This study investigated identification and treatment of patients at
      risk for malnutrition and extended inpatient length of stay. DESIGN: Data were
      collected retrospectively from the medical records for a period of 6 months. The
      records were reviewed for (1) adherence to RD recommendation, (2) decreasing
      serum albumin during hospital stay, (3) length of hospital stay, (4) readmission
      within 30 days, (5) age, (6) gender, (7) past medical history, (8) primary and
      secondary diagnoses, (9) the presence or absence of a diet order and (10)
      medications. SUBJECTS AND PARTICIPANTS: Medical records were reviewed for
      diagnoses associated with nutrition-related complications. Patient's records were
      excluded for length of stay less than 4 days, or in-hospital death. RESULTS: The
      mean LOS was 10 days shorter when the advice was followed (p=0.0074).
      CONCLUSIONS: Patients at high nutritional risk have a shorter LOS and have fewer
      complications when the RD advice is followed.

PMID- 22634603
TI  - Changes of blood platelet adhesion to collagen and fibrinogen induced by
      homocysteine and its thiolactone.
AB  - BACKGROUND: Mechanisms of homocysteine (Hcy) and its derivatives contribution to
      thrombosis are complex and are only partly recognized. The available data suggest
      that the prothrombic properties of homocysteine and its thiolactone (HTL) are not
      only a result of the changes in coagulation process, fibrinolysis, or endothelial
      dysfunction, but also the dysfunction of blood platelets. OBJECTIVE AND METHODS:
      The present work was designed to study the effects of Hcy and HTL on one of the
      step of platelet activation - the platelet adhesion to collagen and fibrinogen in
      vitro. Platelet suspensions were preincubated with Hcy and HTL, at the final
      concentrations of 10, 25, 50 and 100 MUM, and 0.1, 0.2 and 1 MUM, respectively.
      Then, for platelet activation thrombin (0.1 U/mL) or TRAP (20 MUM), were used.
      RESULTS: The performed assays demonstrated that Hcy (at high tested
      concentrations: 50 and 100 MUM) and its thiolactone (at all used concentrations:
      0.1, 0.2 and 1 MUM) stimulated the adhesion of thrombin- or TRAP- activated
      platelets to collagen and fibrinogen. Moreover, the exposure of blood platelets
      to HTL (even at lower concentrations than Hcy) resulted to a stronger modulatory
      effect on the platelet adhesion than when blood platelets were treated with Hcy.
      CONCLUSION: In conclusion, the results obtained in this study demonstrate that
      Hcy and its thiolactone may affect adhesive properties of blood platelets.

PMID- 22634604
TI  - Inhibition kinetics and regulation of sphingosine kinase 1 expression in prostate
      cancer cells: functional differences between sphingosine kinase 1a and 1b.
AB  - Sphingosine kinase 1 catalyses the formation of the bioactive lipid, sphingosine
      1-phosphate and is a target for anti-cancer agents. We demonstrate here that 2-(p
      hydroxyanilino)-4-(p-chlorophenyl)thiazole (SKi, also referred to as SKI-II),
      FTY720 (Fingolimod), and (S)-FTY720 vinylphosphonate inhibit sphingosine kinase 1
      activity with distinct kinetics, indicating that these compounds exhibit
      different binding modalities with sphingosine kinase 1. Thus, SKi is a mixed
      inhibitor of sphingosine and ATP binding, whereas FTY720 is competitive with
      sphingosine and uncompetitive with ATP, and (S)-FTY720 vinylphosphonate is
      uncompetitive with sphingosine and is a mixed inhibitor with respect to ATP. A
      novel 'see-saw' model is proposed for the binding of inhibitor to catalytic and
      allosteric sites, the latter dependent on substrate binding, that provides an
      explanation for the different inhibitor kinetics. In addition, we demonstrate
      that the expression level and properties unique to an N-terminal 86 amino-acid
      isoform variant of sphingosine kinase 1 (SK1b) in prostate cancer cells reduce
      its sensitivity to SKi-induced proteasomal degradation in comparison to SK1a,
      i.e. these two N-terminal variants of sphingosine kinase 1 (SK1a and SK1b) have
      different properties. The reduced sensitivity of SK1b to proteasomal degradation
      in response to SKi is translated into specific changes in ceramide and S1P levels
      that leads to apoptosis of androgen-sensitive but not androgen-independent LNCaP
      prostate cancer cells. Therefore, our proposed 'see-saw' model might be usefully
      employed in the design of sphingosine kinase inhibitors to promote apoptosis of
      chemotherapeutic resistant cancer cells.

PMID- 22634605
TI  - Tenascin-R: role in the central nervous system.
AB  - Tenascin-R (TN-R), a member of the tenascin family of extracellular matrix
      glycoproteins, is exclusive to the nervous system. It affects cell migration,
      adhesion and differentiation, although no remarkable clinical consequences have
      been shown in knock-out animal models. TN-R's expression pattern suggests a
      possible primary or secondary role in certain neurological problems including
      malformations, tumors and neurodegenerative disorders. This review summarizes the
      structure and molecular interactions of this molecule and discusses its function
      and possible roles in the central nervous system.

PMID- 22634606
TI  - The WAP protein Trappin-2/Elafin: a handyman in the regulation of inflammatory
      and immune responses.
AB  - Trappin-2/Elafin is a potent serine protease inhibitor which prevents excessive
      damage under inflammatory status. This "alarm-antiprotease" is locally expressed
      by epithelial cells and immune cells such as macrophages and gammadelta T cells.
      It has also been proven to modulate a wide range of parameters that are critical
      for the inflammation process like modulating the NFkappaB pathway, cytokine
      secretion and cell recruitment. In addition, Trappin-2/Elafin was shown to
      possess anti-microbial properties against different classes of pathogens
      including viruses, fungi and bacteria. Studies also linked Trappin-2/Elafin to
      either susceptibility or protection against inflammatory disease and infections,
      even though the mechanisms remains poorly understood. This review will discuss
      some of the pleiotropic effects displayed by Trappin-2/Elafin, and the properties
      that could be used to prevent infection or to protect against inflammation.

PMID- 22634607
TI  - Palvanil, a non-pungent capsaicin analogue, inhibits inflammatory and neuropathic
      pain with little effects on bronchopulmonary function and body temperature.
AB  - N-Palmitoyl-vanillamide (palvanil) is a non-pungent capsaicinoid, found in low
      amounts in Capsicum and shown to rapidly desensitize transient receptor potential
      vanilloid type-1 (TRPV1) channels to the action of capsaicin and to exert
      analgesic effects after local administration. We have investigated here if
      systemic administration of palvanil to mice causes two typical adverse events of
      TRPV1 agonists, i.e. profound changes in body temperature and
      bronchoconstriction, and if it can still produce effective inhibition of
      inflammatory and chronic pain in different experimental models. Varying doses of
      palvanil were tested subcutaneously and acutely on body temperature in vivo or,
      or as a bolus, on bronchopulmunary function ex vivo, in comparison with
      capsaicin. Intraperitoneal palvanil was also tested against formalin-induced
      nocifensive behavior and carrageenan-induced oedema and thermal hyperalgesia,
      acutely, and against mechanical allodynia and thermal hyperalgesia in mice with
      spared nerve injury (SNI) of the sciatic nerve, after repeated administration
      over 7 days from SNI. Palvanil, at therapeutically relevant doses, produced
      significantly less hypothermia and bronchoconstriction than capsaicin. Palvanil
      (0.5-2.5 mg/kg) abolished formalin-induced nocifensive behavior and strongly
      attenuated SNI-induced mechanical allodynia and thermal hyperalgesia and
      carrageenan-induced oedema and thermal hyperalgesia. Systemic administration of
      the non-pungent capsaicinoid, palvanil, produces, at least in mice, much less of
      those side effects typical of TRPV1 agonists (hypothermia and
      bronchoconstriction), whilst being very effective at reducing pain and oedema.
      Thus, palvanil might be developed further as a novel pharmacological treatment
      for chronic abnormal pain.

PMID- 22634608
TI  - The role of 3d electrons in the appearance of ferromagnetism in the
      antiferromagnetic Ru2MnGe Heusler compound: a magnetic Compton scattering study.
AB  - The antiferromagnetism in Ru(2)MnGe can be suppressed by the substitution of V by
      Mn and ferromagnetism appears. Synchrotron-based magnetic Compton scattering
      experiments are used in order to investigates the role of 3d electrons in the
      indirect/direct exchange interactions for the appearance of ferromagnetism. A
      small spin moment for the itinerant electron part on the magnetic Compton profile
      indicates that the metallic ferromagnet Ru(2)Mn(0.5)V(0.5)Ge has a weak indirect
      exchange interaction between the d-like and sp-like (itinerant) electrons. This
      suggests that the appearance of ferromagnetism is caused by the enhancement of
      the direct exchange interactions between d-d electrons in the Ru(2)MnGe Heusler
      compound. These findings indicate that the indirect exchange interaction between
      itinerant electrons and localized electrons is a significant key point for the
      appearance of ferromagnetism in this system.

PMID- 22634609
TI  - Interaction between GUVs and catanionic nanocontainers: new insight into
      spontaneous membrane fusion.
AB  - Spontaneous receptor-free membrane fusion with pure lipid systems, used as a cell
      membrane model, is demonstrated with easy-to-handle lactose-derived catanionic
      vesicles. This fusion, mediated and controlled by phospholipids, emphasizes the
      great value of these nanovesicles for enhanced direct cytosolic drug delivery
      without the shortcomings linked with endocytic pathways.

PMID- 22634610
TI  - Involvement of insulin-induced reversible chromatin remodeling in altering the
      expression of oxidative stress-responsive genes under hyperglycemia in 3T3-L1
      preadipocytes.
AB  - The epigenetic control mechanisms, regulating insulin-induced oxidative stress
      generation, under hyperglycemic condition are yet to be elucidated. We set out to
      assess the role of chromatin regulatory factors in regulating the transcription
      of genes that are critical for mediating oxidative stress response under
      hyperglycemic/hyperinsulinemic condition. Our results outline a significant
      increase in the ROS generation accompanied by a decrease in the histone H3
      acetylation, H3 Ser-10 phosphorylation, H3K4 methylation and an increase in the
      H3K9 methylation, after 30 min of insulin treatment under hyperglycemic
      condition. However, after 12h of insulin treatment a reversal of these histone H3
      modifications was observed which commensurate with the reduced ROS generation.
      Microarray data revealed that the expression of stress responsive genes (Hsp90,
      Hspd1, DnajC15, Hsf5 and Mapk3) decreased after12h of insulin treatment, after an
      initial increase at 30 min. We observed the direct regulation of these stress
      responsive genes by reversible histone modifications under
      hyperglycemic/hyperinsulinemic condition at both time intervals. Further, pre
      incubation with catalase attenuates these changes. To the best of our knowledge
      this is the first report that shows the role of reversible histone modifications
      in regulating oxidative stress-responsive genes under hyperglycemic condition in
      3T3-L1 preadipocytes.

PMID- 22634611
TI  - The salt-responsive transcriptome of Populus simonii * Populus nigra via DGE.
AB  - In this study, the dynamic transcriptome of poplar (Populus simonii * Populus
      nigra) was investigated under salt stress using Solexa/illumine digital gene
      expression (DGE) technique. A total of 5453, 2372, and 1770 genes were shown to
      be differentially expressed after exposure to NaCl for 3 days, 6 days and 9 days,
      respectively. Differential expression patterns throughout salt stress were
      identified for 572 genes. Gene ontology classification analysis of these
      differentially expressed genes revealed that numerous genes mapped to
      "transporter activity" and "response to stress". The dynamic transcriptome
      expression profiles of poplar under salt stress obtained in this study may
      provide useful insights for further analysis of the mechanism of high salinity
      tolerance in plants. Furthermore, these differentially expressed genes under salt
      stress may allow identification of potential genes as suitable targets for
      biotechnological manipulation with the aim of improving poplar salt tolerance.

PMID- 22634612
TI  - One-step continuous synthesis of biocompatible gold nanorods for optical
      coherence tomography.
AB  - We present a novel one-step flow process to synthesize biocompatible gold
      nanorods with tunable absorption and biocompatible surface ligands. Photothermal
      optical coherence tomography (OCT) of human breast tissue is successfully
      demonstrated using tailored gold nanorods designed to have strong absorption in
      the near-infrared range.

PMID- 22634613
TI  - Cathelicidin-related antimicrobial peptide is required for effective lung mucosal
      immunity in Gram-negative bacterial pneumonia.
AB  - Cathelicidins are a family of endogenous antimicrobial peptides that exert
      diverse immune functions, including both direct bacterial killing and
      immunomodulatory effects. In this study, we examined the contribution of the
      murine cathelicidin, cathelicidin-related antimicrobial peptide (CRAMP), to
      innate mucosal immunity in a mouse model of Gram-negative pneumonia. CRAMP
      expression is induced in the lung in response to infection with Klebsiella
      pneumoniae. Mice deficient in the gene encoding CRAMP (Cnlp(-/-)) demonstrate
      impaired lung bacterial clearance, increased bacterial dissemination, and reduced
      survival in response to intratracheal K. pneumoniae administration. Neutrophil
      influx into the alveolar space during K. pneumoniae infection was delayed early
      but increased by 48 h in CRAMP-deficient mice, which was associated with enhanced
      expression of inflammatory cytokines and increased lung injury. Bone marrow
      chimera experiments indicated that CRAMP derived from bone marrow cells rather
      than structural cells was responsible for antimicrobial effects in the lung.
      Additionally, CRAMP exerted bactericidal activity against K. pneumoniae in vitro.
      Similar defects in lung bacterial clearance and delayed early neutrophil influx
      were observed in CRAMP-deficient mice infected with Pseudomonas aeruginosa,
      although this did not result in increased bacterial dissemination, increased lung
      injury, or changes in lethality. Taken together, our findings demonstrate that
      CRAMP is an important contributor to effective host mucosal immunity in the lung
      in response to Gram-negative bacterial pneumonia.

PMID- 22634614
TI  - Bacterial RNA mediates activation of caspase-1 and IL-1beta release independently
      of TLRs 3, 7, 9 and TRIF but is dependent on UNC93B.
AB  - Recognition of foreign nucleic acids is important for the induction of an innate
      immune response against invading pathogens. Although the pathways involved in
      sensing bacterial DNA and viral RNA are now well established, only limited
      knowledge is available on mechanisms underlying recognition of bacterial RNA. It
      has been reported that intracellular delivery of Escherichia coli RNA activates
      the Nlrp3 inflammasome, but whether this is a general property of bacterial RNA
      remains unclear as are the pathways involved in pro-IL-1beta induction and
      caspase-1 activation by bacterial RNA. In this study, we report that bacterial
      RNA from both Gram-positive and Gram-negative bacteria induces activation of
      caspase-1 and secretion of IL-1beta by murine dendritic cells and bone-marrow
      derived macrophages. Stimulation was independent of the presence of 5'
      triphosphate termini and occurred with whole RNA preparations from bacteria but
      not from eukaryotes. Induction of pro-IL-1beta as well as the priming for caspase
      1 activation by bacterial RNA was dependent on UNC93B, an endoplasmic reticulum
      protein essential for delivery of TLRs to the endosome, whereas the established
      nucleic acid sensing endosomal TLRs 3, 7, and 9 were dispensable. Additionally,
      caspase-1 activation and IL-1beta production by transfected bacterial RNA were
      absent in MyD88-deficient cells but independent of TRIF. Thus, our data indicate
      the presence of a yet unidentified intracellular nucleic acid receptor involved
      in bacterial RNA-induced inflammasome activation and release of IL-1beta.

PMID- 22634615
TI  - Milk fat globule-epidermal growth factor-factor 8 attenuates neutrophil
      infiltration in acute lung injury via modulation of CXCR2.
AB  - Excessive neutrophil infiltration to the lungs is a hallmark of acute lung injury
      (ALI). Milk fat globule epidermal growth factor-factor 8 (MFG-E8) was originally
      identified for phagocytosis of apoptotic cells. Subsequent studies revealed its
      diverse cellular functions. However, whether MFG-E8 can regulate neutrophil
      function to alleviate inflammation is unknown. We therefore aimed to reveal MFG
      E8 roles in regulating lung neutrophil infiltration during ALI. To induce ALI,
      C57BL/6J wild-type (WT) and Mfge8(-/-) mice were intratracheally injected with
      LPS (5 mg/kg). Lung tissue damage was assessed by histology, and the neutrophils
      were counted by a hemacytometer. Apoptotic cells in lungs were determined by
      TUNEL, whereas caspase-3 and myeloperoxidase activities were assessed
      spectrophotometrically. CXCR2 and G protein-coupled receptor kinase 2 expressions
      in neutrophils were measured by flow cytometry. Following LPS challenge, Mfge8(-/
      ) mice exhibited extensive lung damage due to exaggerated infiltration of
      neutrophils and production of TNF-alpha, MIP-2, and myeloperoxidase. An increased
      number of apoptotic cells was trapped into the lungs of Mfge8(-/-) mice compared
      with WT mice, which may be due to insufficient phagocytosis of apoptotic cells or
      increased occurrence of apoptosis through the activation of caspase-3. In vitro
      studies using MIP-2-mediated chemotaxis revealed higher migration of neutrophils
      of Mfge8(-/-) mice than those of WT mice via increased surface exposures to
      CXCR2. Administration of recombinant murine MFG-E8 reduces neutrophil migration
      through upregulation of GRK2 and downregulation of surface CXCR2 expression.
      Conversely, these effects could be blocked by anti-alpha(v) integrin Abs. These
      studies clearly indicate the importance of MFG-E8 in ameliorating neutrophil
      infiltration and suggest MFG-E8 as a novel therapeutic potential for ALI.

PMID- 22634616
TI  - BLIMP-1 and STAT3 counterregulate microRNA-21 during plasma cell differentiation.
AB  - During cellular differentiation, mRNA transcription and translation require
      precise coordination. The mechanisms controlling this are not well defined. IL-21
      is an important regulator of plasma cell differentiation, and it controls the
      master regulator of plasma cell differentiation, B lymphocyte-induced maturation
      protein-1 (BLIMP-1), via STAT3 and IRF4. Among the other targets of STAT3 is
      microRNA-21 (miR-21). miR-21 is the most frequently deregulated microRNA in
      malignancy, including B cell lymphomas, and it has oncogenic potential downstream
      of STAT3. However, the regulation and function of miR-21 during plasma cell
      differentiation are not characterized. In contrast to the induction of miR-21
      observed in response to STAT3 activation in other systems, we demonstrate that
      miR-21 is repressed during IL-21-driven plasma cell differentiation. We explored
      the molecular basis for this repression and identify primary miR-21 transcription
      as a direct target of BLIMP-1-dependent repression, despite continued STAT3
      activation and phospho-STAT3 binding to the primary miR-21 promoter. Thus, STAT3
      and BLIMP-1 constitute an incoherent feed-forward loop downstream of IL-21 that
      can coordinate microRNA with mRNA expression during plasma cell differentiation.

PMID- 22634617
TI  - IL-2 requirement for human plasma cell generation: coupling differentiation and
      proliferation by enhancing MAPK-ERK signaling.
AB  - Mature B cell differentiation involves a well-established transcription factor
      cascade. However, the temporal dynamics of cell signaling pathways regulating
      transcription factor network and coordinating cell proliferation and
      differentiation remain poorly defined. To gain insight into the molecular
      processes and extrinsic cues required for B cell differentiation, we set up a
      controlled primary culture system to differentiate human naive B cells into
      plasma cells (PCs). We identified T cell-produced IL-2 to be critically involved
      in ERK1/2-triggered PC differentiation. IL-2 drove activated B cell
      differentiation toward PC independently of its proliferation and survival
      functions. Indeed, IL-2 potentiated ERK activation and subsequent BACH2 and IRF8
      downregulation, sustaining BLIMP1 expression, the master regulator for PC
      differentiation. Inhibition of the MAPK-ERK pathway, unlike STAT5 signaling,
      impaired IL-2-induced PC differentiation and rescued the expression profile of
      BACH2 and IRF8. These results identify IL-2 as a crucial early input in mature B
      cell fate commitment.

PMID- 22634618
TI  - Transcriptional regulation of murine IL-33 by TLR and non-TLR agonists.
AB  - IL-33, a member of the IL-1 family of cytokines, is produced by many cell types,
      including macrophages, yet its regulation is largely unknown. Treatment of
      primary murine macrophages with a panel of TLR (e.g., TLR2, TLR3, TLR4, and TLR9)
      agonists and non-TLR (e.g., MDA5, RIG-I) agonists revealed a pattern of gene and
      protein expression consistent with a role for IFN regulatory factor-3 (IRF-3) in
      the expression of IL-33. Accordingly, induction of IL-33 mRNA was attenuated in
      IRF-3(-/-) macrophages and TBK-1(-/-) mouse embryonic fibroblasts. Despite the
      fact that all IL-33 agonists were IRF-3 dependent, LPS-induced IL-33 mRNA was
      fully inducible in IFN-beta(-/-) macrophages, indicating that IL-33 is not
      dependent on IFN-beta as an intermediate. Epinephrine and Bordetella pertussis
      adenylate cyclase toxin (ACT), cAMP-activating agents, activate CREB and greatly
      synergize with LPS to induce IL-33 mRNA in macrophages. Both LPS-induced and
      ACT/LPS-enhanced expression of IL-33 mRNA was partially, but significantly,
      inhibited by the protein kinase A inhibitor H-89 but not by tyrosine kinase or
      protein kinase C inhibitors. Two IL-33 mRNA species derived from two alternative
      promoters encode full-length IL-33; however, the shorter "A" species is
      preferentially induced by all IL-33-inducing agonists except Newcastle disease
      virus, a RIG-I agonist that induced expression of both "A" and "B" transcripts.
      Together, these studies greatly extend what is currently known about the
      regulation of IL-33 induction in macrophages stimulated by bacterial and viral
      agonists that engage distinct innate immune signaling pathways.

PMID- 22634619
TI  - Full-length IL-33 promotes inflammation but not Th2 response in vivo in an ST2
      independent fashion.
AB  - Expression of IL-33 is elevated in patients with pulmonary diseases, and full
      length (not proteolytically processed) IL-33 is the predominant form in the lungs
      in health and disease. To determine whether activation of IL-33 is needed for
      functional effects, activities of full-length mouse and mature mouse (mm) forms
      of IL-33 were compared in vivo. Replication-deficient adenoviral constructs were
      used for gene delivery. Both isoforms caused pulmonary infiltration of
      lymphocytes and neutrophils, whereas mm IL-33 also caused pulmonary eosinophilia
      and goblet cell hyperplasia and increased expression of IL-4, IL-5, IL-13, IL-17,
      MCP-1, and KC. The different effects were not associated with differential
      release from IL-33-producing cells or by differences in subcellular distributions
      of IL-33 isoforms. Germline deficiency of the cell surface receptor chain ST2
      abrogated the mm IL-33-induced Th2-associated effects (pulmonary eosinophilia,
      goblet cell hyperplasia, and increased IL-4 and IL-5), yet the lymphocytic
      infiltration induced by full-length mouse IL-33 or mm IL-33 was not fully
      abrogated by the absence of ST2. The similar effects of IL-33 isoforms were
      associated with comparable regulation of gene expression, notably matrix
      metalloproteinases 3, 10, and 13. Thus, full-length IL-33 is functionally active
      in vivo in an ST2-independent fashion, and its effects are partially different
      from those of mature IL-33. The different effects of these isoforms, particularly
      the pro-Th2 effects of mature IL-33, are due to differential utilization of the
      IL-33R chain ST2, whereas their similar effects result from regulation of gene
      expression.

PMID- 22634620
TI  - Induction of prolonged asthma tolerance by IL-10-differentiated dendritic cells:
      differential impact on airway hyperresponsiveness and the Th2 immunoinflammatory
      response.
AB  - IL-10-differentiated dendritic cells (DC10s) can prevent allergen sensitization
      and reverse the asthma phenotype in mice with established disease. However,
      little is known about the time-frames over which this tolerance is effective. We
      report that at 2 wk after i.p. or transtracheal delivery of 1 * 10(6) OVA-, but
      not house dust mite- presenting, DC10s to OVA-asthmatic mice, significant
      diminution of airway hyperresponsiveness (AHR) was first apparent, whereas AHR
      was abrogated between 3 and 10 wk posttreatment. At 13 wk, AHR returned to
      pretreatment levels but could again be reversed by DC10 retreatment. The impact
      of a single DC10 treatment on airway eosinophil and Th2 cytokine responses to
      recall OVA challenge, and on OVA-specific IgE/IgG1 responses, was substantial at
      3 wk posttreatment, but progressively increased thereafter, such that at 8 mo,
      airway eosinophil and Th2 responses to recall allergen challenge remained ~85-95%
      suppressed relative to saline-treated asthmatic mice. Four biweekly DC10
      treatments, whether transtracheal or i.p., reduced all asthma parameters to near
      background by 8 wk, whereas s.c. DC10 treatments did not affect AHR but did
      reduce the airway Th2 responses (i.v. DC10 had no discernible effects). Repeated
      challenge of the DC10-treated mice with aerosolized OVA (100 MUg/ml) did not
      reverse tolerance, but treatment with the indoleamine-2,3-dioxygenase antagonist
      1-methyltryptophan or neutralizing anti-IL-10R from days 12 to 21 after DC10
      therapy partially reversed tolerance (Th2 cytokine responses, but not AHR). These
      findings indicate that DC10-induced Th2 tolerance in asthmatic animals is long
      lived, but that DC10s employ distinct mechanisms to affect AHR versus Th2
      immunoinflammatory parameters.

PMID- 22634621
TI  - alpha-1 antitrypsin promotes semimature, IL-10-producing and readily migrating
      tolerogenic dendritic cells.
AB  - Tolerogenic IL-10-positive CCR7-positive dendritic cells (DC) promote T
      regulatory (Treg) cell differentiation upon CCR7-dependent migration to draining
      lymph nodes (DLN). Indeed, in human DC deficiencies, Treg levels are low. alpha-1
      antitrypsin (AAT) has been shown to reduce inflammatory markers, promote a
      semimature LPS-induced DC phenotype, facilitate Treg expansion, and protect
      pancreatic islets from alloimmune and autoimmune responses in mice. However, the
      mechanism behind these activities of AAT is poorly understood. In this study, we
      examine interactions among DC, CD4(+) T cells, and AAT in vitro and in vivo. IL
      1beta/IFN-gamma-mediated DC maturation and effect on Treg development were
      examined using OT-II cells and human AAT (0.5 mg/ml). CCL19/21-dependent
      migration of isolated DC and resident islet DC was assessed, and CCR7 surface
      levels were examined. Migration toward DLN was evaluated by FITC skin painting,
      transgenic GFP skin tissue grafting, and footpad DC injection. AAT-treated
      stimulated DC displayed reduced MHC class II, CD40, CD86, and IL-6, but produced
      more IL-10 and maintained inducible CCR7. Upon exposure of CD4(+) T cells to OVA
      loaded AAT-treated DC, 2.7-fold more Foxp3(+) Treg cells were obtained. AAT
      treated cells displayed enhanced chemokine-dependent migration and low surface
      CD40. Under AAT treatment (60 mg/kg), DLN contained twice more fluorescence after
      FITC skin painting and twice more donor DC after footpad injection, whereas
      migrating DC expressed less CD40, MHC class II, and CD86. Intracellular DC IL-10
      was 2-fold higher in the AAT group. Taken together, these results suggest that
      inducible functional CCR7 is maintained during AAT-mediated anti-inflammatory
      conditions. Further studies are required to elucidate the mechanism behind the
      favorable tolerogenic activities of AAT.

PMID- 22634622
TI  - Constitutive plasmacytoid dendritic cell migration to the splenic white pulp is
      cooperatively regulated by CCR7- and CXCR4-mediated signaling.
AB  - Although the spleen plays an important role in host defense against infection,
      the mechanism underlying the migration of the innate immune cells, plasmacytoid
      dendritic cells (pDCs), into the spleen remains ill defined. In this article, we
      report that pDCs constitutively migrate into the splenic white pulp (WP) in a
      manner dependent on the chemokine receptors CCR7 and CXCR4. In CCR7-deficient
      mice and CCR7 ligand-deficient mice, compared with wild-type (WT) mice,
      substantially fewer pDCs were found in the periarteriolar lymphoid sheath of the
      splenic WP under steady-state conditions. In addition, the migration of
      adoptively transferred CCR7-deficient pDCs into the WP was significantly worse
      than that of WT pDCs, supporting the idea that pDC trafficking to the splenic WP
      requires CCR7 signaling. WT pDCs responded to a CCR7 ligand with modest
      chemotaxis and ICAM-1 binding in vitro, and priming with the CCR7 ligand enabled
      the pDCs to migrate efficiently toward low concentrations of CXCL12 in a CXCR4
      dependent manner, raising the possibility that CCR7 signaling enhances CXCR4
      mediated pDC migration. In agreement with this hypothesis, CCL21 and CXCL12 were
      colocalized on fibroblastic reticular cells in the T cell zone and in the
      marginal zone bridging channels, through which pDCs appeared to enter the WP.
      Furthermore, functional blockage of CCR7 and CXCR4 abrogated pDC trafficking into
      the WP. Collectively, these results strongly suggest that pDCs employ both CCR7
      and CXCR4 as critical chemokine receptors to migrate into the WP under steady
      state conditions.

PMID- 22634623
TI  - B and T lymphocyte attenuator mediates inhibition of tumor-reactive CD8+ T cells
      in patients after allogeneic stem cell transplantation.
AB  - Allogeneic stem cell transplantation (allo-SCT) can cure hematological
      malignancies by inducing alloreactive T cell responses targeting minor
      histocompatibility antigens (MiHA) expressed on malignant cells. Despite
      induction of robust MiHA-specific T cell responses and long-term persistence of
      alloreactive memory T cells specific for the tumor, often these T cells fail to
      respond efficiently to tumor relapse. Previously, we demonstrated the involvement
      of the coinhibitory receptor programmed death-1 (PD-1) in suppressing MiHA
      specific CD8(+) T cell immunity. In this study, we investigated whether B and T
      lymphocyte attenuator (BTLA) plays a similar role in functional impairment of
      MiHA-specific T cells after allo-SCT. In addition to PD-1, we observed higher
      BTLA expression on MiHA-specific CD8(+) T cells compared with that of the total
      population of CD8(+) effector-memory T cells. In addition, BTLA's ligand, herpes
      virus entry mediator (HVEM), was found constitutively expressed by myeloid
      leukemia, B cell lymphoma, and multiple myeloma cells. Interference with the BTLA
      HVEM pathway, using a BTLA blocking Ab, augmented proliferation of BTLA(+)PD-1(+)
      MiHA-specific CD8(+) T cells by HVEM-expressing dendritic cells. Notably, we
      demonstrated that blocking of BTLA or PD-1 enhanced ex vivo proliferation of MiHA
      specific CD8(+) T cells in respectively 7 and 9 of 11 allo-SCT patients. Notably,
      in 3 of 11 patients, the effect of BTLA blockade was more prominent than that of
      PD-1 blockade. Furthermore, these expanded MiHA-specific CD8(+) T cells
      competently produced effector cytokines and degranulated upon Ag reencounter.
      Together, these results demonstrate that BTLA-HVEM interactions impair MiHA
      specific T cell functionality, providing a rationale for interfering with BTLA
      signaling in post-stem cell transplantation therapies.

PMID- 22634624
TI  - Characterizing gene movements between chromosomes in Drosophila.
AB  - Genes occasionally change their location in the genome through inter-chromosomal
      duplication and loss. These changes happen as mistakes during recombination or
      through retrotransposition. In Han and Hahn 2011,(1) we surveyed the genomes of
      ten Drosophila species, to identify and characterize the gene transposition
      events in the history of these species. In the paper, we showed that the rate of
      gene transposition in Drosophila is higher than previously appreciated. To
      understand the process of gene transposition, we examined the sequences,
      locations, and functions of the transposed genes. Based on the elevated rate of
      sequence evolution in transposed genes and the frequent movements near the
      centromeres and telomeres, we could not reject the hypothesis that these are
      mutations fixed through relaxed selection. But, by examining the functions of
      transposed genes more carefully, we found that genes with male-specific functions
      and genes with female-specific functions move in opposite directions involving
      the X chromosome. We also found an over-representation of chromosome related
      functions among the transposed genes. These observations suggest the possibility
      of particular selection pressures contributing to gene transpositions in
      Drosophila.

PMID- 22634625
TI  - Aggravated chronic brain injury after focal cerebral ischemia in aquaporin-4
      deficient mice.
AB  - The water channel aquaporin-4 (AQP4) is important in brain water homeostasis, and
      is also involved in astrocyte growth and glial scar formation. It has been
      reported that AQP4 deficiency attenuates acute ischemic brain injury as a result
      of reducing cytotoxic edema. Here, we determined whether AQP4 deficiency
      influences chronic brain injury after focal cerebral ischemia induced by 30 min
      of middle cerebral artery occlusion (MCAO). AQP4(-/-) mice exhibited a lower
      survival rate and less body weight gain than wild-type mice, but their
      neurological deficits were similar to wild-type mice during 35 days after MCAO.
      At 35 days after MCAO, AQP4(-/-) mice showed more severe brain atrophy and cavity
      formation in the ischemic hemisphere as well as more neuronal loss in the
      hippocampus. Furthermore, astrocyte proliferation and glial scar formation were
      impaired in AQP4(-/-) mice. Therefore, AQP4 deficiency complicated by astrocyte
      dysfunction aggravates chronic brain injury after focal cerebral ischemia,
      suggesting that AQP4 may be important in the chronic phase of the post-ischemic
      recovery process.

PMID- 22634626
TI  - Retinal horizontal cells reduced in a rat model of congenital stationary night
      blindness.
AB  - This work was conducted to determine whether congenital stationary night
      blindness (CSNB), which is caused by a Cacna1f mutation, could affect development
      of second-order neurons in the retina, such as horizontal cells (HCs). The CSNB
      rats and age-matched wild type rats were sacrificed at postnatal days (PND) 15,
      30 and 60. Morphometric analyses of HCs, which were labeled by a primary antibody
      to calbindin D-28K, were performed at the light microscopic level on retinal
      cross sections and whole mount retinas. Calbindin D-28K was measured by western
      blotting in retinal samples. We found that the average number and density of HCs,
      Calbindin level and thickness of OPL were all decreased significantly in CSNB
      group compared to control group. These results indicated that second-order
      retinal neurons, such as horizontal cells, are affected by retinal degeneration.
      The relationship between the absence of HCs and the gene defect of CSNB requires
      further research.

PMID- 22634627
TI  - The age-dependent change in olfactory periglomerular neuronal populations is not
      affected by interrupting subventricular neuroblast migration in adult rats.
AB  - The olfactory bulb (OB) is rich in the number and variety of neurotransmitter and
      neuropeptide containing cells, in particular in the glomerular layer. Several
      reports suggest that numbers of some periglomerular phenotypes could change
      depending on age. However, it is unclear whether the different classes of
      periglomerular interneurons are modified or are maintained stable throughout
      life. Thus, our first objective was to obtain the absolute number of cells
      belonging to the different periglomerular phenotypes at adulthood. On the other
      hand, the olfactory bulb is continously supplied with newly generated
      periglomerular neurons produced by stem cells located in the subventricular zone
      (SVZ) and rostral migratory stream. Previously, we demonstrated that the
      implantation of a physical barrier completely prevents SVZ neuroblast migration
      towards the OB. Then, another objective of this study was to evaluate whether
      stopping the continuous supply of SVZ neuroblasts modified the different
      periglomerular populations throughout time. In summary, we estimated the total
      number of TH-IR, CalB-IR, CalR-IR and GAD-IR cells in the OB glomerular layer at
      several time points in control and barrier implanted adult rats. In addition, we
      estimated the volume of glomerular, granular and complete OB. Our main finding
      was that the number of the four main periglomerular populations is age-dependent,
      even after impairment of subventricular neuroblast migration. Furthermore, we
      established that these changes do not correlate with changes in the volume of
      glomerular layer.

PMID- 22634628
TI  - Eye enucleation activates the transcription nuclear factor kappa-B in the rat
      superior colliculus.
AB  - Ocular enucleation produces significant morphological and physiological changes
      in central visual areas. However, our knowledge of the molecular events resulting
      from eye enucleation in visual brain areas remains elusive. We characterized here
      the transcription nuclear factor kappa-B (NF-kappaB) activation induced by ocular
      enucleation in the rat superior colliculus (SC). We also tested the effectiveness
      of the synthetic glucocorticoid dexamethasone in inhibiting its activation.
      Electrophoretic mobility shift assays to detect NF-kappaB indicated that this
      transcription factor is activated in the SC from 1h to day 15 postlesion. The
      expression of p65 and p50 proteins in the nuclear extracts was also increased.
      Dexamethasone treatment was able to significantly inhibit NF-kappaB activation.
      These findings suggest that this transcriptional factor is importantly involved
      in the visual system short-term processes that ensue after retinal lesions in the
      adult brain.

PMID- 22634629
TI  - Commissural NTS lesions enhance the pressor response to central cholinergic and
      adrenergic activation.
AB  - Electrolytic lesions of the commissural nucleus of the solitary tract (commNTS)
      in rats enhance the pressor response to bilateral carotid occlusion or to
      intravenous infusion of hypertonic NaCl without changing baroreflex responses. In
      an opposite direction, commNTS lesions abolish the pressor responses to
      peripheral chemoreflex activation. These opposite effects of commNTS lesions
      apparently result from an impairment of sympathetic activation in one case and in
      a facilitation of vasopressin secretion in the others. In the present study, we
      investigated the effects of the electrolytic lesions of the commNTS in the
      pressor responses that depend on sympathetic activation and vasopressin secretion
      produced by central cholinergic or adrenergic activation with
      intracerebroventricular (i.c.v.) injections of carbachol or noradrenaline,
      respectively, in unanesthetized rats. Male Holtzman rats (280-320 g, n=8
      15/group) with acute (1 day) or chronic (21 days) sham or commNTS lesions (1
      mA*10 s) and a stainless steel cannula implanted in the lateral ventricle were
      used. Acute commNTS lesions increased the pressor response to i.c.v. injection of
      carbachol (0.5 nmol/1MU1) (52 +/- 2, vs. sham: 37 +/- 2mm Hg) or noradrenaline
      (80 nmol/1MUl) (45 +/- 6, vs. sham: 30 +/- 3 mm Hg), whereas chronic commNTS
      lesions did not affect the pressor responses to the same treatments. Lesions of
      the commNTS impaired chemoreflex responses produced by intravenous KCN, without
      changing baroreflex responses. The results suggest that commNTS-dependent
      inhibitory signals are involved in the modulation of the pressor responses to
      central cholinergic and adrenergic activation, probably limiting vasopressin
      secretion.

PMID- 22634630
TI  - Six-year experience with a hybrid stent graft prosthesis for extensive thoracic
      aortic disease: an interim balance.
AB  - OBJECTIVES: To avoid a two-stage surgical approach for complex thoracic aortic
      disease with its additive mortality and morbidity, a hybrid stent graft
      prosthesis was introduced 6 years ago for simultaneous treatment of the
      ascending, arch and descending aortas, relying proximally on a surgical suture
      line with an integrated distal stent graft for downstream splinting. We report
      the mid-term single-centre experience. METHODS: Between January 2005 and March
      2011, 77 patients (mean age 59 years, male 75%) with acute (AAD, n = 39) or
      chronic aortic dissection (CAD, n = 23) DeBakey type I or an extensive thoracic
      aortic aneurysm (TAA, n = 15) underwent one-stage repair. Periodic follow-up
      studies (100%, mean 29 months) included repeat aortic computed tomography
      imaging. Major adverse events (MAEs) were defined as permanent stroke, spinal
      cord injury and dialysis. RESULTS: In-hospital mortality was 10% (8 of 77). The
      incidence of MAE in AAD, CAD and TAA was 5, 13 and 20%, respectively. At the last
      follow-up, the complete thrombosis of the thoracic false lumen was 92% for AAD,
      91% for CAD and the full exclusion of aneurysms 100% in TAA. Throughout the
      follow-up, freedom from aortic disease-related death was 93% and 5-year survival
      79%. Freedom from distal reoperation was 94% in AAD, 95% in CAD and 100% in TAA
      and the incidence of distal stent graft extension 10% (8 of 77). CONCLUSIONS: The
      durable hybrid one-stage repair of complex thoracic aortic disease is feasible
      with acceptable mortality. Distal reintervention is infrequent and associated
      with low risk; thus, the indication for the optimization of the peripheral flow
      using the endovascular aortic repair techniques is gradually widened.

PMID- 22634632
TI  - Isolation and characterization of a novel lectin with antifungal and
      antiproliferative activities from Sophora alopecuroides seeds.
AB  - Sophora alopecuroides lectin (SAL), a novel lectin from the seeds of Sophora
      alopecuroides, was purified by ion-exchange chromatography on diethylaminoethyl
      (DEAE)- and carboxymethyl (CM)-Sepharose columns, followed by gel filtration on a
      Sephadex 75 10/300 GL column. SAL was found to be a monomer of 39916.3 Da, as
      determined by tricine-sodium dodecyl sulphate-polyacrylamide gel electrophoresis
      and high-performance liquid chromatography (HPLC). The N-terminal 10-amino acid
      sequence of SAL, KPWALSFSFG, resembles those of other legume lectins. SAL
      exhibits hemagglutinating activity against rabbit erythrocytes at 11.9 MUg/ml.
      Its hemagglutinating activity is stable in the pH range 7-11 and in the
      temperature range 30-90 degrees C, and is stimulated by Mn(2+). The
      hemagglutinating activity of SAL is most potently inhibited by 50-mM d-galactose.
      SAL suppresses mycelial growth in Penicillium digitatum and Alternaria alternata;
      the IC(50) of the antifungal activity toward P. digitatum and A. alternata were
      found to be 3.125 and 3.338 MUM, respectively. SAL suppresses the proliferation
      of human cervical cancer cells (HeLa) at an IC(50) of 6.25 MUM (P< 0.05). But it
      has no inhibiting effect on bacteria. This is the first report of a lectin from
      seeds of S. alopecuroides.

PMID- 22634633
TI  - Glutaredoxin serves as a reductant for methionine sulfoxide reductases with or
      without resolving cysteine.
AB  - Methionine sulfoxide reductases A and B (MsrA and MsrB) have been known to be
      thioredoxin (Trx)-dependent enzymes that catalyze the reduction of methionine
      sulfoxide in a stereospecific manner. This work reports that glutaredoxin,
      another major thiol-disulfide oxidoreductase, can serve as a reductant for both
      MsrA and MsrB. Glutaredoxins efficiently reduced 1-Cys MsrA lacking a resolving
      Cys, which is not reducible by Trx. Glutaredoxins also reduced 3-Cys MsrA
      containing two resolving Cys. The glutaredoxin-dependent activity of the 3-Cys
      MsrA was comparable with the Trx-dependent activity. The kinetic data suggest
      that 1-Cys MsrA is more efficiently reduced by glutaredoxin than 3-Cys form.
      Also, glutaredoxins could function as a reductant for 1-Cys MsrB lacking a
      resolving Cys as previously reported. In contrast to the previous report, 2-Cys
      MsrB containing a resolving Cys was reducible by the glutaredoxins. Collectively,
      this study demonstrates that glutaredoxins reduce MsrAs and MsrBs with or without
      resolving Cys.

PMID- 22634634
TI  - A biased ligand for OXE-R uncouples Galpha and Gbetagamma signaling within a
      heterotrimer.
AB  - Differential targeting of heterotrimeric G protein versus beta-arrestin signaling
      are emerging concepts in G protein-coupled receptor (GPCR) research and drug
      discovery, and biased engagement by GPCR ligands of either beta-arrestin or G
      protein pathways has been disclosed. Herein we report on a new mechanism of
      ligand bias to titrate the signaling specificity of a cell-surface GPCR. Using a
      combination of biomolecular and virtual screening, we identified the small
      molecule modulator Gue1654, which inhibits Gbetagamma but not Galpha signaling
      triggered upon activation of Galpha(i)-betagamma by the chemoattractant receptor
      OXE-R in both recombinant and human primary cells. Gue1654 does not interfere
      nonspecifically with signaling directly at or downstream of Gbetagamma. This
      hitherto unappreciated mechanism of ligand bias at a GPCR highlights both a new
      paradigm for functional selectivity and a potentially new strategy to develop
      pathway-specific therapeutics.

PMID- 22634635
TI  - Deciphering biased-agonism complexity reveals a new active AT1 receptor entity.
AB  - Functional selectivity of G protein-coupled receptor (GPCR) ligands toward
      different downstream signals has recently emerged as a general hallmark of this
      receptor class. However, pleiotropic and crosstalk signaling of GPCRs makes
      functional selectivity difficult to decode. To look from the initial active
      receptor point of view, we developed new, highly sensitive and direct
      bioluminescence resonance energy transfer-based G protein activation probes
      specific for all G protein isoforms, and we used them to evaluate the G protein
      coupling activity of [(1)Sar(4)Ile(8)Ile]-angiotensin II (SII), previously
      described as an angiotensin II type 1 (AT(1)) receptor-biased agonist that is G
      protein independent but beta-arrestin selective. By multiplexing assays sensing
      sequential signaling events, from receptor conformations to downstream signaling,
      we decoded SII as an agonist stabilizing a G protein-dependent AT(1A) receptor
      signaling module different from that of the physiological agonist angiotensin II,
      both in recombinant and primary cells. Thus, a biased agonist does not
      necessarily select effects from the physiological agonist but may instead
      stabilize and create a new distinct active pharmacological receptor entity.

PMID- 22634636
TI  - Divergence of multimodular polyketide synthases revealed by a didomain structure.
AB  - The enoylreductase (ER) is the final common enzyme from modular polyketide
      synthases (PKSs) to be structurally characterized. The 3.0 A-resolution structure
      of the didomain comprising the ketoreductase (KR) and ER from the second module
      of the spinosyn PKS reveals that ER shares an ~600-A(2) interface with KR
      distinct from that of the related mammalian fatty acid synthase (FAS). In
      contrast to the ER domains of the mammalian FAS, the ER domains of the second
      module of the spinosyn PKS do not make contact across the two-fold axis of the
      synthase. This monomeric organization may have been necessary in the evolution of
      multimodular PKSs to enable acyl carrier proteins to access each of their cognate
      enzymes. The isolated ER domain showed activity toward a substrate analog,
      enabling us to determine the contributions of its active site residues.

PMID- 22634638
TI  - Effect of tissue-specific acetylcholinesterase inhibitor C-547 on alpha3beta4 and
      alphabetaepsilondelta acetylcholine receptors in COS cells.
AB  - The C-547 is the most effective muscle and tissue-specific anticholinesterase
      among alkylammonium derivatives of 6-methyluracil (ADEMS) acting in nanomolar
      concentrations on locomotor muscles but not on respiratory muscles, smooth
      muscles and heart and brain acetylcholine esterases (AChE). When applied
      systematically it could influence peripheral acetylcholine receptors. The aim of
      the present study was to investigate the effect of C-547 on rat alpha3beta4
      (ganglionic type) and alphabetaepsilondelta (muscle type) nicotinic receptors
      expressed in COS cells. Currents evoked by rapid application of acetylcholine or
      nicotine were recorded in whole-cell mode by electrophysiological patch-clamp
      technique 2-4 days after cell transfection by plasmids coding the alpha3beta4 or
      alphabetaepsilondelta combination of receptor subunits. In cells sensitive to
      acetylcholine, the application of C-547 evoked no responses. When acetylcholine
      was applied during an already running application of C-547, acetylcholine
      responses were only inhibited at concentrations higher than 10(-7)M. This
      inhibition is not voltage-dependent, but is accompanied by an increased rate of
      desensitization. Thus in both types of receptors, effective doses are
      approximately 100 times higher than those inhibiting AChE in leg muscles and
      similar to those inhibiting respiratory diaphragm muscles and external
      intercostal muscles. These observations show that C-547 can be considered for
      symptomatic treatment of myasthenia gravis and other congenital myasthenic
      syndromes as an inhibitor of AChE in leg muscles at concentrations much lower
      than those inhibiting muscle and ganglion types of acetylcholine receptors.

PMID- 22634637
TI  - Direct and selective small-molecule activation of proapoptotic BAX.
AB  - BCL-2 family proteins are key regulators of the apoptotic pathway. Antiapoptotic
      members sequester the BCL-2 homology 3 (BH3) death domains of proapoptotic
      members such as BAX to maintain cell survival. The antiapoptotic BH3-binding
      groove has been successfully targeted to reactivate apoptosis in cancer. We
      recently identified a geographically distinct BH3-binding groove that mediates
      direct BAX activation, suggesting a new strategy for inducing apoptosis by
      flipping BAX's 'on switch'. Here we applied computational screening to identify a
      BAX activator molecule that directly and selectively activates BAX. We
      demonstrate by NMR and biochemical analyses that the molecule engages the BAX
      trigger site and promotes the functional oligomerization of BAX. The molecule
      does not interact with the BH3-binding pocket of antiapoptotic proteins or
      proapoptotic BAK and induces cell death in a BAX-dependent fashion. To our
      knowledge, we report the first gain-of-function molecular modulator of a BCL-2
      family protein and demonstrate a new paradigm for pharmacologic induction of
      apoptosis.

PMID- 22634639
TI  - Cornea fellowship training and refractive surgery:  standard requirements.
AB  - PURPOSE OF REVIEW: The Association of University Professors of Ophthalmology
      Fellowship Compliance Committee (AUPO FCC) provides standardized guidelines for
      seven ophthalmology subspecialties. Participation in this process is on a
      voluntary basis. The subspecialty of Cornea, External Disease and Refractive
      Surgery (CEDRS) was one of the first to join the AUPO FCC compliance process.
      This article reviews the development of subspecialty guidelines, the
      establishment of the AUPO FCC, and the impact of fellowship training on the
      ophthalmology community. Particular attention is given to the effect of this
      process on CEDRS fellowship requirements. RECENT FINDINGS: There have been few
      studies evaluating the surgical outcomes of cornea fellows during training.
      Overall, these studies concluded that cornea/refractive surgery fellows achieve
      similar postoperative results when compared with more experienced senior faculty.
      Extensive preoperative training and guided supervision were the main factors that
      contributed to successful surgical outcomes. SUMMARY: The establishment of
      guidelines in various ophthalmology fellowships has been generally accepted as a
      method to ensure a more uniform and comprehensive training experience.
      Additionally, the presence of fellows at an academic institution often enhances
      the education of residents. Fellows also contribute to the field with their
      participation in basic science and clinical research. Under proper guidance and
      supervision, cornea fellows can achieve surgical outcomes that are comparable to
      experienced surgeons. The additional training offered in fellowship helps develop
      a subset of physicians with advanced clinical and surgical skills.

PMID- 22634640
TI  - Anterior segment uses of bevacizumab.
AB  - PURPOSE OF REVIEW: A significant recent advancement in the treatment of
      neovascularization of the anterior segment of the eye is the development of
      antivascular endothelial growth factor (anti-VEGF) therapeutic agents.We present
      a review of the current knowledge on anti-VEGF therapy with bevacizumab for
      anterior segment neovascularization. RECENT FINDINGS: A review of the recent peer
      reviewed literature reveals an increasing number of experimental and clinical
      studies on the use of Avastin in both human and animal eye models. Although the
      numbers are still relatively small, the evidence suggests that bevacizumab may be
      effective in the treatment of corneal and iris neovascularization. Its effect on
      primary and recurrent pterygium is more controversial. In general, achievement of
      vessels regression is usually partial, and recurrence may occur after cessation
      of treatment. Response to treatment is affected by the chronicity of vessels,
      their extent, the cause for blood vessels formation, and the route of
      administration. SUMMARY: Effective short-term response together with high patient
      tolerance to local bevacizumab therapy offer encouraging results for the
      management of anterior segment neovascular disorders. Although statistically
      significant regression of vessels has been documented in many studies, the
      clinical significance of this finding is still a subject of debate.

PMID- 22634641
TI  - Discussion: AlloDerm and Strattice in breast reconstruction: a comparison and
      techniques for optimizing outcomes.

PMID- 22634642
TI  - Safety, efficacy, and modifications of the dermal bra technique for reduction
      mammaplasty and ptosis correction:  a 10-year retrospective study.
AB  - BACKGROUND: The dermal bra technique was reported by the authors in 2003 for
      reduction mammaplasty and ptosis correction. The authors have summarized and
      modified continuously and here share their experience and analyze the long-term
      safety and efficacy of this technique. METHODS: Three hundred forty-seven
      patients underwent the dermal bra technique in the authors' department from
      October of 2003 to October of 2011, and 213 of them were followed successfully
      for 3 months to 2 years. Patients before and after October of 2006 were divided
      into early and late groups. The incidence of complications, the long-term
      satisfaction rate, and modifications that have been developed were noted and
      analyzed. RESULTS: Short-term complications occurred in 55 breasts (7.9 percent),
      including hematoma (seroma), delayed wound healing, fat necrosis, deep folds,
      necrosis, and numbness of the nipple-areola complex. Long-term complications were
      found in 28 breasts (6.6 percent), including widened scar and enlarged areola,
      irregular areola, secondary ptosis, sunken nipple-areola complex, numbness of the
      nipple-areola complex, cyst, and chronic infection. Except for one case of nipple
      areola complex numbness, all complications were corrected successfully. The long
      term satisfaction rate was 95.7 percent. With three major modifications (W- or V
      shaped gland resection, medial rotation of gland flap, and modified purse-string
      suture), the short-term and long-term complication rates (p < 0.01) and
      satisfaction rate (p < 0.05) of the late group were improved significantly
      compared with the early group. CONCLUSION: Effective modifications have
      significantly improved the safety and efficacy of the dermal bra technique and
      have made it a mature approach for reduction mammaplasty and ptosis correction.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22634643
TI  - Deep and superficial keloid fibroblasts contribute differentially to tissue
      phenotype in a novel in vivo model of keloid scar.
AB  - BACKGROUND: Keloids are thick fibrous scars that are refractory to treatment and
      unique to humans. The lack of keloid animal models has hampered development of
      effective therapies. The authors' goal was to develop an animal model of keloids
      using grafted engineered skin substitutes composed of keloid-derived cells. To
      demonstrate the model's utility, differences between deep and superficial keloid
      fibroblasts were investigated. METHODS: Engineered skin substitutes were prepared
      using six combinations of cells: 1, normal keratinocytes and normal fibroblasts;
      2, normal keratinocytes and deep keloid fibroblasts; 3, normal keratinocytes and
      superficial keloid fibroblasts; 4, keloid keratinocytes and normal fibroblasts;
      5, keloid keratinocytes and deep keloid fibroblasts; and 6, keloid keratinocytes
      and superficial keloid fibroblasts. Engineered skin substitutes stably grafted to
      athymic mice were evaluated for wound area, thickness, and gene expression.
      RESULTS: Deep keloid fibroblasts displayed elevated expression of type 1 collagen
      alpha 1 (COL1A1), transforming growth factor beta-1, periostin, plasminogen
      activator inhibitor 2, and inhibin beta A compared with superficial keloid
      fibroblasts and normal fibroblasts. After grafting, engineered skin substitutes
      in group 5 were significantly thicker than controls and had increased COL1A1
      expression. Engineered skin substitutes in group 6 showed significantly increased
      area. Histologic analysis revealed abnormal collagen organization in engineered
      skin substitutes containing deep keloid fibroblasts or superficial keloid
      fibroblasts. CONCLUSIONS: Aspects of the phenotypes of engineered skin
      substitutes prepared with keloid cells are analogous to thickening and spreading
      of human keloid scars. Therefore, use of keloid engineered skin substitutes is a
      valuable new tool for the study of keloid scarring.

PMID- 22634644
TI  - Scar zones:  region-specific differences in skin tension may determine incisional
      scar formation.

PMID- 22634645
TI  - Human adipose stem cells:  current clinical applications.
AB  - Adipose-derived stem cells are multipotent cells that can easily be extracted
      from adipose tissue, are capable of expansion in vitro, and have the capacity to
      differentiate into multiple cell lineages, which have the potential for use in
      regenerative medicine. However, several issues need to be studied to determine
      safe human use. For example, there are questions related to isolation and
      purification of adipose-derived stem cells, their effect on tumor growth, and the
      enforcement of U.S. Food and Drug Administration regulations. Numerous studies
      have been published, with the interest in the potential for regenerative medicine
      continually growing. Several clinical trials using human adipose stem cell
      therapy are currently being performed around the world, and there has been a
      rapid evolution and expansion of their number. The purpose of this article was to
      review the current published basic science evidence and ongoing clinical trials
      involving the use of adipose-derived stem cells in plastic surgery and in
      regenerative medicine in general. The results of the studies and clinical trials
      using adipose-derived stem cells reported in this review seem to be promising not
      only in plastic surgery but also in a wide variety of other specialties.
      Nevertheless, those reported showed disparity in the way adipose-derived stem
      cells were used. Further basic science experimental studies with standardized
      protocols and larger randomized trials need to be performed to ensure safety and
      efficacy of adipose-derived stem cells use in accordance with U.S. Food and Drug
      Administration guidelines.

PMID- 22634646
TI  - Discussion: Simplifying cheek reconstruction: a review of over 400 cases.

PMID- 22634648
TI  - Bone biology and physiology: Part I. The fundamentals.
AB  - The principles of bone biology and physiology permeate all subspecialty practices
      in plastic and reconstructive surgery from hand surgery to aesthetic surgery.
      Despite its importance in our practices, the biology of bone healing and bone
      physiology rarely surfaces within textbooks, literature reviews, or residency
      curricula. In this article, the authors present the first of a two-part series
      reviewing the important concepts of bone biology and bone physiology relevant to
      plastic surgery in an effort to ameliorate this educational gap.

PMID- 22634647
TI  - Robotic latissimus dorsi muscle harvest:  a case series.
AB  - BACKGROUND: The latissimus dorsi muscle is a workhorse of reconstructive surgery.
      Traditional harvest technique requires a long, posterior donor-site incision.
      Endoscopic harvest is limited by technical challenges. Robotic technology permits
      a simpler, minimally invasive harvest technique. METHODS: Seven consecutive
      robotic latissimus dorsi muscle harvests were performed by a single surgeon. Two
      were used as free flaps for scalp reconstruction and the remaining five as
      pedicled flaps for breast reconstruction; three were for immediate, implant-based
      reconstruction with nipple-areola complex-sparing mastectomies, and two were for
      radiated breasts when the expander was exchanged for an implant. Harvest
      technique employed a short, axillary incision for pedicle dissection and two to
      three additional ports for robotic instrumentation. RESULTS: All seven muscle
      flaps were harvested without converting to an open technique. Both free flaps
      were successfully transferred. All pedicled flaps resulted in successful breast
      reconstructions. Flap harvest complications included a single, temporary radial
      nerve palsy in the contralateral extremity, likely from positioning. There were
      no donor-site hematomas, seromas, or cutaneous thermal injuries. Robotic harvest
      time decreased from over 2 hours to about an hour over the study period.
      CONCLUSIONS: Robotic harvest of the latissimus dorsi is a novel and effective
      method of muscle harvest. It offers technical advantages over endoscopic harvest
      and aesthetic advantages over the open technique. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 22634649
TI  - Discussion: Repair of Tessier no. 3 and no. 4 craniofacial clefts with facial
      unit and muscle repositioning by midface rotation advancement without Z-plasties.

PMID- 22634650
TI  - Current surgical management of bilateral cleft lip in North America.
AB  - BACKGROUND: This study was undertaken to determine contemporary surgical
      management of bilateral cleft lip. METHODS: A survey was sent to North American
      cleft surgeons. Variables included number of bilateral cleft lip repairs per
      year, surgical specialty, and methods of nasolabial correction. The authors
      analyzed possible relationships between surgical specialty/volume and operative
      techniques. RESULTS: The response rate was 40 percent (241 of 600). Annual
      bilateral nasolabial repairs per surgeon were as follows: zero to two, 30
      percent; three to five, 46 percent; and six or more, 25 percent. For bilateral
      complete cleft lip, dentofacial orthopedics was used by 71 percent of
      respondents; synchronous closure was most commonly performed (88 percent);
      infrequent techniques were preliminary labial adhesions (11 percent) and staged
      labial closure (1 percent); and 50 percent undertook primary nasal repair. One
      half of respondents used nostril splinting following primary or secondary nasal
      correction. For bilateral incomplete cleft lip, 90 percent of surgeons performed
      synchronous labial repair and 36 percent did primary nasal correction. For both
      complete and incomplete bilateral cleft lips, high-volume surgeons were more
      likely to excise prolabial vermilion and use lateral vermilion-mucosal flaps to
      form the median tubercle. For bilateral asymmetrical cleft lip, 85 percent of
      surgeons practiced synchronous labial repair and 54 percent used dentofacial
      orthopedics on the complete side. CONCLUSIONS: Synchronous repair was the most
      frequent method for bilateral cleft lip; one-half of surgeons practiced primary
      nasal correction. There were no associations between surgical specialty/volume
      and operative principles or techniques for bilateral nasolabial repair, except
      for construction of the median tubercle.

PMID- 22634651
TI  - Discussion: Current surgical management of bilateral cleft lip in North America.

PMID- 22634652
TI  - An analysis of the experiences of 62 patients with moderate complications after
      full-face fat injection for augmentation.
AB  - BACKGROUND: Recently, fat injection has been performed across the globe and has
      several advantages. However, there have not been many studies regarding the
      relationship between complications and contributing factors. The authors analyzed
      factors present when complications occurred during fat injections into the face.
      METHODS: A retrospective chart review was performed for 62 patients who had
      moderate complications among the 1261 persons who had received full-face fat
      injection between April of 2004 and July of 2008. Complications included chronic
      edema, calcification, fibrosis, acne, headache, dysesthesia, drooping, and
      irregularity. RESULTS: There were no differences among the first, second, and
      third injection groups regarding age, body weight, height, or body mass index.
      However, there were statistically significant differences in injection amount and
      complication occurrence time (p < 0.0001). There were statistically significant
      differences in injection amount and complication occurrence time between the
      fresh and frozen fat (p < 0.0001). There were statistically significant
      differences regarding age, injection amount, and complication occurrence time
      according to the complication groups (p < 0.0001). There was also a difference
      between timing of the injection and the complication frequency (Fisher's exact
      test, p < 0.0001) and between fat status and the complication frequency (Fisher's
      exact test, p = 0.005). CONCLUSIONS: Chronic edema, calcification, fibrosis,
      acne, headache, dysesthesia, drooping, and irregularity after full-face fat
      injection were observed as moderate complications. Although further study will be
      needed for the effective analysis of complications according to the number of
      injection or fat status, the authors found significant differences in age,
      complication occurrence time, and injection amount between some complication
      groups. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

PMID- 22634653
TI  - Discussion: An analysis of the experiences of 62 patients with moderate
      complications after full-face fat injection for augmentation.

PMID- 22634654
TI  - Prevalence of rupture in poly implant Prothese silicone breast implants, recalled
      from the European market in 2010.
AB  - BACKGROUND: Known complications of silicone breast implants are rupture and
      silicone leakage, complications that are related not only to generation and
      implant age but also to the manufacturer. Implants from the French manufacturer
      Poly Implant Prothese showed more rupture than expected and were banned from the
      European market in 2010. Clinics in Europe recalled their patients, but
      prevalence of rupture in these implants has not been previously reported.
      METHODS: All women who underwent breast augmentation in 2000 and 2001 in the Jan
      van Goyen Clinic, Amsterdam, The Netherlands, were informed about concerns
      regarding the quality of their implants. Medical records were used to trace
      manufacturer and implantation specifics. One hundred twelve women with proven
      Poly Implant Prothese implants were enrolled in this study. All women underwent
      physical examination and magnetic resonance imaging and were interviewed for
      complaints to determine the prevalence of symptomatic and asymptomatic rupture.
      RESULTS: Two hundred twenty-four Poly Implant Prothese implants were evaluated
      with a mean implant age of 122 months. Of these 224 implants, 54 had ruptured.
      Magnetic resonance imaging showed that 33 percent of women had at least one
      ruptured implant. There was no significant difference in rupture rate of implants
      manufactured in 2000 and 2001. CONCLUSIONS: One third of the women who had
      undergone breast augmentation with Poly Implant Prothese implants were shown to
      have at least one ruptured implant after 10 years; 45.9 percent had bilateral
      rupture and 13.5 percent had extracapsular leakage. These were mostly
      asymptomatic ruptures. The rupture prevalence rate for Poly Implant Prothese
      implants after 10 years is 24 percent. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 22634655
TI  - Discussion: Prevalence of rupture in poly implant Prothese silicone breast
      implants, recalled from the European market in 2010.

PMID- 22634656
TI  - The tear trough ligament:  anatomical basis for the tear trough deformity.
AB  - BACKGROUND: The exact anatomical cause of the tear trough remains undefined. This
      study was performed to identify the anatomical basis for the tear trough
      deformity. METHODS: Forty-eight cadaveric hemifaces were dissected. With the skin
      over the midcheek intact, the tear trough area was approached through the
      preseptal space above and prezygomatic space below. The origins of the palpebral
      and orbital parts of the orbicularis oculi (which sandwich the ligament) were
      released meticulously from the maxilla, and the tear trough ligament was isolated
      intact and in continuity with the orbicularis retaining ligament. The ligaments
      were submitted for histologic analysis. RESULTS: A true osteocutaneous ligament
      called the tear trough ligament was consistently found on the maxilla, between
      the palpebral and orbital parts of the orbicularis oculi, cephalad and caudal to
      the ligament, respectively. It commences medially, at the level of the insertion
      of the medial canthal tendon, just inferior to the anterior lacrimal crest, to
      approximately the medial-pupil line, where it continues laterally as the
      bilayered orbicularis retaining ligament. Histologic evaluation confirmed the
      ligamentous nature of the tear trough ligament, with features identical to those
      of the zygomatic ligament. CONCLUSIONS: This study clearly demonstrated that the
      prominence of the tear trough has its anatomical origin in the tear trough
      ligament. This ligament has not been isolated previously using standard
      dissection, but using the approach described, the tear trough ligament is clearly
      seen. The description of this ligament sheds new light on considerations when
      designing procedures to address the tear trough and the midcheek.

PMID- 22634657
TI  - Discussion: The tear trough ligament: anatomical basis for the tear trough
      deformity.

PMID- 22634658
TI  - Benchmarking academic plastic surgery services in the United States.
AB  - Rising health care costs and increasingly demanding patients are only some of the
      challenges faced by academic plastic surgery services in their pursuit of
      excellence in education, research, and patient care. Benchmarking, when correctly
      applied, is a powerful tool that can help services learn from each other's
      experiences. This study aimed at creating the first benchmarking report
      summarizing performance indicators and management practices of some of the most
      complete academic plastic surgery units in the United States. Results provide an
      opportunity for plastic surgery leaders to benchmark against their own units,
      identify eventual gaps, and improve their performance as needed.

PMID- 22634659
TI  - Complications in surgery:  root cause analysis and preventive measures.
AB  - Patients expect to receive quality medical care by relying on the concepts of
      evidence-based medicine. This quality care is expected to be provided at
      decreased costs for payors, some of whom have stopped reimbursement for cases
      involving "reasonably preventable" surgical complications. The purpose of this
      article is to introduce root cause analysis as a tool for identifying the causes
      of surgical complications. The authors also discuss preventive measures, such as
      improved communication, checklists, reporting systems, and the use of evidence
      based medicine, that have been implemented to decrease surgical complications.
      These preventive measures can be used alone or together to decrease complications
      and improve overall patient care.

PMID- 22634660
TI  - Teaching plastic surgery from different perspectives.
AB  - Just as everyone has a different learning style, teachers too approach the task
      from different perspectives. There are five basic teaching perspectives or
      styles: transmission, apprenticeship, developmental, nurturing, and social
      justice. The acronym BIAS is useful to describe the beliefs, intentions,
      assessments, and strategies associated with each perspective. The authors present
      a hypothetical 1-week rotation in plastic and reconstructive surgery in which a
      student encounters instructors who embody the five basic teaching perspectives.
      By presenting these perspectives, the authors introduce valuable teaching
      techniques that can benefit all those charged with the education of learners
      along the spectrum from premedical to continuing education venues. Educational
      objectives include the following: (1) explain and illustrate different approaches
      to effective teaching in plastic surgery; (2) introduce readers to the Teaching
      Perspectives Inventory as a means of determining their primary teaching style;
      and (3) argue for a "plurality of the good" in teaching.

PMID- 22634661
TI  - So you want to be a change artist?

PMID- 22634662
TI  - Logging in to the PRS iPad app: access made easy.

PMID- 22634665
TI  - Retraction: Histologic results of neuronal anastomosis of the microvascular
      latissimus dorsi transplant.

PMID- 22634667
TI  - Is traditional lower blepharoplasty a superior technique?

PMID- 22634668
TI  - Outcome of different timings of radiotherapy in implant-based breast
      reconstructions.

PMID- 22634669
TI  - Secondary techniques in breast reconstruction refinement:  the periareolar
      advancement flap.

PMID- 22634671
TI  - V-Loc suture: a simple wound closure device for areola diameter and shape control
      in breast reduction and mastopexy.

PMID- 22634673
TI  - Postoperative stress-related stomach bleeding in a flap surgery patient.

PMID- 22634674
TI  - A prospective cohort study of fibula free flap donor-site morbidity in 157
      consecutive patients.

PMID- 22634675
TI  - Using statistical models to their full potential.

PMID- 22634677
TI  - Simulated frontoorbital advancement and intraoperative templates enhance
      reproducibility in craniosynostosis.

PMID- 22634678
TI  - Topical photodynamic therapy for idiopathic hirsutism and hypertrichosis.

PMID- 22634679
TI  - Ulthera for silicone lip correction.

PMID- 22634680
TI  - Current strategies in the treatment of gummy smile using botulinum toxin type A.

PMID- 22634681
TI  - Pharyngoplasty applied to velopharyngeal insufficiency: efficacy versus
      morbidity.

PMID- 22634682
TI  - Laser angiography as a predictor of mastectomy flap necrosis after breast
      reconstruction.

PMID- 22634683
TI  - The effects of antileukotriene agents on capsular contracture:  an evidence-based
      analysis.

PMID- 22634684
TI  - Measurement of breast volume after breast reconstruction using computed
      tomographic scanning.

PMID- 22634685
TI  - Microsurgical reconstruction of a huge mediastinal defect using thoracoacromial
      vessels as recipient pedicle.

PMID- 22634686
TI  - Fat harvesting:  spare your thumb, don't spoil the fat.

PMID- 22634687
TI  - Building bridges toward interdisciplinary surgical care.

PMID- 22634688
TI  - The effects of acellular dermal matrix in expander-implant breast reconstruction
      after total skin-sparing mastectomy:  results of a prospective practice
      improvement study.
AB  - BACKGROUND: Neither outcome after total skin-sparing mastectomy and expander
      implant reconstruction using acellular dermal matrix nor a strategy for optimal
      acellular dermal matrix selection criteria has been well described. METHODS:
      Prospective review of three patient cohorts undergoing total skin-sparing
      mastectomy with preservation of the nipple-areola complex and immediate expander
      implant reconstruction from 2006 to 2010 was performed. Cohort 1 (no acellular
      dermal matrix) comprised 90 cases in which acellular dermal matrix was not used.
      Cohort 2 (consecutive acellular dermal matrix) included the next 100 consecutive
      cases, which all received acellular dermal matrix. Cohort 3 (selective acellular
      dermal matrix) consisted of the next 260 cases, in which acellular dermal matrix
      was selectively used based on mastectomy skin flap thickness. Complication rates
      were compared using chi-square analysis. RESULTS: The study included 450 cases in
      288 patients. Mean follow-up was 25.5 months. Infection occurred in 27.8 percent
      of the no-acellular dermal matrix cases, 20 percent of the consecutive cases, and
      15.8 percent of the selective cases (p = 0.04). Unplanned return to the operating
      room was required in 23.3, 11, and 10 percent of cases, respectively (p = 0.004).
      Expander-implant loss occurred in 17.8, 7, and 5 percent of cases, respectively
      (p = 0.001). Additional analysis of the odds ratios of developing complications
      after postmastectomy radiation therapy demonstrated a specific protective benefit
      of acellular dermal matrix in irradiated patients. CONCLUSIONS: Acellular dermal
      matrix use in expander-implant reconstruction after total skin-sparing mastectomy
      reduced major postoperative complications in this study. Maximal benefit is
      achieved with selected use in patients with thin mastectomy skin flaps and those
      receiving radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      III.

PMID- 22634689
TI  - Comparison of immediate implant placement versus the staged tissue expander
      technique in breast reconstruction.
AB  - BACKGROUND: Tissue expansion is currently the most common method used in
      prosthetic breast reconstruction. Skin-sparing mastectomy techniques have
      facilitated immediate placement of a permanent implant. Proposed benefits to
      immediate implants include less time and fewer operations to complete
      reconstruction. Whether it leads to poorer outcomes remains unknown. The authors
      compared immediate implant-based and staged tissue expander breast
      reconstruction. METHODS: Thirty-five consecutive immediate implant-based breast
      reconstruction patients (62 breasts) and a matched group of 50 tissue expander
      immediate reconstruction patients (89 breasts) were identified. Normative data,
      complication rates, revision rates, number of office visits, total reconstructive
      time, and aesthetic outcomes were compared. RESULTS: Demographic variables and
      surgical risk factors were similar in both groups. At a mean follow-up of 14
      months, the overall complication rates were similar (p = 0.97), and the need for
      revision surgery was also similar (p = 0.94). Mean final implant volume did not
      differ between the two groups (397 +/- 93 cc for implants and 386 +/- 128 cc for
      expansion; p = 0.57). Mean number of office visits/time to nipple reconstruction
      was significantly different at 5.0 +/- 4 versus 9.2 +/- 3 visits (p < 0.001) and
      22 +/- 19 versus 43 +/- 24 weeks (p < 0.001) in the implant versus tissue
      expander group, respectively. Aesthetic evaluation revealed no significant
      differences. CONCLUSIONS: Immediate implant-based breast reconstruction has
      similar complication rates, need for revision, and aesthetic outcomes but fewer
      office visits and less reconstructive time when compared with tissue expander
      immediate breast reconstruction. In the appropriately selected patient, it is a
      safe option that provides similar outcomes in less time compared with staged
      expander-based reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      III.

PMID- 22634690
TI  - Expression of androgen, estrogen, progesterone, and growth hormone receptors in
      vascular malformations.
AB  - BACKGROUND: Vascular malformations frequently enlarge during adolescence,
      suggesting that hormones may be involved. The purpose of this study was to
      determine whether pubertal hormone receptors are present in vascular
      malformations and whether they differ from normal tissue. METHODS: Tissue
      specimens (arteriovenous malformation, lymphatic malformation, and venous
      malformation) were prospectively collected from patients undergoing resection.
      Immunohistochemistry was used to determine the presence of androgen, estrogen,
      progesterone, and growth hormone receptors. The effects of age, sex, location,
      and malformation type on receptor expression were analyzed. Age-, sex-, and
      location-matched normal tissues served as controls. RESULTS: Forty-five vascular
      malformation specimens were collected: arteriovenous malformation (n = 11),
      lymphatic malformation (n = 20), and venous malformation (n = 14). Growth hormone
      receptor expression was increased in arteriovenous malformation (72.7 percent),
      lymphatic malformation (65.0 percent), and venous malformation (57.1 percent)
      tissues compared with controls (25.8 percent) (p < 0.05). Growth hormone receptor
      was present primarily in the endothelium/perivasculature of malformations (93.1
      percent), whereas in normal tissue growth hormone receptor was located only in
      the stroma (p < 0.0001). Neither age, nor sex, nor location influenced receptor
      expression (p = 0.9). No differences in androgen receptor, estrogen receptor, and
      progesterone receptor staining were found between malformations and control
      samples (p = 0.7). CONCLUSIONS: Growth hormone receptor is overexpressed and
      principally located in the vessels of vascular malformations. Growth hormone
      might contribute to the expansion of vascular malformations.

PMID- 22634691
TI  - Therapeutic strategies in post-facial paralysis synkinesis in adult patients.
AB  - BACKGROUND: Facial synkinesis comprises unwanted facial muscle contractions in
      different facial muscle groups following voluntary ones, in cases of incomplete
      recovery from facial paralysis. Facial expressivity and function are impaired,
      and the psychological integrity of the patients is seriously affected. METHODS:
      Thirty-one adult patients (older than 18 years) presenting with post-facial
      paralysis synkinesis were included in this study. The mean patient age was 39.6
      years and the mean denervation time was 124 months. RESULTS: There were five
      patient groups. Group A (n = 9) underwent cross-facial nerve grafting and
      secondary microcoaptations. Group B (n = 8) had cross-facial nerve grafting,
      secondary microcoaptations, and botulinum toxin type A injections. Group C (n =
      6) received cross-facial nerve grafting, secondary microcoaptations, botulinum
      toxin type A, and selective neurectomies. Group D (n = 2) underwent cross-facial
      nerve grafting, direct muscle neurotization, and botulinum toxin type A. Group E
      underwent other means of treating synkinesis (n = 6), such as botulinum
      injections alone (n = 1), biofeedback alone (n = 2), biofeedback with selective
      neurectomies and myectomies (n = 2), and biofeedback and botulinum injections (n
      = 1). Group B had the highest synkinesis improvement (100 percent), followed by
      groups A and C (66 percent). Functional results were improved, with smile
      improvement being higher in group C and eye closure being higher in groups A, B,
      and E. CONCLUSION: Meticulous patient selection and evaluation followed by an
      individualized form of treatment, most frequently including cross-facial nerve
      grafting and secondary microcoaptations along with botulinum toxin type A and
      biofeedback including facial muscle retraining, constitute an effective and
      reliable methodology with which to combat post-facial paralysis synkinesis.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22634692
TI  - Bone biology and physiology: Part II. Clinical correlates.
AB  - The principles of bone biology and physiology permeate all subspecialty practices
      in plastic and reconstructive surgery, from hand surgery to aesthetic surgery.
      Despite its importance in our practices, these topics rarely surface within
      textbooks, literature reviews, or residency curricula. The authors present the
      second portion of a two-part review of the important concepts of bone biology and
      bone physiology relevant to plastic surgery, in an effort to ameliorate this
      educational gap.

PMID- 22634693
TI  - Does abdominoplasty have a positive influence on quality of life, self-esteem,
      and emotional stability?
AB  - BACKGROUND: In a previous prospective study, the authors evaluated the quality of
      life in patients undergoing aesthetic surgery. In this survey, the authors split
      up the operative indication and analyzed quality of life, self-esteem, and
      emotional stability after abdominoplasty alone. METHODS: Sixty-three patients
      participated in the study. The testing instrument consisted of a self-developed
      questionnaire to collect demographic and socioeconomic data and a postoperative
      complication questionnaire developed especially for abdominoplasties. In
      addition, a standardized self-assessment test on satisfaction and quality of life
      (Questions on Life Satisfaction), the Rosenberg Self -Esteem Questionnaire, and
      the Freiburg Personality Inventory were used. RESULTS: Significantly increasing
      values in some items of the standardized self-assessment test on satisfaction and
      quality of life were found: sum scores of the General Life Satisfaction showed a
      significant improvement (p = 0.004) and the scores of the items housing/living
      conditions (p = 0.000) and family life/children (p = 0.000). Within the
      Satisfaction with Health module, a significant improvement in the items mobility
      (p = 0.02) and independence from assistance (p = 0.01) was found. Values in the
      module Satisfaction with Appearance (Body Image) increased regarding satisfaction
      with the abdomen (p = 0.001). Over 84 percent were very satisfied with the
      aesthetic result, 93.4 percent would undergo the same treatment again, and 88.9
      percent would further recommend the operation. Data revealed that participants'
      self-esteem was very high and their emotional stability was very well balanced.
      CONCLUSIONS: This study demonstrates that abdominoplasty increases most aspects
      of quality of life, particularly family life, living conditions, mobility, and
      independency from assistance. Also, patient self-esteem and emotional stability
      ratings are very high postoperatively.

PMID- 22634694
TI  - Body contouring.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. List patient selection factors for body lift surgery. 2. Describe
      operative approaches for brachioplasty, upper body lift, abdominoplasty, lower
      body lift, and thigh lift. 3. Identify complications and pitfalls related to body
      lifting and describe how to avoid them. SUMMARY: The author discusses the
      preoperative assessment, surgical treatment plan, postoperative management,
      outcomes, and possible complications for a comprehensive spectrum of body
      contouring surgical procedures. Preoperative planning includes medical history
      and physical examination, along with an open discussion with the patient.
      Surgical procedures for brachioplasty, upper back lift, abdominoplasty, lower
      back lift, gluteal augmentation and thigh lift are discussed. Postoperative
      management pearls are shared, as well as pitfalls to be avoided.

PMID- 22634695
TI  - Methodologically rigorous clinical research.
AB  - BACKGROUND: Rigorous methodology increases the quality of clinical research by
      encouraging freedom from the biases inherent in clinical studies. As randomized
      controlled studies (clinical trial design) are rarely applicable to surgical
      research, the authors address the commonly used observational study designs and
      methodologies by presenting guidelines for rigor. METHODS: The authors performed
      a review of study designs, including cohort, case-control, and cross-sectional
      studies and case series/reports, and biases and confounders of study design.
      RESULTS: Details about biases and confounders at each study stage, study
      characteristics, rigor checklists, and published literature examples for each
      study design are summarized and presented in this report. CONCLUSIONS: For those
      surgeons interested in pursuing clinical research, mastery of the principles of
      methodologic rigor is imperative in the context of evidence-based medicine and
      widespread publication of clinical studies. Knowledge of the study designs and
      their appropriate application, and strict adherence to study design methods can
      provide high-quality evidence to serve as the basis for rational clinical
      decision-making.

PMID- 22634696
TI  - Assessing strength of evidence in diagnostic tests.
AB  - Clinical encounters between clinicians and patients begin with an attempt at
      diagnosis, a foundational element in determining a patient's ultimate outcome.
      Diagnosis that is expedient and accurate will result in a treatment that is
      expedient, appropriate, and cost-effective. In essence, evidence-based diagnosis
      is as vital as evidence-based intervention and treatment. If surgeons are
      committed to making expedient and accurate diagnoses, they must strive to apply
      diagnostic tests not just on the basis of ease, novelty, or availability but for
      the soundness of evidence behind them. In the scopes of both aesthetic and
      reconstructive surgery, advocating evidence-driven diagnostic test use is
      relevant. A pertinent example of how this relates to plastic surgery is the U.S.
      Food and Drug Administration recommendation to screen asymptomatic women with
      silicone breast implants with magnetic resonance imaging. For an important
      recommendation such as this that has tremendous cost implications to patients,
      sound study design and rigorous evaluation of the accuracy of magnetic resonance
      imaging as a screening tool has important health policy implications. The authors
      demonstrate how to determine the accuracy of diagnostic tests and, more
      importantly, illustrate the essential qualities of any study to establish the
      accuracy of a diagnostic test.

PMID- 22634697
TI  - Giant basal cell carcinoma: a series of 37 cases without metastasis.

PMID- 22634698
TI  - Thauera humireducens sp. nov., a humus-reducing bacterium isolated from a
      microbial fuel cell.
AB  - A Gram-negative, rod-shaped, non-spore-forming bacterium, designated SgZ-1(T),
      was isolated from the anode biofilm of a microbial fuel cell. The strain had the
      ability to grow under anaerobic condition via the oxidation of various organic
      compounds coupled to the reduction of anthraquione-2,6-disulfonate (AQDS) to
      anthrahydroquinone-2,6-disulfonate (AHQDS). Growth occurred in TSB in the
      presence of 0-5.5 % (w/v) NaCl (optimum 0-1 %), at 10-45  degrees C (optimum 25
      37  degrees C) and at pH 6.0-10.0 (optimum 8.0-8.5). Based on 16S rRNA gene
      sequence similarity, strain SgZ-1(T) belonged to the genus Thauera. The highest
      level of 16S rRNA gene sequences similarity (96.7 %) was found to be with Thauera
      aminoaromatica S2(T) and Thauera selenatis AX(T), and lower values were obtained
      when compared with other recognized Thauera species. Chemotaxonomic analysis
      revealed that strain SgZ-1(T) contained Q-8 as the predominant quinone, and
      putrescine and 2-hydroxyputrescine as the major polyamines. The major cellular
      fatty acids (>5 %) were C16 : 1omega6c and/or C16 : 1omega7c (44.6 %), C16 : 0
      (18.8 %), and C18 : 1omega6c and/or C18 : 1omega7c (12.7 %). Based on its
      phenotypic and phylogenetic properties, chemotaxonomic analysis and the results
      of physiological and biochemical tests, strain SgZ-1(T) ( = KACC 16524(T) = CCTCC
      M 2011497(T)) was designated the type strain of a novel species of the genus
      Thauera, for which the name Thauera humireducens sp. nov. was proposed.

PMID- 22634699
TI  - Bacillus gottheilii sp. nov., isolated from a pharmaceutical manufacturing site.
AB  - A novel Gram-staining-positive, rod-shaped, motile, strictly aerobic, endospore
      forming bacterium, designated WCC 4585(T), was isolated from a pharmaceutical
      production line. The organism grew optimally at 30  degrees C, at pH 8 and in the
      presence of 0.5 % (w/v) NaCl. Oval endospores were formed subterminally and
      terminally in swollen sporangia. The cell-wall diamino acid was meso
      diaminopimelic acid (type A1gamma) and the genomic DNA G+C content was 38.7 mol%.
      The major menaquinone was MK-7. The cellular fatty acid profile contained major
      amounts of iso-C15 : 0, anteiso-C15 : 0 and anteiso-C17 : 0, and the cellular
      phospholipids were diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine and aminophospholipid. The isolate was most closely
      related to Bacillus oceanisediminis H2(T), Bacillus infantis SMC 4352-1(T),
      Bacillus firmus NCIMB 9366(T), Bacillus circulans ATCC 4513(T) and Bacillus
      horneckiae DSM 23495(T) with which it shared less than 98.0 % 16S rRNA gene
      sequence similarity. DNA-DNA relatedness values between strain WCC 4585(T) and
      five type strains of related species were <=27 % and sequence similarity values
      based on groEL sequences were <=88.7 %. On the basis of the characteristics
      presented, strain WCC 4585(T) is proposed to represent a novel species, Bacillus
      gottheilii sp. nov. The type strain is WCC 4585(T)( = DSM 23668(T) = CCUG
      59876(T) = LMG 25856(T)).

PMID- 22634700
TI  - Micromonospora equina sp. nov., isolated from soil from a racecourse.
AB  - Two actinomycete strains were isolated from within the fynbos-rich area
      surrounded by the horseracing track at Kenilworth Racecourse in Cape Town, South
      Africa. Rapid molecular identification indicated that the isolates belonged to
      the family Micromonosporaceae. Based on 16S rRNA gene sequence blast analysis,
      the isolates were identified as members of the genus Micromonospora. Phylogenetic
      analysis showed that the isolates clustered with each other and were most closely
      related to Micromonospora viridifaciens DSM 43909(T). Further 16S rRNA gene
      sequence analysis using EzTaxon revealed that the isolates are closely related to
      Micromonospora auratinigra TT1-11(T), Micromonospora chaiyaphumensis MC5-1(T),
      Micromonospora eburnea LK2-10(T), Micromonospora nigra DSM 43818(T) and
      Micromonospora olivasterospora DSM 43868(T). DNA-DNA hybridization and
      physiological tests allowed genotypic and phenotypic differentiation of both
      isolates from related species; however, their high DNA-DNA relatedness showed
      that they belong to the same genomic species. Strain Y22(T) ( = DSM 45644(T) =
      NRRL B-24859(T)) was selected as the type strain to represent this novel species,
      for which the name Micromonospora equina sp. nov. is proposed.

PMID- 22634701
TI  - Flavobacterium enshiense sp. nov., isolated from soil, and emended descriptions
      of the genus Flavobacterium and Flavobacterium cauense, Flavobacterium
      saliperosum and Flavobacterium suncheonense.
AB  - A Gram-negative, strictly aerobic, yellow-pigmented rod, designated DK69(T), was
      isolated from soil collected from the waste liquid treatment facility of Bafeng
      Pharmaceutical Company in the city of Enshi, Hubei Province, China. Phylogenetic
      analysis based on 16S rRNA gene sequences placed strain DK69(T) in the genus
      Flavobacterium of the family Flavobacteriaceae. The highest 16S rRNA gene
      sequence similarities were found with Flavobacterium cauense R2A-7(T) (96.9 %),
      Flavobacterium saliperosum AS 1.3801(T) (96.3 %) and Flavobacterium suncheonense
      GH29-5(T) (95.7 %). The major fatty acids (>=5 %) were iso-C15 : 0, iso-C17 :
      1omega9c, C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 0 3-OH. The major polar lipids
      were phosphatidylethanolamine, one unidentified aminolipid and one unidentified
      lipid. The major respiratory quinone was menaquinone-6. The genomic DNA G+C
      content was 34.4 mol%. Strain DK69(T) represents a novel species of the genus
      Flavobacterium, for which the name Flavobacterium enshiense sp. nov. is proposed.
      The type strain is DK69(T) ( = CCTCC AB 2011144(T)  = KCTC 23775(T)). Emended
      descriptions of the genus Flavobacterium and Flavobacterium cauense,
      Flavobacterium saliperosum and Flavobacterium suncheonense are also proposed.

PMID- 22634702
TI  - Pseudonocardia antitumoralis sp. nov., a deoxynyboquinone-producing actinomycete
      isolated from a deep-sea sediment.
AB  - An aerobic actinomycete, designated SCSIO 01299(T), was isolated from a deep-sea
      sediment collected from the northern South China Sea at a depth of 3258 m. The
      isolate was found to be a natural producer of the synthesized antitumour agent
      deoxynyboquinone and its three new derivatives, pseudonocardians A, B and C. A
      blast search based on almost-complete 16S rRNA gene sequences showed that strain
      SCSIO 01299(T) had high sequence similarities with members of the genus
      Pseudonocardia. The 16S rRNA gene sequence phylogenetic tree revealed that strain
      SCSIO 01299(T) was a member of the genus Pseudonocardia. Phenotypic analysis,
      chemotaxonomy and DNA-DNA relatedness could readily distinguish the isolate from
      established members in this genus. It was concluded that strain SCSIO 01299(T)
      represents a novel species, for which the name Pseudonocardia antitumoralis sp.
      nov. is proposed. The type strain is SCSIO 01299(T) ( = DSM 45322(T)  = CCTCC M
      2011255(T)).

PMID- 22634703
TI  - Allonocardiopsis opalescens gen. nov., sp. nov., a new member of the suborder
      Streptosporangineae, from the surface-sterilized fruit of a medicinal plant.
AB  - An endophytic actinomycete, designated strain I10A-01259(T), was isolated from a
      surface-sterilized fruit of Lonicera maackii (Rupr.) Maxim., a medicinal plant,
      which was collected from a suburb of Beijing, China. Whole-cell hydrolysates of
      the isolate contained galactose and meso-diaminopimelic acid. The predominant
      phospholipids were phosphatidylglycerol and diphosphatidylglycerol; the
      menaquinones consisted mainly of MK-9, MK-11 and MK-12, with a minor amount of MK
      10. The major fatty acids were iso-C16 : 0, anteiso-C15 : 0 and iso-C15 : 0.
      Comparative analysis of 16S rRNA gene sequences indicated that strain I10A
      01259(T) was most closely related to Nocardiopsis arabia S186(T) (93.2 % sequence
      similarity), Thermobifida halotolerans YIM 90462(T) (93.0 %) and other strains of
      genera within the families Nocardiopsaceae and Thermomonosporaceae. On the
      phylogenetic tree based on 16S rRNA gene sequences, strain I10A-01259(T) fell
      within the radius of the suborder Streptosporangineae, in which the strain formed
      a distinct lineage next to the genera of the families Nocardiopsaceae and
      Thermomonosporaceae. Based on the data from our polyphasic taxonomic study, a
      novel genus and species, Allonocardiopsis opalescens gen. nov., sp. nov., are
      proposed within the suborder Streptosporangineae. The type strain of
      Allonocardiopsis opalescens is strain I10A-01259(T) ( = CPCC 203428(T)  = DSM
      45601(T)  = KCTC 19844(T)).

PMID- 22634704
TI  - Sediminibacterium ginsengisoli sp. nov., isolated from soil of a ginseng field,
      and emended descriptions of the genus Sediminibacterium and of Sediminibacterium
      salmoneum.
AB  - A Gram-negative bacterium, designated DCY13(T), was isolated from soil of a
      ginseng field in South Korea. Comparative analysis of 16S rRNA gene sequences
      showed that strain DCY13(T) shared the highest sequence similarity (95.0 %) with
      Sediminibacterium salmoneum NBRC 103935(T) and 87.6-91.4 % sequence similarity
      with other members of the family Chitinophagaceae. Cells were non-spore-forming
      rods, catalase- and oxidase-positive, motile by gliding and facultatively
      anaerobic. The only respiratory quinone was menaquinone 7 (MK-7) and the major
      fatty acids were iso-C17 : 0 3-OH, iso-C15 : 0 and iso-C15 : 1 G. The G+C content
      of the genomic DNA was 47.5+/-1.0 mol%. In addition to phosphatidylethanolamine,
      the major polar lipids were two unidentified aminophospholipids, one unidentified
      aminolipid and three unidentified polar lipids. The major cell-wall sugars were
      ribose, xylose and galactose. It is proposed that strain DCY13(T) represents a
      novel species in the genus Sediminibacterium, for which the name
      Sediminibacterium ginsengisoli sp. nov. is proposed. The type strain is DCY13(T)
      ( = KCTC 12833(T)  = JCM 15794(T)  = DSM 22335(T)). Emended descriptions of the
      genus Sediminibacterium and of Sediminibacterium salmoneum are also proposed.

PMID- 22634705
TI  - Chryseobacterium taihuense sp. nov., isolated from a eutrophic lake, and emended
      descriptions of the genus Chryseobacterium, Chryseobacterium taiwanense,
      Chryseobacterium jejuense and Chryseobacterium indoltheticum.
AB  - Bacterial strain THMBM1(T) was isolated from decomposing algal scum that was
      collected during an algal bloom in Lake Taihu, Wuxi City, Jiangsu Province,
      China. Cells of strain THMBM1(T) were Gram-negative, facultatively anaerobic, non
      motile rods. Colonies on tryptic soy agar were translucent and shiny with entire
      edges; yellow flexirubin-type pigments were produced. Growth was observed at 15
      45  degrees C (optimum 30-37  degrees C), at pH 5.0-9.0 (optimum pH 8.0) and in
      the presence of 0-4.0 % (w/v) NaCl (optimum 0-1.0 %). Strain THMBM1(T) contained
      MK-6 as the sole respiratory quinone and sym-homospermidine as the predominant
      polyamine. The predominant cellular fatty acids were iso-C15 : 0 (53.2 %), iso
      C17 : 0 3-OH (15.6 %) and iso-C17 : 1omega9c (11.9 %). The polar lipid profile
      consisted of phosphatidylethanolamine and five unidentified lipids. The DNA G+C
      content was 36.8 mol% (Tm). Strain THMBM1(T) was closely related to members of
      the genus Chryseobacterium, with 16S rRNA gene sequence similarities ranging from
      92.9 to 97.2 %, the highest sequence similarities being with Chryseobacterium
      taiwanense BCRC 17412(T) (97.2 %) and C. gambrini 5-1St1a(T) (97.1 %). DNA-DNA
      relatedness between strain THMBM1(T) and C. taiwanense JCM 21767(T) and C.
      gambrini DSM 18014(T) was 34.1  and 23.0 %, respectively. Based on these results,
      it is concluded that strain THMBM1(T) represents a novel species, for which the
      name Chryseobacterium taihuense sp. nov. is proposed. The type strain is
      THMBM1(T) ( = CGMCC 1.10941(T)  = NBRC 108747(T)). Emended descriptions of the
      genus Chryseobacterium and C. taiwanense, C. jejuense and C. indoltheticum are
      also proposed.

PMID- 22634706
TI  - Detection and classification of subject-generated artifacts in EEG signals using
      autoregressive models.
AB  - We examine the problem of accurate detection and classification of artifacts in
      continuous EEG recordings. Manual identification of artifacts, by means of an
      expert or panel of experts, can be tedious, time-consuming and infeasible for
      large datasets. We use autoregressive (AR) models for feature extraction and
      characterization of EEG signals containing several kinds of subject-generated
      artifacts. AR model parameters are scale-invariant features that can be used to
      develop models of artifacts across a population. We use a support vector machine
      (SVM) classifier to discriminate among artifact conditions using the AR model
      parameters as features. Results indicate reliable classification among several
      different artifact conditions across subjects (approximately 94%). These results
      suggest that AR modeling can be a useful tool for discriminating among artifact
      signals both within and across individuals.

PMID- 22634707
TI  - Surrogate-assisted analysis of weighted functional brain networks.
AB  - Graph-theoretical analyses of complex brain networks is a rapidly evolving field
      with a strong impact for neuroscientific and related clinical research. Due to a
      number of confounding variables, however, a reliable and meaningful
      characterization of particularly functional brain networks is a major challenge.
      Addressing this problem, we present an analysis approach for weighted networks
      that makes use of surrogate networks with preserved edge weights or vertex
      strengths. We first investigate whether characteristics of weighted networks are
      influenced by trivial properties of the edge weights or vertex strengths (e.g.,
      their standard deviations). If so, these influences are then effectively
      segregated with an appropriate surrogate normalization of the respective network
      characteristic. We demonstrate this approach by re-examining, in a time-resolved
      manner, weighted functional brain networks of epilepsy patients and control
      subjects derived from simultaneous EEG/MEG recordings during different behavioral
      states. We show that this surrogate-assisted analysis approach reveals
      complementary information about these networks, can aid with their
      interpretation, and thus can prevent deriving inappropriate conclusions.

PMID- 22634708
TI  - Th17 and regulatory T lymphocytes in primary biliary cirrhosis and systemic
      sclerosis as models of autoimmune fibrotic diseases.
AB  - Fibrotic autoimmune diseases are characterized by an inflammatory process in
      which fibrogenic cytokines, such as TGFbeta and IL6, have a major role.
      Interestingly, these cytokines are also involved in the generation and function
      of both an effector T lymphocyte subpopulation, the Th17 cells, and the
      regulatory T lymphocytes (Treg). These evidences raised the hypothesis that an
      unbalanced equilibrium induced by the overproduction of the fibrogenic cytokines
      may have pathogenic relevance in fibrotic autoimmune diseases. On this basis,
      this review analyzes the available data concerning Th17 and Treg generation and
      function in two representative fibrotic autoimmune diseases, primary biliary
      cirrhosis (PBC) and systemic sclerosis (SSc), as models for organ-specific and
      systemic diseases, respectively. With regard to the Th17 cells, their expansion
      was found to be a common feature associated with a relative contraction of Th1
      immune responses. Concerning to the regulatory T cell compartment, quantitative
      and qualitative alterations were observed in both diseases. However, while PBC
      patients showed defects only in the CD8+ Treg subset, SSc patients demonstrated
      abnormalities regarding to both the CD4+CD25+ and the CD8+ Treg subpopulations.
      Hence, the CD8+ Treg subset seems to be the most involved in the pathogenic
      cascade leading to fibrotic disease onset and maintenance. Collectively, the
      reviewed data support the concept that altered homeostasis between effector and
      regulatory T cell circuits is present in fibrotic autoimmune diseases and that
      the major factors responsible for such disequilibrium are Th17 cells in the
      effector arm and CD8+ Treg in the regulatory arm.

PMID- 22634710
TI  - Discrimination of genotoxic and non-genotoxic hepatocarcinogens by statistical
      analysis based on gene expression profiling in the mouse liver as determined by
      quantitative real-time PCR.
AB  - The general aim of the present study is to discriminate between mouse genotoxic
      and non-genotoxic hepatocarcinogens via selected gene expression patterns in the
      liver as analyzed by quantitative real-time PCR (qPCR) and statistical analysis.
      qPCR was conducted on liver samples from groups of 5 male, 9-week-old B6C3F(1)
      mice, at 4 and 48h following a single intraperitoneal administration of
      chemicals. We quantified 35 genes selected from our previous DNA microarray
      studies using 12 different chemicals: 8 genotoxic hepatocarcinogens (2
      acetylaminofluorene, 2,4-diaminotoluene, diisopropanolnitrosamine, 4
      dimethylaminoazobenzene, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, N
      nitrosomorpholine, quinoline and urethane) and 4 non-genotoxic hepatocarcinogens
      (1,4-dichlorobenzene, dichlorodiphenyltrichloroethane, di(2-ethylhexyl)phthalate
      and furan). A considerable number of genes exhibited significant changes in their
      gene expression ratios (experimental group/control group) analyzed statistically
      by the Dunnett's test and Welch's t-test. Finally, we distinguished between the
      genotoxic and non-genotoxic hepatocarcinogens by statistical analysis using
      principal component analysis (PCA) of the gene expression profiles for 7 genes
      (Btg2, Ccnf, Ccng1, Lpr1, Mbd1, Phlda3 and Tubb2c) at 4h and for 12 genes (Aen,
      Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Gdf15, Lrp1, Mbd1, Phlda3, Plk2 and Tubb2c) at
      48h. Seven major biological processes were extracted from the gene ontology
      analysis: apoptosis, the cell cycle, cell proliferation, DNA damage, DNA repair,
      oncogenes and tumor suppression. The major, biologically relevant gene pathway
      suggested was the DNA damage response pathway, resulting from signal transduction
      by a p53-class mediator leading to the induction of apoptosis. Eight genes (Aen,
      Bax, Btg2, Ccng1, Cdkn1a, Gdf15, Phlda3 and Plk2) that are directly associated
      with Trp53 contributed to the PCA. The current findings demonstrate a successful
      discrimination between genotoxic and non-genotoxic hepatocarcinogens, using qPCR
      and PCA, on 12 genes associated with a Trp53-mediated signaling pathway for DNA
      damage response at 4 and 48 h after a single administration of chemicals.

PMID- 22634711
TI  - Electroanalytical studies on green leaf volatiles for potential sensor
      development.
AB  - An electrochemical study for detecting green leaf plant volatiles from healthy
      and infected plants has been devised and tested. The electrocatalytic response of
      plant volatiles at a gold electrode was measured using cyclic voltammetry,
      amperometric current-time (i-t) analysis, differential pulse voltammetry (DPV)
      and hydrodynamic experiments. The sensitivity of the gold electrode in i-t
      analysis was 0.13 mA mM(-1) cm(-2) for cis-3-hexenol, 0.11 mA mM(-1) cm(-2) for
      cis-hexenyl acetate and 0.02 mA mM(-1) cm(-2) for hexyl acetate. The limits of
      detection of cis-3-hexenol, cis-hexenyl acetate and hexyl acetate by i-t analysis
      were 0.5, 0.3 and 0.6 MUM, respectively, at a signal to noise ratio of 3. The
      hydrodynamic studies yielded the electro-kinetic parameters such as diffusivities
      of plant volatiles in solution and the rate constants for their electrochemical
      reactions. The DPV and interference studies reveal that the gold electrode
      possessed high sensitivity for plant volatiles determination in synthetic
      samples, which imitates both healthy and infected plants.

PMID- 22634712
TI  - Order-parameter coupling in the improper ferroelectric lawsonite.
AB  - Low-temperature specific heat and thermal expansion measurements are used to
      study the hydrogen-based ferroelectric lawsonite over the temperature range 1.8 K
      <= T <= 300 K. The second-order phase transition near 125 K is detected in the
      experiments, and the low-temperature phase is determined to be improper
      ferroelectric and co-elastic. In the ferroelectric phase T <= 125 K, the
      spontaneous polarization P(s) is proportional to (1) the volume strain e(s), and
      (2) the excess entropy DeltaS(e). These proportionalities confirm the improper
      character of the ferroelectric phase transition. We develop a structural model
      that allows the off-centering of hydrogen positions to generate the spontaneous
      polarization. In the low-temperature limit we detect a Schottky anomaly (two
      level system) with an energy gap of Delta ~ 0.5 meV.

PMID- 22634715
TI  - A special focus issue on the materials of Prion 2011 meeting in Montreal, Canada.

PMID- 22634714
TI  - H3S10 phosphorylation by the JIL-1 kinase regulates H3K9 dimethylation and gene
      expression at the white locus in Drosophila.
AB  - The JIL-1 kinase is a multidomain protein that localizes specifically to
      euchromatin interband regions of polytene chromosomes and is the kinase
      responsible for histone H3S10 phosphorylation at interphase. Genetic interaction
      assays have suggested that the function of the epigenetic histone H3S10ph mark is
      to antagonize heterochromatization by participating in a dynamic balance between
      factors promoting repression and activation of gene expression as measured by
      position-effect variegation (PEV) assays. Interestingly, JIL-1 loss-of-function
      alleles can act either as an enhancer or indirectly as a suppressor of w(m4) PEV
      depending on the precise levels of JIL-1 kinase activity. In this study, we have
      explored the relationship between PEV and the relative levels of the H3S10ph and
      H3K9me2 marks at the white gene in both wild-type and w(m4) backgrounds by ChIP
      analysis. Our results indicate that H3K9me2 levels at the white gene directly
      correlate with its level of expression and that H3K9me2 levels in turn are
      regulated by H3S10 phosphorylation.

PMID- 22634716
TI  - The Creutzfeldt-Jakob Disease Foundation.
AB  - The Creutzfeldt-Jakob Disease (CJD) Foundation was formed in 1993 in Miami,
      Florida by two women who each lost a loved one to this terrible disease. They
      were instrumental in designing the Foundation's mission, which stresses a strong
      dedication to providing support and information to all affected families who turn
      to us for help. This mission continues to guide the Foundation's work today.

PMID- 22634717
TI  - Uptake of silver nanoparticles and toxicity to early life stages of Japanese
      medaka (Oryzias latipes): effect of coating materials.
AB  - Silver nanoparticles (AgNPs) with antimicrobial properties are perhaps the most
      deployed engineered nanomaterials in consumer products. Almost all AgNPs are
      coated with organic materials to enhance their dispersion in water. Contributions
      of coatings to the toxicity of NPs have received little attention. Studies using
      AgNPs with one of three different coating materials (citrate (Cit), gum arabic
      (GA), and polyvinylpyrrolidone (PVP)) showed significantly different toxicity. GA
      AgNP proved to be the most toxic, while PVP and Cit AgNP exhibited similar and
      lower toxicity. However, all AgNPs were about three to ten times less toxic than
      AgNO(3) when their toxicities were compared on a mass-concentration basis.
      Evidence for NP-specific toxicity was observed with longer time for initiation of
      toxicity and increased incidence of resultant spinal flexure of medaka exposed to
      AgNPs, compared to AgNO(3). Hyperspectral imaging of 6 MUm paraffin sections of
      fish exposed to AgNPs revealed AgNPs and their aggregates in tissues of fish.
      Gill distribution was ubiquitous, while small amounts were found in other organs,
      including the liver and brain. AgNPs were observed regularly in the gut lumen,
      but rarely in mural elements and mesentery. These results suggest that while
      ingestion was common, gills were the principal sites of AgNP uptake. In
      conclusion, AgNPs is a source of toxic Ag ions, while itself contribute partially
      to its toxicity to fish, and which interact with skin surface and were taken up
      via the gills.

PMID- 22634718
TI  - Liver X receptor regulates rheumatoid arthritis fibroblast-like synoviocyte
      invasiveness, matrix metalloproteinase 2 activation, interleukin-6 and CXCL10.
AB  - Fibroblast-like synoviocyte (FLS) invasiveness correlates with articular damage
      in rheumatoid arthritis (RA), yet little is known about its regulation. In this
      study we aimed to determine the role of the nuclear receptor liver X receptor
      (LXR) in FLS invasion. FLS were isolated from synovial tissues obtained from RA
      patients and from DA rats with pristane-induced arthritis. Invasion was tested on
      Matrigel-coated chambers in the presence of the LXR agonist T0901317, or control
      vehicle. FLS were cultured in the presence or absence of T0901317, and
      supernatants were used to quantify matrix metalloproteinase 1 (MMP-1), MMP-2, MMP
      3, interleukin-6 (IL-6), tumor necrosis factor-alpha and C-X-C motif chemokine
      ligand 10 (CXCL10). Nuclear factor-kappaB (NF-kappaB) (p65) and Akt activation,
      actin cytoskeleton, cell morphology and lamellipodia formation were also
      determined. The LXR agonist T0901317 significantly reduced DA FLS invasion by 99%
      (P <= 0.001), and RA FLS invasion by 96% (P <= 0.001), compared with control.
      T0901317-induced suppression of invasion was associated with reduced production
      of activated MMP-2, IL-6 and CXCL10 by RA FLS, and with reduction of actin
      filament reorganization and reduced polarized formation of lamellipodia. T0901317
      also prevented both IL-1beta-induced and IL-6-induced FLS invasion. NF-kappaB
      (p65) and Akt activation were not significantly affected by T0901317. This is the
      first description of a role for LXR in the regulation of FLS invasion and in
      processes and pathways implicated both in invasion as well as in inflammatory
      responses. These findings provide a new rationale for considering LXR agonists as
      therapeutic agents aimed at reducing both inflammation and FLS-mediated invasion
      and destruction in RA.

PMID- 22634719
TI  - Human "orchestrator" CD11b(+) B1 cells spontaneously secrete interleukin-10 and
      regulate T-cell activity.
AB  - Immune regulation produced by B cells has been attributed to production and
      secretion of interleukin (IL)-10, which is a characteristic of mouse B1 cells. In
      view of the widespread clinical use of B-cell depletion therapies in autoimmune
      and malignant diseases, it is important to monitor the function and fate of
      regulatory B cells. However, there is no consensus regarding the phenotypic
      identity of human IL-10(+) B cells. Here we show that human CD11b(+) B1 cells,
      one of two recently described subpopulations of B1 cells, spontaneously produce
      IL-10 and suppress T-cell activation. In view of the capacity of these B cells to
      either stimulate T-cell proliferation or suppress T-cell activation, CD11b(+) B1
      cells are considered to be capable of orchestrating elements of immune
      responsiveness and thus are termed "orchestrator B1 cells," or "B1orc," whereas
      CD11b(-) B1 cells that primarily secrete antibody are termed "secretor B1 cells,"
      or "B1sec."

PMID- 22634720
TI  - Activation of toll-like receptor 2 prevents suppression of T-cell interferon
      gamma production by modulating p38/extracellular signal-regulated kinase pathways
      following alcohol and burn injury.
AB  - Recent studies indicate that toll-like receptors (TLRs) are expressed on T cells
      and that these receptors directly or indirectly activate the adaptive immune
      system. We have shown previously that acute alcohol/ethanol (EtOH) intoxication
      combined with burn injury suppresses mesenteric lymph node (MLN) T-cell
      interleukin-2 (IL-2) and interferon gamma (IFN-gamma) production. We examined
      whether direct stimulation of T cells with TLR2, 4, 5 and 7 agonists modulates
      CD3-mediated T-cell IL-2/IFN-gamma release following EtOH and burn injury. Male
      mice were gavaged with EtOH (2.9 gm/kg) 4 h prior to receiving an ~12.5% total
      body surface area sham or full-thickness burn injury. Animals were killed on d 1
      after injury and T cells were purified from MLN and spleens. T cells were
      cultured with plate-bound anti-CD3 in the presence or absence of various TLR
      ligands. Although TLR2, 4 and 5 agonists potentiate anti-CD3-dependent IFN-gamma
      by T cells, the TLR2 agonist alone induced IFN-gamma production independent of
      CD3 stimulation. Furthermore, T cells were treated with inhibitors of myeloid
      differentiation primary response protein 88 (MyD88), TIR domain-containing
      adaptor protein (TIRAP), p38 and/or extracellular signal-regulated kinase (ERK)
      to determine the mechanism by which TLR2 mediates IL-2/IFN-gamma production. IL-2
      was not influenced by TLR agonists. MyD88 and TIRAP inhibitory peptides dose
      dependently diminished the ability of T cells to release IFN-gamma. p38 and ERK
      inhibitors also abolished TLR2-mediated T-cell IFN-gamma. Together, our findings
      suggest that TLR2 directly modulates T-cell IFN-gamma production following EtOH
      and burn injury, independent of antigen-presenting cells. Furthermore, we
      demonstrated that MyD88/TIRAP-dependent p38/ERK activation is critical to TLR2
      mediated T-cell IFN-gamma release following EtOH and burn injury.

PMID- 22634721
TI  - Initial assessment of the role of CXC chemokine receptor 4 after polytrauma.
AB  - CXC chemokine receptor (CXCR)-4 agonists have been shown to attenuate
      inflammation and organ injury in various disease models, including
      trauma/hemorrhage. The pathophysiological role of CXCR4 during the early response
      to tissue injury, however, remains unknown. Therefore, we investigated the
      effects of AMD3100, a drug that antagonizes binding of stromal cell-derived
      factor (SDF)-1alpha and ubiquitin to CXCR4 during the initial response to
      polytrauma in pigs. Fifteen minutes before polytrauma (femur fractures/lung
      contusion; control: sham), 350 nmol/kg AMD3100, equimolar AMD3100 and ubiquitin
      (350 nmol/kg each) or vehicle were administered intravenously. After a 60-min
      shock period, fluid resuscitation was performed for 360 min. Ubiquitin binding to
      peripheral blood mononuclear cells was significantly reduced after intravenous
      AMD3100. SDF-1alpha plasma levels increased transiently >10-fold with AMD3100 in
      all animals. In injured animals, AMD3100 increased fluid requirements to maintain
      hemodynamics and enhanced increases in peripheral blood granulocytes, lymphocytes
      and monocytes, compared with its effects in uninjured animals. Cytokine release
      from leukocytes in response to Toll-like receptor (TLR)-2 and TLR-4 activation
      was increased after in vitro AMD3100 treatment of normal whole blood and after in
      vivo AMD3100 administration in animals subjected to polytrauma. Coadministration
      of AMD3100/ubiquitin reduced lactate levels, prevented AMD3100-induced increases
      in fluid requirements and sensitization of the tumor necrosis factor (TNF)-alpha
      and interleukin (IL)-6 release upon TLR-2/4 activation, but did not attenuate
      increases in leukocyte counts and SDF-1alpha plasma levels. Our findings suggest
      that CXCR4 controls leukocyte mobilization after trauma, regulates leukocyte
      reactivity toward inflammatory stimuli and mediates protective effects during the
      early phase of trauma-induced inflammation.

PMID- 22634724
TI  - How many packing contacts are observed in protein crystals?
AB  - Most of the protein three-dimensional structures were determined with
      crystallographic methods in the solid state, where each molecule (therein after
      referred to as the "reference molecule") is surrounded by several other molecules
      that can influence its structure. The number of molecules that surround the
      reference molecule in protein crystal structures is examined on the basis of data
      extracted from the protein data bank. It is observed that there are as few as
      three and as many as 18 molecules in contact with the reference molecule, with an
      average number of about 10. The number of molecules around the reference molecule
      is smaller at higher symmetries than at lower symmetries and does not depend on
      the protein shape and dimension. The results reported here are a benchmark that
      may be useful the detection of potential anomalies and for the analyses of
      structural information both stored in databases or novel.

PMID- 22634723
TI  - HMGB1 mediates cognitive impairment in sepsis survivors.
AB  - Severe sepsis, a syndrome that complicates infection and injury, affects 750,000
      annually in the United States. The acute mortality rate is approximately 30%,
      but, strikingly, sepsis survivors have a significant disability burden: up to 25%
      of survivors are cognitively and physically impaired. To investigate the
      mechanisms underlying persistent cognitive impairment in sepsis survivors, here
      we developed a murine model of severe sepsis survivors following cecal ligation
      and puncture (CLP) to study cognitive impairments. We observed that serum levels
      of high mobility group box 1 (HMGB1), a critical mediator of acute sepsis
      pathophysiology, are increased in sepsis survivors. Significantly, these levels
      remain elevated for at least 4 wks after CLP. Sepsis survivors develop
      significant, persistent impairments in learning and memory, and anatomic changes
      in the hippocampus associated with a loss of synaptic plasticity. Administration
      of neutralizing anti-HMGB1 antibody to survivors, beginning 1 wk after onset of
      peritonitis, significantly improved memory impairments and brain pathology.
      Administration of recombinant HMGB1 to naive mice recapitulated the memory
      impairments. Together, these findings indicate that elevated HMGB1 levels mediate
      cognitive decline in sepsis survivors, and suggest that it may be possible to
      prevent or reverse cognitive impairments in sepsis survivors by administration of
      anti-HMGB1 antibodies.

PMID- 22634722
TI  - Expanding the clinical indications for alpha(1)-antitrypsin therapy.
AB  - alpha(1)-Antitrypsin (AAT) is a 52-kDa circulating serine protease inhibitor.
      Production of AAT by the liver maintains 0.9-1.75 mg/mL circulating levels.
      During acute-phase responses, circulating AAT levels increase more than fourfold.
      In individuals with one of several inherited mutations in AAT, low circulating
      levels increase the risk for lung, liver and pancreatic destructive diseases,
      particularly emphysema. These individuals are treated with lifelong weekly
      infusions of human plasma-derived AAT. An increasing amount of evidence appears
      to suggest that AAT possesses not only the ability to inhibit serine proteases,
      such as elastase and proteinase-3 (PR-3), but also to exert antiinflammatory and
      tissue-protective effects independent of protease inhibition. AAT modifies
      dendritic cell maturation and promotes T regulatory cell differentiation, induces
      interleukin (IL)-1 receptor antagonist and IL-10 release, protects various cell
      types from cell death, inhibits caspases-1 and -3 activity and inhibits IL-1
      production and activity. Importantly, unlike classic immunosuppressants, AAT
      allows undeterred isolated T-lymphocyte responses. On the basis of preclinical
      and clinical studies, AAT therapy for nondeficient individuals may interfere with
      disease progression in type 1 and type 2 diabetes, acute myocardial infarction,
      rheumatoid arthritis, inflammatory bowel disease, cystic fibrosis, transplant
      rejection, graft versus host disease and multiple sclerosis. AAT also appears to
      be antibacterial and an inhibitor of viral infections, such as influenza and
      human immunodeficiency virus (HIV), and is currently evaluated in clinical trials
      for type 1 diabetes, cystic fibrosis and graft versus host disease. Thus, AAT
      therapy appears to have advanced from replacement therapy, to a safe and
      potential treatment for a broad spectrum of inflammatory and immune-mediated
      diseases.

PMID- 22634725
TI  - Identification and structural characterization of two 14-3-3 binding sites in the
      human peptidylarginine deiminase type VI.
AB  - The regulation and function of peptidylarginine deiminase isoform VI (PAD6),
      which is a highly abundant protein associated with the cytoplasmic lattices in
      mammalian oocytes, is poorly understood so far. It has been shown previously,
      that 14-3-3 proteins, a class of regulatory adapter proteins ubiquitous in
      eukaryotes, bind to PAD6 in vivo in a phosphorylation dependent manner. Here we
      identify possible 14-3-3 binding sites in human PAD6 by in silico methods,
      looking for conserved, surface exposed serine residues. Two of these sites were
      confirmed as 14-3-3 binding sites by fluorescence polarization competition and X
      ray crystallography. We furthermore suggest a role of RSK-type kinases in the
      phosphorylation of one of these two binding sites and provide evidence in the
      form of in vitro kinase assays with p70S6 kinase and RSK1.

PMID- 22634726
TI  - Functional analysis of conserved cis- and trans-elements in the Hsp104 protein
      disaggregating machine.
AB  - Hsp104 is a double ring-forming AAA+ ATPase, which harnesses the energy of ATP
      binding and hydrolysis to rescue proteins from a previously aggregated state.
      Like other AAA+ machines, Hsp104 features conserved cis- and trans-acting
      elements, which are hallmarks of AAA+ members and are essential to Hsp104
      function. Despite these similarities, it was recently proposed that Hsp104 is an
      atypical AAA+ ATPase, which markedly differs in 3D structure from other AAA+
      machines. Consequently, it was proposed that arginines found in the non-conserved
      M-domain, but not the predicted Arg-fingers, serve the role of the critical trans
      acting element in Hsp104. While the structural discrepancy has been resolved, the
      role of the Arg-finger residues in Hsp104 remains controversial. Here, we
      exploited the ability of Hsp104 variants featuring mutations in one ring to
      retain ATPase and chaperone activities, to elucidate the functional role of the
      predicted Arg-finger residues. We found that the evolutionarily conserved Arg
      fingers are absolutely essential for ATP hydrolysis but are dispensable for
      hexamer assembly in Hsp104. On the other hand, M-domain arginines are not
      strictly required for ATP hydrolysis and affect the ATPase and chaperone
      activities in a complex manner. Our results confirm that Hsp104 is not an
      atypical AAA+ ATPase, and uses conserved structural elements common to diverse
      AAA+ machines to drive the mechanical unfolding of aggregated proteins.

PMID- 22634727
TI  - Theoretical investigation of quinone metabolites of dopamine interaction with DNA
      -insights into toxicological effects.
AB  - Dopamine (3,4-dihydroxyphenylethylamine, DA), an important neurotransmitter,
      exists in the cell bodies of the dopaminergic neurons of the substantia nigra.
      Oxidation of DA to its quinone and subsequent reaction with Adenine and Guanine
      in DNA result in the formation of depurinating adducts, thus causing DNA damage.
      In this article, we investigate the interaction of quinone metabolites of
      dopamine (DMQ) with models representing the structure of DNA using dispersion
      corrected density functional theory with an aim to evaluate the associated
      structural changes in DNA upon their interaction. Various binding sites for the
      DA metabolite on these DNA models have been considered and our computations on
      the activation barriers allowed us to identify preferential bonding sites for
      these metabolites analogous to experiments. Analysis of the geometry of these
      adducts in comparison to free base pairs reveals that the attack of DMQ causes
      remarkable changes in the structural properties. With our calculations, we
      propose that these structural alterations induce mutations by favoring the
      formation of depurinating adducts leading to mutagenic effects such as base
      mispairing, explaining the toxicological (carcinogenic and neurotoxic) behavior
      of DMQ.

PMID- 22634728
TI  - A non-canonical pathway for mammalian blue-green color vision.
AB  - The dynamic range of visual coding is extended by having separate ganglion cell
      types that respond to light increments and decrements. Although the primordial
      color vision system in mammals contains a well-characterized ganglion cell that
      responds to blue light increments (a blue On center cell), less is known about
      ganglion cells that respond to blue light decrements (blue Off center cells). We
      identified a regular mosaic of blue Off center ganglion cells in the ground
      squirrel. Contrary to the standard scheme, blue Off responses came from a blue On
      bipolar and inverting amacrine cell.

PMID- 22634729
TI  - The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in
      nociceptive neurons.
AB  - Nociceptors are a subset of small primary afferent neurons that respond to
      noxious chemical, thermal and mechanical stimuli. Ion channels in nociceptors
      respond differently to noxious stimuli and generate electrical signals in
      different ways. Anoctamin 1 (ANO1 also known as TMEM16A) is a Ca(2+)-activated
      chloride channel that is essential for numerous physiological functions. We found
      that ANO1 was activated by temperatures over 44  degrees C with steep heat
      sensitivity. ANO1 was expressed in small sensory neurons and was highly
      colocalized with nociceptor markers, which suggests that it may be involved in
      nociception. Application of heat ramps to dorsal root ganglion (DRG) neurons
      elicited robust ANO1-dependent depolarization. Furthermore, knockdown or deletion
      of ANO1 in DRG neurons substantially reduced nociceptive behavior in thermal pain
      models. These results indicate that ANO1 is a heat sensor that detects
      nociceptive thermal stimuli in sensory neurons and possibly mediates nociception.

PMID- 22634731
TI  - A color-coding amacrine cell may provide a blue-off signal in a mammalian retina.
AB  - Retinal amacrine cells are thought to lack chromatic or color-selective light
      responses and have only a minor role in color processing. We found that a type of
      mammalian (Ictidomys tridecemlineatus) amacrine cell selectively carries a blue
      On signal, which is received from a blue or short wavelength-sensitive (S) cone
      On bipolar cell. This glycinergic inhibitory S-cone amacrine cell is ideally
      placed for driving blue-Off responses in downstream ganglion cells.

PMID- 22634732
TI  - Thermal entanglement of a spin-1/2 Ising-Heisenberg model on a symmetrical
      diamond chain.
AB  - The entanglement quantum properties of a spin-1/2 Ising-Heisenberg model on a
      symmetrical diamond chain were analyzed. Due to the separable nature of the Ising
      type exchange interactions between neighboring Heisenberg dimers, calculation of
      the entanglement can be performed exactly for each individual dimer. Pairwise
      thermal entanglement was studied in terms of the isotropic Ising-Heisenberg model
      and analytical expressions for the concurrence (as a measure of bipartite
      entanglement) were obtained. The effects of external magnetic field H and next
      nearest neighbor interaction J(m) between nodal Ising sites were considered. The
      ground state structure and entanglement properties of the system were studied in
      a wide range of coupling constant values. Various regimes with different values
      of ground state entanglement were revealed, depending on the relation between
      competing interaction strengths. Finally, some novel effects, such as the two
      peak behavior of concurrence versus temperature and coexistence of phases with
      different values of magnetic entanglement, were observed.

PMID- 22634730
TI  - pHTomato, a red, genetically encoded indicator that enables multiplex
      interrogation of synaptic activity.
AB  - The usefulness of genetically encoded probes for optical monitoring of neuronal
      activity and brain circuits would be greatly advanced by the generation of
      multiple indicators with non-overlapping color spectra. Most existing indicators
      are derived from or spectrally convergent on GFP. We generated a bright, red, pH
      sensitive fluorescent protein, pHTomato, that can be used in parallel with green
      probes to monitor neuronal activity. SypHTomato, made by fusing pHTomato to the
      vesicular membrane protein synaptophysin, reported activity-dependent exocytosis
      as efficiently as green reporters. When expressed with the GFP-based indicator
      GCaMP3 in the same neuron, sypHTomato enabled concomitant imaging of transmitter
      release and presynaptic Ca(2+) transients at single nerve terminals. Expressing
      sypHTomato and GCaMP3 in separate cells enabled the simultaneous determination of
      presynaptic vesicular turnover and postsynaptic sub- and supra-threshold
      responses from a connected pair of neurons. With these new tools, we observed a
      close size matching between pre- and postsynaptic compartments, as well as
      interesting target cell-dependent regulation of presynaptic vesicle pools.
      Lastly, by coupling expression of pHTomato- and GFP-based probes with distinct
      variants of channelrhodopsin, we provided proof-of-principle for an all-optical
      approach to multiplex control and tracking of distinct circuit pathways.

PMID- 22634733
TI  - Xanthohumol suppresses inflammatory response to warm ischemia-reperfusion induced
      liver injury.
AB  - Liver ischemia/reperfusion (I/R) leads to formation of reactive oxygen species
      (ROS), which cause hepatic injury and initiate an inflammatory response, which is
      a critical problem after liver surgery and transplantation. Xanthohumol, the
      major prenylated chalcone found in hops, has been discussed for its anti
      inflammatory and ROS-scavenging properties, and thus, we aimed to investigate the
      effect of xanthohumol in a model of warm I/R liver injury. Xanthohumol was
      applied to BALB/c mice orally at a dose of 1 mg/g body weight for 5 days before
      I/R-injury was induced by clamping the vascular blood supply to the median and
      left lateral liver lobe for 1 h followed by a 6 h period of reperfusion. At this
      time, HPLC analysis revealed hepatic xanthohumol levels of approximately 2 MUM, a
      concentration which has been shown to inhibit inflammatory effects in vitro.
      Assessment of hepatic HMOX1 expression, hepatic glutathione content and
      immunohistochemical analysis for proteins conjugated with the reactive aldehyde 4
      hydroxynonenal indicated that I/R-induced oxidative stress was significantly
      inhibited in xanthohumol-fed compared to control mice. Histological analysis,
      TUNEL staining and determination of transaminase serum levels revealed no
      significant effects of xanthohumol on acute hepatocellular injury. However, at
      the same time point, pretreatment with xanthohumol almost completely blunted the
      I/R-induced AKT and NFkappaB activation and the expression of the proinflammatory
      genes IL-1alpha, IL-6, MCP-1 and ICAM-1, which are known to play a crucial role
      in the subacute phase of I/R-induced liver damage. In conclusion, these data
      indicate the potential of xanthohumol application to prevent adverse inflammatory
      responses to I/R-induced liver damage such as after surgical liver resection or
      transplantation.

PMID- 22634735
TI  - Mechanisms of action of thyroid hormones in the skeleton.
AB  - BACKGROUND: Thyroid hormones regulate skeletal development, acquisition of peak
      bone mass and adult bone maintenance. Abnormal thyroid status during childhood
      disrupts bone maturation and linear growth, while in adulthood it results in
      altered bone remodeling and an increased risk of fracture SCOPE OF REVIEW: This
      review considers the cellular effects and molecular mechanisms of thyroid hormone
      action in the skeleton. Human clinical and population data are discussed in
      relation to the skeletal phenotypes of a series of genetically modified mouse
      models of disrupted thyroid hormone signaling. MAJOR CONCLUSIONS: Euthyroid
      status is essential for normal bone development and maintenance. Major thyroid
      hormone actions in skeletal cells are mediated by thyroid hormone receptor alpha
      (TRalpha) and result in anabolic responses during growth and development but
      catabolic effects in adulthood. These homeostatic responses to thyroid hormone
      are locally regulated in individual skeletal cell types by the relative
      activities of the type 2 and 3 iodothyronine deiodinases, which control the
      supply of the active thyroid hormone 3,5,3'-L-triiodothyronine (T3) to its
      receptor. GENERAL SIGNIFICANCE: Population studies indicate that both thyroid
      hormone deficiency and excess are associated with an increased risk of fracture.
      Understanding the cellular and molecular basis of T3 action in skeletal cells
      will lead to the identification of new targets to regulate bone turnover and
      mineralization in the prevention and treatment of osteoporosis. This article is
      part of a Special Issue entitled Thyroid hormone signaling.

PMID- 22634734
TI  - The deiodinases and the control of intracellular thyroid hormone signaling during
      cellular differentiation.
AB  - BACKGROUND: Thyroid hormone influences gene expression in virtually all
      vertebrates. Its action is initiated by the activation of T4 to T3, an outer ring
      deiodination reaction that is catalyzed by the type 1 or the type 2 iodothyronine
      selenodeiodinases (D1 or D2). Inactivation of T4 and T3 occurs via inner ring
      deiodination catalyzed by the type 3 iodothyronine selenodeiodinases (D3). The T4
      concentration is generally quite stable in human plasma, with T3 levels also
      remaining constant. Deiodinase actions are tightly regulated in both pre- and
      post-natal life when they are required to make local adjustments of intracellular
      T3 concentrations in a precise spatio- and temporal manner. Although all the
      signals governing the dynamic expression of deiodinases in specific cell types
      are not known, many important regulatory factors have been deciphered. SCOPE OF
      REVIEW: This review provides striking examples from the recent literature
      illustrating how the expression of D2 and D3 is finely tuned during maturation of
      different organs, and how their action play a critical role in different settings
      to control intracellular T3 availability. MAJOR CONCLUSIONS: Emerging evidence
      indicates that in various cell contexts, D2 and D3 are expressed in a dynamic
      balance, in which the expression of one enzyme is coordinately regulated with
      that of the other to tightly control intracellular T3 levels commensurate with
      cell requirements at that time. GENERAL SIGNIFICANCE: Deiodinases control TH
      action in a precise spatio-temporal fashion thereby providing a novel mechanism
      for the local paracrine and autocrine regulation of TH action. This remarkable
      tissue-specific regulation of intracellular thyroid status remains hidden due to
      the maintenance of constant circulating TH concentrations by the hypothalamic
      pituitary-thyroid axis. This article is part of a Special Issue entitled Thyroid
      hormone signalling.

PMID- 22634737
TI  - Outcome of incidentally diagnosed pulmonary embolism in patients with malignancy.
AB  - PURPOSE OF REVIEW: With improvements in the quality of computed tomography (CT)
      examinations, pulmonary embolism is increasingly being detected incidentally in
      oncology patients undergoing routine cancer staging CT scans. The purpose of this
      review is to update current evidence on the prognosis of cancer patients
      diagnosed with incidental pulmonary embolism. RECENT FINDINGS: Several recent
      observational studies have shed some light on the prognostic implications of
      diagnosing incidental pulmonary embolism in cancer patients. In general,
      anticoagulant treatment is initiated in these patients. Even during treatment,
      recurrent venous thromboembolic events may occur with a frequency that is
      comparable to cancer patients who have symptomatic pulmonary embolism. It has
      been demonstrated that the diagnosis of incidental pulmonary embolism is
      associated with adverse survival in cancer patients, and the long-term mortality
      rate in incidental pulmonary embolism patients seems to approach that of
      symptomatic pulmonary embolism patients. SUMMARY: Overall, the body of literature
      on patients with incidental pulmonary embolism is sparse and does not allow firm
      recommendations on the therapeutic approach to these patients. Yet, in the
      absence of data on the natural clinical course of these patients, and the
      presence of cohort studies suggesting that incidental pulmonary embolism may
      impact recurrent venous thromboembolism and mortality, current consensus is to
      treat these patients in the same manner as symptomatic patients.

PMID- 22634736
TI  - The mechanism underlying nitroxyl and nitric oxide formation from hydroxamic
      acids.
AB  - BACKGROUND: The pharmacological effects of hydroxamic acids (RC(O)NHOH, HX) are
      partially attributed to their ability to serve as HNO and/or NO donors under
      oxidative stress. Given the development and use of HXs as therapeutic agents,
      elucidation of the oxidation mechanism is needed for more educated selection of
      HX-based drugs. METHODS: Acetohydroxamic and glycine-hydroxamic acids were
      oxidized at pH 7.0 by a continuous flux of radiolytically generated (.)OH or by
      metmyoglobin and H(2)O(2) reactions system. Gas chromatography and spectroscopic
      methods were used to monitor the accumulation of N(2)O, N(2), nitrite and
      hydroxylamine. RESULTS: Oxidation of HXs by (.)OH under anoxia yields N(2)O, but
      not nitrite, N(2) or hydroxylamine. Upon the addition of H(2)O(2) to solutions
      containing HX and metmyoglobin, which is instantaneously and continuously
      converted into compound II, nitrite and, to a lesser extent, N(2)O are
      accumulated under both anoxia and normoxia. CONCLUSIONS: Oxidation of HXs under
      anoxia by a continuous flux of (.)OH, which solely oxidizes the hydroxamate
      moiety to RC(O)NHO(.), forms HNO. This observation implies that bimolecular
      decomposition of RC(O)NHO(.) competes efficiently with unimolecular decomposition
      processes such as internal disproportionation, hydrolysis or homolysis. Oxidation
      by metmyoglobin/H(2)O(2) involves relatively mild oxidants (compounds I and II).
      Compound I reacts with HX forming RC(O)NHO(.) and compound II, which oxidizes HX,
      RC(O)NHO(.), HNO and NO. The latter reaction is the main source of nitrite.
      GENERAL SIGNIFICANCE: HXs under oxidative stress release HNO, but can be
      considered as NO-donors provided that HNO oxidation is more efficient than its
      reaction with other biological targets.

PMID- 22634739
TI  - Quantitative cardiovascular magnetic resonance perfusion imaging: inter-study
      reproducibility.
AB  - AIMS: To evaluate the inter-study reproducibility of quantitative cardiovascular
      magnetic resonance (CMR) myocardial perfusion imaging and the influence of
      diurnal variation on perfusion. Data on these are limited, despite being
      crucially important for performing serial examinations both in clinical practice
      and in trials. METHODS AND RESULTS: Sixteen healthy volunteers underwent high
      resolution 3 T perfusion imaging three times during a single day to evaluate
      inter-study reproducibility and the effects of diurnal variation. Absolute
      perfusion was determined in each coronary artery territory and globally by Fermi
      constrained deconvolution of myocardial signal intensity curves. Left ventricular
      (LV) volumes and function were also calculated. Eleven full data sets were
      suitable for quantitative perfusion analysis. Global rest and stress perfusion
      and myocardial perfusion reserve (MPR) were 0.6 +/- 0.1 and 2.5 +/- 0.5 mL/min/g
      and 4.3 +/- 0.9, respectively, for the first scan and were 0.5 +/- 0.2 and 2.1 +/
      0.5 mL/min/g and 4.2 +/- 1.2 for the second (P= 0.1, 0.19, and 0.37,
      respectively). Inter-study reproducibility was moderate. The coefficient of
      variation (CV) was 16.0, 26.8, and 23.9% for global rest and stress perfusion and
      MPR, respectively. The corresponding territorial CVs were 27.5, 35.2, and 33.5%.
      The reproducibility of LV volumes and function was excellent (CV 4, 7.7, and 4.6%
      for end-diastolic volume, end-systolic volume, and ejection fraction,
      respectively). There were no significant detectable diurnal variations in
      perfusion or LV volumes and function (P>= 0.05 for all). CONCLUSION: The inter
      study reproducibility of quantitative myocardial perfusion is reasonable and best
      for global rest perfusion. No significant diurnal variation in perfusion was
      observed.

PMID- 22634740
TI  - Diffuse myocardial fibrosis in severe aortic stenosis: an equilibrium contrast
      cardiovascular magnetic resonance study.
AB  - AIMS: Haemodynamics alone do not fully explain symptoms and prognosis in
      clinically severe aortic stenosis (AS). Myocardial disease, specifically diffuse
      myocardial fibrosis (DMF), may contribute. We used equilibrium contrast
      cardiovascular magnetic resonance (EQ-CMR) and sought to non-invasively measure
      DMF in severe AS and determine its clinical significance before and after valve
      replacement. METHODS AND RESULTS: Patients with severe AS underwent
      echocardiography, brain natriuretic peptide (BNP), 6 min walk test (6MWT), and EQ
      CMR pre- (n = 63) at baseline and at 6 months post- (n = 42) aortic valve
      replacement (AVR). EQ-CMR was also performed in 30 normal controls. Baseline:
      patients with AS had more DMF than controls (18 vs. 13%, P = 0.007) with a wide
      range (5-38%) that overlapped controls. The extent of diffuse fibrosis correlated
      inversely with the 6MWT performance (r(2) = 0.22, P = 0.001). Those with severe
      diastolic dysfunction had more DMF (P = 0.01). On multivariable analysis, the
      predictors of performance at 6MWT were diffuse fibrosis and BNP (P = 0.003 and
      0.02, respectively). Post-op: following valve replacement, morphological and
      functional parameters improved [6 MWT, LA area, BNP, left ventricular (LV)
      hypertrophy, and volumes]. LV hypertrophy regression was shown to be cell volume
      reduction (P < 0.001) and not fibrosis regression (P = 0.54). Of the five deaths
      over six-month follow-up, four occurred in patients in the highest tertile of
      DMF. CONCLUSION: DMF as measured by EQ-CMR is elevated in severe AS vs. normal
      controls but with a considerable overlap. It correlates with functional capacity
      at baseline. LV hypertrophy regression 6 months after AVR is cellular rather than
      fibrosis resolution.

PMID- 22634741
TI  - A qualitative approach using the integrative model of behaviour change to
      identify intervention strategies to increase optimal child restraint practices
      among culturally and linguistically diverse families in New South Wales.
AB  - OBJECTIVES: To qualitatively explore barriers to optimal child restraint use
      using the integrative behaviour change model in culturally and linguistically
      diverse (CALD) communities in New South Wales (NSW), Australia. METHODS: A semi
      structured discussion was used to conduct 11 language specific focus groups in
      Arabic, Assyrian, Cantonese, Mandarin, Vietnamese and Turkish. Translated
      transcriptions were analysed using the major concepts of the integrative
      behaviour change model. RESULTS: Restraint use intent among CALD community carers
      is related to perceived safety of their children and complying with the law.
      While most participants appreciated the safety benefits of correct and
      appropriate use, a minority did not. Child restraint legislation may positively
      influence social norms, and enforcement appears to increase parental self
      efficacy. However, concerns over child comfort may negatively influence both
      norms and self-efficacy. There are clear deficits in knowledge that may act as
      barriers as well as confusion over best practice in safely transporting children.
      Large family size, vehicle size and cost appear to be real environmental
      constraints in CALD communities. CONCLUSION: Determinants of intent and deficits
      in knowledge in this diverse range of CALD communities in NSW Australia are
      similar to those reported in other qualitative studies regardless of the
      population studied. This indicates that key messages should be the same
      regardless of the target population. However, for CALD communities there is a
      specific need to ensure access to detailed information through appropriate
      delivery strategies and languages. Furthermore, practical constraints such as
      cost of restraints and family size may be particularly important in CALD
      communities.

PMID- 22634742
TI  - Differences in incidence of injury between rural and urban children in Canada and
      the USA: a systematic review.
AB  - OBJECTIVE: The goal of the study was to systematically review available evidence
      regarding differences in injury incidence between rural and urban paediatric
      populations in Canada and the USA. DATA SOURCE: Eight electronic databases,
      institutional websites and reference lists of relevant studies including
      published and unpublished reports. SELECTION CRITERIA: Population-based
      observational studies or surveys published from 1970 to February 2011 that
      compared injury incidence or injury-related healthcare outcomes between rural and
      urban children (<18) living in Canada or the USA. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently applied selection criteria and assessed
      methodological quality of studies. Data were extracted by one author and
      independently verified by the second author. Injury rate ratios for rural and
      urban children were extracted or calculated. Data were synthesised descriptively
      due to substantial heterogeneity among studies. RESULTS: A total of 41 studies
      were included for this review (seven surveys and 34 studies using administrative
      health databases). Internal validity of included studies was moderate. Rural
      children were at higher risk of overall injury, motor vehicle crash injury and
      suicide, whereas urban children in the USA experienced higher rates of firearm
      related homicides. Greater rural-urban injury disparities were likely to be found
      between more extreme rural and urban areas. In particular, children in remote
      rural areas are at increased risk of severe injuries than urban counterparts.
      Overall, healthcare costs per child for injury were higher for rural children.
      CONCLUSION: These findings indicate the need of developing geographic area
      specific injury-prevention strategies. Future research is required to investigate
      rural-urban disparity for less-studied injuries and related health outcomes (eg,
      disability). Systematic review registration number CRD42011001244 (PROSPERO
      2011).

PMID- 22634743
TI  - Quantum entanglement and criticality of the antiferromagnetic Heisenberg model in
      an external field.
AB  - By Lanczos exact diagonalization and the infinite time-evolving block decimation
      (iTEBD) technique, the two-site entanglement as well as the bipartite
      entanglement, the ground state energy, the nearest-neighbor correlations, and the
      magnetization in the antiferromagnetic Heisenberg (AFH) model under an external
      field are investigated. With increasing external field, the small size system
      shows some distinct upward magnetization stairsteps, accompanied synchronously
      with some downward two-site entanglement stairsteps. In the thermodynamic limit,
      the two-site entanglement, as well as the bipartite entanglement, the ground
      state energy, the nearest-neighbor correlations, and the magnetization are
      calculated, and the critical magnetic field h(c) = 2.0 is determined exactly. Our
      numerical results show that the quantum entanglement is sensitive to the subtle
      changing of the ground state, and can be used to describe the magnetization and
      quantum phase transition. Based on the discontinuous behavior of the first-order
      derivative of the entanglement entropy and fidelity per site, we think that the
      quantum phase transition in this model should belong to the second-order
      category. Furthermore, in the magnon existence region (h < 2.0), a
      logarithmically divergent behavior of block entanglement which can be described
      by a free bosonic field theory is observed, and the central charge c is
      determined to be 1.

PMID- 22634744
TI  - Groundwater resources in Brazil: a review of possible impacts caused by climate
      change.
AB  - Groundwater has a strategic role in times of climate change mainly because
      aquifers can provide water for long periods, even during very long and severe
      drought. The reduction and/or changes on the precipitation pattern can diminish
      the recharge mainly in unconfined aquifer, causing available groundwater
      restriction. The expected impact of long-term climate changes on the Brazilian
      aquifers for 2050 will lead to a severe reduction in 70% of recharge in the
      Northeast region aquifers (comparing to 2010 values), varying from 30% to 70% in
      the North region. Data referring to the South and Southeast regions are more
      favorable, with an increase in the relative recharge values from 30% to 100%.
      Another expected impact is the increase in demand and the decrease in the surface
      water availability that will make the population turn to aquifers as its main
      source of water for public or private uses in many regions of the country. Thus,
      an integrated use of surface and groundwater must therefore be considered in the
      water use planning. The solution of water scarcity is based on three factors:
      society growth awareness, better knowledge on the characteristics of hydraulic
      and chemical aquifers and effective management actions.

PMID- 22634746
TI  - Signal transduction in Plasmodium-Red Blood Cells interactions and in
      cytoadherence.
AB  - Malaria is responsible for more than 1.5 million deaths each year, especially
      among children (Snow et al. 2005). Despite of the severity of malaria situation
      and great effort to the development of new drug targets (Yuan et al. 2011) there
      is still a relative low investment toward antimalarial drugs. Briefly there are
      targets classes of antimalarial drugs currently being tested including: kinases,
      proteases, ion channel of GPCR, nuclear receptor, among others (Gamo et al.
      2010). Here we review malaria signal transduction pathways in Red Blood Cells
      (RBC) as well as infected RBCs and endothelial cells interactions, namely
      cytoadherence. The last process is thought to play an important role in the
      pathogenesis of severe malaria. The molecules displayed on the surface of both
      infected erythrocytes (IE) and vascular endothelial cells (EC) exert themselves
      as important mediators in cytoadherence, in that they not only induce structural
      and metabolic changes on both sides, but also trigger multiple signal
      transduction processes, leading to alteration of gene expression, with the
      balance between positive and negative regulation determining endothelial
      pathology during a malaria infection.

PMID- 22634747
TI  - Production, characterization and application of inulinase from fungal endophyte
      CCMB 328.
AB  - Inulinase (beta-2,1-D- fructan fructanohydrolase), EC 3.2.1.7, targets the beta
      2,1 linkage of inulin, a polyfructan consisting of linear beta-2,1 linked
      fructose, and hydrolyzes it into fructose. This use provides an alternative to
      produce fructose syrup through the hydrolysis of inulin. The objective of this
      work was to study the production, characterization and applications of inulinases
      from the fungal endophyte CCMB 328 isolated from the Brazilian semi-arid region.
      Response Surface Methodology (RSM) was employed to evaluate the effect of
      variables (concentration of glucose and yeast extract), on secreted inulinase
      activities detected in the culture medium and also in the inulin hydrolysis. The
      results showed that the best conditions for inulinase production by CCMB 328 are
      9.89 g / L for glucose and 1.09 g / L for yeast extract. The concentration of
      0.20 mol/L of NaCl and KCl increased the activity of inulinase from CCMB 328 by
      approximately 63% and 37%, respectively. The results also showed that the
      inulinase has potential for inulin hydrolysis, whose conversion yields roughly
      72.48 % for an initial concentration of inulin at 1% (w/v).

PMID- 22634748
TI  - Cloning and expression analysis of two ROR-gamma homologues (ROR-gammaa1 and ROR
      gammaa2) in rainbow trout Oncorhynchus mykiss.
AB  - This paper describes the cloning and characterisation of two retinoid-related
      orphan receptor (ROR)-gamma homologues (ROR-gammaa1 and -gammaa2) in rainbow
      trout (Oncorhynchus mykiss). The coding region predicted for both homologues
      consists of 1410 base pairs (bp), which translate into two 469 amino acid (aa)
      proteins. The trout ROR-gammas revealed a high conservation of both DNA- and
      ligand-binding domains (functional regions of the nuclear receptor family), and
      shared a high homology to mammalian ROR-gammat. A phylogenetic tree containing
      ROR family members confirmed that both trout homologues clustered within the ROR
      gamma group. Both results suggested that these molecules are likely to be ROR
      gamma homologues, more similar to the mammalian splice variant ROR-gammat than
      the full length ROR-gamma. Expression analysis of tissues obtained from healthy
      fish revealed highest constitutive expression of trout ROR-gamma in muscle,
      followed by the brain, heart and skin. This suggests that these genes may play an
      important role in such tissues. In vitro studies, using trout cell lines,
      demonstrated that ROR-gamma is induced significantly by LPS and down-regulated by
      the presence of PolyI:C and recombinant interferon (IFN)-gamma. Moreover,
      analysis of this gene in head kidney macrophages and mixed primary leucocyte
      cultures indicated that differences were apparent between the different cell
      types/sources used, indicating that its expression may be cell-type dependent.
      Additional studies to investigate the regulation of this gene in vivo
      demonstrated that its expression was significantly higher in vaccinated vs
      unvaccinated fish following bacterial (Yersinia ruckeri) challenge but it was
      down-regulated after a viral (VHSV) infection. This suggests a potential role of
      trout ROR-gamma, a putative T(H)17 transcription factor, in protection against
      extracellular bacteria.

PMID- 22634749
TI  - Characterization and evaluation of sex-specific expression of suppressors of
      cytokine signaling (SOCS)-1 and -3 in juvenile yellow perch (Perca flavescens)
      treated with lipopolysaccharide.
AB  - The suppressor of cytokine signaling (SOCS) proteins are a family of
      intracellular proteins that are centrally involved with vertebrate growth,
      development and immunity via their effects as negative feed-back regulators of
      cytokine (and hormone) signaling. The genes for SOCS-1 & -3 were cloned,
      sequences analyzed and expression patterns examined in the commercially-important
      teleost, yellow perch (Perca flavescens). The deduced (mature) proteins for
      yellow perch (yp)SOCS-1 and (yp)SOCS-3 consist of 211 and 205 amino acids,
      respectively. Functional domains such as the Src homology-2 (SH2) and SOCS-box
      were present in ypSOCS-1 and ypSOCS-3 and these domains were well conserved
      between teleost species. Sequence analysis showed that ypSOCS-1 & -3 share
      highest homology (among similar teleost sequences), to the stickleback
      (Gasterosteus aculatus) SOCS-1 & -3 protein homologs. To investigate sex-specific
      expression of the ypSOCS-1 and ypSOCS-3 mRNAs, juvenile male and female yellow
      perch were immunologically challenged with a single injection (10 MUg/g bw) of
      lipopolysaccharide (LPS) and tissues (gill, head kidney, kidney, liver and
      spleen) were sampled over a 48-h time-course. Quantitative real-time PCR analysis
      showed that ypSOCS-1 & -3 were expressed in all tissues examined and at all
      sampling time-points. LPS injection significantly induced ypSOCS-1 & -3 mRNA
      levels in gill, head kidney, liver, kidney and spleen, with maximal induction
      occurring at 6 h post-injection in each tissue. By 48-h post-injection,
      expression levels for ypSOCS-1 & -3 mRNAs approached, or reached, control levels
      in all tissues examined. While there were statistical interactions among
      variables (treatment, time and sex) for ypSOCS-1, we only found a main effect of
      sex on SOCS-3 mRNA expression in head kidney with higher copy numbers occurring
      in males than in females treated with LPS. Sexually-dimorphic expression of SOCS
      1 or -3 mRNA has not been examined, or described, in a teleost. Our findings
      suggest the involvement of the SOCS genes in the yellow perch immune response and
      that differences among the sexes are evident and should be explored further.

PMID- 22634750
TI  - The preparation of highly ordered TiO2 nanotube arrays by an anodization method
      and their applications.
AB  - The tubular-shaped nanostructure of TiO(2) is very interesting, and highly
      ordered arrays of TiO(2) nanotubes (TNTs) can be easily fabricated by anodization
      of the Ti substrate in specific electrolytes. Here in this feature article, we
      review synthesis methods for various TNTs including normal, alloy, and
      architectural forms such as bamboos, lace, and flowers. Specific nanosize
      architectures such as bamboo and lace types can be regulated by alternating
      voltage and further anodizing. In order to extend light response of TNTs to
      visible solar spectra, various dopings of specific elements have been discussed.
      The normal and modified TNTs are suggested for applications such as dye
      sensitized solar cells, water splitting, photocatalytic degradation of
      pollutants, CO(2) reduction, sensors, energy storage devices including Li ion
      batteries and supercapacitors, and other applications such as flexible substrate
      and biomaterials.

PMID- 22634751
TI  - Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome.
AB  - IMAGe syndrome (intrauterine growth restriction, metaphyseal dysplasia, adrenal
      hypoplasia congenita and genital anomalies) is an undergrowth developmental
      disorder with life-threatening consequences. An identity-by-descent analysis in a
      family with IMAGe syndrome identified a 17.2-Mb locus on chromosome 11p15 that
      segregated in the affected family members. Targeted exon array capture of the
      disease locus, followed by high-throughput genomic sequencing and validation by
      dideoxy sequencing, identified missense mutations in the imprinted gene CDKN1C
      (also known as P57KIP2) in two familial and four unrelated patients. A familial
      analysis showed an imprinted mode of inheritance in which only maternal
      transmission of the mutation resulted in IMAGe syndrome. CDKN1C inhibits cell
      cycle progression, and we found that targeted expression of IMAGe-associated
      CDKN1C mutations in Drosophila caused severe eye growth defects compared to wild
      type CDKN1C, suggesting a gain-of-function mechanism. All IMAGe-associated
      mutations clustered in the PCNA-binding domain of CDKN1C and resulted in loss of
      PCNA binding, distinguishing them from the mutations of CDKN1C that cause
      Beckwith-Wiedemann syndrome, an overgrowth syndrome.

PMID- 22634752
TI  - Manipulating nucleosome disfavoring sequences allows fine-tune regulation of gene
      expression in yeast.
AB  - Understanding how precise control of gene expression is specified within
      regulatory DNA sequences is a key challenge with far-reaching implications. Many
      studies have focused on the regulatory role of transcription factor-binding
      sites. Here, we explore the transcriptional effects of different elements,
      nucleosome-disfavoring sequences and, specifically, poly(dA:dT) tracts that are
      highly prevalent in eukaryotic promoters. By measuring promoter activity for a
      large-scale promoter library, designed with systematic manipulations to the
      properties and spatial arrangement of poly(dA:dT) tracts, we show that these
      tracts significantly and causally affect transcription. We show that manipulating
      these elements offers a general genetic mechanism, applicable to promoters
      regulated by different transcription factors, for tuning expression in a
      predictable manner, with resolution that can be even finer than that attained by
      altering transcription factor sites. Overall, our results advance the
      understanding of the regulatory code and suggest a potential mechanism by which
      promoters yielding prespecified expression patterns can be designed.

PMID- 22634753
TI  - Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial
      glucocorticoid deficiency.
AB  - Using targeted exome sequencing, we identified mutations in NNT, an antioxidant
      defense gene, in individuals with familial glucocorticoid deficiency. In mice
      with Nnt loss, higher levels of adrenocortical cell apoptosis and impaired
      glucocorticoid production were observed. NNT knockdown in a human adrenocortical
      cell line resulted in impaired redox potential and increased reactive oxygen
      species (ROS) levels. Our results suggest that NNT may have a role in ROS
      detoxification in human adrenal glands.

PMID- 22634754
TI  - Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma.
AB  - To survey hepatitis B virus (HBV) integration in liver cancer genomes, we
      conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative
      hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV
      integration is observed more frequently in the tumors (86.4%) than in adjacent
      liver tissues (30.7%). Copy-number variations (CNVs) were significantly increased
      at HBV breakpoint locations where chromosomal instability was likely induced.
      Approximately 40% of HBV breakpoints within the HBV genome were located within a
      1,800-bp region where the viral enhancer, X gene and core gene are located. We
      also identified recurrent HBV integration events (in >= 4 HCCs) that were
      validated by RNA sequencing (RNA-seq) and Sanger sequencing at the known and
      putative cancer-related TERT, MLL4 and CCNE1 genes, which showed upregulated gene
      expression in tumor versus normal tissue. We also report evidence that suggests
      that the number of HBV integrations is associated with patient survival.

PMID- 22634756
TI  - Whole-genome sequencing of liver cancers identifies etiological influences on
      mutation patterns and recurrent mutations in chromatin regulators.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death
      worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which
      were associated with hepatitis B or C virus infections, including two sets of
      multicentric tumors. Although no common somatic mutations were identified in the
      multicentric tumor pairs, their whole-genome substitution patterns were similar,
      suggesting that these tumors developed from independent mutations, although their
      shared etiological backgrounds may have strongly influenced their somatic
      mutation patterns. Statistical and functional analyses yielded a list of
      recurrently mutated genes. Multiple chromatin regulators, including ARID1A,
      ARID1B, ARID2, MLL and MLL3, were mutated in ~50% of the tumors. Hepatitis B
      virus genome integration in the TERT locus was frequently observed in a high
      clonal proportion. Our whole-genome sequencing analysis of HCCs identified the
      influence of etiological background on somatic mutation patterns and subsequent
      carcinogenesis, as well as recurrent mutations in chromatin regulators in HCCs.

PMID- 22634757
TI  - Oscillatory activity in the subthalamic nucleus during arm reaching in
      Parkinson's disease.
AB  - Oscillatory activities in the brain within the beta (15-30 Hz) and gamma (70-90
      Hz) ranges have been implicated in the generation of voluntary movement. However,
      their roles remain unclear. Here, we record local field potential activity from
      the region of the subthalamic nucleus during movement of the contralateral limb
      in 11 patients with Parkinson's disease. Patients were on their normal
      dopaminergic medication and were cued to perform arm-reaching movements after a
      delay period at three different speeds: 'slow', 'normal', and 'fast'. Beta
      activity desynchronized earlier in response to the cue indicating an upcoming
      fast reach than to the cues for slow or normal speed movement. There was no
      difference in the degree of beta desynchronization between reaching speeds and
      beta desynchronization was established prior to movement onset in all cases. In
      contrast, synchronization in the gamma range developed during the reaching
      movement, and was especially pronounced during fast reaching. Thus the timing of
      suppression in the beta band depended on task demands, whereas the degree of
      increase in gamma oscillations depended on movement speed. These findings point
      to functionally segregated roles for different oscillatory frequencies in motor
      preparation and performance.

PMID- 22634758
TI  - Inhibition of ROS-induced p38MAPK and ERK activation in microglia by acupuncture
      relieves neuropathic pain after spinal cord injury in rats.
AB  - Acupuncture (AP) is currently used worldwide to relieve pain. However, little is
      known about its mechanisms of action. We found that after spinal cord injury
      (SCI), AP inhibited the production of superoxide anion (O(2).), which acted as a
      modulator for microglial activation, and the analgesic effect of AP was
      attributed to its anti-microglial activating action. Direct injection of a ROS
      scavenger inhibited SCI-induced NP. After contusion injury which induces the
      below-level neuropathic pain (NP), Shuigou and Yanglingquan acupoints were
      applied. AP relieved mechanical allodynia and thermal hyperalgesia, while vehicle
      and simulated AP did not. AP also decreased the proportion of activated
      microglia, and inhibited both p38MAPK and ERK activation in microglia at the L4
      5. Also, the level of prostaglandin E(2) (PGE2), which is produced via ERK
      signaling and mediates the below-level pain through PGE2 receptor, was reduced by
      AP. Injection of p38MAPK or ERK inhibitors attenuated NP and decreased PGE2
      production. Furthermore, ROS produced after injury-induced p38MAPK and ERK
      activation in microglia, and mediated mechanical allodynia and thermal
      hyperalgesia, which were inhibited by AP or a ROS scavenger. AP also inhibited
      the expression of inflammatory mediators. Therefore, our results suggest that the
      analgesic effect of AP may be partly mediated by inhibiting ROS-induced
      microglial activation and inflammatory responses after SCI and provide the
      possibility that AP can be used effectively as a non-pharmacological intervention
      for SCI-induced chronic NP in patients.

PMID- 22634759
TI  - Transposase-derived proteins FHY3/FAR1 interact with PHYTOCHROME-INTERACTING
      FACTOR1 to regulate chlorophyll biosynthesis by modulating HEMB1 during
      deetiolation in Arabidopsis.
AB  - Successful chlorophyll biosynthesis during initial light exposure is critical for
      plant survival and growth, as excess accumulation of chlorophyll precursors in
      darkness can cause photooxidative damage to cells. Therefore, efficient
      mechanisms have evolved to precisely regulate chlorophyll biosynthesis in plants.
      Here, we identify FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and FAR-RED IMPAIRED
      RESPONSE1 (FAR1), two transposase-derived transcription factors, as positive
      regulators of chlorophyll biosynthesis in Arabidopsis thaliana. We show that null
      mutations in FHY3 and FAR1 cause reduced protochlorophyllide (a precursor of
      chlorophyll) levels in darkness and less photobleaching in the light. We find
      that FHY3 directly binds to the promoter and activates expression of HEMB1, which
      encodes 5-aminolevulinic acid dehydratase in the chlorophyll biosynthetic
      pathway. We reveal that PHYTOCHROME-INTERACTING FACTOR1 physically interacts with
      the DNA binding domain of FHY3, thereby partly repressing FHY3/FAR1-activated
      HEMB1 expression. Strikingly, FHY3 expression is upregulated by white light. In
      addition, our genetic data indicate that overexpression, severe reduction, or
      lack of HEMB1 impairs plant growth and development. Together, our findings reveal
      a crucial role of FHY3/FAR1 in regulating chlorophyll biosynthesis, thus
      uncovering a new layer of regulation by which light promotes plant dark-light
      transition in early seedling development.

PMID- 22634760
TI  - Transcriptome-wide changes in Chlamydomonas reinhardtii gene expression regulated
      by carbon dioxide and the CO2-concentrating mechanism regulator CIA5/CCM1.
AB  - We used RNA sequencing to query the Chlamydomonas reinhardtii transcriptome for
      regulation by CO(2) and by the transcription regulator CIA5 (CCM1). Both CO(2)
      and CIA5 are known to play roles in acclimation to low CO(2) and in induction of
      an essential CO(2)-concentrating mechanism (CCM), but less is known about their
      interaction and impact on the whole transcriptome. Our comparison of the
      transcriptome of a wild type versus a cia5 mutant strain under three different
      CO(2) conditions, high CO(2) (5%), low CO(2) (0.03 to 0.05%), and very low CO(2)
      (<0.02%), provided an entry into global changes in the gene expression patterns
      occurring in response to the interaction between CO(2) and CIA5. We observed a
      massive impact of CIA5 and CO(2) on the transcriptome, affecting almost 25% of
      all Chlamydomonas genes, and we discovered an array of gene clusters with
      distinctive expression patterns that provide insight into the regulatory
      interaction between CIA5 and CO(2). Several individual clusters respond primarily
      to either CIA5 or CO(2), providing access to genes regulated by one factor but
      decoupled from the other. Three distinct clusters clearly associated with CCM
      related genes may represent a rich source of candidates for new CCM components,
      including a small cluster of genes encoding putative inorganic carbon
      transporters.

PMID- 22634761
TI  - PHO2-dependent degradation of PHO1 modulates phosphate homeostasis in
      Arabidopsis.
AB  - The Arabidopsis thaliana pho2 mutant, which is defective in a ubiquitin
      conjugating E2 enzyme, displays inorganic phosphate (Pi) toxicity as a result of
      enhanced uptake and root-to-shoot translocation of Pi. To elucidate downstream
      components of the PHO2-dependent regulatory pathway, we identified two pho2
      suppressors as carrying missense mutations in PHO1, which has been implicated in
      Pi loading to the xylem. In support of the genetic interaction between PHO1 and
      PHO2, we found that the protein level of PHO1 is increased in pho2, whereas such
      accumulation is ameliorated in both pho2 suppressors. Results from cycloheximide
      and endosomal Cys protease inhibitor E-64d treatments further suggest that PHO1
      degradation is PHO2 dependent and involves multivesicular body-mediated vacuolar
      proteolysis. Using the transient expression system of tobacco (Nicotiana tabacum)
      leaves, we demonstrated that PHO1 and PHO2 are partially colocalized and
      physically interact in the endomembranes, where the ubiquitin conjugase activity
      of PHO2 is required for PHO1 degradation. In addition, reduced PHO1 expression
      caused by PHO1 mutations impede Pi uptake, indicating a functional association
      between xylem loading and acquisition of Pi. Together, our findings uncover a
      pivotal molecular mechanism by which PHO2 modulates the degradation of PHO1 in
      the endomembranes to maintain Pi homeostasis in plants.

PMID- 22634762
TI  - The essential role of the N-terminal domain of the orange carotenoid protein in
      cyanobacterial photoprotection: importance of a positive charge for phycobilisome
      binding.
AB  - Most cyanobacteria, under high light conditions, decrease the amount of energy
      arriving at the reaction centers by increasing thermal energy dissipation at the
      level of the phycobilisome, the extramembranous antenna. This mechanism is
      induced by photoactivation of the Orange Carotenoid Protein (OCP). To identify
      how the activated OCP interacts with phycobilisomes (PBs), several OCP mutants
      were constructed, and the influence of mutations on photoactivity, stability, and
      binding to PBs was characterized. The disruption of the salt bridge between
      Arg155 and Glu244, which stabilizes the interaction between the N- and C-terminal
      domains, increased the rate of photoactivity and the stability of the
      photoactivated OCP, suggesting that the activated OCP has an open structure with
      decreased interdomain interaction. Changing Glu244 to leucine had no effect on
      OCP binding to PBs. By contrast, substitution of Arg155 with a neutral or a
      negatively charged amino acid largely decreased OCP binding to the PBs, whereas
      substitution with a lysine slightly perturbed the interaction. These results
      strongly suggest that the surface of the N-terminal domain, containing the
      Arg155, interacts with the PB and that the positive charge of Arg155 plays a key
      role in photoprotection.

PMID- 22634755
TI  - Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer
      risk.
AB  - We performed a meta-analysis of five genome-wide association studies to identify
      common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases
      and 9,649 controls. Replication analysis was performed in case-control sets
      totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci
      at 6p21 (rs1321311, near CDKN1A; P = 1.14 * 10(-10)), 11q13.4 (rs3824999,
      intronic to POLD3; P = 3.65 * 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P =
      7.30 * 10(-10)) This brings the number of independent loci associated with CRC
      risk to 20 and provides further insight into the genetic architecture of
      inherited susceptibility to CRC.

PMID- 22634763
TI  - Chimeric FLS2 receptors reveal the basis for differential flagellin perception in
      Arabidopsis and tomato.
AB  - The flagellin receptor of Arabidopsis thaliana, At-FLAGELLIN SENSING2 (FLS2), has
      become a model for mechanistic and functional studies on plant immune receptors.
      Here, we started out with a comparison of At-FLS2 and the orthologous tomato
      (Solanum lycopersicum) receptor Sl-FLS2. Both receptors specifically responded to
      picomolar concentrations of the genuine flg22 ligand but proved insensitive to
      >10(6)-fold higher concentrations of CLV3 peptides that have recently been
      reported as a second type of ligand for At-FLS2. At-FLS2 and Sl-FLS2 exhibit
      species-specific differences in the recognition of shortened or sequence-modified
      flg22 ligands. To map the sites responsible for these species-specific traits on
      the FLS2 receptors, we performed domain swaps, substituting subsets of the 28
      leucine-rich repeats (LRRs) in At-FLS2 with the corresponding LRRs from Sl-FLS2.
      We found that the LRRs 7 to 10 of Sl-FLS2 determine the high affinity of Sl-FLS2
      for the core part RINSAKDD of flg22. In addition, we discovered importance of the
      LRRs 19 to 24 for the responsiveness to C-terminally modified flagellin peptides.
      These results indicate that ligand perception in FLS2 is a complex molecular
      process that involves LRRs from both the outermost and innermost LRRs of the FLS2
      ectodomain.

PMID- 22634766
TI  - Comments from the editor.

PMID- 22634767
TI  - Improved needle visualization with electronic beam steering: proof of concept.
AB  - PURPOSE: The objective of this study was to evaluate electronic beam steering to
      improve needle visualization. METHODS: Various needles ranging from 27 to 12
      gauge were evaluated with a modified CX50 (Philips Ultrasound, Bothell, Wash)
      using a 12-MHz linear probe. For proof of concept, the needles were placed in a
      pork roast at various random angles. The ultrasound beam was electronically
      steered at angles from 0 to 50 degrees. Images were obtained at the various
      angles and compared. Two patients undergoing a thyroid biopsy, one patient
      undergoing biopsy of the supraclavicular node, and one undergoing a breast biopsy
      were evaluated using electronic beam steering at various angles. The images were
      stored and subjectively compared. RESULTS: All needles were better visualized
      when the ultrasound beam was steered as close to perpendicular to the needle as
      possible. Significant improvements in needle including tip visualization by
      subjective visual inspection were found by applying the appropriate beam angle.
      CONCLUSIONS: Electronic beam steering has the potential to significantly improve
      needle visualization.

PMID- 22634764
TI  - Activation of the carbon concentrating mechanism by CO2 deprivation coincides
      with massive transcriptional restructuring in Chlamydomonas reinhardtii.
AB  - A CO(2)-concentrating mechanism (CCM) is essential for the growth of most
      eukaryotic algae under ambient (392 ppm) and very low (<100 ppm) CO(2)
      concentrations. In this study, we used replicated deep mRNA sequencing and
      regulatory network reconstruction to capture a remarkable scope of changes in
      gene expression that occurs when Chlamydomonas reinhardtii cells are shifted from
      high to very low levels of CO(2) (<=100 ppm). CCM induction 30 to 180 min post
      CO(2) deprivation coincides with statistically significant changes in the
      expression of an astonishing 38% (5884) of the 15,501 nonoverlapping C.
      reinhardtii genes. Of these genes, 1088 genes were induced and 3828 genes were
      downregulated by a log(2) factor of 2. The latter indicate a global reduction in
      photosynthesis, protein synthesis, and energy-related biochemical pathways. The
      magnitude of transcriptional rearrangement and its major patterns are robust as
      analyzed by three different statistical methods. De novo DNA motif discovery
      revealed new putative binding sites for Myeloid oncogene family transcription
      factors potentially involved in activating low CO(2)-induced genes. The (CA)(n)
      repeat (9 <= n <= 25) is present in 29% of upregulated genes but almost absent
      from promoters of downregulated genes. These discoveries open many avenues for
      new research.

PMID- 22634768
TI  - Nongynecologic findings on pelvic ultrasound: focus on gastrointestinal diseases.
AB  - Ultrasound (US) is considered the first-line imaging modality of choice in women
      presenting with pelvic complaints. Although imaging is focused on detecting
      abnormalities of the uterus and adnexa, occasionally nongynecologic findings are
      detected, which may or may not explain the patient's symptoms. Many of these
      findings are related to the gastrointestinal (GI) tract. Although most of these
      GI abnormalities are better diagnosed with computed tomography (CT), symptoms are
      often nonspecific and US may be the first imaging modality requested by referring
      clinicians. Sonographers should be aware of the possibility of nongynecologic
      diseases in patients with pelvic symptoms, particularly if US evaluation of the
      female reproductive tract does not provide an answer to the clinical question.
      Careful attention to the bowel when performing a pelvic US may allow the
      sonographer to diagnose GI pelvic diseases such as appendicitis, diverticulitis,
      colitis, bowel obstruction, mesenteric adenitis, epiploic appendagitis, Crohn
      disease, and even GI malignancy. As concerns grow regarding the radiation dose of
      pelvic CT, the use of iodinated contrast material, and imaging costs, US
      examination may be increasingly requested as an initial imaging study in patients
      in whom GI diseases is primarily suspected in the pelvis, and familiarity with
      the various sonographic manifestations will aid considerably in establishing the
      correct diagnosis.

PMID- 22634789
TI  - Fibrous pseudotumor of the testis: case 1.

PMID- 22634790
TI  - Intraductal papillary mucinous neoplasm.

PMID- 22634791
TI  - Pneumoperitoneum.

PMID- 22634792
TI  - Sonographic appearance of rotator cuff tears.

PMID- 22634793
TI  - Hypertrophied anterior division of ascending pharyngeal artery simulating
      internal carotid artery.

PMID- 22634794
TI  - Tuberculous epididymitis.

PMID- 22634796
TI  - Commentary on American College of Radiology Appropriateness Criteria.

PMID- 22634795
TI  - ACR Appropriateness Criteria(r) Multiple gestations.
AB  - Multiple gestations are high-risk compared with singleton pregnancies.
      Prematurity and intrauterine growth restrictions are the major sources of
      morbidity and mortality common to all twin gestations. Monochorionic twins are at
      a higher risk for twin-twin transfusion, fetal growth restriction, congenital
      anomalies, vasa previa, velamentous insertion of the umbilical cord and fetal
      death. Therefore, determination of multiple gestation, amnionicity and
      chorionicity in the first trimester is important. Follow up examinations to
      evaluate fetal well-being include assessment of fetal growth and amniotic fluid
      volume, umbilical artery Doppler, nonstress test and biophysical profile. To
      date, there is a paucity of literature regarding imaging schedules for follow-up.
      At the very least, antepartum testing in multiple gestations is recommended in
      all situations in which surveillance would ordinarily be performed in a singleton
      pregnancy.The ACR Appropriateness Criteria are evidence-based guidelines for
      specific clinical conditions that are reviewed biennially 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 procedures by the panel. In those instances where
      evidence is lacking or not definitive, expert opinion may be used to recommend
      imaging.

PMID- 22634798
TI  - The design of a contextualized responsive evaluation framework for fishery
      management in Benin.
AB  - The main question addressed by this article is how to adapt the responsive
      evaluation (RE) approach to an intervention context characterized by repetition
      of ineffective interventions, ambiguous intervention action theories among
      stakeholders, and high complexity. The context is Grand-Popo, a fishing
      municipality located on Benin's southwest Atlantic coast. The fishery management
      interventionists and the fishing communities in the municipality all espoused
      concern for the sustainable improvement of fishing actors' livelihood conditions,
      but differed about the reasons for this livelihood impairment, and about what
      should be done, when, where, and by whom. Given this ambiguity, we identified RE
      as a promising action research approach to facilitate dialogue and mutual
      learning, and consequently to improve stakeholders' ability to resolve problems.
      However, this approach seems to have some shortcomings in the Grand-Popo context,
      regarding the repetitive ineffectiveness of interventions, high complexity, and
      uncertainty. Therefore, based on our empirical study, we add three dimensions to
      the existing RE framework: historical analysis to deal with routine
      interventions, exploration and discussion of incongruities of action theories to
      trigger double-loop learning, and system analysis to deal with complexity and
      uncertainty. This article does not intend to address the implications or impact
      of this adapted RE framework. Instead, we suggest some criteria and indicators
      for evaluating whether the proposed amended RE approach has assisted in resolving
      the fishery problems in Grand-Popo after the approach has been applied.

PMID- 22634799
TI  - Bevacizumab plus irinotecan in recurrent malignant glioma shows high overall
      survival in a multicenter retrospective pooled series of the Spanish Neuro
      Oncology Research Group (GEINO).
AB  - There is no 'standard of care' for recurrent malignant glioma (MG). Our aim is to
      confirm the efficacy and safety of bevacizumab 10 mg/kg plus irinotecan 125 mg/m2
      (or 340 mg/m2 if enzyme-inducing antiepileptic drugs) every 2 weeks for a maximum
      of 1 year in a retrospective pooled series of patients with recurrent MG. The
      inclusion criteria were as follows: age 18 years and above, histology of MG,
      progression after radiation and temozolomide, Karnofsky performance status (KPS)
      of at least 60, and signed informed consent for bevacizumab compassionate use.
      Response was assessed by MRI using the Macdonald criteria and evaluation of the
      FLAIR sequence every 8 weeks. A total of 130 patients were enrolled; 72% had
      glioblastoma (GBM). The median age of the patients was 53 years (20-78); the
      median KPS was 80%; the median number of prior chemotherapy lines was 2 (1-5);
      the median interval between the diagnosis of MG and inclusion was 14.6 months (2
      166); and the median number of bevacizumab infusions was 8 (1-39). The median
      follow-up duration was 7.2 months (1-47). The median overall survival (OS) was
      8.8 months for GBM and 11.2 months for anaplastic glioma (AG). The median
      progression-free survival was 5.1 months for GBM and 4.6 months for AG. The
      response rate was 56% for GBM and 68% for AG. Neurological and KPS improvements
      were observed in 49 and 45% of patients. Only KPS less than 80% was associated
      with a worse significant response rate (odds ratio, 0.57; 95% confidence
      interval, 0.22-0.96). The most frequent grades 3-4 toxicities were asthenia (7%),
      diarrhea (6%), and thromboembolic events (5%). There were five toxic deaths (4%).
      Bevacizumab plus irinotecan in recurrent MG improves responses, progression-free
      survival, and OS compared with historical data. KPS of at least 80% was a
      predictive factor for response and OS.

PMID- 22634800
TI  - Crystal electric field in the R2Ti2O7 pyrochlore compounds.
AB  - Using a simple scaling law, a unique set of crystal-field parameters for the rare
      earth ions R in the R(2)Ti(2)O(7) pyrochlore series is shown to provide a proper
      description of the crystal-field excitations previously observed by neutron
      scattering. The two spectroscopic g factors are given for the compounds with
      doublet ground states, as well as the ground-state wavefunctions for all the
      compounds.

PMID- 22634801
TI  - [Social support and health: standpoints from the social and human sciences].
AB  - This article analyses the themes and conceptual-theoretical approaches of the
      social support in the literature from important international journals about
      social sciences and medicine, and in from 1983 to 2005 are analyzed. 259
      international and 57 national abstracts was reading for the identification and
      computing the relations of the social support with health/disease/care. A deeper
      conceptual analysis about social support and the theories of social science were
      reported in an intentional sample of 56 international and 18 national texts. The
      international literature is based on the social psychology, in the several trends
      of the sociology and of the political science and less in the anthropology. The
      national literature dialogues less with the psychosocial theories and more with
      the sociological and anthropological theories. In this latter literature the
      social support approaches are concerned with social network theories;
      reciprocity, exchanges and cultural values. It is concluded that different trends
      guide the conceptual-theoretical analyses of the social support, being the
      international literature older, wider, more diversified and empirical, but with
      scarce anthropological production. The national literature is more reflexive them
      empirical.

PMID- 22634802
TI  - [An anthropological contribution to social support].

PMID- 22634803
TI  - [Social support and health: contributions of the social and human sciences to
      health interventions].

PMID- 22634805
TI  - [Social support network and health of elderly individuals with chronic
      pneumopathies].
AB  - This study sought to analyze characteristics of the social support network of the
      elderly with chronic pneumopathies, establishing links with health
      maintenance/rehabilitation. The assumptions of Social Network Analysis (SNA)
      methodology were used, addressing the social support concept. A questionnaire and
      semi-structured interviews, both applied to 16 elderly people attended by a
      public hospital in Fortaleza-CE, were used for data collection. Quantitative data
      were processed using the UCINET 6.123, NetDraw 2.38 and Microsoft Excel software
      programs. In the qualitative analysis, the body of material was subjected to
      interpretations based on relevant and current theoretical references. Each
      informant brought an average of 10.37 individuals into the network. Among the 3
      types of social support, there was a predominance of informational support given
      by health professionals. The importance of reciprocity in providing/receiving
      social support was also noted, as well as the participation of health
      professionals and the family functioning as social support. The conclusion
      reached was that the network of the elderly with pneumopathies is not cohesive,
      being restricted to the personal network of each individual, and that even so,
      the informants recognize and are satisfied with the social support it provides.

PMID- 22634806
TI  - ["Being home away from home": vulnerability, religiosity and social support among
      Brazilian migrants in Japan].
AB  - This paper analyzes the role of religiosity and the impact of social support in
      the lives of Brazilian migrants in Japan. Despite being in Japan for over two
      decades, the Brazilians are not integrated into the local society. This social
      alienation has a negative effect on the health of the migrants, making them prone
      to mental and physical distress. The lack of language skills prevents the
      migrants from looking for professional help, and even if they seek for it they
      cannot express themselves properly. In this context, the migrants found support
      among their compatriots and religious groups. This essay is based on ethnographic
      research carried out in Japan between 2003 and 2006 and focuses on the work and
      activities of the Catholics among the Brazilian migrants. The data collection was
      based on 15 semi-structured interviews, which were conducted among the members.
      Besides the religious support, the group offers the migrants a social support
      space for their daily lives in Japan. Therefore, the group represents a place of
      socialization and social support for many Brazilians, which helps them to
      overcome their feelings of vulnerability. The ecclesiastic power, on the other
      hand, regulates the migrants' behavior through an ethos and a world view
      legitimized by the group.

PMID- 22634807
TI  - [Matricial support in workers' health: creating networks in primary care in the
      Unified Health System (SUS), the case of Amparo in the state of Sao Paulo].
AB  - The Reference Center in Workers' Health of Amparo in the State of Sao Paulo
      promotes actions directed to workers' health in primary care. In order to
      understand the process, we conducted research in Matricial Support in Workers'
      Health, its trajectory, difficulties and potential, using a qualitative case
      study approach. The main matricial support activities are thematic meetings,
      informative bulletins and systematic support. The exchange of knowledge and
      experience leads to a closer bond between the professionals. Horizontal technical
      support brings about a reorganization of work in health, mutual responsibility
      for cases and a new outlook on illness by integrating assistance and surveillance
      actions. An excess workload, rotation of health professionals, undernotification
      of Work-Related Accidents and Diseases and regional organization are the
      challenges to be tackled. Matricial Support in Workers' Health is strategic for
      the insertion of such actions in primary care and represents a step forward in
      the reorientation of the assistential medical model, with the introduction of the
      work-health relationship in family health.

PMID- 22634808
TI  - [The meaning of the performance of the Family Health Strategy team in a socially
      vulnerable community].
AB  - This study sought to understand the meaning of the performance of a Family Health
      Strategy team in a socially vulnerable community. Grounded Data Theory was used
      as a methodological benchmark and the data collection technique consisted of
      interviews with twenty-five Family Health Strategy professionals between July and
      December of 2009. Data analysis revealed that the Family Health Strategy can be
      seen as a facilitator and stimulator of the process of expansion and
      consolidation of healthcare networks. They represent a new approach in community
      intervention, by viewing the human being as a multi-dimensional and singular
      being, inserted in his/her real context. A new assistential model is essentially
      being developed by the reorganization of healthcare practices, assisted by the
      multiplicity of complex relationships, interactions and associations that occur
      within the social and family context.

PMID- 22634809
TI  - [Profile of the elderly individual dependent on home care in low socioeconomic
      level communities in Porto Alegre in the state of Rio Grande do Sul].
AB  - The scope of this study was to estimate the prevalence of home care and to
      identify the demographic, socioeconomic, behavioral and health profile of
      dependent elderly individuals. The cross-sectional and representative delineation
      of the communities of Restinga and Extremo Sul in Porto Alegre in the State of
      Rio Grande do Sul included 638 elderly individuals. Home care was defined as a
      positive answer to the following question: "Do you have someone here in your home
      to take care of you?" The prevalence of home care was 49.5% (95% CI: 44.5; 54.5).
      Children and spouses were responsible for the majority of home care (40.7% and
      37%, respectively). Men, unaccompanied and physically inactive individuals, of
      advanced age, lower educational level, higher economic level, functionally
      disabled and who had been hospitalized in the last year characterized the profile
      of the dependent elderly individual. The high prevalence of home care can serve
      as input for health services for the elderly. Among all the characteristics,
      functional disability was the one most closely associated with home care.

PMID- 22634810
TI  - [Health care for elderly victims of violence in Rio de Janeiro].
AB  - The scope of this article is to chart, define and qualify the healthcare provided
      by the Brazilian Unified Health System (SUS) and outsourced services to elderly
      people in situations of violence in Rio de Janeiro, based on major policies aimed
      at this group. This is an exploratory study that triangulated quantitative and
      qualitative methods. The introduction and implementation of policies is
      differentiated between the units: they are more thoroughly implemented at the pre
      hospital and hospital level and less at rehabilitation level. The challenges
      involve the professional's ability to identify, attend and report cases of
      violence; to include the topic in care of the elderly; to give visibility to the
      specific requirements for elderly women; to instruct and orient families about
      care, creating strategies to redeem the bonds of affection; to monitor the
      changes that lead to functional disability and enhance the quality of life of the
      elderly.

PMID- 22634811
TI  - [Outsourcing in long-term care: a risk management approach].
AB  - This article seeks to investigate outsourcing decisions in supply chain
      management of healthcare organizations, namely the motives and constraints behind
      the decision, the selection criteria for activities to be outsourced to third
      parties, the type of possible agreements, and the impact of this decision on the
      organization per se. A case study of the start-up phase of a Long-term Care unit
      with an innovative approach and high levels of customization was conducted to
      understand the outsourcing process in a start-up context (not in the standard
      context of organizational change) and a risk evaluation matrix was created for
      outsourcing activities in order to define and implement a performance monitoring
      process. This study seeks to understand how to evaluate and assess the risks of
      an outsourcing strategy and proposes a monitoring model using risk management
      tools. It was shown that the risk management approach can be a solution for
      monitoring outsourcing in the organizational start-up phase. Conclusions
      concerning dissatisfaction with the results of outsourcing strategies adopted are
      also presented.

PMID- 22634813
TI  - [People living with HIV/AIDS and their link with the antiretrovirals provided by
      the National Programme in Argentina].
AB  - In accordance with the National AIDS Law, the Argentinian State is committed to
      supply antiretroviral medication (ARV) free of charge. Due to the complexity of
      the National ARV Program management process, and the fact that people with
      HIV/AIDS (PLHA) are the beneficiaries of the Program, it is considered relevant
      to ascertain their opinion. The aim of this work is to examine the supply of ARV
      by the National HIV/AIDS Program, from the perspective of PLHA, in a public
      hospital of the city of Rosario, in relation to: 1) value of the Program and the
      information received from it; 2) waiting times; 3) availability of ARV to
      continue the treatment. It is a qualitative study with interviews during January
      and February 2007 consisting of structured questions and patient criteria
      selection, in the presence of a psychologist. 15 PLHA were interviewed and gave
      their considered opinion about the Program and its background. They acknowledge
      difficulties in the continuity of ARV treatment and the consequences with respect
      to death and quality of life. The Program shows the coexistence between
      characteristics of a policy guaranteed by the state and others from programs that
      respond to emergencies. It shows the need to rethink the Program as a genuine
      health policy, considering ARV as essential medicine.

PMID- 22634812
TI  - [The role of the psychologist in hospitals and maternity wards in the state of
      Sergipe].
AB  - This article seeks to reflect on the professional activity of the psychologist in
      the hospital context by examining the role of psychologists working in hospitals
      and maternity wards in the State of Sergipe. It seeks to identify the specific
      role of these professionals in hospitals and maternity wards, as well as their
      motivating forces and the difficulties encountered. This work is part of a
      broader project that sought to study not only the activity per se, but also
      training aspects of these professionals. The sample was analyzed using a
      qualitative and quantitative approach for thematic analysis. Results revealed
      that the characterization of the role of psychologists has a focus on
      psychotherapeutic work with patients before and after surgery, as well as the
      caregivers and family members of critically ill patients in the following units:
      ICU, ICC, oncology, dialysis and surgical wards, offering support, especially at
      the pre- and post-surgery phase.

PMID- 22634814
TI  - [Poverty and social policy: the implementation of complementary programs for the
      Bolsa Familia Program].
AB  - The Bolsa Familia Program involves the transfer of income and the implementation
      of complementary programs to foster human capital development and empower the
      beneficiaries. To analyze the implementation of complementary programs in
      Manguinhos, Rio de Janeiro, a review of documents and secondary data was
      conducted, focus groups of beneficiaries studied and semi-structured interviews
      were staged with governmental, nongovernmental stakeholders and beneficiaries.
      The design, coverage and evaluation of the complementary programs have been weak,
      and beneficiaries were even unaware of vocational training courses. The program
      administrators acknowledged the failings and the fact that the courses offered by
      Proximo Passo are not adapted to local demand, even though they were conceived as
      a vocational training strategy aimed at creating construction jobs in the Growth
      Acceleration Program and the tourist industry in the city. Considering that the
      social inclusion perspective is linked to access to public policies, the supply
      and follow-up of these activities by government agencies and civil society
      organizations are essential for the effectiveness of the fight against poverty
      and hunger, aimed at contributing to the so-called "exit routes" from the Bolsa
      Familia Program.

PMID- 22634815
TI  - [Support groups for prostate cancer patients: integrative literature review].
AB  - This article is an integrative literature review to analyze the contribution of
      national and international studies examining the use of psychological support
      groups as a care strategy for patients diagnosed with prostate cancer. The
      electronic databases consulted were: LILACS, MedLine and PsycINFO, over a period
      of 20 years (1989-2009) with pre-defined criteria for inclusion. Eleven studies
      were selected, and based on their contributions some considerations are presented
      regarding the factors that favor male participation in the support groups and the
      potential benefits of such participation; as well as their main concerns and the
      influence of gender identity in the process of coping with illness. Furthermore,
      studies suggest some models of group intervention, along with orientation for the
      coordinators which emphasize the importance of these groups as an effective
      strategy to aid in the process of coping of prostate cancer patients.

PMID- 22634816
TI  - [Beyond bars and punishments: a systematic review of prison health].
AB  - A systematic review of scientific production on Prison Health was conducted,
      seeking to verify how the subject matter has been dealt with, establishing which
      is the most exploited focus and identifying possible gaps. The search was carried
      out in the Virtual Health Library. 1160 articles were located: 1104 on MEDLINE,
      19 on LILACS and 37 on SciELO, published from 1993 to 2010. As MEDLINE and LILACS
      do not show the entire articles, the places, dates and languages of the texts
      were charted. In-depth analysis was restricted to works which were shown in their
      entirety and free of charge hosted on SciELO. It revealed that scientific
      production is present all over the world with a predominantly quantitative
      approach. It focuses on identifying the socio-demographic profile and health
      conditions of prisoners, the incidence of tuberculosis, Human Immunodeficiency
      and Hepatitis C virus infections. There is a predominance of studies carried out
      with male prisoners, in comparison with the female sex. It is clear that prisoner
      health is a public health problem on the rise, which demands research that can
      orient health policies and strategies.

PMID- 22634817
TI  - [Knowledge derived from studies on crack: an incursion into Brazilian
      dissertations and theses].
AB  - This is a systematic review based on the integrative review method, which sought
      to analyze the characteristics of knowledge produced by studies on crack, in
      Brazilian Master's and Doctoral courses. The investigation comprised 33 studies
      (18 dissertations and 15 theses). Among them, 51.5% were from the Health Science
      area with emphasis on the Postgraduate Program in Psychiatry (and Medical
      Psychology), which provided five dissertations/theses. Most of the knowledge on
      the epidemic (51.5%) are from the Universidade Federal de Sao Paulo and
      Universidade de Sao Paulo, with the largest number of studies (81.8%)
      concentrated in the southeast. The themes most analyzed were: organic
      alterations, drug trafficking and crack use, HIV/Aids, types and strategies of
      treatment. The results showed that Brazilian stricto sensu knowledge about crack
      is still incipient, sketchy and ineffectual, albeit promising due to demands and
      implications that this epidemic imposes upon society.

PMID- 22634818
TI  - [Oral health conditions of the elderly at the Lar Samaritano long-term-care
      facility in Sao Goncalo-RJ].
AB  - With the increase in life expectancy in Brazil, there are increasing numbers of
      elderly. There is a marked increase in demand for Long-Term-Care Facilities for
      the elderly in Brazil, but there is little epidemiological data on oral health in
      such institutions. The objective is to evaluate the oral health of elderly
      residents in a Long-Term-Care Facility in Sao Goncalo city, Rio de Janeiro,
      examining dental conditions, the use of and need for prostheses and dental
      treatment. Quantitative research was conducted with functionally dependent and/or
      independent male and female subjects over 59 years of age, involving data
      gathering, consulting records, interviews and clinical examinations. DMFT 30.37,
      predominantly missing teeth and the female population with fewer decayed teeth.
      Only 2 had excellent hygiene, 25 were good, 17 satisfactory and 14 bad. Tooth
      mobility was found in 6 elderly though 52 had no mobility, while 32 wore dentures
      and 26 did not, with women using them more frequently. 49 lacked treatment,
      mainly women as they were greater in number. The conclusion reached is that Long
      Term-Care Facilities need inspection by public and dental authorities, with
      priority given to dental professionals, in addition to fostering academic
      activities for undergraduate and postgraduate students.

PMID- 22634819
TI  - [Urban work profile among adolescents aged 14-15 years: a population-based study
      in Southern Brazil].
AB  - The scope of this article was to describe the urban work patterns among 14 to 15
      year-old youths from Southern Brazil. Child labor was characterized as any
      activity that resulted in retribution in the form of goods, services or money.
      The analyses were stratified by sex and economic level. Of the 4325 adolescents
      interviewed, the proportion of labor in the last year was 22.2%, namely 27.7% for
      the male sex, and 17% for the female sex. This proportion was also higher among
      the poorer strata of the population (30.0%) than the more affluent (14.3%). The
      majority of adolescents worked away from home and approximately half of them
      began working before 14 years of age, and around 80.0% reported that they worked
      by choice. Only 1.0% had a labor contract or work booklet, 30.0% worked more than
      six hours per day, and the average income was less than US$85/month. Domestic
      work predominated among the poorest teenagers. There is a need for greater
      surveillance of child labor and of interventions seeking to enforce prevailing
      legislation.

PMID- 22634820
TI  - [The meaning that health professionals attribute to promotion of the health of
      adolescents].
AB  - This article analyzes the meanings attributed to practices that promote
      adolescent health by 47 professionals from the Family Health Program in Fortaleza
      in the State of Ceara. It is a qualitative study in which semi-structured
      interviews enabled the production of data, subsequently organized according to
      content analysis, resulting in the following core themes: promoting health
      associated with injury prevention; limitation of health promotion to the school
      environment; the lack of health promotion for adolescents in the healthcare
      service; and partnerships as a viable way of promoting health for adolescents.
      The health promotion actions were developed in a timely manner and mostly in the
      pre-natal, family planning, and cancer prevention programs. The health
      professionals found the school environment to be an important and viable place
      for a partnership for health promotion actions for adolescents. There was
      evidence, albeit incipient, of the health professionals' desire to reorient this
      practice in the healthcare service.

PMID- 22634821
TI  - Perceptions of dental students regarding dentistry, the job market and the public
      healthcare system.
AB  - The scope was to analyze the perceptions of dentistry students at the State
      University of Montes Claros, Brazil, regarding dentistry, the job market and the
      public healthcare system. For this, a triangulation method was employed, using a
      self-administered questionnaire and interviews. The quantitative data were
      submitted to univariate and multivariate analysis, using Poisson regression,
      where p<0.05. Content analysis was used for the qualitative data. The majority
      reported expecting to obtain work in the public healthcare system, stated that
      the dentistry course prepares students for this market as the curriculum
      integrates both teaching and service, reported being in favor of greater
      experience in the public healthcare system and said they would not take classes
      in Public Health if they were optional. Contact with the social context through
      teaching/service integration in the advanced semesters of the dentistry course
      appears to contribute to the development of new professional skills for working
      in the public sector. However, the students' perceptions revealed contradictions,
      considering the low value they attributed to the classes on Public Health and
      their perception of the public system as a residual job option.

PMID- 22634822
TI  - [Analysis of motor performance associated with the nutritional status of the
      elderly enrolled in the Family Health Program in the municipality of Vitoria de
      Santo Antao in the State of Pernambuco].
AB  - The scope of this paper was to investigate the relationship between the
      nutritional status and the motor skills of the elderly registered in the Family
      Health Program in the urban area of Vitoria de Santo Antao in the State of
      Pernambuco, by means of a transversal epistemological descriptive-analytical
      field study. The participants of this survey were 235 elders, both male and
      female of 60-years-old and over registered in the family health program in the
      urban area of the city. The nutritional status was evaluated by the body mass
      index and the circumference of the calf. Four motor tests were used to evaluate
      motor performance: Time Up&Go, Tinetti's Index, Functional Reach and Unipodal
      Support. The associations were checked using Spearman's correlation. The
      association of the nutritional status with the motor tests was statistically
      significant among males* or females**: (Time Up&Go rho = 0.290* / 350**;
      Functional Reach rho = 0.232* / 352**; Tinetti's Index rho = 243* / 363** and
      Unipodal Support rho = 221* / 475**. The evaluation of the results revealed an
      association between nutritional status and functional capacity of the elders no
      matter what gender; with obesity being a limiting nutritional condition to
      adequate performance in the tests.

PMID- 22634823
TI  - [The role of the community health agent in control of the in-house stock of
      medication in communities served by the family health strategy].
AB  - The scope of this study was to investigate the in-house stock of medication in
      communities served by the Family Health Strategy (FHS) in a city located in the
      south of Brazil. A sample of 10% of households in five FHS areas was studied.
      Data were collected by Community Healthcare Workers using the adapted Fernandes
      questionnaire (2000). The mean age of the interviewees was 42 years and of the
      residents was 16 years, 51% of which were female. Low income (1 to 3 minimum
      wages) was observed (69.1%), and low education levels (0 to 4 years of study)
      (42%). Of the households visited 98.7% had at least one medication in stock. In
      533 of the storage places located, 43.5% of such places were exposed to heat,
      39.6% were exposed to humidity and 16.51% to light. Of the 2,717 medicines found,
      6.9% were past the validity date, 35.3% were not in the secondary wrapping and
      67.9% were without the patient information leaflet. Analgesics were the most
      common medications in in-house stock (21%). This study revealed the need for a
      multi-professional team to promote health and the rationalization of in-house
      stock since the Community Healthcare Worker is an indispensable professional to
      promote the rational use of medication.

PMID- 22634824
TI  - [Reliability of the Nottingham Health Profile after suffering a stroke].
AB  - This article seeks to evaluate the reliability, internal consistency and accuracy
      of the Nottingham Health Profile (NHP), namely a quality of life (QL) instrument
      for individuals after suffering a stroke. This cross-sectional study was carried
      out in the communities of Recife in the State of Pernambuco. The sample was
      composed of 53 individuals at the chronic stroke phase. After checking the
      cognitive state, the NHP was applied. Descriptive statistics were employed for
      characterization of the sample; Cronbach's alpha (alpha) coefficients were used
      for evaluation of internal consistency, and intra-class correlation coefficients
      (ICC) were used for investigation of reliability, as well as consistency of the
      Bland and Altman plotting tests with 5% level of significance. Their perceptions
      of their own health were 83.3% positive for the majority of NHP criteria (average
      scores > 50 points), except for the "physical ability" criterion where scores
      ranged between 41.5 and 50 points. The NHP had good internal consistency with
      alpha values between 0.81 to 0.87; excellent reliability indices for the "pain"
      and "physical ability" criteria (ICC > 0.90); and 95% consistency. Besides being
      simple and easily applied, NHP had adequate clinimetric properties for the
      assessment of individuals after a chronic stroke.

PMID- 22634825
TI  - [Rational use of antibiotics: an experiment for the health education of
      schoolchildren].
AB  - The promotion of the rational use of antibiotics can be conducted to ensure that
      health professionals and users become aware of its importance through educational
      activities. The scope of this paper was to report on the experiment of developing
      a tool for health education for primary school children on the rational use of
      antibiotics. The activities began by defining objectives, selecting the best
      strategy and planning activities with the guidance of teaching assistants in
      schools. After defining that the strategy to be adopted would be a comic strip,
      we worked together with the children on the steps of contextualization, sequence
      construction and its illustration. All the goals established for the story were
      achieved, since it represented aspects envisaged in the concept of rational use
      of medicines recommended by the World Health Organization. At the end, the story
      that best matched the intended purposes was selected to be turned into a comic
      book. The experience showed a way to develop health education activities in
      interaction with the community, using recreational workshops. Beside this, it
      made it possible to identify the limitations and potential for using education
      action strategies on other topics with children of the same age group.

PMID- 22634826
TI  - [Oral health in the printed media: analysis of newspaper articles in the years
      2004-2009].
AB  - This study seeks to outline the main characteristics of the texts on oral health
      that appeared in the printed media in the State of Espirito Santo from 2004 to
      2009, in order to analyze and compare the issues, approaches and journalistic
      relevance related to the theme prioritized in A Tribuna and A Gazeta newspapers.
      Exploratory documentary research was conducted, based on quantitative content
      analysis of the material, which established that the issues included ranged from
      information about oral health policies, community service and prevention of oral
      health diseases, to the "aesthetic tendencies" of the smile. It also covered the
      dissemination of new technologies and dental specialties and there was a
      predominance of even-numbered pages, fewer first page texts and full-page
      coverage. This implies a moderate appreciation of these issues, different
      editorial projects, plus the difference in target audience that determined the
      journalistic standard and the predominance of specialized sources. Despite the
      oral health articles not revealing journalistic "scoops", they can be reworked
      using conscious journalistic techniques, in order to elicit the extraordinary
      from the ordinary, giving rise to texts of social relevance in both newspapers.

PMID- 22634827
TI  - [Primary healthcare and the construction of meanings of oral health: a social
      constructionist interpretation of discourses of the elderly].
AB  - Dentistry currently reveals itself to be open to new ideas about the construction
      of meanings for oral health. This openness leads to the social production of
      health revealing the contextualization of the social and historical aspects of
      the sundry knowledge in the development of oral health for different communities.
      With this research, we seek to build meanings for oral health with a group of
      elderly people. With this objective in mind, we propose an approximation between
      discourses on oral health mentioned by the elderly and the Social Constructionist
      discourse. We interviewed 14 elderly people enrolled in a Family Health Unit in
      Ribeirao Preto, State of Sao Paulo, in the first semester of 2010, and identified
      two interpretative repertoires through Discourse Analysis, which showed the
      relationship between 1 - Lack of information and dental assistance in childhood,
      and 2 - Primary Health Care building the meaning of oral health. We concluded
      that Social Constructionism works epistemologically for the construction of
      meanings for oral health and that primary health is essential for appreciation
      and health care that enables the construction of meanings in oral health by the
      elderly that create conditions for self-care and healthy attitudes.

PMID- 22634828
TI  - [Dental pain as the motive for absenteeism in a sample of workers].
AB  - The aim of this study was to analyze the prevalence of dental pain, absenteeism
      induced by dental pain, and the association with socio-demographic
      characteristics. The research had a cross-sectional design using a random sample
      of 170 municipal employees from the City of Venda Nova do Imigrante, Espirito
      Santo state, Brazil, selected from a universe of 545 individuals. Data was
      collected using a 27-item questionnaire applied by a municipal worker. The
      comparison of dental pain and prevalence of absenteeism with socio-demographic
      and functional characteristics was verified using Fisher's Exact test. The
      research project was approved by an Ethics Research Committee. The prevalence of
      dental pain among the employees was 43% and half of these felt dental pains at
      work. Absenteeism related to dental pain was 23.4%. Workers with lower
      instruction level were twice as likely to have dental pain (OR = 2,144, IC95% =
      1,141; 4,030). Male subjects (OR = 5,714, IC95% = 1,773; 18,416), less years of
      education (OR = 4,875, IC95% = 1,405; 16,909) and less family income (OR = 3,613,
      IC95% = 0,931; 14,021) were related with higher absenteeism caused by dental
      pain. High dental pain frequency revealed in this study indicates that health
      promotion policies are needed to improve the quality of life of workers.

PMID- 22634829
TI  - [Perceptions of hypertensive people on risk factors for the disease].
AB  - This paper sought to verify the perceptions of hypertensive people in relation to
      the risk factors and their experience with high blood pressure in a Reference
      Center for Cardiovascular Diseases in the city of Salvador. Interviews were
      staged with 33 hypertensive people. This is a descriptive study, of a qualitative
      nature, supported by the discourse analysis proposed by Foucault. It was observed
      that risk factors were confused with hypertension complications. Nevertheless,
      when the approach changed from "risk factors" to "factors that can increase blood
      pressure," it was seen that the answers were more coherent with the risk factors
      classified by the VI Brazilian Policies on Hypertension. Furthermore, it was also
      observed through the discourses that the perception of increase in blood pressure
      is directly related to experiences. Therefore, it is necessary that the guidance
      be transmitted as clearly as possible in order for the understanding to become an
      important facilitator for controlling the illness. This paper enabled the
      perception of the risk factors in the viewpoint of these people in such a manner
      as to supply clues for the interdisciplinary health team to promote healthcare
      based on the experiences and the socio-economic and cultural context in which
      these people are inserted.

PMID- 22634831
TI  - Implementation of a novel communication tool and its effect on patient
      comprehension of care and satisfaction.
AB  - BACKGROUND: Emergency department (ED) communication has been demonstrated as
      requiring improvement and ED patients have repeatedly demonstrated poor
      comprehension of the care they receive. Through patient focus groups, the authors
      developed a novel tool designed to improve communication and patient
      comprehension. STUDY DESIGN: This is a prospective, randomised controlled
      clinical trial to test the efficacy of a novel, patient-centred communication
      tool. Patients in a small community hospital ED were randomised to receive the
      instrument, which was utilised by the entire ED care team and served as a
      checklist or guide to the patients' ED stay. At the end of the ED stay, patients
      completed a survey of their comprehension of the care and a communication
      assessment tool-team survey (a validated instrument to assess satisfaction with
      communication). Three blinded chart reviewers scored patients' comprehension of
      their ED care as concordant, partially concordant or discordant with charted
      care. The authors tested whether there was a difference in satisfaction using a
      two-sample t test and a difference in comprehension using ordinal logistic
      regression analysis. RESULTS: 146 patients were enrolled in the study with 72
      randomised to receive the communication instrument. There was no significant
      difference between groups in comprehension (OR=0.65, 95% CI 0.34 to 1.23, p=0.18)
      or communication assessment tool-team scores (difference=0.2, 95% CI: -3.4 to
      3.8, p=0.91). CONCLUSIONS: Using their novel communication tool, the authors were
      not able to show a statistically significant improvement in either comprehension
      or satisfaction, though a tendency towards improved comprehension was seen.

PMID- 22634832
TI  - Analysis of emergency physicians' Twitter accounts.
AB  - BACKGROUND: Twitter is one of the fastest growing social media networks for
      communication between users via short messages. Technology proficient physicians
      have demonstrated enthusiasm in adopting social media for their work. OBJECTIVE:
      To identify and create the largest directory of emergency physicians on Twitter,
      analyse their user accounts and reveal details behind their connections. METHODS:
      Several web search tools were used to identify emergency physicians on Twitter
      with biographies completely or partially written in English. NodeXL software was
      used to calculate emergency physicians' Twitter network metrics and create
      visualisation graphs. RESULTS: The authors found 672 Twitter accounts of self
      identified emergency physicians. Protected accounts were excluded from the study,
      leaving 632 for further analysis. Most emergency physicians were located in USA
      (55.4%), had created their accounts in 2009 (43.4%), used their full personal
      name (77.5%) and provided a custom profile picture (92.2%). Based on at least one
      published tweet in the last 15 days, there were 345 (54.6%) active users on 31
      December 2011. Active users mostly used mobile devices based on the Apple
      operating system to publish tweets (69.2%). Visualisation of emergency
      physicians' Twitter network revealed many users with no connections with their
      colleagues, and a small group of most influential users who were highly
      interconnected. CONCLUSIONS: Only a small proportion of registered emergency
      physicians use Twitter. Among them exists a smaller inner network of emergency
      physicians with strong social bonds that is using Twitter's full potentials for
      professional development.

PMID- 22634834
TI  - Synthesis of chalcones with anticancer activities.
AB  - Several chalcones were synthesized and their in vitro cytotoxicity against
      various human cell lines, including human breast adenocarcinoma cell line MCF-7,
      human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3,
      human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver
      cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic
      agents, four of them with minimal IC50 values were chosen and studied in detail
      with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting
      apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and
      caspase-3/7, -8, and -9 activities (p < 0.05). The ROS level showed 1.3-fold
      increase (p < 0.05) at the low concentrations used and thus it was concluded that
      the compounds increased the ROS level eventually leading to apoptosis in MCF-7
      cells through intrinsic as well as extrinsic pathways.

PMID- 22634835
TI  - Embryonic stem cell markers.
AB  - Embryonic stem cell (ESC) markers are molecules specifically expressed in ES
      cells. Understanding of the functions of these markers is critical for
      characterization and elucidation for the mechanism of ESC pluripotent maintenance
      and self-renewal, therefore helping to accelerate the clinical application of ES
      cells. Unfortunately, different cell types can share single or sometimes multiple
      markers; thus the main obstacle in the clinical application of ESC is to purify
      ES cells from other types of cells, especially tumor cells. Currently, the marker
      based flow cytometry (FCM) technique and magnetic cell sorting (MACS) are the
      most effective cell isolating methods, and a detailed maker list will help to
      initially identify, as well as isolate ESCs using these methods. In the current
      review, we discuss a wide range of cell surface and generic molecular markers
      that are indicative of the undifferentiated ESCs. Other types of molecules, such
      as lectins and peptides, which bind to ESC via affinity and specificity, are also
      summarized. In addition, we review several markers that overlap with tumor stem
      cells (TSCs), which suggest that uncertainty still exists regarding the benefits
      of using these markers alone or in various combinations when identifying and
      isolating cells.

PMID- 22634836
TI  - Antiatherogenic properties of acetone extract of Alpinia zerumbet seeds.
AB  - Oxidation of low-density lipoprotein (LDL) is the principal risk factor for the
      development of atherosclerosis. In this study, we used several methods to
      investigate the ability of the acetone extract from rhizomes, stems, leaves,
      flowers, pericarps and seeds of Alpinia zerumbet to inhibit atherosclerosis in
      vitro. The seed extract had the strongest activity against tyrosinase, pancreatic
      lipase (PL), 15-lipoxygenase (15-LO) and LDL oxidation activities (IC50 = 2.30 +/
      0.02, 5.00 +/- 0.07, 1.29 +/- 0.07 and 15.40 +/- 0.86 MUg/mL, respectively),
      amongst all different parts. It also had similar effects to the positive
      controls. Most of the extracts showed partial agonistic properties towards
      estrogenic activity. Cholest-4-ene-3,6-dione, a steroid present only in the seed
      extract seems to be the compound responsible for these activities. The results
      showed that cholest-4-ene-3,6-dione had similar ability to curcumin and quercetin
      against PL and LDL oxidation (IC50 = 19.50 +/- 1.17 and 16.12 +/- 1.43 MUg/mL,
      respectively). Furthermore, cholest-4-ene-3,6-dione (IC50 = 34.21 +/- 1.31
      MUg/mL) had higher inhibition against 15-LO than quercetin (IC50 = 54.79 +/- 1.12
      MUg/mL).

PMID- 22634837
TI  - Synthesis and antiangiogenic activity of novel gambogic acid derivatives.
AB  - Gambogic acid (GA) is in a phase II clinical trial as an antitumor and
      antiangiogenesis agent. In this study, 36 GA derivatives were synthesized and
      screened in a zebrafish model to evaluate their antiangiogenic activity and
      toxicity. Derivatives 4, 32, 35, 36 effectively suppressed the formation of newly
      grown blood vessels and showed lower toxicities than GA as evaluated by zebrafish
      heart rates and mortalities. They also exhibited more potent migration and HUVEC
      tube formation inhibiting activities than GA. Among them, 36 was the most potent
      one, suggesting that it may serve as a potential new antiangiogenesis candidate
      with low toxicity. Additionally, 36 showed comparable antiproliferative activity
      to HUVECs and five tumor cell lines but low cytotoxicity to LO2 cells.

PMID- 22634838
TI  - alpha-Glucosidase inhibitory constituents from Acanthopanax senticosus harm
      leaves.
AB  - A new triterpene glycoside, 3-O-[(alpha-L-rhamnopyranosyl)(1->2)]-[beta-D
      glucuronopyranosyl-6-O-methyl ester]-olean-12-ene-28-olic acid (1) and a new
      indole alkaloid, 5-methoxy-2-oxoindolin-3-acetic acid methyl ester (5) were
      isolated from the leaves of Acanthopanax senticosus Harms along with six known
      compounds. The structures of the new compounds were determined by means of 2D-NMR
      experiments and chemical methods. All the isolated compounds were evaluated for
      their glycosidase inhibition activities and compound 6 showed significant alpha
      glucosidase inhibition activity.

PMID- 22634839
TI  - Scutellaria baicalensis alleviates cantharidin-induced rat hemorrhagic cystitis
      through inhibition of cyclooxygenase-2 overexpression.
AB  - Cantharidin, an active component in mylabris, is used in traditional Chinese
      medicine (TCM) to treat scabies and hepatoma, but accompanied by hemorrhagic
      cystitis. Evidence shows that cantharidin induces human bladder carcinoma cell
      death through COX-2 overexpression in vitro. In TCM, Scutellaria baicalensis is
      usually used to cure mylabris-induced hematuria. This work was undertaken to
      determine the mechanisms of cantharidin-induced rat hemorrhagic cystitis and
      explore the uroprotective effect of S. baicalensis. In vitro results showed
      cantharidin could induce cytotoxicity through prostaglandin (PG)E2 overproduction
      of T24 cells. Boiling-water extract of S. baicalensis (SB-WE) could significantly
      inhibit PGE2 production and COX-2 expression in lipo-polysaccharide-induced RAW
      264.7 cells, indicating obvious anti-inflammatory abilities. In vivo results
      indicated that cantharidin caused rat hemorrhagic cystitis with hematuria via c
      Fos and COX-2 overexpression. SB-WE was given orally to cantharidin-treated rats,
      whereby hematuria level, elevated PGE2 and COX-2 protein overexpression were
      significantly and dose-dependently inhibited by SB-WE. The anti-inflammatory
      components of SB-WE are baicalin and wogonin, whose contents were 200.95 +/- 2.00
      and 31.93 +/- 0.26 MUg/mg, respectively. In conclusion, cantharidin induces rat
      cystitis through c-Fos and COX-2 over-expression and S. baicalensis can prevent
      the resulting hematuria because of its anti-inflammatory effects.

PMID- 22634840
TI  - Antiproliferative and molecular mechanism of eugenol-induced apoptosis in cancer
      cells.
AB  - Phenolic phytochemicals are a broad class of nutraceuticals found in plants which
      have been extensively researched by scientists for their health-promoting
      potential. One such a compound which has been comprehensively used is eugenol (4
      allyl-2-methoxyphenol), which is the active component of Syzigium aromaticum
      (cloves). Aromatic plants like nutmeg, basil, cinnamon and bay leaves also
      contain eugenol. Eugenol has a wide range of applications like perfumeries,
      flavorings, essential oils and in medicine as a local antiseptic and anesthetic.
      Increasing volumes of literature showed eugenol possesses antioxidant,
      antimutagenic, antigenotoxic, anti-inflammatory and anticancer properties.
      Molecular mechanism of eugenol-induced apoptosis in melanoma, skin tumors,
      osteosarcoma, leukemia, gastric and mast cells has been well documented. This
      review article will highlight the antiproliferative activity and molecular
      mechanism of the eugenol induced apoptosis against the cancer cells and animal
      models.

PMID- 22634841
TI  - Biological activities of alpha-pinene and beta-pinene enantiomers.
AB  - The antimicrobial activities of the isomers and enantiomers of pinene were
      evaluated against bacterial and fungal cells. The agar diffusion test showed that
      only the positive enantiomers of the alpha- and beta-isomers of pinene were
      active. The minimal inhibitory concentration (MIC) and minimal microbicidal
      concentration (MMC) of these monoterpenes were also determined, confirming that
      the positive enantiomers exhibited microbicidal activity against all fungi and
      bacteria tested with MICs ranging from 117 to 4,150 MUg/mL. However, no
      antimicrobial activity was detected with the negative enantiomers up to 20 mg/mL.
      Time-kill curves showed that (+)-alpha-pinene and (+)-beta-pinene were highly
      toxic to Candida albicans, killing 100% of inoculum within 60 min. By contrast,
      the bactericidal effect occurred after 6 h in methicillin-resistant
      Staphylococcus aureus (MRSA). In combination with commercial antimicrobials,
      ciprofloxacin plus (+)-alpha-pinene or (+)-beta-pinene presented synergistic
      activity against MRSA whereas an indifferent effect against all fungi was
      detected when amphotericin B was combined with the positive enantiomers of
      pinene. The potential of (+)-alpha-pinene and (+)-beta-pinene to inhibit
      phospholipase and esterase activities was also evaluated, and the best inhibition
      results were obtained with Cryptococcus neoformans. C. albicans biofilm formation
      was prevented with the MIC concentration of (+)-alpha-pinene and twice the MIC
      value of (+)-beta-pinene. Finally, the cytotoxicity of the positive enantiomers
      of pinene to murine macrophages was evaluated, and 250 MUg/mL of (+)-alpha-pinene
      and (+)-beta-pinene reduced the cell viability to 66.8% and 57.7%, respectively.

PMID- 22634843
TI  - Phenolics and flavonoids compounds, phenylanine ammonia lyase and antioxidant
      activity responses to elevated CO2 in Labisia pumila (Myrisinaceae).
AB  - A split plot 3 * 3 experiment was designed to examine the impact of three
      concentrations of CO2 (400, 800 and 1,200 MUmol.mol-1) on the phenolic and
      flavonoid compound profiles, phenylalanine ammonia lyase (PAL) and antioxidant
      activity in three varieties of Labisia pumila Benth. (var. alata, pumila and
      lanceolata) after 15 weeks of exposure. HPLC analysis revealed a strong influence
      of increased CO2 concentration on the modification of phenolic and flavonoid
      profiles, whose intensity depended on the interaction between CO2 levels and L.
      pumila varieties. Gallic acid and quercetin were the most abundant phenolics and
      flavonoids commonly present in all the varieties. With elevated CO2 (1,200
      MUmol.mol-1) exposure, gallic acid increased tremendously, especially in var.
      alata and pumila (101-111%), whilst a large quercetin increase was noted in var.
      lanceolata (260%), followed closely by alata (201%). Kaempferol, although
      detected under ambient CO2 conditions, was undetected in all varieties after
      exposure. Instead, caffeic acid was enhanced tremendously in var. alata
      (338~1,100%) and pumila (298~433%). Meanwhile, pyragallol and rutin were only
      seen in var. alata (810 MUg.g-1 DW) and pumila (25 MUg.g-1 DW), respectively,
      under ambient conditions; but the former compound went undetected in all
      varieties while rutin continued to increase by 262% after CO2 enrichment.
      Interestingly, naringenin that was present in all varieties under ambient
      conditions went undetected under enrichment, except for var. pumila where it was
      enhanced by 1,100%. PAL activity, DPPH and FRAP also increased with increasing
      CO2 levels implying the possible improvement of health-promoting quality of
      Malaysian L. pumila under high CO2 enrichment conditions.

PMID- 22634842
TI  - Synthesis and biological evaluation of novel N-methyl-picolinamide-4-thiol
      derivatives as potential antitumor agents.
AB  - A novel series of N-methylpicolinamide-4-thiol derivatives were synthesized and
      evaluated on human cancer cell lines. Among them, compound 6p displayed potent
      and broad-spectrum anti-proliferative activities in vitro on some human cancer
      cell lines, even better than sorafenib. The advanced kinase inhibitory assays
      showed that compound 6p could selectively inhibit Aurora-B kinase. The biological
      results were rationalized by the molecular docking study, which indicated the
      stable interactions of 6p with the Aurora-B kinase.

PMID- 22634844
TI  - Zinc phthalocyanine labelled polyethylene glycol: preparation, characterization,
      interaction with bovine serum albumin and near infrared fluorescence imaging in
      vivo.
AB  - Zinc phthalocyanine labelled polyethylene glycol was prepared to track and
      monitor the in vivo fate of polyethylene glycol. The chemical structures were
      characterized by nuclear magnetic resonance and infrared spectroscopy. Their
      light stability and fluorescence quantum yield were evaluated by UV-Visible and
      fluorescence spectroscopy methods. The interaction of zinc phthalocyanine
      labelled polyethylene glycol with bovine serum albumin was evaluated by
      fluorescence titration and isothermal titration calorimetry methods. Optical
      imaging in vivo, organ aggregation as well as distribution of fluorescence
      experiments for tracking polyethylene glycol were performed with zinc
      phthalocyanine labelled polyethylene glycol as fluorescent agent. Results show
      that zinc phthalocyanine labelled polyethylene glycol has good optical stability
      and high emission ability in the near infrared region. Imaging results
      demonstrate that zinc phthalocyanine labelled polyethylene glycol can track and
      monitor the in vivo process by near infrared fluorescence imaging, which implies
      its potential in biomaterials evaluation in vivo by a real-time noninvasive
      method.

PMID- 22634845
TI  - 4-Thiazolidinones in heterocyclic synthesis: synthesis of novel enaminones,
      azolopyrimidines and 2-arylimino-5-arylidene-4-thiazolidinones.
AB  - The 4-thiazolidinones 3a-d were used as a key intermediates for the synthesis of
      2-arylimino-5-arylidene-4-thiazolidinones derivatives 7a-p via nucleophilic
      addition reactions with the arylidene malononitrile. Moreover the 4
      thiazolidinones 3a and 3c condensed with the DMF-DMA to form the corresponding
      enamines 8 and 9 depending on the reaction conditions. Otherwise the 4
      thiazolidinone 3b reacts regioselectively with DMF-DMA to afford the enaminones
      10 and 11, respectively. The latter reacts with many heterocyclic amines
      affording polyfunctionally substituted fused pyrimidine derivatives 13-18. The
      enamine 8b was also reacted with the 3-amino-1,2,4-triazole to afford the acyclic
      product 19, which could not be further cyclized to the corresponding tricyclic
      system 20. Moreover the 4-thiazolidinone 3c reacted with the benzenediazonium
      chloride to afford the arylhydrazones 12. The X-ray single crystal technique was
      employed in this study for structure elucidation and Z/E potential isomerism
      configuration determination. The X-ray crystallographic analyses of eight
      products could be obtained, thus establishing with certainty the structures
      proposed in this work.

PMID- 22634846
TI  - Preparation of quinolinium salts differing in the length of the alkyl side chain.
AB  - Quaternary quinolinium salts differing in alkyl chain length are members of a
      widespread group of cationic surfactants. These compounds have numerous
      applications in various branches of industry and research. In this work, the
      preparation of quinoline-derived cationic surface active agents differing in the
      length of the side alkyl chains (from C8 to C20) is described. An HPLC method was
      successfully developed for distinction of all members of the series of prepared
      long-chain quinolinium derivatives. In conclusion, some possibilities of intended
      tests or usage have been summarized. In vitro testing using a microdilution broth
      method showed good activity of a substance with a C12 chain length against Gram
      positive cocci and Candida species.

PMID- 22634847
TI  - Chemistry of fullerene epoxides: synthesis, structure, and nucleophilic
      substitution-addition reactivity.
AB  - Fullerene epoxides, C60O(n), having epoxide groups directly attached to the
      fullerene cage, constitute an interesting class of fullerene derivatives. In
      particular, the chemical transformations of fullerene epoxides are expected to
      play an important role in the development of functionalized fullerenes. This is
      because such transformations can readily afford a variety of mono- or
      polyfunctionalized fullerene derivatives while conserving the epoxy ring
      arrangement on the fullerene surface, as seen in representative regioisomeric
      fullerene polyepoxides. The first part of this review addresses the synthesis and
      structural characterization of fullerene epoxides. The formation of fullerene
      epoxides through different oxidation reactions is then explored. Adequate
      characterization of the isolated fullerene epoxides was achieved by concerted use
      of NMR and LC-MS techniques. The second part of this review addresses the
      substitution of fullerene epoxides in the presence of a Lewis acid catalyst. Most
      major substitution products have been isolated as pure compounds and their
      structures established through spectroscopic methods. The correlation between the
      structure of the substitution product and the oxygenation pattern of the starting
      materials allows elucidation of the mechanistic features of this transformation.
      This approach promises to lead to rigorous regioselective production of various
      fullerene derivatives for a wide range of applications.

PMID- 22634848
TI  - Preoperative testing in noncardiac surgery patients:  a survey amongst European
      anaesthesiologists.
AB  - CONTEXT: Previous surveys of the current practice of preoperative assessment
      within different countries have shown that there is much variation between
      different hospitals. OBJECTIVE: The aim of the present study was to document the
      current clinical practice of preoperative testing for noncardiac surgery in
      Europe. We also wanted to assess the opinion of anaesthesiologists on eliminating
      routine preoperative testing. DESIGN: Cross-sectional study. SETTING:
      Anaesthesiologists from 17 different countries in Europe were surveyed between
      May and July 2009. PARTICIPANTS: Anaesthesiologists registered with a national
      anaesthesiology society represented in the European Society of Anaesthesiology.
      MAIN OUTCOME MEASURES: Indications for preoperative tests in different countries
      within Europe. RESULTS: We received 354 completed questionnaires from 17
      countries, all from different hospitals. In most countries, the anaesthesiologist
      has the final responsibility of performing preoperative evaluation (83%) and a
      preoperative assessment clinic is commonplace (95%). There is a remarkable
      variation in the way tests are ordered in different practices and also between
      different countries. About half of the anaesthesiologists indicated that they
      order preoperative tests in accordance with guidelines. Most respondents (86%)
      indicated that they would support moves towards a reduction in preoperative
      testing, but 44% cited patient safety as the main concern if routine testing was
      eliminated. CONCLUSION: Our survey shows a large variety in organisation and
      practice of preoperative evaluation throughout Europe. This practice is
      frequently not in accordance with guideline recommendations. Our survey confirms
      that there is a shift towards selective testing and also that the majority of
      respondents support a move towards reducing preoperative testing.

PMID- 22634849
TI  - Combining head-neck position and head-down tilt to prevent pulmonary aspiration
      of gastric contents during induction of anaesthesia:  a volunteer and manikin
      study.
AB  - CONTEXT: Although a life-threatening complication, pulmonary aspiration of
      gastric contents caused by vomiting or regurgitation during induction of
      anaesthesia cannot be prevented. It may be prevented if the mouth is placed more
      inferiorly than the larynx and tracheal bifurcation by the use of head-down tilt
      and head-neck positioning. OBJECTIVE: We aimed to determine the head-down tilt
      required to prevent aspiration in the neutral, simple extension, sniffing and
      full cervical spine extension (Sellick) positions and to investigate the
      relationship between pulmonary aspiration and the vertical height of the mouth,
      larynx and tracheal bifurcation. DESIGN: Observational study. SETTING: Operating
      theatre at Nippon Steel Yawata Memorial Hospital. PATIENTS: Manikins with
      coloured fluid in the oesophagus and 30 adult volunteers. INTERVENTIONS: Use of
      head-down tilt between 0 degrees  and 50 degrees  in 5 degrees  increments in
      four head-neck positions (neutral, simple extension, sniffing and Sellick). MAIN
      OUTCOME MEASURES: Aspiration of oesophageal contents (coloured fluid) from the
      oesophagus into the trachea and bronchi. Measurement of the mouth-arytenoid angle
      (manikin and volunteers) and the mouth-carina angle (manikin). RESULTS: The head
      down tilts required to protect both the trachea and bronchi from aspiration were
      45 degrees , 35 degrees  and 10 degrees  in the neutral, simple extension and
      Sellick positions, respectively, which coincided with the mouth-arytenoid angle
      in those positions. The maximum tilt used in this study was not adequate to
      prevent aspiration in the sniffing position. The head-down tilt required to level
      the mouth with the tracheal bifurcation (mouth-carina angle) protected the
      bronchi from aspiration but not the trachea. CONCLUSION: A head-down tilt equal
      to the mouth-arytenoid angle (levelling the mouth with the larynx) was necessary
      to completely prevent aspiration. This angle of tilt was within clinically
      relevant ranges only with the Sellick position.

PMID- 22634850
TI  - Are we not there yet? Who can keep the pandora box safe?

PMID- 22634851
TI  - Rational comparison of tracheal intubation with direct and indirect laryngoscopes
      in a simulated trapped manikin.

PMID- 22634852
TI  - Co-modulatory spectral changes in independent brain processes are correlated with
      task performance.
AB  - This study investigates the independent modulators that mediate the power spectra
      of electrophysiological processes, measured by electroencephalogram (EEG), in a
      sustained-attention experiment. EEG and behavioral data were collected during 1-2
      hour virtual-reality based driving experiments in which subjects were instructed
      to maintain their cruising position and compensate for randomly induced drift
      using the steering wheel. Independent component analysis (ICA) applied to 30
      channel EEG data separated the recorded EEG signals into a sum of maximally
      temporally independent components (ICs) for each of 30 subjects. Logarithmic
      spectra of resultant IC activities were then decomposed by principal component
      analysis, followed by ICA, to find spectrally fixed and temporally independent
      modulators (IM). Across subjects, the spectral ICA consistently found four
      performance-related independent modulators: delta, delta-theta, alpha, and beta
      modulators that multiplicatively affected the spectra of spatially distinct IC
      processes when the participants experienced waves of alternating alertness and
      drowsiness during long-hour simulated driving. The activation of the delta-theta
      modulator increased monotonically as subjects' task performances decreased.
      Furthermore, the time courses of the theta-beta modulator were highly correlated
      with concurrent changes in driving errors across subjects (r=0.77+/-0.13).

PMID- 22634853
TI  - The N170, not the P1, indexes the earliest time for categorical perception of
      faces, regardless of interstimulus variance.
AB  - A negative event-related potential (ERP) at occipito-temporal sites peaking
      around 150-170 ms after stimulus onset (N170) is typically larger for faces than
      other object categories. Most theories interpret this finding as due to face
      selective processing in occipito-temporal and temporal cortex. However, a
      controversial account recently attributed the N170 effect to differences in
      interstimulus variance (ISV) among the images typically used for face and object
      conditions and proposed that the earlier P1 instead indexes the categorical
      processes generally attributed to the N170. This ERP study aimed to test this
      account definitively by using conditions in which the same face and object were
      shown repeatedly, eliminating both physical and perceptual ISV. Fourier amplitude
      spectra of faces and objects were matched to equate basic low-level visual
      properties that may affect early ERPs such as the P1. Results demonstrate that i)
      face selectivity of the N170 is largely preserved across many object categories
      after abolishing ISV, and ii) stimulus category does not modulate the P1. This
      conclusively refutes the ISV account while strongly supporting category as a
      critical factor driving N170 face selectivity.

PMID- 22634854
TI  - Common substrate for mental arithmetic and finger representation in the parietal
      cortex.
AB  - The history of mathematics provides several examples of the use of fingers to
      count or calculate. These observations converge with developmental data showing
      that fingers play a critical role in the acquisition of arithmetic knowledge.
      Further studies evidenced specific interference of finger movements with
      arithmetic problem solving in adults, raising the question of whether or not
      finger and number manipulations rely on common brain areas. In the present study,
      functional magnetic resonance imaging (fMRI) was used to investigate the possible
      overlap between the brain areas involved in mental arithmetic and those involved
      in finger discrimination. Solving subtraction and multiplication problems was
      found to increase cerebral activation bilaterally in the horizontal part of the
      intraparietal sulcus (hIPS) and in the posterior part of the superior parietal
      lobule (PSPL). Finger discrimination was associated with increased activity in a
      bilateral occipito-parieto-precentral network extending from the extrastriate
      body area to the primary somatosensory and motor cortices. A conjunction analysis
      showed common areas for mental arithmetic and finger representation in the hIPS
      and PSPL bilaterally. Voxelwise correlations further showed that finger
      discrimination and mental arithmetic induced a similar pattern of activity within
      the parietal areas only. Pattern similarity was more important for the left than
      for the right hIPS and for subtraction than for multiplication. These findings
      provide the first evidence that the brain circuits involved in finger
      representation also underlie arithmetic operations in adults.

PMID- 22634855
TI  - Modulations of functional connectivity in the healthy and schizophrenia groups
      during task and rest.
AB  - Connectivity analysis using functional magnetic resonance imaging (fMRI) data is
      an important area, useful for the identification of biomarkers for various mental
      disorders, including schizophrenia. Most studies to date have focused on resting
      data, while the study of functional connectivity during task and the differences
      between task and rest are of great interest as well. In this work, we examine the
      graph-theoretical properties of the connectivity maps constructed using spatial
      components derived from independent component analysis (ICA) for healthy controls
      and patients with schizophrenia during an auditory oddball task (AOD) and at
      extended rest. We estimate functional connectivity using the higher-order
      statistical dependence, i.e., mutual information among the ICA spatial
      components, instead of the typically used temporal correlation. We also define
      three novel topological metrics based on the modules of brain networks obtained
      using a clustering approach. Our experimental results show that although the
      schizophrenia patients preserve the small-world property, they present a
      significantly lower small-worldness during both AOD task and rest when compared
      to the healthy controls, indicating a consistent tendency towards a more random
      organization of brain networks. In addition, the task-induced modulations to
      topological measures of several components involving motor, cerebellum and
      parietal regions are altered in patients relative to controls, providing further
      evidence for the aberrant connectivity in schizophrenia.

PMID- 22634856
TI  - Amygdala-prefrontal coupling underlies individual differences in emotion
      regulation.
AB  - Despite growing evidence on the neural bases of emotion regulation, little is
      known about the mechanisms underlying individual differences in cognitive
      regulation of negative emotion, and few studies have used objective measures to
      quantify regulatory success. Using a trait-like psychophysiological measure of
      emotion regulation, corrugator electromyography, we obtained an objective index
      of the ability to cognitively reappraise negative emotion in 56 healthy men
      (Session 1), who returned 1.3 years later to perform the same regulation task
      using fMRI (Session 2). Results indicated that the corrugator measure of
      regulatory skill predicted amygdala-prefrontal functional connectivity.
      Individuals with greater ability to down-regulate negative emotion as indexed by
      corrugator at Session 1 showed not only greater amygdala attenuation but also
      greater inverse connectivity between the amygdala and several sectors of the
      prefrontal cortex while down-regulating negative emotion at Session 2. Our
      results demonstrate that individual differences in emotion regulation are stable
      over time and underscore the important role of amygdala-prefrontal coupling for
      successful regulation of negative emotion.

PMID- 22634857
TI  - Dynamic Causal Modelling of epileptic seizure propagation pathways: a combined
      EEG-fMRI study.
AB  - Simultaneous EEG-fMRI offers the possibility of non-invasively studying the
      spatiotemporal dynamics of epileptic activity propagation from the focus towards
      an extended brain network, through the identification of the haemodynamic
      correlates of ictal electrical discharges. In epilepsy associated with
      hypothalamic hamartomas (HH), seizures are known to originate in the HH but
      different propagation pathways have been proposed. Here, Dynamic Causal Modelling
      (DCM) was employed to estimate the seizure propagation pathway from fMRI data
      recorded in a HH patient, by testing a set of clinically plausible network
      connectivity models of discharge propagation. The model consistent with early
      propagation from the HH to the temporal-occipital lobe followed by the frontal
      lobe was selected as the most likely model to explain the data. Our results
      demonstrate the applicability of DCM to investigate patient-specific effective
      connectivity in epileptic networks identified with EEG-fMRI. In this way, it is
      possible to study the propagation pathway of seizure activity, which has
      potentially great impact in the decision of the surgical approach for epilepsy
      treatment.

PMID- 22634858
TI  - Go with the flow: use of a directed phase lag index (dPLI) to characterize
      patterns of phase relations in a large-scale model of brain dynamics.
AB  - We introduce a directed phase lag index to investigate the spatial and temporal
      pattern of phase relations of oscillatory activity in a model of macroscopic
      structural and functional brain networks. Direction of information flow was
      determined with the directed phase lag index (dPLI) defined as the probability
      that the instantaneous phase of X was smaller than the phase of Y (modulo pi). X
      was said to phase-lead Y if 0.5<dPLI(XY)<=1. The dPLI was used to characterize
      the phase relations between simulated EEG time series. The model consisted of 78
      brain regions, coupled according to DTI findings in human subjects (Gong et al.,
      2009). Activity of each brain region was simulated with a neural mass model.
      Phase patterns were investigated as a function of coupling strength without
      stimulation, and with stimulation of the primary visual areas. At rest a clear
      spatial pattern of phase relations emerged with regions belonging to the anterior
      part of the default mode network leading in phase and regions belonging to the
      posterior part of the default mode network and surrounding visual areas lagging
      in phase. Patterns of phase leading and lagging displayed characteristic patterns
      with time scales from a few hundred milliseconds to 1-2 s. Stimulation of the
      primary visual areas induced a reversal of the global phase pattern with the
      visual and basal temporal areas leading and the anterior and superior frontal
      areas lagging in phase. This study shows that the directed phase lag index (dPLI)
      is an effective measure to characterize spatial temporal patterns of phase
      relations at rest and during stimulation. Coupling strength and node degree were
      found to be critical determinants of the direction of information flow. At a
      timescale of milliseconds to seconds the phase dynamics revealed spontaneous
      structure that might correspond to previously described "microstates".
      Stimulation of two visual areas reversed the global pattern of phase relations.

PMID- 22634860
TI  - Linking ordering in Broca's area to storage in left temporo-parietal regions: the
      case of sentence processing.
AB  - In sentence processing, storage and ordering of the verb and its arguments
      (subject and object) are core tasks. Their cortical representation is a matter of
      ongoing debate, and it is unclear whether prefrontal activations in neuroimaging
      studies on sentence processing reflect the storage of arguments or their
      ordering. Moreover, it is unclear how storage during sentence processing relates
      to the neuroanatomy of storage outside the sentence processing domain. To tackle
      these questions, we crossed the factor "ordering" (subject-first vs. object-first
      German sentences) with the factor "storage" (one vs. four phrases intervene
      between the critical argument and the verb) in an auditory fMRI study. Ordering
      focally activated the left pars opercularis in Broca's area, while storage
      activated deep left temporo-parietal (TP) regions. Notably, left TP activation
      correlated with listener's digit span, while Broca's area activation did not.
      Furthermore, fractional anisotropy of listeners' left arcuate fasciculus/superior
      longitudinal fasciculus (AF/SLF) is shown to covary with the functional effect of
      increased storage demands at sites along the tract. Functionally, the results
      suggest that storage during sentence processing relies on TP regions, likely
      shared between sentence processing and other working memory-related tasks, while
      Broca's area appears as a distinct neural correlate of ordering. We conclude that
      the abstract notion of sentence processing can be captured by the interplay of
      concrete cognitive concepts such as ordering and storage.

PMID- 22634859
TI  - LABEL: pediatric brain extraction using learning-based meta-algorithm.
AB  - Magnetic resonance imaging of pediatric brain provides valuable information for
      early brain development studies. Automated brain extraction is challenging due to
      the small brain size and dynamic change of tissue contrast in the developing
      brains. In this paper, we propose a novel Learning Algorithm for Brain Extraction
      and Labeling (LABEL) specially for the pediatric MR brain images. The idea is to
      perform multiple complementary brain extractions on a given testing image by
      using a meta-algorithm, including BET and BSE, where the parameters of each run
      of the meta-algorithm are effectively learned from the training data. Also, the
      representative subjects are selected as exemplars and used to guide brain
      extraction of new subjects in different age groups. We further develop a level
      set based fusion method to combine multiple brain extractions together with a
      closed smooth surface for obtaining the final extraction. The proposed method has
      been extensively evaluated in subjects of three representative age groups, such
      as neonate (less than 2 months), infant (1-2 years), and child (5-18 years).
      Experimental results show that, with 45 subjects for training (15 neonates, 15
      infant, and 15 children), the proposed method can produce more accurate brain
      extraction results on 246 testing subjects (75 neonates, 126 infants, and 45
      children), i.e., at average Jaccard Index of 0.953, compared to those by BET
      (0.918), BSE (0.902), ROBEX (0.901), GCUT (0.856), and other fusion methods such
      as Majority Voting (0.919) and STAPLE (0.941). Along with the largely-improved
      computational efficiency, the proposed method demonstrates its ability of
      automated brain extraction for pediatric MR images in a large age range.

PMID- 22634861
TI  - A K-means multivariate approach for clustering independent components from
      magnetoencephalographic data.
AB  - Independent component analysis (ICA) is typically applied on functional magnetic
      resonance imaging, electroencephalographic and magnetoencephalographic (MEG) data
      due to its data-driven nature. In these applications, ICA needs to be extended
      from single to multi-session and multi-subject studies for interpreting and
      assigning a statistical significance at the group level. Here a novel strategy
      for analyzing MEG independent components (ICs) is presented, Multivariate
      Algorithm for Grouping MEG Independent Components K-means based (MAGMICK). The
      proposed approach is able to capture spatio-temporal dynamics of brain activity
      in MEG studies by running ICA at subject level and then clustering the ICs across
      sessions and subjects. Distinctive features of MAGMICK are: i) the implementation
      of an efficient set of "MEG fingerprints" designed to summarize properties of MEG
      ICs as they are built on spatial, temporal and spectral parameters; ii) the
      implementation of a modified version of the standard K-means procedure to improve
      its data-driven character. This algorithm groups the obtained ICs automatically
      estimating the number of clusters through an adaptive weighting of the parameters
      and a constraint on the ICs independence, i.e. components coming from the same
      session (at subject level) or subject (at group level) cannot be grouped
      together. The performances of MAGMICK are illustrated by analyzing two sets of
      MEG data obtained during a finger tapping task and median nerve stimulation. The
      results demonstrate that the method can extract consistent patterns of spatial
      topography and spectral properties across sessions and subjects that are in good
      agreement with the literature. In addition, these results are compared to those
      from a modified version of affinity propagation clustering method. The
      comparison, evaluated in terms of different clustering validity indices, shows
      that our methodology often outperforms the clustering algorithm. Eventually,
      these results are confirmed by a comparison with a MEG tailored version of the
      self-organizing group ICA, which is largely used for fMRI IC clustering.

PMID- 22634862
TI  - Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A
      post mortem validation study.
AB  - Quantitative susceptibility mapping (QSM) is a novel technique which allows
      determining the bulk magnetic susceptibility distribution of tissue in vivo from
      gradient echo magnetic resonance phase images. It is commonly assumed that
      paramagnetic iron is the predominant source of susceptibility variations in gray
      matter as many studies have reported a reasonable correlation of magnetic
      susceptibility with brain iron concentrations in vivo. Instead of performing
      direct comparisons, however, all these studies used the putative iron
      concentrations reported in the hallmark study by Hallgren and Sourander (1958)
      for their analysis. Consequently, the extent to which QSM can serve to reliably
      assess brain iron levels is not yet fully clear. To provide such information we
      investigated the relation between bulk tissue magnetic susceptibility and brain
      iron concentration in unfixed (in situ) post mortem brains of 13 subjects using
      MRI and inductively coupled plasma mass spectrometry. A strong linear correlation
      between chemically determined iron concentration and bulk magnetic susceptibility
      was found in gray matter structures (r=0.84, p<0.001), whereas the correlation
      coefficient was much lower in white matter (r=0.27, p<0.001). The slope of the
      overall linear correlation was consistent with theoretical considerations of the
      magnetism of ferritin supporting that most of the iron in the brain is bound to
      ferritin proteins. In conclusion, iron is the dominant source of magnetic
      susceptibility in deep gray matter and can be assessed with QSM. In white matter
      regions the estimation of iron concentrations by QSM is less accurate and more
      complex because the counteracting contribution from diamagnetic myelinated
      neuronal fibers confounds the interpretation.

PMID- 22634863
TI  - A multidimensional magnetic resonance histology atlas of the Wistar rat brain.
AB  - We have produced a multidimensional atlas of the adult Wistar rat brain based on
      magnetic resonance histology (MRH). This MR atlas has been carefully aligned with
      the widely used Paxinos-Watson atlas based on optical sections to allow
      comparisons between histochemical and immuno-marker data, and the use of the
      Paxinos-Watson abbreviation set. Our MR atlas attempts to make a seamless
      connection with the advantageous features of the Paxinos-Watson atlas, and to
      extend the utility of the data through the unique capabilities of MR histology:
      a) ability to view the brain in the skull with limited distortion from shrinkage
      or sectioning; b) isotropic spatial resolution, which permits sectioning along
      any arbitrary axis without loss of detail; c) three-dimensional (3D) images
      preserving spatial relationships; and d) widely varied contrast dependent on the
      unique properties of water protons. 3D diffusion tensor images (DTI) at what we
      believe to be the highest resolution ever attained in the rat provide unique
      insight into white matter structures and connectivity. The 3D isotropic data
      allow registration of multiple data sets into a common reference space to provide
      average atlases not possible with conventional histology. The resulting
      multidimensional atlas that combines Paxinos-Watson with multidimensional MRH
      images from multiple specimens provides a new, comprehensive view of the
      neuroanatomy of the rat and offers a collaborative platform for future rat brain
      studies.

PMID- 22634864
TI  - Spatiotemporal re-organization of large-scale neural assemblies underlies
      bimanual coordination.
AB  - Bimanual coordination engages a distributed network of brain areas, the
      spatiotemporal organization of which has given rise to intense debates. Do
      bimanual movements require information processing in the same set of brain areas
      that are engaged by movements of the individual components (left and right
      hands)? Or is it necessary that other brain areas are recruited to help in the
      act of coordination? These two possibilities are often considered as mutually
      exclusive, with studies yielding support for one or the other depending on
      techniques and hypotheses. However, as yet there is no account of how the two
      views may work together dynamically. Using the method of Mode-Level Cognitive
      Subtraction (MLCS) on high density EEG recorded during unimanual and bimanual
      movements, we expose spatiotemporal reorganization of large-scale cortical
      networks during stable inphase and antiphase coordination and transitions between
      them. During execution of stable bimanual coordination patterns, neural dynamics
      were dominated by temporal modulation of unimanual networks. At instability and
      transition, there was evidence for recruitment of additional areas. Our study
      provides a framework to quantify large-scale network mechanisms underlying
      complex cognitive tasks often studied with macroscopic neurophysiological
      recordings.

PMID- 22634865
TI  - Regulation of T(H)2 development by CXCR5+ dendritic cells and lymphotoxin
      expressing B cells.
AB  - Although cognate encounters between antigen-bearing dendritic cells (DCs) that
      express the chemokine receptor CCR7 and CCR7(+) naive T cells take place in the T
      cell zone of lymph nodes, it is unknown whether the colocalization of DCs and T
      cells in the T cell area is required for the generation of effector cells. Here
      we found that after infection with an intestinal nematode, antigen-bearing DCs
      and CD4(+) T cells upregulated the chemokine receptor CXCR5 and localized
      together outside the T cell zone by a mechanism dependent on the chemokine
      CXCL13, B cells and lymphotoxin. Notably, lymphotoxin-expressing B cells, CXCR5
      expressing DCs and T cells, and CXCL13 were also necessary for development of
      interleukin 4 (IL-4)-producing type 2 helper T cells (T(H)2 cells), which
      suggests that T(H)2 differentiation can initiate outside the T cell zone.

PMID- 22634866
TI  - TGF-beta signaling to T cells inhibits autoimmunity during lymphopenia-driven
      proliferation.
AB  - T cell-specific deletion of the receptor for transforming growth factor-beta (TGF
      beta) mediated by Cre recombinase expressed early in T cell development leads to
      early-onset lethal autoimmune disease that cannot be controlled by regulatory T
      cells. However, when we deleted that receptor through the use of Cre driven by a
      promoter that is active much later in T cell development, adult mice in which
      most peripheral CD4(+) or CD8(+) T cells lacked the receptor for TGF-beta showed
      no signs of autoimmunity. Because of their enhanced responses to weak stimulation
      of the T cell antigen receptor, when transferred into lymphopenic recipients,
      naive TGF-beta-unresponsive T cells underwent much more proliferation and
      differentiation into effector cells and induced lymphoproliferative disease. We
      propose that TGF-beta signaling controls the self-reactivity of peripheral T
      cells but that in the absence of TGF-beta signals, an added trigger such as
      lymphopenia is needed to drive overt autoimmune disease.

PMID- 22634867
TI  - 4'-Hydroxyflavanone suppresses activation of sterol regulatory element-binding
      proteins and de novo lipid synthesis.
AB  - Sterol regulatory element-binding proteins (SREBPs) are major transcription
      factors that regulate the expression of genes involved in fatty acid and
      cholesterol biosynthesis. Here we show that 4'-hydroxyflavanone (4'-HF) impairs
      the fatty acid synthase promoter activity and reduces the activation of SREBPs
      and their target gene expression in human hepatoma Huh-7 cells. Moreover, 4'-HF
      suppresses de novo fatty acid and cholesterol synthesis. This study identifies 4'
      HF as an inhibitor of SREBP maturation and lipid synthesis, and provides evidence
      that 4'-HF may have major potential as a pharmaceutical preparation against
      hepatic steatosis and dyslipidemia.

PMID- 22634868
TI  - Sedentary time in relation to cardio-metabolic risk factors: differential
      associations for self-report vs accelerometry in working age adults.
AB  - BACKGROUND: Sedentary behaviour has been proposed to be detrimentally associated
      with cardio-metabolic risk independently of moderate to vigorous physical
      activity (MVPA). However, it is unclear how the choice of sedentary time (ST)
      indicator may influence such associations. The main objectives of this study were
      to examine the associations between ST and a set of cardio-metabolic risk factors
      [waist, body mass index (BMI), systolic and diastolic blood pressure, total and
      high-density lipoprotein cholesterol, glycated haemoglobin] and whether these
      associations differ depending upon whether ST is assessed by self-report or
      objectively by accelerometry. METHODS: Multiple linear regression was used to
      examine the above objectives in a cross-sectional study of 5948 adults (2669 men)
      aged 16-65 years with self-reported measures of television time, other
      recreational sitting and occupational sitting or standing. In all, 1150 (521 men)
      participants had objective (accelerometry) data on ST as well. RESULTS: Total
      self-reported ST showed multivariable-adjusted (including for MVPA) associations
      with BMI [(unstandardized beta coefficients corresponding to the mean difference
      per 10 min/day greater ST: 0.035 kg/m(2); 95% CI: 0.027-0.044), waist
      circumference (0.083 cm; 0.062-0.105), systolic (0.024 mmHg; 0.000-0.049) and
      diastolic blood pressure (0.023 mmHg; 0.006-0.040) and total cholesterol (0.004
      mmol/l; 0.001-0.006)]. Similar associations were observed for TV time, whereas
      non-TV self-reported ST showed consistent associations with the two adiposity
      proxies (BMI/waist circumference) and total cholesterol. Accelerometry-assessed
      ST was only associated with total cholesterol (0.010 mmol/l; 0.001-0.018).
      CONCLUSIONS: In this study, ST was associated consistently with cardio-metabolic
      risk only when it was measured by self-report.

PMID- 22634870
TI  - Identification of two mutations (F758W and F758Y) in the N-methyl-D-aspartate
      receptor glycine-binding site that selectively prevent competitive inhibition by
      xenon without affecting glycine binding.
AB  - BACKGROUND: Xenon is a general anesthetic with neuroprotective properties. Xenon
      inhibition at the glycine-binding site of the N-Methyl-D-aspartate (NMDA)
      receptor mediates xenon neuroprotection against ischemic injury in vitro. Here we
      identify specific amino acids important for xenon binding to the NMDA receptor,
      with the aim of finding silent mutations that eliminate xenon binding but leave
      normal receptor function intact. METHODS: Site-directed mutagenesis was used to
      mutate specific amino-acids in the GluN1 subunit of rat NMDA receptors. Mutant
      GluN1/GluN2A receptors were expressed in HEK 293 cells and were assessed
      functionally using patch-clamp electrophysiology. The responses of the mutant
      receptors to glycine and anesthetics were determined. RESULTS: Mutation of
      phenylalanine 758 to an aromatic tryptophan or tyrosine left glycine affinity
      unchanged, but eliminated xenon binding without affecting the binding of
      sevoflurane or isoflurane. CONCLUSIONS: These findings confirm xenon binds to the
      glycine site of the GluN1 subunit of the NMDA receptor and indicate that
      interactions between xenon and the aromatic ring of the phenylalanine 758 residue
      are important for xenon binding. Our most important finding is that we have
      identified two mutations, F758W and F758Y, that eliminate xenon binding to the
      NMDA receptor glycine site without changing the glycine affinity of the receptor
      or the binding of volatile anesthetics. The identification of these selective
      mutations will allow knock-in animals to be used to dissect the mechanism(s) of
      xenon's neuroprotective and anesthetic properties in vivo.

PMID- 22634869
TI  - Sedentary behaviour and cardiovascular disease: a review of prospective studies.
AB  - BACKGROUND: Current estimates from objective accelerometer data suggest that
      American adults are sedentary for ~7.7 h/day. Historically, sedentary behaviour
      was conceptualized as one end of the physical activity spectrum but is
      increasingly being viewed as a behaviour distinct from physical activity.
      METHODS: Prospective studies examining the associations between screen time
      (watching television, watching videos and using a computer) and sitting time and
      fatal and non-fatal cardiovascular disease (CVD) were identified. These
      prospective studies relied on self-reported sedentary behaviour. RESULTS: The
      majority of prospective studies of screen time and sitting time has shown that
      greater sedentary time is associated with an increased risk of fatal and non
      fatal CVD. Compared with the lowest levels of sedentary time, risk estimates
      ranged up to 1.68 for the highest level of sitting time and 2.25 for the highest
      level of screen time after adjustment for a series of covariates, including
      measures of physical activity. For six studies of screen time and CVD, the
      summary hazard ratio per 2-h increase was 1.17 (95% CI: 1.13-1.20). For two
      studies of sitting time, the summary hazard ratio per 2-h increase was 1.05 (95%
      CI: 1.01-1.09). CONCLUSIONS: Future prospective studies using more objective
      measures of sedentary behaviour might prove helpful in quantifying better the
      risk between sedentary behaviour and CVD morbidity and mortality. This budding
      science may better shape future guideline development as well as clinical and
      public health interventions to reduce the amount of sedentary behaviour in modern
      societies.

PMID- 22634871
TI  - Utilization of critical care services among patients undergoing total hip and
      knee arthroplasty: epidemiology and risk factors.
AB  - BACKGROUND: A paucity of data exist on the use of critical care services (CCS)
      among hip and knee arthroplasty patients. The authors sought to identify the
      incidence and risk factors for the use of CCS among these patients and compare
      the characteristics and outcomes of patients who require CCS to those who do not.
      METHODS: The authors analyzed hospital discharge data of patients who underwent
      primary hip or knee arthroplasty in approximately 400 United States hospitals
      between 2006 and 2010. Patient and healthcare system-related demographics for
      admitted patients requiring CCS were compared with those who did not. Differences
      in outcomes, including mortality, complications, disposition status, and hospital
      charges, were analyzed. Regression analysis was performed to identify risk
      factors for requiring CCS. RESULTS: A total of 528,495 patients underwent primary
      total hip (n = 172,467, 33%) and knee arthroplasty (n = 356,028, 67%). Of these,
      3% required CCS. On average, CCS patients were older and had a higher comorbidity
      burden than did patients not requiring CCS. CCS patients experienced more
      complications, had longer hospital stays and higher costs, and were less likely
      to be discharged home than were non-CCS patients. Risk factors with increased
      odds for requiring CCS included advanced age, use of general versus neuraxial
      anesthesia, and the presence of postoperative cardiopulmonary complications.
      CONCLUSIONS: Approximately 1 of 30 patients undergoing total joint arthroplasty
      requires CCS. Given the large number of these procedures performed annually,
      anesthesiologists, orthopedic surgeons, critical care physicians, and
      administrators should be aware of the attendant risks this population represents
      and allocate resources accordingly.

PMID- 22634872
TI  - Regulation of peripheral clock to oscillation of substance P contributes to
      circadian inflammatory pain.
AB  - BACKGROUND: The daily fluctuations of many physiologic and behavioral parameters
      are differentially influenced by either central or peripheral clocks in mammals.
      Since substance P (SP) oscillates in some brain tissues and plays an
      indispensable role in modulating inflammatory pain at the spinal level, we
      speculated that SP mediates circadian nociception transmission at the spinal
      level. METHODS: In the present study behavioral observation, real-time polymerase
      chain reaction, luciferase assay, chromatin immunoprecipitation, and
      immunohistochemistry stain methods were used to investigate the role of SP in the
      spinal circadian nociception transmission and its regulation mechanism. RESULTS:
      Our results showed that under transcriptional regulation of BMAL1:CLOCK
      heterodimers, SP's coding gene Tac1 expression oscillates in dorsal root ganglion
      (n = 36), but not in the spinal dorsal horn. Further, the expression of SP cycled
      in the spinal dorsal horn, and this rhythmicity was potentially determined by
      circadian expression of Tac1 in dorsal root ganglion. Furthermore, the variation
      of SP expression induced by formalin was fluctuated in a similar rhythm to
      behavioral nociceptive response induced by formalin (n = 48); and the nociceptive
      behavioral circadian rhythm could be abolished through blockade of the SP
      Neurokinin 1 receptor pathway (n = 70). Lastly, the variations of spinal SP
      expression and behavioral nociceptive response were in step, and both were
      changed by the deletion mutation of clock gene. CONCLUSIONS: We conclude that
      spinal SP probably plays a pivotal role in modulating circadian inflammatory pain
      and suggest that peripheral circadian-regulated signaling is potentially an
      essential pathway for circadian nociceptive transmission.

PMID- 22634873
TI  - Age-dependent role of microvascular endothelial and polymorphonuclear cells in
      lipopolysaccharide-induced acute kidney injury.
AB  - BACKGROUND: The incidence of acute kidney injury following severe sepsis is
      higher in the elderly. We hypothesized that microvascular endothelium is "primed"
      by aging and that sepsis represents a "second hit," resulting in more severe
      microvascular complications. METHODS: Three- and 18-months-old mice were
      intraperitoneally injected with 1,500 EU/g body weight lipopolysaccharide and
      sacrificed after 8 h. Flow cytometry and myeloperoxidase ELISA determined
      neutrophils in plasma. Quantitative reverse transcription polymerase chain
      reaction was used to analyze messenger ribonucleic acid levels of cell adhesion
      molecules P-selectin and E-selectin, vascular cell adhesion protein-1,
      intercellular adhesion molecule-1, angiopoietin receptor TIE-2, and angiopoietins
      Ang1 and Ang2. In kidney tissue we assessed neutrophil influx and E-selectin
      protein expression. Neutrophils were depleted with the monoclonal antibody NIMP.
      RESULTS: At basal conditions, microvascular endothelial cell activation status
      was similar in both groups, except for a higher Ang-2 expression (P < 0.05) in
      the kidney of aged mice. Lipopolysaccharide-induced increase in neutrophil count
      was higher in old (3.3-fold change) compared with young mice (2.2-fold change).
      Messenger ribonucleic acid analysis showed higher upregulation of P- and E
      selectin (P = 0.0004, P = 0.0007) after lipopolysaccharide administration in
      kidneys of elderly mice, which was confirmed at the protein level for E-selectin.
      Renal neutrophil influx in lipopolysaccharide-treated aged mice was increased
      (2.5-fold induction in aged and 2.1-fold in young, P < 0.0001). Polymorphonuclear
      cell depletion exaggerated the lipopolysaccharide-induced kidney injury.
      CONCLUSION: Ang-2 is increased in older mice, which might cause priming of the
      endothelial cells. Endothelium responded by a more extensive increase in
      expression of P- and E-selectin in older mice and increased polymorphonuclear
      cell influx.

PMID- 22634874
TI  - Exchange bias effect in partially oxidized amorphous Fe-Ni-B based metallic glass
      nanostructures.
AB  - The magnetic properties of amorphous Fe-Ni-B based metallic glass nanostructures
      were investigated. The nanostructures underwent a spin-glass transition at
      temperatures below 100 K and revealed an irreversible temperature following the
      linear de Almeida-Thouless dependence. When the nanostructures were cooled below
      25 K in a magnetic field, they exhibited an exchange bias effect with enhanced
      coercivity. The observed onset of exchange bias is associated with the
      coexistence of the spin-glass phase along with the appearance of another spin
      glass phase formed by oxidation of the structurally disordered surface layer,
      displaying a distinct training effect and cooling field dependence. The latter
      showed a maximum in exchange bias field and coercivity, which is probably due to
      competing multiple equivalent spin configurations at the boundary between the two
      spin-glass phases.

PMID- 22634876
TI  - Accurate diagnosis of cerebral malaria: a role for parasite histidine-rich
      protein 2?

PMID- 22634875
TI  - Magnitude and breadth of the neutralizing antibody response in the RV144 and
      Vax003 HIV-1 vaccine efficacy trials.
AB  - BACKGROUND: A recombinant canarypox vector expressing human immunodeficiency
      virus type 1 (HIV-1) Gag, Pro, and membrane-linked gp120 (vCP1521), combined with
      a bivalent gp120 protein boost (AIDSVAX B/E), provided modest protection against
      HIV-1 infection in a community-based population in Thailand (RV144 trial). No
      protection was observed in Thai injection drug users who received AIDSVAX B/E
      alone (Vax003 trial). We compared the neutralizing antibody response in these 2
      trials. METHODS: Neutralization was assessed with tier 1 and tier 2 strains of
      virus in TZM-bl and A3R5 cells. RESULTS: Neutralization of several tier 1 viruses
      was detected in both RV144 and Vax003. Peak titers were higher in Vax003 and
      waned rapidly in both trials. The response in RV144 was targeted in part to V3 of
      gp120.vCP1521 priming plus 2 boosts with gp120 protein was superior to 2 gp120
      protein inoculations alone, confirming a priming effect for vCP1521. Sporadic
      weak neutralization of tier 2 viruses was detected only in Vax003 and A3R5 cells.
      CONCLUSION: The results suggest either that weak neutralizing antibody responses
      can be partially protective against HIV-1 in low-risk heterosexual populations or
      that the modest efficacy seen in RV144 was mediated by other immune responses,
      either alone or in combination with neutralizing antibodies.

PMID- 22634878
TI  - Interleukin 6, RANKL, and osteoprotegerin expression by chikungunya virus
      infected human osteoblasts.

PMID- 22634877
TI  - Plasma concentrations of parasite histidine-rich protein 2 distinguish between
      retinopathy-positive and retinopathy-negative cerebral malaria in Malawian
      children.
AB  - BACKGROUND: Brain histology and ophthalmoscopy suggest that approximately 25% of
      children with World Health Organization-defined cerebral malaria (CM) have a
      nonmalarial cause of death. Misclassification complicates clinical care,
      confounds studies of association, and may obfuscate successes in malaria control.
      Retinopathy predicts intracerebral parasite sequestration with >90% sensitivity
      and specificity, but detecting retinopathy requires well-trained personnel and
      expensive equipment. METHODS: We investigated the utility of plasma
      concentrations of parasite histidine-rich protein 2 (pHRP2), a Plasmodium
      specific protein, as a predictor of intracerebral parasite sequestration at
      autopsy and of malaria retinopathy on clinical examination in patients with
      clinically defined CM. RESULTS: In 64 autopsy cases, 47 of whom had histological
      evidence of sequestration, the sensitivity and specificity of a plasma pHRP2
      level of >1700 ng/mL were 98% and 94%, respectively, and the area under the
      receiver operating characteristic (AUROC) curve was 0.98. In a separate,
      prospectively studied group of 101 children with clinically defined CM, of whom
      71 had retinopathy, the same pHRP2 cutoff predicted retinopathy-positivity with a
      sensitivity of 90% and specificity of 87% (AUROC, 0.90). CONCLUSIONS: Elevated
      plasma pHRP2 concentrations can identify Malawian children with histologically
      confirmed or retinopathy-positive CM and is a more field-friendly approach to
      confirming the diagnosis than post mortem sampling or ophthalmoscopy.

PMID- 22634880
TI  - Pharmacodynamics of voriconazole in a dynamic in vitro model of invasive
      pulmonary aspergillosis: implications for in vitro susceptibility breakpoints.
AB  - BACKGROUND: Voriconazole is a first-line agent for the treatment of invasive
      pulmonary aspergillosis (IPA). There are increasing reports of Aspergillus
      fumigatus isolates with reduced susceptibility to voriconazole. METHODS: An in
      vitro dynamic model of IPA was developed that enabled simulation of human-like
      voriconazole pharmacokinetics. Galactomannan was used as a biomarker. The
      pharmacodynamics of voriconazole against wild-type and 3 resistant strains of A.
      fumigatus were defined. The results were bridged to humans to provide decision
      support for setting breakpoints for voriconazole using Clinical Laboratory
      Standards Institute (CLSI) and European Committee of Antimicrobial Susceptibility
      Testing (EUCAST) methodologies. RESULTS: Isolates with higher minimum inhibitory
      concentrations (MICs) required higher area under the concentration time curves
      (AUCs) to achieve suppression of galactomannan. Using CLSI and EUCAST
      methodologies, the AUC:MIC values that achieved suppression of galactomannan were
      55 and 32.1, respectively. Using CLSI and EUCAST methodologies, the trough
      concentration:MIC values that achieved suppression of galactomannan were 1.68 and
      1, respectively. Potential CLSI breakpoints for voriconazole are <= 0.5 mg/L for
      susceptible and >1 mg/L for resistant. Potential EUCAST breakpoints for
      voriconazole are <=1 mg/L for susceptible and >2 mg/L for resistant. CONCLUSIONS:
      This dynamic model of IPA is a useful tool to address many remaining questions
      related to antifungal treatment of Aspergillus spp.

PMID- 22634881
TI  - Intestinal parasitism and socio-environmental factors among Mbya-Guarani Indians,
      Porto Alegre, Rio Grande do Sul, Brazil.
AB  - Disturbing data reveal the prevalence of intestinal parasites and their
      relationship with socio-environmental factors among Mbya-Guarani Indians. The
      prevalence was determined by spontaneous sedimentation in water, centrifugation
      floatation, and Kato-Katz. A socioeconomic questionnaire was submitted to each
      family. The overall prevalence of intestinal parasites was 88.7%, and 45.5% were
      polyparasitized. There was 90.5% prevalence of enteric parasites in children (1
      12- year-old), and 85% among 13-65-year-old individuals, indicating that both age
      groups are extensively parasitized. The parasite load was low to moderate for
      geohelminths and 75% of the families did not have latrine, thus the practice of
      defecation occurred outdoors. These findings suggest that the multiple intestinal
      parasitism in the Mbya-Guarani community is high to the point of being the rule,
      and that it relates essentially to the traditional lifestyle and health habits.
      It is urgently necessary to implement the association of anti-parasitic treatment
      with sanitation improvement. This should be done simultaneously with health
      education activities for this population.

PMID- 22634882
TI  - HTLV-1/2 seroprevalence and coinfection rate in Brazilian first-time blood
      donors: an 11-year follow-up.
AB  - The seroprevalence and geographic distribution of HTLV-1/2 among blood donors are
      extremely important to transfusion services. We evaluated the seroprevalence of
      HTLV-1/2 infection among first-time blood donor candidates in Ribeirao Preto city
      and region. From January 2000 to December 2010, 1,038,489 blood donations were
      obtained and 301,470 were first-time blood donations. All samples were screened
      with serological tests for HTLV-1/2 using enzyme immunoassay (EIA). In addition,
      the frequency of coinfection with hepatitis B virus (HBV), hepatitis C virus
      (HCV), human immunodeficiency virus (HIV), Chagas disease (CD) and syphilis was
      also determined. In-house PCR was used as confirmatory test for HTLV-1/2. A total
      of 296 (0.1%) first-time donors were serologically reactive for HTLV-1/2.
      Confirmatory PCR of 63 samples showed that 28 were HTLV-1 positive, 13 HTLV-2
      positive, 19 negative and three indeterminate. Regarding HTLV coinfection rates,
      the most prevalent was with HBV (51.3%) and HCV (35.9%), but coinfection with
      HIV, CD and syphilis was also detected. The real number of HTLV-infected
      individual and coinfection rate in the population is underestimated and
      epidemiological studies like ours are very informative.

PMID- 22634883
TI  - Rickettsia parkeri: a Rickettsial pathogen transmitted by ticks in endemic areas
      for spotted fever rickettsiosis in southern Uruguay.
AB  - At first Rickettsia conorii was implicated as the causative agent of spotted
      fever in Uruguay diagnosed by serological assays. Later Rickettsia parkeri was
      detected in human-biting Amblyomma triste ticks using molecular tests. The
      natural vector of R. conorii, Rhipicephalus sanguineus, has not been studied for
      the presence of rickettsial organisms in Uruguay. To address this question, 180
      R. sanguineus from dogs and 245 A. triste from vegetation (flagging) collected in
      three endemic localities were screened for spotted fever group (SFG)
      rickettsiosis in southern Uruguay. Tick extracted DNA pools were subjected to PCR
      using primers which amplify a fragment of the rickettsial gltA gene. Positive
      tick DNA pools with these primers were subjected to a second PCR round with
      primers targeting a fragment of the ompA gene, which is only present in SFG
      rickettsiae. No rickettsial DNA was detected in R. sanguineus. However, DNA pools
      of A. triste were found to be positive for a rickettsial organism in two of the
      three localities, with prevalences of 11.8% to 37.5% positive pools. DNA
      sequences generated from these PCR-positive ticks corresponded to R. parkeri.
      These findings, joint with the aggressiveness shown by A. triste towards humans,
      support previous data on the involvement of A. triste as vector of human
      infections caused by R. parkeri in Uruguay.

PMID- 22634884
TI  - Characterization of the molluscicidal activity of Bauhinia variegata and Mimusops
      elengi plant extracts against the fasciola vector Lymnaea acuminata.
AB  - The molluscicidal activity of Bauhinia variegata leaf and Mimusops elengi bark
      was studied against vector snail Lymnaea acuminata. The toxicity of both plants
      was time and concentration-dependent. Among organic extracts, ethanol extracts of
      both plants were more toxic. Toxicity of B. variegata leaf ethanolic extract (96h
      LC50- 14.4 mg/L) was more pronounced than M. elengi bark ethanolic extract (96h
      LC50-15.0 mg/L). The 24h LC50 of column purified fraction of B. variegata and M.
      elengi bark were 20.3 mg/L and 18.3 mg/L, respectively. Saponin and quercetin
      were characterized and identified as active molluscicidal component. Co-migration
      of saponin (Rf 0.48) and quercetin (Rf 0.52) with column purified bark of M.
      elengi and leaf of B. variegata on thin layer chromatography demonstrate same Rf
      value i.e. 0.48 and 0.52, respectively. The present study clearly indicates the
      possibility of using M. elengi and/or B. variegata as potent molluscicide.

PMID- 22634885
TI  - Discrepancies and consequences of indirect hemagglutination, indirect
      immunofluorescence and ELISA tests for the diagnosis of Chagas disease.
AB  - Using the indirect hemagglutination (IH), indirect immunofluorescence (IIF) and
      enzyme linked immunosorbent assay (ELISA) tests for the diagnosis of Chagas
      disease, 4000 serum samples were examined. This study was conducted with
      different purposes: clinical interest, research support and parasitological
      monitoring of those patients with Chagas disease who were treated with heart
      transplantations. The tests occurred without patient selection and in accordance
      with the medical requests. The results showed discrepancies and brought about
      several questions, considering the different results that all three methods
      showed when considered together. What was found brought about concerns and we
      suggest the adoption of different measures, aiming to avoid these mismatches in
      the context of this disease.

PMID- 22634886
TI  - IgG antibody responses in mice coinfected with Toxocara canis and other helminths
      or protozoan parasites.
AB  - The immune response expressed by IgG antibodies in BALB/c mice experimentally
      infected with Toxocara canis, was studied with the aim of verifying the possible
      in vivo cross-reactivity between antigens of T. canis and other parasites
      (Ascaris suum, Taenia crassiceps, Schistosoma mansoni, Strongyloides
      venezuelensis and Toxoplasma gondii). Experiments included three groups of mice:
      one infected only by T. canis, another with one of the other species of parasites
      and a third concomitantly infected with T. canis and the other species in
      question. Animals were bled by orbital plexus at 23, 38 and 70 days post
      infection (p.i.). Sera were analyzed for anti-Toxocara antibodies by ELISA and
      Immunoblotting, using excretion-secretion antigens (ES), obtained from culture of
      third-stage larvae of T. canis. For all experiments a control group comprised by
      ten non-infected mice was used. Only in the case of A. suum infection, in these
      experimental conditions, the occurrence of cross-reactivity with T. canis was
      observed. However, in the case of co-infection of T. canis - S. mansoni, T. canis
      - S. venezuelensis and T. canis - T. crassiceps the production of anti-Toxocara
      antibodies was found at levels significantly lower than those found in mice
      infected with T. canis only. Co-infection with S. mansoni or S. venezuelensis
      showed lower mortality rates compared to what occurred in the animals with single
      infections. Results obtained in mice infected with T. canis and T. gondii showed
      significant differences between the mean levels of the optical densities of
      animals infected with T. canis and concomitantly infected with the protozoan only
      in the 23rd day p.i.

PMID- 22634887
TI  - Amplification of the flgE gene provides evidence for the existence of a Brazilian
      borreliosis.
AB  - INTRODUCTION: The symptoms of Brazilian borreliosis resemble the clinical
      manifestations of Lyme disease (LD). However, there are differences between the
      two in terms of epidemiological and laboratory findings. Primers usually employed
      to diagnose LD have failed to detect Borrelia strains in Brazil. OBJECTIVE: We
      aimed to identify the Brazilian Borrelia using a conserved gene that synthesizes
      the flagellar hook (flgE) of Borrelia burgdorferi sensu lato. METHOD: Three
      patients presenting with erythema migrans and positive epidemiological histories
      were recruited for the study. Blood samples were collected, and the DNA was
      extracted by commercial kits. RESULTS: The gene flgE was amplified from DNA of
      all selected patients. Upon sequencing, these positive samples revealed 99%
      homology to B. burgdorferi flgE. CONCLUSION: These results support the existence
      of borreliosis in Brazil. However, it is unclear whether this borreliosis is
      caused by a genetically modified B. burgdorferi sensu stricto or by a new species
      of Borrelia spp.

PMID- 22634888
TI  - Expression of TLR2 and TLR4 in lesions of patients with tegumentary American
      leishmaniasis.
AB  - OBJECTIVES: The aim of this study was to describe the pattern of expression of
      Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in skin biopsies of
      patients with American tegumentary leishmaniasis (ATL) caused by Leishmania
      braziliensis. METHODS: This prospective study evaluated 12 patients with ATL
      caused by Leishmania braziliensis confirmed by polymerase chain reaction.
      Immunohistochemistry was performed to determine the expression of TLR2 and TLR4.
      The number of NK cells, dendritic cells and macrophages in the tissue were
      calculated. The cytokine expression was determined using the anti-TNF-alpha, anti
      IFN-Gamma, anti-IL-1 and anti-IL-6. Double immunostaining reactions were used to
      determine the cell expressing TLR2 and TLR4. RESULTS: The numbers of cells
      expressing TLR2 and TLR4 were 145.48 +/- 82.46 cell/mm2 and 3.26 +/- 4.11
      cell/mm2 respectively (p < 0.05). There was no correlation of TLR2 and TLR4 with
      the amount of cytokines and the number of NK cells, dendritic cells or
      macrophages. The double immunostaining revealed that TLR2 was expressed by
      macrophages. CONCLUSION: In human cutaneous leishmaniasis caused by Leishmania
      braziliensis, TLR2 is the most common TLR expressed during active disease, mainly
      by macrophages although without correlation with the amount of cytokines and
      number of cells.

PMID- 22634889
TI  - Preliminary study towards a novel experimental model to study localized cutaneous
      leishmaniasis caused by Leishmania (Leishmania) mexicana.
AB  - There is not an experimental model of localized cutaneous leishmaniasis (LCL)
      caused by Leishmania (Leishmania) mexicana. The aim of the present study was to
      characterize the clinical and histological features of Peromyscus yucatanicus
      experimentally infected with L. (L.) mexicana. A total of 54 P. yucatanicus
      (groups of 18) were inoculated with 1x10(6) promastigotes of L. (L.) mexicana in
      the base of the tail. They were euthanized at three and six months post
      experimental infection. The control group was inoculated with RPMI-1640. The
      predominant clinical sign observed was a single ulcerated lesion in 27.77% (5/18)
      and in 11.11% (2/18) P. yucatanicus at three and six months respectively. The
      histological pattern described as chronic granulomatous inflammation with or
      without necrosis was found in 7/7 (100%) biopsies of euthanized P. yucatanicus at
      three (n = 5) and six (n = 2) months, respectively. These results resembled
      clinical and histological features caused by L. (L.) mexicana in humans, and
      support the possibility to employ P. yucatanicus as a novel experimental model to
      study LCL caused by this parasite.

PMID- 22634890
TI  - Mycotic aneurysm of the tibioperoneal trunk: a first manifestation of an infected
      endocarditis.
AB  - Infrapopliteal mycotic aneurysm resulting from endocarditis is rare, with only a
      few reported cases. We describe the case of a 28-year-old male patient who was
      suffering with pain and edema in the right leg. The ultrasound revealed an
      aneurysm of the right tibioperoneal trunk and a deep vein thrombosis (DVT). The
      patient was admitted and developed acute congestive heart failure, being
      diagnosed with possible endocarditis. A pseudo-aneurysm was revealed by
      arteriography. Aggressive antibiotic treatment was initiated, and open surgery
      confirmed a mycotic pseudo-aneurysm of the tibioperoneal trunk. To our knowledge,
      this is the 8th case reported of an infected aneurysm in this particular
      location.

PMID- 22634891
TI  - Ectopic dirofilariosis in two dogs from Rio de Janeiro state, Brazil.
AB  - Report of two canine dirofilariosis cases of ectopic location in the state of Rio
      de Janeiro. This is the first report of erratic migration for this parasitosis in
      dogs in the state, calling attention to the short period of time between the two
      cases. The fact that the area is endemic for this parasite, its zoonotic
      potential and the report of human cases in the state, demonstrates that
      authorities should be alerted to the control programs of dirofilariosis along
      with the pathogenic profile of the infections.

PMID- 22634892
TI  - It's all in the timing: ovulation induction in the mare.

PMID- 22634893
TI  - Selective breeding: making the welfare consequences clear.

PMID- 22634894
TI  - Continued presentation of cases of Schmallenberg virus in sheep in England.

PMID- 22634895
TI  - Herpesvirus infection in equids.

PMID- 22634896
TI  - Hereditary ataxia in Jack Russell terriers in the UK.

PMID- 22634898
TI  - High pressure enhances the effect of hyperthermia in intraperitoneal chemotherapy
      with oxaliplatin: an experimental study.
AB  - BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
      (HIPEC) achieve good results in selected patients with peritoneal carcinomatosis.
      High intra-abdominal pressure could enhance the penetration of chemotherapy
      drugs. The aim of this study was to compare the effects of high pressure and
      hyperthermia when used separately and when combined in terms of blood and tissue
      absorption of oxaliplatin in a swine model of intraperitoneal chemotherapy.
      METHODS: Four groups of 5 pigs each underwent laparotomy and open intraperitoneal
      chemotherapy with oxaliplatin at a constant concentration (150 mg/L) for 30
      minutes in normothermia and atmospheric pressure (group 1), or hyperthermia (42
      degrees C) and atmospheric pressure (group 2), or normothermia and high pressure
      (25 cm H2O) (group 3), or hyperthermia and high pressure (group 4). High pressure
      was achieved thorough a water column over the abdomen. Systemic absorption and
      abdominal tissue mapping of the penetration of oxaliplatin in each group were
      studied. RESULTS: Blood concentrations of oxaliplatin were similar in the
      different groups. Hyperthermia achieved higher concentrations in visceral
      surfaces (P = 0.0014), but not in parietal surfaces. High pressure enhanced
      diffusion of the drug in both the visceral and parietal peritoneum (P = 0.0058
      and P = 0.0044, respectively). The combination of hyperthermia and high pressure
      significantly increased the penetration of oxaliplatin and achieved the highest
      tissue concentrations (10.39 mg/kg vs 5.48 mg/kg; P = 0.00001 in the visceral
      peritoneum, and 66.16 mg/kg vs 35.62 mg/kg; P = 0.0003 in the parietal
      peritoneum). CONCLUSIONS: Open high-pressure HIPEC with oxaliplatin is feasible
      in the pig. Hyperthermia enhances diffusion in the visceral peritoneum, whereas
      high pressure is effective in the visceral and parietal peritoneum. The
      combination of the two achieves the highest tissue concentrations of oxaliplatin.

PMID- 22634899
TI  - Past history of skin infection and risk of surgical site infection after elective
      surgery.
AB  - OBJECTIVE: To identify baseline patient characteristics associated with increased
      susceptibility to surgical site infection (SSI) after elective surgery.
      BACKGROUND: The Center for Medicare and Medicaid Services considers SSI to be
      preventable through adherence to current infection control practices; however,
      the etiology of wound infection is incompletely understood. METHODS: Prospective
      cohort study involving patients undergoing cardiac, vascular, craniotomy, and
      spinal surgery at 2 academic medical centers in Baltimore, MD. A comprehensive
      medical history was obtained at baseline, and participants were followed for 6
      months using active inpatient and outpatient surveillance for deep SSI and
      infectious death. Infection control best practices were monitored
      perioperatively. The relative risk of SSI/infectious death was determined
      comparing those with versus those without a past medical history of skin
      infection using Cox proportional hazards models. RESULTS: Of 613 patients (mean
      [SD] = 62.3 [11.5] years; 42.1% women), 22.0% reported a history of skin
      infection. The cumulative incidence of deep SSI/infectious death was 6.7% versus
      3.1% for those with and without a history of skin infection, respectively
      (unadjusted hazard ratio (HR) = 2.25; 95% confidence interval (95% CI), 0.98
      5.14; P = 0.055). Risk estimates increased after adjustments for demographic and
      socioeconomic variables (HR = 2.82; 95% CI, 1.18-6.74; P = 0.019) and after
      propensity score adjustment for all potential confounders (HR = 3.41; 95% CI,
      1.36-8.59; P = 0.009). Adjustments for intraoperative infection risk factors and
      adherence to infection control best practice metrics had no impact on risk
      estimates. CONCLUSIONS: A history of skin infection identified a state of
      enhanced susceptibility to SSI at baseline that is independent of traditional SSI
      risk factors and adherence to current infection control practices.

PMID- 22634900
TI  - Updated literature on povidone-iodine for control of surgical site infections.

PMID- 22634902
TI  - Role of laparoscopic surgery in treatment of infertility.
AB  - The role of laparoscopy in assisted reproduction is disputed by many. A rising
      problem of infertility is battled by an increasing number of centres for
      reproductive medicine in the region. Nevertheless, there is a large number of
      indications and conditions where laparoscopic surgery should not be avoided as a
      therapeutic choice or an aid in assisted reproductive techniques (ART). The
      number of centres where laparoscopic surgery is performed is significantly higher
      than the number of reproductive centres; a number of gynaecologists educated in
      laparoscopic gynaecology is growing, making it more available for patients.

PMID- 22634903
TI  - Starch for health.
AB  - It is well established that part of starch is resistant to human amylases and
      escapes undigested to large bowel. This fraction of starch is resistant starch.
      Recent studies have shown that resistant starch may be a substrate for bacterial
      flora of the colon and serves as prebiotic. Short chain fatty acids (SCFA)
      produced by colonic fermentation of resistant starch may have impact on colonic
      function and health of humans. This paper summarises current knowledge on
      properties and health impact of resistant starch.

PMID- 22634904
TI  - Medical applications of wireless sensor networks - current status and future
      directions.
AB  - In recent years a significant development of BASN (Body Area Sensor Networks) as
      a special subclass of WSN (Wireless Sensor Networks) has emerged. These networks
      have enabled a rapid development of telemedicine systems, which provide remote
      monitoring of patients and their vital parameters. The article gives a short
      overview of the BASN networks. Furthermore, a general system architecture of
      telemedicine systems is proposed. The proposed architecture includes a local
      sensory area, a communication network area and an institutional network area. It
      also provides the security and privacy of patient-related data. Furthermore, the
      article surveys some existing telemedicine systems. Finally, some current
      problems are explained and the directions for the future development of the
      telemedicine systems are given.

PMID- 22634905
TI  - Influence of short-term changes in sex hormones on serum concentrations of
      cellular adhesion molecules in young healthy women.
AB  - AIM: To determine if short-term changes in sex hormones (such as cyclic changes
      within the menstrual cycle) can influence the serum concentration of soluble cell
      adhesion molecules (CAMs). METHODS: Sixteen healthy young women with normal
      cycles participated in this study. Serum levels of sICAM-1, sVCAM-1 and E
      selectin were determined in three different phases of the menstrual cycle: a)
      early follicular (EF) phase, b) ovulatory (O) phase and c) midluteal (ML) phase,
      by standardized ELISA-based kits. To confirm the exact assessment of menstrual
      cycle phases, serum levels of estrogen, progesterone, LH and FSH were measured.
      RESULTS: There were significant oscillations in serum female sex hormones
      concentration over the cycle duration, as expected the level of estrogen (E2) and
      progesterone (PROG) was the lowest in EF phase, the highest E2 appeared in O
      phase, and both E2 and PROG were present in high concentrations during ML phase.
      There was a significant positive correlation between E2 and serum soluble ICAM -1
      concentrations (p=0,041, correlation coefficient 0,306). However, there was no
      significant change in other soluble CAMs concentration during the menstrual
      cycle. CONCLUSIONS: Results of our study suggest that short-term changes in
      female sex hormone levels could modulate expression of soluble ICAM-1, but not
      VCAM -1 or E-selectin in extent that would affect a young woman's health.

PMID- 22634906
TI  - The effect of intravenous vitamin C on the phosphorus level reduction in
      hemodialysis patients: a double blind randomized clinical trial.
AB  - AIM: The majority of hemodialysis patients are hyperphosphatemic.
      Hyperphosphatemia in these patients can lead to renal osteodystrophy, vascular
      calcification, cardiovascular events, and is independently associated with
      mortality risk. The aim of this study was to evaluate the effect of intravenous
      vitamin C on phosphorus level in hemodialysis patients. METHODS: Using a double
      blind randomized clinical trial, a total of 60 qualified hemodialysis patients
      were randomly allocated in two intervention and control groups and serum
      phosphorus, CRP, calcium, albumin and PTH levels were measured. At the end of
      each hemodialysis session, intervention group received vitamin C vial (500 mg/5
      cc) intravenously three times a week for 8 weeks and control group received
      normal saline in the same way. Data were collected before and after two months of
      treatment. Data were analyzed using independent t-test, paired t-test and chi
      square test. RESULTS: Vitamin C treated group had a significant decrease in
      phosphorus (p=0.01), CRP level (p=0.01) and Ca*P product (p=0.03). In contrast,
      there was no significant difference in phosphorous (p= 0.5) and CRP levels (p=
      0.6) and Ca*P product (p=0.7) in the control group. In addition, there was no
      statistically significant change in calcium (p=0.1), PTH (p=0.4) and albumin
      (p=0.4) levels in both groups. CONCLUSIONS: Intravenous vitamin C can
      significantly decrease phosphorus level in hemodialysis patients.

PMID- 22634907
TI  - Aortic flow propagation velocity as an early predictor of high coronary risk in
      hypertensive patients.
AB  - AIM: To assess the value of aortic flow propagation velocity (Vp) in detecting
      hypertensive patients with coronary risk. METHODS: The study included 120
      patients with hypertension. According to the 10-year risk of coronary heart
      disease the patients were categorized in the three groups: 10-year risk  < 10%
      (I),10 - year risk=%10 - 20 (II), and 10-year risk > 20% (III). The aortic flow
      propagation velocity (Vp) was measured from descending aorta with color M-mode
      echoardiography. The slope of the first aliasing contour was accepted as Vp. It
      was compared with Framingham coronary risk score, carotid intima media thickness
      and high sensitive C-reactive protein. Twelve patients were excluded from the
      study due to poor acoustic window. RESULTS: The Vp was significantly lower
      (p<0.001), carotid intima media thickness and high sensitive C-reactive protein
      was significantly higher in group III (p=0.002 and p=0.014). The area under ROC
      curve of Vp, carotid intima media thickness and high sensitive C-reactive protein
      were 0.890, 0,700 and 0.664, respectively. There was a significant inverse
      relation between Vp and carotid intima media thickness (r=-0.37; p<0.001).
      CONCLUSIONS: The aortic flow propagation velocity is a simple, feasible and
      reproducible marker of atherosoclerosis with an acceptable sensitivity and
      specificity. There is a need for longitudinal prospective studies to use it
      routinely.

PMID- 22634908
TI  - Does epidural clonidine improve postoperative analgesia in major vascular
      surgery?
AB  - AIM: To determine the quality and duration of the analgesic and haemodynamic
      effects of clonidine when used as an additional analgesic for postoperative
      epidural analgesia in major vascular surgery. METHODS: The prospective, single
      blinded study involved 60 patients randomised into three groups (20 patients
      each): Group BM- bupivacaine 0.125% and morphine 0.1 mg/ml; Group BC-bupivacaine
      0.125% and clonidine 5 MUg/ml; Group MC-morphine 0.1 mg/ml and clonidine 5 MUg/ml
      continuously infused at 5 ml/h. The quality and duration of the analgesia
      measured by the Visual Analogue Scale (VAS) at rest and on movement, additional
      analgesia requirements, sedation scores, haemodynamic parameters and side effects
      (respiratory depression, motor block, toxic effects, nausea and pruritus) were
      recorded. RESULTS: The average VAS scores at rest and on movement were
      significantly lower in Group MC at two, six and 24 hours following the start of
      epidural infusion (P<0.05). The duration of the analgesic effect after finishing
      the epidural infusion was significantly longer in Group MC (P<0.05). Patients
      from Group MC were intubated longer. Additional analgesia consumption, sedation
      scores and haemodynamic profiles were similar in all three groups. Pruritus was
      more frequent in morphine groups (P<0.05), but other side effects were similar in
      all three groups. CONCLUSIONS: Under study conditions, clonidine added to
      morphine, not 0.125% bupivacaine, provided significantly better pain scores at
      two, six and 24 hours following the start of epidural infusion and the longest
      lasting analgesia following the discontinuation of epidural infusion. However,
      patients from the Group MC were mechanically ventilated longer than patients from
      other two groups. Continuous monitoring of the patient is necessary after the
      administration of clonidine for epidural analgesia.

PMID- 22634909
TI  - Surgical treatment of patients with penetrating chest injuries sustained in war.
AB  - AIM: To show our experience in treatment of patients with penetrating chest
      injuries sustained during the Homeland War in Croatia METHODS: It was a
      retrospective study based on the records of the Department of Surgery of the
      University Hospital of Osijek (Croatia). All patients surgically treated during
      the wartime period (1991.-1995.) were analysed with respect to death rate, causes
      of injuries, frequency of injuries of thoracic organs and frequency of combined
      injuries of thorax and abdomen. Most of our patients were treated with
      thoracotomy as opposed to the common protocol (thoracostomy) applied in usual
      treatments. RESULTS: The study includes 157 patients with penetrating chest
      wounds, 111 (70.7%) of which were from metal fragments of bursting artillery, 37
      (23.6%) of the wounded were exposed to gunshot bullets, and 9 (5.7%) had stab
      injuries. Lung injuries had 134 (85.4%) patients, and 15 (9.6%) had injuries of
      the heart. Chest injuries combined with injuries of abdominal organs happened in
      30 (19%) cases. The abdominal organs in question were the liver, spleen, stomach,
      and colon, in eight (26.6%), seven (23.3%), four (13.3%), and three (10.0%)
      cases, respectively. Thoracotomy was performed in 144 (91.7%) cases, 13 (8.3%) of
      the patients underwent thoracostomy, and 134 (85.3%) patients stayed alive.
      CONCLUSIONS: It points out that, in our case due to organizational problems,
      aggressive surgical procedure of patients with penetrating chest and multiple
      injuries sustained in war was the good choice.

PMID- 22634910
TI  - Exploring possibilities in nasal polyposis treatment at one Croatian hospital.
AB  - AIM: To validate different operative techniques commonly used for nasal polyposis
      (NP) treatment. METHODS: This is a retrospective study exploring data on the NP
      surgery during a five-year period at the Ear, Nose and Throat Department at
      Clinical Hospital Centre Osijek, Croatia. Data were analysed regarding patients'
      gender, age, type of the surgery performed, and possible recurrence. Recurrence
      rate among patients that were followed up during that period of time and operated
      by different techniques (FESS vs. classical polipectomy) was compared. RESULTS:
      Most frequently used operative technique was classical bilateral polypectomy, in
      62.9% (154/245) of cases. The frequency of classical polypectomy was
      significantly decreased from 42/46 (91.3%) in 2006 to 34/60 (56.7%) cases in
      2010, whereas the frequency of FESS in combination with classical polypectomy was
      significantly increased during that period (p<0.0001). Among patients with
      relapse that were followed up most of them were subjected to classical
      polypectomy at the time of their first surgery (9/10), thus implicating higher
      incidence of relapse in classically polypectomized patients. CONCLUSIONS: A
      higher incidence of recurrence in patients who underwent classical polypectomy
      implicates the need for additional precautions when choosing an operative
      technique. In addition, further investigation of NP and better understanding of
      etiology as well as the development of more specific drugs would be of great
      importance for the improvement of nasal polyposis treatment in the future.

PMID- 22634911
TI  - The efficacy of novel therapeutic modalities of isolated ocular vasculitis vs
      ocular vasculitis as a systemic disease.
AB  - AIM: To evaluate the efficacy of new therapeutic modalities with the observation
      period of three years on patients with isolated ocular vasculitis in comparison
      with ocular vasculitis as a systemic disease. METHODS: The effectiveness of the
      therapy was assessed based on the changes in visual acuity and degree of ocular
      inflammation (mild, medium, moderate, severe) with the following parameters:
      vitreous body cloudiness, blood vessels layering, macula oedema, blood vessels
      occlusion and new vascularisation RESULTS: New therapeutic modalities resulted in
      reduction in the number of patients with severe inflammation in the group of
      isolated ocular vasculitis from 8(13.5%) to 7(12.2%) after three years, while the
      number of patients with mild inflammation increased from 13(20.7%) to 18 (29.3%)
      in the same group (p>0.05). The number of patients with severe ocular
      inflammation in a group of ocular vasculitis as systemic disease increased from
      3(16.2%) to 4(21.6%), because of the presence of patients with Behcet's disease.
      The number of patients with visual acuity less than 0.1 decreased from 11(17%) to
      8(13.4%) in a group of patients with ocular vasculitis as systemic disease, which
      was associated with the presence of Behcet's disease too (p>0.05). CONCLUSIONS:
      Although the effect of new therapeutic modalities did not result in statistically
      significant improvement in visual acuity and reducing inflammation, systemic and
      intravitreal corticosteroids with steroid-sparing immunomodulatory therapy
      represents effective strategies in forms of isolated ocular vasculitis and ocular
      vasculitis as systemic disease.

PMID- 22634912
TI  - First sexual intercourse (sexarche) in youth in Bosnia and Herzegovina.
AB  - AIM: To determine the average age of sexarche in young people in the territory of
      Bosnia and Herzegovina (BandH) in relation to their sex, place and life-style and
      religion. METHODS: A survey (anonymous questionnaire) about sexual behavior of
      young people in the period 2007-2009 on the sample of 6000 individuals
      (experimental group of 5000 students and control group of 1000 non-students) has
      been conducted in four major university cities in BandH: Sarajevo, Tuzla, Mostar,
      Banja Luka. RESULTS: A total of 3.659 (out of 6000, 61%) sexually active youth of
      which 1871 (51.1%) males, and 1788 (48.9%) females were observed. Among student
      population there were 3001 (82%), and among non-students 658 (18%) sexually
      active individuals. The mean (average) age of sexarche in sexually active youth
      as a whole was 17.34 (SD +/- 1.77) in males and 18.20 (SD +/- 1.84) in females
      (p<0.001), and among students and non-students, 17.72 (SD +/- 1.81), and 17.92
      (SD +/- 2.04) (p=0.02), respectively (p=0.01). There was a significant difference
      of the average values of sexarche among members of different religions, in males
      ( p<0.001) as well as in females (p=0.004) in both groups. CONCLUSIONS: Results
      of this study do not present a descending trend of the average age of first
      coitus in youth in BiH, which is contrary to the results of other countries.

PMID- 22634913
TI  - Epidemiological, clinical and pathological characteristics of colorectal cancer
      in patients treated at the Clinical Center of Tuzla University.
AB  - AIM: To investigate hospital morbidity and incidence of colorectal cancer (CRC)
      in the Tuzla Canton between 2000 and 2004, as well as mortality incidence and
      degree of disease progression. METHODS: A total of 383 patients were enrolled in
      this study, all of them with CRC. Pathohistological analyses were performed in
      all patients after colonoscopy. Afterwards, the patients underwent surgery and
      obtained material was also pathohistologically analyzed in order to perform the
      Astler-Coller classification and the classification of the location of CRC.
      RESULTS: In the period 2000-2004 in the Tuzla Canton there were 383 newly
      diagnosed patients with CRC. The average age of the patients was 62 +/- 12 years,
      and the incidence was equally distributed per genders. Rectal tumour was noted in
      145 (37.9%) patients, and in 238 (62.1%) tumor was found elsewhere in the colon.
      Average incidence of the CRC was 15.73/100,000, with a dramatic increase in
      incidence in 2003 of 27.40/100,000. The average mortality incidence during the
      study was 6.89/100,000, and the largest number of the patients (339, 88.6%) was
      in an advanced stage of the disease. CONCLUSIONS: There has been a significant
      increase in the number of newly detected cases of CRC in the Tuzla Canton during
      2000- 2004, which implies the need for initiating a National Early CRC Detection
      Programme.

PMID- 22634914
TI  - Obesity and related factors in 7-12 year-old elementary school students during
      2009-2010 in Sari, Iran.
AB  - AIM: To define the prevalence of obesity and its related factors in 2-7 year-old
      elementary school students in Sari city (Mazandaran, Iran). METHODS: In this
      descriptive cross sectional study, which was conducted in the 2009-2010 period,
      the study population included 7-12 year-old first to fifth grade elementary
      school students in Sari. Sampling was multi-stage and stratified randomization at
      level of the target students. Student's height and weight were measured using
      stediometer and digital scales. Body Mass Index (BMI) was calculated. A
      questionnaire about feeding habits and socio-economic status(SES) of families was
      used. Data collection was performed using phone interview with parents also the
      questionnaire's records. Analysis was done in SPSS16 using appropriate
      statistical tests, p<0.05 was considered as significant. RESULTS: Of 653
      students, 297 (45.5%) were male, 177 (27.4%) children were overweight (BMI>85%)
      and 78 (12% ) were obese (BMI> 95%). Higher prevalence of obesity in the children
      with good socio economic status was found (p=0.001). Significant relationship
      between usage of fast food and obesity, and between school grade and obesity (p=
      0.001) was found. CONCLUSIONS: The overall prevalence of obesity in studied
      children was high, which suggests the need for serious attention in the health
      system, extensive studies, also designing and implementation of interventions
      with regard to childhood obesity.

PMID- 22634915
TI  - Chemometric analysis of groundwater quality data around municipal landfill and
      paper factory and their potential influence on population's health.
AB  - AIM: To assess the level of 15 groundwater quality parameters in groundwater
      samples collected around municipal landfill and paper factory in order to
      evaluate usefulness of the groundwater and its possible implication on the human
      health. METHODS: Obtained data have been analyzed by principal component analysis
      (PCA) technique, in order to differentiate the groundwater samples on the basis
      of their compositional differences and origin. RESULTS: Wastes and effluents from
      municipal landfill did not contribute significantly to the pollution of the
      aquatic medium. Groundwater degradation caused by high contents of nitrate,
      mineral oils, organic and inorganic matters was particularly expressed in the
      narrow area of the city centre, near the paper factory and most likely it has
      occurred over a long period of time. The results have shown that the
      concentrations of the most measured parameters (NO3-N, NH4-N, oils, organic
      matter, Fe, Pb, Ni and Cr) were above allowed limits for drinking and domestic
      purposes. CONCLUSIONS: This study has provided important information on
      ecological status of the groundwater systems and for identification of
      groundwater quality parameters with concentrations above allowable limits for
      human consumption. The results generally revealed that groundwater assessed in
      this study mainly does not satisfy safe limits for drinking water and domestic
      use. As a consequence, contaminated groundwater becomes a large hygienic and
      toxicological problem, since it considerably impedes groundwater utilization.
      Even though, all of these contaminants have not yet reached toxic levels, they
      still represent long term risk for health of the population.

PMID- 22634916
TI  - Soil chemicals properties and wheat genotype impact on micronutrient and toxic
      elements content in wheat integral flour.
AB  - AIM: To determine impact of soil chemical properties and different wheat
      genotypes in Croatia on micronutrient and toxic elements content in wheat
      integral flour. METHODS: Research was conducted and soil samples were collected
      from two different production areas in the Republic of Croatia: Ovcara and Dalj.
      Besides soil samples, grain samples of four different Croatian wheat genotypes
      were also collected and analyzed. In total, 40 samples of soil and 40 samples of
      wheat grain were analysed for total (aqua regia) and plant available (EDTA
      extraction) heavy metal content of Fe, Mn, Zn, Cu, Pb, Cd RESULTS: Determined
      soil pHKCl ranged from 5.63 to 6.25 at Ovcara and from 6.95 to 7.37 at Dalj
      sampling sites. The highest total concentration of heavy metals in soil were
      determined for Fe, followed by Mn, Zn, Cu, Pb and the lowest total concentration
      was recorded for Cd. The highest EDTA concentrations in soil were determined for
      Mn, than followed by Fe, Cu, Pb, and the lowest EDTA concentration was recorded
      for Cd. The highest concentration in integral wheat flour was found for Fe, than
      lower for Mn, Zn, Cu, Pb and the lowest concentration was found for Cd. If
      consumers in Croatia used daily 203 g of bread made of integral flour, they would
      take 2.31 to 8.44 MUg Cd daily, depending on soil and wheat genotype.
      CONCLUSIONS: The analysed soil and winter wheat genotypes have significant impact
      on potential daily intake of toxic and essential heavy metals by integral flour
      or bread.

PMID- 22634917
TI  - Risk factors and diabetic retinopathy.
AB  - The aim of the study was to determine the correlation between risk factors and
      diabetic retinopathy, which is the leading cause of blindness in developed
      countries for patients aged 20 to 65. We compared risk factors between patients
      without retinopathy, with non-proliferate and with proliferate retinopathy
      (p<0.05). Duration of diabetes is most important for the development of
      retinopathy. Hyperglycaemia and high blood pressure are important for
      progression. Better control of blood sugar and elevated blood pressure can reduce
      progression of retinopathy and risk of vision loss.

PMID- 22634918
TI  - Cyclocryotherapy in neovascular glaucoma treatment.
AB  - The main goal in the struggle with neovascular glaucoma is to control intraocular
      pressure (IOP) and pain. 152 patients, e.g., 203 eyes, were examined at the
      Clinic of Ophthalmology, Clinical Centre of Kragujevac, Serbia, in period between
      01. 01. 2005 - 31. 12. 2010. Cyclocryoanemisatio was performed for all patients.
      Measurments of IOP showed statistical significant changes before and after the
      treatment for every patients. There was no difference in sex distribution, but a
      difference was noted in age distribution. Early posttreatment complications
      included hyphema, fibrin's exudation, chemosis. Cyclocryotherapy is usefull and
      accessible method for control of intensive pain in neovascular glaucoma.

PMID- 22634919
TI  - Increasing incidence of rubella in Republika Srpska in the period 2006-2010.
AB  - The aim of this study was to investigate the incidence rate of rubella in
      Republika Srpska in the period between 2006 and 2010. The total number of 1236
      cases of rubella was reported during the reporting period with manifold
      increasing incidence from 0.5 in 2006 to 54.7 in 2010 per 100,000 habitants. In
      the last two years of observation there was a disease outbreak in Republika
      Srpska. Inadequate immunization, migration and lack of funds caused a reduction
      in the overall level of public health and health system which led to a drastic
      increase in the number of rubella cases.

PMID- 22634920
TI  - Six years of following up a glomus jugulare tumor - a case report.
AB  - This case report followed up a patient for six years after she had been
      successfully treated by embolization and gamma knife surgery, while a complete
      surgical resection was contraindicated because of the high risk of possible
      mortality outcome. A development of internal hydrocephalus in a subacute
      postoperative period as a probable postoperative complication related to gamma
      knife surgery was noted.

PMID- 22634921
TI  - Atrial myxoma as a cause of stroke: emboli detection and thrombolytic treatment.
AB  - It presents a case of a 42-year-old female patient who was admitted to the stroke
      unit for right-sided hemiplegia and global aphasia, without conventional stroke
      risk factors. As the patient presented within the therapeutic time window and had
      no contraindications for thrombolysis, intravenous thrombolytic treatment was
      initiated. Brain CT showed multiple hypodense partly confluent lesions in the
      territory of the left middle cerebral artery. For the purpose of determining the
      etiology of the stroke, TCD was performed and after cerebral microemboli were
      detected, transthoracic echocardiography was indicated, the finding of which
      showed the presence of a myxoma in the left atrium. The patient underwent surgery
      and thereafter her neurological deficits improved.

PMID- 22634922
TI  - Three-dimensional transvaginal ultrasonographic view of intact cornual pregnancy.
AB  - This work presents the case of the cornual ectopic pregnancy of a twenty year old
      patient who came to be examined due to amenorrhea which had lasted for seven
      weeks. Two-dimensional transvaginal ultrasound uncovered the existence of an
      intact ectopic pregnancy. Use of three-dimensional transvaginal ultrasound in a
      coronal section confirmed the diagnosis of cornual ectopic pregnancy, and the
      patient underwent laparatomy. Given that three-dimensional ultrasound enables
      excellent anatomical orientation and precise localization of pathological
      findings, especially in the coronal plane of the uterus, it can be expected that
      this technological advance can improve accuracy in diagnosis of cornual ectopic
      pregnancy.

PMID- 22634923
TI  - Intermittent hepatic porphyria in pregnancy with good perinatal outcome.
AB  - Porphyrias are rare metabolic diseases caused by enzymatic defects of the haeme
      biosynthesis. Association of pregnancy and acute porphyria is rare, but mortality
      rate among pregnant women from acute attack has been reported up to 42%. This
      paper presents a patient with pregnancy complicated by intermittent hepatic
      porphyria with good perinatal outcome. The pattern of the attack in pregnancy
      varies individually and it makes porphyric pregnancies a challenge. Previously
      diagnosed porphyria patients should be closely monitored during pregnancy and
      diagnosis of acute porphyria must be also considered in all pregnant women with
      unexplained abdominal pain.

PMID- 22634924
TI  - Traumatic anterior dislocation of the crystalline lens and its surgical
      management.
AB  - This paper reports a case of a 57-year old female who had sustained a blunt
      ocular trauma resulting in anterior dislocation of the crystalline lens and acute
      painful visual loss in the left eye. The patient was managed with anterior
      chamber intracapsular phacoemulsification through a small anterior capsulotomy,
      pars plana vitrectomy, and surgical iridotomy. Aphakia was corrected by a contact
      lens. Two months after the surgery, the best corrected visual acuity was 0.9 in
      the left eye. The vision and retina remained stable in her follow-up examination
      1 year later. Anterior dislocation of the crystalline lens can cause severe
      complications so that dislocated lens should be removed immediately.

PMID- 22634925
TI  - Acute paroxysmal praecordial pain as a somatosensory elementary partial onset of
      epileptic seizure.
AB  - It presents a 60-year-old female patient with acute paroxysmal intensive pain
      attacks in the praecordial area that spread to the left hand and were associated
      with mild transient left hemiparesis, progressing to a myoclonic focal seizure in
      the region of left abdomen. The diagnostic procedure was interrupted several
      times by intensive pain attacks, but excluded acute thoracic pathological
      process, whilst a brain scan found a large, partially necrotic tumour with
      incipient bleeding and severe oedema subcortically in the right parietal lobe. We
      are describing a clinical presentation of symptomatic, simple focal,
      somatosensory epileptic seizure with dominance of intensive pain that progress in
      myoclonic, somatomotor focal seizure and Todd's Palsy as the first sign of
      glioblastoma bleeding.

PMID- 22634926
TI  - Lumboischialgia as the first sign of stomach cancer.
AB  - The paper reports on a case of a seventy-three-year-old male patient, whose
      disease was initially manifested by severe low back pain and lumboischialgia of
      the right leg as the first and only, and later, the leading symptom of
      disseminated adenocarcinoma of the stomach. The unusual presentation of stomach
      cancer confirms the necessity of simultaneous treatment of pain and determination
      of its etiology. It also indicates the need for re-evaluation of diagnosis when
      there is no favorable clinical effect of applied therapy.

PMID- 22634927
TI  - Benign blue naevus of the lungs.
AB  - Blue naevus is a dark blue, gray or black lesion consisted of dermal melanocytes
      and usually found on face, scalp, or on the dorsum of hands and feet. Two well
      defined histologic and clinical variants, designated as "common" and "cellular",
      have been recognised. An unusual case of accidentally detected common blue naevus
      of the lungs has been reported. The specimen of lung tissue was taken during
      autopsy of a 62-year old woman who died of myocardial infarction. Microscopic
      analysis revealed the area containing melanocytes filled with melanin pigment.

PMID- 22634928
TI  - History and factors of survival of total hip arthroplasty.
AB  - Since the 1960s total hip arthroplasty (THA) has represented one of the greatest
      accomplishments in orthopedic surgery. It improves the functionality, working
      ability and quality of life of patients with non-functional hip joint due to
      various reasons. This article reviews general and regional history of THA,
      current knowledge and concepts regarding the long-term outcomes of the procedure
      and emphasizes the need for establishing national (and international) THA
      registries as an essential way of gathering data critical for decision making in
      daily practice as well as in defining national healthcare policies in respect to
      arthroplasty procedures.

PMID- 22634929
TI  - Anesthesia for hip replacement surgery.
AB  - Hip replacement surgery is a common and effective procedure for the relief of
      pain and loss of function. The number of procedures is increasing and great
      interest is shown for the manner of outcome improvement following hip replacement
      surgery. Last decade (2001-2010) is declared as the Bone and Joint Decade and has
      been characterized by many innovations in hip replacement surgery including
      minimally invasive technique but also by improvements in anesthetic technique.
      However there is no consensus about most appropriate anesthetic and analgesic
      techniques to use. Total hip replacement is procedure characterized by great
      perioperative disturbances including cardiovascular complications, high incidence
      of thromboembolic complications, possible significant perioperative blood loss,
      possible bone cement effect and high level of postoperative pain. Anesthetic
      assessment of patients include preoperative preparations, intraoperative and
      postoperative care. Most important factors determining outcome of patients
      include preoperative assessment and planning in order to minimize potential
      anesthetic problems, optimize co-morbidity and provide the most appropriate
      anesthetic for the patient. In this article all problems of preoperative
      assessment are discussed. The recent data of advantages of regional anesthetic
      technique are outlined. All the problems of intraoperative course and how to
      avoid them are presented. The possible techniques of postoperative pain therapy
      are also presented. The importance of thromboprophylaxis is outlined and recent
      guidelines for thromboprophylaxis are given including recommendations for new
      antithrombotic drugs. Our recommendation is to always prepare a patient for this
      procedure, analyse preoperative status, choose optimal anesthetic technique,
      provide thromboprophylaxis and multimodal pain therapy according to accepted
      guidelines.

PMID- 22634930
TI  - Minimally invasive hip arthroplasty: advantages and disadvantages.
AB  - BACKGROUND: To present the method and advantages of anterior minimally invasive
      surgery (AMIS) in coxarthrosis and hip fractures treatment. METHODS: During 2008
      and 2009, 35 patients were treated with AMIS method. They were compared with 35
      patients treated with lateral, transgluteal approach (control group) in the same
      period. All operations were performed by the same surgical team. The main reason
      for surgery was hip arthrosis, only two patients in AMIS group underwent surgery
      because of femoral neck fracture. Early postoperative complications and
      functional status are followed by Haris Hip Score (HHS). RESULTS: Operation time
      was shorter and postoperative blood loss was lesser in AMIS group (78 min, 490
      ml) than in the control group (85 min, 570 ml). In the AMIS group one patient had
      each post-operative knee pain, fractured tip of a large trochanter, acetabular
      overreaming, perforation of shaft with rasp, and two patients had parestesis
      n.cutaneus femoris lat. They had no infections or hip luxation. In the control
      group early hip luxation and superficial wound infections have occurred in one
      and two cases, respectively. Patients in the AMIS group were more satisfied,
      demanded less analgesics and their rehabilitation was faster. Haris Hip Score in
      the AMIS group after 2 months was 80 compared with 69 in the controls, and after
      4 months 92 compared to 88 in controls. CONCLUSIONS: AMIS is a safe, reproducible
      and rewarding technique which provides low morbidity and fast postoperative
      recovery for the patient.

PMID- 22634931
TI  - Diagnosis and treatment of peri-prosthetic infections in total hip replacement.
AB  - Total hip replacement (THR) has a very good clinical outcome. Peri-prosthetic
      infection is a severe complication with infection rates 0.5-2% after primary THR.
      Systematic reviews and meta-analyses published in recent years have allowed
      drafting of evidence based guidelines for diagnosis and treatment of peri
      prosthetic infection after THR. If an implant related infection is suspected, a
      complex standardised procedure should be carried out. The most commonly cultured
      microorganisms causing peri-prosthetic infections are coagulase-negative
      staphylococci and S.aureus followed by mixed flora, streptococci, gram-negative
      bacilli, enterococci and anaerobes. Different treatment strategies can be applied
      regarding virulence of a specific pathogen, mechanical stability of the implant
      and patient's condition. Treatment options always include antibiotic therapy
      with/without surgical procedures like debridement, one/two stage approach or
      resection arthroplasty.

PMID- 22634932
TI  - Retrospective study of total hip arthroplasty in Brod-Posavina and Pozega-
      Slavonia counties in 2010.
AB  - The aim of this retrospective study is to present the incidence of total hip
      arthroplasty (THA) in Brod-Posavina and Pozega-Slavonia counties in 2010 along
      with an analysis of post-operative complications. The research was carried out at
      orthopaedic departments in three hospital institutions, "Dr. Josip Bencevic
      "Slavonski Brod General Hospital, the Nova Gradiska General Hospital and the
      Pozega General County Hospital. A total of 27 849 patients was examined in
      orthopedic outpatient clinics, 1 457 surgical procedures were conducted, of which
      239 (16.40%) were THA. There were five (2.09%) dislocations of endoprosthesis,
      one case (0.42%) of endoprostheses infection, whereas none of periprosthetic
      fractures and peroneal nerve palsy were presented.

PMID- 22634933
TI  - Total hip arthroplasty in avascular necrosis of the femoral head in a patient
      with transplanted heart.
AB  - With the improvement of transplantation techniques and immunosupresive treatment
      of transplanted patients, the number of heart transplantations increases
      worldwide including Croatia. The survival of such patients is significantly
      increased. Therefore, the prevalence of known complications is high, one of which
      is avascular necrosis of the femoral head. This paper presents a case of the
      first patient in Croatia who underwent bilateral hip arthroplasty due to
      bilateral avascular necrosis of the femoral head as a side effect of
      corticosteroid therapy after heart transplantation.

PMID- 22634934
TI  - Use of multislice computed tomography in radiological treatment of patients with
      hip pathology.
AB  - In this paper we are presenting the application of Multislice CT Scan (MSCT) as a
      part of radiological treatment in a female patient with avascular necrosis of
      head and neck of the right femur, which occurred as a consequence of
      developmental hip dysplasia. The left hip joint of the patient was previously
      replaced by a prosthetic implant.

PMID- 22634935
TI  - Olive oil biophenols and women's health.
AB  - Olea europea, the olive tree, is an ancient tree that originates from the
      Mediterranean environment of Asia Minor. The edible olive fruit is also used for
      its oil, gained by the process of pressing, a nutrient with proven beneficial
      effects. Virgin olive oil is the natural juice of the olive fruit, which plays a
      major role in the healthy Mediterranean diet. The source of its health effects
      are the biophenols and squalenes (oleocanthal, tyrosol, hydroxytyrosol,
      oleuropein) it contains. They provide an exceptional antioxidative activity,
      removing harmful compounds from the body. Oxidants are essential in the genesis
      of many diseases and conditions, such as cardiovascular disorders, cancer,
      osteoporosis, Alzheimer disease, and premenstrual syndrome. Oleic acid, an
      unsaturated fatty acid, has demonstrated a significant effect in the prevention
      of malignant diseases such as colon cancer and breast cancer. Biophenols from
      olive oil successfully suppress the synthesis of LDL, a protein that is crucial
      in the development of cardiovascular disease, by reducing blood pressure and the
      development of atherosclerotic plaques. In addition, there is strong evidence of
      the antimicrobic effect of the biphenols from olive oil that successfully destroy
      colonies of microorganisms which may cause respiratory tract, intestinal, and
      genital tract infections.

PMID- 22634936
TI  - Monophyly, divergence times, and evolution of host plant use inferred from a
      revised phylogeny of the Drosophila repleta species group.
AB  - We present a revised molecular phylogeny of the Drosophila repleta group
      including 62 repleta group taxa and nine outgroup species based on four
      mitochondrial and six nuclear DNA sequence fragments. With ca. 100 species
      endemic to the New World, the repleta species group represents one of the major
      species radiations in the genus Drosophila. Most repleta group species are
      associated with cacti in arid or semiarid regions. Contrary to previous results,
      maximum likelihood and Bayesian phylogenies of the 10-gene dataset strongly
      support the monophyly of the repleta group. Several previously described
      subdivisions in the group were also recovered, despite poorly resolved
      relationships between these clades. Divergence time estimates suggested that the
      repleta group split from its sister group about 21millionyears ago (Mya),
      although diversification of the crown group began ca. 16Mya. Character mapping of
      patterns of host plant use showed that flat leaf Opuntia use is common throughout
      the phylogeny and that shifts in host use from Opuntia to the more chemically
      complex columnar cacti occurred several times independently during the history of
      this group. Although some species retained the use of Opuntia after acquiring the
      use of columnar cacti, there were multiple, phylogenetically independent
      instances of columnar cactus specialization with loss of Opuntia as a host.
      Concordant with our proposed timing of host use shifts, these dates are
      consistent with the suggested times when the Opuntioideae originated in South
      America. We discuss the generally accepted South American origin of the repleta
      group.

PMID- 22634938
TI  - Oral mucosal color changes as a clinical biomarker for cancer detection.
AB  - Screening is a key tool for early cancer detection/prevention and potentially
      saves lives. Oral mucosal vascular aberrations and color changes have been
      reported in hereditary nonpolyposis colorectal cancer patients, possibly
      reflecting a subclinical extracellular matrix abnormality implicated in the
      general process of cancer development. Reasoning that physicochemical changes of
      a tissue should affect its optical properties, we investigated the diagnostic
      ability of oral mucosal color to identify patients with several types of cancer.
      A total of 67 patients with several histologically proven malignancies at
      different stages were enrolled along with a group of 60 healthy controls of
      comparable age and sex ratio. Oral mucosal color was measured in selected areas,
      and then univariate, cluster, and principal component analyses were carried out.
      Lower red and green and higher blue values were significantly associated with
      evidence of cancer (all P<0.0001), and efficiently discriminated patients from
      controls. The blue color coordinate showed significantly higher sensitivity and
      specificity (96.66+/-2.77 and 97.16+/-3.46%, respectively) compared with the red
      and green coordinates. Likewise, the second principal component coordinate of the
      red-green clusters discriminated patients from controls with 98.2% sensitivity
      and 95% specificity (cut-off criterion<=0.4547; P=0.0001). The scatterplots of
      the chrominances revealed the formation of two well separated clusters,
      separating cancer patients from controls with a 99.4% probability of correct
      classification. These findings highlight the ability of oral color to encode
      clinically relevant biophysical information. In the near future, this low-cost
      and noninvasive method may become a useful tool for early cancer detection.

PMID- 22634939
TI  - [Pay for performance in Colombian healthcare].
AB  - OBJECTIVE: Describing the extent and forms of use of pay for performance (P4P) in
      Colombian healthcare. METHODS: This was a descriptive study based on interviews
      and surveys of health insurance agency managers in Bogota, Colombia. The authors
      relied on transaction cost theory to interpret the results. RESULTS: P4P was
      found to be used by contribution scheme insurers in an outpatient setting,
      basically in promotion and prevention; P4P is not being used in a hospital
      setting. Subsidized scheme insurers do not use P4P. Similarly, P4P is not being
      used in the case of so called associated users. CONCLUSIONS: P4P use in Colombia
      is limited. Colombian practice only partially validates the transaction costs
      theory approach to governance model attributes, one of which is incentive
      intensity.

PMID- 22634940
TI  - [Case study: school meals' management in Santiago de Cali and Bogota].
AB  - OBJECTIVE: This research was aimed at ascertaining the state's role regarding
      hunger and how it manages to combat this matter; a food security program in two
      Colombian cities was thus assessed (i.e. school meals' provision in Cali and
      Bogota). METHODS: A qualitative approach was adopted; documentary analysis,
      participant observation and in-depth interviews with various actors for both
      selected cases were used as data collection techniques. RESULTS: It was found
      that several measures taken in this area were not covered by regulatory
      principles aimed at covering all the dimensions of food security. Serious
      weaknesses in school meals' management in Cali were associated with a weak
      environment regarding the fight against hunger. School meals' management in
      Bogota was aimed at recognizing the right to food as being supported by an
      institutional process where the issue of reducing hunger has become a firm
      purpose. DISCUSSION: School meals' program management was associated with the
      characteristics of its product, thereby affecting the program and the
      population's food and nutritional status; state management thus becomes another
      dimension of food security.

PMID- 22634941
TI  - [Physical activity and tobacco and alcohol use in a group of university
      students].
AB  - OBJECTIVE: Determining the prevalence of physical activity, smoking and drinking
      alcohol in a group of university students studying in the social-health sciences'
      area. METHODOLOGY: A shortened version of the International Physical Activity
      Questionnaire was used with a sample of 548 students from the social-health
      sciences area (431 females and 117 males, average 20 years old: 2.3 SD) and a
      survey about living habits for obtaining information related to drinking alcohol
      and smoking. The physical activity index, activity levels, percentage of smoking
      and drinking alcohol were all calculated. The Cramer's V coefficient was used for
      establishing an association between variables, the t-test for evaluating
      differences in physical activity regarding gender and the Brown Forsythe test
      concerning qualifications. RESULTS: 80 % of the students were classified as being
      regularly active. Significant differences were found between the Physical
      Activity Index, gender (p=0.0) and qualifications (p=0.038). Smoking prevalence
      was 33 % and drinking alcohol 58 %, no significant differences being found
      regarding gender. No significant associations were found between physical
      activity, smoking and drinking alcohol. CONCLUSIONS: A high percentage of
      students regularly took part in physical activity. However, some of them did not
      reach the minimum parameters for obtaining health-related benefits. The
      percentage of students consuming alcohol and smoking was high. Programs must be
      implemented for promoting healthy habits in university students, specifically
      aimed at optimizing taking part in sports and preventing and reducing smoking and
      drinking alcohol.

PMID- 22634942
TI  - [The level of knowledge concerning cardiovascular risk factors in people living
      in Naguanagua, Venezuela].
AB  - OBJECTIVE: Associating the level of awareness concerning cardiovascular risk
      factors related to changes in clinical, anthropometric and biochemical markers
      regarding cardiovascular risk in people living in Naguanagua, Venezuela. METHOD:
      205 patients aged 18 to 77 years were evaluated; weight, height, waist
      circumference, blood pressure, glucose and serum lipid profile were measured. A
      survey assessed the patients' level of awareness regarding cardiovascular risk
      factors. RESULTS: A high frequency of abdominal obesity (67 %), being overweight
      and obese (38 %) and suffering from hypertension (26 %) was observed. Nearly 60 %
      of respondents claimed to know about cardiovascular risk factors, but only 14.7 %
      of them recognized the eleven factors considered to define such level of
      knowledge. More than half of the participants showed a low level of awareness
      concerning cardiovascular risk factors; average levels of total cholesterol,
      cholesterol LDL and triglycerides were significantly lower in the group having a
      high level of knowledge concerning cardiovascular risk factors. CONCLUSIONS:
      Extremely low levels of awareness regarding cardiovascular risk factor prevalence
      and high frequency concerning changes in clinical, anthropometric and biochemical
      markers for cardiovascular risk were higher in the group having a high level of
      knowledge of cardiovascular risk factors, thereby confirming the need for
      implementing strategies for raising Venezuelan communities' level of knowledge
      regarding cardiovascular risk factors and also encouraging them to adopt a
      lifestyle associated with reduced cardiovascular risk factors and self-care.

PMID- 22634937
TI  - Reticulate evolution on a global scale: a nuclear phylogeny for New World
      Dryopteris (Dryopteridaceae).
AB  - Reticulate, or non-bifurcating, evolution is now recognized as an important
      phenomenon shaping the histories of many organisms. It appears to be particularly
      common in plants, especially in ferns, which have relatively few barriers to
      intra- and interspecific hybridization. Reticulate evolutionary patterns have
      been recognized in many fern groups, though very few have been studied rigorously
      using modern molecular phylogenetic techniques in order to determine the causes
      of the reticulate patterns. In the current study, we examine patterns of
      branching and reticulate evolution in the genus Dryopteris, the woodferns. The
      North American members of this group have long been recognized as a classic
      example of reticulate evolution in plants, and we extend analysis of the genus to
      all 30 species in the New World, as well as numerous taxa from other regions. We
      employ sequence data from the plastid and nuclear genomes and use maximum
      parsimony (MP), maximum likelihood (ML), Bayesian inference (BI), and divergence
      time analyses to explore the relationships of New World Dryopteris to other
      regions and to reconstruct the timing and events which may have led to taxa
      displaying reticulate rather than strictly branching histories. We find evidence
      for reticulation among both the North and Central/South American groups of
      species, and our data support a classic hypothesis for reticulate evolution via
      allopolyploid speciation in the North America taxa, including an extinct diploid
      progenitor in this group. In the Central and South American species, we find
      evidence of extensive reticulation involving unknown ancestors from Asia, and we
      reject deep coalescent processes such as incomplete lineage sorting in favor of
      more recent intercontinental hybridization and chloroplast capture as an
      explanation for the origin of the Latin American reticulate taxa.

PMID- 22634943
TI  - [The dynamics of HIV-AIDS in Cali].
AB  - The classical Kermack-Mckendric SIR model for infectious disease transmission was
      used for studying the dynamics of HIV-AIDS in the city of Cali; individuals were
      classified as being susceptible, infected or recovered (SIR) on the assumption
      that sexual transmission would be the only means of transmission and that
      individuals would not recover or die. The model's parameters and basic
      reproductive numbers were estimated using information supplied by the Santiago de
      Cali Municipal Secretariat of Health, the Colombian Statistics Bureau (DANE) and
      the Municipal Planning department. Some scenarios were simulated to establish
      long-term disease trends. The system's equilibrium points were estimated and
      stability conditions analyzed finding that the current system had two equilibrium
      points: unstable, disease-free (E1) and stable, endemically asymptotic (E2).
      Taking information from 2008 as initial conditions, it was observed that the
      disease would tend towards equilibrium after a 100 year endemic. Simulations
      suggested that the disease would tend towards endemic equilibrium more slowly by
      reducing the probability of contact between susceptible and infected individuals
      and that the maximum number of infected and recovered could also become reduced.

PMID- 22634944
TI  - [Secondary students' knowledge about HIV-AIDS (Cartagena, Colombia)].
AB  - OBJECTIVE: Determining the level of HIV/AIDS knowledge amongst high-students
      living in Cartagena, Colombia. METHOD: A cross-sectional study was designed using
      a sample of secondary school students who completed a six-question questionnaire
      about their knowledge of HIV/AIDS and the myths related to it. Logistic
      regression was used for adjusting associations. RESULTS: A total of 2,625 10- to
      20-year-old students participated in the research. A group of 249 (9.5 OR; 8.4
      10.6 95 %CI) answered the questionnaire properly. Being a high-school student
      (2.62 OR; 4.82-13.29 95 %CI) and studying in a private school (1.32 OR, 1.24 to
      3.54 95 %CI), adjusted for age, were associated with having good HIV/AIDS
      knowledge. CONCLUSIONS: Students from secondary schools in Cartagena were seen to
      have limited knowledge of HIV/AIDS. A higher level of knowledge was observed
      amongst high school and private school students. More research is needed to
      strengthen sexual and reproductive health education.

PMID- 22634945
TI  - [The status of the dengue surveillance system in a Colombian municipality].
AB  - OBJECTIVE: The surveillance of dengue cases is essential for defining,
      implementing and assessing interventions and promptly detecting outbreaks.
      Municipal health authorities are the key stakeholders guaranteeing surveillance
      system quality and coverage and are the first users of the information so
      collected. The present study was aimed at assessing how well the dengue case
      surveillance system was operating in a municipality in the Valle del Cauca
      department of Colombia during 2008. METHODS: The CDC proposed model was used.
      Emphasis was placed on describing system operation, the available resources,
      compliance with reports and case adjustment and using information. Interviews
      were held with health workers. Dengue surveillance system data from the
      municipality, departmental health authorities and the Valle del Cauca Public
      Health Laboratory were reviewed. RESULTS: Notification coverage was 91.3 %. A
      lack of using surveillance software and delays in notification were identified.
      Three people were in charge of all public health responsibilities and none of
      them had had any training or prior knowledge regarding public health surveillance
      protocols. There had not been any systematic data analysis. CONCLUSIONS: As in
      other areas of Colombia, the lack of training, professional profile and other
      resources as well as a high turnover of public health personnel were the weakest
      points of the surveillance system in the municipality. Corrective measures for
      improving the surveillance system have now been implemented in the municipality
      which was studied.

PMID- 22634946
TI  - [Lipid profile frequency and relevancy as an initial test for peripheral
      vertigo].
AB  - OBJECTIVE: Determining the prevalence of requesting lipid profile as a first-line
      diagnostic method in patients having a clinical impression of peripheral vertigo
      and also determining such request's cost- benefit ratio. METHODS: This was a
      retrospective cross-sectional study of 201 clinical charts regarding patients
      diagnosed as having peripheral vertigo at the Teleton teaching hospital's
      outpatient services in Chia between January 2005 and July 2008. Clinical charts
      drawn up by both general practitioners and medical specialists at first-time
      visit were compiled and analyzed. RESULTS: The patients were aged 6 to 87 years
      old; 36 % were males and 64 % females. Lipid profile was requested for 76 % of
      the patients as initial diagnostic method; it was found that 80 % of the results
      revealed no abnormality. CONCLUSION: Although a high prevalence regarding a
      request for lipid profile first-line study was found for patients having
      peripheral vertigo, there was no scientific evidence supporting such requirement.
      Ordering this kind of study not only increases unnecessary costs concerning
      diagnostic methods but also involves unjustified treatment. Feedback is needed
      for both doctors and first attention staff to ensure that this type of practice
      becomes changed.

PMID- 22634947
TI  - Cost-effectiveness analysis regarding postoperative administration of vitamin-D
      and calcium after thyroidectomy to prevent hypocalcaemia.
AB  - OBJECTIVE: Hypocalcaemia is a frequently arising complication following total
      thyroidectomy. Routine postoperative prophylactic administration of vitamin D or
      metabolites and calcium reduce the incidence of symptomatic hypocalcaemia; this
      article reports evaluating its cost-effectiveness in Colombia. METHODS: Meta
      analysis was used for comparing the administration of vitamin D or metabolites to
      oral calcium or no treatment at all in patients following total thyroidectomy and
      a cost-effectiveness analysis was designed based on a decision-tree model with
      local costs. RESULTS: The OR value for the comparison between calcitriol and
      calcium compared to no treatment and to exclusive calcium treatment groups was
      0.32 (0.13-0.79 95 %CI) and 0.31 (0.14-0.70 95 %CI), respectively. The most cost
      effective strategy was vitamin D or metabolites and calcium administration,
      having a US $0.05 incremental cost-effectiveness ratio. CONCLUSION: Prophylactic
      treatment of hypocalcaemia with vitamin D or metabolites + calcium or calcium
      alone is a cost-effective strategy.

PMID- 22634948
TI  - [Leptospiral antibodies in a Colombian zoo's neotropical primates and workers].
AB  - OBJECTIVE: Detecting antibodies against Leptospira spp. in Neotropical primates
      and workers in a Colombian Zoo and identifying the risk factors associated with
      the disease. METHODS: A cross-sectional study was performed regarding 65
      Neotropical primates and 20 zookeepers. The samples were processed by
      microagglutination test (MAT) using a reference strain collection consisting of
      21 Leptospira serovars. The people being evaluated were given a structured survey
      to identify risk factors. RESULTS: There was 25 % (5/20) Leptospira spp.
      infection seroprevalence in the staff and 23.07 % (15/65) in Neotropical monkeys.
      The most frequently occurring serovars in workers were bataviae, gryppotyphosa
      and ranarum; icterohaemorrhagiae, pomona and ranarum were the predominant
      serovars in non-human primates. The black spider monkey (Ateles fusciceps), white
      fronted capuchin (Cebus albifrons) and white-footed tamarin (Saguinus leucopus)
      showed the highest reactivity. Most of the personnel were using protective
      clothing. CONCLUSIONS: The contact between primates and zookeepers involving
      different Leptospira sp. serovars was evident. Zoo personnel using protective
      clothing and their length of experience were considered to be protective factors
      for the disease. There may be a risk of Leptospira transmission between zoo
      animals and staff, and it is therefore important to strengthen active
      surveillance and implement promotion and prevention programs.

PMID- 22634949
TI  - Nasal carriage of Panton Valentine leukocidin-positive methicillin-resistant
      Staphylococcus aureus in healthy preschool children.
AB  - OBJECTIVE: Determining the prevalence of nasal carriage of S. aureus, both
      sensitive to methicillin and resistant to it, in preschool children and
      evaluating the presence of Panton-Valentine leukocidin genes in the isolates.
      METHODS: This was a cross-sectional study in which cultures from anterior nares
      were obtained from healthy preschool children. Isolates were identified as S.
      aureus based on morphological and biochemical tests. Antibiotic susceptibility
      profiles were determined by the disk diffusion method. All the isolates were
      further analyzed by multiplex PCR to determine the presence of mecA and PVL
      genes; methicillin-resistant isolates were also SCCmec typed by multiplex PCR.
      RESULTS: Overall S. aureus nasal colonization prevalence was 38.5 % and 4.8 % for
      methicillin-resistant strains. All the methicillin-resistant isolates carried the
      genes for PVL; two isolates possessed the SCCmec type IV, two were SCCmec type I
      and one was SCCmec type II. CONCLUSION: This study revealed high PVL-positive,
      methicillin-resistant S. aureus colonization prevalence in healthy preschool
      children from Cartagena, which may play a key role in the epidemiology of
      community-associated infection by methicillin-resistant S. aureus in healthy
      children from this particular geographical area.

PMID- 22634950
TI  - [Oral manifestations and dental caries in children exposed to human
      immunodeficiency virus].
AB  - OBJECTIVE: Determining oral manifestations and dental caries amongst children
      exposed to the immunodeficiency virus (HIV). METHODS: Thirty-seven (n=37)
      children attending the Colombian AIDS Control Program (PRONASIDA-Lara) pediatric
      service were studied. Parents and guardians were informed about the purpose of
      the study and its confidentiality. An oral examination was conducted by a
      dentist; parents/guardians were asked about their children's history of oral
      manifestations and this was corroborated with their clinical charts. RESULTS: The
      mean age was 5.15+/-3.79; 62.2 % were males. Ninety-eight point eight percent had
      become vertically infected. Most of the children were classified in the A immune
      suppression category (35.1 %). The highest percentage (37.8 %) of children were
      in the 15 %-24 % total CD4+ lymphocyte category. The most prevalent oral
      manifestations were oral candidiasis, angular cheilitis, linear gingival erythema
      and parotid enlargement. There was a significant statistical difference between
      percentages of CD4 lymphocytes and angular qualities (p<0.05). Forty-five point
      nine percent had dental caries and 54.1 % were in "urgent" need of dental
      treatment. The Index of Orthodontic Treatment Need (IOTN) showed that 3/4 of the
      children needed dental treatment. CONCLUSIONS: The results of the study led to
      concluding that there was a need for an oral manifestation management-based
      strategy focusing on clinical and preventative treatment, as oral manifestations
      are frequent in children suffering from HIV infection.

PMID- 22634951
TI  - [Prevalence of periodontal disease and oral hygiene indicators in high school
      students from Cartagena, Colombia].
AB  - OBJECTIVE: Determining the prevalence of periodontal disease, treatment needs and
      associated factors in students from the John F. Kennedy School in Cartagena.
      METHODS: This was a cross-sectional study of 392 students selected by
      proportional random sampling stratified to the size of each course, considering a
      population framework of 902 subjects. The Community Periodontal Index of
      Treatment Needs (CPITN) was measured as well as the Green & Vermillon oral
      hygiene index. A univariate analysis was made of percentages and bivariate
      analysis using odds ratios (OR) and 95 % confidence intervals (95 %CI). RESULTS:
      All participants presented at least one disease indicator, the presence of
      calculus being most frequent (45.1 %). Regarding the oral hygiene index, 77.7 %
      of the participants had high bacterial plaque indices. The bivariate analysis
      revealed an association between oral hygiene (OR=2.20; 1.27-3.81 95 %CI) and
      socioeconomic level (OR=0.44; 0.24-0.80 95 %CI). Multivariate analysis led to a
      model being obtained in which gender, socioeconomic level and state of hygiene
      explained periodontal disease severity and treatment needs. CONCLUSIONS:
      Periodontal disease load was extremely high, although most events were found to
      involve early stages, thereby allowing successful intervention to avoid disease
      progressing to advanced stages.

PMID- 22634952
TI  - [Biological fragility syndrome in the elderly: systematic review].
AB  - OBJECTIVE: The aim of this study was to identify the prevalence and assessment
      strategies of Biological Fragility Syndrome in the Elderly. METHODS: For the
      development of this study was it was done a search in electronic databases
      (Medline/PubMed) and the reference lists of articles identified using the
      following key words/terms in English: "frailty" and 'frail" in conjunction with
      the terms "elderly", "aging" and "prevalence". These terms/descriptors were
      combined using the logical operators available in search engines. The initial
      electronic search resulted in 1 865 manuscripts. The process of analysis of the
      studies involved reading titles, abstracts and full texts. After all these
      phases, 35 manuscripts met the inclusion criteria of the review. RESULTS: The
      results indicated that women, with rage from 7.3 % to 21.6 %, are frailer than
      men, with percentages ranging from 4 % to 19.2 %. CONCLUSIONS: Differences in
      prevalence rates of prefrailty and frailty should be minimized, with stimulus for
      standardization for the evaluation of human frailty.

PMID- 22634953
TI  - [A technological device for optimizing the time taken for blind people to learn
      Braille].
AB  - OBJECTIVE: This project was aimed at designing and putting an electronic
      prototype into practice for improving the initial time taken by visually
      handicapped people for learning Braille, especially children. METHODS: This
      project was mainly based on a prototype digital electronic device which
      identifies and translates material written by a user in Braille by a voice
      synthesis system, producing artificial words to determine whether a handicapped
      person's writing in Braille has been correct. A global system for mobile
      communications (GSM) module was also incorporated into the device which allowed
      it to send text messages, thereby involving innovation in the field of articles
      for aiding visually handicapped people. RESULTS: This project's main result was
      an easily accessed and understandable prototype device which improved visually
      handicapped people's initial learning of Braille. CONCLUSIONS: The time taken for
      visually handicapped people to learn Braille became significantly reduced whilst
      their interest increased, as did their concentration time regarding such
      learning.

PMID- 22634955
TI  - Validation of an enzyme immunoassay for the measurement of faecal glucocorticoid
      metabolites in spotted hyenas (Crocuta crocuta).
AB  - The use of enzyme immunoassays (EIAs) to measure faecal glucocorticoid
      metabolites (fGCM) is a useful non-invasive technique to monitor adrenocortical
      activity in vertebrates. The first objective of this study was to validate an 'in
      house' EIA (cortisol-3-CMO) for the measurement of fGCM concentrations in spotted
      hyenas. High-performance liquid chromatography (HPLC) was used to characterise
      fGCM in samples from a captive hyena that received an i.v. injection of [(3)H]
      cortisol. All HPLC fractions were analysed with the EIA for the presence and
      quantities of radiolabelled fGCM. Radiolabelled fGCM consisted of substances with
      a higher polarity than cortisol and substances of lower polarity that eluted
      between cortisol and corticosterone. Authentic radiolabelled cortisol was not
      detected. The EIA measured substantial amounts of immunoreactivity corresponding
      to the radioactive peaks. It also detected a significant increase in fGCMs after
      an adrenocorticotropic hormone (ACTH) challenge in two other captive animals and
      a significant increase in fGCMs in a fourth captive animal after anaesthesia. The
      second objective was to investigate an age effect on fGCM: we conducted pairwise
      comparisons of fGCM concentrations in individual free-ranging juvenile spotted
      hyenas when less than 6 months of age and when between 6 and 24 months of age. We
      expected juveniles to experience a more unpredictable and therefore more
      stressful environment when younger than when older. When younger, juveniles had
      significantly higher fGCM concentrations than when they were older. Our results
      demonstrate that our assay can be used to assess adrenocortical activity in
      spotted hyenas.

PMID- 22634956
TI  - Pit-1w may regulate prolactin gene expression in mouse testis.
AB  - Pit-1 is a POU-domain transcription factor that promotes growth hormone (GH),
      prolactin (PRL), and thyroid-stimulating hormone beta subunit (TSHbeta) gene
      expression in the pituitary gland. Alternative splicing of Pit-1 gene transcripts
      has been shown to give rise to several variants with discrete transactivation
      properties. Recently, we identified a mouse Pit-1 w that is generated by
      alternative promoter usage and is expressed in a variety of tissues including the
      testis. Using a combination of reverse-transcription polymerase chain reaction
      analyses and luciferase reporter gene assays, we investigated the possible role
      of Pit-1 w in the mouse testis. In postnatal testicular development, the
      expression of Pit-1 w mRNA was significantly up-regulated between 18 and 20 days
      after birth when the numbers of secondary spermatocytes and spermatids have been
      reported to increase in mice. The PRL mRNA, but not the mRNAs for GH or TSHbeta,
      showed intratesticular expression patterns that were similar to those of the Pit
      1 w mRNA. In experimental unilaterally cryptorchid testes of adult mice,
      spermatid numbers were extremely low and the expression levels of both the Pit-1
      w and PRL mRNAs dropped dramatically. Furthermore, in the luciferase reporter
      gene assays, we found that Pit-1 w specifically transactivated the PRL promoter
      but had no effect on the promoters of GH or TSHbeta. These results suggested that
      Pit-1 w could be involved in the paracrine/autocrine system in mice and may be
      necessary for normal testicular function via its possible role in regulating PRL
      expression in testicular germ cells. This is the first report demonstrating the
      possible role of Pit-1 w in mammals.

PMID- 22634957
TI  - Structure and expression of a shrimp prohormone convertase 2.
AB  - Although many crustacean neuroendocrine hormones have been reported, the enzymes
      responsible for post-translational modification of neuroendocrine hormones have
      rarely been characterized. A prohormone convertase 2 (PC2)-like enzyme has been
      isolated from the optic lobe of the giant tiger shrimp, Penaeus monodon and
      referred as PmPC2. The full length cDNA sequence of PmPC2 has been identified and
      found to resemble evolutionarily conserved PC2 enzymes of vertebrates and
      invertebrates. PmPC2 was expressed in all larval developmental stages and in
      neuroendrocrine cells in the adult optic lobe. Its expression was found to be
      negatively related with shrimp body weight by qPCR (P<0.05). Immunohistochemistry
      results using an anti-rPmPC2 antibody with adult shrimp revealed high staining
      intensity in specific neurosecretory cells including the sinus gland, the organ
      of Hanstrom (also referred to as the medullar terminalis X-organ) and the organ
      of Bellonci (also referred to as the sensory or X-organ). By using the yeast two
      hybrid technique, PmPC2 was found to bind with P. monodon hyperglycemic hormone
      (Pem-CHH1) that plays an important role in glucose metabolism. Since PmPC2 is a
      subtilisin-like serine proteinase, it is expected to cleave the synthetic
      substrate, pyr-RTKR-MCA, but the expressed recombinant catalytic domain of PmPC2
      (rPmPC2-cat) showed no enzymatic activity as expected. In vivo injection of dsRNA
      PmPC2 resulted in reduced transcripts for both PmPC2 and Pem-CHH1 on day 3 post
      injection, but there was no accompanying reduction of glucose level in the
      hemolymph. Taken together, PmPC2 localization, expression and activity suggest
      that it has a function(s) in the shrimp neuroendrocrine system and that it may
      not only activate Pem-CHH1 but also affect its expression. However, there is no
      obvious explanation for the negative correlation between PmPC2 expression level
      and shrimp body weight.

PMID- 22634958
TI  - Stimulatory effect of SOM230 on human and rat adrenal corticosteroid secretion in
      vitro.
AB  - SOM230 (pasireotide, Signifor), a recently developed somatostatin analog, has
      been tested in ACTH-secreting pituitary tumors with promising results. No study
      has yet evaluated whether this analog also directly affects adrenal steroid
      production. The aim of the current study was to evaluate whether SOM230 modulates
      corticosteroid secretion by normal adrenals in vitro. Primary cultures from
      normal human and rat adrenals were incubated with 10-100 nM SOM230 with and
      without 10nM ACTH. Dose-response studies with 1 nM-1 MUM SOM230 were performed on
      rat adrenals. Cortisol/corticosterone levels in medium were measured after 4 and
      24h. SOM230 (10nM) significantly increased corticosteroid levels after 24h
      incubation in both human (36.4 +/- 0.43 ng/well vs 27.7 +/- 3.17 ng/well, p<0.05)
      and rat (16.2 +/- 1.16 ng/well vs 11.6 +/- 0.92 ng/well p<0.05) adrenals; lesser
      effects were observed with 100 nM SOM (33.4 +/- 2.59 ng/well vs 27.7 +/- 3.17
      ng/well p<0.05; 13.4 +/- 0.82 ng/well vs 11.6 +/- 0.92 ng/well, N.S. vs baseline
      secretion for human and rat adrenals, respectively). Dose-response curves
      confirmed maximal effect at 10nM SOM230. The corticosteroid secretory response to
      ACTH was unaffected by SOM230 co-incubation. In conclusion, SOM230 exerts a
      moderate stimulatory effect on adrenal corticosteroid secretion in vitro. This
      argues against a direct adrenal involvement in the clinical efficacy of SOM230 in
      patients with ACTH-secreting pituitary tumors and widens the known range of
      action of SOM230.

PMID- 22634959
TI  - A quasi-experimental study of Chinese top-level speed skaters' training load:
      threshold versus polarized model.
AB  - PURPOSE: To examine the effectiveness of threshold and polarized models in the
      training organization of Chinese top-level sprint speed skaters using a 2-y quasi
      experimental design. METHODS: Two years (2004-05 and 2005-06 seasons) of the
      Chinese national speed-skating team's daily training load (N = 9; 5 men, 23.6 +/-
      1.7 y, weight 76.6 +/- 4.1 kg, competitive experience 5.0 +/- 0.8 y, 500-m time
      35.45 +/- 0.72 s, 1000-m time 71.18 +/- 2.28 s; 4 women, 25.3 +/- 6.8 y, 73.0 +/-
      8.5 kg, 6.3 +/- 3.5 y, 37.81 +/- 0.46 s, 75.70 +/- 0.81 s) were collected and
      analyzed. Each season's training load included overall duration (calculated in
      min and km), frequency (calculated by overall sessions), and training intensity
      (measured by ear blood lactate or estimated by heart rate), Their performances at
      national, World Cup, and Olympic competitions during the 2 seasons (2004-06), as
      well as lactate data measured 15 and 30 min after these competitions, were also
      collected and analyzed. Based on the lactate data (<2, 2-4, >4 mmol/L), training
      zones were classified as low, moderate, and high intensity. RESULTS: The total
      durations and frequencies of the training load were similar across the seasons,
      but a threshold-training model distribution was used in 2004-05, and a polarized-
      raining-load organization in 2005-06. Under the polarized-training model, or load
      organization, all speed skaters' performance improved and their lactate after
      competition decreased considerably. CONCLUSION: Training-intensity distribution
      based on a polarized-training model led to the success in top Chinese sprint
      speed skaters in the 2005-06 season.

PMID- 22634964
TI  - Reliability and effect of sodium bicarbonate: buffering and 2000-m rowing
      performance.
AB  - PURPOSE: The aim of this study was to determine the effect and reliability of
      acute and chronic sodium bicarbonate ingestion for 2000-m rowing ergometer
      performance (watts) and blood bicarbonate concentration [HCO3-]. METHODS: In a
      crossover study, 7 well-trained rowers performed paired 2000-m rowing ergometer
      trials under 3 double-blinded conditions: (1) 0.3 grams per kilogram of body mass
      (g/kg BM) acute bicarbonate; (2) 0.5 g/kg BM daily chronic bicarbonate for 3 d;
      and (3) calcium carbonate placebo, in semi-counterbalanced order. For 2000-m
      performance and [HCO3-], we examined differences in effects between conditions
      via pairwise comparisons, with differences interpreted in relation to the
      likelihood of exceeding smallest worthwhile change thresholds for each variable.
      We also calculated the within-subject variation (percent typical error). RESULTS:
      There were only trivial differences in 2000-m performance between placebo (277 +/
      60 W), acute bicarbonate (280 +/- 65 W) and chronic bicarbonate (282 +/- 65 W);
      however, [HCO3-] was substantially greater after acute bicarbonate, than with
      chronic loading and placebo. Typical error for 2000-m mean power was 2.1% (90%
      confidence interval 1.4 to 4.0%) for acute bicarbonate, 3.6% (2.5 to 7.0%) for
      chronic bicarbonate, and 1.6% (1.1 to 3.0%) for placebo. Postsupplementation
      [HCO3-] typical error was 7.3% (5.0 to 14.5%) for acute bicarbonate, 2.9% (2.0 to
      5.7%) for chronic bicarbonate and 6.0% (1.4 to 11.9%) for placebo. CONCLUSION:
      Performance in 2000-m rowing ergometer trials may not substantially improve after
      acute or chronic bicarbonate loading. However, performances will be reliable with
      both acute and chronic bicarbonate loading protocols.

PMID- 22634967
TI  - Use of ratings of perceived exertion in sports.
AB  - The rating of perceived exertion (RPE) is a recognized marker of intensity and of
      homeostatic disturbance during exercise. It is typically monitored during
      exercise tests to complement other measures of intensity. The purpose of this
      commentary is to highlight the remarkable value of RPE as a psychophysiological
      integrator in adults. It can be used in such diverse fashions as to predict
      exercise capacity, assess changes in training status, and explain changes in pace
      and pacing strategy. In addition to using RPE to self-regulate exercise, a novel
      application of the intensity:RPE relationship is to clamp RPE at various levels
      to produce self-paced bouts of exercise, which can be used to assess maximal
      functional capacity. Research also shows that the rate of increase in RPE during
      self-paced competitive events of varying distance, or constant-load tasks where
      the participant exercises until volitional exhaustion, is proportional to the
      duration that remains. These findings suggest that the brain regulates RPE and
      performance in an anticipatory manner based on awareness of metabolic reserves at
      the start of an event and certainty of the anticipated end point. Changes in pace
      may be explained by a continuous internal negotiation of momentary RPE compared
      with a preplanned "ideal rate of RPE progression" template, which takes into
      account the portion of distance covered and the anticipated end point. These
      observations have led to the development of new techniques to analyze the complex
      relationship of RPE and pacing. The use of techniques to assess frontal-cortex
      activity will lead to further advances in understanding.

PMID- 22634968
TI  - Current match-analysis techniques' underestimation of intense periods of high
      velocity running.
AB  - PURPOSE: To compare the peak 5-min period of high-velocity running (HiVR) during
      a soccer match using a predefined vs a rolling time interval. METHODS: Player
      movement data were collected from 19 elite Australian soccer players over 11
      competitive matches (77 individual match files) using a 5-Hz global-positioning
      system. Raw velocity data were analyzed to determine the period containing the
      greatest HiVR distance per match half and the distance covered in the subsequent
      epoch. Intervals were identified using either a predefined (distance covered in 5
      min at every 5-min time point) or rolling (distance covered in 5 min from every
      time point) method. The percentage difference +/- 90% confidence limits were used
      to determine differences between methods. RESULTS: Predefined periods
      underestimated peak distance covered by up to 25% and overestimated the
      subsequent epoch by up to 31% compared with rolling periods. When the distance
      decrement between the peak and following period was determined, there was up to a
      52% greater reduction in running performance using rolling periods than
      predefined ones. CONCLUSIONS: It is recommended that researchers use rolling as
      opposed to predefined periods when determining specific match intervals because
      they provide a more accurate representation of the HiVR distance covered. This
      will avoid underestimation of both match running distance and the decrement in
      running performance after an intense period of play. This may have practical
      implications for not only researchers but also staff involved in a club setting
      who use this reduction as evidence of transient fatigue during a match.

PMID- 22634969
TI  - Warm-up intensity and duration's effect on traditional rowing time-trial
      performance.
AB  - The warm-up procedure in traditional rowing usually involves continuous low
      intensity rowing and short bouts of intense exercise, lasting about 60 min.
      PURPOSE: To compare the effects of a traditional and an experimental 30-min warm
      up of lower intensity on indoor rowing time-trial performance. METHODS: Fourteen
      highly trained male rowers (age 25.9 +/- 5.3 y, height 1.86 +/- 0.06 m, mass 80.4
      +/- 5.2 kg, peak aerobic power 352.0 +/- 24.4 W; mean +/- SD) performed 2 indoor
      rowing trials 12 d apart. Rowers were randomly assigned to either LONG or SHORT
      warm-ups using a crossover design, each followed by a 10-min all-out fixed-seat
      rowing-ergometer time trial. RESULTS: Mean power output during the time trial was
      substantially higher after SHORT (322 +/- 18 vs 316 +/- 17 W), with rowers
      generating substantially more power in the initial 7.5 min of the time trial
      after SHORT. LONG elicited substantially higher mean warm-up heart rate than
      SHORT (134 +/- 11 vs 121 +/- 13 beats/min), higher pre-time-trial rating of
      perceived exertion (10.2 +/- 1.4 vs 7.6 +/- 1.7) and blood lactate (1.7 +/- 0.4
      mM vs 1.2 +/- 0.2 mM), but similar heart rate (100 +/- 14 vs 102 +/- 9
      beats/min). No substantial differences were observed between LONG and SHORT in
      stroke rate (39.4 +/- 2.0 vs 39.4 +/- 2.2 strokes/min) or mean heart rate (171 +/
      6 vs 171 +/- 8 beats/min) during the time trial, nor in blood lactate after it
      (11.8 +/- 2.5 vs 12.1 +/- 2.0 mM). CONCLUSION: A warm-up characterized by lower
      intensity and shorter duration should elicit less physiological strain and
      promote substantially higher power production in the initial stages of a rowing
      time trial.

PMID- 22634970
TI  - Seasonal changes in fitness parameters in a world champion rowing crew.
AB  - PURPOSE: To examine variations in physical, physiological, and performance
      parameters over an annual training cycle in a world champion rowing crew.
      METHODS: Four world-class rowers, all of them members of the men's heavyweight
      quadruple sculls squad who are current world rowing champions, were assessed 3
      times at regular 4-mo intervals during the 2011 season (November 2010, March
      2011, and July 2011). Physical assessments included stature, body mass, body
      composition, whereas physiological and performance assessments obtained during an
      incremental rowing ergometer test to exhaustion included maximum oxygen uptake
      and anaerobic gas-exchange threshold with corresponding power output values.
      RESULTS: Body mass (~95 kg) and body composition (~12% body fat) remained stable
      over the annual training cycle. Power output at anaerobic gas-exchange threshold
      increased +16% from November to July, whereas the corresponding oxygen uptake,
      expressed as a percentage of maximum oxygen uptake, increased from 83% to 90%.
      Maximum oxygen uptake decreased from 6.68 L/min in November to 6.10 L/min in
      March before rising to 6.51 L/min in July. The corresponding power output
      increased steadily from 450 W to 481 W. CONCLUSION: Seasonal variation in body
      mass and body composition of 4 examined world-class rowers was minimal. Oxygen
      uptake and power output corresponding to anaerobic threshold continuously
      increased from off-season to peak competition season. Seasonal variation in
      maximum oxygen uptake reached ~10%; however, it remained above 6 L/min, that is,
      the value consistently observed in top caliber heavyweight rowers regardless of
      the time of the assessment.

PMID- 22634971
TI  - Training distribution, physiological profile, and performance for a male
      international 1500-m runner.
AB  - This case study observed the training delivered by a 1500-m runner and the
      physiological and performance change during a 2-y period. A male international
      1500-m runner (personal best 3:38.9 min:s, age 26 y, height 1.86 m, body mass 76
      kg) completed 6 laboratory tests and 14 monitored training sessions, during 2
      training years. Training distribution and volume was ascertained from training
      diary and spot-check monitoring of heart rate and accelerometry measurements.
      Testing and training information were discussed with coach and athlete from which
      training changes were made. In the first training year, low-intensity training
      was found to be performed above the prescribed level, which was adjusted with
      training and coach support in y 2 (training zone < 80% of vVO2max, y 1 = 20%; y 2
      = 55%). "Tempo" training was also performed at an excessively high intensity
      (Delta [blood lactate] 5-25 min of tempo run, y 1 = Delta6.7 mM, y 2 = Delta2.5
      mM). From y 1 to 2, there was a concomitant increase in the proportion of
      training in the high-intensity zone of 100 to 130% vVO2max from 7 to 10%. Values
      for VO2max increased from 72 to 79 mL . kg-1 . min, economy improved from 210 to
      206 mL . kg-1 . min, and 1500-m performance time improved from 3:38.9 to 3:32.4
      min:s from the beginning of y 1 to the end of y 2. This case shows a modification
      in training methodology that was coincident with a greater improvement in
      physiological capability and furtherance in performance improvement.

PMID- 22634972
TI  - Kenyan and Ethiopian distance runners: what makes them so good?
AB  - Since the 1968 Mexico City Olympics, Kenyan and Ethiopian runners have dominated
      the middle- and long-distance events in athletics and have exhibited comparable
      dominance in international cross-country and road-racing competition. Several
      factors have been proposed to explain the extraordinary success of the Kenyan and
      Ethiopian distance runners, including (1) genetic predisposition, (2) development
      of a high maximal oxygen uptake as a result of extensive walking and running at
      an early age, (3) relatively high hemoglobin and hematocrit, (4) development of
      good metabolic "economy/efficiency" based on somatotype and lower limb
      characteristics, (5) favorable skeletal-muscle-fiber composition and oxidative
      enzyme profile, (6) traditional Kenyan/Ethiopian diet, (7) living and training at
      altitude, and (8) motivation to achieve economic success. Some of these factors
      have been examined objectively in the laboratory and field, whereas others have
      been evaluated from an observational perspective. The purpose of this article is
      to present the current data relative to factors that potentially contribute to
      the unprecedented success of Kenyan and Ethiopian distance runners, including
      recent studies that examined potential links between Kenyan and Ethiopian
      genotype characteristics and elite running performance. In general, it appears
      that Kenyan and Ethiopian distance-running success is not based on a unique
      genetic or physiological characteristic. Rather, it appears to be the result of
      favorable somatotypical characteristics lending to exceptional biomechanical and
      metabolic economy/efficiency; chronic exposure to altitude in combination with
      moderate-volume, high-intensity training (live high + train high), and a strong
      psychological motivation to succeed athletically for the purpose of economic and
      social advancement.

PMID- 22634973
TI  - Superficial vein thrombosis: a consensus statement.

PMID- 22634974
TI  - UIP consensus on corona phlebectatica.

PMID- 22634975
TI  - Prediction of vascular events in subjects with subclinical atherosclerosis and
      the metabolic syndrome: the role of markers of inflammation.
AB  - AIM: The presence of the metabolic syndrome (MS) increases cardiovascular
      morbidity and mortality and we aimed to assess the outcome in subjects with the
      MS and subclinical atherosclerosis. METHODS: We followed-up for five years 339
      Mediterranean subjects with asymptomatic carotid intima-media thickness >0.9 mm
      (men: 60%; age: 66+/-5 years), of whom 130 had the MS (men: 59%; age: 66+/-5
      years), evaluating at baseline traditional cardiovascular risk factors (including
      male gender, older age, obesity, hypertension, diabetes, smoking, family history
      of cardiovascular diseases, dyslipidemia) and plasma levels of C-reactive protein
      and fibrinogen. RESULTS: Cardio- and cerebrovascular events were registered in
      the 29% of subjects with the MS and in the 20% of those without it and the
      presence of more criteria for the diagnosis of the MS was significantly
      associated with vascular morbidity and mortality. By multivariate analysis,
      including all baseline variables, independent predictive roles for the events
      were found for elevated markers of inflammation (OR 3.8), elevated fasting
      glucose (OR 2.1) and elevated triglycerides (OR 1.4). CONCLUSION: These findings
      confirm a worst vascular outcome in subjects with more criteria for the diagnosis
      of the MS and further suggest the need of future research to understand the
      combined role of inflammation and the MS in the progression from subclinical to
      clinical atherosclerosis.

PMID- 22634976
TI  - Epidemiologic aspects of abnormal ankle brachial index in the HIV infected
      population.
AB  - AIM: HIV infection is strongly associated with accelerated vascular
      atherosclerosis and increased cardiovascular events. The prevalence of peripheral
      arterial disease (PAD) in HIV infected patients is not clearly defined and the
      results of different reports are contradicting. OBJECTIVE: To determine the
      prevalence of abnormal Ankle Brachial Index (ABI) and associated risk factors in
      HIV infected population. METHODS: The ABI was measured manually using 5.0 MHz
      handheld Doppler probe in 173 HIV infected patients. The cohort was categorized
      according to the ABI measurements as; normal group (ABI 0.9 to 1.3), peripheral
      arterial disease (PAD) group (ABI<0.9), and High ABI group (ABI>1.3). Several
      demographic, atherosclerosis risk factors and HIV infection parameters have been
      evaluated as potential risk factors. RESULTS: Median age of the cohort was 49
      years (inter-quartile ranges [IQR]: 42.5 to 54); 63.4% were males. Abnormal ABI
      was found in 47(27.2%) patients; twenty four (13.9%) had PAD and 23(13.3%) had
      high ABI. Among the risk factors evaluated, we observed that PAD group is
      associated with diabetes (Relative risk [RR]: 4.19; 95% confidence interval [CL]:
      2.13 to 8.27; P=0.0002) and age above 49 (Relative risk [RR]: 3.96; 95%
      confidence interval [CL]: 1.56 to 10.0; P=0.002). However, the High ABI group was
      significantly associated with male gender (RR: 3.94; 95% CI: 1.23 to 12.70;
      P=0.009). CONCLUSION: HIV infection is associated with increased prevalence of
      abnormal resting ABI.

PMID- 22634977
TI  - The vein collar: an anastomotic servant or a patency promoter? Re-analysis of a
      randomized trial.
AB  - AIM: Randomized studies evaluating the effect of a vein collar at the distal
      anastomosis of PTFE-grafts show conflicting results. The study of the Joint
      Vascular Research Group (JVRG) of UK found improved primary patency while the
      Scandinavian Miller Collar Study (SCAMICOS) found neither any effect on patency
      nor on limb salvage after bypass to below-knee arteries. It has been discussed
      whether the questioned positive effect of a vein collar is due to technical
      advantages when the anastomosis is made rather than on a positive influence on
      the long-term effect by less pseudointima formation. METHODS: Primary patency
      regarding the use of vein collar were re-analyzed in 345 patients from SCAMICOS
      with Kaplan-Meier life-table technique and Cox proportional hazards regression in
      a counting process notation to evaluate any interaction between time-period and
      the effect of a vein collar on the primary patency rate. RESULTS: No overall
      effect on primary patency of a vein collar at the distal anastomosis was found
      irrespective of the site anastomosis. However, during the first 30 days of follow
      up the primary patency among the femoro-crural bypasses was 0.87 (0.79-0.95) and
      0.72 (0.63-0.83) with and without vein collar respectively. The interaction
      between vein collar and time-period was not statistically significant (P=0.070)
      and neither was the Score test for the whole interaction analysis (P=0.091) for
      the patients with anastomosis to the crural arteries. No such initial differences
      were found for the patients with anastomosis to the popliteal artery below-knee.
      CONCLUSION: A clinically relevant but not statistically significant better
      primary patency during the first 30 days was found for patients with PTFE-bypass
      to the crural arteries with a vein collar at the distal anastomosis. There were
      no long-term advantages of the vein collar irrespective of the location of the
      anastomosis.

PMID- 22634978
TI  - Tibial angioplasty in diabetic patients: should all vessels be treated?
AB  - AIM: Patients with severe critical limb ischemia (CLI) due to tibial disease are
      commonly treated nowadays with tibial angioplasty. However, the benefits and
      complications of treating "more than one tibial vessel" have not yet been
      determined. This study compares the outcome of angioplasty of one vessel versus
      that of more than one vessel in patients with CLI due to tibial disease. METHODS:
      We retrospectively reviewed all consecutive diabetic patients with tibial disease
      with no concomitant proximal lesions who were treated by angioplasty. Among 82
      patients with isolated tibial disease 48 patients were selected. All patients had
      to have more than one diseased tibial vessel that can be treated by angioplasty.
      Group A patients (N.=25) had only one tibial vessel treated while group B
      patients (N.=23) had more than one tibial vessel treated. We compared both groups
      with respect to patients' characteristics, lesion morphology, and limb salvage
      rate. RESULTS: Lesion morphology was worse in group A than B: anterior tibial
      artery showed more long lesions (17 vs. 8), more multiple lesions (22 vs. 11),
      and peroneal artery showed more long lesions (23 vs. 10), more multiple lesions
      (24 vs. 12), and more occlusions (18 vs. 10). Limb salvage rate at 12 months was
      similar (91%) in both groups. There were 5 complications in each group.
      CONCLUSION: The lesion morphology was worse in group A. Simpler lesions in group
      B motivated performing more than one vessel angioplasty. There was no difference
      in the limb salvage rate in the medium term among both groups. Additional vessels
      angioplasty in less diseased arteries was not associated with substantial
      additional morbidity.

PMID- 22634979
TI  - Infrapopliteal arterial occlusive disease in elderly men: a population based
      study.
AB  - AIM: The aim of this paper was to determine prevalence, cardiovascular risk
      factors and association with coronary heart disease (CHD) of isolated
      infrapopliteal arterial disease in old-adult men. METHODS:  DESIGN: cross
      sectional; participants: population-based sample of 699 men aged 55 to 74 years,
      measurements: cardiovascular history and risk factors, electrocardiogram,
      segmental pressures and velocity waveforms in lower limbs. RESULTS: Peripheral
      arterial occlusive disease (PAOD) was observed in 13.4% subjects, of whom 39.4%
      (37 patients) had isolated infrapopliteal PAOD. Of these, 11 (29.7%) patients
      were symptomatic. Isolated infrapopliteal PAOD was significantly associated with
      increased age, smoking, diabetes and hypertriglyceridemia. Subjects with extended
      PAOD differed from those with isolated infrapopliteal PAOD in increased tobacco
      exposure, higher levels of LDL and lower levels of HDL cholesterol. Association
      between PAOD and CHD was almost always significant (odds ratio from 1.8 to 3.4)
      irrespective of PAOD topographic pattern and symptom characteristics of CHD
      subjects. CONCLUSION: Isolated infrapopliteal PAOD is a frequent asymptomatic
      disorder in old-adult men, clearly associated with both symptomatic and
      asymptomatic CHD. In contrast to an expected risk factor profile biased by
      clinical practice, these subjects only differed from those with PAOD
      significantly extended to proximal arteries in their smoking exposition and a
      more atherogenic lipid profile.

PMID- 22634980
TI  - Distribution of brachial-ankle pulse wave velocity values and optimal cut-off in
      distinguishing subjects with clinical condition in Chinese population.
AB  - AIM: The present study aims to examine the distribution and gender- and age
      specific reference ranges of brachial-ankle pulse wave velocity (baPWV) in
      Chinese population. METHODS: A total of 21094 subjects were recruited into a
      cross-sectional study from June 2007 to June 2008 in China. Participants were
      divided into three clinical subgroups: 1) subgroup 1: subjects with
      atherosclerotic cardiovascular diseases; 2) subgroup 2: subjects with
      atherosclerotic risk factors; and 3) subgroup 3: "healthy subjects" without any
      atherosclerotic cardiovascular diseases and atherosclerotic risk factors.
      RESULTS: The average baPWV among subgroups one through 3 was 1724.3+/-429.1,
      1603.5+/-358.8, and 1389.9+/-288.4 cm/s, respectively. BaPWV did not fit as a
      normal distribution in both genders. There was no significant difference between
      male and female for baPWV in subgroup 1 (P>0.05). While baPWV was higher in
      females than males in subgroup 2, it was lower in females than in males in
      subgroup 3 (all P<0.05). Notably, BaPWV significantly increased with age in both
      genders (all P for trend<0.05). The receiver operator characteristic curve
      demonstrated that a baPWV of 1450 cm/s was useful to discriminate either
      cardiovascular diseases or atherosclerotic risk factors (sensitivity 62.1%,
      specificity 69.5%), a baPWV of 1551 cm/s was useful to discriminate
      cardiovascular diseases (sensitivity 62%, specificity 61%), and a baPWV of 1566
      cm/s was useful to discriminate either cardiovascular diseases or chronic kidney
      disease (sensitivity 60%, specificity 63%). CONCLUSION: The reference ranges and
      cut-off values of baPWV can be used to screen atherosclerotic cardiovascular
      diseases in clinical practices.

PMID- 22634981
TI  - Beware of suboptimal medical management of patients with atherosclerosis
      requiring revascularization.
AB  - AIM: The aim of this paper was to assess a daily-life evaluation of vascular risk
      factor control, pharmacological treatment and prognosis in patients with
      atherosclerosis referred for revascularization. METHODS: Prospective
      observational study conducted in a French University Hospital with collection of
      atherosclerosis referral site information, reported patient history, documented
      atherosclerosis sites seen on examination, biological data, and clinical
      outcomes. RESULTS: 956 patients (82.6% men, 64.5+/-10.1 years) were enrolled for
      supra-aortic vessel disease (SVD, 24.6%), coronary heart disease (CHD, 40.4%),
      peripheral artery occlusive disease (PAOD, 34.2%), and visceral artery disease
      (1.7%). Involvement of >2 vascular territories was documented in 85%. Vascular
      risk factor frequency results were: previous (65.7%) or current (10.6%) tobacco
      use, hypertension (64.3%), hyperlipidaemia (75.4%), diabetes (25.8%), overweight
      (43.8%), and obesity (25.2%). LDL-cholesterol was >100 mg/dL for 38.1%, most
      frequently seen in patients with PAOD referral (P<0.001) or history (P=0.002),
      and for 29.2% of the patients taking a statin. HbA1c levels were >6.5% for 53.8%
      of patients with diabetes. The triple combination of an antiplatelet agent, a
      statin, and a renin-angiotensin-system inhibitor was not prescribed often enough,
      especially for PAOD referrals (PAOD referrals, 45.1%; SVD referrals, 48.1%; CHD
      referrals, 65.9%). Independent risk factors for all-cause mortality were: a
      previous CHD or PAOD clinical event, body mass index <25 kg/m2, HbA1c >6.5%, and
      no aspirin treatment. CONCLUSION: Even at the time of revascularization, medical
      management of atherosclerosis was not optimal. The need for continuing education
      of physicians and patients remains essential.

PMID- 22634982
TI  - Low attendance of patients with intermittent claudication in a German community
      based walking exercise program.
AB  - AIM: Exercise therapy is an efficacious treatment for patients with peripheral
      arterial disease (PAD). The study aimed to determine the initiation and adherence
      of PAD patients with intermittent claudication in a supervised community-based
      walking exercise program. METHODS: Over a period of one year, PAD patients with
      Fontaine stage II attending an angiological outpatient setting were consecutively
      recruited to the study. Willingness, commencement and adherence of patients in
      the training program were recorded. RESULTS: Of 462 patients with intermittent
      claudication, only 166 (36%) subjects fulfilled the requirements for
      participation in physical exercise training. Of these eligible patients, 110
      (66%) persons accepted the invitation to attend exercise therapy. However,
      despite the commitment, 58 (35%) subjects failed to initiate attendance in the
      training program. Fifty-two (24%) patients did start the program but 16 (8%)
      patients did not complete more than three initial training sessions. Over a three
      month period, regular attendance was registered for 36 (16%) patients.
      CONCLUSION: Although physical exercise improves symptoms and mobility of patients
      with intermittent claudication, only about one-third of them is commencing an
      exercise program. Through lacking initiation and discontinuation, only a small
      percentage of claudicants permanently engages in a walking exercise program.

PMID- 22634983
TI  - Patterns of markers of inflammation, coagulation and vasoconstriction during
      follow-up of abdominal aortic aneurysms.
AB  - AIM: The etiology of abdominal aortic aneurysm (AAA) includes inflammation,
      coagulation, and endothelial dysfunction. We have prospectively evaluated
      relations between these mechanisms and AAA growth. Tumour necrosis factor (TNF)
      alpha, interleukin (IL)-6, endothelin (ET)-1, CD40 ligand and the complex formed
      between activated protein C (APC) and protein C inhibitor (PCI) were measured
      annually and related to AAA growth during up to 5 years in 206 patients with
      conservatively followed AAA. METHODS: We evaluated 163 patients up to 1 year, 126
      patients up to 2 years, 83 patients up to 3 years, 53 patients up to 4 years, and
      33 patients up to 5 years. The total number of patient follow-up years was 458.
      RESULTS: ET-1 remained unchanged except for a tendency to increase in the third
      and fourth years of follow-up. TNF-alpha decreased significantly during the first
      year and thereafter increased back to baseline values. There were no changes in
      IL-6, CD40 ligand, and APC-PCI complex. When patients in the highest and lowest
      quartiles of AAA growth up to 5 years follow-up were compared, APC-PCI complex
      levels tended to be higher (P=0.06) in the highest quartile of growth at three
      years (0.45 ug/l [i.q.r. 0.40-0.77] versus 0.28 ug/L [i.q.r. 0.14-0.36]). Delta
      values of ET-1 and TNF-alpha did not show any correlation to growth. The 14 AAA
      patients that ruptured during follow-up did not differ from patients with non
      ruptured AAA regarding biomarkers. CONCLUSION: In conclusion, none of the
      investigated mediators could be used to predict growth or rupture, or help to
      prolong intervals between ultrasound examinations in follow-up of AAA patients.

PMID- 22634984
TI  - Cancer as a risk factor for residual pulmonary embolism.
AB  - AIM: Despite anticoagulation in some patients after pulmonary embolism (PE)
      pulmonary emboli are not completely resolved. The goal of our prospective study
      was to evaluate the rate of residual pulmonary emboli in repeated CT
      pulmoangiography 13-17 weeks after setting the diagnosis of PE and to determine
      the relationship between primary risk factors for PE, the results of the primary
      entry tests and the incidence of residual pulmonary embolism. METHODS: Fifty
      three patients aged 59.8 (54.9-67.7) years with confirmed first episode of PE
      were enrolled into the study, 37 patients after appropriate anticoagulation
      underwent the repeated CT pulmoangiography. RESULTS: This examination confirmed
      the presence of embolic residues in pulmonary arteries in 8 patients (21.6%).
      After analyzing the observed entry (by admission to the hospital with the
      diagnosis of PE) parameters (age, sex, systolic and diastolic blood pressure,
      heart rate, waist circumference, body weight, body mass index, presence of
      hypertension, diabetes mellitus type 2, the presence of inflammatory disease,
      immobilization, recent surgery or overcome trauma, history of malignancy, venous
      thromboembolism in the past, previous treatment with statins, CRP, troponin T,
      TSH, D-dimer, total cholesterol, LDL cholesterol, HDL cholesterol, serum
      trigylcerides) the authors note that the only parameter that was significantly
      associated with persisting embolic residues was malignancy (2/29 patients without
      residues vs. 4/8 patients with residues, odds ratio=13.5, 95%CI=1.8344-99.35,
      P=0.0106). There was no statistically significant difference in other observed
      parameters. CONCLUSION: Malingnancy represents an important predictor of
      incomplete recanalization of pulmonary arteries after the first episode of
      pulmonary embolism.

PMID- 22634985
TI  - Catheter-directed thrombolysis with microplasmin for acute peripheral arterial
      occlusion (PAO): an exploratory study.
AB  - AIM: We performed an open-label, dose-ascending, single-centre, Phase IIa study
      to explore the safety and efficacy of catheter-directed thrombolysis (CDT) with
      microplasmin for infrainguinal arterial or bypass occlusions. METHODS: Patients
      who presented with acute occlusions were subsequently treated with an
      intrathrombus infusion of five ascending doses of microplasmin: 0.3 mg/kg/h for 4
      hours; 0.45 mg/kg/h for 4 hours; 0.6 mg/kg/h for 4 hours; 0.9 mg/kg/h for 4 hours
      or 0.6 mg/kg/h for 6 hours. Repeat angiograms were obtained to assess the degree
      of clot lysis. The primary outcome was complete thrombolysis defined as >95%
      thrombus volume reduction at the end of the microplasmin infusion. Safety
      evaluation included bleedings, adverse events and coagulation biomarkers.
      RESULTS: Complete thrombolysis was obtained in 3 of the 19 treated patients at
      the end of microplasmin infusion. Thrombus volume reduction between 50% and 95%
      was achieved with all dosing regimens. Clinically significant distal embolization
      occurred in 8 patients. One major and two non-major bleedings occurred.
      Microplasmin depleted alpha2-anti-plasmin and decreased fibrinogen. CONCLUSION:
      Intrathrombus infusion of microplasmin for 4 or 6 hours resulted in significant
      clot lysis. Distal embolization appeared the most important limitation.

PMID- 22634986
TI  - Writing a research abstract: eloquence in miniature.
AB  - Abstracts are summaries, usually of a full article or conference presentation,
      and may be classified into structured and unstructured ones. The former have a
      predefined layout necessitating the use of headings. Most journals and
      conferences now use the structured abstract format. Research abstracts are
      increasingly vital for scientific communication and are expected to continue
      playing a key role for the dissemination of medicine in the near future.
      Abstracts take time and need meticulous preparation. They must aptly summarise
      the content of the study or presentation and avoid vague statements and poor
      style. Moreover, they must comply with provided instructions. Finally, they
      should be pleasant to read and encourage study of the corresponding full work.

PMID- 22634987
TI  - Use of porcine dermal collagen implant for definite early closure of the open
      abdomen in aortic surgery.

PMID- 22634988
TI  - Predictive risk of mortality in the endovascular approach of Stanford type B
      complicated aortic dissection.

PMID- 22634989
TI  - The management of cyclic vomiting syndrome:  a systematic review.
AB  - Cyclic vomiting syndrome (CVS) is a rare abnormality of the neuroendocrine system
      that affects 2% of children. It is a frequently missed diagnosis in the emergency
      department and may require a number of emergency department visits before the
      diagnosis is made. The objectives of this review are to identify the clinical
      features that suggest a diagnosis of CVS and to review the literature on its
      management. The MEDLINE and EMBASE databases were searched from January 1948 to
      October 2011 using the keywords 'Cyclic' or 'Vomiting'. Papers were excluded if
      they did not follow the consensus guidelines or if they were case reports. This
      review analysed 1093 cases of cyclic vomiting in 25 papers that fulfilled the
      inclusion criteria. All except one paper were retrospective studies. The size of
      these cohort studies ranged from three to 181 patients, with a mean patient size
      of 29. This review found that over 40% of patients have headaches/migraines, with
      associated anxiety and depression in ~ 30% of cases. There is a family history of
      headaches/migraines in 38.9%, and this association was much stronger in the adult
      CVS cohort compared with the paediatric cohort. Compared with paediatric CVS,
      adults have a longer duration of attacks and they occur more frequently (5.9 vs.
      3.4 days, 14.4 vs. 9.6 episodes/year). Limited data are available on the
      treatment of the acute phase of CVS, but in adults, sumatriptan has been shown to
      be effective. For prophylactic treatment, tricyclics are effective in both adult
      and paediatric CVS, with a clinical response in 75.5 and 67.6% of patients,
      respectively, in nonplacebo-controlled cohort studies. Furthermore, propranolol
      has been shown to be useful in children. CVS is an intractable illness with a
      major impact on the patient's quality of life. There is a long duration between
      the onset of symptoms and the diagnosis of the condition. There is a high
      association with headaches/migraines and anxiety/depression. The symptoms are
      more severe in adult-onset CVS. Tricyclic antidepressants have good efficacy in
      reducing the frequency/duration or the intensity of attacks. There is limited
      evidence on the acute management of CVS.

PMID- 22634990
TI  - NECOBELAC supporting Open Access, a path to open science.

PMID- 22634991
TI  - [Experience of implementing a primary attention model].
AB  - OBJECTIVE: Identifying barriers and dynamic factors in setting up a primary
      health care (PHC) model in the Santander department during the last decade.
      METHODS: This was a qualitative study, focusing on pluralism and triangulating
      sources and actors, with a critical analysis of limits and judgments values
      (boundary critique). RESULTS: Philosophical/conceptual and operational management
      problems were found from the emergent categories related to appropriating PHC
      attributes. The theoretical model design was in fact not developed in practice.
      The PHC strategy is selective and state-led (at department level), focusing on
      rural interventions developed by nursing assistants and orientated towards
      fulfilling public health goals in the first healthcare level. CONCLUSION:
      Difficulties at national, state and local level were identified which could be
      useful in other national and international contexts. Structural healthcare system
      market barriers were the most important constraints since the model operates
      through the contractual logic of institutional segmentation and operational
      fragmentation. Human resource management focusing on skills, suitable local
      health management and systematic evaluation studies would thus be suggested as
      essential operational elements for facing the aforementioned problems and
      encourage an integral PHC model in Colombia.

PMID- 22634993
TI  - [Symptoms of anxiety and depression in adolescents between 10 to 17 year-old
      attending schools in Chia, Colombia].
AB  - OBJECTIVE: This study was aimed at estimating the prevalence of symptoms of
      depression and anxiety amongst 10 to 17 year-old adolescents still attending
      school using the CDI and SCARED questionnaires for early screening in Chia, a
      town near Bogota, from 2008 to 2010. METHOD: This was a cross-sectional study of
      prevalence. RESULTS: 37% of the 538 adolescents interviewed had anxiety symptoms,
      12.3% had depression symptoms and 9% presented anxiety and depression symptoms,
      males having greater prevalence for depression symptoms (6.9% cf 5.4% for
      females) but lacking statistical significance. There was a greater tendency for
      anxiety symptoms to be found in adolescents attending public schools. Concerning
      co morbidity, more anxiety symptoms were found in adolescents having depression
      symptoms. CONCLUSIONS: It was concluded that anxiety and depression symptoms are
      real at this age, this being reason enough why it is necessary to suspect and
      detect them on time so that adolescents can receive suitable attention.
      Protective factors must be strengthened for this to happen and there must be real
      awareness by everybody to create educational and health programmes directed
      towards ensuring good mental health.

PMID- 22634992
TI  - Influenza A (H1N1) was not associated with obesity in pregnant women living in
      Toluca, Mexico.
AB  - OBJECTIVE: The aim was to verify whether being overweight could have played a
      critical role in cases of mortality caused by influenza A (H1N1) in pregnant
      women. This virus' prevalence was also analyzed among people suffering from acute
      respiratory disease being attended at the state of Mexico's Autonomous
      University's medical research centre. METHODS: The clinical files of women having
      influenza A (H1N1) attending the Monica Pretelini maternal-perinatal hospital's
      (HMPMP) intensive care unit in Toluca, Mexico, were reviewed. According to
      international recommendations, clinical detection of possible new cases of this
      disease was kept an open as a second step. RESULTS: Five women suffering
      influenza A (H1N1) was attended at HMPMP's intensive care unit during 2009; only
      one survived. No differences in body mass index were found when comparing the
      anthropometric characteristics to another group of women affected by acute
      respiratory diseases; in fact, this parameter was below the limits for being
      overweight in both cases. No new case of influenza A (H1N1) was found after the
      first eight months of 2010. DISCUSSION: It could not be verified whether being
      overweight was a factor of higher mortality due to influenza A (H1N1) amongst
      pregnant women in the state of Mexico. The key to better survival for pregnant
      women hospitalized with influenza A (H1N1) seemed to be early treatment with
      oseltamivir. The cases decreased dramatically after the severe wave of the new
      pandemic due to unknown reasons.

PMID- 22634994
TI  - [Direct costs of complicated chicken pox in a Colombian pediatric population].
AB  - OBJECTIVE: Estimating the cost of chicken pox in a Colombian pediatric
      population. METHODOLOGY: This was a retrospective case study which searched for
      all diagnosed chicken pox cases in the Napoleon Franco Pareja children's hospital
      (Cartagena, Colombia), during 2005-2008. The hospital's records/perspective was
      used. Cost related to health personnel, lab, diagnostic images and drugs were
      searched. The micro-costing was made at Colombian peso prices for 2010. An
      adjustment was made for inflation. RESULTS: Mean hospital costs were $ 898,766
      (Q1: $ 197,348; Q3: $ 1,195,262). Mean hospital cost per day was $ 221,777 (Q1: $
      97,027; Q3: $ 293,740). Mean cost <1 year-old patients was $ 980,742 (Q1: $
      905,708; Q3: $ 1,026,031). Mean cost was $ 105,833 in 5-12 year-old patients (Q1:
      $ 39,568; Q3: $ 891,824). CONCLUSIONS: The results were similar to those of
      previous studies (in Panama and some developed countries) highlighting relatively
      high illness costs in Colombia. These results increase the evidence in favor of
      vaccination and invite Colombian public health officials to consider introducing
      a chicken pox vaccine into Colombia.

PMID- 22634995
TI  - [Perception of risk arising from atmospheric emissions from an open solid-waste
      disposal site].
AB  - OBJECTIVE: Identifying social factors determining the perception of risk in a
      population exposed to atmospheric emissions from a solid waste final disposal
      site in the city of Cali, Colombia (Basurero de Navarro--BN). METHODS: This was a
      quantitative study; a stratified sample of 199 people were surveyed, distributed
      according to socio-economic level. RESULTS: The main problem for 73% of the
      respondents was insecurity and 50% considered this to be air pollution.
      Respondents described pollution manifesting itself as pain in the throat and
      burning eyes; 64% who had lived longer in the sector believed that pollution was
      more concentrated in other parts of the city and did not affect their sector.
      83.4% believed that the BN produced pollution and associated it with the air
      (42%). 48% rated the pollution caused by the BN as being severe and 29% as being
      very serious. DISCUSSION: Risk perception was associated with the length of
      residence in the sector and individuals' age. Many gaps in information and the
      need to implement outreach programmes were highlighted. It is important that the
      community become better informed about the risks of pollution caused by the BN
      and what mitigation measures can be taken.

PMID- 22634996
TI  - [The quality of life for people suffering from complex wounds in Cartagena,
      Colombia].
AB  - OBJECTIVE: Estimating the health-related quality of life (HRQOL) of people
      suffering complex wounds who were receiving care in an extramural health service
      provider institution in Cartagena during May-June 2010. MATERIALS AND METHODS:
      This was a quantitative, descriptive study where the population/sample consisted
      of 93 adults receiving care in an extramural health service provider
      institution's complex wounds program in the city of Cartagena. A questionnaire
      regarding socio-demographic characteristics, an observational guide on the
      characteristics of injuries and the Multicultural Quality of Life Index were
      used. SPSS 12.0 software was used for the statistical analysis. RESULTS: Mean age
      was 59.3 years, females predominated (61.3%), 43.0% were married, 38.7% were
      housewives, 38.7% had finished primary education, 68.8% came from socioeconomic
      levels 2 and 3 and 93.5% of the participants had health social security
      affiliation. Complex wounds were characterised by a greater percentage being in
      the proliferative phase of healing (80.6%), measuring six to ten inches (63.4%)
      no infection being reported (85%), no amputation (90.3%) or wound-related pain
      (52.7%) and presenting physical limitations related to the wound (66.7%).
      CONCLUSIONS: People perceived their HRQOL as poor, their low scores highlighting
      low personal fulfillment, occupational functioning and physical and psychological
      wellbeing.

PMID- 22634997
TI  - [The microbiological quality of food sent to a public health laboratory in 2009].
AB  - OBJECTIVE: Testing the microbiological quality of food samples from
      municipalities in the Santander department which were processed by the Public
      Health Laboratory(PHL) in 2009. MATERIALS AND METHODS: The microbiological
      quality of food samples sent to the Santander PHL in 2009 was analysed by
      collecting reports issued by the institution and conducting a statistical
      analysis of 763 food samples from 76 municipalities in the department. Minitab
      statistical software (version 15) and Statistica (version 8.0) were used for
      analysing the information by municipality; this information was organised by food
      category and adverse incident frequency was analysed in each municipality from
      January to December 2009. RESULTS: It was seen that 45.2% (n=345) of 763 food
      records had bacterial contamination; there was a greater frequency of these
      events in the municipalities of Barichara, Barrancabermeja, Floridablanca, Giron,
      Socorro and Valle de San Jose accounting for 33.6% (n=116) of all affected
      samples. The main foods that had non-standard parameters were prepared foods (160
      samples submitted), of which 80 had alterations in quality (50%), followed by
      drinks like fruit juice and soft drinks (48.3%), dairy products (47.9%) and meat
      (40.7%). CONCLUSIONS: A high rate of food contamination was found in the samples
      sent to PHL during 2009; this information is useful for planning preventative
      action within the ongoing PHL surveillance programme.

PMID- 22634998
TI  - [Doctors and nurses' training for the early detection of the breast cancer in
      Mexico].
AB  - OBJECTIVE: Analyzing formal knowledge about breast cancer (BC) issues that
      medical and nursing students receive from different syllabuses and courses during
      their undergraduate studies. MATERIALS AND METHODS: This exploratory study was
      conducted in 2009; it was based on semi-structured interviews applied to key
      stakeholders and complemented by an analysis of their undergraduate courses. The
      study population consisted of 199 Faculties and Schools of Medicine and 108
      Schools and Colleges of Nursing and the unit of analysis consisted of the
      syllabuses for the undergraduate courses. RESULTS: 16.8% of the medical courses
      and 6.3% of the nursing courses had specific information about BC. Medical
      students predominantly received their training in biomedical and clinical areas
      and the socio-medical area to a lesser extent. The issues in nursing courses was
      mainly focused (in community areas) on promoting health and preventing disease
      (healthy lifestyles and recognition of women at high risk regarding BC).
      DISCUSSION: Little evidence was found that medicine and nursing syllabuses
      contain issues related to BC. Medical and nursing curricula should be
      strengthened to improve professional skills and abilities related to BC to solve
      the affected population's problems and health needs, particularly regarding
      primary and secondary prevention.

PMID- 22634999
TI  - [Glycosylated haemoglobin A1c compared to fasting plasma glucose in outpatients
      referred to a medical laboratory].
AB  - OBJECTIVE: Comparing haemoglobin A glycosylate (HbA1c) at different cutoff points
      for blood glucose measurement to the fasting plasma glucose (FPG) test in
      outpatients visiting a medical laboratory in the city of Medellin between March
      and April 2010. METHODS: 1,016 blood samples were studied from patients who had
      been referred to a medical laboratory. Agreement was obtained between tests
      (Kappa index); sensitivity and specificity were calculated. Different cutoff
      points for the HbA1c test were also evaluated with the ROC curve. Spearman
      correlation was used to establish association between FPG and Hb A1c. RESULTS:
      Average HbA1c was 5.7%+/-0.8 and average FPG was 96 mg/dL+/-26.1; this was higher
      in men (99.04+/-32.7). 75.4% of the samples came within the normal range for
      diagnosing diabetes with the FPG test, compared to 51.4% with the HbA1c test. The
      cutoff point where combined sensitivity and specificity presented the best HbA1c
      value in this study group was 6.2%. DISCUSSION: The HbA1c test had high
      sensitivity and specificity values, so its routine use in diagnosing diabetes
      mellitus could contribute towards active and early detection of cases to ensure
      better control of risk factors.

PMID- 22635000
TI  - [The prevalence of Demodex folliculorum infection in patients attending a general
      ophthalmological consultation].
AB  - OBJECTIVES: Determining Demodex folliculorum infection prevalence in patients
      attending general ophthalmological consultation and such infection's association
      with blepharitis. METHODS: This was a descriptive study of such prevalence. 128
      subjects who attended the Virgilio Galvis Eye Centre were randomly selected and
      the presence of D. folliculorum was determined in 4 eyelashes taken from each of
      them. RESULTS: D. folliculorum infection prevalence was 42.1% (n=54); blepharitis
      was diagnosed in 38.3% of the patients (n=49) and 63.2% of them (n=31) were
      positive for D. folliculorum. Only 29.2% of the individuals in the group without
      blepharitis (n=79) had mites (n=23) (p=0.0003). A higher number of parasites was
      found in patients with blepharitis (12.7 parasitic load index cf 5.1; p=0.0001);
      25% (n=32) of the participants had scaling in the form of cylinders and 96.9% of
      these had the mites (n=31), whereas the mite was only present in 24% (n=23) of
      subjects who had no cylinder-type scaling (n=96). CONCLUSIONS: Demodex
      folliculorum is a parasite found in people without ocular lesions; however, it is
      more frequent and has a higher parasite burden in patients with blepharitis. Our
      results suggested the need for investigating the presence of D. folliculorum in
      all patients suffering from blepharitis, especially in cases where cylinder-type
      scaling has been observed in their eyelashes.

PMID- 22635001
TI  - [Hypothyroidism prevalence and its relationship to high levels of thyroid
      peroxidase antibodies and urinary iodine in a population aged 35 and over from
      Armenia, 2009-2010].
AB  - OBJECTIVES: Determining the prevalence of hypothyroidism and its
      interrelationship with peroxidase antibodies and high urinary iodine levels as a
      means for devising a set of recommendations for health authorities regarding the
      consumption of iodised salt and the early detection of thyroid disease. METHODS:
      437 people in the municipality of Armenia (Quindio) participated in the study.
      ELISA tests were performed for free thyroxine, thyroid-stimulating hormone and
      thyroid peroxidase antibodies; a photocolorimetric analysis was carried out to
      determine urinary iodine levels. RESULTS: Hypothyroidism prevalence was 18.5%.
      Thyroid peroxidase antibodies were positive in 28.9% of the study population,
      with significantly higher prevalence amongst those with levels > 10 mIU/mL
      thyroid-stimulating hormone compared to 5.1 to 10 mIU/mL in those without it (OR
      3.2) and smokers (O.R 3,4). Free thyroxine was normal in 98.2% of participants (>
      5 mIU/mL thyroid-stimulating hormone levels) and 92% in those in whom > 10 mIU/mL
      thyroid-stimulating hormone levels were found. The average iodine level was
      565.1; levels above 300 ug/L were obtained in 81.8% of the participants.
      CONCLUSIONS: Increased positive thyroid peroxidase antibody prevalence with
      increasing thyroid-stimulating hormone values could demonstrate a high risk of
      developing autoimmune hypothyroidism in Armenia; despite high iodine levels, a
      relationship with thyroid peroxidase antibodies or thyroid-stimulating hormone
      levels could not be established.

PMID- 22635002
TI  - [Epidemiological profile of dental occlusion in children attending school in
      Envigado, Colombia].
AB  - OBJECTIVES: Ideal occlusion is a hypothetical standard based on teeth's
      morphological relationships and is characterised by perfection in anatomy and
      dental position, mesiodistal contacts, arch alignment and dental interdigitation.
      This investigation was aimed at determining the epidemiological profile of dental
      occlusion of children attending urban and rural public schools in Envigado during
      the first semester, 2010. MATERIALS AND METHODS: A cross-sectional, prospective,
      descriptive epidemiological study was carried out on patients ranging from 5 to
      12 years of age. A sample size of 436 students from 6 rural schools 6 urban
      institutions was calculated. The oral cavity was clinically examined and
      different occlusal variables on the three planes of space were evaluated:
      sagittal, transversal, and vertical. RESULTS: 436 subjects were evaluated;
      average age was 8 years (+/-1.9). The most prevalent malocclusion for permanent
      dentition was Angle's Class I (49.7%, 176/354), followed by Angle's Class II
      (43.5%, 154/354) and Angle's Class III (6.8%, 24/354). CONCLUSION: Angle's Class
      I malocclusion was the most prevalent condition with alterations in both vertical
      and transversal planes and space problems in the anterior segment.

PMID- 22635003
TI  - [HIV incidence in cases of tuberculosis in Armenia, Colombia].
AB  - Tuberculosis (TB) and the acquired immune deficiency syndrome (AIDS) are closely
      related diseases because TB is considered one of the opportunistic diseases for
      AIDS. When investigating the resurgence of TB it is very important
      epidemiologically to take into account the influence of AIDS prevalence on TB.
      This paper develops a procedure establishing HIV prevalence in TB for people in
      Armenia, Quindio, by using a mathematical model. This was done by building two
      deterministic models and relating them through a linear transfer function model.
      To parameters involved in these models had to be estimated to relate them; a
      technique was then built from unbiased estimators of minimum variance and
      secondary information for the parameters of each disease, taking into account the
      town's Secretariat of Health's secondary information. The model for Armenia led
      to concluding that tuberculosis resulted from people who had suffered from
      tuberculosis 4 periods (trimesters) ago and those sick from AIDS 2 periods ago,
      including the present. The procedure described in this work was seen to be
      applicable to the pathologies to which it is related.

PMID- 22635004
TI  - [An approach to the theoretical construction of healthcare promotion].
AB  - Definitions of healthcare promotion were examined from the theory of knowledge
      regarding its ontological and epistemological aspects as considered by several
      paradigms. Three-phase periodisation was used. The first distancing regarding the
      positivist paradigm and healthcare promotion through definitions of public health
      was made during the background phase (1920-1973). The promotion of healthcare
      acquired its own identity and became explicit policy in the midst of scenarios
      involving the confluence of paradigms during the foundational phase (1974-1986).
      Positivist and non-positivist paradigms became broadly articulated during the
      consolidation phase (1987-2008), becoming extended to methodological aspects.

PMID- 22635006
TI  - Development of a new hydrogen peroxide-based vaccine platform.
AB  - Safe and effective vaccines are crucial for maintaining public health and
      reducing the global burden of infectious disease. Here we introduce a new vaccine
      platform that uses hydrogen peroxide (H(2)O(2)) to inactivate viruses for vaccine
      production. H(2)O(2) rapidly inactivates both RNA and DNA viruses with minimal
      damage to antigenic structure or immunogenicity and is a highly effective method
      when compared with conventional vaccine inactivation approaches such as
      formaldehyde or beta-propiolactone. Mice immunized with H(2)O(2)-inactivated
      lymphocytic choriomeningitis virus (LCMV) generated cytolytic, multifunctional
      virus-specific CD8(+) T cells that conferred protection against chronic LCMV
      infection. Likewise, mice vaccinated with H(2)O(2)-inactivated vaccinia virus or
      H(2)O(2)-inactivated West Nile virus showed high virus-specific neutralizing
      antibody titers and were fully protected against lethal challenge. Together,
      these studies demonstrate that H(2)O(2)-based vaccines are highly immunogenic,
      provide protection against a range of viral pathogens in mice and represent a
      promising new approach to future vaccine development.

PMID- 22635005
TI  - Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic
      phenotype through MET.
AB  - Tumor-derived exosomes are emerging mediators of tumorigenesis. We explored the
      function of melanoma-derived exosomes in the formation of primary tumors and
      metastases in mice and human subjects. Exosomes from highly metastatic melanomas
      increased the metastatic behavior of primary tumors by permanently 'educating'
      bone marrow progenitors through the receptor tyrosine kinase MET. Melanoma
      derived exosomes also induced vascular leakiness at pre-metastatic sites and
      reprogrammed bone marrow progenitors toward a pro-vasculogenic phenotype that was
      positive for c-Kit, the receptor tyrosine kinase Tie2 and Met. Reducing Met
      expression in exosomes diminished the pro-metastatic behavior of bone marrow
      cells. Notably, MET expression was elevated in circulating CD45(-)C
      KIT(low/+)TIE2(+) bone marrow progenitors from individuals with metastatic
      melanoma. RAB1A, RAB5B, RAB7 and RAB27A, regulators of membrane trafficking and
      exosome formation, were highly expressed in melanoma cells. Rab27A RNA
      interference decreased exosome production, preventing bone marrow education and
      reducing, tumor growth and metastasis. In addition, we identified an exosome
      specific melanoma signature with prognostic and therapeutic potential comprised
      of TYRP2, VLA-4, HSP70, an HSP90 isoform and the MET oncoprotein. Our data show
      that exosome production, transfer and education of bone marrow cells supports
      tumor growth and metastasis, has prognostic value and offers promise for new
      therapeutic directions in the metastatic process.

PMID- 22635008
TI  - Structural change from homogenous structure to staging in benzoic acid
      intercalated LDH: experimental and molecular dynamics simulation insights.
AB  - The intercalation the of 4,4'-oxybis(benzoic acid) anion (OBA(2-)) into MgAl
      layered double hydroxide (LDH) was carried out in formamide, and the structural
      change of the nanocomposites from homogenous to staging was investigated through
      in situ XRD, FT-IR, TG-DSC, SEM and molecular dynamics (MD) simulations. In both
      formamide and water, the nanocomposites had a homogenous structure with a basal
      spacing of ~1.7 nm, showing the configuration of OBA(2-) was vertical to the LDH
      layers; however, with a decrease in water content after drying, the structure
      changed to a staging with a basal spacing of 2.62 nm. This resulted from the 1.72
      nm phase and another one of 0.85 nm, which was produced by the configuration of
      OBA(2-) horizontal to the LDH layers. MD simulations revealed that the LDH layers
      distorted surrounding OBA(2-), and the deformation became more severe with
      decreasing water content in the interlayer, leading to the staging formation. The
      simulated XRD pattern confirmed that the staging observed in the experimental
      pattern was of the Daumas-Herold type.

PMID- 22635007
TI  - The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi's
      sarcoma-associated herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's
      sarcoma(1), a highly vascularized tumor originating from lymphatic endothelial
      cells, and of at least two different B cell malignancies(2,3). A dimeric complex
      formed by the envelope glycoproteins H and L (gH-gL) is required for entry of
      herpesviruses into host cells(4). We show that the ephrin receptor tyrosine
      kinase A2 (EphA2) is a cellular receptor for KSHV gH-gL. EphA2 co-precipitated
      with both gH-gL and KSHV virions. Infection of human epithelial cells with a GFP
      expressing recombinant KSHV strain, as measured by FACS analysis, was increased
      upon overexpression of EphA2. Antibodies against EphA(2) and siRNAs directed
      against EphA2 inhibited infection of endothelial cells. Pretreatment of KSHV with
      soluble EphA2 resulted in inhibition of KSHV infection by up to 90%. This marked
      reduction of KSHV infection was seen with all the different epithelial and
      endothelial cells used in this study. Similarly, pretreating epithelial or
      endothelial cells with the soluble EphA2 ligand ephrinA4 impaired KSHV infection.
      Deletion of the gene encoding EphA2 essentially abolished KSHV infection of mouse
      endothelial cells. Binding of gH-gL to EphA2 triggered EphA2 phosphorylation and
      endocytosis, a major pathway of KSHV entry(5,6). Quantitative RT-PCR and in situ
      histochemistry revealed a close correlation between KSHV infection and EphA2
      expression both in cultured cells derived from human Kaposi's sarcoma lesions or
      unaffected human lymphatic endothelium, and in situ in Kaposi's sarcoma
      specimens, respectively. Taken together, our results identify EphA2, a tyrosine
      kinase with known functions in neovascularization and oncogenesis, as an entry
      receptor for KSHV.

PMID- 22635009
TI  - Gender differences during mechanical circulatory support.
AB  - Long-term mechanical circulatory support (MCS) with ventricular assist devices
      (VADs) is now an acceptable option for patients with end-stage heart failure
      (HF). There are growing numbers of reports identifying sex-related differences in
      the development and prognosis of HF and cardiac surgery. With the experience of
      1,607 VAD implantations in our institution we are the first to analyze our data
      to determine gender distribution in our patient populations and the effect of
      gender on outcomes. Of the total 1,456 patients with MCS, 1,225 were male and 231
      female. The patients were divided into three age groups-below 13 years (group 1,
      n = 100), between 13 and 50 years (group 2, n = 540) and older than 50 years
      (group 3, n = 824). Five-year survival, HF etiology, and procedural success,
      defined as 30-day and 5-year survival were analyzed retrospectively. In group 1
      the gender distribution was equal; the leading HF etiology was dilated
      cardiomyopathy (DCMP) with 17% in male (n = 17) and 19% in female (n = 19)
      patients, followed by congenital diseases (13% in male versus 9% in female) and
      postcardiotomy failure (13% in male versus 8% in female). No differences were
      seen in 5-year survival and procedural success. In group 2, significantly more
      men (n = 451, p < 0.0001) were supported by VADs. DCMP was the major cause for
      VAD implantation (54%) and was significantly more frequent in men (57.6%, p =
      <0.0001). Male patients were older (mean age = 37.1 years, p < 0.0001), with a
      longer median support time (151.6 days, p < 0.0001) and a higher median weight
      (78.2 kg, p < 0.0001). No difference was seen in procedural success whereas 5
      year survival was better in men than in women (53% vs. 42%, p = 0.02).Group 3
      consisted of 723 male patients and 101 female patients (p < 0.0001). Ischemic
      cardiomyopathy was the main HF etiology (37.9 %) and it was significantly more
      often the reason for left ventricular assist device support in men (p = 0.009).
      No differences were seen in procedural success; 5-year survival showed a better
      outcome in men (49% vs. 25%, p = 0.026). In patients supported by a VAD, gender
      has a significant impact on the distribution of diagnoses in the adult
      population. Women were underrepresented in the age group 13-50 years, and 50
      years and older, and women had a higher risk for mortality on VAD support in the
      adult age groups (groups 2 and 3).

PMID- 22635010
TI  - Control strategies for afterload reduction with an artificial vasculature device.
AB  - Ventricular assist devices (VADs) have been used successfully as a bridge to
      transplant in heart failure patients by unloading ventricular volume and
      restoring the circulation. An artificial vasculature device (AVD) is being
      developed that may better facilitate myocardial recovery than VAD by controlling
      the afterload experienced by the native heart and controlling the pulsatile
      energy entering into the arterial system from the device, potentially
      reconditioning the arterial system properties. The AVD is a valveless, 80 ml
      blood chamber with a servo-controlled pusher plate connected to the ascending
      aorta by a vascular graft. Control algorithms for the AVD were developed to
      maintain any user-defined systemic input impedance (IM) including resistance,
      elastance, and inertial components. Computer simulation and mock circulation
      models of the cardiovascular system were used to test the efficacy of two control
      strategies for the AVD: 1) average impedance position control (AIPC)-to maintain
      an average value of resistance during left ventricular (LV) systole and 2)
      instantaneous impedance force feedback (IIFF) and position control (IIPC)-to
      maintain a desired value or profile of resistance and compliance. Computer
      simulations and mock loop tests were performed to predict resulting
      cardiovascular pressures, volumes, flows, and the resistance and compliance
      experienced by the native LV during ejection for simulated normal, failing, and
      recovering LV. These results indicate that the LV volume and pressure decreased,
      and the LV stroke volume increased with decreasing IM, resulting in an increased
      ejection fraction. Although the AIPC algorithm is more stable and can tolerate
      higher levels of sensor errors and noise, the IIFF and IIPC control algorithms
      are better suited to maintain any instantaneous IM or an IM profile. The
      developed AVD impedance control algorithms may be implemented with current VADs
      to promote myocardial recovery and facilitate weaning.

PMID- 22635011
TI  - Accidental cannulation of the left ascending lumbar vein through femoral access
      still often unrecognized.
AB  - The femoral vein approach is considered to be a quick and safe route for venous
      access. However, severe complications can occur with this access because of
      misplacement. Our report describes the malposition of a large-bore dialysis
      catheter into the left ascending lumbar vein, which led to less effective
      hemodiafiltration. Clinicians should be aware of possible misplacement while
      inserting a femoral vein catheter, especially on the left side. In some cases,
      the correct position in the inferior vena cava needs confirmation before using
      the catheter.

PMID- 22635012
TI  - Evaluation of Eulerian and Lagrangian models for hemolysis estimation.
AB  - Hemolysis caused by flow-induced mechanical damage to red blood cells is still a
      problem in medical devices such as ventricular assist devices (VADs), artificial
      lungs, and mechanical heart valves. A number of different models have been
      proposed by different research groups for calculating the hemolysis, and of
      these, the power law-based models (HI(%)=Ct(alpha)tau(beta)) have proved the most
      popular because of their ease of use and applicability to a wide range of
      devices. However, within this power law category of models there are a number of
      different implementations. The aim of this work was to evaluate different power
      law-based models by calculating hemolysis in a specifically designed shearing
      device and a clinical VAD, and comparing the estimated results with experimental
      measurements of the hemolysis in these two devices. Both the Eulerian scalar
      transport and all the Lagrangian models had fairly large percentage of errors
      compared with the experiments (minimum Eulerian 91% and minimum Lagrangian 57%)
      showing they could not accurately predict the magnitude of the hemolysis.
      However, the Eulerian approach had large correlation coefficients (>0.99) showing
      that this method can predict relative hemolysis, which would be useful in
      comparative analysis, for example, for ranking different devices or for design
      optimization studies.

PMID- 22635013
TI  - Diagnosis and treatment in anhidrotic ectodermal dysplasia with immunodeficiency.
AB  - Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is characterized
      according to its various manifestations, which include ectodermal dysplasia,
      vascular anomalies, osteopetrosis, and diverse immunological abnormalities such
      as susceptibility to pathogens, impaired antibody responses to polysaccharides,
      hypogammaglobulinemia, hyper-IgM syndrome, impaired natural killer cell
      cytotoxicity, and autoimmune diseases. Two genes responsible for EDA-ID have been
      identified: nuclear factor-kappaB (NF-kappaB) essential modulator (NEMO) for X
      linked EDA-ID (XL-EDA-ID) and IkappaBalpha for autosomal-dominant EDA-ID (AD-EDA
      ID). Both genes are involved in NF-kappaB activation, such that mutations or
      related defects cause impaired NF-kappaB signaling. In particular, NEMO mutations
      are scattered across the entire NEMO gene in XL-EDA-ID patients, which explains
      the broad spectrum of clinical manifestations and the difficulties associated
      with making a diagnosis. In this review, we focus on the pathophysiology of EDA
      ID and different diagnostic strategies, which will be beneficial for early
      diagnosis and appropriate treatment.

PMID- 22635014
TI  - Osteoporosis management in post-menopausal women.
AB  - Osteoporosis is most prevalent in women over the age of 50 as the hormonal
      influence of estrogen on bone health dissipates with the onset of menopause. The
      progressive changes in bone structure, quality and density lead to pathological
      fractures and an increase in morbidity and mortality among menopausal women. This
      review will examine the 2010 North American Menopause Society (NAMS) position
      statement and other recent publications to summarize the data and combinations of
      therapies used to treat women 50 years or older with osteoporosis. To review the
      latest research and guidelines for osteoporosis management we performed a PubMed
      search using the parameters Linked to free full text, Humans, Female, Review,
      English, Middle Age (45-64 years and 45+ years), Age 65+ years, and published in
      the last five years. Articles were sorted by relevance and hand searching of
      these articles was done to further increase the yield. While a perfect treatment
      has yet to be discovered to completely cure this progressive disease, many
      breakthroughs have been made in order to prevent fractures and improve quality of
      life. Calcium and vitamin D supplementation are recommended for patients
      undergoing pharmacological treatment, however, trials looking at their
      effectiveness have mixed findings. Bisphosphonates are considered the first line
      therapy in the treatment of osteoporosis and reduce vertebral fractures by 40% to
      70% and non-vertebral fractures by 20% to 35%. Calcitonin showed promise during
      early trials in 2000 with a 33% reduction in fractures but these results have not
      been replicated and this therapy is now relegated to a second line treatment.
      Teriparatide is recommended for patients with severe osteoporosis and has been
      shown to reduce vertebral fractures 65% and non-vertebral fractures 53%.
      Selective estrogen receptor modulators (SERMs) are another useful therapy
      resulting in a 55% reduction in vertebral fractures without any documented
      advantage when looking at non-vertebral fractures. The currently available SERMs
      for this indication include raloxifene, available in the USA, and bazedoxifene,
      in Europe. Estrogen is effective, with a 27% reduction in fractures, but often is
      reserved for concomitant use for other menopausal symptoms or in patients
      intolerant of other available osteoporosis therapies. The newly approved
      monoclonal antibody for osteoporosis treatment in postmenopausal women,
      denosumab, leads to a 68% and 19% reduction of vertebral and non-vertebral
      fractures, respectively. In conclusion, the 2010 NAMS position statement provides
      an excellent framework to discuss treatment options with patients. Lifestyle
      optimization should be the bedrock of any good treatment approach. When
      pharmacological intervention is warranted, many good therapies are available
      which have been shown to reduce the risk of fractures in osteoporotic patients.
      Any treatment plan, however, will be ineffective if the patient is not compliant.
      Therefore, a detailed discussion regarding each therapeutic intervention should
      ensue, including its usefulness and side effects.

PMID- 22635015
TI  - HT and SERMs in the long-term management of osteoporosis.
AB  - Hormone therapy (HT) remains the treatment of choice for climacteric symptoms and
      for prevention and treatment of bone loss at least within ten years
      postmenopause. The usually prescribed HT doses have decreased during the past few
      years, and use of low-dose HT is becoming more popular, possibly decreasing the
      occurrence of unwanted side effects seen with conventional doses. HT has a
      fracture-reducing potential even at doses lower than usually recommended, but the
      positive effect of HT on bone disappears relatively soon after stopping HT. The
      fear of long-term side effects of HT, such as breast cancer, coronary heart
      disease (CHD) and thromboembolic events, has increased the demand to evaluate the
      role of alternative osteoporosis and fracture prevention medication in ageing
      women. The rapid worldwide decrease of HT use may increase the incidence of
      fractures if there are no compensative measures. Women who discontinue HT should
      be advised about rapid bone loss after HT, and given other potential treatment
      options. Intensive research into alternative approaches to deliver estrogenic
      activity to bone with no adverse effects on other tissues by using low doses of
      estrogen, selective estrogen receptor modulators (SERMs), or combinations of the
      two are ongoing. However, development of an ideal SERM has proved to be
      difficult, and individualization of bone-protective therapy is a remarkable
      challenge for professionals treating postmenopausal women.

PMID- 22635016
TI  - Hormone replacement therapy or SERMS in the long term treatment of osteoporosis.
AB  - Replacement therapy with estrogen and progestogen (HT) or estrogen alone (ET) and
      selective estrogen receptor modulators (SERMS) still constitute valuable
      additions to the range of osteoporosis treatments available. Due to the diverse
      action on a wide variety of organs, HT/ET has the capacity to improve quality of
      life in most postmenopausal women,- more than other more specific osteoporosis
      treatments. The initial optimism associated with HRT 20-30 years ago was reduced
      considerably after the HT arm of WHI was stopped prematurely due to safety
      concerns. Later analyses of the WHI study have, however, tempered the negative
      messages emerging from the first publication in 2002. HT/ET still constitutes a
      first line choice for prevention of bone loss and fracture in the early
      postmenopausal period for a period of 5 years. However, in women with low risk of
      adverse events classically associated with HT/ET newer analyses show that
      treatment can be continued with an acceptable risk benefit ratio. These analyses
      have also highlighted the negative impact of progestogens on breast cancer risk
      an adverse effects on the cardiovascular system. Newer guidelines therefore
      suggest that a combination of a progestogen IUD and transdermal estrogen seems to
      be the best alternative for long term treatment. This combination minimizes
      cardiovascular safety concerns by avoiding the negative impact of first pass
      metabolism in the liver seen with oral compounds and minimizes exposure to
      progestogens. SERMS are valuable alternatives, particularly in osteopenic women
      (t-score -1,0 to -2,5) at increased risk of breast cancer, but their general lack
      of anti fracture efficacy towards non vertebral fractures limits their use in
      women at high risk of osteoporotic fracture.

PMID- 22635017
TI  - Hormone therapy for management of menopausal symptoms: understanding [corrected]
      breast cancer risk.
AB  - Since the publication of the Women's Health Initiative, women seeking relief from
      menopausal symptoms often express concerns about the risk of hormone therapy
      (HT). In women at increased risk for breast cancer or with a personal history of
      breast cancer, the decision to use HT for the treatment of menopausal symptoms
      must be carefully considered in the context of the most recent literature. It is
      well established that HT is the most effective treatment for climacteric symptoms
      and sexual dysfunction. The evidence to date on the use of HT in women with a
      history of breast cancer is complicated by the fact that the majority of breast
      cancers are estrogen responsive and the concern about risk of recurrence. Over
      the past decade, survival after breast cancer treatment has continued to improve
      resulting in millions of survivors worldwide. As a result of breast cancer
      therapies, the prevalence of menopausal symptoms is increasing in survivors, and
      both clinicians and patients are seeking safe and effective therapies for symptom
      management. This article will review the role of HT in the treatment of
      menopausal symptoms in women without breast cancer and those with a personal
      history of breast cancer or those who are at increased risk of breast cancer.
      Management of menopause-related symptoms will be reviewed with a focus on
      strategies to improve quality of life.

PMID- 22635018
TI  - The role of EHP-30 as specific instrument to assess the quality of life of
      Italian women with endometriosis.
AB  - AIM: Our goals were to assess the psychometrical characteristics of EHP-30, to
      test its higher degree of appropriateness compared to the generic Quality of Life
      assessment tools for Italian women suffering from endometriosis, and to determine
      its ability to identify the disease's effects on the patients' psychosocial
      condition, highlighting critical points that can be modified for future
      linguistic validation. METHODS: Participants to our study were 98 women between
      19 and 51-year-old (M=34.4, SD=7.5), selected from patients of the Department of
      Obstetrics and Gynecology, ARNAS Civico Hospital, Palermo, Italy. All of them had
      a surgical diagnosis of endometriosis with histological confirmation. Quality of
      Life was assessed through generic (SF-36) and specific (EHP-30) instruments.
      RESULTS: Our study shows that the current Italian version of EHP-30 is affected
      by overall weaker construct validity than the English one; it seems that this has
      to be ascribed to the inadequacy of the EHP-30 translation into Italian. In
      particular, unsatisfactory reliability levels have been observed for social
      support and self-image scales. An incorrect order of response categories has been
      in addition found out for several items of the Italian version of EHP-30.
      Research results suggest solutions to adopt for a revision of the EHP-30 Italian
      version that can satisfy the requirements of validity and reliability.
      CONCLUSION: Although requiring a structural and linguistic revision, also the
      Italian version of a specific measurement instrument as EHP-30 is, appears to be
      more appropriate than generic tools to assess the quality of life of Italian
      women suffering for endometriosis.

PMID- 22635019
TI  - [Assessment of the modification of the clinical, endocrinal and metabolical
      profile of patients with PCOS syndrome treated with myo-inositol].
AB  - AIM: Aim of the study was to evaluate the effects of 24 weeks administration of
      myo-inositol plus folic acid (Inofert (r)) on clinical, endocrine and metabolic
      parameters of polycystic ovary syndrome (PCOS) patients. METHODS: Seventy women,
      18 to 35 years, were enrolled; 35 patients were enrolled as study group and
      treated with Inofert (r) (200 ug folic acid plus myo-inositol 2 g per day) for 24
      weeks. The other 35 patients, similar at baseline to patients in the study group,
      were enrolled as control group and received no treatment. In all patients the
      restoration of ovulation and variations of the endocrine and metabolic profile
      after treatment were assessed. RESULTS: After 24 weeks, only five of 35 patients
      treated with Inofert(r) and 14 of 35 patients in the control group remained
      anovulatory and this difference was statistically significant. Body mass index
      decreased significantly in the study group, while a non-significant increasing
      was recorded in the control group. Moreover, non-significant reduction in
      circulating levels of LDL, and a statistically significant increase in the levels
      of HDL in the study group were observed. CONCLUSION: Treatment with Inofert(r)
      allows to restore rapidly spontaneous ovulation in amenorrheic patients with PCOS
      and shows a significant advantage in terms of reduction in BMI and a positive
      trend in terms of changes in serum lipid profile.

PMID- 22635020
TI  - [Bacterial vaginosis prophylaxis with a vaginal device releasing chlorhexidine.
      Preliminary study].
AB  - AIM: Assessment of clinical, microbiological and subjective postmenstrual data
      relating to bacterial vaginosis in patients using a vaginal device releasing
      chlorhexidine. METHODS: Twenty women with vaginosis signs and symptoms before
      menstruation were randomized to use vaginal tampons releasing chlorhexidine or
      neutral tampons (placebo). They were reassessed after menstruation. RESULTS:
      After treatment there was improvement of symptoms referred, but not significant.
      Itching was particularly reduced after use of chlorhexidine tampon. Vaginal pH
      was reduced but not significantly in the treated group. Gram stain microscopy
      showed absence of normal vaginal microflora in all recruited patients. Frequency
      detection of Doderlein Lactobacilli and clue cells<20% at control time was
      significantly increased (70%) in patients exposed to the action of chlorhexidine
      when compared to placebo group (30%). CONCLUSION: Therapy effectiveness is
      probably due to local anti-inflammatory and antiseptic chlorhexidine properties.
      Good patient compliance is an additional result in favor of the product. Data
      collected in this study are a preliminary result.

PMID- 22635021
TI  - Comparison of the effects of letrozole and clomiphene citrate for ovulation
      induction in infertile women with polycystic ovary syndrome.
AB  - AIM: Ovulation dysfunction is one of the most common causes of reproductive
      failure in infertile couples. The prevalence of this disorder in infertile women
      is about 30 to 40%. Polycystic ovary syndrome is a common disease that is closely
      related to ovulation dysfunction and 7% of women of childbearing age are
      afflicted with it. Ovulation induction is a way to treat infertility in PCOS
      which is possible through medication or surgery. This study was conducted to
      compare the effects of Letrozole and Clomiphene citrate for ovulation induction
      in women with PCOS. METHODS: This intervention is a clinical trial study carried
      out on 100 infertile women with polycystic ovary syndrome who were referred to
      gynecologist's office and Oslian hospital. The subjects were randomly divided in
      to two groups including 50 patients who received letrozole and Clomiphene
      Citrate. Abdominal ultrasound was performed on the day 14 of the menstrual cycle
      to monitor the number and size of developed follicles and endometrial
      thickness.%age of ovulation was compared between the two groups receiving
      medication with chi2 test and t-test was used to compare the average number and
      size of follicles and endometrial thickness. Twenty-three cases (46%) in group
      receiving clomiphene citrate had thin endometrium and thin endometrium was
      observed in 1 case (2%) of group receiving letrozole. Among 50 subjects who
      received clomiphene citrate, 10 people (20%) reported blurred vision, 9 patients
      (18%) headache, 6 patients (12%) nausea and 2 patients (4%) reported vomiting and
      one (2%) twin pregnancies was observed, but no complications were reported in
      group receiving letrozole. RESULTS: Mean age, parity, and the duration of
      infertility were similar in all patients. Ovulation rate was 88%; similar in both
      groups. The average number of follicles in the group receiving clomiphene citrate
      was 58/1+/-32/2 and in the group receiving letrezole it was 50/0+/-30/1. Average
      follicle size in both groups was almost similar. Endometrial thickness in the
      group receiving letrezole was 27/1+/-71/9 and in the group receiving clomiphene
      citrate it was 06/3+/-08/6. Pregnancy rate in both groups was almost similar.
      CONCLUSION: This study showed that stimulation of letrozole and clomiphene
      citrate on ovulation and was almost the same and clomiphene citrate caused
      endometrial thinning more often than letrozole. Also the side effects reported by
      patients in the group receiving clomiphene citrate were higher, while in the
      group receiving letrozole no complication was reported. Based on these findings
      letrozole can be considered an appropriate alternative for clomiphene citrate
      without side effects.

PMID- 22635022
TI  - As part of our efforts to monitor the progress made by the International Journal
      of Gynecological Cancer. Introduction.

PMID- 22635023
TI  - From the tailoring of adjuvant treatment to the tailoring of pelvic and aortic
      lymphadenectomy in stage I endometrial cancer.

PMID- 22635024
TI  - Genome-wide single nucleotide polymorphism arrays as a diagnostic tool in
      patients with synchronous endometrial and ovarian cancer.
AB  - OBJECTIVE: Synchronous carcinomas in the endometrium and ovaries can be a single
      primary tumor with metastasis (SPM) or dual primary tumors (DP). Although the
      prognosis of DP without any metastases is significantly better than that of SPM,
      pathological diagnosis is difficult in tumors with similar histological features.
      MATERIALS AND METHODS: In 10 tumors from 5 patients with synchronous endometrial
      and ovarian carcinomas, 250K single nucleotide polymorphism arrays were
      performed. The patients were genetically diagnosed according to the pattern of
      copy number alterations (CNAs), in addition to microsatellite status and
      mutational analysis of PIK3CA, PTEN, K-Ras, and CTNNB1. RESULTS: Of the 5
      patients, 3 exhibited identical CNA patterns, including type, loci, and degree of
      each alteration in the endometrial and ovarian carcinomas. The other 2 exhibited
      CNAs only in either endometrial or ovarian carcinoma. All 5 tumors had 1 or more
      genetic mutations in the genes examined. One patient exhibited mutations both in
      PIK3CA and PTEN at discordant sites between endometrial and ovarian carcinomas,
      whereas the other 4 exhibited concordant mutations. Overall, 4 of the 5 patients
      were genetically diagnosed with SPM, and the remaining 1 with DP. The
      pathological diagnosis was not in agreement with the genetic diagnosis in 4 of
      the 5 patients. CONCLUSIONS: Genome-wide genotyping diagnosis may represent a
      useful approach for distinguishing between SPM and DP in synchronous endometrial
      and ovarian carcinomas.

PMID- 22635025
TI  - Not all fat is equal: differential gene expression and potential therapeutic
      targets in subcutaneous adipose, visceral adipose, and endometrium of obese women
      with and without endometrial cancer.
AB  - OBJECTIVE: To identify obesity-related cancer genes in endometrial and adipose
      tissue depots of body mass index-matched morbidly obese women with and without
      endometrial cancer. METHODS: Eight women undergoing hysterectomy (4 women with
      and 4 women without endometrial cancer) were matched by age (52.6 years) and body
      mass index (44.5 kg/m). Endometrium, visceral adipose tissue, and subcutaneous
      adipose tissue were collected and subjected to microarray analysis using
      Affymetrix Human Genome U133 Plus 2.0 Arrays. Gene set enrichment analysis used
      to extract biological information from the gene expression data and t test metric
      ranked and compared genes in the expression data set. Protein expression was
      measured in the endometrial samples, and serum was collected for
      hormone/metabolite assays. RESULTS: No significant differences were detected in
      hormone/metabolite levels between groups. Gene set enrichment analysis
      comparisons demonstrated that endometrial, visceral adipose and subcutaneous
      adipose tissues displayed 40, 47, and 38 alternatively regulated gene set
      pathways when comparing patients with and without cancer. Nineteen gene sets were
      alternately regulated in both visceral and subcutaneous adipose tissues; however,
      eighteen of these were regulated in the opposite direction. Five pathways were
      significantly and alternately regulated in all 3 tissue types and included
      glycolysis/gluconeogenesis, ribosome, peroxisome proliferator activated receptor
      signaling, pathogenic Escherichia coli infection, and natural killer-mediated
      cytotoxicity. In the malignant endometrium, liver kinase B1 underexpression was
      observed in all patients with cancer. Liver kinase B1 underexpression decreased
      adenosine monophosphate-activated protein kinase activity toward acetyl-CoA
      carboxylase and implied enhanced lipid biosynthesis in obesity-induced
      endometrial cancer. CONCLUSIONS: Subcutaneous and visceral adipose tissue depots
      have opposite patterns of gene expression in obese patients with and without
      endometrial cancer. The altered de novo lipogenesis and individual gene targets
      identified provide new potential targets for cancer treatment and prevention for
      at-risk obese women.

PMID- 22635026
TI  - Role of chromosome 3q26 gain in predicting progression of cervical dysplasia.
AB  - OBJECTIVE: This study aimed to determine whether 3q26 gain can predict which low
      grade squamous intraepithelial lesions (LSILs) and atypical squamous cells of
      undetermined significance (ASCUSs) will progress to higher-grade squamous
      intraepithelial lesion (HSIL). METHODS: Liquid cytology specimens of LSIL and
      ASCUS from 73 women were examined using fluorescent in situ hybridization (FISH)
      for the detection of 3q26 gain. All women underwent colposcopy and biopsy at the
      initial visit and 40 of them with histology showing cervical intraepithelial
      neoplasia 1 (CIN 1) or human papillomavirus infection (koilocytosis) were
      included in the study. They were reevaluated with liquid cytology, colposcopy,
      and biopsy after a median follow-up of 17.5 months. RESULTS: A total of 40 cases
      were analyzed (31 LSILs and 9 ASCUSs). Of these cases, 8 (20%; 6 LSILs and 2
      ASCUSs) were positive and 32 (80%) were negative for 3q26 gain according to FISH.
      Three of the 8 positive women (38%) progressed to HSIL/CIN 2 or worse, whereas
      none of the 32 negative women did so. 3q26 gain could predict progression with a
      negative predictive value of 100% (95% confidence interval, 89.1%-100%). In
      addition, women positive for 3q26 gain had a significantly lower regression rate
      compared with negative women (P = 0.009). CONCLUSIONS: In this first prospective
      study, 3q26 gain in LSIL/ASCUS cytology exhibited an impressive negative
      predictive value for progression to HSIL/CIN 2 or worse. Thus, 3q26 gain may be
      useful in stratifying patients' risk for progression and possibly alter
      management and reduce cost of follow-up.

PMID- 22635027
TI  - BRCA1 is expressed in uterine serous carcinoma (USC) and controls insulin-like
      growth factor I receptor (IGF-IR) gene expression in USC cell lines.
AB  - OBJECTIVE: The insulin-like growth factor I receptor (IGF-IR) and BRCA1 affect
      cell growth and apoptosis. Little information is available about BRCA1 activity
      on the IGF signaling pathway. This study evaluated the effect of BRCA1 on IGF-IR
      expression. METHODS: BRCA1 and IGF-IR immunohistochemistry on archival tissues
      (35 uterine serous carcinomas [USCs] and 17 metastases) were performed. USPC1 and
      USPC2 cell lines were transiently cotransfected with an IGF-IR promoter construct
      driving a luciferase reporter gene and a BRCA1 expression plasmid. Endogenous IGF
      IR levels were evaluated by Western immunoblotting. RESULTS: We found high BRCA1
      and IGF-IR protein expression in primary and metastatic USC tumors. All samples
      were immunostained for BRCA1-71% strongly stained; and 33/35 (94%) were stained
      positive for IGF-IR-2 (6%) strongly stained. No difference in BRCA1 and IGF-IR
      staining intensity was noted between BRCA1/2 mutation carriers and noncarriers.
      Metastatic tumors stained more intensely for BRCA1 than did the primary tumor
      site (P = 0.041) and with borderline significance for IGF-IR (P = 0.069). BRCA1
      and IGF-IR staining did not correlate to survival. BRCA1 expression led to 35%
      and 54% reduction in IGF-IR promoter activity in the USPC1 and USCP2 cell lines,
      respectively. Western immunoblotting showed a decline in phosphorylated IGF-IR
      and phosphorylated AKT in both transiently and stably transfected cells.
      CONCLUSIONS: BRCA1 and IGF-IR are highly expressed in USC tumors. BRCA1
      suppresses IGF-IR gene expression and activity. These findings suggest a possible
      biological link between the BRCA1 and the IGF-I signaling pathways in USC. The
      clinical implications of this association need to be explored.

PMID- 22635028
TI  - Silencing Wnt2B by siRNA interference inhibits metastasis and enhances
      chemotherapy sensitivity in ovarian cancer.
AB  - OBJECTIVE: Wnt2B overexpression is thought to be involved in tumor progression
      through the activation of the canonical Wingless and INT-1 signaling pathway.
      However, the mechanism of Wnt2B signaling in oncogenesis is unknown. In this
      study, we investigated whether silencing Wnt2B expression could inhibit the
      invasiveness of ovarian cancer cells and reduce drug resistance.
      METHODS/MATERIALS: Four ovarian carcinoma cell lines, SKOV3, OV2008, A2780, and
      C13K, were used. Protein levels were studied by Western blotting. The colony
      formation ability and invasive ability were determined through colony formation
      assay and the Matrigel transwell assay, respectively. Cell viability was
      determined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
      assay, whereas apoptosis was assessed using flow cytometry analysis. RESULTS:
      Among the 4 ovarian carcinoma cell lines, the A2780 cells and C13K cells
      expressed Wnt2B, and these 2 cell lines were used for analyzing the mechanism of
      Wnt2B. The down-regulation of Wnt2B inhibited cell colony formation and
      invasiveness. Enhanced paclitaxel or cisplatin sensitivity was observed in A2780
      cells or C13K cells treated with Wnt2B siRNA, respectively. In the presence of
      Wnt2B siRNA treatment, the caspase-9/B-cell lymphoma 2 (BCL2)/B-cell lymphoma-xL
      (BCL-xL) pathway and the epithelial-mesenchymal transition/phosphorylated protein
      kinase B pathway were inhibited. CONCLUSION: These data suggest that Wnt2B indeed
      plays an important role in ovarian cancer metastasis and drug resistance. This
      study may provide a new therapeutic target for and a better understanding of
      ovarian cancer therapy.

PMID- 22635029
TI  - An open-label phase 2 study of twice-weekly bortezomib and intermittent pegylated
      liposomal doxorubicin in patients with ovarian cancer failing platinum-containing
      regimens.
AB  - BACKGROUND: Pegylated liposomal doxorubicin (PLD) is an established treatment for
      relapsed ovarian cancer. Preclinical and clinical evidences in other tumor types
      suggest that the proteasome inhibitor bortezomib can act synergistically with
      PLD. METHODS: Patients with relapsed ovarian cancer (N = 58), previously treated
      with platinum (100%) and taxane (95%), received bortezomib, 1.3 mg/m intravenous
      (days 1, 4, 8, and 11), and PLD, 30 mg/m intravenous (day 1), every 3 weeks.
      Tumor responses were assessed using Response Evaluation Criteria In Solid Tumors
      and Gynecologic Cancer Intergroup criteria. An optimal 2-stage design was
      implemented. Gene expression profiling in peripheral blood was characterized
      before and during treatment in 10 platinum-sensitive patients enrolled in stage 2
      of the study. RESULTS: Median number of bortezomib-PLD cycles was 3.5. Of 38
      patients in the platinum-sensitive group, 9 responses were observed (median
      duration, 4.8 months). The platinum-resistant group was closed at stage 1 owing
      to lack of response. Toxicity was moderate and mainly consisted of hematologic,
      gastrointestinal, and mucositis events. Of the total 58 patients, peripheral
      neuropathy was reported in 9 patients (none were grade 3). Transcription
      profiling identified the prevalence of genes associated with ribonucleoprotein
      complexes, RNA processing, and protein translation. The gene expression changes
      were more robust in patients who responded or had stable disease compared with
      patients who had progressive disease. CONCLUSIONS: The combination of bortezomib
      and PLD was well tolerated, but the antitumor activity is insufficient to warrant
      further investigation in ovarian cancer.

PMID- 22635030
TI  - Gemcitabine for advanced endometrial cancer: a retrospective study of the
      Memorial sloan-Kettering Cancer Center experience.
AB  - BACKGROUND: Gemcitabine is active in several gynecologic malignancies including
      ovarian cancer, cervical cancer, and uterine leiomyosarcoma. It has been used in
      an off-label setting for the treatment of advanced endometrial cancer, despite
      lack of published data showing efficacy. We performed a retrospective study to
      determine the progression-free survival and response rate of endometrial cancer
      patients treated with gemcitabine at Memorial Sloan-Kettering Cancer Center.
      METHODS: Eligible patients had histologically confirmed advanced (stage IV or
      recurrent) endometrial cancer that was treated with single-agent gemcitabine at
      Memorial Sloan-Kettering Cancer Center between 1999 and 2009. Response to therapy
      was determined by review of computed tomography imaging by Response Evaluation
      Criteria in Solid Tumors 1.1 criteria. RESULTS: Forty-six patients were included
      in the analysis. Median age was 66 years (range, 52-87 years). All patients were
      previously treated with chemotherapy. The median number of prior lines of
      chemotherapy was 2 (range, 1-8). Median dose of gemcitabine administered was 800
      mg/m infused on days 1 and 8 of a 21-day cycle. Predominant histology was
      endometrioid (48%, n = 22) followed by serous (35%, n = 16), clear cell (15%, n =
      7), and undifferentiated (2%, n = 1). Overall response rate was 10.9% (95%
      confidence interval, 1.9%-19.9%); 5 patients (11%) achieved a partial response.
      Thirteen patients (28%) displayed stable disease lasting at least 3 months. Of
      note, 5 (71%) of the 7 patients with clear cell histology displayed stable
      disease or partial response (n = 5). The median progression-free survival was 3.0
      months (95% confidence interval, 2.1-3.3 months). Nonhematologic grades 3 and 4
      toxicities were rare. Ten patients (22%) were treated with granulocyte colony
      stimulating factor during treatment. Grade 3 thrombocytopenia was seen in 4
      patients (9%). There were no cases of grade 4 thrombocytopenia. CONCLUSIONS: In a
      mixed population of patients with previously treated advanced endometrial cancer,
      gemcitabine was well tolerated and showed modest activity. Patients with clear
      cell histology appeared to have greater likelihood of benefit.

PMID- 22635031
TI  - Case-case study of factors associated to hMLH1, hMSH2, and hMSH6 protein
      expression among endometrial cancer patients of the University District Hospital
      of San Juan, Puerto Rico.
AB  - Lynch syndrome (LS) is an autosomal dominant disorder caused by DNA mismatch
      repair (MMR) system deficiencies. Women affected by LS present a 40% to 60%
      lifetime risk of endometrial cancer (EC). OBJECTIVE: This case-case study aims to
      determine the frequency of the hMLH1, hMSH2, and hMSH6 MMR proteins and the
      factors (age, family history of cancer [FHC] related to LS, and body mass index
      [BMI]) associated to their absence in EC patients attending the University
      District Hospital of San Juan, Puerto Rico. MATERIALS AND METHODS: Twenty cases
      were preliminary evaluated for the MMR protein expression by immunohistochemistry
      testing and classified as positive cases (presence of protein) or negative cases
      (absence of protein). The statistical analysis was based on the logistic
      regression model using the maximum likelihood estimation (MLE). The Bayesian
      approach was used to determine the posterior probability (posterior Pr[odds ratio
      {OR} > 1]). RESULTS: Results showed absence for at least 1 MMR protein in 25% of
      the cases, 15% for hMLH1, and 10% for hMSH2. None of the cases showed an absence
      for hMSH6. The MLE demonstrated that women diagnosed with EC before the age of 50
      (OR: 12.4; 95% confidence interval [CI] = 0.5-322.7), having FHC related to LS
      (OR: 17.7; 95% CI = 0.6-534.6), and having lower BMI (OR: 2.38; 95% CI = 0.39
      14.28) present higher odds than their counterparts of lacking an MMR protein,
      once adjusted for potential predictors (P > 0.05). The posterior probability that
      an excess risk of lacking an MMR protein occurs was 95% or greater for each
      predictor. CONCLUSIONS: Our study in this Hispanic population supports previous
      studies in that younger age, FHC, and lower BMI are associated with increased
      odds of having an absence of MMR protein expression. Further studies with larger
      sample sizes should be performed.

PMID- 22635032
TI  - Cervical cancer incidence in French Guiana: South American.
AB  - For the first time, the incidence of cervical cancer was estimated in French
      Guiana, an overseas French Territory of South America. A certified cancer
      registry collected exhaustive data on cervical cancer between 2003 and 2005. The
      age-standardized rate of invasive cervical cancer was 30.3 per 100,000 women.
      Women from rural areas had lesions with a significantly greater extension than
      women from urban areas. Compared to South American figures, the standardized
      incidence of cervical cancer seemed relatively high when viewed in comparison
      with the gross domestic product per capita. The curative orientation of the
      health system should move from opportunistic screening for cervical cancer to
      organized screening, with an emphasis on the rural parts of French Guiana.

PMID- 22635033
TI  - EP-EMA regimen (etoposide and cisplatin with etoposide, methotrexate, and
      dactinomycin) in a series of 18 women with gestational trophoblastic neoplasia.
AB  - OBJECTIVE: Evaluation of toxicity and outcome of high-risk gestational
      trophoblastic neoplasia when treated with EP-EMA (etoposide, 150 mg/m; cisplatin,
      75 mg/m, intravenous, day 1; etoposide, 100 mg/m; methotrexate, 300 mg/m;
      dactinomycin, 0.5 mg, intravenous, day 8, every two weeks). MATERIALS AND
      METHODS: We conducted a retrospective chart review of the period 2004-2010. The
      first-line chemotherapy regimen for high-risk gestational tropholdastic neoplasia
      was EP-EMA. RESULTS: Eighteen patients were treated with EP-EMA, either as first
      line chemotherapy for high-risk gestational trophoblastic neoplasia (n = 6),
      placental site trophoblastic tumor (n = 1), or as salvage chemotherapy for
      gestational trophoblastic neoplasia after single-agent methotrexate
      (methotrexate, 1 mg/kg, on days 1, 3, 5, and 7 every two weeks) (n = 10) or high
      dose methotrexate-etoposide: methotrexate, 1000 mg/m, on day 1; etoposide, 100
      mg/m, on days 1 to 2, every week) (n = 1). Median number of cycles of EP-EMA was
      8 (range, 3-11). Median follow-up was 19 months (range, 7-77 months). Concerning
      response rate, 16 patients (89%) achieved complete remission without disease
      recurrence.Two patients (11%) died: One patient with placental site trophoblastic
      tumor died of progressive disease; the second patient presented with
      choriocarcinoma, primarily metastasized to liver, lung, skin, kidney, and brain.
      She died of sepsis and endocarditis after adding intrathecal methotrexate and
      switching cisplatin to carboplatin in the EP-EMA regimen. Toxicity was
      significant. Eight treatment changes were made owing to grade 2 to grade 3
      ototoxicity: 7 to high-dose methotrexate-etoposide, 1 change of cisplatin to
      carboplatin. Fifteen patients (83%) experienced grade 3/4 neutropenia.

PMID- 22635034
TI  - Relevance of psychosocial factors at work for workers' health.

PMID- 22635035
TI  - Validation of the questionnaire on hand function assessment in leprosy.
AB  - OBJECTIVE: To validate the psychometric properties of the questionnaire on hand
      function assessment in leprosy. METHODS: Study conducted with a convenience
      sample of 101 consecutive patients in Brasilia (Central-Western Brazil), from
      June 2008 to July 2009. The individuals were adults affected by leprosy, with
      impairment of the ulnar, median and radial nerves. Interobservers and
      intraobserver reproducibility was analyzed through successive interviews, and
      construct validity was analyzed through association between age, clinical form of
      leprosy, duration of nerve injury, grip and pinch strength measured with a
      dynamometer, sensibility test performed with Semmes-Weinstein monofilaments and
      manual ability assessment using the Jebsen test of hand function. Pondered kappa
      coefficient was calculated and a Bland-Altman plot was constructed to assess the
      reproducibility of the instrument. For internal consistency, Cronbach's alpha
      coefficient was utilized. Pearson's correlation coefficient was calculated and a
      multiple regression model was used. RESULTS: The pondered kappa values for
      interobservers and intraobserver assessments ranged from 0.86 to 0.97 and from
      0.85 to 0.97, respectively. The value of Cronbach's alpha coefficient was 0.967.
      Pearson's correlation coefficient showed an association (p < 0.001) among
      duration of nerve injury, grip and pinch strength, cutaneous sensibility and mean
      score in the Jebsen Test. The mean score of the questionnaire on hand functional
      assessment in leprosy was associated with operational classification of leprosy,
      duration of nerve injury, grip strength, cutaneous sensibility and manual ability
      (p < 0.0001 for the model as a whole). CONCLUSIONS: The questionnaire on hand
      functional assessment in leprosy presents almost perfect interobservers and
      intraobserver reproducibility, high internal consistency and correlation with
      operational classification of leprosy, duration of nerve injury, grip strength,
      cutaneous sensibility in the hands and manual ability.

PMID- 22635036
TI  - Incidence of congenital syphilis in Brazil and its relationship with the Family
      Health Strategy.
AB  - OBJECTIVE: To estimate the incidence of congenital syphilis and identify its
      relationship with Family Health Strategy coverage. METHODS: An observational
      ecological study was carried out with both descriptive and analytical components,
      by two different approaches: one that explores a temporal series (2003 to 2008)
      and one that focuses on the 2008 data. The secondary data (epidemiological,
      demographic, and socioeconomic) were obtained from the Department of Informatics
      of the Unified Health System and the Brazilian Institute of Geography and
      Statistics. Analysis of the possible effects of the implementation of the Family
      Health Strategy on the prevention of congenital syphilis was performed on
      selected subgroups of counties according to two approaches: a) the variation of
      the average annual rate of incidence of congenital syphilis in different strata
      of Family Health Program coverage between 2003 and 2008 and the calculation of
      the simple linear regression coefficient; and b) a negative binomial regression
      analysis of data from 2008 to control for confounding factors. RESULTS:
      Increasingly trends of congenital syphilis notification in Brazil reflect social
      inequalities in the distribution of cases. The incidence of congenital syphilis
      was lower in the counties with high Family Health Strategy coverage; however,
      after controlling for the co-variables, such an effect might be attributed to the
      coverage of prenatal care and the demographic characteristics of the counties
      where the implementation of the Strategy was a priority. CONCLUSIONS: Despite the
      increase in prenatal care coverage, the actions implemented still exhibit low
      effectiveness in the prevention of congenital syphilis. Prenatal care performed
      by Family Health Strategy teams did not control syphilis better than the prenatal
      care performed within the context of other models of assistance.

PMID- 22635037
TI  - Factors associated to medicine use among children from the 2004 Pelotas Birth
      Cohort (Brazil).
AB  - OBJECTIVE: To identify factors associated to medicine use among children from the
      2004 Pelotas Birth Cohort, Brazil. METHODS: Prospective study to evaluate
      medicine use in children aged 3, 12 and 24 months regardless of the reasons,
      therapeutic indication or class. The study included 3,985 children followed up at
      three months of age, 3,907 at 12 months, and 3,868 at the last follow-up time of
      24 months. Mothers were interviewed to collect information on medicine use during
      the recall period of 15 days prior to the interview. The outcome was studied
      according to sociodemographic and perinatal variables, mother's perception of
      child's health and breastfeeding status. Crude and adjusted analyses were
      performed by Poisson regression following a hierarchical model. RESULTS: The
      prevalence of medicine use ranged from 55% to 65% in the three follow-ups. After
      controlling for confounders, some variables remained associated to medicine use
      only at the three-month follow-up with greatest use among children of younger
      mothers, those children who had intrapartum complications, low birthweight, were
      never breastfed and were admitted to a hospital. Greatest medicine use was also
      associated with being a firstborn child at 3 and 12 months; mother's perception
      of their child health as fair or poor and children whose mothers have private
      health insurance at 12 and 24 months; highest maternal education level at all
      follow-up times. CONCLUSIONS: Different variables influence medicine use among
      children during the first two years of life and they change as the child ages
      especially maternal factors and those associated to the child's health problems.

PMID- 22635038
TI  - Regular use of dental services among adults and older adults in a vulnerable
      region in Southern Brazil.
AB  - OBJECTIVE: To estimate the prevalence of regular use of dental care services by
      adults and older adults residing in vulnerable community and to identify
      associated factors. METHODS: A population-based cross-sectional study was carried
      out with 3,391 adults and older adults residing in areas of social vulnerability
      in Porto Alegre, Southern Brazil, from July to December of 2009. A systematic
      sampling method was used the selection probability proportional to the population
      of each of the the 121 census sectors. The outcome for regular use of dental care
      services was defined as regular use of dental services, regardless of the
      presence of dental problems. A standardized questionnaire was administered, which
      included demographic, socioeconomic, type of dental care services, self
      perception of dental health and self-perceived needs variables. A chi-square test
      for heterogeneity was used for bivariate analyses, and a Poisson regression with
      a robust variance and Wald tests were performed for the adjusted analysis.
      RESULTS: The prevalence of regular use of dental services was 25.7%. The
      prevalence was higher among people with >12 years schooling (PR 2.48
      [95%CI:1.96;3.15]), higher income (PR 1.95[95%CI: 1.03;1.53]), use of private
      health services (PR 1.43 [95%CI: 1.20;1.71]),excellent self-perceived oral health
      (PR 4.44 [95%CI: 3.07;6.42]) and a self-perceived need for consultation related
      to routine checkup (RP 2.13 [95%CI: 1.54;2.96]). CONCLUSIONS: Inequalities were
      found in the regular use of dental services. Integrated approaches that raise
      awareness of oral health, improve self-care and expand access to dental services,
      may contribute to increase the use of dental services on a regular basis.

PMID- 22635039
TI  - Healthcare regulatory concepts in Brazil.
AB  - The healthcare regulatory concepts used in Brazilian scientific publications on
      healthcare management were reviewed. A typo-logical classification for regulatory
      concepts was developed from the most current ideas in five disciplines: life
      sciences, law, economics, sociology and political science. Four ideas stood out:
      control, balance, adaptation and direction, with greatest emphasis on the
      technical nature of regulation. The political nature of regulation was secondary.
      It was considered that dis-cussion of healthcare regulatory concepts was
      connected with comprehension of the role that the state plays in this sector. De
      finition of the forms of state intervention is the key convergence point between
      the different ways of conceptualizing healthcare regulation.

PMID- 22635041
TI  - High intergrain critical current density in fine-grain (Ba0.6K0.4)Fe2As2 wires
      and bulks.
AB  - The K- and Co-doped BaFe(2)As(2) (Ba-122) superconducting compounds are
      potentially useful for applications because they have upper critical fields
      (H(c2)) of well over 50 T, H(c2) anisotropy gamma < 2and thin-film critical
      current densities J(c) exceeding 1 MA cm(-2) (refs 1-4) at 4.2 K. However, thin
      film bicrystals of Co-doped Ba-122 clearly exhibit weak link behaviour for [001]
      tilt misorientations of more than about 5 degrees , suggesting that textured
      substrates would be needed for applications, as in the cuprates. Here we present
      a contrary and very much more positive result in which untextured polycrystalline
      (Ba(0.6)K(0.4))Fe(2)As(2) bulks and round wires with high grain boundary density
      have transport critical current densities well over 0.1 MA cm(-2) (self-field,
      4.2 K), more than 10 times higher than that of any other round untextured
      ferropnictide wire and 4-5 times higher than the best textured flat wire. The
      enhanced grain connectivity is ascribed to their much improved phase purity and
      to the enhanced vortex stiffness of this low-anisotropy compound (gamma~1-2) when
      compared with YBa(2)Cu(3)O(7-x) (gamma~5).

PMID- 22635042
TI  - Extracellular-matrix tethering regulates stem-cell fate.
AB  - To investigate how substrate properties influence stem-cell fate, we cultured
      single human epidermal stem cells on polydimethylsiloxane (PDMS) and
      polyacrylamide (PAAm) hydrogel surfaces, 0.1 kPa-2.3 MPa in stiffness, with a
      covalently attached collagen coating. Cell spreading and differentiation were
      unaffected by polydimethylsiloxane stiffness. However, cells on polyacrylamide of
      low elastic modulus (0.5 kPa) could not form stable focal adhesions and
      differentiated as a result of decreased activation of the extracellular-signal
      related kinase (ERK)/mitogen-activated protein kinase (MAPK) signalling pathway.
      The differentiation of human mesenchymal stem cells was also unaffected by PDMS
      stiffness but regulated by the elastic modulus of PAAm. Dextran penetration
      measurements indicated that polyacrylamide substrates of low elastic modulus were
      more porous than stiff substrates, suggesting that the collagen anchoring points
      would be further apart. We then changed collagen crosslink concentration and used
      hydrogel-nanoparticle substrates to vary anchoring distance at constant substrate
      stiffness. Lower collagen anchoring density resulted in increased
      differentiation. We conclude that stem cells exert a mechanical force on collagen
      fibres and gauge the feedback to make cell-fate decisions.

PMID- 22635043
TI  - Plasmonic nanosensors with inverse sensitivity by means of enzyme-guided crystal
      growth.
AB  - Lowering the limit of detection is key to the design of sensors needed for food
      safety regulations, environmental policies and the diagnosis of severe diseases.
      However, because conventional transducers generate a signal that is directly
      proportional to the concentration of the target molecule, ultralow concentrations
      of the molecule result in variations in the physical properties of the sensor
      that are tiny, and therefore difficult to detect with confidence. Here we present
      a signal-generation mechanism that redefines the limit of detection of
      nanoparticle sensors by inducing a signal that is larger when the target molecule
      is less concentrated. The key step to achieve this inverse sensitivity is to use
      an enzyme that controls the rate of nucleation of silver nanocrystals on
      plasmonic transducers. We demonstrate the outstanding sensitivity and robustness
      of this approach by detecting the cancer biomarker prostate-specific antigen down
      to 10(-18) g ml(-1) (4 * 10(-20) M) in whole serum.

PMID- 22635044
TI  - Giant magnetocaloric effect driven by structural transitions.
AB  - Magnetic cooling could be a radically different energy solution substituting
      conventional vapour compression refrigeration in the future. For the largest
      cooling effects of most potential refrigerants we need to fully exploit the
      different degrees of freedom such as magnetism and crystal structure. We report
      now for Heusler-type Ni-Mn-In-(Co) magnetic shape-memory alloys, the adiabatic
      temperature change DeltaT(ad) = -3.6 to -6.2 K under a moderate field of 2 T.
      Here it is the structural transition that plays the dominant role towards the net
      cooling effect. A phenomenological model is established that reveals the
      parameters essential for such a large DeltaT(ad). We also demonstrate that
      obstacles to the application of Heusler alloys, namely the usually large
      hysteresis and limited operating temperature window, can be overcome by using the
      multi-response to different external stimuli and/or fine-tuning the lattice
      parameters, and by stacking a series of alloys with tailored magnetostructural
      transitions.

PMID- 22635045
TI  - In silico screening of carbon-capture materials.
AB  - One of the main bottlenecks to deploying large-scale carbon dioxide capture and
      storage (CCS) in power plants is the energy required to separate the CO(2) from
      flue gas. For example, near-term CCS technology applied to coal-fired power
      plants is projected to reduce the net output of the plant by some 30% and to
      increase the cost of electricity by 60-80%. Developing capture materials and
      processes that reduce the parasitic energy imposed by CCS is therefore an
      important area of research. We have developed a computational approach to rank
      adsorbents for their performance in CCS. Using this analysis, we have screened
      hundreds of thousands of zeolite and zeolitic imidazolate framework structures
      and identified many different structures that have the potential to reduce the
      parasitic energy of CCS by 30-40% compared with near-term technologies.

PMID- 22635046
TI  - Ketamine alters the neurogenesis of rat cortical neural stem progenitor cells.
AB  - OBJECTIVE: High doses or prolonged exposure to ketamine increase neuronal
      apoptosis in the developing brain, although effects on neural stem progenitor
      cells remain unexplored. This study investigated dose- and time-dependent
      responses to ketamine on cell death and neurogenesis in cultured rat fetal
      cortical neural stem progenitor cells. DESIGN: Laboratory-based study. SETTING:
      University research laboratory. SUBJECT: Sprague-Dawley rats. INTERVENTIONS:
      Neural stem progenitor cells were isolated from the cortex of Sprague-Dawley rat
      fetuses on embryonic day 17. In dose-response experiments, cultured neural stem
      progenitor cells were exposed to different concentrations of ketamine (0-100 uM)
      for 24 hrs. In time-course experiments, neural stem progenitor cells cultures
      were exposed to 10 uM ketamine for different durations (0-48 hrs). MEASUREMENTS
      AND MAIN RESULTS: Apoptosis and necrosis in neural stem progenitor cells were
      assessed using activated caspase-3 immunostaining and lactate dehydrogenase
      assays, respectively. Proliferative changes in neural stem progenitor cells were
      detected using bromo-deoxyuridine incorporation and Ki67 immunostaining. Neuronal
      differentiation was assessed using Tuj-1 immunostaining. Cultured neural stem
      progenitor cells were resistant to apoptosis and necrosis following all
      concentrations and durations of ketamine exposure tested. Ketamine inhibited
      proliferation with decreased numbers of bromo-deoxyuridine-positive cells
      following ketamine exposure to 100 uM for 24 hrs (p<.005) or 10 uM for 48 hrs (p<
      .01), and reduced numbers of Ki67-positive cells following exposure to ketamine
      concentration>10 uM for 24 hrs (p<.001) or at 10 uM for 48 hrs (p<.01). Ketamine
      enhanced neuronal differentiation, with all ketamine concentrations increasing
      Tuj-1-positive neurons (p<.001) after 24-hrs of exposure. This also occurred with
      all exposures to 10 uM ketamine for >8 hrs (p<.001). CONCLUSIONS: Clinically
      relevant concentrations of ketamine do not induce cell death in neural stem
      progenitor cells via apoptosis or necrosis. Ketamine alters the proliferation and
      increases the neuronal differentiation of neural stem progenitor cells isolated
      from the rat neocortex. These studies imply that ketamine exposure during fetal
      or neonatal life may alter neurogenesis and subsequent brain development.

PMID- 22635047
TI  - Toll-like receptor 3 plays a central role in cardiac dysfunction during
      polymicrobial sepsis.
AB  - OBJECTIVE: To determine the role of Toll-like receptor 3 in cardiac dysfunction
      during polymicrobial sepsis. DESIGN: Controlled animal study. SETTING: University
      research laboratory. SUBJECTS: Male C57BL/6, wild-type, Toll-like receptor 3-/-.
      INTERVENTION: Myocardial dysfunction is a major consequence of septic shock and
      contributes to the high mortality of sepsis. Toll-like receptors (TLRs) play a
      critical role in the pathophysiology of sepsis/septic shock. TLR3 is located in
      intracellular endosomes, and recognizes double-stranded RNA. This study examined
      the role of TLR3 in cardiac dysfunction following cecal ligation and puncture
      (CLP)-induced sepsis. TLR3 knockout (TLR3-/-, n=12) and age-matched wild-type
      (n=12) mice were subjected to CLP. Cardiac function was measured by
      echocardiography before and 6 hrs after CLP. MEASUREMENTS AND MAIN RESULTS: CLP
      resulted in significant cardiac dysfunction as evidenced by decreased ejection
      fraction by 25.7% and fractional shortening by 29.8%, respectively. However, TLR3
      /- mice showed a maintenance of cardiac function at pre-CLP levels. Wild-type
      mice showed 50% mortality at 58 hrs and 100% mortality at 154 hrs after CLP. In
      striking contrast, 70% of TLR3-/- mice survived indefinitely, that is, >200 hrs.
      TLR3 deficiency significantly decreased CLP-induced cardiac-myocyte apoptosis and
      attenuated CLP-induced Fas and Fas ligand expression in the myocardium. CLP
      activation of TLR4-mediated nuclear factor-kappaB and Toll/IL-1 receptor-domain
      containing adapter-inducing interferon-beta-dependant interferon signaling
      pathways was prevented by TLR3 deficiency. In addition, CLP-increased vascular
      cell adhesion molecule-1 and intercellular adhesion molecule-1 expression, and
      neutrophil and macrophage sequestration in the myocardium were also attenuated in
      septic TLR3-/- mice. More significantly, adoptive transfer of wild-type bone
      marrow stromal cells to TLR3-/- mice abolished the cardioprotective effect in
      sepsis. CONCLUSIONS: These data indicate that TLR3 plays a deleterious role in
      mediating cardiac dysfunction in sepsis. Thus, modulation of the TLR3 activity
      may be useful in preventing cardiac dysfunction in sepsis.

PMID- 22635048
TI  - Development and pilot testing of a decision aid for surrogates of patients with
      prolonged mechanical ventilation.
AB  - OBJECTIVE: Shared decision making is inadequate in intensive care units. Decision
      aids can improve decision making quality, though their role in an intensive care
      units setting is unclear. We aimed to develop and pilot test a decision aid for
      shared decision makers of patients undergoing prolonged mechanical ventilation.
      SETTING: Intensive care units at three medical centers. SUBJECTS: Fifty-three
      surrogate decision makers and 58 physicians. DESIGN AND INTERVENTIONS: We
      developed the decision aid using defined methodological guidelines. After an
      iterative revision process, formative cognitive testing was performed among
      surrogate-physician dyads. Next, we compared the decision aid to usual care
      control in a prospective, before/after design study. MEASUREMENTS AND MAIN
      RESULTS: Primary outcomes were physician-surrogate discordance for expected
      patient survival, comprehension of relevant medical information, and the quality
      of communication. Compared to control, the intervention group had lower surrogate
      physician discordance (7 [10] vs. 43 [21]), greater comprehension (11.4 [0.7] vs.
      6.1 [3.7]), and improved quality of communication (8.7 [1.3] vs. 8.4 [1.3]) (all
      p<.05) post-intervention. Hospital costs were lower in the intervention group
      ($110,609 vs. $178,618; p=.044); mortality did not differ by group (38% vs. 50%,
      p=.95). Ninety-four percent of the surrogates and 100% of the physicians reported
      that the decision aid was useful in decision making. CONCLUSION: We developed a
      prolonged mechanical ventilation decision aid that is feasible, acceptable, and
      associated with both improved decision-making quality and less resource
      utilization. Further evaluation using a randomized controlled trial design is
      required to evaluate the decision aid's effect on long-term patient and surrogate
      outcomes.

PMID- 22635050
TI  - An efficient 3C-silicon carbide/titania nanocomposite photoelectrode for dye
      sensitized solar cell.
AB  - Dye-sensitized solar cells (DSSCs) are fabricated using a novel 3C-SiC/TiO(2)
      nanocomposite as a photoelectrode to enhance the power conversion efficiency.
      Compared with a pristine nanocrystalline TiO(2) cell, a DSSC based on a 3C-SiC
      (0.04 wt%)/TiO(2) nanocomposite photoelectrode shows ~115% increase in power
      conversion efficiency.

PMID- 22635049
TI  - Depressive symptoms in spouses of older patients with severe sepsis.
AB  - OBJECTIVE: To examine whether spouses of patients with severe sepsis are at
      increased risk for depression independent of the spouse's presepsis history,
      whether this risk differs by sex, and is associated with a sepsis patient's
      disability after hospitalization. DESIGN: Prospective longitudinal cohort study.
      SETTING: Population-based cohort of U.S. adults over 50 yrs old interviewed as
      part of the Health and Retirement Study (1993-2008). PATIENTS: Nine hundred
      twenty-nine patient-spouse dyads comprising 1,212 hospitalizations for severe
      sepsis. MEASUREMENTS AND MAIN RESULTS: Severe sepsis was identified using a
      validated algorithm in Medicare claims. Depression was assessed with a modified
      version of the Center for Epidemiologic Studies Depression Scale. All analyses
      were stratified by gender. The prevalence of substantial depressive symptoms in
      wives of patients with severe sepsis increased by 14 percentage points at the
      time of severe sepsis (from 20% at a median of 1.1 yrs presepsis to 34% at a
      median of 1 yr postsepsis) with an odds ratio of 3.74 (95% confidence interval:
      2.20, 6.37), in multivariable regression. Husbands had an 8 percentage point
      increase in the prevalence of substantial depressive symptoms, which was not
      significant in multivariable regression (odds ratio 1.90, 95% confidence interval
      0.75, 4.71). The increase in depression was not explained by bereavement; women
      had greater odds of substantial depressive symptoms even when their spouse
      survived a severe sepsis hospitalization (odds ratio 2.86, 95% confidence
      interval 1.06, 7.73). Wives of sepsis survivors who were disabled were more
      likely to be depressed (odds ratio 1.35 per activities of daily living limitation
      of sepsis survivor, 95% confidence interval 1.12, 1.64); however, controlling for
      patient disability only slightly attenuated the association between sepsis and
      wives' depression (odds ratio 2.61, 95% confidence interval 0.93, 7.38).
      CONCLUSIONS: Older women may be at greater risk for depression if their spouse is
      hospitalized for severe sepsis. Spouses of patients with severe sepsis may
      benefit from greater support and depression screening, both when their loved one
      dies and when their loved one survives.

PMID- 22635051
TI  - An unsymmetrical lithium-ion pathway between charge and discharge processes in a
      two-phase stage of Li4Ti5O12.
AB  - In this work, we investigated lithium-ion diffusion in spinel Li(4)Ti(5)O(12)
      nano-particles with carbon coating by electrochemical impedance spectroscopy
      (EIS), and proposed a hybrid model of the unsymmetrical lithium-ion pathway
      between charge and discharge processes. In this hybrid model, the charge process
      still follows the core-shell model, but in the discharge process, the phase
      transition evolves by growth of a few nuclei on the surface. And this hybrid
      model is possibly attributed to the nonuniform electron conductivity inside the
      Li(4)Ti(5)O(12) particles. Additionally, the relaxation process and the particle
      morphology are also carefully discussed in the experiment to show that this
      hybrid model is quite practical. Thereby, this investigation presents an
      unsymmetrical lithium-ion pathway in Li(4)Ti(5)O(12) particles, which could be
      extended to other active materials in lithium ion batteries.

PMID- 22635052
TI  - The downward spiral of tau and autolysosomes: a new hypothesis in
      neurodegeneration.
AB  - A growing body of research has connected autophagy to neurodegenerative diseases
      such as Alzheimer disease (AD). In autopsied AD brain, large multivesicular
      bodies accumulate in neurons. Knockout mice deficient for key autophagy genes
      demonstrate age-dependent neurodegeneration. Most neurodegenerative diseases are
      characterized by accumulation of insoluble protein species; the type of protein
      and the location of aggregates within the nervous system help to define the type
      of disorder. It has been hypothesized that the inability to degrade such
      aggregates is a major causative factor in neuronal dysfunction and eventual
      neuronal death. As neurons are postmitotic and thus cannot regenerate themselves,
      mechanisms of protein clearance have received much attention in the field. The
      function of the ubiquitin-proteasome system (UPS) is impaired in models of
      neurodegeneration, and overexpression of chaperone proteins, such as those in the
      HSP70 family, leads to beneficial effects in many models of proteinopathies.
      Recently, studies of the effects of autophagy as a clearance mechanism have
      uncovered compelling evidence that inducing autophagy can alleviate many
      pathogenic and behavioral symptoms in animal and cellular models of
      neurodegeneration.

PMID- 22635053
TI  - Asthma at-risk registers--can be effective if carefully constructed and correctly
      implemented.

PMID- 22635054
TI  - A miniature bidirectional telemetry system for in vivo gastric slow wave
      recordings.
AB  - Stomach contractions are initiated and coordinated by an underlying electrical
      activity (slow waves), and electrical dysrhythmias accompany motility diseases.
      Electrical recordings taken directly from the stomach provide the most valuable
      data, but face technical constraints. Serosal or mucosal electrodes have cables
      that traverse the abdominal wall, or a natural orifice, causing discomfort and
      possible infection, and restricting mobility. These problems motivated the
      development of a wireless system. The bidirectional telemetric system constitutes
      a front-end transponder, a back-end receiver and a graphical userinter face. The
      front-end module conditions the analogue signals, then digitizes and loads the
      data into a radio for transmission. Data receipt at the backend is acknowledged
      via a transceiver function. The system was validated in a bench-top study, then
      validated in vivo using serosal electrodes connected simultaneously to a
      commercial wired system. The front-end module was 35 * 35 * 27 mm3 and weighed 20
      g. Bench-top tests demonstrated reliable communication within a distance range of
      30 m, power consumption of 13.5 mW, and 124 h operation when utilizing a 560 mAh,
      3 V battery. In vivo,slow wave frequencies were recorded identically with the
      wireless and wired reference systems (2.4 cycles min-1), automated activation
      time detection was modestly better for the wireless system (5% versus 14% FP
      rate), and signal amplitudes were modestly higher via the wireless system (462
      versus 3 86MUV; p<0.001). This telemetric system for slow wave acquisition is
      reliable,power efficient, readily portable and potentially implantable. The
      device will enable chronic monitoring and evaluation of slow wave patterns in
      animals and patients.0967-3334/

PMID- 22635055
TI  - Cation radii induced structural variation in fluorescent alkaline earth networks
      constructed from tautomers of a nucleobase analogue.
AB  - Nucleobase tautomers and their metal complexes have attracted considerable
      attention due to their fascinating architectures along with wide applications. In
      this paper, 4,6-dihydroxypyrimidine (H(2)DHP), an analogue of uracil and thymine,
      was employed to react with the vital elements of alkaline earth metals in an
      aqueous solution and lead to the formation of four novel complexes, [Mg(HDHP)(2)
      (H(2)O)(4)] (1), [Ca(HDHP)(2)(H(2)O)(3)](n).nH(2)O (2),
      [Sr(HDHP)(2)(H(2)O)(3)](n).nH(2)O (3), and [Ba(HDHP)(2)(H(2)O)(2)](n).nH(2)O (4),
      which have been characterized by elemental analysis, IR, TG, UV-Vis, PL, powder
      and single-crystal X-ray diffraction and progressively evolve from zero
      dimensional (0D) mononuclear, one-dimensional (1D) zig-zag double chain, two
      dimensional (2D) double layer, to a three-dimensional (3D) porous network along
      with the increase of cation radii. This tendency in dimensionality follows
      salient crystal engineering principles and can be explained by considering
      factors such as hard-soft acid-base principles and cation radii. The deprotonated
      H(2)DHP ligand exhibits four new coordination modes, namely, O-monodentate
      (complex 1), N,O-chelating (complexes 2 and 3), O,O-bridging (complexes 2 and 3),
      and kappa(1)O:kappa(2)O-bridging mode (complex 4). Interestingly, the structural
      investigation indicates that the HDHP(-) monoanion shows three unusual types of
      tautomers, which are essential for the diagnosis of disease and investigation of
      medicine. Furthermore, the four complexes exhibit strong blue emission compared
      to free H(2)DHP ligand at room temperature and may be potential candidates for
      blue fluorescent biological materials used in organisms.

PMID- 22635057
TI  - Assessing and managing metabolic syndrome and cardiovascular risk in midlife
      women.
AB  - BACKGROUND: The components of metabolic syndrome (MetS), a major cardiovascular
      risk in women that includes diabetes, hypertension, and dyslipidemia, can evolve
      during the perimenopause transition. Lifestyle interventions have been shown to
      ameliorate or prevent individual components of MetS. PURPOSE: This article will
      describe the hormonal and vascular changes occurring during perimenopause and
      discuss how they set the stage for MetS in women. The available screening tools
      (Framingham Assessment for Coronary Heart Disease vs Framingham General
      Cardiovascular Risk Profile vs Reynolds Risk Assessment) will be compared and
      contrasted within the context of the 2011 Updated Guidelines for the Prevention
      of Cardiovascular Disease in Women via case study. CONCLUSIONS AND CLINICAL
      IMPLICATIONS: Target goals and interventions to reduce or ameliorate the
      components of MetS will be presented, with a focus on achieving ideal
      cardiovascular health.

PMID- 22635056
TI  - Internalized gap junctions are degraded by autophagy.
AB  - Direct intercellular communication mediated by gap junctions (GJs) is a hallmark
      of normal cell and tissue physiology. In addition, GJs significantly contribute
      to physical cell-cell adhesion. Clearly, these cellular functions require precise
      modulation. Typically, GJs represent arrays of hundreds to thousands of densely
      packed channels, each one assembled from two half-channels (connexons), that dock
      head-on in the extracellular space to form the channel arrays that link
      neighboring cells together. Interestingly, docked GJ channels cannot be separated
      into connexons under physiological conditions, posing potential challenges to GJ
      channel renewal and physical cell-cell separation. We described previously that
      cells continuously-and effectively after treatment with natural inflammatory
      mediators-internalize their GJs in an endo-/exocytosis process that utilizes
      clathrin-mediated endocytosis components, thus enabling these critical cellular
      functions. GJ internalization generates characteristic cytoplasmic double
      membrane vesicles, described and termed earlier annular GJs (AGJs) or
      connexosomes. Here, using expression of the major fluorescent-tagged GJ protein,
      connexin 43 (Cx43-GFP/YFP/mApple) in HeLa cells, analysis of endogenously
      expressed Cx43, ultrastructural analyses, confocal colocalization microscopy,
      pharmacological and molecular biological RNAi approaches depleting cells of key
      autophagic proteins, we provide compelling evidence that GJs, following
      internalization, are degraded by autophagy. The ubiquitin-binding protein
      p62/sequestosome 1 was identified in targeting internalized GJs to autophagic
      degradation. While previous studies identified proteasomal and endo-/lysosomal
      pathways in Cx43 and GJ degradation, our study provides novel molecular and
      mechanistic insights into an alternative GJ degradation pathway. Its recent link
      to health and disease lends additional importance to this GJ degradation
      mechanism and to autophagy in general.

PMID- 22635058
TI  - Management of hyponatremia in heart failure: role of tolvaptan.
AB  - BACKGROUND: Asymptomatic or clinically mild hyponatremia commonly occurs in the
      setting of heart failure, especially among elderly and severely decompensated,
      fluid-overloaded patients, and is associated with increased morbidity and
      mortality. Successful detection and treatment of hyponatremia by cardiovascular
      and advanced practice nurses caring for patients with heart failure are part of
      multidisciplinary team care. Nurses should be able to detect signs and symptoms
      of hyponatremia and, even when patients are asymptomatic, initiate appropriate
      treatment promptly to prevent complications. PURPOSE: In this review, the
      epidemiology and pathophysiology of hyponatremia in heart failure, and signs and
      symptoms are described. In patients with heart failure, challenges involved in
      determining the type of hyponatremia (hypervolemic, hypovolemic, or euvolemic)
      and in correctly managing hyponatremia to prevent serious complications are
      presented. Conventional treatment options and their limitations are reviewed, and
      the vasopressin-receptor antagonist tolvaptan, an emerging oral therapy option,
      is introduced and discussed. CONCLUSIONS: Hyponatremia is a marker of morbidity
      and mortality in patients with heart failure. Nurses working collaboratively with
      other healthcare providers must be able to recognize the condition and understand
      treatment options, including potential adverse effects of current and emerging
      therapies. One emerging therapy--tolvaptan--can be used in hypervolemic and
      euvolemic hyponatremic patients with heart failure to correct serum sodium level
      without negatively affecting renal function. CLINICAL IMPLICATIONS: Improved
      nurse understanding of hyponatremia in patients with heart failure may promote
      nurse-initiated or nurse-facilitated detection and management, which could
      decrease mortality and morbidity.

PMID- 22635059
TI  - Living with half a heart--experiences of young adults with single ventricle
      physiology: a qualitative study.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Approximately 3% of children with congenital
      heart disease born in Denmark have single ventricle physiology (SVP). In previous
      decades, these children did not survive into adulthood. However, because of new
      surgical techniques and improved medical care, they now have a 90% survival rate.
      Several studies have described the somatic status of SVP patients using clinical
      parameters; however, only a few studies have researched the life perspectives and
      coping skills in this patient group. The aim of this study was to investigate how
      young adults with an SVP diagnosis are coping with adulthood and the emotional
      experiences of daily life. SUBJECTS AND METHODS: Semistructured, qualitative
      interviews were held with 11 SVP respondents, selected by physical and
      psychological parameters identified in an earlier quantitative study. Data from
      the interviews were analyzed by a research group using a phenomenological
      methodology. RESULTS AND CONCLUSIONS: The goal for SVP patients is to gain
      control over their disease to live normal lives. Patients require special support
      from their core network to overcome physical and psychological challenges.
      Respondents underscored the need for friends and resource persons outside the
      family to help lift them out of their role as disabled cardiac patients and
      provide them with "normal" life experiences.

PMID- 22635060
TI  - Early cognitive behavioral therapy for depression after cardiac surgery.
AB  - BACKGROUND: Despite high rates of postcardiac surgery depression, studies of
      depression treatment in this population have been limited. OBJECTIVE: The aim of
      this study was to evaluate early cognitive behavioral therapy (CBT) in a home
      environment in patients recovering from cardiac surgery. METHODS: : From July
      2006 through October 2009, we conducted a randomized controlled trial and
      enrolled 808 patients who were screened for depressive symptoms using the Beck
      Depression Inventory (BDI) in the hospital and 1 month later. Patients were
      interviewed using the Structured Clinical Interview for DSM-IV; those who met
      criteria for clinical depression (n = 81) were randomized to CBT (n = 45) or
      usual care (UC; n = 36). After completion of the UC period, 25 individuals were
      offered later CBT (UC + CBT). RESULTS: Main outcomes (depressive symptoms [BDI]
      and clinical depression [Structured Clinical Interview for DSM-IV]) were
      evaluated after 8 weeks using intention-to-treat principles and linear mixed
      models. Compared with the UC group, in the CBT group, there was greater decline
      in BDI scores (beta = 1.41; 95% confidence interval [CI], 0.81-2.02; P = < .001)
      and greater remission of clinical depression (29 [64%] vs 9 [25%]; number need to
      treat, 2.5; 95% CI, 1.7-4.9; P < .001). Compared with the early CBT group (median
      time from surgery to CBT, 45.5 days) the later UC + CBT group (median time from
      surgery to CBT, 122 days) also experienced a reduction in BDI scores, but the
      group * time effect was smaller (beta = 0.79; 95% CI, 0.10-1.47; P = .03) and
      remission rates between the 2 groups did not differ. CONCLUSIONS: Early home CBT
      is effective in depressed postcardiac surgery patients. Early treatment is
      associated with greater symptom reduction than similar therapy given later after
      surgery.

PMID- 22635061
TI  - Mobile phone interventions to increase physical activity and reduce weight: a
      systematic review.
AB  - OBJECTIVE: This systematic review was conducted to determine user satisfaction
      and effectiveness of smartphone applications and text messaging interventions to
      promote weight reduction and physical activity. METHODS: Studies of smartphone
      applications and text messaging interventions related to the cardiovascular risk
      factors of physical inactivity and overweight/obesity published between January
      2005 and August 2010 were eligible. Studies related to disease management were
      excluded. Study characteristics and results were gathered and synthesized.
      RESULTS: A total of 36 citations from CINAHL, EMBASE, MEDLINE, PsycINFO, and
      PubMed were identified; 7 articles were eligible for inclusion. The most frequent
      outcome measured in the studies was change in the weight of participants (57%).
      More than half of the studies (71%) reported statistically significant results in
      at least 1 outcome of weight loss, physical activity, dietary intake, decreased
      body mass index, decreased waist circumference, sugar-sweetened beverage intake,
      screen time, and satisfaction or acceptability outcomes. CONCLUSIONS: All of the
      technology interventions that were supported by education or an additional
      intervention demonstrated a beneficial impact of text messaging or smartphone
      application for reduction of physical inactivity and/or overweight/obesity. More
      rigorous trials that determine what parts of the technology or intervention are
      effective as well as establishment of cost-effectiveness are necessary for
      further evaluation of smartphone and text messaging interventions.

PMID- 22635062
TI  - Unsupervised modeling of cell morphology dynamics for time-lapse microscopy.
AB  - Analysis of cellular phenotypes in large imaging data sets conventionally
      involves supervised statistical methods, which require user-annotated training
      data. This paper introduces an unsupervised learning method, based on temporally
      constrained combinatorial clustering, for automatic prediction of cell morphology
      classes in time-resolved images. We applied the unsupervised method to diverse
      fluorescent markers and screening data and validated accurate classification of
      human cell phenotypes, demonstrating fully objective data labeling in image-based
      systems biology.

PMID- 22635072
TI  - Thermal-induced dynamic self-assembly of adenine-grafted polyoxometalate
      complexes.
AB  - A new kind of organic-inorganic hybrid complexes based on polyoxometalate were
      synthesized through symmetrically grafting two adeninyl groups onto Anderson-type
      MnMo(6) clusters and encapsulating the clusters by organic surfactants. The
      resultant complexes exhibited thermal-induced dynamic self-assembly behaviors
      which greatly depended on the ambient temperature and the chain length of
      cationic surfactants. With the encapsulation of a short surfactant tetrabutyl
      ammonium, the complex assembled into fibrous, rod-like, and tubular architectures
      respectively upon heating; while for the case of using a long surfactant
      dimethyldioctadecyl ammonium as counter ions, the assemblies of the complex
      transformed from fibers to spheres with the increased temperature. Moreover, the
      two types of transformations were both reversible during a cooling process. The
      related mechanism was investigated by combining multiple characterization methods
      including X-ray crystallography, XPS, FT-IR and temperature-dependent (1)H NMR,
      which indicated that such a thermal-induced morphological transformation resulted
      from a synergy effect of the variation of the multiple hydrogen bonds among the
      complexes and the rearrangement of the surfactants surrounding the MnMo(6)
      clusters. These results demonstrated a new concept that hydrogen bonds can be
      rationally employed as the driving force for the fabrication of polyoxometalate
      based materials with smart responsive properties.

PMID- 22635073
TI  - Long-lasting hypotensive effect in renal hypertensive rats induced by nitric
      oxide released from a ruthenium complex.
AB  - In this study, we investigated the effect of the ruthenium complex
      [Ru(terpy)(bdq)NO] (TERPY) on the arterial pressure from renal hypertensive 2
      kidney-1 clip (2K-1C) rats, which was compared with sodium nitroprusside (SNP).
      The most interesting finding was that the intravenous bolus injection of TERPY
      (2.5, 5.0, 7 mg/kg) had a dose-dependent hypotensive effect only in 2K-1C rats.
      On the other hand, SNP (35 and 70 MUg/kg) presented a similar hypotensive effect
      in both normotensive (2K) and 2K-1C although the effect of 70 MUg/kg was >35
      MUg/kg. The injection of the nonselective NO-synthase inhibitor N-nitro-L
      arginine methyl ester (L-NAME) increased the arterial pressure in 2K and 2K-1C
      rats with a similar magnitude. After infusion of L-NAME, the hypotensive effect
      induced by TERPY and SNP was potentiated in both 2K and in 2K-1C rats. The
      administration of the superoxide scavenger 4-hydroxy-2,2,6,6
      tetramethylpiperidine-N-oxyl increased the hypotensive effect induced by TERPY or
      SNP in both 2K and 2K-1C rats. The hypotensive effect induced by TERPY was longer
      than that produced by SNP. Taken together, our results show that the TERPY has a
      long-lasting hypotensive effect, which has a dose dependence and higher magnitude
      in 2K-1C compared with in 2K rats. In comparison with SNP, TERPY is less potent
      in inducing arterial pressure fall, but it presents a much longer hypotensive
      effect.

PMID- 22635074
TI  - Intrathecal morphine remotely preconditions the heart via a neural pathway.
AB  - Central opioid receptor activation triggers cardioprotection against ischemia
      reperfusion injury, independent of peripheral opioid receptor activity. Using a
      rodent model of myocardial ischemia reperfusion injury with infarct size as the
      primary outcome, we tested the hypothesis that spinal opioids confer this
      beneficial effect via a neural pathway. Intrathecal morphine reduced the infarct
      size compared with control (23% +/- 7% vs. 58% +/- 3%, respectively, P < 0.01).
      Prior antagonism of the autonomic pathway, and the receptors for bradykinin,
      calcitonin gene-related peptide, and the KATP channel, respectively, abolished
      this cardioprotection (54% +/- 13%, 52% +/- 10%, 56% +/- 9%, and 49% +/- 8%,
      respectively, P < 0.05). In a second set of experiments, we demonstrated that the
      increased expression of myocardial phosphorylated-Akt and endothelial nitric
      oxide synthase induced by intrathecal morphine was blocked by prior
      administration of hexamethonium. These findings support the notion that spinal
      opioid receptors stimulate a neural pathway that uses nonopioid neurotransmitters
      to confer cardioprotection from ischemia reperfusion injury. The use of
      intrathecal morphine for this purpose has potential clinical application, and it
      is already being used in the perioperative period to provide prolonged analgesia.

PMID- 22635075
TI  - Sex differences in postischemic cardiac dysfunction and norepinephrine overflow
      in rat heart: the role of estrogen against myocardial ischemia-reperfusion damage
      via an NO-mediated mechanism.
AB  - The purpose of this study is to elucidate the relationship between sex difference
      and norepinephrine (NE) release in the pathogenesis of myocardial
      ischemia/reperfusion (I/R) injury. Isolated male and female rat hearts were
      subjected to 40-minute global ischemia followed by 30-minute reperfusion.
      Compared with male hearts, I/R-induced cardiac dysfunction, such as decreased
      left ventricular developed pressure and dP/dtmax and increased left ventricular
      end diastolic pressure, was significantly attenuated in female hearts. An
      excessive NE overflow in the coronary effluent from the postischemic heart in
      females was much less than that in males. These sex differences were abolished by
      ovariectomy, but in vivo treatment with 17beta-estradiol recovered it. This
      ameliorating effect of 17beta-estradiol was not observed in the presence of
      nitric oxide (NO) synthase inhibitor N-nitro-L-arginine. When NOx (NO2/NO3)
      levels in the coronary effluent after onset of reperfusion were measured,
      reversed correlated relationships between NOx production and I/R-induced cardiac
      dysfunction, and NE overflow, were observed. These findings suggest that sex
      differences in the postischemic cardiac dysfunction are closely related to the NE
      overflow from the postischemic heart and that estrogen plays a key role in the
      cardioprotective effect against I/R injury in female rats, by suppressing NE
      release via the enhancement of NO production.

PMID- 22635076
TI  - An apoptosis signal-regulating kinase 1 inhibitor reduces cardiomyocyte apoptosis
      and infarct size in a rat ischemia-reperfusion model.
AB  - PURPOSES: We determined whether a small molecule inhibitor of apoptosis signal
      regulating kinase 1 (ASK1-i) could reduce myocardial infarct size in a rat
      ischemia/reperfusion model. METHODS AND RESULTS: Sprague-Dawley rats were
      randomized to 3 groups: ASK1-i infusion (n = 16), vehicle infusion (n = 16), or
      ischemic preconditioning (IPC; n = 15). Infusion of ASK1-i (10 mg/kg, iv) or
      vehicle commenced 45 minutes before myocardial ischemia. IPC consisted of 3
      cycles of 3 minutes of coronary occlusion followed by 5 minutes of reperfusion
      immediately before index myocardial ischemia, which consisted of 30-minute left
      coronary occlusion followed by 180 minutes of reperfusion. Pathologic analysis
      revealed no significant difference in the ischemic risk size among the 3 groups.
      ASK1-I and IPC significantly reduced myocardial infarct size (27.7% +/- 3.3%,
      16.5% +/- 3.4%, and 41.5% +/- 4.8% in the ASK1-i group, the IPC group, and the
      vehicle group, respectively; P = 0.0002) and apoptosis (the percentage of
      apoptotic nuclei averaged 11.6% +/- 1.0%, 10.2% +/- 1.7%, and 17.7% +/- 2.0% in
      the ASK1-i group, IPC group, and vehicle group, respectively, P = 0.0055).
      CONCLUSIONS: A small molecule inhibitor of ASK1 was shown for the first time to
      reduce apoptosis and myocardial infarct size in a rat model of
      ischemia/reperfusion.

PMID- 22635077
TI  - Laudatio for centenary of the birth of Luigi Di Bella, MD, PhD.
AB  - On the centennial of the birth of Luigi Di Bella, the desire to memorialise, at
      least in part, his thoughts has prompted us to write this tribute, in the hope
      that one day his dreams may come true. Throughout his research for a treatment of
      cancer, he deemed it necessary to employ a complex array of substances that, by
      acting centripetally on neoplastic cells, could in turn be capable of affecting,
      either simultaneously or sequentially, the myriad of biological reactions
      supporting their lives. Hence, not a substance but a method (Di Bella Method,
      DBM). These brief hints at some aspects of Prof. Di Bella's multifaceted
      scientific vision are aimed not only at reasserting the truth, but also at giving
      a modest contribution to a novel and free direction in experimental and clinical
      science.

PMID- 22635078
TI  - The Di Bella Method (DBM) improved survival, objective response and performance
      status in a retrospective observational clinical study on 23 tumours of the head
      and neck.
AB  - In 23 cases of carcinoma of the head and neck, the combined use of Somatostatin
      and/or its analogue Octreotide, prolactin inhibitors, Melatonin, Retinoids,
      Vitamin E, Vitamin D3, Vitamin C, Calcium, chondroitin-sulphate, and minimal oral
      doses of cyclophosphamide (50-100 mg/day) led to a decided increase in survival
      with respect to the median values reported in the literature for the same tumours
      and stages, together with an evident improvement in the quality of life, partial
      or complete objective responses and, in some cases, complete and stable cure with
      functional recovery. The rationale and the mechanisms of molecular biology of the
      treatment are discussed, showing that the treatment has a differentiating,
      apoptotic, antiproliferative, antiangiogenic and antimetastatic effect, and,
      unlike chemo- and/or radiotherapy, preserves and enhances the trophism and
      functionality of organs, tissues and immunitary and antitumoral homeostasis. This
      result, achieved without toxicity, demonstrates the efficacy of this biological
      multitherapy (Prof. Luigi Di Bella's method or DBM) and is in agreement with the
      positive results already published on the use of the DBM in various neoplastic
      diseases. We believe it is of use to report these cases to invite greater
      interest in the possibilities opened up by this biological multitherapy.

PMID- 22635079
TI  - Sertoli-Leydig cell tumor of the ovary--morphological and immunohistochemical
      analysis.
AB  - Sertoli-Leydig cell tumor is a rare and usually unilateral tumor of the ovary
      occurring in women's reproductive age. Only about 10% of these patients are over
      50 years of age. One third of these patients are suffering from signs of
      virilisation. This work summarizes the morphological and immunohistochemical
      characteristics of this tumor in a 56-year old woman with clinical signs of
      virilisation.

PMID- 22635080
TI  - Sunitinib treatment for refractory malignant pheochromocytoma.
AB  - We report the clinical response and adverse events of a female patient treated
      for recurrent malignant pheochromocytoma using the tyrosine kinase inhibitor
      sunitinib. A 41-year-old woman underwent adrenectomy and nephrectomy
      forpotentially malignant adrenal pheochromocytoma. Fifty-four months after
      surgery, abdominal computed tomography (CT) and Iodine-131
      metaiodobenzylguanidine((131)I-MIBG) scintigraphy revealed multiple tumors in the
      liver. Two chemotherapy protocols were administered in succession (first line:
      cyclophosphamide/vinblastine/dacarbazine; second line:
      cisplatin/docetaxel/ifomide). Despite these treatments, however, the tumors
      continued to progress. Treatment with sunitinib was initiated, but the patient
      quickly developed critical hypertension caused by tumor lysis syndrome. The
      sunitinib dose was reduced, and a partial response, as defined by the Response
      Evaluation Criteria in Solid Tumors (RECIST), was observed after 6 treatment
      cycles. Moreover, no severe adverse events occurred during this lower-dose
      sunitinib treatment. Unfortunately, sunitinib treatment became unaffordable for
      the patient, who eventually resorted to palliative care and died 37 months later.
      This case study is consistent with previous reports indicating that appropriate
      doses of sunitinib can induce a partial antitumor response in patients with
      refractory pheochromocytoma.

PMID- 22635081
TI  - Laparoscope resection of ectopic corticosteroid-secreting adrenal adenoma.
AB  - Tumors originating from ectopic adrenal tissue are relatively rare. In this
      article, we describe a case with Cushing's syndrome caused by an ectopic adrenal
      adenoma. A 38 year-old male patient presenting with cushingoid appearance for 2
      years was diagnosed to have ACTH-independent Cushing's syndrome based on
      endocrinological evaluation. Mutiple radiological examinations detected bilateral
      adrenal atrophy. When the images were investigated in a more expanded scope, a
      3.0*3.5*5.3 cm mass was detected in the anterior of left renal hilum and left
      renal vein. The mass was successfully resected with intraoperative endoscopy and
      pathological evaluation revealed an ectopic adrenal tumor. It is suggested that
      when the endocrinlogically confirmed adrenal neoplasm could not be well and
      definitely localized, the possibility of ectopic adrenal should be presumed and
      further radiography examinations should extend to the field where ectopic adrenal
      usually presents.

PMID- 22635082
TI  - A rare case of Interferon-alpha-Induced Hyperthyroidism in patients with  a
      chronic hepatitis C with granulocytopenia and transaminasemia treated
      successfully with radioiodine.
AB  - BACKGROUND: Conventional management of Interferon-alpha-Induced Hyperthyroidism
      (IIH) with radioactive iodine (RAI) may be used when treatment with beta blockers
      or antithyroid drugs (ATD), proves ineffective or is contraindicated. CASE
      PRESENTATION: We present a 38-year-old woman who has been treated with combined
      pegylated interferon alpha (INF-alpha) and Ribavirin for chronic hepatitis C.
      Destructive thyrotoxicosis appeared after four months of continuous IFN-alpha
      therapy and a beta blocker was prescribed. Initially, the patient presented
      normal TSH 2.4 uIU/mL, however during therapy with INF-alpha, TSH diminished to
      0.05 and thyroid hormones were elevated: fT4 23.1 pmol/L, fT3 7.2 pmol/L.
      Ultrasound examination showed completely irregular and greatly decreased
      echogenicity of the thyroid gland. The radioiodine uptake (RAIU) was deeply
      decreased to 2 and 3% at 5 h and 24 h, respectively. The thyroid scintiscan
      showed lack of isotope accumulation. Hypothyroidism developed and L-thyroxine was
      prescribed. The following year, hyperthyroidism reoccurred with TSH 0.08 uIU/mL,
      fT4 26.4 pmol/L, fT3 8.2 pmol/L, positive TSHR-Abs 6.2 (normal <2 IU/L) and mild
      Graves' Ophthalmopathy (GO). RAIU values were 23% at 5 h and 46% at 24 h. Thyroid
      scintiscan showed diffuse goiter. At this point beta blocker was introduced and
      ATD was started. After three months of therapy an increased level of
      aminotransferases and granulocytopaenia were observed. Hence, the patient
      received RAI and glucocorticosteroid, while INF-alpha therapy was continued.
      After approximately 4 months, hypothyroidism reappeared with insignificantly
      raised TSH level. One year later the patient was euthyroid and required no
      further treatment. CONCLUSIONS: Our report suggests that: 1. Radioiodine therapy
      might be an effective and safe method of treatment in cases of IIH with mild GO.
      2. IFN-alpha therapy need not be discontinued in patients with IIH.

PMID- 22635083
TI  - Combined octreotide and peptide receptor radionuclide therapy ((90)Y-DOTA-TATE)
      in case of malignant insulinoma.
AB  - BACKGROUND: Insulinomas are the most common functioning neuroendocrine tumours of
      the pancreas. Hypoglycemia due to excessive production of insulin is a main
      feature of this disease. Usually these neoplasms are benign and single with
      surgical excision as a treatment of choice. About 10% are malignant with tendency
      to form metastases especially to the liver then therapy requires various medical
      technics. CASE REPORT: 43 years old female with reccurent syncopies in course of
      hypoglycemia was admitted to the hospital to be diagnosed. Having suspected
      pathology within the pancreas the abdominal MRI was performed. It showed presence
      of numerous metastatic changes in the liver with no any other deviations in the
      abdomen including pancreas. Subsequent 18FDG PET-CT revealed metastases to the
      regional lymph nodes and the liver and suggested the presence of a primary lesion
      in the tail of the pancreas which was confirmed in EUS. Surgical excision of the
      tail of the pancreas was done. Pathological result: pancreatic neuroendocrine
      well differetiated cancer. Due to the recurrence of hypoglycemia patient was
      admitted to Department of Endocrinology where somatostatin analogue scintigraphy
      showed the presence of tracer accumulation foci in the liver. Combined long
      acting somatostatin analogue (octreotide) and peptide radionuclide receptor
      ((90)Y-DOTA-TATE) therapy were introduced. Stable blood glucose levels with no
      tendency to hypoglycemia and partial regression (PR) of liver lesions according
      to RECIST citeria were observed in course of the treatment.

PMID- 22635084
TI  - Nitrosative stress induces proliferation and viability changes in high glucose
      exposed rat Schwannoma cells.
AB  - OBJECTIVES: Schwann cells may be involved in the pathogenesis of several
      neuropathies, such as those linked to an excess of d-glucose. Indeed,
      hyperglicemic condition can often result in the production of high
      reactive/nitrosative oxygen species concentration and possible damage of several
      cell structures. In the present work attention has been focused on the possible
      nitrosative effect of hyperglycemia on RT4 Schwannoma cell lines. METHODS: Cells
      were cultured for 72hrs in the presence of 180 mM D-glucose. Morphology, growth
      rate, cell viability, catalase evaluation and Western blot were performed.
      RESULTS: In D-glucose-exposed cells, 3-Nitrotyrosine increase and subsequent
      modifications in cell morphology, growth rate, viability and catalase activity
      were found. CONCLUSION: Our findings suggested a possible primary role played by
      Schwann cells in the hyperglicemic neuropathy pathogenesis, through the excessive
      production of RNS and a decrease in antioxidant defense systems, bearing out the
      importance of the "nitrosative hypothesis" in the hyperglicemic-induced nervous
      system complications.

PMID- 22635085
TI  - A woman with thyrotoxicosis- and hyperemesis gravidarum-associated Wernicke's
      encephalopathy.
AB  - Although hyperthyroidism arising from primary thyroid disease is rare in
      pregnancy, transient gestational hyperthyroidism is not uncommon. This condition
      can be associated with hyperemesis gravidarum (HG), and Wernicke's
      encephalopathy. We present the case of a woman with toxic nodular goiter
      complicating HG-associated Wernicke's encephalopathy.  A 38-year-old Caucasian
      woman, who had received a diagnosis of hyperthyroidism and HG early in her
      pregnancy, had intrauterine fetal death at Week 16 of gestation. One day after
      undergoing therapeutic abortion, she was admitted to our clinic with persistent
      thyrotoxicosis, nausea, and vomiting. A toxic thyroid nodule was detected. She
      was given antithyroid medication, total parenteral nutrition. On Day 10 of
      hospitalization, she developed ataxia, aphasia, and somnolence. Cranial magnetic
      resonance imaging showed increased bilateral thalamic signalization. She was
      given a diagnosis of Wernicke's metabolic encephalopathy, for which she received
      thiamine and multivitamin preparations. She responded dramatically on the second
      day of thiamine therapy. Her consciousness improved rapidly and she began to
      speak. Her muscle tone was slightly weak and she had paresthesias in both legs. 
      Absorption of thiamine may be particularly impaired in pregnant women with
      hyperemesis and hyperthyroid disease. Wernicke's encephalopathy should be
      considered in hyperthyroid women with HG who develop neurological abnormalities.

PMID- 22635086
TI  - Biochemical behaviour of an incidentally diagnosed silent corticotroph adenoma.
AB  - Silent corticotroph adenoma (SCA) is a non-functioning macroadenoma that has
      positive immunoreactivity for ACTH. Few studies have evaluated the biochemical
      behaviour of these tumours. We present the case of a 65-year-old male
      incidentally diagnosed with SCA, in which an exhaustive study of the corticotroph
      axis was conducted.

PMID- 22635087
TI  - Coronary artery disease is not associated with stroke recurrence.
AB  - BACKGROUND: Coronary artery disease (CAD) is a leading cause of long-term
      mortality in Europe and it negatively influences the outcome after stroke.
      However, its influence on stroke recurrence which endangers stroke patients
      mostly in the first months following stroke, is unclear. Previous studies have
      found no association between CAD and ischemic stroke recurrence. However,
      assessment of the relationship was not the primary endpoint of these
      investigations. The aim of this study was to assess the possible association
      between CAD and stroke recurrence. PATIENTS AND METHODS: In a hospital-based,
      retrospective study, the set consisted of 190 patients - 105 patients with a
      first ever stroke (48 males; age 37-88, mean 70.7+/-12.5 years) and 85 patients
      with stroke recurrence (36 males; age 46-94, mean 88.0+/-9.6 years). CAD was
      correlated with the following other risk factors (age, sex, occurrence of
      arterial hypertension, atrial fibrillation, diabetes mellitus, plasma levels of
      total cholesterol, triglycerides, low-density cholesterol, high-density
      cholesterol, body mass index, presence of carotid plaques). Logistic regression
      analysis was used for the statistical evaluation. RESULTS: No significant
      association was found between CAD and stroke recurrence. Of all of the other
      observed risk factors, only age showed a significant association with stroke
      recurrence (OR 1.04, 95% CI: 1.02-1.07). CONCLUSION: The results of the presented
      study indicate that CAD does not influence stroke recurrence.

PMID- 22635088
TI  - Unfavorable effects of hyperprolactinemia in autoimmune endocrine disorders.
AB  - Prolactin is a hormone with a multidirectional proinflammatory action. It has an
      anti-apoptotic effect, enhances proliferative response to antigens and mitogens,
      as well as enhances the production of immunoglobulins and autoantibodies.
      Increased prolactin levels are commonly observed in various organ and multi-organ
      specific autoimmune diseases. In our article, we report a case of a woman who
      developed progression of autoimmune thyroid disorder and developed insufficiency
      of the zona glomerulosa when her prolactin levels were increased. A normalization
      of plasma prolactin levels by quinagolide and replacement of risperidone with
      aripiprazole improved her clinical condition. Our study suggests that, in some
      patients, hyperprolactinemia may predispose to the development and progression of
      autoimmune disorders of endocrine glands.

PMID- 22635089
TI  - Coexistence of growth hormone deficiency and autoimmune polyglandular syndrome
      type 3.
AB  - Both adult-onset growth hormone deficiency and autoimmune polyglandular syndrome
      are more frequent clinical entities than previously thought. In light of research
      carried out in recent years, it seems that growth hormone deficiency may be
      associated with proinflammatory state. This study describes a unique case of
      adult-onset growth hormone deficiency secondary to a traumatic brain injury in a
      young man, which was followed by the development of autoimmune polyglandular
      syndrome type 3. We discuss diagnostic and treatment dilemmas associated with
      discovering and management of both disorders in this patient. We conclude that in
      predisposed individuals growth hormone deficiency may lead to the development of
      autoimmune disorders of endocrine glands and/or exacerbate their clinical course.

PMID- 22635090
TI  - Teratology on the crossroads: historical aspects and modern approaches.
AB  - Teratology is the science of congenital developmental disorders (CDDs), overt or
      latent defects of the organism resulting from the effect of internal and external
      factors on developmental processes. In this article the significance and position
      of present-day teratology is discussed in the context of development of this
      branch of science and related disciplines. The authors present an updated
      overview of the most important milestones and stages of the development of
      teratology. Based on the analysis of the historical development of theses and
      theories that represent a decisive contribution to this field, we present a
      survey of the fundamental principles of experimental and clinical teratology. The
      aim of observing these principles is to get insight into developmental relations
      and to understand mechanisms of action on the level of cell populations
      (elementary morphogenetic processes), tissues and organs. It is important to
      realize that any negative intervention into the normal course of these processes,
      either on genetic or non-genetic basis, inevitably leads to a sequence of
      subsequent changes resulting in the development of congenital developmental
      disorders.  Despite modern approaches of molecular biology and genetics, along
      with top diagnostic techniques, we are still not able to identify the actual
      cause in more than 50% of all congenital defects. One-half of the unidentified
      cases are referred to as "multifactorial", a term that is rather ambiguous. It
      either means that some of the basic principles of teratogenesis still escape our
      attention, or the interpretation of some of the well known principles might be
      misleading. A third possibility is rather pessimistic. The development of the
      individual is so sophisticated and dependent on a delicate network of a multitude
      of factors mutually affecting each other that it is extremely prone to give rise
      to a plethora of spontaneous errors which are unpredictable and impossible to
      prevent. Nevertheless, the long and complicated history of scientific endeavour
      has yielded considerable present-day knowledge on causes and mechanisms of CDDs,
      a history whose beginnings date back to antiquity.

PMID- 22635091
TI  - A possible role of perinatal light in mood disorders and internal cancers:
      reconciliation of instability and latitude concepts.
AB  - Thought-provoking experimental evidence suggests that perinatal light exposure
      may imprint circadian clocks with lasting effects on the alignment and the
      stability of circadian rhythms later in life. Assuming that exposure to light
      early in life could determine the stability of an individual's circadian system
      later in life, the present hypothesis proposes that time of year and location of
      birth (i.e., season and latitude) and thus differential Zeitgeber strengths may
      be key contributors to a person's susceptibility of developing mood disorders
      like seasonal affective disorder (SAD) and common internal cancers such as those
      of breast and prostate. Consequently, when and where people are born might
      critically predispose them to both mood disorders and internal cancers, and may
      affect the onset and course of such illnesses. This paper develops a causal
      framework and presents suggestions for rigorous tests of the associated corollary
      and predictions.  It does not escape our attention that links between the
      perinatal Zeitgeber strength of light and its effects on the stability of
      circadian systems later in life could have a role to play in affecting long-term
      health beyond cancer and mood disorders - mostly in adults but also in children.

PMID- 22635092
TI  - A perinatal signature of light on chronobiology? If so, numerous questions arise
      and experimental animal research must provide more information.
AB  - That light and melatonin rhythms provide both clock and calendar information in
      humans and numerous other species is beyond dispute; this holds true for all
      stages of life, including the very early ones. Experimental evidence elucidates
      that exposure to light and melatonin titres are keys for the very development of
      circadian and seasonal rhythms. As evinced by a 2011 publication in Nature
      Neuroscience such awareness could impact considerably on the design and conduct
      of experimental studies as well as their subsequent analyses, interpretations and
      comparisons. Therefore "when and how experimental animals were bred, developed
      and raised" may be critical when experimenting with animals generally, and not
      just rodents. As long as the suggested imprinting of circadian system stability
      via light cues is not falsified, the perinatal season or perinatal experimental
      light:dark [L:D] conditions that an animal was kept under should be routinely
      recorded, published and considered in analysing and interpreting study data.

PMID- 22635093
TI  - Evidence for a negative association between schizophrenia and a polymorphism in
      the insulin receptor substrate-3 (IRS-3) gene.
AB  - OBJECTIVES: Since there are clear indications that schizophrenia is a systemic
      disorder, we sought for a common molecular basis for schizophrenia abnormalities
      in brain and body. Our hypothesis was that an impaired insulin and insulin-like
      growth factor signalling in cells might underlie changes in both brain and body
      in schizophrenia. In this regard, the insulin receptor substrates 1-4, linking
      both the insulin and insulin-like growth factor-1 receptors with intracellular
      pathways, might be of interest to study genetically. In the present study, we
      chose to study the insulin receptor substrate-3 (IRS-3) gene as a candidate gene
      in schizophrenia. METHODS: The IRS-3 gene of 93 patients with the diagnosis of
      schizophrenia according to DSM-IV criteria and 57 healthy control subjects was
      screened for DNA sequence variations, followed by case-control analyses of total
      10 detected polymorphisms. RESULTS: The A/G genotype of the single nucleotide
      polymorphism (SNP) rs117078492 in the IRS-3 gene occurred in 5.3% of the control
      subjects compared with in 0% of the patients (p=0.05). Similarly, the haplotypes
      5 and 3X, constructed from polymorphisms in the IRS-3 gene and including the A
      allele of this A/G SNP, occurred only in the control subjects and not in the
      patients (5.3% vs 0%, p=0.05). CONCLUSION: Our findings suggest that individuals
      carrying the A allele of this A/G SNP in the IRS-3 gene as well as the estimated
      haplotypes 5 or 3X including this A allele, have a protection against
      schizophrenia development.

PMID- 22635094
TI  - High concentration of ghrelin in children with growth hormone deficiency and
      neurosecretory dysfunction.
AB  - BACKGROUND: The role of endogenous ghrelin in the growth process of children is
      unclear. The aim of the present study was to assess ghrelin concentrations in
      children with growth hormone deficiency (GHD), neurosecretory dysfunction (NSD)
      and idiopathic short stature (ISS) in comparison to healthy controls. MATERIAL:
      One hundred and forty seven children (61 girls and 86 boys), aged 3.7-16.8 years
      (mean+/-SD: 10.7+/-3.44 years) with short stature (below -2.0 SD) were qualified
      into the study. In each child, fasting ghrelin and insulin-like growth factor
      type I (IGF-I) concentrations were measured and growth hormone (GH) secretion was
      assessed after falling asleep and during two GH-stimulating tests. According to
      maximal GH concentrations, children were qualified into GHD, NSD and ISS group.
      Additionally, depending on biological development, the children were divided on
      younger and older subgroups. The control group consisted of 19 healthy children
      with normal height and body mass. RESULTS: Ghrelin concentrations in GHD
      (1847.5+/-1444.3 pg/mL) and NSD (1809.3+/-983.5 pg/mL) were significantly higher
      than in ISS (1218.1+/-646.8 pg/mL) and in Controls (924.9+/-318.4 pg/mL). A
      comparison of ghrelin concentrations in older and younger children within the
      same diagnostic group, showed statistically higher ghrelin levels in younger than
      in older children (except of NSD group, in which the difference reached the
      border of statistical significance). CONCLUSIONS: Ghrelin concentration is
      elevated in GHD and NSD children. Independently of GH and IGF-I secretion
      disorders type, ghrelin concentrations decrease with the children' age. The
      higher concentration of ghrelin in ISS than in Controls suggests the presence of
      GH-independent factors increasing ghrelin secretion by X/A cells in the gastric
      oxyntic mucosa.

PMID- 22635095
TI  - Optimal effective doses of cabergoline and bromocriptine and valvular leasions in
      men with prolactinomas.
AB  - OBJECTIVES: Prolactinoma is the most common pituitary adenoma, and dopamine
      agonists( BRC, and CAB) is the primary therapy. Recently, the increased
      prevalance of cardiac valvular disease in patients treated with DAs for
      Parkinson's disease has raised concerns about the safety of this drug in patients
      with prolactinoma. CAB and pergolide are frequently reported to cause
      valvulopathy, there are very few studies showing this side effect in BRC
      administiration which has less potent agonism of 5-HT2B receptors. Male patients
      who are known to have higher prevalance of macroadenomas compared to women. The
      dosage of DAs administered were rarely evaluated. METHODS: We performed a
      retrospective chart to evaluate the medical management and treatment outcomes of
      male patients with macro/giant prolactinomas. We evaluated 22 patients with
      prolactinoma managed with DAs therapy alone for at least 1 year. All patients
      were followed for a mean of 61 months. Pretreatment echocardiographic examination
      were not available at that time. RESULTS: None of them had any resistance or
      intolerance to DAs. The mean tumor shrinkage was 62%. In three patients the
      macroprolactinoma disappeared, in two patients the tumor shrinkage was 93% and
      70%. The DAs therapy was discontinued in these patient. After a follow up neither
      MRI showed a recurrence or enlargement of the adenoma, nor prolactin levels
      showed any elevation. The echocardiography were performed at the last visit of
      each patient and no valvulopathy in any of the patients on DAs therapy were
      detected. CONCLUSIONS: DAs are effective, and safe for valve morphology with mean
      cumulative doses of 155 mg CAB, and 7 301 mg BRC in patients with
      macroprolactinoma.

PMID- 22635096
TI  - Clinical and cognitive correlates of formal thought disorder in early onset
      schizophrenia.
AB  - OBJECTIVE: Although formal thought disorder and cognitive impairment are key
      features of schizophrenia, only a few studies evaluated both in adolescent
      population. METHOD: 32 inpatients with early-onset schizophrenia spectrum
      disorders (SSD) and 32 matched healthy controls were studied with Thought,
      Language and Communication Scale and battery of neurocognitive tests and SSD
      subjects were also assessed with Positive and Negative Syndrome Scale and
      Clinical Global Impression Scale. RESULTS: Patients presented impairment in both
      cognitive functioning and formal thought processes. Communication disturbances
      correlated with executive and verbal fluency dysfunction. CONCLUSION:
      Communication disturbances in adolescent SSD patients may have both dysexecutive
      and dyssemantic origin.

PMID- 22635097
TI  - Quantification of the affinities and kinetics of protein interactions using
      silicon nanowire biosensors.
AB  - Monitoring the binding affinities and kinetics of protein interactions is
      important in clinical diagnostics and drug development because such information
      is used to identify new therapeutic candidates. Surface plasmon resonance is at
      present the standard method used for such analysis, but this is limited by low
      sensitivity and low-throughput analysis. Here, we show that silicon nanowire
      field-effect transistors can be used as biosensors to measure protein-ligand
      binding affinities and kinetics with sensitivities down to femtomolar
      concentrations. Based on this sensing mechanism, we develop an analytical model
      to calibrate the sensor response and quantify the molecular binding affinities of
      two representative protein-ligand binding pairs. The rate constant of the
      association and dissociation of the protein-ligand pair is determined by
      monitoring the reaction kinetics, demonstrating that silicon nanowire field
      effect transistors can be readily used as high-throughput biosensors to quantify
      protein interactions.

PMID- 22635098
TI  - Emissive ZnO-graphene quantum dots for white-light-emitting diodes.
AB  - Hybrid nanostructures combining inorganic materials and graphene are being
      developed for applications such as fuel cells, batteries, photovoltaics and
      sensors. However, the absence of a bandgap in graphene has restricted the
      electrical and optical characteristics of these hybrids, particularly their
      emissive properties. Here, we use a simple solution method to prepare emissive
      hybrid quantum dots consisting of a ZnO core wrapped in a shell of single-layer
      graphene. We then use these quantum dots to make a white-light-emitting diode
      with a brightness of 798 cd m(-2). The strain introduced by curvature opens an
      electronic bandgap of 250 meV in the graphene, and two additional blue emission
      peaks are observed in the luminescent spectrum of the quantum dot. Density
      functional theory calculations reveal that these additional peaks result from a
      splitting of the lowest unoccupied orbitals of the graphene into three orbitals
      with distinct energy levels. White emission is achieved by combining the quantum
      dots with other emissive materials in a multilayer light-emitting diode.

PMID- 22635099
TI  - An oxygen reduction electrocatalyst based on carbon nanotube-graphene complexes.
AB  - Oxygen reduction reaction catalysts based on precious metals such as platinum or
      its alloys are routinely used in fuel cells because of their high activity.
      Carbon-supported materials containing metals such as iron or cobalt as well as
      nitrogen impurities have been proposed to increase scalability and reduce costs,
      but these alternatives usually suffer from low activity and/or gradual
      deactivation during use. Here, we show that few-walled carbon nanotubes,
      following outer wall exfoliation via oxidation and high-temperature reaction with
      ammonia, can act as an oxygen reduction reaction electrocatalyst in both acidic
      and alkaline solutions. Under a unique oxidation condition, the outer walls of
      the few-walled carbon nanotubes are partially unzipped, creating nanoscale sheets
      of graphene attached to the inner tubes. The graphene sheets contain extremely
      small amounts of irons originated from nanotube growth seeds, and nitrogen
      impurities, which facilitate the formation of catalytic sites and boost the
      activity of the catalyst, as revealed by atomic-scale microscopy and electron
      energy loss spectroscopy. Whereas the graphene sheets formed from the unzipped
      part of the outer wall of the nanotubes are responsible for the catalytic
      activity, the inner walls remain intact and retain their electrical conductivity,
      which facilitates charge transport during electrocatalysis.

PMID- 22635101
TI  - Tin(IV) and lead(IV) complexes with a tetradentate redox-active ligand.
AB  - The coordination chemistry of a tetradentate redox-active ligand, glyoxal-bis(2
      hydroxy-3,5-di-tert-butylanil) (H(2)L), was investigated with the diorganotin(IV)
      and diphenyllead(IV) moieties. Complexes R(2)SnL (R = Me (1), Et (2), (t)Bu (3),
      Ph (4)) and Ph(2)PbL (5) have been prepared and characterized. The molecular
      structures of compounds 1, 3, and 5 have been determined by single crystal X-ray
      diffraction. The diamagnetic octahedral complexes bear a tetradentate O,N,N,O
      redox-active ligand with a nearly planar core. Complexes 1-5 demonstrate
      solvatochromism in solution. The CV of complexes 1-5 reveals four one-electron
      redox processes. The spin density distribution in the chemically generated
      cations and anions of 1-5 was studied by X-band EPR spectroscopy. The
      experimental data agree well with the results of DFT calculations of electronic
      structures for 1, its pyridine adduct 1.Py, cation 1(+) and anion 1(-).

PMID- 22635100
TI  - Cell-free protein synthesis and assembly on a biochip.
AB  - Biologically active complexes such as ribosomes and bacteriophages are formed
      through the self-assembly of proteins and nucleic acids. Recapitulating these
      biological self-assembly processes in a cell-free environment offers a way to
      develop synthetic biodevices. To visualize and understand the assembly process, a
      platform is required that enables simultaneous synthesis, assembly and imaging at
      the nanoscale. Here, we show that a silicon dioxide grid, used to support samples
      in transmission electron microscopy, can be modified into a biochip to combine in
      situ protein synthesis, assembly and imaging. Light is used to pattern the
      biochip surface with genes that encode specific proteins, and antibody traps that
      bind and assemble the nascent proteins. Using transmission electron microscopy
      imaging we show that protein nanotubes synthesized on the biochip surface in the
      presence of antibody traps efficiently assembled on these traps, but pre
      assembled nanotubes were not effectively captured. Moreover, synthesis of green
      fluorescent protein from its immobilized gene generated a gradient of captured
      proteins decreasing in concentration away from the gene source. This biochip
      could be used to create spatial patterns of proteins assembled on surfaces.

PMID- 22635102
TI  - The metal theory of Alzheimer's disease.
AB  - Brain homeostasis of transition metals is severely perturbed in Alzheimer's
      disease (AD), with extracellular pooling of zinc and copper in amyloid, and
      intraneuronal accumulation of iron. Rapidly accumulating evidence indicates that
      these perturbances themselves may contribute significantly to the cognitive loss
      and neurodegeneration, even in the absence of AD proteopathy. There is now strong
      evidence that each of the major protein participants in AD pathology has
      physiologically important interactions with transition metals: AbetaPP is the
      neuronal iron export ferroxidase with a major interaction with ferroportin,
      presenilins are needed for the import of ~ 50% of cellular copper and zinc, and
      tau promotes the export of neuronal iron by facilitating the trafficking of
      AbetaPP to the surface. Therefore, amyloid and tau pathology arise in a milieu of
      constitutively high metal flux, and the major components of AD pathology may
      contribute to the disease by failing in their metal transport roles.

PMID- 22635103
TI  - Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss
      in vasculotropic mutant amyloid-beta protein Tg-SwDI mice.
AB  - Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's
      disease and cerebral amyloid angiopathy (CAA), where the epsilon4 allele
      increases and the epsilon2 allele decreases the risk for developing disease.
      Specific mutations within the amyloid-beta (Abeta) peptide have been identified
      that cause familial forms of CAA. However, the influence of APOE genotype on
      accumulation of CAA mutant Abeta in brain is not well understood. Earlier, we
      showed that human ApoE4 redistributes fibrillar amyloid deposition from the
      cerebral microvasculature to parenchymal plaques in Tg-SwDI mice, a model that
      accumulates human Dutch/Iowa (E22Q/D23N) CAA mutant Abeta in brain (Xu et al., J
      Neurosci 28, 5312-5320, 2008). Human ApoE2 can reduce Abeta pathology in
      transgenic models of parenchymal plaques. Here we determined if human ApoE2 can
      influence the location and severity of amyloid pathology in Tg-SwDI mice.
      Comparing Tg-SwDI mice bred onto a human APOE2/2 or human APOE4/4 background, we
      found there was no change in the brain levels of total Abeta(40) and Abeta(42)
      compared to mice on the endogenous mouse APOE background. In Tg-SwDI mice on
      either human APOE background, there was a similarly strong reduction in the
      levels of microvascular CAA and emergence of extensive parenchymal plaque
      amyloid. In both Tg-SwDI-hAPOE2/2 and Tg-SwDI-hAPOE4/4 mice, the distribution of
      ApoE proteins and neuronal loss were associated with parenchymal amyloid plaques.
      These findings suggest that compared with human ApoE4, human ApoE2 does not
      beneficially influence the quantitative or spatial accumulation of human
      Dutch/Iowa CAA mutant amyloid or associated pathology in transgenic mice.

PMID- 22635104
TI  - Involvement of insulin-like growth factor 1 receptor signaling in the amyloid
      beta peptide oligomers-induced p75 neurotrophin receptor protein expression in
      mouse hippocampus.
AB  - The p75 neurotrophin receptor (p75NTR) has been thought to play a critical role
      in amyloid-beta peptide (Abeta)-mediated neurodegeneration and Abeta metabolism
      in Alzheimer's disease (AD) brains. Our previous report showed that membrane
      associated p75NTR protein expression was significantly increased in the
      hippocampi of two different strains of transgenic AD mice and was associated with
      the age-dependent elevation of Abeta1-42 levels. Here, we provide evidence that
      the Abeta1-42 oligomers known as ADDLs (Abeta-derived diffusible ligands) induce
      p75NTR protein expression through insulin-like growth factor 1 receptor (IGF-1R)
      phosphorylation in SH-SY5Y human neuroblastoma cells. An in vivo microinjection
      study demonstrated that microinjected ADDLs increased the p75NTR protein
      expression by 1.4-fold in the ipsilateral hippocampus compared to the
      contralateral hippocampus. In addition, ADDLs microinjected into mouse hippocampi
      facilitated IGF-1R phosphorylation within 30 min and the co-administration of
      picropodophyllin, an IGF-1R kinase inhibitor, blocked ADDLs-induced p75NTR
      expression. We examined the possible involvement of IGF-1R in the increased
      p75NTR protein expression in the hippocampi of 6-month-old AbetaPPswe/PS1dE9 AD
      model mice that had accumulated significant amounts of Abeta1-42 and showed
      significantly higher p75NTR expression than age-matched wild-type mice. We found
      that IGF-1R phosphorylation in these transgenic mice was higher than that in the
      wild-type mice. These findings indicate that Abeta1-42 oligomers stimulate the
      p75NTR protein expression in the hippocampus through IGF-1R signaling. Thus,
      Abeta1-42 oligomers-mediated IGF-1R activation may trigger an increase in p75NTR
      protein expression in the hippocampus of AD brain during the early stages of
      disease development.

PMID- 22635105
TI  - Elucidating the triggers, progression, and effects of Alzheimer's disease.
AB  - As the number of patients with Alzheimer's disease (AD) continues to rise, the
      need for efficacious therapeutics is becoming more and more urgent. Understanding
      the molecular relationship and interactions between Abeta and tau and their
      contribution to cognitive decline remain one of the most fundamental and
      unresolved questions in the AD field. Likewise, elucidating the initial triggers
      of disease pathology, as well as the impact of various factors such as stress and
      inflammation on disease progression, are equally important to fully understand
      this devastating disorder. Here we discuss recent studies that have illuminated
      the importance of key facilitators of disease progression using the 3xTg-AD and
      CaM/Tet-DTA mouse models, and suggest viable targets for ameliorating both
      molecular pathology and cognitive decline.

PMID- 22635106
TI  - Synergistic antitumor effect of TRAIL and IL-24 with complete eradication of
      hepatoma in the CTGVT-DG strategy.
AB  - The ZD55-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and ZD55
      interleukin (IL)-24 were constructed by inserting TRAIL or IL-24 gene separately
      into the oncolytic adenovirus named ZD55 (with adenovirus E1B-55kD deletion). The
      resulting ZD55-TRAIL and ZD55-IL-24 were used in combination to treat xenograft
      tumors in nude mice model. The results showed that it can not only completely
      eliminate BEL7404 hepatoma xenograft but also have excellent antitumor effect
      against gaster, lung, prostate, and breast carcinomas. It was also found that
      ZD55-TRAIL could not only suppress the tumor growth promoting effect by ZD55-IL
      24 at lower dosage, but also substantially reduce the cancer cell viability in
      their combined use. This is because ZD55-IL-24 and ZD55-TRAIL could mutually
      enhance each other's antitumor effect greatly. All these findings conspicuously
      showed the synergistic antitumor effect of TRAIL and IL-24, which is also the
      reason for the antitumor effect by the combined use of TRAIL and IL-24 in vitro
      and also in vivo.

PMID- 22635107
TI  - Solid phase synthesis of a functionalized bis-peptide using "safety catch"
      methodology.
AB  - In 1962, R.B. Merrifield published the first procedure using solid-phase peptide
      synthesis as a novel route to efficiently synthesize peptides. This technique
      quickly proved advantageous over its solution-phase predecessor in both time and
      labor. Improvements concerning the nature of solid support, the protecting groups
      employed and the coupling methods employed over the last five decades have only
      increased the usefulness of Merrifield's original system. Today, use of a Boc
      based protection and base/nucleophile cleavable resin strategy or Fmoc-based
      protection and acidic cleavable resin strategy, pioneered by R.C. Sheppard, are
      most commonly used for the synthesis of peptides(1).    Inspired by Merrifield's
      solid supported strategy, we have developed a Boc/tert-butyl solid-phase
      synthesis strategy for the assembly of functionalized bis-peptides(2), which is
      described herein. The use of solid-phase synthesis compared to solution-phase
      methodology is not only advantageous in both time and labor as described by
      Merrifield(1), but also allows greater ease in the synthesis of bis-peptide
      libraries. The synthesis that we demonstrate here incorporates a final cleavage
      stage that uses a two-step "safety catch" mechanism to release the functionalized
      bis-peptide from the resin by diketopiperazine formation.    Bis-peptides are
      rigid, spiro-ladder oligomers of bis-amino acids that are able to position
      functionality in a predictable and designable way, controlled by the type and
      stereochemistry of the monomeric units and the connectivity between each monomer.
      Each bis-amino acid is a stereochemically pure, cyclic scaffold that contains two
      amino acids (a carboxylic acid with an alpha-amine)(3,4). Our laboratory is
      currently investigating the potential of functional bis-peptides across a wide
      variety of fields including catalysis, protein-protein interactions and
      nanomaterials.

PMID- 22635108
TI  - Copper(I)/TEMPO-catalyzed aerobic oxidation of primary alcohols to aldehydes with
      ambient air.
AB  - This protocol describes a practical laboratory-scale method for aerobic oxidation
      of primary alcohols to aldehydes, using a chemoselective Cu(I)/TEMPO (TEMPO =
      2,2,6,6-tetramethyl-1-piperidinyloxyl) catalyst system. The catalyst is prepared
      in situ from commercially available reagents, and the reactions are performed in
      a common organic solvent (acetonitrile) with ambient air as the oxidant. Three
      different reaction conditions and three procedures for the isolation and
      purification of the aldehyde product are presented. The oxidations of eight
      different alcohols, described here, include representative examples of each
      reaction condition and purification method. Reaction times vary from 20 min to 24
      h, depending on the alcohol, whereas the purification methods each take about 2
      h. The total time necessary for the complete protocol ranges from 3 to 26 h.

PMID- 22635109
TI  - Production of avian retroviruses and tissue-specific somatic retroviral gene
      transfer in vivo using the RCAS/TVA system.
AB  - Spatiotemporal retroviral gene transfer into specific somatic mammalian cells
      using the avian RCAS (replication-competent avian sarcoma-leukosis virus long
      terminal repeat with splice acceptor)/tumor virus A (TVA) system is a versatile
      tool for performing lineage tracing and gene function analysis in vivo. RCAS
      retroviruses carrying the subgroup A envelope transduce only genetically
      engineered mammalian cells that express the cognate avian retroviral receptor
      TVA. The RCAS/TVA gene delivery system has been successfully used in various
      different mouse TVA-expression models. This protocol contains a detailed
      description of the production of high-titer RCAS retroviruses in chicken
      fibroblasts and the transduction of proliferating TVA-positive somatic mammalian
      cells in vivo. By taking advantage of the combination of the RCAS/TVA with the
      'universal' Cre/loxP system, the protocol can be used in nearly every
      proliferating cell type in vivo. The protocol takes 4 weeks from transfection of
      chicken fibroblasts, which act as the host cells for viral production, to the
      transduction of TVA-transgenic mice.

PMID- 22635110
TI  - Microwave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy
      4(1H)-quinolone and structurally related analogs.
AB  - An optimized procedure for the efficient preparation of 2-heptyl-3-hydroxy-4(1H)
      quinolone (Pseudomonas quinolone signal or PQS) and a diverse range of
      structurally related 2-alkyl-4-quinolones with biological activity is presented.
      The two-step synthesis begins with the formation of alpha-chloro ketones by the
      coupling of a Weinreb amide (2-chloro-N-methoxy-N-methylacetamide) and an
      appropriate Grignard reagent. The resulting alpha-chloro ketones can be reacted
      with commercially available anthranilic acids under microwave irradiation
      conditions to furnish the desired 2-alkyl-4-quinolone products. As a typical
      example, the synthesis of PQS, a molecule involved in quorum sensing in the
      pathogenic bacterium Pseudomonas aeruginosa, is described in detail. The first
      step of this process (alpha-chloro ketone formation) takes ~10 h in total to
      complete from commercially available bromoheptane and 2-chloro-N-methoxy-N
      methylacetamide. The second step (microwave-assisted reaction with anthranilic
      acid) takes ~14 h in total to complete (the reaction typically proceeds in ~30
      min, with work-up and purification requiring ~13 h).

PMID- 22635111
TI  - Guide to video recording of structure dynamics and dynamic processes of proteins
      by high-speed atomic force microscopy.
AB  - High-speed atomic force microscopy (HS-AFM) allows direct visualization of
      dynamic structural changes and processes of functioning biological molecules in
      physiological solutions, at subsecond to sub-100-ms temporal and submolecular
      spatial resolution. Unlike fluorescence microscopy, wherein the subset of
      molecular events that you see is dependent on the site where the probe is placed,
      dynamic molecular events unselectively appear in detail in an AFM movie,
      facilitating our understanding of how biological molecules function. Here we
      present protocols for HS-AFM imaging of proteins in action, including preparation
      of cantilever tips, step-by-step procedures for HS-AFM imaging, and recycling of
      cantilevers and sample stages, together with precautions and troubleshooting
      advice for successful imaging. The protocols are adaptable in general for imaging
      many proteins and protein-nucleic acid complexes, and examples are described for
      looking at walking myosin, ATP-hydrolyzing rotorless F(1)-ATPase and cellulose
      hydrolyzing cellulase. The entire protocol takes 10-15 h, depending mainly on the
      substrate surface to be used.

PMID- 22635112
TI  - Systems dynamic modeling of the stomatal guard cell predicts emergent behaviors
      in transport, signaling, and volume control.
AB  - The dynamics of stomatal movements and their consequences for photosynthesis and
      transpirational water loss have long been incorporated into mathematical models,
      but none have been developed from the bottom up that are widely applicable in
      predicting stomatal behavior at a cellular level. We previously established a
      systems dynamic model incorporating explicitly the wealth of biophysical and
      kinetic knowledge available for guard cell transport, signaling, and homeostasis.
      Here we describe the behavior of the model in response to experimentally
      documented changes in primary pump activities and malate (Mal) synthesis imposed
      over a diurnal cycle. We show that the model successfully recapitulates the
      cyclic variations in H+, K+, Cl-, and Mal concentrations in the cytosol and
      vacuole known for guard cells. It also yields a number of unexpected and
      counterintuitive outputs. Among these, we report a diurnal elevation in cytosolic
      free Ca2+ concentration and an exchange of vacuolar Cl- with Mal, both of which
      find substantiation in the literature but had previously been suggested to
      require additional and complex levels of regulation. These findings highlight the
      true predictive power of the OnGuard model in providing a framework for systems
      analysis of stomatal guard cells, and they demonstrate the utility of the OnGuard
      software and HoTSig library in exploring fundamental problems in cellular
      physiology and homeostasis.

PMID- 22635113
TI  - Arabidopsis sphingolipid fatty acid 2-hydroxylases (AtFAH1 and AtFAH2) are
      functionally differentiated in fatty acid 2-hydroxylation and stress responses.
AB  - 2-Hydroxy fatty acids (2-HFAs) are predominantly present in sphingolipids and
      have important physicochemical and physiological functions in eukaryotic cells.
      Recent studies from our group demonstrated that sphingolipid fatty acid 2
      hydroxylase (FAH) is required for the function of Arabidopsis (Arabidopsis
      thaliana) Bax inhibitor-1 (AtBI-1), which is an endoplasmic reticulum membrane
      localized cell death suppressor. However, little is known about the function of
      two Arabidopsis FAH homologs (AtFAH1 and AtFAH2), and it remains unclear whether
      2-HFAs participate in cell death regulation. In this study, we found that both
      AtFAH1 and AtFAH2 had FAH activity, and the interaction with Arabidopsis
      cytochrome b5 was needed for the sufficient activity. 2-HFA analysis of AtFAH1
      knockdown lines and atfah2 mutant showed that AtFAH1 mainly 2-hydroxylated very
      long-chain fatty acid (VLCFA), whereas AtFAH2 selectively 2-hydroxylated palmitic
      acid in Arabidopsis. In addition, 2-HFAs were related to resistance to oxidative
      stress, and AtFAH1 or 2-hydroxy VLCFA showed particularly strong responses to
      oxidative stress. Furthermore, AtFAH1 interacted with AtBI-1 via cytochrome b5
      more preferentially than AtFAH2. Our results suggest that AtFAH1 and AtFAH2 are
      functionally different FAHs, and that AtFAH1 or 2-hydroxy VLCFA is a key factor
      in AtBI-1-mediated cell death suppression.

PMID- 22635114
TI  - The vascular pathogen Verticillium longisporum requires a jasmonic acid
      independent COI1 function in roots to elicit disease symptoms in Arabidopsis
      shoots.
AB  - Verticillium longisporum is a soil-borne vascular pathogen that causes reduced
      shoot growth and early senescence in Arabidopsis (Arabidopsis thaliana). Here, we
      report that these disease symptoms are less pronounced in plants that lack the
      receptor of the plant defense hormone jasmonic acid (JA), CORONATINE INSENSITIVE1
      (COI1). Initial colonization of the roots was comparable in wild-type and coi1
      plants, and fungal DNA accumulated to almost similar levels in petioles of wild
      type and coi1 plants at 10 d post infection. Completion of the fungal life cycle
      was impaired in coi1, as indicated by the reduced number of plants with
      microsclerotia, which are detected on dead plant material at late stages of the
      disease. Contrary to the expectation that the hormone receptor mutant coi1 should
      display the same phenotype as the corresponding hormone biosynthesis mutant
      delayed dehiscence2 (dde2), dde2 plants developed wild-type-like disease
      symptoms. Marker genes of the JA and the JA/ethylene defense pathway were induced
      in petioles of wild-type plants but not in petioles of dde2 plants, indicating
      that fungal compounds that would activate the known COI1-dependent signal
      transduction chain were absent. Grafting experiments revealed that the
      susceptibility-enhancing COI1 function acts in the roots. Moreover, we show that
      the coi1-mediated tolerance is not due to the hyperactivation of the salicylic
      acid pathway. Together, our results have unraveled a novel COI1 function in the
      roots that acts independently from JA-isoleucine or any JA-isoleucine mimic. This
      COI1 activity is required for a yet unknown root-to-shoot signaling process that
      enables V. longisporum to elicit disease symptoms in Arabidopsis.

PMID- 22635115
TI  - Arabidopsis ECERIFERUM9 involvement in cuticle formation and maintenance of plant
      water status.
AB  - Mutation of the ECERIFERUM9 (CER9) gene in Arabidopsis (Arabidopsis thaliana)
      causes elevated amounts of 18-carbon-length cutin monomers and a dramatic shift
      in the cuticular wax profile (especially on leaves) toward the very-long-chain
      free fatty acids tetracosanoic acid (C24) and hexacosanoic acid (C26). Relative
      to the wild type, cer9 mutants exhibit elevated cuticle membrane thickness over
      epidermal cells and cuticular ledges with increased occlusion of the stomatal
      pore. The cuticular phenotypes of cer9 are associated with delayed onset of
      wilting in plants experiencing water deficit, lower transpiration rates, and
      improved water use efficiency measured as carbon isotope discrimination. The CER9
      protein thus encodes a novel determinant of plant drought tolerance-associated
      traits, one whose deficiency elevates cutin synthesis, redistributes wax
      composition, and suppresses transpiration. Map-based cloning identified CER9, and
      sequence analysis predicted that it encodes an E3 ubiquitin ligase homologous to
      yeast Doa10 (previously shown to target endoplasmic reticulum proteins for
      proteasomal degradation). To further elucidate CER9 function, the impact of CER9
      deficiency on interactions with other genes was examined using double mutant and
      transcriptome analyses. For both wax and cutin, cer9 showed mostly additive
      effects with cer6, long-chain acyl-CoA synthetase1 (lacs1), and lacs2 and
      revealed its role in early steps of both wax and cutin synthetic pathways.
      Transcriptome analysis revealed that the cer9 mutation affected diverse cellular
      processes, with primary impact on genes associated with diverse stress responses.
      The discovery of CER9 lays new groundwork for developing novel cuticle-based
      strategies for improving the drought tolerance and water use efficiency of crop
      plants.

PMID- 22635116
TI  - OnGuard, a computational platform for quantitative kinetic modeling of guard cell
      physiology.
AB  - Stomatal guard cells play a key role in gas exchange for photosynthesis while
      minimizing transpirational water loss from plants by opening and closing the
      stomatal pore. Foliar gas exchange has long been incorporated into mathematical
      models, several of which are robust enough to recapitulate transpirational
      characteristics at the whole-plant and community levels. Few models of stomata
      have been developed from the bottom up, however, and none are sufficiently
      generalized to be widely applicable in predicting stomatal behavior at a cellular
      level. We describe here the construction of computational models for the guard
      cell, building on the wealth of biophysical and kinetic knowledge available for
      guard cell transport, signaling, and homeostasis. The OnGuard software was
      constructed with the HoTSig library to incorporate explicitly all of the
      fundamental properties for transporters at the plasma membrane and tonoplast, the
      salient features of osmolite metabolism, and the major controls of cytosolic-free
      Ca2+ concentration and pH. The library engenders a structured approach to tier
      and interrelate computational elements, and the OnGuard software allows ready
      access to parameters and equations 'on the fly' while enabling the network of
      components within each model to interact computationally. We show that an OnGuard
      model readily achieves stability in a set of physiologically sensible baseline or
      Reference States; we also show the robustness of these Reference States in
      adjusting to changes in environmental parameters and the activities of major
      groups of transporters both at the tonoplast and plasma membrane. The following
      article addresses the predictive power of the OnGuard model to generate
      unexpected and counterintuitive outputs.

PMID- 22635118
TI  - Examination of the distribution of arsenic in hydrated and fresh cowpea roots
      using two- and three-dimensional techniques.
AB  - Arsenic (As) is considered to be the environmental contaminant of greatest
      concern due to its potential accumulation in the food chain and in humans. Using
      novel synchrotron-based x-ray fluorescence techniques (including sequential
      computed tomography), short-term solution culture studies were used to examine
      the spatial distribution of As in hydrated and fresh roots of cowpea (Vigna
      unguiculata 'Red Caloona') seedlings exposed to 4 or 20 um arsenate [As(V)] or 4
      or 20 um arsenite. For plants exposed to As(V), the highest concentrations were
      observed internally at the root apex (meristem), with As also accumulating in the
      root border cells and at the endodermis. When exposed to arsenite, the endodermis
      was again a site of accumulation, although no As was observed in border cells.
      For As(V), subsequent transfer of seedlings to an As-free solution resulted in a
      decrease in tissue As concentrations, but growth did not improve. These data
      suggest that, under our experimental conditions, the accumulation of As causes
      permanent damage to the meristem. In addition, we suggest that root border cells
      possibly contribute to the plant's ability to tolerate excess As(V) by
      accumulating high levels of As and limiting its movement into the root.

PMID- 22635117
TI  - An A/ENTH domain-containing protein functions as an adaptor for clathrin-coated
      vesicles on the growing cell plate in Arabidopsis root cells.
AB  - Cytokinesis is the process of partitioning the cytoplasm of a dividing cell,
      thereby completing mitosis. Cytokinesis in the plant cell is achieved by the
      formation of a new cell wall between daughter nuclei using components carried in
      Golgi-derived vesicles that accumulate at the midplane of the phragmoplast and
      fuse to form the cell plate. Proteins that play major roles in the development of
      the cell plate in plant cells are not well defined. Here, we report that an AP180
      amino-terminal homology/epsin amino-terminal homology domain-containing protein
      from Arabidopsis (Arabidopsis thaliana) is involved in clathrin-coated vesicle
      formation from the cell plate. Arabidopsis Epsin-like Clathrin Adaptor1 (AtECA1;
      At2g01600) and its homologous proteins AtECA2 and AtECA4 localize to the growing
      cell plate in cells undergoing cytokinesis and also to the plasma membrane and
      endosomes in nondividing cells. AtECA1 (At2g01600) does not localize to nascent
      cell plates but localizes at higher levels to expanding cell plates even after
      the cell plate fuses with the parental plasma membrane. The temporal and spatial
      localization patterns of AtECA1 overlap most closely with those of the clathrin
      light chain. In vitro protein interaction assays revealed that AtECA1 binds to
      the clathrin H chain via its carboxyl-terminal domain. These results suggest that
      these AP180 amino-terminal homology/epsin amino-terminal homology domain
      containing proteins, AtECA1, AtECA2, and AtECA4, may function as adaptors of
      clathrin-coated vesicles budding from the cell plate.

PMID- 22635119
TI  - Pediatric brain injury and recovery.

PMID- 22635120
TI  - The two Janes we knew and loved.

PMID- 22635121
TI  - Self-esteem in children after traumatic brain injury: an exploratory study.
AB  - Children with a traumatic brain injury (TBI) often have difficulties in adjusting
      to their injury and altered abilities, and may be at risk of low self-esteem and
      loss of confidence. However, few studies have examined self-esteem in this client
      group. The current study measured the self-esteem of a group of children who
      were, on average, two years post-TBI and compared this to their performance on
      other psychometric measures. Participants were 96 children with TBI and 31 peer
      controls, their parents and teachers. Self-esteem was measured using the
      Coopersmith Self-esteem Inventory (CSEI). CSEI scores were compared with
      performance on Wechsler Intelligence Scales (WISC-III), Hospital Anxiety and
      Depression Scale (HADS); Children's Memory Scale (CMS), Vineland Adaptive
      Behaviour Scales (VABS) and Parental Stress Index (PSI). Self-esteem was highly
      correlated with IQ; HADS anxiety and depression; and parental stress (p< 0.001).
      Children with TBI had significantly lower self-esteem than controls and
      population norms (p=0.015). Many children with TBI demonstrate low self-esteem
      and this is closely linked with anxiety and depression. This may hamper academic
      performance and could lead to further psychosocial problems. It is recommended
      that self-esteem is routinely assessed after brain injury and rehabilitation
      strategies implemented to promote a sense of self-worth.

PMID- 22635122
TI  - The invisible brain injury: the importance of identifying deficits following
      brain injury in children with intellectual disability.
AB  - INTRODUCTION: Traumatic brain injury (TBI) is common during childhood. However,
      most of the extant literature about outcomes following childhood TBI is based on
      children who were functioning "normally" prior to the injury event. But, with the
      increasing community integration of children with Intellectual Disability (ID)
      there is an urgent need for specific information regarding problems following TBI
      for this group. METHOD: Using a case study, this paper presents an overview of
      problems faced by these children who subsequently experience a TBI event, and
      examines questions pertinent to this dual diagnosis. OUTCOMES: In the case study
      presented, despite supposedly having access to an internationally acclaimed
      comprehensive no fault accident compensation and rehabilitation system, a lack of
      assessment, intervention and support was evident for both the child and the
      family following a severe TBI because he had pre-existing ID. CONCLUSIONS: This
      case study highlights the need for clinicians to consider the impact of TBI for
      children with ID, to avoid incorrectly attributing TBI symptoms to pre-existing
      problems. Children with ID are at increased risk; appropriate treatment plans are
      vital to maximize quality of life for them and their caregivers.

PMID- 22635123
TI  - Feasibility and consumer satisfaction ratings following an intervention for
      families who have a child with acquired brain injury.
AB  - OBJECTIVE: Our objective was to ascertain the feasibility and consumer
      satisfaction ratings of families who received an adapted pediatric acquired brain
      injury (ABI) 'Signposts for Building Better Behavior' program in either group- or
      telephone-support delivery formats. METHODS: Forty-eight families of children
      aged between 3 and 12 years with mild, moderate, and severe ABI completed
      Signposts in group (n=23) or telephone-support (n=25) format consisting of nine
      information booklets, a DVD, and Workbook. RESULTS: All parents approved of the
      skills taught and a majority felt the materials were helpful in both managing
      challenging behavior associated with brain injury, and teaching new skills to
      their brain injured child. All parents rated a high level of feasibility for all
      of the Signposts materials. CONCLUSION: The current research has provided
      preliminary evidence for the feasibility and satisfaction of a family-centered
      parent-based behavioral intervention program called Signposts to be used with a
      pediatric ABI population. It also provides evidence for a less costly option of
      intervention delivery via telephone-support.

PMID- 22635124
TI  - An innovative approach to meeting the educational needs of children following
      acquired brain injury in the UK.
AB  - Children with acquired brain injury encounter problems both in terms of academic
      attainment and in other aspects of their lives in relation to social, behavioural
      and independent life skills. Many previous rehabilitation programmes for these
      children have been inappropriately adapted versions of adult models but there has
      often not been a recognition that successful current adult models of vocational
      rehabilitation can translate to educational rehabilitation models for children
      and adolescents. This article considers the historical basis of provision for
      these children in the UK and describes the development of a new programme of
      education as rehabilitation.

PMID- 22635125
TI  - Empowering preadolescents with ABI through metacognition: preliminary results of
      a randomized clinical trial.
AB  - PURPOSE: The aim of this randomized clinical trial study was to evaluate the
      efficacy of an intervention program based on social mediation, cooperative
      learning and metacognition (Metacognitive Dimension) in preadolescents with
      acquired brain injury (ABI). PARTICIPANTS/METHODS: Participants were 29 ABI
      preadolescents: 14 in the experimental group and 15 in the control group (average
      age, 10.4 y.o.; average time of lesion, 5.3 years). Evaluations were conducted 3
      months after the start of the intervention, using the Evaluation Scale of
      Elementary School Learning Strategies (ESESLS) to assess metacognitive
      strategies, Self-Concept Scale for Children (SCSC) and Behavioral Rating
      Inventory of Executive Functions (BRIEF). RESULTS: The experimental group had
      superior outcomes to the control. The results of metacognitive strategies
      (ESESLS) and self-concept (SCSC) were better in the experimental than in the
      control group (p< 0.05). BRIEF did not reveal any significant differences between
      the groups, although we observed better results in the experimental group for 5
      sub items of the scale, in the broader index and global executive composite
      score. CONCLUSION: Three months of an intervention based on cooperative learning
      helped preadolescents with acquired brain injury develop metacognitive strategies
      and improve self-concept, thereby helping empower the preadolescents in their
      social relationships.

PMID- 22635126
TI  - Caregiver reported problems of children and families 2-4 years following
      rehabilitation for pediatric brain injury.
AB  - In this article we report the results of a small-scale pilot study into the self
      reported problems of children with brain injuries and the unmet needs of their
      families two to four years following rehabilitation in a rehabilitation centre.
      Parents reported a lot of ongoing problems in their children as well as unmet
      family needs. It is concluded that long-term follow-up programs, like the PABICOP
      program, founded by dr. Jane Gillett are necessary to detect and meet the needs
      of these children and families.

PMID- 22635127
TI  - Decompressive craniectomy in pediatric traumatic brain injury: a review of the
      literature.
AB  - BACKGROUND: Pediatric traumatic brain injury accounts for approximately 37,000
      hospitalizations and 2,685 deaths in the United State annually. The 2003
      guidelines consolidated and summarized the body of literature on this subject.
      Among the material covered was the role of surgical management of elevated
      intracranial pressure. Here we review the guideline recommendations, recent
      literature on the topic, and important recent results in the adult population.
      METHODS: A Medline literature review was performed to identify studies published
      since 2000 addressing decompressive craniectomy in the pediatric and adult
      populations. Important articles included in the 2003 guidelines were also
      reviewed. All references were reviewed to identify additional relevant studies.
      RESULTS: There is little new data that addresses the key issues for investigation
      proposed in the 2003 pediatric guidelines. The only randomized trial in the
      pediatric population remains a 2001 study, which demonstrated a benefit of
      decompressive craniectomy. One recent randomized trial in adults demonstrated no
      benefit of the procedure and an additional randomized trial in adults is
      underway. No pediatric randomized trial is planned. Smaller, non-randomized
      series appear to support the practice. CONCLUSION: Based on the only randomized
      trial in children and the abundance of smaller studies, it is our belief that
      decompressive craniectomy does provide a benefit in terms of the management of
      intracranial hypertension and overall outcome in children.

PMID- 22635128
TI  - Medical aspects of pediatric rehabilitation after moderate to severe traumatic
      brain injury.
AB  - Recovery from severe traumatic brain injury (TBI) is prolonged, complicated and
      challenging. Medical rehabilitation is the bridge from acute medical care and
      stabilization to community reintegration. The process of caring for the
      recovering brain introduces unknown challenges of neural plasticity with demands
      to restore and to also move the child and family back to the developmental
      trajectory they once knew. While the ongoing focus is to maintain and advance
      medical stability, co- morbid conditions are addressed, and a plan for ongoing
      health is established. While no one manuscript can cover all of the medical
      aspects, this article will present in a "systems review" manner the most
      challenging and demanding medical conditions that children may confront following
      severe brain injury.

PMID- 22635129
TI  - Factitious torsion dystonia in rehabilitation: a singular new case and literature
      review.
AB  - We report a case of a 29-year-old woman suffering from chronic factitious
      disorder (FD) with torsion dystonia. For nearly five years, she traveled widely
      over the country, going from one hospital to another, taking serious medical risk
      in order to prolong her illness. After several admissions to Rehabilitation Units
      and multiple explorations, we find convincing evidence for factitious origin and
      the diagnosis of Munchausen syndrome was evoked. Such a clinical presentation is
      infrequent in Munchausen's syndrome. Indeed, most often the clinical picture is
      characterized by acute abdominal pain, fainting, hemoptysis, precordialgia,
      hematemesis or dermatological lesions. Physicians should be aware of this rare
      and potentially critical form of FD. Awareness in identifying these patients may
      lead to prevent unnecessary medical and/or surgical interventions.

PMID- 22635130
TI  - Effects of functional task training with mental practice in stroke: a meta
      analysis.
AB  - OBJECTIVE: Meta analysis of studies was carried out to examine the effectiveness
      of functional task training with mental practice on functional performance
      following stroke. SEARCH STRATEGY: An exhaustive search was conducted using
      computerized databases such as MEDLINE, PubMed, Cochrane, PsycINFO, and EBSCO
      (CINAHL). SELECTION CRITERIA: The search was performed using the following
      keywords: stroke, functional task, mental practice, randomized controlled trial.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently retrieved appropriate
      RCTs, extracted data, and assessed the methodological quality of each study.
      Selected studies needed to report the statistical values necessary for
      calculating the effect size, which was estimated using the standardized
      difference of the mean. Statistical heterogeneity and publication bias were also
      investigated. RESULTS: The five studies included 146 participants. The overall
      effect size was moderate (0.51, p < 0.001). The 95% confidence interval was from
      0.27 to 0.75. Significant heterogeneity and publications bias were not founded.
      CONCLUSION: The present study is the first meta-analysis conducted on the
      effectiveness of functional task training with mental practice in stroke. The
      results indicate the clinical effectiveness of functional task training with
      mental practice provided by occupational and physical therapists in stroke
      rehabilitation.

PMID- 22635131
TI  - Gender and stroke lateralization: factors of functional recovery after the first
      ever unilateral stroke?
AB  - PURPOSE: The goal of this prospective study was to evaluate gender differences in
      rehabilitation outcome in patients after the first-ever unilateral stroke.
      METHODS: A total of eighty right-handed patients were prospectively enrolled, 35
      (44%) women, and 45 (56%) men. A degree of neurological deficit was quantified by
      the National Institutes of Health Stroke Scale. Functional outcome was assessed
      by the Motor Status Scale, Chedoke Arm and Hand Activity Inventory, Rivermead
      Mobility Index and Barthel Index. RESULTS: At the time of hospital admission
      there was no significant gender difference in clinical stroke severity. At
      discharge, we registered significantly better motor and functional recovery in
      men compared to women. Further, we found significantly better rehabilitation
      outcome in women with stroke in dominant left hemisphere (LH) than in women with
      stroke in subdominant right hemisphere (RH). Conversely, men with stroke in
      subdominant RH had significantly better rehabilitation outcome than men with
      stroke in dominant LH. Using a multivariate analysis we have found that men with
      stroke in RH had significantly higher probability to reach not only high response
      in mobility, but also more autonomy in ADL. The frequency of stroke in LH was
      significantly higher in both genders aged less than 51 years, as well as in
      women, while the frequency of stroke in RH was significantly higher in men.
      CONCLUSION: This paper places particular emphasis on substantial gender-based
      differences in functional recovery of patients with their first-ever unilateral
      stroke.

PMID- 22635132
TI  - ZnIO3(OH): a new layered noncentrosymmetric polar iodate--hydrothermal synthesis,
      crystal structure, and second-harmonic generating (SHG) properties.
AB  - A new noncentrosymmetric polar iodate material, ZnIO(3)(OH), has been
      hydrothermally synthesized as crystals and pure powders by using ZnO (or
      Zn(CH(3)CO(2))(2).2H(2)O), HIO(3), and water. Single crystal X-ray diffraction
      was used to determine the crystal structure of the reported material. ZnIO(3)(OH)
      exhibits a layered structure that is composed of ZnO(6) and IO(3) polyhedra.
      Powder nonlinear optical (NLO) properties measurements on ZnIO(3)(OH) using 1064
      nm radiation indicate the material has a second-harmonic generating (SHG)
      efficiency of approximately 20 times that of alpha-SiO(2). Additional SHG
      measurements reveal that the material is not phase-matchable (type 1). Infrared
      spectroscopy, elemental analysis, and thermogravimetric analysis for the reported
      compound are also presented. Crystal data: ZnIO(3)(OH), monoclinic, space group
      Cc (no. 9) with a = 4.67670(10) A, b = 11.2392(4) A, c = 6.3308(2) A, beta =
      90.019(2) degrees , and Z = 4.

PMID- 22635133
TI  - The influence of non-covalent interactions on the hydrogen peroxide
      electrochemistry on platinum in alkaline electrolytes.
AB  - The potential range of the transition region between the diffusion-limited
      reduction to oxidation of hydrogen peroxide depends strongly on the nature of the
      cation of the supporting alkaline electrolyte. Non-covalent interactions between
      the hydrated alkali metal cations and chemisorbed OH species on platinum
      influence the potential-dependent reaction kinetics.

PMID- 22635134
TI  - Managing behavior for a child with autism in a body cast.
AB  - CASE: : Elisa is a 6 1/2-year-old white female who has a follow-up appointment in
      the Developmental Clinic where she is seen for autism, developmental delay, and
      significant behavioral problems. Her grandparents, who are her legal guardians,
      request an opinion on a proposed surgery for developmental dysplasia of the hip
      that will require several months in a whole body cast. Reconstruction of the hip
      was recommended by 2 pediatric orthopedic surgeons to prevent later disability
      and pain.Elisa was born following a 41-week gestation. She sat without support at
      7 months, but she did not walk until 23 months of age. An evaluation at the
      Developmental Clinic at 28 months of age documented gross and fine motor delays,
      cognitive impairment, and autism. A karyotype, fragile X, and microarray were
      normal. Elisa has a brother with autism and a maternal cousin with mental
      retardation. After her mother's death from meningitis 2 years ago, her maternal
      grandparents became her legal guardian.Behavior problems include significant
      hyperactivity, impulsivity, and aggressive behaviors. She seldom sits still. She
      also has frequent stereotypies, such as jumping and arm flapping when she is
      excited or upset. Methylphenidate was associated with increased hyperactivity and
      irritability.Physical examination demonstrates that she can walk with a very wide
      gait and swings her right foot out. A magnetic resonance imaging of her brain,
      acoustic brain response audiometry, and metabolic studies are normal. Other
      medical issues include gastroesophageal reflux, recurrent pneumonia, and ear
      infections. Radiographs of the hip reveal a steep acetabulum and a hip that
      easily dislocates. A magnetic resonance imaging of the hip shows early formation
      of a pseudoarthrosis. Her grandparents and pediatrician are concerned about
      managing her behavior after the surgery when she will be in a body cast.

PMID- 22635136
TI  - Investigating the structural evolution of thiolate protected gold clusters from
      first-principles.
AB  - Unlike bulk materials, the physicochemical properties of nano-sized metal
      clusters can be strongly dependent on their atomic structure and size. Over the
      past two decades, major progress has been made in both the synthesis and
      characterization of a special class of ligated metal nanoclusters, namely, the
      thiolate-protected gold clusters with size less than 2 nm. Nevertheless, the
      determination of the precise atomic structure of thiolate-protected gold clusters
      is still a grand challenge to both experimentalists and theorists. The lack of
      atomic structures for many thiolate-protected gold clusters has hampered our in
      depth understanding of their physicochemical properties and size-dependent
      structural evolution. Recent breakthroughs in the determination of the atomic
      structure of two clusters, [Au(25)(SCH(2)CH(2)Ph)(18)](q) (q = -1, 0) and
      Au(102)(p-MBA)(44), from X-ray crystallography have uncovered many new
      characteristics regarding the gold-sulfur bonding as well as the atomic packing
      structure in gold thiolate nanoclusters. Knowledge obtained from the atomic
      structures of both thiolate-protected gold clusters allows researchers to examine
      a more general "inherent structure rule" underlying this special class of ligated
      gold nanoclusters. That is, a highly stable thiolate-protected gold cluster can
      be viewed as a combination of a highly symmetric Au core and several protecting
      gold-thiolate "staple motifs", as illustrated by a general structural formula
      [Au](a+a')[Au(SR)(2)](b)[Au(2)(SR)(3)](c)[Au(3)(SR)(4)](d)[Au(4)(SR)(5)](e) where
      a, a', b, c, d and e are integers that satisfy certain constraints. In this
      review article, we highlight recent progress in the theoretical exploration and
      prediction of the atomic structures of various thiolate-protected gold clusters
      based on the "divide-and-protect" concept in general and the "inherent structure
      rule" in particular. As two demonstration examples, we show that the
      theoretically predicted lowest-energy structures of Au(25)(SR)(8)(-) and
      Au(38)(SR)(24) (-R is the alkylthiolate group) have been fully confirmed by later
      experiments, lending credence to the "inherent structure rule".

PMID- 22635135
TI  - Electricity-free, sequential nucleic acid and protein isolation.
AB  - Traditional and emerging pathogens such as Enterohemorrhagic Escherichia coli
      (EHEC), Yersinia pestis, or prion-based diseases are of significant concern for
      governments, industries and medical professionals worldwide. For example, EHECs,
      combined with Shigella, are responsible for the deaths of approximately 325,000
      children each year and are particularly prevalent in the developing world where
      laboratory-based identification, common in the United States, is unavailable (1).
      The development and distribution of low cost, field-based, point-of-care tools to
      aid in the rapid identification and/or diagnosis of pathogens or disease markers
      could dramatically alter disease progression and patient prognosis. We have
      developed a tool to isolate nucleic acids and proteins from a sample by solid
      phase extraction (SPE) without electricity or associated laboratory equipment
      (2). The isolated macromolecules can be used for diagnosis either in a forward
      lab or using field-based point-of-care platforms. Importantly, this method
      provides for the direct comparison of nucleic acid and protein data from an un
      split sample, offering a confidence through corroboration of genomic and
      proteomic analysis.    Our isolation tool utilizes the industry standard for
      solid-phase nucleic acid isolation, the BOOM technology, which isolates nucleic
      acids from a chaotropic salt solution, usually guanidine isothiocyanate, through
      binding to silica-based particles or filters (3). CUBRC's proprietary solid-phase
      extraction chemistry is used to purify protein from chaotropic salt solutions, in
      this case, from the waste or flow-thru following nucleic acid isolation(4).    By
      packaging well-characterized chemistries into a small, inexpensive and simple
      platform, we have generated a portable system for nucleic acid and protein
      extraction that can be performed under a variety of conditions. The isolated
      nucleic acids are stable and can be transported to a position where power is
      available for PCR amplification while the protein content can immediately be
      analyzed by hand held or other immunological-based assays. The rapid
      identification of disease markers in the field could significantly alter the
      patient's outcome by directing the proper course of treatment at an earlier stage
      of disease progression. The tool and method described are suitable for use with
      virtually any infectious agent and offer the user the redundancy of multi
      macromolecule type analyses while simultaneously reducing their logistical
      burden.

PMID- 22635137
TI  - Getting the message across:  opportunities and obstacles in effective
      communication in hypertension care.
AB  - Effective communication is a prerequisite for any successful encounter between
      patient and provider. Nevertheless, it is unclear how/where communication can
      impact/affect adherence to antihypertensive medication, and maintenance of
      lifestyle changes to control blood pressure targets. Poor physician communication
      is correlated with a higher risk of treatment nonadherence. Given the high rates
      of hypertension globally, this review serves to enlighten aspects of the
      communication exchange from a provider, context, and patient perspective.
      Relevant articles were analyzed to assess barriers, solutions, and optimizations
      for communication with hypertensive patients. To support the findings, a model of
      communication in the context of hypertension treatment is presented, which
      comprises three phases: comprehension and acceptance, translation into action,
      and long-term retention. Secondly, an analysis of care providers (bedside manner,
      verbal/nonverbal communication, empathy and sex, time, knowledge base), context
      (format and tailoring of the message, and physical environment), and patient
      related factors (sex, socio-economic status, language and health literacy,
      culture, age, psychological factors) were assessed in relation to hypertension.
      Current literature is limited regarding reciprocal communication, adaptive
      packaging of messages, and active verification of effective communication. To
      improve communication, hypertension care programs could benefit from better
      communication training, more team-based approaches, and flexible tools based on
      information technology.

PMID- 22635138
TI  - Pulsatile hemodynamics of hypertension:  systematic review of aortic input
      impedance.
AB  - OBJECTIVE: Input impedance is the frequency-dependent afterload to pulsatile
      blood flow. Studies of input impedance have been performed as early as the 1960s
      and have been applied to hypertension (HTN). However, to date, these studies have
      not been systematically evaluated. This systematic review aims to summarize the
      literature, interpret existing data from the perspective of impedance theory, and
      to discuss their potential for generating physiological insights into HTN.
      METHODS: We identified 11 studies wherein computed impedance moduli from both HTN
      and control (CNT) groups were reported. In addition, we performed bivariate
      analyses of raw data from three of these studies. RESULTS: Major findings include
      HTN groups had consistently elevated impedance moduli at 0 Hz (Z(0)) and at heart
      rate frequency (Z(1)), an increased frequency wherein impedance phase first
      crosses 0 (f(0)), but no consistent pattern in characteristic impedance (Z(c)),
      when compared to CNT groups; SBP and DBP are highly correlated with Z(0) and
      Z(1), moderately correlated with f(0), less correlated with Z(c); the measurement
      and calculation methods for Z(c) are varied and inconsistent; and a not
      insignificant proportion of hypertensive individuals have 'normal' Z(0), Z(1) and
      Z(c) values. These findings are limited by the heterogeneous study populations
      and small sample sizes. CONCLUSION: These findings suggest that Z(0), Z(1) and
      f(0) are significantly associated with HTN, whereas the role of Z(c) is less
      clear. Additional studies are needed to evaluate these input impedance variables
      in order to generate substantial implications in clinic settings.

PMID- 22635139
TI  - Brachial artery tonometry and the Popeye phenomenon:  explanation of anomalies in
      generating central from upper limb pressure waveforms.
AB  - BACKGROUND: Noninvasive applanation tonometry studies of the brachial and radial
      artery pressure waves show that the arterial pulse is substantially amplified
      between the brachial and radial sites. Brachial tonometry waveforms have also
      been used to calibrate carotid tonometry waves as a measure of central pressure
      in major clinical trials. These trials assume identity of mean and of DBP in
      calculation of central (carotid) SBP. None of these trials showed superiority of
      central over brachial pressure in predicting outcome, but all showed equivalence
      of SBP and pulse pressure at brachial and carotid sites! METHOD: We tested this
      method by measuring pressure waves at brachial, radial and carotid sites by
      applanation tonometry in 100 patients, with attention to any subtle difference
      between brachial and radial waveforms, and with both calibrated to cuff SBP and
      DBP. RESULTS: The results confirmed no proximal and strong distal amplification
      in the arm. However, this was accompanied by blunting of the brachial compared
      with radial waveform with brachial pressure 2.7 mmHg higher during most of the
      cardiac cycle. Form factor of the ensemble-averaged brachial wave [39.1 standard
      deviation (SD) 4.9%] was similar to the carotid (40.2 SD 4.1%) but different to
      the radial wave (34.8 SD 3.7%; P < 0.01). CONCLUSIONS: All findings were
      explained by inability to applanate the brachial artery, and resulting systematic
      error in generating brachial waveforms. In estimation of central pressure with
      applanation tonometry, the radial pressure wave, which can be accurately
      applanated, should be used, and calibrated to the brachial cuff.

PMID- 22635140
TI  - Central and peripheral blood pressure profile of young offspring with
      hypertensive and normotensive parents.
AB  - OBJECTIVES: In this cross-sectional study we compared the central aortic systolic
      pressure (CASP), peripheral brachial systolic pressure (PSP), peripheral brachial
      diastolic pressure (PDP) and augmentation index (AIx) between normotensive
      offspring of nonhypertensive parents (ONT) and normotensive offspring with at
      least one hypertensive parent (OHT). METHODOLOGY: A total of 100 healthy ONT
      (mean age 20.95 +/- 2.06) and 100 healthy OHT (mean age 20.89 +/- 2.12)
      individuals were recruited. Parental history of hypertension was determined by
      detailed history taking. CASP, PSP, PDP and AIx were measured using the BPro
      device. All blood pressure (BP) measurements were calibrated using oscillometric
      BP readings. RESULTS: The OHT group had higher PSP (117.57 +/- 10.06 versus
      114.52 +/- 8.94, P < 0.05), PDP (72.39 +/- 7.28 versus 70.39 +/- 6.50, P < 0.05)
      and CASP (103.72 +/- 8.95 versus 101.37 +/- 7.74, P < 0.05) compared to the ONT
      group. There was no significant difference in AIx in the ONT group (57.97 +/-
      11.02 versus 58.08 +/- 12.16, P = 0.95) in comparison to the OHT group. However,
      following adjustments for certain cardiovascular risk factors, only PSP (117.33
      versus 114.76, P < 0.05) remained significantly higher in the OHT group compared
      to the ONT group. Analysis of adjusted data within sex showed that CASP was
      higher in the female OHT group compared to the female ONT group, whereas PDP were
      higher in the male OHT group compared to the male ONT group. CONCLUSION:
      Alterations in PSP, PDP and CASP are already present in early life in
      normotensive offspring of hypertensive parents, with possible differences in
      mechanism between different sexes.

PMID- 22635141
TI  - Workplace violence and aggression. Foreword.

PMID- 22635143
TI  - Workplace violence and the media: the myth of the disgruntled employee.

PMID- 22635144
TI  - An integrative approach to threat assessment and management: security and mental
      health response to a threatening client.
AB  - Workplace violence threat assessment and management practices represent an
      interdisciplinary approach to the diversion of potentially dangerous employees
      and clients. This case study illustrates such an intervention in a complex
      situation involving a social service agency and its client. Following a
      curtailment of services and an arrest, the client developed an escalating
      homicidal anger toward the agency administrator. Once a Tarasoff warning was
      received, the agency contacted a security company who organized a threat
      assessment and management plan involving interdisciplinary collaboration.
      Information developed in the course of the assessment was presented to
      prosecutors, who facilitated the client's arrest and involuntary psychiatric
      commitment until he was judged to be no longer dangerous. This case ultimately
      involved an integration of the services of security, law enforcement, mental
      health professionals, prosecutors, the courts and the state mental health system
      in leading to a successful diversion of the client from a path of intended
      violence.

PMID- 22635145
TI  - Workplace violence: impact, causes, and prevention.
AB  - OBJECTIVES: Using a variety of sources, the author explores the complex reasons
      for aggression and violence in workplace settings, as well as suggesting means of
      prevention and intervention. METHODS: Literature Review. RESULTS: Studies
      indicate workplace violence affects more than half of U.S. organizations, yet
      nearly 70 percent have no programs or policies to deal with this problem.
      Research indicates that aggressive behavior of a psychological nature often
      precedes physical violence in the workforce, yet employers regularly ignore
      warning signs even when reported by employees. Costs to U.S. employers are
      estimated in the millions due to employee absences, medical costs, theft, and
      costs related to litigation. CONCLUSIONS: Organizations with cultures which
      support fair working conditions and zero-tolerance for workplace aggression have
      been shown to help mitigate workplace violence.

PMID- 22635146
TI  - Emergency department workers' perceptions of security officers' effectiveness
      during violent events.
AB  - OBJECTIVE: The emergency department (ED) is among the most at-risk settings for
      violence by patients and visitors against ED workers. A first response to
      potential or actual events of workplace violence is often contacting hospital
      security officers for assistance. The purpose of this study is to describe ED
      workers' views of security officers' effectiveness during actual events of verbal
      and/or physical violence. PARTICIPANTS: Healthcare workers (n=31) from an urban
      pediatric ED in the Midwest United States. METHODS: Participants were interviewed
      regarding their experiences with workplace violence. Verbatim transcripts were
      qualitatively analyzed. RESULTS: Six themes were identified: (1) a need for
      security officers, (2) security officers' availability and response, (3) security
      officers' presence or involvement, (4) security officers' ability to handle
      violent situations, (5) security officers' role with restraints, and (6) security
      officers' role with access. CONCLUSIONS: It is important that early communication
      between security officers and ED workers takes place before violent events occur.
      A uniform understanding of the roles and responsibilities of security officers
      should be clearly communicated to ED workers. Future research needs to be
      conducted with hospital-based security officers to describe their perceptions
      about their role in the prevention and management of workplace violence.

PMID- 22635147
TI  - Safety climate and verbal abuse among public hospital-based workers in Costa
      Rica.
AB  - OBJECTIVE: Low levels of safety climate and training have been associated with
      higher occurrence of occupational-related health outcomes; workplace violence and
      verbal abuse could be considered an early indicator of escalating psychological
      workplace violence. We examined whether low level of safety factors were
      associated with a higher prevalence of verbal abuse at the workplace. METHODS: We
      used data from a cross-sectional survey administered among a stratified random
      sample of 1,000 employees from 10 of the 29 public hospitals in Costa Rica. Odds
      ratios (OR) and 95% confidence intervals (95%CI) were calculated using survey
      logistic regression models to estimate the association between safety factors and
      verbal abuse from the following sources: administrators, supervisors, patients,
      patients' relatives and coworkers. RESULTS: There was a high prevalence of verbal
      abuse among the healthcare workforce from both external (i.e., patients and
      patients' relatives) and internal workplace sources (i.e., coworkers, supervisors
      and administrators). A low level of safety climate was associated with verbal
      abuse from all sources with associations ranging from verbal abuse from
      administrators (OR=6.07; 95%CI: 2.05-17.92) to verbal abuse from patients
      (OR=2.24; 95%CI: 1.23-4.09). CONCLUSION: These results highlight the need to
      address organizational characteristics of the workplace that may increase the
      risk of verbal abuse for the future development of prevention interventions in
      this setting.

PMID- 22635148
TI  - Risk of physical assault against school educators with histories of occupational
      and other violence: a case-control study.
AB  - A case-control study design was used to investigate risks of work-related
      physical assault (PA) associated with a history of violent victimization among
      educators. A total of 6,469 state-licensed educators (Kindergarten - Grade 12)
      worked in the previous 12~months and were eligible to participate. Exposure data
      were collected from cases (reporting a PA event in previous 12 months, n=290) for
      the month before PA, and from controls (no work-related PA in previous 12 months;
      n=867) for a randomly selected working month. Odds ratios and 95% confidence
      intervals identified increased risks for educators with any prior history of work
      related (17.3, 11.4-26.3) or non-work-related PA (2.0, 1.2-3.5). In addition, PA
      risk in the previous twelve months increased with the number of previous
      victimizations, and risk also increased for educators with histories of non
      physical violence (work- and non work-related). The results present a compelling
      case for targeted interventions and further research.

PMID- 22635149
TI  - Safety climate and workplace violence prevention in state-run residential
      addiction treatment centers.
AB  - OBJECTIVE: To examine the association between violence prevention safety climate
      measures and self reported violence toward staff in state-run residential
      addiction treatment centers. METHODS: In mid-2006, 409 staff from an Eastern
      United States state agency that oversees a system of thirteen residential
      addiction treatment centers (ATCs) completed a self-administered survey as part
      of a comprehensive risk assessment. The survey was undertaken to identify and
      measure facility-level risk factors for violence, including staff perceptions of
      the quality of existing US Occupational Safety and Health Administration (OSHA)
      program elements, and ultimately to guide violence prevention programming. Key
      informant interviews and staff focus groups provided researchers with qualitative
      data with which to understand safety climate and violence prevention efforts
      within these work settings. RESULTS: The frequency with which staff reported
      experiencing violent behavior ranged from 37% for "clients raised their voices in
      a threatening way to you" to 1% for "clients pushed, hit, kicked, or struck you".
      Findings from the staff survey included the following significant predictors of
      violence: "client actively resisting program" (OR=2.34, 95% CI=1.35, 4.05),
      "working with clients for whom the history of violence is unknown" (OR=1.91, 95%
      CI=1.18, 3.09) and "management commitment to violence prevention" reported as
      "never/hardly ever" and "seldom or sometimes" (OR=4.30 and OR=2.31 respectively),
      while controlling for other covariates. CONCLUSIONS: We utilized a combination of
      qualitative and quantitative research methods to begin to describe the risk and
      potential for violence prevention in this setting. The prevalence of staff
      physical violence within the agency's treatment facilities was lower than would
      be predicted. Possible explanations include the voluntary nature of treatment
      programs; strong policies and consequences for resident behavior and ongoing
      quality improvement efforts. Quantitative data identified low management
      commitment to violence prevention as a significant predictor of staff reported
      violence.

PMID- 22635150
TI  - Safe and secure at work?: findings from the 2002 Workplace Risk Supplement.
AB  - OBJECTIVE: To examine employee's perception of safety and related workplace
      safety and prevention issues, including their use of self-protection measures and
      victimization experience. PARTICIPANTS: The Workplace Risk Supplement (WRS) to
      the National Crime Victimization Survey (NCVS) was administered to 55,158
      employed respondents who were 16 years or older. METHODS: Trained U.S. Census
      Bureau interviewers administered the WRS in all households selected for the NCVS
      during the 6-month reference period from January through June 2002. Responses
      from the 55,158 WRS respondents were weighted to obtain national estimates,
      resulting in 142,410,858 cases. RESULTS: The demographic distribution of WRS
      respondents is very similar to that of the U.S. labor force. Seven percent of
      respondents reported that they worried about someone in their workplace attacking
      them, while nearly 4% experienced victimization. The majority indicated that they
      felt that their workplace, the neighborhood around their workplace, and places
      they traveled to as part of their job were either "Very Safe" or "Somewhat Safe"
      from crime. Six percent carried some type of self protection while at work
      although this varied by occupation. CONCLUSIONS: Employees largely feel safe from
      violence while working. Differences in victimization by occupation bolster
      efforts to focus workplace violence prevention in high-risk occupations.

PMID- 22635151
TI  - Evaluating progress in reducing workplace violence: trends in Washington State
      workers' compensation claims rates, 1997-2007.
AB  - OBJECTIVES: This study reports trends in the pattern of injuries related to
      workplace violence over the period 1997-2007. It tracks occupations and
      industries at elevated risk of workplace violence with a special focus on the
      persistently high claims rates among healthcare and social assistance workers.
      METHODS: Industry and occupational incidence rates were calculated using workers'
      compensation and employment security data from Washington State. RESULTS:
      Violence-related claims rates among certain Healthcare and Social Assistance
      industries remained particularly high. Incidents where workers were injured by
      clients or patients predominated. By contrast, claims rates in retail trade have
      fallen substantially. CONCLUSIONS: Progress to reduce violence has been made in
      most of the highest hazard industries within the Healthcare and Social Assistance
      sector with the notable exception of psychiatric hospitals and facilities caring
      for the developmentally disabled. State legislation requiring healthcare
      workplaces to address hazards for workplace violence has had mixed results.
      Insufficient staffing, inadequate violence prevention training and sporadic
      management attention are seen as the key barriers to violence prevention in
      healthcare/social assistance workplaces.

PMID- 22635152
TI  - Associations between sickness absence and harassment, threats, violence, or
      discrimination: a cross-sectional study of the Swedish Police.
AB  - OBJECTIVE: To study if sick leave among employees in the Swedish Police was
      associated with experiences of discrimination, harassment, or (threats of)
      violence. PARTICIPANTS: All employees in the Swedish Police in 2005. METHODS:
      Analyses of data from a questionnaire to all employees; 74% (n=16,725) responded.
      Odds ratios (OR) with 95% confidence intervals (CI) between sick leave and the
      studied factors were assessed. RESULTS: The rate of sickness absence was higher
      for women (12%) than for men (8%) (p< 0.001). More women than men had experienced
      discrimination, while more men reported harassment from the public and
      experiences of threats or violence. ORs were significant between sick-leave and
      discrimination, sexual harassment, and violence, and higher for the men.
      Associations between harassment from the public, threats of violence or violence,
      and sickness absence were statistically significant for men only. CONCLUSION: The
      study identifies the importance of investigating discrimination, harassment, and
      violence in relation to health outcomes for both male and female Police
      employees.

PMID- 22635153
TI  - Workplace hostility: defining and measuring the occurrence of hostility in the
      workforce.
AB  - OBJECTIVES: The purpose of this study was to define a comprehensive construct,
      workplace hostility, encompassing sub-areas of harmful workplace behaviors. Key
      characteristics include: perception of the target, persistence, intentionality,
      nonphysical nature, and organizational affiliation. PARTICIPANTS: Pilot study
      participants (N=42, students and N=35, workers) were small convenience samples.
      Main study participants (N=393, 70% female) were working individuals and almost
      50% reported 1 to 5 years in their current jobs. METHODS: The two pilot studies
      collected were surveys face-to-face. The main study used on-line surveys.
      RESULTS: Based on the pilot studies, items from the Workplace Hostility Inventory
      (WHI) were judged as a reasonable set. Results from the main study suggested
      three subscales related to perceptions of being subjected to hostility:
      interference with work, denigration, and exclusion. Supervisors produced greater
      distress on all factors, but only exclusion predicted a desire to leave the
      organization. Distress was greater when the perpetrator was a woman or a group.
      After controlling for feelings toward coworkers and supervisors, WHI was not
      related to job satisfaction. CONCLUSIONS: The WHI was found to be an inclusive
      construct, representing numerous concepts. The WHI is comprehensive and global,
      encompassing the previous overlap in existing research.

PMID- 22635154
TI  - Engaging men and women as allies: a workplace curriculum module to challenge
      gender norms about domestic violence, male bullying and workplace violence and
      encourage ally behavior.
AB  - This post-hoc analysis discusses a replicable workplace behavior change module
      called Men and Women As Allies, that was designed and implemented by a team of
      labor, management and community anti-violence educators at a private sector
      telecommunications employer. A job site-specific educational seminar linked
      issues of domestic violence to male bullying and workplace violence. It
      challenged social stereotypes about gender, taught skills to engage ally peer
      behavior and provided information on how to seek assistance from union, workplace
      and external community resources.

PMID- 22635155
TI  - Social workers and workplace bullying: perceptions, responses and implications.
AB  - OBJECTIVE: This non-experimental, cross-sectional study examined social workers'
      perceptions of bullying work relationships and their ability to construct
      effective coping responses to perceived workplace bullying. METHODS: Quantitative
      data were gathered through the use of a mailed questionnaire, and qualitative
      data resulted from semi-structured individual interviews. PARTICIPANTS: The
      quantitative sample consisted of 111 social workers from the metropolitan,
      Washington, DC area, who were employed in organizations. Two self-identified
      targets of bullying participated in the interviews. RESULTS: Nearly three of five
      social workers (58%) in the sample reported being the targets of demeaning, rude,
      and hostile workplace interactions more than once in the previous year. Targets
      were more likely to work in government agencies/military and mental health
      outpatient organizations (19% and 18% respectively). More than a third of targets
      (35%) held a direct service role (clinical/direct practice), whereas almost a
      third (29%) identified their role as administration or management. CONCLUSION:
      The findings from this study suggest that workplace bullying may be a problem for
      social workers and that the social work profession may need to develop tools and
      guidelines to help practitioners identify, confront and extinguish these
      behaviors.

PMID- 22635156
TI  - Non-fatal workplace violence injuries in the United States 2003-2004: a follow
      back study.
AB  - OBJECTIVE: Contribute to the prevention of workplace violence by providing
      information about the nature and circumstances of nonfatal assaults among U.S.
      workers. METHODS: Data were collected from the National Electronic Injury
      Surveillance System occupational supplement (NEISS-Work), a stratified
      probability sample of U.S. hospitals. Workplace violence victims identified from
      NEISS-Work voluntarily completed a followback interview detailing the nature and
      circumstances surrounding their workplace violence incident. RESULTS: The
      majority of workplace violence injuries treated in emergency departments resulted
      from simple assaults that did not involve any lost time from work. Almost two
      thirds of these workplace violence victims filed only an internal report. Eighty
      percent of the victims returned to their same jobs and will not change the way
      they do their jobs as a result of the violent incident. CONCLUSIONS: Nonfatal
      workplace violence is an important risk for U.S. workers, particularly in some
      occupations and industries. Prevention strategies need to be tailored by
      occupation and work environment. Results from the healthcare section of this
      survey indicate high numbers of incidents during times when the healthcare
      workers were assisting patients with medical and non-medical needs.

PMID- 22635157
TI  - Social organization and social ties: their effects on sexual harassment
      victimization in the workplace.
AB  - OBJECTIVE: Despite work organizations' attempts to reduce sexual harassment, it
      continues to be a salient issue for employers across all occupations. Extending
      social disorganization theory to the work environment, this study examines the
      relationship between workplace organization, social ties, and sexual harassment
      victimization. PARTICIPANTS: Survey responses to the 2002 and 2006 Quality of
      Working Life module from the General Social Survey by a sample of 3,530 adult men
      and women employees in the United States were used. METHODS: Logistic regression
      models were estimated for men and women separately to estimate the effect of
      workplace characteristics on the risk of sexual harassment victimization.
      RESULTS: Employees who reported poor workplace relations between management and
      employees and lower coworker social ties were more likely to experience sexual
      harassment in their work environments. Specific workplace characteristics such as
      low productivity, poor time management, and inadequate administrative support
      were significantly related to increased sexual harassment risk. No significant
      gender differences were found across models suggesting that the predictors of
      sexual harassment are similar for men and women. CONCLUSIONS: This study
      demonstrates that workplace characteristics are related to sexual harassment risk
      in the workplace. Suggestions for sexual harassment prevention, including
      management and organizational strategies, are discussed.

PMID- 22635158
TI  - Sonochemical synthesis of highly fluorescent glutathione-stabilized Ag
      nanoclusters and S2- sensing.
AB  - A facile one-pot sonochemical approach is presented to prepare highly blue
      emitting Ag nanoclusters (AgNCs) using glutathione as a stabilizing agent in
      aqueous solution. The as-prepared AgNCs can be applied in the selective detection
      of S(2-) with a limit of detection of 2 nM based on fluorescence quenching.

PMID- 22635159
TI  - Dietary fats may impact semen quantity and quality.

PMID- 22635160
TI  - Circumcision reduces prostate cancer risk.

PMID- 22635161
TI  - Derivation of male germ cells from induced pluripotent stem (iPS) cells: a novel
      and crucial source for generating male gametes.

PMID- 22635162
TI  - Characterisation of the bacterial community in expressed prostatic secretions
      from patients with chronic prostatitis/chronic pelvic pain syndrome and infertile
      men: a preliminary investigation.
AB  - The expressed prostatic secretions (EPSs) of men with chronic prostatitis/chronic
      pelvic pain syndrome (CP/CPPS), infertile men and normal men were subjected to
      microbiological study. EPSs were collected from the subjects, which included 26
      normal men, 11 infertile patients and 51 CP/CPPS patients. DNA was extracted from
      each specimen, and the V3 regions of the 16S rRNA genes were amplified using
      universal bacterial primers. The results showed that the EPS 16S rRNA gene
      positive rate in the CP/CPPS and infertile patients was much higher than in the
      normal men, but without any difference among the three patient groups. The
      denaturing gradient gel electrophoresis (DGGE) method was used to characterize
      the EPS bacterial community structure of the prostate fluid from patients with
      CP/CPPS or infertility issues. Principal component analysis (PCA) and partial
      least squares (PLS) analyses of PCR-DGGE profiles revealed that the EPS bacterial
      community structure differed among the three groups. Three bands were identified
      as the key factors responsible for the discrepancy between CP/CPPS patients and
      infertile patients (P<0.05). Two bands were identified as priority factors in the
      discrepancy of category IIIA and category IIIB prostatitis patients (P<0.05).
      According to this research, the ecological balance of the prostate and low
      urethra tract, when considered as a microenvironment, might play an important
      role in the maintenance of a healthy male reproductive tract.

PMID- 22635163
TI  - COX-2 inhibitors in prostate cancer treatment--hold your horses?

PMID- 22635165
TI  - Host response: Destructive interference in immunity.

PMID- 22635164
TI  - Effect of long-acting testosterone undecanoate treatment on quality of life in
      men with testosterone deficiency syndrome: a double blind randomized controlled
      trial.
AB  - This study aimed to investigate the effect of intramuscular injection of
      testosterone undecanoate on overall quality of life (QoL) in men with
      testosterone deficiency syndrome (TDS). A randomized controlled trial over a 12
      month period was carried out in 2009. One hundred and twenty men aged 40 years
      and above with a diagnosis of TDS (serum total testosterone <12 nmol l(-1) and
      total Aging Male Symptom (AMS) scores >=27) were invited to participate.
      Interventions comprised intramuscular injection of either placebo or 1000 mg
      testosterone undecanoate, given at weeks 0, 6, 18, 30 and 42. This paper presents
      the secondary analysis of QoL changes measured in the scores of Short-Form-12 (SF
      12) scale at baseline, weeks 30 and 48 after the first injection. A total of
      56/60 and 58/60 men from the active treatment and placebo group, respectively,
      completed the study. At week 48, before adjusting for baseline differences, the
      QoL of men in the treatment group improved significantly in five out of the eight
      domains on SF-12. The physical health composite scores improved 4.0 points from a
      baseline of 41.9+/-7.0 in the treatment group compared to 0.8 point from a
      baseline of 43.7+/-7.1 in the placebo group (F=3.652, P=0.027). The mental health
      composite scores improved 4.4 points from a baseline of 37.1+/-9.0 in the
      treatment group compared to 1.0 points from a baseline of 37.6+/-7.9 in the
      placebo group (F=4.514, P=0.018). After adjusting for baseline differences,
      significant improvement was observed in mental health composite scores, but not
      in physical health composite scores. Long-acting testosterone undecanoate
      significantly improved the mental health component of QoL in men with TDS.

PMID- 22635167
TI  - The use of acetazolamide during pregnancy in intracranial hypertension patients.
AB  - BACKGROUND: Acetazolamide is the mainstay of medical therapy for idiopathic
      intracranial hypertension (IIH). Its use in pregnant women has not been
      recommended because of reported teratogenic effects in rodents and rabbits.
      However, the safety of acetazolamide use during human pregnancy remains unclear.
      We report the pregnancy and offspring outcomes in women with intracranial
      hypertension (IH) treated with acetazolamide during pregnancy. METHODS: Data were
      collected through questionnaires sent to patients with IH and their physicians.
      The questionnaires focused on IH diagnosis, obstetric history and outcomes, and
      pediatric outcomes. RESULTS: A total of 101 women with IH were consented (total
      of 158 pregnancies) and acetazolamide usage before 13 weeks of gestation was
      reported in 50 pregnancies. The risk of spontaneous abortion was similar to the
      control group and no major complication was identified in the offspring of women
      treated with acetazolamide. CONCLUSION: There is no convincing evidence for an
      adverse effect for acetazolamide use in human pregnancy, even when prescribed
      prior to the 13th week of gestation. While the liberal use of acetazolamide
      should be avoided during pregnancy, this medication should remain a treatment
      option in pregnant women when clinically indicated.

PMID- 22635166
TI  - Neuronal programmed cell death-1 ligand expression regulates retinal ganglion
      cell number in neonatal and adult mice.
AB  - OBJECTIVES: During mouse retina maturation, the final number of retinal ganglion
      cells (RGCs) is determined by highly regulated programmed cell death. Previous
      studies demonstrated that the immunoregulatory receptor programmed cell death-1
      (PD-1) promotes developmental RGC death. To identify the functional signaling
      partner(s) for PD-1, we identified retinal expression of PD-1 ligands and
      examined the effect of PD-1 ligand expression on RGC number. We also explored the
      hypothesis that PD-1 signaling promotes the development of functional visual
      circuitry. METHODS: Characterization of retinal and brain programmed cell death-1
      ligand 1 (PD-L1) expression were examined by immunofluorescence on tissue
      sections. The contribution of PD-ligands, PD-L1, and programmed cell death-1
      ligand 2 (PD-L2) to RGC number was examined in PD-ligand knockout mice lacking 1
      or both ligands. Retinal architecture was assessed by spectral-domain optical
      coherence tomography, and retinal function was analyzed by electroretinography in
      wild-type and PD-L1/L2 double-deficient mice. RESULTS: PD-L1 expression is found
      throughout the neonatal retina and persists in adult RGCs, bipolar interneurons,
      and Muller glia. In the absence of both PD-ligands, there is a significant
      numerical increase in RGCs (34% at postnatal day 2 [P2] and 18% in adult), as
      compared to wild type, and PD-ligands have redundant function in this process.
      Despite the increased RGC number, adult PD-L1/L2 double-knockout mice have normal
      retinal architecture and outer retina function. CONCLUSION: This study
      demonstrates that PD-L1 and PD-L2 together impact the final number of RGCs in
      adult mice and supports a novel role for active promotion of neuronal cell death
      through PD-1 receptor-ligand engagement.

PMID- 22635168
TI  - Unexpected formation of a cyclic vinylene sulfate in the synthesis of ethynyl
      substituted acenes.
AB  - (E)-2-Styrylanthracene derivatives containing triisopropylsilylacetylene groups
      at the 9 and 10 positions were synthesized and characterized. The electronic
      properties have been studied by DFT calculations, spectroscopy and
      electrochemistry, revealing asymmetric resonance stabilization effects that
      result in the regioselective formation of an unusual cyclic vinylene sulfate.

PMID- 22635169
TI  - The bonding in thiolate protected gold nanoparticles from Au4f photoemission core
      level shifts.
AB  - Density functional theory calculations are used to evaluate Au4f core level
      shifts of methyl thiolate protected Au(25), Au(102) and Au(144) nanoparticles.
      The shifts are found to provide sensitive fingerprints of the chemical
      environment. In particular, Au atoms in protective gold-thiolate complexes have
      higher binding energies than Au atoms with solely metal neighbors. The core level
      shifts for the nanoparticles are compared to the corresponding results for methyl
      thiolates adsorbed on Au(111) and implications for the understanding of the gold
      sulfur bond is discussed.

PMID- 22635170
TI  - Compton spectroscopy for rotation-mode computed tomography.
AB  - In computed tomography (CT) systems, it is desirable to know the X-ray energy
      spectra for various applications, including medical CT imaging, and diagnostic
      field and heavy ion therapy. However, because of the restricted space, the only
      practical solution is to use Compton spectroscopy, where the incident spectrum is
      inferred from the scattered spectrum. The geometry of the scatterer and its
      position within the CT can affect the spectrum of the secondary beam, making it
      difficult to determine the primary spectrum during operation of the CT system. A
      modified Compton spectrometer is described that allows measurement of the X-ray
      energy spectra during operation, and most importantly, in rotation mode. The
      geometry of the scatterer was optimized to reduce the energy broadening of the
      secondary beam. The performance of the system was evaluated by comparing the
      reconstructed exposure to that measured directly using an ion chamber.

PMID- 22635171
TI  - Correlation and support vector machine based motion artifacts mitigation in 3D
      computer tomography.
AB  - Head motion during Computer Tomographic (CT) studies can adversely affects the
      reconstructed image through distortion and other artifacts such as blurring and
      doubling, thereby contributing to misdiagnosis of diseases. In this paper, we
      propose a method to detect and mitigate motion artifacts in three-dimensional
      (3D) cone-beam CT system. Motion detection is achieved by comparing the
      correlation coefficient between the adjacent x-ray projections. Artifacts, caused
      by motion, are mitigated either by replacing motion corrupted projections with
      their counterpart 180 degrees  apart projections under certain conditions, or by
      estimating motion corrupted projections using Least Square Support Vector Machine
      (LS-SVM) based time series prediction. The method has been evaluated on 3D Shepp
      Logan phantom. In this research, Feldkamp-David-Kress (FDK) based back-projection
      algorithm is used for 3D reconstruction process. Computer simulation validates
      the motion detection and artifacts elimination mechanism.

PMID- 22635172
TI  - A compensating system of respiratory motion for tumor tracking: design and
      verification.
AB  - Using the reverse motion of the treatment couch, this study offset the organ
      displacement generated by respiratory motion to solve the current clinical
      problem of increasing field sizes and safety margin expansions. This study used
      the self-designed simulated respiratory system (SRS) coupled with radiochromic
      EBT film to verify the self-developed respiratory compensation system. Pressure
      signals were generated from SRS to simulate abdomen movements during respiratory
      motion. The respiratory compensation system takes the phase of the pressure
      signals as the respiratory motion phase and adjusts the pressure signal gain to
      make the compensation signal amplitude close to the displacement of the target
      region. A linear accelerator is used to irradiate a 300 cGy dose on the EBT film.
      The experimental results suggested that the average dose percentage in the target
      region for the sine-wave amplitudes of 5, 10 and 15 mm with compensation improved
      by 6.9 ~ 20.3% over the cases without compensation. The 80% isodose area with
      compensation improved by 22.8 ~ 77.2% over the cases without compensation. The
      average dose percentage in the target region with compensation for respiratory
      motion distances of 5, 10 and 15 mm improved by 10.3 ~ 18.7%. The 80% isodose
      area improved by 22.4 ~ 55.1% after compensation. The average dose percentage of
      the compensated target region indicates that the proposed respiratory
      compensation system could improve the issue of the inability to constantly
      irradiate the target region caused by respiratory motion.

PMID- 22635173
TI  - Mineralogical and morphological investigation of kidney stones of a Mediterranean
      region (Basilicata, Italy).
AB  - Kidney stones are a very frequent finding in southern Italy, but stone analysis
      is not routinely performed. However, it is an important requirement not only for
      a successful treatment of this disease, but also for the prophylaxis to prevent
      any recurrence. We therefore set out to analyze 80 kidney stones collected from
      Basilicata Region (Southern, Italy). X-ray powder diffraction as well as optical
      and scanning electron microscopy and petrographic thin section analysis have been
      applied in order to determine the mineralogical and morphological compositions.
      The internal structure and the relation between major and minor components have
      facilitated the classification of the kidney stones according to a detailed
      scheme. As it is known from other country, calcium oxalate stones were the most
      frequent (59%) [39% mainly composed of whewellite, CaC2O4*H2O and 29% is mainly
      made of weddellite, CaC2O4*2H2O]. Uric acid stones were abundant too (18%).
      Calcium phosphate and cystine stone were less. The results of the observations of
      kidney stones in thin petrographic sections led to the identification of more
      cores in the same whewellite kidney stones. In some kidney stones the core is not
      situated in the central zone, which represents the point of attachment on kidney
      wall. Basilicata kidney stone prevalence is different from the average prevalence
      determined in other Mediterranean areas. The comparison showed that calcium
      oxalate stones seem to be more frequent, and there is a high prevalence of uric
      acid kidney stones and a lower prevalence of phosphate kidney stones, especially
      hydroxyapatite. The relative increase frequency of uric acid stones in the
      northern part of the Region may be due to high-purine diets and softness water
      consumption.

PMID- 22635174
TI  - A multi-thread scheduling method for 3D CT image reconstruction using multi-GPU.
AB  - As a whole process, we present a concept that the complete reconstruction of CT
      image should include the computation part on GPUs and the data storage part on
      hard disks. From this point of view, we propose a Multi-Thread Scheduling (MTS)
      method to implement the 3D CT image reconstruction such as using FDK algorithm,
      to trade off the computing and storage time. In this method we use Multi-Threads
      to control GPUs and a separate thread to accomplish data storage, so that we make
      the calculation and data storage simultaneously. In addition, we use the 4
      channel texture to maintain symmetrical projection data in CUDA framework, which
      can reduce the calculation time significantly. Numerical experiment shows that
      the time for the whole process with our method is almost the same as the data
      storage time.

PMID- 22635175
TI  - Preliminary experimental results from a MARS Micro-CT system.
AB  - The Medipix All Resolution System (MARS) system is a commercial spectral/multi
      energy micro-CT scanner designed and assembled by the MARS Bioimaging, Ltd. in
      New Zealand. This system utilizes the state-of-the-art Medipix photon-counting,
      energy-discriminating detector technology developed by a collaboration at
      European Organization for Nuclear Research (CERN). In this paper, we report our
      preliminary experimental results using this system, including geometrical
      alignment, photon energy characterization, protocol optimization, and spectral
      image reconstruction. We produced our scan datasets with a multi-material
      phantom, and then applied ordered subset-simultaneous algebraic reconstruction
      technique (OS-SART) to reconstruct images in different energy ranges and
      principal component analysis (PCA) to evaluate spectral deviation among the
      energy ranges.

PMID- 22635176
TI  - A novel material detection algorithm based on 2D GMM-based power density function
      and image detail addition scheme in dual energy X-ray images.
AB  - Material detection is a vital need in dual energy X-ray luggage inspection
      systems at security of airport and strategic places. In this paper, a novel
      material detection algorithm based on statistical trainable models using 2
      Dimensional power density function (PDF) of three material categories in dual
      energy X-ray images is proposed. In this algorithm, the PDF of each material
      category as a statistical model is estimated from transmission measurement values
      of low and high energy X-ray images by Gaussian Mixture Models (GMM). Material
      label of each pixel of object is determined based on dependency probability of
      its transmission measurement values in the low and high energy to PDF of three
      material categories (metallic, organic and mixed materials). The performance of
      material detection algorithm is improved by a maximum voting scheme in a
      neighborhood of image as a post-processing stage. Using two background removing
      and denoising stages, high and low energy X-ray images are enhanced as a pre
      processing procedure. For improving the discrimination capability of the proposed
      material detection algorithm, the details of the low and high energy X-ray images
      are added to constructed color image which includes three colors (orange, blue
      and green) for representing the organic, metallic and mixed materials. The
      proposed algorithm is evaluated on real images that had been captured from a
      commercial dual energy X-ray luggage inspection system. The obtained results show
      that the proposed algorithm is effective and operative in detection of the
      metallic, organic and mixed materials with acceptable accuracy.

PMID- 22635177
TI  - Finite detector based projection model for high spatial resolution.
AB  - For finite detector and focal spot sizes, here we propose a projection model for
      high spatial resolution. First, for a given x-ray source point, a projection
      datum is modeled as an area integral over a narrow fan-beam connecting the
      detector elemental borders and the x-ray source point. Then, the final projection
      value is expressed as the integral obtained in the first step over the whole
      focal spot support. An ordered-subset simultaneous algebraic reconstruction
      technique (OS-SART) is developed using the proposed projection model. In the
      numerical simulation, our method produces improved spatial resolution and
      suppresses high-frequency artifacts.

PMID- 22635178
TI  - SLATE: virtualizing multiscale CT training.
AB  - Training on micro- and nano- computed tomography (CT) scanners has been
      traditionally conducted via extensive practice on the instrument. This entails
      presence of an instructor to guide through the training procedure, until
      reasonable experience is attained. Modern tomographic instruments being expensive
      to maintain, the operational costs escalates with increasing number of training
      conducted. In a pioneering approach, the technical know-how to operate such
      equipment has been partly imparted via virtual reality environment running on the
      Second Life grid. The experimentation has indicated a reduction of the total
      training time. The authors hope that in the long run, such techniques will aid in
      significant reduction of instruction time and costs associated with training.

PMID- 22635179
TI  - In vivo photoacoustic imaging of model of port wine stains.
AB  - Port wine stains are categorized as a benign capillary vascular malformation,
      which is hard to cure. In this paper, a photoacoustic microscopy system, which
      integrated a two-dimensional scanning galvanometer, an objective lens and a
      focused ultrasound transducer, was designed for noninvasive imaging of blood
      vessels of port wine stains model in vivo. Cock comb was chosen as the port wine
      stains model in the experiment. The blood vessels in x-y plane and x-z plane were
      imaged clearly. Experimental results demonstrate that photoacoustic microscopy
      can image the blood vessels of port wine stains model in vivo with high contrast
      and high resolution. It has the potential for clinical applications in detecting
      the blood vessels in port wine stains skin.

PMID- 22635180
TI  - Wiser investment for a healthier future.

PMID- 22635181
TI  - Public health: a best buy for America.
AB  - Public health has considerable capacity to reduce the drag of health spending on
      our nation by preventing the leading causes of disease, death, and disability
      with cost-efficient, population-based interventions and innovative, boundary
      spanning approaches that link clinical care and community prevention. Public
      health is uniquely able to identify the burdens of disease and analyze the best
      strategies for addressing them. A 3-pronged strategy can help assure the value
      needed from our public health investments. First, we must center our efforts on
      prevention. Second, we must optimize our public health investments to achieve the
      greatest value for our investment. Third, public health must collaborate with
      traditional and new partners on initiatives and in funding. How we finance public
      health is critical to maximizing public health's benefits and requires thoughtful
      analysis of how federal funding affects state and local health agencies'
      programming and how allocation drives choices and design, among other topics, as
      discussed in this special issue of the journal.

PMID- 22635182
TI  - The increasing importance of public health funding research.

PMID- 22635183
TI  - Measuring progress in public health finance.

PMID- 22635184
TI  - Funding formulas for public health allocations:  federal and state strategies.
AB  - Public health funding formulas have received less scrutiny than those used in
      other government sectors, particularly health services and public health
      insurance. We surveyed states about their use of funding formulas for specific
      public health activities; sources of funding; formula attributes; formula
      development; and assessments of political and policy considerations. Results show
      that the use of funding formulas is positively correlated with the number of
      local health departments and with the percentage of public health funding
      provided by the federal government. States use a variety of allocative strategies
      but most commonly employ a "base-plus" distribution. Resulting distributions are
      more disproportionate than per capita or per-person-in-poverty allotments, an
      effect that increases as the proportion of total funding dedicated to equal
      minimum allotments increases.

PMID- 22635185
TI  - How federalism shapes public health financing, policy, and program options.
AB  - In the United States, fiscal and functional federalism strongly shape public
      health policy and programs. Federalism has implications for public health
      practice: it molds financing and disbursement options, including funding
      formulas, which affect allocations and program goals, and shapes how funding
      decisions are operationalized in a political context. This article explores how
      American federalism, both fiscal and functional, structures public health
      funding, policy, and program options, investigating the effects of
      intergovernmental transfers on public health finance and programs.

PMID- 22635186
TI  - Resource and cost adjustment in the design of allocation funding formulas in
      public health programs.
AB  - CONTEXT: Multiple federal public health programs use funding formulas to allocate
      funds to states. OBJECTIVE: To characterize the effects of adjusting formula
      based allocations for differences among states in the cost of implementing
      programs, the potential for generating in-state resources, and income
      disparities, which might be associated with disease risk. SETTING: Fifty US
      states and the District of Columbia. INTERVENTION: Formula-based funding
      allocations to states for 4 representative federal public health programs were
      adjusted using indicators of cost (average salaries), potential within-state
      revenues (per-capita income, the Federal Medical Assistance Percentage, per
      capita aggregate home values), and income disparities (Theil index). MAIN
      OUTCOME: Percentage of allocation shifted by adjustment, the number of states and
      the percentage of US population living in states with a more than 20% increase or
      decrease in funding, maximum percentage increase or decrease in funding. RESULTS:
      Each adjustor had a comparable impact on allocations across the 4 program
      allocations examined. Approximately 2% to 8% of total allocations were shifted,
      with adjustments for variations in income disparity and housing values having the
      least and greatest effects, respectively. The salary cost and per-capita income
      adjustors were inversely correlated and had offsetting effects on allocations.
      With the exception of the housing values adjustment, fewer than 10 states had
      more than 20% increases or decreases in allocations, and less than 10% of the US
      population lived in such states. CONCLUSIONS: Selection of adjustors for formula
      based funding allocations should consider the impacts of different adjustments,
      correlations between adjustors and other data elements in funding formulas, and
      the relationship of formula inputs to program objectives.

PMID- 22635187
TI  - Reference allocations and use of a disparity measure to inform the design of
      allocation funding formulas in public health programs.
AB  - Funding formulas are commonly used by federal agencies to allocate program funds
      to states. As one approach to evaluating differences in allocations resulting
      from alternative formula calculations, we propose the use of a measure derived
      from the Gini index to summarize differences in allocations relative to 2
      referent allocations: one based on equal per-capita funding across states and
      another based on equal funding per person living in poverty, which we define as
      the "proportionality of allocation" (PA). These referents reflect underlying
      values that often shape formula-based allocations for public health programs. The
      size of state populations serves as a general proxy for the amount of funding
      needed to support programs across states. While the size of state populations
      living in poverty is correlated with overall population size, allocations based
      on states' shares of the national population living in poverty reflect variations
      in funding need shaped by the association between poverty and multiple adverse
      health outcomes. The PA measure is a summary of the degree of dispersion in state
      specific allocations relative to the referent allocations and provides a quick
      assessment of the impact of selecting alternative funding formula designs. We
      illustrate the PA values by adjusting a sample allocation, using various measures
      of the salary costs and in-state wealth, which might modulate states' needs for
      federal funding.

PMID- 22635188
TI  - Assessing the level of public health partner spending using the funding formula
      analysis tool.
AB  - Public health services are delivered through a variety of organizations.
      Traditional accounting of public health expenditures typically captures only
      spending by government agencies. New Hampshire collected information from public
      health partners, such as community centers that host smoking cessation classes or
      health education done by Girls, Inc. This study compares the new data to spending
      by government agencies, focusing on breakdowns by fund source and service
      categories. Expanded funds secured by these partners account for a 42% of all
      local public health spending, and they spent 4 times more than government
      agencies on promoting healthy behavior. The funding formula analysis tool
      revealed that these partners spent in ways that would be politically difficult to
      achieve. In an era of declining budgets, an understanding of public health's
      partners is increasingly vital.

PMID- 22635189
TI  - Assessing the validity of self-reported community benefit expenditures: evidence
      from not-for-profit hospitals in California.
AB  - CONTEXT: In its revised Form 990 Schedule H, the Internal Revenue Service
      requires not-for-profit hospitals to provide detailed financial information on
      their community benefits, yet no standardized reporting guidelines exist for how
      these activities should be quantified. As a result, little is known currently
      about whether a hospital's self-reported community benefit expenditures provide
      an accurate picture of its commitment to serving the community. OBJECTIVE: To
      assess the validity of hospitals' self-reported community benefit expenditures.
      DATA AND METHODS: Data for this study came from California hospitals. Self
      reported community benefit expenditures were derived from hospitals' annual
      community benefit reports for the year 2009. Bivariate correlation analysis was
      used to compare self-reported expenditures to a set of indicators of hospitals'
      charitable activity. Of the 218 private, not-for-profit California hospitals that
      were required to submit community benefit reports for 2009, 91 (42%) provided
      sufficient information for our analysis. RESULTS: California hospitals' self
      reported community benefit expenditures were strongly correlated with indicators
      of charitable activity. Hospitals that reported higher community benefit
      expenditures engaged in more charitable activities than hospitals that reported
      lower levels of community benefit spending. CONCLUSION: Expenditure information
      from California hospitals' community benefit reports was found to be a valid
      indicator of charitable activity. Self-reported community benefit spending may
      thus provide a fairly accurate picture of a hospital's commitment to serving its
      community, despite the lack of standardized reporting guidelines.

PMID- 22635190
TI  - Public health spending in 2008: on the challenge of integrating PHSSR data sets
      and the need for harmonization.
AB  - In recent years, state and local public health department budgets have been cut,
      sometimes drastically. However, there is no systematic tracking of governmental
      public health spending that would allow researchers to assess these cuts in
      comparison with governmental public health spending as a whole. Furthermore,
      attempts to quantify the impact of public health spending are limited by the lack
      of good data on public health spending on state and local public health services
      combined. The objective of this article is to integrate self-reported state and
      local health department (LHD) survey data from 2 major national organizations to
      create state-level estimates of governmental public health spending. To create
      integrated estimates, we selected 1388 LHDs and 46 states that had reported
      requisite financial information. To account for the nonrespondent LHDs, estimates
      of the spending were developed by using appropriate statistical weights. Finally,
      funds from federal pass-through and state sources were estimated for LHDs and
      subtracted from the total spending by the state health agency to avoid counting
      these dollars in both state and local figures. On average, states spend $106 per
      capita on traditional public health at the state and local level, with an average
      of 42% of spending occurring at the local level. Considerable variation exists in
      state and local public health funding. The results of this analysis show a
      relatively low level of public health funding compared with state Medicaid
      spending and health care more broadly.

PMID- 22635191
TI  - Anatomy of a public health agency turnaround: the case of the general health
      district in Mahoning County.
AB  - A turnaround describes an organization's ability to recover from successive
      periods of decline. Current and projected declines in US economic conditions
      continue to place local public health departments at risk of fiscal exigency.
      This examination focused on turnaround methodologies used by a local public
      health department to reverse successive periods of operational and financial
      declines. Illustrations are provided on the value added by implementing financial
      ratio and trend analysis in addition to using evidence-based private sector
      turnaround strategies of retrenchment, repositioning, and reorganization.
      Evidence has shown how the financial analysis and strategies aided in identifying
      operational weakness and set in motion corrective measures. The Public Health
      Uniform Data System is introduced along with a list of standards offered for
      mainstreaming these and other routine stewardship practices to diagnose, predict,
      and prevent agency declines.

PMID- 22635192
TI  - Challenging times for the governmental public health enterprise.

PMID- 22635194
TI  - Using the internet to trace contacts of a fatal meningococcemia case-New York
      City, 2010.
AB  - In August 2010, the New York City Department of Health and Mental Hygiene (DOHMH)
      conducted an investigation to identify and provide antibiotic prophylaxis to
      close contacts of a patient who had died of invasive meningococcal disease.
      Traditional contact tracing, which relies on interviews with the patient's close
      associates, identified 3 persons meeting prophylaxis criteria. In addition, DOHMH
      learned of an Internet site used by the patient to arrange anonymous sexual
      encounters. By working with the Internet site administrator through a liaison,
      DOHMH sent notification to 15 additional persons potentially at risk for
      meningococcal disease; of those, at least 1 met prophylaxis criteria. The
      Internet has been used previously for partner notification by sexually
      transmitted disease control programs. This case report illustrates how the
      Internet can aid contact investigations for other communicable diseases,
      especially when identifying potential contacts is urgent, patients have died, or
      contacts are unknown to the patient's associates.

PMID- 22635193
TI  - Use of tuberculosis genotyping for postoutbreak monitoring.
AB  - CONTEXT: Review of routinely collected tuberculosis genotyping results following
      a known outbreak is a potential mechanism to examine the effectiveness of
      outbreak control measures. OBJECTIVE: To assess differences in characteristics
      between outbreak and postoutbreak tuberculosis cases. DESIGN: Retrospective.
      SETTING: United States. PARTICIPANTS: All tuberculosis cases identified as a
      result of >5-person outbreaks investigated by the Centers for Disease Control and
      Prevention during 2003 to 2007 (original outbreak cases), and subsequent culture
      positive tuberculosis cases with matching Mycobacterium tuberculosis genotypes
      reported in the same county during 2004 to 2008 (postoutbreak cases). MAIN
      OUTCOME MEASURE: Proportion of demographic, social, and clinical characteristics
      of tuberculosis outbreak cases compared to postoutbreak cases. SECONDARY:
      Proportion of demographic, social, and clinical characteristics of
      epidemiologically linked versus nonlinked cases. RESULTS: Six outbreaks with 111
      outbreak cases and 110 postoutbreak cases were identified. Differences between
      outbreak and postoutbreak cases were gender (69% vs 85% male; P < .01), birth
      origin (3% vs 11% foreign-born; P = .02), disease severity (48% vs 62% sputum
      smear-positive; P = .04), homelessness (38% vs 51%; P = .05), and injection drug
      use (4% vs 11%; P = .04). For 5 of the 6 outbreaks, the status of epidemiologic
      relationships among postoutbreak cases was available (n = 89). The postoutbreak
      cases with a known epidemiologic link to the original outbreak were in younger
      persons (aged 39 vs 47 years; P < .01), and a larger proportion reported
      injection drug use (18% vs 4%; P = .04) or noninjection drug use (44% vs 18%; P <
      .01) than those without a reported link. CONCLUSIONS: Health jurisdictions can
      utilize genotyping data to monitor and define the characteristics of postoutbreak
      cases related to the original outbreak.

PMID- 22635195
TI  - Igniting interest in prevention:  using firefighter focus groups to inform
      implementation and enhancement of an urban canvassing program.
AB  - CONTEXT: Smoke alarm canvassing is recognized as an empirically based, effective
      intervention for increasing access to and the presence of smoke alarms in homes.
      OBJECTIVES: We sought to inform the implementation of an intervention designed to
      enhance an existing fire department smoke alarm canvassing program through an
      empirically grounded, participatory process. DESIGN: We conducted a series of
      focus groups with fire union leaders and firefighters involved with the
      canvassing program in 1 US city, shared the results with the participants, and
      presented the resulting recommendations to fire department leadership. SETTING:
      This research occurred in Baltimore, Maryland. PARTICIPANTS: Focus group
      participants included firefighters who participate in the Fire Department's smoke
      alarm canvassing program and representatives from the local firefighters' union.
      MAIN OUTCOME MEASURES: The focus groups sought to capture firefighters'
      experiences with and opinions about the canvassing program and how to improve it
      as well as challenges to canvassing work. RESULTS: We conducted 10 focus groups
      with 65 participants. Firefighters' perspectives on the canvassing program and
      their recommendations for improving it were expressed through 3 categories of
      themes concerning program management, canvassing challenges, and attitudes about
      the program and the community. We also discuss the process of presenting these
      findings and recommendations to the participants and the fire department
      leadership, and describe how implementation of some of the recommendations has
      progressed. CONCLUSIONS: Both the process and outcomes of this formative work
      inform how to develop and implement community-based public health interventions
      in real-world settings through academic-community partnerships. The findings also
      have implications for how canvassing programs are being implemented.

PMID- 22635196
TI  - Budgetary decision making during times of scarcity.

PMID- 22635197
TI  - NACCHO monitors the financial health of local health departments: new tools make
      financial data more accessible to public health practitioners.

PMID- 22635198
TI  - The health law partnership:  adding a lawyer to the health care team reduces
      system costs and improves provider satisfaction.
AB  - Addressing the legal issues of patients of low socioeconomic status can be useful
      in increasing organizational reimbursements, reducing costs and improving access
      to care. Medical-legal partnership is an addition to the health care
      armamentarium that directly addresses this goal. A medical-legal partnership is
      an interdisciplinary collaboration between a medical entity such as a hospital or
      clinic and a legal entity such as a law school or legal aid society that
      addresses barriers to access to care and limitations to well-being experienced by
      patients of low socioeconomic status. The Health Law Partnership is one such
      medical legal partnership that provides a holistic, interdisciplinary approach to
      health care. An evaluation of the legal and educational services provided by
      Health Law Partnership showed that Health Law Partnership secured otherwise
      unreimbursed Medicaid payments for services over a 4-year period from 2006 to
      2010, increased physician satisfaction, and saved hospital employers
      approximately $10 000 in continuing education costs annually.

PMID- 22635199
TI  - The public health disaster trust scale:  validation of a brief measure.
AB  - CONTEXT: Trust contributes to community resilience by the critical influence it
      has on the community's responses to public health recommendations before, during,
      and after disasters. However, trust in public health is a multifactorial concept
      that has rarely been defined and measured empirically in public health
      jurisdictional risk assessment surveys. Measuring trust helps public health
      departments identify and ameliorate a threat to effective risk communications and
      increase resilience. Such a measure should be brief to be incorporated into
      assessments conducted by public health departments. OBJECTIVE: We report on a
      brief scale of public health disaster-related trust, its psychometric properties,
      and its validity. DESIGN: On the basis of a literature review, our conceptual
      model of public health disaster-related trust and previously conducted focus
      groups, we postulated that public health disaster-related trust includes 4 major
      domains: competency, honesty, fairness, and confidentiality. SETTING: A random
      digit-dialed telephone survey of the Los Angeles county population, conducted in
      2004-2005 in 6 languages. PARTICIPANTS: Two thousand five hundred eighty-eight
      adults aged 18 years and older including oversamples of African Americans and
      Asian Americans. MAIN OUTCOME MEASURES: Trust was measured by 4 items scored on a
      4-point Likert scale. A summary score from 4 to 16 was constructed. RESULTS:
      Scores ranged from 4 to 16 and were normally distributed with a mean of 8.5 (SD
      2.7). Cronbach alpha = 0.79. As hypothesized, scores were lower among
      racial/ethnic minority populations than whites. Also, trust was associated with
      lower likelihood of following public health recommendations in a hypothetical
      disaster and lower likelihood of household disaster preparedness. CONCLUSIONS:
      The Public Health Disaster Trust scale may facilitate identifying communities
      where trust is low and prioritizing them for inclusion in community partnership
      building efforts under Function 2 of the Centers for Disease Control and
      Prevention's Public Health Preparedness Capability 1. The scale is brief,
      reliable, and validated in multiple ethnic populations and languages.

PMID- 22635200
TI  - Screening for Mycobacterium tuberculosis using an interferon-gamma release assay.
AB  - CONTEXT: The Centers for Disease Control and Prevention recommend analyzing
      characteristics of populations screened for Mycobacterium tuberculosis infection
      using interferon-gamma release assays (IGRAs). OBJECTIVE: We characterized
      requests for IGRA analyses submitted to the first laboratory in Washington State
      that began to offer IGRAs as a tuberculosis screening test. In addition, we
      chronicled the process by which this program was launched. DESIGN: Through a
      retrospective record review we recorded the IGRA results, source of the request,
      and reason(s) for each request along with demographic information, risk factors,
      and prior exposure for each subject. Through dissemination and quality control
      measures, IGRA analyses began within the health district but quickly spread
      throughout the state and the West. SETTING AND PARTICIPANTS: A regional health
      district clinical laboratory in the Pacific Northwest received 4422 IGRA requests
      for 4218 unique subjects from January 2, 2008, through June 5, 2009. RESULTS:
      Most (96%) requests originated from public health clinics or centers, hospitals,
      private laboratories or practitioners, and Indian Health Centers. Community and
      migrant health centers had the highest rates of positive IGRA results (28%, Phic
      = 0.159, P = .000). About one-half of all requests were for employment or high
      risk surveillance. Persons with a positive IGRA had a larger TST induration (M =
      16.66 mm, 95% CI: 15.18-18.14) than those with a negative IGRA (M = 13.53 mm, 95%
      CI: 12.92-14.15) but did not differ for those with an indeterminate IGRA (M =
      13.29 mm, 95% CI: 5.95-20.62). CONCLUSIONS: Public and private agencies use IGRAs
      for surveillance of persons employed, routinely screened, at high risk, or
      foreign-born. The TST induration varies widely for persons with an indeterminate
      IGRA. The process for implementing IGRA analyses serves as a model for other
      programs seeking to conduct similar reviews of test use and results.

PMID- 22635201
TI  - Use, location, and timeliness of clinical microbiology testing in Georgia for
      select infectious diseases.
AB  - OBJECTIVE: Although clinical microbiology testing facilitates both public health
      surveillance of infectious diseases and patient care, research on testing
      patterns is scant. We surveyed hospital laboratories in Georgia to assess their
      diagnostic testing practices. METHODS: Using e-mail, all directors of hospital
      laboratories in Georgia were invited to participate. The survey focused on timing
      and location of diagnostic testing in 2006 for 6 reportable diseases: giardiasis,
      legionellosis, meningococcal disease, pertussis, Rocky Mountain spotted fever,
      and West Nile virus disease. RESULTS: Of 141 laboratories, 62 (44%) responded to
      the survey. Hospitals varied widely in their use of diagnostic testing in 2006,
      with 95.1% testing for meningococcal disease, but only 66.1% and 63.3% testing
      for legionellosis and West Nile virus disease, respectively. Most laboratories
      (91%) performed gram stain/culture to diagnose meningococcal disease in-house and
      23% performed ova and parasite panels for giardiasis were conducted in-house.
      Fewer than 11% of laboratories performed in-house testing for the remaining
      diseases. Laboratories affiliated with small hospitals (<=100 beds) were more
      likely to send specimens for outside testing compared with laboratories
      associated with large hospitals (>250 beds). Median turnaround time for ova and
      parasite panel testing for giardiasis was significantly shorter for in-house
      testing (1.0 days) than within-system (2.25 days) or outside laboratory (3.0
      days) testing (P = .0003). No laboratories reported in-house testing for
      meningococcal disease, pertussis, or Rocky Mountain spotted fever using
      polymerase chain reaction. CONCLUSION: Many hospitals did not order diagnostic
      tests for important infectious diseases during 2006, even for relatively common
      diseases. In addition, hospital laboratories were unlikely to perform diagnostic
      testing in-house; sending specimens to an outside laboratory may result in
      substantial delays in receiving results. These unsettling findings have adverse
      implications for both patient care and public health surveillance; they indicate
      an immediate need to study nationally the use and timeliness of clinical
      microbiologic testing.

PMID- 22635202
TI  - Highly regioirregular polypropylene from asymmetric group 4
      anilide(pyridine)phenoxide complexes.
AB  - Group 4 complexes containing an anilide(pyridine)phenoxide ligand and activated
      with methylaluminoxane (MAO) catalyze the formation of highly regioirregular
      polypropylene.

PMID- 22635203
TI  - Traceless chemical ligations from O-acyl serine sites.
AB  - Chemical ligation via O- to N-acyl transfer of O-acylated serine containing
      peptides affords serine containing native peptides via 8- and 11-membered cyclic
      transition states opening the door to a wide variety of potential applications to
      peptide elaboration. The feasibility of these traceless chemical ligations is
      feasible as supported by computation.

PMID- 22635206
TI  - European Forum On Antiphospholipid Antibodies: brief history report and
      governance document.
AB  - The European Forum on Antiphospholipid Antibodies was conceived as a
      multidisciplinary network of different specialists working in the fields of
      internal medicine, haematology, rheumatology, obstetrics and gynaecology,
      neurology, paediatrics, cardiology and immunology, among others, that share a
      common interest in these antibodies and antiphospholipid syndrome (APS). Centres
      with very good clinical practice in APS and with large cohorts of patients could
      join other centres with better research experience, thus allowing the study of
      basic patho-mechanisms in large series of patients. In addition, the specialists
      would be able to compare their cohorts of patients, which, being as they are
      recruited in very different fields of medicine, could enlighten the different
      aspects of APS. Finally, continuous comparison of patients' data suggested that
      even the laboratory diagnostic procedures needed collaborative work in order to
      make reproducible results, at least of the classical tests--lupus anticoagulant
      (LA), anticardiolipin antibodies (aCLas) and anti beta(2)-glycoprotein I
      antibodies (anti-beta(2)GPIs)--and of the consequent clinical diagnosis in
      different centres. In this way, the wide exchange of information could also
      favour the introduction and evaluation of new tests.

PMID- 22635205
TI  - APS ACTION--AntiPhospholipid Syndrome Alliance For Clinical Trials and
      InternatiOnal Networking.
AB  - AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal
      Networking (APS ACTION) is the first-ever international research network that has
      been created specifically to design and conduct well-designed, large-scale, multi
      center clinical trials in persistently antiphospholipid antibody (aPL)-positive
      patients. The founding principle of the APS ACTION is that it is an
      internationally collaborative effort, open to qualified investigators across the
      globe who are committed to furthering our understanding of APS and its
      management. Due to the hard work and collaborative spirit of APS ACTION members,
      in early 2012, APS ACTION launched two important collaborative international
      projects: 1) a randomized controlled trial of hydroxychloroquine in the primary
      thrombosis prevention of persistently aPL-positive but thrombosis-free patients
      without other systemic autoimmune diseases; and 2) a web-based registry of aPL
      positive patients with or without systemic autoimmune diseases, which will also
      include annual blood collection for aPL-testing and future basic science studies.
      In the end, we hope to find better treatments for antiphospholipid syndrome,
      which is a leading cause of thrombosis, pregnancy morbidity and other life
      altering consequences, and to heighten awareness about this life-threatening,
      autoimmune condition.

PMID- 22635207
TI  - Pathophysiology of thrombotic APS: where do we stand?
AB  - The antiphospholipid syndrome (APS) is diagnosed when patients with thrombotic
      complications or foetal losses have elevated levels of antiphospholipid
      antibodies in their plasmas. The term APS is confusing, because the pathogenic
      auto-antibodies are not directed against phospholipids but towards a plasma
      protein, beta(2)-glycoprotein I. For many years the reason why auto-antibodies
      against beta(2)-glycoprotein I were pro-thrombotic was unclear, because man and
      mice deficient in beta(2)-glycoprotein I do not express a clear phenotype. Animal
      models in which passive transfer of patient antibodies into mice resulted in an
      increased thrombotic response have provided novel insights in the importance of
      this protein in the pathology of APS.

PMID- 22635208
TI  - Obstetric and vascular APS: same autoantibodies but different diseases?
AB  - Beta2 glycoprotein I (beta2GPI)-dependent antiphospholipid antibodies (aPLs) are
      the main pathogenic autoantibody population and at the same time the laboratory
      diagnostic tool for the antiphospholipid syndrome (APS). These antibodies are
      responsible for both the vascular and the obstetric manifestations of the
      syndrome but the pathogenic mechanisms behind these manifestations are not the
      same. For example, thrombotic events do not appear to play a major role in APS
      miscarriages and a direct reactivity of beta2GPI-dependent aPLs on decidual and
      trophoblast cells was reported. A local expression of beta2GPI on these tissues
      was reported both in physiological conditions and in APS women, thus explaining
      the local tropism of the autoantibodies. The two hit hypothesis was suggested to
      explain why the vascular manifestations of APS may occur only occasionally in
      spite of the persistent presence of aPLs. This is not apparently the case for the
      obstetric variant of the syndrome, making the difference even more striking. A
      different pathogenesis may also provide the rationale for the well-known fact
      that the vascular and the obstetric manifestations may occur independently
      although in a minority of cases.

PMID- 22635209
TI  - When APS (Hughes syndrome) met the autoimmune/inflammatory syndrome induced by
      adjuvants (ASIA).
AB  - Vaccination of healthy individuals is the most effective approach to protect the
      public from infections and prevent the spread of many infectious diseases all
      over the globe. Licensed vaccines are mostly safe, but in rare cases they may be
      associated with humoral response to self-antigens due to molecular mimicry,
      epitope spread, bystander activation or polyclonal triggering. Moreover, the
      clinical picture of autoimmune conditions following post-vaccination is rarer.
      Nevertheless, anecdotal case reports on the flare of autoimmune response with
      clinical manifestations were reported. Herein, we discuss this topic in relation
      to post-vaccination-induced antiphospholipid antibodies following tetanus toxoid
      vaccine, HBV and influenza associated in rare cases with antiphospholipid
      syndrome clinical manifestations. We will discuss the possible mechanisms which
      pertain to ASIA (Shoenfeld syndrome).

PMID- 22635210
TI  - Standardization of lupus anticoagulant. The Lupus Anticoagulant Sensitivity Index
      (LASI).
AB  - Results for lupus anticoagulant (LA) are expressed as ratio of patient-to-normal
      clotting times (LA-ratio) according to the equation LA-ratio = (Patient(Clotting
      time)/Normal(Clotting time)). However, numerical results vary according to the
      method used for testing, thus making difficult the between-method and between
      laboratory comparison of results. The hypothesis that the standardization model
      currently employed for the international normalized ratio for patients on
      warfarin is valid also for LA standardization has been taken into consideration.
      The model calls for the determination of a LA-sensitivity index (LASI) for each
      commercial method for LA detection against a common standard method. The LASI is
      then used to convert the LA-ratio into a scale called standardized LA-ratio (SLA
      ratio) according to the equation SLA-ratio = (LA-ratio)(LASI). The model proved
      effective in minimizing the between-method variability of results for LA
      detection. If implemented it could be a valuable tool to improve the
      comparability of results obtained in different laboratories, to quantify the LA
      potency and thus pave the way to the organization of collaborative clinical
      trials aimed at assessing whether the potency of LA is a risk factor for clinical
      events.

PMID- 22635211
TI  - Standardization of antiphospholipid antibody assays. Where do we stand?
AB  - The laboratory criteria (lupus anticoagulants (LA), and/or anti-cardiolipin (aCL)
      antibodies and/or anti-beta2-glycoprotein I antibodies (abeta2GPI)) that define
      patients with antiphospholipid syndrome (APS) were set in the Sapporo and Sydney
      criteria published in 1999 and 2006, respectively, and led to a substantial
      improvement in the recognition of APS. In addition, guidelines for LA detection
      were published by the Scientific Standardisation Subcommittee (SSC) of the
      International Society of Thrombosis and Haemostasis (ISTH) in 2009. However, a
      number of questions on this respect remain unresolved. Recommendations for the
      aCL and abeta2GPI assays intended to ameliorate the performance of these solid
      phase assays. Despite efforts over the years, standardization has not been
      reached. This review will focus on methodological issues of the three
      antiphospholipid antibody (aPL) subtypes that are the subject of debate. The use
      of an international standard for aPL detection might help solve many of the
      problems caused by a lack of standardization of these assays.

PMID- 22635212
TI  - In ECAT veritas?
AB  - The laboratory criteria of the antiphospholipid syndrome include one coagulation
      assay (lupus anticoagulant [LA]) and two solid phase assays (anticardiolipin
      [aCL] and anti-beta(2)glycoprotein I antibodies [abeta(2)GPI]). External quality
      control (EQC) surveys show that negative and clearly positive LA samples are
      classified correctly by about 95% of laboratories. For 'weak' LA there is a wide
      variability in samples' classification. Furthermore, when a weak LA sample is
      used in two different EQC surveys more than 50% of laboratories classify it
      differently. In some surveys weak LA samples were found to be positive for aCL
      and for abeta(2)GPI by a majority of laboratories; the main reason for
      laboratories which classified these samples as LA negative was a negative result
      in the mixing test. It is likely that, depending on the sensitivity of the assay,
      a weak LA cannot be detected anymore after 1:1 dilution of the sample with normal
      plasma. Therefore, we recommend the use of integrated assays, such as
      screen/confirm ratios, for the detection of weak LA samples.

PMID- 22635213
TI  - Definition and significance of high positivity aCL ELISA.
AB  - We conducted a prospective study of anticardiolipin antibody (aCL) testing,
      performed in our university hospital. Among 6321 consecutive patients tested for
      both IgG and IgM aCL, 91 patients with medium or high positivity (>99th
      percentile) had a subsequent confirmatory test. Among them, 53 had a persistent
      positivity at 12 weeks. In this real world setting, patients with transient
      positivity had lower values than patients with persistent positivity.

PMID- 22635214
TI  - The contribution of antiphosphatidylethanolamine antibodies in the diagnosis of
      the antiphospholipid syndrome.
AB  - The diagnosis of seronegative antiphospholipid syndrome (APS) has been proposed
      for patients with well-defined clinical APS but persistently negative for the
      routinely tested antiphospholipid antibodies (aPLs): antibodies to cardiolipin
      (aCL) and to beta(2) glycoprotein I (abeta(2)GPI) and lupus anticoagulant (LA).
      Antibodies directed to phosphatidylethanolamine (aPE) have been described as the
      sole aPLs in some patients with clinical manifestations of APS. Here, we briefly
      summarize the available data on the clinical associations of aPEs and propose
      their investigation in patients with a clinical profile highly suggestive of
      seronegative APS.

PMID- 22635215
TI  - Antibodies to prothrombin.
AB  - Research on antiphospholipid antibodies (aPL) and the thrombotic manifestations
      associated with these antibodies has grown since the description of
      anticardiolipin antibodies (aCL) by Harris and colleagues in the early 1980s.
      Antiprothrombin (aPT) antibodies are commonly detected by ELISA, using irradiated
      plates (aPT) or prothrombin in complex with phosphatidylserine (aPS/PT). Although
      aPT and/or aPS/PT are associated with antiphospholipid syndrome (APS) -related
      clinical features and these antibodies correlate with each other, aPT and aPS/PT
      belong to different populations of autoantibodies even though they can both be
      present in the same patient. Early studies suggested that these antibodies might
      be the antigenic target of lupus anticoagulant (LA) and their correlation and
      clinical significance is being investigated.

PMID- 22635216
TI  - Interpretation of laboratory data and need for reference laboratories.
AB  - A single positive laboratory test among those exploring the presence of
      antiphospholipid antibodies is not associated with thromboembolic events and does
      not identify patients with antiphospholipid syndrome. On the other hand, more
      than one laboratory test positive, and in particular all three tests positive, is
      strongly associated to thromboembolic events and identifies high risk patients.
      Triple positivity is in fact related to the presence of a specific anti-beta2
      glycoprotein I (anti-Domain I) antibody, also able to prolong coagulation tests.
      Monoclonal antibodies against Domain I with Lupus Anticoagulant activity might be
      candidate material for standardization of antiphospholipid assays. Much work
      remains to be done in this field.

PMID- 22635217
TI  - Secondary prevention in thrombotic antiphospholipid syndrome.
AB  - Secondary prevention of venous thromboembolism in antiphospholipid syndrome (APS)
      is usually made using vitamin K antagonists (VKAs) to maintain an international
      normalized ratio (INR) between 2.0 and 3.0. The optimal intensity of
      anticoagulation was determined in two prospective randomized controlled trials,
      both excluding the benefit of more intense anticoagulation. The same regimen is
      also recommended in patients with APS and arterial thromboembolism as aspirin
      does not appear to protect against recurrences. The duration of treatment is
      usually indefinite because of a substantial risk of recurrence.

PMID- 22635218
TI  - Vitamin D and antiphospholipid syndrome.
AB  - Vitamin D (vitD) has been shown to have multiple immunomodulatory properties.
      Hypovitaminosis D has been described in many systemic autoimmune diseases.
      Antiphospholipid syndrome (APS), an autoimmune disease characterized by immune
      mediated thrombosis and pregnancy loss, is a peculiar model for studying vitD,
      since these patients do not usually have a full-blown autoimmune disease, nor do
      they have particular restrictions regarding sun exposure. We assessed 25-OH vitD
      levels in 115 APS and 128 normal healthy donors (NHD) with the LIAISON(r)
      chemiluminescent immunoassay by DiaSorin (Italy). Median values were lower in APS
      patients than in NHD, with the greatest difference occurring during summertime (p
      < 0.01), suggesting that APS patients may be somehow prevented from vitD
      generation upon sun exposure. In our cohort, APS patients may have been
      instructed to use sunscreens in the presence of positive antinuclear antibodies
      (ANA). Comparing patients with positive and negative ANA, we found comparable
      vitD levels during the summer. By subdividing APS patients according to clinical
      features, thrombotic APS patients showed significantly lower levels than did pure
      obstetric APS patients (p < 0.01). In conclusion, our study confirms previous
      reports of hypovitaminosis D in APS patients, making them more similar to
      patients with other systemic autoimmune diseases than NHD. Hypovitaminosis D may
      be part of the mosaic of factors that determine autoimmunity, rather than a
      consequence of chronic disease and its treatment. The observation that patients
      with thrombotic APS, an aggressive phenotype, may be more deficient than those
      with exclusive obstetric manifestations fits well with the beneficial effects of
      vitD on thrombosis described both in vitro and in vivo. Therefore, there may be a
      rationale to assess the efficacy of vitD supplementation in APS patients.

PMID- 22635219
TI  - Risk-based secondary prevention of obstetric antiphospholipid syndrome.
AB  - Treatment of pregnant women with antiphospholipid syndrome (APS) should be set
      apart from that from thrombotic APS patients. Patients with a history of
      pregnancy morbidity but no vascular thrombosis are usually treated with a
      prophylactic dose of heparin plus low-dose aspirin; whereas, those with previous
      vascular thrombosis alone or associated with previous pregnancy morbidity, are
      commonly treated with a therapeutic dose of heparin generally combined with low
      dose aspirin. However, in about 20% of pregnant APS women these regimens fail. In
      this context, we conducted a case-control study on a large multicentre cohort of
      conventionally treated pregnancies to verify whether specific laboratory profiles
      and/or clinical characteristics are predictive of unsuccessful pregnancy outcome
      during conventional treatments. Multivariate analysis showed that pregnancy
      failure during conventional therapies was independently associated with a history
      of both thrombosis and pregnancy morbidity, the presence of systemic lupus
      erythematosus (SLE) or other systemic autoimmune diseases and triple
      antiphospholipid antibody positivity. With the aim to discover the most effective
      and safe treatments in high-risk pregnant APS women a large-scale multicentre
      study focusing on the effect of treatments on pregnancy outcome in women with APS
      and further risk factors for pregnancy failure has been designed.

PMID- 22635220
TI  - Repeated miscarriages in patients with antiphospholipid syndrome and subjected to
      in vitro fertilization: the importance of preimplantation genetic diagnosis.
AB  - The aim of this study was to investigate two patients with antiphospholipid
      syndrome (APS) who suffered from multiple repeated pregnancy losses of probably
      genetically impaired embryos. Sera from these patients contained high levels of
      IgG antibodies against cardiolipin, IgG and IgM phosphatidyl inositol, IgG
      phosphatidyl L-serine, and IgG against anti-annexin V. The conventional treatment
      of APS was ineffective. Preimplantation genetic diagnosis (PGD) showed
      chromosomally impaired embryos. The course of pregnancies and deliveries were
      monitored due to the close collaboration of in vitro fertilization and PGD in
      early embryos. After the selection of normal embryos using PGD, and the treatment
      of APS, both patients became pregnant and delivered healthy babies. Without such
      selection, both women would probably have miscarried their embryos again.

PMID- 22635221
TI  - Primary antithrombotic prevention in carriers of antiphospholipid antibodies
      without systemic autoimmune disorders.
AB  - Primary antithrombotic prevention with aspirin is not indicated in asymptomatic
      patients with confirmed antiphospholipid (aPL) positivity without systemic
      autoimmune disorders because: a) the estimated prevalence of thrombosis in
      unselected cases is about 1% patient-years (range 0-2.8); b) this level of
      thrombotic risk is equivalent to that of major bleeding associated with the use
      of aspirin and therefore the expected benefit does not outweigh the risk; c)
      these expectations have been confirmed by at least one randomized clinical trial,
      although with methodological limits. The management of modifiable thrombotic risk
      factors can be an alternative and safer strategy, considering that many vascular
      events occur in the presence of concomitant non-aPL triggering conditions.
      Whether primary prophylaxis with aspirin may be useful for some subsets of aPL
      patients at particularly high thrombotic risk, such as those with overt systemic
      autoimmune disorders or with special patterns of antibodies ('triple
      positivity'), remains to be established.

PMID- 22635222
TI  - Primary prevention in antiphospholipid antibody carriers.
AB  - The discovery of antiphospholipid antibodies (aPL) positivity in individuals who
      have never experienced thrombosis or pregnancy complications is not a rare event,
      and is one of the unresolved issues in the field of antiphospholipid syndrome
      (APS). This paper focuses on primary prophylaxis for thrombotic events in aPL
      carriers. In our view, patients with high risk aPL profiles and/or other
      cardiovascular risk factors, concomitant diagnosis of systemic lupus
      erythematosus (SLE) and patients with an history of obstetric APS (OAPS) should
      be offered thromboprophylaxis. Chronic thromboprophylaxis with low-dose aspirin
      and hydroxychloroquine in aPL positive SLE patients should be prescribed both to
      prevent thrombosis and to avoid early organ damage.

PMID- 22635223
TI  - CAPS Registry.
AB  - Patients with catastrophic antiphospholipid syndrome (APS) have in common: a)
      clinical evidence of multiple organ involvement developing over a very short
      period of time; b) histopathological evidence of multiple small vessel
      occlusions, and c) laboratory confirmation of the presence of antiphospholipid
      antibodies (aPL), usually in high titre. Although patients with catastrophic APS
      represent less than 1% of all patients with APS, they are usually in a life
      threatening situation. The rarity of this syndrome makes it extraordinarily
      difficult to study in any systematic way. In order to correlate all the published
      case reports as well as newly diagnosed cases from all over the world, an
      international registry of patients with catastrophic APS (CAPS Registry) was
      created in 2000 by the European Forum on aPL. Currently, it documents the
      clinical, laboratory and therapeutic data of more than 400 patients and can be
      consulted through Internet at www.med.ub.es/MIMMUN/FORUM/CAPS.HTM. The analysis
      of this registry has allowed the characterization of the clinical and laboratory
      features of the catastrophic APS as well as the establishment of preliminary
      criteria for its classification and guidelines for its management.

PMID- 22635224
TI  - Thrombin generation in antiphospholipid syndrome.
AB  - Our objective was to study acquired Activated Protein C (APC) resistance in
      patients with antiphospholipid antibodies (aPL) using a thrombin generation based
      assay. We compared patients with and without lupus (systemic lupus erythematosus,
      SLE). A parameter summarizing APC inhibition of thrombin generation with
      increasing APC concentrations (IC(50)-APC) was increased in all patient groups
      compared to controls: median values were 15.3 (interquartile range, IQR, 9.7 to
      34.0) in patients with primary antiphospholipid syndrome (APS), 27.3 (IQR 23.5 to
      43.5) in patients with SLE without APS, 64.1 (IQR 25.9 to 65.0) in patients with
      SLE/APS compared to 10.4 [IQR 8.5 to 15.8] in controls, respectively p = 0.003, p
      = 0.0001 and p = 0.0001. In conclusion, patients with SLE and primary APS
      displayed a hypercoagulable state characterized by APC resistance.

PMID- 22635225
TI  - Follow-up of babies born to mothers with antiphospholipid syndrome: preliminary
      data from the European neonatal registry.
AB  - In this review preliminary data on the follow-up of 141 babies born to mothers
      with antiphospholipid syndrome are reported. In spite of maternal treatment, the
      rate of both preterm delivery and low birth weight were 16 and 17%, respectively.
      At birth, no clinical evidence of perinatal thrombosis was observed. Placental
      transfer of antiphospholipid antibodies occurred in 20, 25 and 43% of cases for
      lupus anticoagulant, anticardiolipin and anti-beta2-glycoprotein I antibodies,
      respectively. At 24 months of follow-up, four children showed behaviour
      abnormalities suggesting the possible need for long-term neurological evaluation
      in this clinical setting.

PMID- 22635226
TI  - Avidity of anti-beta2-glycoprotein I antibodies in patients with antiphospholipid
      syndrome.
AB  - Antibodies against beta(2)-glycoprotein I (anti-beta(2)GPI) are one of the
      hallmarks of the antiphospholipid syndrome (APS). However, they are heterogenic
      regarding their epitope specificity, pathogenic mechanisms and their avidity. In
      the current study we present some outstanding issues about avidity of anti
      beta(2)GPI antibodies. Our results confirmed that high avidity anti-beta(2)GPI
      are associated with thrombosis and APS, while in low avidity anti-beta(2)GPI
      group non-APS (predominantly systemic lupus erythematosus) patients prevailed.

PMID- 22635227
TI  - The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): a
      preliminary first year report.
AB  - BACKGROUND: Obstetric morbidity (OM) is a common feature of antiphospholipid
      syndrome (OAPS). Women having OAPS-only and women with OM related to
      antiphospholipid antibodies (aPL) but not fulfilling APS classification criteria
      (OMAPS), may show similar patterns. AIM: The aim of this research was to collect
      records of OAPS and OMAPS cases in order to have valuable information about their
      clinical features, laboratory, treatment, pregnancy outcomes and long-term follow
      up. METHODS: EUROAPS/EUROMAPS is a registry in the frame of the European Forum on
      Antiphospholipid Antibody projects. Its own website has been available since June
      2010: www.euroaps.org. RESULTS: This registry comprises 211 women including 304
      pre-enrolment pregnancies, and 226 prospective cases, 194 of OAPS and 32 of
      OMAPS. OM was more frequent in OAPS than in OMAPS, independent of treatment. In
      the prospective cohort, standard aPL data was available in 202 cases and
      treatment data in all 226 cases. Good fetal outcomes were obtained when low dose
      aspirin plus low molecular weight heparin were administered. Prevalence of
      thrombotic events and/or cases evolving into full-blown systemic lupus
      erythematosus (SLE) was low. CONCLUSIONS: OAPS could be a different form of APS.
      OMAPS/OMAPS fetal outcomes were better when treated. The prevalence of thrombosis
      and progression to SLE were lower than in 'classical' APS.

PMID- 22635228
TI  - Antibodies against domain I of beta2-glycoprotein I: the one and only?
AB  - The antiphospholipid syndrome (APS) is diagnosed by the occurrence of thrombosis
      and/or specific pregnancy morbidity. However, the diagnosis of APS is not easy
      and is hampered by several problems including high prevalence of clinical
      symptoms and high variability between different assays resulting in a high false
      positive rate. Currently APS can be diagnosed for example by detecting anti-beta2
      glycoprotein I antibodies by ELISA. It has been reported that beta2-glycoprotein
      I (beta2GPI) changes its conformation from a native to an active form and thereby
      it opens up enabling antibodies to bind a specific epitope. We amongst others
      have shown that epitope glycine40-arginine43 of domain I of beta2GPI is
      predominantly responsible for binding thrombosis related antibodies. Antibodies
      with affinity towards other epitopes have not been associated with thrombosis.
      Despite these results the question remains whether these domain I antibodies are
      the only antibodies of importance for the detection of APS.

PMID- 22635229
TI  - The relationship between TORCH complex false positivity and obstetric outcome in
      patients with antiphospholipid syndrome.
AB  - OBJECTIVE: The presence of TORCH IgM positivity is not a specific indicator of
      primary infection; the assessment of IgG avidity index has been shown to be
      useful in identifying or excluding primary infection in pregnant women with no
      pre-gestational TORCH serology. TORCH is an acronym for Toxoplasmosis, Others
      (HBV, syphilis, Varicella-Zoster virus, Epstein Barr virus, Coxsackie virus and
      Parvovirus), Rubella, Cytomegalovirus (CMV) and Herpes Simplex. PATIENTS AND
      METHODS: Data from 54 pregnancies in women with antiphospholipid syndrome (APS)
      were assessed in comparison with data from 222 healthy pregnant women as
      controls. Each woman in both groups was systematically screened for TORCH IgG and
      IgM during pre-conceptional evaluation and/or at the beginning of pregnancy. The
      assessment of IgG avidity was also evaluated in order to identify primary
      infection or false positivity. RESULTS: A significant increase of CMV IgM false
      positivity in APS in comparison with controls was detected. A worse pregnancy
      outcome was observed among APS patients having CMV IgM false positivity in
      comparison with APS patients without false positivity; in particular a
      statistically significant lower neonatal birth weight and a lower neonatal birth
      weight percentile were observed. CONCLUSION: Our data suggest that the presence
      of CMV IgM false positivity could represent a novel prognostic factor for poor
      pregnancy outcome in APS patients.

PMID- 22635230
TI  - Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome.
AB  - OBJECTIVE: To investigate the predictive value of serum C3 and C4 complement
      component levels in relation to pregnancy outcome in patients with
      antiphospholipid syndrome (APS). MATERIALS AND METHODS: A prospective study of 47
      pregnancies associated with APS was performed. Pregnancy outcome was analyzed in
      terms of: fetal loss, preterm delivery (<=34 gestational weeks), fetal
      intrauterine growth restriction (IUGR), birth weight <2500 g and preeclampsia.
      Week at delivery, neonatal birth weight and neonatal birth weight percentile were
      also investigated. Hypocomplementemia, positivity for anti-dsDNA and triple
      positivity for antiphospholipid antibodies (aPL) were related to pregnancy
      outcome. RESULTS: Forty-three pregnancies ended in live births with a fetal loss
      rate of 8.5%. Fetal death, preterm delivery and birth weight <2500 g were
      associated with hypocomplementemia (p = 0.019, p = 0.0002, p < 0.0001
      respectively). Lower neonatal birth weight, lower neonatal birth weight
      percentile and lower week at delivery were associated with hypocomplementemia (p
      < 0.0001, p = 0.0003, p < 0.0001 respectively) and with triple aPL positivity (p
      = 0.008, p = 0.014, p = 0.03 respectively). A poor pregnancy outcome was
      confirmed among primary APS (PAPS) pregnancies with hypocomplementemia.
      Multivariate analysis confirmed that hypocomplementemia was an independent
      predictor of lower neonatal birth weight (p = 0.0001) and lower week at delivery
      (p = 0.002). CONCLUSION: Hypocomplementemia could be considered a novel
      prognostic factor for pregnancy outcome in APS patients.

PMID- 22635231
TI  - Soluble CD146 and APS: a potential biomarker of obstetrical complications?
AB  - Obstetric antiphospholipid syndrome (APS) seems to be a clinical subset of
      classical APS, for which the search for new markers is still challenging. Soluble
      CD146 (sCD146) constitutes a circulating endothelial biomarker. sCD146 is
      involved in the inflammatory response by promoting monocyte transmigration and
      displays chemotactic and angiogenic properties on endothelial cells. Its
      detection in human sera reveals physiological variations related to age and sex.
      A wide variation of sCD146 has been reported in several conditions. In
      particular, sCD146 levels are significantly higher in women presenting a history
      of recurrent fetal losses.

PMID- 22635233
TI  - Circulating beta2 glycoprotein I-IgG anti-beta2 glycoprotein I immunocomplexes in
      patients with definite antiphospholipid syndrome.
AB  - Beta2-glycoprotein I (beta(2)GPI), a relevant antigen in Antiphospholipid
      Syndrome (APS), binds anionic macromolecules including heparin (Hep). A possible
      formation of ternary complexes between beta(2)GPI, antibodies and Hep in APS is
      thus possible. The aim of this study was to evaluate Hep-beta(2)GPI interaction
      in patients with APS. The affinity of Heps of different length, including
      unfractionated Hep (UFH), low-molecular weight Hep (enoxaparin) and
      pentasaccharide (fondaparinux), to human beta(2)GPI was estimated by fluorescence
      spectroscopy, yielding dissociation constant (K(d)) values of 1.1, 24.0 and 89.4
      uM, demonstrating that the longer UFH binds to beta(2)GPI far more tightly than
      the shorter ones. Plasma and protein G-purified IgGs from eight patients with APS
      (i.e. five with thromboembolic disease and three with catastrophic APS), were
      fractionated by affinity chromatography using a Hep (UFH)-bound column, eluted
      with a linear NaCl gradient. For each chromatographic analysis, fractions were
      collected in the whole NaCl gradient and tested by ELISA for the presence of
      beta(2)GPI and anti-beta(2)GPI IgG. The results of Hep-affinity chromatography
      and ELISAs concurrently indicate that either beta(2)GPI and anti-beta(2)GPI IgG
      elute from the Hep column in the same chromatographic peak, at a retention time
      identical to that of the purified, isolated beta(2)GPI, thus suggesting that
      circulating immunocomplexes containing beta(2)GPI are present in patients with
      APS.

PMID- 22635232
TI  - Autoantibodies against galectin-2 peptides as biomarkers for the antiphospholipid
      syndrome.
AB  - Autoantibodies against opsonins of dying and dead cells mediate Fcgamma receptor
      dependent phagocytosis of autologous apoptotic and necrotic cells and hereby tend
      to elicit inflammation instead of silent clearance. We analysed sera of patients
      with chronic autoimmune diseases for the occurrence of IgG autoantibodies
      recognizing galectins. These pluripotent effectors can also bind to apoptotic or
      necrotic cells. Patients with antiphospholipid syndrome (APS; n = 104) and
      systemic lupus erythematosus (SLE; n = 62) were examined, healthy donors (n = 31)
      served as controls. Selected peptides of galectin (Gal)-2 were employed for
      peptide-based ELISAs. Levels of anti-Gal-2(PEP)-IgG were significantly increased
      in SLE and APS when compared with controls. In addition, patients with APS showed
      significantly higher levels of anti-Gal-2(PEP)-IgG compared with patients with
      SLE. Anti-Gal-2(PEP)-IgG may, therefore, be considered novel biomarkers for APS.

PMID- 22635234
TI  - Antiphosphatidylserine/prothrombin antibodies in primary antiphospholipid
      syndrome.
AB  - Antiprothrombin (aPT) antibodies may be detected by an enzyme-linked
      immunosorbent assay (ELISA) using a purified antigen or a
      phosphatidylserine/prothrombin complex (aPS/PT). IgG/IgM antibodies directed
      against aPS/PT were assessed in 158 patients with primary antiphospholipid
      syndrome (PAPS). They were detected in 80/158 (50.6%) PAPS patients; IgG alone
      was positive in 12 (7.6%), IgM alone in 36 (22.8%), and both IgG and IgM isotypes
      in 32 (20.2%) PAPS patients. IgG and IgM aPS/PT were significantly associated
      with both vascular thrombosis and pregnancy morbidity. IgG aPS/PT was
      significantly associated with venous thrombosis (p = 0.023), whilst IgG and IgM
      aPS/PT were associated with arterial thrombosis (p < 0.001 and p < 0.001,
      respectively). Logistic regression analysis showed that IgM and IgG aPS/PT were
      independent risk factors for thrombosis (odds ratio (OR) 3.5 [95% confidence
      interval (CI) 1.6-7.9] and OR 4.1 [95% CI 1.4-11.7], respectively) and IgM aPS/PT
      was an independent risk factor for arterial thrombosis (OR 2.7 [95% CI 1.1-6.7]).
      In conclusion, these findings indicate that aPS/PT are clinically relevant in
      PAPS.

PMID- 22635235
TI  - Antibodies to phosphatidylserine/prothrombin complex as an additional diagnostic
      marker of APS?
AB  - Antiprothrombin antibodies can be measured by ELISA using either a
      prothrombin/phosphatidylserine complex (aPS/PT) or prothrombin alone (aPT) as
      antigen. We aimed to compare the clinical features of autoimmune patients with
      avidity of aPS/PT and determine the diagnostic efficiency of aPS/PT and aPT for
      assessing antiphospholipid syndrome (APS). aPS/PT were of low (n = 9),
      heterogeneous (n = 31) and high (n = 8) avidity out of 48 cases. None of the
      samples with low avidity were positive in aPT ELISA. Among patients with
      heterogeneous or high avidity aPS/PT, there was a significantly greater number of
      patients with APS as compared to patients with low avidity (38/39 vs. 7/9; p <
      0.05). No SLE patients had high avidity antiprothrombin antibodies.

PMID- 22635236
TI  - Occurrence of selected antiphospholipid antibodies in offspring born from mothers
      with autoimmunity.
AB  - Autoimmune diseases can be accompanied by presence of various antiphospholipid
      antibodies (aPL). The laboratory criteria of antiphospholipid syndrome are based
      on detection of anticardiolipin, lupus anticoagulant or to antibeta2-
      glycoprotein I but currently a significance of other multiple aPL is being
      discussed. Because of their vascular and neuroinflammatory effect aPL, if being
      transplacentally transferred, might inflict damage in developing organism. The
      aim of our study was to determine the occurrence of eight selected aPL in
      offspring of mothers with proven autoimmune disease with aPL positivity. The
      possible influence of aPL presence on clinical, ultrasound and laboratory outcome
      of children was observed as well. The prospective study included 38 women: 17
      women with primary antiphospholipid syndrome and 21 women with other diagnosed
      autoimmune disease with detected aPL. Also included were 39 children born to the
      above mentioned mothers between January 2009 and April 2010 in Perinatology
      Centre in Pilsen, Czech Republic. The control group consisted of 30 mothers
      without AD and their 30 healthy singletons. Preliminary results of the study
      showed the presence of aPL in 42.1% neonates of aPL positive mothers with
      autoimmune disease, six month later aPL were present in only 37.5 % of these
      children. Observed occurrence of aPL positivity at 6 months of age in originally
      negative offspring could be attributed to vaccination or food exposure.
      Psychomotor development of children has proceeded without major deviations. The
      follow-up study continues and will evaluate both groups of children at two years
      of age.

PMID- 22635237
TI  - The annexin A5 protective shield model revisited: inherited carriage of the
      M2/ANXA5 haplotype in placenta as a predisposing factor for the development of
      obstetric antiphospholipid antibodies.
AB  - This concise review summarizes the role of reduced ANXA5 expression through
      carriage of the M2/ANXA5 haplotype as a predisposing factor for various
      thrombophilia related obstetric complications. A revised ANXA5 'protective
      shield' model is emphasized, where decreased coverage resulting of M2 carriage at
      placental villi could lead directly to the observed pathology and on the other
      hand through exposing of antiphospholipid antigenic determinants, to the
      development of antiphospholipid antibodies (aPL). The aPL then can further
      disrupt the ANXA5 protective shield. Available and prospective evidence for this
      revised model is discussed. Conclusions are made about the diagnostic
      implications of M2 carriage and possible therapeutic strategies with
      anticoagulants, proven successful in obstetric antiphospholipid syndrome (APS)
      treatment.

PMID- 22635238
TI  - Anti-cardiolipin and anti-beta2-glycoprotein I antibodies: normal reference
      ranges in northwestern Italy.
AB  - Laboratory tests for anticardiolipin antibodies (aCL) and anti-beta2glycoprotein
      I antibodies (a-beta2GPI) face problems common to many autoantibody assays: the
      lack of a reference standard and the need for each laboratory to assess assay
      specific cut-off values. The aims of the study were to evaluate the reference
      range upper limits (99th percentile) used for aCL and a-beta2GPI in the northwest
      of Italy and to investigate the analytical performances of these assays with the
      newly obtained reference ranges. We assayed aCL and a-beta2GPI in 104 serum
      samples from patients without a history of thrombosis, pregnancy morbidity,
      tumours, infections and/or autoimmune diseases (30 males and 74 non-pregnant
      females). We tested all the commercial assays available in our regions (i.e.
      Orgentec Diagnostika, Aesku Diagnostics and Inova Diagnostics ELISA; CliA Zenit
      RA and EliA Phadia Laboratory Systems). A further 30 serum samples, including 10
      from healthy subjects, 10 from antiphospholipid syndrome (APS) patients and 10
      from septic patients were assessed to investigate the analytical performance of
      the obtained cut-off limits. Reference range upper limits obtained with the
      commercial kits differ among assays and from the values reported by the
      manufacturer. Moreover, normal reference ranges calculated for IgG and IgM aCL
      differed from the arbitrary selected laboratory classification values suggested
      in the guidelines of 40 GPL and MPL.

PMID- 22635239
TI  - Studies of microparticles in patients with the antiphospholipid syndrome (APS).
AB  - OBJECTIVES: To study circulating platelet, monocyte and endothelial
      microparticles (PMPs, MMPs and EMPs) in patients with antiphospholipid syndrome
      (APS) in comparison with healthy controls. MATERIAL AND METHOD: Fifty-two
      patients with APS and 52 healthy controls were investigated. MPs were measured on
      a flow cytometer (Beckman Gallios) and defined as particles sized < 1.0 um,
      negative to phalloidin, positive to lactadherin and positive to either CD42a
      (PMPs), CD144 (EMPs) or CD14 (MMPs). Exposure of CD142 (TF) was measured on CD144
      positive MPs. RESULTS: Total number of MPs (i.e. lactadherin positive particles)
      was higher in APS patients versus controls (p < 0.001). An increased number of
      EMPs (p < 0.001), increased TF-positive EMPs (p < 0.001) and increased MMPs (p <
      0.001) were also observed. PMP numbers did not differ between the groups. None of
      the MP types differed in numbers between obstetric and thrombotic APS patients.
      CONCLUSION: We observed a high number of EMPs expressing TF in APS patients. The
      numbers of MMPs and total EMPs were also higher as compared with healthy controls
      but in contrast to previous reports, the number of PMPs did not differ between
      groups.

PMID- 22635240
TI  - Antiphospholipid syndrome in northwest Italy (APS Piedmont Cohort): demographic
      features, risk factors, clinical and laboratory profile.
AB  - We report the experience from the Antiphospholipid Antibodies (aPL) Regional
      Consortium in northwest Italy, meant to support clinical research and foster
      collaboration among health professionals regarding the diagnosis and management
      of antiphospholipid syndrome (APS) patients. This cohort-study (APS Piedmont
      Cohort) was designed to register the clinical characteristics at inception and
      associated immunological manifestations at diagnosis (if any) of patients who
      strictly fulfilled the current criteria for APS, all recruited at the Piedmont
      and Valle d'Aosta regions. Clinical and laboratory data from 217 APS patients
      (171 with vascular events, 33 with pregnancy morbidity and 13 with both), from 16
      centres within the geographical area were collected. Venous thrombosis was
      recorded in 45.6% of patients, arterial thrombosis in 35%, small-vessel
      thrombosis in 1.12% and mixed arterial and venous thrombosis in the remaining
      19.4% of the cases. Pregnancy morbidity included 19 patients with unexplained
      fetal death beyond the 10th week of pregnancy, 17 with premature birth before the
      34th week and 10 with three or more unexplained spontaneous abortions before the
      10th week of gestation. This consortium represents an instrument by which to
      audit clinical practice, to provide counselling to local centres and to sustain
      future basic and clinical APS research.

PMID- 22635241
TI  - Hypertension negatively affects the pregnancy outcome in patients with
      antiphospholipid syndrome.
AB  - The impact of hypertension in the pregnancies from autoimmune patients is not
      unequivocally defined. We have prospectively followed 168 pregnancies from 135
      patients from four Italian centres to verify the potential impact of hypertension
      in the antiphospholipid syndrome (APS). The rate of preeclampsia, mean neonatal
      weight and gestational age at delivery were significantly lower in patients with
      both APS and hypertension than in patients with hypertension or APS alone. This
      information may be relevant for counselling and care of these patients.

PMID- 22635242
TI  - Children's emotional adaptation to parental BMT.
AB  - Few studies have examined the effect of parental BMT on the family and less is
      known regarding the impact on children. The purpose of this prospective study was
      to increase understanding of children's adaptation to the stress of parental BMT
      across a 12-month trajectory. Data were obtained from 61 children ages 10-18
      before parental transplant, during parental hospitalization, 1, 4 , 8 and 12
      months post BMT. Mixed linear modeling was used to analyze longitudinal data from
      children nested within families. Analyses examined change in child emotional
      adaptation, points of greatest vulnerability throughout the BMT trajectory and
      the impact of theoretically relevant variables on their adaptation. Children's
      emotional adaptation became significantly more positive over time, although their
      level of distress remained above the norm. Pre-transplant was the period of
      greatest emotional distress. Negative self-esteem, disruption within the family
      structure, use of disengagement coping and the mother as transplant recipient
      were associated with more negative adaptation. Further research is needed to
      fully understand the effects of parental BMT on children. However, these findings
      point to the importance of considering the adaptation of children and its
      implications for the development of preventive family interventions for this
      vulnerable population.

PMID- 22635243
TI  - A novel protocol for haploidentical hematopoietic SCT without in vitro T-cell
      depletion in the treatment of severe acquired aplastic anemia.
AB  - Mismatched related donors of hematopoietic SCT (HSCT) for severe aplastic anemia
      (SAA) present challenges mainly associated with graft failure and GVHD. The
      greater the HLA disparity, the poorer the OS. About 19 consecutive SAA/very SAA
      (VSAA) patients who received HSCT from haploidentical family donors in our center
      are reported in this study, 18/19 pairs had 2-3 loci mismatched. All 19 cases
      failed to respond to previous therapy and were heavily transfused before
      transplantation. The conditioning regimen before HSCT included BU, CY and
      thymoglobulin. The recipients received CsA, mycophenolate mofetil (MMF) and short
      term MTX for GVHD prophylaxis. The source of stem cell grafts was a combination
      of G-CSF-primed BM and G-CSF-mobilized peripheral blood stem cells. All patients
      achieved 100% donor myeloid engraftment; the median time for myeloid engraftment
      was 12 days (ranging from 10-29 days) and for platelets was 18 days (ranging from
      8-180 days) with a cumulative platelet engraftment incidence of 84.21 +/- 10.53%.
      The cumulative incidence was 42.1 +/- 11.3% for grade II-IV acute GVHD and 56.2
      +/- 12.4% for chronic GVHD. The OS was 64.6 +/- 12.4% with a median 746-day (90
      1970) follow-up for surviving patients. These limited retrospective analysis data
      suggest that HLA-haploidentical HSCT for SAA patients without an HLA-identical
      sibling donor might be feasible. Further research to increase OS by decreasing
      GVHD while maintaining stable engraftment will be needed in the future.

PMID- 22635244
TI  - The impact of prior invasive mold infections in leukemia patients who undergo
      allo-SCT in the era of triazole-based secondary prophylaxis.

PMID- 22635245
TI  - Stenotrophomonas maltophilia infection in hematopoietic SCT recipients: high
      mortality due to pulmonary hemorrhage.
AB  - To clarify the clinical features and outcome of Stenotrophomonas maltophilia
      infection among hematopoietic SCT (HCT) recipients, we retrospectively reviewed
      the records of 1085 consecutive HCT recipients and identified 42 episodes in 31
      HCT recipients with S. maltophilia infection. We compared these recipients with
      30 non-HCT patients with S. maltophilia infection. The mortality rate in HCT
      recipients was significantly higher than that in non-HCT patients (relative risk
      5.7, P=0.04), and we identified seven patients with pulmonary hemorrhage due to
      S. maltophilia, exclusively in the HCT cohort. Six of these latter seven patients
      died within 1 day from the onset of hemorrhage and the isolate was identified
      after death in most cases; one patient, who received empiric therapy for S.
      maltophilia and granulocyte transfusion, survived for more than 2 weeks. The
      patients with pulmonary hemorrhage had a more severe and longer duration of
      neutropenia, persistent fever despite of the use of broad-spectrum antibiotics,
      complication by pneumonia and higher C-reactive protein levels than those without
      pulmonary hemorrhage. In conclusion, S. maltophilia was associated with fulminant
      and fatal pulmonary hemorrhage in HCT recipients. Empiric therapy with
      antibiotics before the onset of pulmonary hemorrhage may be effective in HCT
      recipients who carry the conditions identified.

PMID- 22635246
TI  - The significant impact of acute kidney injury on CKD in patients who survived
      over 10 years after myeloablative allogeneic SCT.
AB  - There are no well-defined studies of chronic kidney disease (CKD) among long-term
      survivors after hematopoietic SCT. A retrospective longitudinal study was
      conducted to characterize CKD in 77 subjects that had undergone myeloablative
      allogeneic SCT, all of whom had their serum creatinine (Cr) levels followed-up
      during the 10-year period after SCT. Their mean (range) survival time was 14.4
      (10.5-20.2) years. CKD was defined as a persistent decrease in the Cr-based
      estimated glomerular filtration rate to below 60 mL/min/1.73 m2. Acute kidney
      injury (AKI) was defined as an increase in Cr within the first 100 days after
      SCT, and its severity was classified into three stages according to the AKIN
      criteria. Kaplan-Meier and Cox proportional hazards regression analyses evaluated
      the association between AKI and the incidence of CKD. The cumulative incidence of
      CKD increased over time and reached 34% at 10 years. After adjusting for known
      risks for post-SCT CKD, each AKIN stage was strongly associated with the
      incidence of CKD. The incidence of CKD probably increases over time among
      subjects who are alive at >10 years after SCT. This study places a new emphasis
      on AKI as an important risk factor for CKD in post-SCT subjects.

PMID- 22635247
TI  - Tandem high-dose chemotherapy and autologous stem cell transplantation in
      patients with high-risk neuroblastoma: results of SMC NB-2004 study.
AB  - From January 2004 to December 2008, 50 consecutive patients with high-risk
      neuroblastoma were assigned to receive tandem HDCT (high-dose chemotherapy)/auto
      SCT after nine cycles of induction chemotherapy. CEC (carboplatin + etoposide +
      cyclophosphamide) regimen and TM (thiotepa + melphalan)-TBI regimen (or TM
      regimen for stage 3 patients) were the first and second HDCT regimens. Local
      radiotherapy, differentiation therapy with 13-cis-retinoid acid and immunotherapy
      with interleukin-2 were given after tandem HDCT/auto-SCT. Of the 50 patients, 49
      underwent a first HDCT/auto-SCT and 47 underwent a second HDCT/auto-SCT. The
      tumor relapsed or progressed in 14 patients, secondary malignancy developed in
      one patient and one patient died from chronic lung disease. Therefore, 34
      patients remained event free with a median follow-up of 54.5 months (range, 14-94
      months) from diagnosis. The probabilities of 5-year OS and EFS for all 50
      patients were 77.0% (95% confidence interval (CI), 63.7-90.3) and 71.4% (95% CI,
      58.7-84.1), respectively. However, all patients who remained event free for >3
      years after tandem HDCT/auto-SCT experienced late adverse effects.
      Chemotherapeutic dose-escalation strategy using tandem HDCT/auto-SCT was very
      encouraging for survival. However, further studies incorporating newer treatment
      modalities are needed to reduce late adverse effects without jeopardizing the
      survival rate.

PMID- 22635248
TI  - Qualifications and training of adult stem cell donor recruiters: recommendations
      by the World Marrow Donor Association.

PMID- 22635249
TI  - PABP and the poly(A) tail augment microRNA repression by facilitated miRISC
      binding.
AB  - Polyadenylated mRNAs are typically more strongly repressed by microRNAs (miRNAs)
      than their nonadenylated counterparts. Using a Drosophila melanogaster cell-free
      translation system, we found that this effect is mediated by the poly(A)-binding
      protein (PABP). miRNA repression was positively correlated with poly(A) tail
      length, but this stimulatory effect on repression was lost when translation was
      repressed by the tethered GW182 silencing domain rather than the miRNA-induced
      silencing complex (miRISC) itself. These findings are mechanistically explained
      by a notable function of PABP: it promotes association of miRISC with miRNA
      regulated mRNAs. We also found that PABP association with mRNA rapidly diminished
      with miRISC recruitment and before detectable deadenylation. We integrated these
      data into a revised model for the function of PABP and the poly(A) tail in miRNA
      mediated translational repression.

PMID- 22635250
TI  - Reducing bias in the assessment of treatment effectiveness: androgen deprivation
      therapy for prostate cancer.
AB  - BACKGROUND: Indication bias is the major challenge in assessing treatment
      effectiveness in observational studies. We explored the potential advantages of
      using an instrumental variable approach in the context of primary androgen
      deprivation therapy (ADT) for prostate cancer. METHODS: We identified 31,930 men
      in the linked Surveillance, Epidemiology, and End Results-Medicare database with
      a diagnosis of prostate cancer who were not treated definitively with radical
      prostatectomy or radiation in the years 1992 through 2002, with follow-up through
      2005. The association between use of primary ADT and overall, prostate cancer
      specific, and nonprostate cancer survival was assessed using multivariable
      regression and instrumental variable methods. Two instrumental variables, based
      on region and urologist prescribing preference, were constructed and analyzed
      using exogenous probit models. Prespecified subgroup analyses in patients with
      lower-risk and higher-risk prostate tumors were also carried out. RESULTS: In the
      overall cohort, standard multivariable regression analyses showed a significantly
      increased risk of prostate cancer-related death, whereas the instrumental
      variable approaches showed a protective effect of primary ADT, which was
      significant for the urologist preference instrument (hazard ratio: 0.74; 95%
      confidence interval, 0.60-0.93). In the high-risk subgroup, using urologist
      preference for primary ADT as the instrument, there was a significant reduction
      in overall mortality (hazard ratio: 0.75; 95% confidence interval, 0.57-0.99),
      driven by a large reduction in prostate cancer-specific mortality. CONCLUSIONS:
      Instrumental variable analysis appears to provide better control of bias when
      assessing the effectiveness of primary ADT for prostate cancer, although the
      results may be more applicable to policy rather than to clinical decisions.

PMID- 22635251
TI  - Mapping health status measures to a utility measure in a study of nursing home
      residents with advanced dementia.
AB  - BACKGROUND: Nursing home residents with advanced dementia commonly experience
      burdensome and costly interventions (eg, hospitalization) of questionable
      clinical benefit. To facilitate cost-effectiveness analyses of these
      interventions, utility-based measures are needed in order to estimate quality
      adjusted outcomes. METHODS: Nursing home residents with advanced dementia in 22
      facilities were followed for 18 months (N=319). Validated health status measures
      ascertained from nurses at baseline, quarterly, and death (N=1702 assessments)
      were mapped to the Health Utilities Index Mark 2 [range, 1 (perfect health) to 0
      (death); scores below 0 indicate states worse than death]. To assess validity,
      utility scores were compared between residents who did and did not receive
      burdensome interventions (parenteral therapy, percutaneous endoscopic gastrostomy
      tubes, and hospital transfers), residents with and without pneumonia, and
      residents who did and did not die at the last assessment. RESULTS: Mean (+/-SD)
      Health Utilities Index Mark 2 utility score for the cohort was 0.165+/-0.060
      (range, -0.005 to 0.215). Residents spent an average of 15.5% of their days with
      utilities <0.10. Lower utility scores were found among residents who received
      burdensome interventions (0.152+/-0.067 vs. 0.171+/-0.056; P=0.0003); had
      pneumonia (0.147+/-0.066 vs. 0.170+/-0.057; P=0.003); and were dying (0.163+/
      0.057 vs. 0.180+/-0.055; P=0.006). CONCLUSIONS: It is feasible to map health
      status measures to utility-based measures for advanced dementia. This work will
      facilitate future cost-effectiveness analyses aimed at quantifying the cost of
      interventions relative to quality-based outcomes for patients with this
      condition.

PMID- 22635252
TI  - Multiple gliomas: a case review.
AB  - BACKGROUND: Multiple gliomas, although a rare finding, can present with a
      clinical and radiological picture similar to that of metastatic disease,
      abscesses, lymphoma and demyelination. CASE REPORT: We report a rare case of
      multiple gliomas located in the left cerebral hemisphere, with a complex
      presentation emulating other possible differential diagnoses. CONCLUSION:
      Multiple gliomas should be taken into consideration as part of the differential
      diagnosis of multiple parenchymal brain lesions. Certain imaging modalities and
      findings can be extremely valuable with obtaining a diagnosis, and the subsequent
      formulation of a therapeutic strategy.

PMID- 22635253
TI  - Mesoionic oxides: facile access from triazolium salts or triazolylidene copper
      precursors, and catalytic relevance.
AB  - Reaction of CsOH with triazolium salts affords mesoionic compounds containing an
      exocyclic oxygen; the same product is obtained by reaction of the corresponding
      Cu(I) triazolylidenes with CsOH and represents an unusual reactivity pattern of N
      heterocyclic carbene precursors that has implications for carbene copper
      catalyzed reactions.

PMID- 22635255
TI  - Analyzing the phenotypic and functional complexity of lymphocytes using CyTOF
      (cytometry by time-of-flight).

PMID- 22635256
TI  - Rotational dynamics of coumarin 153 in non-ionic mixed micelles of n-octyl-beta-D
      thioglucoside and Triton X-100.
AB  - Rotational diffusion of the neutral probe coumarin 153 has been examined in a
      mixed surfactant system containing n-octyl-beta-D-thioglucoside (OTG) and Triton
      X-100 (TX100), two non-ionic surfactants belonging to the alkyl glucoside and
      polyoxyethylene alkyl ether families, respectively. Both steady-state and time
      resolved fluorescence measurements indicate that the polarity of the dye
      decreases slightly as the amount of ethoxylated surfactant in the mixed micelle
      increases. This behaviour can be attributed to migration of the probe towards the
      inner region of the micellar palisade layer as a result of the increasing
      hydration induced by the presence of TX100. The anisotropy decay curves, r(t),
      were well fitted to a biexponential function, characterized by two
      reorientational times of the probe in the micellar pseudophase. The experimental
      data were analyzed on the basis of the two-step and wobbling-in-a-cone model, and
      the results obtained correlated with the changes that occur in the palisade layer
      of the mixed micelles due to the different structure and nature of the head
      groups of both surfactants. It was found that, although the average reorientation
      time of the probe molecule is almost unaffected with the participation of the
      ethoxylated surfactant, the observed increase in the generalized order parameter
      suggests a certain rise in the compactness of the mixed micelles.

PMID- 22635254
TI  - TLR2 signaling subpathways regulate TLR9 signaling for the effective induction of
      IL-12 upon stimulation by heat-killed Brucella abortus.
AB  - Brucella abortus is a Gram-negative intracellular bacterium that induces MyD88
      dependent IL-12 production in dentritic cells (DCs) and a subsequent protective
      Th1 immune response. Previous studies have shown that the Toll-like receptor 2
      (TLR2) is required for tumor-necrosis factor (TNF) production, whereas TLR9 is
      responsible for IL-12 induction in DCs after exposure to heat-killed Brucella
      abortus (HKBA). TLR2 is located on the cell surface and is required for optimal
      microorganism-induced phagocytosis by innate immune cells; thus, phagocytosis is
      an indispensable preliminary step for bacterial genomic DNA recognition by TLR9
      in late-endosomal compartments. Here, we hypothesized that TLR2-triggered signals
      after HKBA stimulation might cross-regulate TLR9 signaling through the indirect
      modulation of the phagocytic function of DCs or the direct modulation of cytokine
      gene expression. Our results indicate that HKBA phagocytosis was TLR2-dependent
      and an essential step for IL-12p40 induction. In addition, HKBA exposure
      triggered the TLR2-mediated activation of both p38 and extracellular signal
      regulated kinase 1/2 (ERK1/2). Interestingly, although p38 was required for HKBA
      phagocytosis and phagosome maturation, ERK1/2 did not affect these processes but
      negatively regulated IL-12 production. Although p38 inhibitors tempered both TNF
      and IL-12 responses to HKBA, pre-treatment with an ERK1/2 inhibitor significantly
      increased IL-12p40 and abrogated TNF production in HKBA-stimulated DCs. Further
      experiments showed that the signaling events that mediated ERK1/2 activation
      after TLR2 triggering also required HKBA-induced Ras activation. Furthermore, Ras
      guanine nucleotide-releasing protein 1 (RasGRP1) mediated the TLR2-induced ERK1/2
      activation and inhibition of IL-12p40 production. Taken together, our results
      demonstrated that HKBA-mediated TLR2-triggering activates both the p38 and ERK1/2
      signaling subpathways, which divergently regulate TLR9 activation at several
      levels to induce an appropriate protective IL-12 response.

PMID- 22635257
TI  - Bedbugs (Cimex lectularius): identifying and managing an infestation.

PMID- 22635258
TI  - International nursing partnerships.

PMID- 22635259
TI  - Understanding involuntary hospitalization and use of seclusion and restraint.

PMID- 22635263
TI  - Contraception for women over 40.
AB  - Nurse practitioners can help women 40 and older make contraceptive choices that
      are effective, safe, and appropriate. The noncontraceptive benefits of some
      methods may be particularly relevant to women in this age group. Providing women
      with information about continuing fertility as they approach menopause and when
      it is safe to discontinue contraception may help to reduce unplanned pregnancies.

PMID- 22635264
TI  - Managing asthma in Black children.
AB  - Black children bear a disproportionate burden of asthma when compared to other
      segments of the population. This study assessed the role of symptom scores,
      spirometry testing, and serum-specific immunoglobulin E in the primary care
      management of asthma in Black children.

PMID- 22635266
TI  - Quantitative nanoscale visualization of heterogeneous electron transfer rates in
      2D carbon nanotube networks.
AB  - Carbon nanotubes have attracted considerable interest for electrochemical,
      electrocatalytic, and sensing applications, yet there remains uncertainty
      concerning the intrinsic electrochemical (EC) activity. In this study, we use
      scanning electrochemical cell microscopy (SECCM) to determine local heterogeneous
      electron transfer (HET) kinetics in a random 2D network of single-walled carbon
      nanotubes (SWNTs) on an Si/SiO(2) substrate. The high spatial resolution of
      SECCM, which employs a mobile nanoscale EC cell as a probe for imaging, enables
      us to sample the responses of individual portions of a wide range of SWNTs within
      this complex arrangement. Using two redox processes, the oxidation of
      ferrocenylmethyl trimethylammonium and the reduction of ruthenium (III)
      hexaamine, we have obtained conclusive evidence for the high intrinsic EC
      activity of the sidewalls of the large majority of SWNTs in networks. Moreover,
      we show that the ends of SWNTs and the points where two SWNTs cross do not show
      appreciably different HET kinetics relative to the sidewall. Using finite element
      method modeling, we deduce standard rate constants for the two redox couples and
      demonstrate that HET based solely on characteristic defects in the SWNT side wall
      is highly unlikely. This is further confirmed by the analysis of individual line
      profiles taken as the SECCM probe scans over an SWNT. More generally, the studies
      herein demonstrate SECCM to be a powerful and versatile method for activity
      mapping of complex electrode materials under conditions of high mass transport,
      where kinetic assignments can be made with confidence.

PMID- 22635267
TI  - Functional modulation of a protein folding landscape via side-chain distortion.
AB  - Ultrahigh-resolution (< 1.0 A) structures have revealed unprecedented and
      unexpected details of molecular geometry, such as the deformation of aromatic
      rings from planarity. However, the functional utility of such energetically
      costly strain is unknown. The 0.83 A structure of alpha-lytic protease (alphaLP)
      indicated that residues surrounding a conserved Phe side-chain dictate a rotamer
      which results in a ~6 degrees  distortion along the side-chain, estimated to cost
      4 kcal/mol. By contrast, in the closely related protease Streptomyces griseus
      Protease B (SGPB), the equivalent Phe adopts a different rotamer and is
      undistorted. Here, we report that the alphaLP Phe side-chain distortion is both
      functional and conserved in proteases with large pro regions. Sequence analysis
      of the alphaLP serine protease family reveals a bifurcation separating those
      sequences expected to induce distortion and those that would not, which
      correlates with the extent of kinetic stability. Structural and folding kinetics
      analyses of family members suggest that distortion of this side-chain plays a
      role in increasing kinetic stability within the alphaLP family members that use a
      large Pro region. Additionally, structural and kinetic folding studies of mutants
      demonstrate that strain alters the folding free energy landscape by destabilizing
      the transition state (TS) relative to the native state (N). Although side-chain
      distortion comes at a cost of foldability, it suppresses the rate of unfolding,
      thereby enhancing kinetic stability and increasing protein longevity under harsh
      extracellular conditions. This ability of a structural distortion to enhance
      function is unlikely to be unique to alphaLP family members and may be relevant
      in other proteins exhibiting side-chain distortions.

PMID- 22635268
TI  - A thermodynamic definition of protein domains.
AB  - Protein domains are conspicuous structural units in globular proteins, and their
      identification has been a topic of intense biochemical interest dating back to
      the earliest crystal structures. Numerous disparate domain identification
      algorithms have been proposed, all involving some combination of visual intuition
      and/or structure-based decomposition. Instead, we present a rigorous,
      thermodynamically-based approach that redefines domains as cooperative chain
      segments. In greater detail, most small proteins fold with high cooperativity,
      meaning that the equilibrium population is dominated by completely folded and
      completely unfolded molecules, with a negligible subpopulation of partially
      folded intermediates. Here, we redefine structural domains in thermodynamic terms
      as cooperative folding units, based on m-values, which measure the cooperativity
      of a protein or its substructures. In our analysis, a domain is equated to a
      contiguous segment of the folded protein whose m-value is largely unaffected when
      that segment is excised from its parent structure. Defined in this way, a domain
      is a self-contained cooperative unit; i.e., its cooperativity depends primarily
      upon intrasegment interactions, not intersegment interactions. Implementing this
      concept computationally, the domains in a large representative set of proteins
      were identified; all exhibit consistency with experimental findings.
      Specifically, our domain divisions correspond to the experimentally determined
      equilibrium folding intermediates in a set of nine proteins. The approach was
      also proofed against a representative set of 71 additional proteins, again with
      confirmatory results. Our reframed interpretation of a protein domain transforms
      an indeterminate structural phenomenon into a quantifiable molecular property
      grounded in solution thermodynamics.

PMID- 22635269
TI  - Bacterial effector binds host cell adenylyl cyclase to potentiate Galphas
      dependent cAMP production.
AB  - Subversion of host organism cAMP signaling is an efficient and widespread
      mechanism of microbial pathogenesis. Bartonella effector protein A (BepA) of
      vasculotumorigenic Bartonella henselae protects the infected human endothelial
      cells against apoptotic stimuli by elevation of cellular cAMP levels by an as yet
      unknown mechanism. Here, adenylyl cyclase (AC) and the alpha-subunit of the AC
      stimulating G protein (Galphas) were identified as potential cellular target
      proteins for BepA by gel-free proteomics. Results of the proteomics screen were
      evaluated for physical and functional interaction by: (i) a heterologous in vivo
      coexpression system, where human AC activity was reconstituted under the
      regulation of Galphas and BepA in Escherichia coli; (ii) in vitro AC assays with
      membrane-anchored full-length human AC and recombinant BepA and Galphas; (iii)
      surface plasmon resonance experiments; and (iv) an in vivo fluorescence
      bimolecular complementation-analysis. The data demonstrate that BepA directly
      binds host cell AC to potentiate the Galphas-dependent cAMP production. As
      opposed to the known microbial mechanisms, such as ADP ribosylation of G protein
      alpha-subunits by cholera and pertussis toxins, the fundamentally different BepA
      mediated elevation of host cell cAMP concentration appears subtle and is
      dependent on the stimulus of a G protein-coupled receptor-released Galphas. We
      propose that this mechanism contributes to the persistence of Bartonella henselae
      in the chronically infected vascular endothelium.

PMID- 22635271
TI  - Salience driven value integration explains decision biases and preference
      reversal.
AB  - Human choice behavior exhibits many paradoxical and challenging patterns.
      Traditional explanations focus on how values are represented, but little is known
      about how values are integrated. Here we outline a psychophysical task for value
      integration that can be used as a window on high-level, multiattribute decisions.
      Participants choose between alternative rapidly presented streams of numerical
      values. By controlling the temporal distribution of the values, we demonstrate
      that this process underlies many puzzling choice paradoxes, such as temporal,
      risk, and framing biases, as well as preference reversals. These phenomena can be
      explained by a simple mechanism based on the integration of values, weighted by
      their salience. The salience of a sampled value depends on its temporal order and
      momentary rank in the decision context, whereas the direction of the weighting is
      determined by the task framing. We show that many known choice anomalies may
      arise from the microstructure of the value integration process.

PMID- 22635270
TI  - Single amino acid mutation in an ATP-binding cassette transporter gene causes
      resistance to Bt toxin Cry1Ab in the silkworm, Bombyx mori.
AB  - Bt toxins derived from the arthropod bacterial pathogen Bacillus thuringiensis
      are widely used for insect control as insecticides or in transgenic crops. Bt
      resistance has been found in field populations of several lepidopteran pests and
      in laboratory strains selected with Bt toxin. Widespread planting of crops
      expressing Bt toxins has raised concerns about the potential increase of
      resistance mutations in targeted insects. By using Bombyx mori as a model, we
      identified a candidate gene for a recessive form of resistance to Cry1Ab toxin on
      chromosome 15 by positional cloning. BGIBMGA007792-93, which encodes an ATP
      binding cassette transporter similar to human multidrug resistance protein 4 and
      orthologous to genes associated with recessive resistance to Cry1Ac in Heliothis
      virescens and two other lepidopteran species, was expressed in the midgut.
      Sequences of 10 susceptible and seven resistant silkworm strains revealed a
      common tyrosine insertion in an outer loop of the predicted transmembrane
      structure of resistant alleles. We confirmed the role of this ATP-binding
      cassette transporter gene in Bt resistance by converting a resistant silkworm
      strain into a susceptible one by using germline transformation. This study
      represents a direct demonstration of Bt resistance gene function in insects with
      the use of transgenesis.

PMID- 22635272
TI  - RNA 3'-end mismatch excision by the severe acute respiratory syndrome coronavirus
      nonstructural protein nsp10/nsp14 exoribonuclease complex.
AB  - The replication/transcription complex of severe acute respiratory syndrome
      coronavirus is composed of at least 16 nonstructural proteins (nsp1-16) encoded
      by the ORF-1a/1b. This complex includes replication enzymes commonly found in
      positive-strand RNA viruses, but also a set of RNA-processing activities unique
      to some nidoviruses. The nsp14 protein carries both exoribonuclease (ExoN) and
      (guanine-N7)-methyltransferase (N7-MTase) activities. The nsp14 ExoN activity
      ensures a yet-uncharacterized function in the virus life cycle and must be
      regulated to avoid nonspecific RNA degradation. In this work, we show that the
      association of nsp10 with nsp14 stimulates >35-fold the ExoN activity of the
      latter while playing no effect on N7-MTase activity. Nsp10 mutants unable to
      interact with nsp14 are not proficient for ExoN activation. The nsp10/nsp14
      complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a
      single mismatched nucleotide at the 3'-end mimicking an erroneous replication
      product. In contrast, di-, tri-, and longer unpaired ribonucleotide stretches, as
      well as 3'-modified RNAs, resist nsp10/nsp14-mediated excision. In addition to
      the activation of nsp16-mediated 2'-O-MTase activity, nsp10 also activates nsp14
      in an RNA processing function potentially connected to a replicative mismatch
      repair mechanism.

PMID- 22635274
TI  - Development of a short-form Learning Organization Survey: the LOS-27.
AB  - Despite urgent need for innovation, adaptation, and change in health care, few
      tools enable researchers or practitioners to assess the extent to which health
      care facilities perform as learning organizations or the effects of initiatives
      that require learning. This study's objective was to develop and test a short
      form Learning Organization Survey to fill this gap. The authors applied
      exploratory factor analysis and confirmatory factor analysis to data from
      Veterans Health Administration personnel to derive a short-form survey and then
      conducted further confirmatory factor analysis and factor invariance testing on
      additional Veterans Health Administration data to evaluate the short form.
      Results suggest that a 27-item, 7-factor survey (2 environmental factors, 1 on
      leadership, and 4 on concrete learning processes and practices) reliably measures
      key features of organizational learning, allowing researchers to evaluate
      theoretical propositions about organizational learning, its antecedents, and
      outcomes and enabling managers to assess and enhance organizations' learning
      capabilities and performance.

PMID- 22635273
TI  - Lysine-specific demethylase 2A (KDM2A) normalizes human embryonic stem cell
      derived keratinocytes.
AB  - Studies on human lysine-specific demethylase 2A (KDM2A) by others have recently
      begun. To date, the demethylase activity has been known to reduce expression of
      genes and eventually inhibit proliferation of cells. However, while attempting to
      improve proliferation of hES-cell-derived Nod keratinocytes, which grow poorly
      and have a short life span, we found that high expression of the KDM2A gene
      improves the poor proliferation of the cells. Of the four isomer cDNAs that we
      prepared from alternatively spliced KDM2A transcripts, only one stimulates the
      proliferation. This (KDM2A-N782) encodes the 782AA protein containing the JmjC,
      CXXC, and Ring domains, but not the F-box and AMN1 domains, unlike KDM2A, which
      has been studied by other groups. Our results not only show that differently
      spliced transcripts from a gene result in totally opposite outcomes, but also
      present critical evidence of the complicated activities of KDM2A, which contains
      all of the five domains.

PMID- 22635275
TI  - Pronounced pH effects on the kinetics of cucurbit[7]uril-based pseudorotaxane
      formation and dissociation.
AB  - Deprotonation of the two terminal COOH groups on a 4,4'-bipyridinium linear
      derivative leads to a pronounced slow down on the kinetics of threading and
      unthreading by the cucurbit[7]uril host.

PMID- 22635277
TI  - Irritable bowel syndrome: a holistic approach.

PMID- 22635276
TI  - Sumoylation of MDC1 is important for proper DNA damage response.
AB  - In response to DNA damage, many DNA damage factors, such as MDC1 and 53BP1,
      redistribute to sites of DNA damage. The mechanism governing the turnover of
      these factors at DNA damage sites, however, remains enigmatic. Here, we show that
      MDC1 is sumoylated following DNA damage, and the sumoylation of MDC1 at Lys1840
      is required for MDC1 degradation and removal of MDC1 and 53BP1 from sites of DNA
      damage. Sumoylated MDC1 is recognized and ubiquitinated by the SUMO-targeted E3
      ubiquitin ligase RNF4. Mutation of the MDC1 Lys 1840 (K1840R) results in impaired
      CtIP, replication protein A, and Rad51 accumulation at sites of DNA damage and
      defective homologous recombination (HR). The HR defect caused by MDC1K1840R
      mutation could be rescued by 53BP1 downregulation. These results reveal the
      intricate dynamics governing the assembly and disassembly of DNA damage factors
      at sites of DNA damage for prompt response to DNA damage.

PMID- 22635278
TI  - Discrepancies in end-of-life decisions between elderly patients and their named
      surrogates.
AB  - INTRODUCTION: This study aims to determine the attitudes of Asian elderly
      patients towards invasive life support measures, the degree of patient-surrogate
      concordance in end-of-life decision making, the extent to which patients desire
      autonomy over end-of-life medical decisions, the reasons behind patients' and
      surrogates' decisions, and the main factors influencing patients' and surrogates'
      decision-making processes. We hypothesize that there is significant patient
      surrogate discordance in end-of-life decision making in our community. MATERIALS
      AND METHODS: The patient and surrogate were presented with a hypothetical
      scenario in which the patient experienced gradual functional decline in the
      community before being admitted for life-threatening pneumonia. It was explained
      that the outcome was likely to be poor even with intensive care and each patient
      surrogate pair was subsequently interviewed separately on their opinions of
      extraordinary life support using a standardised questionnaire. Both parties were
      blinded to each other's replies. RESULTS: In total, 30 patients and their
      surrogate decision-makers were interviewed. Twenty-eight (93.3%) patients and 20
      (66.7%) surrogates rejected intensive care. Patient-surrogate concurrence was
      found in 20 pairs (66.7%). Twenty-four (80.0%) patients desired autonomy over
      their decision. The patients' and surrogates' top reasons for rejecting intensive
      treatment were treatment-related discomfort, poor prognosis and financial cost.
      Surrogates' top reasons for selecting intensive treatment were the hope of
      recovery, the need to complete final tasks and the sanctity of life. CONCLUSION:
      The majority of patients desire autonomy over critical care issues. Relying on
      the surrogates' decisions to initiate treatment may result in treatment against
      patients' wishes in up to one-third of critically ill elderly patients.

PMID- 22635279
TI  - Where do people with mental disorders in Singapore go to for help?
AB  - INTRODUCTION: This study aims to examine the pattern of services utilisation and
      the factors associated with help-seeking behaviour among those with mental
      disorders in the multi-ethnic Asian population of Singapore. MATERIALS AND
      METHODS: A household survey was carried out on a nationally representative sample
      of the adult (18 years and above) resident population. The main instrument used
      to establish the diagnosis of mental disorders and the services sought was the
      Composite International Diagnostic Interview version 3.0 (CIDI 3.0). The
      'services' component of the instrument contains questions, which examine service
      utilisation for mental health problems. RESULTS: A total number of 6616 completed
      respondents constituted a representative sample of the adult resident population
      in Singapore. Only 31.7% of those with mental disorders had sought help: 15.7%
      from mental health providers, 8.4% from general practitioners, and 7.6% from
      religious/ spiritual advisors or other healers. Among respondents with severe
      disability across any disorder assessed in our survey, 50.1% had sought help from
      some service in the past 12 months. Individuals with moderate or mild levels had
      lower rates of consultation, i.e. 35.4% and 30.6% respectively. The rate of using
      the Internet as a source of help was low in this population. CONCLUSION: There is
      a need to engage and work collaboratively with healthcare providers (including
      religious and spiritual healers) in the community to detect, assess and treat
      those with mental illness. More general practitioners need to be involved, and
      the role of the Internet also requires further consideration as a source for
      help.

PMID- 22635280
TI  - Effects of age and gender on left atrial ejection force and volume from real-time
      three-dimensional echocardiography.
AB  - INTRODUCTION: This study was carried out to (i) provide the methodology for
      determining left atrial (LA) volume, emptying fraction and ejection force (LAEF),
      from real-time 3-dimensional echocardiography (RT3DE), and (ii) evaluate the
      effects of age and gender on LA volume and LAEF in a wide age range of healthy
      participants. MATERIALS AND METHODS: RT3DE was performed in 102 healthy
      participants (age range, 20 to 80 years). From full-volume data sets, LA
      endocardial borders were automatically traced and LA volumes were determined.
      LAEF was calculated as 1/3*mitral annular area * (blood density) * (peak velocity
      of A wave)(2) according to Newton's law of motion and hydrodynamics; wherein the
      mitral annular area (MVA) is traced using RT3DE and A is the peak Doppler-derived
      blood velocity at atrial systole with the sample volume placed at the mitral
      annulus level. RESULTS: ANOVA analysis revealed that LA volume indices were
      significantly correlated with age (r = 0.366, P <0.0001 for maximal volume index
      and r = 0.288, P <0.005 for minimal volume index). LAEF was also significantly
      positively correlated with age (r = 0.49, P <0.0001). The LA emptying fraction
      was maintained across ages. LA volume indices and LAEF did not differ
      significantly with gender. CONCLUSION: Our data can be used as normal reference
      values for LA volumes and LAEF. We have demonstrated that age is positively
      related to LA volume indices and LAEF, which suggests that age-dependent cut-off
      values should be considered in those with heart disease.

PMID- 22635281
TI  - The hidden impact of childhood cancer on the family: a multi-institutional study
      from Singapore.
AB  - INTRODUCTION: The care of children with cancer creates emotional and financial
      hardships for their families. There is a lack of information on the impact of
      childhood cancer on the family as a whole in Singapore. Thus, we set out to
      assess the financial impact as well as its psychosocial impact in our local
      context. MATERIALS AND METHODS: All patients diagnosed and treated for cancer at
      the Departments of Paediatrics, KK Women's and Children's Hospital and National
      University Hospital, Singapore were eligible for this study. Families of these
      patients completed 2 self-administered questionnaires: (i) About-you and your
      family and (ii) the Impact-On-Family scale. For the latter, the total score was
      obtained by the summation of all scores, where high scores correlated to high
      impact. RESULTS: Seventy-nine parents were enrolled during the study period from
      October 2008 to February 2009. Being of Malay/Indian origin was associated with a
      high overall family burden. On the other hand, being of Malay/Indian origin was
      also associated with most successful at mastery when a child was diagnosed with
      cancer (P = 0.001). In addition, when compared to caregivers who remained
      employed, those who were asked to quit their job, experienced a higher Financial
      Burden (P = 0.03), a high Familial/Social Burden (P = 0.05) and a high Personal
      Strain (P = 0.03). CONCLUSION: Childhood cancer impacted family life in Singapore
      at many levels. In particular, the factors involved are various cultural
      discourses; employment status of caregivers; and those whose leave/pay are
      affected.

PMID- 22635282
TI  - Spontaneous cholesterol crystal embolism--a rare cause of renal failure.

PMID- 22635283
TI  - Lyme neuroretinitis in Singapore: a diagnostic dilemma.

PMID- 22635284
TI  - An unusual skin growth.

PMID- 22635286
TI  - Ethics guidelines in a widened context.

PMID- 22635285
TI  - The numeracy understanding in medicine instrument: a measure of health numeracy
      developed using item response theory.
AB  - BACKGROUND: Health numeracy can be defined as the ability to understand and apply
      information conveyed with numbers, tables and graphs, probabilities, and
      statistics to effectively communicate with health care providers, take care of
      one's health, and participate in medical decisions. OBJECTIVE: To develop the
      Numeracy Understanding in Medicine Instrument (NUMi) using item response theory
      scaling methods. DESIGN: A 20-item test was formed drawing from an item bank of
      numeracy questions. Items were calibrated using responses from 1000 participants
      and a 2-parameter item response theory model. Construct validity was assessed by
      comparing scores on the NUMi to established measures of print and numeric health
      literacy, mathematic achievement, and cognitive aptitude. PARTICIPANTS: Community
      and clinical populations in the Milwaukee and Chicago metropolitan areas.
      RESULTS: Twenty-nine percent of the 1000 respondents were Hispanic, 24% were non
      Hispanic white, and 42% were non-Hispanic black. Forty-one percent had no more
      than a high school education. The mean score on the NUMi was 13.2 (s = 4.6) with
      a Cronbach alpha of 0.86. Difficulty and discrimination item response theory
      parameters of the 20 items ranged from -1.70 to 1.45 and 0.39 to 1.98,
      respectively. Performance on the NUMi was strongly correlated with the Wide Range
      Achievement Test-Arithmetic (0.73, P < 0.001), the Lipkus Expanded Numeracy Scale
      (0.69, P < 0.001), the Medical Data Interpretation Test (0.75, P < 0.001), and
      the Wonderlic Cognitive Ability Test (0.82, P < 0.001). Performance was
      moderately correlated to the Short Test of Functional Health Literacy (0.43, P <
      0.001). LIMITATIONS: The NUMi was found to be most discriminating among
      respondents with a lower-than-average level of health numeracy. CONCLUSIONS: The
      NUMi can be applied in research and clinical settings as a robust measure of the
      health numeracy construct.

PMID- 22635287
TI  - The quandary of unrestorability.

PMID- 22635288
TI  - Emerging perspectives on adolescents and young adults with high-functioning
      autism spectrum disorders, violence, and criminal law.
AB  - As the prevalence of autism spectrum disorders (ASDs) has increased, attention
      has shifted toward consideration of ASDs in adolescence and adulthood, as well as
      public health repercussions for this population. Since the social and emotional
      deficits within ASDs may be salient during incidents of unintended criminal or
      violent behavior, one area of focus is involvement of adolescents and young
      adults with ASD in the criminal justice system. Without a thorough understanding
      of how and why individuals with ASDs may exhibit criminal behavior, judicial and
      legislative state systems have begun to develop policies lacking a substantial
      evidence base. In this article, we attempt to synthesize the literature on one
      type of ASD (high functioning) and criminal behavior. Three specific deficits
      characteristic of individuals with ASDs (theory of mind, emotion regulation, and
      moral reasoning) are examined as potential confluent forces leading to criminal
      behavior among individuals with ASDs. Legal and policy recommendations are
      presented.

PMID- 22635289
TI  - Commentary: Treatment and violence risk mitigation in high-functioning autism
      spectrum individuals.
AB  - The article by Lerner and colleagues will allow forensic clinicians to gain more
      understanding of how the specific cognitive deficits in persons with high
      functioning autism spectrum disorder (HFASD) relate to the propensity of these
      individuals to engage in cognitive distortions associated with violence. These
      deficits are relevant to a variety of forensic evaluations of matters such as
      criminal responsibility. We argue that they also have implications for the
      treatment and risk mitigation of individuals with HFASD who have engaged in
      violent behavior.

PMID- 22635290
TI  - Peer review committees and state licensing boards: responding to allegations of
      physician misconduct.
AB  - Although physicians tend to be more concerned about malpractice actions,
      adjudication of complaints of alleged physician misconduct by peer review
      organizations and state licensing authorities can have equally serious
      consequences. Unlike medical malpractice, no patient injury is necessary to
      support the claim of alleged misconduct. Unlike malpractice, in which a plaintiff
      must be the injured party, in administrative peer review, colleagues, family
      members, and patients may all qualify as potential complainants. Unlike
      malpractice, where the standard of care is what the average prudent practitioner
      would be expected to do in similar circumstances, in peer review, the standard of
      care is the code that the organization has endorsed and to which the individual
      practitioner has agreed by choosing to join the organization. Forensic
      psychiatrists who may serve either as experts for a peer review or state board
      investigation or as peer review committee members must understand the legal
      foundation of the process and the attendant psychological and sociopolitical
      forces affecting the different parties.

PMID- 22635291
TI  - Commentary: The case of Poliner v. Texas Health Systems.
AB  - Fear of litigious reprisal may deter potential peer reviewers from participation
      in the medical peer review process. The federal Health Care Quality Improvement
      Act of 1986, as elucidated in Poliner v. Texas Health Systems, encourages
      effective peer review by conferring immunity on peer reviewers, so long as they
      ensure adequate due process. The American Psychiatric Association's "Procedures
      for Handling Complaints of Unethical Conduct " offers a system for peer review
      that promotes improvements in quality of care, fairness to respondent physicians,
      and protection for peer reviewers.

PMID- 22635292
TI  - Clinical decision-making about inpatient violence risk at admission to a public
      sector acute psychiatric hospital.
AB  - This is an examination of the extent to which patients who are violent in the
      hospital can be distinguished from nonviolent patients, based on information that
      is readily available at the time of admission to a state acute psychiatric
      hospital. The charts of 235 inpatients were examined retrospectively, by
      selecting 103 patients who had engaged in inpatient violence and comparing them
      with 132 randomly selected patients who had not during the same period. Data were
      gathered from initial psychiatric assessment and admissions face sheets in
      patients' charts, reflecting information available to a mental health
      professional within the first 24 hours of a patient's admission. Multivariate
      analysis showed that violent and nonviolent patients were distinguished by
      diagnosis, age, gender, estimated intelligence, psychiatric history, employment
      history, living situation, and agitated behavior. These factors led to an 80
      percent correct classification of violent patients and thus may assist clinicians
      to structure decision-making about the risk of inpatient violence.

PMID- 22635293
TI  - Commentary: the value of the clinical interview.
AB  - The potential for violence among hospitalized psychiatric patients is not a new
      phenomenon. Risk prediction in hospitalized psychiatric patients requires, in
      addition to actuarial tools, a firsthand understanding of the patient's
      psychiatric disorder, symptoms, personality structure, coping skills, and defense
      mechanisms. The current state of psychiatric hospital care and treatment of
      mental illness appears to have arrived at such a point that some hospitals are
      inadequately staffed and unable to provide sufficient time for clinicians to
      interview newly admitted patients and gain as much information as possible. If an
      admission is meant to provide some treatment beyond rapid pharmacological
      stabilization, then there must be, beginning with admission, someone with the
      time, interest, and skill who talks with the patient to understand his problems
      and helps guide the subsequent treatment approach through to discharge. The
      author suggests that risk assessment and treatment, rather than risk prediction
      and management, should be the goals of hospitalization.

PMID- 22635294
TI  - Predictors of general and violent recidivism among SMI prisoners returning to
      communities in New York State.
AB  - Correctional and forensic mental health systems throughout the country are
      routinely called on to manage and provide treatment for mentally ill prison
      inmates. This study identifies criminal justice and mental health predictors of
      general re-arrest and re-arrest for violence in seriously mentally ill (SMI)
      persons leaving prison in New York State. Both length and diversity of criminal
      history predicted general re-arrest, as did substance abuse diagnoses,
      participation in community mental health treatment, parole supervision, and
      coordinated parole and mental health services. Only demographics and criminal
      justice measures were predictive of re-arrest for violence. The rate of re-arrest
      for violence in this SMI sample was lower than that of general prison release
      populations.

PMID- 22635295
TI  - Commentary: Toward an improved understanding of recidivism.
AB  - Setting out to identify predictors of recidivism in seriously mentally ill (SMI)
      persons who return to their community from prison, Hall and colleagues offer to
      the forensic community a substantive contribution to the organization of
      interventions aimed to promote both the social and the psychiatric recovery of
      these individuals and to reduce their rate of re-entry into the penal system.
      While their work in the field is praiseworthy, I would like to share my thoughts
      and considerations to stimulate a dialogue about a subject that should be of
      interest to both clinicians and policy makers.

PMID- 22635296
TI  - Medications for aggressiveness in prison: focus on oxcarbazepine.
AB  - The literature regarding the use of medication for impulsive aggression, both in
      a prison setting and outside of prison, is briefly reviewed. The rationale for
      using oxcarbazepine for impulsive aggression in prison is presented, focusing on
      the evidence (though limited) of efficacy, the lack of frequent significant side
      effects, and the cost/benefit ratio, compared with other options.

PMID- 22635297
TI  - Covert medication in psychiatric emergencies: is it ever ethically permissible?
AB  - Covert administration of medications to patients, defined as the administration
      of medication to patients without their knowledge, is a practice surrounded by
      clinical, legal, ethics-related, and cultural controversy. Many psychiatrists
      would be likely to advocate that the practice of covert medication in emergency
      psychiatry is not clinically, ethically, or legally acceptable. This article
      explores whether there may be exceptions to this stance that would be ethical. We
      first review the standard of emergency psychiatric care. Although we could
      identify no published empirical studies of covert administration of medicine in
      emergency departments, we review the prevalence of this practice in other
      clinical settings. While the courts have not ruled with respect to covert
      medication, we discuss the evolving legal landscape of informed consent,
      competency, and the right to refuse treatment. We discuss dilemmas regarding the
      ethics involved in this practice, including the tensions among autonomy,
      beneficence, and duty to protect. We explore how differences between cultures
      regarding the value placed on individual versus family autonomy may affect
      perspectives with regard to this practice. We investigate how consumers view this
      practice and their treatment preferences during a psychiatric emergency. Finally,
      we discuss psychiatric advance directives and explore how these contracts may
      affect the debate over the practice.

PMID- 22635298
TI  - On the roots of modern forensic psychiatry: ethics ramifications.
AB  - The historical origin of modern forensic psychiatry, as well as the circumstances
      of its evolution, may be defined and described from several vantage points. In
      this article I present a critical reading of Richard J. Bonnie's article,
      published in the Journal, in which he assigned the budding of modern forensic
      psychiatry to the 20th century. Although I concur with Bonnie's historical
      analysis, as well as with his underlying moral approach, I suggest that, to
      attain a broader view of the contribution of forensic psychiatry, it is important
      to be open to additional narratives of its development. The supplemental
      narrative that I offer highlights values other than those that were highlighted
      by Bonnie that are deeply rooted and equally inherent in the practice of forensic
      psychiatry. Thus, awareness of the two complementary narratives enables a
      stereoscopic view that encompasses the full picture regarding the roots of
      forensic psychiatry.

PMID- 22635299
TI  - Washington's Senate Bill 6610 on transferring provisions for persons found not
      guilty by reason of insanity.
AB  - In Washington state, public concern about the potential dangerousness of mentally
      ill offenders has led to increasing legislative efforts to contain them in secure
      settings. A recently enacted law authorizes the transfer of persons found not
      guilty by reason of insanity from state psychiatric hospitals to prison
      facilities. The authors review the recent legislation and discuss some of the
      legal, policy, and clinical ramifications of the law.

PMID- 22635300
TI  - Forty years after Jackson v. Indiana: states' compliance with "reasonable period
      of time" ruling.
AB  - In Jackson v. Indiana (1972) the U.S. Supreme Court held that states may not
      indefinitely confine criminal defendants solely on the basis of incompetence to
      stand trial. The Court ruled that the commitment duration be limited based on the
      likelihood of restorability, but did not provide specific time limits. Nearly
      four decades later, there is striking heterogeneity regarding the length of
      confinement. As of 2007, 28 percent of the states specify 1 year or less, 20
      percent specify 1 to 10 years, 22 percent link the limit to the criminal penalty
      for the charged offense (up to life), and 30 percent set no limit. Thus, most
      state statutes seem out of compliance with Jackson. While research has focused on
      predicting restorability and testing restoration modalities, empirical evidence
      about the reasonable length of time to determine restorability has not been
      adequately addressed. Quantitative analysis of Jackson's reasonable period of
      time is needed to ensure due process for incompetent felony defendants.

PMID- 22635301
TI  - Mental health legislation in Ireland: a lot done, more to do.
AB  - Mental health legislation is necessary to protect the rights of people with
      mental disorders, a vulnerable section of society. Ireland's new Mental Health
      Act 2001 was fully implemented in 2006 with the intent of bringing Irish
      legislation more in line with international standards, such as the European
      Convention on Human Rights and United Nations Principles for the Protection of
      Persons with Mental Illness. The new legislation introduced several important
      reforms in relation to involuntary admission, independent reviews of involuntary
      detention, consent to treatment, and treatment of children and adolescents. It
      also presented significant challenges in terms of service delivery and resources
      within Irish mental health services. Both mental health service users and
      providers reported a range of difficulties with the new legislation. In this
      article, we analyze the Irish Mental Health Act focusing on the enhanced
      protection that it provides for patients, but also highlighting some areas of
      concern such as the conduct of mental health tribunals, consent and capacity
      problems, resource allocation, and disruptions in mental health service delivery.

PMID- 22635302
TI  - The forensic and legal implications of water, wet, or fry.
AB  - Embalming fluid applied to marijuana cigars or cigarettes, with or without the
      addition of phencyclidine (PCP), has several names, such as water, wet, illy, and
      fry. Individuals who commit crimes under the influence of this substance are
      often violent and may appear psychotic, with symptoms resembling schizophrenia or
      delirium. Currently, there are no case reports or case law involving the use of
      this substance. Wet may impair one's competency to stand trial (CST). The authors
      present a composite case of a man who abused wet for three years and had been
      sober for three months when he presented for a CST evaluation. The authors posit
      that individuals who use wet may raise settled (fixed) insanity or defenses of
      not guilty by reason of insanity in the future.

PMID- 22635303
TI  - An increasingly problematic situation in Georgia regarding difficulty in
      rebutting defense testimony on battered person syndrome (BPS).

PMID- 22635304
TI  - Egg activation in physiological polyspermy.
AB  - Fertilization is indispensable not only for restoring diploid genomes but also
      for the initiation of early embryonic cell cycles in sexual reproduction. While
      most animals exhibit monospermy, which is ensured by polyspermy blocks to prevent
      the entry of extra sperm into the egg at fertilization, several animals exhibit
      physiological polyspermy, in which the entry of several sperm is permitted but
      only one sperm nucleus participates in the formation of a zygote nucleus.
      Polyspermy requires that the sperm transmit the egg activation signal more
      slowly, thus allowing the egg to accept several sperm. An increase in
      intracellular Ca(2+) concentration induced by the fertilizing sperm is both
      necessary and sufficient for egg activation in polyspermy. Multiple small Ca(2+)
      waves induced by several fertilizing sperm result in a long-lasting Ca(2+) rise,
      which is a characteristic of polyspermic amphibian eggs. We introduced a novel
      soluble sperm factor for egg activation, sperm-specific citrate synthase, into
      polyspermic newt eggs to cause Ca(2+) waves. Citrate synthase may perform dual
      functions: as an enzyme in mitochondria and as a Ca(2+)-inducing factor in egg
      cytoplasm. We also discuss the close relationship between the mode of
      fertilization and the Ca(2+) rise at egg activation and consider changes in this
      process through evolution in vertebrates.

PMID- 22635305
TI  - Vitamin D metabolism, sex hormones, and male reproductive function.
AB  - The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and
      VD is now recognized as a versatile signaling molecule rather than being solely a
      regulator of bone health and calcium homeostasis. One of the recently identified
      target areas of VD is male reproductive function. The VD receptor (VDR) and the
      VD metabolizing enzyme expression studies documented the presence of this system
      in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both
      systemic and local VD metabolism may influence male reproductive function.
      However, it is still debated which cell is the main VD target in the testis and
      to what extent VD is important for sex hormone production and function of
      spermatozoa. This review summarizes descriptive studies on testicular VD
      metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the
      mammalian testes and discusses mechanistic and association studies conducted in
      animals and humans. The reviewed evidence suggests some effects of VD on estrogen
      and testosterone biosynthesis and implicates involvement of both systemic and
      local VD metabolism in the regulation of male fertility potential.

PMID- 22635324
TI  - High-precision flexible fabrication of tissue engineering scaffolds using
      distinct polymers.
AB  - Three-dimensional porous structures using biodegradable materials with excellent
      biocompatibility are critically important for tissue engineering applications. We
      present a multi-nozzle-based versatile deposition approach to flexibly construct
      porous tissue engineering scaffolds using distinct polymeric biomaterials such as
      thermoplastic and photo-crosslinkable polymers. We first describe the development
      of the deposition system and fabrication of scaffolds from two types of
      biodegradable polymers using this system. The thermoplastic sample is semi
      crystalline poly(epsilon-caprolactone) (PCL) that can be processed at a
      temperature higher than its melting point and solidifies at room temperature. The
      photo-crosslinkable one is polypropylene fumarate (PPF) that has to be dissolved
      in a reactive solvent as a resin for being cured into solid structures. Besides
      the direct fabrication of thermoplastic PCL scaffolds, we specifically develop a
      layer molding approach for the fabrication of crosslinkable polymers, which
      traditionally can only be fabricated by stereolithography. In this approach, a
      thermoplastic supporting material (paraffin wax) is first deposited to make a
      mold for each specific layer, and then PPF is deposited on demand to fill the
      mold and cured by the UV light. The supporting material can be removed to produce
      a porous scaffold of crosslinked PPF. Both PCL and crosslinked PPF scaffolds
      fabricated using the developed system have been characterized in terms of
      compressive mechanical properties, morphology, pore size and porosity. Mouse
      MC3T3-E1 pre-osteoblastic cell studies on the fabricated scaffolds have been
      performed to demonstrate their capability of supporting cell proliferation and
      ingrowth, aiming for bone tissue engineering applications.

PMID- 22635379
TI  - The genetics of dementia with Lewy bodies: what are we missing?
AB  - Dementia with Lewy bodies is a complex brain disorder and a key member of the
      Lewy body disease spectrum. Its genetic etiology is unclear, and information is
      scattered. However, the results of molecular genetic studies imply a genetic and
      mechanistic overlap with Alzheimer disease, Parkinson disease with dementia, and
      Parkinson disease. In this review, we provide a comprehensive overview of the
      current studies on dementia with Lewy bodies heritability, genetic etiology, and
      genetic heterogeneity. We conclude with a critical discussion of the missing
      heritability in dementia with Lewy bodies and encourage scientists to further
      explore the underlying mechanisms of this disease.

PMID- 22635387
TI  - Mid Staffordshire--an update.

PMID- 22635389
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1: Use of d dimer in excluding UEDVTs (upper extremity deep vein
      thrombosis).

PMID- 22635390
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2: Which fluid (colloids or crystalloids) is better in initial
      resuscitation of severe sepsis?

PMID- 22635391
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 3: Suxamethonium (succinylcholine) for RSI and intubation in head
      injury.

PMID- 22635392
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 4: Chest x-rays in bronchiolitis.

PMID- 22635402
TI  - Exchange interaction effects in electron spin resonance: Larmor theorem violation
      in narrow-gap quantum well heterostructures.
AB  - We report a theoretical study of the exchange interaction effects in the electron
      spin resonance (ESR) in n-type narrow-gap quantum well (QW) heterostructures.
      Using the Hartree-Fock approximation, based on the eight-band k?p Hamiltonian,
      the many-body correction to the ESR energy is found to be nonzero, providing
      theoretical evidence of Larmor theorem violation in symmetric narrow-gap QWs. We
      predict the exchange enhancement of the ESR g-factor and its divergence in low
      magnetic fields. The 'enhanced' ESR g-factor and quasiparticle g-factor, measured
      in magnetotransport, coincide at even-valued filling factors of the Landau levels
      in moderate and quantizing magnetic fields.

PMID- 22635416
TI  - Adherence to hepatitis B screening and prophylactic lamivudine for prevention of
      rituximab-associated hepatitis B reactivation.
AB  - PURPOSE: Treatment with rituximab can be associated with hepatitis B reactivation
      leading to fulminant hepatitis and sometimes fatal hepatitis. The manufacturer
      has recommended screening the high-risk patients and monitoring hepatitis B virus
      carriers during and several months after the therapy. Prophylaxis with lamivudine
      has been recommended to prevent reactivation in hepatitis B virus carriers
      receiving rituximab. An institutional guideline was developed and implemented.
      This study evaluated the adherence to these clinical guidelines of hepatitis B
      screening in patients receiving rituximab-based treatment, the use of lamivudine
      prophylaxis, and the prevalence of positive hepatitis B virus surface antigen in
      this patient population in southeast Michigan. METHODS: A retrospective chart
      review of patients begun on rituximab therapy from January 2009 through June 2010
      was conducted. RESULTS: Two hundred and eighty patients who received rituximab
      were identified. Approximately 70% of patients had hepatitis B virus surface
      antigen screening test prior to rituximab therapy. Antibody to hepatitis B virus
      core antigen was detected in 11.1% of patients, although the hepatitis B virus
      surface antigen positive rate was only 0.6%. One patient had hepatitis B virus
      reactivation despite lamivudine prophylaxis, but fully recovered after antiviral
      therapy was changed to tenofovir. CONCLUSION: The prevalence of hepatitis B virus
      surface antigen positivity is low in this study; however, antibody to hepatitis B
      virus core antigen positivity is high. Education to clinicians is warranted to
      increase awareness and further improve adherence to the clinical guidelines.

PMID- 22635403
TI  - Evidence for a cytoplasmic microprocessor of pri-miRNAs.
AB  - microRNAs (miRNAs) represent a class of noncoding RNAs that fine-tune gene
      expression through post-transcriptional silencing. While miRNA biogenesis occurs
      in a stepwise fashion, initiated by the nuclear microprocessor, rare noncanonical
      miRNAs have also been identified. Here we characterize the molecular components
      and unique attributes associated with the processing of virus-derived cytoplasmic
      primary miRNAs (c-pri-miRNAs). RNA in situ hybridization and inhibition of
      cellular division demonstrated a complete lack of nuclear involvement in c-pri
      miRNA cleavage while genetic studies revealed that maturation still relied on the
      canonical nuclear RNase III enzyme, Drosha. The involvement of Drosha was
      mediated by a dramatic relocalization to the cytoplasm following virus infection.
      Deep sequencing analyses revealed that the cytoplasmic localization of Drosha
      does not impact the endogenous miRNA landscape during infection, despite allowing
      for robust synthesis of virus-derived miRNAs in the cytoplasm. Taken together,
      this research describes a unique function for Drosha in the processing of highly
      structured cytoplasmic RNAs in the context of virus infection.

PMID- 22635404
TI  - The sperm-oocyte switch in the C. elegans hermaphrodite is controlled through
      steady-state levels of the fem-3 mRNA.
AB  - Post-transcriptional control regulates many aspects of germline development in
      the Caenorhabditis elegans hermaphrodite. This nematode switches from
      spermatogenesis to oogenesis and is, therefore, capable of self-fertilization.
      This sperm-oocyte switch requires 3' UTR-mediated repression of the fem-3 mRNA.
      Loss of fem-3 repression results in continuous spermatogenesis in hermaphrodites.
      Although several factors regulating fem-3 have been identified, little is known
      about the mechanisms that control fem-3. Here, we investigate the steady-state
      levels of the fem-3 transcript and the expression pattern of its protein product.
      We show that FEM-3 is exclusively present in germ cells that are committed to
      spermatogenesis. We found that in fem-3(gf)/+ heterozygotes, mutant fem-3 gain-of
      function transcripts are more abundant than their wild-type counterpart.
      Furthermore, we show that the penetrance of the fem-3(gf) allele correlates with
      inefficient FBF binding and extended poly(A) tail size of fem-3 mRNAs. Finally,
      we show that wild-type and gain-of-function mutated fem-3 mRNAs associate equally
      well with polyribosomes. We propose that the fem-3 mRNA is regulated through
      stabilization rather than through translatability.

PMID- 22635417
TI  - Successful clearance of cutaneous acyclovir-resistant, foscarnet-refractory
      herpes virus lesions with topical cidofovir in an allogeneic hematopoietic stem
      cell transplant patient.
AB  - Cidofovir is a deoxycytidine monophosphate analog with broad spectrum activity
      against various deoxyribonucleic acid viruses. Cidofovir is marketed as an
      injectable for intravenous use; however, there is a topical cidofovir formulation
      utilized for viral dermatologic infections. Here, we present a case of a
      successful clearance of a perianal acyclovir resistant and foscarnet refractory
      herpes simplex virus (HSV1) ulcer in a 34 year-old woman who had undergone
      allogeneic hematopoietic stem cell transplantation. After 1 week of therapy with
      cidofovir gel, the patient's ulcer was clinically improved, and the lesion was
      negative for herpes simplex virus transcripts by real-time polymerase chain
      reaction testing. The wound remained herpes simplex virus negative by real-time
      polymerase chain reaction on repeat testing 1 week later. Based on this and other
      reports in HIV/AIDS patients, we believe that cidofovir gel has utility in the
      management of cutaneous, acyclovir-resistant HSV infections.

PMID- 22635438
TI  - Evidence of the Fano resonance in a temperature dependent Raman study of
      CaCu3Ti4O12 and SrCu3Ti4O12.
AB  - Phononic excitations have been investigated using Raman scattering studies on
      CaCu(3)Ti(4)O(12) and SrCu(3)Ti(4)O(12) compounds as a function of temperature
      down to 10 K. Evidence of the Fano resonance effect is found in the A(g)(1) mode
      with an asymmetric phonon line shape that occurs because of composite electron
      phonon scattering due to the onset of metallic fractions in the system. The
      evolution of the Fano line shape with temperature affirms the existence of
      nanoscale phase separation and the prominence of orbitally disrupted metallic
      regions above 100 K. Anomalies in the evolution of the line width of the A(g)(1)
      Raman mode with temperature are observed around 100 K where these compounds show
      an orbital order/disorder transition. These anomalies manifest mutual coupling of
      orbital degrees of freedom to lattice degrees of freedom.

PMID- 22635521
TI  - Vibrational spectrum of solid picene (C22H14).
AB  - Recently, Mitsuhashi et al observed superconductivity with a transition
      temperature up to 18 K in potassium doped picene (C(22)H(14)), a polycyclic
      aromatic hydrocarbon compound (Mitsuhashi et al 2010 Nature 464 76). Theoretical
      analysis indicates the importance of electron-phonon coupling in the
      superconducting mechanisms of these systems, with different emphasis on inter-
      and intra-molecular vibrations, depending on the approximations used. Here we
      present a combined experimental and ab initio study of the Raman and infrared
      spectrum of undoped solid picene, which allows us to unambiguously assign the
      vibrational modes. This combined study enables the identification of the modes
      which couple strongly to electrons and hence can play an important role in the
      superconducting properties of the doped samples.

PMID- 22635523
TI  - Association of cerebral microbleeds in acute ischemic stroke with high serum
      levels of vascular endothelial growth factor.
AB  - OBJECTIVE: To determine whether vascular endothelial growth factor (VEGF) levels
      are associated with the presence of cerebral microbleeds (CMBs) in patients after
      acute ischemic stroke. DESIGN: A cross-sectional study that used blood samples
      obtained within 24 hours of symptom onset from patients who experienced acute
      stroke to measure VEGF levels by enzyme immunoassay. A validated CMB rating scale
      was used to analyze acutely acquired magnetic resonance images, with the rater
      blind to clinical details and VEGF levels. SETTING: Accident and Emergency
      Department at University College Hospital, London, England. PATIENTS: Twenty
      patients who experienced acute ischemic stroke. MAIN OUTCOME MEASURES: Presence
      of CMBs and serum level of VEGF. RESULTS: Five of the 20 patients with acute
      ischemic stroke (25%) had CMBs. The median VEGF level in the CMB group was
      significantly higher than that in the group without CMBs (P = .003). CONCLUSION:
      An increase in vascular permeability secondary to a raised VEGF level may have a
      role in the genesis of CMBs in patients with acute ischemic stroke.

PMID- 22635524
TI  - Intensification of antibiotic use within acute care hospitals in the Netherlands.
AB  - OBJECTIVES: To report and analyse trends in antibiotic use in Dutch university
      hospitals, large teaching hospitals and general hospitals over the period 2003 to
      2009. METHODS: Data on the use of antibiotics and hospital resource indicators
      were obtained by distributing a questionnaire to all Dutch hospital pharmacies.
      Antibiotic use was expressed as the number of defined daily doses (DDDs) per 100
      patient-days, per 100 admissions and per 1000 inhabitants per day. The latter was
      achieved by extrapolating sample data by means of imputation and up-scaling.
      RESULTS: From 2003 to 2009, the mean length of hospital stay decreased from 6.27
      to 4.50 days (-28%). Total systemic antibiotic use significantly increased from
      52.3 to 69.8 DDDs per 100 patient-days (P < 0.001). Despite the overall constant
      use when expressed in DDDs per 100 admissions, we found a significant increase in
      the total use of piperacillin/tazobactam, cefazolin, ceftriaxone, meropenem,
      azithromycin, gentamicin, ciprofloxacin and vancomycin. Mean total systemic use
      expressed in DDDs per 1000 inhabitants per day gradually increased by 38% from
      0.73 in 2003 to 1.01 in 2009. CONCLUSIONS: Total hospital antibiotic consumption
      is still low in the Netherlands compared with other European countries. Also,
      between 2003 and 2009 the use of antibiotics in individual hospitalized patients
      remained stable. However, since they remained in the hospital for a shorter
      period of time, the number of DDDs per 100 patient-days increased. This results
      in an intensification of antibiotic treatment per hospital bed, leading to a
      possible increase in selection pressure towards resistance. This may create a
      problem for future patients. To limit the emergence and transmission of
      antimicrobial-resistant bacteria, effective antibiotic stewardship is essential.

PMID- 22635526
TI  - In vitro and in vivo effects of echinocandins against Candida parapsilosis sensu
      stricto, Candida orthopsilosis and Candida metapsilosis.
AB  - OBJECTIVES: The aim of the present study was to compare, in vitro and in vivo,
      the effects of caspofungin, micafungin and anidulafungin against Candida
      parapsilosis complex isolates. METHODS: In vitro activities of all three
      echinocandins were assessed against C. parapsilosis sensu stricto (n = 4),
      Candida orthopsilosis (n = 4) and Candida metapsilosis (n = 3) using broth
      microdilution susceptibility testing, minimum fungicidal concentration
      determination and a killing-curve assay, in the absence and in the presence of
      50% human serum. Then, the activities of all drugs were investigated in an
      immunocompromised murine model of systemic candidiasis. Animals were infected
      with six isolates (two for each species) and treated with the echinocandins
      administered at 0.25, 1, 5 and 10 mg/kg/day for six consecutive days. Fungal
      burdens were assessed in kidney tissues on day 7 post-infection. RESULTS:
      Geometric mean MICs of caspofungin, micafungin and anidulafungin for C.
      parapsilosis sensu lato were, respectively, 0.09, 0.14 and 0.20 mg/L without
      serum, and 0.70, 3.92 and 5.84 mg/L with serum. The fungicidal activity of all
      three echinocandins was variable; however, the addition of serum reduced the
      fungicidal effects against these species. In vivo studies showed that caspofungin
      at 5 and 10 mg/kg/day significantly decreased the kidney burdens with respect to
      the controls for all isolates, while micafungin was active at 5 and/or 10
      mg/kg/day only against C. metapsilosis. CONCLUSIONS: Our susceptibility testing
      showed that caspofungin was the most active echinocandin against all three
      species. Also, caspofungin resulted in significant therapeutic effects for
      treatments of experimental systemic infections due to the three species, while
      micafungin was effective only against C. metapsilosis.

PMID- 22635603
TI  - Coulomb problem on single- and double-wall cylinders.
AB  - In this paper we calculate the energies of ground and excited states of two
      opposite charge carriers confined on a single- or double-wall cylindrical
      surface. A nontrivial dependence of excited state energies on cylinder radius
      value (for the case of a single-wall cylinder) is found, and the explanation of
      this behavior is based on symmetry properties of the corresponding wavefunctions.
      The crossover from a one-dimensional problem to a two-dimensional one with
      increase of the radius value is discussed in detail. For the double-wall
      cylinder, we obtain and analyze the dependence of ground state energy on
      interwall distance and ratio between particle masses.

PMID- 22635525
TI  - A new in vivo model to test anti-tuberculosis drugs using fluorescence imaging.
AB  - OBJECTIVES: The current method for testing new drugs against tuberculosis in vivo
      is the enumeration of bacteria in organs by cfu assay. Owing to the slow growth
      rate of Mycobacterium tuberculosis (Mtb), these assays can take months to
      complete. Our aim was to develop a more efficient, fluorescence-based imaging
      assay to test new antibiotics in a mouse model using Mtb reporter strains.
      METHODS: A commercial IVIS Kinetic(r) system and a custom-built laser scanning
      system with fluorescence molecular tomography (FMT) capability were used to
      detect fluorescent Mtb in living mice and lungs ex vivo. The resulting images
      were analysed and the fluorescence was correlated with data from cfu assays.
      RESULTS: We have shown that fluorescent Mtb can be visualized in the lungs of
      living mice at a detection limit of ~8 * 107 cfu/lung, whilst in lungs ex vivo a
      detection limit of ~2 * 105 cfu/lung was found. These numbers were comparable
      between the two imaging systems. Ex vivo lung fluorescence correlated to numbers
      of bacteria in tissue, and the effect of treatment of mice with the antibiotic
      moxifloxacin could be visualized and quantified after only 9 days through
      fluorescence measurements, and was confirmed by cfu assays. CONCLUSIONS: We have
      developed a new and efficient method for anti-tuberculosis drug testing in vivo,
      based on fluorescent Mtb reporter strains. Using this method instead of, or
      together with, cfu assays will reduce the time required to assess the preclinical
      efficacy of new drugs in animal models and enhance the progress of these
      candidates into clinical trials against human tuberculosis.

PMID- 22635605
TI  - BATMAN--an R package for the automated quantification of metabolites from nuclear
      magnetic resonance spectra using a Bayesian model.
AB  - MOTIVATION: Nuclear Magnetic Resonance (NMR) spectra are widely used in
      metabolomics to obtain metabolite profiles in complex biological mixtures. Common
      methods used to assign and estimate concentrations of metabolites involve either
      an expert manual peak fitting or extra pre-processing steps, such as peak
      alignment and binning. Peak fitting is very time consuming and is subject to
      human error. Conversely, alignment and binning can introduce artefacts and limit
      immediate biological interpretation of models. RESULTS: We present the Bayesian
      automated metabolite analyser for NMR spectra (BATMAN), an R package that
      deconvolutes peaks from one-dimensional NMR spectra, automatically assigns them
      to specific metabolites from a target list and obtains concentration estimates.
      The Bayesian model incorporates information on characteristic peak patterns of
      metabolites and is able to account for shifts in the position of peaks commonly
      seen in NMR spectra of biological samples. It applies a Markov chain Monte Carlo
      algorithm to sample from a joint posterior distribution of the model parameters
      and obtains concentration estimates with reduced error compared with conventional
      numerical integration and comparable to manual deconvolution by experienced
      spectroscopists. AVAILABILITY AND IMPLEMENTATION:
      http://www1.imperial.ac.uk/medicine/people/t.ebbels/ CONTACT:
      t.ebbels@imperial.ac.uk.

PMID- 22635606
TI  - Gowinda: unbiased analysis of gene set enrichment for genome-wide association
      studies.
AB  - SUMMARY: An analysis of gene set [e.g. Gene Ontology (GO)] enrichment assumes
      that all genes are sampled independently from each other with the same
      probability. These assumptions are violated in genome-wide association (GWA)
      studies since (i) longer genes typically have more single-nucleotide
      polymorphisms resulting in a higher probability of being sampled and (ii)
      overlapping genes are sampled in clusters. Herein, we introduce Gowinda, a
      software specifically designed to test for enrichment of gene sets in GWA
      studies. We show that GO tests on GWA data could result in a substantial number
      of false-positive GO terms. Permutation tests implemented in Gowinda eliminate
      these biases, but maintain sufficient power to detect enrichment of GO terms.
      Since sufficient resolution for large datasets requires millions of permutations,
      we use multi-threading to keep computation times reasonable. AVAILABILITY AND
      IMPLEMENTATION: Gowinda is implemented in Java (v1.6) and freely available on
      http://code.google.com/p/gowinda/ CONTACT: christian.schloetterer@vetmeduni.ac.at
      SUPPLEMENTARY INFORMATION: Manual: http://code.google.com/p/gowinda/wiki/Manual.
      Test data and tutorial: http://code.google.com/p/gowinda/wiki/Tutorial.
      VALIDATION: http://code.google.com/p/gowinda/wiki/VALIDATION.

PMID- 22635607
TI  - A tutorial on fatty acid biology.
AB  - Fatty acids are an extraordinarily diverse set of molecules that serve as sources
      of fuel, key components of cell structure, and parent molecules for bioactive
      second messengers. The metabolism of fatty acids is part of a delicate
      homeostasis that is fundamental to normal functioning and the response to
      pathophysiologic insult. The growing body of evidence on nutrition demonstrates
      that we truly "are what we eat," and the fatty acid content of our diets has far
      reaching physiologic implications, many of which we are only beginning to
      understand. As the gap between basic science and patient care becomes
      increasingly narrow, clinicians should have a working knowledge of fatty acid
      biology. This tutorial provides an overview of fatty acid biology with the goal
      of increasing comfort in discussing how these heterogeneous molecules are
      classified and metabolized, in addition to how fatty acid content influences
      basic cellular processes.

PMID- 22635608
TI  - Postmortem levetiracetam (Keppra(r)) data from North Carolina.
AB  - Levetiracetam (Keppra(r)) is one of the newer anticonvulsant drugs used to treat
      seizures. Since 2003, the North Carolina Office of the Chief Medical Examiner
      Toxicology Laboratory has collected quantitative levetiracetam data in samples
      for 56 postmortem cases. The data presented herein will provide the forensic
      community with concentrations to assist in the interpretation of levetiracetam in
      postmortem blood. Decedents were divided into two groups according to manner of
      death as determined by the medical examiner for the purposes of studying
      levetiracetam concentrations. There were equal numbers of natural (N = 28) and
      non-natural deaths (N = 28). These data were subsequently divided into subgroups
      for further study to explore the therapeutic range of levetiracetam and how it
      relates to postmortem data. The cases not certified as natural were investigated
      to study levetiracetam concentrations in cases where it was determined to
      contribute to the cause of death (attributed) and those where it was not
      (unattributed). Until now, the literature has only reported levetiracetam
      overdoses in which the individuals have recovered with respiratory support.
      Discussed are two suicidal drug deaths from 2010 that are noted to have elevated
      levels of levetiracetam, 190 and 35 mg/L. Also included in the complete data set
      are postmortem concentrations for five patients under the age of 10 with
      levetiracetam ranging from 1.4 to 50 mg/L. This paper will also address the
      adverse effects of the drug and explore its potential risk for suicide.

PMID- 22635677
TI  - Spinal motor and sensory neurons are androgen targets in an acrobatic bird.
AB  - Sex steroids affect the motivation to court mates, but less is known about how
      they influence motor movements associated with courtship behavior. Steroidal
      control of motor function may be especially important for species in which
      courtship requires superior strength, stamina, and neuromuscular coordination.
      Here we use the golden-collared manakin (Manacus vitellinus) to examine whether
      the neuromuscular circuitry that controls motoric aspects of courtship activity
      is sensitive to androgens. Males of this tropical species attract mates by
      rapidly jumping among branches in a courtship arena and using their wings to
      produce loud wing snaps. Testosterone activates this display via the androgen
      receptor (AR), and past work reveals that manakins injected with radio-labeled T
      ((3)H-T) accumulate radioactivity in the spinal cord. Thus, we used quantitative
      PCR to measure AR, estrogen receptor-alpha (ER-alpha) subtype, and aromatase
      (AROM) mRNA in spinal cords of male and female manakins and zebra finches.
      Expression of AR, but not ER-alpha or aromatase, was higher throughout the
      manakin spinal cord compared with the zebra finch. Next, we tested whether AR
      expressing skeletal muscles are innervated by motor and sensory neurons that also
      express AR. To do this, we backfilled spinal neurons by injecting fluorescent
      tracers into select AR-sensitive wing and leg muscles of wild caught male and
      female manakins. We then removed these spinal cords and measured AR expression
      with in situ hybridization. Both sexes showed abundant AR mRNA in the cervical
      and lumbosacral spinal enlargements as well as in dorsal root ganglia attached to
      these enlargements. Together our findings suggest that androgens act widely on
      peripheral motor and sensory circuits in golden-collared manakins to influence
      wing snapping displays.

PMID- 22635678
TI  - Progesterone receptors: a key for neuroprotection in experimental stroke.
AB  - Progesterone receptors (PR) are expressed throughout the brain. However, their
      functional significance remains understudied. Here we report a novel role of PR
      as crucial mediators of neuroprotection using a model of transient middle
      cerebral artery occlusion and PR knockout mice. Six hours after ischemia, we
      observed a rapid increase in progesterone and 5alpha-dihydroprogesterone, the
      endogenous PR ligands, a process that may be a part of the natural
      neuroprotective mechanisms. PR deficiency, and even haploinsufficiency, increases
      the susceptibility of the brain to stroke damage. Within a time window of 24 h,
      PR-dependent signaling of endogenous brain progesterone limits the extent of
      tissue damage and the impairment of motor functions. Longer-term improvement
      requires additional treatment with exogenous progesterone and is also PR
      dependent. The potent and selective PR agonist Nestorone is also effective. In
      contrast to progesterone, levels of the neurosteroid allopregnanolone, which
      modulates gamma-aminobutyric acid type A receptors, did not increase after
      stroke, but its administration protected both wild-type and PR-deficient mice
      against ischemic damage. These results show that 1) PR are linked to signaling
      pathways that influence susceptibility to stroke, and 2) PR are direct key
      targets for both endogenous neuroprotection and for therapeutic strategies after
      stroke, and they suggest a novel indication for synthetic progestins already
      validated for contraception. Although allopregnanolone may not be an endogenous
      neuroprotective agent, its administration protects the brain against ischemic
      damage by signaling mechanisms not involving PR. Collectively, our data clarify
      the relative roles of PR and allopregnanolone in neuroprotection after stroke.

PMID- 22635679
TI  - G protein-coupled receptor 30 mediates estrogen-induced proliferation of
      primordial germ cells via EGFR/Akt/beta-catenin signaling pathway.
AB  - In vertebrates, estrogens are required for the normal development and function of
      postnatal gonads. However, it remains unclear whether estrogens are able to
      modulate development of the fetal germ cells. Here, we show that, unexpectedly,
      chicken primordial germ cells (PGC) lacking estrogen receptor alpha/beta still
      proliferate in response to 17beta-estradiol (E(2)). This is due to the capacity
      of G protein-coupled receptor 30 (GPR30), existing on PGC, to directly bind E(2).
      Knockdown experiments suggest that GPR30 is required for E(2)-stimulated PGC
      proliferation. Furthermore, this estrogen-induced activation of GPR30 is revealed
      to occur through the Gbetagamma-subunit protein-dependent and through the matrix
      metalloproteinase-dependent transactivation of the epidermal growth factor
      receptor. Epidermal growth factor receptor activation results in a series of
      intracellular events, including activation of the phosphatidylinositol 3
      kinase/serine-threonine kinase/beta-catenin pathway, which are followed by the
      induction of c-fos, c-myc, cyclin D1/E, and B-cell lymphoma 2 expression, and the
      inhibition of B-cell lymphoma 2-associated X protein expression and caspase3/9
      activity. This eventually leads to decreased apoptosis and increased PGC
      proliferation. Collectively, these findings offer novel insights into the dynamic
      mechanism of estrogen action on PGC proliferation and suggest that E(2)/GPR30
      signaling might play an important role in regulating fetal germ cell development,
      particularly at the stage before sexual differentiation.

PMID- 22635680
TI  - Genomic characterization of human and rat prolactinomas.
AB  - Although prolactinomas can be effectively treated with dopamine agonists, about
      20% of patients develop dopamine resistance or tumor recurrence after surgery,
      indicating a need for better understanding of underlying disease mechanisms.
      Although estrogen-induced rat prolactinomas have been widely used to investigate
      the development of this tumor, the extent that the model recapitulates features
      of human prolactinomas is unclear. To prioritize candidate genes and gene sets
      regulating human and rat prolactinomas, microarray results derived from human
      prolactinomas and pituitaries of estrogen-treated ACI rats were integrated and
      analyzed. A total of 4545 differentially expressed pituitary genes were
      identified in estrogen-treated ACI rats [false discovery rate (FDR) < 0.01]. By
      comparing pituitary microarray results derived from estrogen-treated Brown Norway
      rats (a strain not sensitive to estrogen), 4073 genes were shown specific to
      estrogen-treated ACI rats. Human prolactinomas exhibited 1177 differentially
      expressed genes (FDR < 0.05). Combining microarray data derived from human
      prolactinoma and pituitaries of estrogen-treated ACI rat, 145 concordantly
      expressed genes, including E2F1, Myc, Igf1, and CEBPD, were identified. Gene set
      enrichment analysis revealed that 278 curated pathways and 59 gene sets of
      transcription factors were enriched (FDR < 25%) in estrogen-treated ACI rats,
      suggesting a critical role for Myc, E2F1, CEBPD, and Sp1 in this rat
      prolactinoma. Similarly increased Myc, E2F1, and Sp1 expression was validated
      using real-time PCR and Western blot in estrogen-treated Fischer rat pituitary
      glands. In summary, characterization of individual genes and gene sets in human
      and in estrogen-induced rat prolactinomas validates the model and provides
      insights into genomic changes associated with this commonly encountered pituitary
      tumor.

PMID- 22635821
TI  - "It's like pay or don't have it and now I'm doing without": the voice of
      transitional uninsured former foster youth.
AB  - Twenty-four thousand American youth lose Medicaid entitlements after discharge
      from foster care annually. The circumstance of being uninsured is a formidable
      barrier to health care that leaves the youth vulnerable to unmet health care
      needs. Given that foster youth often develop physical and/or mental health
      problems as a result of abuse or neglect, continuous access to health care is
      especially important. This descriptive phenomenology study explores the lived
      experience of transitional uninsured former foster youth. Nine uninsured former
      foster youth were recruited from a nonprofit community organization in an urban
      county and interviewed using semistructured interviews. Four themes identified
      from the analysis were (a) "Surviving the real world": emancipation without
      essential documentation; (b) "It's not always going to be fine": managing mental
      and physical health without health care insurance; (c) "Roadblocks": barriers to
      securing health care insurance; and (d) "Just not knowing": Medicaid eligible
      albeit without health care insurance.

PMID- 22635822
TI  - Filaggrin mutations are not associated with chronic allergic
      keratoconjunctivitis.

PMID- 22635919
TI  - A lysine-rich region within fungal BAG domain-containing proteins mediates a
      novel association with ribosomes.
AB  - Heat shock protein 70 (Hsp70) is a highly conserved molecular chaperone that
      assists in the folding of nascent chains and the repair of unfolded proteins
      through iterative cycles of ATP binding, hydrolysis, and nucleotide exchange
      tightly coupled to polypeptide binding and release. Cochaperones, including
      nucleotide exchange factors (NEFs), modulate the rate of ADP/ATP exchange and
      serve to recruit Hsp70 to distinct processes or locations. Among three nonrelated
      cytosolic NEFs in Saccharomyces cerevisiae, the Bag-1 homolog SNL1 is unique in
      being tethered to the endoplasmic reticulum (ER) membrane. We demonstrate here a
      novel physical association between Snl1 and the intact ribosome. This interaction
      is both independent of and concurrent with binding to Hsp70 and is not dependent
      on membrane localization. The ribosome binding site is identified as a short
      lysine-rich motif within the amino terminus of the Snl1 BAG domain distinct from
      the Hsp70 interaction region. Additionally, we demonstrate a ribosome association
      with the Candida albicans Snl1 homolog and localize this putative NEF to a
      perinuclear/ER membrane, suggesting functional conservation in fungal BAG domain
      containing proteins. We therefore propose that the Snl1 family of NEFs serves a
      previously unknown role in fungal protein biogenesis based on the coincident
      recruitment of ribosomes and Hsp70 to the ER membrane.

PMID- 22635920
TI  - The heat-induced molecular disaggregase Hsp104 of Candida albicans plays a role
      in biofilm formation and pathogenicity in a worm infection model.
AB  - The consequences of deprivation of the molecular chaperone Hsp104 in the fungal
      pathogen Candida albicans were investigated. Mutants lacking HSP104 became
      hypersusceptible to lethally high temperatures, similarly to the corresponding
      mutants of Saccharomyces cerevisiae, whereas normal susceptibility was restored
      upon reintroduction of the gene. By use of a strain whose only copy of HSP104 is
      an ectopic gene under the control of a tetracycline-regulated promoter,
      expression of Hsp104 prior to the administration of heat shock could be
      demonstrated to be sufficient to confer protection from the subsequent
      temperature increase. This result points to a key role for Hsp104 in
      orchestrating the cell response to elevated temperatures. Despite their not
      showing evident growth or morphological defects, biofilm formation by cells
      lacking HSP104 proved to be defective in two established in vitro models that use
      polystyrene and polyurethane as the substrates. Biofilms formed by the wild-type
      and HSP104-reconstituted strains showed patterns of intertwined hyphae in the
      extracellular matrix. In contrast, biofilm formed by the hsp104Delta/hsp104Delta
      mutant showed structural defects and appeared patchy and loose. Decreased
      virulence of the hsp104Delta/hsp104Delta mutant was observed in the
      Caenorhabditis elegans infection model, in which high in vivo temperature does
      not play a role. In agreement with the view that stress responses in fungal
      pathogens may have evolved to provide niche-specific adaptation to environmental
      conditions, these results provide an indication of a temperature-independent role
      for Hsp104 in support of Candida albicans virulence, in addition to its key role
      in governing thermotolerance.

PMID- 22635921
TI  - Protein kinase A regulatory subunit isoforms regulate growth and differentiation
      in Mucor circinelloides: essential role of PKAR4.
AB  - The protein kinase A (PKA) signaling pathway plays a role in regulating growth
      and differentiation in the dimorphic fungus Mucor circinelloides. PKA holoenzyme
      is comprised of two catalytic (C) and two regulatory (R) subunits. In M.
      circinelloides, four genes encode the PKAR1, PKAR2, PKAR3, and PKAR4 isoforms of
      R subunits. We have constructed null mutants and demonstrate that each isoform
      has a different role in growth and differentiation. The most striking finding is
      that pkaR4 is an essential gene, because only heterokaryons were obtained in
      knockout experiments. Heterokaryons with low levels of wild-type nuclei showed an
      impediment in the emission of the germ tube, suggesting a pivotal role of this
      gene in germ tube emergence. The remaining null strains showed different
      alterations in germ tube emergence, sporulation, and volume of the mother cell.
      The pkaR2 null mutant showed an accelerated germ tube emission and was the only
      mutant that germinated under anaerobic conditions when glycine was used as a
      nitrogen source, suggesting that pkaR2 participates in germ tube emergence by
      repressing it. From the measurement of the mRNA and protein levels of each
      isoform in the wild-type and knockout strains, it can be concluded that the
      expression of each subunit has its own mechanism of differential regulation. The
      PKAR1 and PKAR2 isoforms are posttranslationally modified by ubiquitylation,
      suggesting another regulation point in the specificity of the signal
      transduction. The results indicate that each R isoform has a different role in M.
      circinelloides physiology, controlling the dimorphism and contributing to the
      specificity of cyclic AMP (cAMP)-PKA pathway.

PMID- 22635965
TI  - Pre-filling of the extracorporeal circuit with autologous blood is safe, but not
      effective in optimizing biocompatibility in high-risk patients.
AB  - OBJECTIVES: Haemodilution resulting from crystalloid priming of the
      cardiopulmonary bypass circuit represents a major risk factor for blood
      transfusions in high-risk cardiac surgery patients. We designed this study to
      evaluate the effects of antegrade autologous priming (AAP) on reducing
      perioperative blood transfusion and markers of the inflammatory response in older
      patients (>75 years). METHODS: Seventy-two patients undergoing first-time
      coronary bypass and/or aortic valve replacement were prospectively randomised to
      a cardiopulmonary bypass (CPB) with or without AAP. AAP was performed by adding
      the patient's own blood to the prime solution (mean 280 ml). Perfusion and
      anaesthetic techniques were as usual. The haematocrit was maintained at a minimum
      of 21% during CPB. Patients were well matched for all preoperative variables,
      including established transfusion risk factors. The primary endpoint was the
      requirement of red cell transfusion. The surrogate endpoints were renal function,
      inflammatory response and ischaemic parameters. Blood samples were drawn pre- and
      intraoperatively and at intervals of 6 hours till POD 6. RESULTS: Current
      analysis shows no differences in patients receiving homologous packed red cell
      transfusions. Also, markers of the inflammatory response (IL6, IL8), renal
      function (cystatin C, creatinine) and myocardial ischaemia (troponin T, CK-MB)
      were comparable in both groups (p>0.05). Clinical outcomes were similar with
      respect to pulmonary, renal and hepatic function, length of ICU stay and hospital
      stay. CONCLUSION: These data suggest that antegrade autologous priming is a safe
      procedure, but an ineffective way for improving biocompatibility and reducing the
      need for blood transfusion in older patients.

PMID- 22635922
TI  - Role of Fig1, a component of the low-affinity calcium uptake system, in growth
      and sexual development of filamentous fungi.
AB  - The function of Fig1, a transmembrane protein of the low-affinity calcium uptake
      system (LACS) in fungi, was examined for its role in the growth and development
      of the plant pathogen Fusarium graminearum. The Deltafig1 mutants failed to
      produce mature perithecia, and sexual development was halted prior to the
      formation of perithecium initials. The loss of Fig1 function also resulted in a
      reduced vegetative growth rate. Macroconidium production was reduced 70-fold in
      the Deltafig1 mutants compared to the wild type. The function of the high
      affinity calcium uptake system (HACS), comprised of the Ca(2+) channels Mid1 and
      Cch1, was previously characterized for F. graminearum. To better understand the
      roles of the LACS and the HACS, Deltafig1 Deltamid1, Deltafig1 Deltacch1, and
      Deltafig1 Deltamid1 Deltacch1 double and triple mutants were generated, and the
      phenotypes of these mutants were more severe than those of the Deltafig1 mutants.
      Pathogenicity on wheat was unaffected for the Deltafig1 mutants, but the
      Deltafig1 Deltamid1, Deltafig1 Deltacch1, and Deltafig1 Deltamid1 Deltacch1
      mutants, lacking both LACS and HACS functions, had reduced pathogenicity.
      Additionally, Deltafig1 mutants of Neurospora crassa were examined and did not
      affect filamentous growth or female fertility in a Deltafig1 mating type A
      strain, but the Deltafig1 mating type a strain failed to produce fertile fruiting
      bodies. These results are the first report of Fig1 function in filamentous
      ascomycetes and expand its role to include complex fruiting body and ascus
      development.

PMID- 22635987
TI  - The bacterial surface layer provides protection against antimicrobial peptides.
AB  - This report describes a previously unrecognized role for bacterial surface layers
      as barriers that confer protection against antimicrobial peptides. As
      antimicrobial peptides exist in natural environments, S-layers may provide a
      bacterial survival mechanism that has been selected for through evolution.

PMID- 22635988
TI  - A conserved two-component signal transduction system controls the response to
      phosphate starvation in Bifidobacterium breve UCC2003.
AB  - This work reports on the identification and molecular characterization of the two
      component regulatory system (2CRS) PhoRP, which controls the response to
      inorganic phosphate (P(i)) starvation in Bifidobacterium breve UCC2003. The
      response regulator PhoP was shown to bind to the promoter region of pstSCAB,
      specifying a predicted P(i) transporter system, as well as that of phoU, which
      encodes a putative P(i)-responsive regulatory protein. This interaction is
      assumed to cause transcriptional modulation under conditions of P(i) limitation.
      Our data suggest that the phoRP genes are subject to positive autoregulation and,
      together with pstSCAB and presumably phoU, represent the complete regulon
      controlled by the phoRP-encoded 2CRS in B. breve UCC2003. Determination of the
      minimal PhoP binding region combined with bioinformatic analysis revealed the
      probable recognition sequence of PhoP, designated here as the PHO box, which
      together with phoRP is conserved among many high-GC-content Gram-positive
      bacteria. The importance of the phoRP 2CRS in the response of B. breve to P(i)
      starvation conditions was confirmed by analysis of a B. breve phoP insertion
      mutant which exhibited decreased growth under phosphate-limiting conditions
      compared to its parent strain UCC2003.

PMID- 22635989
TI  - Influence of artisan bakery- or laboratory-propagated sourdoughs on the diversity
      of lactic acid bacterium and yeast microbiotas.
AB  - Seven mature type I sourdoughs were comparatively back-slopped (80 days) at
      artisan bakery and laboratory levels under constant technology parameters. The
      cell density of presumptive lactic acid bacteria and related biochemical features
      were not affected by the environment of propagation. On the contrary, the number
      of yeasts markedly decreased from artisan bakery to laboratory propagation.
      During late laboratory propagation, denaturing gradient gel electrophoresis
      (DGGE) showed that the DNA band corresponding to Saccharomyces cerevisiae was no
      longer detectable in several sourdoughs. Twelve species of lactic acid bacteria
      were variously identified through a culture-dependent approach. All sourdoughs
      harbored a certain number of species and strains, which were dominant throughout
      time and, in several cases, varied depending on the environment of propagation.
      As shown by statistical permutation analysis, the lactic acid bacterium
      populations differed among sourdoughs propagated at artisan bakery and laboratory
      levels. Lactobacillus plantarum, Lactobacillus sakei, and Weissella cibaria
      dominated in only some sourdoughs back-slopped at artisan bakeries, and
      Leuconostoc citreum seemed to be more persistent under laboratory conditions.
      Strains of Lactobacillus sanfranciscensis were indifferently found in some
      sourdoughs. Together with the other stable species and strains, other lactic acid
      bacteria temporarily contaminated the sourdoughs and largely differed between
      artisan bakery and laboratory levels. The environment of propagation has an
      undoubted influence on the composition of sourdough yeast and lactic acid
      bacterium microbiotas.

PMID- 22635990
TI  - High-pressure inactivation of human norovirus virus-like particles provides
      evidence that the capsid of human norovirus is highly pressure resistant.
AB  - Human norovirus (NoV) is the leading cause of nonbacterial acute gastroenteritis
      epidemics worldwide. High-pressure processing (HPP) has been considered a
      promising nonthermal processing technology to inactivate food- and waterborne
      viral pathogens. Due to the lack of an effective cell culture method for human
      NoV, the effectiveness of HPP in inactivating human NoV remains poorly
      understood. In this study, we evaluated the effectiveness of HPP in disrupting
      the capsid of human NoV based on the structural and functional integrity of virus
      like particles (VLPs) and histo-blood group antigen (HBGA) receptor binding
      assays. We found that pressurization at 500 to 600 MPa for 2 min, a pressure
      level that completely inactivates murine norovirus and feline calicivirus, was
      not sufficient to disrupt the structure and function of human NoV VLPs, even with
      a holding time of 60 min. Degradation of VLPs increased commensurate with
      increasing pressure levels more than increasing time. The times required for
      complete disruption of human NoV VLPs at 700, 800, and 900 MPa were 45, 15, and 2
      min, respectively. Human NoV VLPs were more resistant to HPP in their ability to
      bind type A than type B and O HBGAs. Additionally, the 23-nm VLPs appeared to be
      much more stable than the 38-nm VLPs. Taken together, our results demonstrated
      that the human NoV capsid is highly resistant to HPP. While human NoV VLPs may
      not be fully representative of viable human NoV, destruction of the VLP capsid is
      highly suggestive of a typical response for viable human NoV.

PMID- 22635991
TI  - Ciliates expel environmental Legionella-laden pellets to stockpile food.
AB  - When Tetrahymena ciliates are cultured with Legionella pneumophila, the ciliates
      expel bacteria packaged in free spherical pellets. Why the ciliates expel these
      pellets remains unclear. Hence, we determined the optimal conditions for pellet
      expulsion and assessed whether pellet expulsion contributes to the maintenance of
      growth and the survival of ciliates. When incubated with environmental L.
      pneumophila, the ciliates expelled the pellets maximally at 2 days after
      infection. Heat-killed bacteria failed to produce pellets from ciliates, and
      there was no obvious difference in pellet production among the ciliates or
      bacterial strains. Morphological studies assessing lipid accumulation showed that
      pellets contained tightly packed bacteria with rapid lipid accumulation and were
      composed of the layers of membranes; bacterial culturability in the pellets
      rapidly decreased, in contrast to what was seen in ciliate-free culture, although
      the bacteria maintained membrane integrity in the pellets. Furthermore, ciliates
      newly cultured with pellets were maintained and grew vigorously compared with
      those without pellets. In contrast, a human L. pneumophila isolate killed
      ciliates 7 days postinfection in a Dot/Icm-dependent manner, and pellets
      harboring this strain did not support ciliate growth. Also, pellets harboring the
      human isolate were resuscitated by coculturing with amoebae, depending on Dot/Icm
      expression. Thus, while ciliates expel pellet-packaged environmental L.
      pneumophila for stockpiling food, the pellets packaging the human isolate are
      harmful to ciliate survival, which may be of clinical significance.

PMID- 22635993
TI  - O-Demethylation and successive oxidative dechlorination of methoxychlor by
      Bradyrhizobium sp. strain 17-4, isolated from river sediment.
AB  - O-Demethylation of insecticide methoxychlor is well known as a phase I metabolic
      reaction in various eukaryotic organisms. Regarding prokaryotic organisms,
      however, no individual species involved in such reaction have been specified and
      characterized so far. Here we successfully isolated a bacterium that mediates
      oxidative transformation of methoxychlor, including O-demethylation and
      dechlorination, from river sediment. The isolate was found to be closely related
      to Bradyrhizobium elkanii at the 16S rRNA gene sequence level (100% identical).
      However, based on some differences in the physiological properties of this
      bacterium, we determined that it was actually a different species, Bradyrhizobium
      sp. strain 17-4. The isolate mediated O-demethylation of methoxychlor to yield a
      monophenolic derivative [Mono-OH; 1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4
      methoxyphenyl)ethane] as the primary degradation product. The chiral high
      performance liquid chromatography (HPLC) analysis revealed that the isolate
      possesses high enantioselectivity favoring the formation of (S)-Mono-OH (nearly
      100%). Accompanied by the sequential O-demethylation to form the bis-phenolic
      derivative Bis-OH [1,1,1-trichloro-2,2-bis(4-hydroxyphenyl)ethane], oxidative
      dechlorination of the side chain proceeded, and monophenolic carboxylic acid
      accumulated, followed by the formation of multiple unidentified polar degradation
      products. The breakdown proceeded more rapidly when reductively dechlorinated
      (dichloro-form) methoxychlor was applied as the initial substrate. The resultant
      carboxylic acids and polar degradation products are likely further biodegraded by
      ubiquitous bacteria. The isolate possibly plays an important role for complete
      degradation (mineralization) of methoxychlor by providing the readily
      biodegradable substrates.

PMID- 22635992
TI  - Real-time PCR methodology for selective detection of viable Escherichia coli
      O157:H7 cells by targeting Z3276 as a genetic marker.
AB  - The goal of this study was to develop a sensitive, specific, and accurate method
      for the selective detection of viable Escherichia coli O157:H7 cells in foods. A
      unique open reading frame (ORF), Z3276, was identified as a specific genetic
      marker for the detection of E. coli O157:H7. We developed a real-time PCR assay
      with primers and probe targeting ORF Z3276 and confirmed that this assay was
      sensitive and specific for E. coli O157:H7 strains (n = 298). Using this assay,
      we can detect amounts of genomic DNA of E. coli O157:H7 as low as a few CFU
      equivalents. Moreover, we have developed a new propidium monoazide (PMA)-real
      time PCR protocol that allows for the clear differentiation of viable from dead
      cells. In addition, the protocol was adapted to a 96-well plate format for easy
      and consistent handling of a large number of samples. Amplification of DNA from
      PMA-treated dead cells was almost completely inhibited, in contrast to the
      virtually unaffected amplification of DNA from PMA-treated viable cells. With
      beef spiked simultaneously with 8 * 10(7) dead cells/g and 80 CFU viable cells/g,
      we were able to selectively detect viable E. coli O157:H7 cells with an 8-h
      enrichment. In conclusion, this PMA-real-time PCR assay offers a sensitive and
      specific means to selectively detect viable E. coli O157:H7 cells in spiked beef.
      It also has the potential for high-throughput selective detection of viable E.
      coli O157:H7 cells in other food matrices and, thus, will have an impact on the
      accurate microbiological and epidemiological monitoring of food safety and
      environmental sources.

PMID- 22635994
TI  - Identification and molecular characterization of class 1 integrons in
      multiresistant Escherichia coli isolates from poultry litter.
AB  - This study describes the prevalence of arrays of class 1 integron cassettes and
      Qnr determinants (A, B, and S) in 19 fluoroquinolone-resistant Escherichia coli
      isolates from chicken litter. qnrS and qnrA were the predominant genes in these
      fluoroquinolone-resistant isolates, and an uncommon array of aacA4-catB3-dfrA1
      gene cassettes from a class1 integron was found. Additionally, aadA1 and dfrA1
      gene cassettes, encoding resistance to streptomycin and trimethoprim, constituted
      the most common genes identified and was located on megaplasmids as well on the
      chromosome. Antibiotic resistance, pulsed-field gel electrophoresis (PFGE), and
      plasmid data suggest a genetically diverse origin of poultry E. coli isolates.

PMID- 22635995
TI  - Discovery of a trans-dichloroethene-respiring Dehalogenimonas species in the
      1,1,2,2-tetrachloroethane-dechlorinating WBC-2 consortium.
AB  - The WBC-2 consortium is an organohalide-respiring anaerobic microbial enrichment
      culture capable of dechlorinating 1,1,2,2-tetrachloroethane (TeCA) to ethene. In
      the WBC-2 culture, TeCA is first transformed to trans-dichloroethene (tDCE) by
      dichloroelimination; tDCE is subsequently transformed to vinyl chloride (VC) and
      then to ethene by hydrogenolysis. Analysis of 16S rRNA gene clone libraries from
      culture DNA revealed sequences from three putative dechlorinating organisms
      belonging to Dehalococcoides, Dehalobacter, and Dehalogenimonas genera.
      Quantitative PCR primers were designed for each of these sequences, and their
      abundance was quantified in enrichment cultures over time. These data revealed
      that complete dechlorination of TeCA to ethene involves all three organisms.
      Dehalobacter spp. grew during the dihaloelimination of TeCA to tDCE, while
      Dehalococcoides and Dehalogenimonas spp. grew during hydrogenolysis of tDCE to
      ethene. This is the first time a genus other than Dehalococcoides has been
      implicated in dechlorination of tDCE to VC.

PMID- 22635996
TI  - Reclamation of ampicillin sensitivity for the genetic manipulation of Legionella
      pneumophila.
AB  - Research on Legionella pneumophila, the causative agent of Legionnaires' disease,
      has been hampered due to the lack of selectable markers for genetic manipulation.
      We report the construction of a mutant strain of L. pneumophila lacking loxA, a
      chromosomally encoded beta-lactamase, that has enhanced sensitivity to
      ampicillin. Also described are a method for converting Legionella strains to
      ampicillin sensitivity and conditions for utilizing bla as a selectable marker.

PMID- 22635997
TI  - Oral spirochetes implicated in dental diseases are widespread in normal human
      subjects and carry extremely diverse integron gene cassettes.
AB  - The NIH Human Microbiome Project (HMP) has produced several hundred metagenomic
      data sets, allowing studies of the many functional elements in human-associated
      microbial communities. Here, we survey the distribution of oral spirochetes
      implicated in dental diseases in normal human individuals, using recombination
      sites associated with the chromosomal integron in Treponema genomes, taking
      advantage of the multiple copies of the integron recombination sites (repeats) in
      the genomes, and using a targeted assembly approach that we have developed. We
      find that integron-containing Treponema species are present in ~80% of the normal
      human subjects included in the HMP. Further, we are able to de novo assemble the
      integron gene cassettes using our constrained assembly approach, which employs a
      unique application of the de Bruijn graph assembly information; most of these
      cassette genes were not assembled in whole-metagenome assemblies and could not be
      identified by mapping sequencing reads onto the known reference Treponema genomes
      due to the dynamic nature of integron gene cassettes. Our study significantly
      enriches the gene pool known to be carried by Treponema chromosomal integrons,
      totaling 826 (598 97% nonredundant) genes. We characterize the functions of these
      gene cassettes: many of these genes have unknown functions. The integron gene
      cassette arrays found in the human microbiome are extraordinarily dynamic, with
      different microbial communities sharing only a small number of common genes.

PMID- 22635998
TI  - Modeling of phenoxy acid herbicide mineralization and growth of microbial
      degraders in 15 soils monitored by quantitative real-time PCR of the functional
      tfdA gene.
AB  - Mineralization potentials, rates, and kinetics of the three phenoxy acid (PA)
      herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2
      methylphenoxyacetic acid (MCPA), and 2-(4-chloro-2-methylphenoxy)propanoic acid
      (MCPP), were investigated and compared in 15 soils collected from five
      continents. The mineralization patterns were fitted by zero/linear or exponential
      growth forms of the three-half-order models and by logarithmic (log), first
      order, or zero-order kinetic models. Prior and subsequent to the mineralization
      event, tfdA genes were quantified using real-time PCR to estimate the genetic
      potential for degrading PA in the soils. In 25 of the 45 mineralization
      scenarios, ~60% mineralization was observed within 118 days. Elevated
      concentrations of tfdA in the range 1 * 10(5) to 5 * 10(7) gene copies g(-1) of
      soil were observed in soils where mineralization could be described by using
      growth-linked kinetic models. A clear trend was observed that the mineralization
      rates of the three PAs occurred in the order 2,4-D > MCPA > MCPP, and a
      correlation was observed between rapid mineralization and soils exposed to PA
      previously. Finally, for 2,4-D mineralization, all seven mineralization patterns
      which were best fitted by the exponential model yielded a higher tfdA gene
      potential after mineralization had occurred than the three mineralization
      patterns best fitted by the Lin model.

PMID- 22635999
TI  - Effects of subinhibitory concentrations of menthol on adaptation, morphological,
      and gene expression changes in enterohemorrhagic Escherichia coli.
AB  - Menthol (C(10)H(20)O) possesses antibacterial activity; nevertheless, bacterial
      adaptation to this compound has never been studied. Here we report that
      precultivation of enterohemorrhagic Escherichia coli (EHEC) strains in increasing
      subinhibitory (SI) concentrations of menthol significantly elevates (4- to 16
      fold) their resistance to menthol. Concomitant morphological alterations included
      the appearance of mucoid colonies and reduced biofilm production. Scanning
      electron microscopy (SEM) examination revealed suppressed curli formation in
      menthol-adapted cells. Expression of the gene cpsB10 (encoding one of the enzymes
      responsible for colanic acid production) was elevated in response to SI
      concentrations of menthol in a laboratory E. coli strain, whereas expression in
      an rcsC null mutant was reduced, implicating a partial role for the Rcs
      phosphorelay system in mediating the menthol signal. Adaptation to menthol also
      reduced expression of the locus of enterocyte effacement-encoded regulator (Ler).
      This reduction, together with reduced curli and biofilm formation and elevated
      mucoidity, suggests a general reduction in bacterial virulence following
      adaptation to menthol. Our results thus suggest menthol as a potential lead in
      the recently emerging alternative strategy of targeting bacterial virulence
      factors to develop new types of anti-infective agents.

PMID- 22636000
TI  - Involvement of a putative cyclic amp receptor protein (CRP)-like binding sequence
      and a CRP-like protein in glucose-mediated catabolite repression of thn genes in
      Rhodococcus sp. strain TFB.
AB  - Glucose catabolite repression of tetralin catabolic genes in Rhodococcus sp.
      strain TFB was shown to be exerted by a protein homologous to transcriptional
      regulators of the cyclic AMP receptor (CRP)-FNR family. The protein was detected
      bound to putative CRP-like boxes localized at the promoters of the thnA1 and thnS
      genes.

PMID- 22636001
TI  - Upregulation of plasmid genes during stationary phase in Synechocystis sp. strain
      PCC 6803, a cyanobacterium.
AB  - We analyzed DNA microarrays to identify highly expressed genes during stationary
      phase growth of Synechocystis sp. PCC 6803. Many identified genes are on
      endogenous plasmids, with copy numbers between 0.4 and 7 per chromosome. The
      promoters of such genes will be useful for synthetic biology applications with
      this phototrophic host.

PMID- 22636002
TI  - Patterns of [FeFe] hydrogenase diversity in the gut microbial communities of
      lignocellulose-feeding higher termites.
AB  - Hydrogen is the central free intermediate in the degradation of wood by termite
      gut microbes and can reach concentrations exceeding those measured for any other
      biological system. Degenerate primers targeting the largest family of [FeFe]
      hydrogenases observed in a termite gut metagenome have been used to explore the
      evolution and representation of these enzymes in termites. Sequences were cloned
      from the guts of the higher termites Amitermes sp. strain Cost010, Amitermes sp.
      strain JT2, Gnathamitermes sp. strain JT5, Microcerotermes sp. strain Cost008,
      Nasutitermes sp. strain Cost003, and Rhyncotermes sp. strain Cost004. Each gut
      sample harbored a more rich and evenly distributed population of hydrogenase
      sequences than observed previously in the guts of lower termites and Cryptocercus
      punctulatus. This accentuates the physiological importance of hydrogen for higher
      termite gut ecosystems and may reflect an increased metabolic burden, or
      metabolic opportunity, created by a lack of gut protozoa. The sequences were
      phylogenetically distinct from previously sequenced [FeFe] hydrogenases.
      Phylogenetic and UniFrac comparisons revealed congruence between host phylogeny
      and hydrogenase sequence library clustering patterns. This may reflect the
      combined influences of the stable intimate relationship of gut microbes with
      their host and environmental alterations in the gut that have occurred over the
      course of termite evolution. These results accentuate the physiological
      importance of hydrogen to termite gut ecosystems.

PMID- 22636003
TI  - Intricate interactions between the bloom-forming cyanobacterium Microcystis
      aeruginosa and foreign genetic elements, revealed by diversified clustered
      regularly interspaced short palindromic repeat (CRISPR) signatures.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) confer
      sequence-dependent, adaptive resistance in prokaryotes against viruses and
      plasmids via incorporation of short sequences, called spacers, derived from
      foreign genetic elements. CRISPR loci are thus considered to provide records of
      past infections. To describe the host-parasite (i.e., cyanophages and plasmids)
      interactions involving the bloom-forming freshwater cyanobacterium Microcystis
      aeruginosa, we investigated CRISPR in four M. aeruginosa strains and in two
      previously sequenced genomes. The number of spacers in each locus was larger than
      the average among prokaryotes. All spacers were strain specific, except for a
      string of 11 spacers shared in two closely related strains, suggesting
      diversification of the loci. Using CRISPR repeat-based PCR, 24 CRISPR genotypes
      were identified in a natural cyanobacterial community. Among 995 unique spacers
      obtained, only 10 sequences showed similarity to M. aeruginosa phage Ma-LMM01. Of
      these, six spacers showed only silent or conservative nucleotide mutations
      compared to Ma-LMM01 sequences, suggesting a strategy by the cyanophage to avert
      CRISPR immunity dependent on nucleotide identity. These results imply that host
      phage interactions can be divided into M. aeruginosa-cyanophage combinations
      rather than pandemics of population-wide infectious cyanophages. Spacer
      similarity also showed frequent exposure of M. aeruginosa to small cryptic
      plasmids that were observed only in a few strains. Thus, the diversification of
      CRISPR implies that M. aeruginosa has been challenged by diverse communities
      (almost entirely uncharacterized) of cyanophages and plasmids.

PMID- 22636004
TI  - Predominance of a versatile-peroxidase-encoding gene, mnp4, as demonstrated by
      gene replacement via a gene targeting system for Pleurotus ostreatus.
AB  - Pleurotus ostreatus (the oyster mushroom) and other white rot filamentous
      basidiomycetes are key players in the global carbon cycle. P. ostreatus is also a
      commercially important edible fungus with medicinal properties and is important
      for biotechnological and environmental applications. Efficient gene targeting via
      homologous recombination (HR) is a fundamental tool for facilitating
      comprehensive gene function studies. Since the natural HR frequency in Pleurotus
      transformations is low (2.3%), transformed DNA is predominantly integrated
      ectopically. To overcome this limitation, a general gene targeting system was
      developed by producing a P. ostreatus PC9 homokaryon Deltaku80 strain, using
      carboxin resistance complemented by the development of a protocol for hygromycin
      B resistance protoplast-based DNA transformation and homokaryon isolation. The
      Deltaku80 strain exhibited exclusive (100%) HR in the integration of transforming
      DNA, providing a high efficiency of gene targeting. Furthermore, the Deltaku80
      strains produced showed a phenotype similar to that of the wild-type PC9 strain,
      with similar growth fitness, ligninolytic functionality, and capability of mating
      with the incompatible strain PC15 to produce a dikaryon which retained its
      resistance to the corresponding selection and was capable of producing typical
      fruiting bodies. The applicability of this system is demonstrated by inactivation
      of the versatile peroxidase (VP) encoded by mnp4. This enzyme is part of the
      ligninolytic system of P. ostreatus, being one of the nine members of the
      manganese-peroxidase (MnP) gene family, and is the predominantly expressed VP in
      Mn(2+)-deficient media. mnp4 inactivation provided a direct proof that mnp4
      encodes a key VP responsible for the Mn(2+)-dependent and Mn(2+)-independent
      peroxidase activity under Mn(2+)-deficient culture conditions.

PMID- 22636005
TI  - Genetically modified strains of Ralstonia eutropha H16 with beta-ketothiolase
      gene deletions for production of copolyesters with defined 3-hydroxyvaleric acid
      contents.
AB  - beta-Ketothiolases catalyze the first step of poly(3-hydroxybutyrate) [poly(3HB)]
      biosynthesis in bacteria by condensation of two acetyl coenzyme A (acetyl-CoA)
      molecules to acetoacetyl-CoA and also take part in the degradation of fatty
      acids. During growth on propionate or valerate, Ralstonia eutropha H16 produces
      the copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [poly(3HB-co-3HV)]. In
      R. eutropha, 15 beta-ketothiolase homologues exist. The synthesis of 3
      hydroxybutyryl-CoA (3HB-CoA) could be significantly reduced in an 8-fold mutant
      (Lindenkamp et al., Appl. Environ. Microbiol. 76:5373-5382, 2010). In this study,
      a 9-fold mutant deficient in nine beta-ketothiolase gene homologues (phaA, bktB,
      H16_A1713, H16_B1771, H16_A1528, H16_B0381, H16_B1369, H16_A0170, and pcaF) was
      generated. In order to examine the polyhydroxyalkanoate production capacity when
      short- or long-chain and even- or odd-chain-length fatty acids were provided as
      carbon sources, the growth and storage behavior of several mutants from the
      previous study and the newly generated 9-fold mutant were analyzed. Propionate,
      valerate, octanoate, undecanoic acid, or oleate was chosen as the sole carbon
      source. On octanoate, no significant differences in growth or storage behavior
      were observed between wild-type R. eutropha and the mutants. In contrast, during
      the growth on oleate of a multiple mutant lacking phaA, bktB, and H16_A0170,
      diminished poly(3HB) accumulation occurred. Surprisingly, the amount of
      accumulated poly(3HB) in the multiple mutants grown on gluconate differed; it was
      much lower than that on oleate. The beta-ketothiolase activity toward acetoacetyl
      CoA in H16DeltaphaA and all the multiple mutants remained 10-fold lower than the
      activity of the wild type, regardless of which carbon source, oleate or
      gluconate, was employed. During growth on valerate as a sole carbon source, the 9
      fold mutant accumulated almost a poly(3-hydroxyvalerate) [poly(3HV)]
      homopolyester with 99 mol% 3HV constituents.

PMID- 22636006
TI  - Genome sequence and mutational analysis of plant-growth-promoting bacterium
      Agrobacterium tumefaciens CCNWGS0286 Isolated from a zinc-lead mine tailing.
AB  - The plant-growth-promoting bacterium Agrobacterium tumefaciens CCNWGS0286,
      isolated from the nodules of Robinia pseudoacacia growing in zinc-lead mine
      tailings, both displayed high metal resistance and enhanced the growth of Robinia
      plants in a metal-contaminated environment. Our goal was to determine whether
      bacterial metal resistance or the capacity to produce phytohormones had a larger
      impact on the growth of host plants under zinc stress. Eight zinc-sensitive
      mutants and one zinc-sensitive mutant with reduced indole-3-acetic acid (IAA)
      production were obtained by transposon mutagenesis. Analysis of the genome
      sequence and of transcription via reverse transcriptase PCR (RT-PCR) combined
      with transposon gene disruptions revealed that ZntA-4200 and the transcriptional
      regulator ZntR1 played important roles in the zinc homeostasis of A. tumefaciens
      CCNWGS0286. In addition, interruption of a putative oligoketide cyclase/lipid
      transport protein reduced IAA synthesis and also showed reduced zinc and cadmium
      resistance but had no influence on copper resistance. In greenhouse studies, R.
      pseudoacacia inoculated with A. tumefaciens CCNWGS0286 displayed a significant
      increase in biomass production over that without inoculation, even in a zinc
      contaminated environment. Interestingly, the differences in plant biomass
      improvement among A. tumefaciens CCNWGS0286, A. tumefaciens C58, and zinc
      sensitive mutants 12-2 (zntA::Tn5) and 15-6 (low IAA production) revealed that
      phytohormones, rather than genes encoding zinc resistance determinants, were the
      dominant factor in enhancing plant growth in contaminated soil.

PMID- 22636007
TI  - Microbiological and physicochemical characterization of small-scale cocoa
      fermentations and screening of yeast and bacterial strains to develop a defined
      starter culture.
AB  - Spontaneous cocoa bean fermentations performed under bench- and pilot-scale
      conditions were studied using an integrated microbiological approach with culture
      dependent and culture-independent techniques, as well as analyses of target
      metabolites from both cocoa pulp and cotyledons. Both fermentation ecosystems
      reached equilibrium through a two-phase process, starting with the simultaneous
      growth of the yeasts (with Saccharomyces cerevisiae as the dominant species) and
      lactic acid bacteria (LAB) (Lactobacillus fermentum and Lactobacillus plantarum
      were the dominant species), which were gradually replaced by the acetic acid
      bacteria (AAB) (Acetobacter tropicalis was the dominant species). In both
      processes, a sequence of substrate consumption (sucrose, glucose, fructose, and
      citric acid) and metabolite production kinetics (ethanol, lactic acid, and acetic
      acid) similar to that of previous, larger-scale fermentation experiments was
      observed. The technological potential of yeast, LAB, and AAB isolates was
      evaluated using a polyphasic study that included the measurement of stress
      tolerant growth and fermentation kinetic parameters in cocoa pulp media. Overall,
      strains L. fermentum UFLA CHBE8.12 (citric acid fermenting, lactic acid
      producing, and tolerant to heat, acid, lactic acid, and ethanol), S. cerevisiae
      UFLA CHYC7.04 (ethanol producing and tolerant to acid, heat, and ethanol), and
      Acetobacter tropicalis UFLA CHBE16.01 (ethanol and lactic acid oxidizing, acetic
      acid producing, and tolerant to acid, heat, acetic acid, and ethanol) were
      selected to form a cocktail starter culture that should lead to better-controlled
      and more-reliable cocoa bean fermentation processes.

PMID- 22636008
TI  - Archaeal tetrathionate hydrolase goes viral: secretion of a sulfur metabolism
      enzyme in the form of virus-like particles.
AB  - In the course of screening for virus-host systems in extreme thermal
      environments, we have isolated a strain of the hyperthermophilic archaeaon
      Acidianus hospitalis producing unusual filamentous particles with a zipper-like
      appearance. The particles were shown to represent a secreted form of a genuine
      cellular enzyme, tetrathionate hydrolase, involved in sulfur metabolism.

PMID- 22636009
TI  - Engineering of a xylose metabolic pathway in Rhodococcus strains.
AB  - The two metabolically versatile actinobacteria Rhodococcus opacus PD630 and R.
      jostii RHA1 can efficiently convert diverse organic substrates into neutral
      lipids mainly consisting of triacylglycerol (TAG), the precursor of energy-rich
      hydrocarbon. Neither, however, is able to utilize xylose, the important component
      present in lignocellulosic biomass, as the carbon source for growth and lipid
      accumulation. In order to broaden their substrate utilization range, the
      metabolic pathway of d-xylose utilization was introduced into these two strains.
      This was accomplished by heterogenous expression of two well-selected genes,
      xylA, encoding xylose isomerase, and xylB, encoding xylulokinase from
      Streptomyces lividans TK23, under the control of the tac promoter with an
      Escherichia coli-Rhodococcus shuttle vector. The recombinant R. jostii RHA1
      bearing xylA could grow on xylose as the sole carbon source, and additional
      expression of xylB further improved the biomass yield. The recombinant could
      consume both glucose and xylose in the sugar mixture, although xylose metabolism
      was still affected by the presence of glucose. The xylose metabolic pathway was
      also introduced into the high-lipid-producing strain R. opacus PD630 by
      expression of xylA and xylB. Under nitrogen-limited conditions, the fatty acid
      composition was determined, and lipid produced from xylose by recombinants of R.
      jostii RHA1 and R. opacus PD630 carrying xylA and xylB represented up to 52.5%
      and 68.3% of the cell dry weight (CDW), respectively. This work demonstrates that
      it is feasible to produce lipid from the sugars, including xylose, derived from
      renewable feedstock by genetic modification of rhodococcus strains.

PMID- 22636010
TI  - Characterization of geographically distinct bacterial communities associated with
      coral mucus produced by Acropora spp. and Porites spp.
AB  - Acropora and Porites corals are important reef builders in the Indo-Pacific and
      Caribbean. Bacteria associated with mucus produced by Porites spp. and Acropora
      spp. from Caribbean (Punta Maroma, Mexico) and Indo-Pacific (Hoga and Sampela,
      Indonesia) reefs were determined. Analysis of pyrosequencing libraries showed
      that bacterial communities from Caribbean corals were significantly more diverse
      (H', 3.18 to 4.25) than their Indonesian counterparts (H', 2.54 to 3.25).
      Dominant taxa were Gammaproteobacteria, Alphaproteobacteria, Firmicutes, and
      Cyanobacteria, which varied in relative abundance between coral genera and
      region. Distinct coral host-specific communities were also found; for example,
      Clostridiales were dominant on Acropora spp. (at Hoga and the Mexican Caribbean)
      compared to Porites spp. and seawater. Within the Gammproteobacteria, Halomonas
      spp. dominated sequence libraries from Porites spp. (49%) and Acropora spp.
      (5.6%) from the Mexican Caribbean, compared to the corresponding Indonesian coral
      libraries (<2%). Interestingly, with the exception of Porites spp. from the
      Mexican Caribbean, there was also a ubiquity of Psychrobacter spp., which
      dominated Acropora and Porites libraries from Indonesia and Acropora libraries
      from the Caribbean. In conclusion, there was a dominance of Halomonas spp.
      (associated with Acropora and Porites [Mexican Caribbean]), Firmicutes
      (associated with Acropora [Mexican Caribbean] and with Acropora and Porites
      [Hoga]), and Cyanobacteria (associated with Acropora and Porites [Hoga] and
      Porites [Sampela]). This is also the first report describing geographically
      distinct Psychrobacter spp. associated with coral mucus. In addition, the
      predominance of Clostridiales associated with Acropora spp. provided additional
      evidence for coral host-specific microorganisms.

PMID- 22636011
TI  - White mutants of chloroperoxidase-secreting Caldariomyces fumago as superior
      production strains, revealing an interaction between pigmentation and enzyme
      secretion.
AB  - By mutant-colony screening of Caldariomyces fumago, several white mutants were
      isolated that are superior strains for the production of the valuable enzyme
      chloroperoxidase (CPO). Their culture supernatant lacks the contaminating dark
      pigment, which simplifies downstream processing. Furthermore, the CPO content
      increased significantly faster than the wild-type rate, which uncovers possible
      interactions between pigmentation and enzyme secretion.

PMID- 22636012
TI  - Cofermentation of glucose, xylose, and cellobiose by the beetle-associated yeast
      Spathaspora passalidarum.
AB  - Fermentation of cellulosic and hemicellulosic sugars from biomass could resolve
      food-versus-fuel conflicts inherent in the bioconversion of grains. However, the
      inability to coferment glucose and xylose is a major challenge to the economical
      use of lignocellulose as a feedstock. Simultaneous cofermentation of glucose,
      xylose, and cellobiose is problematic for most microbes because glucose represses
      utilization of the other saccharides. Surprisingly, the ascomycetous, beetle
      associated yeast Spathaspora passalidarum, which ferments xylose and cellobiose
      natively, can also coferment these two sugars in the presence of 30 g/liter
      glucose. S. passalidarum simultaneously assimilates glucose and xylose
      aerobically, it simultaneously coferments glucose, cellobiose, and xylose with an
      ethanol yield of 0.42 g/g, and it has a specific ethanol production rate on
      xylose more than 3 times that of the corresponding rate on glucose. Moreover, an
      adapted strain of S. passalidarum produced 39 g/liter ethanol with a yield of
      0.37 g/g sugars from a hardwood hydrolysate. Metabolome analysis of S.
      passalidarum before onset and during the fermentations of glucose and xylose
      showed that the flux of glycolytic intermediates is significantly higher on
      xylose than on glucose. The high affinity of its xylose reductase activities for
      NADH and xylose combined with allosteric activation of glycolysis probably
      accounts in part for its unusual capacities. These features make S. passalidarum
      very attractive for studying regulatory mechanisms enabling bioconversion of
      lignocellulosic materials by yeasts.

PMID- 22636013
TI  - Proteomic analysis of Bacillus thuringiensis at different growth phases by using
      an automated online two-dimensional liquid chromatography-tandem mass
      spectrometry strategy.
AB  - The proteome of a new Bacillus thuringiensis subsp. kurstaki strain, 4.0718, from
      the middle vegetative (T(1)), early sporulation (T(2)), and late sporulation
      (T(3)) phases was analyzed using an integrated liquid chromatography (LC)-based
      protein identification system. The system comprised two-dimensional (2D) LC
      coupled with nanoscale electrospray ionization (ESI) tandem mass spectrometry
      (MS/MS) on a high-resolution hybrid mass spectrometer with an automated data
      analysis system. After deletion of redundant proteins from the different batches
      and B. thuringiensis subspecies, 918, 703, and 778 proteins were identified in
      the respective three phases. Their molecular masses ranged from 4.6 Da to 477.4
      Da, and their isoelectric points ranged from 4.01 to 11.84. Function clustering
      revealed that most of the proteins in the three phases were functional metabolic
      proteins, followed by proteins participating in cell processes. Small molecular
      and macromolecular metabolic proteins were further classified according to the
      Kyoto Encyclopedia of Genes and Genome and BioCyc metabolic pathway database.
      Three protoxins (Cry2Aa, Cry1Aa, and Cry1Ac) as well as a series of potential
      intracellular active factors were detected. Many significant proteins related to
      spore and crystal formation, including sporulation proteins, help proteins,
      chaperones, and so on, were identified. The expression patterns of two identified
      proteins, CotJc and glutamine synthetase, were validated by Western blot
      analysis, which further confirmed the MS results. This study is the first to use
      shotgun technology to research the proteome of B. thuringiensis. Valuable
      experimental data are provided regarding the methodology of analyzing the B.
      thuringiensis proteome (which can be used to produce insecticidal crystal
      proteins) and have been added to the related protein database.

PMID- 22636067
TI  - Cancer peptide vaccine therapy developed from oncoantigens identified through
      genome-wide expression profile analysis for bladder cancer.
AB  - OBJECTIVE: The field of cancer vaccine therapy is currently expected to become
      the fourth option in the treatment of cancer after surgery, chemotherapy and
      radiation therapy. We developed a novel cancer peptide vaccine therapy for
      bladder cancer through a genome-wide expression profile analysis. METHODS: Among
      a number of oncoproteins that are transactivated in cancer cells, we focused on M
      phase phosphoprotein 1 and DEP domain containing 1, both of which are cancer
      testis antigens playing critical roles in the growth of bladder cancer cells, as
      candidate molecules for the development of drugs for bladder cancer. In an
      attempt to identify the peptide epitope from these oncoantigens, we conducted a
      clinical trial using these peptides for patients with advanced bladder cancer.
      RESULTS: We identified HLA-A24-restricted peptide epitopes corresponding to parts
      of M phase phosphoprotein 1 and DEP domain containing 1 proteins, which could
      induce peptide-specific cytotoxic T lymphocytes. Using these peptides, we found
      that M phase phosphoprotein 1- and DEP domain containing 1-derived peptide
      vaccines could be well tolerated without any serious adverse events, and
      effectively induced peptide-specific cytotoxic T lymphocytes in vivo.
      CONCLUSIONS: The novel approach adopted in the treatment with peptide vaccines is
      considered to be a promising therapy for bladder cancer.

PMID- 22636169
TI  - Relative contribution of SKCa and TREK1 channels in purinergic and nitrergic
      neuromuscular transmission in the rat colon.
AB  - Purinergic and nitrergic neurotransmission predominantly mediate inhibitory
      neuromuscular transmission in the rat colon. We studied the sensitivity of both
      purinergic and nitrergic pathways to spadin, a TWIK-related potassium channel 1
      (TREK1) inhibitor, apamin, a small-conductance calcium-activated potassium
      channel blocker and 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), a
      specific inhibitor of soluble guanylate cyclase. TREK1 expression was detected by
      RT-PCR in the rat colon. Patch-clamp experiments were performed on cells
      expressing hTREK1 channels. Spadin (1 MUM) reduced currents 1) in basal
      conditions 2) activated by stretch, and 3) with arachidonic acid (AA; 10 MUM). l
      Methionine (1 mM) or l-cysteine (1 mM) did not modify currents activated by AA.
      Microelectrode and muscle bath studies were performed on rat colon samples. l
      Methionine (2 mM), apamin (1 MUM), ODQ (10 MUM), and N(omega)-nitro-l-arginine (l
      NNA; 1 mM) depolarized smooth muscle cells and increased motility. These effects
      were not observed with spadin (1 MUM). Purinergic and nitrergic inhibitory
      junction potentials (IJP) were studied by incubating the tissue with l-NNA (1 mM)
      or MRS2500 (1 MUM). Both purinergic and nitrergic IJP were unaffected by spadin.
      Apamin reduced both IJP with a different potency and maximal effect for each. ODQ
      concentration dependently abolished nitrergic IJP without affecting purinergic
      IJP. Similar effects were observed in hyperpolarizations induced by sodium
      nitroprusside (1 MUM) and nitrergic relaxations induced by electrical
      stimulation. We propose a pharmacological approach to characterize the pathways
      and function of purinergic and nitrergic neurotransmission. Nitrergic
      neurotransmission, which is mediated by cyclic guanosine monophosphate, is
      insensitive to spadin, an effective TREK1 channel inhibitor. Both purinergic and
      nitrergic neurotransmission are inhibited by apamin but with different relative
      sensitivity.

PMID- 22636202
TI  - Liberating reason from the passions: overriding intuitionist moral judgments
      through emotion reappraisal.
AB  - A classic problem in moral psychology concerns whether and when moral judgments
      are driven by intuition versus deliberate reasoning. In this investigation, we
      explored the role of reappraisal, an emotion-regulation strategy that involves
      construing an emotion-eliciting situation in a way that diminishes the intensity
      of the emotional experience. We hypothesized that although emotional reactions
      evoke initial moral intuitions, reappraisal weakens the influence of these
      intuitions, leading to more deliberative moral judgments. Three studies of moral
      judgments in emotionally evocative, disgust-eliciting moral dilemmas supported
      our hypothesis. A greater tendency to reappraise was related to fewer intuition
      based judgments (Study 1). Content analysis of open-ended descriptions of moral
      reasoning processes revealed that reappraisal was associated with longer time
      spent in deliberation and with fewer intuitionist moral judgments (Study 2).
      Finally, in comparison with participants who simply watched an emotion-inducing
      film, participants who had been instructed to reappraise their reactions while
      watching the film subsequently reported less intense emotional reactions to moral
      dilemmas, and these dampened reactions led, in turn, to fewer intuitionist moral
      judgments (Study 3).

PMID- 22636255
TI  - Exercise partly reverses the effect of maternal separation on hippocampal
      proteins in 6-hydroxydopamine-lesioned rat brain.
AB  - Animals subjected to maternal separation stress during the early stages of
      development display behavioural, endocrine and growth factor abnormalities that
      mirror the clinical findings in anxiety/depression. In addition, maternal
      separation has been shown to exacerbate the behavioural deficits induced by 6
      hydroxydopamine (6-OHDA) in a rat model of Parkinson's disease. In contrast,
      voluntary exercise reduced the detrimental effects of 6-OHDA in the rat model.
      The beneficial effects of exercise appeared to be largely due to compensation in
      the non-lesioned hemisphere. The aim of the present study was to investigate
      whether voluntary exercise for 3 weeks could reverse the effects of maternal
      separation in rats challenged with the neurotoxin 6-OHDA infused into the medial
      forebrain bundle after 1 week of exercise, at postnatal day 60. The rats were
      killed 2 weeks later, at postnatal day 74. Their brains were dissected and the
      hippocampus rapidly removed for proteomic analysis by isobaric tagging (iTRAQ)
      and quantification of peptides by matrix-assisted laser desorption/ionization
      tandem mass spectrometry (MALDI-MS/MS). Maternal separation upregulated
      hippocampal proteins functionally involved in energy metabolism (nucleoside
      diphosphate kinase B, enolase and triosephosphate isomerase) and synaptic
      plasticity (alpha-synuclein, tenascin-R, Ba1-667, brevican and neurocan core
      protein) in the non-lesioned hemisphere. Exercise reversed many of these changes
      by downregulating the levels of hippocampal proteins functionally associated with
      energy metabolism (nucleoside diphosphate kinase B, enolase and triosephosphate
      isomerase) and synaptic plasticity (alpha-synuclein, tenascin-R, Ba1-667,
      brevican and neurocan core protein) in the non-lesioned hemisphere of rats
      subjected to maternal separation. Exercise and maternal separation therefore
      appeared to have opposing effects on the hippocampus in the non-lesioned
      hemisphere of the rat brain. Exercise seemed partly to reverse the effects of
      maternal separation stress on these proteins in the non-lesioned hemisphere. The
      partial reversal of maternal separation-induced proteins by exercise in the non
      lesioned side sheds some insight into the mechanism by which exercise alters the
      molecular role players involved in determining the consequences of early life
      stress.

PMID- 22636256
TI  - Mitochondrial function in human skeletal muscle following high-altitude exposure.
AB  - Studies regarding mitochondrial modifications in human skeletal muscle following
      acclimatization to high altitude are conflicting, and these inconsistencies may
      be due to the prevalence of representing mitochondrial function through static
      and isolated measurements of specific mitochondrial characteristics. The aim of
      this study, therefore, was to investigate mitochondrial function in response to
      high-altitude acclimatization through measurements of respiratory control in the
      vastus lateralis muscle. Skeletal muscle biopsies were obtained from 10 lowland
      natives prior to and again after a total of 9-11 days of exposure to 4559 m. High
      resolution respirometry was performed on the muscle samples to compare
      respiratory chain function and respiratory capacities. Respirometric analysis
      revealed that mitochondrial function was largely unaffected, because high
      altitude exposure did not affect the capacity for fat oxidation or individualized
      respiration capacity through either complex I or complex II. Respiratory chain
      function remained unaltered, because neither coupling nor respiratory control
      changed in response to hypoxic exposure. High-altitude acclimatization did,
      however, show a tendency (P = 0.059) to limit mass-specific maximal oxidative
      phosphorylation capacity. These data suggest that 9-11 days of exposure to high
      altitude do not markedly modify integrated measures of mitochondrial functional
      capacity in skeletal muscle despite significant decrements in the concentrations
      of enzymes involved in the tricarboxylic acid cycle and oxidative
      phosphorylation.

PMID- 22636320
TI  - Monocyte-derived dendritic cells from breast cancer patients are biased to induce
      CD4+CD25+Foxp3+ regulatory T cells.
AB  - DCs orchestrate immune responses contributing to the pattern of response
      developed. In cancer, DCs may play a dysfunctional role in the induction of
      CD4(+)CD25(+)Foxp3(+) Tregs, contributing to immune evasion. We show here that Mo
      DCs from breast cancer patients show an altered phenotype and induce
      preferentially Tregs, a phenomenon that occurred regardless of DC maturation
      stimulus (sCD40L, cytokine cocktail, TNF-alpha, and LPS). The Mo-DCs of patients
      induced low proliferation of allogeneic CD3(+)CD25(neg)Foxp3(neg) cells, which
      after becoming CD25(+), suppressed mitogen-stimulated T cells. Contrastingly, Mo
      DCs from healthy donors induced a stronger proliferative response, a low
      frequency of CD4(+)CD25(+)Foxp3(+) with no suppressive activity. Furthermore,
      healthy Mo-DCs induced higher levels of IFN-gamma, whereas the Mo-DCs of patients
      induced higher levels of bioactive TGF-beta1 and IL-10 in cocultures with
      allogeneic T cells. Interestingly, TGF-beta1 blocking with mAb in cocultures was
      not enough to completely revert the Mo-DCs of patients' bias toward Treg
      induction. Altogether, these findings should be considered in immunotherapeutic
      approaches for cancer based on Mo-DCs.

PMID- 22636319
TI  - IFN type I and type II independent enhancement of B cell TLR7 expression by
      natural killer cells.
AB  - The PRR TLR7 plays a key role in the activation of autoantigen-reactive B cells.
      This response is increased markedly by IFN-alpha, produced by accessory cells, as
      a result of the up-regulation of TLR7. We report herein an alternative pathway by
      which TLR7 expression can be augmented. This finding was derived from
      continuation of ongoing studies to uncover interactions between NK and B cells.
      Here, we have compared gene expression profiles by microarray analysis of B cells
      before and after their interaction with purified NK cells. The most outstanding
      alteration of genes transcribed in B cells is a significant increase in the
      expression of many members of the ISG family, among which is TLR7. Further
      analysis revealed that the enhancement of TLR7 on B cells is not mediated via
      type I or type II IFN but by another cytokine, IL-28, a type III IFN, which acts
      in concert with contact-mediated interactions with NK cells. This increased
      expression allows B cells to respond more readily upon stimulation by its ligand
      and may increase in vivo responses to other TLR7 ligands, such as autoantigens,
      prior to or jointly with stimulation by other cytokines.

PMID- 22636321
TI  - IFN-gamma-deficient mice develop IL-1-dependent cutaneous and musculoskeletal
      inflammation during experimental brucellosis.
AB  - Human brucellosis exhibits diverse pathological manifestations that can affect
      almost any organ. In particular, osteoarticular complications are the most common
      focal manifestation of brucellosis and occur in 40-80% of patients. In
      immunocompetent mice, Brucella replication is generally restricted to the spleen,
      liver, and to a lesser extent, LNs, thereby limiting their use for study of focal
      inflammation often found in brucellosis. Here, we report that nasal, oral, or
      peritoneal infection of IFN-gamma(-/-) mice with WT Brucella melitensis or
      Brucella abortus results in joint and periarticular tissue inflammation.
      Histological analysis of the affected joints revealed inflammatory infiltrates
      and debris within the joint space colocalizing with Brucella antigen.
      Osteoarthritis, necrosis, periarticular soft tissue inflammation, and substantial
      brucellae burdens were observed. Oral rifampicin was effective in clearing
      infection and halting further progression of focal inflammation from infected IFN
      gamma(-/-) mice, although some symptoms and swelling remained. Elevated IL-1
      beta, but not TNF-alpha, IL-6, or IL-17, was detected in joint homogenates from
      infected IFN-gamma(-/-) mice. Whereas more susceptible to systemic infection, IL
      1R(-/-) mice depleted of IFN-gamma were more resistant to focal inflammation than
      WT mice similarly depleted of IFN-gamma. Collectively, these results show IFN
      gamma(-/-) mice represent a potential model for study of focal inflammation
      attributed to Brucella infection and will allow evaluation of intervention
      strategies targeting IL-1, IL-1R, or other inflammatory mediators, with the
      potential to complement antibiotic-based therapies.

PMID- 22636383
TI  - Investigation of acute knee injury.

PMID- 22636603
TI  - Indication for CDKN2A-mutation analysis in familial pancreatic cancer families
      without melanomas.
AB  - BACKGROUND: CDKN2A-mutation carriers run a high risk of developing melanomas and
      have an increased risk of developing pancreatic cancer (PC). Familial PC (FPC)
      patients with a personal history or family history of melanomas are therefore
      offered CDKN2A-mutation analysis. In contrast, CDKN2A testing in FPC families
      without a history of melanomas is not generally recommended. The aim of this
      study was to evaluate the frequency of CDKN2A-mutations in FPC families without
      melanomas. METHODS: Data were gathered from PC family registers. FPC families
      were defined as families with clustering of PC without meeting diagnostic
      criteria of familial cutaneous malignant melanoma (familial CMM) or other
      inherited cancer syndromes. Blood samples were obtained for DNA isolation from PC
      patients or first degree relatives and analysed for CDKN2A-mutations. RESULTS:
      Among 40 FPC families, DNA analyses were carried out in 28 families (70%),
      leading to identification of CDKN2A-mutations in six families (21%). None of the
      CDKN2A-mutation-positive families fulfilled the diagnostic criteria for familial
      CMM and in three CDKN2A families no melanomas were observed. Two CDKN2A-mutations
      were found; the Dutch founder mutation p16-Leiden (c.225_243del, p.Ala76fs) and
      the c.19_23dup, p.Ser8fs-mutation. After disclosure of the CDKN2A-mutation in one
      of the families, a curable melanoma was diagnosed at dermatological surveillance
      in a 17-year-old family member. CONCLUSION: CDKN2A-mutation can be found in a
      considerable proportion of families with FPC. CDKN2A-mutation analysis should
      therefore be included in genetic testing in FPC families, even in the absence of
      reported melanomas. This strategy will enhance the recognition of individuals at
      risk for PC and facilitate the early detection of melanomas.

PMID- 22636422
TI  - High yield expression and purification of recombinant human apolipoprotein A-II
      in Escherichia coli.
AB  - Recombinant expression systems have become powerful tools for understanding the
      structure and function of proteins, including the apolipoproteins that comprise
      human HDL. However, human apolipoprotein (apo)A-II has proven difficult to
      produce by recombinant techniques, likely contributing to our lack of knowledge
      about its structure, specific biological function, and role in cardiovascular
      disease. Here we present a novel Escherichia coli-based recombinant expression
      system that produces highly pure mature human apoA-II at substantial yields. A
      Mxe GyrA intein containing a chitin binding domain was fused at the C terminus of
      apoA-II. A 6* histidine-tag was also added at the fusion protein's C terminus.
      After rapid purification on a chitin column, intein auto-cleavage was induced
      under reducing conditions, releasing a peptide with only one extra N-terminal Met
      compared with the sequence of human mature apoA-II. A pass through a nickel
      chelating column removed any histidine-tagged residual fusion protein, leaving
      highly pure apoA-II. A variety of electrophoretic, mass spectrometric, and
      spectrophotometric analyses demonstrated that the recombinant form is comparable
      in structure to human plasma apoA-II. Similarly, recombinant apoA-II is
      comparable to the plasma form in its ability to bind and reorganize lipid and
      promote cholesterol efflux from macrophages via the ATP binding cassette
      transporter A1. This system is ideal for producing large quantities of
      recombinant wild-type or mutant apoA-II for structural or functional studies.

PMID- 22636604
TI  - Further delineation of the phenotype of chromosome 14q13 deletions: (positional)
      involvement of FOXG1 appears the main determinant of phenotype severity, with no
      evidence for a holoprosencephaly locus.
AB  - BACKGROUND: Deletions including chromosome 14 band q13 have been linked to
      variable phenotypes. With current molecular methods the authors aim to elucidate
      a genotype-phenotype correlation by accurately determining the size and location
      of the deletions and the associated phenotype. METHODS: Here the authors report
      the molecular karyotyping and phenotypic description of seven patients with
      overlapping deletions including chromosome 14q13. RESULTS: The authors show that
      deletions including 14q13 result in a recognisable phenotype mainly due to
      haploinsufficiency of two genes (NKX2-1, PAX9). FOXG1 (on chromosome band 14q12)
      involvement seems to be the main determinant of phenotype severity. The patients
      in this study without FOXG1 involvement and deletions of up to 10 Mb have a
      relatively mild phenotype. The authors cannot explain why some patients in
      literature with overlapping but smaller deletions appear to have a more severe
      phenotype. A previously presumed association with holoprosencephaly could not be
      confirmed as none of the patients in this series had holoprosencephaly.
      CONCLUSIONS: FOXG1 appears the main determinant of the severity of phenotypes
      resulting from deletions including 14q13. The collected data show no evidence for
      a locus for holoprosencephaly in the 14q13 region, but a locus for agenesis of
      the corpus callosum cannot be excluded.

PMID- 22636675
TI  - The continuing evolution of the Langendorff and ejecting murine heart: new
      advances in cardiac phenotyping.
AB  - The isolated retrograde-perfused Langendorff heart and the isolated ejecting
      heart have, over many decades, resulted in fundamental discoveries that form the
      underpinnings of our current understanding of the biology and physiology of the
      heart. These two experimental methodologies have proven invaluable in studying
      pharmacological effects on myocardial function, metabolism, and vascular
      reactivity and in the investigation of clinically relevant disease states such as
      ischemia-reperfusion injury, diabetes, obesity, and heart failure. With the
      advent of the genomics era, the isolated mouse heart preparation has gained
      prominence as an ex vivo research tool for investigators studying the impact of
      gene modification in the intact heart. This review summarizes the historical
      development of the isolated heart and provides a practical guide for the
      establishment of the Langendorff and ejecting heart preparations with a
      particular emphasis on the murine heart. In addition, current applications and
      novel methods of recording cardiovascular parameters in the isolated heart
      preparation will be discussed. With continued advances in methodological
      recordings, the isolated mouse heart preparation will remain physiologically
      relevant for the foreseeable future, serving as an integral bridge between in
      vitro assays and in vivo approaches.

PMID- 22636676
TI  - Protein kinase D increases maximal Ca2+-activated tension of cardiomyocyte
      contraction by phosphorylation of cMyBP-C-Ser315.
AB  - Cardiac myosin-binding protein C (cMyBP-C) is involved in the regulation of
      cardiac myofilament contraction. Recent evidence showed that protein kinase D
      (PKD) is one of the kinases that phosphorylate cMyBP-C. However, the mechanism by
      which PKD-induced cMyBP-C phosphorylation affects cardiac contractile responses
      is not known. Using immunoprecipitation, we showed that, in contracting
      cardiomyocytes, PKD binds to cMyBP-C and phosphorylates it at Ser(315). The
      effect of PKD-mediated phosphorylation of cMyBP-C on cardiac myofilament function
      was investigated in permeabilized ventricular myocytes, isolated from wild-type
      (WT) and from cMyBP-C knockout (KO) mice, incubated in the presence of full
      length active PKD. In WT myocytes, PKD increased both myofilament Ca(2+)
      sensitivity (pCa(50)) and maximal Ca(2+)-activated tension of contraction
      (T(max)). In cMyBP-C KO skinned myocytes, PKD increased pCa(50) but did not alter
      T(max). This suggests that cMyBP-C is not involved in PKD-mediated sensitization
      of myofilaments to Ca(2+) but is essential for PKD-induced increase in T(max).
      Furthermore, the phosphorylation of both PKD-Ser(916) and cMyBP-C-Ser(315) was
      contraction frequency-dependent, suggesting that PKD-mediated cMyBP-C
      phosphorylation is operational primarily during periods of increased contractile
      activity. Thus, during high contraction frequency, PKD facilitates contraction of
      cardiomyocytes by increasing Ca(2+) sensitivity and by an increased T(max)
      through phosphorylation of cMyBP-C.

PMID- 22636674
TI  - Angiotensin II enhances AT1-Nox1 binding and stimulates arterial smooth muscle
      cell migration and proliferation through AT1, Nox1, and interleukin-18.
AB  - The redox-sensitive transcription factors NF-kappaB and activator protein-1 (AP
      1) are critical mediators of ANG II signaling. The promitogenic and promigratory
      factor interleukin (IL)-18 is an NF-kappaB- and AP-1-responsive gene. Therefore,
      we investigated whether ANG II-mediated smooth muscle cell (SMC) migration and
      proliferation involve IL-18. ANG II induced rat carotid artery SMC migration and
      proliferation and IL-18 and metalloproteinase (MMP)-9 expression via ANG II type
      1 (AT(1)) receptor. ANG II-induced superoxide generation, NF-kappaB and AP-1
      activation, and IL-18 and MMP-9 induction were all markedly attenuated by
      losartan, diphenyleneiodonium chloride (DPI), and Nox1 knockdown. Similar to ANG
      II, addition of IL-18 also induced superoxide generation, activated NF-kappaB and
      AP-1, and stimulated SMC migration and proliferation, in part via Nox1, and both
      ANG II and IL-18 induced NOX1 transcription in an AP-1-dependent manner. AT(1)
      physically associates with Nox1 in SMC, and ANG II enhanced this binding.
      Interestingly, exogenous IL-18 neither induced AT(1) binding to Nox1 nor enhanced
      the ANG II-induced increase in AT(1)/Nox1 binding. Importantly, IL-18 knockdown,
      or pretreatment with IL-18 neutralizing antibodies, or IL-18 binding protein, all
      attenuated the migratory and mitogenic effects of ANG II. Continuous infusion of
      ANG II for 7 days induced carotid artery hyperplasia in rats via AT(1) and was
      associated with increased AT(1)/Nox1 binding (despite lower AT(1) levels);
      increased DPI-inhibitable superoxide production; increased phospho-IKKbeta, JNK,
      p65, and c-Jun; and induction of IL-18 and MMP-9 in endothelium-denuded carotid
      arteries. These results indicate that IL-18 amplifies the ANG II-induced, redox
      dependent inflammatory cascades by activating similar promitogenic and
      promigratory signal transduction pathways. The ANG II/Nox1/IL-18 pathway may be
      critical in hyperplastic vascular diseases, including atherosclerosis and
      restenosis.

PMID- 22636678
TI  - Interventricular heterogeneity as a substrate for arrhythmogenesis of decoupled
      mitochondria during ischemia in the whole heart.
AB  - Myocardial ischemia results in metabolic changes, which collapse the
      mitochondrial network, that increase the vulnerability of the heart to
      ventricular fibrillation (VF). It has been demonstrated at the single cell level
      that uncoupling the mitochondria using carbonyl cyanide p-(tri
      fluoromethoxy)phenyl-hydrazone (FCCP) at low concentrations can be
      cardioprotective. The aim of our study was to investigate the effect of FCCP on
      arrhythmogenesis during ischemia in the whole rabbit heart. We performed optical
      mapping of isolated rabbit hearts (n = 33) during control and 20 min of global
      ischemia and reperfusion, both with and without pretreatment with the
      mitochondrial uncoupler FCCP at 100, 50, or 30 nM. No hearts went into VF during
      ischemia under the control condition, with or without the electromechanical
      uncoupler blebbistatin. We found that pretreatment with 100 (n = 4) and 50 (n =
      6) nM FCCP, with or without blebbistatin, leads to VF during ischemia in all
      hearts, whereas pretreatment with 30 nM of FCCP led to three out of eight hearts
      going into VF during ischemia. We demonstrated that 30 nM of FCCP significantly
      increased interventricular (but not intraventricular) action potential duration
      and conduction velocity heterogeneity in the heart during ischemia, thus
      providing the substrate for VF. We showed that wavebreaks during VF occurred
      between the right and left ventricular junction. We also demonstrated that no VF
      occurred in the heart pretreated with 10 MUM glibenclamide, which is known to
      abolish interventricular heterogeneity. Our results indicate that low
      concentrations of FCCP, although cardioprotective at the single cell level, are
      arrhythmogenic at the whole heart level. This is due to the fact that FCCP
      induces different electrophysiological changes to the right and left ventricle,
      thus increasing interventricular heterogeneity and providing the substrate for
      VF.

PMID- 22636677
TI  - Increased hemoglobin O2 affinity protects during acute hypoxia.
AB  - Acclimatization to hypoxia requires time to complete the adaptation mechanisms
      that influence oxygen (O(2)) transport and O(2) utilization. Although decreasing
      hemoglobin (Hb) O(2) affinity would favor the release of O(2) to the tissues,
      increasing Hb O(2) affinity would augment arterial O(2) saturation during
      hypoxia. This study was designed to test the hypothesis that pharmacologically
      increasing the Hb O(2) affinity will augment O(2) transport during severe hypoxia
      (10 and 5% inspired O(2)) compared with normal Hb O(2) affinity. RBC Hb O(2)
      affinity was increased by infusion of 20 mg/kg of 5-hydroxymethyl-2-furfural
      (5HMF). Control animals received only the vehicle. The effects of increasing Hb
      O(2) affinity were studied in the hamster window chamber model, in terms of
      systemic and microvascular hemodynamics and partial pressures of O(2) (Po(2)).
      Pimonidazole binding to hypoxic areas of mice heart and brain was also studied.
      5HMF decreased the Po(2) at which the Hb is 50% saturated with O(2) by 12.6 mmHg.
      During 10 and 5% O(2) hypoxia, 5HMF increased arterial blood O(2) saturation by
      35 and 48% from the vehicle group, respectively. During 5% O(2) hypoxia, blood
      pressure and heart rate were 58 and 30% higher for 5HMF compared with the
      vehicle. In addition, 5HMF preserved microvascular blood flow, whereas blood flow
      decreased to 40% of baseline in the vehicle group. Consequently, perivascular
      Po(2) was three times higher in the 5HMF group compared with the control group at
      5% O(2) hypoxia. 5HMF also reduced heart and brain hypoxic areas in mice.
      Therefore, increased Hb O(2) affinity resulted in hemodynamics and oxygenation
      benefits during severe hypoxia. This acute acclimatization process may have
      implications in survival during severe environmental hypoxia when logistic
      constraints prevent chronic acclimatization.

PMID- 22636679
TI  - Blockade of ATP-sensitive potassium channels prevents the attenuation of the
      exercise pressor reflex by tempol in rats with ligated femoral arteries.
AB  - We reported previously that tempol attenuated the exercise pressor and muscle
      mechanoreceptor reflexes in rats whose femoral arteries were ligated, whereas
      tempol did not attenuate these reflexes in rats whose femoral arteries were
      freely perfused. Although the mechanism whereby tempol attenuated these reflexes
      in rats whose femoral artery was ligated was independent of its ability to
      scavenge reactive oxygen species, its nature remains unclear. An alternative
      explanation for the tempol-induced attenuation of these reflexes involves ATP
      sensitive potassium channels (K(ATP)) and calcium-activated potassium channels
      (BK(Ca)), both of which are opened by tempol. We tested the likelihood of this
      explanation by measuring the effects of either glibenclamide (0.1 mg/kg), which
      blocks K(ATP) channels, or iberiotoxin (20 or 40 MUg/kg), which blocks BK(Ca)
      channels, on the tempol-induced attenuation of the exercise pressor and muscle
      mechanoreceptor reflexes in decerebrated rats whose femoral arteries were
      ligated. We found that glibenclamide prevented the tempol-induced attenuation of
      both reflexes, whereas iberiotoxin did not. We also found that the amount of
      protein comprising the pore of the K(ATP) channel in the dorsal root ganglia
      innervating hindlimbs whose femoral artery was ligated was significantly greater
      than that in the dorsal root ganglia innervating hindlimbs whose femoral arteries
      were freely perfused. In contrast, the amounts of protein comprising the BK(Ca)
      channel in the dorsal root ganglia innervating the ligated and freely perfused
      hindlimbs were not different. We conclude that tempol attenuated both reflexes by
      opening K(ATP) channels, an effect that hyperpolarized muscle afferents
      stimulated by static contraction or tendon stretch.

PMID- 22636680
TI  - MRI-based prediction of adverse cardiac remodeling after murine myocardial
      infarction.
AB  - Myocardial infarction (MI) results in adverse cardiac remodeling leading to heart
      failure and increased mortality. Experimental mouse models of MI are extensively
      used to identify mechanisms underlying adverse remodeling, but the extent of
      remodeling that occurs may be highly variable and can limit the utility to
      discover new disease pathways. The ability to predict the development of
      significant late post-MI remodeling would be invaluable in conducting such
      studies by increasing throughput and efficiency. This study aimed to identify
      potential thresholds of cardiac magnetic resonance imaging (MRI) parameters
      measured early after murine MI that would predict the development of significant
      adverse remodeling at 4 wk. MI was achieved by permanent coronary ligation and
      animals (n = 84) were followed up for 4 wk subsequently. MRI was used to assess
      left ventricular (LV) volumes, mass and ejection fraction, as well as infarct
      size (IS). Late gadolinium enhancement cine-MRI was performed at 2 days with
      standard cine-MRI at 30 days post-MI. Utilizing multiple logistic regression, we
      found that IS >36%, at 2 days post-MI, was the overall best single predictor of
      adverse remodeling at 30 days (sensitivity 80.7%, specificity 88.9%; C-statistic
      of 0.939 from receiver-operating curve analysis). LV end-systolic volume (LVESV)
      >32 MUl was also an excellent predictor comparable to IS. The combination of IS
      >36% and/or LVESV >32 MUl provided the highest predictive values for late adverse
      remodeling among multiple predictors. This study demonstrates that MRI-based
      estimation of IS and ESV during the acute phase of murine MI are good predictors
      of subsequent adverse remodeling that may aid experimental design.

PMID- 22636681
TI  - Mitofusins and the mitochondrial permeability transition: the potential downside
      of mitochondrial fusion.
AB  - Mitofusins (Mfn-1 and Mfn-2) are transmembrane proteins that bind and hydrolyze
      guanosine 5'-triphosphate to bring about the merging of adjacent mitochondrial
      membranes. This event is necessary for mitochondrial fusion, a biological process
      that is critical for organelle function. The broad effects of mitochondrial
      fusion on cell bioenergetics have been extensively studied, whereas the local
      effects of mitofusin activity on the structure and integrity of the fusing
      mitochondrial membranes have received relatively little attention. From the study
      of fusogenic proteins, theoretical models, and simulations, it has been noted
      that the fusion of biological membranes is associated with local perturbations on
      the integrity of the membrane that present in the form of lipidic holes which
      open on the opposing bilayers. These lipidic holes represent obligate
      intermediates that make the fusion process thermodynamically more favorable and
      at the same time induce leakage to the fusing membranes. In this perspectives
      article we present the relevant evidence selected from a spectrum of membrane
      fusion/leakage models and attempt to couple this information with observations
      conducted with cardiac myocytes or mitochondria deficient in Mfn-1 and Mfn-2.
      More specifically, we argue in favor of a situation whereby mitochondrial fusion
      in cardiac myocytes is coupled with outer mitochondrial membrane destabilization
      that is opportunistically employed during the process of mitochondrial
      permeability transition. We hope that these insights will initiate research on
      this new hypothesis of mitochondrial permeability transition regulation, a poorly
      understood mitochondrial function with significant consequences on myocyte
      survival.

PMID- 22636682
TI  - Cell-based therapy for prevention and reversal of myocardial remodeling.
AB  - Although pharmacological and interventional advances have reduced the morbidity
      and mortality of ischemic heart disease, there is an ongoing need for novel
      therapeutic strategies that prevent or reverse progressive ventricular remodeling
      following myocardial infarction, the process that forms the substrate for
      ventricular failure. The development of cell-based therapy as a strategy to
      repair or regenerate injured tissue offers extraordinary promise for a powerful
      anti-remodeling therapy. In this regard, the field of cell therapy has made major
      advancements in the past decade. Accumulating data from preclinical studies have
      provided novel insights into stem cell engraftment, differentiation, and
      interactions with host cellular elements, as well as the effectiveness of various
      methods of cell delivery and accuracy of diverse imaging modalities to assess
      therapeutic efficacy. These findings have in turn guided rationally designed
      translational clinical investigations. Collectively, there is a growing
      understanding of the parameters that underlie successful cell-based approaches
      for improving heart structure and function in ischemic and other
      cardiomyopathies.

PMID- 22636767
TI  - FeoB2 Functions in magnetosome formation and oxidative stress protection in
      Magnetospirillum gryphiswaldense strain MSR-1.
AB  - Magnetotactic bacteria (MTB) synthesize unique organelles, the magnetosomes,
      which are intracellular nanometer-sized, membrane-enveloped magnetite. The
      biomineralization of magnetosomes involves the uptake of large amounts of iron.
      However, the iron metabolism of MTB is not well understood. The genome of the
      magnetotactic bacterium Magnetospirillum gryphiswaldense strain MSR-1 contains
      two ferrous iron transport genes, feoB1 and feoB2. The FeoB1 protein was reported
      to be responsible mainly for the transport of ferrous iron and to play an
      accessory role in magnetosome formation. To determine the role of feoB2, we
      constructed an feoB2 deletion mutant (MSR-1 DeltafeoB2) and an feoB1 feoB2 double
      deletion mutant (MSR-1 NfeoB). The single feoB2 mutation did not affect magnetite
      crystal biomineralization. MSR-1 NfeoB had a significantly lower average
      magnetosome number per cell (~65%) than MSR-1 DeltafeoB1, indicating that FeoB2
      plays a role in magnetosome formation when the feoB1 gene is deleted. Our
      findings showed that FeoB1 has a greater ferrous iron transport ability than
      FeoB2 and revealed the differential roles of FeoB1 and FeoB2 in MSR-1 iron
      metabolism. Interestingly, compared to the wild type, the feoB mutants showed
      increased sensitivity to oxidative stress and lower activities of the enzymes
      superoxide dismutase and catalase, indicating that the FeoB proteins help protect
      bacterial cells from oxidative stress.

PMID- 22636768
TI  - Growth phase-dependent modulation of Rgg binding specificity in Streptococcus
      pyogenes.
AB  - Streptococcus pyogenes Rgg is a transcriptional regulator that interacts with the
      cofactor LacD.1 to control growth phase-dependent expression of genes, including
      speB, which encodes a secreted cysteine protease. LacD.1 is thought to interact
      with Rgg when glycolytic intermediates are abundant in a manner that prevents Rgg
      mediated activation of speB expression via binding to the promoter region. When
      the intermediates diminish, LacD.1 dissociates from Rgg and binds to the speB
      promoter to activate expression. The purpose of this study was to determine if
      Rgg bound to chromatin during the exponential phase of growth and, if so, to
      identify the binding sites. Rgg bound to 62 chromosomal sites, as determined by
      chromatin immunoprecipitation coupled with DNA microarrays. Thirty-eight were
      within noncoding DNA, including sites upstream of the genes encoding the M
      protein (M49), serum opacity factor (SOF), fibronectin-binding protein (SfbX49),
      and a prophage-encoded superantigen, SpeH. Each of these sites contained a
      promoter that was regulated by Rgg, as determined with transcriptional fusion
      assays. Purified Rgg also bound to the promoter regions of emm49, sof, and sfbX49
      in vitro. Results obtained with a lacD.1 mutant showed that both LacD.1 and Rgg
      were necessary for the repression of emm49, sof, sfbX49, and speH expression.
      Overall, the results indicated that the DNA binding specificity of Rgg is
      responsive to environmental changes in a LacD.1-dependent manner and that Rgg and
      LacD.1 directly control virulence gene expression in the exponential phase of
      growth.

PMID- 22636769
TI  - Enterococcus faecalis PrgJ, a VirB4-like ATPase, mediates pCF10 conjugative
      transfer through substrate binding.
AB  - The Enterococcus faecalis prg and pcf genes of plasmid pCF10 encode a type IV
      secretion system (T4SS) required for conjugative transfer. PrgJ is a member of
      the VirB4 family of ATPases that are universally associated with T4SSs. Here, we
      report that purified PrgJ dimers displayed ATP binding and hydrolysis activities.
      A PrgJ nucleoside triphosphate (NTP) binding site mutation (K471E) slightly
      diminished ATP binding but abolished ATP hydrolysis in vitro and blocked pCF10
      transfer in vivo. As shown with affinity pulldown assays, PrgJ and the K471E
      mutant protein interacted with the substrate receptor PcfC and with relaxase PcfG
      and accessory factor PcfF, which together form the relaxosome at the oriT
      sequence to initiate plasmid processing. The purified PrgJ and K471E proteins
      also bound single- and double-stranded DNA substrates without sequence
      specificity in vitro, and both PrgJ derivatives bound pCF10 in vivo by a
      mechanism dependent on an intact oriT sequence and cosynthesis of PcfC, PcfF, and
      PcfG, as shown by a formaldehyde-cross-linking assay. Our findings support a
      model in which the PcfC receptor coordinates with the PrgJ ATPase to drive early
      steps of pCF10 processing/transfer: (i) PcfC first binds the pCF10 relaxosome
      through contacts with PcfF, PcfG, and DNA; (ii) PcfC delivers the plasmid
      substrate to PrgJ; and (iii) PrgJ catalyzes substrate transfer to the membrane
      translocase. Substrate engagement with a VirB4-like subunit has not been
      previously described; consequently, our studies point to a novel function for
      these signature T4SS ATPases in mediating early steps of type IV secretion.

PMID- 22636770
TI  - Cellular characterization of the primosome and rep helicase in processing and
      restoration of replication following arrest by UV-induced DNA damage in
      Escherichia coli.
AB  - Following arrest by UV-induced DNA damage, replication is restored through a
      sequence of steps that involve partial resection of the nascent DNA by RecJ and
      RecQ, branch migration and processing of the fork DNA surrounding the lesion by
      RecA and RecF-O-R, and resumption of DNA synthesis once the blocking lesion has
      been repaired or bypassed. In vitro, the primosomal proteins (PriA, PriB, and
      PriC) and Rep are capable of initiating replication from synthetic DNA fork
      structures, and they have been proposed to catalyze these events when replication
      is disrupted by certain impediments in vivo. Here, we characterized the role that
      PriA, PriB, PriC, and Rep have in processing and restoring replication forks
      following arrest by UV-induced DNA damage. We show that the partial degradation
      and processing of the arrested replication fork occurs normally in both rep and
      primosome mutants. In each mutant, the nascent degradation ceases and DNA
      synthesis initially resumes in a timely manner, but the recovery then stalls in
      the absence of PriA, PriB, or Rep. The results demonstrate a role for the
      primosome and Rep helicase in overcoming replication forks arrested by UV-induced
      damage in vivo and suggest that these proteins are required for the stability and
      efficiency of the replisome when DNA synthesis resumes but not to initiate de
      novo replication downstream of the lesion.

PMID- 22636771
TI  - Novel L-cysteine-dependent maleylpyruvate isomerase in the gentisate pathway of
      Paenibacillus sp. strain NyZ101.
AB  - Glutathione- and mycothiol-dependent maleylpyruvate isomerases are known to be
      involved, respectively, in gentisate catabolism in Gram-negative and high G+C
      Gram-positive strains. In the present study, a low-G+C Gram-positive
      Paenibacillus sp. strain, NyZ101, was isolated and shown to degrade 3
      hydroxybenzoate via gentisate. A 6.5-kb fragment containing a conserved region of
      gentisate 1,2-dioxygenase genes was cloned and sequenced, and four genes
      (bagKLIX) were shown to encode the enzymes involved in the catabolism to central
      metabolites of 3-hydroxybenzoate via gentisate. The Bag proteins share moderate
      identities with the reported enzymes in the 3-hydroxybenzoate catabolism, except
      BagL that had no obvious homology with any functionally characterized proteins.
      Recombinant BagL was purified to homogeneity as a His-tagged protein and likely a
      dimer by gel filtration. BagL was demonstrated to be a novel thiol-dependent
      maleylpyruvate isomerase catalyzing the isomerization of maleylpyruvate to
      fumarylpyruvate with L-cysteine, cysteinylglycine, or glutathione, as its
      cofactor. The K(m) values of these three thiols for BagL were 15.5, 8.4, and 552
      MUM, respectively. Since cysteine and coenzyme A were reported to be abundant in
      low-G+C Gram-positive strains, BagL should utilize L-cysteine as its
      physiological cofactor in vivo. The addition of Ni(2+) increased BagL activity,
      and site-directed mutagenesis experiments indicated that three conserved
      histidines in BagL were associated with binding to Ni(2+) ion and were necessary
      for its enzyme activity. BagL is the first characterized L-cysteine-dependent
      catabolic enzyme in microbial metabolism and is likely a new and distinct member
      of DinB family, with a four-helix-bundle topology, as deduced by sequence
      analysis and homology modeling.

PMID- 22636772
TI  - Characterization of a Vibrio fischeri aminopeptidase and evidence for its
      influence on an early stage of squid colonization.
AB  - Vibrio fischeri cells are the sole colonists of a specialized light organ in the
      mantle cavity of the sepiolid squid Euprymna scolopes. The process begins when
      the bacteria aggregate in mucus secretions outside the light organ. The cells
      eventually leave the aggregate, enter the light organ, and encounter a rich
      supply of peptides. The need to dissociate from mucus and presumably utilize
      peptides led us to hypothesize that protease activity is integral to the
      colonization process. Protease activity associated with whole cells of Vibrio
      fischeri strain ES114 was identified as the product of a putative cell membrane
      associated aminopeptidase (PepN). To characterize this activity, the
      aminopeptidase was cloned, overexpressed, and purified. Initial steady-state
      kinetic studies revealed that the aminopeptidase has broad activity, with a
      preference for basic and hydrophobic side chains and k(cat) and K(m) values that
      are lower and smaller, respectively, than those of Escherichia coli PepN. A V.
      fischeri mutant unable to produce PepN is significantly delayed in its ability to
      colonize squid within the first 12 h, but eventually it establishes a wild-type
      colonization level. Likewise, in competition with the wild type for colonization,
      the mutant is outcompeted at 12 h postinoculation but then competes evenly by 24
      h. Also, the PepN-deficient strain fails to achieve wild-type levels of cells in
      aggregates, suggesting an explanation for the initial colonization delay. This
      study provides a foundation for more studies on PepN expression, localization,
      and role in the early stages of squid colonization.

PMID- 22636773
TI  - Sinorhizobium meliloti ExoR is the target of periplasmic proteolysis.
AB  - Sinorhizobium meliloti ExoR regulates the production of succinoglycan and
      flagella through the ExoS/ChvI two-component regulatory system. ExoR has been
      proposed to inhibit the ExoS sensor through direct interaction in the periplasm.
      To understand how ExoR suppression of ExoS is relieved, which is required for the
      expression of ExoS/ChvI-regulated symbiosis genes, we characterized wild-type
      ExoR and ExoR95 mutant proteins. In addition to the previously identified
      precursor and mature forms of ExoR (designated ExoR(p) and ExoR(m),
      respectively), we detected a 20-kDa form of ExoR (designated ExoR(c20)) derived
      from the wild-type ExoR protein, but not from the ExoR95 mutant protein.
      ExoR(c20) was isolated directly from S. meliloti periplasm to identify its N
      terminal amino acids and the site of the proteolysis, which is highly conserved
      among ExoR homologs. ExoR(c20) retains the C terminus of the wild-type ExoR. When
      expressed directly, ExoR(c20) did not complement the exoR95 mutation, suggesting
      that ExoR(c20) does not function directly in the ExoR-ExoS/ChvI regulatory
      pathway and that ExoR(m) is the functional form of ExoR. A single-amino-acid
      change (ExoRL81A) at the site of ExoR periplasmic proteolysis resulted in the
      reduction of the amount of ExoR(m) and the loss of the regulatory function of the
      ExoR protein. These findings suggest that ExoR(m) is a target of periplasmic
      proteolysis and that the amount of ExoR(m) could be reduced through effective
      proteolysis to relieve its suppression of ExoS.

PMID- 22636775
TI  - Role of the fused corrinoid/methyl transfer protein CmtA during CO-dependent
      growth of Methanosarcina acetivorans.
AB  - The genome of Methanosarcina acetivorans encodes three homologs, initially
      annotated as hypothetical fused corrinoid/methyl transfer proteins, which are
      highly elevated in CO-grown cells versus cells grown with alternate substrates.
      Based only on phenotypic analyses of deletion mutants, it was previously
      concluded that the homologs are strictly dimethylsulfide:coenzyme M (CoM)
      methyltransferases not involved in the metabolism of CO (E. Oelgeschlager and M.
      Rother, Mol. Microbiol. 72:1260 -1272, 2009). The homolog encoded by MA4383 (here
      designated CmtA) was reexamined via biochemical characterization of the protein
      overproduced in Escherichia coli. Purified CmtA reconstituted with
      methylcob(III)alamin contained a molar ratio of cobalt to protein of 1.0 +/- 0.2.
      The UV-visible spectrum was typical of methylated corrinoid-containing proteins,
      with absorbance maxima at 370 and 420 nm and a band of broad absorbance between
      450 and 600 nm with maxima at 525, 490, and 550 nm. CmtA reconstituted with
      aquocobalamin showed methyl-tetrahydromethanopterin:CoM (CH(3)-THMPT:HS-CoM)
      methyltransferase activity (0.31 MUmol/min/mg) with apparent K(m) values of 135
      MUM for CH(3)-THMPT and 277 MUM for HS-CoM. The ratio of CH(3)-THMPT:HS-CoM
      methyltransferase activity in the soluble versus membrane cellular fractions was
      15-fold greater in CO-grown versus methanol-grown cells. A mutant strain deleted
      for the CmtA gene showed lower growth rates and final yields when cultured with
      growth-limiting partial pressures of CO, demonstrating a role for CmtA during
      growth with this substrate. The results establish that CmtA is a soluble CH(3)
      THSPT:HS-CoM methyltransferase postulated to supplement the membrane-bound CH(3)
      THMPT:HS-CoM methyltransferase during CO-dependent growth of M. acetivorans.
      Thus, we propose that the name of the enzyme encoded by MA4384 be CmtA (for
      cytoplasmic methyltransferase).

PMID- 22636774
TI  - Caldicellulosiruptor core and pangenomes reveal determinants for noncellulosomal
      thermophilic deconstruction of plant biomass.
AB  - Extremely thermophilic bacteria of the genus Caldicellulosiruptor utilize
      carbohydrate components of plant cell walls, including cellulose and
      hemicellulose, facilitated by a diverse set of glycoside hydrolases (GHs). From a
      biofuel perspective, this capability is crucial for deconstruction of plant
      biomass into fermentable sugars. While all species from the genus grow on xylan
      and acid-pretreated switchgrass, growth on crystalline cellulose is variable. The
      basis for this variability was examined using microbiological, genomic, and
      proteomic analyses of eight globally diverse Caldicellulosiruptor species. The
      open Caldicellulosiruptor pangenome (4,009 open reading frames [ORFs]) encodes
      106 GHs, representing 43 GH families, but only 26 GHs from 17 families are
      included in the core (noncellulosic) genome (1,543 ORFs). Differentiating the
      strongly cellulolytic Caldicellulosiruptor species from the others is a specific
      genomic locus that encodes multidomain cellulases from GH families 9 and 48,
      which are associated with cellulose-binding modules. This locus also encodes a
      novel adhesin associated with type IV pili, which was identified in the
      exoproteome bound to crystalline cellulose. Taking into account the core genomes,
      pangenomes, and individual genomes, the ancestral Caldicellulosiruptor was likely
      cellulolytic and evolved, in some cases, into species that lost the ability to
      degrade crystalline cellulose while maintaining the capacity to hydrolyze
      amorphous cellulose and hemicellulose.

PMID- 22636776
TI  - Pathway and enzyme redundancy in putrescine catabolism in Escherichia coli.
AB  - Putrescine as the sole carbon source requires a novel catabolic pathway with
      glutamylated intermediates. Nitrogen limitation does not induce genes of this
      glutamylated putrescine (GP) pathway but instead induces genes for a putrescine
      catabolic pathway that starts with a transaminase-dependent deamination. We
      determined pathway utilization with putrescine as the sole nitrogen source by
      examining mutants with defects in both pathways. Blocks in both the GP and
      transaminase pathways were required to prevent growth with putrescine as the sole
      nitrogen source. Genetic and biochemical analyses showed redundant enzymes for
      gamma-aminobutyraldehyde dehydrogenase (PatD/YdcW and PuuC), gamma-aminobutyrate
      transaminase (GabT and PuuE), and succinic semialdehyde dehydrogenase (GabD and
      PuuC). PuuC is a nonspecific aldehyde dehydrogenase that oxidizes all the
      aldehydes in putrescine catabolism. A puuP mutant failed to use putrescine as the
      nitrogen source, which implies one major transporter for putrescine as the sole
      nitrogen source. Analysis of regulation of the GP pathway shows induction by
      putrescine and not by a product of putrescine catabolism and shows that
      putrescine accumulates in puuA, puuB, and puuC mutants but not in any other
      mutant. We conclude that two independent sets of enzymes can completely degrade
      putrescine to succinate and that their relative importance depends on the
      environment.

PMID- 22636777
TI  - FdhTU-modulated formate dehydrogenase expression and electron donor availability
      enhance recovery of Campylobacter jejuni following host cell infection.
AB  - Campylobacter jejuni is a food-borne bacterial pathogen that colonizes the
      intestinal tract and causes severe gastroenteritis. Interaction with host
      epithelial cells is thought to enhance severity of disease, and the ability of C.
      jejuni to modulate its metabolism in different in vivo and environmental niches
      contributes to its success as a pathogen. A C. jejuni operon comprising two genes
      that we designated fdhT (CJJ81176_1492) and fdhU (CJJ81176_1493) is conserved in
      many bacterial species. Deletion of fdhT or fdhU in C. jejuni resulted in
      apparent defects in adherence and/or invasion of Caco-2 epithelial cells when
      assessed by CFU enumeration on standard Mueller-Hinton agar. However,
      fluorescence microscopy indicated that each mutant invaded cells at wild-type
      levels, instead suggesting roles for FdhTU in either intracellular survival or
      postinvasion recovery. The loss of fdhU caused reduced mRNA levels of formate
      dehydrogenase (FDH) genes and a severe defect in FDH activity. Cell infection
      phenotypes of a mutant deleted for the FdhA subunit of FDH and an DeltafdhU
      DeltafdhA double mutant were similar to those of a DeltafdhU mutant, which
      likewise suggested that FdhU and FdhA function in the same pathway. Cell
      infection assays followed by CFU enumeration on plates supplemented with sodium
      sulfite abolished the DeltafdhU and DeltafdhA mutant defects and resulted in
      significantly enhanced recovery of all strains, including wild type, at the
      invasion and intracellular survival time points. Collectively, our data indicate
      that FdhTU and FDH are required for optimal recovery following cell infection and
      suggest that C. jejuni alters its metabolic potential in the intracellular
      environment.

PMID- 22636778
TI  - cis-Acting elements that control expression of the master virulence regulatory
      gene atxA in Bacillus anthracis.
AB  - Transcription of the Bacillus anthracis structural genes for the anthrax toxin
      proteins and biosynthetic operon for capsule is positively regulated by AtxA, a
      transcription regulator with unique properties. Consistent with the role of atxA
      in virulence factor expression, a B. anthracis atxA-null mutant is avirulent in a
      murine model for anthrax. In culture, multiple signals impact atxA transcript
      levels, and the timing and steady-state level of atxA expression are critical for
      optimal toxin and capsule synthesis. Despite the apparent complex control of atxA
      transcription, only one trans-acting protein, the transition state regulator
      AbrB, has been demonstrated to interact directly with the atxA promoter. Here we
      employ 5' and 3' deletion analysis and site-directed mutagenesis of the atxA
      control region to demonstrate that atxA transcription from the major start site
      P1 is dependent upon a consensus sequence for the housekeeping sigma factor SigA
      and an A+T-rich upstream element for RNA polymerase. We also show that an
      additional trans-acting protein(s) binds specifically to atxA promoter sequences
      located between -13 and +36 relative to P1 and negatively impacts transcription.
      Deletion of this region increases promoter activity up to 15-fold. Site-directed
      mutagenesis of a 9-bp palindromic sequence within the region prevents binding of
      the trans-acting protein(s), increasing promoter activity 7-fold and resulting in
      a corresponding increase in AtxA and anthrax toxin production. Notably, an atxA
      promoter mutant that produced elevated levels of AtxA and toxin proteins during
      culture was unaffected for virulence in a murine model for anthrax.

PMID- 22636779
TI  - MS_RHII-RSD, a dual-function RNase HII-(p)ppGpp synthetase from Mycobacterium
      smegmatis.
AB  - In the noninfectious soil saprophyte Mycobacterium smegmatis, intracellular
      levels of the stress alarmones guanosine tetraphosphate and guanosine
      pentaphosphate, together termed (p)ppGpp, are regulated by the enzyme Rel(Msm).
      This enzyme consists of a single, bifunctional polypeptide chain that is capable
      of both synthesizing and hydrolyzing (p)ppGpp. The rel(Msm) knockout strain of M.
      smegmatis (Deltarel(Msm)) is expected to show a (p)ppGpp null [(p)ppGpp(0)]
      phenotype. Contrary to this expectation, the strain is capable of synthesizing
      (p)ppGpp in vivo. In this study, we identify and functionally characterize the
      open reading frame (ORF), MSMEG_5849, that encodes a second functional (p)ppGpp
      synthetase in M. smegmatis. In addition to (p)ppGpp synthesis, the 567-amino-acid
      long protein encoded by this gene is capable of hydrolyzing RNA.DNA hybrids and
      bears similarity to the conventional RNase HII enzymes. We have classified this
      protein as actRel(Msm) in accordance with the recent nomenclature proposed and
      have named it MS_RHII-RSD, indicating the two enzymatic activities present [RHII,
      RNase HII domain, originally identified as domain of unknown function 429
      (DUF429), and RSD, RelA_SpoT nucleotidyl transferase domain, the SYNTH domain
      responsible for (p)ppGpp synthesis activity]. MS_RHII-RSD is expressed and is
      constitutively active in vivo and behaves like a monofunctional (p)ppGpp
      synthetase in vitro. The occurrence of the RNase HII and (p)ppGpp synthetase
      domains together on the same polypeptide chain is suggestive of an in vivo role
      for this novel protein as a link connecting the essential life processes of DNA
      replication, repair, and transcription to the highly conserved stress survival
      pathway, the stringent response.

PMID- 22636780
TI  - Genome sequencing of a genetically tractable Pyrococcus furiosus strain reveals a
      highly dynamic genome.
AB  - The model archaeon Pyrococcus furiosus grows optimally near 100 degrees C on
      carbohydrates and peptides. Its genome sequence (NCBI) was determined 12 years
      ago. A genetically tractable strain, COM1, was very recently reported, and here
      we describe its genome sequence. Of 1,909,827 bp in size, it is 1,571 bp longer
      (0.1%) than the reference NCBI sequence. The COM1 genome contains numerous
      chromosomal rearrangements, deletions, and single base changes. COM1 also has 45
      full or partial insertion sequences (ISs) compared to 35 in the reference NCBI
      strain, and these have resulted in the direct deletion or insertional
      inactivation of 13 genes. Another seven genes were affected by chromosomal
      deletions and are predicted to be nonfunctional. In addition, the amino acid
      sequences of another 102 of the 2,134 predicted gene products are different in
      COM1. These changes potentially impact various cellular functions, including
      carbohydrate, peptide, and nucleotide metabolism; DNA repair; CRISPR-associated
      defense; transcriptional regulation; membrane transport; and growth at 72 degrees
      C. For example, the IS-mediated inactivation of riboflavin synthase in COM1
      resulted in a riboflavin requirement for growth. Nevertheless, COM1 grew on
      cellobiose, malto-oligosaccharides, and peptides in complex and minimal media at
      98 and 72 degrees C to the same extent as did both its parent strain and a new
      culture collection strain (DSMZ 3638). This was in spite of COM1 lacking several
      metabolic enzymes, including nonphosphorylating glyceraldehyde-3-phosphate
      dehydrogenase and beta-glucosidase. The P. furiosus genome is therefore of high
      plasticity, and the availability of the COM1 sequence will be critical for the
      future studies of this model hyperthermophile.

PMID- 22636781
TI  - Characterization of the PIB-Type ATPases present in Thermus thermophilus.
AB  - P(IB)-type ATPases transport heavy metals (Cu(2+), Cu(+), Ag(+), Zn(2+), Cd(2+),
      Co(2+)) across biomembranes, playing a key role in homeostasis and in the
      mechanisms of biotolerance of these metals. Three genes coding for putative P(IB)
      type ATPases are present in the genome of Thermus thermophilus (HB8 and HB27):
      the TTC1358, TTC1371, and TTC0354 genes; these genes are annotated, respectively,
      as two copper transporter (CopA and CopB) genes and a zinc-cadmium transporter
      (Zn(2+)/Cd(2+)-ATPase) gene. We cloned and expressed the three proteins with 8His
      tags using a T. thermophilus expression system. After purification, each of the
      proteins was shown to have phosphodiesterase activity at 65 degrees C with ATP
      and p-nitrophenyl phosphate (pNPP) as substrates. CopA was found to have greater
      activity in the presence of Cu(+), while CopB was found to have greater activity
      in the presence of Cu(2+). The putative Zn(2+)/Cd(2+)-ATPase was truncated at the
      N terminus and was, surprisingly, activated in vitro by copper but not by zinc or
      cadmium. When expressed in Escherichia coli, however, the putative Zn(2+)/Cd(2+)
      ATPase could be isolated as a full-length protein and the ATPase activity was
      increased by the addition of Zn(2+) and Cd(2+) as well as by Cu(+). Mutant
      strains in which each of the three P-type ATPases was deleted singly were
      constructed. In each case, the deletion increased the sensitivity of the strain
      to growth in the presence of copper in the medium, indicating that each of the
      three can pump copper out of the cells and play a role in copper detoxification.

PMID- 22636782
TI  - Bacterium-generated nitric oxide hijacks host tumor necrosis factor alpha
      signaling and modulates the host cell cycle in vitro.
AB  - In mammalian cells, nitric oxide (NO.) is an important signal molecule with
      concentration-dependent and often controversial functions of promoting cell
      survival and inducing cell death. An inducible nitric oxide synthase (iNOS) in
      various mammalian cells produces higher levels of NO. from l-arginine upon
      infections to eliminate pathogens. In this study, we reveal novel pathogenic
      roles of NO. generated by bacteria in bacterium-host cell cocultures using
      Moraxella catarrhalis, a respiratory tract disease-causing bacterium, as a
      biological producer of NO.. We recently demonstrated that M. catarrhalis cells
      that express the nitrite reductase (AniA protein) can produce NO. by reducing
      nitrite. Our study suggests that, in the presence of pathophysiological levels of
      nitrite, this opportunistic pathogen hijacks host cell signaling and modulates
      host gene expression through its ability to produce NO. from nitrite. Bacterium
      generated NO. significantly increases the secretion of tumor necrosis factor
      alpha (TNF-alpha) and modulates the expression of apoptotic proteins, therefore
      triggering host cell programmed death partially through TNF-alpha signaling.
      Furthermore, our study reveals that bacterium-generated NO. stalls host cell
      division and directly results in the death of dividing cells by reducing the
      levels of an essential regulator of cell division. This study provides unique
      insight into why NO. may exert more severe cytotoxic effects on fast growing
      cells, providing an important molecular basis for NO.-mediated pathogenesis in
      infections and possible therapeutic applications of NO.-releasing molecules in
      tumorigenesis. This study strongly suggests that bacterium-generated NO. can play
      important pathogenic roles during infections.

PMID- 22636783
TI  - The bhuQ gene encodes a heme oxygenase that contributes to the ability of
      Brucella abortus 2308 to use heme as an iron source and is regulated by Irr.
AB  - The Brucella BhuQ protein is a homolog of the Bradyrhizobium japonicum heme
      oxygenases HmuD and HmuQ. To determine if this protein plays a role in the
      ability of Brucella abortus 2308 to use heme as an iron source, an isogenic bhuQ
      mutant was constructed and its phenotype evaluated. Although the Brucella abortus
      bhuQ mutant DCO1 did not exhibit a defect in its capacity to use heme as an iron
      source or evidence of increased heme toxicity in vitro, this mutant produced
      increased levels of siderophore in response to iron deprivation compared to 2308.
      Introduction of a bhuQ mutation into the B. abortus dhbC mutant BHB2 (which
      cannot produce siderophores) resulted in a severe growth defect in the dhbC bhuQ
      double mutant JFO1 during cultivation under iron-restricted conditions, which
      could be rescued by the addition of FeCl(3), but not heme, to the growth medium.
      The bhuQ gene is cotranscribed with the gene encoding the iron-responsive
      regulator RirA, and both of these genes are repressed by the other major iron
      responsive regulator in the alphaproteobacteria, Irr. The results of these
      studies suggest that B. abortus 2308 has at least one other heme oxygenase that
      works in concert with BhuQ to allow this strain to efficiently use heme as an
      iron source. The genetic organization of the rirA-bhuQ operon also provides the
      basis for the proposition that BhuQ may perform a previously unrecognized
      function by allowing the transcriptional regulator RirA to recognize heme as an
      iron source.

PMID- 22636784
TI  - Expanded roles for multicargo and class 1B effector chaperones in type III
      secretion.
AB  - Bacterial type III secretion systems (T3SS) are complex protein assemblies that
      mediate the secretion of protein substrates outside the cell. Type III secretion
      chaperones (T3SC) are always found associated with T3SS, and they serve in
      multiple roles to ensure that protein substrates are efficiently targeted for
      secretion. Bacterial pathogens with T3SS express T3SC proteins that bind
      effectors, a process important for effector protein delivery into eukaryotic
      cells during infection. In this minireview, we focus on multicargo and class 1B
      T3SC that associate with effectors within significant pathogens of animals and
      plants. As a primary role, multicargo and class 1B T3SC form homodimers and
      specifically bind different effectors within the cytoplasm, maintaining the
      effectors in a secretion-competent state. This role makes T3SC initial and
      central contributors to effector-mediated pathogenesis. Recent findings have
      greatly expanded our understanding of cellular events linked to multicargo T3SC
      function. New binding interactions with T3SS components have been reported in
      different systems, thereby implicating multicargo T3SC in critical roles beyond
      effector binding. Three notable interactions with the YscN, YscV, and YscQ family
      members are well represented in the literature. Similar T3SC interactions are
      reported in the putative related flagellar T3SS, suggesting that secretion
      mechanisms may be more similar than previously thought. The evidence implicates
      multicargo and class 1B T3SC in effector binding and stabilization, in addition
      to T3SS recruitment and docking events.

PMID- 22636785
TI  - OmpA is the principal nonspecific slow porin of Acinetobacter baumannii.
AB  - Acinetobacter species show high levels of intrinsic resistance to many
      antibiotics. The major protein species in the outer membrane of Acinetobacter
      baumannii does not belong to the high-permeability trimeric porin family, which
      includes Escherichia coli OmpF/OmpC, and instead is a close homolog of E. coli
      OmpA and Pseudomonas aeruginosa OprF. We characterized the pore-forming function
      of this OmpA homolog, OmpA(Ab), by a reconstitution assay. OmpA(Ab) produced very
      low pore-forming activity, about 70-fold lower than that of OmpF and an activity
      similar to that of E. coli OmpA and P. aeruginosa OprF. The pore size of the
      OmpA(Ab) channel was similar to that of OprF, i.e., about 2 nm in diameter. The
      low permeability of OmpA(Ab) is not due to the inactivation of this protein
      during purification, because the permeability of the whole A. baumannii outer
      membrane was also very low. Furthermore, the outer membrane permeability to
      cephalothin and cephaloridine, measured in intact cells, was about 100-fold lower
      than that of E. coli K-12. The permeability of cephalothin and cephaloridine in
      A. baumannii was decreased 2- to 3-fold when the ompA(Ab) gene was deleted. These
      results show that OmpA(Ab) is the major nonspecific channel in A. baumannii. The
      low permeability of this porin, together with the presence of constitutive beta
      lactamases and multidrug efflux pumps, such as AdeABC and AdeIJK, appears to be
      essential for the high levels of intrinsic resistance to a number of antibiotics.

PMID- 22636786
TI  - The drug industry is a barrier to diabetes care in poor countries.

PMID- 22636787
TI  - Full access to trial data holds many benefits and a few pitfalls, conference
      hears.

PMID- 22636788
TI  - Doctors opposed to NHS reforms set up a new political party.

PMID- 22636789
TI  - Health department is to shut down patient records site that was too hard to use.

PMID- 22636790
TI  - Catholics sue Obama over provision of contraception in health insurance policies.

PMID- 22636791
TI  - England and Wales finally get first chief coroner.

PMID- 22636799
TI  - New wrinkle between cancer and blood coagulation: metastasis and cleavage of von
      Willebrand factor by ADAM28.

PMID- 22636800
TI  - Effect of ADAM28 on carcinoma cell metastasis by cleavage of von Willebrand
      factor.
AB  - BACKGROUND: A disintegrin and metalloproteinase 28 (ADAM28) is implicated in
      tumor growth and metastasis in human breast and non-small cell lung carcinomas.
      We explored the mechanism of ADAM28-mediated metastasis by searching for new
      substrates of ADAM28. METHODS: We used a yeast two-hybrid system to screen the
      human lung cDNA library for ADAM28-binding proteins and identified von Willebrand
      factor (VWF) as a potential candidate. Binding was confirmed using yeast two
      hybrid and protein binding assays, and ADAM28-mediated cleavage of VWF was
      analyzed by immunoblotting. Exogenous VWF-induced apoptosis in vitro was examined
      in human lung carcinoma (PC-9 and Calu-3), breast carcinoma (MDA-MB231 and MCF
      7), renal cell carcinoma (Caki-2 and 769P), and hepatocellular carcinoma (HepG2)
      cells, and expression of ADAM28 was assessed by reverse transcription-polymerase
      chain reaction and immunoblotting. Effect on lung metastasis of PC-9 and MDA
      MB231 cells was assessed by knockdown of ADAM28 expression using short hairpin
      RNAs (ADAM28-shRNA) and small interfering RNAs (ADAM28-siRNA), and inhibition of
      activity using neutralizing anti-ADAM28 antibody, in a mouse xenograft model by
      in vivo imaging (n = 9 mice per group). All statistical tests were two-sided.
      RESULTS: ADAM28 could bind to and cleave native VWF. Cells with very low ADAM28
      expression (MCF-7, 769P, and HepG2) were susceptible to VWF-induced apoptosis,
      whereas cells with high expression (PC-9, Calu-3, MDA-MB231, and Caki-2) were
      resistant. Knockdown of ADAM28 expression in PC-9 and MDA-MB231 cells by shRNA
      showed increased carcinoma cell apoptosis mainly in lung blood vessels and
      statistically significantly decreased lung metastasis at week 3 after injection
      (PC-9-control [n = 9 mice] vs PC-9-ADAM28-shRNA [n = 9 mice]: mean count = 198 *
      10(6) vs 37 * 10(6) photons/s, difference = 161 * 10(6) photons/s, 95% confidence
      interval = 134 * 10(6) to 188 * 10(6) photons/s, P < .001). Similar inhibition of
      lung metastasis was observed with ADAM28-siRNA and anti-ADAM28 antibody.
      CONCLUSION: ADAM28 cleaves and inactivates proapoptotic VWF in carcinoma cells
      and enhances lung metastasis probably by promoting carcinoma cell survival within
      the blood vessels.

PMID- 22636821
TI  - Understanding the long-term benefits and dangers of intensive therapy of
      diabetes.

PMID- 22636820
TI  - Role of intensive glucose control in development of renal end points in type 2
      diabetes mellitus: systematic review and meta-analysis intensive glucose control
      in type 2 diabetes.
AB  - BACKGROUND: Aggressive glycemic control has been hypothesized to prevent renal
      disease in patients with type 2 diabetes mellitus. A systematic review was
      conducted to summarize the benefits of intensive vs conventional glucose control
      on kidney-related outcomes for adults with type 2 diabetes. METHODS: Three
      databases were systematically searched (January 1, 1950, to December 31, 2010)
      with no language restrictions to identify randomized trials that compared
      surrogate renal end points (microalbuminuria and macroalbuminuria) and clinical
      renal end points (doubling of the serum creatinine level, end-stage renal disease
      [ESRD], and death from renal disease) in patients with type 2 diabetes receiving
      intensive glucose control vs those receiving conventional glucose control.
      RESULTS: We evaluated 7 trials involving 28 065 adults who were monitored for 2
      to 15 years. Compared with conventional control, intensive glucose control
      reduced the risk for microalbuminuria (risk ratio, 0.86 [95% CI, 0.76-0.96]) and
      macroalbuminuria (0.74 [0.65-0.85]), but not doubling of the serum creatinine
      level (1.06 [0.92-1.22]), ESRD (0.69 [0.46-1.05]), or death from renal disease
      (0.99 [0.55-1.79]). Meta-regression revealed that larger differences in
      hemoglobin A1c between intensive and conventional therapy at the study level were
      associated with greater benefit for both microalbuminuria and macroalbuminuria.
      The pooled cumulative incidence of doubling of the serum creatinine level, ESRD,
      and death from renal disease was low (<4%, <1.5%, and <0.5%, respectively)
      compared with the surrogate renal end points of microalbuminuria (23%) and
      macroalbuminuria (5%). CONCLUSIONS: Intensive glucose control reduces the risk
      for microalbuminuria and macroalbuminuria, but evidence is lacking that intensive
      glycemic control reduces the risk for significant clinical renal outcomes, such
      as doubling of the serum creatinine level, ESRD, or death from renal disease
      during the years of follow-up of the trials.

PMID- 22636822
TI  - Prioritizing treatments in type 2 diabetes mellitus.

PMID- 22636824
TI  - Multiple behavior changes in diet and activity: a randomized controlled trial
      using mobile technology.
AB  - BACKGROUND: Many patients exhibit multiple chronic disease risk behaviors.
      Research provides little information about advice that can maximize simultaneous
      health behavior changes. METHODS: To test which combination of diet and activity
      advice maximizes healthy change, we randomized 204 adults with elevated saturated
      fat and low fruit and vegetable intake, high sedentary leisure time, and low
      physical activity to 1 of 4 treatments: increase fruit/vegetable intake and
      physical activity, decrease fat and sedentary leisure, decrease fat and increase
      physical activity, and increase fruit/vegetable intake and decrease sedentary
      leisure. Treatments provided 3 weeks of remote coaching supported by mobile
      decision support technology and financial incentives. During treatment,
      incentives were contingent on using the mobile device to self-monitor and attain
      behavioral targets; during follow-up, incentives were contingent only on
      recording. The outcome was standardized, composite improvement on the 4 diet and
      activity behaviors at the end of treatment and at 5-month follow-up. RESULTS: Of
      the 204 individuals randomized, 200 (98.0%) completed follow-up. The increase
      fruits/vegetables and decrease sedentary leisure treatments improved more than
      the other 3 treatments (P < .001). Specifically, daily fruit/vegetable intake
      increased from 1.2 servings to 5.5 servings, sedentary leisure decreased from
      219.2 minutes to 89.3 minutes, and saturated fat decreased from 12.0% to 9.5% of
      calories consumed. Differences between treatment groups were maintained through
      follow-up. Traditional dieting (decrease fat and increase physical activity)
      improved less than the other 3 treatments (P < .001). CONCLUSIONS: Remote
      coaching supported by mobile technology and financial incentives holds promise to
      improve diet and activity. Targeting fruits/vegetables and sedentary leisure
      together maximizes overall adoption and maintenance of multiple healthy behavior
      changes.

PMID- 22636825
TI  - Leveraging technology for multiple risk factor interventions.

PMID- 22636826
TI  - Effect of physician payment disclosure laws on prescribing.

PMID- 22636827
TI  - Characteristics of "complex" patients with type 2 diabetes mellitus according to
      their primary care physicians.

PMID- 22636828
TI  - Dabigatran and myocardial infarction: meta-illusion?

PMID- 22636830
TI  - A role for opioids in chronic pain management.

PMID- 22636832
TI  - Fecal transplant for Clostridium difficile.

PMID- 22637153
TI  - Prostaglandins but not leukotrienes alter extracellular matrix protein deposition
      and cytokine release in primary human airway smooth muscle cells and fibroblasts.
AB  - Eicosanoids are lipid-signaling mediators released by many cells in response to
      various stimuli. Increasing evidence suggests that eicosanoids such as
      leukotrienes and prostaglandins (PGs) may directly mediate remodeling. In this
      study, we assessed whether these substances could alter extracellular matrix
      (ECM) proteins and the inflammatory profiles of primary human airway smooth
      muscle cells (ASM) and fibroblasts. PGE(2) decreased both fibronectin and
      tenascin C in fibroblasts but only fibronectin in ASM. PGD(2) decreased both
      fibronectin and tenascin C in both ASM and fibroblasts, whereas PGF(2alpha) had
      no effect on ECM deposition. The selective PGI(2) analog, MRE-269, decreased
      fibronectin but not tenascin C in both cell types. All the PGs increased IL-6 and
      IL-8 release in a dose-dependent manner in ASM and fibroblasts. Changes in ECM
      deposition and cytokine release induced by prostaglandins in both ASM and
      fibroblasts were independent of an effect on cell number. Neither the acute nor
      repeated stimulation with leukotrienes had an effect on the deposition of ECM
      proteins or cytokine release from ASM or fibroblasts. We concluded that,
      collectively, these results provide evidence that PGs may contribute to ECM
      remodeling to a greater extent than leukotrienes in airway cells.

PMID- 22637154
TI  - Interactions among pulmonary surfactant, vernix caseosa, and intestinal
      enterocytes: intra-amniotic administration of fluorescently liposomes to pregnant
      rabbits.
AB  - Although vernix caseosa is known to be a natural biofilm at birth, human
      pulmonary surfactant commences to remove the vernix from fetal skin into the
      amniotic fluid at gestational week 34, i.e., well before delivery. To explain
      this paradox, we first produced two types of fluorescently labeled liposomes
      displaying morphology similar to that of pulmonary surfactant and vernix caseosa
      complexes. We then continuously administered these liposomes into the amniotic
      fluid space of pregnant rabbits. In addition, we produced pulmonary surfactant
      and vernix caseosa complexes and administered them into the amniotic fluid space
      of pregnant rabbits. The intra-amniotic infused fluorescently labeled liposomes
      were absorbed into the fetal intestinal epithelium. However, the liposomes were
      not transported to the livers of fetal rabbits. We also revealed that continuous
      administration of micelles derived from pulmonary surfactants and vernix caseosa
      protected the small intestine of the rabbit fetus from damage due to surgical
      intervention. Our results indicate that pulmonary surfactant and vernix caseosa
      complexes in swallowed amniotic fluid might locally influence fetal intestinal
      enterocytes. Although the present studies are primarily observational and further
      studies are needed, our findings elucidate the physiological interactions among
      pulmonary, dermal-epidermal, and gastrointestinal developmental processes.

PMID- 22637155
TI  - CFTR is required for maximal transepithelial liquid transport in pig alveolar
      epithelia.
AB  - A balance between alveolar liquid absorption and secretion is critical for
      maintaining optimal alveolar subphase liquid height and facilitating gas exchange
      in the alveolar space. However, the role of cystic fibrosis transmembrane
      regulator protein (CFTR) in this homeostatic process has remained elusive. Using
      a newly developed porcine model of cystic fibrosis, in which CFTR is absent, we
      investigated ion transport properties and alveolar liquid transport in isolated
      type II alveolar epithelial cells (T2AECs) cultured at the air-liquid interface.
      CFTR was distributed exclusively to the apical surface of cultured T2AECs.
      Alveolar epithelia from CFTR(-/-) pigs failed to increase liquid absorption in
      response to agents that increase cAMP, whereas cAMP-stimulated liquid absorption
      in CFTR(+/-) epithelia was similar to that in CFTR(+/+) epithelia. Expression of
      recombinant CFTR restored stimulated liquid absorption in CFTR(-/-) T2AECs but
      had no effect on CFTR(+/+) epithelia. In ex vivo studies of nonperfused lungs,
      stimulated liquid absorption was defective in CFTR(-/-) alveolar epithelia but
      similar between CFTR(+/+) and CFTR(+/-) epithelia. When epithelia were studied at
      the air-liquid interface, elevating cAMP levels increased subphase liquid height
      in CFTR(+/+) but not in CFTR(-/-) T2AECs. Our findings demonstrate that CFTR is
      required for maximal liquid absorption under cAMP stimulation, but it is not the
      rate-limiting factor. Furthermore, our data define a role for CFTR in liquid
      secretion by T2AECs. These insights may help to develop new treatment strategies
      for pulmonary edema and respiratory distress syndrome, diseases in which lung
      liquid transport is disrupted.

PMID- 22637202
TI  - Motion versus fixed distraction of the joint in the treatment of ankle
      osteoarthritis: a prospective randomized controlled trial.
AB  - BACKGROUND: Initial reports have shown the efficacy of fixed distraction for the
      treatment of ankle osteoarthritis. We hypothesized that allowing ankle motion
      during distraction would result in significant improvements in outcomes compared
      with distraction without ankle motion. METHODS: We conducted a prospective
      randomized controlled trial comparing the outcomes for patients with advanced
      ankle osteoarthritis who were managed with anterior osteophyte removal and either
      (1) fixed ankle distraction or (2) ankle distraction permitting joint motion.
      Thirty-six patients were randomized to treatment with either fixed distraction or
      distraction with motion. The patients were followed for twenty-four months after
      frame removal. The Ankle Osteoarthritis Scale (AOS) was the main outcome
      variable. RESULTS: Two years after frame removal, subjects in both groups showed
      significant improvement compared with the status before treatment (p < 0.02 for
      both groups). The motion-distraction group had significantly better AOS scores
      than the fixed-distraction group at twenty-six, fifty-two, and 104 weeks after
      frame removal (p < 0.01 at each time point). At 104 weeks, the motion-distraction
      group had an overall mean improvement of 56.6% in the AOS score, whereas the
      fixed-distraction group had a mean improvement of 22.9% (p < 0.01). CONCLUSION:
      Distraction improved the patient-reported outcomes of treatment of ankle
      osteoarthritis. Adding ankle motion to distraction showed an early and sustained
      beneficial effect on outcome.

PMID- 22637203
TI  - Activity levels are higher after osteochondral autograft transfer mosaicplasty
      than after microfracture for articular cartilage defects of the knee: a
      retrospective comparative study.
AB  - BACKGROUND: There is limited information regarding direct comparisons of the
      outcome of osteochondral autograft transfer (OAT) mosaicplasty and microfracture
      for the treatment of isolated articular cartilage defects of the knee. The
      purpose of this retrospective comparative study was to compare the general health
      outcomes, knee function, and Marx Activity Rating Scale scores for patients
      treated with OAT or microfracture for symptomatic chondral defects of the femoral
      condyles or trochlea. We hypothesized that the patients in the two treatment
      groups would have similar clinical outcomes at intermediate-term follow-up.
      METHODS: Ninety-six patients with full-thickness cartilage defects of the femoral
      condyles or trochlea were treated with either OAT mosaicplasty (n = 48) or
      microfracture (n = 48). The average age of the patients (thirty-two male and
      sixteen female in each group) at the time of surgery was 29.7 years in the OAT
      group and 32.5 years in the microfracture group. Patients were prospectively
      evaluated at baseline and at one, two, three, and five years postoperatively with
      use of validated clinical outcome measures including the Short Form-36 (SF-36)
      physical component, International Knee Documentation Committee (IKDC), Knee
      Outcome Survey activities of daily living, and Marx Activity Rating Scale
      instruments. Comparisons between outcomes before and after treatment or between
      outcomes after microfracture and mosaicplasty were made with use of two-tailed
      tests. RESULTS: At the time of the latest follow-up, both groups demonstrated
      significant increases in SF-36 physical component, Knee Outcome Survey activities
      of daily living, and IKDC scores compared with baseline. These scores did not
      differ significantly between the two groups at any of the follow-up time points.
      However, the OAT group demonstrated a significantly greater improvement in the
      Marx Activity Rating Scale scores from baseline to the two-year (p = 0.001),
      three-year (p = 0.03), and five-year (p = 0.02) time points compared with the
      microfracture group. CONCLUSIONS: In the present retrospective comparative study,
      the hypothesis that patients treated with microfracture or OAT mosaicplasty for
      symptomatic articular cartilage defects of the femoral condyles or trochlea would
      have similar clinical outcomes at intermediate-term follow-up was affirmed for
      general health outcome and for knee function. However, patients treated with OAT
      mosaicplasty maintained a superior level of athletic activity compared with those
      treated with microfracture.

PMID- 22637204
TI  - NeoCart, an autologous cartilage tissue implant, compared with microfracture for
      treatment of distal femoral cartilage lesions: an FDA phase-II prospective,
      randomized clinical trial after two years.
AB  - BACKGROUND: Despite introduction of autologous chondrocyte therapy for repair of
      hyaline articular cartilage injury in 1994, microfracture remains a primary
      standard of care. NeoCart, an autologous cartilage tissue implant, was compared
      with microfracture in a multisite prospective, randomized trial of a tissue
      engineered bioimplant for treating articular cartilage injuries in the knee.
      METHODS: Thirty patients were randomized at a ratio of two to one (two were
      treated with an autologous cartilage tissue implant [NeoCart] for each patient
      treated with microfracture) at the time of arthroscopic confirmation of an
      International Cartilage Repair Society (ICRS) grade-III lesion(s). Microfracture
      or cartilage biopsy was performed. NeoCart, produced by seeding a type-I collagen
      matrix scaffold with autogenous chondrocytes and bioreactor treatment, was
      implanted six weeks following arthroscopic cartilage biopsy. Standard evaluations
      were performed with validated clinical outcomes measures. RESULTS: Three, six,
      twelve, and twenty-four-month data are reported. The mean duration of follow-up
      (and standard deviation) was 26 +/- 2 months. There were twenty-one patients in
      the NeoCart group and nine in the microfracture group. The mean age (40 +/- 9
      years), body mass index (BMI) (28 +/- 4 kg/m2), duration between the first
      symptoms and treatment (3 +/- 5 years), and lesion size (287 +/- 138 mm2 in the
      NeoCart group and 252 +/- 135 mm2 in the microfracture group) were similar
      between the groups. Adverse event rates per procedure did not differ between the
      treatment arms. The scores on the Short Form-36 (SF-36), Knee Injury and
      Osteoarthritis Outcome Score (KOOS) activities of daily living (ADL) scale, and
      International Knee Documentation Committee (IKDC) form improved from baseline (p
      < 0.05) to two years postoperatively in both treatment groups. In the NeoCart
      group, improvement, compared with baseline, was significant (p < 0.05) for all
      measures at six, twelve, and twenty-four months. Improvement in the NeoCart group
      was significantly greater (p < 0.05) than that in the microfracture group for the
      KOOS pain score at six, twelve, and twenty-four months; the KOOS symptom score at
      six months; the IKDC, KOOS sports, and visual analog scale (VAS) pain scores at
      twelve and twenty-four months; and the KOOS quality of life (QOL) score at twenty
      four months. Analysis of covariance (ANCOVA) at one year indicated that the
      change in the KOOS pain (p = 0.016) and IKDC (p = 0.028) scores from pretreatment
      levels favored the NeoCart group. Significantly more NeoCart-treated patients (p
      = 0.0125) had responded to therapy (were therapeutic responders) at six months
      (43% versus 25% in the microfracture group) and twelve months (76% versus 22% in
      the microfracture group). This trend continued, as the proportion of NeoCart
      treated patients (fifteen of nineteen) who were therapeutic responders at twenty
      four months was greater than the proportion of microfracture-treated participants
      (four of nine) who were therapeutic responders at that time. CONCLUSIONS: This
      randomized study suggests that the safety of autologous cartilage tissue
      implantation, with use of the NeoCart technique, is similar to that of
      microfracture surgery and is associated with greater clinical efficacy at two
      years after treatment.

PMID- 22637205
TI  - Cylindrical costal osteochondral autograft for reconstruction of large defects of
      the capitellum due to osteochondritis dissecans.
AB  - BACKGROUND: There is a need to clarify the usefulness of and problems associated
      with cylindrical costal osteochondral autograft for reconstruction of large
      defects of the capitellum due to osteochondritis dissecans. METHODS: Twenty-six
      patients with advanced osteochondritis dissecans of the humeral capitellum were
      treated with use of cylindrical costal osteochondral autograft. All were males
      with elbow pain and full-thickness articular cartilage lesions of >=15 mm in
      diameter. Clinical, radiographic, and magnetic resonance imaging outcomes were
      evaluated at a mean follow-up of thirty-six months (range, twenty-four to fifty
      one months). RESULTS: All patients had rapid functional improvement after
      treatment with costal osteochondral autograft and returned to their former
      activities, including sports. Five patients needed additional minor surgical
      procedures, including screw removal, loose body removal, and shaving of protruded
      articular cartilage. Mean elbow function, assessed with use of the clinical
      rating system of Timmerman and Andrews, was 111 points preoperatively and
      improved to 180 points at the time of follow-up and to 190 points after the five
      patients underwent the additional operations. Mean elbow motion was 126 degrees 
      of flexion with 16 degrees  of extension loss preoperatively and improved to 133
      degrees  of flexion with 3 degrees  of extension loss at the time of follow-up.
      Osseous union of the graft on radiographs was obtained within three months in all
      patients. Revascularization of the graft depicted on T1-weighted magnetic
      resonance imaging and congruity of the reconstructed articular surface depicted
      on T2-weighted or short tau inversion recovery imaging were assessed at twelve
      and twenty-four months postoperatively. Functional recovery was good, and all
      patients were satisfied with the final outcomes. CONCLUSIONS: Cylindrical costal
      osteochondral autograft was useful for the treatment of advanced osteochondritis
      dissecans of the humeral capitellum. Functional recovery was rapid after surgery.
      Additional operations were performed for five of the twenty-six patients, whereas
      the remaining patients showed essentially full recovery within a year. All
      patients were satisfied with the results at the time of short-term follow-up.

PMID- 22637206
TI  - The effect of the remplissage procedure on shoulder stability and range of
      motion: an in vitro biomechanical assessment.
AB  - BACKGROUND: The remplissage procedure may be performed as an adjunct to Bankart
      repair to treat recurrent glenohumeral dislocation associated with an engaging
      Hill-Sachs humeral head defect. The purpose of this in vitro biomechanical study
      was to examine the effects of the remplissage procedure on glenohumeral joint
      motion and stability. METHODS: Cadaveric shoulders (n = 8) were mounted on a
      biomechanical testing apparatus that applies simulated loads to the rotator cuff
      and the anterior, middle, and posterior heads of the deltoid muscle. Testing was
      performed with the shoulder intact, after creation of the Bankart lesion, and
      after repair of the Bankart lesion. In addition, testing was performed after
      Bankart repair with and without remplissage in shoulders with 15% and 30% Hill
      Sachs defects. Shoulder motion and glenohumeral translation were recorded with an
      optical tracking system. Outcomes measured included stability (joint stiffness
      and defect engagement) and internal-external glenohumeral rotational motion in
      adduction and in 90 degrees  of composite shoulder abduction. RESULTS: In
      specimens with a 15% Hill-Sachs defect, Bankart repair combined with remplissage
      resulted in a significant reduction in internal-external range of motion in
      adduction (15.1 degrees  +/- 11.1 degrees , p = 0.039), but not in abduction (7.7
      degrees  +/- 9.9, p = 0.38), compared with the intact condition. In specimens
      with a 30% Hill-Sachs defect, repair that included remplissage also significantly
      reduced internal-external range of motion in adduction (14.5 degrees  +/- 11.3
      degrees , p = 0.049) but not in abduction (6.2 degrees  +/- 9.3 degrees , p =
      0.60). In specimens with a 15% Hill-Sachs defect, addition of remplissage
      significantly increased joint stiffness compared with isolated Bankart repair (p
      = 0.038), with the stiffness trending toward surpassing the level in the intact
      condition (p = 0.060). In specimens with a 30% Hill-Sachs defect, addition of
      remplissage restored joint stiffness to approximately normal (p = 0.41 compared
      with the intact condition). All of the specimens with a 30% Hill-Sachs defect
      engaged and dislocated after Bankart repair alone. The addition of remplissage
      was effective in preventing engagement and dislocation in all specimens. None of
      the specimens with a 15% Hill-Sachs defect engaged or dislocated after Bankart
      repair. CONCLUSIONS: In this experimental model, addition of remplissage provided
      little additional benefit to a Bankart repair in specimens with a 15% Hill-Sachs
      defect, and it also reduced specific shoulder motions. However, Bankart repair
      alone was ineffective in preventing engagement and recurrent dislocation in
      specimens with a 30% Hill-Sachs defect. The addition of remplissage to the
      Bankart repair in these specimens prevented engagement and enhanced stability,
      although at the expense of some reduction in shoulder motion.

PMID- 22637207
TI  - Pain, physical and social functioning, and quality of life in individuals with
      multiple hereditary exostoses in The Netherlands: a national cohort study.
AB  - BACKGROUND: This study aimed to assess pain and quality of life in a large cohort
      of patients with multiple hereditary exostoses. METHODS: All 322 known patients
      with multiple hereditary exostoses in The Netherlands were asked to participate.
      An age-specific questionnaire was sent to children (less than eighteen years old)
      and adults. The questionnaire focused on pain, daily activities, and school
      and/or professional situation. Adults also filled out the RAND-36 questionnaire.
      Results were statistically analyzed with use of the SPSS 15.0 software and with
      the chi-square test and multiple logistic regression. A p value of <0.05 was
      regarded as significant. RESULTS: Two hundred and eighty-three patients (88%),
      including 184 adults (65%) and ninety-nine children (35%), completed the
      questionnaire. Multiple hereditary exostoses resulted in various physical and
      social consequences. The majority of adults (119) were employed; however, thirty
      three (28%) had changed jobs because of the symptoms of multiple hereditary
      exostoses and twenty-five (21%) required adjustments in their working
      environment. Of the sixty-five adults who were not employed, thirteen were
      medically unfit to work. Of eighty-five children attending school, forty-five
      (53%) experienced problems at school. The symptoms of multiple hereditary
      exostoses caused twenty-seven children (27%) and eighty-five adults (46%) to stop
      participating in sporting activities. Pain was the greatest problem, with sixty
      two children (63%) and 152 adults (83%) who reported recent pain. On multivariate
      analysis, pain in adults was correlated most significantly with age and problems
      at work, and pain in children was correlated with the perception of the disease
      and problems at school. Adult patients with multiple hereditary exostoses had a
      lower quality of life than the Dutch reference groups, with lower scores on six
      of eight RAND-36 subscales. CONCLUSIONS: Our study confirms that multiple
      hereditary exostoses is a chronic disease causing a profound impact on quality of
      life. The results suggest that pain is not the only problem associated with
      multiple hereditary exostoses, as it has an extensive influence on daily
      activities, as well as on social and psychological well-being, causing
      significant disability.

PMID- 22637208
TI  - Influence of limb alignment on mediolateral loading in total knee replacement: in
      vivo measurements in five patients.
AB  - BACKGROUND: Malalignment after total knee replacement could cause overloading of
      the implant bearing as well as of the bone itself, leading to osteolysis and
      early loosening. To quantify the stresses the implant has to withstand and to
      define a safe zone of limb alignment, the total contact forces as well as their
      mediolateral distribution have to be determined. Analytical gait data and
      mathematical models have been used for this purpose. We performed this study to
      determine in vivo loads of five patients after implantation of an instrumented
      tibial baseplate. METHODS: Five patients with osteoarthritis of the knee received
      total knee replacement. The tibial component was instrumented with strain gauges
      for the measurement of three forces and three moments. The signals from the
      gauges were transferred telemetrically to an external receiver. At twelve months
      after surgery, postoperative measurements were obtained with the patients walking
      at a self-selected comfortable speed across a level walkway. Peak axial and
      medial forces of fifteen to twenty gait cycles were averaged and reported as a
      percent of individual body weight. RESULTS: During the stance phase of the gait
      cycle, two maxima of the axial force occurred. Typical values were 215% of body
      weight at the first peak and 266% of body weight at the second peak. The medial
      load share was typically 73% at the first axial force peak and 65% at the second
      axial force peak. Analysis of inter-individual variations revealed a linear
      correlation with limb alignment. A deviation of 1 degrees  varus from neutral
      alignment increased the medial load share by 5%. CONCLUSIONS: Consistent with the
      results of previous studies, we found that the force transferred by the medial
      compartment was usually greater than that transferred by the lateral compartment.
      Concerning the design of total knee replacements, an asymmetric tibial component
      with a larger medial contact area could possibly reduce peak contact stress on
      the bone and improve fixation of the implant. Mediolateral load distribution was
      quantified and correlated with limb alignment, thereby permitting the effects of
      malalignment after total knee replacement to be estimated.

PMID- 22637209
TI  - Injury patterns causing isolated foot compartment syndrome.
AB  - BACKGROUND: The true incidence and primary predictors of foot compartment
      syndrome remain controversial. Our aim was to better define the overall incidence
      of foot compartment syndrome in relation to the frequency and location of various
      foot injuries. We hypothesized that (1) the incidence would increase in
      proportion to the number of anatomic locations of injury, (2) the incidence would
      be higher in association with hindfoot and crush injuries compared with any other
      injury categories, and (3) not only would the incidence associated with calcaneal
      fractures be lower than the often quoted 10% but foot compartment syndrome would
      also be fairly uncommon after such fractures. METHODS: The National Trauma Data
      Bank was used to identify patients who had undergone a fasciotomy for the
      treatment of isolated foot compartment syndrome. Strict inclusion and exclusion
      criteria were used to identify only patients with foot injuries who had undergone
      fasciotomy for foot compartment syndrome. RESULTS: Three hundred and sixty-four
      patients with an isolated foot compartment syndrome were identified. The highest
      incidence of foot compartment syndrome was seen in association with a crush
      mechanism combined with a forefoot injury (18%, nineteen of 106), followed by an
      isolated crush injury (14%, twenty-three of 162). Only 1% (thirty-two) of 2481
      patients with an isolated calcaneal fracture underwent fasciotomy. An increase in
      the number of anatomic locations of injury did not appear to correspond to an
      increased incidence of foot compartment syndrome. CONCLUSION: Our results
      demonstrate that injuries involving a crush mechanism, either in isolation or in
      combination with a forefoot injury, should raise suspicion about the possibility
      that a foot compartment syndrome will develop.

PMID- 22637211
TI  - Impact of obesity on orthopaedics.
AB  - The prevalence of obesity among children and adults is increasing worldwide.
      There are substantial health risks and financial costs associated with the
      obesity epidemic that impact the practice of orthopaedic surgery. Patients with
      increased body mass index are more prone to sustaining distal extremity injuries
      than are those with a normal body mass index. Obese individuals are more likely
      than nonobese individuals to seek treatment for osteoarthritis of the knee.

PMID- 22637210
TI  - The clinical utility and diagnostic performance of MRI for identification and
      classification of knee osteochondritis dissecans.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is a common clinical tool used to
      diagnose and monitor the progression and/or healing of osteochondritis dissecans
      of the knee. The purpose of this study was to systematically review the
      literature relative to the following questions: (1) Is MRI a valid, sensitive,
      specific, accurate, and reliable imaging modality to identify knee
      osteochondritis dissecans compared with arthroscopy? (2) Is MRI a sensitive tool
      that can be utilized to characterize lesion severity and stability of
      osteochondritis dissecans fragments in the knee? METHODS: A systematic search was
      performed in December 2010 with use of PubMed MEDLINE (from 1966), CINAHL (from
      1982), SPORTDiscus (from 1985), Scopus (from 1996), and EMBASE (from 1974)
      databases. RESULTS: Seven studies, four Level-II and three Level-III
      investigations, met the specified inclusion criteria. No randomized controlled
      studies were identified. Because of inconsistencies between imaging techniques
      and methodological shortcomings of many of the studies, a meta-analysis was not
      performed. CONCLUSIONS: The limited available evidence, methodological
      inconsistencies in imaging techniques, and lack of standardized grading criteria
      used in current studies prevent clear conclusions regarding the diagnostic and
      specific staging equivalency of MRI with arthroscopy. However, available evidence
      supports the use of MRI to detect the stability or instability of the lesion.
      Given the benefits of the use of MRI as a noninvasive tool to diagnose, predict
      lesion progression, and assess clinical outcomes of treatment, there is a
      pressing need for high-level, systematic, sound, and thorough studies related to
      the clinical utility of MRI for assessing osteochondritis dissecans of the knee.

PMID- 22637212
TI  - The hook plate technique for fixation of phalangeal avulsion fractures.
AB  - BACKGROUND: Avulsion fractures of the phalanges involve small osseous fragments
      that are usually attached to structures that are necessary for stability or
      movement of the joint. Satisfactory healing of the fracture to preserve joint
      function may require open reduction and internal fixation, which can be difficult
      because of the small size of the fragments. METHODS: We used a hook plate
      fashioned from a 1.3-mm Synthes titanium plate in thirteen patients with a
      phalangeal avulsion fracture. Four patients had an avulsion fracture of the volar
      plate with dorsal proximal interphalangeal joint dislocation, four had a dorsal
      avulsion fracture of the extensor central slip from the middle phalanx, three had
      a flexor digitorum profundus avulsion fracture from the distal phalanx, and two
      had an avulsion fracture of the phalangeal insertion of the collateral ligament.
      RESULTS: Union without complications was achieved in all cases. After an average
      duration of follow-up of seventeen months, all patients had a good to excellent
      result and the average total interphalangeal motion was 149 degrees .
      CONCLUSIONS: This indirect fixation technique produces stable fixation allowing
      early active finger motion.

PMID- 22637213
TI  - Minimally invasive approach for the treatment of non-isolated congenital vertical
      talus.
AB  - BACKGROUND: Traditional extensive soft-tissue release for the treatment of
      congenital vertical talus is associated with a myriad of complications. A
      minimally invasive approach has recently been introduced with good short-term
      results in patients with isolated vertical talus. The purpose of the present
      study was to evaluate the effectiveness of this approach for the treatment of
      rigid vertical talus associated with neuromuscular and/or genetic syndromes.
      METHODS: Fifteen consecutive patients (twenty-five feet) with non-isolated
      congenital vertical talus were retrospectively reviewed at a minimum of two years
      following treatment with serial casting followed by limited surgery. The surgery
      consisted of percutaneous Achilles tenotomy in all feet and either pin fixation
      of the talonavicular joint through a small medial incision to ensure joint
      reduction and accurate pin placement (five feet) or selective capsulotomies of
      the talonavicular joint and the anterior aspect of the subtalar joint (twenty
      feet). Patients were evaluated clinically and radiographically at the time of
      presentation, immediately postoperatively, and at the time of the latest follow
      up. Radiographic data at the time of the latest follow-up were compared with age
      matched normative values. RESULTS: Initial correction was obtained in all cases.
      The mean number of casts required was five. Mean ankle dorsiflexion was 22
      degrees  and mean plantar flexion was 25 degrees  at the time of the latest
      follow-up. Recurrence was noted in three patients (five feet), all of whom had
      had initial subluxation of the calcaneocuboid joint. All radiographic parameters
      measured at the time of the latest follow-up had improved significantly (p <
      0.0001) compared with the values before treatment, and the mean values of the
      measured angles did not differ significantly from age-matched normal values.
      CONCLUSIONS: Serial manipulation and casting followed by limited surgery,
      consisting of percutaneous tenotomy of the Achilles tendon and a small medial
      incision to either palpate the talonavicular joint or perform capsulotomies of
      the talonavicular joint and the anterior aspect of the subtalar joint to ensure
      accurate reduction and pin fixation, result in excellent short-term correction of
      the deformity while preserving subtalar and ankle motion in patients with rigid
      congenital vertical talus associated with neuromuscular and/or genetic syndromes.

PMID- 22637215
TI  - The Latarjet procedure for the treatment of recurrence of anterior instability of
      the shoulder after operative repair: a retrospective case series of forty-nine
      consecutive patients.
AB  - BACKGROUND: Recurrence of anterior shoulder instability after operative repair is
      an uncommon but disabling condition for which treatment options have been
      insufficiently studied. Coracoid transfer as described by Latarjet is a highly
      successful primary operation for recurrent anterior shoulder instability. The
      purpose of this study was to verify the hypothesis that this procedure is also
      effective for treating recurrent glenohumeral instability after previous
      operative repair. METHODS: Forty-nine consecutive patients with either one (n =
      32), two (n = 12), or at least three (n = 5) previous stabilizations other than a
      Latarjet procedure and recurrence of anterior glenohumeral instability associated
      with a lesion of the anterior aspect of the glenoid rim had revision with a
      coracoid transfer as described by Latarjet. Clinical outcomes at a mean of thirty
      eight months postoperatively included the subjective shoulder value, the Constant
      Murley score, and glenohumeral stability. Standardized anteroposterior and axial
      radiographs before and after the Latarjet revision were used to grade the degree
      of glenohumeral osteoarthritis. RESULTS: The results in all forty-nine patients
      were reviewed. No shoulder redislocated, subluxations recurred in two patients,
      and five patients reported slight, unspecified shoulder symptoms. No revision
      surgery was needed. Forty-three shoulders (88%) were subjectively graded as
      excellent or good; three, fair; and three, poor. Dissatisfaction was associated
      with persistent pain, and patients with preoperative pain had a twentyfold higher
      probability of having postoperative pain. The mean subjective shoulder value
      increased from 53% preoperatively to 79% at the time of follow-up (p < 0.001),
      and the Constant-Murley score remained high (80% preoperatively and 85% at the
      time of follow-up; p = 0.061). Optimal graft placement was obtained in thirty
      cases and was related to better clinical outcome and less progression of
      osteoarthritis than was suboptimal graft placement. CONCLUSIONS: Coracoid
      transfer as described by Latarjet can effectively restore anterior glenohumeral
      shoulder stability if previous operation(s) have failed to do so. If recurrence
      is associated with chronic pain, the pain is likely to persist and compromise the
      subjective outcome.

PMID- 22637214
TI  - Long-term outcomes of lumbar posterior apophyseal end-plate lesions in children
      and adolescents.
AB  - BACKGROUND: A lesion of the lumbar posterior apophyseal end plate in children and
      adolescents causes symptoms similar to those associated with a herniated disc.
      However, the end-plate lesion and the herniated disc differ in terms of
      pathology. The purpose of this study was to clarify the long-term clinical and
      radiographic outcomes in children and adolescents who were treated either
      surgically or conservatively for a lumbar posterior apophyseal end-plate lesion.
      METHODS: We identified twenty-four consecutive patients who had been treated in
      the sports clinic of our hospital. The mean age at the first medical examination
      was 14.5 years. The mean follow-up time was 13.8 years. The mean age at the time
      of final follow-up was 28.4 years. All twenty-four patients had symptomatic low
      back pain with sciatica. All but two were active in sports. Sixteen patients were
      treated conservatively, and eight patients underwent surgical intervention.
      Skeletal maturity was evaluated on the basis of the appearance of the secondary
      ossification center of L3. RESULTS: The apophyseal stage ("A" stage), which was
      assigned when the secondary ossification center of the vertebral body was visible
      on radiographs, was seen most frequently. Both the surgically treated group and
      the conservatively treated group demonstrated progressive disc degeneration at
      the involved level. The average Roland-Morris Disability Questionnaire (RDQ)
      score was 1.3 for the patients treated conservatively and 1.8 for those treated
      surgically, a nonsignificant difference. One patient developed spinal stenosis
      after twelve years of conservative treatment. One patient treated surgically
      demonstrated severe lumbar instability. There were no significant associations
      between the magnetic resonance imaging (MRI) findings and RDQ scores.
      Histological examination of surgical specimens showed irregular alignment of the
      anulus fibrosus, with degenerative matrix and chondrocytes without a nucleus.
      CONCLUSIONS: The long-term outcome for patients with a posterior end-plate lesion
      is favorable, regardless of whether it is treated surgically or nonsurgically.

PMID- 22637216
TI  - A novel nonsense mutation of the EXT1 gene in an Argentinian patient with
      multiple hereditary exostoses: a case report.

PMID- 22637217
TI  - Childbearing and pregnancy characteristics of female orthopaedic surgeons.
AB  - BACKGROUND: The number of women entering orthopaedic surgery is steadily
      increasing. Information regarding pregnancy and childbearing is important to
      understand as it increasingly affects residency programs, clinical practices, and
      the female surgeons and their offspring. METHODS: One thousand and twenty-one
      female surgeons completed an anonymous, voluntary, 199-item online survey
      distributed via individual female surgeon interest groups and word of mouth in
      nine specialties: general surgery, gynecology, neurosurgery, ophthalmology,
      orthopaedics, otolaryngology, plastic surgery, podiatry, and urology. Two hundred
      and twenty-three survey responses from orthopaedic surgeons were compared with
      those of the other surgical specialists as well as American Pregnancy Association
      national data to assess differences, if any, in pregnancy characteristics,
      demographics, and satisfaction. RESULTS: The overall reported complication rate
      for all pregnancies among orthopaedic surgeons was significantly higher than the
      rate in the general American population (31.2% [eighty-two of 263] compared with
      14.5%). There was an increased risk of preterm delivery among orthopaedic
      surgeons compared with a cohort of the general U.S. population matched according
      to age, race, health, and socioeconomic status (risk ratio, 2.5; 95% confidence
      interval [CI], 1.3 to 4.6). There was an increased risk of preterm labor and
      preterm delivery among women who reported working more than sixty hours per week
      (odds ratio, 4.95; 95% CI, 1.4 to 36.6). Female orthopaedic surgeons took shorter
      maternity leave during training than during clinical practice (median, four
      compared with seven weeks). The mean duration of breastfeeding was significantly
      shorter during training than during clinical practice (4.7 compared with 8.3
      months, p = 0.03). CONCLUSIONS: Female orthopaedic surgeons had an increased risk
      of pregnancy complications, particularly preterm delivery, compared with the
      general U.S. population. We found an increased risk of increased risk of preterm
      labor and delivery in surgeons working more than sixty hours per week during
      pregnancy.

PMID- 22637218
TI  - Why do medical students choose orthopaedics as a career?
AB  - BACKGROUND: The primary influence on medical students' career choice is their
      third-year clerkship. However, orthopaedics is not a required rotation in the
      curriculum of most medical schools. Our goals were to identify factors that
      motivate students to choose an orthopaedic career and to compare these with the
      factors that influence students to choose nonorthopaedic disciplines. METHODS:
      Fourth-year medical students and orthopaedic residents at the postgraduate year
      (PGY)-1 level at eight orthopaedic training programs in the United States were
      surveyed to determine the reasons that they chose orthopaedics instead of other
      medical or surgical fields. RESULTS: Of the 622 individuals who responded to our
      survey, 125 were entering orthopaedics and 497 were not. Although career choice
      in both groups was most heavily influenced by third and fourth-year clinical
      rotations and faculty contacts, orthopaedics-bound respondents were more likely
      than non-orthopaedics-bound respondents to be strongly influenced by experiences
      and people prior to medical school. Orthopaedics-bound respondents were less
      likely to report a faculty member as the most important person influencing career
      choice. Fifty-one percent (sixty-three) of 124 students who selected orthopaedics
      had already decided to pursue this field prior to their third-year rotation.
      Patient care was chosen by 71% (347) of 490 non-orthopaedics-bound respondents
      and 75% (ninety-four) of 125 orthopaedics-bound respondents as the most important
      factor for pursuing a particular field. Income was not selected as the deciding
      factor by respondents in either group. CONCLUSIONS: Although faculty contacts and
      third-year clinical rotations played an important role in student selection of
      specialty training, they were less influential for those choosing an orthopaedic
      career than for those choosing other disciplines. Many students choosing
      orthopaedics made this decision prior to medical school. We believe that
      increased exposure to positive clinical role models and experiences during
      medical school would enhance medical students' options for choosing orthopaedic
      surgery as a career. Anticipated income did not play a deciding role in career
      selection.

PMID- 22637219
TI  - Moving on with the distraction: commentary on an article by Charles L. Saltzman,
      MD, et al.: "Motion versus fixed distraction of the joint in the treatment of
      ankle osteoarthritis. A prospective randomized controlled trial".

PMID- 22637220
TI  - Fibrocartilage following microfracture is not as robust as native articular
      cartilage: commentary on an article by Aaron J. Krych, MD, et al.: "Activity
      levels are higher after osteochondral autograft transfer mosaicplasty than after
      microfracture for articular cartilage defects of the knee. A retrospective
      comparative study".

PMID- 22637221
TI  - Multiple hereditary exostoses: its burden on childhood and beyond: commentary on
      an article by A.L. Goud, MD, et al.: "Pain, physical and social functioning, and
      quality of life in individuals with multiple hereditary exostoses in The
      Netherlands. A national cohort study".

PMID- 22637287
TI  - Atrial fibrillation associated with epileptic seizures.
AB  - BACKGROUND: Epileptic seizures are often associated with changes in cardiac
      autonomic function. Yet atrial fibrillation (AFib) or atrial flutter (AFlu)
      following epileptic seizures has only rarely been reported in the past.
      OBJECTIVES: To describe and characterize patients who experienced lone AFib or
      AFlu as a consequence of epileptic seizures. DESIGN: Case reports. SETTING:
      University teaching hospital. PATIENTS: We describe 4 patients who developed
      transient AFib following epileptic seizures and 1 patient who developed transient
      AFlu following epileptic seizures. RESULTS: In all patients, AFib and AFlu
      followed a generalized tonic-clonic seizure. The arrhythmia usually lasted a few
      hours and converted spontaneously to a normal sinus rhythm. In 3 patients, AFib
      or AFlu developed during the first seizure they experienced, and none of the
      patients developed drug-resistant epilepsy. Moreover, none of the patients had a
      known cardiac disease, yet, in 2 patients, the cardiological workup demonstrated
      mild abnormalities on the cardiac stress test. CONCLUSIONS: Atrial fibrillation
      is the most common type of arrhythmia, with an estimated prevalence of 1%.
      Despite the fact that AFib can cause syncope, it is important to consider the
      possibility of AFib developing secondary to an epileptic seizure in cases of AFib
      and transient loss of consciousness.

PMID- 22637360
TI  - Overweight and lifestyle among 13-15 year olds: a cross-sectional study in
      northern Sweden.
AB  - AIM: To increase knowledge of self-rated health and lifestyle in relation to
      overweight/obesity among 13-15 year olds in northern Sweden. METHODS: All 6768 13
      15 year olds in nine out of 15 municipalities in Vasterbotten County were asked
      to complete a cross-sectional school-based on-line survey in 2007. Eighty-two per
      cent participated in the study. Responses were considered reliable for 74% of the
      participants (2517 boys/2470 girls). The survey addressed demography, self-rated
      health, self-reported weight, height, and lifestyle characteristics. Simple and
      multiple logistic regression analyses were used. RESULTS: Overweight/obesity (ISO
      body mass index >=25 kg/m(2)) was more prevalent among boys (20%) than girls
      (11%), but more girls (19%) than boys (9%) reported fair or bad health.
      Overweight/obese boys and girls were more often physically inactive. For the
      boys, overweight/obesity was also associated with skipping breakfast,
      insufficient tooth brushing, and using snuff. For the girls, overweight/obesity
      was also associated with living with one parent and more television watching.
      Boys reported healthier habits concerning sleep duration, physical activity,
      eating breakfast, and smoking compared to the girls. On the other hand, girls
      reported better dietary and tooth brushing habits. CONCLUSIONS: This study
      uncovered two alarming findings: a fifth of the boys were overweight/obese and a
      fifth of the girls reported fair or bad health. Girls living with a single parent
      and boys and girls with unhealthy lifestyles were more likely to be overweight.
      Our findings emphasise the need for developing and implementing effective health
      promotion strategies for school-aged children to prevent an overweight and
      obesity epidemic that could continue into adulthood.

PMID- 22637361
TI  - Urbanisation and the nutrition transition: a comparison of diet and weight status
      of South African and Kenyan women.
AB  - AIMS: To determine and compare the extent of the nutrition transition between
      Kenyan and South African women. METHODS: A nationally representative sample of
      women aged >=15 years (n=1008) was assessed in Kenya. Weight, height, and waist
      and hip circumferences were measured. A 24-hour dietary recall was conducted with
      each participant. This data was compared with data of the Demographic and Health
      Survey (DHS) of women in South Africa (n=4481). Dietary intake of South African
      women was based on secondary data analysis of dietary studies using the 24-hour
      recall method (n=1726). RESULTS: In South Africa, 27.4% women had a BMI >=30
      kg/m(2) compared with 14.2% of Kenyan women. In both countries there were large
      urban-rural differences in BMI, with the highest prevalence in women in urban
      areas. BMI increased with age, as did abdominal obesity which was equally
      prolific in both countries with more than 45% of women in the older groups having
      a waist/hip ratio >=0.85. The nutrient mean adequacy ratio (MAR) of the South
      African rural diet was lower than those of the Kenyans diet (55.9; 57.3%,
      respectively). Dietary diversity score (DDS) and food variety score (FVS) were
      significantly lower in South African rural women (3.3; 4.9) compared with Kenyans
      (4.5; 6.8). CONCLUSIONS: Urban-rural differences in diet and weight status
      indicates that the nutrition transition was similar in both countries despite
      large sociodemographic differences; however, rural Kenyan women had a better MAR,
      DDS, and FVS than South African women, most probably due to 60% having access to
      land.

PMID- 22637362
TI  - Lesbian women coping with challenges of minority stress: a qualitative study.
AB  - AIMS: Even though homosexuality is apparently widely accepted, minority stress
      prevails. Successful coping may reduce the negative impact of minority stress on
      health. We wanted to explore lesbian women's positive coping experiences related
      to sexual minority stress. METHODS: A convenience sample of self-defined lesbian
      women living in Norway was recruited mainly via internet. Qualitative data about
      coping strategies were obtained as written answers to a web-based, open-ended
      questionnaire. Data were analysed with systematic text condensation supported by
      theories of stress and coping, and salutogenesis. RESULTS: Openness about the
      lesbian orientation, and how disclosure was carried out, were means to counter
      anticipated prejudice. Maintaining dignity when prejudice appeared could be
      accomplished by actions to demand one's rights or claim respect, or by
      unexpressed thoughts boosting self-respect when unable to talk back. Prejudice
      within family relations lead to compromises to enable contact, but never
      compromising self-respect. Underlying successful coping strategies we identified
      a personal conviction that being lesbian is respectable and worthy - lesbian
      confidence. CONCLUSIONS: Promoting lesbian confidence, a healthcare provider can
      contribute to psychological wellbeing and enhance health among lesbian women.
      Open lesbian women in the community, who are responded to in a positive or every
      day-like manner, may nurture lesbian confidence and contribute to coping and
      health.

PMID- 22637363
TI  - Experiences from a randomised, controlled trial on cycling to school: does
      cycling increase cardiorespiratory fitness?
AB  - AIMS: The objective of the present study was to investigate the effect of a 12
      week randomised controlled cycling-to-school trial on cardiorespiratory fitness.
      METHODS: A total of 53 10- to 13-year-old children from one public school were
      included. The children were randomised into either a cycling group or a control
      group. The cycling group was encouraged to cycle to and from school each day
      during a period of 12 weeks. Peak oxygen consumption (VO(2peak)) and
      anthropometrical data (weight and height) were measured at baseline and at the
      end of the 12-week period. RESULTS: No significant differences were observed in
      VO(2peak) change over the 12-week period between the cycling group and the
      control group (49.7 ml O(2)/min/kg vs. 50.6 ml O(2) /min/kg; effect size=-0.13,
      F=0.495, p=0.486). Within the intervention group, 69.2% (95% CI 50.1-88.2)
      started cycling, and within the control group 40.8% (95% CI 20.9-60.5) started
      cycling. Given that several children in both groups (intervention and control)
      started cycling to school, re-analyses were conducted between those starting
      cycling and those not starting cycling. At follow up, a significant difference
      between those starting cycling and those who did not starting cycling was
      observed in VO(2peak) (51.7 ml O(2)/min/kg vs. 47.9 ml O(2)/min/kg; effect
      size=0.49, F=8.145, p=0.007), after adjustment for baseline scores, gender and
      age. CONCLUSIONS: This study indicates that cycling to school improves
      cardiorespiratory fitness.

PMID- 22637364
TI  - Civil society and public health research in the European Union new member states.
AB  - INTRODUCTION: Civil society organisations (CSOs) are not-for-profit organisations
      working for the public interest with concerns complementary to public health. We
      investigated the contribution of CSOs in public health research. METHODS: Within
      a European project STEPS (Strengthening Engagement with Public Health Research),
      CSOs with interests in health were identified in the new member states of the
      European Union (Estonia, Latvia, Lithuania, Poland, Hungary, Slovakia, Czech
      Republic, Slovenia, Romania, Bulgaria, Malta, and Cyprus) and workshops
      organised, held in their own languages. The reports of the workshops were
      translated into English and drawn together through a framework analysis. RESULTS:
      CSOs can contribute in all stages of the research cycle, through championship,
      priority-setting, capacity building and generation of resources, sharing and
      application of the research results, and dissemination across their network of
      contacts. There have been successful CSO-researcher collaborations in public
      health fields. Funding is important, and ministries of health and public
      institutions should interact more with CSOs. Barriers include attitudes,
      technical understanding across public health fields. CONCLUSION: There is little
      European empirical literature linking health CSOs and research: our results
      indicate benefits and further opportunities. In contrast to biomedicine's link
      with industry, public health research can align with civil society in not-for
      profit research. CSOs are important for European integration, and their
      contribution should be better recognised at international level.

PMID- 22637365
TI  - Is there equity in use of healthcare services among immigrants, their
      descendents, and ethnic Danes?
AB  - BACKGROUND: Legislation in Denmark explicitly states the right to equal access to
      healthcare. Nevertheless, inequities may exist; accordingly evidence is needed.
      Our objective was to investigate whether differences in healthcare utilisation in
      immigrants, their descendents, and ethnic Danes could be explained by health
      status, socioeconomic factors, and integration. METHODS: We conducted a
      nationwide survey in 2007 with 4952 individuals aged 18-66 comprising ethnic
      Danes; immigrants from the former Yugoslavia, Iran, Iraq, Lebanon, Pakistan,
      Somalia, Turkey; and Turkish and Pakistani descendents. Data were linked to
      registries on healthcare utilisation. Using Poisson regression models, contacts
      to hospital, emergency room (ER), general practitioner (GP), specialist in
      private practice, and dentist were estimated. Analyses were adjusted for health
      symptoms, sociodemographic factors, and proxies of integration. RESULTS: In
      adjusted analyses, immigrants and their descendents had increased use of ER
      (multiplicative effect 1.19-5.02 dependent on immigrant and descendent group) and
      less frequent contact to dentist (multiplicative effect 0.04-0.80 dependent on
      the group). For hospitalisation, GP, and specialist doctor, physical health
      symptoms had positive but different explanatory effects within groups; however,
      most immigrant and descendent groups had increased use of services compared with
      that of ethnic Danes. Socioeconomic factors and integration had no systematic
      effect on the use in the different groups. CONCLUSIONS: The Danish healthcare
      system seems responsive to health across different population groups. We found no
      systematic pattern of inequity in use of free-of-charge healthcare services, but
      for dentists, who require co-payment, we found inequity among immigrants and
      descendents compared with ethnic Danes.

PMID- 22637366
TI  - Perception of overweight and obesity from different angles: a qualitative study.
AB  - AIMS: Up to this date, the obesity pandemic has yet to be confined, with
      prevalence rates still rising in most countries. Aside from numerous negative
      consequences such as comorbid diseases and a reduction in life expectancy due to
      excessive bodyweight and the economic impact of obesity on healthcare systems,
      negative outcomes in overweight and obese individuals are also affected by
      perceived stigmatisation and discrimination. Knowledge of common views and
      perception overweight and obesity in the general public as well as in specific
      populations (e.g. healthcare professionals) is crucial in order to develop stigma
      reduction interventions. The specific aim of the current study was to develop an
      appropriate questionnaire to be used in the survey to follow and further to
      enhance existing instruments. METHODS: This qualitative study reports results
      from focus groups with normal-weight and overweight individuals as well as
      healthcare professionals. RESULTS: Contents of the discussion of overweight and
      obesity did not differ substantially between the three groups. Results show that
      the definition of obesity in our focus groups is a subjective construct
      influenced mainly by aesthetics, sympathy, and activity. Within the groups,
      obesity was mainly seen as a controllable condition; however, external, such as
      societal, factors were named as well. In line with this and as expected from
      theoretical background, obese individuals are ascribed mainly negative
      attributions. CONCLUSIONS: With these results, this study enlightens lived
      realities of different groups of people. The results can be applied to improve
      existing instruments for the measurement of attitudes towards obesity.

PMID- 22637367
TI  - Will sick leave after a counselling intervention prevent later burnout? A 3-year
      follow-up study of Norwegian doctors.
AB  - INTRODUCTION: Burnout and mental distress in working doctors increase the risk
      for both suboptimal treatment of patients and negative health consequences for
      the doctors. Doctors have low rates of sickness absence and are reluctant to seek
      help, especially for mental distress. We examined whether a spell of sickness
      absence after a counselling intervention could predict reduction in emotional
      exhaustion among doctors at work 3 years later. METHODS: A 3-year follow up after
      a counselling intervention for burnout at the Resource Centre Villa Sana in
      Norway in 2003-05 was completed by 184/227 doctors. Self-report assessments were
      administered at baseline, 1-, and 3-years. The effect of number of weeks of
      sickness absence on reduction in emotional exhaustion among doctors working 3
      years after the intervention was assessed by linear regression. RESULTS: Of the
      184 doctors completing assessment, 149 were working at 3-year follow up.
      Emotional exhaustion (scale 1-5) was significantly reduced at follow up (from
      3.00+/-0.96 to 2.37+/-0.79, p<0.001). The number of weeks of sickness absence
      after the intervention was a significant positive predictor of this reduction
      (beta=0.31, p<0.001), also after including sex, age, neuroticism, reduction of
      work hours, and other forms for treatment in the model. CONCLUSIONS: The number
      of weeks of sickness absence after a counselling intervention for burnout had a
      positive predictive effect on reduction in emotional exhaustion among doctors at
      work 3 years later. Sick leave thus seems to "prevent" later burnout, which can
      be of importance both for their patients and for the doctors themselves.

PMID- 22637368
TI  - Socially differentiated cardiac rehabilitation: can we improve referral,
      attendance and adherence among patients with first myocardial infarction?
AB  - AIM: The comprehensive cardiac rehabilitation (CR) programme after myocardial
      infarction (MI) improves quality of life and results in reduced cardiac mortality
      and recurrence of MI. Hospitals worldwide face problems with low participation
      rates in rehabilitation programmes. Inequality in recruitment and participation
      among low educated and socially vulnerable patients must be addressed to lower
      inequality in post-MI health. Our aim was to improve referral, attendance, and
      adherence rates among socially vulnerable patients by systematic screening and by
      offering a socially differentiated cardiac rehabilitation programme. METHODS:
      From 1 September 2002 to 31 December 2005, 388 first-incidence MI patients <=75
      years were hospitalised. Register check for newly hospitalised MI patients,
      screening interview, and systematic referral were conducted by a project nurse.
      Patients were referred to a standard rehabilitation programme (SRP). If patients
      were identified as socially vulnerable, they were offered an extended version of
      the rehabilitation programme (ERP). Excluded patients were offered home visits by
      a cardiac nurse. Concordance principles were used in the individualised programme
      elements. Adherence was registered until the 1-year follow up. RESULTS: 86% were
      referred to the CR. A large share of elderly patients and women were excluded.
      The attendance and adherence rates were 80% and 71%, respectively among all
      hospitalised patients. Among referred patients, the attendance rate was 93%.
      Patients were equally distributed to the SRP and the ERP. No inequality was found
      in attendance and adherence among referred patients. CONCLUSIONS: It seems
      possible to overcome unequal referral, attendance, and adherence in cardiac
      rehabilitation by organisation of systematic screening and social
      differentiation.

PMID- 22637372
TI  - Registration of surgical adverse outcomes: a reliability study in a university
      hospital.
AB  - OBJECTIVE: Accurate registration of adverse surgical outcomes is essential to
      detect areas for improvement of surgical care quality. One reason for inaccurate
      adverse outcome registration may be the method to collect these outcomes. The
      authors compared the completeness of the national complication registry database
      (LHCR) as used in our hospital with relevant information from other available
      resources. DESIGN: Retrospective reliability analysis. SETTING: University
      hospital. PARTICIPANTS: From the 3252 patients admitted to the surgical wards in
      2010, the authors randomly selected a cohort of 180 cases, oversampling those
      with adverse outcomes. The LHCR contains adverse outcomes as reported during
      morning hand-offs or in discharge letters. The authors checked if the number and
      severity of adverse outcomes recorded in the LHCR agreed with those reported in
      morning hand-offs, discharge letters and medical and nursing files. RESULTS: In
      135 of 180 patients, all resources could be retrieved completely. Fourteen per
      cent of the patients with adverse outcomes were not recorded in the LHCR. Missing
      adverse outcomes were all reversible without the need for (re)operation, for
      example, postoperative pain, delirium or urinary tract complications. Only 38% of
      these adverse outcomes were reported in the morning hand-offs and discharge
      letters but were best reported in the medical and nursing files. CONCLUSIONS:
      Registration of surgical adverse outcomes appears largely depending on the
      reliability of the underlying sources. For a more complete adverse outcome
      registration, the authors advocate a better hand-off and additional consultation
      of the patient's dossier. This extra effort allows for improvement actions to
      eventually avoid 'mild' adverse outcomes patients perceive as important and
      undesirable.

PMID- 22637373
TI  - Impact of a pharmacist-prepared interim residential care medication
      administration chart on gaps in continuity of medication management after
      discharge from hospital to residential care: a prospective pre- and post
      intervention study (MedGap Study).
AB  - OBJECTIVES: To test the impact of a hospital pharmacist-prepared interim
      residential care medication administration chart (IRCMAC) on medication
      administration errors and use of locum medical services after discharge from
      hospital to residential care. DESIGN: Prospective pre-intervention and post
      intervention study. SETTING: One major acute care hospital and one subacute aged
      care hospital; 128 residential care facilities (RCF) in Victoria, Australia.
      PARTICIPANTS: 428 patients (median age 84 years, IQR 79-88) discharged to a RCF
      from an inpatient ward over two 12-week periods. INTERVENTION: Seven-day IRCMAC
      auto-populated with patient and medication data from the hospitals' pharmacy
      dispensing software, completed and signed by a hospital pharmacist and sent with
      the patient to the RCF. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary end
      points were the proportion of patients with one or more missed or significantly
      delayed (>50% of prescribed dose interval) medication doses, and the proportion
      of patients whose RCF medication chart was written by a locum doctor, in the 24 h
      after discharge. Secondary end points included RCF staff and general
      practitioners' opinions about the IRCMAC. RESULTS: The number of patients who
      experienced one or more missed or delayed doses fell from 37/202 (18.3%) to 6/226
      (2.7%) (difference in percentages 15.6%, 95% CI 9.5% to 21.9%, p<0.001). The
      number of patients whose RCF medication chart was written by a locum doctor fell
      from 66/202 (32.7%) to 25/226 (11.1%) (difference in percentages 21.6%, 95% CI
      13.5% to 29.7%, p<0.001). For 189/226 (83.6%) discharges, RCF staff reported that
      the IRCMAC improved continuity of care; 31/35 (88.6%) general practitioners said
      that the IRCMAC reduced the urgency for them to attend the RCF and 35/35 (100%)
      said that IRCMACs should be provided for all patients discharged to a RCF.
      CONCLUSIONS: A hospital pharmacist-prepared IRCMAC significantly reduced
      medication errors and use of locum medical services after discharge from hospital
      to residential care.

PMID- 22637374
TI  - Social differences in lung cancer management and survival in South East England:
      a cohort study.
AB  - OBJECTIVE: To examine possible social variations in lung cancer survival and
      assess if any such gradients can be attributed to social differences in
      comorbidity, stage at diagnosis or treatment. DESIGN: Population-based cohort
      identified in the Thames Cancer Registry. SETTING: South East England.
      PARTICIPANTS: 15 582 lung cancer patients diagnosed between 2006 and 2008. MAIN
      OUTCOME MEASURES: Stage at diagnosis, surgery, radiotherapy, chemotherapy and
      survival. RESULTS: The likelihood of being diagnosed as having early-stage
      disease did not vary by socioeconomic quintiles (p=0.58). In early-stage non
      small-cell lung cancer, the likelihood of undergoing surgery was lowest in the
      most deprived group. There were no socioeconomic differences in the likelihood of
      receiving radiotherapy in stage III disease, while in advanced disease and in
      small-cell lung cancer, receipt of chemotherapy differed over socioeconomic
      quintiles (p<0.01). In early-stage disease and following adjustment for
      confounders, the HR between the most deprived and the most affluent group was
      1.24 (95% CI 0.98 to 1.56). Corresponding estimates in stage III and advanced
      disease or small-cell lung cancer were 1.16 (95% CI 1.01 to 1.34) and 1.12 (95%
      CI 1.05 to 1.20), respectively. In early-stage disease, the crude HR between the
      most deprived and the most affluent group was approximately 1.4 and constant
      through follow-up, while in patients with advanced disease or small-cell lung
      cancer, no difference was detectable after 3 months. CONCLUSION: We observed
      socioeconomic variations in management and survival in patients diagnosed as
      having lung cancer in South East England between 2006 and 2008, differences which
      could not fully be explained by social differences in stage at diagnosis, co
      morbidity and treatment. The survival observed in the most affluent group should
      set the target for what is achievable for all lung cancer patients, managed in
      the same healthcare system.

PMID- 22637375
TI  - The economic benefit of hip replacement: a 5-year follow-up of costs and outcomes
      in the Exeter Primary Outcomes Study.
AB  - OBJECTIVES: To assess changes in quality of life and costs of patients undergoing
      primary total hip replacement using the Exeter prosthesis compared with a
      hypothetical 'no surgery' group. DESIGN: The incremental quality of life, quality
      adjusted life years (QALYs) and cost of Exeter Primary Outcomes Study patients
      was compared with hypothetical 'no surgery' group over 5 years. Scores from
      annual SF-36 assessments were converted into utility scores using an established
      algorithm and the QALY gains calculated from pre-operative baseline scores. Costs
      included implant costs and length of stay. SETTING: Secondary care hospitals.
      PARTICIPANTS: Patients receiving a primary Exeter implant enrolled in five of
      seven Exeter Primary Outcomes Study centres. RESULTS: On average, patients gained
      around 0.8 QALYs over 5 years. Younger and male patients or those with lower body
      mass index and poorer Oxford Hip Scores were significantly associated with
      increased QALYs. Treatment costs for a primary episode of care were just over
      L5000 (95% CI L4588 to L5812) per patient. Compared with 'no surgery', the cost
      per QALY was L7182 (95% CI L6470 to L7678), and this remained stable when key
      cost parameters were varied. The most likely cost per QALY was between L7058 and
      L7220. Older patients (age 75+) cost more, mainly due to longer average hospital
      stays and had a higher cost per QALY, although this remained below L10 000.
      CONCLUSIONS: 85% of cases had a cost of <L20 000 per QALY (with 70% having a cost
      per QALY under L10 000) compared with no surgery. Cases would be considered cost
      effective under currently accepted thresholds (L25 000-L30 000) compared with 'no
      surgery'. However, depending on age and severity, younger patients and more
      severe patients had below average cost per QALYs. These results help to confirm
      the long-term benefits and cost-effectiveness of total hip replacement in a wide
      variety of patients using well-established implant models such as the Exeter.
      However, further and ongoing economic appraisal of this and other models is
      required for comparative purposes.

PMID- 22637376
TI  - Detailed protocol for the lifestyle intervention in the BeWEL randomised
      controlled trial of weight loss in adults who have had a colorectal adenoma.
AB  - INTRODUCTION: The BeWEL study is aimed at assessing the impact of a personalised
      lifestyle programme on body weight in people at risk of developing colorectal
      adenomas. The study is a two-arm multicentre randomised controlled trial
      comparing the BeWEL lifestyle programme against usual care. Over 12 months, 316
      people who have had a colorectal adenoma removed through the national screening
      programme will be randomised to provide 80% power to detect a weight loss
      (primary outcome) of 7% over 12 months. METHODS: The 12-month intervention will
      be delivered by lifestyle counsellors via three face-to-face visits followed by
      nine monthly telephone support calls. Consultant endorsement for the study will
      be stressed. An individualised caloric prescription based on estimates for weight
      maintenance -600 kcal will be calculated. Motivational interviewing techniques
      will be used to identify personal motivations for weight change and ways to
      improve perceived self-efficacy. The programme will utilise personalised diet and
      physical activity data from baseline measures to set behavioural goals. A range
      of behavioural strategies will be employed to support lifestyle change including
      goal setting, identifying specific implementation intentions, self-monitoring and
      feedback. Emphasis will be placed on self-monitoring body weight, and weighing
      scales will be provided. Programme acceptability will be explored
      postintervention with indepth interviews. Compliance and impact will be assessed
      by baseline and follow-up measures of diet by self-report, activity by
      accelerometry and anthropometry. ETHICS AND DISSEMINATION: Ethical approval has
      been obtained from the Tayside Committee on Medical Research Ethics.
      Dissemination of results will focus on publications in peer-reviewed journals,
      presentations at national/international cancer meetings and NHS groups. In
      addition, the work will be communicated to the public through forums such at The
      Scottish Cancer Prevention Network (http://www.cancerpreventionscotland.co.uk/).
      The trial is registered with Current Controlled Trials (International Standard
      Randomised Controlled Trials No: ISRCTN53033856).

PMID- 22637429
TI  - C9ORF72 repeat expansion in amyotrophic lateral sclerosis in the Kii peninsula of
      Japan.
AB  - BACKGROUND: In the Kii peninsula of Japan, high prevalences of amyotrophic
      lateral sclerosis (ALS) and parkinsonism-dementia complex have been reported.
      There are 2 major foci with a high prevalence, which include the southernmost
      region neighboring the Koza River (Kozagawa and Kushimoto towns in Wakayama
      prefecture) and the Hohara district (Mie prefecture). OBJECTIVE: To delineate the
      molecular basis of ALS in the Kii peninsula of Japan, we analyzed hexanucleotide
      repeat expansion in the chromosome 9 open reading frame 72 (C9ORF72) gene, which
      has recently been identified as a frequent cause of ALS and frontotemporal
      dementia in the white population. DESIGN: Case series. SETTING: University
      hospitals. PATIENTS: Twenty-one patients (1 familial patient and 20 sporadic
      patients) with ALS from Wakayama prefecture, and 16 patients with ALS and 16
      patients with parkinsonism-dementia complex originating from Mie prefecture
      surveyed in 1994 through 2011 were enrolled in the study. In addition, 40
      probands with familial ALS and 217 sporadic patients with ALS recruited from
      other areas of Japan were also enrolled in this study. MAIN OUTCOME MEASURES:
      After screening by repeat-primed polymerase chain reaction, Southern blot
      hybridization analysis was performed to confirm the expanded alleles. RESULTS: We
      identified 3 patients with ALS (20%) with the repeat expansion in 1 of the 2
      disease foci. The proportion is significantly higher than those in other regions
      in Japan. Detailed haplotype analyses revealed an extended shared haplotype in
      the 3 patients with ALS, suggesting a founder effect. CONCLUSIONS: Our findings
      indicate that the repeat expansion partly accounts for the high prevalence of ALS
      in the Kii peninsula.

PMID- 22637471
TI  - Characterization of a family with c9FTD/ALS associated with the GGGGCC repeat
      expansion in C9ORF72.
AB  - BACKGROUND: The hexanucleotide repeat in the chromosome 9 open reading frame 72
      (C9ORF72) gene was recently discovered as the underlying genetic cause of many
      families with frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis
      (ALS) linked to chromosome 9 (c9FTD/ALS). We report the clinical,
      neuropsychologic, and neuroimaging findings of a family with the C9ORF72 mutation
      and clinical diagnoses bridging the FTD, parkinsonism, and ALS spectrum.
      OBJECTIVE: To characterize the antemortem characteristics of a family with
      c9FTD/ALS associated with the GGGGCC repeat expansion in C9ORF72. DESIGN:
      Clinical series. SETTING: Tertiary care academic medical center. PATIENTS The
      members of a family affected by the mutation with features of FTD and/or ALS.
      MAIN OUTCOME MEASURES: Clinical, neuropsychologic, and neuroimaging assessments.
      RESULTS: All 3 examined subjects had the hexanucleotide expansion detected in
      C9ORF72. All had personality/behavioral changes early in the course of the
      disease. One case had levodopa-unresponsive parkinsonism, and 1 had ALS. Magnetic
      resonance imaging showed symmetric bilateral frontal, temporal, insular, and
      cingulate atrophy. CONCLUSIONS: This report highlights the clinical and
      neuroimaging characteristics of a family with c9FTD/ALS. Further studies are
      needed to better understand the phenotypical variability and the
      cliniconeuroimaging-neuropathologic correlations.

PMID- 22637472
TI  - Longitudinal data analysis with non-ignorable missing data.
AB  - A common problem in the longitudinal data analysis is the missing data problem.
      Two types of missing patterns are generally considered in statistical literature:
      monotone and non-monotone missing data. Nonmonotone missing data occur when study
      participants intermittently miss scheduled visits, while monotone missing data
      can be from discontinued participation, loss to follow-up, and mortality.
      Although many novel statistical approaches have been developed to handle missing
      data in recent years, few methods are available to provide inferences to handle
      both types of missing data simultaneously. In this article, a latent random
      effects model is proposed to analyze longitudinal outcomes with both monotone and
      non-monotone missingness in the context of missing not at random. Another
      significant contribution of this article is to propose a new computational
      algorithm for latent random effects models. To reduce the computational burden of
      high-dimensional integration problem in latent random effects models, we develop
      a new computational algorithm that uses a new adaptive quadrature approach in
      conjunction with the Taylor series approximation for the likelihood function to
      simplify the E-step computation in the expectation-maximization algorithm.
      Simulation study is performed and the data from the scleroderma lung study are
      used to demonstrate the effectiveness of this method. 

PMID- 22637473
TI  - Critical determinants of human alpha-defensin 5 activity against non-enveloped
      viruses.
AB  - Human alpha-defensins, such as human alpha-defensin 5 (HD5), block infection of
      non-enveloped viruses, including human adenoviruses (AdV), papillomaviruses
      (HPV), and polyomaviruses. Through mutational analysis of HD5, we have identified
      arginine residues that contribute to antiviral activity against AdV and HPV. Of
      two arginine residues paired on one face of HD5, Arg-28 is critical for both
      viruses, while Arg-9 is only important for AdV. Two arginine residues on the
      opposite face of the molecule (Arg-13 and Arg-32) and unpaired Arg-25 are less
      important for both. In addition, hydrophobicity at residue 29 is a major
      determinant of anti-adenoviral activity, and a chemical modification that
      prevents HD5 self-association was strongly attenuating. Although HD5 binds to the
      capsid of AdV, the molecular basis for this interaction is undefined. Capsid
      binding by HD5 is not purely charge-dependent, as substitution of lysine for Arg
      9 and Arg-28 was deleterious. Analysis of HD5 analogs that retained varying
      levels of potency demonstrated that anti-adenoviral activity is directly
      correlated with HD5 binding to the virus, confirming that the viral capsid rather
      than the cell is the relevant target. Also, AdV aggregation induced by HD5
      binding is not sufficient for neutralization. Rather, these studies confirm that
      the major mechanism of HD5-mediated neutralization of AdV depends upon specific
      binding to the viral capsid through interactions mediated in part by critical
      arginine residues, hydrophobicity at residue 29, and multimerization of HD5,
      which increases initial binding of virus to the cell but prevents subsequent
      viral uncoating and genome delivery to the nucleus.

PMID- 22637474
TI  - Investigating substrate promiscuity in cyclooxygenase-2: the role of Arg-120 and
      residues lining the hydrophobic groove.
AB  - The cyclooxygenases (COX-1 and COX-2) generate prostaglandin H(2) from
      arachidonic acid (AA). In its catalytically productive conformation, AA binds
      within the cyclooxygenase channel with its carboxylate near Arg-120 and Tyr-355
      and omega-end located within a hydrophobic groove above Ser-530. Although AA is
      the preferred substrate for both isoforms, COX-2 can oxygenate a broad spectrum
      of substrates. Mutational analyses have established that an interaction of the
      carboxylate of AA with Arg-120 is required for high affinity binding by COX-1 but
      not COX-2, suggesting that hydrophobic interactions between the omega-end of
      substrates and cyclooxygenase channel residues play a significant role in COX-2
      mediated oxygenation. We used structure-function analyses to investigate the role
      that Arg-120 and residues lining the hydrophobic groove play in the binding and
      oxygenation of substrates by murine (mu) COX-2. Mutations to individual amino
      acids within the hydrophobic groove exhibited decreased rates of oxygenation
      toward AA with little effect on binding. R120A muCOX-2 oxygenated 18-carbon omega
      6 and omega-3 substrates albeit at reduced rates, indicating that an interaction
      with Arg-120 is not required for catalysis. Structural determinations of Co(3+)
      protoporphyrin IX-reconstituted muCOX-2 with alpha-linolenic acid and G533V muCOX
      2 with AA indicate that proper bisallylic carbon alignment is the major
      determinant for efficient substrate oxygenation by COX-2. Overall, these findings
      implicate Arg-120 and hydrophobic groove residues as determinants that govern
      proper alignment of the bisallylic carbon below Tyr-385 for catalysis in COX-2
      and confirm nuances between COX isoforms that explain substrate promiscuity.

PMID- 22637475
TI  - Mesencephalic astrocyte-derived neurotrophic factor protects the heart from
      ischemic damage and is selectively secreted upon sarco/endoplasmic reticulum
      calcium depletion.
AB  - The endoplasmic reticulum (ER) stress protein mesencephalic astrocyte-derived
      neurotrophic factor (MANF) has been reported to protect cells from stress-induced
      cell death before and after its secretion; however, the conditions under which it
      is secreted are not known. Accordingly, we examined the mechanism of MANF release
      from cultured ventricular myocytes and HeLa cells, both of which secrete proteins
      via the constitutive pathway. Although the secretion of proteins via the
      constitutive pathway is not known to increase upon changes in intracellular
      calcium, MANF secretion was increased within 30 min of treating cells with
      compounds that deplete sarcoplasmic reticulum (SR)/ER calcium. In contrast,
      secretion of atrial natriuretic factor from ventricular myocytes was not
      increased by SR/ER calcium depletion, suggesting that not all secreted proteins
      exhibit the same characteristics as MANF. We postulated that SR/ER calcium
      depletion triggered MANF secretion by decreasing its retention. Consistent with
      this were co-immunoprecipitation and live cell, zero distance, photo affinity
      cross-linking, demonstrating that, in part, MANF was retained in the SR/ER via
      its calcium-dependent interaction with the SR/ER-resident protein, GRP78 (glucose
      regulated protein 78 kDa). This unusual mechanism of regulating secretion from
      the constitutive secretory pathway provides a potentially missing link in the
      mechanism by which extracellular MANF protects cells from stresses that deplete
      SR/ER calcium. Consistent with this was our finding that administration of
      recombinant MANF to mice decreased tissue damage in an in vivo model of
      myocardial infarction, a condition during which ER calcium is known to be
      dysregulated, and MANF expression is induced.

PMID- 22637476
TI  - Mechanism for p38alpha-mediated experimental autoimmune encephalomyelitis.
AB  - One of the mitogen-activated protein kinases, p38, has been found to play a
      crucial role in various inflammatory responses. In this study, we analyzed the
      roles of p38alpha in multiple sclerosis, using an animal model, experimental
      autoimmune encephalomyelitis (EAE). p38alpha(+/-) mice (p38alpha(-/-) showed
      embryonic lethality) showed less severe neurological signs than WT mice. Adoptive
      transfer of lymph node cells (LNC) from sensitized WT mice with MOG(35-55) to
      naive WT-induced EAE was much more severe compared with the case using LNC from
      sensitized p38alpha(+/-) mice. Comprehensive analysis of cytokines from MOG(35
      55)-challenged LNC by Western blot array revealed that production of IL-17 was
      significantly reduced by a single copy disruption of the p38alpha gene or a p38
      inhibitor. Likewise, by a luciferase reporter assay, an electrophoresis mobility
      shift assay, and characterization of the relationship between p38 activity and IL
      17 mRNA expression, we confirmed that p38 positively regulates transcription of
      the Il17 gene. Furthermore, oral administration of a highly specific p38alpha
      inhibitor (UR-5269) to WT mice at the onset of EAE markedly suppressed the
      progression of EAE compared with a vehicle group. These results suggest that
      p38alpha participates in the pathogenesis of EAE through IL-17 induction.

PMID- 22637477
TI  - Smooth muscle-specific expression of calcium-independent phospholipase A2beta
      (iPLA2beta) participates in the initiation and early progression of vascular
      inflammation and neointima formation.
AB  - Whether group VIA phospholipase A(2) (iPLA(2)beta) is involved in vascular
      inflammation and neointima formation is largely unknown. Here, we report that
      iPLA(2)beta expression increases in the vascular tunica media upon carotid artery
      ligation and that neointima formation is suppressed by genetic deletion of
      iPLA(2)beta or by inhibiting its activity or expression via perivascular delivery
      of bromoenol lactone or of antisense oligonucleotides, respectively. To
      investigate whether smooth muscle-specific iPLA(2)beta is involved in neointima
      formation, we generated transgenic mice in which iPLA(2)beta is expressed
      specifically in smooth muscle cells and demonstrate that smooth muscle-specific
      expression of iPLA(2)beta exacerbates ligation-induced neointima formation and
      enhanced both production of proinflammatory cytokines and vascular infiltration
      by macrophages. With cultured vascular smooth muscle cell, angiotensin II,
      arachidonic acid, and TNF-alpha markedly induce increased expression of IL-6 and
      TNF-alpha mRNAs, all of which were suppressed by inhibiting iPLA(2)beta activity
      or expression with bromoenol lactone, antisense oligonucleotides, and genetic
      deletion, respectively. Similar suppression also results from genetic deletion of
      12/15-lipoxygenase or inhibiting its activity with nordihydroguaiaretic acid or
      luteolin. Expression of iPLA(2)beta protein in cultured vascular smooth muscle
      cells was found to depend on the phenotypic state and to rise upon incubation
      with TNF-alpha. Our studies thus illustrate that smooth muscle cell-specific
      iPLA(2)beta participates in the initiation and early progression of vascular
      inflammation and neointima formation and suggest that iPLA(2)beta may represent a
      novel therapeutic target for preventing cardiovascular diseases.

PMID- 22637479
TI  - Cooperative and stochastic calcium releases from multiple calcium puff sites
      generate calcium microdomains in intact Hela cells.
AB  - Ca(2+) microdomains or locally restricted Ca(2+) increases in the cell have
      recently been reported to regulate many essential physiological events. Ca(2+)
      increases through the inositol 1,4,5-trisphosphate (IP(3)) receptor
      (IP(3)R)/Ca(2+) release channels contribute to the formation of a class of such
      Ca(2+) microdomains, which were often observed and referred to as Ca(2+) puffs in
      their isolated states. In this report, we visualized IP(3)-evoked Ca(2+)
      microdomains in histamine-stimulated intact HeLa cells using a total internal
      reflection fluorescence microscope, and quantitatively characterized the spatial
      profile by fitting recorded images to a two-dimensional Gaussian distribution.
      Ca(2+) concentration profiles were marginally spatially anisotropic, with the
      size increasing linearly even after the amplitude began to decline. We found the
      event centroid drifted with an apparent diffusion coefficient of 4.20 +/- 0.50
      MUm(2)/s, which is significantly larger than those estimated for IP(3)Rs. The
      sites of maximal Ca(2+) increase, rather than initiation or termination sites,
      were detected repeatedly at the same location. These results indicate that Ca(2+)
      microdomains in intact HeLa cell are generated from spatially distributed
      multiple IP(3)R clusters or Ca(2+) puff sites, rather than a single IP(3)R
      cluster reported in cells loaded with Ca(2+) buffers.

PMID- 22637478
TI  - Pseudomonas aeruginosa exotoxin Y is a promiscuous cyclase that increases
      endothelial tau phosphorylation and permeability.
AB  - Exotoxin Y (ExoY) is a type III secretion system effector found in ~ 90% of the
      Pseudomonas aeruginosa isolates. Although it is known that ExoY causes inter
      endothelial gaps and vascular leak, the mechanisms by which this occurs are
      poorly understood. Using both a bacteria-delivered and a codon-optimized
      conditionally expressed ExoY, we report that this toxin is a dual soluble
      adenylyl and guanylyl cyclase that results in intracellular cAMP and cGMP
      accumulation. The enzymatic activity of ExoY caused phosphorylation of
      endothelial Tau serine 214, accumulation of insoluble Tau, inter-endothelial cell
      gap formation, and increased macromolecular permeability. To discern whether the
      cAMP or cGMP signal was responsible for Tau phosphorylation and barrier
      disruption, pulmonary microvascular endothelial cells were engineered for the
      conditional expression of either wild-type guanylyl cyclase, which synthesizes
      cGMP, or a mutated guanylyl cyclase, which synthesizes cAMP. Sodium nitroprusside
      stimulation of the cGMP-generating cyclase resulted in transient Tau serine 214
      phosphorylation and gap formation, whereas stimulation of the cAMP-generating
      cyclase induced a robust increase in Tau serine 214 phosphorylation, gap
      formation, and macromolecular permeability. These results indicate that the cAMP
      signal is the dominant stimulus for Tau phosphorylation. Hence, ExoY is a
      promiscuous cyclase and edema factor that uses cAMP and, to some extent, cGMP to
      induce the hyperphosphorylation and insolubility of endothelial Tau. Because
      hyperphosphorylated and insoluble Tau are hallmarks in neurodegenerative
      tauopathies such as Alzheimer disease, acute Pseudomonas infections cause a
      pathophysiological sequela in endothelium previously recognized only in chronic
      neurodegenerative diseases.

PMID- 22637480
TI  - RUTBC2 protein, a Rab9A effector and GTPase-activating protein for Rab36.
AB  - Rab GTPases regulate vesicle budding, motility, docking, and fusion. In cells,
      their cycling between active, GTP-bound states and inactive, GDP-bound states is
      regulated by the action of opposing enzymes called guanine nucleotide exchange
      factors and GTPase-activating proteins (GAPs). The substrates for most RabGAPs
      are unknown, and the potential for cross-talk between different membrane
      trafficking pathways remains uncharted territory. Rab9A and its effectors
      regulate recycling of mannose 6-phosphate receptors from late endosomes to the
      trans Golgi network. We show here that RUTBC2 is a TBC domain-containing protein
      that binds to Rab9A specifically both in vitro and in cultured cells but is not a
      GAP for Rab9A. Biochemical screening of Rab protein substrates for RUTBC2
      revealed highest GAP activity toward Rab34 and Rab36. In cells, membrane
      associated RUTBC2 co-localizes with Rab36, and expression of wild type RUTBC2,
      but not the catalytically inactive, RUTBC2 R829A mutant, decreases the amount of
      membrane-associated Rab36 protein. These data show that RUTBC2 can act as a Rab36
      GAP in cells and suggest that RUTBC2 links Rab9A function to Rab36 function in
      the endosomal system.

PMID- 22637491
TI  - Socio-demographic and other patient characteristics associated with time between
      colonoscopy and surgery, and choice of treatment centre for colorectal cancer: a
      retrospective cohort study.
AB  - OBJECTIVES: To investigate key patient clinical and demographic characteristics
      associated with time between colonoscopy and surgery, and choice of treatment
      centre for colorectal cancer (CRC) patients. This will add to the little
      published research examining the pathway following CRC diagnosis and prior to
      surgery. DESIGN: Retrospective cohort analysis of linked data. SETTING: A
      population-based sample of people diagnosed August 2004 to December 2007 in New
      South Wales, Australia. PARTICIPANTS: 569 CRC patients, of whom 407 (72%, 95% CI
      68% to 75%) had colonoscopy followed by surgery. PRIMARY OUTCOME MEASURES: Time
      between colonoscopy and surgery, and whether the surgery took place in a
      specialist cancer centre. RESULTS: Among the 407 eligible patients analysed, the
      median time from colonoscopy to surgery was 19 days (IQR 12-29 days). After
      adjusting for key demographic and clinical characteristics such as age and
      disease stage, the time was longer for rectal cancer patients and those reporting
      fair/poor health, although differences in medians were <5 days. 24% (95% CI 20%
      to 28%) had surgery in a specialist cancer centre, which was more common among
      people resident in metropolitan areas (37% vs 14% for others, adjusted p=0.001)
      and those without private health insurance (30% vs 21% for others, adjusted
      p=0.03). CONCLUSIONS: There do not appear to be systemic issues affecting time
      from colonoscopy to surgery related to patients' socio-demographic
      characteristics. However, patients with private insurance and those living in
      rural areas may be less likely to receive optimal specialist treatment. A more
      systematic approach might be needed to ensure cancer patients are treated in
      specialist cancer centres, particularly patients requiring more specialised
      treatment.

PMID- 22637481
TI  - Mechanistic insights into the retaining glucosyl-3-phosphoglycerate synthase from
      mycobacteria.
AB  - Considerable progress has been made in recent years in our understanding of the
      structural basis of glycosyl transfer. Yet the nature and relevance of the
      conformational changes associated with substrate recognition and catalysis remain
      poorly understood. We have focused on the glucosyl-3-phosphoglycerate synthase
      (GpgS), a "retaining" enzyme, that initiates the biosynthetic pathway of
      methylglucose lipopolysaccharides in mycobacteria. Evidence is provided that GpgS
      displays an unusually broad metal ion specificity for a GT-A enzyme, with Mg(2+),
      Mn(2+), Ca(2+), Co(2+), and Fe(2+) assisting catalysis. In the crystal structure
      of the apo-form of GpgS, we have observed that a flexible loop adopts a double
      conformation L(A) and L(I) in the active site of both monomers of the protein
      dimer. Notably, the L(A) loop geometry corresponds to an active conformation and
      is conserved in two other relevant states of the enzyme, namely the
      GpgS.metal.nucleotide sugar donor and the GpgS.metal.nucleotide.acceptor-bound
      complexes, indicating that GpgS is intrinsically in a catalytically active
      conformation. The crystal structure of GpgS in the presence of
      Mn(2+).UDP.phosphoglyceric acid revealed an alternate conformation for the
      nucleotide sugar beta-phosphate, which likely occurs upon sugar transfer.
      Structural, biochemical, and biophysical data point to a crucial role of the beta
      phosphate in donor and acceptor substrate binding and catalysis. Altogether, our
      experimental data suggest a model wherein the catalytic site is essentially
      preformed, with a few conformational changes of lateral chain residues as the
      protein proceeds along the catalytic cycle. This model of action may be
      applicable to a broad range of GT-A glycosyltransferases.

PMID- 22637532
TI  - Membrane-bound Kit ligand regulates melanocyte adhesion and survival, providing
      physical interaction with an intraepithelial niche.
AB  - Morphogenesis, as illustrated by melanocyte migration and homing to the skin,
      requires cadherin adhesion, integrin-dependent migration and Kit-ligand growth
      factor signaling. However, it is not known how Kit ligand regulates integrin or
      cadherin-dependent intraepidermal melanocyte behavior. To answer this question,
      we developed specific 2-dimensional (2D) and 3D culture systems analyzing how
      soluble or immobilized Kit-ligand-regulated melanocyte migration on vitronectin
      and laminin, or within a monolayer of kidney epithelial cells. In a 2D system,
      soluble Kit ligand stimulated integrin-dependent melanoblast migration and
      chemotaxis and accelerated integrin turnover. In contrast, immobilized, but not
      soluble, Kit ligand, enhanced integrin-dependent melanocyte spreading on
      suboptimal laminin concentrations. In 3D, membrane-bound Kit ligand induced
      intraepithelial melanocyte proliferation, survival, and tight adhesion to
      epithelial cells, while cleavable Kit ligand was less effective. In contrast,
      melanocyte motility was independent of membrane-bound Kit ligand, but increased
      in the presence of the cleavable Kit-ligand isoform. Transmembrane-dimerization
      or basolateral-targeting mutants of Kit ligand altered intraepithelial melanocyte
      localization, survival, and adhesion to epithelial cells. These data and the
      identification of c-kit/Kit-ligand clusters at cell contacts suggest that
      membrane-bound Kit ligand captures cell surface-expressed c-kit, providing
      mechanical anchoring and survival signaling within intraepithelial niches, and
      thereby defining a new mechanism for melanocyte homeostasis and requirement for
      environmental niches.

PMID- 22637534
TI  - Beige differentiation of adipose depots in mice lacking prolactin receptor
      protects against high-fat-diet-induced obesity.
AB  - Stimulating conversion of white fat to metabolically active adipocytes (beige
      fat) constitutes a promising strategy against weight gain and its deleterious
      associated-disorders. We provide direct evidence that prolactin (PRL), best known
      for its actions on the mammary gland, plays a pivotal role in energy balance
      through the control of adipocyte differentiation and fate. Here we show that lack
      of prolactin receptor (PRLR) causes resistance to high-fat-diet-induced obesity
      due to enhanced energy expenditure and increased metabolic rate. Mutant mice
      displayed reduced fat mass associated with appearance of massive brown-like
      adipocyte foci in perirenal and subcutaneous but not in gonadal fat depots under
      a high-fat diet. Positron emission tomography imaging further demonstrated the
      occurrence of these thermogenic brown fat depots in adult mice, providing
      additional support for recruitable brown-like adipocytes (beigeing) in white fat
      depots. Consistent with the activation of brown adipose tissue, PRLR inactivation
      increases expression of master genes controlling brown adipocyte fate (PRDM16)
      and mitochondrial function (PGC1alpha, UCP1). Altered pRb/Foxc2 expression
      suggests that this PRL-regulated pathway may contribute to beige cell commitment.
      Together, these results provide direct genetic evidence that PRLR affects energy
      balance and metabolic adaptation in rodents via effects on brown adipose tissue
      differentiation and function.

PMID- 22637533
TI  - Metabolism of circulating ADP in the bloodstream is mediated via integrated
      actions of soluble adenylate kinase-1 and NTPDase1/CD39 activities.
AB  - Extracellular ATP and ADP trigger inflammatory, vasodilatatory, and prothrombotic
      signaling events in the vasculature, and their turnover is governed by networks
      of membrane-associated enzymes. The contribution of soluble activities to
      intravascular nucleotide homeostasis remains controversial. By using thin-layer
      chromatographic assays, we revealed transphosphorylation of [gamma-(32)P]ATP and
      AMP by human and murine sera, which was progressively inhibited by specific
      adenylate kinase (AK) inhibitor Ap(5)A. This phosphotransfer reaction was
      diminished markedly in serum from knockout mice lacking the major AK isoform,
      AK1, and in human serum immunodepleted of AK1. We also showed that ~75% ADP in
      cell-free serum is metabolized via reversible AK1 reaction 2ADP <-> ATP + AMP.
      The generated ATP and AMP are then metabolized through the coupled nucleotide
      pyrophosphatase/phosphodiesterase and 5'-nucleotidase/CD73 reactions,
      respectively. Constitutive presence of another nucleotide-converting enzyme,
      nucleoside triphosphate diphosphohydrolase-1 (NTPDase1, known as CD39), was
      ascertained by the relative deficiency of serum from CD39-null mice to
      dephosphorylate [(3)H]ADP and [gamma-(32)P]ATP, and also by diminished [(3)H]ADP
      hydrolysis by human serum pretreated with NTPDase1 inhibitors, POM-1 and ARL
      67156. In summary, we have identified hitherto unrecognized soluble forms of AK1
      and NTPDase1/CD39 that contribute in the active cycling between the principal
      platelet-recruiting agent ADP and other circulating nucleotides.

PMID- 22637543
TI  - Is the frontal dysexecutive syndrome due to a working memory deficit? Evidence
      from patients with stroke.
AB  - Although frontal dysexecutive disorders are frequently considered to be due to
      working memory deficit, this has not been systematically examined and very little
      evidence is available for impairment of working memory in frontal damage. The
      objective of this study was to examine the components of working memory, their
      anatomy and the relations with executive functions in patients with stroke
      involving the frontal or posterior cortex. The study population consisted of 29
      patients (frontal: n=17; posterior: n=12) and 29 matched controls. Phonological
      loop (letter and word spans, phonological store; rehearsal process), visuospatial
      sketchpad (visuospatial span) and the central executive (working memory span,
      dual task and updating process) were examined. The group comparison analysis
      showed impairment in the frontal group of: (i) verbal spans (P<0.03); (ii) with a
      deficit of the rehearsal process (P=0.006); (iii) visuospatial span (P=0.04);
      (iv) working memory span (P=0.001) that disappeared after controlling for verbal
      span and (v) running memory (P=0.05) unrelated to updating conditions. The
      clinical anatomical correlation study showed that impairment of the central
      executive depended on frontal and posterior lesion. Cognitive dysexecutive
      disorders were observed in 11/20 patients with central executive deficit and an
      inverse dissociation was observed in two patients. Receiver operating
      characteristic curve analysis indicated that cognitive dysexecutive disorders had
      the highest ability to discriminate frontal lesions (area under curve=0.844, 95%
      confidence interval: 0.74-0.95; P=0.0001; central executive impairment: area
      under curve=0.732, 95% confidence interval: 0.57-0.82; P=0.006). This study
      reveals that frontal lesions induce mild impairment of short-term memory
      associated with a deficit of the rehearsal process supporting the role of the
      frontal lobe in this process; the central executive depends on lesions in the
      frontal lobe and posterior regions accounting for its low frequency and the
      negative results of group studies. Finally, the frontal dysexecutive syndrome
      cannot be attributed to central executive impairment, although it may contribute
      to some dysexecutive disorders.

PMID- 22637544
TI  - Is misery perfusion still a predictor of stroke in symptomatic major cerebral
      artery disease?
AB  - Studies in the 1990s demonstrated that misery perfusion is a predictor of
      subsequent stroke in medically treated patients with symptomatic major cerebral
      artery disease. A recent randomized controlled trial demonstrated no benefit of
      bypass surgery for such patients. In this light, outcome in patients with misery
      perfusion has regained interest. The purpose of this study was to determine
      whether misery perfusion is still a predictor of subsequent stroke despite recent
      improvements in medical treatment for secondary prevention of stroke, and if so,
      whether the predictive value of misery perfusion has changed in recent years. We
      prospectively studied 165 non-disabled patients with symptomatic atherosclerotic
      internal carotid artery or middle cerebral artery occlusive diseases who
      underwent positron emission tomography from 1999 to 2008. Misery perfusion was
      defined as decreased cerebral blood flow, increased oxygen extraction fraction
      and decreased ratio of cerebral blood flow to blood volume in the hemisphere
      supplied by the diseased artery. All patients were followed up for 2 years until
      stroke recurrence or death. Bypass surgery was performed in 19 of 35 patients
      with and 16 of 130 patients without misery perfusion. The 2-year incidence of
      ipsilateral ischaemic stroke was six and four patients with and without misery
      perfusion, including two and one after surgery, respectively (P < 0.002). Total
      strokes occurred in nine patients with misery perfusion and 12 patients without
      (P < 0.01). The relative risk conferred by misery perfusion in whole sample was
      6.3 (95% confidence interval 1.7-22.4, P < 0.005) for ipsilateral ischaemic
      stroke and 3.5 (95% confidence interval 1.4-8.9, P < 0.01) for all strokes, while
      the respective values in medically treated patients were 12.6 (95% confidence
      interval 2.7-57.8, P < 0.005) and 4.7 (95% confidence interval 1.3-16.3, P <
      0.02). The all-stroke incidence in patients entering the study from 2004 to 2008
      (4/72) was significantly lower than in those entering from 1999 to 2003 (17/93; P
      < 0.02), although the prevalence of misery perfusion or bypass surgery did not
      differ. Between these periods, patients without misery perfusion demonstrated a
      decrease in stroke rate (from 16.2% to 0%), but patients with misery perfusion
      did not (26.3 and 25.0%). In symptomatic major cerebral artery disease, misery
      perfusion remains a predictor of subsequent stroke, although the recurrence rate
      was lower than the previous study. In patients without misery perfusion, the risk
      of stroke was reduced over time. Thus, identification and stricter management of
      patients with misery perfusion are essential to further improve prognosis.

PMID- 22637575
TI  - Aflatoxin M1 determination in yoghurt produced in Guilan province of Iran using
      immunoaffinity column and high-performance liquid chromatography.
AB  - The present study was aimed to determine the presence and levels of aflatoxin
      M(1) (AFM(1)) in 120 natural yoghurt samples consisting of 80 samples of
      commercial and 40 samples of traditional yoghurt in Guilan province in the north
      of Iran. The occurrence and concentration range of AFM(1) in samples were
      determined by immunoaffinity column extraction and high-performance liquid
      chromatography. Analysis of yoghurts showed that all the samples were
      contaminated with AFM(1) in concentration levels ranging from 4.2 to 78.9 ng/kg.
      In general, 16 samples (13.33%) had higher AFM(1) level than the maximum
      tolerance limit (50 ng/kg) accepted by European Union, but the contamination
      level was lower than 500 ng/kg in all the samples, which is accepted by Codex
      Alimentarius and National Standard. The concentration of AFM(1) in 26 samples
      (21.66) was lower than 10 ng/kg. The range of contamination of AFM(1) was
      comparatively higher in traditional yoghurt (average concentration of 32.9 ng/kg)
      than that in commercial yoghurt (average concentration of 21.6 ng/kg; p < 0.01).
      Because yoghurt is the most popular dairy product consumed in Iran, the AFM(1)
      contamination is a serious problem for public health. This study reports the data
      of a first survey on the presence of AFM1 in yoghurt in Guilan, Iran.

PMID- 22637570
TI  - Integrative analysis of genome-wide loss of heterozygosity and monoallelic
      expression at nucleotide resolution reveals disrupted pathways in triple-negative
      breast cancer.
AB  - Loss of heterozygosity (LOH) and copy number alteration (CNA) feature prominently
      in the somatic genomic landscape of tumors. As such, karyotypic aberrations in
      cancer genomes have been studied extensively to discover novel oncogenes and
      tumor-suppressor genes. Advances in sequencing technology have enabled the cost
      effective detection of tumor genome and transcriptome mutation events at single
      base-pair resolution; however, computational methods for predicting segmental
      regions of LOH in this context are not yet fully explored. Consequently, whole
      transcriptome, nucleotide-level resolution analysis of monoallelic expression
      patterns associated with LOH has not yet been undertaken in cancer. We developed
      a novel approach for inference of LOH from paired tumor/normal sequence data and
      applied it to a cohort of 23 triple-negative breast cancer (TNBC) genomes.
      Following extensive benchmarking experiments, we describe the nucleotide
      resolution landscape of LOH in TNBC and assess the consequent effect of LOH on
      the transcriptomes of these tumors using RNA-seq-derived measurements of allele
      specific expression. We show that the majority of monoallelic expression in the
      transcriptomes of triple-negative breast cancer can be explained by genomic
      regions of LOH and establish an upper bound for monoallelic expression that may
      be explained by other tumor-specific modifications such as epigenetics or
      mutations. Monoallelically expressed genes associated with LOH reveal that cell
      cycle, homologous recombination and actin-cytoskeletal functions are putatively
      disrupted by LOH in TNBC. Finally, we show how inference of LOH can be used to
      interpret allele frequencies of somatic mutations and postulate on temporal
      ordering of mutations in the evolutionary history of these tumors.

PMID- 22637576
TI  - Lecithin:retinol acyltransferase is critical for cellular uptake of vitamin A
      from serum retinol-binding protein.
AB  - Vitamin A (all-trans-retinol) must be adequately distributed within the mammalian
      body to produce visual chromophore in the eyes and all-trans-retinoic acid in
      other tissues. Vitamin A is transported in the blood bound to retinol-binding
      protein (holo-RBP), and its target cells express an RBP receptor encoded by the
      Stra6 (stimulated by retinoic acid 6) gene. Here we show in mice that cellular
      uptake of vitamin A from holo-RBP depends on functional coupling of STRA6 with
      intracellular lecithin:retinol acyltransferase (LRAT). Thus, vitamin A uptake
      from recombinant holo-RBP exhibited by wild type mice was impaired in Lrat(-/-)
      mice. We further provide evidence that vitamin A uptake is regulated by all-trans
      retinoic acid in non-ocular tissues of mice. When in excess, vitamin A was
      rapidly taken up and converted to its inert ester form in peripheral tissues,
      such as lung, whereas in vitamin A deficiency, ocular retinoid uptake was
      favored. Finally, we show that the drug fenretinide, used clinically to
      presumably lower blood RBP levels and thus decrease circulating retinol, targets
      the functional coupling of STRA6 and LRAT to increase cellular vitamin A uptake
      in peripheral tissues. These studies provide mechanistic insights into how
      vitamin A is distributed to peripheral tissues in a regulated manner and identify
      LRAT as a critical component of this process.

PMID- 22637577
TI  - Subunit Interactions and cooperativity in the microtubule-severing AAA ATPase
      spastin.
AB  - Spastin is a hexameric ring AAA ATPase that severs microtubules. To see whether
      the ring complex funnels the energy of multiple ATP hydrolysis events to the site
      of mechanical action, we investigate here the cooperativity of spastin. Several
      lines of evidence indicate that interactions among two subunits dominate the
      cooperative behavior: (i) the ATPase activity shows a sigmoidal dependence on the
      ATP concentration; (ii) ATPgammaS displays a mixed-inhibition behavior for normal
      ATP turnover; and (iii) inactive mutant subunits inhibit the activity of spastin
      in a hyperbolic dependence, characteristic for two interacting species. A
      quantitative model based on neighbor interactions fits mutant titration
      experiments well, suggesting that each subunit is mainly influenced by one of its
      neighbors. These observations are relevant for patients suffering from SPG4-type
      hereditary spastic paraplegia and explain why single amino acid exchanges lead to
      a dominant negative phenotype. In severing assays, wild type spastin is even more
      sensitive toward the presence of inactive mutants than in enzymatic assays,
      suggesting a weak coupling of ATPase and severing activity.

PMID- 22637578
TI  - Microtubule capture by mitotic kinesin centromere protein E (CENP-E).
AB  - Centromere protein E, CENP-E, is a kinetochore-associated kinesin-7 that
      establishes the microtubule-chromosome linkage and transports monooriented
      chromosomes to the spindle equator along kinetochore fibers of already bioriented
      chromosomes. As a processive kinesin, CENP-E uses a hand-over-hand mechanism, yet
      a number of studies suggest that CENP-E exhibits mechanistic differences from
      other processive kinesins that may be important for its role in chromosome
      congression. The results reported here show that association of CENP-E with the
      microtubule is unusually slow at 0.08 MUM(-1) s(-1) followed by slow ADP release
      at 0.9 s(-1). ATP binding and hydrolysis are fast with motor dissociation from
      the microtubule at 1.4 s(-1), suggesting that CENP-E head detachment from the
      microtubule, possibly controlled by phosphate release, determines the rate of
      stepping during a processive run because the rate of microtubule gliding
      corresponds to 1.4 steps/s. We hypothesize that the unusually slow CENP-E
      microtubule association step favors CENP-E binding of stable microtubules over
      dynamic ones, a mechanism that would bias CENP-E binding to kinetochore fibers.

PMID- 22637579
TI  - The TGFbeta receptor-interacting protein km23-1/DYNLRB1 plays an adaptor role in
      TGFbeta1 autoinduction via its association with Ras.
AB  - We have previously elucidated the signaling events that are required for TGFbeta1
      autoinduction (Yue, J., and Mulder, K. M. (2000) J. Biol. Chem. 275, 30765
      30773). Further, we have reported that the TGFbeta receptor (TbetaR)-interacting
      protein km23-1 plays an important role in TGFbeta signal transduction (Jin, Q.,
      Ding, W., and Mulder, K. M. (2007) J. Biol. Chem. 282, 19122-19132). Here we
      examined the role of km23-1 in TGFbeta1 autoinduction in TGFbeta-sensitive
      epithelial cells. siRNA blockade of km23-1 reduced TGFbeta1 mRNA expression, as
      well as DNA binding and transcriptional activation of the relevant activator
      protein-1 site in the human TGFbeta1 promoter. Further, knockdown of km23-1
      inhibited TGFbeta-mediated activation of ERK and JNK, phosphorylation of c-Jun,
      and transactivation of the c-Jun promoter. Sucrose gradient analyses indicate
      that km23-1 was present in lipid rafts together with Ras and TbetaRII after
      TGFbeta treatment. Immunoprecipitation/blot analyses revealed the formation of a
      TGFbeta-inducible complex between Ras and km23-1 in vivo within minutes of
      TGFbeta addition. Moreover, we demonstrate for the first time that km23-1 is
      required for Ras activation by TGFbeta. Our results indicate that km23-1 is
      required for TGFbeta1 autoinduction through Smad2-independent Ras/ERK/JNK
      pathways. More importantly, our findings demonstrate that km23-1 functions as a
      critical adaptor coupling TbetaR activation to activation of Ras effector
      pathways downstream.

PMID- 22637580
TI  - G146V mutation at the hinge region of actin reveals a myosin class-specific
      requirement of actin conformations for motility.
AB  - The G146V mutation in actin is dominant lethal in yeast. G146V actin filaments
      bind cofilin only minimally, presumably because cofilin binding requires the
      large and small actin domains to twist with respect to one another around the
      hinge region containing Gly-146, and the mutation inhibits that twisting motion.
      A number of studies have suggested that force generation by myosin also requires
      actin filaments to undergo conformational changes. This prompted us to examine
      the effects of the G146V mutation on myosin motility. When compared with wild
      type actin filaments, G146V filaments showed a 78% slower gliding velocity and a
      70% smaller stall force on surfaces coated with skeletal heavy meromyosin. In
      contrast, the G146V mutation had no effect on either gliding velocity or stall
      force on myosin V surfaces. Kinetic analyses of actin-myosin binding and ATPase
      activity indicated that the weaker affinity of actin filaments for myosin heads
      carrying ADP, as well as reduced actin-activated ATPase activity, are the cause
      of the diminished motility seen with skeletal myosin. Interestingly, the G146V
      mutation disrupted cooperative binding of myosin II heads to actin filaments.
      These data suggest that myosin-induced conformational changes in the actin
      filaments, presumably around the hinge region, are involved in mediating the
      motility of skeletal myosin but not myosin V and that the specific structural
      requirements for the actin subunits, and thus the mechanism of motility, differ
      among myosin classes.

PMID- 22637581
TI  - C-terminal fragment of N-cadherin accelerates synapse destabilization by amyloid
      beta.
AB  - The aetiology of Alzheimer's disease is thought to include functional impairment
      of synapses and synapse loss as crucial pathological events leading to cognitive
      dysfunction and memory loss. Oligomeric amyloid-beta peptides are well known to
      induce functional damage, destabilization and loss of brain synapses. However,
      the complex molecular mechanisms of amyloid-beta action resulting ultimately in
      synapse elimination are incompletely understood, thus limiting knowledge of
      potential therapeutic targets. Under physiological conditions, long-term synapse
      stability is mediated by trans-synaptically interacting adhesion molecules such
      as the homophilically binding N-cadherin/catenin complexes. In this study, we
      addressed whether inhibition of N-cadherin function affects amyloid-beta-induced
      synapse impairment. We found that blocking N-cadherin function, both by specific
      peptides interfering with homophilic binding and by expression of a dominant
      negative, ectodomain-deleted N-cadherin mutant, resulted in a strong acceleration
      of the effect of amyloid-beta on synapse function in cultured cortical neurons.
      The frequency of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)
      receptor-mediated miniature excitatory postsynaptic currents was reduced upon
      amyloid-beta application much earlier than observed in controls. We further
      hypothesized that ectodomain-shed, transmembrane C-terminal fragments that are
      generated during N-cadherin proteolytic processing might similarly enhance
      amyloid-beta-induced synapse damage. Indeed, expression of human N-cadherin C
      terminal fragment 1 strongly accelerated amyloid-beta-triggered synapse
      impairment. Ectodomain-shed N-cadherin C-terminal fragment 1 is further
      proteolytically cleaved by gamma-secretase. Therefore, both pharmacological
      inhibition of gamma-secretase and expression of the dominant-negative presenilin
      1 mutant L166P were used to increase the presence of endogeneous N-cadherin C
      terminal fragment 1. Under these conditions, we again found a strong acceleration
      of amyloid-beta-induced synapse impairment, which could be compensated by over
      expression of full-length N-cadherin. Intriguingly, western blot analysis of post
      mortem brains from patients with Alzheimer's disease revealed an enhanced
      presence of N-cadherin C-terminal fragment 1. Thus, an inhibition of N-cadherin
      function by proteolytically generated N-cadherin C-terminal fragment 1 might play
      an important role in Alzheimer's disease progression by accelerating amyloid-beta
      triggered synapse damage.

PMID- 22637640
TI  - High-resolution computed tomography findings of swine-origin influenza A (H1N1)
      virus (S-OIV) infection: comparison with scrub typhus.
AB  - BACKGROUND: Swine-origin influenza A (H1N1) virus (S-OIV) infection and scrub
      typhus, also known as tsutsugamushi disease can manifest as acute respiratory
      illnesses, particularly during the late fall or early winter, with similar
      radiographic findings, such as a predominance of ground-glass opacity (GGO).
      PURPOSE: To differentiate S-OIV infection from scrub typhus using high-resolution
      computed tomography (HRCT). MATERIAL AND METHODS: We retrospectively reviewed the
      HRCT findings of 14 patients with S-OIV infection and 10 patients with scrub
      typhus. We assessed the location, cross-sectional distribution, and the presence
      of a peribronchovascular distribution of GGO and consolidations on HRCT. We also
      assessed the presence of interlobular septal thickening, bronchial wall
      thickening, pneumothorax, pneumomediastinum, pleural effusion, and mediastinal or
      axillary lymph node enlargement. RESULTS: Scrub typhus was more common than S-OIV
      in elderly patients (P < 0.001). The monthly incidences of S-OIV and scrub typhus
      infection reached a peak between October and November. About 86% of S-OIV
      patients and 80% of scrub typhus patients presented with GGO. About 67% of the
      GGO lesions in S-OIV had a peribronchovascular distribution, but this was absent
      in scrub typhus (P = 0.005). Consolidation (93% vs. 10%, P < 0.001) and bronchial
      wall thickening (43% vs. 0%, P = 0.024) were more frequent in S-OIV infection
      than scrub typhus. Interlobular septal thickening (90% vs. 36%, P = 0.013) and
      axillary lymphadenopathy (90% vs. 0%, P < 0.001) were more common in scrub typhus
      than S-OIV infection. CONCLUSION: There was considerable overlap in HRCT findings
      between S-OIV infection and scrub typhus. However, S-OIV showed a distinctive
      peribronchovascular distribution of GGO lesions. Consolidation and bronchial wall
      thickening were seen more frequently in S-OIV infection, whereas interlobular
      septal thickening and axillary lymphadenopathy were more common in scrub typhus.
      Thus, CT could be helpful for differential diagnosis between S-OIV infection and
      scrub typhus.

PMID- 22637583
TI  - Apolipoprotein E4 effects in Alzheimer's disease are mediated by synaptotoxic
      oligomeric amyloid-beta.
AB  - The apolipoprotein E epsilon4 gene is the most important genetic risk factor for
      sporadic Alzheimer's disease, but the link between this gene and
      neurodegeneration remains unclear. Using array tomography, we analysed >50000
      synapses in brains of 11 patients with Alzheimer's disease and five non-demented
      control subjects and found that synapse loss around senile plaques in Alzheimer's
      disease correlates with the burden of oligomeric amyloid-beta in the neuropil and
      that this synaptotoxic oligomerized peptide is present at a subset of synapses.
      Further analysis reveals apolipoprotein E epsilon4 patients with Alzheimer's
      disease have significantly higher oligomeric amyloid-beta burden and exacerbated
      synapse loss around plaques compared with apolipoprotein E epsilon3 patients.
      Apolipoprotein E4 protein colocalizes with oligomeric amyloid-beta and enhances
      synaptic localization of oligomeric amyloid-beta by >5-fold. Biochemical
      characterization shows that the amyloid-beta enriched at synapses by
      apolipoprotein E4 includes sodium dodecyl sulphate-stable dimers and trimers. In
      mouse primary neuronal culture, lipidated apolipoprotein E4 enhances oligomeric
      amyloid-beta association with synapses via a mechanism involving apolipoprotein E
      receptors. Together, these data suggest that apolipoprotein E4 is a co-factor
      that enhances the toxicity of oligomeric amyloid-beta both by increasing its
      levels and directing it to synapses, providing a link between apolipoprotein E
      epsilon4 genotype and synapse loss, a major correlate of cognitive decline in
      Alzheimer's disease.

PMID- 22637582
TI  - Social cognitive deficits and their neural correlates in progressive supranuclear
      palsy.
AB  - Although progressive supranuclear palsy is defined by its akinetic rigidity,
      vertical supranuclear gaze palsy and falls, cognitive impairments are an
      important determinant of patients' and carers' quality of life. Here, we
      investigate whether there is a broad deficit of modality-independent social
      cognition in progressive supranuclear palsy and explore the neural correlates for
      these. We recruited 23 patients with progressive supranuclear palsy (using
      clinical diagnostic criteria, nine with subsequent pathological confirmation) and
      22 age- and education-matched controls. Participants performed an auditory
      (voice) emotion recognition test, and a visual and auditory theory of mind test.
      Twenty-two patients and 20 controls underwent structural magnetic resonance
      imaging to analyse neural correlates of social cognition deficits using voxel
      based morphometry. Patients were impaired on the voice emotion recognition and
      theory of mind tests but not auditory and visual control conditions. Grey matter
      atrophy in patients correlated with both voice emotion recognition and theory of
      mind deficits in the right inferior frontal gyrus, a region associated with
      prosodic auditory emotion recognition. Theory of mind deficits also correlated
      with atrophy of the anterior rostral medial frontal cortex, a region associated
      with theory of mind in health. We conclude that patients with progressive
      supranuclear palsy have a multimodal deficit in social cognition. This deficit is
      due, in part, to progressive atrophy in a network of frontal cortical regions
      linked to the integration of socially relevant stimuli and interpretation of
      their social meaning. This impairment of social cognition is important to
      consider for those managing and caring for patients with progressive supranuclear
      palsy.

PMID- 22637641
TI  - Bladder cancer: utility of MRI in detection of occult muscle-invasive disease.
AB  - BACKGROUND: The presence of muscularis propria invasion by bladder cancer is a
      key factor in prognosis and treatment decisions, although may be missed by biopsy
      due to sampling error. MRI has shown potential for detection of muscle invasion
      but has not specifically been evaluated for this purpose in the setting of
      bladder cancer patients without evidence of muscle invasion on initial biopsy.
      PURPOSE: To evaluate the role of MRI in detection of muscularis propria invasion
      by bladder cancer following a pathologic diagnosis of non-invasive tumor.
      MATERIAL AND METHODS: This retrospective study included 23 patients who underwent
      pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis
      propria invasion and in whom additional histologic evaluation was performed
      following MRI. Two radiologists in consensus reviewed T2-weighted images to
      identify those cases suspicious for muscle invasion on MRI. The radiologists
      identified whether cases suspicious for invasion demonstrated disruption of the
      T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding,
      and peri-vesical soft tissue nodularity. Findings were compared with pathologic
      results obtained after MRI. RESULTS: Suspicion was raised for muscle invasion in
      eight of 23 cases, four of which exhibited invasion on follow-up pathology. No
      case without suspicion on MRI exhibited invasion on follow-up pathology.
      Therefore, sensitivity and specificity were 100% and 79%, respectively. Among
      individual findings, muscularis disruption on T2WI exhibited sensitivity of 100%
      and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and
      specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited
      sensitivity and specificity of 25% and 100%. CONCLUSION: MRI demonstrated high
      sensitivity for detection of muscle invasion in cases of bladder cancer without
      invasion on initial histologic assessment. Muscularis disruption on T2WI appeared
      to exhibit a better combination of sensitivity and specificity than did peri
      vesical changes.

PMID- 22637642
TI  - Prevalence of extravertebral cement leakage after vertebroplasty: procedural
      documentation versus CT detection.
AB  - BACKGROUND: Reported incidence of extravertebral cement leakage after
      vertebroplasty varies widely across studies. PURPOSE: To retrospectively compare
      the relative detection rates of extravertebral leakage noted under intra
      procedural fluoroscopic surveillance, postprocedure plain radiographs, and
      postprocedure computed tomography (CT) in a cohort of patients undergoing
      vertebroplasty. MATERIAL AND METHODS: With IRB approval, we retrospectively
      identified 181 patients with 277 levels treated with percutaneous vertebroplasty
      among a total of 1255 patients undergoing vertebroplasty between 1999 and 2010
      who had subsequently undergone a CT examination that included the treated
      level(s). Categories of leakage were paravertebral, end plate, epidural, and
      prevertebral venous leakage. CT-detected leak rates were then compared to those
      noted on the vertebroplasty procedure reports and the archived fluoroscopic
      images for this same cohort using Pearson's chi(2) test. RESULTS: One hundred and
      forty-nine (82%, 95% CI 76-87%) of 181 patients demonstrated evidence of some
      type of leakage on CT at one or more treated levels. Sixty-two (34%, 95% CI 28
      42%) and seventy-seven (50%, 95% CI 43-57%) of 149 CT-detected leaks were
      reported in the procedural dictation or detected on plain radiography (P = 0.01
      and 0.006, respectively). The most common type of leakage noted on CT was end
      plate (n = 81, 45%, 95% CI 38-52%), followed by paravertebral (n = 64, 35%, 95%
      CI 29-43%), epidural (n = 36, 20%, 95% CI 15-26%), and prevertebral venous (n =
      32, 18%, 95% CI 13-24%). CONCLUSION: Cement leakage after vertebroplasty is
      common and is often not reported by operators in procedural dictations. CT
      detects substantially more leaks than plain radiography.

PMID- 22637643
TI  - Integrin-linked kinase at a glance.

PMID- 22637644
TI  - The non-coding 3' UTR of CD44 induces metastasis by regulating extracellular
      matrix functions.
AB  - The importance of non-coding RNA transcripts in regulating microRNA (miRNA)
      functions, especially the 3'-untranslated region (3' UTR), has been revealed in
      recent years. Genes encoding the extracellular matrix normally produce large mRNA
      transcripts including the 3' UTR. How these large transcripts affect miRNA
      functions and how miRNAs modulate extracellular matrix protein expression are
      largely unknown. Here, we demonstrate that the overexpression of the CD44 3' UTR
      results in enhanced cell motility, invasion and cell adhesion in human breast
      carcinoma cell line MDA-MB-231. Furthermore, we found that expression of the CD44
      3' UTR enhances metastasis in vivo. We hypothesize that increased expression of
      the CD44 3' UTR affects miRNA binding and modulates synthesis of the
      extracellular matrix. Computational analysis indicated that miRNAs that interact
      with the CD44 3' UTR also have binding sites in other matrix-encoding mRNA 3'
      UTRs, including collagen type 1alpha1 (Col1alpha1) repressed by miR-328 and
      fibronectin type 1 (FN1) repressed by miR-512-3p, miR-491 and miR-671. Protein
      analysis demonstrated that expression of CD44, Col1alpha1 and FN1 were
      synergistically upregulated in vitro and in vivo upon transfection of the CD44 3'
      UTR. The non-coding 3' UTR of CD44 interacts with multiple miRNAs that target
      extracellular matrix properties and thus can be used to antagonize miRNA
      activities.

PMID- 22637653
TI  - Inexpensive, realtime tele-ultrasound using a commercial, web-based video
      streaming device.
AB  - We have devised an inexpensive, web-based tele-ultrasound system using
      commercially-available video streaming equipment. We examined the spatial and
      grey scale resolution, and the delay time of the system. The receiving PC was
      tested at various distances from the transmitting site, from 3.2 km to 4828 km.
      Standard resolution targets and echocardiography movie strips recorded on DVDs
      were used to assess the image quality. A qualitative assessment was made by an
      expert sonographer. As the distance between the transmitter and the receiver
      increased, the scan smoothness decreased and the delay increased. At a distance
      of 3.2 km the delay was 2-3 s, and at 4828 km it was 10-15 s. The delay was short
      enough to allow realtime guidance of the scanning technician by telephone. The
      system allows inexpensive, readily available, realtime tele-ultrasonography.

PMID- 22637694
TI  - Hexane fraction of American ginseng suppresses colitis and colon cancer.

PMID- 22637695
TI  - Acute kidney injury in decompensated cirrhosis.
AB  - BACKGROUND: Hepatorenal syndrome in cirrhosis with ascites is a well-defined
      entity with significant morbidity and mortality. It is unclear whether milder
      degrees of acute kidney injury (AKI), defined as a serum creatinine increase of
      over 26.4 MUmol/l (0.3 mg/dl) or by 50% from baseline, also has a negative impact
      on patient outcomes. OBJECTIVES: To determine the prevalence of AKI in cirrhosis
      with ascites and the impact of AKI on patient outcomes. DESIGN: Patients with
      cirrhosis with ascites and baseline serum creatinine less than 110 MUmol/l, and
      no evidence of structural renal disease, prospectively underwent 4-6-weekly blood
      work-up for full blood count, biochemistry and liver function. Clinical
      assessments occurred every 4 months for the development of AKI and other
      complications. RESULTS: 90 patients (mean age 55.8 +/- 0.8 years) with a mean
      follow-up of 14.05 +/- 1.07 months were enrolled. 82 episodes of AKI occurred in
      49 patients, with the majority of episodes precipitated by a disturbance in
      systemic haemodynamics. The mean peak serum creatinine of the AKI episodes was
      within the laboratory's normal range. 73 episodes of AKI resolved; nine did not.
      There was no clear clinical predictor for the development or resolution of AKI.
      Despite resolution of most AKI episodes, a gradual and significant increase in
      serum creatinine and a gradual reduction in mean arterial pressure were observed
      during follow-up, associated with a significant reduction in survival compared
      with non-AKI patients. CONCLUSION: Minor increases in serum creatinine are
      clinically relevant and can adversely affect survival. Every effort should be
      made to avoid precipitation of AKI in cirrhosis and ascites.

PMID- 22637696
TI  - In situ validation of an intestinal stem cell signature in colorectal cancer.
AB  - OBJECTIVE: Wnt/Tcf, Lgr5, Ascl2 and/or Bmi1 signalling is believed to define the
      mouse intestinal stem cell niche(s) from which adenomas arise. The aim of this
      study was to determine the relevance of these putative intestinal stem cell
      markers to human colorectal cancer. DESIGN: 19 putative intestinal stem cell
      markers, including Ascl2 and Lgr5, were identified from published data and an
      evaluation of a human colorectal gene expression database. Associations between
      these genes were assessed by isotopic in situ hybridisation (ISH) in 57
      colorectal adenocarcinomas. Multiplex fluorescent ISH and chromogenic non
      isotopic ISH were performed to confirm expression patterns. The prognostic
      significance of Lgr5 was assessed in 891 colorectal adenocarcinomas. RESULTS:
      Ascl2 and Lgr5 were expressed in 85% and 74% of cancers respectively, and
      expression was positively correlated (p=0.003). Expression of Bmi1 was observed
      in 47% of cancers but was very weak in 98% of cases with expression. Both Ascl2
      and/or Lgr5 were positively correlated with the majority of genes in the
      signature but neither was correlated with Cdk6, Gpx2, Olfm4 or Tnfrsf19. Lgr5 did
      not have prognostic significance. CONCLUSION: These data suggest that 74-85% of
      colorectal cancers express a Lgr5/Ascl2 associated signature and support the
      hypothesis that they derive from Lgr5(+)/Ascl2(+) crypt stem cells, not Bmi1(+)
      stem cells. However, Olfm4 was not found to be a useful marker of Lgr5(+) cells
      in normal colon or tumours. In this large series, Lgr5 expression is not
      associated with increased tumour aggressiveness, as might be expected from a
      cancer stem cell marker.

PMID- 22637697
TI  - Ischaemia-induced mucus barrier loss and bacterial penetration are rapidly
      counteracted by increased goblet cell secretory activity in human and rat colon.
AB  - OBJECTIVE: Colonic ischaemia is frequently observed in clinical practice. This
      study provides a novel insight into the pathophysiology of colon
      ischaemia/reperfusion (IR) using a newly developed human and rat experimental
      model. DESIGN: In 10 patients a small part of colon that had to be removed for
      surgical reasons was isolated and exposed to 60 min of ischaemia (60I)
      with/without different periods of reperfusion (30R and 60R). Tissue not exposed
      to IR served as control. In rats, colon was exposed to 60I, 60I/30R, 60I/120R or
      60I/240R (n=7 per group). The tissue was snap-frozen or fixed in glutaraldehyde,
      formalin or methacarn fixative. Mucins were stained with Periodic Acid
      Schiff/Alcian Blue (PAS/AB) and MUC2/Dolichos biflorus agglutinin (DBA). Bacteria
      were studied using electron microscopy (EM) and fluorescent in situ hybridisation
      (FISH). Neutrophils were studied using myeloperoxidase staining. qPCR was
      performed for MUC2, interleukin (IL)-6, IL-1beta and tumour necrosis factor
      alpha. RESULTS: In rats, PAS/AB and MUC2/DBA staining revealed mucus layer
      detachment at ischaemia which was accompanied by bacterial penetration (in EM and
      FISH). Human and rat studies showed that, simultaneously, goblet cell secretory
      activity increased. This was associated with expulsion of bacteria from the
      crypts and restoration of the mucus layer at 240 min of reperfusion. Inflammation
      was limited to minor influx of neutrophils and increased expression of
      proinflammatory cytokines during reperfusion. CONCLUSIONS: Colonic ischaemia
      leads to disruption of the mucus layer facilitating bacterial penetration. This
      is rapidly counteracted by increased secretory activity of goblet cells, leading
      to expulsion of bacteria from the crypts as well as restoration of the mucus
      barrier.

PMID- 22637698
TI  - Expression of B and T lymphocyte attenuator (BTLA) in macrophages contributes to
      the fulminant hepatitis caused by murine hepatitis virus strain-3.
AB  - OBJECTIVES: Fulminant viral hepatitis (FH) remains a serious clinical problem for
      which the underlying pathogenesis remains unclear. The B and T lymphocyte
      attenuator (BTLA) is an immunoglobulin-domain-containing protein that has the
      capacity to maintain peripheral tolerance and limit immunopathological damage
      during immune responses. However, its precise role in FH has yet to be
      investigated. DESIGN: BTLA-deficient (BTLA-/-) mice and their wild-type
      littermates were infected with murine hepatitis virus strain-3 (MHV-3), and the
      levels of tissue damage, cell apoptosis, serum liver enzymes, fibrinogen-like
      protein 2 (FGL2) and cytokine production were measured and compared. Survival
      rate was studied after MHV-3 infection with or without adoptive transferring
      macrophages. RESULTS: FGL2 production, liver and spleen damage, and mortality
      were significantly reduced in BTLA-/- mice infected with MHV-3. This effect is
      due to rapid, TRAIL (TNF-related apoptosis-inducing ligand)-dependent apoptosis
      of MHV-3-infected macrophages in BTLA-/- mice. The early loss of macrophages
      resulted in reduced pathogenic tumour necrosis factor alpha (TNFalpha) and FGL2
      levels and lower viral titres. The importance of TNFalpha in MHV-3-induced
      pathology was demonstrated by increased mortality in TNFalpha-treated MHV-3
      infected BTLA-/- mice, whereas TNFalpha-/- mice were resistant to the infection.
      Moreover, adoptively transferring macrophages to BTLA-/- mice caused
      sensitisation, whereas blocking BTLA protected wild-type mice from virus-induced
      FH mortality. CONCLUSIONS: BTLA promotes the pathogenesis of virus-induced FH by
      enhancing macrophage viability and function. Targeting BTLA may be a novel
      strategy for the treatment of FH.

PMID- 22637700
TI  - Microbes and metabolic health.

PMID- 22637699
TI  - Novel roles of liver sinusoidal endothelial cell lectin in colon carcinoma cell
      adhesion, migration and in-vivo metastasis to the liver.
AB  - OBJECTIVE: Adhesion molecules play an important role in tumour metastasis. The
      liver is a frequent target for the metastasis of several tumour types. However,
      virtually no liver-specific adhesion molecules have been described in terms of
      organ-specific metastasis. This study aimed to determine the role of liver
      sinusoidal endothelial cell lectin (LSECtin) in colon carcinoma metastasis to the
      liver. DESIGN: The role of LSECtin in colon carcinoma metastasis to the liver was
      determined by LSECtin knockout nude mice and anti-LSECtin antibody. LSECtin
      promoting the migration of LS174T and LoVo cells was determined by transwell
      experiment. The serum levels of soluble LSECtin in patients were elevated by
      ELISA. RESULTS: LSECtin was found to adhere to LS174T and LoVo colon cancer cells
      in vitro and in vivo. Deficiency or blocking of LSECtin significantly decreased
      hepatic metastases of LS174T and LoVo cells. Primary colon cancer cells from
      patients also exhibited remarkably low rates of hepatic metastasis in LSECtin
      knockout mice. LSECtin promoted the migration of LS174T and LoVo cells and
      increased the expression of c-Met in these cells. Serum soluble LSECtin was
      detected at significantly higher levels in colon cancer patients with or without
      hepatic metastases compared with healthy controls and was also increased in colon
      cancer patients with metastases compared with those without metastases.
      CONCLUSION: The results indicate that LSECtin plays an important role in
      colorectal carcinoma liver metastasis and may be a promising new target for
      intervention in metastasis formation.

PMID- 22637701
TI  - Adipose-derived mesenchymal stromal cells induce immunomodulatory macrophages
      which protect from experimental colitis and sepsis.
AB  - OBJECTIVE: To investigate the effect of adipose-derived mesenchymal stromal cells
      (ASCs) on the activation state of macrophages (MPhi) in vitro, and the potential
      therapeutic effect of these cells in experimental colitis and sepsis. DESIGN:
      Murine bone marrow-derived macrophages were cultured with ASCs or with ASC
      conditioned media (ASC-MPhi) and characterised for the expression of several
      regulatory macrophage markers, including enzymes and cytokines, and for their
      immunomodulatory capacity in vitro. The therapeutic effect was investigated of
      ASC-MPhi in two models of experimental inflammatory colitis induced by
      trinitrobenzene sulphonic acid and dextran sodium sulphate, and in polymicrobial
      sepsis induced by caecal ligation and puncture. RESULTS: ASC-MPhi showed a
      phenotype that clearly differed from the classically activated macrophages or the
      alternatively activated macrophages induced by interleukin (IL)-4, characterised
      by high arginase activity, increased production of IL-10 upon restimulation and
      potent immunosuppressive activity on T cells and macrophages. Activation of cyclo
      oxygenase-2 on ASCs seems to be critically involved in inducing this phenotype.
      Systemic infusion of ASC-MPhi inhibited colitis in mice, reducing mortality and
      weight loss while lowering the colonic and systemic levels of inflammatory
      cytokines. Importantly, therapeutic injection of ASC-MPhi in established chronic
      colitis alleviated its progression and avoided disease recurrence. Moreover, ASC
      MPhi protected from severe sepsis by reducing the infiltration of inflammatory
      cells into various organs and by downregulating the production of several
      inflammatory mediators, where ASC-MPhi-derived IL-10 played a critical role.
      CONCLUSION: ASCs induce a distinct regulatory activation state of macrophages
      which possess potent immunomodulatory ability and therapeutic potential in
      inflammatory bowel diseases and sepsis.

PMID- 22637702
TI  - Diarrhoea-predominant irritable bowel syndrome: an organic disorder with
      structural abnormalities in the jejunal epithelial barrier.
AB  - OBJECTIVE: Recently, the authors demonstrated altered gene expression in the
      jejunal mucosa of diarrhoea-predominant irritable bowel syndrome patients (IBS
      D); specifically, the authors showed that genes related to mast cells and the
      intercellular apical junction complex (AJC) were expressed differently than in
      healthy subjects. The aim of the authors here was to determine whether these
      alterations are associated with structural abnormalities in AJC and their
      relationship with mast cell activation and IBS-D clinical manifestations. DESIGN:
      A clinical assessment and a jejunal biopsy were obtained in IBS-D patients (n=45)
      and healthy subjects (n=30). Mucosal mast cell number and activation were
      determined by quantifying CD117(+) cells/hpf and tryptase expression,
      respectively. Expression and distribution of AJC specific proteins were evaluated
      by western blot and confocal microscopy. AJC ultrastructure was assessed by
      transmission electron microscopy. RESULTS: Compared with healthy subjects, IBS-D
      patients exhibited: (a) increased mast cell counts and activation; (b) increased
      protein expression of claudin-2, reduced occludin phosphorylation and enhanced
      redistribution from the membrane to the cytoplasm; and (c) increased myosin
      kinase expression, reduced myosin phosphatase and, consequently, enhanced
      phosphorylation of myosin. These molecular alterations were associated with
      ultrastructural abnormalities at the AJC, specifically, perijunctional
      cytoskeleton condensation and enlarged apical intercellular distance. Moreover,
      AJC structural alterations positively correlated both with mast cell activation
      and clinical symptoms. CONCLUSION: The jejunal mucosa of IBS-D patients displays
      disrupted apical junctional complex integrity associated with mast cell
      activation and clinical manifestations. These results provide evidence for the
      organic nature of IBS-D, a heretofore model disease of functional
      gastrointestinal disorders.

PMID- 22637704
TI  - Caregiving for older Latinos at end of life: perspectives from paid and family
      (unpaid) caregivers.
AB  - This study examined the various settings in which caregiving occurred for
      terminally ill older Latinos. Qualitative data were collected in Central Florida
      through in-depth, semi-structured, open-ended interviews. 20 Latinos caring for
      terminally ill Latinos participated in the study. N = 9 Latino family (unpaid)
      caregivers provided care in the terminally ill person's home, while N = 4
      provided care to a family member in the caregiver's home. N = 4 paid caregivers
      provided care to terminally ill Latinos who reside in the caregiver's private
      home and N = 3 in an assisted-living facility. The themes indicate that family
      (unpaid) caregivers experienced changes in their financial status; they both
      encountered English language barriers. Geographical distance made caregiving more
      challenging. Paid caregivers adapted to cultural expectations and their higher
      income enabled them to hire assistance.

PMID- 22637703
TI  - Transcriptome analysis identifies TNF superfamily receptors as potential
      therapeutic targets in alcoholic hepatitis.
AB  - OBJECTIVE: Alcoholic hepatitis (AH) is a severe clinical condition that needs
      novel therapies. The identification of targets for therapy is hampered by the
      lack of animal models of advanced AH. The authors performed a translational study
      through a transcriptome analysis in patients with AH to identify new molecular
      targets. DESIGN: Hepatic gene expression profiling was assessed by DNA microarray
      in patients with AH (n=15) and normal livers (n=7). Functional analysis was
      assessed by gene set enrichment analysis. Quantitative PCR was performed in
      patients with AH (n=40), hepatitis C (n=18), non-alcoholic steatohepatitis (n=20)
      and in mouse models of acute and chronic liver injury. Protein expression was
      assessed by immunohistochemistry and western blotting. RESULTS: Gene expression
      analysis showed 207 genes >5-fold differentially expressed in patients with AH
      and revealed seven pathways differentially regulated including 'cytokine-cytokine
      receptor interaction'. Several tumour necrosis factor (TNF) superfamily
      receptors, but not ligands, were overexpressed in AH. Importantly, Fn14 was the
      only TNF superfamily receptor exclusively upregulated in AH compared with other
      liver diseases and correlated with both 90-day mortality and severity of portal
      hypertension. Fn14 protein expression was detected in areas of fibrogenesis and
      in a population of hepatocytes. Fn14 expression was increased in experimental
      models of liver injury and was detected in progenitor cells. CONCLUSION:
      Translational research revealed that TNF superfamily receptors are overexpressed
      in AH. Fn14, the receptor for TNF-like weak inducer of apoptosis, is selectively
      upregulated in patients with AH. TNF superfamily receptors could represent a
      potential target for therapy.

PMID- 22637705
TI  - Home versus hospital mortality from cancer in Mexico (1999-2009).
AB  - OBJECTIVE: To analyze the place of death from cancer in Mexico from 1999 to 2009
      and find the associated factors. METHODS: We collected data on mortality by
      cancer from the national database including age, gender, area of residence, level
      of education, place of death, and type of cancer. RESULTS: The proportion of
      deaths at home and hospital was 55.67% and 39%, respectively. Factors associated
      with home deaths were old age, female gender, rural area of residence, and lack
      of formal education. There was a short but significant decrease in home deaths
      for cervical cancer and leukemia. CONCLUSIONS: In Mexico, mortality in home is
      greater than in hospital for patients with cancer. Our results have important
      implications for palliative care professionals and health services of Mexico.

PMID- 22637706
TI  - Individual differences in subjective experience and objective performance in
      metacontrast masking.
AB  - When participants discriminate stimuli that are masked by a following stimulus
      via metacontrast masking, stable individually different masking functions have
      been found despite identical stimulation conditions.In the present study, in one
      group of observers objective performance increased with increasing target-mask
      stimulus onset asynchrony (SOA), whereas in another group performance decreased
      with increasing SOA. In addition, a group of overachievers showed ceiling effects
      whereas a group of underachievers hardly exceeded chance levels of performance
      irrespective of SOA. The differences between observers' objective measures of
      performance correspond to differences in participants' phenomenological reports
      of subjective experience. This indicates that participants differ in their access
      to specific perceptual cues that they use spontaneously to solve the task. When
      we instructed participants to use only one specific cue, the instructed cue
      determined participants' objective performance considerably in two experiments.
      Nevertheless, masking functions remained similar with and without the cued
      instruction, and the effect of cues depended on the initial masking function of
      individuals. Findings suggest that individuals with different masking functions
      differ also in terms of phenomenology, used cues, and response strategy. The
      relation between subjective experience, reported usage of perceptual cues, and
      objective performance in the metacontrast masking task deserves further
      investigation.

PMID- 22637707
TI  - Accurate planning of manual tracking requires a 3D visuomotor transformation of
      velocity signals.
AB  - Humans often perform visually guided arm movements in a dynamic environment. To
      accurately plan visually guided manual tracking movements, the brain should
      ideally transform the retinal velocity input into a spatially appropriate motor
      plan, taking the three-dimensional (3D) eye-head-shoulder geometry into account.
      Indeed, retinal and spatial target velocity vectors generally do not align
      because of different eye-head postures. Alternatively, the planning could be
      crude (based only on retinal information) and the movement corrected online using
      visual feedback. This study aims to investigate how accurate the motor plan
      generated by the central nervous system is. We computed predictions about the
      movement plan if the eye and head position are taken into account (spatial
      hypothesis) or not (retinal hypothesis). For the motor plan to be accurate, the
      brain should compensate for the head roll and resulting ocular counterroll as
      well as the misalignment between retinal and spatial coordinates when the eyes
      lie in oblique gaze positions. Predictions were tested on human subjects who
      manually tracked moving targets in darkness and were compared to the initial arm
      direction, reflecting the motor plan. Subjects spatially accurately tracked the
      target, although imperfectly. Therefore, the brain takes the 3D eye-head-shoulder
      geometry into account for the planning of visually guided manual tracking.

PMID- 22637708
TI  - Of toothy grins and angry snarls--open mouth displays contribute to efficiency
      gains in search for emotional faces.
AB  - The emotional face-in-a-crowd effect is widely cited, but its origin remains
      controversial, particularly with photorealistic stimuli.     Recently, it has
      been suggested that one factor underlying the guidance of attention by a
      photorealistic emotional face in visual search might be the visibility of teeth,
      a hypothesis, however, that has not been studied systematically to date. The
      present experiments     manipulate the visibility of teeth experimentally and
      orthogonally to facial emotion. Results suggest that much of the face-in-a-crowd
      effect with photorealistic emotional faces is due to visible teeth, and that the
      visibility of teeth can create a search advantage for either a happy or an angry
      target face when teeth visibility and facial emotion are confounded. Further
      analyses clarify that the teeth visibility primarily affects the speed with which
      neutral crowds are scanned, shedding new light on the mechanism that evokes
      differences in search efficiency for different emotional expressions.

PMID- 22637709
TI  - The perceptual basis of common photographic practice.
AB  - Photographers, cinematographers, and computer-graphics engineers use certain
      techniques to create striking pictorial effects. By using lenses of different
      focal lengths, they can make a scene look compressed or expanded in depth, make a
      familiar object look natural or distorted, or make a person look smarter, more
      attractive, or more neurotic. We asked why pictures taken with a certain focal
      length look natural, while those taken with other focal lengths look distorted.
      We found that people's preferred viewing distance when looking at pictures leads
      them to view long-focal-length pictures from too near and short-focal-length
      pictures from too far. Perceptual distortions occur because people do not take
      their incorrect viewing distances into account. By following the rule of thumb of
      using a 50-mm lens, photographers greatly increase the odds of a viewer looking
      at a photograph from the correct distance, where the percept will be undistorted.
      Our theory leads to new guidelines for creating pictorial effects that are more
      effective than conventional guidelines.

PMID- 22637710
TI  - Anatomical constraints on attention: hemifield independence is a signature of
      multifocal spatial selection.
AB  - Previous studies have shown independent attentional selection of targets in the
      left and right visual hemifields during attentional tracking (Alvarez & Cavanagh,
      2005) but not during a visual search (Luck, Hillyard, Mangun, & Gazzaniga, 1989).
      Here we tested whether multifocal spatial attention is the critical process that
      operates independently in the two hemifields. It is explicitly required in
      tracking (attend to a subset of object locations, suppress the others) but not in
      the standard visual search task (where all items are potential targets). We used
      a modified visual search task in which observers searched for a target within a
      subset of display items, where the subset was selected based on location
      (Experiments 1 and 3A) or based on a salient feature difference (Experiments 2
      and 3B). The results show hemifield independence in this subset visual search
      task with location-based selection but not with feature-based selection; this
      effect cannot be explained by general difficulty (Experiment 4). Combined, these
      findings suggest that hemifield independence is a signature of multifocal spatial
      attention and highlight the need for cognitive and neural theories of attention
      to account for anatomical constraints on selection mechanisms.

PMID- 22637721
TI  - Testimony ceremonies in Asia: integrating spirituality in testimonial therapy for
      torture survivors in India, Sri Lanka, Cambodia, and the Philippines.
AB  - This study explores the therapeutic implications of including culturally adapted
      spiritual ceremonies in the process of testimonial therapy for torture survivors
      in India, Sri Lanka, Cambodia, and the Philippines. Data were collected through
      an action research process with Asian mental health and human rights
      organizations, during which the testimonial method was reconceptualized and
      modified to include four sessions. In the first two sessions, community workers
      assist survivors in the writing of their testimony, which is their narrative
      about the human rights violations they have suffered. In the third session,
      survivors participate in an honour ceremony in which they are presented with
      their testimony documents. In the fourth session, the community workers meet with
      the survivors for a reevaluation of their well-being. The honour ceremonies
      developed during the action research process came to employ different kinds of
      symbolic language at each site: human rights (India), religious/Catholic (Sri
      Lanka), religious/Buddhist (Cambodia), and religious/Moslem (Philippines). They
      all used embodied spirituality in various forms, incorporating singing, dancing,
      and religious purification rituals in a collective gathering. We suggest that
      these types of ceremonies may facilitate an individual's capacity to contain and
      integrate traumatic memories, promote restorative self-awareness, and engage
      community support. Additional research is needed to determine the method's
      applicability in other sociopolitical contexts governed by more Western-oriented
      medical traditions.

PMID- 22637722
TI  - The validation of a new comprehensive headache-specific quality of life
      questionnaire.
AB  - BACKGROUND: Measuring quality of life (QOL) is an important means of assessing
      the impact of headache. The currently used QOL questionnaires are usually geared
      toward migraine and focus on a limited number of factors, thus they are not
      necessarily informative in other headache types. We report the psychometric
      properties of a new questionnaire, the Comprehensive Headache-related Quality of
      life Questionnaire (CHQQ) that may be more sensitive to the burden of headache.
      PATIENTS AND METHODS: A total of 202 patients suffering from migraine (n = 168)
      or tension-type headache (TTH) (n = 34) completed the CHQQ and SF-36, a generic
      QOL questionnaire. We assessed the reliability and validity of the CHQQ and its
      physical, mental and social dimensions. RESULTS: The questionnaire was easy to
      administer. Reliability was excellent with Cronbach's alpha being 0.913 for the
      whole instrument (0.814-0.832 for its dimensions). The dimensions and total score
      showed significant correlations with the patients' headache characteristics
      (criterion validity), and were also significantly correlated with the SF-36
      domains (convergent validity). The total score and dimensions were significantly
      (p < 0.005) lower in the migraine group than in the TTH group (discriminative
      validity). CONCLUSION: In this study the new headache-specific QOL instrument
      showed adequate psychometric properties.

PMID- 22637723
TI  - Nodakenin suppresses lipopolysaccharide-induced inflammatory responses in
      macrophage cells by inhibiting tumor necrosis factor receptor-associated factor 6
      and nuclear factor-kappaB pathways and protects mice from lethal endotoxin shock.
AB  - Nodakenin, a coumarin isolated from the roots of Angelicae gigas, has been
      reported to possess neuroprotective, antiaggregatory, antibacterial, and memory
      enhancing effects. In the present study, we investigated the anti-inflammatory
      effects of nodakenin by examining its in vitro inhibitory effects on inducible
      nitric-oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory
      cytokines in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and mouse
      peritoneal macrophages and its in vivo effects on LPS-induced septic shock in
      mice. Our results indicate that nodakenin concentration-dependently inhibits iNOS
      and COX-2 at the protein, mRNA, and promoter binding levels, and these
      inhibitions cause attendant decreases in the production of nitric oxide (NO) and
      prostaglandin E2 (PGE2). Furthermore, we found that nodakenin inhibits the
      production and mRNA expression of tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-6, and IL-1beta induced by LPS. Molecular data revealed that
      nodakenin suppressed the transcriptional activity and translocation of nuclear
      factor-kappaB (NF-kappaB) by inhibiting inhibitory kappaB-alpha degradation and
      IkappaB kinase-alpha/beta phosphorylation. In addition, nodakenin was found to
      significantly inhibit the LPS-induced binding of transforming growth factor-beta
      activated kinase 1 to tumor necrosis factor receptor-associated factor 6 (TRAF6)
      by reducing TRAF6 ubiquitination. Pretreatment with nodakenin reduced the serum
      levels of NO, PGE2, and proinflammatory cytokines and increased the survival rate
      of mice with LPS-induced endotoxemia. Taken together, our data suggest that
      nodakenin down-regulates the expression of the proinflammatory iNOS, COX-2, TNF
      alpha, IL-6, and IL-1beta genes in macrophages by interfering with the activation
      of TRAF6, thus preventing NF-kappaB activation.

PMID- 22637724
TI  - Durable pharmacological responses from the peptide ShK-186, a specific Kv1.3
      channel inhibitor that suppresses T cell mediators of autoimmune disease.
AB  - The Kv1.3 channel is a recognized target for pharmaceutical development to treat
      autoimmune diseases and organ rejection. ShK-186, a specific peptide inhibitor of
      Kv1.3, has shown promise in animal models of multiple sclerosis and rheumatoid
      arthritis. Here, we describe the pharmacokinetic-pharmacodynamic relationship for
      ShK-186 in rats and monkeys. The pharmacokinetic profile of ShK-186 was evaluated
      with a validated high-performance liquid chromatography-tandem mass spectrometry
      method to measure the peptide's concentration in plasma. These results were
      compared with single-photon emission computed tomography/computed tomography data
      collected with an 111In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
      conjugate of ShK-186 to assess whole-blood pharmacokinetic parameters as well as
      the peptide's absorption, distribution, and excretion. Analysis of these data
      support a model wherein ShK-186 is absorbed slowly from the injection site,
      resulting in blood concentrations above the Kv1.3 channel-blocking IC50 value for
      up to 7 days in monkeys. Pharmacodynamic studies on human peripheral blood
      mononuclear cells showed that brief exposure to ShK-186 resulted in sustained
      suppression of cytokine responses and may contribute to prolonged drug effects.
      In delayed-type hypersensitivity, chronic relapsing-remitting experimental
      autoimmune encephalomyelitis, and pristane-induced arthritis rat models, a single
      dose of ShK-186 every 2 to 5 days was as effective as daily administration. ShK
      186's slow distribution from the injection site and its long residence time on
      the Kv1.3 channel contribute to the prolonged therapeutic effect of ShK-186 in
      animal models of autoimmune disease.

PMID- 22637725
TI  - Wnt/Snail signaling regulates cytochrome C oxidase and glucose metabolism.
AB  - Wnt signaling plays a critical role in embryonic development, and its
      deregulation is closely linked to the occurrence of a number of malignant tumors,
      including breast and colon cancer. The pathway also induces Snail-dependent
      epithelial-to-mesenchymal transition (EMT), which is responsible for tumor
      invasion and metastasis. In this study, we show that Wnt suppresses mitochondrial
      respiration and cytochrome C oxidase (COX) activity by inhibiting the expression
      of 3 COX subunits, namely, COXVIc, COXVIIa, and COXVIIc. We found that Wnt
      induced a glycolytic switch via increased glucose consumption and lactate
      production, with induction of pyruvate carboxylase (PC), a key enzyme of
      anaplerosis. In addition, Wnt-induced mitochondrial repression and glycolytic
      switching occurred through the canonical beta-catenin/T-cell factor 4/Snail
      pathway. Short hairpin RNA-mediated knockdown of E-cadherin, a regulator of EMT,
      repressed mitochondrial respiration and induced a glycolytic switch via Snail
      activation, indicating that EMT may contribute to Wnt/Snail regulation of
      mitochondrial respiration and glucose metabolism. Together, our findings provide
      a new function for Wnt/Snail signaling in the regulation of mitochondrial
      respiration (via COX gene expression) and glucose metabolism (via PC gene
      expression) in tumor growth and progression.

PMID- 22637726
TI  - CCR5 antagonist blocks metastasis of basal breast cancer cells.
AB  - The roles of the chemokine CCL5 and its receptor CCR5 in breast cancer
      progression remain unclear. Here, we conducted microarray analysis on 2,254 human
      breast cancer specimens and found increased expression of CCL5 and its receptor
      CCR5, but not CCR3, in the basal and HER-2 genetic subtypes. The subpopulation of
      human breast cancer cell lines found to express CCR5 displayed a functional
      response to CCL5. In addition, oncogene transformation induced CCR5 expression,
      and the subpopulation of cells that expressed functional CCR5 also displayed
      increased invasiveness. The CCR5 antagonists maraviroc or vicriviroc, developed
      to block CCR5 HIV coreceptor function, reduced in vitro invasion of basal breast
      cancer cells without affecting cell proliferation or viability, and maraviroc
      decreased pulmonary metastasis in a preclinical mouse model of breast cancer.
      Taken together, our findings provide evidence for the key role of CCL5/CCR5 in
      the invasiveness of basal breast cancer cells and suggest that CCR5 antagonists
      may be used as an adjuvant therapy to reduce the risk of metastasis in patients
      with the basal breast cancer subtype.

PMID- 22637735
TI  - Proliferative and nonproliferative lesions of the rat and mouse urinary system.
AB  - The INHAND Project (International Harmonization of Nomenclature and Diagnostic
      Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of
      Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and
      North America (STP) to develop an internationally accepted nomenclature for
      proliferative and nonproliferative lesions in laboratory animals. The purpose of
      this publication is to provide a standardized nomenclature for classifying
      lesions observed in the urinary tract of rats and mice. The standardized
      nomenclature of urinary tract lesions presented in this document is also
      available electronically on the Internet (http://www.goreni.org/). Sources of
      material included histopathology databases from government, academia, and
      industrial laboratories throughout the world. Content includes spontaneous
      developmental and aging lesions as well as those induced by exposure to test
      materials. A widely accepted and utilized international harmonization of
      nomenclature for urinary tract lesions in laboratory animals will decrease
      confusion among regulatory and scientific research organizations in different
      countries and provide a common language to increase and enrich international
      exchanges of information among toxicologists and pathologists.

PMID- 22637734
TI  - Identification of five novel modifier loci of Apc(Min) harbored in the BXH14
      recombinant inbred strain.
AB  - Every year thousands of people in the USA are diagnosed with small intestine and
      colorectal cancers (CRC). Although environmental factors affect disease etiology,
      uncovering underlying genetic factors is imperative for risk assessment and
      developing preventative therapies. Familial adenomatous polyposis is a heritable
      genetic disorder in which individuals carry germ-line mutations in the
      adenomatous polyposis coli (APC) gene that predisposes them to CRC. The Apc  ( 
      Min  ) mouse model carries a point mutation in the Apc gene and develops polyps
      along the intestinal tract. Inbred strain background influences polyp phenotypes
      in Apc  (  Min  ) mice. Several Modifier of Min (Mom) loci that alter tumor
      phenotypes associated with the Apc  (  Min  ) mutation have been identified to
      date. We screened BXH recombinant inbred (RI) strains by crossing BXH RI females
      with C57BL/6J (B6) Apc  (  Min  ) males and quantitating tumor phenotypes in
      backcross progeny. We found that the BXH14 RI strain harbors five modifier loci
      that decrease polyp multiplicity. Furthermore, we show that resistance is
      determined by varying combinations of these modifier loci. Gene interaction
      network analysis shows that there are multiple networks with proven gene-gene
      interactions, which contain genes from all five modifier loci. We discuss the
      implications of this result for studies that define susceptibility loci, namely
      that multiple networks may be acting concurrently to alter tumor phenotypes.
      Thus, the significance of this work resides not only with the modifier loci we
      identified but also with the combinations of loci needed to get maximal
      protection against polyposis and the impact of this finding on human disease
      studies.

PMID- 22637736
TI  - International harmonization of toxicologic pathology nomenclature: an overview
      and review of basic principles.
AB  - The International Harmonization of Nomenclature and Diagnostic Criteria for
      Lesions in Rats and Mice is a global project that is publishing criteria for both
      proliferative and nonproliferative changes in laboratory animals. This paper
      presents a set of general suggestions for terminology across systems. These
      suggestions include the use of diagnostic versus descriptive terms, modifiers,
      combination terms, and grading systems; and the use of thresholds, synonyms, and
      terminology for some processes that are common to several organ systems. The
      purpose of this paper is to help the reader understand some of the basic
      principles underlying the International Harmonization of Nomenclature and
      Diagnostic Criteria for Lesions in Rats and Mice process.

PMID- 22637737
TI  - Proliferative and nonproliferative lesions of the rat and mouse central and
      peripheral nervous systems.
AB  - Harmonization of diagnostic nomenclature used in the pathology analysis of
      tissues from rodent toxicity studies will enhance the comparability and
      consistency of data sets from different laboratories worldwide. The INHAND
      Project (International Harmonization of Nomenclature and Diagnostic Criteria for
      Lesions in Rats and Mice) is a joint initiative of four major societies of
      toxicologic pathology to develop a globally recognized nomenclature for
      proliferative and nonproliferative lesions in rodents. This article recommends
      standardized terms for classifying changes observed in tissues of the mouse and
      rat central (CNS) and peripheral (PNS) nervous systems. Sources of material
      include academic, government, and industrial histopathology databases from around
      the world. Covered lesions include frequent, spontaneous, and aging-related
      changes as well as principal toxicant-induced findings. Common artifacts that
      might be confused with genuine lesions are also illustrated. The neural
      nomenclature presented in this document is also available electronically on the
      Internet at the goRENI website (http://www.goreni.org/).

PMID- 22637738
TI  - Different types of resistance training in type 2 diabetes mellitus: effects on
      glycaemic control, muscle mass and strength.
AB  - BACKGROUND: Resistance training has become a mainstay of exercise training in
      type 2 diabetes mellitus (T2DM). However, it remains controversial whether
      hypertrophy resistance training (HRT) is superior to endurance resistance
      training (ERT) with regard to its effects on glycaemic control, muscle mass and
      strength. METHODS: Thirty-two patients with T2DM (13 men and 19 women; 64.8 +/-
      7.8 years) were randomly assigned to either eight weeks of HRT (n = 16; 2 sets,
      10-12 repetitions, 70% of the one-repetition maximum (1-RM)) or ERT (n = 16; 2
      sets, 25-30 repetitions, 40% 1-RM). In addition, all patients participated in
      aerobic exercise training (AET; 1 hour/day on 2 non-consecutive days/week; cycle
      ergometer; 70% of heart rate reserve). RESULTS: After eight weeks of
      intervention, there were time but not group effects for reduced glucose and
      fructosamine levels, weight, BMI, waist circumference, subcutaneous abdominal
      fat, resting heart rate, systolic and diastolic blood pressure; muscle mass of
      the arms and physical exercise capacity increased significantly. Significant time
      and group effects were documented for maximum strength of the chest, with a
      greater increase for HRT than ERT (p = 0.01). CONCLUSIONS: Specific maximal
      resistance training of the chest muscles led to superior gain in strength as
      compared to endurance resistance training. This, however, did not translate into
      superior values of glycaemic control, weight, waist circumference, muscle mass
      and physical work capacity, which all improved significantly by a similar
      magnitude in both groups. Since overall effects of both protocols were
      comparable, both may be offered to patients according to their personal
      preference.

PMID- 22637739
TI  - Secondary medical prevention after primary vascular surgery between 1996 and
      2006: a shift towards more evidence-based treatment.
AB  - OBJECTIVE: The implementation of evidence-based secondary medical prevention in
      peripheral arterial disease (PAD) patients has received increasing attention in
      recent years, but population-based data are sparse. This study examined the use
      of secondary medical prophylaxis in unselected symptomatic PAD patients in
      Denmark. DESIGN: A nationwide follow-up study based on individual-level record
      linkages of population-based healthcare registers was performed. PARTICIPANTS:
      All patients who underwent primary vascular reconstruction in Denmark between
      1996 and 2006 with a minimum of 6 months of follow-up were included (n = 16,492).
      METHODS: Data were obtained from prescriptions that were filled six months after
      primary vascular reconstruction (+/-90 days). The use of secondary medical
      prevention was examined according to calendar year and place of residence.
      RESULTS: The use of lipid-lowering drugs increased from 32.2% in 1996 to 76.1% in
      2006 (adjusted relative risk (RR) 1.95, 95% CI 1.81-2.10). The overall use of
      antihypertensive therapy was unchanged during the study period, but treatment
      shifted from diuretics/calcium antagonists towards angiotensin-converting enzyme
      inhibitors and angiotensin II receptor antagonists. The use of combination
      therapy (concomitant lipid-lowering, antiplatelet and any antihypertensive
      therapies) increased from 29.1% in 1996 to 67.6% in 2006 (adjusted RR 1.95, 95%
      CI 1.80-2.12). This shift in the use of secondary medical prevention was
      independent of sociodemographic and clinical factors. No substantial differences
      in pharmacological use based on place of residence were observed. CONCLUSION: The
      use of evidence-based secondary medical prevention, especially lipid-lowering
      drugs, increased substantially among symptomatic PAD patients in Denmark from
      1996 to 2006. However, recommendations in current clinical guidelines suggest
      that room for improvement remains.

PMID- 22637740
TI  - Importance of characteristics and modalities of physical activity and exercise in
      the management of cardiovascular health in individuals with cardiovascular
      disease (Part III).
AB  - The beneficial effect of exercise training and exercise-based cardiac
      rehabilitation on symptom-free exercise capacity,cardiovascular and skeletal
      muscle function, quality of life, general healthy lifestyle, and reduction of
      depressive symptoms and psychosocial stress is nowadays well recognized. However,
      it remains largely obscure, which characteristics of physical activity (PA) and
      exercise training--frequency, intensity, time (duration), type (mode), and volume
      (dose: intensity x duration) of exercise--are the most effective. The present
      paper, therefore, will deal with these exercise characteristics in the management
      of individuals with cardiovascular disease, i.e. coronary artery disease and
      chronic heart failure patients, but also in patients with congenital or valvular
      heart disease. Based on the current literature, and if sufficient evidence is
      available, recommendations from the European Association on Cardiovascular
      Prevention and Rehabilitation are formulated regarding frequency, intensity, time
      and type of PA, and safety aspects during exercise inpatients with cardiovascular
      disease. This paper is the third in a series of three papers, all devoted to the
      same theme: the importance of the exercise characteristics in the management of
      cardiovascular health. Part I is directed to the general population and Part II
      to individuals with cardiovascular risk factors. In general, PA recommendations
      and exercise training programmes for patients with coronary artery disease or
      chronic heart failure need to be tailored to the individual's exercise capacity
      and risk profile, with the aim to reach and maintain the individually highest
      fitness level possible and to perform endurance exercise training 30-60 min daily
      (3-5 days per week) in combination with resistance training 2-3 times a week.
      Because of the frequently reported dose-response relationship between training
      effect and exercise intensity, one should seek sufficiently high training
      intensities, although more scientific evidence on effect sizes and safety is
      warranted. At present, there is insufficient data to give more specific
      recommendations on type, dosage, and intensity of exercise in some other
      cardiovascular diseases, such as congenital heart disease, valve disease,
      cardiomyopathies, channelopathies, and patients with implanted devices.

PMID- 22637741
TI  - Importance of characteristics and modalities of physical activity and exercise in
      the management of cardiovascular health in individuals with cardiovascular risk
      factors: recommendations from the EACPR. Part II.
AB  - In a previous paper, as the first of a series of three on the importance of
      characteristics and modalities of physical activity (PA) and exercise in the
      management of cardiovascular health within the general population, we concluded
      that, in the population at large, PA and aerobic exercise capacity clearly are
      inversely associated with increased cardiovascular disease risk and all-cause and
      cardiovascular mortality and that a dose-response curve on cardiovascular outcome
      has been demonstrated in most studies. More and more evidence is accumulated that
      engaging in regular PA and exercise interventions are essential components for
      reducing the severity of cardiovascular risk factors, such as obesity and
      abdominal fat, high BP, metabolic risk factors, and systemic inflammation.
      However, it is less clear whether and which type of PA and exercise intervention
      (aerobic exercise, dynamic resistive exercise, or both) or characteristic of
      exercise (frequency, intensity, time or duration, and volume) would yield more
      benefit for each separate risk factor. The present paper, therefore, will review
      and make recommendations for PA and exercise training in the management of
      cardiovascular health in individuals with cardiovascular risk factors. The
      guidance offered in this series of papers is aimed at medical doctors, health
      practitioners, kinesiologists, physiotherapists and exercise physiologists,
      politicians, public health policy makers, and individual members of the public.
      Based on previous and the current literature overviews, recommendations from the
      European Association on Cardiovascular Prevention and Rehabilitation are
      formulated regarding type, volume, and intensity of PA and regarding appropriate
      risk evaluation during exercise in individuals with cardiovascular risk factors.

PMID- 22637742
TI  - Importance of characteristics and modalities of physical activity and exercise 
      in defining the benefits to cardiovascular  health within the general population:
      recommendations from the EACPR  (Part I).
AB  - Over the last decades, more and more evidence is accumulated that physical
      activity (PA) and exercise interventions are essential components in primary and
      secondary prevention for cardiovascular disease. However, it is less clear
      whether and which type of PA and exercise intervention (aerobic exercise, dynamic
      resistive exercise, or both) or characteristic of exercise (frequency, intensity,
      time or duration, and volume) would yield more benefit in achieving
      cardiovascular health. The present paper, as the first of a series of three, will
      make specific recommendations on the importance of these characteristics for
      cardiovascular health in the population at large. The guidance offered in this
      series of papers is aimed at medical doctors, health practitioners,
      kinesiologists, physiotherapists and exercise physiologists, politicians, public
      health policy makers, and the individual member of the public. Based on previous
      and the current literature, recommendations from the European Association on
      Cardiovascular Prevention and Rehabilitation are formulated regarding type,
      volume, and intensity of PA and exercise.

PMID- 22637743
TI  - Genome-wide gene-environment interaction analysis for asbestos exposure in lung
      cancer susceptibility.
AB  - Asbestos exposure is a known risk factor for lung cancer. Although recent genome
      wide association studies (GWASs) have identified some novel loci for lung cancer
      risk, few addressed genome-wide gene-environment interactions. To determine gene
      asbestos interactions in lung cancer risk, we conducted genome-wide gene
      environment interaction analyses at levels of single nucleotide polymorphisms
      (SNPs), genes and pathways, using our published Texas lung cancer GWAS dataset.
      This dataset included 317 498 SNPs from 1154 lung cancer cases and 1137 cancer
      free controls. The initial SNP-level P-values for interactions between genetic
      variants and self-reported asbestos exposure were estimated by unconditional
      logistic regression models with adjustment for age, sex, smoking status and pack
      years. The P-value for the most significant SNP rs13383928 was 2.17*10(-6), which
      did not reach the genome-wide statistical significance. Using a versatile gene
      based test approach, we found that the top significant gene was C7orf54, located
      on 7q32.1 (P = 8.90*10(-5)). Interestingly, most of the other significant genes
      were located on 11q13. When we used an improved gene-set-enrichment analysis
      approach, we found that  the Fas signaling pathway and the antigen processing and
      presentation pathway were most significant (nominal P < 0.001; false discovery
      rate < 0.05) among 250 pathways containing 17 572 genes. We believe that our
      analysis is a pilot study that first describes the gene-asbestos interaction in
      lung cancer risk at levels of SNPs, genes and pathways. Our findings suggest that
      immune function regulation-related pathways may be mechanistically involved in
      asbestos-associated lung cancer risk.

PMID- 22637744
TI  - Silencing of IkBbeta mRNA causes disruption of mitochondrial retrograde signaling
      and suppression of tumor growth in vivo.
AB  - A number of studies show that mitochondrial DNA (mtDNA) depletion and attendant
      activation of retrograde signaling induces tumor progression. We have reported
      previously that activation of a novel nuclear factor-Kappa B pathway is critical
      for the propagation of mitochondrial retrograde signaling, which induces both
      phenotypic and morphological changes in C2C12 myoblasts and A549 lung carcinoma
      cells. In this study, we investigated the role of stress-induced nuclear factor
      Kappa B in tumor progression in xenotransplanted mice. We used a retroviral
      system for the inducible expression of small interfering RNA against IkBalpha and
      IkBbeta mRNAs. Expression of small interfering RNA against IkBbeta markedly
      impaired tumor growth and invasive ability of mtDNA-depleted C2C12 myoblasts and
      also thwarted anchorage-independent growth of the cells. Knockdown of IkBalpha
      mRNA, however, did not have any modulatory effect in this cell system. Moreover,
      expression of small interfering RNA against IkBbeta reduced the expression of
      marker genes for retrograde signaling and tumor growth in xenografts of mtDNA
      depleted cells. Our findings demonstrate that IkBbeta is a master regulator of
      mitochondrial retrograde signaling pathway and that the retrograde signaling
      plays a role in tumor growth in vivo. In this regard, IkBbeta supports the
      tumorigenic potential of mtDNA-depleted C2C12 cells.

PMID- 22637746
TI  - Learning to manage COPD: a qualitative study of reasons for attending and not
      attending a COPD-specific self-management programme.
AB  - The aim of this article is to understand the reasons for attending a chronic
      obstructive pulmonary disease (COPD)-specific self-management (SM) programme and
      how attendance at such programmes might be improved. A total of 20 qualitative
      semistructured interviews were carried out with patients and with lay programme
      tutors involved in the Better Living with Long term Airways disease (BELLA) pilot
      trial. Thematic framework data analysis was used. Common reasons for participant
      attendance arising from patients and tutors include (1) desire to learn about SM,
      (2) social benefits of meeting others with COPD and (3) altruism. Patients'
      reasons for poor attendance include (1) being too ill or not feeling ill enough
      and (2) practical, physical and emotional barriers. Tutor's explanations for
      patients' poor attendance were (1) failure to accept their condition, (2) fear of
      making a change, (3) lack of adequate support, (4) guilt about smoking and (5)
      the 'scripted' nature of the course. Suggestions for improving programme
      participation included (1) having choice of several start dates, (2) minimal
      delay inviting participant onto courses, (3) planning for 'special needs'.
      Participation may be better amongst those who have accepted their condition or
      who are motivated towards improving their condition or to help others. Providing
      solutions for practical barriers may improve participation. However, alternatives
      to group-based interventions need to be developed for people with functional and
      emotional barriers to attendance.

PMID- 22637745
TI  - Re-expression of miR-200 by novel approaches regulates the expression of PTEN and
      MT1-MMP in pancreatic cancer.
AB  - Membrane type-1 matrix metalloproteinase (MT1-MMP) is often activated and
      expressed in tumor cells with significant invasive properties, and is associated
      with poor prognosis of patients. This could partly be due to deregulated
      expression of microRNAs (miRNAs) which regulates the expression of MT1-MMP and
      PTEN (phosphatase and tensin homolog) contributing to tumor invasion and
      metastasis. We initially compared the expression profile of miR-200 family, PTEN
      and MT1-MMP expression in six pancreatic cancer (PC) cell lines by qRT-PCR and
      western blot analysis. We found loss of expression of miR-200a, b and c in chemo
      resistant PC cell lines, which was correlated with loss of PTEN and over
      expression of MT1-MMP. Based on our initial findings, we chose BxPC-3, MIAPaCa-2
      and MIAPaCa-2-GR cells for further mechanistic studies We assessed the effect of
      two separate novel agents CDF (a synthetic analog of curcumin) and BR-DIM (a
      natural agent) on PC cells. The expression of miR-200 family and PTEN was
      significantly re-expressed whereas the expression of MT1-MMP was down-regulated
      by CDF and BR-DIM treatment. Forced over-expression or silencing of miR-200c,
      followed by either CDF or BR-DIM treatment of MIAPaCa-2 cells, altered the
      morphology of cells, wound-healing capacity, colony formation and the expression
      of MT1-MMP and PTEN. These results provide strong experimental evidence showing
      that the loss of miR-200 family and PTEN expression and increased level of MT1
      MMP leads to aggressive behavior of PC cells, which could be attenuated through
      re-expression of miR-200c by CDF and/or BR-DIM treatment, suggesting that these
      agents could be useful for PC treatment.

PMID- 22637747
TI  - Extending the course of intravenous antibiotics in adult patients with cystic
      fibrosis with acute pulmonary exacerbations.
AB  - Most severe pulmonary exacerbations (PExs) in adult patients with cystic fibrosis
      (CF) are treated with 2 week of intravenous (IV) antibiotics. At occasions, the
      treatment is extended. The morbidity and the cost of extending the treatment are
      considerable. Risk factors and the outcome of extending the course of treatment
      have not been formally investigated. This was a prospective study. Decision to
      extend the course of antibiotics was made in patients who were not deemed to have
      responded to the initial 14 days of treatment. Risk factors examined for
      extending the course were site of treatment (home or hospital), CF symptom score,
      body mass index (BMI), forced expiratory volume in the first second (FEV1) and C
      reactive protein (CRP) at days 1 and 14 of the treatment. The following outcome
      measures were assessed for PExs requiring prolongation of treatment: FEV1, BMI,
      CF symptom score, CRP and number of days until the following PExs. PExs that were
      treated with 14 day course were used for comparison. Of all the PExs, 22.9%
      needed extension of treatment beyond day 14. Compared with PExs needing 14 days
      of antibiotics, CF symptom score, FEV1 and CRP at day 14 were worse in those who
      had to have the course extended. Extending the course of IV antibiotics to 21
      days improved symptom score, but not any of the other outcome measures, including
      the number of days until the next PEx. Extending the course beyond 21 days did
      not result in improvement in any outcome measure. PExs in patients with worse
      lung disease and greater residual symptoms and lung inflammation at day 14 of
      antibiotic treatment were associated with the extension of the course of IV
      antibiotics. Prolonging the treatment to 21 days improved symptoms, but did not
      result in improvement in any other short-term or lung outcome measures.

PMID- 22637748
TI  - Smooth muscle cells and vascular diseases.

PMID- 22637749
TI  - ET block and the neointima: not the B, that is the answer.

PMID- 22637764
TI  - The debate around open-access publishing.

PMID- 22637750
TI  - Emerging role of G protein-coupled receptors in microvascular myogenic tone.
AB  - Blood flow autoregulation results from the ability of resistance arteries to
      reduce or increase their diameters in response to changes in intravascular
      pressure. The mechanism by which arteries maintain a constant blood flow to
      organs over a range of pressures relies on this myogenic response, which defines
      the intrinsic property of the smooth muscle to contract in response to stretch.
      The resistance to flow created by myogenic tone (MT) prevents tissue damage and
      allows the maintenance of a constant perfusion, despite fluctuations in arterial
      pressure. Interventions targeting MT may provide a more rational therapeutic
      approach in vascular disorders, such as hypertension, vasospasm, chronic heart
      failure, or diabetes. Despite its early description by Bayliss in 1902, the
      cellular and molecular mechanisms underlying MT remain poorly understood. We now
      appreciate that MT requires a complex mechanotransduction converting a physical
      stimulus (pressure) into a biological response (change in vessel diameter).
      Although smooth muscle cell depolarization and a rise in intracellular calcium
      concentration are recognized as cornerstones of the myogenic response, the role
      of wall strain-induced formation of vasoactive mediators is less well
      established. The vascular system expresses a large variety of Class 1 G protein
      coupled receptors (GPCR) activated by an eclectic range of chemical entities,
      including peptides, lipids, nucleotides, and amines. These messengers can
      function in blood vessels as vasoconstrictors. This review focuses on locally
      generated GPCR agonists and their proposed contributions to MT. Their interplay
      with pivotal G(q-11) and G(12-13) protein signalling is also discussed.

PMID- 22637765
TI  - Rethinking medical device regulation.

PMID- 22637766
TI  - Who do doctors work for?

PMID- 22637767
TI  - Wikipedia: encyclopaedia cardiologica.

PMID- 22637768
TI  - Can an electronic prescribing system detect doctors who are more likely to make a
      serious prescribing error?

PMID- 22637769
TI  - The NICE guidelines on the assessment of chest pain.

PMID- 22637771
TI  - Clinically led commissioning--joyous liberation or here we go again?

PMID- 22637770
TI  - Antisocial behaviour in children with and without callous-unemotional traits.
AB  - More than 15 years of research have documented behavioural differences between
      callous-unemotional and non-callous subtypes of children with antisocial
      behaviour. Recent studies also suggest that children with callous-unemotional
      traits may be genetically vulnerable to antisocial behaviour, while those without
      callous-unemotional traits appear to have primarily environmental aetiology to
      their antisocial behaviour. Furthermore neurocognitive profiles differ between
      antisocial children with and without callous-unemotional traits. While the former
      group appears emotionally under-reactive, particularly to others' distress, the
      latter group may be emotionally over-reactive, particularly to perceived threat.
      In this review we provide an overview of the current evidence base with regard to
      callous-unemotional and non-callous subgroups of children with antisocial
      behaviour and discuss the implications of the current evidence base for
      prevention and intervention. This overview selectively focuses on recent advances
      in this area of research, as well as earlier studies where these help set the
      research context.

PMID- 22637772
TI  - The advent of fair treatment allocation schedules in clinical trials during the
      19th and early 20th centuries.

PMID- 22637787
TI  - Implementing structured, multiprofessional medical ethical decision-making in a
      neonatal intensive care unit.
AB  - BACKGROUND: In neonatal intensive care, a child's death is often preceded by a
      medical decision. Nurses, social workers and pastors, however, are often excluded
      from ethical case deliberation. If multiprofessional ethical case deliberations
      do take place, participants may not always know how to perform to the fullest.
      SETTING: A level-IIID neonatal intensive care unit of a paediatric teaching
      hospital in the Netherlands. METHODS: Structured multiprofessional medical
      ethical decision-making (MEDM) was implemented to help overcome problems
      experienced. Important features were: all professionals who are directly involved
      with the patient contribute to MEDM; a five-step procedure is used: exploration,
      agreement on the ethical dilemma/investigation of solutions, analysis of
      solutions, decision-making, planning actions; meetings are chaired by an
      impartial ethicist. A 15-item questionnaire to survey staff perceptions on this
      intervention just before and 8 months after implementation was developed.
      RESULTS: Before and after response rates were 91/105 (87%) and 85/113 (75%).
      Factor analysis on the questionnaire suggested a four-factor structure:
      participants' role; structure of MEDM; content of ethical deliberation; and
      documentation of decisions/conclusions. Effect sizes were 1.67 (p<0.001), 0.69
      (p<0.001) and 0.40 (p<0.01) for the first three factors respectively, but only
      0.07 (p=0.65) for the fourth factor. Nurses' perceptions of improvement did not
      significantly exceed those of physicians. CONCLUSION: Professionals involved in
      ethical case deliberation perceived that the process of decision-making had
      improved; they were more positive about the structure of meetings, their own role
      and, to some extent, the content of ethical deliberation. Documentation of
      decisions/conclusions requires further improvement.

PMID- 22637937
TI  - An extract of Agaricus blazei Murill administered orally promotes immune
      responses in murine leukemia BALB/c mice in vivo.
AB  - PURPOSE: The edible mushroom (fungus) Agaricus blazei Murill (ABM) is a health
      food in many countries. Importantly, it has been shown to have antitumor and
      immune effects. There is no available information on ABM-affected immune
      responses in leukemia mice in vivo. Experimental Design. In this study, the
      authors investigated the immunopotentiating activities of boiled water-soluble
      extracts from desiccated ABM in WEHI-3 leukemia mice. The major characteristic of
      WEHI-3 leukemia mice are enlarged spleens and livers after intraperitoneal
      injection with murine leukemia WEHI-3 cells. Isolated T cells from spleens of ABM
      treated mice resulted in increased T-cell proliferation compared with the
      untreated control with concanavalin A stimulation. RESULTS: ABM decreased the
      spleen and liver weights when compared with WEHI-3 leukemia mice and this effect
      was a dose-dependent response. ABM promoted natural killer cell activity and
      phagocytosis by macrophage/monocytes in leukemia mice in a dose-dependent manner.
      ABM also enhanced cytokines such as interleukin (IL)-1beta, IL-6, and interferon
      gamma levels but reduced the level of IL-4 in WEHI-3 leukemia mice. Moreover, ABM
      increased the levels of CD3 and CD19 but decreased the levels of Mac-3 and CD11b
      in leukemia mice. CONCLUSIONS: The ABM extract is likely to stimulate immunocytes
      and regulate immune response in leukemia mice in vivo.

PMID- 22637938
TI  - Alterations in neural processing and psychopathology in children raised in
      institutions.
AB  - CONTEXT: Young children raised in institutional settings experience severe
      deprivation in social, emotional, and cognitive stimulation. Although this
      deprivation is likely to disrupt brain development in ways that increase the risk
      for psychopathology, neurodevelopmental mechanisms linking adverse early
      environments to psychopathology remain poorly understood. OBJECTIVE: To examine
      whether abnormalities in the neural processing of facial and emotional stimuli
      are related to the high rates of psychopathology observed among institutionally
      reared children. DESIGN, SETTING, AND PARTICIPANTS: Data were drawn from the
      Bucharest Early Intervention Project, a cohort of children raised in institutions
      in Romania and an age-matched sample of community control subjects. At entry to
      the study (mean age, 22 months), event-related potentials were used to measure
      neural processing in 2 tasks: familiar and unfamiliar faces (n=114) and facial
      displays of emotion (n=74). MAIN OUTCOME MEASURES: Psychiatric symptoms were
      assessed using the Preschool Age Psychiatric Assessment among children aged 54
      months. RESULTS: As previously reported, institutionally reared children had
      elevated symptoms of attention-deficit/hyperactivity disorder (ADHD), anxiety,
      depression, and disruptive behavior compared with control children, and peak
      amplitudes of the P100 and P700 in response to facial stimuli were blunted among
      institutionalized children compared with community children in both tasks.
      Current analyses reveal that children with reduced P100 and P700 amplitudes in
      response to facial stimuli exhibited higher levels of ADHD and anxiety symptoms.
      Peak amplitude of the P700 in response to facial stimuli significantly mediated
      the association between institutional rearing and ADHD symptoms at 54 months.
      CONCLUSION: Exposure to institutional rearing disrupts the P700, conferring risk
      for the onset of psychopathology. The high levels of ADHD symptoms among children
      exposed to early life deprivation may be attributable, in part, to abnormal
      patterns of neurodevelopment generated by these adverse rearing environments.

PMID- 22637967
TI  - Alterations in default mode network connectivity during pain processing in
      borderline personality disorder.
AB  - CONTEXT: Recent neuroimaging studies have associated activity in the default mode
      network (DMN) with self-referential and pain processing, both of which are
      altered in borderline personality disorder (BPD). In patients with BPD,
      antinociception has been linked to altered activity in brain regions involved in
      the cognitive and affective evaluation of pain. Findings in healthy subjects
      indicate that painful stimulation leads to blood oxygenation level-dependent
      signal decreases and changes in the functional architecture of the DMN.
      OBJECTIVES: To connect the previously separate research areas of DMN connectivity
      and altered pain perception in BPD and to explore DMN connectivity during pain
      processing in patients with BPD. DESIGN: Case-control study. SETTING: University
      hospital. PARTICIPANTS: Twenty-five women with BPD, including 23 (92%) with a
      history of self-harm, and 22 age-matched control subjects. INTERVENTIONS:
      Psychophysical assessment and functional magnetic resonance imaging during
      painful heat vs neutral temperature stimulation. MAIN OUTCOME MEASURE:
      Connectivity of DMN as assessed via independent component analysis and
      psychophysiological interaction analysis. RESULTS: Compared with control
      subjects, patients with BPD showed less integration of the left retrosplenial
      cortex and left superior frontal gyrus into the DMN. Higher BPD symptom severity
      and trait dissociation were associated with an attenuated signal decrease of the
      DMN in response to painful stimulation. During pain vs neutral, patients with BPD
      exhibited less posterior cingulate cortex seed region connectivity with the left
      dorsolateral prefrontal cortex. CONCLUSIONS: Patients with BPD showed significant
      alterations in DMN connectivity, with differences in spatial integrity and
      temporal characteristics. These alterations may reflect a different cognitive and
      affective appraisal of pain as less self-relevant and aversive as well as a
      deficiency in the switching between baseline and task-related processing. This
      deficiency may be related to everyday difficulties of patients with BPD in
      regulating their emotions, focusing mindfully on 1 task at a time, and
      efficiently shifting their attention from one task to another.

PMID- 22638001
TI  - Quality measures: necessary but not sufficient.

PMID- 22638003
TI  - Best practices: The Administrative Review Committee at New Hampshire Hospital: a
      one-year follow-up.
AB  - New Hampshire Hospital implemented an Administrative Review Committee (ARC), a
      best practice that provides a risk management process to mitigate potential
      liability for the hospital and clinicians treating high-profile, high-risk
      patients. This column reports on the first year of the ARC's operation, during
      which the committee reviewed 206 patients. The authors describe four patient
      groups and their distinguishing characteristics. The ARC is accepted by
      clinicians as an important venue to present high-risk clinical cases and to
      obtain risk management guidance and consultation. The committee has become an
      integral part of the hospital culture.

PMID- 22637968
TI  - The LPS2 mutation in TRIF is atheroprotective in hyperlipidemic low density
      lipoprotein receptor knockout mice.
AB  - Signaling through MyD88, an adaptor utilized by all TLRs except TLR3, is pro
      atherogenic; however, it is unknown whether signaling through TIR-domain
      containing adaptor-inducing interferon-beta (TRIF), an adaptor used only by TLRs
      3 and 4, is relevant to atherosclerosis. We determined that the TRIF(Lps2) lack
      of-function mutation was atheroprotective in hyperlipidemic low density
      lipoprotein (LDL) receptor knockout (LDLr(-/-)) mice. LDLr(-/-) mice were crossed
      with either TRIF(Lps2) or TLR3 knockout mice. After feeding an atherogenic diet
      for 10-15 wks, atherosclerotic lesions in the heart sinus and aorta were
      quantitated. LDLr(-/-) mice with TRIF(Lps2) were significantly protected from
      atherosclerosis. TRIF(Lps2) led to a reduction in cytokines secreted from
      peritoneal macrophages (M) in response to hyperlipidemia. Moreover, heart sinus
      valves from hyperlipidemic LDLr(-/-) TRIF(Lps2) mice had significantly fewer
      lesional M. However, LDLr(-/-) mice deficient in TLR3 showed some enhancement of
      disease. Collectively, these data suggest that hyperlipidemia resulting in
      endogenous activation of the TRIF signaling pathway from TLR4 leads to pro
      atherogenic events.

PMID- 22638004
TI  - Personal accounts: Bowling for Socks: residents are reminded that giving is
      receiving.

PMID- 22638005
TI  - Social support and risk of compulsory admission: part IV of the Amsterdam Study
      of Acute Psychiatry.
AB  - OBJECTIVE: Social support for patients with a mental illness has been associated
      with a lower rate of hospitalization. It is important to clarify the role played
      by a lack of social support as a possible predictor of emergency compulsory
      admission. METHODS: A random sample of 252 patients who were evaluated by two
      psychiatric emergency teams in Amsterdam from September 2004 to September 2006
      were interviewed approximately one month later about their social networks and
      social interactions. The number of emergency compulsory admissions was recorded
      for 244 patients during a two-year follow-up period after the interviews.
      RESULTS: Patients who lived alone had a higher risk of compulsory admission
      (p<=.05) and had fewer people in their social network (4.6 versus 6.1, p<=.001)
      compared with patients who lived with others. Among patients who lived alone, the
      percentage of patients with a compulsory admission was significantly higher among
      the patients with a high score for negative interactions than among patients with
      a low score (34% versus 13%, p<=.05). CONCLUSIONS: Of the social support
      variables, living alone proved to be the only predictor of emergency compulsory
      admission and readmission, and patients who lived alone had a smaller social
      network. A high level of negative social interactions increased the risk of
      compulsory admission among patients who lived alone.

PMID- 22638006
TI  - Implementing evidence-based psychotherapies in settings serving older adults:
      challenges and solutions.
AB  - This Open Forum addresses challenges--insurance limitations, staff and setting
      limitations, and training and sustainability issues--in the implementation of
      psychotherapy interventions in settings serving older adults and provides
      solutions for ensuring that they have access to effective mental health services.
      There is considerable movement toward developing the geriatric mental health
      workforce, and it is important that these efforts include a discussion of
      implementation issues with regard to evidence-based psychotherapies as they are
      provided in services for aging populations.

PMID- 22638007
TI  - Group cognitive-behavioral therapy for clients with major depression in
      residential substance abuse treatment.
AB  - OBJECTIVE: The BRIGHT (Building Recovery by Improving Goals, Habits, and
      Thoughts) study was a community-based effectiveness trial that compared
      residential substance abuse treatment with residential treatment plus group
      cognitive-behavioral therapy (CBT)for depression. This brief report focuses on
      the subgroup of participants with major depression. METHODS: The authors used a
      quasi-experimental design and an intent-to-treat analysis. Out of 299
      participants enrolled, 135 had major depression. Primary outcomes were change in
      depression symptoms, mental health functioning, and days of alcohol use and
      problematic substance use. RESULTS: At the three-month follow-up, participants
      with major depression reported less severe depression and better functioning,
      compared with participants with major depression who received usual care. At six
      months, functioning continued to be higher and problem substance use was lower.
      CONCLUSIONS: Group CBT was an effective treatment for major depression for
      clients in residential substance abuse treatment. These results extend the
      effectiveness of group CBT for major depression to a new setting, patient
      population, and type of provider.

PMID- 22638008
TI  - Care seeking and beliefs about the cause of mental illness among Nigerian
      psychiatric patients and their families.
AB  - OBJECTIVE: This study examined treatment seeking by 219 psychiatric patients at a
      teaching hospital in Kano, Nigeria. METHODS: Patients or their families were
      interviewed about the types of mental health healers that patients saw before
      seeking conventional psychiatric treatment and beliefs about the causes of the
      illness. RESULTS: The length of illness before the psychiatric consultation was
      4.5 years, and 99 (45%) respondents reported that patients had previously sought
      religious healing. A majority of respondents (N=128, 59%) attributed the illness
      to supernatural forces. Up to 68% and 75% of respondents who believed in a
      medical or genetic cause of illness, respectively, reported seeking a psychiatric
      consultation within six months of onset, and about 70% who believed in
      supernatural forces reported seeking psychiatric consultation five years after
      onset or later (p<.05). CONCLUSIONS: Mental health planners should educate
      alternative mental health healers and integrate them in the care of mental
      illness.

PMID- 22638009
TI  - SAMHSA's latest report on the nation's mental health.

PMID- 22638010
TI  - NASMHPD outlines steps toward integration of care.

PMID- 22638012
TI  - Serotonin and the neural processing of facial emotions in adults with autism: an
      fMRI study using acute tryptophan depletion.
AB  - CONTEXT: People with autism spectrum disorders (ASDs) have lifelong deficits in
      social behavior and differences in behavioral as well as neural responses to
      facial expressions of emotion. The biological basis to this is incompletely
      understood, but it may include differences in the role of neurotransmitters such
      as serotonin, which modulate facial emotion processing in health. While some
      individuals with ASD have significant differences in the serotonin system, to our
      knowledge, no one has investigated its role during facial emotion processing in
      adults with ASD and control subjects using acute tryptophan depletion (ATD) and
      functional magnetic resonance imaging. OBJECTIVE: To compare the effects of ATD
      on brain responses to primary facial expressions of emotion in men with ASD and
      healthy control subjects. DESIGN: Double-blind, placebo-controlled, crossover
      trial of ATD and functional magnetic resonance imaging to measure brain activity
      during incidental processing of disgust, fearful, happy, and sad facial
      expressions. SETTING: Institute of Psychiatry, King's College London, and South
      London and Maudsley National Health Service Foundation Trust, England.
      PARTICIPANTS: Fourteen men of normal intelligence with autism and 14 control
      subjects who did not significantly differ in sex, age, or overall intelligence.
      MAIN OUTCOME MEASURES: Blood oxygenation level-dependent response to facial
      expressions of emotion. RESULTS: Brain activation was differentially modulated by
      ATD depending on diagnostic group and emotion type within regions of the social
      brain network. For example, processing of disgust faces was associated with
      interactions in medial frontal and lingual gyri, whereas processing of happy
      faces was associated with interactions in middle frontal gyrus and putamen.
      CONCLUSIONS: Modulation of the processing of facial expressions of emotion by
      serotonin significantly differs in people with ASD compared with control
      subjects. The differences vary with emotion type and occur in social brain
      regions that have been shown to be associated with group differences in serotonin
      synthesis/receptor or transporter density.

PMID- 22638070
TI  - Research resource: Genome-wide profiling of progesterone receptor binding in the
      mouse uterus.
AB  - Progesterone (P4) signaling through its nuclear transcription factor, the
      progesterone receptor (PR), is essential for normal uterine function. Although
      deregulation of PR-mediated signaling is known to underscore uterine dysfunction
      and a number of endometrial pathologies, the early molecular mechanisms of this
      deregulation are unclear. To address this issue, we have defined the genome-wide
      PR cistrome in the murine uterus using chromatin immunoprecipitation (ChIP)
      followed by massively parallel sequencing (ChIP-seq). In uteri of ovariectomized
      mice, we identified 6367 PR-binding sites in the absence of P4 ligand; however,
      this number increased at nearly 3-fold (18,432) after acute P4 exposure. Sequence
      analysis revealed that approximately 73% of these binding sites contain a
      progesterone response element or a half-site motif recognized by the PR. Many
      previously identified P4 target genes known to regulate uterine function were
      found to contain PR-binding sites, confirming the validity of our methodology.
      Interestingly, when the ChIP-seq data were coupled with our microarray expression
      data, we identified a novel regulatory role for uterine P4 in circadian rhythm
      gene expression, thereby uncovering a hitherto unexpected new circadian biology
      for P4 in this tissue. Further mining of the ChIP-seq data revealed Sox17 as a
      direct transcriptional PR target gene in the uterus. As a member of the Sox
      transcription factor family, Sox17 represents a potentially novel mediator of PR
      action in the murine uterus. Collectively, our first line of analysis of the
      uterine PR cistrome provides the first insights into the early molecular
      mechanisms that underpin normal uterine responsiveness to acute P4 exposure.
      Future analysis promises to reveal the PR interactome and, in turn, potential
      therapeutic targets for the diagnosis and/or treatment of endometrial
      dysfunction.

PMID- 22638071
TI  - Vitamin D receptor signaling inhibits atherosclerosis in mice.
AB  - Although vitamin D has been implicated in cardiovascular protection, few studies
      have addressed the role of vitamin D receptor (VDR) in atherosclerosis. Here we
      investigate the effect of inactivation of the VDR signaling on atherogenesis and
      the antiatherosclerotic mechanism of vitamin D. Low density lipoprotein receptor
      (LDLR)(-/-)/VDR(-/-) mice exhibited site-specific accelerated atherogenesis,
      accompanied by increases in adhesion molecules and proinflammatory cytokines in
      the aorta and cholesterol influx in macrophages. Macrophages showed marked renin
      up-regulation in the absence of VDR, and inhibition of renin by aliskiren reduced
      atherosclerosis in LDLR(-/-)/VDR(-/-) mice, suggesting that the renin-angiotensin
      system (RAS) promotes atherosclerosis in the absence of VDR. LDLR(-/-) mice
      receiving LDLR(-/-)/VDR(-/-) BMT developed larger lesions than LDLR(-/-) BMT
      controls. Moreover, LDLR(-/-) mice receiving Rag-1(-/-)/VDR(-/-) BMT, which were
      unable to generate functional T and B lymphocytes, still had more severe
      atherosclerosis than Rag-1(-/-) BMT controls, suggesting a critical role of
      macrophage VDR signaling in atherosclerotic suppression. Aliskiren treatment
      eliminated the difference in lesions between Rag-1(-/-)/VDR(-/-) BMT and Rag-1(-/
      ) BMT recipients, indicating that local RAS activation in macrophages contributes
      to the enhanced atherogenesis seen in Rag-1(-/-)/VDR(-/-) BMT mice. Taken
      together, these observations provide evidence that macrophage VDR signaling, in
      part by suppressing the local RAS, inhibits atherosclerosis in mice.

PMID- 22638072
TI  - Research resource: A genome-wide study identifies potential new target genes for
      POU1F1.
AB  - The pituitary transcription factor POU1F1 is required for the differentiation of
      lactotrope, thyrotrope, and somatotrope cells. Its expression is maintained in
      the adult and is crucial for the expression of prolactin, GH, and TSHbeta
      subunit. Different studies indicated that POU1F1 could also have other functions
      in these cells. The identification of new targets of this factor could be useful
      to obtain a better understanding of these functions. To address this question we
      combined data obtained from expression microarrays and from chromatin
      immunoprecipitation (ChIP)-chips. Gene expression microarray assays were used to
      detect genes that have their expression modified in somatolactotrope GH4C1 cells
      by the expression of a dominant-negative form of POU1F1, POU1F1(R271W), and led
      to the identification of 1346 such genes. ChIP-chip experiments were performed
      from mouse pituitaries and identified 1671 POU1F1-binding sites in gene-promoter
      regions. Intersecting the gene expression and the ChIP-chip data yielded 121
      potential new direct targets. The initial set of 1346 genes identified using the
      microarrays, as well as the 121 potential new direct targets, were analyzed with
      DAVID bioinformatics resource for gene ontology term enrichment and cluster. This
      analysis revealed enrichment in different terms related to protein synthesis and
      transport, to apoptosis, and to cell division. The present study represents an
      integrative genome-wide approach to identify new target genes of POU1F1 and
      downstream networks controlled by this factor.

PMID- 22638077
TI  - A novel mutation in the mitochondrial DNA cytochrome b gene (MTCYB) in a patient
      with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes
      syndrome.
AB  - Mutations in the mitochondrial DNA cytochrome b gene (MTCYB) have been commonly
      associated with isolated mitochondrial myopathy and exercise intolerance, rarely
      with multisystem disorders, and only once with a parkinsonism/mitochondrial
      encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) overlap
      syndrome. Here, we describe a novel mutation (m.14864 T>C) in MTCYB in a 15-year
      old girl with a clinical history of migraines, epilepsy, sensorimotor neuropathy,
      and strokelike episodes, a clinical picture reminiscent of MELAS.  The mutation,
      which changes a highly conserved cysteine to arginine at amino acid position 40
      of cytochrome b, was heteroplasmic in muscle, blood, fibroblasts, and urinary
      sediment from the patient but absent in accessible tissues from her asymptomatic
      mother. This case demonstrates that MTCYB must be included in the already long
      list of mitochondrial DNA genes that have been associated with the MELAS
      phenotype.

PMID- 22638073
TI  - Biasing the prostaglandin F2alpha receptor responses toward EGFR-dependent
      transactivation of MAPK.
AB  - The G protein-coupled prostaglandin F2alpha (PGF2alpha) receptor [F prostanoid
      (FP) receptor] has been implicated in many physiological events including
      cardiovascular, respiratory, immune, reproductive, and endocrine responses.
      Binding of PGF2alpha to FP receptor elicits inositol production and protein
      kinase C-dependent MAPK activation through Galpha(q) coupling. Here we report
      that AL-8810, previously characterized as an orthosteric antagonist of PGF2alpha
      dependent, Galpha(q)-mediated signaling, potently activates ERK1/2 in a protein
      kinase C-independent manner. Rather, AL-8810 promoted ERK1/2 activation via an
      epidermal growth factor receptor transactivation mechanism in both human
      embryonic kidney 293 cells and in the MG-63 osteoblast-like cells, which express
      endogenous FP receptors. Neither AL-8810- nor PGF2alpha-mediated stimulation of
      FP receptor promoted association with beta-arrestins, suggesting that MAPK
      activation induced by these ligands is independent of beta-arrestin's signaling
      scaffold functions. Interestingly, the spatiotemporal activation of ERK1/2
      promoted by AL-8810 and PGF2alpha showed almost completely opposite responses in
      the nucleus and the cytosol. Finally, using [(3)H]thymidine incorporation, we
      noted differential regulation of PGF2alpha- and AL-8810-induced cell
      proliferation in MG-63 cells. This study reveals, for the first time, the
      signaling biased nature of FP receptor orthosteric ligands toward MAPK signaling.
      Our findings on the specific patterns of ERK1/2 activation promoted by FP
      receptor ligands may help dissect the distinct roles of MAPK in FP receptor
      dependent physiological responses.

PMID- 22638078
TI  - Idiopathic harlequin syndrome: a pediatric case.
AB  - Harlequin syndrome, Harlequin sign, Holmes-Adie syndrome, and Ross syndrome lie
      on a spectrum of partial dysautonomias affecting facial sudomotor, vasomotor, and
      pupillary responses. These syndromes have imprecise clinical boundaries and
      overlap syndromes are known. We report a 9-year-old girl who presented with
      anhidrosis over the right half of her face and the left side of her body, with
      compensatory hyperhidrosis on the contralateral side. She was noted to have
      bilateral tonic pupils and normal muscle stretch reflexes with other features
      suggestive of autonomic dysfunction. Investigations to rule out secondary causes
      were noncontributory. Her clinical presentation can be categorized as partial
      overlap between Harlequin syndrome and Holmes-Adie syndrome.

PMID- 22638108
TI  - Early to intermediate steps of tumor embolic formation involve specific
      proteolytic processing of E-cadherin regulated by Rab7.
AB  - The lymphovascular embolus is an enigmatic entity adept at metastatic
      dissemination and chemotherapy resistance. Using MARY-X, a human breast cancer
      xenograft that exhibits florid lymphovascular emboli in mice and spheroids in
      vitro, we established a model where the in vitro transition stages from minced
      tumoral aggregates to well-formed spheroids served as a surrogate for in vivo
      emboli formation. MARY-X well-formed spheroids and emboli exhibited strong
      similarity of expression. The aggregate-to-spheroid transition stages were
      characterized by increased ExoC5, decreased Hgs and Rab7, increased calpains,
      increased full-length E-cadherin (E-cad/FL), and the transient appearance of E
      cad/NTF2, a 95 kDa E-cadherin fragment and increased Notch3icd (N3icd), the
      latter two fragments produced by increased gamma-secretase. Both transient and
      permanent knockdowns of Rab7 in MCF-7 cells increased protein but not
      transcription of E-cad/FL and resulted in the de novo appearance of E-cad/NTF2,
      the presence of nuclear E-cad/CTF2, and increased Notch1icd (N1icd).
      Overexpression of Rab7 conversely decreased E-cad/FL, gamma-secretase (PS1/NTF),
      and E-cad/NTF2. Overexpression of calpains did not alter PS1/NTF but decreased E
      cad/FL and E-cad/NTF2 and increased N1icd. Well-formed spheroids showed increased
      Rab7, absent E-cad/NTF2, decreased PS1/NTF, increased E-cad/NTF1, and increased
      N3icd, the latter two fragments being the direct and indirect consequences,
      respectively, of increased calpains (calpain 1 and calpain 2). Inhibition of
      calpains decreased E-cad/NTF1 but increased E-cad/NTF2 showing that calpains
      compete with gamma-secretase (PS1) for closely located cleavage/binding sites on
      E-cadherin and that increased calpains can shuttle even decreased levels of gamma
      secretase to Notch 3, resulting in increased Notch 3 signaling in the well-formed
      spheroids.

PMID- 22638145
TI  - Sustained remission of multicentric Castleman disease in children treated with
      tocilizumab, an anti-interleukin-6 receptor antibody.
AB  - Multicentric Castleman Disease (MCD) is an idiopathic lymphoproliferative
      disorder, reported exceptionally in children and generally believed to be an
      autoinflammatory disease resulting in an increase of interleukin-6 secretion.
      Previous studies in adult patients suggested a beneficial role of the anti
      interleukin-6 receptor antibody tocilizumab on the clinical and biologic disease
      manifestations of MCD. Here, we describe the efficacy and safety of tocilizumab
      in two children with MCD, which was diagnosed on the basis of clinical and
      histologic findings. In both cases, tocilizumab was administered intravenously at
      a dose of 8 mg/kg every 2 weeks. The tocilizumab treatment alleviated fever and
      restored growth rate in both patients. The patients' hypergammaglobulinemia, high
      C-reactive protein, and high erythrocyte sedimentation rates normalized
      simultaneously. Nevertheless, splenomegaly persisted in the first patient, and a
      secondary hepatic node appeared in the second patient. The side effects,
      essentially sustained thrombocytopenia, were mild in both cases. For the first
      patient, following an initial 10-month period, the interval between infusions was
      increased. This patient benefited from sustained remission for a period of 3
      years. Tocilizumab was effective and safe in these two children with MCD.

PMID- 22638210
TI  - Inhibition of IDO1 suppresses cyclooxygenase-2 and matrix metalloproteinase-9
      expression and decreases proliferation, adhesion and invasion of endometrial
      stromal cells.
AB  - Indoleamine 2,3-dioxygenase-1 (IDO1) is an intracellular enzyme that catalyses
      essential amino acid tryptophan along the kynurenine pathway. The aim of this
      study was to determine the impact of IDO1 expression on the biological
      characteristic of the endometrial stromal cells (ESCs). IDO1, cyclooxygenase-2
      (COX-2) and matrix metalloproteinases (MMPs) in endometriotic ectopic stromal
      cells, endometriosis-derived eutopic stromal cells and normal ESCs (control) were
      detected by the in-cell Western analysis. After being treated with
      lipopolysaccharide, levo-1-methyl-tryptophan (L-1-MT) alone or a combination, a
      comparative analysis of the above protein expression was evaluated. The effects
      of IDO1 on ESCs proliferation, adhesion and invasion were detected through ELISA,
      adhesion assay and Matrigel invasion assay, respectively. The results showed
      that, contrary to healthy ESCs from control women, the expression of IDO1 was
      significantly higher in eutopic and ectopic ESCs obtained from women with
      endometriosis. Inhibition of IDO1 by L-1-MT suppressed the expression of COX-2
      and MMP-9 in ESCs. It could also decrease the ESCs proliferation, adhesion and
      invasion, while stimulating ESCs decidualization. Thus, IDO1 is possibly involved
      in endometriosis pathogenesis via promoting COX-2 and MMP-9 expression and
      regulation of ESCs biological characteristics. The information may be useful for
      developing a new therapeutic strategy for endometriosis.

PMID- 22638269
TI  - gC1qR expression in normal and pathologic human tissues: differential expression
      in tissues of epithelial and mesenchymal origin.
AB  - The gC1qR (i.e., gC1q receptor, gC1q binding protein, p32, p33) is a
      multifunctional cellular protein that interacts with components of the
      complement, kinin, and coagulation cascades and select microbial pathogens.
      Enhanced gC1qR expression has been reported in adenocarcinomas arising in a
      variety of organs. The present study compared gC1qR expression in normal,
      inflammatory, dysplastic, and malignant tissue of epithelial and mesenchymal
      origin. gC1qR expression was visualized in tissue sections by
      immunohistochemistry using the 60.11 monoclonal antibody (i.e., IgG(1) mouse
      monoclonal antibody directed against gC1qR) and the UltraVision LP Detection
      System. Sections were counterstained with hematoxylin and examined by light
      microscopy. Strongest gC1qR expression was noted in epithelial tumors of breast,
      prostate, liver, lung, and colon, as well as in squamous and basal cell carcinoma
      of the skin. However, increased gC1qR staining was appreciated also in
      inflammatory and proliferative lesions of the same cell types, as well as in
      normal continuously dividing cells. In contrast, tumors of mesenchymal origin
      generally stained weakly, with the exception of osteoblasts, which stained in
      both benign and malignant tissues. The data suggest that increased gC1qR
      expression may be a marker of benign and pathologic cell proliferation,
      particularly in cells of epithelial origin, with potential diagnostic and
      therapeutic applications.

PMID- 22638109
TI  - State of the science: an update on renal cell carcinoma.
AB  - Renal cell carcinomas (RCC) are emerging as a complex set of diseases that are
      having a major socioeconomic impact and showing a continued rise in incidence
      throughout the world. As the field of urologic oncology faces these trends,
      several major genomic and mechanistic discoveries are altering our core
      understanding of this multitude of cancers, including several new rare subtypes
      of renal cancers. In this review, these new findings are examined and placed in
      the context of the well-established association of clear cell RCC (ccRCC) with
      mutations in the von Hippel-Lindau (VHL) gene and resultant aberrant hypoxia
      inducible factor (HIF) signaling. The impact of novel ccRCC-associated genetic
      lesions on chromatin remodeling and epigenetic regulation is explored. The
      effects of VHL mutation on primary ciliary function, extracellular matrix
      homeostasis, and tumor metabolism are discussed. Studies of VHL proteostasis,
      with the goal of harnessing the proteostatic machinery to refunctionalize mutant
      VHL, are reviewed. Translational efforts using molecular tools to elucidate
      discriminating features of ccRCC tumors and develop improved prognostic and
      predictive algorithms are presented, and new therapeutics arising from the
      earliest molecular discoveries in ccRCC are summarized. By creating an integrated
      review of the key genomic and molecular biological disease characteristics of
      ccRCC and placing these data in the context of the evolving therapeutic
      landscape, we intend to facilitate interaction among basic, translational, and
      clinical researchers involved in the treatment of this devastating disease, and
      accelerate progress toward its ultimate eradication.

PMID- 22638306
TI  - Removal of industry-sponsored formula sample packs from the hospital: does it
      make a difference?
AB  - BACKGROUND: Most US hospitals distribute industry-sponsored formula sample packs.
      No research has examined outcomes associated with sample pack removal as part of
      a hospital intervention to eliminate sample distribution postpartum. OBJECTIVE:
      To examine prospectively hospital-based and breastfeeding outcomes associated
      with removal of industry-sponsored formula sample packs from the hospital.
      METHODS: We enrolled mothers postpartum at Cooper University Hospital, an urban
      New Jersey hospital, in 2009-2010. For the first 6 months, all women received
      industry-sponsored formula samples packs (control group); for the next 6 months,
      all postpartum women received hospital-sponsored bags with no formula at source
      (intervention group). Research assistants blinded to the design called subjects
      weekly for 10 weeks to determine feeding practices. RESULTS: We enrolled 527
      breastfeeding women (284 control; 243 intervention). At 10 weeks postpartum, 82%
      of control and 36% of intervention women (P < .001) reported receiving formula in
      the "diaper discharge bag." Kaplan-Meyer curves for any breastfeeding showed the
      intervention was associated with increased breastfeeding (P = .03); however,
      exclusive breastfeeding was not significantly different between intervention and
      controls (P = .46). In post hoc analysis, receiving no take-home formula in
      bottles from the hospital was associated with increased exclusive breastfeeding
      in control (P = .02) and intervention (P = .03) groups at 10 weeks. CONCLUSION:
      Although the hospital-branded replacement contained no formula at source, many
      women reported receiving bottles of formula from the hospital. Change in practice
      to remove industry-sponsored formula sample packs was associated with increased
      breastfeeding over 10 weeks, but the intervention may have had a greater impact
      had it not been contaminated.

PMID- 22638494
TI  - Guilt-selective functional disconnection of anterior temporal and subgenual
      cortices in major depressive disorder.
AB  - CONTEXT: Proneness to overgeneralization of self-blame is a core part of
      cognitive vulnerability to major depressive disorder (MDD) and remains dormant
      after remission of symptoms. Current neuroanatomical models of MDD, however,
      assume general increases of negative emotions and are unable to explain biases
      toward emotions entailing self-blame (eg, guilt) relative to those associated
      with blaming others (eg, indignation). Recent functional magnetic resonance
      imaging (fMRI) studies in healthy participants have shown that moral feelings
      such as guilt activate representations of social meaning within the right
      superior anterior temporal lobe (ATL). Furthermore, this area was selectively
      coupled with the subgenual cingulate cortex and adjacent septal region (SCSR)
      during the experience of guilt compared with indignation. Despite its
      psychopathological importance, the functional neuroanatomy of guilt in MDD is
      unknown. OBJECTIVE: To use fMRI to test the hypothesis that, in comparison with
      control individuals, participants with remitted MDD exhibit guilt-selective SCSR
      ATL decoupling as a marker of deficient functional integration. DESIGN: Case
      control study from May 1, 2008, to June 1, 2010. SETTING: Clinical research
      facility. PARTICIPANTS: Twenty-five patients with remitted MDD (no medication in
      16 patients) with no current comorbid Axis I disorders and 22 controls with no
      personal or family history of MDD. MAIN OUTCOME MEASURES: Between-group
      difference of ATL coupling with a priori SCSR region of interest for guilt vs
      indignation. RESULTS: We corroborated the prediction of a guilt-selective
      reduction in ATL-SCSR coupling in MDD vs controls (familywise error-corrected
      P=.001 over the region of interest) and revealed additional medial frontopolar,
      right hippocampal, and lateral hypothalamic areas of decoupling while controlling
      for medication status and intensity of negative emotions. Lower levels of ATL
      SCSR coupling were associated with higher scores on a validated measure of
      overgeneralized self-blame (67-item Interpersonal Guilt Questionnaire).
      CONCLUSIONS: Vulnerability to MDD is associated with temporofrontolimbic
      decoupling that is selective for self-blaming feelings. This provides the first
      neural mechanism ofMDD vulnerability that accounts for self-blaming biases.

PMID- 22638547
TI  - Trends in childhood type 1 diabetes incidence in Europe during 1989-2008:
      evidence of non-uniformity over time in rates of increase.
AB  - AIMS/HYPOTHESIS: The aim of the study was to describe 20-year incidence trends
      for childhood type 1 diabetes in 23 EURODIAB centres and compare rates of
      increase in the first (1989-1998) and second (1999-2008) halves of the period.
      METHODS: All registers operate in geographically defined regions and are based on
      a clinical diagnosis. Completeness of registration is assessed by capture
      recapture methodology. Twenty-three centres in 19 countries registered 49,969 new
      cases of type 1 diabetes in individuals diagnosed before their 15th birthday
      during the period studied. RESULTS: Ascertainment exceeded 90% in most registers.
      During the 20-year period, all but one register showed statistically significant
      changes in incidence, with rates universally increasing. When estimated
      separately for the first and second halves of the period, the median rates of
      increase were similar: 3.4% per annum and 3.3% per annum, respectively. However,
      rates of increase differed significantly between the first half and the second
      half for nine of the 21 registers with adequate coverage of both periods; five
      registers showed significantly higher rates of increase in the first half, and
      four significantly higher rates in the second half. CONCLUSIONS/INTERPRETATION:
      The incidence rate of childhood type 1 diabetes continues to rise across Europe
      by an average of approximately 3-4% per annum, but the increase is not
      necessarily uniform, showing periods of less rapid and more rapid increase in
      incidence in some registers. This pattern of change suggests that important risk
      exposures differ over time in different European countries. Further time trend
      analysis and comparison of the patterns in defined regions is warranted.

PMID- 22638548
TI  - Relationship between HbA1c levels and risk of cardiovascular adverse outcomes and
      all-cause mortality in overweight and obese cardiovascular high-risk women and
      men with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: The optimal HbA(1c) concentration for prevention of
      macrovascular complications and deaths in obese cardiovascular high-risk patients
      with type 2 diabetes remains to be established and was therefore studied in this
      post hoc analysis of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial, which
      enrolled overweight and obese patients with type 2 diabetes and/or cardiovascular
      disease. METHODS: HRs for meeting the primary endpoint (nonfatal myocardial
      infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death)
      and all-cause mortality were analysed using Cox regression models. RESULTS: Of
      8,252 patients with type 2 diabetes included in SCOUT, 7,479 had measurements of
      HbA(1c) available at baseline (i.e. study randomisation). Median age was 62 years
      (range 51-86 years), median BMI was 34.0 kg/m(2) (24.8-65.1 kg/m(2)) and 44% were
      women. The median HbA(1c) concentration was 7.2% (3.8-15.9%) (55 mmol/l [18-150
      mmol/l]) and median diabetes duration was 7 years (0-57 years). For each 1
      percentage point HbA(1c) increase, the adjusted HR for the primary endpoint was
      1.17 (95% CI 1.11, 1.23); no differential sex effect was observed (p = 0.12 for
      interaction). In contrast, the risk of all-cause mortality was found to be
      greater in women than in men: HR 1.22 (1.10, 1.34) vs 1.12 (1.04, 1.20) for each
      1 percentage point HbA(1c) increase (p = 0.02 for interaction). There was no
      evidence of increased risk associated with HbA(1c) <= 6.4% (<= 46 mmol/l).
      Glucose-lowering treatment regimens, diabetes duration or a history of
      cardiovascular disease did not modify the associations.
      CONCLUSIONS/INTERPRETATION: In overweight, cardiovascular high-risk patients with
      type 2 diabetes, increasing HbA(1c) concentrations were associated with
      increasing risks of cardiovascular adverse outcomes and all-cause mortality.

PMID- 22638550
TI  - A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1
      transformed T cells serves as a T helper epitope.
AB  - Human T cell leukemia virus type 1 (HTLV-1) induced adult T cell
      leukemia/lymphoma (ATLL) is usually a fatal lymphoproliferative malignant
      disease. Thus, the enhancement of T cell immunity to ATLL through the development
      of therapeutic vaccines using characterized T cell peptide epitopes could be of
      value. We isolated and characterized HLA-DR-bound peptides from HTLV-1
      transformed T cells by fractionating on reverse-phase high performance liquid
      chromatography and Edman NH(2)-terminal sequencing and were able to identify five
      independent peptide sequences. One of the identified peptide sequences
      corresponded to a fragment of the human interleukin-9 receptor alpha (IL
      9Ralpha), which is commonly expressed by HTLV-1-infected T cell lymphoma cells.
      Using a synthetic peptide corresponding to the identified IL-9Ralpha sequence, we
      generated antigen-specific CD4 helper T lymphocytes in vitro, which were
      restricted by HLA-DR15 or HLA-DR53 molecules and could recognize and kill HTLV
      1+, IL-9Ralpha+ T cell lymphoma cells. These results indicate that IL-9Ralpha
      functions as T cell leukemia/lymphoma-associated antigen for CD4 T cells and that
      synthetic peptides such as the one described here could be used for T cell-based
      immunotherapy against IL-9Ralpha positive ATLL.

PMID- 22638549
TI  - Predominant role of active versus facilitative glucose transport for glucagon
      like peptide-1 secretion.
AB  - AIMS/HYPOTHESIS: Several glucose-sensing pathways have been implicated in glucose
      triggered secretion of glucagon-like peptide-1 (GLP-1) from intestinal L cells.
      One involves glucose metabolism and closure of ATP-sensitive K(+) channels, and
      another exploits the electrogenic nature of Na(+)-coupled glucose transporters
      (SGLTs). This study aimed to elucidate the role of these distinct mechanisms in
      glucose-stimulated GLP-1 secretion. METHODS: Glucose uptake into L cells (either
      GLUTag cells or cells in primary cultures, using a new transgenic mouse model
      combining proglucagon promoter-driven Cre recombinase with a ROSA26tdRFP
      reporter) was monitored with the FLII(12)Pglu-700 MUdelta6 glucose sensor.
      Effects of pharmacological and genetic interference with SGLT1 or facilitative
      glucose transport (GLUT) on intracellular glucose accumulation and metabolism
      (measured by NAD(P)H autofluorescence), cytosolic Ca(2+) (monitored with Fura2)
      and GLP-1 secretion (assayed by ELISA) were assessed. RESULTS: L cell glucose
      uptake was dominated by GLUT-mediated transport, being abolished by phloretin but
      not phloridzin. NAD(P)H autofluorescence was glucose dependent and enhanced by a
      glucokinase activator. In GLUTag cells, but not primary L cells, phloretin
      partially impaired glucose-dependent secretion, and suppressed an amplifying
      effect of glucose under depolarising high K(+) conditions. The key importance of
      SGLT1 in GLUTag and primary cells was evident from the impairment of secretion by
      phloridzin or Sglt1 knockdown and failure of glucose to trigger cytosolic Ca(2+)
      elevation in primary L cells from Sglt1 knockout mice.
      CONCLUSIONS/INTERPRETATION: SGLT1 acts as the luminal glucose sensor in L cells,
      but intracellular glucose concentrations are largely determined by GLUT activity.
      Although L cell glucose metabolism depends partially on glucokinase activity,
      this plays only a minor role in glucose-stimulated GLP-1 secretion.

PMID- 22638551
TI  - Cancer/testis antigens expression and autologous serological response in a set of
      Brazilian non-Hodgkin's lymphoma patients.
AB  - BACKGROUND: Based on their tumor-associated expression pattern, cancer/testis
      antigens (CTAs) are considered potential targets for cancer immunotherapy. We aim
      to evaluate the expression of CTAs in non-Hodgkin's lymphoma (NHL) samples and
      the ability of these patients to elicit spontaneous humoral immune response
      against CTAs. METHODS: Expression of MAGE-A family, CT7/MAGE-C1, CT10/MAGE-C2,
      GAGE and NY-ESO-1 was analyzed by immunohistochemistry in a tissue microarray
      generated from 106 NHL archival cases. The humoral response against 19 CTAs was
      tested in 97 untreated NHL serum samples using ELISA technique. RESULTS: 11.3 %
      of NHL tumor samples expressed at least 1 CTA. MAGE-A family (6.6 %), GAGE (5.7
      %) and NY-ESO-1(4.7 %) were the most frequently expressed antigens. We found no
      statistically significant correlation between CTA positivity and clinical
      parameters such as NHL histological subtype, Ann Arbor stage, international
      prognostic index score, response to treatment and overall survival. Humoral
      response against at least 1 CTA was observed in 16.5 % of NHL serum samples.
      However, overall seroreactivity was low, and strong titers (>1:1000) were
      observed in only two diffuse large B-cell lymphomas patients against CT45.
      CONCLUSION: Our findings are in agreement with most of published studies in this
      field to date and suggest an overall low expression of CTAs in NHL patients.
      However, as many new CTAs have been described recently and some of them are found
      to be highly expressed in NHL cell lines and tumor samples, further studies
      exploring the expression of different panels of CTAs are needed to evaluate their
      role as candidates for immunotherapy in NHL patients.

PMID- 22638564
TI  - Erdheim-Chester disease presenting with an intramedullary spinal cord lesion.

PMID- 22638565
TI  - A compound heterozygous missense mutation and a large deletion in the KCTD7 gene
      presenting as an opsoclonus-myoclonus ataxia-like syndrome.
AB  - Mutations in the potassium channel-related gene KCTD7 were described so far in a
      single family with progressive myoclonus epilepsy. We describe a unique
      phenotype: acute onset of myoclonus and ataxia, associated with abnormal
      opsoclonus-like eye movements; improvement of clinical symptoms under steroid
      treatment; and appearance of epileptic activity on EEG 2 years later without
      overt seizures. After excluding possible genetic causes, whole-genome exome
      sequencing was performed in order to identify the causative gene. One
      heterozygous missense mutation (R84W) was detected by exome sequencing and a
      large heterozygous deletion of exons 3 and 4 by MLPA analysis. The father is
      heterozygous for the R84W mutation and the mother is heterozygous for the exon
      3+4 deletion. The mutation affects a highly conserved segment of the predicted
      protein, changing a basic amino acid into neutral. The large deletion probably
      results in a truncated protein. The different phenotype broadens the spectrum of
      KCTD7-related diseases. Therefore, patients diagnosed as having opsoclonus
      myoclonus with an atypical course should be evaluated for KCTD7 mutations.

PMID- 22638566
TI  - Disclosing the diagnosis of multiple sclerosis: the Profile Project.
AB  - Communicating the diagnosis of multiple sclerosis (MS) is a challenging task,
      often undertaken with discomfort by most neurologists. Only a few studies have
      investigated patients' satisfaction with timing and way of receiving the
      diagnosis, but surveys regarding physicians' attitude towards diagnosis
      disclosure are even more limited. The goal of this work was to highlight Italian
      neurologists' behavioral and emotional approach to MS patients, making them
      sensitive to their difficulties and to the importance of an empathic
      relationship. The majority of Italian neurologists participating in our study
      have a good perception of their ability to manage this difficult communicating
      process and believe in the great effect this moment may have on a life-long
      disease experience. Improving communication skills may help the therapeutic
      alliance, enhancing patients' acceptance of the disease, as well as motivation
      and adherence to treatment.

PMID- 22638567
TI  - Voltage-gated potassium channel complex antibodies in Creutzfeldt-Jakob disease.

PMID- 22638568
TI  - Granulocyte colony-stimulating-factor-producing hepatocellular carcinoma with
      extensive sarcomatous changes: report of a case.
AB  - This report describes a rare case of hepatocellular carcinoma (HCC) producing
      granulocyte colony-stimulating factor (G-CSF). A 46-year-old male with chronic
      hepatitis B, who presented with fever, general malaise, loss of appetite, and
      weight loss, had a huge liver mass in the portal region. He had marked
      granulocytosis and his serum level of G-CSF was elevated. Complete tumor
      resection was performed, and the pathological assessment of the resected specimen
      revealed HCC with extensive sarcomatous changes and immunohistochemical staining
      for G-CSF and G-CSF receptor. Only a few cases of G-CSF-producing HCC have been
      reported, and this is the first case of G-CSF-producing HCC that also expressed G
      CSF receptor.

PMID- 22638570
TI  - Myh7b/miR-499 gene expression is transcriptionally regulated by MRFs and Eos.
AB  - The sarcomeric myosin gene, Myh7b, encodes an intronic microRNA, miR-499, which
      regulates cardiac and skeletal muscle biology, yet little is known about its
      transcriptional regulation. To identify the transcription factors involved in
      regulating Myh7b/miR-499 gene expression, we have mapped the transcriptional
      start sites and identified an upstream 6.2 kb region of the mouse Myh7b gene
      whose activity mimics the expression pattern of the endogenous Myh7b gene both in
      vitro and in vivo. Through promoter deletion analysis, we have mapped a distal E
      box element and a proximal Ikaros site that are essential for Myh7b promoter
      activity in muscle cells. We show that the myogenic regulatory factors, MyoD,
      Myf5 and Myogenin, bind to the E-box, while a lymphoid transcription factor,
      Ikaros 4 (Eos), binds to the Ikaros motif. Further, we show that through physical
      interaction, MyoD and Eos form an active transcriptional complex on the chromatin
      to regulate the expression of the endogenous Myh7b/miR-499 gene in muscle cells.
      We also provide the first evidence that Eos can regulate expression of additional
      myosin genes (Myosin 1 and beta-Myosin) via the miR-499/Sox6 pathway. Therefore,
      our results indicate a novel role for Eos in the regulation of the myofiber gene
      program.

PMID- 22638571
TI  - Savant Genome Browser 2: visualization and analysis for population-scale
      genomics.
AB  - High-throughput sequencing (HTS) technologies are providing an unprecedented
      capacity for data generation, and there is a corresponding need for efficient
      data exploration and analysis capabilities. Although most existing tools for HTS
      data analysis are developed for either automated (e.g. genotyping) or
      visualization (e.g. genome browsing) purposes, such tools are most powerful when
      combined. For example, integration of visualization and computation allows users
      to iteratively refine their analyses by updating computational parameters within
      the visual framework in real-time. Here we introduce the second version of the
      Savant Genome Browser, a standalone program for visual and computational analysis
      of HTS data. Savant substantially improves upon its predecessor and existing
      tools by introducing innovative visualization modes and navigation interfaces for
      several genomic datatypes, and synergizing visual and automated analyses in a way
      that is powerful yet easy even for non-expert users. We also present a number of
      plugins that were developed by the Savant Community, which demonstrate the power
      of integrating visual and automated analyses using Savant. The Savant Genome
      Browser is freely available (open source) at www.savantbrowser.com.

PMID- 22638573
TI  - DichroMatch: a website for similarity searching of circular dichroism spectra.
AB  - Circular dichroism (CD) spectroscopy is a widely used method for examining the
      structure, folding and conformational changes of proteins. A new online CD
      analysis server (DichroMatch) has been developed for identifying proteins with
      similar spectral characteristics by detecting possible structurally and
      functionally related proteins and homologues. DichroMatch includes six different
      methods for determining the spectral nearest neighbours to a query protein
      spectrum and provides metrics of how similar these spectra are and, if
      corresponding crystal structures are available for the closest matched proteins,
      information on their secondary structures and fold classifications. By default,
      DichroMatch uses all the entries in the Protein Circular Dichroism Data Bank
      (PCDDB) for its comparison set, providing the broadest range of publicly
      available protein spectra to match with the unknown protein. Alternatively, users
      can download or create their own specialized data sets, thereby enabling
      comparisons between the structures of related proteins such as wild-type versus
      mutants or homologues or a series of spectra of the same protein under different
      conditions. The DichroMatch server is freely available at
      http://dichromatch.cryst.bbk.ac.uk.

PMID- 22638572
TI  - Detection of transcriptional triggers in the dynamics of microbial growth:
      application to the respiratorily versatile bacterium Shewanella oneidensis.
AB  - The capacity of microorganisms to respond to variable external conditions
      requires a coordination of environment-sensing mechanisms and decision-making
      regulatory circuits. Here, we seek to understand the interplay between these two
      processes by combining high-throughput measurement of time-dependent mRNA
      profiles with a novel computational approach that searches for key genetic
      triggers of transcriptional changes. Our approach helped us understand the
      regulatory strategies of a respiratorily versatile bacterium with promising
      bioenergy and bioremediation applications, Shewanella oneidensis, in minimal and
      rich media. By comparing expression profiles across these two conditions, we
      unveiled components of the transcriptional program that depend mainly on the
      growth phase. Conversely, by integrating our time-dependent data with a
      previously available large compendium of static perturbation responses, we
      identified transcriptional changes that cannot be explained solely by internal
      network dynamics, but are rather triggered by specific genes acting as key
      mediators of an environment-dependent response. These transcriptional triggers
      include known and novel regulators that respond to carbon, nitrogen and oxygen
      limitation. Our analysis suggests a sequence of physiological responses,
      including a coupling between nitrogen depletion and glycogen storage, partially
      recapitulated through dynamic flux balance analysis, and experimentally confirmed
      by metabolite measurements. Our approach is broadly applicable to other systems.

PMID- 22638574
TI  - Enhanced multiplex genome engineering through co-operative oligonucleotide co
      selection.
AB  - Genome-scale engineering of living organisms requires precise and economical
      methods to efficiently modify many loci within chromosomes. One such example is
      the directed integration of chemically synthesized single-stranded
      deoxyribonucleic acid (oligonucleotides) into the chromosome of Escherichia coli
      during replication. Herein, we present a general co-selection strategy in
      multiplex genome engineering that yields highly modified cells. We demonstrate
      that disparate sites throughout the genome can be easily modified simultaneously
      by leveraging selectable markers within 500 kb of the target sites. We apply this
      technique to the modification of 80 sites in the E. coli genome.

PMID- 22638575
TI  - SAYP and Brahma are important for 'repressive' and 'transient' Pol II pausing.
AB  - Drosophila SAYP, a homologue of human PHF10/BAF45a, is a metazoan coactivator
      associated with Brahma and essential for its recruitment on the promoter. The
      role of SAYP in DHR3 activator-driven transcription of the ftz-f1 gene, a member
      of the ecdysone cascade was studied. In the repressed state of ftz-f1 in the
      presence of DHR3, the Pol II complex is pre-recruited on the promoter; Pol II
      starts transcription but is paused 1.5 kb downstream of the promoter, with SAYP
      and Brahma forming a 'nucleosomal barrier' (a region of high nucleosome density)
      ahead of paused Pol II. SAYP depletion leads to the removal of Brahma, thereby
      eliminating the nucleosomal barrier. During active transcription, Pol II pausing
      at the same point correlates with Pol II CTD Ser2 phosphorylation. SAYP is
      essential for Ser2 phosphorylation and transcription elongation. Thus, SAYP as
      part of the Brahma complex participates in both 'repressive' and 'transient' Pol
      II pausing.

PMID- 22638576
TI  - Analyzing large biological datasets with association networks.
AB  - Due to advances in high-throughput biotechnologies biological information is
      being collected in databases at an amazing rate, requiring novel computational
      approaches that process collected data into new knowledge in a timely manner. In
      this study, we propose a computational framework for discovering modular
      structure, relationships and regularities in complex data. The framework utilizes
      a semantic-preserving vocabulary to convert records of biological annotations of
      an object, such as an organism, gene, chemical or sequence, into networks (Anets)
      of the associated annotations. An association between a pair of annotations in an
      Anet is determined by the similarity of their co-occurrence pattern with all
      other annotations in the data. This feature captures associations between
      annotations that do not necessarily co-occur with each other and facilitates
      discovery of the most significant relationships in the collected data through
      clustering and visualization of the Anet. To demonstrate this approach, we
      applied the framework to the analysis of metadata from the Genomes OnLine
      Database and produced a biological map of sequenced prokaryotic organisms with
      three major clusters of metadata that represent pathogens, environmental isolates
      and plant symbionts.

PMID- 22638577
TI  - Camera: a competitive gene set test accounting for inter-gene correlation.
AB  - Competitive gene set tests are commonly used in molecular pathway analysis to
      test for enrichment of a particular gene annotation category amongst the
      differential expression results from a microarray experiment. Existing gene set
      tests that rely on gene permutation are shown here to be extremely sensitive to
      inter-gene correlation. Several data sets are analyzed to show that inter-gene
      correlation is non-ignorable even for experiments on homogeneous cell populations
      using genetically identical model organisms. A new gene set test procedure
      (CAMERA) is proposed based on the idea of estimating the inter-gene correlation
      from the data, and using it to adjust the gene set test statistic. An efficient
      procedure is developed for estimating the inter-gene correlation and
      characterizing its precision. CAMERA is shown to control the type I error rate
      correctly regardless of inter-gene correlations, yet retains excellent power for
      detecting genuine differential expression. Analysis of breast cancer data shows
      that CAMERA recovers known relationships between tumor subtypes in very
      convincing terms. CAMERA can be used to analyze specified sets or as a pathway
      analysis tool using a database of molecular signatures.

PMID- 22638578
TI  - iELM--a web server to explore short linear motif-mediated interactions.
AB  - The recent expansion in our knowledge of protein-protein interactions (PPIs) has
      allowed the annotation and prediction of hundreds of thousands of interactions.
      However, the function of many of these interactions remains elusive. The
      interactions of Eukaryotic Linear Motif (iELM) web server provides a resource for
      predicting the function and positional interface for a subset of interactions
      mediated by short linear motifs (SLiMs). The iELM prediction algorithm is based
      on the annotated SLiM classes from the Eukaryotic Linear Motif (ELM) resource and
      allows users to explore both annotated and user-generated PPI networks for SLiM
      mediated interactions. By incorporating the annotated information from the ELM
      resource, iELM provides functional details of PPIs. This can be used in proteomic
      analysis, for example, to infer whether an interaction promotes complex formation
      or degradation. Furthermore, details of the molecular interface of the SLiM
      mediated interactions are also predicted. This information is displayed in a
      fully searchable table, as well as graphically with the modular architecture of
      the participating proteins extracted from the UniProt and Phospho.ELM resources.
      A network figure is also presented to aid the interpretation of results. The iELM
      server supports single protein queries as well as large-scale proteomic
      submissions and is freely available at http://i.elm.eu.org.

PMID- 22638579
TI  - SteinerNet: a web server for integrating 'omic' data to discover hidden
      components of response pathways.
AB  - High-throughput technologies including transcriptional profiling, proteomics and
      reverse genetics screens provide detailed molecular descriptions of cellular
      responses to perturbations. However, it is difficult to integrate these diverse
      data to reconstruct biologically meaningful signaling networks. Previously, we
      have established a framework for integrating transcriptional, proteomic and
      interactome data by searching for the solution to the prize-collecting Steiner
      tree problem. Here, we present a web server, SteinerNet, to make this method
      available in a user-friendly format for a broad range of users with data from any
      species. At a minimum, a user only needs to provide a set of experimentally
      detected proteins and/or genes and the server will search for connections among
      these data from the provided interactomes for yeast, human, mouse, Drosophila
      melanogaster and Caenorhabditis elegans. More advanced users can upload their own
      interactome data as well. The server provides interactive visualization of the
      resulting optimal network and downloadable files detailing the analysis and
      results. We believe that SteinerNet will be useful for researchers who would like
      to integrate their high-throughput data for a specific condition or cellular
      response and to find biologically meaningful pathways. SteinerNet is accessible
      at http://fraenkel.mit.edu/steinernet.

PMID- 22638580
TI  - AVPpred: collection and prediction of highly effective antiviral peptides.
AB  - In the battle against viruses, antiviral peptides (AVPs) had demonstrated the
      immense potential. Presently, more than 15 peptide-based drugs are in various
      stages of clinical trials. Emerging and re-emerging viruses further emphasize the
      efforts to accelerate antiviral drug discovery efforts. Despite, huge importance
      of the field, no dedicated AVP resource is available. In the present study, we
      have collected 1245 peptides which were experimentally checked for antiviral
      activity targeting important human viruses like influenza, HIV, HCV and SARS,
      etc. After removing redundant peptides, 1056 peptides were divided into 951
      training and 105 validation data sets. We have exploited various peptides
      sequence features, i.e. motifs and alignment followed by amino acid composition
      and physicochemical properties during 5-fold cross validation using Support
      Vector Machine. Physiochemical properties-based model achieved maximum 85%
      accuracy and 0.70 Matthew's Correlation Coefficient (MCC). Performance of this
      model on the experimental validation data set showed 86% accuracy and 0.71 MCC
      which is far better than the general antimicrobial peptides prediction methods.
      Therefore, AVPpred-the first web server for predicting the highly effective AVPs
      would certainly be helpful to researchers working on peptide-based antiviral
      development. The web server is freely available at
      http://crdd.osdd.net/servers/avppred.

PMID- 22638581
TI  - Glucose depletion activates mmu-miR-466h-5p expression through oxidative stress
      and inhibition of histone deacetylation.
AB  - MicroRNAs (miRNAs) are involved in the regulation of multiple cellular processes.
      Changes of miRNA expression have been linked to the development of various
      diseases including cancer, but the molecular events leading to these changes at
      different physiological conditions are not well characterized. Here we examined
      the intracellular events responsible for the miR-466h-5p activation in mouse
      cells exposed to glucose deprivation. MiR-466h-5p is a member of the miR-297-669
      cluster located in intron 10 of Sfmbt2 gene on mouse chromosome 2 and has a pro
      apoptotic role. We showed that the time-dependant activation of miR-466h-5p, miR
      669c and the Sfmbt2 gene followed the inhibition of histone deacetylation caused
      by glucose deprivation-induced oxidative stress. This oxidative stress causes the
      accumulation of reactive oxygen species (ROS) and depletion of reduced
      glutathione (GSH) that together inhibited histone deacetylases (HDACs) activity,
      reduced protein levels of HDAC2 and increased acetylation in miR-466h-5p promoter
      region, which led to the activation of this miRNA. Based on this study and
      previous work, we suggest a possible role of miR-466h-5p (and miR 297-669
      cluster) in the cells during toxic metabolites accumulation. Improved
      characterization of the molecular events that lead to the activation of miR-466h
      5p may provide a better understanding of the relation between cellular
      environment and miRNA activation.

PMID- 22638583
TI  - Seq2Logo: a method for construction and visualization of amino acid binding
      motifs and sequence profiles including sequence weighting, pseudo counts and two
      sided representation of amino acid enrichment and depletion.
AB  - Seq2Logo is a web-based sequence logo generator. Sequence logos are a graphical
      representation of the information content stored in a multiple sequence alignment
      (MSA) and provide a compact and highly intuitive representation of the position
      specific amino acid composition of binding motifs, active sites, etc. in
      biological sequences. Accurate generation of sequence logos is often compromised
      by sequence redundancy and low number of observations. Moreover, most methods
      available for sequence logo generation focus on displaying the position-specific
      enrichment of amino acids, discarding the equally valuable information related to
      amino acid depletion. Seq2logo aims at resolving these issues allowing the user
      to include sequence weighting to correct for data redundancy, pseudo counts to
      correct for low number of observations and different logotype representations
      each capturing different aspects related to amino acid enrichment and depletion.
      Besides allowing input in the format of peptides and MSA, Seq2Logo accepts input
      as Blast sequence profiles, providing easy access for non-expert end-users to
      characterize and identify functionally conserved/variable amino acids in any
      given protein of interest. The output from the server is a sequence logo and a
      PSSM. Seq2Logo is available at http://www.cbs.dtu.dk/biotools/Seq2Logo (14 May
      2012, date last accessed).

PMID- 22638582
TI  - A role for chromatin remodellers in replication of damaged DNA.
AB  - In eukaryotic cells, replication past damaged sites in DNA is regulated by the
      ubiquitination of proliferating cell nuclear antigen (PCNA). Little is known
      about how this process is affected by chromatin structure. There are two isoforms
      of the Remodels the Structure of Chromatin (RSC) remodelling complex in yeast. We
      show that deletion of RSC2 results in a dramatic reduction in the level of PCNA
      ubiquitination after DNA-damaging treatments, whereas no such effect was observed
      after deletion of RSC1. Similarly, depletion of the BAF180 component of the
      corresponding PBAF (Polybromo BRG1 (Brahma-Related Gene 1) Associated Factor)
      complex in human cells led to a similar reduction in PCNA ubiquitination.
      Remarkably, we found that depletion of BAF180 resulted after UV-irradiation, in a
      reduction not only of ubiquitinated PCNA but also of chromatin-associated
      unmodified PCNA and Rad18 (the E3 ligase that ubiquitinates PCNA). This was
      accompanied by a modest decrease in fork progression. We propose a model to
      account for these findings that postulates an involvement of PBAF in repriming of
      replication downstream from replication forks blocked at sites of DNA damage. In
      support of this model, chromatin immunoprecipitation data show that the RSC
      complex in yeast is present in the vicinity of the replication forks, and by
      extrapolation, this is also likely to be the case for the PBAF complex in human
      cells.

PMID- 22638586
TI  - Super: a web server to rapidly screen superposable oligopeptide fragments from
      the protein data bank.
AB  - Searching for well-fitting 3D oligopeptide fragments within a large collection of
      protein structures is an important task central to many analyses involving
      protein structures. This article reports a new web server, Super, dedicated to
      the task of rapidly screening the protein data bank (PDB) to identify all
      fragments that superpose with a query under a prespecified threshold of root-mean
      square deviation (RMSD). Super relies on efficiently computing a mathematical
      bound on the commonly used structural similarity measure, RMSD of superposition.
      This allows the server to filter out a large proportion of fragments that are
      unrelated to the query; >99% of the total number of fragments in some cases. For
      a typical query, Super scans the current PDB containing over 80,500 structures
      (with ~40 million potential oligopeptide fragments to match) in under a minute.
      Super web server is freely accessible from:
      http://lcb.infotech.monash.edu.au/super.

PMID- 22638585
TI  - Cap-dependent translation without base-by-base scanning of an messenger
      ribonucleic acid.
AB  - 'Ribosome scanning' is the generally accepted mechanism for explaining how a
      ribosome finds an initiation codon located far removed from the ribosome
      recruiting site (cap structure). However, the molecular characteristics of
      ribosome scanning along 5' untranslated regions (UTRs) remain obscure. Herein,
      using a rabbit reticulocyte lysate (RRL) system and artificial ribonucleic acid
      (RNA) constructs composed of a capped leader RNA and an uncapped reporter RNA
      annealed through a double-stranded RNA (dsRNA) bridge, we show that the ribosome
      can efficiently bypass a stable, dsRNA region without melting the structure. The
      insertion of an upstream open reading frame in the capped leader RNA impaired the
      translation of reporter RNA, indicating that a ribosome associated with the 5'
      end explores the regions upstream of the dsRNA bridge in search of the initiation
      codon. These data indicate that a ribosome may skip part(s) of an messenger RNA
      5'UTR without thoroughly scanning it.

PMID- 22638584
TI  - Sequence, structure and functional diversity of PD-(D/E)XK phosphodiesterase
      superfamily.
AB  - Proteins belonging to PD-(D/E)XK phosphodiesterases constitute a functionally
      diverse superfamily with representatives involved in replication, restriction,
      DNA repair and tRNA-intron splicing. Their malfunction in humans triggers severe
      diseases, such as Fanconi anemia and Xeroderma pigmentosum. To date there have
      been several attempts to identify and classify new PD-(D/E)KK phosphodiesterases
      using remote homology detection methods. Such efforts are complicated, because
      the superfamily exhibits extreme sequence and structural divergence. Using
      advanced homology detection methods supported with superfamily-wide domain
      architecture and horizontal gene transfer analyses, we provide a comprehensive
      reclassification of proteins containing a PD-(D/E)XK domain. The PD-(D/E)XK
      phosphodiesterases span over 21,900 proteins, which can be classified into 121
      groups of various families. Eleven of them, including DUF4420, DUF3883, DUF4263,
      COG5482, COG1395, Tsp45I, HaeII, Eco47II, ScaI, HpaII and Replic_Relax, are newly
      assigned to the PD-(D/E)XK superfamily. Some groups of PD-(D/E)XK proteins are
      present in all domains of life, whereas others occur within small numbers of
      organisms. We observed multiple horizontal gene transfers even between human
      pathogenic bacteria or from Prokaryota to Eukaryota. Uncommon domain arrangements
      greatly elaborate the PD-(D/E)XK world. These include domain architectures
      suggesting regulatory roles in Eukaryotes, like stress sensing and cell-cycle
      regulation. Our results may inspire further experimental studies aimed at
      identification of exact biological functions, specific substrates and molecular
      mechanisms of reactions performed by these highly diverse proteins.

PMID- 22638587
TI  - Linear motifs confer functional diversity onto splice variants.
AB  - The pre-translational modification of messenger ribonucleic acids (mRNAs) by
      alternative promoter usage and alternative splicing is an important source of
      pleiotropy. Despite intensive efforts, our understanding of the functional
      implications of this dynamically created diversity is still incomplete. Using the
      available knowledge of interaction modules, particularly within intrinsically
      disordered regions (IDRs), we analysed the occurrences of protein modules within
      alternative exons. We find that regions removed or included by pre-translational
      variation are enriched in linear motifs suggesting that the removal or inclusion
      of exons containing these interaction modules is an important regulatory
      mechanism. In particular, we observe that PDZ-, PTB-, SH2- and WW-domain binding
      motifs are more likely to occur within alternative exons. We also determine that
      regions removed or included by alternative promoter usage are enriched in IDRs
      suggesting that protein isoform diversity is tightly coupled to the modulation of
      IDRs. This study, therefore, demonstrates that short linear motifs are key
      components for establishing protein diversity between splice variants.

PMID- 22638588
TI  - How does hydroxyl introduction influence the double helical structure: the
      stabilization of an altritol nucleic acid:ribonucleic acid duplex.
AB  - Altritol nucleic acids (ANAs) are a promising new tool in the development of
      artificial small interfering ribonucleic acids (siRNAs) for therapeutical
      applications. To mimic the siRNA:messenger RNA (mRNA) interactions, the crystal
      structure of the ANA:RNA construct a(CCGUAAUGCC-P):r(GGCAUUACGG) was determined
      to 1.96 A resolution which revealed the hybrid to form an A-type helix. As this A
      form is a major requirement in the RNAi process, this crystal structure confirms
      the potential of altritol-modified siRNAs. Moreover, in the ANA strands, a new
      type of intrastrand interactions was found between the O2' hydroxyl group of one
      residue and the sugar ring O4' atom of the next residue. These interactions were
      further investigated by quantum chemical methods. Besides hydration effects,
      these intrastrand hydrogen bonds may also contribute to the stability of ANA:RNA
      duplexes.

PMID- 22638594
TI  - Eagle's syndrome: embryology, anatomy, and clinical management.
AB  - BACKGROUND: Eagle's syndrome refers to a rare constellation of neuropathic and
      vascular occlusive symptoms caused by pathologic elongation or angulation of the
      styloid process and styloid chain. First described in 1652 by Italian surgeon
      Piertro Marchetti, the clinical syndrome was definitively outlined by Watt Eagle
      in the late 1940s and early 1950s. METHODS: This article reviews how underlying
      embryologic and anatomic pathology predicts clinical symptomatology, diagnosis,
      and ultimately treatment of the syndrome. RESULTS: The length and direction of
      the styloid process and styloid chain are highly variable. This variability leads
      to a wide range of relationships between the chain and the neurovascular elements
      of the neck, including cranial nerves 5, 7, 9, and 10 and the internal carotid
      artery. In the classic type of Eagle's syndrome, compressive cranial neuropathy
      most commonly leads to the sensation of a foreign body in the throat,
      odynophagia, and dysphagia. In the carotid type, compression over the internal
      carotid artery can cause pain in the parietal region of the skull or in the
      superior periorbital region, among other symptoms. CONCLUSIONS: Careful recording
      of the history of the present illness and review of systems is crucial to the
      diagnosis of Eagle's syndrome. After the clinical examination, the optimal
      imaging modality for styloid process pathology is spiral CT of the neck and skull
      base. Surgical interventions are considered only after noninvasive therapies have
      failed, the two most common being intraoral and external resection of the styloid
      process.

PMID- 22638595
TI  - Spinal epidural vascular tumors and malformations.

PMID- 22638596
TI  - Spinal cavernous hemangioma: a controversial terminology.

PMID- 22638597
TI  - Activation and crosstalk between the endoplasmic reticulum road and JNK pathway
      in ischemia-reperfusion brain injury.
AB  - BACKGROUND: Recent studies suggest that endoplasmic reticulum stress (ERS) is the
      key process in ischemic brain injury. The JNK pathway is also involved in the
      process of ischemic brain injury. METHOD: We established a middle cerebral artery
      occlusion/reperfusion (MCAO/R) model in rats; detected the changes in c-Jun N
      terminal kinase (JNK), GADD153 and caspase-12 at different reperfusion time
      points by immunohistochemistry, Western blot and double-label immunofluorescence;
      and observed the effect of JNK inhibitor SP600125 on the expression of JNK,
      GADD153 and caspase-12 to explore the relationship between the endoplasmic
      reticulum road and JNK pathway. RESULTS: The expression of the two hallmarks of
      ERS-GADD153 and caspase-12-significantly increased, and the activation of JNK
      also obviously increased. After interference by SP600125, the expression of p-JNk
      and caspase-12 obviously decreased, whereas the decrease of GADD153 occurred only
      after 24 h reperfusion. CONCLUSIONS: Both ERS and JNK pathways are involved in
      the pathological process of ischemic brain injury. The JNK pathway may be
      involved in the process of ERS, but perhaps has more effect on the caspase-12
      pathway.

PMID- 22638598
TI  - [Antiplatelet therapy after coronary stenting and its importance in total joint
      arthroplasty].
AB  - Coronary stenting is an effective treatment for reopening atherosclerotic
      occlusions of coronary arteries. Depending on the manifestation of coronary
      artery disease (stable CAD or acute coronary syndrome) and on the type of
      implanted stent, dual antiplatelet therapy is recommended for a period of 4 weeks
      to 12 months. In this period total joint replacement is associated with high
      blood loss and high perioperative morbidity. Therefore antiplatelet therapy is
      often discontinued and replaced by higher dosages of heparin for prophylactic
      anticoagulation. However, with this treatment regimen protection of the stent is
      doubtful and there is a high risk of stent thrombosis with myocardial infarction.
      The surgery should be scheduled after the dual antiplatelet therapy is replaced
      by lifelong aspirin therapy. On the other hand, if surgery cannot be postponed
      perioperative bridging of dual antiplatelet therapy can be conducted to minimize
      bleeding complications with the best possible stent protection. Lifelong therapy
      with aspirin should not be discontinued in any case.

PMID- 22638604
TI  - Risk of unintentional overdose with non-prescription acetaminophen products.
AB  - BACKGROUND: There is increasing concern over the risk of consumer unintentional
      misuse of non-prescription (a.k.a. 'over-the-counter') medications containing
      acetaminophen, which could lead to acute liver failure. OBJECTIVE: To determine
      the prevalence of potential misuse and overdose of over-the-counter medications
      containing acetaminophen, either alone or in combination. DESIGN: Cross
      sectional, structured interviews with literacy assessment. SETTING: One academic
      and one community-based general internal medicine practice in Chicago, IL, and
      one academic general internal medicine practice and a public hospital clinic in
      Atlanta, GA. PATIENTS: Five hundred adults seeking primary care, ages 18-80.
      MEASUREMENT: Demonstration of how and when patients would take over-the-counter
      medications containing acetaminophen, alone or in combination with one another,
      over a 24-hour period. RESULTS: Overall, 23.8 % of participants demonstrated they
      would overdose on a single over-the-counter acetaminophen product by exceeding a
      dose of four grams in a 24-hour period; 5.2 % made serious errors by dosing out
      more than six grams. In addition, 45.6 % of adults demonstrated they would
      overdose by 'double-dipping' with two acetaminophen-containing products. In
      multivariable analyses, limited literacy (Relative Risk Ratio (RR) 1.65, 95 %
      Confidence Interval (CI) 1.03-2.66) and heavy acetaminophen use in the past six
      months (RR 1.70, 95 % CI 1.10-2.64) were independently associated with overdosing
      over-the-counter products. CONCLUSION: Misunderstanding of the active ingredient
      and proper instructions for over-the-counter medications containing acetaminophen
      is common. The potential for errors and adverse events associated with
      unintentional misuse of these products is substantial, particularly among heavy
      users of acetaminophen and those with limited literacy.

PMID- 22638605
TI  - What is your understanding of your illness? A communication tool to explore
      patients' perspectives of living with advanced illness.
AB  - BACKGROUND: Provider communication courses and guidelines stress the use of open
      ended questions, such as "what is your understanding of your illness?," to
      explore patients' perceptions of their illness severity, yet descriptions of
      patients' responses are largely absent from the current literature. These
      questions are most often used by clinicians as they deliver bad news to cancer
      patients or address code status at the end of life, but have not been well
      studied in other diseases or earlier in the disease course. OBJECTIVES: To
      explore the responses of patients living with serious illness to the question
      "what is your understanding of your illness?" and to identify similarities and
      differences in themes and language used by cancer and non-cancer patients to
      discuss their illness. DESIGN: We conducted a qualitative analysis of patients'
      responses to "what is your understanding of your illness?" PARTICIPANTS: Two
      hundred nine subjects, 69 with cancer, 70 CHF, and 70 COPD, who had an estimated
      50 % 2-year survival. Mean age was 66 years. APPROACH: Responses were recorded at
      the baseline interview of a larger, longitudinal study of patients with advanced
      life-limiting illness (cancer, CHF, or COPD). After thematic content analysis
      using open coding, investigators conducted pattern analysis to examine variation
      associated with diagnosis. RESULTS: We identified five major themes: naming the
      diagnosis or describing the pathophysiology, illness history, prognosis,
      symptoms, and causality. Responses varied by diagnosis. Cancer patients'
      responses more often included specific diagnostic details and prognosis, while
      non-cancer patients referenced symptoms and causality. CONCLUSIONS: Patients'
      responses to the open-ended question "what is your understanding of your
      illness?" can provide the clinician with important information and insight on how
      they view their illness in a non-acute setting. The identified themes can serve
      as a foundation for patient-centered communication strategies as we strive to
      build a mutual understanding of illness with patients.

PMID- 22638606
TI  - Translational actomyosin research: fundamental insights and applications hand in
      hand.
AB  - This review describes the development towards actomyosin based nanodevices taking
      a starting point in pioneering studies in the 1990s based on conventional in
      vitro motility assays. References are given to parallel developments using the
      kinesin-microtubule motor system. The early developments focused on achieving
      cargo-transportation using actin filaments as cargo-loaded shuttles propelled by
      surface-adsorbed heavy meromyosin along micro- and nanofabricated channels. These
      efforts prompted extensive studies of surface-motor interactions contributing
      with new insights of general relevance in surface and colloid chemistry. As a
      result of these early efforts, a range of complex devices have now emerged,
      spanning applications in medical diagnostics, biocomputation and formation of
      complex nanostructures by self-organization. In addition to giving a
      comprehensive account of the developments towards real-world applications an
      important goal of the present review is to demonstrate important connections
      between the applied studies and fundamental biophysical studies of actomyosin and
      muscle function. Thus the manipulation of the motor proteins towards applications
      has resulted in new insights into methodological aspects of the in vitro motiliy
      assay. Other developments have advanced the understanding of the dynamic
      materials properties of actin filaments.

PMID- 22638607
TI  - The locking attachment plate for proximal fixation of periprosthetic femur
      fractures--a biomechanical comparison of two techniques.
AB  - PURPOSE: Mechanical properties of a locking attachment plate construct (LAP-LCP),
      allowing bicortical screw placement laterally to the prosthesis stem, are
      compared to a cerclage-LCP construct. METHODS: Eight right synthetic femora with
      implanted uncemented hip endoprosthesis were cut distally and fixed with LCP,
      monocortical locking screws and either LAP (n = 4) or cerclage (n = 4). Cyclic
      testing was performed with monotonically increasing sinusoidal load until
      failure. Relative movements at the plate-femur interface were registered by
      motion tracking. Statistical differences were detected by unpaired t-test and
      general linear model repeated measures. RESULTS: Stiffness of the LAP-LCP was
      significantly higher at the beginning (875.4 N/mm +/- 29.8) and after 5000 cycles
      (1213.0 N/mm +/- 101.1) compared to the cerclage-LCP (644.96 N/mm +/- 50.1 and
      851.9 N/mm +/- 81.9), with p = 0.013. Relative movements for AP-bending (B) and
      axial translation (T) of the LAP-LCP at the beginning (0.07 degrees  +/- 0.02,
      0.20 mm +/- 0.08), after 500 cycles (0.16 degrees  +/- 0.10, 0.26 mm +/- 0.07)
      and after 5000 cycles (0.26 degrees  +/- 0.11, 0.31 mm +/- 0.07) differed
      significantly from the cerclage-LCP (beg.: 0.26 degrees  +/- 0.04, 0.28 mm +/-
      0.05; 500 cyc: 0.47 degrees  +/- 0.03, 0.53 mm +/- 0.07; 5000 cyc.: 0.63 degrees 
      +/- 0.18, 0.79 mm +/- 0.13), with B: p = 0.02, T: p = 0.04. Relative movements
      for medial bending were not significantly different between the two constructs.
      Cycles to failure (criterion 1 mm axial translation) differed significantly
      between LAP-LCP (19,519 +/- 1,758) and cerclage-LCP (11,265 +/- 2,472), with p =
      0.035. CONCLUSIONS: Biomechanically, the LAP-LCP construct improves proximal
      fixation of periprosthetic fractures compared to the cerclage-LCP construct.

PMID- 22638608
TI  - Sagittal placement of the femoral component in total knee arthroplasty predicts
      knee flexion contracture at one-year follow-up.
AB  - PURPOSE: Flexion contracture has been shown to impair function and reduce
      satisfaction following total knee arthroplasty (TKA). The aim of this study was
      to identify modifiable intra-operative variables that predict post-TKA knee
      extension. METHODS: Data was collected prospectively on 95 patients undergoing
      total knee arthroplasty, including pre-operative assessment, intra-operative
      computer assisted surgery (CAS) measurements and functional outcome including
      range of motion at one year. Patients were divided into two groups: those with
      mild flexion contracture (> 5 degrees ) at the one-year follow-up and those
      achieving full extension. RESULTS: The sagittal orientation of the distal femoral
      cut differed significantly between groups at the one-year follow-up (p = 0.014).
      Sagittal alignment of greater than 3.5 degrees  from the mechanical axis was
      shown to increase the relative risk of a mild flexion contracture at one-year
      follow-up by 2.9 times, independent of other variables. CONCLUSION: Increasing
      the sagittal alignment of the distal femoral cut more than 3.5 degrees  from the
      mechanical axis is an independent risk factor for clinically detectable flexion
      contracture one year from index procedure.

PMID- 22638611
TI  - Estrogen synthesis genes CYP19A1, HSD3B1, and HSD3B2 in hypertensive disorders of
      pregnancy.
AB  - Hypertension in pregnancy is a multifactorial disorder caused by a complex
      combination of environmental factors and several predisposing genes. Since
      estrogen modulates placental vascular development, estrogen synthases are
      considered plausible candidate genes. The aim of this haplotype-based case
      control study was to estimate whether polymorphisms of the maternal estrogen
      synthesis genes (CYP19A1, HSD3B1 and HSD3B2) are associated with preeclampsia
      (PE) and gestational hypertension (GH). To examine the genetic markers in 69 PE
      and 62 GH patients and in 155 age-matched, primiparous, healthy control subjects,
      genotyping of 5 SNPs for the CYP19A1 gene (rs1870049, rs936306, rs700518,
      rs700519, and rs4646), 3 SNPs for the HSD3B1 gene (rs3765945, rs6203, and
      rs1047303), and 2 SNPs for the HSD3B2 gene (rs2854964 and rs1819698) was
      performed. For rs700158 of CYP19A1, the frequencies of the AG+GG genotype and the
      G allele were significantly higher in PE as compared to controls (P = 0.037, P =
      0.033, respectively). Logistic regression analyses indicated that the AG+GG
      genotype of rs700158 was a PE risk factor (odds ratio = 2.15, P = 0.026). In
      addition, the frequency of the G-G haplotype established by rs700518-rs4646 was
      also significantly higher for PE (P = 0.017). These data suggest that the
      estrogen synthesis gene, CYP19A1 is associated with PE in the Japanese
      population.

PMID- 22638612
TI  - Genotype-phenotype correlation in juvenile Paget disease: role of molecular
      alterations of the TNFRSF11B gene.
AB  - Juvenile Paget disease (JPD) {MIM 239000} is a rare inherited bone disease that
      affects children. The patients affected with JPD present an altered bone
      turnover, therefore, show a phenotype characterized by progressive bone
      deformities, fractures, and short stature. Deletions or missense mutations of the
      TNFRSN11B gene are common in these children. This gene encodes a soluble protein,
      the osteoprotegerin, which leads to uncontrolled osteoclastogenesis when mutated.
      JPD is characterized by a strong genotype-phenotype correlation, so depending on
      the alteration of the TNFRSN11B gene, the phenotype is variable. This review
      describes the different clinical features which are characteristic of JPD and the
      correspondence with the different molecular alterations of the TNFRSN11B gene.

PMID- 22638617
TI  - Six-month visual prognosis in eyes with submacular hemorrhage secondary to age
      related macular degeneration or polypoidal choroidal vasculopathy.
AB  - BACKGROUND: To determine clinical or imaging prognostic features for visual
      outcome in eyes with submacular hemorrhage secondary to age-related macular
      degeneration (AMD) or polypoidal choroidal vasculopathy (PCV). METHODS: A
      prospective case series of 11 eyes from 11 patients with submacular hemorrhage
      secondary to AMD or PCV. All participants had measurement of clinical
      characteristics, fundus angiogram, and indocyanine green angiography, spectral
      domain optical coherence tomography (OCT, Cirrus, Zeiss) at baseline and 6
      months. RESULTS: Median visual acuity improved from 20/132 to 20/63 at month 6.
      The median improvement in vision was 0.20 LogMAR units. Proportion of eyes with
      best-corrected visual acuity (BCVA) >= 1.0 increased from 6/11 (54.5 %) at
      baseline to 8/11 (72.7 %) at month 6. Eyes with BCVA > 1.0 were more likely to
      have larger area of hemorrhage and thinner subfoveal neurosensory retinal
      thickness at baseline and at month 6. CONCLUSIONS: Thinner neurosensory retina
      demonstrated on OCT at baseline may be a useful prognostic sign for limited
      visual recovery.

PMID- 22638618
TI  - Interpersonal and affective dimensions of psychopathic traits in adolescents:
      development and validation of a self-report instrument.
AB  - We report the development and psychometric evaluations of a self-report
      instrument designed to screen for psychopathic traits among mainstream community
      adolescents. Tests of item functioning were initially conducted with 26
      adolescents. In a second study the new instrument was administered to 150 high
      school adolescents, 73 of who had school records of suspension for antisocial
      behavior. Exploratory factor analysis yielded a 4-factor structure (Impulsivity
      alpha = 0.73, Self-Centredness alpha = 0.70, Callous-Unemotional alpha = 0.69,
      and Manipulativeness alpha = 0.83). In a third study involving 328 high school
      adolescents, 130 with records of suspension for antisocial behavior, competing
      measurement models were evaluated using confirmatory factor analysis. The
      superiority of a measurement model represented by four correlated factors was
      supported, and this model was invariant across gender and age. The findings
      provide researchers and clinicians with a psychometrically strong, self-report
      instrument and a greater understanding of psychopathic traits in mainstream
      adolescents.

PMID- 22638623
TI  - Clinical usefulness of KRAS, BRAF, and PIK3CA mutations as predictive markers of
      cetuximab efficacy in irinotecan- and oxaliplatin-refractory Japanese patients
      with metastatic colorectal cancer.
AB  - BACKGROUND: Anti-epidermal growth factor receptor (EGFR) antibodies, cetuximab,
      and panitumumab are established as a new treatment option for metastatic
      colorectal cancer (mCRC). Among activating mutations downstream of EGFR, the KRAS
      mutation, which is present in 30-45 % of CRC patients, has shown to be a
      predictive biomarker of resistance to anti-EGFR antibody therapy based on
      Caucasian studies. METHODS: Forty-three chemotherapy-refractory Japanese patients
      with mCRC were treated with cetuximab monotherapy or cetuximab plus irinotecan.
      KRAS, BRAF, and PIK3CA mutational status of tumors was assessed. The association
      between mutational status and treatment outcome was evaluated. RESULTS: Of 43
      tumors, KRAS, BRAF, and PIK3CA mutations were identified in 12 (27.9 %), 2 (4.7
      %), and 2 (4.7 %) tumors, respectively. The wild-type KRAS subgroup showed better
      clinical outcomes than the mutant KRAS subgroup in terms of response rate (RR)
      (31.3 % vs. 0 %, P = 0.034) and progression-free survival (PFS) (5.1 vs. 3.0
      months, P = 0.017). No responder to treatment was shown in 16 (37.2 %) patients
      with tumors harboring mutations in any one of the three genes (KRAS, BRAF, and
      PIK3CA). The wild-type subgroup without any mutations in KRAS, BRAF, and PIK3CA
      had a better RR (37.0 %) and PFS (6.4 months) than did the wild-type KRAS
      subgroup. CONCLUSION: Our data indicated that KRAS status is predictive of
      cetuximab response in the Japanese population. The additional analysis of BRAF
      and PIK3CA genes in wild-type KRAS patients could improve selection of patients
      who are most likely to benefit from anti-EGFR antibody therapy.

PMID- 22638624
TI  - Concomitant polypharmacy is associated with irinotecan-related adverse drug
      reactions in patients with cancer.
AB  - BACKGROUND: Patients with cancer often receive chemotherapeutic agents
      concurrently with other medications to treat comorbidity. The practical effects
      of concomitant medications, especially polypharmacy, on adverse drug reactions
      related to irinotecan-based chemotherapy are not well documented. METHODS:
      Associations of adverse drug reactions related to irinotecan monotherapy or a
      combination of irinotecan, 5-fluorouracil, and L-leucovorin (FOLFIRI) with
      concomitant medicines used to treat comorbidity were retrospectively investigated
      in Japanese patients with cancer. RESULTS: Of the 172 patients, 118 received
      concomitant medications. Twenty-one patients had grade 4 neutropenia and/or grade
      3 or 4 diarrhea. Univariate and multivariate analyses revealed that concomitant
      medications were significantly associated with irinotecan-related severe
      neutropenia and/or diarrhea (P = 0.023 and 0.044). Multiple concomitant
      medications were significantly related to severe irinotecan-related toxicity in
      patients given monotherapy or FOLFIRI (P = 0.01). The incidence of severe
      irinotecan-related toxicities increased in parallel with the number of
      concomitant medications. CONCLUSION: We found that multiple concomitant medicines
      were significantly associated with severe irinotecan-related toxicity, indicating
      that polypharmacy must be effectively managed to decrease the risk of adverse
      drug reactions in patients with cancer who received irinotecan-based
      chemotherapy.

PMID- 22638637
TI  - An uncommon cause of cemented unicompartmental knee arthroplasty failure:
      fracture of metallic components.
AB  - PURPOSE: Despite good overall clinical results, unicompartmental knee
      replacements (UKR) are not without their problems and failures have been
      reported. The most common causes of UKR failure are component loosening, poor
      patient selection, poor surgical technique, polyethylene wear and progression of
      arthritis in other compartments. The purpose of this study is to present a series
      of atraumatic fractures of metallic components in a UKR treated in a single
      orthopaedic centre. METHOD: Since 1999, 121 failed unicompartmental knee
      arthroplasties have been referred to our centre. In six of these, atraumatic
      breakage of a metal component in the cemented UKR was seen and included in this
      study. Pre-operative alignment, BMI and implant longevity were documented. The
      femoral implant failed in 4 patients and the tibial implant in a further 2.
      RESULTS: All the femoral implant fractures occurred within 3 years of UKR surgery
      (mean: 22.2 months, SD: 10.6 months). Tibial implant breakage occurred at a mean
      of 8.5 years (SD: 2.4 months) following UKR. All patients were treated with
      conversion to a navigated total knee replacement. A primary total knee
      arthroplasty was used in all cases with one patient requiring a tibial component
      incorporating a wedge and stem following breakage of the original UKR tibial
      implant. CONCLUSION: Fracture of the metallic components is a potential cause of
      failure of unicompartmental knee arthroplasty. In our experience, the incidence
      of this complication was 4.9 % of all UKR failures. Patients with a BMI greater
      than 30 and a progressive deterioration in limb alignment were at greater risk.

PMID- 22638638
TI  - Medial patellofemoral ligament reconstruction with lateral soft tissue release in
      adult patients with habitual patellar dislocation.
AB  - PURPOSE: Habitual dislocation of the patella is a rare condition and a treatment
      plan has not yet been established. The purpose of this case report is to assess
      the effectiveness of medial patellofemoral ligament (MPFL) reconstruction for
      treating adults with habitual dislocation. METHODS: We performed MFPL
      reconstruction in two women with habitual patellar dislocation. Patient 1 was 39
      and Patient 2 was 57 years old. Both patients frequently experienced giving way
      and received surgical treatments that involved extensive release of tight lateral
      soft tissue followed by medial patellofemoral ligament reconstruction using
      semitendinosus tendon. RESULTS: Follow-ups at 5 years (Patient 1) and 3 years
      (Patient 2) after operation confirmed no recurrent dislocation in either patient
      and significantly improved knee function. CONCLUSIONS: Although a longer-term
      follow-up is necessary, MPFL reconstruction combined with lateral soft tissue
      release seems a promising treatment for habitual dislocation of the patella in
      adults. LEVEL OF EVIDENCE: V.

PMID- 22638639
TI  - Molecular characterisation of beak and feather disease virus (BFDV) in New
      Zealand and its implications for managing an infectious disease.
AB  - Beak and feather disease virus (BFDV) infections are often fatal to both captive
      and wild parrot populations. Its recent discovery in a wild population of native
      red-fronted parakeets has raised concerns for the conservation of native parrots,
      all of which are threatened or endangered. The question of a recent introduction
      versus a native genotype of the virus poses different conservation-management
      challenges, and thus, a clear understanding of the molecular phylogeny of BDFV is
      a crucial step towards integrated management planning. This study represents the
      first comprehensive attempt to screen New Zealand's endangered and threatened
      psittacines systematically for BFDV. We sampled and screened kakapos (Strigops
      habroptilus), kakas (Nestor meridionalis), keas (N. notabilis), Chatham parakeets
      (Cyanoramphus forbesi), Malherbe's parakeets (Cyanoramphus malherbi), yellow
      crowned parakeets (C. auriceps) and red-fronted parakeets (Cyanoramphus
      novaezelandiae), as well as eastern rosellas (Platycercus eximius), an introduced
      species that is now common throughout the North Island, for BFDV. Out of all
      species and populations sampled (786 individuals), we found 16 BFDV-positive red
      fronted parakeets from Little Barrier Island/Hauturu, seven eastern rosellas from
      the Auckland region, and eight yellow-crowned parakeets from the Eglinton Valley
      in the South Island. The full genomes of the viral isolates from the red-fronted
      parakeets share 95-97 % sequence identity to those from the invasive eastern
      rosellas and 92.7-93.4 % to those isolates from the South Island yellow-crowned
      parakeets. The yellow-crowned parakeet BFDV isolates share 92-94 % sequence
      identity with those from eastern rosellas. The low level of diversity among all
      BFDV isolates from red-fronted parakeets could suggest a more recent infection
      among these birds compared to the yellow-crowned parakeets, whereas the diversity
      in the eastern rosellas indicates a much more established infection. Pro-active
      screening and monitoring of BFDV infection rates in aviaries as well as in wild
      populations are necessary to limit the risk of transmission among threatened and
      endangered parrot populations in New Zealand.

PMID- 22638644
TI  - Sickness absence due to mental health disorders--a societal perspective.
AB  - BACKGROUND: Sickness absence (SA) is affected by societal factors. Increasing
      socioeconomic stress may cause or worsen mental health disorders, which are among
      the most frequent causes of SA. Employees may also be more cautious about being
      absent, for example in times of poor economy. AIMS: To monitor the incidence of
      SA due to mental health disorders in the Netherlands from 2001 to 2010. METHODS:
      Descriptive observational study of long-term (> 3 weeks) SA available from an
      occupational health service register. The incidence of both total and mental
      health long-term SA in each year was calculated and evaluated alongside the
      changes in SA compensation policies, gross national product and national
      unemployment statistics. The incidence of mental health SA was stratified based
      on the economic (agricultural, industrial, private, public) sector. RESULTS: The
      incidence of both total and mental health SA decreased gradually since 2004, and
      fell during the economic recession in 2009 in all economic sectors, particularly
      the agricultural and industrial sectors. The incidence of mental health SA
      increased with preliminary economic recovery in 2010 in the private and public
      sectors, but not in the agricultural and industrial sectors. CONCLUSIONS: Long
      term SA due to mental health disorders has decreased since 2004, but further
      studies across countries are required to confirm and explain this trend.

PMID- 22638645
TI  - Probable occupational pneumonitis caused by inhalation of crushed clozapine.
AB  - We present a case of non-specific interstitial pneumonia (NSIP) probably caused
      by exposure to  inhaled clozapine powder. The patient worked in a pharmacy and
      crushed clozapine tablets over  several years. She presented with insidious onset
      of breathlessness and had mild hypoxia.  High-resolution computed tomography
      demonstrated centrilobular nodules with peribronchial  consolidation. Lung biopsy
      revealed a mixed cellular and fibrotic NSIP. Her symptoms and  radiological 
      findings  resolved once exposure to clozapine powder ceased. The clear temporal
      relationship  between increased  exposure to inhaled clozapine and the
      development of NSIP, followed by the  subsequent resolution on cessation of
      exposure, strongly suggest an occupational cause. Both the active ingredients and
      the excipients of powdered medicine may be responsible for causing  pneumonitis
      in chronic exposure.

PMID- 22638647
TI  - Decreased response to cAMP in the glucose and glycogen catabolism in perfused
      livers of Walker-256 tumor-bearing rats.
AB  - The hepatic response to cyclic adenosine monophosphate (cAMP) and N6-monobutyryl
      cAMP (N6-MB-cAMP) in the glucose and glycogen catabolism and hepatic glycogen
      levels were evaluated in Walker-256 tumor-bearing rats, on days 5 (WK5), 8 (WK8),
      and 11 (WK11) after the implantation of tumor. Rats without tumor fed ad libitum
      (fed control rats) or that received the same daily amount of food ingested by
      anorexics tumor-bearing rats (pair-fed control rats) or 24 h fasted (fasted
      control rats) were used as controls. Glucose and glycogen catabolism were
      measured in perfused liver. Hepatic glycogen levels were lower (p < 0.05) in WK5,
      WK8, and WK11 rats in comparison with fed control rats, but not in relation to
      the pair-fed control rats. However, the stimulatory effect of cAMP (3 and 9 MUM)
      in the glycogen catabolism was lower (p < 0.05), respectively, in WK5 and WK8
      rats compared to the pair-fed and fed control rats. Accordingly, the suppressive
      effect of cAMP (6 MUM) in the glucose catabolism, under condition of depletion of
      hepatic glycogen (24 h fast), was lower (p < 0.05) in WK5 and WK11 rats than in
      fasted control rats. Similarly, the suppressive effect of N6-MB-cAMP (1 MUM), a
      synthetic analogue of cAMP that it is not degraded by phosphodiesterase 3B
      (PDE3B), in the glucose catabolism was lower (p < 0.05) in WK5 rats compared to
      fasted control rats. In conclusion, livers of Walker-256 tumor-bearing rats
      showed lower response to cAMP in the glucose and glycogen catabolism in various
      stages of tumor development (days 5, 8 and 11), which was probably not due to the
      lower hepatic glycogen levels nor due to the increased activity of PDE3B.

PMID- 22638648
TI  - Early cardiovascular changes occurring in diet-induced, obese insulin-resistant
      rats.
AB  - The metabolic syndrome is recognized as a cluster of disturbances associated with
      obesity, type 2 diabetes and hypertension. Over the past two decades, the number
      of people with the metabolic syndrome has increased at an alarming rate. This
      increase is associated with the global epidemic of both obesity and diabetes.
      Cardiovascular mortality is increased among diabetics and obesity-related insulin
      resistant patients, and obesity is currently recognized as independent risk
      factor for cardiovascular disease. We aimed to establish the effects of a short
      period of an altered diet on the heart using a rat model of hyperphagia-induced
      obesity (diet supplemented with sucrose and condensed milk for 8 weeks = DIO)
      compared to age-matched controls. Isolated, perfused hearts were subjected to
      global or regional ischaemia/reperfusion. Function on reperfusion was recorded
      and infarct size determined. A plasma lipid profile was established via HPLC
      based methods and proteins involved in metabolic signalling determined either by
      western blotting or RT-PCR. 8 weeks of diet resulted in whole-body but not
      myocardial insulin resistance, increased plasma triglyceride and phospholipid
      levels as well as increased lipid peroxidation. Despite the similar baseline
      function, hearts from DIO animals showed significantly poorer postischaemic
      recovery than controls (41.9 % RPP recovery vs 57.9 %, P < 0.05, n = 7-11/group)
      but surprisingly, smaller infarct size (24.95 +/- 1.97 vs 47.26 +/- 4.05 % of the
      area at risk, P < 0.005, n = 8/group). Basal phosphorylation of PKB/Akt was
      elevated but IRS-1 and SERCA-2 expression severely downregulated. In conclusion,
      after only 8 weeks of a slight change in diet, the rat heart shows signs of
      metabolic remodelling. Some of these changes may be protective but others may be
      detrimental and eventually lead to maladaptation.

PMID- 22638651
TI  - Homeowner attitudes and practices towards residential landscape management in
      Ohio, USA.
AB  - This study describes the results of a survey of 432 homeowners in Ohio, USA
      concerning their perceptions and practices regarding management of residential
      landscapes. The results reveal that outdoor residential environments are
      extremely important to homeowners, who tend to view their yards as serving
      multiple functions: a place to observe nature and to socialize as well as a place
      of beauty and recreation. Use of a lawn care company to apply chemicals is
      reported by 22 % of respondents, while 40 % either apply chemicals themselves or
      have someone other than a lawn care company do it. Logistic regressions reveal
      that factors influencing a homeowner's decision to employ a lawn care company or
      to apply chemicals themselves include: household income (+), perceived impacts on
      the environment (-), whether the next door neighbor does it (+), and type of
      residential environment (rural -, suburban and urban +). A theme that emerges
      throughout the study is the perceived importance of the role of the lawn in
      residents' sense of social status or acceptance in the neighborhood. This
      perception can be viewed as a positive in ensuring that residential environments
      are well maintained, but also as a negative resulting in environmental
      degradation or presenting a barrier to creativity in the development of
      alternative residential environments. Specific policy implications of these
      findings are that efforts aimed at educating homeowners about the environmental
      impacts of their lawn care choices are likely to have more success if they are
      directed at neighborhood groups rather than individuals, show that alternatives
      are easy to adopt, affordable, and can produce the characteristics of lawns that
      homeowners seek.

PMID- 22638653
TI  - Unusual type of growth hormone-producing pituitary tumor in acromegaly.

PMID- 22638652
TI  - Gender effects on the coordination of subdivisions of the trapezius muscle during
      a repetitive box-folding task.
AB  - This study aimed at investigating gender difference in the coordination of the
      subdivisions of the trapezius muscle during a repetitive box-folding movement
      task. Twenty-two healthy volunteers (11 males and 11 females) performed the
      repetitive box-folding task for 34 min. During the task, perceived exertion and
      surface electromyographic (EMG) signals from the upper, middle, and lower
      trapezius subdivisions were recorded. Absolute and normalised root mean square
      (RMS) values as well as normalised mutual information (NMI) values were
      calculated to assess, respectively, activation levels within muscle subdivisions
      and functional connectivity among subdivisions. Females compared with males were
      characterised by higher normalised RMS values in the upper trapezius (P < 0.05)
      and higher NMI values within the upper-middle subdivision pair (P < 0.05) during
      repetitive box-folding. The elevated normalised level of activation of the upper
      trapezius as well as the enhanced functional connectivity among upper-middle
      trapezius subdivisions underlined that females adopted a different motor strategy
      than males did during a dynamic repetitive task. Such differences within and
      among muscle subdivisions may not be a favourable trait and could partly
      contribute to the higher prevalence of musculoskeletal disorders reported in
      females.

PMID- 22638654
TI  - Water-clear parathyroid adenoma: report of two cases and literature review.

PMID- 22638655
TI  - Carney Stratakis syndrome in a patient with SDHD mutation.

PMID- 22638666
TI  - Differential profile analysis of urinary cytokines in patients with overactive
      bladder: comment.

PMID- 22638656
TI  - Over-expression of integrin-linked kinase correlates with aberrant expression of
      Snail, E-cadherin and N-cadherin in oral squamous cell carcinoma: implications in
      tumor progression and metastasis.
AB  - Integrin-linked kinase (ILK), an intracellular protein with serine/threonine
      protein kinase activities, plays a key role in integrin mediated cell-excellular
      matrix interactions, regulating cell proliferation, apoptosis, differentiation,
      and migration. ILK has been implicated in the development and progression in
      several malignancies. However, the role of ILK and ILK-mediated epithelial
      mensenchymal transition (EMT) in the progression of oral squamous cell carcinoma
      (OSCC) has not been well understood. Here, by immunohistochemistry, we studied
      the expression of ILK, Snail, E-cadherin and N-cadherin in 98 primary OSCC
      specimens and analyzed their correlations with clinicopathologic profiles and
      clinical outcome. We also investigated the expression of ILK in 42 corresponding
      lymph node metastases. Positive expression of ILK protein was detected in 87.8 %
      of the primary tumors and 100 % of metastatic lesions. Increased ILK expression
      was correlated strongly with enhanced tumor invasion, higher tumor grade,
      advanced clinical stage, positive lymph node status and increased risk of
      recurrence. Higher ILK expression was also observed in lymph node metastases in
      comparison with the corresponding primary tumor. Moreover, up-regulation of Snail
      and N-cadherin and down-regulation of E-cadherin correlated significantly with
      both ILK over-expression and tumor invasion. Patients with higher ILK expression
      exhibited shorter disease-free survival while those with absent E-cadherin
      expression exhibited shorter overall and disease-free survival. Taken together,
      our results suggest that ILK may have an important role in progression and
      metastasis of OSCC, possibly through EMT involving up-regulation of Snail and
      consequent aberrant expression of E-cadherin and N-cadherin. ILK should be
      considered as a critical prognostic indicator for patients with OSCC.

PMID- 22638668
TI  - Robot-assisted surgery:--impact on gynaecological and pelvic floor reconstructive
      surgery.
AB  - The da Vinci Surgical System dominates robotic surgery, as the only robotic
      device to have FDA approval in gynaecology. The benefits of robot-assisted
      surgery include decreased length of stay, decreased blood loss and analgesic
      requirements. Ergonomic improvements allow the surgeon to operate with less risk
      of neck and back injury. Unfortunately the initial economic impact of purchasing
      and maintaining a robot are great but must be balanced with the potential savings
      from reduced length of stay and earlier return to normal activity. This review
      looks at the uses for the robot in both gynaecology and urogynaecology, assessing
      the efficacy of this modality compared to both straight stick (laparoscopy) and
      open procedures. We assess the benefits to both patient and surgeon from the
      available literature. Within the current economic environment we appraise the
      costs associated with the robot.

PMID- 22638669
TI  - Urethral prolapse in premenopausal, healthy adult woman.
AB  - Urethral prolapse is an uncommon clinical condition that is reported
      predominantly in children and postmenopausal women. We describe a case of a 39
      year-old woman who presented at the emergency room with vaginal bleeding and pain
      related to Valsalva maneuver (lifting weight). She described several similar
      previous episodes, which started during her second pregnancy at 32 years of age.
      The episodes initially occurred every 6 months, but she did not seek medical
      assistance for 7 years, during which time symptoms became more frequent. She had
      no previous history of irradiation, pelvic infection, or urogenital surgery.
      During physical examination, a urethral prolapse was identified. Pelvic and
      urinary ultrasound (US) showed no other abnormality. The patient underwent
      cystourethroscopy and surgical excision of the urethral prolapse, with complete
      resolution of symptoms. Histopathology confirmed benign inflammatory urethral
      mucosa tissue with edema and vascular congestion.

PMID- 22638674
TI  - Prehabilitation to enhance postoperative recovery for an octogenarian following
      robotic-assisted hysterectomy with endometrial cancer.
AB  - PURPOSE: Postoperative complications represent a major concern for elderly
      patients. We report a case of a medically complex and frail 88-yr-old woman with
      endometrial cancer who was scheduled for a robotic-assisted total abdominal
      hysterectomy. In addition to her cardiac morbidity she presented with several
      risk factors for neurocognitive decline, including prior episodes of
      postoperative delirium. CLINICAL FEATURES: The patient underwent functional,
      nutritional, and neuropsychological assessments prior to a three-week
      prehabilitation home-based program consisting of strength and endurance exercises
      as well as nutritional optimization. Remarkably, there were no episodes of
      postoperative confusion, and over the following eight weeks, she continued to
      show sustained improvement in exercise tolerance (as per the six-minute walk
      test), cognitive function (as per the Repeatable Battery for the Assessment of
      Neuropsychological Status), and overall functional capacity (Short Form-36).
      CONCLUSION: This report provides suggestive evidence that a prehabilitation
      program optimized the health of this elderly patient and may have prevented a
      further episode of postoperative delirium. Prehabilitation protocols should be
      evaluated in clinical trials to evaluate their efficacy and the target
      populations who may benefit and to elucidate the underlying mechanisms
      responsible for enhanced recovery in the perioperative setting.

PMID- 22638675
TI  - Chemotherapy within 30 days before surgery does not augment postoperative
      mortality and morbidity.
AB  - BACKGROUND: Preoperative chemotherapy is frequently given to shrink or decrease
      the chance of metastasis. However, chemotherapy has well-recognized side effects
      that may complicate the perioperative period. We therefore tested the hypotheses
      that chemotherapy within 30 days before cancer surgery is associated with an
      increased risk of mortality and with a composite of major morbidities within 30
      postoperative days. METHODS: We evaluated 971,455 patients from the American
      College of Surgeons National Surgical Quality Improvement Program database.
      Patients were defined as having chemotherapy when they were given any
      chemotherapy for malignancy within 30 days before surgery. We successfully
      matched 1,348 pairs of chemotherapy recipients and non-recipients. RESULTS:
      Twenty-one of the 1,348 (1.6%) non-chemotherapy patients died within 30 days
      after surgery compared with 30 of the 1,348 (2.2%) chemotherapy patients. The
      odds of mortality were not statistically different between groups based on our
      logistic regression model [odds ratio (OR) = 1.47; 95% confidence interval (CI)
      0.82 to 2.64; P = 0.19]. The most common complication observed was wound
      infection in 13.1% of non-chemotherapy patients compared with 14.2% of the
      chemotherapy patients. There was similarly no difference between groups for the
      collapsed composite of major morbidities [OR = 1.17; 95% CI 0.97 to 1.42; P =
      0.09]. CONCLUSION: Preoperative use of neoadjuvant chemotherapy in cancer
      patients undergoing resection surgeries was not associated with a higher rate of
      early postoperative complications or mortality.

PMID- 22638676
TI  - A brief review of practical preoperative cognitive screening tools.
AB  - PURPOSE: Preoperative cognitive impairment is associated with the development of
      postoperative delirium, a common and consequential complication of major surgery
      in older patients. Screening for cognitive impairment should become a routine
      part of the preoperative evaluation of older patients; however, its
      implementation is hampered by limited clinical time and resources. The objective
      of this review was to identify cognitive screening tools that could be easily
      incorporated into the evaluation of older patients before major surgery. SEARCH
      STRATEGY: Using strict inclusion and exclusion criteria, we searched PubMed over
      a 15-year period for short and simple cognitive screening tools. In addition, we
      reviewed studies that examined these cognitive screening tools in a perioperative
      environment. SEARCH RESULTS: We identified six cognitive screening tools that
      could each be administered in 2.5 min or less. Among the tools, sensitivity for
      cognitive impairment ranged from 79-99%, while specificity ranged from 70-98%.
      Only one (Mini-Cog) of the six tools we identified had been tested in a
      perioperative environment. CONCLUSIONS: Incorporating a cognitive screening
      assessment into the preoperative evaluation of older patients is feasible. More
      research is needed to validate cognitive screening tools in the perioperative
      setting.

PMID- 22638680
TI  - Laparoscopic gastric bypass for the adolescent patient: long-term results.
AB  - BACKGROUND: Obesity is a major public health problem in the developed world. The
      National Survey of Children's Health 2003 estimated around 17 million children in
      the USA to be overweight, making this a significantly alarming disease in the
      young population. Findings from the Third National Health and Nutrition
      Examination Survey demonstrated at least 30 % of overweight adolescents to be
      suffering from the metabolic syndrome. Combined metabolic and restrictive
      bariatric operations have been shown to improve or resolve these various
      comorbidities, and surgical therapy is recommended as a part of a
      multidisciplinary approach to the treatment of morbid obesity in adults. Data in
      the adolescent population are sparse. METHODS: This is a retrospective,
      descriptive study of prospectively collected data over 10 years. Twenty-five
      adolescents between the ages of 14 and 18 years underwent laparoscopic Roux-en-Y
      gastric bypass (RYGBP) using a standard technique by a single surgeon with follow
      up of at least 5 years. RESULTS: Twenty of the 25 patients were available for
      follow-up from 5 to 10 years after their operation. Average BMI preop/postop was
      45.7/28.6 kg/m(2). Average percentage of excess body weight loss was 77.7 %.
      Average BMI change was 17.1. CONCLUSION: Our long-term data demonstrate that
      laparoscopic RYGBP is a safe and effective operation for morbidly obese
      adolescents, in the proper setting. We advocate that surgical intervention be
      recommended for this population using the same NIH guidelines used for adults.

PMID- 22638681
TI  - Conjugated bile acids associate with altered rates of glucose and lipid oxidation
      after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (RYGB) induces a more favorable
      metabolic profile than expected by weight loss alone. In this study, we
      investigated the effect of RYGB on serum bile acid levels and their relation to
      clinical outcomes. METHODS: We included 30 obese patients who underwent RYGB (BMI
      = 46.1 +/- 5.9 kg/m(2)). Clinical measurements and laboratory determinations were
      performed before surgery and 1 year after surgery. Fasting serum bile acids were
      measured by an enzymatic method and individual bile acids were quantified by HLPC
      tandem mass spectrometry. Indirect calorimetry was performed to measure the rates
      of energy expenditure and substrate oxidation. RESULTS: Fasting total serum bile
      acid levels increased twofold after RYGB (pre, 3.68 +/- 2.03 vs. post, 7.06 +/-
      9.65 MUmol/l, +92 %, p = 0.002). This increase in total bile acids was
      accompanied by a decrease in conjugated bile acids, which correlated with
      decreased glucose oxidation (r = 0.571, p = 0.002) and with increased lipid
      oxidation (r = -0.626, p = 0.0004). The change in taurine-conjugated bile acids
      correlated with altered DIO2 mRNA expression in adipose tissue (r = -0.498, p =
      0.013) potentially linking bile acid conjugation to substrate oxidation through
      DIO2. CONCLUSIONS: Fasting serum bile acid levels increase after RYGB. More
      specifically, changes in bile acid conjugation after RYGB associate with altered
      energy metabolism.

PMID- 22638682
TI  - Peritoneofascial suture method for facilitating loop ileostomy mobilization.
AB  - BACKGROUND: Ileostomy closure is a minor procedure and is performed through a
      small peristomal incision. However, a hard adhesion increases the technical
      difficulty. A peritoneofascial suture (PFS) will reduce the adhesion layers of
      the abdominal wall. This study was performed to evaluate whether the PFS method
      may decrease the extent of adhesions between the bowel and the abdominal wall
      opening and facilitate ileostomy mobilization. METHODS: Forty-two patients (24
      males and 18 females) with a mean age of 57 years (range = 31-80 years) and who
      were undergoing ileostomy closure were enrolled. The PFS group and the
      conventional group had 18 and 24 patients, respectively. The intraoperative
      findings such as degree of adhesion, mobilization time, and associated bowel
      injury were analyzed. RESULTS: The thickness of the abdominal wall and the rectus
      abdominis was similar in both groups. The overall operation time was shorter in
      the PFS group than in the conventional group (50.9 vs. 80.4 min, respectively, p
      = 0.001). The ileostomy mobilization time was also shorter in the PFS group than
      in the conventional group (18.9 vs. 44.7 min, respectively, p < 0.001). The
      procedure was technically easier in the PFS group more frequently than in the
      conventional group (77.8 % vs. 31.6 %, respectively, p = 0.013). Bowel injury
      during mobilization was more common in the conventional group than in the PFS
      group (50.0 % vs. 16.7 %, respectively, p = 0.053). CONCLUSIONS: The
      peritoneofascial suture method is a simple procedure, and it may facilitate
      ileostomy mobilization by decreasing adhesion layers. To confirm the technical
      advantage of this method a randomized study will be needed.

PMID- 22638683
TI  - Antibiotics as first-line therapy for acute appendicitis: evidence for a change
      in clinical practice.

PMID- 22638684
TI  - Tissue banking in a regional hospital: a promising future concept? First report
      on fresh frozen tissue banking in a hospital without an integrated institute of
      pathology.
AB  - BACKGROUND: Vital tissue provided by fresh frozen tissue banking is often
      required for genetic tumor profiling and tailored therapies. However, the
      potential patient benefits of fresh frozen tissue banking are currently limited
      to university hospitals. The objective of the present pilot study--the first one
      in the literature--was to evaluate whether fresh frozen tissue banking is
      feasible in a regional hospital without an integrated institute of pathology.
      METHODS: Patients with resectable breast and colon cancer were included in this
      prospective study. Both malignant and healthy tissue were sampled using isopentan
      based snap-freezing 1 h after tumor resection and stored at -80  degrees C before
      transfer to the main tissue bank of a University institute of pathology. RESULTS:
      The initial costs to set up tissue banking were 35,662 US$. Furthermore, the
      running costs are 1,250 US$ yearly. During the first 13 months, 43 samples (nine
      samples of breast cancer and 34 samples of colon cancer) were collected from 41
      patients. Based on the pathology reports, there was no interference with standard
      histopathologic analyses due to the sample collection. CONCLUSIONS: This is the
      first report in the literature providing evidence that tissue banking in a
      regional hospital without an integrated institute of pathology is feasible. The
      interesting findings of the present pilot study must be confirmed by larger
      investigations.

PMID- 22638694
TI  - CYP2D6 genotyping and use of antidepressants in breast cancer patients: test
      development for clinical application.
AB  - Approximately 25% of clinically important drugs and numerous environmental
      carcinogens are metabolised by CYP2D6. Variation in the CYP2D6 gene and
      concomitant use of tamoxifen (TAM) with certain antidepressants may increase
      recurrence risk in breast cancer patients due to reduced enzyme activity. In this
      study we determined the appropriateness of adding CYP2D6 genotyping to the breast
      cancer genetic testing options already available in South Africa, which include
      BRCA mutation screening and transcriptional profiling to assess estrogen receptor
      (ER) status. A total of 114 South African breast cancer patients, including 52
      Caucasian and 62 Coloured (Mixed ancestry), and 63 Caucasian control individuals
      were genotyped for the most common inactivating allele (CYP2D6*4, rs3892097)
      previously identified in the CYP2D6 gene. In the initial validation data set
      consisting of 25 Caucasian and 62 Coloured patients, the CYP2D6*4 allele
      frequency was significantly higher in Caucasian compared to Coloured patients
      (24% vs. 3%, p<0.001), similar to previous findings in the general South African
      population. Extended CYP2D6 genotyping was subsequently performed in an
      implementation data set of 27 Caucasian breast cancer patients, to determine the
      prevalence of depression and use of antidepressants in a clinical setting. A
      medical history of depression and/or use of antidepressants was reported in 37%
      (10/27) of these breast cancer patients genotyped for CYP2D6*4. This
      translational research study has led to increased awareness among clinicians of
      the potential benefits of CYP2D6 genotyping to facilitate prevention of
      cumulative risk in a high-risk genetic subgroup of breast cancer patients
      considered for concomitant treatment of TAM and antidepressants that may reduce
      enzyme function.

PMID- 22638695
TI  - Effect of histidine administration to female rats during pregnancy and lactation
      on enzymes activity of phosphoryltransfer network in cerebral cortex and
      hippocampus of the offspring.
AB  - Histidinemia is an inborn error of metabolism of amino acids caused by deficiency
      of histidase activity in liver and skin with consequent accumulation of histidine
      in plasma and tissues. Histidinemia is an autosomal recessive trait usually
      considered harmless to patients and their offspring, but some patients and
      children born from histidinemic mothers have mild neurologic alterations.
      Considering that histidinemia is one of the most frequently identified metabolic
      conditions, in the present study we investigated the effect of L-histidine load
      to female rats during pregnancy and lactation on some parameters of
      phosphoryltransfer network in cerebral cortex and hippocampus of the offspring.
      Pyruvate kinase, cytosolic and mitochondrial creatine kinase activities decreased
      in cerebral cortex and in hippocampus of rats at 21 days of age and this pattern
      remained in the cerebral cortex and in hippocampus at 60 days of age. Moreover,
      adenylate kinase activity was reduced in the cerebral cortex and in hippocampus
      of the offspring at 21 days of age, whereas the activity was increased in the two
      tissues at 60 days of age. These results suggest that administration of L
      histidine to female rats in the course of pregnancy and lactation could impair
      energy homeostasis in the cerebral cortex and hippocampus of the offspring.
      Considering that histidinemia is usually a benign condition and little attention
      has been given to maternal histidinemia, it seems important to perform more
      studies in the children born from histidinemic mothers.

PMID- 22638703
TI  - Improving quality of medical treatment and care: are surgeons' working conditions
      and job satisfaction associated to patient satisfaction?
AB  - BACKGROUND: Over the last decades, surgeons, researchers, and health
      administrators have been working hard to define standards for high-quality
      treatment and care in Surgery departments. However, it is unclear whether
      patients' perceptions of medical treatment and care are related and affected by
      surgeons' perceptions of their working conditions and job satisfaction. The aim
      of this study was to evaluate patients' satisfaction in relation to surgeons'
      working conditions. METHODS: A cross-sectional survey with 120 patients and 109
      surgeons working in Surgery hospital departments was performed. Surgeons
      completed a survey evaluating their working conditions and job satisfaction.
      Patients assessed quality of medical care and treatment and their satisfaction
      with being a patient in this department. RESULTS: Seventy percent of the patients
      were satisfied with performed surgeries and services in their department.
      Surgeons' job satisfaction and working conditions rated with moderate scores.
      Bivariate analyses showed correlations between patients' satisfaction and
      surgeons' job satisfaction and working conditions. Strongest correlations were
      found between kindness of medical staff, treatment outcome and overall patient
      satisfaction. CONCLUSION: This study demonstrates strong associations between
      surgeons' working conditions and patient satisfaction. Based on these findings,
      hospital managements should improve work organization, workload, and job
      resources to not only improve surgeons' job satisfaction but also quality of
      medical treatment and patient satisfaction in Surgery departments.

PMID- 22638707
TI  - Examining the relationship between specific cognitive processes and falls risk in
      older adults: a systematic review.
AB  - This systematic review aims to establish which cognitive domains are associated
      with falls or falls risk. Recent evidence suggests that impaired cognition
      increases seniors' risk of falling. The purpose of this review was to identify
      the cognitive domains that are significantly associated with falls or falls risk
      in older adults. We conducted a systematic review of peer-reviewed journal
      articles published from 1948 to present, focusing on studies investigating
      different domains of cognitive function and their association with falls or falls
      risk in adults aged 60 years or older. In accordance with Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses guidelines, we completed a
      comprehensive search of MEDLINE, PubMed, and EMBASE databases to identify studies
      examining the association between cognitive function and falls or falls risk.
      With an expert in the field, we developed a quality assessment questionnaire to
      rate the quality of the studies included in this systematic review. Twenty-five
      studies were included in the review. We categorized studies based on two related
      but distinct cognitive domains: (1) executive functions or (2) dual-task ability.
      Twelve studies reported a significant association between executive functions and
      falls risk. Thirteen studies reported that dual-task performance is a predictor
      of falls or falls risk in older adults. Three studies did not report an
      association between cognition and falls risk. Consistent evidence demonstrated
      that executive functions and dual-task performance were highly associated with
      falls or falls risk. The results from this review will aid healthcare
      professionals and researchers in developing innovative screening and treatment
      strategies for mitigating falls risk by targeting specific cognitive domains.

PMID- 22638704
TI  - Immune regulation by phospholipase C-beta isoforms.
AB  - Rapid progress has recently been made regarding how phospholipase C (PLC)-beta
      functions downstream of G protein-coupled receptors and how PLC-beta functions in
      the nucleus. PLC-beta has also been shown to interplay with tyrosine kinase-based
      signaling pathways, specifically to inhibit Stat5 activation by recruiting the
      protein-tyrosine phosphatase SHP-1. In this regard, a new multimolecular
      signaling platform, named SPS complex, has been identified. The SPS complex has
      important regulatory roles in tumorigenesis and immune cell activation.
      Furthermore, a growing body of work suggests that PLC-beta also participates in
      the differentiation and activation of immune cells that control both the innate
      and adaptive immune systems.

PMID- 22638708
TI  - Cost-effectiveness of nutritional intervention in elderly subjects after hip
      fracture. A randomized controlled trial.
AB  - Hip fracture patients can benefit from nutritional supplementation during their
      recovery. Up to now, cost-effectiveness evaluation of nutritional intervention in
      these patients has not been performed. Costs of nutritional intervention are
      relatively low as compared with medical costs. Cost-effectiveness evaluation
      shows that nutritional intervention is likely to be cost-effective. INTRODUCTION:
      Previous research on the effect of nutritional intervention on clinical outcome
      in hip fracture patients yielded contradictory results. Cost-effectiveness of
      nutritional intervention in these patients remains unknown. The aim of this study
      was to evaluate cost-effectiveness of nutritional intervention in elderly
      subjects after hip fracture from a societal perspective. METHODS: Open-label,
      multi-centre randomized controlled trial investigating cost-effectiveness of
      intensive nutritional intervention comprising regular dietetic counseling and
      oral nutritional supplementation for 3 months postoperatively. Patients allocated
      to the control group received care as usual. Costs, weight and quality of life
      were measured at baseline and at 3 and 6 months postoperatively. Incremental cost
      effectiveness ratios (ICERs) were calculated for weight at 3 months and quality
      adjusted life years (QALYs) at 6 months postoperatively. RESULTS: Of 152 patients
      enrolled, 73 were randomized to the intervention group and 79 to the control
      group. Mean costs of the nutritional intervention was 613 Euro. Total costs and
      subcategories of costs were not significantly different between both groups.
      Based on bootstrapping of ICERs, the nutritional intervention was likely to be
      cost-effective for weight as outcome over the 3-month intervention period,
      regardless of nutritional status at baseline. With QALYs as outcome, the
      probability for the nutritional intervention being cost-effective was relatively
      low, except in subjects aged below 75 years. CONCLUSION: Intensive nutritional
      intervention in elderly hip fracture patients is likely to be cost-effective for
      weight but not for QALYs. Future cost-effectiveness studies should incorporate
      outcome measures appropriate for elderly patients, such as functional limitations
      and other relevant outcome parameters for elderly.

PMID- 22638709
TI  - Relationship between use of antidepressants and risk of fractures: a meta
      analysis.
AB  - It has been shown that antidepressants would have a direct action on bone
      metabolism and would be associated with increased fracture risk. Results from
      this large meta-analysis show that both SSRIs and TCAs are associated with a
      moderate and clinically significant increase in the risk of fractures of all
      types. INTRODUCTION: This study seeks to investigate the relationship between use
      of antidepressants and the risk of fracture. METHODS: An exhaustive systematic
      research of case-control and cohort studies published or performed between 1966
      and April 2011 that reported risk estimates of fracture associated with use of
      antidepressants was performed using MEDLINE, PsycINFO, and the Cochrane
      Systematic Review Database, manual review of the literature, and congressional
      abstracts. Inclusion, quality scoring, and data abstraction were performed
      systematically by three independent reviewers. RESULTS: A total of 34 studies (n
      = 1,217,464 individuals) were identified. Compared with non-users, the random
      effects pooled RR of fractures of all types, among antidepressant users, were
      1.39 (95%CI 1.32-1.47). Use of antidepressants were associated with a 42 %, 47 %,
      and 38 % risk increase in non-vertebral, hip, and spine fractures, respectively
      ([For non-vertebral fractures: RR = 1.42, 95%CI 1.34-1.51]; [For hip fractures:
      RR = 1.47, 95%CI 1.36-1.58]; [For spine fractures: RR = 1.38, 95%CI 1.19-1.61]).
      Studies examining SSRI use showed systematically a higher increase in the risk of
      fractures of all types, non-vertebral, and hip fractures than studies evaluating
      TCA use. CONCLUSIONS: Results from this large meta-analysis show that both SSRIs
      and TCAs are associated with a moderate and clinically significant increase in
      the risk of fractures of all types.

PMID- 22638710
TI  - Updated fracture incidence rates for the Italian version of FRAX(r).
AB  - In order to update data underlying the Italian version of FRAX, we computed the
      national hip fracture incidence in Italy from hospitalization records for the
      year 2008. Mortality data and 10-year probabilities of major osteoporotic
      fractures were also updated. This revision will improve FRAX accuracy and
      reliability. INTRODUCTION: The original Italian version of FRAX(r) was based on
      five regional estimates of hip fracture risk undertaken up to 20 years
      previously. Our objective was to update hip fracture rates for the model with
      more recently derived data from the whole Italian population and more recent data
      on mortality. METHODS: We analyzed the Italian national hospitalization database
      for the year 2008 in order to compute age- and sex-specific hip fracture
      incidence rates. Re-hospitalisations of the same patients within 1 year were
      excluded from the analysis. Hip fracture incidence rates were computed for the
      age range of 40-100 years, whereas the original FRAX model lacked data on the
      youngest and oldest age groups. In addition, we used the national mortality data
      for the same year 2008 to update the model. Ten-year fracture probabilities were
      re-calculated on the basis of the new fracture incidence rates. RESULTS: The new
      hip fracture age- and sex-specific incidence rates were close to those used in
      the original FRAX tool, although some significant differences (not exceeding 25
      30 %) were found for men aged 65-75 years and women under 55 years of age. In
      general, the revision resulted in decreased estimated 10-year probabilities in
      the younger age groups, whilst those in the older age groups were slightly
      increased. CONCLUSIONS: The Italian version of FRAX has been updated using the
      new fracture incidence rates. The impact of these revisions on FRAX is likely to
      increase the accuracy and reliability of FRAX in estimating 10-year fracture
      probabilities.

PMID- 22638711
TI  - Discrimination of fractures by low-frequency axial transmission ultrasound in
      postmenopausal females.
AB  - SUMMARY: In this cross-sectional study, 95 postmenopausal women, with and without
      fracture history, were measured by low-frequency axial transmission ultrasound.
      The measured ultrasound velocity discriminated the fractured subjects from the
      nonfractured ones equally or better than peripheral quantitative computed
      tomography (pQCT) and dual energy x-ray absorptiometry (DXA). These results
      suggest that low-frequency ultrasound is suitable for bone fragility assessment.
      INTRODUCTION: Quantitative low-frequency axial transmission ultrasound is a
      promising modality for assessing mineral density and geometrical properties of
      long bones such as radius and tibia. The aim of the current study was to evaluate
      the ability of low-frequency axial transmission ultrasound to discriminate
      fractures retrospectively in postmenopausal women. METHODS: A cross-sectional
      study involved 95 female subjects aged 45-88 years, whose fracture information
      was gathered retrospectively. The fracture group was defined as subjects with one
      or more low-/moderate-energy fractures. The radius and tibial shaft were measured
      with a custom-made ultrasonometer to assess the velocity of the low-frequency
      first-arriving signal (V (LF)). Site-matched pQCT was used to measure volumetric
      cortical and subcortical bone mineral density (sBMD), and cortical thickness
      (CTh). Areal BMD (aBMD) was measured using DXA for the whole body (WB), lumbar
      spine, and hip. RESULTS: The majority (19/32; 59 %) of the fractures were in the
      upper limb. V (LF) in the radius, but not in the tibia, discriminated fractures
      with an age- and BMI-adjusted odds ratio (OR) of 2.06 (95 % CI 1.21-3.50, p <
      0.01). In the radius, CTh and cortical BMD (CBMD) significantly discriminated
      fractures, as did the total, cortical, and sBMD in the tibia (adjusted OR 1.35
      2.15, p < 0.05). Sensitivity and specificity were similar among all the
      measurements (area under the receiver operating characteristic curve 0.74-0.81, p
      < 0.001). CONCLUSIONS: Low-frequency axial transmission ultrasound in the radius
      was able to discriminate fractured subjects from the nonfractured ones. This
      suggests that low-frequency axial transmission ultrasound has the potential to
      assess bone fragility in postmenopausal women.

PMID- 22638712
TI  - Analysis of the association between bisphosphonate treatment survival in Danish
      hip fracture patients-a nationwide register-based open cohort study.
AB  - Bisphosphonate (BP) users have decreased mortality, but this could be due to
      channeling bias. National healthcare data on hip fracture showed lower mortality
      in patients who were treated prior to fracture or began treatment after fracture.
      Reduced mortality after only one prescription filled points to the importance of
      patient factors. INTRODUCTION: Use of bisphosphonates has been found to be
      associated with decreased mortality even when adjusted for sex, frailty, bone
      mineral density and comorbidity, but BP may chiefly be initiated in patients with
      osteoporosis whose life expectancy is judged to be good. Our aim was to
      investigate the association between BP initiated before or after a hip fracture
      with mortality, and any modifying effects of comorbid conditions and recurrent
      fracture. METHODS: This register-based cohort study used prescription and
      mortality information for Danish patients born <=1945 experiencing a hip fracture
      between 1/Jan/1999 and 31/Dec/ 2002 (N = 42,076). Patients who began BP after hip
      fracture were compared with hip fracture patients who remained alive at the time
      when their matched index case began treatment. RESULTS: Patients who used BP
      prior to their hip fracture (4.6 %) had significantly lower 3-month mortality
      (adjusted odds ratio, OR, 0.68; 0.59-0.77). Patients who began BP after the
      fracture (2.6 %) had significantly decreased mortality, both for patients who
      filled only one prescription (adjusted hazard ratio, HR 0.84; 0.73-0.95) and for
      patients who filled multiple prescriptions HR 0.73 (0.61-0.88). There was a
      significant interaction by gender with no significant risk reduction in men.
      CONCLUSION: This national dataset shows significantly and substantially improved
      survival in women who receive BP before or after their hip fracture. However, the
      observation of a reduction in mortality in patients who filled only one
      prescription for a BP suggests that patient factors may account for a
      considerable part of the survival advantage observed with BPs.

PMID- 22638717
TI  - Infantile achalasia cardia with pelvi-ureteric junction obstruction.

PMID- 22638713
TI  - Hospitalisations for fracture and associated costs between 2000 and 2009 in
      Ireland: a trend analysis.
AB  - In Ireland, the absolute numbers of hospitalisations for all osteoporotic-type
      fractures including hip fractures increased between 2000 and 2009 along with the
      mean length of stay. The cost of hospitalisations for these fractures also
      increased between 2003 and 2008. INTRODUCTION: The purposes of the study were to
      carry out a trend analyses of the total number of osteoporotic-type fractures in
      males and females aged 50 years and over in Ireland between 2000 and 2009 and to
      project the number of osteoporotic-type fractures in the Republic of Ireland
      expected by 2025. METHODS: Age- and gender-specific trends in the absolute
      numbers and direct age-standardised rates of hospitalisations for all
      osteoporotic-type fractures in men and women >= 50 years were analysed, along
      with the associated hospitalisation costs and length of stay using the Hospital
      In-Patient Enquiry system database. Future projections of absolute numbers of
      osteoporotic-type fractures in years 2015, 2020 and 2025 were computed based on
      the 2009 incidence rates applied to the projected populations. RESULTS: Between
      2000 and 2009, the absolute numbers of all osteoporotic-type fractures increased
      by 12 % in females and by 15 % in males while the absolute numbers of hip
      fractures increased by 7 % in women and by 20 % in men. The age-specific rates
      for hip fractures decreased in all age groups with the exception of the 55-59
      year age group which showed an increase of 4.1 % (p = 0.023) within the study
      period. The associated hospitalisation costs and length of stay increased.
      Assuming stable age-standardised incidence rates from 2009 over the next 20
      years, the number of all types of osteoporotic-type fractures is projected to
      increase by 79 % and the number of hip fractures is expected to increase by 88 %
      by 2025. CONCLUSIONS: Hospitalisations for osteoporotic-type fractures continued
      to increase in Ireland. Hip fractures increased by 7 % in women and 20 % in men.

PMID- 22638718
TI  - Air and hair - perforating trichobezoar.

PMID- 22638719
TI  - The human locus coeruleus 3-D stereotactic anatomy.
AB  - PURPOSE: The main goal of this work was to study the stereotactic anatomy of the
      human locus coeruleus (LC), important relay of adrenergic and dopaminergic human
      brainstem (HB) circuitry, to allow its easy localization on MRI and in
      microsurgical procedures. METHODS: Forty LC were studied from 20 adult HB of both
      sexes. The melanin pigmentation of its cells was used to identify and localize
      them and so to define the 2-D and 3-D LC contours. These HB were cut on a
      cryomicrotome with 3-D referenciation. The slices were coloured with
      haematoxyline-eosin. On the slices, digitized images of the cells were referenced
      to the midline, the fourth ventricle floor plane and the pontomedullary junction
      plane with an appropriate computer program. RESULTS: The LC revealed to be a
      symmetric, thin and elongated nucleus, divergent caudally except in its superior
      part, with a sub-ependymal location on the superior dorsal lateral pons. The main
      LC dimensions are: length 12.0-17.0 mm (m 14.5); width 2.5 mm; height 2.0 mm. The
      3-D references of the LC center are: 3.2 +/- 0.3 mm to the midline; 1.1 +/- 0.2
      mm to the IV ventricle floor and 18.5 +/- 1.5 mm to the ponto-medullary junction.
      CONCLUSIONS: The human LC is a nucleus thinner and longer than previously
      described (in average 14.5 mm long and 2-2.5 mm thick), localized 1 mm under the
      IV ventricle, 3 mm apart from the midline and centered 14-21 mm above de ponto
      medullary junction. No correlation was found between LC and pons dimensions, the
      gender or the age.

PMID- 22638720
TI  - Compartments of the foot: topographic anatomy.
AB  - Recent publications have renewed the debate regarding the number of foot
      compartments. There is also no consensus regarding allocation of individual
      muscles and communication between compartments. The current study examines the
      anatomic topography of the foot compartments anew using 32 injections of epoxy
      resin and subsequent sheet plastination in 12 cadaveric foot specimens. Six
      compartments were identified: dorsal, medial, lateral, superficial central, deep
      forefoot, and deep hindfoot compartments. Communication was evident between the
      deep hindfoot compartment and the superficial central and deep central forefoot
      compartments. In the hindfoot, the neurovascular bundles were located in separate
      tissue sheaths between the central hindfoot compartment and the medial
      compartment. In the forefoot, the medial and lateral bundles entered the deep
      central forefoot compartment. The deep central hindfoot compartment housed the
      quadratus plantae muscle, and after calcaneus fracture could develop an isolated
      compartment syndrome.

PMID- 22638721
TI  - An anatomic study of structure and innervation of the serratus anterior muscle.
AB  - BACKGROUND: The structure and function of the serratus anterior muscle are
      partitioned into three parts. If the morphological characteristics in each part
      can be demonstrated in more detail, the cause of dysfunction will probably be
      identifiable more accurately. The purpose of this study was to demonstrate the
      details of the structure and innervation in each part of the serratus anterior
      muscle. MATERIALS AND METHODS: This macroscopic anatomic study was conducted
      using ten sides from five cadavers. The structure and innervation in each part of
      this muscle were examined. RESULTS: In the superior part, the independent branch
      was divided from a branch innervating the levator scapulae muscle. In the middle
      part, the long thoracic nerve descended on one-third of the anterior region
      between the origin and insertion. In the inferior part, the long thoracic nerve
      which ramified into many branches and branches from the intercostal nerves were
      distributed on all sides. CONCLUSION: This study demonstrated that the
      innervation of the serratus anterior muscle was different in each part. The
      difference indicates that the superior part has an intimate relation with the
      levator scapulae muscle while the middle and inferior parts could be the actual
      serratus anterior muscle. Moreover, the distribution of branches from the
      intercostal nerves shows that the inferior part has a connection with some trunk
      elements. Understanding these characteristics of innervation is useful to
      identify the cause of dysfunction. In addition, we assert that the constant
      distribution of branches from the intercostal nerves is significant for the
      morphology.

PMID- 22638722
TI  - Determination of trace metals in drinking water in Irbid City-Northern Jordan.
AB  - Drinking water samples from Irbid, the second populated city in Jordan were
      analyzed for trace metals (As, Ba, Cd, Pb, Cr, Cu, Fe, Zn, Mn, Ni, and Se)
      content. The study was undertaken to determine if the metal concentrations were
      within the national and international guidelines. A total of 90 drinking water
      samples were collected from Al-Yarmouk University area. The samples were
      collected from three different water types: tap water (TW), home-purified water
      (HPW), and plant-purified water (PPW). All the samples were analyzed for trace
      metals using an inductively coupled plasma-optical emission spectrometry. All the
      samples analyzed were within the United States Environmental Protection Agency
      admissible pH limit (6.5-8.5). The results showed that concentrations of the
      trace metals vary significantly between the three drinking water types. The
      results showed that HPW samples have the lowest level of trace metals and the
      concentrations of some essential trace metals in these samples are less than the
      recommended amounts. Slight differences in the metal contents were found between
      HPW samples, little differences between PPW samples; however, significant
      differences were found between TW samples. Although some TW samples showed high
      levels of trace metals, however, the mean level of most elements determined in
      the samples were well within the Jordanian standards as well as the World Health
      Organization standards for drinking water.

PMID- 22638723
TI  - Mapping of fluoride endemic area and assessment of F(-1) accumulation in soil and
      vegetation.
AB  - The prevalence of fluorosis is mainly due to the consumption of more fluoride (F(
      1)) through drinking water, vegetables, and crops. The objective of the study was
      mapping of F(-1) endemic area of Newai Tehsil, Tonk district, Rajasthan, India.
      For the present study, water, soil (0-45 cm), and vegetation samples were
      collected from 17 villages. Fluoride concentration in water samples ranged from
      0.3 to 9.8 mg/l. Out of 17 villages studied, the amounts of F(-1) content of
      eight villages were found to exceed the permissible limits. Labile F(-1) content
      and total F(-1) content in soil samples ranges 11.00-70.05 mg/l and 50.3-179.63
      MUg g(-1), respectively. F(-1) content in tree species was found in this order
      Azadirachta indica 47.32-55.76 MUg g(-1) > Prosopis juliflora 40.16-49.63 MUg g(
      1) > Acacia tortilis 34.39-43.60 MUg g(-1). While in case of leafy vegetables, F(
      1) content order was Chenopodium album 54.23-98.42 MUg g(-1) > Spinacea oleracea
      30.41-64.09 MUg g(-1) > Mentha arvensis 35.48-51.97 MUg g(-1). The order of F(-1)
      content in crops was found as 41.04 MUg g(-1) Pennisetum glaucum > 13.61 MUg g(
      1) Brassica juncea > 7.98 MUg g(-1) Triticum sativum in Krishi Vigyan Kendra
      (KVK) farms. Among vegetation, the leafy vegetables have more F(-1) content. From
      the results, it is suggested that the people of KVK farms should avoid the use of
      highly F(-1) containing water for irrigation and drinking purpose. It has been
      recommended to the government authority to take serious steps to supply drinking
      water with low F(-1) concentration for the fluorosis affected villages. Further,
      grow more F(-1) hyperaccumulator plants in F(-1) endemic areas to lower the F(-1)
      content of the soils.

PMID- 22638724
TI  - Regional assessment of marine and estuarine sediment toxicity in Southern
      California, USA.
AB  - Sediment toxicity was investigated at 222 stations in the Southern California
      Bight (SCB) during 2008. This represented the first time that assessment methods
      established by California's new Sediment Quality Objectives program were employed
      in a survey of this scale. The goal was to determine the extent and magnitude of
      sediment toxicity in the SCB, how toxicity compared among specific environments,
      and whether toxicity has changed over the last decade. Two toxicity tests were
      used: the 10-day amphipod whole sediment survival test with Eohaustorius
      estuarius and a 48-h embryo development test with the mussel Mytilus
      galloprovincialis exposed at the sediment-water interface. Less than 1 % of the
      area of the SCB was found to be toxic to the amphipod test. No toxicity was found
      in offshore stations, but 14 % of embayment areas were toxic to the amphipods.
      The mussel test identified 13 % of the embayment areas to be toxic. Estuary and
      marina locations had the greatest areal extent of toxicity for both tests. The
      two toxicity methods agreed that sediments were not toxic at over half of the
      stations tested. The mussel test showed a greater magnitude of response than the
      amphipod. Sediment toxicity was shown to have declined in both extent and
      magnitude from levels measured in 1998 and 2003.

PMID- 22638725
TI  - Toxicity assessment of textile effluents treated by advanced oxidative process
      (UV/TiO2 and UV/TiO2/H2O2) in the species Artemia salina L.
AB  - Textile industry wastes raise a great concern due to their strong coloration and
      toxicity. The objective of the present work was to characterize the degradation
      and mineralization of textile effluents by advanced oxidative processes using
      either TiO(2) or TiO(2)/H(2)O(2) and to monitor the toxicity of the products
      formed during 6-h irradiation in relation to that of the in natura effluent. The
      results demonstrated that the TiO(2)/H(2)O(2) association was more efficient in
      the mineralization of textile effluents than TiO(2), with high mineralized ion
      concentrations (NH (4) (+) , NO (3) (-) , and SO (4) (2-) ) and significantly
      decreased organic matter ratios (represented by the chemical oxygen demand and
      total organic carbon). The toxicity of the degradation products after 4-h
      irradiation to Artemia salina L. was not significant (below 10 %). However, the
      TiO(2)/H(2)O(2) association produced more toxicity under irradiation than the
      TiO(2) system, which was attributed to the increased presence of oxidants in the
      first group. Comparatively, the photogenerated products of both TiO(2) and the
      TiO(2)/H(2)O(2) association were less toxic than the in natura effluent.

PMID- 22638726
TI  - Synchronization with competing visual and auditory rhythms: bouncing ball meets
      metronome.
AB  - Synchronization of finger taps with periodically flashing visual stimuli is known
      to be much more variable than synchronization with an auditory metronome. When
      one of these rhythms is the synchronization target and the other serves as a
      distracter at various temporal offsets, strong auditory dominance is observed.
      However, it has recently been shown that visuomotor synchronization improves
      substantially with moving stimuli such as a continuously bouncing ball. The
      present study pitted a bouncing ball against an auditory metronome in a target
      distracter synchronization paradigm, with the participants being auditory experts
      (musicians) and visual experts (video gamers and ball players). Synchronization
      was still less variable with auditory than with visual target stimuli in both
      groups. For musicians, auditory stimuli tended to be more distracting than visual
      stimuli, whereas the opposite was the case for the visual experts. Overall, there
      was no main effect of distracter modality. Thus, a distracting spatiotemporal
      visual rhythm can be as effective as a distracting auditory rhythm in its
      capacity to perturb synchronous movement, but its effectiveness also depends on
      modality-specific expertise.

PMID- 22638727
TI  - Conventional MRI does not reliably distinguish radiation necrosis from tumor
      recurrence after stereotactic radiosurgery.
AB  - Distinguishing radiation necrosis (RN) from tumor recurrence after stereotactic
      radiosurgery (SRS) for brain metastases is challenging. This study assesses the
      sensitivity (SN) and specificity (SP) of an MRI-based parameter, the "lesion
      quotient" (LQ), in characterizing tumor progression from RN. Records of patients
      treated with SRS for brain metastases between 01/01/1999 and 12/31/2009 and with
      histopathologic analysis of a subsequent contrast enhancing enlarging lesion at
      the treated site at a single institution were examined. The LQ, the ratio of
      maximal nodular cross sectional area on T2-weighted imaging to the corresponding
      maximal cross sectional area of T1-contrast enhancement, was calculated by a
      neuroradiologist blinded to the histopathological outcome. Cutoffs of <0.3, 0.3
      0.6, and >0.6 have been previously suggested to have correlated with RN, mixed
      findings and tumor recurrence, respectively. These cutoff values were evaluated
      for SN, SP, positive predictive value (PPV) and negative predictive value (NPV).
      Logistic regression analysis evaluated for associated clinical factors. For the
      51 patients evaluated, the SN, SP, PPV and NPV for identifying RN (LQ < 0.3) were
      8, 91, 25 and 73 %, respectively. For the combination of recurrent tumor and RN
      (LQ 0.3-0.6) the SN, SP, PPV and NPV were 0, 64, 0 and 83 %. The SN, SP, PPV and
      NPV of the LQ for recurrent tumor (LQ > 0.6) were 59, 41, 62 and 39 %,
      respectively. Standard MRI techniques do not reliably discriminate between tumor
      progression and RN after treatment with SRS for brain metastases. Additional
      imaging modalities are warranted to aid in distinguishing between these
      diagnoses.

PMID- 22638732
TI  - Arsenic: an ancient toxicant of continuous public health impact, from Iceman Otzi
      until now.

PMID- 22638733
TI  - Association between the chemokine receptor 5 delta32 polymorphism and rheumatoid
      arthritis: a meta-analysis.
AB  - OBJECTIVE: The aim of this study was to determine whether the functional
      chemokine receptor 5 delta32 (CCR5-Delta32) polymorphism confers susceptibility
      to rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). METHODS:
      Meta-analysis was conducted on associations between the CCR5-Delta32 polymorphism
      and RA and JIA using (1) allele contrast and (2) the recessive, (3) the dominant,
      and (4) the additive models. RESULTS: Eleven population comparisons based on the
      data obtained from nine studies involving 13,412 subjects (RA 3,848, controls
      4,095; JIA 1,599, controls 3,870) were considered. In all study subjects, meta
      analysis showed a significant negative association between RA and the CCR5
      Delta32 allele (OR = 0.771, 95 % CI = 0.694-0.866, p = 6.5 * 10(-7)).
      Stratification by ethnicity indicated a significant association between the CCR5
      Delta32 allele and RA in Europeans (OR = 0.8001, 95 % CI = 0.709-0.904, p = 3.2 *
      10(-5)). Meta-analysis showed associations between the CCR5-Delta32 allele and
      JIA in Europeans and oligoarticular type (OR = 0.797, 95 % CI = 0.690-0.921, p =
      0.002; OR = 0.475, 95 % CI = 0.352-0.693, p = 9.5 * 10(-8)). CONCLUSIONS: This
      meta-analysis demonstrates that the CCR5-Delta32 polymorphism may confer
      susceptibility to RA and JIA in Europeans, and suggests that the CCR5-Delta32
      allele protects against the development of RA and JIA.

PMID- 22638734
TI  - The long-term efficacy of cilostazol in addition to dual antiplatelet therapy
      after sirolimus-eluting stent implantation for Japanese patients: an analysis of
      the 3-year follow-up outcomes from the j-Cypher registry.
AB  - Several clinical studies have reported the use of cilostazol in addition to
      aspirin and thienopyridine (triple antiplatelet therapy, TAPT) after percutaneous
      coronary intervention (PCI) decreases clinical events. However, the efficacy and
      safety of TAPT have not been fully evaluated in Japan. The prospectively
      collected data from 12824 Japanese patients received PCI as part of the j-Cypher
      Registry were analyzed. We selected 10356 patients who exclusively received
      implantation of sirolimus-eluting stents (SES), and compared the data from 10128
      patients who received dual antiplatelet therapy (aspirin + thienopyridine, DAPT)
      with 228 patients who received TAPT at the time of discharge. Patients who
      received TAPT had more comorbidities, such as peripheral vascular disease, renal
      failure with hemodialysis or insulin dependent diabetes mellitus, and more
      patients received stenting for the left main trunk. The cardiovascular event
      rates at 3 years after PCI in the TAPT group were not significantly different
      from DAPT group, even after adjusted risks for cardiovascular events; all-cause
      death (7.8 vs. 6.7 %, log-rank p = 0.44, adjusted Hazard Ratio [HR] 0.88: 95 %
      confidence interval [CI] 0.52-1.38, p = 0.61), myocardial infarction (1.7 vs. 2.4
      %, log-rank p = 0.49 and HR 0.71: 95 % CI 0.20-1.57, p = 0.40), target legion
      revascularization (12.7 vs. 9.9 %, log-rank p = 0.11 and HR 1.05: 95 % CI 0.71
      1.50, p = 0.91) and stroke (3.9 vs. 3.2 %, log-rank p = 0.52 and HR 1.09: 95 % CI
      0.52-2.00, p = 0.80). In conclusion, TAPT after SES implantation was associated
      with similar long-term clinical outcomes as DAPT in Japanese real-world clinical
      practice, although we did not evaluate the bleeding outcome.

PMID- 22638735
TI  - Antitumor carboplatin is more toxic in tumor cells when photoactivated: enhanced
      DNA binding.
AB  - Carboplatin, an analogue of "classical" cis-diamminedichloridoplatinum(II)
      (cisplatin), is a widely used second-generation platinum anticancer drug.
      Cytotoxicity of cisplatin and carboplatin is mediated by platinum-DNA adducts.
      Markedly higher concentrations of carboplatin are required, and the rate of
      adduct formation is considerably slower. The reduced toxic effects in tumor cells
      and a more acceptable side-effect profile are attributable to the lower
      reactivity of carboplatin with nucleophiles, since the cyclobutanedicarboxylate
      ligand is a poorer leaving group than the chlorides in cisplatin. Recently,
      platinum complexes were shown to be particularly attractive as potential
      photochemotherapeutic anticancer agents. Selective photoactivation of platinum
      complexes by irradiation of cancer cells may avoid enhancement of toxic side
      effects, but may increase toxicity selectively in cancer cells and extend the
      application of photoactivatable platinum complexes to resistant cells and to a
      wider range of cancer types. Therefore, it was of interest to examine whether
      carboplatin can be affected by irradiation with light to the extent that its DNA
      binding and cytotoxic properties are altered. We have found that carboplatin is
      converted to species capable of enhanced DNA binding by UVA irradiation and
      consequently its toxicity in cancer cells is markedly enhanced. Recent advances
      in laser and fiber-optic technologies make it possible to irradiate also internal
      organs with light of highly defined intensity and wavelength. Thus, carboplatin
      is a candidate for use in photoactivated cancer chemotherapy.

PMID- 22638739
TI  - Two patients of left lung cancer with right aortic arch: review of eight
      patients.
AB  - We report two cases of left lung cancer in patients with variant right aortic
      arches. Preoperative heart examination ascertained that neither patient had
      congenital heart disease. Patient 1 exhibited a right aortic arch with mirror
      image branching of the major arteries. The patient's clinical stage was T1aN0M0
      stage IA. Patient 2 exhibited a right aortic arch with an aberrant left
      subclavian artery. The patient received induction chemotherapy for cT2aN2M0 stage
      IIIA adenocarcinoma of the lung. In patients with a right aortic arch undergoing
      surgery, especially mediastinal lymph node dissection, it is important to
      consider the anatomical displacement of the vagus and recurrent laryngeal nerves
      in addition to the vascular abnormalities. In this study, we found that
      preoperative identification of anomalous structures using three-dimensional
      computed tomography was particularly useful in evaluating the anatomical location
      and position of the left recurrent laryngeal nerve from an embryological point of
      view.

PMID- 22638740
TI  - Surgical intervention for small-cell lung cancer: what is the surgical role?
AB  - Small-cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma that
      accounts for approximately 10-15% of all lung cancer cases. This histological
      subtype is a distinct entity with biological and oncological features differing
      from non-small cell lung cancer (NSCLC). Treatment is mainly performed using
      systemic chemotherapy, although surgery in association with chemotherapy may be
      indicated for a minor proportion of limited-disease cases. Since the outcomes
      after surgical intervention in patients with very early disease are comparable to
      those for NSCLC, accurate clinical staging is required, particularly in terms of
      nodal involvement. In addition to conventional mediastinoscopy, positron emission
      tomography-computed tomography and endobronchial ultrasonography guided
      transbronchial needle aspiration have recently become available for node
      diagnosis. The significance of surgery for SCLC includes local disease control
      and treatment for cases showing mixed histology. However, only two randomized
      control studies have examined the efficacy of surgery in SCLC, and both yielded
      negative results and are out of date. We review herein several studies concerning
      surgery for SCLC and discuss the results from a practical standpoint. A
      prospective trial performed in collaboration with pulmonologists is required to
      address the significance of surgery, which is a limited option in the treatment
      of SCLC.

PMID- 22638741
TI  - Glomus tumour: a rare differential diagnosis of bronchial obstruction in a
      smoker.
AB  - Tracheo-bronchial glomus tumours are rare, usually benign tumours of modified
      smooth muscle cells. They commonly present as non-specific respiratory symptoms
      of cough, dyspnoea or haemoptysis. Generally, glomus tumours are benign, but
      extension beyond the bronchial wall into surrounding soft tissues has been
      described. Surgical treatment remains the treatment of choice for tracheo
      bronchial glomus tumours. Endobronchial therapy should be considered in patients
      unfit for surgical excision. We describe a patient with a glomus tumour of the
      left main bronchus, who presented with mediastinal shift and lung atelectasis,
      treated by left upper sleeve lobectomy. The resection was complete and the
      patient was discharged home after 8 days from surgery.

PMID- 22638742
TI  - Brain swelling in acute superior vena cava syndrome due to aortic dissection:
      unusual and lethal manifestation aggravated by induction of general anesthesia.
AB  - A 32-year-old woman with Marfan syndrome experienced acute superior vena cava
      syndrome due to aortic dissection. The patient had previously undergone a Bentall
      operation. The aneurysm from the ascending to the transverse aorta compressed the
      superior vena cava, the right pulmonary artery, and the trachea. The rare and
      life-threatening neurological complication in this patient may have been related
      to brain edema, which was revealed by preoperative computed tomography. The
      induction of general anesthesia aggravated the symptoms of the superior vena cava
      syndrome and led to a fatal condition. Additional cannulation in the right
      subclavian vein was mandatory to alleviate the symptoms because the venous
      drainage from the upper half of the body created only by the femorofemoral bypass
      was not adequate. Total arch replacement was performed. The postoperative course
      was uneventful.

PMID- 22638743
TI  - Vascular occlusion device closure of bronchial stump fistulae: a straightforward
      approach to manage bronchial stump breakdown.
AB  - Post lung resection surgery bronchopleural fistula (BPF) continues to be a
      dangerous complication associated with very high mortality and morbidity.
      Traditional treatments have included primary closure of the fistula with muscle
      flaps and thoracic window formation. New techniques for secondary stump closure
      have included glues, stents and coils. We report another bronchoscopic treatment
      of BPF using an atrial septal closure/vascular occlusion device combined with
      bioglue.

PMID- 22638755
TI  - Antimicrobial therapy of febrile complications after high-dose chemotherapy and
      autologous hematopoietic stem cell transplantation--guidelines of the Infectious
      Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology
      (DGHO).
AB  - More than 18,000 autolgous transplantation were performed in Europe in the year
      2009. It as a routine procedure in experienced centres. Even if there is a low
      mortality rate, infections are a major issue after transplantation, occurring in
      more than 60 % of the patients. In this review we discuss all aspects of
      infections after autologous stem transplantation, including epidemiology,
      diagnostics, therapeutic algorithms, prophylaxis and supportive therapy.

PMID- 22638757
TI  - Recurrent superior vena cava syndrome caused by IgD multiple myeloma.

PMID- 22638756
TI  - Perceived information provision and satisfaction among lymphoma and multiple
      myeloma survivors--results from a Dutch population-based study.
AB  - To improve posttreatment care for (long-term) lymphoma survivors in the
      Netherlands, survivorship clinics are being developed. As information provision
      is an important aspect of survivorship care, our aim was to evaluate the current
      perceived level of and satisfaction with information received by non-Hodgkin's
      lymphoma (NHL), Hodgkin's lymphoma (HL) and multiple myeloma (MM) survivors, and
      to identify associations with sociodemographic and clinical characteristics. The
      population-based Eindhoven Cancer Registry was used to select all patients
      diagnosed with NHL, HL and MM from 1999 to 2009. In total, 1,448 survivors
      received a questionnaire, and 1,135 of them responded (78.4 %). The EORTC QLQ
      INFO25 was used to evaluate the perceived level of and satisfaction with
      information. Two thirds of survivors were satisfied with the amount of received
      information, with HL survivors being most satisfied (74 %). At least 25 % of
      survivors wanted more information. Young age, having had chemotherapy, having
      been diagnosed more recently, using internet for information and having no
      comorbidities were the most important factors associated with higher perceived
      levels of information provision. Although information provision and satisfaction
      with information seems relatively good in lymphoma and MM survivors, one third
      expressed unmet needs. Furthermore, variations between subgroups were observed.
      Good information provision is known to be associated with better quality of life.
      Survivorship care plans could be a way to achieve this.

PMID- 22638758
TI  - Hb Etobicoke mutation in a hybrid HBA212 allele [HBA212 84 (F5) Ser>Arg;
      HBA212:c.255C>G].

PMID- 22638759
TI  - Longitudinal relationships between workplace bullying and psychological distress.
AB  - OBJECTIVES: The aims of this study were to examine reciprocal longitudinal
      associations between exposure to workplace bullying and symptoms of psychological
      distress and to investigate how self-labeled victimization from bullying explains
      the effects of bullying on health. METHODS: Logistic regression analysis was
      employed to examine the longitudinal relationships between workplace bullying and
      psychological distress in a representative cohort sample of 1775 Norwegian
      employees. The time-lag between baseline and follow-up was two years. Exposure to
      bullying behavior was measured with the revised version of the Negative Acts
      Questionnaire. Perceived victimization from bullying was measured by a single
      self-labeling question. Psychological distress was measured with the 25-item
      Hopkins Symptom Checklist. All variables were measured at both baseline and
      follow-up. RESULTS: After adjustment for psychological distress at baseline,
      exposure to bullying behavior [odds ratio (OR) 1.68, 95% confidence interval (95%
      CI) 1.07-2.62) was found to predict subsequent psychological distress. This
      effect of bullying behaviors disappeared when victimization from bullying (OR
      2.47, 95% CI 1.17-5.22) was entered into the regression. Both psychological
      distress (OR 2.49, 95% CI 1.64-3.80) and victimization (OR 2.61, 95% CI 1.42
      4.81) at baseline were associated with increased risks of being a target of
      bullying behaviors at follow-up. Psychological distress (OR 2.51, 95% CI 1.39
      4.52) and bullying behaviors (OR 2.95, 95% CI 1.39-4.52) at follow-up were
      associated with victimization. CONCLUSION: The mutual relationship between
      bullying and psychological distress indicates a vicious circle where bullying and
      distress reinforce their own negative effects. This highlights the importance of
      early interventions to stop workplace bullying and provide treatment options to
      employees with psychological distress.

PMID- 22638760
TI  - Intravesical epinephrine preserves uroplakin II expression in urinary bladder
      from cyclophosphamide-induced rat cystitis.
AB  - We investigated the attenuated effect of intravesical epinephrine (EPI) on
      uroplakin II (UPII) expression in cyclophosphamide (CYP)-induced rat cystitis.
      Sixty-eight Sprague-Dawley female rats were divided into one negative control
      group (GI) and five intraperitoneally CYP (150 mg CYP/kg)-injected groups (GII
      VI) consisting of a positive control group (GII), three groups (GIII-V) with
      retaining intravesically instillated ameliorating agents for 90 min by urethral
      ligation until sacrifice, and one group (GVI) with freely voiding after
      intravesical EPI instillation. The retention groups were further classified into
      null-treated- (GIII), EPI- (GIV), and vehicle group (GV). All rats were
      euthanized 24 h after CYP injection. The UPII and alpha1-adrenergic receptors
      (AR) levels were measured with real-time polymerase chain reaction (RT-PCR)
      method and the morphological changes were also evaluated. CYP induced severe
      cystitis and decreased vesical UPII mRNA level. The EPI-treated groups had showed
      attenuation effects against submucosal edema and hemorrhage, and preserved UPII
      expression. Concurrently, intravesical EPI resulted in a significant preservation
      of both subtypes of alpha1A- and alpha1B AR expressions, which was well
      correlated with the hemostatic pattern in the samples. The obstructed and null
      treated group (GIII) revealed severe cystitis and maximally decreased UPII
      levels, and the diluting effect of vehicle (GV) on CYP toxicity was insignificant
      on UPII preservation. The UPII level of RT-PCR was well correlated with the UPII
      immunohistological expression and their morphological changes. Intravesical
      instillation of EPI preserves UPII expression and attenuates the toxic responses
      in the bladder in CYP-induced rat cystitis.

PMID- 22638768
TI  - Urothelial carcinoma with abundant myxoid stroma: evidence for mucus production
      by cancer cells.

PMID- 22638761
TI  - Fasitibant prevents the bradykinin and interleukin 1beta synergism on
      prostaglandin E2 release and cyclooxygenase 2 expression in human fibroblast-like
      synoviocytes.
AB  - This study investigates the effect of the selective and potent B(2) receptor
      antagonist fasitibant (MEN16132) on the proinflammatory effect of bradykinin (BK)
      and its interaction with interleukin 1beta (IL-1beta) in human synoviocytes.
      PGE(2) content was detected in the surnatants and COX-2 and COX-1 gene and
      protein expression determined in the cells. Radioligand binding ([(3) H]BK) and
      BK-induced inositolphosphate experiments were performed. Incubation of
      synoviocytes with BK induced a sustained production of PGE(2) and transient COX-2
      gene expression that were prevented by pretreatment with fasitibant (1 MUM, 30
      min preincubation). IL-1beta increased PGE(2) release and COX-2 expression more
      than BK alone. The combined treatment of cells with BK and IL-1beta induced an
      even increase of released PGE(2) and COX-2 gene and protein expression indicating
      a synergistic rather than an additive effect, not related to an increase of B(2)
      receptors density or its coupling. These potentiating effects of BK on PGE(2)
      production and increased COX-2 expression produced by IL-1beta were B(2)-receptor
      mediated as fasitibant could prevent them. None of the treatments induced changes
      in the COX-1 expression. The synergistic PGE(2) production was abolished by the
      specific NF-kappaB inhibitor (BAY-117085), whereas specific inhibitors for the
      p38 (SB203580), JNK (SP600125), and ERK1/2 (PD98059) mitogen-activated protein
      kinases could prevent the prostanoid release. BK can potentiate the COX-2 gene
      expression and consequent prostanoid production induced by IL-1beta. The
      prevention of this synergism by fasitibant indicates BK B(2) receptor blockade as
      an alternative symptomatic therapy for osteoarthritis.

PMID- 22638769
TI  - Breast cancer risk factors differ between Asian and white women with BRCA1/2
      mutations.
AB  - The prevalence and penetrance of BRCA1 and BRCA2 (BRCA1/2) mutations may differ
      between Asians and whites. We investigated BRCA1/2 mutations and cancer risk
      factors in a clinic-based sample. BRCA1/2 mutation carriers were enrolled from
      cancer genetics clinics in Hong Kong and California according to standardized
      entry criteria. We compared BRCA mutation position, cancer history, hormonal and
      reproductive exposures. We analyzed DNA samples for single-nucleotide
      polymorphisms reported to modify breast cancer risk. We performed logistic
      regression to identify independent predictors of breast cancer. Fifty Asian women
      and forty-nine white American women were enrolled. BRCA1 mutations were more
      common among whites (67 vs. 42 %, p = 0.02), and BRCA2 mutations among Asians (58
      vs. 37 %, p = 0.04). More Asians had breast cancer (76 vs. 53 %, p = 0.03); more
      whites had relatives with breast cancer (86 vs. 50 %, p = 0.0003). More whites
      than Asians had breastfed (71 vs. 42 %, p = 0.005), had high BMI (median 24.3 vs.
      21.2, p = 0.04), consumed alcohol (2 drinks/week vs. 0, p < 0.001), and had
      oophorectomy (61 vs. 34 %, p = 0.01). Asians had a higher frequency of risk
      associated alleles in MAP3K1 (88 vs. 59 %, p = 0.005) and TOX3/TNRC9 (88 vs. 55
      %, p = 0.0002). On logistic regression, MAP3K1 was associated with increased
      breast cancer risk for BRCA2, but not BRCA1 mutation carriers; breast density was
      associated with increased risk among Asians but not whites. We found significant
      differences in breast cancer risk factors between Asian and white BRCA1/2
      mutation carriers. Further investigation of racial differences in BRCA1/2
      mutation epidemiology could inform targeted cancer risk-reduction strategies.

PMID- 22638770
TI  - Analysis of a Finnish family confirms RHBDF2 mutations as the underlying factor
      in tylosis with esophageal cancer.
AB  - Tylosis with esophageal cancer (TOC) is a rare familial cancer syndrome inherited
      in an autosomal-dominant manner and characterized by esophageal cancer
      susceptibility and hyperkeratotic skin lesions. Two heterozygous missense
      mutations in the RHBDF2 gene were recently reported to be associated with TOC in
      three families: a p.Ile186Thr mutation was found in families from the UK and the
      US and a p.Pro189Leu mutation was detected in a German TOC family. We aimed to
      validate these novel results in an independent material by screening RHBDF2 in a
      previously unreported Finnish TOC family. We identified a new missense mutation,
      p.Asp188Asn, segregating with TOC in the Finnish family, and interestingly the
      detected mutation alters a codon located between the two previously reported
      mutation sites. Thus, we confirmed RHBDF2 mutations as the underlying cause of
      the TOC syndrome and our results suggest that the TOC associated mutations might
      be specific for this particular site in the RHBDF2 gene. These results enable the
      genetic counseling and diagnostic mutation screening of the members of TOC
      families.

PMID- 22638771
TI  - Visual acuity of dentists under simulated clinical conditions.
AB  - OBJECTIVES: This study examined the near visual acuity of dentists in relation to
      age and magnification under simulated clinical conditions. MATERIALS AND METHODS:
      Miniaturized visual tests were performed in posterior teeth of a dental phantom
      head in a simulated clinical setting (dental chair, operating lamp, dental
      mirror). The visual acuity of 40 dentists was measured under the following
      conditions: (1) natural visual acuity, distance of 300 mm; (2) natural visual
      acuity, free choice of distance; (3) Galilean loupes, magnification of *2.5; (4)
      Keplerian loupes, *4.3; (5) operating microscope, *4, integrated light; (6)
      operating microscope, *6.4, integrated light. RESULTS: The visual acuity varied
      widely between individuals and was significantly lower in the group >=40 years of
      age (p < 0.001). Significant differences were found between all tested conditions
      (p < 0.01). Furthermore, a correlation between visual acuity and age was found
      for all conditions. The performance with the microscope was better than with
      loupes even with comparable magnification factors. Some dentists had a better
      visual acuity without optical aids than others with Galilean loupes. CONCLUSIONS:
      Near visual acuity under simulated clinical conditions varies widely between
      individuals and decreases throughout life. Visual deficiencies can be compensated
      for with optical aids. CLINICAL RELEVANCE: Newly developed miniaturized vision
      tests have allowed, in a clinically relevant way, to evaluate the influence of
      magnification and age on the near visual acuity of dentists.

PMID- 22638772
TI  - Characterisation of bone following ultrasonic cutting.
AB  - OBJECTIVES: Ultrasonic surgery is an increasingly popular technique for cutting
      bone, but little research has investigated how the ultrasonic tip oscillations
      may affect the cuts they produce in bone. The aim of this investigation was to
      evaluate the oscillation and cutting characteristics of an ultrasonic surgical
      device. MATERIALS AND METHODS: A Piezosurgery 3 (Mectron, Carasco, Italy)
      ultrasonic cutting system was utilised with an OP3 style tip. The system was
      operated with the tip in contact with porcine bone samples (loads of 50 to 200 g)
      mounted at 45 degrees  to the vertical insert tip and with a water flow of 57
      ml/min. Tip oscillation amplitude was determined using scanning laser vibrometry.
      Bone surfaces defects were characterised using laser profilometry and scanning
      electron microscopy. RESULTS: A positive relationship was observed between the
      magnitude of tip oscillations and the dimensions of defects cut into the bone
      surface. Overloading the tip led to a reduction in oscillation and hence in the
      defect produced. A contact load of 150 g provided the greatest depth of cut.
      Defects produced in the bone came from two clear phases of cutting. CONCLUSIONS:
      The structure of the bone was found to be an important factor in the cut
      characteristics following piezosurgery. CLINICAL RELEVANCE: Cutting of bone with
      ultrasonics is influenced by the load applied and the setting used. Care must be
      used to prevent the tip from sliding over the bone at low loadings.

PMID- 22638773
TI  - The arrangement of the interproximal interfaces in the human permanent dentition.
AB  - OBJECTIVES: The interproximal interface (IPI) is the interface between two
      adjacent teeth, i.e., the site where forces are transmitted along the dental
      arch. We investigated the IPI arrangement of the human permanent dentition.
      Specifically, the IPI morphometrical characteristics were studied and interpreted
      within a biomechanical framework. SUBJECTS AND METHODS: A novel in vivo IPI
      measurement was developed based on diversity in transillumination of Polyvinyl
      siloxane impression of the interproximal region. The study group included 30
      subjects, aged 27, +/-4.0 years. Eleven parameters were examined in each of the
      26 IPIs of the permanent dentition. RESULTS: The IPI showed intra-arch similarity
      and interarch diversity between the tooth groups. The IPI shape was predominantly
      oval (60-100%), yet kidney-shaped in some molars (22-40%). From incisors to
      molars: the IPI increased significantly (p < 0.001) in size (1.72 to 6.05 mm(2)),
      occupied more of the proximal wall (7.8-12%), changed its orientation from
      vertical to horizontal (88.66-14.80 degrees ), and was mainly located in the
      buccal-occlusal quadrant of the proximal wall, chiefly in the molar teeth.
      CONCLUSIONS: The IPI is a product of proximal wall attrition and is dictated by
      the mastication forces, number of cusps, and crown inclination. IPI arrangement
      counteracts the adverse crowding effect of the anterior component of the
      mastication forces. CLINICAL RELEVANCE: The IPI characteristics found in the
      present study provide guidelines for crown and proximal filling restorations to
      meet dental physiology requirements. Further, IPI determines correct tooth
      alignment and proximal wall stripping applied to resolve arch length deficiency.

PMID- 22638774
TI  - [Culex quinquefasciatus sensitivity to insecticides in relation to the
      urbanization level and sewage water in Yopougon, a township of Abidjan (Cote
      d'Ivoire)].
AB  - This survey, conducted from July 2003 to June 2004, was to assess the variation
      of the level of sensitivity of Cx. quinquefasciatus to the pyrethroids
      recommended for the impregnation of the mosquito nets, in the township of
      Yopougon situated in the Northwest of Abidjan city in relation with the bed of a
      drainage channel of sewage water that passes through the township from the north
      to the south. Five districts have been chosen along this channel according to the
      level of urbanization, for the withdrawal of the pre-imaginal populations of Cx.
      quinquefasciatus in collections of stagnant sewage water of this township. The
      female Cx. quinquefasciatus aged three to five days from the exits of the
      insectarium have been exposed to papers impregnated with deltamethrin 0.05%,
      permethrin 1% and DDT 4% in view of the diagnosis of a possible resistance of
      these populations to these insecticides. The populations of Cx. quinquefasciatus
      proved to be resistant to the three insecticides used, in four districts. On the
      other hand, the population of Cx. quinquefasciatus from the district "Zone
      industrielle," situated upstream of the channel, proved to be sensitive to
      permethrin 1%, and a drastic decrease of sensitivity of the same mosquito has
      been observed with deltamethrin 0.05% and DDT 4%.

PMID- 22638775
TI  - Amyloid-beta protein modulates insulin signaling in presynaptic terminals.
AB  - Synaptic loss is a major neuropathological correlate of memory decline as a
      result of Alzheimer's disease (AD). This phenomenon appears to be aggravated by
      soluble amyloid-beta (Abeta) oligomers causing presynaptic terminals to be
      particularly vulnerable to damage. Furthermore, insulin is known to participate
      in synaptic plasticity through the activation of the insulin receptor (IR) and
      the PI3K signaling pathway, while low concentrations of soluble Abeta and Abeta
      oligomers aberrantly modulate IR function in cultured neurons. To further examine
      how Abeta and insulin interact in the pathology of AD, the present work analyzes
      the effect of insulin and Abeta in the activation of the IR/PI3K pathway in
      synaptosomes. We found that insulin increased mitochondrial activity and IR/Akt
      phosphorylation in synaptosomes taken from both hippocampus and cortex. Also,
      pretreatment with Abeta antagonized insulin's effect on hippocampal synaptosomes,
      but not vice versa. These results show that Abeta can reduce responsiveness to
      insulin. Combined with evidence that insulin desensitization can increase the
      risk of developing AD, our results suggest that the initial mechanism that
      impairs synaptic maintenance in AD might start with Abeta changes in insulin
      sensitivity.

PMID- 22638777
TI  - The rediscovery of endoscopic ultrasound (EUS) in gastric cancer staging.

PMID- 22638778
TI  - Endoscopic mucosal resection and endoscopic submucosal dissection for en bloc
      resection of superficial pharyngeal carcinomas.
AB  - BACKGROUND AND STUDY AIM: Endoscopic mucosal resection (EMR) and endoscopic
      submucosal dissection (ESD) are being used increasingly to treat superficial
      oropharyngeal and hypopharyngeal carcinomas. The aim of this study was to clarify
      whether ESD provided better results than EMR for en bloc and complete resection
      of superficial pharyngeal carcinomas. PATIENTS AND METHODS: A total of 76
      superficial pharyngeal carcinomas in 59 consecutively treated patients were
      included. Patients underwent either conventional EMR (using a transparent cap or
      strip biopsy) (n = 45 lesions) or ESD (n = 31 lesions) between October 2006 and
      January 2011. The rates of en bloc resection, complete resection (defined as en
      bloc resection with tumor-free margins), major complications, and local
      recurrence were evaluated retrospectively as the therapeutic outcomes. RESULTS:
      ESD yielded significantly higher rates of both en bloc and complete resection
      compared with EMR (en bloc 77.4 % [24/31] vs. 37.8 % [17/45], P = 0.0002;
      complete 54.8 % [17/31] vs. 28.9 % [13/45], P = 0.0379). ESD was more frequently
      complicated by severe laryngeal edema (4/21 [19.0 %] vs. 1/31 [3.2 %], P =
      0.1446) and was also more time-consuming (124.9 +/- 65.1 minutes vs. 57.2 +/-
      69.6 minutes; P = 0.0014). Local recurrence was observed more often after EMR
      than after ESD (3/45 [6.7 %] vs. 0/31 [0 %]), although this difference did not
      reach statistical significance (P = 0.2658). CONCLUSIONS: ESD appears to be a
      superior method of endoscopic resection of superficial pharyngeal carcinomas for
      achieving both en bloc and complete resection, although these benefits were also
      associated with a higher incidence of complications and a significantly longer
      procedure time. Large prospective studies are needed to compare ESD with
      conventional EMR for superficial pharyngeal carcinomas.

PMID- 22638776
TI  - Role of astrocytes in pain.
AB  - Over the last decade, a series of studies has demonstrated that glia in the
      central nervous system play roles in many aspects of neuronal functioning
      including pain processing. Peripheral tissue damage or inflammation initiates
      signals that alter the function of the glial cells (microglia and astrocytes in
      particular), which in turn release factors that regulate nociceptive neuronal
      excitability. Like immune cells, these glial cells not only react at sites of
      central and/or peripheral nervous system damage but also exert their action at
      remote sites from the focus of injury or disease. As well as extensive evidence
      of microglial involvement in various pain states, there is also documentation
      that astrocytes are involved, sometimes seemingly playing a more dominant role
      than microglia. The interactions between astrocytes, microglia and neurons are
      now recognized as fundamental mechanisms underlying acute and chronic pain
      states. This review focuses on recent advances in understanding of the role of
      astrocytes in pain states.

PMID- 22638779
TI  - Propofol sedation with bispectral index monitoring is useful for endoscopic
      submucosal dissection: a randomized prospective phase II clinical trial.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has become a
      standard treatment. However, the treatment time tends to be relatively long and
      insufflation and manipulation of the endoscope can increase pain and discomfort.
      We aimed to find an optimal method for sedation during ESD. PATIENTS AND METHODS:
      Patients scheduled to undergo ESD for early gastric cancer or adenoma were
      randomly assigned to sedation with midazolam or propofol, and consciousness level
      was evaluated by bispectral index (BIS) monitoring. Primary end points of
      effectiveness (three parameters) and secondary end points of safety during ESD
      and after return to the ward were compared between the groups. Study registration
      was in the UMIN Clinical Trial Registry (UMIN 000001497), and the institutional
      trial number was KDOG 0801. RESULTS: From June 2008 through June 2009, we
      enrolled 178 patients (90 midazolam, 88 propofol). Regarding safety after ESD,
      recovery was significantly better in the propofol group immediately after and at
      1 hour and 2 hours after return to the ward (P < 0.001). The number of patients
      who required a continuous supply of oxygen 2 hours after returning to the ward
      was significantly lower in the propofol group (midazolam 18; propofol 6; P =
      0.010). Though propofol seemed to be better for effectiveness and safety, there
      were no statistically significant differences for all three primary end points
      and the safety parameters (hypotension, hypoxia, bradycardia). CONCLUSIONS:
      Propofol with BIS monitoring improved recovery of patients after ESD, though this
      study was underpowered to prove the effectiveness and safety of propofol.

PMID- 22638780
TI  - Predictors for lymph node metastasis in T1 colorectal cancer.
AB  - BACKGROUND AND STUDY AIMS: It is critical that the risk of lymph node metastasis
      (LNM) is evaluated for determining the suitability of endoscopic resection for T1
      colorectal cancer (CRC). Reported risk factors for LNM in completely resected T1
      CRC are deep submucosal invasion, grade 3, angiolymphatic invasion, and budding.
      The aim of the present study was to identify the histopathologic factors
      associated with LNM in T1 CRC. PATIENTS AND METHODS: The study involved 435
      patients with T1 CRC treated by endoscopic or surgical resection between January
      2001 and April 2010 at the National Cancer Center, Korea. The 435 patients were
      classified into two groups - those undergoing surgical resection (n = 324) and
      those undergoing endoscopic resection (n = 111). In the surgically resected
      group, details regarding depth of submucosal invasion, angiolymphatic invasion,
      tumor grade, budding, and background adenoma (BGA) were evaluated with respect to
      presence or absence of LNM. In the endoscopically resected group, the results of
      follow-ups and additional salvage surgeries were studied. RESULTS: In the
      surgically resected group, LNM was detected in 42 patients (13.0 %). Grade 3,
      angiolymphatic invasion, budding, and the absence of BGA were identified as
      factors associated with LNM in univariate and multivariate analyses (P < 0.05).
      Among the 50 patients in the endoscopically resected group with high risk, three
      were diagnosed as being LNM-positive during the follow-up period. There was no
      LNM in the endoscopically resected group with low risk. CONCLUSIONS: Grade 3,
      angiolymphatic invasion, budding, and the absence of BGA are the risk factors
      that predict LNM in patients with T1 CRC. In cases where endoscopically resected
      T1 CRC has no risk factor, cautious follow-up could be recommended. However, if
      the tumor has any risk factor, additional surgical resection should be
      considered.

PMID- 22638781
TI  - Prospective experimental study of transrectal viscerotomy closure using transanal
      endoscopic suture vs. circular stapler: a step toward NOTES.
AB  - BACKGROUND AND STUDY AIM: Endoluminal full-thickness closure of the rectal wall
      is critical in emerging procedures including endoscopic submucosal dissection and
      transrectal natural orifice transluminal endoscopic surgery (NOTES). This study
      aimed to compare manual suture using the transanal endoscopic operation platform
      (TEO; Karl Storz, Tuttlingen, Germany) with the end-to-end anastomosis hemorrhoid
      circular stapler (EEA; Covidien, Dublin, Ireland) for closure of the rectal
      viscerotomy during transrectal NOTES segmental colectomy. MATERIALS AND METHODS:
      A total of 12 swine underwent transrectal hybrid NOTES partial colectomies.
      Animals were divided into two groups according to the viscerotomy closure
      technique: 1) TEO manual suture; 2) EEA circular stapler closure. RESULTS: Mean
      (+/- SD) viscerotomy closure time was 67.5 +/- 59.5 minutes and 31.5 +/- 19.6
      minutes for TEO and EEA, respectively. There was one conversion to laparoscopy in
      the TEO group and a misfiring in the EEA group that required a TEO salvage
      suture. There was one positive air-leak test in each group. Peritoneal fluid
      collected at the end of the procedure tested positive for bacterial contamination
      in all cases. A mild stenosis was present in 4 /6 viscerotomies (67 %) in the TEO
      group and in 1/6 (17 %) in the EEA group on endoscopic control. Inflammatory
      changes were mild in 3/5 (60 %) and 4/5 (80 %) viscerotomies in the TEO and EEA
      groups, respectively, whereas severe inflammation was found in 2/5 (TEO) and 1 /5
      (EEA). CONCLUSION: Transrectal viscerotomy closure using the EEA circular stapler
      technique is feasible, easy to perform, and histologically comparable to suture
      closure through a TEO platform. It may offer an attractive alternative for NOTES
      segmental colectomies and endoscopic resections.

PMID- 22638782
TI  - Lymph node characterization in vivo using endoscopic ultrasound spectrum analysis
      with electronic array echo endoscopes.
AB  - Our purpose was to demonstrate the use of radiofrequency spectral analysis to
      distinguish between benign and malignant lymph nodes with data obtained using
      electronic array echo endoscopes, as we have done previously using mechanical
      echo endoscopes. In a prospective study, images were obtained from eight patients
      with benign-appearing lymph nodes and 11 with malignant lymph nodes, as verified
      by fine-needle aspiration. Midband fit, slope, intercept, correlation
      coefficient, and root-mean-square (RMS) deviation from a linear regression of the
      calibrated power spectra were determined and compared between the groups.
      Significant differences were observable for mean midband fit, intercept, and RMS
      deviation (t test P < 0.05). For benign (n = 16) vs. malignant (n = 12) lymph
      nodes, midband fit and RMS deviation provided classification with 89 % accuracy
      and area under receiver operating characteristic (ROC) curve of 0.95 based on
      linear discriminant analysis. We concluded that the mean spectral parameters of
      the backscattered signals from electronic array echo endoscopy can provide a
      noninvasive method to quantitatively discriminate between benign and malignant
      lymph nodes.

PMID- 22638783
TI  - Locoregional mitomycin C injection for esophageal stricture after endoscopic
      submucosal dissection.
AB  - This prospective study aimed to evaluate the feasibility and safety of
      locoregional mitomycin C (MMC) injection to treat refractory esophageal
      strictures after endoscopic submucosal dissection (ESD) for superficial
      esophageal carcinoma. Patients with dysphagia and strictures that were refractory
      to repeated endoscopic balloon dilation (EBD) were eligible. After EBD, MMC was
      injected into the dilated site. Between June 2009 and August 2010, five patients
      were recruited. The treatment was performed once in two patients and twice in
      three patients with recurrent dysphagia or restenosis. In all patients, passing a
      standard endoscope through the site was easy and the dysphagia grade improved
      (grade 3->1 in 3 patients, grade 4->2 in 2 patients). No serious complications
      were noted. During the observation period of 4.8 months, neither recurrent
      dysphagia nor re-stricture appeared in any of the patients. The combination of
      locoregional MMC injections and EBD is feasible and safe for the treatment of
      esophageal strictures after ESD.Recently, endoscopic submucosal dissection (ESD)
      has been developed and accepted as a new endoscopic treatment for
      gastrointestinal tumors. ESD is a promising treatment for superficial esophageal
      carcinoma (SEC), and it has a reliable en bloc resection rate. However, the
      application of ESD for widespread lesions is challenging because of the high risk
      of the development of severe strictures, which lead to a low quality of life
      after ESD. Although endoscopic balloon dilation (EBD) is effective for benign
      strictures, it needs to be performed frequently until the dysphagia disappears 1.
      Mitomycin C (MMC), which is a chemotherapeutic agent derived from some
      Streptomyces species 2, reduces scar formation when topically applied to a
      surgical lesion. MMC has been applied to treat strictures in a variety of
      anatomical locations, including a variety of organs 3. The aim of this study was
      to prospectively evaluate both the feasibility and the safety of locoregional MMC
      injection therapy in patients with refractory esophageal strictures after ESD for
      SEC.

PMID- 22638784
TI  - Multimodal endoscopic therapy for multifocal intraepithelial neoplasia and
      superficial esophageal squamous cell carcinoma.

PMID- 22638785
TI  - A one-to-one training program would be valuable in learning how to perform
      esophageal endoscopic mucosal resection.

PMID- 22638787
TI  - Endoscopic vs. laparoscopic gastrojejunostomy for duodenal obstruction: a
      randomized study in a porcine model.

PMID- 22638789
TI  - Cell surface display of a beta-glucosidase employing the type V secretion system
      on ethanologenic Escherichia coli for the fermentation of cellobiose to ethanol.
AB  - We used the autodisplay system AIDA-I, which belongs to the type V secretion
      system (TVSS), to display the beta-glucosidase BglC from Thermobifida fusca on
      the outer membrane of the ethanologenic Escherichia coli strain MS04 (MG1655
      ?pflB, ?adhE, ?frdA, ?xylFGH, ?ldhA, PpflB::pdc (Zm)-adhB (Zm)). MS04 that was
      transformed with the plasmid pAIDABglCRHis showed cellobiase activity (171
      U/g(CDW)) and fermented 40 g/l cellobiose in mineral medium in 60 h with an
      ethanol yield of 81 % of the theoretical maximum. Whole-cell protease treatment,
      SDS-PAGE, and Western-blot analysis demonstrated that BglC was attached to the
      external surface of the outer membrane of MS04. When attached to the cells, BglC
      showed 93.3 % relative activity in the presence of 40 g/l ethanol and retained
      100 % of its activity following 2 days of incubation at 37  degrees C with the
      same ethanol concentration. This study shows the potential of the TVSS (AIDA-I)
      and BglC as tools for the production of lignocellulosic bio-commodities.

PMID- 22638790
TI  - Engineering of Rhodococcus cell catalysts for tolerance improvement by sigma
      factor mutation and active plasmid partition.
AB  - Tolerance to various stresses is a key phenotype for cell catalysts, which are
      used widely in bioproduction of diverse valuable chemicals. Using the Rhodococcus
      ruber TH strain, which exhibits high nitrile hydratase activity, as the target
      cell catalyst for acrylamide production, we established a method to improve cell
      tolerance by stably introducing global transcription perturbation. The sigma(70)
      gene (sigA) of R. ruber was cloned and randomly mutated. An R. ruber TH3/pNV
      sigA(M) library containing additional sigA mutants was constructed and used for
      survival selection. The TH3/M4N1-59 mutant was selected by
      acrylonitrile/acrylamide double stress and exhibited a 160 % extension of the
      half-life of nitrile hydratase upon exposure to 40 % acrylamide. A redesigned
      parDE(M) gene was introduced to Rhodococcus to accomplish stable inheritance of
      plasmids. A two-batch acrylonitrile hydration reaction was performed using the
      engineered cells as a catalyst. Compared to TH3, the acrylamide productivity of
      TH3/M4N1-59DE(M) catalysis increased by 27.8 and 37.5 % in the first and second
      bioreaction batches, respectively. These data suggest a novel method for
      increasing the bioconversion productivity of target chemicals through sigA
      mutation of the cell catalyst.

PMID- 22638791
TI  - Temporal analysis of xylose fermentation by Scheffersomyces stipitis using
      shotgun proteomics.
AB  - Proteomics and fermentation technology have begun to integrate to investigate
      fermentation organisms in bioprocess development. This is the first shotgun
      proteomics study employed to monitor the proteomes of Scheffersomyces stipitis
      during xylose fermentation under oxygen limitation. We identified 958
      nonredundant proteins and observed highly similar proteomes from exponential to
      early stationary phases. In analyzing the temporal proteome, we identified unique
      expression patterns in biological processes and metabolic pathways, including
      alternative respiration salicylhydroxamic acid  (SHAM) pathway, activation of
      glyoxylate cycle, expression of galactose enzymes, and secondary zinc-containing
      alcohol dehydrogenase and O-glycosyl hydrolases. We identified the expression of
      a putative, high-affinity xylose sugar transporter Xut1p, but low-affinity xylose
      transporters were absent. Throughout cell growth, housekeeping processes included
      oxidative phosphorylation, glycolysis, nonoxidative branch of the pentose
      phosphate pathway, gluconeogenesis, biosynthesis of amino acids and aminoacyl
      total RNA (tRNA), protein synthesis and proteolysis, fatty acid metabolism, and
      cell division. This study emphasized qualitative analysis and demonstrated that
      shotgun proteomics is capable of monitoring S. stipitis fermentation and
      identifying physiological states, such as nutrient deficiency.

PMID- 22638792
TI  - Sister Mary Joseph's Nodule as the First Sign of Pancreatic Carcinoma.

PMID- 22638798
TI  - A phase I study of bevacizumab, everolimus and panitumumab in advanced solid
      tumors.
AB  - PURPOSE: Preclinical data suggest concurrent inhibition of VEGF, mTOR and EGFR
      pathways may augment antitumor and antiangiogenic effects compared to inhibition
      of each pathway alone. This study evaluated the maximum tolerated
      dose/recommended phase II dose and safety and tolerability of bevacizumab,
      everolimus and panitumumab drug combination. METHODS: Subjects with advanced
      solid tumors received escalating doses of everolimus and flat dosing of
      panitumumab at 4.8 mg/kg and bevacizumab at 10 mg/kg every 2 weeks. Dose-limiting
      toxicities (DLTs) were assessed in cycle 1; toxicity evaluation was closely
      monitored throughout treatment. Treatment continued until disease progression or
      undesirable toxicity. RESULTS: Thirty-two subjects were evaluable for toxicity;
      31 subjects were evaluable for tumor response. DLTs were observed in cohorts with
      everolimus at 10 and 5 mg daily and included grade 3 mucositis, skin rash and
      thrombocytopenia. Therefore, everolimus was dose-reduced to 5 mg three times
      weekly, which improved the tolerability of the treatment regimen. Common adverse
      events were skin rash/pruritus (91 %), mucositis/stomatitis (75 %),
      hypomagnesemia (72 %), hypocalcemia (56 %) and hypokalemia (50 %). There were 3
      partial responses; an additional 10 subjects had stable disease >=6 months. Three
      subjects with ovarian cancer and one with endometrial cancer achieved prolonged
      disease control ranging from 11 to >40 months. CONCLUSIONS: The recommended phase
      II dose is everolimus at 5 mg three times weekly plus panitumumab at 4.8 mg/kg
      and bevacizumab at 10 mg/kg every 2 weeks. This dosing regimen has an acceptable
      safety and tolerability profile and appears to have moderate the clinical
      activity in refractory tumors.

PMID- 22638807
TI  - Differences in autophagy-related activity by molecular subtype in triple-negative
      breast cancer.
AB  - The aim of this study was to assess the expression of significant components of
      autophagy including beclin-1, light chain (LC) 3A, LC3B, and p62 in the molecular
      subtypes of triple-negative breast cancer (TNBC) and to evaluate the implications
      of the results. Tissues from 119 cases of TNBC were used for a tissue microarray.
      Expression of cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR),
      claudin 3, claudin 4, claudin7, E-cadherin, androgen receptor (AR), and gamma
      glutamyltransferase 1 (GGT-1) was detected by immunohistochemical staining of the
      tissue microarrays. According to the results, the 119 cases of TNBC were
      subclassified into basal-like type (CK5/6-positive and/or EGFR-positive group),
      molecular apocrine type (AR-positive and/or GGT-1-positive group), claudin low
      type (claudin 3-, claudin 4-, or claudin 7-negative and/or E-cadherin-negative
      group), mixed type (having the features of more than two types), or null type
      (none of the above). Immunohistochemical staining for autophagy-related markers
      including beclin-1, LC3A, LC3B, and p62 was performed to evaluate the difference
      between clinicopathological parameters. TNBCs were categorized as basal-like type
      (36 patients, 30.3 %), molecular apocrine type (8 patients, 6.7 %), claudin low
      type (16 patients, 13.4 %), mixed type (37 patients, 31.1 %), and null type (22
      patients, 18.5 %). Expression of nuclear p62 was higher in the molecular apocrine
      type and claudin low type than in other types of TNBC (p = 0.008). Expression of
      beclin-1 was higher in molecular apocrine type than in other TNBC types (p =
      0.039). Expression of LC3A and LC3B showed no difference between the molecular
      subtypes. Multivariate Cox analysis revealed that the negative expression of p62
      was associated with shorter disease-free survival [p = 0.012; odds ratio, 3.192;
      95 % confidence interval (CI), 1.293-7.882] and shorter overall survival (p =
      0.009; odds ratio, 3.895; 95 % CI, 1.409-10.771). Among the subtypes of TNBC,
      molecular apocrine breast cancer showed a higher expression of nuclear p62 and
      beclin-1 than others, which reflected higher autophagy activity.

PMID- 22638811
TI  - Effects of d-amphetamine on simulated driving performance before and after sleep
      deprivation.
AB  - RATIONALE: Stimulant drugs are commonly abused and also used to promote
      wakefulness, yet their effects on driving performance during sleep deprivation
      have not been thoroughly researched in experimental studies. OBJECTIVES: The aims
      were to assess the effects on fundamental driving parameters during simulated
      driving of two doses of d-amphetamine and further to assess the interaction
      between d-amphetamine and sleep deprivation. METHODS: A double-blind, placebo
      controlled experiment including 18 healthy male volunteers was conducted.
      RESULTS: The participants felt more alert when taking a dose of d-amphetamine
      than when taking placebo, and the effect was stronger for the higher dose.
      However, the data did not show any evidence that taking d-amphetamine prevented
      the subjects from becoming successively sleepier during the night. A significant
      main effect of the dose was found for three out of the five primary indicators
      where the lower dose led to improved driving. These indicators were crossing-car
      reaction time, and coherence and delay from a car-following event. Regarding
      sleep deprivation, a main effect was found for four of the primary indicators and
      three of the secondary indicators. The results showed overall impaired driving
      with respect to standard deviation of lateral position and delay in reaction time
      when the sleep-deprived conditions were compared to the alert condition. We found
      no interactions between dose and sleep deprivation for any of the performance
      indicators. CONCLUSIONS: Our results suggest that administration of d-amphetamine
      does not compensate for impairment of driving due to fatigue. The positive
      effects of 10 mg were not further improved or even sustained when increasing the
      dose to 40 mg.

PMID- 22638812
TI  - The role of impulsivity and perceived availability on cue-elicited craving for
      alcohol in social drinkers.
AB  - RATIONALE: Previous research has demonstrated a role for impulsivity and
      perceived availability of the substance in cue-elicited craving. However, their
      effects on cue-elicited craving for alcohol are still ambiguous. Most important
      is that there has been no empirical evidence for the potential interaction of
      these factors on alcohol craving. OBJECTIVES: The aim of the present study was to
      examine the effects of response inhibition and perceived availability on cue
      elicited craving for alcohol in social drinkers. METHODS: Participants were light
      to moderate social drinkers (N = 75) who were exposed to neutral- and alcohol
      related stimuli during a single laboratory session. Response inhibition was
      assessed with the Stop Signal Task. Participants were randomly assigned to one of
      two perceived availability groups (n = 37, expecting alcohol; n = 38, not
      expecting alcohol). RESULTS: Overall craving for alcohol was higher in
      participants who expected alcohol than in those who did not. This finding was
      statistically significant only in the alcohol condition. Most important is that
      there was a significant interaction between response inhibition, perceived
      availability and time on cue-elicited craving. Regardless of the cue type,
      impulsive people who expected alcohol experience a significant increase in cue
      elicited craving relative to impulsive people who did not expect alcohol. This
      effect was not observed in the non-impulsive groups. CONCLUSIONS: The results
      clearly show that perceived availability alone and in combination with response
      inhibition can modulate alcohol cue reactivity. Theoretical explanations and
      clinical implications of these findings are discussed.

PMID- 22638813
TI  - The effect of VMAT2 inhibitor GZ-793A on the reinstatement of methamphetamine
      seeking in rats.
AB  - RATIONALE: The vesicular monoamine transporter 2 (VMAT2) has been identified as a
      potential target for the treatment of methamphetamine (METH) abuse. GZ-793A is a
      potent and selective VMAT2 inhibitor that has been shown to block the primary and
      conditioned reinforcing effects of METH, while demonstrating no abuse liability
      when given alone. OBJECTIVES: The aim of the current study was to determine if GZ
      793A attenuates METH- or cue-induced reinstatement of METH-seeking after a period
      of extinction. The effect of acute GZ-793A on locomotor activity also was
      assessed. METHODS: After a period of extinction, rats were administered GZ-793A
      (15 mg/kg, s.c.) 15 min prior to a priming injection of METH or re-exposure to
      cues associated with METH infusions. GZ-793A also was administered 20 min prior
      to an injection of METH (0.5 mg/kg, s.c.) or saline to determine its effect on
      locomotor behavior. RESULTS: Pretreatment with GZ-793A (15 mg/kg) decreased cue
      induced reinstatement, without demonstrating any response suppressive effects
      when administered in the absence of reinstating stimuli. GZ-793A also decreased
      methamphetamine-induced reinstatement; however, response suppressant effects of
      GZ-793A were obtained when the compound was presented alone. In this latter
      experiment, GZ-793A may have reduced responding for the conditioned reinforcing
      effects of the contingently available cues rather than having nonspecific effects
      on baseline responding. GZ-793A had no effect on locomotor activity when
      administered alone or with METH. CONCLUSIONS: GZ-793A and related VMAT2
      inhibitors may be promising leads for reducing the risk of relapse to METH use
      following exposure to drug-associated cues.

PMID- 22638825
TI  - Localization of neurones expressing the gap junction protein Connexin45 within
      the adult spinal dorsal horn: a study using Cx45-eGFP reporter mice.
AB  - Connexin (Cx) proteins localized to neuronal and glial syncytia provide the
      ultrastructural components for intercellular communication via gap junctions. In
      this study, a Cx45 reporter mouse model in which the Cx45 coding sequence is
      substituted for enhanced green fluorescent protein (eGFP) was used to
      characterize Cx45 expressing neurones within adult mouse spinal cord. eGFP
      immunoreactive (eGFP-IR) cells were localized at all rostro-caudal levels to
      laminae I-III of the dorsal horn (DH), areas associated with nociception. The
      neuronal rather than glial phenotype of these cells in DH was confirmed by co
      localisation of eGFP-IR with the neuronal marker NeuN. Further
      immunohistochemical studies revealed that eGFP-IR interneurones co-express the
      calcium-binding protein calbindin, and to a lesser extent calretinin. In
      contrast, eGFP-IR profiles did not co-localize with either parvalbumin or GAD-67,
      both of which are linked to inhibitory interneurones. Staining with the primary
      afferent markers isolectin-B4 (IB4) and calcitonin gene-related peptide revealed
      that eGFP-IR somata within laminae I-III receive close appositions from the
      former, presumed non-peptidergic nociceptive afferents of peripheral origin. The
      presence of 5-HT terminals in close apposition to eGFP-IR interneuronal somata
      suggests modulation via descending pathways. These data demonstrate a highly
      localized expression of Cx45 in a population of interneurones within the mouse
      superficial dorsal horn. The implications of these data in the context of the
      putative role of Cx45 and gap junctions in spinal somatosensory processing and
      pain are discussed.

PMID- 22638826
TI  - Variability of individual genetic load: consequences for the detection of
      inbreeding depression.
AB  - Inbreeding depression is a key factor affecting the persistence of natural
      populations, particularly when they are fragmented. In species with mixed mating
      systems, inbreeding depression can be estimated at the population level by
      regressing the average progeny fitness by the selfing rate of their mothers. We
      applied this method using simulated populations to investigate how population
      genetic parameters can affect the detection power of inbreeding depression. We
      simulated individual selfing rates and genetic loads from which we computed
      fitness values. The regression method yielded high statistical power, inbreeding
      depression being detected as significant (5 % level) in 92 % of the simulations.
      High individual variation in selfing rate and high mean genetic load led to
      better detection of inbreeding depression while high among-individual variation
      in genetic load made it more difficult to detect inbreeding depression. For a
      constant sampling effort, increasing the number of progenies while decreasing the
      number of individuals per progeny enhanced the detection power of inbreeding
      depression. We discuss the implication of among-mother variability of genetic
      load and selfing rate on inbreeding depression studies.

PMID- 22638814
TI  - Learning to forget: manipulating extinction and reconsolidation processes to
      treat addiction.
AB  - Finding effective long-lasting treatments for drug addiction has been an elusive
      goal. Consequently, researchers are beginning to investigate novel treatment
      strategies including manipulations of drug-associated memories. When
      environmental stimuli (cues) become associated with drug use, they become
      powerful motivators of continued drug use and relapse after abstinence. Reducing
      the strength of these cue-drug memories could decrease the number of factors that
      induce craving and relapse to aid in the treatment of addiction. Enhancing the
      consolidation of extinction learning and/or disrupting cue-drug memory
      reconsolidation are two strategies that have been proposed to reduce the strength
      of cues in motivating drug-seeking and drug-taking behavior. Here, we review the
      latest basic and clinical research elucidating the mechanisms underlying
      consolidation of extinction and reconsolidation of cue-drug memories in the hopes
      of developing pharmacological tools that exploit these signaling systems to treat
      addiction.

PMID- 22638827
TI  - Interspecific sexual isolation and phylogeny among different members of the
      Drosophila bipectinata species complex.
AB  - The degree and pattern of sexual isolation among closely related species can be
      utilized for predicting the direction of evolution and deriving a phylogeny. The
      Drosophila bipectinata species complex is a group of four morphologically very
      similar species, belonging to the ananassae subgroup of the melanogaster species
      group. Sexual isolation among the members of this complex was studied by
      employing the male-choice technique. To test the difference between the homogamic
      and heterogamic matings, chi-square values were calculated under the assumption
      of random mating and the degree of sexual isolation was measured by estimating
      isolation index. To test the difference in proportions of heterogamic matings
      between reciprocal crosses, normal deviate (z) was calculated. The direction of
      evolution among these species has been discussed in the light of models proposed
      by different workers. Our results suggest that while D. bipectinata, Drosophila
      parabipectinata and Drosophila malerkotliana are closely related to each other,
      D. pseudoananassae is distantly related to these three species. The species pairs
      D. bipectinata and D. parabipectinata and D. parabipectinata and D. malerkotliana
      show asymmetrical sexual isolation. Based on this, it is suggested that D.
      bipectinata and D. malerkotliana share a common ancestor where as D.
      parabipectinata has been derived from D. bipectinata. Their phylogenetic
      relationship has been discussed in the light of phylogenies suggested by earlier
      workers.

PMID- 22638833
TI  - beta2 Adrenoceptor signaling-induced muscle hypertrophy from blood flow
      restriction: is there evidence?
AB  - Skeletal muscle hypertrophy and increases in muscular function have been observed
      following low intensity/load exercise with blood flow restriction (BFR). The
      mechanisms behind these effects are largely unknown, but have been hypothesized
      to include a metabolic accumulation induced increase in muscle activation,
      elevations in growth hormone, and improvements in muscle protein balance.
      However, many of the aforementioned mechanisms are not present with BFR in the
      absence of exercise. In these situations, signaling through the beta2
      adrenoceptor has been hypothesized to possibly contribute to the positive muscle
      adaptions, possibly in concert with muscle cell swelling. Signaling through the
      beta2 adrenoceptor has been shown to stimulate both muscle protein synthesis and
      an inhibition of protein degradation through increasing cyclic adenosine
      monophosphate (cAMP) or signaling via the Gbetagamma subunit, especially in
      situations where the basal rates of protein synthesis are already reduced. Every
      study that has investigated the catecholamine response to BFR in the absence of
      exercise or in combination with exercise has shown a significant increase above
      resting conditions. However, from the available evidence, it is unlikely that the
      norepinephrine response from BFR, particularly with exercise, is playing a
      prominent role with muscle adaptation in skeletal muscle that is not immobilized
      by a cast or joint injury.

PMID- 22638834
TI  - Developmental plasticity in thyroid function primed by maternal hyperleptinemia
      in early lactation: a time-course study in rats.
AB  - Pups whose mothers were leptin-treated during the last 3 days of lactation have
      thyroid dysfunction at adulthood. However, there was no report about leptin
      treatment in the first days of life or about its action on thyroid function
      during development. Here, we evaluated the effects of maternal leptin treatment
      on the first 10 days of lactation upon thyroid function of the offspring at 21,
      30, and 180 days old. At birth, lactating Wistar rats were divided into: Leptin
      (Lep) - leptin-treated (8 MUg/100 g of body weight, s.c.) for the first 10 days
      of lactation and Control (C, saline-treated). Mothers were killed at the end of
      lactation and their offspring at 21, 30, and 180 days old. Triiodothyronine (T3),
      thyroxine (T4), thyrotropin (TSH), and leptin levels in serum and milk were
      measured. Liver mitochondrial glycerolphosphate dehydrogenase (mGPD) activity was
      determined. Significant differences had p<0.05. At the end of lactation, Lep
      mothers had higher milk T3 (+ 30%), while their offspring had higher serum T3 (+
      20%) and TSH (+ 84%). At 30 days-old, Lep offspring showed lower TSH ( - 48%), T3
      ( - 20%), and mGPDm ( - 42%). At 180 days-old, Lep group presented
      hyperleptinemia (1.4-fold increase), higher serum T3 (+ 22%), and lower mGPD
      activity ( - 57%). Maternal hyperleptinemia on lactation causes hypothyroidism in
      the pups at 30 days, which may program for higher serum T3 at adulthood. In
      conclusion, maternal hyperleptinemia during lactation, that is common in obese
      mothers, may have an impact in future disease development, such as thyroid
      dysfunction.

PMID- 22638835
TI  - Regulation of electrolyte and fluid metabolism in multi-stage ultra-marathoners.
AB  - The purposes of this study were (i) to determine the prevalence of exercise
      associated hyponatremia (EAH) in multi-stage ultra-marathoners and (ii) to gain
      more insight into fluid and electrolyte regulation during a multi-stage race.
      Body mass, sodium concentration ([Na+]), potassium concentration ([K+]),
      creatinine, urea, specific gravity, and osmolality in urine were measured in 25
      male ultra-marathoners in the 'Swiss Jura Marathon' 2008 with 11,000 m gain of
      altitude over 7 stages covering 350 km, before and after each stage. Haemoglobin,
      haematocrit, creatinine, urea, [Na+], [K+], and osmolality were measured in
      plasma before stage 1 and after stages 1, 3, 5, and 7. Two athletes (8%) showed
      plasma [Na+] <135 mmol/l. Body mass, plasma [Na+], and plasma [K+] remained
      unchanged (p>0.05). Urine specific gravity (p<0.001) and osmolality in both
      plasma (p<0.01) and urine (p<0.001) were increased and haematocrit (p<0.0001),
      haemoglobin (p<0.0001) and plasma albumin were decreased (p<0.001). Plasma volume
      (p<0.01) and plasma urea (p<0.001) were increased. The K+/Na+ ratio in urine
      increased >1.0 after each stage and returned to <1.0 the morning of the next
      stage (p<0.001). To summarize, more sodium than potassium was excreted during
      rest. The increased urinary sodium losses during rest are compatible with the
      syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or the
      cerebral salt-wasting syndrome (CSWS). Further studies are needed to determine
      the antidiuretic hormone (ADH) and both the atrial natriuretic peptide (ANP) and
      the brain natriuretic peptide (BNP) during multi-stage races.

PMID- 22638836
TI  - The 2009 pandemic influenza virus: where did it come from, where is it now, and
      where is it going?
AB  - Around 2008 or 2009, an influenza A virus that had been circulating undetected in
      swine entered human population. Unlike most swine influenza infections of humans,
      this virus established sustained human-to-human transmission, leading to a global
      pandemic. The virus responsible, 2009 pandemic H1N1 (H1N1pdm), is the result of
      multiple reassortment events that brought together genomic segments from
      classical H1N1 swine influenza virus, human seasonal H3N2 influenza virus, North
      American avian influenza virus, and Eurasian avian-origin swine influenza
      viruses. Genetically, H1N1pdm possesses a number of unusual features, although
      the genomic characteristics that permitted sustained human-to-human transmission
      are yet unclear. Human infection with H1N1pdm has generally resulted in low
      mortality, although certain subgroups (including pregnant women, people with some
      chronic medical conditions, morbidly obese individuals, and immunosuppressed
      people) have significantly higher risk of severe disease. As H1N1pdm has spread
      throughout the human population it continued to evolve. It has also reentered the
      swine population as a circulating pathogen, and has been transiently identified
      in other species such as turkeys, cats, and domestic ferrets. Most genetic
      changes in H1N1pdm to date have not been clearly linked to changes in
      antigenicity, disease severity, antiviral drug resistance, or transmission
      efficiency. However, the rapid evolution rate characteristic of influenza viruses
      suggests that changes in antigenicity are inevitable in future years. Experience
      with this first pandemic of twenty-first century reemphasizes the importance of
      influenza surveillance in animals as well as humans, and offers lessons to
      develop and enhance our ability to identify potentially pandemic influenza
      viruses in the future.

PMID- 22638837
TI  - Enhanced photocatalytic performance of ZnS for reversible amination of alpha-oxo
      acids by hydrothermal treatment.
AB  - To understand how life could have originated on early Earth, it is essential to
      know what biomolecules and metabolic pathways are shared by extant organisms and
      what organic compounds and their chemical reaction channels were likely to have
      been primordially available during the initial phase of the formation of
      prebiotic metabolism. In a previous study, we demonstrated for the first time the
      reversible amination of alpha-oxo acids on the surface of photo-illuminated ZnS.
      The sulfide mineral is a typical component at the periphery of submarine
      hydrothermal vents which has been frequently argued as a very attractive venue
      for the origin of life. In this work, in order to simulate more closely the
      precipitation environments of ZnS in the vent systems, we treated newly
      precipitated ZnS with hydrothermal conditions and found that its photocatalytic
      power was significantly enhanced because the relative crystallinity of the
      treated sample was markedly increased with increasing temperature. Since the
      reported experimental conditions are believed to have been prevalent in shallow
      water hydrothermal vents of early Earth and the reversible amination of alpha-oxo
      acids is a key metabolic pathway in all extant life forms, the results of this
      work provide a prototypical model of the prebiotic amino acid redox metabolism.
      The amino acid dehydrogenase-like chemistry on photo-irradiated ZnS surfaces may
      advance our understanding of the establishment of archaic non-enzymatic metabolic
      systems.

PMID- 22638838
TI  - Plasmid stability in dried cells of the desert cyanobacterium Chroococcidiopsis
      and its potential for GFP imaging of survivors on Earth and in space.
AB  - Two GFP-based plasmids, namely pTTQ18-GFP-pDU1(mini) and pDUCA7-GFP, of about 7
      kbp and 15 kbp respectively, able to replicate in Chroococcidiopsis sp. CCMEE 029
      and CCMEE 123, were developed. Both plasmids were maintained in Chroococcidiopsis
      cells after 18 months of dry storage as demonstrated by colony PCR, plasmid
      restriction analysis, GFP imaging and colony-forming ability under selection of
      dried transformants; thus suggesting that strategies employed by this
      cyanobacterium to stabilize dried chromosomal DNA, must have protected plasmid
      DNA. The suitability of pDU1(mini)-plasmid for GFP tagging in Chroococcidiopsis
      was investigated by using the RecA homolog of Synechocystis sp. PCC 6803. After 2
      months of dry storage, the presence of dried cells with a GFP-RecA(Syn)
      distribution resembling that of hydrated cells, supported its capability of
      preventing desiccation-induced genome damage, whereas the rewetted cells with
      filamentous GFP-RecA(Syn) structures revealed sub-lethal DNA damage. The long
      term stability of plasmid DNA in dried Chroococcidiopsis has implication for
      space research, for example when investigating the recovery of dried cells after
      Martian and space simulations or when developing life support systems based on
      phototrophs with genetically enhanced stress tolerance and stored in the dry
      state for prolonged periods.

PMID- 22638839
TI  - Widen the belt of habitability!
AB  - Among the key-parameters to characterize habitability are presence or
      availability of liquid water, an appropriate temperature range, and the time
      scale of reference. These criteria for habitability are discussed and described
      from the point of view of water- and ice-physics, and it is shown that liquid
      water may exist in the sub-surfaces of planetary bodies like Mars, and possibly
      of inner asteroids and internally heated ice-moons. Water can remain fluid there
      also at temperatures far below the "canonical" 0  degrees C. This behaviour is
      made possible as a consequence of the freezing point depression due to salty
      solutes in water or "brines", as they can be expected to exist in nature more
      frequently than pure liquid water. On the other hand, low temperatures cause a
      slowing down of chemical processes, as can be described by Arrhenius's relation.
      The resulting smaller reaction rates probably will have the consequence to
      complicate the detection of low-temperature life processes, if they exist.
      Furthermore, the adaptation potential of life is to be mentioned in this context
      as a yet partially unknown process. Resulting recommendations are given to
      improve the use of criteria to characterize habitable conditions.

PMID- 22638840
TI  - A cultural and social cognitive model of differences in acculturation
      orientations, alcohol expectancies, and alcohol-related risk behaviors among
      Hispanic college students.
AB  - OBJECTIVES: The present study used a cultural and social cognitive conceptual
      framework to investigate whether alcohol expectancies and valuations would
      mediate the associations between specific acculturation orientations and alcohol
      related risk behaviors. DESIGN: The sample comprised 1,527 Hispanic students
      attending colleges and universities in diverse regions of the United States.
      Respondents completed self-report measures of Hispanic and American cultural
      practices; alcohol expectancies and valuations; and self-reported frequency of
      hazardous alcohol use, binge drinking, sexual activity under the influence of
      alcohol, driving under the influence of alcohol, and riding with a drunk driver.
      Latent class analysis was used to classify participants into acculturation
      orientations. RESULTS: Results indicated that acculturation orientations were
      differentially associated with alcohol-related risk outcomes, with separated
      bicultural and low bicultural orientations inversely related to all of the
      alcohol-related risk behaviors except for riding with a drunk driver. Negative
      expectancy valuations were positively associated with endorsement of binge
      drinking and drunk driving and negative expectancies were negatively associated
      with binge drinking, drunk driving, and riding with a drunk driver. With the
      exception of sexual activity under the influence of alcohol, the associations
      between acculturation orientations and alcohol-related risk behaviors were
      partially mediated by positive alcohol expectancies. CONCLUSIONS: Our findings
      provided relevant data that are informative for preventing alcohol and related
      risk behaviors among Hispanic college students.

PMID- 22638841
TI  - Chronic urticaria.
AB  - Chronic urticaria is defined as case of spontaneous wheals and/or angioedema
      persisting for a period of at least six weeks. The disease has an average
      duration of three to five years and is strongly associated with a decrease of
      quality of life and performance. Current international guidelines recommend the
      use of non-sedating antihistamines as the first choice in therapy and up-dosing
      these up to fourfold in cases of non-response. Alternative treatments for the
      afflicted who do not respond to antihistamine-treatment are also available but
      are not approved for use on urticaria.

PMID- 22638842
TI  - Amplification of oral streptococcal DNA from human incisors and bite marks.
AB  - Challenges to the evidentiary value of morphometric determinations have led to a
      requirement for scientifically substantiated approaches to the forensic analysis
      of bite marks. Human teeth support genotypically distinctive populations of
      bacteria that could be exploited for forensic purposes. This study explored the
      feasibility of directly amplifying bacterial DNA from bite marks for comparison
      with that from teeth. Samples from self-inflicted experimental bite marks (n =
      24) and human incisors were amplified by PCR using primers specific for
      streptococcal 16S ribosomal DNA. Amplicon profiles (resolved by denaturing
      gradient gel electrophoresis) from bite mark samples aligned significantly more
      closely with profiles generated from the teeth responsible than with those from
      other teeth. Streptococcal amplicons were generated from dental samples applied
      to excised porcine skin for up to 48 h. These findings indicate that
      streptococcal DNA can be amplified directly from bite marks, and have potential
      application in bite mark analysis.

PMID- 22638843
TI  - Arsenite oxidation in Ancylobacter dichloromethanicus As3-1b strain: detection of
      genes involved in arsenite oxidation and CO2 fixation.
AB  - The aim of this study was to characterize a facultative chemolithotrophic
      arsenite-oxidizing bacterium by evaluating the growth and the rate of arsenite
      oxidation and to investigate the genetic determinants for arsenic resistance and
      CO(2) fixation. The strain under study, Ancylobacter dichloromethanicus As3-1b,
      in a minimal medium containing 3 mM of arsenite as electron donor and 6 mM of
      CO(2)-bicarbonate as the C source, has a doubling time (t(d)) of 8.1 h. Growth
      and arsenite oxidation were significantly enhanced by the presence of 0.01 %
      yeast extract, decreasing the t(d) to 4.3 h. The strain carried arsenite oxidase
      (aioA) gene highly similar to those of previously reported arsenite-oxidizing
      Alpha-proteobacteria. The RuBisCO Type-I (cbbL) gene was amplified and sequenced
      too, underscoring the ability of As3-1b to carry out autotrophic As(III)
      oxidation. The results suggest that A. dichloromethanicus As3-1b can be a good
      candidate for the oxidation of arsenite in polluted waters or groundwaters.

PMID- 22638844
TI  - Limited sampling strategy models for estimating the AUC of gliclazide in Chinese
      healthy volunteers.
AB  - The aim of this work is to reduce the cost of required sampling for the
      estimation of the area under the gliclazide plasma concentration versus time
      curve within 60 h (AUC0-60t ). The limited sampling strategy (LSS) models were
      established and validated by the multiple regression model within 4 or fewer
      gliclazide concentration values. Absolute prediction error (APE), root of mean
      square error (RMSE) and visual prediction check were used as criterion. The
      results of Jack-Knife validation showed that 10 (25.0 %) of the 40 LSS based on
      the regression analysis were not within an APE of 15 % using one concentration
      time point. 90.2, 91.5 and 92.4 % of the 40 LSS models were capable of prediction
      using 2, 3 and 4 points, respectively. Limited sampling strategies were developed
      and validated for estimating AUC0-60t of gliclazide. This study indicates that
      the implementation of an 80 mg dosage regimen enabled accurate predictions of
      AUC0-60t by the LSS model. This study shows that 12, 6, 4, 2 h after
      administration are the key sampling times. The combination of (12, 2 h), (12, 8,
      2 h) or (12, 8, 4, 2 h) can be chosen as sampling hours for predicting AUC0-60t
      in practical application according to requirement.

PMID- 22638855
TI  - Neuroplastin expression in the hippocampus of mice lacking complex gangliosides.
AB  - We report changes in neuroplastin gene and protein expression in the hippocampus
      of B4galnt1 null mice, which lacks complex ganglioside structures, compared with
      that of wild-type mice. Neuroplastin mRNA expression was significantly higher in
      the hippocampi of B4galnt1 null mice than in wild-type mice. Moreover, Western
      blot analysis shows increased neuroplastin protein levels of neuroplastin-55
      isoform in B4galnt1 null hippocampal homogenates. Immunohistochemistry revealed a
      substantially different distribution of neuroplastin immunoreactivity in sagittal
      sections of the hippocampi derived from B4galnt1 null in comparison with those
      from wild-type mice. Most strikingly, B4galnt1 null mice had relatively little
      neuroplastin immunoreactivity in the pyramidal layer of CA1 and CA3, whereas wild
      type mice had strong neuroplastin staining of pyramidal cells. Results of this
      study support the hypothesis that alterations of brain ganglioside expression
      influence the expression of neuroplastin. As both neuroplastin and gangliosides
      have important roles in synaptic transmission, synaptic plasticity, and neurite
      outgrowth, it will be of particular interest to unravel the molecular mechanisms
      underlying the relationship between ganglioside composition and neuroplastin
      transcript and protein expression in the mammalian nervous system.

PMID- 22638856
TI  - Transplantation of placenta-derived mesenchymal stem cells in the EAE mouse model
      of MS.
AB  - Stem cell-based regenerative medicine raises great hope for the treatment of
      multiple sclerosis (MS). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are
      being tested in clinical trials. Bone marrow is the traditional source of human
      MSCs, but human term placenta appears to be an excellent alternative because of
      its availability, without ethical issues. In this study, the therapeutic effect
      of human placental MSCs (PL-MSCs) was evaluated in experimental autoimmune
      encephalomyelitis (EAE), the mice model of MS. EAE mice were transplanted intra
      cerebrally with PL-MSCs or with the vehicle saline 5 or 10 days after first MOG
      injection. The mice were monitored for a month after therapy. A daily EAE score
      revealed a decrease in disease severity in the transplanted animals when compared
      to saline. Survival was significantly higher in the transplanted animals. In
      vitro experiments demonstrated that conditioned media from LPS-activated
      astrocytes stimulated PL-MSCs to express the gene TNF-alpha-stimulated
      gene/protein 6 (TSG-6). The same mRNA expression was obtained when PL-MSCs were
      exposed to TNF-alpha or IL1-beta. These results demonstrate that PL-MSCs have a
      therapeutic effect in the EAE mice model. We assume that this effect is caused by
      reduction of the anti-inflammatory protein, TSG-6, of the inflammatory damage.

PMID- 22638857
TI  - Effects of pituitary adenylate cyclase activating polypeptide on human sperm
      motility.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP), a neuropeptide with
      diverse effects, was originally isolated as a hypothalamo-hypophyseal peptide.
      Subsequent studies showed highest levels of PACAP in the testis after the brain,
      suggesting that it influences the development and functioning of spermatozoa.
      Indeed, it has been proven that PACAP has an effect on spermatogenesis, both
      locally and via influencing the hypothalamo-hypophyseal-gonadal axis. The aim of
      the present study was to determine whether PACAP has an effect on human sperm
      motility and whether it is present in the human seminal fluid. Furthermore, the
      sperm head morphology was studied in mice lacking endogenous PACAP. Human samples
      were obtained from healthy adult volunteers and andrological patients. The
      effects of PACAP on the motility of human sperm cells were investigated using a
      computer aided sperm analysis system. In cases where the motility was lower,
      addition of PACAP to the samples increased the motility and the ratio of rapid
      progressive and medium progressive sperm motility groups. The presence of PACAP
      could not be detected in human seminal fluid samples by means of mass
      spectrometry. Investigating sperm head morphology with routine histology in PACAP
      deficient mice revealed that both the longitudinal and transverse diameters were
      significantly lower in PACAP deficient mice, without marked difference in the
      shape, as revealed by scanning electron microscopy.

PMID- 22638858
TI  - Apelin-13 protects the brain against ischemic reperfusion injury and cerebral
      edema in a transient model of focal cerebral ischemia.
AB  - The adipocytokine apelin is a peptide that was isolated from a bovine stomach for
      the first time. This peptide and its receptor are abundantly expressed in the
      nervous and cardiovascular systems. According to previous studies, apelin-13
      protects cardiomyocytes from ischemic injury as well as apoptosis. In addition,
      this peptide has a neuroprotective effect on hippocampal and cultured mouse
      cortical neurons against NMDA receptor-mediated excitotoxicity. The present study
      was conducted to determine whether apelin-13 provides protection in transient
      focal cerebral ischemia. Focal ischemia was induced by 60-min middle cerebral
      artery occlusion (MCAO), followed by 23-h reperfusion. Saline as a vehicle and
      apelin-13 at doses of 25, 50, and 100 MUg were injected intracerebroventriculary
      (ICV) at the beginning of ischemia. Infarct volume ,brain edema, motor
      dysfunction, and apoptosis were assessed 24 h after MCAO. Treatment with apelin
      13 at doses of 50 and 100 MUg ICV markedly reduced total infarct volumes by 45
      and 55 %, respectively (P < 0.001), but injection of apelin at lower dose (25
      MUg) did not change infarct volume significantly (P > 0.05). In addition, apelin
      13 at doses of 50 and 100 MUg reduced brain edema (P < 0.001) and inhibited
      apoptosis by decreasing caspase-3 activation (P < 0.001). Apelin-13 did not
      significantly change neurological dysfunction (P > 0.05).

PMID- 22638859
TI  - Detection of autoantibodies and increased concentrations of interleukins in
      plasma from patients with Tourette's syndrome.
AB  - The aim of this study was to assess levels of autoantibodies and cytokines in
      patients with Tourette's syndrome (TS, n = 40) and healthy control individuals (n
      = 40). Plasma interleukin (IL)-1beta, IL-6, IL-17, and soluble gp130
      concentrations were significantly higher in the TS group compared with the
      control group (P < 0.001); whereas the soluble IL-6 receptor concentration was
      significantly decreased in the TS group compared with the control group (P <
      0.001). Significantly more patients in the TS group were positive for antibrain
      and antinuclear antibodies, and antistreptolysin compared with the control group
      (P < 0.05). These findings suggest that immune activity is altered in patients
      with TS.

PMID- 22638860
TI  - Neuroprotection by silencing iNOS expression in a 6-OHDA model of Parkinson's
      disease.
AB  - In this study, we investigated the protective role of silenced iNOS expression in
      neuron death in the nigrostriatal pathway in a 6-OHDA animal model of Parkinson's
      disease (PD). The animal model was established by intrastriatal infusion of a
      single dose of 6-OHDA. Silencing of iNOS expression was established by
      intrastriatal infusion of adenovirus-carried iNOS-targeted small interfering RNA
      (siRNA). Apomorphine-induced rotation behavior was measured. Expression of iNOS,
      OX-42, and TH; levels of DA, DOPAC, and HVA in the striatum; and the levels of
      p53 phosphorylation, Bax, and cleaved caspase-3 (CC3) in the substantia nigra
      were measured. We demonstrated that co-infusion of 6-OHDA with adenovirus
      expressing siRNA of iNOS blocked the activation of microglia, iNOS transcription,
      and p53-Bax-CC3 apoptotic cascade as well as significantly blocking 6-OHDA
      induced decreases in DA, DOPAC, HVA, and TH levels and effectively decreased
      rotation number. Our study highlighted the role of iNOS in the neurodegeneration
      of nigrostriatal dopaminergic neurons in the 6-OHDA animal model of PD and
      suggested that the microglial activation-iNOS-p53-Bax-CC3 apoptotic pathway plays
      a key role in the neurodegeneration in the 6-OHDA model.

PMID- 22638862
TI  - Bacterial species-characteristic profiles of molecular species, and the
      antigenicity of phospholipids and glycolipids in symbiotic Lactobacillus,
      Staphylococcus and Streptococcus species.
AB  - Human symbiotic bacteria, Lactobacillus reuteri (LR) in the intestines,
      Staphylococcus epidermidis (SE) in skin and Streptococcus salivalis (SS) in the
      oral cavity, contain dihexaosyl diglycerides (DH-DG) in concentrations equivalent
      to those of phosphatidyl glycerol (PG) and cardiolipin (CL), together with mono-
      to tetrahexaosyl DGs. The molecular species, as the combination of fatty acids in
      the DG moiety, were revealed to be bacterial species-characteristic, but to be
      similar between glycolipids and phospholipids in individual bacteria, the major
      ones being 16:0 and cy19:0 for LR, ai15:0 and ai17:0 for SE, and 16:0 and 18:1
      for SS, respectively. The carbohydrate structures of DH-DGs were also bacterial
      species-characteristic, being Galalpha1-2Glcalpha for LR, Glcbeta1-6Glcbeta for
      SE, and Glcalpha1-2Glcalpha for SS, respectively. Also, bacterial glycolipids
      were revealed to provide antigenic determinants characteristic of bacterial
      species on immunization of rabbits with the respective bacteria. Anti-L.
      johnsonii antiserum intensely reacted with tri- and tetrahexaosyl DGs, in which
      Galalpha was bound to DH-DG through an alpha1-6 linkage, as well as with DH-DG
      from LR. Although anti-SE antiserum preferentially reacted with DH-DG from SE,
      anti-SS antiserum reacted with DH-DG from SS and, to a lesser extent, with DH-DGs
      from LR and SE. But, both anti-SE and anti-SS antiserum did not react at all with
      monohexaosyl DG or glycosphingolipids with the same carbohydrates at the
      nonreducing terminals. In addition, 75 % of human sera, irrespective of the ABO
      blood group, were found to contain IgM to tri- and tetrahexaosyl DGs from LR, but
      not to DH-DGs from LR, SE and SS.

PMID- 22638861
TI  - "Casting" light on the role of glycosylation during embryonic development:
      insights from zebrafish.
AB  - Zebrafish (Danio rerio) remains a versatile model organism for the investigation
      of early development and organogenesis, and has emerged as a valuable platform
      for drug discovery and toxicity evaluation [1-6]. Harnessing the genetic power
      and experimental accessibility of this system, three decades of research have
      identified key genes and pathways that control the development of multiple organ
      systems and tissues, including the heart, kidney, and craniofacial cartilage, as
      well as the hematopoietic, vascular, and central and peripheral nervous systems
      [7-31]. In addition to their application in large mutagenic screens, zebrafish
      has been used to model a variety of diseases such as diabetes, polycystic kidney
      disease, muscular dystrophy and cancer [32-36]. As this work continues to
      intersect with cellular pathways and processes such as lipid metabolism,
      glycosylation and vesicle trafficking, investigators are often faced with the
      challenge of determining the degree to which these pathways are functionally
      conserved in zebrafish. While they share a high degree of genetic homology with
      mouse and human, the manner in which cellular pathways are regulated in zebrafish
      during early development, and the differences in the organ physiology, warrant
      consideration before functional studies can be effectively interpreted and
      compared with other vertebrate systems. This point is particularly relevant for
      glycosylation since an understanding of the glycan diversity and the mechanisms
      that control glycan biosynthesis during zebrafish embryogenesis (as in many
      organisms) is still developing.Nonetheless, a growing number of studies in
      zebrafish have begun to cast light on the functional roles of specific classes of
      glycans during organ and tissue development. While many of the initial efforts
      involved characterizing identified mutants in a number of glycosylation pathways,
      the use of reverse genetic approaches to directly model glycosylation-related
      disorders is now increasingly popular. In this review, the glycomics of zebrafish
      and the developmental expression of their glycans will be briefly summarized
      along with recent chemical biology approaches to visualize certain classes of
      glycans within developing embryos. Work regarding the role of protein-bound
      glycans and glycosaminoglycans (GAG) in zebrafish development and organogenesis
      will also be highlighted. Lastly, future opportunities and challenges in the
      expanding field of zebrafish glycobiology are discussed.

PMID- 22638863
TI  - Glycoblotting-based high throughput protocol for the structural characterization
      of hyaluronan degradation products during enzymatic fragmentation.
AB  - Increasing interests have been focused on the functional roles of hyaluronan
      degradation products, namely hyaluronan oligosaccharides, as signal molecules
      regulating cell growth, differentiation, malignancy, and inflammatory responses.
      It is clear that molecular size of hyaluronan oligosaccharides might be crucial
      for defining possible and dynamic roles in supporting and suppressing homeostatic
      cellular processes. The present paper communicates a facile and efficient
      approach based on glycoblotting method for the characterization of hyaluronan
      fragments liberated from three different sources of hyaluronan (rooster comb,
      bovine vitreous humor, and Streptococcus) by in vitro degradation using two
      typical hyaluronidases of bovine testicular (EC 3.2.1.35) and Streptomyces
      hyalurolyticus (EC 4.2.2.1). It was demonstrated that glycoblotting method allows
      for high throughput and quantitative analysis of hyaluronan fragments within a
      wide dynamic range (1 ~ 1,000 pmole) when 5 MUg of hyaluronan digests were
      applied for this enrichment protocol. Molecular size and distribution of
      hyaluronan fragments were proved to be influenced strongly by conditions and
      hyaluronidases employed while source of hyaluronan did not affect the degradation
      profiles. Strikingly, the present method uncovered the existence of the smallest
      and unusual hyaluronan degradation fragments such as a disaccharide GlcAbeta1
      3GlcNAc during the digestion by bovine hyaluronidase and a trisaccharide
      GlcAbeta1-3GlcNAcbeta1-4GlcA derivative by Streptomyces hyaluronidase. Bovine
      testis hyaluronidases afforded hyaluronan tetra- and hexasaccharides as major
      products. On the other hand, it was demonstrated that Streptomyces hyaluronidase
      can produce odd number fragments from three to nine sugar residues while even
      number fragments from four to fourteen sugar residues were major products.

PMID- 22638864
TI  - The diagnostic value of a single measurement of superior vena cava flow in the
      first 24 h of life in very preterm infants.
AB  - Low superior vena cava (SVC) flow has been associated with intraventricular
      haemorrhage (IVH) in very preterm infants. We studied the diagnostic value of a
      single measurement of SVC flow within the first 24 h of life in very preterm
      infants and its association with occurrence or extension of IVH in a setting of
      limited availability of neonatal echocardiography. Preterm infants who were born
      at less than 30 weeks gestation and who had an echocardiogram within 24 h after
      birth were eligible. Baseline, clinical and ultrasound data were collected. A
      total of 165 preterm infants were included. Low SVC flow (<41 ml/kg/min) occurred
      in six infants and was associated with severe IVH and extension of IVH, although
      this was not significant after adjusting for confounders. The only independently
      associated variable with low SVC flow was admission temperature (odds ratio 0.27,
      p = 0.001). A review of SVC flow values shows that these are higher now than
      initially reported. This study does not show an association of low SVC flow and
      severe IVH or extension of IVH after adjusting for confounders as a single
      measurement of SVC flow did not add any diagnostic value in this cohort. Thus,
      the exact role of SVC flow measurements in the circulatory assessment of preterm
      infants remains to be elucidated. However, admission temperature may have an
      effect on systemic blood flow in very preterm infants.

PMID- 22638865
TI  - Predictors of screening for AIDS clinical trials among African-Americans and
      Latino/Hispanics enrolled in an efficacious peer-driven intervention: uncovering
      socio-demographic, health, and substance use-related factors that promote or
      impede screening.
AB  - African-American and Latino/Hispanic persons living with HIV/AIDS are
      underrepresented in AIDS clinical trials (ACTs). The aim of this paper was to
      uncover factors, either unmodifiable or not directly targeted for change, that
      predicted screening for ACTs during an efficacious peer-driven intervention (N =
      540 total; N = 351 in an intervention arm, N = 189 control). This paper focused
      on participants assigned to an intervention arm, 56 % of whom were screened for
      ACTs. We found a decreased odds of screening was associated with closer proximity
      to the screening site, gay/lesbian orientation, lower mental health symptoms,
      current injection drug use, more recent HIV diagnosis, lack of prior screening
      experience, and failure to attend all intervention sessions, but there were no
      gender or racial/ethnic differences. Efforts to reduce racial/ethnic disparities
      in ACTs can be enhanced by attending to these specific factors, which may
      interfere with programmatic efforts to increase African-American and
      Latino/Hispanic representation in ACTs.

PMID- 22638866
TI  - The relationship between perceived discrimination and high-risk social ties among
      illicit drug users in New York City, 2006-2009.
AB  - Discrimination can influence risk of disease by promoting unhealthy behaviors
      (e.g., smoking, alcohol use). Whether it influences the formation of high-risk
      social ties that facilitate HIV transmission is unclear. Using cross-sectional
      data from a cohort of illicit drug users, this study examined the association
      between discrimination based on race, drug use and prior incarceration and risky
      sex and drug ties. Negative binomial regression models were performed.
      Participants who reported discrimination based on race and drug use had
      significantly more sex and drug-using ties. But, after accounting for both racial
      and drug use discrimination, only racial discrimination was associated with
      increased sex, drug-using, and injecting ties. Drug users who experience
      discrimination and subsequently develop more sex and drug-using ties, increase
      their risk of contracting HIV. Future longitudinal studies illuminating the
      pathways linking discrimination and social network development may guide
      intervention development and identify drug-using subpopulations at high risk for
      disease transmission.

PMID- 22638867
TI  - Delineating interpersonal communication networks: a study of the diffusion of an
      intervention among female entertainment workers in Shanghai, China.
AB  - Diffusion of innovation (DOI) is widely cited in the HIV behavior change
      literature; however there is a dearth of research on the application of DOI in
      interventions for sex workers. Following a randomized-controlled trial of HIV
      risk reduction among female entertainment workers (FEWs) in Shanghai, China, we
      used qualitative approaches to delineate potential interpersonal communication
      networks and contributing factors that promote diffusion of information in
      entertainment venues. Results showed that top-down communication networks from
      the venue owners to the FEWs were efficient for diffusion of information.
      Mammies/madams, who act as intermediaries between FEWs and clients form an
      essential part of FEWs' social networks but do not function as information
      disseminators due to a conflict of interest between safer sex and maximizing
      profits. Diffusion of information in large venues tended to rely more on aspects
      of the physical environment to create intimacy and on pressure from managers to
      stimulate communication. In small venues, communication and conversations
      occurred more spontaneously among FEWs. Information about safer sex appeared to
      be more easily disseminated when the message and the approach used to convey
      information could be tailored to people working at different levels in the
      venues. Results suggest that safer sex messages should be provided consistently
      following an intervention to further promote intervention diffusion, and health
      related employer liability systems in entertainment venues should be established,
      in which employers are responsible for the health of their employees. Our study
      suggests that existing personal networks can be used to disseminate information
      in entertainment venues and one should be mindful about the context-specific
      interactions between FEWs and others in their social networks to better achieve
      diffusion of interventions.

PMID- 22638868
TI  - Effect of compression on non-isothermal crystallization behaviour of amorphous
      indomethacin.
AB  - PURPOSE: To evaluate the effect of tablet compression on the physical stability
      of amorphous indomethacin. METHODS: The amorphous indomethacin generated by melt
      cooling, rapid (5 degrees C/min) or slow (0.2 degrees C/min) cooling, was
      evaluated by PXRD, mDSC and FTIR analysis. Non-isothermal crystallisation
      behaviour was assessed using mDSC and any structural changes with compression
      were monitored by FTIR. Amorphous indomethacin was compressed in a DSC pan using
      a custom made die cavity-punch setup and further analysed in the primary
      container to minimize stress due to sample transfer and preparation. RESULTS:
      Compression of amorphous indomethacin induced and increased the extent of
      crystallisation upon heating. DSC results revealed that amorphous indomethacin
      generated by rapid cooling is more prone to compression induced crystallisation
      than the slowly cooled one. Onset temperature for crystallisation (T(c)) of
      uncompressed slowly and rapidly cooled samples are 121.4 and 124 degrees C and
      after compression T(c) decreased to ca 109 and ca 113 degrees C, respectively.
      Compression of non-aged samples led to higher extent of crystallisation
      predominantly into gamma-form. Aging followed by compression led to
      crystallisation of mainly the alpha-form. CONCLUSIONS: Compression affects the
      physical stability of amorphous indomethacin. Structural changes originated from
      tablet compression should be duly investigated for the stable amorphous
      formulation development.

PMID- 22638869
TI  - CriticalSorbTM promotes permeation of flux markers across isolated rat intestinal
      mucosae and Caco-2 monolayers.
AB  - PURPOSE: CriticalSorbTM is a novel absorption enhancer based on Solutol((r))
      HS15, one that has been found to enhance the nasal transport. It is in clinical
      trials for nasal delivery of human growth hormone. The hypothesis was that
      permeating enhancement effects of the Solutol((r))HS15 component would translate
      to the intestine. METHODS: Rat colonic mucosae were mounted in Ussing chambers
      and Papp values of [(14)C]-mannitol, [(14)C]-antipyrine, FITC-dextran 4000 (FD
      4), and TEER values were calculated in the presence of CriticalSorbTM. Tissues
      were fixed for H & E staining. Caco-2 monolayers were grown on TranswellsTM for
      similar experiments. RESULTS: CriticalSorbTM(0.01% v/v) significantly increased
      the Papp of [(14)C]-mannitol, FD-4 [(14)C]-antipyrine across ileal and colonic
      mucosae, accompanied by a decrease in TEER. In Caco-2 monolayers, it also
      increased the Papp of [(14)C]-mannitol FD-4 and [(14)C]-antipyrine over 120 min.
      In both monolayers and tissues, it acted as a moderately effective P-glycoprotein
      inhibitor. There was no evidence of cytotoxicity in Caco-2 at concentrations of
      0.01% for up to 24 h and histology of tissues showed intact epithelia at 120 min.
      CONCLUSIONS: Solutol((r)) HS15 is the key component in CriticalSorbTM that
      enables non-cytotoxic in vitro intestinal permeation and its mechanism of action
      is a combination of increased paracellular and transcellular flux.

PMID- 22638870
TI  - Characterization of a nanoparticulate drug delivery system using scanning ion
      occlusion sensing.
AB  - PURPOSE: To explore the application of scanning ion occlusion sensing (SIOS) as a
      novel technology for characterization of nanoparticles. METHODS: Liposomes were
      employed as model nanoparticles. The size distribution of the liposomes was
      measured by both SIOS and dynamic light scattering (DLS). Particle number
      concentration was determined based on particle translocation rate. The ability of
      SIOS and DLS to resolve bimodal samples was evaluated by measuring a mixture of
      217 and 355 nm standard nanoparticles. Opsonization of liposomes by plasma was
      also studied using SIOS. RESULTS: SIOS was shown to measure the size of different
      liposomes with higher sensitivity than DLS and it requires a smaller sample
      volume than DLS. With appropriate calibration, SIOS could be used to determine
      particle number concentrations. In comparison, SIOS analysis of the mixture
      showed accurate resolution of the population as a bimodal distribution over a
      wide range of number ratios of the particles. SIOS could detect plasma
      opsonization of liposomes by demonstrating a increase in particle size and also
      changes in the particle translocation rate. CONCLUSION: SIOS is a useful
      technology for nanoparticle characterization. It shows some advantages over DLS
      and is clearly a useful tool for the study of nanoparticle drug delivery systems.

PMID- 22638871
TI  - Toxicity studies of poly(anhydride) nanoparticles as carriers for oral drug
      delivery.
AB  - PURPOSE: To evaluate the acute and subacute toxicity of poly(anhydride)
      nanoparticles as carriers for oral drug/antigen delivery. METHODS: Three types of
      poly(anhydride) nanoparticles were assayed: conventional (NP), nanoparticles
      containing 2-hydroxypropyl-beta-cyclodextrin (NP-HPCD) and nanoparticles coated
      with poly(ethylene glycol) 6000 (PEG-NP). Nanoparticles were prepared by a
      desolvation method and characterized in terms of size, zeta potential and
      morphology. For in vivo oral studies, acute and sub-acute toxicity studies were
      performed in rats in accordance to the OECD 425 and 407 guidelines respectively.
      Finally, biodistribution studies were carried out after radiolabelling
      nanoparticles with (99m)technetium. RESULTS: Nanoparticle formulations displayed
      a homogeneous size of about 180 nm and a negative zeta potential. The LD(50) for
      all the nanoparticles tested was established to be higher than 2000 mg/kg bw. In
      the sub-chronic oral toxicity studies at two different doses (30 and 300 mg/kg
      bw), no evident signs of toxicity were found. Lastly, biodistribution studies
      demonstrated that these carriers remained in the gut with no evidences of
      particle translocation or distribution to other organs. CONCLUSIONS:
      Poly(anhydride) nanoparticles (either conventional or modified with HPCD or
      PEG6000) showed no toxic effects, indicating that these carriers might be a safe
      strategy for oral delivery of therapeutics.

PMID- 22638873
TI  - Mini-invasive robot-assisted surgery of the brachial plexus: a case of
      intraneural perineurioma.
AB  - Brachial plexus surgery requires extensive incisions. They are esthetically
      unsightly and compromise the quality of recovery after nerve repair surgery. We
      present a new approach to brachial plexus surgery using mini-invasive robot
      assisted surgery to perform a biopsy of an intraneural perineurioma of the right
      brachial plexus in a 12-year-old girl.

PMID- 22638872
TI  - Physiologically based modeling of pravastatin transporter-mediated hepatobiliary
      disposition and drug-drug interactions.
AB  - PURPOSE: To develop physiologically based pharmacokinetic (PBPK) model to predict
      the pharmacokinetics and drug-drug interactions (DDI) of pravastatin, using the
      in vitro transport parameters. METHODS: In vitro hepatic sinusoidal active
      uptake, passive diffusion and canalicular efflux intrinsic clearance values were
      determined using sandwich-culture human hepatocytes (SCHH) model. PBPK modeling
      and simulations were implemented in Simcyp (Sheffield, UK). DDI with OATP1B1
      inhibitors, cyclosporine, gemfibrozil and rifampin, was also simulated using
      inhibition constant (Ki) values. RESULTS: SCHH studies suggested active uptake,
      passive diffusion and efflux intrinsic clearance values of 1.9, 0.5 and 1.2
      MUL/min/10(6)cells, respectively, for pravastatin. PBPK model developed, using
      transport kinetics and scaling factors, adequately described pravastatin oral
      plasma concentration-time profiles at different doses (within 20% error). Model
      based prediction of DDIs with gemfibrozil and rifampin was similar to that
      observed. However, pravastatin-cyclosporine DDI was underpredicted (AUC ratio 4.4
      Vs ~10). Static (R-value) model predicted higher magnitude of DDI compared to the
      AUC ratio predicted by the PBPK modeling. CONCLUSIONS: PBPK model of pravastatin,
      based on in vitro transport parameters and scaling factors, was developed. The
      approach described can be used to predict the pharmacokinetics and DDIs
      associated with hepatic uptake transporters.

PMID- 22638874
TI  - Robot-assisted free toe pulp transfer: feasibility study.
AB  - The current tendency of microsurgery is heading toward supermicrosurgery and
      microsurgery assisted by robotics. The aim of this work was to study the
      feasibility of a free hallux hemipulp transfer with a surgical robot in a
      cadaveric model. We used a human body. The intervention was realized by a Da
      Vinci SI(r) robot (Intuitive SurgicalTM, Sunnyvale, CA) in two stages: first
      taking off the medial hallux hemipulp, then transferring the hallux hemipulp to
      the radial thumb hemipulp. The intervention lasted 1 hour 59 minutes, exclusively
      with the Da Vinci SI(r) robot, without any interruption or outside intervention.
      Despite the absence of sensory feedback and an intervention 25% longer than in
      conventional microsurgery, we have demonstrated the feasibility of free hallux
      hemipulp transfer with a surgical robot. In the future, it is likely that the
      added benefits of the robot (physiological tremor suppression, user-friendly
      ergonomics, ultraprecise control of the instruments) will make the robot an
      indispensable tool for the surgeon.

PMID- 22638875
TI  - Robot-assisted oropharyngeal reconstruction with free tissue transfer.
AB  - The surgical robot has been demonstrated to have useful applications in urologic,
      gynecologic, cardiac, general, and endocrine surgery. The development of robotic
      surgery has enhanced the precision and control of the surgeon in minimally
      invasive surgical situations specific to these specialties and, more recently,
      has been applied to the treatment of oropharyngeal tumors in the form of
      transoral robotic surgery (TORS). The elimination of the need for lip- and
      mandible-splitting approaches has allowed a reassessment of surgical options for
      the treatment of tumors that have until recently been primarily addressed
      nonoperatively with chemoradiation. The TORS approach has created the need to
      adapt current reconstructive options to robotic technology to manage the
      resultant tissue defects and to assess and compare the effectiveness of these
      procedures. This report details our early experience with the use of robot
      assisted free tissue transfer for management of soft tissue defects of the
      oropharynx.

PMID- 22638876
TI  - Nonaneurysmal subarachnoid hemorrhage: an update.
AB  - Nonaneurysmal subarachnoid hemorrhage (NA-SAH) constitutes a heterogeneous group
      of patients, both perimesencephalic (PMN-SAH) and non-perimesencephalic (nPMN
      SAH). Despite many reports and case series, the etiology of NA-SAH remains
      uncertain. The differences in clinical course and outcome between PMN-SAH and
      nPMN-SAH are evident and have to be taken into consideration at the time of
      admission, as aggressive diagnostic evaluation and management are required for
      latter patient. In terms of diagnostic evaluation, the most important
      determination is to differentiate PMN-SAH from nPMN-SAH and aneurysmal SAH. PMN
      SAH can be distinguished on CT in the majority of patients, but should be
      confirmed by a negative cerebral angiography. In addition, Convexal NA-SAH is
      another important subtype of NA-SAH associated with diverse etiologies and
      symptoms, although prognosis is generally favorable.

PMID- 22638877
TI  - Anticoagulation-related intracranial hemorrhages.
AB  - Unfractionated heparin, low molecular weight heparin, and warfarin are often used
      for patients at high risk of thromboembolism and are associated with increased
      risk of major and even life threatening hemorrhages. They are in use for a long
      time and have treatment strategies in place in an event of life threatening
      intracranial hemorrhage. The advent of newer anticoagulants, direct thrombin
      inhibitors (dabigatran) and two factor Xa inhibitors (rivaroxaban and apixaban),
      has increased the options of anticoagulation for patients with atrial
      fibrillation and venous thrombosis, but at the same time, in the absence of an
      antidote, they have created a great challenge for treating physicians to manage
      intracranial bleeding related to these agents. In this paper, we will briefly
      summarize the state of knowledge regarding the risk of anticoagulation-related
      ICH, and review basic concepts on anticoagulation reversal and the general
      management of patients with this complication.

PMID- 22638881
TI  - Evaluation of plasmid and genomic DNA calibrants used for the quantification of
      genetically modified organisms.
AB  - The reliable quantification of genetically modified organisms (GMOs) by real-time
      PCR requires, besides thoroughly validated quantitative detection methods,
      sustainable calibration systems. The latter establishes the anchor points for the
      measured value and the measurement unit, respectively. In this paper, the
      suitability of two types of DNA calibrants, i.e. plasmid DNA and genomic DNA
      extracted from plant leaves, for the certification of the GMO content in
      reference materials as copy number ratio between two targeted DNA sequences was
      investigated. The PCR efficiencies and coefficients of determination of the
      calibration curves as well as the measured copy number ratios for three powder
      certified reference materials (CRMs), namely ERM-BF415e (NK603 maize), ERM-BF425c
      (356043 soya), and ERM-BF427c (98140 maize), originally certified for their mass
      fraction of GMO, were compared for both types of calibrants. In all three systems
      investigated, the PCR efficiencies of plasmid DNA were slightly closer to the PCR
      efficiencies observed for the genomic DNA extracted from seed powders rather than
      those of the genomic DNA extracted from leaves. Although the mean DNA copy number
      ratios for each CRM overlapped within their uncertainties, the DNA copy number
      ratios were significantly different using the two types of calibrants. Based on
      these observations, both plasmid and leaf genomic DNA calibrants would be
      technically suitable as anchor points for the calibration of the real-time PCR
      methods applied in this study. However, the most suitable approach to establish a
      sustainable traceability chain is to fix a reference system based on plasmid DNA.

PMID- 22638878
TI  - The mean and noise of protein numbers in stochastic gene expression.
AB  - Gene expression is the central process in cells, and is stochastic in nature. In
      this work, we study the mean expression level of, and the expression noise in, a
      population of isogenic cells, assuming that transcription is activated by two
      sequential exponential processes of rates kappa and lambda. We find that the mean
      expression level often displays oscillatory dynamics, whereas most other models
      suggest that it always grows monotonically. We show that, given the same average
      gene off duration, the asymptotic expression noise increases with |kappa -
      lambda|, and is thus maximized when either kappa -> infinity or lambda ->
      infinity, for which the two exponential processes approach to one process. It
      suggests that natural selection may favor two or more rate-limiting steps for
      gene transcription activation. Our analysis reveals that, at steady-state, the
      noise equals the inverse of the mean, plus the normalized covariance of the mRNA
      and protein copy numbers. This interesting identity partially explains a recent
      striking finding that the protein noises of many Escherichia coli genes were
      close to the inverse of the mean protein levels, and simultaneously, the protein
      and mRNA copy numbers within the individual cells were uncorrelated. We show
      further that the protein noise is close to the inverse of the mean if the gene is
      transcribed effectively and almost continuously, and the protein molecules are
      considerably more stable than the mRNAs. Such phenomenon has been observed
      repeatedly in the synthetic reporter genes controlled by strong promoters and
      tagged with fluorescent labels. 

PMID- 22638882
TI  - Pesticides in seaweed: optimization of pressurized liquid extraction and in-cell
      clean-up and analysis by liquid chromatography-mass spectrometry.
AB  - Chemical residues, such as insecticides and anthelmintics, are frequently
      redistributed from the aquatic environment to marine species. This work reports
      on a fast validated protocol for the analysis of azamethiphos, three avermectins,
      two carbamates and two benzoylurea pesticides and chemotherapeutic agents in
      seaweeds based on pressurized liquid extraction and separation of analytes by
      liquid chromatography coupled with tandem mass spectrometry. The variables
      affecting the efficiency of pressurized liquid extraction, including temperature,
      number of extraction cycles, static extraction time and percent acetonitrile
      flush volume, were studied using a Doehlert design. The optimum parameters were
      100  degrees C and one cycle of 3 min with 70 % acetonitrile. Adequate in-cell
      clean-up of the seaweeds was achieved using 0.8 g of Florisil over 0.1 g of
      graphitized carbon black on the bottom of the cell. The optimized method was
      validated using an analyte-free seaweed sample fortified at different
      concentrations. The limits of quantification ranged from 3.6 MUg kg(-1)
      (azamethiphos) to 31.5 MUg kg(-1) (abamectin). The recovery was from 87 to 120 %
      in most cases at different spiking levels. Finally, the reproducibility of the
      method expressed as the relative standard deviation and evaluated at
      concentrations of 10 and 50 MUg kg(-1) was in the range 9-14.3 % and 6.1-12.3 %,
      respectively. The applicability of the method was evaluated with five commercial
      and 12 wild edible seaweeds, and four target compounds were detected in two wild
      seaweeds at a concentration below the quantification limit.

PMID- 22638883
TI  - The identification of significant chromosomal regions correlated with oral tongue
      cancer progression.
AB  - PURPOSE: Oral squamous cell carcinoma (OSCC) is associated with substantial
      mortality and morbidity, and oral tongue squamous cell carcinoma (SCC) is
      representative in OSCC. Early detection of oral premalignant lesions (OPLs) that
      will develop into invasive tumors is necessary to improve the poor prognosis of
      this cancer. METHODS: To identify potential biomarkers that could be used for
      early detection, we compared the gene expression of incident primary oral tongue
      SCC, severe dysplasia, mild and moderate dysplasia. For this, we used three
      expression datasets obtained from a public database and selected chromosomal
      locations related with the progress of oral tongue cancer from a dataset. We then
      evaluated the gene set, which is included in the selected chromosomal locations,
      using out of bag (OOB) error and plots in two validation datasets. RESULTS: Sixty
      two chromosomal locations were detected, and most genomic aberrations were shown
      in chromosome 3. We identified 62 genes included in those locations, and three
      precancerous and SCC groups were well classified with low OOB error rates. These
      were also discriminative in the two validation datasets. CONCLUSIONS: The
      selected probes with genomic alteration in low-grade dysplasia can be used as an
      effective predictor for disease progression.

PMID- 22638884
TI  - The expression and clinical significance of circulating microRNA-21 in serum of
      five solid tumors.
AB  - PURPOSE: MicroRNA-21 (miR-21) was reported as being overexpressed in various
      human cancerous tissues, but its expression in cancerous serum was not unanimous
      in different laboratories. On the base of optimizing experimental design and
      improving trial protocol, we wanted to know whether the circulating microRNA-21
      was dysregulated in the common solid cancers. METHODS: Using SYBR green real-time
      quantitative reverse transcription-PCR, we detected the expression of circulating
      miR-21 in 174 patients with solid cancers and 39 normal control subjects,
      including breast cancer, esophageal cancer, gastric cancer, colorectal cancer,
      lung cancer. Furthermore, we analyzed the associations between miR-21 expression
      and clinical features of patients. RESULTS: miR-21 was significantly
      overexpressed in human solid cancerous serum relative to normal control (P <
      0.001), and its sensitivity and specificity were significantly higher than the
      currently used tumor markers. High miR-21 expression was not correlated with
      gender, age, clinical stage, and lymph node metastasis status. CONCLUSION:
      Circulating miR-21 could serve as a potential broad-spectrum serum-based
      biomarker for the detection of some solid cancers.

PMID- 22638885
TI  - Intralymphatic delivery of platinum-based chemotherapeutics is possible: an
      experimental study.
AB  - PURPOSE: Systemic chemotherapy regimens with cisplatinum have been associated
      with several toxicities. Thus, a loco-regional therapy approach may greatly
      reduce the toxicity. For this purpose, we designed this experimental study to
      investigate whether local chemotherapeutic injection is superior to systemic
      cisplatinum injection for retroperitoneal lymph nodes. METHODS: A total of 48
      male Wistar rats were included to the study. Rats were divided into six groups.
      In the first three groups, systemic applications of cisplatinum, carboplatinum
      and oxaliplatin were performed, respectively. In the last three, local
      administration of cisplatinum, carboplatinum and oxaliplatin was performed,
      respectively. One hour after the chemotherapeutic agent applications,
      retroperitoneal lymph nodes were dissected and platinum concentrations were
      analyzed. RESULTS: When compared with systemic route, achieving higher platinum
      concentrations in the local chemotherapeutic application groups was the most
      spectacular result of the study. Serum platinum concentrations were also lower in
      the local application groups than systemic ones. When we compared local and
      systemic applications between three chemotherapeutic agents, the most significant
      concentration difference was seen in carboplatinum group. CONCLUSION: The results
      of this study demonstrate that intralymphatic delivery of cisplatinum,
      carboplatinum and oxaliplatin leads to higher drug concentrations in the
      retroperitoneal lymph nodes when compared with intravenous administration.

PMID- 22638889
TI  - Diagnostic value of biochemical biomarkers in malignant and non-malignant
      pericardial effusion.
AB  - The aim of this study was to examine the biochemical composition of pericardial
      effusions of different etiology and to evaluate the diagnostic utility of
      biochemical parameters and tumor markers to discriminate malignant from benign
      effusion. Pericardial and serum levels of biochemical parameters and tumor
      markers were compared in 105 patients who underwent pericardiocentesis and
      pericardioscopy with targeted epicardial biopsy. Etiologic diagnosis was based on
      pericardial fluid and epicardial biopsy analysis by cytology, histology,
      immunohistochemistry, microbiology and polymerase chain reaction. The total of
      105 patients comprised 29 patients with malignant and 76 patients with non
      malignant pericardial effusions (40 autoreactive, 28 viral, 5 postcardiotomy
      syndromes and 3 associated with systemic diseases). Malignant pericardial
      effusions had significantly higher pericardial fluid levels of the tumor markers
      CEA, CA 19-9, CA 72-4, SCC and NSE (p < 0.001, p = 0.002, p < 0.001, p = 0.004
      and p < 0.001, respectively) as well as higher pericardial fluid hemoglobin (p <
      0.001), pericardial fluid white blood cells (p = 0.003), pericardial fluid LDH (p
      < 0.001) and ratio of pericardial to serum LDH levels compared to benign
      effusions. None of the biochemical or cell-count parameters tested proved to be
      accurate enough for distinguishing malignant from benign effusions. However,
      measurement of pericardial CA 72-4 levels offered a high diagnostic accuracy for
      malignancy, particularly in bloody pericardial effusions. None of the biochemical
      parameters tested was useful for the discrimination of malignant from benign
      effusions. However, measurement of pericardial CA 72-4 levels in bloody
      pericardial effusions yielded a high diagnostic accuracy and thus offers the
      potential as a diagnostic tool to distinguish between malignant and benign
      effusions.

PMID- 22638901
TI  - Evaluating New York City's smoke-free parks and beaches law: a critical
      multiplist approach to assessing behavioral impact.
AB  - This article describes the evaluation of the law banning smoking in New York
      City's parks and beaches that went into effect in 2011. We discuss the practical
      and methodological challenges that emerged in evaluating this law, and describe
      how we applied the principles of critical multiplism to address these issues. The
      evaluation uses data from three complementary studies, each with a unique set of
      strengths and weaknesses that can provide converging evidence for the
      effectiveness of the law. Results from a litter audit and an observational study
      suggest the ban reduced smoking in parks and beaches. The purpose, methodology
      and baseline results from an ongoing survey that measures how frequently adults
      in NYC and across New York State notice people smoking in parks and on beaches
      are presented and discussed. Limitations are considered and suggestions are
      offered for future evaluations of similar policies.

PMID- 22638902
TI  - Effect of the healthy MOMs lifestyle intervention on reducing depressive symptoms
      among pregnant Latinas.
AB  - Depression during the prenatal and postpartum periods is associated with poor
      maternal, perinatal and child outcomes. This study examines the effectiveness of
      a culturally and linguistically tailored, social support-based, healthy lifestyle
      intervention led by trained community health workers in reducing depressive
      symptoms among pregnant and early postpartum Latinas. A sample of 275 pregnant
      Latinas was randomized to the Healthy MOMs Healthy Lifestyle Intervention (MOMs)
      or the Healthy Pregnancy Education (control) group. More than one-third of
      participants were at risk for depression at baseline. MOMs participants were less
      likely than control group participants to be at risk for depression at follow-up.
      Between baseline and 6 weeks postpartum, MOMs participants experienced a
      significant decline in depressive symptoms; control participants experienced a
      marginally significant decline. For MOMs participants, most of this decline
      occurred during the pregnancy intervention period, a time when no change occurred
      for control participants. The change in depressive symptoms during this period
      was greater among MOMs than control participants ("intervention effect"). From
      baseline to postpartum, there was a significant intervention effect among non
      English-speaking women only. These findings provide evidence that a community
      planned, culturally tailored healthy lifestyle intervention led by community
      health workers can reduce depressive symptoms among pregnant, Spanish-speaking
      Latinas.

PMID- 22638903
TI  - A single gene encodes isopentenyl diphosphate isomerase isoforms targeted to
      plastids, mitochondria and peroxisomes in Catharanthus roseus.
AB  - Isopentenyl diphosphate isomerases (IDI) catalyze the interconversion of the two
      isoprenoid universal C5 units, isopentenyl diphosphate and dimethylally
      diphosphate, to allow the biosynthesis of the large variety of isoprenoids
      including both primary and specialized metabolites. This isomerisation is usually
      performed by two distinct IDI isoforms located either in plastids/peroxisomes or
      mitochondria/peroxisomes as recently established in Arabidopsis thaliana mainly
      accumulating primary isoprenoids. By contrast, almost nothing is known in plants
      accumulating specialized isoprenoids. Here we report the cloning and functional
      validation of an IDI encoding cDNA (CrIDI1) from Catharanthus roseus that
      produces high amount of monoterpenoid indole alkaloids. The corresponding gene is
      expressed in all organs including roots, flowers and young leaves where
      transcripts have been detected in internal phloem parenchyma and epidermis. The
      CrIDI1 gene also produces long and short transcripts giving rise to corresponding
      proteins with and without a N-terminal transit peptide (TP), respectively.
      Expression of green fluorescent protein fusions revealed that the long isoform is
      targeted to both plastids and mitochondria with an apparent similar efficiency.
      Deletion/fusion experiments established that the first 18-residues of the N
      terminal TP are solely responsible of the mitochondria targeting while the entire
      77-residue long TP is needed for an additional plastid localization. The short
      isoform is targeted to peroxisomes in agreement with the presence of peroxisome
      targeting sequence at its C-terminal end. This complex
      plastid/mitochondria/peroxisomes triple targeting occurring in C. roseus
      producing specialized isoprenoid secondary metabolites is somehow different from
      the situation observed in A. thaliana mainly producing housekeeping isoprenoid
      metabolites.

PMID- 22638904
TI  - The mRNA of a Knotted1-like transcription factor of potato is phloem mobile.
AB  - Potato Homeobox1 (POTH1) is a Knotted1-like transcription factor from the Three
      Amino Acid Loop Extension (TALE) superfamily that is involved in numerous aspects
      of development in potato (Solanum tuberosum L). POTH1 interacts with its protein
      partner, StBEL5, to facilitate binding to specific target genes to modulate
      hormone levels, mediate leaf architecture, and enhance tuber formation. In this
      study, promoter analyses show that the upstream sequence of POTH1 drives beta
      glucuronidase activity in response to light and in association with phloem cells
      in both petioles and stems. Because POTH1 transcripts have previously been
      detected in phloem cells, long-distance movement of its mRNA was tested. Using RT
      PCR and transgenic potato lines over-expressing POTH1, in vitro micrografts
      demonstrated unilateral movement of POTH1 RNA in a rootward direction. Movement
      across a graft union into leaves from newly arising axillary shoots and roots of
      wild type stocks was verified using soil-grown tobacco heterografts. Leaves from
      the wild type stock containing the mobile POTH1 RNA exhibited a reduction in leaf
      size relative to leaves from wild type grafts. Both untranslated regions of POTH1
      when fused to an expression marker beta-glucuronidase, repressed its translation
      in tobacco protoplasts. RNA/protein binding assays demonstrated that the UTRs of
      POTH1 bind to two RNA-binding proteins, a polypyrimidine tract-binding protein
      and an alba-domain type. Conserved glycerol-responsive elements (GRE), specific
      to alba-domain interaction, are duplicated in both the 5' and 3' untranslated
      regions of POTH1. These results suggest that POTH1 functions as a mobile signal
      in regulating development.

PMID- 22638906
TI  - [Diseases of the neck].

PMID- 22638905
TI  - 8-isoprostane, prostaglandin E2, C-reactive protein and serum amyloid A as
      markers of inflammation and oxidative stress in antiphospholipid syndrome: a
      pilot study.
AB  - OBJECTIVE: To test the inflammation and oxidative stress hypothesis in
      antiphospholipid syndrome (APS) patients and to identify possible associations
      with clinical and laboratory features of the disease. METHODS: Serum amyloid A
      (SAA), C-reactive protein (CRP), 8-isoprostane and prostaglandin E2 (PGE) were
      assayed in the sera of 45 APS patients and then compared to control groups made
      up of 15 antiphospholipid antibody (aPL) negative patients with systemic lupus
      erythematosus, 15 aPL negative subjects with pregnancy-related morbidity, 15 aPL
      negative patients with thrombosis, 15 subjects with persistently positive aPL
      with no signs or symptoms of APS, and 15 healthy volunteers from among the
      hospital staff. RESULTS: APS patients showed significantly higher CRP (p = 0.01),
      SAA (p < 0.01), 8-isoprostane (p = 0.05) and PGE2 (p = 0.001) plasma levels as
      compared to controls. Among APS subjects, significantly higher 8-isoprostane and
      PGE2 levels were observed in patients with triple positivity for aPL (lupus
      anticoagulant, anticardiolipin and anti-beta2-glycoprotein I antibodies) compared
      to APS patients with single or double aPL positivity. CONCLUSION: Both
      inflammation and oxidative stress, as measured by SAA, CRP, 8-isoprostane and
      PGE2, occur in APS and seem to be related to triple positivity for aPL.

PMID- 22638907
TI  - Revascularization for left main and multivessel coronary artery disease in the
      drug-eluting stent era: integration of recent drug-eluting stent trials.
AB  - As older patients comprise a greater proportion of the population, the incidence
      of multivessel and left main coronary artery disease is increasing. Given the
      improvements in percutaneous coronary intervention, more patients are suitable
      for this revascularization strategy. However, the optimal revascularization
      strategy remains a moving target. Numerous trials, extending from the bypass
      surgery versus medical therapy era to the most current drug-eluting stent versus
      bypass surgery era, provide information to select the most appropriate
      revascularization strategy. The objective of this review is to summarize these
      data.

PMID- 22638908
TI  - Is there attenuation of benefit of invasive therapy in patients with chronic
      kidney disease? Results from randomized trials and registry data.
AB  - Chronic kidney disease (CKD) is not only a common comorbidity among patients
      presenting with acute coronary syndrome (ACS), it is also an entity that portends
      worse short- and long-term prognosis. Differences in the pathophysiology of
      arterial atherosclerosis and calcification, chronic inflammation, platelet
      reactivity, and thrombogenicity in patients with and without CKD underpin the
      increased vulnerability of CKD patients with ACS to subsequent ischemic and
      bleeding complications. These differences, as well as the frequent exclusion of
      CKD patients from randomized control trials, create uncertainty regarding the
      benefit of invasive treatment for ACS in patients with CKD. The limited evidence
      from randomized trials suggests a benefit with invasive treatment in CKD patients
      with ACS. However, some data from registry studies suggest no benefit or even
      harm with invasive therapy. Thus, the optimal management of ACS in patients with
      CKD, in particular end-stage CKD, remains uncertain. In this article we review
      the characteristics of coronary artery disease in patients with CKD, the
      available evidence pertaining to the outcomes of CKD patients with ACS with
      invasive versus conservative therapy, and potential areas for reducing
      complications of invasive therapy in this high-risk subset of patients.

PMID- 22638909
TI  - Survivin prevents apoptosis by binding to caspase-3 in astrocytes infected with
      the BeAn strain of Theiler's murine encephalomyelitis virus.
AB  - This paper reports the upregulation of the gene coding for the apoptosis
      regulator family member "surviving" in SJL/J mouse brain astrocyte cultures
      infected with the BeAn strain of TMEV. cRNA from mock- and TMEV-infected SJL/J
      astrocytes was hybridised to an Affymetrix whole murine genome DNA microarray.
      Analysis revealed the upregulation of two sequences coding for the survivin
      protein in infected cells; this was confirmed by RT-PCR and qPCR. Western
      blotting showed an increase in the synthesis of survivin and caspase-3 after
      infection. Unexpectedly, no enzymatic activity was detected in BeAn-infected cell
      lysates in caspase-3-specific colorimetric assays. Cross-linking experiments
      showed survivin and caspase-3 to exist as a complex containing one molecule of
      caspase-3 (17 kDa) and one of either 16 kDa or 14 kDa survivin. The
      neutralization of caspase-3 by survivin-containing lysates was demonstrated using
      recombinant caspase-3. Brains from TMEV-infected mice, but not from naive mice,
      contained survivin mRNA during the acute phase of encephalitis. The present
      results suggest that astrocytes infected by the BeAn strain do not undergo
      apoptosis due to the production of survivin.

PMID- 22638910
TI  - Sleep quality as a potential mediator between psychological distress and diabetes
      quality of life in veterans with type 2 diabetes.
AB  - OBJECTIVE: The goal of this study was to explore sleep quality as a potential
      mediator between depression symptoms and diabetes quality of life (DQOL), and
      anxiety symptoms and DQOL. METHOD: Participants were 83 male and 3 female
      veterans with type 2 diabetes (Mage = 62.4). Self-report measures were completed
      during the baseline assessment of a larger intervention study conducted at the VA
      Boston Healthcare System. RESULTS: Depression symptoms, anxiety symptoms, and
      sleep quality were all associated with DQOL. Additionally, sleep quality had a
      partial indirect effect on the relationships between depression symptoms and
      DQOL, and between anxiety symptoms and DQOL. CONCLUSIONS: These findings suggest
      that sleep quality may have an important role in the way that psychological
      distress affects diabetes quality of life.

PMID- 22638913
TI  - Ovarian cancer stem cells: elusive targets for chemotherapy.
AB  - Ovarian cancer is one of the major causes of death in women with gynecologic
      malignancy. Most patients respond favorably to platinum therapy, but relapses are
      common. There is emerging evidence that a special subset of cells that is highly
      tumorigenic is responsible for recurrence of the disease. This subset of cells
      has been characterized by several groups and has been found to have the
      properties of cancer stem cells. They have been isolated from tumor samples
      obtained during surgical cytoreduction and also from the ascitic fluid of ovarian
      cancer patients. Currently, there are no known unique markers to define these
      cells, but several groups have used different approaches to purify them. Although
      some heterogeneity has been observed in these cells, most of them satisfy the
      functional definition of a stem cell. Advances in characterization of ovarian
      cancer stem cells are instrumental in developing therapies that specifically
      target them. This review describes the advances made in characterization of these
      cells, basis of their resistance to conventional chemotherapeutic agents and the
      prognostic implications of utilizing mechanisms specific to ovarian cancer stem
      cell for therapeutic interventions. Eliminating ovarian cancer stem cells could
      possibly lead to a prolongation of the disease-free survival period and hopefully
      a definitive cure.

PMID- 22638914
TI  - Quantifying and monitoring functional photosystem II and the stoichiometry of the
      two photosystems in leaf segments: approaches and approximations.
AB  - Given its unique function in light-induced water oxidation and its susceptibility
      to photoinactivation during photosynthesis, photosystem II (PS II) is often the
      focus of studies of photosynthetic structure and function, particularly in
      environmental stress conditions. Here we review four approaches for quantifying
      or monitoring PS II functionality or the stoichiometry of the two photosystems in
      leaf segments, scrutinizing the approximations in each approach. (1) Chlorophyll
      fluorescence parameters are convenient to derive, but the information-rich signal
      suffers from the localized nature of its detection in leaf tissue. (2) The gross
      O(2) yield per single-turnover flash in CO(2)-enriched air is a more direct
      measurement of the functional content, assuming that each functional PS II
      evolves one O(2) molecule after four flashes. However, the gross O(2) yield per
      single-turnover flash (multiplied by four) could over-estimate the content of
      functional PS II if mitochondrial respiration is lower in flash illumination than
      in darkness. (3) The cumulative delivery of electrons from PS II to P700(+)
      (oxidized primary donor in PS I) after a flash is added to steady background far
      red light is a whole-tissue measurement, such that a single linear correlation
      with functional PS II applies to leaves of all plant species investigated so far.
      However, the magnitude obtained in a simple analysis (with the signal normalized
      to the maximum photo-oxidizable P700 signal), which should equal the ratio of PS
      II to PS I centers, was too small to match the independently-obtained photosystem
      stoichiometry. Further, an under-estimation of functional PS II content could
      occur if some electrons were intercepted before reaching PS I. (4) The
      electrochromic signal from leaf segments appears to reliably quantify the
      photosystem stoichiometry, either by progressively photoinactivating PS II or
      suppressing PS I via photo-oxidation of a known fraction of the P700 with steady
      far-red light. Together, these approaches have the potential for quantitatively
      probing PS II in vivo in leaf segments, with prospects for application of the
      latter two approaches in the field.

PMID- 22638915
TI  - David Alan Walker (1928-2012).
AB  - David Alan Walker, Emeritus Professor of Biology, University of Sheffield, UK and
      Fellow of the Royal Society, died on February 13, 2012. David had a marvelous 60
      year career as a scientist, during which he was a researcher, mentor, valued
      colleague, and a prolific writer in the field of photosynthesis. His career was
      marked by creative breakthroughs in isolation and analysis of chloroplast
      metabolism in vitro and simple but valuable technical advances for measurement of
      photosynthesis in vivo that remain relevant on a global scale to production of
      crops and biofuels, as well as plant responses to climate change. We include here
      personal remembrances by the authors (GEE and UH), and by (in alphabetical
      order): Zoran Cerovic (France), Bob Furbank (Australia), Geoffrey Hind (USA),
      John Humby (UK), Agu Laisk (Estonia), Peter Lea (UK), Ross Lilley (Australia),
      Barry Osmond (Australia), Simon Robinson (Australia) and Charles Stirling (UK).

PMID- 22638916
TI  - Cervical high-intensity intramedullary lesions in achondroplasia: aetiology,
      prevalence and clinical relevance.
AB  - OBJECTIVES: In achondroplastic patients with slight complaints of medullary
      compression the cervical spinal cord regularly exhibits an intramedullary (CHII)
      lesion just below the craniocervical junction with no signs of focal compression
      on the cord. Currently, the prevalence of the lesion in the general
      achondroplastic population is studied and its origin is explored. METHODS:
      Eighteen achondroplastic volunteers with merely no clinical signs of medullary
      compression were subjected to dynamic magnetic resonance imaging (MRI). The
      presence of a CHII lesion and craniocervical medullary compression in flexed and
      retroflexed craniocervical positions was explored. Several morphological
      characteristics of the craniocervical junction, possibly related to compression
      on the cord, were assessed. RESULTS: A CHII lesion was observed in 39% of the
      subjects and in only one of these was compression at the craniocervical junction
      present. Consequently, no correlation between the CHII lesion and compression
      could be established. None of the morphological characteristics demonstrated a
      correlation with the CHII lesion, except thinning of the cord at the site of the
      CHII lesion. CONCLUSIONS: CHII lesions are a frequent finding in achondroplasia,
      and are generally unaccompanied by clinical symptoms or compression on the cord.
      Further research focusing on the origin of CHII lesions and their clinical
      implications is warranted. KEY POINTS : * MRI now reveals exquisite detail of the
      cervical spinal cord. * Cervical cord lesions are observed in one third of the
      achondroplastic population. * These lesions yield high signal intensity on T2
      weighted MRI. * They are generally unaccompanied by clinical symptoms or cord
      compression. * Their aetiology is unclear and seems to be unrelated to mechanical
      causes.

PMID- 22638917
TI  - Molecular, biochemical, and morphometric characterization of Fasciola species
      potentially causing zoonotic disease in Egypt.
AB  - Fascioliasis is an important disease caused by Fasciola hepatica and Fasciola
      gigantica. The distributions of both species overlap in many areas of Asia and
      Africa including Egypt. Fifty adult Fasciola worms were collected from livers of
      cattle and sheep slaughtered in abattoirs, Cairo, Egypt. They were subjected to
      morphological and metric assessment of external features of fresh adults,
      morphological and metric assessment of internal anatomy of stained mounted worms,
      determination of electrophorezed bands of crude adult homogenates using SDS-PAGE,
      and molecular characterization of species-specific DNA segments using RFLP-PCR.
      It was found that the correlation between conventional morphology and its
      morphotype was statistically significant (P value = 0.00). Using SDS-PAGE, 13
      bands were detected among both genotypes of Fasciola (35.7, 33.6, 32.4, 29.3,
      27.5, 26, 24.4, 23, 21.45, 19, 16.75, 12.5, and 9.1 kDa).The most prevalent bands
      were that with a molecular weight of 29.3, 26, and 19 kDa. Bands detected were
      common for both species, but protein bands could not distinguish between F.
      hepatica and F. gigantica. The result of PCR for the amplification of the
      selected 28S rDNA fragment with the designed primer set yielded 618 bp long PCR
      products for F. hepatica and F. gigantica. Different band patterns generated
      after digestion of the 618 bp segment by the enzyme AvaII obtained with F.
      hepatica showed segments of the length 529, 62, 27 bp, while with F. gigantica
      322, 269, 27 bp bands were obtained. Genotyping revealed no equivocal results.
      The conventional morphological parameters for species determination of Fasciola
      spp. endemic in Egypt were evaluated versus protein bands characterization and
      genotyping. It was concluded that conventional morphological and metric
      assessments were not useful for differentiation between F. gigantica and F.
      hepatica due to extensive overlap in the relative ranges. Similar conclusion was
      reached concerning protein band characterization where the patterns of protein
      banding were mostly similar. In contrast, genotyping using RFLP-PCR gave
      consistent results and clear differentiation between the two species. Considering
      the implications of proper speciation of endemic parasites on clinical
      evaluation, therapy, epidemiology, and control measures, speciation of parasites
      is currently revised on molecular basis. The presently used molecular tool is
      therefore recommended for further study to help draw a proper map for
      geographical distribution of Fasciola species.

PMID- 22638918
TI  - RNAi silencing of type V collagen in Schistosoma japonicum affects parasite
      morphology, spawning, and hatching.
AB  - Type V collagen is a component of non-cartilaginous tissues and is important in
      the determination of fibril structure and matrix organization, although its
      functions are still poorly understood. In this report, RNA interference (RNAi)
      approaches were used to investigate the effects of knockdown of the schistosome
      type V collagen (SjColV) gene. In this study, three different short interfering
      (si) RNAs targeting different regions of the gene were designed to suppress the
      expression of SjColV in Schistosoma japonicum using a soaking method. By
      establishing controls for measuring off-target RNAi effects, we found that
      different siRNA sequences had different levels of effectiveness. Although all the
      siRNAs tested reduced SjColV transcript levels, the S1 siRNA consistently reduced
      SjColV expression to >99 % of the control. In the following experiments, S1 siRNA
      was adapted to inhibit SjColV expression, and the silencing effects were detected
      by real-time PCR and Western blot. The spawning and egg hatching of parasites
      were calculated, while the worms' morphology was taken by scanning electron
      microscopy. The results show that silencing the expression of SjColV
      significantly affects the spawning and egg hatching of S. japonicum, and it also
      affects the worms' morphology.

PMID- 22638919
TI  - Yolk protein uptake in the oocyte of the Asian tiger mosquito Aedes albopictus
      (Skuse) (Diptera: Culicidae).
AB  - The formation and uptake of the yolk protein in the oocyte of the Asian Tiger,
      Aedes albopictus mosquito was investigated. Light and electron microscopy of the
      ovaries at early resting stage as well as the structural changes associated with
      yolk formation were described 16 h after blood meal. The deposition of the yolk
      protein in the oocyte was correlated with a 15-fold increase in 138-MUm pit-like
      depressions on the oocyte surface. These pits result by invagination of the
      oocyte cell membrane. They have a 20-MUm bristle coat on their convex cytoplasmic
      side and a layer of protein on their concave extraoocyte space. The pits, by
      pinching off from the cell membrane become bristle coat vesicles which carry the
      adsorbed protein into the oocyte. These vesicles lose the coat and then fuse to
      form small crystalline yolk droplets, which subsequently coalesce to form the
      large protein yolk bodies of the mature oocyte. Preliminary radioautographs and
      certain morphological features of the fat body, ovary, and midgut, suggest that
      the midgut is the principal site of the yolk protein synthesis in A. albopictus.

PMID- 22638920
TI  - Evaluation of the insect growth regulator Lufenuron (Match(r)) for control of
      Aedes aegypti by simulated field trials.
AB  - The insect growth regulator, Lufenuron, at concentrations of even multiples of
      LC(90) (determined under laboratory conditions) was tested against the III instar
      larvae of Aedes aegypti under simulated field conditions. For all concentrations
      tested, 100 % mortality of the larvae was observed within 24 h of exposure to
      Lufenuron-treated water. In experiments with LC(90) * 4 Lufenuron concentration
      and where 15 % of water volume was replaced daily, percent mortality of the
      larvae was reduced to 40 % after the 54th day of treatment. Percentage mortality
      of the III instar larvae on the 54th day was higher in water with LC(90) * 6
      concentration than that observed for water with LC(90) * 4 of Lufenuron. In the
      experiments with LC(90) * 4 and LC(90) * 6 concentrations of Lufenuron where 15 %
      of water volume was replaced weekly, larval mortality obtained after the eighth
      week was 68.75 and 88.33 %, respectively. In LC(90) * 4 and LC(90) * 6 of
      Lufenuron-treated stagnant water (without replacement of water), the percent
      mortality of the larvae on the 55th day was 65 and 90 %, respectively.
      Introducing a fresh batch of III instar A. aegypti larvae in the Lufenuron
      treated waters revealed that residual activity of Lufenuron was sustained for 45
      days after the treatment. All these experiments revealed that Lufenuron not only
      affects the prevalence of the A. aegypti larvae but also induces the development
      of abnormal adults.

PMID- 22638921
TI  - Reevaluation of efficacy against nematode parasites and pharmacokinetics of
      topical eprinomectin in cattle.
AB  - A study was conducted to confirm the efficacy of topical eprinomectin against
      nematodes and to evaluate the pharmacokinetics in cattle prevented from having
      physical contact with other cattle and from self-grooming. Sixteen male Brown
      Swiss calves were infected with larvae of recently isolated nematode parasites.
      Inoculation was scheduled so that the nematodes were expected to be adults at the
      time of treatment. Animals were blocked based on pretreatment body weight and
      randomly allocated to the untreated control group or the group treated with
      EPRINEX(r) Pour-On (Merial; 0.5 mg eprinomectin per kilogram body weight). Plasma
      samples were collected prior to and between 1 and 21 days following treatment and
      analysed for eprinomectin (B1a component) concentrations. For parasite recovery,
      identification and counting, animals were humanely euthanized 21 days after
      treatment. Calves treated with eprinomectin had significantly (p < 0.05) fewer
      (>99 % reduction) adult Dictyocaulus viviparus, Bunostomum phlebotomum, Cooperia
      oncophora, Cooperia surnabada, Cooperia punctata, Nematodirus helvetianus,
      Oesophagostomum radiatum, Ostertagia ostertagi, Ostertagia lyrata, and
      Trichostrongylus axei and inhibited fourth-stage Nematodirus and Ostertagia
      larvae than the controls. The main pharmacokinetic parameters of eprinomectin B1a
      were: AUC(inf), 124 +/- 24 day ng/mL; T (1/2), 5.2 +/- 0.9 days; and C (max), 9.7
      +/- 2.2 ng/mL. Individual maximal concentrations were observed 3-7 days after
      treatment. This study confirmed the continued high level of efficacy of topically
      administered eprinomectin against a wide range of recently isolated nematodes. In
      addition, this study demonstrates that oral ingestion is not required to achieve
      adequate exposure for efficacy following topical administration of eprinomectin.

PMID- 22638922
TI  - Conjunctival flap in manual sutureless small-incision cataract surgery: a
      necessity or dogmatic.
AB  - To compare the surgical outcomes of manual sutureless small-incision
      extracapsular cataract surgery (MSICS) with versus without a conjunctival flap
      for the treatment of cataracts. Prospective, randomized comparison of 220
      consecutive patients with visually significant cataracts. Tertiary level eye
      clinic. 220 consecutive patients with cataracts. Patients assigned randomly to
      receive either SICS with a conjunctival flap or without one. Operative time,
      surgical complications, surgically induced astigmatism. Both surgical techniques
      achieved comparable surgical outcomes with comparable complication rates. The
      operative time was markedly less in group without flap (mean duration of 7.67 +/-
      1.45 min) than in group with flap (mean duration of 11.46 +/- 1.69 min) (p value
      <0.001). In the group without a flap intraoperative pupillary miosis was
      significantly greater (p value 0.039) and on postoperative day 1, there were
      greater patients with a subconjunctival bleed involving greater than one quadrant
      of the bulbar conjunctiva (p value <0.0001). Also, post operative conjunctival
      retraction and consequent wound exposure was also significantly higher in this
      group (p value 0.026). However, the rate of other serious complications like any
      postop hyphaema, conjunctival bleb formation, iris prolapse, tunnel stability,
      shallow anterior chamber, post operative uveitis, malpositioned IOL, retinal
      detachment, cystoid macular edema, endophthalmitis were comparable in both. Both
      MSICS with and without a conjunctival flap achieved good surgical outcomes with
      comparable complication rates. But flapless MSICS is significantly faster.
      However it may be associated with higher intraoperative miosis and greater
      postoperative wound exposure.

PMID- 22638923
TI  - Bilateral anterior uveitis in a patient with bacterial meningitis.
AB  - We report a case of bilateral iridocyclitis accompanied by bacterial meningitis
      in an immunocompetent patient. Case report. A 48 year-old healthy female visited
      our hospital with strong headache, fever, bilateral hyperemia, and blurred vision
      in both eyes. A slit-lamp examination revealed moderate cells and flare in the
      anterior chamber of both eyes, with fine keratoprecipitates. There were no
      obvious inflammatory changes in the vitreous, retina, and optic disc of both
      eyes. Elevation of peripheral blood white blood cells, C-reactive protein, and an
      elevated number of cerebrospinal fluid (CSF) cells suggested bacterial
      meningitis. The patient was admitted to our hospital and received intravenous
      antibiotics. Finally, a CSF culture revealed infection with gram-positive rods,
      suspected Listeria monocytogenes, confirming bacterial meningitis. For
      iridocyclitis, we prescribed betamethasone eyedrops and 0.5 % tropicamide
      eyedrops with intravenous adminstration of systemic antibiotics. 3 days later,
      her headache and bilateral hyperemia disappeared. This case is better described
      as sterile reactive uveitis rather than endogenous bacterial endophthalmitis,
      because bilateral anterior uveitis was resolved without chronic uveitis, iris
      atrophy, and vitreous opacity. When clinicians see patients with meningitis and
      bilateral anterior uveitis, sterile reactive uveitis should be considered in the
      differential diagnosis of uveitis.

PMID- 22638924
TI  - Unsuspected femoral hernia in patients with a preoperative diagnosis of recurrent
      inguinal hernia.
AB  - PURPOSE: Small femoral hernias may be difficult to diagnose by physical
      examination and are sometimes identified unexpectedly by laparoscopy. The aim of
      this study was to examine the incidence of unsuspected femoral hernia discovered
      during laparoscopic inguinal hernia repair in two well-defined patient groups.
      METHODS: Patients undergoing laparoscopic transabdominal preperitoneal inguinal
      hernia repair from April 2000 until December 2009 (n = 561) were prospectively
      registered including data on previous hernia operations and identified type of
      hernia during surgery. We included patients whose preoperative diagnosis was
      either bilateral primary inguinal hernia (Primary Group) or recurrent inguinal
      hernia (Recurrent Group). RESULTS: Four hundred and sixty-one (82.2 %) patients
      were included in the study, of whom 211 (45.8 %) was in the Primary Group and 250
      (54.2 %) in the Recurrent Group. The incidence of unsuspected femoral hernia in
      the Recurrent Group [23/250, 9.2 % (95 % CI 5.9-13.5 %)] was significantly higher
      than in the Primary Group [8/211, 3.8 % (95 % CI 1.7-7.3 %)], p = 0.02.
      Furthermore, 38.1 % of women operated on for a recurrent inguinal hernia,
      presented with an unsuspected femoral hernia at surgery as opposed to 6.6 % of
      the men, p = 0.003. CONCLUSION: Unsuspected femoral hernias are more prevalent in
      patients with recurrent hernia than in patients with primary hernia in the
      inguinal region. Femoral hernias may be unrecognized at the primary inguinal
      hernia operation, or the previous inguinal hernia operation may facilitate the
      formation of a femoral hernia. Unsuspected femoral hernias are especially
      frequent in women with recurrent inguinal hernia. In women with a groin hernia, a
      femoral hernia should always be excluded by laparoscopy or by open exploration of
      the preperitoneal space.

PMID- 22638925
TI  - Direct evidence that the N-terminal extensions of the TAP complex act as
      autonomous interaction scaffolds for the assembly of the MHC I peptide-loading
      complex.
AB  - The loading of antigenic peptides onto major histocompatibility complex class I
      (MHC I) molecules is an essential step in the adaptive immune response against
      virally or malignantly transformed cells. The ER-resident peptide-loading complex
      (PLC) consists of the transporter associated with antigen processing (TAP1 and
      TAP2), assembled with the auxiliary factors tapasin and MHC I. Here, we
      demonstrated that the N-terminal extension of each TAP subunit represents an
      autonomous domain, named TMD(0), which is correctly targeted to and inserted into
      the ER membrane. In the absence of coreTAP, each TMD(0) recruits tapasin in a 1:1
      stoichiometry. Although the TMD(0)s lack known ER retention/retrieval signals,
      they are localized to the ER membrane even in tapasin-deficient cells. We
      conclude that the TMD(0)s of TAP form autonomous interaction hubs linking antigen
      translocation into the ER with peptide loading onto MHC I, hence ensuring a major
      function in the integrity of the antigen-processing machinery.

PMID- 22638931
TI  - ['Laryngeal neuropathy' and 'irritable larynx syndrome': synonyms or distinct
      entities?].
AB  - The term 'laryngeal neuropathy' (LN) has first been used in veterinary medicine
      to describe an idiopathic and typically exercise induced inspiratory noise in
      horses.Nowadays, the term is often used in relation with intermittent vocal cord
      pareses in humans. Some authors use the term 'irritable larynx syndrome' (ILS) in
      a similar context. This article reviews the state of knowledge regarding LN and
      ILS and discusses the somewhat confusing terminology.For this systematic review a
      selective literature research in PubMed has been carried out.35 articles were
      found, which report on LN in animals and 17 articles reported on humans. 4 of
      these articles used the term 'irritable larynx syndrome'.Laryngeal neuropathy in
      horses usually affects the left recurrent laryngeal nerve and results in
      decreased vocal cord abduction and an inspiratory roaring or whistling noise,
      particularly during exercise. In dogs LN has been reported to also occur
      bilaterally. In association with humans LN has not been defined clearly in the
      literature. The term ILS on the other hand has only been used in relation to
      humans. The term describes a hypersensitivity of the laryngeal structures towards
      external stimuli, which causes symptoms such as dyspnea or cough among others.
      Sufficient knowledge does not exist for either of the 2 diseases, ILS or LN. As
      of yet, the term LN should not be used in human medicine to describe according
      symptoms of unknown aetiology. The term 'laryngeal movement disorder' seems a lot
      more appropriate. The symptom oriented term irritable larynx syndrome also seems
      suitable to describe laryngeal hypersensitivity appropriately.

PMID- 22638932
TI  - Beneficial lactobacilli: effects on the vaginal tract in a murine experimental
      model.
AB  - Vaginal probiotics containing lactic acid bacteria with activity towards
      pathogenic microorganisms that cause urogenital tract infections have been
      proposed as a valid strategy for their prophylaxis and therapy. A murine
      experimental model was set up to evaluate the colonization capability of
      beneficial human lactobacilli and their effects on the mouse vaginal mucosa and
      innate immune cells. Five Lactobacillus strains were intravaginally inoculated
      into previously estrogenized BALB/c mice. The significance of the effects
      observed in the vaginal tract was determined by analysis of variance using the
      general linear model. The numbers of viable vaginal lactobacilli were
      significantly higher at proestrous-estrous than those at the metaestrous
      diestrous phase and decreased markedly on the days after inoculation.
      Lactobacilli inoculation did not cause cytological or histological modifications
      of the murine vaginal tract. Moreover, the intravaginal administration of
      Lactobacillus salivarius CRL (Centro de Referencia para Lactobacilos culture
      collection) 1328 and Lactobacillus gasseri CRL 1263 did not affect the amounts of
      granulocytes and macrophages present in vaginal washings. In conclusion, the
      results demonstrate that vaginal lactobacilli did not produce adverse effects on
      the murine vaginal tract. Therefore, they could be proposed as safe probiotic
      candidates to promote a balanced microbiota in the urogenital tract.

PMID- 22638926
TI  - Voices from within: gut microbes and the CNS.
AB  - Recent advances in research have greatly increased our understanding of the
      importance of the gut microbiota. Bacterial colonization of the intestine is
      critical to the normal development of many aspects of physiology such as the
      immune and endocrine systems. It is emerging that the influence of the gut
      microbiota also extends to modulation of host neural development. Furthermore,
      the overall balance in composition of the microbiota, together with the influence
      of pivotal species that induce specific responses, can modulate adult neural
      function, peripherally and centrally. Effects of commensal gut bacteria in adult
      animals include protection from the central effects of infection and inflammation
      as well as modulation of normal behavioral responses. There is now robust
      evidence that gut bacteria influence the enteric nervous system, an effect that
      may contribute to afferent signaling to the brain. The vagus nerve has also
      emerged as an important means of communicating signals from gut bacteria to the
      CNS. Further understanding of the mechanisms underlying microbiome-gut-brain
      communication will provide us with new insight into the symbiotic relationship
      between gut microbiota and their mammalian hosts and help us identify the
      potential for microbial-based therapeutic strategies to aid in the treatment of
      mood disorders.

PMID- 22638933
TI  - Electric field exposure triggers and guides formation of pseudopod-like blebs in
      U937 monocytes.
AB  - We describe a new phenomenon of anodotropic pseudopod-like blebbing in U937 cells
      stimulated by nanosecond pulsed electric field (nsPEF). In contrast to "regular,"
      round-shaped blebs, which are often seen in response to cell damage, pseudopod
      like blebs (PLBs) formed as longitudinal membrane protrusions toward anode. PLB
      length could exceed the cell diameter in 2 min of exposure to 60-ns, 10-kV/cm
      pulses delivered at 10-20 Hz. Both PLBs and round-shaped nsPEF-induced blebs
      could be efficiently inhibited by partial isosmotic replacement of bath NaCl for
      a larger solute (sucrose), thereby pointing to the colloid-osmotic water uptake
      as the principal driving force for bleb formation. In contrast to round-shaped
      blebs, PLBs retracted within several minutes after exposure. Cells treated with 1
      nM of the actin polymerization blocker cytochalasin D were unable to form PLBs
      and instead produced stationary, spherical blebs with no elongation or retraction
      capacity. Live cell fluorescent actin tagging showed that during elongation actin
      promptly entered the PLB interior, forming bleb cortex and scaffold, which was
      not seen in stationary blebs. Overall, PLB formation was governed by both passive
      (physicochemical) effects of membrane permeabilization and active cytoskeleton
      assembly in the living cell. To a certain extent, PLB mimics the membrane
      extension in the process of cell migration and can be employed as a nonchemical
      model for studies of cytomechanics, membrane-cytoskeleton interaction and cell
      motility.

PMID- 22638935
TI  - [Value of postoperative radiochemotherapy after completely resected gastric
      cancer not definitive despite negative overall results of the ARTIST trial].

PMID- 22638934
TI  - Comparison of preoperative short-course radiotherapy and long-course
      radiochemotherapy for locally advanced rectal cancer.
AB  - BACKGROUND: The purpose of this work was to perform a single institution
      comparison between preoperative short-course radiotherapy (SC-RT) and long-course
      radiochemotherapy (LC-RCHT) for locally advanced rectal cancer. METHODS: A total
      of 225 patients with clinical stage UICC II-III rectal cancer were treated with
      SC-RT (29 Gy in 10 twice daily fractions followed by immediate surgery; n = 108)
      or LC-RCHT (54 Gy in 28 fractions with simultaneous 5-fluorouracil (5-FU) +/-
      oxaliplatin chemotherapy followed by delayed surgery; n = 117). All patients in
      the LC-RCHT cohort and patients in the SC-RT with pathological UICC stage >= II
      received adjuvant chemotherapy. Before 2004, the standard of care was SC-RT with
      LC-RCHT reserved for patients where downstaging was considered as required for
      sphincter preservation or curative resection. In the later period, SC-RT was
      practiced only for patients unfit for radiochemotherapy. RESULTS: Patients in the
      LC-RCHT cohort had a significantly higher proportion of cT4 tumors, clinical node
      positivity, and lower tumor location. The 5-year local control (LC) and overall
      survival (OS) were 91% and 66% without differences between the SC-RT and LC-RCHT
      groups. Acute toxicity was increased during LC-RCHT (grade >= II 1% vs. 33%) and
      there were no differences in postoperative complications. Severe late toxicity
      grade >= III was increased after SC-RT (12% vs. 3%). Of patients aged >  80
      years, 7 of 7 patients and 4 of 9 patients received curative surgery after SC-RT
      and LC-RCHT, respectively. CONCLUSION: Despite the fact that patients with worse
      prognostic factors were treated with LC-RCHT, there were no significant
      differences in LC and OS between the SC-RT and LC-RCHT group. Age > 80 years was
      identified as a significant risk factor for LC-RCHT and these patients could be
      treated preferably with SC-RT.

PMID- 22638936
TI  - [PET/CT in head and neck squamous cell carcinoma with an unknown primary : 
      Significant diagnostic benefit in a prospective clinical trial].

PMID- 22638937
TI  - [Radiotherapy and re-irradiation of breast cancer patients with brain metastases:
      Survival in the trastuzumab era].

PMID- 22638938
TI  - Glycemic control in diabetic dialysis patients and the burnt-out diabetes
      phenomenon.
AB  - Diabetes mellitus (DM) is the most common cause of end-stage kidney disease and a
      major risk of morbidity and mortality. It is not clear whether medical management
      of DM has any significant beneficial effect on clinical outcomes at the end-stage
      of diabetic nephropathy with full-blown micro- and macro-angiopathic
      complications. Both loss of kidney function and dialysis treatment interfere with
      glucose homeostasis and confound glycemic control. Given the unique nature of
      uremic milieu and dialysis therapy related alterations, there have been some
      debates about reliance on the conventional measures of glycemic control, in
      particular the clinical relevance of hemoglobin A1c and its recommended target
      range of <7 % in diabetic dialysis patients. Moreover, a so-called burnt-out
      diabetes phenomenon has been described, in that many diabetic dialysis patients
      experience frequent hypoglycemic episodes prompting cessation of their anti
      diabetic therapies transiently or even permanently. By reviewing the recent
      literature we argue that the use of A1c for management of diabetic dialysis
      patients should be encouraged if appropriate target ranges specific for these
      patients (e.g. 6 to 8 %) are used. We also argue that "burnt-out diabetes" is a
      true biologic phenomenon and highly prevalent in dialysis patients with
      established history and end-stage diabetic nephropathy and explore the role of
      protein-energy wasting to this end. Similarly, the J- or U-shaped associations
      between A1c or blood glucose concentrations and mortality are likely biologically
      plausible phenomena that should be taken into consideration in the management of
      diabetic dialysis patients to avoid hypoglycemia and its fatal consequences in
      diabetic dialysis patients.

PMID- 22638939
TI  - Pathophysiology of obesity-related renal dysfunction contributes to diabetic
      nephropathy.
AB  - Recent studies have demonstrated the role of insulin resistance in renal injury
      related to obesity, with hyperfiltration leading to glomerulomegaly in a pattern
      similar to that found in diabetic nephropathy. Similarities in the histologic
      patterns of damage from obesity and diabetes point to overlapping mechanisms of
      injury. In this review, we will examine the hormonal mechanisms, signaling
      pathways and injury patterns in renal injury resulting from obesity and attempt
      to draw conclusions on the reasons for these similarities.

PMID- 22638941
TI  - Association between ecological factors and the presence of Rhipicephalus
      (Boophilus) microplus larvae in Puerto Rico.
AB  - A prevalence study was conducted to survey tick larvae populations in Puerto Rico
      (PR), compare the number of infested sites with Rhipicephalus (Boophilus)
      microplus larvae between the wet and dry season, and assess the associations of
      ecologic factors on the presence of R. microplus larvae. Ninety-six sites were
      selected using a GIS-based sampling method. Each site was sampled twice; the
      first sampling was performed during the dry season (March 4-18, 2007) and the
      second sampling during the wet season (August 13-26, 2007). Sites were sampled
      using a tick drag with a 1-m(2) white flannel cloth along a 50-m straight course.
      Only 2 tick species were identified. In the dry season, 15 sites (0.16, 95 % CI =
      0.09-0.24) were identified with R. microplus larvae (n = 606) and 9 sites (0.09,
      95 % CI = 0.04-0.17) with Dermacentor (Anocentor) nitens larvae (n = 779),
      whereas in the wet season 5 sites (0.05, 95 % CI = 0.02-0.12) were identified
      with R. microplus (n = 94), and 5 sites (0.05 %, 95 % CI = 0.02-0.12) with D.
      nitens (n = 275). Difference in the number of infested sites with R. microplus
      was significant (P = 0.031) between the 2 seasons. Factors associated with the
      presence of R. microplus larvae in PR were wind speed of >4.0 km/h (OR = 0.07, 95
      % CI = 0.01-0.63), more than 25 % bushes and shrubs on the site (OR = 11, 95 % CI
      = 1.6-71), and presence of cattle on the site (OR = 26, 95 % CI = 3.4-188).

PMID- 22638940
TI  - Novel targets against retinal angiogenesis in diabetic retinopathy.
AB  - Proliferative diabetic retinopathy (PDR), characterized by pathologic retinal
      angiogenesis, is a major cause of blindness in the USA and globally. Treatments
      targeting vascular endothelial growth factor (VEGF) have emerged as a beneficial
      part of the therapeutic armamentarium for this condition, highlighting the
      utility of identifying and targeting specific pathogenic molecules. There
      continues to be active research into the molecular players regulating retinal
      angiogenesis, including pro-angiogenic factors, anti-angiogenic factors, and
      integrins and matrix proteinases. New insights have been especially prominent
      regarding molecules which regulate specialized endothelial cells called tip
      cells, which play a lead role in endothelial sprouting. Together, these research
      efforts are uncovering new, important molecular regulators of retinal
      angiogenesis, which provide fertile areas for therapeutic exploration. This
      review discusses potential molecular targets, with an emphasis towards newer
      targets.

PMID- 22638942
TI  - Sonography for appendicitis: nonvisualization of the appendix is an indication
      for active clinical observation rather than direct referral for computed
      tomography.
AB  - PURPOSE: To determine the prevalence of perforated and nonperforated appendicitis
      in patients with nonvisualization of the appendix on ultrasound (US) performed
      for suspected appendicitis, and to evaluate the value of CT in these patients.
      METHODS: We analyzed 400 consecutive patients undergoing US for suspected
      appendicitis. Of these patients, 260 had nonvisualization of the appendix, but
      otherwise normal scans. We analyzed the clinical outcome in these patients to
      determine the prevalence of appendicitis, referrals for CT, and the contribution
      of CT in these patients. RESULTS: Of the 400 patients, 140 (35%) had either a
      normal (80 patients, 25%) or an abnormal appendix (60 patients, 15%); 260 (65%)
      had nonvisualization of the appendix. Overall 75 patients had appendicitis
      (18.8%) and 17 (4.3%) had appendicitis with perforation. Of the 260 patients with
      nonvisualization of the appendix, 14 patients (5.4%) had appendicitis and 2 were
      perforated (0.8%). The prevalence of perforated and nonperforated appendicitis in
      this group was significantly lower than the overall group (p < 0.001 and p <
      0.01, respectively). Of these 260 patients, 101 patients (38.8%) had CT within 48
      hours and 79 (78.2%) had normal scans. CONCLUSIONS: Patients with
      nonvisualization of the appendix on US, but otherwise normal scans, are at
      significantly lower risk for appendicitis, either perforated or nonperforated.
      Active clinical observation should be considered in these patients, rather than
      direct referral for CT.

PMID- 22638943
TI  - Oculomotor inhibition of return: how soon is it "recoded" into spatiotopic
      coordinates?
AB  - When, in relation to the execution of an eye movement, does the recoding of
      visual information from retinotopic to spatiotopic coordinates happen? Two
      laboratories seeking to answer this question using oculomotor inhibition of
      return (IOR) have generated different answers: Mathot and Theeuwes (Psychological
      Science 21:1793-1798, 2010) found evidence for the initial coding of IOR to be
      retinotopic, while Pertzov, Zohary, and Avidan (Journal of Neuroscience 30:8882
      8887, 2010) found evidence for spatiotopic IOR at even shorter postsaccadic
      intervals than were tested by Mathot and Theeuwes (Psychological Science 21:1793
      1798, 2010). To resolve this discrepancy, we conducted two experiments that
      combined the methods of the previous two studies while testing as early as
      possible. We found early spatiotopic IOR in both experiments, suggesting that
      visual events, including prior fixations, are typically coded into an abstract,
      allocentric representation of space either before or during eye movements. This
      type of coding enables IOR to encourage orienting toward novelty and,
      consequently, to perform the role of a foraging facilitator.

PMID- 22638944
TI  - Attentional spread in deaf and hearing participants: face and object distractor
      processing under perceptual load.
AB  - The case of human deafness constitutes a unique opportunity to examine possible
      consequences for perceptual processing due to altered sensory experiences. We
      tested whether deaf--in contrast to hearing--individuals are more susceptible to
      visual distraction from peripheral than from central face versus object stimuli.
      The participants were required to classify the gender of a target male or female
      symbol presented either alone (low perceptual load) or together with three filler
      symbols (high perceptual load), while ignoring gender-congruent or -incongruent
      face versus object distractors presented at central or peripheral positions. The
      gender classifications were affected by distractor gender under low, but not
      under high, perceptual load in hearing participants. In contrast, the responses
      of deaf participants were similarly influenced by distractor gender under both
      levels of perceptual load. There was no evidence for generally enhanced attention
      to the visual periphery in deaf individuals. Our results indicate that auditory
      deprivation may result in enhanced attentional capacities under high perceptual
      load.

PMID- 22638945
TI  - [On the way to a new definition of "systemic"?].

PMID- 22638946
TI  - [Systemic therapies--a contribution to psychotherapy integration].
AB  - Some converging lines from neuroscience, neurobiological psychotherapy research,
      process-outcome-research, internet-based change monitoring and the systems and
      complexity sciences actually allow for an open and generic definition of systemic
      therapies. The "family" of systemic therapies as designed here is not restricted
      to the field of psychotherapy. It is a scientifically founded and engaged, bio
      psycho-social multi-level approach to a common or integrative psychotherapy, not
      restricted to a psychotherapeutic confession or exclusively to family or couples
      therapy. A core element of systemic therapy is the support of self-organizing
      processes and the use of data-driven feedback tools. The conclusion goes to a
      modified concept of evidence-based practice and, vice versa, practice-based
      evidence, to an integration of the medical model and the common factors model
      into a self-organization theory of human change processes, and to a list of
      criteria for scientifically based practice in psychotherapy.

PMID- 22638947
TI  - [Sexual orientation and partner-choice of transsexual women and men before gender
      confirming interventions].
AB  - Diverse partner relationship constellations of gender dysphoric women and men
      with different sexual orientations are explored in a sample of 93 persons before
      gender-confirming interventions in persons with female gender identity and male
      body characteristics (MF) and persons with male gender identity and female body
      characteristics (FM). While in both gender groups the majority is single,
      relationship patterns show differences. Apart from working life, FM already live
      predominantly in the new, male gender role and have partners by whom they are
      desired as males. In contrast, only a small proportion of MF already conduct
      their private lives in the new, female gender role, and they often have
      relationships with partners sexually attracted to males and not to their female
      gender identity. The findings indicate a need for differing resources for gender
      dysphoric women and men in the process of a transsexual course of development.

PMID- 22638948
TI  - [Psychometric quality of the "Eating Attitudes Test" (German version EAT-26D) for
      measuring disordered eating in pre-adolescents and proposal for a 13-item short
      version].
AB  - To detect risky eating behavior questionnaires should be economic but at the same
      time they should fulfill the psychometric quality criteria. Available instruments
      are too long for the target group (e. g. EDE-Q, 28 items), restricted on primary
      symptoms (short version of EDI, 23 items) and with minor reliability (e. g. SCOFF
      and WC-Scale, 5 items each). Using the German version of the Eating Attitudes
      Test (EAT-26D, which comprises 26 items) in a community sample of 1 331 11-13
      year old girls and 906 boys from Thuringia, Germany, we measured a internal
      consistency of Cronbachs' Alpha=0.85 for girls and 0.78 for boys. In a principal
      factor analysis, we could replicate the 6-factorial structure of previous
      studies. A confirmatory factor analysis verified the suitability of the EAT-26D
      for both, girls and boys. Reducing the EAT-26D on the 3 core-factors leads to an
      economic 13 item short version with an internal consistency of 0.87 for girls and
      0.80 for boys.

PMID- 22638950
TI  - [Placebo response and placebo effect: mechanisms, mediators, moderators].

PMID- 22638949
TI  - [When are data "too old to rock'n'roll, too young to die"?].

PMID- 22638951
TI  - [Curriculum psychosomatic pain therapy].

PMID- 22638964
TI  - Psychotropic medication claims among religious clergy.
AB  - This study examined psychotropic medication claims in a sample of Protestant
      clergy. It estimated the proportion of clergy in the sample who had a claim for
      psychotropic medication (i.e., anti-depressants and anxiolytics) in 2005 and
      examined associations between sociodemographic characteristics, occupational
      distress and having a claim. Protestant clergy (n = 749) from nine denominations
      completed a mail survey and provided access to their pharmaceutical records.
      Logistic regression models assessed the effect of sociodemographic
      characteristics and occupational distress on having a claim. The descriptive
      analysis revealed that 16 % (95 % Confidence interval [CI] 13.3 %-18.5 %) of the
      clergy in the sample had a claim for psychotropic medication in 2005 and that,
      among clergy who experienced frequent occupational distress, 28 % (95 % CI 17.5 %
      37.5 %) had a claim. The regression analysis found that older clergy, female
      clergy, and those who experienced frequent occupational distress were more likely
      to have a claim. Due to recent demographic changes in the clergy population,
      including the increasing mean age of new clergy and the growing number of female
      clergy, the proportion of clergy having claims for psychotropic medication may
      increase in the coming years. To the best of our knowledge, this is the first
      study to examine the use of psychotropic medication among clergy.

PMID- 22638965
TI  - The hdhA gene encodes a haloacid dehalogenase that is regulated by the LysR-type
      regulator, HdhR, in Sinorhizobium meliloti.
AB  - The plasmid pSymA, in the nitrogen-fixing soil bacterium, Sinorhizobium meliloti,
      carries a 750-bp ORF (SMa1978) designated, hdhA, which encodes a novel
      dehalogenase that can detoxify haloacid compounds, showing a preference for
      haloacetic acids. Purified His-tagged HdhA demonstrated the apparent ability to
      dehalogenate chloroacetic acid and trifluoroacetic acid. In addition, upstream of
      hdhA, a gene encoding a lysR-type transcription regulator denoted, hdhR
      (SMa1979), has been identified to be a transcriptional repressor of hdhA
      expression. In an hdhR knockout mutant, hdhA promoter activity was markedly
      increased. Purified 32-kDa His-tagged HdhR repressed expression of hdhA by
      specifically binding to the promoter region of hdhA, as demonstrated by gel
      mobility shift assay and DNase I foot printing experiments. Moreover, the
      pesticide, pentachlorophenol, was also found to induce hdhA expression via HdhR.
      Site-directed mutants, in which the Cys residues at positions 160 and 192 in HdhR
      were changed to Ser, were constructed. C160S and C192S single mutants showed
      diminished HdhR-mediated repression of hdhA expression, while a C160S:C192S
      double mutant could no longer repress expression of hdhA.

PMID- 22638966
TI  - Comparison of the heterologous expression of Trichoderma reesei endoglucanase II
      and cellobiohydrolase II in the yeasts Pichia pastoris and Yarrowia lipolytica.
AB  - The sequences encoding the genes for endoglucanase II and cellobiohydrolase II
      from the fungus Trichoderma reesei QM9414 were successfully cloned and expressed
      in Yarrowia lipolytica under the control of the POX2 or TEF promoters, and using
      either the native or preproLip2 secretion signals. The expression level of both
      recombinant enzymes was compared with that obtained using Pichia pastoris, under
      the control of the AOX1 promoter to evaluate the utility of Y. lipolytica as a
      host strain for recombinant EGII and CBHII production. Extracellular
      endoglucanase activity was similar between TEF-preoproLip2-eglII expressed in Y.
      lipolytica and P. pastoris induced by 0.5 % (v/v) methanol, but when recombinant
      protein expression in P. pastoris was induced with 3 % (v/v) methanol, the
      activity was increased by about sevenfold. In contrast, the expression level of
      cellobiohydrolase from the TEF-preproLip2-cbhII cassette was higher in Y.
      lipolytica than in P. pastoris. Transformed Y. lipolytica produced up to 15 mg/l
      endoglucanase and 50 mg/l cellobiohydrolase, with the specific activity of both
      proteins being greater than their homologs produced by P. pastoris. Partial
      characterization of recombinant endoglucanase II and cellobiohydrolase II
      expressed in both yeasts revealed their optimum pH and temperature, and their pH
      and temperature stabilities were identical and hyperglycosylation had little
      effect on their enzymatic activity and properties.

PMID- 22638967
TI  - Perception of talker age by young adults with high-functioning autism.
AB  - People with high-functioning Autism (HFA) can accurately identify social
      categories from speech, but they have more difficulty connecting linguistic
      variation in the speech signal to social stereotypes associated with those
      categories. In the current study, the perception and evaluation of talker age by
      young adults with HFA was examined. The participants with HFA performed similarly
      to a typically-developing comparison group in age classification and estimation
      tasks. Moreover, the participants with HFA were able to differentiate among
      talkers of different ages in a language attitudes task and rated older talkers as
      more intelligent than younger talkers. These results suggest that people with HFA
      are able to make reasonable social judgments about talkers based on their speech,
      at least for familiar social categories and personally relevant social attitudes.

PMID- 22638968
TI  - Studies of interaction between insulin and glutathione using electrospray
      ionization mass spectrometry.
AB  - RATIONALE: The interaction of glutathione (GSH) with insulin plays an important
      role in the degradation or regulation of insulin. The characterization of the
      reaction products of GSH and insulin is very important for a proper understanding
      of the mechanism of insulin regulation of GSH. METHODS: Solutions of insulin and
      glutathione were incubated under different experimental conditions in vitro. The
      reaction products were determined by electrospray ionization (ESI) ion trap mass
      spectrometry combined with Fourier transform ion cyclotron resonance (FTICR) mass
      spectrometry. RESULTS: The multi-reaction products were identified, including
      insulin A chain with two intrachain disulfides, insulin B chain with one
      intrachain disulfides, GSH-modified insulin, GSH-modified A chain, GSH-modified B
      chain, aggregates of A chain and B chain, and reduced A chain and B chain. The
      binding site of the B chain with insulin was determined directly by tandem mass
      spectrometry (MS/MS) without enzyme digestion. It was found that the reaction
      between GSH and insulin was pH-, O(2)- and temperature-dependent. CONCLUSIONS:
      The results provide insight into the interaction between GSH and insulin. It has
      also been demonstrated that ESI-MS combined with high-resolution FTICRMS and
      MS/MS provides a powerful tool for screening the reactions of proteins and small
      molecules.

PMID- 22638969
TI  - A surface-activated chemical ionization approach allows quantitative
      phosphorylation analysis of the cyclin-dependent kinase inhibitor Sic1
      phosphorylated on Ser201.
AB  - RATIONALE: Quantitative phosphoproteomics represents a front line for functional
      proteomics and hence for systems biology. Here we present a new application of
      the surface-activated chemical ionization (SACI) technology for quantitative
      phosphoproteomics analysis. The main advantages of SACI-MS technology are high
      sensitivity, quantitative accuracy and matrix effect reduction, which allow
      quantitative estimations. METHODS: A SACI-MS approach was used to investigate the
      quantitative in vivo phosphorylation of the cyclin-dependent kinase inhibitor
      Sic1, a low-abundance protein of Saccharomyces cerevisiae, which is
      phosphorylated on Ser201 by casein kinase 2 (CK2) and compared its
      phosphorylation status in cells growing in two different carbon sources (glucose
      or ethanol). RESULTS: Our relative quantification indicated that the Sic1-Ser201
      phosphorylation level is about 2-fold higher in ethanol- than in glucose-growing
      cells, proportional to the Sic1 protein level. This finding is coherent with
      results of western blot analysis using anti-phospho-Ser201-specific antibody,
      validating the results obtained with this new SACI approach. CONCLUSIONS: The
      findings presented in this paper indicate that the innovative LC/SACI-MS method,
      coupled with immunoprecipitation, is a powerful device to obtain quantitative
      information on the phosphorylation state of low abundance proteins.

PMID- 22638970
TI  - Development and validation of a rapid multi-biomarker liquid
      chromatography/tandem mass spectrometry method to assess human exposure to
      mycotoxins.
AB  - RATIONALE: Mycotoxins regularly occur in food worldwide and pose serious health
      risks to consumers. Since individuals can be exposed to a variety of these toxic
      secondary metabolites of fungi at the same time, there is a demand for proper
      analytical methods to assess human exposure by suitable biomarkers. METHODS: This
      study reports on the development of a liquid chromatography/electrospray
      ionization tandem mass spectrometry (LC/ESI-MS/MS) method for the quantitative
      measurement of 15 mycotoxins and key metabolites in human urine using polarity
      switching. Deoxynivalenol (DON), DON-3-O-glucuronide, DON-15-O-glucuronide
      (D15GlcA), de-epoxy DON, nivalenol (NIV), T-2 toxin, HT-2 toxin, zearalenone,
      zearalenone-14-O-glucuronide, alpha- and beta-zearalenol, fumonisins B(1) and
      B(2) (FB(1), FB(2)), ochratoxin A (OTA) and aflatoxin M(1) (AFM(1)) were
      determined without the need for any cleanup using a rapid and simple dilute and
      shoot approach. RESULTS: Validation was performed in the range of 0.005-40 ug L(
      1) depending on the analyte and expected urinary concentration levels. Apparent
      recoveries between 78 and 119% and interday precisions of 2-17% relative standard
      deviation (RSD) were achieved. The applicability of the method was demonstrated
      by the analysis of urine samples obtained from Cameroon. In naturally
      contaminated urine samples up to six biomarkers of exposure (AFM(1), DON,
      D15GlcA, NIV, FB(1), and OTA) were detected simultaneously. CONCLUSIONS: We
      conclude that the developed LC/MS/MS method is well suited to quantify multiple
      mycotoxin biomarkers in human urine down to the sub-ppb range within 18 min and
      without any prior cleanup. The co-occurrence of several mycotoxins in the
      investigated samples clearly emphasizes the great potential and importance of
      this method to assess exposure of humans and animals to naturally occurring
      mycotoxins.

PMID- 22638971
TI  - Can amino acid carbon isotope ratios distinguish primary producers in a mangrove
      ecosystem?
AB  - RATIONALE: The relative contribution of carbon from terrestrial vs. marine
      primary producers to mangrove-based food webs can be challenging to resolve with
      bulk carbon isotope ratios (delta(13)C). In this study we explore whether
      patterns of delta(13)C values among amino acids (AAs) can provide an additional
      tool for resolving terrestrial and marine origins of carbon. METHODS: Amino acid
      carbon isotope ratios (delta(13)C(AA)) were measured for several terrestrial and
      marine primary producers in a mangrove ecosystem at Spanish Lookout Caye (SLC),
      Belize, using gas chromatography-combustion-isotope ratio mass spectrometry. The
      delta(13)C values of essential amino acids (delta(13)C(EAA)) were measured to
      determine whether they could be used to differentiate terrestrial and marine
      producers using linear discriminant analysis. RESULTS: Marine and terrestrial
      producers had distinct patterns of delta(13)C(EAA) values in addition to their
      differences in bulk delta(13)C values. Microbial mat samples and consumers
      (Crassostrea rhizophorae, Aratus pisonii, Littoraria sp., Lutjanus griseus) were
      most similar to marine producers. Patterns of delta(13)C(EAA) values for
      terrestrial producers were very similar to those described for other terrestrial
      plants. CONCLUSIONS: The findings suggest that delta(13)C(EAA) values may provide
      another tool for estimating the contribution of terrestrial and marine sources to
      detrital foodwebs. Preliminary analyses of consumers indicate significant use of
      aquatic resources, consistent with other studies of mangrove foodwebs.

PMID- 22638972
TI  - Quantitative analysis of pharmaceutical drug distribution in multiple organs by
      imaging mass spectrometry.
AB  - RATIONALE: Recently, the requirement for a quantitative research method using
      imaging mass spectrometry (IMS) to be developed has been discussed. Specifically,
      the simultaneous quantification of a drug in multiple organs by using whole-body
      sections could be insightful for the pharmaceutical industry in the study of drug
      distribution. METHODS: Frozen whole-body sections were obtained from mice
      injected with raclopride, a dopamine D2 receptor selective antagonist, and coated
      with a matrix-assisted laser desorption/ionization (MALDI) matrix compound. The
      whole-body sections were then analyzed using a linear ion trap mass spectrometer
      equipped with a MALDI source. The concentration of raclopride in each tissue was
      determined using liquid chromatography/tandem mass spectrometry (LC/MS/MS).
      RESULTS: The IMS-based signal intensity of raclopride strongly correlated with
      the concentration of the drug in the tissue samples (R=0.94; p <0.001) of six
      different organs. Furthermore, the spatial information obtained by IMS was very
      similar to that obtained by autoradiography, which is a traditional technique
      used for the study of drug distribution. CONCLUSIONS: This study suggests that
      IMS enables the quantitative analysis of drug distribution in multiple organs
      simultaneously. In addition, it enhances ideal drug candidate selection in terms
      of efficient evaluations.

PMID- 22638973
TI  - A survey of useful salt additives in matrix-assisted laser desorption/ionization
      mass spectrometry and tandem mass spectrometry of lipids: introducing nitrates
      for improved analysis.
AB  - RATIONALE: Matrix-assisted laser desorption/ionization (MALDI) is a powerful
      technique for the direct analysis of lipids in complex mixtures and thin tissue
      sections, making it an extremely attractive method for profiling lipids in health
      and disease. Lipids are readily detected as [M+H](+), [M+Na](+) and [M+K](+) ions
      in positive ion MALDI mass spectrometry (MS) experiments. This not only decreases
      sensitivity, but can also lead to overlapping m/z values of the various adducts
      of different lipids. Additives can be used to promote formation of a particular
      adduct, improving sensitivity, reducing spectral complexity and enhancing
      structural characterization in collision-induced dissociation (CID) experiments.
      METHODS: Li(+), Na(+), K(+), Cs(+) and NH(4)(+) cations were considered as a
      range of salt types (acetates, chlorides and nitrates) incorporated into DHB
      matrix solutions at concentrations between 5 and 80 mM. The study was extended to
      evaluate the effect of these additives on CID experiments of a lipid standard,
      after optimization of collision energy parameters. Experiments were performed on
      a hybrid quadrupole time-of-flight (QqTOF) instrument. RESULTS: The systematic
      evaluation of new and existing additives in MALDI-MS and MS/MS of lipids
      demonstrated the importance of additive cation and anion choice and concentration
      for tailoring spectral results. CONCLUSIONS: The recommended choice of additive
      depends on the desired outcomes of the experiment to be performed (MS or MS/MS).
      Nitrates are found to be particularly useful additives for lipid analysis.

PMID- 22638974
TI  - Probing the mechanisms of ambient ionization by laser-induced fluorescence
      spectroscopy.
AB  - The ionization mechanisms of several atmospheric pressure ion sources based on
      desorption and ionization of samples deposited on a surface were studied. Home
      built desorption electrospray ionization (DESI), laserspray ionization (LSI), and
      atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI)
      sources were characterized using low-molecular-weight compounds, in particular
      fluorescent dyes. Detection of the desorbed and ionized species was performed by
      laser-induced fluorescence and ion cyclotron resonance mass spectrometry. The
      dependences of the signal intensities on various experimental parameters were
      studied. The data obtained reveals common features, such as formation of solvated
      species and clusters in the ionization processes, in all of the techniques
      considered.

PMID- 22638975
TI  - Time-dependent intensity changes of free fatty acids detected by matrix-assisted
      laser desorption and ionization time-of-flight mass spectrometry in the presence
      of 1,8-bis-(dimethylamino)naphthalene--a cautionary note.

PMID- 22638976
TI  - Direct analysis of methcathinone from crude reaction mixture by flowing
      atmospheric-pressure afterglow mass spectrometry.

PMID- 22638977
TI  - Establishment of a protocol for large-scale gene expression analyses of laser
      capture microdissected bladder tissue.
AB  - PURPOSE: Lower urinary tract symptoms (LUTS) can be caused by structural and
      functional changes in different compartments of the bladder. To enable extensive
      investigations of individual regions even in small bladder biopsies, we
      established a combination protocol consisting of three molecular techniques:
      laser capture microdissection microscopy (LCM), RNA preamplification and
      quantitative polymerase chain reaction (qPCR). METHODS: Urinary bladders of ten
      mice were resected and frozen immediately or after a delay of 15 min.
      Cryosections were obtained and smooth muscle was isolated using the LCM
      technique. Then, RNA was extracted, including protocols with and without DNase
      digestion as well as with and without the addition of carrier RNA. Extracted RNA
      was either used for reverse transcriptase (RT)-PCR plus qPCR or for a combination
      of RNA preamplification and qPCR. RESULTS: Our data showed that with RNA
      preamplification, 10 MUg cDNA can be regularly generated from 2.5 ng RNA.
      Depending on expression levels, this is sufficient for hundreds of pPCR
      reactions. The efficiency of preamplification, however, was gene-dependent. DNase
      digestion before preamplification lead to lower threshold cycles in qPCR. The use
      of partly degraded RNA for RNA preamplification did not change the results of the
      following qPCR. CONCLUSIONS: RNA preamplification strongly enlarges the spectrum
      of genes to be analyzed in distinct bladder compartments by qPCR. It is an easy
      and reliable method that can be realized with standard laboratory equipment. Our
      protocol may lead in near future to a better understanding of the pathomechanisms
      in LUTS.

PMID- 22638978
TI  - Comparison of two spike areas in bileaflet mechanical valve closing sound.
AB  - We previously reported our development of a wavelet analysis system which
      demonstrates that in vivo bileaflet mechanical valve sound splits into two spikes
      at higher frequency levels and, based on this system, proposed criteria for
      detecting malfunctioning bileaflet valves (MBVs). However, the results of that
      study were only tentative due to the small number of patients with MBVs enrolled
      in the study. Here, we discuss the possibility of new criteria based on the
      scalographic properties of two spikes of bileaflet valve sound. The study cohort
      comprised 12 patients who each received a Carbomedics valve. Based on
      cinefluoroscopy findings, seven valves were classified into a "normal" group, and
      the other five were classified into a "malfunction" group. Five consecutive valve
      sounds for each valve were collected for the wavelet analysis in order to re
      evaluate the previously proposed criteria and to measure both anterior spike area
      (Aa) and posterior spike area (Pa) for calculating the spike area ratio (Aa/Pa).
      The proposed criteria, namely, a single spike or coefficient of variation of
      <0.1120 detected only two of the five malfunctioning valves, as well as one
      normal valve to be malfunctioning. The mean Aa/Pa of all malfunctioning valves
      [2.45 +/- 0.63; 95 % confidence interval (CI) +/-1.01, 95 % confidence limits
      (CL) 1.44-3.46] was significantly higher than that of all normal valves (1.17 +/-
      0.27; 95 % CI +/-0.25, 95 % CL 0.92-1.42). Based on this result, we determined
      the cutoff value of Aa/Pa to be 1.4. The combination of a single spike on the
      scalogram and an Aa/Pa of >1.4 detected more MBVs than previously proposed
      criteria. This combination may represent new criteria for detecting MBVs.

PMID- 22638979
TI  - Acute and chronic effects of sodium tungstate on an aquatic invertebrate (Daphnia
      magna), green alga (Pseudokirchneriella subcapitata), and zebrafish (Danio
      rerio).
AB  - Although aquatic toxicity data exists for tungstate substances, insufficient data
      of high quality and relevancy are available for conducting an adequate risk
      assessment. Therefore, a series of acute and chronic toxicity tests with sodium
      tungstate (Na(2)WO(4)) were conducted on an aquatic invertebrate (Daphnia magna),
      green alga (Pseudokirchneriella subcapitata), and zebrafish (Danio rerio).
      Collectively, the data from these studies suggest that sodium tungstate exhibits
      a relatively low toxicity to these taxa under these test conditions. All studies
      were conducted in the same laboratory under good laboratory practice standards
      using Organisation for Economic Co-operation and Development guidelines with the
      same stock of test material and the same analytical methods. All results are
      reported as mg W/L. The following toxicity values were based on mean measured
      concentrations. For D. magna, the 21 day test no-observable effect concentration
      (NOEC) was 25.9 mg W/L, and the 48-h median effective concentration (EC(50)) from
      the acute test was >95.5 mg W/L (the highest concentration tested). The P.
      subcapitata test yielded an ErC(50) of 31 mg W/L. A 38-day test with zebrafish
      resulted in an NOEC >=5.74 mg W/L with no effects at any concentration. The 96-h
      LC(50) from the acute test with zebrafish was >106 mg W/L. The results of the
      current acute study for daphnids and fish are consistent with published
      literature, whereas the algae results are different from previously reported
      values. Transformation/dissolution (T/D) studies, which were conducted according
      to United Nations Globally Harmonized System of Classification and Labelling of
      Chemicals protocol, confirmed that the WO (4) (-2) anion accounted for most of
      the tungsten in solution. For classification purposes, the algae ecotoxity
      reference value was then compared with T/D data and would not classify Na(2)WO(4)
      as an aquatic toxicant under the European Union Classification, Labelling and
      Packaging scheme.

PMID- 22638980
TI  - Differential effects of the autophagy inhibitors 3-methyladenine and chloroquine
      on spontaneous and TNF-alpha-induced neutrophil apoptosis.
AB  - Autophagy and apoptosis cooperate to modulate cell survival. Neutrophils are
      short-lived cells and apoptosis is considered to be the major mechanism of their
      death. In the present study, we addressed whether autophagy regulates neutrophil
      apoptosis and investigated the effects of autophagy inhibition on apoptosis of
      human neutrophils. We first showed that the established autophagy inhibitors 3
      methyladenine (MA) and chloroquine (CQ) markedly accelerated spontaneous
      neutrophil apoptosis as was evidenced by phosphatidylserine exposure, DNA
      fragmentation and caspase-3 activation. Apoptosis induced by the autophagy
      inhibitors was completely abrogated by a pan-caspase inhibitor Q-VD-OPh.
      Unexpectedly, both MA and CQ significantly delayed neutrophil apoptosis induced
      by TNF-alpha, although the inhibitors did attenuate late pro-survival effect of
      the cytokine. The effect was specific for TNF-alpha because it was not observed
      in the presence of other inflammation-associated cytokines (IL-1beta or IL-8).
      The autophagy inhibitors did not modulate surface expression of TNF-alpha
      receptors in the absence or presence of TNF-alpha. Both MA and CQ induced a
      marked down-regulation of a key anti-apoptotic protein Mcl-1 but did not affect
      significantly the levels of another anti-apoptotic protein Bcl-X(L). Finally, to
      confirm the effects of the pharmacological inhibition of autophagy by a genetic
      approach, we evaluated the consequences of siRNA-mediated autophagy suppression
      in neutrophil-like differentiated HL60 cells. Knockdown of ATG5 in the cells
      resulted in accelerated spontaneous apoptosis but attenuated TNF-alpha-induced
      apoptosis. Together, these data suggest that autophagy regulates neutrophil
      apoptosis in an inflammatory context-dependent manner and mediates the early pro
      apoptotic effect of TNF-alpha in neutrophils.

PMID- 22638981
TI  - [Botulinum toxin in focal hyperhidrosis. An update].
AB  - Eight years after its approval, intralesional injections of botulinum toxin type
      A have become established as an easily performed, highly effective and almost
      complication-free therapeutic option in primary axillary hyperhidrosis. Sweat
      production is decreased to about a sixth of previous amounts, and the effect
      persists for 7 months on average. Restoration of the often significantly impaired
      quality of life has been convincingly documented in large studies. The effect of
      botulinum toxin is based on the inhibition of the release of acetylcholine into
      the synaptic cleft. In addition to this approved use, botulinum toxin is also
      successfully employed in other forms of focal hyperhidrosis, particularly in
      gustatory sweating. However, its use in palmoplantar hyperhidrosis, the second
      most common form of primary hyperhidrosis, is limited because of the pain from
      numerous injections, need for increased doses of the expensive toxin and the
      relatively short effective period of about 4 months. Botulinum toxin type B
      appears to be comparably effective as type A products but is more often
      associated with systemic adverse events.

PMID- 22638983
TI  - HIV-specific immune dysregulation and atherosclerosis.
AB  - HIV + patients face a heightened risk of cardiovascular disease (CVD), which
      cannot be fully explained by traditional risk factors or antiretroviral therapy
      (ART)-related cardiotoxicity. Increasing evidence suggests a significant
      contribution of HIV-specific immune dysregulation to atherosclerosis. HIV
      specific immune dysregulation may have the following atherogenic effects: 1)
      activation of endothelial and immune cells; 2) enhancement of the percentage of
      circulating atherogenic immune cell subsets; and 3) modification of lipid
      function. Efforts are underway to link immune dysregulation markers with
      validated CVD endpoints and to identify genetic predispositions for HIV-induced
      atherogenesis. Moreover, immune suppressants are under evaluation in HIV +
      patients to attempt modification of immune-mediated CVD risk. Taken together,
      these studies will enhance understanding of CVD risk stratification and reduction
      strategies in HIV.

PMID- 22638982
TI  - Hepatitis C and HIV co-infection: new drugs in practice and in the pipeline.
AB  - HCV/HIV coinfection continues to represent a serious health issue with risk of
      liver disease progression and development of hepatocellular carcinoma. Pegylated
      interferon with ribavirin is approved for treatment but results are suboptimal
      and tolerability poor. First-generation HCV protease inhibitors appear to
      significantly improve HCV treatment response in the setting of HIV infection.
      Interactions with HIV protease inhibitors have been documented, but the
      significance of this in terms of adverse reactions and HCV or HIV viral
      breakthrough remains uncertain. Next generation agents hold the promise of even
      better efficacy, with improved dosing schedules and perhaps decreased risk of
      drug:drug interactions.

PMID- 22638984
TI  - Moderate correlation between breath-holding and CO(2) 
      inhalation/hyperventilation methods for transcranial doppler evaluation of
      cerebral vasoreactivity.
AB  - BACKGROUND: Both CO(2) inhalation followed by hyperventilation and breath-holding
      have been utilized to measure cerebral vasomotor reactivity (VMR) but their
      correlation has been poorly studied and understood. METHODS: A retrospective
      study was conducted in 143 subjects (62.6 +/- 15.8 years old, 64% men) with
      transcranial Doppler ultrasonography measurement of mean flow velocity (MFV) at
      baseline, after 30 seconds of breath-holding, and after CO(2) inhalation followed
      by hyperventilation, in the left and right middle cerebral artery. Breath-holding
      index (BHI) was calculated as the percentage of MFV increase from baseline per
      second of apnea. CO(2) inhalation/hyperventilation index (CO(2) /HV) was
      calculated as the percentage of MFV difference between CO(2) inhalation and
      hyperventilation. RESULTS: There were 75 carotid arteries with >70% stenosis or
      occlusion, and 18 middle cerebral arteries with >50% stenosis or occlusion. The
      mean BHI was 0.93 +/- 0.7 and 0.89 +/- 0.6, whereas the mean CO(2) /HV was 61 +/-
      26% and 60 +/- 26%, respectively, on the right and left sides. The correlation
      between BHI and CO(2) /HV was moderate on the right (r = 0.33; p < 0.01) and left
      sides (r = 0.38; p < 0.01). Multivariate linear regression analysis indicated
      that age (p = 0.01) and history of stroke (p = 0.007) were associated
      independently with an impaired VMR on the right as measured by CO(2) /HV. No
      predictors for impaired VMR by CO(2) /HV on the left and by BHI on either side
      were found. CONCLUSIONS: CO(2) /HV and BHI are only moderately correlated.
      Further studies are necessary to determine which method more accurately predicts
      clinical morbidity. (c) 2012 Wiley Periodicals, Inc. J Clin Ultrasound 2012;
      Published online in Wiley Online Library.

PMID- 22638985
TI  - Concreteness effects in bilingual and monolingual word learning.
AB  - Previous studies have demonstrated that bilingualism can facilitate novel-word
      learning. However, the mechanisms behind this bilingual advantage remain unknown.
      Here, we examined whether bilinguals may be more sensitive to semantic
      information associated with the novel words. To that end, we manipulated the
      concreteness of the referent in the word-learning paradigm, since concrete words
      have been shown to activate the semantic system more robustly than abstract words
      do. The results revealed that the bilingual advantage was stronger for novel
      words learned in association with concrete rather than abstract referents. These
      findings suggest that bilingual advantages for word learning may be rooted, at
      least in part, in bilinguals' greater sensitivity to semantic information during
      learning.

PMID- 22638989
TI  - beta-arrestin 2-dependent activation of ERK1/2 is required for ADP-induced
      paxillin phosphorylation at Ser(83)  and microglia chemotaxis.
AB  - Microglia play crucial roles in increased inflammation in the central nervous
      system upon brain injuries and diseases. Extracellular ADP has been reported to
      induce microglia chemotaxis and membrane ruffle formation through P2Y(12)
      receptor. In this study, we examined the role of ERK1/2 activation in ADP-induced
      microglia chemotaxis. ADP stimulation increases the phosphorylation of
      extracellular signal-regulated kinase 1/2 (ERK1/2) and paxillin phosphorylation
      at Tyr(31) and Ser(83) . Inhibition of ERK1/2 significantly inhibited paxillin
      phosphorylation at Ser(83) and the retraction of membrane ruffles, causing
      inefficient chemotaxis. Close examination of dynamics of focal adhesion (FA)
      formation with green fluorescent protein-paxillin revealed that the disassembly
      of FAs in U0126-treated cells was significantly impaired. Depletion of beta
      Arrestin 2 (beta-Arr2) with short hairpin RNA markedly reduced the
      phosphorylation of ERK1/2 and Pax/Ser(83) , indicating that beta-Arr2 is required
      for ERK1/2 activation upon ADP stimulation. A large fraction of phosphorylated
      ERK1/2 and beta-Arr2 were translocated and co-localized at focal contacts in the
      newly forming lamellipodia. Examination of kinetics and rate constant of paxillin
      formation and disassembly revealed that the phosphorylation of paxillin at
      Tyr(31) by c-Src appears to be involved in adhesion formation upon ADP
      stimulation while Ser(83) required for adhesion disassembly.

PMID- 22638990
TI  - [Osteochondrosis dissecans and osteochondral lesions of the talus: clinical and
      biochemical aspects].
AB  - BACKGROUND: The natural course of osteochondral lesions of the talus are varied
      and the disease pattern is not clearly defined. There is an ongoing discussion
      among clinicians concerning the aethiopathology and the correct treatment.
      METHODS: In this article all relevant studies are analysed with regard to
      aetiology, long-term outcome and the different established treatment options.
      Against the background of the current biomechanical understanding, an approach is
      made to this controversially discussed disease pattern utilising our own
      biomechanical laboratory results. RESULTS: The available literature deals with
      longitudinal analyses regarding the natural history of the disease, conservative
      treatment, surgical options like debridement and anterograde drilling, retrograde
      drilling, osteochondral transplantation and autologous chondrocyte
      transplantation (ACT). Biomechanical trials describe high loads in the
      anterolateral parts of the joint. In most of the published studies the average
      age of the patients is around 28 years, younger patients have more favourable
      outcomes compared to older ones. In children the highest rate of spontaneous and
      advantageous course of the disease can be expected. Around 75% of the published
      outcomes relating to surgical therapy are satisfactory while 10% of the patients
      will suffer from osteoarthritis in the long term. CONCLUSION: While the
      aetiopathology of the disease remains unclear, histopathological studies reveal
      subcortical bone necrosis. In 90% of the cases there is an ankle sprain in the
      past medical history although a direct correlation with trauma as exclusive
      trigger is not obvious. A possible approach is an osteochondral fracture in
      combination with an already existing osteonecrosis. A staged treatment regime is
      advised. In asymptomatic cases conservative treatment is advocated independent of
      the stage. Symptomatic patients with Hepple stages I, II and V and intact
      cartilage surface should undergo retrograde drilling in combination with a
      subchondral filling with cancelleous bone. If a cartilage defect is present
      (Hepple stages III, IV, V), an osteochondral transplantation is reasonable. Only
      if the defect zone is >2.5 cm2 should a debridement combined with a
      transplantation of cancellous bone and an ACT be considered. The sole anterograde
      drilling in our opinion should only be performed as an exception.

PMID- 22638992
TI  - Superhydrophobicity in highly fluorinated porous metal-organic frameworks.

PMID- 22638991
TI  - [Plantar fasciitis due to driving lessons?].
AB  - A first league female soccer player presented with the symptoms of a fasciitis
      plantaris of the left foot. After treatment and a training pause she complained
      about the same symptoms in the other foot. In our opinion the reason for this
      dysfunction could be driving lessons. After interrupting the driving lessons in
      combination with pelvic myofascial treatment, the foot complaints were resolved.
      We must therefore assume that unusual actions by an athlete may lead to an
      overuse syndrome. The conclusion for the physicians is that it is obligatory to
      determine all aspects of the athletes activitis, especially those of recreation
      and leisure time also.

PMID- 22638993
TI  - Longitudinal study on health-related quality of life among child and adolescent
      survivors of the 2008 Sichuan earthquake.
AB  - PURPOSE: To longitudinally characterize child survivors' quality of life after a
      massive earthquake in low- and middle-income settings. METHODS: Population-based
      surveys were conducted in the severely affected areas 15 and 36 months after the
      earthquake, using a multi-stage systematic sampling design. RESULTS: A total of
      596 participants were included in the initial assessment, of which 430 were re
      surveyed in the follow-up assessment. For both assessments, means of the PedsQL
      total and subscale scores fell significantly below the general healthy children
      (P < 0.05 for all comparisons). Reduction in PedsQL total scores was observed
      from the initial to the follow-up assessment (82.2 vs. 80.3, P = 0.01). In
      regression analysis, mental health symptoms were examined as the biggest
      contributors for PedsQL scores, and girls and older children were found to report
      lower PedsQL scores than their counterparts. CONCLUSIONS: Health-related quality
      of life among child and adolescent survivors decreased over time. Besides helping
      children with identified risk experiences, attention should also be allocated to
      children without specific traumatic experiences, since the earthquake may have a
      delayed effect on them.

PMID- 22638994
TI  - Health-related quality of life with KDQOL-36 and its association with self
      efficacy and treatment satisfaction in Korean dialysis patients.
AB  - BACKGROUND AND OBJECTIVES: This study was conducted to measure the level of
      health-related quality of life (HRQOL) and to reveal the association of self
      efficacy and treatment satisfaction with it in Korean dialysis patients. DESIGN,
      SETTING, PARTICIPANTS, AND MEASUREMENTS: The study subjects were 237 patients
      receiving either hemodialysis (HD) or peritoneal dialysis (PD) from two
      university hospitals, from February to June in 2010. We investigated HRQOL using
      the Korean version of Kidney Disease Quality of Life Short Form 36 (KDQOL-36),
      and self-efficacy and treatment satisfaction by self-administrative questionnaire
      and their dialysis-related variables by reviewing clinical records. The
      associations of self-efficacy and treatment satisfaction with HRQOL were assessed
      using multiple linear regression analysis. RESULTS: The mean HRQOL results were
      as follows: Physical component score (PCS) was 39.1 +/- 8.5, Mental component
      score (MCS) 44.6 +/- 6.8, symptom/problem list was 67.6 +/- 17.1, effects of
      disease score was 58.5 +/- 19.6, and burden of disease score was 41.1 +/- 28.4.
      Between PD and HD patients, we could find significant difference only in the
      symptom/problem list. After removing confounder's effects by multivariate
      analysis, respectively, treatment goal self-efficacy and treatment management
      self-efficacy were significantly related with all 5 domains, except PCS.
      Treatment satisfaction was significantly related with PCS, MCS, and effects of
      kidney disease. CONCLUSIONS: Patients' self-efficacy and treatment satisfaction
      could influence their HRQOL. Regular and systematic monitoring using KDQOL-36 and
      interventions to increase self-efficacy and treatment satisfaction should be
      considered in dialysis care in Korea.

PMID- 22638995
TI  - Traumatology of the optic nerve and contribution of crystallins to axonal
      regeneration.
AB  - Within a few decades, the repair of long neuronal pathways such as spinal cord
      tracts, the optic nerve or intracerebral tracts has gone from being strongly
      contested to being recognized as a potential clinical challenge. Cut axonal
      stumps within the optic nerve were originally thought to retract and become
      irreversibly necrotic within the injury zone. Optic nerve astrocytes were assumed
      to form a gliotic scar and remodelling of the extracellular matrix to result in a
      forbidden environment for re-growth of axons. Retrograde signals to the ganglion
      cell bodies were considered to prevent anabolism, thus also initiating apoptotic
      death and gliotic repair within the retina. However, increasing evidence suggests
      the reversibility of these regressive processes, as shown by the analysis of
      molecular events at the site of injury and within ganglion cells. We review optic
      nerve repair from the perspective of the proximal axon stump being a major player
      in determining the successful formation of a growth cone. The axonal stump and
      consequently the prospective growth cone, communicates with astrocytes,
      microglial cells and the extracellular matrix via a panoply of molecular tools.
      We initially highlight these aspects on the basis of recent data from numerous
      laboratories. Then, we examine the mechanisms by which an injury-induced growth
      cone can sense its surroundings within the area distal to the injury. Based on
      requirements for successful axonal elongation within the optic nerve, we explore
      the models employed to instigate successful growth cone formation by ganglion
      cell stimulation and optic nerve remodelling, which in turn accelerate growth.
      Ultimately, with regard to the proteomics of regenerating retinal tissue, we
      discuss the discovery of isoforms of crystallins, with crystallin beta-b2
      (crybb2) being clearly upregulated in the regenerating retina. Crystallins are
      produced and used to promote the elongation of growth cones. In vivo and in
      vitro, crystallins beta and gamma additionally promote the growth of axons by
      enhancing the production of ciliary neurotrophic factor (CNTF), indicating that
      they also act on astrocytes to promote axonal regrowth synergistically. These are
      the first data showing that axonal regeneration is related to crybb2 movement
      within neurons and to additional stimulation of CNTF. We demonstrate that
      neuronal crystallins constitute a novel class of neurite-promoting factors that
      probably operate through an autocrine and paracrine mechanism and that they can
      be used in neurodegenerative diseases. Thus, the post-injury fate of neurons
      cannot be seen merely as inevitable but, instead, must be regarded as a challenge
      to shape conditions for initiating growth cone formation to repair the damaged
      optic nerve.

PMID- 22638996
TI  - Cardiovascular disease risk factors: a childhood perspective.
AB  - Atherosclerotic cardiovascular disease (CVD) is one of the leading causes of
      death and disability worldwide including in developing countries like India.
      Indians are known to be predisposed to CVD, which occur almost a decade earlier
      in them. Though these diseases manifest in the middle age and beyond, it is now
      clear that the roots of CVD lie in childhood and adolescence. Many of the
      conventional risk factors of CVD such as high blood pressure, dyslipidemia,
      tobacco use, unhealthy diet and obesity have their beginnings in childhood and
      then track overtime. It is thus important to screen and identify these risk
      factors early and treat them to prevent onset of CVD. Similarly community based
      strategies to prevent onset of these risk factors is imperative to tackle this
      burgeoning public health crisis especially in countries like ours with limited
      resources.

PMID- 22638997
TI  - New mitochondrial DNA mutations in tRNA associated with three severe
      encephalopamyopathic phenotypes: neonatal, infantile, and childhood onset.
AB  - The reported cases showed clinical, biochemical, histopathological, and molecular
      features lending support to the hypothesis of a pathogenic effect of the detected
      mutations. Case 1 was a neonatal presentation who showed multiple mitochondrial
      respiratory chain enzyme defects in muscle associated with a new homoplasmic
      m.5514A > G transition in the tRNA(Trp) gene. Case 2 was a late infantile
      presentation who also showed mitochondrial respiratory chain enzyme deficiencies
      in muscle together with a new m.1643A > G tRNA(Val) mutation in homoplasmy. Case
      3 showed a MERRF phenotype presented in childhood associated with the once
      previously reported m.15923A > G mutation in heteroplasmy in all the tissues
      studied.

PMID- 22638998
TI  - New insights into scaling of fat-free mass to height across children and adults.
AB  - OBJECTIVE: Forbes expressed fat-free mass (FFM, in kg) as the cube of height (H,
      in m): FFM = 10.3 * H(3). Our objective is to examine the potential influence of
      gender and population ancestry on the association between FFM and height.
      METHODS: This is a cross-sectional analysis involving an existing dataset of 279
      healthy subjects (155 males and 124 females) with age 5-59 years and body mass
      index (BMI) 14-28 kg/m(2). FFM was measured by a four-component model as the
      criterion. RESULTS: Nonlinear regression models were fitted: FFM = 10.8 * H(2.95)
      for the males and FFM = 10.1 * H(2.90) for the females. The 95% confidence
      intervals for the exponential coefficients were (2.83, 3.07) for the males and
      (2.72, 3.08) for the females, both containing hypothesized value 3.0. Population
      ancestry adjustment was considered in the H-FFM model. The coefficient of the H
      FFM model for male Asians is smaller than that for male Caucasians (P = 0.006),
      while there is no statistically significant difference among African-Americans,
      Caucasians and Hispanics: 10.6 for the males (10.1 for Asians, 10.8 for African
      Americans, 10.7 for Caucasians and 10.4 for Hispanics) and 9.6 for the females
      (9.3 for Asians, 9.8 for African-Americans, 9.6 for Caucasians and 9.5 for
      Hispanics). Age adjustment was unnecessary for the coefficient of the H-FFM
      model. CONCLUSION: Height is the most important factor contributing to the
      magnitude of FFM across most of the lifespan, though both gender and ancestry
      effects are significant in the H-FFM model. The proposed H-FFM model can be
      further used to develop a mechanistic model to explain why population ancestry,
      gender and age influence the associations between BMI and %Fat.

PMID- 22638999
TI  - Three-year-old child with middle aortic syndrome treated by endovascular stent
      implantation.
AB  - Middle aortic syndrome (MAS) is an extremely rare anomaly and represents both a
      diagnostic and therapeutic challenge, particularly in young children. A case of a
      3.5 year-old child with MAS and arterial hypertension is reported, where owing to
      the patient's young age and the length of the hypoplastic aortic segment,
      surgical correction with end-to-end anastomosis was not feasible. Instead of
      palliative bypass grafting between the thoracic and abdominal aorta, successful
      percutaneous balloon angioplasty and stenting of the lesion was performed with
      the assistance of three-dimensional rotational angiography.

PMID- 22639000
TI  - Ebstein's anomaly and tricuspid valve dysplasia: prognosis after diagnosis in
      utero.
AB  - Tricuspid valve malformation is a rare congenital heart disease. Prenatal
      diagnosis of Ebstein's anomaly (EA) and tricuspid valve dysplasia (TVD) is
      associated with high mortality. There are conflicting reports concerning accurate
      prognostication after diagnosis in utero. The aim of our study was to assess
      prognostic factors based on our experience. We reviewed 37 fetuses between 1984
      and June 2010 comprising 26 cases of EA and 11 cases of TVD. There were 10
      terminations, 5 intrauterine deaths, 8 neonatal deaths, and 14 survivors. We
      found that the major prognostic factor for outcome was the flow pattern through
      the pulmonary valve on the first echocardiogram. Retrograde flow was strongly
      correlated with fetal or neonatal death (p = 8 * 10(-5)), and anterograde flow
      predicted good outcome (p = 8 * 10(-5)). In contrast, cardiothoracic indexes,
      right to left-ventricular ratio, and Celermajer index were not useful prognostic
      markers. The Simpson Andrews Sharland score, which was more complex, was well
      correlated with our series. Flow through the pulmonary valve on the first
      echocardiogram is a simple and excellent prognostic factor when major tricuspid
      valve disease is diagnosed in utero. Fetuses should be monitored throughout
      pregnancy, particularly those with retrograde ductus arteriosus, because several
      hemodynamic factors may worsen the prognosis.

PMID- 22639001
TI  - Transcatheter closure of symptomatic arterial duct in infants younger than 1 year
      old.
AB  - Transcatheter closure is currently considered the first-choice therapeutic option
      in patent arterial duct (AD), although this approach remains challenging in
      younger patients. To evaluate feasibility, safety, and mid-term efficacy of
      percutaneous AD closure using different devices in symptomatic infants <12 months
      old. Among the 483 patients who underwent transcatheter AD closure at our
      institution from April 2000 to January 2012, 69 were <12 months old. All patients
      showed cardiac overload at echocardiography, and 72 % of them were on
      anticongestive therapy. Based on ductal morphology and local anatomy, AD closure
      was attempted using detachable coils in 24 cases (group A) or the Amplatzer Duct
      Occluder (AGA Medical, Golden Valley, MN) device in 45 cases (group B).
      Procedural feasibility was 95.7 % without any difference between groups (95.8 %
      vs. 95.6 %, p = NS) as were fluoroscopy and procedural times. AD size was 2.5 +/-
      0.9 mm, and QP/QS ratio was 2.2 +/- 1.1, with both being significantly higher in
      group B [2.1 +/- 0.9 vs. 2.6 +/- 0.9 mm (p = 0.04) and 1.7 +/- 0.8 vs. 2.5 +/-
      1.2 (p = 0.009), respectively]. Overall complication rate was 1.5 %, without any
      difference between groups, as was the occlusion rate at hospital discharge (86 %)
      and over midterm follow-up (55 +/- 36 months) (98.5 %). Percutaneous closure of
      symptomatic AD might be considered effective and safe in very young infants by
      tailoring the device choice to ductal morphology and local anatomy. In this
      setting, the controlled-release coil option was shown to be as effective as the
      ADO device during midterm follow-up.

PMID- 22639002
TI  - Functional expression and modulation of the L-type Ca2+ current in embryonic
      heart cells.
AB  - Voltage-dependent L-type Ca2+ channels (VDCCs) are critically involved in
      excitation contraction coupling and regulation of the force of contraction. An
      important mechanism contributing to the adaptation of heart function is
      modulation of the L-type Ca2+ current (I(Ca-L)) by hormones of the autonomous
      nervous system. The signaling pathways underlying this regulation in the adult
      heart are well understood. However, VDCC expression and its regulation in the
      embryonic heart are less understood. This report therefore provides a short
      overview of the current knowledge on this topic using embryonic stem cells and
      the mouse as model systems.

PMID- 22639003
TI  - A case of Wolf-Hirschhorn syndrome and hypoplastic left heart syndrome.
AB  - Wolf-Hirschhorn Syndrome (WHS) is a genetic syndrome that includes a typical
      facial appearance, mental retardation, growth delay, seizures, and congenital
      cardiac defects. A deletion of the terminal band of the short arm of chromosome
      4, with a breakpoint at the 4p15 to 4p16 region, is the most common genetic
      mutation causing WHS. Congenital heart disease associated with WHS typically
      includes atrial and ventricular septal defects, though there are a few case
      reports of associated complex congenital heart disease. Here we report a case of
      an infant with a large 4p deletion, with a breakpoint at the 4p12 region, and
      hypoplasic left heart syndrome. We discuss a possible link between the size of
      the chromosomal deletion in WHS and the severity of the cardiac defect.

PMID- 22639004
TI  - Fetal bradycardia and sinus node dysfunction.
AB  - The study reported here is a rare case of fetal sinus bradycardia that evolved
      into symptomatic bradycardia after birth, at which time the implantation of a
      cardiac pacemaker was indicated. Fetal echocardiography was used to diagnose the
      type of cardiac rhythm that caused the intra-uterine bradycardia, which enabled
      the initiation of the appropriate therapy approach and avoided an unnecessary
      interruption of the pregnancy. However, the details of the sinus bradycardia were
      impossible to determine in utero in this case due to sinus node dysfunction.
      After birth, the electrocardiogram results drew attention to a potentially
      unusual cause of sinus bradycardia, and enabled the diagnosis of this rare
      disease in this infant.

PMID- 22639006
TI  - Are adults with congenital heart disease at risk for the development of heart
      failure when feeling depressed? An immunological mechanism.

PMID- 22639005
TI  - Transcatheter closure of acquired left ventricle-to-right atrium shunt: first
      case report in an infant and review of the literature.
AB  - Gerbode defect, a left ventricle to right atrium (LV-RA) communication, is
      usually congenital. Acquired LV-RA communications are rare and only few case
      reports of successful trans-catheter closure have been published though none of
      them were on infants. We hereby report a rare case of LV to RA shunt acquired
      following surgical repair of Tetralogy of Fallot (TOF). The defect was
      successfully closed percutaneously with an Amplatzer duct occluder. This is the
      first reported case of device closure of an acquired Gerbode defect in an infant.

PMID- 22639007
TI  - Treatment strategy and long-term prognosis for patients with esophageal atresia
      and congenital heart diseases.
AB  - A review examined six consecutive cases of patients with esophageal atresia (EA)
      and tracheoesophageal fistula (TEF) who underwent cardiac surgery at the authors'
      institution between 2001 and 2011 for associated complex congenital heart
      diseases. All the patients had a normal karyotype and showed EA with distal TEF.
      In all cases, gastrostomy was the initial surgical intervention. Cardiac surgery
      was performed concurrently with gastrostomy for one patient who had a total
      anomalous pulmonary venous connection with pulmonary venous obstruction. For two
      patients with duct-dependent pulmonary circulation, EA/TEF was corrected in the
      neonatal period, and an aortopulmonary shunt operation was electively performed
      after the first month of life. For two patients with duct-dependent systemic
      circulation, repair of EA/TEF was performed concurrently with gastrostomy,
      followed by palliative cardiac surgery during the neonatal period. For another
      patient without duct-dependent circulation, repair of EA/TEF was performed in the
      neonatal period. No mortality occurred during a median follow-up period of 6.2
      years. However, respiratory complications including severe tracheomalacia for two
      patients, recurrent episodes of respiratory infection for three patients, and
      severe gastroesophageal reflux for five patients caused considerable long-term
      morbidity.

PMID- 22639008
TI  - Univentricular heart with bridging bronchus and sling left pulmonary artery.
AB  - A bridging bronchus (BB) is a rare congenital heart anomaly. Frequently, BB also
      is complicated with congenital cardiac malformation, especially with sling
      (retrotracheal) left pulmonary artery (SLPA). This report presents a patient who
      underwent a Norwood procedure for a complex congenital heart disease with BB and
      SLPA.

PMID- 22639009
TI  - Postnatal outcome in patients with fetal tachycardia.
AB  - The diagnosis and management of prenatal tachyarrhythmias is well established;
      however, the postnatal course and outcomes are not. The purpose of our study was
      to review the natural history of patients with fetal tachycardia, determine the
      incidence of postnatal arrhythmias, and determine whether there are factors to
      predict which fetuses will develop postnatal arrhythmias. A retrospective chart
      review of patients with fetal tachyarrhythmias investigated at British Columbia
      Children's and Women's Hospitals between 1983 and 2010 was conducted. Sixty-nine
      mother-fetus pairs were eligible for the study. Fifty-two had fetal
      supraventricular tachycardia, and 17 had fetal atrial flutter. Conversion to
      sinus rhythm occurred prenatally in 52 % of patients. Postnatal arrhythmia
      occurred in two thirds of patients, with 82 % of those cases occurring within the
      first 48 h of life. Hydrops fetalis, female sex, and lack of conversion to sinus
      rhythm was predictive of postnatal arrhythmia (P = 0.01, P = 0.01, and P = 0.001,
      respectively). Conversion to sinus rhythm prenatally did not predict postnatal
      arrhythmia. Median duration of treatment was 9 months. Two postnatal deaths of
      unknown etiology occurred. Two thirds of all patients with prenatal tachycardia
      will develop postnatal arrhythmia. Prenatal factors that predict postnatal
      arrhythmia include hydrops, sex, and whether or not conversion to sinus rhythm
      occurred prenatally. The majority of patients with postnatal arrhythmia present
      within 48 h of life, which has clinical implications for monitoring. Postnatal
      outcome is generally very good with most patients being weaned off medication in
      6-12 months.

PMID- 22639010
TI  - Educational assortative mating and income inequality in Denmark.
AB  - Many writers have expressed a concern that growing educational assortative mating
      will lead to greater inequality between households in their earnings or income.
      In this article, we examine the relationship between educational assortative
      mating and income inequality in Denmark between 1987 and 2006. Denmark is widely
      known for its low level of income inequality, but the Danish case provides a good
      test of the relationship between educational assortative mating and inequality
      because although income inequality increased over the period we consider,
      educational homogamy declined. Using register data on the exact incomes of the
      whole population, we find that change in assortative mating increased income
      inequality but that these changes were driven by changes in the educational
      distributions of men and women rather than in the propensity for people to choose
      a partner with a given level of education.

PMID- 22639012
TI  - The fetal profile line: a proposal for a sonographic reference line to classify
      forehead and mandible anomalies in the second and third trimester.
AB  - OBJECTIVES: To test the fetal profile (FP) line, defined as the line that passes
      through the anterior border of the mandible and the nasion, as a reference line
      for forehead and mandible anomalies. METHODS: Volumes of 248 normal and 24
      pathological fetuses (16-36 and 19-37 weeks' gestation, respectively) were
      analysed retrospectively. When the FP line passes anteriorly, across or
      posteriorly to the frontal bone, this was defined as 'negative', 'zero' or
      'positive', respectively. When the FP line was positive the distance (F distance)
      between the FP line and the frontal bone was measured. RESULTS: No cases with a
      negative FP line were found in the normal fetuses. Before 27 weeks' gestation the
      FP line was always 'zero' except in one case. After 27 weeks' gestation the FP
      line was 'positive' in up to 25% (F distance (mean, range): 2.8, 2.1-3.6 mm). The
      FP line correctly identified 13 cases with retrognathia, 5 cases with frontal
      bossing and 3 cases with a sloping forehead. CONCLUSION: Although large
      prospective studies are needed, the FP line may be a useful tool to detect second
      trimester profile anomalies such as retrognathia, sloping forehead and frontal
      bossing with the possibility of quantifying the latter.

PMID- 22639011
TI  - Fingolimod--a sphingosine-like molecule inhibits vesicle mobility and secretion
      in astrocytes.
AB  - In the brain, astrocytes signal to the neighboring cells by the release of
      chemical messengers (gliotransmitters) via regulated exocytosis. Recent studies
      uncovered a potential role of signaling lipids in modulation of exocytosis.
      Hence, we investigated whether sphingosine and the structural analog
      fingolimod/FTY720, a recently introduced therapeutic for multiple sclerosis,
      affect (i) intracellular vesicle mobility and (ii) vesicle cargo discharge from
      cultured rat astrocytes. Distinct types of vesicles, peptidergic, glutamatergic,
      and endosomes/lysosomes, were fluorescently prelabeled by cell transfection with
      plasmids encoding atrial natriuretic peptide tagged with mutant green fluorescent
      protein and vesicular glutamate transporter tagged with enhanced green
      fluorescent protein or by LysoTracker staining, respectively. The confocal and
      total internal reflection fluorescence microscopies were used to monitor vesicle
      mobility in the cytoplasm and near the basal plasma membrane, respectively.
      Sphingosine and FTY720, but not the membrane impermeable lipid analogs, dose
      dependently attenuated vesicle mobility in the subcellular regions studied, and
      significantly inhibited stimulated exocytotic peptide and glutamate release. We
      conclude that in astrocytes, cell permeable sphingosine-like lipids affect
      regulated exocytosis by attenuating vesicle mobility, thereby preventing
      effective vesicle access/interaction with the plasma membrane docking/release
      sites.

PMID- 22639013
TI  - Dietary sodium intake and cardiovascular mortality: controversy resolved?
AB  - Universal reduction in sodium intake has long been recommended, largely because
      of its proven ability to lower blood pressure for some. However, multiple
      randomized trials have also demonstrated that similar reductions in sodium
      increase plasma renin activity and aldosterone secretion, insulin resistance,
      sympathetic nerve activity, serum cholesterol and triglyceride levels. Thus, the
      health consequences of reducing sodium cannot be predicted by its impact on any
      single physiologic characteristic but will reflect the net of conflicting
      effects. Some 23 observational studies (>360,000 subjects and >26,000 end points)
      linking sodium intake to cardiovascular outcomes have yielded conflicting
      results. In subjects with average sodium intakes of less than 4.5 grams/day, most
      have found an inverse association of intake with outcome; in subjects with
      average intakes greater than 4.5 grams/day, most reported direct associations.
      Finally, in two, a "J-shaped" relation was detected. In addition, three
      randomized trials have found that heart failure subjects allocated to 1.8 g of
      sodium have significantly increased morbidity and mortality compared with those
      at 2.8 g. At the same time, a randomized study in retired Taiwanese men found
      that allocation to an average intake of 3.8 g improved survival compared with 5.3
      g. Taken together, these data provide strong support for a "J-shaped" relation of
      sodium to cardiovascular outcomes. Sodium intakes above and below the range of
      2.5 to 6.0 grams/day are associated with increased cardiovascular risk. This
      robust body of evidence does not support universal reduction of sodium intake.

PMID- 22639014
TI  - Is it possible to manage hypertension and evaluate therapy without ambulatory
      blood pressure monitoring?
AB  - In the management of patients with hypertension, blood pressure (BP) has been
      traditionally measured in the physician's office. The contribution of ambulatory
      BP monitoring (ABPM) to the management of hypertensive patients has been
      increasingly recognized through clinical and epidemiological research. Ambulatory
      BP monitoring can enhance the ability to detect white-coat or masked
      hypertension, determine the absence of nocturnal dipping status, and evaluate BP
      control in patients on antihypertensive therapy. Recently, the United Kingdom
      National Clinical Guideline Centre published guidelines for the clinical
      management of primary hypertension in adults, recommending the routine use of
      ABPM to make the initial diagnosis of hypertension. While the advantages of ABPM
      are apparent from a clinical perspective, its use should be considered in
      relation to the cost of the equipment, data evaluation, and staff training as
      well as the possible inconvenience to the patient. In this review, we summarize
      the clinical importance of ABPM and discuss the current guidelines for
      establishing the diagnosis of hypertension.

PMID- 22639015
TI  - Vasodilatory mechanisms of beta receptor blockade.
AB  - Beta-blockers are widely prescribed for the treatment of a variety of
      cardiovascular pathologies. Compared to traditional beta-adrenergic antagonists,
      beta-blockers of the new generation exhibit ancillary properties such as
      vasodilation through different mechanisms. This translates into a more favorable
      hemodynamic profile. The relative affinities of beta-adrenoreceptor antagonists
      towards the three beta-adrenoreceptor isotypes matter for predicting their
      functional impact on vasomotor control. This review will focus on the mechanisms
      underlying beta-blocker-evoked vasorelaxation with a specific emphasis on agonist
      properties of beta(3)-adrenergic receptors.

PMID- 22639017
TI  - Metal-free oxidative fluorination of phenols with [18F]fluoride.

PMID- 22639016
TI  - Neurogenic hypertension: revelations from genome-wide gene expression profiling.
AB  - There is now good evidence for a role of the sympathetic nervous system in the
      etiology of essential hypertension in humans. Although genetic variation is
      expected to underlie the elevated sympathetic outflow in this complex polygenic
      condition, only limited information has emerged from classic molecular genetic
      studies. Recently, progress has been made in understanding neurogenic aspects by
      determination of global alterations in gene expression in key brain regions of
      animal models of neurogenic hypertension. Such genome-wide expression studies in
      the hypothalamus and brainstem support roles for factors such as neuronal nitric
      oxide synthase, inflammation and reactive oxygen species. A role for non-coding
      RNAs such as microRNAs, and epigenetic alterations await exploration. Ongoing
      novel approaches should provide a better understanding of the processes
      responsible for the increased sympathetic outflow in animal models, as well as
      essential hypertension in humans. Such information may lead to better therapies
      for neurogenic hypertension in humans.

PMID- 22639024
TI  - [Chemoprevention of prostate cancer - a plea].
AB  - The high disease prevalence, the presentation in older age, a frequently slowly
      progressing course of disease, and high costs make the diagnosis of and therapy
      for prostate cancer a special challenge for urologists. Effective prevention of
      the disease may help to improve some of the problems mentioned above. Two
      randomised, controlled studies have proved that effective chemoprevention of
      prostate cancer is viable using 5alpha-reductase inhibitors (finasteride,
      dutasteride). Furthermore, there is increasing evidence that other compounds, e.
      g., selective oestrogen receptor modulators (SERMs), NSAIDs and statins might
      also be effective. This review investigates potential risks and benefits of
      chemoprevention including a consideration of health economical aspects. The
      authors conclude that the options of chemoprevention should be investigated in an
      open and unbiased way.

PMID- 22639025
TI  - [Sacral neuromodulation as second-line treatment strategy for lower urinary tract
      symptoms of various aetiologies: experience of a German high-volume clinic].
AB  - INTRODUCTION: Lower urinary tract symptoms (LUTS) are a common and multiform
      micturition disorder of various possible origins. Several second-line techniques
      are available in the event of first-line medicinal treatment failure. These
      include the intravesical injection of Botulinum toxin, bladder augmentation and
      sacral neuromodulation (SNM). This study presents current data and results from a
      prospective study of patients with LUTS of various aetiologies. MATERIAL AND
      METHODS: Clinical success was investigated for all patients who underwent SNM for
      LUTS with or without urge incontinence caused by chronic pelvic pain syndrome,
      multiple sclerosis and idiopathic disease between May 2007 and December 2010. The
      preoperatively determined symptoms were compared with current follow-up data.
      Median follow-up time was 11 months (1 - 43). RESULTS: A total of 47 patients
      were indicated for SNM over the investigated period. 80.9 % were female, median
      patient age was 67 years (19 - 84). The testing phase was successful in 38 cases
      (80.9 %) with 9 electrodes being explanted (19.1 %). In the case of idiopathic
      LUTS we could show a statistically significant increase of micturition volume and
      reduction of incontinence pad use. There was no statistically significant
      improvement of any micturition parameter for patients with multiple sclerosis,
      patients with chronic pelvic pain syndrome showed a statistically significant
      reduction of micturition frequency and a subjective improvement of symptoms in 75
      %. CONCLUSIONS: In the selected patient groups SNM is a promising and, in
      experienced hands, a low-complication second-line therapy for the treatment of
      LUTS of idiopathic aetiology. However, the general recommendation of SNM for
      multiple sclerosis and chronic pelvic pain syndrome patients cannot be given on
      the basis of our results. Further prospective, randomised multicentre studies are
      need to further refine the indications for SNM in LUTS of neurogenic and non
      neurogenic origins.

PMID- 22639026
TI  - [Comment to W. Otto et al. Sacral neuromodulation as second-line treatment
      strategy].

PMID- 22639027
TI  - [Supportive options in the treatment of urological tumours].
AB  - An ageing society with a consecutive increase of genitourinary malignancies along
      with remarkable changes in systemic cancer therapy provide the basis for an
      increasing role of supportive measures. While surgical treatment, radiation or
      chemotherapy are undergoing subsequent standardisation, supportive measures are
      still widely used on the basis of personal experience alone. However, effective
      support is the prerequisite for a successful systemic treatment. Within this
      review the most relevant side effects of systemic therapy for urological tumors
      are summarised and the respective therapeutic options are presented in a brief
      but practice-oriented way. The authors have aimed at the consideration of
      evidence-based measures, wherever possible.

PMID- 22639028
TI  - [Metastatic apocrine adenocarcinoma of the penis: cytostatic therapy].
AB  - Metastatic carcinoma of the genital apocrine sweat glands is a rare clinical
      entity. A cytostatic treatment with MTX and bleomycin was performed empirically
      but did not show any satisfactory efficacy. The conversion of the
      chemotherapeutic regime to a tyrosine kinase inhibitor (sunitinib) showed a
      morphologically visible and clinically proven success in terms of a significant
      slowing down of the previous rapid progression of the disease.

PMID- 22639029
TI  - [A bowling ball as the cause of a renal artery embolism].
AB  - A 46-year-old man presented with severe pain in our emergency department. In
      addition he had macrohematuria, the further medical history was inconspicuous.
      The pain showed to be resistant to therapy, therefore we performed a CT scan of
      the abdomen. The CT scan showed a partial embolism of the right renal artery, a
      thrombus of the aorta thoracica as well as partial infarction of the spleen and
      the liver. An immediately initiated therapy with implantation of an aortal stent
      graft for fixation of the thrombus and an Actilyse(r) therapy led to full
      recovery of the patient. Closer questioning of the patient showed that the
      patient undertook an extended abdominal and thoracic muscle training programme by
      letting an eight-kilogram bowling ball fall down onto his abdomen from about 80
      cm height. The diagnosis embolism of the renal artery cannot be made without
      extended diagnostics in the emergency room. A good hint for perfusion disorders
      of the kidney can be obtained with duplex ultrasound. Therapy-resistant pain
      without hydronephrosis and concomitant arrhythmia of the patient can lead to the
      diagnosis. The initiation of an adequate diagnosis and therapy is essential as
      otherwise persisting perfusion disorders of the kidney may occur.

PMID- 22639030
TI  - [Ureterolysis, intraperitonealization of the ureter and ureter-ileum
      interposition in Ormond disease].

PMID- 22639031
TI  - [Retroperitoneal residual tumor resection after chemotherapy of malignant
      testicular cancers].

PMID- 22639033
TI  - Infectious bursal disease: seroprevalence and associated risk factors in major
      poultry rearing areas of Ethiopia.
AB  - The study was conducted in eight districts of Ethiopia with the objectives of
      determining the seroprevalence and associated risk factors of infectious bursal
      disease (IBD). From the total of 2,597 chicken serum samples examined using
      ELISA, 83.1 % were found positive. The highest seroprevalence was found at Mekele
      (90.3 %) while the lowest was recorded at Gondar district (69.8 %). These
      differences among the study areas were statistically significant (p < 0.05).
      Highest seroprevalence was found in crossbreed of chicken (91.4 %) while the
      lowest was recorded in indigenous breed of chicken (81.4 %). This difference was
      statistically significant (p < 0.05) among the three breeds of chickens, but sex
      was not statistically significant (p > 0.05). The seroprevalence of the disease
      was found high in young (<= 8 weeks) age group (86.6 %) while the lowest
      prevalence was recorded in adults (>8 weeks) (72 %). This is also statistically
      significant (p < 0.05) between young and adult age groups. The prevalence of IBD
      in different production system indicated that higher seroprevalence was recorded
      in intensive production system (85.9 %) while the lowest was recorded in
      extensive production system (81.6 %). This difference is also statistically
      significant (p < 0.05).

PMID- 22639034
TI  - Opportunities for conservation and utilisation of local pig breeds in low-input
      production systems in Zimbabwe and South Africa.
AB  - PURPOSE AND METHODS: In situ conservation of pig genetic resources requires
      understanding of the farming systems under which the pigs are kept. The objective
      of the study was to characterise smallholder pig production systems where
      indigenous pigs are kept in order to assess opportunities for in situ
      conservation of these pigs. Factors influencing pig herd sizes, ranking of pigs
      in smallholder production systems, breeds and breed preferences, pig ownership
      patterns, traits preferred by farmers and constraints to production were
      investigated in a survey involving 199 farmers from Chirimhanzu District of
      Zimbabwe, Vhembe, Alfred Nzo and O. R. Tambo Districts of South Africa. RESULTS:
      Income was the major factor influencing most pig production related parameters.
      Most pigs (69.67 %) were owned by women, with most of the women falling into the
      very low income group. Farmers kept pigs for several reasons that were common
      across geographical zones and income groups. The odds of a farmer ranking pigs
      first in the production system depended on the absence of other livestock (P <
      0.05). Farmers in the higher income group tended to mention poor feed resources
      and access to information as constraints (P < 0.05) compared to the very low
      income group. There was preference heterogeneity in the breeds kept and the
      reasons for breed choice across the income groups and geographical zones. Fewer
      farmers in the very low income group (42.62 %) recognised the need to conserve
      local pigs compared to the low income group (80.49 %), the medium income group
      (50.00 %) and the high income group (100.00 %; chi (2) = 19.14; P < 0.001).
      CONCLUSIONS: It was concluded that farmers see value in local pigs and are
      willing to conserve them. In situ conservation programmes are possible and these
      should recognise the role of poor women in conserving and enhancing indigenous
      pig genetic resources.

PMID- 22639035
TI  - Potential for using indigenous pigs in subsistence-oriented and market-oriented
      small-scale farming systems of Southern Africa.
AB  - Indigenous pigs in South Africa are a source of food and economic autonomy for
      people in rural small-scale farming systems. The objective of the study was to
      assess the potential of indigenous pigs for improving communal farmer's
      livelihoods and to inform policy-makers about the conservation of indigenous
      pigs. Data were collected from 186 small-scale subsistence-oriented households
      and 102 small-scale market-oriented households using interviews and direct
      observations. Ninety-three percent of subsistence-oriented and 82 % of market
      oriented households kept indigenous pigs such as Windsnyer, Kolbroek and non
      descript crosses with exotic pigs mainly for selling, consumption and investment.
      Farmers in both production systems named diseases and parasites, followed by feed
      shortages, inbreeding and abortions as major constraints for pig production.
      Diseases and parasites were more likely to be a constraint to pig production in
      subsistence-oriented systems, for households where the head was not staying at
      home and for older farmers. Market-oriented farmers ranked productive traits such
      as fast growth rate, good meat quality and decent litter size as most important
      selection criteria for pig breeding stock, while subsistence-oriented farmers
      ranked good meat quality first, followed by decent growth rate and by low feed
      costs. We conclude that there is high potential for using indigenous pigs in
      subsistence-oriented production systems and for crossbreeding of indigenous pigs
      with imported breeds in market-oriented systems.

PMID- 22639036
TI  - Feeding regime and management of local Lao pigs in Central Lao PDR.
AB  - A survey was carried out in smallholder farming systems in the districts of
      Borrikun, Khamkeuth, and Pakkading, in central Lao People's Democratic Republic,
      to assess the feeding regime and health status of local Lao pigs. In total, 216
      farmers, 72 in each district, were interviewed using a questionnaire. Feed
      samples were collected for nutrient analysis and pen soil samples for mineral
      content determination. Farmers kept sows of native breeds such as Moo Lath, Moo
      Chid, and Moo Hmong. The number of sows per household was low (1.1 +/- 0.1, 1.1
      +/- 0.1, and 1.2 +/- 0.1 in Borrikun, Khamkeuth, and Pakkading, respectively) and
      pigs were mainly fed with rice bran and fresh cassava roots. Daily protein and
      mineral (Calcium, phosphorus, potassium, and sodium) allowances were lower than
      requirements. In all districts, the number of piglets at birth was around seven
      and pre-weaning piglet mortality was around 20 %. The most common causes of
      piglet death, before weaning, were diarrhea, runts, and squashed piglets. Most
      piglets were weaned after 4 months of age, but in the Borrikun and Pakkading
      districts, 11-16 % of households were weaned at <4 months. In all districts, pig
      management was mainly women's responsibility (around 90 %) and most farmers spent
      less than 1 h per day on pig management. A feasible and cheap way to increase
      nutrient supply to local pigs in central Lao People's Democratic Republic would
      be to include more fresh plant material (e.g., thick head, taro) and salt in the
      diet. Information and education on improving pig management should be targeted
      towards women.

PMID- 22639037
TI  - Physiological and haematological indices suggest superior heat tolerance of white
      coloured West African Dwarf sheep in the hot humid tropics.
AB  - Coat colour contributes to physiological adaptation in mammals and mediates
      response to thermal stress. Twenty-four adult West African Dwarf sheep of both
      sexes and with different coat colour types were used in this study. We measured
      rectal temperature (RT), respiratory rate (RR) and pulse rate (PR) before sunrise
      and sunset during the late dry season (January-March) and early rainy season
      (April-June) as well as packed cell volume (PCV), red blood cell (RBC) count,
      white blood cell (WBC) count, plasma sodium (Na(+)) and potassium (K(+)). Animals
      with black coat colour had the highest (P < 0.05) mean values of 38.92 +/- 0.03 
      degrees C, 65.09 +/- 1.06 breaths/min, 81.35 +/- 0.78 beats/min, 1.70 +/- 0.01
      for RT, RR, PR and heat stress index (HSI), respectively, followed by brown
      mouflon and brown with extensive white, while the Badger Face coloured sheep had
      the least mean values. There were significant (P < 0.05) differences between male
      and female sheep for RT, RR, PR and HSI. Season had a significant (P < 0.05)
      effect on RT, RR, PR and HSI. Coat colour and sex also significantly (P < 0.01)
      affected RBC, WBC, Na(+) and K(+). Seasonal variation (P < 0.05) in all the blood
      parameters was observed, with the exception of PCV. Interaction effect of coat
      colour and sex was significant (P < 0.05) on RT and HSI. Correlation coefficients
      among the measured traits ranged from positive to negative values. These results
      indicate that selection of white-coloured sheep to attenuate heat stress is
      desirable in the hot humid tropics.

PMID- 22639038
TI  - Effect of inclusion of tossign (Thymus serrulatus) in concentrate mix
      supplementation on performance and sensory quality of meat of Menz sheep.
AB  - The experiment was conducted to determine feed intake, digestibility, body weight
      change, carcass characteristics, and sensory quality of meat of Menz sheep
      supplemented with a concentrate mix and combinations of different proportions of
      tossign (Thymus serrulatus). Twenty yearling intact male Menz sheep were divided
      according to their initial body weight into five blocks of four animals in a
      randomized block design, and treatments were assigned randomly to each sheep
      within each block. The treatments were a basal diet of hay alone (T1) and
      supplemented with 300 g concentrate mix (T2), 200 g concentrate mix + 100 g
      tossign (T3), and 100 g concentrate mix + 200 g tossign (T4) on a dry matter
      basis. The results indicated that supplementation of tossign together with
      concentrate mix significantly increased (P < 0.001) feed intake and improved DM
      and nutrient digestibility compared to the non-supplemented group.
      Supplementation of tossign with concentrate significantly improved (P < 0.001)
      daily weight gain, feed conversion efficiency, and carcass characteristics of
      sheep compared to the non-supplemented group. Flavor and aroma scores of meat
      samples of sheep in T3 and T4 were significantly higher (P < 0.001) than the
      corresponding values in T1 and T2. The scores for tenderness, juiciness, and
      degree of marbling of meat samples of sheep were significantly higher (P < 0.001)
      in T3 and T4 compared to meat samples of sheep in T1. Inclusion of small amounts
      of tossign as additive in concentrate mix supplementation can improve the sensory
      quality of meat of Menz sheep.

PMID- 22639044
TI  - CA.R.PE.DI.E.M. (Cardio-Renal Pediatric Dialysis Emergency Machine): evolution of
      continuous renal replacement therapies in infants. A personal journey.
AB  - Pedriatric acute kidney injury (AKI) is a well-described clinical syndrome that
      is characterized by a reduction of both the urine output and glomerular
      filtration rate. AKI in critically ill children is typically associated with
      multiple organ dysfunction. A dramatic increase in the incidence of AKI in
      pediatric intensive care units has been observed in the last 10 years.
      Unfortunately, the absence of sufficiently effective preventive and therapeutic
      measures at the present time has limited significant improvements in AKI care.
      Morality in patients with severe AKI remains unacceptably high (>50 %), with
      renal replacement therapy (RRT) remaining the most effective form of support for
      these patients. Despite technological advances during the last 10 years which
      have resulted in the development of the so-called "third-generation dialysis
      machines" that are characterized by the highest level of safety and accuracy, a
      truly pedriatric RRT system has never been developed. Consequently,
      dialysis/hemofiltration in critically ill children is currently performed by
      adapting adult systems to the much smaller pediatric patients. In particular,
      research in this field should focus on children weighing less than 10 kg for whom
      the delivery of RRT is a clinical and technological challenge. We describe here
      the evolution of pediatric RRT during the last 30 years and report in detail on
      the CARPEDIEM project, which has recently been established to finally provide
      neonates and infants with a reliable dialysis machine that is specifically
      designed for this age group.

PMID- 22639043
TI  - Acute kidney injury clinical trial design: old problems, new strategies.
AB  - Apart from supportive dialysis there are no universally accepted interventions in
      acute kidney injury (AKI). We have summarized the outcomes of all published
      randomized, placebo-controlled studies of non-dialysis treatment of AKI. Forty
      nine trials were identified, only one of which was in a paediatric population.
      Sixteen trials had positive outcomes; these trials are not comparable in terms of
      methodology used or outcomes assessed, and they share many of the problems of the
      negative trials. We discuss the flaws in clinical trial design that have
      contributed to poor or uncertain outcomes and propose minimum requirements for
      future trials. In particular, future trials should incorporate biomarkers
      specific to the etiology of the AKI, and treatment should match the phase of
      injury.

PMID- 22639045
TI  - An open-label study to evaluate a single-dose of cinacalcet in pediatric dialysis
      subjects.
AB  - BACKGROUND: There is limited knowledge of the effectiveness and safety profile of
      cinacalcet in pediatric patients with secondary hyperparathyroidism (sHPT)
      treated with dialysis. METHODS: This was an open-label, single-dose study
      conducted on 12 pediatric subjects with chronic kidney disease treated with
      dialysis. Subjects were stratified by four age cohorts and given a single 15-mg
      oral dose of cinacalcet. Multiple blood samples were collected up to 72 h post
      dose for the assessment of serum calcium (Ca), serum intact parathyroid hormone
      (iPTH), and plasma cinacalcet concentrations. RESULTS: Overall, cinacalcet was
      well tolerated with no serious adverse events. Mean (standard deviation)
      percentage change in serum Ca over the first 12 h post-dose was -2.93 % (5.70 %)
      with a nadir of -4.34 % (6.04 %) at 8 h; Ca values returned to baseline by 48 h
      post-dose. Mean percentage change in iPTH over the first 12 h post-dose was 57.94
      % (71.82 %) with a nadir of -35.65 % (55.82 %) at 2 h. There was an inverse
      relationship between peak serum Ca concentration and body surface area (BSA) (r
      (2) = 0.41), although no relationship was found between area under the curve and
      age or BSA. CONCLUSIONS: These data support future analysis to determine the
      therapeutic starting dose of cinacalcet for pediatric patients with sHPT on
      dialysis.

PMID- 22639046
TI  - Differential expression of BNIP family members of BH3-only proteins during the
      development and after axotomy in the rat.
AB  - The BNIPs (BCL2 and adenovirus E1B 19 kDa interacting proteins) are a subfamily
      of BCL2 family proteins typically containing a single BCL2 homology 3 (BH3)
      domain. BNIPs exert important roles in two major degradation processes in cells -
      apoptosis and autophagy. Although it is known that the function of BNIPs is
      transcriptionally regulated under hypoxic conditions in tumors, their regulation
      in the developing brain and neurons following the induction of
      apoptosis/autophagy is largely unknown. In this study, we demonstrate that three
      members of the BNIP family, BNIP1, BNIP3 and BNIP3L, are expressed in the
      developing brain with distinct brain region specificity. BNIP3 mRNA was
      especially enriched in the entorhinal cortex, raising a possibility that it may
      have additional biological functions in addition to its apoptotic and autophagic
      functions. Following starvation-induced autophagy induction, BNIP1 mRNA was
      selectively increased in cultured neurons. However, the apoptogenic chemical
      staurosporine failed to modulate the expression of BNIPs, which is in contrast to
      the marked induction of all BNIPs by glucose-oxygen deprivation. Finally,
      neonatal nerve axotomy, which triggers apoptosis in motoneurons, selectively
      enhanced BNIP3 mRNA expression. Collectively, these results suggest that the
      expression of BNIPs is differentially regulated depending on the stimuli, and
      BNIPs may exert unique biological functions.

PMID- 22639049
TI  - First reported case of hemoglobin lansing in Asia detected by false low oxygen
      saturation on pulse oximetry.

PMID- 22639047
TI  - Protein kinase Calpha protects against multidrug resistance in human colon cancer
      cells.
AB  - Multidrug resistance is the phenomenon by which, after exposure to a single
      chemotherapeutic agent, cancer cells evade the agent's cytotoxic effects as well
      as become resistant to several classes of diverse drugs. ATP-binding cassette
      (ABC) transporters are a family of transporter proteins that contribute to drug
      resistance via a n ATP - dependent drug efflux pump. P-glycoprotein (P-gp) is a
      prominent ABC superfamily protein encoded by the mdr gene which has the ability
      to mediate the cellular extrusion of xenobiotics and anticancer drugs from tumor
      cells. Exclusively expressed P-gp cells from the human colon cancer HCT15/DOX
      line showed resistance to doxorubicin while parental HCT15 cells treated with
      doxorubicin displayed typical signs of apoptosis. In order to verify the
      hypothesis that expression of MDR is controlled in part, by protein kinase C
      (PKC), expression patterns of different PKC isoforms were examined in both cell
      lines. Of the PKC isoforms evaluated, the membrane translocation and expression
      levels of PKCalpha were strikingly increased in HCT15/DOX cells. PKCalpha
      reversed doxorubicin-induced apoptosis through the scavenging of ROS as well as
      inhibition of PARP cleavage. In addition, inhibition of PKCalpha with Go6976, a
      specific inhibitor of classical PKC, led to reduced MDR expression and increased
      doxorubicin-induced apoptosis. Knockdown of PKCalpha by siRNA diminished the
      protective effects of PKCalpha for doxorubicin-induced apoptosis. These results
      suggested that over-expression and activity of PKCalpha is closely associated
      with the regulation of the MDR phenotype in human colon cancer HCT15 cells and
      provided insight into a new strategy for inhibiting doxorubicin resistance in
      human cancers.

PMID- 22639050
TI  - Molecular analysis of afibrinogenemic mutations caused by a homozygous FGA1238 bp
      deletion, and a compound heterozygous FGA1238 bp deletion and novel FGA c.54+3A>C
      substitution.
AB  - We identified two afibrinogenemic girls in two Japanese families and performed
      molecular analysis to clarify the mechanisms of fibrinogen defects. Genetic
      analyses were performed by PCR amplification of the fibrinogen gene and DNA
      sequence analysis. To analyze the mechanisms of mature fibrinogen defects in
      plasma, we cloned minigenes from the proposita's PCR-amplified DNA, transfected
      them into CHO cells, and sequenced the cDNA amplified with the RT reaction
      followed by PCR. Sequence analyses indicated that one was caused by a homozygous
      1238 bp deletion of the fibrinogen Aalpha-chain gene (FGADelta1238) and the other
      was a compound heterozygous FGADelta1238 and novel FGA c.54+3A>C substitution.
      The minigene corresponding to FGADelta1238 generates two aberrant mRNAs, both of
      which may induce a frameshift and terminate prematurely. In contrast, the
      minigene corresponding to FGA c.54+3A>C generates two aberrant mRNAs, one of
      which may induce a frameshift and terminate prematurely, and the other uses a
      cryptic 5' splice site in exon 1, resulting in the deletion of six amino acids in
      signal peptides. Molecular analyses of both genetic variants suggest that the
      lack of a mature Aalpha-chain, impaired assembly, and/or secretion of the
      fibrinogen molecule may lead to afibrinogenemia.

PMID- 22639052
TI  - Elevation of pulmonary artery pressure as a complication of nilotinib therapy for
      chronic myeloid leukemia.
AB  - We present the case of a 72-year-old male with chronic phase myeloid leukemia.
      Elevation of the pulmonary artery pressure due to nilotinib therapy was noted.
      This effect on pulmonary artery pressure was nilotinib dose dependent.

PMID- 22639051
TI  - High serum carbohydrate antigen-125 (CA-125) level predicts poor outcome in
      patients with follicular lymphoma independently of the FLIPI score.
AB  - Carbohydrate antigen-125 (CA-125) was established as a prognostic marker in
      cancer, especially in ovarian carcinoma. Many recent studies have also reported
      on the prognostic significance of CA-125 in patients with different types of
      lymphoma, but only a few studies have been carried out in patients treated with
      rituximab or high-dose therapy. The prognostic impact of CA-125 on a large cohort
      of patients with follicular lymphoma (FL) has not been studied. This study
      analyzed the prognostic significance of CA-125 levels in 116 prospectively
      enrolled patients with previously untreated FL. It showed that the CA-125 level
      at the time of treatment initiation correlates with the clinical stage, number of
      involved nodal areas, bulky disease, hemoglobin level, beta-2 microglobulin
      level, and lactate dehydrogenase level. Patients with CA-125 >35 U/mL had
      significantly shorter progression-free (p < 0.001) and overall (p = 0.025)
      survival rates. Cox regression analysis identified high CA-125 levels as a
      prognostic factor for overall (HR 3.04, p = 0.05) and progression-free (HR 3.55,
      p < 0.001) survival rates independent of FLIPI score variables. CA-125 levels may
      help to refine risk assessment in the modern immunotherapy era.

PMID- 22639053
TI  - Randomized comparison of fixed-schedule versus response-oriented individualized
      induction therapy and use of ubenimex during and after consolidation therapy for
      elderly patients with acute myeloid leukemia: the JALSG GML200 Study.
AB  - We conducted a multicenter prospective randomized study to compare a fixed
      scheduled induction therapy with a response-oriented individualized induction
      therapy for elderly patients with acute myeloid leukemia (AML). Newly diagnosed
      AML patients, aged between 65 and 80, were randomly assigned to receive fixed or
      individualized induction. Both groups received daunorubicin (DNR) 40 mg/m(2) for
      3 days and behenoyl cytarabine (BHAC) 200 mg/m(2) for 8 days. In the
      individualized group, bone marrow biopsy was done on days 8 and 10, and according
      to the cellularity and blast ratio, the patients received additional DNR and BHAC
      for two to four more days. All patients achieving complete remission (CR) were
      randomized a second time to determine whether they would receive ubenimex. CR was
      obtained in 60.1 % of the fixed group and 63.6 % of the individualized group.
      Predicted 4-year relapse-free survival (RFS) was 9 % for the fixed group and 18 %
      for the individualized group. There were no statistically significant differences
      in CR and RFS between the fixed and individualized groups. In the ubenimex group,
      prolonged RFS was observed. Notably, gender was a prognostic factor in this
      study, as 102 female patients had a significantly higher CR rate (72.5 vs. 54.3
      %, p = 0.0048) and better OS (24 vs. 14 % at 4 years, p = 0.018), compared with
      140 male patients.

PMID- 22639054
TI  - Guest editorial: the contribution of pluripotent stem cells to blood cells.

PMID- 22639055
TI  - Clinical relevance of the association of interferon alfa to imatinib in chronic
      myeloid leukemia therapy.

PMID- 22639056
TI  - Influence of body fat and level of physical activity on rate-pressure product at
      rest in preschool children.
AB  - OBJECTIVE: The rate-pressure product (RPP) has strong correlation with the
      maximal oxygen consumption and is an indicator of myocardium stress being
      considered as the best indirect method to measure myocardial oxygen consumption.
      However, to the best of our knowledge, no studies have addressed in preschool
      children. The aim of this study was to analyze the influence of percentage of
      body fat (%BF) and physical activity (PA) patterns on RPP at Rest (RPPrest) as a
      marker of cardiac load in Preschool children. METHODS: The study comprised 593
      preschool children aged 3-6 years-old. Heart rate (HR), systolic (SBP), and
      diastolic (DBP) blood pressure were taken at rest. The RPP was then calculated.
      The %BF was estimated from four skinfolds thicknesses and PA was assessed during
      7 consecutive days by accelerometry. RESULTS: Our data showed that only %BF (P <=
      0.001) and vigorous PA (P <= 0.05) contributed significantly toward RPPrest
      variation. However, the multivariate analysis showed that only %BF (P <= 0.05)
      had a significant influence on RPPrest variation. CONCLUSION: These findings
      suggest that on preschoolers there is an association between RPP at rest and %BF.

PMID- 22639057
TI  - Aicardi-Goutieres syndrome with emphasis on sonographic features in infancy.
AB  - BACKGROUND: Aicardi-Goutieres syndrome (AGS) is a severe familial, mostly
      autosomal recessive encephalopathy, first described in 1984. The clinical picture
      and genetic abnormalities are heterogeneous. US findings in AGS have thus far not
      been systematically described. OBJECTIVE: The purpose of this study was to
      analyse sonographic features in AGS and to compare them to CT/MRI. MATERIALS AND
      METHODS: Four male infants with AGS, two brothers, underwent imaging between the
      ages of 4 weeks and 6 months. RESULTS: Sonographically isolated mineralization of
      lenticulostriate vessels, dilatation of the lateral ventricles, subependymal
      cysts, and diffuse and focal hyperechogenicity of the periventricular white
      matter and basal ganglia, respectively, were the abnormal findings, that may be
      present even before the development of major neurological symptoms. CONCLUSION:
      Early cranial US is able to visualize the whole spectrum of cerebral anomalies in
      AGS: calcifying microangiopathy, white matter disease and unusual subependymal
      cysts. The imaging pattern is similar to that of congenital viral infection of
      the central nervous system, which may mislead the genetic counseling.

PMID- 22639059
TI  - [Musculoskeletal infections in the era of multiresistant pathogens].
AB  - The burden of musculoskeletal infections is permanently growing. A probable
      explanation for this development could be the increasing number of elderly people
      undergoing extensive surgery using implants and prosthetic devices while having
      more significant comorbidities (e.g. cardiovascular, metabolic and malignant).
      However, a relative reduction of acute (hematogenous) osteomyelitis compared to
      the occurrence of much more complex situations, such as diabetic foot syndrome or
      chronic osteitis and prosthetic implant infections is being observed. This poses
      new challenges for the clinician in managing these patients. Furthermore, there
      is the evolving threat of antimicrobial resistance as well as the increasing
      amount of infections with Gram-negative pathogens. Several aspects have to be
      considered for successful management of musculoskeletal infections: the site of
      infection and feasibility of local surgical treatment, the effectiveness of
      antimicrobial treatment, the inclusion of comorbidities and their specific
      treatment in an advanced therapeutic concept as well as the interdisciplinary
      approach led by surgeons and infectious disease specialists.

PMID- 22639062
TI  - Evidence for an effect of ACE inhibitors on cancer cachexia.

PMID- 22639060
TI  - Phosphorylated olig1 localizes to the cytosol of oligodendrocytes and promotes
      membrane expansion and maturation.
AB  - Oligodendroglial cells undergo rapid transcriptional and dynamic morphological
      transformation in order to effectively myelinate neuronal axons. Olig1, a basic
      helix-loop-helix transcription factor, functions to promote the transcription of
      myelin-specific genes and promotes differentiation and (re)myelination. While the
      role for nuclear Olig1 is well established, the function for cytoplasmic Olig1
      remains uncertain. We observe that translocation of Olig1 into the cytosol highly
      correlates with differentiation of oligodendrocytes both invivo and invitro. By
      enforcing expression of a nuclear-specific form of Olig1 into OPCs in a null
      Olig1 background, we demonstrate that nuclear Olig1 is sufficient to facilitate
      MBP expression, but with greatly diminished membrane volume and area. We
      demonstrate that serine 138 in the helix-loop-helix domain of Olig1 is
      phosphorylated and that this form resides in the cytosol. Mutating serine 138 to
      alanine restricts Olig1 to the nucleus, facilitating MBP expression but limiting
      membrane expansion. However, a serine to aspartic acid mutation results in the
      cytoplasmic localization of Olig1 enhancing membrane expansion. Our results
      suggest a novel role for a phosphorylated cytosolic Olig1 in membrane expansion
      and maturation of oligodendrocytes.

PMID- 22639061
TI  - Developmental expression of lineage specific genes in porcine embryos of
      different origins.
AB  - PURPOSE: This study compared the expression of genes involved in pluripotency,
      segregation of inner cell mass (ICM) and trophectoderm (TE), and primitive
      endoderm (PE) formation in porcine embryos produced by in vitro fertilization
      (IVF), parthenogenetic activation (PA), and nuclear transfer (NT) using either
      fetal fibroblasts (FF-NT) or mesenchymal stem cells (MSC-NT). METHODS: Blastocyst
      formation and total cell number were analyzed. The expression patterns of
      transcripts, including SRY-related HMG-box gene 2 (SOX2), reduced expression gene
      1 (REX1/ZFP42), LIN28, caudal type homeobox 2 (CDX2), TEA domain family member 4
      (TEAD4), integrin beta 1 (ITGB1) and GATA6 were assessed at the 4-8 cell and
      blastocyst stage embryos by real-time PCR. RESULTS: Developmental rates to
      blastocyst stage and total cell number were higher in IVF and PA embryos than in
      NT embryos. But MSC-NT embryos had increased blastocyst formation and higher
      total cell number compared to FF-NT embryos. The relative expressions of
      transcripts were higher in blastocysts than in 4-8 cell stage embryos. The mRNA
      expression levels of SOX2 and REX1 were largely similar in embryos of different
      origins. However, the genes such as LIN28, CDX2, TEAD4, ITGB1 and GATA6 showed
      the differential expression pattern in PA and NT embryos compared to IVF embryos.
      Importantly, the transcript levels in MSC-NT embryos were relatively less
      variable to IVF than those in FF-NT embryos. CONCLUSION: MSCs seem to be better
      donors for porcine NT as they improved the developmental competency, and
      influenced the expression pattern of genes quite similar with IVF embryos than
      that of FFs.

PMID- 22639063
TI  - Diversity of Apis mellifera subspecies from Turkey revealed by sequence analysis
      of mitochondrial 16s rDNA region.
AB  - Mitochondrial DNA sequence variation can be used to infer honeybee evolutionary
      relationships. In this study, DNA sequence diversity of the mitochondrial 16s
      rDNA region was investigated in 112 honeybees from 15 populations in Turkey,
      which is mainly populated with Apis mellifera anatoliaca, A. m. caucasica, and A.
      m. meda. The study revealed 11 haplotypes for this segment, with 13 variable
      sites and nine parsimony informative sites. The haplotypes were not discriminated
      according to their geographical locations in a neighbor-joining dendrogram based
      on 16s rDNA sequences available in Genbank, but all the haplotypes obtained in
      this study are clustered with published haplotypes such as A. mellifera TAS
      (AF214666) and A. m. ligustica (EF116868) and with some unpublished Genbank
      records (HQ318928, HQ318934, and HQ318938). This study expands the knowledge of
      the mitochondrial 16s rDNA region, and it presents the first comprehensive
      sequence analysis of this region in Turkish honeybees.

PMID- 22639064
TI  - Noble-metal nanocrystals with concave surfaces: synthesis and applications.
AB  - Metal nanocrystals with concave surfaces are interesting for a wide variety of
      applications that are related to catalysis, plasmonics, and surface-enhanced
      spectroscopy. This interest arises from their high-index facets, surface
      cavities, and sharp corners/edges. Two major challenges are associated with this
      novel class of nanocrystals: 1) how to generate a concave surface with negative
      curvature, which is not favored by thermodynamics owing to its higher energy than
      the convex counterpart; and 2) how to stabilize the morphology of a nanocrystal
      with concave structures on the surface. Recently, a number of different
      procedures have been developed for the synthesis of noble-metal nanocrystals with
      concave surfaces. This Review provides a brief account of these developments,
      with the aim of offering new insights into the growth mechanisms. We focus on
      methods based on two general strategies: 1) site-specific dissolution through
      etching and galvanic replacement; and 2) directionally controlled overgrowth by
      facet-selective capping, kinetic control, and template-directed epitaxy. Their
      enhanced catalytic and electrocatalytic properties are also described.

PMID- 22639065
TI  - Q Fever endocarditis: does serology predict outcome?
AB  - Q fever is an ubiquitous zoonosis caused by Coxiella burneti, an intracellular
      bacterium that can produce acute or chronic infections in humans. These forms are
      characterized by different evolution, serological profile and treatment that must
      be very long to achieve a cure in chronic forms. However, the serological profile
      for diagnosis and the real value of serology for predicting outcome are
      controversial, and management dilemmas for many patients with Q fever infection
      are continuously emerging. In this article, we describe in a comprehensive manner
      the different clinical presentations of the disease, making a critical overview
      of the evidence for serological predictions. We also take a broad view of new
      available diagnostic techniques and finally, we give recommendations for
      treatment.

PMID- 22639067
TI  - Maternal IgM antibody status in confirmed fetal cytomegalovirus infection
      detected by sonographic signs.
AB  - OBJECTIVE: To evaluate the value of maternal IgM to cytomegalovirus (CMV) as a
      predictive factor of fetal infection in fetuses with sonographic markers.
      METHODS: Observational study (2006-2011) including a consecutive series of 19
      fetuses with sonographic markers of fetal infection and confirmed infection by
      positive CMV-DNA in amniotic fluid or fetal blood. We evaluated the status of
      maternal CMV IgM at the time of sonographic suspicion. RESULTS: During this 6
      year study period, CMV infection was diagnosed in 19 fetuses from 18 pregnancies,
      including 16 singletons, both twins of a monochorionic diamniotic pregnancy and
      one twin of a dichorionic pregnancy. Sonographic suspicion was established on the
      basis of one or more of the following: brain abnormalities (14), fetal hydrops
      (4), hyperechogenic bowel (4), pericardial effusion (1), cardiomegaly (1),
      oligoanhydramnios (4), and placentomegaly (2). Maternal IgG antibodies were
      positive in all cases but maternal IgM antibodies were negative in 56% of
      pregnancies. Five of the 10 pregnancies with negative maternal IgM were diagnosed
      in the second trimester and five in the third trimester. CONCLUSION: In around
      half of fetuses with confirmed CMV infection ascertained by sonographic markers,
      maternal IgM antibodies are negative and should therefore not be used as a
      diagnostic parameter.

PMID- 22639068
TI  - Renal biomarkers for assessment of kidney function in renal transplant
      recipients: how do they compare?
AB  - Accurate assessment of renal function is of key importance, given its prognostic
      value. However, gold standard measures are cumbersome, and serum creatinine
      itself is an insensitive predictor, especially in renal transplant recipients.
      Though GFR-estimating formulae have been relied upon, they do have their own
      limitations. Nevertheless, renal biomarkers such as neutrophil gelatinase
      associated lipocalin (NGAL) and cystatin C, among others, are now emerging as
      potentially useful indicators of GFR. We aimed to evaluate the diagnostic
      performance of NGAL versus cystatin C and eGFR using CKD-EPI, MDRD and cystatin C
      in renal transplant recipients and non-transplant CKD patients. We found a
      significant correlation between NGAL, serum creatinine, cystatin C and eGFR. The
      latter parameters were also strong predictors of serum NGAL levels. However,
      performance of NGAL, based on receiver operating characteristic curves, was
      inferior to that of the reference tests. It appears that in renal transplant
      recipients NGAL correlates well with cystatin C and eGFR, most strongly with
      cystatin-based formula. Though this suggests potential use of NGAL as a screening
      test, its weaker diagnostic performance raises some concern about its clinical
      usefulness. Larger studies are needed to explore this further.

PMID- 22639070
TI  - Revisiting social recognition systems in invertebrates.
AB  - Since the 1970s, the ability of some invertebrate species to recognize individual
      conspecifics has attracted increased scientific interest. However, there is still
      confusion in the literature, possibly due to the lack of unambiguous criteria for
      classifying social recognition in its different forms. Here, we synthesize the
      results of studies on invertebrates and provide a framework with the purpose of
      identifying research needs and directions for future investigations. Following in
      part Sherman et al.'s (Behavioural ecology: an evolutionary approach. Blackwell
      Science, Oxford, pp 69-96, 1997) definition of 'recognition systems' and Tibbetts
      and Dale's (Trends Ecol Evol 22:529-537, 2007) classification of 'individual
      recognition,' we first discuss different case studies that exemplify the
      categories of 'familiar recognition' and 'class-level recognition.' Then, through
      the analysis of the invertebrate literature, we illustrate eight key properties
      that characterize 'true individual recognition' systems. We are confident that
      the proposed framework will provide opportunities for exciting discoveries of the
      cognitive abilities in invertebrates.

PMID- 22639066
TI  - The Pathogenesis and Prevention of Encephalitis due to Human Enterovirus 71.
AB  - Human enterovirus 71 (HEV71) has emerged as a major cause of viral encephalitis
      in Southeast Asia, with increased epidemic activity observed since 1997. This is
      reflected in a large increase in scientific publications relating directly to
      HEV71. New research is elucidating details of the viral life cycle, confirming
      similarities between HEV71 and other enteroviruses. Scavenger receptor B2
      (SCARB2) is a receptor for HEV71, although other receptors are likely to be
      identified. Currently, the only strategies to prevent HEV71-associated disease
      are early diagnosis and aggressive supportive management of identified cases. As
      more information emerges regarding the molecular processes of HEV71 infection,
      further advances may lead to the development of effective antiviral treatments
      and ultimately a vaccine-protection strategy. The protective efficacies of
      several inactivated HEV71 vaccines have been confirmed in animal models,
      suggesting that an effective vaccine may become available in the next decade.

PMID- 22639072
TI  - Analysis of variability of high sensitivity C-reactive protein in lowland Ecuador
      reveals no evidence of chronic low-grade inflammation.
AB  - OBJECTIVES: C-reactive protein (CRP) is a central component of innate immune
      defenses, and high sensitivity CRP has emerged as an important biomarker of
      chronic inflammation and cardiovascular disease risk. Prior analyses of CRP
      variability have reported stable between-individual differences in CRP over time,
      but a limitation of current knowledge is that it is based on research conducted
      in post-epidemiologic transition populations. METHODS: This study evaluated CRP
      variability among adults in the southeastern region of the Ecuadorian Amazon
      where rates of infectious diseases remain high. Blood samples were collected from
      52 adults at four weekly sampling intervals and were quantified using a high
      sensitivity immunoassay. RESULTS: Median CRP concentration was 0.52 mg/l. About
      34.6% of participants had CRP >3 mg/l at one time point, but no individuals had
      CRP >3 mg/l across two or more sampling intervals, and within-individual
      correlations revealed low levels of stable, between-individual differences in
      CRP. The application of current guidelines for the assessment of chronic
      inflammation failed to detect a single case of "high risk" CRP. CONCLUSIONS: This
      study is the first to investigate CRP variability in a nonindustrialized, high
      infectious disease environment. It documents a pattern of variation over time
      that is distinct from prior research, with no evidence for chronic low-grade
      inflammation. These results may have substantial implications for research on
      inflammation and diseases of aging globally, as well as for scientific
      understandings of the regulation of inflammation.

PMID- 22639073
TI  - Breast milk fatty acid composition differs between overweight and normal weight
      women: the STEPS Study.
AB  - OBJECTIVE: We studied differences in breast milk fatty acid (FA) composition
      between overweight and normal weight women and the effect of FA composition on
      children's cholesterol concentrations at 13 months and growth from birth to 13
      months. METHODS: Samples were collected from lactating women (n = 100)
      participating in STEPS study at infant's age of 3 months, and FA composition was
      analyzed with gas chromatography. Diet of mother was studied with Index of Diet
      Quality at third trimester of pregnancy and with food frequency questionnaire on
      sampling day. The children's weights and heights were collected from hospital
      records at birth and during study visits at 13 months. RESULTS: Overweight
      women's breast milk compared to normal weight women's breast milk contained
      higher amount of saturated FAs (46.3 vs. 43.6 %, P = 0.012), lower amount of n
      3FAs (2.2 vs. 2.7 %, P = 0.010), lower ratio of unsaturated to saturated FAs (1.1
      vs. 1.3, P = 0.008), and higher ratio of n-6 to n-3 FAs (5.7 vs. 4.9, P = 0.031)
      than those of normal weight women even after adjusting for maternal diet (P <
      0.05 for all). Normal weight women adhered more to dietary recommendations during
      pregnancy, whereas no differences were found in diet at sampling 3 months
      postpartum. The children's weight gains correlated with saturated FAs (R = 0.22,
      P = 0.04) and the ratio of unsaturated to saturated FAs (R = -0.23, P = 0.038) in
      milk; however, effects diminished after adjusting for total duration of
      breastfeeding. Milk FA composition was not associated with children's cholesterol
      concentrations at 13 months. CONCLUSIONS: Breast milk FA composition differed
      between overweight and normal weight women.

PMID- 22639075
TI  - Plant growth-promoting rhizobacteria associated with ancient clones of creosote
      bush (Larrea tridentata).
AB  - Plant growth-promoting rhizobacteria (PGPR) are common components of the
      rhizosphere, but their role in adaptation of plants to extreme environments is
      not yet understood. Here, we examined rhizobacteria associated with ancient
      clones of Larrea tridentata in the Mohave desert, including the 11,700-year-old
      King Clone, which is oldest known specimen of this species. Analysis of
      unculturable and culturable bacterial community by PCR-DGGE revealed taxa that
      have previously been described on agricultural plants. These taxa included
      species of Proteobacteria, Bacteroidetes, and Firmicutes that commonly carry
      traits associated with plant growth promotion, including genes encoding
      aminocyclopropane carboxylate deaminase and beta-propeller phytase. The PGPR
      activities of three representative isolates from L. tridentata were further
      confirmed using cucumber plants to screen for plant growth promotion. This study
      provides an intriguing first view of the mutualistic bacteria that are associated
      with some of the world's oldest living plants and suggests that PGPR likely
      contribute to the adaptation of L. tridentata and other plant species to harsh
      environmental conditions in desert habitats.

PMID- 22639076
TI  - Spontaneous ultra-weak light emissions from wheat seedlings are rhythmic and
      synchronized with the time profile of the local gravimetric tide.
AB  - Semi-circadian rhythms of spontaneous photon emission from wheat seedlings
      germinated and grown in a constant environment (darkened chamber) were found to
      be synchronized with the rhythm of the local gravimetric (lunisolar) tidal
      acceleration. Time courses of the photon-count curves were also found to match
      the growth velocity profile of the seedlings. Pair-wise analyses of the data-
      growth, photon count, and tidal--by local tracking correlation always revealed
      significant coefficients (P > 0.7) for more than 80% of any of the time periods
      considered. Using fast Fourier transform, the photon-count data revealed periodic
      components similar to those of the gravimetric tide. Time courses of biophoton
      emissions would appear to be an additional, useful, and innovative tool in both
      chronobiological and biophysical studies.

PMID- 22639077
TI  - Dichrometer errors resulting from large signals or improper modulator phasing.
AB  - A single-beam spectrometer equipped with a photoelastic modulator can be
      configured to measure a number of different parameters useful in characterizing
      chemical and biochemical materials including natural and magnetic circular
      dichroism, linear dichroism, natural and magnetic fluorescence-detected circular
      dichroism, and fluorescence polarization anisotropy as well as total absorption
      and fluorescence. The derivations of the mathematical expressions used to extract
      these parameters from ultraviolet, visible, and near-infrared light-induced
      electronic signals in a dichrometer assume that the dichroic signals are
      sufficiently small that certain mathematical approximations will not introduce
      significant errors. This article quantifies errors resulting from these
      assumptions as a function of the magnitude of the dichroic signals. In the case
      of linear dichroism, improper modulator programming can result in errors greater
      than those resulting from the assumption of small signal size, whereas for
      fluorescence polarization anisotropy, improper modulator phase alone gives
      incorrect results. Modulator phase can also impact the values of total absorbance
      recorded simultaneously with linear dichroism and total fluorescence.

PMID- 22639078
TI  - Multiple ligand docking by Glide: implications for virtual second-site screening.
AB  - Performance of Glide was evaluated in a sequential multiple ligand docking
      paradigm predicting the binding modes of 129 protein-ligand complexes
      crystallized with clusters of 2-6 cooperative ligands. Three sampling protocols
      (single precision-SP, extra precision-XP, and SP without scaling ligand atom
      radii-SP hard) combined with three different scoring functions (GlideScore,
      Emodel and Glide Energy) were tested. The effects of ligand number, docking order
      and druglikeness of ligands and closeness of the binding site were investigated.
      On average 36% of all structures were reproduced with RMSDs lower than 2 A.
      Correctly docked structures reached 50% when docking druglike ligands into closed
      binding sites by the SP hard protocol. Cooperative binding to metabolic and
      transport proteins can dramatically alter pharmacokinetic parameters of drugs.
      Analyzing the cytochrome P450 subset the SP hard protocol with Emodel ranking
      reproduced two-thirds of the structures well. Multiple ligand binding is also
      exploited by the fragment linking approach in lead discovery settings. The HSP90
      subset from real life fragment optimization programs revealed that Glide is able
      to reproduce the positions of multiple bound fragments if conserved water
      molecules are considered. These case studies assess the utility of Glide in
      sequential multiple docking applications.

PMID- 22639079
TI  - Molecular simulation and docking studies of Gal1p and Gal3p proteins in the
      presence and absence of ligands ATP and galactose: implication for
      transcriptional activation of GAL genes.
AB  - The Gal4p mediated transcriptional activation of GAL genes requires the
      interaction between Gal3p bound with ATP and galactose and Gal80p. Though
      numerous studies suggest that galactose and ATP activate Gal3p/Gal1p interaction
      with Gal80p, neither the mechanism of activation nor the interacting surface that
      binds to Gal80p is well understood. In this study we investigated the dynamics of
      Gal3p and Gal1p in the presence and absence of ligands ATP and galactose to
      understand the role played by dynamics in the function of these proteins through
      molecular dynamics simulation and protein-protein docking studies. We performed
      simulations totaling to 510 ns on both Gal1p and Gal3p proteins in the presence
      and absence of ligands ATP and galactose. We find that, while binding of ligands
      ATP and galactose to Gal3p/Gal1p do not affect the global conformation of
      proteins, some local conformational changes around upper-lip helix including
      insertion domain are observed. We observed that only in the presence of ATP and
      galactose, Gal3p displays opening and closing motion between the two domains. And
      because of this motion, a binding interface, which is largely hydrophobic, opens
      up on the surface of Gal3p and this surface can bind to Gal80p. From our
      simulation studies we infer probable docking sites for Gal80p on Gal3p/Gal1p,
      which were further ascertained by the docking of Gal80p on to ligand bound Gal1p
      and Gal3p proteins, and the residues at the interface between Gal3p and Gal80p
      are identified. Our results correlate quite well with the existing body of
      literature on functional and dynamical aspects of Gal1p and Gal3p proteins.

PMID- 22639080
TI  - Understanding the molecular interactions of different radical scavengers with
      ribonucleotide reductase M2 (hRRM2) domain: opening the gates and gaining access.
AB  - We employed a combination of molecular docking and dynamics to understand the
      interaction of three different radical scavengers (SB-HSC21, ABNM13 and trimidox)
      with ribonucleotide reductase M2 (hRRM2) domain. On the basis of the observed
      results, we can propose how these ligands interact with the enzyme, and cease the
      radical transfer step from the di-iron center to TYR176. All the ligands alter
      the electron density over TYR176, -OH group by forming an extremely stable H-bond
      with either -NHOH group, or with phenolic hydroxyl group of the ligands. This
      change in electronic density disrupts the water bridge between TYR176, -OH and
      the di-iron center, which stops the single electron transfer process from TYR176,
      -OH to iron. As a consequence the enzyme is inhibited. Another interesting
      observation that we are reporting is the two stage gate keeping mechanism of the
      RR active site tunnel. We describe these as the outer Gate-1 controlled by
      ARG330, and the inner Gate-2 controlled by SER263, PHE240, and PHE236. We also
      observed a dynamic conformational shift in these residues, the incoming ligands
      can go through, and interact with the underlying TYR176, -OH group. From the
      study we found the active-site of hRRM2 is extremely flexible and shows a
      significant induced fit.

PMID- 22639081
TI  - Safety and efficacy of an E2 glycoprotein subunit vaccine produced in mammalian
      cells to prevent experimental infection with bovine viral diarrhoea virus in
      cattle.
AB  - Bovine viral diarrhea (BVD) infection caused by bovine viral diarrhea virus
      (BVDV), a Pestivirus of the Flaviviridae family, is an important cause of
      morbidity, mortality and economical losses in cattle worldwide. E2 protein is the
      major glycoprotein of BVDV envelope and the main target for neutralising
      antibodies (NAbs). Different studies on protection against BVDV infection have
      focused on E2, supporting its putative use in subunit vaccines. A truncated
      version of type 1a BVDV E2 (tE2) expressed in mammalian cells was used to
      formulate an experimental oleous monovalent vaccine. Immunogenicity was studied
      through immunisation of guinea pigs and followed by trials in cattle. Calves of 8
      12 months were vaccinated, twice with a 4 week interval, with either a tE2
      subunit vaccine (n = 8), a whole virus inactivated vaccine (n = 8) or left
      untreated as negative control group (n = 8). Four weeks after the last
      immunisation the animals were experimentally challenged intranasally with a non
      cythopathic BVDV strain. Following challenge, BVDV was isolated from all
      unvaccinated animals, while 6 out of 8 animals vaccinated with tE2 showed
      complete virological protection indicating that the tE2 vaccine presented a
      similar performance to a satisfactory whole virus inactivated vaccine.

PMID- 22639082
TI  - Solar radiation stress in climbing snails: behavioural and intrinsic features
      define the Hsp70 level in natural populations of Xeropicta derbentina
      (Pulmonata).
AB  - Ectotherms from sunny and hot environments need to cope with solar radiation.
      Mediterranean land snails of the superfamily Helicoidea feature a behavioural
      strategy to escape from solar radiation-induced excessive soil heating by
      climbing up vertical objects. The height of climbing, and also other parameters
      like shell colouration pattern, shell orientation, shell size, body mass, actual
      internal and shell surface temperature, and the interactions between those
      factors may be expected to modulate proteotoxic effects in snails exposed to
      solar radiation and, thus, their stress response. Focussing on natural
      populations of Xeropicta derbentina, we conducted a 'snapshot' field study using
      the individual Hsp70 level as a proxy for proteotoxic stress. In addition to
      correlation analyses, an IT-model selection approach based on Akaike's
      Information Criterion was applied to evaluate a set of models with respect to
      their explanatory power and to assess the relevance of each of the above
      mentioned parameters for individual stress, by model averaging and parameter
      estimation. The analysis revealed particular importance of the individuals' shell
      size, height above ground, the shell colouration pattern and the interaction
      height * orientation. Our study showed that a distinct set of behavioural traits
      and intrinsic characters define the Hsp70 level and that environmental factors
      and individual features strongly interact.

PMID- 22639083
TI  - Combating the drug resistance of cisplatin using a platinum prodrug based
      delivery system.

PMID- 22639084
TI  - Anterocollis and camptocormia in parkinsonism: a current assessment.
AB  - Postural deformities in parkinsonian syndromes are well recognized, but poorly
      understood and largely refractory to available therapies. In recent times a
      number of hypotheses have been proposed to explain the underlying etiology of
      anterocollis and camptocormia, but currently there is no consensus. As these
      conditions are more precisely characterized we begin to uncover that this is a
      heterogeneous and evolving phenomenon. These conditions bring to light the
      inadequacies of our current tools to study biomechanics of posture, neuromuscular
      disorders, and dystonic muscular contractions. The development of objective,
      accurate tools to directly study and measure the severity of these postural
      disorders will allow for further understanding of the pathophysiology, the
      development of novel therapeutics, and adequate clinical trial design.

PMID- 22639085
TI  - Adult tree swallow survival on the polychlorinated biphenyl-contaminated Hudson
      River, New York, USA, between 2006 and 2010.
AB  - The upper Hudson River basin in east central New York, USA, is highly
      contaminated, primarily with polychlorinated biphenyls (PCBs). Reduced adult
      survival has been documented in tree swallows (Tachycineta bicolor) at a
      similarly PCB-contaminated river system in western Massachusetts. The purpose of
      the present study was to assess whether adult survival of tree swallows was
      likewise affected in the Hudson River basin. Between 2006 and 2010, a total of
      521 female tree swallows were banded, of which 148 were retrapped at least once.
      The authors used Program MARK and an information theoretic approach to test the
      hypothesis that PCB contamination reduced annual survival of female tree
      swallows. The model that best described the processes that generated the capture
      history data included covariate effects of year and female plumage coloration on
      survival but not PCB/river. Annual survival rates of brown-plumaged females
      (mostly one year old) were generally lower (mean phi=0.39) than those of blue
      plumaged females (mean phi=0.50, one year or older). Poor early spring weather in
      2007 was associated with reduced survival in both plumage-color groups compared
      to later years. Models with the effects of PCB exposure on survival (all
      DeltaAICc values >5.0) received little support.

PMID- 22639086
TI  - NEIL1 binding to DNA containing 2'-fluorothymidine glycol stereoisomers and the
      effect of editing.
AB  - Thymine glycol (Tg), one of the oxidized bases formed in DNA by reactive oxygen
      species, is repaired by the DNA glycosylases such as NEIL1, NTH1 and Endo III. In
      our recent studies, we showed that NEIL1's catalytic efficiency and lesion
      specificity are regulated by an RNA-editing adenosine deamination reaction. In
      this study, we synthesized oligodeoxynucleotides containing 2'-fluorothymidine
      glycol with either ribo or arabino configuration and investigated the binding of
      these modified DNAs with the unedited and edited forms of human NEIL1 along with
      E. coli Endo III. For the two forms of hNEIL1, binding affinities to FTg
      containing DNA were similar indicating that the editing effect is more subtle
      than to simply alter substrate affinity. While the NEIL1-binding to FTg
      containing DNAs was largely insensitive to C5 and 2' stereochemistry, a
      preference was observed for the FTg-G pair over the FTg-A pair. In addition, we
      found that optimal binding is observed with Endo III and duplex DNA with
      riboFTg(5S) paired with dG. The modified DNAs reported here will provide useful
      tools for further characterizing the interaction between DNA repair glycosylases
      and thymine glycol containing DNA.

PMID- 22639087
TI  - Renal denervation in a patient with prior renal artery stenting.
AB  - This is a case report of a 69-year-old female with treatment-resistant severe
      arterial hypertension despite prior successful percutaneous intervention to both
      renal arteries for significant renal artery stenoses (stenting of the right and
      balloon angioplasty of the left renal artery). The office blood pressure was
      221/108 mm Hg at baseline. Secondary hypertension was ruled out and catheter
      based renal denervation performed (distal to the stent in the right renal artery
      and in the usual fashion in the left renal artery) without complications. The
      office blood pressure decreased at 1- and 3-month follow-up to 185/93 mm Hg and
      182/95 mm Hg, respectively. This case illustrates the feasibility and potential
      efficacy of catheter-based renal denervation in patients with a renal artery
      stent, an important finding as persistent hypertension is common in patients
      despite successful renal artery stenting and currently available trials examining
      renal denervation have excluded patients with prior renal artery stents.

PMID- 22639088
TI  - Defluorination of 4-fluorophenol by cytochrome P450(BM3)-F87G: activation by long
      chain fatty aldehydes.
AB  - Cytochrome P450(BM3)-F87G catalyzed the oxidative defluorination of 4
      fluorophenol, followed by reduction of the resulting benzoquinone to hydroquinone
      via the NADPH P450-reductase activity of the enzyme. The k (cat) and K (m) for
      this reaction were 71 +/- 5 min(-1) and 9.5 +/- 1.3 mM, respectively. Co
      incubation of the reaction mixture with long chain aldehydes stimulated the
      defluorination reaction, with the 2,3-unsaturated aldehyde, 2-decenal producing a
      12-fold increase in catalytic efficiency. At 150 MUM aldehyde, k (cat) increased
      to 158 +/- 4, while K (m) decreased to 1.8 +/- 0.2. The effects of catalase,
      glutathione and ascorbate on the reaction were all consistent with a direct
      oxygen insertion mechanism, as opposed to a radical mechanism. The study
      demonstrates the potential use of P450(BM3) mutants in oxidative defluorination
      reactions, and characterizes the novel stimulatory action of straight chain
      aldehydes on this activity.

PMID- 22639089
TI  - Extracellular expression and characterization of thermostable lipases, LIP8,
      LIP14 and LIP18, from Yarrowia lipolytica.
AB  - Two new lipases, LIP14 and LIP18, along with LIP8 from Yarrowia lipolytica MSR80
      were functionally expressed as extracellular proteins with an IgG tag using
      Escherichia coli HB101 pEZZ18 host vector system. Each enzyme had an optimal
      activity at pH 7 and 40  degrees C and was activated by 6 mM Ca(2+) and 90 %
      (v/v) non-polar solvents but inhibited by 10 mM of each 1,10-phenanthraline,
      DTNB, PMSF and N-bromosuccinamide. All the enzymes were thermostable with t(1/2)
      of 52 min, 49 min and 68 min for LIP8, LIP14 and LIP18 at 80  degrees C,
      respectively. LIP18 was most thermostable among all with a high arginine: lysine
      ratio and proline content. All the three lipases showed a preference for oleic
      acid rich triacylglycerols and oils.

PMID- 22639090
TI  - Regioselective synthesis of 1,3,5-adamantanetriol from 1,3-adamantanediol using
      Kitasatospora cells.
AB  - Washed cells (62 mg) of Kitasatospora sp. GF12 in 4 ml buffer (pH 7) catalyzed
      the regioselective hydroxylation of 60 mM 1,3-adamantanediol [1,3-ad(OH)(2)] to
      30.9 mM 1,3,5-adamantanetriol [1,3,5-ad(OH)(3)] over 120 h at 24  degrees C.
      Glycerol at 400 mM was added to the reaction mixture to recycle the intracellular
      NADH/NADPH. Whole cells of GF12, also catalyzed the hydroxylation of 10 mM 1
      adamantanol (1-adOH), to 3.6 mM 1,3,5-ad(OH)(3).

PMID- 22639091
TI  - Real-time quantitative analysis of the influence of blue light on citrinin
      biosynthetic gene cluster expression in Monascus.
AB  - When Monascus MX was grown under blue light instead of in the dark, citrinin
      production increased from 478 mg l(-1) to 698 mg l(-1). To explain this, the
      expression of the pksCT gene, which encodes citrinin polyketide synthase, and of
      5 ORFs around it, were monitored. Blue light enhanced citrinin production by
      upregulating the expression of orf1, orf3, and orf4, indicating that pksCT was
      not the key gene responsible for the quantity of citrinin production in blue
      light.

PMID- 22639092
TI  - Enhanced accumulation of secondary metabolites in hairy root cultures of
      Scutellaria lateriflora following elicitation.
AB  - Hairy root cultures of Scutellaria lateriflora were established using
      Agrobacterium rhizogenes A4 and produced acteoside (18.5 mg g(-1) dry wt),
      baicalin (14.5 mg g(-1) dry wt) and wogonoside (12 mg g(-1) dry wt). Yeast
      extract (50 MUg ml(-1)) increased acteoside production 1.4-fold and flavone
      production 1.7-fold after 7 and 14 days of elicitation. Addition of
      Pectobacterium carotovorum lysate in the stationary phase of the hairy root
      culture stimulated only the accumulation of wogonin to 30 mg g(-1) dry wt. The
      production of wogonin in hairy roots could be associated with its role as a
      phytolaexin.

PMID- 22639093
TI  - Response of osteoclasts to titanium surfaces with increasing surface roughness:
      an in vitro study.
AB  - Osteoclasts are responsible for bone resorption and implant surface roughness
      promotes osseointegration. However, little is known about the effect of roughness
      on osteoclast activity. This study aims at the characterization of osteoclastic
      response to surface roughness. The number of osteoclasts, the tartrate-resistant
      acid phosphatase and matrix metalloproteinase (MMP) activities, the cell
      morphology and the actin-ring formation were examined on smooth (TS), acid-etched
      (TA) and sandblasted acid-etched (TLA) titanium and on native bone. Cell
      morphology was comparable on TA, TLA and bone, actin rings being similar in size
      on TLA and bone, but smaller on TA and virtually absent on TS. Gelatin zymography
      revealed increased proMMP-9 expression on TA, TLA, and bone compared to TS. In
      general, osteoclasts show similar characteristics on rough titanium surfaces and
      on bone, but reduced activity on smooth titanium surfaces. These results offer
      some insight into the involvement of osteoclasts in remodeling processes around
      implant surfaces.

PMID- 22639094
TI  - XRCC1 Arg194Trp polymorphism, risk of nonmelanoma skin cancer and extramammary
      Paget's disease in a Japanese population.
AB  - The X-ray repair cross-complementing groups 1 gene plays an important role in
      base excision repair. At least three common single nucleotide polymorphisms
      frequently occur in this gene (Arg399Gln, Arg194Trp and Arg280His). Recent
      studies reported that these polymorphisms were associated with not only risk of
      visceral malignancy but also that of skin cancer such as basal cell carcinoma and
      squamous cell carcinoma, whereas the results of previous study vary among races.
      In this case-control study, we investigated whether these single nucleotide
      polymorphisms were associated with the risk of skin cancer in a Japanese
      population. The study population was composed of 197 patients with skin cancer
      (27 actinic keratoses, 47 basal cell carcinomas, 27 squamous cell carcinomas, 29
      Bowen's diseases, 46 malignant melanomas and 21 extramammary Paget's diseases)
      and 93 control subjects. We genotyped two single nucleotide polymorphisms
      (Arg194Trp and Arg399Gln) using polymerase chain reaction-restriction fragments
      length polymorphism analysis. We found a significantly increased risk for basal
      cell carcinoma, squamous cell carcinoma and extramammary Paget's disease
      associated with Arg194Trp [adjusted odds ratio (AOR) = 2.347, 3.587, 3.741, 95 %
      confidence interval (CI) 1.02-5.39, 1.19-10.8, 1.15-12.2, respectively]. We also
      found a significantly decreased risk for basal cell carcinoma associated with
      Gln399Gln (AOR = 0.259, 95 % CI 0.07-0.96). Our data suggest that the Arg194Trp
      polymorphism could be associated with nonmelanoma skin cancer and extramammary
      Paget's disease risk in a Japanese population.

PMID- 22639095
TI  - Abrogating effect of a xanthophyll carotenoid astaxanthin on the stem cell factor
      induced stimulation of human epidermal pigmentation.
AB  - We established a model for the stem cell factor (SCF)-associated stimulation of
      human epidermal equivalent (HEE) pigmentation. The addition of SCF (at 5 nM)
      gradually stimulated the visible pigmentation of HEEs over 14 days of treatment.
      A time course study using real-time RT-PCR and western blotting analysis
      demonstrated that the expression of all melanocyte-specific genes and proteins
      examined was gradually up-regulated over 7-10 days of treatment with SCF. The
      addition of astaxanthin (Ax) at concentrations of 1, 4, or 8 MUM markedly
      abolished the SCF- but not the endothelin (EDN)1-elicited increase in visible
      pigmentation over 14 days in a dose-dependent manner, with almost complete
      inhibition at 8 MUM. While no degeneration of the epidermal tissue was visible at
      day 14 by HE staining, melanin deposition throughout the epidermis was markedly
      reduced in the Ax-treated HEEs at day 14 compared to untreated controls. Ax
      significantly reduced the eumelanin content of HEEs to the non-SCF-stimulated
      level at concentrations of 4 or 8 MUM compared with untreated controls. Real-time
      RT-PCR and western blotting of Ax-treated HEEs revealed that the SCF-stimulated
      expression of tyrosinase (TYR), TYR-related protein-1 (TYRP1), and Pmel17, as
      well as microphthalmia-associated transcription factor (MITF), is significantly
      suppressed by Ax at the transcriptional and translational levels. Studies using
      cultured normal human melanocytes revealed that pre-treatment with Ax interrupts
      the SCF- but not the EDN1-induced stimulation of TYR activity, and there was no
      direct inhibitory effect of Ax on TYR activity in vitro. These findings indicate
      that Ax attenuates SCF-stimulated pigmentation by directly interrupting SCF
      associated intracellular signaling linkages through increased expression of MITF,
      which leads to the stimulated expression of melanogenic genes and proteins in a
      reactive oxygen species depletion-independent mechanism.

PMID- 22639096
TI  - Effect of triazine derivative added to denture materials on a microcosm biofilm
      model.
AB  - The aim of this study was to assess the effect of triazine incorporation to
      denture materials on biofilm formation of saliva derived from microcosms of
      patients who are positive for Candida albicans. Biofilms were formed on microwave
      cured acrylic resin, one hard denture liner, and two soft denture liners
      containing 0, 2.5, 5, and 10% triazine. For experimental subset (n = 10),
      mechanical properties of the materials and colony-forming unit counts from the
      biofilms formed on the materials were assessed. Flexural strength and modulus
      decreased with the addition of 2.5% triazine (p < 0.01). In general, the addition
      of 5 and 10% triazine leaded to more soluble materials (p < 0.001). Saliva donor
      with candidiasis resulted in higher counts of total microorganisms (p = 0.0294)
      and Streptococci (p = 0.0008). Soft denture liners showed the highest counts for
      total microorganisms, Streptococci, and Candida species (p < 0.001). The addition
      of triazine directly to denture materials was not beneficial in reducing biofilm
      formation in a complex biofilm model.

PMID- 22639098
TI  - [Erich von Baeyer: the turbulent life of an outstanding German-American
      radiologist].

PMID- 22639097
TI  - Correlation between instrumental activities of daily living and white matter
      hyperintensities in amnestic mild cognitive impairment: results of a cross
      sectional study.
AB  - Although some studies have supported the association between white matter
      hyperintensities (WMH) and cognitive impairment, whether WMH are associated with
      the impairments in instrumental activities of daily living (IADLs) remains
      unknown. This cross-sectional study investigated differences in basic ADLs and
      IADLs among different severity of WMH in a large, well-defined registry of
      patients with amnestic mild cognitive impairment (aMCI). 1,514 patients with aMCI
      were divided into three groups according to the degree of WMH (1,026 mild, 393
      moderate, and 95 severe). We compared the total IADL scores and analyzed the
      prevalence of the impairment for each IADL item for each group. The severity of
      WMH was associated with the impairments in IADLs. Among 15 Seoul IADL items,
      "using public transportation", "going out (short distance)", "grooming" and
      "participating in leisure activities/hobbies" showed greater positive association
      with the severity of WMH. WMH in patients with aMCI were associated with the
      impairments in IADLs but not in basic ADLs. These findings are likely to be more
      obvious with respect to using public transportation, going out (short distances),
      shopping, grooming and participating in leisure activities/hobbies.

PMID- 22639099
TI  - Informal and formal support among community-dwelling Japanese American elders
      living alone in Chicagoland: an in-depth qualitative study.
AB  - A key public health approach to promote independent living and avoid nursing home
      placement is ensuring that elders can obtain adequate informal support from
      family and friends, as well as formal support from community services. This study
      aims to describe the use of informal and formal support among community-dwelling
      Nikkei elders living alone, and explore perceived barriers hindering their use of
      such support. We conducted English and Japanese semi-structured, open-ended
      interviews in Chicagoland with a convenience sample of 34 Nikkei elders age 60+
      who were functionally independent and living alone; 9 family/friends; and 10
      local service providers. According to participants, for informal support, Nikkei
      elders relied mainly on: family for homemaking and health management; partners
      for emotional and emergency support; friends for emotional and transportation
      support; and neighbors for emergency assistance. Perceived barriers to informal
      support included elders' attitudinal impediments (feeling burdensome,
      reciprocating support, self-reliance), family-related interpersonal circumstances
      (poor communication, distance, intergenerational differences); and
      friendship/neighbor-related interpersonal situations (difficulty making friends,
      relocation, health decline/death). For formal support, Nikkei elders primarily
      used adult day care/cultural programs for socializing and learning and in-home
      care for personal/homemaking assistance and companionship. Barriers to formal
      support included attitudinal impediments (stoicism, privacy, frugality);
      perception of care (incompatibility with services, poor opinions of in-home care
      quality); and accessibility (geographical distance, lack of transportation). In
      summary, this study provides important preliminary insights for future community
      strategies that will target resources and training for support networks of Nikkei
      elders living alone to maximize their likelihood to age in place independently.

PMID- 22639101
TI  - Chitosan-based heterogeneous catalysts for enantioselective Michael reaction.
AB  - Novel chitosan-supported cinchona alkaloids have been developed as heterogeneous
      catalysts for enantioselective Michael reaction. As-synthesized products as
      organocatalysts for asymmetric Michael reaction have a high efficiency, providing
      highly functionalized products (containing adjacent quaternary and tertiary
      stereocenters) with good stereoselectivity (up to 93% enantiomeric excess) in
      high yields and recyclability (up to five runs).

PMID- 22639100
TI  - Validation of macromolecular flexibility in solution by small-angle X-ray
      scattering (SAXS).
AB  - The dynamics of macromolecular conformations are critical to the action of
      cellular networks. Solution X-ray scattering studies, in combination with
      macromolecular X-ray crystallography (MX) and nuclear magnetic resonance (NMR),
      strive to determine complete and accurate states of macromolecules, providing
      novel insights describing allosteric mechanisms, supramolecular complexes, and
      dynamic molecular machines. This review addresses theoretical and practical
      concepts, concerns, and considerations for using these techniques in conjunction
      with computational methods to productively combine solution-scattering data with
      high-resolution structures. I discuss the principal means of direct
      identification of macromolecular flexibility from SAXS data followed by critical
      concerns about the methods used to calculate theoretical SAXS profiles from high
      resolution structures. The SAXS profile is a direct interrogation of the
      thermodynamic ensemble and techniques such as, for example, minimal ensemble
      search (MES), enhance interpretation of SAXS experiments by describing the SAXS
      profiles as population-weighted thermodynamic ensembles. I discuss recent
      developments in computational techniques used for conformational sampling, and
      how these techniques provide a basis for assessing the level of the flexibility
      within a sample. Although these approaches sacrifice atomic detail, the knowledge
      gained from ensemble analysis is often appropriate for developing hypotheses and
      guiding biochemical experiments. Examples of the use of SAXS and combined
      approaches with X-ray crystallography, NMR, and computational methods to
      characterize dynamic assemblies are presented.

PMID- 22639102
TI  - Sequence comparison of three infectious molecular clones of RD-114 virus.
AB  - RD-114 virus is a replication-competent feline endogenous retrovirus. RD-114
      virus contaminates several feline and canine live attenuated vaccines and the
      issue of contamination of RD-114 virus in vaccines should be solved. To date,
      three infectious molecular clones (pSc3c, pCRT1, and pRD-UCL) have been reported.
      In this study, we sequenced the entire nucleotide sequence of pRD-UCL and
      compared the nucleotide sequences of the three infectious molecular clones. As a
      result, these three infectious clones were nearly identical with each other in
      gag-pol and env coding regions. These data support the notion that the active
      locus of infectious RD-114 virus is single in the feline genome. The length of
      long terminal repeat (LTR) of pCRT1 was 47 bp shorter than those of pSc3c and pRD
      UCL. The 47-bp sequence named direct repeat A (DR-A) was duplicated in the U3
      region in pSc3c and pRD-UCL. Although several potential enhancer binding sites
      are present in the DR-A, there was no significant difference in promoter
      activities between the LTRs of pRD-UCL and pCRT1 in two human cell lines. We also
      analyzed the splicing pattern of the RD-114 virus by reverse transcription
      polymerase chain reaction and confirmed that RD-114 virus is a simple retrovirus.
      The data presented here will provide basic information about RD-114 virus to
      solve the contamination issue in live attenuated vaccines.

PMID- 22639103
TI  - Serological prevalence, genetic identification, and characterization of the first
      strains of avian hepatitis E virus from chickens in Korea.
AB  - Avian hepatitis E virus (avian HEV) is associated with hepatitis-splenomegaly
      (HS) syndrome or big liver and spleen disease in chickens. At least three
      genotypes of avian HEV have been identified from chickens worldwide. A total of
      297 serum samples collected from chickens in 35 flocks in Korea were tested for
      avian HEV antibody with an enzyme-linked immunosorbent assay. The results showed
      that approximately 57 % of chicken flocks and 28 % of chickens from Korea were
      positive for antibodies to avian HEV. Thirteen pooled fecal samples from chickens
      were tested for avian HEV RNA by RT-PCR, and three fecal samples were positive.
      The partial helicase and capsid genes of the Korean avian HEV isolates were
      determined, and sequence analyses revealed that the Korean avian HEV isolates
      were clustered together and closely related to the genotype 1 avian HEV from
      Australia. The complete genomic sequence of a Korean avian HEV strain HH-F9 from
      a broiler breeder was determined, and shown to be 6,653 nt in length, excluding
      the poly (A) tail, which is 1 nt shorter than the prototype avian HEV from
      chicken with HS syndrome in the United States. Compared to the full-length
      sequences of other 5 known avian HEV strains worldwide, the Korean avian HEV
      shared approximately 83-97 % nucleotide sequence identity. The finding that
      Korean avian HEV belongs to genotype 1 avian HEV which was previously identified
      only from chickens in Australia has significant implication in understanding the
      global epidemiology of avian HEV.

PMID- 22639104
TI  - Molecular epidemiology of infectious bursal disease viruses isolated from
      Southern China during the years 2000-2010.
AB  - We performed a molecular epidemiology study of infectious bursal disease virus
      (IBDV) from six provinces in southern China by analyzing IBDVs isolated during
      the years 2000-2010. Sequence analysis of hypervariable regions of the VP2 gene
      (vVP2) in the genome of these isolates revealed that the majority of these
      viruses (45/59) were characterized as vv (very virulent) IBDV genotype, 12 out of
      59 isolates were avirulent IBDV genotype and two from Guangxi were intermediate
      IBDV genotype. Phylogenetic analysis revealed that 45 vvIBDV genotype isolates
      have divided into five groups, all displaying strong divergence from the
      currently used vaccine strains. In all isolates, 14 non-critical amino acid
      substitutions were found in vVP2. The isolates from 2006 to 2010 had more
      substitutions (11 sites) than the isolates from 2000 to 2005 (7 sites). This
      study demonstrates that there were different genotypes of IBDV prevailing in six
      provinces of southern China. The mutations in vVP2 were common, which might be
      one of the reasons for the evolution of the IBDVs. Therefore, in regards to IBDV
      prevention, it is vital to have continuous monitoring of the genetic variability
      (long-term tracking of viral evolution) to provide optimal protection against
      IBDV.

PMID- 22639105
TI  - Mercury in litterfall and upper soil horizons in forested ecosystems in Vermont,
      USA.
AB  - Mercury (Hg) is an atmospheric pollutant that, in forest ecosystems, accumulates
      in foliage and upper soil horizons. The authors measured soil and litterfall Hg
      at 15 forest sites (northern hardwood to mixed hardwood/conifer) throughout
      Vermont, USA, to examine variation among tree species, forest type, and soils.
      Differences were found among the 12 tree species sampled from at least two sites,
      with Acer pensylvanicum having significantly greater litterfall total Hg
      concentration. Senescent leaves had greater Hg concentrations if they originated
      lower in the canopy or had higher surface:weight ratios. Annual litterfall Hg
      flux had a wide range, 12.6 to 28.5 ug/m(2) (mean, 17.9 ug/m(2) ), not related to
      forest type. Soil and Hg pools in the Oi horizon (litter layer) were not related
      to the measured Hg deposition flux in litterfall or to total modeled Hg
      deposition. Despite having lower Hg concentrations, upper mineral soil (A
      horizons) had greater Hg pools than organic soil horizons (forest floor) due to
      greater bulk density. Significant differences were found in Hg concentration and
      Hg/C ratio among soil horizons but not among forest types. Overall, our findings
      highlight the importance of site history and the benefits of collecting
      litterfall and soils simultaneously. Observed differences in forest floor Hg
      pools were strongly correlated with carbon pools, which appeared to be a function
      of historic land-use patterns.

PMID- 22639106
TI  - NK/T-cell lymphomas: pathobiology, prognosis and treatment paradigm.
AB  - The current World Health Organization (WHO) classification includes two types of
      natural killer (NK)-cell lymphomas: extranodal NK/T-cell lymphoma, nasal type
      (ENKL), and aggressive NK-cell leukemia (ANKL). These diseases are mostly endemic
      to East Asia and Latin America. The Epstein-Barr virus (EBV) is usually detected
      in tumor cells, suggesting that EBV plays an important role in lymphomagenesis.
      At the site of origin, ENKL can be divided into two major subtypes: nasal and
      extranasal diseases. The advanced disease presentation, highly aggressive
      clinical course, and poor prognosis of the latter are analogous to ANKL. It is
      well known that P-glycoprotein, which is a product of the multi-drug resistance
      (MDR1) gene, is expressed on neoplastic cells of ENKL or ANKL. This is a major
      cause of the refractoriness of malignant lymphoma to conventional
      chemotherapeutic regimens containing anthracycline. Recent studies, however, have
      identified that L-asparaginase-containing regimens, such as SMILE (steroid,
      methotrexate, ifosfamide, L-asparaginase and etoposide), are effective for ENKL.
      Considering the myelotoxicity of SMILE, its use in the treatment of ANKL needs
      some modifications, but this treatment scheme is promising in improving the
      prognosis of NK-cell lymphomas.

PMID- 22639107
TI  - Thymic neoplasms: a clinical update.
AB  - Thymoma is a unique neoplasm of the anterior mediastinum that is frequently
      associated with indolent growth and a variety of paraneoplastic syndromes. One
      third of cases are detected during the evaluation of myasthenia gravis.
      Classification systems of thymoma have limited ability in accurately predicting
      prognosis and course of disease. Thus, staging is the only way to predict
      clinical behavior. Encapsulated tumors that are surgically resected carry the
      best prognosis. Adjuvant radiotherapy is recommended for incompletely excised and
      most invasive thymomas. Chemotherapy in anthracycline-based chemotherapy remains
      the most effective chemotherapy for neoadjuvant, adjuvant or palliative
      treatment.

PMID- 22639108
TI  - Diagnosis of acute leukemia in cerebrospinal fluid (CSF-acute leukemia).
AB  - Cerebrospinal fluid-acute leukemia (CSF-acute leukemia) is a frequent and serious
      complication in patients with acute leukemia. One of the major problems of this
      complication is the diagnosis process itself. CSF cytology is currently
      considered the gold standard for establishing the diagnosis, a technique which
      presents various processing limitations, seriously impacting the predictive
      values. In the last 11 years, studies of CSF flow cytometry analysis done in
      patients with acute leukemia have demonstrated superiority in comparison with CSF
      cytology. Although comparative studies between these two techniques have been
      reported since 2001, no new consensus or formal changes to the gold standard have
      been established for the CSF acute leukemia diagnosis. The evidence suggests that
      positive flow cytometry cases, considered as indeterminate cases, will behave
      like disease in the central nervous system (CNS). Nevertheless, we think there
      are some variables and considerations that must be first evaluated under research
      protocols before CNS relapse can be established with only one positive flow
      cytometry analysis in the setting of indeterminate CSF samples. This paper
      proposes a diagnostic algorithm and complementary strategies.

PMID- 22639109
TI  - Local redox-cycling-based electrochemical chip device with deep microwells for
      evaluation of embryoid bodies.

PMID- 22639110
TI  - Bioconjugation of green fluorescent protein via an unexpectedly stable cyclic
      sulfonium intermediate.
AB  - Smooth converter: Bioconjugation of superfolder GFP involving the formation of an
      unusually stable, and unprecedented, cyclic sulfonium species is described. This
      sulfonium can undergo smooth reaction with a range of nucleophiles to give sulfur
      , selenium- and azide-modified GFP derivatives in high conversions.

PMID- 22639111
TI  - Population pharmacokinetics and pharmacodynamics of ribavirin in patients with
      chronic hepatitis C genotype 1 infection.
AB  - We report a population pharmacokinetic (PK) and pharmacodynamic (PD) model of
      orally administered ribavirin in patients with chronic hepatitis C virus (HCV)
      infection enrolled in a multicenter clinical trial, including the estimation of
      covariate effects on ribavirin PK parameters and sustained viral response (SVR).
      Ribavirin concentrations obtained from 144 patients, consisting of n = 71 African
      American (AA) and n = 73 Caucasian Americans (CA), during 24 weeks of therapy
      were best described by a two-compartment model with first-order absorption and
      elimination parameterized in terms of apparent oral clearance (CL/F), apparent
      central volume (Vc/F), apparent peripheral volume (Vp/F), and apparent
      intercompartmental clearance (Q/F). The typical population parameters were CL/F
      (19.0 L/h), Vc/F (1,130 L), Vp/F (4,020 L), and Q/F (38.6). The Vp/F was
      approximately 50% greater in AA compared to CA. Significant covariates in the SVR
      model included IL-28B genotype, homeostasis model assessment of insulin
      resistance, and ribavirin exposure during the first week (AUC(0-7)). The
      population PK and logistic regression models both described the observed
      ribavirin concentration data and SVR data well. These findings suggest that
      optimization of ribavirin plasma concentrations during the first week of
      ribavirin dosing is most critical in AA patients in order to increase the rate of
      SVR, especially those with the IL-28B TT genotype.

PMID- 22639112
TI  - A pilot study of a culturally targeted video intervention to increase
      participation of African American patients in cancer clinical trials.
AB  - PURPOSE: Barriers to clinical trial participation among African American cancer
      patients are well characterized in the literature. Attitudinal barriers
      encompassing fear, distrust, and concerns about ethical misconduct are also well
      documented. To increase trial accrual, these attitudes must be adequately
      addressed, yet there remains a lack of targeted interventions toward this end. We
      developed a 15-minute culturally targeted video designed to impact six specific
      attitudes of African American cancer patients toward therapeutic trials. We
      conducted a pilot study to test in the first such intervention to increase
      intention to enroll. PATIENTS AND METHODS: The primary study outcome was self
      reported likelihood to participate in a therapeutic trial. Using a mixed methods
      approach, we developed the Attitudes and Intention to Enroll in Therapeutic
      Clinical Trials (AIET) instrument, a 30-item questionnaire measuring six
      attitudinal barriers to African American trial participation. We enrolled 108
      eligible active treatment patients at a large urban cancer institute. McNemar's
      test for matched pairs was used to assess changes in attitudes and likelihood to
      enroll in a clinical trial at baseline and immediately after the video. Pre- and
      post-video AIET summative scores were analyzed by paired t-test for each
      attitudinal barrier. RESULTS: Patients' likelihood of enrolling in a clinical
      trial significantly increased post-video with 36% of the sample showing positive
      changes in intention [McNemar's chi(2) = 33.39, p < .001]. Paired t-tests showed
      significant changes in all six attitudinal barriers measured via AIET summative
      scores from pre- to post-video. CONCLUSION: These data suggest utility of our
      video for increasing African American participation in clinical trials.

PMID- 22639114
TI  - Expert opinion: future frontiers and challenges in cancer medicine.

PMID- 22639115
TI  - Cloning and sequence analysis of the heat-stable acrylamidase from a newly
      isolated thermophilic bacterium, Geobacillus thermoglucosidasius AUT-01.
AB  - A thermophilic bacterium capable of degrading acrylamide, AUT-01, was isolated
      from soil collected from a hot spring area in Montana, USA. The thermophilic
      strain grew with 0.2 % glucose as the sole carbon source and 1.4 mM acrylamide as
      the sole nitrogen source. The isolate AUT-01 was identified as Geobacillus
      thermoglucosidasius based on 16S rDNA sequence. An enzyme from the strain capable
      of transforming acrylamide to acrylic acid was purified by a series of
      chromatographic columns. The molecular weight of the enzyme was estimated to be
      38 kDa by SDS-PAGE. The enzyme activity had pH and temperature optima of 6.2 and
      70 oC, respectively. The influence of different metals and amino acids on the
      ability of the purified protein to transform acrylamide to acrylic acid was
      evaluated. The gene from G. thermoglucosidasius encoding the acrylamidase was
      cloned, sequenced, and compared to aliphatic amidases from other bacterial
      strains. The G. thermoglucosidasius gene, amiE, encoded a 38 kDa, monomeric, heat
      stable amidase that catalysed the cleavage of carbon-nitrogen bonds in
      acrylamide. Comparison of the amino acid sequence to other bacterial amidases
      revealed 99 and 82 % similarity to the amino acid sequences of Bacillus
      stearothermophilus and Pseudomonas aeruginosa, respectively.

PMID- 22639116
TI  - Sphingosine kinase 1 in viral infections.
AB  - Sphingosine kinase 1 (SphK1) is an enzyme that phosphorylates the lipid
      sphingosine to generate sphingosine-1-phosphate (S1P). S1P can act
      intracellularly as a signaling molecule and extracellularly as a receptor ligand.
      The SphK1/S1P axis has well-described roles in cell signaling, the cell
      death/survival decision, the production of a pro-inflammatory response,
      immunomodulation, and control of vascular integrity. Agents targeting the
      SphK1/S1P axis are being actively developed as therapeutics for cancer and
      immunological and inflammatory disorders. Control of cell death/survival and pro
      inflammatory immune responses is central to the pathology of infectious disease,
      and we can capitalize on the knowledge provided by investigations of SphK1/S1P in
      cancer and immunology to assess its application to selected human infections. We
      have herein reviewed the growing literature relating viral infections to changes
      in SphK1 and S1P. SphK1 activity is reportedly increased following human
      cytomegalovirus and respiratory syncytial virus infections, and elevated SphK1
      enhances influenza virus infection. In contrast, SphK1 activity is reduced in
      bovine viral diarrhea virus and dengue virus infections. Sphingosine analogs that
      modulate S1P receptors have proven useful in animal models in alleviating
      influenza virus infection but have shown no benefit in simian human
      immunodeficiency virus and lymphocytic choriomeningitis virus infections. We have
      rationalized a role for SphK1/S1P in dengue virus, chikungunya virus, and Ross
      River virus infections, on the basis of the biology and the pathology of these
      diseases. The increasing number of effective SphK1 and S1P modulating agents
      currently in development makes it timely to investigate these roles with the
      potential for developing modulators of SphK1 and S1P for novel anti-viral
      therapies.

PMID- 22639118
TI  - A temperature-limited assessment of the risk of Rift Valley fever transmission
      and establishment in the continental United States of America.
AB  - The rapid spread of West Nile virus across North America after its introduction
      in 1999 highlights the potential for foreign arboviruses to become established in
      the United States of America. Of particular concern is Rift Valley fever virus
      (RVFV), which has been responsible for multiple African epidemics resulting in
      death of both humans and livestock, as well as major economic disruption due to
      livestock loss and trade restrictions. Modern globalization, travel, and commerce
      allow viruses to easily jump from one continent to another; and it is likely only
      a matter of time before RVFV reaches North American shores. We used a degree-day
      model in combination with livestock population data and a pathways analysis to
      identify regions and times where RVFV is most likely to enter and become
      established in the United States of America. Transmission risk of the disease
      varies across the country from 325 annual risk days in parts of Florida to zero
      risk days in the far North and in high mountain regions. Areas of particular
      concern are where there are a high number of possible tranmission days, a large
      livestock population, and proximity to likely locations for the disease to enter
      the country via mosquito vector or human host. These areas should be monitored
      closely during transmission "risk seasons" so that if the virus does enter the
      country and begins to become established, it can be quickly controlled and
      eliminated before spreading further. Areas most at risk include the Baltimore and
      New York City metro areas as well as much of the region between these urban
      centers; most of Texas, especially around Houston; Florida; Atlanta; southwest
      Nebraska; southern California and Arizona; and the central valley of California.

PMID- 22639117
TI  - First experience with the new GORE Septal Occluder for the closure of multiple
      atrial septal defects.
AB  - Transcatheter closure of an atrial septal defect (ASD) is considered the standard
      of care for most of the patients with secundum ASD. The existence of multiple or
      fenestrated ASD may constitute a challenge to achieve a satisfactory result. Data
      on the usage of multiple devices for closing multiple defects are limited. The
      GORE Septal Occluder (GSO) represents a new generation of transcatheter ASD
      occluders with a design that provides superior conformability, apposition, and
      closure performance compared with the previous GORE HELEX device. The present
      case report describes the first clinical experience with the implantation of two
      GSO devices in a patient with multiple ASDs and fenestrated septum.

PMID- 22639119
TI  - Assessing the risk for dengue fever based on socioeconomic and environmental
      variables in a geographical information system environment.
AB  - An important option in preventing the spread of dengue fever (DF) is to control
      and monitor its vector (Aedes aegypti) as well as to locate and destroy suitable
      mosquito breeding environments. The aim of the present study was to use a
      combination of environmental and socioeconomic variables to model areas at risk
      of DF. These variables include clinically confirmed DF cases, mosquito counts,
      population density in inhabited areas, total populations per district, water
      access, neighbourhood quality and the spatio-temporal risk of DF based on the
      average, weekly frequency of DF incidence. Out of 111 districts investigated, 17
      (15%), covering a total area of 121 km2, were identified as of high risk, 25
      (22%), covering 133 km2, were identified as of medium risk, 18 (16%), covering
      180 km2, were identified as of low risk and 51 (46%), covering 726 km2, were
      identified as of very low risk. The resultant model shows that most areas at risk
      of DF were concentrated in the central part of Jeddah county, Saudi Arabia. The
      methods used can be implemented as routine procedures for control and prevention.
      A concerted intervention in the medium- and high-risk level districts identified
      in this study could be highly effective in reducing transmission of DF in the
      area as a whole.

PMID- 22639120
TI  - Localization of kala-azar in the endemic region of Bihar, India based on land
      use/land cover assessment at different scales.
AB  - Land cover, a critical variable in the epidemiology of kala-azar, can be remotely
      characterized by customizing and integrating "state-of-the-art" imagery at
      different spatial scales from different sensors onboard satellites. A study was
      conducted at four levels (national, state, district and village) investigating
      the role of land use/land cover (LULC) for leishmaniasis transmission resulting
      in a framework highlighting the links between LULC and areas endemic for the
      disease. Distribution maps were analysed by a probabilistic approach (Bayesian
      classifier) which produced a set of "suitability estimates" based on the
      probability of sand fly presence. The development of a sound knowledge of each
      link in the predicted sequence of satellite views offering an extraordinary
      opportunity to support the mapping of kala-azar endemicity and stratification of
      areas suitable for sand fly habitats across the country as well as at the local
      scale.

PMID- 22639121
TI  - A real-time platform for monitoring schistosomiasis transmission supported by
      Google Earth and a web-based geographical information system.
AB  - A basic framework for the rapid assessment of the risk for schistosomiasis was
      developed by combining spatial data from Google Earth(r) with a geographical
      information system (GIS) package, bundling the modules together with an Internet
      connection into a WebGIS platform. It operates through functions such as
      "search", "evaluation", "risk analysis" and "prediction" and is primarily aimed
      to be a dynamic, early-warning system (EWS) providing user-friendly, evidence
      based, near real-time awareness of the status of an important endemic disease. It
      contributes to rapid information-sharing at all levels of decision-making,
      facilitating "point-of-care" response, i.e. treatment provided at newly
      discovered transmission sites. The experience using the platform is encouraging
      and it has the potential to improve support systems and strengthen
      schistosomiasis control activities, in particular with regard to surveillance and
      EWS. It can quickly and intuitively locate early, high-risk areas, retrieve all
      important data needed as well as provide detailed, up-to-date information on the
      performance of the control programme. This WebGIS, the first of its kind in the
      People's Republic of China, is not only applicable for schistosomiasis but can
      easily be adapted for improving control of any endemic disease in any
      geographical area.

PMID- 22639122
TI  - Spatial comparison of areas at risk for schistosomiasis in the hilly and
      mountainous regions in the People's Republic of China: evaluation of the long
      term effect of the 10-year World Bank Loan Project.
AB  - The long-term effectiveness of the mainly chemotherapy-based control strategy of
      the World Bank Loan Project (WBLP) for schistosomiasis control in Chinese hilly
      and mountainous regions was evaluated with a view to determine the best road
      forward. Based on the national database of schistosomiasis prevalence for the
      periods of 1999-2001 and 2007-2008 in the People's Republic of China, a Bayesian
      regression model was used for spatial comparison of schistosomiasis risk
      distribution between two periods taking account of all the potential risk factors
      simultaneously through two latent components of random effects: spatially
      correlated heterogeneities (CH) and spatially uncorrelated heterogeneities (UH).
      Four different types of endemic areas were investigated: those that remained
      endemic despite control efforts (17 or 37.8%), those that became non-endemic (9
      or 20.0%), those that reverted back to endemicity (7 or 15.6%), and those with
      fluctuating endemicity (12 or 26.7%). The overall prevalence of schistosomiasis
      was lower in 2007-2008 compared with that in 1999-2001, but the spatial
      distribution of risk remained similar. Compared to 1999-2001, the magnitude and
      range of risk even tended to be greater in 2007-2008. UH showed a fluctuating
      pattern, while CH increased gradually doubling over the two periods. There was no
      evidence for long-term effectiveness of the WBLP chemotherapy-based control
      strategy in this region. Controlling the effect of UH is still the main aspect of
      current schistosomiasis control strategy for the hilly and mountainous regions,
      but innovative methods are urgently needed for effectively controlling UH.

PMID- 22639123
TI  - Successful outcome of an integrated strategy for the reduction of schistosomiasis
      transmission in an endemically complex area.
AB  - Schistosomiasis is one of the major public health problems in the People's
      Republic of China (and elsewhere), seriously threatening health as well as social
      and economic development. An integrated control strategy, emphasising
      transmission control but also aimed at reducing greenhouse gases, was carried out
      in Jiangling county, Hubei province from 2007 to 2009. Three villages were chosen
      for a pilot study involving removal of cattle from neighbouring, snail-infested
      grasslands, improving sanitation and construction of units for household biogas
      production in addition to routine control measures. Both prevalence and intensity
      of infection in the snails in the neighbourhood were greatly reduced after two
      years of implementation, while the prevalence of schistosomiasis in humans in the
      three villages had been reduced by 29%, 34% and 24%, respectively. The removal of
      cattle and construction of biogas production units had an additional positive
      effect in that the annual, average emission of greenhouse gases such as methane
      (CH4) and carbon dioxide (CO2) were reduced by an estimated 7.8 and 80.2 tons,
      respectively.

PMID- 22639124
TI  - Divergent spatial patterns in the prevalence of the human immunodeficiency virus
      (HIV) and syphilis in South African pregnant women.
AB  - An analysis of the ecological association between the human immunodeficiency
      virus (HIV) and syphilis was undertaken using joint mapping modelling based on
      data from South African national HIV and syphilis sentinel surveillance surveys
      carried out between 2007 and 2009. The syphilis prevalence, taken as proxy for
      sexual behaviour and increased HIV transmission, was first used with health
      district-level deprivation and population density as a covariate in a HIV
      prevalence spatial regression model and, secondly, together with HIV as a
      bivariate outcome. HIV is more highly prevalent in deprived and populated areas
      than elsewhere, while syphilis has a high prevalence in less deprived and less
      populated areas. Spatially, the HIV prevalence was lowest in the southwestern and
      highest in the northeastern parts of the country. This was in discordance to the
      syphilis prevalence, which revealed negative correlations with HIV prevalence.
      Considerable variations across the districts remained after adjusting for the
      contextual covariate factors. Divergent spatial patterns between HIV and syphilis
      were identified, regarding both observed and unobserved covariate effects. The
      differential disease-specific spatial prevalence patterns may point to
      inconsistent successes in interventions between the two diseases. Overall, the
      results emphasize the need to develop and test plausible aetiological hypotheses
      relating to ecological correlations and causes of the disease-specific
      interjectory between the districts.

PMID- 22639125
TI  - Longevity pattern in the Italian region of Emilia Romagna: a dynamic perspective.
AB  - The pattern of longevity in the Italian north-eastern region of Emilia Romagna
      was investigated at the municipality level, considering a modified version of the
      centenarian rate (CR) in two different periods (1995-1999 and 2005-2009). Due to
      the rareness of such events in small areas, spatio-temporal modelling was used to
      tackle the random variations in the occurrence of long-lived individuals. This
      approach allowed us to exploit the spatial proximity to smooth the observed data,
      as well as controlling for the effects of a set of covariates. As a result,
      clusters of areas characterised by extreme indexes of longevity could be
      identified and the temporal evolution of the phenomenon depicted. A persistence
      of areas of lower and higher occurrences of long-lived subjects was observed
      across time. In particular, mean and median values higher than the regional ones,
      showed up in areas belonging to the provinces of Ravenna and Forli-Cesena, on one
      side spreading out along the Adriatic coast and, on the other stretching into the
      Apennine municipalities of Bologna and Modena. Further, a longitudinal
      perspective was added by carrying out a spatial analysis including the
      territorial patterns of past mortality. We evaluated the effects of the structure
      of mortality on the cohort of long-lived subjects in the second period. The major
      causes of death were considered in order to deepen the analysis of the observed
      geographical differences. The circulatory diseases seem to mostly affect the
      presence of long-lived individuals and a prominent effect of altitude and
      population density also emerges.

PMID- 22639126
TI  - Application of Bayesian geostatistical modeling for the assessment of risk for
      child mortality during the 2008 earthquake in Wenchuan, People's Republic of
      China.
AB  - A Bayesian geostatistical model was used to identify factors related to
      topographical variation in the analysis of mortality risk for children less than
      5 years of age in the 2008 Wenchuan earthquake in the People's Republic of China.
      Epidemiological data from a standardized survey were available from 115 locations
      across the study area. Physical and demographic factors measured directly at the
      township level were examined with respect to risk. The geostatistical model
      explicitly accounted for spatial correlation present in child mortality by
      fitting a Gaussian linear model to the data. Results identified the role of
      several factors in explaining geographical heterogeneity in child mortality and
      show that it was significantly correlated with earthquake intensity, population
      density, migrant labour, and the percentage of collapsed houses.

PMID- 22639127
TI  - Spatial distribution and autocorrelation of infant mortality for three cities in
      Parana state, Brazil.
AB  - Infant mortality (IM), defined as deaths among children one year of age or
      younger, is an indicator of quality of life and of the organisation and quality
      of health services. IM reduction is one of the main goals of healthcare and
      improvements in this area would demonstrate an impact of public services and
      improved living conditions. Knowledge of the geographic distribution of IM can
      provide support for prevention and health maintenance decisions. The objective of
      this study was to analyse the spatial distribution and autocorrelation of IM in
      Maringa, Sarandi and Paicandu, three cities in the Maringa metropolitan area,
      Parana state, Brazil. The coefficients ranged between 6.5 and 18.2, with the
      highest rates found in the outskirts of the fused cities, particularly in the
      demographic expansion areas (DEAs) in Sarandi, with a "high-high" correlation for
      DEAs no. 18 and 19 and a "low-high" for DEA no. 16. In the central area of
      Maringa, represented by DEAs no. 3, 6 and 7, the correlation was "low-low".
      Peripheral DEAs generally show inferior socioeconomic and healthcare conditions.
      These observations make it possible to analyse programme coverage, set
      priorities, define goals and follow-up future changes.

PMID- 22639128
TI  - Combining global positioning system and accelerometer data to determine the
      locations of physical activity in children.
AB  - National trends indicate that children and adolescents are not achieving
      sufficient levels of physical activity. Combining global positioning system (GPS)
      technology with accelerometers has the potential to provide an objective
      determination in locations where youth engage in physical activity. The aim of
      this study was to identify the optimal methods for collecting combined
      accelerometer and GPS data in youth, to best locate where children spend time and
      are physically active. A convenience sample of 24 mid-school children in
      Massachusetts was included. Accelerometers and GPS units were used to quantify
      and locate childhood physical activity over 5 weekdays and 2 weekend days.
      Accelerometer and GPS data were joined by time and mapped with a geographical
      information system (GIS) using ArcGIS software. Data were collected in winter,
      spring, summer in 2009-2010, collecting a total of 26,406 matched datapoints
      overall. Matched data yield was low (19.1% total), regardless of season (winter,
      12.8%; spring, 30.1%; summer, 14.3%). Teacher-provided, pre-charged equipment
      yielded the most matched (30.1%; range: 10.1-52.3%) and greatest average days
      (6.1 days) of data. Across all seasons, children spent most of their time at
      home. Outdoor use patterns appeared to vary by season, with street use increasing
      in spring, and park and playground use increasing in summer. Children spent equal
      amounts of physical activity time at home and walking in the streets. Overall,
      the various methods for combining GPS and accelerometer data provided similarly
      low amounts of combined data. No combined GPS and accelerometer data collection
      method proved superior in every data return category, but use of GIS to map
      joined accelerometer and GPS data can demarcate childhood physical activity
      locations.

PMID- 22639129
TI  - A multi-stage approach to maximizing geocoding success in a large population
      based cohort study through automated and interactive processes.
AB  - To enable spatial analyses within a large, prospective cohort study of nearly
      86,000 adults enrolled in a 12-state area in the southeastern United States of
      America from 2002-2009, a multi-stage geocoding protocol was developed to
      efficiently maximize the proportion of participants assigned an address level
      geographic coordinate. Addresses were parsed, cleaned and standardized before
      applying a combination of automated and interactive geocoding tools. Our full
      protocol increased the non-Post Office (PO) Box match rate from 74.5% to 97.6%.
      Overall, we geocoded 99.96% of participant addresses, with only 5.2% at the ZIP
      code centroid level (2.8% PO Box and 2.3% non-PO Box addresses). One key to
      reducing the need for interactive geocoding was the use of multiple base maps.
      Still, addresses in areas with population density <44 persons/km2 were much more
      likely to require resource-intensive interactive geocoding than those in areas
      with >920 persons/km2 (odds ratio (OR) = 5.24; 95% confidence interval (CI) =
      4.23, 6.49), as were addresses collected from participants during in-person
      interviews compared with mailed questionnaires (OR = 1.83; 95% CI = 1.59, 2.11).
      This study demonstrates that population density and address ascertainment method
      can influence automated geocoding results and that high success in address level
      geocoding is achievable for large-scale studies covering wide geographical areas.

PMID- 22639130
TI  - Cystic echinococcosis in slaughtered cattle in Sardinia: a retrospective
      epidemiological study and spatial analysis.
AB  - Cystic echinococcosis (CE) in cattle was found in 246 out of all 377
      municipalities in Sardinia, Italy. Out of 32,685 bovines slaughtered in Sardinia
      in 2009, 1,360 were found to be positive for CE with a registered average
      prevalence of 4.2%. Of these animals, 896 (66%) had lived on the same farm from
      birth to slaughter, thus linking the infection to the farm with certainty, while
      413 (30%) had lived on two different farms (one transfer) and 51 (4%) on three
      (two transfers). As it was not possible to assess in which farm the animals
      acquired the infection, all farms having kept infected cattle were considered as
      suspected sources of CE infection. Based on this classification, 534 farms were
      listed as definitely infected with a further 495 suspected to also be infected.
      Scan statistics was used with the Bernoulli model to detect and evaluate clusters
      of infected farms and also clusters of "non-cases". For the spatial analysis,
      1,029 farms (534 + 495) were considered as positive with the number of non
      infected farms from which negative results were available (8,457) as controls. A
      most likely cluster was detected at latitude 39.47861 N and longitude 8.58216 E
      in a centroid of 97.92 km radius and a secondary cluster was detected at latitude
      40.58890 N and longitude 8.98400 E in a centroid of 15.44 km radius. To address
      the issue of sensitivity and consistency of the results, we ran multiple scans
      with various max-sizes as this allowed us to achieve more valid, consistent
      results and to highlight the core clusters.

PMID- 22639131
TI  - The Health Resources Allocation Model (HRAM) for the 21st century.
AB  - The Health Resources Allocation Model (HRAM) is an eLearning tool for health
      cadres and scientists introducing basic concepts of sub-national, rational
      district-based health planning and systems thinking under resources constraint.
      HRAM allows the evaluation of resource allocation strategies in relation to key
      outcome measures such as coverage, equity of services achieved and number of
      deaths and disability-adjusted life years (DALYs) prevented. In addition, the
      model takes into account geographical and demographic characteristics and
      populations' health seeking behaviour. It can be adapted to different socio
      ecological and health system settings.

PMID- 22639132
TI  - Health impact assessment of industrial development projects: a spatio-temporal
      visualization.
AB  - Development and implementation of large-scale industrial projects in complex eco
      epidemiological settings typically require combined environmental, social and
      health impact assessments. We present a generic, spatio-temporal health impact
      assessment (HIA) visualization, which can be readily adapted to specific projects
      and key stakeholders, including poorly literate communities that might be
      affected by consequences of a project. We illustrate how the occurrence of a
      variety of complex events can be utilized for stakeholder communication,
      awareness creation, interactive learning as well as formulating HIA research and
      implementation questions. Methodological features are highlighted in the context
      of an iron ore development in a rural part of Africa.

PMID- 22639133
TI  - Enhancing impact: visualization of an integrated impact assessment strategy.
AB  - The environmental impact assessment process is over 40 years old and has
      dramatically expanded. Topics, such as social, health and human rights impact are
      now included. The main body of an impact analysis is generally hundreds of pages
      long and supported by countless technical appendices. For large, oil/gas, mining
      and water resources projects both the volume and technical sophistication of the
      reports has far exceeded the processing ability of host communities. Instead of
      informing and empowering, the reports are abstruse and overwhelming. Reinvention
      is required. The development of a visual integrated impact assessment strategy
      that utilizes remote sensing and spatial analyses is described.

PMID- 22639135
TI  - Type of axial analgesia does not influence time to vaginal delivery in a
      Proportional Hazards Model.
AB  - OBJECTIVE: To create a Proportional Hazards Model of prospective factors
      associated with time-to-vaginal-delivery (TTVD). METHODS: We analyzed a group of
      144 women undergoing childbirth who received one out of two possible axial
      analgesia techniques, to find-out factors associated with TTVD. The patients were
      randomly assigned to receive either a levobupivacaine labor epidural (bolus
      concentration 0.25 % or less; infusion concentration 0.125 % or less) or a
      combined spinal-epidural procedure (morphine 0.20 mg, fentanyl 25 ug and
      hyperbaric bupivacaine 2.5 mg as spinal components) for labor analgesia. The
      factors initially chosen were: mother age, height and weight, parity, gestational
      age, newborn weight, type of labor, analgesic procedure, levobupivacaine and
      fentanyl doses, Bromage scale, pain Numeric Rating Scale, and a satisfaction
      interview. Cesarean section was the censored variable in our model. A systematic
      multivariate Cox regression was performed. RESULTS: Our Final Model stated that
      nulliparous women had 2.5 times more chances of having longer TTVD than
      primiparous (p < 0.001, CI 1.76-3.8), and 3.4 times more (p = 0.015, CI 1.27
      9.25) than multiparous. Women with oxytocin-augmented labor had 2.05 times more
      chances (p = 0.001, CI 1.31-3.22) of having longer TTVD than patients without
      oxytocin. An induced partum had 3.8 times more chances (p < 0.001, CI 2.09-6.8)
      of having longer TTVD compared to a spontaneous partum. CONCLUSION: Parity, labor
      augmentation, induction of labor and fetal weight determine TTVD; axial analgesia
      related factors do not contribute to the model.

PMID- 22639134
TI  - Selectively guanidinylated aminoglycosides as antibiotics.
AB  - The emergence of virulent, drug-resistant bacterial strains coupled with a
      minimal output of new pharmaceutical agents to combat them makes this a critical
      time for antibacterial research. Aminoglycosides are a well-studied, highly
      potent class of naturally occurring antibiotics with scaffolds amenable to
      modification, and therefore, they provide an excellent starting point for the
      development of semisynthetic, next-generation compounds. To explore the potential
      of this approach, we synthesized a small library of aminoglycoside derivatives
      selectively and minimally modified at one or two positions with a guanidine group
      replacing the corresponding amine or hydroxy functionality. Most guanidino
      aminoglycosides showed increased affinity for the ribosomal decoding rRNA site,
      the cognate biological target of the natural products, when compared with their
      parent antibiotics, as measured by an in vitro fluorescence resonance energy
      transfer (FRET) A-site binding assay. Additionally, certain analogues showed
      improved minimum inhibitory concentration (MIC) values against resistant
      bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA).
      An amikacin derivative holds particular promise with activity greater than or
      equal to the parent antibiotic in the majority of bacterial strains tested.

PMID- 22639136
TI  - Risk factors for surgery in patients with tuba-ovarian abscess.
AB  - OBJECTIVE: To determine the factors that increases the need of surgery in the
      treatment of tuba-ovarian abscess. MATERIAL AND METHOD: Fifty patients, who were
      diagnosed with tuba-ovarian abscess between January 2005 and December 2010 at
      Aegean Obstetrics and Gynecology Education and Research Hospital, were reviewed
      retrospectively. Patients were divided into two groups as Group A includes 19
      patients treated medically and Group B includes 31 patients treated surgically.
      Patient characteristics of both groups were compared in terms of risk factors,
      clinical findings, abscess size and length of hospital stay. RESULTS: The mean
      age of the patients was 41.2 +/- 10.4 (range 19-73). A statistically significant
      difference was found between the mean age of the patients (37.4 +/- 8.6) treated
      medically and the mean age of the patients (43.5 +/- 10.8) treated surgically (p
      0.042). The patients treated medically were younger than those treated
      surgically. In addition, there was a statistically significant difference between
      the groups in terms of abscess sizes (p 0.001, 81.7 +/- 38.2 and 43.5 +/- 19.0
      mm, respectively). Accordingly, the size of abscess was larger in the surgical
      treatment group. No significant difference was found between the two groups in
      terms of smoking status and duration of hospital stay (p 0.157, 0.085,
      respectively). Previous attacks of PID, history of minor uterine operation and
      use of IUD's were not different between the groups (p 0.166, 0.490, 0.080,
      respectively). CONCLUSION: Being older in age and having larger abscess size
      increase proceeding to surgery in patients with tuba-ovarian abscess.

PMID- 22639137
TI  - Gastric injuries during gynaecologic laparoscopy.

PMID- 22639139
TI  - [Urology goes to school. Interested schoolchildren test their ability as surgeons
      on a simulator at the German Society for Urology school open day].

PMID- 22639138
TI  - Sport participation in colorectal cancer survivors: an unexplored approach to
      promoting physical activity.
AB  - PURPOSE: Physical activity improves health outcomes in colorectal cancer (CRC)
      survivors, but participation rates are low. One understudied strategy for
      increasing physical activity in CRC survivors may be sport participation. Here,
      we report the sport participation rate, sport preferences, and correlates of
      sport participation among CRC survivors. METHODS: A provincial, population-based
      mailed survey of CRC survivors in Alberta, Canada was performed and included
      measures of sport participation, sport preferences, sport benefits and barriers,
      and medical and demographic variables. RESULTS: A total of 600 CRC survivors
      completed the survey (34 % response rate). Almost a quarter (23.0 %) of CRC
      survivors reported participating in a sport in the past month, with the most
      common sport being golf (58.7 %). In multivariate regression analysis, 33.0 % (p
      = 0.001) of the variance in sport participation was explained by being male (beta
      = 0.12; p = 0.006), in better general health (beta = 0.12; p = 0.006), and >= 5
      years post-diagnosis (beta = 0.09; p = 0.031). The most common barriers to sport
      participation were time, age/agility, and no interest/dislike of sports. The most
      common anticipated benefits of sport participation were improved physical
      fitness, meeting people, and improved health. Over half (57.2 %) of CRC survivors
      were possibly interested in learning about sport participation opportunities.
      CONCLUSIONS: Promotion of sport participation may be a potentially fruitful
      strategy for increasing physical activity in CRC survivors.

PMID- 22639140
TI  - Insertion of transposon in the vicinity of SSK2 confers enhanced tolerance to
      furfural in Saccharomyces cerevisiae.
AB  - Furfural is one of the major inhibitors generated during sugar production from
      cellulosic materials and, as an aldehyde, inhibits various cellular activities of
      microorganisms used, leading to prolonged lag time during ethanologenic
      fermentation. Since Saccharomyces cerevisiae strains tolerant to furfural are of
      great economic benefit in producing bioethanol, much effort to obtain more
      efficient strains continues to be made. In this study, we examined the furfural
      tolerance of transposon mutant strains (Tn 1-5) with enhanced ethanol tolerance
      and found that one of them (Tn 2), in which SSK2 is downregulated at the
      transcriptional level, displayed improved furfural tolerance. Such phenotype was
      abolished by complementation of the entire open reading frame of SSK2, which
      encodes a mitogen-activated protein (MAP) kinase kinase kinase of the high
      osmolarity glycerol (HOG) signaling pathway, suggesting an inhibitory effect of
      SSK2 in coping with furfural stress. Tn 2 showed a significant decrease in the
      intracellular level of reactive oxygen species (ROS) and early and high
      activation of Hog1p, a MAP kinase integral to the HOG pathway in response to
      furfural. The transcriptional levels of CTT1 and GLR1, two of known Hog1p
      downstream target genes whose protein products are involved in reducing ROS, were
      increased by 43 % and 56 % respectively compared with a control strain, probably
      resulting in the ROS decrease. Tn 2 also showed a shortened lag time during
      fermentation in the presence of furfural, resulting from efficient conversion of
      furfural to non-toxic (or less toxic) furfuryl alcohol. Taken together, the
      enhanced furfural tolerance of Tn 2 is suggested to be conferred by the combined
      effect of an early event of less ROS accumulation and a late event of efficient
      detoxification of furfural.

PMID- 22639141
TI  - Identification and characterization of new Delta-17 fatty acid desaturases.
AB  - omega-3 fatty acid desaturase is a key enzyme for the biosynthesis of omega-3
      polyunsaturated fatty acids via the oxidative desaturase/elongase pathways. Here
      we report the identification of three omega-3 desaturases from oomycetes, Pythium
      aphanidermatum, Phytophthora sojae, and Phytophthora ramorum. These new omega-3
      desaturases share 55 % identity at the amino acid level with the known Delta-17
      desaturase of Saprolegnia diclina, and about 31 % identity with the bifunctional
      Delta-12/Delta-15 desaturase of Fusarium monoliforme. The three enzymes were
      expressed in either wild-type or codon optimized form in an engineered
      arachidonic acid producing strain of Yarrowia lipolytica to study their activity
      and substrate specificity. All three were able to convert the omega-6 arachidonic
      acid to the omega-3 eicosapentanoic acid, with a substrate conversion efficiency
      of 54-65 %. These enzymes have a broad omega-6 fatty acid substrate spectrum,
      including both C18 and C20 omega-6 fatty acids although they prefer the C20
      substrates, and have strong Delta-17 desaturase activity but weaker Delta-15
      desaturase activity. Thus, they belong to the Delta-17 desaturase class. Unlike
      the previously identified bifunctional Delta-12/Delta-15 desaturase from F.
      monoliforme, they lack Delta-12 desaturase activity. The newly identified Delta
      17 desaturases could use fatty acids in both acyl-CoA and phospholipid fraction
      as substrates. The identification of these Delta-17 desaturases provides a set of
      powerful new tools for genetic engineering of microbes and plants to produce
      omega-3 fatty acids, such as eicosapentanoic acid and docosahexanoic acid, at
      high levels.

PMID- 22639142
TI  - A targeted gene knockout method using a newly constructed temperature-sensitive
      plasmid mediated homologous recombination in Bifidobacterium longum.
AB  - Bifidobacteria are the main component of the human microflora. We constructed a
      temperature-sensitive (Ts) plasmid by random mutagenesis of the Bifidobacterium
      Escherichia coli shuttle vector pKKT427 using error-prone PCR. Mutant plasmids
      were introduced into Bifidobacterium longum 105-A and, after screening
      approximately 3,000 colonies, candidate clones that grew at 30  degrees C but not
      at 42  degrees C were selected. According to DNA sequence analysis of the Ts
      plasmid, five silent and one missense mutations were found in the repB region.
      The site-directed mutagenesis showed only the missense mutation to be relevant to
      the Ts phenotype. We designated this plasmid pKO403. The Ts phenotype was also
      observed in B. longum NCC2705 and Bifidobacterium adolescentis ATCC15703. Single
      crossover homologous-recombination experiments were carried out to determine the
      relationship between the length of homologous sequences encoded on the plasmid
      and recombination frequency: fragments greater than 1 kb gave an efficiency of
      more than 10(3) integrations per cell. We performed gene knockout experiments
      using this Ts plasmid. We obtained gene knockout mutants of the pyrE region of B.
      longum 105-A, and determined that double-crossover homologous recombination
      occurred at an efficiency of 1.8 %. This knockout method also worked for the
      BL0033 gene in B. longum NCC2705.

PMID- 22639143
TI  - Metallic oxide nanoparticles: state of the art in biogenic syntheses and their
      mechanisms.
AB  - This review presents the syntheses and characterizations of size and morphology,
      as well as the mechanistic aspects, of metallic oxide nanoparticles synthesized
      by biogenic processes. Furthermore, the importance of their biogenic synthesis is
      compared with chemical synthesis, and their applications are discussed from the
      ecological and environmental view points. To our best knowledge, this review
      presents for the first time the synthesis of several biogenic oxide
      nanoparticles, with great applications under the perspective of cost effective
      and eco-friendly points of view.

PMID- 22639144
TI  - Functions, applications and production of 2-O-D-glucopyranosyl-L-ascorbic acid.
AB  - Vitamin C (VC) is an essential nutrient that cannot be synthesized by the human
      body. Due to its extreme instability, various VC derivatives have been developed
      in an attempt to improve stability while retaining the same biological activity.
      One of the most important VC derivatives, 2-O-D-glucopyranosyl-L-ascorbic acid
      (AA-2G), has attracted increasing attention in recent years with a wide range of
      applications in cosmetics, food, and medicine. In this mini-review, we first
      introduce the types and properties of different VC glycosyl derivatives. Next, we
      provide an overview of the functions and applications of AA-2G. Finally, we
      discuss in-depth the current status and future prospects of AA-2G production by
      biotransformation.

PMID- 22639147
TI  - Dihydronaphthalene-fused boron-dipyrromethene (BODIPY) dyes: insight into the
      electronic and conformational tuning modes of BODIPY fluorophores.

PMID- 22639145
TI  - Aspergillus and Penicillium identification using DNA sequences: barcode or MLST?
AB  - Current methods in DNA technology can detect single nucleotide polymorphisms with
      measurable accuracy using several different approaches appropriate for different
      uses. If there are even single nucleotide differences that are invariant markers
      of the species, we can accomplish identification through rapid DNA-based tests.
      The question of whether we can reliably detect and identify species of
      Aspergillus and Penicillium turns mainly upon the completeness of our alpha
      taxonomy, our species concepts, and how well the available DNA data coincide with
      the taxonomic diversity in the family Trichocomaceae. No single gene is yet known
      that is invariant within species and variable between species as would be optimal
      for the barcode approach. Data are published that would make an MLST approach to
      isolate identification possible in the most well-studied clades of Aspergillus
      and Penicillium.

PMID- 22639149
TI  - Determination of fracture toughness of human permanent and primary enamel using
      an indentation microfracture method.
AB  - The purpose of the present study was to examine the fracture toughness and
      Vickers microhardness number of permanent and primary human enamel using the
      indentation microfracture method. Crack resistance and a parameter indirectly
      related to fracture toughness were measured in 48 enamel specimens from 16
      permanent teeth and 12 enamel specimens obtained from six primary teeth. The
      Vickers microhardness number of the middle portion was greater than the upper
      portion in primary enamel. The fracture toughness was highest in the middle
      portion of permanent enamel, because fracture toughness greatly depends upon
      microstructure. These findings suggest that primary teeth are not miniature
      permanent teeth but have specific and characteristic mechanical properties.

PMID- 22639150
TI  - Carbon-centered radicals in gamma-irradiated bone substituting biomaterials based
      on hydroxyapatite.
AB  - Gamma irradiated synthetic hydroxyapatite, bone substituting materials
      NanoBone((r)) and HA Biocer were examined using EPR spectroscopy and compared
      with powdered human compact bone. In every case, radiation-induced carbon
      centered radicals were recorded, but their molecular structures and
      concentrations differed. In compact bone and synthetic hydroxyapatite the main
      signal assigned to the CO(2) (-) anion radical was stable, whereas the signal due
      to the CO(3) (3-) radical dominated in NanoBone((r)) and HA Biocer just after
      irradiation. However, after a few days of storage of these samples, also a CO(2)
      (-) signal was recorded. The EPR study of irradiated compact bone and the
      synthetic graft materials suggest that their microscopic structures are
      different. In FT-IR spectra of NanoBone((r)), HA Biocer and synthetic
      hydroxyapatite the HPO(4) (2-) and CO(3) (2-) in B-site groups are detected,
      whereas in compact bone signals due to collagen dominate.

PMID- 22639151
TI  - Biomimetic CaP coating incorporated with parathyroid hormone improves the
      osseointegration of titanium implant.
AB  - Parathyroid hormone (PTH) is a well-known therapeutic agent for osteoporosis
      treatment, however, the inconvenience of daily administration and side effect
      from systematic administration severely limits its application in clinic. PTH has
      been incorporated into a biomimetic calcium phosphate (CaP) coating via a co
      precipitation method in a modified simulated body fluid. The aim of the current
      study is to evaluate the osseointegration response of PTH incorporated CaP
      coating on titanium implants. Implants with different doses of PTH were inserted
      into tibiae of mice and evaluated by X-ray, micro-CT, histology and back
      scattered scanning electron microscopy. Improved osseointegration of the implants
      loaded with PTH was observed compared to CaP coating only after 28 days of
      implantation in mouse tibiae. Micro-CT analysis showed better bone integration
      around the implant incorporated with PTH. Bone area and bone contact evaluations
      have demonstrated that peri-implant bone regeneration is highly dependent on the
      dosage of PTH incorporated. The higher the PTH content, the more bone formed
      surrounding the implant. Therefore, our results suggest that biomimetic CaP
      coating could be a useful a carrier for PTH local delivery, which results in
      improved bone-to-implant integration.

PMID- 22639152
TI  - Synthesis and evaluation of novel absorptive and antibacterial polyurethane
      membranes as wound dressing.
AB  - Preparation and evaluation of new polyurethane membranes for wound dressing
      application was considered in this work. The membranes were prepared through
      amine curing reaction of epoxy-terminated polyurethane prepolymers and an
      antibacterial epoxy-functional quaternary ammonium compound
      (glycidyltriehtylammonium chloride, GTEACl. To render the prepared membranes to
      be highly absorptive of wound exudates, poly (ethylene glycol) polyols were
      introduced into the polyurethane networks. Evaluation of biocompatibity via both
      MTT assay and direct contact with two different cell lines (fibroblast and
      epidermal keratinocytes) reveled that membranes with appropriate loading of
      GTEACl showed proper biocompatibility. Promising antibacterial activity of the
      prepared membranes against Staphylococcus aureus and Escherichia coli bacteria
      was confirmed by both agar diffusion and shaking flask methods. The membranes
      with balanced crosslink density and ionic groups' concentration possessed
      appropriate hydrophilicity and water vapor transmission rate; therefore, they
      could prevent the accumulation of exudates and decrease the surface inflammation
      in the wounded area.

PMID- 22639153
TI  - Hydrogels of collagen/chondroitin sulfate/hyaluronan interpenetrating polymer
      network for cartilage tissue engineering.
AB  - The network structure of a three-dimensional hydrogel scaffold dominates its
      performance such as mechanical strength, mass transport capacity, degradation
      rate and subsequent cellular behavior. The hydrogels scaffolds with
      interpenetrating polymeric network (IPN) structure have an advantage over the
      individual component gels and could simulate partly the structure of native
      extracellular matrix of cartilage tissue. In this study, to develop perfect
      cartilage tissue engineering scaffolds, IPN hydrogels of collagen/chondroitin
      sulfate/hyaluronan were prepared via two simultaneous processes of collagen self
      assembly and cross linking polymerization of chondroitin sulfate-methacrylate
      (CSMA) and hyaluronic acid-methacrylate. The degradation rate, swelling
      performance and compressive modulus of IPN hydrogels could be adjusted by varying
      the degree of methacrylation of CSMA. The results of proliferation and
      fluorescence staining of rabbit articular chondrocytes in vitro culture
      demonstrated that the IPN hydrogels possessed good cytocompatibility.
      Furthermore, the IPN hydrogels could upregulate cartilage-specific gene
      expression and promote the chondrocytes secreting glycosaminoglycan and collagen
      II. These results suggested that IPN hydrogels might serve as promising hydrogel
      scaffolds for cartilage tissue engineering.

PMID- 22639155
TI  - Molecular biology of glioma.
AB  - Glioblastoma (GBM) is the most aggressive form of glioma. Despite ceaseless
      efforts by researchers and physicians to find new therapeutic strategies, there
      have been no significant advances in the treatment of GBMs for several decades
      and most patients with GBM die within one and half years of diagnosis.
      Undoubtedly, one reason for this is the insufficient understanding of the
      initiation and progression of GBMs at the molecular level. However, recent
      information regarding the genetic and epigenetic alterations and the microRNAs
      that are aberrantly activated or inactivated in GBMs has helped elucidate the
      formation of GBM in more detail. Here, we describe recent advances in the
      understanding of the biology of GBMs.

PMID- 22639154
TI  - Effect of the calcium to phosphorus ratio on the setting properties of calcium
      phosphate bone cements.
AB  - alpha-Tricalcium phosphate (alpha-TCP) has become the main reactant of most
      experimental and commercial ceramic bone cements. It has calcium-to-phosphorus
      (Ca/P) ratio of 1.50. The present study expands and reports on the
      microstructures and mechanical properties of calcium phosphate (CP) cements
      containing sintered monolithic reactants obtained in the interval 1.29 < Ca/P <
      1.77. The study focuses on their cement setting and hardening properties as well
      as on their microstructure and crystal phase evolution. The results showed that:
      (a) CP-cements made with reactants with Ca/P ratio other than 1.50 have longer
      setting and lower hardening properties; (b) CP-cements reactivity was clearly
      affected by the Ca/P ratio of the starting reactant; (c) reactants with Ca/P <
      1.50 were composed of several phases, calcium pyrophosphate and alpha- and beta
      TCP. Similarly, reactants with Ca/P > 1.50 were composed of alpha-TCP,
      tetracalcium phosphate and hydroxyapatite; (d) only the reactant with Ca/P = 1.50
      was monophasic and was made of alpha-TCP, which transformed during the setting
      into calcium deficient hydroxyapatite; (e) CP-cements developed different crystal
      microstructures with specific features depending on the Ca/P ratio of the
      starting reactant.

PMID- 22639156
TI  - Recent surgical management of gliomas.
AB  - Refinement of neurosurgical technique has enabled safer operations with more
      aggressive outcomes. One cornerstone of modern-day practice is the utilization of
      intraoperative stimulation mapping. In addition to identifying critical motor
      pathways, this technique can be adapted to reliable identify language pathways,
      as well. Given the individual variability of cortical language localization, such
      awake language mapping is essential to minimize language deficits following tumor
      resection. Our experience suggests that cortical language mapping is a safe and
      efficient adjunct to optimize tumor resection while preserving essential language
      sites, even in the setting of negative mapping data. However, the value of
      maximizing glioma resections remains surprisingly unclear, as there is no general
      consensus in the literature regarding the efficacy of extent of glioma resection
      in improving patient outcome. While the importance of resection in obtaining
      tissue diagnosis and to alleviate symptoms is clear, a lack of Class I evidence
      prevents similar certainty in assessing the influence of extent of resection.
      Beyond an analysis of modern intraoperative mapping techniques, we examine every
      major clinical publication since 1990 on the role of extent of resection in
      glioma outcome. The mounting evidence suggests that, despite persistent
      limitations in the quality of available studies, a more extensive surgical
      resection is associated with longer life expectancy for both low-grade and high
      grade gliomas.

PMID- 22639157
TI  - Recent medical management of glioblastoma.
AB  - This chapter contains an overview of standard of care and experimental
      chemotherapy treatments for glioblastoma multiforme (GBM). We discuss the role of
      alkylating agents, focusing primarily on temozolomide (TMZ) which, in combination
      with radiation therapy, is part of the standard of care treatment for newly
      diagnosed GBM. TMZ has proven both well tolerated and effective in prolonging
      patient survival, but tumor recurrence remains the rule. We review the
      development and use of molecularly targeted agents, low molecular weight kinase
      inhibitors and monoclonal antibodies that interrupt the signaling pathways
      exploited by tumors to grow, migrate and avoid apoptosis.

PMID- 22639158
TI  - Basic concepts in glioma immunology.
AB  - Glioblasotmas are the most common primary central nervous system tumor and
      typically have a dismal prognosis. Immunotherapy has been a promising
      experimental treatment. Understanding brain tumor immunobiology is critical to
      designing glioblasotma immunotherapies. In this chapter, we review aspects of
      basic immunology and neuro-immunology. The antigenic underpinnings of brain tumor
      immunotherapy including glioma-associated and glioma-specific antigens are
      discussed. Finally, the molecular and cellular facets of glioma-mediated
      immunosuppression are outlined. The role of multiple cell types (glioma cells,
      glioma-infiltrating monocytes, regulatory T cells and myeloid derived suppressor
      cells) in mediating local and systemic immunosuppression in glioma patients is
      evaluated.

PMID- 22639159
TI  - Mechanisms of immune evasion by gliomas.
AB  - A major contributing factor to glioma development and progression is its ability
      to evade the immune system. This chapter will explore the mechanisms utilized by
      glioma to mediate immunosuppression and immune evasion. These include intrinsic
      mechanisms linked to its location within the brain and interactions between
      glioma cells and immune cells. Lack of recruitment of naive effector immune cells
      perhaps accounts for most of the immune suppression mediated by these tumor
      cells. This is enhanced by increased recruitment of microglia which resemble
      immature antigen presenting cells that are unable to support T-cell mediated
      immunity. Furthermore, secreted factors like TGF-beta, COX-2 and IL-10, altered
      costimulatory molecules and inhibition of STAT-3 all contribute to the
      recruitment and expansion of regulatory T cells, which further modulate the
      immunosuppressive environment of glioma. In light of these findings, multiple
      immunotherapeutic treatment modalities are currently being explored.

PMID- 22639160
TI  - Glioma antigen.
AB  - Because several antigenic peptides of human tumors that are recognized by T
      lymphocytes have been identified, immune responses against cancer can now be
      artificially manipulated. Furthermore, since T-lymphocytes have been found to
      play an important role in the rejection of tumors by the host and also to have
      antigen-specific proliferative potentials and memory mechanisms, T-lymphocytes
      are thought to play a central role in cancer vaccination. Although
      multidisciplinary therapies have been attempted for the treatment of gliomas, the
      results remain unsatisfactory. For the development of new therapies against
      gliomas, it is required to identify tumor antigens as targets for specific
      immunotherapy. In this chapter, recent progress in research on glioma antigens is
      described.

PMID- 22639161
TI  - Cytokine therapy.
AB  - Cytokines are a heterogeneous group of soluble small polypeptides or
      glycoproteins, which exert pleiotropic and redundant effects that promote growth,
      differentiation and activation of normal cells. Cytokines can have either pro- or
      anti-inflammatory activity and immunosuppressive activity, depending on the
      microenvironments. The tumor microenvironment consists of a variable combination
      of tumor cells, endothelial cells and infiltrating leukocytes, such as
      macrophages, T-lymphocytes, natural killer (NK) cells, B cells and antigen
      presenting cells (APCs). Cytokine production acts as a means of communication in
      the tumor microenvironment. In this article, we review the cross-talk between
      cytokines in the tumor environment and the cytokine therapies that have been used
      till date for glioma treatment.

PMID- 22639162
TI  - Immunotherapeutic approach with oligodeoxynucleotides containing CpG motifs (CpG
      ODN) in malignant glioma.
AB  - Bacterial DNA and synthetic oligodeoxynucleotides containing CpG motifs (CpG
      ODNs) are strong activators of both innate and specific immunity, driving the
      immune response towards the Th1 phenotype. In cancer patients, CpG-ODNs can be
      used to activate the innate immunity and trigger a tumor-specific immune
      response. Several clinical trials are on-going worldwide in various cancers. In
      this chapter, we will focus on the potential applications of CpG-ODNs in glioma.
      So far, CpG-ODN has mainly been used by intratumoral injections. Indeed, human
      gliomas display a locally invasive pattern of growth and rarely metastasize,
      making local treatment clinically relevant.

PMID- 22639163
TI  - Adoptive cell transfer therapy for malignant gliomas.
AB  - To date, various adoptive immunotherapies have been attempted for treatment of
      malignant gliomas using nonspecific and/or specific effector cells. Since the
      late 1980s, with the development of rIL-2, the efficacy of lymphokine-activated
      killer (LAK) cell therapy with or without rIL-2 for malignant gliomas had been
      tested with some modifications in therapeutic protocols. With advancements in
      technology, ex vivo expanded tumor specific cytotoxic T-lymphocytes (CTL) or
      those lineages were used in clinical trials with higher tumor response rates. In
      addition, combinations of those adoptive cell transfer using LAK cells, CTLs or
      natural killer (NK) cells with autologous tumor vaccine (ATV) therapy were
      attempted. Also, a strategy of high-dose (or lymphodepleting) chemotherapy
      followed by adoptive cell transfer has been drawing attentions recently. The most
      important role of these clinical studies using cell therapy was to prove that
      these ex vivo expanded effector cells could kill tumor cells in vivo. Although
      recent clinical results could demonstrate radiologic tumor shrinkage in a number
      of cases, cell transfer therapy alone has been utilized less frequently, because
      of the high cost of ex vivo cell expansion, the short duration of antitumor
      activity in vivo, and the recent shift of interest to vaccine immunotherapy.
      Nevertheless, NK cell therapy using specific feeder cells or allergenic NK cell
      lines have potentials to be a good choice of treatment because of easy ex vivo
      expansion and their efficacy especially when combined with vaccine therapy as
      they are complementary to each other. Also, further studies are expected to
      clarify the efficacy of the high-dose chemotherapy followed by a large scale cell
      transfer therapy as a new therapeutic strategy for malignant gliomas.

PMID- 22639164
TI  - Monoclonal antibody therapy for malignant glioma.
AB  - Monoclonal antibody (mAb) therapy is a rapidly evolving treatment immunotherapy
      modality for malignant gliomas. Many studies have provided evidence that the
      blood brain barrier-both at baseline and in the context of malignancy-is
      permissive for mAbs, thus providing a rationale for their use in treating
      intracranial malignancy. Furthermore, techniques such as convection enhanced
      delivery (CED) are being implemented to maximize exposure of tumor cells to mAb
      therapy. The mechanisms and designs of mAbs are widely varying, including unarmed
      immunoglobulins as well as immunoglobulins conjugated to radioisotopes,
      biological toxins, boronated dendrimers and immunoliposomes. The very structure
      of the immunoglobulin molecule has also been manipulated to generate a diverse
      armamentarium including single-chain Fv, bispecific T-cell engagers and chimeric
      antigen receptors. The targeted neutralization capacity of mAbs has been employed
      to modulate the immunologic milieu in hopes of optimizing other immunotherapy
      platforms. Many clinical trials have evaluated these mAb strategies to treat
      malignant gliomas, and the implementation of mAb therapy seems imminent and
      optimistic.

PMID- 22639165
TI  - Animal models for vaccine therapy.
AB  - Animal models are important for defining paradigms of tumor immunology and for
      evaluating therapeutic efficacy of immunotherapy. Many animal models have been
      used for evaluating in vivo characteristics of malignant gliomas and their
      responses to therapy. No animal model, however, is perfect because malignant
      glioma has a very heterogeneous biological behavior. There are so many parallels
      between mouse and human immunology, but there are significant discrepancies in
      immune system. Animal models for vaccine therapy can be classified as
      transplantable tumor models and models of spontaneous tumor in genetically
      engineered animals. Although transplantable tumor models have been used to test
      immunotherapeutic efficacy and remain a mainstay in study of brain tumor
      immunology, a lot of tumor vaccines that look promising in experimental animals
      have turned out to be ineffective clinically. Recent advances of laboratory
      techniques and understanding of genetic and molecular characteristics of gliomas
      allows for animal models of gliomas with similar biologic characteristics. Well
      designed glioma models that accurately reflect the biology, pathology and
      clinical behaviors of human gliomas can provide more useful preclinical
      informations to predict clinical efficacy of novel immunotherapies and cancer
      vaccines.

PMID- 22639166
TI  - Immunogene therapy.
AB  - Antigenic differences between normal and malignant cells of the cancer patient
      form the rationale for clinical immunotherapeutic strategies. Because the
      antigenic phenotype of neoplastic cells varies widely among different cells
      within the same malignant cell-population, immunization with a vaccine that
      stimulates immunity to the broad array of tumor antigens expressed by the cancer
      cells is likely to be more efficacious than immunization with a vaccine for a
      single antigen. A vaccine prepared by transfer of DNA from the tumor into a
      highly immunogenic cell line can encompass the array of tumor antigens that
      characterize the patient's neoplasm. Poorly immunogenic tumor antigens,
      characteristic of malignant cells, can become strongly antigenic if they are
      expressed by highly immunogenic cells. A DNA-based vaccine was prepared by
      transfer of genomic DNA from a breast cancer that arose spontaneously in a C3H/He
      mouse into a highly immunogenic mouse fibroblast cell line, where genes
      specifying tumor-antigens were expressed. The fibroblasts were modified in
      advance of DNA-transfer to secrete an immune augmenting cytokine and to express
      allogeneic MHC Class I-determinants. In an animal model of breast cancer
      metastatic to the brain, introduction of the vaccine directly into the tumor bed
      stimulated a systemic cellular antitumor immune response measured by two
      independent in vitro assays and prolonged the lives of the tumor-bearing mice.
      Furthermore, using antibodies against the various T-cell subsets, it was
      determined that the systemic cellular antitumor immunity was mediated by CD8+,
      CD4+ and NK/LAK cells. In addition an enrichment strategy has also been developed
      to increase the proportion of immunotherapeutic cells in the vaccine which has
      resulted in the development of enhanced antitumor immunity. Finally regulatory T
      cells (CD4+CD25+Fox p3+-positive) were found to be relatively deficient in the
      spleen cells from the tumor-bearing mice injected intracerebrally with the
      enriched vaccine. The application of DNA-based genomic vaccines for the treatment
      of a variety of brain tumors is being explored.

PMID- 22639167
TI  - Peptide vaccine.
AB  - Current combinations of surgical therapy, radiotherapy and chemotherapy regimens
      do not significantly improve long-term survival of the patients with malignant
      glioma. Cancer immunotherapy against malignant glioma is a potentially new
      therapeutic strategy that primes a patient's immune system to attack glioma
      cells. Peptide-based vaccination appears promising as an approach to successfully
      induce an antineoplastic immune response, produce clinical response and prolong
      survival in patients with malignant glioma without major side effects. In this
      chapter, clinical progress is reviewed in developing peptide-based vaccinations
      for malignant glioma to date.

PMID- 22639168
TI  - Active immunotherapy: oncolytic virus therapy using HSV-1.
AB  - Conditionally replicating herpes simplex viruses Type 1 (HSV-1) are promising
      therapeutic agents for glioma. They can replicate in situ, spread and exhibit
      oncolytic activity via a direct cytocidal effect. In addition, specific antitumor
      immunity is effectively induced in the course of oncolytic activities. G47Delta
      is a genetically engineered HSV-1 with triple mutations that realized augmented
      viral replication in tumor cells, strong induction of antitumor immunity and
      enhanced safety in normal tissues. A clinical trial of G47Delta in patients with
      recurrent glioblastoma has started in 2009. One of the advantages of HSV-1 is its
      capacity to incorporate large and/or multiple transgenes within the viral genome.
      In preclinical studies, "arming" of an oncolytic HSV-1 with transgenes encoding
      immunomodulatory molecules, such as interleukin 12, has been shown to greatly
      augment the efficacy of oncolytic HSV-1 therapy. Oncolytic virus therapy using
      HSV-1 may be a useful treatment for glioma that can also function as an efficient
      in situ tumor vaccination.

PMID- 22639169
TI  - Dendritic cell vaccines.
AB  - Despite progress in brain tumor therapy, the prognosis of malignant glioma
      patients remains dismal. Among the new treatments currently being investigated,
      immunotherapy is theoretically very attractive since it offers the potential for
      high tumor-specific cytotoxicity. Increasing numbers of reports demonstrate that
      systemic immunotherapy using dendritic cells is capable of inducing an antiglioma
      response. Therefore, dendritic cell-based immunotherapy could be a new treatment
      modality for patients with glioma. In this chapter, we will discuss the
      implications of these findings for glioma therapy, reviewing current literature
      on dendritic cell-based glioma immunotherapy. We will overview the role of
      dendritic cells in immunobiology, the central nervous system and tumor
      immunology, before outlining dendritic cell therapy results in clinical trials
      and future directions. Dendritic cell-based immunotherapy strategies appear
      promising as an approach to successfully induce an antitumor immune response in
      patients with glioma, where it seems to be safe and without major side effects.
      The development of methods for manipulating dendritic cells for the purpose of
      vaccination will enhance the clinical usefulness of these cells for biotherapy.
      Its efficacy should be further determined in randomized, controlled clinical
      trials.

PMID- 22639170
TI  - Antigen-receptor gene-modified T cells for treatment of glioma.
AB  - Immunological effector cells and molecules have been shown to access intracranial
      tumor sites despite the existence of blood brain barrier (BBB) or
      immunosuppressive mechanisms associated with brain tumors. Recent progress in T
      cell biology and tumor immunology made possible to develop strategies of tumor
      associated antigen-specific immunotherapeutic approaches such as vaccination with
      defined antigens and adoptive T-cell therapy with antigen-specific T cells
      including gene-modified T cells for the treatment of patients with brain tumors.
      An array of recent reports on the trials of active and passive immunotherapy for
      patients with brain tumors have documented safety and some preliminary clinical
      efficacy, although the ultimate judgment for clinical benefits awaits rigorous
      evaluation in trials of later phases. Nevertheless, treatment with lymphocytes
      that are engineered to express tumor-specific receptor genes is a promising
      immunotherapy against glioma, based on the significant efficacy reported in the
      trials for patients with other types of malignancy. Overcoming the relative
      difficulty to apply immunotherapeutic approach to intracranial region, current
      advances in the understanding of human tumor immunology and the gene-therapy
      methodology will address the development of effective immunotherapy of brain
      tumors.

PMID- 22639171
TI  - Glioma stem cell research for the development of immunotherapy.
AB  - Malignant gliomas are characterized by its invasiveness and dissemination,
      resulting in frequent tumor recurrence after surgical resection and/or
      conventional chemotherapy and radiation therapy. Various strategies of active and
      passive immunotherapy in developing stages have shown promise to increase patient
      survival time with little severe side effects. In recent years, glioma stem cells
      had been isolated from patient tumor specimens. Biochemical and biological
      characterization of these cancer initiating cells implicated their critical roles
      in cancer growth, malignancy and resistance to conventional treatments. In this
      chapter, we review recent research progress in targeting brain cancer using
      neural stem cells delivered cytotoxic factors and immune regulation factor,
      dendritic cell based vaccination, with special emphasis on targeting glioma stem
      cells. We present evidence supporting the notion that glioma stem cells may be
      preferred therapeutic targets not only for conventional therapies, but also for
      immunotherapies. Future progress in glioma stem cell research may fundamentally
      improve the prospect of malignant glioma treatments.

PMID- 22639172
TI  - Cytokine response in patients with chronic infections caused by Staphylococcus
      aureus strains and diversification of their Agr system classes.
AB  - This study aimed to describe the levels of circulating cytokine levels produced
      by Th lymphocytes (IFN-gamma, IL-4, IL-10, IL-17A), as well as the levels of
      cytokines produced by monocytes/macrophages (TNF-alpha, IL-1beta, IL-12), in
      patients with chronic infections caused by Staphylococcus aureus strains,
      particularly in the context of the diversification of their Agr system classes.
      The studies were conducted on adult patients, including 50 patients with chronic
      suppurative dermatitis, 40 patients with chronic infections of the upper
      respiratory tract and 25 healthy individuals (control group). Blood serum
      cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). S.
      aureus was detected in cultures of suppurative dermal exudates or of pharyngeal
      smears. Classes of Agr systems in the S. aureus strains were identified using
      polymerase chain reaction (PCR). In both groups of patients, on average, levels
      of IFN-gamma were doubled, while levels of IL-17A were increased by 2.5-fold,
      which, however, was not accompanied by increased levels of TNF-alpha or IL-12.
      The data indicate that the development of S. aureus infection among the studied
      patients was linked to an impoverished cytokine response of
      monocytes/macrophages, while that induced by the pathogen lymphocytes Th17/Th1
      may be responsible for promotion of the chronic inflammatory response. In
      parallel, no quantitative or qualitative differences were disclosed between
      cytokine responses manifested by subgroups of patients infected with S. aureus
      strains belonging to class IV Agr, as compared to patients infected with strains
      of classes I to III Agr. Nevertheless, in the patients, strains belonging to
      class IV Agr prevailed, which points to the preferential relationship between the
      class and the pathogenicity of S. aureus.

PMID- 22639173
TI  - Raman spectroscopic analysis of the clonal and horizontal spread of CTX-M-15
      producing Klebsiella pneumoniae in a neonatal intensive care unit.
AB  - Nosocomial outbreaks of extended-spectrum beta-lactamase (ESBL)-producing
      Klebsiella pneumoniae are an increasing concern in neonatal intensive care units
      (NICUs). We describe an outbreak of ESBL-producing K. pneumoniae that lasted 5
      months and affected 23 neonates in our NICU. Proton pump inhibitor and extended
      spectrum cephalosporin exposure were significantly associated with the risk of
      ESBL-producing K. pneumoniae colonisation and/or infection. Thirty isolates
      recovered from clinical, screening and environmental samples in the NICU were
      studied by means of Raman spectroscopy, pulsed-field gel electrophoresis and
      repetitive extragenic palindromic polymerase chain reaction (rep-PCR). The Raman
      clustering was in good agreement with the results of the other two molecular
      methods. Fourteen isolates belonged to the Raman clone 1 and 16 to the Raman
      clone 3. Molecular analysis showed that all the strains expressed SHV-1
      chromosomal resistance, plasmid-encoded TEM-1 and CTX-M-15 beta-lactamases.
      Incompatibility groups of plasmid content identified by PCR-based replicon typing
      indicated that resistance dissemination was due to the clonal spread of K.
      pneumoniae and horizontal CTX-M-15 gene transfer between the two clones.

PMID- 22639174
TI  - One-step sample preparation of positive blood cultures for the direct detection
      of methicillin-sensitive and -resistant Staphylococcus aureus and methicillin
      resistant coagulase-negative staphylococci within one hour using the automated
      GenomEra CDXTM PCR system.
AB  - A method for the rapid detection of methicillin-sensitive and -resistant
      Staphylococcus aureus (MSSA and MRSA, respectively) and methicillin-resistant
      coagulase-negative staphylococci (MRCoNS) with a straightforward sample
      preparation protocol of blood cultures using an automated homogeneous polymerase
      chain reaction (PCR) assay, the GenomEraTM MRSA/SA (Abacus Diagnostica Oy, Turku,
      Finland), is presented. In total, 316 BacT/Alert (bioMerieux, Marcy l'Etoile,
      France) and 433 BACTEC (Becton Dickinson, Sparks, MD, USA) blood culture bottles
      were analyzed, including 725 positive cultures containing Gram-positive cocci in
      clusters (n = 419) and other Gram stain forms (n = 361), as well as 24 signal-
      and growth-negative bottles. Detection sensitivities for MSSA, MRSA, and MRCoNS
      were 99.4 % (158/159), 100.0 % (9/9), and 99.3 % (132/133), respectively. One
      false-positive MRSA result was detected from a non-staphylococci-containing
      bottle, yielding a specificity of 99.8 %. The lowest detectable amount of viable
      cells in the blood culture sample was 4 * 10(4) CFU/mL. The results were
      available within one hour after microbial growth detection and the two-step, time
      resolved fluorometric (TRF) measurement mode employed by the GenomEra CDXTM
      instrument showed no interference from blood, charcoal, or culture media. The
      method described lacks all sample purification steps and allows reliable and
      simplified pathogen detection also in clinical microbiology laboratory settings
      without specialized molecular microbiology competence.

PMID- 22639175
TI  - Direct identification of bacteria from charcoal-containing blood culture bottles
      using matrix-assisted laser desorption/ionisation time-of-flight mass
      spectrometry.
AB  - Several protocols for direct matrix-assisted laser desorption/ionisation time-of
      flight mass spectrometry (MALDI-TOF MS) from positive blood cultures are
      currently used to speed up the diagnostic process of bacteraemia. Identification
      rates are high and results are accurate for the BACTECTM system and for charcoal
      free bottles. Only a few studies have evaluated protocols for charcoal-containing
      BacT/ALERT bottles reaching substantially lower identification rates. We
      established a new protocol for sample preparation from aerobic and anaerobic
      positive charcoal-containing BacT/ALERT blood culture bottles and measured the
      protein profiles (n = 167). Then, we integrated this protocol in the routine
      workflow of our laboratory (n = 212). During the establishment of our protocol,
      74.3 % of bacteria were correctly identified to the species level, in 23.4 %, no
      result and in 2.4 %, a false identification were obtained. Reliable criteria for
      correct species identification were a score value >=1.400 and a best match on
      rank 1-3 of the same species. Identification rates during routine workflow were
      77.8 % for correct identification, 20.8 % for not identified samples and 1.4 %
      for discordant identification. In conclusion, our results indicate that MALDI-TOF
      MS is possible, even from charcoal-containing blood cultures. Reliable criteria
      for correct species identification are a score value >=1.400 and a best match on
      rank 1-3 of a single species.

PMID- 22639177
TI  - Ageing of internal models: from a continuous to an intermittent proprioceptive
      control of movement.
AB  - To control the sensory-motor system, internal models mimic the transformations
      between motor commands and sensory signals. The present study proposed to assess
      the effects of physiological adult ageing on the proprioceptive control of
      movement and the related internal models. To this aim, one group of young adults
      and one group of older adults performed an ankle contralateral concurrent
      matching task in two speed conditions (self-selected and fast). Error, temporal
      and kinematic variables were used to assess the matching performance. The results
      demonstrated that older adults used a different mode of control as compared to
      the young adults and suggested that the internal models of proprioceptive control
      were altered with ageing. Behavioural expressions of these alterations were
      dependent upon the considered condition of speed. In the self-selected speed
      condition, this alteration was expressed through an increased number of
      corrective sub-movements in older adults as compared to their young peers. This
      strategy enabled them to reach a level of end-point performance comparable to the
      young adults' performance. In the fast speed condition, older adults were no more
      able to compensate for their impaired internal models through additional
      corrective sub-movements and therefore decreased their proprioceptive control
      performance. These results provided the basis for a model of proprioceptive
      control of movement integrating the internal models theory and the continuous and
      intermittent modes of control. This study also suggested that motor control was
      affected by the frailty syndrome, i.e. a decreased resistance to stressors, which
      characterises older adults. 

PMID- 22639176
TI  - Late-life enalapril administration induces nitric oxide-dependent and independent
      metabolic adaptations in the rat skeletal muscle.
AB  - Recently, we showed that administration of the angiotensin-converting enzyme
      inhibitor enalapril to aged rats attenuated muscle strength decline and mitigated
      apoptosis in the gastrocnemius muscle. The aim of the present study was to
      investigate possible mechanisms underlying the muscle-protective effects of
      enalapril. We also sought to discern the effects of enalapril mediated by nitric
      oxide (NO) from those independent of this signaling molecule. Eighty-seven male
      Fischer 344 * Brown Norway rats were randomly assigned to receive enalapril (n =
      23), the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME;
      n = 22), enalapril + L-NAME (n = 19), or placebo (n = 23) from 24 to 27 months of
      age. Experiments were performed on the tibialis anterior muscle. Total NOS
      activity and the expression of neuronal, endothelial, and inducible NOS isoforms
      (nNOS, eNOS, and iNOS) were determined to investigate the effects of enalapril on
      NO signaling. Transcript levels of tumor necrosis factor-alpha (TNF-alpha) and
      peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha)
      were assessed to explore actions of enalapril on inflammation and mitochondrial
      biogenesis, respectively. Protein expression of energy-sensing and insulin
      signaling mediators, including protein kinase B (Akt-1), phosphorylated Akt-1
      (pAkt-1), mammalian target of rapamycin (mTOR), AMP-activated protein kinase
      subunit alpha (AMPKalpha), phosphorylated AMPKalpha (pAMPKalpha), and the glucose
      transporter GLUT-4, was also determined. Finally, the generation of hydrogen
      peroxide (H2O2) was quantified in subsarcolemmal (SSM) and intermyofibrillar
      (IFM) mitochondria. Enalapril increased total NOS activity, which was prevented
      by L-NAME co-administration. eNOS protein content was enhanced by enalapril, but
      not by enalapril + L-NAME. Gene expression of iNOS was down-regulated by
      enalapril either alone or in combination with L-NAME. In contrast, protein levels
      of nNOS were unaltered by treatments. The mRNA abundance of TNF-alpha was reduced
      by enalapril relative to placebo, with no differences among any other group. PCG
      1alpha gene expression was unaffected by enalapril and lowered by enalapril + L
      NAME. No differences in protein expression of Akt-1, pAkt-1, AMPKalpha,
      pAMPKalpha, or GLUT-4 were detected among groups. However, mTOR protein levels
      were increased by enalapril compared with placebo. Finally, all treatment groups
      displayed reduced SSM, but not IFM H2O2 production relative to placebo. Our data
      indicate that enalapril induces a number of metabolic adaptations in aged
      skeletal muscle. These effects result from the concerted modulation of NO and
      angiotensin II signaling, rather than from a dichotomous action of enalapril on
      the two pathways. Muscle protection by enalapril administered late in life
      appears to be primarily mediated by mitigation of oxidative stress and pro
      inflammatory signaling.

PMID- 22639179
TI  - Incorporation of boron in the walls of an "all-carbon" cyclophane: a novel
      approach to Lewis acidic macrocycles.
AB  - A p-doped conjugated cyclophane! The six boron atoms of the bora-cyclophane (see
      picture) recently reported by Chen and Jakle team up to impart a set of unique
      properties to this novel macrocycle. In particular, this macrocycle undergoes six
      consecutive reversible reductions to afford the hexaanion. It also binds up to
      six small nucleophilic anions, a process that quenches the fluorescence of the
      ring and changes its character to electron-rich.

PMID- 22639178
TI  - A botanical containing freeze dried acai pulp promotes healthy aging and reduces
      oxidative damage in sod1 knockdown flies.
AB  - Superoxide dismutase 1 (SOD1), a critical enzyme against oxidative stress, is
      implicated in aging and degenerative diseases. We previously showed that a
      nutraceutical containing freeze-dried acai pulp promotes survival of flies fed a
      high-fat diet or sod1 knockdown flies fed a standard diet. Here, we investigated
      the effect of acai supplementation initiated at the early or late young adulthood
      on lifespan, physiological function, and oxidative damage in sod1 knockdown
      flies. We found that Acai supplementation extended lifespan even when started at
      the age of 10 days, which is the time shortly before the mortality rate of flies
      accelerated. Life-long acai supplementation increased lifetime reproductive
      output in sod1 knockdown flies. Our molecular studies indicate that acai
      supplementation reduced the protein levels of genes involved in oxidative stress
      response, cellular growth, and nutrient metabolism. Acai supplementation also
      affected the protein levels of ribosomal proteins. In addition, acai
      supplementation decreased the transcript levels of genes involved in oxidative
      stress response and gluconeogenesis, while increasing the transcript levels of
      mitochondrial biogenesis genes. Moreover, acai supplementation reduced the level
      of 4-hydroxynonenal-protein adducts, a lipid peroxidation marker. Our findings
      suggest that acai supplementation promotes healthy aging in sod1-deficient flies
      partly through reducing oxidative damage, and modulating nutrient metabolism and
      oxidative stress response pathways. Our findings provide a foundation to further
      evaluate the viability of using acai as an effective dietary intervention to
      promote healthy aging and alleviate symptoms of diseases with a high level of
      oxidative stress. 

PMID- 22639180
TI  - How to investigate and treat: headache and hyperprolactinemia.
AB  - Hyperprolactinemia is a condition characterised by an increase of prolactin blood
      levels (more than 100-200 ng/ml). It is the most common endocrine disorder of the
      hypothalamic-pituitary axis. The clinical characteristics of the headache
      hyperprolactinemia-hypophyseal-adenoma association are discussed, the various
      diagnostic and treatment possibilities are explored and the etiology of the
      headache is considered in the light of several pathogenetic possibilities. We
      present two cases. (1) A 35-year-old woman suffering from chronic tension-type
      headache interspersed with occasional episodes of migraine without aura (as
      defined by the International Headache Society criteria). She had also suffered
      menstrual cycle alterations since the age of 16. At the age of 30 she developed
      amenorrhea with hyperprolactinemia. Computed tomography (CT) and magnetic
      resonance imaging (MRI) scans revealed a median-left intrasellar mass. Treatment
      with cabergoline resulted in complete resolution of both types of headache and
      the menstrual cycle and prolactin levels returned to normal. The therapy also
      reduced the volume of the tumour. (2) The second case relates to a 47-year-old
      man who had been suffering from tension-type headaches for almost 3 months. The
      patient had never previously suffered from headaches. CT and MRI scans showed a
      large sellar and suprasellar lesion with raised serum prolactin levels. Treatment
      with cabergoline had significantly reduced the prolactin levels and had also
      improved the patient's headaches. High-resolution CT, with and without contrast,
      or MRI is necessary to visualise microprolactinomas (and other sellar lesions)
      and confirm the diagnosis.

PMID- 22639181
TI  - Integrative oncology: managing cancer pain with complementary and alternative
      therapies.
AB  - For the projected 1,638,910 patients with a diagnosis of cancer this year, the
      great majority of them (75-90 %) will experience cancer-related pain. A growing
      number of these patients will turn to complementary and alternative therapies to
      assist with the management of their pain and other cancer-related symptoms. The
      World Health Organization's suggested approach to pain management begins with the
      use of time honored opioids, but recommends the use of adjuvant therapies early
      in the management process. Complementary and alternative therapies are being used
      by more patients each year to assist with the management of their pain.
      Practitioners and researchers must be aware of the evidence that exists to
      support or refute the use of these therapies. In this manuscript we review
      evidence from the recent past on complementary and alternative therapies for pain
      with emphasis on more common modalities including acupuncture, bio-energy,
      massage, and music.

PMID- 22639185
TI  - Nanobubbles are not a superficial matter.

PMID- 22639182
TI  - Comorbidity in perimenstrual migraine.
AB  - Comorbidity may be defined as the association of two or more diseases in
      individuals at a frequency greater than that expected statistically by chance.
      Studying the co-occurrence of two disorders requires a careful statistical
      analysis before any clear conclusion on causality is reached. Many studies have
      looked for an association between migraine and many diseases, reporting several
      sometimes controversial comorbidities in migraine subjects. Although migraine is
      more common in women than in men, very few studies have analyzed the comorbidity
      of perimenstrual migraine, a migraine sub-type characterized by attacks of
      migraine without aura related to menstruation. We review the studies on migraine
      comorbidities, particularly migraine without aura in women.

PMID- 22639187
TI  - Duplex criteria for in-stent restenosis in the superficial femoral artery.
AB  - OBJECTIVES: To elucidate the optimal cutoff and accuracy of duplex
      ultrasonography (DUS) parameters for in-stent restenosis (ISR) after nitinol
      stenting in the superficial femoral artery (SFA). BACKGROUND: Few data are
      available regarding the performance of DUS for binary ISR based on quantitative
      vessel analysis (QVA) in the era of SFA nitinol stenting. METHODS: This
      retrospective study included 74 in-stent stenoses of SFA who underwent DUS before
      follow-up angiography. DUS parameters, such as peak systolic velocity (PSV) and
      the peak systolic velocity ratio (PSVR), were compared with percent diameter
      stenosis (%DS) from a QVA basis. RESULTS: There was a statistically significant
      correlation (P < 0.001) between "%DS and PSV" and "%DS and PSVR," and the
      correlation with %DS proved to be stronger in PSVR (R = 0.720) than in PSV (R =
      0.672). The best performing parameter for ISR (50% or greater stenosis) was
      revealed PSVR, as the areas under the receiver operator characteristics curves
      using PSVR and PSV were 0.908 and 0.832, respectively. A PSVR cut off value of
      2.85 yielded the best predictive value with sensitivity of 88%, specificity of
      84%, and accuracy of 86%. The positive predictive value was 85% and the negative
      predictive value was 88%. CONCLUSIONS: A PSVR of 2.85 is the optimal threshold
      for ISR after nitinol stenting in the SFA. Further large prospective studies are
      required for the validation and establishment of uniform criteria for DUS
      parameters.

PMID- 22639188
TI  - Iron deficiency on neuronal function.
AB  - Because of the intrinsic ability of iron to catalyze the formation of reactive
      oxygen species, it has been associated with oxidative stress and
      neurodegenerative diseases. However, iron deficiency (ID) also negatively impacts
      various functions of the brain, suggesting that iron plays an important
      physiological role in neuronal processes such as myelination, synaptogenesis,
      behavior and synaptic plasticity (SP). ID not only produces changes in the
      hippocampus, striatum, amygdale or prefrontal cortex, it also affects the
      interaction among these systems. In both humans and rodents, the perturbations of
      these structures are associated to cognitive deficits. These cognitive
      alterations have been well correlated with changes in neural plasticity, the
      possible cellular substrate of memory and learning. Given that SP is strongly
      affected by early ID and the lasting-neurological consequences remain even after
      ID has been corrected, it is important to prevent ID as well as to seek effective
      therapeutic interventions that reduce or reverse the long-term effects of the ID
      in the nervous system. This review will give an overview of the literature on the
      effects of iron deficit in neuronal functions such as behavior, neurotransmission
      and SP. We also discuss our recent data about the possible oxidative effect of
      iron on the mechanisms involved in neural plasticity.

PMID- 22639189
TI  - Mercury toxicity, molecular response and tolerance in higher plants.
AB  - Mercury (Hg) contamination in soils has become a great concern as a result of its
      natural release and anthropogenic activities. This review presents broad aspects
      of our recent understanding of mercury contamination and toxicology in plants
      including source of Hg contamination, toxicology, tolerant regulation in plants,
      and minimization strategy. We first introduced the sources of mercury
      contamination in soils. Mercury exists in different forms, but ionic mercury
      (Hg(2+)) is the predominant form in soils and readily absorbed by plants. The
      second issue to be discussed is the uptake, transport, and localization of Hg(2+)
      in plants. Mercury accumulated in plants evokes severe phytotoxicity and impairs
      numerous metabolic processes including nutrient uptake, water status, and
      photosynthesis. The mechanisms of mercury-induced toxicology, molecular response
      and gene networks for regulating plant tolerance will be reviewed. In the case of
      Hg recent much progress has been made in profiling of transcriptome and more
      importantly, uncovering a group of small RNAs that potentially mediates plant
      tolerance to Hg. Several newly discovered signaling molecules such as nitric
      oxide and carbon monoxide have now been described as regulators of plant
      tolerance to Hg. A recently emerged strategy, namely selection and breeding of
      plant cultivars to minimize Hg (or other metals) accumulation will be discussed
      in the last part of the review.

PMID- 22639190
TI  - Evolution and dispersal of emmer wheat (Triticum sp.) from novel haplotypes of
      Ppd-1 (photoperiod response) genes and their surrounding DNA sequences.
AB  - The sequence data from 5' UTR, intronic, coding and 3' UTR regions of Ppd-A1 and
      Ppd-B1 were investigated for a total of 158 accessions of emmer wheat landraces
      comprising 19 of wild emmer wheat (Triticum dicoccoides), 45 of hulled emmer
      wheat (T. dicoccum) and 94 of free-threshing (FT) emmer wheat (T. durum etc.). We
      detected some novel types of deletions in the coding regions from 22 hulled emmer
      accessions and 20 FT emmer accessions. Emmer wheat accessions with these
      deletions could produce predicted proteins likely to lack function. We also
      observed some novel mutations in Ppd-B1. Sixty-seven and forty-one haplotypes
      were found in Ppd-A1 and Ppd-B1, respectively. Some mutations found in this study
      have not been known, so they have potential for useful genetic resources for
      wheat breeding. On the basis of sequence data from the 5' UTR region, both Ppd-A1
      and Ppd-B1 haplotypes were divided into two groups (Type AI/AII and Type BI/BII).
      Types AI and AII of Ppd-A1 suggested gene flow between wild and hulled emmer. On
      the other hand, Types BI and BII of Ppd-B1 suggested gene flow between wild and
      FT emmer. More than half of hulled emmer accessions were Type AII/BI but few FT
      emmer accessions were of this type. Therefore, over half of the hulled emmer did
      not contribute to evolution of FT emmer.

PMID- 22639191
TI  - Stature and body mass estimation from skeletal remains in the European Holocene.
AB  - Techniques that are currently available for estimating stature and body mass from
      European skeletal remains are all subject to various limitations. Here, we
      develop new prediction equations based on large skeletal samples representing
      much of the continent and temporal periods ranging from the Mesolithic to the
      20th century. Anatomical reconstruction of stature is carried out for 501
      individuals, and body mass is calculated from estimated stature and biiliac
      breadth in 1,145 individuals. These data are used to derive stature estimation
      formulae based on long bone lengths and body mass estimation formulae based on
      femoral head breadth. Prediction accuracy is superior to that of previously
      available methods. No systematic geographic or temporal variation in prediction
      errors is apparent, except in tibial estimation of stature, where northern and
      southern European formulae are necessary because of the presence of relatively
      longer tibiae in southern samples. Thus, these equations should bebroadly
      applicable to European Holocene skeletal samples.

PMID- 22639192
TI  - The effect of alcohol structures on the interaction mode with the hexameric
      capsule of resorcin[4]arene.
AB  - After more than a century of research on resorcin[4]arenes (1) it is clear that
      such systems form spontaneously [1(6)(H(2)O)(8)]-type hexameric capsules in wet,
      non-polar, organic solvents. However, the interactions of these hexameric
      capsules with alcohols are far from being solved. Here we provide the results of
      an extensive study on the interaction of different alcohols with the hexameric
      capsules of resorcin[4]arene 1a by focusing on the exchange of magnetization
      manifested in diffusion NMR measurements of such capsular systems. We found that
      some alcohols such as 2-octyl-1-dodecanol and 1-octadecanol do not interact with
      the hexamers of 1a, whereas other alcohols such as 3-ethyl-3-pentanol, 2-ethyl-1
      butanol and more act as simple guests and are simply encapsulated in the
      hexamers. Others alcohols such as 3-pentanol, 2-methyl-1-butanol and others, are
      part of the hexameric structure where they can exchange magnetization with
      alcohols in the bulk. The bulkier alcohols, due to an increase of the chain
      length or in branching, have a higher tendency to be encapsulated rather than
      being part of the hexameric capsule superstructure. This study demonstrate the
      unique information that diffusion NMR spectroscopy can provide on supramolecular
      systems in solution and on the precaution that should be exercised when analyzing
      diffusion NMR data of such dynamic supramolecular capsules.

PMID- 22639193
TI  - The development of FtsZ inhibitors as potential antibacterial agents.
AB  - The emergence and prevalence of bacterial resistance has resulted in a clear
      demand for novel antibacterial drugs. As a tubulin homologue, FtsZ is an
      essential cell-division protein in prokaryotic organisms and is showing
      increasing promise as a target for antibacterial drug discovery. This review
      describes the role of FtsZ in bacterial cytokinesis and various FtsZ inhibitors,
      with particular focus on their discovery, antibacterial activities, mechanisms of
      action, synthetic methods, and representative analogues.

PMID- 22639194
TI  - Measuring bioconcentration factors in fish using exposure to multiple chemicals
      and internal benchmarking to correct for growth dilution.
AB  - Modern chemical legislation requires measuring the bioconcentration factor (BCF)
      of large numbers of chemicals in fish. The BCF must be corrected for growth
      dilution, because fish growth rates vary between laboratories. Two hypotheses
      were tested: (1) that BCFs of multiple chemicals can be measured simultaneously
      in one experiment, and (2) that internal benchmarking using a conservative test
      substance in the chemical mixture can be used to correct for growth dilution.
      Bioconcentration experiments were conducted following major elements of the OECD
      305 guideline. Fish were simultaneously exposed to 11 chemicals selected to cover
      a range of BCFs and susceptibility to biotransformation. A method was developed
      to calculate the growth-corrected elimination rate constant from the
      concentration ratio of the analyte and a benchmarking chemical for which growth
      dilution dominated other elimination mechanisms. This method was applied to the
      experimental data using hexachlorobenzene as the benchmarking chemical. The
      growth dilution correction lowered the apparent elimination rate constants by
      between 5% and a factor of four for eight chemicals, while for two chemicals the
      growth-corrected elimination rate constant was not significantly different from
      zero. The benchmarking method reduced the uncertainty in the elimination rate
      constant compared to the existing method for growth dilution correction. The BCFs
      from exposing fish to 10 chemicals at once were consistent with BCF values from
      single-chemical exposures from the literature, supporting hypothesis 1.

PMID- 22639195
TI  - A large geometric distortion in the first photointermediate of rhodopsin,
      determined by double-quantum solid-state NMR.
AB  - Double-quantum magic-angle-spinning NMR experiments were performed on 11,12
      (13)C(2)-retinylidene-rhodopsin under illumination at low temperature, in order
      to characterize torsional angle changes at the C11-C12 photoisomerization site.
      The sample was illuminated in the NMR rotor at low temperature (~120 K) in order
      to trap the primary photointermediate, bathorhodopsin. The NMR data are
      consistent with a strong torsional twist of the HCCH moiety at the isomerization
      site. Although the HCCH torsional twist was determined to be at least 40 degrees
      , it was not possible to quantify it more closely. The presence of a strong twist
      is in agreement with previous Raman observations. The energetic implications of
      this geometric distortion are discussed.

PMID- 22639196
TI  - MaxOcc: a web portal for maximum occurrence analysis.
AB  - The MaxOcc web portal is presented for the characterization of the conformational
      heterogeneity of two-domain proteins, through the calculation of the Maximum
      Occurrence that each protein conformation can have in agreement with experimental
      data. Whatever the real ensemble of conformations sampled by a protein, the
      weight of any conformation cannot exceed the calculated corresponding Maximum
      Occurrence value. The present portal allows users to compute these values using
      any combination of restraints like pseudocontact shifts, paramagnetism-based
      residual dipolar couplings, paramagnetic relaxation enhancements and small angle
      X-ray scattering profiles, given the 3D structure of the two domains as input.
      MaxOcc is embedded within the NMR grid services of the WeNMR project and is
      available via the WeNMR gateway at http://py
      enmr.cerm.unifi.it/access/index/maxocc . It can be used freely upon registration
      to the grid with a digital certificate.

PMID- 22639197
TI  - Outpatient treatment in German adolescents with depression: an analysis of
      nationwide health insurance data.
AB  - PURPOSE: Data on medical treatment of adolescents with depression are scarce.
      This study aimed to examine outpatient health services utilisation of depressive
      disorders in adolescents. METHODS: Data of a statutory health insurance company
      were analysed and outpatients from 12 to 18 years old with diagnosed depression
      during a 1-year period (2009) were identified. For this cohort, the prescription
      of antidepressants and psychotherapy was evaluated with respect to age and sex.
      RESULTS: A total of 4295 patients (41.2% males; mean age, 15.5 years) matched the
      inclusion criteria. Of the patients, 29.7% consulted a child and adolescent
      psychiatrist. A total of 59.6% were treated with psychotherapy only, 9.6% were
      treated with a combination of psychotherapy and antidepressants, and 1.9%
      received only antidepressants. For 28.8% of patients, no specific depression
      related treatment was prescribed. A total of 1357 packages of antidepressants
      were analysed, of which fluoxetine (24.4% of prescriptions), citalopram (14.0%),
      and mirtazapine (9.7%) were the most frequently prescribed substances. Regarding
      substance classes, selective serotonin reuptake inhibitors (SSRIs; 55.6%),
      tricyclic antidepressants (TCAs; 17.9%), and hypericum (St. John's wort; 8.5%)
      were most common. CONCLUSIONS: Although the underlying data were coded for
      insurance purposes, which might result in some data impreciseness, this
      naturalistic study furnishes evidence that outpatient treatment of adolescents
      with depressive disorders in Germany only partly complies with guideline
      recommendations for first-line treatment: Although the prescriptions of SSRI for
      adolescent depression have risen over recent years, still, a quarter of
      antidepressant prescriptions for adolescents with depression were TCA or
      hypericum. Therefore, dissemination of knowledge on state-of-the-art treatment
      for adolescent depression remains a major educational goal.

PMID- 22639198
TI  - Lower lip reconstruction with Abbe-Estlander flap modification: preserving the
      same side vascular pedicle.

PMID- 22639199
TI  - Anatomical study and modified incision of the infrahyoid myocutaneous flap.
AB  - Skin paddle necrosis and neck function damage, particularly rotation, are two
      problems associated with the infrahyoid myocutaneous flap clinical application.
      The aim of this study was to investigate vessel supply and drainage of the skin
      paddle and to report our modified flap incision technique. In this work, we
      conducted a cadaveric study and reviewed our experience with the modified
      incision and describe the surgical procedure. We confirmed the platysma muscle
      branch feeds the skin paddle overlying the infrahyoid myocutaneous flap. The
      length between the platysma muscle branch entry point and its originating point
      measured 3.38 (min 2.51, max 4.52) cm. The flap has two drainage systems. The
      skin paddle of the flap was drained by the anterior jugular vein and external
      jugular vein, respectively, or both. The infrahyoid muscles were drained by the
      superior thyroid vein. In the early four cases, where the platysma muscle branch
      was not protected, skin paddle necrosis appeared in two cases. In the later seven
      cases, which involved preservation of the platysma muscle branch, all flaps
      successfully survived. Patients in whom a modified incision was used all achieved
      both satisfactory rehabilitation of neck function and an adequate esthetic
      result. We conclude that the necrosis rate of the skin paddle of the flap can be
      reduced by carefully protecting its supply and drainage vessels. The modified
      incision can improve neck function postoperatively.

PMID- 22639200
TI  - Cartilaginous myringoplasty: the endoscopic transcanal procedure.
AB  - The objectives of the study are to evaluate the feasibility, results and
      complications of the endoscopic transcanal cartilaginous myringoplasty. Thirty
      patients with a tympanic membrane perforation underwent a transcanal endoscopic
      cartilaginous myringoplasty, between June 2008 and January 2010. Three patients
      had a residual perforation at 2 months after surgery. At 1 year, the perforation
      was closed for 29 patients (96 %). There was no case of blunting, lateralization
      of the tympanic membrane or ossicular injury. Two patients had an iatrogenic
      superficial cholesteatoma in the tympanic membrane. There was no significant
      postoperative worsening of sensorineural hearing loss. The preoperative Air Bone
      Gap (ABG) was not correlated with the size or site of TMP. The evolution of ABG
      postoperatively was not significant. The statistical analysis was performed by
      the Student's t test. The endoscopic transcanal cartilaginous myringoplasty is a
      minimally invasive, effective and reliable procedure in the management of the
      tympanic membrane perforations.

PMID- 22639201
TI  - Flexible bronchoscopy as a valuable tool in the evaluation of infants with
      stridor.
AB  - The aim is to determine clinical characteristics, flexible bronchoscopy (FB)
      findings including associated airway abnormalities and other conditions,
      treatment modalities and long term follow-up of children with congenital stridor.
      Medical records of children, who underwent FB for the evaluation of stridor
      between 1 January 2004 and 31 December 2009 were retrospectively reviewed.
      Demographic characteristics, symptoms and physical examination findings at
      presentation, FB findings, follow-up data including the time to resolution of
      symptoms and treatment modalities, presence of associated conditions were
      assessed. 109 children were enrolled to the study. Laryngomalacia was the most
      common etiology for stridor. Laryngomalacia was isolated in 37 patients and 54
      patients had secondary airway lesions (SALs). Diagnoses other than laryngomalacia
      such as subglottic hemangioma, subglottic web, isolated tracheomalacia were found
      in 18 patients. In 90 % of patients, stridor resolved before 3 years of age
      without any surgical intervention and there was no significant difference in
      terms of the persistence of stridor between patients with isolated laryngomalacia
      and associated SALs. Duration of stridor was significantly longer in both
      patients with neurological abnormalities and reflux symptoms. Surgical procedure
      was performed in 19 of the patients. There is a high incidence of SALs in
      patients with laryngomalacia. FB is helpful for identifying anomalies requiring
      surgical treatment.

PMID- 22639202
TI  - Enchondroma with secondary aneurysmal bone cyst.
AB  - An enchondroma with complex cystic changes of the proximal femur is described in
      a 13-year-old male. The case illustrates a unique presentation of an enchondroma
      and reinforces the importance of considering the presence of secondary aneurysmal
      bone cysts in both benign and malignant lesions of bone.

PMID- 22639203
TI  - Ossicles of lumbar articular facets: normal variant or spondylolytic variant?
AB  - PURPOSE: The objective of this study was to establish the prevalence and
      significance of ossicles of lumbar articular facets (OLAF) in young athletes with
      backache diagnosed by multi-detector computed tomography (MDCT). MATERIALS AND
      METHODS: The MDCT examinations of the lumbar spine carried out for suspected
      spondylolysis on 46 consecutive symptomatic young athletes presenting to a sports
      injury clinic over a 1-year period were retrospectively reviewed. OLAF study
      included detailed correlation with the structural and morphological stress
      features of the posterior neural arches. This was then compared with a control
      group composed of 39 patients. RESULTS: Twenty-three OLAF were identified in 15
      patients. Eleven of the 15 patients with ossicles had posterior element stress
      changes (PEST)/pars defects. In the control group, two OLAF were identified in
      two patients, one demonstrating PEST changes. CONCLUSION: The high prevalence of
      OLAF in young symptomatic athletes compared with the asymptomatic control group
      is indicative of stress fractures. The non-united articular process fractures
      should be regarded as part of the spectrum of stress-induced changes in the
      posterior neural arch in the same way as spondylolysis. MDCT with volumetric
      acquisition and multi-planar reformation is the most reliable investigation in
      the diagnosis of OLAF. KEY POINTS: 1) This CT study supports a traumatic
      aetiology for lumbar articular facets ossicles. 2) OLAF represent part of a
      spectrum of stress-induced changes in the posterior neural arch. 3) OLAF are
      associated with typical spondylolysis. 4) OLAF can be overlooked on reverse
      gantry angle computed tomography (RG-CT). 5) OLAF may account for some of the
      discrepancy between radionuclide and RG-CT studies.

PMID- 22639205
TI  - Anaphylaxis at image-guided epidural pain block secondary to corticosteroid
      compound.
AB  - Anaphylaxis during image-guided interventional procedures is a rare but
      potentially fatal event. Anaphylaxis to iodinated contrast is an established and
      well-recognized adverse effect. However, anaphylaxis to some of the other
      frequently administered medications given during interventional procedures, such
      as corticosteroids, is not common knowledge. During caudal epidural injection,
      iodinated contrast is used to confirm needle placement in the epidural space at
      the level of the sacral hiatus. A combination of corticosteroid, local
      anesthetic, and saline is subsequently injected. We describe a very rare case of
      anaphylaxis to a component of the steroid medication instilled in the caudal
      epidural space.

PMID- 22639204
TI  - Calculating anterior glenoid bone loss using the Bernageau profile view.
AB  - OBJECTIVE: To determine if it is possible to measure glenoid bone loss by using
      the Bernageau view and to compare it to a 3D CT scan. MATERIALS AND METHODS:
      Fifty healthy subjects with a mean age of 34 +/- 8 years old and 31 (62 %) male
      were submitted to the Bernageau view X-ray of both shoulders. Three blinded
      evaluators measured the distance between the posterior and anterior glenoid rim.
      Ten patients with multiple episodes of unilateral traumatic anterior shoulder
      dislocation with a mean age of 34 +/- 9.1 years old and 90 % male were submitted
      to the same X-ray technique to determine the percentage of glenoid bone loss.
      They were also submitted to a bilateral 3D CT scan to be compared to the
      radiographs. RESULTS: In the 50 asymptomatic subjects, the AP distance was 24.48
      mm +/- 3.32 mm in the left shoulder and 24.82 mm +/- 3.16 mm in the right
      shoulder. Comparing the X-ray study and the 3D CT scan of the ten patients with
      multiple episodes, there was no significant statistical difference of the AP
      normal distance in both methods (p = 0.646), the AP erosion distance (p = 0.386),
      as well as the percentage of bone loss (p = 0.513). Moreover, the differences
      between the percentages of bone loss in the X-ray, compared with the 3D CT scan
      were, on average 2.28 % (range 0 to 6.05 %). CONCLUSIONS: The Bernageau
      radiographic view is an accurate and reproducible technique for measuring the
      presence of glenoid erosion, with similar results when compared to the 3D CT
      scan.

PMID- 22639206
TI  - Multidirectional instability of the shoulder: rotator interval dimension and
      capsular laxity evaluation using MR arthrography.
AB  - OBJECTIVES: To compare the rotator interval and capsular dimension as measured on
      MR arthrography between patients with clinically diagnosed multidirectional
      instability (MDI) and control subjects with no instability. MATERIALS AND
      METHODS: We retrospectively reviewed a consecutive series of 658 shoulders that
      had undergone MR arthrography between 2006 and 2010. Of these, 97 shoulders were
      included in the present study. These shoulders were divided into two groups
      according to the clinically established diagnoses. The MDI group comprised 47
      shoulders with atraumatic multidirectional shoulder instability, and the control
      group comprised 50 shoulders with no instability. Two independent observers
      measured the width and depth of the rotator interval, and the capsular dimensions
      at the anterior, anteroinferior, inferior, posteroinferior, and posterior regions
      in the two groups using MR arthrography. RESULTS: The rotator interval width and
      depth were significantly greater in the MDI group (width, observer 1, 17.7 mm,
      observer 2, 17.9 mm; depth, observer 1, 8.9 mm, observer 2, 8.8 mm) than in the
      control group (width, observer 1, 14.3 mm, observer 2, 14.5 mm; depth, observer
      1, 5.9 mm, observer 2, 6.2 mm) (p < .001). The capsular dimensions at the
      inferior and posteroinferior regions were significantly larger in the MDI group
      (inferior, observer 1, 27.9 mm, observer 2, 27.8 mm; posteroinferior, observer 1,
      27.0 mm, observer 2, 27.1 mm) than in the control group (inferior, observer 1,
      25.7 mm, observer 2, 25.3 mm; posteroinferior, observer 1, 23.3 mm, observer 2,
      23.6 mm) (p < .05). A width greater than 15.2 mm or a depth greater than 6.4 mm
      of the rotator interval, suggesting MDI, had sensitivities of 81 and 92 % for
      observer 1, and 79 and 94 % for observer 2, and specificities of 66 and 72 % for
      observer 1, and 62 and 66 % for observer 2, respectively. CONCLUSIONS:
      Measurements of the rotator interval and the size of the distended inferior and
      posteroinferior joint capsule on MR arthrography are greater in shoulders with
      clinical MDI than in stable shoulders.

PMID- 22639207
TI  - Metaphyseal chondromatosis combined with D-2-hydroxyglutaric aciduria in four
      patients.
AB  - We report four patients who presented with a severe form of metaphyseal
      chondromatosis in association with D-2-hydroxyglutaric aciduria (D-2-HGA). All
      patients showed splaying columns of irregular ossification defects with bulbous
      metaphyses of the long tubular bones, as well as remarkable involvement of the
      short tubular and flat bones. The vertebral bodies revealed platyspondyly with
      irregular, stippled endplates. D-2-HGA has been described as a neurometabolic
      disorder manifesting a broad range of impairment in mental and motor development.
      Although hydroxyglutaric acid was excreted in high amounts in the urine of all
      four patients described herein, no significant neurologic abnormalities were
      evident. This unusual combination of characteristic skeletal and metabolic
      abnormalities has rarely been reported. Thus, our report will facilitate the
      recognition of this distinctive entity, and we suggest that a urine organic acid
      screening be obtained in patients who present with generalized enchondromatosis.

PMID- 22639208
TI  - Flow cytometry in environmental microbiology: a rapid approach for the isolation
      of single cells for advanced molecular biology analysis.
AB  - The isolation and subsequent characterization of microbial cells from within
      environmental samples is a difficult process. Flow cytometry and cell sorting,
      when combined with the application of fluorescent probes, have the capability for
      the detection and separation of diverse microbial populations from within complex
      mixtures. The isolation of single cells allows for downstream investigations
      towards system-level characterization of unknown Bacterial Phyla to occur. We
      describe here the combination of fluorescent in situ hybridization and cell
      sorting for the detection and isolation of Candidate Division TM7 bacteria from
      an enriched soil sample. The result is the isolation of rare cells suitable for
      advanced molecular analysis including whole genome amplification and high
      throughput pyrosequencing.

PMID- 22639209
TI  - Pressure cycling technology in systems biology.
AB  - Systems biologists frequently seek to integrate complex data sets of diverse
      analytes into a comprehensive picture of an organism's biological state under
      defined environmental conditions. Although one would prefer to collect these data
      from the same sample, technical limitations with traditional sample preparation
      methods often commit the investigator to extracting one type of analyte at the
      expense of losing all others. Often, volume further constrains the range of
      experiments that can be collected from a single sample. The practical solution
      employed to date has been to rely on information collected from multiple
      replicate experiments and similar historical or reported data. While this
      approach has been popular, the integration of information collected from
      disparate single-analyte sample preparation streams increases uncertainty due to
      nonalignment during comparative analysis, and such gaps accumulate quickly when
      combining multiple data sets. Regrettably, discontinuities between separate data
      streams can confound a whole understanding of the biological system being
      investigated. This difficulty is further compounded for researchers handling
      highly pathogenic samples, in which it is often necessary to use harsh chemicals
      or high-energy sterilization procedures that damage the target analytes. Ultra
      high pressure cycling technology (PCT), also known as barocycling, is an emerging
      sample preparation strategy that has distinct advantages for systems biology
      studies because it neither commits the researcher to pursuing a specific analyte
      nor leads to the degradation of target material. In fact, samples prepared under
      pressure cycling conditions have been shown to yield a more complete set of
      analytes due to uniform disruption of the sample matrix coupled with an
      advantageous high pressure solvent environment. Fortunately, PCT safely
      sterilizes and extracts complex or pathogenic viral, bacterial, and spore samples
      without adversely affecting the constituent biomolecules valued as informative
      and meaningful analytes. This chapter provides procedures and findings associated
      with incorporating PCT into systems biology as a new and enabling approach to
      preanalytical sample treatment.

PMID- 22639210
TI  - Targeted isolation of proteins from natural microbial communities living in an
      extreme environment.
AB  - Microorganisms from extreme environments are often very difficult to cultivate,
      precluding detailed study by biochemical and physiological techniques. Recent
      advances in genomic sequencing and proteomic measurements of samples obtained
      from natural communities have allowed new access to these uncultivated
      extremophiles and identified abundant proteins that can be isolated directly from
      natural samples. Here we report the isolation of two abundant heme proteins from
      low-diversity biofilm microbial communities that thrive in very acidic (pH ~ 1),
      metal-rich water in a subsurface mine. Purification and detailed characterization
      of these proteins has afforded new insight into the possible mechanism of Fe(II)
      oxidation by Leptospirillum Group II, the dominant population in most of these
      biofilms, and demonstrated that the abundance and posttranslational modifications
      of one of these proteins is dependent on the lifecycle of the biofilm.

PMID- 22639211
TI  - Bacterial identification and subtyping using DNA microarray and DNA sequencing.
AB  - The era of fast and accurate discovery of biological sequence motifs in
      prokaryotic and eukaryotic cells is here. The co-evolution of direct genome
      sequencing and DNA microarray strategies not only will identify, isotype, and
      serotype pathogenic bacteria, but also it will aid in the discovery of new gene
      functions by detecting gene expressions in different diseases and environmental
      conditions. Microarray bacterial identification has made great advances in
      working with pure and mixed bacterial samples. The technological advances have
      moved beyond bacterial gene expression to include bacterial identification and
      isotyping. Application of new tools such as mid-infrared chemical imaging
      improves detection of hybridization in DNA microarrays. The research in this
      field is promising and future work will reveal the potential of infrared
      technology in bacterial identification. On the other hand, DNA sequencing by
      using 454 pyrosequencing is so cost effective that the promise of $1,000 per
      bacterial genome sequence is becoming a reality. Pyrosequencing technology is a
      simple to use technique that can produce accurate and quantitative analysis of
      DNA sequences with a great speed. The deposition of massive amounts of bacterial
      genomic information in databanks is creating fingerprint phylogenetic analysis
      that will ultimately replace several technologies such as Pulsed Field Gel
      Electrophoresis. In this chapter, we will review (1) the use of DNA microarray
      using fluorescence and infrared imaging detection for identification of
      pathogenic bacteria, and (2) use of pyrosequencing in DNA cluster analysis to
      fingerprint bacterial phylogenetic trees.

PMID- 22639212
TI  - Genetic manipulation of the obligate chemolithoautotrophic bacterium Thiobacillus
      denitrificans.
AB  - Chemolithoautotrophic bacteria can be of industrial and environmental importance,
      but they present a challenge for systems biology studies, as their central
      metabolism deviates from that of model organisms and there is a much less
      extensive experimental basis for their gene annotation than for typical
      organoheterotrophs. For microbes with sequenced genomes but unconventional
      metabolism, the ability to create knockout mutations can be a powerful tool for
      functional genomics and thereby render an organism more amenable to systems
      biology approaches. In this chapter, we describe a genetic system for
      Thiobacillus denitrificans, with which insertion mutations can be introduced by
      homologous recombination and complemented in trans. Insertion mutations are
      generated by in vitro transposition, the mutated genes are amplified by the PCR,
      and the amplicons are introduced into T. denitrificans by electroporation. Use of
      a complementation vector, pTL2, based on the IncP plasmid pRR10 is also
      addressed.

PMID- 22639213
TI  - Genome-wide mapping of the binding sites of proteins that interact with DNA.
AB  - The coordinated regulation of the expression of a group of genes by a specific
      transcription factor frequently lies at the heart of the ability of a bacterium
      to respond to an environmental signal, or to progress through a developmental
      program. Thus, in many situations, it is of interest to identify all of the genes
      that are under the control of a particular regulatory protein. This chapter
      begins with a brief overview of some of the methods that have been used in
      attempts to identify some or all of the members of a regulon (i.e., those genes
      that are the targets for a transcriptional activator or repressor). Thereafter,
      the chapter will focus on one technique, chromatin immunoprecipitation and
      microarray analysis (ChIP-chip) and some of its variants. Design considerations
      and some protocols for ChIP-chip experiments are provided, along with some
      considerations related to downstream data analysis. ChIP-chip is a method for the
      genome-wide localization of protein-binding sites. In a typical ChIP-chip
      protocol, proteins are cross-linked nonspecifically to DNA in vivo. Chromatin is
      extracted and sheared, and specific protein-DNA complexes are immunoprecipitated
      with a suitable antibody. After purification, the DNA is hybridized to a
      microarray (after an amplification step in some protocols), together with a
      differentially labeled reference sample. Features on the microarray that show an
      elevated fluorescence ratio reveal DNA sequences that were enriched by
      immunoprecipitation. The corresponding genomic locations are those that were
      enriched, and are therefore close to sites of binding. The use of high-density
      tiled microarrays allows for binding site localization with quite high
      resolution. It is likely that ChIP-chip will soon be superseded by ChIP-seq, in
      which the immunoprecipitated DNA is analyzed directly by next-generation
      sequencing technologies. ChIP-chip and ChIP-seq applications are not confined to
      regulatory proteins, since they can be used with any protein that binds to DNA,
      either directly, or indirectly via an interaction with another protein. Thus,
      ChIP-chip has been used successfully to map binding sites for nucleoid proteins,
      and proteins involved in DNA replication.

PMID- 22639214
TI  - Microbial proteomics using mass spectrometry.
AB  - Proteomic analyses involve a series of intricate, interdependent steps involving
      approaches and technical issues that must be fully coordinated to obtain the
      optimal amount of required information about the test subject. Fortunately, many
      of these steps are common to most test subjects, requiring only modifications to
      or, in some cases, substitution of some of the steps to ensure they are relevant
      to the desired objective of a study. This fortunate occurrence creates an
      essential core of proteomic approaches and techniques that are consistently
      available for most studies, regardless of test subject. In this chapter, an
      overview of some of these core approaches, techniques, and mass spectrometric
      instrumentation is given, while indicating how such steps are useful for and
      applied to bacterial investigations. To exemplify how such proteomic concepts and
      techniques are applicable to bacterial investigations, a practical, quantitative
      method useful for bacterial proteomic analysis is presented with a discussion of
      possibilities, pitfalls, and some emerging technology to provide a compilation of
      information from the diverse literature that is intermingled with experimental
      experience.

PMID- 22639215
TI  - Fourier transform infrared spectroscopy for molecular analysis of microbial
      cells.
AB  - A rapid and inexpensive method to characterise chemical cell properties and
      identify the functional groups present in the cell wall is Fourier transform
      infrared spectroscopy (FTIR). Infrared spectroscopy is a well-established
      technique to identify functional groups in organic molecules based on their
      vibration modes at different infrared wave numbers. The presence or absence of
      functional groups, their protonation states, or any changes due to new
      interactions can be monitored by analysing the position and intensity of the
      different infrared absorption bands. Additionally, infrared spectroscopy is non
      destructive and can be used to monitor the chemistry of living cells. Despite the
      complexity of the spectra, the elucidation of functional groups on Gram-negative
      and Gram-positive bacteria has been already well documented in the literature.
      Recent advances in detector sensitivity have allowed the use of micro-FTIR
      spectroscopy as an important analytical tool to analyse biofilm samples without
      the need of previous treatment. Using FTIR spectroscopy, the infrared bands
      corresponding to proteins, lipids, polysaccharides, polyphosphate groups, and
      other carbohydrate functional groups on the bacterial cells can now be identified
      and compared along different conditions. Despite some differences in FTIR spectra
      among bacterial strains, experimental conditions, or changes in microbiological
      parameters, the IR absorption bands between approximately 4,000 and 400 cm(-1)
      are mainly due to fundamental vibrational modes and can often be assigned to the
      same particular functional groups. In this chapter, an overview covering the
      different sample preparation protocols for infrared analysis of bacterial cells
      is given, alongside the basic principles of the technique, the procedures for
      calculating vibrational frequencies based on simple harmonic motion, and the
      advantages and disadvantages of FTIR spectroscopy for the analysis of
      microorganisms.

PMID- 22639216
TI  - Mass spectrometry-based microbial metabolomics.
AB  - Through the characterization of metabolic pathways, metabolomics is able to
      illuminate the activities of a cell at the functional level. However, the
      metabolome, which is comprised of hundreds of chemically diverse metabolites, is
      rather difficult to monitor. Mass spectrometry (MS)-based profiling methods are
      increasingly being utilized for this purpose. To this end, MS is often coupled to
      the separation techniques gas chromatography (GC), liquid chromatography (LC),
      and capillary electrophoresis (CE). The mass-based selectivity that the MS
      provides, together with the chromatographic or electrophoretic separation of
      analytes, creates hyphenated techniques that are ideally suited to the
      measurement of large numbers of metabolites from microbial extracts. In this
      chapter, we describe GC-MS, LC-MS, and CE-MS methods that are applicable to
      microbial metabolomics experiments.

PMID- 22639217
TI  - Fast sampling of the cellular metabolome.
AB  - Obtaining meaningful snapshots of the metabolome of microorganisms requires rapid
      sampling and immediate quenching of all metabolic activity, to prevent any
      changes in metabolite levels after sampling. Furthermore, a suitable extraction
      method is required ensuring complete extraction of metabolites from the cells and
      inactivation of enzymatic activity, with minimal degradation of labile compounds.
      Finally a sensitive, high-throughput analysis platform is needed to quantify a
      large number of metabolites in a small amount of sample. An issue which has often
      been overlooked in microbial metabolomics is the fact that many intracellular
      metabolites are also present in significant amounts outside the cells, and may
      interfere with the endometabolome measurements. Attempts to remove the
      extracellular metabolites with dedicated quenching methods often induce release
      of intracellular metabolites into the quenching solution. For eukaryotic
      microorganisms, leakage can be minimized by adaptation of the quenching method.
      For prokaryotic cells this had not yet been accomplished, so the application of a
      differential method whereby metabolites are measured in the culture supernatant
      as well as in total broth samples, to calculate the intracellular levels by
      subtraction, seems to be the most suitable approach. Here we present an overview
      of different sampling, quenching, and extraction methods developed for microbial
      metabolomics, described in the literature. Detailed protocols are provided for
      rapid sampling, quenching, and extraction for measurement of metabolites in total
      broth samples, washed cell samples and supernatant, to be applied for
      quantitative metabolomics of both eukaryotic and prokaryotic microorganisms.

PMID- 22639218
TI  - Metabolic pathway determination and flux analysis in nonmodel microorganisms
      through 13C-isotope labeling.
AB  - C-isotope labeling is a commonly used technique for determining and quantifying
      pathways in microorganisms under various growth conditions. The experimental
      protocol consists of feeding the cell with a composition-defined substrate and
      measuring isotopic labeling patterns in the synthesized metabolites (often the
      amino acids). Not only can the labeling information be cross-referenced with
      genomic information to identify the novel pathways, but it can also be used to
      decipher absolute carbon fluxes through the metabolic network of interest. This
      technique can be widely used for functional characterization of nonmodel
      microbial species, and thus we provide a (13)C-pathway and flux analysis
      protocol. The five key procedures are: (1) growing cells using labeled
      substrates, (2) measuring extracellular metabolite and biomass component, (3)
      analyzing isotopic labeling patterns in amino acids and central metabolites using
      gas chromatography-mass spectrometry, (4) tracing (13)C carbon transitions in
      metabolites and discovering new pathways, and (5) estimating flux distributions
      based on isotopomer constraints. This protocol provides complementary information
      to the recently published protocol for (13)C-based metabolic flux analysis of the
      model species Escherichia coli (Nat Protoc 4:878-892, 2009).

PMID- 22639219
TI  - Biolog phenotype microarrays.
AB  - Phenotype microarrays nicely complement traditional genomic, transcriptomic, and
      proteomic analysis by offering opportunities for researchers to ground microbial
      systems analysis and modeling in a broad yet quantitative assessment of the
      organism's physiological response to different metabolites and environments.
      Biolog phenotype assays achieve this by coupling tetrazolium dyes with minimally
      defined nutrients to measure the impact of hundreds of carbon, nitrogen,
      phosphorous, and sulfur sources on redox reactions that result from compound
      induced effects on the electron transport chain. Over the years, we have used
      Biolog's reproducible and highly sensitive assays to distinguish closely related
      bacterial isolates, to understand their metabolic differences, and to model their
      metabolic behavior using flux balance analysis. This chapter describes Biolog
      phenotype microarray system components, reagents, and methods, particularly as
      they apply to bacterial identification, characterization, and metabolic analysis.

PMID- 22639220
TI  - NanoSIP: NanoSIMS applications for microbial biology.
AB  - Recent advances in high-resolution imaging secondary ion mass spectrometry (SIMS)
      (J Biol 5: 20, 2006) have made isotopic tracing at the single-cell level a
      standard technique for microbial ecology and systems biology; elemental and metal
      cofactor analyses are also showing significant promise. For example, with the
      NanoSIMS, metabolic activities of single microbial cells can be tracked by
      imaging natural isotopic/elemental composition or isotope distribution after
      stable isotope probing. When linked to molecular visualization methods, such as
      in situ hybridization and antibody labeling, these techniques enable in situ
      function to be linked to microbial identity and gene expression. We broadly call
      this combination of methods nanoSIP, for nanometer-scale stable isotope probing.
      Here we present the primary materials and methods used for nanoSIP, with an
      emphasis on key steps and potential pitfalls. Applications to pure cultures,
      cocultures, and complex communities are discussed.

PMID- 22639221
TI  - Electrophysiological-metabolic modeling of microbes: applications in fuel cells
      and environment analysis.
AB  - A formalism for simulating coupled metabolic and electrophysiological processes
      is presented. The resulting chemical kinetic and electrophysiological equations
      are solved numerically to create a cell simulator. Metabolic features of this
      simulator were adapted from Karyote, a multi-compartment biochemical cell
      modeling simulator. We present the mathematical formalism and its computational
      implementation as an integrated electrophysiological-metabolic model.
      Applications to Geobacter sulfurreducens in the environment and in a fuel cell
      are discussed.

PMID- 22639222
TI  - Simulating microbial systems: addressing model uncertainty/incompleteness via
      multiscale and entropy methods.
AB  - Most systems of interest in the natural and engineering sciences are multiscale
      in character. Typically available models are incomplete or uncertain. Thus, a
      probabilistic approach is required. We present a deductive multiscale approach to
      address such problems, focusing on virus and cell systems to demonstrate the
      ideas. There is usually an underlying physical model, all factors in which (e.g.,
      particle masses, charges, and force constants) are known. For example, the
      underlying model can be cast in terms of a collection of N-atoms evolving via
      Newton's equations. When the number of atoms is 10(6) or more, these physical
      models cannot be simulated directly. However, one may only be interested in a
      coarse-grained description, e.g., in terms of molecular populations or overall
      system size, shape, position, and orientation. The premise of this chapter is
      that the coarse-grained equations should be derived from the underlying model so
      that a deductive calibration-free methodology is achieved. We consider a
      reduction in resolution from a description for the state of N-atoms to one in
      terms of coarse-grained variables. This implies a degree of uncertainty in the
      underlying microstates. We present a methodology for modeling microbial systems
      that integrates equations for coarse-grained variables with a probabilistic
      description of the underlying fine-scale ones. The implementation of our strategy
      as a general computational platform (SimEntropicsTM) for microbial modeling and
      prospects for developments and applications are discussed.

PMID- 22639223
TI  - Bacterial genome annotation.
AB  - Annotation of prokaryotic sequences can be separated into structural and
      functional annotation. Structural annotation is dependent on algorithmic
      interrogation of experimental evidence to discover the physical characteristics
      of a gene. This is done in an effort to construct accurate gene models, so
      understanding function or evolution of genes among organisms is not impeded.
      Functional annotation is dependent on sequence similarity to other known genes or
      proteins in an effort to assess the function of the gene. Combining structural
      and functional annotation across genomes in a comparative manner promotes higher
      levels of accurate annotation as well as an advanced understanding of genome
      evolution. As the availability of bacterial sequences increases and annotation
      methods improve, the value of comparative annotation will increase.

PMID- 22639224
TI  - LeishCyc: a guide to building a metabolic pathway database and visualization of
      metabolomic data.
AB  - The complexity of the metabolic networks in even the simplest organisms has
      raised new challenges in organizing metabolic information. To address this,
      specialized computer frameworks have been developed to capture, manage, and
      visualize metabolic knowledge. The leading databases of metabolic information are
      those organized under the umbrella of the BioCyc project, which consists of the
      reference database MetaCyc, and a number of pathway/genome databases (PGDBs) each
      focussed on a specific organism. A number of PGDBs have been developed for
      bacterial, fungal, and protozoan pathogens, greatly facilitating dissection of
      the metabolic potential of these organisms and the identification of new drug
      targets. Leishmania are protozoan parasites belonging to the family
      Trypanosomatidae that cause a broad spectrum of diseases in humans. In this work
      we use the LeishCyc database, the BioCyc database for Leishmania major, to
      describe how to build a BioCyc database from genomic sequences and associated
      annotations. By using metabolomic data generated in our group, we show how such
      databases can be utilized to elucidate specific changes in parasite metabolism.

PMID- 22639225
TI  - Development of constraint-based system-level models of microbial metabolism.
AB  - Genome-scale models of metabolism are valuable tools for using genomic
      information to predict microbial phenotypes. System-level mathematical models of
      metabolic networks have been developed for a number of microbes and have been
      used to gain new insights into the biochemical conversions that occur within
      organisms and permit their survival and proliferation. Utilizing these models,
      computational biologists can (1) examine network structures, (2) predict
      metabolic capabilities and resolve unexplained experimental observations, (3)
      generate and test new hypotheses, (4) assess the nutritional requirements of the
      organism and approximate its environmental niche, (5) identify missing enzymatic
      functions in the annotated genome, and (6) engineer desired metabolic
      capabilities in model organisms. This chapter details the protocol for developing
      genome-scale models of metabolism in microbes as well as tips for accelerating
      the model building process.

PMID- 22639226
TI  - Complex network analysis in microbial systems: theory and examples.
AB  - An essential idea in the area of Systems Biology is that a good understanding of
      interactions between components is crucial for developing deep knowledge of the
      functioning of the system as a whole. Network analysis is an approach uniquely
      suited to uncover patterns and organizing principles in a wide variety of complex
      systems. In this chapter, we will give a detailed description of central network
      concepts and their algorithmic implementation, and demonstrate how they may be
      applied on two biological networks: the protein-interaction network of Mus
      musculus and the reconstructed genome-scale metabolic network of the bacterium
      Yersinia pestis.

PMID- 22639227
TI  - Modeling a minimal cell.
AB  - One important aim of synthetic biology is to develop a self-replicating
      biological system capable of performing useful tasks. A mathematical model of a
      synthetic organism would greatly enhance its value by providing a platform in
      which proposed modifications to the system could be rapidly prototyped and
      tested. Such a platform would allow the explicit connection of genomic sequence
      information to physiological predictions. As an initial step toward this aim, a
      minimal cell model (MCM) has been formulated. The MCM is defined as a model of a
      hypothetical cell with the minimum number of genes necessary to grow and divide
      in an optimally supportive culture environment. It is chemically detailed in
      terms of genes and gene products, as well as physiologically complete in terms of
      bacterial cell processes (e.g., DNA replication and cell division). A
      mathematical framework originally developed for modeling Escherichia coli has
      been used to build the platform MCM. A MCM with 241 product-coding genes (those
      which produce protein or stable RNA products) is presented. This gene set is
      genomically complete in that it codes for all the functions that a minimal
      chemoheterotrophic bacterium would require for sustained growth and division.
      With this model, the hypotheses behind a minimal gene set can be tested using a
      chemically detailed, dynamic, whole-cell modeling approach. Furthermore, the MCM
      can simulate the behavior of a whole cell that depends on the cell's (1)
      metabolic rates and chemical state, (2) genome in terms of expression of various
      genes, (3) environment both in terms of direct nutrient starvation and
      competitive inhibition leading to starvation, and (4) genomic sequence in terms
      of the chromosomal locations of genes.

PMID- 22639228
TI  - Amygdaloid signature of peripheral immune activation by bacterial
      lipopolysaccharide or staphylococcal enterotoxin B.
AB  - Activated immune cells produce soluble mediators that not only coordinate local
      and systemic immune responses but also act on the brain to initiate behavioral,
      neuroendocrine and metabolic adaptations. Earlier studies have shown that the
      amygdala, a group of nuclei located in the medial temporal lobe, is engaged in
      the central processing of afferent signals from the peripheral immune system.
      Here, we compared amygdaloid responses to lipopolysaccharide (LPS) and
      staphylococcal enterotoxin B (SEB), two prototypic bacterial products that elicit
      distinct immune responses. Intraperitoneal administration of LPS (0.1 mg/kg) or
      SEB (1 mg/kg) in adult rats induced substantial increases in amygdaloid neuronal
      activity as measured by intracerebral electroencephalography and c-fos gene
      expression. Amygdaloid neuronal activation was accompanied by an increase in
      anxiety-related behavior in the elevated plus-maze test. However, only treatment
      with LPS, but not SEB, enhanced amygdaloid IL-1beta and TNF-alpha mRNA
      expression. This supports the view of the immune system as a sensory organ that
      recognizes invading pathogens and rapidly relays this information to the brain,
      independent of the nature of the immune response induced. The observation that
      neuronal and behavioral responses to peripheral immune challenges are not
      necessarily accompanied by increased brain cytokine expression suggests that
      cytokines are not the only factors driving sickness-related responses in the CNS.

PMID- 22639229
TI  - Comparison of the D2 receptor regulation and neurotoxicant susceptibility of
      nigrostriatal dopamine neurons in wild-type and CB1/CB2 receptor knockout mice.
AB  - Motor dysfunctions of Parkinson Disease (PD) are due to the progressive loss of
      midbrain nigrostriatal dopamine (NSDA) neurons. Evidence suggests a role for
      cannabinoid receptors in the neurodegeneration of these neurons following
      neurotoxicant-induced injury. This work evaluates NSDA neurons in CB1/CB2
      knockout (KO) mice and tests the hypothesis that CB1/CB2 KO mice are more
      susceptible to neurotoxicant exposure. NSDA neuronal indices were assessed using
      unbiased stereological cell counting, high pressure liquid chromatography coupled
      with electrochemical detection or mass spectrometry, and Western blot. Results
      reveal that CB1 and CB2 cannabinoid receptor signaling is not necessary for the
      maintenance of a normally functioning NSDA neuronal system. Mice lacking CB1 and
      CB2 receptors were found to be equally susceptible to the neurotoxicant 1-methyl
      4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). These studies support the use of
      CB1/CB2 KO mice for investigating the cannabinoid receptor-mediated regulation of
      the NSDA neuronal system in models of PD.

PMID- 22639230
TI  - The effect of continuous positive airway pressure usage on sleepiness in
      obstructive sleep apnoea: real effects or expectation of benefit?
AB  - RATIONALE: Placebo responses are complex psychobiological phenomena and often
      involve patient expectation of benefit. With continuous positive airway pressure
      (CPAP) treatment of obstructive sleep apnoea, greater hours of CPAP use are
      associated with reduced sleepiness. However, these open-label studies have not
      controlled for patient expectation of benefit derived from their knowledge of
      hours of device use. OBJECTIVES: To investigate the relative effectiveness of the
      use of real or placebo CPAP on daytime sleepiness. METHODS: Patient-level meta
      analysis combining data on sleepiness measured by the Epworth Sleepiness Scale
      from three randomised placebo-controlled crossover trials. Mixed model analysis
      of variance was used to quantify the effects of real versus placebo device
      treatment, usage, their interaction and regression to the mean. MEASUREMENTS AND
      MAIN RESULTS: Duration of real and placebo CPAP use was correlated within
      patients (r=0.53, p<0.001). High use of real CPAP reduced sleepiness more than
      high use of placebo (difference 3.0 points; 95% CI 1.7 to 4.3, p<0.001) and more
      than low use of real CPAP (difference 3.3; 95% CI 1.9 to 4.7, p<0.0001). High use
      of placebo was superior to low use of placebo (difference 1.5; 95% CI 0.1 to 2.8,
      p=0.03). Twenty-nine per cent of the effect of high usage of CPAP (4.2 points;
      95% CI 3.3 to 5.1) was explained by the expectation of benefit effect associated
      with high use of placebo (1.2 points ; 95% CI 0.2 to 2.3). CONCLUSIONS: A
      clinically significant proportion of the effectiveness of high CPAP use in
      reducing sleepiness is probably caused by patient expectation of benefit.

PMID- 22639232
TI  - Dynamic combinatorial chemistry employing boronic acids/boronate esters leads to
      potent oxygenase inhibitors.

PMID- 22639231
TI  - Permeability of eroded enamel following application of different fluoride gels
      and CO2 laser.
AB  - This study evaluated the combined effect of fluoride compounds and CO(2) laser in
      controlling the permeability of eroded enamel. Bovine enamel slabs (3 * 2 mm)
      were cycled twice through an alternating erosion and remineralization regimen.
      Slabs were immersed in 20 ml of orange juice (pH 3.84) for 5 min under agitation,
      rinsed with deionized water, and stored in artificial saliva for 4 h to form
      erosive lesions. Specimens were then divided into four groups (n = 10), which
      were treated for 1 min with either a control or with one of the following gels:
      amine fluoride (AmF), titanium tetrafluoride (TiF(4)), or sodium fluoride (NaF).
      Half of the specimens were irradiated with a CO(2) laser (lambda = 10.6 MUm; 2.0
      W). Specimens were cycled two more times through the aforementioned erosion
      remineralization regimen and were subjected to permeability assessment. ANOVA
      demonstrated a significant interaction between fluoride and laser treatment (p =
      0.0152). Tukey's test showed that when fluoride was applied alone, TiF(4)
      resulted in lower enamel permeability than that observed after application of the
      placebo gel. Intermediate permeability values were noted after NaF and AmF had
      been used. A significant reduction in enamel permeability was obtained when
      fluoride was combined with CO(2) laser treatment, with no difference between
      fluoride gels. Permeability of eroded enamel may be reduced by combining the
      application of fluoride gels with CO(2) laser irradiation.

PMID- 22639233
TI  - Polyimide/SU-8 catheter-tip MEMS gauge pressure sensor.
AB  - This paper describes the development of a polyimide/SU-8 catheter-tip MEMS gauge
      pressure sensor. Finite element analysis was used to investigate critical
      parameters, impacting on the device design and sensing characteristics. The
      sensing element of the device was fabricated by polyimide-based micromachining on
      a flexible membrane, using embedded thin-film metallic wires as piezoresistive
      elements. A chamber containing this flexible membrane was sealed using an adapted
      SU-8 bonding technique. The device was evaluated experimentally and its overall
      performance compared with a commercial silicon-based pressure sensor.
      Furthermore, the device use was demonstrated by measuring blood pressure and
      heart rate in vivo.

PMID- 22639234
TI  - Tuning the dimensions of ZnO nanorod arrays for application in hybrid
      photovoltaics.
AB  - ZnO nanorod arrays are a very eligible option as electron acceptor material in
      hybrid solar cells, owing to their favorable electrical properties and abundance
      of available, easy, and low-cost synthesis methods. To become truly effective in
      this field, a major prerequisite is the ability to tune the nanorod dimensions
      towards optimal compatibility with electron-donating absorber materials. In this
      work, a water-based seeding and growth procedure is used to synthesize ZnO
      nanorods. The nanorod diameter is tuned either by modifying the zinc
      concentration of the seeding solution or by changing the concentration of the
      hydrothermal growth solution. The consequences of this morphological tailoring in
      the performance of hybrid solar cells are investigated, which leads to a new
      record efficiency of 0.82 % for hydrothermally grown ZnO nanorods of size 300 nm
      in combination with poly(3-hexylthiophene-2,5-diyl) (P3HT). This improvement is
      attributed to a combined effect of nanorod diameter and orientation, and possibly
      to a better alignment of the P3HT backbone resulting in improved charge
      transport.

PMID- 22639235
TI  - Synthesis and study of plasmon-induced carrier behavior at Ag/TiO2 nanowires.
AB  - Nanocomposites of Ag/TiO(2) nanowires with enhanced photoelectrochemical
      performance have been prepared by a facile solvothermal synthesis of TiO(2)
      nanowires and subsequent photoreduction of Ag(+) ions to Ag nanoparticles (AgNPs)
      on the TiO(2) nanowires. The as-prepared nanocomposites exhibited significantly
      improved cathodic photocurrent responses under visible-light illumination, which
      is attributed to the local electric field enhancement of plasmon resonance effect
      near the TiO(2) surface rather than by the direct transfer of charge between the
      two materials. The visible-light-driven photocatalytic performance of these
      nanocomposites in the degradation of methylene blue dye was also studied, and the
      observed improvement in photocatalytic activity is associated with the extended
      light absorption range and efficient charge separation due to surface plasmon
      resonance effect of AgNPs.

PMID- 22639236
TI  - Fossil papio cranium from !Ncumtsa (Koanaka) Hills, western Ngamiland, Botswana.
AB  - Three fossils, a cranium of Papio, a cercopithecid frontal bone, and a mandible
      of juvenile Papio, have been recovered from cave deposits in the !Ncumtsa
      (Koanaka) Hills of western Ngamiland, Botswana. These specimens are significant
      because well-preserved crania of Papio are extremely rare in the fossil record
      outside of South Africa and because this is the first report of fossil primate
      cranial remains from Botswana. Thermoluminescence dating of surrounding cave
      matrix indicates an age of >=317 +/- 114 ka, within the Middle Pleistocene,
      although it may be older. Based on univariate and multivariate analyses, the
      adult !Ncumtsa specimen falls within the range of variation seen in extant forms
      of Papio, yet is distinct from any living species/subspecies and represents a new
      taxon, named here as a new subspecies of Papio hamadryas-Papio hamadryas
      botswanae.

PMID- 22639237
TI  - Interleukin-18 levels reflect the long-term prognosis of acute lung injury and
      acute respiratory distress syndrome.
AB  - PURPOSE: The purpose of this study was to investigate the relationship between
      the blood levels of interleukin (IL)-18 measured in the early stage of acute
      respiratory failure and the prognosis for patient survival. METHODS: The study
      subjects were 38 patients with acute respiratory failure treated at our
      institution during the 4-year period from April 2004 to March 2008. The
      underlying clinical condition was defined as acute respiratory distress syndrome
      (ARDS; n = 12) or acute lung injury (ALI; n = 26). The serum levels of
      interleukin (IL)-18, IL-12, and tumor necrosis factor (TNF)-alpha were measured
      by enzyme-linked immunosorbent assays. RESULTS: The ARDS group showed
      significantly higher serum levels of IL-18, IL-12, and TNF-alpha even at an early
      stage after disease onset compared with the ALI group. A negative correlation was
      noted between the PaO(2)/FIO(2) ratio (P/F ratio) and serum IL-18 level. Analysis
      of all 38 patients with ALI/ARDS revealed a 30-day mortality rate of 7.9 %, 60
      day mortality rate of 15.8 %, and 90-day mortality rate of 18.4 %. The early
      stage serum levels of IL-18, IL-12, and TNF-alpha were significantly higher in
      the non-survivors at 60 and 90 days, but not at 30 days, than in the
      corresponding survivors. CONCLUSION: The present data demonstrate an inverse
      correlation between serum IL-18 level and the P/F ratio, suggesting the possible
      involvement of IL-18 in the pathogenesis of respiratory failure in patients with
      ALI/ARDS. Early-stage serum IL-18, IL-12, and TNF-alpha levels appear to reflect
      the >60-day prognosis in patients with ALI/ARDS.

PMID- 22639238
TI  - Preparation of irinotecan-loaded folate-targeted liposome for tumor targeting
      delivery and its antitumor activity.
AB  - The purpose of this study was to investigate the in vivo distribution and
      antitumor activity of irinotecan (camptothecin (CPT)-11)-loaded folate-targeted
      liposome (F-Lip) in tumor-bearing mice following i.v. administration. Folate
      poly(ethylene glycol)-distearoylphosphatidylcholine (FA-PEG-DSPE) was synthesized
      by amide reaction of DSPE-PEG-NH(2) and FA. F-Lip modified by FA-PEG-DSPE was
      prepared by an ammonium sulfate gradient. The mean particle size and entrapment
      efficiency of F-Lip with negative charge were 197.8 +/- 4.58 nm and 91.39 +/-
      2.34 %, respectively. The distributions of CPT-11 and SN-38 in the tumor after
      i.v. administration of F-Lip, CPT-11-loaded liposomes (C-Lip), and CPT-11
      injection (C-Inj) were far greater with the F-Lip group in comparison to the C
      Inj and C-Lip, which might contribute to folate-meditated targeting uptake by the
      folate receptor on the surface of the tumor cells. The uptake of CPT-11 in the
      liver and rectum for two liposome groups were all markedly increased as compared
      to the C-Inj. Moreover, F-Lip exhibited a dose-dependent tumor growth inhibition
      and superior anticancer activity to C-Lip and C-Inj after i.v. administration. It
      also showed no significant body weight loss and much lower toxicity on the center
      immune organs. Therefore, F-Lip may be presented as potential candidates for
      tumor targeting drug delivery.

PMID- 22639239
TI  - The control of skin-permeating rate of bisoprolol by ion-pair strategy for long
      acting transdermal patches.
AB  - A moderate drug permeating rate (flux) is desirable for long-acting transdermal
      patches. In this work, a novel simple method of controlling bisoprolol (BSP) flux
      by ion-pair strategy was initiated. Different ion-pair complexes including
      bisoprolol maleate (BSP-M), bisoprolol tartarate, bisoprolol besilate, and
      bisoprolol fumarate were prepared and their fluxes through rabbit abdominal skin
      were determined separately in vitro. Furthermore, permeation behavior from
      isopropyl myristate, solubility index in pressure-sensitive adhesives, determined
      by DSC, and n-octanol/water partition coefficient (log P) were investigated to
      illustrate the mechanism of drug permeation rate controlling. The results showed
      that compared to free BSP (J = 25.98 +/- 2.34 MUg/cm(2)/h), all BSP ion-pair
      complexes displayed lower and controllable flux in the range of 0.11 to 4.19
      MUg/cm(2)/h. After forming ion-pair complexes, the capability of BSP to penetrate
      through skin was weakened due to the lowered log P and increased molecule weight.
      Accordingly, this study has demonstrated that the flux of BSP could be controlled
      by ion-pair strategy, and among all complexes investigated, BSP-M was the most
      promising candidate for long-acting transdermal patches.

PMID- 22639240
TI  - Design, synthesis, and in vitro antibacterial activity of fluoroquinolone
      derivatives containing a chiral 3-(alkoxyimino)-2-(aminomethyl)azetidine moiety.
AB  - A series of novel (R)/(S)-7-(3-alkoxyimino-2-aminomethyl-1
      azetidinyl)fluoroquinolone derivatives were synthesized and evaluated for their
      in vitro antibacterial activity against representative strains. Our results
      reveal that 12 of the target compounds generally show better activity (MIC:
      <0.008-0.5 MUg mL(-1)) against the tested Gram-positive strains including MRSA
      and MRSE than levofloxacin (LVFX, MIC: 0.125-8 MUg mL(-1)). Their activity is
      similar to that of gemifloxacin (GMFX, MIC: <0.008-4 MUg mL(-1)). However, they
      are generally less active than the two reference drugs against Gram-negative
      strains. Moreover, against clinical strains of S. aureus including MRSA and S.
      epidermidis including MRSE, the MIC(50) values (0.06-16 MUg mL(-1)) and MIC(90)
      values (0.5-32 MUg mL(-1)) of compounds 16 w, y, and z are 2-8- and 2-16-fold
      less than LVFX, respectively, and 16 w (MIC(90) range: 0.5-4 MUg mL(-1)) was also
      found to be more active than GMFX (MIC(90) range: 1-8 MUg mL(-1)).

PMID- 22639241
TI  - Aggregation of stabilized TiO2 nanoparticle suspensions in the presence of
      inorganic ions.
AB  - The present study aims to evaluate the effect of inorganic ions on the
      aggregation kinetics of stabilized titanium dioxide (TiO(2) ) nanoparticle (NP)
      suspension, an NP mode widely used in consumer goods and in aquatic environments.
      The point of zero charge of stabilized TiO(2) NPs was approximately pH 6.5. The
      particle size of the stabilized TiO(2) NP suspensions increased with the increase
      in salt concentrations. The additional salts caused the shift of zeta potentials
      of TiO(2) suspensions to a lower value. The TiO(2) NPs aggregated more obviously
      in the presence of anions than cations, and the effect of divalent anions was
      larger than that of monovalent anions. The critical coagulation concentration
      (CCC) values for commercial TiO(2) NP suspensions with positive surfaces were
      estimated as 290 and 2.3 meq/L for Cl(-) and SO 42-, respectively. These CCC
      values of stabilized TiO(2) NP suspensions are higher than those of TiO(2) NP
      powders, indicating greater stability of the commercial stabilized TiO(2) NP
      suspensions. The effects of commercial TiO(2) NP suspensions still need to be
      explored and defined. Derjaguin-Landau-Verwey-Overbeek (DLVO) analysis can
      explain the aggregation behaviors of stabilized TiO(2) NP suspensions. Such an
      understanding can facilitate the prediction of NP fate in the environment.

PMID- 22639242
TI  - Discriminating unipolar and bipolar depression by means of fMRI and pattern
      classification: a pilot study.
AB  - Bipolar disorders rank among the most debilitating psychiatric diseases. Bipolar
      depression is often misdiagnosed as unipolar depression, leading to suboptimal
      therapy and poor outcomes. Discriminating unipolar and bipolar depression at
      earlier stages of illness could therefore help to facilitate efficient and
      specific treatment. In the present study, the neurobiological underpinnings of
      emotion processing were investigated in a sample of unipolar and bipolar
      depressed patients matched for age, gender, and depression severity by means of
      fMRI. A pattern-classification approach was employed to discriminate the two
      samples. The pattern classification yielded up to 90 % accuracy rates
      discriminating the two groups. According to the feature weights of the
      multivariate maps, medial prefrontal and orbitofrontal regions contributed to
      classifications specific to unipolar depression, whereas stronger feature weights
      in dorsolateral prefrontal areas contribute to classifications as bipolar. Strong
      feature weights were observed in the amygdala for the negative faces condition,
      which were specific to unipolar depression, whereas higher amygdala features
      weights during the positive faces condition were observed, specific to bipolar
      subjects. Standard univariate fMRI analysis supports an interpretation, where
      this might be related to a higher responsiveness, by yielding a significant
      emotion * group interaction within the bilateral amygdala. We conclude that
      pattern-classification techniques could be a promising tool to classify acutely
      depressed subjects as unipolar or bipolar. However, since the present approach
      deals with small sample sizes, it should be considered as a proof-of-concept
      study. Hence, results have to be confirmed in larger samples preferably of
      unmedicated subjects.

PMID- 22639243
TI  - A further evaluation of decision-making under risk and under ambiguity in
      schizophrenia.
AB  - Abnormal decision-making has been described as a key-concept to understand some
      behavioral disturbances in schizophrenia. However, whether schizophrenia patients
      display impairments in profitable decision-making on experimental designs is
      still controversial (1) to assess performance on decision-making paradigms under
      ambiguity and under risk conditions in a large sample of schizophrenia patients
      and (2) to study the impact of clinical variables on decision-making performance
      in schizophrenia. The Iowa gambling task (IGT) and the game of dice task (GDT)
      were administered to assess, respectively, decision-making under ambiguity and
      under risk in 63 schizophrenia patients and 67 healthy controls. In addition,
      clinical variables (e.g., schizophrenic symptoms, self-reported depression, and
      impulsivity) were evaluated using appropriate questionnaires the same day.
      Pharmacological treatments were reported. Schizophrenia patients had impaired
      performances on both IGT and GDT tasks. No correlation between the decision
      making tasks performance and clinical variables was found. Lower gains on the GDT
      were associated with executive dysfunctioning in schizophrenia. These findings
      give evidence that schizophrenia patients display impairments in both decision
      making under ambiguity and under risk.

PMID- 22639245
TI  - Meanings of happiness among two ethnic groups living with advanced cancer in
      south London: a qualitative study.
AB  - OBJECTIVE: Happiness is a central component in quality of life but little is
      known about its meanings among people living with an advanced disease and those
      from diverse communities. This study explores and compares, for the first time,
      the centrality and interpretations of happiness across two cultural groups living
      with advanced cancer. METHODS: Semi-structured interviews among 26 Black
      Caribbean and 19 White British cancer patients were conducted in hospital and
      home settings. RESULTS: Thirty eight participants volunteered views on happiness,
      which were related to four main themes: empty lives, a theme associated with
      lives devoid of contentment; happiness and the physical form principally,
      associated with the absence of distressing symptoms; 'love and affection'
      associated with family and friends; and 'realising personal meaning in life',
      most common among the Black Caribbean participants and related to God, prayer and
      the sacred world. The presence of cancer pain even when refractory did not
      preclude manifestations of happiness in this domain. CONCLUSIONS: We identified
      that happiness was central to many patients' quality of life during advanced
      cancer. Moreover, happiness was multidimensional and at times culturally
      patterned. We recommend that health and social care professionals increase their
      awareness and skills-set in relation to exploring happiness. Further, we
      recommend greater efforts are invested in cultural relativism to service the
      physical, psychological, social and spiritual issues that contribute towards
      moments of happiness among diverse communities.

PMID- 22639244
TI  - Enhanced top-down control during pursuit eye tracking in schizophrenia.
AB  - Alterations in sensorimotor processing and predictive mechanisms have both been
      proposed as the primary cause of eye tracking deficits in schizophrenia. 20
      schizophrenia patients and 20 healthy controls were assessed on blocks of
      predictably moving visual targets at constant speeds of 10, 15 or 30 degrees /s.
      To assess internal drive to the eye movement system based on predictions about
      the ongoing target movement, targets were blanked off for either 666 or 1,000 ms
      during the ongoing pursuit movement in additional conditions. Main parameters of
      interest were eye deceleration after extinction of the visual target and residual
      eye velocity during blanking intervals. Eye deceleration after target extinction,
      reflecting persistence of predictive signals, was slower in patients than in
      controls, implying greater rather than diminished utilization of predictive
      mechanisms for pursuit in schizophrenia. Further, residual gain was not impaired
      in patients indicating a basic integrity of internal predictive models. Pursuit
      velocity gain in patients was reduced in all conditions with visible targets
      replicating previous findings about a sensorimotor transformation deficit in
      schizophrenia. A pattern of slower eye deceleration and unimpaired residual gain
      during blanking intervals implies greater adherence to top-down predictive models
      for pursuit tracking in schizophrenia. This suggests that predictive modeling is
      relatively intact in schizophrenia and that the primary cause of abnormal visual
      pursuit is impaired sensorimotor transformation of the retinal error signal
      needed for the maintenance of accurate visually driven pursuit. This implies that
      disruption in extrastriate and sensorimotor systems rather than frontostriatal
      predictive mechanisms may underlie this widely reported endophenotypes for
      schizophrenia.

PMID- 22639246
TI  - Dissecting and culturing and imaging the mouse urogenital system.
AB  - Current knowledge of the morphological and molecular events driving branching
      morphogenesis of the ureteric bud (UB) during development of the metanephric
      kidney has been greatly facilitated by the ability to explant this organ to
      culture. The UB can be further isolated from the mesenchyme and grown within a
      three-dimensional, collagen-based matrix when supplemented with the appropriate
      growth factors. The protocol presented here outlines the dissection and culture
      techniques necessary to dissect and culture the whole kidney and the isolated UB.

PMID- 22639247
TI  - In vitro culture of embryonic kidney rudiments and isolated ureteric buds.
AB  - In vitro culture of embryonic kidney rudiments has been utilized to study a
      variety of cellular processes and developmental mechanisms. Here, we describe two
      dimensional (2D) culture of embryonic kidney rudiments on Transwell filters and
      three-dimensional (3D) cultures in collagen gels in detail, and 3D culture of
      isolated ureteric bud (UB) in Matrigel with BSN-conditioned media.

PMID- 22639248
TI  - In vitro induction of nephrogenesis in mouse metanephric mesenchyme with lithium
      introduction and ureteric bud recombination.
AB  - The organ culture setup of embryonic kidney has served as a model of
      nephrogenesis for several decades. In vitro culture of the mouse metanephric
      mesenchyme enables easy manipulation and analysis of the tissue and provides
      information of cellular interactions, morphogenesis, cell differentiation, and
      molecular biology of the developmental process. The advantages of the tissue
      culture method include enhanced representativeness of situation in living
      organism compared to cell culture assays and less demanding and time-consuming
      possibilities to experimental work compared with in vivo research.

PMID- 22639249
TI  - Live imaging of the developing mouse mesonephros.
AB  - Embryonic development is a highly dynamic process involving complex tissue
      interactions and movements. Recent progress in cell labeling, image acquisition,
      and image processing technologies has brought the study of embryo morphogenesis
      to another level. It is now possible to visualize in real time the dynamic
      morphogenetic changes occurring in vivo and to reconstitute and quantify them in
      4D rendering. However, extended live embryo imaging remains challenging in terms
      of embryo survival and minimization of phototoxicity. Here, we describe a
      procedure to image the developing mesonephros for up to 16 h in intact mouse
      embryos. This method can easily be adapted to the imaging of other structures at
      similar developmental stages.

PMID- 22639250
TI  - Organotypic culture of the urogenital tract.
AB  - Organotypic culture is an invaluable technique that allows researchers with the
      tool to analyze a tissue development in an isolated and well-defined environment.
      This technique also permits one to study the roles of different signaling
      systems/signaling molecules and to take advantage of the modern real-time imaging
      techniques, including confocal microscopy. With great success, our lab has used
      organotypic culture of the urogenital tract (UGT) to study growth and extension
      of the mesonephric (Wolffian) duct and its cloaca connection, ureter maturation,
      and bladder urothelium development (Batourina et al. Nat Genet 32:109, 2002;
      Batourina et al. Nat Genet 37:1082, 2005; Mendelsohn Organogenesis 5:306, 2009).

PMID- 22639251
TI  - Live imaging kidney development in zebrafish.
AB  - The zebrafish has emerged as a powerful model to study organ development and
      regeneration. It has a number of advantages over other vertebrate model systems.
      The embryo can be kept transparent throughout embryonic development, which allows
      direct visualization of the developing organs. In addition, embryos can be easily
      manipulated surgically, genetically, or chemically. Furthermore, because nephron
      shape and function are remarkably conserved among vertebrates, zebrafish findings
      can directly inform human studies. Here, we describe a simple procedure that can
      be used by laboratories to investigate the development of zebrafish kidney and
      other organs by time-lapse microscopy.

PMID- 22639252
TI  - Analysis of 3D branching pattern: hematoxylin and eosin method.
AB  - Accurate analysis of the three-dimensional (3D) architecture of developing organs
      is critical to understanding how developmental defects can be linked with
      structural abnormalities. Here, we describe a 3D reconstruction technique of the
      developing kidney including the outer kidney capsule, ureteric epithelium, and
      developing nephrons. This 3D reconstructive process involves generating serial
      sections of the developing kidney, followed by histological staining. Each serial
      image is projected on the monitor and each tissue lineage or structure is traced.
      The kidney tracings are aligned and a 3D image is rendered. Each reconstructed
      tissue/lineage can then be subjected to quantitative analysis (e.g., surface area
      or volume). The reconstructed ureteric epithelium can be skeletonized to
      determine the branching architecture.

PMID- 22639253
TI  - Three-dimensional imaging of fetal mouse kidneys.
AB  - Three-dimensional imaging is a valuable tool for analyzing kidney growth and
      development. This technique provides information about spatial relationships
      between the branching ureteric bud, nephrons, and other structures within the
      kidney. Availability of user-friendly volume-rendering software now puts this
      technique within the capability of most laboratories with access to a confocal
      microscope. This paper describes how to prepare samples and acquire images and
      three-dimensional volume-rendered images.

PMID- 22639254
TI  - Analysis of native kidney structures in three dimensions.
AB  - Optical Projection Tomography (OPT) is an imaging technique, which has proven to
      be ideally suited to the observation and quantification of kidney development in
      rodents. Unlike confocal microscopy systems, OPT is capable of imaging the organ
      in toto across a long window of embryonic development at sufficient resolution to
      capture relative changes in branching dynamics, pelvis development, and
      nephrogenesis. Here, we describe how to image kidneys by OPT, and initial steps
      to quantify kidney development from this data.

PMID- 22639255
TI  - Estimating nephron number in the developing kidney using the physical
      disector/fractionator combination.
AB  - Design-based stereology is considered the gold-standard method for estimating the
      total number of glomeruli, and thereby nephrons, in the adult kidney. However,
      until recently, a design-based method for estimating nephron number in the
      developing kidney was not available. For such a method to provide accurate and
      precise estimates, unambiguous identification of developing nephrons is
      essential. Here, we describe a combined histochemical/stereological technique for
      estimating total nephron number in the developing mouse and rat kidney. The
      method can be modified for use in other species.

PMID- 22639256
TI  - An immunofluorescence method to analyze the proliferation status of individual
      nephron segments in the Xenopus pronephric kidney.
AB  - Organ development requires the coordination of proliferation and differentiation
      of various cell types. This is particularly challenging in the kidney, where up
      to 26 different cell types with highly specialized functions are present.
      Moreover, even though the nephron initially develops from a common progenitor
      pool, the individual nephron segments are ultimately quite different in respect
      to cell numbers. This suggests that some cells in the nephron have a higher
      proliferative index (i.e., cell cycle length) than others. Here, we describe two
      different immunofluorescence-based approaches to accurately quantify such growth
      rates in the pronephric kidney of Xenopus laevis. Rapidly dividing cells were
      identified with the mitosis marker phospho-Histone H3, while slowly cycling cells
      were labeled using the thymidine analogue EdU. In addition, individual nephron
      segments were marked using cell type-specific antibodies. To accurately assess
      the number of positively stained cells, embryos were then serially sectioned and
      analyzed by immunofluorescence microscopy. Growth rates were established by
      counting the mitosis or S-phase events in relation to the overall cells present
      in the nephron segment of interest. This experimental design is very reproducible
      and can easily be modified to fit other animal models and organ systems.

PMID- 22639257
TI  - Dissociation of embryonic kidney followed by re-aggregation as a method for
      chimeric analysis.
AB  - This chapter presents three methods for re-constructing mouse foetal kidney
      tissue from simple suspensions of cells. These techniques are very useful for a
      number of purposes: (1) they allow the production of fine-grained chimaeras in
      which cell autonomy of mutations can be tested, (2) they provide an environment
      that allows the renal differentiation potential of stem cells to be assessed, and
      (3) they are an excellent system in which to study the mechanisms of self
      organization. Each of the methods described here begins with disaggregation of
      embryonic mouse kidneys, followed by re-aggregation and culture; the main
      differences are in the culture methods, each of which has advantages for
      particular purposes.

PMID- 22639258
TI  - Analysis of migration in primary ureteric bud epithelial cells.
AB  - Kidney development has been widely used as a model system to study molecular
      control of inductive tissue interactions and mechanisms through which branching
      organs form. Due to lacking or poor methods, less focus has been in understanding
      details of cellular events that accomplish example ureteric bud (UB) branching.
      In order to form a branch point, cells need to proliferate, move in relation to
      each other, and change their shape as well as adhesive properties. In this
      chapter, detailed description is given how to set up primary UB epithelial cell
      cultures and study cell motility in these cells.

PMID- 22639259
TI  - Investigating primary cilia in cultured metanephric mesenchymal cells.
AB  - Primary cilia are present in most vertebrate cells. They have complex structures
      that are required for signal transduction in developing tissues. The embryonic
      kidney consists of two major cell lineages, ureteric and metanephric mesenchyme.
      Here, we describe a method to isolate metanephric mesenchyme from ureteric bud,
      culture metanephric mesenchyme cells, and study primary cilia in cell culture.

PMID- 22639260
TI  - Making immortalized cell lines from embryonic mouse kidney.
AB  - Immortalized cell lines derived from embryonic mouse kidneys are useful tools for
      exploring signaling pathways, morphogenetic mechanisms, and gene function in
      renal development: they also provide a means for efficient first-round screening
      of panels of small molecules intended to combat renal pathologies such as the
      development of cysts, and such cell line-based screening can allow a valuable
      reduction in the numbers of animals needed for a given line of research. This
      chapter presents a simple method for generating cell lines from the
      "Immortomouse," which carries a temperature-sensitive SV40 antigen, under the
      control of an interferon-regulated promoter.

PMID- 22639261
TI  - Engineered tissues to quantify collective cell migration during morphogenesis.
AB  - Renal development is a complex process involving the dynamic interplay of over 25
      different cell types. One distinct step in this process is the formation of the
      ureteric tree, which develops from the repeated branching of the ureteric bud.
      During branching of the ureteric bud, cells migrate collectively in unison to
      form the complex structure of the tree. Here, we present a microlithography-based
      3D culture model in which multiple identical kidney epithelial tissues are used
      to quantify collective cell migration during the process of branching
      morphogenesis.

PMID- 22639263
TI  - Isolation of high quality RNA from embryonic kidney and cells.
AB  - All the mRNAs within a cell and their relative levels are indicative of gene
      expression within that cell, which is essential for its structure and function in
      its differentiated state. Therefore, methods for the identification of the
      specific mRNAs and the quantitation of their levels are invaluable tools for
      understanding gene expression. Due to high endogenous RNase activity within
      virtually all living cells, the isolation of good quality RNA with minimal
      degradation is not a trivial task. This protocol outlines a tried and tested
      methodology for isolating high quality RNA from embryonic kidneys for various
      applications including microarray analysis and quantitative reverse transcription
      PCR (qRT-PCR).

PMID- 22639262
TI  - Access and use of the GUDMAP database of genitourinary development.
AB  - The Genitourinary Development Molecular Atlas Project (GUDMAP) aims to document
      gene expression across time and space in the developing urogenital system of the
      mouse, and to provide access to a variety of relevant practical and educational
      resources. Data come from microarray gene expression profiling (from laser
      dissected and FACS-sorted samples) and in situ hybridization at both low (whole
      mount) and high (section) resolutions. Data are annotated to a published, high
      resolution anatomical ontology and can be accessed using a variety of search
      interfaces. Here, we explain how to run typical queries on the database, by gene
      or anatomical location, how to view data, how to perform complex queries, and how
      to submit data.

PMID- 22639264
TI  - Laser capture.
AB  - This chapter describes detailed methods used for laser capture microdissection
      (LCM) of discrete subpopulations of cells. Topics covered include preparing
      tissue blocks, cryostat sectioning, processing slides, performing the LCM, and
      purification of RNA from LCM samples. Notes describe the fine points of each
      operation, which can often mean the difference between success and failure.

PMID- 22639265
TI  - Use of in situ hybridization to examine gene expression in the embryonic,
      neonatal, and adult urogenital system.
AB  - Studies into the molecular basis of morphogenesis frequently begin with
      investigations into gene expression across time and cell type in that organ. One
      of the most anatomically informative approaches to such studies is the use of in
      situ hybridization, either of intact or histologically sectioned tissues. Here,
      we describe the optimization of this approach for use in the temporal and spatial
      analysis of gene expression in the urogenital system, from embryonic development
      to the postnatal period. The methods described are applicable for high throughput
      analysis of large gene sets. As such, ISH has become a powerful technique for
      gene expression profiling and is valuable for the validation of profiling
      analyses performed using other approaches such as microarrays.

PMID- 22639266
TI  - Detection of beta-galactosidase activity: X-gal staining.
AB  - X-gal staining is a rapid and convenient histochemical technique used to detect
      reporter gene expression. A prerequisite is the creation or acquisition of
      transgenic reporter mouse lines, in which the bacterial LacZ gene has been
      knocked into the gene of interest or placed under the control of regulatory
      elements corresponding to the gene of interest. Expression is marked by a dark
      blue stain and can be detected at the single cell level, providing a robust
      visual readout of gene expression in the developing kidney. Here, we describe the
      methodology, applications, and limitations of this technique.

PMID- 22639267
TI  - Fluorescent immunolabeling of embryonic kidney samples.
AB  - This chapter provides a basic protocol to perform fluorescent immunolabeling on
      embryonic kidney samples. The procedure can be summarized in five steps:
      permeabilization, primary antibody incubation, washes, secondary antibody
      incubation, and final washes. This protocol can be used on samples of different
      origins, from thin sections to whole mounts, just by adjusting incubation times,
      temperatures, and buffer composition. Despite its simplicity, we have
      successfully and consistently used this protocol to detect the "usual suspects"
      in kidney development: CalbindinD-28k, E-cadherin, Pax2, podocalyxin, alpha-SMA,
      and Phospho-Histone H3 among others. This protocol also provides a starting point
      when trying to optimize labeling with a new antibody.

PMID- 22639268
TI  - Immunohistochemical staining of dpERK staining during early kidney development.
AB  - Signaling through the ERK/MAPK pathway within the Wolffian duct and ureteric bud
      epithelium is critical for kidney induction and branching morphogenesis. ERK
      signaling is activated by receptor tyrosine kinase such as RET and FGFR2. This
      protocol describes a method to detect the diphosphorylated form of ERK (dpERK) on
      paraffin embedded tissue of early mouse embryo.

PMID- 22639269
TI  - Sensing BMP pathway activity by immune detection of phosphorylated R-Smad
      proteins in mouse embryonic kidney.
AB  - At the onset of mammalian kidney development, the ureteric bud invades the
      surrounding metanephric mesenchyme, and genetic studies in the mouse have shown
      that BMP pathway activity has to be antagonized in the vicinity of the
      epithelium, a task performed by the secreted BMP antagonist Grem1. Here, we
      describe a short protocol that allows for detection of the pattern of BMP
      canonical signal transduction by using antibodies that specifically recognize the
      phosphorylated forms of R-Smad proteins (Smad1, Smad5, and Smad8), which provides
      a way to monitor overall pathway activity in the mammalian embryonic kidney.

PMID- 22639270
TI  - Analysis of in vivo transcription factor recruitment by chromatin
      immunoprecipitation of mouse embryonic kidney.
AB  - Chromatin immunoprecipitation (ChIP) is a powerful technique for examining
      transcription factor recruitment to chromatin, or histone modifications, at the
      level of specific genomic sequences. As such, it provides an invaluable tool for
      elucidating gene regulation at the molecular level. Combined with high-throughput
      methods such as second generation sequencing (ChIP-Seq), this technique is now
      commonly used for studying DNA-protein interactions at a genome-wide scale. The
      ChIP technique is based on covalent cross-linking of DNA and proteins with
      formaldehyde, followed by chromatin fragmentation, either enzymatic or by
      sonication, and immunoprecipitation of protein-DNA complexes using antibodies
      specific for the protein of interest. The immunoprecipitated DNA is then purified
      and the DNA sequences associated with the immunoprecipitated protein are
      identified by PCR (ChIP-PCR) or, alternatively, by direct sequencing (ChIP-Seq).
      Initially, the vast majority of ChIP experiments were performed on cultured cell
      lines. More recently, this technique has been adapted to a variety of tissues in
      different model organisms. We describe here a ChIP protocol on freshly isolated
      mouse embryonic kidneys for in vivo analysis of transcription factor recruitment
      on chromatin. This protocol has been easily adapted to other mouse embryonic
      tissues and has also been successfully scaled up to perform ChIP-Seq.

PMID- 22639271
TI  - siRNA-mediated RNA interference in embryonic kidney organ culture.
AB  - In principle, treatment of embryonic kidneys growing in organ culture with short
      interfering RNA (siRNA) offers a powerful means of investigating molecular
      function quickly and cheaply. Experiments using this approach have yielded
      significant new data, but they have also highlighted important limitations. Here,
      we briefly describe the published successes and limitations and present detailed
      instructions for two methods of siRNA treatment. The first method applies siRNA
      to intact cultured kidneys; this method is the quicker and easier of the two, but
      it is the one most affected by problems of siRNA uptake by certain renal tissues.
      The second method reduces kidney rudiments to a suspension of single cells,
      applies siRNA at that stage, when the cells are highly accessible, and then
      reaggregates the kidney; this method is more time-consuming but suffers less from
      problems of limited uptake. As well as proving instructions for the methods, we
      provide a brief discussion of necessary controls.

PMID- 22639272
TI  - Morpholino-mediated gene knockdown in mammalian organ culture.
AB  - We examined the role of semaphorin3a in ureteric bud (UB) branching morphogenesis
      using mouse metanephric organ culture [Tufro et al. (Mech Dev 125:558-568,
      2008)]. In vitro UB injection of Sema3a antisense morpholino resulted in
      increased branching morphogenesis. Cellular and tissue uptake of oligonucleotides
      was facilitated by a peptide-mediated method. Our findings were validated by in
      vitro translation and in Sema3a null mice. This chapter describes a method to
      perfuse the UB lumen with fluorescein-labeled oligonucleotides bound to a peptide
      carrier.

PMID- 22639273
TI  - Microinjection into the lumen of the ureteric tree.
AB  - During embryonic kidney development, the ureteric bud (UB) undergoes repetitive
      branching to generate the entire renal collecting system. Defects in UB branching
      result in renal malformations, from hypoplastic kidneys to renal agenesis. Mouse
      genetics has become an invaluable tool to identify gene networks regulating UB
      branching, and the recent use of embryonic chimeras has provided further insight
      into the cell-autonomous regulation of this process. However, the generation of
      these mouse models is often resource- and time-consuming. A simplified
      alternative to the generation of mouse mutants or chimeras relies on the
      modification of UB gene expression ex vivo. This chapter describes a simple
      method for microinjection into the lumen of the ureteric tree of embryonic kidney
      explants. The mouse embryonic kidney is cultured on an air-medium interface and a
      thin pulled glass needle is used to access the ureteric tree and deliver the
      reagent of choice. The applications of the technique are multiple: from simple
      labeling of the ureteric tree with fluorescent markers to overexpression or
      downregulation of specific genes by introducing viral vectors, siRNAs,
      morpholinos, or other agents.

PMID- 22639274
TI  - Renal delivery of adenovirus and antisense oligonucleotides in rats by retrograde
      renal vein injection.
AB  - Renal gene therapy may offer new strategies to treat diseases of native and
      transplanted kidneys. Several experimental techniques have been developed using
      viral, nonviral, and cellular vectors, although the effectiveness of such
      techniques varies widely depending upon the vector used, type of injection,
      species, and experimental model of renal disease. Here, we describe an optimized
      technique for renal delivery of DNA in rodents by retrograde renal vein injection
      as it is currently applied in our laboratory for adenovirus and nonviral vectors.
      This is an effective gene transfer method with lasting effect on gene expression
      in the kidney that modulates renal disease in rodents without any apparent
      harmful effect, thus having a potential therapeutic value for future clinical
      applications.

PMID- 22639275
TI  - Estimating total nephron number in the adult kidney using the physical
      disector/fractionator combination.
AB  - Nephron number has emerged as a useful parameter for assessing the roles of
      specific genes and feto-maternal environmental factors in kidney development.
      Nephron number is also of clinical interest due to increasing evidence suggesting
      that low nephron number is associated with increased risk for developing chronic
      adult disease, including cardiovascular and renal disease. The physical
      disector/fractionator combination is considered the gold standard method for
      estimating total nephron number in kidneys. Here we describe the use of this
      method to estimate total nephron number in mouse and rat kidneys, and variations
      to the method required to estimate nephron number in larger species, including
      human.

PMID- 22639276
TI  - Assessing urinary tract defects in mice: methods to detect the presence of
      vesicoureteric reflux and urinary tract obstruction.
AB  - Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) encompass a spectrum
      of kidney and urinary tract disorders. Here, we describe two assays that can be
      used to determine if a mouse has vesicoureteric reflux (VUR) or urinary tract
      obstruction, two urinary tract defects observed in CAKUT. To test for VUR, dye is
      injected into the mouse bladder and then monitored to determine if it passes
      retrogradely from the bladder towards the kidneys, indicating the presence of
      VUR. To test for urinary tract obstruction, the renal pelvis is microinjected
      with dye and its passage along the urinary tract is monitored to determine if
      there is evidence of impaired flow along the tract. These methods will facilitate
      the analysis of CAKUT phenotypes in the mouse.

PMID- 22639277
TI  - Ischemia-reperfusion injury of the mouse kidney.
AB  - Studies of the complex responses of the kidney to acute injury have yielded
      important insights into mechanisms of tissue injury and repair. A variety of
      injury models have contributed to this impressive body of knowledge, but the
      ischemia-reperfusion (IR) model has perhaps been the most widely used. This
      chapter contains a detailed method description for IR injury in the mouse
      together with notes on blood sampling and tissue harvesting. The aim of the
      chapter is to provide the novice with a step-by-step guide to establishing this
      procedure in their research program.

PMID- 22639278
TI  - Variable partial unilateral ureteral obstruction and its release in the neonatal
      and adult mouse.
AB  - Obstructive nephropathy is the most important cause of renal failure in children.
      Unilateral ureteral obstruction (UUO) in the neonatal mouse provides a useful
      model to investigate the response of the developing kidney to urine flow
      obstruction. Creation of reversible variable partial UUO (compared to complete
      UUO) more closely approximates congenital lesions, and permits the study of
      recovery following release of the obstruction. Implementation of this technique
      requires the appropriate optical, surgical, and anesthetic equipment, as well as
      adaptations appropriate to the very small animals undergoing surgical procedures.
      Care of the pups must include minimizing trauma to delicate tissues, close
      monitoring of anesthesia and body temperature, and ensuring acceptance of the
      pups by the mother. It is important to document the severity and patency of the
      partial UUO by ureteral measurement and pelvic injection of India ink. Finally,
      removal of kidneys for histologic examination should be accomplished with gentle
      handling and processing.

PMID- 22639279
TI  - Urinary diversion via cutaneous vesicostomy in the megabladder mouse.
AB  - Lower urinary tract obstruction in mice can lead to end-stage renal disease and
      death. We have developed a surgical technique to create a cutaneous vesicostomy
      in mice providing an external outlet for drainage of urine, thereby relieving the
      obstruction and slowing and/or preventing the development of end-stage renal
      disease and death.

PMID- 22639280
TI  - Ultrasound imaging of the murine kidney.
AB  - Ultrasound (US) is the most common and least invasive modality for clinical
      imaging of the kidney. One important application of US in nephrology is the
      detection and monitoring of structural changes in the kidney. Recent advances in
      US technology have facilitated the application of similar techniques to animal
      models of human disease. We have developed a simple US-based method of detection
      and quantitation of hydronephrosis in a mouse model of congenital obstructive
      nephropathy, the megabladder (mgb) mouse.

PMID- 22639282
TI  - Controlled synthesis of titanate nanodisks as versatile building blocks for the
      design of hybrid nanostructures.

PMID- 22639281
TI  - Estimating the whole bone-marrow asset in humans by a computational approach to
      integrated PET/CT imaging.
AB  - PURPOSE: Despite their relevance in clinical medicine, the extension and activity
      of the bone marrow (BM) cannot be directly evaluated in vivo. We propose a new
      method to estimate these variables by combining structural and functional maps
      provided by CT and PET. METHODS: BM extension and glucose uptake were estimated
      in 102 patients undergoing whole-body PET/CT because of a history of
      nonmetastatic melanoma. Image analysis assumed that the BM is surrounded by
      compact bone. An iterative optimization scheme was applied to each CT slice to
      identify the external border of the bone. To identify compact bone, the algorithm
      measured the average Hounsfield coefficient within a two-pixel ring located just
      inside the bone contour. All intraosseous pixels with an attenuation coefficient
      lower than this cut-off were flagged as 1, while the remaining pixels were set at
      0. Binary masks created from all CT slices were thus applied to the PET data to
      determine the metabolic activity of the intraosseous volume (IBV). RESULTS:
      Estimated whole-body IBV was 1,632 +/- 587 cm(3) and was higher in men than in
      women (2,004 +/- 498 cm(3) vs. 1,203 +/- 354 cm(3), P < 0.001). Overall, it was
      strictly correlated with ideal body weight (r = 0.81, P = 0.001) but only loosely
      with measured body weight (r = 0.43, P = 0.01). The average FDG standardized
      uptake value (SUV) in the thoracic and lumbar vertebrae was 2.01 +/- 0.36,
      Accordingly, intraosseous voxels with SUV >= 1.11 (mean spine SUV - 2.5 * SD)
      were considered as active "red" BM and those with SUV <1.11 as "yellow" BM.
      Estimated red BM volume was 541 +/- 195 ml, with a higher prevalence in the axial
      than in the appendicular skeleton (87 +/- 8 % vs. 10 +/- 8 %, P < 0.001). Again,
      red BM volume was higher in men than in women (7.8 +/- 2.2 vs. 6.7 +/- 2.1 ml/kg
      body weight, P < 0.05), but in women it occupied a greater fraction of the IBV
      (32 +/- 7 % vs. 36 +/- 10 %, P < 0.05). Patient age modestly predicted red BM
      SUV, while it was robustly and inversely correlated with red BM volume.
      CONCLUSION: Our computational analysis of PET/CT images provides a first
      estimation of the extension and metabolism of the BM in a population of adult
      patients without haematooncological disorders. This information might represent a
      new window to explore pathophysiology the BM and the response of BM diseases to
      chemotherapy.

PMID- 22639283
TI  - Varicocele in adolescence: where are we now?
AB  - The exact pathophysiology of varicocele and the subsequent alteration of
      spermatogenesis has been the subject of much debate. Despite an enormous amount
      of literature on the subject, the appropriate management of varicocele in the
      adolescent patient population has not yet been clearly elucidated. While not
      every male with varicocele will be subfertile, the possibility potentially lends
      credence to early diagnosis for those in whom treatment will have an impact.

PMID- 22639284
TI  - The SbASR-1 gene cloned from an extreme halophyte Salicornia brachiata enhances
      salt tolerance in transgenic tobacco.
AB  - Salinity severely affects plant growth and development. Plants evolved various
      mechanisms to cope up stress both at molecular and cellular levels. Halophytes
      have developed better mechanism to alleviate the salt stress than glycophytes,
      and therefore, it is advantageous to study the role of different genes from
      halophytes. Salicornia brachiata is an extreme halophyte, which grows luxuriantly
      in the salty marshes in the coastal areas. Earlier, we have isolated SbASR-1
      (abscisic acid stress ripening-1) gene from S. brachiata using cDNA subtractive
      hybridisation library. ASR-1 genes are abscisic acid (ABA) responsive, whose
      expression level increases under abiotic stresses, injury, during fruit ripening
      and in pollen grains. The SbASR-1 transcript showed up-regulation under salt
      stress conditions. The SbASR-1 protein contains 202 amino acids of 21.01-kDa
      molecular mass and has 79 amino acid long signatures of ABA/WDS gene family. It
      has a maximum identity (73 %) with Solanum chilense ASR-1 protein. The SbASR-1
      has a large number of disorder-promoting amino acids, which make it an
      intrinsically disordered protein. The SbASR-1 gene was over-expressed under CaMV
      35S promoter in tobacco plant to study its physiological functions under salt
      stress. T(0) transgenic tobacco seeds showed better germination and seedling
      growth as compared to wild type (Wt) in a salt stress condition. In the leaf
      tissues of transgenic lines, Na(+) and proline contents were significantly lower,
      as compared to Wt plant, under salt treatment, suggesting that transgenic plants
      are better adapted to salt stress.

PMID- 22639286
TI  - Undetectable sensitive serum thyroglobulin (<0.1 ng/ml) in 163 patients with
      follicular cell-derived thyroid cancer: results of rhTSH stimulation and neck
      ultrasonography and long-term biochemical and clinical follow-up.
AB  - CONTEXT: Surveillance of patients with differentiated thyroid cancer (DTC) is
      achieved using serum thyroglobulin (Tg), neck ultrasonography (US), and
      recombinant human TSH (rhTSH)-stimulated Tg (Tg-stim). OBJECTIVE: Our primary aim
      was to assess the utility of rhTSH Tg-stim in patients with suppressed Tg (Tg
      supp) below 0.1 ng/ml using a sensitive assay. Our secondary aims were to assess
      the utility of US and to summarize the profile of subsequent Tg-supp measures.
      DESIGN: This is a retrospective study conducted at two sites of an academic
      institution. PATIENTS: A total of 163 patients status after thyroidectomy and
      radioactive iodine treatment who had Tg-supp below 0.1 ng/ml and rhTSH Tg-stim
      within 60 d of each other were included. RESULTS: After rhTSH stimulation, Tg
      remained below 0.1 ng/ml in 94 (58%) and increased to 0.1-0.5 in 56 (34%), more
      than 0.5-2.0 in nine (6%), and above 2.0 ng/ml in four (2%) patients. Serial Tg
      supp levels were obtained in 138 patients followed over a median of 3.6 yr. Neck
      US were performed on 153 patients; suspicious exams had fine-needle aspiration
      (FNA). All positive FNA were identified around the time of the initial rhTSH
      test. Six of seven recurrences were detected by US (Tg-stim >2.0 ng/ml in one,
      0.8 in one and <= 0.5 in four). One stage IV patient had undetectable Tg-stim.
      CONCLUSION: In patients with DTC whose T(4)-suppressed serum Tg is below 0.1
      ng/ml, long-term monitoring with annual Tg-supp and periodic neck US are adequate
      to detect recurrences. In our experience, rhTSH testing does not change
      management and is not needed in this group of patients.

PMID- 22639285
TI  - Nucleotide enrichment of live feed: a promising protocol for rearing of Atlantic
      cod Gadus morhua larvae.
AB  - We investigated the effect of two commercial nucleotide products (NT1 and NT2),
      administered through live feed, on growth and stress tolerance of Atlantic cod
      larvae. Expression of genes related to muscle growth (igf-1, igf1r, igf-2, fst,
      fgf6, myod, and myhc) and nucleotide metabolism (uox, hprt, ndk, and uck) was
      evaluated during larval development. In addition, the expression of genes related
      to stress (hif-1alpha, hif-2alpha, hif-3alpha, and mb) was studied after an air
      exposure stress test. The enrichment of rotifers with nucleotides did not reveal
      any difference in nucleotide profiles, the exception being the RNA level of the
      NT1-enriched group that was significantly higher than the unenriched rotifer.
      Unenriched Artemia showed poor nucleotide profiles compared to enriched Artemia
      since 5' UMP, 5' GMP, and 5' AMP were observed only in the nucleotide groups. At
      38 days post-hatch (dph), NT1 group had significantly higher dry weight (3.1 +/-
      0.1 mg) than the control (CON; 2.3 +/- 0.1 mg). The treatments did not produce
      any significant differences in the expression of the key myogenic genes. Among
      the genes associated with nucleotide metabolism, ndk was down-regulated in NT1 at
      38 dph. In the air exposure test, survival was significantly higher in the CON
      (77 +/- 6 %) than in NT1 (48 +/- 3 %) and NT2 (50 +/- 3 %). After air exposure,
      mb was expressed at lower levels in NT2 group, hif-2alpha was induced in NT1
      group, and hif-3alpha was upregulated in all groups. Our findings indicate that
      the improvement in the nucleotide profile of Artemia upon nucleotide enrichment
      could eventuate in the rapid growth of larvae.

PMID- 22639287
TI  - Association of circulating sclerostin levels with fat mass and metabolic disease-
      related markers in Japanese postmenopausal women.
AB  - CONTEXT: Wnt/beta-catenin signaling is related to the pathogenesis of
      osteoporosis, diabetes, and metabolic diseases. Sclerostin is an inhibitor of
      Wnt/beta-catenin signaling. However, there are few data regarding the
      relationship between sclerostin levels and metabolic disease. OBJECTIVE: This
      study aimed to identify the relationship between serum sclerostin levels, body
      composition markers, and the markers of metabolic disease. DESIGN, SETTING, AND
      PATIENTS: The present study is a cross-sectional study. We measured serum
      sclerostin levels in 352 Japanese postmenopausal women and analyzed the
      relationship of these levels with bone mineral density, abdominal fat mass, and
      biochemical markers. The mean (sd) age of the subjects was 65.5 (9.3) yr.
      RESULTS: Serum sclerostin levels were positively correlated with percentages of
      abdominal and gynoid fat. We also analyzed the association between serum
      sclerostin levels and biochemical markers related to metabolic diseases.
      Multivariate analysis revealed that the serum sclerostin levels were
      significantly correlated with the levels of low-density lipoprotein cholesterol
      and homocysteine. CONCLUSIONS: The circulating sclerostin levels were associated
      with fat mass. The circulating sclerostin levels were also correlated with low
      density lipoprotein cholesterol and homocysteine.

PMID- 22639288
TI  - Abnormalities in muscle density and muscle function in hypophosphatemic rickets.
AB  - CONTEXT: Animal studies suggest that hypophosphatemic rickets (HPR) is associated
      with muscle function deficits, but it is unknown whether humans with HPR have a
      muscle disorder. OBJECTIVE: Our objective was to assess calf muscle size and
      density (an indicator of muscle quality) and lower extremity muscle function in
      patients with HPR. SETTING: The study was carried out in the outpatient
      department of a pediatric orthopedic hospital. PATIENTS AND OTHER PARTICIPANTS:
      Participants included 34 individuals with HPR (6-60 yr; nine males) and 34 age-
      and gender-matched controls. MAIN OUTCOME MEASURES: Calf muscle parameters
      (muscle cross-sectional area and density) were measured by peripheral
      quantitative computed tomography. Lower extremity muscle function (peak force per
      body weight and peak power per body mass) was measured by jumping mechanography
      through five tests with different levels of difficulty: multiple two-legged
      hopping, multiple one-legged hopping, single two-legged jump, chair-rise test,
      and heel-rise test. RESULTS: Compared with age- and gender-matched controls,
      patients with HPR had normal muscle size (P = 0.58) but lower muscle density (P =
      0.008) and lower peak muscle force and power (P < 0.001 in each test). Muscle
      function tests were also lower in the subgroup of patients with straight legs (n
      = 13) than in controls, even though patients with straight legs had higher muscle
      function test results than patients with severe leg deformities. CONCLUSIONS: The
      present study suggests that muscle weakness is a clinical feature of HPR. Lower
      muscle quality and limb deformities contribute to this functional deficit.

PMID- 22639289
TI  - Peri-procedural tight glycemic control during early percutaneous coronary
      intervention is associated with a lower rate of in-stent restenosis in patients
      with acute ST-elevation myocardial infarction.
AB  - OBJECTIVE: We examined the effects of peri-procedural intensive glycemic control
      (IGC) during early percutaneous coronary intervention (PCI) on restenosis rate in
      hyperglycemic patients with ST-segment elevation myocardial infarction (STEMI).
      RESEARCH DESIGN AND METHODS: A total of 165 hyperglycemic patients (glucose >=
      140 mg/dl) with first STEMI undergoing PCI were studied. Patients were randomized
      to IGC for almost 24 h after PCI (n = 82; glucose, 80-140 mg/dl) followed by
      multidose sc insulin during the hospital stay or conventional glycemic control
      (CGC; n = 83; glucose, 180-200 mg/dl) followed by conventional therapy. Coronary
      angiography was performed at study entry and at 6-month follow-up. Blood samples
      for glycemia, hemoglobin A1c, inflammatory markers (C-reactive protein and TNF
      alpha), monocyte chemoattractant-protein-1, and oxidative stress (nitrotyrosine)
      were collected immediately before and 24 h, 30 and 180 d after PCI. RESULTS:
      After insulin infusion, mean plasma glucose during the peri-procedural period was
      greater in the CGC group than in the IGC group (CGC, 191 +/- 15 mg/dl; IGC, 145
      +/- 35 mg/dl; P < 0.001). After the insulin infusion period, the levels of
      markers of oxidative stress (nitrotyrosine), inflammation (C-reactive protein,
      TNF-alpha), and monocyte chemoattractant-protein-1 were significantly higher in
      CGC patients compared with IGC patients. Moreover, ICG during PCI reduces
      restenosis by half (48 and 24%) at 6 months. During follow-up, there was no
      difference in mortality rates, glucose, inflammatory and oxidative stress markers
      among the groups. In-stent restenosis was positively associated with mean plasma
      glucose levels as well as oxidative stress and inflammatory markers during the
      insulin infusion period. CONCLUSIONS: In hyperglycemic patients with STEMI,
      optimal peri-procedural glycemic control by reducing oxidative stress and
      inflammation may improve the outcome after PCI.

PMID- 22639290
TI  - Severe hypertriglyceridemia in pregnancy.
AB  - CONTEXT: Pregnancy-related hypertriglyceridemia is rare, but it can be life
      threatening in some patients with genetic susceptibility. Complications can
      include acute pancreatitis, hyperviscosity syndrome, and possibly preeclampsia.
      We present a case of successful management of recurrent gestational
      chylomicronemia due to compound heterozygous mutations in the LPL gene. EVIDENCE
      ACQUISITION: To outline advances in clinical management of this condition, we
      searched English language publications in PubMed, EMBASE, and ISI Web of Science
      (search terms: pregnancy, pregnancy complications, pregnan*,
      hyperlipoproteinemia, hypertriglyceridemia, chylomicrons, chylomicronemia) and
      reference lists of relevant published articles from 2002 to 2011. We identified
      eight case reports. EVIDENCE SYNTHESIS: Interventions reported in those cases are
      reviewed including: 1) low-fat diet; 2) nutritional supplements; 3) oral
      prescription medications; 4) parenteral heparin; 5) insulin infusion in the
      context of hyperglycemia; and 6) therapeutic plasma exchange. CONCLUSIONS:
      Overall, our recommendations are to monitor for pregnancy-related
      hypertriglyceridemia in those with prepregnancy fasting triglyceride level
      greater than 4 mmol/liter and to institute therapy when triglyceride level
      increases to more than 10 mmol/liter. Therapy should include a multidisciplinary
      team to address dietary fat restriction, appropriate supplements, and possible
      medications when needed. Admission to hospital is recommended in severe cases. We
      conclude that complications are preventable with appropriate and timely
      intervention.

PMID- 22639291
TI  - The utility of serum thyroglobulin measurement at the time of remnant ablation
      for predicting disease-free status in patients with differentiated thyroid
      cancer: a meta-analysis involving 3947 patients.
AB  - CONTEXT: Decisions regarding initial therapy and subsequent surveillance in
      patients with differentiated thyroid cancer (DTC) depend upon an accurate
      assessment of the risk of persistent or recurrent disease. OBJECTIVE: The
      objective of this study was to examine the predictive value of a single
      measurement of serum thyroglobulin (Tg) just before radioiodine remnant ablation
      (preablation Tg) on subsequent disease-free status. DATA SOURCES: Sources
      included MEDLINE and BIOSYS databases between January 1996 and June 2011 as well
      as data from the author's tertiary-care medical center. STUDY SELECTION: Included
      studies reported preablation Tg values and the outcome of initial therapy at
      surveillance testing or during the course of long-term follow-up. DATA
      EXTRACTION: Two investigators independently extracted data and rated study
      quality using the Quality Assessment of Studies of Diagnostic Accuracy included
      in Systematic Reviews-2 (QUADAS-2) tool. DATA SYNTHESIS: Fifteen studies
      involving 3947 patients with DTC were included. Seventy percent of patients had
      preablation Tg values lower than the threshold value being examined. The negative
      predictive value (NPV) of a preablation Tg below threshold was 94.2 (95%
      confidence interval = 92.8-95.3) for an absence of biochemical or structural
      evidence of disease at initial surveillance or subsequent follow-up. The summary
      receiver operator characteristic curve based on a bivariate mixed-effects
      binomial regression model showed a clustering of studies using a preablation Tg
      below 10 ng/ml near the summary point of optimal test sensitivity and
      specificity. CONCLUSION: Preablation Tg testing is a readily available and
      inexpensive tool with a high NPV for future disease-free status. A low
      preablation Tg should be considered a favorable risk factor in patients with DTC.
      Further study is required to determine whether a low preablation Tg may be used
      to select patients for whom radioiodine remnant ablation can be avoided.

PMID- 22639292
TI  - Suspicious cervical lymph nodes detected after thyroidectomy for papillary
      thyroid cancer usually remain stable over years in properly selected patients.
AB  - CONTEXT: The risk of loco-regional recurrence in papillary thyroid cancer (PTC)
      patients ranges from 15-30%. However, the clinical significance of small-volume
      loco-regional recurrence detected by highly sensitive ultrasonography is unclear.
      OBJECTIVE: Our objective was to describe the natural history of abnormal cervical
      lymph nodes (LN) diagnosed after initial treatment. DESIGN: We conducted a
      retrospective cohort study. PATIENTS: 166 PTC with patients who had at least one
      abnormal LN outside the thyroid be on ultrasound and selected for active
      surveillance were included. MAIN OUTCOME MEASURE: LN growth during a period of
      active surveillance was the primary outcome. RESULTS: Most patients had classical
      PTC (85%) and an intermediate risk of recurrence (77%). The median LN size at the
      start of the observation period was 1.3 cm (range, 0.5-2.7 cm) in largest
      diameter, with all nodes having at least one abnormal sonographic characteristic
      (70% of patients had LN with at least two abnormal features). In almost all
      patients, the LN were in the lateral neck, primarily in levels 3 (43%) and 4
      (58%). After a median follow-up of 3.5 yr, only 20% (33 of 166) grew at least 3
      mm, 9% (15 of 166) grew at least 5 mm, and 14% (23 of 166) resolved. None of the
      clinical or sonographic features were predictive of LN growth (positive
      predictive value range = 0.21-0.57). There were no local complications (nerve
      damage or local invasion) related to the abnormal nodes and no disease-related
      mortality. CONCLUSIONS: Suspicious cervical LN in the lateral neck usually remain
      stable for long periods of time in properly selected PTC patients and can be
      safely followed with serial ultrasounds.

PMID- 22639294
TI  - A case of severe 1,25-dihydroxyvitamin D-mediated hypercalcemia due to a
      granulomatous disorder.
AB  - BACKGROUND: Profound hypercalcemia is usually due to underlying malignancy. CASE:
      We describe a case of granulomatous myositis presenting with extreme
      hypercalcemia of 20.1 mg/dl and generalized weakness that did not resolve despite
      rapid correction of serum calcium. The disease process was unmasked by
      cholecalciferol supplementation. Initial search for a malignant process yielded
      no diagnosis, but an elevated 1,25-dihydroxyvitamin D level, in the setting of a
      suppressed PTH and undetectable PTHrP, pointed to the presence of excessive
      1alpha-hydroxylase activity. METHODS AND RESULTS: Biopsy of the vastus lateralis
      muscle showed extensive granulomatous myositis. Immunohistochemical staining for
      1alpha-hydroxylase was localized to the multinucleated giant cells and
      histiocytes. Musculoskeletal magnetic resonance imaging showed involvement of
      proximal muscle groups of both thighs and upper limbs. CONCLUSION: Measurement of
      vitamin D metabolites is pivotal in diagnosing 1,25-dihydroxyvitamin D-mediated
      hypercalcemia. Granulomatous disease can occasionally cause profound
      hypercalcemia and needs to be considered in the differential diagnosis. 1,25
      Dihydroxyvitamin D-mediated hypercalcemia is responsive to glucocorticoid
      therapy.

PMID- 22639293
TI  - Acute free fatty acid elevation eliminates endurance training effect on insulin
      sensitivity.
AB  - CONTEXT: Both training and normal body mass index are associated with high
      insulin sensitivity, but the mechanism may be different. OBJECTIVE: The aim of
      the study was to examine whether lean trained humans may be protected from acute
      free fatty acid (FFA)-induced insulin resistance compared with lean sedentary
      humans. DESIGN AND SETTING: We conducted an interventional trial using either a 6
      h lipid (20% Intralipid at 90 ml/h) or glycerol (2.25 g/100 ml at 90 ml/h)
      infusion along with a concurrent hyperinsulinemic-euglycemic clamp and serial
      muscle biopsies (0, 120, 360 min) at a clinical research unit at the University
      of Minnesota. PATIENTS OR PARTICIPANTS: The study included lean endurance-trained
      (n = 14) and sedentary (n = 14) individuals matched for age, gender, and body
      mass index. MAIN OUTCOME MEASURES: We measured the decline in glucose infusion
      rate (GIR) during the hyperinsulinemic-euglycemic clamp. RESULTS: The trained
      group had higher baseline mitochondrial DNA copy number, mRNA of cytochrome C
      oxidase subunit 3, and insulin sensitivity (as measured by GIR) compared with the
      sedentary group. When FFA was acutely elevated to the upper physiological range
      (0.6-0.7 mEq/liter) by lipid infusion, the GIR in both activity groups declined
      similarly compared with their respective glycerol controls, although insulin
      signaling, as measured by Ser 473 pAKT/AKT, remained comparable. Specific to the
      trained group, the stimulatory effect of hyperinsulinemia on mitochondrial mRNA
      levels during the glycerol infusion was absent during the lipid infusion.
      CONCLUSIONS: Elevated FFA had similar effects in reducing insulin sensitivity in
      trained and sedentary humans. In trained participants, this decline was
      associated with alterations in the skeletal muscle mitochondrial mRNA response to
      hyperinsulinemia.

PMID- 22639295
TI  - Activity patterns in New Kingdom Nubia: an examination of entheseal remodeling
      and osteoarthritis at Tombos.
AB  - The effects of Egyptian imperial expansion into Nubia during the New Kingdom
      Period (1,550-1,069 BC) have been debated. Here, the impacts of the Egyptian
      Empire are investigated through an examination of osteological indicators of
      activity at the archaeological site of Tombos. Entheseal changes to
      fibrocartilaginous attachment sites and osteoarthritis are examined to infer what
      types of physical activities this colonial town was engaging in. Many of the
      skeletal remains at Tombos were commingled due to looting in antiquity;
      undisturbed burials are presented as a subsample of the population (n = 28) in
      which age, sex, and body size can be considered. The total sample (n = 85) is
      then analyzed to better understand overall levels of activity. A number of Nile
      River Valley bioarchaeological samples are used as points of comparison to the
      Tombos population. Results indicate that the inhabitants of Tombos had relatively
      low entheseal remodeling scores; this is highlighted when Tombos is juxtaposed
      with comparative samples, particularly in men. Furthermore, osteoarthritis, as
      assessed by eburnation, was also markedly infrequent at Tombos. Collectively,
      these results indicate a relatively low level of activity and support the
      hypothesis that Tombos may have served as an administrative center.

PMID- 22639296
TI  - Interstudy reproducibility of the second generation, Fourier domain optical
      coherence tomography in patients with coronary artery disease and comparison with
      intravascular ultrasound: a study applying automated contour detection.
AB  - Recently, Fourier domain OCT (FD-OCT) has been introduced for clinical use. This
      approach allows in vivo, high resolution (15 micron) imaging with very fast data
      acquisition, however, it requires brief flushing of the lumen during imaging. The
      reproducibility of such fast data acquisition under intracoronary flush
      application is poorly understood. To assess the inter-study variability of FD-OCT
      and to compare lumen morphometry to the established invasive imaging method,
      IVUS. 18 consecutive patients with coronary artery disease scheduled for PCI were
      included. In each target vessel a FD-OCT pullback (MGH system, light source 1,310
      nm, 105 fps, pullback speed 20 mm/s) was acquired during brief (3 s) injection of
      X-ray contrast (flow 3 ml/s) through the guiding catheter. A second pullback was
      repeated under the same conditions after re-introduction of the FD OCT catheter
      into the coronary artery. IVUS and OCT imaging was performed in random order. FD
      OCT and IVUS pullback data were analyzed using a recently developed software
      employing semi automated lumen contour and stent strut detection algorithms.
      Corresponding ROI were matched based on anatomical landmarks such as side
      branches and/or stent edges. Inter-study variability is presented as the absolute
      difference between the two pullbacks. FD-OCT showed remarkably good
      reproducibility. Inter-study variability in native vessels (cohort A) was very
      low for mean and minimal luminal area (0.10 +/- 0.38, 0.19 +/- 0.57 mm(2),
      respectively). Likewise inter-study variability was very low in stented coronary
      segments (cohort B) for mean lumen, mean stent, minimal luminal and minimal stent
      area (0.06 +/- 0.08, 0.07 +/- 0.10, 0.04 +/- 0.09, 0.04 +/- 0.10 mm(2),
      respectively). Comparison to IVUS morphometry revealed no significant
      differences. The differences between both imaging methods, OCT and IVUS, were
      very low for mean lumen, mean stent, minimal luminal and minimal stent area (0.10
      +/- 0.45, 0.10 +/- 0.36, 0.26 +/- 0.54, 0.05 +/- 0.47 mm(2), respectively). FD
      OCT shows excellent reproducibility and very low inter-study variability in both,
      native and stented coronary segments. No significant differences in quantitative
      lumen morphometry were observed between FD-OCT and IVUS. Evaluating these results
      suggest that FD-OCT is a reliable imaging tool to apply in longitudinal coronary
      artery disease studies.

PMID- 22639297
TI  - BMP-2 and TGF-beta3 do not prevent spontaneous degeneration in rabbit disc
      explants but induce ossification of the annulus fibrosus.
AB  - INTRODUCTION: Different approaches for disc regeneration are currently under
      investigation. Beside gene therapy and tissue engineering techniques, the
      application of growth and differentiation factors own promising potential.
      Studies using reduced intervertebral disc models, such as cell or tissue fragment
      cultures, have limited validity and show controversial results depending on the
      employed experimental model. Therefore, the goal of the current study was to
      investigate the effect of BMP-2 and TGF-beta3 on intervertebral disc degeneration
      using an in vitro full-organ disc/endplate culture system. MATERIALS AND METHODS:
      Intervertebral rabbit disc explants were cultured in the presence of 1 MUg/ml BMP
      2 or TGF-beta3 for 21 days in DMEM/F12 media. Nucleus and annulus were analyzed
      for gene expression of collagen type I and II (Col I/II), aggrecan, collagenases
      (MMP-1/MMP-13) with RT-qPCR, histological changes with bone and proteoglycan
      specific staining (von Kossa, toluidine blue) and differences in cellularity
      (DNA) and proteoglycan content (alcian blue binding assay). RESULTS: The results
      demonstrate that disc proteoglycan concentration decreased with time in the TGF
      beta3 and BMP-2 groups. In the annulus fibrosus (AF), TGF-beta3 and BMP-2
      resulted in an up-regulation of Col I and type II, and of aggrecan gene
      expression. In contrast, MMP genes were inhibited. In the nucleus, the growth
      factors decreased gene expression of aggrecan and spontaneous Col I up-regulation
      was inhibited by TGF-beta3, whereas expression of Col II was decreased with BMP
      2. There was no effect on expression of MMP-1 and MMP-13 for most sampling
      points. However, TGF-beta3 and BMP-2 induced ossification of the AF was
      demonstrated by histology. CONCLUSION: It can be concluded that both growth
      factors, at the tested concentrations, may not be suitable to regenerate the
      whole intervertebral disc organ but they are interesting candidates for being
      injected alone or in combination into a painful intervertebral disc to induce
      osseous fusion (spondylodesis).

PMID- 22639298
TI  - Comparative study of spinopelvic sagittal alignment between patients with and
      without degenerative spondylolisthesis.
AB  - INTRODUCTION: To date, few studies have focused on spinopelvic sagittal alignment
      as a predisposing factor for the development of degenerative spondylolisthesis
      (DS). The objectives of this study were to compare differences in spinopelvic
      sagittal alignment between patients with or without DS and to elucidate factors
      related to spinopelvic sagittal alignment. MATERIALS AND METHODS: A total of 100
      patients with or without DS who underwent surgery for lumbar spinal canal
      stenosis were assessed in this study. Fifty patients with DS (DS group) and 50
      age- and gender-matched patients without DS (non-DS group) were enrolled.
      Spinopelvic parameters including pelvic incidence (PI), sacral slope (SS), pelvic
      tilt (PT), L4 slope, L5 slope, thoracic kyphosis (TK), lumbar lordosis (LL) and
      sagittal balance were compared between the two groups. In the DS group, the
      percentage of vertebral slip (% slip) was also measured. RESULTS: Several
      spinopelvic parameters, PI, SS, L4 slope, L5 slope, TK and LL, in the DS group
      were significantly greater than those in the non-DS group, and PI had positive
      correlation with % slip (r = 0.35, p < 0.05). Degrees of correlations among
      spinopelvic parameters differed between the two groups. In the DS group, PI was
      more strongly correlated with SS (r = 0.82, p < 0.001) than with PT (r = 0.41, p
      < 0.01). In the non-DS group, PI was more strongly correlated with PT (r = 0.73,
      p < 0.001) than with SS (r = 0.38, p < 0.01). CONCLUSIONS: Greater PI may lead to
      the development and the progression of vertebral slip. Different compensatory
      mechanisms may contribute to the maintenance of spinopelvic sagittal alignment in
      DS and non-DS patients.

PMID- 22639299
TI  - Development of a per-operative procedure for concentrated bone marrow adjunction
      in postero-lateral lumbar fusion: radiological, biological and clinical
      assessment.
AB  - PURPOSE: Addition of bone marrow to the bone graft in the postero-lateral lumbar
      arthrodesis is a widely used technique. Bone marrow brings stem cells and growth
      factors contained in the platelets, favorable for bone growth. Adjunction of
      concentrated bone marrow should create better conditions and may increase bone
      growth. METHODS: Simple blind randomized clinical, prospective, monocentric trial
      was conducted. Fifteen patients underwent lumbar arthrodesis. During surgery, a
      fraction of the bone marrow harvested was centrifuged. One side received this
      concentrate with autologous bone and ceramics; the other side received the same
      graft with unconcentrated bone marrow. A quantitative study, realised with a
      volume calculating software on CT-scan images, determined the cortical bone
      volume in the graft post-operatively and at 3 months. The osteoprogenitor cells,
      nucleated cells and platelet concentrations were determined. RESULTS: The
      biological study found an average concentration of six times for the nucleated
      cells, 3.5 times for the platelets and 2.2 times for the osteoprogenitor cells.
      The comparison of the mean cortical bone volumes post-operatively and at 3 months
      was not significantly different. CONCLUSIONS: Despite the concentration obtained,
      there was no increase of bone growth by adding concentrated bone marrow. However,
      the number of stem cells in bone marrow was low and maybe a stronger
      concentration is needed to obtain a difference. The 3D reconstruction of the
      graft and the analysis of the graft's volume using a novel software was efficient
      according to the similarity of the graft's volume post-operatively in all
      patients.

PMID- 22639300
TI  - Relevance of expandable titanium cage for the treatment of cervical spondylotic
      myelopathy.
AB  - BACKGROUND: In patients with cervical spondylotic myelopathy, ventral disease and
      loss of physiological cervical lordosis are indications for anterior approach. As
      bone graft and titanium cage present many drawbacks, expandable titanium cage has
      been recently introduced for this indication. The authors present the clinical
      and radiological outcomes in patients undergoing the placement of an expandable
      cage in the treatment of spondylotic myelopathy with straight or kyphotic
      cervical spine alignment. METHODS: This was a retrospective review of
      prospectively collected data. A total of 26 patients underwent cervical
      corpectomy and reconstruction using an expandable titanium cage and anterior
      plate between 2005 and 2008. Pain and functional disability were measured using
      VAS and mJOA preoperatively and at 3 months, 6 months, 1 year and 2 years.
      Kyphosis was measured using lateral radiographs at the same points of follow-up.
      Fusion was evaluated on flexion-extension radiographs at 2 years. RESULTS: The
      mean VAS improved from 4.2 to 1.7 and the mean mJOA increased from 12.85 to 16.04
      at 2 years postoperatively (p < 0.05). The mean kyphosis angle decreased from 17
      degrees  to 2 degrees  at the last follow-up (p < 0.05). The fusion rate was 100%
      at 2 years. Three complications were reported including a transient dysphagia, an
      epidural hematoma and an early hardware migration. CONCLUSION: Expandable
      titanium cage is an effective device, which achieves good clinical and
      radiological outcomes at a minimum 2-year follow-up.

PMID- 22639301
TI  - Theoretical study of the oxidation of histidine by singlet oxygen.
AB  - Herein we present a theoretical study of the reaction of singlet oxygen with
      histidine performed both in the gas phase and in aqueous solution. The potential
      energy surface of the reactive system was explored at the B3LYP/cc-pVTZ level of
      theory and the electronic energies were refined by means of single-point
      CCSD(T)/cc-pVTZ(-f) calculations. Solvent effects were taken into account by
      using a solvent continuum model (COSMO) and by adding explicit water molecules.
      The results show that the first step in the reaction mechanism corresponds to a
      nearly symmetric Diels-Alder addition of the singlet oxygen molecule to the
      imidazole ring to yield an endoperoxide, in agreement with experimental evidence.
      The intermediate formed can evolve along two different reaction paths leading to
      two isomeric hydroperoxides and, eventually, to open-chain or internally cyclised
      oxidised products. Water plays a significant role in stabilising the reaction
      structures by solvation and by acting as a bifunctional catalyst in the
      elimination/addition reaction steps. Our results explain why substituents at the
      N1-imidazole ring can hamper the evolution of the initial endoperoxide and result
      in Gibbs energy barriers in solution similar to those experimentally measured and
      suggest a likely route to the formation of peptide aggregates during the
      oxidation of histidine by singlet molecular oxygen.

PMID- 22639302
TI  - Gene expression profile in bone of diabetes-prone BB/OK rats fed a high-fat diet.
AB  - A high-fat diet (HFD) has been recognized as a risk factor for diseases such as
      dyslipidemia, atherosclerosis, obesity, and osteoporosis. However, studies
      analyzing gene expression after HFD in bone are rare. That prompted us to analyze
      the expression of selected genes in bone of 4-week-old diabetes-prone
      B(io)B(reeding) rats. Two breeding pairs were fed a HFD (+10 % tallow) or were
      fed a normal diet (ND; Ssniff R-Z) before mating and afterward during pregnancy.
      After the birth of progeny, parents continued to be given HFD or ND until the
      progeny was weaned (3 weeks). Thereafter, offspring were weaned and were fed the
      same food as their parents up to an age of 4 weeks. Body weight was measured at
      an age of 4 weeks, and subsequently 13 HFD rats and 13 ND rats were killed and
      the tibial bone was harvested to analyze the expression of 53 genes in bone. All
      rats fed HFD were significantly heavier than rats fed ND after 3 and 4 weeks. The
      diet also influenced the expression of genes in bone. There were significant
      differences in 20 out of 53 genes studied between rats fed HFD compared with rats
      fed ND. Four out of 20 had a lower and 17 out of 20 genes a higher expression in
      HFD rats, but differences in gene expression showed obvious differences between
      males and females. There were only two genes that were similarly different
      between males and females: Bmp4 and Atf4. Two genes, Foxg1 and Npy, were
      inversely expressed in males and females. It seems that the gene expression is
      differently regulated by diet during pregnancy and later in life between males
      and females. Nevertheless, it cannot be excluded that HFD also acts as an
      epigenetic factor in the development of offspring in utero.

PMID- 22639303
TI  - Sensitive detection of small molecule-protein interactions on a metal-insulator
      metal label-free biosensing platform.
AB  - The need to develop label-free biosensing devices that enable rapid analyses of
      interactions between small molecules/peptides and proteins for post-genomic
      studies has increased significantly. We report a simple metal-insulator-metal
      (MIM) geometry for fabricating a highly sensitive detection platform for
      biosensing. MIM substrates consisting of an Au-PMMA-Ag nanolayer were extensively
      studied using both theoretical and experimental approaches. By monitoring
      reflectivity changes at the normal incidence angle, we observed molecular
      interactions as the thickness of the biolayer increased on the substrate surface.
      These interactions included the adsorption of various proteins (Mw=6-150 kD) and
      interactions between small molecules (Mw<=2 kD) and the immobilized proteins. The
      interaction of designed monosaccharide-modified designed peptides with various
      lectins was also clearly detected. These interactions could not be detected by
      the conventional Au-only substrate. Thus, the MIM approach affords a powerful
      label-free biosensing device that will aid our understanding of protein
      interactions and recognition.

PMID- 22639304
TI  - Estimated yield of double-strand breaks from internal exposure to tritium.
AB  - Internal exposure to tritium may result in DNA lesions. Of those, DNA double
      strand breaks (DSBs) are believed to be important. However, experimental and
      computational data of DSBs induction by tritium are very limited. In this study,
      microdosimetric characteristics of uniformly distributed tritium were determined
      in dimensions of critical significance in DNA DSBs. Those characteristics were
      used to identify other particles comparable to tritium in terms of microscopic
      energy deposition. The yield of DSBs could be strongly dependent on biological
      systems and cellular environments. After reviewing theoretically predicted and
      experimentally determined DSB yields available in the literature for low-energy
      electrons and high-energy protons of comparable microdosimetric characteristics
      to tritium in the dimensions relevant to DSBs, it is estimated that the average
      DSB yields of 2.7 * 10(-11), 0.93 * 10(-11), 2.4 * 10(-11) and 1.6 * 10(-11) DSBs
      Gy(-1) Da(-1) could be reasonable estimates for tritium in plasmid DNAs, yeast
      cells, Chinese hamster V79 cells and human fibroblasts, respectively. If a
      biological system is not specified, the DSB yield from tritium exposure can be
      estimated as (2.3 +/- 0.7) * 10(-11) DSBs Gy(-1) Da(-1), which is a simple
      average over experimentally determined yields of DSBs for low-energy electrons in
      various biological systems without considerations of variations caused by
      different techniques used and obvious differences among different biological
      systems where the DSB yield was measured.

PMID- 22639305
TI  - [The presence of extended spectrum beta-lactamase, KPC-type carbapenemase and
      plasmid-mediated AmpC beta-lactamase in E.coli and K.pneumoniae strains isolated
      from blood cultures].
AB  - The aim of this study was to investigate the presence of extended spectrum beta
      lactamase (ESBL), KPC-type carbapenemase and plasmid-mediated AmpC beta-lactamase
      (pAmpC) which have increased in incidence in recent years in Escherichia coli and
      Klebsiella pneumoniae strains isolated from the blood samples causing serious
      infections. Ninety nine E.coli and 114 K.pneumoniae strains which were isolated
      from the blood samples of patients admitted to Hacettepe University Medical
      Faculty, Ihsan Dogramaci Children's Hospital between January 2001 and March 2009
      were investigated. The screening tests for ESBL, pAmpC beta-lactamase and KPC
      type carbapenemase were performed on the same plate. Combined disk test was
      performed for ESBL and modified Hodge test was done for KPC-type carbapenemase
      confirmation according to Clinical and Laboratory Standards Institute (CLSI)
      guidelines. In addition the inhibitory-based test with boronic acid for KPC-type
      carbapenemase, pAmpC beta-lactamase and the modified Hodge test for pAmpC beta
      lactamase were performed. Boronic acid inhibition test was performed to detect
      the co-presence of the three types of resistance. The frequency of the beta
      lactamases in E.coli and K.pneumoniae isolates were as follows respectively: ESBL
      26.2% and 61.4%; pAmpC 1% and 0.9% and ESBL + pAmpC 6% and 3.5%. ESBL was masked
      by pAmpC in an isolate. Ertapenem resistance was shown in three isolates and KPC
      type carbapenemases were detected positive by the inhibitory- based test with
      boronic acid but found to be negative by the modified Hodge test. The results of
      modified Hodge test was considered valid according to CLSI comments. Since both
      ESBL and pAmpC were positive but modified Hodge test was negative in these three
      strains, ertapenem resistance was attributed to another mechanism. For the
      determination of ESBL and pAmpC beta-lactamases in the routine laboratory,
      reliable and sensitive susceptibility tests should be performed. The inhibitory
      based test with boronic acid is easy for interpretation, and a practical method
      for the detremination of pAmpC beta lactamases. For KPC-type carbapenemases
      modified Hodge test which has been standardized by CLSI, is a reliable method.
      The results of this study showed that ESBL positivity rates are alarming and
      although the frequency of pAmpC is currently low, it is increasing together with
      ESBL. These data indicated the need for the establishment of urgent measures to
      control the increase in plasmid-mediated antibiotic resistance in gram-negative
      enteric bacteria.

PMID- 22639306
TI  - [The rare genes related to resistance to macrolide-lincosamide and streptogramin
      B group antibiotics among coagulase-negative staphylococci].
AB  - Macrolide-lincosamide-streptogramin B (MLSB) group antibiotics are recommended as
      first choice in the treatment of staphylococcal infections. All of those drugs
      bind to the 50S subunit of bacterial ribosomes, thus cross-resistance is a major
      concern in this group of drugs. The mechanisms associated to resistance are (a)
      ribosomal methylation due to the methylases encoded by erm genes, (b) active drug
      efflux due to msrA, msrB, vga, vgb gene activity, (c) enzymatic inactivation of
      the drug due to the activity of linA, vat, vatB genes. While the most common
      resistance genes are ermA, ermB, ermC, msrA and msrB genes; linA, vga, vgb, vat
      and vatB genes have also been found in some studies. In this study it was aimed
      to investigate the presence of the rare MLSB resistance genes and their
      coexistence with erm and msr genes in 454 clinical isolates of coagulase-negative
      staphylococci (CNS). Of them 46.5% (n= 211) were S.hominis, 30.8% (n= 140) were
      S.epidermidis, 12.1% (n= 55) were S.haemolyticus, 3.5% (n= 16) were S.warnerii
      and 7% (n= 32) were the other coagulase-negative staphylococcal species.
      Resistance phenotypes were determined by using D-test method according to the
      recommendation of Clinical and Laboratory Standards Institute (CLSI). With the D
      test 107 (23.6%) strains were determined as M phenotype (resistant to
      erythromycin and inducible clindamycin resistance was not detected), 92 (20.3%)
      were iMLSB phenotype (inducible clindamycin resistance was detected by the D
      test) and 110 (24.2%) were cMLSB phenotype (constitutive erythromycin and
      clindamycin resistance was detected). linA, vga, vgb, vat, vatB, ermA, ermB,
      ermC, msrA, msrB genes were investigated by polymerase chain reaction in all
      strains showing iMLSB (n= 92) and cMLSB (n= 110) phenotypes and 46 randomly
      selected strains among 107 strains exhibiting the M phenotype. linA gene was
      found in 91 (20%) strains as single gene or in combination with erm or msr genes,
      and vga gene was found in 19 (4.2%) strains. linA gene was found in 52% of iMLSB
      phenotype, in 26% of cMLSB phenotype and 13% of M phenotype while vga gene was
      found in 5.4% of iMLSB phenotype, in 12% of cMLSB phenotype and in 0.9% of M
      phenotype. The most common resistance gene among iMLSB and cMLSB phenotypes was
      ermC (32.6% and 42.7%, respectively), followed by ermC + linA gene combination
      (31.5% and 14.5%, respectively). The most frequent gene combination was msrA and
      msrB in M phenotype (34.8%) and it was followed by a combination of msrA + msrB +
      linA genes (19.1%). None of the strains revealed presence of vgb, vat and vatB
      genes. There were no previous reports about the rarely detected resistance genes
      against MLSB antibiotics in our country. This was the first study which reported
      the frequency of linA, vga, vgb, vat and vatB genes in MLSB resistant CNS. In
      conclusion, since linA and vga genes were detected in high frequency in MLSB
      resistant CNS in this study, it was thought that the investigation of these genes
      should be included in the further related epidemiologic gene research.

PMID- 22639307
TI  - [The prevalence of antiseptic resistance genes (qacA/B and smr) and antibiotic
      resistance in clinical Staphylococcus aureus strains].
AB  - Staphylococcus aureus is an organism of major medical importance, leading to skin
      and soft tissue infections, bacteremia, and endocarditis. S.aureus isolates are
      becoming increasingly resistant to numerous antimicrobial agents including
      antiseptics and disinfectants. Quaternary ammonium compounds are disinfectants
      that play an important role in the control of nosocomial infections. Presence of
      genes conferring resistance to quaternary ammonium compounds is widely
      distributed among clinical staphylococci isolated from certain areas of the
      world. In this present study, we aimed to study the prevalence of antiseptic
      resistance genes (qac A/B, smr) and antibiotic resistance in clinical S.aureus
      strains, and also to detect the possible relationship between antiseptic and
      antibiotic resistance. For this purpose, the presence of qac A/B and smr genes in
      50 methicillin-susceptible S.aureus (MSSA) and 50 methicillin-resistant S.aureus
      (MRSA) clinical isolates (78 abscess, 13 blood, 3 sputum, 3 tracheal aspirate, 2
      nostril swab, 1 urine) was detected by using multiplex polymerase chain reaction.
      The susceptibility of S.aureus strains to different antibiotics (cefoxitin,
      erythromycin, clindamycin, rifampin, tetracycline, ciprofloxacin, gentamicin,
      trimethoprim-sulfamethoxazole, vancomycin, teicoplanin) was determined by disk
      diffusion method according to the recommendation of Clinical Laboratory Standards
      Institute (CLSI). smr genes were found in 18 (36%) of 50 MRSA and qacA/B genes in
      2 (4%) of 50 MSSA strains. Presence of smr gene only in MRSA strains in
      comparison to MSSA strains was found to be statistically significant (p< 0.001).
      The rates of antibiotic resistance in S.aureus strains were as follows;
      gentamicin 89%, tetracycline 57%, rifampin and ciprofloxacin 46%, and macrolides
      (erythromycin and clindamycin) 32%. No resistance was detected against
      trimethoprim-sulfamethoxazole, vancomycin and teicoplanin. On the other hand,
      presence of inducible macrolid-lincosamide-streptogramin B (iMLSB) resistance
      phenotype in 8 (44.5%) out of 18 smr positive strains compared to 2 (6.25%) out
      of 32 smr negative strains was statistically significant (p< 0.001). We concluded
      that smr genes were detected to be more prevalent than qacA/B genes in our
      clinical S.aureus isolates. smr genes were found only in MRSA strains whereas low
      number of qacA/B genes were found only in MSSA strains. Presence of smr genes
      concomitantly with iMLSB type resistance in MRSA strains was recorded to be
      interesting. We believe that data of this preliminary study about antiseptic and
      antibiotic cross resistance would be useful for the future related studies.

PMID- 22639308
TI  - [Evaluation of penicillin-binding protein genotypes in penicillin susceptible and
      resistant Streptococcus pneumoniae isolates].
AB  - Penicillin-binding proteins (PBPs) are the natural targets of beta-lactam
      antibiotics and mutations in pbp1a, pbp2b, and pbp2x genes, which encode PBPs,
      are responsible for resistance to beta-lactams in Streptococcus pneumoniae. In
      the present study, we intended to determine how often the common mutation
      patterns occurred within the pbp1a, pbp2b, and pbp2x PBP gene regions and
      evaluate the PBP genotype mutations which were associated with penicillin
      resistance in several penicillin-susceptible and - resistant S.pneumoniae
      isolates in Mersin, Turkey. A total of 62 S.pneumoniae strains isolated from
      different clinical specimens (32 nasopharyngeal swab, 16 sputum, 3 blood, 3
      wound, 2 cerebrospinal fluids and one of each urine, abscess, bronchoalveolar
      lavage, conjunctival swab, tracheal aspirate, middle ear effusion) were included
      in the study. Penicillin susceptibilities of the isolates were searched by disc
      diffusion and E-test methods, and 23 of them were identified as susceptible, 31
      were intermediate susceptible, and eight were resistant to penicillin. A rapid
      DNA extraction procedure was performed for the isolation of nucleic acids from
      the strains. Distribution of PBP gene mutations in pbp1a, pbp2b, and pbp2x gene
      regions related to penicillin resistance was determined by using a wild-type
      specific polymerase chain reaction (PCR) based technique. PBP gene alterations of
      those isolates were also evaluated in relation to penicillin susceptibility and
      resistance patterns. Twenty two (95.7%) of 23 penicillin-susceptible S.pneumoniae
      isolates exhibited no mutation in the three PBP genes (pbp1a, pbp2x, and pbp 2b),
      while 1 (4.3%) of these harbored mutations in all of the three PBP genes. The
      penicillin-intermediate susceptible S.pneumoniae isolates exhibited various
      combinations of mutations. One (3.2%) of 31 penicillin-intermediate susceptible
      isolates exhibited no mutation in the three PBP genes, while 22 (71%) of them
      yielded mutations in all of the three PBP genes. The remaining 8 (25.8%) isolates
      harbored mutations for dual PBP genes (in five strains pbp1a and pbp2b; in two
      strains pbp2x and pbp2b; in one strain pbp1a and pbp2x). Seven (87.5%) out of
      eight penicillin-resistant S.pneumoniae isolates (MIC >= 2 ug/ml) revealed
      mutations in all of the three PBP genes and the other penicillin-resistant
      isolates exhibited no mutation in the PBP genes. The present study supplied
      important data on the frequency of different patterns of mutations occurring at
      various regions of PBP genes related to penicillin resistance in S.pneumoniae
      isolates in our restricted region. The results supported the notion that
      penicillin resistance in S.pneumoniae was mainly attributed to alterations in
      pbp1a, pbp2x, and pbp2b gene regions and wild-type sequence specific PCR could be
      applied to characterize genotypic background of penicillin resistance in
      S.pneumoniae strains.

PMID- 22639309
TI  - [Genotyping of Mycobacterium tuberculosis strains isolated from pulmonary
      tuberculosis patients in Cukurova Region, Turkey by spoligotyping and MIRU-VNTR
      methods].
AB  - More rapid, and specific molecular diagnostic methods are required to understand
      the epidemiology of tuberculosis in the population and to establish effective
      control measures. Molecular epidemiologic studies about Mycobacterium
      tuberculosis are yet limited in Turkey. Cukurova (Eastern Mediterranean part of
      Turkey) region is of special importance in terms of tuberculosis epidemiology due
      to its neighbourhood countries and relatively high number of immigrants to that
      area. This study was aimed to determine the genotypic characteristics of
      M.tuberculosis strains isolated from pulmonary tuberculosis patients in Cukurova
      region, by spoligotyping and 12 loci MIRU-VNTR (Mycobacterial Interspersed
      Repetitive Unit- Variable Number Tandem Repeats) methods. A total of 467
      M.tuberculosis strains isolated from patients with pulmonary tuberculosis
      admitted to 20 hospital/dispansery in seven different provinces (Adana, Mersin,
      Osmaniye, Antakya, Gaziantep, Sanliurfa, Kahramanmaras) at Cukurova region
      between January 2007-June 2010, were included to the study. Genotypic
      identification was done by spoligotyping and 12 loci MIRU-VNTR methods.
      M.tuberculosis complex strains were isolated from different samples (sputum,
      bronchoalveolar lavage and biopsy material) by MGIT 960-TB (BD Diagnostics, USA)
      liquid culture method in Regional Tuberculosis Laboratory. Spoligotyping analysis
      revealed that 443 (94.9%) of the strains were clustered in 21 groups while 24
      (5.1%) of the isolates were described as orphan strains according to SpolDB4
      database. The most common families were T1 genotype seen in 239 (51.9%) strains
      and LAM7 TUR genotype seen in 54 (11.5%) strains. Six (1.3%) strains isolated
      from one province were multidrug resistant strains and belonged to Beijing
      family. Combination of spoligotyping with 12- locus MIRU-VNTR divided the T1
      family into 7 clusters of which members ranged from 2-158. Twenty one isolates
      showed unique pattern. According to this study, T1 family is the most common
      genotype among M.tuberculosis strains in Cukurova, Turkey and the prevalence of
      M.tuberculosis Beijing strains was 1.3%, detected only in one province
      (Sanliurfa). Active surveillance studies are necessary to follow the regional
      dissemination of M.tuberculosis genotypes and establish effective precautions to
      prevent the spread of especially drug resistant strains.

PMID- 22639310
TI  - [Detection of Bordetella pertussis infection by culture, real-time polymerase
      chain reaction and serologic tests among children with prolonged cough].
AB  - Pertussis is a respiratory infection caused by Bordetella pertussis. It attacks
      all age groups. It has significantly higher mortality and morbidity among
      newborns and children. Adolescents and adults with symptomatic but unrecognized
      pertussis are often the source of the infection for pediatric cases. Therefore,
      it is suggested to perform laboratory diagnostic tests for B.pertussis infection
      in children and adolescents with prolonged cough of more than two weeks. In this
      study, it was aimed to identify B.pertussis infection by culture, real-time
      polymerase chain reaction (Rt-PCR) and serological methods among children with
      prolonged cough. Nasopharyngeal swab samples were obtained from 51 children (19
      female, 32 male; age between 2 months-14 years; median age: 7.0), who attended
      the outpatient clinic of Ege University Medical Faculty Department of Pediatrics,
      Izmir, Turkey with prolonged cough (>= 14 days) during December 2009-August 2010.
      While pertussis vaccination had been completed in 48 (94%) of the cases, three
      cases had not been vaccinated. Previous antibiotic treatment was reported for 38
      (75%) of the cases. Cultivation was done by using 7% horse blood and charcoal
      containing Bordetella Agar (Becton Dickinson, Germany) and Rt-PCR targeting IS481
      sequence (Roche Applied Science, Germany) was used to detect B.pertussis. In
      addition, in house ELISA was performed to detect titers of anti-pertussis toxin
      (anti-PT) IgG and anti-filamentous hemagglutinin (anti-FHA) IgG antibodies in
      paired sera collected in 2-4 week intervals. Fourfold titer increase of
      antibodies or anti-PT IgG levels of at least 100 EU/ml in one serum were
      evaluated as serological confirmation of B.pertussis infection. In our study,
      B.pertussis was isolated from one nasopharyngeal swab samples culture among the
      51 patients, and IS481 Rt-PCR yielded positive results for B.pertussis in 6
      (11.8%) samples. Nine (17.6%) patients were diagnosed as B.pertussis infection by
      serological tests. Totally 12 patients were evaluated as positive using at least
      one method. Among them only one had positive results with three of the tests used
      and two were positive with IS481 Rt-PCR assay and serologic tests. Three patients
      were found positive with only IS481 Rt-PCR and six were identified only with
      serologic diagnosis. In this study, 23.5% (12/51) of children with persistant
      cough were evaluated as having B.pertussis infection. The age range of these
      cases (5 female, 7 male) was 2 months-11 years and one case had not been
      vaccinated at all while four cases had not completed the vaccination schedule. It
      was concluded that since B.pertussis can be detected as the etiologic agent of
      persistant cough in a significant number of children by culture, PCR and
      serologic tests, diagnostic tests must be applied to evaluate B.pertussis
      infection. However, standardized serological methods and PCR protocols are needed
      for accurate and reliable diagnosis.

PMID- 22639311
TI  - [Tularemia in Konya region, Turkey].
AB  - Tularemia is a zoonotic infection caused by Francisella tularensis. In the recent
      years tularemia has become a re-emerging infection in Turkey with epidemics and
      also sporadic cases. Transmission occurs most often through consumption of
      contaminated water and food, direct contact with animals and insect/ tick bites.
      In this study, we evaluated clinical features and laboratory findings of 35
      tularemia cases diagnosed during two outbreaks that occurred in two different
      villages during two different periods in Konya (located in Central Anatolia),
      Turkey and five sporadic cases. In both outbreaks, first (index) cases were
      admitted to our outpatient clinic with the complaints of cervical lympadenopathy.
      After diagnosis of tularemia, an organized team visited the villages to search if
      more cases existed. For microbiological diagnosis, blood, throat and tonsil swabs
      and lymph node aspirate specimens were collected from the suspected cases.
      Diagnostic tests (culture, serology, molecular methods) for tularemia were
      performed in reference center, Refik Saydam National Public Health Agency.
      Drinking and potable water samples from those villages were also collected by
      provincial health authorities. The cases (n= 14) that belonged to the first
      epidemics were detected in February 2010 and cases (n= 21) of the second
      epidemics in November- December 2010; five cases were followed as sporadic. The
      mean age of the 40 patients (25 females, 15 males) was 37.6 (age range: 5-80
      years; five of them were pediatric group) years. The most common complaints of
      patients were cervical mass (90%), sore throat (63%), chills (60%) and fever
      (58%). The most frequently detected clinical findings were enlarged lymph nodes
      (n= 34, 85%), followed by tonsillitis (20%), skin lesions (15%) and
      conjunctivitis (8%). Most of the patients (82.5%) had been misdignosed as acute
      tonsillitis, suppurative lymphadenitis, tuberculous lymphadenitis and
      brucellosis, before their admission to our hospital and treated with beta-lactam
      antibiotics. Demographic analysis of the cases revealed that 68% of them lived in
      the rural area, 75% had rodents at home, 46% used natural water supplies, 53% fed
      animals, 15% had contact with game animals and 5% had contact with ticks.
      Clinical samples from the patients were found culture negative for F.tularensis.
      The diagnosis of the cases was based on the presence of specific F.tularensis
      antibodies between 1/160-1/1280 titers obtained by microagglutination test.
      Additionally F.tularensis DNA was demonstrated in three lymph node aspirate
      samples by polymerase chain reaction (PCR). Water samples were found negative
      both by culture and PCR assays. However, it was detected that there were problems
      in the chlorination of water supplies in the two villages where epidemics were
      seen. All the patients were treated with streptomycin (2 x 1 g, intramuscular, 10
      days), and surgical intervention was performed for the patients (n= 12) with
      extremely large lymph nodes and suppuration. Erythema nodosum developed in two
      patients following the end of treatment. Death or serious complications such as
      pneumonia or meningitis were not detected. In conclusion, tularemia should be
      considered in patients presenting with cervical lymphadenopathy, sore throat,
      fever and unresponsive to previous treatment with beta-lactam antibiotics. For
      the management of the disease, healthcare personnel and the community should be
      educated concerning the risk factors and precautions for tularemia.

PMID- 22639312
TI  - [The effectiveness of hand hygiene products on MRSA colonization of health care
      workers by using CHROMagar MRSA].
AB  - The aims of this study were; to investigate the hand hygiene compliance of the
      health care workers (HCWs) during their routine patient care, to determine the
      methicillin-resistant Staphylococcus aureus (MRSA) hand colonization of the HCWs,
      to investigate the effect of different hand hygiene products on MRSA colonization
      and to evaluate the effectiveness of chromogenic agar for detecting MRSA. HCWs
      were investigated during their routine patient care and hand cultures were taken
      before and after hand wash/hygiene. Two different techniques were used to obtain
      the hand cultures: fingertip method (CHROMagar MRSA containing HygiSlide); and
      direct swab method and then inoculation to CHROMagar MRSA media. MRSA strains
      grown on those cultures were confirmed with conventional methods. A total of 100
      HCWs (of them 61 were female; mean age: 32.7 +/- 5.2 years; age range: 25-51
      years) involving physicians (n= 33), nurses (n= 38) and health care assistants
      (n= 29), were included in the study. MRSA was detected in 39% and 11% before hand
      hygiene and in 13% and 6% after hand hygiene, with HygiSlide CHROMagar media and
      with CHROMagar in plate media, respectively. No difference were found regarding
      clinics, occupations, or the type of patient handling in those HCWs who were
      positive (n= 13) for MRSA colonization following hand hygiene, and those who were
      negative (n= 26). However, the type of the hand hygiene product used exhibited a
      statistical difference. None of the seven HCWs who used alcohol based hand rub
      revealed growth in the second culture while 10 of 19 (53%) HCWs who used soap and
      three of 13 (23%) HCWs who used chlorhexidine were still colonized with MRSA. In
      terms of reduction in the MRSA counts, the most effective one was the alcohol
      based hand rub while the soap was the least, since seven of 19 (37%) HCWs who
      used soap showed no reduction at all in the MRSA counts. A high ratio of hand
      colonization with MRSA was detected in our hospital staff (39%). It was shown
      that the colonization could be reduced significantly (with a rate of 66%) with
      hand hygiene. Alcohol based hand rub was found to be the most effective method in
      hand hygiene. The fingertip technique was found to be superior to inoculation to
      plate media for obtaining hand cultures and CHROMagar MRSA media was found to be
      rapid, effective and practical for detecting the MRSA hand colonization.

PMID- 22639313
TI  - [Seroprevalence of Borrelia burgdorferi and tick-borne encephalitis virus in a
      rural area of Samsun, Turkey].
AB  - Lyme disease or lyme borreliosis is a zoonosis caused by Borrelia burgdorferi
      transmitted by ticks, especially Ixodes species. Lyme borreliosis is a multi
      systemic disease that invades the skin, musculoskeletal, cardiovascular and
      central nervous systems. Tick-borne encephalitis (TBE) is an important arboviral
      infection caused by tick-borne encephalitis virus (TBEV). The central nervous
      system is affected and the disease most often manifests as meningitis,
      encephalitis or meningoencephalitis. Previous studies have shown that
      B.burgdorferi and TBEV can be transmitted by the same tick species (Ixodes
      ricinus). Although the geographic location and climate is similar to some south
      eastern European countries where lyme borreliosis and TBE have been reported, the
      incidence and prevalence of these diseases in Turkey still remain unclear. The
      aim of this study was to determine the seroprevelance of B.burgdorferi and TBEV
      in healthy population in Tekkekoy (41 degrees  8-13' North; 36 degrees  24-31'
      East), a district of Samsun province, Turkey with evidence of tick-borne disease
      and to explore the possible correlations of life styles of healthy individuals
      and prevelance. The cross-sectional study population included 419 people selected
      using a random proportional sampling method. All participants were asked at
      interview to complete a questionnaire and peripheral blood samples were
      collected. From the blood samples, B.burgdorferi IgG and IgM antibodies were
      evaluated using commercial ELISA (Euroimmun, Germany) and confirmed with Western
      blot (WB, Euroimmun, Germany). ELISA method was also used to asses IgM and IgG
      antibodies against TBEV, and neutralization test was used for confirmation. Of
      the 419 samples, 17 (4%) were positive for B.burgdorferi IgG by ELISA, however 14
      (14/419; 3.3%) of them were confirmed by WB. B.burgdorferi seropositivity was
      higher among people living in rural areas, at an altitude of >= 400 meters and in
      locations ecologically suitable for wild boar and rabbits; seropositivity was
      also seen to be higher among dog owners (p= 0.001, p= 0.001, p= 0.001, p= 0.001,
      p= 0.018, respectively). For TBEV, two samples yielded IgG positive, and one IgM
      positive results by ELISA, however none of them were confirmed by neutralization
      assay. Nevertheless, one of those three TBEV ELISA positive samples, was found
      positive for West Nile virus specific antibodies with neutralization test. The
      results of this study emphasized the presence of tick-borne diseases in that
      specific region, and in this regard the need for public health interventions has
      been demonstrated.

PMID- 22639314
TI  - [25S intron analysis followed by restriction enzyme digestion performed for
      genotyping Candida albicans isolates].
AB  - Candida albicans is the most frequently encountered fungal pathogen especially in
      the immunocompromised hosts. Genotyping clinical microbial isolates is important
      for obtaining epidemiological data and for establishing appropriate infection
      control strategies in the hospital setting. 25S intron analysis is an easy and
      reliable method used for genotyping C.albicans strains. As it has a low
      discriminatory power, its use is limited in epidemiological studies. In this
      study, our aim was to genotype clinical C.albicans isolates by using 25S intron
      analysis followed by restriction enzyme digestion in order to develop a more
      discriminative genotyping system for C.albicans. A total of 260 clinical
      C.albicans strains isolated from various infection sites (121 blood, 69 sputum,
      36 vaginal discharge, 26 wound, 8 urine samples) were genotyped by 25S intron
      analysis, and all the products obtained by polymerase chain reaction (PCR) were
      digested with HaeIII restriction enzyme. Discriminatory power of each method was
      calculated. Among the isolates 184 (70.8%) were classified as genotype A, 42
      (16.2%) as genotype B, and 34 (13%) as genotype C by 25S intron analysis.
      Discriminatory power of the method was calculated as 0.46. HaeIII restriction of
      genotype A, B and C isolates produced ten, one, and five restriction patterns
      (genotypes), respectively. By the addition of restriction enzyme analysis, the
      number of genotypes obtained was increased to 16, and the discriminatory power of
      the method to 0.79. Combining different genotyping methods increases the
      discriminatory power by increasing the number of genotypes obtained. However,
      there is also a risk to split certain strains in different genotypes by the
      different methods used and this makes the genotypic evaluation more difficult. On
      the other hand, combining 25S intron analysis with restriction enzyme analysis
      increases the discriminatory power without introducing a totally different
      method, and makes the method more suitable for epidemiological purposes and for
      genotyping clinical isolates. Different enzymes instead of HaeIII should be
      tested to evaluate the effect on the discriminatory power. In order to evaluate
      the relationship between the genotypes obtained by this method and parameters
      such as patient characteristics, clinical data, and antifungal susceptibilities,
      more sophisticated studies can be performed.

PMID- 22639315
TI  - [Investigation of mold fungi in air samples of elementary schools and evaluation
      of allergen-specific IgE levels in students' sera].
AB  - Atmospheric fungal spores play important role in allergic reactions in atopic
      individuals. Monitorization of those spores found in the environment of atopic
      cases is crucial for the choice of the antigens that will be included in allergen
      screening procedures and precautions to be taken against mold-originated health
      problems. Since most of the people spend plenty of time indoors in recent years,
      the effects of exposure to indoor air fungi on human health have gained
      importance. This study was aimed to investigate the indoor air mold distribution
      of elementary schools in Denizli province (located in west Anatolia, Turkey) and
      to compare the allergen-specific IgE levels of children against the most
      frequently detected mold genus. A questionnaire (MM080) was distributed to the
      4967 students (6-8 year-old) attending first and second degrees of 16 different
      elementary schools with scattered locations in city center. This questionnaire
      form included the questions related to the general information about the child,
      school environment, allergic complaints since last year, home environment and
      nutrition. Response rate to the questionnaire was 51.6% (2565/4967). Air samples
      were collected from 18 classrooms in March 2009, during which high rates of
      allergic symptoms were observed according to the questionnaire results. Mold
      fungi belonging to 10 different genera (Penicillium spp. 46%; Aspergillus spp.
      18%; Cladosporium spp. 17%; Alternaria spp. 15%; Drechslera spp. 1%;
      Chrysosporium, Fusarium, Conidiobolus and Cladothecium species 0.5%; unidentified
      1%) were isolated from indoor air of classrooms. Since the most frequently
      detected mold was Penicillium spp. (46%), the 48 children with atopic symptoms
      were called to the hospital for the determination of total IgE and Penicillium
      specific IgE in their sera. Twenty two students accepted the invitation and serum
      total IgE (Immulite 2000; Diagnostic Product Corporation, USA) and allergen
      specific IgE (Penicillium brevicompactum, Penicillium camemberti, Penicillium
      chrysogenum, Penicillium commune, Penicillium expansum, Penicillium frequentans,
      Penicillium glaucum, Penicillium notatum, Penicillium roqueforti ve Penicillium
      viridicatum) (RIDASCREEN; R-Biopharm AG, Germany) levels were determined in those
      children. Total IgE levels above reference ranges were detected in 41% (9/22) of
      the screened sera samples. P.roqueforti, P.commune and P.camemberti antibodies
      were higher (Odds ratio as 5.50, 4.0 and 3.75, respectively) in sera with high
      total IgE levels. No independent variables were determined between individual
      and/or environmental factors and Penicillium-specific IgE antibodies. It was
      concluded that those three strains should be chosen as antigens for mold allergy
      screening tests which will be performed among atopic cases in our region. In
      conclusion it should be kept in mind that molds have a possible role in the
      development of allergic symptoms, however, they are not the sole determining
      factor in this process. In the investigation of the allergic diseases
      environmental factors should be considered and standardized methods should be
      applied.

PMID- 22639316
TI  - [Phenotypic and genotypic traits of vancomycin-resistant enterococci in a public
      hospital: the first vanB-positive Enterococcus faecium isolates].
AB  - Thirty eight vancomycin resistant enterococci (VRE) were isolated in one year
      surveillance study for hospital infection control programme in a state hospital
      in Ankara, Turkey. All isolates were identified as Enterococcus faecium by VITEK2
      system (bioMerieux, France). Vancomycin and teicoplanin resistant 30 strains were
      defined as vanA phenotype while vancomycin-resistant teicoplanin-susceptible
      eight strains were defined as vanB phenotype. vanA genes were found in 30 strains
      while vanB genes were found in five strains by using PCR method. Those five
      strains were the first vanB positive E.faecium strains in our country. VRE
      strains revealed six different band patterns by PFGE, while six isolates could
      not be classified. All isolates with vanB type resistance were found in the same
      cluster. Source of vanB positive strains was considered as the hemodialysis unit.
      When the previous national reports related to vancomycin-resistant enterococci
      were considered, this was the first report of vanB positive E.faecium isolates in
      our country. This emphasized that both the diversity of VRE and the isolation
      rate was increasing. In order to eliminate the spread of VRE, effective
      surveillance studies should be performed and protective measures should be
      established promptly.

PMID- 22639317
TI  - [Isolation and identification of Mycobacterium bovis and non-tuberculous
      mycobacteria in raw milk samples in Mersin province].
AB  - This study was aimed to isolate and identify Mycobacterium bovis and non
      tuberculous mycobacteria (NTM) species in raw milk samples from cattles and to
      compare the diagnostic performance of the methods used for that purpose. A total
      of 145 raw milk samples from cattles were collected from five villages in Mersin
      province (located on Mediterrenean region of Turkey) between April and June 2008.
      Presence of mycobacteria was investigated by Ehrlich Ziehl Neelsen (EZN) staining
      method, culture in Lowenstein- Jensen (LJ) medium and polymerase chain reaction
      (PCR). Only 1 (0.7%, 1/145) raw milk sample was found to be acid fast bacilli
      (AFB) positive with EZN staining. Eleven (7.6%) samples were positive by culture
      and mycobacterial DNA was detected in 6 (4.1%) samples by PCR. Mycobacterium was
      isolated from both creamy and pellet layer of a culture positive sample.
      Identification was carried out with conventional biochemical tests, PCR
      Restriction Fragment Length Polymorphisms (PCR-RFLP) and spoligotyping (spacer
      oligonucleotide typing) methods. One isolate was identified as Mycobacterium
      tuberculosis complex (MTC) and 11 isolates were identified as NTM out of 12
      isolates those were isolated from culture. According to PCR-RFLP analysis of
      these 11 NTM isolates, 6 (54.5%) were Mycobacterium genavense, 2 (18.2%) were
      Mycobacterium simiae, 2 (18.2%) were Mycobacterium szulgai and 1 (9.1%) was
      Mycobacterium fortuitum. MTC isolate was identified as M.bovis by spoligotyping.
      According to the results of our study, both pellet and creamy layers from raw
      milk samples should be cultured to selective LJ medium (without glycerol, with
      0.4% sodium pyruvate) to improve the chance of isolation and must be incubated
      for up to eight weeks. In our region, NTM were isolated in 6.9% and M.bovis in
      0.7% of the raw milk samples from cattles and this emphasized the risk of
      transmission of mycobacteria to man via direct contact or ingestion of
      unpasteurized milk products.

PMID- 22639318
TI  - [The rates of seropositivity and seroconversion of toxoplasma infection in
      pregnant women].
AB  - Infections caused by Toxoplasma gondii are frequently asymptomatic in healthy
      adults, however they may be serious in pregnant women and immunocompromised
      patients. The aims of this study were to investigate the rates of seropositivity
      and seroconversion in pregnant women and newborn cord blood samples, and to
      evaluate those data in the view of relation to lifestyle and nutrition. A total
      of 312 pregnant women (mean age: 28.1 +/- 5.2 years) who were admitted to and
      followed by gynecology clinics of Inonu University Medical School Hospital,
      Malatya, Turkey were included in this observational and cross-sectional study.
      Anti-toxoplasma IgG and IgM antibodies in pregnants and newborn cord sera were
      screened by commercial ELISA and immunofluorescence antibody (BioTek; USA)
      methods. A total of 312 sera from pregnant women and 312 cord blood samples
      during delivery were collected. IgG seropositivity rate in pregnants was found as
      37.5% (117/312), seroconversion was not determined in restrained pregnants and
      T.gondii IgM was found negative in all pregnants. Also in all newborns IgM was
      negative and IgG seropositivity was determined as 33.3% (104/312) in cord blood.
      There was a statistically significant relationship between IgG seropositivity and
      raw meat consumption (p< 0.001) and being engaged in agriculture (p< 0.005). It
      was concluded that toxoplasma antibodies should routinely be searched on the
      first visit of the pregnants and the seronegative cases should be trained about
      the preventive measures related to toxoplasmosis. The follow-up of toxoplasma
      seronegative cases during pregnancy can be achieved by only detecting the IgM
      class antibodies and this will also reduce the cost of screen test.

PMID- 22639319
TI  - [A case of ventilator-associated pneumonia due to Pantoea agglomerans].
AB  - Pantoea species, which are the members of Enterobacteriaceae family are gram
      negative bacilli that are frequently found on many plants and in soil. They may
      lead to localized infections in healthy subjects and systemic infections in
      immunosuppressed patients. In this case report a ventilator-associated pneumoniae
      due to Pantoea agglomerans was presented. A 55 year-old male patient with chronic
      renal failure was hospitalized in intensive care unit following cardiopulmonary
      arrest. The patient developed fever (38.8 degrees C), had pulmonary infiltrations
      in chest X-ray and leucocytosis. Treatment with piperacillintazobactam was
      initiated upon diagnosis of nosocomial pneumoniae. Bacterial growth from the deep
      tracheal aspirate of the patient was identified as P.agglomerans by VITEK2
      automated system (bioMerieux, France) and the identification was confirmed by
      conventional microbiological methods. Since the strain was susceptible to the
      cephoperazon-sulbactam, tobramycin, tetracycline, gentamicin and levofloxacine,
      the treatment was changed to levofloxacine and cephoperazon-sulbactam and the
      patient improved. This case was presented to withdraw attention to rare
      opportunistic pathogens that may lead to nosocomial infections particularly in
      patients with underlying diseases.

PMID- 22639320
TI  - [Paradoxical radiologic progression despite appropriate anti-tuberculous
      therapy].
AB  - Clinical or radiological deterioration of tuberculosis despite appropriate anti
      tuberculous therapy is defined as paradoxical response. Since identification of
      paradoxical response presents difficulties, this issue is not only of medical
      importance but also of legal importance. In this report, a tuberculosis case who
      got worse paradoxically during the course of anti-tuberculous therapy, was
      presented. Human immunodeficiency virus (HIV)-negative 68-year-old male patient
      was admitted to the hospital with the complaints of cough, chest pain, and weight
      loss. Computed tomography of the chest revealed an irregular non-homogenous
      opacity involving the apical and posterior segments of superior lobe of the right
      lung. Since acid-fast bacilli were detected in the sputum sample, active
      pulmonary tuberculosis was diagnosed and four-drug regimen treatment (isoniazid
      300 mg/day, rifampicin 600 mg/day, pyrazinamide 2 g/day, etambutole 1.5 g/day)
      was initiated. At the end of the first month of therapy radiological lesions
      increased. There was no endobronchial lesion on bronchoscopy, and no acid-fast
      bacilli in bronchial lavage fluid. Therapy protocol was not changed, however
      radiological lesions regressed gradually. It was concluded that temporary
      deteriorations might occur in previous pulmonary infiltrates in patients who were
      under appropriate anti-tuberculous therapy. The gold standard for monitorization
      of anti-tuberculous therapy is microbiological methods rather than the
      radiological ones. Comorbid conditions, drug reactions, patient compliance and
      treatment failure are important parameters in the differential diagnosis. This
      case was presented to emphasize the importance of tuberculosis which is still
      prevalent in Turkey.

PMID- 22639321
TI  - [An opportunistic pathogen frequently isolated from immunocompromised patients:
      Burkholderia cepacia complex].
AB  - Burkholderia cepacia complex is a group of 17 closely related species. For a long
      time B.cepacia complex is believed to be only a plant pathogen but later it has
      emerged as an important opportunistic pathogen causing morbidity and mortality in
      hospitalized patients. B.cepacia complex particularly causes bacteraemia/sepsis,
      septic arthritis, osteomyelitis, meningitis, peritonitis, urinary and respiratory
      tract infections. Patients with cystic fibrosis or chronic granulomatous disease
      are predisposed to B.cepacia complex infections. B.cepacia complex can survive
      for a long period of time and can easily multiply in aqueous environments such as
      disinfectant agents and intravenous fluids used in hospitals. Patients may
      acquire B.cepacia complex either from the environment or through patient-to
      patient transmission. It has always been a tedious task for routine microbiology
      laboratory to identify B.cepacia complex. In these laboratories, the
      identification of B.cepacia complex isolates is generally performed using a
      combination of selective media, conventional biochemical analysis and/or
      commercial systems. Three media commonly used for isolation of B.cepacia complex
      are as follows: the Pseudomonas cepacia agar, the oxidation-fermentation based
      polymyxin bacitracin lactose agar, and more recently the B.cepacia selective
      agar. Members of the B.cepacia complex can be identified by available commercial
      tests, such as API 20NE, Phoenix, MicroScan or VITEK. Molecular techniques are
      useful for confirmation of phenotypic identification and discrimination beyond
      the species-level. B.cepacia complex is intrinsically resistant to antimicrobial
      agents such as aminoglycosides, first- and second-generation cephalosporins,
      antipseudomonal penicillins and polymyxins. B.cepacia complex bacteria often
      develop resistance to beta-lactams due to presence of inducible chromosomal beta
      lactamases and altered penicillin- binding proteins. Antibiotic efflux pumps in
      B.cepacia complex bacteria mediate resistance to chloramphenicol, trimethoprim
      and fluoroquinolones. Under antimicrobial pressure, resistance can quickly
      develop to all susceptible antimicrobials. In this review, the classification and
      microbiological features of B.cepacia complex, mechanisms of virulence and
      pathogenesis, epidemiological properties, clinical spectrum, laboratory
      diagnosis, antimicrobial resistance and treatment, prevention and control
      measures were summarized.

PMID- 22639322
TI  - [Use of molecular techniques in the diagnosis of pulmonary and extrapulmonary
      tuberculosis].
AB  - Tuberculosis, is a life-threatening infectious disease and one of the leading
      causes of mortality worldwide. It is a multisystemic disease, and involvement of
      lungs and pleura is seen in majority of patients. The global control of
      tuberculosis is impeded by the relatively low sensitive conventional diagnostic
      assays, especially for drug resistant strains. The current gold standard for
      tuberculosis diagnosis is the combination of culture and clinical diagnosis.
      Since conventional diagnostic assays require long time, are labor intensive and
      insufficient for species-level identification, new solutions for problems in
      routine diagnostic applications for tuberculosis are required. Implementation of
      reliable, highly specific and sensitive assays which were standardized for rapid
      diagnosis of Mycobacterium tuberculosis, is recommended by Centers for Disease
      Control and Prevention (CDC). Implementation of nucleic-acid amplification based
      tests (NATs) to support rapid diagnosis especially in reference laboratories or
      health-care clinical laboratories, which use the diagnostic algorithms denoted in
      CDC guidelines, meet American Thoracic Society class 2 and 3 standards and have
      smear positive sample counts >= 500 per year, is accepted as a logical and cost
      effective approach. Analysis of cost-effectiveness for NATs are also required for
      global TB management plans. All current meta-analysis on NAT for tuberculosis
      indicate that in-house assays display considerable variations in sensitivity and
      specificity and exhibit discrepancies with commercial NATs. Evaluations also
      notified that the specificity for NAT is usually higher than expected in
      laboratory diagnosis of both forms of tuberculosis, whereas sensitivity is very
      low with considerable inter-assay variations. In conclusion, it is thought that
      current NATs are not reliable as single assays for rapid tuberculosis diagnosis
      for routine testing and should not be used in screening, but they are valuable
      methods in supporting conventional assays for clinical follow-up of patients.
      This review article discusses the diagnostic value of molecular methods in the
      evaluation of pulmonary and extrapulmonary tuberculosis in the light of the
      current literature.

PMID- 22639323
TI  - [Differences of vacA alleles and cagA gene positivity of Helicobacter pylori
      strains isolated from two different countries: Turkey and Germany].
AB  - Helicobacter pylori strains isolated from different regions of the world or human
      ethnic groups exhibit some differences at certain loci. The aim of this study was
      to determine allelic differences of H.pylori strains isolated from two countries,
      Turkey and Germany. A total of 72 H.pylori isolates, of which 37 strains were
      from Kocaeli province of Turkey and 35 strains from Hamburg, Germany were
      included in this study. H.pylori strains had been isolated from gastric biopsies
      of the patients. Genomic DNA was extracted with phenol-chloroform-isoamyl alcohol
      procedure and vacA alleles and cagA regions were identified by polymerase chain
      reaction (PCR) using specific primer sets. The rates of cagA positivity in
      Kocaeli and Hamburg strains were found as 75.7% (28/37) and 71.4% (25/35),
      respectively. VacA s1a allele was predominant both in Turkey and Germany
      isolates. There were five vacA mosaicisms in Hamburg strains, including 14 for
      s1a/m1a (40%), nine for s1a/m2 (25.7%), eight for s2/m2 (17.1%), three for s1a/m1
      (8.5%) and three for s1b/m2 (8.5%). There were four vacA mosaicisms in Kocaeli
      strains, including 22 for s1a/m2 (59.4%), eight for s2/m2 (21.6%), four for
      s1a/m1a (10.8%), and three for s1a/m1 (8.1%). In this study, Hamburg and Kocaeli
      strains did not reveal significant differences regarding cagA status and vacA s1
      allele. Whereas vacA s1a/m1a, cagA(+) type was the most frequent in Hamburg
      strains and s1a/m2, cagA (+) type in Kocaeli strains.

PMID- 22639324
TI  - [Factors associated with mortality in Acinetobacter baumannii infected intensive
      care unit patients].
AB  - Acinetobacter baumannii can survive for prolonged periods in unsuitable
      environmental conditions and easily spread to patients in the hospital settings
      leading to healthcare-associated infections. Major risk factors for A.baumannii
      infections are mechanical ventilation, invasive procedures such as central venous
      catheter or urinary catheter and the use of broad-spectrum antibiotics. The
      mortality rates of nosocomial A.baumannii infections have been reported between
      50-60%, changing due to several factors. The aim of this study was to investigate
      the factors associated with mortality in intensive care unit (ICU) patients
      diagnosed as nosocomial A.baumannii infections. The demographical, clinical and
      microbiological data of the patients who were followed in ICUs between September
      2008 to March 2010 were evaluated retrospectively, and analyzed regarding the
      factors related to mortality. Blood, urine and tracheal aspirate samples were
      collected from suspected patients and cultivated on conventional agar media. The
      identification of the isolates and antibiotic susceptibilities were performed by
      using VITEK-2 (bioMerieux, USA) automated system. The patients with A.baumannii
      infections were grouped as "died" and "survived" cases, and the groups were
      compared according to following factors: age, gender, isolation day of bacteria
      in intensive care unit, type of clinical sample, implementation day of the
      central venous catheter, implementation of tracheotomy and/or intubation,
      operation, presence of diabetes mellitus, antibiotic use, day of hospitalization,
      day of mechanical ventilation and APACHE (Acute Physiology and Chronic Health
      Evaluation)-II score. A.baumannii infection was identified in 56 patients (29
      female, 27 male; mean age: 63 years) in the intensive care units during the study
      period, and the total mortality rate was estimated as 77% (43/56). The
      implementation of intubation, mechanical ventilation, high APACHE II score and
      recovery of bacteria from respiratory tract were found statistically significant
      for A.baumannii infections related mortality (p< 0.05 for each parameter). Our
      data showed that Acinetobacter infection in the respiratory tract, implementation
      of intubation, mechanical ventilation and high APACHE II scores were the major
      risk factors related to mortality.

PMID- 22639325
TI  - [A rare cause of pneumonia: Shewanella putrefaciens].
AB  - We read with interestingly the paper named "A Rare Cause of Pneumonia: Shewanella
      putrefaciens" presented by Durdu et al. published in Mikrobiyol Bul 2012; 46(1):
      117-21. S.putrefaciens is a gram-negative, facultative anaerobic and non
      fermentative rod that rarely causes infections in humans. First, the authors
      reported that antibotic sensitivity tests of S.putrefaciens in the presented case
      were performed by Kirby-Bauer disc diffusion method. However, there is no
      recommendation about the antibiotic susceptibility testing by disc diffusion test
      for this bacteria in Clinical and Laboratory Standards Institute (CLSI), European
      Committee on Antimicrobial Susceptibility Testing (EUCAST), and British Society
      for Antimicrobial Chemotherapy (BSAC) guidelines. According to CLSI criteria,
      antibiotic susceptibility tests for S.putrefaciens should be done by a method
      which detects minimal inhibitory concentration. Second, this paper reported that
      S.putrefaciens was sensitive to third generation cephalosporins and penicillins.
      Besides, the authors suggested that susceptibility of these bacteria to these
      antibiotics was helpful for the differential diagnosis of Pseudomonas aeruginosa
      and S.putrefaciens. However, in the literature, S.putrefaciens had been reported
      as resistant to penicillin. We thought that these additional information would be
      helpful in the future studies related to S.putrefaciens.

PMID- 22639326
TI  - Brief communication: Hand preference for bimanual and unimanual feeding in
      captive gorillas: extension in a second colony of apes.
AB  - Right-hand dominance is widely considered to be a uniquely human trait. Whether
      nonhuman primates exhibit similar population-level hand preferences remains a
      topic of considerable debate. Despite extensive research focusing on laterality
      in nonhuman primates, our interpretation of these studies is limited due to
      methodological issues including the lack of a common measure of hand preference
      and the use of tasks that may not be reliable indicators of handedness. The use
      of consistent methods between studies is necessary to enable comparisons within
      and between species and allow for more general conclusions to be drawn from these
      results. The present study replicates methods used in recent research reporting
      population-level right-handedness in captive gorillas (Meguerditchian et
      al.,2010). Observational data were collected on hand preference for unimanual and
      bimanual feeding in 14 captive western lowland gorillas (Gorilla gorilla
      gorilla). Individual-level preferences were found, primarily for bimanual
      feeding; however, the data reveal no group-level directional bias (contra
      Meguerditchian et al.). Like the study by Meguerditchian et al. (2010), though,
      bimanual feeding revealed significantly stronger hand preferences than unimanual
      reaching, and age, sex, group membership, or rearing history had no effect on
      hand preference. Finally, variations in diet and corresponding grip type between
      studies suggest that hand preferences may vary across bimanual tasks depending on
      grip morphology. This study aims to contribute to our existing knowledge of
      primate laterality by increasing the number of individuals investigated using
      methods that allow for comparisons with similar research.

PMID- 22639327
TI  - In memoriam: Rose Grobstein (1917-2011).

PMID- 22639329
TI  - Complications in brief: Osteotomy for lower extremity malalignment.
AB  - When performing an osteotomy for lower extremity malalignment, several
      complications can occur. These can include introducing iatrogenic malalignment,
      intraoperative fracture or vascular injury, postoperative recurrence of
      deformity, patella baja, and challenges when performing subsequent total knee
      replacement in the future. Likewise, a poor functional result can occur secondary
      to poor preoperative planning and patient selection. In this article, we review
      the complications that can occur as a result of errors made before, during, and
      after surgery. This article pertains to opening and closing wedge osteotomies of
      the distal femur and proximal tibia.

PMID- 22639328
TI  - Prenatal treatment of congenital adrenal hyperplasia-not standard of care.
AB  - Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency is
      a common autosomal recessive disorder due to mutations in the CYP21A2 gene. Since
      genetic counselors play a crucial role in educating families about inherited
      disorders, they need to have thorough knowledge regarding the pathophysiology of
      CAH especially the effects on the fetus, the complex genetics of this disorder,
      and the controversies surrounding experimental prenatal dexamethasone treatment.
      Affected female fetuses may have varying degree of virilization of the external
      genitalia. Starting in the 1980's, supraphysiologic glucocorticoid treatment was
      used to decrease the virilization of the external genitalia of affected female
      fetuses. However, recent clinical observations, animal studies and greater
      awareness of the details of human fetal adrenal physiology raise concerns
      regarding the safety of this prenatal treatment. We review the pathophysiology of
      CAH, the safety and ethical considerations of prenatal dexamethasone treatment
      and the views of multiple medical societies that conclude that this experimental
      therapy should only be done in prospective trials approved by ethical review
      boards.

PMID- 22639330
TI  - Is a cementless dual mobility socket in primary THA a reasonable option?
AB  - BACKGROUND: Dislocation after THA continues to be relatively common. Dual
      mobility sockets have been associated with low dislocation rates, but it remains
      unclear whether their use in primary THA would not introduce additional
      complications. QUESTIONS/PURPOSES: We therefore asked whether a current
      cementless dual mobility socket (1) reduced the dislocation rate after primary
      THA, (2) provided a pain-free and mobile hip, and (3) provided durable
      radiographic fixation of the acetabular component without any unique modes of
      failure. METHODS: We retrospectively reviewed 168 patients who underwent primary
      THA using a dual mobility socket between January 2000 and June 2002. The average
      age at surgery was 67 years. We assessed the rate of dislocation, hip function,
      and acetabular fixation on serial radiographs. Of the 168 patients, 119 (71%) had
      clinical and radiographic evaluation at a minimum of 5 years (mean, 6 years;
      range, 5-8 years). RESULTS: A long-neck option left the base of the Morse taper
      uncovered in 53 hips. Four patients underwent revision for dislocation between
      the femoral head and the mobile insert (intraprosthetic dislocation) at a mean 6
      years; all four revisions occurred among the 53 hips with an incompletely covered
      Morse taper. CONCLUSIONS: A current cementless dual mobility socket was
      associated with a pain-free and mobile hip and durable acetabular fixation
      without dislocations if the long-neck option was not used. However,
      intraprosthetic dislocation related to contact at the femoral neck to mobile
      insert articulation required revision in four hips. Surgeons should be aware of
      this specific complication. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 22639331
TI  - Value of T2-weighted magnetic resonance imaging in the assessment of wall
      inflammation and fibrosis in Crohn's disease.
AB  - This review focuses specifically on the diagnostic value of T2-weighted imaging
      in the assessment of Crohn's disease (CD) inflammation. In general, T2-weighted
      imaging has been less extensively investigated than T1-weighted gadolinium
      enhanced imaging, even if it may offer similar information on disease activity.
      Furthermore, T2-weighted imaging allows CD characterization, which is crucial in
      the management of the disease when differentiating intestinal edema from
      fibrosis. Technical aspects, morphological findings and signs of active
      intestinal inflammation and fibrosis detectable on T2-weighted images will be
      reviewed and shown. Correlation between T2-weighted imaging findings, clinical
      activity indexes and histopathology features will be discussed. Since T2-weighted
      imaging is essential in the evaluation of CD activity, it should always
      complement with T1-weighted imaging, although it could also be used alone in the
      assessment of CD.

PMID- 22639332
TI  - Porous Ni@Pt core-shell nanotube array electrocatalyst with high activity and
      stability for methanol oxidation.
AB  - Bimetallic core-shell nanostructures are emerging as more important materials
      than monometallic nanostructures, and have much more interesting potential
      applications in various fields, including catalysis and electronics. In this
      work, we demonstrate the facile synthesis of core-shell nanotube array catalysts
      consisting of Pt thin layers as the shells and Ni nanotubes as the cores. The
      porous Ni@Pt core-shell nanotube arrays were fabricated by ZnO nanorod-array
      template-assisted electrodeposition, and they represent a new class of
      nanostructures with a high electrochemically active surface area of 50.08 m(2) 
      (g Pt)(-1), which is close to the value of 59.44 m(2)  (g Pt)(-1) for commercial
      Pt/C catalysts. The porous Ni@Pt core-shell nanotube arrays also show markedly
      enhanced electrocatalytic activity and stability for methanol oxidation compared
      with the commercial Pt/C catalysts. The attractive performances exhibited by
      these prepared porous Ni@Pt core-shell nanotube arrays make them promising
      candidates as future high-performance catalysts for methanol electrooxidation.
      The facile method described herein is suitable for large-scale, low-cost
      production, and significantly lowers the Pt loading, and thus, the cost of the
      catalysts.

PMID- 22639333
TI  - Breaking bad news in China--the dilemma of patients' autonomy and traditional
      norms. A first communication skills training for Chinese oncologists and
      caretakers.
AB  - OBJECTIVE: Current practice of breaking bad news in China involves disclosure of
      information first to family members who then decide whether the patient should
      receive this information. Recently, however, patients' right to be informed has
      been regulated by law. This represents a dilemma for oncologists who now have to
      balance traditional practice with new legal requirements. A communication skills
      training (CST) was developed for Chinese practice. It addresses this issue and
      may help participants find individual solutions within these conflicting
      requirements. METHODS: A first CST about breaking bad news took place at the
      Beijing Cancer Hospital, China, with 31 participants. We (i) assessed current
      practice, (ii) evaluated the workshop and (iii) self-assessed performance ratings
      about breaking bad news before and after the workshop with the help of
      questionnaires. RESULTS: (i) Participants stated that in most cases (78%), they
      inform family members first. Contrary to this practice, participants think that
      about 75% of patients would like to be informed first, independent of family.
      (ii) Overall, the workshop received a very good rating (M = 1.2; scale between 1
      and 6). (iii) After the workshop, the participants rated their performance
      significantly higher in all areas, for example, talking about diagnosis,
      prognosis and death with the patient and the family. CONCLUSIONS: The CST showed
      high acceptance and led to significantly improved performance ratings of
      participating physicians in many areas. It helped participants deal with
      conflicting demands. For future trainings, further socio-cultural adaptations are
      needed. Obvious conflicts still exist and need to be resolved.

PMID- 22639334
TI  - Enantioselective rhodium-catalyzed addition of potassium alkenyltrifluoroborates
      to cyclic imines.

PMID- 22639335
TI  - Evaluation of labyrinthine fistula by MR cisternography.
AB  - Sensorineural hearing loss (SNHL) can develop after trauma and determination of
      its etiology is crucial for treatment planning. Computed tomography (CT) is the
      first-line imaging method in evaluation of trauma victims; however, its value is
      limited in visualization of perilymphatic fistula or in assessment of cochlear
      implant candidates. Herein, we present imaging findings of a patient with
      traumatic bilateral transverse fractures of temporal bones and resultant SNHL.
      This patient had a fistula between inner ear and subarachnoid space which was
      detected at non-contrast-enhanced MR cisternography (NCE-MRC) and contrast
      enhanced MR cisternography (CE-MRC) scans. To the best of our knowledge, this is
      the first case in the literature. In conclusion, in patients with transverse
      fractures of temporal bone, in presence of otic capsule involvement at CT images,
      the inner ear structures and surrounding organs should be carefully evaluated via
      NCE-MRC. In case of a suspicion of a fistula, CE-MRC can help in early diagnosis
      and can also help to visualize the leakage location, which is of paramount
      importance for correct treatment and management of such cases.

PMID- 22639336
TI  - Acromioclavicular joint injuries and reconstructions: a review of expected
      imaging findings and potential complications.
AB  - Shoulder injuries, including acromioclavicular (AC) joint separations, remain a
      common reason for presentation to the emergency room. Although the diagnosis can
      be made apparent through proper history and physical examination by the emergency
      medicine physician, ascertaining the degree of injury can be difficult on the
      basis of clinical evaluation alone. While there is consensus in the literature
      that low-grade AC joint injuries can be treated with conservative management,
      high-grade injuries will generally require surgical intervention. Furthermore,
      the treatment of grade 3 injuries remains controversial, making it incumbent upon
      the radiologist to become comfortable with distinguishing this diagnosis from
      lower or higher grade injuries. Imaging of AC joint injuries after clinical
      evaluation is generally initiated in the emergency room setting with plain film
      radiography; however, on occasion, an alternative modality may be presented to
      the emergency room radiologist for interpretation. As such, it remains important
      to be familiar with the appearance of AC joint separations on a variety of
      modalities. Another possible patient presentation in both the emergent and
      nonemergent setting includes new onset of pain or instability in the postsurgical
      shoulder. In this scenario, the onus is often placed on the radiologist to
      determine whether the pain or instability represents the sequelae of reinjury
      versus a complication of surgery. The purpose of this review is to present an
      anatomically based discussion of imaging findings associated with AC joint
      separations as seen on multiple modalities, as well as to describe and elucidate
      a variety of potential complications which may present to the emergency room
      radiologist.

PMID- 22639339
TI  - Adipocytokines mark insulin sensitivity in euthyroid Hashimoto's patients.
AB  - The relationship between inflammation, Hashimoto's thyroiditis (HT) and insulin
      resistance is still controversial. In this regard, a pretty complete evaluation
      of adipocytokines levels in patients with HT has not been performed so far. We
      assessed retinol binding protein-4 (RBP4), adipocyte-fatty acid binding protein
      (A-FABP), neutrophil gelatinase-associated lipocalin (NGAL) and tumor necrosis
      factor-alpha (TNFalpha) levels in 93 euthyroid HT patients and 51 healthy
      controls (CTL), also evaluating the possible correlation between adipocytokines
      levels and markers of insulin resistance. No significant differences between HT
      patients and CTL in fasting plasma glucose and insulin levels, and HOMA index
      were observed. HT patients had significantly higher RBP4, NGAL and A-FABP levels
      than CTL, while TNFalpha levels did not differ between the two groups. In HT
      patients, RBP4 was significantly related with fT3 and fT4 levels, while A-FABP
      with fT4 only. Moreover, in HT patients, either RBP4 or A-FABP was directly
      associated with plasma insulin and HOMA index. Circulating levels of these
      adipocytokines were not influenced by the presence of antithyroid peroxidase or
      antithyroglobulin autoantibodies or only one of them, neither by autoantibodies
      titer. In conclusion, euthyroid HT patients are characterized by a peculiar
      inflammatory response of the adipose tissue, apparently related to an early
      reduction in insulin sensitivity and to serum thyroid hormone levels, although
      within the normal range. These results suggest that HT patients with high RBP4
      and A-FABP levels might deserve a particular attention, being potentially more
      exposed to develop insulin resistance and increased cardiovascular risk.

PMID- 22639338
TI  - Modeling quasispecies and drug resistance in hepatitis C patients treated with a
      protease inhibitor.
AB  - Telaprevir, a novel hepatitis C virus (HCV) NS3-4A serine protease inhibitor, has
      demonstrated substantial antiviral activity in patients infected with HCV.
      However, drug-resistant HCV variants were detected in vivo at relatively high
      frequency a few days after drug administration. Here we use a two-strain
      mathematical model to explain the rapid emergence of drug resistance in HCV
      patients treated with telaprevir monotherapy. We examine the effects of backward
      mutation and liver cell proliferation on the preexistence of the mutant virus and
      the competition between wild-type and drug-resistant virus during therapy. We
      also extend the two-strain model to a general model with multiple viral strains.
      Mutations during therapy only have a minor effect on the dynamics of various
      viral strains, although they are capable of generating low levels of HCV variants
      that would otherwise be completely suppressed because of fitness disadvantages.
      Liver cell proliferation may not affect the pretreatment frequency of mutant
      variants, but is able to influence the quasispecies dynamics during therapy. It
      is the relative fitness of each mutant strain compared with wild-type that
      determines which strain(s) will dominate the virus population. This study
      provides a theoretical framework for exploring the prevalence of preexisting
      mutant variants and the evolution of drug resistance during treatment with other
      HCV protease inhibitors or polymerase inhibitors.

PMID- 22639340
TI  - Preparation of THP-ester-derived pyridinium-type salts and their reactions with
      various nucleophiles.
AB  - Nucleophilic substitution at the anomeric positions of tetrahydropyranyl (THP)
      and related carbohydrate-derived esters that proceeded through pyridinium-type
      salt intermediates have been developed. Treatment of the 6-substituted alpha
      acetoxy-tetrahydropyrans with TMSOTf (TMS=trimethylsilyl) and 2-substitutited
      pyridines, such as 2-p-tolylpyridine and 2-methoxypyridine, led to the efficient
      generation of cis-pyridinium-type salts. These salts reacted with various
      nucleophiles, such as alcohols, azides, and organozinc reagents, to form
      nucleophilic-substitution products. A characteristic feature of these processes
      was that they took place under mild conditions, which did not affect acid-labile
      protecting groups. Furthermore, the reactions that employed azides and C
      nucleophiles generated 2,6-trans products with high degrees of stereoselectivity.

PMID- 22639341
TI  - Diabetic cardiovascular disease: getting to the heart of the matter.
AB  - Diabetes is a major risk factor for heart disease, and heart disease is
      responsible for substantial morbidity and mortality among people living with
      diabetes. The diabetic metabolic milieu predisposes to aggressive obstructive
      coronary artery disease that causes heart attacks, heart failure, and death.
      Furthermore, diabetes can be associated with heart failure, independent of
      underlying coronary artery disease, hypertension, or valve abnormalities. The
      pathogenesis of the vascular and myocardial complications of diabetes is, as yet,
      incompletely understood. Although a number of medical and surgical approaches can
      improve outcomes in diabetic patients with cardiovascular disease, much remains
      to be learned in order to optimize approaches to these critical complications.

PMID- 22639342
TI  - In vitro uses of human pluripotent stem cell-derived cardiomyocytes.
AB  - Functional cardiomyocytes can be efficiently derived from human pluripotent stem
      cells (hPSCs), which collectively include embryonic and induced pluripotent stem
      cells. This cellular platform presents exciting new opportunities for development
      of pharmacologically relevant in vitro screens to detect cardiotoxicity, validate
      novel drug candidates in preclinical trials and understand complex congenital
      cardiovascular disorders, to advance current clinical therapies. Here, we discuss
      the progress and impediments the field has faced in using hPSC-derived
      cardiomyocytes for these in vitro applications, and highlight that rigorous
      protocol optimisation and standardisation, scalability and automation are
      remaining obstacles for the generation of pure, mature and clinically relevant
      hPSC cardiomyocytes.

PMID- 22639343
TI  - Chromatin modifications associated with diabetes.
AB  - Accelerated rates of vascular complications are associated with diabetes
      mellitus. Environmental factors including hyperglycaemia contribute to the
      progression of diabetic complications. Epidemiological and experimental animal
      studies identified poor glycaemic control as a major contributor to the
      development of complications. These studies suggest that early exposure to
      hyperglycaemia can instigate the development of complications that present later
      in the progression of the disease, despite improved glycaemic control. Recent
      experiments reveal a striking commonality associated with gene-activating
      hyperglycaemic events and chromatin modification. The best characterised to date
      are associated with the chemical changes of amino-terminal tails of histone H3.
      Enzymes that write specified histone tail modifications are not well understood
      in models of hyperglycaemia and metabolic memory as well as human diabetes. The
      best-characterised enzyme is the lysine specific Set7 methyltransferase. The
      contribution of Set7 to the aetiology of diabetic complications may extend to
      other transcriptional events through methylation of non-histone substrates.

PMID- 22639345
TI  - Germ granules and the control of mRNA translation.
AB  - Germ granules are an evolutionarily conserved feature of germ cell cytoplasm and
      are critical for gametogenesis and embryonic development. Germ granules are
      highly enriched for RNA and RNA-binding proteins and are key centers for post
      transcriptional gene regulation in germ cells. Over the last 20 years, the
      molecular events in germ granule function and formation in several organisms have
      begun to be revealed. This review seeks to give an overview of some conserved
      features of germ granules and highlights a conserved strategy for regulating
      translation of maternal mRNAs.

PMID- 22639344
TI  - Enhanced endothelialization of a new stent polymer through surface enhancement
      and incorporation of growth factor-delivering microparticles.
AB  - In this study, we sought to develop strategies for improved endothelialization of
      a new polymer coating for vascular stents. Surface enhancement of the new poly
      1,8-octanediol-co-citric acid (POC) polymer was achieved through conjugation of
      anti-CD34 antibody and incorporation of vascular endothelial growth factor and
      basic fibroblast growth factor-containing poly-lactic-co-glycolic acid
      microparticles to improve capture and proliferation of endothelial progenitor
      cells (EPC) and compared to untreated POC and poly-L-lactic acid (PLLA) polymer.
      Our results indicate that compared to PLLA, POC coating was more hemocompatible,
      with less platelet activation (p = 0.01), thrombogenicity (p < 0.05 for 20 and 30
      min clot formation), and inflammatory response (IL-1beta release, p = 0.0009; TNF
      alpha release, p = 0.004). EPC adhesion and proliferation on POC were
      significantly improved with surface enhancement and microparticle incorporation
      compared to untreated POC (p = 0.006) and PLLA (p = 0.003). These results suggest
      a new strategy for enhancing endothelialization of polymeric coatings of vascular
      prostheses.

PMID- 22639346
TI  - Physiological analysis of silver nanoparticles and AgNO3 toxicity to Spirodela
      polyrhiza.
AB  - Silver nanoparticles (AgNPs) are commonly used in consumer products for their
      antibacterial activity. Silver nanoparticles may adversely influence organisms
      when released into the environment. The present study investigated the effect of
      AgNPs on the growth, morphology, and physiology of the aquatic plant duckweed
      (Spirodela polyrhiza). The toxicity of AgNPs and AgNO(3) was also compared. The
      results showed that silver content in plant tissue increased significantly with
      higher concentrations of AgNPs and AgNO(3) . Silver nanoparticles and AgNO(3)
      significantly decreased plant biomass, caused colonies of S. polyrhiza to
      disintegrate, and also resulted in root abscission. Physiological analysis showed
      that AgNPs and AgNO(3) significantly decreased plant tissue nitrate-nitrogen
      content, chlorophyll a (Chl a) content, chlorophyll a/b (Chl a/b), and
      chlorophyll fluorescence (Fv/Fm). Changes in soluble carbohydrate and proline
      content were also detected after both AgNO(3) and AgNPs treatment. However, after
      192 h of recovery, total chlorophyll content increased, and Fv/Fm returned to
      control level. Median effective concentration (EC50) values for Chl a and
      phosphate content showed that AgNO(3) was more toxic than AgNPs (EC50 values:
      16.10 +/- 0.75 vs 7.96 +/- 0.81 and 17.33 +/- 4.47 vs 9.14 +/- 2.89 mg Ag L(-1) ,
      respectively), whereas dry-weight EC50 values showed that AgNPs were more toxic
      than AgNO(3) (13.39 +/- 1.06 vs 17.67 +/- 1.16 mg Ag L(-1) ).

PMID- 22639347
TI  - Examination of forensic entomology evidence using computed tomography scanning:
      case studies and refinement of techniques for estimating maggot mass volumes in
      bodies.
AB  - A new technique has recently been developed for estimating the volume of maggot
      masses on deceased persons using post-mortem CT scans. This allows volume to be
      measured non-invasively and factored into maggot mass temperature calculations
      for both casework and research. Examination of admission scans also allows
      exploration of entomological evidence in anatomical areas not usually exposed by
      autopsy (e.g. nasal cavities and facial sinuses), and before autopsy disrupts the
      maggot distribution on a body. This paper expands on work already completed by
      providing the x-ray attenuation coefficient by way of Hounsfield unit (HU) values
      for various maggot species, maggot masses and human tissue adjacent to masses.
      Specifically, this study looked at the HU values for four forensically important
      blowfly larvae: Lucilia cuprina, L. sericata, Calliphora stygia and C. vicina.
      The Calliphora species had significantly lower HU values than the Lucilia
      species. This might be explained by histological analysis, which revealed a non
      significant trend, suggesting that Calliphora maggots have a higher fat content
      than the Lucilia maggots. It is apparent that the variation in the x-ray
      attenuation coefficient usually precludes its use as a tool for delineating the
      maggot mass from human tissue and that morphology is the dominant method for
      delineating a mass. This paper also includes three case studies, which reveal
      different applications for interpreting entomological evidence using post-mortem
      CT scans.

PMID- 22639348
TI  - Interpreting the formation of bloodstains on selected apparel fabrics.
AB  - Bloodstain pattern analysis (BPA) is the investigation and interpretation of
      blood deposited at crime scenes. However, the interaction of blood and apparel
      fabrics has not been widely studied. In this work, the development of bloodstains
      (passive, absorbed and transferred) dropped from three different heights (500,
      1,000, 1,500 mm) on two cotton apparel fabrics (1 * 1 rib knit, drill) was
      investigated. High-speed video was used to investigate the interaction of the
      blood and fabric at impact. The effect of drop height on the development of
      passive, absorbed and transferred bloodstains was investigated using image
      analysis and statistical tools. Visually, the passive bloodstain patterns
      produced on the technical face of fabrics from the different drop heights were
      similar. The blood soaked unequally through to the technical rear of both
      fabrics. Very little blood was transferred between a bloody fabric and a second
      piece of fabric. Statistically, drop height did not affect the size of the parent
      bloodstain (wet or dry), but did affect the number of satellite bloodstains
      formed. Some differences between the two fabrics were noted, therefore fabric
      structure and properties must be considered when conducting BPA on apparel
      fabrics.

PMID- 22639349
TI  - ST waveform analysis versus cardiotocography alone for intrapartum fetal
      monitoring: a meta-analysis of randomized trials.
AB  - OBJECTIVE: To estimate the effectiveness of intrapartum ST waveform analysis
      (STAN) versus cardiotocography (CTG) alone in prevention of metabolic acidosis.
      STUDY DESIGN: Meta-analysis of randomized trials comparing intrapartum fetal
      monitoring utilizing STAN with CTG versus CTG alone. Primary outcome was neonatal
      metabolic acidosis, defined as umbilical arterial pH <7.05 and base deficit >12
      mmol/L. RESULTS: Five randomized trials including 15,303 singletons, vertex,
      term, or near-term pregnancies met inclusion criteria and were analyzed. Compared
      with CTG alone, STAN with CTG was associated with similar incidences of metabolic
      acidosis (0.81% versus 1.12%, relative risk [RR] 0.80; 95% confidence interval
      [CI] 0.44 to 1.47), perinatal death, neonatal encephalopathy, Apgar score <7 at 5
      minutes, admission to neonatal intensive care unit, and cesarean delivery.
      Operative vaginal delivery (OVD) was lower in the STAN with CTG compared with CTG
      alone (13.56% versus 15.20%; RR 0.89; 95% CI 0.83 to 0.97). CONCLUSION: There is
      no difference in perinatal outcomes between STAN with CTG compared with CTG
      alone, except for lower rate of OVD.

PMID- 22639350
TI  - Optimum click rate for neurodevelopmental evaluation using auditory brainstem
      response in premature infants.
AB  - OBJECTIVE: To determine the optimal click rate (CR) for neurodevelopmental
      assessment using auditory brainstem evoked response (ABR) in preterm infants.
      STUDY DESIGN: A prospective study was performed in 17 preterm infants at 34
      weeks' postmenstrual age. Three separate ABRs were performed a few minutes apart
      on each subject using three different click rates (CRs): 19.9/s, 29.9/s, and
      69.9/s. An ABR response with waves I, III, and V identifiable and measurable was
      defined as a pass response. The CR associated with the highest frequency of pass
      responses was considered optimal, or if two CRs were tied for the highest
      frequency, then the faster of the two CR was deemed best. RESULTS: The frequency
      of pass responses for 29.9/s and 19.9/s CR was 100% and was significantly higher
      compared with 82% frequency with 69.9/s CR. There was no difference in latencies,
      interpeak latencies, and amplitudes of waves between 19.9/s and 29.9/s CR;
      however, standard deviations of interpeak latencies were larger with 19.9/s
      compared with 29.9/s CR. CONCLUSION: Our data suggest that 29.9/s is the optimal
      CR for neurodevelopmental assessment using ABR. Because of smallest variance in
      interpeak latencies, the sample size requirement will be lowest using 29.9/s CR
      with secondary reduction in cost and time.

PMID- 22639351
TI  - Maternal-fetal medicine subspecialists' provision of second-trimester termination
      services.
AB  - OBJECTIVE: Most abortions for pregnancy complications occur in the second
      trimester. Little is known about whether maternal-fetal medicine subspecialists
      (MFMs) perform terminations for these women. STUDY DESIGN: We surveyed all
      members of Society of Maternal Fetal Medicine by e-mail or mail regarding second
      trimester abortion provision. We conducted analyses of whether MFMs perform
      abortions, by what method, and how frequently. RESULTS: Our response rate was
      32.4% (689/2,125). Over two-thirds of respondents perform either dilation and
      evacuation (D&E) or induction; 31% perform D&Es. Male gender, frequent chorionic
      villus sampling provision, and being trained in D&E during fellowship are
      associated with performing D&Es. Nonprovision of any second-trimester abortion is
      significantly associated with age over 50, nonacademic practice setting, and less
      supportive abortion attitudes (p < 0.001). A nonsignificant trend toward
      association between south/southeast region and nonprovision of any second
      trimester abortion is seen (p = 0.09). CONCLUSION: Many MFMs include D&E and
      induction termination services in their practice. Supporting current D&E
      providers and expanding training options for MFMs may optimize care for women
      diagnosed with serious pregnancy complications.

PMID- 22639352
TI  - Prediction of neonatal metabolic acidosis in women with a singleton term
      pregnancy in cephalic presentation: an external validation study.
AB  - OBJECTIVE: To externally validate two previously developed prognostic models that
      predict the risk for developing metabolic acidosis in newborns using both
      antepartum (model 1) and intrapartum (combined with antepartum, model 2) risk
      factors: parity, previous cesarean section, maternal diabetes mellitus,
      gestational age, induced onset of labor, meconium-stained amniotic fluid, and use
      of ST analysis. STUDY DESIGN: The two prediction models were applied in women in
      active labor at more than 36 gestational weeks with singleton fetuses in cephalic
      presentation and with high-risk pregnancies (n = 5049) who were included in a
      Swedish randomized trial between December 1, 1998, and June 4, 2000. The
      prognostic ability of the models was determined using calibration and
      discrimination measures. RESULTS: Of 5049 infants in the validation population,
      54 (1.1%) suffered from metabolic acidosis. After adjustment for incidence
      differences between the Dutch and Swedish cohorts, the prognostic models showed
      good calibration and moderate overall discrimination (C statistic 0.63, 95%
      confidence interval [CI] 0.55 to 0.71; and 0.64, 95% CI 0.55 to 0.72), for models
      1 and 2, respectively). CONCLUSION: External validation of the clinical
      prediction models for metabolic acidosis in Swedish infants showed good
      calibration and moderate discriminative ability. Updating of the models to
      enhance their predictive abilities seems indicated.

PMID- 22639353
TI  - Are obstetrician-gynecologists satisfied with their maternal-fetal medicine
      consultants? A survey.
AB  - OBJECTIVE: To survey generalist obstetrician-gynecologists about their
      satisfaction with and patterns of referral to maternal-fetal medicine (MFM)
      specialists. STUDY DESIGN: A survey was sent three times to 1030 randomly
      selected American Congress of Obstetricians and Gynecologists members across the
      country, and results were tabulated. RESULTS: A total of 516 surveys (50%) were
      returned; 68% of respondents were satisfied (S) with available MFM services and
      31% were not satisfied (Not S). S and Not S respondents were similar with respect
      to age, gender, years in practice, type of practice, hours worked per week,
      proximity to MFM specialists, number of deliveries per year, and level of nursery
      in their hospital. Reasons for dissatisfaction included: MFM specialist not
      readily available (49%), during the day (26%), at night (35%), or on weekends
      (36%); MFM specialist unwilling to take care of hospitalized patients (26%); or
      MFM specialist does only ultrasound, chorionic villus sampling, and amniocentesis
      (32%). Although some generalists do not consult MFM specialists frequently, the
      majority of both S and Not S respondents would request an MFM consult or
      comanagement for 26 of 38 specific maternal, fetal, and obstetric
      diagnoses/complications. CONCLUSION: The majority of obstetrician-gynecologists
      are satisfied with their MFM support. The dissatisfaction expressed by 31% of
      generalists might be ameliorated if individual MFM specialists increased their
      availability and/or broadened their scope of practice.

PMID- 22639354
TI  - Perceptions of a strategy to prevent and relieve care provider distress in the
      neonatal intensive care unit.
AB  - BACKGROUND: A Midwestern neonatal intensive care unit (NICU) employs a
      multidisciplinary conference, the Comprehensive Care Round (CCR), to facilitate
      communication and consensus building and thereby prevent or address moral
      distress within the health care team. METHODS: A cross-sectional survey, 3 years
      after implementation of CCR, to evaluate health care providers' (HCP) perceptions
      of comfort with expressing distress, support from team members in care situations
      that evoke moral distress, barriers to communication, and attainment of CCR
      objectives. RESULTS: Of 370 HCP, 116 (31%) participated in the survey (42%
      nurses, 37% allied health, and 21% medical); 51% had previously attended CCR. CCR
      attendance was higher among HCP aged >35 years, those who cared for CCR patients,
      and nonnurses. Neonatologist were more likely than others (44% versus 4%, p
      <0.01) to report that referred cases were not overdue for discussion and that
      families appreciated the attention their child received from CCR. Of note, HCP
      who were comfortable with expressing distress also felt supported by team members
      (R = 0.5, p <0.001). CONCLUSION: CCR, developed to prevent or address moral
      distress, occurs later than most NICU HCP consider appropriate and appears to
      better serve HCP who are already comfortable with discussing moral distress.
      Helping HCP become comfortable with crucial conversations should support
      meaningful participation and contribution to multidisciplinary conferences.

PMID- 22639355
TI  - The effects of prostaglandin E1 and prostaglandin E2 on in vitro myometrial
      contractility and uterine structure.
AB  - OBJECTIVE: To estimate the effects of prostaglandin E1 (PGE1) and E2 (PGE2) on
      myometrial contractility and structure in vitro. STUDY DESIGN: Myometrial strips
      from 18 women were incubated with PGE1 (10-5 mol/L), PGE2 (10-5 mol/L), or
      solvent (CTR) for up to 360 minutes in organ chambers for isometric tension
      recording. The area under the contraction curve, total collagen content, and
      percentage of the area covered by connective tissue were calculated at various
      time periods. RESULTS: PGE1 significantly increased in vitro myometrial
      contractility up to 90 minutes when compared with PGE2 and CTR (p < 0.01) and up
      to 180 minutes as compared with PGE2 (p < 0.05). After 360 minutes, CTR and PGE1
      samples had lower total collagen content and area covered by connective tissue
      than PGE2 (p < 0.01). CONCLUSION: The effects of prostaglandins on the uterus
      cannot be solely explained by contractility. Treatment with PGE1 significantly
      increased myometrial contractions and decreased both total collagen content and
      the area covered by connective tissue. Such findings may explain the higher rates
      of vaginal delivery, tachysystole, and uterine rupture associated with PGE1 use.

PMID- 22639356
TI  - Use of partition coefficients in flow-limited physiologically-based
      pharmacokinetic modeling.
AB  - Permeability-limited two-subcompartment and flow-limited, well-stirred tank
      tissue compartment models are routinely used in physiologically-based
      pharmacokinetic modeling. Here, the permeability-limited two-subcompartment model
      is used to derive a general flow-limited case of a two-subcompartment model with
      the well-stirred tank being a specific case where tissue fractional blood volume
      approaches zero. The general flow-limited two-subcompartment model provides a
      clear distinction between two partition coefficients typically used in PBPK: a
      biophysical partition coefficient and a well-stirred partition coefficient. Case
      studies using diazepam and cotinine demonstrate that, when the well-stirred tank
      is used with a priori predicted biophysical partition coefficients, simulations
      overestimate or underestimate total organ drug concentration relative to flow
      limited two-subcompartment model behavior in tissues with higher fractional blood
      volumes. However, whole-body simulations show predicted drug concentrations in
      plasma and lower fractional blood volume tissues are relatively unaffected. These
      findings point to the importance of accurately determining tissue fractional
      blood volume for flow-limited PBPK modeling. Simulations using biophysical and
      well-stirred partition coefficients optimized with flow-limited two
      subcompartment and well-stirred models, respectively, lead to nearly identical
      fits to tissue drug distribution data. Therefore, results of whole-body PBPK
      modeling with diazepam and cotinine indicate both flow-limited models are
      appropriate PBPK tissue models as long as the correct partition coefficient is
      used: the biophysical partition coefficient is for use with two-subcompartment
      models and the well-stirred partition coefficient is for use with the well
      stirred tank model.

PMID- 22639357
TI  - Improved bioethanol production using fusants of Saccharomyces cerevisiae and
      xylose-fermenting yeasts.
AB  - The present research deals with the development of a hybrid yeast strain with the
      aim of converting pentose and hexose sugar components of lignocellulosic
      substrate to bioethanol by fermentation. Different fusant strains were obtained
      by fusing protoplasts of Saccharomyces cerevisiae and xylose-fermenting yeasts
      such as Pachysolen tannophilus, Candida shehatae and Pichia stipitis. The fusants
      were sorted by fluorescent-activated cell sorter and further confirmed by
      molecular characterization. The fusants were evaluated by fermentation of glucose
      xylose mixture and the highest ethanol producing fusant was used for further
      study to ferment hydrolysates produced by acid pretreatment and enzymatic
      hydrolysis of cotton gin waste. Among the various fusant and parental strains
      used under present study, RPR39 was found to be stable and most efficient strain
      giving maximum ethanol concentration (76.8 +/- 0.31 g L(-1)), ethanol
      productivity (1.06 g L(-1) h(-1)) and ethanol yield (0.458 g g(-1)) by
      fermentation of glucose-xylose mixture under test conditions. The fusant has also
      shown encouraging result in fermenting hydrolysates of cotton gin waste with
      ethanol concentration of 7.08 +/- 0.142 g L(-1), ethanol yield of 0.44 g g(-1),
      productivity of 0.45 g L(-1) h(-1) and biomass yield of 0.40 g g(-1).

PMID- 22639358
TI  - Mushroom polysaccharides and lipids synthesized in liquid agitated and static
      cultures. Part II: study of Volvariella volvacea.
AB  - Volvariella volvacea strains were studied in relation with their ability to
      produce biomass, lipids and polysaccharides. Firstly, screening of four strains
      (AMLR 188, 190, 191 and 192) was performed in agar cultures, where the mycelial
      growth rate of the strains was measured, and in static liquid cultures, where the
      production of biomass, the biosynthesis of total cellular lipids and the
      consumption of glucose were monitored. For all strains, biomass production was
      significant (13-15 g l(-1)) and total lipid in dry weight (%, w/w) ranged from 3
      to 12 %. Afterwards, a detailed kinetic analysis of mycelial biomass, extra- and
      intra- cellular polysaccharides (EPS, IPS, respectively) as well as lipid
      production by a V. volvacea selected strain was conducted in submerged static and
      agitated cultures. Maximum values of 15 g l(-1) biomass, ~1.0 g l(-1) EPS and 5.5
      g l(-1) IPS were recorded. Agitation did not have severe impact on biomass, EPS
      and IPS production, but it increased total lipid in dry weight quantities. EPS,
      IPS and lipid in dry weight values decreased with time. Glucose was the major
      cellular carbohydrate detected. Total fatty acid analysis of cellular lipids was
      performed for all V. volvacea strains and linoleic acid (Delta9,12)C18:2 was
      predominant. Neutral lipids constituted the major fraction of cellular lipids,
      but their quantity decreased as fermentation proceeded. Phospholipids were the
      most saturated lipid fraction.

PMID- 22639359
TI  - Effect of microaerobic fermentation in preprocessing fibrous lignocellulosic
      materials.
AB  - Amending soil with organic matter is common in agricultural and logging
      practices. Such amendments have benefits to soil fertility and crop yields. These
      benefits may be increased if material is preprocessed before introduction into
      soil. We analyzed the efficiency of microaerobic fermentation (MF), also referred
      to as Bokashi, in preprocessing fibrous lignocellulosic (FLC) organic materials
      using varying produce amendments and leachate treatments. Adding produce
      amendments increased leachate production and fermentation rates and decreased the
      biological oxygen demand of the leachate. Continuously draining leachate without
      returning it to the fermentors led to acidification and decreased concentrations
      of polysaccharides (PS) in leachates. PS fragmentation and the production of
      soluble metabolites and gases stabilized in fermentors in about 2-4 weeks. About
      2 % of the carbon content was lost as CO(2). PS degradation rates, upon
      introduction of processed materials into soil, were similar to unfermented FLC.
      Our results indicate that MF is insufficient for adequate preprocessing of FLC
      material.

PMID- 22639360
TI  - Expression of codon-optmized phosphoenolpyruvate carboxylase gene from Glaciecola
      sp. HTCC2999 in Escherichia coli and its application for C4 chemical production.
AB  - We examined the expression of the phosphoenolpyruvate carboxylase (PEPC) gene
      from marine bacteria in Escherichia coli using codon optimization. The codon
      optimized PEPC gene was expressed in the E. coli K-12 strain W3110. SDS-PAGE
      analysis revealed that the codon-optimized PEPC gene was only expressed in E.
      coli, and measurement of enzyme activity indicated the highest PEPC activity in
      the E. coli SGJS112 strain that contained the codon-optimized PEPC gene. In
      fermentation assays, the E. coli SGJS112 produced the highest yield of
      oxaloacetate using glucose as the source and produced a 20-times increase in the
      yield of malate compared to the control. We concluded that the codon optimization
      enabled E. coli to express the PEPC gene derived from the Glaciecola sp.
      HTCC2999. Also, the expressed protein exhibited an enzymatic activity similar to
      that of E. coli PEPC and increased the yield of oxaloacetate and malate in an E.
      coli system.

PMID- 22639361
TI  - Production, purification, immobilization, and characterization of a thermostable
      beta-galactosidase from Aspergillus alliaceus.
AB  - A fungal strain isolated from rotten banana and identified as Aspergillus
      alliaceus was found capable of producing thermostable extracellular beta
      galactosidase enzyme. Optimum cultural conditions for beta-galactosidase
      production by A. alliaceus were as follows: pH 4.5; temperature, 30  degrees C;
      inoculum age, 25 h; and fermentation time, 144 h. Optimum temperature, time, and
      pH for enzyme substrate reaction were found to be 45  degrees C, 20 min, and 7.2,
      respectively, for crude and partially purified enzyme. For immobilized enzyme
      substrate reaction, these three variable, temperature, time, and pH were
      optimized at 50  degrees C, 40 min, and 7.2, respectively. Glucose was found to
      inhibit the enzyme activity. The K(m) values of partially purified and
      immobilized enzymes were 170 and 210 mM, respectively. Immobilized enzyme
      retained 43 % of the beta-galactosidase activity of partially purified enzyme.
      There was no significant loss of activity on storage of immobilized beads at 4 
      degrees C for 28 days. Immobilized enzyme retained 90 % of the initial activity
      after being used four times.

PMID- 22639362
TI  - Bioligninolysis: recent updates for biotechnological solution.
AB  - Bioligninolysis involves living organisms and/or their products in degradation of
      lignin, which is highly resistant, plant-originated polymer having three
      dimensional network of dimethoxylated (syringyl), monomethoxylated (guaiacyl),
      and non-methoxylated (p-hydroxyphenyl) phenylpropanoid and acetylated units. As a
      major repository of aromatic chemical structures on earth, lignin bears paramount
      significance for its removal owing to potential application of bioligninolytic
      systems in industrial production. Early reports illustrating the discovery and
      cloning of ligninolytic biocatalysts in fungi was truly a landmark in the field
      of enzymatic delignification. However, the enzymology for bacterial
      delignification is hitherto poorly understood. Moreover, the lignin-degrading
      bacterial genes are still unknown and need further exploration. This review deals
      with the current knowledge about ligninolytic enzyme families produced by fungi
      and bacteria, their mechanisms of action, and genetic regulation and
      reservations, which render them attractive candidates in biotechnological
      applications.

PMID- 22639363
TI  - Characterization and activity determination of the human protein phosphatase 2A
      catalytic subunit alpha expressed in insect larvae.
AB  - Protein phosphatase 2A is the major enzyme that dephosphorylates the
      serine/threonine residues of proteins in the cytoplasm of animal cells. This
      phosphatase is most strongly inhibited by okadaic acid. Besides okadaic acid,
      several other toxins and antibiotics have been shown to inhibit protein
      phosphatase 2A, including microsystin-LR, calyculin-A, tautomycib, nodularin,
      cantharidine, and fostriecin. This makes protein phosphatase 2A a valuable tool
      for detecting and assaying these toxins. High-scale production of active protein
      phosphatase 2A requires processing kilograms of animal tissue and involves
      several chromatographic steps. To avoid this, in this work we report the
      recombinant expression and characterization of the active catalytic subunit alpha
      of the protein phosphatase 2A in Trichoplusia ni insect larvae. Larvae were
      infected with baculovirus carrying the coding sequence for the catalytic subunit
      alpha of protein phosphatase 2A under the control of the polyhedrin promoter and
      containing a poly-His tag in the carboxyl end. The catalytic subunit was
      identified in the infected larvae extracts, and it was calculated to be present
      at 250 MUg per gram of infected larvae, by western blot. Affinity chromatography
      was used for protein purification. Protein purity was determined by western blot.
      The activity of the enzyme, determined by the p-nitrophenyl phosphate method, was
      94 MUmol/min/mg of purified protein. The catalytic subunit was further
      characterized by inhibition with okadaic acid and dinophysis toxin 2. The results
      presented in this work show that this method allows the production of large
      quantities of the active enzyme cost-effectively. Also, the enzyme activity was
      stable up to 2 months at -20  degrees C.

PMID- 22639364
TI  - The use of PAMAM dendrimers as a platform for laccase immobilization: kinetic
      characterization of the enzyme.
AB  - The kinetic behavior of the enzyme laccase in solution and immobilized onto
      carbon platforms using poly(amido amine) (PAMAM) dendrimers has been
      investigated. The results with the immobilized enzymes have demonstrated that
      almost ten times more enzyme on the carbon support is required for satisfactory
      kinetic rates to be achieved. Furthermore, the study as a function of the
      substrate concentration revealed that the kinetic behavior of the enzyme in
      solution fits the Michaelis-Menten model. However, when the enzyme is immobilized
      onto the carbon surface, the catalyzed reaction follows a particular kinetic
      behavior with apparent positive cooperativity. The highest activity with laccase
      (in solution or immobilized) is achieved around pH 4.5, and the substrate
      conversion rate clearly diminishes with rising pH. The optimum temperature lies
      around 60  degrees C. The enzyme displays good catalytic activity in a wide range
      of pH and temperature values. The stability tests evidenced that there is no
      appreciable reduction in the enzymatic activity after immobilization within the
      first 30 days. Taking into account both the kinetic and stability tests, one can
      infer that the use of PAMAM dendrimers seems to be a very attractive approach for
      the immobilization of enzymes, as well as a feasible and useful methodology for
      the anchoring of enzymes with potential application in many biotechnological
      areas.

PMID- 22639365
TI  - Fractionation of sugarcane bagasse using a combined process of dilute acid and
      ionic liquid treatments.
AB  - Biorefineries processing lignocellulose will produce chemicals and fuels from
      chemical constituents, cellulose, hemicelluloses, and lignin to replace fossil
      derived products. Fractionation of sugarcane bagasse into three pure streams of
      chemical constituents was addressed through dissolution of constituents with the
      ionic liquids, 1-ethyl-3-methylimidazolium acetate ([EMiM]CH(3)COO) or 1-butyl-3
      methylimidazolium methyl sulfate ([BMiM]MeSO(4)). Constituents were isolated from
      the reaction mixture with the anti-solvents acetone (A), acetone-water (AW), and
      sodium hydroxide (NaOH). Delignification was enhanced by NaOH, although resulting
      in impure product streams. Xylose pre-extraction (75 % w/w) by dilute acid
      pretreatment, prior to ionic liquid treatment, improved lignin purity after anti
      solvent separation. Fractionation efficiency of the combined process was
      maximized (84 %) by ionic liquid treatment at 125  degrees C for 120 min,
      resulting in 80.2 % (w/w) lignin removal and 76.5 % (w/w) lignin recovery. Ionic
      liquids achieved similar degrees of delignification, although fully digestible
      cellulose-rich solids were produced only by [EMiM]CH(3)COO treatment.

PMID- 22639366
TI  - Production of galanthamine by Leucojum aestivum shoots grown in different
      bioreactor systems.
AB  - The production of galanthamine by shoots of Leucojum aestivum grown in different
      bioreactor systems (shaking and nonshaking batch culture, temporary immersion
      system, bubble bioreactor, continuous and discontinuous gassing bioreactor) under
      different culture conditions was studied. The influence of the nutrient medium,
      weight of inoculum, and size of bioreactor on both growth and galanthamine
      production was studied. The maximal yield of galanthamine (19.416 mg) was
      achieved by cultivating the L. aestivum shoots (10 g of fresh inoculum) in a
      temporary immersion system in a 1-L bioreactor vessel which was used as an
      airlift culture vessel, gassing 12 times per day (5 min).

PMID- 22639367
TI  - Morindone, an anthraquinone, intercalates DNA sans toxicity: a spectroscopic and
      molecular modeling perspective.
AB  - For the first time, interaction between non-toxic anthraquinone morindone with
      both natural and synthetic DNA duplexes has been demonstrated in this paper.
      Detailed analyses of the binding of morindone with DNA via UV-vis, FTIR, and
      circular dichroism spectroscopies were carried out. In addition, bioinformatics
      tools have been employed to scrutinize the binding of the dye with DNA in silico.
      Results represent morindone to be a better binder with a score of -5.79 compared
      to EtBr (known mutagenic intercalator) recorded at -5.02. Further interaction is
      accentuated by the microscope-assisted evidence of nuclear specific staining of
      tissues by morindone. The electrophoretic analysis reveals the efficacy endowed
      within morindone dye in rendering protection to DNA exposed to H(2)O(2) damage
      and thereby conferring it safe to the nucleic acid. As DNA is often the target
      for majority of anticancer and antibiotic drugs, study on the interaction between
      molecules like morindone and DNA has relevance and implications in several
      biological applications including cancer therapy. Thus, we propose that morindone
      can also be harnessed as a diagnostic probe for DNA structure in addition to DNA
      directed therapeutics.

PMID- 22639368
TI  - Strategies for enhancing extracellular secretion of recombinant cyclodextrin
      glucanotransferase in E. coli.
AB  - Cyclodextrin glycosyltransferase (CGTase) is an enzyme that produces
      cyclodextrins from starch by an intramolecular transglycosylation reaction. Due
      to the increasing industrial application of cyclodextrins in many fields such as
      pharmacy, agriculture, biotechnology, food, environment and cosmetics, CGTases
      have attracted the attention of many scientific researches. Undoubtedly, due to
      its well-known genetic properties, simplicity and capacity to accommodate many
      foreign proteins, Escherichia coli remains the most widely used host for
      recombinant proteins production and thus for CGTases. Like all other proteins,
      CGTases are originally produced in the cytoplasm, but expressing them out into
      the periplasm or further to the culture media is preferred due to several
      advantages such as simplified downstream processing and high expression level
      which otherwise would be costly, complicated and time consuming. Since E. coli,
      other than some of its degradative enzymes and toxins, does not normally secrete
      proteins extracellularly, many strategies have been tried to overcome this
      drawback using the recombinant technologies. Unfortunately, oversecretion of the
      recombinant proteins most of the time results in the formation of inactive
      protein aggregates, called inclusion bodies, which result as a consequence of the
      burden caused by the methods meant to enhance the secretion. Thus, in this mini
      review, the few but most commonly used strategies which offered a solution to the
      enhancement of extracellular secretion of CGTase in its native state are
      discussed.

PMID- 22639369
TI  - Diet, residential origin, and pathology at Machu Picchu, Peru.
AB  - Pathological conditions in human skeletal remains provide a wealth of information
      about archaeological populations, but many are limited in their interpretive
      significance by their nonspecific etiologies. This study analyzes three common
      pathological conditions known to manifest in infancy and childhood in the
      skeletal population from Machu Picchu, Peru (N = 74) with published carbon,
      nitrogen, oxygen, strontium, and lead isotopic data (Turner et al.: J Archaeol
      Sci 36 (2009) 317-332; Turner et al.: Chungara: Revista de Antropologia Chilena
      42 (2010) 515-524) to distinguish early-life diet from residential origins as
      significantly associated with pathologies among the site's inhabitants. Analyses
      of variance indicate highly significant variation between enamel delta(18)O
      values, which serve as a rough proxy of local environment, and both cribra
      orbitalia (CO) and porotic hyperostosis (PH), generally understood to be markers
      of anemia. Results tentatively suggest that individuals manifesting these lesions
      may have lived closer to the arid coasts; however, no significant variation was
      found in parameters of diet (enamel delta(13) C(carbonate), dentin delta(13)
      C(collagen), dentin delta(15)N) by either CO or PH, suggesting that the primary
      factors causing anemia may have been more significantly related to residential
      origin rather than diet. Linear enamel hypoplasia (LEH) frequency significantly
      varied by both dietary and residential parameters, supporting models of LEH
      formation from a synergy of dietary and environmental factors. These results
      support previous research on the etiology of PH in the Andes; they also represent
      a useful approach to refining site-specific interpretations of pathological
      conditions in archaeological populations, and exploring etiological variation
      between populations.

PMID- 22639370
TI  - Identification of novel transcription-regulating genes expressed during murine
      molar development.
AB  - BACKGROUND: The mechanism of tooth development is a complex process regulated by
      numerous genes including transcription factors, growth factors, and other intra-
      and extracellular molecules. Especially, transcription factors play a central
      role in gene expression, regulating a wide spectrum of biological processes
      including organogenesis. Substantial evidence has been demonstrated by a number
      of studies using genetically engineered animal models. However, detailed
      molecular mechanisms of tooth development have not been completely elucidated,
      partially because numerous genes that play essential roles in tooth development
      remain unidentified. RESULTS: In this study, we conducted an expression-based
      screening using gene expression database and in situ hybridization assays. Based
      on the gene expression database "EMBRYS," 207 out of 1,520 genes were expressed
      in the maxillary and/or mandibular processes and thus were selected for further
      analysis by section in situ hybridization. Among these candidates, 28 genes were
      newly identified as potential factors associated with tooth development by in
      situ hybridization assays with frontal sections of embryonic day 13.5 and 14.5
      mouse embryos. The expression patterns were also examined at embryonic day 16.5
      and 18.5. CONCLUSIONS: These results will contribute to elucidating the
      mechanisms of tooth development and to improving the technology for regeneration
      of tooth.

PMID- 22639371
TI  - Label-free, non-derivatization CRET detection platform for 6-mercaptopurine based
      on the distance-dependent optical properties of gold nanoparticles.
AB  - A label-free, non-derivatization chemiluminescence resonance energy transfer
      (CRET) detection platform has been developed for the detection of the non
      fluorescent small molecule 6-mercaptopurine. This CRET process arose from a
      chemiluminescent (CL) donor-acceptor system in which the reaction of bis(2,4,6
      trichlorophenyl)oxalate (TCPO)-H(2)O(2)-fluorescein (maximum emission at 521.6
      nm) served as the donor and gold nanoparticles (AuNPs, maximum absorption at
      520.0 nm) served as the acceptor. This process caused a significant decrease in
      the CL signal of the TCPO-H(2)O(2)-fluorescein reaction. The presence of 6
      mercaptopurine induced an aggregation of AuNPs with the assistance of Cu(2+) ions
      through cooperative metal-ligand interactions that was accompanied by a distinct
      change in color and optical properties. The maximum absorption band of the AuNPs
      was red-shifted to 721.0 nm and no longer overlapped with the CL spectrum of the
      reaction; as a result, the CL signal was restored. This CRET system exhibited a
      wide linear range, from 9.0 nmol L(-1) to 18.0 MUmol L(-1), and a low detection
      limit (0.62 nmol L(-1)) for 6-mercaptopurine. The applicability of the proposed
      CRET system was evaluated by analysis of 6-mercaptopurine in spiked human plasma
      samples.

PMID- 22639373
TI  - Reversible base coordination to a disilene.

PMID- 22639374
TI  - The WOMENs trial: how should I interpret the results?

PMID- 22639375
TI  - "How I do it"--radical right colectomy with side-to-side stapled ileo-colonic
      anastomosis.
AB  - BACKGROUND AND OBJECTIVE: Standardization of surgical technique helps to
      reproduce excellent clinical outcomes, especially in teaching institutions. We
      aim to describe in detail our established approach for oncological right
      colectomy. TECHNIQUE: The right colon is mobilized in a five-step latero-inferior
      approach starting off with the terminal ileum, visualizing the duodenum and the
      head of pancreas. The ascending colon is dissected from the retroperitoneum, and
      takedown of the hepatic flexure is completed coming retrograde from the
      transverse colon. Transection of the remaining retroperitoneal attachments
      completes exposure of the duodenum and mobilization of the right colon. Ileocolic
      vessels are dissected out and divided close to their origin, and the mesocolon is
      divided. We then establish intestinal continuity by use of a side-to-side stapled
      technique. The arms of a linear cutting stapler are inserted via transverse
      incisions at the anti-mesenteric sides of the terminal ileum and the transverse
      colon (tenia) and fired. The enterotomy site is closed by removal of the specimen
      using a second transverse firing of the linear cutting stapler. An important
      final step is the reinforcement of the anastomotic ends and the crossing of the
      staple lines; an omental patch and closure of the mesenteric window are optional.
      CONCLUSION: The suggested standardized five-step lateral-to-medial dissection of
      the right colon and the three-step side-to-side stapled technique for ileo
      colonic anastomosis are easy to learn and to reproduce. Careful adherence to
      pivotal technical details will help to obtain an optimal oncological outcome and
      a consistently low leak rate around 2%.

PMID- 22639376
TI  - Anterior 90 degrees  partial vs Nissen fundoplication--5 year follow-up of a
      single-centre randomised trial.
AB  - INTRODUCTION: Nissen fundoplication can be followed by side effects, and this has
      driven modifications, including partial fundoplications. We previously reported
      early outcomes from a randomised trial of Nissen vs anterior 90 degrees  partial
      fundoplication. This paper reports 5-year follow-up outcomes to determine whether
      anterior 90 degrees  fundoplication achieves a satisfactory longer-term outcome.
      METHODS: From February 1999 to August 2003, 79 patients were randomised to Nissen
      vs anterior 90 degrees  fundoplication. Patients were followed yearly using a
      standardized clinical questionnaire which included symptom scores to assess
      heartburn, dysphagia, other post-fundoplication side effects and overall
      satisfaction with the outcome. Five-year clinical outcomes were analysed.
      RESULTS: Seventy-four patients were available for follow-up at 5 years. There
      were no significant differences for heartburn or satisfaction, although more
      patients used antisecretory medication after anterior 90 degrees  fundoplication
      (29.7 vs 8.1 %). Dysphagia was greater after Nissen fundoplication when measured
      by an analogue score for solid food and a composite dysphagia score. Symptoms of
      bloating were more common following Nissen fundoplication (80.0 vs 32.4 %), and
      less patients could eat a normal diet (78.4 vs 94.6 %). Re-operation was
      undertaken in four patients after Nissen fundoplication (dysphagia, three; hiatus
      hernia, one) vs three after anterior 90 degrees  fundoplication (recurrent
      reflux, three). CONCLUSIONS: At 5 years, anterior 90 degrees  partial
      fundoplication was associated with less side effects, offset by greater use of
      antisecretory medication. Reflux symptoms and overall satisfaction were similar
      to Nissen fundoplication. Laparoscopic anterior 90 degrees  partial
      fundoplication is an effective treatment for gastro-esophageal reflux.

PMID- 22639378
TI  - Oxidative trifluoromethylthiolations of aryl boronic acids using a copper/O2
      based protocol.

PMID- 22639377
TI  - High expression of CX3CL1/CX3CR1 axis predicts a poor prognosis of pancreatic
      ductal adenocarcinoma.
AB  - BACKGROUND: CX3CL1 is a member of the chemokine family, and its receptor, CX3CR1,
      is expressed in pancreatic ductal adenocarcinoma. However, it is unclear whether
      there is a correlation between the expression of CX3CL1/CX3CR1 axis and the
      prognosis of patients with pancreatic ductal adenocarcinoma. METHODS: Tissue
      microarray and immunohistochemistry were used to study the expression of CX3CL1
      and CX3CR1 in 105 specimens of pancreatic ductal adenocarcinoma. We analyzed a
      relationship between patients' clinicopathological parameters and overall
      survival to the expression level of the CX3CL1/CX3CR1 axis using standard
      statistical analysis. RESULTS: The expression of CX3CL1 and CX3CR1 (77.1 and 66.7
      %, respectively) was clearly increased in areas of malignancy compared with
      peritumoral areas. We did not find any correlation between CX3CL1 and CX3CR1
      expression with clinical or pathological data. Patients' overall survival was
      clearly worse with the combined high expression of CX3CL1 and CX3CR1. Patients
      with a high CX3CL1 expression tumor had a significantly shorter overall survival.
      High CX3CR1 expression was an independent negative prognosis factor. CONCLUSION:
      We propose that the expression level of CX3CL1/CX3CR1 axis could provide clinical
      prognostic value, and the next steps should be to further investigate the
      mechanism by which CX3CL1 and its receptor impact survival in pancreatic ductal
      adenocarcinoma.

PMID- 22639379
TI  - Tissue-based risk assessment of cyclic volatile methyl siloxanes.
AB  - Cyclic volatile methyl siloxanes (cVMS) are important consumer materials that are
      used in personal care products and industrial applications. These compounds have
      gained increased attention in recent years following the implementation of
      chemical legislation programs worldwide. Industry-wide research programs are
      being conducted to characterize the persistence, bioaccumulation, and toxicity
      (PBT) properties of cVMS materials. As part of this larger effort, a tissue-based
      risk assessment was performed to further inform the regulatory decision-making
      process. Measured tissue concentrations of cVMS compounds in fish and benthic
      invertebrates are compared with critical target lipid body burdens (CTLBBs) as
      estimated with the target lipid model (TLM) to evaluate risk. Acute and chronic
      toxicity data for cVMS compounds are compared with data for nonpolar organic
      chemicals to validate application of the TLM in this effort. The analysis was
      extended to estimate the contribution from metabolites to the overall cVMS
      derived tissue residues using a food chain model calibrated to laboratory and
      field data. Concentrations of cVMS materials in biota from several trophic levels
      (e.g., invertebrates, fish) are well below the estimated CTLBBs associated with
      acute and chronic effects. This analysis, when combined with the limited
      biomagnification potential for cVMS compounds that was observed in the field,
      suggests that there is little risk of adverse effects from cVMS materials under
      present-day emission levels.

PMID- 22639380
TI  - Fluorescent protein engineering by in vivo site-directed mutagenesis.
AB  - In vivo site-directed mutagenesis by single-stranded deoxyribonucleic acid
      recombineering is a facile method to change the color of fluorescent proteins
      (FPs) without cloning. Two different starting alleles of GFP were targeted for
      mutagenesis: gfpmut3* residing in the Escherichia coli genome and egfp carried by
      a bacterial/mammalian dual expression lentiviral plasmid vector. Fluorescent
      protein spectra were shifted by subtle modification of the chromophore region and
      residues interacting with the chromophore of the FP. Eight different FPs
      (Violeta, Azure, Aqua, Mar, Celeste, Amarillo, Mostaza, and Bronze) were isolated
      and shown to be useful in multicolor imaging and flow cytometry of bacteria and
      transgenic human stem cells. To make in vivo site-directed mutagenesis more
      efficient, the recombineering method was optimized using the fluorescence change
      as a sensitive quantitative assay for recombination. A set of rules to simplify
      mutant isolation by recombineering is provided.

PMID- 22639381
TI  - Synthesis and Biological Activities of Some 1,3-Benzoxazol-2(3H)-One Derivatives
      as Anti-Quorum Sensing Agents.

PMID- 22639382
TI  - What are the unique and interacting contributions of school and family factors to
      early adolescents' empathic concern and perspective taking?
AB  - Empathy in children has received considerable attention in the literature, but
      limited research has investigated the contributions of various socializing
      factors on both affective (e.g., empathic concern) and cognitive (e.g.,
      perspective taking) components of empathy in early adolescents. Guided by
      socialization theories, this study examined the unique and interacting
      contributions of school connectedness and parent-child conflict to subsequent
      levels of both components of empathy across a 1-year period of time. Participants
      were 487 10- to 14- year old middle school students (54 % female; 76 % European
      American) involved in two waves of a study with 1 year between each wave.
      Hierarchical regression analyses indicated that, among girls, reports of parent
      child conflict contributed to a decrease in empathic concern one year later,
      whereas school connectedness was a protective factor that offset the negative
      impact of parent-child conflict on girls' subsequent perspective taking.
      Alternatively, only boys' reports of school connectedness contributed to
      subsequent increases in both empathic concern and perspective taking 1 year
      later. Findings indicate that school connectedness and conflict with parents play
      different socializing roles for girls' and boys' empathic concern and perspective
      taking. The current study calls for further research and youth programs to
      consider the important contributions that socializing agents can make on both
      components of empathy for early adolescent girls and boys.

PMID- 22639383
TI  - Zinc supplementation attenuates high glucose-induced epithelial-to-mesenchymal
      transition of peritoneal mesothelial cells.
AB  - Zinc (Zn) plays an important role in preventing many types of epithelial-to
      mesenchymal transition (EMT)-driven fibrosis in vivo. But its function in the EMT
      of the peritoneal mesothelial cells (PMCs) remains unknown. Here, we studied the
      Zn effect on the high glucose (HG)-induced EMT in the rat PMCs (RPMCs) and the
      underlying molecular mechanisms. We found that Zn supplementation significantly
      inhibited TGF-beta1 and ROS production, and attenuated the HG-induced EMT in the
      RPMCs, likely through inhibition of MAPK, NF-kappaB, and TGF-beta/Smad pathways.

PMID- 22639384
TI  - Bioavailability of trace elements in beans and zinc-biofortified wheat in pigs.
AB  - The objectives of this experiment were to study bioavailability of trace elements
      in beans and wheat containing different levels of zinc and to study how the water
      solubility of trace elements was related to the bioavailability in pigs. Three
      wheat and two bean types were used: wheat of Danish origin as a control (CtrlW),
      two Turkish wheat types low (LZnW) and high (HZnW) in zinc, a common bean (Com),
      and a faba bean (Faba). Two diets were composed by combining 81 % CtrlW and 19 %
      Com or Faba beans. Solubility was measured as the trace element concentration in
      the supernatant of feedstuffs, and diets incubated in distilled water at pH 4 and
      38 degrees C for 3 h. The bioavailability of zinc and copper of the three wheat
      types and the two bean-containing diets were evaluated in the pigs by collection
      of urine and feces for 7 days. The solubility of zinc was 34-63 %, copper 18-42
      %, and iron 3-11 %. The zinc apparent digestibility in pigs was similar in the
      three wheat groups (11-14 %), but was significantly higher in the CtrlW+Faba
      group (23 %) and negative in the CtrlW+Com group (-30 %). The apparent
      digestibility of copper was higher in the HZnW (27 %) and CtrlW+Faba (33 %)
      groups than in the CtrlW (17 %) and LZnW (18 %) groups. The apparent copper
      digestibility of the CtrlW+Com diet was negative (-7 %). The solubility and
      digestibility results did not reflect the concentration in feedstuffs. The in
      vitro results of water solubility showed no relationship to the results of trace
      mineral bioavailability in pigs.

PMID- 22639385
TI  - Antioxidant and antitumor activities of selenium- and zinc-enriched oyster
      mushroom in mice.
AB  - Selenium and zinc are well-known essential trace elements with potent biological
      functions. However, the possible health benefits of the combined administration
      of dietary selenium and zinc have not been studied extensively. In this study, we
      prepared selenium- and zinc-enriched mushrooms (SZMs) containing increased levels
      of selenium and zinc. The effects of SZMs on antioxidant and antitumor activities
      were evaluated. Mice were fed with either a control diet or a diet supplemented
      with SZMs or sodium selenite and zinc sulfate for 6 weeks. Antioxidant capacity
      was investigated by measuring the activities of antioxidant enzymes and the
      levels of lipid peroxide products. Results showed that treatment with SZMs
      significantly increased the activities of glutathione peroxidase (GPx) and
      superoxide dismutase and decreased the levels of malondialdehyde and lipofuscin.
      Furthermore, using a mouse model of lung tumors, we found that SZMs significantly
      decreased the number of tumor nodes with an increase in the activity of GPx. SZMs
      had a greater effect on the increase in both antioxidant and antitumor activities
      than did sodium selenite and zinc sulfate. These findings suggest that SZMs may
      be effective for improving antioxidant capacity and preventing tumors.

PMID- 22639386
TI  - Disrupted iron metabolism and ensuing oxidative stress may mediate cognitive
      dysfunction induced by chronic cerebral hypoperfusion.
AB  - Iron is a highly reactive free radical catalyst that has been shown to exacerbate
      oxidative stress and cell death in many neurodegenerative diseases. In this
      study, we produced a rat model of chronic cerebral hypoperfusion (CCH) by
      permanent bilateral carotid artery occlusion to investigate markers of iron and
      oxidative stress associated with it. We found CCH led to significant spatial
      memory impairment in the Morris water maze at 4 months after bilateral ligation.
      Iron deposition was observed in both the hippocampal CA1 area and cerebral
      cortex, and was correlated with localized neuronal death and increased lipid
      peroxidation. Western blotting revealed that the expression levels of ferritin
      heavy chain and the transferrin receptor were significantly elevated in
      hippocampus and cortex after CCH, whereas expression of iron regulatory protein 1
      was significantly lower than in sham-treated rats. We conclude that localized
      neurodegeneration and concomitant cognitive impairments following CCH may result,
      at least in part, from local disruption of neuronal iron metabolism.

PMID- 22639387
TI  - A comparison of washing methods for hair mineral analysis: internal versus
      external effects.
AB  - A major difficulty in hair elemental (mineral) analysis for biomonitoring is
      adequate understanding of the effectiveness of washing procedures. A review of
      washing protocols used in hair analysis publications showed little consensus with
      regard to solvents and surfactants used, washing times, and number of washing
      stages. Two washing approaches were subsequently used to compare their influence
      on internal and external surface elemental signals determined with time-of-flight
      secondary ion mass spectrometry. Na, K, Ca, Mg, and Fe were assessed with regard
      to their relative signal compared to carbon. Both washing methods had similar
      effect. All elements except for Fe appear to be removed from the surface of the
      hair as well as from inside the hair. Only the internal Fe content changed with
      washing and could indicate that external surface bound Fe may not be removed with
      most washing procedures. It is shown that washing procedures can have a
      significant effect on reducing the internal elemental signal levels in hair.

PMID- 22639389
TI  - Isostructural M2L4 molecular capsules with anthracene shells: synthesis, crystal
      structures, and fluorescent properties.
AB  - An isostructural series of M(2)L(4) molecular capsules quantitatively self
      assembled from two M(II) ions (M=Zn, Cu, Pt, Pd, Ni, Co, and Mn) and four bent
      ligands with embedded anthracene fluorophores. X-ray crystallographic analysis
      (for M=Zn, Cu, Ni, and Pd) confirmed the formation of closed-shell structures in
      which the large interior cavities inside the molecular capsules (about 1 nm) were
      shielded by eight anthracene panels. Analysis of the Zn(II) and Cu(II) structures
      showed the inclusion of an unusual triad guest cluster; four MeCN molecules, one
      water molecule, and one CF(3)SO(3)(-) ion were located inside the cavities. Full
      characterization by NMR spectroscopy and MS (ESI-TOF) demonstrated that the
      molecular capsules were quite stable and persist in solution. The fluorescence
      properties of the isostructural capsules were strongly dependent on the identity
      of the metal species: the Zn(II) capsule emitted strong blue fluorescence with a
      high quantum yield (Phi=0.8), in sharp contrast to the weakly emissive Ni(II) and
      Mn(II) capsules and the completely non-emissive Pd(II), Pt(II), and Co(II)
      capsules. On the other hand, the Cu(II) capsule exhibited solvatochromism and
      solvent-dependent emission behavior; blue emission of the capsule was "on" in
      DMSO but "off" in MeCN.

PMID- 22639388
TI  - ILF-3 is a regulator of the neural plate border marker Zic1 in chick embryos.
AB  - BACKGROUND: The neural crest is a multipotent cell type unique to the vertebrate
      lineage and capable of differentiating into a large number of varied cell types,
      including ganglia of the peripheral nervous system, cartilage, and glia. An early
      step in neural crest specification occurs at the neural plate border, a region
      defined by the overlap of transcription factors of the Zic, Msx, and Pax
      families. RESULTS: Here we identify a novel chick gene with close homology to
      double-stranded RNA-binding protein Interleukin enhancer binding factor 3 (ILF-3)
      in other species. Our results show that chick Ilf-3 is required for proper
      expression of the transcription factor, Zic-1, at the neural plate border.
      CONCLUSION: We have identified a novel chick gene and show it has a role in the
      correct specification of Zic-1 at the neural plate border.

PMID- 22639390
TI  - Liver transplantation for Alagille syndrome: the jagged edge.

PMID- 22639391
TI  - The biochemiresistor: an ultrasensitive biosensor for small organic molecules.
AB  - New sensation: A resistance-based biosensor uses gold-coated magnetic
      nanoparticles (Au@MNPs) functionalized with the antibiotic enrofloxin (see
      picture; purple), which bind to anti-enrofloxin as analyte (blue). The Au@MNPs
      can be magnetically assembled between electrodes, and the measured resistance R
      is a function of analyte concentration.

PMID- 22639392
TI  - The stigma scale for chronic illnesses 8-item version (SSCI-8): development,
      validation and use across neurological conditions.
AB  - BACKGROUND: Although the impact of stigma has been highlighted for epileptic
      populations, the experiences of people living with other neurological conditions
      have been less studied. PURPOSE: In order to promote research on stigma among
      people with neurological conditions, we sought to develop and psychometrically
      validate an eight-item questionnaire measuring internalised and enacted stigma
      experienced by people with epilepsy, multiple sclerosis (MS), Parkinson's disease
      (PD), stroke and amyotrophic lateral sclerosis (ALS). METHOD: We used item
      response theory methodologies to select items and field tested our items with 587
      participants from eight academic medical centres across the USA. RESULTS: We
      conducted exploratory and confirmatory factor analysis as well as examined the
      scale's reliability and validity. In addition, we conducted an analysis of
      variance test to examine mean total score differences across the five
      neurological conditions. Data from people across conditions revealed that the
      shortened instrument conformed to an essentially unidimensional model of
      multifaceted stigma as a one-factor questionnaire with correlated residuals on a
      pair of items that distinctly measured internalised stigma. CONCLUSION:
      Preliminary evidence suggests that the Stigma Scale for Chronic Illness 8-item
      version fits a unidimensional model, which assesses enacted and internalised
      stigma, and has adequate internal consistency/reliability and validity in
      relation to psychological distress and patient performance. Our results suggest
      fairly low stigma for neurological populations. In addition, our results suggest
      that stigma may be more severe for patients with ALS relative to those with MS
      and PD. In the future, the SSCI-8 scale could be used practically in clinic
      settings to examine stigma without the patient burden associated with lengthier
      scales.

PMID- 22639393
TI  - Vertical distribution of pharmaceuticals in lake sediments-citalopram as
      potential chemomarker.
AB  - The use of pharmaceuticals has increased enormously over the last few decades and
      serious concerns about their environmental fate and effects have arisen. Thus
      far, there is little knowledge about the historical pollution of the environment
      by pharmaceuticals. In the present study, sediment columns from three lake sites
      adjacent to wastewater treatment plants were collected, further divided in 2- or
      2.5-cm slices, and analyzed for 15 pharmaceuticals by liquid chromatography
      tandem mass spectrometry. In addition, sediment columns were historically
      interpreted by analyzing fecal sterols (coprostanol and cholesterol) as well as
      organic material and organic carbon. Several pharmaceuticals were detected in
      sediments, the most abundant being citalopram, bisoprolol, and propranolol. At
      site A, pharmaceuticals prevailed only in the uppermost 15 cm, whereas at site B
      they existed in the whole sediment column (0-30 cm). Pharmaceuticals were not
      found in site C sediments. Based on the sterol analyses, municipal wastewater
      contamination at sites A, B, and C was found in the uppermost 15, 30, and 20 cm,
      respectively. For the first time, contamination of sediments by pharmaceuticals
      was demonstrated below the subsurface (up to a depth of 30 cm). When considering
      the consumption and the observed concentration profiles of pharmaceuticals, a
      clear increasing trend of citalopram toward the surface was evident at site A.

PMID- 22639394
TI  - Second-generation supramolecular dendrimer with a defined structure due to
      orthogonal binding.
AB  - A second-generation supramolecular dendrimer has been prepared by orthogonal
      multiple hydrogen bonding. In the first (inner) recognition domain, the
      interaction of one bis-isocyanuric acid (25) with two branching units (21) that
      carry complementary Hamilton receptors has been exploited. In the second (outer)
      generation, the two ADDA (A=hydrogen-bond acceptor, D=donor) receptors of each
      branching unit (21) have bound complementary DAAD units (4). The problem of
      limited solubility of the building blocks has been overcome by the introduction
      of branched ethylhexyl residues and by the use of flexible alkylene or
      oligo(ethylene glycol) linking chains. The orthogonal binding of the two hydrogen
      bonding pairs was elucidated by chemical induced shift NMR titrations, which
      proved that the two pairs, isocyanuric acid with the Hamilton receptor and ADDA
      with DAAD, bind preferentially. The formation of the supramolecular self
      assembled 1:2:4 dendrimer with a molecular weight of 5065 g mol(-1) was
      investigated by diffusion NMR spectroscopy.

PMID- 22639395
TI  - Levothyroxine medication is associated with adiposity independent of TSH.
AB  - AIM: In euthyroidism, higher TSH levels are weakly associated with increased BMI.
      Furthermore, a considerable number of patients complain of weight gain during
      thyroid hormone replacement after thyroidectomy. We therefore investigated the
      association between levothyroxine medication and BMI in a large cross-sectional
      study group. METHODS: We included euthyroid participants from the MeSyBePo study
      group (TSH between 0.3 and 4.5 MUU/ml) that did not take thyreostatic drugs.
      Linear regression analyses were performed to address the association between
      levothyroxine medication and obesity. Additionally, pairs matched by sex, age and
      TSH but discordant in levothyroxine medication were compared. RESULTS: 1663
      subjects (569 males) were eligible for inclusion. 151 participants were taking
      levothyroxine. Adjusted for sex and age both TSH (standardised beta 0.1, p<0.001)
      and levothyroxine medication (standardised beta 0.05, p=0.03) were significantly
      associated with BMI. There was no significant interaction between TSH and
      levothyroxine medication with respect to BMI. Further adjustment for smoking and
      the restriction to those subjects with normal glucose metabolism (947
      participants (314 males, 82 on levothyroxine medication) did not alter the
      result. In matched pair analysis (133 pairs), BMI was significantly increased in
      subjects taking levothyroxine compared to controls. CONCLUSION: Independently
      from TSH, levothyroxine medication was associated with a higher BMI. The
      mechanisms, however, responsible for this association need to be elucidated.

PMID- 22639396
TI  - Relations among glycemic control, circulating endothelial cells, nitric oxide,
      and flow mediated dilation in patients with type 2 diabetes mellitus.
AB  - OBJECTIVES: Circulating endothelial cells (CEC) have been identified as a
      surrogate marker of endothelial dysfunction. The aim of this study was to
      determine the association of glycemic control with CEC and endothelial function
      in patients with type 2 diabetes mellitus (DM). METHODS: We studied 30 patients
      with type 2 DM and 20 age and sex matched healthy controls (HC). Number of
      circulating endothelial cells was measured by flow cytometry. Endothelial
      function was studied by measuring flow mediated vasodilation (FMD%) in the
      brachial artery and serum level of nitric oxide (NO). RESULTS: CEC count was
      significantly elevated in patients with DM, than HC (35.3+/-15.1 vs. 7.3+/-2.4,
      p<0.001) and in patients with HbA1c>7 than patients with HbA1c<=7 (47.4+/-5.5 vs.
      19.5+/-5.7, p<0.001). FMD% and NO were lower in DM patients than HC (3.5+/-0.85
      vs. 9.5+/-3.1, p<0.001 and 37.8+/-6.1 vs. 64.1+/-5.7, p<0.001 respectively). FMD%
      and NO were lower in patients with HbA1c>7 as compared to patients with HA1c<=7
      (2.8+/-0.4 vs. 4.3+/-0.4, p<0.001 and 33.1+/-2.9 vs. 43.9+/-2.8, respectively,
      p<0.001). HbA1c correlated negatively with FMD% and NO levels and positively with
      CEC. CEC count correlated negatively with FMD% and NO. There was a significant
      positive correlation between CEC count and HBA1c (p<0.001 for all correlations).
      CONCLUSION: CEC is associated with markers of endothelial dysfunction and disease
      control in patients with type 2 DM. These findings suggest a potential role of
      CEC in the pathophysiology of cardiovascular disease in type 2 diabetic and raise
      the importance of tight glycemic control.

PMID- 22639397
TI  - Statin is a reasonable treatment option for patients with Polycystic Ovary
      Syndrome: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVES: To date no consensus has been reached on whether to administer statin
      to patients with Polycystic Ovary Syndrome (PCOS) routinely. Therefore, we
      conduct a meta-analysis to synthesize the literatures regarding therapeutic
      effects of statins on PCOS. METHODS: A comprehensive literature search was
      performed using terms such as polycystic ovary syndrome, ovary polycystic
      disease, PCOS, hyperandrogaenemia; simvastatin, atorvastatin, lipidemic
      modulating drugs, lipid lowering drugs, and testosterone; randomized controlled
      trials in the following bibliographic databases: Medline, Embase, Cochrane
      Controlled Trials Register. Identified reference lists were checked manually.
      RESULTS: In total, 4 RCTs were included. 3 of 4 studies were double-blinded while
      none reported whether of the data was analyzed using intention-to-treat analysis.
      Serum total testosterone and lipid profiles were included as investigation
      outcomes. Differences in reducing serum total testosterone were observed when
      comparing statin with placebo (Std MD= - 3.03, 95%CI - 5.85 ~ - 0.22, P=0.03) or
      statin + metformin with metformin (Std MD=- 1.07, 95%CI: - 2.06~ - 0.07, P=0.04).
      Heterogeneities were detected in both comparisons (I2=96% and 88% respectively).
      Meanwhile, statin was more effective than placebo in reducing LDL (WMD=- 0.87,
      95%CI - 1.18~ - 0.55, P<0.0001), TC (WMD=- 1.23 95%CI - 1.35~ - 1.11, P<0.00001),
      TG (WMD= - 0.50, 95%CI - 0.73~ - 0.27, P<0.00001); and statin + metformin was
      more effective than metformin in lowering LDL (WMD= - 0.84, 95%CI: - 1.33 ~ -
      0.354, P=0.0009), TC (WMD= - 1.28, 95%CI: - 1.47 ~ - 1.10, P<0.00001), and TG
      (WMD= - 0.27, 95%CI: - 0.36~ - 0.19, P<0.00001). Heterogeneities were detected
      during the meta-analysis. CONCLUSIONS: Statins can reduce the concentration of
      total testosterone, TC, TG and LDL. However, it cannot be concluded that statins
      have long-term benefit. A large-scale, randomized controlled study is needed to
      ascertain this uncertainty.

PMID- 22639398
TI  - HOMA-S is associated with greater HbA1c reduction with a GLP-1 analogue in
      patients with type 2 diabetes.
AB  - Exenatide, a glucagon-like peptide-1 (GLP-1) analogue, is an effective
      glucoregulator for treating overweight individuals, not at target HbA1 c. This
      prospective study aimed to determine whether estimates of beta cell function
      (HOMA-B) and insulin sensitivity (HOMA-S) predict response to Exenatide
      treatment.Prospective data on 43 type 2 diabetes patients were collected for up
      to 2.8 years in UK primary care. HOMA-B and HOMA-S were estimated prior to
      initiating Exenatide, with monitoring of cardio-metabolic risk factors.Mean (SD)
      age and BMI pre-treatment were 54.1+/-10.5 years and 35.7+/-7.5 kg/m2
      respectively. HbA1c decreased (mean reduction 0.9%, p=0.04; p for trend=0.01) in
      61% of patients. In univariate analyses, HOMA-S as a measure of insulin
      sensitivity was inversely (beta=- 0.41, p 0.009) related to change in HbA1c, with
      no relation for HOMA-B.In a random effects regression model that included age at
      baseline, weight, LDL-C, HDL-C and triglycerides, change in HbA1c (beta= - 0.14,
      p<0.001) and HDL-C (beta= - 0.52, p=0.011) were independently associated with
      increasing insulin sensitivity (r2=0.52). Thus patients with greater measured
      insulin sensitivity achieved greater reduction in HbA1c independent of the
      factors described above.In logistic regression those in the highest tertile of
      log-HOMA-S were 45% more likely to have a fall in HbA1c with an odds ratio (OR)
      of 0.55 (95% CI 0.47-0.66) p<0.0001 (log likelihood ratio for the model
      chi2=71.6, p<0.0001).Patients with greater measured insulin sensitivity achieve
      greater reduction in HbA1c with Exenatide. Determination of insulin sensitivity
      may assist in guiding outcome expectation in overweight patients treated with GLP
      1 analogues.

PMID- 22639399
TI  - Effects of supervised exercise on gamma-glutamyl transferase levels in patients
      with isolated impaired fasting glucose and those with impaired fasting glucose
      plus impaired glucose tolerance.
AB  - AIM: To study the effects of a supervised exercise program on serum gamma
      glutamyl transferase (GGT), glycemic control and cardiovascular risk factors in
      pre-diabetic patients with isolated impaired fasting glucose (IFG) and those with
      IFG plus impaired glucose tolerance (IGT). METHODS: Out of 60 pre-diabetic
      patients (30 with isolated IFG and 30 with IFG + IGT) 24 were randomly assigned
      to the supervised exercise program (1 h twice a week) and 36 only obtained
      counselling on the risk of diabetes and its prevention. Patients have been
      followed over a 12-month period. RESULTS: The main findings were that patients
      with IFG + IGT had increased GGT levels at baseline (49.2+/-27.4 U/L) compared to
      subjects with isolated IFG (28.1+/-21.9 U/L) (p<0.01), and that GGT levels
      improved only after the supervised exercise intervention within the IFG + IGT
      subjects ( - 17.7+/-19.6 U/L). Similarly, baseline triglyceride levels were also
      higher in IFG + IGT patients (p<0.001) and there was a decrease through exercise
      intervention in these patients only (p<0.05). CONCLUSION: GGT is an unspecific
      marker of oxidative stress and both high plasma glucose and triglycerides levels
      may produce oxidative stress. Thus, patients with IFG + IGT seem to have higher
      levels of oxidative stress than those with isolated IFG. Based on the known
      association between GGT levels and cardiovascular risk factors, IFG + IGT
      patients may be at higher risk for the development of cardiovascular diseases.
      The specific effect of regular exercise on GGT in pre-diabetic patients may
      contribute to the understanding of the preventive effects related to exercise.

PMID- 22639400
TI  - The rhPTH (1-34), but not elcatonin, increases bone anabolic efficacy in
      postmenopausal women with osteoporosis.
AB  - PURPOSE: Intermittent administration of recombinant human PTH [rhPTH (1-34)]
      exerts an osteoanabolic effect characterized by direct effects on bone formation,
      increases bone density, and reduces fracture risk. This study was to investigate
      the anabolic effects of rhPTH(1-34) on postmenopausal osteoporosis in an Asian
      population and compare the time course and alteration in bone turnover marker
      (BTM) during rhPTH(1-34) and elcatonin treatment. METHODS: 124 women with
      postmenopausal osteoporosis were enrolled in this prospective, open-label, active
      controlled trial. The patients randomized to subcutaneous rhPTH(1-34) (20 ug,
      once daily) or elcatonin (200U, once week) injections for 12 months. Biochemical
      markers of bone formation (bone specific alkaline phosphatase [BSAP]), and bone
      resorption maker (serum C-telopeptide of type I collagen [CTX-I] were measured at
      baseline and at 0, 6, and 12 months. RESULTS: At 12 months, rhPTH (1-34)
      significantly increased lumbar spine BMD significantly compared with baseline,
      whereas elcatonin was ineffective. BSAP levels were gradually increased in almost
      all rhPTH(1-34)-treated subjects and at the end of the study, the percentage of
      subjects with BSAP above the postmenopausal reference interval was gradually
      increased as high as 91.5% at month 12. Opposite trends in percentages for CTX-I
      was observed in rhPTH(1-34). With rhPTH(1-34), but not elcatonin, there were
      significant positive correlations between ratio of BSAP and CTX-I and bone
      mineral density (BMD) (r=0.318) at the end of month 12. Both treatments were well
      tolerated and there were no significant differences detected between the 2 groups
      in the proportion of any adverse events and any serious adverse events.
      CONCLUSIONS: rhPTH (1-34) has more positive effects on bone formation than
      elcatonin for postmenopausal women with osteoporosis and was proved to be safe
      and well tolerated. The ratio of BSAP and CTX-I may be a useful indicator for
      positive bone formation.

PMID- 22639401
TI  - Sirolimus: more cause for alarm?

PMID- 22639402
TI  - The dissociative subtype of PTSD: a replication and extension.
AB  - BACKGROUND: The nature of the relationship between dissociation and posttraumatic
      stress disorder (PTSD) has clinical and nosological importance. The aim of this
      study was to evaluate the evidence for a dissociative subtype of PTSD in two
      independent samples and to examine the pattern of personality disorder (PD)
      comorbidity associated with the dissociative subtype of PTSD. METHODS: Latent
      profile analyses were conducted on PTSD and dissociation items reflecting
      derealization and depersonalization in two samples of archived data: Study 1
      included 360 male Vietnam War Veterans with combat-related PTSD; Study 2 included
      284 female Veterans and active duty service personnel with PTSD and a high base
      rate of exposure to sexual trauma. RESULTS: The latent profile analysis yielded
      evidence for a three-class solution in both samples: the model was defined by
      moderate and high PTSD classes and a class marked by high PTSD severity coupled
      with high levels of dissociation. Approximately 15% of the male sample and 30% of
      the female sample were classified into the dissociative class. Women (but not
      men) in the dissociative group exhibited higher levels of comorbid avoidant and
      borderline PD diagnoses. CONCLUSIONS: Results provide support for a dissociative
      subtype of PTSD and also suggest that dissociation may play a role in the
      frequent co-occurrence of PTSD and borderline PD among women. These results are
      pertinent to the on-going revisions to the DSM and suggest that consideration
      should be given to incorporating a dissociative subtype into the revised PTSD
      criteria.

PMID- 22639403
TI  - Carbonization and activation of inexpensive semicoke-packed electrodes to enhance
      power generation of microbial fuel cells.
AB  - A simple and low-cost modification method was developed to improve the power
      generation performance of inexpensive semicoke electrode in microbial fuel cells
      (MFCs). After carbonization and activation with water vapor at 800-850  degrees
      C, the MFC with the activated coke (modified semicoke) anode produced a maximum
      power density of 74 Wm(-3) , 17 Wm(-3) , and 681 mWm(-2) (normalized to anodic
      liquid volume, total reactor volume, and projected membrane surface area,
      respectively), which was 124 % higher than MFCs using a semicoke anode (33 Wm(-3)
      , 8 Wm(-3) , and 304 mWm(-2) ). When they were used as biocathode materials,
      activated coke produced a maximum power density of 177 Wm(-3) , 41 Wm(-3) , and
      1628 mWm(-2) (normalized to cathodic liquid volume, total reactor volume, and
      projected membrane surface area, respectively), which was 211 % higher than that
      achieved by MFCs using a semicoke cathode (57 Wm(-3) , 13 Wm(-3) , and 524 mWm(
      2) ). A substantial increase was also noted in the conductivity, C/O mass ratio,
      and specific area for activated coke, which reduced the ohmic resistance,
      increased biomass density, and promoted electron transfer between bacteria and
      electrode surface. The activated coke anode also produced a higher Coulombic
      efficiency and chemical oxygen demand removal rate than the semicoke anode.

PMID- 22639404
TI  - An iron(III) iodosylbenzene complex: a masked non-heme Fe(V)O.

PMID- 22639405
TI  - Paternal dietary restriction affects progeny fat content in Caenorhabditis
      elegans.
AB  - Epidemiological data from human populations and few reports in rodents suggested
      that the paternal diet affects offspring adiposity and its related diseases. We
      tested whether this nongenetic and intergenerational inheritance depends on
      paternal treatment dose. Using the model organism Caenorhabditis elegans, males
      undergoing several dietary restriction regimes were crossed with ad libitum fed
      females. We found an inverted U-shaped relationship between the extent of
      paternal dietary restriction and the level of fat content of progeny. The
      relationship was evident in both sexes. Body proportions were not affected in
      offspring. Overall, our findings extent the concept of developmental and adaptive
      plasticity to include the extent of paternal food consumption in the origin of
      phenotypic alterations.

PMID- 22639406
TI  - Use of matrix assisted laser desorption ionisation-time of flight mass
      spectrometry in a paediatric clinical laboratory for identification of bacteria
      commonly isolated from cystic fibrosis patients.
AB  - BACKGROUND: Matrix-assisted laser desorption ionisation-time of flight mass
      spectrometry (MALDI-TOF MS) has been described as a rapid, accurate method for
      bacterial identification. AIMS: To investigate the ability of the technique,
      using the unamended database supplied with the system, to identify bacteria
      commonly isolated in cystic fibrosis (CF) patients. METHODS: Organisms commonly
      isolated from CF patients identified by MALDI-TOF MS were compared to
      conventional phenotypic and genotypic analyses. For MALDI-TOF MS, the direct
      colony technique was used routinely with one extraction procedure performed on a
      mucoid Pseudomonas aeruginosa. For 24 unique CF specimens, workload comparison
      and time to identification were assessed. RESULTS: Of 464 tested isolates,
      conventional (phenotypic and genotypic) identification compared to MALDI-TOF MS
      showed complete genus, species agreement in 92%, with genus agreement in 98%.
      This included 29 isolates within the Burkholderia cepacia complex. All 29 were
      correctly identified to the genus level and 24 of these were speciated. Time to
      identification with 47 bacterial isolates from 24 CF patients showed
      identification of 85% of isolates by MALDI-TOF MS at 48 h of incubation, compared
      to only 34% with conventional methods. CONCLUSIONS: Using the unamended database
      supplied with the system, MALDI-TOF MS provides rapid and reliable identification
      of bacteria isolated from CF specimens. Time to identification studies showed
      that the use of same day, same method for organism identification will decrease
      time to result and optimise microbiology workflow.

PMID- 22639408
TI  - Twisted gastrulation expression in cholangiocellular and hepatocellular
      carcinoma.
AB  - AIMS: To assess the expression of Twisted gastrulation (TWSG1) protein, which
      regulates the activity of bone morphogenetic proteins (BMPs) in the extracellular
      space in malignant epithelial tumours of the liver. METHODS: Thirteen
      hepatocellular carcinoma (HCC) samples and 12 intrahepatic cholangiocellular
      carcinoma (CCA) samples were compiled into diagnosis-specific tissue microarrays.
      Sections were immunostained with a monoclonal antibody against TWSG1 and a
      polyclonal antibody against BMP4. Human cell lines were also used, including one
      HCC cell line (HepG2), three CCA cell lines (OZ, Huh-28, HuCCT-1) and a Papova
      immortalised normal hepatocyte cell line (THLE-3) for western blot analysis
      (WBA). RESULTS: Immunostaining and WBA showed a stronger TWSG1 expression in CCA
      than in HCC. The difference in expression was significant (p<0.05), and the
      immunohistochemical signal was particularly evident in the malignant epithelial
      areas close to desmoplastic stroma in CCA and in the areas of glandular
      differentiation in HCC. No expression was seen in normal hepatocytes.
      Interestingly, BMP4 was fully expressed in CCA and only partly in HCC. WBA showed
      a band for BMP4 in both CCA and HCC cell lines. CONCLUSIONS: TWSG1 is expressed
      in both malignant epithelial carcinomas, although the level of expression is
      higher in CCA than in HCC and seems to correlate at least partially with BMP4
      expression.

PMID- 22639407
TI  - PTEN deletion is rare but often homogeneous in gastric cancer.
AB  - BACKGROUND AND AIM: Gastric carcinoma is the second most frequent cause of cancer
      related death worldwide. As PTEN is a potential modifier of tumour response to
      trastuzumab, a recently approved therapy in metastatic HER2 positive gastric
      cancer, the existence of PTEN deletions in primary gastric cancer was
      investigated. METHODS: 230 primary gastric cancers were analysed in a tissue
      microarray format by dual labelling fluorescence in situ hybridisation for PTEN
      deletion. HER2 analysis was also performed. To study PTEN deletion heterogeneity,
      all available large tissue sections from primary cancer and corresponding
      metastases were analysed in seven patients. RESULTS: Eight of 180 interpretable
      primary gastric cancer spots showed PTEN deletions (4.4%), including seven
      hemizygous and one homozygous deletion. PTEN deletion was correlated with nodal
      (8 of 122 cases (6.6%); p=0.041) and distant metastases (4 of 19 (21.1%);
      p<0.001). Large section validation showed a homogeneous distribution of PTEN
      deletion. HER2 positivity was seen in one PTEN deleted case. CONCLUSION: Genomic
      PTEN deletion is a rare event in gastric adenocarcinoma but correlates with
      metastatic disease. The homogeneous distribution pattern indicates that this
      alteration occurs early in tumour development.

PMID- 22639409
TI  - Trends of stage, grade, histology and tumour necrosis in renal cell carcinoma in
      a European centre surgical series from 1984 to 2010.
AB  - AIMS: To analyse renal cell carcinoma (RCC) stage, grade, histology and necrosis
      migration in a large European centre series over the last 27 years. METHODS: The
      pathology reports of 2739 consecutive patients with RCC who underwent nephrectomy
      from 1984 to 2010 at the institution of the authors were systematically re
      evaluated. Patients were pooled into five time groups according to the date of
      surgery: group 1: 1984-1989, group 2: 1990-1994, group 3: 1995-1999, group 4:
      2000-2004 and group 5: 2005-2010, respectively. Changes in pT categories
      according to WHO 2010 classification, tumour grade, histological subtype and
      presence of tumour necrosis (TN) were evaluated. RESULTS: Small pT1a tumours were
      found in 62/485 (12.8%) and 312/639 (48.8%) patients in groups 1 and 5,
      respectively (p<0.001). Advanced tumour stages (pT3a-4) were found in 306/485
      (63.1%) and 171/639 (26.8%) patients in groups 1 and 5, respectively (p<0.001).
      The number of grade 3/4 tumours increased from 62/485 (12.7%) and 130/639 (20.3%)
      in groups 1 and 5, respectively, whereas the number of grade 1 tumours decreased
      over time (p<0.001). There has been a significant histological migration for the
      chromophobe subtype from 1.1% to 4.3% (p=0.002). The frequency of the presence TN
      decreased from 41.7% in group 1 to 32.7% in group 5 (p<0.001). CONCLUSIONS: In
      contrast to data from Australia but similar to data from US cohorts, a
      statistically significant stage migration towards small RCCs was observed in this
      European cohort. Significant changes in tumour grade, histological subtype and TN
      were also observed.

PMID- 22639410
TI  - Contaminant residues and declines of the Cascades frog (Rana cascadae) in the
      California Cascades, USA.
AB  - Populations of Cascades frogs (Rana cascadae) have declined precipitously in the
      Mount Lassen area, but remain abundant in the other half of their California
      range in the Klamath Mountains. To evaluate the role of contaminants in Cascade
      frog declines, we sampled sediment and frog tadpole tissue at 31 sites where
      Cascades frogs had disappeared and sites where Cascades frogs are still present
      across the Lassen and Klamath regions. Pacific chorus frogs (Pseudacris regilla)
      were tested and used as surrogates for residue concentrations in Cascades frogs.
      We analyzed a total of 79 tadpole samples for 73 semivolatile contaminants
      including pesticides, polychlorinated biphenyls (PCBs), and polycyclic aromatic
      hydrocarbons (PAHs). The most frequently detected residue was endosulfan sulfate,
      followed by dacthal, chlorpyrifos, PCB 187, endosulfan II, trans-chlordane, and
      trans-nonachlor. Chorus frogs had similar residue concentrations as Cascades
      frogs for most but not all chemicals, indicating that chorus frogs can serve as a
      reasonable proxy for chemical concentrations in Cascades frogs. None of the
      contaminants in tissue or sediment had significantly higher concentrations at
      sites where Cascades frogs have disappeared than at sites where Cascades frogs
      are still present. We found no evidence to support the hypothesis that the
      contaminants analyzed have contributed to the decline of Cascades frogs in
      northern California, although we were able to analyze only a handful of the over
      300 pesticides currently used in the area.

PMID- 22639411
TI  - Synthesis, coordination behavior, and reduction chemistry of cymantrenyl-1,3
      bis(2,3,4,5-tetraphenyl)borole.
AB  - We describe the synthesis of base-free bisborole [Cym(?)(BC(4)Ph(4))(2)]
      Cym(?)=(OC)(3)Mn(eta(5)-C(5)H(3))-and its transformation into two fully
      characterized Lewis acid-base adducts with pyridine bases of the type 4-R
      NC(5)H(4) (R=tBu, NMe(2)). The results of electrochemical, as well as NMR and
      UV/Vis spectroscopic studies on [Cym(?)(BC(4 Ph(4))(2)] and the related
      monoborole derivative [Cym(BC(4)Ph(4))]-Cym=(OC)(3)Mn(eta(5)-C(5) H(4))-provided
      conclusive evidence for 1) the enhanced Lewis acidity of the two boron centers
      that result from conjugation of two borole fragments, and 2) the fact that Mn-B
      bonding interactions between the Lewis acidic borole moieties and the Mn center
      are considerably less pronounced for bisborole [Cym(?)(BC(4)Ph(4))(2)]. In
      addition, the reduction chemistry of [Cym(?)(BC(4)Ph(4))(2)] has been studied in
      detail, both electrochemically and chemically. Accordingly, chemical reduction of
      [Cym(?)(BC(4)Ph(4))(2)] with magnesium anthracene afforded the corresponding
      tetraanion, which features a rare Mg-OC bonding mode in the solid state.

PMID- 22639412
TI  - Prognostic impact of off-hour liver transplants on graft and survival outcomes.

PMID- 22639413
TI  - Long-term follow-up of cancer patients treated with gene therapy medicinal
      products.
AB  - European Union requirements are discussed for the long-term follow-up of advanced
      therapy medicinal products, as well as how they can be applied to cancer patients
      treated with gene therapy medicinal products in the context of clinical trials,
      as described in a specific guideline issued by Gene Therapy Working Party at the
      European Medicine Agency.

PMID- 22639414
TI  - One-pot conversions of lignocellulosic and algal biomass into liquid fuels.
AB  - The one-pot conversion of lignocellulosic and algal biomass into a liquid fuel,
      2,5-dimethylfuran (DMF), has been achieved by using a multicomponent catalytic
      system comprising [DMA]+ [CH3SO3]- (DMA=N,N-dimethylacetamide), Ru/C, and formic
      acid. The synthesis of DMF from all substrates was carried out under mild
      reaction conditions. The reaction progressed via 5-hydroxyemthylfurfural (HMF) in
      the first step followed by hydrogenation and hydrogenolysis of HMF with the Ru/C
      catalyst and formic acid as a hydrogen source. This report discloses the
      effectiveness of the Ru/C catalyst for the first time for DMF synthesis from
      inexpensive and readily abundant biomass sources, which gives a maximum yield of
      32 % DMF in 1 h. A reaction route involving 5-(formyloxymethyl)furfural (FMF) as
      an intermediate has been elucidated based on the 1H and 13C NMR spectroscopic
      data. Another promising biofuel, 5-ethoxymethylfurfural (EMF), was also
      synthesized with high selectivity from polymeric carbohydrate-rich biomass
      substrates by using a Bronsted acidic ionic liquid catalyst, that is [DMA]+
      [CH3SO3]-, by etherification of HMF in ethanol.

PMID- 22639415
TI  - Periodate salts as pyrotechnic oxidizers: development of barium- and perchlorate
      free incendiary formulations.
AB  - In a flash: pyrotechnic incendiary formulations with good stabilities toward
      various ignition stimuli have been developed without the need for barium or
      perchlorate oxidizers. KIO(4) and NaIO(4) were introduced as pyrotechnic
      oxidizers and exhibited excellent pyrotechnic performance. The periodate salts
      may garner widespread use in military and civilian fireworks because of their low
      hygroscopicities and high chemical reactivities.

PMID- 22639417
TI  - Walking metals in d8...d8 hetero-bimetallic complexes: an original dynamic
      phenomenon.
AB  - In the course of our investigations on polymetallic complexes derived from 1,3
      bis(thiophosphinoyl)indene (Ind(Ph(2)P=S)(2)), we observed original fluxional
      behavior and report herein a joint experimental/computational study of this
      dynamic process. Starting from the indenylidene chloropalladate species
      [Pd{Ind(Ph(2) P=S)(2)}Cl](-) (1), the new Pd(II)...Rh(I) hetero-bimetallic pincer
      complex [PdCl{Ind(Ph(2) P=S)(2)}Rh(nbd)] (2; nbd=2,5-norbornadiene) was prepared.
      X-ray crystallography and DFT calculations substantiate the presence of a
      d(8)...d(8) interaction. According to multinuclear variable-temperature NMR
      spectroscopic experiments, the pendant {Rh(nbd)} fragment of 2 readily shifts in
      solution at room temperature between the two edges of the SCS tridentate ligand.
      To assess the role of the pincer-based polymetallic structure on this fluxional
      behavior, the related monometallic Rh complex [Rh{IndH(Ph(2) P=S)(2)}(nbd)] (3)
      was prepared. No evidence for a metal shift was observed in that case, even at
      high temperature, thus indicating that inplane pincer coordination to the Pd
      center plays a crucial role. The previously described Pd(II)...Ir(I) bimetallic
      complex 4 exhibited fluxional behavior in solution, but with a significantly
      higher activation barrier than 2. This finding demonstrates the generality of
      this metal-shift process and the strong influence of the involved metal centers
      on the associated activation barrier. DFT calculations were performed to shed
      light onto the mechanism of such metal-shift processes and to identify the
      factors that influence the associated activation barriers. Significantly
      different pathways were found for bimetallic complexes 2 and 4 on one hand and
      the monometallic complex 3 on the other hand. The corresponding activation
      barriers predicted computationally are in very good agreement with the
      experimental observations.

PMID- 22639416
TI  - Glucose-6-phosphate metabolism in Plasmodium falciparum.
AB  - Malaria is still one of the most threatening diseases worldwide. The high drug
      resistance rates of malarial parasites make its eradication difficult and
      furthermore necessitate the development of new antimalarial drugs. Plasmodium
      falciparum is responsible for severe malaria and therefore of special interest
      with regard to drug development. Plasmodium parasites are highly dependent on
      glucose and very sensitive to oxidative stress; two observations that drew
      interest to the pentose phosphate pathway (PPP) with its key enzyme glucose-6
      phosphate dehydrogenase (G6PD). A central position of the PPP for malaria
      parasites is supported by the fact that human G6PD deficiency protects to a
      certain degree from malaria infections. Plasmodium parasites and the human host
      possess a complete PPP, both of which seem to be important for the parasites.
      Interestingly, there are major differences between parasite and human G6PD,
      making the enzyme of Plasmodium a promising target for antimalarial drug design.
      This review gives an overview of the current state of research on glucose-6
      phosphate metabolism in P. falciparum and its impact on malaria infections.
      Moreover, the unique characteristics of the enzyme G6PD in P. falciparum are
      discussed, upon which its current status as promising target for drug development
      is based.

PMID- 22639418
TI  - Evaluation of long-term follow-up with neointimal coverage and stent apposition
      after sirolimus-eluting stent implantation by optical coherence tomography.
AB  - BACKGROUND: Late stent thrombosis related to delayed endothelialization is a
      major concern after drug-eluting stent (DES) implantation. The long-term vascular
      response towards DES implantation remains unclear. Optical coherence tomography
      (OCT) is a high-resolution imaging modality which provides new opportunities for
      evaluating neointimal coverage and stent strut apposition after stent
      implantation. METHODS: Fifty two patients who accepted 64 sirolimus-eluting
      stents (SESs, Cypher Select) were enrolled in the study. The OCT procedure was
      performed in 20 patients at 12 months (group 1), 17 patients at 24 months (group
      2), and 15 patients at 48 months (group 3) after SESs implantation, respectively.
      The neointimal hyperplasia (NIH) thickness and stent strut apposition were
      assessed at 1-mm interval, and the presence of thrombus was observed in each
      stent. RESULTS: The NIH thickness was significantly higher at 48 months than that
      of 12 months (0.1694 +/- 0.1455 mm in G3 vs. 0.1455 +/- 0.1373 mm in G1, P <
      0.01) and 24 months (0.1514 +/- 0.1296 mm in G2, P <0.01) after SESs
      implantation, but no significant difference existed between that of 12 months and
      24 months (P > 0.05). Longer follow-up time was associated with significant
      decrease in the prevalence of uncovered struts (17.3% in group 1 vs. 8.8% in
      group 2 vs. 2.6% in group 3, P < 0.01) and malapposed struts (14.2% in group 1
      vs. 10.3% in group 2 vs. 4.7% in group 3, P < 0.01). The incidence of
      intracoronary thrombus steadily decreased from 3.6% at 12 months to 2.4% at 24
      months, and to 0.8% at 48 months (P < 0.01). CONCLUSION: Neointimal growth
      continued for as long as 48 months after SES implantation. NIH thickness
      increased insignificantly from 12 to 24 months, but markedly increased at 48
      months after stent implantation. Late neointimal growth was accompanied by a
      higher rate of covered struts and lower rate of malapposed stent struts.

PMID- 22639420
TI  - Biomineralization as an inspiration for materials chemistry.
AB  - Living organisms are well known for building a wide range of specially designed
      organic-inorganic hybrid materials such as bone, teeth, and shells, which are
      highly sophisticated in terms of their adaptation to function. This has inspired
      physicists, chemists, and materials scientists to mimic such structures and their
      properties. In this Review we describe how strategies used by nature to build and
      tune the properties of biominerals have been applied to the synthesis of
      materials for biomedical, industrial, and technological purposes. Bio-inspired
      approaches such as molecular templating, supramolecular templating, organized
      surfaces, and phage display as well as methods to replicate the structure and
      function of biominerals are discussed. We also show that the application of in
      situ techniques to study and visualize the bio-inspired materials is of paramount
      importance to understand, control, and optimize their preparation. Biominerals
      are synthesized in aqueous media under ambient conditions, and these approaches
      can lead to materials with a reduced ecological footprint than can traditional
      methods.

PMID- 22639419
TI  - Clinical factors predicting readmission after orthotopic liver transplantation.
AB  - Hospitals with the highest readmission rates for high-cost conditions may be
      targeted for payment penalties. The primary aim of this study was to determine
      clinical predictors of 30-day readmission after discharge for patients undergoing
      orthotopic liver transplantation (OLT) at the University of Washington from
      January 2003 to October 2010. Secondary aims included the determination of
      predictors of institutional care after OLT and differences in survival between
      patients requiring 30-day readmission and patients not requiring 30-day
      readmission. Sixty-five of 766 discharged OLT patients (8.6%) required
      institutional care on discharge; 318 of the 701 remaining patients (45%) were
      readmitted within 30 days. The predictors of readmission included hospitalization
      within the 90 days before OLT [29.6% versus 18.4%, relative risk (RR) = 1.33, P =
      0.04], pre-OLT portal vein thrombosis (7.9% versus 4.4%, RR = 1.76, P = 0.01), a
      creatinine level > 1.9 mg/dL (23.9% versus 11.5%, RR = 2.1, P <= 0.01), an
      albumin level < 2.6 mg/dL (51.9% versus 37.6%, RR = 1.57, P < 0.01),
      postoperative complications (38.7% versus 30.2%, RR = 1.31, P = 0.04), and a high
      school education or less (14.5% versus 10%, RR = 1.41, P = 0.04). One year after
      OLT, decreased survival was found for patients requiring 30-day readmission
      versus patients not requiring readmission (88.2% versus 95.6%, P < 0.05). In
      conclusion, this study has identified patients at high risk of readmission who
      may benefit from medical optimization.

PMID- 22639421
TI  - Low-temperature iron-catalyzed depolymerization of polyethers.
AB  - Iron will: The iron-catalyzed depolymerization of a range of polyethers is
      studied. The products of the depolymerization reactions are chloroesters, which
      can be used as starting materials for new polymers. In the presence of simple
      iron salts extraordinary catalyst activities and selectivities are feasible at
      low temperature.

PMID- 22639422
TI  - Chiral stable phenalenyl radical: synthesis, electronic-spin structure, and
      optical properties of [4]helicene-structured diazaphenalenyl.

PMID- 22639423
TI  - In situ photoreduced silver nanoparticles on cysteine: an insight into the origin
      of chirality.
AB  - A delicate system, that is, in situ photoreduced silver metal nanoparticles (NPs)
      formed from a combination of Ag(+) complexes with L- or D-cysteine, enables the
      introduction of chirality. This chirality is essentially programmed by a
      synergetic interplay between the CO(2)(-) and NH(3)(+) groups on cysteine, rather
      than the formation of a chiral metal core (see figure).

PMID- 22639424
TI  - Depressive symptoms in older people with metabolic syndrome: is there a
      relationship with inflammation?
AB  - OBJECTIVE: To investigate if there is a higher prevalence of depressive symptoms
      in older people with metabolic syndrome (MetS) compared with those without and
      whether dedpressive symptoms are independently associated to MetS and its single
      components and to the inflammatory markers. METHODS: Physical parameters,
      standard blood analytes, high sensitivity C-reactive protein (hsCRP) and
      erythrocyte sedimentation rate (ESR) were assessed. Fifteen-item Geriatric
      Depression Scale and mini mental state examination (MMSE) were administered.
      RESULTS: One hundred thirty-three subjects were enrolled. MetS patients (57)
      exhibited higher prevalence of depressive symptoms (p < 0.0001), worse cognitive
      function (p < 0.0001), and higher levels of ESR and hsCRP were higher (p <
      0.0001). The univariate analysis showed a linear strong correlation of depressive
      symptoms (p < 0.0001) with the MMSE score (r = -0.422), body mass index (r =
      0.414), MetS (r = 0.582), number of MetS components (r = 0.663), fasting blood
      glucose (r = 0.565), ESR (r = 0.565), hsCRP (r = 0.745), central obesity (r =
      0.269; p = 0.002), and high-density lipoprotein cholesterol (r = -0.241; p =
      0.005). However, the multivariate analysis showed that only age (B = -0.093; p =
      0.032), MetS (B = 1.446; p = 0.025), fasting blood glucose (B = 0.039; p =
      0.005), and hsCRP (B = 7.649; p < 0.0001) were independently associated with
      depressive symptoms. CONCLUSIONS: MetS and inflammation are independently
      associated with depressive symptoms in older people. Inflammation may explain
      cognitive decline too. Further investigations are needed to better understand the
      direction of these associations and to determine whether these can be reversible.

PMID- 22639425
TI  - Olefination of carbonyl compounds through reductive coupling of alkenylboronic
      acids and tosylhydrazones.

PMID- 22639426
TI  - One-year outcomes of consecutive patients treated by Endeavor zotarolimus and
      Resolute zotarolimus stents: the impact of polymer coating in drug-eluting stent
      technology.
AB  - BACKGROUND: Polymer-coating represents a key component of drug-eluting stent
      (DES) technology and its possible impact on vessel-wall healing is a matter of
      debate. The clinical impact of different polymer-coating may be assessed by
      comparing the outcome of patients treated by DES having the same stent platform
      and drug, and differing in the polymer. Thus, we compared the clinical outcome of
      patients treated by Endeavor Zotarolimus-eluting stent (E-ZES) and Resolute
      Zotarolimus-eluting stent (R-ZES) as they differ in the polymer-coating only.
      METHODS: At our Institution, E-ZES was available during a first period and then
      it was substituted by the R-ZES during a second period. Clinical, angiographic,
      and procedural data were prospectively collected. Clinical follow-up was
      prospectively obtained up to 1-year. Primary endpoint was the occurrence of major
      adverse cardiac events (MACE) at 12-month. RESULTS: A total of 467 patients
      undergoing percutaneous coronary intervention were enrolled: 233 patients treated
      with E-ZES and 234 with R-ZES. Patients treated by R-ZES had similar clinical
      characteristics and worse angiographic characteristics compared with those
      treated by E-ZES. At 12-month follow-up, MACE rate was significantly lower in the
      R-ZES group compared with E-ZES group (4.2% vs. 14.6%; P < 0.01). This difference
      was due to nonsignificantly lower rates of death and myocardial infarction and to
      significant lower rate of target-lesion-revascularization (R-ZES 3.4% vs. E-ZES
      10.3%, P < 0.01). CONCLUSIONS: The results of this study suggest that the
      clinical outcome of patients treated by DES differing for the polymer coating
      only may be different. Polymer coating is a pivotal, probably underrated,
      component of DES technology which may influence the clinical performance of DES.

PMID- 22639427
TI  - Seasonal variation and response to osmotic challenge in urea transporter
      expression in the dehydration- and freeze-tolerant wood frog, Rana sylvatica.
AB  - Urea accumulation is a universal response to osmotic challenge in anuran
      amphibians, and facilitative urea transporters (UTs) seem to play an important
      role in this process by acting in the osmoregulatory organs to mediate urea
      retention. Although UTs have been implicated in urea reabsorption in anurans,
      little is known about the physiological regulation of UT protein abundance. We
      examined seasonal variation in and effects of osmotic challenge on UT protein and
      mRNA levels in kidney and urinary bladder of the wood frog (Rana sylvatica), a
      terrestrial species that tolerates both dehydration and tissue freezing. Using
      immunoblotting techniques to measure relative UT abundance, we found that UT
      numbers varied seasonally, with a low abundance prevailing in the fall and
      winter, and higher levels occurring in the spring. Experimental dehydration of
      frogs increased UT protein abundance in the urinary bladder, whereas experimental
      urea loading decreased the abundance of UTs in kidney and bladder. Experimental
      freezing, whether or not followed by thawing, had no effect on UT numbers. UT
      mRNA levels, assessed using quantitative real-time polymerase chain reaction, did
      not change seasonally nor in response to any of our experimental treatments.
      These findings suggest that regulation of UTs depends on the nature and severity
      of the osmotic stress and apparently occurs posttranscriptionally in response to
      multiple physiological factors. Additionally, UTs seem to be regulated to meet
      the physiological need to accumulate urea, with UT numbers increasing to
      facilitate urea reabsorption and decreasing to prevent retention of excess urea.

PMID- 22639428
TI  - Chylous ascites after liver transplantation: incidence and risk factors.
AB  - In this study, we evaluated the diagnosis, epidemiology, risk factors, and
      treatment of chylous ascites developing after liver transplantation (LT). Between
      2002 and 2011, LT was performed 693 times in 631 patients at our clinic. One
      hundred fifteen of these patients were excluded for reasons such as
      retransplantation, early postoperative mortality, and insufficient data. Chylous
      ascites developed after LT (mean +/- SD = 8.0 +/- 3.2 days, range = 5-17 days) in
      24 of the 516 patients included in this study. Using univariate and multivariate
      analyses, we examined whether the following were risk factors for developing
      chylous ascites: age, sex, body mass index, graft-to-recipient weight ratio,
      Model for End-Stage Liver Disease score, vena cava cross-clamping time, total
      operation time, Child-Pugh classification, sodium level, portal vein thrombosis
      or ascites before transplantation, donor type, albumin level, and perihepatic
      dissection technique [LigaSure vessel sealing system (LVSS) versus conventional
      suture ligation]. According to a univariate analysis, a low albumin level (P =
      0.04), the presence of ascites before transplantation (P = 0.03), and the use of
      LVSS for perihepatic dissection (P < 0.01) were risk factors for developing
      chylous ascites. According to a multivariate Cox proportional hazards model, the
      presence of pretransplant ascites [P = 0.04, hazard ratio (HR) = 2.8, 95%
      confidence interval (CI) = 1.1-13.5] and the use of LVSS for perihepatic
      dissection (P = 0.01, HR = 5.4, 95% CI = 1.5-34.4) were independent risk factors.
      In conclusion, the presence of preoperative ascites and the use of LVSS for
      perihepatic dissection are independent risk factors for the formation of chylous
      ascites. To our knowledge, this study is the most extensive examination of the
      development of chylous ascites. Nevertheless, our results should be supported by
      new prospective trials.

PMID- 22639429
TI  - Copper-catalyzed enantioselective allylic substitution with readily accessible
      carbonyl- and acetal-containing vinylboron reagents.

PMID- 22639433
TI  - "Click" on tubes: a versatile approach towards multimodal functionalization of
      SWCNTs.
AB  - Organic functionalization of carbon nanotube sidewalls is a tool of primary
      importance in material science and nanotechnology, equally from a fundamental and
      an applicative point of view. Here, an efficient and versatile approach for the
      organic/organometallic functionalization of single-walled carbon nanotubes
      (SWCNTs) capable of imparting multimodality to these fundamental nanostructures,
      is described. Our strategy takes advantage of well-established Cu-mediated
      acetylene-azide coupling (CuAAC) reactions applied to phenylazido-functionalized
      SWCNTs for their convenient homo-/heterodecoration with a number of
      organic/organometallic frameworks, or mixtures thereof, bearing terminal
      acetylene pendant arms. Phenylazido-decorated SWCNTs were prepared by
      chemoselective arylation of the CNT sidewalls with diazonium salts under mild
      conditions, and subsequently used for the copper-mediated cycloaddition protocol
      in the presence of terminal acetylenes. The latter reaction was performed in one
      step by using either single acetylene derivatives or equimolar mixtures of
      terminal alkynes bearing either similar functional groups (masked with
      orthogonally cleavable protecting groups) or easily distinguishable
      functionalities (on the basis of complementary analytical/spectroscopic
      techniques). All materials and intermediates were characterized with respect to
      their most relevant aspects/properties by TEM microscopy, thermogravimetric
      analysis coupled with MS analysis of volatiles (TG-MS), elemental analysis,
      cyclic voltammetry (CV), Raman and UV/Vis spectroscopy. The functional loading
      and related chemical grafting of both primary amino- and ferrocene-decorated
      SWCNTs were spectroscopically (UV/Vis, Kaiser test) and electrochemically (CV)
      determined, respectively.

PMID- 22639434
TI  - Acute and long-term results of carotid stenting under proximal embolic protection
      using the Gore Flow Reversal System.
AB  - OBJECTIVE: This study evaluates short- and long-term results of CAS with the Gore
      Flow Reversal System (GFRS). BACKGROUND: Embolic protection devices are of
      fundamental importance in carotid artery stenting (CAS). Proximal protection has
      potential advantages compared with distal protection. Limited data are available
      regarding the safety of the proximal GFRS. METHODS: CAS was performed with the
      GFRS. Patients' neurological status was assessed during the intervention and at
      follow-up. Results of patients treated before 2006 were also compared to those of
      patients treated after 2006 because of changes in device design. RESULTS: CAS was
      performed in 86 patients with 87 stenoses (symptomatic in 37%). The procedure was
      technically successful in all cases. In 11 patients a transient periprocedural
      neurologic deficit occurred related to temporary cerebral flow compromise during
      balloon occlusion with complete resolution at completion of the procedure. The
      stroke/death rate at one month was 2.3% with a combined ipsilateral stroke and
      death rate at one year of 4.6%. There was no significant difference in event
      rates between the newer and older device version. Overall follow-up time was 484
      +/- 3.4 patient years with a range of 0 to 119 months. The average yearly
      ipsilateral stroke rate including the first 30 days was 0.96%. CONCLUSION: Our
      results demonstrate that CAS using the GFRS is safe whether the original or new
      device versions were used. The periprocedural stroke rate is at least as low as
      the stroke rate reported using distal protection. The long-term stroke rate after
      CAS is low.

PMID- 22639435
TI  - Comparison of entorhinal cortex atrophy between early-onset and late-onset
      Alzheimer's disease using the VSRAD, a specific and sensitive voxel-based
      morphometry.
AB  - BACKGROUND: The most characteristic symptom of Alzheimer's disease (AD) is
      episodic memory impairment, which is closely associated with atrophy of the
      entorhinal cortex. Meanwhile, atypical symptoms are more frequent in early-onset
      AD than in late-onset AD, suggesting that the former subtype has less atrophy in
      the entorhinal cortex. Therefore, we investigated whether the degree of atrophy
      in the entorhinal cortex is different between the two subtypes of AD using the
      voxel-based specific regional analysis system for AD (VSRAD) targeting this
      region. METHODS: The subjects consisted of 198 patients with AD. They were
      divided into two groups, that is, the early-onset AD group with the onset under
      age 65 years (n = 18) and the late-onset AD group with the onset at age 65 years
      or over (n = 180). The degree of atrophy in the entorhinal cortex was quantified
      by application of the VSRAD to magnetic resonance imaging data, and a Z-score >2
      was defined as significant atrophy according to previous studies. RESULTS: The
      early-onset group had significantly lower Z-scores than the late-onset group
      (mean +/- SD: 1.83 +/- 0.92 vs 2.90 +/- 1.40, p < 0.01). The analysis of
      covariance with possible confounding factors as covariates also showed that Z
      scores were significantly lower in the early-onset group than in the late-onset
      group (p < 0.01). The proportion of patients with atrophy was significantly lower
      in the early-onset group than in the late-onset group (44% vs 71%, p < 0.05).
      CONCLUSIONS: The present study using the VSRAD suggests that early-onset AD shows
      less atrophy in the entorhinal cortex than late-onset AD.

PMID- 22639437
TI  - Inhalation studies for the safety assessment of nanomaterials: status quo and the
      way forward.
AB  - While technical and medical potential offered by nanotechnologies increase, the
      safety assessment of engineered nanomaterials (NMs) needs to follow this pace.
      Inhalation is a major route of occupational and environmental exposure, and is
      most relevant for most of the respective safety assessment studies. Control and
      generation of aerosol from the test materials for this route of administration
      are technically demanding, and not surprisingly, there are relatively few NMs
      tested in toxicokinetic, short-term, and subchronic inhalation studies. These
      studies were in part adapted to the peculiarities of inhaled NMs, but few were
      also conducted according to organization for economic co-operation and
      development (OECD) test guidelines. Inhalation studies on the potential to
      develop chronic diseases, or studies to check the potential analogy to
      cardiovascular diseases associated with adverse health effects from ambient air
      pollution, are largely missing. On the way forward, appropriate inhalation
      studies need to be performed on a number of NMs to assess their hazards and to
      provide a sound database for correlation and validation of alternative in vitro
      methods. Moreover, these studies can potentially aid in the grouping of different
      NMs based on their biokinetics or biological effects. For carcinogenic and
      cardiovascular effects, research studies are needed to verify-or disprove-the
      relevance and the mechanisms by which NMs contribute to these effects.

PMID- 22639438
TI  - Aptamer-based origami paper analytical device for electrochemical detection of
      adenosine.
AB  - Paper biosensors: an origami sensor is printed on a single piece of paper, folded
      into a three-dimensional fluidic device, and encapsulated by thermal lamination.
      Aptamer is trapped in the fluidic channel, where it binds to the target and
      releases an enzyme to generate a signal. The device is read out using a digital
      multimeter.

PMID- 22639439
TI  - In memoriam: Eric Engel, M.D., an innovator, mentor, and humanist.

PMID- 22639440
TI  - Metal-metal bond formation between [n]metallocenophanes: synthesis and
      characterisation of a dicarba[2]ruthenocenophanium dimer.
AB  - Feeling the strain: The first example of metal-metal bonding between strained
      [n]metallocenophanes is reported. A dicarba[2]ruthenocenophanium dimer has been
      synthesised through the oxidation of a dicarba[2]ruthenocenophane (see figure).
      The structural and electrochemical characterisation of the dimer is also
      discussed.

PMID- 22639441
TI  - A strategy for atrial septal defect closure in small children that eliminates
      long-term wall erosion risk.
AB  - OBJECTIVES: To evaluate feasibility, efficacy, and safety of an approach to
      atrial septal defect (ASD) occlusion in children <=20 kg that eliminates cardiac
      wall erosion risk. BACKGROUND: Cardiac wall erosion is a potentially catastrophic
      complication of ASD device closure. The HELEX Septal Occluder (HSO) is a
      compliant device with no reports of erosion. The HSO is technically difficult to
      deploy in smaller children and cannot be used to close larger defects. To
      eliminate wall erosion risk, we use the HSO when feasible and surgery for larger
      defects. METHODS: Retrospective review of ASD procedures performed in children
      <=20 kg. RESULTS: Between January 2006 and January 2011, 60 children underwent
      ASD closure. HSO placement was successful in 32 of 34 patients, and surgical
      closure was successful in all of 28 patients. Surgical patients were younger
      (35.1 +/- 12.6 vs. 47.4 +/- 15.3 months, P < 0.01) and smaller (15.3 +/- 3.2 vs.
      12.6 +/- 4.3 kg; P < 0.01) with larger ASDs (15.8 +/- 4.5 vs. 9.8 +/- 3.0 mm; P <
      0.01). No surgical patients demonstrated residual leak. Residual leak was seen in
      14 of 32 (44%) HSO patients on postprocedure day #1 and in 1 of 26 (3.8%) with
      >=6 months follow-up. Indications for surgery included: deficient
      inferior/superior rims (n = 17), provider preference (n = 2), and HSO device not
      feasible (n = 9). Serious adverse events included device embolization with
      percutaneous retrieval (n = 1) and postpericardiotomy syndrome without
      intervention (n = 1). CONCLUSIONS: The HSO can be safely used in most children
      <=20 kg. Our approach to ASD closure is associated with minimal morbidity and
      good short-term results. This approach requires no more than a 15% increase in
      surgical referrals and eliminates risk of cardiac wall erosion.

PMID- 22639442
TI  - Hard templating of nanocrystalline titanium dioxide with chiral nematic ordering.
AB  - Anatase TiO(2) nanocrystals have been organized into high-surface-area (150-230
      m(2) g(-1)) mesoporous films with long-range chiral nematic ordering. The chiral
      structure of the anatase films causes them to selectively reflect circularly
      polarized light and appear iridescent. These materials show replication of
      structural features found in the silica template on nanometer to millimeter
      length scales.

PMID- 22639445
TI  - Supernumerary marker chromosomes derived from chromosome 6: cytogenetic,
      molecular cytogenetic, and array CGH characterization.
AB  - Supernumerary marker chromosomes (SMC) are relatively common in prenatal
      diagnosis. As the clinical outcomes vary greatly, a better understanding of the
      karyotype-phenotype correlation for different SMCs will be important for genetic
      counseling. We present two cases of prenatally detected de novo, small SMCs. The
      markers were present in 80% of amniocyte colonies in Case 1 and 38% of the
      colonies in Case 2. The SMCs were determined to be derived from chromosome 6
      during postnatal confirmation studies. Although the sizes and the chromosomal
      origin of the SMCs in these two cases appeared to be similar, the clinical
      outcomes varied. The clinical manifestations observed in Case 1 included small
      for gestational age, feeding difficulty at birth, hydronephrosis, deviated septum
      and dysmorphic features, while the phenotype is apparently normal in Case 2.
      Array comparative genomic hybridization (CGH) was performed and showed increase
      in dosage for approximately 26 Mb of genetic material from the proximal short and
      long arms of chromosome 6 in Case 1. Results of array CGH were uninformative in
      Case 2, either due to mosaicism or lack of detectable euchromatin. The difference
      in the clinical presentation in these two patients may have resulted from the
      difference in the actual gene contents of the marker chromosomes and/or the
      differential distribution of the mosaicism.

PMID- 22639446
TI  - Percutaneous left ventricular support in cardiogenic shock and severe aortic
      regurgitation.
AB  - Severe aortic regurgitation (AR) is a well-established contraindication to intra
      aortic balloon counterpulsation therapy. We report two cases of medically
      refractory cardiogenic shock in patients with severe AR who were successfully
      bridged to surgical left ventricular assist device implantation by percutaneous
      left atrial to femoral artery mechanical bypass. Further investigation into the
      clinical utility of percutaneous mechanical support in the setting of AR and
      shock is required.

PMID- 22639447
TI  - [P9]+ [Al(OR(F))4)]-, the salt of a homopolyatomic phosphorus cation.
AB  - Positive at last: The first condensed-phase homopolyatomic phosphorus cation
      [P(9)](+) was prepared using a combination of the oxidant [NO](+) and weakly
      coordinating anion, [Al{OC(CF(3))(3)}(4)](-). [P(9)](+) consists of two P(5)
      cages linked by a phosphonium atom to give a D(2d)-symmetric Zintl cluster. NMR
      (see picture), Raman, and IR spectroscopy, mass spectrometry, and quantum
      chemical calculations confirmed the structure.

PMID- 22639443
TI  - Microengineered synthetic cellular microenvironment for stem cells.
AB  - Stem cells possess the ability of self-renewal and differentiation into specific
      cell types. Therefore, stem cells have great potentials in fundamental biology
      studies and clinical applications. The most urgent desire for stem cell research
      is to generate appropriate artificial stem cell culture system, which can mimic
      the dynamic complexity and precise regulation of the in vivo biochemical and
      biomechanical signals, to regulate and direct stem cell behaviors. Precise
      control and regulation of the biochemical and biomechanical stimuli to stem cells
      have been successfully achieved using emerging micro/nanoengineering techniques.
      This review provides insights into how these micro/nanoengineering approaches,
      particularly microcontact printing and elastomeric micropost array, are applied
      to create dynamic and complex environment for stem cells culture.

PMID- 22639448
TI  - Investigation into the suitability of capillary tubes for microcrystalline
      testing.
AB  - A comparison between microcrystalline tests performed on microscope slides and
      flat capillary tubes with inner diameters ranging from 0.1 to 0.7 mm was carried
      out to explore the appropriateness of tubes for rapid testing of suspected drugs
      of abuse in the laboratory as well as in the field. Tests for mephedrone,
      cocaine, and phencyclidine were chosen as examples to investigate the handling of
      the capillary tubes, the influence on crystal habit, size, and the effects on the
      limit of detection. Image stacking software was used to increase the depth of
      field of micrographs taken from developed microcrystals greatly enhancing the
      interpretability even months after carrying out the microcrystalline test.
      Additionally, the potential of seeding capillary tubes with a reagent was
      studied. Pre-treatment of tubes would allow microcrystalline tests to be carried
      out quicker and anywhere without the necessity of taking along expensive and
      hazardous reagents. The sealing of capillary tubes containing developed
      microcrystalline tests in order to preserve results for a long period of time was
      successfully done by applying paraffin wax to the open ends. Finally, it was
      concluded that capillary tubes are suitable vessels for performing
      microcrystalline tests. The increased portability of the improved set-up allows
      tests to be safely executed outside laboratories without impairing the quality of
      the result. Findings were applied to six legal high samples purchased online
      between May and August 2011. The active ingredients like MDAI as well as cutting
      agents like caffeine were successfully identified using the microcrystalline test
      technique in capillary tubes.

PMID- 22639450
TI  - Germline mosacism in Shprintzen-Goldberg syndrome.
AB  - We report on maternal half-sibs born to unaffected, non-consanguineous parents
      with classical Shprintzen-Goldberg syndrome (SGS) who had in addition intestinal
      malrotation and an aberrant subclavian artery. In one other SGS family germline
      mosaicism has been described. SGS is molecularly heterogeneous and has been
      linked to mutations in three genomic loci. This suggests there may be multiple
      other genetic factors that result in a common clinical phenotype and a number of
      investigators have implicated a fourth region (15q25-qter) in the etiology of
      SGS.

PMID- 22639449
TI  - Cellular uptakes, biostabilities and anti-miR-210 activities of chiral arginine
      PNAs in leukaemic K562 cells.
AB  - A series of 18-mer peptide nucleic acids (PNAs) targeted against micro-RNA miR
      210 was synthesised and tested in a cellular system. Unmodified PNAs, R(8) 
      conjugated PNAs and modified PNAs containing eight arginine residues on the
      backbone, either as C2-modified (R) or C5-modified (S) monomers, all with the
      same sequence, were compared. Two different models were used for the modified
      PNAs: one with alternated chiral and achiral monomers and one with a stretch of
      chiral monomers at the N terminus. The melting temperatures of these derivatives
      were found to be extremely high and 5 M urea was used to assess differences
      between the different structures. FACS analysis and qRT-PCR on K562 chronic
      myelogenous leukaemic cells indicated that arginine-conjugated and backbone
      modified PNAs display good cellular uptake, with best performances for the C2
      modified series. Resistance to enzymatic degradation was found to be higher for
      the backbone-modified PNAs, thus enhancing the advantage of using these
      derivatives rather than conjugated PNAs in the cells in serum, and this effect is
      magnified in the presence of peptidases such as trypsin. Inhibition of miR-210
      activity led to changes in the erythroid differentiation pathway, which were more
      evident in mithramycin-treated cells. Interestingly, the anti-miR activities
      differed with use of different PNAs, thus suggesting a role of the substituents
      not only in the cellular uptake, but also in the mechanism of miR recognition and
      inactivation. This is the first report relating to the use of backbone-modified
      PNAs as anti-miR agents. The results clearly indicate that backbone-modified PNAs
      are good candidates for the development of very efficient drugs based on anti-miR
      activity, due to their enhanced bioavailabilities, and that overall anti-miR
      performance is a combination of cellular uptake and RNA binding.

PMID- 22639451
TI  - Deployment of self-expandable stents for complex proximal superficial femoral
      artery lesions involving the femoral bifurcation with or without jailed deep
      femoral artery.
AB  - OBJECTIVE: To (1) compare the outcome of self-expandable stents with versus
      without jailed deep femoral artery (DFA) for proximal superficial femoral artery
      (SFA) lesions, and to (2) ascertain the fate of jailed DFA. BACKGROUND: Complex
      SFA lesions involving the femoral bifurcation (FB) was mostly treated surgically,
      and the role played by endovascular procedures is uncertain. METHODS: We
      retrospectively identified 104 consecutive, de novo lesions involving the SFA
      ostium, stented between April 2005 and September 2010. Depending on the proximal
      stent edge location, the sample was divided between 60 distal common femoral
      artery (CFA) stenting with jailed DFA and 44 ostial SFA stenting without jailed
      DFA. The FB was the segment beginning in the distal CFA, 10 mm proximal to the
      DFA ostium and ending in the SFA and 10 mm distal to the carina. Stented CFA
      lesions proximal to the FB were excluded. The bifurcation was classified as
      patent when free of restenosis and repeat revascularization. RESULTS: The overall
      12-month bifurcation and primary patency rates were 72.5% and 52.0%,
      respectively. Predictors of loss of bifurcation patency were ostial SFA stenting
      and a small stent in the FB. Bifurcation patency (83.3% vs. 56.3%; P < 0.01) and
      primary patency of the SFA (56.2% vs. 37.5%; P = 0.088) were higher after distal
      CFA than after ostial SFA stenting. In 95.7% of distal CFA and 100% of ostial SFA
      stenting, DFA remained patent at 12-month follow-up (P = 0.237). CONCLUSIONS: The
      12-month fate of jailed DFA after distal CFA stenting was acceptable, and the
      bifurcation patency rate was higher than after ostial SFA stenting.

PMID- 22639452
TI  - Synergy effect on morphology switching: real-time observation of photo
      orientation of microphase separation in a block copolymer.

PMID- 22639453
TI  - DNA interaction of the CcrM DNA methyltransferase: a mutational and modeling
      study.
AB  - Caulobacter crescentus CcrM is a DNA-(adenine N6)-methyltransferase that
      methylates adenine in the sequence GANTC with high specificity. To investigate
      its mechanism of DNA recognition, we used the crystal structure of a related
      methyltransferase (M1.MboII, which modifies GAAGA) as a starting point, and
      docked into it a DNA substrate to identify the protein regions that approach the
      DNA. After alignment of CcrM and M1.MboII, we identified four candidate regions
      in CcrM to contain residues involved in DNA recognition. We mutated 20 amino acid
      residues within these regions, purified the CcrM variants, and determined their
      DNA-binding and catalytic activity on a cognate GANTC substrate and on nine near
      cognate substrates, each of which contained a single base-pair substitution in
      the recognition sequence. Altogether, we identified four residues in two of the
      regions, mutations of which resulted in a strong (>100-fold) reduction of
      methylation activity. Our data show that DNA recognition by CcrM is a cooperative
      process, because disruption of critical contacts led to loss of catalytic
      activity but not to a relaxation in specificity. In addition, we identified a
      change in the readout of the fifth base pair in the GANTC sequence with two other
      CcrM variants that showed smaller reductions in overall activity. Based on this
      and the sequence alignment of CcrM with other DNA methyltransferases of same or
      related recognition sequence, we propose roles for these two regions in DNA
      recognition by CcrM.

PMID- 22639454
TI  - Finlay-Marks syndrome: report of two siblings and review of literature.
AB  - Finlay-Marks syndrome (scalp-ear-nipple syndrome), is the infrequently reported
      association of scalp aplasia, malformed ears, and breast abnormalities varying
      from small nipples to complete absence of breasts. Other manifestations are
      variable and some of them resemble ectodermal dysplasia and include dystrophy of
      nails and teeth, sparse hair, decreased sweating, and cutaneous syndactyly of
      digits. Renal anomalies have been reported in some patients leading to
      hypertension and renal insufficiency. Most reported patients have been sporadic
      but familial occurrences following an autosomal dominant pattern of inheritance
      have been reported. We report on two affected siblings, of whom one died in the
      neonatal period due to renal failure. Two affected siblings born to non-affected
      parents may suggest an autosomal recessive inheritance.

PMID- 22639456
TI  - Elements for a rational polymer approach towards carbon nanostructures.

PMID- 22639455
TI  - The transradial approach for carotid artery stenting.
AB  - BACKGROUND: Carotid artery stenting (CAS) is an alternative to carotid
      endarterectomy (CEA) for revascularization of the internal carotid artery (ICA).
      CAS from the femoral approach may be problematic due to peripheral vascular
      disease, anatomical variations of the aortic arch, and access site complications.
      The purpose of this study was to evaluate the right radial approach (RRA) for
      CAS. METHODS: A retrospective analysis of all patients who had undergone
      transradial (TR) CAS at two centers was performed. Demographics, the technique
      used to deploy the sheath in the common carotid, procedural details, results, and
      complications were evaluated. RESULTS: CAS was attempted from TR in 382 patients
      (mean age 68, 70% male). CAS was successful in 347/382 (91%) patients; 201/216
      (93%) right CA, 14/16 (88%) bovine left CA, 132/150 (88%) left CA. The specific
      technique varied with the anatomy. Seven different carotid artery stents (51%
      Xact) and seven different distal embolic protection devices were used. Adverse
      events included two major strokes (0.6%) one of whom died, three minor strokes
      (1%), and no myocardial infarction at 30 days. No bleeding complications occurred
      although 23 (6%) of patients had asymptomatic postprocedure radial occlusion.
      Inadequate catheter support at the origin of the CCA was the technical cause of
      failure in the unsuccessful cases which were then completed from femoral access
      as part of the same procedure. CONCLUSION: The transradial approach is an
      alternative for CAS in the presence of factors that increase the risk or
      difficulty of femoral access.

PMID- 22639457
TI  - Species-specific activity of glycolipid ligands for invariant NKT cells.
AB  - The immunomodulatory glycolipid alpha-galactosylceramide (alpha-GalCer) binds to
      CD1d and exhibits potent activity as a ligand for invariant CD1d-restricted
      natural killer-like T cells (iNKT cells). Structural analogues of alpha-GalCer
      have been synthesised to determine which components are required for CD1d
      presentation and iNKT cell activation, however, to date the importance of the
      phytosphingosine 4-hydroxyl for iNKT cell activation has been disputed. To
      clarify this, we synthesised two 4-deoxy alpha-GalCer analogues (sphinganine and
      sphingosine) and investigated their ability to activate murine and human iNKT
      cells. Analysis revealed that the analogues possessed comparable activity to
      alpha-GalCer in stimulating murine iNKT cells, but were severely compromised in
      their ability to stimulate human iNKT cells. Here we determined that species
      specific glycolipid activity was due to a lack of recognition of the analogues by
      the T-cell receptors on human iNKT cells rather than insufficient presentation of
      the analogues on human CD1d molecules. From these results we suggest that
      glycolipids developed for potent iNKT cell activity in humans should contain a
      phytosphingosine base.

PMID- 22639459
TI  - Balloon-assisted tracking of a guide catheter through difficult radial anatomy: a
      technical report.
AB  - A small caliber or significant tortuosity of radial artery may create difficulty
      in negotiating a 6F or 7F guide catheter while performing intervention through
      transradial approach. We describe a technique that helps tracking a guide
      catheter in such demanding situation for successful completion of procedure
      without increasing the chance of perforation and dissection.

PMID- 22639458
TI  - Contribution of LPP copy number and sequence changes to esophageal atresia,
      tracheoesophageal fistula, and VACTERL association.

PMID- 22639460
TI  - Interstitial 9q34.11-q34.13 deletion in a patient with severe intellectual
      disability, hydrocephalus, and cleft lip/palate.
AB  - Interstitial deletions of chromosome bands 9q34.11-q34.13 are rare. We report on
      a 16-year-old female patient with severe intellectual disability, congenital
      hydrocephalus, cleft lip and palate, talipes equinovarus, epilepsy,
      kyphoscoliosis, convergent strabismus, severe short stature, dystrophy, and
      facial dysmorphic signs. Array analysis revealed a 3.7 Mb interstitial deletion
      in 9q34.11-q34.13. The deletion harbors more than 60 genes, including SPTAN1,
      DYT1/TOR1A, ABL1, ASS1, LAMC3, POMT1, DOLK, and GLE1, mutations in which have
      previously been associated with monogenic disorders. This is the first patient
      with a deletion of this size and position in 9q34.11-q34.13. Reports of
      additional patients with aberrations in this region will be needed to establish
      karyotype-phenotype correlations and to gain information on the contribution of
      individual genes for the clinical manifestations.

PMID- 22639461
TI  - First experience with AndraStent XL implantation in children and adolescents with
      congenital heart diseases.
AB  - OBJECTIVES: To present our experience with a new type of extra-large (dilatable
      up to 25 mm), balloon-expandable, nonpremounted, cobalt-chromium peripheral stent
      with semiopen designed cells: AndraStent. METHODS: Between December 2008 and
      August 2011, 21 AndraStents in 21 patients were implanted into vessel stenoses of
      varied localizations. AndraStents XL of 21, 30, and 39 mm in length were used.
      The median age and weight of patients at stent implantation were 11.6 years
      (range 2.1-19.1 years) and 36 kg (range 11-82 kg), respectively. The stent was
      implanted into the left pulmonary artery stenosis (n = 12), into the aortic
      isthmus (n = 7), into a stenosed aortopulmonary collateral artery (n = 1) and
      into a stenosed systemic venous tunnel postSenning operation (n = 1). RESULTS:
      All the implantations were successfully performed; there was one major vessel
      access complication necessitating vascular surgery. The diameter of the vessel
      stenosis increased significantly (P < 0.05) from a median of 5.7-11 mm. The stent
      foreshortening was only mild. CONCLUSIONS: Our initial results show that
      AndraStents are implantable and efficacious in different vascular stenoses and
      present a valuable alternative to the available large stents. With the
      application of a modified front-loading technique, they can also be implanted in
      smaller children.

PMID- 22639462
TI  - Definition of a critical genetic interval related to kidney abnormalities in the
      Potocki-Lupski syndrome.
AB  - Potocki-Lupski syndrome is a genomic disorder caused by duplication of 17p11.2.
      It is characterized by failure to thrive, intellectual disability, hypotonia, and
      behavioral difficulties. Structural renal anomalies have been observed in <10% of
      affected individuals. We present detailed clinical and molecular data on six
      patients with Potocki-Lupski syndrome, two of whom had renal abnormalities, and
      investigate the prevalence of kidney abnormalities in the mouse model for the
      syndrome. In contrast to affected humans, the mouse model does not demonstrate a
      renal phenotype. Comparison of the duplicated segment in patients with Potocki
      Lupski syndrome and the renal phenotype and the syntenic duplicated region in the
      mouse model allowed us to suggest a 0.285 Mb critical region, including the FLCN
      gene that may be important for development of renal abnormalities in patients
      with this duplication.

PMID- 22639463
TI  - A successful retrograde re-entry at aorta using the Outback LTD catheter for a
      bilateral common iliac artery occlusion.
AB  - The Outback LTD re-entry catheter system has become a valuable tool for
      peripheral intervention and it has been widely used for variable peripheral
      chronic total occlusion (CTO). However, its use in the setting of the aorta was
      restricted because of concerns of bleeding risks resulting from re-entry puncture
      or ballooning. This report presents a case of successful re-entry using the
      Outback LTD Re-Entry Catheter (Cordis, Bridgewater, New Jersy) at the aorta in a
      patient with bilateral common iliac artery occlusion.

PMID- 22639464
TI  - Molecular cytogenetic characterization and genotype/phenotype analysis in a
      patient with a de novo 8p23.2p23.3 deletion/12p13.31p13.33 duplication.
AB  - Genomic copy number imbalances are being increasingly identified as an important
      cause of intellectual disability (ID) and behavioral disturbances. This article
      reports the clinical features, and long term follow-up of a patient with
      neurodevelopmental, cognitive, and behavioral abnormalities associated with
      facial dysmorphism, CNS anomalies, and epilepsy. The karyotype was normal; array
      CGH testing revealed a de novo cryptic aberration with a terminal 8p23.2p23.3
      deletion, and a concomitant 12p13.31p13.33 duplication, of 6.86 Mb, and 8.49 Mb,
      respectively. Our patient clinical features are compared to those of partial 8
      monosomy and/or partial 12p trisomy cases reported in literature, in order to
      establish genotype-phenotype correlations. For some features, for example,
      electroencephalogram (EEG) abnormalities and epilepsy, both abnormalities seem to
      make a contribution, while most phenotypic traits have been assigned to 8p
      monosomy or to 12p trisomy, contributing to a tentative phenotype map for partial
      monosomy of the short arm of chromosome 8, and trisomy of the short arm of
      chromosome 12.

PMID- 22639465
TI  - Changes in the colour of light cue circadian activity.
AB  - The discovery of melanopsin, the non-visual opsin present in intrinsically
      photosensitive retinal ganglion cells (ipRGCs), has created great excitement in
      the field of circadian biology. Now, researchers have emphasized melanopsin as
      the main photopigment governing circadian activity in vertebrates. Circadian
      biologists have tested this idea under standard laboratory, 12h Light: 12h Dark,
      lighting conditions that lack the dramatic daily colour changes of natural
      skylight. Here we used a stimulus paradigm in which the colour of the
      illumination changed throughout the day, thus mimicking natural skylight, but
      luminance, sensed intrinsically by melanopsin containing ganglion cells, was kept
      constant. We show in two species of cichlid, Aequidens pulcher and Labeotropheus
      fuelleborni, that changes in light colour, not intensity, are the primary
      determinants of natural circadian activity. Moreover, opponent-cone photoreceptor
      inputs to ipRGCs mediate the sensation of wavelength change, and not the
      intrinsic photopigment, melanopsin. These results have implications for
      understanding the evolutionary biology of non-visual photosensory pathways and
      answer long-standing questions about the nature and distribution of photopigments
      in organisms, including providing a solution to the mystery of why nocturnal
      animals routinely have mutations that interrupt the function of their short
      wavelength sensitive photopigment gene.

PMID- 22639466
TI  - Influence of water on the work function of certain metals.
AB  - Experiments were carried out to explore the effect of light on Au, Pt and Cu
      surfaces immersed in water, in order to study the changes of work function
      arising from the interaction between the metallic surfaces and water. The results
      show an action of liquid water about three times larger than that of low
      temperature ice. Theoretical calculations, present in literature, have predicted
      values much lower than those we measured. The substantial changes in work
      function measured here appear to arise from the complex structure of water in the
      vicinity of the metal surface.

PMID- 22639467
TI  - Does Religion Increase the Prevalence and Incidence of Obesity in Adulthood?
AB  - Previous research reveals that religion in America is related to variations in
      body weight. This article examines the relationships between religion and both
      body mass index (BMI) and obesity, which have increased in prevalence in the
      United States over the past two decades. Using longitudinal data from a national
      sample of adults, this study prospectively examines whether dimensions of
      religious life are associated with weight gain and the development of obesity
      during eight years of follow-up. We examine four dimensions of religiosity
      (attendance, salience, media practice, and consolation) and religious
      affiliation. Ordinary least squares regression analyses reveal that high levels
      of religious media practice are associated with higher BMI in women. Logistic
      regression analyses reveal that high levels of religious media practice and
      affiliation with a Baptist denomination increased the risk of obesity for women,
      but that a high level of religious consolation reduced the risk of obesity
      incidence for men. Attendance at religious services was associated with a lower
      risk of the incidence of obesity for women, suggesting the importance of studying
      links between dimensions of religious life and body weight.

PMID- 22639468
TI  - Failure to Consider Future Consequences Increases the Effects of Alcohol on
      Aggression.
AB  - The failure to consider the future consequences of one's behavior is a major risk
      factor for aggression. Aggressive people tend to act first, and think later. Some
      people focus on the -here and now rather than on the future, a tendency measured
      by the Consideration of Future Consequences (CFC) scale (Strathman, Gleicher,
      Boninger, & Edwards, 1994). Alcohol intoxication is a neuro-biological variable
      that produces similar effects. Participants in the present experiment completed
      the CFC scale and then consumed either an alcohol or a placebo beverage. Next,
      they competed against a same-sex ostensible partner on an interpersonally
      adversarial competitive task in which the winner could administer electric shocks
      to the loser (the aggression measure). As expected, aggression was highest in
      intoxicated persons with low CFC scores. Being unconcerned about the future
      consequences of one's actions, in conjunction with acute alcohol intoxication,
      combine in a pernicious manner to increase aggression.

PMID- 22639469
TI  - Shape change along geodesics with application to cleft lip surgery.
AB  - Continuous shape change is represented as curves in the shape space. A method for
      checking the closeness of these curves to a geodesic is presented. Three large
      databases of short human motions are considered and shown to be well approximated
      by geodesics. The motions are thus approximated by two shapes on the geodesic and
      the rate of progress along the path. An analysis of facial motion data taken from
      a study of subjects with cleft lip or cleft palate is presented that allows the
      motion to be considered independently from the static shape. Inferential methods
      for assessing the change in motion are presented. The construction of predicted
      animated motions is discussed.

PMID- 22639470
TI  - Metropolitan Heterogeneity and Minority Neighborhood Attainment: Spatial
      Assimilation or Place Stratification?
AB  - Using geo-referenced data from the Panel Study of Income Dynamics, in conjunction
      with decennial census data, this research examines metropolitan-area variation in
      the ability of residentially mobile blacks, Hispanics, and whites to convert
      their income into two types of neighborhood outcomes-neighborhood racial
      composition and neighborhood socioeconomic status. For destination tract racial
      composition, we find strong and near-universal support for the "weak version" of
      place stratification theory; relative to whites, the effect of individual income
      on the percent of the destination tract population that is non-Hispanic white is
      stronger for blacks and Hispanics, but even the highest earning minority group
      members move to tracts that are "less white" than the tracts that the highest
      earning whites move to. In contrast, for moves into neighborhoods characterized
      by higher levels of average family income, we find substantial heterogeneity
      across metropolitan areas in minorities' capacity to convert income into
      neighborhood quality. A slight majority of metropolitan areas evince support for
      the "strong version" of place stratification theory, in which blacks and
      Hispanics are less able than whites to convert income into neighborhood
      socioeconomic status. However, a nontrivial number of metropolitan areas also
      evince support for spatial assimilation theory, where the highest-earning
      minorities achieve neighborhood parity with the highest-earning whites. Several
      metropolitan-area characteristics, including residential segregation, racial and
      ethnic composition, immigrant population size, poverty rates, and municipal
      fragmentation, emerge as significant predictors of minority-white differences in
      neighborhood attainment.

PMID- 22639471
TI  - WHY DO IMMIGRANT YOUTH WHO NEVER ENROLL IN U.S. SCHOOLS MATTER? AN EXAMINATION OF
      SCHOOL ENROLLMENT AMONG MEXICANS AND NON-HISPANIC WHITES.
AB  - Using data from the 2000 Public Use Sample of the U.S. Census, this research
      examines how estimates of school enrollment and school-work patterns among
      Mexican-origin adolescents are affected by including or excluding young
      immigrants who never enrolled in U.S. schools. The analysis demonstrates that a
      non-trivial share of adolescents who were born in Mexico almost certainly never
      enrolled in U.S. schools; these youth most likely migrated to the United States
      for work. Excluding these adolescents from analyses substantially reduces gaps in
      school enrollment between Mexicans and Whites and between native and foreign-born
      Mexicans. Excluding never-enrolled immigrant youth also changes the relationship
      between duration of U.S. residence and idleness among Mexican immigrant youth,
      revealing that additional years of residence in the United States increase the
      likelihood of being out of school and not working compared to in school and not
      working. Overall, inferences about the level of school enrollment and intra
      ethnic differences in school enrollment by duration of residence depend on how
      those who are likely to have never enrolled in U.S. schools are treated.
      Inferences about interethnic differences also are affected, although they are
      somewhat less sensitive to this issue.

PMID- 22639472
TI  - Public Perception of Environmental Issues in a Developing Setting: Environmental
      Concern in Coastal Ghana.
AB  - OBJECTIVE: Balancing environmental quality with economic growth in less developed
      settings is clearly a challenge. Still surprisingly little empirical evidence has
      been brought to bear on the relative priority given environmental and
      socioeconomic issues among the residents themselves of such settings. This
      research explores such perceptions.  METHODS: We undertake survey research with
      2500 residents of coastal Ghana on policy issues, focusing on environmental
      topics.  RESULTS: Our analyses reveal a significant amount of environmental
      awareness, with education and political engagement consistently predicting higher
      levels of concern. In addition, environmental issues are deemed important even
      when considered relative to other socioeconomic issues.  CONCLUSION: In the end,
      we argue that our work sheds light on global environmentalism and the ways in
      which local populations in less developed settings prioritize social and
      environmental concerns. This work also has important policy implications since
      insight on local perceptions may help buttress policy responses designed to cope
      with global change.

PMID- 22639473
TI  - Multigram Synthesis of a Chiral Substituted Indoline Via Copper-Catalyzed Alkene
      Aminooxygenation.
AB  - (S)-5-Fluoro-2-(2,2,6,6-tetramethylpiperidin-1-yloxymethyl)-1-tosylindoline, a 2
      methyleneoxy-substituted chiral indoline, was synthesized on multigram scale
      using an efficient copper-catalyzed enantioselective intramolecular alkene
      aminooxygenation. The synthesis is accomplished in four steps and the indoline is
      obtained in 89% ee (>98% after one recrystallization). Other highlights include
      efficient gram-scale synthesis of the (4R,5S)-di-Ph-box ligand and efficient
      separation of a monoallylaniline from its bis(allyl)aniline by-product by
      distillation under reduced pressure.

PMID- 22639474
TI  - Acid-Facilitated Debenzylation of N-Boc, N-Benzyl Double Protected 2
      Aminopyridinomethylpyrrolidine Derivatives.
AB  - 2-Aminopyridinomethyl pyrrolidines represent a class of highly potent and
      selective neuronal nitric oxide synthase inhibitors. Conditions for a Mitsunobu
      reaction of a naphthol and a hindered secondary alcohol were optimized to give
      good to excellent yields. A key step in the synthesis of these inhibitors is the
      deprotection of the benzyl group from the N-Boc and N-Bn double protected 2
      aminopyridine ring at a late stage of the synthesis, which has been proven
      difficult in our previous syntheses. Acetic acid was found to facilitate the N-Bn
      deprotection.

PMID- 22639475
TI  - Adult Attachment and Motivated Attention to Social Images: Attachment-Based
      Differences in Event-Related Brain Potentials to Emotional Images.
AB  - Differences in adult attachment may concord with differences in social
      perception. The present study aimed to measure neural activity associated with
      the presentation of visual social stimuli. In an affective oddball paradigm,
      event-related brain potentials were recorded while participants viewed negative,
      positive, and neutral images of people and categorized them according to valence.
      Brain response amplitudes were examined across valence categories and across
      attachment groups. Results revealed differences between anxious and avoidant
      groups in "emotion bias." The avoidant group displayed a bias towards more neural
      activation in response to negative compared to positive images. The anxious group
      trended in the opposite direction. Results are discussed in terms of possible
      attachment-based differences in motivated attention to social stimuli.

PMID- 22639477
TI  - Profile effects in early bilingual language and literacy.
AB  - Bilingual children's language and literacy is stronger in some domains than
      others. Reanalysis of data from a broad-scale study of monolingual English and
      bilingual Spanish-English learners in Miami provided a clear demonstration of
      "profile effects," where bilingual children perform at varying levels compared to
      monolinguals across different test types. The profile effects were strong and
      consistent across conditions of socioeconomic status, language in the home, and
      school setting (two way or English immersion). The profile effects indicated
      comparable performance of bilingual and monolingual children in basic reading
      tasks, but lower vocabulary scores for the bilinguals in both languages. Other
      test types showed intermediate scores in bilinguals, again with substantial
      consistency across groups. These profiles are interpreted as primarily due to the
      "distributed characteristic" of bilingual lexical knowledge, the tendency for
      bilingual individuals to know some words in one language but not the other and
      vice versa.

PMID- 22639476
TI  - A single strain-based growth law predicts concentric and eccentric cardiac growth
      during pressure and volume overload.
AB  - Adult cardiac muscle adapts to mechanical changes in the environment by growth
      and remodeling (G&R) via a variety of mechanisms. Hypertrophy develops when the
      heart is subjected to chronic mechanical overload. In ventricular pressure
      overload (e.g. due to aortic stenosis) the heart typically reacts by concentric
      hypertrophic growth, characterized by wall thickening due to myocyte radial
      growth when sarcomeres are added in parallel. In ventricular volume overload, an
      increase in filling pressure (e.g. due to mitral regurgitation) leads to
      eccentric hypertrophy as myocytes grow axially by adding sarcomeres in series
      leading to ventricular cavity enlargement that is typically accompanied by some
      wall thickening. The specific biomechanical stimuli that stimulate different
      modes of ventricular hypertrophy are still poorly understood. In a recent study,
      based on in-vitro studies in micropatterned myocyte cell cultures subjected to
      stretch, we proposed that cardiac myocytes grow longer to maintain a preferred
      sarcomere length in response to increased fiber strain and grow thicker to
      maintain interfilament lattice spacing in response to increased cross-fiber
      strain. Here, we test whether this growth law is able to predict concentric and
      eccentric hypertrophy in response to aortic stenosis and mitral valve
      regurgitation, respectively, in a computational model of the adult canine heart
      coupled to a closed loop model of circulatory hemodynamics. A non-linear finite
      element model of the beating canine ventricles coupled to the circulation was
      used. After inducing valve alterations, the ventricles were allowed to adapt in
      shape in response to mechanical stimuli over time. The proposed growth law was
      able to reproduce major acute and chronic physiological responses (structural and
      functional) when integrated with comprehensive models of the pressure-overloaded
      and volume-overloaded canine heart, coupled to a closed-loop circulation. We
      conclude that strain-based biomechanical stimuli can drive cardiac growth,
      including wall thickening during pressure overload.

PMID- 22639478
TI  - Cutpoint selection for discretizing a continuous covariate for generalized
      estimating equations.
AB  - We consider the problem of dichotomizing a continuous covariate when performing a
      regression analysis based on a generalized estimation approach. The problem
      involves estimation of the cutpoint for the covariate and testing the hypothesis
      that the binary covariate constructed from the continuous covariate has a
      significant impact on the outcome. Due to the multiple testing used to find the
      optimal cutpoint, we need to make an adjustment to the usual significance test to
      preserve the type-I error rates. We illustrate the techniques on one data set of
      patients given unrelated hematopoietic stem cell transplantation. Here the
      question is whether the CD34 cell dose given to patient affects the outcome of
      the transplant and what is the smallest cell dose which is needed for good
      outcomes.

PMID- 22639479
TI  - Frailty Modeling via the Empirical Bayes Hastings Sampler.
AB  - Studies of ocular disease and analyses of time to disease onset are complicated
      by the correlation expected between the two eyes from a single patient. We
      overcome these statistical modeling challenges through a nonparametric Bayesian
      frailty model. While this model suggests itself as a natural one for such complex
      data structures, model fitting routines become overwhelmingly complicated and
      computationally intensive given the nonparametric form assumed for the frailty
      distribution and baseline hazard function. We consider empirical Bayesian methods
      to alleviate these difficulties through a routine that iterates between
      frequentist, data-driven estimation of the cumulative baseline hazard and Markov
      chain Monte Carlo estimation of the frailty and regression coefficients. We show
      both in theory and through simulation that this approach yields consistent
      estimators of the parameters of interest. We then apply the method to the short
      wave automated perimetry (SWAP) data set to study risk factors of glaucomatous
      visual field deficits.

PMID- 22639480
TI  - Conceptualizing and Measuring Working Memory and its Relationship to Aphasia.
AB  - BACKGROUND: General agreement exists in the literature that individuals with
      aphasia can exhibit a working memory deficit that contributes to their language
      processing impairments. Though conceptualized within different working memory
      frameworks, researchers have suggested that individuals with aphasia have limited
      working memory capacity, impaired attention-control processes as well as impaired
      inhibitory mechanisms. However, across studies investigating working memory
      ability in individuals with aphasia, different measures have been used to
      quantify their working memory ability and identify the relationship between
      working memory and language performance.  AIMS: The primary objectives of this
      article are to (1) review current working memory theoretical frameworks, (2)
      review tasks used to measure working memory, and (3) discuss findings from
      studies that have investigated working memory as they relate to language
      processing in aphasia.  MAIN CONTRIBUTION: Though findings have been consistent
      across studies investigating working memory ability in individuals with aphasia,
      discussion of how working memory is conceptualized and defined is often missing,
      as is discussion of results within a theoretical framework. This is critical, as
      working memory is conceptualized differently across the different theoretical
      frameworks. They differ in explaining what limits capacity and the source of
      individual differences as well as how information is encoded, maintained, and
      retrieved. When test methods are considered within a theoretical framework,
      specific hypotheses can be tested and stronger conclusions that are less
      susceptible to different interpretations can be made.  CONCLUSIONS: Working
      memory ability has been investigated in numerous studies with individuals with
      aphasia. To better understand the underlying cognitive constructs that contribute
      to the language deficits exhibited by individuals with aphasia, future
      investigations should operationally define the cognitive constructs of interest
      and discuss findings within theoretical frameworks.

PMID- 22639482
TI  - Towards A Discretely Actuated Steerable Cannula for Diagnostic and Therapeutic
      Procedures.
AB  - We have designed, developed, and evaluated the performance of a multi-degree-of
      freedom discretely actuated steerable cannula with shape memory alloy
      (SMA)actuators. This will enable us to deliver diagnostic as well as therapeutic
      devices to the target location through the hollow inner core of the cannula. We
      propose to use SMAs to generate bending forces due to its small size and high
      power density. We annealed the SMA wires through a customized training process in
      arc shape and mounted them at discrete locations on the outer surface of the
      cannula to enable joint motion. A pulse width modulation(PWM)-based control
      scheme was implemented to control all SMA actuators simultaneously to enable
      multiple joint motion using a single power supply. The proposed controller was
      validated through an experiment inside gelatin to mimic the motion of the cannula
      inside a medium which requires a significant amount of force to move the joints
      of the cannula. Trajectory planning using a suitable metric and trajectory
      execution were successfully implemented. To demonstrate the delivery of a
      diagnostic tool through our cannula, we demonstrate that we can pass an optical
      coherence tomography probe through the cannula and perform in situ micro-scale
      imaging.

PMID- 22639481
TI  - Anticancer Activity of Self-Assembled Molecular Rectangles via Arene-Ruthenium
      Acceptors and a New Unsymmetrical Amide Ligand.
AB  - Two new and large molecular rectangles 4 and 5 were synthesized from two
      different arene-ruthenium [Ru(2)(MU-eta(4)-C(2)O(4))(MeOH)(2)(eta(6)-p
      Pr(i)C(6)H(4)Me)(2)][O(3)SCF(3)](2) (2), and [Ru(2) (p-cymene)(2) (donq)
      (OH(2))(2)] [O(3)SCF(3)](2) (donq = 5,8-dioxydo-1,4-naphthaquinonato) (3)
      acceptors and a new unsymmetrical N-(4-(pyridin-4-ylethynyl)phenyl)
      isonicotinamide (1) donor ligand. X-ray crystallography of 4 confirmed a
      molecular rectangle. The (1)H NMR spectra of both rectangles 4 and 5 showed a
      mixture of two structural, head-to-tail (HTL) and head-to-head (HTH) type,
      isomers in a 1:1 ratio. The cytotoxicities of both rectangles have been
      established against Colo320 (colorectal cancer), A549 (lung cancer), MCF-7(breast
      cancer) and H1299 (lung cancer) human cancer cell lines. The cytotoxicity of
      rectangle 5 was found to be considerably stronger against all cancer cell lines
      than that of the reference drug cisplatin.

PMID- 22639483
TI  - Understanding and Changing Older Adults' Perceptions and Learning of Social
      Media.
AB  - An exploratory study was conducted to answer the following questions: What are
      older adults' perceptions of social media? What educational strategies can
      facilitate their learning of social media? A thematic map was developed to
      illustrate changing perceptions from the initial unanimous, strong negative to
      the more positive but cautious and to the eventual willingness to actually
      contribute content. Privacy was the primary concern and key perceptual barrier to
      adoption. Effective educational strategies were developed to overcome privacy
      concerns, including: 1) introducing the concepts before introducing the
      functions; 2) responding to privacy concerns; and 3) making social media
      personally relevant.

PMID- 22639484
TI  - Compare diagnostic tests using transformation-invariant smoothed ROC curves().
AB  - Receiver operating characteristic (ROC) curve, plotting true positive rates
      against false positive rates as threshold varies, is an important tool for
      evaluating biomarkers in diagnostic medicine studies. By definition, ROC curve is
      monotone increasing from 0 to 1 and is invariant to any monotone transformation
      of test results. And it is often a curve with certain level of smoothness when
      test results from the diseased and non-diseased subjects follow continuous
      distributions. Most existing ROC curve estimation methods do not guarantee all of
      these properties. One of the exceptions is Du and Tang (2009) which applies
      certain monotone spline regression procedure to empirical ROC estimates. However,
      their method does not consider the inherent correlations between empirical ROC
      estimates. This makes the derivation of the asymptotic properties very difficult.
      In this paper we propose a penalized weighted least square estimation method,
      which incorporates the covariance between empirical ROC estimates as a weight
      matrix. The resulting estimator satisfies all the aforementioned properties, and
      we show that it is also consistent. Then a resampling approach is used to extend
      our method for comparisons of two or more diagnostic tests. Our simulations show
      a significantly improved performance over the existing method, especially for
      steep ROC curves. We then apply the proposed method to a cancer diagnostic study
      that compares several newly developed diagnostic biomarkers to a traditional one.

PMID- 22639485
TI  - A random-sum Wilcoxon statistic and its application to analysis of ROC and LROC
      data.
AB  - The Wilcoxon-Mann-Whitney statistic is commonly used for a distribution-free
      comparison of two groups. One requirement for its use is that the sample sizes of
      the two groups are fixed. This is violated in some of the applications such as
      medical imaging studies and diagnostic marker studies; in the former, the
      violation occurs since the number of correctly localized abnormal images is
      random, while in the latter the violation is due to some subjects not having
      observable measurements. For this reason, we propose here a random-sum Wilcoxon
      statistic for comparing two groups in the presence of ties, and derive its
      variance as well as its asymptotic distribution for large sample sizes. The
      proposed statistic includes the regular Wilcoxon rank-sum statistic. Finally, we
      apply the proposed statistic for summarizing location response operating
      characteristic data from a liver computed tomography study, and also for
      summarizing diagnostic accuracy of biomarker data.

PMID- 22639486
TI  - Scaling of Prosocial Behavior in Cities.
AB  - Previous research has examined how various behaviors scale in cities in relation
      to their population size. Behavior related to innovation and productivity has
      been found to increase per capita as the size of the city increases, a phenomenon
      known as superlinear scaling. Criminal behavior has also been found to scaling
      superlinearly. Here we examine a variety of prosocial behaviors (e.g., voting and
      organ donation), which also would be presumed to be categorized into a single
      class of scaling with population. We find that, unlike productivity and
      innovation, prosocial behaviors do not scale in a unified manner. We argue how
      this might be due to the nature of interactions that are distinct for different
      prosocial behaviors.

PMID- 22639487
TI  - Parenting Practices of Anxious and Non-Anxious Mothers: A Multi-method Multi
      informant Approach.
AB  - Anxious and non-anxious mothers were compared on theoretically derived parenting
      and family environment variables (i.e., over-control, warmth, criticism, anxious
      modeling) using multiple informants and methods. Mother-child dyads completed
      questionnaires about parenting and were observed during an interactional task.
      Findings revealed that, after controlling for race and child anxiety, maternal
      anxiety was associated with less warmth and more anxious modeling based on
      maternal-report. However, maternal anxiety was not related to any parenting
      domain based on child-report or independent observer (IO) ratings. Findings are
      discussed in the context of the impact of maternal anxiety on parenting and
      suggest that child, rather than maternal, anxiety may have a greater influence on
      parental behavior.

PMID- 22639488
TI  - Improving older adults' e-health literacy through computer training using NIH
      online resources.

PMID- 22639489
TI  - Detection of Cytochrome P450 mRNA in Tissue Sections and Cell Lines Using Enzyme
      Labeled Fluorescence In Situ Hybridization.
AB  - Cytochrome P450s (P450s) constitute a superfamily of enzymes that metabolize a
      broad array of xenobiotics. The ability to measure basal and induced levels of
      P450 mRNA in specific cells and tissues should provide valuable insight regarding
      the functional role and heterogeneous expression of these enzymes in chemically
      related diseases. Methodologies for detecting cell-specific mRNA expression
      patterns typically rely on radiolabeled probes and photographic emulsions, often
      coupled with long exposure times. These studies were conducted to evaluate an
      enzyme-labeled fluorescence (ELF) in situ hybridization technique to detect
      specific P450 mRNA. Deparaffinized, formalin-fixed tissue sections and cells from
      culture were incubated for 12 hours with 5'-biotinylated 20-base DNA oligomer
      probes (20-mer). Specific hybridization was detected using a streptavidin
      alkaline-phosphatase conjugate followed by incubation with the ELF substrate,
      yielding a bright, yellow-green fluorescent signal. In this study, utility of the
      technique was demonstrated using cultured rat hepatorna cells, and tissue
      sections from rat liver and human oral epithelium. Ribonuclease A pretreatment of
      the sample, omission of the probe, competition with a nonbiotinylated oligomer,
      and the use of only partially homologous probes served as negative controls to
      demonstrate the specificity of the hybridization signal. Our results clearly
      demonstrated the ability of ELF in situ hybridization to discriminately detect
      cell-specific P450 mRNA in tissue sections and cultured cells. This technique
      eliminates the use of radioactivity and enables in situ detection of mRNAs with
      relative ease, efficiency, specificity, and high sensitivity.

PMID- 22639491
TI  - Traversing Material Scales: Macroscale LBL-Assembled Nanocomposites with
      Microscale Inverted Colloidal Crystal Architecture.
AB  - The introduction of three-dimensional (3D) architecture to functional materials
      allows for the addition of unique characteristics such as special deformation
      patterns, negative Poison's ratio, negative thermal expansion, controlled
      biological interactions, and mass transport properties. It also aids in bridging
      the dimensional gap between layer-by-layer (LBL) assembled nanocomposites and
      macroscale applications while retaining the advantages of their nanoscale
      organization. Fabrication of 3D microscale features by traditional techniques are
      often restricted to a limited variety of materials and do not include hybrid
      organic-inorganic nanocomposites. This work describes a new method to synthesize
      macroscale materials with hierarchically controlled architecture by using LBL
      deposition in the voids of hexagonally packed arrays of uniform microspheres and
      can be potentially extended to a large variety of materials. Establishing
      systematic techniques to produce materials with hierarchical architecture
      involving nano-, micro-, and potentially millimeter scale features with fairly
      independent control at all levels, allows for the investigation of structural
      influences on material properties and for the development of new practical
      applications due to the unusual combinations of properties that can be achieved.

PMID- 22639490
TI  - Mathematical Modeling of Viral Zoonoses in Wildlife.
AB  - Zoonoses are a worldwide public health concern, accounting for approximately 75%
      of human infectious diseases. In addition, zoonoses adversely affect agricultural
      production and wildlife. We review some mathematical models developed for the
      study of viral zoonoses in wildlife and identify areas where further modeling
      efforts are needed.

PMID- 22639492
TI  - Load-bearing increase in alumina evoked by introduction of a functional glass
      gradient.
AB  - Alumina is the most commonly used ceramic in orthopedics due mainly to its wear
      resistance and chemical inertness. However, alumina has relatively low load
      bearing capacity compared to other advanced ceramics, such as zirconia. We
      hypothesized that grading the elastic modulus at the surfaces may substantially
      increase the load-bearing capacity of alumina. In this study, graded structures
      were fabricated by infiltrating glass into dense alumina plates, resulting in a
      diminished modulus at the surface layers. The plates were then bonded to
      polycarbonate substrates and subjected to flexural loading with various loading
      rates spanning five orders of magnitude (dynamic fatigue) in water. Infiltrated
      specimens showed an increase in flexural load over homogenous controls for all
      loading rates, despite the graded alumina exhibiting greater load rate dependence
      than their homogenous counterparts. Our results indicate that controlled elastic
      gradients at the surface could be highly beneficial in improving the load-bearing
      capacity of alumina ceramics.

PMID- 22639493
TI  - Moderate Wine Consumption Inhibits the Development of the Metabolic Syndrome: The
      Study of Women's Health Across the Nation (SWAN).
AB  - We investigated the relationship between wine consumption and the metabolic
      syndrome (MetS) in a longitudinal, eight-year study of the natural history of the
      menopause transition at seven geographical sites in the United States. Although
      similar in age, the 527 African American women had a worse metabolic profile than
      1057 Caucasian women. Moderate wine consumption (one glass/day) was less common
      among African American women but was associated with a better lipid profile in
      both ethnic groups. Compared to women who drank one glass of wine per day, those
      who consumed no wine had twice the risk of developing the MetS.

PMID- 22639495
TI  - Current concept in oral and maxillofacial surgery.

PMID- 22639494
TI  - The relations among theory of mind, behavioral inhibition, and peer interactions
      in early childhood.
AB  - The current study examined relations among child temperament, peer interaction,
      and theory of mind (ToM) development. We hypothesized that 1) children classified
      as behaviorally inhibited at 24 months would show less ToM understanding at 36
      months in comparison to non-behaviorally inhibited children, 2) children who
      displayed negative peer interaction behaviors in a peer dyadic interaction at 24
      months would exhibit less ToM understanding at 36 months, and 3) Behavioral
      inhibition (BI) and the degree of negative behaviors during a peer interaction
      would jointly influence ToM development, such that children with both heightened
      BI and negative peer interaction behaviors would exhibit worse ToM performance
      than behaviorally inhibited children who did not display negative social
      behaviors. Both BI and negative peer interaction behaviors were associated with
      passing fewer ToM tasks. The data revealed that children high in both BI and
      negative peer interaction behaviors passed fewer ToM tasks at 36 months of age
      than those high in BI and low in negative peer interactions or those low in BI.

PMID- 22639496
TI  - Etiological factors of temporomandibular joint disorders.
AB  - The temporomandibular joint receives its name from the two bones that enter into
      its formation, namely the temporal bone and the mandible. This complex synovial
      system is composed of two temporomandibular joints together with their
      articulating ligaments and masticatory muscles. This articulation affects other
      synovial joints that relate specifically to masticatory function. The causes of
      temporomandibular disorders are complex and multifactorial. There are numerous
      factors that can contribute to temporomandibular disorders. In some instances a
      single factor may serve one or all of these roles. Iatrogenic injuries can act as
      both initiating as well as predisposing factors. The term craniomandibular
      disorder is used synonymously with the term temporomandibular disorders and is
      considered a major cause of nondental pain in the orofacial pain region. The
      successful management of temporomandibular disorders is dependent on identifying
      and controlling the contributing factors. The temporomandibular disorders are
      more common in females, the reason is not clearly known. The following article
      provides detailed information regarding temporomandibular joint disorders.

PMID- 22639497
TI  - Biomechanics and orthodontic treatment protocol in maxillofacial distraction
      osteogenesis.
AB  - As in the traditional combined surgical and orthodontic procedures, an
      Orthodontist can plays vital role in treatment planning and the orthodontic
      treatment of patient undergoing distraction osteogenesis. This role includes
      predistraction assessment of the craniofacial skeleton and occlusal function, pre
      distraction, and post-distraction orthodontic care. Based on clinical evaluation,
      dental study models, photographic analysis, cephalometric evaluation, and three
      dimensional computed tomographic analysis, the Orthodontist, in collaboration
      with the Surgeon, plans distraction device placement and the predicted vectors of
      distraction. Finally, as in other forms of orthognathic surgery, the practice of
      distraction osteogenesis depends on the cooperation and planning between
      orthodontist and surgeon as a team. Purpose of this paper is to review
      biomechanics and orthodontic treatment protocol of distraction osteogenesis in
      the maxillofacial region.

PMID- 22639498
TI  - Sports dentistry.
AB  - Sports dentistry is one of the most recent and upcoming field in dentistry. It
      mainly includes the prevention and management of athletics-related orofacial
      injuries and associated oral diseases. The sports or team dentist assists
      athletes in the prevention, treatment, and diagnosis of oral injuries. The most
      significant aspect in preventing sports-related orofacial injuries is wearing
      basic protective devices such as properly-fitting helmets, face masks and/or
      mouth guards. Dental injuries are the most common type of orofacial injury
      sustained during participation in sports. Many athletes are not aware of the
      health implications of a traumatic injury to the mouth or of the potential for
      incurring severe head and orofacial injuries while playing. The dentist can play
      an imperative role in informing athletes, coaches and patients about the
      importance of preventing orofacial injuries in sports. The aim of this paper is
      to increase professional awareness and interest for orientation toward sports
      dentistry.

PMID- 22639499
TI  - Clinical evaluation of cissus quadrangularis and moringa oleifera and osteoseal
      as osteogenic agents in mandibular fracture.
AB  - BACKGROUND: Ayurveda the ancient science of medicine describes various herb
      preparations that achieve the hastening of bone healing. Harjor showed clinical
      efficacy in the treatment of fractures. OBJECTIVES: The comparative evaluation of
      herbal agents as osteogenic agents in mandibular fractures. STUDY DESIGN: The
      patients were divided into four groups. Group 1: Osteoseal; Group 3: Harjor
      (Cissus quadrangularis); Group 2: Moringa (Moringa Oleifera); Group 4: Placebo.
      RESULT AND CONCLUSION: Pain, Swelling, Tenderness, Mobility reduction is maximum
      in Osteoseal group and minimum in Placebo. There was an increase in the serum
      calcium and phosphorus level at different follow-ups in each groups but there was
      a decrease in the placebo group. Ca, Ca+, Phosphrous increase was maximum in the
      group 1.

PMID- 22639500
TI  - Incidence of lingual nerve paraesthesia following mandibular third molar surgery.
AB  - CONTEXT: The surgical removal of impacted mandibular third molar is associated
      with minor but expected complications like pain, swelling, bruising and trismus.
      The lingual nerve damage sometimes occurs after the removal of mandibular third
      molar producing impaired sensation or permanent sensory loss. This complication
      is usually unexpected and unacceptable for the patients particularly if no prior
      warning has been given. AIMS: The aim of the present clinical prospective study
      was to determine the clinical incidence of lingual nerve injury following
      mandibular third molar removal and to analyze possible factors for the lingual
      nerve injury. SETTINGS AND DESIGN: Clinical prospective study in the Department
      of Oral Surgery, Punjab Government Dental College and Hospital, Amritsar.
      MATERIALS AND METHODS: Ninety patients were selected randomly, amongst the
      patients, who reported to our department from January 2009 to December 2009 for
      the surgical removal of impacted mandibular third molar. To minimize the risk of
      lingual nerve injury, the standard terence wards incision was made in all cases
      and only buccal flap was raised. STATISTICAL ANALYSIS: The small number of
      paraesthesia precluded statistical analysis. RESULTS: Out of 90 patients, six
      patients were diagnosed with lingual nerve paraesthesia. The overall incidence
      rate of lingual nerve injury was 6.6%. CONCLUSIONS: It can be concluded that
      lingual nerve paraesthesia can occur with or without reflection of lingual flap
      in spite of all the measures taken to protect it. It may be contributed to the
      fact of anatomical variations of lingual nerve.

PMID- 22639501
TI  - A questionnaire survey on postoperative intermaxillary fixation in mandibular
      trauma: Is its use based on evidence?
AB  - CONTEXT: This questionnaire survey was conducted to ascertain if the practice of
      the routine use of postoperative intermaxillary fixation (IMF) in mandibular
      trauma (of the dentate segments only) was based on evidence available in the
      literature. SETTINGS AND DESIGN: This study was designed as a questionnaire
      survey that would be conducted among surgeons operating on mandibular fractures
      in the state of Gujarat. MATERIALS AND METHODS: A typed questionnaire was sent to
      oral maxillofacial surgeons and plastic surgeons of Gujarat state for their
      feedback by post. Approval of the ethical committee of the university was
      obtained. All the feedback forms received back were included for this survey
      which included 25 oral and maxillofacial surgeons and 25 plastic surgeons.
      RESULTS: Although majority of the surgeons use open reduction and internal
      fixation (ORIF), 25% of the surgeons still prefer using only IMF as the sole
      modality of treatment for the said group of mandibular fractures. According to
      our survey, the majority of surgeons use IMF routinely in the postoperative
      setting even after using ORIF. Occlusion seems to be the critical factor among
      72% of surgeons in deciding on the use of IMF as an adjunct after ORIF. Seventy
      eight percent of surgeons vary their period of IMF based on the site of fracture.
      CONCLUSION: The routine use of postoperative IMF in cases of mandibular fractures
      seems to find favor among surgeons despite lack of sound scientific evidence
      supporting its use. There is also no evidence to suggest that if IMF is not used,
      it would have deleterious effects on occlusion or otherwise.

PMID- 22639502
TI  - Healing of cervical necrotizing fasciitis using amniotic membrane as a dressing
      material.
AB  - AIMS AND OBJECTIVES: Early recognition, aggressive surgical debridement, removal
      of cause, appropriate antibiotic therapy, improvement of immunocompromised state
      and dressing of the wound is the treatment of necrotizing cervical fasciitis.
      There are so many reported cases of burn and some reported cases of necrotizing
      fasciitis where amniotic membrane has been used as a dressing material, and that
      encouraged us to use it as a dressing material in our cases. MATERIALS AND
      METHODS: Six cases of necrotizing cervical fasciitis reported to our department
      in a span of five years (2005 to 2010). Amniotic membrane taken from placenta of
      suitable donors had been used as a dressing material in these cases. Data
      collection included age, sex, medical history of the patients, size of the wound,
      pain felt by the patient, time taken for granulation tissue formation, total
      healing time, size of the scar and need for future reconstruction. RESULTS: The
      sample consisted of six patients with a mean age of 45 years. Four of them were
      male. Etiology was always odontogenic. Five patients were immunocompromised.
      Three patients were chronic alcoholic. Average size of the wound was 42 square
      centimeter. Mean time taken for formation of granulation tissue was 22 days; mean
      total healing time was 36 days. In every case patient reported with pain, which
      gradually diminished after first application of amniotic membrane. In three
      cases, pain on fourth day after first application of amniotic membrane was nil
      (VAS scale). In rest three cases, pain on sixth day after first application of
      amniotic membrane was nil (VAS scale). Average size of the scar was 9 cm(2).
      Secondary scar revision was required in all six cases. CONCLUSION: Our study
      concludes that amniotic membrane can be used effectively as a dressing material
      in necrotizing cervical fasciitis.

PMID- 22639503
TI  - Knowledge, attitude and practice regarding risk of HIV infection through
      accidental needlestick injuries among dental students of Raichur, India.
AB  - BACKGROUND: Injuries from occupational accidents are associ-ated with agents of
      biological risk, as they are the gateway to serious and potentially lethal
      infectious diseases that can be spread by contact between people. Several studies
      have demonstrated that dental students are among the most vulnerable to blood
      borne exposure. OBJECTIVES: To assess the knowledge, attitude and practice
      regarding risk of HIV transmission through accidental needlestick injury amongst
      dental students and providing supportive and proper guidelines regarding
      needlestick injuries and HIV infection. STUDY DESIGN: This was a cross-sectional
      study done at a dental college attached to a tertiary care hospital, which
      included third, fourth year students and interns. The results obtained were
      subjected to statistical analysis using Chi-square test. RESULTS: Of the 120
      students, 13 (11%) were not even aware that virus could be transmitted through
      infected needle. A significant proportion of the third year students i.e. 27
      (67.5%) were not aware of correct method of disposal of disposable needles and
      syringes as against interns 17 (42.5%). Around 31 (26%) said that they would
      promote active bleeding at the site of injury and 37 (30%) said they would take
      post-exposure prophylaxis. CONCLUSION: Dental professionals are at a risk of
      occupational acquisition of HIV primarily due to accidental exposure to infected
      blood and body fluids. There is a need of correcting the existing misconceptions
      through education programs early in the course and providing supportive and
      proper guidelines regarding needlestick injuries and HIV infection.

PMID- 22639504
TI  - Pediatric facial injuries: It's management.
AB  - BACKGROUND: Facial injuries in children always present a challenge in respect of
      their diagnosis and management. Since these children are of a growing age every
      care should be taken so that later the overall growth pattern of the facial
      skeleton in these children is not jeopardized. PURPOSE: To access the most
      feasible method for the management of facial injuries in children without
      hampering the facial growth. MATERIALS AND METHODS: Sixty child patients with
      facial trauma were selected randomly for this study. On the basis of examination
      and investigations a suitable management approach involving rest and observation,
      open or closed reduction and immobilization, trans-osseous (TO) wiring, mini bone
      plate fixation, splinting and replantation, elevation and fixation of zygoma,
      etc. were carried out. RESULTS AND CONCLUSION: In our study fall was the
      predominant cause for most of the facial injuries in children. There was a 1.09%
      incidence of facial injuries in children up to 16 years of age amongst the total
      patients. The age-wise distribution of the fracture amongst groups (I, II and
      III) was found to be 26.67%, 51.67% and 21.67% respectively. Male to female
      patient ratio was 3:1. The majority of the cases of facial injuries were seen in
      Group II patients (6-11 years) i.e. 51.67%. The mandibular fracture was found to
      be the most common fracture (0.60%) followed by dentoalveolar (0.27%), mandibular
      + midface (0.07) and midface (0.02%) fractures. Most of the mandibular fractures
      were found in the parasymphysis region. Simple fracture seems to be commonest in
      the mandible. Most of the mandibular and midface fractures in children were
      amenable to conservative therapies except a few which required surgical
      intervention.

PMID- 22639505
TI  - Maxillary unicystic ameloblastoma: A review of the literature.
AB  - The term unicystic ameloblastoma (UA) refers to those cystic lesions that show
      clinical, radiographic, or gross features of a jaw cyst, but on histologic
      examination show a typical ameloblastomatous epithelium lining part of the cyst
      cavity, with or without luminal and/or mural tumor growth. Although the histology
      suggests that cystic ameloblastomas follow a biologically low-grade course,
      recent evidence suggests that they may often behave clinically as aggressive
      tumors. This is supported by the high incidence of cortical perforation, tooth
      resorption, increase in lesion size, bony destruction, and a high rate of
      recurrence after simple enucleation. Here, the authors present a case report on
      unicystic variant of ameloblastoma in the maxilla. An attempt has been made to
      emphasize that it can involve the maxillary jaw, which is rarely affected and
      could be more aggressive than previously thought. A literature review on the
      topic has been added along with the case report. It is important to remember that
      a proper and timely diagnosis of the character and extent of a UA (with a
      thorough histopathologic examination of the entire specimen) can help in the
      overall long-term well-being of the patient.

PMID- 22639506
TI  - Pleomorphic adenoma of the palate.
AB  - Pleomorphic adenoma (PA) is the most common salivary gland tumor, accounting for
      about 40-70% of all major and minor salivary gland tumors. The commonest sites
      for intraoral PA are palate, buccal mucosa and lips. Palatal PA presents
      clinically as a painless, slow-growing mass found on posterior lateral aspect.
      The aim of this article is to present a case of palatal PA, which was treated
      successfully by surgical excision.

PMID- 22639507
TI  - Overgrowth of costochondral graft in temporomandibular joint ankylosis: An
      unusual case.
AB  - Costochondral graft (CCG) replacement of the mandibular condyle was first
      described by Gilles in 1920. Since then CCGs have gained increasing popularity in
      reconstruction of the TMJ and condyle in children. The influence of CCGs on
      mandibular growth and function is not known in detail. Adaptation of the graft
      has been observed to be better in children, but CCGs have also been shown to grow
      in adult patients. One of the major disadvantages of the CCGs is its growth
      pattern, which is extremely unpredictable and may manifest as excessive growth or
      no growth at all. A mandibular overgrowth on the grafted site can actually be
      more troublesome than lack of growth. Furthermore, maxillary growth is
      proportionality influenced by vertical mandibular growth of the graft. This is a
      report of such a case in which a bizarre overgrowth of the graft was seen
      following a reconstruction of TMJ by CCG and the devastating outcomes of the
      treatment. He required one further resection because the grafted tissue had
      overgrown five years later.

PMID- 22639508
TI  - Oral tuberculosis involving maxillary gingiva.
AB  - Tuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis,
      which is transmitted by aerosolized saliva droplets among individuals in close
      contact with expelled sputum of a diseased patient. However, TB lesions of the
      oral cavity are often overlooked in the differential diagnosis. We report here a
      case of tuberculosis of oral cavity affecting the gingiva of a 24-year-old male.

PMID- 22639509
TI  - Management of parotid fistula using hypertonic saline.
AB  - Parotid fistula is a very rare, unpleasant and painful complication following
      surgery in the maxillofacial region. Although there is consensus in the
      literature that acute parotid injury must be explored primarily and all injured
      structures be repaired accurately, the treatment of the chronic injury is
      controversial. Numerous methods of treatment, conservative as well as aggressive,
      have been described with varying success and morbidity. This paper presents a
      simple but effective and conservative method of treating this complication with
      the use of hot hypertonic saline.

PMID- 22639510
TI  - Zygomatic abscess as a complication of otitis media.
AB  - Zygomatic abscess is a very rare complication (extra cranial) of acute otitis
      media. Unfamiliarity with the underlying cause of a swollen cheek can lead to
      delay of proper treatment with potential harm to the patient. The ideal treatment
      for these cases is modified radical mastoidectomy with drainage of abscess. We
      herein present a rare case report of zygomatic abscess associated with otitis
      media along with its clinical presentation, root of spread and review of its
      medical and surgical management, with emphasis on the methods for accurate
      diagnosis. We report on a 55-years-old man who presented with right ear discharge
      with decreased hearing. High-resolution computed tomography of temporal bone
      showed irregular osteolytic area involving the posterior portion of the right
      zygomatic process and zygomatico temporal junction, mastoid air cell, middle ear
      cavity with erosion of anterior, lateral, and superior wall. There is a evidence
      of peripherally enhancing collection seen around the right zygomatic process and
      it measures 3.9*1.6 cm with ill-defined swelling of the soft tissue of right
      temporal region (masticatory space). Anterior and posterior margin of EAC also
      shows erosion. The patient underwent a modified radical mastoidectomy with
      drainage of zygomatic abscess. There was an automastoidectomy and organized
      granular mass. Zygomatic root abscess is a rare complication of acute otitis
      media. HRCT scans or magnetic resonance imaging of the temporal bone with wider
      windows are necessary. Appropriate intravenous ntibiotics and adequate surgeries,
      as soon as possible, are recommended.

PMID- 22639511
TI  - Ewing's sarcoma of the mandible.
AB  - Ewing's sarcoma is a malignant tumor of bones that primarily affects children and
      young adults. The true origin of this small round cell lesion still remains
      controversial. It was originally described by James Ewing in 1921 as arising from
      undifferentiated osseous mesenchymal cells; however, recent studies suggest that
      Ewing's tumor might be neuroectodermally derived from various degrees of
      differentiation of the primitive neural tissues. This paper reports a rare case
      of ES of the mandible in an 11-year-old girl, which had been previously
      misdiagnosed and treated as a dental abscess. In the clinical examination, a hard
      immobile expansive mass of 2 cm diameter was observed on the left side of the
      mandible. Radiographic examination revealed a diffuse radiolucent lesion with ill
      defined borders and wide vestibular bone plate destruction. Microscopically, the
      tumor was composed by monotonous small round cells that exhibited
      immunoreactivity for CD99, vimentin and desmin. Surgical resection of mandible
      followed by mandibular reconstruction was adopted. The patient was subjected to
      multiagent chemotherapy with Vincristine [VC], Dactinomycin [AC],
      Cyclophosphamide [CP] and Doxorubicin [AD]).

PMID- 22639512
TI  - Odontogenic myxoma of the maxilla: A report of a rare case and review on
      histogenetic and diagnostic concepts.
AB  - Odontogenic myxoma (OM) is a rare and locally invasive benign neoplasm
      (comprising of 3-6% of all odontogenic tumors) found exclusively in the jaws. OM
      commonly occurs in the second and third decades, and the mandible is involved
      more commonly than the maxilla. The lesion often grows without symptoms and
      presents as a painless swelling. The radiographic features are variable, and the
      diagnosis is therefore not easy. This article presents a rare case of OM
      occurring in the maxilla of a 37-year-old female patient with a brief review of
      the pathogenesis, clinical, radiological, histopathological, ultrastructural and
      immunohistochemical characteristics of OM.

PMID- 22639513
TI  - Dentigerous cyst of maxilla in a young child.
AB  - Dentigerous cysts are the most common odontogenic and developmental cysts arising
      in the jaws. In this article, we report a rare case of dentigerous cyst arising
      from an unerupted canine which had invaded a part of the maxilla in a 6-year-old
      child. The clinical features, radiographic presentation, and the treatment
      modality are described.

PMID- 22639514
TI  - Infected cementoblastoma.
AB  - Cementoblastoma is a relatively uncommon, benign odontogenic neoplasm of jaws.
      Mandible is affected more than the maxilla. The lesions are generally diagnosed
      on a routine radiograph. The localized expansion of cortical plates is observed.
      Radiographically, it consists of well-defined radiopacity with a radiolucent
      band. Here is a case report of a female aged 55 years having swelling in the
      right mandibular angle with an extraoral draining sinus. A panoramic radiograph
      shows a dense radiopaque mass along the roots of the third molar surrounded by a
      radiolucent band. Surgical excision was carried out and a histopathological
      examination was carried out which was suggestive of cementoblastoma.

PMID- 22639515
TI  - Unusual case of postextraction bleeding.
AB  - Vascular anomalies often affect the soft tissues though primary intraosseous
      lesions are uncommon. A 29-year-old patient reported to the Oral and
      Maxillofacial Surgery department of SCB Dental College, Cuttack, with the
      complaint of unusual bleeding from his extracted tooth socket. After undergoing
      routine hematological and radiological investigations and an angiogram, a
      diagnosis of arteriovenous malformation of the right posterior maxilla involving
      the posterior superior alveolar artery was established. Subsequently, the patient
      was treated by right external carotid artery ligation followed by partial
      maxillectomy. Follow-up has been satisfactory all through.

PMID- 22639516
TI  - Myoepithelial carcinoma of the nasopharynx: Case report of a rare entity.
AB  - Myoepithelial carcinomas are rare tumors of salivary glands. Most occur in the
      parotid gland buta few other sites of origin have also been described.
      Myoepithelial carcinoma of the nasopharynx has only been reported very few times.
      Because the lesion is so rare in the nasopharynx, there are no specific
      guidelines for its treatment. We present a rare case of myoepithelial carcinoma
      in the nasopharynx and discuss its diagnostic and therapeutic aspects.

PMID- 22639517
TI  - Non-Hodgkins lymphoma of maxilla: A rare entity.
AB  - Non-Hodgkin's lymphomas are a group of neoplasms that originate from the cells of
      the lymphoreticular system. Forty percent of non-Hodgkin's lymphomas arise from
      extra nodal sites. Non-Hodgkin's lymphomas detected primarily in the bone are
      quite rare, but among jaw lesions, they are more frequently present in the
      maxilla than in the mandible. There are no classical characteristic clinical
      features of lymphomas involving the jaw bones. Swelling, ulcer or discomfort may
      be present in the region of the lymphoma, or it may mimic a periapical pathology
      or a benign condition. Extranodal non-Hodgkins lymphoma of the maxilla could
      present as one of the early manifestation of detrimental diseases. Clinically
      these types of lymphoma can mimic an inflammatory endo-periodontal lesion with
      symptoms of pain and local discomfort. The greater the delay in diagnosis
      subsequently worsens the prognosis. A case of maxillary non-Hodgkin's lymphoma
      with an unusual presentation is discussed.

PMID- 22639518
TI  - Squamous cell carcinoma in a maxillary odontogenic keratocyst: A rare entity.
AB  - Odontogenic cysts in the maxilla are common but a malignant change in an
      odontogenic cyst is a comparatively a rare occurrence; however, these entities
      present with clinical and radiographic features similar to benign, expansible,
      central, odontogenic tumor, or cyst of the jaws. A patient reporting with
      squamous cell carcinoma arising from an odontogenic keratocyst of right maxilla
      has been worked up clinically, radiographically, and pathologically. The case was
      surgically managed and followed up. A 54-year-old male patient with a
      compressible, rapidly growing swelling of right maxilla was clinically diagnosed
      to be a case of odontogenic cyst. On radiologic examination it appeared similar
      to a cystic lesion. An incisional biopsy obtained from the cyst wall showed it to
      be odontogenic keratocyst with histologic evidence of malignant transformation.
      The pathogenesis of the tumor, the biologic progression, and prognosis and
      overall clinical and histopathogical features of this rare malignancy is reported
      and discussed.

PMID- 22639520
TI  - Ectopic third molar in the maxillary sinus.
AB  - Ectopic eruption of teeth into a region other than the oral cavity is rare
      although there have been reports of teeth in the nasal septum, mandibular
      condyle, coronoid process, palate, chin and maxillary sinus. Occasionally, a
      tooth may erupt in the maxillary sinus and present with local sinonasal symptoms
      attributed to chronic sinusitis. We present a case of an ectopic maxillary third
      molar tooth that caused chronic purulent sinusitis in relation to the right
      maxillary sinus.

PMID- 22639519
TI  - Pleomorphic adenoma of the upper lip.
AB  - This case report describes a rare and unusual lesion found in a 33-year-old male,
      which was diagnosed as pleomorphic adenoma of the minor salivary glands in the
      upper lip. The tumor was a circumscribed, large firm mass, about 3 cm in
      diameter, almost obstructing the nares and characterized by slow growth. Complete
      excision was performed and the histopathologic analysis showed pleomorphic
      adenoma. The tumor did not recur. A brief review of the relevant literature is
      also presented.

PMID- 22639521
TI  - Calcifying epithelial odontogenic tumor (Pindborg tumor).
AB  - The calcifying epithelial odontogenic tumor (CEOT) is a rare entity and
      represents less than 1% of all odontogenic tumors. Dr. J J Pindborg (1958) first
      described four cases of this unusual lesion; subsequently Shafer et al coined the
      term Pindborg tumor. This lesion is a locally aggressive benign odontogenic
      neoplasm arising from epithelial tissue. It occurs most commonly in 4(th)-5(th)
      6(th) decade of life and bears no gender predilection. A case of CEOT in a 50
      year-old male arising in the left body region is described.

PMID- 22639522
TI  - Oral biofilm and dental implants: A brief.

PMID- 22639523
TI  - Analysis of Parent, Teacher, and Consultant Speech Exchanges and Educational
      Outcomes of Students With Autism During COMPASS Consultation.
AB  - The significant increase in the numbers of students with autism combined with the
      need for better trained teachers (National Research Council, 2001) call for
      research on the effectiveness of alternative methods, such as consultation, that
      have the potential to improve service delivery. Data from 2 randomized controlled
      single-blind trials indicate that an autism-specific consultation planning
      framework known as the collaborative model for promoting competence and success
      (COMPASS) is effective in increasing child Individual Education Programs (IEP)
      outcomes (Ruble, Dal-rymple, & McGrew, 2010; Ruble, McGrew, & Toland, 2011). In
      this study, we describe the verbal interactions, defined as speech acts and
      speech act exchanges that take place during COMPASS consultation, and examine the
      associations between speech exchanges and child outcomes. We applied the
      Psychosocial Processes Coding Scheme (Leaper, 1991) to code speech acts. Speech
      act exchanges were overwhelmingly affiliative, failed to show statistically
      significant relationships with child IEP outcomes and teacher adherence, but did
      correlate positively with IEP quality.

PMID- 22639525
TI  - Incontinence in Individuals with Rett Syndrome: A Comparative Study.
AB  - Frequency and type of incontinence and its association with other variables were
      assessed in females with Rett Syndrome (RS) (n = 63), using an adapted Dutch
      version of the 'Parental Questionnaire: Enuresis/Urinary Incontinence' (Beetz et
      al. 1994). Also, incontinence in RS was compared to a control group consisting of
      females with non-specific (mixed) intellectual disability (n = 26). Urinary
      incontinence (UI) (i.e., daytime incontinence and nocturnal enuresis) and faecal
      incontinence (FI) were found to be common problems among females with RS that
      occur in a high frequency of days/nights. UI and FI were mostly primary in nature
      and occur independent of participants' age and level of adaptive functioning.
      Solid stool, lower urinary tract symptoms and urinary tract infections (UTI's)
      were also common problems in females with RS. No differences in incontinence
      between RS and the control group were found, except for solid stool that was more
      common in RS than in the control group. It is concluded that incontinence is not
      part of the behavioural phenotype of RS, but that there is an increased risk for
      solid stool in females with RS.

PMID- 22639524
TI  - Condom Use Trajectories in Adolescence and the Transition to Adulthood: The Role
      of Mother and Father Support.
AB  - Few studies have investigated how mother and father support differ on predicting
      youths' sexual risk behavior. We therefore examined the influence of parental
      support on condom use trajectories and its correlates in a predominantly African
      American sample [(N=627; 53% female; M = 14.86 years (SD=. 64)] from adolescence
      to young adulthood. We used hierarchical growth curve modeling to examine the
      relationship between condom use, substance use, psychological distress and
      parental support prospectively. We found that consistent condom use decreased
      over time and was associated negatively with psychological distress and substance
      use. Furthermore, both maternal and paternal support were associated with more
      condom use over time. We discuss the implications of our findings for HIV
      prevention programs.

PMID- 22639526
TI  - Mother Positivity and Family Adjustment in Households with Children with a
      Serious Disability.
AB  - Only limited attention has been given to parent coping resources in the positive
      adjustment of families of children with a disability. This study is the first to
      explore maternal positivity as a psychological coping resource related to family
      adjustment in these families. Consistent with broaden-and-build theory and prior
      positivity research, positivity was operationalized through a ratio of positive
      to negative affect scores. We employed longitudinal tracking over a 1 year
      interval. Children's diagnostic categories included developmental conditions or
      impairments, mental health disorders, complex health conditions, physical/motor
      conditions or impairments, sensory impairments, and provisionally diagnosed
      conditions or impairments. We used a computer assisted telephone survey to gather
      psychological, family, and demographic information from 152 mothers in Alberta,
      Canada. Hierarchical regression analysis indicated mothers' level of positivity
      and age, when controlled for family adjustment at Time 1, accounted for 46% of
      the variance in family adjustment at Time 2. That is, older mothers with higher
      positivity scores were found to live in households with higher levels of family
      adjustment after 1 year. These findings provide promising support for broaden-and
      build theory, which posits that positive experienced emotions can offset and
      diminish the negative health and relationship impacts of chronic stress. Study
      findings support the salience of mothers' positivity as a psychological coping
      resource, which is related to enhanced family adjustment in situations of
      childhood disability.

PMID- 22639527
TI  - Improvements in a Mouse Model of Alzheimer's Disease Through SOD2 Overexpression
      are Due to Functional and Not Structural Alterations.
AB  - Oxidative stress and mitochondrial dysfunction have been implicated in the
      pathogenesis of Alzheimer's disease. We and others have shown that over
      expression of the mitochondrial antioxidant superoxide dismutase 2 (SOD-2) can
      improve many of the pathologies in the Tg2576 mouse model of Alzheimer's disease
      that harbors the Swedish mutation in the amyloid precursor protein. However, it
      is not clear if these improvements are due to functional improvements or
      structural/anatomical changes. To answer this question, we used diffusion tensor
      imaging (DTI) to assess the structural integrity of white matter tracts in the
      control mice, Tg2576 mouse and Tg2576 mice over expressing SOD-2. We observed
      minimal differences in diffusion parameters with SOD-2 over expression in this
      model indicating that the improvements we previously reported are due to
      functional changes and not any alterations to the white matter tractography.

PMID- 22639528
TI  - Revision of ilyphagus chamberlin, 1919 (polychaeta, flabelligeridae).
AB  - Ilyphagus Chamberlin, 1919 includes abyssal, fragile benthic species. Most
      species have large cephalic cages but chaetae are brittle and easily lost which
      may explain why the original definition included species with a cephalic cage or
      without it. The type species, Ilyphagus bythincola Chamberlin, 1919, together
      with another species (Ilyphagus pluto Chamberlin, 1919) were described as lacking
      a cephalic cage whereas a third species (Ilyphagus ascendens Chamberlin, 1919)
      was described with one. To clarify this situation, all available type and non
      type materials were studied. Ilyphagus is redefined to include species with
      digitiform bodies, abundant filiform papillae and a thin body wall; their
      neurochaetae are thick, anchylosed aristate spines, and all species have a
      cephalic cage (in the type species the presence of a cage is inferred from the
      remaining chaetal scars). Ilyphagus pluto, which also lacks a a cephalic cage is
      determined here to be a holothurian. The redefined genus contains Ilyphagus
      bythincola (incl. Ilyphagus ascendens), Ilyphagus coronatus Monro, 1939,
      Ilyphagus hirsutus Monro, 1937, and Ilyphagus wyvillei (McIntosh, 1885).

PMID- 22639529
TI  - Two new spider species of the genus Chrysso O. P.-Cambridge, 1882 (Araneae,
      Theridiidae) in Hainan Island, China.
AB  - Two new spider species of the genus Chrysso O. P.-Cambridge, 1882 are reported
      from Hainan Island, China, Chrysso bifurcasp. n. (male, female) and Chrysso
      bicuspidatasp.n. (male, female). Chrysso bimaculata Yoshida, 1998is recorded from
      China for the first time.

PMID- 22639530
TI  - New species of Prosopodesmus Silvestri, 1910 (Diplopoda, Polydesmida,
      Haplodesmidae) from Queensland, Australia.
AB  - Prosopodesmus cratersp. n., Prosopodesmus kirramasp. n. and Prosopodesmus
      monteithisp. n. are described from the Wet Tropics of north Queensland. The
      hothouse species Prosopodesmus panporus Blower & Rundle, 1980 is recorded from
      rainforest on Queensland's Cape York Peninsula, where it is likely to be native.

PMID- 22639531
TI  - Morphological and molecular evidence for cryptic species of springsnails [genus
      Pseudamnicola ( Corrosella) (Mollusca, Caenogastropoda, Hydrobiidae)].
AB  - Several Pseudamnicola (Corrosella) populations of the central and eastern Iberian
      Peninsula have been ascribed to Pseudamnicola (Corrosella) astieri (Dupuy, 1851),
      though recent evidence demonstrates the species could be endemic to the
      departments of Var and Alpes-Maritimes in France. Through the identification of
      cryptic species using a combined morphological and phylogenetic approach, this
      paper provides a detailed morphological description of Pseudamnicola (Corrosella)
      astieri, clarifying its taxonomic boundaries and confirming it as a French
      endemic. In parallel, by comparing Pseudamnicola (Corrosella) populations from
      the provinces of Castellon and Valencia in Eastern Spain, it was observed that
      rather than Pseudamnicola (Corrosella) astieri they represented a new species
      here described as Pseudamnicola (Corrosella) hauffeisp. n. Among other
      characters, the two species show marked differences in shell shape, male and
      female genital systems, radular formula and concentration of the nervous system.
      Pseudamnicola (Corrosella) hauffeisp. n. was also compared morphologically to
      another two Pseudamnicola (Corrosella) species living in nearby areas
      [Pseudamnicola (Corrosella) hinzi Boeters, 1986 and Pseudamnicola (Corrosella)
      navasiana (Fagot, 1907)], molecularly to Pseudamnicola (Corrosella) falkneri
      (Boeters, 1970), the type species of the subgenus, and to the rest of the
      Pseudamnicola (Corrosella) species described so far. Morphological
      differentiation between the species is supported by a genetic divergence of 7.4%
      inferred from a partial sequence (658 bp) of the mitochondrial gene cytochrome c
      oxidase subunit I (COI). On the basis of an average 8% (5.39 to 11.15%)
      divergence estimated for the COI gene in other Pseudamnicola (Corrosella) species
      reported in GenBank, the existence of two specific entities is here proposed,
      which will have impact on conservation policies both in France and in Spain.

PMID- 22639532
TI  - Acanthodasys paurocactus sp. n., a new species of Thaumastodermatidae
      (Gastrotricha, Macrodasyida) with multiple scale types from Capron Shoal,
      Florida.
AB  - A new species of Acanthodasys (Gastrotricha, Macrodasyida, Thaumastodermatidae)
      is described from sublittoral sediments off the Atlantic coast of Florida.
      Acanthodasys paurocactussp. n. is a relatively small species (to 450 um long)
      with a strap-shaped outline, a series of anterior, lateral, and ventrolateral
      adhesive tubes, paired caudal pedicles with posterior adhesive tubes, and a
      morphologically diverse cuticle. The cuticle contains both spined and unspined
      scales. Unspined scales are present in two general shapes: lanceolate and eye
      shaped, with some transitional shapes. All scales have a thickened rim and
      depressed central region; some scales of both shapes bear either one or more
      central bumps, a parallel ridge, or a perpendicular ridge that gives the
      appearance of a cross-shaped pattern under transmitted light. Spined scales are
      somewhat quadrangular in shape and bear uniancres to 15 um long with a cross
      shaped sectional profile. The new species is now one of five described species to
      possess both spined and spineless scales, and only one of two species to possess
      two types of spineless scales (the second species is an incompletely described
      specimen from Norway).

PMID- 22639533
TI  - Phylogenetic reconsideration of Myrmekiaphila systematics with a description of
      the new trapdoor spider species Myrmekiaphila tigris (Araneae, Mygalomorphae,
      Cyrtaucheniidae, Euctenizinae) from Auburn, Alabama.
AB  - The trapdoor spider genus Myrmekiaphila currently comprises 11 nominal species. A
      recent molecular phylogenetic evaluation of the group identified a number of
      problems with respect to how species and species groups were delineated by Bond
      and Platnick in their 2007 taxonomic revision of the genus. We report herein the
      discovery of a new species, Myrmekiaphila tigrissp. n. The phylogenetic position
      of the species is evaluated using a molecular phylogenetic approach based on a
      set of mtDNA markers. Our preferred phylogenetic hypothesis supports the
      recognition of a new species and further highlights the need to more carefully
      investigate species boundaries within the genus. These results further indicate
      that palpal bulb morphology is rapidly evolving and has likely been a
      contributing factor in rendering a number of species paraphyletic with respect to
      the molecular data.

PMID- 22639534
TI  - Australian Assassins, Part II: A review of the new assassin spider genus
      Zephyrarchaea (Araneae, Archaeidae) from southern Australia.
AB  - The Assassin Spiders of the family Archaeidae from southern Australia are
      revised, with a new genus (Zephyrarchaeagen. n.) and nine new species described
      from temperate, mesic habitats in southern Victoria, South Australia and south
      western Western Australia: Zephyrarchaea austinisp. n., Zephyrarchaea
      barrettaesp. n., Zephyrarchaea grayisp. n., Zephyrarchaea janineaesp. n.,
      Zephyrarchaea maraesp. n., Zephyrarchaea markisp. n., Zephyrarchaea melindaesp.
      n., Zephyrarchaea porchisp. n. and Zephyrarchaea vichickmanisp. n. Specimens of
      the type species, Zephyrarchaea mainae (Platnick, 1991), comb. n., are
      redescribed from the Albany region of Western Australia, along with the holotype
      female of Zephyrarchaea robinsi (Harvey, 2002) comb. n. from the Stirling Range
      National Park. The previously described species Archaea hickmani Butler, 1929
      from Victoria is here recognised as a nomen dubium. A key to species and multi
      locus molecular phylogeny complement the species-level taxonomy, with maps,
      habitat photos, natural history information and conservation assessments provided
      for all species.

PMID- 22639535
TI  - Summary statistics for fossil spider species taxonomy.
AB  - Spiders (Araneae) are one of the most species-rich orders on Earth today, and
      also have one of the longest geological records of any terrestrial animal groups,
      as demonstrated by their extensive fossil record. There are currently around 1150
      described fossil spider species, representing 2.6% of all described spiders (i.e.
      extinct and extant). Data for numbers of fossil and living spider taxa described
      annually (and various other metrics for the fossil taxa) were compiled from
      current taxonomic catalogues. Data for extant taxa showed a steady linear
      increase of approximately 500 new species per year over the last decade,
      reflecting a rather constant research activity in this area by a large number of
      scientists, which can be expected to continue. The results for fossil species
      were very different, with peaks of new species descriptions followed by long
      troughs, indicating minimal new published research activity for most years. This
      pattern is indicative of short bursts of research by a limited number of authors.
      Given the frequent discovery of new fossil deposits containing spiders, a wealth
      of new material coming to light from previously worked deposits, and the
      application of new imaging techniques in palaeoarachnology that allow us to
      extract additional data from historical specimens, e.g. X-ray computed
      tomography, it is important not only to ensure a sustained research activity on
      fossil spiders (and other arachnids) through training and enthusing the next
      generation of palaeoarachnologists, but preferably to promote increased research
      and expertise in this field.

PMID- 22639536
TI  - Review of Chinese Oligaphorurini (Collembola, Onychiuridae) with descriptions of
      two new Palaearctic species.
AB  - A checklist of Chinese Oligaphorurini is given. Two new Chinese species,
      Micraphorura changbaiensissp. n. and Oligaphorura pseudomontanasp. n., are
      described from Changbai Mountain Range. Micraphorura changbaiensis sp. n. has the
      same dorsal pseudocelli formula and number of papillae in Ant. III sensory organ
      as Micraphorura uralica, but they can be easily distinguished by number of
      chaetae in Ant. III sensory organ, ventral pseudocelli formula, ventral
      parapseudocelli formula, number of pseudocelli on subcoxa 1 of legs I-III, dorsal
      axial chaeta on Abd. V and number of chaetae on tibiotarsi. Oligaphorura
      pseudomontana sp. n. is very similar to the species Oligaphorura montana having
      an increased number of pseudocelli on body dorsally, well marked base of antenna
      with 1 pseudocellus and 3 pseudocelli outside, subcoxa 1 of legs I-III with 1
      pseudocellus each, dorsally S-chaetae formula as 11/011/22211 from head to Abd.
      V, S-microchaeta present on Th. II-III, claw without inner teeth and with 1+1
      lateral teeth, and unguiculus with basal lamella; but they can be separated
      easily by the number of pseudocelli on Abd. V and VI terga, parapseudocelli on
      the body, number of chaetae on Th. I tergum, and number of chaetae on tibiotarsi.
      A key to Chinese species of Oligaphorurini is provided in the present paper.

PMID- 22639537
TI  - Two new species of Amblypsilopus Bigot with a key to species from Taiwan
      (Diptera, Dolichopodidae).
AB  - The following two new species of the genus Amblypsilopus Bigot from Taiwan are
      described: Amblypsilopus flavellussp. n. and Amblypsilopus ventralissp. n. One
      species, Amblypsilopus crassatus Yang, 1997, is newly reported from Taiwan. A key
      to the species of the genus from Taiwan is given.

PMID- 22639538
TI  - Description of two new species of Cossidae (Lepidoptera) from China.
AB  - Two new Cossidaespecies from China's Zhejiang and Sichuan provinces are
      described. The new species Phragmataecia monikasp. n.and Patoptoformis
      rimsaitesp. n. superficially resemble related congeners but can be distinguished
      by differences in wing pattern, genitalia and distribution. Checklists of the
      genera Phragmataecia and Patoptoformis are presented.

PMID- 22639539
TI  - Description and DNA barcoding of Tipula ( Pterelachisus) recondita sp. n. from
      the Palaearctic region (Diptera, Tipulidae).
AB  - Tipula (Pterelachisus) recondita Pilipenko & Salmela, sp. n. is described. The
      new species is collected from two localities: Finland, Kittila (North boreal
      ecoregion) and Russia, Primorski kray (Zone of temperate broadleaf and mixed
      forests). Although variation in the structure of male hypopygium between the
      Finnish and Russian populations is observed, DNA barcode sequences differ only by
      three nucleotides (0.2 % K2P distance), supporting presence of one widespread
      species. K2P minimum distances between the new species and 17 other species of
      the subgenus range from 5.3 to 15.8 % (mean 8.8 %). The new species is forest
      dwelling, known from an old-growth herb-rich forest (Finland) and Quercus
      mongolica forest (Russia). The new species is perhaps closest to Tipula
      (Pterelachisus) imitator Alexander and in lesser extent to Tipula (Pterelachisus)
      pauli Mannheims; the inner gonostylus of both species are illustrated.

PMID- 22639540
TI  - Biological nomenclature terms for facilitating communication in the naming of
      organisms.
AB  - A set of terms recommended for use in facilitating communication in biological
      nomenclature is presented as a table showing broadly equivalent terms used in the
      traditional Codes of nomenclature. These terms are intended to help those engaged
      in naming across organism groups, and are the result of the work of the
      International Committee on Bionomenclature, whose aim is to promote harmonisation
      and communication amongst those naming life on Earth.

PMID- 22639541
TI  - Relationship of Neonatal Oral Motor Assessment Scale to Feeding Performance of
      Premature Infants.
AB  - OBJECTIVE: Some premature infants require prolonged tube-feeding, beyond term
      equivalent gestational age. Tools that could prospectively identify such infants
      from among otherwise healthy patients are needed. We examined how well the
      Neonatal Oral Motor Assessment Scale (NOMAS) predicts premature infants'
      transition from tube to oral feeding.  DESIGN: Data from a prospective study of
      sucking behavior as a predictor of feeding skills were used to examine the
      relationship of NOMAS and other nominal predictors to pre-defined feeding
      milestones.  SETTING: Neonatal intensive Care Unit  PATIENTS: 51 tube-fed,
      premature infants  METHODS: NOMAS was administered soon (<72 hours) after oral
      feeding was initiated, and weekly thereafter, until infants reached full oral
      feeding. A timed measure of feeding efficiency was also done as oral feeding was
      initiated. A standardized, permissive protocol for feeding advance was used.
      Nonparametric rank sum tests and ANOVA were used to relate NOMAS, feeding
      efficiency, and other baseline variables to feeding milestones.  RESULTS:
      Gestational age at birth, birth weight, and initial feeding efficiency predicted
      shorter transition and earlier acquisition to full oral feeding; NOMAS scores did
      not predict feeding outcomes.  CONCLUSIONS: NOMAS was a poor predictor, while
      feeding efficiency and other baseline traits were better predictors of feeding
      skills in premature infants.

PMID- 22639542
TI  - FRaC: a feature-modeling approach for semi-supervised and unsupervised anomaly
      detection.
AB  - Anomaly detection involves identifying rare data instances (anomalies) that come
      from a different class or distribution than the majority (which are simply called
      "normal" instances). Given a training set of only normal data, the semi
      supervised anomaly detection task is to identify anomalies in the future. Good
      solutions to this task have applications in fraud and intrusion detection. The
      unsupervised anomaly detection task is different: Given unlabeled, mostly-normal
      data, identify the anomalies among them. Many real-world machine learning tasks,
      including many fraud and intrusion detection tasks, are unsupervised because it
      is impractical (or impossible) to verify all of the training data. We recently
      presented FRaC, a new approach for semi-supervised anomaly detection. FRaC is
      based on using normal instances to build an ensemble of feature models, and then
      identifying instances that disagree with those models as anomalous. In this
      paper, we investigate the behavior of FRaC experimentally and explain why FRaC is
      so successful. We also show that FRaC is a superior approach for the unsupervised
      as well as the semi-supervised anomaly detection task, compared to well-known
      state-of-the-art anomaly detection methods, LOF and one-class support vector
      machines, and to an existing feature-modeling approach.

PMID- 22639543
TI  - Physical Properties of Eu(2+)-Containing Cryptates as Contrast Agents for Ultra
      High Field Magnetic Resonance Imaging.
AB  - The kinetic stabilities and relaxivities of a series of Eu(2+)-containing
      cryptates have been investigated. Transmetallation studies that monitored the
      change in the longitudinal relaxation rate of water protons in the presence of
      Ca(2+), Mg(2+), and Zn(2+) demonstrated that cryptate structure influences
      stability, and two of the cryptates studied were inert to transmetallation in the
      presence of these endogenous ions. The efficacy of these cryptates was determined
      at different magnetic field strengths, temperatures, and pH values. Cryptate
      relaxivity was found to be higher at ultra-high field strengths (7 and 9.4 T)
      relative to clinically relevant field strengths (1.4 and 3 T), but the efficiency
      of these cryptates decreased as temperature increased. In addition, variation in
      pH did not yield significant changes in the efficacy of the cryptates. These
      studies establish a foundation of important properties that are necessary to
      develop effective positive contrast agents for magnetic resonance imaging from
      Eu(2+)-containing cryptates.

PMID- 22639544
TI  - HIV/AIDS and time allocation in rural Malawi.
AB  - AIDS-related morbidity and mortality are expected to have a large economic impact
      in rural Malawi, because they reduce the time that adults can spend on production
      for subsistence and on income-generating activities. However, households may
      compensate for production losses by reallocating tasks among household members.
      The data demands for measuring these effects are high, limiting the amount of
      empirical evidence. In this paper, we utilize a unique combination of qualitative
      and quantitative data, including biomarkers for HIV, collected by the 2004 Malawi
      Diffusion and Ideational Change Project, to analyze the association between AIDS
      related morbidity and mortality, and time allocation decisions in rural Malawian
      households. We find that AIDS-related morbidity and mortality have important
      economic effects on women's time, whereas men's time is unresponsive to the same
      shocks. Most notably, AIDS is shown to induce diversification of income sources,
      with women (but not men) reallocating their time, generally from work-intensive
      (typically farming and heavy chores) to cash-generating tasks (such as casual
      labor).

PMID- 22639545
TI  - Keratocystic odontogenic tumors: predictive factors of recurrence by Ki-67 and
      AgNOR labelling.
AB  - PURPOSE: The purpose of the present study was to investigate the possible role of
      Ki-67 and argyrophilic nucleolar organizing regions (AgNOR) between the recurrent
      and nonrecurrent keratocystic odontogenic tumors (KCOTs). Another aim was to
      compare the correlation between these two markers. MATERIALS AND METHODS: 22
      KCOTs were evaluated retrospectively. The actual proliferative activity of the
      KCOT was measured by Ki-67 labelling index and argyrophilic nucleolar organizing
      regions AgNOR count per nucleus. RESULTS: Recurrence occurred in 3 patients
      (13.6%) during the follow-up period (mean follow-up, 37.8 months) The Ki-67 and
      AgNOR counts were significantly higher in the recurrent lesions comparing to the
      non-recurrent lesions. (p=0,045; p=0,049) The correlation between Ki-67 and AgNOR
      counts was found to be positive (r=0,853 p=0,0001). CONCLUSION: Within the limit
      of the present study, it is thought that Ki-67 and AgNOR might be helpful as a
      prognostic marker for the recurrences of KCOTs. These markers reinforced the
      meaning of the new classification of the lesion as an odontogenic tumor.
      Enucleation with curettage or decompression following enucleation with curettage
      is a simple and appropriate surgical model for the treatment of KCOT despite the
      relative high recurrence rate. On the other hand, the conservative treatment can
      be chosen only if there is no coronoid invasion, no interruptive cortical lysis
      and no tissular invasion.

PMID- 22639546
TI  - Cerebral falx mature teratoma with rare imaging in an adult.
AB  - Intracranial mature teratoma is a rare lesion in adults. Despite several
      intracranial mature teratomas had been reported not to be located at the midline
      region, no one was found to be within cerebral falx. Herein, we reported a 37
      year-old female patient with an intracranial mature teratoma confined within
      frontal cerebral falx. Her main complaint was intermitted headache, which could
      not be relieved recently by taking painkiller. Excepting for mild papilledema, we
      did not find positive neurological signs on physical examination. CT scanning
      showed it was a round homogenously hypodense lesion with hyperdense signal at its
      rim. MRI revealed the lesion was 3.5 cm*3.6 cm*4.5 cm in volume, with uniformed
      hypointensity on T1WI, hyperintensity on T2WI and enhancement in the capsule. It
      was totally removed via inter-hemispheric approach, and we found the lesion was
      confined within the frontal cerebral falx. Postoperatively, it was proved
      histologically to be a mature teratoma. At three years of fellow up, neither
      neurological deficits nor recurrent sings on MRI was found. To our best
      knowledge, this is the first case of intracranial mature teratoma within cerebral
      falx.

PMID- 22639547
TI  - Pooled analyses of the associations of polymorphisms in the GRK4 and EMILIN1
      genes with hypertension risk.
AB  - BACKGROUND: The GRK4 and EMILIN1 genes have been suggested to be involved in the
      development of hypertension. However, the results have been inconsistent. In this
      study, a meta-analysis was performed to clarify the associations of polymorphisms
      in the GRK4 and EMILIN1 genes with hypertension risk. METHODS: Published
      literature from PubMed and Embase databases were retrieved. Pooled odds ratios
      (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random
      effects model. RESULTS: Five studies for polymorphisms in the GRK4 gene and five
      studies for polymorphisms in the EMILIN1 gene were identified. The results
      suggested that rs1801058 polymorphism in the GRK4 gene was inversely associated
      with hypertension among East Asians (TT vs. CC: OR=0.39, 95%CI 0.28-0.55) and
      positively associated with hypertension among Europeans (TT vs. CC: OR= 2.38,
      95%CI 1.38-4.10). Rs2960306 polymorphism in the GRK4 gene was significantly
      associated with hypertension among Europeans (TT vs. GG: OR=1.92, 95%CI 1.13
      3.27). The significant associations were also observed for rs2011616 and
      rs2304682 polymorphisms in the EMILIN1 gene among Japanese (rs2011616: AA vs. GG:
      OR=0.38, 95%CI 0.18-0.82; rs2304682: GG vs. CC: OR=0.37, 95%CI 0.17-0.81) but not
      among Chinese. CONCLUSIONS: This meta-analysis suggested that rs1801058
      polymorphism in the GRK4 gene was associated with hypertension in East Asians and
      Europeans. The significant association was also found for rs2960306 polymorphism
      in the GRK4 gene among Europeans. In addition, there were significant
      associations of rs2011616 and rs2304682 polymorphisms in the EMILIN1 gene with
      hypertension among Japanese.

PMID- 22639548
TI  - The Symptom Experience of Patients with Cancer.

PMID- 22639549
TI  - To share or not to share: When do toddlers respond to another's needs?
AB  - The developmental origins of sharing remain little understood. Using procedures
      adapted from research on prosocial behavior in chimpanzees, we presented 18- and
      25-month-old children with a sharing task in which they could choose to deliver
      food to themselves only, or to both themselves and another person, thereby making
      it possible for them to share without personal sacrifice. The potential
      recipient, a friendly adult, was either silent about her needs and wants or made
      them explicit. Both younger and older toddlers chose randomly when the recipient
      was silent. However, when the recipient vocalized her desires 25-month-olds
      shared whereas younger children did not. Thus, we demonstrate that children
      voluntarily share valued resources with others by the end of the second year of
      life, but that this depends on explicit communicative cues about another's need
      or desire.

PMID- 22639550
TI  - Alginate Microsphere Fabrication Using Bipolar Wave-Based Drop-on-Demand Jetting.
AB  - Scale-up microsphere fabrication with controllable microsphere size has always
      been an exciting manufacturing challenge. The objective of this study is to
      experimentally study the effects of material properties and operating conditions
      on the formability of alginate microspheres and the microsphere size during drop
      on-demand (DOD)-based single nozzle jetting. Alginate microspheres have been
      fabricated using bipolar wave-based drop-on-demand jetting, and its formability
      and size have been studied especially as a function of sodium alginate and
      calcium chloride concentrations, voltage rise/fall times, dwell and echo times,
      excitation voltage amplitudes, and frequency. It is found that 1) the formability
      is sensitive to the sodium alginate and calcium chloride concentrations, dwell
      and echo voltages, and voltage dwell time; and the formability decreases with the
      sodium alginate concentration but increases with the calcium chloride
      concentration, dwell and echo voltages, and voltage dwell time; 2) the size is
      not sensitive to the sodium alginate and calcium chloride concentrations but
      increases first with the dwell time and then decreases; and 3) the size increases
      with the dwell and absolute echo voltage amplitudes.

PMID- 22639552
TI  - African American and European American Mothers' Beliefs about Negative Emotions
      and Emotion Socialization Practices.
AB  - OBJECTIVE: Mothers' beliefs about their children's negative emotions and their
      emotion socialization practices were examined.  DESIGN: Sixty-five African
      American and 137 European American mothers of 5-year-old children reported their
      beliefs and typical responses to children's negative emotions, and mothers'
      emotion teaching practices were observed.  RESULTS: African American mothers
      reported that the display of negative emotions was less acceptable than European
      American mothers, and African American mothers of boys perceived the most
      negative social consequences for the display of negative emotions. African
      American mothers reported fewer supportive responses to children's negative
      emotions than European Americans and more nonsupportive responses to children's
      anger. African American mothers of boys also reported more nonsupportive
      responses to submissive negative emotions than African American mothers of girls.
      However, no differences were found by ethnicity or child gender in observed
      teaching about emotions. Group differences in mothers' responses to negative
      emotions were explained, in part, by mothers' beliefs about emotions. 
      CONCLUSIONS: Differences in beliefs and practices may reflect African American
      mothers' efforts to protect their children from discrimination.

PMID- 22639553
TI  - AN AUGMENTED IMMERSED INTERFACE METHOD FOR MOVING STRUCTURES WITH MASS.
AB  - We present an augmented immersed interface method for simulating the dynamics of
      a deformable structure with mass in an incompressible fluid. The fluid is modeled
      by the Navier-Stokes equations in two dimensions. The acceleration of the
      structure due to mass is coupled with the flow velocity and the pressure. The
      surface tension of the structure is assumed to be a constant for simplicity. In
      our method, we treat the unknown acceleration as the only augmented variable so
      that the augmented immersed interface method can be applied. We use a modified
      projection method that can enforce the pressure jump conditions corresponding to
      the unknown acceleration. The acceleration must match the flow acceleration along
      the interface. The proposed augmented method is tested against an exact solution
      with a stationary interface. It shows that the augmented method has a second
      order of convergence in space. The dynamics of a deformable circular structure
      with mass is also investigated. It shows that the fluid-structure system has bi
      stability: a stationary state for a smaller Reynolds number and an oscillatory
      state for a larger Reynolds number. The observation agrees with those in the
      literature.

PMID- 22639551
TI  - Innate Immunity in the Small Intestine of the Preterm Infant.
AB  - The gastrointestinal tract comprises the largest surface area of the human body.
      This area is constantly exposed to myriad antigens as well as the large number of
      bacteria that coexist in the intestinal lumen. To protect against this exposure
      and help distinguish "self " from "foreign," the intestinal tract has evolved a
      sophisticated barrier defense system that includes both innate and adaptive
      immune systems. However, infants who are born preterm do not have the benefit of
      an adequate immune response and, therefore, are more susceptible to bacterial
      injury, inflammation, and intestinal diseases such as necrotizing enterocolitis.
      In this review, we discuss the components of innate immunity that help to protect
      the small intestine as well as current knowledge about the role of these
      components in the pathophysiology of necrotizing enterocolitis.

PMID- 22639554
TI  - Construct Validity and Measurement Invariance of the Peabody Picture Vocabulary
      Test-III Form A in the Performance of Struggling Adult Readers: Rasch Modeling.
AB  - PURPOSE: The aim of this study was to apply the Rasch model to an analysis of the
      psychometric properties of the PPVT-III Form A items with struggling adult
      readers.  METHODS: The PPVT-IIIA was administered to 229 African-American adults
      whose isolated word reading skills were between third and fifth grades.
      Conformity of the adults' performance on the PPVT-III items was evaluated using
      the Winsteps software.  RESULTS: Analysis of all PPVT-IIIA items combined did not
      fully support its use as a useful measure of receptive vocabulary for struggling
      adult readers who were African Americans. To achieve an adequate model fit, items
      73 through item 156 were analyzed. The items analyzed showed adequate internal
      consistency reliability, unidimensionality, and freedom from differential item
      functioning for ability, gender, and age, with a minor modification.  DISCUSSION:
      With an appropriate treatment of misfit items, the results supported the
      measurement properties, internal consistency reliability, unidimensionality of
      the PPVT-IIIA items, and measurement invariance of the test across subgroups of
      ability, age, and gender.

PMID- 22639556
TI  - Electrostatically Embedded Many-Body Expansion for Neutral and Charged
      Metalloenzyme Model Systems.
AB  - The electrostatically embedded many-body (EE-MB) method has proven accurate for
      calculating cohesive and conformational energies in clusters, and it has recently
      been extended to obtain bond dissociation energies for metal-ligand bonds in
      positively charged inorganic coordination complexes. In the present paper, we
      present four key guidelines that maximize the accuracy and efficiency of EE-MB
      calculations for metal centers. Then, following these guidelines, we show that
      the EE-MB method can also perform well for bond dissociation energies in a
      variety of neutral and negatively charged inorganic coordination systems
      representing metalloenzyme active sites, including a model of the catalytic site
      of the zinc-bearing anthrax toxin lethal factor, a popular target for drug
      development. In particular, we find that the electrostatically embedded three
      body (EE-3B) method is able to reproduce conventionally calculated bond-breaking
      energies in a series of pentacoordinate and hexacoordinate zinc-containing
      systems with an average absolute error (averaged over 25 cases) of only 0.98
      kcal/mol.

PMID- 22639555
TI  - Modeling Protein-Ligand Binding by Mining Minima.
AB  - We present the first application of the mining minima algorithm to protein-small
      molecule binding. This end-point approach use an empirical force field and
      implicit solvent models, treats the protein binding-site as fully flexible and
      estimates free energies as sums over local energy wells. The calculations are
      found to yield encouraging agreement with experiment for three sets of HIV
      1protease inhibitors and a set of phosphodiesterase 10a inhibitors. The
      contributions of various aspects of the model to its accuracy are examined, and
      the Poisson-Boltzmann correction is found to be the most critical. Interestingly,
      the computed changes in configurational entropy upon binding fall roughly along
      the same entropy-energy correlation previously observed for smaller host-guest
      systems. Strengths and weaknesses of the method are discussed, as are the
      prospects for enhancing accuracy and speed.

PMID- 22639557
TI  - Calculation of SAR for Transmit Coil Arrays.
AB  - Transmit coil arrays allowing independent control of individual coil drives
      facilitate adjustment of the B(1) field distribution, but when the B(1) field
      distribution is changed the electric field and SAR distributions are also
      altered. This makes safety evaluation of the transmit array a challenging problem
      because there are potentially an infinite number of possible field distributions
      in the sample. Local SAR levels can be estimated with numerical calculations, but
      it is not practical to perform separate full numerical calculations for every
      current distribution of interest. Here we evaluate superposition of separate
      electric field calculations-one for each coil-for predicting SAR in a full
      numerical calculation where all coils are driven simultaneously. It is important
      to perform such an evaluation because the effects of coil coupling may alter the
      result. It is shown that while there is good agreement between the superimposed
      and simultaneous drive results when using current sources in the simulations, the
      agreement is not as good when voltage sources are used. Finally, we compare
      maximum local SAR levels for B(1) field distributions that are either unshimmed
      or shimmed over one of three regions of interest. When B(1) field homogeneity is
      improved in a small region of interest without regard for SAR, the maximum local
      SAR can become very high.

PMID- 22639558
TI  - The Impact of Household Investments on Early Child Neurodevelopment and on Racial
      and Socioeconomic Developmental Gaps - Evidence from South America.

PMID- 22639559
TI  - [Epidemiological profile of children burns admitted at the National Center for
      Brules, Morocco].
AB  - This retrospective study was performed in order to analyse the epidemiology and
      aetiology of 543 cases of paediatric burns and to determine the elements that
      might have contributed to their prevention, which remains the treatment of choice
      for this pathology. The paediatric hospitalization rate for burns was 45.7% (mean
      age, 4.25 yr), the highest proportion of patients (42.5%) being in the 1-5 yr age
      group. The male/female ratio in all age groups was 1.7/1. The environment where
      burn injury most commonly occurred was the home (85.1%), and with accidental
      causes, accounting for 96.5% of the causes (mainly liquids, 69.3%). The mean
      percentage of burned body surface area was 21% with a total burned body surface
      area of >= 20% in 52.3% of cases. The upper limbs (79.1%) were the most affected
      body site; and the children were referred from other hospitals in more than 6 h
      in 65.5% of cases. The mortality rate was 13.2%

PMID- 22639561
TI  - Management of a clinical and surgical centre in rural Cambodia (2006-2011).
AB  - The activities of the Bambino Gesu Paediatric Clinical and Surgical Centre Takeo
      in Cambodia started in May 2006, after the signature of a formal agreement
      between the Royal Government of Cambodia and the hospital. The paediatric centre
      is currently composed of an out-patients section with diagnostic ultrasound
      facilities and an obstetrics and gynaecology section, 3 consulting rooms, 20 beds
      for clinical activities, 13 beds for surgery, 7 beds for the paediatric intensive
      care unit, 2 dressing rooms, 1 out-patients sterile section, a library for off-
      and on-line consultation, a playroom and laundry facilities, and an
      administration office. For the last five years its activity has neen steadily on
      the increase, and the local population are beginning to look on the Centre as a
      full-scale local and regional referral hospital. From the 190 cases handled in
      2006, the Centre increased to 669 surgical procedures in 2010 and 341 in the
      first four months of 2011, with good prospects of exceeding 1000 operations
      before the end of 2012. Takeo Centre also developed a Mobile Clinic Project to
      assist children directly in rural areas lacking health facilities. Today the
      Centre is a new reality in Cambodia's healthcare system.

PMID- 22639560
TI  - Thermal injury to the hand: review of the literature.
AB  - This paper is a comprehensive review of hand burn injuries. The different
      classifications of thermal burns, out- and inpatient care, indications for
      escharotomies as well as surgical management, skin substitutes, and paediatric
      hand burns are thoroughly reviewed.

PMID- 22639562
TI  - Applicability of new supervised statistical models to assess burn injury
      patterns, outcomes, and their interrelationship.
AB  - The aim of the study was to investigate the possibility of using supervised
      statistical models to assess burn injury patterns, outcomes and their
      interrelationship. Using burn study data, a preliminary principal component
      analysis was carried out and two separate clusters were observed. Observations
      were split into two classes and analysed by partial least squares (PLS)
      regression discriminant analysis to assess possible predictors of each class. To
      assess predictors of total body surface area burned (TBSA), the orthogonal
      projections to latent structures (OPLS) model was used after PLS regression. The
      identified classes were later designated as high-risk burn victims and low-risk
      burn victims. Female gender fell into the high-risk class. Many possible
      predictors were found to be associated with burn injury extent, after modelling
      the natural logarithm of TBSA by OPLS. The fitted model explained 76% of
      variation in Y. It excluded up to 9% of orthogonal variation captured in two
      orthogonal components. This seems to be the first application of the OPLS model
      in public health epidemiology. The results of this study were promising regarding
      the use of supervised models in injury pattern analysis.

PMID- 22639563
TI  - Burn treatment framework in Israel.
AB  - The treatment and hospitalization policies in various hospitals in Israel are
      influenced by injury severity and by the existence or non-existence of a
      designated burn treatment body. Severely injured burn victims requiring
      designated burn treatment are referred to one of Israel's five major burn units
      located in the highest level trauma centres that have an advanced burn treatment
      infrastructure. This national distribution of burn centres ensures designated
      treatment availability in various areas according to Israeli demographics,
      geography, and security threats. Israel does not have an obligatory burn report
      policy. Implementation of a national burn repository such as that in the USA will
      be able to give burn treatment specialists in our country a basis for comparison
      of treatment standards and allow for better care for burn victims. The Israeli
      Burn Association has a major role in the processes discussed in the manuscript.

PMID- 22639564
TI  - Comparison of the outcome of burn patients using acute-phase plasma base deficit.
AB  - Background. In recent years, plasma base deficit has been used as a marker to
      determine the status of tissue perfusion in trauma patients and also to predict
      the outcome of these patients. This study was performed to investigate the effect
      of plasma base deficit in predicting burn patient outcome. Methods. This
      prospective cohort study was performed from October 2009 to October 2010 in the
      acute phase of burn patients who were admitted within 6 h post-injury to Motahari
      Burn Hospital in Iran. The patients were divided into two groups based on the
      plasma base deficit in the first 24 h post-injury: group A, in which the mean
      plasma base deficit was less than or equal to -6 (more negative), and group B, in
      which the mean plasma base deficit greater than -6. Statistical analysis was
      performed using SPSS v.16 software. Results. Thirty-eight patients were enrolled
      in each group. The mean plasma base deficit in group A (-7.76 +/- 2.18 mmol) was
      significantly less than that in group B (-1.19 +/- 2.82) mmol (p < 0.05).
      Although there was no significant difference between the mean of fluid
      resuscitation and urine output in the first 24 h after injury between the two
      groups (p > 0.05) and despite removal of interfering factors, there were
      significant differences between the systemic inflammatory response syndrome and
      the multiple organ dysfunction syndrome score and the percentage of sepsis
      between the two groups (p < 0.05). The mortality rate in group A (63.2%) was
      significantly higher than that in group B (36.8%) (p > 0.05). Conclusion. The
      plasma base deficit can be used as a valuable marker in the resuscitation of burn
      patients, along with clinical criteria. Physiological indicators (burn
      percentage, age, and mucosal burns) are not sufficient to predict mortality and
      morbidity in burn patients, and it is necessary to investigate the role of
      biochemical markers such as base deficit in determining the final outcome of burn
      patients.

PMID- 22639565
TI  - The overall patterns of burns.
AB  - Burn patterns differ across the whole world and not only in relation to lack of
      education, overcrowding, and poverty. Cultures, habits, traditions, psychiatric
      illness, and epilepsy are strongly correlated to burn patterns. However, burns
      may also occur because of specific religious beliefs and activities, social
      events and festivals, traditional medical practices, occupational activities, and
      war.

PMID- 22639566
TI  - Is expansion of artificial dermis a reliable reconstructive option?
AB  - Reconstruction of full-thickness defects with the use of artificial dermis has
      been well established in the recent literature. The capacity of artificial dermis
      to expand over a period of years, months, or even days is described. Three such
      cases are reported. Two female patients, aged 21 and 30 years, with post-burn
      contractures of the chest with right breast hypoplasia and abdominal wall post
      burn contractures respectively, and a 14-year-old male with a giant congenital
      naevus on the forearm, are presented. After excision of the contractures and the
      congenital naevus, the patients underwent staged reconstruction with the use of
      artificial dermal template and split-thickness skin autografts at monthly
      intervals. The 21-yr-old female also had a tissue expander placed submuscularly
      which six months later was replaced by a permanent silicone implant. Gradual
      expansion of artificial dermis within three weeks resulted in reconstruction of a
      breast of natural shape, size, and volume. In the second patient the artificial
      dermis was expanded over a period of months, until full-term pregnancy, while the
      third patient took years to achieve expansion naturally as he grew up. In
      conclusion, artificial dermis can be expanded over various periods of time (days
      to years), providing a reliable and safe alternative reconstructive method,
      particularly in areas where expansion is an absolute necessity for a good
      functional and aesthetic result.

PMID- 22639568
TI  - The European Journal of Ageing in the European Year for Active Ageing.

PMID- 22639570
TI  - The grand challenges in functional plant ecology.

PMID- 22639569
TI  - Acetylcholinesterase loosens the brain's cholinergic anti-inflammatory response
      and promotes epileptogenesis.
AB  - Recent studies show a key role of brain inflammation in epilepsy. However, the
      mechanisms controlling brain immune response are only partly understood. In the
      periphery, acetylcholine (ACh) release by the vagus nerve restrains inflammation
      by inhibiting the activation of leukocytes. Recent reports suggested a similar
      anti-inflammatory effect for ACh in the brain. Since brain cholinergic
      dysfunctions are documented in epileptic animals, we explored changes in brain
      cholinergic gene expression and associated immune response during pilocarpine
      induced epileptogenesis. Levels of acetylcholinesterase (AChE) and inflammatory
      markers were measured using real-time RT-PCR, in-situ hybridization and
      immunostaining in wild type (WT) and transgenic mice over-expressing the
      "synaptic" splice variant AChE-S (TgS). One month following pilocarpine, mice
      were video-monitored for spontaneous seizures. To test directly the effect of ACh
      on the brain's innate immune response, cytokines expression levels were measured
      in acute brain slices treated with cholinergic agents. We report a robust up
      regulation of AChE as early as 48 h following pilocarpine-induced status
      epilepticus (SE). AChE was expressed in hippocampal neurons, microglia, and
      endothelial cells but rarely in astrocytes. TgS mice overexpressing AChE showed
      constitutive increased microglial activation, elevated levels of pro-inflammatory
      cytokines 48 h after SE and accelerated epileptogenesis compared to their WT
      counterparts. Finally we show a direct, muscarine-receptor dependant, nicotine
      receptor independent anti-inflammatory effect of ACh in brain slices maintained
      ex vivo. Our work demonstrates for the first time, that ACh directly suppresses
      brain innate immune response and that AChE up-regulation after SE is associated
      with enhanced immune response, facilitating the epileptogenic process. Our
      results highlight the cholinergic system as a potential new target for the
      prevention of seizures and epilepsy.

PMID- 22639571
TI  - Plant cell biology: with grand challenges come great possibilities.

PMID- 22639572
TI  - Grand challenges in plant nutrition.

PMID- 22639573
TI  - The green proteome: challenges in plant proteomics.

PMID- 22639574
TI  - Sweets - the missing sugar efflux carriers.

PMID- 22639575
TI  - No evidence for "break-induced replication" in a higher plant - but break-induced
      conversion may occur.
AB  - "Break-induced replication" (BIR) is considered as one way to repair DNA double
      strand breaks (DSBs). BIR is defined as replication of the proximal break-ends up
      to the end of the broken chromosome using an undamaged (homologous) double
      stranded template and mimicking a non-reciprocal translocation. This phenomenon
      was detected by genetic experiments in yeast. BIR is assumed to occur also in
      mammals, but experimental evidence is not yet at hand. We have studied
      chromosomes of the field bean, Vicia faba L., with respect to the occurrence of
      BIR after DSB induction during S and G2 phase. Simultaneous incorporation of the
      base analog ethynyldeoxyuridine (EdU) revealed no chromosomal replication pattern
      indicative of BIR. Thus, if occurring at all, BIR does not play a major role in
      DSB repair in higher plants with large chromosome arms. However, the frequency of
      interstitial asymmetric EdU incorporation within heterochromatic regions, visible
      on metaphase chromosomes, increased after chromosome breakage during S and G2
      phase. Such asymmetric labeling could be interpreted as conservative replication
      up to the next replicon, circumventing a DSB, and yielding an interstitial
      conversion-like event.

PMID- 22639577
TI  - Epigenetics: Biology's Quantum Mechanics.
AB  - The perspective presented here is that modern genetics is at a similar stage of
      development as were early formulations of quantum mechanics theory in the 1920s
      and that in 2010 we are at the dawn of a new revolution in genetics that promises
      to enrich and deepen our understanding of the gene and the genome. The
      interrelationships and interdependence of two views of the gene - the molecular
      biological view and the epigenetic view - are explored, and it is argued that the
      classical molecular biological view is incomplete without incorporation of the
      epigenetic perspective and that in a sense the molecular biological view has been
      evolving to include the epigenetic view. Intriguingly, this evolution of the
      molecular view toward the broader and more inclusive epigenetic view of the gene
      has an intriguing, if not precise, parallel in the evolution of concepts of
      atomic physics from Newtonian mechanics to quantum mechanics that are interesting
      to consider.

PMID- 22639576
TI  - Programmed Cell Death in the Leaves of the Arabidopsis Spontaneous Necrotic Spots
      (sns-D) Mutant Correlates with Increased Expression of the Eukaryotic Translation
      Initiation Factor eIF4B2.
AB  - From a pool of transgenic Arabidopsis (Arabidopsis thaliana) plants harboring an
      activator T-DNA construct, one mutant was identified that developed spontaneous
      necrotic spots (sns-D) on the rosette leaves under aseptic conditions. The sns-D
      mutation is dominant and homozygous plants are embryo lethal. The mutant produced
      smaller rosettes with a different number of stomata than the wild-type. DNA
      fragmentation in the nuclei of cells in the necrotic spots and a significant
      increase of caspase-3 and caspase-6 like activities in sns-D leaf extracts
      indicated that the sns-D mutation caused programmed cell death (PCD). The
      integration of the activator T-DNA caused an increase of the expression level of
      At1g13020, which encodes the eukaryotic translation initiation factor eIF4B2. The
      expression level of eIF4B2 was positively correlated with the severity of sns-D
      mutant phenotype. Overexpression of the eIF4B2 cDNA mimicked phenotypic traits of
      the sns-D mutant indicating that the sns-D mutant phenotype is indeed caused by
      activation tagging of eIF4B2. Thus, incorrect regulation of translation
      initiation may result in PCD.

PMID- 22639578
TI  - Real-Time Imaging of Leaf Apoplastic pH Dynamics in Response to NaCl Stress.
AB  - Knowledge concerning apoplastic ion concentrations is important for the
      understanding of many processes in plant physiology. Ion-sensitive fluorescent
      probes in combination with quantitative imaging techniques offer opportunities to
      localize, visualize, and quantify apoplastic ion dynamics in situ. The
      application of this technique to the leaf apoplast is complicated because of
      problems associated with dye loading. We demonstrate a more sophisticated dye
      loading procedure that enables the mapping of spatial apoplastic ion gradients
      over a period of 3 h. The new technique has been used for the real-time
      monitoring of pH dynamics within the leaf apoplast in response to NaCl stress
      encountered by the roots.

PMID- 22639579
TI  - Grand challenge: viewing transporter function in a pointillist landscape.

PMID- 22639580
TI  - Canopy stomatal conductance following drought, disturbance, and death in an
      upland oak/pine forest of the new jersey pine barrens, USA.
AB  - Stomatal conductance controls carbon and water fluxes in forest ecosystems.
      Therefore, its accurate characterization in land-surface flux models is
      necessary. Sap-flux scaled canopy conductance was used to evaluate the effect of
      drought, disturbance, and mortality of three oak species (Quercus prinus, Q.
      velutina, and Q. coccinea) in an upland oak/pine stand in the New Jersey Pine
      Barrens from 2005 to 2008. Canopy conductance (G(C)) was analyzed by performing
      boundary line analysis and selecting for the highest value under a given light
      condition. Regressing G(C) with the driving force vapor pressure deficit (VPD)
      resulted in reference canopy conductance at 1 kPa VPD (G(Cref)). Predictably,
      drought in 2006 caused G(Cref) to decline. Q. prinusG(Cref) was least affected,
      followed by Q. coccinea, with Q. velutina having the highest reductions in
      G(Cref). A defoliation event in 2007 caused G(Cref) to increase due to reduced
      leaf area and a possible increase in water availability. In Q. prinus, G(Cref)
      quadrupled, while doubling in Q. velutina, and increasing by 50% in Q. coccinea.
      Tree mortality in 2008 led to higher G(Cref) in the remaining Q. prinus but not
      in Q. velutina or Q. coccinea. Comparing light response curves of canopy
      conductance (G(Cref)) and stomatal conductance (g(S)) derived from gas-exchange
      measurements showed marked differences in behavior. Canopy G(Cref) failed to
      saturate under ambient light conditions whereas leaf-level g(S) saturated at
      1,200 MUmol m(-2) s(-1). The results presented here emphasize the differential
      responses of leaf and canopy-level conductance to saturating light conditions and
      the effects of various disturbances (drought, defoliation, and mortality) on the
      carbon and water balance of an oak-dominated forest.

PMID- 22639581
TI  - Asymmetric distribution of gene expression in the centromeric region of rice
      chromosome 5.
AB  - There is controversy as to whether gene expression is silenced in the functional
      centromere. The complete genomic sequences of the centromeric regions in higher
      eukaryotes have not been fully elucidated, because the presence of highly
      repetitive sequences complicates many aspects of genomic sequencing. We performed
      resequencing, assembly, and sequence finishing of two P1-derived artificial
      chromosome clones in the centromeric region of rice (Oryza sativa L.) chromosome
      5 (Cen5). The pericentromeric region, where meiotic recombination is silenced, is
      located at the center of chromosome 5 and is 2.14 Mb long; a total of six
      restriction-fragment-length polymorphism markers (R448, C1388, S20487S, E3103S,
      C53260S, and R2059) genetically mapped at 54.6 cM were located in this region. In
      the pericentromeric region, 28 genes were annotated on the short arm and 45 genes
      on the long arm. To quantify all transcripts in this region, we performed massive
      parallel sequencing of mRNA. Transcriptional density (total length of transcribed
      region/length of the genomic region) and expression level (number of uniquely
      mapped reads/length of transcribed region) were calculated on the basis of the
      mapped reads on the rice genome. Transcriptional density and expression level
      were significantly lower in Cen5 than in the average of the other chromosomal
      regions. Moreover, transcriptional density in Cen5 was significantly lower on the
      short arm than on the long arm; the distribution of transcriptional density was
      asymmetric. The genomic sequence of Cen5 has been integrated into the most
      updated reference rice genome sequence constructed by the International Rice
      Genome Sequencing Project.

PMID- 22639583
TI  - Dynamics of depletion and replenishment of water storage in stem and roots of
      black spruce measured by dendrometers.
AB  - In the short term, trees rely on the internal storage of water because it affects
      their ability to sustain photosynthesis and growth. However, water is not rapidly
      available for transpiration from all the compartments of the plant and the living
      tissues of the stem act as a buffer to preclude low water potentials during peaks
      of transpiration. In this paper, electronic dendrometers were used from mid-June
      to mid-September 2008 to compare the radius variations in stem and roots of black
      spruce [Picea mariana (Mill.) B.S.P.] in two sites of the boreal forest of
      Quebec, Canada, with different soil characteristics and water retention. The
      duration of the daily cycles was similar between sites and measurement heights
      but greater amplitudes of contraction and expansion were observed on the stem and
      in the site with the shallowest soil organic layer. The expansion phase had
      higher amplitudes and lasted longer than contraction. On average, the contraction
      phase occurred between 07:00 and 16:30 (legal time), while expansion lasted 14.5
      h. The roots in the site with the deepest organic layer showed a wider variation
      in the onset of contraction, which could be as late as 13:00. The probability of
      observing the contraction phase depended on precipitation. With a precipitation
      <0.5 mm (h-1), the bivariate posterior probabilities estimated >60% probability
      of observing contraction between 05:00 and 21:00, decreasing to 20% with
      precipitation >1.1 mm h(-1). These findings demonstrated that the depth of the
      organic layer plays an important role in maintaining the internal water reserve
      of trees. The dynamics of water depletion and replenishment can modify the water
      potential of xylem and cell turgor during the enlargement phase, thus affecting
      radial growth. Changes in temperature and precipitation regime could influence
      the dynamics of internal water storage in trees growing on shallower and drier
      soils.

PMID- 22639582
TI  - Protein-Protein Interaction Network and Subcellular Localization of the
      Arabidopsis Thaliana ESCRT Machinery.
AB  - The endosomal sorting complex required for transport (ESCRT) consists of several
      multi-protein subcomplexes which assemble sequentially at the endosomal surface
      and function in multivesicular body (MVB) biogenesis. While ESCRT has been
      relatively well characterized in yeasts and mammals, comparably little is known
      about ESCRT in plants. Here we explored the yeast two-hybrid protein interaction
      network and subcellular localization of the Arabidopsis thaliana ESCRT machinery.
      We show that the Arabidopsis ESCRT interactome possesses a number of protein
      protein interactions that are either conserved in yeasts and mammals or distinct
      to plants. We show also that most of the Arabidopsis ESCRT proteins examined at
      least partially localize to MVBs in plant cells when ectopically expressed on
      their own or co-expressed with other interacting ESCRT proteins, and some also
      induce abnormal MVB phenotypes, consistent with their proposed functional role(s)
      as part of the ESCRT machinery in Arabidopsis. Overall, our results help define
      the plant ESCRT machinery by highlighting both conserved and unique features when
      compared to ESCRT in other evolutionarily diverse organisms, providing a
      foundation for further exploration of ESCRT in plants.

PMID- 22639584
TI  - Large-scale co-expression approach to dissect secondary cell wall formation
      across plant species.
AB  - Plant cell walls are complex composites largely consisting of carbohydrate-based
      polymers, and are generally divided into primary and secondary walls based on
      content and characteristics. Cellulose microfibrils constitute a major component
      of both primary and secondary cell walls and are synthesized at the plasma
      membrane by cellulose synthase (CESA) complexes. Several studies in Arabidopsis
      have demonstrated the power of co-expression analyses to identify new genes
      associated with secondary wall cellulose biosynthesis. However, across-species
      comparative co-expression analyses remain largely unexplored. Here, we compared
      co-expressed gene vicinity networks of primary and secondary wall CESAsin
      Arabidopsis, barley, rice, poplar, soybean, Medicago, and wheat, and identified
      gene families that are consistently co-regulated with cellulose biosynthesis. In
      addition to the expected polysaccharide acting enzymes, we also found many gene
      families associated with cytoskeleton, signaling, transcriptional regulation,
      oxidation, and protein degradation. Based on these analyses, we selected and
      biochemically analyzed T-DNA insertion lines corresponding to approximately
      twenty genes from gene families that re-occur in the co-expressed gene vicinity
      networks of secondary wall CESAs across the seven species. We developed a
      statistical pipeline using principal component analysis and optimal clustering
      based on silhouette width to analyze sugar profiles. One of the mutants,
      corresponding to a pinoresinol reductase gene, displayed disturbed xylem
      morphology and held lower levels of lignin molecules. We propose that this type
      of large-scale co-expression approach, coupled with statistical analysis of the
      cell wall contents, will be useful to facilitate rapid knowledge transfer across
      plant species.

PMID- 22639585
TI  - Organ size regulation in plants: insights from compensation.
AB  - The regulation of organ size in higher organisms is a fundamental issue in
      developmental biology. In flowering plants, a phenomenon called "compensation"
      has been observed where a cell proliferation defect in developing leaf primordia
      triggers excessive cell expansion. As a result, final leaf size is not
      significantly reduced compared to that expected from the reduction in leaf cell
      numbers. Recent genetic studies have revealed several key features of the
      compensation phenomenon. Compensation is induced either cell autonomously or non
      cell autonomously depending on the trigger that impairs cell proliferation; a
      certain type of compensation is induced only when cell proliferation is impaired
      beyond a threshold level. Excessive cell expansion is achieved by either an
      increased cell expansion rate or a prolonged period of cell expansion via genetic
      pathways that are also required for normal cell expansion. These results indicate
      that cell proliferation and cell expansion are coordinated through multiple
      pathways during leaf size determination. Further classification of compensation
      pathways and their characterization at the molecular level will provide a deeper
      understanding of organ size regulation.

PMID- 22639586
TI  - Triterpenoid biosynthesis and engineering in plants.
AB  - Triterpenoid saponins are a diverse group of natural products in plants and are
      considered defensive compounds against pathogenic microbes and herbivores.
      Because of their various beneficial properties for humans, saponins are used in
      wide-ranging applications in addition to medicinally. Saponin biosynthesis
      involves three key enzymes: oxidosqualene cyclases, which construct the basic
      triterpenoid skeletons; cytochrome P450 monooxygenases, which mediate oxidations;
      and uridine diphosphate-dependent glycosyltransferases, which catalyze
      glycosylations. The discovery of genes committed to saponin biosynthesis is
      important for the stable supply and biotechnological application of these
      compounds. Here, we review the identified genes involved in triterpenoid
      biosynthesis, summarize the recent advances in the biotechnological production of
      useful plant terpenoids, and discuss the bioengineering of plant triterpenoids.

PMID- 22639587
TI  - Microtubule Reorganization during Mitosis and Cytokinesis: Lessons Learned from
      Developing Microgametophytes in Arabidopsis Thaliana.
AB  - In angiosperms, mitosis and cytokinesis take place in the absence of structurally
      defined microtubule-organizing centers and the underlying mechanisms are largely
      unknown. In the spindle and phragmoplast, microtubule reorganization depends on
      microtubule-interacting factors like the gamma-tubulin complex. Because of their
      critical functions in cell division, loss-of-function mutations in the
      corresponding genes are often homozygous or sporophytic lethal. However, a number
      of mutations like gem1, gcp2, and nedd1 can be maintained in heterozygous mutants
      in Arabidopsis thaliana. When mutant microspores produced by a heterozygous
      parent undergo pollen mitosis I, they are amenable for phenotypic
      characterization by fluorescence microscopy. The results would allow us to
      pinpoint at specific functions of particular proteins in microtubule
      reorganization that are characteristic to specific stages of mitosis and
      cytokinesis. Conclusions made in the developing microgametophytes can be
      extrapolated to somatic cells regarding mechanisms that regulate nuclear
      migration, spindle pole formation, phragmoplast assembly, and cell division plane
      determination.

PMID- 22639588
TI  - Potential Maternal Effects of Elevated Atmospheric CO(2) on Development and
      Disease Severity in a Mediterranean Legume.
AB  - Global change can greatly affect plant populations both directly by influencing
      growing conditions and indirectly by maternal effects on development of
      offspring. More information is needed on transgenerational effects of global
      change on plants and their interactions with pathogens. The current study
      assessed potential maternal effects of atmospheric CO(2) enrichment on
      performance and disease susceptibility of first-generation offspring of the
      Mediterranean legume Onobrychis crista-galli. Mother plants were grown at three
      CO(2) concentrations, and the study focused on their offspring that were raised
      under common ambient climate and CO(2). In addition, progeny were exposed to
      natural infection by the fungal pathogen powdery mildew. In one out of 3 years,
      offspring of high-CO(2) treatments (440 and 600 ppm) had lower shoot biomass and
      reproductive output than offspring of low-CO(2) treatment (280 ppm). Disease
      severity in a heavy-infection year was higher in high-CO(2) than in low-CO(2)
      offspring. However, some of the findings on maternal effects changed when the
      population was divided into two functionally diverging plant types
      distinguishable by flower color (pink, Type P; white, Type W). Disease severity
      in a heavy-infection year was higher in high-CO(2) than in low-CO(2) progeny in
      the more disease-resistant (Type P), but not in the more susceptible plant type
      (Type W). In a low-infection year, maternal CO(2) treatments did not differ in
      disease severity. Mother plants of Type P exposed to low CO(2) produced larger
      seeds than all other combinations of CO(2) and plant type, which might contribute
      to higher offspring performance. This study showed that elevated CO(2)
      potentially exerts environmental maternal effects on performance of progeny and,
      notably, also on their susceptibility to natural infection by a pathogen.
      Maternal effects of global change might differently affect functionally divergent
      plant types, which could impact population fitness and alter plant communities.

PMID- 22639589
TI  - Quantifying green life: grand challenges in plant biophysics and modeling.

PMID- 22639590
TI  - Tobacco Transcription Factor NtWRKY12 Interacts with TGA2.2 in vitro and in vivo.
AB  - The promoter of the salicylic acid-inducible PR-1a gene of Nicotiana tabacum
      contains binding sites for transcription factor NtWRKY12 (WK-box at position 
      564) and TGA factors (as-1-like element at position -592). Transactivation
      experiments in Arabidopsis protoplasts derived from wild type, npr1-1, tga256,
      and tga2356 mutant plants revealed that NtWRKY12 alone was able to induce a PR
      1a::beta-glucuronidase (GUS) reporter gene to high levels, independent of co
      expressed tobacco NtNPR1, TGA2.1, TGA2.2, or endogenous Arabidopsis NPR1,
      TGA2/3/5/6. By in vitro pull-down assays with GST and Strep fusion proteins and
      by Fluorescence Resonance Energy Transfer assays with protein-CFP and protein-YFP
      fusions in transfected protoplasts, it was shown that NtWRKY12 and TGA2.2 could
      interact in vitro and in vivo. Interaction of NtWRKY12 with TGA1a or TGA2.1 was
      not detectable by these techniques. A possible mechanism for the role of NtWRKY12
      and TGA2.2 in PR-1a gene expression is discussed.

PMID- 22639592
TI  - Elevated phosphorus impedes manganese acquisition by barley plants.
AB  - The occurrence of manganese (Mn) deficiency in cereal crops has increased in
      recent years. This coincides with increasing phosphorus (P) status of many soils
      due to application of high levels of animal manure and P-fertilizers. In order to
      test the hypothesis that elevated P my lead to Mn deficiency we have here
      conducted a series of hydroponics and soil experiments examining how the P supply
      affects the Mn nutrition of barley. Evidence for a direct negative interaction
      between P and Mn during root uptake was obtained by on-line inductively coupled
      plasma mass spectrometry (ICP-MS). Addition of a pulse of KH(2)PO(4) rapidly and
      significantly reduced root Mn uptake, while a similar concentration of KCl had no
      effect. Addition of a P pulse to the same nutrient solution without plants did
      not affect the concentration of Mn, revealing that no precipitation of Mn-P
      species was occurring. Barley plants growing at a high P supply in hydroponics
      with continuous replenishment of Mn(2+) had up to 50% lower Mn concentration in
      the youngest leaves than P limited plants. This P-induced depression of foliar Mn
      accelerated the development of Mn deficiency as evidenced by a marked change in
      the fluorescence induction kinetics of chlorophyll a. Also plants growing in soil
      exhibited lower leaf Mn concentrations in response to elevated P. In contrast,
      leaf concentrations of Fe, Cu, and N increased with the P supply, supporting that
      the negative effect of P on Mn acquisition was specific rather than due to a
      general dilution effect. It is concluded that elevated P supply directly
      interferes with Mn uptake in barley roots and that this negative interaction can
      induce Mn deficiency in the shoot. This finding has major implications in
      commercial plant production where many soils have high P levels.

PMID- 22639591
TI  - Mining disease-resistance genes in roses: functional and molecular
      characterization of the rdr1 locus.
AB  - The interaction of roses with the leaf spot pathogen Diplocarpon rosae (the cause
      of black spot on roses) is an interesting pathosystem because it involves a long
      lived woody perennial, with life history traits very different from most model
      plants, and a hemibiotrophic pathogen with moderate levels of gene flow. Here we
      present data on the molecular structure of the first monogenic dominant
      resistance gene from roses, Rdr1, directed against one isolate of D. rosae.
      Complete sequencing of the locus carrying the Rdr1 gene resulted in a sequence of
      265,477 bp with a cluster of nine highly related TIR-NBS-LRR (TNL) candidate
      genes. After sequencing revealed candidate genes for Rdr1, we implemented a gene
      expression analysis and selected five genes out of the nine TNLs. We then
      silenced the whole TNL gene family using RNAi (Rdr1-RNAi) constructed from the
      most conserved sequence region and demonstrated a loss of resistance in the
      normally resistant genotype. To identify the functional TNL gene, we further
      screened the five TNL candidate genes with a transient leaf infiltration assay.
      The transient expression assay indicated a single TNL gene (muRdr1H), partially
      restoring resistance in the susceptible genotype. Rdr1 was found to localize
      within the muRdr1 gene family; the genes within this locus contain characteristic
      motifs of active TNL genes and belong to a young cluster of R genes. The
      transient leaf assay can be used to further analyze the rose black spot
      interaction and its evolution, extending the analyses to additional R genes and
      to additional pathogenic types of the pathogen.

PMID- 22639593
TI  - Silencing beta1,2-xylosyltransferase in Transgenic Tomato Fruits Reveals xylose
      as Constitutive Component of Ige-Binding Epitopes.
AB  - Complex plant N-glycans containing beta1,2-xylose and core alpha1,3-fucose are
      regarded as the major class of the so-called "carbohydrate cross-reactive
      determinants" reactive with IgE antibodies in sera of many allergic patients, but
      their clinical relevance is still under debate. Plant glycosyltransferases,
      beta1,2-xylosyltransferase (XylT), and core alpha1,3-fucosyltransferase (FucT)
      are responsible for the transfer of beta1,2-linked xylose and core alpha1,3
      linked fucose residues to N-glycans of glycoproteins, respectively. To test the
      clinical relevance of beta1,2-xylose-containing epitopes, expression of the
      tomato beta1,2-xylosyltransferase was down-regulated by RNA interference (RNAi)
      in transgenic plants. Fruits harvested from these transgenic plants were analyzed
      for accumulation of XylT mRNA, abundance of beta1,2-xylose epitopes and their
      allergenic potential. Based on quantitative real-time PCR analysis XylT mRNA
      levels were reduced up to 10-fold in independent transgenic lines as compared to
      untransformed control, whereas no xylosylated N-glycans could be revealed by MS
      analysis. Immunoblotting using anti-xylose-specific IgG antibodies revealed a
      strong reduction of beta1,2-xylose-containing epitopes. Incubating protein
      extracts from untransformed controls and XylT_RNAi plants with sera from tomato
      allergic patients showed a patient-specific reduction in IgE-binding, indicating
      a reduced allergenic potential of XylT_RNAi tomato fruits, in vitro. To elucidate
      the clinical relevance of beta1,2-xylose-containing complex N-glycans skin prick
      tests were performed demonstrating a reduced responsiveness of tomato allergic
      patients, in vivo. This study provides strong evidence for the clinical relevance
      of beta1,2-xylose-containing epitopes in vivo.

PMID- 22639594
TI  - SLocX: Predicting Subcellular Localization of Arabidopsis Proteins Leveraging
      Gene Expression Data.
AB  - Despite the growing volume of experimentally validated knowledge about the
      subcellular localization of plant proteins, a well performing in silico
      prediction tool is still a necessity. Existing tools, which employ information
      derived from protein sequence alone, offer limited accuracy and/or rely on full
      sequence availability. We explored whether gene expression profiling data can be
      harnessed to enhance prediction performance. To achieve this, we trained several
      support vector machines to predict the subcellular localization of Arabidopsis
      thaliana proteins using sequence derived information, expression behavior, or a
      combination of these data and compared their predictive performance through a
      cross-validation test. We show that gene expression carries information about the
      subcellular localization not available in sequence information, yielding dramatic
      benefits for plastid localization prediction, and some notable improvements for
      other compartments such as the mitochondrion, the Golgi, and the plasma membrane.
      Based on these results, we constructed a novel subcellular localization
      prediction engine, SLocX, combining gene expression profiling data with protein
      sequence-based information. We then validated the results of this engine using an
      independent test set of annotated proteins and a transient expression of GFP
      fusion proteins. Here, we present the prediction framework and a website of
      predicted localizations for Arabidopsis. The relatively good accuracy of our
      prediction engine, even in cases where only partial protein sequence is available
      (e.g., in sequences lacking the N-terminal region), offers a promising
      opportunity for similar application to non-sequenced or poorly annotated plant
      species. Although the prediction scope of our method is currently limited by the
      availability of expression information on the ATH1 array, we believe that the
      advances in measuring gene expression technology will make our method applicable
      for all Arabidopsis proteins.

PMID- 22639595
TI  - Quantitative proteomic analysis of wheat cultivars with differing drought stress
      tolerance.
AB  - Using a series of multiplexed experiments we studied the quantitative changes in
      protein abundance of three Australian bread wheat cultivars (Triticum aestivum
      L.) in response to a drought stress. Three cultivars differing in their ability
      to maintain grain yield during drought, Kukri (intolerant), Excalibur (tolerant),
      and RAC875 (tolerant), were grown in the glasshouse with cyclic drought treatment
      that mimicked conditions in the field. Proteins were isolated from leaves of
      mature plants and isobaric tags were used to follow changes in the relative
      protein abundance of 159 proteins. This is the first shotgun proteomics study in
      wheat, providing important insights into protein responses to drought as well as
      identifying the largest number of wheat proteins (1,299) in a single study. The
      changes in the three cultivars at the different time points reflected their
      differing physiological responses to drought, with the two drought tolerant
      varieties (Excalibur and RAC875) differing in their protein responses. Excalibur
      lacked significant changes in proteins during the initial onset of the water
      deficit in contrast to RAC875 that had a large number of significant changes. All
      three cultivars had changes consistent with an increase in oxidative stress
      metabolism and reactive O(2) species (ROS) scavenging capacity seen through
      increases in superoxide dismutases and catalases as well as ROS avoidance through
      the decreases in proteins involved in photosynthesis and the Calvin cycle.

PMID- 22639596
TI  - Comparative Effects of Nitrogen Fertigation and Granular Fertilizer Application
      on Growth and Availability of Soil Nitrogen during Establishment of Highbush
      Blueberry.
AB  - A 2-year study was done to compare the effects of nitrogen (N) fertigation and
      granular fertilizer application on growth and availability of soil N during
      establishment of highbush blueberry (Vaccinium corymbosum L. "Bluecrop").
      Treatments included four methods of N application (weekly fertigation, split
      fertigation, and two non-fertigated controls) and four levels of N fertilizer (0,
      50, 100, and 150 kg.ha(-1) N). Fertigation treatments were irrigated by drip and
      injected with a liquid urea solution; weekly fertigation was applied once a week
      from leaf emergence to 60 d prior to the end of the season while split
      fertigation was applied as a triple-split from April to June. Non-fertigated
      controls were fertilized with granular ammonium sulfate, also applied as a triple
      split, and irrigated by drip or microsprinklers. Weekly fertigation produced the
      smallest plants among the four fertilizer application methods at 50 kg.ha(-1) N
      during the first year after planting but the largest plants at 150 kg.ha(-1) N in
      both the first and second year. The other application methods required less N to
      maximize growth but were less responsive than weekly fertigation to additional N
      fertilizer applications. In fact, 44-50% of the plants died when granular
      fertilizer was applied at 150 kg.ha(-1) N. By comparison, none of the plants died
      with weekly fertigation. Plant death with granular fertilizer was associated with
      high ammonium ion concentrations (up to 650 mg.L(-1)) and electrical conductivity
      (>3 dS.m(-1)) in the soil solution. Early results indicate that fertigation may
      be less efficient (i.e., less plant growth per unit of N applied) at lower N
      rates than granular fertilizer application but is also safer (i.e., less plant
      death) and promotes more growth when high amounts of N fertilizer is applied.

PMID- 22639597
TI  - Grand challenges in plant physiology: the underpinning of translational research.

PMID- 22639598
TI  - Gravity research on plants: use of single-cell experimental models.
AB  - Future space missions and implementation of permanent bases on Moon and Mars will
      greatly depend on the availability of ambient air and sustainable food supply.
      Therefore, understanding the effects of altered gravity conditions on plant
      metabolism and growth is vital for space missions and extra-terrestrial human
      existence. In this mini-review we summarize how plant cells are thought to
      perceive changes in magnitude and orientation of the gravity vector. The
      particular advantages of several single-celled model systems for gravity research
      are explored and an overview over recent advancements and potential use of these
      systems is provided.

PMID- 22639599
TI  - Latest news on Arabidopsis brassinosteroid perception and signaling.
AB  - Brassinosteroids (BRs) are plant hormones regulating growth and development. In
      interaction with other hormones, they are involved in environmental cue
      responses. The present model of the BR response pathway in Arabidopsis includes
      the perception of the hormone by the plasma membrane (PM) receptor
      brassinosteroid insensitive 1 (BRI1) and its hetero-oligomerization with the co
      receptor BRI1-associated receptor kinase 1 (BAK1), followed by the activation of
      a signaling-cascade finally resulting in the expression of BR-responsive genes.
      New findings have shed light on the receptor density in the PM and on the
      molecular mechanism of BR perception, which includes the hormone-induced
      formation of a platform in the BRI1 extracellular domain for interaction with
      BAK1. Furthermore, new knowledge on early, BRI1-initiated signaling events at the
      PM-cytoplasm interface has recently been gained. In addition, a fast BR response
      pathway that modifies the membrane potential and the expansion of the cell wall -
      both crucial processes preceding cell elongation growth - have been identified.
      In this review, these latest findings are summarized and discussed against the
      background of the present model of BRI1 signaling.

PMID- 22639600
TI  - Switching on Flowers: Transient LEAFY Induction Reveals Novel Aspects of the
      Regulation of Reproductive Development in Arabidopsis.
AB  - DEVELOPMENTAL FATE DECISIONS IN CELL POPULATIONS FUNDAMENTALLY DEPEND ON AT LEAST
      TWO PARAMETERS: a signal that is perceived by the cell and the intrinsic ability
      of the cell to respond to the signal. The same regulatory logic holds for phase
      transitions in the life cycle of an organism, for example the switch to
      reproductive development in flowering plants. Here we have tested the response of
      the monocarpic plant species Arabidopsis thaliana to a signal that directs flower
      formation, the plant-specific transcription factor LEAFY (LFY). Using transient
      steroid-dependent LEAFY (LFY) activation in lfy null mutant Arabidopsis plants,
      we show that the plant's competence to respond to the LFY signal changes during
      development. Very early in the life cycle, the plant is not competent to respond
      to the signal. Subsequently, transient LFY activation can direct primordia at the
      flanks of the shoot apical meristem to adopt a floral fate. Finally, the plants
      acquire competence to initiate the flower-patterning program in response to
      transient LFY activation. Similar to a perennial life strategy, we did not
      observe reprogramming of all primordia after perception of the transient signal,
      instead only a small number of meristems responded, followed by reversion to the
      prior developmental program. The ability to initiate flower formation and to
      direct flower patterning in response to transient LFY upregulation was dependent
      on the known direct LFY target APETALA1 (AP1). Prolonged LFY or activation could
      alter the developmental gradient and bypass the requirement for AP1. Prolonged
      high AP1 levels, in turn, can also alter the plants' competence. Our findings
      shed light on how plants can fine-tune important phase transitions and
      developmental responses.

PMID- 22639601
TI  - From models to crop species: caveats and solutions for translational
      metabolomics.
AB  - Although plant metabolomics is largely carried out on Arabidopsis it is
      essentially genome-independent, and thus potentially applicable to a wide range
      of species. However, transfer between species, or even between different tissues
      of the same species, is not facile. This is because the reliability of protocols
      for harvesting, handling and analysis depends on the biological features and
      chemical composition of the plant tissue. In parallel with the diversification of
      model species it is important to establish good handling and analytic practice,
      in order to augment computational comparisons between tissues and species. Liquid
      chromatography-mass spectrometry (LC-MS)-based metabolomics is one of the
      powerful approaches for metabolite profiling. By using a combination of different
      extraction methods, separation columns, and ion detection, a very wide range of
      metabolites can be analyzed. However, its application requires careful attention
      to exclude potential pitfalls, including artifactual changes in metabolite levels
      during sample preparation under variations of light or temperature and analytic
      errors due to ion suppression. Here we provide case studies with two different LC
      MS-based metabolomics platforms and four species (Arabidopsis thaliana,
      Chlamydomonas reinhardtii, Solanum lycopersicum, and Oryza sativa) that
      illustrate how such dangers can be detected and circumvented.

PMID- 22639602
TI  - Experimental flux measurements on a network scale.
AB  - Metabolic flux is a fundamental property of living organisms. In recent years,
      methods for measuring metabolic flux in plants on a network scale have evolved
      further. One major challenge in studying flux in plants is the complexity of the
      plant's metabolism. In particular, in the presence of parallel pathways in
      multiple cellular compartments, the core of plant central metabolism constitutes
      a complex network. Hence, a common problem with the reliability of the
      contemporary results of (13)C-Metabolic Flux Analysis in plants is the
      substantial reduction in complexity that must be included in the simulated
      networks; this omission partly is due to limitations in computational
      simulations. Here, I discuss recent emerging strategies that will better address
      these shortcomings.

PMID- 22639603
TI  - Aldehyde Dehydrogenases in Arabidopsis thaliana: Biochemical Requirements,
      Metabolic Pathways, and Functional Analysis.
AB  - Aldehyde dehydrogenases (ALDHs) are a family of enzymes which catalyze the
      oxidation of reactive aldehydes to their corresponding carboxylic acids. Here we
      summarize molecular genetic and biochemical analyses of selected ArabidopsisALDH
      genes. Aldehyde molecules are very reactive and are involved in many metabolic
      processes but when they accumulate in excess they become toxic. Thus activity of
      aldehyde dehydrogenases is important in regulating the homeostasis of aldehydes.
      Overexpression of some ALDH genes demonstrated an improved abiotic stress
      tolerance. Despite the fact that several reports are available describing a role
      for specific ALDHs, their precise physiological roles are often still unclear.
      Therefore a number of genetic and biochemical tools have been generated to
      address the function with an emphasis on stress-related ALDHs. ALDHs exert their
      functions in different cellular compartments and often in a developmental and
      tissue specific manner. To investigate substrate specificity, catalytic
      efficiencies have been determined using a range of substrates varying in carbon
      chain length and degree of carbon oxidation. Mutational approaches identified
      amino acid residues critical for coenzyme usage and enzyme activities.

PMID- 22639604
TI  - The Iron Assimilatory Protein, FEA1, from Chlamydomonas reinhardtii Facilitates
      Iron-Specific Metal Uptake in Yeast and Plants.
AB  - We demonstrate that the unique green algal iron assimilatory protein, FEA1, is
      able to complement the Arabidopsis iron-transporter mutant, irt1, as well as
      enhance iron accumulation in FEA1 expressing wild-type plants. Expression of the
      FEA1 protein reduced iron-deficient growth phenotypes when plants were grown
      under iron limiting conditions and enhanced iron accumulation up to fivefold
      relative to wild-type plants when grown in iron sufficient media. Using yeast
      iron-uptake mutants, we demonstrate that the FEA1 protein specifically
      facilitates the uptake of the ferrous form of iron. Significantly, the FEA1
      protein does not increase sensitivity to toxic concentrations of competing, non
      ferrous metals nor facilitate their (cadmium) accumulation. These results
      indicate that the FEA1 protein is iron specific consistent with the observation
      the FEA1 protein is overexpressed in cadmium stressed algae presumably to
      facilitate iron uptake. We propose that the FEA1 iron assimilatory protein has
      ideal characteristics for the iron biofortification of crops and/or for
      facilitated iron uptake in plants when they are grown in low iron, high pH soils,
      or soils that may be contaminated with heavy metals.

PMID- 22639605
TI  - Heavy Metals Need Assistance: The Contribution of Nicotianamine to Metal
      Circulation Throughout the Plant and the Arabidopsis NAS Gene Family.
AB  - Understanding the regulated inter- and intra-cellular metal circulation is one of
      the challenges in the field of metal homeostasis. Inside organisms metal ions are
      bound to organic ligands to prevent their uncontrolled reactivity and to increase
      their solubility. Nicotianamine (NA) is one of the important ligands. This non
      proteinogenic amino acid is synthesized by nicotianamine synthase (NAS). NA is
      involved in mobilization, uptake, transport, storage, and detoxification of
      metals. Much of the progress in understanding NA function has been achieved by
      studying mutants with altered nicotianamine levels. Mild and strong Arabidopsis
      mutants impaired in nicotianamine synthesis have been identified and
      characterized, namely nas4x-1 and nas4x-2. Arabidopsis thaliana has four NAS
      genes. In this review, we summarize the structure and evolution of the NAS genes
      in the Arabidopsis genome. We summarize previous results and present novel
      evidence that the four NAS genes have partially overlapping functions when plants
      are exposed to Fe deficiency and nickel supply. We compare the phenotypes of
      nas4x-1 and nas4x-2 and summarize the functions of NAS genes and NA as deduced
      from the studies of mutant phenotypes.

PMID- 22639606
TI  - Trehalose-6-phosphate: connecting plant metabolism and development.
AB  - Beyond their metabolic roles, sugars can also act as messengers in signal
      transduction. Trehalose, a sugar found in many species of plants and animals, is
      a non-reducing disaccharide composed of two glucose moieties. Its synthesis in
      plants is a two-step process, involving the production of trehalose-6-phosphate
      (T6P) catalyzed by trehalose-6-phosphate synthase (TPS) and its consecutive
      dephosphorylation to trehalose, catalyzed by trehalose-6-phosphate phosphatase
      (TPP). T6P has recently emerged as an important signaling metabolite, regulating
      carbon assimilation and sugar status in plants. In addition, T6P has also been
      demonstrated to play an essential role in plant development. This review
      recapitulates the recent advances we have made in understanding the role of T6P
      in coordinating diverse metabolic and developmental processes.

PMID- 22639607
TI  - Mutations in an Atypical TIR-NB-LRR-LIM Resistance Protein Confer Autoimmunity.
AB  - In order to defend against microbial infection, plants employ a complex immune
      system that relies partly on resistance (R) proteins that initiate intricate
      signaling cascades upon pathogen detection. The resistance signaling network
      utilized by plants is only partially characterized. A genetic screen conducted to
      identify novel defense regulators involved in this network resulted in the
      isolation of the snc6-1D mutant. Positional cloning revealed that this mutant
      contained a molecular lesion in the chilling sensitive 3 (CHS3) gene, thus the
      allele was renamed chs3-2D. CHS3 encodes a TIR-NB-LRR R protein that contains a C
      terminal zinc-binding LIM (Lin-11, Isl-1, Mec-3) domain. Although this protein
      has been previously implicated in cold stress and defense response, the role of
      the LIM domain in modulating protein activity is unclear. The chs3-2D allele
      contains a G to A point mutation causing a C1340 to Y1340 substitution close to
      the LIM domain. It encodes a dominant gain-of-function mutation. The chs3-2D
      mutant is severely stunted and displays curled leaf morphology. Additionally, it
      constitutively expresses PATHOGENESIS-RELATED (PR) genes, accumulates salicylic
      acid, and shows enhanced resistance to the virulent oomycete isolate
      Hyaloperonospora arabidopsidis (H.a.) Noco2. Subcellular localization assays
      using GFP fusion constructs indicate that both CHS3 and chs3-2D localize to the
      nucleus. A third chs3 mutant allele, chs3-3D, was identified in an unrelated
      genetic screen in our lab. This allele contains a C to T point mutation resulting
      in an M1017 to V1017 substitution in the LRR-LIM linker region. Additionally, a
      chs3-2D suppressor screen identified two revertant alleles containing secondary
      mutations that abolish the mutant morphology. Analysis of the locations of these
      molecular lesions provides support for the hypothesis that the LIM domain
      represses CHS3 R-like protein activity. This repression may occur through either
      autoinhibition or binding of a negative defense regulator.

PMID- 22639608
TI  - The Frustration with Utilization: Why Have Improvements in Internal Phosphorus
      Utilization Efficiency in Crops Remained so Elusive?
AB  - Despite the attention internal phosphorus utilization efficiency (PUE) of crops
      has received in the literature, little progress in breeding crop cultivars with
      high PUE has been made. Surprisingly few studies have specifically investigated
      PUE; instead, genotypic variation for PUE has been investigated in studies that
      concurrently assess phosphorus acquisition efficiency (PAE). We hypothesized that
      genotypic differences in PAE confound PUE rankings because genotypes with higher
      PAE suffer a lower degree of P stress, resulting in lower PUE. The hypothesis was
      tested by comparing soil-based screening to a modified technique whereby rice
      genotypes were grown in individual containers with a single dose of solution P,
      to eliminate differences in P uptake among genotypes. Genotypic differences in
      PUE were apparent in root and shoot tissue using the modified nutrient solution
      technique, but PUE rankings showed no correlation with those from traditional
      soil-based screening. We conclude that PUE in soil-based screening systems is
      unavoidably linked with genotypic PAE, resulting in PUE rankings confounded by
      differences in P uptake. Only screening techniques assuring equal P uptake are
      suitable for the exploitation of genotypic variation for PUE.

PMID- 22639610
TI  - Transcriptional plant responses critical for resistance towards necrotrophic
      pathogens.
AB  - Plant defenses aimed at necrotrophic pathogens appear to be genetically complex.
      Despite the apparent lack of a specific recognition of such necrotrophs by
      products of major R genes, biochemical, molecular, and genetic studies, in
      particular using the model plant Arabidopsis, have uncovered numerous host
      components critical for the outcome of such interactions. Although the JA
      signaling pathway plays a central role in plant defense toward necrotrophs
      additional signaling pathways contribute to the plant response network.
      Transcriptional reprogramming is a vital part of the host defense machinery and
      several key regulators have recently been identified. Some of these transcription
      factors positively affect plant resistance whereas others play a role in
      enhancing host susceptibility toward these phytopathogens.

PMID- 22639609
TI  - Insights into auxin signaling in plant-pathogen interactions.
AB  - The phytohormone auxin has been known to be a regulator of plant growth and
      development ever since its discovery. Recent studies on plant-pathogen
      interactions identify auxin as a key character in pathogenesis and plant defense.
      Like plants, diverse pathogens possess the capacity to synthesize indole-3-acetic
      acid (IAA), the major form of auxin in plants. The emerging knowledge on auxin
      signaling components, auxin metabolic processes, and indole-derived phytoalexins
      in plant responses to pathogen invasion has provided putative mechanisms of IAA
      in plant susceptibility and resistance to non-gall- or tumor-inducing pathogens.

PMID- 22639611
TI  - Editorial overview - computational approaches in aid of advancing understanding
      in plant physiology.

PMID- 22639612
TI  - In the Light of Evolution: A Reevaluation of Conservation in the CO-FT Regulon
      and Its Role in Photoperiodic Regulation of Flowering Time.
AB  - In order to maximize reproductive success, plants have evolved different
      strategies to control the critical developmental shift marked by the transition
      to flowering. As plants have adapted to diverse environments across the globe,
      these strategies have evolved to recognize and respond to local seasonal cues
      through the induction of specific downstream genetic pathways, thereby ensuring
      that the floral transition occurs in favorable conditions. Determining the
      genetic factors involved in controlling the floral transition in many species is
      key to understanding how this trait has evolved. Striking genetic discoveries in
      Arabidopsis thaliana (Arabidopsis) and Oryza sativa (rice) revealed that similar
      genes in both species control flowering in response to photoperiod, suggesting
      that this genetic module could be conserved between distantly related
      angiosperms. However, as we have gained a better understanding of the complex
      evolution of these genes and their functions in other species, another
      possibility must be considered: that the genetic module controlling flowering in
      response to photoperiod is the result of convergence rather than conservation. In
      this review, we show that while data clearly support a central role of FLOWERING
      LOCUS T (FT) homologs in floral promotion across a diverse group of angiosperms,
      there is little evidence for a conserved role of CONSTANS (CO) homologs in the
      regulation of these loci. In addition, although there is an element of conserved
      function for FT homologs, even this component has surprising complexity in its
      regulation and evolution.

PMID- 22639613
TI  - Detecting functional groups of Arabidopsis mutants by metabolic profiling and
      evaluation of pleiotropic responses.
AB  - Metabolic profiles and fingerprints of Arabidopsis thaliana plants with various
      defects in plastidic sugar metabolism or photosynthesis were analyzed to
      elucidate if the genetic mutations can be traced by comparing their metabolic
      status. Using a platform of chromatographic and spectrometric tools data from
      untargeted full MS scans as well as from selected metabolites including major
      carbohydrates, phosphorylated intermediates, carboxylates, free amino acids,
      major antioxidants, and plastidic pigments were evaluated. Our key observations
      are that by multivariate statistical analysis each mutant can be separated by a
      unique metabolic signature. Closely related mutants come close. Thus metabolic
      profiles of sugar mutants are different but more similar than those of
      photosynthesis mutants. All mutants show pleiotropic responses mirrored in their
      metabolic status. These pleiotropic responses are typical and can be used for
      separating and grouping of the mutants. Our findings show that metabolite
      fingerprints can be taken to classify mutants and hence may be used to sort genes
      into functional groups.

PMID- 22639614
TI  - Mining Functional Elements in Messenger RNAs: Overview, Challenges, and
      Perspectives.
AB  - Eukaryotic messenger RNA (mRNA) contains not only protein-coding regions but also
      a plethora of functional cis-elements that influence or coordinate a number of
      regulatory aspects of gene expression, such as mRNA stability, splicing forms,
      and translation rates. Understanding the rules that apply to each of these
      element types (e.g., whether the element is defined by primary or higher-order
      structure) allows for the discovery of novel mechanisms of gene expression as
      well as the design of transcripts with controlled expression. Bioinformatics
      plays a major role in creating databases and finding non-evident patterns
      governing each type of eukaryotic functional element. Much of what we currently
      know about mRNA regulatory elements in eukaryotes is derived from microorganism
      and animal systems, with the particularities of plant systems lagging behind. In
      this review, we provide a general introduction to the most well-known eukaryotic
      mRNA regulatory motifs (splicing regulatory elements, internal ribosome entry
      sites, iron-responsive elements, AU-rich elements, zipcodes, and polyadenylation
      signals) and describe available bioinformatics resources (databases and analysis
      tools) to analyze eukaryotic transcripts in search of functional elements,
      focusing on recent trends in bioinformatics methods and tool development. We also
      discuss future directions in the development of better computational tools based
      upon current knowledge of these functional elements. Improved computational tools
      would advance our understanding of the processes underlying gene regulations. We
      encourage plant bioinformaticians to turn their attention to this subject to help
      identify novel mechanisms of gene expression regulation using RNA motifs that
      have potentially evolved or diverged in plant species.

PMID- 22639616
TI  - Mining the Active Proteome of Arabidopsis thaliana.
AB  - Assigning functions to the >30,000 proteins encoded by the Arabidopsis genome is
      a challenging task of the Arabidopsis Functional Genomics Network. Although
      genome-wide technologies like proteomics and transcriptomics have generated a
      wealth of information that significantly accelerated gene annotation, protein
      activities are poorly predicted by transcript or protein levels as protein
      activities are post-translationally regulated. To directly display protein
      activities in Arabidopsis proteomes, we developed and applied activity-based
      protein profiling (ABPP). ABPP is based on the use of small molecule probes that
      react with the catalytic residues of distinct protein classes in an activity
      dependent manner. Labeled proteins are separated and detected from proteins gels
      and purified and identified by mass spectrometry. Using probes of six different
      chemotypes we have displayed activities of 76 Arabidopsis proteins. These
      proteins represent over 10 different protein classes that contain over 250
      Arabidopsis proteins, including cysteine, serine, and metalloproteases, lipases,
      acyltransferases, and the proteasome. We have developed methods for
      identification of in vivo labeled proteins using click chemistry and for in vivo
      imaging with fluorescent probes. In vivo labeling has revealed additional protein
      activities and unexpected subcellular activities of the proteasome. Labeling of
      extracts displayed several differential activities, e.g., of the proteasome
      during immune response and methylesterases during infection. These studies
      illustrate the power of ABPP to display the functional proteome and testify to a
      successful interdisciplinary collaboration involving chemical biology, organic
      chemistry, and proteomics.

PMID- 22639617
TI  - Transgenerational adaptation to heavy metal salts in Arabidopsis.
AB  - Exposure to abiotic and biotic stress results in changes in plant physiology and
      triggers genomic instability. Recent reports suggest that the progeny of stressed
      plants also exhibit changes in genome stability, stress tolerance, and
      methylation. Here we analyzed whether exposure to Ni(2+), Cd(2+), and Cu(2+)
      salts leads to transgenerational changes in homologous recombination frequency
      and stress tolerance. We found that the immediate progeny of stressed plants
      exhibited an increased rate of recombination. However, when the progeny of
      stressed plants was propagated without stress, recombination reverted to normal
      levels. Exposure of plants to heavy metals for five consecutive generations (S1
      S5) resulted in recombination frequency being maintained at a high level.
      Skipping stress following two to three generations of propagation with 50 mM
      Ni(2+) or Cd(2+) did not decrease the recombination frequency, suggesting plant
      acclimation to upregulated recombination. Analysis of the progeny of plants
      exposed to Cu(2+) and Ni(2+) indicated higher stress tolerance to the heavy metal
      parental plants were exposed to. Tolerance was higher in plants propagated with
      stress for three to five generations, which resulted in longer roots than plants
      propagated on heavy metals for only one to two generations. Tolerance was also
      more prominent upon exposure to a higher concentration of salts. The progeny of
      stressed plants were also more tolerant to NaCl and methyl methane sulfonate.

PMID- 22639615
TI  - Calcium efflux systems in stress signaling and adaptation in plants.
AB  - Transient cytosolic calcium ([Ca(2+)](cyt)) elevation is an ubiquitous
      denominator of the signaling network when plants are exposed to literally every
      known abiotic and biotic stress. These stress-induced [Ca(2+)](cyt) elevations
      vary in magnitude, frequency, and shape, depending on the severity of the stress
      as well the type of stress experienced. This creates a unique stress-specific
      calcium "signature" that is then decoded by signal transduction networks. While
      most published papers have been focused predominantly on the role of Ca(2+)
      influx mechanisms to shaping [Ca(2+)](cyt) signatures, restoration of the basal
      [Ca(2+)](cyt) levels is impossible without both cytosolic Ca(2+) buffering and
      efficient Ca(2+) efflux mechanisms removing excess Ca(2+) from cytosol, to reload
      Ca(2+) stores and to terminate Ca(2+) signaling. This is the topic of the current
      review. The molecular identity of two major types of Ca(2+) efflux systems,
      Ca(2+)-ATPase pumps and Ca(2+)/H(+) exchangers, is described, and their
      regulatory modes are analyzed in detail. The spatial and temporal organization of
      calcium signaling networks is described, and the importance of existence of
      intracellular calcium microdomains is discussed. Experimental evidence for the
      role of Ca(2+) efflux systems in plant responses to a range of abiotic and biotic
      factors is summarized. Contribution of Ca(2+)-ATPase pumps and Ca(2+)/H(+)
      exchangers in shaping [Ca(2+)](cyt) signatures is then modeled by using a four
      component model (plasma- and endo-membrane-based Ca(2+)-permeable channels and
      efflux systems) taking into account the cytosolic Ca(2+) buffering. It is
      concluded that physiologically relevant variations in the activity of Ca(2+)
      ATPase pumps and Ca(2+)/H(+) exchangers are sufficient to fully describe all the
      reported experimental evidence and determine the shape of [Ca(2+)](cyt)
      signatures in response to environmental stimuli, emphasizing the crucial role
      these active efflux systems play in plant adaptive responses to environment.

PMID- 22639618
TI  - Embryonic development in Arabidopsis thaliana: from the zygote division to the
      shoot meristem.
AB  - Postembryonic organ formation of plants is fueled with cells from the stem cell
      niches in the shoot and root meristems. During the last two decades many players
      that regulate stem cell maintenance have been identified. With these factors in
      hand, the mechanisms establishing stem cell niches during embryo development can
      be addressed. Here we discuss current models of how the shoot meristem stem cell
      niche arises during Arabidopsis embryo pattern formation.

PMID- 22639619
TI  - The Alphabet of Galactolipids in Arabidopsis thaliana.
AB  - Galactolipids constitute the major lipid class in plants. In recent years
      oxygenated derivatives of galactolipids have been detected. They are discussed as
      signal molecules during leaf damage, since they accumulate in wounded leaves in
      high levels. Using different analytical methods such as nuclear magnetic
      resonance, infra-red spectroscopy, and high performance liquid
      chromatography/mass spectrometry (HPLC/MS) earlier reports focused on the
      analysis of either oxidized or non-oxidized species and needed high levels of
      analytes. Here, we report on the analysis of the galactolipid subfraction of the
      Arabidopsis leaf lipidome by an improved HPLC/MS(2)-based method that is fast,
      robust, and comparatively simple in its performance. Due to a combination of
      phase partitioning, solid phase fractionation, liquid chromatography, and MS(2)
      experiments this method has high detection sensitivity and requires only low
      amounts of plant material. With this method 167 galactolipid species were
      detected in leaves of Arabidopsis thaliana. Out of these 79 being newly described
      species. From all species the head group and acyl side chains were identified via
      MS(2) experiments. Moreover, the structural identification was supported by
      HPLC/time-of-flight (TOF)-MS and gas chromatography (GC)/MS analysis. The
      quantification of different galactolipid species that accumulated 30 min after a
      mechanical wounding in A. thaliana leaves showed that the oxidized acyl side
      chains in galactolipids are divided into 65% cyclopentenones, 27% methyl-branched
      ketols, 3.8% hydroperoxides/straight-chain ketols, 2.0% hydroxides, and 2.6%
      phytoprostanes. In comparison to the free cyclopentenone derivatives, the
      esterified forms occur in a 149-fold excess supporting the hypothesis that
      galactolipids might function as storage compounds for cyclopentenones. Additional
      analysis of the ratio of non-oxidized to oxidized galactolipid species in leaves
      of wounded plants was performed resulting in a ratio of 2.0 in case of
      monogalactosyl diacylglycerol (MGD), 8.1 in digalactosyl diacylglycerol (DGD),
      and 0.6 in the acylated MGD. This indicates that galactolipid oxidation is a
      major and rapid metabolic process that occurs class specific.

PMID- 22639620
TI  - Arabidopsis 14-3-3 proteins: fascinating and less fascinating aspects.
AB  - 14-3-3 Dimers are well known to interact with diverse target proteins throughout
      eukaryotes. Most notably, association of 14-3-3s commonly requires
      phosphorylation of a serine or threonine residue within a specific sequence motif
      of the client protein. Studies with a focus on individual target proteins have
      unequivocally demonstrated 14-3-3s to be the crucial factors modifying the
      client's activity state upon phosphorylation and, thus, finishing the job
      initiated by a kinase. In this respect, a recent in-depth analysis of the rice
      transcription factor FLOWERING LOCUS D1 (OsFD1) revealed 14-3-3s to be essential
      players in floral induction. Such fascinating discoveries, however, can often be
      ascribed to the random identification of 14-3-3 as an interaction partner of the
      favorite protein. In contrast, our understanding of 14-3-3 function in higher
      organisms is frustratingly limited, mainly due to an overwhelming spectrum of
      putative targets in combination with the existence of a multigene 14-3-3 family.
      In this review we will discuss our current understanding of the function of plant
      14-3-3 proteins, taking into account recent surveys of the Arabidopsis 14-3-3
      interactome.

PMID- 22639621
TI  - RNA decay and RNA silencing in plants: competition or collaboration?
AB  - Initiation of RNA polymerase II transcription signals the beginning of a series
      of physically and functionally coupled pre-mRNA processing events that transform
      an RNA transcript into a highly structured, mature ribonucleoprotein complex.
      With such a complexity of co-transcriptional processes comes the need to identify
      and degrade improperly processed transcripts. Quality control of mRNA expression
      primarily involves exonucleolytic degradation of aberrant RNAs. RNA silencing, on
      the other hand, tends to be viewed separately as a pathway that primarily
      functions in regulating endogenous gene expression and in genome defense against
      transposons and viruses. Here, we review current knowledge of these pathways as
      they exist in plants and draw parallels to similar pathways in other eukaryotes.
      We then highlight some unexplored overlaps that exist between the RNA silencing
      and RNA decay pathways of plants, as evidenced by their shared RNA substrates and
      shared genetic requirements.

PMID- 22639622
TI  - The microbe-free plant: fact or artifact?
AB  - Plant-microbe interactions are ubiquitous. Plants are threatened by pathogens,
      but they are even more commonly engaged in neutral or mutualistic interactions
      with microbes: belowground microbial plant associates are mycorrhizal fungi,
      Rhizobia, and plant-growth promoting rhizosphere bacteria, aboveground plant
      parts are colonized by internally living bacteria and fungi (endophytes) and by
      microbes in the phyllosphere (epiphytes). We emphasize here that a completely
      microbe-free plant is an exotic exception rather than the biologically relevant
      rule. The complex interplay of such microbial communities with the host-plant
      affects multiple vital parameters such as plant nutrition, growth rate,
      resistance to biotic and abiotic stressors, and plant survival and distribution.
      The mechanisms involved reach from direct ones such as nutrient acquisition, the
      production of plant hormones, or direct antibiosis, to indirect ones that are
      mediated by effects on host resistance genes or via interactions at higher
      trophic levels. Plant-associated microbes are heterotrophic and cause costs to
      their host plant, whereas the benefits depend on the current environment. Thus,
      the outcome of the interaction for the plant host is highly context dependent. We
      argue that considering the microbe-free plant as the "normal" or control stage
      significantly impairs research into important phenomena such as (1) phenotypic
      and epigenetic plasticity, (2) the "normal" ecological outcome of a given
      interaction, and (3) the evolution of plants. For the future, we suggest
      cultivation-independent screening methods using direct PCR from plant tissue of
      more than one fungal and bacterial gene to collect data on the true microbial
      diversity in wild plants. The patterns found could be correlated to host species
      and environmental conditions, in order to formulate testable hypotheses on the
      biological roles of plant endophytes in nature. Experimental approaches should
      compare different host-endophyte combinations under various relevant
      environmental conditions and study at the genetic, epigenetic, transcriptional,
      and physiological level the parameters that cause the interaction to shift along
      the mutualism-parasitism continuum.

PMID- 22639623
TI  - The yeast three-hybrid system as an experimental platform to identify proteins
      interacting with small signaling molecules in plant cells: potential and
      limitations.
AB  - Chemical genetics is a powerful scientific strategy that utilizes small bioactive
      molecules as experimental tools to unravel biological processes. Bioactive
      compounds occurring in nature represent an enormous diversity of structures that
      can be used to dissect functions of biological systems. Once the bioactivity of a
      natural or synthetic compound has been critically evaluated the challenge remains
      to identify its molecular target and mode of action, which usually is a time
      consuming and labor-intensive process. To facilitate this task, we decided to
      implement the yeast three-hybrid (Y3H) technology as a general experimental
      platform to scan the whole Arabidopsis proteome for targets of small signaling
      molecules. The Y3H technology is based on the yeast two-hybrid system and allows
      direct cloning of proteins that interact in vivo with a synthetic hybrid ligand,
      which comprises the biologically active molecule of interest covalently linked to
      methotrexate (Mtx). In yeast nucleus the hybrid ligand connects two fusion
      proteins: the Mtx part binding to dihydrofolate reductase fused to a DNA-binding
      domain (encoded in the yeast strain), and the bioactive molecule part binding to
      its potential protein target fused to a DNA-activating domain (encoded on a cDNA
      expression vector). During cDNA library screening, the formation of this ternary,
      transcriptional activator complex leads to reporter gene activation in yeast
      cells, and thereby allows selection of the putative targets of small bioactive
      molecules of interest. Here we present the strategy and experimental details for
      construction and application of a Y3H platform, including chemical synthesis of
      different hybrid ligands, construction of suitable cDNA libraries, the choice of
      yeast strains, and appropriate screening conditions. Based on the results
      obtained and the current literature we discuss the perspectives and limitations
      of the Y3H approach for identifying targets of small bioactive molecules.

PMID- 22639624
TI  - Adaptive transgenerational plasticity in plants: case studies, mechanisms, and
      implications for natural populations.
AB  - Plants respond to environmental conditions not only by plastic changes to their
      own development and physiology, but also by altering the phenotypes expressed by
      their offspring. This transgenerational plasticity was initially considered to
      entail only negative effects of stressful parental environments, such as
      production of smaller seeds by resource- or temperature-stressed parent plants,
      and was therefore viewed as environmental noise. Recent evolutionary ecology
      studies have shown that in some cases, these inherited environmental effects can
      include specific growth adjustments that are functionally adaptive to the
      parental conditions that induced them, which can range from contrasting states of
      controlled laboratory environments to the complex habitat variation encountered
      by natural plant populations. Preliminary findings suggest that adaptive
      transgenerational effects can be transmitted by means of diverse mechanisms
      including changes to seed provisioning and biochemistry, and epigenetic
      modifications such as DNA methylation that can persist across multiple
      generations. These non-genetically inherited adaptations can influence the
      ecological breadth and evolutionary dynamics of plant taxa and promote the spread
      of invasive plants. Interdisciplinary studies that join mechanistic and
      evolutionary ecology approaches will be an important source of future insights.

PMID- 22639626
TI  - Effect of Pre-Harvest Foliar Application of Citric Acid and Malic Acid on
      Chlorophyll Content and Post-Harvest Vase Life of Lilium cv. Brunello.
AB  - Citric acid is a regular ingredient in many vase solution formulations but pre
      harvest use of citric acid is a novel method in vase life extension of cut
      flowers, which is reported on tuberose earlier. In order to verify previous
      result, and check for possible substitution of citric acid by malic acid, the
      current research was designed. Citric acid (0, 0.075, 0.15% w/v) and malic acid
      (0, 0.075, 0.15% w/v) were used in a factorial design with three replications.
      Foliar sprays were applied two times during growth period of Lilium plants. The
      results point out that 0.15% citric acid alone had increased vase life from 11.8
      in control treatment to 14 days (alpha < 0.05). The interesting finding was the
      effect of citric acid on bulbil weight, which was decreased from 9 g in control
      to 1.5 g in treatment containing combination of 0.075% citric acid and 0.075%
      malic acid. Malic acid while having no direct effect on pre-mentioned traits
      surprisingly increased the chlorophyll content significantly. The interaction
      effect between citric acid and malic acid on vase life and chlorophyll content
      proved significant and was evident in results, both as antagonistic and
      synergistic in various traits.

PMID- 22639625
TI  - A plethora of virulence strategies hidden behind nuclear targeting of microbial
      effectors.
AB  - Plant immune responses depend on the ability to couple rapid recognition of the
      invading microbe to an efficient response. During evolution, plant pathogens have
      acquired the ability to deliver effector molecules inside host cells in order to
      manipulate cellular and molecular processes and establish pathogenicity.
      Following translocation into plant cells, microbial effectors may be addressed to
      different subcellular compartments. Intriguingly, a significant number of
      effector proteins from different pathogenic microorganisms, including viruses,
      oomycetes, fungi, nematodes, and bacteria, is targeted to the nucleus of host
      cells. In agreement with this observation, increasing evidence highlights the
      crucial role played by nuclear dynamics, and nucleocytoplasmic protein
      trafficking during a great variety of analyzed plant-pathogen interactions. Once
      in the nucleus, effector proteins are able to manipulate host transcription or
      directly subvert essential host components to promote virulence. Along these
      lines, it has been suggested that some effectors may affect histone packing and,
      thereby, chromatin configuration. In addition, microbial effectors may either
      directly activate transcription or target host transcription factors to alter
      their regular molecular functions. Alternatively, nuclear translocation of
      effectors may affect subcellular localization of their cognate resistance
      proteins in a process that is essential for resistance protein-mediated plant
      immunity. Here, we review recent progress in our field on the identification of
      microbial effectors that are targeted to the nucleus of host plant cells. In
      addition, we discuss different virulence strategies deployed by microbes, which
      have been uncovered through examination of the mechanisms that guide nuclear
      localization of effector proteins.

PMID- 22639627
TI  - Plant Lessons: Exploring ABCB Functionality Through Structural Modeling.
AB  - In contrast to mammalian ABCB1 proteins, narrow substrate specificity has been
      extensively documented for plant orthologs shown to catalyze the transport of the
      plant hormone, auxin. Using the crystal structures of the multidrug exporters
      Sav1866 and MmABCB1 as templates, we have developed structural models of plant
      ABCB proteins with a common architecture. Comparisons of these structures
      identified kingdom-specific candidate substrate-binding regions within the
      translocation chamber formed by the transmembrane domains of ABCBs from the model
      plant Arabidopsis. These results suggest an early evolutionary divergence of
      plant and mammalian ABCBs. Validation of these models becomes a priority for
      efforts to elucidate ABCB function and manipulate this class of transporters to
      enhance plant productivity and quality.

PMID- 22639628
TI  - AGO2: A New Argonaute Compromising Plant Virus Accumulation.
AB  - Plant viruses use several strategies to transport their nucleic acid genomes
      throughout the plants. Regardless of the movement mechanism, a universal major
      block to uninterrupted viral trafficking is the induction of antiviral silencing
      that degrades viral RNA. To counteract this defense, viruses encode suppressors
      that block certain steps in the RNA silencing pathway, and consequently these
      proteins allow viral spread to proceed. There is a constant battle between plants
      and viruses and sometimes viruses will succeed and invade the plants and in other
      cases the RNA silencing mechanism will override the virus. A key role in the
      silencing versus suppression conflict between plants and viruses is played by one
      or more members of the Argonaute protein (AGO) family encoded by plants. Here we
      review the mechanisms and effects of antiviral silencing with an emphasis on the
      contribution of AGOs, especially the recently discovered role of AGO2.

PMID- 22639629
TI  - Variable Regions of PI4P 5-Kinases Direct PtdIns(4,5)P(2) Toward Alternative
      Regulatory Functions in Tobacco Pollen Tubes.
AB  - The apical plasma membrane of pollen tubes contains different PI4P 5-kinases that
      all produce phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P(2)] but exert
      distinct cellular effects. In the present example, overexpression of Arabidopsis
      AtPIP5K5 or tobacco NtPIP5K6-1 caused growth defects previously attributed to
      increased pectin secretion. In contrast, overexpression of Arabidopsis AtPIP5K2
      caused apical tip swelling implicated in altering actin fine structure in the
      pollen tube apex. AtPIP5K5, NtPIP5K6-1, and AtPIP5K2 share identical domain
      structures. Domains required for correct membrane association of the enzymes were
      identified by systematic deletion of N-terminal domains and subsequent expression
      of fluorescence-tagged enzyme truncations in tobacco pollen tubes. A variable
      linker region (Lin) contained in all PI4P 5-kinase isoforms of subfamily B, but
      not conserved in sequence, was recognized to be necessary for correct subcellular
      localization of AtPIP5K5, NtPIP5K6-1, and AtPIP5K2. Deletion of N-terminal
      domains including the Lin domain did not impair catalytic activity of recombinant
      AtPIP5K5, NtPIP5K6-1, or AtPIP5K2 in vitro; however, the presence of the Lin
      domain was necessary for in vivo effects on pollen tube growth upon
      overexpression of truncated enzymes. Overexpression of catalytically inactive
      variants of AtPIP5K5, NtPIP5K6-1, or AtPIP5K2 did not influence pollen tube
      growth, indicating that PtdIns(4,5)P(2) production rather than structural
      properties of PI4P 5-kinases was relevant for the manifestation of growth
      phenotypes. When Lin domains were swapped between NtPIP5K6-1 and AtPIP5K2 and the
      chimeric enzymes overexpressed in pollen tubes, the chimeras reciprocally gained
      the capabilities to invoke tip swelling or secretion phenotypes, respectively.
      The data indicate that the Lin domain directed the enzymes into different
      regulatory contexts, possibly contributing to channeling of PtdIns(4,5)P(2) at
      the interface of secretion and actin cytoskeleton.

PMID- 22639630
TI  - Pleiotropic roles of cold shock domain proteins in plants.
AB  - The cold shock domain (CSD) is a nucleic acid binding domain that is widely
      conserved from bacteria to higher plants and animals. In Escherichia coli, cold
      shock proteins (CSPs) are composed solely of a CSD and function as RNA chaperones
      that destabilize RNA secondary structures. Cellular RNAs tend to be folded into
      unfavorable structures under low temperature conditions, and RNA chaperones
      resolve these structures, recovering functionality of the RNAs. CSP functions are
      associated mainly with cold adaptation, but they are also involved in other
      biological processes under normal growth conditions. Eukaryotic CSD proteins
      contain auxiliary domains in addition to the CSD and regulate many biological
      processes such as development and stress tolerance. In plants, it has been
      demonstrated that CSD proteins play essential roles in acquiring freezing
      tolerance. In addition, it has been suggested that some plant CSD proteins
      regulate embryo development, flowering time, and fruit development. In this
      review, we summarize the pleiotropic biological functions of CSP proteins in
      plants and discuss possible mechanisms by which plant CSD proteins regulate the
      functions of RNA molecules.

PMID- 22639631
TI  - Protein-induced modulation of chloroplast membrane morphology.
AB  - Organelles are surrounded by membranes with a distinct lipid and protein
      composition. While it is well established that lipids affect protein functioning
      and vice versa, it has been only recently suggested that elevated membrane
      protein concentrations may affect the shape and organization of membranes. We
      therefore analyzed the effects of high chloroplast envelope protein
      concentrations on membrane structures using an in vivo approach with protoplasts.
      Transient expression of outer envelope proteins or protein domains such as CHUP1
      TM-GFP, outer envelope protein of 7 kDa-GFP, or outer envelope protein of 24 kDa
      GFP at high levels led to the formation of punctate, circular, and tubular
      membrane protrusions. Expression of inner membrane proteins such as translocase
      of inner chloroplast membrane 20, isoform II (Tic20-II)-GFP led to membrane
      protrusions including invaginations. Using increasing amounts of DNA for
      transfection, we could show that the frequency, size, and intensity of these
      protrusions increased with protein concentration. The membrane deformations were
      absent after cycloheximide treatment. Co-expression of CHUP1-TM-Cherry and Tic20
      II-GFP led to membrane protrusions of various shapes and sizes including some
      stromule-like structures, for which several functions have been proposed.
      Interestingly, some structures seemed to contain both proteins, while others seem
      to contain one protein exclusively, indicating that outer and inner envelope
      dynamics might be regulated independently. While it was more difficult to
      investigate the effects of high expression levels of membrane proteins on
      mitochondrial membrane shapes using confocal imaging, it was striking that the
      expression of the outer membrane protein Tom20 led to more elongate mitochondria.
      We discuss that the effect of protein concentrations on membrane structure is
      possibly caused by an imbalance in the lipid to protein ratio and may be involved
      in a signaling pathway regulating membrane biogenesis. Finally, the observed
      phenomenon provides a valuable experimental approach to investigate the
      relationship between lipid synthesis and membrane protein expression in future
      studies.

PMID- 22639633
TI  - Suberin goes genomics: use of a short living plant to investigate a long lasting
      polymer.
AB  - Suberin is a highly persistent cell wall polymer, predominantly composed of long
      chain hydroxylated fatty acids. Apoplastic suberin depositions occur in internal
      and peripheral dermal tissues where they generate lipophilic barriers preventing
      uncontrolled flow of water, gases, and ions. In addition, suberization provides
      resistance to environmental stress conditions. Despite this physiological
      importance the knowledge about suberin formation has increased slowly for
      decades. Lately, the chemical characterization of suberin in Arabidopsis enabled
      the proposal of genes required for suberin biosynthesis such as beta-ketoacyl-CoA
      synthases (KCS) for fatty acid elongation and cytochrome P450 oxygenases (CYP)
      for fatty acid hydroxylation. Advantaged by the Arabidopsis molecular genetic
      resources the in silico expression pattern of candidate genes, concerted with the
      tissue-specific distribution of suberin in Arabidopsis, led to the identification
      of suberin involved genes including KCS2, CYP86A1, and CYP86B1. The isolation of
      mutants with a modified suberin composition facilitated physiological studies
      revealing that the strong reduction in suberin in cyp86a1 mutants results in
      increased root water and solute permeabilities. The enhanced suberin 1 mutant,
      characterized by twofold increased root suberin content, has increased water-use
      efficiency and is affected in mineral ion uptake and transport. In this review
      the most recent findings on the biosynthesis and physiological importance of
      suberin in Arabidopsis are summarized and discussed.

PMID- 22639632
TI  - The plant mitochondrial carrier family: functional and evolutionary aspects.
AB  - Mitochondria play a key role in respiration and energy production and are
      involved in multiple eukaryotic but also in several plant specific metabolic
      pathways. Solute carriers in the inner mitochondrial membrane connect the
      internal metabolism with that of the surrounding cell. Because of their common
      basic structure, these transport proteins affiliate to the mitochondrial carrier
      family (MCF). Generally, MCF proteins consist of six membrane spanning helices,
      exhibit typical conserved domains and appear as homodimers in the native
      membrane. Although structurally related, MCF proteins catalyze the specific
      transport of various substrates, such as nucleotides, amino acids,
      dicarboxylates, cofactors, phosphate or H(+). Recent investigations identified
      MCF proteins also in several other cellular compartments and therefore their
      localization and physiological function is not only restricted to mitochondria.
      MCF proteins are a characteristic feature of eukaryotes and bacterial genomes
      lack corresponding sequences. Therefore, the evolutionary origin of MCF proteins
      is most likely associated with the establishment of mitochondria. It is not clear
      whether the host cell, the symbiont, or the chimerical organism invented the
      ancient MCF sequence. Here, we try to explain the establishment of different MCF
      proteins and focus on the characteristics of members from plants, in particular
      from Arabidopsis thaliana.

PMID- 22639634
TI  - TCUP: A Novel hAT Transposon Active in Maize Tissue Culture.
AB  - Transposable elements (TEs) are capable of inducing heritable de novo genetic
      variation. The sequences capable of reactivation, and environmental factors that
      induce mobilization, remain poorly defined even in well-studied genomes such as
      maize. We treated maize tissue culture with the demethylating agent 5-aza-2
      deoxcytidine and examined long-term tissue culture lines to discover silenced TEs
      that have the potential to induce heritable genetic variation. Through these
      screens we have identified a novel low copy number hAT transposon, Tissue Culture
      Up-Regulated (TCUP), which is transcribed at high levels in long-term maize black
      Mexican sweet (BMS) tissue culture and is transcribed in response to treatment
      with 5-aza-2-deoxycytidine. Analysis of the TIGR Maize Gene Index revealed that
      this element is the most frequently represented EST from the BMS cell culture
      library and is not represented in other tissue libraries, which is the basis for
      its name. A full-length sequence was assembled in inbred B73 that contains the
      putative functional motifs required for autonomous movement of a hAT transposon.
      Transposon display detected novel TCUP insertions in two long-term tissue
      cultured cell lines of the genotype Hi-II A * B and BMS. This research implicates
      TCUP as a transposon that is capable of reactivation and which may also be
      particularly sensitive to the stress of the tissue culture environment. Our
      findings are consistent with the hypothesis that epigenetic alterations
      potentiate genomic responses to stress during clonal propagation of plants.

PMID- 22639637
TI  - Manipulation of plant host susceptibility: an emerging role for viral movement
      proteins?
AB  - Viruses encode viral suppressors of RNA silencing (VSRs) to counteract RNA
      silencing, a major antiviral defense response in plants. Recent studies indicate
      a role of virus-derived siRNAs in manipulating the expression of specific host
      genes and that certain plant viral movement proteins (MPs) can act as viral
      enhancers of RNA silencing (VERs) by stimulating the spread of silencing between
      cells. This suggests that viruses have evolved complex responses capable to
      efficiently hijack the host RNA silencing machinery to their own advantage. We
      draw here a dynamic model of the interaction of plant viruses with the silencing
      machinery during invasion of the host. The model proposes that cells at the
      spreading front of infection, where infection starts from zero and the VSR levels
      are supposedly low, represent potential sites for viral manipulation of host gene
      expression by using virus- and host-derived small RNAs. Viral MPs may facilitate
      the spread of silencing to produce a wave of small RNA-mediated gene expression
      changes ahead of the infection to increase host susceptibility. When
      experimentally ascertained, this hypothetical model will call for re-defining
      viral movement and the function of viral MPs.

PMID- 22639636
TI  - The spliceosome-activating complex: molecular mechanisms underlying the function
      of a pleiotropic regulator.
AB  - Correct interpretation of the coding capacity of RNA polymerase II transcribed
      eukaryotic genes is determined by the recognition and removal of intronic
      sequences of pre-mRNAs by the spliceosome. Our current knowledge on dynamic
      assembly and subunit interactions of the spliceosome mostly derived from the
      characterization of yeast, Drosophila, and human spliceosomal complexes formed on
      model pre-mRNA templates in cell extracts. In addition to sequential structural
      rearrangements catalyzed by ATP-dependent DExH/D-box RNA helicases, catalytic
      activation of the spliceosome is critically dependent on its association with the
      NineTeen Complex (NTC) named after its core E3 ubiquitin ligase subunit PRP19.
      NTC, isolated recently from Arabidopsis, occurs in a complex with the essential
      RNA helicase and GTPase subunits of the U5 small nuclear RNA particle that are
      required for both transesterification reactions of splicing. A compilation of
      mass spectrometry data available on the composition of NTC and spliceosome
      complexes purified from different organisms indicates that about half of their
      conserved homologs are encoded by duplicated genes in Arabidopsis. Thus, while
      mutations of single genes encoding essential spliceosome and NTC components lead
      to cell death in other organisms, differential regulation of some of their
      functionally redundant Arabidopsis homologs permits the isolation of partial loss
      of function mutations. Non-lethal pleiotropic defects of these mutations provide
      a unique means for studying the roles of NTC in co-transcriptional assembly of
      the spliceosome and its crosstalk with DNA repair and cell death signaling
      pathways.

PMID- 22639638
TI  - O-acetylation of plant cell wall polysaccharides.
AB  - Plant cell walls are composed of structurally diverse polymers, many of which are
      O-acetylated. How plants O-acetylate wall polymers and what its function is
      remained elusive until recently, when two protein families were identified in the
      model plant Arabidopsis that are involved in the O-acetylation of wall
      polysaccharides - the reduced wall acetylation (RWA) and the trichome
      birefringence-like (TBL) proteins. This review discusses the role of these two
      protein families in polysaccharide O-acetylation and outlines the differences and
      similarities of polymer acetylation mechanisms in plants, fungi, bacteria, and
      mammals. Members of the TBL protein family had been shown to impact pathogen
      resistance, freezing tolerance, and cellulose biosynthesis. The connection of
      TBLs to polysaccharide O-acetylation thus gives crucial leads into the biological
      function of wall polymer O-acetylation. From a biotechnological point
      understanding the O-acetylation mechanism is important as acetyl-substituents
      inhibit the enzymatic degradation of wall polymers and released acetate can be a
      potent inhibitor in microbial fermentations, thus impacting the economic
      viability of, e.g., lignocellulosic based biofuel production.

PMID- 22639635
TI  - Gene regulation by cytokinin in Arabidopsis.
AB  - The plant hormone cytokinin realizes at least part of its signaling output
      through the regulation of gene expression. A great part of the early
      transcriptional regulation is mediated by type-B response regulators, which are
      transcription factors of the MYB family. Other transcription factors, such as the
      cytokinin response factors of the AP2/ERF family, have also been shown to be
      involved in this process. Additional transcription factors mediate distinct parts
      of the cytokinin response through tissue- and cell-specific downstream
      transcriptional cascades. In Arabidopsis, only a single cytokinin response
      element, to which type-B response regulators bind, has been clearly proven so
      far, which has 5'-GAT(T/C)-3' as a core sequence. This motif has served to
      construct a synthetic cytokinin-sensitive two-component system response element,
      which is useful for monitoring the cellular cytokinin status. Insight into the
      extent of transcriptional regulation has been gained by genome-wide gene
      expression analyses following cytokinin treatment and from plants having an
      altered cytokinin content or signaling. This review presents a meta analysis of
      such microarray data resulting in a core list of cytokinin response genes. Genes
      encoding type-A response regulators displayed the most stable response to
      cytokinin, but a number of cytokinin metabolism genes (CKX4, CKX5, CYP735A2,
      UGT76C2) also belong to them, indicating homeostatic mechanisms operating at the
      transcriptional level. The cytokinin core response genes are also the target of
      other hormones as well as biotic and abiotic stresses, documenting crosstalk of
      the cytokinin system with other hormonal and environmental signaling pathways.
      The multiple links of cytokinin to diverse functions, ranging from control of
      meristem activity, hormonal crosstalk, nutrient acquisition, and various stress
      responses, are also corroborated by a compilation of genes that have been
      repeatedly found by independent gene expression profiling studies. Such functions
      are, at least in part, supported by genetic studies.

PMID- 22639639
TI  - The Maize PIN Gene Family of Auxin Transporters.
AB  - Auxin is a key regulator of plant development and its differential distribution
      in plant tissues, established by a polar cell to cell transport, can trigger a
      wide range of developmental processes. A few members of the two families of auxin
      efflux transport proteins, PIN-formed (PIN) and P-glycoprotein (ABCB/PGP), have
      so far been characterized in maize. Nine new Zea mays auxin efflux carriers PIN
      family members and two maize PIN-like genes have now been identified. Four
      members of PIN1 (named ZmPIN1a-d) cluster, one gene homologous to AtPIN2
      (ZmPIN2), three orthologs of PIN5 (ZmPIN5a-c), one gene paired with AtPIN8
      (ZmPIN8), and three monocot-specific PINs (ZmPIN9, ZmPIN10a, and ZmPIN10b) were
      cloned and the phylogenetic relationships between early-land plants, monocots,
      and eudicots PIN proteins investigated, including the new maize PIN proteins.
      Tissue-specific expression patterns of the 12 maize PIN genes, 2 PIN-like genes
      and ZmABCB1, an ABCB auxin efflux carrier, were analyzed together with protein
      localization and auxin accumulation patterns in normal conditions and in response
      to drug applications. ZmPIN gene transcripts have overlapping expression domains
      in the root apex, during male and female inflorescence differentiation and kernel
      development. However, some PIN family members have specific tissue localization:
      ZmPIN1d transcript marks the L1 layer of the shoot apical meristem and
      inflorescence meristem during the flowering transition and the monocot-specific
      ZmPIN9 is expressed in the root endodermis and pericycle. The phylogenetic and
      gene structure analyses together with the expression pattern of the ZmPIN gene
      family indicate that subfunctionalization of some maize PINs can be associated to
      the differentiation and development of monocot-specific organs and tissues and
      might have occurred after the divergence between dicots and monocots.

PMID- 22639640
TI  - Catabolism and deactivation of the lipid-derived hormone jasmonoyl-isoleucine.
AB  - The oxylipin hormone jasmonate controls myriad processes involved in plant
      growth, development, and immune function. The discovery of jasmonoyl-l-isoleucine
      (JA-Ile) as the major bioactive form of the hormone highlights the need to
      understand biochemical and cell biological processes underlying JA-Ile
      homeostasis. Among the major metabolic control points governing the accumulation
      of JA-Ile in plant tissues are the availability of jasmonic acid, the immediate
      precursor of JA-Ile, and oxidative enzymes involved in catabolism and
      deactivation of the hormone. Recent studies indicate that JA-Ile turnover is
      mediated by a omega-oxidation pathway involving members of the CYP94 family of
      cytochromes P450. This discovery opens new opportunities to genetically
      manipulate JA-Ile levels for enhanced resistance to environmental stress, and
      further highlights omega-oxidation as a conserved pathway for catabolism of lipid
      derived signals in plants and animals. Functional characterization of the full
      complement of CYP94 P450s promises to reveal new pathways for jasmonate
      metabolism and provide insight into the evolution of oxylipin signaling in land
      plants.

PMID- 22639641
TI  - Evolution of plant sucrose uptake transporters.
AB  - In angiosperms, sucrose uptake transporters (SUTs) have important functions
      especially in vascular tissue. Here we explore the evolutionary origins of SUTs
      by analysis of angiosperm SUTs and homologous transporters in a vascular early
      land plant, Selaginella moellendorffii, and a non-vascular plant, the bryophyte
      Physcomitrella patens, the charophyte algae Chlorokybus atmosphyticus, several
      red algae and fission yeast, Schizosaccharomyces pombe. Plant SUTs cluster into
      three types by phylogenetic analysis. Previous studies using angiosperms had
      shown that types I and II are localized to the plasma membrane while type III
      SUTs are associated with vacuolar membrane. SUT homologs were not found in the
      chlorophyte algae Chlamydomonas reinhardtii and Volvox carterii. However, the
      characean algae Chlorokybus atmosphyticus contains a SUT homolog (CaSUT1) and
      phylogenetic analysis indicated that it is basal to all other streptophyte SUTs
      analyzed. SUTs are present in both red algae and S. pombe but they are less
      related to plant SUTs than CaSUT1. Both Selaginella and Physcomitrella encode
      type II and III SUTs suggesting that both plasma membrane and vacuolar sucrose
      transporter activities were present in early land plants. It is likely that SUT
      transporters are important for scavenging sucrose from the environment and
      intracellular compartments in charophyte and non-vascular plants. Type I SUTs
      were only found in eudicots and we conclude that they evolved from type III SUTs,
      possibly through loss of a vacuolar targeting sequence. Eudicots utilize type I
      SUTs for phloem (vascular tissue) loading while monocots use type II SUTs for
      phloem loading. We show that HvSUT1 from barley, a type II SUT, reverted the
      growth defect of the Arabidopsis atsuc2 (type I) mutant. This indicates that type
      I and II SUTs evolved similar (and interchangeable) phloem loading transporter
      capabilities independently.

PMID- 22639642
TI  - The mode of sucrose degradation in potato tubers determines the fate of
      assimilate utilization.
AB  - Cytosolic (U-IN-2) or apoplasmic (U-IN-1) targeting of yeast invertase in potato
      tubers leads to a reduction in sucrose and an increase in glucose content, but
      specific phenotypical changes are dependent on the subcellular targeting of the
      enzyme. Cytosolic expression leads to a more severe phenotype with the most
      striking aspects being reduced starch content and increased respiration. Despite
      extensive research, the regulatory mechanisms leading to these changes remain
      obscure. Recent technological advancements regarding potato transcriptional and
      genomic research presented us with the opportunity to revisit these lines and
      perform detailed gene expression analysis, in combination with extensive
      metabolic profiling, to identify regulatory networks underlying the observed
      changes. Our results indicate that in both genotypes reduced UDP-glucose
      production is associated with a reduced expression of cell wall biosynthetic
      genes. In addition, U-IN-1 tubers are characterized by elevated expression of
      senescence-associated genes, coupled to reduced expression of genes related to
      photosynthesis and the cytoskeleton. We provide evidence that increased
      respiration, observed specifically in U-IN-2 tubers, might be due to sugar
      signaling via released trehalose-6-phosphate inhibition of the SnRK1 complex. In
      both genotypes, expression of the plastidic glucose-6-phosphate transporter (GPT)
      is significantly down-regulated. This leads to a shift in the cytosolic to
      plastidic glucose-6-phosphate ratio and hence might limit starch synthesis but
      also the oxidative pentose phosphate pathway. This might explain the observed
      changes in several additional plastid localized pathways, most notably reduced
      expression of fatty acid biosynthetic genes and an accumulation of shikimate.
      Interestingly, a strict negative correlation between invertase and GPT expression
      could be observed in a wide range of potato tubers. This reciprocal regulation
      may be part of a more general switch controlling energy versus storage
      metabolism, suggesting that the fate of assimilate utilization is coordinated at
      the level of sucrose degradation.

PMID- 22639643
TI  - Conserved and diversified gene families of monovalent cation/h(+) antiporters
      from algae to flowering plants.
AB  - All organisms have evolved strategies to regulate ion and pH homeostasis in
      response to developmental and environmental cues. One strategy is mediated by
      monovalent cation-proton antiporters (CPA) that are classified in two
      superfamilies. Many CPA1 genes from bacteria, fungi, metazoa, and plants have
      been functionally characterized; though roles of plant CPA2 genes encoding K(+)
      efflux antiporter (KEA) and cation/H(+) exchanger (CHX) families are largely
      unknown. Phylogenetic analysis showed that three clades of the CPA1 Na(+)-H(+)
      exchanger (NHX) family have been conserved from single-celled algae to
      Arabidopsis. These are (i) plasma membrane-bound SOS1/AtNHX7 that share ancestry
      with prokaryote NhaP, (ii) endosomal AtNHX5/6 that is part of the eukaryote
      Intracellular-NHE clade, and (iii) a vacuolar NHX clade (AtNHX1-4) specific to
      plants. Early diversification of KEA genes possibly from an ancestral
      cyanobacterium gene is suggested by three types seen in all plants. Intriguingly,
      CHX genes diversified from three to four members in one subclade of early land
      plants to 28 genes in eight subclades of Arabidopsis. Homologs from Spirogyra or
      Physcomitrella share high similarity with AtCHX20, suggesting that guard cell
      specific AtCHX20 and its closest relatives are founders of the family, and pollen
      expressed CHX genes appeared later in monocots and early eudicots. AtCHX proteins
      mediate K(+) transport and pH homeostasis, and have been localized to
      intracellular and plasma membrane. Thus KEA genes are conserved from green algae
      to angiosperms, and their presence in red algae and secondary endosymbionts
      suggest a role in plastids. In contrast, AtNHX1-4 subtype evolved in plant cells
      to handle ion homeostasis of vacuoles. The great diversity of CHX genes in land
      plants compared to metazoa, fungi, or algae would imply a significant role of ion
      and pH homeostasis at dynamic endomembranes in the vegetative and reproductive
      success of flowering plants.

PMID- 22639644
TI  - Annotation of Selaginella moellendorffii Major Intrinsic Proteins and the
      Evolution of the Protein Family in Terrestrial Plants.
AB  - Major intrinsic proteins (MIPs) also called aquaporins form pores in membranes to
      facilitate the permeation of water and certain small polar solutes across
      membranes. MIPs are present in virtually every organism but are uniquely abundant
      in land plants. To elucidate the evolution and function of MIPs in terrestrial
      plants, the MIPs encoded in the genome of the spikemoss Selaginella
      moellendorffii were identified and analyzed. In total 19 MIPs were found in S.
      moellendorffii belonging to 6 of the 7 MIP subfamilies previously identified in
      the moss Physcomitrella patens. Only three of the MIPs were classified as members
      of the conserved water specific plasma membrane intrinsic protein (PIP) subfamily
      whereas almost half were found to belong to the diverse NOD26-like intrinsic
      protein (NIP) subfamily permeating various solutes. The small number of PIPs in
      S. moellendorffii is striking compared to all other land plants and no other
      species has more NIPs than PIPs. Similar to moss, S. moellendorffii only has one
      type of tonoplast intrinsic protein (TIP). Based on ESTs from non-angiosperms we
      conclude that the specialized groups of TIPs present in higher plants are not
      found in primitive vascular plants but evolved later in a common ancestor of seed
      plants. We also note that the silicic acid permeable NIP2 group that has been
      reported from angiosperms appears at the same time. We suggest that the expansion
      of the number MIP isoforms in higher plants is primarily associated with an
      increase in the different types of specialized tissues rather than the emergence
      of vascular tissue per se and that the loss of subfamilies has been possible due
      to a functional overlap between some subfamilies.

PMID- 22639645
TI  - Grand Challenges in Plant Systems Biology: Closing the Circle(s).

PMID- 22639646
TI  - Amino Acid transporter inventory of the selaginella genome.
AB  - Amino acids play fundamental roles in a multitude of functions including protein
      synthesis, hormone metabolism, nerve transmission, cell growth, production of
      metabolic energy, nucleobase synthesis, nitrogen metabolism, and urea
      biosynthesis. Selaginella as a member of the lycophytes is part of an ancient
      lineage of vascular plants that had arisen ~400 million years ago. In
      angiosperms, which have attracted most of the attention for nutrient transport so
      far, we have been able to identify many of the key transporters for nitrogen.
      Their role is not always fully clear, thus an analysis of Selaginella as a
      representative of an ancient vascular plant may help shed light on the evolution
      and function of these diverse transporters. Here we annotated and analyzed the
      genes encoding putative transporters involved in cellular uptake of amino acids
      present in the Selaginella genome.

PMID- 22639647
TI  - Transgenic Introduction of a Glycolate Oxidative Cycle into A. thaliana
      Chloroplasts Leads to Growth Improvement.
AB  - The photorespiratory pathway helps illuminated C(3)-plants under conditions of
      limited CO(2) availability by effectively exporting reducing equivalents in form
      of glycolate out of the chloroplast and regenerating glycerate-3-P as substrate
      for RubisCO. On the other hand, this pathway is considered as probably futile
      because previously assimilated CO(2) is released in mitochondria. Consequently, a
      lot of effort has been made to reduce this CO(2) loss either by reducing fluxes
      via engineering RubisCO or circumventing mitochondrial CO(2) release by the
      introduction of new enzyme activities. Here we present an approach following the
      latter route, introducing a complete glycolate catabolic cycle in chloroplasts of
      Arabidopsis thaliana comprising glycolate oxidase (GO), malate synthase (MS), and
      catalase (CAT). Results from plants bearing both GO and MS activities have
      already been reported (Fahnenstich et al., 2008). This previous work showed that
      the H(2)O(2) produced by GO had strongly negative effects. These effects can be
      prevented by introducing a plastidial catalase activity, as reported here.
      Transgenic lines bearing all three transgenic enzyme activities were identified
      and some with higher CAT activity showed higher dry weight, higher photosynthetic
      rates, and changes in glycine/serine ratio compared to the wild type. This
      indicates that the fine-tuning of transgenic enzyme activities in the
      chloroplasts seems crucial and strongly suggests that the approach is valid and
      that it is possible to improve the growth of A. thaliana by introducing a
      synthetic glycolate oxidative cycle into chloroplasts.

PMID- 22639648
TI  - Non-Canonical Processing of Arabidopsis pri-miR319a/b/c Generates Additional
      microRNAs to Target One RAP2.12 mRNA Isoform.
AB  - Arabidopsis miR319a/b/c primary transcripts are unusual due to the presence of a
      long stem and loop structure containing functional miR319a/b/c molecules. In our
      experiments carried out using high throughput sequencing (HTS), we have shown
      that additional microRNAs (miRNAs), miR319a.2/b.2/c.2 are generated from the
      upper part of the same hairpin structure. We have also found cognate
      miRNAa.2*/b.2*/c.2* to be present in the HTS results with a considerably lower
      number of reads. Northern hybridization revealed that miR319b.2 is mainly
      expressed in 35-day-old plant rosette leaves, as well as in stem and
      inflorescences of 42- and 53-day-old plants. Moreover, it carries multiple
      signatures of a functional miRNA, including as follows: (i) its biogenesis is
      HYL1-dependent; (ii) it is incorporated in a substantial amount into RISC
      complexes containing AGO1, AGO2, or AGO4 protein; (iii) 24 nt-long species of
      miR319b.2 have been found in inflorescences to be more abundant than 21 nt
      miR319b.2 species; (iv) it is present in various ratios to miR319b during plant
      development, which suggests the existence of a regulatory mechanism responsible
      for its biogenesis/processing; (v) there is an observed cross-species
      conservation of the miR319a/b/c stem nucleotide sequence extending beyond mature
      miRNA region; and (vi) all evidence suggests that intron-containing RAP2.12 mRNA
      isoform is the target for miR319b.2. All these features prompt us to claim
      miR319b.2 as a functional miRNA molecule.

PMID- 22639649
TI  - Adenosine Methylation in Arabidopsis mRNA is Associated with the 3' End and
      Reduced Levels Cause Developmental Defects.
AB  - We previously showed that the N6-methyladenosine (m(6)A) mRNA methylase is
      essential during Arabidopsis thaliana embryonic development. We also demonstrated
      that this modification is present at varying levels in all mature tissues.
      However, the requirement for the m(6)A in the mature plant was not tested. Here
      we show that a 90% reduction in m(6)A levels during later growth stages gives
      rise to plants with altered growth patterns and reduced apical dominance. The
      flowers of these plants commonly show defects in their floral organ number, size,
      and identity. The global analysis of gene expression from reduced m(6)A plants
      show that a significant number of down-regulated genes are involved in transport,
      or targeted transport, and most of the up-regulated genes are involved in stress
      and stimulus response processes. An analysis of m(6)A distribution in fragmented
      mRNA suggests that the m(6)A is predominantly positioned toward the 3' end of
      transcripts in a region 100-150 bp before the poly(A) tail. In addition to the
      analysis of the phenotypic changes in the low methylation Arabidopsis plants we
      will review the latest advances in the field of mRNA internal methylation.

PMID- 22639650
TI  - Crosstalk between Phospholipase D and Sphingosine Kinase in Plant Stress
      Signaling.
AB  - The activation of phospholipase D (PLD) produces phosphatidic acid (PA), whereas
      plant sphingosine kinase (SPHK) phosphorylates long-chain bases to generate long
      chain base-1-phosphates such as phytosphingosine-1-phosphate (phyto-S1P). PA and
      phyto-S1P have been identified as lipid messengers. Recent studies have shown
      that PA interacts directly with SPHKs in Arabidopsis, and that the interaction
      promotes SPHK activity. However, SPHK and phyto-S1P act upstream of PLDalpha1 and
      PA in the stomatal response to abscisic acid (ABA). These findings indicate that
      SPHK/phyto-S1P and PLD/PA are co-dependent in the amplification of lipid
      messengers, and that crosstalk between the sphingolipid- and phospholipid
      mediated signaling pathways may play important roles in plant stress signaling.

PMID- 22639651
TI  - New aspects of Phloem-mediated long-distance lipid signaling in plants.
AB  - Plants are sessile and cannot move to appropriate hiding places or feeding
      grounds to escape adverse conditions. As a consequence, they evolved mechanisms
      to detect changes in their environment, communicate these to different organs,
      and adjust development accordingly. These adaptations include two long-distance
      transport systems which are essential in plants: the xylem and the phloem. The
      phloem serves as a major trafficking pathway for assimilates, viruses, RNA, plant
      hormones, metabolites, and proteins with functions ranging from synthesis to
      metabolism to signaling. The study of signaling compounds within the phloem is
      essential for our understanding of plant communication of environmental cues.
      Determining the nature of signals and the mechanisms by which they are
      communicated through the phloem will lead to a more complete understanding of
      plant development and plant responses to stress. In our analysis of Arabidopsis
      phloem exudates, we had identified several lipid-binding proteins as well as
      fatty acids and lipids. The latter are not typically expected in the aqueous
      environment of sieve elements. Hence, lipid transport in the phloem has been
      given little attention until now. Long-distance transport of hydrophobic
      compounds in an aqueous system is not without precedence in biological systems: a
      variety of lipids is found in human blood and is often bound to proteins. Some
      lipid-protein complexes are transported to other tissues for storage, use,
      modification, or degradation; others serve as messengers and modulate
      transcription factor activity. By simple analogy it raises the possibility that
      lipids and the respective lipid-binding proteins in the phloem serve similar
      functions in plants and play an important role in stress and developmental
      signaling. Here, we introduce the lipid-binding proteins and the lipids we found
      in the phloem and discuss the possibility that they may play an important role in
      developmental and stress signaling.

PMID- 22639652
TI  - Turnover of Phosphatidic Acid through Distinct Signaling Pathways Affects
      Multiple Aspects of Pollen Tube Growth in Tobacco.
AB  - Phosphatidic acid (PA) is an important intermediate in membrane lipid metabolism
      that acts as a key component of signaling networks, regulating the spatio
      temporal dynamics of the endomembrane system and the cytoskeleton. Using tobacco
      pollen tubes as a model, we addressed the signaling effects of PA by probing the
      functions of three most relevant enzymes that regulate the production and
      degradation of PA, namely, phospholipases D (PLD), diacylglycerol kinases (DGKs),
      and lipid phosphate phosphatases (LPPs). Phylogenetic analysis indicated a highly
      dynamic evolution of all three lipid-modifying enzymes in land plants, with many
      clade-specific duplications or losses and massive diversification of the C2-PLD
      family. In silico transcriptomic survey revealed increased levels of expression
      of all three PA-regulatory genes in pollen development (particularly the DGKs).
      Using specific inhibitors we were able to distinguish the contributions of PLDs,
      DGKs, and LPPs into PA-regulated processes. Thus, suppressing PA production by
      inhibiting either PLD or DGK activity compromised membrane trafficking except
      early endocytosis, disrupted tip-localized deposition of cell wall material,
      especially pectins, and inhibited pollen tube growth. Conversely, suppressing PA
      degradation by inhibiting LPP activity using any of three different inhibitors
      significantly stimulated pollen tube growth, and similar effect was achieved by
      suppressing the expression of tobacco pollen LPP4 using antisense knock-down.
      Interestingly, inhibiting specifically DGK changed vacuolar dynamics and the
      morphology of pollen tubes, whereas inhibiting specifically PLD disrupted the
      actin cytoskeleton. Overall, our results demonstrate the critical importance of
      all three types of enzymes involved in PA production and degradation, with
      strikingly different roles of PA produced by the PLD and DGK pathways, in pollen
      tube growth.

PMID- 22639653
TI  - The Role of the P1BS Element Containing Promoter-Driven Genes in Pi Transport and
      Homeostasis in Plants.
AB  - Inorganic phosphate (Pi) is an easily accessible form of phosphorus for plants.
      Plant Pi uptake is usually limited however by slow Pi diffusion through the soil
      which strongly adsorps phosphate species. Plants have developed mechanisms to
      increase Pi availability. There are also abiotic (phosphate level) and biotic
      (e.g., mycorrhizal) factors regulating the expression of Pi-responsive genes.
      Transcription factors binding to the promoters of Pi-responsive genes activate
      different pathways of Pi transport, distribution, and homeostasis maintenance. Pi
      metabolism involves not only functional proteins but also microRNAs and other non
      coding RNAs.

PMID- 22639654
TI  - The rice diacylglycerol kinase family: functional analysis using transient RNA
      interference.
AB  - Diacylglycerol kinase (DGK) is a pivotal enzyme that phosphorylates
      diacylglycerol (DAG) to form phosphatidic acid (PA). The production of PA from
      phospholipase D (PLD) and the coupled phospholipase C/DGK route is an important
      signaling process in animal and plant cells. In this study, we report a genomic
      analysis of eight putative rice DGKs encoded by a gene family (OsDGKs) grouped
      into three clusters. To further investigate the functions of the OsDGKs, a double
      stranded RNA (dsRNA)-induced RNA silencing method was established. Introduction
      of in vitro-synthesized dsRNAs corresponding to a unique or conserved region of
      OsDGKs into rice protoplasts abolished or diminished the expression of individual
      or multiple OsDGK genes. Suppressing the expression of OsDGKs resulted in a
      distinct depletion of the transcripts of the defense gene OsNPR1 and the salt
      responsive gene OsCIPK15. Our primary results suggest that OsDGKs are involved in
      the signaling of stress responses.

PMID- 22639655
TI  - Ammonium and urea transporter inventory of the selaginella and physcomitrella
      genomes.
AB  - Ammonium and urea are important nitrogen sources for autotrophic organisms. Plant
      genomes encode several families of specific transporters for these molecules,
      plus other uptake mechanisms such as aquaporins and ABC transporters. Selaginella
      and Physcomitrella are representatives of lycophytes and bryophytes,
      respectively, and the recent completion of their genome sequences provided us
      with an opportunity for comparative genome studies, with special emphasis on the
      adaptive processes that accompanied the conquest of dry land and the evolution of
      a vascular system. Our phylogenetic analysis revealed that the number of genes
      encoding urea transporters underwent a progressive reduction during evolution,
      eventually down to a single copy in vascular plants. Conversely, no clear
      evolutionary pattern was found for ammonium transporters, and their number and
      distribution in families varies between species. In particular Selaginella,
      similar to rice, favors the AMT2/MEP family of ammonium transporters over the
      plant-specific AMT1 type. In comparison, Physcomitrella presents several members
      belonging to both families.

PMID- 22639656
TI  - Species composition and fire: non-additive mixture effects on ground fuel
      flammability.
AB  - Diversity effects on many aspects of ecosystem function have been well
      documented. However, fire is an exception: fire experiments have mainly included
      single species, bulk litter, or vegetation, and, as such, the role of diversity
      as a determinant of flammability, a crucial aspect of ecosystem function, is
      poorly understood. This study is the first to experimentally test whether
      flammability characteristics of two-species mixtures are non-additive, i.e.,
      differ from expected flammability based on the component species in monospecific
      fuel. In standardized fire experiments on ground fuels, including monospecific
      fuels and mixtures of five contrasting subarctic plant fuel types in a controlled
      laboratory environment, we measured flame speed, flame duration, and maximum
      temperature. Broadly half of the mixture combinations showed non-additive effects
      for these flammability indicators; these were mainly enhanced dominance effects
      for temporal dynamics - fire speed and duration. Fuel types with the more
      flammable value for a characteristic determined the rate of fire speed and
      duration of the whole mixture; in contrast, maximum temperature of the fire was
      determined by the biomass-weighted mean of the mixture. These results suggest
      that ecological invasions by highly flammable species may have effects on ground
      fire dynamics well out of proportion to their biomass.

PMID- 22639657
TI  - The Rice Proteogenomics Database OryzaPG-DB: Development, Expansion, and New
      Features.
AB  - Our recently developed rice proteogenomics database (OryzaPG-DB) is the first
      sustainable resource for rice shotgun-based proteogenomics, providing information
      on peptides identified in rice protein digested peptides measured by means of
      liquid chromatography-tandem mass spectrometry (LC-MS/MS), and mapping of the
      peptides to their genomic origins and the genomic novelty of each peptide. The
      sequences of the peptides, proteins, cDNAs and genes, and the gene annotations
      are available for download in FASTA and GFF3 formats, respectively. Further, an
      annotated visualization of the gene models, corresponding peptides, and genomic
      novelty is available for each gene, and MS/MS spectra are available for each
      peptide. In this article, we discuss the utilization of OryzaPG-DB and report on
      its development, recent content expansions, and newly added features in the
      current version (OryzaPG-DB v1.1).

PMID- 22639659
TI  - myo-Inositol Oxygenase is Required for Responses to Low Energy Conditions in
      Arabidopsis thaliana.
AB  - myo-Inositol is a precursor for cell wall components, is used as a backbone of
      myo-inositol trisphosphate (Ins(1,4,5)P(3)) and phosphatidylinositol phosphate
      signaling molecules, and is debated about whether it is also a precursor in an
      alternate ascorbic acid synthesis pathway. Plants control inositol homeostasis by
      regulation of key enzymes involved in myo-inositol synthesis and catabolism.
      Recent transcriptional profiling data indicate up-regulation of the myo-inositol
      oxygenase (MIOX) genes under conditions in which energy or nutrients are limited.
      To test whether the MIOX genes are required for responses to low energy, we first
      examined MIOX2 and MIOX4 gene expression regulation by energy/nutrient
      conditions. We found that both MIOX2 and MIOX4 expression are suppressed by
      exogenous glucose addition in the shoot, but not in the root. Both genes were
      abundantly expressed during low energy/nutrient conditions. Loss-of-function
      mutants in MIOX genes contain alterations in myo-inositol levels and growth
      changes in the root. Miox2 mutants can be complemented with a MIOX2:green
      fluorescent protein fusion. Further we show here that MIOX2 is a cytoplasmic
      protein, while MIOX4 is present mostly in the cytoplasm, but also occasionally in
      the nucleus. Together, these data suggest that MIOX catabolism in the shoot may
      influence root growth responses during low energy/nutrient conditions.

PMID- 22639660
TI  - A model for the biosynthesis and transport of plasma membrane-associated
      signaling receptors to the cell surface.
AB  - Intracellular protein transport is emerging as critical in determining the
      outcome of receptor-activated signal transduction pathways. In plants, relatively
      little is known about the nature of the molecular components and mechanisms
      involved in coordinating receptor synthesis and transport to the cell surface.
      Recent advances in this field indicate that signaling pathways and intracellular
      transport machinery converge and coordinate to render receptors competent for
      signaling at their plasma membrane (PM) activity sites. The biogenesis and
      transport to the cell surface of signaling receptors appears to require both
      general trafficking and receptor-specific factors. Several molecular
      determinants, residing or associated with compartments of the secretory pathway
      and known to influence aspects in receptor biogenesis, are discussed and
      integrated into a predictive cooperative model for the functional expression of
      signaling receptors at the PM.

PMID- 22639658
TI  - Sphingolipids and plant defense/disease: the "death" connection and beyond.
AB  - Sphingolipids comprise a major class of structural materials and lipid signaling
      molecules in all eukaryotic cells. Over the past two decades, there has been a
      phenomenal growth in the study of sphingolipids (i.e., sphingobiology) at an
      average rate of ~1000 research articles per year. Sphingolipid studies in plants,
      though accounting for only a small fraction (~6%) of the total number of
      publications, have also enjoyed proportionally rapid growth in the past decade.
      Concomitant with the growth of sphingobiology, there has also been tremendous
      progress in our understanding of the molecular mechanisms of plant innate
      immunity. In this review, we (i) cross examine and analyze the major findings
      that establish and strengthen the intimate connections between sphingolipid
      metabolism and plant programmed cell death (PCD) associated with plant defense or
      disease; (ii) highlight and compare key bioactive sphingolipids involved in the
      regulation of plant PCD and possibly defense; (iii) discuss the potential role of
      sphingolipids in polarized membrane/protein trafficking and formation of lipid
      rafts as subdomains of cell membranes in relation to plant defense; and (iv)
      where possible, attempt to identify potential parallels for immunity-related
      mechanisms involving sphingolipids across kingdoms.

PMID- 22639661
TI  - Building Qualitative Models of Plant Regulatory Networks with SQUAD.

PMID- 22639662
TI  - Transcriptional Regulation of Grass Secondary Cell Wall Biosynthesis: Playing
      Catch-Up with Arabidopsis thaliana.
AB  - Secondary cell wall synthesis occurs in specialized cell types following
      completion of cell enlargement. By virtue of mechanical strength provided by a
      wall thickened with cellulose, hemicelluloses, and lignin, these cells can
      function as water-conducting vessels and provide structural support. Several
      transcription factor families regulate genes encoding wall synthesis enzymes.
      Certain NAC and MYB proteins directly bind to the SNBE and AC elements upstream
      of structural genes and other transcription factors. The most detailed model of
      this regulatory network is established predominantly for a eudicot, Arabidopsis
      thaliana. In grasses, both the patterning and the composition of secondary cell
      walls are distinct from that of eudicots. These differences suggest
      transcriptional regulation is similarly distinct. Putative rice and maize
      orthologs of several eudicot cell wall regulators genetically complement mutants
      of A. thaliana or result in wall defects when constitutively overexpressed;
      nevertheless, aside from a maize, ZmMYB31, and a switchgrass protein, PvMYB4,
      function has not been tested in a grass. Similar to the seminal work conducted in
      A. thaliana, gene expression profiling in maize, rice, and other grasses
      implicates additional genes as regulators. Characterization of these genes will
      continue to elucidate the relationship between the transcription regulatory
      networks of eudicots and grasses.

PMID- 22639663
TI  - Cellulose synthase complexes: composition and regulation.
AB  - Live cell imaging has greatly advanced our knowledge on the molecular mechanism
      by which cellulose is deposited. Both the actin and microtubule cytoskeleton are
      involved in assuring the proper distribution, organization, and dynamics of
      cellulose synthase complexes (CSCs). This review is an update on the most recent
      progress on the characterization of the composition, regulation, and trafficking
      of CSCs. With the newly identified cellulose synthase interactive protein 1
      (CSI1) on hand, we begin to unveil the mystery of an intimate relationship
      between cellulose microfibrils and microtubules.

PMID- 22639664
TI  - An expanding role for purine uptake permease-like transporters in plant secondary
      metabolism.
AB  - For the past decade, our understanding of the plant purine uptake permease (PUP)
      transporter family was primarily oriented on purine nucleobase substrates and
      their tissue-specific expression patterns in Arabidopsis. However, a tobacco PUP
      like homolog demonstrating nicotine uptake permease activity was recently shown
      to affect both nicotine metabolism and root cell growth. These new findings
      expand the physiological role for PUP-like transporters to include plant
      secondary metabolism. Molecular evolution analyses of PUP-like transporters
      indicate they are distinct group within an ancient super family of drug and
      metabolite transporters (DMTs). The PUP-like family originated during terrestrial
      plant evolution sometime between the bryophytes and the lycophytes. A
      phylogenetic analysis indicates that the PUP-like transporters were likely
      derived from a pre-existing nucleotide-sugar transporter family within the DMT
      super family. Within the lycophyte Selaginella, there are three paralogous groups
      of PUP-like transporters. One of the three PUP-like paralogous groups showed an
      extensive pattern of gene duplication and diversification within the angiosperm
      lineage, whereas the more ancestral PUP-like paralogous groups did not.
      Biochemical characterization of four closely related PUP-like paralogs together
      with model-based phylogenetic analyses indicate both subfunctionalization and
      neofunctionalization during the molecular evolution of angiosperm PUP-like
      transporters. These findings suggest that members of the PUP-like family of DMT
      transporters are likely involved in diverse primary and secondary plant metabolic
      pathways.

PMID- 22639665
TI  - Golgi-mediated synthesis and secretion of matrix polysaccharides of the primary
      cell wall of higher plants.
AB  - The Golgi apparatus of eukaryotic cells is known for its central role in the
      processing, sorting, and transport of proteins to intra- and extra-cellular
      compartments. In plants, it has the additional task of assembling and exporting
      the non-cellulosic polysaccharides of the cell wall matrix including pectin and
      hemicelluloses, which are important for plant development and protection. In this
      review, we focus on the biosynthesis of complex polysaccharides of the primary
      cell wall of eudicotyledonous plants. We present and discuss the compartmental
      organization of the Golgi stacks with regards to complex polysaccharide assembly
      and secretion using immuno-electron microscopy and specific antibodies
      recognizing various sugar epitopes. We also discuss the significance of the
      recently identified Golgi-localized glycosyltransferases responsible for the
      biosynthesis of xyloglucan (XyG) and pectin.

PMID- 22639667
TI  - The Cell Walls of Green Algae: A Journey through Evolution and Diversity.
AB  - The green algae represent a large group of morphologically diverse photosynthetic
      eukaryotes that occupy virtually every photic habitat on the planet. The
      extracellular coverings of green algae including cell walls are also diverse. A
      recent surge of research in green algal cell walls fueled by new emerging
      technologies has revealed new and critical insight concerning these coverings.
      For example, the late divergent taxa of the Charophycean green algae possess cell
      walls containing assemblages of polymers with notable similarity to the
      cellulose, pectins, hemicelluloses, arabinogalactan proteins (AGPs), extensin,
      and lignin present in embryophyte walls. Ulvophycean seaweeds have cell wall
      components whose most abundant fibrillar constituents may change from cellulose
      to beta-mannans to beta-xylans and during different life cycle phases. Likewise,
      these algae produce complex sulfated polysaccharides, AGPs, and extensin.
      Chlorophycean green algae produce a wide array of walls ranging from cellulose
      pectin complexes to ones made of hydroxyproline-rich glycoproteins. Larger and
      more detailed surveys of the green algal taxa including incorporation of emerging
      genomic and transcriptomic data are required in order to more fully resolve
      evolutionary trends within the green algae and in relationship with higher plants
      as well as potential applications of wall components in the food and
      pharmaceutical industries.

PMID- 22639666
TI  - The Role of Polypyrimidine Tract-Binding Proteins and Other hnRNP Proteins in
      Plant Splicing Regulation.
AB  - Alternative precursor mRNA splicing is a widespread phenomenon in multicellular
      eukaryotes and represents a major means for functional expansion of the
      transcriptome. While several recent studies have revealed an important link
      between splicing regulation and fundamental biological processes in plants, many
      important aspects, such as the underlying splicing regulatory mechanisms, are so
      far not well understood. Splicing decisions are in general based on a splicing
      code that is determined by the dynamic interplay of splicing-controlling factors
      and cis-regulatory elements. Several members of the group of heterogeneous
      nuclear ribonucleoprotein (hnRNP) proteins are well known regulators of splicing
      in animals and the comparatively few reports on some of their plant homologs
      revealed similar functions. This also applies to polypyrimidine tract-binding
      proteins, a thoroughly investigated class of hnRNP proteins with splicing
      regulatory functions in both animals and plants. Further examples from plants are
      auto- and cross-regulatory splicing circuits of glycine-rich RNA binding proteins
      and splicing enhancement by oligouridylate binding proteins. Besides their role
      in defining splice site choice, hnRNP proteins are also involved in multiple
      other steps of nucleic acid metabolism, highlighting the functional versatility
      of this group of proteins in higher eukaryotes.

PMID- 22639668
TI  - Deciphering the molecular functions of sterols in cellulose biosynthesis.
AB  - Sterols play vital roles in plant growth and development, as components of
      membranes and as precursors to steroid hormones. Analysis of Arabidopsis mutants
      indicates that sterol composition is crucial for cellulose biosynthesis. Sterols
      are widespread in the plasma membrane (PM), suggesting a possible link between
      sterols and the multimeric cellulose synthase complex. In one possible scenario,
      molecular interactions in sterol-rich PM microdomains or another form of sterol
      dependent membrane scaffolding may be critical for maintaining the correct
      subcellular localization, structural integrity and/or activity of the cellulose
      synthase machinery. Another possible link may be through steryl glucosides, which
      could act as primers for the attachment of glucose monomers during the synthesis
      of beta-(1 -> 4) glucan chains that form the cellulose microfibrils. This mini
      review examines genetic and biochemical data supporting the link between sterols
      and cellulose biosynthesis in cell wall formation and explores potential
      approaches to elucidate the mechanism of this association.

PMID- 22639669
TI  - The plant cell wall: a dynamic barrier against pathogen invasion.
AB  - Prospective plant pathogens must overcome the physical barrier presented by the
      plant cell wall. In addition to being a preformed, passive barrier limiting
      access of pathogens to plant cells, the cell wall is actively remodeled and
      reinforced specifically at discrete sites of interaction with potentially
      pathogenic microbes. Active reinforcement of the cell wall through the deposition
      of cell wall appositions, referred to as papillae, is an early response to
      perception of numerous categories of pathogens including fungi and bacteria.
      Rapid deposition of papillae is generally correlated with resistance to fungal
      pathogens that attempt to penetrate plant cell walls for the establishment of
      feeding structures. Despite the ubiquity and apparent importance of this early
      defense response, relatively little is known about the underlying molecular
      mechanisms and cellular processes involved in the targeting and assembly of
      papillae. This review summarizes recent advances in our understanding of cell
      wall-associated defenses induced by pathogen perception as well as the impact of
      changes in cell wall polymers on interactions with pathogens and highlights
      significant unanswered questions driving future research in the area.

PMID- 22639670
TI  - Phosphorylation of intrinsically disordered regions in remorin proteins.
AB  - Plant-specific remorin proteins reside in subdomains of plasma membranes,
      originally termed membrane rafts. They probably facilitate cellular signal
      transduction by direct interaction with signaling proteins such as receptor-like
      kinases and may dynamically modulate their lateral segregation within plasma
      membranes. Recent evidence suggests such functions of remorins during plant
      microbe interactions and innate immune responses, where differential
      phosphorylation of some of these proteins has been described to be dependent on
      the perception of the microbe-associated molecular pattern (MAMP) flg22 and the
      presence of the NBS-LRR resistance protein RPM1. A number of specifically
      phosphorylated residues in their highly variable and intrinsically disordered N
      terminal regions have been identified. Sequence diversity of these evolutionary
      distinct domains suggests that remorins may serve a wide range of biological
      functions. Here, we describe patterns and features of intrinsic disorder in
      remorin protein and discuss possible functional implications of phosphorylation
      within these rapidly evolving domains.

PMID- 22639671
TI  - Functional Annotation of 2D Protein Maps: The GelMap Portal.
AB  - In classical proteome analyses, final experimental data are (a) images of 2D
      protein separations obtained by gel electrophoresis and (b) corresponding lists
      of proteins which were identified by mass spectrometry (MS). For data annotation,
      software tools were developed which allow the linking of protein identity data
      directly to 2D gels ("clickable gels"). GelMap is a new online software tool to
      annotate 2D protein maps. It allows (i) functional annotation of all identified
      proteins according to biological categories defined by the user, e.g.,
      subcellular localization, metabolic pathway, or assignment to a protein complex
      and (ii) annotation of several proteins per analyzed protein "spot" according to
      MS primary data. Options to differentially display proteins of functional
      categories offer new opportunities for data evaluation. For instance, if used for
      the annotation of 2D Blue native/SDS gels, GelMap allows the identification of
      protein complexes of low abundance. A web portal has been established for
      presentation and evaluation of protein identity data related to 2D gels and is
      freely accessible at http://www.gelmap.de/.

PMID- 22639672
TI  - The cell wall-associated kinases, WAKs, as pectin receptors.
AB  - The wall-associated kinases, WAKs, are encoded by five highly similar genes
      clustered in a 30-kb locus in Arabidopsis. These receptor-like proteins contain a
      cytoplasmic serine threonine kinase, a transmembrane domain, and a less conserved
      region that is bound to the cell wall and contains a series of epidermal growth
      factor repeats. Evidence is emerging that WAKs serve as pectin receptors, for
      both short oligogalacturonic acid fragments generated during pathogen exposure or
      wounding, and for longer pectins resident in native cell walls. This ability to
      bind and respond to several types of pectins correlates with a demonstrated role
      for WAKs in both the pathogen response and cell expansion during plant
      development.

PMID- 22639673
TI  - Small molecule probes for plant cell wall polysaccharide imaging.
AB  - Plant cell walls are composed of interlinked polymer networks consisting of
      cellulose, hemicelluloses, pectins, proteins, and lignin. The ordered deposition
      of these components is a dynamic process that critically affects the development
      and differentiation of plant cells. However, our understanding of cell wall
      synthesis and remodeling, as well as the diverse cell wall architectures that
      result from these processes, has been limited by a lack of suitable chemical
      probes that are compatible with live-cell imaging. In this review, we summarize
      the currently available molecular toolbox of probes for cell wall polysaccharide
      imaging in plants, with particular emphasis on recent advances in small molecule
      based fluorescent probes. We also discuss the potential for further development
      of small molecule probes for the analysis of cell wall architecture and dynamics.

PMID- 22639674
TI  - Heritable Effect of Plant Water Availability Conditions on Restoration of Male
      Fertility in the "9E" CMS-Inducing Cytoplasm of Sorghum.
AB  - Heritable changes of phenotype arising in plant ontogenesis by the influence of
      environmental factors belong to the most intriguing genetic phenomena. An unusual
      inheritance pattern was detected during examination of male fertility restoration
      in the CMS-inducing "9E" type cytoplasm of sorghum: Rf-genes were functional in
      self-pollinated progeny of F(1) hybrids yet were either not expressed or poorly
      expressed in backcrosses of these hybrids to CMS-lines with the same cytoplasm
      type. In experiments on parallel growing of the same F(1) hybrid combinations in
      the "dry plot" and in the "irrigated plot," it was found that high level of plant
      water availability during panicle and pollen developmental stages significantly
      increased male fertility of F(1) and test-cross hybrid populations, in which
      fertility-restoring genes were in heterozygote state, whereas in F(2) populations
      the influences of water availability conditions cause less pronounce effects.
      Similarly, male-sterile F(1) plants, being transferred from the "dry plot" to
      greenhouse, produced male-fertile panicles. In addition, male-sterile plants from
      F(2) families, which segregated-out as recessives, being transferred to
      greenhouse also produced male-fertile panicles. In the progenies of these
      revertants that were grown in field conditions and in the "dry plot," stable
      inheritance of male fertility for three cycles of self-pollination was observed,
      and a number of stable fertile lines in the "9E" cytoplasm were obtained.
      However, in test-crosses of these fertile lines to CMS-lines with the "9E"
      cytoplasm restoration of male fertility was not observed, except the progeny of
      one revertant that behaved as fertility-restorer line. These data suggest that
      the functional state of fertility-restoring genes for the "9E" sorghum cytoplasm
      is epigenetically regulated trait established by the influence of environmental
      factors and is transmitted to sexual generations.

PMID- 22639675
TI  - The Synthesis and Origin of the Pectic Polysaccharide Rhamnogalacturonan II -
      Insights from Nucleotide Sugar Formation and Diversity.
AB  - There is compelling evidence showing that the structurally complex pectic
      polysaccharide rhamnogalacturonan II (RG-II) exists in the primary cell wall as a
      borate cross-linked dimer and that this dimer is required for the assembly of a
      functional wall and for normal plant growth and development. The results of
      several studies have also established that RG-II structure and cross-linking is
      conserved in vascular plants and that RG-II likely appeared early in the
      evolution of land plants. Two features that distinguish RG-II from other plant
      polysaccharides are that RG-II is composed of 13 different glycoses linked to
      each other by up to 22 different glycosidic linkages and that RG-II is the only
      polysaccharide known to contain both apiose and aceric acid. Thus, one key event
      in land plant evolution was the emergence of genes encoding nucleotide sugar
      biosynthetic enzymes that generate the activated forms of apiose and aceric acid
      required for RG-II synthesis. Many of the genes involved in the generation of the
      nucleotide sugars used for RG-II synthesis have been functionally characterized.
      By contrast, only one glycosyltransferase involved in the assembly of RG-II has
      been identified. Here we provide an overview of the formation of the activated
      sugars required for RG-II synthesis and point to the possible cellular and
      metabolic processes that could be involved in assembling and controlling the
      formation of a borate cross-linked RG-II molecule. We discuss how nucleotide
      sugar synthesis is compartmentalized and how this may control the flux of
      precursors to facilitate and regulate the formation of RG-II.

PMID- 22639676
TI  - Recent Advances on the Posttranslational Modifications of EXTs and Their Roles in
      Plant Cell Walls.
AB  - The genetic set up and the enzymes that define the O-glycosylation sites and
      transfer the activated sugars to cell wall glycoprotein Extensins (EXTs) have
      remained unknown for a long time. We are now beginning to see the emerging
      components of the molecular machinery that assembles these complex O
      glycoproteins on the plant cell wall. Genes conferring the posttranslational
      modifications, i.e., proline hydroxylation and subsequent O-glycosylation, of the
      EXTs have been recently identified. In this review we summarize the enzymes that
      define the O-glycosylation sites on the O-glycoproteins, i.e., the prolyl 4
      hydroxylases (P4Hs), the glycosyltransferases that transfer arabinose units
      (named arabinosyltransferases, AraTs), and the one responsible for transferring a
      single galactose (galactosyltransferase, GalT) on the protein EXT backbones. We
      discuss the effects of posttranslational modifications on the structure and
      function of extensins in plant cell walls.

PMID- 22639678
TI  - The Law of Communicable Diseases Act and disclosure to sexual partners among HIV
      positive youth.
AB  - In Sweden, human immunodeficiency virus (HIV) is included among the venereal
      diseases covered by the Law of Communicable Diseases Act. HIV-positive (HIV(+))
      people are required to inform their sexual partners about their infection and
      adopt safe sex behaviours. However, it is unclear how the law is perceived. This
      study explores how HIV(+) youth in Sweden perceive the law, handle their
      sexuality and disclose their HIV diagnosis to sexual partners. Ten HIV(+) women
      and men between 17 and 24 years of age were recruited from three different HIV
      infection clinics. These participants were interviewed in depth. The interviews
      were tape-recorded, transcribed verbatim and analysed according to a grounded
      theory approach. The core category-cultured to take responsibility-illuminates
      the informants' double-edged experiences regarding the law and how they handle
      disclosure to sexual partners. The legislation implies both support and burden
      for these HIV(+) youth; they feel that they have a great deal of responsibility,
      sometimes more than they can handle. 'Switch off lust', 'balancing lust, fear and
      obedience' and 'switch off the disease' are strategies that describe how the
      informants manage sexuality and disclosure. Young HIV(+) people have a difficult
      time informing partners of their HIV diagnosis and discussing safe sex
      strategies. These are challenges that health care providers need to take
      seriously. HIV(+) youth need better communication strategies to negotiate safer
      sex. Staff with extended education on sexuality should be a part of HIV health
      care.

PMID- 22639677
TI  - Escape from preferential retention following repeated whole genome duplications
      in plants.
AB  - The well supported gene dosage hypothesis predicts that genes encoding proteins
      engaged in dose-sensitive interactions cannot be reduced back to single copies
      once all interacting partners are simultaneously duplicated in a whole genome
      duplication. The genomes of extant flowering plants are the result of many
      sequential rounds of whole genome duplication, yet the fraction of genomes
      devoted to encoding complex molecular machines does not increase as fast as
      expected through multiple rounds of whole genome duplications. Using parallel
      interspecies genomic comparisons in the grasses and crucifers, we demonstrate
      that genes retained as duplicates following a whole genome duplication have only
      a 50% chance of being retained as duplicates in a second whole genome
      duplication. Genes which fractionated to a single copy following a second whole
      genome duplication tend to be the member of a gene pair with less complex
      promoters, lower levels of expression, and to be under lower levels of purifying
      selection. We suggest the copy with lower levels of expression and less purifying
      selection contributes less to effective gene-product dosage and therefore is
      under less dosage constraint in future whole genome duplications, providing an
      explanation for why flowering plant genomes are not overrun with subunits of
      large dose-sensitive protein complexes.

PMID- 22639680
TI  - How can we as researchers enhance the quality of our studies?

PMID- 22639679
TI  - Changes in immune function in asthma in the elderly.
AB  - Asthma is an inflammatory disorder of the airway. The airway inflammation of
      asthma is typically an allergic inflammation characterized by cells and mediators
      described as a "Th2" inflammatory response. There is a growing body of evidence
      describing changes in the function of immune cells upon aging, a phenomenon
      referred to as "immunosenescence". Several studies utilizing animal models and
      human subjects with asthma have begun to explore age-related effects on the
      airway inflammation in asthma. This review explores the existing data on the
      presence and effects of immunosenescence or age-related changes in immune
      function in asthma.

PMID- 22639681
TI  - The Need for a Broader Approach to Emotion Regulation Research in Autism.
AB  - Maladaptive emotional reactions are common among individuals diagnosed with an
      autism spectrum disorder (ASD) and often impair functioning. Most research on
      emotional processes in ASD has focused on the recognition of emotion in others.
      This article argues for a broader approach to affective research in ASD, one that
      includes investigations into emotional reactivity and regulation. For example,
      research has typically looked at perseveration in ASD from a cognitive or
      perceptual perspective, yet perseveration also appears to have emotional aspects.
      This article discusses examples of emotion regulation research in other
      populations to illustrate how this approach could inform understanding of
      perseveration in ASD, particularly related to affective interference with
      cognitive control. More broadly, it highlights the potential contributions of
      emotion regulation research in ASD in relation to improving treatment
      specificity, increasing understanding of individual differences and diagnostic
      conceptualizations, and, potentially, contributing to a deeper understanding the
      neurobehavioral underpinnings of ASD.

PMID- 22639683
TI  - The role of young neurosurgeons in the development of neurosurgery.

PMID- 22639682
TI  - Age Trends in Visual Exploration of Social and Nonsocial Information in Children
      with Autism.
AB  - Because previous studies of attention in autism spectrum disorders (ASD) have
      been restricted in age range examined, little is known about how these processes
      develop over the course of childhood. In this study we examined cross-sectional
      age effects on patterns of visual attention to social and nonsocial information
      in 43 typically developing children and 51 children with ASD ranging in age from
      2 to 18. Results indicated a sharp increase in visual exploration with age and a
      decrease in perseverative and detail-focused attention for both groups of
      children. However, increased age was associated with greater increases in visual
      exploration for typically developing children than for those children with ASD.
      The developmental differences were most pronounced for attention to certain
      nonsocial stimuli as children with ASD demonstrated a disproportionate
      attentional bias for these stimuli from very early in life. Disproportionate
      visual attention to certain nonsocial objects relative to social stimuli in ASD
      spanned from early to late childhood, and thus may represent both an early and a
      persistent characteristic of the disorder.

PMID- 22639685
TI  - Endoscopic anatomy of the velum interpositum: A sequential descriptive anatomical
      study.
AB  - BACKGROUND: The velum interpositum and structures lying within and over it
      undergo morbid anatomical changes with hydrocephalus that have not been mentioned
      in the literature. OBJECTIVES: The aim of this article is to describe the diverse
      endoscopic anatomical findings for this surgically important region. MATERIALS
      AND METHODS: One thousand five hundred and twenty cranial endoscopic procedures
      performed from September 1993 till March 2011 have been retrospectively reviewed.
      Anatomical 'situm and covering layers have been reported in 40 cases. RESULTS:
      The changes of the velum interpositum have four patterns. These are 1-Distraction
      mounting to disruption of layers, 2-Reverse in the normal curvature, 3-Reverse of
      the triangular shape with change in size, and 4-Cystic dilatation causing
      hydrocephalus. CONCLUSION: The velum interpositum and roof of the third ventricle
      are sites of changes associated with hydrocephalus that show specific patterns
      described in a sequential anatomical study.

PMID- 22639684
TI  - Posterior inferior cerebellar artery aneurysms: Anatomical variations and
      surgical strategies.
AB  - CONTEXT: Posterior inferior cerebellar artery (PICA) aneurysms are associated
      with multiple anatomical variations of the parent vessel. Complexities in their
      surgical clipping relate to narrow corridors limited by brain-stem, petrous
      occipital bones, and multiple neurovascular structures occupying the
      cerebellomedullary and cerebellopontine cisterns. AIMS: The present study focuses
      on surgical considerations during clipping of saccular PICA aneurysms. SETTING
      AND DESIGN: Tertiary care, retrospective study. MATERIALS AND METHODS: In 20
      patients with PICA aneurysms, CT angiogram/digital substraction angiogram was
      used to correlate the site and anatomical variations of aneurysms located on
      different segments of PICA with the approach selected, the difficulties
      encountered and the final outcome. STATISTICAL ANALYSIS: Comparison of means and
      percentages. RESULTS: ANEURYSMS WERE LOCATED ON PICA AT: vertebral artery/basilar
      artery (VA/BA)-PICA (n=5); anterior medullary (n=4); lateral medullary (n=3);
      tonsillomedullary (n=4); and, telovelotonsillar (n=4) segments. The Hunt and Hess
      grade distribution was I in 15; II in 2; and, III in 3 patients (mean ictus
      surgery interval: 23.5 days; range: 3-150 days). Eight patients had
      hydrocephalus. Anatomical variations included giant, thrombosed aneurysms; 2 PICA
      aneurysms proximal to an arteriovenous malformation; bilobed or multiple
      aneurysms; low PICA situated at the foramen magnum with a hypoplastic VA; and
      fenestrated PICA. The approaches included a retromastoid suboccipital craniectomy
      (n=9); midline suboccipital craniectomy (n=6); and far-lateral approach (n=5). At
      a follow-up (range 6 months-2.5 years), 13 patients had no deficits (modified
      Rankin score (mRS) 0); 2 were symptomatic with no significant disability (mRS1);
      1 had mild disability (mRS2); 1 had moderately severe disability (mRS4); and 3
      died (mRS6). Three mortalities were caused by vasospasm (2) and, rupture of
      unclipped second VA-BA junctional aneurysm (1). CONCLUSIONS: PICA aneurysms may
      present with only IV(th) ventricular blood without subarachnoid hemorrhage. PICA
      may have multiple anomalies and its aneurysms may be missed on CT angiograms.
      Surgical approach is influenced by VA-BA tortuosity and variations in anatomy,
      location of the VA-BA junction and the PICA aneurysm relative to the brain-stem,
      and the pattern of collateral supply. The special category of VA-PICA junctional
      aneurysms and its management; and, the multiple anatomical variations of PICA
      aneurysms, merit special surgical considerations and have been highlighted in
      this study.

PMID- 22639686
TI  - The economic divide in outcome following severe head injury.
AB  - BACKGROUND: Socioeconomic status is an important determinant of the standard of
      living and health status of people. OBJECTIVES: To assess the influence of
      economic status on the outcome following severe head injury. MATERIALS AND
      METHODS: Adult patients of severe head injury, whose guardians' volunteered
      information on family income, were enrolled for the study. The family per capita
      income was then calculated. They were studied prospectively in relation to
      various factors and followed-up. RESULTS: Among 99 patients, monthly per capita
      income of Rs. <500, 500-1000, 1000-2000, and >2000 were noted in 20, 43, 22, and
      14 patients, respectively. The credibility of information on income was confirmed
      by positive correlation with patients' mid arm circumference measurements
      (P<0.001). They were divided into two groups (family monthly per capita income
      <=Rs.1000 and >Rs.1000). The comparability of both groups based on age, Glasgow
      Coma Scale, systemic injury, and surgical intervention was confirmed (P>0.05).
      Mortality at one month was 49% among patients whose monthly per capita income
      <=Rs.1000 compared with 17% of the rest (Odds ratio [OR] 4.0, P=0.003).
      Unfavorable outcome at three months was noted in 63% of patients whose monthly
      per capita income <=Rs.1000, as compared with 35% of those with per capita income
      >Rs.1000 (OR 4.1, P=0.01). In multivariate analysis, family monthly per capita
      income <=Rs.1000 emerged as an independent risk factor for unfavorable outcome at
      three months (P=0.02). CONCLUSION: In patients of severe head injury, lower
      economic status is significantly associated with unfavorable outcome at three
      months, independent of other factors.

PMID- 22639687
TI  - Pterional approach versus unilateral frontal approach on tuberculum sellae
      meningioma: Single centre experiences.
AB  - INTRODUCTION: Tuberculum Sellae Meningioma is one of the most challenging
      surgeries among neurosurgeons. Many approaches have been established in the
      effort of removing the tumor and some of them are supported by an advanced
      neurosurgical technology. In this study, we aim to compare the efficacy of the
      two most common approaches, the pterional and the unilateral frontal. MATERIALS
      AND METHODS: This was a restrospective study that aimed to observe the efficacy
      of the two most common approaches used in our center, the pterional and the
      unilateral frontal, in resecting the tuberculum sellae meningioma, which was held
      in Dr. Hasan Sadikin General Hospital, Bandung, from July 2007-July 2010. Twenty
      patients were enrolled with half of them operated by the pterional approach and
      the rest by unilateral frontal approach. We evaluated six parameters: tumor size,
      degree of tumor removal, surgery duration, post-operative cerebral edema,
      patients' outcome, and length of stay, which were evaluated to take measure of
      the efficacy of each procedure. RESULTS: We found that the pterional approach
      gave more advantages than the unilateral frontal. Total tumor removal, especially
      in tumor size >= 3 cm was achieved in a greater number of subjects in the
      pterional (P<0.023). Other advantages of the pterional compared to the unilateral
      frontal were a shorter surgical duration (P=0.024), shorter length of stay
      (P=0.009) and less frequency of post-operative cerebral edema incidence
      (P=0.023). CONCLUSION: According to our facilities and conditions, it seems that
      the pterional approach have more advantages than the unilateral frontal approach
      in tuberculum sellae meningioma surgery.

PMID- 22639688
TI  - Role of conventional lumbar myelography in the management of sciatica: An
      experience from Pakistan.
AB  - OBJECTIVES: A prospective study of 80 patients suffering from sciatica was
      conducted at Fauji Foundation Hospital, Rawalpindi, Pakistan. The aim of this
      study was to select patients for lumbar myelography on clinical grounds in the
      absence of magnetic resonance imaging (MRI)/computerized tomography (CT)
      facilities and to know the causes of sciatica. MATERIALS AND METHODS: All
      patients underwent conventional lumbar myelography due to lack of MRI facility at
      a local hospital as well as financial constraints. Myelography was done with
      radio-opaque dye, Iopamidol, on outpatient basis RESULTS: Lumbar myelograms were
      positive in 77.5% and negative in 22.5% cases. Minor complications in the form of
      headache developed in 32.5% patients but no major complication like meningitis
      and archnoiditis developed. Lumbar disc prolapse and stenosis were found to be
      common causes of sciatica. Non-filling of nerve roots was seen in 33.87%, blocks
      (complete/partial) in 54.83%, and stenosis in 11.29% patients. CONCLUSIONS:
      Conventional myelography was found to be safe and an informative diagnostic
      technique in areas where facility of high-tech investigations like CT/MRI was not
      available. Conventional lumbar myelography could be recommended and performed
      with confidence on outdoor basis, in cases of sciatica with positive straight leg
      raising test, reflex loss, sensory, or motor deficit.

PMID- 22639689
TI  - Anaplastic hemangiopericytoma manifesting as a rapidly enlarging extracranial
      mass lesion.
AB  - We, herein, present a patient with a recurrent anaplastic hemanigiopericytoma
      manifesting as a rapidly enlarging extracranial mass lesion, which was revealed
      by pathological and intraoperative findings. In practice, this case highlights
      the mandatory need for a careful long-term follow-up for patients with
      hemangiopericytoma, since recurrence with a greater degree of malignancy can
      develop following an extended disease-free interval, as such knowledge will be
      helpful for planning the optimal surgical procedures.

PMID- 22639690
TI  - Dorsal root entry zone approach in ventral and eccentric intramedullary tumors: A
      report of 2 cases.
AB  - Intramedullary tumors constitute 2-4% of all the tumors affecting the central
      nervous system. They include low-grade astrocytomas and ependymomas in majority.
      Earlier, only biopsy or decompression used to be the best available options for
      these tumors, but with the upcoming technology and newer techniques, gross total
      excision with the aim of achieving complete removal has been the preferred
      treatment for these tumors. Usually, nearly all intramedullary tumors are
      approached from posterior midline myelotomy as this is the safest corridor to
      approach under neurophysiologic monitoring. But sometimes, if the tumor is
      exophytic, eccentric, or ventral to the cord, other routes of access may also be
      useful. These approaches are less frequently used these days and actually may be
      found useful in certain cases. Hence, they should not be termed "obsolete" and
      must be kept in mind for tumors in specific location. We describe a similar less
      commonly used dorsal root entry zone approach for near total excision of ventral
      and eccentric cervical pilocytic astrocytomas in two patients.

PMID- 22639691
TI  - Primary glioblastoma multiforme of medulla oblongata: Case report and review of
      literature.
AB  - Glioblastoma multiforme (GBM) is the most common glial tumor of the adult brain.
      However, the primary GBM of medulla oblongata is a rarity. To the best of our
      knowledge, only four cases of GBM of medulla oblongata have been reported so far
      in the literature, and this is the second report of conventional GBM of the
      medulla oblongata in adults. We describe a case of 51-year-old female, who
      presented with a heterogeneous mass with exophytic feature located in the caudal
      brain stem that was approached and a near total tumor removal was achieved by
      median suboccipital route. A literature review with emphasis on anatomical
      location, radiological and histopathological findings, extent of tumor
      resectibility, and outcome is included.

PMID- 22639692
TI  - Giant non-traumatic arteriovenous malformation of the scalp.
AB  - Arteriovenous malformation (AVM) of the scalp is an uncommon entity. Its
      management is difficult because of its high shunt flow, complex vascular anatomy,
      and possible cosmetic complications. The etiology of scalp AVMs may be
      spontaneous or traumatic. Clinical symptoms frequently include pulsatile mass,
      headache, local pain, tinnitus; and less frequently, hemorrhage and necrosis.
      Selective angiography is the most significant diagnosis method. Surgical excision
      is especially effective in AVMs and the most frequently used treatment method. In
      this article, we discussed the clinical features and surgical management of scalp
      AVMs.

PMID- 22639693
TI  - Intra-axial CNS dermoid cyst.
AB  - Intracranial dermoid cysts are rare tumors. They constitute 0.3% of intracranial
      tumors. These are commonly seen in the midline and sylvian area. Intraaxial
      lesions are extremely rare. We report the case of a 35-years-old female with a
      large intraaxial dermoid cyst, which was reported as oligodendroglioma on imaging
      studies done preoperatively, but was confirmed to be a dermoid cyst intra
      operatively and on histopathological examination; thus highlighting a diagnostic
      dilemma. Patient did well post operatively and there is no recurrence in the one
      year follow-up. To conclude, dermoid cysts are rare benign tumors, and intraaxial
      lesions are still rarer. Complete surgical excision may become difficult due to
      adherence to nerves and vessels.

PMID- 22639694
TI  - Hypoparathyrodism.

PMID- 22639695
TI  - Limited unilateral partial laminectomy and lateral dural incision: One of the
      best approaches for spinal meningioma in selected cases.

PMID- 22639696
TI  - Impact of physical activity on activity of daily living in moderate to severe
      dementia: a critical review.
AB  - The objectives of this study were to describe the different modalities of
      physical activity programs designed for moderate to severe dementia and to
      identify their impact on functional independence in activities of daily living
      (ADL). A critical review of randomized controlled trials related to the impact of
      physical activity programs in moderately to severely demented persons on ADL
      performance and meta-analysis of the identified studies were performed. Among the
      303 identified articles, five responded to the selection criteria. Four out of
      the five studies demonstrated limited methodological quality. In one high-quality
      study, physical activity programs significantly delayed deterioration of ADL
      performance. The program components and ADL assessment tools vary widely across
      studies. Although the proposed treatments have not proven their efficiency in
      improving the ADL status of the patients, they were able to limit the decline in
      ADL functioning. Future research is warranted in order to identify clinically
      relevant modalities for physical activity programs for people with moderate to
      severe dementia.

PMID- 22639697
TI  - The Modified Depression Scale (MDS): A Brief, No-Cost Assessment Tool to Estimate
      the Level of Depressive Symptoms in Students and Schools.
AB  - Adolescent health researchers and practitioners are frequently interested in
      assessing depression as part of student screening and for school-wide prevention
      and intervention planning. However, this task is challenging given the lack of
      free, brief assessments of depressive symptoms in youth. This study evaluated the
      psychometric properties of an adapted version of the Modified Depression Scale
      (MDS). Data came from a school-based survey of 9th-12th graders in Boston
      (N=1,657). We assessed internal consistency reliability and known-groups
      validity, in addition to the feasibility of establishing a dichotomous cut-point
      to classify adolescents as having high versus low depressive symptoms. We also
      evaluated the validity of the adapted MDS as a school-wide measure. At the
      student-level, the adapted MDS demonstrated acceptable internal consistency.
      Students engaging in risk behaviors (e.g., substance use) or who were victimized
      (e.g., bullied) had significantly higher depressive symptom scores. Students who
      endorsed four or five MDS symptoms often or always had a heightened risk of
      suicidal ideation, substance use, and failing grades when compared to students
      who endorsed three or fewer symptoms often or always. At the school-level, higher
      mean levels of depressive symptoms in a school were associated with higher mean
      levels of suicidal ideation and failing grades. Results of this study suggest
      that the adapted MDS is a promising measurement tool that could be useful to
      school-based professionals and researchers to evaluate depressive symptoms in
      adolescents and ascertain the prevalence of depressive symptoms in schools.

PMID- 22639698
TI  - Von Willebrand Factor permeates small vessels in CADASIL and inhibits smooth
      muscle gene expression.
AB  - BACKGROUND AND PURPOSE: CADASIL (cerebral autosomal dominant arteriopathy
      subcortical infarcts and leukoencephalopathy) is a genetic disorder hallmarked by
      ischemic stroke and vascular dementia. Characteristic pathological changes in the
      vasculature include thickening of small arteries and accumulation of
      heterogeneous material within the vessel wall. We tested whether endothelial von
      Willebrand factor (vWF) accumulates in CADASIL vessels and whether exposure of
      smooth muscle cells to vWF alters the expression of smooth muscle gene
      expression. METHODS: Brain sections obtained at autopsy from six North American
      CADASIL patients were examined using immunohistochemistry for vWF and IgG. Rat
      aortic smooth muscle cells (A7R5 cells) were tested for binding to infrared-tag
      labeled vWF. Finally, A7R5 cells were exposed to vWF, and expression of mature
      smooth muscle marker genes was analyzed by quantitative reverse transcriptase
      PCR. RESULTS: vWF is expressed in the penetrating arterial walls in all CADASIL
      samples. IgG, a marker of serum extravasation, was present only in a minority of
      arterial walls. vWF binds to smooth muscle cells in vitro, and low concentrations
      of vWF rapidly activate c-fos, EGR, TSP1, and c-myc while specifically inhibiting
      RNA encoding smooth muscle actin, calponin, and SM22. CONCLUSIONS: These data
      demonstrate that vWF, likely produced by the endothelium, permeates the vessel
      wall of CADASIL brains. Exposure of smooth muscle cells to vWF results in
      reduction of specific RNAs required for normal vascular homeostasis. This is the
      first report of accumulation of a protein within CADASIL vessels that inhibits
      vascular gene expression and implicates a role for vWF beyond hemostasis.

PMID- 22639699
TI  - Embryonic stem cells: protein interaction networks.
AB  - Embryonic stem cells have the ability to differentiate into nearly all cell
      types. However, the molecular mechanism of its pluripotency is still unclear.
      Oct3/4, Sox2 and Nanog are important factors of pluripotency. Oct3/4 (hereafter
      referred to as Oct4), in particular, has been an irreplaceable factor in the
      induction of pluripotency in adult cells. Proteins interacting with Oct4 and
      Nanog have been identified via affinity purification and mass spectrometry. These
      data, together with iterative purifications of interacting proteins allowed a
      protein interaction network to be constructed. The network currently includes 77
      transcription factors, all of which are interconnected in one network. In-depth
      studies of some of these transcription factors show that they all recruit the
      NuRD complex. Hence, transcription factor clustering and chromosomal remodeling
      are key mechanism used by embryonic stem cells. Studies using RNA interference
      suggest that more pluripotency genes are yet to be discovered via protein-protein
      interactions. More work is required to complete and curate the embryonic stem
      cell protein interaction network. Analysis of a saturated protein interaction
      network by system biology tools can greatly aid in the understanding of the
      embryonic stem cell pluripotency network.

PMID- 22639700
TI  - Mitochondrial DNA: A Blind Spot in Neuroepigenetics.
AB  - Neuroepigenetics, which includes nuclear DNA modifications such as 5
      methylcytosine and 5-hydoxymethylcytosine and modifications of nuclear proteins
      such as histones, is emerging as the leading field in molecular neuroscience.
      Historically, a functional role for epigenetic mechanisms, including in
      neuroepigenetics, has been sought in the area of the regulation of nuclear
      transcription. However, one important compartment of mammalian cell DNA,
      different from nuclear but equally important for physiological and pathological
      processes (including in the brain), mitochondrial DNA has for the most part not
      had a systematic epigenetic characterization. The importance of mitochondria and
      mitochondrial DNA (particularly its mutations) in central nervous system
      physiology and pathology has long been recognized. Only recently have mechanisms
      of mitochondrial DNA methylation and hydroxymethylation, including the discovery
      of mitochondrial DNA-methyltransferases and the presence and the functionality of
      5-methylcytosine and 5-hydroxymethylcytosine in mitochondrial DNA (e.g., in
      modifying the transcription of mitochondrial genome), been unequivocally
      recognized as a part of mammalian mitochondrial physiology. Here we summarize for
      the first time evidence supporting the existence of these mechanisms and we
      propose the term "mitochondrial epigenetics" to be used when referring to them.
      Currently, neuroepigenetics does not include mitochondrial epigenetics - a gap
      that we expect to close in the near future.

PMID- 22639701
TI  - ESTIMATING WITHIN-SCHOOL CONTACT NETWORKS TO UNDERSTAND INFLUENZA TRANSMISSION.
AB  - Many epidemic models approximate social contact behavior by assuming random
      mixing within mixing groups (e.g., homes, schools, and workplaces). The effect of
      more realistic social network structure on estimates of epidemic parameters is an
      open area of exploration. We develop a detailed statistical model to estimate the
      social contact network within a high school using friendship network data and a
      survey of contact behavior. Our contact network model includes classroom
      structure, longer durations of contacts to friends than non-friends and more
      frequent contacts with friends, based on reports in the contact survey. We
      performed simulation studies to explore which network structures are relevant to
      influenza transmission. These studies yield two key findings. First, we found
      that the friendship network structure important to the transmission process can
      be adequately represented by a dyad-independent exponential random graph model
      (ERGM). This means that individual-level sampled data is sufficient to
      characterize the entire friendship network. Second, we found that contact
      behavior was adequately represented by a static rather than dynamic contact
      network. We then compare a targeted antiviral prophylaxis intervention strategy
      and a grade closure intervention strategy under random mixing and network-based
      mixing. We find that random mixing overestimates the effect of targeted antiviral
      prophylaxis on the probability of an epidemic when the probability of
      transmission in 10 minutes of contact is less than 0.004 and underestimates it
      when this transmission probability is greater than 0.004. We found the same
      pattern for the final size of an epidemic, with a threshold transmission
      probability of 0.005. We also find random mixing overestimates the effect of a
      grade closure intervention on the probability of an epidemic and final size for
      all transmission probabilities. Our findings have implications for policy
      recommendations based on models assuming random mixing, and can inform further
      development of network-based models.

PMID- 22639702
TI  - Structured penalties for functional linear models-partially empirical
      eigenvectors for regression.
AB  - One of the challenges with functional data is incorporating geometric structure,
      or local correlation, into the analysis. This structure is inherent in the output
      from an increasing number of biomedical technologies, and a functional linear
      model is often used to estimate the relationship between the predictor functions
      and scalar responses. Common approaches to the problem of estimating a
      coefficient function typically involve two stages: regularization and estimation.
      Regularization is usually done via dimension reduction, projecting onto a
      predefined span of basis functions or a reduced set of eigenvectors (principal
      components). In contrast, we present a unified approach that directly
      incorporates geometric structure into the estimation process by exploiting the
      joint eigenproperties of the predictors and a linear penalty operator. In this
      sense, the components in the regression are 'partially empirical' and the
      framework is provided by the generalized singular value decomposition (GSVD). The
      form of the penalized estimation is not new, but the GSVD clarifies the process
      and informs the choice of penalty by making explicit the joint influence of the
      penalty and predictors on the bias, variance and performance of the estimated
      coefficient function. Laboratory spectroscopy data and simulations are used to
      illustrate the concepts.

PMID- 22639703
TI  - Enhancing the intelligibility of high intensity speech: Evidence of inhibition in
      the lower auditory pathway.
AB  - Intelligibility of narrowband speech declines considerably at high intensities,
      but substantial recovery from this "rollover" occurs when flanking noise bands
      are added. The present study employed two types of added noise: narrowband noise
      matching the spectral limits of the rectangular speech band (producing within
      band masking) versus broadband noise (producing within band masking plus
      simultaneous enhancement by out of band noise components). When noise added to
      diotic speech in experiment 1 was interaurally uncorrelated rather than diotic,
      intelligibility increased 5%, regardless of noise bandwidth. Interestingly,
      regardless of interaural correlation, intelligibility was 13% higher with
      broadband rather than narrowband noise, indicating that noise induced recovery
      from rollover precedes binaural processing. In experiment 2, diotic noise was
      presented either continuously or gated on and off with individual sentences.
      Intelligibility was 5% higher with continuous noise, showing adaptation of
      masking, which occurred regardless of noise bandwidth. Moreover, intelligibility
      was about 11% higher with broadband rather than narrowband noise, regardless of
      gating, ruling out peripheral adaptation as a source of recovery from rollover.
      These and other findings discussed are consistent with previous suggestions that
      intelligibility at high intensities is preserved by inhibition of rate-saturated
      auditory nerve input to secondary neurons of the cochlear nucleus.

PMID- 22639704
TI  - alpha-Ketoheterocycle-based Inhibitors of Fatty Acid Amide Hydrolase (FAAH).
AB  - A summary of the initial discovery and characterization of the enzyme fatty acid
      amide hydrolase (FAAH), and the subsequent advancement of an important class of
      competitive, reversible, potent and selective inhibitors is presented. Initially
      explored using substrate-inspired inhibitors bearing electrophilic carbonyls, the
      examination of alpha-ketoheterocyle-based inhibitors of FAAH with the benefit of
      a unique activity-based protein-profiling (ABPP)-based proteome-wide selectivity
      assay, a powerful in vivo biomarker-based in vivo screen, and subsequent
      retrospective X-ray co-crystal structures with the enzyme, is summarized. These
      efforts defined the impact of the central activating heterocycle and its key
      substituents, provided key simplifications in the C2 acyl side chain and clear
      interpretations for the unique role and subsequent optimization of the central
      activating heterocycle, and established the basis for the recent further
      conformational constraints in the C2 acyl side chain, providing potent, long
      acting, orally-active FAAH inhibitors.

PMID- 22639705
TI  - Substance Abuse Treatment Stage and Personal Networks of Women in Substance Abuse
      Treatment.
AB  - This study examines the relationship among 4 treatment stages (i.e., engagement,
      persuasion, active treatment, relapse prevention) and the composition, social
      support, and structural characteristics of personal networks. The study sample
      includes 242 women diagnosed with substance dependence who were interviewed
      within their first month of intensive outpatient treatment. Using EgoNet
      software, the women reported on their 25 alter personal networks and the
      characteristics of each alter. With one exception, few differences were found in
      the network compositions at different stages of substance abuse treatment. The
      exception was the network composition of women in the active treatment stage,
      which included more network members from treatment programs or 12-Step meetings.
      Although neither the type nor amount of social support differed across treatment
      stages, reciprocity differed between women in active treatment and those in the
      engagement stage. Networks of women in active treatment were less connected, as
      indicated by a higher number of components, whereas networks of women in the
      persuasion stage had a higher degree of centralization, as indicated by networks
      dominated by people with the most ties. Overall, we find social network
      structural variables to relate to the stage of treatment, whereas network
      composition, type of social support, and sociodemographic variables (with a few
      exceptions) do not relate to treatment stage. Results suggest that social
      context, particularly how social contacts are arranged around clients, should be
      incorporated into treatment programs, regardless of demographic background.

PMID- 22639706
TI  - Breadth of knowledge vs. grades: What best predicts achievement in the first year
      of health sciences programmes?
AB  - This study aimed to identify those features within secondary school curricula and
      assessment, particularly science subjects that best predict academic achievement
      in the first year of three different three-year undergraduate health professional
      programmes (nursing, pharmacy, and health sciences) at a large New Zealand
      university. In particular, this study compared the contribution of breadth of
      knowledge (number of credits acquired) versus grade level (grade point average)
      and explored the impact of demographic variables on achievement. The findings
      indicated that grades are the most important factor predicting student success in
      the first year of university. Although taking biology and physics at secondary
      school has some impact on university first year achievement, the effect is
      relatively minor.

PMID- 22639707
TI  - Analysis of prognostic factors relating to postoperative survival in spinal
      metastases.
AB  - OBJECTIVE: To analyze the prognostic factors thought to be related with survival
      time after a spinal metastasis operation. METHODS: We retrospectively analyzed
      217 patients who underwent spinal metastasis operations in our hospital from 2001
      to 2009. Hematological malignancies, such as multiple myeloma and lymphoma, were
      excluded. The factors thought to be related with postoperative survival time were
      gender, age (below 55, above 56), primary tumor growth rate (slow, moderate,
      rapid group), spinal location (cervical, thoracic, and lumbo-sacral spine), the
      timing of radiation therapy (preoperative, postoperative, no radiation),
      operation type (decompressive laminectomy with or without posterior fixation,
      corpectomy with anterior fusion, corpectomy with posterior fixation),
      preoperative systemic condition (below 5 points, above 6 points classified by
      Tomita scoring), pre- and postoperative ambulatory function (ambulatory, non
      ambulatory), number of spinal metastases (single, multiple), time to spinal
      metastasis from the primary cancer diagnosis (below 21 months, above 22 months),
      and postoperative complication. RESULTS: The study cohort mean age at the time of
      surgery was 55.5 years. The median survival time after spinal operation and
      spinal metastasis diagnosis were 6.0 and 9.0 months. In univariate analysis,
      factors such as gender, primary tumor growth rate, preoperative systemic
      condition, and preoperative and postoperative ambulatory status were shown to be
      related to postoperative survival. In multivariate analysis, statistically
      significant factors were preoperative systemic condition (p=0.048) and
      postoperative ambulatory status (p<0.001). The other factors had no statistical
      significance. CONCLUSION: The factors predictive for postoperative survival time
      should be considered in the surgery of spinal metastasis patients.

PMID- 22639709
TI  - Intramedullary spinal cord metastasis of choriocarcinoma.
AB  - The authors describe a case of choriocarcinoma that metastasized to the cerebral
      cortex, vertebral body, and intramedullary spinal cord. A 21-year-old woman
      presented with sudden headache, vomiting and a visual field defect. Brain
      computed tomography and magnetic resonance examinations revealed an intracranial
      hemorrhage in the left temporo-parietal lobe and two enhancing nodules in the
      left temporal and right frontal lobe. After several days, the size of the
      hemorrhage increased, and a new hemorrhage was identified in the right frontal
      lobe. The hematoma and enhancing mass in the left temporo-parietal lobe were
      surgically removed. Choriocarcinoma was diagnosed after histological examination.
      At 6 days after the operation, her consciousness had worsened and she was in a
      state of stupor. The size of the hematoma in the right frontal lobe was enlarged.
      We performed an emergency operation to remove the hematoma and enhancing mass.
      Her mental status recovered slowly. Two months thereafter, she complained of
      paraplegia with sensory loss below the nipples. Whole spine magnetic resonance
      imaging revealed a well-enhancing mass in the thoracic intramedullary spinal cord
      and L2 vertebral body. Despite chemotherapy and radiotherapy, the patient died 13
      months after the diagnosis.

PMID- 22639708
TI  - Radiographic Comparison of Four Anterior Fusion Methods in Two Level Cervical
      Disc Diseases : Autograft Plate Fixation versus Cage Plate Fixation versus Stand
      Alone Cage Fusion versus Corpectomy and Plate Fixation.
AB  - OBJECTIVE: To evaluate radiographic results of anterior fusion methods in two
      level cervical disc disease : tricortical autograft and plate fixation (ACDF-AP),
      cage and plate fixation (ACDF-CP), stand-alone cage (ACDF-CA), and corpectomy and
      plate fixation (ACCF). METHODS: The numbers of patients were 70 with a minimum 6
      month follow-up (ACDF-AP : 12, ACDF-CP : 27, ACDF-CA : 15, and ACCF : 16).
      Dynamic simple X-ray and computed tomography were evaluated preoperatively,
      postoperatively, 6 month, and at the final follow-up. The fusion and subsidence
      rates at the final were determined, and global cervical lordosis (GCL), cervical
      range of motion, fused segment angle (FSA), and fused segment height (FSH) were
      analyzed. RESULTS: Nonunion was observed in 4 (25%) patients with ACDF-CA, 1 (8%)
      patient with ACDF-AP, 1 (4%) patient with ACDF-CP. The number of loss of FSH (%)
      more than 3 mm were 2 patients (16%) in ACDF-AP, 3 patients (11%) in ACDF-CP, 5
      patients (33%) in ACDF-CA, and 3 patients (20%) in ACCF. The GCL was decreased
      with ACDF-CA and increased with others. The FSA was increased with ACDF-AP, ACDF
      CP, and ACCF, but ACDF-CA was decreased. At the final follow-up, the FSH was
      slightly decreased in ACDF-CP, ACDF-AP, and ACCF, but ACDF-CA was more decreased.
      Graft related complication were minimal. Screw loosening, plate fracture, cage
      subsidence and migration were not identified. CONCLUSION: ACDF-CP demonstrated a
      higher fusion rate and less minimal FSH loss than the other fusions in two-level
      cervical disc disease. The ACDF-AP and ACCF methods had a better outcome than the
      ACDF-CA with respect to GCL, FSA, and FSH.

PMID- 22639710
TI  - Astrocytoma in the third ventricle and hypothalamus presenting with parkinsonism.
AB  - Parkinsonism secondary to intracranial mass lesions usually results from
      compression or distortion of the basal ganglia. Secondary parkinsonism due to
      midbrain infiltration or compression is rare and generally associated with other
      neurologic signs caused by pyramidal tract and/or cranial nerve involvement. We
      report a case of 30-year-old woman in whom mild parkinsonism was the major
      clinical manifestation of an astrocytoma in the anterior third ventricle and
      hypothalamus. She underwent surgical resection, ventriculoperitoneal shunt and
      radiation therapy. All symptoms of parkinsonism were completely recovered 3
      months after the treatment. Brain tumors can be manifested only by the symptoms
      of parkinsonism. This case emphasizes the significance of neuroimaging in the
      evaluation of parkinsonism.

PMID- 22639711
TI  - Extraneural metastasis of glioblastoma multiforme presenting as an unusual neck
      mass.
AB  - Glioblastoma multiforme (GBM) is the most aggressive intracranial tumor and it
      commonly spreads by direct extension and infiltration into the adjacent brain
      tissue and along the white matter tract. The metastatic spread of GBM outside of
      the central nervous system (CNS) is rare. The possible mechanisms of extraneural
      metastasis of the GBM have been suggested. They include the lymphatic spread, the
      venous invasion and the direct invasion through dura and bone. We experienced a
      46-year-old man who had extraneural metastasis of the GBM on his left neck. The
      patient was treated with surgery for 5 times, radiotherapy and chemotherapy. He
      had survived 6 years since first diagnosed. Although the exact mechanism of the
      extraneural metastasis is not well understood, this present case shows the
      possibility of extraneural metastasis of the GBM, especially in patients with
      long survival.

PMID- 22639712
TI  - Two cases of primary osteolytic intraosseous meningioma of the skull
      metastasizing to whole skull and the spine.
AB  - We report here two cases of primary intraosseous meningioma with aggressive
      behavior. A 68-year-old man presented with a one year history of a soft,
      enlarging mass in the right parietal region. Magnetic resonance image (MRI)
      revealed a 6 cm sized, heterogeneously-enhancing, bony expansile mass in the
      right parietal bone, and computed tomograph (CT) showed a bony, destructive
      lesion. The tumor, including the surrounding normal bone, was totally resected.
      Dural invasion was not apparent. Diagnosis was atypical meningioma, which
      extensively metastasized within the skull one year later. A 74-year-old woman
      presented with a 5-month history of a soft mass on the left frontal area. MRI
      revealed a 4 cm sized, multilobulated, strongly-enhancing lesion on the left
      frontal bone, and CT showed a destructive lesion. The mass was adhered tightly to
      the scalp and dura mater. The lesion was totally removed. Biopsy showed a
      papillary meningioma. The patient refused adjuvant radiation therapy and later
      underwent two reoperations for recurred lesions, at 19 and at 45 months
      postoperative. The patient experienced back pain 5 years later, and MRI showed an
      osteolytic lesion on the 11th thoracic vertebra. After her operation, a
      metastatic papillary meningioma was diagnosed. These osteolytic intraosseous
      meningiomas had atypical/malignant pathologies, which metastasized to whole skull
      and the spine.

PMID- 22639713
TI  - Bilateral vertebral artery dissecting aneurysms presenting with subarachnoid
      hemorrhage treated by staged coil trapping and covered stents graft.
AB  - The treatment of bilateral vertebral artery dissecting aneurysms (VADAs)
      presenting with subarachnoid hemorrhage (SAH) is still challenging. The authors
      report a rare case of bilateral VADA treated with coil trapping of ruptured VADA
      and covered stents implantation after multiple unsuccessful stent assisted
      coiling of the contralateral unruptured VADA. A 44-year-old woman was admitted to
      our hospital because of severe headache and sudden stuporous consciousness. Brain
      CT showed thick SAH and intraventricular hemorrhage. Cerebral angiography
      demonstrated bilateral VADA. Based on the SAH pattern and aneurysm
      configurations, the right VADA was considered ruptured. This was trapped with
      endovascular coils without difficulty. One month later, the contralateral
      unruptured VADA was protected using a stent-within-a-stent technique, but marked
      enlargement of the left VADA was detected by 8-months follow-up angiography.
      Subsequently two times coil packing for pseudosacs resulted in near complete
      occlusion of left VADA. However, it continued to grow. Covered stents graft below
      the posterior inferior cerebellar artery (PICA) origin and a coronary stent
      implantation across the origin of the PICA resulted in near complete obliteration
      of the VADA. Covered stent graft can be used as a last therapeutic option for the
      management of VADA, which requires absolute preservation of VA flow.

PMID- 22639714
TI  - A case of lateral medullary infarction after endovascular trapping of the
      vertebral artery dissecting aneurysm.
AB  - We report an unusual case of lateral medullary infarction after successful
      embolization of the vertebral artery dissecting aneurysm (VADA). A 49-year-old
      man who had no noteworthy previous medical history was admitted to our hospital
      with a severe headache. Computed tomography (CT) revealed a subarachnoid
      hemorrhage, located in the basal cistern and posterior fossa. Cerebral
      angiography showed a VADA, that did not involve the origin of the posterior
      inferior cerebellar artery (PICA). We treated this aneurysm via endovascular
      trapping of the vertebral artery distal to the PICA. After operation, CT revealed
      post-hemorrhagic hydrocephalus, which we resolved with a permanent
      ventriculoperitoneal shunt procedure. Postoperatively, the patient experienced
      transient mild hoarsness and dysphagia. Magnetic resonance image (MRI) showed a
      small infarction in the right side of the medulla. The patient recovered well,
      though he still had some residual symptom of dysphagia at discharge. Such an
      event is uncommon but can be a major clinical concern. Further investigation to
      reveal risk factors and/or causative mechanisms for the medullary infarction
      after successful endovascular trapping of the VADA are sorely needed, to minimize
      such a complication.

PMID- 22639716
TI  - Mysterious foreign body in transverse sinus.
AB  - This case report describes a patient who had a foreign body in transverse sinus.
      A 35-year-old Korean-Chinese man visited the emergency room with lacerated wound
      in left eyelid and a foreign body which was stumbled upon in the skull. On
      examination, there was right side hemianopsia in his left eye. He did not
      complain any headache or show any abnormal neurological signs, but there was a
      foreign body at left transverse sinus in computed tomography which was taken at
      another hospital. There was no intracranial abnormality except the foreign body
      in computed tomography. Because of the financial problem, additional evaluations
      were not possible. We herein report a strange case in which the pathway of a
      foreign body to locate in transverse sinus was ambiguous, and suggest that the
      foreign body located in transverse sinus might have been the penetrated along the
      anterior fontanelle and passed through the superior sagittal sinus.

PMID- 22639715
TI  - Gunshot injury to the anterior arch of atlas.
AB  - Penetrating injuries to the upper cervical spine resulting from gunshots are rare
      in South Korea due to restrictions of gun use. Moreover, gunshot wounds to the
      upper cervical spine without neurological deficits occur infrequently because of
      the anatomic location and surrounding essential structures. We present an
      uncommon case involving the surgical removal of a bullet located in the anterior
      arch of first cervical vertebra (C1) via a transoral approach without
      neurological complications or subsequent mechanical instability.

PMID- 22639717
TI  - Migration of sparganosis from the brain to the cervical spinal cord.
AB  - Central nervous system (CNS) sparganosis is a rare parasitic infestation caused
      by ingestion of the raw or inadequately cooked snakes or frogs. Sparganum is well
      known for its ability of migrating though the tissue, therefore, it can cause
      various neurological symptoms if it involves neurological systems. A 51-year-old
      male patient visited our department of neurosurgery complaining of the motor
      weakness and radiating pain on both upper extremities over 4 months. He had a
      history of ingesting raw snakes untill his late twenties. The magnetic resonance
      (MR) images of cervical spine revealed an intramedullary ill-defined enhancing
      lesion with the aggregated cysts in the upper cervical spinal cord. Under
      presumptive diagnosis of sparganosis, we took brain MR image. The brain MR images
      revealed the signal change in right fronto-temporal lobe suggesting the
      trajectory of parasitic migration via ventricular systems. He underwent a midline
      myelotomy and granuloma removal followed by the posterior laminoplasty.
      Pathologic findings showed inflammatory changes and necrosis with keratinized
      tissue suggesting the CNS sparganosis. We report an uncommon case of CNS
      sparganosis migrated from the brain to the spinal cord with literature review.

PMID- 22639718
TI  - An acute postoperative intractable hyperventilation after an endoscopic third
      ventriculostomy.
AB  - This report describes a rare case of postoperative hyperventilation attack after
      an endoscopic third ventriculostomy in a 46-year-old woman. About 60 min after
      the termination of the operation, an intractable hyperventilation started with
      respiratory rate of 65 breaths/min and EtCO(2), 16.3 mm Hg. Sedation with
      benzodiazepine, thiopental sodium, fentanyl, and propofol/remifentanil infusion
      was tried under a rebreathing mask at a 4 L/min of oxygen. With aggressive
      sedative challenges, ventilation pattern was gradually returned to normal during
      the 22 hrs of time after the surgery. A central neurogenic hyperventilation was
      suspected due to the stimulating central respiratory center by cold acidic
      irrigation solution during the neuroendoscopic procedure.

PMID- 22639719
TI  - Intraoperative vertebral artery angiography to guide c1-2 transarticular screw
      fixation in a patient with athetoid cerebral palsy.
AB  - We present a case of an athetoid cerebral palsy with quadriparesis caused by
      kyphotic deformity of the cervical spine, severe spinal stenosis at the
      cervicomedullary junction, and atlantoaxial instability. The patient improved
      after the first surgery, which included a C1 total laminectomy and C-arm guided
      righ side unilateral C1-2 transarticular screw fixation. C1-2 fixation was not
      performed on the other side because of an aberrant and dominant vertebral artery
      (VA). Eight months after the first operation, the patient required revision
      surgery for persistent neck pain and screw malposition. We used intraoperative VA
      angiography with simultaneous fluoroscopy for precise image guidance during
      bilateral C1-2 transarticular screw fixation. Intraoperative VA angiography
      allowed the accurate insertion of screws, and can therefore be used to avoid VA
      injury during C1-2 transarticular screw fixation in comorbid patients with
      atlantoaxial deformities.

PMID- 22639720
TI  - The obturator guiding technique in percutaneous endoscopic lumbar discectomy.
AB  - In conventional percutaneous disc surgery, introducing instruments into disc
      space starts by inserting a guide needle into the triangular working zone.
      However, landing the guide needle tip on the annular window is a challenging step
      in endoscopic discectomy. Surgeons tend to repeat the needling procedure to reach
      an optimal position on the annular target. Obturator guiding technique is a
      modification of standard endoscopic lumbar discectomy, in which, obturator is
      used to access triangular working zone instead of a guide needle. Obturator
      guiding technique provides more vivid feedback and easy manipulation. This
      technique decreases the steps of inserting instruments and takes safer route from
      the peritoneum.

PMID- 22639721
TI  - Quinoxalinone Inhibitors of the Lectin DC-SIGN.
AB  - The C-type lectin dendritic cell-specific intercellular adhesion molecule 3
      grabbing nonintegrin (DC-SIGN) can serve as a docking site for pathogens on the
      surface of dendritic cells. Pathogen binding to DC-SIGN can have diverse
      consequences for the host. DC-SIGN can facilitate HIV-1 dissemination, but the
      interaction of Mycobacterium tuberculosis with DC-SIGN is important for host
      immunity. The ability of pathogens to target DC-SIGN provides impetus to identify
      ligands that can perturb these interactions. Here, we describe the first stable
      small molecule inhibitors of DC-SIGN. These inhibitors were derived from a
      collection of quinoxalinones, which were assembled using a tandem cross
      metathesis-hydrogenation sequence. To assess the ability of these small molecules
      to block DC-SIGN-mediated glycan adhesion and internalization, we developed a
      sensitive flow cytometry assay. Our results reveal that the quinoxalinones are
      effective inhibitors of DC-SIGN-glycan interactions. These compounds block both
      glycan binding to cells and glycan internalization. We anticipate that these non
      carbohydrate inhibitors can be used to elucidate the role of DC-SIGN in
      pathogenesis and immune function.

PMID- 22639722
TI  - Clinical outcome measures for trials in Duchenne muscular dystrophy: report from
      International Working Group meetings.
AB  - In June 2010, 25 representatives from Europe and the US met in Washington, DC,
      USA, to discuss clinical outcome measures in Duchenne muscular dystrophy (DMD) in
      the context of clinical trial design and analysis. The workshop was organized in
      response to a September 2009 European Medicines Agency meeting where a clear
      directive was given that an international consensus needs to be developed that
      provides a foundation for age-appropriate clinical outcome measures for use in
      clinical trials of emerging therapeutics for DMD. Data were presented from eight
      multicenter longitudinal datasets, representing nearly 1900 patients over a 20
      year time period. This experience confirmed the feasibility of repeated
      evaluations performed at multiple sites and addressed several core issues in drug
      development for DMD, such as the 'new' natural history in the steroidera,
      reliability and sensitivity of specific outcome measures, as well as disease
      staging and patient selection. These data form a valuable asset for academic
      investigators, pharmaceutical sponsors and regulatory agencies involved in DMD
      therapeutics. The group remains committed working together on a number of
      collaborative goals to support the therapeutics development effort in this orphan
      disease and to make these data available to stakeholders working in the field.

PMID- 22639723
TI  - A short-term in situ CO2 enrichment experiment on Heron Island (GBR).
AB  - Ocean acidification poses multiple challenges for coral reefs on molecular to
      ecological scales, yet previous experimental studies of the impact of projected
      CO2 concentrations have mostly been done in aquarium systems with corals removed
      from their natural ecosystem and placed under artificial light and seawater
      conditions. The Coral-Proto Free Ocean Carbon Enrichment System (CP-FOCE) uses a
      network of sensors to monitor conditions within each flume and maintain
      experimental pH as an offset from environmental pH using feedback control on the
      injection of low pH seawater. Carbonate chemistry conditions maintained in the 
      0.06 and -0.22 pH offset treatments were significantly different than
      environmental conditions. The results from this short-term experiment suggest
      that the CP-FOCE is an important new experimental system to study in situ impacts
      of ocean acidification on coral reef ecosystems.

PMID- 22639724
TI  - The total amounts of radioactively contaminated materials in forests in
      Fukushima, Japan.
AB  - There has been leakage of radioactive materials from the Fukushima Daiichi
      Nuclear Power Plant. A heavily contaminated area (>= 134,137Cs 1000 kBq m-2) has
      been identified in the area northwest of the plant. The majority of the land in
      the contaminated area is forest. Here we report the amounts of biomass, litter
      (small organic matter on the surface of the soil), coarse woody litter, and soil
      in the contaminated forest area. The estimated overall volume and weight were 33
      Mm3 (branches, leaves, litter, and coarse woody litter are not included) and 21
      Tg (dry matter), respectively. Our results suggest that removing litter is an
      efficient method of decontamination. However, litter is being continuously
      decomposed, and contaminated leaves will continue to fall on the soil surface for
      several years; hence, the litter should be removed promptly but continuously
      before more radioactive elements are transferred into the soil.

PMID- 22639725
TI  - Noradrenergic 'tone' determines dichotomous control of cortical spike-timing
      dependent plasticity.
AB  - Norepinephrine (NE) is widely distributed throughout the brain. It modulates
      intrinsic currents, as well as amplitude and frequency of synaptic transmission
      affecting the 'signal-to-noise ratio' of sensory responses. In the visual cortex,
      alpha1- and beta-adrenergic receptors (AR) gate opposing effects on long-term
      plasticity of excitatory transmission. Whether and how NE recruits these plastic
      mechanisms is not clear. Here, we show that NE modulates glutamatergic inputs
      with different efficacies for alpha1- and beta-AR. As a consequence, the priming
      of synapses with different NE concentrations produces dose-dependent competing
      effects that determine the temporal window of spike-timing dependent plasticity
      (STDP). While a low NE concentration leads to long-term depression (LTD) over
      broad positive and negative delays, a high NE concentration results in
      bidirectional STDP restricted to very narrow intervals. These results indicate
      that the local availability of NE, released during emotional arousal, determines
      the compound modulatory effect and the output of STDP.

PMID- 22639727
TI  - Nitrogen-limited mangrove ecosystems conserve N through dissimilatory nitrate
      reduction to ammonium.
AB  - Earlier observations in mangrove sediments of Goa, India have shown
      denitrification to be a major pathway for N loss. However, percentage of total
      nitrate transformed through complete denitrification accounted for <0-72% of the
      pore water nitrate reduced. Here, we show that up to 99% of nitrate removal in
      mangrove sediments is routed through dissimilatory nitrate reduction to ammonium
      (DNRA). The DNRA process was 2x higher at the relatively pristine site Tuvem
      compared to the anthropogenically-influenced Divar mangrove ecosystem. In systems
      receiving low extraneous nutrient inputs, this mechanism effectively conserves
      and re-circulates N minimizing nutrient loss that would otherwise occur through
      denitrification. In a global context, the occurrence of DNRA in mangroves has
      important implications for maintaining N levels and sustaining ecosystem
      productivity. For the first time, this study also highlights the significance of
      DNRA in buffering the climate by modulating the production of the greenhouse gas
      nitrous oxide.

PMID- 22639726
TI  - Excellent capability in degrading azo dyes by MgZn-based metallic glass powders.
AB  - The lack of new functional applications for metallic glasses hampers further
      development of these fascinating materials. In this letter, we report for the
      first time that the MgZn-based metallic glass powders have excellent functional
      ability in degrading azo dyes which are typical organic water pollutants. Their
      azo dye degradation efficiency is about 1000 times higher than that of commercial
      crystalline Fe powders, and 20 times higher than the Mg-Zn alloy crystalline
      counterparts. The high Zn content in the amorphous Mg-based alloy enables a
      greater corrosion resistance in water and higher reaction efficiency with azo dye
      compared to crystalline Mg. Even under complex environmental conditions, the MgZn
      based metallic glass powders retain high reaction efficiency. Our work opens up a
      new opportunity for functional applications of metallic glasses.

PMID- 22639728
TI  - Template-cut: a pattern-based segmentation paradigm.
AB  - We present a scale-invariant, template-based segmentation paradigm that sets up a
      graph and performs a graph cut to separate an object from the background.
      Typically graph-based schemes distribute the nodes of the graph uniformly and
      equidistantly on the image, and use a regularizer to bias the cut towards a
      particular shape. The strategy of uniform and equidistant nodes does not allow
      the cut to prefer more complex structures, especially when areas of the object
      are indistinguishable from the background. We propose a solution by introducing
      the concept of a "template shape" of the target object in which the nodes are
      sampled non-uniformly and non-equidistantly on the image. We evaluate it on 2D
      images where the object's textures and backgrounds are similar, and large areas
      of the object have the same gray level appearance as the background. We also
      evaluate it in 3D on 60 brain tumor datasets for neurosurgical planning purposes.

PMID- 22639729
TI  - The phonon theory of liquid thermodynamics.
AB  - Heat capacity of matter is considered to be its most important property because
      it holds information about system's degrees of freedom as well as the regime in
      which the system operates, classical or quantum. Heat capacity is well understood
      in gases and solids but not in the third main state of matter, liquids, and is
      not discussed in physics textbooks as a result. The perceived difficulty is that
      interactions in a liquid are both strong and system-specific, implying that the
      energy strongly depends on the liquid type and that, therefore, liquid energy can
      not be calculated in general form. Here, we develop a phonon theory of liquids
      where this problem is avoided. The theory covers both classical and quantum
      regimes. We demonstrate good agreement of calculated and experimental heat
      capacity of 21 liquids, including noble, metallic, molecular and hydrogen-bonded
      network liquids in a wide range of temperature and pressure.

PMID- 22639730
TI  - Dynamic mechanism for the transcription apparatus orchestrating reliable
      responses to activators.
AB  - The transcription apparatus (TA) is a huge molecular machine. It detects the time
      varying concentrations of transcriptional activators and initiates mRNA
      transcripts at appropriate rates. Based on the general structural organizations
      of the TA, we propose how the TA dynamically orchestrates transcriptional
      responses. The activators rapidly cycle in and out of a clamp-like space
      temporarily formed between the enhancer and the Mediator, with the concentration
      of activators encoded as their temporal occupancy rate (R(TOR)) within the space.
      The entry of activators into this space induces allostery in the Mediator,
      resulting in a facilitated circumstance for transcriptional reinitiation. The
      reinitiation rate is much larger than the cycling rate of activators, thereby
      R(TOR) guiding the amount of transcripts. Based on this mechanism, stochastic
      simulations can qualitatively reproduce and interpret multiple features of gene
      expression, e.g., transcriptional bursting is not mere noise as traditionally
      believed, but rather the basis of reliable transcriptional responses.

PMID- 22639731
TI  - Characterizing global evolutions of complex systems via intermediate network
      representations.
AB  - Recent developments in measurement techniques have enabled us to observe the time
      series of many components simultaneously. Thus, it is important to understand not
      only the dynamics of individual time series but also their interactions. Although
      there are many methods for analysing the interaction between two or more time
      series, there are very few methods that describe global changes of the
      interactions over time. Here, we propose an approach to visualise time evolution
      for the global changes of the interactions in complex systems. This approach
      consists of two steps. In the first step, we construct a meta-time series of
      networks. In the second step, we analyse and visualise this meta-time series by
      using distance and recurrence plots. Our two-step approach involving intermediate
      network representations elucidates the half-a-day periodicity of foreign exchange
      markets and a singular functional network in the brain related to perceptual
      alternations.

PMID- 22639732
TI  - AROUSAL FROM SLICES TO HUMANS: Translational studies on sleep-wake control.
AB  - Most psychiatric and neurological disorders exhibit sleep disorders, and in some
      cases presage the disease. Study of the control of sleep and waking has the
      potential for making a major impact on a number of disorders, making
      translational neuroscience research on this area critical. One element of the
      reticular activating system (RAS) is the pedunculopontine nucleus (PPN), which is
      the cholinergic arm of the RAS, and projects to the thalamus to trigger
      thalamocortical rhythms and to the brainstem to modulate muscle tone and
      locomotion. We developed a research program using brainstem slices containing the
      PPN to tell us about the cellular and molecular organization of this region. In
      addition, we developed the P13 midlatency auditory evoked potential, which is
      generated by PPN outputs, preparation in freely moving rats. This allows the
      study of PPN cellular and molecular mechanisms at the level of the whole animal.
      We also study the P50 midlatency auditory evoked potential, which is the human
      equivalent of the rodent P13 potential, allowing us to study processes detected
      in vitro, confirmed in the whole animal, and tested in humans. This translational
      research program led to the discovery of a novel mechanism of sleep-wake control,
      pointing the way to a number of new clinical applications in the development of
      novel stimulants and anesthetics.

PMID- 22639733
TI  - Associations between Physical Activity and Submaximal Cardiorespiratory and
      Pulmonary Responses in Men.
AB  - BACKGROUND: Habitual physical activity (PA) is associated with higher
      cardiorespiratory fitness values, but additional information is needed on the
      contributions of specific types and amounts of PA. Therefore the main aim of this
      study was to analyze the heart and lung function of a large cohort of men and
      compare these outcomes with various modes and volumes of PA.  METHODS: We used
      data from 30,594 men from the Aerobics Center Longitudinal Study who were
      categorized into sedentary, swimmer, walker, and runner groups using self-report
      PA data collected during 1970-2005. Additional PA categories using MET
      minutes/week were used to group men into 5 distinct levels of activity (0 MET
      min, 1-499 MET-min, 500-999 MET-min, 1000-1499 MET-min, and >= 1500 MET-min).
      Each participant also completed a maximal treadmill exercise test to quantify
      their fitness level. Cross-sectional analyses included general linear modeling
      and multiple comparisons adjusted for age, smoking status, and histories of
      myocardial infarction, stroke, diabetes, and hypertension.  RESULTS: A dose
      response linear effect was found for heart function variables across PA MET-min
      categories. Stronger associations for resting heart rate (HR), heart rate
      recovery (HRR), exercise HR, and exercise blood pressure were found with the
      runner and swimming groups when compared to the walkers and sedentary groups.
      Walkers had significantly better heart function than the sedentary group but only
      about half the effect seen in the swimmers and runners. Lung function findings
      showed greater absolute values in FVC and FEV1 across PA categories, but found no
      difference in lung function ratios (e.g FEV1/FVC%).  CONCLUSIONS: We found
      beneficial linear associations with resting HR, exercise HR, HRR, fitness values,
      FVC, and FEV1 over increasing MET-min categories. This implies that habitual PA,
      such as walking, but especially swimming and running, when performed with
      adequate volume, are viable ways to gain benefits for heart health.

PMID- 22639734
TI  - Guanidine-Containing Methacrylamide (Co)polymers via aRAFT: Toward a Cell
      Penetrating Peptide Mimic().
AB  - We report the synthesis and controlled radical homo- and block copolymerization
      of 3-guanidinopropyl methacrylamide (GPMA) utilizing aqueous reversible addition
      fragmentation chain transfer (aRAFT) polymerization. The resulting homopolymer
      and block copolymer with N-(2-hydroxypropyl) methacrylamide (HPMA) were prepared
      to mimic the behavior of cell penetrating peptides (CPPs) and poly(arginine) (> 6
      units) which have been shown to cross cell membranes. The homopolymerization
      mediated by 4-cyano-4-(ethylsulfanylthiocarbonylsulfanyl)pentanoic acid (CEP) in
      aqueous buffer exhibited pseudo-first-order kinetics and linear growth of
      molecular weight with conversion. Retention of the "living" thiocarbonylthio
      omega-end-group was demonstrated through successful chain extension of the GPMA
      macroCTA yielding GPMA(37)-b-GPMA(61) (M(w)/M(n) =1.05). Block copolymers of GPMA
      with the non-immunogenic, biocompatible HPMA were synthesized yielding HPMA(271)
      b-GPMA(13) (M(w)/M(n) = 1.15). Notably, intracellular uptake was confirmed by
      fluorescence microscopy, confocal laser scanning microscopy, and flow cytometry
      experiments after 2.5 h incubation with KB cells at 4  degrees C and at 37 
      degrees C utilizing FITC-labeled, GPMA-containing copolymers. The observed
      facility of cellular uptake and the structural control afforded by aRAFT
      polymerization suggest significant potential for these synthetic (co)polymers as
      drug delivery vehicles in targeted therapies.

PMID- 22639735
TI  - Ultrasensitive synthetic protein regulatory networks using mixed decoys.
AB  - Cellular protein interaction networks exhibit sigmoidal input-output
      relationships with thresholds and steep responses (i.e., ultrasensitivity).
      Although cooperativity can be a source of ultrasensitivity, we examined whether
      the presence of "decoy" binding sites that are not coupled to activation could
      also lead to this effect. To systematically vary key parameters of the system, we
      designed a synthetic regulatory system consisting of an autoinhibited PDZ domain
      coupled to an activating SH3 domain binding site. In the absence of a decoy
      binding site, this system is non-ultrasensitive, as predicted by modeling of this
      system. Addition of a high-affinity decoy site adds a threshold, but the response
      is not ultrasensitive. We found that sigmoidal activation profiles can be
      generated utilizing multiple decoys with mixtures of high and low affinities,
      where high affinity decoys act to set the threshold and low affinity decoys
      ensure a sigmoidal response. Placing the synthetic decoy system in a mitotic
      spindle orientation cell culture system thresholds this physiological activity.
      Thus, simple combinations of non-activating binding sites can lead to complex
      regulatory responses in protein interaction networks.

PMID- 22639737
TI  - Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7
      Human Breast Cancer.
AB  - OBJECTIVES: In recent years, a number of structurally diverse Histone deacetylase
      (HDAC) inhibitors have been identified and these HDAC inhibitors induce growth
      arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo.
      This study aimed at investigating the anti-tumor activity of newly synthesized
      HDAC inhibitor, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide (IN-2001)
      using human breast cancer cells. METHODS: We have synthesized a new HDAC
      inhibitor, IN-2001, and cell proliferation inhibition assay with this chemical in
      estrogen receptor-positive human breast cancer MCF-7 cells. Cell cycle analysis
      on MCF-7 cells treated with IN-2001 was carried out by flow cytometry and gene
      expression was measured by RT-PCR. RESULTS: In MCF-7 cells IN-2001 showed
      remarkable anti-proliferative effects in a dose- and time-dependent manner. In
      MCF-7 cells, IN-2001 showed a more potent growth inhibitory effect than that of
      suberoylanilide hydroxamic acid. These growth inhibitory effects were related to
      the cell cycle arrest and induction of apoptosis. IN-2001 showed accumulation of
      cells at G(2)/M phase and of the sub-G(1) population in a time-dependent manner,
      representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated
      with HDAC inhibitor-mediated induction of CDK inhibitor expression. In MCF-7
      cells, IN-2001 significantly increased p21(WAF1) expression. CONCLUSIONS: In
      summary, cyclin-dependent kinase (CDK) induced growth inhibition, possibly
      through modulation of cell cycle and apoptosis regulatory proteins, such as CDK
      inhibitors, and cyclins. Taken together, these results provide an insight into
      the utility of HDAC inhibitors as a novel chemotherapeutic regime for hormone
      sensitive and insensitive breast cancer.

PMID- 22639738
TI  - Acetaminophen induced cytotoxicity and altered gene expression in cultured
      cardiomyocytes of h(9)c(2) cells.
AB  - OBJECTIVES: Hepatotoxicity of acetaminophen has been widely studied. However, the
      adverse effects on the heart have not been sufficiently evaluated. This study was
      performed to investigate cytotoxicity and alterations of gene expression in
      cultured cardiomyocytes (H(9)C(2) cells) after exposure to acetaminophen.
      METHODS: H(9)C(2) cells were incubated in a 10 mM concentration of acetaminophen
      for the designated times (6, 12, and 24 hours), and cytotoxicity was determined
      by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.
      Alteration of gene expression was observed by microarray analysis, and RT-PCR was
      performed for the three representative oxidative stress-related genes at 24 hours
      after treatment. RESULTS: It revealed that acetaminophen was toxic to
      cardiomyocytes, and numerous critical genes were affected. Induced genes included
      those associated with oxidative stress, DNA damage, and apoptosis. Repressed
      genes included those associated with cell proliferation, myocardial contraction,
      and cell shape control. CONCLUSIONS: These findings provide the evidences of
      acetaminophen-induced cytotoxicity and changes in gene expression in cultured
      cardiomyocytes of H(9)C(2) cells.

PMID- 22639739
TI  - The characteristics of the appearance and health risks of volatile organic
      compounds in industrial (pohang, ulsan) and non-industrial (gyeongju) areas.
AB  - OBJECTIVES: The aim of this study was to identify the health and environmental
      risk factors of air contaminants that influence environmental and respiratory
      diseases in Gyeongju, Pohang and Ulsan in South Korea, with a focus on volatile
      organic compounds (VOCs). METHODS: Samples were collected by instantaneous
      negative pressure by opening the injection valve in the canister at a fixed
      height of 1 to 1.5 m. The sample that was condensed in -150C was heated to 180C
      in sample pre-concentration trap using a 6-port switching valve and it was
      injected to a gas chromatography column. The injection quantity of samples was
      precisely controlled using an electronic flow controller equipped in the gas
      chromatography-mass spectrometer. RESULTS: The quantity of the VOC emissions in
      the industrial area was 1.5 to 2 times higher than that in the non-industrial
      area. With regards to the aromatic hydrocarbons, toluene was detected at the
      highest level of 22.01 ppb in Ulsan, and chloroform was the halogenated
      hydrocarbons with the highest level of 10.19 ppb in Pohang. The emission of
      toluene was shown to be very important, as it accounted for more than 30% of the
      total aromatic hydrocarbon concentration. CONCLUSIONS: It was considered that
      benzene in terms of the cancer-causing grade standard, toluene in terms of the
      emission quantity, and chloroform and styrene in terms of their grades and
      emission quantities should be selected for priority measurement substances.

PMID- 22639740
TI  - The Relationship between Cross Sectional Area and Strength of Back Muscles in
      Patients with Chronic Low Back Pain.
AB  - OBJECTIVE: To evaluate the relationship between the cross sectional area (CSA)
      and isokinetic strength of the back muscles in patients with chronic low back
      pain. METHOD: Data of twenty-eight middle-aged patients with chronic back pain
      were analyzed retrospectively. CSAs of both paraspinal muscles and the disc at
      the L4-L5 level were measured in MRI axial images and the relative CSAs (rCSA:
      CSA ratio of muscle and disc) were calculated. The degree of paraspinal muscle
      atrophy was rated qualitatively. Isokinetic strengths (peak torque, peak torque
      per body weight) of back flexor and extensor were measured with the isokinetic
      testing machine. Multiple regression analysis with backward elimination was used
      to evaluate relations between isokinetic strength and various factors, such as
      CSA or rCSA and clinical characteristics in all patients. The same analysis was
      repeated in the female patients. RESULTS: In analysis with CSA and clinical
      characteristics, body mass index (BMI) and CSA were significant influencing
      factors in the peak torque of the back flexor muscles. CSA was a significant
      influencing factor in the peak torque of total back muscles. In analysis with
      rCSA and clinical characteristics, BMI was significant in influencing the peak
      torque of the back flexors. In female patients, rCSA was a significant
      influencing factor in the peak torque per body weight of the back flexors, and
      age and BMI were influencing factors in the peak torque of back flexors and total
      back muscles. CONCLUSION: In middle-aged patients with chronic low back pain, CSA
      and rCSA were influencing factors in the strength of total back muscles and back
      flexors. Also, gender and BMI were influencing factors.

PMID- 22639741
TI  - Optimal stimulation site for deep peroneal motor nerve conduction study around
      the ankle: cadaveric study.
AB  - OBJECTIVE: To identify the optimal distal stimulation point for conventional deep
      peroneal motor nerve (DPN) conduction studies by a cadaveric dissection study.
      METHOD: DPN was examined in 30 ankles from 20 cadavers. The distance from the DPN
      to the tibialis anterior (TA) tendon was estimated at a point 8 cm proximal to
      the extensor digitorum brevis (EDB) muscle. Relationships between the DPN and
      tendons including TA, extensor hallucis longus (EHL), and extensor digitorum
      longus (EDL) tendons were established. RESULTS: The median distance from the DPN
      to the TA tendon in all 30 cadaver ankles was 10 mm (range, 1-21 mm) at a point 8
      cm proximal to the EDB muscle. The DPN was situated between EHL and EDL tendons
      in 18 cases (60%), between TA and EHL tendons in nine cases (30%), and lateral to
      the EDL tendon in three cases (10%). CONCLUSION: The optimal distal stimulation
      point for the DPN conduction study was approximately 1 cm lateral to the TA
      tendon at the level of 8 cm proximal to the active electrode. The distal
      stimulation site for the DPN should be reconsidered in cases with a weaker distal
      response but without an accessory peroneal nerve.

PMID- 22639742
TI  - Surface mapping of motor points in biceps brachii muscle.
AB  - OBJECTIVE: To localize the site of motor points within human biceps brachii
      muscles through surface mapping using electrophysiological method. METHOD: We
      recorded the compound muscle action potentials of each lattice of the biceps
      brachii in 40 healthy subjects. Standardized reference lines were made as the
      following: 1) a horizontal reference line (elbow crease) and 2) a vertical
      reference line connecting coracoid process and mid-point of the horizontal
      reference line. The Compound muscle action potentials were mapped in reference to
      the standardized reference lines. The locations of motor points were mapped to
      the skin surface, in the ratio to the length of the vertical and the half of the
      horizontal reference lines. RESULTS: The motor point of the short head of biceps
      was located at 69.0+/-4.9% distal and 19.1+/-9.5% medial to the mid-point of
      horizontal reference line. The location of the motor point of the long head of
      the biceps was 67.3+/-4.3% distal and 21.4+/-8.7% lateral. The motor point of the
      short head of the biceps was located more medially and distally in the male
      subjects compared to that in the female (p<0.05). CONCLUSION: This study showed
      electrophysiological motor points of the biceps brachii muscles through surface
      mapping. This data might improve the clinical efficacy and the feasibility of
      motor point targeting, when injecting botulinum neurotoxin in biceps brachii.

PMID- 22639743
TI  - The effect of human placental extract on rheumatoid arthritis in an animal model.
AB  - OBJECTIVE: To assess the efficacy of human placental extract (HPE) in an animal
      model of rheumatoid arthritis (RA). METHOD: We used (i) KRN C57BL/6 TCR
      transgenic x NOD mice (KBx/N) serum transfer arthritis and (ii) collagen-induced
      arthritis (CIA) mice to evaluate the effi cacy of HPE (1 ul or 100 ul, intra
      peritoneal, three times per week) on RA. Incidence, severity of arthritis, and
      hind-paw thickness were quantifi ed. Joint destruction was analyzed using modifi
      ed mammographic imaging. Histopathological analysis for inflammation, cartilage,
      and osteoclasts was performed using Hematoxylin-eosin (H-E), safranin-O, and
      tartrate-resistant acidic phosphatase (TRAP). ELISAs were used for detection of
      various cytokines in serum and joint tissue. RESULTS: There were no significant
      differences in incidence of arthritis, clinical scores of arthritis, and hind-paw
      thickness between HPE-treated and vehicle-treated groups for up to 2 weeks in the
      KBx/N serum transfer arthritis model. Histopathological analysis also showed no
      differences 2 weeks after treatment. Levels of TNF-alpha, IL-1beta, IL-6, IL-10,
      and RANKL in serum and joint tissues were similar in all groups. Furthermore,
      there were no differences in clinical, radiological, and histological parameters
      between HPE-treated and vehicle-treated group for 3 weeks in the CIA model.
      CONCLUSION: Systemic treatment with HPE has no beneficial effects on arthritis in
      animal models of RA. Therefore, indiscreet use of HPE in RA should be forbidden.

PMID- 22639744
TI  - The effect of leflunomide on cold and vibratory sensation in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the prevalence and risk factors of peripheral neuropathy
      in patients with rheumatoid arthritis (RA) treated with leflunomide (LEF) by
      quantitative sensory testing (QST). METHOD: A total of 94 patients were
      enrolledin this study, out of which 47 patients received LEF. The other 47
      patients received alternative disease-modifying antirheumatic drugs and served as
      the control group. The demographic characteristics, laboratory findings,
      concomitant diseases, and medication history were evaluated at the time of QST.
      The cooling (CDT) and vibratory detection threshold (VDT) as the representative
      components of QST were measured. RESULTS: Age, gender, RA duration, ESR, and CRP
      did not show any significant differences between the two groups. VDT did not
      demonstrate any significant difference in both groups. However, CDT in LEF group
      was significantly higher than that of the control group (8.6+/-2.7 in LEF vs.
      5.6+/-3.8 in control). The proportion of RA patients in the LEF group showing
      abnormally high CDT was over 2 times greater than that of the control group, but
      these findings were not statistically significant. Age, RA duration (or LEF
      medication in LEF group), ESR, and CRP did not show significant correlation with
      CDT in both groups. VDT significantly correlated with age in both groups.
      CONCLUSION: LEF treatment in patients with RA may lead to abnormal CDT in QST.
      CDT value was not affected by age, RA duration, disease activity, or LEF
      duration. It remains to be determined whether QST may be a valuable non-invasive
      instrument to evaluate the early sensory changes in patients with RA taking LEF.

PMID- 22639745
TI  - Radiofrequency sacral rhizotomy for the management of intolerable neurogenic
      bladder in spinal cord injured patients.
AB  - OBJECTIVE: To investigate the effect of radiofrequency (RF) sacral rhizotomy of
      the intolerable neurogenic bladder in spinal cord injured patients. METHOD:
      Percutaneous RF sacral rhizotomy was performed on 12 spinal cord injured patients
      who had neurogenic bladder manifested with urinary incontinence resisted to an
      oral and intravesical anticholinergic instillation treatment. Various
      combinations of S2, S3, and S4 RF rhizotomies were performed. The urodynamic
      study (UDS) was performed 1 week before RF rhizotomy. The voiding
      cystourethrogram (VCUG) and voiding diaries were compared 1 week before and 4
      weeks after therapy. Total volume of daily urinary incontinence (ml/day) and
      clean intermittent catheterization (ml/time) volume of each time were also
      monitored. RESULTS: After RF sacral rhizotomy, bladder capacity increased in 9
      patients and the amount of daily urinary incontinence decreased in 11 patients.
      The mean maximal bladder capacity increased from 292.5 to 383.3 ml (p<0.05) and
      mean daily incontinent volume decreased from 255 to 65 ml (p<0.05). Bladder
      trabeculation and vesicoureteral reflux findings did not change 4 weeks after
      therapy. CONCLUSION: This study revealed that RF sacral rhizotomy was an
      effective method for neurogenic bladder with uncontrolled incontinence using
      conventional therapy among spinal cord injured patients.

PMID- 22639746
TI  - The Effects of Bolus Consistency in Pharyngeal Transit Duration during Normal
      Swallowing.
AB  - OBJECTIVE: To examine the effects of age, gender and bolus consistency in normal
      populations using the temporal measurement of Pharyngeal Transit Duration (PTD),
      which reflects the duration of bolus flow from the ramus of the mandible to the
      upper esophageal sphincter. METHOD: 40 normal and healthy subjects had
      Videofluoroscopic Swallowing Examinations (VFSEs) of 5 ml thin and nectar thick
      liquids, and puree consistencies. A slow motion and frame by frame analysis was
      performed. Three-way analysis of variance (ANOVA) was performed to examine the
      main effect and interactions, and paired t-tests for the three consistency
      comparisons. RESULTS: Older subjects had a significantly longer PTD than younger
      subjects (p<0.01). In addition, men had significantly shorter PTDs than women
      (p<0.01). Puree showed a significantly longer PTD than the other two
      consistencies, regardless of age and gender (p<0.05). CONCLUSION: PTD is an
      indicative of motor weakness in pharyngeal swallowing secondary to aging. In
      addition, the results supported the assumption that there is a functional
      difference in pharyngeal swallowing between men and women. It is expected that
      the results of this study will be used for further investigation of patients with
      dysphagia.

PMID- 22639747
TI  - Effects of night sleep on motor learning using transcranial magnetic stimulation.
AB  - OBJECTIVE: To investigate the effects of night sleep on motor cortical
      excitability with TMS (transcranial magnetic stimulation) and finger tapping
      performance. METHOD: Eight volunteers were enrolled to investigate the effects of
      day wake or night sleep on motor learning and finger performance. Each subject
      underwent a finger tapping task over a 12 hour period, which was employed to
      evaluate the motor cortical excitability affected by motor learning. Starting at
      9:00 am for the day wake cycle and restarting at 9:00 pm for the night sleep
      cycle. The finger tapping task was the index finger of the non-dominant hand with
      the Hangul word personal computer (PC) training program. The data was assessed by
      comparing the changes observed with the cortical excitability and finger tapping
      performance tests between the day wake and night sleep after equivalent amounts
      of training. RESULTS: The results showed that in paired-pulse techniques, there
      was a significant decrease of intracortical inhibition (ICI) in the morning
      following the night sleep cycle (p<0.05), but no significant change was seen in
      the ICI in the evening for the day wake cycle. In addition a significant decrease
      of the ICI was observed in comparison to the morning following the night sleep
      cycle and the evening following the day wake cycle (p<0.05). The 140% recruitment
      curve (RC) and accuracy of the finger tapping performance demonstrated a
      significant improvement for both cycles (p<0.05). CONCLUSION: Through this study,
      we observed that the Hangul typing practice requires both explicit and implicit
      skill learning. And also the off-line learning during a night of sleep may be
      affected by an inhibitory neurotransmitter related synaptic plasticity and by the
      time dependent learning with recruitments of remote or less excitable motor
      neurons in the primary motor cortex.

PMID- 22639748
TI  - Inter-rater Reliability of the K-GMFM-88 and the GMPM for Children with Cerebral
      Palsy.
AB  - OBJECTIVE: To examine inter-rater reliability of the Korean version Gross Motor
      Function Measure (K-GMFM-88) and the Gross Motor Performance Measure (GMPM) based
      on the video clips. METHOD: We considered a sample of 39 children (28 boys and 11
      girls; the mean age=3.50+/-1.23 years) with cerebral palsy (CP). Two pediatric
      physical therapists assessed the children based on video recordings. RESULTS: For
      the K-GMFM-88, the intraclass correlation coefficient (ICC(3, 1)) ranged from
      .978 to .995, and Spearman's correlation coefficient ranged from .916 to .997.
      For the GMPM, ICC(3, 1) ranged from .863 to .929, and Spearman's correlation
      coefficient ranged from .812 to .885. With the gross motor function
      classification system classified according to the functional level (GMFCS I-II
      vs. III-V), the ICCs were .982 and .994 for the K-GMFM-88 total score and .815
      and .913 for the GMPM total score. There were good or high correlations between
      the subscales of the two measures (r=.762-.884). CONCLUSION: The K-GMFM-88 and
      GMPM are reliable tools for assessing the motor function of children with CP.
      These two methods are highly correlated, which adds more reliability on them.
      Thus, it is advisable to use K-GMFM-88 and GMPM for children with CP to assess
      gross motor function.

PMID- 22639749
TI  - Quality of life, upper extremity function and the effect of lymphedema treatment
      in breast cancer related lymphedema patients.
AB  - OBJECTIVE: To evaluate quality of life (QOL), upper extremity function and the
      effect of lymphedema treatment in patients with breast cancer related lymphedema.
      METHOD: The basic data comprised medical records (detailing age, sex, dominant
      side, location of tumor, cancer stage, operation record, cancer treatment and
      limb circumferences) and questionnaires (lymphedema duration, satisfaction, self
      massage). Further to this, we measured upper extremity function and QOL,
      administered the DASH (Disabilities of Arm Shoulder and Hand outcome measure) and
      used the EORTC (European Organization for Research and Treatment of Cancer)-QLQ
      C30 and the EORTC-QLQ-Br23. Results of these were calculated as main outcome
      variables. RESULTS: The questionnaire responses and arm circumferences of 59
      patients with breast cancer related lymphedema were analyzed. In the DASH
      questionnaire, it was found that the older the lymphedema patient was, the lower
      their upper extremity function. On the EORTC-QLQ, patients with metastasis had
      significantly lower scores in physical functioning and role functioning. In terms
      of upper extremity circumference, there was a significant upper extremity size
      reduction after lymphedema treatment. CONCLUSION: There were several
      dissociations between some subscales of quality of life questionnaires and those
      of upper extremity functions. Upper extremity function was correlated with the
      age of breast cancer patients and QOL was influenced by M-stage. Lymphedema
      treatment was found to be effective in reducing edema in patients with breast
      cancer related lymphedema.

PMID- 22639750
TI  - The Relation between Postvoid Residual and Occurrence of Urinary Tract Infection
      after Stroke in Rehabilitation Unit.
AB  - OBJECTIVE: To determine the relation between postvoid residual (PVR) and the
      occurrence of urinary tract infection (UTI) in stroke patients. METHOD: One
      hundred and eighty-eight stroke patients who were admitted to an inpatient
      rehabilitation unit and who did not have UTI on admission (105 males, 83 females,
      mean age 67.1 years) were included in this study. The PVR was measured 3 times
      within 72 hours after admission. Mean PVR, demographic variables, K-MMSE (Korean
      Mini-Mental State Examination), initial K-MBI (Korean Modified Barthel Index),
      Foley catheter indwelling time and stroke type were defined and the relation to
      the occurrence of UTI was analyzed. RESULTS: UTI occurred in 74 patients (39.4%)
      during admission to the rehabilitation unit. There were significant differences
      between the UTI and non-UTI groups in K-MMSE, K-MBI, Foley catheter indwelling
      time (p<0.01). However, age, gender, stroke location and type were not
      associated. The occurrence of UTI was 4.87 times higher in the patients with a
      mean PVR over 100 ml than in those with a mean PVR <100 ml. The mean PVR was
      106.5 ml in the UTI group, while it was 62.7 ml in the non-UTI group (p<0.01).
      PVR was not associated with age. CONCLUSION: The UTI rate is higher when the mean
      PVR is over 100 ml irrespective of gender and age. Close monitoring of PVR and
      appropriate intervention is needed to reduce the occurrence of UTI in stroke
      patients.

PMID- 22639751
TI  - Impact of Exercise-based Cardiac Rehabilitation on In-stent Restenosis with
      Different Generations of Drug Eluting Stent.
AB  - OBJECTIVE: To compare the rate of restenosis between a cardiac rehabilitation
      (CR) group and a control group within three different generations of drug eluting
      stents (DES). METHOD: Patients who received DES due to an acute coronary syndrome
      were included. They were divided into a CR group and a control group. The CR
      group received six to eight weeks of early cardiac rehabilitation program in a
      hospital setting, and sustained a self-exercise program for six months in a
      community. The control group was instructed to exercise by themselves after
      leaving the hospital. Nine months after the first onset of disease, we
      implemented a coronary angiography and compared the two groups. In addition, we
      divided the patients into three subgroups according to the generation of DES, and
      compared the rate of restenosis between the CR group and control group within
      these three subgroups. RESULTS: At 9 months, in-stent restenosis, measured as an
      in-segment late luminal loss (LLL) of the stented coronary area, was smaller in
      the CR group (n=52) 0.16+/-0.42 mm compared to the control group (n=51) 0.39+/
      0.78 mm (p<0.05). A reduction of LLL in the CR group compared to the control
      group was consistent among the three different generations of DES. CONCLUSION:
      The CR program is strongly associated with a significant reduction in LLL in the
      stented coronary segments, regardless of the generation of DES.

PMID- 22639752
TI  - Safety of Monitoring Exercise for Early Hospital-based Cardiac Rehabilitation.
AB  - OBJECTIVE: To survey the cardiovascular complications induced by cardiac
      monitoring exercise during 10 years of our cardiac rehabilitation (CR) clinic and
      report on the safety of monitoring exercise training for early hospital-based CR.
      METHOD: All cardiac patients who participated in our exercise program from
      January 2000 through December 2009 were recruited as study subjects. We
      stratified the exercise risks of cardiac events and conducted the monitoring
      exercise with individualized prescriptions. We measured all cardiac
      complications, including death, symptoms, abnormal hemodynamic responses, and
      electrocardiogram (ECG) abnormality during exercise training, for 10 years. A
      total of 975 patients (68% male; mean age, 58.9+/-10.6) were included in this
      study. Initial indications for CR were recent percutaneous transluminal coronary
      angioplasty (PTCA) (75%), post-cardiac surgery (coronary bypass graft, 13.2%),
      valvular surgery and other cardiac surgery (4.2%), and others (7.6%). RESULTS:
      The study population underwent 13,934 patient-hours of monitoring exercise. No
      death, cardiac arrest or acute myocardial infarction (AMI) occurred during
      exercise (0/13,934 exercise-hours). Fifty-nine patients experienced 70
      cardiovascular events during the 13,934 exercise-hours (1/199 exercise-hours);
      there were 17 cases of angina only (1/820 exercise-hours), 31 cases of ECG
      abnormalities only (1/449 exercise-hours), 12 cases of angina with ECG
      abnormalities (1/1,161 exercise-hours), and 10 cases of abnormal hemodynamic
      responses (1/1,393 exercise-hours). CONCLUSION: Early hospital-based CR is safe
      enough that no death, cardiac arrest or AMI occurred during the 13,934 patient
      hours of monitoring exercise. However, risk stratification for exercise-induced
      cardiovascular events, proper exercise prescriptions, and intensive ECG
      monitoring are required prior to initiation of the monitoring exercise.

PMID- 22639753
TI  - Augmentative and Alternative Communication Training Using Eye Blink Switch for
      Locked-in Syndrome Patient.
AB  - Locked-in Syndrome is a severe pontine stroke causing quadriplegia, lower cranial
      nerve paralysis, and mutism with preservation of only vertical gaze and upper
      eyelid movement in a conscious patient. We present a case of a Locked-in Syndrome
      patient who received communication training with augmentative and alternative
      communication equipment by using eye blinks. After 3 weeks of training, the
      patient was able to make an attempt to interact with other people, and associate
      a new word by Korean alphabet selection. Augmentative and alternative
      communication equipment which uses eye blinks might be considered to be
      beneficial in improving the communication skills of locked-in syndrome patients.

PMID- 22639754
TI  - Femoral neuropathy and meralgia paresthetica secondary to an iliacus hematoma.
AB  - Compressive femoral and lateral femoral cutaneous neuropathies from an iliacus
      hematoma are unusual presentation. We report a case of a 16-year-old boy who
      developed right femoral and lateral femoral cutaneous neuropathies as a
      complication of traumatic ipsilateral iliacus hematoma formation. The patient
      complained of numbness in the right thigh and calf as well as right leg weakness,
      and pain in the right inguinal area. Nerve conduction study and needle
      electromyography identified the neuropathies. After the electrodiagnostic
      studies, the pelvic bone MRI revealed a large, 9*5*4.5 cm right iliacus hematoma.
      As a result, diagnosis of a right iliacus hematoma compressing the femoral and
      lateral femoral cutaneous nerves was made, and the patient underwent an operation
      to remove the hematoma. Symptoms and neurological signs showed notable
      improvement after surgical decompression. Subsequent follow-up electrodiagnostic
      studies after 11 weeks demonstrated regeneration evidence.

PMID- 22639756
TI  - Back pain secondary to Brucella spondylitis in the lumbar region.
AB  - Brucellosis is a systemic, infectious disease caused by the bacterial genus
      Brucella and a common zoonosis that still remains a major health problem in
      certain parts of the world such as the Mediterranean region, the Middle East, and
      Latin America. It may involve multiple organs and tissues. Osteoarticular
      involvement is the most frequent complication of brucellosis, in which the
      diagnosis of brucellar spondylitis is often difficult since the clinical
      presentation may be obscured by many other conditions. There are only a few
      reports on brucellar spondylitis in Korea. Here, we report a case of spondylitis
      due to brucella in an elderly male.

PMID- 22639755
TI  - Occurrence of Intestinal Pseudo-obstruction in a Brainstem Hemorrhage Patient.
AB  - Intestinal pseudo-obstruction is a massive colonic dilation with signs and
      symptoms of colonic obstruction, but without a mechanical cause. A 49-year-old
      female patient complained of nausea, vomiting, and abdominal distension 1 month
      after a massive brainstem hemorrhage. No improvement was seen with conservative
      treatments. An extended-length rectal tube was inserted to perform glycerin
      enema. In addition, bethanechol (35 mg per day) was administered to stimulate
      colonic motility. The patient's condition gradually improved over a 2-month
      period without any surgical intervention. Extended length rectal tube enema and
      bethanechol can be used to improve intestinal pseudo-obstruction in stroke
      patients.

PMID- 22639757
TI  - Arteriovenous malformation incidentally found by ultrasonography in a thigh
      hematoma after contusion.
AB  - Vascular malformations in extremities are difficult to detect in cases of minor
      trauma. The authors report a case of an arteriovenous malformation (AVM)
      incidentally found by ultrasonography in a contusion. After a slip down, a 52
      year-old man who had undergone total arthroplasty in both hips 10 years earlier
      complained of an ovoid right hip swelling that had gradually increased in size.
      Suspecting a simple cyst or hematoma, the swelling was examined by
      ultrasonography, which revealed a subcutaneous hematoma with arterial flow
      connected to muscle. Arteriography revealed an AVM around the right hip joint.
      Due to the presence of multiple arteriovenous shunts, a conservative treatment
      course was adopted and after 3 weeks of treatment the swelling almost completely
      resolved. It appears that the small AVM may have existed congenitally before hip
      surgery and the contusion over the AVM had led to hematoma rather than an
      arteriovenous fistula. The authors emphasize the usefulness of ultrasonography
      for the diagnosis of posttraumatic swelling.

PMID- 22639758
TI  - Ulnar neuropathy at the wrist in a patient with carpal tunnel syndrome after open
      carpal tunnel release.
AB  - Ulnar neuropathy at the wrist is rarely reported as complications of carpal
      tunnel release. Since it can sometimes be confused with recurrent median
      neuropathy at the wrist or ulnar neuropathy at the elbow, an electrodiagnostic
      study is useful for detecting the lesion in detail. We present a case of a 51
      year-old woman with a two-week history of right ulnar palm and 5(th) digit
      tingling sensation that began 3 months after open carpal tunnel release surgery
      of the right hand. Electrodiagnostic tests such as segmental nerve conduction
      studies of the ulnar nerve at the wrist were useful for localization of the
      lesion, and ultrasonography helped to confirm the presence of the lesion. After
      conservative management, patient symptoms were progressively relieved. Combined
      electrodiagnostic studies and ultrasonography may be helpful for diagnosing and
      detecting ulnar neuropathies of the wrist following carpal tunnel release
      surgery.

PMID- 22639759
TI  - Spinal Cord Infarction Caused by Non-dissected and Unruptured Thoracoabdominal
      Aortic Aneurysm with Intraluminal Thrombus.
AB  - Spinal cord infarction, especially anterior spinal artery syndrome, is a
      relatively rare disease. We report a case of spinal cord infarction caused by
      thoracoabdominal aortic aneurysm with intraluminal thrombus. A 52-year-old man
      presented with sudden onset paraplegia. At first, he was diagnosed with cervical
      myelopathy due to a C6-7 herniated intervertebral disc, and had an operation for
      C6-7 discetomy and anterior interbody fusion. Approximately 1 month after the
      operation, he was transferred to the department of rehabilitation in our
      hospital. Thoracoabdominal aortic aneurysm with intraluminal thrombus was found
      incidentally on an enhanced computed tomography scan, and high signal intensities
      were detected at the anterior horns of gray matter from the T8 to cauda equina
      level on T2-weighted magnetic resonance imaging. There was no evidence of aortic
      rupture, dissection, or complete occlusion of the aorta. We diagnosed his case as
      a spinal cord infarction caused by thoracoabdominal aortic aneurysm with
      intraluminal thrombus.

PMID- 22639760
TI  - The role of social understanding and empathic disposition in young children's
      responsiveness to distress in parents and peers.
AB  - The second year of life marks the beginning of empathic responsiveness to others'
      distress, a hallmark of human interaction. We examined the role of social
      understanding (self-other understanding and emotion understanding) and empathic
      disposition in individual differences in 12- to 24-month olds' responses to
      mothers' and an unfamiliar infant peer's distress (N = 71). Results reveal
      associations between empathic responsiveness to distressed mother and crying
      infant peer, suggesting that individual differences in prosocial motivation may
      exist right from the outset, when the ability to generate an empathic, prosocial
      response first emerges. We further found that above and beyond such dispositional
      characteristics (and age), children with more advanced social understanding were
      more empathically responsive to a peer's distress. However, responses to mothers'
      distress were explained by children's empathic disposition only, and not by their
      social understanding. Thus, as early as the second year of life some children are
      dispositionally more inclined to empathy regardless of who is in distress,
      whether mother or peer. At the same time, emotion understanding and self-other
      understanding appear to be especially important for explaining individual
      differences in young children's empathic responsiveness to a peer's distress.

PMID- 22639761
TI  - Bilateral subcapsular urinomas: an uncommon cause of Page kidney with renal
      failure.

PMID- 22639763
TI  - Ursula H. Poland, AHIP, FMLA, 1922-2009.

PMID- 22639764
TI  - Stephanie L. Normann, 1935-2011.

PMID- 22639765
TI  - Treat challenging patients with understanding, respect.
AB  - When case managers encounter challenging patients and family members, they
      shouldn't take it personally but should recognize that the hospital setting puts
      people under stress. They should try to defuse the situation. Present yourself as
      a supporter and resist the temptation to fight back or just leave the room. Keep
      your emotional health in good shape by educating yourself and getting trained on
      how to cope with difficult situations. Don't set yourself up for failure by
      making assumptions about patients and their viewpoints.

PMID- 22639766
TI  - Don't let patients get you down.

PMID- 22639767
TI  - Avoid making mistakes when dealing with patients.

PMID- 22639768
TI  - Redesign standardizes care coordination.
AB  - By centralizing administrative and clerical tasks usually performed by clinical
      staff, the care coordination department at Sentara Healthcare, with headquarters
      in Norfolk, VA, has freed the bedside staff to concentrate on case management and
      discharge planning. RN care coordinators and master's prepared social workers
      collaborate to manage care on the unit, holding a daily huddle and participating
      in multidisciplinary rounds. Clerical staff set post-discharge appointments with
      primary care providers while the patient is still in the hospital. Staff members
      at a centralized Resource Management Center, created at a new location, are
      responsible for utilization management, including admissions reviews, continuing
      stay reviews, and retrospective reviews and facilitation of discharges for
      patients in all hospitals.

PMID- 22639769
TI  - Providers team up to cut HF readmissions.
AB  - A clinical integration case manager acts as heart failure liaison at Hartford
      Physician Hospital Organization in Hartford, CT. She coordinates care between the
      hospital, Hartford Physicians Association, home health agencies, and skilled
      nursing facilities. The initiative has kept the readmission rate at 11% to 13%.
      The liaison attends heart failure physician rounds and receives most referrals
      during the rounds. She meets the patients in the hospital, then contacts them by
      phone as often as necessary for 30 days or more after discharge. She collaborates
      with staff at the home health agencies and skilled nursing facilities to ensure
      that patients are receiving the care and education they need.

PMID- 22639770
TI  - Multi-faceted program cuts HF readmissions.
AB  - Good Samaritan Hospital Medical Center in West Islip, NY, reduced its heart
      failure readmission rates from 21.1% to 15.3% in just a few months with a
      readmission reduction initiative. A multidisciplinary team researched best
      practices in reducing readmissions and came up with an initiative that includes
      improving the educational process and facilitating smooth care transitions. Team
      members standardized educational materials, by working with other hospitals and
      home care agencies, and they educated the hospital staff and home care agencies
      on the teach-back method. Team members worked with skilled nursing facilities on
      ways to avoid sending heart failure patients back to the hospital. They worked
      with physician offices to ensure that patients obtain a timely followup
      appointment after discharge.

PMID- 22639771
TI  - Rapid intake energizes no-wait ED model.

PMID- 22639772
TI  - [Bishop score and outcome of labor in pregnancy < or = 32 weeks of gestation].
AB  - The purpose of this study was to find correlation between early changes in Bishop
      score and the subsequent method of delivery < or = 32 g.w. MATERIAL AND METHODS:
      A prospective study for five years period (2006 - 2010) included 235 patients who
      met the following criteria: 1) single birth; 2) gestational period < or = 32
      weeks; 3) appropriate for gestational age; 4) livebirths. RESULTS: At admission
      to hospital we found a significant difference in mean Bishop score between those
      delivered vaginally (6.64 p.) and by Cesarean section (2.85 p.) and minor changes
      in Bishop during the time from hospitalization to decision point for CS (3.6 p.).
      In cases with score < or = 5 p. our results showed threefold increased incidence
      of abdominal delivery (53.1% vs. 17.1%). CONCLUSION: Changes in Bishop score at
      admission to hospital in cases of irreversible preterm birth due to spontaneous
      uterine activity or PROM determine the method of delivery < or = 32 weeks.

PMID- 22639773
TI  - [The experience in genetic laboratory Varna in amniocentesis and genetic analysis
      for the period 2006-2010].
AB  - The aim of this report is to present and discuss the results from diagnostic
      amniocenteses, performed in Varna. The test started as a part of a prophylaxis
      program for pregnant women with calculated high risk for chromosomal disorders
      after a screening test. Amniocentesis was performed in total of 283 pregnant
      women. Of all patients who underwent the screening test, amniocentesis was
      performed in 1.55% of women under 36 years of age and 5.0% of women over 36
      years. In the selected group with calculated high risk for chromosomal disorder
      these percentages were 28.5% and 26% respectively. Fetal chromosomal disorder was
      found in 5% (in 7 out of 141) in women under 36 and 3.82% (in 7 out of 83) in
      women over 36 years. Genetic tests (DNA and cytogenetic analysis) of amniocytes
      revealed chromosomal disorders in 16 (5.65%) fetuses (8 with trisomy 21, 3 with
      trisomy 18, 1 with trisomy 13, 1 case with triploidy, 3 cases with structural
      chromosomal rearrangement). Three additional amniocenteses were performed,
      indicated by family history of monogenic disorder (thalassaemia, spinal muscular
      atrophy). The effect of the introduced method for prenatal diagnosis, its
      interaction with the screening tests and their future as genetic prophylaxis
      program are discussed.

PMID- 22639774
TI  - [The experience of the genetic laboratory in Varna on maternal serum screening
      for a six year period].
AB  - The aim of the presentation is to report the results of the Genetic laboratory in
      University hospital "St. Marina" Varna on second (15-19 gw) and first trimester
      (12-14 gw) maternal serum screening for common chromosome disorders, for the
      period 2005-2010. The test was performed on 10741 pregnant women from 8 regions
      of North-Eastern Bulgaria: 9743 women were screened in the second trimester (8251
      at the age < 36 and 1492 at the age > 36) and 998 women - in the first trimester
      (827 at the age < 36 and 171 at the age > 36). The fluorimetric dual method was
      based on biochemical markers; software calculated risk as function of precise
      gestational age, maternal weight and age. The most common strategy was to combine
      the risk as determined from first and second trimester screening test in a
      sequential manner. High risk for a chromosome disorder (a risk above 1:250) was
      found by second trimester screening in 784 (8,04%): 488 (5,91%) <36 and 296
      (19,83%) >36. The most recent first trimester screen test, which have been
      involved in the laboratory since April 2010 detected 7 (0,84%) and 23 (13,45%)
      women respectively to the age groups with increased risk for a chromosome
      disease. Additional ultrasonographic scan confirmed the biochemical risk for a
      serious Neural Tube/Abdomainal Wall defects in 5 out of 32 fetuses with increased
      risk for these defects; other 3 fetuses were detected to be involuntary
      miscarried as "missed abortion", 1 triploidy included. We comment on the
      sensitivity, limitations and the stepwise sequential testing way of achieving a
      high performance of screening for chromosome diseases based on preliminary
      information to pregnant women on different options for a contemporary approach
      for genetic prevention.

PMID- 22639775
TI  - [18F-FDG PET/CT in patients, treated for ovarian cancer, with elevated CA 125
      levels but no evidence of recurrence on conventional imaging].

PMID- 22639776
TI  - [Pregnancy and oncological diseases].
AB  - AIM: The oncological diseases during pregnancy are very rare, but the incidence
      rate is constantly increasing. The diagnosis and treatment of the cancer during
      pregnancy are connected with the risk of the diagnostic procedures on the foetus
      and the risk of the treatment methods upon the developing foetus. That is why we
      decided to assess and research our and foreign experience in this field. MATERIAL
      AND METHODS: We performed a retrospective research work in this field. For 10
      years period we examined: -20 patients with precancer and cancer of the vulva
      combined with pregnancy -70 patients with cervical cancer and pregnancy -30
      patients with ovarian cancer and pregnancy -60 patients with breast cancer and
      pregnancy The most important point in the diagnosis and treatment of the
      oncological diseases connected with pregnancy is not to delay the treatment of
      the pregnant woman. RESULTS: The patients with early stages of the cervical
      cancer connected with pregnancy are treated conservatively. The patients with
      invasive cervical cancer and pregnancy-the gestational age and the wish of the
      patient to have a baby are the main factors formulating the kind of treatment. In
      early 1-st and II-nd trimester the patients with IB and IIA stage are treated
      with radical hysterectomy together with the foetus or the standard chemo
      radiotherapy. Advanced cervical cancer-IB2-II stage. In these patients pelvic
      radiotherapy with chemotherapy is used if the cancer is diagnosed in the first 20
      gestational weeks. Acording to us and the most foreign authors the adnexal masses
      must be eradicated surgically in the II-nd trimester of the pregnancy (13-16
      gestational weeks). The most ovarian cancers are in early stage and chemotherapy
      may be delayed after the delivery especially for epithelial tumors I-st stage.
      DISCUSSION: In precancer and cancer of the uterine cervix as well as in all other
      oncogynaecological and oncological diseases combined with pregnancy we offer 2
      algorithms to be used. CONCLUSION: The oncolgical types of treatment including
      surgery, chemotherapy and radiotherapy(with exception of radiotherapy for small
      pelvis and abdominal cavity) may safely be applied after the I-st trimester of
      the pregnancy.

PMID- 22639777
TI  - [Extraperitoneal lymph node dissection in cervical cancer patients].
AB  - AIM: Extraperitoneal lymph node dissection (EPLD) has been performed in 14
      patients with invasive cervical cancer. The technique of EPLD has been described
      and presented as well as its feasibility, especially as staging procedure in
      locally advanced stages of cervical cancer.

PMID- 22639778
TI  - [Drug therapy for diabetes mellitus during pregnancy and breastfeeding in the
      beginning of 21 century: status quo and new challenges].
AB  - Diabetes mellitus is frequent during pregnancy and is associated with substantial
      risks both for the mother and the newborn. An adequate therapy ensures the normal
      course of pregnancy and delivery and postnatal development of the baby. Insulin,
      for its well known safety record, has long been considered the drug of first
      choice for achieving optimal glycemic control in pregnant women. Pregnancy is an
      indication for intensive insulin therapy. The pre-mixed insulins are not
      recommended due to their inability to provide the needed therapeutic flexibility
      during the different periods of pregnancy. The short acting insulin analogue
      aspart is currently registered for meal-time use in basal therapy with NPH
      insulin. The long-acting analogues glargine and detemir are still investigated
      clinically and for the moment are only used off label in pregnancy. Maternal
      hypoglycemia, the need of injection and the high cost are the main drawbacks of
      insulin therapy. Evidence has accumulated in recent years that some oral
      antidiabetics are as efficacious and safe as insulin in gestational diabetes.
      Metformin and glibenclamide are now increasingly viewed as a rational alternative
      to insulin therapy--a treatment both preferred by the women and a less expensive
      one, during pregnancy and breastfeeding.

PMID- 22639779
TI  - [Transversal vaginal septum in two months old patient--case report].
AB  - The current publication describes a case of a two months old girl with a
      transverse vaginal septum presented. The clinical debut is with a large
      hydromucocolpos. It is concomitantly presented with a bilateral postaxial
      polydactyly of the upper limbs, typical for McKusick-Kaufmann syndrome.

PMID- 22639780
TI  - [Surgical treatment of locally advanced vulvar cancer: report on two cases].
AB  - The aim of the study was to define the notion of locally advanced vulvar cancer
      (LAVC) and approaches to treatment by presenting clinical cases encountered by
      the authors. MATERIALS AND METHODS: The clinical cases described present
      different views on therapeutic approaches to cases with LAVC. Apart from cases of
      primary advanced vulvar cancer, there exist cases, in which primary treatment was
      applied. In such cases, however, involvement of adjacent structures was a result
      from recurrence of the disease. LAVC implies that the primary or recurrent tumour
      cannot be treated solely by radical removal of the vulva. Modem treatment of LAVC
      include ultraradical surgery, radiotherapy, chemoradiotherapy, or a combination
      of these methods. Studies have confirmed the hypothesis that megovoltage
      radiotherapy can yield a significant regression of LAVC that makes it possible to
      apply more sparing surgical resections and preserve the functions of adjacent
      organs, thus improving life quality. CONCLUSION: Surgical treatment of LAVC
      without preoperative chemoradiotherapy is recommendable only in cases of
      resectable tumours, possibly with non-metastatic and primarily resectable
      regional lymph nodes.

PMID- 22639781
TI  - [Postoperatively conformed effectiveness of preoperative radio therapy, combined
      with chemotherapy - cysplatin].
AB  - The authors present a case of a 35 years old female patient with spinocellular
      carcinoma of the cervix, diagnosed after byopsy and treated with radiotherapy 30
      Gray, combined with Cisplatin 50 mg. per square meter, per week, 6 months before
      radical histerectomy and lymphonodulectomy was performed. The postoperative
      histology shows only traces of dysplastic epithelia, which proves preoperative
      therapy effective.

PMID- 22639783
TI  - [Contribution to the development of the program in ObGyn for medical students].

PMID- 22639782
TI  - [HPV-associated verrucous carcinoma of the perianal region--complete remission
      after surgical excision and postoperative monochemotherapy with methotrexat].
AB  - Verrucous carcinoma of the perianal area continues still to be rare finding,
      which in histopathological aspect is a highly differentiated form of squamous
      cell carcinoma. Many literature data show that it is quite possible that HPV
      viruses play probably a key role in the etiology of verrucous carcinoma. We
      present a case of 48 year-old female patient with verrucous carcinoma localized
      in the perianal area, treated initially under the diagnosis of perianal skin
      tags, while surgical removal of the lesion was found rare form of HPV associated
      verrucous carcinoma. A preventive mono-chemotherapy with methotrexate by scheme
      was started for an initial period of 3 months. Six months later, the provided
      monitoring has not shown clinical or apparative data on tumor recurrence. The
      article discusses key points of the diagnostic algorithm in patients with HPV
      associated lesions with anogenital localization and provides valuable
      recommendations for correct clinical behavior in these risk groups.

PMID- 22639784
TI  - [Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical
      intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double
      blind PATRICIA trial].

PMID- 22639785
TI  - Efficient stabilization of phosphodiester (PO), phosphorothioate (PS), and 2'-O
      methoxy (2'-OMe) DNA.RNA hybrid duplexes by amino sugars.
AB  - Antisense strategies that target DNA.RNA hybrid structures offer potential for
      the development of new therapeutic drugs. The alpha-sarcin loop region of the 23S
      [corrected] rRNA domain has been shown to be a high value target for such
      strategies. Herein, aminoglycoside interaction with three RNA.DNA alpha-sarcin
      targeted duplexes (rR.dY, rR.S-dY, and rR.2'OMe-rY) have been investigated to
      determine the overall effect of aminoglycoside interaction on the stability,
      affinity, and conformation of these hybrid duplexes. To this end, UV thermal
      denaturation, circular dichroism spectroscopy, fluorescence intercalator
      displacement, and ITC as well as DSC calorimetry experiments were carried out.
      The results suggest the following. (1) Of all the aminoglycosides studied,
      neomycin confers the highest thermal stability on all three hybrid duplexes
      studied. (2) There is no appreciable difference in aminoglycoside-induced thermal
      stability between the unmodified rR.dY and phophorothioate modified rR.S-dY
      duplexes. (3) The rR.2'OMe-rY duplexes thermal stability is slightly less than
      the other two hybrids. (4) In all three duplexes, aminoglycoside-induced thermal
      stability decreased as the number of amino groups decreased. (5) CD scans
      revealed similar spectra for the rR.dY and rR.S-dY duplexes as well as a more
      pronounced A-form signal for the rR.2'OMe-rY duplex. (6) FID assays paralleled
      the CD results, yielding similar affinity values between the rR.dY and rR.S-dY
      duplexes and higher affinities with the rR.2'OMe-rY duplex. (7) The overall
      affinity trend between aminoglycosides and the three duplexes was determined to
      be neomycin > paromomycin > neamine > ribostamycin. (8) ITC K(a) values revealed
      similar binding constants for the rR.dY and rR.S-dY duplexes with rR.dY having a
      K(1) of (1.03 +/- 0.58) * 10(7) M(-1) and K(2) of (1.13 +/- 0.07) * 10(5) M(-1)
      while rR.S-dY produced a K(1) of (1.17 +/- 0.54) * 10(7) M(-1) and K(2) of (1.27
      +/- 0.69) * 10(5) M(-1). (8) The rR.2'OMe-rY produced a slightly higher binding
      constant values with a K(1) of (1.25 +/- 0.24) * 10(7) M(-1) and K(2) of (3.62 +/
      0.18) * 10(5) M(-1). (9) The DeltaT(m)-derived K(Tm) of 3.81 * 10(7) M(-1) for
      rR.S-dY was in relative agreement with the corresponding K(1) of 1.17 * 10(7) M(
      1) derived constant from the fitted ITC. These results illustrate that the
      increased DNA.RNA hybrid duplex stability in the presence of aminoglycosides can
      help extend the roles of aminoglycosides in designing modified ODNs for targeting
      RNA.

PMID- 22639786
TI  - Tertiary prophylaxis in adults: is there a rationale?
AB  - There is lack of evidence-based recommendations or clear-cut consensus regarding
      the clinical and economic utility of regular prophylaxis started in adulthood,
      with the aim of keeping the clinical situation from getting worse by prevention
      of further bleeds contributing to increasing musculo-skeletal or other morbidity
      in haemophilia. Such a prophylaxis program has been shown in relatively small
      cohorts to be effective in reducing bleeding occurrence, with a variable effect
      on the joint status, but with significantly higher factor consumption and
      consequently higher costs than on-demand therapy. There has been no attempt to
      identify subsets of patients who may benefit from "tertiary" prophylaxis more
      than others, for example, due to their bleeding phenotype and/or requirements for
      product issued on-demand or to identify the dosage that provides the optimal
      balance of clinical benefit and cost effectiveness. This article reviews the
      published literature on prophylaxis started beyond the age of 18 years, the
      barriers to the uptake of prophylaxis programs particularly in adults and
      highlights areas in need of further research.

PMID- 22639787
TI  - Interlaboratory reproducibility of selective reaction monitoring assays using
      multiple upfront analyte enrichment strategies.
AB  - Over the past few years, mass spectrometry has emerged as a technology to
      complement and potentially replace standard immunoassays in routine clinical core
      laboratories. Application of mass spectrometry to protein and peptide measurement
      can provide advantages including high sensitivity, the ability to multiplex
      analytes, and high specificity at the amino acid sequence level. In our previous
      study, we demonstrated excellent reproducibility of mass spectrometry-selective
      reaction monitoring (MS-SRM) assays when applying standardized standard operating
      procedures (SOPs) to measure synthetic peptides in a complex sample, as lack of
      reproducibility has been a frequent criticism leveled at the use of mass
      spectrometers in the clinical laboratory compared to immunoassays. Furthermore,
      an important caveat of SRM-based assays for proteins is that many low-abundance
      analytes require some type of enrichment before detection with MS. This adds a
      level of complexity to the procedure and the potential for irreproducibility
      increases, especially across different laboratories with different operators. The
      purpose of this study was to test the interlaboratory reproducibility of SRM
      assays with various upfront enrichment strategies and different types of clinical
      samples (representing real-world body fluids commonly encountered in routine
      clinical laboratories). Three different, previously published enrichment
      strategies for low-abundance analytes and a no-enrichment strategy for high
      abundance analytes were tested across four different laboratories using different
      liquid chromatography-SRM (LC-SRM) platforms and previously developed SOPs. The
      results demonstrated that these assays were indeed reproducible with coefficients
      of variation of less than 30% for the measurement of important clinical proteins
      across all four laboratories in real world samples.

PMID- 22639788
TI  - Endothelial dysfunction, increased inflammation, and activated coagulation in HIV
      infected patients improve after initiation of highly active antiretroviral
      therapy.
AB  - OBJECTIVES: Endothelial dysfunction and inflammation have been demonstrated to be
      markers of cardiovascular risk. We investigated the effects of HIV infection per
      se and the antiretroviral treatment prescribed on the levels of risk factors of
      cardiovascular disease. METHODS: This was a prospective study of 20 treatment
      naive, nonsmoking, HIV-positive patients examined before and after 3 months of
      treatment with a protease inhibitor (PI)-containing regimen followed by 3 months
      of treatment with nonnucleoside reverse transcriptase inhibitor (NNRTI)
      containing therapy. Parameters of inflammation, endothelial function and
      coagulation were examined. The results were compared with those for an age- and
      gender-matched, nonsmoking, healthy control group. RESULTS: Compared with
      controls, treatment-naive HIV-infected patients exhibited endothelial dysfunction
      [flow-mediated dilation (FMD) 108 vs. 111% for HIV-infected vs. control groups,
      respectively; P < 0.05] and activation [von Willebrand factor 2.0 vs. 0.9 U/l;
      soluble intercellular adhesion molecule (sICAM) 313 vs. 211 ng/L, respectively; P
      < 0.01]. Inflammation [C-reactive protein (CRP) 24 vs. 8.6 nmol/L; fibrinogen 9.4
      vs. 8.6 MUmol/L, respectively; P < 0.05] and coagulation/fibrinolysis (D-dimers
      0.55 vs. 0.23 MUg/mL, respectively; P < 0.01) were increased. Initiating therapy
      resulted in normalization of FMD and a significant decrease in endothelial
      activation and CRP. CONCLUSION: Endothelial dysfunction together with increased
      inflammation and coagulation were more prevalent in untreated HIV-infected
      patients compared with controls. These cardiovascular risk factors improved with
      treatment, although not all parameters normalized after 6 months.

PMID- 22639789
TI  - Exploiting structural information in patent specifications for key compound
      prediction.
AB  - Patent specifications are one of many information sources needed to progress drug
      discovery projects. Understanding compound prior art and novelty checking,
      validation of biological assays, and identification of new starting points for
      chemical explorations are a few areas where patent analysis is an important
      component. Cheminformatics methods can be used to facilitate the identification
      of so-called key compounds in patent specifications. Such methods, relying on
      structural information extracted from documents by expert curation or text
      mining, can complement or in some cases replace the traditional manual approach
      of searching for clues in the text. This paper describes and compares three
      different methods for the automatic prediction of key compounds in patent
      specifications using structural information alone. For this data set, the cluster
      seed analysis described by Hattori et al. (Hattori, K.; Wakabayashi, H.; Tamaki,
      K. Predicting key example compounds in competitors' patent applications using
      structural information alone. J. Chem. Inf. Model.2008, 48, 135-142) is superior
      in terms of prediction accuracy with 26 out of 48 drugs (54%) correctly predicted
      from their corresponding patents. Nevertheless, the two new methods, based on
      frequency of R-groups (FOG) and maximum common substructure (MCS) similarity
      measures, show significant advantages due to their inherent ability to visualize
      relevant structural features. The results of the FOG method can be enhanced by
      manual selection of the scaffolds used in the analysis. Finally, a successful
      example of applying FOG analysis for designing potent ATP-competitive AXL kinase
      inhibitors with improved properties is described.

PMID- 22639790
TI  - Implications of perceived physical and social aspects of the environment for self
      reported physical and mental health.
AB  - The purpose of the present study is to explore the relative importance of certain
      socio-demographic variables, perceived physical and social attributes of the home
      and neighborhood for self-reported physical and mental health. The sample of the
      present study comprised 137 men and women (51.83% women and 48.17% men) ranging
      in age from 26 to 54 years selected randomly from shoppers visiting a crowded
      shopping plaza. A sociodemographic data sheet, scales to measure perceptions of
      the physical environment and neighborhood characteristics, and the SF-36 to
      assess physical and mental health components were used. Data were analyzed using
      multivariate analyses of variance, Pearson's correlation coefficients and
      multiple regression analysis. No age and gender differences in physical and
      mental health scores emerged (p < 0.05), but people who perceived their socio
      economic status as low also reported lower total mental health scores (p < 0.05).
      No socioeconomic differences were noted on indices of physical health (p > 0.05).
      Correlation analysis revealed that negative perceptions of the interior home
      environment were associated negatively with physical and mental health scores (p
      < 0.05). Regression analysis indicated that perceived decay and disorganization
      in the home interior as well as perceived socioeconomic status accounted for a
      significant portion of the variance in mental health scores.

PMID- 22639792
TI  - Natural variation in the temperature range permissive for vernalization in
      accessions of Arabidopsis thaliana.
AB  - Vernalization is an acceleration of flowering in response to chilling, and is
      normally studied in the laboratory at near-freezing (2-4  degrees C)
      temperatures. Many vernalization-requiring species, such as Arabidopsis thaliana,
      are found in a range of habitats with varying winter temperatures. Natural
      variation in the temperature range that elicits a vernalization response in
      Arabidopsis has not been fully explored. We characterized the effect of
      intermediate temperatures (7-19  degrees C) on 15 accessions and the well-studied
      reference line Col-FRI. Although progressively warmer temperatures are gradually
      less effective at activating expression of the vernalization-specific gene
      VERNALIZATION-INSENSITIVE 3 (VIN3) and in accelerating flowering, there is
      substantial natural variation in the upper threshold (T(max) ) of the flowering
      time response. VIN3 is required for the T(max)  (13  degrees C) response of Col
      FRI. Surprisingly, even 16  degrees C treatment caused induction of VIN3 in six
      tested lines, despite the ineffectiveness of this temperature in accelerating
      flowering for two of them. Finally, we present evidence that mild acceleration of
      flowering by 19  degrees C exposure may counterbalance the flowering time delay
      caused by non-inductive photoperiods in at least one accession, creating an
      appearance of photoperiod insensitivity.

PMID- 22639793
TI  - Chlorhexidine-associated transient hyperchloremia in an infant.
AB  - An infant was cleansed with 2% clorhexidine gluconate (CHG) because of repeated
      sepsis episodes from skin colonization. Asymptomatic hyperchloremia ensued, most
      likely associated with CHG therapy. Fourty-eight hours after CHG therapy
      withdrawal, serum chloride levels returned to normal. Hyperchloremia may be a
      reversible adverse effect of extensive use of CHG.

PMID- 22639794
TI  - Hypermobility and musculoskeletal pain in children: a systematic review.
AB  - OBJECTIVE: To examine the evidence of an association between hypermobility and
      musculoskeletal pain in children. METHODS: A systematic review of the literature
      was performed using the databases PubMed, EMBASE, NHS Evidence, and Medline.
      Inclusion criteria were observational studies investigating hypermobility and
      musculoskeletal pain in children. Exclusion criteria were studies conducted on
      specialist groups (i.e. dancers) or hospital referrals. Pooled odds ratios (ORs)
      were calculated using random effects models and heterogeneity was tested using
      chi(2)-tests. Study quality was assessed using the Newcastle-Ottawa Scale for
      case-control studies. RESULTS: Of the 80 studies identified, 15 met the inclusion
      criteria and were included in the review. Of these, 13 were included in the
      statistical analyses. Analysing the data showed that the heterogeneity was too
      high to allow for interpretation of the meta-analysis (I(2) = 72%). Heterogeneity
      was much lower when the studies were divided into European (I(2) = 8%) and Afro
      Asian subgroups (I(2) = 65%). Sensitivity analysis based on data from studies
      reporting from European and Afro-Asian regions showed no association in the
      European studies [OR 1.00, 95% confidence interval (CI) 0.79-1.26] but a marked
      relationship between hypermobility and joint pain in the Afro-Asian group (OR
      2.01, 95% CI 1.45-2.77). Meta-regression showed a highly significant difference
      between subgroups in both meta-analyses (p < 0.001). CONCLUSION: There seems to
      be no association between hypermobility and joint pain in Europeans. There does
      seem to be an association in Afro-Asians; however, there was a high
      heterogeneity. It is unclear whether this is due to differences in ethnicity,
      nourishment, climate or study design.

PMID- 22639795
TI  - Real-time PCR optimization to identify environmental  Vibrio spp. strains.
AB  - AIMS: To identify Vibrio vulnificus, Vibrio cholerae and Vibrio alginolyticus
      using standardized DNA extraction method and real-time PCR assays, among a large
      number of bacterial strains isolated from marine environment. METHODS AND
      RESULTS: Methods for DNA extraction and real-time PCR were standardized to
      identify a large number of Vibrio spp. strains isolated through regular
      collection campaigns of environmental samples. Three real-time PCR assays were
      developed from a multiplex PCR, targeting V. vulnificus, V. cholerae and V.
      alginolyticus on the dnaJ gene. After testing their specificity, these systems
      were applied for the identification of 961 strains isolated at 22 degrees C (446
      strains) and 37 degrees C (515 strains) in September 2009. The predominance of V.
      alginolyticus (82.6%) among the Vibrio spp. strains isolated at 37 degrees C was
      shown. At 22 degrees C, only 1.6% of the strains were identified by PCR and they
      were V. alginolyticus. CONCLUSIONS: Reproducible and specific real-time PCR
      assays combined to a DNA extraction method on microplates were used to constitute
      a large environmental Vibrio strains collection and to identify and detect
      potential human pathogenic Vibrio isolated at 37 degrees C. For environmental
      strains isolated at 22 degrees C, because of the higher species diversity, other
      approaches, like sequencing, should be chosen for identification. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The protocol developed in this study provides an
      appropriate and rapid screening tool to identify a large number of bacterial
      strains routinely isolated from the environment in long-term studies.

PMID- 22639796
TI  - Linking visual response properties in the superior colliculus to saccade
      behavior.
AB  - Here we examined the influence of the visual response in the superior colliculus
      (SC) (an oculomotor control structure integrating sensory, motor and cognitive
      signals) on the development of the motor command that drives saccadic eye
      movements in monkeys. We varied stimulus luminance to alter the timing and
      magnitude of visual responses in the SC and examined how these changes correlated
      with resulting saccade behavior. Increasing target luminance resulted in multiple
      modulations of the visual response, including increased magnitude and decreased
      response onset latency. These signal modulations correlated strongly with changes
      in saccade latency and metrics, indicating that these signal properties carry
      through to the neural computations that determine when, where and how fast the
      eyes will move. Thus, components of the earliest part of the visual response in
      the SC provide important building blocks for the neural basis of the sensory
      motor transformation, highlighting a critical link between the properties of the
      visual response and saccade behavior.

PMID- 22639797
TI  - "Remember the bubbles hurt you when you cook in the pan": young children's views
      of illness causality.
AB  - The present study examines four-year-old children's everyday understandings of
      illness causality. Research into young children's conceptualisation of illness
      has led to different expectations of children's comprehension and ongoing debate
      regarding the nature of children's knowledge. Awareness of preschoolers'
      spontaneous views of illness causality, rather than explanations restricted by
      predetermined response categories, is likely to assist practitioners to provide
      more appropriate interventions for young children. Adopting a socio
      constructivist perspective of children's learning and development, and using a
      narrative methodology, we interviewed five preschoolers regarding their views of
      illness causality. As part of the interview process children were invited to
      construct their own storybooks about illness using photographs of children
      experiencing illness and a variety of art materials. Analysis of young children's
      narrative accounts revealed two major threads regarding children's illness
      causality constructions: (1) "behaviour-based explanations for illness", and (2)
      "illness prevention messages and behavioural rules". Findings suggest that four
      year-olds' understanding may be more sophisticated than traditionally maintained,
      and that the illness prevention messages and behavioural rules within
      sociocultural contexts may significantly influence children's conceptualisation
      of illness causality.

PMID- 22639800
TI  - Combined surgical therapy of peri-implantitis evaluating two methods of surface
      debridement and decontamination. A two-year clinical follow up report.
AB  - OBJECTIVES: The study aimed at evaluating the 2-year results obtained following
      combined surgical resective and regenerative treatment of advanced peri
      implantitis defects comparing two methods of surface debridement/decontamination
      (DD). MATERIAL & METHODS: Twenty-four patients (n = 26 combined supra- and
      intrabony defects) completed the 24 months follow-up observation following access
      flap surgery, granulation tissue removal and implantoplasty at bucally and
      supracrestally exposed implant parts. The remaining aspects were randomly
      allocated to surface DD using either (i) an Er:YAG laser (ERL) device, or (ii)
      plastic curets + cotton pellets + sterile saline (CPS) were augmented with a
      natural bone mineral and covered with a collagen membrane. RESULTS: At 24 months,
      ERL treated sites failed to reveal significantly higher reductions in mean BOP
      (ERL: 75.0 +/- 32.6% versus CPS: 54.9 +/- 30.3%) and CAL values (ERL: 1.0 +/- 2.2
      mm versus CPS: 1.2 +/- 2.2 mm) when compared with the CPS group. In both groups,
      mean CAL values were not significantly different when compared with baseline.
      CONCLUSION: The long-term stability of clinical outcomes obtained following
      combined surgical therapy of advanced peri-implantitis may be influenced by
      factors other than the method of surface debridement/decontamination.

PMID- 22639799
TI  - Which providers can bridge the health literacy gap in lifestyle risk factor
      modification education: a systematic review and narrative synthesis.
AB  - BACKGROUND: People with low health literacy may not have the capacity to self
      manage their health and prevent the development of chronic disease through
      lifestyle risk factor modification. The aim of this narrative synthesis is to
      determine the effectiveness of primary healthcare providers in developing health
      literacy of patients to make SNAPW (smoking, nutrition, alcohol, physical
      activity and weight) lifestyle changes. METHODS: Studies were identified by
      searching Medline, Embase, Cochrane Library, CINAHL, Joanna Briggs Institute,
      Psychinfo, Web of Science, Scopus, APAIS, Australian Medical Index, Community of
      Science and Google Scholar from 1 January 1985 to 30 April 2009. Health literacy
      and related concepts are poorly indexed in the databases so a list of text words
      were developed and tested for use. Hand searches were also conducted of four key
      journals. Studies published in English and included males and females aged 18
      years and over with at least one SNAPW risk factor for the development of a
      chronic disease. The interventions had to be implemented within primary health
      care, with an aim to influence the health literacy of patients to make SNAPW
      lifestyle changes. The studies had to report an outcome measure associated with
      health literacy (knowledge, skills, attitudes, self efficacy, stages of change,
      motivation and patient activation) and SNAPW risk factor.The definition of health
      literacy in terms of functional, communicative and critical health literacy
      provided the guiding framework for the review. RESULTS: 52 papers were included
      that described interventions to address health literacy and lifestyle risk factor
      modification provided by different health professionals. Most of the studies
      (71%, 37/52) demonstrated an improvement in health literacy, in particular
      interventions of a moderate to high intensity.Non medical health care providers
      were effective in improving health literacy. However this was confounded by
      intensity of intervention. Provider barriers impacted on their relationship with
      patients. CONCLUSION: Capacity to provide interventions of sufficient intensity
      is an important condition for effective health literacy support for lifestyle
      change. This has implications for workforce development and the organisation of
      primary health care.

PMID- 22639801
TI  - Primary human endothelial cells secrete agents that reduce responsiveness to
      lysophosphatidic acid (LPA).
AB  - The plasma level of LPA (lysophosphatidic acid) (200-600 nM) is well within the
      range that promotes proliferation and migration of vascular ECs (endothelial
      cells), yet vessels are quiescent and stable. In this report, we considered one
      explanation for this paradox: that ECs secrete agents that attenuate
      responsiveness to LPA. Indeed, we observed that CM (conditioned medium) from
      confluent, quiescent cultures of primary HUVECs (human umbilical vein ECs)
      contained an agent that inhibited LPA-mediated signalling events and cellular
      responses. The putative inhibitor, which we tentatively call ILMR (inhibitor of
      LPA-mediated responsiveness) seemed to act on cells (instead of at the level of
      LPA) by suppressing the ability of LPA receptor 1 to signal. The amount and/or
      activity of ILMR was regulated by growth factors; exposing HUVECs to VEGF-A
      (vascular endothelial growth factor A), but not bFGF (basic fibroblast growth
      factor), reduced the amount and/or activity of ILMR in CM. We conclude that in
      addition to promoting angiogenesis directly, VEGF-A can also act indirectly by
      modulating the bioactivity of angiomodulators such as LPA.

PMID- 22639803
TI  - Sex recognition and mate choice by male Bufo gargarizans in central China.
AB  - Mate choice is important for successful reproduction, and consequently species
      have evolved various ways to choose potential high-quality mates. Anuran mate
      choice and underlying processes have been the subject of several recent
      investigations, however we are far from a complete understanding of mate choice
      in this system. In the present study, when given a simultaneous choice between a
      male and a female of identical size, males did not discriminate between the
      sexes, and attempted to clasp a male or a female with equal frequency. Test males
      only released the stimulus toad when a release call was emitted by the stimulus
      male. When two males with distinct size differences were provided with a male,
      the male chose the larger one. Moreover, males discriminated between gravid
      females that differed in body size, choosing larger gravid females over smaller
      ones. These results suggest that male Bufo gargarizans can discriminate between
      the sexes, probably based on male release calls, and prefer to mate with larger
      individual using visual cues.

PMID- 22639802
TI  - "Burden of osteoporotic fractures in primary health care in Catalonia (Spain): a
      population-based study".
AB  - BACKGROUND: Knowledge on the epidemiology of non-hip fractures in Spain is
      limited and somewhat outdated. Using computerized primary care records from the
      SIDIAP database, we derived age and sex-specific fracture incidence rates for the
      region of Catalonia during the year 2009. METHODS: The SIDIAP database contains
      quality-checked clinical information from computerized medical records of a
      representative sample of >5,800,000 patients (80% of the population of
      Catalonia). We conducted a retrospective cohort study including all patients aged
      >=50 years, and followed them from January 1 to December 31, 2009. Major
      osteoporotic fractures registered in SIDIAP were ascertained using ICD-10 codes
      and validated by comparing data to hospital admission and patient-reported
      fractures records. Incidence rates and 95% confidence intervals were calculated.
      RESULTS: In total, 2,011,430 subjects were studied (54.6% women). Overall
      fracture rates were 10.91/1,000 person-years (py) [95%CI 10.89-10.92]:
      15.18/1,000 py [15.15-15.21] in women and 5.78/1,000 py [5.76-5.79] in men. The
      most common fracture among women was wrist/forearm (3.86/1,000 py [3.74-3.98]),
      while among men it was clinical spine (1.25/1,000 py [1.18-1.33]). All fracture
      rates increased with age, but varying patterns were observed: while most of the
      fractures (hip, proximal humerus, clinical spine and pelvis) increased
      continuously with age, wrist and multiple rib fractures peaked at age 75-80 and
      then reached a plateau. CONCLUSIONS: Our study provides local estimates of age,
      sex and site-specific fracture burden in primary health care, which will be
      helpful for health-care planning and delivery. A proportion of fractures are not
      reported in primary care records, leading to underestimation of fracture
      incidence rates in these data.

PMID- 22639804
TI  - Distributional change and epidemic introgression in overlapping areas of Japanese
      pond frog species over 30 years.
AB  - Pelophylax nigromaculatus, P. porosus porosus, and P. p. brevipoda are three pond
      frog species distributed in Japan. Their distributions overlap at two basins in
      central Japan (P. nigromaculatus and P. p. porosus in the Matsumoto basin, and P.
      nigromaculatus and P. p. brevipoda in the Ina basin), and hybrid descendants have
      been found in these areas. To clarify the distribution areas and hybrid zones of
      the frogs, and to understand the mode of introgressive hybridization and its
      impact on the frog populations, we conducted exhaustive sampling at each basin
      and performed allozyme and mtDNA analyses of 233 individuals. Analysis using
      genetic markers clearly detected nine F1 hybrids and 94 hybrid descendants of P.
      nigromaculatus and P. porosus from the overlapping areas of both basins. Allozyme
      and mtDNA data suggest directional hybridization between female P. p. porosus and
      male P. nigromaculatus in the Matsumoto basin. Over the past 30 years, the
      distribution of P. p. porosus has been narrowed and fragmented by the invasion of
      P. nigromaculatus, seemingly because of directional hybridization in the
      Matsumoto basin. In the Ina basin, the "pure" P. p. brevipoda (n = 8) population
      was extremely reduced by gene introgression from P. nigromaculatus, yet its
      distribution was barely changed compared to the Matsumoto basin. Consequently,
      this study shows that P. porosus populations are threatened by interspecific
      hybridization with P. nigromaculatus, and that introgressive hybridization
      damaged P. porosus populations by different means in each basin.

PMID- 22639805
TI  - Hidden diversity in a reef-dwelling sea slug, Pteraeolidia ianthina
      (Nudibranchia, Aeolidina), in the Northwestern Pacific.
AB  - The population genetic structure of a reef-dwelling aeolid nudibranch,
      Pteraeolidia ianthina ( Angas, 1864 ) (Gastropoda, Mollusca), was investigated by
      analyzing the nuclear ribosomal RNA gene region, including 18S and 5.8S rRNA
      genes and the ITS1 region (545 bp). Among 235 individuals from 10 localities in
      the northwestern Pacific, two genetically distinct groups were detected: Groups A
      and B, which are separated by a minimum sequence difference of 5.3% (p-distance).
      The marked genetic differentiation of these two groups, even in localities where
      both co-occur, suggests that they are distinct species, although intergroup
      hybrids were observed in very low frequency. Within-population genetic
      variability was low in Group A, but high in Group B. Geographic analysis of
      between-population genetic distance and "allele" sharing data indicated three
      subgroups within Group A (temperate Japan, Ryukyus + Philippines, and Guam),
      whose distribution ranges appear to have some relationship to climate zones
      (temperate and subtropics + tropics) and ocean currents (Kuroshio and North
      Equatorial Currents). Within Group B detected only from three subtropic and
      tropic localities, however, genetic distances between populations were much
      smaller than those in Group A, and thus no significant geographic pattern was
      found. These differences in genetic variability and population structure between
      Groups A and B may reflect differences in biological features between them, such
      as the duration of the pelagic larval stage. Furthermore, some morphological
      differences were observed between Groups A and B. These observations provide
      further support for the suggestion that the two groups are separate species.

PMID- 22639806
TI  - Testis asymmetry and sperm length in Rhacophorus omeimontis.
AB  - Theory predicts that the degree of testes asymmetry should be positively
      correlated with male body condition in species with directional testis asymmetry.
      We tested this prediction in Rhacophorus omeimontis, a species in which females
      mate with more than one male. Our results showed that the treefrogs did not
      exhibit the absence of directional asymmetry in testis size, but rather the
      occurrence of fluctuating asymmetry. Moreover, we also tested differences in body
      size, body mass, testis mass, testis asymmetry, and sperm size among initially
      paired, jointly paired, and unpaired males. We found that body size and mass,
      testis mass, testis asymmetry and sperm length did not differ among the three
      male types. Testis mass showed a positive relationship with soma mass, but the
      correlations between the extent of fluctuating testis asymmetry and sperm length,
      and between testis mass and sperm length were not significant. Our data suggest
      that testes size and sperm length do not play an important role in determining
      male mating success in the presence of sperm competition.

PMID- 22639807
TI  - The application of temperature data loggers for remotely monitoring the nests of
      Emei Shan Liocichla (Liocichla omeiensis).
AB  - Temperature data loggers (TDL) are mostly used to monitor avian incubation
      behavior in bird studies. In this paper we demonstrate how TDL can also be used
      to determine different breeding stages and nest success of the vulnerable Emei
      Shan Liocichla (Liocichla omeiensis). All nests that contained at least one egg
      were divided into two groups. Group I included six nests monitored traditionally
      by the observers' visits, while Group II included eight nests monitored by TDL.
      Group I and Group II were visited every 1-4 days and 7 days, respectively, to
      check nest contents and status (e.g., active vs. inactive, and the breeding
      process) until fledging or nest failure. The time of each observation was
      recorded to verify the interpretation of TDL. The data recorded by TDL were
      converted into line graphs of temperature against time and assessed visually. The
      results indicated that TDL can reliably identify different breeding stages and
      estimate daily nest survival rates (DSR) and total nest success. The nest success
      of Group II (0.3015) was higher than that of Group I (0.2387), suggesting that
      deployment of TDL did not negatively influence nest survival rate of Emei Shan
      Liocichla. In contrast to traditional nest visits, TDL minimized disturbance by
      observers and provided a more precise estimate of nest survival. We suggest that
      TDL should be used more widely in studies of the breeding ecology of rare and
      endangered birds.

PMID- 22639808
TI  - Transforming growth factor-alpha mRNA expression and its possible roles in mouse
      endometrial stromal cells.
AB  - Transforming growth factor-alpha (TGFalpha) is thought to be involved in the
      regulation of endometrial cells. We investigated Tgfa mRNA expression, and the
      effects of TGFalpha on DNA-synthesis and gene expression of insulin-like growth
      factor 1 (IGF1), IGF binding protein-3 (IGFBP3) and IGF1 receptor in the mouse
      endometrial cells, because IGF1 is involved in estrogen-induced growth of
      endometrial cells. We also investigated the role of TGFalpha on matrix
      metalloproteinase (MMP) expression, as MMPs are involved both in tissue
      remodeling during cell proliferation and in enhancement of IGF1 signaling through
      the degradation of IGFBP3. Tgfa mRNA expression was detected in endometrial
      luminal and glandular epithelial cells, and stromal cells. Tgfa mRNA signals did
      not appear to change in endometrial luminal epithelial cells, but signals in
      glandular epithelial cells were higher at diestrus 1, 2 and proestrus, and the
      number of stromal cells showing strong signals appeared to increase at diestrus 1
      and 2. Endometrial epithelial and stromal cells were treated with estradiol
      17beta (E2) or progesterone (P4). E2 or P4 stimulated Tgfa mRNA expression in
      stromal cells. TGFalpha stimulated DNA synthesis in endometrial epithelial and
      stromal cells, while E2 and P4 stimulated DNA synthesis in stromal cells. In
      stromal cells, TGFalpha, at as low as 1 ng/ml, decreased Igfbp3 and Mmp9 mRNA
      levels, while high dose (10 ng/ml) of TGFalpha decreased Igf1 mRNA level and
      increased Mmp3 mRNA level. These results imply that TGFalpha stimulates
      proliferation of endometrial stromal cells through multiple mechanisms, including
      its regulation of Igfbp3 and Mmp3 transcription.

PMID- 22639810
TI  - Asymmetric female preferences for courtship pheromones in two closely-related
      newt species, the smooth newt (Lissotriton vulgaris) and the Carpathian newt (L.
      montandoni) (Salamandridae).
AB  - The smooth (Lissotriton vulgaris) and Carpathian (L. montandoni) newts are sister
      species. These are separated by a moderate genetic distance, but exhibit striking
      morphological differences, especially in male epigamic traits. In the areas where
      they co-occur, they readily mate with each other and produce viable hybrids.
      However, a high level of pre-zygotic isolation with an unknown behavioral basis
      has been reported. The complex courtship of newts consists of at least three
      types of modality: chemical, visual, and tactile. The relative significance of
      these in mate choice is unclear, but it is commonly accepted that pheromones are
      an important communication channel. The goal of this study was to determine
      whether the females of L. vulgaris and L. montandoni exhibit preferences for
      conspecific extracts from the pheromone-producing abdominal (dorsal) glands.
      Females of both species spent more time in proximity to the source of the
      abdominal gland extracts of their own species when a liver extract was presented
      as an alternative. In a second trial, females were simultaneously confronted with
      conspecific and heterospecific abdominal gland extracts. Asymmetric preferences
      were found. Lissotriton vulgaris females were not selective, whereas L.
      montandoni females preferred the conspecific abdominal gland extract. This
      finding is consistent with the results of earlier experiments on mate choice in
      these species. The results strongly indicate that pheromones play a crucial role
      in courtship and species recognition in this pair of closely related, hybridizing
      species.

PMID- 22639809
TI  - Genetic variation and differentiation of Gekko gecko from different populations
      based on mitochondrial cytochrome b gene sequences and karyotypes.
AB  - Black-spotted and red-spotted tokay geckos are distributed in different regions
      and have significant differences in morphological appearance, but have been
      regarded as the same species, Gekko gecko, in taxonomy. To determine whether
      black-spotted and red-spotted tokay geckos are genetically differentiated, we
      sequenced the entire mitochondrial cytochrome b gene (1147 bp) from 110
      individuals of Gekko gecko collected in 11 areas including Guangxi China, Yunnan
      China, Vietnam, and Laos. In addition, we performed karyotypic analyses of black
      spotted tokay geckos from Guangxi China and red-spotted tokay geckos from Laos.
      These phylogenetic analyses showed that black-spotted and red-spotted tokay
      geckos are divided into two branches in molecular phylogenetic trees. The average
      genetic distances are as follows: 0.12-0.47% among six haplotypes in the black
      spotted tokay gecko group, 0.12-1.66% among five haplotypes in the red-spotted
      tokay gecko group, and 8.76-9.18% between the black-spotted and red-spotted tokay
      geckos, respectively. The karyotypic analyses showed that the karyotype formula
      is 2n = 38 = 8m + 2sm + 2st + 26t in red-spotted tokay geckos from Laos compared
      with 2n = 38 = 8m + 2sm + 28t in black-spotted tokay geckos from Guangxi China.
      The differences in these two kinds of karyotypes were detected on the 15th
      chromosome. The clear differences in genetic levels between black-spotted and red
      spotted tokay geckos suggest a significant level of genetic differentiation
      between the two.

PMID- 22639811
TI  - Morphometric variation in the pusillus group of the genus Rhinolophus (Mammalia:
      Chiroptera: Rhinolophidae) in East Asia.
AB  - Based on 203 specimens belonging to the Rhinolophus "pusillus group" (Mammalia:
      Chiroptera: Rhinolophidae), univariate and multivariate morphometric analyses
      using 19 characters were performed to assess the confused species taxonomy. The
      results indicated that R. pusillus (including calidus, parcus, and szechuanus) in
      the continental region and Hainan Island of China and "R. cornutus" in Japan are
      morphologically divergent species. Rhinolophus cornutus should be further split
      into R. cornutus (including orii, pumilus, and miyakonis) in the main islands of
      Japan, the Amami and Okinawa Group of the central Ryukyu Archipelago, and Miyako
      Group of the southern Ryukyus; and R. perditus and R. imaizumii from the Yaeyama
      Group in the southern Ryukyus. Rhinolophus monoceros from Taiwan is
      morphologically more similar to species in Japan than to R. pusillus. In addition
      to R. pusillus, another form that is morphologically similar to species in Japan
      was recognized from Langzhong in Sichuan Province; this may represent an
      undescribed species, and further examination is necessary to determine its
      taxonomic status. Specimens from Guang'an in Sichuan Province, China, are also
      different from the others, and are characterized by the smallest skull size.
      Although further studies are required, these specimens were tentatively
      identified as R. subbadius.

PMID- 22639812
TI  - Description of three Pristionchus species (Nematoda: Diplogastridae) from Japan
      that form a cryptic species complex with the model organism P. pacificus.
AB  - Three new species of Pristionchus (P. exspectatus, P. arcanus, and P. japonicus)
      are described from Japan. They are morphologically similar, with P. exspectatus
      and P. arcanus being almost indistinguishable from the model organism P.
      pacificus. Reproductive isolation, namely the inability to produce interfertile
      F1 hybrids, separates all species pairs in the species complex. Additionally, all
      three new species are distinguished from P. pacificus  Sommer, Carta, Kim, and
      Sternberg, 1996  by having a gonochoristic instead of hermaphroditic mode of
      reproduction. In addition to its reproductive isolation, P. japonicus is distinct
      from other Pristionchus species by its arrangement of genital papillae. All
      species in the complex are separated from each other by molecular sequence
      divergence, as indicated by analysis of 27 nuclear protein-coding genes and
      unique sequences of the small subunit ribosomal RNA gene. The identification of a
      species complex that includes P. pacificus is invaluable for studies of
      population genetics, speciation, and macroevolution, particularly the evolution
      of hermaphroditism in the genus.

PMID- 22639816
TI  - An Invitation to Create Books and Monographs on Frontier Developments in
      Biological Structure, Dynamics, Interactions & Expression.

PMID- 22639818
TI  - Not all obstructive cardiac lesions are created equal: double-chamber right
      ventricle in pregnancy.
AB  - Double-chambered right ventricle (DCRV) is a rare form of right ventricular
      outflow tract (RVOT) obstruction accounting for approximately 1% of patients with
      congenital heart disease. It consists of an anomalous muscle bundle that divides
      the right ventricle usually between the sinus (inlet) and the infundibulum
      (outlet). This division creates a proximal chamber with high pressure and a
      distal chamber with low pressure. The hemodynamic obstruction of the RVOT is
      usually an acquired phenomenon, however the substrate for the anomalous muscle
      bundle is likely congenital. The diagnosis of DCRV should be considered in the
      young patient with an elevated right ventricular systolic pressure and
      intracavitary gradient. Echocardiography and cardiac MRI are the principal
      diagnostic tools for the assessment of DCRV. This entity is often misdiagnosed as
      pulmonary hypertension in the young patient, and can often go overlooked and
      untreated for many years. Definitive therapy involves surgical resection of the
      muscle bundle. This can often be curative and if done in a timely fashion, may
      prevent right ventricular remodeling. We describe the unique diagnostic dilemma,
      the course and management of a young adult with DCRV during pregnancy.

PMID- 22639817
TI  - Clinical significance of erythropoietin receptor expression in oral squamous cell
      carcinoma.
AB  - BACKGROUND: Hypoxic tumors are refractory to radiation and chemotherapy. High
      expression of biomarkers related to hypoxia in head and neck cancer is associated
      with a poorer prognosis. The present study aimed to evaluate the
      clinicopathological significance of erythropoietin receptor (EPOR) expression in
      oral squamous cell carcinoma (OSCC). METHODS: The study included 256 patients who
      underwent primary surgical resection between October 1996 and August 2005 for
      treatment of OSCC without previous radiotherapy and/or chemotherapy.
      Clinicopathological information including gender, age, T classification, N
      classification, and TNM stage was obtained from clinical records and pathology
      reports. The mRNA and protein expression levels of EPOR in OSCC specimens were
      evaluated by Q-RT-PCR, Western blotting and immunohistochemistry assays. RESULTS:
      We found that EPOR were overexpressed in OSCC tissues. The study included 17
      women and 239 men with an average age of 50.9 years (range, 26-87 years). The
      mean follow-up period was 67 months (range, 2-171 months). High EPOR expression
      was significantly correlated with advanced T classification (p < 0.001), advanced
      TNM stage (p < 0.001), and positive N classification (p = 0.001). Furthermore,
      the univariate analysis revealed that patients with high tumor EPOR expression
      had a lower 5-year overall survival rate (p = 0.0011) and 5-year disease-specific
      survival rate (p = 0.0017) than patients who had low tumor levels of EPOR.
      However, the multivariate analysis using Cox's regression model revealed that
      only the T and N classifications were independent prognostic factors for the 5
      year overall survival and 5-year disease-specific survival rates. CONCLUSIONS:
      High EPOR expression in OSCC is associated with an aggressive tumor behavior and
      poorer prognosis in the univariate analysis among patients with OSCC. Thus, EPOR
      expression may serve as a treatment target for OSCC in the future.

PMID- 22639819
TI  - Optimized molecular structure of photoreactive biocompatible block copolymers for
      surface modification of metal substrates.
AB  - Poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(2-methacryloyloxyethyl
      phosphate-co-2-cinnamoyloxyethyl methacrylate) (PMPC-b-P(MPA/CMA)) was prepared
      by reversible addition-fragmentation chain transfer (RAFT)-controlled radical
      polymerization. The block copolymers were coated on stainless steel (SUS316L) and
      other metal substrates, and then the surface was subsequently irradiated with UV
      light. The wettability of a specimen surface treated with a block copolymer was
      improved in comparison with that of an untreated SUS316L plate. From X-ray
      photoelectron spectroscopy (XPS) data, it was clear that the P(MPA/CMA) block
      worked as a binding site on the SUS316L surface. The surface density of the block
      copolymer-immobilized SUS316L surface was influenced by the molecular weight of
      the PMPC block. The stability of the immobilized layer was improved by UV
      irradiation, which induced intermolecular dimerization of the CMA. In addition to
      the SUS316L surface, various other metal surfaces could be modified by surface
      immobilization of block copolymers. Serum protein adsorption and fibroblast
      adhesion were effectively reduced by surface immobilization of block copolymers
      with optimal molecular weight of PMPC block. The nonfouling property was
      preserved after 1 week of cell cultivation. 

PMID- 22639820
TI  - Global patterns in the impact of marine herbivores on benthic primary producers.
AB  - Despite the importance of consumers in structuring communities, and the
      widespread assumption that consumption is strongest at low latitudes, empirical
      tests for global scale patterns in the magnitude of consumer impacts are limited.
      In marine systems, the long tradition of experimentally excluding herbivores in
      their natural environments allows consumer impacts to be quantified on global
      scales using consistent methodology. We present a quantitative synthesis of 613
      marine herbivore exclusion experiments to test the influence of consumer traits,
      producer traits and the environment on the strength of herbivore impacts on
      benthic producers. Across the globe, marine herbivores profoundly reduced
      producer abundance (by 68% on average), with strongest effects in rocky
      intertidal habitats and the weakest effects on habitats dominated by vascular
      plants. Unexpectedly, we found little or no influence of latitude or mean annual
      water temperature. Instead, herbivore impacts differed most consistently among
      producer taxonomic and morphological groups. Our results show that grazing
      impacts on plant abundance are better predicted by producer traits than by large
      scale variation in habitat or mean temperature, and that there is a previously
      unrecognised degree of phylogenetic conservatism in producer susceptibility to
      consumption.

PMID- 22639821
TI  - Angiotensin-(1-7) in kidney disease: a review of the controversies.
AB  - Ang-(1-7) [angiotensin-(1-7)] is a biologically active heptapeptide component of
      the RAS (renin-angiotensin system), and is generated in the kidney at relatively
      high levels, via enzymatic pathways that include ACE2 (angiotensin-converting
      enzyme 2). The biological effects of Ang-(1-7) in the kidney are primarily
      mediated by interaction with the G-protein-coupled receptor Mas. However, other
      complex effects have been described that may involve receptor-receptor
      interactions with AT(1) (angiotensin II type 1) or AT(2) (angiotensin II type 2)
      receptors, as well as nuclear receptor binding. In the renal vasculature, Ang-(1
      7) has vasodilatory properties and it opposes growth-stimulatory signalling in
      tubular epithelial cells. In several kidney diseases, including hypertensive and
      diabetic nephropathy, glomerulonephritis, tubulointerstitial fibrosis, pre
      eclampsia and acute kidney injury, a growing body of evidence supports a role for
      endogenous or exogenous Ang-(1-7) as an antagonist of signalling mediated by
      AT(1) receptors and thereby as a protector against nephron injury. In certain
      experimental conditions, Ang-(1-7) appears to paradoxically exacerbate renal
      injury, suggesting that dose or route of administration, state of activation of
      the local RAS, cell-specific signalling or non-Mas receptor-mediated pathways may
      contribute to the deleterious responses. Although Ang-(1-7) has promise as a
      potential therapeutic agent in humans with kidney disease, further studies are
      required to delineate its signalling mechanisms in the kidney under physiological
      and pathophysiological conditions.

PMID- 22639822
TI  - Combustion-derived nanoparticle exposure and household solid fuel use in Xuanwei
      and Fuyuan, China.
AB  - Combustion-derived nanoparticles (CDNPs) have not been readably measurable until
      recently. We conducted a pilot study to determine CDNP levels during solid fuel
      burning. The aggregate surface area of CDNP (MUm(2)/cm(3)) was monitored
      continuously in 15 Chinese homes using varying fuel types (i.e. bituminous coal,
      anthracite coal, wood) and stove types (i.e. portable stoves, stoves with
      chimneys, firepits). Information on fuel burning activities was collected and
      PM(2.5) levels were measured. Substantial exposure differences were observed
      during solid fuel burning (mean: 228.1 MUm(2)/cm(3)) compared to times without
      combustion (mean: 14.0 MUm(2)/cm(3)). The observed levels during burning were
      reduced by about four-fold in homes with a chimney (mean: 92.1 MUm(2)/cm(3); n =
      9), and effects were present for all fuel types. Each home's CDNP measurement was
      only moderately correlated with the respective PM(2.5) measurements (r (2) =
      0.43; p = 0.11). Our results indicate that household coal and wood burning
      contributes to indoor nanoparticle levels, which are not fully reflected in
      PM(2.5) measurements.

PMID- 22639823
TI  - Dentofacial effects of two facemask therapies for maxillary protraction.
AB  - OBJECTIVE: To compare the dentofacial effects of maxillary protraction with two
      facemask therapies in growing Class III patients: facemask in association with
      miniscrew implants (MSI/FM) and facemask with rapid maxillary expanders (RME/FM).
      MATERIALS AND METHODS: Forty-three Chinese patients with Class III malocclusion
      and maxillary deficiency were randomly assigned to a MSI/FM sample of 20 patients
      and a RME/FM sample of 23 subjects. The changes in dentofacial cephalometric
      variables from the beginning (T1) to the end of treatment (T2) were compared with
      t-test for paired samples in both groups and for independent samples between the
      two groups. RESULTS: No significant cephalometric differences were observed
      between the two groups in active treatment effects except for maxillary dental
      variables. However, significant favorable changes in both maxillary and
      mandibular skeletal components were noted in two groups after treatment. Sagittal
      measurements showed the maxilla was advanced, mandibular projection was reduced,
      and the relative sagittal intermaxillary discrepancy improved. Patients
      experienced additional unfavorable outcomes of clockwise rotation of the mandible
      as well as retroclination of the lower incisors. The soft tissue profile was
      improved remarkably in both groups. Proclination of the maxillary incisors and
      mesialization of the maxillary dentition were significantly different between the
      two groups. The increases in U1-SN, U1-VR, and U6-VR were 6.41 degrees , 2.78 mm,
      and 1.24 mm less in the MSI/FM group than in the RME/FM group, respectively.
      CONCLUSIONS: Compared with the RME/FM therapy, the MSI/FM protocol using a
      smaller magnitude of protraction force improves skeletal relationships and soft
      tissue profile and reduces the undesired dentoalveolar effects.

PMID- 22639824
TI  - Dental anomalies and clinical features in patients with maxillary canine
      impaction.
AB  - OBJECTIVE: To analyze the prevalence, distribution, clinical features, and
      relationship with dental anomalies of maxillary canine impaction. MATERIALS AND
      METHODS: The complete pretreatment records of 1674 orthodontic patients were
      examined. Subjects with maxillary impacted canines were divided into two study
      groups: a palatally displaced canine (PDC) group (114 patients) and a buccally
      displaced canine (BDC) group (37 patients). These were compared to a control
      group of 151 patients who were randomly selected from the initial sample without
      maxillary canine impaction. The significance of associations between canine
      impaction and dental and clinical features and anomalies was examined with the
      chi-square test. RESULTS: PDC patients presented with normal overjet and facial
      profile and a lower degree of dental arch crowding in comparison to the control
      patients. PDC patients showed a higher prevalence of impaction of other teeth,
      dental aplasia, transposition, and peg-shaped maxillary lateral incisors (odds
      ratios 3.3, 2.6, 8.3, and 5.8, respectively). CONCLUSION: PDC was frequently the
      only orthodontic problem of patients. BDC group patients did not present with
      notable differences in clinical and dental features or dental anomalies compared
      to control subjects.

PMID- 22639828
TI  - Absence of BRAF V600E mutation in hematologic malignancies excluding hairy-cell
      leukemia.

PMID- 22639829
TI  - Potato consumption and cardiovascular disease risk factors among Iranian
      population.
AB  - BACKGROUND: Previous studies investigated the effects of dietary glycaemic index
      and glycaemic load on cardiovascular risk factors. Little evidence is available
      regarding the association between potato intake and cardiovascular risk factors
      in Iran. OBJECTIVE: This cross-sectional study was conducted in the first stage
      of Isfahan Healthy Heart Programme. METHODS: A total of 4774 subjects were
      included in the present study. Dietary intake was assessed with a 49-item food
      frequency questionnaire. Biochemical assessments were done according to the
      standard protocol. RESULTS: There were significant associations between potato
      consumption and diabetes mellitus (odds ratio (OR): 1.38; 95% CI: 1.14-1.67; p <
      0.001), high fasting blood sugar level (OR: 1.40; 95% CI: 1.17-1.68; p < 0.001)
      and low serum high density lipoprotein level (OR: 1.10; 95% CI: 1.01-1.20; p =
      0.02) remained after adjustments for possible confounding factors. CONCLUSION: We
      found a positive relation between potato consumption, high fasting blood glucose
      level and diabetes mellitus.

PMID- 22639830
TI  - Vertically aligned BCN nanotubes with high capacitance.
AB  - Using a chemical vapor deposition method, we have synthesized vertically aligned
      BCN nanotubes (VA-BCNs) on a Ni-Fe-coated SiO(2)/Si substrate from a melamine
      diborate precursor. The effects of pyrolysis conditions on the morphology and
      thermal property of grown nanotubes, as well as the nanostructure and composition
      of an individual BCN nanotube, were systematically studied. It was found that
      nitrogen atoms are bonded to carbons in both graphitic and pyridinic forms and
      that the resultant VA-BCNs grown at 1000  degrees C show the highest specific
      capacitance (321.0 F/g) with an excellent rate capability and high durability
      with respect to nonaligned BCN (167.3 F/g) and undoped multiwalled carbon
      nanotubes (117.3 F/g) due to synergetic effects arising from the combined co
      doping of B and N in CNTs and the well-aligned nanotube structure.

PMID- 22639831
TI  - Change of carbon source causes dramatic effects in the phospho-proteome of the
      archaeon Sulfolobus solfataricus.
AB  - Protein phosphorylation is known to occur in Archaea. However, knowledge of
      phosphorylation in the third domain of life is rather scarce. Homology-based
      searches of archaeal genome sequences reveals the absence of two-component
      systems in crenarchaeal genomes but the presence of eukaryotic-like protein
      kinases and protein phosphatases. Here, the influence of the offered carbon
      source (glucose versus tryptone) on the phospho-proteome of Sulfolobus
      solfataricus P2 was studied by precursor acquisition independent from ion count
      (PAcIFIC). In comparison to previous phospho-proteome studies, a high number of
      phosphorylation sites (1318) located on 690 phospho-peptides from 540 unique
      phospho-proteins were detected, thus increasing the number of currently known
      archaeal phospho-proteins from 80 to 621. Furthermore, a 25.8/20.6/53.6
      Ser/Thr/Tyr percentage ratio with an unexpectedly high predominance of tyrosine
      phosphorylation was detected. Phospho-proteins in most functional classes (21 out
      of 26 arCOGs) were identified, suggesting an important regulatory role in S.
      solfataricus. Focusing on the central carbohydrate metabolism in response to the
      offered carbon source, significant changes were observed. The observed complex
      phosphorylation pattern hints at an important physiological function of protein
      phosphorylation in control of the central carbohydrate metabolism, which might
      particularly operate in channeling carbon flux into the respective metabolic
      pathways.

PMID- 22639832
TI  - A 5-year prospective population-based study of juvenile chronic arthritis: onset,
      disease process, and outcome.
AB  - OBJECTIVES: To investigate, in a population-based cohort of patients with
      juvenile chronic arthritis (JCA), onset characteristics, progression, outcome,
      and prognostic factors longitudinally for 5 years. METHODS: This cohort consisted
      of 132 incidence cases identified between 1984 and 1986 in southwestern Sweden
      followed for 5 years with annual reports of subgroup, joint assessment, disease
      activity, eye examinations, laboratory measurements, and medication. At the 5
      year follow-up, the Childhood Health Assessment Questionnaire (Child-HAQ) was
      evaluated. European League Against Rheumatism (EULAR) criteria for diagnosis and
      disease activity were used. RESULTS: During the 5 years only four patients were
      lost to follow-up, 34% changed subgroup and 8% developed uveitis. At the 5-year
      follow-up the disease was active in 12% of the patients, stable in 28%, inactive
      in 25%, and in remission in 34%. Among those examined, 24% had radiological
      changes, of whom half had advanced changes. The Child-HAQ median score at the 5
      year follow-up was 0.13 (range 0.0-1.9). The number of involved joints at
      inclusion correlated positively with active disease at the 5-year follow-up. Age
      at disease onset, the number of involved joints, and the number of joints with
      arthritis correlated positively with continuous disease and Child-HAQ score.
      CONCLUSION. Our study shows a diverse disease course during the first 5 years of
      JCA where one-third changed subgroup and two-thirds did not reach remission. Age
      of disease onset, the number of involved joints, and the number of joints with
      arthritis at inclusion were associated with poor outcome at the 5-year follow-up.

PMID- 22639834
TI  - The treatment of infertility in polycystic ovary syndrome: a brief update.
AB  - Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory
      infertility. Lifestyle change alone is considered the first-line treatment for
      the management of infertile anovulatory PCOS women who are overweight or obese.
      First-line medical ovulation induction therapy to improve fertility outcomes is
      clomiphene citrate, whilst gonadotrophins, laparoscopic ovarian surgery or
      possibly metformin are second line in clomiphene citrate-resistant PCOS women.
      There is currently insufficient evidence to recommend aromatase inhibitors over
      that of clomiphene citrate in infertile anovulatory PCOS women in general or
      specifically in therapy naive or clomiphene citrate-resistant PCOS women.
      IVF/ICSI treatment is recommended either as a third-line treatment or in the
      presence of other infertility factors.

PMID- 22639833
TI  - Haemophilia care in Europe: the ESCHQoL study.
AB  - The aim of this study was to determine the clinical conditions of patients with
      haemophilia within Europe as recommended by the European Commission. In this
      multicentre, cross-sectional, ambispective study, conducted within 21 European
      countries patients' clinical data were collected, amongst others haemophilia
      type, severity, treatment pattern, use of factor products, bleeding, orthopaedic
      joint scores and infections. A total of 1400 patients, 84.3% with haemophilia A
      and 15.7% with haemophilia B were enrolled by 42 centres between 2004 and 2006.
      Thereof, 417 were children (30.0%) and 983 were adults (70.0%). About 70% of
      patients had severe factor deficiency (<1%). More than half of the adults were
      carriers of chronic infections (12.6% HIV, 55.8% HCV), compared to only 3.8%
      children (no HIV, 2.9% HCV). Patients were grouped according to per capita amount
      of clotting factor used in patients' region of residence in 2005: region 1: >5
      IU; region 2: 2-5 IU; region 3: <2 IU. Paediatric and adult patients in region 3
      had median numbers of three and eight joint bleeds, respectively, with worse
      joint scores compared to region 1 with zero and one bleed. Prophylactic therapy
      was used in only 31.3% children and 8.9% adults with severe haemophilia in region
      3 compared to 93.7% and 54.1%, respectively, in region 1. Statistical analysis
      revealed that residence in areas with low factor consumption/availability is the
      most prominent risk factor for joint disease. Access of European patients with
      haemophilia to optimal care with safe factor VIII concentrates is limited and
      depends on the region of residence.

PMID- 22639835
TI  - Selection on non-social traits limits the invasion of social cheats.
AB  - While the conditions that favour the maintenance of cooperation have been
      extensively investigated, the significance of non-social selection pressures on
      social behaviours has received little attention. In the absence of non-social
      selection pressures, patches of cooperators are vulnerable to invasion by cheats.
      However, we show both theoretically, and experimentally with the bacterium
      Pseudomonas fluorescens, that cheats may be unable to invade patches of
      cooperators under strong non-social selection (both a novel abiotic environment
      and to a lesser extent, the presence of a virulent parasite). This is because
      beneficial mutations are most likely to arise in the numerically dominant
      cooperator population. Given the ubiquity of novel selection pressures on
      microbes, these results may help to explain why cooperation is the norm in
      natural populations of microbes.

PMID- 22639836
TI  - Adolescent girl with Down syndrome and lumbar cutaneous melanoma.
AB  - Melanoma has rarely been reported in people with Down syndrome, and its frequency
      in this condition has not been clearly established. We report a 19-year-old woman
      with Down syndrome and lumbar melanoma. This possible association must be kept in
      mind. 

PMID- 22639837
TI  - Left ventricular dyssynchrony and its effects on cardiac function in patients
      with newly diagnosed hypertension.
AB  - OBJECTIVES: Left ventricular (LV) systolic synchrony, defined as simultaneous
      peak contractions of corresponding cardiac segments, is well documented to be
      impaired in hypertension but its effect on LV function is not clear. The aim of
      this study was to assess the impacts of LV systolic dyssynchrony on LV function
      in newly diagnosed hypertensives. METHODS: Forty-eight newly diagnosed
      hypertensive patients and 33 controls were enrolled. All study population
      underwent a comprehensive echocardiographic evaluation including tissue synchrony
      imaging. The time to regional peak systolic tissue velocity (Ts) in LV by 12
      segmental models was measured and two parameters of systolic dyssynchrony were
      computed. RESULTS: Baseline demographic characteristics were similar in both
      study groups. Dyssynchrony parameters prolonged in newly diagnosed hypertensive
      patients compared to controls: the standard deviation (SD) of 12 LV segments Ts
      (40.2 +/- 21 vs. 26.2 +/- 13.4, P = 0.003); the maximal difference in Ts between
      any 2 of 12 LV segments (123.3 +/- 61.5 vs. 79.8 +/- 37.9, P = 0.001). In
      multivariable analysis, Ts-SD-12 was found to be an independent predictor for
      systolic function (beta=-0.29, P = 0.008). But, both diastolic and global
      functions were not independently related to Ts-SD-12. CONCLUSION: LV
      synchronization is impaired in newly diagnosed hypertensive patients. LV
      dyssynchrony is one of the independent predictors of systolic function in
      hypertensive patients.

PMID- 22639838
TI  - Inter-rater reliability of the evaluation of muscular chains associated with
      posture alterations in scoliosis.
AB  - BACKGROUND: In the Global postural re-education (GPR) evaluation, posture
      alterations are associated with anterior or posterior muscular chain impairments.
      Our goal was to assess the reliability of the GPR muscular chain evaluation.
      METHODS:  DESIGN: Inter-rater reliability study. Fifty physical therapists (PTs)
      and two experts trained in GPR assessed the standing posture from photographs of
      five youths with idiopathic scoliosis using a posture analysis grid with 23
      posture indices (PI). The PTs and experts indicated the muscular chain associated
      with posture alterations. The PTs were also divided into three groups according
      to their experience in GPR. Experts' results (after consensus) were used to
      verify agreement between PTs and experts for muscular chain and posture
      assessments. We used Kappa coefficients (K) and the percentage of agreement (%A)
      to assess inter-rater reliability and intra-class coefficients (ICC) for
      determining agreement between PTs and experts. RESULTS: For the muscular chain
      evaluation, reliability was moderate to substantial for 12 PI for the PTs (%A: 56
      to 82; K: 0.42 to 0.76) and perfect for 19 PI for the experts. For posture
      assessment, reliability was moderate to substantial for 12 PI for the PTs (%A >
      60%; K: 0.42 to 0.75) and moderate to perfect for 18 PI for the experts (%A: 80
      to 100; K: 0.55 to 1.00). The agreement between PTs and experts was good for most
      muscular chain evaluations (18 PI; ICC: 0.82 to 0.99) and PI (19 PI; ICC: 0.78 to
      1.00). CONCLUSIONS: The GPR muscular chain evaluation has good reliability for
      most posture indices. GPR evaluation should help guide physical therapists in
      targeting affected muscles for treatment of abnormal posture patterns.

PMID- 22639839
TI  - Helicobacter pylori biofilm: a protective environment for bacterial
      recombination.
AB  - AIMS: The aim of this work was to investigate the interaction between two
      Helicobacter pylori strains in promoting genetic transfer, when grown in the
      biofilm mode. METHODS AND RESULTS: Biofilms produced by H. pylori 9/10 (A), H.
      pylori 15/4 (B) and their mixture (C) were studied for biomass production and
      cell viability. The genetic heterogeneity of 45 clones, coming from mature
      biofilm of co-cultured H. pylori strains was studied by both RAPD and cagA (EPIYA
      motifs)/vacA virulence genes analysis. Helicobacter pylori A, B and C developed a
      well-structured biofilm without significant differences in viability. No
      significant differences were recorded between A and B biomass measurement,
      whereas C biofilm expressed a significant (P < 0.001) higher adhesive capability
      when compared with A and B biofilms. C-clones DNA-fingerprintings showed an high
      genetic heterogeneity (mean similarity value = 0.528). The 60% of C-clones
      displayed vacA allelic combination s1i1m1m2 associated with cagA EPIYA motif
      pattern P1P2P3P3P3. CONCLUSIONS: Biofilms developed by multiple H. pylori strains
      are more complex than those associated with single strains. Such condition might
      promote the genetic exchange favouring the generation of more virulent strains.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The 'biofilm niche' represents a successful
      strategy and a suitable environment for promoting bacterial population
      persistence by recombination events.

PMID- 22639840
TI  - HIV and hepatitis C virus coinfection in Canada: challenges and opportunities for
      reducing preventable morbidity and mortality.
AB  - OBJECTIVES: Hepatitis C virus (HCV) has emerged as an important health problem in
      the era of effective HIV treatment. However, very few data exist on the health
      status and disease burden of HIV/HCV-coinfected Canadians. METHODS: HIV/HCV
      coinfected patients were enrolled prospectively in a multicentre cohort from 16
      centres across Canada between 2003 and 2010 and followed every 6 months. We
      determined rates of a first liver fibrosis or endstage liver disease (ESLD) event
      and all-cause mortality since cohort enrolment and calculated standardized
      mortality ratios compared with the general Canadian population. RESULTS: A total
      of 955 participants were enrolled in the study and followed for a median of 1.4
      (interquartile range 0.5-2.3) years. Most were male (73%) with a median age of
      44.5 years; 13% self-identified as aboriginal. There were high levels of current
      injecting drug and alcohol use and poverty. Observed event rates [per 100 person
      years; 95% confidence interval (CI)] were: significant fibrosis (10.21; 8.49,
      12.19), ESLD (3.16; 2.32, 4.20) and death (3.72; 2.86, 4.77). The overall
      standardized mortality ratio was 17.08 (95% CI 12.83, 21.34); 12.80 (95% CI 9.10,
      16.50) for male patients and 28.74 (95% CI 14.66, 42.83) for female patients. The
      primary causes of death were ESLD (29%) and overdose (24%). CONCLUSIONS: We
      observed excessive morbidity and mortality in this HIV/HCV-coinfected population
      in care. Over 50% of observed deaths may have been preventable. Interventions
      aimed at improving social circumstances, reducing harm from drug and alcohol use
      and increasing the delivery of HCV treatment in particular will be necessary to
      reduce adverse health outcomes among HIV/HCV-coinfected persons.

PMID- 22639841
TI  - Methyl jasmonate responsive proteins in Brassica napus guard cells revealed by
      iTRAQ-based quantitative proteomics.
AB  - Stomata on leaf epidermis formed by pairs of guard cells control CO(2) intake and
      water transpiration, and respond to different environmental conditions. Stress
      induced stomatal closure is mediated via an intricate hormone network in guard
      cells. Although methyl jasmonate (MeJA) has been intensively studied for its
      function in plant defense, the molecular mechanisms underlying its function in
      stomatal movement are not fully understood. Here we report the effects of MeJA on
      Brassica napus stomatal movement and H(2)O(2) production. Using the isobaric tags
      for relative and absolute quantitation (iTRAQ) approach, we have identified 84
      MeJA-responsive proteins in B. napus guard cells. Most of the genes encoding
      these proteins contain jasmonate-responsive elements in the promoters, indicating
      that they are potentially regulated at the transcriptional level. Among the
      identified proteins, five protein changes after MeJA treatment were validated
      using Western blot analysis. The identification of the MeJA-responsive proteins
      has revealed interesting molecular mechanisms underlying MeJA function in guard
      cells, which include homeostasis of H(2)O(2) production and scavenging, signaling
      through calcium oscillation and protein (de)phosphorylation, gene transcription,
      protein modification, energy balance, osmoregulation, and cell shape modulation.
      The knowledge of the MeJA-responsive proteins has improved our understanding of
      MeJA signaling in stomatal movement, and it may be applied to crop engineering
      for enhanced yield and stress tolerance.

PMID- 22639843
TI  - Long-term survival in patients with clear cell adenocarcinoma of ovary treated
      with irinotecan hydrochloride plus cisplatin therapy as first-line chemotherapy.
AB  - AIM: Several previous reports showed that irinotecan hydrochloride plus cisplatin
      (CPT-P) was a candidate first-line chemotherapy regimen for clear cell
      adenocarcinoma of the ovary (CCC). However, long-term survival in CCC patients
      treated with CPT-P as first-line chemotherapy remains to be determined. The aim
      of the present study was to evaluate the long-term results of CPT-P as first-line
      chemotherapy for CCC. MATERIAL AND METHODS: We performed a retrospective review
      of 31 patients with CCC who were treated with CPT-P between 1996 and 2004.
      RESULTS: The median follow-up period was 91 months. The estimated 8-year overall
      survival (OS) rate in all patients was 64.5%, while the rate in 18 stage I, 21
      stage I/II, and 10 stage III/IV patients was 88.9%, 85.7%, and 20.0%,
      respectively. The estimated 8-year OS rate in patients with pT1/pT2 disease was
      87.0%, while the 3-year OS rate in patients with pT3 disease was 0%. Univariate
      analysis using the log-rank test revealed that Eastern Cooperative Oncology Group
      performance-status 1, pT3 stage, and presence of residual disease (stage II-IV)
      were significantly correlated with shortened patient survival. Multiple
      regression analysis revealed that pT3 predicted worse OS in patients with CCC
      than pT1 (P<0.001) or pT2 disease (P < 0.005). CONCLUSION: The long-term results
      suggest CPT-P as a candidate in first-line chemotherapy for CCC in not only stage
      I, but also in optimally debulked stage II-IV patients with pT1/pT2 disease.

PMID- 22639842
TI  - Common genetic polymorphisms of microRNA biogenesis pathway genes and breast
      cancer survival.
AB  - BACKGROUND: Although the role of microRNA's (miRNA's) biogenesis pathway genes in
      cancer development and progression has been well established, the association
      between genetic variants of this pathway genes and breast cancer survival is
      still unknown. METHODS: We used genotype data available from a previously
      conducted case-control study to investigate association between common genetic
      variations in miRNA biogenesis pathway genes and breast cancer survival. We
      investigated the possible associations between 41 germ-line single-nucleotide
      polymorphisms (SNPs) and both disease free survival (DFS) and overall survival
      (OS) among 488 breast cancer patients. During the median follow-up of 6.24 years,
      90 cases developed disease progression and 48 cases died. RESULTS: Seven SNPs
      were significantly associated with breast cancer survival. Two SNPs in AGO2
      (rs11786030 and rs2292779) and DICER1 rs1057035 were associated with both DFS and
      OS. Two SNPs in HIWI (rs4759659 and rs11060845) and DGCR8 rs9606250 were
      associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated
      with only OS. The most significant association was observed in variant allele of
      AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95%
      confidence interval (CI), 1.41-4.88) and in minor allele homozygote of AGO2
      rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69). We also
      found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying
      0 to 2 high-risk genotypes, those carrying 3 or 4-6 high-risk genotypes had an
      increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18-
      3.93) and 4.47 (95% CI, 2.45- 8.14), respectively (P for trend, 6.11E-07).
      CONCLUSIONS: Our results suggest that genetic variants in miRNA biogenesis
      pathway genes may be associated with breast cancer survival. Further studies in
      larger sample size and functional characterizations are warranted to validate
      these results.

PMID- 22639844
TI  - Migratory pathways of GABAergic interneurons when they enter the neocortex.
AB  - Inhibitory gamma-aminobutyric-acid-containing interneurons play important roles
      in the functions of the neocortex. During rodent development, most neocortical
      interneurons are generated in the subpallium and migrate tangentially toward the
      neocortex. They migrate through multiple pathways to enter the neocortex. Failure
      of interneuron migration through these pathways during development leads to an
      abnormal distribution and abnormal functions of interneurons in the postnatal
      brain. Because of recent discoveries regarding the novel origins and migratory
      pathways of neocortical interneurons, in this article we review the literature on
      the migratory pathways of interneurons when they enter the neocortex.

PMID- 22639845
TI  - Coronally advanced flap with and without connective tissue graft for the
      treatment of single maxillary gingival recession with loss of inter-dental
      attachment. A randomized controlled clinical trial.
AB  - BACKGROUND: The aim of this randomized clinical trial (RCT) was to evaluate the
      adjunctive benefit of Connective Tissue Graft (CTG) to Coronally Advanced Flap
      (CAF) for the treatment of gingival recession associated with inter-dental
      clinical attachment loss equal or smaller to the buccal attachment loss (RT2).
      MATERIAL AND METHODS: A total of 29 patients with one recession were enrolled; 15
      patients were randomly assigned to CAF+CTG while 14 to CAF alone. Measurements
      were performed by a blind and calibrated examiner. Outcome measures included
      complete root coverage (CRC), recession reduction (RecRed), Root coverage
      Esthetic Score (RES), intra-operative and post-operative morbidity, and root
      sensitivity. RESULTS: After 6 months, CAF+CTG resulted in better outcomes in
      terms of CRC (adjusted OR = 15.51, p = 0.0325) than CAF alone. CRC was observed
      in >80% of the cases treated with CAF+CTG when the baseline amount of inter
      dental CAL was <= 3 mm. No difference was detected in term of RecRed. CAF+CTG was
      associated with longer surgical-time (p < 0.0001), higher number of days with
      post-operative morbidity (p = 0.0222) and the need for a greater number of
      analgesics (p = 0.0178) than CAF alone. No difference for final RES score was
      detected (p = 0.1612). CONCLUSION: Both treatments can provide CRC in single
      gingival recession with inter-dental CAL loss. The application of CTG under CAF
      resulted in predictable CRC when inter-dental CAL was <= 3 mm.

PMID- 22639846
TI  - Recognition of a core fragment ofBeauveria bassiana hydrophobin gene promoter (P
      hyd1) and its special use in improving fungal biocontrol potential.
AB  - To identify a suitable promoter for use in engineering fungal entomopathogens to
      improve heterologous gene expression and fungal biocontrol potential, a 1798 bp
      promoter (P hyd1) upstream of Beauveria bassiana class I hydrophobin gene (hyd1)
      was optimized by upstream truncation and site-directed mutation. A truncated 1290
      bp fragment (P hyd1-t1) drove eGFP expression in B. bassiana much more
      efficiently than full-length P hyd1. Further truncating P hyd1-t1 to 1179, 991
      and 791 bp or mutating one of the binding domains of three transcription factors
      in P hyd1-t1 reduced significantly the expression of eGFP (enhanced green
      fluorescence protein). Under P hyd1-t1 control, eGFP was expressed more
      abundantly in conidiogenic cells and conidia than in mycelia. Therefore, P hyd1
      t1 was used to integrate a bacterium-derived, insect midgut-specific toxin
      (vip3Aa1) gene into B. bassiana, yielding a transgenic strain (BbHV8) expressing
      9.8-fold more toxin molecules in conidia than a counterpart strain (BbV28)
      expressing the toxin under the control of P gpdA, a promoter widely used for gene
      expression in fungi. Consequently, BbHV8 showed much higher per os virulence to
      Spodoptera litura larvae than BbV28 in standardized bioassays with normal conidia
      for both cuticle penetration and ingestion or heat-killed conidia for ingestion
      only. Conclusively, P hyd1-t1 is a useful tool for enhancing beneficial protein
      expression, such as vip3Aa1, in fungal conidia, which are the active ingredients
      of mycoinsecticides.

PMID- 22639847
TI  - Adhesive layer-by-layer films of carboxymethylated cellulose nanofibril-dopamine
      covalent bioconjugates inspired by marine mussel threads.
AB  - The preparation of multifunctional films and coatings from sustainable, low-cost
      raw materials has attracted considerable interest during the past decade. In this
      respect, cellulose-based products possess great promise due not only to the
      availability of large amounts of cellulose in nature but also to the new classes
      of nanosized and well-characterized building blocks of cellulose being prepared
      from trees or annual plants. However, to fully utilize the inherent properties of
      these nanomaterials, facile and also sustainable preparation routes are needed.
      In this work, bioinspired hybrid conjugates of carboxymethylated cellulose
      nanofibrils (CNFC) and dopamine (DOPA) have been prepared and layer-by-layer
      (LbL) films of these modified nanofibrils have been built up in combination with
      a branched polyelectrolyte, polyethyleneimine (PEI), to obtain robust, adhesive,
      and wet-stable nanocoatings on solid surfaces. It is shown that the chemical
      functionalization of CNFCs with DOPA molecules alters their conventional
      properties both in liquid dispersion and at the interface and also influences the
      LbL film formation by reducing the electrostatic interaction. Although the CNFC
      DOPA conjugates show a lower colloidal stability in aqueous dispersions due to
      charge suppression, it was possible to prepare the LbL films through the
      consecutive deposition of the building blocks. Adhesive forces between multilayer
      films prepared using chemically functionalized CNFCs and a silica probe are much
      stronger in the presence of Fe(3+) than those between a multilayer film prepared
      from unmodified nanofibrils and a silica probe. The present work demonstrates a
      facile way to prepare chemically functionalized cellulose nanofibrils whereby
      more extended applications can produce novel cellulose-based materials with
      different functionalities.

PMID- 22639848
TI  - Coping with multimorbidity in old age--a qualitative study.
AB  - BACKGROUND: Comparatively few studies address the problems related to
      multimorbidity. This is surprising, since multimorbidity is a particular
      challenge for both general practitioners and patients. This study focuses on the
      latter, analyzing the way patients aged 65-85 cope with multimorbidity. METHODS:
      19 narrative in-depth interviews with multimorbid patients were conducted. The
      data was analysed using grounded theory. Of the 19 interviewed patients 13 were
      female and 6 male. Mean age was 75 years. Participating patients showed a
      relatively homogeneous socio-economic status. Patients were recruited from the
      German city of Hamburg and the state of North Rhine-Westphalia. RESULTS: Despite
      suffering from multimorbidity, interviewees held positive attitudes towards life:
      At the social level, patients tried to preserve their autonomy to the most
      possible extent. At the emotional level, interviewees oscillated between anxiety
      and strength - having, however, a positive approach to life. At the practical
      level, patients aimed at keeping their diseases under control. The patients
      tended to be critical in regards to medication. CONCLUSIONS: These findings might
      have implications for the treatment of multimorbid patients in primary care and
      further research: The generally presumed passivity of older individuals towards
      medical treatment, which can be found in literature, is not evident among our
      sample of older patients. In future, treatment of these patients might take their
      potential for pro-active cooperation more strongly into account than it is
      currently the case.

PMID- 22639849
TI  - MALDI MS imaging as a powerful tool for investigating synovial tissue.
AB  - OBJECTIVE: To identify and image protein biomarker candidates in the synovial
      tissue of patients with rheumatoid arthritis (RA) and patients with
      osteoarthritis (OA). METHODS: A novel matrix-assisted laser desorption/ionization
      (MALDI) imaging mass spectrometry (IMS) technique was applied to the analysis of
      synovial tissue. Patients were classified according to the American College of
      Rheumatology (ACR) criteria for RA. Frozen sections were stained to obtain
      morphological data. Serial sections were desiccated, and spotted with matrix for
      MALDI analysis. Ions generated by laser irradiation of the tissue were separated
      in time, based on their m/z ratio, and were subsequently detected. IMS was used
      in a 'profiling' mode to detect discrete spots for rapid evaluation of proteomic
      patterns in various tissue compartments. Photomicrographs of the stained tissue
      images were reviewed by a pathologist. Areas of interest (10 discrete
      areas/compartment) were marked digitally and the histology-annotated images were
      merged to form a photomicrograph of the section taken before the MALDI
      measurement. Pixel coordinates of these areas were transferred to a robotic
      spotter, the matrix was spotted, and the coordinates of the spots were
      transferred to a mass spectrometer for spectral acquisition. The data generated
      were then subjected to biocomputation analysis to reveal the biomarker
      candidates. RESULTS: Several peaks (m/z) consistent in mass with calgranulins,
      defensins, and thymosins were detected and their distribution in various synovial
      compartments (synovial lining and sublining layer) was demonstrated. CONCLUSION:
      MALDI IMS is a powerful tool for the rapid detection of numerous proteins (in
      situ proteomics) and was applied here for the analysis of the distribution of
      proteins in synovial tissue sections.

PMID- 22639850
TI  - Quantification of four arsenic species in fruit juices by ion-chromatography
      inductively coupled plasma-mass spectrometry.
AB  - A method using ion chromatography-inductively coupled plasma-mass spectrometry
      (IC-ICP-MS) for the quantification of arsenic species in fruit juices has been
      developed and validated. The method is capable of quantifying four anionic
      arsenic species - arsenite (As(III)), arsenate (As(V)), dimethylarsinic acid
      (DMA) and monomethylarsonic acid (MMA) - in the presence of unretained species
      such as arsenobetaine (AsB). Method validation was based on repeatability,
      analysis of reference materials, recovery of fortified samples, and determination
      of detection and quantification limits. The method was tested for use with apple,
      pear, cranberry, grape (red, white and purple) juices, as well as several juice
      blends. Limits of detection were 0.35, 0.41, 0.45 and 0.70 ug kg-1 for As(III),
      DMA, MMA and As(V), respectively. Chromatographic recovery was good for most
      samples (90-107% compared to total arsenic), though recovery for some grape juice
      samples was lower (67-78%).

PMID- 22639851
TI  - Effects of some anti-neoplastic drugs on sheep liver sorbitol dehydrogenase.
AB  - Stress is an important factor for many diseases in living metabolisms. The mini
      pathway named as polyol is a critical junction for stress factors. This pathway
      has two enzymes: aldose reductase (AR) and sorbitol dehydrogenase (SDH). It is
      linked with some diseases such as diabetes mellitus and some cancer types. In
      particular, SDH is very sensitive and unstable in in vitro conditions. In this
      study, SDH was purified by using simple and rapid chromatographic methods such as
      DEAE-Sephadex and CM-Sephadex C-50 columns. Subunit and active form molecular
      weights were found as 39.8 kDa and 150 kDa, respectively. The in vitro effects of
      some antineoplastic drugs were investigated. IC(50) values were 0.025, 0.081,
      0.291, 1.62, 4.86, 6.54 mM for dacarbazine, methotrexate, epirubicin
      hydrochloride, calcium folinate, gemcitabine hydrochloride, oxaliplatin,
      respectively. From these results, dacarbazine was lowest IC(50) value and it is
      the strongest inhibitor for liver SDH enzyme activity compared to the other
      drugs.

PMID- 22639852
TI  - First step in the differential diagnosis of folliculitis: cytology.
AB  - Folliculitis is a superficial inflammation of the hair follicles, and can be
      observed in individuals of any age or race. The incidence of folliculitis is
      unknown because most patients only consult a doctor in cases of increasing
      lesions. There are various infectious and non-infectious causes of folliculitis,
      and the most common causative agent is Staphylococcus aureus. In addition,
      several Gram-negative bacterial, fungal, parasitic, and viral pathogens can cause
      follicular papules and pustules. In routine practice, however, these lesions are
      usually thought to be bacterial. Therefore, topical and/or systemic antibacterial
      treatment is recommended, but this involves the risk of being misused for months
      or even years. Cytology, a simple, rapid, inexpensive, and repeatable diagnostic
      method, can reveal various bacterial, fungal, viral, and parasitic pathogens.
      This review discusses the use of clinical sampling and staining of cytologic
      samples for the differential diagnosis of folliculitis, cytologic findings, and
      the frequency with which dermatologists use cytology to diagnose folliculitis,
      particularly in the age of molecular biology and more expensive, sophisticated
      investigations.

PMID- 22639853
TI  - Reduction in fat uptake of doughnut by microparticulated wheat bran.
AB  - Wheat flour-microparticulated wheat bran (MWB) mixture and composites were
      prepared, and their potential as an oil repellent was evaluated in doughnuts. As
      MWB content increased, the oil-holding capacity decreased, and there were
      significant changes in water-holding capacity (p < 0.05). As MWB content
      increased, the fat content of doughnuts decreased. In addition, the wheat flour
      MWB composite was more effective for preventing fat uptake than the wheat flour
      MWB mixture. The hardness of the composite was higher than the mixture, although
      volume and weight decreased and surface colour became darker than that of the
      mixture. As the proportion of wheat bran in the doughnut formulation increased,
      the inner crust achieved a uniform cell size and cellular integrity was improved.
      Based on these data, wheat flour-MWB composites are appropriate for use in
      doughnut formulas with low fat uptake.

PMID- 22639854
TI  - Steatocystoma multiplex: keratin 17 - the key player?

PMID- 22639855
TI  - Analysis of F9 point mutations and their correlation to severity of haemophilia B
      disease.
AB  - Haemophilia B is an X-linked recessive disorder caused by deficiency of
      functional coagulation factor IX, which results almost exclusively from mutations
      in the F9 gene. We sought to determine features, which could distinguish between
      mutations that cause severe disease symptoms from those that cause non-severe
      disease symptoms. Towards this objective, we have performed a statistical
      analysis of reported point mutations in F9. These include: potential local
      changes in mRNA free energy, codon usage, charge and type of mutated amino acid,
      location of the mutation with regard to protein secondary structure and
      functional domain and amino acids' evolutionary conservation scores. Wilcoxon
      signed-rank tests showed highly significant differences between severe and non
      severe disease causing mutations in their effect on free energy of small mRNA
      fragments and evolutionarily conserved amino acids. Our results suggest that
      information at the mRNA level as well as conservation of the amino acid correlate
      well with disease severity. This study demonstrates that computational tools may
      be used to characterize the severity of haemophilia B associated with point
      mutations and suggests their utility in predicting the outcome of sequence
      changes in recombinant proteins.

PMID- 22639856
TI  - Diagnostic performance of handheld echocardiography for the assessment of basic
      cardiac morphology and function: a validation study in routine cardiac patients.
AB  - AIMS: To investigate the intra- and interrater variability of expert users in the
      interpretation of handheld echocardiographic studies (HAND). METHODS: We scanned
      320 consecutive patients with both HAND and high-end (HIGH) scanners. Images were
      interpreted independently by two blinded level III echocardiographers. Readings
      from the HIGH scanner served as the gold standard. Segmental endocardial-border
      delineation was scored to describe image quality. Assessment of left ventricular
      (LV) dimensions and regional/global LV function, and grading of valve disease
      were compared. RESULTS: We obtained correlations of r > 0.8 (P < 0.01) for
      intrarater variability for both expert readers when they analyzed HAND and HIGH
      images in relation to image quality, wall-motion abnormalities, and LV
      measurements. For intrarater variability of LVEF assessment, the correlations
      were at least moderate (r > 0.6, P < 0.01). Interrater variability for HIGH
      images was r = 0.9 (P < 0.01) for all parameters. Interrater variability for HAND
      images was less favorable for all parameters, but was at least moderate (r > 0.6,
      P < 0.01). All cases of pericardial effusion were detected. The agreement for the
      detection and grading of mitral and aortic regurgitation was at least moderate
      (kappa > 0.6, P < 0.01). Detection of tricuspid regurgitation was less favorable,
      but only cases of mild regurgitation were missed. All cases of aortic stenosis
      were detected by both echocardiographers. CONCLUSIONS: In relation to the basic
      assessment of cardiac morphology and function, the interpretation by experienced
      echocardiographers of images obtained using handheld echocardiographic devices
      showed a moderate to very good correlation with standard echocardiography.

PMID- 22639857
TI  - Childhood pityriasis lichenoides and oral erythromycin.
AB  - Pityriasis lichenoides (PL) is not uncommon in childhood, but current knowledge
      about the efficacy of oral erythromycin therapy for its treatment in children is
      limited. To investigate the role of oral erythromycin therapy in the treatment of
      PL in children, the records of 24 children with PL who had been started on oral
      erythromycin treatment at our institution between 2005 and 2008 were
      retrospectively reviewed. The study included 24 patients (14 male, 10 female)
      with a median age of 7 years (range 2-14) of whom 15 (62.5%) had PL chronica
      (PLC), six (25%) PL et varioliformis acuta (PLEVA), and three (2.5%) PLEVA-PLC
      overlap. History of upper respiratory tract infection was reported in 33% (n = 8)
      of the patients. History of drug intake and vaccination was noted in 20% (n = 5)
      and 20% (n = 5), respectively. The disease began during spring (30%, n = 7) or
      fall (30%, n = 7) in the majority of patients. The median duration of the disease
      was 11 months (range 1-48 months). Fifteen (68.2%) patients had more than 100
      lesions. Distribution was diffuse in 82% (n = 18) of the cases and peripheral in
      the remainder (n = 6). Oral erythromycin was started at a dosage of 30 to 50
      mg/kg per day in three to four divided dosages for 1 to 4 months. Good response
      was recorded in 64% and 73% of patients in the first and second months of
      therapy, respectively. Response rate rose to 83% in the third month. In those for
      whom follow-up data were available (n = 16), relapse was recorded in 12.5% (n =
      3). Oral erythromycin may be an effective and well-tolerated treatment option for
      PL in children and should be continued for at least 3 months.

PMID- 22639858
TI  - The latitudinal gradient in dispersal constraints: ecological specialisation
      drives diversification in tropical birds.
AB  - Physiological and behavioural constraints arising from ecological specialisation
      are proposed to limit gene flow and promote diversification in tropical lineages.
      In this study, we use phylogenetic analyses to test this idea in 739 Amazonian
      bird species. We show that patterns of species and subspecies richness are best
      predicted by a suite of avian specialisms common in tropical avifaunas but rare
      in the temperate zone. However, this only applied to niche traits associated with
      dispersal limitation rather than vagility. These findings are consistent with the
      view that diversity is promoted by more finely partitioned niches, although not
      simply by coevolutionary adaptation and niche packing as is often assumed.
      Instead, they suggest that diversification is driven by dispersal constraints,
      and that niches characterised by these constraints are biased towards tropical
      systems. We conclude that specialised tropical niches reduce the likelihood of
      dispersal across barriers, thereby increasing allopatric diversification and
      contributing to the latitudinal diversity gradient.

PMID- 22639859
TI  - Clinical utility of serum fucosylated hemopexin in Japanese patients with
      hepatocellular carcinoma.
AB  - AIM:   Hepatocellular carcinoma (HCC) is a common clinical problem all over the
      world. Fucosylated hemopexin (Fuc-Hpx) is a newly reported glycoprotein for the
      diagnosis of HCC, however, its clinical implications are unclear. The aim of this
      study was to elucidate the clinical utility of Fuc-Hpx in Japanese patients with
      HCC. METHODS:   The sera from 331 HCC patients, 45 with liver cirrhosis (LC), 85
      with chronic hepatitis (CH) and 22 healthy people were examined for the
      expression of Fuc-Hpx; the level was compared with clinical parameters as well as
      hemopexin (Hpx) expression. The expressions of Fuc-Hpx in 12 HCC tissues and
      corresponding adjacent non-cancerous liver tissues were also examined. RESULTS:  
      No correlation was observed between Hpx and Fuc-Hpx level. The median Fuc-Hpx
      levels in healthy people and CH, LC and HCC patients were 3.8, 3.7, 6.1 and 7.6
      AU/mL, respectively (CH vs LC, P = 0.002; CH vs HCC, P < 0.001; LC vs HCC, P =
      0.02). Multivariate analysis revealed that low albumin, low prothrombin time and
      the presence of HCC were significantly correlated with high Fuc-Hpx (P = 0.013,
      =0.001 and <0.001, respectively). Among the HCC patients, albumin was correlated
      with high Fuc-Hpx; however, none of the tumor factors, such as tumor size, tumor
      number and tumor stage, was correlated with Fuc-Hpx level. The expression of Fuc
      Hpx in cancer tissue was not different from that in non-cancerous tissue.
      CONCLUSION:   Fuc-Hpx is a valuable biomarker for HCC but it might be a marker
      for hypercarcinogenic liver rather than a marker for tumor-bearing liver.

PMID- 22639860
TI  - Population-based comparative effectiveness of nephron-sparing surgery vs ablation
      for small renal masses.
AB  - OBJECTIVE: To determine, in a population-based cohort, if disease-specific
      survival (DSS) was equivalent in patients undergoing ablation vs nephron-sparing
      surgery (NSS) for clinical stage T1a renal cell carcinoma (RCC). PATIENTS AND
      METHODS: A retrospective cohort study was performed using patients from the
      Surveillance, Epidemiology and End Results cancer registry with RCC < 4 cm and no
      evidence of distant metastases, who underwent ablation or NSS. Kaplan-Meier and
      Cox regression analyses were performed to determine if treatment type was
      independently associated with DSS. RESULTS: Between 1998 and 2007, a total of
      8818 incident cases of RCC were treated with either NSS (7704) or ablation
      (1114). The median (interquartile range) follow-up was 2.8 (1.2-4.7) years in the
      NSS group and 1.6 (0.7-2.9) years in the ablation group, although 10% of each
      cohort were followed up beyond 5 years. After multivariable adjustment, ablation
      was associated with a twofold greater risk of kidney cancer death than NSS
      (hazard ratio 1.9, 95% confidence interval 1.1-3.3, P= 0.02). Age, gender,
      marital status and tumour size were also significantly associated with outcome.
      The predicted probability of DSS at 5 years was 98.3% with NSS and 96.6% with
      ablation. CONCLUSION: After controlling for age, gender, marital status and
      tumour size, the typical patient presenting with clinical stage T1a RCC, who
      undergoes ablation rather than NSS, has a twofold increase in the risk of kidney
      cancer death; however, at 5 years the absolute difference is small, and may only
      be realized by patients with long life expectancies.

PMID- 22639861
TI  - Glutathione S-transferase Pi expression predicts response to adjuvant
      chemotherapy for stage C colon cancer: a matched historical control study.
AB  - BACKGROUND: This study examined the association between overall survival and
      Glutathione S-transferase Pi (GST Pi) expression and genetic polymorphism in
      stage C colon cancer patients after resection alone versus resection plus 5
      fluourouracil-based adjuvant chemotherapy. METHODS: Patients were drawn from a
      hospital registry of colorectal cancer resections. Those receiving chemotherapy
      after it was introduced in 1992 were compared with an age and sex matched control
      group from the preceding period. GST Pi expression was assessed by
      immunohistochemistry. Overall survival was analysed by the Kaplan-Meier method
      and Cox regression. RESULTS: From an initial 104 patients treated with
      chemotherapy and 104 matched controls, 26 were excluded because of non
      informative immunohistochemistry, leaving 95 in the treated group and 87
      controls. Survival did not differ significantly among patients with low GST Pi
      who did or did not receive chemotherapy and those with high GST Pi who received
      chemotherapy (lowest pair-wise p = 0.11) whereas patients with high GST Pi who
      did not receive chemotherapy experienced markedly poorer survival than any of the
      other three groups (all pair-wise p <0.01). This result was unaffected by GST Pi
      genotype. CONCLUSION: Stage C colon cancer patients with low GST Pi did not
      benefit from 5-fluourouracil-based adjuvant chemotherapy whereas those with high
      GST Pi did.

PMID- 22639862
TI  - Impaired glucose tolerance during pregnancy: possible risk factor for
      vaginal/anorectal colonization by Group B Streptococcus.

PMID- 22639863
TI  - Investigating the predictive validity of implicit and explicit measures of
      motivation in problem-solving behavioural tasks.
AB  - Research into the effects of individuals'autonomous motivation on behaviour has
      traditionally adopted explicit measures and self-reported outcome assessment.
      Recently, there has been increased interest in the effects of implicit
      motivational processes underlying behaviour from a self-determination theory
      (SDT) perspective. The aim of the present research was to provide support for the
      predictive validity of an implicit measure of autonomous motivation on
      behavioural persistence on two objectively measurable tasks. SDT and a dual
      systems model were adopted as frameworks to explain the unique effects offered by
      explicit and implicit autonomous motivational constructs on behavioural
      persistence. In both studies, implicit autonomous motivation significantly
      predicted unique variance in time spent on each task. Several explicit measures
      of autonomous motivation also significantly predicted persistence. Results
      provide support for the proposed model and the inclusion of implicit measures in
      research on motivated behaviour. In addition, implicit measures of autonomous
      motivation appear to be better suited to explaining variance in behaviours that
      are more spontaneous or unplanned. Future implications for research examining
      implicit motivation from dual-systems models and SDT approaches are outlined. 

PMID- 22639865
TI  - A stable intermediate wetting state after a water drop contacts the bottom of a
      microchannel or is placed on a single corner.
AB  - It is considered that, after a water drop contacts the base of a roughness
      groove, water should immediately fill this roughness groove. Subsequently, Cassie
      Baxter wetting state is transited to that of Wenzel. Accordingly, one of the
      criteria used to judge the transition from Cassie-Baxter to Wenzel states is
      whether a water drop has contact with the base of a roughness groove. In this
      work, through theoretical and experimental investigations, we show that this
      transition criterion does not always hold true in the case of microchannels. We
      first theoretically prove that, when an angle criterion is satisfied, there may
      exist an intermediate wetting state inside a microchannel after a water drop
      contacts the bottom of the microchannel. In this wetting state, water does not
      completely fill the microchannel, and air pockets still exist in its bottom
      corners. Also, the wetting state is stable in the sense that its energy state is
      lower than that of the Wenzel model. According to the angle criterion, such
      intermediate states may exist, for example, in microchannels with vertical
      sidewalls, when contact angles on the inner surfaces of these microchannels are
      larger than 135 degrees . In addition to microchannels, the aforementioned
      intermediate state may also exist on a single corner (which is formed by a
      horizontal plate and an inclined plate), when the angle criterion is met. After
      theoretical modeling, we then conduct four types of tests on single corners and
      microchannels to validate the angle criterion. In these tests, once the angle
      criterion is met, stable intermediate states are observed on the corresponding
      samples. In addition, it is found from the two types of tests conducted on
      microchannels that, once Laplace pressure inside a water drop is gradually
      reduced, such an intermediate wetting state may be transited back to the original
      Cassie-Baxter state. On the other hand, the Wenzel state may not have such a
      reversal transition unless an additional force is applied to overcome energy
      barrier between Wenzel and Cassie-Baxter states.

PMID- 22639864
TI  - The effect of taping versus semi-rigid bracing on patient outcome and
      satisfaction in ankle sprains: a prospective, randomized controlled trial.
AB  - BACKGROUND: Functional treatment is a widely used and generally accepted
      treatment for ankle sprain. A meta-analysis comparing the different functional
      treatment options could not make definitive conclusions regarding the
      effectiveness, and until now, little was known about patient satisfaction in
      relation to the outcome. METHODS: Patients with acute ankle sprain received rest,
      ice, compression and elevation with an compressive bandage at the emergency
      department. After 5-7 days, 100 patients with grade II and III sprains were
      randomized into two groups: one group was treated with tape and the other with a
      semi-rigid ankle brace, both for 4 weeks. Post-injury physical and proprioceptive
      training was standardized. As primary outcome parameter patient satisfaction and
      skin complications were evaluated using a predefined questionnaire and numeric
      rating scale. As secondary outcome parameter the ankle joint function was
      assessed using the Karlsson scoring scale and range of motion. RESULTS: Patient
      reported comfort and satisfaction during treatment with a semi-rigid brace was
      significantly increased. The rate of skin complication in this group was
      significantly lower compared to the tape group (14.6% versus 59.1%, P < 0.0001).
      Functional outcome of the ankle joint was similar between the two treatment
      groups, as well as reported pain. CONCLUSION: Treatment of acute ankle sprain
      with semi-rigid brace leads to significantly higher patient comfort and
      satisfaction, both with similar good outcome.

PMID- 22639866
TI  - Mild activation of poly(ADP-ribose) polymerase (PARP) is neuroprotective in rat
      hippocampal slice models of ischemic tolerance.
AB  - Ischemic tolerance is a phenomenon in which exposure to a mild preconditioning
      stress results in resistance to a subsequent lethal ischemic insult. Here we
      investigated the role of poly(ADP-ribose) polymerase (PARP) in the development of
      ischemic tolerance by using organotypic rat hippocampal slices exposed to 30 min
      oxygen-glucose deprivation (OGD), which leads to selective injury of the CA1
      subregion 24 h later. We developed models of pharmacological preconditioning by
      exposing slices to subtoxic concentrations of either N-methyl-D-aspartate (NMDA)
      or (S)-3,5-dihydroxyphenylglycine (DHPG) and then, 24 h later, to 30 min OGD.
      Under these conditions, we observed a significant reduction in OGD-induced CA1
      damage. Exposure of slices to the PARP-1 and -2 inhibitors TIQ-A, PJ-34 and UPF
      1069 during preconditioning prevented the development of OGD tolerance in a
      concentration-dependent manner. NMDA and DHPG preconditioning increased the
      activity of PARP, as detected by immunoblots using antibodies against the
      poly(ADP-ribose) polymer product, but was not associated with consumption of
      cellular NAD(+) or ATP. Neuroprotection induced by preconditioning was also
      prevented by the caspase inhibitor Z-VAD-FMK. The modest but significant increase
      in caspase-3/7 induced by preconditioning, however, was not associated with PARP
      1 cleavage, as occurred with staurosporine. Finally, TIQ-A prevented the
      activation of ERK1/2 and Akt induced by NMDA preconditioning, suggesting that the
      protective mechanism evoked by PARP requires activation of these prosurvival
      mediators. Our results suggest that preconditioning with appropriate
      pharmacological stimuli may promote neuroprotective mechanisms triggered by the
      sublethal activation of two otherwise deleterious executioners such as PARP and
      caspase-3/7.

PMID- 22639868
TI  - The effect of close relatives on unsupervised Bayesian clustering algorithms in
      population genetic structure analysis.
AB  - The inference of population genetic structures is essential in many research
      areas in population genetics, conservation biology and evolutionary biology.
      Recently, unsupervised Bayesian clustering algorithms have been developed to
      detect a hidden population structure from genotypic data, assuming among others
      that individuals taken from the population are unrelated. Under this assumption,
      markers in a sample taken from a subpopulation can be considered to be in Hardy
      Weinberg and linkage equilibrium. However, close relatives might be sampled from
      the same subpopulation, and consequently, might cause Hardy-Weinberg and linkage
      disequilibrium and thus bias a population genetic structure analysis. In this
      study, we used simulated and real data to investigate the impact of close
      relatives in a sample on Bayesian population structure analysis. We also showed
      that, when close relatives were identified by a pedigree reconstruction approach
      and removed, the accuracy of a population genetic structure analysis can be
      greatly improved. The results indicate that unsupervised Bayesian clustering
      algorithms cannot be used blindly to detect genetic structure in a sample with
      closely related individuals. Rather, when closely related individuals are
      suspected to be frequent in a sample, these individuals should be first
      identified and removed before conducting a population structure analysis.

PMID- 22639867
TI  - Cyclic Vomiting Syndrome (CVS): is there a difference based on onset of symptoms-
      pediatric versus adult?
AB  - BACKGROUND: Cyclic Vomiting Syndrome (CVS) is a well-recognized functional
      gastrointestinal disorder in children but its presentation is poorly understood
      in adults. Genetic differences in pediatric-onset (presentation before age 18)
      and adult-onset CVS have been reported recently but their clinical features and
      possible differences in response to therapy have not been well studied. METHODS:
      This was a retrospective review of 101 CVS patients seen at the Medical College
      of Wisconsin between 2006 and 2008. Rome III criteria were utilized to make the
      diagnosis of CVS. RESULTS: Our study population comprised of 29(29%) pediatric
      onset and 72 (71%) adult-onset CVS patients. Pediatric-onset CVS patients were
      more likely to be female (86% vs. 57%, p = 0.005) and had a higher prevalence of
      CVS plus (CVS + neurocognitive disorders) as compared to adult-onset CVS patients
      (14% vs. 3%, p = 0.05). There was a longer delay in diagnosis (10 +/- 7 years) in
      the pediatric-onset group when compared to (5 +/- 7 years) adult-onset CVS group
      (p = 0.001). Chronic opiate use was less frequent in the pediatric-onset group
      compared to adult-onset patients (0% vs. 23%, p = 0.004). Aside from these
      differences, the two groups were similar with regards to their clinical features
      and the time of onset of symptoms did not predict response to standard treatment.
      The majority of patients (86%) responded to treatment with tricyclic
      antidepressants, anticonvulsants (topiramate), coenzyme Q-10, and L-carnitine.
      Non-response to therapy was associated with coalescence of symptoms, chronic
      opiate use and more severe disease as characterized by longer episodes, greater
      number of emergency department visits in the year prior to presentation, presence
      of disability and non-compliance on univariate analysis. On multivariate
      analysis, only compliance to therapy was associated with a response. (88% vs.
      38%, Odds Ratio, OR 9.6; 95% Confidence Interval [CI], 1.18-77.05). CONCLUSION:
      Despite reported genetic differences, the clinical features and response to
      standard therapy in pediatric- and adult-onset CVS were mostly similar. Most
      patients (86%) responded to therapy and compliance was the only factor associated
      with a response.

PMID- 22639869
TI  - Developmental venous anomalies--two cases with venous thrombosis.
AB  - Developmental venous anomalies (DVA) are generally considered the most common
      vascular anomalies. They are usually asymptomatic and display a benign clinical
      course. We report two cases of thrombosed developmental venous anomalies. Both
      patients developed venous infarcts with haemorrhagic transformation from the
      thrombosed DVA, and 1 patient needed decompressive craniectomy.

PMID- 22639871
TI  - Rhamnosylation: diastereoselectivity of conformationally armed donors.
AB  - The alpha/beta-selectivity of super-armed rhamnosyl donors have been investigated
      in glycosylation reactions. The solvent was found to have a minor influence,
      whereas temperature was crucial for the diastereoselectivity. At very low
      temperature, a modest beta-selectivity could be obtained, and increasing
      temperature gave excellent alpha-selectivity. The donors were highly reactive,
      and activation was observed at temperatures as low as -107  degrees C. Different
      promoter systems and leaving groups were investigated, and only activation with a
      heterogeneous catalyst increased the amount of the beta-anomer significantly. By
      introducing an electron-withdrawing nonparticipating group, benzyl sulfonyl, on 2
      O, an increase in beta-product was observed.

PMID- 22639870
TI  - Stimulation of the D5 dopamine receptor acidifies the lysosomal pH of retinal
      pigmented epithelial cells and decreases accumulation of autofluorescent
      photoreceptor debris.
AB  - Optimal neuronal activity requires that supporting cells provide both efficient
      nutrient delivery and waste disposal. The incomplete processing of engulfed waste
      by their lysosomes can lead to accumulation of residual material and compromise
      their support of neurons. As most degradative lysosomal enzymes function best at
      an acidic pH, lysosomal alkalinization can impede enzyme activity and increase
      lipofuscin accumulation. We hypothesize that treatment to reacidify compromised
      lysosomes can enhance degradation. Here, we demonstrate that degradation of
      ingested photoreceptor outer segments by retinal pigmented epithelial cells is
      increased by stimulation of D5 dopamine receptors. D1/D5 receptor agonists
      reacidified lysosomes in cells alkalinized by chloroquine or tamoxifen, with
      acidification dependent on protein kinase A. Knockdown with siRNA confirmed
      acidification was mediated by the D5 receptor. Exposure of cells to outer
      segments increased lipofuscin-like autofluorescence, but SKF 81297 reduced
      autofluorescence. Likewise, SKF 81297 increased the activity of lysosomal
      protease cathepsin D in situ. D5DR stimulation also acidified lysosomes of
      retinal pigmented epithelial cells from elderly ABCA4(-/-) mice, a model of
      recessive Stargardt's retinal degeneration. In conclusion, D5 receptor
      stimulation lowers compromised lysosomal pH, enhancing degradation. The reduced
      accumulation of lipofuscin-like autofluorescence implies the D5 receptor
      stimulation may enable cells to better support adjacent neurons.

PMID- 22639872
TI  - Tissue Doppler time intervals predict the occurrence of rehospitalization in
      chronic heart failure: data from the daunia heart failure registry.
AB  - BACKGROUND: Patients with chronic heart failure (HF) are often rehospitalized;
      rehospitalization identifies subjects with a poorer quality of life and a worse
      prognosis. Estimates of the time intervals by tissue Doppler imaging (TDI) in
      patients with chronic HF has not been fully investigated, despite recent studies
      having explored the prognostic role of TDI-derived parameters in major cardiac
      diseases, such as HF. We, therefore, aimed to assess the prognostic value of time
      intervals evaluated by TDI in patients with chronic HF. METHODS: A total of 249
      patients with chronic HF enrolled in the Daunia Heart Failure Registry underwent
      echocardiography assessment and were followed prospectively for a mean 284 +/-
      210 days. Conventional echocardiography and TDI parameters were calculated; time
      intervals were calculated by TDI: ST (systolic time), ET (ejection time), FT
      (filling time), and ICT (isovolumic contraction time). We also have calculated
      ICT/ET and tissue myocardial performance index ([ICT+IRT]/ET). RESULTS: At
      univariate analysis, ET (RR: 0.80, 95% confidence interval [CI] 0.71-0.90, P <
      0.001), ST (RR: 0.88, 95% CI 0.78-0.99, P < 0.05), FT (RR: 0.88, 95% CI 0.78
      0.99, P < 0.05), ICT/ET (RR: 1.21, 95% CI 1.07-1.37, P < 0.01) were related to
      the occurrence of rehospitalization during follow-up. At multivariate Cox
      regression analysis, correlations remained significant for ET and ST (P < 0.05
      and P < 0.01, respectively). CONCLUSIONS: Time intervals assessed by TDI may be
      helpful in predicting the risk of rehospitalization in subjects with chronic HF.

PMID- 22639873
TI  - Zonisamide monotherapy for idiopathic epilepsy in dogs.
AB  - AIM: To evaluate the efficacy of zonisamide as a monotherapy in dogs with
      idiopathic epileptic seizure. METHODS: The experiment was conducted on 10 dogs
      with idiopathic epilepsy that were treated at the Seoul National University
      Hospital for Animals. A diagnosis was conducted based on physical and neurologic
      examination, complete blood count and chemical analysis, magnetic resonance
      imaging and cerebrospinal fluid analyses. Idiopathic epilepsy was diagnosed when
      all of these examinations were normal. Oral zonisamide was administrated to 10
      dogs with idiopathic epilepsy at 5-15 mg/kg per os every 12 h to achieve a
      concentration of zonisamide in serum of 10-40 MUg/mL. The frequency of seizures
      before and after the administration of zonisamide therapy was recorded and the
      concentrations of zonisamide in serum were measured. RESULTS: Six (60%) of the
      dogs were favourable responders to treatment, showing a >=50% reduction in
      monthly frequency of seizures. Of the remaining four, two dogs did not show a
      reduction and the other two showed an increase in frequency of seizures. The mean
      dosage of zonisamide for favourable responders was 7.92 (SD 3.79) mg/kg, which
      was administered orally twice a day. Only one dog, which was one of the
      unfavourable responders in the whole study, experienced mild side effects.
      CONCLUSIONS: Among the dogs treated with oral zonisamide, 60% responded
      favourably. The effect of zonisamide as an anticonvulsant drug was demonstrated
      in this study. CLINICAL RELEVANCE: Based on these results, zonisamide monotherapy
      is effective in some dogs with idiopathic epilepsy.

PMID- 22639874
TI  - The role of prior corticosteroid use on the clinical course of Stevens-Johnson
      syndrome and toxic epidermal necrolysis: a case-control analysis of patients
      selected from the multinational EuroSCAR and RegiSCAR studies.
AB  - BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are immunologically mediated, severe cutaneous adverse reactions involving
      cytotoxic T cells, natural killer cells and various mediators. In large studies,
      up to 15% of SJS/TEN occurred in patients with chronic corticosteroid use. It is
      unclear if this prior exposure to corticosteroids modified the disease course.
      OBJECTIVES: To evaluate whether systemic corticosteroid usage prior to the onset
      of SJS/TEN modified the clinical course and outcome. If a disease-modifying
      effect is present, information from such an analysis may have implications on the
      therapeutic use of corticosteroids in SJS/TEN. METHODS: This is a case-control
      study based on data collected in the EuroSCAR and RegiSCAR studies. Ninety-two
      cases of SJS/TEN with exposure to corticosteroids prior to the onset of disease,
      and 321 randomly selected SJS/TEN patients without prior exposure were included.
      Primary outcomes included progression of disease, disease severity and mortality.
      A secondary analysis of latency between the beginning of drug use and the onset
      of disease, based on exposure to a single high-risk drug, was also performed.
      RESULTS: On multivariate analysis, cases with prior exposure to corticosteroids
      had a longer progression of disease by 2.2 days [95% confidence interval (CI) 1.1
      3.2]. The disease severity and mortality outcome were unaffected. In addition,
      there is evidence that corticosteroids delayed the onset of SJS/TEN in patients
      with exposure to high-risk drugs by 7.1 days (CI -0.2 to 14.5). CONCLUSIONS: The
      prior use of corticosteroids prolonged the period of disease progression without
      influencing the disease severity or mortality. In addition, when SJS/TEN is
      preceded by use of a single high-risk drug, the latency between the drug intake
      and the onset of SJS/TEN may also be increased. These findings suggest that
      corticosteroids have a mild impact on the course of SJS/TEN, and further studies
      are required to clarify any potential therapeutic effects.

PMID- 22639875
TI  - Antimicrobial resistance of emerging foodborne pathogens: status quo and global
      trends.
AB  - Emerging foodborne pathogens are challenging subjects of food microbiology with
      their antibiotic resistance and their impact on public health. Campylobacter
      jejuni, Salmonella spp. and Verotoxigenic Escherichia coli (VTEC) are significant
      emerging food pathogens, globally. The decrease in supply and increase in demand
      lead developed countries to produce animal products with a higher efficiency. The
      massive production has caused the increase of the significant foodborne diseases.
      The strict control of food starting from farm to fork has been held by different
      regulations. Official measures have been applied to combat these pathogens. In
      2005 EU declared that, an EU-wide ban on the use of antibiotics as growth
      promoters in animal feed would be applied on 1 January 2006. The ban is the final
      step in the phasing out of antibiotics used for non-medical purposes. It is a
      part of the Commission's strategy to tackle the emergence of bacteria and other
      microbes resistant to antibiotics, due to their overexploitation or misuse. As
      the awareness raises more countries banned application of antibiotics as growth
      promoter, but the resistance of the emerging foodborne pathogens do not represent
      decrease. Currently, the main concern of food safety is counter measures against
      resistant bugs.

PMID- 22639876
TI  - Intermediate fragmentation per se provides stable predator-prey metapopulation
      dynamics.
AB  - The extent to which a landscape is fragmented affects persistence of predator
      prey dynamics. Increasing fragmentation concomitantly imposes conditions that
      stabilise and destabilise metapopulations. For the first time, we explicitly
      assessed the hypothesis that intermediate levels provide optimal conditions for
      stability. We examine four structural changes arising from increased
      fragmentation: increased fragment number; decreased fragment size; increased
      connectedness (corridors scaled to fragment); increased fragment heterogeneity
      (based on connectedness). Using the model predator-prey system (Didinium
      Paramecium) we support our hypothesis, by examining replicated metapopulations
      dynamics at five fragmentation levels. Although both species became extinct
      without fragmentation, prey survived at low and high levels, and both survived at
      intermediate levels. By examining time to extinction, maximum abundances, and
      population asynchrony we conclude that fragmentation produces structural
      heterogeneity (independent of environmental heterogeneity), which influences
      stability. Our analysis suggests why some theoretical, field and microcosm
      studies present conflicting views of fragmentation effects on population
      persistence.

PMID- 22639877
TI  - Whipple disease mimicking adult-onset Still's disease and treated by anakinra:
      diagnosis using PCR.

PMID- 22639878
TI  - Exogenous nitric oxide negatively regulates the S-nitrosylation p38 mitogen
      activated protein kinase activation during cerebral ischaemia and reperfusion.
AB  - AIMS: A number of studies have suggested that nitric oxide (NO) plays an
      important role in the reactive phosphorylation of p38MAPKalpha (p38). However,
      whether S-nitrosylation of p38 is activated by NO and the details remain unclear.
      The aim of the present work was to assess the activation of p38, the S
      nitrosylation site and the p38 signalling pathway in rat hippocampus and in
      HEK293 cell induced by exogenous NO. METHODS: Primary hippocampal cultures,
      HEK293 cells and rat model of cerebral ischaemia/reperfusion (brain ischaemia was
      induced by four-vessel occlusion procedure) were used in this study. Biotin
      switch method and immunoblotting were performed to study the S-nitrosylation and
      phosphorylation of p38, and neuronal loss was observed by histology. RESULTS:
      Endogenous NO increased p38 phosphorylation and S-nitrosylation, and the
      activation of p38 was dependent on the S-nitrosylation of Cys-211, which was
      critical for the NO-mediated activation of p38. The exogenous NO donor sodium
      nitroprusside, S-nitrosoglutathione, 7-nitroindazole, the inhibitor of the
      neuronal nitric oxide synthase, inhibited the activation of p38 signal pathway
      induced by cerebral ischaemia/reperfusion and attenuated the damage in rat
      hippocampal neurones. Moreover, the N-methyl-D-aspartate receptor (NMDAR) is
      probably involved in the p38 activation process of S-nitrosylation and
      phosphorylation. CONCLUSION: Endogenous NO induces the S-nitrosylation and
      phosphorylation of p38 and mediates p38 signalling pathway by NMDAR, and as
      exogenous NO inhibits this process and is neuroprotective in rat cerebral
      ischaemia/reperfusion, it may make a contribution to stroke therapy.

PMID- 22639879
TI  - Feasibility of using thrombin generation assay (TGA) for monitoring of
      haemostasis during supplementation therapy in haemophilic patients without
      inhibitors.
AB  - Monitoring factor replacement treatment and observing concordance with clinical
      haemostasis is crucial in vital haemorrhages and major surgeries in haemophilic
      patients. We aimed to investigate the value of the thrombin generation assay
      (TGA) and thromboelastography (TEG) for monitoring haemostasis in haemophilic
      patients during factor replacement treatment. The study group consisted of 29
      patients (21 haemophilia A, 8 haemophilia B). All the patients FVIII-inhibitor
      were negative. A total of 35 bleeding episodes and/or surgical interventions were
      evaluated. aPTT, FVIII/FIX activity, TEG and TGA tests were conducted before and
      after factor therapy during the bleeding episode or surgical prophylaxis of
      haemophilic patients. Correlations among these tests were evaluated and compared
      with clinical responses. No correlation was found among aPTT, factor activities
      and clinical outcome. There were also no correlation found between TEG parameters
      and clinical outcome. The only significant correlation found between TGA
      parameters and clinical outcome was the correlation between peak thrombin. In
      conclusion, we found superiority of TGA-peak thrombin over other traditional
      tests for monitoring haemostasis in haemophilic patients in this study.

PMID- 22639880
TI  - Dermoscopy distinction of eruptive vellus hair cysts with molluscum contagiosum
      and acne lesions.
AB  - Eruptive vellus hair cysts are benign lesions that can be difficult to
      distinguish from other skin conditions, including molluscum contagiosum and acne
      vulgaris. Diagnosis can be corroborated with histopathology. We emphasize
      differing dermoscopy features to help distinguish eruptive vellus hair cysts from
      molluscum contagiosum or acne.

PMID- 22639881
TI  - Azobenzene-containing molecularly imprinted polymer microspheres with photo- and
      thermoresponsive template binding properties in pure aqueous media by atom
      transfer radical polymerization.
AB  - A facile, general, and highly efficient approach to obtain azobenzene (azo)
      containing molecularly imprinted polymer (MIP) microspheres with both photo- and
      thermoresponsive template binding properties in pure aqueous media is described
      for the first time, which involves the first synthesis of "living" azo-containing
      MIP microspheres with surface-immobilized alkyl halide groups via atom transfer
      radical precipitation polymerization (ATRPP) and their subsequent modification
      via surface-initiated atom transfer radical polymerization (ATRP) of N
      isopropylacrylamide (NIPAAm). The successful grafting of poly(NIPAAm) (PNIPAAm)
      brushes onto the obtained MIP microspheres was confirmed by FT-IR, SEM, water
      dispersion stability and static contact angle studies, and template binding
      experiments. The introduction of PNIPAAm brushes onto the azo-containing MIP
      microspheres significantly improved their surface hydrophilicity and imparted
      thermoresponsive properties to them, leading to their pure water-compatible and
      thermoresponsive template binding properties. In addition, the binding affinity
      of the imprinted sites in the grafted azo-containing MIP microspheres was found
      to be photoresponsive toward the template in pure water, and this photoregulation
      process proved to be highly repeatable under photoswitching conditions.

PMID- 22639882
TI  - The dreaded MDT- " Multidisciplinary team meeting ".

PMID- 22639884
TI  - Delaying emergency treatment for patients with cerebral abscesses and brain
      tumours: a consequence of the neuroscience MDT?

PMID- 22639885
TI  - Large protruding bladder stone.
AB  - We present a unique case of a large urinary bladder stone protruding through the
      external urethral meatus in a 77-year-old woman, which was causing acute urinary
      retention, complicated by bilateral hydronephrosis, and was removed under topical
      anesthesia in the emergency department. Epidemiology, etiology, clinical
      presentation and management of urinary bladder stones are briefly discussed.

PMID- 22639886
TI  - A novel method for measuring catheter lock spillage: an in vitro study.
AB  - Catheters are widely used for blood purification, parenteral nutrition, and for
      the infusion of drugs. Previous work on catheter lock spillage has focused on the
      theory and in vitro demonstration of catheter lock spillage caused by the laminar
      flow profile and by fluid exchange caused by density differences. This work
      describes an in vitro test with a method that potentially allows measurement of
      catheter lock spillage in vivo without sampling. The method is based on the
      change of the electrical resistance of the catheter when the lock solution is
      injected. This method was tested in vitro with human blood at 36 degrees C using
      46.7% trisodium citrate as catheter lock solution. The catheter tip was placed in
      a beaker filled with whole blood. A stainless steel rod in the beaker served as
      one electrode and an Arrow-Johans ECG adapter, which was placed on the distal end
      of the catheter, served as a second electrode. Conductivity was measured with a
      5V (rms) 310 Hz sinus voltage and a 10 kOhm resistor in series to the catheter.
      The driving voltage and the voltage drop at the catheter was continuously
      measured with a program written under LabView (National Instruments), and the
      results were converted into mean trisodium citrate concentrations. Within 20 min,
      the mean trisodium citrate concentration in the catheter decreased to less than
      5%. Unlike the previous methods used for catheter lock spillage measurement, this
      principle can be employed to measure the time course of catheter lock spillage in
      vivo.

PMID- 22639887
TI  - Modeling holo-ACP:DH and holo-ACP:KR complexes of modular polyketide synthases: a
      docking and molecular dynamics study.
AB  - BACKGROUND: Modular polyketide synthases are multifunctional megasynthases which
      biosynthesize a variety of secondary metabolites using various combinations of
      dehydratase (DH), ketoreductase (KR) and enoyl-reductase (ER) domains. During the
      catalysis of various reductive steps these domains act on a substrate moiety
      which is covalently attached to the phosphopantetheine (P-pant) group of the holo
      Acyl Carrier Protein (holo-ACP) domain, thus necessitating the formation of holo
      ACP:DH and holo-ACP:KR complexes. Even though three dimensional structures are
      available for DH, KR and ACP domains, no structures are available for DH or KR
      domains in complex with ACP or substrate moieties. Since Ser of holo-ACP is
      covalently attached to a large phosphopantetheine group, obtaining complexes
      involving holo-ACP by standard protein-protein docking has been a difficult task.
      RESULTS: We have modeled the holo-ACP:DH and holo-ACP:KR complexes for
      identifying specific residues on DH and KR domains which are involved in
      interaction with ACP, phosphopantetheine and substrate moiety. A novel
      combination of protein-protein and protein-ligand docking has been used to first
      model complexes involving apo-ACP and then dock the phosphopantetheine and
      substrate moieties using covalent connectivity between ACP, phosphopantetheine
      and substrate moiety as constraints. The holo-ACP:DH and holo-ACP:KR complexes
      obtained from docking have been further refined by restraint free explicit
      solvent MD simulations to incorporate effects of ligand and receptor
      flexibilities. The results from 50 ns MD simulations reveal that substrate enters
      into a deep tunnel in DH domain while in case of KR domain the substrate binds a
      shallow surface exposed cavity. Interestingly, in case of DH domain the predicted
      binding site overlapped with the binding site in the inhibitor bound crystal
      structure of FabZ, the DH domain from E.Coli FAS. In case of KR domain, the
      substrate binding site identified by our simulations was in proximity of the
      known stereo-specificity determining residues. CONCLUSIONS: We have modeled the
      holo-ACP:DH and holo-ACP:KR complexes and identified the specific residues on DH
      and KR domains which are involved in interaction with ACP, phosphopantetheine and
      substrate moiety. Analysis of the conservation profile of binding pocket residues
      in homologous sequences of DH and KR domains indicated that, these results can
      also be extrapolated to reductive domains of other modular PKS clusters.

PMID- 22639888
TI  - Risk of second breast cancer in female Hodgkin's lymphoma survivors: a meta
      analysis.
AB  - BACKGROUND: Women treated for Hodgkin's lymphoma (HL) have an elevated risk of
      developing second breast cancer (SBC) compared with the general population. We
      planned this meta-analysis to quantify the long-term risk of SBC and analyze the
      contributing risk factors among HL survivors. METHODS: According to predefined
      selection criteria, literature search identified 34 studies that were included in
      the analyses. RESULTS: After eliminating overlapping or duplicate data, 957
      incidences of SBC were encountered in 24,505 females with HL over a median follow
      up of 14.9 years. The medians: age at the diagnosis of HL, age at diagnosis of
      SBC, and latency since HL treatment to the development of SBC were 23.7, 35.0,
      and 17.7 years, respectively. The pooled relative risk (RR) of SBC was 8.23 (95%
      CI, 5.43-12.47, I2 = 96%), with a median absolute excess rate of 22.9 per 10,000
      person-years. The RR was found inversely related to age at diagnosis of HL with
      the highest rate (68.7; [95%CI, 28.08-168.11], I2 = 79%), occurred in young
      patients (<= 15 years old), where the RR in older women (>= 40 years old) was not
      significant (0.55; [95% CI, 0.09-3.52]). Analysis of RR by 5-year increments
      since the treatment of HL showed that the risk was highest after 15-19 years of
      latency (13.87; [95% CI, 7.91-24.30], I2 = 89%). Analysis of the effect of
      treatment modalities showed that the RR rates were (4.70; [95% CI, 3.28-6.75], I2
      = 74%), (5.65; [95%CI, 2.94-10.88], I2 = 91%), and (1.19; [95% CI, 0.50-2.82], I2
      = 65%), for radiotherapy (RT) only, combined RT and chemotherapy (CT), and CT
      only, respectively. To investigate the demonstrated heterogeneity, meta
      regression analysis was performed when feasible. In most such analyses, the
      natural logarithm of RR was inversely associated with age at HL diagnosis.
      CONCLUSIONS: We conclude that, the current meta-analysis provided the most recent
      comprehensive estimate of the risk of SBC in a broad-range of HL survivors.
      Younger age at diagnosis proved to be a dominant risk factor. The obtained
      results would serve providing breast cancer screening recommendations for HL
      survivors.

PMID- 22639889
TI  - Potential role of alpha-synuclein in neurodegeneration: studies in a rat animal
      model.
AB  - Neuronal protein alpha-synuclein (alpha-syn) is an essential player in the
      development of neurodegenerative diseases called synucleinopathies. A spontaneous
      autosomal recessive rat model for neurodegeneration was developed in our
      laboratory. These rats demonstrate progressive increases in alpha-syn in the
      brain mesencephalon followed by loss of dopaminergic terminals in the basal
      ganglia (BG) and motor impairments. The severity of pathology is directly related
      to the overexpression of alpha-syn and parallel decrease in dopamine (DA) level
      in the striatum (ST) of affected rats. The neurodegeneration in this model is
      characterized by the presence of perikarya and neurites Lewis bodies (LB) and
      diffuse marked accumulation of perikaryal alpha-syn in the substantia nigra (SN),
      brain stem (BS), and striatum (ST) along with neuronal loss. Light and
      ultrastructural analyses revealed that the process of neuronal degeneration is a
      'dying back' type. The disease process is accompanied by gliosis and release of
      inflammatory cytokines. This neurodegeneration is a multisystemic disease and
      implicate alpha-syn as a major factor in the pathogenesis of this inherited
      autosomal recessive animal model. Decrease dopamine (DA) and overexpression of
      alpha-syn in the brain mesencephalon may provide a naturally occurring animal
      model for Parkinson's disease (PD) and other synucleinopathies that reproduces
      significant pathological, neurochemical, and behavioral features of the human
      disease.

PMID- 22639893
TI  - Stratum oriens stimulation-evoked modulation of hippocampal long-term
      potentiation involves the activation of muscarinic acetylcholine receptors and
      the inhibition of Kv7/M potassium ion channels.
AB  - Acetylcholine is considered to be an endogenous modulator of hippocampal
      neurotransmission and synaptic plasticity. The activation of muscarinic
      acetylcholine receptors (mAChRs) reportedly enhances hippocampal synaptic
      plasticity, which plays an important role in memory function; however, the
      mechanism by which it enhances synaptic plasticity remains unclear. Here, we
      examined the involvement of the inhibition of Kv7/M K(+)  channels, which are
      targets of mAChR modulation, during mAChR activation-induced enhancement of long
      term potentiation (LTP) at rat hippocampal Schaffer collateral (SC)-CA1 synapses.
      When an electrical stimulus was applied to the stratum oriens before tetanic
      stimulation of the SCs, the magnitude of the induced SC-CA1 synapse LTP was
      enhanced as compared with that induced without stratum oriens stimulation. In the
      presence of the mAChR antagonist atropine, tetanic stimulation induced stable
      LTP, but the stratum oriens stimulation-evoked enhancement of LTP was abolished.
      The additional application of XE991, a selective blocker of Kv7/M K(+)  channels,
      rescued the atropine-induced inhibition of LTP enhancement. The phospholipase C
      (PLC) inhibitor U-73122 inhibited the stratum oriens stimulation-evoked
      enhancement of LTP. Application of the T/R-type voltage-dependent Ca(2+) channel
      (VDCC) blocker Ni(2+) abolished the stratum oriens stimulation-evoked enhancement
      of LTP. In addition, tetanic stimulation with preceding stratum oriens
      stimulation was able to induce LTP during N-methyl-d-aspartate receptor blockade.
      We therefore propose that stratum oriens stimulation inhibits Kv7/M K(+) 
      channels through mAChR activation-induced PLC activation, which leads to VDCC
      activation, and hence causes sufficient Ca(2+)  influx to enhance LTP.

PMID- 22639890
TI  - The balance between two isoforms of LEF-1 regulates colon carcinoma growth.
AB  - BACKGROUND: Colon cancer is one of the most aggressive human malignancies, with a
      very poor prognosis. Although it has been suggested that different isoforms of
      the lymphoid enhancer factor (LEF-1) have opposing biological activities, the
      biological outcome of aberrant LEF-1 activation in colon cancer is still unclear.
      The aim of this study was to evaluate the effect of the different LEF-1
      phenotypes on the growth of colon carcinoma cell lines. A deeper understanding of
      these processes might improve the targeted therapies for colon cancer by
      regulating the expression of LEF-1. METHODS: The role of different isoforms of
      LEF-1 on the growth of human colon carcinoma cell lines (SW480 and HT-29) was
      studied using various in vitro and in vivo assays. In vitro proliferation,
      migration, adhesion and apoptosis of the cells stably transfected of different
      isoforms of LEF-1 were monitored by MTT assay, carboxyfluorescein diacetate
      succinimidyl ester staining, annexin V staining, ECM adhesion assay and transwell
      assay, respectively. In nude mice, the formation of neovasculature in the tumors
      formed by our constructed cells was measured by immunohistochemistry. All the
      data were analyzed using a t test, and data were treated as significant when p <
      0.05. RESULTS: Overexpression of truncated LEF-1 (LEF-1-DeltaL) in the colon cell
      lines, SW480 and HT29, inhibited their growth significantly in vitro and in vivo,
      but the full-length LEF-1 (LEF-1-FL) promoted the proliferation of HT29.
      Inactivation of Wnt signaling by LEF-1-DeltaL reduced the expression of CXCR4 in
      colon cell lines, which may lead to a decrease in activities such as migration,
      adhesion and survival. In nude mice, the formation of neovasculature as well as
      an increase in tumor volume were inhibited by the short isoform of LEF-1. LEF-1
      FL, however, caused an increase in all these parameters compared with controls.
      CONCLUSIONS: These findings suggest that LEF-1 might play an important role in
      colon carcinogenesis by acting as a regulator. Enhanced expression of LEF-1-FL,
      which occurs frequently in colon cancer, may be a new target for clinical
      therapy.

PMID- 22639894
TI  - The safety and efficacy of red cell transfusions in neonates: a systematic review
      of randomized controlled trials.
AB  - Premature neonates commonly receive red blood cell (RBC) transfusions. This study
      systematically identified and appraised randomized controlled trials (RCTs) where
      the intervention was 'transfusion of red blood cells' from searches of multiple
      databases. Primary review outcomes were mortality, neurodevelopmental and
      respiratory endpoints. Two reviewers extracted data and assigned overall quality.
      Twenty-seven RCTs were identified and grouped into four predefined categories:
      trials comparing RBC transfusion versus no transfusion/placebo (n = 3); different
      thresholds for transfusion (n = 6); differing doses or administration schedule (n
      = 4), or different types or products of RBC (n = 14). In the threshold group of
      trials, enrolling 679 neonates, no significant differences in mortality (relative
      risk 1.22, 95% confidence interval 0.84-1.75) or chronic lung disease were found.
      Only two trials assessed neurodevelopment outcomes, both within the threshold
      group, but with differing results. The largest subgroup of RCTs by number
      evaluated different media for storage of red cells (n = 7), enrolling 221
      neonates. The methodological quality of many RCTs was poor. The design of future
      RCTs can be informed by the lessons from this review. Many trials failed to
      report on outcomes that would be considered of primary importance to clinicians.
      Consistent reporting of adverse events is required, and endpoints need to include
      neurodevelopmental outcomes.

PMID- 22639895
TI  - Real time three-dimensional echocardiography and endovascular stenting.
AB  - A 52-year-old male with HIV and chronic renal failure presented with 2-day
      history of fever and chills. He had recent superior vena cava (SVC) stent
      placement for SVC stenosis following multiple dialysis-catheter insertions.
      Patient's blood cultures grew methicillin-resistant staphylococcus aureus. Two
      dimensional (2D) echocardiography showed no vegetations. With high clinical
      suspicion, 2D transesophageal echocardiogram (TEE) was obtained and confirmed no
      endocarditis and patent stent at SVC right atrial junction; however, entire stent
      was not visualized. Simultaneous three-dimensional TEE provided superior views of
      SVC stent in cross-sectional and longitudinal planes, clearly demonstrating
      patent stent without vegetations, stenosis, migration, or thrombosis.

PMID- 22639896
TI  - A combination of aortic arch debranching and off-pump coronary artery bypass.
AB  - The prevalence of coronary artery disease in patients with aortic aneurysm is
      high. As an antecedent percutaneous coronary intervention with antiplatelet
      therapy may cause a rupture of aortic aneurysm, concomitant treatment for aortic
      arch aneurysm and coronary artery disease is recommended. We report a technique
      of a combined procedure of antegrade endovascular repair with aortic arch
      debranching and off-pump coronary artery bypass grafting.

PMID- 22639897
TI  - The ACTN3 R577X polymorphism is associated with inflammatory myopathies in a
      Mexican population.
AB  - BACKGROUND: The ACTN3 gene encodes the fast muscle protein alpha-actinin-3. The
      ACTN3 R577X polymorphism is a premature stop codon and results in absence of
      alpha-actinin-3 in 577XX homozygotes. The aim of this study was to determine the
      ACTN3 genotype in idiopathic inflammatory myopathies (IIMs). METHODS: We
      performed ACTN3 genotyping on 27 patients with dermatomyositis (DM), 10 with
      polymyositis (PM), and 85 healthy subjects. Muscle enzyme levels of creatine
      phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate aminotransferase
      (AST), and alanine aminotransferase (ALT) were recorded at the time of diagnosis
      and recruitment. Genotyping was performed by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and the allele frequency was
      analysed. RESULTS: A total of 36% of healthy subjects had the ACTN3 577XX
      polymorphism (alpha-actinin-3 deficiency), 18% had the 577RR (homozygous wild
      type) genotype, and 46% 577RX (heterozygous). In DM/PM, 70% had the ACTN3 577XX
      polymorphism, 6% RR, and 24% RX [odds ratio (OR) 4.12, 95% confidence interval
      (CI) 1.67-10.33, p < 0.001]. In healthy subjects, the R allele was present in 41%
      and the X allele in 59% compared to 18% and 82%, respectively, in the IIM group
      (OR 3.21, 95% CI 1.57-6.66, p < 0.001). Thus, the ACTN3 577X allele seemed to
      increase the risk of developing IIM, and DM in particular, although this was not
      related to severity of expression of the phenotype. CONCLUSIONS: The ACTN3 577X
      allele appeared to increase the risk of developing IIM; 70% of IIM patients were
      deficient in alpha-actinin-3. By contrast, ACTN3 577XX patients seemed to have
      less severe disease as reflected in lower muscle enzyme levels.

PMID- 22639898
TI  - Mitochondrial function in human brains is affected by pre- and post mortem
      factors.
AB  - AIM: Mitochondrial function and the ensuing ATP synthesis are central to the
      functioning of the brain and contribute to neuronal physiology. Most studies on
      neurodegenerative diseases have highlighted that mitochondrial dysfunction is an
      important event contributing to pathology. However, studies on the human brain
      mitochondria in various neurodegenerative disorders heavily rely on post mortem
      samples. As post mortem tissues are influenced by pre- and post mortem factors,
      we investigated the effect of these variables on mitochondrial function. METHODS:
      We examined whether the mitochondrial function (represented by mitochondrial
      enzymes and antioxidant activities) in post mortem human brains (n=45) was
      affected by increased storage time (11.8-104.1 months), age of the donor (2 days
      to 80 years), post mortem interval (2.5-26 h), gender difference and agonal state
      [based on Glasgow Coma Scale: range=3-15] in the frontal cortex, as a prototype.
      RESULTS: We observed that the activities of citrate synthase, succinate
      dehydrogenase and mitochondrial reductase (MTT) were significantly affected only
      by gender difference (citrate synthase: P=0.005; succinate dehydrogenase: P=0.01;
      mitochondrial reductase: P=0.006), being higher in females, but not by any other
      factor. Mitochondrial complex I activity was significantly inhibited by
      increasing age (r=-0.40; P=0.05). On the other hand, the mitochondrial
      antioxidant enzyme glutathione reductase decreased with severe agonal state
      (P=0.003), while the activity of glutathione-S-transferase declined with
      increased storage time (P=0.005) and severe agonal state (P=0.02). CONCLUSION:
      Our data highlight the influence of pre- and post mortem factors on preservation
      of mitochondrial function with implications for studies on brain pathology
      employing stored human samples.

PMID- 22639899
TI  - The UK Clinical Aptitude Test: is it a fair test for selecting medical students?
AB  - BACKGROUND: The United Kingdom Clinical Aptitude Test (UKCAT) is designed to
      increase diversity and fairness in selection to study medicine. AIM: The aim of
      this study is to determine if differences in: access to support and advice, in
      modes of preparation, type of school/college attended, level of achievement in
      mathematics, gender and age influence candidate performance in the UKCAT and
      thereby unfairly advantage some candidates over others. METHODS: Confidential,
      self-completed, on-line questionnaire of applicants to study on an undergraduate
      medical degree course who had taken the UKCAT in 2010. RESULTS: Differentials in
      access to support and advice, in modes of preparation, type of school/college
      attended, in level of achievement in mathematics, gender and age were found to be
      associated with candidate performance in the UKCAT. CONCLUSION: The findings
      imply that the UKCAT may disadvantage some candidate groups. This inequity would
      likely be improved if tutors and career advisors in schools and colleges were
      more informed about the UKCAT and able to offer appropriate advice on preparation
      for the test.

PMID- 22639900
TI  - Self-assembly and emulsification of poly{[styrene-alt-maleic acid]-co-[styrene
      alt-(N-3,4-dihydroxyphenylethyl-maleamic acid)]}.
AB  - Self-assembled polymeric micelles can be used as efficient particulate
      emulsifiers. To explore the relationship between the structure and the oil-water
      interfacial behavior of the micelle emulsifiers, a new type of amphiphilic random
      copolymer, poly{(styrene-alt-maleic acid)-co-[styrene-alt-(N-3,4
      dihydroxyphenylethyl-maleamic acid)]} (SMA-Dopa), was synthesized, self-assembled
      into micelles, and used as emulsifiers. SMA-Dopa was synthesized via an
      aminolysis reaction between dopamine and commercial alternating copolymer
      poly(styrene-alt-maleic anhydride) (SMA). Dopamine moiety facilitated the self
      assembly of the SMA-Dopa in selective-solvent into stable micelles, and increased
      the adsorption of the SMA-Dopa at the oil-water interface. Additionally, the
      structural transition of the self-assembled SMA-Dopa52 micelles in response to pH
      and salinity changes were confirmed by means of TEM, AFM, DLS, aqueous
      electrophoresis techniques, potentiometric titration, and pyrene fluorescence
      probe methods. Micelles shrunk with increasing salinity, and flocculation of the
      shrunken primary micelles occurred at salt concentration exceeding 0.1 M. The
      micelles swelled with increasing pH, and the disassociation of the SMA-Dopa52
      micelles occurred at pH above approximately 6.5. The structure of the micelles
      plays a crucial role in the oil-water interfacial performance. Micelles with
      various structures were used as emulsifiers to adsorb at the styrene-water and
      toluene-water interfaces. The emulsifying characteristics demonstrated that self
      assembled SMA-Dopa52 micelles with moderately swollen structure (at 2 < pH < 6)
      combine the advantages of the solid particulate emulsifiers and polymeric
      surfactants, possessing excellent emulsifying efficiency and good emulsion
      stability. Moreover, the emulsifying performance of the SMA-Dopa52 micelles could
      be enhanced by the addition of salt.

PMID- 22639901
TI  - The power of the past: nostalgia as a meaning-making resource.
AB  - In three experiments we tested whether nostalgia bolsters meaning in life
      relative to two other modes of autobiographical thought: imagining a desired
      future experience and recalling a positive past experience. In Experiment 1
      participants thought about a nostalgic or desired future experience and then
      completed a presence of meaning scale. Thinking about a nostalgic (compared to
      desired future) experience increased perceived presence of meaning. In Experiment
      2 we examined whether nostalgia can additionally reduce the search for meaning.
      Participants thought about a nostalgic, desired future or recent positive
      experience, and then completed a search for meaning scale. Nostalgia, relative to
      both comparison conditions, decreased the search for meaning. Finally we tested
      whether, by virtue of its capacity to increase meaning, nostalgia can mitigate
      threats to meaning. In Experiment 3 participants were exposed to either absurd or
      representational art, under the guise that they would later have to interpret its
      meaning, and then thought about either a nostalgic or a recent positive
      experience. Meaning was subsequently measured. The absurd art interpretation
      condition decreased the perceived presence of meaning but nostalgic reflection
      attenuated this effect.

PMID- 22639902
TI  - Value of serum urocortin concentration in the prediction of preterm birth.
AB  - AIM: Preterm delivery is a serious problem during pregnancy with remarkable
      neonatal adverse effects. Prediction of preterm delivery in women with preterm
      uterine contractions or signs of preterm labor is critical because if these women
      are identified they can be referred to tertiary centers. The present study aimed
      to evaluate the value of maternal serum urocortin concentration for predicting
      preterm delivery in women with signs of spontaneous preterm labor. MATERIAL AND
      METHODS:   A cohort study was conducted on pregnant women at a gestational age of
      28-36 weeks who were admitted to the labor ward with spontaneous preterm labor. A
      blood sample was obtained from all participants to measure serum urocortin. The
      women were monitored up to delivery and serum urocortin was compared between
      women with preterm delivery and those who delivered at term (37 weeks of
      gestation). Receiver Operating Characteristic (ROC) curve analysis was used to
      determine sensitivity and specificity if applicable. RESULTS:   One hundred and
      sixty pregnant women finished the study. One hundred and forty-eight (92.5%) of
      the women delivered preterm. Mean serum urocortin in the preterm delivery group
      was higher than in the term group, but without statistical significant difference
      (392.6 +/- 29.23 vs 113.2 +/- 11.0. pg/mL, respectively, P = 0.252). Area under
      the ROC curve was 0.6, which shows that this test is not appropriate for
      predicting preterm delivery in women with preterm labor. CONCLUSION:   Serum
      urocortin could not predict women who delivered preterm among women with signs of
      preterm labor.

PMID- 22639903
TI  - Conference overview: Cancer Immunotherapy and Immunomonitoring (CITIM): moving
      forward.
AB  - The immune system is a critical element involved in the control of tumor
      development and progression. While professionals have learned how to manipulate
      the immune system to generate tumor-specific immune responses, cancer
      immunotherapy has not yet delivered substantial clinical benefits. It has become
      increasingly clear that tumor-induced abnormalities in the immune system not only
      hamper tumor immunosurveillance, but also limit the efficacy of cancer
      immunotherapy. Meanwhile, the results of recent studies allow the belief that one
      is on the edge of a real breakthrough in this promising direction in cancer
      therapy. The 2(nd) International Conference 'Cancer Immunotherapy and
      Immunomonitoring (CITIM)' was the second meeting in Eastern Europe to
      specifically focus on the issue of immune regulation in the tumor environment,
      cancer immunotherapy, and immunomonitoring of immunotherapeutic clinical trials.
      This CITIM Conference held in Budapest, Hungary, was comprised from 12 plenary
      sessions, Best Abstract Award session, Poster session, and four Keynote lectures.
      Outstanding presentations and numerous productive discussions summarized the
      current place of the field and opened new directions for improving monitoring and
      therapy for patients with cancer.

PMID- 22639904
TI  - Acute pain management and assessment: are guidelines being implemented in
      developing countries (Lebanon).
AB  - RATIONALE: Pain assessment and treatment is influenced by subjective perception
      of pain. Despite the international efforts to implement guidelines and protocols
      for pain management, pain continues to be regarded as a complication rather than
      a primary problem. The literature pertaining to the adequacy of pain management
      in the Middle East is frail. This study focuses on revealing the implemented
      practices of initial pain assessment, follow-up and re-evaluation of pain
      treatment in Lebanese hospitals. AIM AND OBJECTIVES: The objective of this study
      is to evaluate the presence and effectiveness of acute pain management and its
      impact on the quality of life in hospitals throughout Lebanon, in both cancer and
      non-cancer populations. METHODS: A Lebanese multi-centre, prospective, chart
      review study was conducted over a period of 3 months. Data on demographics, pain
      medication, dose, route, duration and adjunct pain management were collected.
      Appropriateness of pain management was determined as per World Health
      Organization guidelines. Institutional Review Board approvals were obtained from
      each hospital. RESULTS: Results from 582 participants revealed that 50% of
      initial pain assessment intensity scores were based on the assumptions of health
      care professionals. Furthermore, as pain severity scores increased, the adequacy
      of pain management decreased. Only 22% of the patients had a daily follow-up, and
      the majority of those continued to receive inappropriate therapy. CONCLUSION:
      This study reflects the lack of a well-structured system for pain management in
      Lebanese hospitals. It underlines the need for pain research in the region. It
      also highlights the need for implementing the recommendations discussed to
      minimize risk and optimize pain management.

PMID- 22639905
TI  - Identification of cis-elements conferring high levels of gene expression in non
      green plastids.
AB  - Although our knowledge about the mechanisms of gene expression in chloroplasts
      has increased substantially over the past decades, next to nothing is known about
      the signals and factors that govern expression of the plastid genome in non-green
      tissues. Here we report the development of a quantitative method suitable for
      determining the activity of cis-acting elements for gene expression in non-green
      plastids. The in vivo assay is based on stable transformation of the plastid
      genome and the discovery that root length upon seedling growth in the presence of
      the plastid translational inhibitor kanamycin is directly proportional to the
      expression strength of the resistance gene nptII in transgenic tobacco plastids.
      By testing various combinations of promoters and translation initiation signals,
      we have used this experimental system to identify cis-elements that are highly
      active in non-green plastids. Surprisingly, heterologous expression elements from
      maize plastids were significantly more efficient in conferring high expression
      levels in root plastids than homologous expression elements from tobacco. Our
      work has established a quantitative method for characterization of gene
      expression in non-green plastid types, and has led to identification of cis
      elements for efficient plastid transgene expression in non-green tissues, which
      are valuable tools for future transplastomic studies in basic and applied
      research.

PMID- 22639906
TI  - Water-sediment niche differentiation in ancient marine lineages of
      Exiguobacterium endemic to the Cuatro Cienegas Basin.
AB  - The evolutionary history and ecological differentiation of the genus
      Exiguobacterium was characterized within natural communities from the Cuatro
      Cienegas Basin, Mexico. Exiguobacterium comprises both halophilic and
      alkaliphilic bacteria that are abundant among the aquatic systems of the Cuatro
      Cienegas Basin. We obtained complete sequences of the 16srRNA gene and partial
      sequences of four housekeeping genes (citC, rpoB, recA and hsp70) in 183
      Exiguobacterium isolates retrieved from distinct aquatic systems. We defined
      three main phylogroups that are closely related to marine and thermophilic
      species of the genus. These phylogroups were neither specific to a given aquatic
      system nor to a particular salinity. Phylogenetic reconstruction indicated the
      presence of several small clusters within the phylogroups. These clusters
      consisted of isolates predominantly retrieved from sediment or water. Unifrac and
      AdaptML analyses confirmed this observation, pointing towards a clear pattern of
      differentiation linked to either sediment or water habitats. Our results are in
      line with the concept that niche differentiation is one of the main factors
      shaping prokaryotic populations and leading to evolutionary divergence.

PMID- 22639907
TI  - Verrucous carcinoma in epidermolysis bullosa simplex is possibly associated with
      a novel mutation in the keratin 5 gene.
AB  - Epidermolysis bullosa simplex (EBS) is mainly caused by mutations in the KRT5 and
      KRT14 genes. Squamous cell carcinoma (SCC) represents the second most frequent
      skin neoplasia with complex aetiology. The molecular events disrupting the
      orchestrated interplay between the cytoskeleton, cell adhesion molecules and
      signalling proteins are ill understood in SCC. We describe the molecular
      background and the unusual course of the disease in a patient with EBS Dowling
      Meara, severe keratoderma and a massive verrucous carcinoma. Skin and tumour
      samples from the patient were analysed using light microscopy,
      immunohistochemistry and immunofluorescence mapping. Mutation analysis of the
      KRT5 and KRT14 genes identified the novel KRT5 mutation p.E477D. Invasive tumour
      areas were characterized by downregulation of keratins 5 and 14, reduced and
      irregular desmocollin-2 expression and increased expression of keratins 6, 16 and
      17. Levels of Ki-67 were increased and levels of E-cadherin strongly reduced in
      the tumour tissue. In this case a novel KRT5 mutation led to increased fragility
      of keratinocytes. Desmosome and adherens junctions were destabilized, which may
      trigger keratinocyte-mediated inflammation, possibly via p120-catenin-dependent
      signalling, suggesting a link between a keratin mutation and SCC, which adds
      weight to the hypothesis that disturbance of the cytoskeleton represents a major
      cause in the appearance of the malignant phenotype. Some individuals with EBS may
      be at risk of developing secondary SCC.

PMID- 22639908
TI  - Constitutively active c-Met kinase in PC-3 cells is autocrine-independent and can
      be blocked by the Met kinase inhibitor BMS-777607.
AB  - BACKGROUND: The c-Met receptor tyrosine kinase is aberrantly activated in many
      solid tumors. In a prior study we showed that prostate cancer PC-3 cells exhibit
      constitutively activated c-Met without exogenous hepatocyte growth factor (HGF);
      however whether this characteristic is due to an endogenous HGF/c-Met autocrine
      loop remains controversial. In the current study we examined the response of PC-3
      cells to an anti-HGF neutralizing antibody or a small molecule Met kinase
      inhibitor (BMS-777607). METHODS: Cell scattering was tested by monitoring cell
      morphology after HGF stimulation. Cell migration was examined by both "wound
      healing" and transwell assasy and invasion was detected by Matrigel-coated
      transwell assay. Proliferation, survival and anoikis were determined by MTT,
      colony formation and trypan blue exclusion assay, respectively. Gene and protein
      expression were assessed by real-time PCR and Western blot, respectively.
      RESULTS: Although HGF mRNA could be detected in PC-3 cells, the molecular weight
      of secreted "HGF" protein was inconsistent with the functional recombinant HGF.
      Furthermore, conditioned medium from PC-3 cell cultures was ineffective at
      triggering either motogenic behavior or c-Met signaling in DU145, another
      prostate cancer cell line expressing c-Met but lacking basal c-Met activation. PC
      3 cells also were not responsive to the anti-HGF neutralizing antibody in
      experiments assessing proliferation, migration, or c-Met signaling. BMS-777607
      treatment with micromolar doses nonetheless led to significant inhibition of
      multiple PC-3 cell functions including proliferation, clonogenicity, migration
      and invasion. At the molecular level, BMS-777607 suppressed autophosphorylated c
      Met and downstream c-Src and Akt pathways. CONCLUSIONS: These results suggest
      that the constitutive c-Met activation in PC-3 is independent of autocrine
      stimulation. Because PC-3 cells were responsive to BMS-777607 but not the anti
      HGF antibody, the findings also indicate that under circumstances where c-Met is
      constitutively hyperactive in the absence of functional HGF, targeting the c-Met
      receptor remains a viable therapeutic option to impede cancer progression.

PMID- 22639909
TI  - Atrophic congenital melanocytic nevus mimicking rapidly involuting congenital
      hemangioma.
AB  - Congenital melanocytic nevi (CMN) are benign skin lesions present in some
      newborns. We describe a newborn boy with a giant CMN on the scalp. It appeared as
      an atrophic patch with a central nodule that was suggestive of a rapidly
      involuting congenital hemangioma or some other vascular tumor. Histopathology
      confirmed the diagnosis of CMN. Magnetic resonance imaging was normal, excluding
      leptomeningeal melanocytosis. We did not find any other cases of CMN with this
      presentation in the literature. 

PMID- 22639911
TI  - Ammonia-induced deficit in corticostriatal long-term depression and its
      amelioration by zaprinast.
AB  - Hyperammonemia is a major pathophysiological factor in encephalopathies
      associated with acute and chronic liver failure. On mouse brain slice
      preparations, we analyzed the effects of ammonia on the characteristics of
      corticostriatal long-term depression (LTD) induced by electrical stimulation of
      cortical input or pharmacological activation of metabotropic glutamate receptors.
      Long exposure of neostriatal slices to ammonium chloride impaired the induction
      and/or expression of all studied forms of LTD. This impairment was reversed by
      the phosphodiesterase inhibitor zaprinast implying lowered cGMP signaling in LTD
      suppression. Polyphenols from green tea rescued short-term corticostriatal
      plasticity, but failed to prevent the ammonia-induced deficit of LTD. Zaprinast
      counteracts the ammonia-induced impairment of long-term corticostriatal
      plasticity and may thus improve fine motor skills and procedural learning in
      hepatic encephalopathy.

PMID- 22639910
TI  - Severe tooth wear in Prader-Willi syndrome. A case-control study.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is a rare complex multsystemic genetic
      disorder characterized by severe neonatal hypotonia, endocrine disturbances,
      hyperphagia and obesity, mild mental retardation, learning disabilities, facial
      dysmorphology and oral abnormalities. The purpose of the present study was to
      explore the prevalence of tooth wear and possible risk factors in individuals
      with Prader-Willi syndrome. METHODS: Forty-nine individuals (6-40 years) with PWS
      and an age- and sex-matched control group were included. Tooth wear was evaluated
      from dental casts and intraoral photographs and rated by four examiners using the
      Visual Erosion Dental Examination (VEDE) scoring system and the individual tooth
      wear index IA. In accordance with the VEDE scoring system, tooth wear was also
      evaluated clinically. Whole saliva was collected. RESULTS: Mean VEDE score was
      1.70 +/- 1.44 in the PWS group and 0.46 +/- 0.36 in the control group (p <
      0.001). Median IA was 7.50 (2.60-30.70) in the PWS group and 2.60 (0.90-4.70)
      among controls (p < 0.001). In the PWS group tooth wear correlated significantly
      with age (VEDE; r = 0.79, p < 0.001, IA; r = 0.82, p < 0.001) and saliva
      secretion (VEDE; r = 0.46, p = 0.001, IA; r = 0.43, p = 0.002). Tooth grinding
      was also associated with tooth wear in the PWS group, as indicated by the mean
      VEDE 2.67 +/- 1.62 in grinders and 1.14 +/- 0.97 in non-grinders (p = 0.001) and
      median IA values 25.70 (5.48-68.55) in grinders and 5.70 (1.60-9.10) in non
      grinders (p = 0.003). Multivariate linear regression analysis was performed with
      tooth wear as the dependent variable and PWS (yes/no), age, tooth grinding and
      saliva secretion as independent variables. PWS (yes/no), age and tooth grinding
      retained a significant association with tooth wear, VEDE (p < 0.001) and log IA
      (p < 0.001). The only factor significantly associated with tooth wear in the
      control group was age. CONCLUSIONS: Our study provides evidence that tooth wear,
      in terms of both erosion and attrition, is a severe problem in Prader-Willi
      syndrome. There is therefore considerable need for prosthodontic rehabilitation
      in young adults with PWS.

PMID- 22639912
TI  - Prevalence of the bacterium Coxiella burnetii in wild rodents from a Canadian
      natural environment park.
AB  - Zoonotic diseases impact both wild and domestic animal populations and can be
      transmitted to humans through close contact with animal species. Reservoir
      species acting as vectors are major traffickers of disease. Rodents contribute to
      the transmission of Coxiella burnetii although little is known about its
      prevalence in wild animal populations. DNA was extracted from genital swabs
      collected from woodland jumping mice, deer mice, Southern red-backed voles,
      Eastern chipmunks, North American red squirrels, as well as Southern and Northern
      flying squirrels collected from Algonquin Park, Canada. The presence of C.
      burnetii was determined through real-time PCR. All species sampled had some
      prevalence of infection, except Eastern chipmunks, indicating wild rodents in
      Algonquin Park are reservoirs for C. burnetii. Emerging zoonotic diseases are
      linked to increasing globalization. Contact amongst individuals increases as
      crowding, habitat loss and fragmentation increase within wild spaces. Parks often
      act as a last refuge for wildlife but may also be an important transmission zone
      of wildlife disease to humans. Investigations that attempt to discover wild
      reservoir species of zoonotic disease are critically important to understanding
      the risk of pathogen exchange between wild and human populations.

PMID- 22639914
TI  - Strongyloides stercoralis hyperinfection in a patient treated for multiple
      myeloma.

PMID- 22639913
TI  - Palm vitamin E reduces catecholamines, xanthine oxidase activity and gastric
      lesions in rats exposed to water-immersion restraint stress.
AB  - BACKGROUND: This study examined the effects of Palm vitamin E (PVE) and alpha
      tocopherol (alpha-TF) supplementations on adrenalin, noradrenalin, xanthine
      oxidase plus dehydrogenase (XO + XD) activities and gastric lesions in rats
      exposed to water-immersion restraint stress (WIRS). METHODS: Sixty male Sprague
      Dawley rats (200-250 g) were randomly divided into three equal sized groups. The
      control group was given a normal diet, while the treated groups received the same
      diet with oral supplementation of PVE or alpha-TF at 60 mg/kg body weight. After
      the treatment period of 28 days, each group was further subdivided into two
      groups with 10 rats without exposing them to stress and the other 10 rats were
      subjected to WIRS for 3.5 hours. Blood samples were taken to measure the
      adrenalin and noradrenalin levels. The rats were then sacrificed following which
      the stomach was excised and opened along the greater curvature and examined for
      lesions and XO + XD activities. RESULTS: The rats exposed to WIRS had lesions in
      their stomach mucosa. Our findings showed that dietary supplementations of PVE
      and alpha-TF were able to reduce gastric lesions significantly in comparison to
      the stressed control group. WIRS increased plasma adrenalin and noradrenalin
      significantly. PVE and alpha-TF treatments reduced these parameters significantly
      compared to the stressed control. CONCLUSIONS: Supplementations with either PVE
      or alpha-TF reduce the formation of gastric lesions. Their protective effect was
      related to their abilities to inhibit stress induced elevation of adrenalin and
      noradrenalin levels as well as through reduction in xanthine oxidase and
      dehydrogenase activities.

PMID- 22639916
TI  - Layer-by-layer self-assembly under high gravity field.
AB  - In the present article, we have developed a facile and rapid method to fabricate
      a polyelectrolyte multilayer under high gravity field and investigated the
      difference of mass transfer in the diffusing process between LbL self-assembled
      technique under high gravity field (HG-LbL) and dipping assembly. Herein, we have
      employed polyethyleneimine and zinc oxide nanoparticles, which is a well-known UV
      blocking material with typical absorption properties in the range of 300-400 nm,
      as building blocks and applied hydrogen bonding as the driving force to construct
      the multilayer under HG-LbL and dipping assembly. The results show that, compared
      with dipping assembly, HG-LbL can highly improve the utilization and adsorption
      efficiency of building blocks by hastening the diffusing process, and meanwhile
      the resulting multilayer films still achieve comparable quality as those prepared
      from dipping assembly.

PMID- 22639915
TI  - Green tea catechins decrease oxidative stress in surgical menopause-induced
      overactive bladder in a rat model.
AB  - What's known on the subject? and What does the study add? Ovary hormone
      deficiency and the age-related changes in post-menopausal women are subjected to
      a number of urological dysfunctions, including overactive bladder syndrome. Green
      tea is a popular healthy drink worldwide and its extract catechin has strong anti
      inflammatory and antioxidant properties. EGCG, the major type of catechin, is an
      antioxidant polyphenol flavonoid isolated from green tea. EGCG supplement could
      prevent ovariectomy-induced bladder dysfunction in a dose-related manner through
      its anti-oxidant, anti-fibrosis and anti-apoptosis effects. OBJECTIVE: To
      evaluate whether green tea extract, epigallocatechin gallate (EGCG), could
      prevent ovariectomy-induced overactive bladder (OAB) and to investigate its
      antioxidant, anti-apoptotic and anti-fibrosis effects. MATERIALS AND METHODS: In
      all, 48 female Sprague-Dawley rats were divided into four groups. After bilateral
      ovariectomy, the first group served as the ovariectomy control, the second group
      received EGCG 1 uM/kg daily i.p. injection after ovariectomy surgery, and the
      third group received EGCG 10 uM/kg daily i.p. injection. The fourth group was
      taken as the sham without ovariectomy surgery. The rats were killed after 6
      months after ovariectomy surgery. Cystometrograms were performed for the measure
      of bladder overactivity. Terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick-end labelling (TUNEL) assay was used to evaluate apoptotic cells.
      Western immunoblots were performed to determine the expressions of inflammatory
      markers, apoptosis-associated proteins and oxidative stress markers. RESULTS:
      Long-term ovariectomy significantly increased non-voiding contractions and
      decreased bladder compliance. Treatment with EGCG significantly increased bladder
      compliance and diminished non-voiding contractions. Ovariectomy significantly
      increased apoptotic cells and enhanced interstitial fibrosis in bladders. The
      expression of caspase-3 significantly increased, while that of Bcl-2 notably
      decreased after ovariectomy. Inflammatory and fibrosis markers, TGF-beta,
      fibronectin and type I collagen expressions were significantly increased after 6
      months of ovariectomy surgery. Treatment with EGCG significantly decreased TGF
      beta and type I collagen expressions. Oxidative stress markers, nitrotyrosine and
      protein carbonylation levels were significantly increased in the ovariectomy
      group. EGCG could attenuate this oxidative damage in dose-dependent fashion.
      CONCLUSIONS: Ovariectomy increased oxidative damage, enhanced voiding frequency
      and decreased bladder compliance. EGCG could restore ovariectomy-induced bladder
      dysfunction in a dose-dependent fashion through antioxidant, anti-fibrosis and
      anti-apoptosis effects.

PMID- 22639917
TI  - Outcome of Prolift mesh repair in treatment of pelvic organ prolapse and its
      effect on lower urinary tract symptoms: 5-year retrospective case study.
AB  - AIM: To assess the outcome of the Prolift Gynecare (Ethicon, Somerville, NJ, USA)
      mesh repair in the treatment of pelvic organ prolapse. This includes the
      anatomical success, complication rate and effect on associated lower urinary
      tract symptoms. MATERIAL AND METHODS: Retrospective case analysis of the above
      outcomes of 41 Prolift mesh repairs performed on 40 women over a 5-year period by
      a single surgeon in a private hospital in Australia. RESULTS: Successful
      anatomical correction and bulge symptom resolution were observed in 100% (2/2),
      91.6% (11/12) and 100% (27/27) of anterior, posterior and total Prolift,
      respectively. Prolapse in a non-treated compartment occurred in one woman. Two
      patients developed postoperative hematomas requiring surgical evacuation; one of
      whom developed urinary retention for 2 weeks. Preoperative urinary symptoms were
      reported in 35/40 (92%) of women, 8 of whom reported only urge symptoms and
      experienced complete resolution after Prolift. Resolution of stress urinary
      incontinence in women who had urodynamic stress incontinence with and without
      urge symptoms was reported in 60% (12/20) and 20% (1/5), respectively. This
      represented 62.5% (10/16) and 33.3% (3/9) of women who had total Prolift and
      posterior Prolift respectively. Average follow-up periods were 7 and 39 weeks in
      38 and 18 women, respectively. CONCLUSION: This study shows that Prolift
      procedure is safe and effective in women with severe pelvic organ prolapse with
      resolution of most of the bulge and urinary urge symptoms. Total Prolift was
      effective in the treatment of associated mixed urinary incontinence.

PMID- 22639918
TI  - Turning CALM into excitement: AP180 and CALM in endocytosis and disease.
AB  - Dynamic flux of membrane between intracellular compartments is a key feature of
      all eukaryotic cells. Soluble N-ethylmaleimide-sensitive factor attachment
      protein receptors (SNAREs) play a crucial role in membrane dynamics by
      facilitating membrane fusion, for example at synapses where small synaptic
      vesicles (SVs) undergo activity-regulated neuroexocytosis, followed by the
      endocytic re-cycling of SV proteins and lipids. Recent work shows that the
      assembly protein 180 (AP180) N-terminal homology (ANTH) domain containing
      proteins AP180 and clathrin assembly lymphoid myeloid leukaemia (CALM) not only
      regulate the assembly of the endocytic machinery but also act as sorters for a
      subset of SNAREs, the vesicle-associated membrane proteins (VAMPs), most notably
      VAMP/synaptobrevin 2 at synapses. In this review, we summarise the current state
      of knowledge about the roles of AP180 and CALM family members in clathrin
      dependent membrane traffic, the molecular mechanistic basis for their activities
      and their potential involvement in human disease.

PMID- 22639919
TI  - Human antimicrobial peptides LL-37 and human beta-defensin-2 reduce viral
      replication in keratinocytes infected with varicella zoster virus.
AB  - BACKGROUND: There is mounting evidence that antimicrobial peptides have an
      important role in cutaneous defence, but the expression of these antimicrobial
      peptides in atopic eczema (AE) is still unclear. There are several families of
      antimicrobial peptides, including cathelicidins and human beta-defensins.
      Patients with AE are more susceptible to severe cutaneous viral infections,
      including varicella zoster virus (VZV). AIM: To characterize the functional
      activity of the antimicrobial peptides LL-37 (human cathelicidin) and human beta
      defensin (hBD)-2 keratinocytes were infected with VZV, in a skin-infection model.
      METHODS: Flow-cytometry analysis was used to investigate LL-37 expression in
      normal human keratinocytes, and quantitative PCR was used to determine viral
      loads in infected HaCaT keratinocytes and B cells, with and without exogenous LL
      37 and hBD-2. RESULTS: LL-37 expression was present in keratinocytes, and both
      exogenous LL-37 and hBD-2 significantly reduced VZV load in infected
      keratinocytes and B cells. Specific antibodies blocked the antiviral action
      exhibited by these antimicrobial peptides. Pre-incubation of VZV with LL-37, but
      not hBD-2, further reduced VZV load. CONCLUSIONS: Both LL-37 and hBD-2 have an
      antiviral effect on VZV replication in the keratinocyte HaCaT cell line and in B
      cells, but their mechanism of action is different. Evidence of the relationship
      between antimicrobial peptide expression and higher susceptibility to infections
      in AE skin is still emerging. Developing novel antiviral therapies based on
      antimicrobial peptides may provide improved treatment options for patients with
      AE.

PMID- 22639920
TI  - Imagining novel futures: the roles of event plausibility and familiarity.
AB  - The constructive episodic simulation hypothesis suggests that episodic memory
      supports the simulation of future events through extraction and recombination of
      stored information. The current study explicitly investigated the use of past
      episodic thought in the simulation of future scenarios. Participants simulated
      one of three possible scenarios, differing in plausibility and participants'
      prior experience of similar events. Participants recorded related memories and
      whether they were explicitly used during future event simulation. Memories were
      rated for source (self-experienced, other-experienced, or media). Findings
      suggest prior experience and event plausibility did not impact upon ease of
      future event simulation or the extent of memory usage during simulations.
      Differences emerged in the source of information used to assist future event
      simulation. These findings provide support for the hypothesis that episodic
      memories from a variety of sources are recombined when generating future
      simulations of novel events.

PMID- 22639921
TI  - Three-dimensional imaging of pannus overgrowth after mitral valve repair.
AB  - We present the case of a 65-year-old man who was diagnosed with late mitral
      stenosis caused by pannus formation after Duran ring annuloplasty due to
      ischemicmitral regurgitation. Threedimensional echocardiography provided signifi
      cant information regarding the anatomy of the valve and the estimation of the
      severity of mitral stenosis.

PMID- 22639922
TI  - A vignette study to examine health care professionals' attitudes towards patient
      involvement in error prevention.
AB  - BACKGROUND: Various authorities recommend the participation of patients in
      promoting patient safety, but little is known about health care professionals'
      (HCPs') attitudes towards patients' involvement in safety-related behaviours.
      OBJECTIVE: To investigate how HCPs evaluate patients' behaviours and HCP
      responses to patient involvement in the behaviour, relative to different aspects
      of the patient, the involved HCP and the potential error. DESIGN: Cross-sectional
      fractional factorial survey with seven factors embedded in two error scenarios
      (missed hand hygiene, medication error). Each survey included two randomized
      vignettes that described the potential error, a patient's reaction to that error
      and the HCP response to the patient. SETTING: Twelve hospitals in Switzerland.
      PARTICIPANTS: A total of 1141 HCPs (response rate 45%). MEASUREMENTS: Approval of
      patients' behaviour, HCP response to the patient, anticipated effects on the
      patient-HCP relationship, HCPs' support for being asked the question, affective
      response to the vignettes. Outcomes were measured on 7-point scales. RESULTS:
      Approval of patients' safety-related interventions was generally high and largely
      affected by patients' behaviour and correct identification of error. Anticipated
      effects on the patient-HCP relationship were much less positive, little
      correlated with approval of patients' behaviour and were mainly determined by the
      HCP response to intervening patients. HCPs expressed more favourable attitudes
      towards patients intervening about a medication error than about hand sanitation.
      CONCLUSIONS: This study provides the first insights into predictors of HCPs'
      attitudes towards patient engagement in safety. Future research is however
      required to assess the generalizability of the findings into practice before
      training can be designed to address critical issues.

PMID- 22639923
TI  - Rituximab-induced thrombocytopenia: a cohort study.
AB  - The combined information of drug exposure and laboratory test results on an
      individual patient level obtained in daily clinical practice can add important
      information about the safety of a drug. Thrombocytopenia is a known adverse drug
      reaction of rituximab, which has already been identified during the
      preregistration trials, but knowledge on incidence and risk factors in clinical
      practice is limited. We, therefore, aimed to estimate the incidence and explore
      the risk factors for the development of rituximab-induced thrombocytopenia (a
      platelet count, <100 * 10(9) platelets/L) in clinical practice. Ninety patients
      were eligible for inclusion of which 27 developed thrombocytopenia (cumulative
      incidence, 30%) within 30 days after administration of rituximab and 18 patients
      developed grade 3/4 thrombocytopenia (cumulative incidence, 20%). Patients with
      and without thrombocytopenia were compared to explore risk factors. Patients with
      a relatively low platelet count (217 vs. 324 * 10(9) /L, P = 0.011) before
      administration of rituximab had a higher risk for the development of
      thrombocytopenia, and although not statistically significant, patients treated
      with rituximab within the oncology setting (OR, 4.7; 95% CI, 1.0-23.3),
      independent of concomitant use of cytostatics, as compared to the autoimmune
      diseases and patients with a high platelet distribution width (PDW) (16.1 vs.
      15.8, P = 0.051). In conclusion, the incidence of rituximab-induced
      thrombocytopenia was higher than that identified during the clinical trials.
      Healthcare professionals should consider thrombocytopenia as a relevant reaction
      during treatment with rituximab. More frequent monitoring of the platelet count
      is especially advised in patients treated in the oncology indication and/or with
      a low platelet count and high PDW.

PMID- 22639924
TI  - Adolescent nutritional awareness and use of food labels: results from the
      National Nutrition Health and Examination Survey.
AB  - BACKGROUND: Awareness of federal nutrition programs and use of the nutrition
      facts label are associated with reduced risk for obesity and increased intake of
      fruits and vegetables. Relationships between nutrition programs, use of food
      labels and risk for overweight and obesity have rarely been evaluated in
      adolescents. METHODS: Using the National Health and Nutrition Examination Survey
      from 2005-6, we evaluated the frequency of nutrition awareness of USDA and CDC
      nutrition programs and use of food labels in adolescents. Risk for overweight
      (BMI >= 85-94th percentile) and obesity (BMI >= 95th percentile) was assessed in
      relation to nutrition awareness and label reading. RESULTS: Most adolescents
      (92.4%) were aware of the Food Guide Pyramid. Fewer (43.5%) were aware of the 5-A
      Day Program, and even less (29.3%) were aware of the Dietary Guidelines for
      Americans. Less than 25% of adolescents decided which foods to purchase by
      reading material on the nutrition facts label. There were significant racial and
      ethnic differences in awareness of federal nutrition programs with Mexican
      Americans having the lowest levels of awareness of the US Dietary Guidelines for
      Americans and the Food Guide Pyramid in comparison with other groups. Non
      Hispanic whites had higher and African-American adolescents had lower frequencies
      of reading fat information on the nutrition label in comparison to Mexican
      American and other Hispanics. Awareness of other nutrition programs or of other
      information on the nutrition facts label was not associated with increased or
      decreased risk for overweight or obesity. CONCLUSIONS: Use of the nutrition facts
      panel information is low among US adolescents. Additionally, less than half of
      adolescents are aware of federal nutrition programs including the Dietary
      Guidelines for Americans. Future studies should evaluate avenues to make
      nutrition information more accessible to young Americans.

PMID- 22639925
TI  - Genetic inactivation of the adenosine A(2A)  receptor exacerbates brain damage in
      mice with experimental autoimmune encephalomyelitis.
AB  - Studies with multiple sclerosis patients and animal models of experimental
      autoimmune encephalomyelitis (EAE) implicate adenosine and adenosine receptors in
      modulation of neuroinflammation and brain injury. Although the involvement of the
      A(1) receptor has been recently demonstrated, the role of the adenosine A(2A)
      receptor (A(2A)R) in development of EAE pathology is largely unknown. Using mice
      with genetic inactivation of the A(2A) receptor, we provide direct evidence that
      loss of the A(2A)R exacerbates EAE pathology in mice. Compared with wild-type
      mice, A(2A)R knockout mice injected with myelin oligodendroglia glycoprotein
      peptide had a higher incidence of EAE and exhibited higher neurological deficit
      scores and greater decrease in body weight. A(2A)R knockout mice displayed
      increased inflammatory cell infiltration and enhanced microglial cell activation
      in cortex, brainstem, and spinal cord. In addition, demyelination and axonal
      damage in brainstem were exacerbated, levels of Th1 cytokines increased, and Th2
      cytokines decreased. Collectively, these findings suggest that extracellular
      adenosine acting at A(2A)Rs triggers an important neuroprotective mechanism.
      Thus, the A(2A) receptor is a potential target for therapeutic approaches to
      multiple sclerosis.

PMID- 22639926
TI  - Receiving voluntary family planning services has no relationship with the
      paradoxical situation of high use of contraceptives and abortion in Vietnam: a
      cross-sectional study.
AB  - BACKGROUND: Vietnam shows a paradoxical situation where high contraceptive
      prevalence goes together with high abortion rates. This study examined the
      associations between self-reports of having received voluntary family planning
      (VFP) services and induced abortions. METHODS: A cross sectional survey was
      conducted in Thai Nguyen province, covering a total of 1281 women. Data were
      derived from a sample of 935 married women aged 18-49 years who were ever-users
      (93.5%) and current users of contraceptives (84%), and had completed birth
      histories. The dependent variables were the likelihood of having an induced
      abortion and repeated (two or more) induced abortions. The main independent
      variable was having received the three VFP dimensions (counselling, broader
      information, and access to availability). The association was examined using
      multivariate logistic regressions, taking into account women's socio-demographic
      characteristics. RESULTS: The overall induced abortion percentage was 19.4 per
      100 pregnancies. None of the three VFP dimensions was significantly associated
      with the odds of having an induced abortion or having repeated induced abortions.
      Mother's age of 35 or older, having more than three living children, and ever
      used female contraception methods significantly doubled or more the odds of
      having an induced abortion and significantly tripled the odds of having repeated
      abortions. CONCLUSIONS: Results indicate that women receiving VFP services were
      not less likely to have induced abortions. The provision of family planning
      counselling, information on contraceptive method mix, and management skills to
      ensure availability, are in need of reinforcement in a new set of policy and
      program strategies in the future.

PMID- 22639927
TI  - Low-ammonia niche of ammonia-oxidizing archaea in rotating biological contactors
      of a municipal wastewater treatment plant.
AB  - The first step of nitrification is catalysed by both ammonia-oxidizing bacteria
      (AOB) and archaea (AOA), but physicochemical controls on the relative abundance
      and function of these two groups are not yet fully understood, especially in
      freshwater environments. This study investigated ammonia-oxidizing populations in
      nitrifying rotating biological contactors (RBCs) from a municipal wastewater
      treatment plant. Individual RBC stages are arranged in series, with nitrification
      at each stage creating an ammonia gradient along the flowpath. This RBC system
      provides a valuable experimental system for testing the hypothesis that ammonia
      concentration determines the relative abundance of AOA and AOB. The results
      demonstrate that AOA increased as ammonium decreased across the RBC flowpath, as
      indicated by qPCR for thaumarchaeal amoA and 16S rRNA genes, and core lipid (CL)
      and intact polar lipid (IPL) crenarchaeol abundances. Overall, there was a
      negative logarithmic relationship (R(2) =0.51) between ammonium concentration and
      the relative abundance of AOA amoA genes. A single AOA population was detected in
      the RBC biofilms; this phylotype shared low amoA and 16S rRNA gene homology with
      existing AOA cultures and enrichments. These results provide evidence that
      ammonia availability influences the relative abundances of AOA and AOB, and that
      AOA are abundant in some municipal wastewater treatment systems.

PMID- 22639928
TI  - Investigation of zoonotic infections among Auckland Zoo staff: 1991-2010.
AB  - Investigation was undertaken to assess the occurrence of zoonotic infection among
      staff at Auckland Zoological Park, New Zealand, in 1991, 2002 and 2010. Serial
      cross-sectional health surveys in 1991, 2002 and 2010 comprising a health
      questionnaire, and serological, immunological and microbiological analysis for a
      range of potential zoonotic infections were performed. Laboratory results for zoo
      animals were also reviewed for 2004-2010 to assess the occurrence of potential
      zoonotic infections. Veterinary clinic, animal handler, grounds, maintenance and
      administrative staff participated in the surveys, with 49, 42 and 46 participants
      in the 1991, 2002 and 2010 surveys, respectively (29% of total zoo staff in
      2010). A small number of staff reported work-related infections, including
      erysipelas (1), giardiasis (1) and campylobacteriosis (1). The seroprevalence of
      antibodies to hepatitis A virus and Toxoplasma gondii closely reflected those in
      the Auckland community. No carriage of hepatitis B virus (HBV) was detected, and
      most of those with anti-HBV antibodies had been vaccinated. Few staff had
      serological evidence of past leptospiral infection. Three veterinary clinic staff
      had raised Chlamydophila psittaci antibodies, all < 1 : 160 indicating past
      exposure. Two staff (in 1991) had asymptomatic carriage of Giardia lamblia and
      one person (in 2010) had a dermatophyte infection. After 1991, positive tests
      indicating exposure to Mycobacterium tuberculosis were < 10%, comparable to the
      general New Zealand population. Zoo animals had infections with potential
      zoonotic agents, including G. lamblia, Salmonella spp., Campylobacter spp. and T.
      gondii, although the occurrence was low. Zoonotic agents pose an occupational
      risk to zoo workers. While there was evidence of some zoonotic transmission at
      Auckland Zoo, this was uncommon and risks appear to be adequately managed under
      current policies and procedures. Nevertheless, ongoing assessment of risk factors
      is needed as environmental, human and animal disease and management factors
      change. Policies and procedures should be reviewed periodically in conjunction
      with disease monitoring results for both animals and staff to minimise zoonotic
      transmission.

PMID- 22639929
TI  - 'Y'Scenedesmus (Chlorophyta, Chlorophyceae): the internal transcribed spacer 2
      rRNA secondary structure re-revisited.
AB  - Including RNA secondary structures improves accuracy and robustness in
      reconstruction of phylogenetic trees. It is possible to simultaneously infer
      alignments and phylogenies on the primary sequence and the secondary structure
      information. For the internal transcribed spacer 2 (ITS2), a phylogenetic RNA
      transcript marker, two different structure conformations (I or Y shape for helix
      I) were published for Scenedesmaceae, and a third appeared in the ITS2 database.
      We contrast the effects on phylogenetic tree reconstruction of different
      structure sets for a small scenedesmacean subset, using neighbour-joining,
      maximum parsimony and, for the first time, maximum likelihood, on sequence
      structure alignments. Generally our study supports inclusion of secondary
      structure information. However, we found that any of the three structure
      conformations is equally fit for phylogenetic studies, but prefer the I shape for
      helix I. Moreover, our results enable us to give general recommendations on how
      to build a phylogenetic tree using ITS2 sequence-structure alignments, including
      different methods to obtain the secondary structures. Thus, we hope to provide a
      valuable contribution not only for scenedesmacean ITS2 phylogeny, but also for
      other approaches using RNA transcript markers.

PMID- 22639930
TI  - Risk of inflammatory bowel disease following a diagnosis of irritable bowel
      syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD)
      symptoms often overlap. In some IBS cases there are subtle inflammatory changes
      similar to the immune-mediated pathophysiology of IBD, and the risk of both
      increases after infectious gastroenteritis (IGE). METHODS: To evaluate the effect
      of IBS and IGE on IBD risk utilizing US Department of Defense medical encounter
      data, active duty personnel with IBS were matched to subjects without IBS.
      Medical encounter history was analyzed to assess for incident IBD. IGE was
      identified from documented medical encounters and by self-report. Relative risks
      were calculated using Poisson regression models. RESULTS: We identified 9,341
      incident IBS cases and 18,678 matched non-IBS subjects and found an 8.6-fold
      higher incidence (p < 0.0001) of IBD among those with IBS (238.1 per 100,000
      person-years) compared to our referent population (27.8 per 100,000 person
      years). In a subset (n = 2,205) of well-defined IBS cases, IBD risk was 15 times
      that of subjects without IBS. The median time between IBS and IBD diagnoses was
      2.1 years. IGE also increased IBD risk approximately 2-fold ( p < 0.05) after
      controlling for IBS. CONCLUSIONS: These data reflect a complex interaction
      between illness presentation and diagnosis of IBS and IBD and suggest
      intercurrent IGE may increase IBD risk in IBS patients. Additional studies are
      needed to determine whether IBS lies on the causal pathway for IBD or whether the
      two are on a pathophysiological spectrum of the same clinical illness. These data
      suggest consideration of risk reduction interventions for IGE among IBS patients
      at high disease risk.

PMID- 22639931
TI  - The effects of age and focality on delay-execute prospective memory.
AB  - In everyday prospective remembering, individuals must often delay the execution
      of a retrieved intention until they are in the appropriate setting. These so
      called 'delay-execute' tasks are particularly troublesome for older adults, who
      consistently demonstrate impaired performance in this kind of laboratory task. To
      better understand this effect, we investigated delay-execute prospective memory
      performance in younger and older adults. Specifically, we examined the strategies
      individuals used to maintain intentions over a delay period by analyzing response
      times to the ongoing task, both before and after the cue event. The results
      suggest that younger and older individuals perform the task similarly by
      rehearsing or reformulating the intention. Despite performing the task in a
      similar manner, older adults showed greater impairments in delay-execute
      prospective remembering.

PMID- 22639932
TI  - The Arabidopsis DCP2 gene is required for proper mRNA turnover and prevents
      transgene silencing in Arabidopsis.
AB  - Post-transcriptional gene silencing often limits the over-expression of
      transgenes in transgenic plants. It involves RNA-DEPENDENT RNA POLYMERASE 6
      (RDR6), which recognizes aberrant transcripts, such as inaccurately processed or
      uncapped mRNA, and triggers silencing of target transcripts. Here, we describe
      the isolation and characterization of an Arabidopsis mutant displaying increased
      transgene silencing (its1). Reduced accumulation of transgene mRNA in the its1
      mutant background was accompanied by accumulation of transgene-specific siRNAs
      and was overcome by potyvirus infection. We therefore speculated that ITS1 is a
      suppressor of post-transcriptional gene silencing. Map-based cloning and
      subsequent complementation revealed that ITS1 encodes DECAPPING 2 (DCP2), which
      is crucial for decapping, a prerequisite for mRNA degradation. In agreement with
      the proposed function of DCP2, we found a reduced accumulation of uncapped mRNA
      in the its1 mutant. Furthermore, silencing in the its1 mutant was dependent on
      RDR6 function, suggesting that reduced decapping leads to accumulation of
      aberrant capped mRNA. Hence, we provide evidence for a class of aberrant mRNA
      that accumulates upon impaired mRNA decapping and triggers post-transcriptional
      gene silencing in Arabidopsis. As DCP2 knockouts cause post-embryo lethality, we
      isolated a hypomorphic dcp2 allele, providing insights into mRNA degradation and
      its interplay with post-transcriptional gene silencing.

PMID- 22639933
TI  - Skin-of-color epidemiology: a report of the most common skin conditions by race.
AB  - To quantify and compare diagnoses according to race in pediatric Health
      Maintenance Organization (HMO) health plan patients seen in a general dermatology
      clinic over a 10-year period. Retrospective cohort of health plan pediatric
      patients seen in the dermatology clinic between 1997 and 2007 was established
      using an electronic medical record database. Diagnoses and diagnostic codes were
      recorded according to International Classification of Diseases, Ninth Revision
      (ICD-9) diagnostic codes grouped on their first three digits. The proportion of
      patients with each diagnosis was determined according to race and sex, and the 10
      most common diagnoses were determined. The most common diagnoses observed in all
      pediatric patients were acne (28.6%), dermatitis (19.4%), and warts (16.2%),
      accounting for more than 60% of dermatologic visits by children. Although acne
      (29.9%), warts (22.6%), and dermatitis (13.1%) were also the most common
      diagnoses for Caucasian children, African American pediatric patients were most
      commonly seen for dermatitis (29.0%), acne (27.5%), and dermatophytosis (10.2%).
      The three most common diagnoses for Asian patients were dermatitis (29.1%), acne
      (22.2%), and warts (12.6%). Acne remains one of the most common dermatologic
      diagnoses in children of all races. Differences in frequency of office visits for
      dermatitis, warts, and dermatophytosis were seen when comparing children of other
      races with Caucasian children.

PMID- 22639934
TI  - Formulation, characterization and in vitro-in vivo evaluation of flurbiprofen
      loaded nanostructured lipid carriers for transdermal delivery.
AB  - Flurbiprofen is used in the treatment of arthritis. However, its multiple dosing
      due to short elimination half life is a concern for such treatment. This work
      aims to develop nanostructured lipid carriers (NLCs) of flurbiprofen and evaluate
      their potential for transdermal delivery. The NLCs were prepared by the optimized
      o/w emulsification-homogenization-sonication technique using coconut oil (liquid
      lipid). The NLCs were found to be spherical with uniform size (214 nm). The
      entrapment efficiency and zeta potential were 92.58% and -30.70 mV, respectively.
      Differential scanning calorimetry (DSC) showed the amorphous state of
      flurbiprofen encapsulated in NLCs. The percentage cumulative drug release through
      the excised rat skin from NLCs was biphasic and significantly prolonged compared
      with the commercial gel. DSC of the treated skin indicated that the NLCs
      penetrate into follicles of the skin and accumulate in the dermis. The
      bioavailability of flurbiprofen from NLCs was more than 1.7-fold that of the
      commercial gel. The NLCs showed a quick onset and sustained anti-inflammatory
      effect over period of 24 h for carrageenan-induced rat paw edema than the
      commercial gel. The stability data revealed that the NLCs were more stable when
      stored at 5 degrees C. In conclusion, prepared NLCs have potential for skin
      targeting and sustained drug release.

PMID- 22639935
TI  - More roundabouts and reduced vehicle emissions?

PMID- 22639936
TI  - Model uncertainty and multimodel inference in reliability estimation within a
      longitudinal framework.
AB  - Laenen, Alonso, and Molenberghs (2007) and Laenen, Alonso, Molenberghs, and
      Vangeneugden (2009) proposed a method to assess the reliability of rating scales
      in a longitudinal context. The methodology is based on hierarchical linear
      models, and reliability coefficients are derived from the corresponding
      covariance matrices. However, finding a good parsimonious model to describe
      complex longitudinal data is a challenging task. Frequently, several models fit
      the data equally well, raising the problem of model selection uncertainty. When
      model uncertainty is high one may resort to model averaging, where inferences are
      based not on one but on an entire set of models. We explored the use of different
      model building strategies, including model averaging, in reliability estimation.
      We found that the approach introduced by Laenen et al. (2007, 2009) combined with
      some of these strategies may yield meaningful results in the presence of high
      model selection uncertainty and when all models are misspecified, in so far as
      some of them manage to capture the most salient features of the data.
      Nonetheless, when all models omit prominent regularities in the data, misleading
      results may be obtained. The main ideas are further illustrated on a case study
      in which the reliability of the Hamilton Anxiety Rating Scale is estimated.
      Importantly, the ambit of model selection uncertainty and model averaging
      transcends the specific setting studied in the paper and may be of interest in
      other areas of psychometrics.

PMID- 22639937
TI  - Association of quality of life with major depressive disorder among people with
      HIV in South India.
AB  - Depression in people with HIV has wide-spread implications related to faster
      progression to AIDS, poor drug compliance, and lower quality of life (QOL).
      Although there have been studies that have examined the role of sociodemographic
      variables in people with HIV, there have only been a few on the assessment of QOL
      and its association with depression among people with HIV in South India. The
      objectives of this study were to diagnose major depressive disorder (MDD) and
      examine the association of depression with health-related quality of life (HRQOL)
      among people with HIV in coastal South India. Structured questionnaires detailing
      sociodemographic and HIV related variables were filled out by 103 patients with
      HIV attending a tertiary care center. Interviews were carried out by a
      psychiatrist to diagnose ICD-10 MDD and a clinical psychologist to rate the
      severity of depression using the Hamilton Depression Scale (HAMD). Subjective
      HRQOL was assessed using HIV/AIDS targeted quality of life questionnaire in these
      patients. Fifty patients were diagnosed with MDD. Among them, 23 (46%) were
      mildly depressed, 19 (38%) were moderately depressed, 7 (14%) were severely
      depressed, and 1 (2%) was very severely depressed. Mean QOL scores for all
      dimensions except sexual function were significantly and inversely correlated
      (p<0.05) with HAMD implying that patients with greater severity of depressive
      symptoms had poorer HRQOL. Individuals with ICD-10 diagnosis of MDD presented
      significantly lower scores of QOL compared to individuals without MDD. The
      implication is that early diagnosis and referral of depressed patients needs to
      be incorporated into intervention programs to improve patient outcomes and QOL.
      More research is needed to investigate the impact of antidepressant therapy on
      QOL using this study as a comparison group in a similar population.

PMID- 22639938
TI  - A long-term study of a patient with anti-p200 pemphigoid: correlation of
      autoantibody levels with disease activity and an example of epitope spreading.
AB  - Anti-p200 pemphigoid is a rare subepidermal blistering disease associated with
      autoantibodies against a 200-kDa protein, reportedly corresponding to laminin
      gamma1. However, direct evidence of the pathogenic potential of these antibodies
      has not been proven. For 5 years we have followed up a patient with anti-p200
      pemphigoid. During this period she experienced a total of three generalized
      relapses. Quantifying our patient's autoantibody concentrations against laminin
      gamma1 by enzyme-linked immunosorbent assay throughout the course of her disease
      we demonstrated a clear correlation with disease activity, thus providing the
      first evidence of the possible pathogenic role of antibodies against laminin
      gamma1 in anti-p200 pemphigoid. Further analysis by Western blotting revealed the
      occurrence of additional autoantibodies against the alpha3 chain of laminin 332,
      1.5 years after diagnosis, suggestive of intermolecular epitope spreading. Yet,
      the clinical appearance was unchanged and mucous membranes remained unaffected at
      any stage of the disease.

PMID- 22639939
TI  - Revisiting the rise and fall of false recall: presentation rate effects depend on
      retention interval.
AB  - Leading theories of false memory predict that veridical and false recall of lists
      of semantically associated words can be dissociated by varying the presentation
      speed during study. Specifically, as presentation rate increases from
      milliseconds to seconds, veridical recall is predicted to increase monotonically
      while false recall is predicted to show a rapid rise and then a slow decrease--a
      pattern shown by McDermott and Watson (2001) in a study using immediate recall
      tests. In three experiments we tested the generality of the effects of rapid
      presentation rates on veridical and false memory. In Experiments 1 and 2
      participants exhibited high levels of false recall on a delayed recall test, even
      for very fast stimulus onset asynchronies (SOA)--contrary to predictions from
      leading theories of false memory. When we switched to an immediate recall test in
      Experiment 3 we replicated the pattern predicted by the theories and observed by
      McDermott and Watson. Follow-up analyses further showed that the relative output
      position of false recalls is not affected by presentation rate, contrary to
      predictions from fuzzy trace theory. Implications for theories of false memory,
      including activation monitoring theory and fuzzy trace theory, are discussed.

PMID- 22639940
TI  - Influence of flow on longevity of superhydrophobic coatings.
AB  - Previous studies have demonstrated the capability of superhydrophobic surfaces to
      produce slip flow and drag reduction, which properties hold considerable promise
      for a broad range of applications. However, in order to implement such surfaces
      for practical utilizations, environmental factors such as water movement over the
      surface must be observed and understood. In this work, experiments were carried
      out to present a proof-of-concept study on the impact of flow on longevity of
      polystyrene fibrous coatings. The time-dependent hydrophobicity of a submerged
      coating in a pressure vessel was determined while exposing the coating to a
      rudimentary wall-jet flow. Rheological studies were also performed to determine
      the effect of the flow on drag reduction. The results show that the longevity of
      the surface deteriorates by increasing the flow rate. The flow appears to enhance
      the dissolution of air into water, which leads to a loss of drag reduction.

PMID- 22639941
TI  - Exogenous vascular endothelial growth factor supplementation can restore the
      podocyte barrier-forming capacity disrupted by sera of preeclamptic women.
AB  - AIM: To determine whether exogenous vascular endothelial growth factor (VEGF)
      supplementation to sera from women with preeclampsia can restore the podocyte
      barrier-forming capacity disrupted after stimulation with sera from these women.
      MATERIAL AND METHODS: Enzyme-linked immunosorbent assays (ELISAs) for sFlt-1
      (soluble VEGF receptor 1) and VEGF were performed in the sera of preeclamptic and
      healthy pregnant women. VEGF-enriched preeclamptic serum was used to evaluate the
      capacity of such sera to restore the diminished podocyte barrier capacity
      secondary to stimulation with untreated preeclamptic sera. RESULTS: Two groups,
      preeclampsia (n=15) and healthy (n=15) pregnant women, were established. Median
      serum levels (pg/mL) of sFlt-1 and VEGF were significantly different between
      groups: 3987 versus 1432 and 6 versus 15.6 (P<0.001). Altered resistance values
      of podocytes stimulated with sera from women with preeclampsia were recovered
      after exogenous VEGF supplementation. CONCLUSION: The mean resistance value of
      cultured podocytes, an indicator of the integrity of the cytoskeleton and the
      capacity of these cells to form layers, is altered in women with preeclampsia.
      High levels of sFlt-1, an inhibitor of VEGF observed in high concentrations in
      the serum of these patients, could be the underlying cause of this alteration. We
      provide evidence that exogenous VEGF supplementation of the sera of these women
      could recover this indicator.

PMID- 22639942
TI  - Prostate cancer diagnosis is associated with an increased risk of erectile
      dysfunction after prostate biopsy.
AB  - OBJECTIVE: To evaluate prospectively the characteristics, erectile function and
      lower urinary tract symptoms (LUTS) of men undergoing prostate needle biopsy
      (PNBx). PATIENTS AND METHODS: From 2008 to 2011, 134 men were prospectively
      administered the International Index of Erectile Function (IIEF), American
      Urological Association Symptom Index (AUA-SI), and quality-of-life (QoL)
      questionnaires before and after undergoing a single 12-core PNBx. Comparisons of
      IIEF and AUA-SI scores before and after PNBx, based upon baseline characteristics
      and prostate cancer (PCa) diagnosis, were performed. Univariable and
      multivariable logistic regression models were used to characterize predictors of
      change in IIEF scores. RESULTS: In the 85 men who fulfilled the inclusion
      criteria, there were no significant differences between the mean (sd) total pre
      biopsy and the mean (sd) post-biopsy IIEF scores: 57.8 (12.9) vs 54.3 (17.2).
      Subgroup analysis showed that men who had biopsy-proven PCa had significantly
      greater changes in their post-biopsy IIEF scores compared with men without (-10.1
      vs. 1.0; P < 0.001). After specific analyses of the IIEF domains in these groups
      we found significant decreases in every domain, including erectile function (P =
      0.01). On multivariate analyses, only PCa diagnosis was associated with a
      significant change in IIEF (odds ratio 7.2; P = 0.003). There were no differences
      in AUA-SI or QoL scores in the overall population or in subgroups. CONCLUSIONS:
      Cancer diagnosis appears to have an adverse effect on the erectile function of
      men undergoing PNBx but no effect on LUTS. This study highlights a potential
      negative psychological confounder that may influence erectile function before the
      treatment of PCa. Additional prospective trials evaluating these relationships
      are warranted.

PMID- 22639943
TI  - MRCISD studies of the dissociation of vinylhydroperoxide, CH2CHOOH: there is a
      saddle point.
AB  - Multireference ab initio methods are used to investigate the dissociation of
      vinylhydroperoxide CH(2)CHOOH into vinyl oxide and hydroxide radicals. In
      contrast to some previous studies, which claim the reaction has no saddle point,
      our calculations confirm that the dissociation is associated with a kinetic
      barrier (transition state). We further propose the existence of a hitherto
      undiscovered radical-radical complex on the reaction path. The computed reaction
      energetics are used to estimate VHP dissociation rates, and the results are
      discussed in the context of atmospheric ozonolysis pathways. Qualitative aspects
      of the dissociation of larger, substituted vinylhydroperoxides are also
      discussed.

PMID- 22639944
TI  - The effect of yoga on women with secondary arm lymphoedema from breast cancer
      treatment.
AB  - BACKGROUND: Women who develop secondary arm lymphoedema subsequent to treatment
      associated with breast cancer require life-long management for a range of
      symptoms including arm swelling, heaviness, tightness in the arm and sometimes
      the chest, upper body impairment and changes to a range of parameters relating to
      quality of life. While exercise under controlled conditions has had positive
      outcomes, the impact of yoga has not been investigated. The aim of this study is
      to determine the effectiveness of yoga in the physical and psycho-social domains,
      in the hope that women can be offered another safe, holistic modality to help
      control many, if not all, of the effects of secondary arm lymphoedema. METHODS
      AND DESIGN: A randomised controlled pilot trial will be conducted in Hobart and
      Launceston with a total of 40 women receiving either yoga intervention or current
      best practice care. Intervention will consist of eight weeks of a weekly teacher
      led yoga class with a home-based daily yoga practice delivered by DVD. Primary
      outcome measures will be the effects of yoga on lymphoedema and its associated
      symptoms and quality of life. Secondary outcome measures will be range of motion
      of the arm and thoracic spine, shoulder strength, and weekly and daily physical
      activity. Primary and secondary outcomes will be measured at baseline, weeks
      four, eight and a four week follow up at week twelve. Range of motion of the
      spine, in a self-nominated group, will be measured at baseline, weeks eight and
      twelve. A further outcome will be the women's perceptions of the yoga collected
      by interview at week eight. DISCUSSION: The results of this trial will provide
      information on the safety and effectiveness of yoga for women with secondary arm
      lymphoedema from breast cancer treatment. It will also inform methodology for
      future, larger trials. TRIAL REGISTRATION: ACTRN12611000202965.

PMID- 22639945
TI  - Rare neonatal diabetes insipidus and associated late risks: case report.
AB  - BACKGROUND: Most cases of neonatal central diabetes insipidus are caused by an
      injury, which often results in other handicaps in the patient. The infant's
      prognosis will be determined by his or her own early age and disability as well
      as by the physician's skill. However, the rarity of this condition prevents the
      acquisition of personal experience dealing with it. CASE PRESENTATION: A neonatal
      hemorrhagic stroke, caused by an aortic coarctation, caused right lower limb
      paresis, swallowing disability, and central diabetes insipidus in a term infant.
      The scant oral intake, as a consequence of his disability, caused progressive
      undernutrition which closed a vicious circle, delaying his development and his
      ability to overcome the swallowing handicap. On the other hand, nasal
      desmopressin absorption was blocked by several common colds, resulting in brain
      bleeding because of severe dehydration. This even greater brain damage hampered
      the improvement of swallowing, closing a second harmful circle. Moreover, a
      devastating central myelinolysis with quadriplegia, caused by an uncontrolled
      intravenous infusion, consummated a pernicious sequence, possibly unreported.
      CONCLUSIONS: The child's overall development advanced rapidly when his nutrition
      was improved by gastrostomy: This was a key effect of nutrition on his highly
      sensitive neurodevelopment. Besides, this case shows potential risks related to
      intranasal desmopressin treatment in young children.

PMID- 22639946
TI  - Use of phytoplankton-derived dissolved organic carbon by different types of
      bacterioplankton.
AB  - Phytoplankton and heterotrophic prokaryotes are major components of the microbial
      food web and interact continuously: heterotrophic prokaryotes utilize the
      dissolved organic carbon derived from phytoplankton exudation or cell lysis
      (DOCp), and mineralization by heterotrophic prokaryotes provides inorganic
      nutrients for phytoplankton. For this reason, these communities are expected to
      be closely linked, although the study of the interactions between them is still a
      major challenge. Recent studies have presented interactions between phytoplankton
      and heterotrophic prokaryotes based on coexistence or covariation throughout a
      time-series. However, a real quantification of the carbon flow within these
      networks (defined as the interaction strength, IS) has not been achieved yet.
      This is critical to understand the selectivity degree of bacteria responding to
      specific algal DOCp. Here we used microautoradiography to quantify the
      preferences of the major heterotrophic prokaryote phylogenetic groups on DOC
      derived from several representative phytoplankton species, and expressed these
      preferences as an IS value. The distribution of the ISs was not random but rather
      skewed towards weak interactions, in a similar way as the distributions described
      for stable complex non-microbial ecosystems, indicating that there are some cases
      of high specificity on the use of specific algal DOCp by some bacterial groups,
      but weak interactions are more common and may be relevant as well. The variety of
      IS patterns observed supports the view that the vast range of different resources
      (different types of organic molecules) available in the sea selects and maintains
      the high levels of diversity described for marine bacterioplankton.

PMID- 22639947
TI  - Angptl4 maintains in vivo repopulation capacity of CD34+ human cord blood cells.
AB  - OBJECTIVES: Methods to expand hematopoietic stem cells (HSCs) ex vivo encompass
      an attractive approach that would substantially broaden the clinical
      applicability of HSCs derived from cord blood (CB). Recently, members of the
      angiopoietin-like (Angptl) family of growth factors were shown to expand both
      murine and human HSCs. Specifically, Angptl5 has been implicated in the expansion
      of human NOD/SCID-repopulating cells (SRCs) ex vivo. Here, we sought to evaluate
      the potential of additional Angptls to expand human SRCs from CB. Additionally,
      the purpose of this study was to evaluate the reproducibility of Angptl-mediated
      expansion of SRCs across independent experiments. METHODS: Human CD34(+) cells
      from CB were cultured in vitro for eleven or 8 d in the presence or absence of
      Angptls. The reconstitution capacity of expanded cells was subsequently measured
      in vivo by transplantation into NOD/SCID or NSG mice and compared with that of
      uncultured cells. RESULTS: We report here that Angptl4 functions to maintain SRC
      activity of CD34(+) CB-derived cells ex vivo as assayed in NOD/SCID and NSG mice.
      However, all Angptls tested, including Angptl1, Angptl4, and Angptl5, were
      associated with variation between experiments. CONCLUSION: Our findings indicate
      that Angptl4 and Angptl5 can lead to increased engraftment capacity of SRCs, but
      more frequently, these factors are associated with maintenance of SRC activity
      during ex vivo culture. Thus, Angptl-mediated expansion of SRCs ex vivo is
      associated with more interexperimental variation than previously thought. We
      conclude that Angptls would be useful in instances where there is a need to
      maintain HSCs ex vivo, such as during transduction for gene therapy applications.

PMID- 22639948
TI  - Constitutively active mutant gives novel insights into the mechanism of bitter
      taste receptor activation.
AB  - The human bitter taste receptors (T2Rs) belong to the G-protein coupled receptor
      (GPCR) superfamily. T2Rs share little homology with the large subfamily of Class
      A G-protein coupled receptors, and their mechanisms of activation are poorly
      understood. Guided by biochemical and molecular approaches, we identified two
      conserved amino acids Gly281.46 and Ser2857.47 present on transmembrane (TM)
      helices, TM1 and TM7, which might play important roles in T2R activation.
      Previously, it was shown that naturally occurring Gly511.46 mutations in the dim
      light receptor, rhodopsin, cause autosomal dominant retinitis pigmentosa, with
      the mutants severely defective in signal transduction. We mutated Gly281.46 and
      Ser2857.47 in T2R4 to G28A, G28L, S285A, S285T, and S285P, and carried out
      pharmacological characterization of the mutants. No major changes in signaling
      were observed upon mutation of Gly281.46 in T2R4. Interestingly, S285A mutant
      displayed agonist-independent activity (approximately threefold over basal wild
      type T2R4 or S285T or S285P). We propose that Ser2857.47 stabilizes the inactive
      state of T2R4 by a network of hydrogen-bonds connecting important residues on TM1
      TM2-TM7. We compare and contrast this hydrogen-bond network with that present in
      rhodopsin. Thus far, S285A is the first constitutively active T2R mutant
      reported, and gives novel insights into T2R activation.

PMID- 22639949
TI  - European pet travel: misleading information from veterinarians and government
      agencies.
AB  - Inter-country travel of companion animals provides an opportunity for
      introduction of zoonotic pathogens, such as rabies virus and Echinococcus spp.
      Regulations are in place to control this threat, but Schengen Agreements mean
      that border controls between some European countries are minimal, and animals may
      enter countries without any checks that they have been appropriately treated.
      Veterinarians provide an important source of information for people intending to
      travel with their pets. We conducted a telephone survey to investigate provision
      of correct advice to someone intending to travel with their dog to Norway.
      Mainland Norway is considered free of both rabies and E. multilocularis and is a
      signatory to the Schengen Agreement. Ten randomly selected veterinary clinics
      were surveyed in Austria, Belgium (Wallonia), Finland, France, Germany, Norway,
      Sweden, Switzerland and United Kingdom. The information provided was scored as
      correct, incorrect or incomplete. The information provided by secondary
      information sources (website or government agency), which the clinic had referred
      the caller to, was also assessed (correct, incorrect, incomplete). Whilst the
      majority of clinics provided appropriate information regarding rabies, many
      clinics did not provide correct information regarding treatment for E.
      multilocularis. Less than one in 10 clinics provided the correct information
      regarding both pathogens directly at the time of calling. The correct information
      was obtained, once taking into account secondary sources, just 62% of the time.
      Countrywise, most clinics in Finland provided correct advice, either directly or
      indirectly via referring the caller to another source, whilst the majority in
      Belgium, Germany and France did not. The apparent paucity of readily accessible,
      correct advice for owners intending to travel with their dogs is concerning. The
      compulsory treatment regulations are only as good as the checks that ensure
      compliance, and this is also lacking in some countries.

PMID- 22639950
TI  - Trends and variations in infant mortality among 47 prefectures in Japan.
AB  - OBJECTIVES: To determine IMR trends and regional variations among 47 prefectures
      in Japan and to identify associated population-based factors. METHODS: We
      conducted an ecological study of infant mortality rate (IMR) by analyzing
      publicly available data from the Ministry of Health, Labour and Welfare of Japan.
      Outcome measure for trend is the IMR for each of 47 prefectures from 1999 to
      2007; for variation, IMRs for 2006 and 2007 in each prefecture were averaged. We
      considered as covariates prefecture-level variables related to public health,
      socio-economic status, clinical services and health care facilities. We conducted
      multivariate statistical analyses to determine covariates most strongly
      associated with both 1999-2007 IMR trends and 2006-2007 IMR. RESULTS: The mean
      IMR decreased from 3.42 deaths per 1000 live births (range 2.1 to 5.1) in 1999 to
      2.54 (range 1.5 to 4.4) in 2007; reductions were greater in prefectures with
      higher concentrations of public health nurses (PHNs) and nurses. In 2006-2007,
      nine prefectures had IMRs <= 2.25; eight had IMRs >= 3.0. When low-, moderate-
      and high-IMR prefectures were compared, per capita PHNs, maternal education,
      centralized water supply and household income were identified as significant
      covariates. CONCLUSIONS: Both national and prefecture-level IMR in Japan
      decreased from 1999 to 2007; however, the degree of reduction varied by
      prefecture. Given that more nurses and PHNs per capita were associated with
      greater IMR reductions from 1999 to 2007 and more PHNs with lower 2006-2007 IMRs,
      distribution of preventive health services may play a major role in reducing
      regional disparities in IMR.

PMID- 22639951
TI  - Melatonin regulates the calcium-buffering proteins, parvalbumin and hippocalcin,
      in ischemic brain injury.
AB  - Melatonin has anti-oxidant activity and it exerts a neuroprotective effects
      during ischemic brain injury. Calcium-buffering proteins including parvalbumin
      and hippocalcin are involved in neuronal differentiation and maturation through
      calcium signaling. This study investigated whether melatonin moderates
      parvalbumin and hippocalcin expression in cerebral ischemia and glutamate
      toxicity-induced neuronal cell death. Focal cerebral ischemia was induced by
      middle cerebral artery occlusion (MCAO). Male Sprague-Dawley rats were treated
      with vehicle or melatonin (5 mg/kg) prior to MCAO, and cerebral cortical tissues
      were collected 24 hr after MCAO. Parvalbumin and hippocalcin levels were
      decreased in vehicle-treated animal with MCAO, whereas melatonin prevented the
      ischemic injury-induced reduction in these proteins. In cultured hippocampal
      cells, glutamate toxicity decreased parvalbumin and hippocalcin levels, while
      melatonin treatment prevented the glutamate exposure-induced diminished in these
      proteins levels. Melatonin also attenuated the glutamate toxicity-induced
      increase in intracellular Ca(2+) levels. These results suggest that the
      maintenance of parvalbumin and hippocalcin levels by melatonin in ischemic injury
      contributes to the neuroprotective effect of melatonin against neuronal cell
      damage.

PMID- 22639952
TI  - Comparison of visual assessments versus planimetry assessments in a large-scale
      clinical trial of onychomycosis.
AB  - BACKGROUND: Computerized nail planimetry is an objective means of accurately
      assessing affected nail areas, versus the standard visual estimation method.
      However, no published comparison of visual assessment with planimetry is
      currently available on onychomycosis to support this recommendation. OBJECTIVES:
      This article evaluates efficacy based on visual assessment compared to planimetry
      measures during the course of an 84-week large-scale, single-site trial of
      subungual dermatophyte onychomycosis, to determine the validity of planimetry
      versus visual assessment. METHODS: Visually assessed percentage of affected area
      of the target toenail was compared with planimetry calculated measurements made
      from digital photographs. RESULTS: Comparison showed good statistical agreement
      of visual and planimetry measures based on correlation coefficient. Visual and
      planimetry assessments at week 84 were within 10% of each other in 92% of cases,
      and within 5% of each other in 74% of comparisons. However, errors in visual
      assessment artificially inflated the cure rates by 9% and 11% at weeks 84 and 48,
      respectively. Furthermore, the significant difference in effective cure between
      regimens using visual methods loses significance when planimetry measures are
      used. CONCLUSIONS: The results suggest that objective measures such as planimetry
      will reduce the impact of visual assessment errors, and techniques to increase
      the standardization of onychomycosis assessment are warranted.

PMID- 22639953
TI  - Cutaneous lupus after herpes zoster: isomorphic, isotopic, or both?
AB  - Koebner isomorphic response describes the phenomenon of histopathologically
      identical skin lesions of a preceding cutaneous disease appearing in sites of
      trauma. Wolf isotopic response describes the phenomenon of a new skin disease
      appearing in the site of an unrelated cutaneous disease. Neither of the phenomena
      has been reported in relation to systemic lupus erythematosus. This report
      describes a 17-year-old girl with systemic lupus erythematosus exhibiting
      particularly severe cutaneous involvement confined primarily to sun-exposed areas
      presenting with a dermatomal band of atrophic, scaling, erythematous papules, and
      plaques on her left shoulder extending down her left arm after herpes zoster
      eruption. The histopathologil result showed lupus erythematosus. This phenomenon
      is best considered as a Koebner isomorphic response, although Wolf isotopic
      response has some clinical relevance as well. Koebner isomorphic and Wolf
      isotopic responses are discussed as related to this case. 

PMID- 22639954
TI  - Assessment of the specificity of Burkholderia and Pseudomonas qPCR assays for
      detection of these genera in soil using 454 pyrosequencing.
AB  - In this study, two highly specific quantitative PCR assays targeting the
      bacterial genera Burkholderia and Pseudomonas were developed and evaluated on
      soil samples. The primers were targeting different multivariate regions of the
      16S rRNA gene and designed to be compatible with quantitative PCR and the high
      throughput 454 pyrosequencing technique. The developed assays were validated
      using the standard methods. All tests with the new developed assays showed very
      high specificity. Pyrosequencing was used for direct analysis of the PCR product
      and applied as a specificity measurement of the primers. The Pseudomonas primers
      showed a 99% primer specificity, which covered 200 different Pseudomonas sequence
      clusters in 0.5 g of soil. In contrast to that the same approach using the genus
      specific Burkholderia primers showed only 8% primer specificity. This discrepancy
      in primer specificity between the normal procedures compared with pyrosequencing
      illustrates that the common validation procedures for quantitative PCR primers
      may be misleading. Our results exemplify the fact that current 16S RNA gene
      sequence databases might lack resolution within many taxonomic groups and
      emphasize the necessity for a standardized and functional primer validation
      protocol. A possible solution to this could be to supplement the normal
      verification of quantitative PCR assays with a pyrosequencing approach.

PMID- 22639956
TI  - Surgical treatment of atypical metastasis from renal cell carcinoma (RCC).
AB  - What's known on the subject? and What does the study add? The interest in
      metastatic renal cell carcinoma has increased in the last few years, mainly due
      to the advent of targeted therapies, but metastasectomy remains the sole therapy
      that can lead to a complete and durable regression, even if only in a minority of
      patients. The literature reports quite large series of metastasectomies for the
      most common sites of metastasis, e.g. lung, liver, bone, adrenal and brain,
      whereas little is known about the management of metastasis in 'atypical' sites.
      The prognosis of patients submitted to metastasectomy for a metastasis in an
      atypical site is equivalent to patients with lung metastasis. The characteristics
      of the primary tumour in these patients are not indicative, but atypical
      metastasis (AM) are often located in superficial sites and frequently associated
      with other metastases. So, physical examination should be included in all follow
      up regimens and a complete re-staging should be performed after the diagnosis of
      an AM. OBJECTIVE: * To review the clinical characteristics and oncological
      results in patients submitted to surgical removal of metastasis from renal cell
      carcinoma (RCC) in atypical sites (atypical metastasis [AM], i.e. metastasis in
      sites other than the chest, liver, bone, adrenal, brain, kidney, and lymph
      nodes), compared with patients submitted to metastasectomy due to a lung
      metastasis (LM). PATIENTS AND METHODS: * From an institutional database of ~1800
      patients surgically treated for a RCC, we retrospectively identified 37 cases
      that had undergone metastasectomy for AM and 57 operated for LM. *
      Clinicopathological features of the primary RCC and metastasis, and cancer
      specific survival (CSS) computed from the time of metastasectomy of patients with
      AM and LM, were compared. * A univariate and multivariable analysis applying a
      Cox regression model was used to evaluate CSS. RESULTS: * The patients with AM
      and LM were followed for an average of 40.8 and 50.7 months from metastasectomy,
      respectively (P= 0.372). * There were no significant differences in the
      characteristics of the primary tumour between patients with AM and LM. * In the
      cases with AM and LM the diagnosis was simultaneous with that of the primary
      tumour in 32.4% and 24.6%, (P= 0.40) respectively, and, when metachronous,
      occurred at an average delay of 53.4 and 44.3 months (P= 0.370). * More
      frequently in the cases with AM other metastases had been diagnosed in the
      previous medical history (35.2 vs 8.8%, P= 0.001) or simultaneously (48.6 vs
      8.8%, P= 0.001). * CSS from metastasectomy was affected by the synchronicity in
      diagnosis between metastasis and primary tumour, and by the simultaneous presence
      of other metastases, while the type of metastasis (AM vs LM) did not affect CSS.
      In fact, metastasectomy in AM was as effective as in LM. CONCLUSION: * AM are an
      exceptional presentation of metastatic RCC, but the role of surgery is similar to
      that of pulmonary metastasis. In these cases, metastasectomy is accepted as
      possible care, and in AM the CSS after metastasectomy is similar.

PMID- 22639955
TI  - Streptococcus pneumoniae serotype 19A in Latin America and the Caribbean: a
      systematic review and meta-analysis, 1990-2010.
AB  - BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are in the process of
      implementation in Latin America. Experience in developed countries has shown that
      they reduce the incidence of invasive and non-invasive disease. However, there is
      evidence that the introduction of PCVs in universal mass vaccination programs,
      combined with inappropriate and extensive use of antibiotics, could be associated
      to changes in non-PCV serotypes, including serotype 19A. We conducted a
      systematic review to determine the distribution of serotype 19A, burden of
      pneumococcal disease and antibiotic resistance in the region. METHODS: We
      performed a systematic review of serotype 19A data from observational and
      randomized clinical studies in the region, conducted between 1990 and 2010, for
      children under 6 years. Pooled prevalence estimates from surveillance activities
      with confidence intervals were calculated. RESULTS: We included 100 studies in 22
      countries and extracted data from 63. These data reported 19733 serotyped
      invasive pneumococcal isolates, 3.8% of which were serotype 19A. Serotype 19A
      isolates were responsible for 2.4% acute otitis media episodes, and accounted for
      4.1% and 4.4% of 4,380 nasopharyngeal isolates from healthy children and in
      hospital-based/sick children, respectively. This serotype was stable over the
      twenty years of surveillance in the region. A total of 53.7% Spn19A isolates from
      meningitis cases and only 14% from non meningitis were resistant to penicillin.
      CONCLUSIONS: Before widespread PCV implementation in this region, serotype 19A
      was responsible for a relatively small number of pneumococcal disease cases. With
      increased use of PCVs and a greater number of serotypes included, monitoring S.
      pneumoniae serotype distribution will be essential for understanding the
      epidemiology of pneumococcal disease.

PMID- 22639957
TI  - Cell division and endoreduplication play important roles in stem swelling of
      tuber mustard (Brassica juncea Coss. var. tumida Tsen et Lee).
AB  - We investigated spatio-temporal variations in cell division and the occurrence of
      endoreduplication in cells of tuber mustard stems during development. Cells in
      the stem had 8C nuclei (C represents DNA content of a two haploid genome), since
      it is an allotetraploid species derived from diploid Brassica rapa (AA) and B.
      nigra (BB), thus indicating the occurrence of endoreduplication. Additionally, we
      observed a dynamic change of cell ploidy in different regions of the swollen
      stems, with a decrease in 4C proportion in P4-1 and a sharp increase in 8C cells
      that became the dominant cell type (86.33% at most) in the inner pith cells.
      Furthermore, cDNAs of 14 cell cycle genes and four cell expansion genes were
      cloned and their spatial transcripts analysed in order to understand their roles
      in stem development. The expression of most cell cycle genes peaked in regions of
      the outer pith (P2 or P3), some genes regulating S/G2 and G2/M (BjCDKB1;2,
      BjCYCB1;1 and BjCYCB1;2) significantly decrease in P5 and P6, while G1/S
      regulators (BjE2Fa, BjE2Fb and BjE2Fc) showed a relative high expression level in
      the inner pith (P5) where cells were undergoing endoreduplication.
      Coincidentally, BjXTH1and BjXTH2 were exclusively expressed in the
      endoreduplicated cells. Our results suggest that cells of outer pith regions (P2
      and P3) mainly divide for cell proliferation, while cells of the inner pith
      expand through endoreduplication. Endoreduplication could trigger expression of
      BjXTH1 and BjXTH2 and thus function in cell expansion of the pith tissue.

PMID- 22639958
TI  - The converging and diverging characteristics of HIV-positive and HIV-negative gay
      men in the Australian Gay Community Periodic Surveys, 2000-2009.
AB  - To assess the changing health promotion needs of human immunodeficiency virus
      (HIV)-positive gay men in Australia, we analysed the social and behavioural
      characteristics of HIV-positive men in the Australian Gay Community Periodic
      Surveys. We looked at change over time in the characteristics of HIV-positive men
      (from 2000-2001 to 2008-2009) and compared HIV-positive men with their HIV
      negative peers within each time period. Multivariate logistic regression analysis
      was used to assess independent changes over time within each HIV status group. A
      total of 21,620 responses were included in the analyses; 10,537 in 2000-2001 and
      11,083 in 2008-2009. Between the two time periods, HIV-positive and HIV-negative
      men became more similar in the following areas: paid employment, sexual identity,
      number of male sex partners, the likelihood of having a regular male partner and
      having a seroconcordant regular male partner. The two groups diverged in these
      areas: age, ethnicity, educational level, social engagement with gay men, types
      of relationship with regular male partners, likelihood of unprotected anal
      intercourse with casual male partners and likelihood of HIV disclosure to casual
      male partners. Workforce participation and educational attainment have improved
      among HIV-positive gay men since 2000, but they still lag behind their HIV
      negative peers in these areas. Because HIV-positive men are an ageing cohort,
      support services will need to increasingly address issues of HIV, sexuality and
      ageing with HIV-positive men. The increase in unprotected anal intercourse and
      HIV disclosure with casual partners means that education and support services
      will increasingly need to address effective HIV disclosure and non-condom-based
      risk reduction strategies with both HIV-positive and HIV-negative gay men.

PMID- 22639959
TI  - The addition of the farnesyl transferase inhibitor, tipifarnib, to low dose
      cytarabine does not improve outcome for older patients with AML.
AB  - The AML16 trial evaluated the combination of the farnesyltransferase inhibitor,
      tipifarnib, and low dose cytarabine (LDAC) in older acute myeloid leukaemia (AML)
      patients in a 'Pick a Winner' design. The aim was to double remission rates
      compared to LDAC, with initial evaluation after 100 patients. Failure to improve
      remission would result in discontinuation. A total of 65 patients, median age 74
      years (range 62-86), were randomized. After reviewing the first 45 patients, the
      Data Monitoring Committee concluded that the overall aspirations would not be met
      and recommended closure. The addition of tipifarnib had no effect on response,
      toxicity or survival.

PMID- 22639960
TI  - Lucid dreaming: an age-dependent brain dissociation.
AB  - The current study focused on the distribution of lucid dreams in school children
      and young adults. The survey was conducted on a large sample of students aged 6
      19 years. Questions distinguished between past and current experience with lucid
      dreams. Results suggest that lucid dreaming is quite pronounced in young
      children, its incidence rate drops at about age 16 years. Increased lucidity was
      found in those attending higher level compared with lower level schools. Taking
      methodological issues into account, we feel confident to propose a link between
      the natural occurrence of lucid dreaming and brain maturation.

PMID- 22639961
TI  - Dissociating the two faces of selective memory retrieval.
AB  - Research in the past four decades has repeatedly shown that selective retrieval
      of some (non-target) memories can impair subsequent retrieval of other (target)
      information, a finding known as retrieval-induced forgetting. More recently,
      however, there is evidence that selective retrieval can both impair and enhance
      recall of related memories (K-H. T. Bauml & Samenieh, 2010). To identify possible
      experimental dissociations between the detrimental and the beneficial effects of
      memory retrieval, we examined retrieval dynamics in listwise directed forgetting,
      varying the delay between preceding non-target and subsequent target recall. When
      target recall immediately followed non-target recall, we replicated the prior
      work and found detrimental effects of memory retrieval on to-be-remembered items
      but beneficial effects on to-be-forgotten items. In contrast, when a delay was
      introduced between non-target and target recall, the detrimental effects were
      present but the beneficial effects were absent. The results demonstrate a first
      experimental dissociation between the two effects of memory retrieval. They are
      consistent with a recent two-factor account of the two faces of selective memory
      retrieval.

PMID- 22639962
TI  - Feasibility study of paclitaxel plus carboplatin in patients with endometrial
      cancer: a Japan Kanto Tumor Board study (JKTB trial).
AB  - AIM: The optimal chemotherapy regimen for patients with endometrial cancer has
      not been established. We assessed the feasibility of paclitaxel plus carboplatin
      (TC) for postoperative chemotherapy in patients with endometrial cancer. MATERIAL
      AND METHODS: Patients with newly diagnosed endometrial cancer received TC
      (paclitaxel 180 mg/m(2) , carboplatin AUC6 mg/mL/min) every three weeks.
      Treatment was continued until disease progression or completion of six cycles.
      Toxicities were evaluated every cycle according to NCI-CTCAE version 3.0.
      RESULTS: Sixty patients were registered from December 2005 through November 2006.
      Forty-four of 60 (73.3%) cases completed all of the planned six cycles. Grades 3
      and 4 hematologic toxicities were observed as follows: leukopenia (61.7%),
      neutropenia (95.0%), anemia (21.7%), and thrombocytopenia (5.0%). There were six
      patients who dropped out from the protocol by neutropenia. Grade 3 non
      hematologic toxicities were observed as follows: nausea (3.3%), vomiting (1.7%),
      neuropathy (5.0%), myalgia (6.7%) and constipation (1.7%). No grade 4 non
      hematologic toxicity was observed. CONCLUSION: This TC regimen is feasible for
      endometrial cancer patients.

PMID- 22639963
TI  - Evaluation of performance of co crystals of mefloquine hydrochloride in tablet
      dosage form.
AB  - OBJECTIVE: The objective of present investigation was to evaluate performance of
      cocrystals of Mefloquine Hydrochloride (MFL) in tablet dosage form. Our previous
      investigation showed significant effect of cocrystal formers on improving the
      solubility and dissolution rate of Mefloquine hydrochloride by cocrystallization
      method when prepared by solution cocrystallization method. MATERIALS AND METHODS:
      Prepared cocrystals of MFL with different ratio of cocrystal formers were
      incorporated in tablet dosage form and evaluated for micrometric properties, drug
      content, hardness, disintegration test, vitro dissolution studies and stability
      studies. Performance was compared with laboratory prepared tablet of MFL 250 mg.
      RESULTS: The considerable improvement in the dissolution rate was observed in
      case of cocrystals based tablets than pure MFL tablets. DISCUSSION AND
      CONCLUSION: So we can incorporate cocrystals in tablet dosage form to enhance in
      vitro and in vivo performance. To the best of our knowledge, this is the first
      report, cocrystals has been evaluated in tablet dosage form.

PMID- 22639964
TI  - Predictors of condom use and refusal among the population of Free State province
      in South Africa.
AB  - BACKGROUND: This study investigated the extent and predictors of condom use and
      condom refusal in the Free State province in South Africa. METHODS: Through a
      household survey conducted in the Free Sate province of South Africa, 5,837
      adults were interviewed. Univariate and multivariate survey logistic regressions
      and classification trees (CT) were used for analysing two response variables
      'ever used condom' and 'ever refused condom'. RESULTS: Eighty-three per cent of
      the respondents had ever used condoms, of which 38% always used them; 61% used
      them during the last sexual intercourse and 9% had ever refused to use them. The
      univariate logistic regression models and CT analysis indicated that a strong
      predictor of condom use was its perceived need. In the CT analysis, this variable
      was followed in importance by 'knowledge of correct use of condom', condom
      availability, young age, being single and higher education. 'Perceived need' for
      condoms did not remain significant in the multivariate analysis after controlling
      for other variables. The strongest predictor of condom refusal, as shown by the
      CT, was shame associated with condoms followed by the presence of sexual risk
      behaviour, knowing one's HIV status, older age and lacking knowledge of condoms
      (i.e., ability to prevent sexually transmitted diseases and pregnancy,
      availability, correct and consistent use and existence of female condoms). In the
      multivariate logistic regression, age was not significant for condom refusal
      while affordability and perceived need were additional significant variables.
      CONCLUSIONS: The use of complementary modelling techniques such as CT in addition
      to logistic regressions adds to a better understanding of condom use and refusal.
      Further improvement in correct and consistent use of condoms will require
      targeted interventions. In addition to existing social marketing campaigns,
      tailored approaches should focus on establishing the perceived need for condom
      use and improving skills for correct use. They should also incorporate
      interventions to reduce the shame associated with condoms and individual
      counselling of those likely to refuse condoms.

PMID- 22639965
TI  - Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin-like
      protein.
AB  - Mutations in Leucine-rich repeat kinase 2 (LRRK2) are the leading causes of
      genetically inherited Parkinson's disease (PD) identified so far. The underlying
      mechanism whereby missense alterations in LRRK2 initiate neurodegeneration
      remains largely unclear. Mitochondrial dysfunction has been recognized to
      contribute to the pathogenesis of both sporadic and familial PD. The pathogenic
      gain-of-function mutant form of LRRK2, LRRK2 G2019S, is associated with elevated
      kinase activity and PD. Here we show that LRRK2 G2019S can cause defects in the
      morphology and dynamics of mitochondria in cortical neurons. In neurons,
      endogenous LRRK2 and the mitochondrial fission factor Dynamin like protein 1
      (DLP1) interact with and partially co-localize with each other. DLP1 plays an
      essential role in LRRK2-induced mitochondrial fission. In support of this,
      expression of LRRK2 leads to the translocation of DLP1 from the cytosol to the
      mitochondria and knockdown of DLP1 expression inhibits LRRK2-induced
      mitochondrial fission. In addition, co-expression of LRRK2 and DLP1 induces
      mitochondrial clearance. Furthermore, we have found that expression of LRRK2
      leads to increased reactive oxygen species levels in cells. Taken together, our
      results provide insights into the pathobiology of LRRK2 and suggest that LRRK2
      G2019S may induce neuronal dysfunction or cell death by disturbing normal
      mitochondrial fission/fusion dynamics and function.

PMID- 22639966
TI  - Therapeutic effects of radix dipsaci, pyrola herb, and Cynomorium songaricum on
      bone metabolism of ovariectomized rats.
AB  - BACKGROUND: The objective of this study was to evaluate the effects of herbal
      medicines, such as Radix Dipsaci (RDD), Pyrola Herb (PHD), and Cynomorium
      songaricum decoction (CSD), on osteoporotic rats induced by ovariectomy (OVX).
      METHODS: OVX or sham operations were performed on 69 virgin Wistar rats that were
      divided into six groups: sham (sham, n = 12), OVX control group (OVX, n = 12),
      and OVX rats with treatments (diethylstilbestrol, E2, n = 12; RDD, n = 11, PHD, n
      = 11, and CSD, n = 11). Non-surgical rats served as normal control (NC, n = 12).
      The treatments began four weeks after surgery and lasted for 12 weeks. Bone mass
      and bone turnover were analyzed by histomorphometry. Levels of protein expression
      and mRNA of OPG and RANKL in osteoblasts (OB) and bone marrow stromal cells
      (bMSC) were evaluated by immunohistochemistry and in situ hybridization. RESULTS:
      Compared to NC and sham rats, trabecular bone formation was significantly reduced
      in OVX rats, but restored in E2-treated rats. Treatment with either RDD or PHD
      enhanced trabecular bone formation remarkably. No significant change of bone
      formation was observed in CSD-treated rats. OPG expression of protein and mRNA
      was reduced significantly in OB and bMSC of OVX control rats. RANKL expression of
      protein and mRNA was increased significantly in OB and bMSC of OVX control rats.
      These effects were substantially reversed (increased in OPG and decreased in
      RANKL) by treatment with E2, RDD, or PHD in OB and bMSC of OVX rats. No
      significant changes in either OPG or RANKL expression were observed in OB and
      bMSC of OVX rats treated with CSD. CONCLUSIONS: Our study showed that RDD and PHD
      increased bone formation by stimulating overexpression of OPG and downregulation
      of RANKL in OB and bMSC. This suggests that RDD and PHD may be used as
      alternative therapeutic agents for postmenopausal osteoporosis.

PMID- 22639967
TI  - Dopamine-assisted rapid fabrication of nanoscale protein arrays by colloidal
      lithography.
AB  - The development of cost-effective methodologies for the precise nanometer-scale
      positioning of biomolecules permits the low-cost production of various
      biofunctional devices for a range of biomedical and nanotechnological
      applications. By combining colloidal lithography and the mussel-inspired
      multifunctional polydopamine coating, we present a novel parallel benchtop method
      that allows rapid nanoscale patterning of proteins without the need for
      electrically powered equipment in the fabrication process. The PDA-immobilized
      binary nanopattern consisting of BSA surrounded by PLL-g-PEG is fabricated over a
      large area, and the integrity of the pattern is confirmed using AFM and FM.

PMID- 22639968
TI  - Hailey-Hailey disease and tight junctions: Claudins 1 and 4 are regulated by
      ATP2C1 gene encoding Ca(2+) /Mn(2+)  ATPase SPCA1 in cultured keratinocytes.
AB  - Mutations in the ATP2C1 gene encoding Ca(2+) /Mn(2+)  ATPase SPCA1 cause Hailey
      Hailey disease (HHD, OMIM 16960). HHD is characterized by epidermal acantholysis.
      We attempted to model HHD using normal keratinocytes, in which the SPCA1 mRNA was
      down-regulated with the small inhibitory RNA (siRNA) method. SiRNA inhibition
      significantly down-regulated the SPCA1 mRNA, as demonstrated by qPCR, and
      decreased the SPCA1 protein beyond detectable level, as shown by Western
      analysis. The expression of selected desmosomal, adherens and tight junction (TJ)
      proteins was then studied in the SPCA1-deficient and control keratinocytes
      cultured in low (0.06 mm) or high (1.2 mm) calcium concentration. The mRNA and
      protein levels of most TJ components were up-regulated in non-treated control
      keratinocyte cultures upon switch from low to high calcium concentration. In
      contrast, SPCA1-deficient keratinocytes displayed high levels of TJ proteins
      claudins 1 and 4 even in low calcium. ZO-1 did not, however, follow similar
      expression patterns. Protein levels of occludin, beta-catenin, E-cadherin,
      desmoplakin, desmogleins 1-3, desmocollin 2/desmocollin 3 and plakoglobin did not
      show marked changes in SPCA1-deficient keratinocytes. Indirect immunofluorescence
      labelling revealed delayed translocation of desmoplakin and desmoglein 3 in
      desmosomes and increased intracellular pools of TJ and desmosomal components in
      SPCA1-inhibited keratinocytes. The results show that SPCA1 regulates the levels
      of claudins 1 and 4, but does not affect desmosomal protein levels, indicating
      that TJ proteins are differently regulated. The results also suggest a potential
      role for claudins in HHD.

PMID- 22639969
TI  - Mass-resolved infrared spectroscopy of complexes without chromophore by
      nonresonant femtosecond ionization detection.
AB  - Mass-resolved excitation spectroscopic techniques are usually limited to systems
      with a chromophore, that is, a functional group with electronic transitions in
      the Vis/UV, with lifetimes from hundreds of picoseconds to some microseconds. In
      this paper, we expand such techniques to any system, by using a combination of
      nanosecond IR pulses with nonresonant ionization with 800 nm femtosecond laser
      pulses. Furthermore, we demonstrate that the technique can achieve conformational
      specificity introducing an additional nanosecond IR laser. As a proof-of
      principle, we apply the technique to the study of phenol(H(2)O)(1),
      propofol(H(2)O)(1) gamma-butyrolactone(H(2)O)(n), n = 1-3, and (H(2)O)(2)
      complexes. While monohydrated phenol and propofol clusters permit a direct
      comparison with a well-studied system including an aromatic chromophore, gamma
      butyrolactone is a cyclic nonaromatic molecule, whose mass-resolved spectroscopy
      cannot be tackled by conventional techniques. Finally, we further demonstrate the
      potential of the technique by obtaining the first mass-resolved IR spectrum of
      the neutral water dimer, a nice example of a system whose ionization-based
      detection had not been possible to date.

PMID- 22639971
TI  - Investigation of the concurrent emergence of Salmonella enteritidis in humans and
      poultry in British Columbia, Canada, 2008-2010.
AB  - An increase in the rate of human infections with Salmonella enteritidis (SE)
      occurred between 2007 and 2010 in British Columbia (BC). During the same time
      period, an increase in SE from poultry-sourced isolates and increased clinical
      severity in poultry were also observed in BC. This article describes a multi
      sectoral collaboration during a 3-year investigation, and the actions taken by
      public health and animal health professionals. Human cases were interviewed,
      clusters were investigated, and a case-control study was conducted. Environmental
      investigations were conducted in food service establishments (FSE). Suspect foods
      were tested. Laboratory data from poultry-sourced isolates were analysed. Five
      hundred and eighty-four human cases of SE with the same pulsed-field gel
      electrophoresis pattern were identified between May 2008 and August 2010. Seventy
      three percentage of cases reported consumption of eggs. The odds of egg
      consumption were 2.4 times higher for cases than controls. Implicated FSE were
      found to use ungraded eggs, which had been distributed illegally. Investigation
      suggested that there were multiple suppliers of these eggs. Collaboration between
      public health and animal health professionals led to data sharing, improved
      understanding of SE, engagement with the poultry industry and public
      communication. Multi-disciplinary, multi-sectoral and multi-pronged
      investigations are recommended to identify the likely source of illness in large,
      protracted foodborne outbreaks caused by commonly consumed foods.

PMID- 22639972
TI  - Effects on bone by the light/dark cycle and chronic treatment with melatonin
      and/or hormone replacement therapy in intact female mice.
AB  - In this study, the effects of the light/dark cycle, hormone replacement therapy
      (HRT), and nocturnal melatonin supplementation on osteogenic markers and serum
      melatonin levels were examined in a blind mouse model (MMTV-Neu transgenic mice).
      Melatonin levels in this mouse strain (FVB/N) with retinal degeneration (rd-/-)
      fluctuate in a diurnal manner, suggesting that these mice, although blind, still
      perceive light. Real-time RT-PCR analyses demonstrated that Runx2, Bmp2, Bmp6,
      Bglap, and Per2 mRNA levels coincide with melatonin levels. The effect of chronic
      HRT (0.5 mg 17beta-estradiol + 50 mg progesterone in 1800 kcal of diet) alone and
      in combination with melatonin (15 mg/L drinking water) on bone quality and
      density was also assessed by histomorphometry and microcomputed tomography,
      respectively. Bone density was significantly increased (P < 0.05) after 1 yr of
      treatment with the individual therapies, HRT (22% increase) and nocturnal
      melatonin (20% increase) compared to control. Hormone replacement therapy alone
      also increased surface bone, decreased trabecular space, and decreased the number
      of osteoclasts without affecting osteoblast numbers compared to the control group
      (P < 0.05). Chronic HRT + melatonin therapy did not significantly increase bone
      density, even though this combination significantly increased Bglap mRNA levels.
      These data suggest that the endogenous melatonin rhythm modulates markers
      important to bone physiology. Hormone replacement therapy with or without
      nocturnal melatonin in cycling mice produces unique effects on bone markers and
      bone density. The effects of these therapies alone and combined may improve bone
      health in women in perimenopause and with low nocturnal melatonin levels from too
      little sleep, too much light, or age.

PMID- 22639973
TI  - FFA1-selective agonistic activity based on docking simulation using FFA1 and
      GPR120 homology models.
AB  - BACKGROUND AND PURPOSE The free fatty acid FFA1 receptor and GPR120 are GPCRs
      whose endogenous ligands are medium- and long-chain FFAs, and they are important
      in regulating insulin and GLP-1 secretion respectively. Given that the ligands of
      FFA1 receptor and GPR120 have similar properties, selective pharmacological tools
      are required to study their functions further. EXPERIMENTAL APPROACH We used a
      docking simulation approach using homology models for each receptor. Biological
      activity was assessed by phosphorylation of ERK and elevation of intracellular
      calcium ([Ca(2+) ]i ) in cells transfected with FFA1 receptor or GPR120. Insulin
      secretion from murine pancreatic beta cells (MIN6) was also measured. KEY RESULTS
      Calculated hydrogen bonding energies between a series of synthetic carboxylic
      acid compounds and the homology models of the FFA1 receptor and GPR120, using
      docking simulations, correlated well with the effects of the compounds on ERK
      phosphorylation in transfected cells (R(2) = 0.65 for FFA1 receptor and 0.76 for
      GPR120). NCG75, the compound with the highest predicted selectivity for FFA1
      receptors from this structure-activity relationship analysis, activated ERK and
      increased [Ca(2+) ]i as potently as the known FFA1 receptor-selective agonist,
      Compound 1. Site-directed mutagenesis analysis based on the docking simulation
      showed that different amino acid residues were important for the recognition and
      activation by FFA1 receptor agonists. Moreover, NCG75 strongly induced ERK and
      [Ca(2+) ]i responses, and promoted insulin secretion from MIN6 cells, which
      express endogenous FFA1 receptors. CONCLUSION AND IMPLICATIONS A docking
      simulation approach using FFA1 receptor and GPR120 homology models could be
      useful in predicting FFA1 receptor-selective agonists.

PMID- 22639974
TI  - Is the use of cholesterol in mortality risk algorithms in clinical guidelines
      valid? Ten years prospective data from the Norwegian HUNT 2 study.

PMID- 22639975
TI  - Transposon mutagenesis of the anaerobic commensal,  Bacteroides fragilis, using
      the EZ::TN5 transposome.
AB  - Genetic analysis of Bacteroides fragilis (BF) is hindered because of the lack of
      efficient transposon mutagenesis methods. Here, we describe a simple method for
      transposon mutagenesis using EZ::TN5, a commercially available system that we
      optimized for use in BF638R. The modified EZ::TN5 transposon contains an
      Escherichia coli conditional origin of replication, a kanamycin resistance gene
      for E. coli, an erythromycin resistance gene for BF , and 19 basepair transposase
      recognition sequences on either ends. Electroporation of the transposome
      (transposon-transposase complex) into BF638R yielded 3.2 +/- 0.35 * 10(3) CFU
      MUg(-1) of transposon DNA. Modification of the transposon by the BF638R
      restriction/modification system increased transposition efficiency sixfold.
      Electroporation of the EZ::TN5 transposome results in a single-copy insertion of
      the transposon evenly distributed across the genome of BF638R and can be used to
      construct a BF638R transposon library. The transposon was also effective in
      mutating a BF clinical isolate and a strain of the related species, Bacteroides
      thetaiotaomicron. The EZ::TN5-based mutagenesis described here is more efficient
      than other transposon mutagenesis approaches previously reported for BF.

PMID- 22639976
TI  - Treatment of pediatric molluscum contagiosum with 10% potassium hydroxide
      solution.
AB  - BACKGROUND: Molluscum contagiosum (MC) is a common cutaneous viral infection of
      the skin that is frequently seen in children. Although lesions can resolve
      spontaneously, treatment is mandatory because of the psychological effect of
      widespread lesions in children. Potassium hydroxide (KOH) is a strong alkali that
      has been used by dermatologists for a long time in identifying the fungal
      infections from skin scrapings. AIMS: We evaluated 40 children with MC for the
      safety and efficacy of treatment with topical 10% KOH aqueous solution. METHODS:
      Parents were instructed to apply a 10% KOH aqueous solution, twice daily, with a
      cotton stick to all lesions. Treatment was continued till the lesions showed
      signs of inflammation or superficial ulceration. Assessments of response and side
      effects were performed at the end of week 2, week 4, week 8 and week 12. RESULTS:
      We found complete clearance of lesions in 37 (92.5%) patients receiving topical
      10%KOH solution after a mean period of four weeks. Three children dropped out of
      the study; two children reported severe stinging of the lesions and discontinued
      the treatment; the other patient developed hypopigmentation during the treatment.
      Local side effects were observed in 12 children (32.4%). CONCLUSION: Even though
      10% KOH solution is associated with some local side effects, it is a safe,
      effective, inexpensive and noninvasive alternative treatment of MC in children.

PMID- 22639977
TI  - Association between polymorphisms in the adiponectin gene and cardiovascular
      disease: a meta-analysis.
AB  - BACKGROUND: Previous studies have examined the associations between polymorphisms
      of adiponectin gene (ADIPOQ) and cardiovascular disease (CVD), but those studies
      have been inconclusive. The aim of this study was to access the relationship
      between three single nucleotide polymorphisms (SNPs), +45 T > G (rs2241766), +276
      G > T (rs1501299) and -11377 C > G (rs266729) in ADIPOQ and CVD. METHODS: A
      comprehensive search was conducted to identify all studies on the association of
      ADIPOQ gene polymorphisms with CVD risk. The fixed and random effect pooled
      measures (i.e. odds ratio (OR) and 95% confidence interval (CI)) were calculated
      in the meta-analysis. Heterogeneity among studies was evaluated using Q test and
      the I2. Publication bias was estimated using modified Egger's linear regression
      test. RESULTS: Thirty-seven studies concerning the associations between the three
      polymorphisms of ADIPOQ gene and CVD risk were enrolled in this meta-analysis,
      including 6,398 cases and 10,829 controls for rs2241766, 8,392 cases and 18,730
      controls for rs1501299 and 7,835 cases and 14,023 controls for rs266729. The
      three SNPs were significantly associated with CVD, yielding pooled ORs of 1.22
      (95%CI: 1.07, 1.39; P = 0.004), 0.90 (95%CI: 0.83, 0.97; P = 0.007) and
      1.09(95%CI: 1.01, 1.17; P = 0.032) for rs2241766, rs1501299 and rs266729,
      respectively. Rs2241766 and rs1501299 were significantly associated with coronary
      heart disease (CHD), yielding pooled ORs of 1.29 (95%CI: 1.09, 1.52; P = 0.004)
      and 0.89 (95%CI: 0.81, 0.99; P = 0.025), respectively. The pooled OR for rs266729
      and CHD was 1.09 (95%CI: 0.99, 1.19; P = 0.090). Significant between-study
      heterogeneity was found in our meta-analysis. Evidence of publication bias was
      observed in the meta-analysis. CONCLUSIONS: The present meta-analysis showed that
      the associations between rs2241766, rs1501299 and rs266729 in the ADIPOQ and CVD
      were significant but weak. High quality studies are still needed to confirm the
      associations, especially for rs2241766.

PMID- 22639978
TI  - Short term stability of verbal memory impairment in mild cognitive impairment and
      Alzheimer's disease measured using the International Shopping List Test.
AB  - There is a need for culture neutral neuropsychological instruments. The
      International Shopping List Test (ISLT) is sensitive to memory impairment in
      Alzheimer's disease (AD) in different cultural groups, although its sensitivity
      to mild cognitive impairment (MCI) and ability to be given repeatedly at short
      retest intervals is unknown. Performance on the ISLT was compared between groups
      of healthy adults, MCI, and AD from the Australian Imaging Biomarkers and
      Lifestyle study of ageing. Subjects were assessed four times in three months. In
      each group, the ISLT performance measures had high test-retest reliability, and
      group means remained stable over time. There was no difference between groups on
      within-subject variability. These data suggest that in English-speaking samples,
      the ISLT is sensitive to MCI and can be given repeatedly in order to assess
      change in memory.

PMID- 22639980
TI  - Robotic surgery and standard laparoscopy: a surgical hybrid technique for use in
      colorectal endometriosis.
AB  - AIM: The aim of our work was to assess the feasibility and possible benefits of a
      novel hybrid surgical technique in rectosigmoidal resection in patients with
      bowel endometriosis. MATERIAL AND METHODS: A total of seven symptomatic and
      infertile women with severe bowel endometriosis underwent segmental bowel
      resection using the da Vinci surgical system and conventional laparoscopy.
      Statistical analysis was performed by Friedman test for non-parametric multiple
      comparisons. RESULTS: The surgical procedure has a determined short mean
      operative time (210min) and short postoperative hospitalization (five days). In
      100% of patients, the resected area showed disease-free margins. Follow-up,
      carried out at three, six and 12months after operation, showed a regression of
      painful symptoms in all operated patients (100%). Two patients (28.6%)
      aged>=35years eventually had natural pregnancies. CONCLUSION: To the best of our
      knowledge, this report is the first concerning the use of a hybrid technique for
      intestinal resection in severe endometriosis, and comparing our data with that in
      the literature, its methodological and clinical advantages are evident. Moreover,
      the complete removal of endometriotic implants seems to offer good results in
      terms of postoperative fertility, although the study data do not allow us to draw
      definitive conclusions on the management of fertility.

PMID- 22639979
TI  - Temporal analysis of vascular smooth muscle cell elasticity and adhesion reveals
      oscillation waveforms that differ with aging.
AB  - A spectral analysis approach was developed for detailed study of time-resolved,
      dynamic changes in vascular smooth muscle cell (VSMC) elasticity and adhesion to
      identify differences in VSMC from young and aged monkeys. Atomic force microscopy
      (AFM) was used to measure Young's modulus of elasticity and adhesion as assessed
      by fibronectin (FN) or anti-beta 1 integrin interaction with the VSMC surface.
      Measurements demonstrated that VSMC cells from old vs. young monkeys had
      increased elasticity (21.6 kPa vs. 3.5 kPa or a 612% increase in elastic modulus)
      and adhesion (86 pN vs. 43 pN or a 200% increase in unbinding force). Spectral
      analysis identified three major frequency components in the temporal oscillation
      patterns for elasticity (ranging from 1.7 * 10(-3) to 1.9 * 10(-2) Hz in old and
      8.4 * 10(-4) to 1.5 * 10(-2) Hz in young) and showed that the amplitude of
      oscillation was larger (P < 0.05) in old than in young at all frequencies. It was
      also observed that patterns of oscillation in the adhesion data were similar to
      the elasticity waveforms. Cell stiffness was reduced and the oscillations were
      inhibited by treatment with cytochalasin D, ML7 or blebbistatin indicating the
      involvement of actin-myosin-driven processes. In conclusion, these data
      demonstrate the efficacy of time-resolved analysis of AFM cell elasticity and
      adhesion measurements and that it provides a uniquely sensitive method to detect
      real-time functional differences in biomechanical and adhesive properties of
      cells. The oscillatory behavior suggests that mechanisms governing elasticity and
      adhesion are coupled and affected differentially during aging, which may link
      these events to changes in vascular stiffness.

PMID- 22639981
TI  - Functional expression and characterisation of membrane transport proteins.
AB  - Membrane transporters set the framework organising the complexity of plant
      metabolism in cells, tissues and organisms. Their substrate specificity and
      controlled activity in different cells is a crucial part for plant metabolism to
      run pathways in concert. Transport proteins catalyse the uptake and exchange of
      ions, substrates, intermediates, products and cofactors across membranes. Given
      the large number of metabolites, a wide spectrum of transporters is required. The
      vast majority of in silico annotated membrane transporters in plant genomes,
      however, has not yet been functionally characterised. Hence, to understand the
      metabolic network as a whole, it is important to understand how transporters
      connect and control the metabolic pathways of plant cells. Heterologous
      expression and in vitro activity studies of recombinant transport proteins have
      highly improved their functional analysis in the last two decades. This review
      provides a comprehensive overview of the recent advances in membrane protein
      expression and functional characterisation using various host systems and
      transport assays. 

PMID- 22639982
TI  - Under-recognized complications in patients with paroxysmal nocturnal
      haemoglobinuria: raised pulmonary pressure and reduced right ventricular
      function.
AB  - Pulmonary hypertension is becoming a recognized complication of the hereditary
      and acquired haemolytic anaemias, associated with a poor prognosis. Recently we
      reported that patients with paroxysmal nocturnal haemoglobinuria (PNH) have high
      levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker
      associated with both right and left ventricular dysfunction and cardiac
      dysfunction. In the current study we evaluated a cohort of patients (N = 29) with
      haemolytic PNH for elevated pulmonary artery systolic pressure and cardiac
      function by Doppler-echocardiography. Of the 29 patients, eight were further
      studied using cardiac magnetic resonance imaging (MRI), as well as two additional
      patients (number of patients studied using cardiac MRI = 10). Plasma from the
      first cohort (N = 29) demonstrated intravascular haemolysis associated with a 12
      fold increase in median nitric oxide (NO) consumption when compared with healthy
      volunteers (P < 0.001). Doppler echocardiography demonstrated normal left
      ventricular function and elevated pulmonary artery systolic pressure in 41% of
      patients. Cardiac MRI from the second cohort (N = 10) demonstrated depressed
      right ventricular function in 80% of PNH patients tested, and 60% had findings
      suggestive of subclinical small pulmonary emboli. Together, these data suggest a
      high prevalence of haemolysis-associated NO scavenging, Doppler-estimated
      systolic pulmonary hypertension, and depressed right ventricular function in
      patients with PNH.

PMID- 22639983
TI  - Unraveling the electronic structures of low-valent naphthalene and anthracene
      iron complexes: X-ray, spectroscopic, and density functional theory studies.
AB  - Naphthalene and anthracene transition metalates are potent reagents, but their
      electronic structures have remained poorly explored. A study of four Cp*
      substituted iron complexes (Cp* = pentamethylcyclopentadienyl) now gives rare
      insight into the bonding features of such species. The highly oxygen- and water
      sensitive compounds [K(18-crown-6){Cp*Fe(eta(4)-C(10)H(8))}] (K1), [K(18-crown
      6){Cp*Fe(eta(4)-C(14)H(10))}] (K2), [Cp*Fe(eta(4)-C(10)H(8))] (1), and
      [Cp*Fe(eta(4)-C(14)H(10))] (2) were synthesized and characterized by NMR, UV-vis,
      and (57)Fe Mossbauer spectroscopy. The paramagnetic complexes 1 and 2 were
      additionally characterized by electron paramagnetic resonance (EPR) spectroscopy
      and magnetic susceptibility measurements. The molecular structures of complexes
      K1, K2, and 2 were determined by single-crystal X-ray crystallography. Cyclic
      voltammetry of 1 and 2 and spectroelectrochemical experiments revealed the redox
      properties of these complexes, which are reversibly reduced to the monoanions
      [Cp*Fe(eta(4)-C(10)H(8))](-) (1(-)) and [Cp*Fe(eta(4)-C(14)H(10))](-) (2(-)) and
      reversibly oxidized to the cations [Cp*Fe(eta(6)-C(10)H(8))](+) (1(+)) and
      [Cp*Fe(eta(6)-C(14)H(10))](+) (2(+)). Reduced orbital charges and spin densities
      of the naphthalene complexes 1(-/0/+) and the anthracene derivatives 2(-/0/+)
      were obtained by density functional theory (DFT) methods. Analysis of these data
      suggests that the electronic structures of the anions 1(-) and 2(-) are best
      represented by low-spin Fe(II) ions coordinated by anionic Cp* and dianionic
      naphthalene and anthracene ligands. The electronic structures of the neutral
      complexes 1 and 2 may be described by a superposition of two resonance
      configurations which, on the one hand, involve a low-spin Fe(I) ion coordinated
      by the neutral naphthalene or anthracene ligand L, and, on the other hand, a low
      spin Fe(II) ion coordinated to a ligand radical L(*-). Our study thus reveals the
      redox noninnocent character of the naphthalene and anthracene ligands, which
      effectively stabilize the iron atoms in a low formal, but significantly higher
      spectroscopic oxidation state.

PMID- 22639984
TI  - Functional differences between ATP-gated human and rat P2X3 receptors are caused
      by critical residues of the intracellular C-terminal domain.
AB  - ATP-activated P2X3 receptors of sensory ganglion neurons contribute to pain
      transduction and are involved in chronic pain signaling. Although highly
      homologous (97%) in rat and human species, it is unclear whether P2X3 receptors
      have identical function. Studying human and rat P2X3 receptors expressed in patch
      clamped human embryonic kidney (HEK) cells, we investigated the role of non
      conserved tyrosine residues in the C-terminal domain (rat tyrosine-393 and human
      tyrosine-376) as key determinants of receptor function. In comparison with rat
      P2X3 receptors, human P2X3 receptors were more expressed and produced larger
      responses with slower desensitization and faster recovery. In general,
      desensitization was closely related to peak current amplitude for rat and human
      receptors. Downsizing human receptor expression to the same level of the rat one
      still yielded larger responses retaining slower desensitization and faster
      recovery. Mutating phenylalanine-376 into tyrosine in the rat receptor did not
      change current amplitude; yet, it retarded desensitization onset, demonstrating
      how this residue was important to functionally link these two receptor states.
      Conversely, removing tyrosine from position 376 strongly down-regulated human
      receptor function. The different topology of tyrosine residues in the C-terminal
      domain has contrasting functional consequences and is sufficient to account for
      species-specific properties of this pain-transducing channel.

PMID- 22639985
TI  - Dissolution rate enhancement, in vitro evaluation and investigation of drug
      release kinetics of chloramphenicol and sulphamethoxazole solid dispersions.
AB  - Formulation of solid dispersions is one of the effective methods to increase the
      rate of solubilization and dissolution of poorly soluble drugs. Solid dispersions
      of chloramphenicol (CP) and sulphamethoxazole (SX) as model drugs were prepared
      by melt fusion method using polyethylene glycol 8000 (PEG 8000) as an inert
      carrier. The dissolution rate of CP and SX were rapid from solid dispersions with
      low drug and high polymer content. Characterization was performed using fourier
      transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC)
      and scanning electron microscopy (SEM). FTIR analysis for the solid dispersions
      of CP and SX showed that there was no interaction between PEG 8000 and the drugs.
      Hyper-DSC studies revealed that CP and SX were converted into an amorphous form
      when formulated as solid dispersion in PEG 8000. Mathematical analysis of the
      release kinetics demonstrated that drug release from the various formulations
      followed different mechanisms. Permeability studies demonstrated that both CP and
      SX when formulated as solid dispersions showed enhanced permeability across Caco
      2 cells and CP can be classified as well-absorbed compound when formulated as
      solid dispersions.

PMID- 22639986
TI  - Prospective prediction of viral suppression and immune response nine months after
      ART initiation in Seattle, WA.
AB  - Knowing at antiretroviral therapy (ART) initiation which patients might be at
      greatest risk for failure to achieve viral suppression would enable providers to
      target patients most in need and tailor their care appropriately. This study
      involved multilevel modeling of data from a randomized controlled trial among
      outpatients in Seattle, WA, USA. The 224 participants initiating or switching ART
      at baseline were 24% female, 34% heterosexual, and 47% Caucasian. Of 24 baseline
      demographic and psychosocial patient-level variables modeled in separate
      generalized estimating equations, only employment predicted changes in HIV-1 RNA
      viral load or CD4 lymphocyte count over the course of the 9-month trial. Although
      the findings require replication, they suggest adherence support strategies
      should emphasize close monitoring and support for all patients initiating ART.

PMID- 22639987
TI  - Supporting African refugees in Canada: insights from a support intervention.
AB  - Although evidence suggests the importance of social support for refugees, this
      knowledge has not been invoked to systematically develop culturally congruent
      support interventions that help refugees adapt to life in receiving countries.
      The objective of this study was to design and pilot test a culturally congruent
      intervention that meets the support needs and preferences of two ethno-culturally
      distinct refugee groups. Support was delivered to Somali and Sudanese refugees (n
      = 58), by trained peer and professional facilitators. Face-to-face groups
      comprised of refugees, matched by gender and ethnicity, were created to enhance
      the depleted social networks of Somali and Sudanese refugees. Each peer support
      group met bi-weekly for a face-to-face session for 12 weeks. Peer facilitators
      delivered supplementary one-to-one support via the telephone. The ingredients of
      the support intervention included: (i) peer facilitators and professionals; (ii)
      provision of information, affirmation and emotional support; and (iii)
      accessibility (e.g. childcare, transportation). The study employed a qualitative
      participatory research design. Data collected for the study included (i) in-depth
      pre-intervention interviews with potential support group participants in 2008
      2009 to assess intervention preferences; (ii) fieldnotes by peer and professional
      facilitators during the intervention in 2009-10; (iii) post-intervention group
      interviews with support group participants in 2010; and (iv) in-depth interviews
      with peer and professional helpers in 2010. A major perceived benefit of the
      support programme was connecting with people from African refugee participants'
      cultural communities. Participants appreciated the gender and culture-specific
      groups. Following the social support intervention, refugees reported increased
      social integration, decreased loneliness and expanded coping repertoire.

PMID- 22639988
TI  - The Do-Well study: protocol for a randomised controlled trial, economic and
      qualitative process evaluations of domiciliary welfare rights advice for socio
      economically disadvantaged older people recruited via primary health care.
AB  - BACKGROUND: Older people in poor health are more likely to need extra money, aids
      and adaptations to allow them to remain independent and cope with ill health, yet
      in the UK many do not claim the welfare benefits to which they are entitled.
      Welfare rights advice interventions lead to greater welfare income, but have not
      been rigorously evaluated for health benefits. This study will evaluate the
      effects on health and well-being of a domiciliary welfare rights advice service
      provided by local government or voluntary organisations in North East England for
      independent living, socio-economically disadvantaged older people (aged >=60
      yrs), recruited from general (primary care) practices. METHODS/DESIGN: The study
      is a pragmatic, individually randomised, single blinded, wait-list controlled
      trial of welfare rights advice versus usual care, with embedded economic and
      qualitative process evaluations. The qualitative study will examine whether the
      intervention is delivered as intended; explore responses to the intervention and
      examine reasons for the trial findings; and explore the potential for translation
      of the intervention into routine policy and practice. The primary outcome is the
      effect on health-related quality of life, measured using the CASP 19
      questionnaire. Volunteer men and women aged >=60 years (1/household) will be
      identified from general practice patient registers. Patients in nursing homes or
      hospitals at the time of recruitment will be excluded. General practice
      populations will be recruited from disadvantaged areas of North East England,
      including urban, rural and semi-rural areas, with no previous access to targeted
      welfare rights advice services delivered to primary care patients. A minimum of
      750 participants will be randomised to intervention and control arms in a 1:1
      ratio. DISCUSSION: Achieving a trial design that is both ethical and acceptable
      to potential participants, required methodological compromises. The choice of
      follow-up length required a trade-off between sufficient time to demonstrate
      health impact and the need to allow the control group access to the intervention
      as early as possible. The study will have implications for fundamental
      understanding of social inequalities and how to tackle them, and provides a model
      for similar evaluations of health-orientated social interventions. If the health
      benefits of this intervention are proven, targeted welfare rights advice services
      should be extended to ensure widespread provision for older people and other
      vulnerable groups. CURRENT CONTROLLED TRIALS ISRCTN NUMBER: ISRCTN37380518.

PMID- 22639989
TI  - Mitral valve regurgitation: paradoxical behavior of dobutamine stress cardiac
      magnetic resonance imaging.
AB  - A 62-year-old woman with mitral regurgitation (MR) underwent cardiac magnetic
      resonance (CMR) and dobutamine stress CMR imaging, a widely used method to
      analyze left ventricular function and MR volumes. During dobutamine provocation
      at escalating doses, the left ventricular end-diastolic diameter (LVEDD)
      decreased, with a corresponding decrease in MR. At peak dobutamine dose, the
      LVEDD further decreased, with near complete relief of MR. Upon cessation of
      dobutamine provocation, the MR returned to predobutamine level. This case thereby
      demonstrates that MR may be reversible under certain conditions.

PMID- 22639990
TI  - Towards the understanding of Down syndrome using mouse models.
AB  - Down syndrome (DS) is the most common cause of mental retardation. Several DS
      mouse models with partial trisomy 16 homologous to human chromosome 21 have been
      developed, and our research group has been studying those mouse models. We have
      shown a dosage-dependent overexpression of genes in the trisomic region of the
      mouse. We have also described abnormalities including increased oxidative stress,
      increased lipid peroxidation, mitochondrial dysfunction, tau-hyperphosphorylation
      and overactivation of its phosphatases, impaired developmental and adult
      neurogenesis, histological abnormalities in brains including ventricle
      enlargements and minor neurodegenerations in those mice. These observations may
      contribute to the identification of responsible genes and understanding of
      molecular pathology of Down syndrome.

PMID- 22639991
TI  - Sonic hedgehog signaling coordinates the proliferation and differentiation of
      neural stem/progenitor cells by regulating cell cycle kinetics during development
      of the neocortex.
AB  - Sonic hedgehog (Shh) acts as a morphogen in normal development of various
      vertebrate tissues and organs. Shh signaling is essential for patterning and cell
      fate specification, particularly in the central nervous system. Shh signaling
      plays different roles depending on its concentration, area, and timing of
      exposure. During the development of the neocortex, a low level of Shh is
      expressed in the neural stem/progenitor cells as well as in mature neurons in the
      dorsal telencephalon. Shh signaling in neocortex development has been shown to
      regulate cell cycle kinetics of radial glial cells and intermediate progenitor
      cells, thereby maintaining the proliferation, survival and differentiation of
      neurons in the neocortex. During the development of the telencephalon, endogenous
      Shh signaling is involved in the transition of slow-cycling neural stem cells to
      fast-cycling neural progenitor cells. It seems that high-level Shh signaling in
      the ventral telencephalon is essential for ventral specification, while low-level
      Shh signaling in the dorsal telencephalon plays important roles in the fine
      tuning of cell cycle kinetics. The Shh levels and multiple functions of Shh
      signaling are important for proper corticogenesis in the developing brain. The
      present paper discusses the roles of Shh signaling in the proliferation and
      differentiation of neural stem/progenitor cells.

PMID- 22639992
TI  - Spastic quadriplegia in Down syndrome with congenital duodenal stenosis/atresia.
AB  - Down syndrome is an autosomal chromosome disorder, characterized by intellectual
      disability and muscle hypotonia. Muscle hypotonia is observed from neonates to
      adulthood in Down syndrome patients, but muscle hypertonicity is extremely
      unusual in this syndrome. During a study period of nine years, we found three
      patients with severe spastic quadriplegia among 20 cases with Down syndrome and
      congenital duodenal stenosis/atresia (3/20). However, we could find no patient
      with spastic quadriplegia among 644 cases with Down syndrome without congenital
      duodenal stenosis/atresia during the same period (0/644, P < 0.05). Further, we
      did not find any cases with spastic quadriplegia among 17 patients with
      congenital duodenal stenosis/atresia without Down syndrome admitted during the
      same period to use as a control group (0/17, P < 0.05). Our results suggest that
      congenital duodenal stenosis/atresia is a potential risk factor for spastic
      quadriplegia in patients with Down syndrome. Long-term survival is improving, and
      the large majority of people with Down syndrome are expected to live well into
      adult life. Management and further study for the various problems, representing a
      low prevalence but serious and specific to patients with Down syndrome, are
      required to improve their quality of life.

PMID- 22639993
TI  - Age-dependent change in behavioral feature in Rubinstein-Taybi syndrome.
AB  - Rubinstein-Taybi syndrome (RTS) is characterized by developmental delay,
      postnatal growth retardation, typical facial appearance, and broad thumbs and big
      toes. The behavioral phenotype of children with RTS has been described as
      friendly and having good social contacts; however, a short attention span and
      hyperactivity are sometimes present. Little attention has been paid to the
      behavioral aspects of adults with RTS. We conducted an observational study
      focusing on behavioral problems in adolescents and adults with RTS compared with
      children with RTS. A total of 63 patients with RTS and their caretakers answered
      self-administered questionnaires regarding behavioral features including the
      Child Behavior Checklist (CBCL). High total CBCL scores were observed, and the
      mean score was beyond the clinical cut-off point. After stratification into two
      groups according to age, the older group (>=14 years) displayed statistically
      significant higher scores for Anxious/Depression (P = 0.002) and Aggressive
      Behavior (P = 0.036) than the younger group (<=13 years). In analyses of single
      items, statistically significant differences between the younger group and the
      older group were found for 'Nervous, high-strung, or tense' (31.3% vs 67.7%, P =
      0.004) and 'Too fearful or anxious' (37.5% vs 64.5%, P = 0.032). Here, we showed
      that the specific behavioral phenotypes of RTS change during adolescence, with
      anxiety, mood instability, and aggressive behavior emerging as patients age. A
      clear need exists to follow-up patients with RTS to catch the eventual emergence
      of psychiatric problems with age. If necessary, pharmacological treatment should
      be considered.

PMID- 22639994
TI  - Characterization of heterotopic cell clusters in the hippocampus of the rat after
      prenatal treatment of methylazoxymethanol acetate.
AB  - Prenatal exposure of methylazoxymethanol acetate, a DNA methylating agent, to
      pregnant rats on embryonic day 15 is known to produce hippocampal malformation
      and laminar disorganization of the cerebral cortex. However, there are few
      studies to demonstrate developmental processes of abnormal structures in the
      hippocampus. In the present study, we examined complete serial sections of rat
      brains on postnatal day 0 to 2, which pretreated with methylazoxymethanol acetate
      on embryonic day 15. At birth, massive cellular clusters were found under the
      white matter of the cerebral cortex and then, a part of these clusters entered
      into the hippocampal CA1 sector on postnatal day 2. These ectopic cellular
      clusters in the CA1 were immunoreactive to anti-calbindin antibody, suggesting
      that the origin of these cellular clusters is equivalent to that of the cortical
      layer II/III neurons. Next, we injected FluoroGold into the lateral septal
      nucleus to examine hippocampo-septal projection. FluoroGold-labeled neurons were
      scattered in the ectopic cellular cluster, implying that CA1 pyramidal neurons
      project normally to the lateral septal nucleus. In conclusion, a majority of
      neurons found in the ectopic cellular cluster caused by prenatal
      methylazoxymethanol treatment is derived from cortical neurons, and some
      intrinsic pyramidal neurons in the CA1 of hippocampus are scattered throughout
      the ectopic cellular cluster.

PMID- 22639995
TI  - Expression of angiogenesis-related factors and inflammatory cytokines in placenta
      and umbilical vessels in pregnancies with preeclampsia and
      chorioamnionitis/funisitis.
AB  - We hypothesized that gene expression in placenta and umbilical vessels are
      affected by intrauterine environment and some of the expression in umbilical
      vessels originating from the fetus could reflect fetal condition of these
      complicated pregnancies. Expression of angiogenesis-related factors and
      inflammatory cytokines were examined in placenta and umbilical vessels to clarify
      the effects of intrauterine environment of pregnancies complicated by
      preeclampsia and chorioamnionitis/funisitis. Forty-six preterm cesarean section
      deliveries were classified into three groups based on maternal condition during
      prenatal monitoring: preeclampsia (PE) (n = 11), chorioamnionitis/funisitis (CAM)
      (n = 8), and preterm control (PC) (n = 27). Angiogenesis-related factors and
      inflammatory cytokines in placentas, umbilical arteries and umbilical veins were
      analyzed by RT-PCR and immunohistochemistry. We demonstrated that Ang-2, Tie-2,
      and Dll4 increase in the placentas of PE compared to PC for the first time, and
      we confirmed the findings of previous reports showing the high expression of HIF
      1alpha, sFlt-1, endoglin, leptin, and AT1R. Expression of angiogenesis-related
      factors, including HIF-1alpha, VEGF, angiopoietin, and TGF-beta systems, and
      inflammatory cytokines, such as TNF-alpha and IL-6, increased in umbilical
      vessels of PE. Umbilical veins of CAM showed a higher Dll4 level than did PC. In
      preeclampsia, abnormal expressions of angiogenesis-related factors related to
      lifestyle diseases in adulthood were seen in the placenta and umbilical vessels
      as compared to PC. Chorioamnionitis/funisitis showed only upregulation of DII4 in
      umbilical veins.

PMID- 22639996
TI  - Gastric hairballs in rabbits: significance in developmental toxicity study.
AB  - We surveyed 1053 pregnant rabbits of the Kbl:NZW strain collected from 27
      developmental toxicity studies to reveal the prevalence and significance of
      gastric hairballs. The incidence of hairballs was 2/525 (0.4%) in the control
      group and 17/528 (3.2%) in the high dose group. In the high dose group, 16 dams
      resulted in abortion or death. In addition, decreases in body weight and food
      consumption were more severe in dams with hairballs than in their group-mates
      without hairballs.

PMID- 22639997
TI  - Sirenomelia with a de novo balanced translocation 46,X,t(X;16)(p11.23;p12.3).
AB  - We report a female fetus with sirenomelia with 46,X,t(X;16)(p11.23;p12.3) de
      novo. Fluorescence in situ hybridization (FISH) with bacterial artificial
      chromosomes were employed for narrowing down the breakpoint regions. On
      chromosome 16, the breakpoint was mapped in the region of RP11-453F10 (19 920 640
      20 118 153 bp from 16pter). On chromosome X, the breakpoint was mapped in the
      region of RP11-794A15 (47 333 744-47 524 066 bp from Xpter). This is the first
      case report of sirenomelia associated with translocations. The abnormal
      phenotype, associated with a balanced translocation, was caused by deletion or
      breakage of dosage-sensitive genes of the breakpoint, disruption of an imprinted
      gene, or uniparental disomy. Although the parental origin of normal 16 and
      der(16) remained undetermined, this case will provide insight into the
      pathogenetic mechanism of sirenomelia.

PMID- 22639998
TI  - Prenatal diagnosis of a huge facial tumor: report of a rare case and literature
      review.
AB  - Neonatal tumors are reported to occur in approximately 17-121 per million live
      births worldwide. They are often diagnosed by ultrasonography after mid
      pregnancy. Teratomas are the most frequent solid neoplasms, accounting for
      between one-quarter and one-third of cases. Here, we describe the prenatal
      diagnosis of a fetal face teratoma located on the right temporal side at 26 weeks
      of gestation. Besides 2D and 4D ultrasound imaging, fetal magnetic resonance
      imaging provides substantial support in perinatal management and promotes the
      perception of fetal malformations by the family. Extreme intrauterine growth of
      the tumor with remarkable pressure to the surrounding facial structures and good
      perinatal prognosis following complete tumoral resection are reviewed.

PMID- 22639999
TI  - Adult with sacral lipomyelomeningocele covered by an anomalous bone articulated
      with iliac bone: computed tomography and magnetic resonance images.
AB  - The present paper reports and discusses a case of sacral lipomyelomeningocele
      with an anomalous long bone articulating with the left iliac bone in a 40-year
      old female. That patient had a monozygotic twin sister who had normal spine. The
      findings were incidental during an evaluation for a urinary tract infection. The
      computed tomography (CT) and magnetic resonance (MR) images revealed sacral
      dysraphism, lipomyelomeningocele, tethered spinal cord, and profound subcutaneous
      fat in the sacrococcygeal region. In addition, an anomalous bony strut was
      demonstrated on the posterior aspect of the sacrum, covering the sacral defect
      and the associated lipomyelomeningocele. The 3-D CT images of the anomalous bone
      associated with the sacral lipomyelomeningocele and the putative embryologic
      process are presented with a review of the literature.

PMID- 22640000
TI  - Do combined alternating sessions of 1540 nm nonablative fractional laser and
      percutaneous collagen induction with trichloroacetic acid 20% show better results
      than each individual modality in the treatment of atrophic acne scars? A
      randomized controlled trial.
AB  - BACKGROUND: There have been no well-controlled studies evaluating the efficacy of
      combining 1540 nm nonablative fractional laser with percutaneous collagen
      induction (PCI) and trichloroacetic acid (TCA) 20% in the treatment of atrophic
      acne scars. OBJECTIVE: We hypothesized that combined alternating sessions of both
      modalities would show better results than each individual modality. METHODS AND
      MATERIALS: Thirty-nine patients with post acne atrophic scars were included in
      this study. Patients were randomly equally divided into three groups; group 1 was
      subjected to six sessions of PCI combined with TCA 20% in the same session, group
      2 was subjected to six sessions of 1540 nm fractional laser and group 3 was
      subjected to combined alternating sessions of the previously mentioned two
      modalities. RESULTS: Scar severity scores improved by a mean of 59.79% (95% CI
      47.38-72.21) (p < 0.001) in group 1, a mean of 61.83% (95% CI 54.09-69.56) (p <
      0.001) in group 2 and a mean of 78.27% (95% CI 74.39-82.15) (p < 0.001) in group
      3. The difference in the degree of improvement was statistically significant when
      comparing the three groups using ANOVA test (p = 0.004). CONCLUSION: The current
      work recommends combining 1540 nm nonablative fractional laser in alternation
      with PCI and TCA 20% in the treatment of atrophic acne scars.

PMID- 22640001
TI  - Melatonin promotes seminal root elongation and root growth in transgenic rice
      after germination.
AB  - The effect of melatonin on root growth after germination was examined in
      transgenic rice seedlings expressing sheep serotonin N-acetyltransferase (NAT).
      Enhanced melatonin levels were found in T(3) homozygous seedlings because of the
      ectopic overexpression of sheep NAT, which is believed to be the rate-limiting
      enzyme in melatonin biosynthesis in animals. Compared with wild-type rice seeds,
      the transgenic rice seeds showed enhanced seminal root growth and an analogous
      number of adventitious roots 4 and 10 days after seeding on half-strength
      Murashige and Skoog medium. The enhanced initial seminal root growth in the
      transgenic seedlings matched their increased root biomass well. We also found
      that treatment with 0.5 and 1 MUM melatonin promoted seminal root growth of the
      wild type under continuous light. These results indicate that melatonin plays an
      important role in regulating both seminal root length and root growth after
      germination in monocotyledonous rice plants. This is the first report on the
      effects of melatonin on root growth in gain-of-function mutant plants that
      produce high levels of melatonin.

PMID- 22640003
TI  - Mapping breastfeeding services: a method to inform effective implementation and
      evaluation of evidence-based policy in practice.
AB  - This paper aims to introduce a method for mapping local service provision to
      local demographic and health outcome data, to inform evidence-based policy and
      practice in public health. A mapping exercise was conducted in London, England
      with the aims of: (1) describing services provided for breastfeeding women in
      primary and tertiary health care sectors and government, voluntary and private
      sectors; and (2) linking this information with routine data on deprivation,
      breastfeeding rates and health outcomes. Quantitative data on local breastfeeding
      services were collected via an online questionnaire by a designated 'mapping
      lead' in each locality. Data were collected at the level of individual health
      care organisations on the provision, nature and management of breastfeeding
      services, and related organisational inputs such as leadership, staffing,
      accreditation and policy. Demographic and health outcome data were identified
      from existing routine national data collections. Ninety-one per cent of eligible
      acute and primary care organisations participated in the mapping exercise. A
      range of mapping tools and profile were developed and launched in 2009
      (http://atlas.chimat.org.uk/IAS/dataviews/view?viewId=66). These tools can be
      used for descriptive analyses of service provision on the basis of local need.
      Comparative analyses on the impact of service provision on breastfeeding or
      health outcomes will be feasible from 18 months of data collection onwards. This
      case study has demonstrated the potential utility of this mapping method to
      inform effective implementation and evaluation of public health policy in
      practice consistent with the World Health Organisation framework. Formal
      evaluation of the utility of the tools is recommended.

PMID- 22640002
TI  - Towards a definition of refractory neuropathic pain for epidemiological research.
      An international Delphi survey of experts.
AB  - BACKGROUND: Best current estimates of neuropathic pain (NeuP) prevalence come
      from studies using various screening detecting pain with probable neuropathic
      features; the proportion experiencing significant, long-term NeuP, and the
      proportion not responding to standard treatment are unknown. These "refractory"
      cases are the most clinically important to detect, being the most severe,
      requiring specialist treatment. METHODS: We report an international Delphi survey
      of experts in NeuP, aiming for consensus on the features required to define, for
      epidemiological research: (1) neuropathic pain; and (2) when NeuP is
      "refractory". A web-based questionnaire was developed and data collected from
      three rounds of questionnaires from nineteen experts. RESULTS: There was good
      consensus on essential inclusion of six items to identify NeuP ("prickling,
      tingling, pins & needles", "pain evoked by light touch", "electric shocks or
      shooting pain", "hot or burning" pain, "brush allodynia on self-examination", and
      "relevant history") and on some items that were non-essential. Consensus was also
      reached on components of a "refractory NeuP" definition: minimum duration (one
      year); number of trials of drugs of known effectiveness (four); adequate duration
      of these trials (three months / maximum tolerated); outcomes of treatment (pain
      severity, quality of life). Further work needs to validate these proposed
      criteria in general population research. CONCLUSIONS: This paper presents an
      international consensus on measuring the epidemiology of refractory neuropathic
      pain. This will be valuable in reaching an agreed estimate of the prevalence of
      neuropathic pain, and the first estimate of refractory neuropathic pain
      prevalence.

PMID- 22640004
TI  - Plasma cell panniculitis of the cheek.

PMID- 22640005
TI  - Host responses in Norway spruce roots induced to the pathogen Ceratocystis
      polonica are evaded or suppressed by the ectomycorrhizal fungus Laccaria bicolor.
AB  - The outcome of a compatible mycorrhizal interaction is different from that in a
      compatible plant-pathogen interaction; however, it is not clear what mechanisms
      are used to evade or suppress the host defence. The aim of this work is to reveal
      differences between the interaction of Norway spruce roots to the pathogen
      Ceratocystis polonica and the ectomycorrhizal Laccaria bicolor, examine if L.
      bicolor is able to evade inducing host defence responses typically induced by
      pathogens, and test if prior inoculation with the ectomycorrhizal fungus affects
      the outcome of a later challenge with the pathogen. The pathogen was able to
      invade the roots and caused extensive necrosis, leading to seedling death, with
      or without prior inoculation with L. bicolor. The ectomycorrhizal L. bicolor
      colonised primary roots of the Norway spruce seedlings by partly covering,
      displacing and convoluting the cells of the outer root cortex, leaving the
      seedlings healthy. We detected increased total peroxidase activity, and staining
      indicating increased lignification in roots as a response to C. polonica. In L.
      bicolor inoculated roots there was no increase in total peroxidase activity, but
      an additional highly acidic peroxidase isoform appeared that was not present in
      healthy roots, or in roots invaded by the pathogen. Increased protease activity
      was detected in roots colonised by C. polonica, but little protease activity was
      detected in L. bicolor inoculated roots. These results suggest that the pathogen
      efficiently invades the roots despite the induced host defence responses, while
      L. bicolor suppresses or evades inducing such host responses in this experimental
      system.

PMID- 22640006
TI  - Estimation of (co)variances for genomic regions of flexible sizes: application to
      complex infectious udder diseases in dairy cattle.
AB  - BACKGROUND: Multi-trait genomic models in a Bayesian context can be used to
      estimate genomic (co)variances, either for a complete genome or for genomic
      regions (e.g. per chromosome) for the purpose of multi-trait genomic selection or
      to gain further insight into the genomic architecture of related traits such as
      mammary disease traits in dairy cattle. METHODS: Data on progeny means of six
      traits related to mastitis resistance in dairy cattle (general mastitis
      resistance and five pathogen-specific mastitis resistance traits) were analyzed
      using a bivariate Bayesian SNP-based genomic model with a common prior
      distribution for the marker allele substitution effects and estimation of the
      hyperparameters in this prior distribution from the progeny means data. From the
      Markov chain Monte Carlo samples of the allele substitution effects, genomic
      (co)variances were calculated on a whole-genome level, per chromosome, and in
      regions of 100 SNP on a chromosome. RESULTS: Genomic proportions of the total
      variance differed between traits. Genomic correlations were lower than pedigree
      based genetic correlations and they were highest between general mastitis and
      pathogen-specific traits because of the part-whole relationship between these
      traits. The chromosome-wise genomic proportions of the total variance differed
      between traits, with some chromosomes explaining higher or lower values than
      expected in relation to chromosome size. Few chromosomes showed pleiotropic
      effects and only chromosome 19 had a clear effect on all traits, indicating the
      presence of QTL with a general effect on mastitis resistance. The region-wise
      patterns of genomic variances differed between traits. Peaks indicating QTL were
      identified but were not very distinctive because a common prior for the marker
      effects was used. There was a clear difference in the region-wise patterns of
      genomic correlation among combinations of traits, with distinctive peaks
      indicating the presence of pleiotropic QTL. CONCLUSIONS: The results show that it
      is possible to estimate, genome-wide and region-wise genomic (co)variances of
      mastitis resistance traits in dairy cattle using multivariate genomic models.

PMID- 22640007
TI  - Highly selective mild stepwise allylation of N-methoxybenzamides with allenes.
AB  - An efficient Rh(III)-catalyzed stepwise ortho allylation of N-methoxybenzamides 1
      with polysubstituted allenes is reported. This C-H functionalization involving
      allenes is conducted under very mild conditions (-20  degrees C or room
      temperature) and compatible with ambient air and moisture, and it can be applied
      to terminal or internal allenes with different synthetically attractive
      functional groups. Highly efficient axial chirality transfer has been realized,
      yielding optically active lactones.

PMID- 22640008
TI  - Allogeneic haematopoietic stem cell transplantation for chronic lymphocytic
      leukaemia: outcome in a 20-year cohort.
AB  - The curative potential of allogeneic haematopoietic stem cell transplant (allo
      HSCT) in chronic lymphocytic leukaemia CLL is established, with a demonstrated
      role for graft-versus-leukaemia and less certainty for other factors in
      determining outcome. The first two decades of CLL patients proceeding to allo
      HSCT at the Leukaemia/Bone Marrow Transplant Program of British Columbia (n = 49
      consecutive, 1991-2009) were studied to clarify factors predicting outcome. The
      donor was related in 29 (59%) and unrelated in 20 (41%). Conditioning was reduced
      intensity in 27 (55%) and myeloablative in 22 (45%). Thirty-one of 49 patients
      survive with median follow-up of 5 years (0.2-15). Cumulative incidence of non
      relapse mortality; complete remission (CR); clearance of fluorescence in situ
      hybridization (FISH) abnormality and progression at 10 years was 36%; 69%; 55%
      and 22%. Overall survival (OS) was 63% at 2 years; 55% at 5 years and beyond.
      Factors predicting OS (P value by log rank <0.05) were: comorbidity index <3,
      FISH rank (Dohner) and 17p deletion, alemtuzumab pre-HSCT, achievement of CR post
      HSCT, donor chimerism >90%, clearance of FISH abnormality post-HSCT and absence
      of high-grade (3-4) graft-versus-host disease. Results from this province-wide,
      two-decade cohort demonstrated that a substantial proportion of patients with
      high-risk CLL become long term disease-free survivors.

PMID- 22640009
TI  - Is it time to abandon paper? The use of emails and the Internet for health
      services research--a cost-effectiveness and qualitative study.
AB  - RATIONALE: A multidisciplinary primary care clinic in Sydney, Australia, was
      planning to use electronic questionnaires to measure patient-reported outcomes.
      METHODS: Semi-structured interviews with 20 patients were undertaken to explore,
      among other things, practical issues regarding different questionnaire formats.
      The response rates and costs of email versus postal invitations were also
      evaluated. RESULTS: Compared with postal invitations, email invitations offered a
      cost-effective and practical alternative, with a greater proportion of patients
      volunteering for an interview. Assuming the interface is well-designed and user
      friendly, many patients were happy to use the Internet to answer questionnaires.
      Most patients thought alternate formats should also be offered. Patients
      discussed advantages and disadvantages of the Internet format. Although more
      younger patients and females had given the clinic an email address; both sexes,
      and young and old patients, expressed strong preferences for either wanting or
      not wanting to use the Internet. CONCLUSION: Researchers should consider using
      email invitations as a cost-effective first-line strategy to recruit patients to
      participate in health services research. Internet questionnaires are potentially
      cheaper than paper questionnaires, and the format is acceptable to many patients.
      However, for the time being, concurrent alternate formats need to be offered to
      ensure wider acceptability and to maximize response rates.

PMID- 22640010
TI  - Meta-analysis on risky sexual behaviour of men: consistent findings from
      different parts of the world.
AB  - The aim of this analysis was to determine the consistency of higher-risk sex
      practice among educated and/or wealthy men in different parts of the world. Meta
      analysis was done on risky sexual behaviour of men using the recent Demographic
      and Health Surveys (DHS 2003-2009) data from 26 countries in and outside Africa.
      DHS data were accessed through electronic databases. In this analysis, since
      there was significant heterogeneity (I(2)>50%) among surveys findings, random
      effects analytic model was applied. Mantel-Haenszel statistical method was used
      to calculate the pooled odds ratios across countries. Out of 79,736 men aged 15
      49 years who had sexual intercourse in 12 months preceding the respective survey,
      35.7% reported to have higher-risk sex. The proportion of higher-risk sex was
      found positively correlated with increased wealth index. In 24 countries, higher
      risk sex was found to have highly statistically significant association with men
      living in urban areas, educated to secondary and above, and owned middle to
      highest wealth index. The overall condom use during the last higher-risk sexual
      encounter was 47% but condom use was better practiced by educated men. Nearly in
      two-thirds of countries reported HIV-prevalence, the proportion of HIV infection
      was highest among better educated. In conclusion, this meta-analysis has shown
      that risk taking sexual behaviour is invariably associated with high educational
      attainment, urban residence and better wealth index regardless of geographic
      location of men participated in the surveys.

PMID- 22640011
TI  - Deletion of hypothetical wall teichoic acid ligases in Staphylococcus aureus
      activates the cell wall stress response.
AB  - The Staphylococcus aureus cell wall stress stimulon (CWSS) is activated by cell
      envelope-targeting antibiotics or depletion of essential cell wall biosynthesis
      enzymes. The functionally uncharacterized S. aureus LytR-CpsA-Psr (LCP) proteins,
      MsrR, SA0908 and SA2103, all belong to the CWSS. Although not essential, deletion
      of all three LCP proteins severely impairs cell division. We show here that VraSR
      dependent CWSS expression was up to 250-fold higher in single, double and triple
      LCP mutants than in wild type S. aureus in the absence of external stress. The
      LCP triple mutant was virtually depleted of wall teichoic acids (WTA), which
      could be restored to different degrees by any of the single LCP proteins.
      Subinhibitory concentrations of tunicamycin, which inhibits the first WTA
      synthesis enzyme TarO (TagO), could partially complement the severe growth defect
      of the LCP triple mutant. Both of the latter findings support a role for S.
      aureus LCP proteins in late WTA synthesis, as in Bacillus subtilis where LCP
      proteins were recently proposed to transfer WTA from lipid carriers to the cell
      wall peptidoglycan. Intrinsic activation of the CWSS upon LCP deletion and the
      fact that LCP proteins were essential for WTA-loading of the cell wall, highlight
      their important role(s) in S. aureus cell envelope biogenesis.

PMID- 22640012
TI  - A qualitative study of leadership characteristics among women who catalyze
      positive community change.
AB  - BACKGROUND: Leadership is critical to making changes at multiple levels of the
      social ecological model, including the environmental and policy levels, and will
      therefore likely contribute to solutions to the obesity epidemic and other public
      health issues. The literature describing the relative leadership styles and
      strengths of women versus men is mixed and virtually all research comes from
      sectors outside of public health. The purpose of this qualitative study is to
      identify specific leadership skills and characteristics in women who have
      successfully created change predominantly within the food and physical activity
      environments in their communities and beyond. The second purpose of this study is
      to understand best practices for training and nurturing women leaders, to
      maximize their effectiveness in creating social change. METHODS: Key informant
      interviews were conducted with 16 women leaders in the public health sector from
      November 2008 through February 2010. The sample represented a broad spectrum of
      leaders from across the United States, identified through web searches and
      through networks of academic and professional colleagues. Most were working on
      improving the food and physical activity environments within their communities.
      Questions were designed to determine leaders' career path, motivation,
      characteristics, definition of success, and challenges. The initial coding
      framework was based on the questioning structure. Using a grounded theory
      approach, additional themes were added to the framework as they emerged. The
      NVivo program was used to help code the data. RESULTS: Respondents possessed a
      vision, a strong drive to carry it out, and an ability to mobilize others around
      the vision. Their definitions of success most often included changing the lives
      of others in a sustainable way. Persistence and communications skills were
      important to their success. The mentoring they received was critical. Challenges
      included fundraising and drifting from their original mission. CONCLUSIONS: These
      findings may be used to help develop or inform a model of women's leadership in
      public health and to improve the training and nurturance of leaders who promote
      health in their communities and beyond.

PMID- 22640013
TI  - Analysis of cases with cesarean scar pregnancy.
AB  - AIM: To discuss the early diagnosis and effective treatment strategy of cesarean
      scar pregnancy (CSP). MATERIAL AND METHODS:  We reviewed 17 patients in our
      department diagnosed with CSP between 2005 and 2010, including clinical
      characteristics, early diagnosis, treatment methods, side-effects and prognosis.
      RESULTS: The average duration of gestation at diagnosis was 46 days (range 37-82)
      and the interval between CSP and last cesarean scar was 6 years (range 2-15).
      Fourteen (82%) patients presented with slight vaginal bleeding and two (12%)
      complained of abdominal discomfort. Fourteen patients were diagnosed with CSP by
      transvaginal color Doppler ultrasonography (TVCDUS). Magnetic resonance imaging
      (MRI) was performed in two cases of CSP when the diagnosis by TVCDUS was
      difficult. One patient was diagnosed by histological examination of hysterectomy
      specimens due to life-threatening bleeding during curettage. Seven patients
      initially diagnosed with CSP before pregnancy termination were treated
      conservatively to preserve the uterus without causing maternal complications, ten
      patients underwent curettage due to incorrect diagnosis, eight patients had
      excessive vaginal bleeding during curettage and three patients underwent
      emergency hysterectomy due to hypovolemic shock. CONCLUSION: CSP does not have
      any specific symptoms and can be easily diagnosed incorrectly. Confirmation of a
      portion of gestational sac in the uterus is important and TVCDUS is the first
      line tool for early diagnosis of CSP. Physicians never perform curettage at
      diagnosis with CSP, but curettage after uterine artery embolism or methotrexate
      are better treatments of choice to terminate CSP.

PMID- 22640014
TI  - Hepatic portal venous gas and "the aquarium sign" due to intussusception in
      kawasaki disease.
AB  - The presence of hepatic portal venous gas (HPVG) may be secondary to bowel
      necrosis, mechanical distension, or intraabdominal sepsis. We describe an unusual
      and hitherto unreported presence of HPVG manifesting as gas embolization and the
      unique "aquarium sign" in a patient of Kawasaki's disease. Continuous passage of
      bubble-like echoes flowing from the hepatic portal venous system into the
      inferior vena cava and right-sided chambers of heart was noted on
      echocardiography. The patient was treated with intravenous immune-globulins and
      made an uneventful recovery.

PMID- 22640016
TI  - Cell-cell communication in the resistance vasculature: the past, present, and
      future.
AB  - Cell-cell communication among neighboring vascular cells plays an important role
      in blood flow control. In this overview, we highlight a series of expert opinion
      articles focused on key issues related to the foundational nature and functional
      importance of electrical and second messenger communication. These manuscripts
      are written in an opinionated manner to provoke thought and to illuminate new
      emerging areas of investigation.

PMID- 22640015
TI  - Subcellular localization of regulator of G protein signaling RGS7 complex in
      neurons and transfected cells.
AB  - The R7 family of regulators of G protein signaling (RGS) is involved in many
      functions of the nervous system. This family includes RGS6, RGS7, RGS9, and RGS11
      gene products and is defined by the presence of the characteristic first found in
      Disheveled, Egl-10, Pleckstrin (DEP), DEP helical extension (DHEX), Ggamma-like,
      and RGS domains. Herein, we examined the subcellular localization of RGS7, the
      most broadly expressed R7 member. Our immunofluorescence studies of retinal and
      dorsal root ganglion neurons showed that RGS7 concentrated at the plasma membrane
      of cell bodies, in structures resembling lamellipodia or filopodia along the
      processes, and at the dendritic tips. At the plasma membrane of dorsal root
      ganglia neurons, RGS7 co-localized with its known binding partners R7 RGS binding
      protein (R7BP), Galphao, and Galphaq. More than 50% of total RGS7-specific
      immunofluorescence was present in the cytoplasm, primarily within numerous small
      puncta that did not co-localize with R7BP. No specific RGS7 or R7BP
      immunoreactivity was detected in the nuclei. In transfected cell lines, ectopic
      RGS7 had both diffuse cytosolic and punctate localization patterns. RGS7 also
      localized in centrosomes. Structure-function analysis showed that the punctate
      localization was mediated by the DEP/DHEX domains, and centrosomal localization
      was dependent on the DHEX domain.

PMID- 22640017
TI  - Fetal volume measurements with three dimensional ultrasound in the first
      trimester of pregnancy, related to pregnancy outcome, a prospective cohort study.
AB  - BACKGROUND: First trimester growth restriction is associated with an increased
      risk of adverse birth outcomes (preterm birth, low birth weight and small for
      gestational age at birth). The differences between normal and abnormal growth in
      early pregnancy are small if the fetal size is measured by the crown-rump-length.
      Three-dimensional ultrasound volume measurements might give more information
      about fetal development than two-dimensional ultrasound measurements. Detection
      of the fetus with a small fetal volume might result in earlier detection of high
      risk pregnancies and a better selection of high risk pregnancies. METHODS: A
      prospective cohort study, performed at the Maxima Medical Centre, in Eindhoven
      Veldhoven, the Netherlands. During the routine first trimester scan with nuchal
      translucency measurement 500 fetal volumes will be obtained. The gestational age
      is based on the first day of the last menstrual period in a regular menstrual
      cycle and by the crown-rump-length. The acquired datasets are collected and
      stored on a hard disk for offline processing and volume calculation. The
      investigator who performs the volume measurements is blinded for the results of
      the first trimester scan. The manual mode will be used to outline the Region Of
      Interest, the fetal head and rump, in all cross sections. The fetal volumes are
      calculated with a rotational step of 9 degrees .First, the relation between fetal
      volume and gestational age, for a set of participants with normal pregnancies
      (training set), will be assessed. This model will then be used to determine
      expected values of fetal volume for a normal pregnancy, which will be referred to
      as expected normal values. Secondly, for a new set of participants with normal
      pregnancies and a set of participants with complicated pregnancies (together
      defined as validation set), the observed fetal volumes (FV(observed)) are
      compared with their expected normal values (FV(expected)) and expressed as a
      percentage of the expected normal value. The mean difference in percentage error
      between the set of normal versus complicated pregnancies will then be compared
      using the independent-samples t-test. Finally, logistic regression analysis will
      be applied to the validation set of participants to analyze the possibility of
      predicting the pregnancy outcome after fetal volume calculation in the first
      trimester, using this percentage error. DISCUSSION: After this study it is clear
      whether FV measurement in the first trimester can detect high risk pregnancies.
      If it is possible to detect these pregnancies, more intensive follow up in these
      pregnancies might result in fewer complicated pregnancies and fewer fetal
      morbidities.

PMID- 22640018
TI  - NG2 and NG2-positive cells delineate focal cerebral infarct demarcation in rats.
AB  - Focal cerebral ischemia induces cellular responses that may result in secondary
      tissue damage. We recently demonstrated multi-facetted spatial and temporal
      patterns of neuroinflammation by multimodal imaging. In the present study, we
      especially focus on the separation of vital and necrotic tissue, which enabled us
      to define a demarcation zone. Focal cerebral ischemia was induced via macrosphere
      embolization of the middle cerebral artery in Wistar rats. Subsequent cellular
      processes were investigated immunohistochemically from 3 to 56 days after onset
      of ischemia. We detected several infarct subareas: a necrotic infarct core and
      its margin adjacent to a nerve/glial antigen 2 (NG2)+ zone delineating it from a
      vital peri-infarct zone. Initially transition from necrotic to vital tissue was
      gradual; later on necrosis was precisely separated from vital tissue by a narrow
      NG2+ belt that was devoid of astrocytes, oligodendrocytes or neurons. Within this
      demarcation zone NG2+ cells associate with ionized calcium binding adaptor
      molecule 1 (Iba1) but not with GFAP, neuronal nuclear antigen (NeuN) or 2', 3'
      cyclic nucleotide 3'-phosphodiesterase (CNPase). During further infarct
      maturation NG2 seemed to be positioned in the extracellular matrix (ECM) of the
      demarcation zone, whereas Iba1+ cells invaded the necrotic infarct core and GFAP+
      cells built a gliotic containing belt between the lesion and NeuN+ unaffected
      tissue. Overall, our data suggested that NG2 proteoglycan expression and
      secretion hallmarked demarcation as a process that actively separated necrosis
      from vital tissue and therefore decisively impacts secondary neurodegeneration
      after ischemic stroke.

PMID- 22640019
TI  - Multiple trichofolliculomas on unusual sites: a case report and review of the
      literature.

PMID- 22640021
TI  - Social media and health professionals: making the "net" work for you.

PMID- 22640022
TI  - Grief reaction model of families who experienced acute bereavement in Japan.
AB  - The present study clarified the structure of factors that affect grief reactions
      of families who experienced acute bereavement in critical care settings in Japan.
      Sixty-four families who experienced acute bereavement answered a questionnaire.
      The questionnaire included the Miyabayashi Grief Measurement, recognition of
      bereavement, Multidimensional Scale of Perceived Social Support, and the Tri
      Axial Coping Scale. We analyzed the causal structure regarding the relationship
      of stress recognition, coping, and grief reactions using structural equation
      modeling. The greatest influence on grief reactions of bereaved families was
      stress recognition. Factors that influenced stress recognition were subjective
      degree of sadness, acceptance of bereavement, regret for bereavement, and
      recognition of a peaceful death. These results show that the quality of end-of
      life care in critical care settings is an important factor that affects bereaved
      families' stress recognition and grief reactions. Nurses and medical staff must
      provide end-of-life care to help family members accept the death of their loved
      one and reduce regrets as much as possible.

PMID- 22640020
TI  - An ancient history of gene duplications, fusions and losses in the evolution of
      APOBEC3 mutators in mammals.
AB  - BACKGROUND: The APOBEC3 (A3) genes play a key role in innate antiviral defense in
      mammals by introducing directed mutations in the DNA. The human genome encodes
      for seven A3 genes, with multiple splice alternatives. Different A3 proteins
      display different substrate specificity, but the very basic question on how
      discerning self from non-self still remains unresolved. Further, the expression
      of A3 activity/ies shapes the way both viral and host genomes evolve. RESULTS: We
      present here a detailed temporal analysis of the origin and expansion of the A3
      repertoire in mammals. Our data support an evolutionary scenario where the genome
      of the mammalian ancestor encoded for at least one ancestral A3 gene, and where
      the genome of the ancestor of placental mammals (and possibly of the ancestor of
      all mammals) already encoded for an A3Z1-A3Z2-A3Z3 arrangement. Duplication
      events of the A3 genes have occurred independently in different lineages: humans,
      cats and horses. In all of them, gene duplication has resulted in changes in
      enzyme activity and/or substrate specificity, in a paradigmatic example of
      convergent adaptive evolution at the genomic level. Finally, our results show
      that evolutionary rates for the three A3Z1, A3Z2 and A3Z3 motifs have
      significantly decreased in the last 100 Mya. The analysis constitutes a textbook
      example of the evolution of a gene locus by duplication and
      sub/neofunctionalization in the context of virus-host arms race. CONCLUSIONS: Our
      results provide a time framework for identifying ancestral and derived genomic
      arrangements in the APOBEC loci, and to date the expansion of this gene family
      for different lineages through time, as a response to changes in
      viral/retroviral/retrotransposon pressure.

PMID- 22640023
TI  - Intravenous fluid administration and monitoring for adult ward patients in a
      teaching hospital.
AB  - Many acutely unwell, hospitalized patients receive continuous intravenous (IV)
      fluids. Complications of IV fluid administration include electrolyte
      abnormalities and fluid overload, which be detected by appropriate IV fluid
      administration and monitoring practices. This prospective clinical audit
      described the administration and monitoring of maintenance IV fluid in ward
      patients in an Australian tertiary teaching hospital. Of 332 inpatients (98%), 85
      (26%) were receiving IV fluids. Serum electrolyte and renal function measurements
      were obtained in 85% versus 65% of patients receiving IV fluids versus no IV
      fluids (P < 0.001). Fluid balance charts were being maintained for 94% versus 44%
      of patients receiving IV fluids versus no IV fluids (P < 0.001). Body weight
      measurements were documented for 15% versus 14% for patients receiving IV fluids
      versus no IV fluids (P = 0.078). Findings show that approximately one-quarter of
      adult ward patients in our hospital received IV fluids. Monitoring of such
      patients using regular blood tests and fluid balance charts is high, but patient
      weight measurements are low. Why hospitalized patients who require maintenance IV
      fluids do not have regular body weight measurements requires further
      investigation.

PMID- 22640024
TI  - Age-friendly nursing interventions in the management of older people in emergency
      departments.
AB  - Older people are high users of emergency department services, and on
      presentation, are often acutely ill. Nurses working in the emergency department
      are at the forefront of dealing with these challenges, by providing care that is
      specifically tailored to meet the needs of the older population and reducing the
      risks of adverse health outcomes during their stay in the emergency department.
      The ideal age-friendly emergency department environment supports the strengths
      and abilities of the older person, protects them against harm, and empowers
      individuals and their carers to be actively involved in decision-making. This
      information sheet focuses on the best-available evidence on age-friendly nursing
      interventions in the management of older patients during their stay in emergency
      department.

PMID- 22640025
TI  - Seasonal variations in injury rates in children: evidence from a 10-year study in
      the Veneto Region, Italy.
AB  - The objective of this study was to investigate the long term trend of pediatric
      injuries in Veneto Region (North-East of Italy) over 10 years, evaluating if
      seasonality in injury hospitalisations exists. Regional data on hospital
      admissions during the period 2000-2009 were analysed. Injury was defined as any
      condition identified by the International Classification of Diseases, 9th
      edition, Clinical Modification (ICD-9-CM) codes 800-999, excluding late effects
      from injury (ICD-9-CM codes 905-909), and complications of surgical and medical
      care, not classified elsewhere (ICD-9-CM code 995-999) in the first diagnostic
      field. Cyclic trends in seasonality of injuries were tested with Nam test. Thirty
      five thousand seven hundred and fifty-one hospitalisations due to an injury have
      been recorded. Significant seasonal variation in hospitalisations for injuries
      was observed, with a summer to winter ratio ranging from 1.8 for minor injuries
      to 2.0 for severe injuries (p <0.001). The observed pattern of increased
      admission in the summer months should guide resource planning and implementation
      of preventive strategies. 

PMID- 22640026
TI  - Role of different negative pressure values in the process of infected wounds
      treated by vacuum-assisted closure: an experimental study.
AB  - Vacuum-assisted closure (VAC) device is widely used to treat infected wounds in
      clinical work. Although the effect of VAC with different negative pressure values
      is well established, whether different negative pressures could result in varying
      modulation of wound relative cytokines was not clear. We hypothesise that instead
      of the highest negative pressure value the suitable value for VAC is the one
      which is the most effective on regulating wound relative cytokines. Infected
      wounds created on pigs' back were used to investigate the effects of varying
      negative pressure values of VAC devices. Wounds were treated with VAC of
      different negative pressure values or moist gauze, which was set as control. The
      VAC foam, semiocclusive dresses and moist gauze were changed on days 3, 5, 7 and
      9 after wounds were created. When changing dressings, tissues from wounds were
      harvested for bacteria count and histology examination including Masson's
      trichrome stain and immunohistochemistry for microvessels. Western blot was
      carried out to test the expression of vascular endothelial growth factor (VEGF)
      and basic fibroblast growth factor (bFGF). Results showed that on days 3 and 5
      the number of bacteria in wounds treated by VAC with 75, 150, 225 and 300 mmHg
      was significantly decreased compared with that in wounds treated by gauze and 0
      mmHg pressure value. However, there was no difference in wounds treated with
      negative pressure values of 75 , 150, 225 and 300 mmHg at any time spot.
      Immunohistochemistry showed that more microvessels were generated in wounds
      treated by VAC using 75 and 150 mmHg negative pressure comparing with that using
      225 and 300 mmHg on days 3 and 5. However this difference vanished on days 7 and
      9. Morphological evaluation by Masson's trichrome staining showed increased
      collagen deposition in VAC of 75 and 150 mmHg compared with that in VAC of 225
      and 300 mmHg. Western blot showed that the expression of VEGF and bFGF
      significantly increased when the wounds treated with 75 and 150 mmHg negative
      pressure values compared with the wounds treated with 225 and 300 mmHg on day 5.
      Treatment using VAC with different negative pressure values more than 75 mmHg has
      similar efficiency on reducing bacteria in the infected wound. VAC with negative
      pressure values of 75 and 150 mmHg promote wound healing more quickly than other
      pressure values. Moreover, comparing with vigorous negative pressure, relatively
      moderate pressures contribute to wound healing via accelerated granulation
      growth, increased angiogenic factor production and improved collagen fibre
      deposition. Further study of this model may show other molecular mechanisms. 

PMID- 22640027
TI  - Theoretical study of exchange coupling in 3d-Gd complexes: large magnetocaloric
      effect systems.
AB  - Polynuclear 3d transition metal-Gd complexes are good candidates to present large
      magnetocaloric effect. This effect is favored by the presence of weak
      ferromagnetic exchange interactions that have been investigated using methods
      based on Density Functional Theory. The first part of the study is devoted to
      dinuclear complexes, focusing on the nature and mechanism of such exchange
      interactions. The presence of two bridging ligands is found more favorable for
      ferromagnetic coupling than a triple-bridged assembly, especially for complexes
      with small M-O...O-Gd hinge angles. Our results show the crucial role of the Gd
      5d orbitals in the exchange interaction while the 6s orbital seems to have a
      negligible participation. The analysis of the atomic and orbital spin populations
      reveals that the presence of spin density in the Gd 5d orbital is mainly due to a
      spin polarization effect, while a delocalization mechanism from the 3d orbitals
      of the transition metal can be ruled out. We propose a numerical DFT approach
      using pseudopotentials to calculate the exchange coupling constants in four
      polynuclear first-row transition metal-Gd complexes. Despite the complexity of
      the studied systems, the numerical approach gives coupling constants in excellent
      agreement with the available experimental data and, in conjunction with exact
      diagonalization methods (or Monte Carlo simulations), it makes it possible to
      obtain theoretical estimates of the entropy change due to the
      magnetization/demagnetization process of the molecule.

PMID- 22640028
TI  - Relationship between ocular wavefront aberrations and refractive error in Chinese
      school children.
AB  - BACKGROUND: The relationship between ocular wavefront aberrations and refractive
      error in children's eyes remains controversial. The purpose of this study is to
      re-examine this relationship in Chinese school children under natural distance
      accommodation. METHODS: Ocular wavefront aberrations were measured in 86 Chinese
      children with spherical equivalent refraction (SER) between +0.5 D and -6.0 D and
      astigmatism less than -1.00 D. Wavefront aberrations were calculated using an
      objective method based on the Hartmann-Shack principle. Refractive error was
      obtained using a phoropter after cycloplegia. Subjects were categorised into
      three groups based on the mean SER: emmetropia (SER from -0.50 D to +0.50 D),
      mild myopia (SER greater than -0.50 D to -3.00 D) and moderate myopia (SER
      greater than -3.00 D to -6.00 D). Of the 86 participants, 22 were emmetropic, 43
      were mildly myopic and 21 were moderately myopic. The root mean square (RMS)
      values of higher-order aberrations, Zernike coefficients (third-, fourth- and
      fifth-order aberrations) and R(j) (the ratio of third-, fourth- or fifth-order
      aberrations to total higher-order aberrations) were compared across the three
      refractive groups. RESULTS: No significant correlations were found between the
      RMS values of total higher-order aberrations, third-order aberrations, fourth
      order aberrations, fifth-order aberrations, spherical aberration or coma and SER.
      No significant differences in the RMS values of total higher-order aberrations or
      R(j) were observed among the groups. The difference in fifth-order aberrations
      was statistically significant among the groups (p = 0.022); no other differences
      in higher-order aberration were found. Aside from C (3,1), no other differences
      were observed for Zernike coefficients. CONCLUSION: Ocular wavefront aberrations
      are similar among Chinese school children with different refractive errors under
      natural accommodation for a distance target. There is no evidence that myopes
      have a different amount of ocular higher-order aberrations than emmetropes.

PMID- 22640029
TI  - Carotenogenesis gene cluster and phytoene desaturase catalyzing both three- and
      four-step desaturations from  Rhodobacter azotoformans.
AB  - A carotenogenesis gene cluster from the purple nonsulfur photosynthetic bacterium
      Rhodobacter azotoformans CGMCC 6086 was cloned. A total of eight carotenogenesis
      genes ( crtA , crtI , crtB , tspO , crtC , crtD , crtE , and crtF ) were located
      in two separate regions within the genome, a 4.9 kb region containing four
      clustered genes of crtAIB - tspO and a 5.3 kb region containing four clustered
      genes of crtCDEF . The organization was unusual for a carotenogenesis gene
      cluster in purple photosynthetic bacteria. A gene encoding phytoene desaturase (
      CrtI ) from Rba. azotoformans was expressed in Escherichia coli. The recombinant
      CrtI could catalyze both three- and four-step desaturations of phytoene to
      produce neurosporene and lycopene, and the relative contents of neurosporene and
      lycopene formed by CrtI were approximately 23% and 75%, respectively. Even small
      amounts of five-step desaturated 3,4-didehydrolycopene could be produced by CrtI
      . This product pattern was novel because CrtI produced only neurosporene leading
      to spheroidene pathway in the cells of Rba. azotoformans. In the in vitro
      reaction, the relative content of lycopene in desaturated products increased from
      19.6% to 62.5% when phytoene reduced from 2.6 to 0.13 MUM. The results revealed
      that the product pattern of CrtI might be affected by the kinetics.

PMID- 22640030
TI  - The cost of child health inequalities in Aotearoa New Zealand: a preliminary
      scoping study.
AB  - BACKGROUND: Health inequalities have been extensively documented, internationally
      and in New Zealand. The cost of reducing health inequities is often perceived as
      high; however, recent international studies suggest the cost of "doing nothing"
      is itself significant. This study aimed to develop a preliminary estimate of the
      economic cost of health inequities between Maori (indigenous) and non-Maori
      children in New Zealand. METHODS: Standard quantitative epidemiological methods
      and "cost of illness" methodology were employed, within a Kaupapa Maori
      theoretical framework. Data were obtained from national data collections held by
      the New Zealand Health Information Service and other health sector agencies.
      RESULTS: Preliminary estimates suggest child health inequities between Maori and
      non-Maori in New Zealand are cost-saving to the health sector. However the
      societal costs are significant. A conservative "base case" scenario estimate is
      over $NZ62 million per year, while alternative costing methods yield larger costs
      of nearly $NZ200 million per annum. The total cost estimate is highly sensitive
      to the costing method used and Value of Statistical Life applied, as the cost of
      potentially avoidable deaths of Maori children is the major contributor to this
      estimate. CONCLUSIONS: This preliminary study suggests that health sector
      spending is skewed towards non-Maori children despite evidence of greater Maori
      need. Persistent child health inequities result in significant societal economic
      costs. Eliminating child health inequities, particularly in primary care access,
      could result in significant economic benefits for New Zealand. However, there are
      conceptual, ethical and methodological challenges in estimating the economic cost
      of child health inequities. Re-thinking of traditional economic frameworks and
      development of more appropriate methodologies is required.

PMID- 22640031
TI  - Perifosine plus lenalidomide and dexamethasone in relapsed and
      relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research
      Consortium study.
AB  - The combination of lenalidomide-dexamethasone is active in multiple myeloma (MM).
      Preclinical data showed that the Akt inhibitor, perifosine, sensitized MM cells
      to lenalidomide and dexamethasone, providing the rationale for this Phase I,
      multicentre, single-arm study to assess the safety and determine the maximum
      tolerated dose (MTD) of perifosine-lenalidomide-dexamethasone in relapsed and
      relapsed/refractory MM. Patients received escalating doses of perifosine 50-100
      mg daily and lenalidomide 15-25 mg once daily on days 1-21 of each 28-d cycle,
      plus dexamethasone 20-40 mg weekly thereafter, as indicated. Thirty-two patients
      were enrolled across four dose cohorts. MTD was not reached, with 31 patients
      evaluable for safety/tolerability. The most common all-causality grade 1-2
      adverse events were fatigue (48%) and diarrhoea (45%), and grade 3-4 neutropenia
      (26%), hypophosphataemia (23%), thrombocytopenia (16%), and leucopenia (13%).
      Among 30 evaluable patients, 73% (95% confidence interval, 57.5-89.2%) achieved a
      minimal response or better, including 50% with a partial response or better.
      Median progression-free survival was 10.8 months and median overall survival 30.6
      months. Response was associated with phospho-Akt in pharmacodynamic studies.
      Perifosine-lenalidomide-dexamethasone was well tolerated and demonstrated
      encouraging clinical activity in relapsed and relapsed/refractory MM.

PMID- 22640033
TI  - Remote effects of intermittent theta burst stimulation of the human pharyngeal
      motor system.
AB  - Intermittent theta burst stimulation (iTBS) is a novel, non-invasive form of
      brain stimulation capable of facilitating excitability of the human primary motor
      cortex with therapeutic potential in the treatment of neurological conditions,
      such as multiple sclerosis. The objectives of this study were to evaluate the
      effects of iTBS on cortical properties in the human pharyngeal motor system.
      Transcranial magnetic stimulation (TMS)-evoked pharyngeal motor responses were
      recorded via a swallowed intra-luminal catheter and used to assess motor cortical
      pathways to the pharynx in both hemispheres before and for up to 90 min after
      iTBS in 15 healthy adults (nine male/six female, 22-59 years old). Active/sham
      iTBS comprised 600 intermittent repetitive TMS pulses, delivered in a double
      blind pseudo-randomised order over each hemisphere on separate days at least 1
      week apart. Abductor pollicis brevis (APB) recordings were used as control.
      Hemispheric interventional data were compared with sham using repeated-measures
      anova. iTBS was delivered at an average intensity of 43+/-1% of stimulator
      output. Compared with sham, iTBS to the hemisphere with stronger pharyngeal
      projections induced increased responses only in the contralateral weaker
      projection 60-90 min post-iTBS (maximum 54+/-19%, P<=0.007), with no change in
      stronger hemisphere responses. By contrast, iTBS to weaker projections had no
      significant effects (P=0.39) on either hemisphere. APB responses similarly did
      not change significantly (P=0.78) across all study arms. We conclude that iTBS
      can induce remote changes in corticobulbar excitability. While further studies
      will clarify the extent of these changes, iTBS holds promise as a potential
      treatment for dysphagia after unilateral brain damage.

PMID- 22640032
TI  - The association of mental conditions with blood glucose levels in older adults
      with diabetes.
AB  - OBJECTIVES: People with diabetes must engage in several self-care activities to
      manage blood glucose; cognitive function and other affective disorders may affect
      self-care behaviors. We examined the executive function domain of cognition,
      depressive symptoms, and symptoms of generalized anxiety disorder (GAD) to
      determine which common mental conditions can co-occur with diabetes are
      associated with blood glucose levels. METHODS: We conducted a cross-sectional in
      person survey of 563 rural older adults (age 60 years or older) with diabetes
      that included African Americans, American Indians, and Whites from eight counties
      in south-central North Carolina. Hemoglobin A1C (A1C) was measured from a finger
      stick blood sample to assess blood glucose control. Executive function,
      depressive symptoms, and symptoms of GAD were assessed using established measures
      and scoring procedures. Separate multivariate linear regression models were used
      to examine the association of executive function, depressive symptoms, and
      symptoms of GAD with A1C. RESULTS: Adjusting for potential confounders including
      age, gender, education, ethnicity, marital status, history of stroke, heart
      disease, hypertension, diabetes knowledge, and duration of diabetes, executive
      function was significantly associated with A1C levels: every one-unit increase in
      executive function was associated with a 0.23 lower A1C value (p = 0.02).
      Symptoms of depression and GAD were not associated with A1C levels. CONCLUSIONS:
      Low executive function is potentially a barrier to self-care, the cornerstone of
      managing blood glucose levels. Training aids that compensate for cognitive
      impairments may be essential for achieving effective glucose control.

PMID- 22640035
TI  - Self-management strategies adopted by breast cancer survivors to improve their
      adherence to tamoxifen.

PMID- 22640034
TI  - Safety and efficacy of substituting nedaplatin after carboplatin hypersensitivity
      reactions in gynecologic malignancies.
AB  - AIM: Repeated treatment with carboplatin increases the incidence of
      hypersensitivity reactions. Current managements for carboplatin hypersensitivity
      reactions involve premedication, desensitization, and replacing agents. However,
      preventive effects for recurrent reactions by the former two methods are still
      limited, and substituting non-platinum agent can attenuate efficacy against
      platinum-sensitive diseases. The aim of this study was to evaluate the safety and
      efficacy of substituting nedaplatin, another platinum compound, as a strategy to
      deal with carboplatin hypersensitivity reactions in gynecologic cancers. MATERIAL
      AND METHODS: Patients who experienced carboplatin hypersensitivity reactions and
      subsequently switched to nedaplatin between 2001 and 2009 were identified through
      our database. The incidence and severity of nedaplatin hypersensitivity were
      examined. Response to nedaplatin therapy was evaluated according to Response
      Evaluation Criteria in Solid Tumors (RECIST) and serum CA-125 levels. RESULTS:  
      Forty-six of 570 patients (8.1%) experienced carboplatin hypersensitivity
      reactions, and the increased cycle numbers of carboplatin-based regimens
      correlated with the high incidence of hypersensitivity (<=6, 0.9% vs >=7, 19.2%).
      Of these 46 patients, 38 subsequently switched to nedaplatin-based regimens
      (ovarian, tubal or peritoneal carcinoma, 30; endometrial carcinoma, 6; cervical
      carcinoma, 2). Three of the 38 patients (7.9%) eventually developed
      hypersensitivity against nedaplatin, and all their reactions were grade 2. The
      response rate to nedaplatin therapy among 32 evaluable patients was 31.3%.
      CONCLUSION: Replacing carboplatin with nedaplatin provided a safe and efficacious
      approach to manage carboplatin hypersensitivity. To the authors' knowledge, this
      study is the first to indicate the usefulness of nedaplatin after carboplatin
      hypersensitivity reactions. Further evaluations are warranted to confirm our
      finding.

PMID- 22640036
TI  - Controlled and continuous release ocular drug delivery systems: pros and cons.
AB  - Topical ocular drug administration is the most preferred route for treating
      conditions affecting the surface of the eye as well as anterior segment diseases;
      this is mainly due to the rapid and localised drug action and patient
      acceptability. However, the ocular bioavailability is typically less than 5% from
      conventional ophthalmic dosage forms such as eye drops. This is mainly due to the
      unique anatomical and physiological features of the eye. One of the effective
      pharmaceutical approaches is to provide a controlled and continuous drug release
      to the surface of the eye to compensate drug loss by nasolacrimal drainage and
      non-productive absorption of the topically applied drug. This review provides a
      critical appraisal (advantages and drawbacks) of the different drug delivery
      strategies that provides controlled and continuous drug supply to the surface of
      the eye; it covers research conducted over the past three decades.

PMID- 22640038
TI  - Polymers and drug delivery systems.
AB  - In the treatment of health related dysfunctions, it is desirable that the drug
      reaches its site of action at a particular concentration and that this
      therapeutic dose range remains constant over a sufficiently long period of time
      to alter the process. However, the action of pharmaceutical agents is limited by
      various factors, including their degradation, their interaction with other cells,
      and their incapacity to penetrate tissues as a result of their chemical nature.
      For these reasons, new formulations are being studied to achieve a greater
      pharmacological response; among these, polymeric systems of drug carriers are of
      high interest. These systems are an appropriate tool for time- and distribution
      controlled drug delivery. The mechanisms involved in controlled release require
      polymers with a variety of physicochemical properties. Thus, several types of
      polymers have been tested as potential drug delivery systems, including nano- and
      micro-particles, dendrimers, nano- and micro-spheres, capsosomes, and micelles.
      In all these systems, drugs can be encapsulated or conjugated in polymer
      matrices. These polymeric systems have been used for a range of treatments for
      antineoplastic activity, bacterial infections and inflammatory processes, in
      addition to vaccines.

PMID- 22640037
TI  - Formulation and in vivo hypoglycemic effect of glipizide solid dispersion.
AB  - The present study was carried out with a view to enhance dissolution rate of
      poorly water-soluble drug glipizide (GZ) (BCS class II) using polyethylene glycol
      (PEG) 6000, PEG 8000 and poloxamer (PXM) 188 as carriers. Solid dispersions (SDs)
      were prepared by melting method using different ratios of glipizide to carriers.
      Phase solubility study was conducted to evaluate the effect of carrier on aqueous
      solubility of glipizide. SD was optimized by drug content estimation and in vitro
      dissolution study and optimised SD was subjected to bulk characterization,
      Scanning electron microscopy (SEM), Fourier transformation infrared spectroscopy
      (FTIR), Differential scanning calorimetry (DSC) and X-ray diffraction study
      (XRD). Preclinical study was performed in mice to study the decrease in blood
      glucose level from prepared SD compared with pure drug. Due to high solubility
      and drug release, PXM 188 in weight ratio of 1:2 was optimized. Decrease in blood
      glucose level in mice from SD was significantly higher (p < 0.05) compared to
      pure glipizide. Thus, solid dispersion technique can be successfully used for the
      improvement of the dissolution profile of GZ.

PMID- 22640164
TI  - Juvenile xanthogranulomas of the nervous system: A report of two cases and review
      of the literature.
AB  - Juvenile xanthogranulomas (JXG) are uncommon non-Langerhans cell histiocytic
      proliferations which arise most often in children. While most cases present as
      solitary cutaneous lesions, occasional cases involve extracutaneous sites. Rare
      examples of JXGs have been reported involving all levels of the neuroaxis. We
      present two cases of JXGs involving the nervous system, and review the
      literature. The first patient was a 14-year-old female with headaches and a mass
      involving the left trigeminal nerve; pathologic examination showed a JXG. At 11
      months follow-up, after administration of systemic chemotherapy, the patient
      remained stable with residual tumor. The second patient was a 15-year-old female
      with leg weakness and numbness, who underwent complete surgical resection of a
      dural JXG. At eight months follow-up, she showed no evidence of tumor, and was
      able to walk without difficulty. Review of the literature revealed 38 previously
      published reports of JXGs involving the nervous system. The CNS was involved in
      the majority (75%) of cases. The clinical characteristics of JXGs arising in the
      CNS varied significantly from cases in the peripheral nervous system (PNS); CNS
      tumors occurred in younger patients, more often males, and were more likely to be
      associated with concurrent cutaneous and extra-nervous systemic lesions. The
      clinical outcomes were similar for CNS and PNS lesions, with the caveat that all
      three lethal JXGs occurred in the CNS. The clinical and radiologic presentation
      of JXGs is nonspecific, thus necessitating biopsy and pathologic examination to
      arrive at the diagnosis. The pathologic differential diagnosis includes a
      heterogeneous group of histiocytic proliferations; immunostaining for histiocytic
      markers CD68, factor XIIIa, and Fascin, and the absence of Birbeck granules and
      CD1a immunoexpression suggests the diagnosis of JXG. In many cases, total
      surgical resection is curative. However, some cases will require additional
      chemotherapy and/or radiotherapy.

PMID- 22640039
TI  - The inducible effect of LBP on maturation of dendritic cells and the related
      immune signaling pathways in hepatocellular carcinoma (HCC).
AB  - OBJECTIVE: To investigate the effect of LBP on differentiation and maturation of
      healthy human peripheral blood-derived dendritic cells cultured in different
      tumor microenvironment in vitro, and discuss the molecular and immunological
      mechanisms of LBP in treatment of tumor. METHODS: In this study, we procured the
      peripheral blood-derived dendritic cells precursor cell by the Density gradient
      centrifugation method, and used the tumor-cell supernatant to prepare conditioned
      medium. The GM-CSF and IL-4 induced DCs precursor cell differentiation to DCs,
      the TNF-alpha promoted the immature DCs developed to mature DCs. In this way, we
      detected the influence of LBP on the expressions of surface molecules of DCs
      cultured in different environments, and especially on the role of related
      immunity and NF-kappaB activity. RESULTS: In LBP-treated group, the molecular
      phenotype of DCs, its capacity to stimulate allogeneic lymphocyte proliferation,
      and the levels of IL-12p70 and IFN-gamma secretion were higher than the untreated
      group (p < 0.05), with statistical significance. Meanwhile the expression of NF
      kappaB of the DCs in the medium treated by the LBP was higher than the untreated
      group (p < 0.05), also with statistical significance. Between the two different
      tumor microenvironment groups, the cell nucleus protein NF-kappaB expression is
      obviously different, the hepG2.2.15 group higher than the hepG2 group.
      CONCLUSION: LBP could increase the expression of the phenotype of DCs, the
      secretion of IL-12p70 and IFN-gamma in MLR, and enhance the NF-kappaB expression,
      especially in the virus-related group, suggesting LBP plays the anti-tumor role
      stronger in the virus-related environment and this phenomenon correlates with the
      NF-kappaB signaling pathway.

PMID- 22640165
TI  - The first national pressure ulcer prevalence survey in county council and
      municipality settings in Sweden.
AB  - AIM: To report data from the first national pressure ulcer prevalence survey in
      Sweden on prevalence, pressure ulcer categories, locations and preventive
      interventions for persons at risk for developing pressure ulcers. METHODS: A
      cross-sectional research design was used in a total sample of 35,058 persons in
      hospitals and nursing homes. The methodology used was that recommended by the
      European Pressure Ulcer Advisory Panel. RESULTS: The prevalence of pressure
      ulcers was 16.6% in hospitals and 14.5% in nursing homes. Many persons at risk
      for developing pressure ulcers did not receive a pressure-reducing mattress (23.3
      27.9%) or planned repositioning in bed (50.2-57.5%). CONCLUSIONS: Despite great
      effort on the national level to encourage the prevention of pressure ulcers, the
      prevalence is high. Public reporting and benchmarking are now available, evidence
      based guidelines have been disseminated and national goals have been set.
      Strategies for implementing practices outlined in the guidelines, meeting goals
      and changing attitudes must be further developed.

PMID- 22640167
TI  - Bowel-associated dermatosis-arthritis syndrome: another cutaneous manifestation
      of inflammatory intestinal disease.

PMID- 22640166
TI  - Persistent tumor cells in bone marrow of non-metastatic breast cancer patients
      after primary surgery are associated with inferior outcome.
AB  - BACKGROUND: To investigate the prognostic significance of disseminated tumor
      cells (DTCs) in bone marrow (BM) from non-metastatic breast cancer patients
      before and after surgery. METHODS: Patients with non-metastatic breast cancer
      were consecutively recruited to this project during the years 1998-2000. Real
      time RT-PCR quantification of a DTC multimarker panel consisting of cytokeratin
      19, mammaglobin A and TWIST1 mRNA was performed in BM samples obtained from 154
      patients three weeks (BM2) and/or six months after surgery (BM3). The results
      were compared to previously published data from pre-operative BM analyses for the
      same patients. RESULTS: DTCs were identified in post-operative BM samples (BM2
      and/or BM3) from 23 (15%) of the 154 patients investigated. During a median
      follow-up of 98 months, 10 (44%) of these patients experienced systemic relapse
      as compared to 16 (12%) of 131 DTC-negative patients. Kaplan-Meier estimates of
      systemic recurrence-free- and breast-cancer specific survival demonstrated
      significantly shorter survival for patients with persistent DTCs in BM after
      surgery (p<=0.001). By multivariate Cox regression analyses, persistent DTCs
      after surgery was an independent predictor of both systemic recurrence-free- (HR
      = 5.4, p < 0.001) and breast-cancer specific survival (HR = 5.3, p < 0.001).
      Furthermore, the prognostic value of DTCs in BM was similar for pre- and post
      surgery samples. However, patients with DTCs both before and after surgery (BM1
      and BM2/3) had a particularly poor prognosis (systemic recurrence-free survival:
      HR = 7.2, p < 0.0001 and breast-cancer specific survival: HR = 8.0, p < 0.0001).
      CONCLUSIONS: Detection of persistent DTCs in BM samples obtained after surgery
      identified non-metastatic breast cancer patients at high risk for systemic
      relapse, and with reduced breast-cancer specific survival. Furthermore, patients
      with positive DTC status both before and after surgery had a particularly poor
      prognosis.

PMID- 22640169
TI  - Real time three-dimensional transesophageal echocardiography in the evaluation of
      two cases of rare mitral valve tumors.

PMID- 22640168
TI  - Evidence for an adaptation in ROS scavenging systems in human testicular
      peritubular cells from infertility patients.
AB  - Fibrosis, increased amounts of immune cells and expression of COX-2 in the testes
      of infertility patients provide circumstantial evidence for a specific testicular
      milieu, in which reactive oxygen species (ROS) could be increased. If ROS level
      increase and/or ROS scavengers decrease, the resulting testicular oxidative
      stress may contribute to human male infertility. Primary peritubular cells of the
      human testis, from men with normal spermatogenesis (HTPCs) and infertile patients
      (HTPC-Fs), previously allowed us to identify an end product of COX-2 action, a
      prostaglandin derivative (15dPGJ2), which acts via ROS to alter the phenotype of
      peritubular cells, at least in vitro. Using testicular biopsies we now found
      15dPGJ2 in patients and hence we started exploring the ROS scavenger systems of
      the human testis. This system includes catalase, DJ-1, peroxiredoxin 1, SOD 1 and
      2, glutathione-S-transferase and HMOX-1, which were identified by RT
      PCR/sequencing in HTPCs and HTPC-Fs and whole testes. Catalase, DJ-1,
      peroxiredoxin 1 and SOD 2 were also detected by Western blots and in part by
      immunohistochemistry in testicular samples. Western blots of cultured cells
      further revealed that catalase levels, but not peroxiredoxin 1, SOD 2 or DJ-1
      levels, are significantly higher in HTPC-Fs than in HTPCs. This particular
      difference is correlated with the improved ability of HTPC-Fs to handle ROS,
      which became evident when cells were exposed to 100 MUm H(2)O(2). H(2)O(2)
      induced stronger responses in HTPCs than in HTPC-Fs, which correlates with the
      lower level of the H(2)O(2)-degrading defence enzyme catalase in HTPCs. The
      results provide evidence for an adaptation to elevated ROS levels, which must
      have occurred in vivo and which persist in vitro in HTPC-Fs. Thus, in infertile
      men with impaired spermatogenesis elevated ROS levels likely exist, at least in
      the tubular wall.

PMID- 22640170
TI  - Systematic investigation of benzodithiophene- and diketopyrrolopyrrole-based low
      bandgap polymers designed for single junction and tandem polymer solar cells.
AB  - The tandem solar cell architecture is an effective way to harvest a broader part
      of the solar spectrum and make better use of the photonic energy than the single
      junction cell. Here, we present the design, synthesis, and characterization of a
      series of new low bandgap polymers specifically for tandem polymer solar cells.
      These polymers have a backbone based on the benzodithiophene (BDT) and
      diketopyrrolopyrrole (DPP) units. Alkylthienyl and alkylphenyl moieties were
      incorporated onto the BDT unit to form BDTT and BDTP units, respectively; a furan
      moiety was incorporated onto the DPP unit in place of thiophene to form the FDPP
      unit. Low bandgap polymers (bandgap = 1.4-1.5 eV) were prepared using BDTT, BDTP,
      FDPP, and DPP units via Stille-coupling polymerization. These structural
      modifications lead to polymers with different optical, electrochemical, and
      electronic properties. Single junction solar cells were fabricated, and the
      polymer:PC(71)BM active layer morphology was optimized by adding 1,8-diiodooctane
      (DIO) as an additive. In the single-layer photovoltaic device, they showed power
      conversion efficiencies (PCEs) of 3-6%. When the polymers were applied in tandem
      solar cells, PCEs over 8% were reached, demonstrating their great potential for
      high efficiency tandem polymer solar cells.

PMID- 22640171
TI  - An efficient and reproducible method for transformation of genetically
      recalcitrant bifidobacteria.
AB  - This study describes an efficient transformation system for the introduction of
      plasmid DNA into Bifidobacterium bifidum PRL2010 and Bifidobacterium asteroides
      PRL2011, for which to the best of our knowledge no transformation data have been
      reported previously. The method is based on electroporation of bifidobacterial
      cells, which were made competent by an optimized methodology based on varying
      media and growth conditions. Furthermore, the transformation protocol was applied
      in order to design a PRL2010-derivative, which carries antibiotic resistance
      against chloramphenicol and which was used to monitor PRL2010 colonization in a
      murine model.

PMID- 22640173
TI  - Coping focus counselling in mental health nursing.
AB  - The aim of this paper was to describe a newly-developed system of mental health
      nurse counselling (coping focus counselling (CFC)) for people with serious and
      complex mental health needs. The system is based on the recovery alliance theory
      (RAT) of mental health nursing. The paper identifies shortcomings in current
      practices in psychotherapy and counselling in the exclusive use of techniques
      from a single approach, for example, cognitive behaviour therapy, client-centred
      therapy, attachment theory, or Gestalt theory. It also discusses the opposite
      dangers of the use of many techniques from different approaches, without a clear
      rationale for their selection. CFC was developed to avoid these practices. It
      accommodates the selective use of techniques from different approaches.
      Techniques selected are viewed as deriving their meanings from the theoretical
      framework into which they are assimilated, namely RAT, and no longer take the
      same meaning from the theory from which they originated. Central to this
      integrative process is the use of the concept of coping. Other distinguishing
      features of CFC are the use of everyday language in using the system and the
      reaffirmation of the nurse-client relationship within a working alliance as the
      basis in which the CFC operates.

PMID- 22640172
TI  - Mechanisms of constitutive and ATP-evoked ATP release in neonatal mouse olfactory
      epithelium.
AB  - BACKGROUND: ATP is an extracellular signaling molecule with many ascribed
      functions in sensory systems, including the olfactory epithelium. The
      mechanism(s) by which ATP is released in the olfactory epithelium has not been
      investigated. Quantitative luciferin-luciferase assays were used to monitor ATP
      release, and confocal imaging of the fluorescent ATP marker quinacrine was used
      to monitor ATP release via exocytosis in Swiss Webster mouse neonatal olfactory
      epithelial slices. RESULTS: Under control conditions, constitutive release of ATP
      occurs via exocytosis, hemichannels and ABC transporters and is inhibited by
      vesicular fusion inhibitor Clostridium difficile toxin A and hemichannel and ABC
      transporter inhibitor probenecid. Constitutive ATP release is negatively
      regulated by the ATP breakdown product ADP through activation of P2Y receptors,
      likely via the cAMP/PKA pathway. In vivo studies indicate that constitutive ATP
      may play a role in neuronal homeostasis as inhibition of exocytosis inhibited
      normal proliferation in the OE. ATP-evoked ATP release is also present in mouse
      neonatal OE, triggered by several ionotropic P2X purinergic receptor agonists
      (ATP, alphabetaMeATP and Bz-ATP) and a G protein-coupled P2Y receptor agonist
      (UTP). Calcium imaging of P2X2-transfected HEK293 "biosensor" cells confirmed the
      presence of evoked ATP release. Following purinergic receptor stimulation, ATP is
      released via calcium-dependent exocytosis, activated P2X1,7 receptors, activated
      P2X7 receptors that form a complex with pannexin channels, or ABC transporters.
      The ATP-evoked ATP release is inhibited by the purinergic receptor inhibitor
      PPADS, Clostridium difficile toxin A and two inhibitors of pannexin channels:
      probenecid and carbenoxolone. CONCLUSIONS: The constitutive release of ATP might
      be involved in normal cell turn-over or modulation of odorant sensitivity in
      physiological conditions. Given the growth-promoting effects of ATP, ATP-evoked
      ATP release following injury could lead to progenitor cell proliferation,
      differentiation and regeneration. Thus, understanding mechanisms of ATP release
      is of paramount importance to improve our knowledge about tissue homeostasis and
      post-injury neuroregeneration. It will lead to development of treatments to
      restore loss of smell and, when transposed to the central nervous system, improve
      recovery following central nervous system injury.

PMID- 22640175
TI  - Pulmonary artery extension of uterine leiomyoma.
AB  - Intravenous leiomyomatosis is a rare tumor arising either from a uterine
      leiomyoma or from uterine vessel walls with extension into venous channels.
      Although intravenous leiomyomatosis is considered histologically "benign,"
      intrusion to the cardiac chambers is almost malignant given its possibility for
      destruction of heart valves, extending into the pulmonary vasculature, and
      embolizing. We report a patient with an intravenous leiomyomatosis progressing
      through the left iliac vein, along the entire vena cava up to the right cardiac
      chambers and branches of pulmonary artery (PA), and review the literature on this
      subject.

PMID- 22640174
TI  - Cost utility of tumour necrosis factor-alpha inhibitors for rheumatoid arthritis:
      an application of Bayesian methods for evidence synthesis in a Markov model.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that
      affects approximately 1.5 million people in the US. Tumour necrosis factor (TNF)
      alpha inhibitors have been shown to effectively treat and maintain remission in
      patients with moderately to severely active RA compared with conventional agents.
      The high acquisition cost of TNF-alpha inhibitors prohibits access, which
      mandates economic investigations into their affordability. The lack of head-to
      head comparisons between these agents makes it difficult to determine which agent
      is the most cost effective. OBJECTIVE: This study aimed to determine which TNF
      alpha inhibitor was the most cost-effective agent for the treatment of moderately
      to severely active RA from the US healthcare payer's perspective. METHODS: A
      Markov model was constructed to analyse the cost utility of five TNF-alpha
      inhibitors (in combination with methotrexate [+MTX]) versus MTX monotherapy using
      Bayesian methods for evidence synthesis. The model had a cycle length of 3 months
      and an overall time horizon of 5 years. Transition probabilities and utility
      scores were based on published studies. Total direct costs were adjusted to year
      2009 $US using the medical component of the Consumer Price Index. All costs and
      QALYs were discounted at a rate of 3% per year. Patient response to the different
      strategies was determined by the American College of Rheumatology (ACR)50
      criteria. One-way and probabilistic sensitivity analyses (PSAs) were performed to
      test the robustness of the base-case scenario. The base-case scenario was changed
      to ACR20 criteria (scenario 1) and ACR70 criteria (scenario 2) to determine the
      model's robustness. Cost-effectiveness acceptability curves and cost
      effectiveness frontiers were used to estimate the cost-effectiveness probability
      of each treatment strategy. A willingness-to-pay (WTP) threshold was defined as
      three times the US GDP per capita ($US139,143 per additional QALY gained).
      Primary results were presented as incremental cost-effective ratios (ICERs).
      RESULTS: Etanercept+MTX was the most cost-effective treatment strategy in the
      base-case scenario up to a WTP threshold of $US2 185,497 per QALY gained. At a
      WTP threshold of greater than $US2 185,497 per QALY gained, certolizumab+MTX was
      the most cost-effective treatment strategy. One-way analyses showed that the base
      case scenario was sensitive to the probability of achieving ACR50 criteria for
      MTX and each TNF-alpha inhibitor, and changes in the utility score for patients
      who achieved the ACR50 criteria. With the exception of infliximab, all of the TNF
      alpha inhibitors were sensitive to drug cost per cycle. In the scenario analyses,
      certolizumab+MTX was a dominant treatment strategy using ACR20 criteria, but
      etanercept+MTX was a dominant treatment strategy using ACR70 criteria.
      CONCLUSIONS: Etanercept+MTX was a cost-effective treatment strategy in the base
      case scenario; however, the model was sensitive to parameter uncertainties and
      ACR response criteria. Although Bayesian methods were used to determine
      transition probabilities, future studies will need to focus on head-to-head
      comparisons of multiple TNF-alpha inhibitors to provide valid comparisons.

PMID- 22640176
TI  - Triage of frail elderly with reduced exercise tolerance in primary care (TREE). A
      clustered randomized diagnostic study.
AB  - BACKGROUND: Exercise reduced tolerance and breathlessness are common in the
      elderly and can result in substantial loss in functionality and health related
      quality of life. Heart failure (HF) and chronic obstructive pulmonary disease
      (COPD) are common underlying causes, but can be difficult to disentangle due to
      overlap in symptomatology. In addition, other potential causes such as obesity,
      anaemia, renal dysfunction and thyroid disorders may be involved.We aim to assess
      whether screening of frail elderly with reduced exercise tolerance leads to high
      detection rates of HF, COPD, or alternative diagnoses, and whether detection of
      these diseases would result in changes in patient management and increase in both
      functionality and quality of life. METHODS/DESIGN: A cluster randomized
      diagnostic trial. Primary care practices are randomized to the diagnostic
      treatment strategy (screening) or care as usual. PATIENT POPULATION: Frail
      (defined as having three or more chronic or vitality threatening diseases and/or
      receiving five or more drugs chronically during the last year) community-dwelling
      persons aged 65 years and older selected from the electronic medical files of the
      participating general practitioners. Those with reduced exercise tolerance or
      moderate to severe dyspnoea (>=2 score on the Medical Research Counsel dyspnoea
      scale) are included in the study.The diagnostic screening in the intervention
      group includes history taking, physical examination, electrocardiography,
      spirometry, blood tests, and echocardiography. Subsequently, participants with
      new diagnoses will be managed according to clinical guidelines. Participants in
      the control arm receive care as usual. All participants fill out health status
      and other relevant questionnaires at baseline and after 6 months of follow-up.
      DISCUSSION: This study will generate information on the yield of screening for
      previously unrecognized HF, COPD and other chronic diseases in frail elderly with
      reduced exercise tolerance and/or exercise induced dyspnoea. The cluster
      randomized comparison will reveal whether this yield will result in subsequent
      improvements in functional health and/or health related quality of life. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01148719.

PMID- 22640178
TI  - Plate fixation or intramedullary fixation of humeral shaft fractures--an update.

PMID- 22640177
TI  - Stressful life events and daily stressors affect awakening cortisol level in
      midlife mothers of individuals with autism spectrum disorders.
AB  - OBJECTIVES: The current study examines the awakening cortisol level in midlife
      mothers (M = 51.4 years old, SD = 8.4) of individuals (M = 22.1 years old, SD =
      7.1) with autism spectrum disorders (ASD) under stressful conditions that are not
      specific to their son or daughter's ASD symptoms. METHODS: In addition to
      completing a set of questionnaires and in-home interviews, 82 mothers from the
      Adolescents and Adults with Autism Study (AAA) participated in a Daily Diary
      Study. RESULTS: Findings from the multilevel models indicated that mothers who
      previously were exposed to no negative life events in the previous period had an
      increased awakening cortisol level on days following a greater number and more
      severe stressors, a normative stress response. In contrast, we observed a flatter
      cortisol level of daily stressors in mothers who experienced a greater number of
      negative life events in the previous period. CONCLUSION: These findings highlight
      the sustained toll that global and everyday stressors have on awakening cortisol
      level of midlife and aging mothers of individuals with ASD.

PMID- 22640179
TI  - Intramedullary knee spacer in 2-stage revision knee surgery with segmental bone
      loss: a technical note involving 6 cases.

PMID- 22640181
TI  - Multidrug-resistant organisms, wounds and topical antimicrobial protection.
AB  - Multidrug-resistant organisms (MDROs) are increasingly implicated in both acute
      and chronic wound infections. The limited therapeutic options are further
      compromised by the fact that wound bacteria often co-exist within a biofilm
      community which enhances bacterial tolerance to antibiotics. As a consequence,
      topical antiseptics may be an important consideration for minimising the
      opportunity for wound infections involving MDROs. The objective of this research
      was to investigate the antimicrobial activity of a silver-containing gelling
      fibre dressing against a variety of MDROs in free-living and biofilm states,
      using stringent in vitro models designed to simulate a variety of wound
      conditions. MDROs included Acinetobacter baumannii, community-associated
      methicillin-resistant Staphylococcus aureus, and extended-spectrum beta-lactamase
      producing bacteria. Clostridium difficile was also included in the study because
      it carries many of the characteristics seen in MDROs and evidence of multidrug
      resistance is emerging. Sustained in vitro antimicrobial activity of the silver
      containing dressing was shown against 10 MDROs in a simulated wound fluid over 7
      days, and inhibitory and bactericidal effects against both free-living and
      biofilm phenotypes were also consistently shown in simulated colonised wound
      surface models. The in vitro data support consideration of the silver-containing
      gelling fibre dressing as part of a protocol of care in the management of wounds
      colonised or infected with MDROs.

PMID- 22640180
TI  - Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy
      for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem
      cell support: still very long survival but late relapses do occur.
AB  - Mantle cell lymphoma (MCL) is a heterogenic non-Hodgkin lymphoma entity, with a
      median survival of about 5 years. In 2008 we reported the early - based on the
      median observation time of 4 years - results of the Nordic Lymphoma Group MCL2
      study of frontline intensive induction immunochemotherapy and autologous stem
      cell transplantation (ASCT), with more than 60% event-free survival at 5 years,
      and no subsequent relapses reported. Here we present an update after a median
      observation time of 6.5 years. The overall results are still excellent, with
      median overall survival and response duration longer than 10 years, and a median
      event-free survival of 7.4 years. However, six patients have now progressed later
      than 5 years after end of treatment. The international MCL Prognostic Index
      (MIPI) and Ki-67-expression were the only independent prognostic factors.
      Subdivided by the MIPI-Biological Index (MIPI + Ki-67, MIPI-B), more than 70% of
      patients with low-intermediate MIPI-B were alive at 10 years, but only 23% of the
      patients with high MIPI-B. These results, although highly encouraging regarding
      the majority of the patients, underline the need of a risk-adapted treatment
      strategy for MCL. The study was registered at www.isrctn.org as ISRCTN 87866680.

PMID- 22640182
TI  - Three-dimensional conformal brachytherapy boost in locally recurrent or residual
      cervical carcinoma: does it impact clinical outcome?
AB  - AIM: To analyze the influence of computed tomography (CT)-guided 3D conformal
      interstitial brachytherapy (3D-IBT) boost for better coverage of target volumes
      and study the diametric impact to organ at risk in patients with post-surgery
      recurrent and residual cervical cancer. MATERIAL AND METHODS: Fourteen
      consecutive patients with recurrent or residual cervical cancer who were treated
      with interstitial brachytherapy as a boost were included in the study. All
      patients received 50.4 Gy external radiation (EBRT) to whole pelvis with
      conformal technique to reduce the dose to bowel. The clinical target volume (CTV)
      and organs at risk were contoured on CT scan with gold seeds being a surrogate
      marker of initial tumor extent implanted before commencing treatment. The median
      dose of prescription was 10.5-12Gy in 3 fractions. Dose volume histogram was
      calculated to evaluate the dose that covers 100% and 90% of the target volume and
      dose to the bladder, rectum and bowel (2 mL, 1 mL volume). RESULTS:   The median
      follow-up was 12 months (range 6-18). The doses to CTV (D90, D100) ranged from
      1141 to 2014 cGy, and 585 to 969 cGy, respectively. The mean cumulative 2-mL
      rectal, bladder and bowel doses were 66.70, 73.15 and 61.01Gy, respectively.
      Rectal toxicity of grade 2 or more had a strong correlation with the dose
      delivered (Spearman's correlation, 0.950). The local control rate at one year was
      92% with failure seen in one patient only. CONCLUSION: Conformal EBRT
      supplemented with 3D-IBT seems to be a practical and appropriate approach to give
      the most optimal therapeutic benefit with the least side-effects in postoperative
      recurrent and residual cervical cancer patients.

PMID- 22640183
TI  - Role of emmprin in endometrial cancer.
AB  - BACKGROUND: Extracellular matrix metalloproteinase inducer (Emmprin/CD147) is a
      transmembrane glycoprotein that belongs to the immunoglobulin superfamily.
      Enriched on the surface of many tumor cells, emmprin promotes tumor growth,
      invasion, metastasis and angiogenesis. We evaluated the clinical importance of
      emmprin and investigated its role in endometrial cancer. METHODS: Emmprin
      expression was examined in uterine normal endometrium, endometrial hyperplasia
      and cancer specimens by immunohistochemistry. In addition, the biological
      functions and inhibitory effects of an emmprin knockdown were investigated in HEC
      50B and KLE endometrial cancer cell lines. RESULTS: The levels of emmprin
      expression were significantly increased in the endometrial cancer specimens
      compared with the normal endometrium and endometrial hyperplasia specimens (p <
      0.05). The disease-free survival (DFS) and overall survival (OS) rates of
      patients with high emmprin expression were significantly higher than those of
      patients with low emmprin expression (DFS: p < 0.001; OS: p < 0.001). Emmprin
      knockdown by the siRNA led to cell proliferation, migration and invasion through
      TGF-beta, EGF, NF-kappaB, VEGF, MMP-2, and MMP-9 expression, which in turn
      resulted in increased levels of E-cadherin and reduced levels of Vimentin and
      Snail in endometrial cancer. CONCLUSIONS: The present findings suggest that low
      emmprin expression might be a predictor of favorable prognosis in endometrial
      cancer patients, and that emmprin may represent a potential therapeutic target
      for endometrial cancer.

PMID- 22640219
TI  - Viral encephalitis: current treatments and future perspectives.
AB  - Several viruses may cause central nervous system infections that lead to a broad
      range of clinical manifestations. The course of the viral encephalitis can be
      acute, sub acute, or chronic. Some viruses have the ability to enter into the
      brain and cause direct injury, while others activate inflammatory cells that
      attack the central nervous system (CNS) secondarily. Some types of viral
      encephalitis occur in previously healthy individuals, while others affect
      immunocompromised patients. The epidemiology of viral encephalitis has undergone
      changes in recent years. Factors such as evolving lifestyles and ecological
      changes have had a considerable impact on the epidemiology of some types of viral
      encephalitis. The result is a change in the etiology spectrum of viral
      encephalitis, with new types of encephalitis arising or returning from time to
      time. Many scientific achievements in neuroimaging, molecular diagnosis,
      antiviral therapy, immunomodulatory treatments, and neurointensive care have
      allowed more precise and earlier diagnoses and more efficient treatments,
      resulting in improved outcomes. Despite these advances, there is still
      considerable morbidity and mortality related to these disorders. This aim of this
      article is to review the current knowledge of the current drugs used in the
      management of the most important viral encephalitis, focusing on the mechanisms
      of action, efficacy, and side effects of the drugs. In addition, future
      perspectives in this area will be addressed. Despite the technological advances,
      much effort has yet to be undertaken to reduce the impact of these potentially
      devastating diseases.

PMID- 22640220
TI  - Melatonin and synthetic melatonergic agonists: actions and metabolism in the
      central nervous system.
AB  - The CNS is both source and target of melatonin. This methoxyindole formed in the
      pineal gland is also produced in other CNS regions and additionally enters the
      brain by uptake from the circulation as well as via the pineal recess. The
      mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN), not only
      controls the pineal, but also receives a feedback information on darkness. Two G
      protein-coupled melatonin receptors, MT1 and MT2, are responsible for the
      transduction of many melatonergic actions. High receptor densities are especially
      found in the SCN, but their presence at lower expression levels in other areas is
      functionally important. Various metabolites and analogs are formed in the CNS,
      such as N-acetylserotonin, 5-methoxytryptamine, 5-methoxytryptophol, 5
      methoxylated kynuramines, and even 6-sulfatoxymelatonin. The chronobiological
      effects of melatonin go beyond the resetting of a single circadian oscillator.
      They contribute to phase relationships between oscillatory subsets and are
      required for robust rhythm amplitudes. CNS effects of melatonin comprise sleep
      initiation, antiexcitatory, antiepileptic, antinociceptive, anxiolytic,
      proneurotrophic, antiinflammatory, antioxidant and other neuroprotective actions.
      The role as a sleep-promoting compound, which is limited by its short half-life
      in the circulation, has led to the development of controlled-release formulations
      and of various synthetic agonists, such as ramelteon, agomelatine, tasimelteon,
      TIK-301, UCM765 and UCM924. Their differences concerning receptor affinities,
      preferences for receptor subtypes, and pharmacokinetics are discussed, as well as
      additional antidepressive actions of agomelatine and TIK-301 based on properties
      as antagonists of the serotonergic 5-HT2C receptor. Indirect antidepressive
      effects by melatonergic drugs are largely explained by circadian readjustments.

PMID- 22640221
TI  - Stability, disposition, and penetration of catalytic antioxidants Mn-porphyrin
      and Mn-salen and of methylprednisolone in spinal cord injury.
AB  - This study measured the time courses of concentration changes following
      administration of the catalytic antioxidants Mn (III) tetrakis (4-benzoic acid)
      porphyrin (MnTBAP) and Mn (III) 3-methoxy N, N' bis (salicyclidene)
      ethylenediamine chloride (EUK-134) in blood and cerebrospinal fluid (CSF) of rats
      with a spinal cord injury (SCI) and sham controls. Parallel measurements were
      made for methylprednisolone, the only drug presently used clinically for treating
      SCI. The time courses kinetically characterized the agents in their stability,
      disposition, and ability to penetrate the blood-spinal cord barrier (BSB). In
      both the SCI and control groups, MnTBAP was stable in CSF and in blood across the
      collection periods (10 h and 24 h, respectively) following administration. In the
      blood, [EUK-134] and [methylprednisolone] rapidly declined to near basal
      concentrations at 4 h and 2 h, respectively, post-administration. Therefore the
      order of stability in CSF and blood was MnTBAP >> EUK-134 > methylprednisolone.
      The maximum CSF/blood concentration ratios for EUK-134, methylprednisolone and
      MnTBAP post-administration were: 32 +/- 3.1%, 19.2 +/- 6.4%, and 4.42 +/- 0.73%
      in the injured rats, and 22 +/- 6.5%, 17.8 +/- 2.9%, and 1.0 +/- 0.5% in the sham
      control animals. This suggests an order of BSB penetration of EUK-134 >
      methylprednisolone >> MnTBAP. Despite much lower penetration by MnTBAP compared
      with EUK-134 and methylprednisolone, a lower dose of MnTBAP because of its
      stability provided a higher concentration in CSF than did the other agents given
      at higher doses. This finding supports further exploration of MnTBAP as a
      potential treatment for SCI.

PMID- 22640222
TI  - Early detection of left ventricular systolic dysfunction using two-dimensional
      speckle tracking strain evaluation in healthy subjects after acute alcohol
      intoxication.
AB  - OBJECTIVES: We evaluated the ability of two-dimensional speckle tracking strain
      echocardiography to detect left ventricular (LV) systolic dysfunction as compared
      with LV ejection fraction (EF) in healthy subjects following acute alcohol
      intoxication. METHODS AND RESULTS: In total, 25 healthy subjects were
      investigated using echocardiography 4-6 hours after the onset of alcohol
      intoxication at a regional festive gathering, and then compared to 23 healthy
      control subjects without alcohol consumption. Heart rate, blood pressure, blood
      alcohol level, LV volumes, EF, shortening fraction, E/A ratio, as well as global
      longitudinal strain (LS) were recorded. Mean blood alcohol level was 1.3 +/- 0.3
      g.L(-1) . Mean systolic blood pressure and heart rate were slightly increased in
      the alcohol group compared to controls (147.5 +/- 21.8 mmHg vs 127.0 +/- 9.9
      mmHg, P = 0.003, and 79.7 +/- 10.7 bpm vs 70.6 +/- 7.6 bpm, P < 0.001,
      respectively). While there was no significant difference in terms of LVEF (62.9
      +/- 4.4% vs 64.8 +/- 5.9%, P = 0.18) or shortening fraction (34.7 +/- 5.9% vs
      36.0 +/- 4.3%, P = 0.54), global LS was significantly impaired (-17.8 +/- 2.0% vs
      -21.2 +/- 1.8%, P < 0.001). In addition, subjects who consumed alcohol had
      increased LV end-diastolic (108.3 +/- 20.1 mL vs 95.5 +/- 14.6 mL, P = 0.037) and
      end-systolic volumes (41.6 +/- 11.4 mL vs 33.7 +/- 6.9 mL, P = 0.024), along with
      depressed aortic time-velocity integral (19.9 +/- 3.2 mL vs 21.9 +/- 2.5 mL, P =
      0.034). According to multivariate linear regression analyses, blood alcohol level
      was the only factor significantly associated with global LS (beta=-3.6 +/- 1.0, P
      = 0.005). CONCLUSION: Alcohol intoxication around festive days induces acute LV
      contraction abnormalities, which may be detected using global LS by speckle
      tracking at an earlier stage and more accurately than LVEF decreases.

PMID- 22640223
TI  - Problem perception, technology and effectiveness in medical practice.
AB  - RATIONALE, AIMS AND OBJECTIVES: Evidence-based medicine and clinical guidelines
      have been found difficult to implement in the clinical practice--mainly because
      lack of evidence quality and guidelines that, generally, do not account for
      variations in the medical cases. Variation in the medical cases enhances task
      uncertainty and uncertainty seems to be further enhanced through clinical
      guidelines. In this article, concept development is attempted, where task
      uncertainty is classified into a few medical problem-solving processes according
      to differences in medical technology and in the (initial) perception of the
      medical problem. Furthermore is argued the need for using different strategies in
      evaluating performance quality in medical health care depending on the variation
      in the degree of task uncertainty. METHOD: Qualitative data about medical
      activities related to certain diseases are used to exemplify problem-solving
      processes representing different types of task uncertainty. RESULTS: It is argued
      that the main characteristics of medical problem-solving processes vary according
      to differences in medical technology and perception of perceived medical problem.
      Four main medical problem-solving processes are defined and demonstrated through
      empirical examples. CONCLUSION: What may be regarded as rational behaviour is
      different for each type of problem-solving processes. Consequently, the processes
      need different organizational settings and need to be evaluated according to
      different criteria. Furthermore, from a practical point of view, development and
      education related to problem perception would seem as important as development of
      medical technology.

PMID- 22640225
TI  - Maxim D. Frank-Kamenetskii: Diamond Jubilee of A Brilliant Scientist.
AB  - Abstract   Long-time friend, colleague and disciple of Maxim D. Frank-Kameneskii,
      Dr. Vadim V. Demidov, writes on Maxim on Maxim's 60th birthday. JBSD and Adenine
      Press join these congratulations and wish the jubilarian a happy birthday and
      many-many happy returns!

PMID- 22640226
TI  - Characterization, antibiofilm, and mechanism of action of novel PEG-stabilized
      lipid nanoparticles loaded with terpinen-4-ol.
AB  - Terpinen-4-ol, an active component of tea tree oil, exhibits broad-spectrum
      antimicrobial activity. However, the high volatilization of terpinen-4-ol and its
      nonwettability property have limited its application. Our objective was to
      synthesize novel nanocarriers to deliver and protect terpinen-4-ol. The
      polyethylene glycol (PEG)-stabilized lipid nanoparticles were prepared and
      characterized by scanning electron microscope, Zetasizer, and differential
      scanning calorimetry. These nanoparticles had an average diameter of 397 nm and a
      Zeta-potential of 10 mV after being modified by glycine. Results showed that
      homogeneous particle size, high drug loading, stability, and targeting were
      obtained by the nanoparticles. Liquid chromatography/mass spectrometry showed a
      sustained release trend from nanoparticles for terpinen-4-ol. Minimum inhibitory
      concentration and minimum biofilm eradication concentration were tested against
      Candida albicans ATCC 11231. Studies on isolated mitochondria showed the blockage
      of biofilm respiration and inhibition of enzyme activity. The effects can be
      ascribed to localization of terpinen-4-ol on the membrane of mitochondria.

PMID- 22640227
TI  - Atypical FTLD-FUS associated with ALS-TDP: a case report.
AB  - A 30-year-old Japanese woman without relevant family history presented with a
      behavioral abnormality followed by motor weakness about 14 years later. The
      patient died at age 45. Post mortem examination revealed degeneration of the
      frontal and temporal lobes, as well as lower motor neurons in the brainstem and
      spinal cord. These features were reported previously as being consistent with a
      diagnosis of frontotemporal lobar degeneration (FTLD) with amyotrophic lateral
      sclerosis (ALS). In the present study, we show abundant fused in sarcoma (FUS)
      positive dystrophic neurites but only a few neuronal cytoplasmic inclusions in
      the frontal and temporal cortices. TAR DNA-binding protein 43 (TDP-43)-positive
      inclusions were absent in the cerebrum. However, TDP-43-positive inclusions were
      present in the lower motor neurons of the brainstem and spinal cord. To our
      knowledge, this is the first report of a case in which FTLD-FUS pathology is of a
      dystrophic neurites-predominant type and FTLD-FUS is associated with ALS-TDP.

PMID- 22640228
TI  - A primer for achieving glycemic control in the cardiac surgical patient.
AB  - Maintaining glycemic control (blood glucose <180 mg/dL) has been shown to reduce
      morbidity and enhance long-term survival in patients with diabetes mellitus
      following coronary artery bypass graft (CABG) surgery. In this review we present
      a management strategy to achieve perioperative glycemic control in all patients
      undergoing CABG surgery, with and without diabetes mellitus, designed to achieve
      compliance with current Surgical Care Improvement Project (SCIP) and Society of
      Thoracic Surgeons (STS) guidelines.

PMID- 22640224
TI  - Allergen-specific immunotherapy: from therapeutic vaccines to prophylactic
      approaches.
AB  - Immunoglobulin E-mediated allergies affect more than 25% of the population.
      Allergen exposure induces a variety of symptoms in allergic patients, which
      include rhinitis, conjunctivitis, asthma, dermatitis, food allergy and life
      threatening systemic anaphylaxis. At present, allergen-specific immunotherapy
      (SIT), which is based on the administration of the disease-causing allergens, is
      the only disease-modifying treatment for allergy. Current therapeutic allergy
      vaccines are still prepared from relatively poorly defined allergen extracts.
      However, with the availability of the structures of the most common allergen
      molecules, it has become possible to produce well-defined recombinant and
      synthetic allergy vaccines that allow specific targeting of the mechanisms of
      allergic disease. Here we provide a summary of the development and mechanisms of
      SIT, and then review new forms of therapeutic vaccines that are based on
      recombinant and synthetic molecules. Finally, we discuss possible allergen
      specific strategies for prevention of allergic disease.

PMID- 22640229
TI  - Comparative study of the outcome of induction of labor using 25 ug and 50 ug of
      vaginal misoprostol.
AB  - OBJECTIVE: To compare the safety and effectiveness of vaginal misoprostol 25 MUg
      with those of 50 MUg in induction of labor. METHOD: One hundred and sixty
      eligible women of low parity with indications for induction of labor at term were
      enrolled for the study. The subjects were randomized into two groups of vaginal
      misoprostol 25 ug and 50 ug dose regimens. Maternal characteristics, labor and
      newborn outcome were compared. RESULTS: The total duration of labor was
      significantly shorter in the 50 ug group (8.24 +/- 1.5 h) than 25 ug group (9.09
      +/- 2.7 h), p = 0.02. Oxytocin augmentation was significantly higher in the 25 ug
      group (18.75%) than in the 50 ug group (7.5%), p = 0.04. The indications for
      caesarean section were significantly different, (p = 0.02) between the two groups
      although the incidence was similar. The intrapartum adverse effects like fetal
      distress, meconium stained liquor, and tachysystole were significantly higher in
      the 50 ug group, p = 0.003. Similarly, the postpartum adverse effects such as
      cervical and vaginal tears were significantly higher in 50 ug group, p = 0.01.
      CONCLUSION: The two dose regimens were both effective in induction of labor, but
      50 ug dose regimen resulted in significantly shorter duration of labor but with
      higher rate of labor complications than the 25 ug dose regimen.

PMID- 22640231
TI  - Low-grade chronic inflammation and superoxide anion production by NADPH oxidase
      are the main determinants of physical frailty in older adults.
AB  - BACKGROUND: Physical performance measured by gait speed is being recognized as a
      major instrument for clinical evaluation in older adults, because it predicts
      physical frailty, loss of autonomy, hospitalization and decreased survival. Low
      grade chronic inflammation and oxidative stress, mediated partly by the
      superoxide anion produced by NADPH oxidase, are closely linked and could be
      involved in age-related physical decline. OBJECTIVE: To determine whether slow
      gait speed is associated with superoxide anion overproduction by NADPH oxidase
      and low-grade chronic inflammation. DESIGN AND SETTING: Observational study among
      the 280 elderly of an ambulatory geriatric care unit (191 women, 89 men, 79.9 +/-
      6.1 years old). METHODS: Gait speed was evaluated by walking at self-chosen usual
      pace. Usual gait speed < 0.8 m/s was defined as slow gait speed. Superoxide anion
      production was evaluated using a lucigenin-based chemiluminescence method.
      Inflammation was evaluated by CRP, fibrinogen and leukocyte count. RESULTS: Among
      the 280 participants, 179 (63.9%) walked with a gait speed < 0.8 m/s (slow
      walkers) and 101 (36.1%) with a gait speed >= 0.8 m/s. Superoxide production and
      inflammation markers, such as fibrinogen, were more important in slow walkers (p
      = 0.004 and p = 0.006, respectively). In multivariate analysis, superoxide anion
      overproduction and fibrinogen were independently associated with physical frailty
      assessed by slow gait speed (p = 0.028 and p = 0.007, respectively). CONCLUSION:
      Physical frailty in older people is associated with superoxide anion
      overproduction by NADPH oxidase and low-grade chronic inflammation.

PMID- 22640230
TI  - Expression of hormone receptors, cell regulatory and myoepithelial cell markers
      in lactating breast and associated carcinomas.

PMID- 22640233
TI  - From study day to centre for the study of control measures: an example of
      codevelopment.

PMID- 22640232
TI  - Clinical correlates of sex steroids and gonadotropins in men over the late
      adulthood: the Framingham Heart Study.
AB  - Low serum concentrations of sex steroids and gonadotropins in men have been
      associated with increased cardiometabolic risk and mortality, but the clinical
      correlates of these hormones in men over late adulthood are less clearly
      understood. We analysed up to five serial measurements of total testosterone
      (TT), dehydroepiandrosterone sulphate (DHEAS), follicle stimulating hormone
      (FSH), luteinizing hormone (LH) and total estradiol (EST) in older men in the
      original cohort of the Framingham Heart Study to determine the short- (2-years;
      1,165 person-observations in 528 individuals) and long-term (up to 10-years
      follow-up; 2520 person-observations in 835 individuals with mean baseline age:
      71.2 years) clinical correlates of these sex steroids and gonadotropins using
      multilevel modelling and Generalized Estimating Equations. Age, body mass index
      and pre-existing type 2 diabetes were inversely related to long-term TT
      concentrations, whereas higher systolic blood pressure showed a positive
      association. Furthermore, age and pre-existing cardiovascular disease (CVD) were
      inversely associated and HDL cholesterol concentrations positively associated
      with long-term DHEAS concentrations respectively. Analyses of short-term changes
      revealed age was inversely related to DHEAS, but positively related to FSH and LH
      concentrations. Our community-based study identified modifiable correlates of
      decreasing TT and DHEAS concentrations in elderly men, suggesting that
      maintenance of a low CVD risk factor burden may mitigate the age-related decline
      of these hormones over the late adulthood.

PMID- 22640235
TI  - Expression of Alt a 1 allergen from Alternaria alternata in the yeast Yarrowia
      lipolytica.
AB  - Allergies affect almost 25% of the population in industrialized countries.
      Alternaria alternata is known to be a significant source of aeroallergens and
      sensitization to this mold is a risk factor for the development of wheezing,
      asthma, and atopic dermatitis. Diagnosis and treatment of allergies requires the
      production of large amounts of pure and well defined protein. Yarrowia
      lipolytica, a non-pathogenic ascomycete able to secrete high levels of enzymes
      that can grow in inexpensive substrates, has been considered a useful host for
      heterologous gene expression. In the present work, we have developed two vectors
      for expressing Alt a 1, the most relevant A. alternata allergen, in Y.
      lipolytica. One vector is autosomal and one is integrative. With both systems,
      rAlt a 1 was secreted into the culture medium. The immunological characteristics
      of the purified recombinant allergen were determined by IgE-blot using sera from
      42 A. alternata-allergic patients. We have carried out ELISA-inhibition
      experiments using sera from four patients to compare the IgE-binding capacity of
      natural and recombinant allergens. Our results show that Y. lipolytica is able to
      produce a recombinant Alt a 1 which is immunochemically equivalent to the natural
      counterpart and could be used for immunotherapy and diagnostics.

PMID- 22640234
TI  - How patients understand depression associated with chronic physical disease--a
      systematic review.
AB  - BACKGROUND: Clinicians are encouraged to screen people with chronic physical
      illness for depression. Screening alone may not improve outcomes, especially if
      the process is incompatible with patient beliefs. The aim of this research is to
      understand people's beliefs about depression, particularly in the presence of
      chronic physical disease. METHODS: A mixed method systematic review involving a
      thematic analysis of qualitative studies and quantitative studies of beliefs held
      by people with current depressive symptoms. MEDLINE, EMBASE, PSYCHINFO, CINAHL,
      BIOSIS, Web of Science, The Cochrane Library, UKCRN portfolio, National Research
      Register Archive, Clinicaltrials.gov and OpenSIGLE were searched from database
      inception to 31st December 2010. A narrative synthesis of qualitative and
      quantitative data, based initially upon illness representations and extended to
      include other themes not compatible with that framework. RESULTS: A range of
      clinically relevant beliefs was identified from 65 studies including the
      difficulty in labeling depression, complex causal factors instead of the
      biological model, the roles of different treatments and negative views about the
      consequences of depression. We found other important themes less related to ideas
      about illness: the existence of a self-sustaining 'depression spiral'; depression
      as an existential state; the ambiguous status of suicidal thinking; and the role
      of stigma and blame in depression. CONCLUSIONS: Approaches to detection of
      depression in physical illness need to be receptive to the range of beliefs held
      by patients. Patient beliefs have implications for engagement with depression
      screening.

PMID- 22640236
TI  - Lymphedematous verrucous changes simulating squamous cell carcinoma in long
      standing hidradenitis suppurativa.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a relatively common condition marked
      by abscesses, sinus tracts, and scarring in intertriginous regions of the body.
      Lymphedema is an under-recognized consequence of chronic inflammation in the
      setting HS. METHODS: We report five cases of patients with lymphedema resulting
      from long-standing HS; the patients were seen either in a specialty HS clinic or
      general dermatology clinic at our institution. Biopsies for histologic analysis
      were performed on four of the five patients reported here. RESULTS: Changes of
      lymphedema may be manifested diffusely as widespread plaques or focally as
      verrucous papules and nodules. The latter may be difficult to distinguish
      clinically from squamous cell carcinoma, another complication of chronic HS.
      Histopathologic features of lymphedema include dilated lymphatic channels,
      diffuse edema, verrucous epidermal hyperplasia, mixed inflammation, and dermal
      fibrosis. CONCLUSION: Lymphedema associated with chronic HS, which we also term
      "verrucous lymphostasis," encompasses a spectrum of clinical and histopathologic
      findings. Squamous cell carcinoma may mimic focal presentations of lymphedema,
      and biopsy may be necessary to distinguish the two.

PMID- 22640238
TI  - Characteristics of type I Gaucher disease associated with persistent
      thrombocytopenia after treatment with imiglucerase for 4-5 years.
AB  - The characteristics of Gaucher disease (GD) associated with persistent
      thrombocytopenia despite imiglucerase enzyme therapy in type 1 GD (GD1) were
      investigated by retrospective analysis of International Collaborative Gaucher
      Group (ICGG) Registry data. The study involved 1016 GD1 patients with an intact
      spleen for whom date of diagnosis, therapy initiation, and platelet counts were
      known, and who received continuous imiglucerase therapy for 4 to 5 years. These
      patients were stratified by last platelet count: >= 120 * 10(9) /l (n = 772); >=
      100 to <120 * 10(9) /l (n = 94); >= 80 to <100 * 10(9) /l (n = 80); and <80 *
      10(9) /l (n = 70; 20 with <60 * 10(9) /l) and characterized by initial and
      cumulative average imiglucerase dose, body mass index, platelet count, anaemia,
      hepatomegaly, splenomegaly, and skeletal assessments at baseline and after 4-5
      years of therapy. Statistically significant associations were found between
      persistent thrombocytopenia and baseline platelet count (<80 * 10(9) /l),
      splenomegaly, and anaemia (all P < 0.0001). After 4-5 years, statistically
      significant associations were found with splenomegaly (P < 0.0001), anaemia (P <
      0.0001), white blood cell count (P = 0.049), hepatomegaly (P = 0.004) and bone
      pain (P = 0.035). Exponential platelet decay in relation to splenomegaly suggests
      that platelets increase only when spleen volume decreases substantially.

PMID- 22640239
TI  - Cognitive function with glucose tolerance status and obesity in Chinese middle
      aged and aged adults.
AB  - OBJECTIVES: To evaluate the relationship of cognitive function with glucose
      tolerance status and obesity in Chinese middle-aged or aged adults. METHODS: A
      sample of 1722 subjects aged 40 years or order was investigated from four
      communities in Shijingshan District, Beijing, China. People with any emotional
      disorder, substance abuse, known diabetes or stroke were excluded. Global
      cognitive function was measured by the Mini-Mental State Examination (MMSE).
      RESULTS: People with normal glucose tolerance showed higher mean MMSE scores
      compared to those with pre-diabetes or diabetes (p > 0.05 in males, p < 0.05 in
      females). People with ideal BMI (18.5-23.9) showed higher mean MMSE scores
      compared to those with BMI < 18.5 or BMI >= 24, but there was no statistical
      significance (p < 0.05) The significantly lower MMSE scores was shown in the
      groups with waist circumferences >= 85 cm in males, or >= 80 cm in females (p <
      0.05). The multivariate linear regression analysis showed significant association
      of MMSE with waist circumferences, SBP, HDL-c and FPG (p=0.000, B=-0.179;
      p=0.000, B =-0.073; p=0.016, B=0.165; p=0.028, B=-0.124, respectively), except
      the association with age, education, economic income, smoking and alcohol intake.
      CONCLUSIONS: In middle aged or aged residents, glucose tolerance status, obesity,
      and especially central obesity may be the important contributors to cognitive
      impairment.

PMID- 22640237
TI  - Science and medicine applied to soccer refereeing: an update.
AB  - Soccer referees are required to keep up with play at all times to ensure optimal
      positioning in making key decisions. While the physiological aspects of soccer
      refereeing have been extensively reviewed, other key areas of preparation and
      performance have yet to be considered in detail. We present a contemporary
      examination of methodological considerations for the interpretation of referees'
      match activities, the validation of fitness testing and training protocols, match
      and training injury profiles, and the understanding and development of perceptual
      cognitive expertise. A referee covers approximately 11 km during a match, with
      ~900 m of high-speed running and, consequently, the demands of match play
      represent a significant physical challenge. The analyses of within-match activity
      profiles have attempted to assess the possible occurrence of referee fatigue,
      with equivocal findings. However, researchers have demonstrated that referees'
      physical performances are interrelated with those of the players during the same
      match. Therefore, the evaluation of referees' match activity profiles should be
      made in the context of the players' performances. High match-to-match variability
      in key variables, namely, high-speed running and sprinting, along with age
      related reductions in match running are other factors that require due
      consideration when interpreting physical performances. Fitness testing is used by
      national and international referee governing bodies as part of their match
      selection criteria. Therefore, the tests need to reflect the physical task of
      refereeing, yet for the recent fitness tests introduced by the Federation
      Internationale de Football Association--a 20 * 150 m high-intensity and 6 * 40 m
      repeated-sprint test - only the repeated-sprint test possesses the appropriate
      construct validity for assessment of match-related running capacity. Also, the
      performance standards of the tests have not been validated. Consequently, the
      scientific rationale behind the tests and their associated standards is not
      clear. Soccer referees dedicate a large proportion of their overall training to
      the development of physical capacity and researchers have demonstrated that high
      intensity (>85% maximal heart rate) training protocols are effective for
      improving fitness and match running performance. These high training loads
      combined with increasing age could, in part, explain an incidence of non-contact
      match injuries (18 injuries per 1000 match hours) similar to players, with lower
      leg muscle strains being the most common type of non-contact injuries in
      referees. The implementation of injury prevention programmes along with the
      careful monitoring of training and match loads may help minimize referee's injury
      incidence. The perceptual-cognitive demands of soccer refereeing are significant,
      yet there remains limited research examining the perceptual and cognitive
      processes informing referees' decisions. As such, a three-step approach for the
      study of expertise in soccer referees is proposed. First, objective and reliable
      markers of decision making should be established, with due consideration to the
      development of naturalistic test situations while maintaining experimental
      control. Second, process-tracing measures can be used to identify the perceptual
      and cognitive mechanisms involved in accurate decision making. Finally, research
      is required to help understand the acquisition of superior decision making and
      whether such expertise can be developed via training programmes.

PMID- 22640240
TI  - The "Truman Show" delusion: psychosis in the global village.
AB  - INTRODUCTION: We report a novel delusion, primarily persecutory in form, in which
      the patient believes that he is being filmed, and that the films are being
      broadcast for the entertainment of others. METHODS: We describe a series of
      patients who presented with a delusional system according to which they were the
      subjects of something akin to a reality television show that was broadcasting
      their daily life for the entertainment of others. We then address three
      questions, the first concerning how to characterise the delusion, the second
      concerning the role of culture in delusion, and the third concerning the
      implications of cultural studies of delusion for the cognitive theory of
      delusion. RESULTS: Delusions are both variable and stable: Particular delusional
      ideas are sensitive to culture, but the broad categories of delusion are stable
      both across time and culture. This stability has implications for the form a
      cognitive theory of delusion can take. CONCLUSIONS: Cultural studies of delusion
      have important contributions to make to the cognitive theory of delusion.

PMID- 22640257
TI  - Interplay of RsbM and RsbK controls the sigma(B) activity of Bacillus cereus.
AB  - The alternative transcription factor sigma(B) of Bacillus cereus controls the
      expression of a number of genes that respond to environmental stress. Four
      proteins encoded in the sigB gene cluster, including RsbV, RsbW, RsbY (RsbU) and
      RsbK, are known to be essential in the sigma(B)-mediated stress response. In the
      context of stress, the hybrid sensor kinase RsbK is thought to phosphorylate the
      response regulator RsbY, a PP2C serine phosphatase, leading to the
      dephosphorylation of the phosphorylated RsbV. The unphosphorylated RsbV then
      sequesters the sigma(B) antagonist, RsbW, ultimately liberating sigma(B). The
      gene arrangement reveals an open reading frame, bc1007, flanked immediately
      downstream by rsbK within the sigB gene cluster. However, little is known about
      the function of bc1007. In this study, the deletion of bc1007 resulted in high
      constitutive sigma(B) expression independent of environmental stimuli, indicating
      that bc1007 plays a role in sigma(B) regulation. A bacterial two-hybrid analysis
      demonstrated that BC1007 interacts directly with RsbK, and autoradiographic
      studies revealed a specific C(14)-methyl transfer from the radiolabelled S
      adenosylmethionine to RsbK when RsbK was incubated with purified BC1007. Our data
      suggest that BC1007 (RsbM) negatively regulates sigma(B) activity by methylating
      RsbK. Additionally, mutagenic substitution was employed to modify 12 predicted
      methylation residues in RsbK. Certain RsbK mutants were able to rescue sigma(B)
      activation in a rsbK-deleted bacterial strain, but RsbK(E439A) failed to activate
      sigma(B), and RsbK(E446A) only moderately induced sigma(B). These results suggest
      that Glu439 is the preferred methylation site and that Glu446 is potentially a
      minor methylation site. Gene arrays of the rsbK orthologues and the neighbouring
      rsbM orthologues are found in a wide range of bacteria. The regulation of sigma
      factors through metylation of RsbK-like sensor kinases appears to be widespread
      in the microbial world.

PMID- 22640258
TI  - Exploring sources of knowledge utilized in practice among Jordanian registered
      nurses.
AB  - RATIONALE, AIMS AND OBJECTIVES: Understanding sources of knowledge used in
      everyday practice is very helpful in improving the quality of health care
      services. There is a consensus in the literature that nurses mostly relied in
      their practice on experiential knowledge gained through their interactions with
      other members of health care professionals and patients. The general aim of this
      study is to explore the sources of knowledge Jordanian registered nurses use
      during their practice. METHOD: A descriptive correlational design was used to
      collect data from 539 Jordanian registered nurses from 10 hospitals using a self
      administered questionnaire. RESULTS: The mean year of experience of the sample
      was 7.08 years. Of the 615 questionnaires distributed, 555 were returned. This
      yields a response rate of 87.6%. Results revealed that the top five ranked
      sources used by Jordanian registered nurses include: the information that nurses
      learned during nursing education, personal experience in nursing over time, what
      was learned through providing care to patients, information gained through
      discussion between physicians and nurses about patients, and information from
      policy and procedure manuals. CONCLUSION: Jordanian registered nurses recognize
      the value of research and that research utilization (RU) is an important issue
      and must not be ignored. The study has many implications for practice, education
      and research. Health care managers and decision makers need to play a more
      visible and instrumental role in encouraging RU to improve patients' quality of
      life.

PMID- 22640259
TI  - Analysis of mitochondrial DNA in Bolivian llama, alpaca and vicuna populations: a
      contribution to the phylogeny of the South American camelids.
AB  - The objectives of this work were to assess the mtDNA diversity of Bolivian South
      American camelid (SAC) populations and to shed light on the evolutionary
      relationships between the Bolivian camelids and other populations of SACs. We
      have analysed two different mtDNA regions: the complete coding region of the MT
      CYB gene and 513 bp of the D-loop region. The populations sampled included
      Bolivian llamas, alpacas and vicunas, and Chilean guanacos. High levels of
      genetic diversity were observed in the studied populations. In general, MT-CYB
      was more variable than D-loop. On a species level, the vicunas showed the lowest
      genetic variability, followed by the guanacos, alpacas and llamas. Phylogenetic
      analyses performed by including additional available mtDNA sequences from the
      studied species confirmed the existence of the two monophyletic clades previously
      described by other authors for guanacos (G) and vicunas (V). Significant levels
      of mtDNA hybridization were found in the domestic species. Our sequence analyses
      revealed significant sequence divergence within clade G, and some of the Bolivian
      llamas grouped with the majority of the southern guanacos. This finding supports
      the existence of more than the one llama domestication centre in South America
      previously suggested on the basis of archaeozoological evidence. Additionally,
      analysis of D-loop sequences revealed two new matrilineal lineages that are
      distinct from the previously reported G and V clades. The results presented here
      represent the first report on the population structure and genetic variability of
      Bolivian camelids and may help to elucidate the complex and dynamic domestication
      process of SAC populations.

PMID- 22640260
TI  - Using GRADE methodology for the development of public health guidelines for the
      prevention and treatment of HIV and other STIs among men who have sex with men
      and transgender people.
AB  - BACKGROUND: The World Health Organization (WHO) Department of HIV/AIDS led the
      development of public health guidelines for delivering an evidence-based,
      essential package of interventions for the prevention and treatment of HIV and
      other sexually transmitted infections (STIs) among men who have sex with men
      (MSM) and transgender people in the health sector in low- and middle-income
      countries. The objective of this paper is to review the methodological challenges
      faced and solutions applied during the development of the guidelines. METHODS:
      The development of the guidelines followed the WHO guideline development process,
      which utilizes the GRADE approach. We identified, categorized and labeled the
      challenges identified in the guidelines development process and described the
      solutions through an interactive process of in-person and electronic
      communication. RESULTS: We describe how we dealt with the following challenges:
      (1) heterogeneous and complex interventions; (2) paucity of trial data; (3)
      selecting outcomes of interest; (4) using indirect evidence; (5) integrating
      values and preferences; (6) considering resource use; (7) addressing social and
      legal barriers; (8) wording of recommendations; and (9) developing global
      guidelines. CONCLUSION: We were able to successfully apply the GRADE approach for
      developing recommendations for public health interventions. Applying the general
      principles of the approach while carefully considering specific challenges can
      enhance both the process and the outcome of guideline development.

PMID- 22640261
TI  - Methylseleninic acid restricts tumor growth in nude mice model of metastatic
      breast cancer probably via inhibiting angiopoietin-2.
AB  - BACKGROUND: Angiopoietin-2 (Ang-2) plays critical roles in vascular morphogenesis
      and its upregulation is frequently associated with various tumors. Previous
      studies showed that certain selenium compounds possess anti-tumor effects.
      However, the underlining mechanism has not been elucidated in detail. Plus,
      results of research on the anti-tumor effects of selenium compounds remain
      controversial. METHODS: We investigated levels of Ang-2 and vascular endothelial
      growth factor (VEGF) on the estrogen-independent bone metastatic mammary cancer
      (MDA-MB-231) cells in response to treatment by methylseleninic acid (MSeA), and
      further examined the effects of MSeA oral administration on xenograft mammary
      tumors of athymic nude mice by RT-PCR, Western, radioimmuno assay, and
      Immunohistochemistry. RESULTS: Treatment of MDA-MB-231 cells with MSeA caused
      significant reduction of Ang-2 mRNA transcripts and secretion of Ang-2 proteins
      by the cells. Level of VEGF protein was accordingly decreased following the
      treatment. Compared with the controls, oral administration of MSeA (3 mg/kg/day
      for 18 days) to the nude mice carrying MDA-MB-231 induced tumors resulted in
      significant reduction in xenograft tumor volume and weights, significant decrease
      in microvascular density, and promotion of vascular normalization by increasing
      pericytes coverage. As expected, level of VEGF was also decreased in MSeA treated
      tumors. CONCLUSIONS: Our results point out that MSeA exerts its anti-tumor
      effects, at least in part, by inhibiting the Ang-2/Tie2 pathway, probably via
      inhibiting VEGF.

PMID- 22640262
TI  - High calcium enhances calcium oxalate crystal binding capacity of renal tubular
      cells via increased surface annexin A1 but impairs their proliferation and
      healing.
AB  - Hypercalciuria is associated with kidney stone formation and impaired renal
      function. However, responses of renal tubular cells upon exposure to high-calcium
      environment remain largely unknown. We thus performed a proteomic analysis of
      altered proteins in renal tubular cells induced by high-calcium and evaluated
      functional significance of these changes. MDCK cells were maintained with or
      without 20 mM CaCl(2) for 72 h. Cellular proteins were then analyzed by two
      dimensional electrophoresis (2-DE) (n = 5 gels derived from 5 independent culture
      flasks per group). Spot matching and quantitative intensity analysis revealed 20
      protein spots (from a total of 700) that were differentially expressed between
      the two groups. These altered proteins were then identified by Q-TOF-MS and MS/MS
      analyses, including those involved in calcium binding, protein synthesis,
      carbohydrate metabolism, lipid metabolism, cell proliferation, mitosis
      regulation, apoptosis, cell migration, oxidative stress, and ion transport.
      Protein network analysis and functional validation revealed that high-calcium
      exposed cells had 36.5% increase in calcium oxalate monohydrate (COM) crystal
      binding capacity. This functional change was consistent to the expression data in
      which annexin A1 (ANXA1), a membrane-associated calcium-binding protein, was
      markedly increased on the apical surface of high-calcium-exposed cells.
      Pretreatment with anti-ANXA1 antibody could neutralize this increasing crystal
      binding capacity. Moreover, high-calcium exposure caused defects in cell
      proliferation and wound healing. These expression and functional data demonstrate
      the enhanced crystal-binding capacity but impaired cell proliferation and wound
      healing in renal tubular cells induced by high-calcium. Taken together, these
      phenomena may contribute, at least in part, to the pathogenic mechanisms of
      hypercalciuria-induced nephrolithiasis and impaired renal function. Our in vitro
      study offers several candidates for further targeted functional studies to
      confirm their relevance in hypercalciuria and kidney stone disease in vivo.

PMID- 22640263
TI  - Transapical approach for apical myectomy and relief of midventricular obstruction
      in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Apical and midventricular hypertrophic cardiomyopathy (HCM) are rare
      variants of HCM, in which the hypertrophy is located mainly at the midventricular
      to apical levels. Heart transplantation was the only possible surgical solution
      for many of these patients; however, transapical myectomy represents another good
      alternative. We present our surgical technique of apical ventriculotomy for
      apical and midventricular myectomy. TECHNIQUE: A 6-cm incision is made at the
      apex of the heart lateral to the left anterior descending coronary artery. The
      apical ventriculotomy provides excellent exposure of the midventricle for
      midventricular myectomy. The apical approach also allows access to the left
      ventricle for apical myectomy to enlarge the chamber. During apical myectomy,
      particular care is necessary to avoid injury to papillary muscles, which are
      often displaced with apical HCM. Secure closure of the ventriculotomy can be
      achieved with a double layer of suture reinforced with felt, and no complications
      of false aneurysm have been observed. CONCLUSIONS: The transapical approach
      provides excellent exposure of the apex and midventricle, and the technique is
      useful when myectomy is aimed at eliminating the ventricular obstruction and/or
      enlarging the left ventricular cavity size in patients with apical hypertrophy.

PMID- 22640264
TI  - Chronic rhinosinusitis and asthma: novel understanding of the role of IgE 'above
      atopy'.
AB  - Chronic rhinosinusitis (CRS) affects more than 10% of the European population and
      is often associated with asthma. Phenotypes of CRS can be differentiated based on
      mucosal remodelling and inflammatory patterns. Understanding the role of central
      mediators, such as interleukin-5, in these different phenotypes may lead to the
      development of specific therapeutic approaches. The impact of staphylococcal
      superantigens has been shown to further modify the immune response, contributing
      to persistent severe disease via the activation of T and B cells and the
      formation of local IgE. It is clear that these mechanisms are involved in the
      systemic spread of upper airway disease with resulting asthma comorbidity, when
      IgE antibodies to staphylococcal enterotoxins are present at measurable levels in
      serum. Recent findings point to superantigens as possible causal agents in the
      intrinsic form of severe asthma, and an anti-IgE strategy has shown promising
      therapeutic potential in nonatopic patients with nasal polyps and asthma. These
      findings should lead to a clinically relevant endotyping of patients with upper
      and lower airway disease and to a new understanding of the role of IgE 'above
      atopy'.

PMID- 22640265
TI  - Corpus luteum hemorrhage in a patient with aplastic anemia.
AB  - Corpus luteum hemorrhage may lead to a life-threatening intraperitoneal
      hemorrhage in women with bleeding disorders. A 17-year-old girl with aplastic
      anemia presented to the emergency ward with complaints of severe abdominal pain
      for the last 24h. On examination, she was noted to be pale with circulatory
      compromise. Transabdominal pelvic ultrasonography revealed a left complex adnexal
      mass, 6.9*5.1*5.1cm(3) in size, with a large anechoic area of fluid in the
      abdomen. On laparoscopic exploration, there was a massive hemoperitoneum (2.6L)
      with a ruptured corpus luteum on the surface of the left ovary. Hemostatic
      electric coagulation was successfully applied to the bleeding surface. The
      patient recovered without incident and was transferred to a special hospital for
      blood disease treatment one week after surgery. We concluded that corpus luteum
      hemorrhage in women with aplastic anemia can cause therapeutic difficulties.
      Laparoscopy is feasible for the management of a massive intraperitoneal
      hemorrhage secondary to a ruptured corpus luteum in such patients.

PMID- 22640266
TI  - Mesenchymal stem cells are a rescue approach for recovery of deteriorating kidney
      function.
AB  - AIM: Stem cell (SC) therapy for chronic kidney disease (CKD) is urgently needed.
      The use of mesenchymal stem cells (MSC) is a possible new therapeutic modality.
      Our work aimed to isolate human MSC from adult bone marrow to improve kidney
      functions in CKD patients. METHODS: In our study 30 patients with impaired kidney
      function were included, their ages ranged from 22 to 68 years. They included 10
      inactive glomerulonephritis patients due to systemic lupus erythromatosus (SLE)
      (group I), 10 renal transplantation cases (group II) and 10 patients of other
      aetiologies as the control group. Fifty millilitres of bone marrow was aspirated
      from the iliac bone, for separation of MSC. RESULTS: There was a highly
      statistically significant difference between both CD271 and CD29 before and after
      culture with increase of both markers at end of culture, P < 0.01. Finally 50-70
      million MSC in 10 mL saline (0.7-1.0 * 10(6) MSC/kg body weight) were infused
      intravenously in two divided doses one week apart. There was a highly
      statistically significant difference between each of serum creatinine and
      creatinine clearance levels before and after MSC injection at 1, 3 and 6 months
      post-infusion with SLE cases showing a greater decline of their serum creatinine
      and elevation of mean creatinine clearance levels after injection than
      transplantation and control groups, P < 0.05. CONCLUSION: Mesenchymal stem cells
      therapy is a potential therapeutic modality for early phases of CKD.

PMID- 22640267
TI  - Quality of life among caregivers of patients with schizophrenia: a cross-cultural
      comparison of Chilean and French families.
AB  - BACKGROUND: To our knowledge, no study has examined quality of life (QoL) among
      caregivers of individuals with schizophrenia between a developing and a developed
      country. The aim of this study was to assess QoL of the caregivers of individuals
      with schizophrenia in two countries characterized by different social, economic
      and cultural conditions, namely Chile and France. METHODS: Data were collected
      from public mental health outpatient services in Arica (Chile), and in Marseille
      (France). QoL was measured with the short-form health survey scale - 36 items
      (SF36). QoL of 41 Chilean caregivers was firstly compared with 245 French
      caregivers. Univariate and multivariate analyses using linear regression were
      then performed to determine variables potentially related to QoL scores. RESULTS:
      The caregivers were primarily mothers in the two groups, but Chilean caregivers
      were younger, and lived more frequently with the individual with schizophrenia
      than French caregivers. The SF36 scores were globally low in the two groups,
      especially on the mental QoL scores. Chilean caregivers reported lower physical
      SF36 scores than French caregivers. In the multivariate analysis, being mother
      and Chilean caregivers were the most regular features associating to a lower QoL.
      CONCLUSION: Despite differences between Chile and France, especially in terms of
      quality and quantity of mental health services and economic supports, caregivers'
      QoL levels remain particularly low for both countries. Future support programmes
      should address the specific needs of caregivers.

PMID- 22640268
TI  - Kinetics of oxidation of tyrosine by a model alkoxyl radical.
AB  - Oxidation of tyrosine moieties by radicals involved in lipid peroxidation is of
      current interest; while a rate constant has been reported for reaction of lipid
      peroxyl radicals with a tyrosine model, little is known about the reaction
      between tyrosine and alkoxyl radicals (also intermediates in the lipid
      peroxidation chain reaction). In this study, the reaction between a model alkoxyl
      radical, the tert-butoxyl radical and tyrosine was followed using steady-state
      and pulse radiolysis. Acetone, a product of the beta-fragmentation of the tert
      butoxyl radical, was measured; the yield was reduced by the presence of tyrosine
      in a concentration- and pH-dependent manner. From these data, a rate constant for
      the reaction between tert-butoxyl and tyrosine was estimated as 6 +/- 1 * 10(7)
      M(-1) s(-1) at pH 10. Tyrosine phenoxyl radicals were also monitored directly by
      kinetic spectrophotometry following generation of tert-butoxyl radicals by pulse
      radiolysis of solutions containing tyrosine. From the yield of tyrosyl radicals
      (measured before they decayed) as a function of tyrosine concentration, a rate
      constant for the reaction between tert-butoxyl and tyrosine was estimated as 7 +/
      3 * 10(7) M(-1) s(-1) at pH 10 (the reaction was not observable at pH 7). We
      conclude that reaction involves oxidation of tyrosine phenolate rather than
      undissociated phenol; since the pK(a) of phenolic hydroxyl dissociation in
      tyrosine is ~ 10.3, this infers a much lower rate constant, about 3 * 10(5) M(-1)
      s(-1), for the reaction between this alkoxyl radical and tyrosine at pH 7.4.

PMID- 22640269
TI  - Lipidized glioblastoma: pathological and molecular characteristics.
AB  - We report a rare case of a 33-year-old man with a lipidized glioblastoma
      multiforme (GBM) in the right posterior frontal region. Histologically the tumor
      had all the typical features of a GBM but with the rare observation of lipidized
      differentiation. There were multiple mitoses, extensive vascular proliferation,
      focal necrosis and the tumor cells had abundant xanthomatous cytoplasm and marked
      nuclear pleomorphism. The tumor showed immunoreactivity with GFAP. The O(6) -
      methylguanine methyltransferase (MGMT) promoter was methylated and there were no
      isocitrate dehydrogenase (IDH)1 and IDH2 mutations. To the best of our knowledge,
      this is the first time MGMT promoter status and IDH mutation assessment have been
      reported in a case of lipidized GBM.

PMID- 22640270
TI  - Effect of preeclampsia and intrauterine growth restriction on endothelial
      progenitor cells in human umbilical cord blood.
AB  - OBJECTIVES: Endothelial progenitor cells (EPCs) might play important roles in
      vascular homeostasis. This study evaluated the influence of prematurity,
      preeclampsia (PE) and intrauterine growth restriction (IUGR) on the EPC
      population in human umbilical cord blood (CB). METHODS: CB was obtained from 19
      preterm and 27 term deliveries. Mononuclear cells were isolated by gradient
      centrifugation and subjected to flow cytometry to obtain percentages of CD45(d)
      CD34+, CD45(d) CD133+, CD 45(d) CD34+ CD133+, and CD45(d) CD34+ CD133+ VEGFR-2+
      cells. Clinical data were obtained using chart review. RESULTS: Percentages of
      EPCs were comparable between preterm and term cord blood. CD45(d) CD34+ CD133+
      cells were significantly decreased in CB samples obtained from women with PE (n =
      14) [0.01, (0.00-2.6), [median, (range)], as compared to those without PE (n =
      32) [1.74 (0.00-3.1)] (p = 0.005). CD45(d) CD133+ CD34- cells were significantly
      increased in presence of PE [0.43, (0.06-1.38)], (p = 0.002). CD45(d) CD34+
      CD133+ cells were significantly decreased in presence of IUGR, with no change in
      CD45(d) CD133+ CD34- cells. Differences in EPC types associated with PE and IUGR
      were present only in term CB. CONCLUSIONS: Exposure to PE and IUGR is associated
      with significant changes in EPC population. Future studies are needed to explore
      the clinical impact of observed changes.

PMID- 22640271
TI  - Fulminant necrotizing fasciitis caused by Serratia marcescens in an
      immunosuppressed host.

PMID- 22640276
TI  - Chronic care model for the management of depression: synthesis of barriers to,
      and facilitators of, success.
AB  - Depression is a socially- and physically-disabling condition. The Chronic Care
      Model (CCM) was developed to promote better management of long-term conditions,
      such as depression, in primary care settings. The aim of the study was to
      identify barriers to, and facilitators of, success when implementing the CCM for
      the management of depression in primary care. A systematic search was conducted
      in electronic databases from January 2005 to December 2011. Thirteen articles met
      the inclusion criteria and were reviewed by means of a thematic analysis. The
      barriers were categorized under two themes: lack of organizational,
      administrative, and professional ability to change and implement the components
      of the CCM; and lack of clarity pertaining to the responsibility inherent in the
      role of care manager (often a nurse) when it comes to promoting the patient's
      self-management ability. In terms of the facilitators of success, two themes
      emerged: leadership support and vision, and redesigning the delivery system. When
      shaping an environment for organizational change, leadership and professionals
      must work towards a common goal and vision. Such processes require a care manager
      with a clear role and responsibilities in order for the health-care system to
      meet the needs of the person with depression.

PMID- 22640275
TI  - Epidermolysis bullosa simplex with mottled pigmentation: a family report and
      review.
AB  - Epidermolysis bullosa simplex with mottled hyperpigmentation (EBS-MP) is an
      uncommon subtype of EBS. Its clinical features depend on the age of diagnosis,
      and clinical variations have been described even within family members. We
      present six cases from two unrelated Spanish families each with several affected
      members with EBS-MP and review the clinical and genetic findings in all reported
      patients. We highlight the changing clinical features of the disease throughout
      life. 

PMID- 22640277
TI  - The effect of antithyroid treatment on atrial conduction times in patients with
      subclinical hyperthyroidism.
AB  - BACKGROUND: Prolonged atrial conduction time measured by tissue Doppler imaging
      (TDI) has been associated with increased risk of atrial fibrillation. We aimed to
      evaluate the effect of subclinical hyperthyroidism (SH) and antithyroid treatment
      on atrial conduction time. METHODS: A total of 30 patients with SH (26 females;
      mean age 34.8 +/- 8.5 years) and 30 age- and gender-matched controls were
      included. Using TDI, atrial conduction time was measured from the lateral mitral
      annulus, septal mitral annulus, and lateral tricuspid annulus. Intra- and
      interatrial conduction delay were calculated. TDI and thyroid hormone levels were
      studied at the time of enrollment and after achievement of euthyroid state with
      propylthiouracil treatment. Patients were followed for 14 +/- 3 weeks. RESULTS:
      Atrial conduction time at the lateral and septal mitral annulus were
      significantly higher in patients with SH compared to controls. Both inter-,
      right, and left intraatrial electromechanical delay were prolonged in patients
      with SH compared to control subjects (21.3 +/- 6.1 vs. 13.9 +/- 4.3, P < 0.001
      and 4.2 +/- 3.5 vs. 2.3 +/- 1.9, P = 0.014 and 17.1 +/- 6.0 vs. 11.6 +/- 3.8, P <
      0.001, respectively). After achievement of euthyroid state, inter- and left
      intraatrial electromechanical delay were significantly decreased compared to
      baseline values and approximated to the values of the control group (P < 0.001).
      CONCLUSION: SH is associated with prolonged atrial conduction time. After
      achievement of euthyroid state, decrement in atrial conduction time may reveal
      how the antithyroid treatment may prevent the development of atrial fibrillation
      in these patients.

PMID- 22640364
TI  - MYD88 somatic mutations in MALT lymphomas.

PMID- 22640365
TI  - The roles of word concreteness and cognitive load on interhemispheric processes
      of recognition.
AB  - Previous studies on hemispheric specialisation suggest that the cerebral
      hemispheres differ in the way verbal information is processed. There is also
      evidence that functional asymmetries are attributable to differences in stimulus
      properties and/or task complexity. To study these asymmetries in the domain of
      explicit recognition, concrete and abstract nouns were presented either in the
      right or left visual fields and recognised with foveal vision at different
      retention levels. We propose that different hemispheric mechanisms underlie the
      encoding of abstract and concrete information, which can be modulated by
      cognitive or mental load. To accomplish this goal, 92 right-handed undergraduate
      Portuguese students with normal or corrected-to-normal vision were randomly
      sampled from a university campus. The results showed that concrete words were
      discriminated better than abstract words when previously encoded in the right
      hemisphere for the longest retention interval between encoding and retrieval.
      These data suggest that there are different neural mechanisms for the semantic
      encoding of concrete and abstract concepts. The practical implications are
      discussed.

PMID- 22640366
TI  - Optimal design for the precise estimation of an interaction threshold: the impact
      of exposure to a mixture of 18 polyhalogenated aromatic hydrocarbons.
AB  - Traditional additivity models provide little flexibility in modeling the dose
      response relationships of the single agents in a mixture. While the flexible
      single chemical required (FSCR) methods allow greater flexibility, its implicit
      nature is an obstacle in the formation of the parameter covariance matrix, which
      forms the basis for many statistical optimality design criteria. The goal of this
      effort is to develop a method for constructing the parameter covariance matrix
      for the FSCR models, so that (local) alphabetic optimality criteria can be
      applied. Data from Crofton et al. are provided as motivation; in an experiment
      designed to determine the effect of 18 polyhalogenated aromatic hydrocarbons on
      serum total thyroxine (T(4)), the interaction among the chemicals was
      statistically significant. Gennings et al. fit the FSCR interaction threshold
      model to the data. The resulting estimate of the interaction threshold was
      positive and within the observed dose region, providing evidence of a dose
      dependent interaction. However, the corresponding likelihood-ratio-based
      confidence interval was wide and included zero. In order to more precisely
      estimate the location of the interaction threshold, supplemental data are
      required. Using the available data as the first stage, the Ds-optimal second
      stage design criterion was applied to minimize the variance of the hypothesized
      interaction threshold. Practical concerns associated with the resulting design
      are discussed and addressed using the penalized optimality criterion. Results
      demonstrate that the penalized Ds-optimal second-stage design can be used to more
      precisely define the interaction threshold while maintaining the characteristics
      deemed important in practice.

PMID- 22640367
TI  - Uses of crude oil as traditional medicine: a survey of mothers in a rural clinic
      in South-south Nigeria.
AB  - INTRODUCTION: Crude oil is used as traditional medicine among rural dwellers in
      South-south Nigeria. Although complications have been reported following its use,
      this rural populace holds tenaciously to an erroneous belief in its efficacy in
      treating many ailments. Despite this widespread use there are no known studies
      from the region on the use of crude oil in this way. This study surveyed the use
      of crude oil by rural mothers with the objectives of determining the proportion
      of mothers who use crude oil as traditional medicine, the reasons for its use,
      the diseases believed to be cured by it, and to establish the identity of those
      who administer crude oil. METHOD: This cross-sectional study was conducted in
      Bethesda Clinic Ngo in South- south Nigeria in the period January-December 2009.
      RESULTS: Of 420 mothers recruited, 134 (31.9%) used crude oil as medication.
      Their ages ranged from 19 to 47 years with a mean of 33.72 +/- 9.45 years.
      Mothers older than 30 years were significantly more likely to use crude oil than
      those younger than 30 years (X2= 4.56, p = 0.033, RR = 0.737, CI = 0.548-0.990).
      There was no statistically significant association between marital status and the
      use of crude oil as traditional medicine (chi2 = 1.24, p = 0.265, RR= 0.793, CI =
      0.545-1.255 ). Although the majority of participants (78.86%) had a minimum of
      primary education level (educated group), the uneducated participants were
      significantly more likely to use crude oil (chi2 = 62. 67, p < 0.001, RR = 2.936,
      CI = 2.243-3.776 ). The proportion of mothers using crude oil was significantly
      higher among those whose occupation was fishing (chi2 = 10.98, p = 0.001, RR =
      1.629, CI = 1.198-2.232 ). The most common use of crude oil was for febrile
      convulsions (82.1%). The reasons for using crude oil were that crude oil was
      inexpensive (66.4%) and that available hospitals were costly and/or inefficient
      (61.9%). The most common administrators of crude oil were neighbours (73.2%).
      CONCLUSION: A high proportion of mothers attending Bethesda Clinic Ngo use crude
      oil on their children as a traditional medicine, and this is because of their
      belief in its effectiveness, and its availability and affordability. The use of
      this product is encouraged the country's costly and inefficient health system.
      Neighbours play a large role in the administration of crude oil and this is
      consistent with the local culture.

PMID- 22640368
TI  - Host-microbe interactions that shape the pathogenesis of Acinetobacter baumannii
      infection.
AB  - Acinetobacter baumannii is an opportunistic pathogen that has emerged as a
      prevalent source of nosocomial infections, most frequently causing ventilator
      associated pneumonia. The emergence of pan-drug resistant strains magnifies the
      problem by reducing viable treatment options and effectively increasing the
      mortality rate associated with Acinetobacter infections. In light of this rising
      threat, research on A. baumannii epidemiology, antibiotic resistance, and
      pathogenesis is accelerating. The recent development of both in vitro and in vivo
      models has enabled studies probing the host-Acinetobacter interface. Bacterial
      genetic screens and comparative genomic studies have led to the identification of
      several A. baumannii virulence factors. Additionally, investigations into host
      defence mechanisms using animal models or cell culture have provided insight into
      the innate immune response to infection. This review highlights some of the key
      attributes of A. baumannii virulence with an emphasis on bacterial interactions
      with the innate immune system.

PMID- 22640369
TI  - Inferring facts from fiction: reading correct and incorrect information affects
      memory for related information.
AB  - People can acquire both true and false knowledge about the world from fictional
      stories. The present study explored whether the benefits and costs of learning
      about the world from fictional stories extend beyond memory for directly stated
      pieces of information. Of interest was whether readers would use correct and
      incorrect story references to make deductive inferences about related information
      in the story, and then integrate those inferences into their knowledge bases.
      Participants read stories containing correct, neutral, and misleading references
      to facts about the world; each reference could be combined with another reference
      that occurred in a later sentence to make a deductive inference. Later they
      answered general knowledge questions that tested for these deductive inferences.
      The results showed that participants generated and retained the deductive
      inferences regardless of whether the inferences were consistent or inconsistent
      with world knowledge, and irrespective of whether the references were placed
      consecutively in the text or separated by many sentences. Readers learn more than
      what is directly stated in stories; they use references to the real world to make
      both correct and incorrect inferences that are integrated into their knowledge
      bases.

PMID- 22640370
TI  - Anxiety-related constructs mediate the relation between age and health anxiety.
AB  - OBJECTIVE: Few studies have examined health anxiety in older adults, and it is
      unknown which factors account for age-related differences in health anxiety.
      Given similarities between health anxiety and the anxiety disorders, anxiety
      related constructs, including anxiety sensitivity, intolerance of uncertainty,
      emotion regulation, and anxiety control, were examined as mediators of the
      relation between age (older vs. young adults) and health anxiety. METHODS: Eighty
      six older adults aged 60 and older and 117 young adults aged 18 to 30 completed
      several self-report measures of health anxiety and anxiety-related constructs.
      RESULTS: Young adults reported higher levels of health anxiety than older adults.
      Anxiety sensitivity and intolerance of uncertainty partially mediated the
      relation between age and health anxiety. Perceived anxiety control, reappraisal,
      and suppression did not mediate the relation between age and health anxiety.
      CONCLUSIONS: Anxiety sensitivity and intolerance of uncertainty are predisposing
      characteristics that appear to partially explain age-related differences in
      health anxiety. These constructs may be necessary targets for assessment and
      interventions among older and young adults.

PMID- 22640371
TI  - Assessment of anti-depressant effect of nelumbinis semen on rats under chronic
      mild stress and its subchronic oral toxicity in rats and beagle dogs.
AB  - BACKGROUND: Previously, we examined the antidepressant effects of Nelumbinis
      Semen (NS). In this study, we assessed the anti-depressant effects of NS in the
      forced swimming test and chronic mild stress (CMS) models of depression and its
      oral toxicity in rats and dogs. METHODS: In the forced swimming test, NS was
      intraperitoneally injected before 24 h, 5 h and 1 h of forced swimming test. And
      the rats were forced to swim for 5 min, the duration of immobility was observed.
      In CMS models, animals were exposed to a variety of CMS for 8 weeks in order to
      induce depression-like symptoms. They were treated with NS for the last four
      weeks of the 8-week CMS and then an open field test was conducted. The anti
      depression effects were evaluated based on a measured index, which consisted of
      visiting counts, start latency, rearing number and grooming time. In the
      toxicological studies, NS was administered to rats by gavages for 13 weeks at
      doses of 0, 500, 1000, and 2000 mg/kg/day. To assess the toxicity of NS in beagle
      dogs, NS was administered orally for 28 days at doses of 0, 500, 1000, 2000 and
      4000 mg/kg/day. RESULTS: 400 mg/kg of NS had the lowest immobility times in
      forced swimming test. And NS significantly reversed the decreased visiting
      counts, rearing number and grooming time caused by CMS. In addition, NS treatment
      significantly decreased the start latency. No treatment-related toxicity was
      detected during 13 weeks administration in rats and 28 days administration in
      dogs. CONCLUSIONS: Based on the results of this study and previous reports that
      have examined the anti-depressive effects of NS, NS holds great promise for use
      in the treatment of depression without causing any adverse effects or toxicities.

PMID- 22640373
TI  - Robotic excision of atrial myxoma.
AB  - BACKGROUND: Advances in optics and instrumentation with the da Vinci S Surgical
      System have facilitated minimally invasive and robotic cardiac procedures
      including mitral valve repair and atrial myxoma excision. We report our
      retrospective data comparing robotically assisted myxoma excision with standard
      median sternotomy excision. METHODS: Data were collected for cardiac myxoma
      resection performed between January 2000 and December 2009. The resulting cohort
      included a total of 57 patients. These patients were grouped into two categories:
      robotic-assisted (n = 17) surgical procedures and traditional (nonrobotic; n =
      40) surgical procedures. Presurgical and surgical risk factors were examined.
      RESULTS: Univariate analysis comparing the surgical procedure groups and surgical
      risk factors found a significant difference in 3 of the 14 variables. Cannulation
      in all patients undergoing robotic-assisted cardiac myxoma excision was performed
      through cannulating the common femoral artery and vein while cannulation for the
      traditional procedures was performed using the aorta and atrium except for two
      patients. For aortic occlusion, 14 of the robotic-assisted cardiac myxoma
      patients had balloon occlusion and 34 of the traditional cardiac myxoma patients
      had aortic cross-clamp occlusion. Operating time was significantly shorter for
      robotic cases (2.7 hours) compared with traditional cases (3.5 hours).
      CONCLUSION: Robotic excision of atrial myxomas is safe and may be an alternative
      to traditional open surgery in selected patients.

PMID- 22640372
TI  - Osteo-cise: strong bones for life: protocol for a community-based randomised
      controlled trial of a multi-modal exercise and osteoporosis education program for
      older adults at risk of falls and fractures.
AB  - BACKGROUND: Osteoporosis affects over 220 million people worldwide, and currently
      there is no 'cure' for the disease. Thus, there is a need to develop evidence
      based, safe and acceptable prevention strategies at the population level that
      target multiple risk factors for fragility fractures to reduce the health and
      economic burden of the condition. METHODS/DESIGN: The Osteo-cise: Strong Bones
      for Life study will investigate the effectiveness and feasibility of a multi
      component targeted exercise, osteoporosis education/awareness and behavioural
      change program for improving bone health and muscle function and reducing falls
      risk in community-dwelling older adults at an increased risk of fracture. Men and
      women aged >=60 years will participate in an 18-month randomised controlled trial
      comprising a 12-month structured and supervised community-based program and a 6
      month 'research to practise' translational phase. Participants will be randomly
      assigned to either the Osteo-cise intervention or a self-management control
      group. The intervention will comprise a multi-modal exercise program
      incorporating high velocity progressive resistance training, moderate impact
      weight-bearing exercise and high challenging balance exercises performed three
      times weekly at local community-based fitness centres. A behavioural change
      program will be used to enhance exercise adoption and adherence to the program.
      Community-based osteoporosis education seminars will be conducted to improve
      participant knowledge and understanding of the risk factors and preventative
      measures for osteoporosis, falls and fractures. The primary outcomes measures, to
      be collected at baseline, 6, 12, and 18 months, will include DXA-derived hip and
      spine bone mineral density measurements and functional muscle power (timed stair
      climb test). Secondary outcomes measures include: MRI-assessed distal femur and
      proximal tibia trabecular bone micro-architecture, lower limb and back maximal
      muscle strength, balance and function (four square step test, functional reach
      test, timed up-and-go test and 30-second sit-to-stand), falls incidence and
      health-related quality of life. Cost-effectiveness will also be assessed.
      DISCUSSION: The findings from the Osteo-cise: Strong Bones for Life study will
      provide new information on the efficacy of a targeted multi-modal community-based
      exercise program incorporating high velocity resistance training, together with
      an osteoporosis education and behavioural change program for improving multiple
      risk factors for falls and fracture in older adults at risk of fragility
      fracture. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      reference ACTRN12609000100291.

PMID- 22640374
TI  - Tempest: GPU-CPU computing for high-throughput database spectral matching.
AB  - Modern mass spectrometers are now capable of producing hundreds of thousands of
      tandem (MS/MS) spectra per experiment, making the translation of these
      fragmentation spectra into peptide matches a common bottleneck in proteomics
      research. When coupled with experimental designs that enrich for post
      translational modifications such as phosphorylation and/or include isotopically
      labeled amino acids for quantification, additional burdens are placed on this
      computational infrastructure by shotgun sequencing. To address this issue, we
      have developed a new database searching program that utilizes the massively
      parallel compute capabilities of a graphical processing unit (GPU) to produce
      peptide spectral matches in a very high throughput fashion. Our program, named
      Tempest, combines efficient database digestion and MS/MS spectral indexing on a
      CPU with fast similarity scoring on a GPU. In our implementation, the entire
      similarity score, including the generation of full theoretical peptide candidate
      fragmentation spectra and its comparison to experimental spectra, is conducted on
      the GPU. Although Tempest uses the classical SEQUEST XCorr score as a primary
      metric for evaluating similarity for spectra collected at unit resolution, we
      have developed a new "Accelerated Score" for MS/MS spectra collected at high
      resolution that is based on a computationally inexpensive dot product but
      exhibits scoring accuracy similar to that of the classical XCorr. In our
      experience, Tempest provides compute-cluster level performance in an affordable
      desktop computer.

PMID- 22640375
TI  - Integrated project views: decision support platform for drug discovery project
      teams.
AB  - Drug discovery teams continuously have to decide which compounds to progress and
      which experiments to perform next, but the data required to make informed
      decisions is often scattered, inaccessible, or inconsistent. In particular, data
      tend to be stored and represented in a compound-centric or assay-centric manner
      rather than project-centric as often needed for effective use in drug discovery
      teams. The Integrated Project Views (IPV) system has been created to fill this
      gap; it integrates and consolidates data from various sources in a project
      oriented manner. Its automatic gathering and updating of project data not only
      ensures that the information is comprehensive and available on a timely basis,
      but also improves the data consistency. Due to the lack of suitable off-the-shelf
      solutions, we were prompted to develop custom functionality and algorithms geared
      specifically to our drug discovery decision making process. In 10 years of usage,
      the resulting IPV application has become very well-accepted and appreciated,
      which is perhaps best evidenced by the observation that standalone Excel
      spreadsheets are largely eliminated from project team meetings.

PMID- 22640377
TI  - Efficient targeted mutagenesis of the chordate  Ciona intestinalis genome with
      zinc-finger nucleases.
AB  - Zinc-finger nucleases (ZFNs) are engineered nucleases that induce DNA double
      strand breaks (DSBs) at target sequences. They have been used as tools for
      generating targeted mutations in the genomes of multiple organisms in both
      animals and plants. The DSB induced by ZFNs is repaired by non-homologous end
      joining (NHEJ) or by homologous recombination (HR) mechanisms. Non-homologous end
      joining induces some errors because it is independent of a reference DNA
      sequence. Through the NHEJ mechanism, ZFNs generate insertional or deletional
      mutations at the target sequence. We examined the usability, specificity and
      toxicity of ZFNs in the basal chordate Ciona intestinalis. As the target of ZFNs,
      we chose an enhanced green fluorescent protein (EGFP) gene artificially inserted
      in the C. intestinalis genome because this locus is neutral for the development
      and growth of C. intestinalis, and the efficiency of mutagenesis with ZFNs can
      thus be determined without any bias. We introduced EGFP -ZFN mRNAs into the
      embryos of an EGFP -transgenic line and observed the mutation frequency in the
      target site of EGFP . We also examined the effects of the EGFP -ZFNs at off
      target sites resembling the EGFP target sequence in the C. intestinalis genome in
      order to examine the specificity of ZFNs. We further investigated the influence
      of ZFNs on embryogenesis, and showed that adequate amounts of ZFNs, which do not
      disrupt embryogenesis, can efficiently induce mutations on the on-target site
      with less effect on the off-target sites. This suggests that target mutagenesis
      with ZFNs will be a powerful technique in C. intestinalis.

PMID- 22640376
TI  - The association between the preoperative serum levels of lipocalin-2 and matrix
      metalloproteinase-9 (MMP-9) and prognosis of breast cancer.
AB  - BACKGROUND: Although a number of experimental studies have suggested the role of
      lipocalin-2 (LCN2) and matrix metalloproteinase-9 (MMP-9) in breast cancer
      progression, limited numbers of epidemiological studies have examined the
      relationship between the levels of lipocalin-2 and MMP-9 and breast cancer
      survival. METHODS: Preoperative serum levels of lipocalin-2 and MMP-9 were
      measured in 303 breast cancer patients and 74 healthy controls recruited between
      2004 and 2007. We examined the association between lipocalin-2 and MMP-9 levels
      and disease-free survival (DFS) using Cox proportional hazard regression model.
      RESULTS: The serum levels of lipocalin-2 and MMP-9 were not significantly
      different between patients and controls (P > 0.05). Elevated lipocalin-2 and MMP
      9 levels were associated with reduced DFS of breast cancer ( Ptrend = 0.029 and
      Ptrend = 0.063, respectively). When lipocalin-2 and MMP-9 levels were categorized
      based on the combined risk score, patients with higher levels of both lipocalin-2
      and MMP-9 exhibited poor DFS compared to patients with lower levels (Ptrend =
      0.004). Furthermore, these effects were profound in patients with BMI less than
      25 kg/m2 (adjusted hazard ratio (aHR), 3.17; 95% confidence intervals (CI), 1.66
      6.06, Ptrend < 0.001) or lymph-node negative breast cancer (aHR, 5.36; 95% CI,
      2.18-13.2, Ptrend < 0.001). CONCLUSIONS: Our study suggests that the elevated
      levels of lipocalin-2 and MMP-9 are associated with reduced breast cancer
      survival, particularly in patients with lower BMI and lymph-node negative breast
      cancers.

PMID- 22640378
TI  - Youth mental health reform and early intervention: encouraging early signs.

PMID- 22640379
TI  - Beyond early intervention: can we adopt alternative narratives like
      'Woodshedding' as pathways to recovery in schizophrenia?
AB  - AIM: To consider how early intervention in psychosis can support a recovery
      paradigm. METHODS: Significant numbers of those developing a first episode of
      psychosis are on a path to a persisting and potentially life long condition.
      Constituting the schizophrenia spectrum disorders, such conditions demand the
      particular qualities and attitudes inherent within recovery-based practice. This
      paper explores some of these qualities and attitudes by examining the tension
      between a traditional 'clinical' narrative used by many health providers and a
      'human' narrative of users of services and their families. RESULTS: We draw out
      key features and constructs of recovery practice as they relate to the EI
      paradigm. These include: woodshedding, turning points, discontinuous improvement
      models, therapeutic optimism, gradualism and narratives of story telling. We also
      highlight the role of family members and other close supporters and believe their
      potential contribution requires greater consideration. CONCLUSIONS: The early
      intervention (EI) paradigm can resonate and indeed offer a stronghold for
      recovery-based practice where traditional mental health services have sometimes
      struggled. Conversely, failure of caregivers to provide such an approach in the
      early phase of illness can cause unnecessary and sometimes disastrous
      consequences.

PMID- 22640380
TI  - A partnership model of early intervention in psychosis programme--a Canadian
      experience.
AB  - AIM: To describe how a new partnership model of early intervention in psychosis,
      early intervention in psychosis (EIP) programme delivery in Canada attracted the
      interest of the community and acquired government funding. METHODS: The process
      by which a few individuals used a conceptual framework of integrated,
      collaborative, flexible and recovery focused principles to engage community
      partners and attract government funding is described. RESULTS: The establishment
      of a small EIP programme and its expansion to a regional programme serving an
      area of 20,000 square kilometers and a population of approximately 500,000 people
      were achieved. A programme specific logic prototype was developed. A synergy of
      public, private and academic services emerged with an infrastructure for ongoing
      cohesiveness and productivity. Annual clinic visits increased from 641 in 2002 to
      1904 in 2007 and annual new patients enrollments grew from 46 to 128 within the
      same period. Staffing grew from an interdisciplinary staff of 1.5 full-time
      equivalent (FTE) to the current 10.0 FTE. CONCLUSIONS: A carefully orchestrated
      programme organization that is inclusive rather than exclusive can produce a
      balance of evidence-based best practices in client focused service, community
      mental health integration and academic productivity.

PMID- 22640381
TI  - Paediatric major depressive disorder: neurobiology and implications for early
      intervention.
AB  - AIM: Paediatric major depressive disorder (MDD) is associated with chronicity and
      poor outcomes. The goals of this review are (i) to integrate how developing
      biological systems contribute to the pathophysiology of paediatric MDD, and (ii)
      to consider the role of early intervention for depressed youth. METHODS: A
      developmental perspective is applied herein to review and integrate key
      neurobiological systems that are implicated in paediatric MDD. We also review
      recent treatment research for adolescents with MDD. RESULTS: Available evidence
      in paediatric and adult populations support an integrative model for the
      pathophysiology of MDD that involves fronto-limbic neural circuitry and the
      neuroendocrine stress response system. Evidence from treatment research supports
      the efficacy of available treatments modalities, including antidepressant
      medications, cognitive behavioral therapy, and their combination, for the
      majority of adolescents with moderate to severe MDD. CONCLUSIONS: Since the
      biological systems implicated in MDD mature through adolescence, adolescents may
      be more susceptible to developing depression but also may be more amenable to
      treatment interventions. Early identification and treatment of paediatric MDD may
      be able to divert negative trajectories and lead to improved outcomes.

PMID- 22640382
TI  - Differential brain activation during response inhibition in bipolar and attention
      deficit hyperactivity disorders.
AB  - AIM: To identify differential patterns of brain activation between adolescents
      with bipolar disorder and adolescents with attention-deficit hyperactivity
      disorder (ADHD) to better understand the neurophysiology of both disorders. We
      hypothesized that subjects with ADHD would show altered activation in brain
      regions involved in executive and sustained attention. In contrast, we
      hypothesized that bipolar subjects would show altered brain activation in regions
      responsible for emotionally homeostasis, including the striatum and amygdala.
      METHODS: Functional magnetic resonance imaging was performed during a continuous
      performance task with a response inhibition component in 11 adolescents with
      bipolar disorder during a manic episode, 10 adolescents with ADHD, and 13 healthy
      adolescents. RESULTS: There were no differences in behavioural performance among
      the three groups. Compared with bipolar subjects, subjects with ADHD showed
      increased activation in the superior temporal lobe during successful response
      inhibition. Although bipolar subjects did not show activation differences in the
      striatum or amygdala compared with ADHD subjects, increased left parahippocampal
      activation in the bipolar group was associated with increased manic symptoms.
      CONCLUSIONS: The patterns of brain activation observed in the current study
      support divergent patterns of neurophysiological dysfunction in individuals with
      bipolar disorder as compared with those with ADHD. Therefore, the impulsive
      behaviour seen in both disorders may be the consequence of dysfunction in
      different brain regions, and further research may help identify neurobiological
      markers that are specific to each condition.

PMID- 22640383
TI  - Lifetime history of substance misuse in first-episode psychosis: prevalence and
      its influence on psychopathology and onset of psychotic symptoms.
AB  - INTRODUCTION: Substance misuse (SM) (drug/alcohol dependence or abuse) in
      psychotic illness is an increasingly recognized problem. We aimed to estimate the
      prevalence and examine the influence of SM on age at onset of psychosis and
      psychopathology among patients with first-episode psychosis. METHOD: One hundred
      seventy-one consecutive patients with first-episode psychosis were assessed. SM,
      age of onset of psychosis and psychopathology were determined using valid
      instruments. RESULTS: Seventy-seven (46%) patients had a lifetime history of SM
      and were predominately males, had more positive symptoms, and in the majority of
      cases (84%), started misusing substances before the onset of psychosis (SM-BP).
      There was no difference in age of onset between patients with SM-BP and the rest
      of the sample. CONCLUSION: Lifetime history of SM is common and may influence
      psychopathology, but does not appear to influence or bring forward the age at
      onset of psychotic symptoms.

PMID- 22640384
TI  - Engagement and early termination of contact with a community-based early
      intervention service for personality disorder in young adults.
AB  - BACKGROUND: Few studies have examined factors associated with continuity of care
      in a community-based early intervention service for personality disorder in
      patients aged 16-25. AIMS: To estimate the probability of dropping out of care in
      patients attending an early intervention service for personality disorder and
      identify patient characteristics associated with those who drop out, are
      discharged or continue using the service. METHOD: A 24-month cohort of first
      contact patients attending the early intervention service was followed up for 12
      months to identify drop-outs, discharges and those still using the service.
      RESULTS: One hundred eighty-three first contact patients were referred/self
      referred during the study timescale. After 12-month follow-up, 83 (45%) were
      discharged, 39 (21%) still using the service and 61 (33%) dropped out. Drop out
      was most likely among patients aged 21-25, from higher socio-economic groups and
      highest during months 3-5 of service use. No discharges occurred until at least 3
      months into the service, with a peak at 6-8 months. CONCLUSIONS: Although sharing
      many factors predicting increased levels of drop-out, the rate of drop-out among
      young adults aged between 16-25 attending an early intervention service for
      personality disorder was equivalent to that experienced by services for adults
      with a long history of personality disorder diagnosis. Concerns exist, however,
      concerning increased rates of drop-out among patients reporting a greater number
      of difficulties, reporting a common mental health or substance abuse problem, and
      during months 3-5 of service use. Implications of the results for future service
      developments are discussed.

PMID- 22640385
TI  - Do premorbid impairments predict emergent 'prodromal' symptoms in young relatives
      at risk for schizophrenia?
AB  - AIMS: Individuals at risk for developing schizophrenia (SZ) in the future
      frequently exhibit subtle behavioural and neurobiological abnormalities in their
      childhood. A better understanding of the role of these abnormalities in
      predicting later onset of 'prodromal' symptoms or psychosis may help in early
      identification of SZ. METHODS: In an ongoing prospective follow-up study of young
      genetically at-risk relatives of patients with SZ, we studied the prevalence of
      problems in premorbid social adjustment and childhood psychopathology and
      examined their relationship with the presence and progression of 'prodromal'
      symptoms of SZ. RESULTS: Growth curve analyses showed that 'prodromal' symptoms,
      as measured by the Scale of 'Prodromal' Symptoms, increased during follow-up.
      Premorbid maladjustment and childhood behavioural disturbances were cross
      sectionally correlated broadly with 'prodromal' symptomatology scores.
      Longitudinal analyses revealed that behavioural disturbances, but not childhood
      maladjustment at baseline, significantly predicted increases in 'prodromal'
      symptomatology during the 2-year study period. CONCLUSION: Premorbid behavioural
      disturbance and maladjustment may predict the later emergence of 'prodromal'
      symptoms. 'Prodromal' symptoms in young at-risk relatives may define a subgroup
      worthy of follow-up into the age of risk for psychosis in order to cost
      effectively characterize the predictors of psychotic symptoms and SZ.

PMID- 22640386
TI  - Substance misuse over the first 18 months of specialized intervention for first
      episode psychosis.
AB  - AIM: Examine substance misuse over the first 18 months of first-episode psychosis
      treatment. METHOD: Clinicians rated alcohol and drug (mostly cannabis) misuse for
      243 individuals followed prospectively. Assessments were completed at baseline
      and after 3, 6 and 18 months. Interventions relating to substance misuse included
      ongoing assessment of use, education and counselling to avoid. RESULTS: Alcohol
      and drug misuse declined significantly between baseline and 3 months, especially
      among patients with a substance abuse or dependence diagnosis at baseline.
      Overall, these reductions were maintained over the 18-month follow-up period. The
      exception was worsening alcohol misuse over time among patients with alcohol
      abuse or dependence on entry. CONCLUSIONS: With good usual care, education and
      support, alcohol and drug misuse declined significantly during the first months
      of psychosis treatment. The improvements in drug misuse were generally maintained
      over the 18-month follow-up, and worsening alcohol misuse over time may be the
      greater issue.

PMID- 22640387
TI  - Obstetric complications and risk for conversion to psychosis among individuals at
      high clinical risk.
AB  - AIM: Examining risk factors among high-risk populations stands to inform
      treatment and to elucidate our understanding of the pathophysiology of
      schizophrenia. Despite substantial evidence implicating the incidence of
      obstetric complications (OCs) as a risk factor for schizophrenia, little is known
      about the relationship between OCs and risk for conversion among high-risk
      individuals. METHODS: We prospectively followed individuals at high risk for
      developing psychotic disorders for a two-year period to determine if a history of
      OCs is associated with conversion. RESULTS: Individuals who converted to
      psychosis had significantly more OCs when compared to non-converting
      participants; a history of OCs was associated with increased odds of conversion
      (odds ratio = 4.90, confidence interval :1.04/22.20). OCs were positively
      associated with prodromal symptomatology. CONCLUSIONS: To date, this report
      represents the first empirical evidence suggesting that OCs confer increased risk
      of conversion to psychosis. It is possible that OCs interact with brain
      maturational processes in the pathophysiology of schizophrenia and can serve as a
      risk marker.

PMID- 22640388
TI  - The Somerset team for early psychosis.
AB  - AIM: To describe the development of an early intervention (EI) service in
      Somerset, and evaluate the progress after the first 2 years. METHOD: The Somerset
      Team for Early Psychosis (STEP) has been developed in stages from 2003 to the
      present 'hub-and-spoke' model. The framework, which the team operates, is
      outlined, the assessment and outcome measures are presented, and the
      interventions, with the emphasis on working with families, are discussed.
      RESULTS: Two hundred fifty-nine referrals have been received in the first 2
      years, with the caseload currently standing at 153. The mean duration of
      untreated psychosis of STEP clients was just over 9 months; when those who
      developed psychosis before 2004 (pre-STEP) were removed, this was reduced to 6.4
      months. Eighty-four per cent of STEP clients have had their families involved
      with our service in some way. Relapse rates of clients in the service for over 12
      months have been encouragingly low (17%). CONCLUSIONS: We reflect on the
      challenges faced in relation to the EI service model described in the Department
      of Health's Policy Implementation Guide and, in particular, on having
      successfully built on the existing family interventions service.

PMID- 22640391
TI  - The neural basis of vivid memory is patterned on perception.
AB  - When we have a rich and vivid memory for a past experience, it often feels like
      we are transported back in time to witness once again this event. Indeed, a
      perfect memory would exactly mimic the experiential quality of direct sensory
      perception. We used fMRI and multivoxel pattern analysis to map and quantify the
      similarity between patterns of activation evoked by direct perception of a
      diverse set of short video clips and the vivid remembering, with closed eyes, of
      these clips. We found that the patterns of distributed brain activation during
      vivid memory mimicked the patterns evoked during sensory perception. Using whole
      brain patterns of activation evoked by perception of the videos, we were able to
      accurately classify brain patterns that were elicited when participants tried to
      vividly recall those same videos. A discriminant analysis of the activation
      patterns associated with each video revealed a high degree (explaining over 80%
      of the variance) of shared representational similarity between perception and
      memory. These results show that complex, multifeatured memory involves a partial
      reinstatement of the whole pattern of brain activity that is evoked during
      initial perception of the stimulus.

PMID- 22640390
TI  - FM-selective networks in human auditory cortex revealed using fMRI and
      multivariate pattern classification.
AB  - Frequency modulation (FM) is an acoustic feature of nearly all complex sounds.
      Directional FM sweeps are especially pervasive in speech, music, animal
      vocalizations, and other natural sounds. Although the existence of FM-selective
      cells in the auditory cortex of animals has been documented, evidence in humans
      remains equivocal. Here we used multivariate pattern analysis to identify
      cortical selectivity for direction of a multitone FM sweep. This method
      distinguishes one pattern of neural activity from another within the same ROI,
      even when overall level of activity is similar, allowing for direct
      identification of FM-specialized networks. Standard contrast analysis showed that
      despite robust activity in auditory cortex, no clusters of activity were
      associated with up versus down sweeps. Multivariate pattern analysis
      classification, however, identified two brain regions as selective for FM
      direction, the right primary auditory cortex on the supratemporal plane and the
      left anterior region of the superior temporal gyrus. These findings are the first
      to directly demonstrate existence of FM direction selectivity in the human
      auditory cortex.

PMID- 22640392
TI  - Striatal dopamine influences the default mode network to affect shifting between
      object features.
AB  - Cognitive flexibility or the ability to change behavior in response to external
      cues is conceptualized as two processes: one for shifting between perceptual
      features of objects and another for shifting between the abstract rules governing
      the selection of these objects. Object and rule shifts are believed to engage
      distinct anatomical structures and functional processes. Dopamine activity has
      been associated with cognitive flexibility, but patients with dopaminergic
      deficits are not impaired on all tasks assessing cognitive flexibility,
      suggesting that dopamine may have different roles in the shifting of objects and
      rules. The goals of this study were to identify brain regions supporting object
      and rule shifts and to examine the role of dopamine in modulating these two forms
      of cognitive flexibility. Sixteen young, healthy volunteers underwent fMRI while
      performing a set-shift task designed to differentiate shifting between object
      features from shifting between abstract task rules. Participants also underwent
      PET with 6-[18F]-fluoro-l-m-tyrosine (FMT), a radiotracer measuring dopamine
      synthesis capacity. Shifts of abstract rules were not associated with activation
      in any brain region, and FMT uptake did not correlate with rule shift
      performance. Shifting between object features deactivated the medial PFC and the
      posterior cingulate and activated the lateral PFC, posterior parietal areas, and
      the striatum. FMT signal in the striatum correlated negatively with object shift
      performance and deactivation in the medial PFC, a component of the default mode
      network, suggesting that dopamine influences object shifts via modulation of
      activity in the default mode network.

PMID- 22640393
TI  - Erythema multiforme in a newborn associated with acute acquired cytomegalovirus
      infection.
AB  - Erythema multiforme is exceptional in newborns, and none of the few available
      reports has revealed a clear etiologic agent, not even herpes simplex virus.
      Immunocompetent patients rarely present with cutaneous cytomegalovirus
      involvement, and few cases of cytomegalovirus-associated erythema multiforme have
      been described, none of them in newborns. We report the first case of erythema
      multiforme in a newborn associated with cytomegalovirus infection. 

PMID- 22640394
TI  - Multiple folding states and disorder of ribosomal protein SA, a membrane receptor
      for laminin, anticarcinogens, and pathogens.
AB  - The human ribosomal protein SA (RPSA) is a multilocus protein, present in most
      cellular compartments. It is a multifunctional protein, which belongs to the
      ribosome but is also a membrane receptor for laminin, growth factors, prion,
      pathogenic microorganisms, toxins, and the anticarcinogen epigallocatechin
      gallate. It contributes to the crossing of the blood-brain barrier by neurotropic
      viruses and bacteria and is used as a biomarker of metastasis. RPSA includes an N
      terminal domain, which is homologous to the prokaryotic ribosomal proteins S2,
      and a C-terminal extension, which is conserved in vertebrates. The structure of
      its N-domain has been determined from crystals grown at 17  degrees C. The
      structure of its C-domain remains unknown. We produced in Escherichia coli and
      purified the full-length RPSA and its N- and C-domains. We characterized the
      folding states of these recombinant proteins mainly by methods of fluorescence
      and circular dichroism spectrometry, in association with quantitative analyses of
      their unfolding equilibria, induced with heat or urea. The necessary equations
      were derived from first principles. The results showed that the N-domain unfolded
      according to a three-state equilibrium. The monomeric intermediate was
      predominant at the body temperature of 37  degrees C. It also existed in the full
      length RPSA and bound ANS, a small fluorescent molecule. The C-domain was in an
      intrinsically disordered state. The recombinant N- and C-domains weakly
      interacted together. These results indicated a high plasticity of RPSA, which
      could be important for its multiple cellular localizations and functional
      interactions.

PMID- 22640395
TI  - Problems with the new brain.

PMID- 22640396
TI  - Pulmonary hemorrhage in very low-birthweight infants: risk factors and
      management.
AB  - BACKGROUND: Beginning 2007, the intratracheal route of epinephrine to end massive
      pulmonary hemorrhage (MPH) in very low-birthweight (VLBW) infants was modified at
      Kaohsiung Veterans General Hospital. The aim of the present study was to assess
      the change in outcomes for these infants, and to evaluate the risk factors of
      MPH. METHODS: Using the database of the Premature Baby Foundation of Taiwan, the
      mortality, risk factors and characteristics of VLBW infants with or without MPH
      were compared between 2000-2006 and 2007-2010. RESULTS: Between January 2000 and
      December 2010, 399 VLBW infants were admitted to Kaohsiung Veterans General
      Hospital. Mean birthweight (BW) was 1099.6 +/- 272.7 g, and mean gestational age
      (GA) was 28.7 +/- 2.9 weeks. The overall survival rate was 84.2%. Sixteen (4%)
      had MPH: 11 in the first group (2000-2006; 18.2% survival rate), and five in the
      second group (2007-2010; 80% survival rate; P= 0.0000002). Infants with MPH had
      lower mean BW (864.9 +/- 301.4 g, P= 0.0004), smaller mean GA (26.1 +/- 2.0
      weeks, P= 0.0002), significantly lower Apgar scores at 1 and 5 min, higher
      severity of respiratory distress syndrome (RDS; grades 3 or 4), and greater use
      of surfactant than infants without MPH. They also had more intraventricular
      hemorrhage and higher mortality. CONCLUSIONS: Smaller GA, lower BW, lower Apgar
      scores at 1 and 5 min, severe RDS (grades 3 or 4), and use of surfactant place
      VLBW infants at greater risk of MPH. Proper prenatal care and preventing
      premature labor and delivery were the most important preventative factors. A
      quick, deep thrust of intratracheal epinephrine with a catheter may improve
      survival.

PMID- 22640397
TI  - Above and beyond emotional valence: the unique contribution of central and
      traumatic shame memories to psychopathology vulnerability.
AB  - This paper explores whether shame memories have a distinct impact on emotional
      difficulties and psychopathology that goes beyond their negative emotional
      valence. Study 1 (N=292) investigates the contribution of centrality of shame
      memory, in comparison to the centrality of fear and sadness memories, to explain
      the memory's traumatic impact, shame, depression, anxiety, stress, paranoid, and
      dissociative symptoms. Study 2 (N=192) explores the impact of shame traumatic
      memory on shame and depression, anxiety, and stress symptoms, in comparison to
      fear and sadness traumatic memories. Both studies used undergraduate student
      samples. Results show that shame memories' centrality and traumatic features made
      an independent contribution to current external and internal shame and distinct
      psychopathological symptoms, after controlling for the effect of fear and
      sadness, centrality, and traumatic qualities. Moreover, shame memories'
      centrality and traumatic features were the best global predictors of external and
      internal shame and depressive symptoms. Centrality of shame memories was also the
      only significant predictor of paranoid ideation and dissociation. These results
      offer novel perspectives on the nature of shame and its relation to
      psychopathology, emphasising the distinct role of shame memories in human
      functioning and suffering, which goes above and beyond its negative emotional
      valence.

PMID- 22640398
TI  - An electronic health record-enabled obesity database.
AB  - BACKGROUND: The effectiveness of weight loss therapies is commonly measured using
      body mass index and other obesity-related variables. Although these data are
      often stored in electronic health records (EHRs) and potentially very accessible,
      few studies on obesity and weight loss have used data derived from EHRs. We
      developed processes for obtaining data from the EHR in order to construct a
      database on patients undergoing Roux-en-Y gastric bypass (RYGB) surgery. METHODS:
      Clinical data obtained as part of standard of care in a bariatric surgery program
      at an integrated health delivery system were extracted from the EHR and deposited
      into a data warehouse. Data files were extracted, cleaned, and stored in research
      datasets. To illustrate the utility of the data, Kaplan-Meier analysis was used
      to estimate length of post-operative follow-up. RESULTS: Demographic, laboratory,
      medication, co-morbidity, and survey data were obtained from 2028 patients who
      had undergone RYGB at the same institution since 2004. Pre-and post-operative
      diagnostic and prescribing information were available on all patients, while
      survey laboratory data were available on a majority of patients. The number of
      patients with post-operative laboratory test results varied by test. Based on
      Kaplan-Meier estimates, over 74% of patients had post-operative weight data
      available at 4 years. CONCLUSION: A variety of EHR-derived data related to
      obesity can be efficiently obtained and used to study important outcomes
      following RYGB.

PMID- 22640399
TI  - Antibiotic prescribing in primary care, adherence to guidelines and unnecessary
      prescribing--an Irish perspective.
AB  - BACKGROUND: Information about antibiotic prescribing practice in primary care is
      not available for Ireland, unlike other European countries. The study aimed to
      ascertain the types of antibiotics and the corresponding conditions seen in
      primary care and whether general practitioners (GPs) felt that an antibiotic was
      necessary at the time of consultation. This information will be vital to inform
      future initiatives in prudent antibiotic prescribing in primary care. METHODS:
      Participating GPs gathered data on all antibiotics prescribed by them in 100
      consecutive patients' consultations as well as data on the conditions being
      treated and whether they felt the antibiotic was necessary. RESULTS: 171 GPs
      collected data on 16,899 consultations. An antibiotic was prescribed at 20.16% of
      these consultations. The majority were prescribed for symptoms or diagnoses
      associated with the respiratory system; the highest rate of prescribing in these
      consultations were for patients aged 15-64 years (62.23%). There is a high rate
      of 2nd and 3rd line agents being used for common ailments such as otitis media
      and tonsillitis. Amoxicillin, which is recommended as 1st line in most common
      infections, was twice as likely to be prescribed if the prescription was for
      deferred used or deemed unnecessary by the GP. CONCLUSION: The study demonstrates
      that potentially inappropriate prescribing is occurring in the adult population
      and the high rate of broad-spectrum antimicrobial agents is a major concern. This
      study also indicates that amoxicillin may be being used for its placebo effect
      rather than specifically for treatment of a definite bacterial infection.

PMID- 22640401
TI  - Assessment of the diagnostic sensitivity and specificity of an indirect ELISA kit
      for the diagnosis of Brucella ovis infection in rams.
AB  - BACKGROUND: Brucella ovis causes an infectious disease responsible for
      infertility and subsequent economic losses in sheep production. The standard
      serological test to detect B. ovis infection in rams is the complement fixation
      test (CFT), which has imperfect sensitivity and specificity in addition to
      technical drawbacks. Other available tests include the indirect enzyme-linked
      immunosorbent assays (I-ELISA) but no I-ELISA kit has been fully evaluated.The
      study aimed to compare an I-ELISA kit and the standard CFT. Our study was carried
      out on serum samples from 4599 rams from the South of France where the disease is
      enzootic. A Bayesian approach was used to estimate tests characteristics
      (diagnostic sensitivity, Se and diagnostic specificity, Sp). The tests were then
      studied together in order to optimise testing strategies to detect B. ovis.
      RESULTS: After optimising the cut-off values in order to avoid doubtful results
      without deteriorating the concordance between the results of the two tests, the I
      ELISA appeared to be slightly more sensitive than CFT (Se I-ELISA=0.917 [0.822;
      0.992], 95% Credibility Interval (CrI) compared to Se CFT=0.860 [0.740; 0.967],
      95% CrI). However, CFT was slightly more specific than I-ELISA (Sp CFT=0.988
      [0.947; 1.0], 95% CrI) compared to Sp I-ELISA =0.952 [0.901; 1.0], 95% CrI).The
      tests were then associated with two different interpretation schemes. The series
      association increased the specificity of screening and could be used for pre
      movement testing in rams from uninfected flocks. The parallel association
      increased sequence sensitivity, thus appearing more suitable for eradicating the
      disease in infected flocks. CONCLUSIONS: The high sensitivity and acceptable
      specificity of this I-ELISA kit support its potential interest to avoid the
      limitations of CFT. The two tests could also be used together or combined with
      other diagnostic methods such as semen culture to improve the testing strategy.
      The choice of test sequence and interpretation criteria depends on the
      epidemiological context, screening objectives and the financial and practical
      constraints.

PMID- 22640402
TI  - The anticancer effect of saffron in two p53 isogenic colorectal cancer cell
      lines.
AB  - BACKGROUND: Saffron extract, a natural product, has been shown to induce
      apoptosis in several tumor cell lines. Nevertheless, the p53-dependency of
      saffron's mechanism of action in colon cancer remains unexplored. MATERIAL AND
      METHODS: In order to examine saffron's anti-proliferative and pro-apoptotic
      effects in colorectal cancer cells, we treated two p53 isogenic HCT116 cell lines
      (HCT wildtype and HCT p53-/-) with different doses of the drug and analyzed cell
      proliferation and apoptosis in a time-dependent manner. MTT viability and crystal
      violet assays were performed in order to determine the effective dose of saffron
      on both cell lines. The cell cycle progress was examined by Flow cytometric
      analysis. Apoptosis was assessed using Annexin-PI-staining and Western Blotting
      for caspase 3 and PARP cleavage. Autophagy was determined by Western Blotting of
      the light chain 3 (LC3)-II and Beclin 1 proteins. The protein content of phospho
      H2AX (gammaH2AX), a sensor of DNA double strand breaks, was also analyzed by
      Western Blotting. RESULTS: Saffron extract induced a p53-dependent pattern of
      cell cycle distribution with a full G2/M stop in HCT116 p53 wildtype cells.
      However, it induced a remarkable delay in S/G2 phase transit with entry into
      mitosis in HCT116 p53 -/- cells. The apoptotic Pre-G1 cell fraction as well as
      Annexin V staining and caspase 3 cleavage showed a more pronounced apoptosis
      induction in HCT116 p53 wildtype cells. Obviously, the significantly higher DNA
      damage, reflected by gammaH2AX protein levels in cells lacking p53, was coped by
      up-regulation of autophagy. The saffron-induced LC3-II protein level was a
      remarkable indication of the accumulation of autophagosomes, a response to the
      cellular stress condition of drug treatment. CONCLUSIONS: This is the first study
      showing the effect of saffron in HCT116 colorectal cancer cells with different
      p53 status. Saffron induced DNA-damage and apoptosis in both cell lines. However,
      autophagy has delayed the induction of apoptosis in HCT116 p53 -/- cells.
      Considering the fact that most tumors show a functional p53 inactivation, further
      research is needed to elucidate the long-term effects of saffron in p53 -/-
      tumors.

PMID- 22640403
TI  - Cherubism: best clinical practice.
AB  - Cherubism is a skeletal dysplasia characterized by bilateral and symmetric fibro
      osseous lesions limited to the mandible and maxilla. In most patients, cherubism
      is due to dominant mutations in the SH3BP2 gene on chromosome 4p16.3. Affected
      children appear normal at birth. Swelling of the jaws usually appears between 2
      and 7 years of age, after which, lesions proliferate and increase in size until
      puberty. The lesions subsequently begin to regress, fill with bone and remodel
      until age 30, when they are frequently not detectable.Fibro-osseous lesions,
      including those in cherubism have been classified as quiescent, non-aggressive
      and aggressive on the basis of clinical behavior and radiographic findings.
      Quiescent cherubic lesions are usually seen in older patients and do not
      demonstrate progressive growth. Non-aggressive lesions are most frequently
      present in teenagers. Lesions in the aggressive form of cherubism occur in young
      children and are large, rapidly growing and may cause tooth displacement, root
      resorption, thinning and perforation of cortical bone.Because cherubism is
      usually self-limiting, operative treatment may not be necessary. Longitudinal
      observation and follow-up is the initial management in most cases. Surgical
      intervention with curettage, contouring or resection may be indicated for
      functional or aesthetic reasons. Surgical procedures are usually performed when
      the disease becomes quiescent. Aggressive lesions that cause severe functional
      problems such as airway obstruction justify early surgical intervention.

PMID- 22640404
TI  - Edible coatings enriched with essential oils and their compounds for fresh and
      fresh-cut fruit.
AB  - Fresh fruit and vegetables consumption has increased in the past few years due to
      the enhanced awareness of consumers for healthy food. However, these products are
      highly perishable, and losses can be of great significance if postharvest correct
      management is not provided. Fresh-cut products are of increasing importance,
      since they are presented to the consumer in a state that allows for direct and
      immediate consumption. However, those products are even more perishable since
      cutting can induce a series of senescence associated responses to wounding, and
      are more susceptible to microbial spoilage. Edible coatings, which intend to
      reduce ripening processes and protect the fruit from water loss and spoilage may
      be a good way to enhance the shelf life of these products. More recently, the
      inclusion of additives into these edible coatings to increase their
      effectiveness, such as essential oils and their constituents with antimicrobial
      and antioxidant activities, has been reported and patented.

PMID- 22640405
TI  - Increased levels of circulating endothelial progenitor cells in patients with
      ischaemic stroke treated with statins during acute phase.
AB  - BACKGROUND AND PURPOSE: Endothelial progenitor cells (EPCs) have been suggested
      to be a therapeutic option in ischaemic stroke. Our aim was to study whether
      statin treatment during acute phase could increase circulating EPCs after acute
      ischaemic stroke. METHODS: We studied 48 patients with a first-ever non-lacunar
      ischaemic stroke (<12 h from stroke onset). Sixteen patients received statin
      treatment (20 mg atorvastatin/day) during the first 4 days. We defined the EPC
      increment during the first week as the difference in the number of early
      outgrowth colony-forming unit-endothelial cell (CFU-EC) between day 7 and at
      admission (previous to atorvastatin treatment). Serum levels of vascular
      endothelial growth factor and active matrix metalloproteinase 9 (determined by
      ELISA), and nitric oxide metabolites (NOx) (determined by high-performance liquid
      chromatography) were measured at admission, 24 and 72 h, and day 7. RESULTS:
      Colony-forming unit-endothelial cells were similar at baseline between patients
      treated (n = 16) and non-treated (n = 32) with statins (10.1 +/- 3.9 vs. 7.9 +/-
      6.9 CFU-EC, P = 0.223). However, patients treated with statins showed a higher
      EPC increment (24.0 +/- 17.3 vs. 6.0 +/- 17.8 CFU-EC, P = 0.002) during the first
      week. An EPC increment >= 4 CFU-EC predicted with the highest sensitivity (88%)
      and specificity (92%) the probability of good outcome (area under the curve
      0.903, P < 0.0001). Statin treatment (OR, 13.1; CI 95%, 2.2-76.9, P = 0.004) was
      independently associated with an EPC increment >= 4 CFU-EC after adjustment for
      confounder factors, but this association was lost when adjusting for NOx levels.
      CONCLUSIONS: Statin treatment for 4 days may increase circulating EPC levels,
      probably by NO-related mechanisms.

PMID- 22640406
TI  - Measuring workload for tuberculosis service provision at primary care level: a
      methodology.
AB  - We developed and piloted a methodology to establish TB related work load at
      primary care level for clinical and laboratory staff. Workload is influenced by
      activities to be implemented, time to perform them, their frequency and patient
      load. Of particular importance is the patient pathway for diagnosis and treatment
      and the frequency of clinic visits. Using observation with checklists, clocking,
      interviews and review of registers, allows assessing the contribution of
      different factors on the workload.

PMID- 22640407
TI  - H3K4me3 inversely correlates with DNA methylation at a large class of non-CpG
      island-containing start sites.
AB  - BACKGROUND: In addition to mutations, epigenetic silencing of genes has been
      recognized as a fundamental mechanism that promotes human carcinogenesis. To
      date, characterization of epigenetic gene silencing has largely focused on genes
      in which silencing is mediated by hypermethylation of promoter-associated CpG
      islands, associated with loss of the H3K4me3 chromatin mark. Far less is known
      about promoters lacking CpG-islands or genes that are repressed by alternative
      mechanisms. METHODS: We performed integrative ChIP-chip, DNase-seq, and global
      gene expression analyses in colon cancer cells and normal colon mucosa to
      characterize chromatin features of both CpG-rich and CpG-poor promoters of genes
      that undergo silencing in colon cancer. RESULTS: Epigenetically repressed genes
      in colon cancer separate into two classes based on retention or loss of H3K4me3
      at transcription start sites. Quantitatively, of transcriptionally repressed
      genes that lose H3K4me3 in colon cancer (K4-dependent genes), a large fraction
      actually lacks CpG islands. Nonetheless, similar to CpG-island containing genes,
      cytosines located near the start sites of K4-dependent genes become DNA
      hypermethylated, and repressed K4-dependent genes can be reactivated with 5
      azacytidine. Moreover, we also show that when the H3K4me3 mark is retained,
      silencing of CpG island-associated genes can proceed through an alternative
      mechanism in which repressive chromatin marks are recruited. CONCLUSIONS: H3K4me3
      equally protects from DNA methylation at both CpG-island and non-CpG island start
      sites in colon cancer. Moreover, the results suggest that CpG-rich genes
      repressed by loss of H3K4me3 and DNA methylation represent special instances of a
      more general epigenetic mechanism of gene silencing, one in which gene silencing
      is mediated by loss of H3K4me3 and methylation of non-CpG island promoter
      associated cytosines.

PMID- 22640408
TI  - XVth QTLMAS: simulated dataset.
AB  - BACKGROUND: Our aim was to simulate the data for the QTLMAS2011 workshop
      following a pig-type family structure under an oligogenic model, each QTL being
      specific. RESULTS: The population comprised 3000 individuals issued from 20 sires
      and 200 dams. Within each family, 10 progenies belonged to the experimental
      population and were assigned phenotypes and marker genotypes and 5 belonged to
      the selection population, only known on their marker genotypes. A total of 10,000
      SNPs carried by 5 chromosomes of 1 Morgan each were simulated. Eight QTL were
      created (1 quadri-allelic, 2 linked in phase, 2 linked in repulsion, 1 imprinted
      and 2 epistatic). Random noise was added giving an heritability of 0.30. The
      marker density, LD and MAF were similar to real life parameters.

PMID- 22640409
TI  - Italian chapter of the International Society of cardiovascular ultrasound expert
      consensus document on training requirements for noncardiologists using hand
      carried ultrasound devices.
AB  - Hand-carried ultrasound devices (HCDs), also named personal use echo, are pocket
      size, compact, and battery-equipped echocardiographic systems. They have limited
      technical capabilities but offer some advantages compared with standard
      echocardiographic devices due to their simplicity of use, immediate availability
      at the patient's bedside, transportability, and relatively low cost. Current HCDs
      are considered as screening tools and are used to complement the physical
      examination by cardiologists. Many noncardiologic subspecialists, however, have
      adopted this technologic advancement rapidly raising the concern of an
      inappropriate use of HCD by health professionals who do not have any specific
      training. In keeping with the mission of the International Society of
      Cardiovascular Ultrasound to advance the science and art of cardiovascular
      ultrasound and encourage the knowledge of this subject, the purpose of this
      Expert Consensus document is to focus on the training for all health care
      professionals considering the use of HCD. Accordingly, this paper summarizes
      general aspects of HCD, such as technical characteristics and clinical
      indications, and then details the specific training requirements for
      noncardiologists (i.e., training program, minimum case load, duration, and
      certification of competence).

PMID- 22640410
TI  - Bacterial succession during curing process of a skate (Dipturus batis) and
      isolation of novel strains.
AB  - AIMS: To study the succession of cultivated and uncultivated microbes during the
      traditional curing process of skate. METHODS AND RESULTS: The microbial diversity
      was evaluated by sequencing 16Sr RNA clone libraries and cultivation in variety
      of media from skate samples taken periodically during a 9-day curing process. A
      pH shift was observed (pH 6.64-9.27) with increasing trimethylamine (2.6 up to
      75.6 mg N per 100 g) and total volatile nitrogen (TVN) (from 58.5 to 705.8 mg N
      per 100 g) but with relatively slow bacterial growth. Uncured skate was dominated
      by Oceanisphaera and Pseudoalteromonas genera but was substituted after curing by
      Photobacterium and Aliivibrio in the flesh and Pseudomonas on the skin. Almost
      50% of the clone library is derived from putative undiscovered species.
      Cultivation and enrichment strategies resulted in isolation of putatively new
      species belonging to the genera Idiomarina, Rheinheimera, Oceanisphaera,
      Providencia and Pseudomonas. The most abundant genera able to hydrolyse urea to
      ammonia were Oceanisphaera, Psychrobacter, Pseudoalteromonas and isolates within
      the Pseudomonas genus. CONCLUSIONS: The curing process of skate is controlled and
      achieved by a dynamic bacterial community where the key players belong to
      Oceanisphaera, Pseudoalteromonas, Photobacterium, Aliivibrio and Pseudomonas.
      SIGNIFICANCE AND IMPACT OF THE STUDY: For the first time, the bacterial
      population developments in the curing process of skate are presented and
      demonstrate a reservoir of many yet undiscovered bacterial species.

PMID- 22640411
TI  - Variation in cancer surgical outcomes associated with physician and nurse
      staffing: a retrospective observational study using the Japanese Diagnosis
      Procedure Combination Database.
AB  - BACKGROUND: Little is known about the effects of professional staffing on cancer
      surgical outcomes. The present study aimed to investigate the association between
      cancer surgical outcomes and physician/nurse staffing in relation to hospital
      volume. METHODS: We analyzed 131,394 patients undergoing lung lobectomy,
      esophagectomy, gastrectomy, colorectal surgery, hepatectomy or pancreatectomy for
      cancer between July and December, 2007-2008, using the Japanese Diagnosis
      Procedure Combination database linked to the Survey of Medical Institutions data.
      Physician-to-bed ratio (PBR) and nurse-to-bed ratio (NBR) were determined for
      each hospital. Hospital volume was categorized into low, medium and high for each
      of six cancer surgeries. Failure to rescue (FTR) was defined as a proportion of
      inhospital deaths among those with postoperative complications. Multi-level
      logistic regression analysis was performed to examine the association between
      physician/nurse staffing and FTR, adjusting for patient characteristics and
      hospital volume. RESULTS: Overall inhospital mortality was 1.8%, postoperative
      complication rate was 15.2%, and FTR rate was 11.9%. After adjustment for
      hospital volume, FTR rate in the group with high PBR (>=19.7 physicians per 100
      beds) and high NBR (>=77.0 nurses per 100 beds) was significantly lower than that
      in the group with low PBR (<19.7) and low NBR (<77.0) (9.2% vs. 14.5%; odds
      ratio, 0.76; 95% confidence interval, 0.68-0.86; p < 0.001). CONCLUSIONS: Well
      staffed hospitals confer a benefit for cancer surgical patients regarding reduced
      FTR, irrespective of hospital volume. These results suggest that consolidation of
      surgical centers linked with migration of medical professionals may improve the
      quality of cancer surgical management.

PMID- 22640412
TI  - Isolated bifid rib: clinical and radiological findings in children.
AB  - BACKGROUND: Bifid rib is usually asymptomatic but sometimes occurs associated
      with other pathological conditions. The aim of this study was to investigate
      clinical and radiological characteristics in children with bifid rib. METHODS:
      Nine children with the diagnosis of bifid rib between 2005 and 2010 were
      reviewed. Chest radiography and computed tomography (CT) were performed in all
      patients, and 3-D images were additionally reconstructed in six patients.
      RESULTS: Five girls and four boys with a mean age at presentation of 4.2 years
      had various types of unilateral bifid rib. Seven patients complained of a chest
      wall mass, whereas two patients whose costal abnormalities were incidentally
      detected on chest radiography were asymptomatic. Bifid ribs were confirmed on
      plain radiographs in six patients, while the other three patients were finally
      diagnosed on reconstruction 3D-CT. One patient with a flared rib on a radiograph
      showed bifurcation of the costal cartilage on 3D-CT. The other two patients with
      upper rib abnormalities on radiography had downward extension of the cervical or
      first rib articulating with the upper branch of the bifid first or second rib,
      respectively. CONCLUSION: Reconstruction 3D-CT can demonstrate complicated
      thoracic abnormalities in patients with atypical appearance of the rib on plain
      radiographs. An isolated bifid rib may require no further intervention.

PMID- 22640413
TI  - Utility of hemoglobin A1c for the identification of individuals with diabetes and
      prediabetes in a Chinese high risk population.
AB  - BACKGROUND: The aim of the study was to assess the utility of Hemoglobin A1c
      (HbA1c) to identify individuals with undiagnosed DM and prediabetes (preDM) in
      the high risk population of Chinese people. METHODS: A total of 424 high risk
      individuals without known diabetes, who met at least three of the high risk
      factors for DM (hypertension, abnormal blood lipid, family history of DM and high
      BMI) were selected for this study, HbA1c, fasting plasma concentrations of
      glucose (FPG) and a 75 g oral glucose tolerance test (OGTT) were measured. The
      performance of HbA1c in relation to undiagnosed DM and preDM investigated through
      receiver operating characteristic (ROC) curves, the reference for DM and preDM,
      are according to the 2011 WHO-FPG/OGTT criteria and the appropriate cut-off
      points of HbA1c for DM and preDM were assessed. The properties of HbA1c
      diagnosing DM and preDM were also compared with that of the fasting plasma
      glucose (FPG). RESULTS: It was shown that the AUC (area under the curve) of the
      ROC curve for HbA1c predicting undiagnosed DM was similar to that of FPG, and the
      cut-off point of HbA1c 6.2% was optimal for predicting DM, with a sensitivity of
      66%, and a specificity of 91%. Furthermore, the cut-off point of HbA1c was 5.9%
      for preDM with a sensitivity of 70%, a specificity of 87%. CONCLUSION:
      Collectively, this study found that the measurement of HbA1c may be efficient to
      diagnosis undiagnosed both DM and preDM with the cut-off point of 6.2% and 5.9%,
      respectively.

PMID- 22640414
TI  - Self-concept in youth with congenital facial differences: development and
      recommendations for medical providers.
AB  - Congenital facial differences may impact a child's self-perception, activities
      and valuation, and what has been termed their "self-concept." This article
      reviews what constitutes self-concept, and its development during childhood and
      adolescence. The literature examining the role of physical appearance,
      specifically congenital facial differences on individuals' perceptions of self
      are reviewed in the context of psychosocial development. Positive self-concept
      can impact healthy behaviors, positive interactions with peers, and academic
      achievement. The role of mental health professionals in evaluating self-concept
      and objective measures of self-concept are discussed, and recommendations are
      made to assist medical practitioners regarding monitoring and encouragement of
      positive self-concept in children with congenital facial differences.

PMID- 22640415
TI  - A shot in the genome: how accurately do shotgun 454 sequences represent a genome?
AB  - BACKGROUND: Next generation sequencing (NGS) provides a valuable method to
      quickly obtain sequence information from non-model organisms at a genomic scale.
      In principle, if sequencing is not targeted for a genomic region or sequence type
      (e.g. coding region, microsatellites) NGS reads can be used as a genome snapshot
      and provide information on the different types of sequences in the genome.
      However, no study has ascertained if a typical 454 dataset of low coverage (1/4
      1/8 of a PicoTiter plate leading to generally less than 0.1x of coverage)
      represents all parts of genomes equally. FINDINGS: Partial genome shotgun
      sequencing of total DNA (without enrichment) on a 454 NGS platform was used to
      obtain reads of Apis mellifera (454 reads hereafter). These 454 reads were
      compared to the assembled chromosomes of this species in three different aspects:
      (i) dimer and trimer compositions, (ii) the distribution of mapped 454 sequences
      along the chromosomes and (iii) the numbers of different classes of
      microsatellites. Highly significant chi-square tests for all three types of
      analyses indicated that the 454 data is not a perfect random sample of the
      genome. Only the number of 454 reads mapped to each of the 16 chromosomes and the
      number of microsatellites pooled by motif (repeat unit) length was not
      significantly different from the expected values. However, a very strong
      correlation (correlation coefficients greater than 0.97) was observed between
      most of the 454 variables (the number of different dimers and trimers, the number
      of 454 reads mapped to each chromosome fragments of one Mb, the number of 454
      reads mapped to each chromosome, the number of microsatellites of each class) and
      their corresponding genomic variables. CONCLUSIONS: The results of chi square
      tests suggest that 454 shotgun reads cannot be regarded as a perfect
      representation of the genome especially if the comparison is done on a finer
      scale (e.g. chromosome fragments instead of whole chromosomes). However, the high
      correlation between 454 and genome variables tested indicate that a high
      proportion of the variability of 454 variables is explained by their genomic
      counterparts. Therefore, we conclude that using 454 data to obtain information on
      the genome is biologically meaningful.

PMID- 22640416
TI  - The variable N-terminal region of DDX5 contains structural elements and auto
      inhibits its interaction with NS5B of hepatitis C virus.
AB  - RNA helicases of the DEAD (Asp-Glu-Ala-Asp)-box family of proteins are involved
      in many aspects of RNA metabolism from transcription to RNA decay, but most of
      them have also been shown to be multifunctional. The DEAD-box helicase DDX5 of
      host cells has been shown to interact with the RNA-dependent RNA polymerase
      (NS5B) of HCV (hepatitis C virus). In the present study, we report the presence
      of two independent NS5B-binding sites in DDX5, one located at the N-terminus and
      another at the C-terminus. The N-terminal fragment of DDX5, which consists of the
      first 305 amino acids and shall be referred as DDX5-N, was expressed and
      crystallized. The crystal structure shows that domain 1 (residues 79-303) of DDX5
      contains the typical features found in the structures of other DEAD-box
      helicases. DDX5-N also contains the highly variable NTR (N-terminal region) of
      unknown function and the crystal structure reveals structural elements in part of
      the NTR, namely residues 52-78. This region forms an extensive loop and an alpha
      helix. From co-immunoprecipitation experiments, the NTR of DDX5-N was observed to
      auto-inhibit its interaction with NS5B. Interestingly, the alpha-helix in NTR is
      essential for this auto-inhibition and seems to mediate the interaction between
      the highly flexible 1-51 residues in NTR and the NS5B-binding site in DDX5-N.
      Furthermore, NMR investigations reveal that there is a direct interaction between
      DDX5 and NS5B in vitro.

PMID- 22640417
TI  - Using verification feedback to correct errors made on a multiple-choice test.
AB  - A key educational challenge is how to correct students' errors and misconceptions
      so that they do not persist. Simply labelling an answer as correct or incorrect
      on a short-answer test (verification feedback) does not improve performance on
      later tests; error correction requires receiving answer feedback. We explored the
      generality of this conclusion and whether the effectiveness of verification
      feedback depends on the type of test with which it is paired. We argue that,
      unlike for short-answer tests, learning whether one's multiple-choice selection
      is correct or incorrect should help participants narrow down the possible answers
      and identify specific lures as false. To test this proposition we asked
      participants to answer a series of general knowledge multiple-choice questions.
      They received no feedback, answer feedback, or verification feedback, and then
      took a short-answer test immediately and two days later. Verification feedback
      was just as effective as answer feedback for maintaining correct answers.
      Importantly, verification feedback allowed learners to correct more of their
      errors than did no feedback, although it was not as effective as answer feedback.
      Overall, verification feedback conveyed information to the learner, which has
      both practical and theoretical implications.

PMID- 22640418
TI  - Current treatment protocols can offer a normal or near-normal quality of life in
      the majority of patients with non-functioning pituitary adenomas.
AB  - OBJECTIVE: Non-functioning pituitary adenomas (NFA) may be associated with
      significant morbidity. Published data on the quality of life (QoL) of patients
      with NFA are scarce and conflicting. In view of the discordant findings and the
      advances in the management of these subjects, we aimed to evaluate the QoL in
      patients with NFA followed up in a tertiary endocrine UK referral centre.
      SUBJECTS AND METHODS: All consecutive patients with NFA attending the outpatient
      clinic in the Department of Endocrinology in Oxford over a 6-month period (n =
      193) were offered 3 health-related QoL questionnaires [Short Form 36 (SF36),
      Nottingham Health Profile (NHP), European Quality of Life Scale (EuroQoL)] to
      complete. Patient outcomes (response rate 93.3%) were compared with age-related
      UK reference values. RESULTS: None of the QoL scores in the SF-36 or the 5
      dimensions of health in the EuroQoL was different from the reference values. The
      visual analogue scale (VAS) score (EuroQoL) was slightly compromised (P = 0.041).
      In the NHP questionnaire, males had no parameter significantly affected, whereas
      females performed worse in 1/6 areas (energy levels). Tumour recurrence was an
      independent predictor for compromised VAS score and for anxiety/depression
      (EuroQoL), and visual field defects for more frequent problems with
      interests/hobbies (NHP). CONCLUSIONS: Overall, the health-related QoL and
      perception of subjective health in patients with NFA was not compromised to any
      major extent suggesting that we can now offer the prospect of treatment and
      replacement, which will provide a normal or near-normal QoL. Specific groups are
      affected in various dimensions, necessitating measures to compensate for
      predisposing factors.

PMID- 22640419
TI  - Preclinical students' experiences in early clerkships after skills training
      partly offered in primary health care centers: a qualitative study from
      Indonesia.
AB  - BACKGROUND: Students may encounter difficulties when they have to apply clinical
      skills trained in their pre-clinical studies in clerkships. Early clinical
      exposure in the pre-clinical phase has been recommended to reduce these
      transition problems. The aim of this study is to explore differences in students'
      experiences during the first clerkships between students exclusively trained in a
      skills laboratory and peers for whom part of their skills training was
      substituted by early clinical experiences (ECE). METHODS: Thirty pre-clinical
      students trained clinical skills exclusively in a skills laboratory; 30 peers
      received part of their skills training in PHC centers. Within half a year after
      commencing their clerkships all 60 students shared their experiences in focus
      group discussions (FGDs). Verbatim transcripts of FGDs were analyzed using Atlas
      Ti software. RESULTS: Clerkship students who had participated in ECE in PHC
      centers felt better prepared to perform their clinical skills during the first
      clerkships than peers who had only practiced in a skills laboratory. ECE in PHC
      centers impacted positively in particular on students' confidence, clinical
      reasoning, and interpersonal communication. CONCLUSION: In the Indonesian setting
      ECE in PHC centers reduce difficulties commonly encountered by medical students
      in the first clerkships.

PMID- 22640420
TI  - Consensus: a framework for evaluation of uncertain gene variants in laboratory
      test reporting.
AB  - Accurate interpretation of gene testing is a key component in customizing patient
      therapy. Where confirming evidence for a gene variant is lacking, computational
      prediction may be employed. A standardized framework, however, does not yet exist
      for quantitative evaluation of disease association for uncertain or novel gene
      variants in an objective manner. Here, complementary predictors for missense gene
      variants were incorporated into a weighted Consensus framework that includes
      calculated reference intervals from known disease outcomes. Data visualization
      for clinical reporting is also discussed.

PMID- 22640421
TI  - Survey of co-infection by Salmonella and oxyurids in tortoises.
AB  - BACKGROUND: Salmonella spp. and oxyurids are among the most prevalent bacterial
      and parasitic agents in reptiles. These organisms are routinely isolated in
      healthy tortoises, although heavy infections may cause significant pathology.
      Tortoises are considered a common source of reptile-associated salmonellosis, an
      important zoonosis reported worldwide. A survey of the prevalence of Salmonella
      spp. and oxyurids in 53 tortoises was conducted in southern Italy and a possible
      correlation between the two pathogens was therefore investigated. RESULTS:
      Salmonella spp. and oxyurids were detected with a prevalence of 49.1 and 81.1%,
      respectively. A significant positive correlation between Salmonella spp. and
      oxyurids was demonstrated. However, confounding factors related to husbandry
      could have been involved in determining this correlation. CONCLUSIONS: Our
      results suggest that caution should be exercised in translocation, husbandry, and
      human contact with tortoises and other exotic pets. Further studies on the
      epidemiology, molecular characterization and pathogenesis of Salmonella and
      oxyurids are needed to assess the actual impact of these organisms, as single or
      associated infections, on tortoises and on other exotic pets.

PMID- 22640422
TI  - Metabolic programming of sirtuin 1 (SIRT1) expression by moderate energy
      restriction during gestation in rats may be related to obesity susceptibility in
      later life.
AB  - In rats, 20% gestational energy restriction programmes offspring for higher food
      intake, which in adulthood results in higher body weight in males but not in
      females. Here, we aimed to assess whether the effects of moderate energy
      restriction during gestation and the sex-related outcomes on adult body weight
      may be related to the metabolic programming of sirtuin expression in different
      tissues. For this purpose, 25-d-old offspring of control and 20% energy
      restricted (ER) rats (from days 1-12 of pregnancy) were studied. Body weight and
      the weight of white adipose tissue (WAT) depots and liver were recorded and mRNA
      expression of sirtuin 1 (SIRT1) and selected genes in the WAT, liver, muscle and
      hypothalamus were analysed. No differences were found in body weight or the
      weight of WAT and liver between the control and ER animals. A similar pattern of
      SIRT1 mRNA expression was found in the WAT, liver and skeletal muscle of ER
      animals, but in a sex-dependent manner: ER males showed lower SIRT1 mRNA levels
      than the controls, while no differences were found in females. A sex-different
      pattern was also observed in the hypothalamus. ER males, but not females, also
      showed lower mRNA levels of adipose TAG lipase (ATGL) and uncoupling protein 2 in
      WAT and of sterol response element binding protein 1c and stearoyl-CoA desaturase
      1 in the liver. Both sexes of ER animals showed lower mRNA levels of 5' adenosine
      monophosphate-activated protein kinase and ATGL in the liver. In conclusion,
      moderate maternal energy restriction during gestation programmes a particular,
      sex-dependent gene expression profile of SIRT1 in different peripheral tissues,
      which may be related to obesity predisposition in adulthood; therefore SIRT1
      expression emerges as a potential early biomarker of obesity susceptibility.

PMID- 22640424
TI  - Many of the advancements in dermatologic surgery have come within the past
      decade. Introduction.

PMID- 22640425
TI  - Key moments in the history of dermatologic surgery (1952-2000).
AB  - The history of surgery in dermatology ("dermatologic surgery") is rich with
      significant developments and advances by multiple individuals. Only a few of
      these pioneers can be highlighted in this report because of space limitations. My
      apologies to colleagues and friends who have not been included or mentioned in
      this article. The Timeline: Major milestones in the history of dermatologic
      surgery in this article tells some of the story. The biographic pieces on 15
      outstanding physicians add additional detail and perspective. Many major
      developments have occurred since 2000, but they are beyond the scope of this
      article.

PMID- 22640423
TI  - Absence of amyloid beta oligomers at the postsynapse and regulated synaptic Zn2+
      in cognitively intact aged individuals with Alzheimer's disease neuropathology.
AB  - BACKGROUND: Early cognitive impairment in Alzheimer Disease (AD) is thought to
      result from the dysfunctional effect of amyloid beta (Abeta) oligomers targeting
      the synapses. Some individuals, however, escape cognitive decline despite the
      presence of the neuropathologic features of AD (Abeta plaques and neurofibrillary
      tangles). We term this group Non-Demented with AD Neuropathology or NDAN. The
      present study illustrates one putative resistance mechanism involved in NDAN
      cases which may suggest targets for the effective treatment of AD. RESULTS: Here
      we describe the localization of Abeta oligomers at the postsynapse in hippocampi
      from AD cases. Notably, however, we also found that while present in soluble
      fractions, Abeta oligomers are absent from hippocampal postsynapses in NDAN
      cases. In addition, levels of phosphorylated (active) CREB, a transcription
      factor important for synaptic plasticity, are normal in NDAN individuals,
      suggesting that their synapses are functionally intact. Analysis of Zn2+ showed
      that levels were increased in both soluble fractions and synaptic vesicles in AD
      hippocampi, paralleled by a decrease of expression of the synaptic vesicle Zn2+
      transporter, ZnT3. Conversely, in NDAN individuals, levels of Zn2+ in soluble
      fractions were significantly lower than in AD, whereas in synaptic vesicles the
      levels of Zn2+ were similar to AD, but accompanied by preserved expression of the
      ZnT3. CONCLUSIONS: Taken together, these data illustrate that despite substantial
      AD neuropathology, Abeta oligomers, and increased synaptic vesicle Zn2+,
      susceptible brain tissue in these aged NDAN individuals features, as compared to
      symptomatic AD subjects, significantly lower total Zn2+ levels and no association
      of Abeta oligomers with the postsynapse, which collectively may promote the
      maintenance of intact cognitive function.

PMID- 22640426
TI  - The Stegman Papers: biography of a leader in dermatologic surgery.
AB  - The Stegman Papers is a biography of Dr. Samuel J. Stegman. The papers were
      collected by Dr. Stegman during his lifetime as a dermatologic surgeon and
      leader. The manuscript includes a time line of Dr. Stegman's life and listing of
      his accomplishments, including significant publications.

PMID- 22640427
TI  - Fillers: from the past to the future.
AB  - Modern medical use of injectable soft-tissue augmentation fillers has evolved
      from the introduction of bovine collage implants to an array of synthesized
      materials in the current domestic and foreign markets. The concept of
      augmentation has moved from simple lines, scars, and wrinkles to revolumizing the
      aging face. A brief overview of the past, present, and future injectable fillers
      is presented.

PMID- 22640428
TI  - New frontiers in laser surgery.
AB  - The simultaneous advances in engineering, medicine, and molecular biology have
      accelerated the pace of introductions of new light-based technologies in
      dermatology. In this review, the authors examine recent advances in laser surgery
      as well as peer into the future of energy-based cutaneous medicine. The future
      landscape of dermatology will almost undoubtedly include (1) noninvasive imaging
      technologies and (2) improved "destructive" modalities based on real-time
      feedback from the skin surface.

PMID- 22640430
TI  - Fractionation: past, present, future.
AB  - The development of fractional photothermolysis is a milestone in the history of
      laser technology and cutaneous resurfacing. Based on the concept that skin is
      treated in a fractional manner, where narrow cylinders of tissue are thermally
      heated and normal adjacent skin is left unaffected, the fractional devices have
      shown effectiveness in treating a variety of conditions. Since its development,
      we are becoming more adept at using optimal parameters to induce near carbon
      dioxide laser benefits with a much more comfortable postoperative period and
      fewer complications. The future remains bright for fractionated laser devices and
      with new devices and wavelengths, the applications of this technology continue to
      grow.

PMID- 22640429
TI  - The horizon for treating cutaneous vascular lesions.
AB  - Dermatologists encounter a wide range of cutaneous vascular lesions, including
      infantile hemangiomas, port-wine stain birthmarks, arteriovenous malformations,
      venous malformations, Kaposi sarcomas, angiosarcomas, and angiofibromas. Current
      treatment modalities to reduce these lesions include topical and/or intralesional
      steroids, laser therapy, surgical resection, and endovascular therapy. However,
      each method has limitations owing to recurrence, comorbidities, toxicity, or
      lesion location. Photodynamic therapy, antiangiogenic therapy, and evolving
      methods of sclerotherapy are promising areas of development that may mitigate
      limitations of current treatments and offer exciting options for patients and
      their physicians.

PMID- 22640432
TI  - Body contouring: the skinny on noninvasive fat removal.
AB  - Historically, the approach to body contouring has largely involved invasive
      procedures, such as liposuction. Recently, several new devices for noninvasive
      fat removal have received clearance by the Food and Drug Administration for the
      treatment of focal adiposity. Modalities are aimed primarily at targeting the
      physical properties of fat that differentiate it from the overlying epidermis and
      dermis, thus selectively resulting in removal. This review will focus on 3 novel
      approaches to noninvasive selective destruction of fat.

PMID- 22640431
TI  - Ablative fractional resurfacing for the treatment of traumatic scars and
      contractures.
AB  - After a decade of military conflict, thousands of wounded warriors have suffered
      debilitating and cosmetically disfiguring scars and scar contractures. Clearly,
      there is a need for effective scar treatment regimens to assist in the functional
      and cosmetic rehabilitation of these patients. Traditional treatments, including
      aggressive physical and occupational therapy and dedicated wound care, are
      essential. Adjunctive treatments with established laser technologies, such as
      vascular lasers and full-field ablative lasers, have had a somewhat limited role
      in scar contractures due to modest efficacy and/or an unacceptable side effect
      profile in compromised skin. Refractory scar contractures often require surgical
      revision, which can be effective, but is associated with additional surgical
      morbidity and a significant risk of recurrence. Furthermore, current scar
      treatment paradigms often dictate scar maturation for approximately a year to
      allow for spontaneous improvement before surgical intervention. Since 2009, the
      Dermatology Clinic at the Naval Medical Center San Diego has been treating scars
      and scar contractures in wounded warriors and others using ablative fractionated
      laser technology. Although traditionally associated with the rejuvenation of aged
      and photo-damaged skin, our clinical experience and a handful of early reports
      indicate that laser ablative fractional resurfacing demonstrates promising
      efficacy and an excellent side effect profile when applied to the functional and
      cosmetic enhancement of traumatic scars and contractures. This article discusses
      our clinical experience with ablative fractional resurfacing and its potential
      prominent role in rehabilitation from traumatic injuries, including a possible
      shift in scar treatment paradigms toward earlier procedural intervention.
      Potential benefits include the optimization of scar trajectory and higher levels
      of full or adapted function in a more favorable time course.

PMID- 22640433
TI  - The evolution of melasma therapy: targeting melanosomes using low-fluence Q
      switched neodymium-doped yttrium aluminium garnet lasers.
AB  - Melasma is an acquired disorder of pigmentation that commonly affects women with
      phototypes III-V, and it has a negative impact on the quality of life in affected
      individuals. It presents clinically as symmetric tan or brown patches on the
      face, most often involving the forehead, cheeks, perioral region, and periorbital
      region. On histologic examination, there is increased melanin in the epidermis
      and/or an increased number of melanosomes in the dermis, with a normal number of
      highly melanized and dendritic melanocytes. The mainstay of treatment is the use
      of sunscreen along with topical medications that suppress melanogenesis.
      Clearance is usually incomplete and recurrences or exacerbations are frequent,
      probably because of the poor efficacy in clearing dermal melanosomes. Treatment
      with high-energy pigment-specific lasers, ablative resurfacing lasers, and
      fractional lasers results in an unacceptably high rate of postinflammatory hyper-
      and hypopigmentation and rebound melasma. Recently, promising results have been
      achieved with low-fluence Q-switched neodymium-doped yttrium aluminium garnet
      laser treatment, which can selectively target dermal melanosomes without
      producing inflammation or epidermal damage, in all skin phototypes. This article
      reviews the current treatment modalities for melasma, the rationale for using and
      the clinical results of combination therapy with low-fluence Q-switched neodymium
      doped yttrium aluminium garnet lasers.

PMID- 22640434
TI  - New horizons in treating disorders of hyperpigmentation in skin of color.
AB  - Pigmentary abnormalities are among the most common reasons why patients with skin
      of color visit a dermatologist. Hydroquinone has been a cornerstone for the
      treatment of hyperpigmentation; however, concerns regarding adverse effects have
      prompted a search for alternative agents. Some promising topical treatments
      include soy, licorice, rucinol, mulberry, niacinamide, ellagic acid, resveratrol,
      and dioic acid. Oral agents, primarily used for the prevention of postprocedural
      hyperpigmentation, include procyanidins, tranexamic acid, and Polypodium
      leucotomos. Advances in Q-switched lasers, intense pulse light, fractional
      photothermolysis, and the advent of tretinoin peeling add to the clinician's
      armamentarium for treating hyperpigmentation.

PMID- 22640436
TI  - Genomic selection using regularized linear regression models: ridge regression,
      lasso, elastic net and their extensions.
AB  - BACKGROUND: Genomic selection (GS) is emerging as an efficient and cost-effective
      method for estimating breeding values using molecular markers distributed over
      the entire genome. In essence, it involves estimating the simultaneous effects of
      all genes or chromosomal segments and combining the estimates to predict the
      total genomic breeding value (GEBV). Accurate prediction of GEBVs is a central
      and recurring challenge in plant and animal breeding. The existence of a
      bewildering array of approaches for predicting breeding values using markers
      underscores the importance of identifying approaches able to efficiently and
      accurately predict breeding values. Here, we comparatively evaluate the
      predictive performance of six regularized linear regression methods-- ridge
      regression, ridge regression BLUP, lasso, adaptive lasso, elastic net and
      adaptive elastic net-- for predicting GEBV using dense SNP markers. METHODS: We
      predicted GEBVs for a quantitative trait using a dataset on 3000 progenies of 20
      sires and 200 dams and an accompanying genome consisting of five chromosomes with
      9990 biallelic SNP-marker loci simulated for the QTL-MAS 2011 workshop. We
      applied all the six methods that use penalty-based (regularization) shrinkage to
      handle datasets with far more predictors than observations. The lasso, elastic
      net and their adaptive extensions further possess the desirable property that
      they simultaneously select relevant predictive markers and optimally estimate
      their effects. The regression models were trained with a subset of 2000
      phenotyped and genotyped individuals and used to predict GEBVs for the remaining
      1000 progenies without phenotypes. Predictive accuracy was assessed using the
      root mean squared error, the Pearson correlation between predicted GEBVs and (1)
      the true genomic value (TGV), (2) the true breeding value (TBV) and (3) the
      simulated phenotypic values based on fivefold cross-validation (CV). RESULTS: The
      elastic net, lasso, adaptive lasso and the adaptive elastic net all had similar
      accuracies but outperformed ridge regression and ridge regression BLUP in terms
      of the Pearson correlation between predicted GEBVs and the true genomic value as
      well as the root mean squared error. The performance of RR-BLUP was also somewhat
      better than that of ridge regression. This pattern was replicated by the Pearson
      correlation between predicted GEBVs and the true breeding values (TBV) and the
      root mean squared error calculated with respect to TBV, except that accuracy was
      lower for all models, most especially for the adaptive elastic net. The
      correlation between the predicted GEBV and simulated phenotypic values based on
      the fivefold CV also revealed a similar pattern except that the adaptive elastic
      net had lower accuracy than both the ridge regression methods. CONCLUSIONS: All
      the six models had relatively high prediction accuracies for the simulated data
      set. Accuracy was higher for the lasso type methods than for ridge regression and
      ridge regression BLUP.

PMID- 22640435
TI  - Cutting edge in medical management of cutaneous oncology.
AB  - Traditional chemotherapy has resulted in only a modest response, if any, for the
      3 most common cutaneous malignancies of basal cell carcinoma, squamous cell
      carcinoma, and melanoma. Recent advances in understanding of the defects in the
      pathways driving tumorigenesis have changed the way that we think of these
      cancers and paved the way to targeted therapy for specific tumors. In this
      review, we will introduce the novel systemic treatments currently available for
      these cancers in the context of what is understood about the tumor pathogenesis.
      We will also introduce ongoing studies that will hopefully broaden our options
      for highly effective and tolerable treatment.

PMID- 22640437
TI  - Primary prevention of overweight in children and adolescents: a meta-analysis of
      the effectiveness of interventions aiming to decrease sedentary behaviour.
AB  - The objectives of this meta-analysis were to provide an overview of the evidence
      regarding the effects of interventions, implemented in the school- and general
      population setting, aiming to prevent excessive sedentary behaviour in children
      and adolescents on (1) the amount of sedentary behaviour and (2) BMI. Differences
      in effects on sedentary behaviour and BMI between single health behaviour
      interventions (sedentary behaviour only) and multiple health behaviour
      interventions were explored. A literature search was conducted in PubMed, EMBASE,
      Web of Science, PsycINFO and Cochrane Database of Systematic Reviews. Thirty-four
      (R)CT studies evaluating 33 general population interventions, published between
      1990 and April 2011, aiming to decrease sedentary behaviour in normal weight
      children or adolescents (0-18 years) were included. Intervention duration ranged
      from 7 days to 4 years. Mean change in sedentary behaviour and BMI from baseline
      to post-intervention was calculated using a random effects model. Results showed
      significant decreases for the amount of sedentary behaviour and BMI. For
      sedentary behaviour the post-intervention mean difference was -17.95 min/day
      (95%CI:-26.61;-9.28); the change-from-baseline mean difference was -20.44 min/day
      (95%CI:-30.69;-10.20). For BMI the post-intervention mean difference was -0.25
      kg/m2 (95%CI:-0.40;-0.09); the change-from-baseline mean difference was -0.14
      kg/m2 (95%CI:-0.23;-0.05). No differences were found between single and multiple
      health behaviour interventions. Interventions in the school- and general
      population setting aiming to reduce only sedentary behaviour and interventions
      targeting multiple health behaviours can result in significant decreases in
      sedentary behaviour. Studies need to increase follow-up time to estimate the
      sustainability of the intervention effects found.

PMID- 22640438
TI  - Placental size at 19 weeks predicts offspring bone mass at birth: findings from
      the Southampton Women's Survey.
AB  - OBJECTIVES: In this study we investigate the relationships between placental size
      and neonatal bone mass and body composition, in a population-based cohort. STUDY
      DESIGN: 914 mother-neonate pairs were included. Placental dimensions were
      measured via ultrasound at 19 weeks gestation. Dual X-ray absorptiometry (DXA)
      was performed on the neonates within the first two weeks of life. RESULTS: We
      observed positive relationships between placental volume at 19 weeks, and
      neonatal bone area (BA; r = 0.26, p < 0.001), bone mineral content (BMC; r =
      0.25, p < 0.001) and bone mineral density (BMD; r = 0.10, p = 0.001). Thus
      placental volume accounted for 6.25% and 1.2% of the variation in neonatal BMC
      and BMD respectively at birth. These associations remained after adjustment for
      maternal factors previously shown to be associated with neonatal bone mineral
      accrual (maternal height, smoking, walking speed in late pregnancy, serum 25(OH)
      vitamin D and triceps skinfold thickness). CONCLUSIONS: We found that placental
      volume at 19 weeks gestation was positively associated with neonatal bone size
      and mineral content. These relationships appeared independent of those maternal
      factors known to be associated with neonatal bone mass, consistent with notion
      that such maternal influences might act through modulation of aspects of
      placental function, e.g. utero-placental blood flow or maternal nutrient
      concentrations, rather than placental size itself. Low placental volume early in
      pregnancy may be a marker of a reduced postnatal skeletal size and increased risk
      of later fracture.

PMID- 22640439
TI  - The impact of decision aids to enhance shared decision making for diabetes (the
      DAD study): protocol of a cluster randomized trial.
AB  - BACKGROUND: Shared decision making contributes to high quality healthcare by
      promoting a patient-centered approach. Patient involvement in selecting the
      components of a diabetes medication program that best match the patient's values
      and preferences may also enhance medication adherence and improve outcomes.
      Decision aids are tools designed to involve patients in shared decision making,
      but their adoption in practice has been limited. In this study, we propose to
      obtain a preliminary estimate of the impact of patient decision aids vs. usual
      care on measures of patient involvement in decision making, diabetes care
      processes, medication adherence, glycemic and cardiovascular risk factor control,
      and resource utilization. In addition, we propose to identify, describe, and
      explain factors that promote or inhibit the routine embedding of decision aids in
      practice. METHODS/DESIGN: We will be conducting a mixed-methods study comprised
      of a cluster-randomized, practical, multicentered trial enrolling clinicians and
      their patients (n = 240) with type 2 diabetes from rural and suburban primary
      care practices (n = 8), with an embedded qualitative study to examine factors
      that influence the incorporation of decision aids into routine practice. The
      intervention will consist of the use of a decision aid (Statin Choice and Aspirin
      Choice, or Diabetes Medication Choice) during the clinical encounter. The
      qualitative study will include analysis of video recordings of clinical
      encounters and in-depth, semi-structured interviews with participating patients,
      clinicians, and clinic support staff, in both trial arms. DISCUSSION: Upon
      completion of this trial, we will have new knowledge about the effectiveness of
      diabetes decision aids in these practices. We will also better understand the
      factors that promote or inhibit the successful implementation and normalization
      of medication choice decision aids in the care of chronic patients in primary
      care practices. TRIAL REGISTRATION: NCT00388050.

PMID- 22640440
TI  - The Global Fund Round 11 cancellation fiasco: turning disaster into opportunity?

PMID- 22640441
TI  - Relative reproductive fitness of the W-Beijing genotype.

PMID- 22640442
TI  - Lack of evidence to support policy development for management of contacts of
      multidrug-resistant tuberculosis patients: two systematic reviews.
AB  - BACKGROUND: Existing international guidelines provide different recommendations
      for the management of contacts of multidrug-resistant tuberculosis (MDR-TB)
      patients. OBJECTIVE: To conduct two systematic reviews with the aim of
      identifying chemoprophylactic approaches that are effective  in contacts of MDR
      TB patients to assist in policy making. DESIGN: We systematically searched the
      Medline, Embase, Central, LILACS, TRIP and BIOSIS Preview databases for studies
      on the effectiveness of anti-tuberculosis drugs in preventing active TB in
      persons at risk of developing MDR-TB.  This was done as an update of a systematic
      review from 2006 using the same methodology. In addition, we searched for studies
      including persons at risk of developing TB after exposure to non-MDR-TB patients
      who were treated with anti-tuberculosis drugs other than isoniazid or rifampicin.
      RESULTS: Of 1195 references assessed in the update, one additional study could be
      included. As the initial review included two studies, the total number of
      included studies equals three. One study reported no contacts who developed TB,
      whether or not they received prophylaxis. The other two studies  showed non
      significant risk differences of 4% (95%CI -3 to 12), and 5% (95%CI -2 to 11),
      both in favour of chemoprophylaxis. For the additional review, 2480 references
      were assessed, but none could be included. CONCLUSION: The attention given to MDR
      TB in recent years has not  resulted in publications on preventive treatment for
      contacts of MDR-TB patients. The available evidence is not sufficient to support
      or reject preventive treatment. Furthermore, the combined available evidence is
      of very low quality.

PMID- 22640443
TI  - Recent transmission of W-Beijing family Mycobacterium tuberculosis in rural
      eastern China.
AB  - OBJECTIVE: To understand the degree of recent transmission of tuberculosis (TB)
      and determine the risk factors associated with recent transmission stratified by
      W-Beijing genotype in rural China. DESIGN: A cross-sectional study of
      bacteriologically confirmed TB patients registered  in two rural counties of
      eastern China over a 1-year period. RESULTS: Of 351 patient isolates,
      spoligotyping identified 243 (69.2%) as W-Beijing family strains, and 53 (15.1%)
      and 15 (4.3%) as members of T1 Family and Family 33, respectively. Insertion
      sequence (IS) 6110 based restriction  fragment length polymorphism typing
      revealed that 31 clusters together accounted for 80 of the 351 isolates. Strains
      with the W-Beijing genotype were more likely to be clustered than non-Beijing
      strains (42.3% vs. 8.3%, P < 0.001). The proportion of cases due to recent
      transmission  was estimated at 23.1% (32.1% W-Beijing genotype vs. 2.8% non-W
      Beijing genotype). Multivariate analysis showed that bacille Calmette-Guerin
      (BCG) vaccination (aOR 2.97), multidrug resistance (aOR 5.45) and body mass index
      (aOR 1.13) were independent predictors for clustering among  W-Beijing isolates.
      CONCLUSIONS: The low clustering proportions highlight the role of endogenous
      reactivation of TB as a main concern in rural eastern China. Our findings also
      suggest that W-Beijing strains were associated with recent transmission in this
      population, where multidrug resistance  and BCG vaccination may play an important
      role in the mechanism of TB transmission.

PMID- 22640444
TI  - Molecular epidemiology of tuberculosis in rural Matlab, Bangladesh.
AB  - OBJECTIVE: To characterise and classify clinical isolates collected from
      tuberculosis (TB) patients in rural Bangladesh and to investigate the mode of
      transmission. DESIGN: An epidemiological study using a combination of
      conventional and molecular methods was performed in a rural  population of
      Bangladesh. A total of 168 clinical isolates were collected from TB patients.
      Deletion analysis, used for rapid differentiation of members of the Mycobacterium
      tuberculosis complex, spoligotyping and variable number tandem repeats of
      mycobacterial interspersed repetitive  units (VNTR-MIRU) typing were used.
      RESULTS: Deletion analysis identified all isolates as M. tuberculosis and further
      divided them into 109 strains (65%) carrying the M. tuberculosis deletion region
      1 (TbD1-intact or 'ancestral' strains) and 59 strains (35%) lacking  this region
      (TbD1 or 'modern' strains). MIRU analyses showed that 149 strains (89%) had
      unique patterns, whereas 19 strains (11%) clustered into eight groups. The
      largest cluster comprised five TbD1 strains of the Beijing type. The rate of
      recent transmission was estimated to be  6.5%. CONCLUSIONS: Our results suggest
      that TB in rural Bangladesh is caused primarily by reactivation of latent
      infections involving TbD1 intact strains, overlaid with the recent emergence of
      Beijing strain clusters that include multidrug-resistant isolates.

PMID- 22640445
TI  - Reduction of tuberculosis burden among prisoners in Mongolia: review of case
      notification, 2001-2010.
AB  - Documentation on the TB situation in prisons in developing countries is limited,
      and very few studies have quantitatively evaluated TB control programmes in
      prisons. This study aimed to evaluate TB control in Mongolian prisons by
      analysing routine programmatic data. The TB caseload  in prisons has
      significantly diminished in the last decade, synchronised with policy and
      programmatic development, including systematic entry screening on detention and
      after conviction, and improved living conditions. Improved case detection during
      entry screening may have contributed to  the significant reduction of the TB
      caseload in prisons.

PMID- 22640446
TI  - Knowledge, attitudes and practice concerning tuberculosis in a growing
      industrialised area in Myanmar.
AB  - SETTING: Factories in industrial zones in Yangon, Myanmar, one of the 22 high
      tuberculosis (TB) burden countries. OBJECTIVES: To assess workers' knowledge
      about TB, their health-seeking behaviour, acceptability of TB screening and
      predictors for approval of the dismissal of TB patients. DESIGN: In a cross
      sectional survey, structured interviews with 349 factory workers were followed by
      27 in-depth interviews and two focus group discussions with employers. RESULTS:
      Among 349 workers, 95% perceived TB as being curable, 50% correctly reported air
      as the main mode of transmission  and 68% were aware of free treatment. Although
      88% perceived screening before employment as necessary, only 14% underwent
      screening; 96% were willing to undergo contact screening for TB, but only 55%
      could afford it; 33% agreed with the dismissal of workers with TB, which was
      associated with  lower education, shorter time in employment, not having a
      history of TB contact and unwillingness to work with an index TB case due to fear
      and lack of knowledge. CONCLUSION: More effective communication strategies
      towards factory workers are needed to increase workers' knowledge about 
      transmission and reduce stigma. Employers should be sensitised to protect
      employees with TB and invest in preventive activities.

PMID- 22640447
TI  - Social inequalities in HIV-TB and non-HIV-TB patients in two urban areas in
      southern Spain: multilevel analysis.
AB  - SETTING: Two towns in Campo de Gibraltar, southern Spain, with a small foreign
      population and higher tuberculosis (TB) incidence and human immunodeficiency
      virus (HIV) prevalence than the national average. OBJECTIVE: To determine the
      relationship between HIV-TB and non-HIV-TB incidence and social deprivation and
      other potential individual and contextual determinants. METHODS: In a cross
      sectional longitudinal study, individual TB case variables were identified from
      three sources--routine surveillance, laboratory and hospital discharge records-
      from 1997 to 2007. Community variables were obtained at the census tract level. A
      deprivation index was calculated based on percentages of unemployment, low
      educational level and unskilled labour. Multilevel Poisson models were estimated
      for TB incidence rates for patients with and without HIV. RESULTS: A total of 490
      TB cases were included. Sex and age at individual level and deprivation and
      residence in the port area at census tract level were associated both with HIV
      related TB and with non-HIV-TB. Household crowding contextual variables were also
      associated with HIV-related TB incidence. Full models account for 78.9% and 51.7%
      reductions in second-level variance. CONCLUSION: Socio-economic deprivation is
      associated with higher rates of HIV-TB and non-HIV-TB. Diverse individual and
      contextual potential risk factors suggest different pathways of transmission. It
      is necessary to extend the framework for intervention beyond individual-based
      strategies to the socio-economic contexts in which people live.

PMID- 22640448
TI  - HIV-positive patients treated for multidrug-resistant tuberculosis: clinical
      outcomes in the HAART era.
AB  - SETTING: Multidrug-resistant tuberculosis (MDR-TB) and the human immunodeficiency
      virus (HIV) pose two of the greatest threats to global tuberculosis (TB) control.
      Given expanding global access to antiretroviral therapy (ART) and second-line TB
      drugs, more data are needed on experiences  treating MDR-TB and HIV co-infection
      in resource-poor settings. OBJECTIVE: To describe the clinical characteristics,
      management, outcomes, and factors associated with survival among HIV-positive
      individuals receiving treatment for MDR-TB. DESIGN: This was a retrospective case
      series  of 52 HIV-positive individuals receiving treatment for MDR-TB in Lima,
      Peru. We used Cox proportional hazards regression models to identify risk factors
      for mortality. RESULTS: A total of 31 (57%) of the cohort died on treatment, with
      the majority of deaths due to MDR-TB. Low baseline weight  predicted a three-fold
      increased rate of death (aHR 3.1, 95%CI 1.5-6.7), while individuals receiving
      highly active ART experienced a significantly lower rate of death compared to
      those who were not (aHR 0.4, 95%CI 0.2-0.9). CONCLUSION: Early ART is likely a
      key component of  effective MDR-TB management in co-infected individuals.

PMID- 22640449
TI  - Rifampicin-resistant Mycobacterium tuberculosis: susceptibility to isoniazid and
      other anti-tuberculosis drugs.
AB  - Based on data from 14 Supranational Tuberculosis (TB) Reference Laboratories
      worldwide, the proportion of rifampicin (RMP) resistant isolates that were
      isoniazid (INH) susceptible by phenotypic drug susceptibility testing varied
      widely (0.5-11.6%). RMP-resistant isolates that  were INH-susceptible had
      significantly lower rates of resistance to other first- and second-line anti
      tuberculosis drugs (except rifabutin) compared to multidrug-resistant isolates.
      RMP resistance is not always a good proxy for a presumptive diagnosis of
      multidrug-resistant TB, which has implications  for use of molecular assays that
      identify only RMP resistance-associated DNA mutations.

PMID- 22640450
TI  - Linezolid in the treatment of MDR-TB: a retrospective clinical study.
AB  - BACKGROUND: There is limited information on Chinese patients with multidrug
      resistant tuberculosis (MDR-TB) treated with a linezolid-containing regimen.
      OBJECTIVE: To examine treatment outcomes among MDR-TB patients who were treated
      with linezolid at the Shanghai Pulmonary Hospital,  China. DESIGN: We
      retrospectively reviewed 151 patients who were treated for MDR-TB from 2007 to
      2010. RESULTS: Eighteen MDR-TB patients, including 15 with extensively drug
      resistant TB, received linezolid as part of their individualised treatment
      regimens. Patients had isolates resistant  to a median of 7 drugs (range 5-11).
      Of the 18 cases, 17 had cavitary changes and positive sputum smear microscopy
      results at the time of MDR-TB diagnosis. Culture conversion occurred in all cases
      at a median of 7 weeks. At data censure, 9 of the 18 patients had achieved
      treatment success.  Three continued to receive treatment. There were no deaths.
      Six patients had a poor outcome, including 1 default, 2 treatment failures and 3
      relapses. Side effects occurred in 17 patients, including myelosuppression,
      neurotoxicity and gastrointestinal adverse events. Adverse events were managed 
      by combinations of temporary suspension of linezolid in 1 patient, dose
      adjustment in 17 patients and symptom management in 13 patients. CONCLUSIONS:
      Linezolid may have efficacy in the treatment of MDR-TB, although treatment was
      complicated by adverse events.

PMID- 22640451
TI  - Concordance of programmatic and laboratory-based multidrug-resistant tuberculosis
      treatment outcomes in Peru.
AB  - BACKGROUND: Confirmation of cure for multidrug-resistant tuberculosis (MDR-TB)
      patients requires laboratory tests for Mycobacterium tuberculosis growth on
      culture media. Outcome decisions dictate patient management, and inaccuracies
      place patients at an increased risk of morbidity  and mortality, and may
      contribute to continued transmission of MDR-TB. OBJECTIVE: To examine concordance
      between programmatic and laboratory-based MDR-TB treatment outcomes. METHODS: The
      study population included 1658 MDR-TB patients in Peru treated between 1996 and
      2002 with both program  and laboratory-based outcomes. Laboratory-based outcomes
      were assigned according to international standards requiring at least five
      consecutive negative cultures in the last 12 months of treatment to confirm cure.
      RESULTS: Compared to the global culture-defined standard classification,  only
      1.1% of treatment successes, but 54.3% of failures, were misclassified
      programmatically. Overall, 10.4% of patients identified by a clinician as having
      a successful treatment outcome still had cultures positive for MDR-TB.
      CONCLUSION: Most patients with successful treatment outcomes  by strict culture
      definitions were also classified by clinicians as having successful outcomes.
      However, many culture-confirmed failures were missed. In light of delays and
      incomplete access to culture in MDR-TB programs, efforts should be made to
      improve the accuracy of programmatically determined  treatment outcomes.

PMID- 22640452
TI  - Effectiveness of a training course on the quality assurance of chest radiography
      in the Philippines.
AB  - SETTING: Socio-economically underprivileged areas in urban settings in the
      Philippines. OBJECTIVE: To determine the effectiveness of a training course in
      quality chest radiography (CXR). METHODS: A descriptive, observational
      intervention study in which a questionnaire was administered  to X-ray facility
      staff before training, and CXRs were reviewed before and after a training course
      for radiological technologists in Manila and Quezon City in the Philippines from
      2009 to 2010. Course participants submitted six CXRs, each taken before and after
      training. Two senior radiological  technologists blinded to the CXR profiles
      assessed the CXRs independently, using an assessment sheet developed by the
      Tuberculosis Coalition for Technical Assistance. RESULTS: Forty radiological
      technologists from 10 facilities in Manila City and nine in Quezon City
      participated in the  training. A total of 36 participants submitted the required
      set of CXRs. The assessment indicated that the training effectively improved the
      quality of CXRs in terms of identification marking (Wilcoxon matched-pairs signed
      rank sum test, P = 0.00), contrast (P = 0.00), sharpness  (P = 0.01), artefacts
      (P = 0.00), and the total score of the factors (P = 0.00). CONCLUSION: The
      significant improvement in the total score of assessment factors strongly
      suggests a positive impact of the training course on improving the quality of
      CXRs.

PMID- 22640453
TI  - Assessment of panel slides prepared by phenol ammonium sulphate and NALC methods
      for proficiency testing.
AB  - BACKGROUND: Existing methods for the preparation of panel slides necessitate
      handling high-grade acid-fast bacilli positive sputum samples. OBJECTIVE: To
      compare panel slides prepared using the phenol ammonium sulphate sediment (PhAS)
      method with those prepared using the N-acetyl-L-cysteine  (NALC) method in
      proficiency testing. METHODS: Pooled sputum specimens of known smear-positives
      and -negatives were divided into two parts: one part was used for preparing panel
      slides using the NALC method and the other using PhAS, a non-hazardous method.
      Respectively 413 and 384 smears  of different grades were prepared in three
      batches using the PhAS and NALC methods. Smear grade and quality were recorded by
      121 microscopists during proficiency testing in different states. Agreement
      between reference and reported results was analysed using the kappa test.
      RESULTS: The  overall agreement was 96% for the PhAS method and 91% for the NALC
      method. There were 37 errors using the NALC method compared to 21 for the PhAS
      method (P < 0.223). Smear quality was equally good in both methods; however, the
      cell count was significantly higher in the PhAS than  in the NALC method.
      CONCLUSION: The PhAS method, a non-hazardous procedure with good-quality smears,
      may be further explored for the preparation of panel slides.

PMID- 22640454
TI  - Random blinded rechecking of sputum acid-fast bacilli smear using fluorescence
      microscopy: 8 years' experience.
AB  - BACKGROUND: The Hong Kong TB Reference Laboratory is a high volume laboratory
      examining around 400 sputum acid-fast bacilli smears daily using fluorescence
      microscopy (FM). OBJECTIVE: To assess the effectiveness of blinded rechecking
      applied to FM in a high-throughput laboratory. METHOD: From 2003, 2.5% (5% in
      2003 and 2004) of all smears were randomly selected, relabelled and assigned to
      each technician (rechecker) in turn. These smears were restained and re-examined.
      Discordance between initial screener and rechecker was resolved by a controller.
      RESULTS: From 2003 to  2010, low false-negative (LFN) errors (0.10-0.27%) were
      within the critical values, at 85% (1 year) and 90% (7 years) sensitivity.
      However, LFN error (0.28-0.62%) among recheckers was prominent. There were also
      low false-positive (LFP) cases (0.13-0.75%), but subsequent cultures  showed
      these to be mycobacteria culture-positive. This relatively poor performance among
      the recheckers might be due to background fluorescence increase after restaining
      and/or inefficiency of the rechecking procedure. CONCLUSION: In a high-throughput
      laboratory, blind rechecking is a good  means of quality assurance. To minimise
      false LFP, problems due to restaining should be resolved before blinded
      rechecking can be generally applied in the field for FM where mycobacterial
      cultures are not routinely performed.

PMID- 22640455
TI  - Light-emitting diode with various sputum smear preparation techniques to diagnose
      tuberculosis.
AB  - SETTING: Mawenzi Regional Hospital, northern Tanzania. OBJECTIVE: To determine
      the value of light-emitting diode (LED) microscopy in diagnosing tuberculosis
      (TB) on bleach-treated and direct sputum smears. DESIGN: Sputum samples were
      collected from patients suspected of pulmonary  TB who presented consecutively at
      the laboratory for smear evaluation between December 2009 and February 2010. Four
      smears were prepared from each specimen: conventional Ziehl-Neelsen (ZN), direct
      auramine, bleach centrifugation and bleach short sedimentation auramine smears. A
      light microscope  was used to examine ZN smears and an LED fluorescent microscope
      to examine auramine-stained smears. RESULTS: Of the 267 sputum samples examined,
      respectively 78 (29%), 62 (23%), 74 (28%) and 48 (18%) were acid-fast bacilli
      (AFB) positive by the bleach centrifugation, bleach short sedimentation,  direct
      auramine and ZN methods. Bleach centrifugation identified 30 (11%) more positives
      than ZN microscopy (P < 0.001), but was not superior to the direct auramine
      method (P = 0.46), which yielded 26 (10%) more positives than ZN microscopy (P <
      0.001). Fluorescent  LED required a shorter smear reading time (1.5 min on
      average), while the light microscope took 4 min (P < 0.001). CONCLUSION:
      Fluorescent LED microscopy with direct smear preparation is rapid and effective.
      Further studies are needed to ascertain its performance under routine 
      conditions.

PMID- 22640456
TI  - Distribution of adult respiratory illnesses at a primary health centre in
      Lesotho.
AB  - SETTING: Primary health centre in the highlands of Lesotho. BACKGROUND: There is
      limited information about the relative frequencies of common respiratory
      illnesses in resource-limited settings, particularly in sub-Saharan Africa.
      OBJECTIVE: To examine whether the distribution  of respiratory illnesses in this
      region is unique due to the high prevalence of human immunodeficiency virus
      infection. DESIGN: In a prospective, cross-sectional study of adults and
      adolescents with cough or difficulty breathing recruited from the waiting areas
      of the health centre, the  primary outcome was the respiratory diagnosis for each
      participant, which was based on history, physical examination, response to
      antibiotics and the results of chest radiography (CXR) and sputum examinations.
      RESULTS: Acute respiratory infections accounted for 65% of all diagnoses among 
      696 patients who were evaluated by a clinician and CXR. Pneumonia accounted for
      10% of all diagnoses, and confirmed or probable tuberculosis (TB) accounted for
      13%. Chronic respiratory conditions, including asthma, chronic obstructive
      pulmonary disease, silicosis and old TB, accounted for  14% of all diagnoses.
      Excluding 61 patients with an uninterpretable CXR, 36% (228) of the participants
      had significant pathology on CXR. CONCLUSION: A high proportion of patients
      presenting to a primary health centre in Lesotho with routine respiratory
      complaints have serious respiratory  illnesses.

PMID- 22640457
TI  - Even partial reduction of biomass fuel use may improve the respiratory health of
      rural women in Central India.
AB  - Routine use of biomass fuels in cooking adversely affects respiratory health, but
      whether partial abolition of the biomass use is also detrimental is unknown. We
      conducted a cross-sectional study of 760 women in rural central India: 283 used
      non-biomass fuels (Group A), 225 biomass  and other fuels (Group B), while 252
      exclusively used biomass fuels (Group C). Robust multivariate analyses adjusted
      for age, daily cooking time, cooking experience, marital status, overcrowding and
      education showed that only Group C, and not Group B, had poor respiratory health.
      Our results  indicate that even partial abolition of biomass use may be
      beneficial.

PMID- 22640458
TI  - Management of contacts of multidrug-resistant tuberculosis patients in the
      European Union and European Economic Area.

PMID- 22640459
TI  - Safety and patient perception of an insulin pen with simple memory function for
      children and adolescents with type 1 diabetes--the REMIND study.
AB  - OBJECTIVES: NovoPen Echo * is a durable pediatric insulin pen incorporating half
      unit dosing starting at 0.5 units and a last-dose memory function. The REMIND ?
      (Rating the Effects of Memory function in pediatric INsulin Devices) study
      primarily examined the safety of this new device by collecting data on technical
      complaints (TCs) related to adverse reactions (ARs) during use in a clinical
      setting. METHODS: REMIND was an observational, multicenter study involving
      patients with type 1 diabetes on injection therapy, aged 2-18 years, from Canada,
      Finland, Israel and Sweden. Questionnaires and case report forms were completed
      at baseline and after using NovoPen Echo for 12-18 weeks. RESULTS: In total, 358
      patients participated and 315 completed. No serious ARs were reported. Three ARs
      related to TCs were reported, equated to one every 29 patient-years. Most
      patients found it 'easy' or 'somewhat easy' to read amount (99%) and hours lapsed
      (95%) since last dose using the memory function. The proportion of children self
      injecting was significantly higher (71%) compared with those on previous device
      (66%, p=0.006). 80% of physicians answers reported they could train users in <=10
      minutes. CONCLUSIONS: Only three device safety events were reported for NovoPen
      Echo. Physicians found it easy and quick to educate users. Patients/caregivers
      missed fewer injections and reported greater confidence in managing their insulin
      injections. As this was an observational study without controls or centralized
      laboratory testing, caution should be used in interpreting outcomes in glycemic
      control. Further studies are required to examine the effects of features such as
      memory function and half-unit dosing on HbA1c and hypoglycemia over a longer time
      period.

PMID- 22640460
TI  - Chemotherapy and skin reactions.
AB  - BACKGROUND: New chemotherapic agents and new protocols in oncology have led to an
      increasing survival rate in patients affected by tumors. However, this increased
      use has been accompanied by a growth in the incidence of cutaneous side effects
      and a worsening of patients' quality of life. Appropriate management of skin
      toxicity associated with chemotherapic agents is therefore necessary for suitable
      drug administration and to improve quality of life and clinical outcomes.
      METHODS: We have clinically examined 100 patients affected by cancer, determining
      type, frequency, treatment, and evolution of side effects related to
      chemotherapy. RESULTS: The prevalent cutaneous side effects in patients
      undergoing chemotherapy are skin rash, xerosis, pruritus, paronychia, hair
      abnormality, and mucositis. The clinical cases are reported in detail.
      CONCLUSION: Oncological therapies have become more selective and have low
      systemic toxicity because of their high specificity, but cutaneous side effects
      are common and may worsen the quality of life of these patients.

PMID- 22640461
TI  - Nosocomial transmission of community-acquired methicillin-resistant
      Staphylococcus aureus in a well-infant nursery of a teaching hospital.
AB  - BACKGROUND: Infection due to community-acquired strains of methicillin-resistant
      Staphylococcus aureus (CA-MRSA) has been reported with increasing frequency.
      Herein is described the nosocomial transmission of CA-MRSA involving 13 neonates
      and two mothers in a well-infant nursery in a teaching hospital in Saudi Arabia.
      METHODS: From October to November 2009, temporally related cases of CA-MRSA skin
      and soft-tissue infection occurred in newborns shortly after discharge from a
      well-infant nursery. An outbreak investigation including case identification,
      review of medical records, staff screening, environmental cultures, pulsed-field
      gel electrophoresis, and a case-control study were conducted. Controls were
      selected from among asymptomatic neonates admitted to the same nursery and
      matched for the day of admission. RESULTS: Fifteen subjects were found to be CA
      MRSA positive: 13 neonates and two mothers. The crude attack rate among neonates
      was 5.5% during the outbreak period. All 13 neonates presented with skin and soft
      tissue infection; one of the mothers had mastitis and a breast abscess. The
      source of the outbreak was not evident. Pulsed-field gel electrophoresis showed
      that all of the tested isolates from one strain except one, all contained the
      staphylococcal cassette chromosome mec (SCCmec) type IV. CONCLUSION: MRSA strains
      that initially emerged in the community are now causing disease in health-care
      settings. Adherence to standard infection control practices, including consistent
      hand hygiene, in newborn nurseries is important to prevent transmission in such
      settings.

PMID- 22640463
TI  - Impact on learning of an e-learning module on leukaemia: a randomised controlled
      trial.
AB  - BACKGROUND: e-learning resources may be beneficial for complex or conceptually
      difficult topics. Leukaemia is one such topic, yet there are no reports on the
      efficacy of e-learning for leukaemia. This study compared the learning impact on
      senior medical students of a purpose-built e-learning module on leukaemia,
      compared with existing online resources. METHODS: A randomised controlled trial
      was performed utilising volunteer senior medical students. Participants were
      randomly allocated to Study and Control groups. Following a pre-test on leukaemia
      administered to both groups, the Study group was provided with access to the new
      e-learning module, while the Control group was directed to existing online
      resources. A post-test and an evaluation questionnaire were administered to both
      groups at the end of the trial period. RESULTS: Study and Control groups were
      equivalent in gender distribution, mean academic ability, pre-test performance
      and time studying leukaemia during the trial. The Study group performed
      significantly better than the Control group in the post-test, in which the group
      to which the students had been allocated was the only significant predictor of
      performance. The Study group's evaluation of the module was overwhelmingly
      positive. CONCLUSIONS: A targeted e-learning module on leukaemia had a
      significant effect on learning in this cohort, compared with existing online
      resources. We believe that the interactivity, dialogic feedback and integration
      with the curriculum offered by the e-learning module contributed to its impact.
      This has implications for e-learning design in medicine and other disciplines.

PMID- 22640462
TI  - Glucose transporter/T1R3-expressing cells in rat tracheal epithelium.
AB  - Glucose transport plays an important role in maintaining low sugar concentration
      in airway surface liquid (ASL), which is critical for mucociliary clearance and
      bacterial colonization. Experimental evidence indicates that glucose/hexose
      uptake in lung/airway cells occurs by means of two structurally distinct glucose
      transporter pathways: the Na(+) -dependent glucose transporters (SGLT family) and
      the facilitative glucose transporters (GLUT family). In this study, we examined
      the expression of the major glucose transporters of the intestine, GLUT2, GLUT5,
      SGLT1 and T1R3 taste receptor subunit, in the trachea of rats using
      immunohistochemistry and immunoelectron microscopy, and compared them using
      double-labeled confocal microscopy. We found that GLUT2, GLUT5, SGLT1 and T1R3
      are selectively expressed in different cell types. T1R3 and GLUT2 are
      predominantly expressed in subsets of solitary chemoreceptor cells (SCCs) and
      ciliated cells, GLUT5 is present in subsets of SCCs and in secretory cells, and
      SGLT1 is exclusively expressed in a unique cell type, SCCs. Furthermore, we
      demonstrated that T1R3 is colocalized with SGLT1 in SCCs and with GLUT2
      transporter in ciliated cells. In conclusion, these findings reveal that
      different cell types are associated with the uptake of glucose in ASL and that,
      due to their T1R3 expression, SCCs and ciliated cells are most likely to
      participate in the chemosensory process in ASL.

PMID- 22640464
TI  - Linear models for breeding values prediction in haplotype-assisted selection - an
      analysis of QTL-MAS Workshop 2011 Data.
AB  - BACKGROUND: The aim of this study was to estimate haplotype effects and then to
      predict breeding values using linear models. The haplotype based analysis enables
      avoidance of loosing information due to linkage disequilibrium between single
      markers. There are also less explanatory variables in the linear model which
      makes the estimation more reliable. METHODS: Different methods and criteria for
      marker and haplotype selection were considered. First, markers with MAF lower
      than 5% where excluded from the data set. Then, SNPs in complete linkage
      disequilibrium where selected. Next step was to construct haplotypes and to
      estimate their frequencies basing on selected SNPs. The haplotypes with a
      frequency lower than 1% were not considered in further analysis. Chosen
      haplotypes were used as the explanatory variables in the linear models for
      breeding values prediction. Linear models with fixed and random haplotype effects
      as well as animal model were tested. RESULTS: The number of markers was limited
      to 1206, 1189, 1249, 1288 and 1167 for chromosome 1, 2, 3, 4 and 5, respectively
      due to MAF criterion. In total 409 subsets of SNPs with r2=1 were found. 1476
      haplotypes with different lengths were inferred. The frequencies of 817
      haplotypes were higher than 1% - 184 for the first chromosome, 172 for the
      second, 131 for the third, 146 for the forth and 184 haplotypes for the fifth
      chromosome. The haplotype effects estimated using random models were comparable
      and more precise in prediction for individuals with unknown phenotypes. A few
      haplotypes with large effects were found when their effects were defined as fixed
      in the linear model . The correlations of the predicted breeding values with true
      breeding values were not that high. This could be brought about by selection
      criteria imposed on the genotype data which led to substantial reduction of
      number of markers. CONCLUSIONS: Although not many markers were considered in the
      study, the results obtained show that the implemented approach can be considered
      as quite promising. The haplotype approach let to avoid high dimensional models
      as compared with single SNPs models.

PMID- 22640465
TI  - What dietary modification best improves insulin sensitivity and why?
AB  - Insulin resistance (IR) has been proposed as the strongest single predictor for
      incident type 2 diabetes and is mainly caused by adiposity as a result of chronic
      excessive energy intake. Loss of body weight and fat mass improve insulin
      sensitivity. However, independent of energy intake and changes in body
      weight/composition, dietary content and specific metabolic effects of certain
      nutrients may play significant additional roles in influencing IR. These effects
      are mainly relatively modest, with modulation of IR and diabetes risk within the
      range of 10-30%, but could be of major relevance on a population level. Examples
      include dietary concepts and patterns such as the traditional Mediterranean diet;
      the isoenergetic modulation of the composition of types of fatty acids in the
      diet; low-carbohydrate-high-protein diets; the quality of carbohydrate-rich
      foods, which includes the concepts of glycaemic index (GI) and glycaemic load;
      and, not necessarily related to the GI concept, specific metabolic effects of
      high-fibre diets, with relevant differences between the type of fibre consumed.
      Effects of further selected foods (e.g. coffee, tea and nuts) and micronutrients
      (e.g. magnesium, selenium and zinc) on the modulation of IR have been reviewed
      elsewhere. This study focuses on changes in IR by isoenergetic modulation of the
      main macronutrients (fat, carbohydrates including dietary fibre, and dietary
      protein), with discussion of novel concepts and the potential interplay of food
      components in the current dietary concepts.

PMID- 22640467
TI  - Patient outcomes and thoracic aortic volume and morphologic changes following
      thoracic endovascular aortic repair in patients with complicated chronic type B
      aortic dissection.
AB  - OBJECTIVE: True and false lumen changes and patient outcomes following thoracic
      endovascular aortic repair (TEVAR) for patients with stable type B dissection
      have been described by the The Investigation of Stent Grafts in Aortic Dissection
      (INSTEAD) trial. However, these changes have not been described in TEVAR patients
      treated for complications of chronic dissection. METHODS: A single-institution
      study was conducted of 73 prospectively evaluated patients treated for
      complications of chronic type B dissection from 2002 to 2010. Spiral computed
      tomography reconstructions using M2S (Medical Media Systems, West Lebanon, NH)
      were analyzed for sequential changes in aortic volume and diameter during patient
      follow-up. Changes in aortic volume and diameter were tabulated as a percent
      change from preoperative values. Patient outcomes were determined by sequential
      evaluations postprocedure. RESULTS: TEVAR was successfully performed in 72 out of
      the 73 patients (99%). Indications for intervention were aortic enlargement (n =
      62), failure of medical management (n = 7), and perforation (n = 4). The 30-day
      all-cause mortality rate was 14%; events were due to retrograde dissection (n =
      4), cardiac-related (n = 4), and rupture (n = 2). Eleven out of the 72 patients
      (15%) required a secondary procedure for endoleak (n = 7) and persistent distal
      perfusion of the false lumen (n = 4). Mean percentage expansion of the thoracic
      true lumen was noted during the follow-up period: 38%, 46%, 71%, and 114% at 1-,
      3-, 6-, and 12-month follow-up, respectively. Concomitant regression of the
      thoracic false lumen of -65%, -68%, -84%, and -84% was observed at the same
      intervals, respectively. Patients with an initial extension of the thoracic
      dissection into the infrarenal aorta (n = 46) had an increase in mean percentage
      change of aortic diameter and volume to 21% and 17% at 1 year, respectively. By
      contrast, in the patient group without infrarenal dissection (n = 14), the
      infrarenal aortic diameter and volume remained relatively unchanged at 3% and 
      0.9%, respectively, at 1-year postintervention. CONCLUSIONS: TEVAR is a potential
      treatment option for patients experiencing complications of chronic type B
      dissection. During follow-up, there is a predictable expansion of the thoracic
      true lumen and regression of the thoracic false lumen. These findings correlate
      with those of the INSTEAD trial, which demonstrated false lumen regression and
      true lumen expansion in a cohort of patients with stable type B dissection.
      However, many patients with extension of thoracic dissection into the infrarenal
      aorta demonstrate continued aortic dilation and, on occasion, the need for
      secondary intervention for persistent distal perfusion. Further analysis is
      needed in this subgroup of patients so as to better determine potential
      predictors and the clinical significance of post-TEVAR infrarenal expansion.
      Moreover, further investigations may support a role for secondary endovascular
      intervention in remedying persistent infrarenal aortic expansion after TEVAR for
      chronic dissection.

PMID- 22640469
TI  - Is there adaptation of the exocrine pancreas in wild animal? The case of the Roe
      deer.
AB  - BACKGROUND: Physiology of the exocrine pancreas has been well studied in domestic
      and in laboratory animals as well as in humans. However, it remains quite unknown
      in wildlife mammals. Roe deer and cattle (including calf) belong to different
      families but have a common ancestor. This work aimed to evaluate in the Roe deer,
      the adaptation to diet of the exocrine pancreatic functions and regulations
      related to animal evolution and domestication. RESULTS: Forty bovine were
      distributed into 2 groups of animals either fed exclusively with a milk formula
      (monogastric) or fed a dry feed which allowed for rumen function to develop, they
      were slaughtered at 150 days of age. The 35 Roe deer were wild animals living in
      the temperate broadleaf and mixed forests, shot during the hunting season and
      classified in two groups adult and young. Immediately after death, the pancreas
      was removed for tissue sample collection and then analyzed. When expressed in
      relation to body weight, pancreas, pancreatic protein weights and enzyme
      activities measured were higher in Roe deer than in calf. The 1st original
      feature is that in Roe deer, the very high content in pancreatic enzymes seems to
      be related to specific digestive products observed (proline-rich proteins largely
      secreted in saliva) which bind tannins, reducing their deleterious effects on
      protein digestion. The high chymotrypsin and elastase II quantities could allow
      recycling of proline-rich proteins. In contrast, domestication and rearing cattle
      resulted in simplified diet with well digestible components. The 2nd feature is
      that in wild animal, both receptor subtypes of the CCK/gastrin family peptides
      were present in the pancreas as in calf, although CCK-2 receptor subtype was
      previously identified in higher mammals. CONCLUSIONS: Bovine species could have
      lost some digestive capabilities (no ingestion of great amounts of tannin-rich
      plants, capabilities to secrete high amounts of proline-rich proteins) compared
      with Roe deer species. CCK and gastrin could play an important role in the
      regulation of pancreatic secretion in Roe deer as in calf. This work, to the best
      of our knowledge is the first study which compared the Roe deer adaptation to
      diet with a domesticated animal largely studied.

PMID- 22640471
TI  - CCS52 and DEL1 genes are key components of the endocycle in nematode-induced
      feeding sites.
AB  - The establishment of galls and syncytia as feeding sites induced by root-knot and
      cyst nematodes, respectively, involves a progressive increase in nuclear and
      cellular size. Here we describe the functional characterization of endocycle
      activators CCS52A, CCS52B and a repressor of the endocycle, DEL1, during two
      types of nematode feeding site development in Arabidopsis thaliana. In situ
      hybridization analysis showed that expression of CCS52A1 and CCS52B was strongly
      induced in galls and syncytia and DEL1 was stably but weakly expressed throughout
      feeding site development. Down-regulation and over-expression of CCS52 and DEL1
      in Arabidopsis drastically affected giant cell and syncytium growth, resulting in
      restrained nematode development, illustrating the need for mitotic activity and
      endo-reduplication for feeding site maturation. Exploiting the mechanism of endo
      reduplication may be envisaged as a strategy to control plant-parasitic
      nematodes.

PMID- 22640470
TI  - Decision support at home (DS@HOME)--system architectures and requirements.
AB  - BACKGROUND: Demographic change with its consequences of an aging society and an
      increase in the demand for care in the home environment has triggered intensive
      research activities in sensor devices and smart home technologies. While many
      advanced technologies are already available, there is still a lack of decision
      support systems (DSS) for the interpretation of data generated in home
      environments. The aim of the research for this paper is to present the state-of
      the-art in DSS for these data, to define characteristic properties of such
      systems, and to define the requirements for successful home care DSS
      implementations. METHODS: A literature review was performed along with the
      analysis of cross-references. Characteristic properties are proposed and
      requirements are derived from the available body of literature. RESULTS: 79
      papers were identified and analyzed, of which 20 describe implementations of
      decision components. Most authors mention server-based decision support
      components, but only few papers provide details about the system architecture or
      the knowledge base. A list of requirements derived from the analysis is
      presented. Among the primary drawbacks of current systems are the missing
      integration of DSS in current health information system architectures including
      interfaces, the missing agreement among developers with regard to the
      formalization and customization of medical knowledge and a lack of intelligent
      algorithms to interpret data from multiple sources including clinical application
      systems. CONCLUSIONS: Future research needs to address these issues in order to
      provide useful information--and not only large amounts of data--for both the
      patient and the caregiver. Furthermore, there is a need for outcome studies
      allowing for identifying successful implementation concepts.

PMID- 22640472
TI  - An assessment of the Zimbabwe ministry of health and child welfare provider
      initiated HIV testing and counselling programme.
AB  - BACKGROUND: Provider-initiated HIV testing and counselling (PITC) is widely
      recommended to ensure timely treatment of HIV. The Zimbabwe Ministry of Health
      introduced PITC in 2007. We aimed to evaluate institutional capacity to implement
      PITC and investigate patient and health care worker (HCW) perceptions of the PITC
      programme. METHODS: Purposive selection of health care institutions was conducted
      among those providing PITC. Study procedures included 1) assessment of
      implementation procedures and institutional capacity using a semi-structured
      questionnaire; 2) in-depth interviews with patients who had been offered HIV
      testing to explore perceptions of PITC, 3) Focus group discussions with HCW to
      explore views on PITC. Qualitative data was analysed according to Framework
      Analysis. RESULTS: Sixteen health care institutions were selected (two central,
      two provincial, six district hospitals; and six primary care clinics). All
      institutions at least offered PITC in part. The main challenges which prevented
      optimum implementation were shortages of staff trained in PITC, HIV rapid testing
      and counselling; shortages of appropriate counselling space, and, at the time of
      assessment, shortages of HIV test kits. Both health care workers and patients
      embraced PITC because they had noticed that it had saved lives through early
      detection and treatment of HIV. Although health care workers reported an increase
      in workload as a result of PITC, they felt this was offset by the reduced number
      of HIV-related admissions and satisfaction of working with healthier clients.
      CONCLUSION: PITC has been embraced by patients and health care workers as a life
      saving intervention. There is need to address shortages in material, human and
      structural resources to ensure optimum implementation.

PMID- 22640473
TI  - Heterogeneity in memory training improvement among older adults: a latent class
      analysis.
AB  - This study investigated the extent to which older adults' associative memory
      functioning can be modified through instruction and practice based on
      individuals' memory status. Here 42 younger adults and 42 older adults performed
      four tasks that measured strategic and binding aspects of memory. With latent
      class analysis, two classes of older adults were identified. The first class
      showed higher memory functioning similar to younger adults, while the second
      class was characterised by lower memory functioning. A subsequent analysis
      examined whether the high- and low-performing older adults differ in patterns of
      gain from receiving instruction and practice on a mnemonic strategy. The results
      revealed that high-performing older adults, similar to younger adults, showed
      higher associative memory performance under explicit intentional encoding
      instruction and after extensive practice of the strategy. In contrast, low
      performing older adults benefited more from directed instruction of the strategy.
      The results are discussed in relation to individual differences in the functional
      status of mechanisms underlying memory functioning, and how these differences may
      lead to compensation or magnification of training gain. The present findings
      highlight the importance of considering differential memory processes to develop
      specific training paradigms that target the processes that show the most
      prominent decline.

PMID- 22640466
TI  - Cost-effectiveness of open versus endovascular repair of abdominal aortic
      aneurysm in the OVER trial.
AB  - OBJECTIVE: This study was conducted to determine the costs and comparative cost
      effectiveness of two methods of abdominal aortic aneurysm (AAA) repair in the
      Open Versus Endovascular Repair (OVER) Veterans Affairs (VA) Cooperative Study, a
      multicenter randomized trial of 881 patients. METHODS: The primary outcomes of
      this analysis were mean total health care cost per life-year and per quality
      adjusted life-year (QALY) from randomization to 2 years after. QALYs were
      calculated from EuroQol (EQ)-5D questionnaires collected at baseline and
      annually. Health care utilization data were obtained directly from patients and
      from national VA and Medicare data sources. VA costs were obtained from national
      VA sources using methods previously developed by the VA Health Economics Resource
      Center. Costs for non-VA care were determined from Medicare claims data or
      billing data from the patient's health care providers. RESULTS: After 2 years of
      follow-up, mean life-years were 1.78 in the endovascular repair group and 1.74 in
      the open repair group (difference, 0.04; 95% confidence interval [CI], -0.03 to
      0.09; P = .29). Mean QALYs were 1.462 in the endovascular group and 1.461 in the
      open group (difference adjusting for baseline EQ-5D score, 0.006; 95% CI, -0.038
      to 0.052; P = .78). Mean graft costs were higher in the endovascular group
      ($14,052 vs $1363; P < .001), but length of stay was shorter (5.0 vs 10.5 days; P
      < .001), resulting in a lower mean cost of the hospital admission for the AAA
      procedure in the endovascular repair group of $37,068 vs $42,970 (difference, 
      $5901; 95% CI, -$12,135 to -$821; P = .04). After 2 years, total health care
      costs remained lower in the endovascular group, but the difference was no longer
      significant (-$5019; 95% CI, -$16,720 to $4928; P = .35). The probability of
      endovascular repair being less costly and more effective was 70.9% for life-years
      and 51.4% for QALYs. CONCLUSIONS: In this multicenter randomized trial,
      endovascular AAA repair resulted in lower cost and better survival than open
      repair after the initial hospitalization for repair; but after 2 years, survival,
      quality of life, and costs were not significantly different between the two
      treatments.

PMID- 22640474
TI  - Group I mGluR antagonist rescues the deficit of D1-induced LTP in a mouse model
      of fragile X syndrome.
AB  - BACKGROUND: Fragile X syndrome (FXS) is caused by the absence of the mRNA-binding
      protein Fragile X mental retardation protein (FMRP), encoded by the Fmr1 gene.
      Overactive signaling by group 1 metabotropic glutamate receptor (Grp1 mGluR)
      could contribute to slowed synaptic development and other symptoms of FXS. Our
      previous study has identified that facilitation of synaptic long-term
      potentiation (LTP) by D1 receptor is impaired in Fmr1 knockout (KO) mice.
      However, the contribution of Grp1 mGluR to the facilitation of synaptic
      plasticity by D1 receptor stimulation in the prefrontal cortex has been less
      extensively studied. RESULTS: Here we demonstrated that DL-AP3, a Grp1 mGluR
      antagonist, rescued LTP facilitation by D1 receptor agonist SKF81297 in Fmr1KO
      mice. Grp1 mGluR inhibition restored the GluR1-subtype AMPA receptors surface
      insertion by D1 activation in the cultured Fmr1KO neurons. Simultaneous treatment
      of Grp1 mGluR antagonist with D1 agonist recovered the D1 receptor signaling by
      reversing the subcellular redistribution of G protein-coupled receptor kinase 2
      (GRK2) in the Fmr1KO neurons. Treatment of SKF81297 alone failed to increase the
      phosphorylation of NR2B-containing N-methyl D-aspartate receptors (NMDARs) at Tyr
      1472 (p-NR2B-Tyr1472) in the cultures from KO mice. However, simultaneous
      treatment of DL-AP3 could rescue the level of p-NR2B-Tyr1472 by SKF81297 in the
      cultures from KO mice. Furthermore, behavioral tests indicated that simultaneous
      treatment of Grp1 mGluR antagonist with D1 agonist inhibited hyperactivity and
      improved the learning ability in the Fmr1KO mice. CONCLUSION: The findings
      demonstrate that mGluR1 inhibition is a useful strategy to recover D1 receptor
      signaling in the Fmr1KO mice, and combination of Grp1 mGluR antagonist and D1
      agonist is a potential drug therapy for the FXS.

PMID- 22640475
TI  - Post-myocardial infarction hormone therapy revisited.
AB  - Current guidelines recommend that postmenopausal hormone therapy should not be
      used in the setting of secondary prevention of coronary heart disease, and that
      it should be stopped when an acute coronary event occurs. Reviewing the available
      data on the issue of discontinuation of therapy in post-myocardial infarction
      patients shows that the basis for this recommendation is not so solid and clear
      cut. In fact, the few relevant studies concluded that cessation of hormone
      therapy carried no benefit, and perhaps even caused some adverse cardiac events,
      when compared to women who continued with treatment after they suffered a
      coronary event. The following article uses a recently published study as an
      opportunity to review this topic. Based on the literature, my personal view is
      that long-term hormone users should not automatically withhold therapy post
      myocardial infarction, but careful individual evaluation and consideration should
      precede any decision.

PMID- 22640476
TI  - The bioelectrical impedance phase angle as an indicator of undernutrition and
      adverse clinical outcome in cardiac surgical patients.
AB  - BACKGROUND & AIMS: In cardiac surgical patients, undernutrition increases the
      risk of adverse clinical outcome. We investigated whether the bioelectrical
      impedance phase angle is an indicator of undernutrition and clinical outcome in
      cardiac surgery. METHODS: In 325 cardiac surgical patients, we prospectively
      analyzed the associations between a preoperative low phase angle, measured by
      bioelectrical impedance spectroscopy, and well-established indicators of
      undernutrition such as body mass index (kg/m(2)), unintended weight loss, and fat
      free mass index (kg/m(2)), and muscle strength (handgrip strength (kg)), immune
      function (C-reactive protein and albumin), and adverse clinical outcomes.
      RESULTS: A low phase angle (<5.38 degrees ) was present in 29.8% (n = 96) of the
      patients, and was associated with low body mass index (p < 0.001), low fat free
      mass index (p < 0.001), and less handgrip strength (p = 0.063), but not with
      unintended weight loss or immune function. Furthermore, a preoperative low phase
      angle was associated with a prolonged intensive care unit and hospital stay (adj.
      hazard ratio: 0.68; 95%CI: 0.49-0.94; p = 0.020 and adj. hazard ratio: 0.74;
      95%CI: 0.55-0.99; p = 0.048, respectively). CONCLUSIONS: A preoperative low
      bioelectrical impedance phase angle is associated with undernutrition, and
      increases the risk of adverse clinical outcome after cardiac surgery. The phase
      angle might help to identify undernourished cardiac surgical patients.

PMID- 22640477
TI  - Protein recommendations in the ICU: g protein/kg body weight - which body weight
      for underweight and obese patients?

PMID- 22640479
TI  - Molecular Dynamics Study of the Effect of the gamma-Abu Insert on the
      Conformational Behavior of the Glycopeptide Dendrimers Based on the Oligolysine
      Scaffold in N, N'-dimethylformamide.
AB  - Abstract   Glycodendrimers bearing Tn (alpha-D-GalNAc-(1->O)-Ser/Thr), an
      identified tumor-associated carbohydrate antigen, hold promise in the post
      surgery treatment of a variety of tumors such as metastatic breast cancer. We
      used molecular dynamics (MD) techniques to examine structural differences taking
      place during synthesis of two classes of tetravalent Multiple Antigen
      Glycopeptides (MAG) that differ only by the y-Abu insert in the structure of the
      oligolysine core. Each of the selected intermediates of the synthesis was
      modeled, subjected to the 2 ns run in N,N'-dimethylformamide (DMF) and
      geometrically characterized. We characterized: a) distances of free, or extended
      termini from the anchor, b) interatomic distances between free or substituted N
      termini, c) radius of gyration and d) spatial distribution of molecular density.
      A detailed conformational analysis of 16 glycodendrimers shows the distinct
      behavior of the inserted vs. non-inserted constructs already during the first
      steps of the modeled synthesis. It suggests that the character as well as the
      length of the insert has a major impact on the spatial characteristics and
      behavior of the dendritic molecules. The inserts can, in principle, increase a
      tendency of dendrimers to establish a high-density core, which is similar to the
      effect of a higher generation.

PMID- 22640478
TI  - Sequencing of BRAF inhibitors and ipilimumab in patients with metastatic
      melanoma: a possible algorithm for clinical use.
AB  - BACKGROUND: Ipilimumab and vemurafenib have both been shown to improve survival
      in phase III trials of patients with metastatic melanoma. Although vemurafenib is
      associated with a rapid onset of activity, responses are often of limited
      duration. Conversely, responses to ipilimumab take time to develop, but can be
      durable. Currently, limited data exist on the sequencing of these agents in
      patients with the BRAFV600 mutation. The aim of this analysis was to identify
      factors that could potentially be used to optimise the order in which ipilimumab
      and BRAF inhibitors are administered in this patient population. METHODS: This
      was a retrospective, single-institution, analysis of patients treated with
      vemurafenib 960 mg or dabrafenib 150 mg twice-daily and ipilimumab 3 mg/kg every
      3 weeks for 4 doses as part of a clinical trial or expanded access program.
      Eligible patients tested positive for the BRAFV600 mutation and had sequentially
      received treatment with vemurafenib or dabrafenib followed by ipilimumab, or vice
      versa. RESULTS: In total, 34 BRAF-mutation positive patients were eligible,
      comprising six patients who received ipilimumab followed by a BRAF inhibitor, and
      28 patients treated with a BRAF inhibitor who subsequently received ipilimumab.
      Of these 28 patients, 12 (43%) had rapid disease progression resulting in death
      and were unable to complete ipilimumab treatment as per protocol. These patients
      were classified as having rapid disease progression. Median overall survival for
      rapid progressors was 5.7 months (95% CI: 5.0-6.3), compared with 18.6 months
      (95% CI: 3.2-41.3; p < 0.0001) for those patients who were able to complete
      ipilimumab treatment. Baseline factors associated with rapid progression were
      elevated lactate dehydrogenase, a performance status of 1 and the presence of
      brain metastases. Patients were more likely to have rapid disease progression if
      they had at least two of these risk factors at baseline. CONCLUSIONS: Our
      analysis suggests it may be possible to identify those patients at high risk of
      rapid disease progression upon relapse with a BRAF inhibitor who might not have
      time to subsequently complete ipilimumab treatment. We hypothesise that these
      BRAF-mutation positive patients may benefit from being treated with ipilimumab
      first.

PMID- 22640480
TI  - Modeling of Neuropeptide Receptors Y1, Y4, Y5, and Docking Studies with
      Neuropeptide Antagonist Analogues: Implications for Selectivity.
AB  - Abstract   Neuropeptide Y (NPY), receptors belong to the G-protein coupled
      receptor superfamily. NPY mediates several physiological responses, such as blood
      pressure, food intake, sedation. These actions of NPY are mediated by six
      receptor subtypes denoted as Y(1)-Y(5) and y(6). Modeling of receptor subtypes
      and binding site identification is an important step in developing new
      therapeutic agents. We have attempted to model the three NPY receptor types, Y1,
      Y4, and Y5 using homology modeling and threading methods. The models are
      consistent with previously reported experimental evidence. To understand the
      interaction and selectivity of NPY analogues with different neuropeptide
      receptors, docking studies of two neuropeptide analogues (BVD10 and BVD15) with
      receptors Y1 and Y4 were carried out. Results of the docking studies indicated
      that the interaction of ligands BVD10 and BVD15 with Y1 and Y4 receptors are
      different. These results were evaluated for selectivity of peptide analogues
      BVD10 and BVD15 towards the receptors.

PMID- 22640481
TI  - Influence of outdoor NO2 exposure on asthma in childhood: meta-analysis.
AB  - BACKGROUND: It has long been assumed that the development of childhood asthma is
      related to exposure to environmental chemicals, but it has thus far not been
      possible to unequivocally establish this suspected relationship using individual
      studies. Moreover, studies of children have been scanty and unreliable due to the
      large diversity of research environments and subject cohorts. The aim of the
      current study was to clarify this relationship for one factor by means of a meta
      analysis of studies investigating the influence of NO(2) exposure on
      symptomatology of childhood asthma. METHODS: Two electronic databases (MEDLINE
      and EMBASE) were searched for literature on relationships between environmental
      chemical exposure and development of childhood asthma using the MeSH terms
      'nitrogen dioxide' and 'asthma'. This was done according to the MOOSE guidelines
      for meta-analyses of observational studies. RESULTS: A total of 130 papers were
      retrieved, of which 12 met the selection criteria. These papers described
      observational studies from seven countries. Study subjects were 97,932 ordinary
      children aged 0-18 years. Using random model analysis, the odds ratio (OR) for
      asthma development due to an increment of 10 p.p.b. NO(2) was 1.135 with a 95%
      confidence interval [CI] of 1.031-1.251 (P= 0.01), while the OR for wheezing
      symptoms was 1.052 with a 95%CI of 1.020-1.085 (P= 0.001). It is therefore
      evident that NO(2) exposure does influence the development of asthma in ordinary
      children. CONCLUSIONS: Exposure to NO(2) in the air significantly influences the
      development of childhood asthma and symptoms of wheezing.

PMID- 22640482
TI  - Sleep disturbances and depressive symptoms: an investigation of their
      longitudinal association in a representative sample of the UK general population.
AB  - BACKGROUND: It has been argued that sleep disturbances are a risk factor for
      depression but previous longitudinal studies have had limitations and not
      addressed alternative explanations. The aim of this study was to examine the
      longitudinal association between sleep disturbances and depressive symptoms in a
      nationally representative sample. METHOD: Data from the 18-month follow-up of the
      UK National Psychiatric Morbidity survey were used (n = 2406). Sleep
      disturbances, depressive and other psychiatric symptoms (fatigue, concentration
      problems, irritability, anxiety and pain symptoms) were assessed using the
      Revised Clinical Interview Schedule (CIS-R). The bidirectional association
      between symptoms was investigated with logistic regression analyses and path
      analysis. RESULTS: Sleep disturbances and depressive symptoms were correlated
      with each other cross-sectionally (r = 0.52, p < 0.001). In the longitudinal
      analysis, sleep disturbances at baseline did not predict depressive symptoms at
      follow-up [odds ratio (OR) 1.27, 95% confidence interval (CI) 0.51-3.19] and the
      same was observed for the reciprocal association (OR 0.87, 95% CI 0.56-1.35). In
      the path analysis, the reciprocal model did not have a better fit compared to the
      simpler first-order model without cross-lagged paths. The path from sleep
      disturbances at baseline to depressive symptoms at follow-up had a minimal
      contribution to the explained variance of the latter (<1%). CONCLUSIONS: Previous
      studies may have overestimated the importance of sleep disturbances as an
      independent risk factor of depression. The strong cross-sectional association is
      compatible with sleep disturbances being either a prodromal or a residual symptom
      of depression and this may have implications for recognition and treatment of
      depression.

PMID- 22640483
TI  - Dydrogesterone does not reverse the cardiovascular benefits of percutaneous
      estradiol.
AB  - OBJECTIVE: To evaluate the influence of dydrogesterone on estimated
      cardiovascular risk of users of hormone replacement therapy (HRT) (with
      percutaneous 17beta-estradiol in monotherapy and in combination with
      dydrogesterone) and HRT non-users through the Framingham score tool for a period
      of 2 years. METHODS: Framingham scores were calculated from the medical records
      of patients treated for at least 2 years with 17beta-estradiol alone or in
      combination with dydrogesterone, along with HRT non-users, through the analysis
      of patient medical records, followed for at least 2 years at Instituto Estadual
      de Diabetes e Endocrinologia Luiz Capriglione. RESULTS: Improvements in lipid
      profile, glucose and blood pressure levels, which reduced the estimated
      cardiovascular risk, were observed in the 17beta-estradiol group. Similar changes
      were observed in the users of 17beta-estradiol + dydrogesterone, suggesting that
      this progestogen does not attenuate the effects caused by 17beta-estradiol.
      CONCLUSIONS: Both HRT groups showed a reduction in their Framingham score. In
      contrast to data from other HRT investigations on cardiovascular risk, these
      formulations proved to be safe, even in the first year of use.

PMID- 22640484
TI  - Phacoemulsification and +14 diopter intraocular lens placement in a Saddlebred
      foal.
AB  - A 2-month-old, 110-kg Saddlebred filly presented for evaluation of bilateral
      cataracts. A hypermature cataract in the left eye (OS) and an incipient nuclear
      cataract in the right eye (OD) were diagnosed. Electroretinography and ocular
      ultrasound revealed no contraindications for surgical removal of the cataractous
      lens OS. Phacoemulsification and implantation of a +14 diopter (D) intraocular
      lens (IOL) OS were performed at 4 months of age without complication, with the
      exception of a partial iridectomy performed on a small iris section that
      prolapsed through the corneal incision. Complete ophthalmic examinations,
      including ocular ultrasound and streak retinoscopy, were performed 1, 2, 6 weeks,
      4 months, 1, and 2 years postoperatively. Diffuse corneal edema and a superficial
      corneal ulcer developed OS during the early postoperative period and resolved
      without complication. Dyscoria was identified owing to anterior synechia of the
      dorsomedial iris at the incision site. Two years after surgery, menace response,
      palpebral reflex, dazzle reflex, and pupillary light reflexes were present in
      both eyes (OU). The IOL remained centrally positioned within the capsule, with
      mild anterior tilting of the superior portion of the IOL and mild fibrosis of the
      lens capsule. The postoperative net refractive error was +0.31 D OS. Based on
      this report, a +14 D IOL may be the appropriate choice following lens extraction
      in a foal to achieve refraction near emmetropia at maturity. To our knowledge,
      this is the first report of phacoemulsification and IOL implantation in a foal
      with long-term follow-up.

PMID- 22640486
TI  - Biases in comparative analyses of extinction risk: mind the gap.
AB  - 1. Comparative analyses are used to address the key question of what makes a
      species more prone to extinction by exploring the links between vulnerability and
      intrinsic species' traits and/or extrinsic factors. This approach requires
      comprehensive species data but information is rarely available for all species of
      interest. As a result comparative analyses often rely on subsets of relatively
      few species that are assumed to be representative samples of the overall studied
      group. 2. Our study challenges this assumption and quantifies the taxonomic,
      spatial, and data type biases associated with the quantity of data available for
      5415 mammalian species using the freely available life-history database
      PanTHERIA. 3. Moreover, we explore how existing biases influence results of
      comparative analyses of extinction risk by using subsets of data that attempt to
      correct for detected biases. In particular, we focus on links between four
      species' traits commonly linked to vulnerability (distribution range area, adult
      body mass, population density and gestation length) and conduct univariate and
      multivariate analyses to understand how biases affect model predictions. 4. Our
      results show important biases in data availability with c.22% of mammals
      completely lacking data. Missing data, which appear to be not missing at random,
      occur frequently in all traits (14-99% of cases missing). Data availability is
      explained by intrinsic traits, with larger mammals occupying bigger range areas
      being the best studied. Importantly, we find that existing biases affect the
      results of comparative analyses by overestimating the risk of extinction and
      changing which traits are identified as important predictors. 5. Our results
      raise concerns over our ability to draw general conclusions regarding what makes
      a species more prone to extinction. Missing data represent a prevalent problem in
      comparative analyses, and unfortunately, because data are not missing at random,
      conventional approaches to fill data gaps, are not valid or present important
      challenges. These results show the importance of making appropriate inferences
      from comparative analyses by focusing on the subset of species for which data are
      available. Ultimately, addressing the data bias problem requires greater
      investment in data collection and dissemination, as well as the development of
      methodological approaches to effectively correct existing biases.

PMID- 22640485
TI  - Oncolytic adenovirus armed with IL-24 inhibits the growth of breast cancer in
      vitro and in vivo.
AB  - BACKGROUND: Interleukin-24 (IL-24) is a cytokine that belongs to the IL-10
      family. It can selectively induce cancer cell apoptosis which has been utilized
      as a cancer gene therapy strategy. METHODS: A recombinant type five adenovirus
      containing IL-24 gene (designated CNHK600-IL24) was constructed, whose
      replication is activated only in tumor cells. The replication of CNHK600-IL24 in
      breast tumor cells and fibroblasts were assessed by TCID50 and MTT assay; the
      secretion of IL-24 was measured by ELISA and western blotting. The in vivo anti
      tumor effect of CNHK600-IL24 was investigated in nude mice carrying orthotopic or
      metastatic breast tumor. RESULTS: We observed that CNHK600-IL24 could replicate
      efficiently and resulted in high level IL-24 expression and massive cell death in
      human breast cancer cell MDA-MB-231 but not in normal fibroblast cell MRC-5. In
      addition, orthotopic breast tumor growth in the nude mice model was significantly
      suppressed when CNHK600-IL24 was administered. In the metastatic model generated
      by tail vein injection, CNHK600-IL24 virotherapy significantly improved survival
      compared with the same virus expressing EGFP (median survival CNHK600-IL24, 55
      days vs. CNHK600-EGFP, 41 day, p < 0.05 Mantal-Cox test). A similar phenomenon
      was observed in the metastatic model achieved by left ventricular injection as
      suggested by in vivo luminescence imaging of tumor growth. CONCLUSION: The
      oncolytic adenovirus armed with IL-24, which exhibited enhanced anti-tumor
      activity and improved survival, is a promising candidate for virotherapy of
      breast cancer.

PMID- 22640487
TI  - Retrieval-induced forgetting, delay, and sleep.
AB  - Retrieval-induced forgetting (RIF) refers to the finding that retrieval of a
      subset of previously studied material can cause forgetting of related unpractised
      material. Prior work on the role of delay between practice and test for RIF
      reported mixed results. Whereas some studies found RIF to be a relatively
      transient phenomenon, others found RIF to persist over time. We examined whether
      the persistence of RIF can depend on whether wakefulness or sleep follows
      retrieval practice. We employed a variant of the retrieval-practice paradigm with
      short (20 minutes) and long (12 hours) delay conditions. In all conditions
      participants studied a perceptually categorised list followed by retrieval
      practice on some of the items from some of the categories. Participants studied
      and practised the material in the morning or the evening. RIF was present in the
      short-delay conditions, and it was present in the long-delay condition if the
      delay included nocturnal sleep; if the long delay was filled with diurnal
      wakefulness, RIF was absent. Results show that whether delay eliminates RIF or
      not can depend on whether sleep or wake follows retrieval practice. Connections
      of the results to recent findings about the role of delay and sleep for RIF are
      discussed.

PMID- 22640488
TI  - A two step Bayesian approach for genomic prediction of breeding values.
AB  - BACKGROUND: In genomic models that assign an individual variance to each marker,
      the contribution of one marker to the posterior distribution of the marker
      variance is only one degree of freedom (df), which introduces many variance
      parameters with only little information per variance parameter. A better
      alternative could be to form clusters of markers with similar effects where
      markers in a cluster have a common variance. Therefore, the influence of each
      marker group of size p on the posterior distribution of the marker variances will
      be p df. METHODS: The simulated data from the 15th QTL-MAS workshop were analyzed
      such that SNP markers were ranked based on their effects and markers with similar
      estimated effects were grouped together. In step 1, all markers with minor allele
      frequency more than 0.01 were included in a SNP-BLUP prediction model. In step 2,
      markers were ranked based on their estimated variance on the trait in step 1 and
      each 150 markers were assigned to one group with a common variance. In further
      analyses, subsets of 1500 and 450 markers with largest effects in step 2 were
      kept in the prediction model. RESULTS: Grouping markers outperformed SNP-BLUP
      model in terms of accuracy of predicted breeding values. However, the accuracies
      of predicted breeding values were lower than Bayesian methods with marker
      specific variances. CONCLUSIONS: Grouping markers is less flexible than allowing
      each marker to have a specific marker variance but, by grouping, the power to
      estimate marker variances increases. A prior knowledge of the genetic
      architecture of the trait is necessary for clustering markers and appropriate
      prior parameterization.

PMID- 22640489
TI  - A longitudinal study of processes predicting the specificity of autobiographical
      memory in the adolescent offspring of depressed parents.
AB  - Deficits in specific autobiographical memory retrieval are closely associated
      with depression. The ability to retrieve specific autobiographical memories
      develops throughout childhood and adolescence and is associated with adolescent
      depression within and across time. Studying young samples before they first
      experience depression provides an approach for testing processes that underlie
      reduced autobiographical memory specificity. This study is the first to examine
      the longitudinal association of rumination and executive function with
      autobiographical memory specificity in a sample of adolescents at elevated risk
      for future depression. A total of 259 adolescents (aged between 10 and 18 years)
      completed the Autobiographical Memory Test at baseline and 1-year follow-up.
      Measures of rumination, executive function, and depressive symptoms were obtained
      at baseline. The interaction between rumination and executive function predicted
      autobiographical memory specificity over time. Whereas rumination in the context
      of low executive function predicted reduced specificity, this was not the case in
      the context of high executive function. The interaction between rumination and
      executive function was independent of the effects of age, gender, IQ, baseline
      levels of memory specificity, and depressive symptoms.

PMID- 22640490
TI  - User acceptance of a picture archiving and communication system (PACS) in a Saudi
      Arabian hospital radiology department.
AB  - BACKGROUND: Compared with the increasingly widespread use of picture archiving
      and communication systems (PACSs), knowledge concerning users' acceptance of such
      systems is limited. Knowledge of acceptance is needed given the large (and
      growing) financial investment associated with the implementation of PACSs, and
      because the level of user acceptance influences the degree to which the benefits
      of the systems for healthcare can be realized. METHODS: A Technology Acceptance
      Model (TAM) was used to assess the level of acceptance of the host PACS by staff
      in the radiology department at King Abdulaziz Medical City (KAMC), Riyadh, Saudi
      Arabia. A questionnaire survey of 89 PACS users was employed to obtain data
      regarding user characteristics, perceived usefulness (PU) (6 items), perceived
      ease of use (PEU) (4 items), a change construct (4 items), and a behavior
      (acceptance) construct (9 items). Respondents graded each item in each construct
      using five-point likert scales. RESULTS: Surveyed users reported high levels of
      PU (4.33/5), PEU (4.15/5), change (4.26/5), and acceptance (3.86/5). The three
      constructs of PU, PEU, and change explained 41 % of the variation in PACS user
      acceptance. PU was the most important predictor, explaining 38 % of the variation
      on its own. The most important single item in the explanatory constructs was that
      users found PACS to have improved the quality of their work in providing better
      patient care. Technologists had lower acceptance ratings than did
      clinicians/radiologists, but no influence on acceptance level was found due to
      gender, age, or length of experience using the PACS. Although not directly
      measured, there appeared to be no cultural influence on either the level of
      acceptance or its determinants. CONCLUSIONS: User acceptance must be considered
      when an organization implements a PACS, in order to enhance its successful
      adoption. Health organizations should adopt a PACS that offers all required
      functions and which is likely to generate high PU on the part of its users,
      rather than a system that is easy to use. Training/familiarization programs
      should aim at establishing high levels of PU in all users, particularly
      technologists. Health organizations are advised to measure all the factors that
      influence the acceptance of a PACS by their staff, in order to optimize the
      productivity of the system and realize the potential benefits to the greatest
      extent possible.

PMID- 22640492
TI  - Evaluation of a transient, simultaneous, arbitrary Lagrange-Euler based multi
      physics method for simulating the mitral heart valve.
AB  - A transient multi-physics model of the mitral heart valve has been developed,
      which allows simultaneous calculation of fluid flow and structural deformation. A
      recently developed contact method has been applied to enable simulation of
      systole (the stage when blood pressure is elevated within the heart to pump blood
      to the body). The geometry was simplified to represent the mitral valve within
      the heart walls in two dimensions. Only the mitral valve undergoes deformation. A
      moving arbitrary Lagrange-Euler mesh is used to allow true fluid-structure
      interaction (FSI). The FSI model requires blood flow to induce valve closure by
      inducing strains in the region of 10-20%. Model predictions were found to be
      consistent with existing literature and will undergo further development.

PMID- 22640491
TI  - Exploring flubendazole formulations for use in sheep. Pharmacokinetic evaluation
      of a cyclodextrin-based solution.
AB  - BACKGROUND: Flubendazole (FLBZ) is a poor water solubility broad-spectrum BZD
      methylcarbamate anthelmintic compound. Cyclodextrins (CDs) are usually used to
      increase aqueous solubility of poor hydrosoluble compounds. The comparative in
      vitro aqueous solubility of FLBZ and other BZD anthelmintics in the presence of
      hydroxypropyl-beta-cyclodextrin (HPbetaCD) was evaluated in the current work.
      Additionally, the comparative pharmacokinetic behaviour of FLBZ (and its
      metabolites) administered by the intraruminal (i.r.) or intraabomasal (i.a.)
      routes to sheep as either an aqueous CDs-based solution or a conventional
      carboximethylcellulose (CMC) suspension was assessed. Drug solubility studies
      involving albendazole, mebendazole, oxfendazole and FLBZ were performed in an
      aqueous solution (pH 1.2 or 7.4) with or without HPbetaCD (10%, w/v). The
      pharmacokinetic study involved two experiments. Experiment 1: In a crossover
      study, sheep received either a FLBZ-CDs solution (n = 3) or a FLBZ-CMC suspension
      (n = 3) by the i.r. route (3.8 mg/kg). The treatment Groups were reversed after a
      21-days washout period. Experiment 2: sheep (n = 4) were treated by the i.a.
      route with the FLBZ-CDs solution (3.8 mg/kg). Plasma and abomasal fluid samples
      were collected between 0 and 72 h post-treatment. Samples were analysed by HPLC.
      RESULTS: Improvement of FLBZ aqueous solubility due to CDs resulted markedly
      higher than that observed for mebendazole and albendazole. However, oppositely to
      what was expected, the absorption-related pharmacokinetic parameters did not show
      any marked formulation-dependant effect. After the i.a. administration of FLBZ,
      the AUC and the Tmax of the parent compound were significantly (P < 0.05)
      reduced, which is consistent with ruminal bypass. CONCLUSION: The administration
      of FLBZ as a CDs-based solution, does not seem to achieve great practical
      relevance for parasite control in sheep.

PMID- 22640493
TI  - Survival from in-hospital cardiac arrest on the Internal Medicine clinical
      teaching unit.
AB  - BACKGROUND: There is a paucity of data on patient outcomes following in-hospital
      cardiac arrest (IHCA) on the Internal Medicine clinical teaching unit (CTU).
      Accurate outcome data enhances discussions between patients, surrogates, and
      physicians, and assists in their management. METHODS: We performed a
      retrospective cohort study of consecutive "Code Blue" calls on 2 medical CTUs in
      a Canadian tertiary centre from January 1, 2003 to June 30, 2007. The medical
      records of identified patients were screened for eligibility and patient-specific
      and arrest-specific data were collected for eligible events. Primary outcome was
      survival to hospital discharge. RESULTS: Our cohort comprised 83 patients;
      including 54 (65.1%) men with a mean age of 75 years (range, 38-97). Infection
      (34.9%) was the principal reason for admission and over half of patients had 3 or
      more comorbid illnesses. Forty-three (51.8%) of the IHCA events were witnessed.
      In all, 39 (90.7%) of the witnessed and 36 (90%) of the unwitnessed arrests were
      pulseless electrical activity (PEA) or asystole (P = not significant). Return of
      spontaneous circulation occurred in 29 patients (34.9%) and 2 (2.4%) survived to
      hospital discharge. No patients survived to discharge after unwitnessed arrest.
      CONCLUSIONS: IHCA in Internal Medicine CTU patients is characterized by a high
      rate of PEA/asystole and a minimal chance of survival to hospital discharge.
      Moreover, no patient with an unwitnessed arrest survived to hospital discharge.
      While these findings require confirmation in a larger study, they merit
      consideration in the context of code status discussions, particularly with
      respect to the response to unwitnessed arrests.

PMID- 22640494
TI  - Lifetime risk of cardiovascular disease: the next generation in risk prediction.

PMID- 22640495
TI  - What does anti-Mullerian hormone tell you about ovarian function?
AB  - The measurement anti-Mullerian hormone (AMH) is leading to new insights into
      ovarian function. AMH is produced by small growing follicles, thus is distinct
      from ovulation and is a step closer to being able to assess the true ovarian
      reserve. AMH is measureable from birth to near the menopause, with a peak in the
      mid-20s. Changes in adolescence are likely to lead to new understanding of
      ovarian maturation at puberty. AMH is becoming a routine test in assisted
      conception, reflecting a decline in the primordial follicle pool during the later
      reproductive years, and also identifying women at risk of over-response. Thus,
      its relationship with the ovarian reserve changes from an inverse one in the
      first quarter century to a positive one thereafter as both decline in parallel.
      AMH does not vary significantly across the menstrual cycle, but it is not fully
      gonadotrophin-independent, showing delayed changes consistent with the site of
      production from smaller growing follicles. There is considerable interest, both
      professional and public, in its ability to predict remaining reproductive
      lifespan, which clinically may be of value in the assessment of ovarian reserve
      following damage, for example postchemotherapy or ovarian surgery. AMH is
      markedly increased in polycystic ovarian syndrome and may be of diagnostic value.
      The considerable promise of AMH measurement is ahead of the robustness of the
      data in allowing clinical interpretation in most contexts, but it is clear that
      it will in the future offer novel opportunities for the assessment of ovarian
      function in health as well as disease.

PMID- 22640496
TI  - Impairment in differentiation and cell cycle of thymocytes by loss of a Bcl11b
      tumor suppressor allele that contributes to leukemogenesis.
AB  - Genetic changes in T-ALL are classified into type A abnormalities leading to
      arrest at a specific stage of T-cell differentiation and type B abnormalities
      that target cellular processes including cell cycle regulation. Mutations and
      deletion of a BCL11B haploinsuffiecient tumor suppressor allele have been found
      in 10-16% of T-ALL subgroups. Analysis of Bcl11b(KO/+) mice revealed impaired T
      cell differentiation at two different stages and attenuation of gamma-ray induced
      cell-cycle arrest at S/G2/M phase in immature CD8 single positive cells. Hence,
      those phenotypes provided by loss of a Bcl11b allele favor that Bcl11b mutation
      belongs to type B abnormalities.

PMID- 22640497
TI  - Introduction. CCSVI and its endovascular treatment.

PMID- 22640498
TI  - Chronic cerebrospinal venous insufficiency and multiple sclerosis: history and
      background.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous
      system (CNS) most commonly characterized by focal areas of myelin destruction,
      inflammation and axonal transection. The multicentric inflammation and
      demyelination of the brain and spinal cord are associated with variable
      neurologic symptoms ranging from mild dysfunction to debilitating. Typically,
      these symptoms are marked by episodes of clinical worsening followed by
      improvement. The cause of this disease remains unclear currently, but the
      underlying etiology is generally considered to be immunologically based. Other
      factors, including genetic, environmental and infectious influences have been
      implicated, as well. Now recent studies have proposed that extracranial venous
      obstruction, termed chronic cerebrospinal venous insufficiency (CCSVI) may have a
      role in the pathogenesis of MS or many of its associated clinical manifestations.
      It is postulated that venous narrowing affecting one or more of the jugular veins
      and/or the azygous vein in the chest may be responsible for abnormal blood flow
      in the veins draining the brain and spinal cord. The abnormal flow may initiate
      and/or sustain a local inflammatory response at the blood-brain barrier that
      promote pathological changes within the CNS. This review presents the history of
      the relationship between the vascular system and MS and explores the background
      of basic and clinical investigations that led to the concept of CCSVI.

PMID- 22640499
TI  - Using magnetic resonance imaging as a means to study chronic cerebral spinal
      venous insufficiency in multiple sclerosis patients.
AB  - The goal of this work is to present a broad magnetic resonance imaging (MRI)
      protocol for use in the study of chronic cerebrospinal venous insufficiency
      (CCSVI). The CCSVI MRI protocol includes the following sequences: time-resolved
      contrast-enhanced 3D MR angiography, 2D time-of-flight MR venography, and 3D
      volumetric interpolated breath-hold examination to assess venous structural
      abnormalities; phase-contrast MR imaging at different levels in the neck and
      thoracic cavity to quantify flow through the veins, arteries, and cerebrospinal
      fluid; T2-weighted imaging, T2-weighted fluid-attenuated inversion recovery, and
      pre- and post-contrast T1-weighted imaging of the brain for examinations of
      parenchymal lesions; and finally, susceptibility-weighted imaging for
      quantification of iron deposition in the brain. Data from 111 clinically definite
      multiple sclerosis patients were assessed for potential structural and flow CCSVI
      risk criteria, including stenosis, atresia, aplasia, dominant to subdominant
      venous flow ratio (D:sD), and the sum of their flow rates. Of the 111 patients,
      50 (45%) were determined to be nonstenotic (NST) with no stenosis or atresia in
      their internal jugular veins (IJV), and the rest 61 (55%) were stenotic (ST)
      having at least one internal jugular vein stenosis or atresia. No occurrence of
      aplasia was observed. A D:sD of greater than 3:1 was observed in 15 (24.6%)
      patients of the ST group and 2 (4.0%) patients of the NST group. A sum of
      dominant and subdominant venous flow rate of <8 mL/s was observed in 22 (36.1%)
      patients of the ST group and 6 (12.0%) patients of the NST group. MRI provides
      valuable information in the observation of potential CCSVI risk factors. Low
      total flow in the 2 dominant veins seemed to be the strongest indicator for risk
      of having stenoses in the multiple sclerosis population.

PMID- 22640500
TI  - The use of Doppler ultrasound in the diagnosis of chronic cerebrospinal venous
      insufficiency.
AB  - Chronic cerebrospinal venous insufficiency (CCSVI) may be associated with
      multiple sclerosis, and its treatment has been shown to potentially benefit
      patients with this condition. Color-assisted duplex imaging is used to assess the
      anatomical and physiological parameters of cerebrospinal venous function and to
      diagnose CCSVI. Standardized examination protocols as well as the diagnostic
      criteria used are important elements in ensuring reproducibility of results
      between centers. The objective of this article is to describe the technique our
      laboratory has used to assess patients for the presence of CCSVI using Doppler
      ultrasound.

PMID- 22640501
TI  - Catheter venography and endovascular treatment of chronic cerebrospinal venous
      insufficiency.
AB  - Multiple sclerosis (MS) is a disorder characterized by damage to the myelin
      sheath insulation of nerve cells of the brain and spinal cord affecting nerve
      impulses which can lead to numerous physical and cognitive disabilities. The
      disease, which affects over 500,000 people in the United States alone, is widely
      believed to be an autoimmune condition potentially triggered by an antecedant
      event such as a viral infection, environmental factors, a genetic defect or a
      combination of each. Chronic cerebrospinal venous insufficiency (CCSVI) is a
      condition characterized by abnormal venous drainage from the central nervous
      system that has been theorized to have a possible role in the pathogenesis and
      symptomatology of MS (1). A significant amount of attention has been given to
      this theory as a possible explanation for the etiology of symptoms related to MS
      patients suffering from this disease. The work of Dr. Zamboni, et al, who
      reported that treating the venous stenoses causing CCSVI with angioplasty
      resulting in significant improvement in the symptoms and quality of life of
      patients with MS (2) has led to further interest in this theory and potential
      treatment. The article presented describes endovascular techniques employed to
      diagnose and treat patients with MS and CCSVI.

PMID- 22640502
TI  - Intravascular ultrasound in the diagnosis and treatment of chronic cerebrospinal
      venous insufficiency.
AB  - Multiple imaging modalities have been used for the evaluation of chronic
      cerebrospinal venous insufficiency (CCSVI). These include Doppler ultrasound,
      magnetic resonance venography, computed tomographic venography, and catheter
      venography. Although each of these tests is considered to contribute valuable
      information to the evaluation, each modality has deficiencies, which can impact
      treatment. Intravascular ultrasound (IVUS) has a role in this evaluation owing to
      its ability to accurately assess vessel circumference and cross-sectional area in
      real time. This can aid in identifying significant stenoses and optimizing
      balloon sizing during angioplasty. In addition, intraluminal abnormalities that
      may be difficult to see with venography can be identified with IVUS, which can
      further determine when angioplasty for CCSVI is indicated. Finally, IVUS can
      identify potential complications of angioplasty, including dissection and
      thrombus formation, allowing for rapid treatment. As a result, IVUS is an
      important part of an evaluation for CCSVI and, when available, should be used to
      identify patients who may benefit from endovascular treatment.

PMID- 22640503
TI  - Reported outcomes after the endovascular treatment of chronic cerebrospinal
      venous insufficiency.
AB  - Chronic cerebrospinal venous insufficiency (CCSVI) has recently been implicated
      as a potential causal factor in the development of multiple sclerosis (MS). The
      treatment of jugular and azygous vein stenoses, characteristic of CCSVI, has been
      proposed as a potential component of therapy for MS. In the few short years since
      Dr. Paulo Zamboni published "A Prospective Open label Study of Endovascular
      Treatment of Chronic Cerebrospinal Venous Insufficiency", there has been
      tremendous patient-driven demand for treatment. Concurrently, there have been
      numerous publications since 2009 addressing CCSVI and its association with MS.
      The purpose of this article is to present a brief review of CCSVI and its
      association with MS and to review the available literature to date with a focus
      on outcomes data.

PMID- 22640504
TI  - Placebo power.
AB  - A variable placebo response has been previously described in the multiple
      sclerosis (MS) literature and in sham surgical trials involving other patient
      populations. Conditioning and expectancy models are proposed to explain the
      biological mechanisms of a placebo response. Possibly, when neuroimmune
      mechanisms are involved in the disease process, placebo and treatment responses
      interact. The measurement of a placebo response related to endovascular
      procedures in MS may be scientifically and ethically challenging. Based on the
      factors associated with larger placebo responses, it is estimated that a
      significant placebo response may be associated with these procedures. The factors
      and mechanisms associated with marked placebo responses should be considered in
      the design of future studies related to the investigation of endovascular
      procedures for MS.

PMID- 22640505
TI  - Internet-based social networking and its role in the evolution of chronic
      cerebrospinal venous insufficiency.
AB  - The Internet is being seen as a growing resource for health-related information
      for a large number of patients. It is undeniable that its widespread presence has
      led to the growth of awareness that chronic cerebrospinal venous insufficiency
      (CCSVI) as an entity that may contribute to the symptoms experienced by patients
      with multiple sclerosis (MS). Social networking and file-sharing Web sites have
      brought patients with MS together from all over the world and have facilitated
      the distribution of personal experiences and information derived from medical
      research as it relates to CCSVI. As a result, there has been an accelerated
      growth in the number of patients seeking treatment for this syndrome in light of
      the possibility that it may improve their present condition. This article will
      review this phenomenon, the Internet-based resources available to MS patients
      seeking information about CCSVI, and the responsibilities of physicians as they
      participate in these online discussions.

PMID- 22640506
TI  - Psychosocial stressors and the prognosis of major depression: a test of Axis IV.
AB  - BACKGROUND: Axis IV is for reporting 'psychosocial and environmental problems
      that may affect the diagnosis, treatment and prognosis of mental disorders'. No
      studies have examined the prognostic value of Axis IV in DSM-IV. METHOD: We
      analyzed data from 2497 participants in the National Epidemiologic Survey on
      Alcohol and Related Conditions (NESARC) with major depressive episode (MDE). We
      hypothesized that psychosocial stressors predict a poor prognosis of MDE.
      Secondarily, we hypothesized that psychosocial stressors predict a poor prognosis
      of anxiety and substance use disorders. Stressors were defined according to DSM
      IV's taxonomy, and empirically using latent class analysis (LCA). RESULTS:
      Primary support group problems, occupational problems and childhood adversity
      increased the risks of depressive episodes and suicidal ideation by 20-30%.
      Associations of the empirically derived classes of stressors with depression were
      larger in magnitude. Economic stressors conferred a 1.5-fold increase in risk for
      a depressive episode [95% confidence interval (CI) 1.2-1.9]; financial and
      interpersonal instability conferred a 1.3-fold increased risk of recurrent
      depression (95% CI 1.1-1.6). These two classes of stressors also predicted the
      recurrence of anxiety and substance use disorders. Stressors were not related to
      suicidal ideation independent from depression severity. CONCLUSIONS: Psychosocial
      and environmental problems are associated with the prognosis of MDE and other
      Axis I disorders. Although DSM-IV's taxonomy of stressors stands to be improved,
      these results provide empirical support for the prognostic value of Axis IV.
      Future work is needed to determine the reliability of Axis IV assessments in
      clinical practice, and the usefulness of this information to improving the
      clinical course of mental disorders.

PMID- 22640507
TI  - Important research, but did the participants consent?

PMID- 22640508
TI  - The right to autonomy under operational research: should we reflect the spirit
      rather than letter of ethical guidelines?

PMID- 22640509
TI  - Lung cancer among non-smokers.

PMID- 22640510
TI  - Community-based multi-disease prevention campaigns for controlling human
      immunodeficiency virus-associated tuberculosis.
AB  - Human immunodeficiency virus (HIV) infection increases the risk of tuberculosis
      (TB) 21-34 fold, and has fuelled the resurgence of TB in sub-Saharan Africa. The
      World Health Organization (WHO) recommends the Three I's for HIV/TB (infection
      control, intensified case finding [ICF]  and isoniazid preventive therapy) and
      earlier initiation of antiretroviral therapy for preventing TB in persons with
      HIV. Current service delivery frameworks do not identify people early enough to
      maximally harness the preventive benefits of these interventions. Community-based
      campaigns were  essential components of global efforts to control major public
      health threats such as polio, measles, guinea worm disease and smallpox. They
      were also successful in helping to control TB in resource-rich settings. There
      have been recent community-based efforts to identify persons who have  TB and/or
      HIV. Multi-disease community-based frameworks have been rare. Based on findings
      from a WHO meta-analysis and a Cochrane review, integrating ICF into the recent
      multi-disease prevention campaign in Kenya may have had implications in
      controlling TB. Community-based multi-disease prevention  campaigns represent a
      potentially powerful strategy to deliver prevention interventions, identify
      people with HIV and/or TB, and link those eligible to care and treatment.

PMID- 22640511
TI  - Extension of the intensive phase reduces relapse but not failure in a regimen
      with rifampicin throughout.
AB  - SETTING: Damien Foundation tuberculosis (TB) control projects in Bangladesh.
      OBJECTIVE: To assess the effectiveness of extending the intensive phase (P1) of
      treatment by 1 month for patients who are smear-positive after 2 months of a 6
      month regimen containing rifampicin (RMP) throughout. DESIGN: Prospective
      operational study randomising P1 extension for new smear-positive cases with any
      number of acid-fast bacilli in the 2-month smear (2M+). Smear-defined failures
      and relapses underwent culture and drug susceptibility testing in addition to DNA
      sequencing of the rpoB gene before and after treatment. RESULTS: Of 16,708
      patients evaluated, 12,967 were smear-negative at 2 months (2M-); 1871 and 1870
      2M+ were randomised to no extension or extension. Respectively 0.3% (95%CI 0.2
      0.4), 1.2% (95%CI 0.7-1.8) and 2.0% (95%CI 1.4-2.8) smear- and culture-positive
      failures, and 1.2% (95%CI 1.0-1.4), 2.6% (95%CI 1.9-3.4) and 0.9% (95%CI 0.5-1.4)
      relapses were detected. Extension significantly reversed the relative risk (RR)
      of relapse of 2M+ vs. 2M- patients from 2.2 (95%CI 1.6-3.0) to 0.7 (95%CI 0.4
      1.2). The RR for failure remained high, at 7.3 (95%CI 4.7-11.5) with and 4.2
      (95%CI 2.5-7.2) without extension. More multi-drug resistance was found after
      extension, but acquired RMP resistance was similar in all arms. The fair
      sensitivity of the 2-month smear for failure or relapse (40%) was offset by a
      very low positive predictive value (3%). CONCLUSIONS: Extension of P1 is very
      inefficient with this 6-month regimen. Operational research should define
      appropriate algorithms allowing an earlier switch to the next higher regimen for
      those in need, using follow-up smears for screening.

PMID- 22640512
TI  - Increasing directly observed therapy related to improved tuberculosis treatment
      outcomes in Taiwan.
AB  - SETTING: Directly observed therapy (DOT) is a core element of tuberculosis (TB)
      care and control efforts. In Taiwan, DOT was implemented in 2006, when the Stop
      TB Strategy was adopted as a national policy. OBJECTIVE: To quantify DOT among
      patients on anti-tuberculosis treatment and measure the association between
      proportion of DOT and TB treatment outcomes at a national level in Taiwan.
      DESIGN: We analyzed data prospectively collected on all new pulmonary TB cases
      reported to the national web-based registry between 1 January 2007 and 30 June
      2008. We compared treatment outcomes and proportion of DOT in multivariable
      analyses. RESULTS: Among 11,528 patients initiating anti-tuberculosis treatment,
      the proportion of days during which an official DOT observer witnessed treatment
      was >60% for 5150 (45%) patients and <=60% for 4601 (40%) patients, whereas for
      1777 (15%) patients no days of DOT were recorded. Being older, male, having
      positive bacteriology results and a non-World Health Organization recommended
      treatment regimen at baseline were independently related to unsuccessful
      treatment outcomes and mortality. A dose-response effect was found between
      proportion of DOT and these outcomes. CONCLUSION: These findings highlight the
      importance of ensuring universal DOT in improving treatment outcomes among new
      pulmonary TB patients.

PMID- 22640513
TI  - Reasons for non-participation in an international multicenter trial of a new drug
      for tuberculosis treatment.
AB  - SETTING: Clinical trials can provide a high standard of patient care and
      contribute to scientific knowledge; however, only a fraction of the patients
      screened participate and receive treatment as part of a trial. OBJECTIVE: To
      explore reasons why patients were not enrolled in an  international tuberculosis
      (TB) treatment trial and to compare experiences among study sites. DESIGN: An
      analysis of reasons why patients were not enrolled was conducted among patients
      screened for a TB clinical trial at 26 sites in North and South America, Africa,
      and Europe. RESULTS: Staff at study sites screened 1119 potential candidates for
      the trial: 61% (n = 686) were not enrolled due to 1) failure to meet eligibility
      criteria (n = 405, 59%), 2) site's decision (n = 168, 24%), or 3) candidate's
      choice (n = 113, 16%). Study staff recorded  a total of 144 reasons for why they
      believed patients chose not to participate, including concerns over research
      (28%), conflicts with work or school (21%), and lifestyle and family issues
      (20%). Socio-demographic and geographic factors also influenced participation.
      CONCLUSION: Increased  evaluation of screening outcomes and of specific
      interventions, such as improved education and communication about trial
      procedures, may increase the efficiency of screening and enrollment in clinical
      trials.

PMID- 22640514
TI  - Association of streptomycin resistance mutations with level of drug resistance
      and Mycobacterium tuberculosis genotypes.
AB  - OBJECTIVES: To determine 1) the relationship between specific streptomycin (SM)
      resistance mutations and the minimum inhibitory concentration (MIC), and 2)
      whether these mutations are preferentially associated with the Beijing genotype
      in Viet Nam. METHODS: A total of 131 consecutive  Mycobacterium tuberculosis
      isolates resistant to either isoniazid (INH) or rifampicin (RMP), collected
      previously, were tested for SM resistance, spoligotyped and sequenced in the
      rpsL, rrs and gidB genes. The MIC for 50 mutants was also determined. RESULTS:
      Overall, 116/131 isolates were SM-resistant. The three most frequently occurring
      mutation sites in rpsL and rrs were at codon 43 of rpsL (72/116, 62.1%), rpsL88
      (22/116, 18.9%) and rrs514 (8/116, 6.9%). Mutations in the rrs910 region were
      found in  two isolates (1.7%), and three isolates had mutations in both rpsL and
      rrs (2.6%). gidB mutations were found in both resistant and susceptible strains.
      Among SM-resistant isolates resistant to INH/RMP, the Beijing genotype was
      strongly associated with rpsL43 mutation  (aOR 23.6, 95%CI 2.9-193.4, P = 0.002).
      The median MIC for each mutation was as follows: rpsL43 = 256 MUg/ml, rpsL88 = 16
      MUg/ml, 515 loop = 4 MUg/ml, 910 region = 8 MUg/ml, and double mutation = 256
      MUg/ml. We found a strong association between rpsL43 and high drug resistance
      levels, with all rpsL43 mutants having an MIC >256 MUg/ml (P < 0.001).

PMID- 22640515
TI  - Tuberculosis infection in the indigenous elderly White UK population: a study of
      IGRAs.

PMID- 22640516
TI  - The need for building design professionals in operational research in low-income
      countries.

PMID- 22640518
TI  - Completion of isoniazid preventive therapy and survival in HIV-infected TST
      positive adults in Tanzania.

PMID- 22640519
TI  - Isoniazid preventive therapy in human immunodeficiency virus infection.

PMID- 22640521
TI  - The role of cytokinin during Arabidopsis gynoecia and fruit morphogenesis and
      patterning.
AB  - Cytokinins have many essential roles in embryonic and post-embryonic growth and
      development, but their role in fruit morphogenesis is currently not really known.
      Moreover, information about the spatio-temporal localization pattern of cytokinin
      signaling in gynoecia and fruits is lacking. Therefore, the synthetic reporter
      line TCS::GFP was used to visualize cytokinin signaling during gynoecium and
      fruit development. Fluorescence was detected at medial regions of developing
      gynoecia, and, unexpectedly, at the valve margin in developing fruits, and was
      severely altered in mutants that lack or ectopically acquire valve margin
      identity. Comparison to developing gynoecia and fruits in a DR5rev::GFP line
      showed that the transcriptional responses to cytokinin and auxin are frequently
      present in complementary patterns. Moreover, cytokinin treatments in early
      gynoecia produced conspicuous changes, and treatment of valve margin mutant
      fruits restored this tissue. The results suggest that the phytohormone cytokinin
      is important in gynoecium and fruit patterning and morphogenesis, playing at
      least two roles: an early proliferation-inducing role at the medial tissues of
      the developing gynoecia, and a late role in fruit patterning and morphogenesis at
      the valve margin of developing fruits.

PMID- 22640522
TI  - Workshop on immunotherapy combinations. Society for Immunotherapy of Cancer
      annual meeting Bethesda, November 3, 2011.
AB  - Although recent FDA approvals on ipilimumab and sipuleucel-T represent major
      milestones, the ultimate success of immunotherapy approaches will likely benefit
      from appropriate combinations with other immunotherapeutic and/or non
      immunotherapeutic approaches. However, implementation of ideal combinations in
      the clinic may still face formidable challenges in regulatory, drug-availability
      and intellectual property aspects. The 2011 SITC annual meeting hosted a workshop
      on combination immunotherapy to discuss: 1) the most promising combinations found
      in the laboratory; 2) early success of combination immunotherapy in clinical
      trials; 3) industry perspectives on combination approaches, and 4) relevant
      regulatory issues. The integrated theme was how to accelerate the implementation
      of efficacious combined immunotherapies for cancer patients. Rodent animal models
      are providing many examples of synergistic combinations that typically include
      more than two agents. However, mouse and human immunology differ in a significant
      number of mechanisms and hence we might be missing opportunities peculiar to
      humans. Nonetheless, incisive animal experimentation with deep mechanistic
      insight remains the best compass that we can use to guide our paths in
      combinatorial immunotherapy. Combination immunotherapy clinical trials are
      already in progress and preliminary results are extremely promising. As a key to
      translate promising combinations into clinic, real and "perceived" business and
      regulatory hurdles were debated. A formidable step forward would be to be able to
      test combinations of investigational agents prior to individual approval. Taking
      together the FDA and the industrial perspective on combinatorial immunotherapy,
      the audience was left with the clear message that this is by no means an
      impossible task. The general perception is that the road ahead of us is full of
      combination clinical trials which hopefully will bring clinical benefit to our
      cancer patients at a fast pace.

PMID- 22640523
TI  - Comment on 'Levels of soluble endothelial selectin in umbilical cord serum are
      influenced by gestational age and histological chorioamnionitis, but not by pre
      eclampsia'.

PMID- 22640524
TI  - Diode laser endoscopic cyclophotocoagulation in the normal equine eye.
AB  - OBJECTIVE: To determine the clinical and histologic effects of diode endoscopic
      cyclophotocoagulation (ECP) in the phakic equine eye. ANIMALS STUDIED: Phase I:
      10 equine cadaver eyes. Phase II: four normal adult horses. PROCEDURES: Phase I:
      ECP probe angle of reach (AR) was determined. Multiple ECP energy levels: 0.75,
      0.90, 1.05, 1.20, 1.35, 1.50 J, and the resulting visible and histologic ciliary
      process changes were evaluated. Phase II: Ocular quadrants were treated with ECP
      at 0.90, 1.14, 1.38 J, and a control. The contralateral eye underwent a sham
      operation. Tissue changes (clinical and histologic) were evaluated. RESULTS:
      Phase I: Mean combined AR was 162 +/- 29 degrees. Mean visible tissue scores:
      2.60 +/- 0.58 (0.75 J) to 5.04 +/- 0.30 (1.50 J) from possible total of 6. Tissue
      'popping' was observed at 1.50 J. Histologic ciliary tissue damage was present at
      all settings. Phase II: Mean visible tissue scores: 2.90 +/- 0.48 (0.90 J), 3.61
      +/- 0.57 (1.14 J), and 4.52 +/- 0.56 (1.38 J). Tissue 'popping' was observed at
      1.38 J. Histologic ciliary tissue damage was present at all settings. Clinical
      effects included acute inflammation, intraocular pressure reduction, cataract
      formation, corneal edema, corneal ulceration, and postoperative ocular
      hypertension. CONCLUSIONS: Diode ECP between 0.90 and 1.14 J is a potential
      treatment option for glaucoma in horses based on visible tissue effects and
      target ciliary epithelium damage. Iatrogenic cataract development may limit the
      use of an anterior chamber approach in phakic horses. Supported in part by an
      ACVO VAF grant.

PMID- 22640525
TI  - Effect of estrogen therapy on vascular perlecan and metalloproteinases 2 and 9 in
      castrated rats.
AB  - AIM: To study the effects of estrogen therapy on the expression of matrix
      metalloproteinases 2 and 9 (MMP-2 and MMP-9) and perlecan in the vascular wall.
      METHODS: Twenty 180-day-old Wistar rats were castrated and treated 1 week later
      for a period of 4 weeks with one of the following: (1) placebo; (2) 0.5 MUg/day
      estradiol benzoate (E(2)B); (3) 5 MUg/day E(2)B; (4) 50 MUg/day E(2)B. A fifth
      group consisted of rats that had not been castrated. Following treatment,
      expression of MMP-2 and MMP-9 mRNA (MMP-2([RNA]) and MMP-9([RNA]), respectively)
      was analyzed by real-time PCR, and expression of MMP-2 (MMP-2([IH])), MMP-9 (MMP
      9([IH])) and perlecan was quantified by immunohistochemistry, in carotid walls.
      RESULTS: There were no differences among castrated groups for MMP-2([RNA]) (p =
      0.1969) and for MMP-9([RNA]) (p = 0.1828); however, a correlation was observed
      between E(2)B dose and MMP-9([RNA]) levels (r = 0.471, p = 0.018). Differences
      among groups were observed for MMP-2([IH]), MMP-9([IH]) and perlecan (p <
      0.0001), wherein higher levels were observed in animals treated with estrogen
      therapy, correlating with E(2)B doses in the case of MMP-9 (r = 0.441, p = 0.026)
      and perlecan (r = 0.574, p = 0.005). CONCLUSIONS: Estrogen therapy correlates
      with higher levels of MMP-2, MMP-9 and perlecan in the extracellular matrix of
      carotid walls in castrated rats, in a dose-dependent manner. There was a dose
      response effect of E(2)B on the expression of MMP-9 mRNA and, possibly, MMP-2
      mRNA.

PMID- 22640526
TI  - Arthroscopic-assisted removal of proximal tibia locking plates.
AB  - We present a new technique to remove plates from the proximal tibia arthroscopic
      assisted with all advantages of the minimally invasive surgery and the
      possibility to treat concomitant intraarticular pathologies. The initial results
      (n = 7) are promising with an increase of the Lysholm score in all cases studied
      [preop. median 78 (range 32-100), postop. median 89 (range 60-100)]. In
      conclusion, arthroscopic-assisted hardware removal at the proximal tibia is
      feasible and may provide patients with all the benefits of minimal-invasive
      hardware removal. The described technique can be recommended for all surgeons
      familiar with arthroscopic surgery.

PMID- 22640527
TI  - The distribution of large herbivore hotspots in relation to environmental and
      anthropogenic correlates in the Mara region of Kenya.
AB  - 1. The distributions of large herbivores in protected areas and their
      surroundings are becoming increasingly restricted by changing land use, with
      adverse consequences for wildlife populations. 2. We analyse changes in
      distributions of herbivore hotspots to understand their environmental and
      anthropogenic correlates using 50 aerial surveys conducted at a spatial
      resolution of 5 * 5 km(2) (n = 289 cells) in the Mara region of Kenya during 1977
      2010. We compare the distributions across seasons, land use types (protection,
      pastoralism and agro-pastoralism) and 10 species with different body sizes and
      feeding styles. 3. Small herbivores that are the most susceptible to predation
      and dependent on high-quality forage concentrate in the greenest and wet areas
      and close to rivers in Masai pastoral ranches in both seasons. Livestock grazing
      creates conditions favouring small herbivores in these ranches, including high
      quality short grasses and better visibility, implying facilitation. But in the
      reserve, they concentrate in browner, drier and flatter areas and farther from
      rivers, suggesting facilitation by large grazers in the wet season, or little
      competition with migratory herbivores occupying the reserve in the dry season. 4.
      In the wet season, medium herbivores concentrate in similar areas to small
      herbivores in the ranches and reserve. However, in the dry season, they stay in
      the reserve, and also concentrate in green and wet areas close to rivers when
      migrants occur in the reserve. As such areas typically have higher predation
      risk, this suggests facilitation by the migrants by absorbing most predation
      pressure or, alternatively, competitive displacement by the migrants from
      preferred habitats. 5. Large herbivores, which suffer the least predation, depend
      on bulk forage and are the most likely to engender conflicts with people,
      concentrate in the reserve all year. This suggests attraction to the taller and
      denser grass and perceived greater safety in the reserve in both seasons. 6.
      These results reveal how predation risk, forage quantity and quality, water,
      competition with and facilitation by livestock interact with individual life
      history traits, seasons and land use in shaping the dynamics of herbivore
      hotspots in protected and human-dominated savannas.

PMID- 22640528
TI  - Self-neglect of the elderly. An overview.
AB  - Self-neglect is characterized by the inability to perform essential self-care
      tasks threatening a person's health and safety. The exact prevalence of self
      neglect in a community-based aged population is not known. Cognitive impairment
      is the most important predisposing factor of self-neglect. There are also a
      number of other predisposing factors such as psychiatric diseases, pre-morbid
      personality, alcohol abuse, poor physical ability, lack of social support and a
      low socioeconomic situation. Self-neglect has a number of serious consequences.
      It is an independent risk factor for early mortality among the aged. It commonly
      causes malnutrition, frailty and the deterioration of physical ability,
      therefore, increasing the risk of falls and fractures. Untreated medical
      conditions result in emergency visits and acute hospitalization. The neglect of
      housekeeping and financial affairs seriously affects the domestic environment.
      Diagnosis and treatment of self-neglect should be based on the medical and
      psychosocial assessment of a patient. Patients require multidisciplinary support
      at home or in hospital, and sometimes long-term care is inevitable. There is no
      sufficient scientific evidence to support the benefits of early intervention in
      self-neglect. Controlled studies are needed, especially to show whether early
      diagnosis followed by increased social support and tailored health care services
      have an effect on the outcome.

PMID- 22640529
TI  - Obesity, family instability, and socioemotional health in adolescence.
AB  - The last two decades have witnessed dramatic increases in obesity and family
      instability. To the extent that the social stigma of obesity is a risk factor and
      family instability represents the potential compromise of important protective
      factors, their convergence may disrupt socioemotional health, especially during
      periods of heightened social uncertainty. Drawing on data from the National
      Longitudinal Study of Adolescent Health, this study found that obese youth at the
      start of high school had higher levels of internalizing symptoms and lower levels
      of perceived social integration in school only when they had also experienced
      multiple family transitions since birth. This pattern, however, did not hold for
      boys, and it did not extend to overweight (as opposed to obese) adolescents of
      either gender.

PMID- 22640530
TI  - Within-family variation in obesity.
AB  - We use data from the Children of the National Longitudinal Survey of Youth 1979
      to document the degree to which childhood obesity varies among siblings. We find
      considerable differences in body weight between siblings with over half of the
      siblings differing by more than 20 age-specific percentiles in terms of the body
      mass index. Even among identical twins, there is an average BMI difference of 12
      percentiles. This variation is important for the use of econometric approaches
      that involve sibling comparisons.

PMID- 22640532
TI  - Predictive factors of in-hospital mortality in colon and rectal surgery.
AB  - BACKGROUND: Knowledge of the independent risk factors for mortality in colon and
      rectal surgery can aid surgeons in surgical decision making and in providing
      patients with appropriate information about the risks of surgery. This study
      endeavors to identify the risk factors for mortality that are associated with
      colon and rectal surgery. STUDY DESIGN: Using the Nationwide Inpatient Sample
      database, we examined the clinical data of patients who underwent colon and
      rectal resection from 2006 to 2008. Multivariate regression analysis was
      performed to identify factors predictive of in-hospital mortality. RESULTS: A
      total of 975,825 patients underwent colon and rectal resection during this
      period. Overall, the rate of in-hospital mortality was 4.50% (elective surgery,
      1.42% vs emergent surgery, 8.76%; p < 0.01). Mortality was lower after
      laparoscopic compared with open operation (1.43% vs 4.74%; p < 0.01). Using
      multivariate regression analysis, significant risk factors for in-hospital
      mortality were emergent surgery (adjusted odds ratio [AOR] = 3.53), liver disease
      (AOR = 3.02), age older than 65 years (AOR = 2.92), total colectomy (AOR = 2.88),
      chronic renal failure (AOR = 2.37), malignant tumor (AOR = 2.0), open operation
      (AOR = 1.85), peripheral vascular disease (AOR = 1.81), diverticulitis (AOR =
      1.77), transverse colectomy (AOR = 1.43), chronic lung disease (AOR = 1.41),
      ulcerative colitis (AOR = 1.40), left colectomy (AOR = 1.31), alcohol abuse (AOR
      = 1.21), male sex (AOR = 1.12), nonteaching hospital (AOR = 1.11), and African
      American race (AOR = 1.09). There was no association between hypertension,
      diabetes, congestive heart failure, obesity, smoking, proctectomy, sigmoidectomy,
      or Crohn disease and in-hospital mortality. CONCLUSIONS: In patients undergoing
      colorectal surgery, emergent surgery, liver disease, total colectomy, age older
      than 65 years, chronic renal failure, and malignant tumor are the major risk
      factors for in-hospital mortality.

PMID- 22640533
TI  - Investigating embryo deaths and hatching failure.
AB  - Investigation of all embryo and neonatal mortalities is essential for optimizing
      productivity in artificial incubation and hand rearing programs. Because
      artificial incubation is a complex process with many variables, thorough and
      systematic evaluations are necessary to identify potential problems. Every step
      of the process from egg lay through incubation and hatching should be evaluated
      in conjunction with comprehensive data on management of the breeding population.
      The most common sources of significant problems include nutrition and management
      of the breeding population, insufficient parental incubation prior to artificial
      incubation, abnormal egg weight loss during incubation, and infections of the
      yolk sac or umbilicus.

PMID- 22640531
TI  - The impact of care pathways for patients with proximal femur fracture: rationale
      and design of a cluster-randomized controlled trial.
AB  - BACKGROUND: Proximal femur fracture (PFF) is associated with considerable
      morbidity and mortality. The European Quality of Care Pathway (EQCP) study on PFF
      (NCT00962910) was designed to determine how care pathways (CP) for hospital
      treatment of PFF affect consistency of care, adherence to evidence-based key
      interventions, and clinical outcome. METHODS/DESIGN: An international cluster
      randomized controlled trial (cRCT) will be performed in Belgium, Ireland, Italy
      and Portugal. Based on power analyses, a sample of 44 hospital teams and 437
      patients per arm will be included in the study. In the control arm, usual care
      will be provided. Experimental teams will implement a care pathway which will
      include three active components: a formative evaluation of quality and
      organization of the care setting, a set of evidence-based key interventions, and
      support of the development and implementation of the CP. Main outcome will be the
      six-month mortality rate. DISCUSSION: The EQCP study constitutes the first
      international cRCT on care pathways. The EQCP project was designed as both a
      research and a quality improvement project and will provide a real-world
      framework for process evaluation to improve our understanding of why and when CP
      can really work. TRIAL REGISTRATION NUMBER: NCT00962910.

PMID- 22640534
TI  - Psittacine incubation and pediatrics.
AB  - Psittacine pediatric medicine and surgery can only continue to be practiced by
      avian veterinarians if psittacine aviculture (the successful captive breeding of
      parrot species) is active and thriving. Although beautiful, intelligent parrots
      are popular as beloved pets and reside in zoo and private collections around the
      world, private psittacine aviculture is in a transition period recovering from
      difficult economic times. Many of the larger aviculturists have left and the rise
      of the small aviculturist has significantly changed the industry.

PMID- 22640535
TI  - Toucan hand feeding and nestling growth.
AB  - A retrospective analysis of hand-feeding records and growth data from 3
      facilities was performed to determine the growth pattern for 8 toucan species
      raised in captivity. General philosophies of breeding and rearing were similar
      but approaches to hand-feeding varied. General hand-feeding and chick management
      records from hatch to fledging were reviewed for 2 of the 3 facilities. Effective
      hand-feeding formulas were commercially available and minimally modified. Growth
      curves were developed. Curves approximated typical expected patterns of nestling
      growth with no loss of weight at fledging. This study provides a basis for hand
      feeding protocols and growth curves to assess development.

PMID- 22640536
TI  - General principles of nutrition for the newly hatched chick.
AB  - Nutrition of the newly hatched chick is complex and requires an understanding of
      the wild-type feeding strategy of the species, the known nutrient requirements of
      birds, and appropriate application to the species in question. Next, composition
      of available food items, appropriate physical form, volume and frequency of food
      items, and desired end results (eg, appropriate fledging weight, ability to
      successfully find prey items or be socialized for human interactions, etc) need
      to be considered to provide the highest chance of successful fledging. There are
      several excellent resources to help guide the practical aspects of rearing chicks
      (eg, Gage and Duerr), in addition to nutritional resources to guide a better
      understanding of the fundamentals of avian nutrition (eg, Klasing).

PMID- 22640537
TI  - Are there long-term effects of production-based rearing on pet bird behavior?
AB  - The pet industry has long been attuned to keeping a ready supply of animals for
      public purchase. In the years prior to 1970, the majority of larger psittacine
      birds available for sale to the public were imported animals that were caught as
      young adults or nestlings from nests. As concern for the effect of this type of
      trade on native populations became publicized, many collected these imported
      species and set up pairs to breed parrots to fill this need domestically.
      Ultimately, this may result in a poor experience that results in unhappiness and
      one less pet owner as a client for the entire industry.

PMID- 22640538
TI  - Cassowary pediatrics.
AB  - Abduction at the stifle joint is a common deformity upon hatching often referred
      to as splay leg. One possible cause hypothesized is larger yolk sacs force apart
      the cassowary chick's legs (see Fig. 17). Splay leg is most common in the first 2
      or 3 chicks of the season. Usually 1 leg is affected but both can be involved.
      Treatment is generally successful with bandaging techniques. This is done by
      hobbling with bandage tape. (above the hock) for 3 days and observing closely for
      correct alignment.

PMID- 22640539
TI  - Nondomestic avian pediatric pathology.
AB  - This is a snapshot of avian neonatal pathology-not an exhaustive review. Through
      knowledge and recognition of the significant pathogenic challenges of avian
      neonates and the associated lesions, avian practitioners can improve their
      diagnostic and therapeutic success. An area of need for avian research is
      determining the specific pathogenesis of many conditions affecting avian
      neonates. By narrowing the specific etiologies, we can improve management and
      reduce neonatal concerns.

PMID- 22640540
TI  - Reptilian and amphibian pediatric medicine and surgery.
AB  - Herpetological medicine and surgery requires knowledge and understanding of many
      different species. Herpetological pediatrics requires even more knowledge and
      understanding of the differences between adult and neonate, juvenile, and
      subadult patients. Proper environmental conditions and diet are critical to the
      health of growing reptiles, and providing the proper conditions and care for
      hospitalized patients is a vital component of treatment. Challenges often exist
      due to patient size. Exams, diagnostics, treatments, and surgeries can all be
      performed successfully on most pediatric patients. Flexibility in thought
      processes and techniques, the ability to adjust to the specific needs of each
      case, and some special small or fine equipment enable veterinarians to provide
      high-quality veterinary care to pediatric patients.

PMID- 22640541
TI  - Approaches to management and care of the neonatal nondomestic ruminant.
AB  - Management and care of the nondomestic ruminant neonate are similar in principle
      to domestic animal practice. Housing of the dam, conditions for birth,
      preparation for intervention, and plans for treatment and hand-rearing of sick
      neonates must all be considered carefully before undertaking nondomestic ruminant
      breeding. Unfortunately, neonatal losses tend to be much higher in nondomestic
      calves before weaning than in domestic cattle, sheep, and goat herds.1 With
      continued habitat and population declines in wild species, successful captive
      breeding of nondomestic herds becomes more important to species sustainability
      and potential reintroduction programs. The primary challenges contributing to
      neonatal losses in nondomestic ruminants are often animal temperament and
      adaptation to captivity. Only through experience can some of these challenges be
      overcome. However, by understanding some species-specific behavioral tendencies
      and the fractious nature of nondomestic ruminants in general, we can improve our
      success in managing and maintaining healthy populations of nondomestic ruminants
      in captivity.

PMID- 22640542
TI  - Veterinary pediatrics of butterflies, moths, and other invertebrates.
AB  - In the life cycle of invertebrate animals, the typical life history includes the
      egg and larval stage, which may be called the pediatric phases, representing
      development up to the point where the animal reaches adulthood with fully
      functional reproductive organs and full adult characteristics of morphology,
      coloration, physiology, and behavior. These typical immature or pediatric stages
      are found in both terrestrial and aquatic invertebrates. This article reviews the
      factors that impact the health and survival of juvenile stages of butterflies and
      moths in particular, and what can be done to extend veterinarian care and advice
      to clients to invertebrate problems.

PMID- 22640543
TI  - Basics of macaque pediatrics.
AB  - It is clear that raising infants with their mothers and family group is ideal for
      their appropriate development. When this is not feasible, it is necessary to try
      to detect abnormalities beforehand and avoid circumstances that can be
      detrimental to the animal's social and reproductive behavior. It is of great
      importance to try to simulate as much as possible an environment adequate enough
      to develop a species-specific behavior. Multiple measurements and parameters
      exist to evaluate macaque infants. Although infants are vulnerable to multiple
      health problems, with effort and dedication and 24-hour care, many times these
      can be corrected.

PMID- 22640544
TI  - Overview of veterinary chiropractic and its use in pediatric exotic patients.
AB  - The scope of this article will be an introduction to veterinary chiropractic and
      its use in treating pediatric exotic patients. After discussing the general
      principles of human and veterinary chiropractic, the special considerations of
      adjusting exotic pediatric patients will be explored.

PMID- 22640545
TI  - Introduction to traditional Chinese veterinary medicine in pediatric exotic
      animal practice.
AB  - Exotic animals, both pediatric and adult, are amenable to TCVM diagnosis and
      respond well to the TCVM treatment including acupuncture and herbal medicine.
      With more documented clinical experience and experimental studies of the TCVM
      treatment of exotic animals, more diseases in more species will be identified to
      be effectively treated with the TCVM.

PMID- 22640546
TI  - Pediatrics of common and uncommon exotic animals.

PMID- 22640547
TI  - Comparison of five methods for genomic breeding value estimation for the common
      dataset of the 15th QTL-MAS Workshop.
AB  - BACKGROUND: Genomic breeding value estimation is the key step in genomic
      selection. Among many approaches, BLUP methods and Bayesian methods are most
      commonly used for estimating genomic breeding values. Here, we applied two BLUP
      methods, TABLUP and GBLUP, and three Bayesian methods, BayesA, BayesB and
      BayesCpi, to the common dataset provided by the 15th QTL-MAS Workshop to evaluate
      and compare their predictive performances. RESULTS: For the 1000 progenies
      without phenotypic values, the correlations between GEBVs by different methods
      ranged from 0.812 (GBLUP and BayesCpi) to 0.997 (TABLUP and BayesB). The
      accuracies of GEBVs (measured as correlations between true breeding values (TBVs)
      and GEBVs) were from 0.774 (GBLUP) to 0.938 (BayesCpi) and the biases of GEBVs
      (measure as regressions of TBVs on GEBVs) were from 1.033 (TABLUP) to 1.648
      (GBLUP). The three Bayesian methods and TABLUP had similar accuracy and bias.
      CONCLUSIONS: BayesA, BayesB, BayesCpi and TABLUP performed similarly and
      satisfactorily and remarkably outperformed GBLUP for genomic breeding value
      estimation in this dataset. TABLUP is a promising method for genomic breeding
      value estimation because of its easy computation of reliabilities of GEBVs and
      its easy extension to real life conditions such as multiple traits and
      consideration of individuals without genotypes.

PMID- 22640548
TI  - Time to diagnosis in young-onset dementia as compared with late-onset dementia.
AB  - BACKGROUND: The extent to which specific factors influence diagnostic delays in
      dementia is unclear. Therefore, the aim of the present study was to compare
      duration from symptom onset to diagnosis for young-onset dementia (YOD) and late
      onset dementia (LOD) and to assess the effect of age at onset, type of dementia,
      gender, living situation, education and family history of dementia on this
      duration. METHOD: Data on 235 YOD and 167 LOD patients collected from caregivers
      from two prospective cohort studies were used. Multiple linear regression
      analysis was performed. RESULTS: The duration between symptom onset and the
      diagnosis of YOD exceeded that of LOD by an average of 1.6 years (2.8 v. 4.4
      years). Young age and being diagnosed with frontotemporal dementia were related
      to increases in the time to diagnosis. Subjects with vascular dementia
      experienced shorter time to diagnosis. CONCLUSIONS: There is a need to raise
      special awareness of YOD to facilitate a timely diagnosis.

PMID- 22640550
TI  - Campylobacter spp., C. jejuni and C. upsaliensis infection-associated factors in
      healthy and ill dogs from clinics in Cordoba, Spain. Screening tests for
      antimicrobial susceptibility.
AB  - A microbiological and epidemiological survey examining Campylobacter species
      related infection in dogs from clinics in Cordoba (Southern Spain) was performed
      from May 2007 to March 2008. Three-hundred and six rectal swabs were taken from
      both ill and healthy dogs, and an epidemiological questionnaire was filled out.
      The isolated bacterial strains were identified by means of multiplex polymerase
      chain reaction (PCR). The prevalence factors for Campylobacter spp., C. jejuni
      and C. upsaliensis infection were determined by logistic regression. An
      antimicrobial susceptibility screening test was performed using the agar disk
      diffusion method. Campylobacter species were isolated from 102 samples. Forty
      strains (35.2%) were identified as Campylobacter jejuni, 60 strains (58.8%) as
      Campylobacter upsaliensis and two strains (2%) as Campylobacter spp. The sampling
      season was a prevalence factor for C. jejuni infection, while the age of the dog
      was a prevalence factor for Campylobacter spp. and C. upsaliensis infection.
      Enteric disease was a prevalence factor for Campylobacter spp., C. jejuni and C.
      upsaliensis infection. The antimicrobial susceptibility test indicated that
      gentamicin and erythromycin were the most effective antibiotics, with 97.8% and
      88% strains sensitive to the antibiotics, respectively.

PMID- 22640549
TI  - Are perceived stress, depressive symptoms and religiosity associated with alcohol
      consumption? A survey of freshmen university students across five European
      countries.
AB  - BACKGROUND: The aim of this study was to investigate the association of perceived
      stress, depressive symptoms and religiosity with frequent alcohol consumption and
      problem drinking among freshmen university students from five European countries.
      METHODS: 2529 university freshmen (mean age 20.37, 64.9% females) from Germany (n
      = 654), Poland (n = 561), Bulgaria (n = 688), the UK (n = 311) and Slovakia (n =
      315) completed a questionnaire containing the modified Beck Depression Inventory
      for measuring depressive symptoms, the Cohen's perceived stress scale for
      measuring perceived stress, the CAGE-questionnaire for measuring problem drinking
      and questions concerning frequency of alcohol use and the personal importance of
      religious faith. RESULTS: Neither perceived stress nor depressive symptoms were
      associated with a high frequency of drinking (several times per week), but were
      associated with problem drinking. Religiosity (personal importance of faith) was
      associated with a lower risk for both alcohol-related variables among females.
      There were also country differences in the relationship between perceived stress
      and problem drinking. CONCLUSION: The association between perceived stress and
      depressive symptoms on the one side and problem drinking on the other
      demonstrates the importance of intervention programs to improve the coping with
      stress.

PMID- 22640551
TI  - Molecular characterization and clonal genetic diversity of methicillin-resistant
      Staphylococcus aureus of pig origin in Taiwan.
AB  - Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is an
      emerging public health threat. The aims of this study were to identify nasal
      carriage of MRSA in finishing pigs from different geographical areas of Taiwan
      and to compare the genetic features of LA-MRSA with other countries. A total of
      299 swine nasal samples were collected from 11 counties in western Taiwan with
      220 identified MRSA isolates characterized by spa, SCCmec, MLST, pulsed-field gel
      electrophoresis (PFGE), antibiogram, and Panton-Valentine leukocidin (PVL) toxin
      genes. A widespread LA-MRSA clone, ST9-t899-PVL-negative, was detected as the
      predominant (91.6%) clone in Taiwan pigs, and a novel spa type t7616 was
      identified. Most isolates carried SCCmec type V but lacked ccrC gene (98.8%), a
      particular feature that was observed for the first time. The integration of
      minimum spanning trees (MST) based on a PFGE distance matrix and geographical
      information showed high genetic diversity among ST9-t899 isolates with three
      unique subpopulations identified in two counties that are nearby each other.
      Multidrug resistance (MDR) was prevalent in isolates from different counties with
      more than 80% resistance to erythromycin, ciprofloxacin, gentamicin,
      tetracycline, and clindamycin. In conclusion, this study reported the first
      identified LA-MRSA clone of MDR-ST9-t899-V lacking ccrC dominant in pig farms in
      western Taiwan that differed from ST398 in Europe and North America. Close
      monitoring of this MDR unique clone is warranted to survey its spread from
      livestock to humans.

PMID- 22640552
TI  - Quercetin impairs the reproductive potential of male mice.
AB  - Oxidative stress is a leading cause of male infertility. To combat this, germ
      cells and spermatozoa are endowed with various enzymes, vitamins and proteins.
      Certain other components of food, including bioflavonoids, also provide
      protection against free radicals. This study analysed the effect of quercetin, a
      bioflavonoid, on male reproductive function in adult mice, after intraperitoneal
      treatment with varying concentrations of quercetin (2, 8 and 20 mg kg(-1)  b.wt.)
      for 2 weeks. Quercetin increased the generation of reactive oxygen species and
      lipid peroxidation in the testis with concomitant decrease in sperm count and
      motility in a dose-dependent manner. Activities of antioxidant enzymes catalase,
      superoxide dismutase and levels of reduced glutathione were found to be decreased
      in a dose-dependent manner. Also, the levels of oxidised glutathione were
      increased leading to a shift in redox ratio. The testicular histomorphology was
      also altered dose dependently. Germ cell kinetic study revealed significant loss
      of various germ cell populations with increasing dose of quercetin.
      Interestingly, there was a reduction in germinal epithelium thickness concomitant
      with an increase in seminiferous tubule lumen diameter. In conclusion, the
      deleterious effects of quercetin on germ cells could be attributed to its pro
      oxidant ability that might affect the Sertoli cell functions.

PMID- 22640553
TI  - Critical Main-Chain Length for Conformational Conversion From 3(10)-Helix to
      alpha-Helix in Polypeptides.
AB  - Abstract   To assess the minimal peptide length required for the stabilization of
      the a-helix relative to the 3(10)-helix in Aib-rich peptides, we have solved the
      X-ray diffraction structures of the terminally blocked sequential hexa- and
      octapeptides with the general formula -(Aib-L-Ala)(n)-(n = 3 and 4,
      respectively). The hexapeptide molecules are completely 3(10)-helical with four 1
      <- 4 intramolecular N-H ... O=C H-bonds. On the other hand, the octapeptide
      molecules are essentially alpha-helical with four 1 <- 5 H-bonds; however, the
      helix is elongated at the N-terminus, with two 1 <- 4 H-bonds, giving these
      molecules a mixed alpha/3(10)-helical character. In both compounds the right
      handed screw sense of the helix is dictated by the presence of the Ala residues
      of L-configuration. This study represents the first experimental proof for a
      3(10) ->alpha-helix conversion in the crystal state induced by peptide backbone
      lengthening only.

PMID- 22640560
TI  - Exam-indicated cerclage in patients with fetal membranes at or beyond external
      os: a retrospective evaluation.
AB  - AIM: To evaluate pregnancy outcome in women with fetal membranes at or beyond
      external os who underwent exam-indicated cerclage or conservative management.
      MATERIAL AND METHODS: Retrospective cohort study including 52 patients with fetal
      membranes at or beyond external os between 17 and 27 weeks of gestation, treated
      in two third-level hospitals, between January 2001 and April 2009. The outcomes
      of interest of the study, prolongation of pregnancy and neonatal survival rate,
      were stratified according to type of management, parity, clinical conditions and
      blood tests at admission and calculated using the Kaplan-Meier algorithm.
      RESULTS: Of 52 women, 37 received exam-indicated cerclage and 15 were managed
      conservatively. The rate of patients still pregnant beyond 180 days within the
      cerclage group differed significantly from those of the conservative management
      group (80% vs 0%, respectively) (P-value<0.001). No difference has been found
      according to neonatal survival (82% versus 53%, respectively). CONCLUSION: Exam
      indicated cerclage appears to prolong gestation compared to expectant management.

PMID- 22640561
TI  - Dacryops of the lacrimal gland in a dog.
AB  - A case of congenital lacrimal cyst or dacryops of the lacrimal gland in an 8
      month-old Neapolitan Mastiff dog is reported. The dog presented with a swelling
      dorsolateral to the left globe, which had been present since birth. In addition,
      hyperplasia and prolapse of the superficial gland of the left nictitating
      membrane, and bilateral macropalpebral fissure and 'diamond eye' conformation
      were apparent. On manual eversion of the upper eyelid, a subconjunctival mass was
      visible that was translucent and pink and affected the upper conjunctival fornix.
      B-mode ultrasonography revealed the presence of an echolucent thin-walled cystic
      structure measuring 15 by 12 mm and containing an echodense border and a
      distended tubular fluid-filled structure that extended posteriorly. A viscous and
      transparent fluid was aspirated from the lesion. Surgery was performed to excise
      the lesion, reposition the nictitans gland, and correct the morphology of the
      palpebral fissure. Histopathology confirmed the mass to be a cyst and distended
      duct of the lacrimal gland. Although tear secretion was compromised, resection of
      the cyst was curative.

PMID- 22640559
TI  - Nef functions in BLT mice to enhance HIV-1 replication and deplete CD4+CD8+
      thymocytes.
AB  - BACKGROUND: The outcome of untreated HIV-1 infection is progression to AIDS and
      death in nearly all cases. Some important exceptions are the small number of
      patients infected with HIV-1 deleted for the accessory gene, nef. With these
      infections, disease progression is entirely suppressed or greatly delayed.
      Whether Nef is critical for high levels of replication or is directly cytotoxic
      remains controversial. The major problem in determining the role of Nef in
      HIV/AIDS has been the lack of tractable in vivo models where Nef's complex
      pathogenic phenotype can be recapitulated. RESULTS: Intravenous inoculation (3000
      to 600,000 TCIU) of BLT humanized mice with HIV-1LAI reproducibly establishes a
      systemic infection. HIV-1LAI (LAI) replicates to high levels (peak viral load in
      blood 8,200,000 +/- 1,800,000 copies of viral RNA/ml, range 3,600,000 to
      20,400,000; n = 9) and exhaustively depletes CD4+ T cells in blood and tissues.
      CD4+CD8+ thymocytes were also efficiently depleted but CD4+CD8- thymocytes were
      partially resistant to cell killing by LAI. Infection with a nef-deleted LAI
      (LAINefdd) gave lower peak viral loads (1,220,000 +/- 330,000, range 27,000 to
      4,240,000; n = 17). For fourteen of seventeen LAINefdd-infected mice, there was
      little to no loss of either CD4+ T cells or thymocytes. Both LAI- and LAINefdd
      infected mice had about 8% of total peripheral blood CD8+ T cells that were
      CD38+HLA-DR+ compared <1% for uninfected mice. Three exceptional LAINefdd
      infected mice that lost CD4+ T cells received 600,000 TCIU. All three exhibited
      peak viral loads over 3,000,000 copies of LAINefdd RNA/ml. Over an extended time
      course, substantial systemic CD4+ T cell loss was observed for the three mice,
      but there was no loss of CD4+CD8+ or CD4+CD8- thymocytes. CONCLUSION: We conclude
      Nef is necessary for elevated viral replication and as a result indirectly
      contributes to CD4+ T cell killing. Further, Nef was not necessary for the
      activation of peripheral blood CD8+ T cells following infection. However,
      CD4+CD8+ thymocyte killing was dependent on Nef even in cases of elevated
      LAINefdd replication and T cell loss. This depletion of thymic T cell precursors
      may be a significant factor in the elevated pathogenicity of CXCR4 trophic HIV-1.

PMID- 22640562
TI  - The pepper RNA-binding protein CaRBP1 functions in hypersensitive cell death and
      defense signaling in the cytoplasm.
AB  - The regulation of gene expression via post-transcriptional modification by RNA
      binding proteins is crucial for plant disease and innate immunity. Here, we
      report the identification of the pepper (Capsicum annuum) RNA-binding protein1
      gene (CaRBP1) as essential for hypersensitive cell death and defense signaling in
      the cytoplasm. CaRBP1 contains an RNA recognition motif and is rapidly and
      strongly induced in pepper by avirulent Xanthomonas campestris pv. vesicatoria
      (Xcv) infection. CaRBP1 displays in vitro RNA- and DNA-binding activity and in
      planta nucleocytoplasmic localization. Transient expression of CaRBP1 in pepper
      leaves triggers cell-death and defense responses. Notably, cytoplasmic
      localization of CaRBP1, mediated by the N-terminal region of CaRBP1, is essential
      for the hypersensitive cell-death response. Silencing of CaRBP1 in pepper plants
      significantly enhances susceptibility to avirulent Xcv infection. This is
      accompanied by compromised hypersensitive cell death, production of reactive
      oxygen species in oxidative bursts, expression of defense marker genes and
      accumulation of endogenous salicylic acid and jasmonic acid. Over-expression of
      CaRBP1 in Arabidopsis confers reduced susceptibility to infection by the
      biotrophic oomycete Hyaloperonospora arabidopsidis. Together, these results
      suggest that cytoplasmic localization of CaRBP1 is required for plant signaling
      of hypersensitive cell-death and defense responses.

PMID- 22640563
TI  - Endocrine effects of inhaled budesonide compared with inhaled fluticasone
      propionate and oral prednisolone in healthy Beagle dogs.
AB  - Orally administered corticosteroids are commonly used to treat chronic
      respiratory disease, but adverse effects suggest that the inhalation route may be
      safer. To compare the systemic effects of inhaled and oral corticosteroids, a
      prospective, randomised, placebo-controlled cross-over study was conducted. Six
      healthy neutered female Beagle dogs were randomly allocated to four treatment
      groups: (1) budesonide inhalation (200 MUg twice daily); (2) fluticasone
      inhalation (250 MUg twice daily); (3) oral prednisolone (1mg/kg once daily); and
      (4) placebo inhalation (room air twice daily). Each treatment and wash-out period
      lasted 4 weeks. The endocrine status of each dog was assessed on days 0, 28 and
      35 using the adrenocorticotropic hormone (ACTH) stimulation test. The effects of
      treatments were assessed using a linear mixed effects model. After the 4 week
      treatment period, a significant decrease was observed in the basal serum cortisol
      level of the prednisolone group (P<0.03), and a decrease was also seen in the
      ACTH-stimulated peak cortisol levels of both the prednisolone and fluticasone
      groups (P<0.001), compared with the budesonide group in which no suppression was
      detected. The results showed that cortisol production in dogs was strongly
      suppressed by oral prednisolone and by inhaled fluticasone.

PMID- 22640564
TI  - [True precocious puberty: a rare sequel after severe head trauma].

PMID- 22640565
TI  - [Bronchial carcinoid as a cause of treatment refractory asthma].

PMID- 22640566
TI  - [Continuous partial epilepsy and hemiparesis].

PMID- 22640567
TI  - Should risky treatments be reserved for secondary prevention? Theoretical
      considerations regarding risk-benefit tradeoffs.
AB  - OBJECTIVE: Clinical intuition suggests that risk-reducing treatments are more
      beneficial for patients with greater risk of disease. This intuition contributes
      to our rationale for tolerating greater adverse event risk in the setting of
      secondary prevention of certain diseases such as myocardial infarction or stroke.
      However, under certain conditions treatment benefits may be greater in primary
      prevention, even when the treatment carries harmful adverse effect potential.
      STUDY DESIGN AND SETTING: We present simple decision-theoretic models that
      illustrate conditions of risk and benefit under which a treatment is predicted to
      be more beneficial in primary than in secondary prevention. RESULTS: The models
      cover a spectrum of possible clinical circumstances, and demonstrate that net
      benefit in primary prevention can occur despite no benefit (or even net harm) in
      secondary prevention. CONCLUSION: This framework provides a rationale for
      extending the familiar concept of balancing risks and benefits to account for
      disease-specific considerations of primary vs. secondary prevention.

PMID- 22640568
TI  - Diagnostic accuracy of clinical symptoms in obstructive airway diseases varied
      within different health care sectors.
AB  - OBJECTIVE: To determine the diagnostic accuracy and diagnostic patterns of
      clinical symptoms in patients suspected to suffer from obstructive airway
      diseases (OADs) within different health care sectors. STUDY DESIGN AND SETTING:
      Ten general practices (219 patients), one practice of pneumologists (259
      patients) and one specialist hospital (300 patients). Sensitivities,
      specificities, positive (LR+), and negative (LR-) likelihood ratios of clinical
      symptoms were compared with lung function testing. RESULTS: Thirty-one percent
      had chronic obstructive pulmonary disease (COPD), 21% had asthma. Sensitivities
      increased and specificities decreased from outpatient to hospital setting. The
      multivariate model of adjusted likelihood ratios for COPD showed LR+=4.86 (95%
      confidence interval [CI]=2.09-11.29) and LR-=0.07 (95% CI=0.01-0.43) of the
      combination "wheezing," "dyspnea when going upstairs," "smoking" in general
      practice. In hospital, the combination "dyspnea when going upstairs," "dyspnea
      during minimal exercise," and "smoking" showed LR+=3.34 (95% CI=2.08-5.31) and LR
      =0.02 (95% CI=0.01-0.12). The combination "no coughing," "dyspnea attacks," and
      "no smoking" showed LR+=4.08 (95% CI=1.67-10.4) and LR-=0.24 (95% CI=0.12-0.58)
      for asthma in general practice. The combination "dyspnea attacks" and "no dyspnea
      when walking" showed LR+=6.48 (95% CI=1.01-40.94) and LR-=0.28 (95% CI=0.11-0.75)
      for asthma in hospital. CONCLUSION: Clinical decision rules for OAD need to be
      derived from original studies in their respective settings or assessed on their
      transferability to other settings.

PMID- 22640569
TI  - Semantically equivalent PubMed and Ovid-MEDLINE queries: different retrieval
      results because of database subset inclusion.

PMID- 22640570
TI  - Porcine MHC classical class I genes are coordinately expressed in superantigen
      activated mononuclear cells.
AB  - The expression of the major histocompatibility complex (MHC) classical class I
      genes is important for the adaptive immune response to target virus-infected
      cells and cancer cells. The up-regulation of the MHC is achieved by
      hormonal/cytokine signals including IFN-gamma-inducible elements. The swine
      leukocyte antigen (SLA), the MHC class I region of pigs, consists of the
      duplicated classical class I genes, SLA-1, SLA-2 and SLA-3, but the molecular
      mechanisms involved in their up-regulation after T cell stimulation have not been
      fully elucidated. In order to better understand some of the putative regulatory
      mechanisms of SLA class I gene expression in activated T cells, we examined the
      coordinated expression of the SLA classical class I, IFN-gamma and interferon
      regulatory factor-1 (IRF-1) genes in the peripheral blood mononuclear cells
      (PBMCs) of SLA homozygous Clawn miniature swine stimulated for 72 h with either
      IFN-gamma or an enterotoxin produced by Staphylococcus aureus. This enterotoxin,
      toxic shock syndrome-1 (TSST-1), is known to act as a superantigen (sAG) to
      activate the T cells in various vertebrate species. We showed by using mAbs and
      flow cytometry that the CD4(+)CD25(+) cell number of swine PBMCs was also
      increased by TSST-1 and to a lesser degree by IFN-gamma. Time course analyses of
      the expression of the IFN-gamma, IRF-1 and the three classical class I genes, SLA
      1, SLA-2, and SLA-3, in PBMCs by quantitative real-time PCR revealed a transitory
      response to TSST-1 or IFN-gamma stimulation. The IFN-gamma mRNA levels in the
      PBMCs were continuously up-regulated over the first 48 h by TSST-1 or IFN-gamma.
      In contrast, SLA class I expression moderately increased at 24h and then
      decreased to a baseline level or less at 72 h of IFN-gamma or TSST-1 stimulation.
      The three classical SLA class I genes showed similar expression kinetics,
      although SLA-3 mRNA level was consistently lower than those of SLA-1 and -2. The
      expression of IRF-1, a modulator of SLA expression, showed similar kinetics to
      those of the three classical SLA class I genes. The expression profiles detected
      by flow cytometry of the SLA molecules on the cell surface of PBMCs were
      maintained at a consistently high level during cell stimulation with either TSST
      1 or IFN-gamma, which was distinct from the kinetics of mRNA expression. These
      results showed that miniature swine SLA class I mRNA expression was effectively
      and equally up-regulated among the three loci and coordinately with IRF-1 gene
      expression after stimulation of T cell activation by sAG or IFN-gamma.

PMID- 22640571
TI  - Syntheses and antibacterial activity of Schiff bases from 16-isopropyl-5, 9
      dimethyltetracyclo [10.2.2.0(1, 10).0(4, 9)] hexadec-15-ene-5, 14-dicarboxylic
      acid.
AB  - 16-isopropyl-5, 9-dimethyltetracyclo [10.2.2.0(1, 10).0(4, 9)] hexadec-15-ene-5,
      14-dicarboxylic acid (1b) was prepared from rosin through a Diels-Alder addition
      reaction. Then, a group of Schiff bases derived from 1b was synthesised. Their
      structures were characterised by IR,(1)H-NMR, MS and elemental analysis. The
      antibacterial activities of these newly synthesised Schiff bases were also
      investigated. The results show that these compounds possess antibacterial
      activities against Staphylococcus aureus and Escherichia coli. Among them,
      compounds 5a, 5b and 5c, exhibit remarkable antibacterial activity against E.
      coli.

PMID- 22640572
TI  - Biomarkers in transplantation medicine: guide to the next level in
      immunosuppressive therapy.

PMID- 22640573
TI  - Effects of balance-focused interactive games compared to therapeutic balance
      classes for older women.
AB  - OBJECTIVE: The prospective pre-post control study was designed to evaluate the
      effect of introducing balance-focused interactive virtual-reality games to
      community-dwelling older women to improve their agility, balance and functional
      mobility. METHOD: The study was set in a senior citizens' club in Cheras, Kuala
      Lumpur, Malaysia. The participants were 36 community-dwelling older women.
      Participants were randomly divided into either a group undertaking balance
      focused virtual-reality games or a group doing therapeutic balance exercises. The
      program lasted 6 weeks and was conducted twice a week for 40 min during each
      session. As the main outcome measures, the results of the Ten Step Test (TST),
      postural sway (overall performance index, OPI) and the Timed Up and Go test (TUG)
      were measured pre- and post-intervention to evaluate agility, balance and
      functional mobility, respectively. RESULTS: Although both groups improved in OPI
      (F = 4.63, p < 0.001), TST (F = 46.15, p < 0.001) and TUG (F = 52.57, p = 0.03),
      combined time and group interaction only improved in the TUG (F = 4.54, p <
      0.05). No significant differences between the two groups were found in terms of
      TST (F = 0.02, p = 0.86), OPI (F = 0.66, p = 0.42), and TUG (F = 0.11, p = 0.74).
      CONCLUSION: Older people could improve their agility, balance and functional
      mobility by complementing therapeutic balance exercises with active participation
      in interactive virtual-reality games at home or in the community.

PMID- 22640574
TI  - Soft braces in the treatment of Adolescent Idiopathic Scoliosis (AIS) - Review of
      the literature and description of a new approach.
AB  - BACKGROUND: The use of soft braces to treat scoliosis has been described by
      Fischer as early as 1876. With the help of elastic straps, as the authors
      suggested, a corrective movement for individual curve patterns should be
      maintained in order to inhibit curve progression. Today this concept has been
      revived besides soft 3 point pressure systems. Some shortcomings have been
      revealed in literature in comparison with hard braces, however the concept of
      improving quality of life of a patient while under brace treatment should
      furtherly be considered as valuable. Purpose of this review is to gather the body
      of evidence existent for the use of soft braces and to present recent
      developments. METHOD: A review of literature as available on Pub Med was
      performed using the key words 'scoliosis' and 'soft brace' at first. The search
      was expanded using 'scoliosis' and the known trademarks (1) 'scoliosis' and
      'SpineCor', (2) 'scoliosis' and 'TriaC', (3) 'scoliosis' and 'St. Etienne brace',
      (4) 'scoliosis' and 'Olympe'. The papers considered for inclusion were new
      technical descriptions, preliminary results, cohort studies and controlled
      studies. RESULTS: When searching for the terms 'scoliosis' and 'SpineCor': 20
      papers have been found, most of them investigating a soft brace, for 'scoliosis'
      and 'TriaC': 7 papers displayed, for 'scoliosis' and 'St. Etienne brace': one
      paper displayed but not meeting the topic and for 'scoliosis' and 'Olympe': No
      paper displayed. Four papers found on the SpineCorTM were of prospective
      controlled or prospective randomized design. These papers partly presented
      contradictory results. Two papers were on soft Boston braces used in patients
      with neuromuscular scoliosis. DISCUSSION: There is a small but consistent body of
      evidence for the use of soft braces in the treatment of scoliosis. Contradictory
      results have been published for samples treated during the pubertal growth spurt.
      In a biomechanical analysis the reason for the lack of effectiveness during this
      period has been elaborated. Improved materials and the implementation of
      corrective movements respecting also the sagittal correction of the scoliotic
      spine will hopefully contribute to an improvement of the results achievable.
      CONCLUSIONS: The treatment of scoliosis using soft braces is supported by some
      papers providing a small body of evidence. During the growth spurt the use of
      soft braces is discussed contradictory. There is insufficient evidence to draw
      definite conclusions about effectiveness and safety of the intervention.

PMID- 22640575
TI  - Equine ambulatory practice: challenges and opportunities.
AB  - Current economic conditions make the practice of equine medicine challenging, to
      say the least. The downward trend in the US economy has had a huge impact on
      horse owners and equine veterinarians alike. Horses are expensive to keep; as
      such, economics are the driving factor in the problem of the unwanted horse.
      Under these conditions, efficient equine ambulatory practices are well-suited to
      weather the economic storm. As contributors to this issue of Veterinary Clinics
      of North America note, one can practice high-quality medicine and surgery without
      the overhead and expense of a large clinic. Ambulatory practitioners certainly
      face formidable challenges, but they also have opportunities to establish and
      secure a good future.

PMID- 22640576
TI  - Ambulatory equine practice management.
AB  - The horse owner not only expects outstanding care for their horse; they also
      recognize and appreciate a well-run equine practice. They expect their
      veterinarian to show up on time for appointments; they expect to receive
      decipherable invoices and statements on a regular basis and they appreciate an
      assistant who enhances the services that their veterinarian provides. A well
      managed ambulatory equine practice supports the ideals of both high standards of
      care and mobility. In fact, a poorly managed practice will ultimately impact the
      care that an equine veterinarian attempts to provide the horses in his or her
      care. Without careful attention to profitability and efficiency, the practice's
      ability to grow and develop with emerging therapies and technologies is
      impossible. Furthermore, a poorly managed practice will significantly contribute
      to the frustration that an equine veterinarian feels after working long hours and
      receiving only nominal pay.

PMID- 22640577
TI  - Technology and the ambulatory equine practitioner: implementing and affording the
      21st century.
AB  - Purchasing new or used capital assets involves both emotional and financial
      components in the decision making process. In addition, there are intangible
      factors such as client perceptions and expectations that fit into the equation.
      Identify the facts from a business perspective and then define whether this
      investment (expense) is good for the practice and fits with the short- and long
      term growth strategies. Ask the tough questions, analyze the numbers, understand
      the clients' needs, and tie this together with the practice brand and strategic
      objectives. The informed and prepared buyer is usually successful in making the
      right decision.

PMID- 22640578
TI  - Do you know your equine practice clients?
AB  - A healthy group of loyal clients is of the utmost importance for a healthy
      practice.Knowing the clients' expectations and making every effort to exceed them
      when clients meet with the veterinarian or visit the clinic will result in
      continued client satisfaction. Clients will show loyalty to a veterinarian when
      they perceive that the care provided to them suits them and their animal and
      exceeds their expectations.

PMID- 22640579
TI  - Ambulatory medicine in equine practice.
AB  - The scope of medical problems encountered by the equine ambulatory practitioner
      is immense; there is a wealth of information available to ambulatory
      practitioners pertaining to specific medical topics. It is certainly possible to
      practice high-quality equine medicine in a field setting. However, hospital
      referral should be offered to clients for conditions not conducive to successful
      treatment in the field. Prompt referral of difficult cases is a sign that the
      practitioner wants the best treatment for the patient and is often gladly
      accepted by the client. When surgical or hospital referral is not an option, it
      is imperative that the ambulatory practitioner not only offer humane alternatives
      but also inform and educate horse owners on equine suffering and welfare issues
      so that clients do not have unreasonable expectations of a positive outcome.

PMID- 22640580
TI  - The ambulatory practitioner and the referral center: two perspectives in equine
      surgery.
AB  - Practicing at a referral center makes one aware of the necessity for consistent
      clear communication with the referring veterinarians. The referring veterinarian
      is ultimately the primary client of the referral center and should be respected
      as such. Once the necessary care has been provided, the client and horse should
      be returned to the care of the referring veterinarian. It is important that the
      referring veterinarian stay involved in the case and communicate if they wish for
      more or less contact with the referral center.

PMID- 22640581
TI  - Wound care in horses.
AB  - Care of equine wounds in the field can be a challenging endeavor. Many times,
      wound care is complicated by chronicity or by prior inappropriate care in
      addition to the great degree of tissue trauma that occurred when the horse was
      wounded. Recognizing involvement of synovial structures, loss of skin, and damage
      to bone are critical in the initial examination of wounds and will guide future
      care. Education of clients is also important in that preparing them for possible
      outcomes during healing may help improve compliance and proper treatment of
      wound. Owners and trainers often perform much of the daily care and monitoring of
      equine wounds and thus can greatly assist or impede the progress. Bandaging is
      important to management of equine wounds-especially on the limbs-and is sometimes
      overlooked because of its labor-intensive nature and the desire for a spray,
      ointment, or salve that will heal the wound. The practitioner that improves and
      utilizes his or her understanding of the wound-healing process in concert with
      his or her knowledge of local anatomy will be the one who is best equipped to
      care for wounds in ambulatory practice.

PMID- 22640582
TI  - Lameness and performance evaluation in ambulatory practice.
AB  - Lameness and performance evaluation can be one of the most rewarding aspects of
      equine veterinary practice. There is a misconception that it depends on new
      sophisticated and expensive diagnostic modalities, when the reality is that
      knowing where and when to use these modalities form the real art of equine
      lameness practice. The most expensive ultrasound machine in the world is not very
      diagnostic if applied to the wrong limb. The art of lameness practice is vested
      in knowledge of horsemanship, an understanding of anatomy and function, and
      inquiring senses to sort out what the horse and his handlers are telling you. The
      ability to listen to both and figure out a horse's lameness problem will be one
      of the most valuable services experiences the equine ambulatory clinician can
      provide for his or her clientele.

PMID- 22640583
TI  - The equine practitioner-farrier relationship: building a partnership.
AB  - The importance of hoof care in maintaining the health and soundness of a horse
      cannot be overstated. The aphorism, "No foot, no horse" still holds true. For
      equine ambulatory practitioners, the time devoted to a thorough understanding of
      the equine digit and it's care is well worth the investment. The effort devoted
      to developing good relationships with individuals who will likely be responsible
      for implementing the changes suggested as a result of that understanding will be
      rewarded many times over in the course of the equine ambulatory practitioner's
      career.

PMID- 22640584
TI  - The approach to the equine dermatology case in practice.
AB  - A logical and thorough clinical investigation should provide the best basis for
      the diagnosis of skin diseases. Where no diagnosis can be reached despite a full
      range of investigations, the clinician can justifiably attempt symptomatic
      treatment, but it is always better to focus treatment on a specific condition
      based on properly accumulated and tested clinical evidence. Unfortunately, in
      equine dermatology there are few text descriptions of the majority of the
      conditions encountered in practice. While a few diseases are well recognized,
      there is still little consensus on the best treatments for many of them.
      Individual veterinarians will have treatments that they rely on, but frequently
      the same treatment applied by another person inexplicably fails to work in the
      same way. In dermatology cases, there is no substitute for experience.
      Referencing to quality textbooks and to colleagues who might have encountered the
      condition before is often advisable. Unusual presentations are frequently
      encountered in horses. For example, there are many manifestations of the
      pemphigus group of diseases, and not all will have a clear diagnostic pathway. It
      is important to remember that the skin is one of the biggest organs in the body
      and yet little is known of its function and pathology! While there are many
      significant primary dermatologic conditions, there are also important systemic
      diseases that have more or less pathognomonic secondary dermatologic signs; this
      makes the proper clinical examination even more imperative. One of the biggest
      problems with equine dermatology is the dearth of scientific reports. Many
      experienced clinicians have much useful information, but this may never reach the
      rest of the profession. Also there are few useful reference textbooks dedicated
      to the equine species. Equine dermatology most likely suffers the most of all
      disciplines in this respect. As a result, every clinician is expected to reinvent
      the wheel! There is a need for publications and discussions about the problem
      cases; even the commonest skin diseases are poorly understood. To make the most
      use of the supporting specialties of microbiology and pathology, it is important
      to involve the relevant specialists in the diagnostic process. This means that
      these specialists must have as much information as they can get; it helps
      enormously if a photograph can be taken of the disease. Without such information,
      pathologists and microbiologists may make gratuitous statements about treatment
      options. For example, a biopsy from an upper eyelid lesion might be easily
      diagnosed as a sarcoid, and any statement concerning wide surgical excision might
      be both misleading and nonsensical but would be totally avoidable had the
      specialist been provided more information. The approach to the dermatologic case
      requires a logical and exhaustive clinical investigation involving a thorough
      history and a detailed clinical examination. Diagnostic tests should be carefully
      selected to rule-out or confirm a suspected diagnosis. Frequent reexaminations
      are often required because it is sometimes difficult to establish the primary
      condition: this is often due to extensive self-inflicted trauma or iatrogenic
      interference by the owner. By proceeding in a systematic and stepwise manner,
      equine ambulatory clinicians can frequently bring dermatologic problems to a
      successful resolution.

PMID- 22640585
TI  - Ophthalmology in equine ambulatory practice.
AB  - Equine practitioners examine patient eyes on a daily basis. Indications range
      from inspection of normal anatomy to treatment of traumatized eyes to workups of
      sight threatening inflammatory or neoplastic ocular conditions. Assessment of
      equine eyes requires practitioners to take time to create a good "exam room" in
      the field and administer appropriate restraint, sedation and/or regional
      anesthesia to facilitate thorough examination. Accurate diagnosis and treatment
      of equine eye problems requires skill in ocular surface staining and cytology,
      and basic proficiency in standing surgery. Expertise in digital photography
      optimizes client education and case management. As some equine eye problems
      benefit from intense medical treatment or advanced surgical care, practitioners
      should be familiar with the options offered at specialty centers, and recognize
      cases that would benefit from referral. Finally, blindness is not uncommon in
      horses. Practitioners can counsel clients that own blind horses on the best
      options for managing sight loss.

PMID- 22640586
TI  - Reproduction in ambulatory practice.
AB  - The value of providing equine reproductive services in ambulatory setting is well
      established. Ambulatory practice has been, and will most likely continue to be,
      the primary provider of equine reproductive veterinary services. The limitations
      for performing various reproductive procedures in an ambulatory setting are those
      imposed by the amount of equipment and supplies that must be brought to the
      patient, as well as those imposed when procedures require additional assistance.
      This is analogous to human medical care: the ambulance cannot substitute for a
      hospital but it can certainly provide significant assistance. Similarly, although
      excellent reproductive service can be provided in ambulatory practice, a fair
      number of advanced techniques and procedures requiring laboratory conditions,
      equipment, and personnel are difficult to provide from the back of a vehicle.

PMID- 22640587
TI  - Equine wellness care in ambulatory practice.
AB  - Clients want dependable veterinary care and to understand how the services will
      benefit and meet their horse's needs. Wellness visits provide ambulatory
      practitioners with great opportunities to strengthen the doctor-client-patient
      bond; effective communication with clients during wellness visits, where new
      literature or facts can be presented, can offer opportunities for demonstrating
      the value of having the veterinarian maintain a primary role in disease control.
      The criteria for selecting vaccines, interpreting FECs, and diagnosing dental
      pathology require the continued need for veterinary involvement. When providing
      wellness services, veterinarians should discuss those services, the reasons for
      them, as well as the possibility of adverse reactions. In so doing, the
      veterinarian is able to clearly distinguish himself or herself from a technician
      who is merely giving a "shot." Although some of these services can be performed
      by clients and lay professionals, the knowledge and training that veterinarians
      bring to these tasks add benefits to the horse beyond the services provided. For
      example, by targeting treatment and conveying the goals and limitations of FECs
      and deworming to clients, the speed at which anthelmintic resistance occurs will
      be diminished, and veterinarians will regain control over equine parasite
      management. Additional client education, such as demonstrating dental pathology
      to clients and how veterinary treatment benefits their horse, will not only
      improve the health of the horse further but also solidify the veterinarian's role
      in preventative medicine. While all components of a wellness program were not
      detailed here, services such as nutritional consultation, blood work, and
      lameness evaluation should be offered based on the practice's equine population.
      With the increasing population of geriatric horses, dentistry, nutrition, blood
      work, and lameness should be assessed annually or biannually. Each practice has
      its own set of criteria that could be included under the umbrella of
      "preventative medicine." It is during these times, when the client is most
      relaxed and not concerned about a serious health problem, that it is easiest to
      demonstrate the significance of veterinarians in equine wellness care.

PMID- 22640588
TI  - Prepurchase examination in ambulatory equine practice.
AB  - Prepurchase examination provides a significant opportunity for veterinarians to
      offer an important professional service to the equine industry. When the service
      is performed competently and ethically, prospective buyers and sellers will
      recommend the examining veterinarian to fellow horse owners and professionals. To
      become comfortable with and skilled at performing prepurchase examinations, a
      veterinarian must understand the operational challenges associated with this
      service-and master them. Veterinarians performing prepurchase examinations should
      address the needs and manage the expectations of the prospective buyer, treat the
      seller and all parties with professional courtesy, be familiar with the intended
      use of the horse, competently perform a thorough physical examination, and pay
      close attention to the medical record and report. Communicate clearly with all
      parties before, during, and after the examination. Feedback from staff and
      colleagues is critical to improving and refining the services offered. The
      veterinarian should work with staff to evaluate the processes used to deliver the
      prepurchase examination experience to clients and consult with mentors who are
      skilled in performing these services. Sharing your ideas for improving
      prepurchase examination with equine colleagues is a service to the veterinary
      profession and to the horse. Performing a prepurchase examination in the way
      described may sound like a "tall order," but once patient care and service goals
      have been established, staff has been trained, and the process has been defined
      the challenges become opportunities. The rewards include satisfied clients,
      reduced liability risk, increased profitability, and the satisfaction of having
      performed an interesting, valuable task to the best of one's abilities.

PMID- 22640589
TI  - Ambulatory practice.

PMID- 22640591
TI  - Comparison of the analyses of the XVth QTLMAS common dataset II: QTL analysis.
AB  - BACKGROUND: The QTLMAS XVth dataset consisted of the pedigrees, marker genotypes
      and quantitative trait performances of 2,000 phenotyped animals with a half-sib
      family structure. The trait was regulated by 8 QTL which display additive,
      imprinting or epistatic effects. This paper aims at comparing the QTL mapping
      results obtained by six participants of the workshop. METHODS: Different
      regression, GBLUP, LASSO and Bayesian methods were applied for QTL detection. The
      results of these methods are compared based on the number of correctly mapped
      QTL, the number of false positives, the accuracy of the QTL location and the
      estimation of the QTL effect. RESULTS: All the simulated QTL, except the
      interacting QTL on Chr5, were identified by the participants. Depending on the
      method, 3 to 7 out of the 8 QTL were identified. The distance to the real
      location and the accuracy of the QTL effect varied to a large extent depending on
      the methods and complexity of the simulated QTL. CONCLUSIONS: While all methods
      were fairly efficient in detecting QTL with additive effects, it was clear that
      for non-additive situations, such as parent-of-origin effects or interactions,
      the BayesC method gave the best results by detecting 7 out of the 8 simulated
      QTL, with only two false positives and a good precision (less than 1 cM away on
      average). Indeed, if LASSO could detect QTL even in complex situations, it was
      associated with too many false positive results to allow for efficient GWAS.
      GENMIX, a method based on the phylogenies of local haplotypes, also appeared as a
      promising approach, which however showed a few more false positives when compared
      with the BayesC method.

PMID- 22640590
TI  - Turning sex inside-out: Peripheral contributions to sexual differentiation of the
      central nervous system.
AB  - Sexual differentiation of the nervous system occurs via the interplay of
      genetics, endocrinology and social experience through development. Much of the
      research into mechanisms of sexual differentiation has been driven by an implicit
      theoretical framework in which these causal factors act primarily and directly on
      sexually dimorphic neural populations within the central nervous system. This
      review will examine an alternative explanation by describing what is known about
      the role of peripheral structures and mechanisms (both neural and non-neural) in
      producing sex differences in the central nervous system. The focus of the review
      will be on experimental evidence obtained from studies of androgenic
      masculinization of the spinal nucleus of the bulbocavernosus, but other systems
      will also be considered.

PMID- 22640592
TI  - Estimated cumulative incidence of West Nile virus infection in US adults, 1999
      2010.
AB  - West Nile virus (WNV) was first recognized in the USA in 1999. We estimated the
      cumulative incidence of WNV infection in the USA from 1999 to 2010 using recently
      derived age- and sex-stratified ratios of infections to WNV neuroinvasive disease
      (WNND) and the number of WNND cases reported to national surveillance. We
      estimate that over 3 million persons have been infected with WNV in the USA, with
      the highest incidence rates in the central plains states. These 3 million
      infections would have resulted in about 780 000 illnesses. A substantial number
      of WNV infections and illnesses have occurred during the virus' first decade in
      the USA.

PMID- 22640594
TI  - Identification of a metabolic bottleneck for cold acclimation in Arabidopsis
      thaliana.
AB  - Central carbohydrate metabolism of Arabidopsis thaliana is known to play a
      crucial role during cold acclimation and the acquisition of freezing tolerance.
      During cold exposure, many carbohydrates accumulate and a new metabolic
      homeostasis evolves. In the present study, we analyse the diurnal dynamics of
      carbohydrate homeostasis before and after cold exposure in three natural
      accessions showing distinct cold acclimation capacity. Diurnal dynamics of
      soluble carbohydrates were found to be significantly different in cold-sensitive
      and cold-tolerant accessions. Although experimentally determined maximum turnover
      rates for sucrose phosphate synthase in cold-acclimated leaves were higher for
      cold-tolerant accessions, model simulations of diurnal carbohydrate dynamics
      revealed similar fluxes. This implied a significantly higher capacity for sucrose
      synthesis in cold-tolerant than cold-sensitive accessions. Based on this
      implication resulting from mathematical model simulation, a critical temperature
      for sucrose synthesis was calculated using the Arrhenius equation and
      experimentally validated in the cold-sensitive accession C24. At the critical
      temperature suggested by model simulation, an imbalance in photosynthetic carbon
      fixation ultimately resulting in oxidative stress was observed. It is therefore
      concluded that metabolic capacities at least in part determine the ability of
      accessions of Arabidopsis thaliana to cope with changes in environmental
      conditions.

PMID- 22640595
TI  - [The role of marketing in health services].

PMID- 22640596
TI  - Two new alkaloid galactosides from the kernel of Prinsepia uniflora.
AB  - Two new alkaloid galactosides have been isolated from the kernel of Prinsepia
      uniflora. Their structures were elucidated as 5-[(alpha-D-galactopyranosyloxy)
      methyl]-1H-pyrrole-2-carbaldehyde (1) and 6-[(alpha-D-galactopyranosyloxy)
      methyl]-3-pyridinol (2) by various spectroscopic means including HR-ESI-MS, IR,
      1D and 2D NMR. The determined structures were characterized with a unit of
      galactose which is rarely seen in the previously isolated pyrrole and pyridinol
      compounds.

PMID- 22640593
TI  - The trinity of the cortical actin in the initiation of HIV-1 infection.
AB  - For an infecting viral pathogen, the actin cortex inside the host cell is the
      first line of intracellular components that it encounters. Viruses devise various
      strategies to actively engage or circumvent the actin structure. In this regard,
      the human immunodeficiency virus-1 (HIV-1) exemplifies command of cellular
      processes to take control of actin dynamics for the initiation of infection. It
      has becomes increasingly evident that cortical actin presents itself both as a
      barrier to viral intracellular migration and as a necessary cofactor that the
      virus must actively engage, particularly, in the infection of resting CD4 blood T
      cells, the primary targets of HIV-1. The coercion of this most fundamental
      cellular component permits infection by facilitating entry, reverse
      transcription, and nuclear migration, three essential processes for the
      establishment of viral infection and latency in blood T cells. It is the purpose
      of this review to examine, in detail, the manifestation of viral dependence on
      the actin cytoskeleton, and present a model of how HIV utilizes actin dynamics to
      initiate infection.

PMID- 22640597
TI  - Retinal image analysis aimed at blood vessel tree segmentation and early
      detection of neural-layer deterioration.
AB  - An automatic method of segmenting the retinal vessel tree and estimating status
      of retinal neural fibre layer (NFL) from high resolution fundus camera images is
      presented. First, reliable blood vessel segmentation, using 2D directional
      matched filtering, enables to remove areas occluded by blood vessels thus leaving
      remaining retinal area available to the following NFL detection. The local
      existence of rather faint and hardly visible NFL is detected by combining several
      newly designed local textural features, sensitive to subtle NFL characteristics,
      into feature vectors submitted to a trained neural-network classifier. Obtained
      binary retinal maps of NFL distribution show a good agreement with both medical
      expert evaluations and quantitative results obtained by optical coherence
      tomography.

PMID- 22640598
TI  - Ovarian cancer risk in postmenopausal women using estradiol-progestin therapy - a
      nationwide study.
AB  - OBJECTIVE: While previous data link the use of postmenopausal hormone therapy to
      an increased risk for ovarian cancer, little is known about the impact of various
      progestins, modes or routes of administration of hormone therapy for this risk.
      In this nationwide study, we compared relations between different estradiol
      progestin (EPT) formulations and epithelial ovarian cancer risk. METHODS: All
      Finnish women over 50 years using EPT for at least 6 months (224 015 women with
      602 ovarian cancers) during 1994-2006 were identified from the reimbursement
      register. The incidence of ovarian cancer in EPT users was compared to that in
      the age-matched background population by means of observed to expected ratio
      (standardized incidence ratio, SIR). RESULTS: Ovarian cancer risk was not
      elevated for EPT use of < 5 years but it was elevated for EPT use of >=5 years
      (SIR 1.21, 95% confidence interval (CI) 1.06-1.37). Medroxyprogesterone acetate
      and norethisterone acetate as components of EPT were associated with similar
      risks for use for >= 5 years (SIR 1.26, 95% CI 0.94-1.64 and SIR 1.42, 95% CI
      1.11-1.77, respectively). The risk did not differ between sequential or
      continuous EPT regimens or between oral or transdermal EPT formulations. The risk
      elevation for EPT use for >= 5 years was seen only for serous (SIR 1.56; 95% CI
      1.33-1.80) and mixed cancers (SIR 1.54; 95% CI 1.22-1.91), whereas the risk for
      mucinous cancer was decreased (SIR 0.47; 95% CI 0.22-0.86). CONCLUSION: The
      elevated risk of non-mucinous ovarian cancer in users of EPT >= 5 years does not
      depend on progestin type, mode or route of administration of EPT.

PMID- 22640599
TI  - Comparison of analyses of the XVth QTLMAS common dataset III: Genomic Estimations
      of Breeding Values.
AB  - BACKGROUND: The QTLMAS XVth dataset consisted of pedigree, marker genotypes and
      quantitative trait performances of animals with a sib family structure. Pedigree
      and genotypes concerned 3,000 progenies among those 2,000 were phenotyped. The
      trait was regulated by 8 QTLs which displayed additive, imprinting or epistatic
      effects. The 1,000 unphenotyped progenies were considered as candidates to
      selection and their Genomic Estimated Breeding Values (GEBV) were evaluated by
      participants of the XVth QTLMAS workshop. This paper aims at comparing the GEBV
      estimation results obtained by seven participants to the workshop. METHODS: From
      the known QTL genotypes of each candidate, two "true" genomic values (TV) were
      estimated by organizers: the genotypic value of the candidate (TGV) and the
      expectation of its progeny genotypic values (TBV). GEBV were computed by the
      participants following different statistical methods: random linear models
      (including BLUP and Ridge Regression), selection variable techniques (LASSO,
      Elastic Net) and Bayesian methods. Accuracy was evaluated by the correlation
      between TV (TGV or TBV) and GEBV presented by participants. Rank correlation of
      the best 10% of individuals and error in predictions were also evaluated. Bias
      was tested by regression of TV on GEBV. RESULTS: Large differences between
      methods were found for all criteria and type of genetic values (TGV, TBV). In
      general, the criteria ranked consistently methods belonging to the same family.
      CONCLUSIONS: Bayesian methods - A<B<C<Cpi - were the most efficient whatever the
      criteria and the True Value considered (with the notable exception of the MSEP of
      the TBV). The selection variable procedures (LASSO, Elastic Net and some
      adaptations) performed similarly, probably at a much lower computing cost. The
      TABLUP, which combines BayesB and GBLUP, generally did well. The simplest
      methods, GBLUP or Ridge Regression, and even worst, the fixed linear model, were
      much less efficient.

PMID- 22640600
TI  - Neurocognitive function impairment after whole brain radiotherapy for brain
      metastases: actual assessment.
AB  - Whole brain radiation therapy (WBRT) is an effective treatment in brain
      metastases and, when combined with local treatments such as surgery and
      stereotactic radiosurgery, gives the best brain control. Nonetheless, WBRT is
      often omitted after local treatment due to its potential late neurocognitive
      effects. Publications on radiation-induced neurotoxicity have used different
      assessment methods, time to assessment, and definition of impairment, thus making
      it difficult to accurately assess the rate and magnitude of the neurocognitive
      decline that can be expected. In this context, and to help therapeutic decision
      making, we have conducted this literature review, with the aim of providing an
      average incidence, magnitude and time to occurrence of radio-induced
      neurocognitive decline. We reviewed all English language published articles on
      neurocognitive effects of WBRT for newly diagnosed brain metastases or with a
      preventive goal in adult patients, with any methodology (MMSE, battery of
      neurcognitive tests) with which baseline status was provided. We concluded that
      neurocognitive decline is predominant at 4 months, strongly dependant on brain
      metastases control, partially solved at later time, graded 1 on a SOMA-LENT scale
      (only 8% of grade 2 and more), insufficiently assessed in long-term survivors,
      thus justifying all efforts to reduce it through irradiation modulation.

PMID- 22640601
TI  - Leaky ryanodine receptors in beta-sarcoglycan deficient mice: a potential common
      defect in muscular dystrophy.
AB  - BACKGROUND: Disruption of the sarcolemma-associated dystrophin-glycoprotein
      complex underlies multiple forms of muscular dystrophy, including Duchenne
      muscular dystrophy and sarcoglycanopathies. A hallmark of these disorders is
      muscle weakness. In a murine model of Duchenne muscular dystrophy, mdx mice,
      cysteine-nitrosylation of the calcium release channel/ryanodine receptor type 1
      (RyR1) on the skeletal muscle sarcoplasmic reticulum causes depletion of the
      stabilizing subunit calstabin1 (FKBP12) from the RyR1 macromolecular complex.
      This results in a sarcoplasmic reticular calcium leak via defective RyR1
      channels. This pathological intracellular calcium leak contributes to reduced
      calcium release and decreased muscle force production. It is unknown whether RyR1
      dysfunction occurs also in other muscular dystrophies. METHODS: To test this we
      used a murine model of Limb-Girdle muscular dystrophy, deficient in beta
      sarcoglycan (Sgcb-/-). RESULTS: Skeletal muscle RyR1 from Sgcb-/- deficient mice
      were oxidized, nitrosylated, and depleted of the stabilizing subunit calstabin1,
      which was associated with increased open probability of the RyR1 channels. Sgcb-/
      deficient mice exhibited decreased muscle specific force and calcium transients,
      and displayed reduced exercise capacity. Treating Sgcb-/- mice with the RyR
      stabilizing compound S107 improved muscle specific force, calcium transients, and
      exercise capacity. We have previously reported similar findings in mdx mice, a
      murine model of Duchenne muscular dystrophy. CONCLUSIONS: Our data suggest that
      leaky RyR1 channels may underlie multiple forms of muscular dystrophy linked to
      mutations in genes encoding components of the dystrophin-glycoprotein complex. A
      common underlying abnormality in calcium handling indicates that pharmacological
      targeting of dysfunctional RyR1 could be a novel therapeutic approach to improve
      muscle function in Limb-Girdle and Duchenne muscular dystrophies.

PMID- 22640602
TI  - Modified competing polymerase chain reaction primer for single tube quantitative
      PCR.
AB  - We developed a modified polymerase chain reaction (PCR) primer with 3' phosphate
      instead of hydroxyl group for single-tube accurate transcript quantification. 18S
      ribosomal RNA (rRNA) reference gene-specific modified primer was used for precise
      single-tube quantification of two target transcripts, namely chymotrypsin and
      jhamt (juvenile hormone acid methyl transferase) of Helicoverpa armigera. A
      comparative study of 3' phosphorylated primers, 3' mismatched primers, and
      commercial Competimers revealed that 3' phosphorylation was more efficient than
      the 3' mismatch and was on par with Competimers in blocking the primer extension.
      Thus, the modified primers can be used in single-tube, economical, and accurate
      PCR quantification of the target gene using any assay-specific reference gene.

PMID- 22640603
TI  - An electrophoretic approach to screen for glutamine deamidation.
AB  - Protein deamidation is a posttranslational modification with important
      implications in physiology and medicine. There is, however, no simple technique
      for a rapid screening of protein deamidation. The deamidating activity of
      transglutaminase was applied to establish a simple method for the screen of
      protein deamidation using recombinant human growth hormone, a rat hippocampal
      membrane fraction, and a cell homogenate enriched in 5-hydroxytryptamine-1A
      receptor as model systems. Here we report a simple, economic, and fast approach
      to assess protein deamidation by two electrophoretic methods: differential
      cleavage on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      via in situ V8 protease digestion and the principle of spot shifting via blue
      native (BN)-PAGE/two-dimensional (2D)-SDS-PAGE/immunoblotting.

PMID- 22640604
TI  - Identification and quantification of host cell protein impurities in
      biotherapeutics using mass spectrometry.
AB  - Residual host cell proteins (HCPs) in biotherapeutics can present potential
      safety risks to patients or compromise product stability. As such, their levels
      are typically monitored using a multicomponent HCP enzyme-linked immunosorbent
      assay (ELISA) to ensure adequate removal. However, it is not possible to
      guarantee ELISA coverage of every possible HCP impurity, and the specific HCPs
      remaining following purification are rarely identified. In the current study, we
      characterized the ability of an advanced two-dimensional liquid
      chromatography/mass spectrometry platform (2D-LC/MS(E)) to identify and quantify
      known low-level spiked protein impurities in a therapeutic peptide Fc fusion
      protein. The label-free quantification procedure based on the "top 3" intensity
      tryptic peptides per protein was applied and improved on for this application.
      Limits of detection for unknown HCPs were approximated from the spiked protein
      data along with estimates for the quantitative accuracy of the method. In all, we
      established that most protein impurities present at 13+/-4ppm can be identified
      with a quantitative error of less than 2-fold using the more sensitive of two
      tested method formats. To conclude the study, we characterized all detectable
      Escherichia coli proteins present in this Fc fusion protein drug substance and
      discuss future applications of the method.

PMID- 22640605
TI  - Neurohormones and sleep.
AB  - Mutual interactions between neurohormones, sleep, and the circadian system have
      been extensively studied. Hormonal secretion is either influenced by sleep and is
      independent of circadian timing or is closely coupled with the light-dark cycle,
      although both processes ultimately interact with each other. Sleep has a strong
      effect on the levels of some hormones (e.g., growth hormone) but little effect on
      others that are primarily regulated by the circadian system (e.g., melatonin).
      The exact mechanisms through which sleep affects circulating hormonal levels are
      not well understood. Much more is known about how the circadian system influences
      the secretion of hormones. Under normal circumstances, behaviors and the
      circadian system are synchronized with an optimal phase relationship, and
      consequently, hormonal systems are exquisitely regulated. Every bit of
      information constitutes but one small component of a broader, more global
      neurohormonal picture. In this review, we attempt to divide this analysis into
      sections including the pineal gland, adenohypophysis, neurohypophysis, describing
      the reciprocal influence regarding sleep and various neurohormones.

PMID- 22640606
TI  - The role of orexin/hypocretin in the central nervous system and peripheral
      tissues.
AB  - Orexin, also called hypocretin, is a neuropeptide produced in neurons sparsely
      distributed in the lateral hypothalamic area. Orexin exhibits its physiological
      effects after binding two G-protein-coupled receptors, orexin 1 receptor and
      orexin 2 receptor. Impairment of the orexin signal, either by deletion of the
      prepro-orexin or orexin 2 receptor gene or by the ablation of orexin neurons,
      results in a sleep disorder similar to narcolepsy, suggesting that the orexin
      system plays an important role in the regulation of sleep/wakefulness. In
      addition, previous studies have suggested that orexin is involved in energy and
      fluid homeostasis, emotion regulation, stress responsiveness, and reward.
      However, growing evidence also suggests that orexin affects the function of
      peripheral tissues via direct activation of orexin receptors or through
      activation of autonomic nervous or endocrine systems. In this review, we discuss
      the physiological roles of orexin not only in the central nervous system but also
      in the peripheral tissues.

PMID- 22640607
TI  - Plasticity in neurons synthesizing wake/arousal promoting hormone
      hypocretin/orexin.
AB  - The hypothalamus is a critical brain structure regulating physiological functions
      essential to the survival of individuals and species. One of the striking
      characteristics of this brain region is the abundance of nerve cells (neurons)
      expressing a great numbers of neurotransmitters and neuromodulators, among which
      are hormones released into the blood stream through brain neuroendocrinological
      routes. The neurons in the lateral hypothalamus take part in intra- and
      extrahypothalamic circuits controlling basic physiological functions essential
      for the well being of animal bodies (such as cardiovascular function, respiratory
      function, immune responses, etc.), animal behaviors required for the maintenance
      of the survival of individuals (food foraging, flight, fight, etc.) and species
      (reproductive function), and higher brain functions (learning and memory, mental
      state, etc.). Hypocretin (also called orexin) comprises of two neuropeptides
      exclusively synthesized by neurons in the perifornical/lateral hypothalamus.
      Although hypocretin/orexin was initially found to enhance food intake, it is now
      clear that the functions mediated by hypocretin/orexin are well beyond what were
      originally proposed. Specifically, hypocretin/orexin is a crucial promoter of
      wakefulness; deficiency in the hypocretin/orexin system leads to diseases and
      disorders such as narcolepsy. It is clear that neurons synthesizing
      hypocretin/orexin are consistently under regulation originating from various
      parts of the brain and that the status of activity in hypocretin/orexin neurons
      is closely related with the nutritional and behavioral state of animals.
      Therefore, the demand to make adaptive changes in hypocretin/orexin neurons to
      accommodate the changes in the external environment and behavioral state of
      animals is expected. The latest developments in the studies of plasticity in
      hypocretin/orexin neurons under the challenges from environmental and behavioral
      factors have dramatically shaped the understanding of the roles of
      hypocretin/orexin neurons in the maintenance of the survival of animals. More
      importantly, the studies of plasticity in hypocretin/orexin neurons as the
      consequence of physiological, behavioral, and environmental challenges may shed
      new insight on the understanding and treatment of sleep disorders (such as
      insomnia).

PMID- 22640608
TI  - Expression of orexin receptors in the pituitary.
AB  - Orexin receptors type 1 (OX1R) and type 2 (OX2R) are G protein-coupled receptors
      whose structure is highly conserved in mammals. OX1R is selective for orexin A,
      and OX2R binds orexin A and orexin B with similar affinity. Orexin receptor
      expression was observed in human, rat, porcine, sheep as well as Xenopus laevis
      pituitaries, both in the adenohypophysis and in the neurohypophysis. The
      expression level is regulated by gonadal steroid hormones and GnRH. The majority
      of orexins reaching the pituitary originate from the lateral hypothalamus, but
      due to the presence of the receptors and the local production of orexins in the
      pituitary, orexins could deliver an auto/paracrine effect within the gland.
      Cumulative data indicate that orexins are involved in the regulation of LH, GH,
      PRL, ACTH, and TSH secretion by pituitary cells, pointing to orexins' effect on
      the functioning of the endocrine axes. Those hormones may also serve as a signal
      linking metabolic status with endocrine control of sleep, arousal, and
      reproduction processes.

PMID- 22640609
TI  - Transcriptional regulation of the hypocretin/orexin gene.
AB  - The hypocretin (also known as orexin) system reacts to environmental changes in
      the internal milieu (pH, glucose, and various hormones) and the external
      environment (activity, fasting, and sleep deprivation) and regulates various
      physiological functions. Several feedback mechanisms, such as those listed above,
      have been reported to regulate the hypocretin system even at the transcriptional
      level. In addition, some transcription factors, such as forkhead box A2; nuclear
      receptor subfamily 6, group A, member 1; and early B-cell factor 2, were
      determined to be regulators of the preprohypocretin gene. However, little is
      known concerning the specific components that react to environmental changes and
      the determinants of spatial expression of the hypocretin gene within the lateral
      hypothalamus. This review focuses on the recent findings of transcription factors
      that regulate preprohypocretin transcription in addition to discussing the future
      prospects for transcriptional regulation of the hypocretin gene.

PMID- 22640611
TI  - Orexins: tissue localization, functions, and its relation to insulin secretion
      and diabetes mellitus.
AB  - Orexins play a role in many biological functions include sleep, feeding, and
      energy balance. They also regulate circadian rhythms and the way that we feel
      pain. Orexins have been identified in a variety of tissues including the
      cerebrospinal fluid, blood, hypothalamus, spinal cord, sensory ganglion, enteric
      nervous system, pituitary, adrenal, salivary and lacrimal glands, testis,
      vestibular gland, and skin. Orexins play a role in a variety of biological
      functions including arousal, sleeping, food and fluid intake, pain, memory,
      perception of odor, and sexual activity. Orexins have also been implicated in the
      regulation of glucose metabolism. The expression of orexin is induced by
      hypoglycemia, low food, pregnancy, and hemodialysis. In contrast, factors that
      inhibit the expression of orexins include obstructive sleep apnea, aging,
      depression, obesity, traumatic brain injury, and inflammatory molecules such as
      liposaccharide. In conclusion, orexins are widely distributed and involved in a
      large variety of biological activities.

PMID- 22640612
TI  - Orexin neurons and emotional stress.
AB  - Stress increases cardiac function, ventilation, and body temperature and induces
      analgesia. These changes, which result in an increase in metabolic rate, oxygen
      supply, and the conduction velocity of nerve impulses, prepare the body for a
      fight-or-flight response. A part of the hypothalamus called the defense area has
      long been known to play a key role in these responses, but the precise mechanisms
      are largely unknown. Our recent findings suggest that orexin (hypocretin) neurons
      act as a master switch of the fight-or-flight response. In addition, our results,
      as well as those from other researchers, suggest that orexin neurons do not
      modulate specific behaviors such as the fight-or-flight responses but rather
      integrate the autonomic functions and behaviors in a broad sense or in a
      vigilance state-dependent manner. The orexin system seems to be a pivotal link
      between the subconscious and the conscious brain functions.

PMID- 22640610
TI  - Energy expenditure: role of orexin.
AB  - The orexins/hypocretins are endogenous, modulatory and multifunctional
      neuropeptides with prominent influence on several physiological processes. The
      influence of orexins on energy expenditure is highlighted with focus on orexin
      action on individual components of energy expenditure. As orexin stabilizes and
      maintains normal states of arousal and the sleep/wake cycle, we also highlight
      orexin mediation of sleep and how sleep interacts with energy expenditure.

PMID- 22640613
TI  - Orexin and central regulation of cardiorespiratory system.
AB  - The hypothalamic peptide orexin plays a role in many physiological systems
      including feeding behavior, sleep-wakefulness, reward system, stress, and
      nociception. In addition, it is now clear that orexin is involved in the central
      regulation of cardiorespiratory function. Here, we review the cardiorespiratory
      effects elicited by central orexin and consider the physiological role of this
      peptide in central cardiorespiratory control in normal and pathophysiological
      states. Orexin neurons are found exclusively in the hypothalamus but project to
      almost all brain regions including cardiorespiratory regulatory areas, where
      their receptors are also expressed. Administration of orexin into the nucleus
      tractus solitarius, rostral ventrolateral medulla, rostral ventromedial medulla,
      and spinal cord increases blood pressure, heart rate, and sympathetic nerve
      activity. Orexin neurons stimulate respiration and are sensitive to changes in
      pH. Orexin knockout mice have apnoeic episodes in sleep. Therefore, orexin may be
      a potentially important therapeutic target for the treatment of cardiorespiratory
      disorders.

PMID- 22640615
TI  - Glutamate and orexin neurons.
AB  - Orexin neurons are localized in the lateral hypothalamus and regulate many
      functions including sleep-wake states. Substantial number of neurotransmitters
      and neuromodulators has been proposed to influence orexinergic system. Glutamate,
      as the major excitatory amino acid neurotransmitter in the hypothalamus, was
      shown to mediate orexin neurons in the regulation of wakefulness and feeding.
      Glutamate is readily present in the lateral hypothalamus, and glutamate receptors
      are expressed by the neurons of this region. Glutamate agonists initiate
      excitatory postsynaptic currents in orexin neurons, and this can be blocked by
      specific antagonists of the glutamate receptors. It is reported that both NMDA
      and non-NMDA receptors contribute the glutamatergic neurotransmission which
      affects orexinergic functions. Glutamatergic axon terminals are demonstrated to
      make contacts with the orexin neurons, as revealed by the presence of vesicular
      glutamate transporter proteins in the terminals, and these contacts were
      ultrastructurally confirmed to establish synapses on orexin neurons. This chapter
      reviews the literature on the glutamatergic regulation of orexin neurons
      including the data from our laboratory.

PMID- 22640616
TI  - Serotonin conflict in sleep-feeding.
AB  - Short sleep duration has been suggested to be a risk factor for weight gain and
      adiposity. Serotonin (5-HT) substantially contributes to the regulation of sleep
      and feeding behavior. Although 5-HT predominately promotes waking and satiety,
      the effects of 5-HT depend on 5-HT receptor function. The 5-HT1A, 5-HT1B, 5-HT2A,
      5-HT2C, 5-HT6, and 5-HT7 receptors reportedly contribute to sleep-waking
      regulation, whereas the 5-HT1B and 5-HT2C receptors contribute to the regulation
      of satiety. The 5-HT1B and 2C receptors may therefore be involved in the
      regulation of sleep-feeding. In genetic studies, 5-HT1B receptor mutant mice
      display greater amounts of rapid eye movement sleep (REMS) than wild-type mice,
      while displaying no effects on waking or slow wave sleep (SWS). On the other
      hand, 5-HT2C receptor mutant mice exhibit increased wakefulness and decreased
      SWS, without any effect on REMS. Moreover, the 5-HT2C receptor mutants display
      leptin-independent hyperphagia, leading to a middle-aged onset of obesity,
      whereas 5-HT1B receptor mutants do not display any effect on food intake. Thus,
      the genetic deletion of 5-HT2C receptors results in sleep loss-associated
      hyperphagia, leading to the late onset of obesity. This is a quite different
      pattern of sleep-feeding behavior than is observed in disturbed leptin signaling,
      which displays an increase in sleep-associated hyperphagia. In pharmacologic
      studies, 5-HT1B and 5-HT2C receptors upregulate wakefulness and downregulate SWS,
      REMS, and food intake. These findings suggest that 5-HT1B/2C receptor stimulation
      induces sleep loss-associated anorexia. Thus, the central 5-HT regulation of
      sleep-feeding can be dissociated. Functional hypothalamic proopiomelanocortin and
      orexin activities may contribute to the dissociated 5-HT regulation.

PMID- 22640614
TI  - Hypocretin/orexin involvement in reward and reinforcement.
AB  - Since the discovery of the hypocretins/orexins, a series of observations have
      indicated that these peptides influence a variety of physiological processes
      including feeding, sleep/wake function, memory, and stress. More recently, the
      hypocretins have been implicated in reinforcement and reward-related processes
      via actions on the mesolimbic dopamine system. Although investigation into the
      relationship between the hypocretins and reinforcement/reward remains in
      relatively early stages, accumulating evidence suggests that continued research
      into this area may offer new insights into the addiction process and provide the
      foundation to generate novel pharmacotherapies for drug abuse. The current
      chapter will focus on contemporary perspectives of hypocretin regulation of
      cocaine reward and reinforcement via actions on the mesolimbic dopamine system.

PMID- 22640618
TI  - Action of modafinil through histaminergic and orexinergic neurons.
AB  - Modafinil is a wake-promoting drug used for the treatment of excessive daytime
      sleepiness due to narcolepsy as well as excessive sleepiness associated with
      obstructive sleep apnea and shift work disorder. Although the wake-promoting
      effect of modafinil is expressed through the dopaminergic and the
      norepinephrinergic systems similar to that of classical psychostimulants, the
      mechanism of action is distinct from those compounds in terms of the involvement
      of the histaminergic and the orexinergic systems. Modafinil activates the
      histaminergic system in an indirect manner, presumably via attenuation of the
      inhibitory GABAergic input to the histaminergic neurons. The orexinergic system
      controls arousal through the histaminergic system, and the modafinil-induced
      increment of histamine release is abolished in orexin neuron-ablated mice,
      suggesting that modafinil increases histaminergic tone via orexinergic neurons.
      Clinical and experimental investigations have suggested less importance of the
      orexinergic system in the wake-promoting effect of modafinil, but the orexinergic
      system is considered to be involved in modafinil-induced alertness or synaptic
      plasticity.

PMID- 22640619
TI  - Anti-Parkinson drugs and orexin neurons.
AB  - Non-ergot-type dopamine receptor agonists such as ropinirole are used for
      treatment of Parkinson disease, but they frequently produce adverse actions
      characterized by sleepiness and sleep attacks. Because these symptoms are similar
      to those observed in patients with narcolepsy, a sleep disorder caused by
      degeneration of hypothalamic orexin neurons, involvement of orexinergic system in
      the adverse drug actions is suspected. We found that ropinirole and other non
      ergot dopamine D2 receptor agonists cause selective loss of orexin-immunoreactive
      neurons in organotypic slice culture of rat hypothalamus. The mechanism of this
      action is considered to involve D2 receptor-mediated presynaptic suppression of
      glutamatergic excitatory inputs to orexin neurons because continuous silencing of
      excitatory activity of orexin neurons can deplete orexin from cell bodies. In
      addition, Parkinson disease itself may accompany loss of orexin neurons.
      Disturbance of orexinergic system may play an important role in sleep/arousal
      dysfunctions under these and other clinical conditions.

PMID- 22640617
TI  - Humoral sleep regulation; interleukin-1 and tumor necrosis factor.
AB  - Two substances, the cytokines interleukin-1 beta (IL1beta) and tumor necrosis
      factor alpha (TNFalpha), known for their many physiological roles, for example,
      cognition, synaptic plasticity, and immune function, are also well characterized
      in their actions of sleep regulation. These substances promote non-rapid eye
      movement sleep and can induce symptoms associated with sleep loss such as
      sleepiness, fatigue, and poor cognition. IL1beta and TNFalpha are released from
      glia in response to extracellular ATP. They bind to their receptors on neurons
      resulting in neuromodulator and neurotransmitter receptor up/downregulation
      (e.g., adenosine and glutamate receptors) leading to altered neuronal
      excitability and function, that is, a state change in the local network.
      Synchronization of state between local networks leads to emergent whole brain
      oscillations, such as sleep/wake cycles.

PMID- 22640620
TI  - Cocaine and nicotine research illustrates a range of hypocretin mechanisms in
      addiction.
AB  - Hypocretins (also known as orexins) are neuropeptides synthesized in the lateral
      hypothalamus and perifornical region and projecting widely throughout the brain.
      They play an important modulatory role in plasticity related to addictive
      behavior. Hypocretin signaling to the ventral tegmental area (VTA) promotes
      synaptic plasticity by potentiating glutamatergic inputs to dopamine neurons and
      is required for the plasticity induced by stimulant drugs like cocaine.
      Plasticity in the VTA leads to increased output of dopamine neurons and increased
      release of dopamine in projection areas, which is associated with the development
      of addiction-related behaviors. Antagonists of hypocretin receptors inhibit some
      of these behaviors, particularly those with high effort requirements, suggesting
      a significant role of hypocretin in the motivation to obtain drugs. Furthermore,
      hypocretin neurons are also targeted by drugs of abuse, such as nicotine.
      Projections of hypocretin neurons to regions beyond the VTA may also play a
      significant role in motivation and addiction. Taken together, the hypocretin
      system may be a prime drug target for treatment of addiction and related
      disorders.

PMID- 22640621
TI  - Sleep and orexins in nonmammalian vertebrates.
AB  - Although a precise definition of "sleep" has yet to be established, sleep-like
      behaviors have been observed in all animals studied to date including mammals and
      nonmammalian vertebrates. Orexins are hypothalamic neuropeptides that are
      involved in the regulation of many physiological functions, including feeding,
      thermoregulation, cardiovascular control, as well as the control of the sleep
      wakefulness cycle. To date, the knowledge on the functions of orexins in
      nonmammalian vertebrates is still limited, but the similarity of the structures
      of orexins and their receptors among vertebrates suggest that they have similar
      conserved physiological functions. This review describes our current knowledge on
      sleep in nonmammalian vertebrates (birds, reptiles, amphibians, and fish) and the
      possible role of orexins in the regulation of their energy homeostasis and
      arousal states.

PMID- 22640622
TI  - Orexin system in teleost fish.
AB  - Orexin is a neuropeptide distributed widely among vertebrates. In mammals, orexin
      and its receptor system are involved in the regulation of food intake,
      locomotion, and psychomotor activities including the sleep/wakefulness cycle.
      With regard to nonmammalian vertebrates, there has also been intensive study
      aimed at the identification and functional characterization of orexin and its
      receptor, and recent investigations of the role of orexin have revealed that it
      exerts behavioral effects in teleost fish. Goldfish and zebrafish are excellent
      teleost fish models, and in these species it has been demonstrated that orexin
      increases food consumption as an orexigenic factor and enhances locomotor
      activity, as well as being involved in the regulation of active and rest status
      (circadian rhythmicity and the sleep/wakefulness cycle), as is the case in
      mammals. This chapter reviews current knowledge of orexin derived from studies of
      teleost fish, as representative nonmammals, focusing particularly on the role of
      the orexin system, and examines its significance from a comparative viewpoint.

PMID- 22640623
TI  - Sleep hormones. Preface.

PMID- 22640624
TI  - Solid neuroendocrine breast carcinoma: mammographic and sonographic features in
      thirteen cases.
AB  - This study aimed to determine and quantitate the mammographic and sonographic
      characteristics in 13 cases of solid neuroendocrine breast carcinoma (NEBC) and
      to analyze the association of radiological findings with the clinical and
      histopathologic findings. The clinical data and imaging findings of 13 female
      patients with histologically confirmed solid NEBC were reviewed. Imaging data
      were evaluated by two radiologists for a consensual diagnosis. All patients
      presented with one palpable mass; only 1 experienced occasional breast pain, and
      5 complained of fluid discharge. In 7 patients, the masses were firm and mobile.
      Regional lymph node metastasis was noted in only 1 patient. For the 10 patients
      who underwent mammography, 6 had a mass, 1 had clustered small nodules with
      clustered punctuate microcalcifications, 2 had asymmetric focal density, and 1
      had solitary punctuate calcification. Most of the masses had irregular shape with
      indistinct or microlobulated margins. For the 9 patients who underwent
      ultrasonography (US), 9 masses were depicted, all of which were hypoechoic,
      mostly with irregular shape and without acoustic phenomena. Different types of
      acoustic phenomena were also identified. One patient had developed distant
      metastases during follow-up. NEBC has a variety of presentations, but it is
      mostly observed on mammograms as a dense, irregular mass with indistinct or
      microlobulated margins. Sonographically, it typically presents as an irregular,
      heterogeneously hypoechoic mass with normal sound transmission. Histories of
      nipple discharge and calcification observed using imaging are not rare.

PMID- 22640625
TI  - Dose-volume parameters and clinical outcome of CT-guided free-hand high-dose-rate
      interstitial brachytherapy for cervical cancer.
AB  - Currently, image-based 3-dimentional (3D) planning brachytherapy allows for a
      better assessment of gross tumor volume (GTV) and the definition and delineation
      of target volume in cervix cancer. In this study, we investigated the feasibility
      of our novel computed tomography (CT)-guided free-hand high-dose-rate
      interstitial brachytherapy (HDRISBT) technique for cervical cancer by evaluating
      the dosimetry and preliminary clinical outcome of this approach. Dose-volume
      histogram (DVH) parameters were analyzed according to the Gynecological GEC-ESTRO
      Working Group recommendations for image-based 3D treatment in cervical cancer.
      Twenty cervical cancer patients who underwent CT-guided free-hand HDRISBT between
      March 2009 and June 2010 were studied. With a median of 5 (range, 4-7) implanted
      needles for each patient, the median dose of brachytherapy alone delivered to 90%
      of the target volume (D90) was 45 (range, 33-54) Gyalpha/beta10 for high-risk
      clinical target volume (HR-CTV) and 30 (range, 20-36) Gyalpha/beta10 for
      intermediate-risk clinical target volume (IR-CTV). The percentage of the CTV
      covered by the prescribed dose (V100) of HR-CTV with brachytherapy alone was
      81.9%-99.2% (median, 96.7%). With an additional dose of external beam
      radiotherapy (EBRT), the median D90 was 94 (range, 83-104) Gyalpha/beta10 for HR
      CTV and 77 (range, 70-87) Gyalpha/beta10 for IR-CTV; the median dose delivered to
      100% of the target volume (D100) was 75 (range, 66-84) Gyalpha/beta10 for HR-CTV
      and 65 (range, 57-73) Gyalpha/beta10 for IR-CTV. The minimum dose to the most
      irradiated 2 cc volume (D2cc) was 73-96 (median, 83) Gyalpha/beta3 for the
      bladder, 64-98 (median, 73) Gyalpha/beta3 for the rectum, and 52-69 (median, 61)
      Gyalpha/beta3 for the sigmoid colon. After a median follow-up of 15 months
      (range, 3-24 months), two patients experienced local failure, and 1 showed
      internal iliac nodal metastasis. Despite the relatively small number of needles
      used, CT-guided HDRISBT for cervical cancer showed favorable DVH parameters and
      clinical outcome.

PMID- 22640626
TI  - Chemical proteomics: terra incognita for novel drug target profiling.
AB  - The growing demand for new therapeutic strategies in the medical and pharmaceutic
      fields has resulted in a pressing need for novel druggable targets.
      Paradoxically, however, the targets of certain drugs that are already widely used
      in clinical practice have largely not been annotated. Because the pharmacologic
      effects of a drug can only be appreciated when its interactions with cellular
      components are clearly delineated, an integrated deconvolution of drug-target
      interactions for each drug is necessary. The emerging field of chemical
      proteomics represents a powerful mass spectrometry (MS)-based affinity
      chromatography approach for identifying proteome-wide small molecule-protein
      interactions and mapping these interactions to signaling and metabolic pathways.
      This technique could comprehensively characterize drug targets, profile the
      toxicity of known drugs, and identify possible off-target activities. With the
      use of this technique, candidate drug molecules could be optimized, and
      predictable side effects might consequently be avoided. Herein, we provide a
      holistic overview of the major chemical proteomic approaches and highlight recent
      advances in this area as well as its potential applications in drug discovery.

PMID- 22640628
TI  - The favorable impact of PIK3CA mutations on survival: an analysis of 2587
      patients with breast cancer.
AB  - The phosphatidylinositol-3 kinase(PI3K) pathway regulates a number of cellular
      processes, including cell survival, cell growth, and cell cycle progression.
      Consequently, this pathway is commonly deregulated in cancer. In particular,
      mutations in the gene PIK3CA that encodes the p110alpha catalytic subunit of the
      PI3K enzymes result in cell proliferation and resistance to apoptosis in vitro
      and induce breast tumors in transgenic mice. These data underscore the role of
      this pathway during oncogenesis. Thus, an ongoing, large-scale effort is underway
      to develop clinically active drugs that target elements of the PI3K pathway.
      However, conflicting data suggest that gain-of-function PIK3CA mutations may be
      associated with either a favorable or a poor clinical outcome, compared with the
      wild-type PIK3CA gene. In the current study, we performed a systematic review of
      breast cancer clinical studies.  Upon evaluation of 2587 breast cancer cases from
      12 independent studies, we showed that patients with tumors harboring a PIK3CA
      mutation have a better clinical outcome than those with a wild-type PIK3CA gene.
      Importantly, this improved prognosis may pertain only to patients with mutations
      in the kinase domain of p110alpha and to postmenopausal women with estrogen
      receptor-positive breast cancer. We propose three potential explanations for this
      paradoxical observation. First, PIK3CA mutations may interfere with the
      metastasis process or may induce senescence, which results in a better outcome
      for patients with mutated tumors. Secondly, we speculate that PIK3CA mutations
      may increase early tumor diagnosis by modification of the actin cytoskeleton in
      tumor cells. Lastly, we propose that PIK3CA mutations may be a favorable
      predictive factor for response to hormonal therapy, giving a therapeutic
      advantage to these patients. Ultimately, an improved understanding of the
      clinical impact of PIK3CA mutations is critical for the development of optimally
      personalized therapeutics against breast cancer and other solid tumors. This
      effort will be important to prevent or explain therapeutic failures and select
      patients who are most likely to respond to new therapies that inhibit the PI3K
      pathway.

PMID- 22640627
TI  - R-CHOP regimen can significantly decrease the risk of disease relapse and
      progression in patients with non-germinal center B-cell subtype diffuse large B
      cell lymphoma.
AB  - To further explore the role of rituximab when added to the CHOP-like regimen in
      the treatment of immunohistochemically defined non-germinal center B-cell subtype
      (non-GCB) diffuse large B-cell lymphoma(DLBCL), 159 newly diagnosed DLBCL
      patients were studied retrospectively based on the immunohistochemical evaluation
      of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP
      like regimen, and rituximab was added for the other 49 patients. Cox regression
      analysis showed that compared with the CHOP-like regimen, the rituximab-based
      regimen(R-CHOP regimen) significantly decreased the risk of disease relapse and
      progression in CD10-negative patients (P=0.001), Bcl-6-negative patients
      (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in
      patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients
      with the opposite immunohistochemical marker expression profile and GCB subtype
      did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB
      subtype patients had a significantly higher expression rate of Bcl-2 than GCB
      subtype patients (P=0.042). Although univariate analysis found that both Bcl-2
      positive and -negative patients had significantly higher event-free survival
      rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained
      significance in the Cox regression analysis. We conclude that the addition of
      rituximab can significantly improve the prognosis of patients with non-GCB
      subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1,
      and Bcl-2.

PMID- 22640629
TI  - Association between genetic variations in tumor necrosis factor receptor genes
      and survival of patients with T-cell lymphoma.
AB  - The prognosis of T-cell lymphoma (TCL) has been shown to be associated with the
      clinical characteristics of patients. However, there is little knowledge of
      whether genetic variations also affect the prognosis of TCL. This study
      investigated the associations between single nucleotide polymorphisms(SNPs) in
      tumor necrosis factor receptor superfamily(TNFRSF) genes and the survival of
      patients with TCL. A total of 38 tag SNPs in 18 TNFRSF genes were genotyped using
      Sequenom platform in 150 patients with TCL. Kaplan-Meier survival estimates were
      plotted and significance was assessed using log-rank tests. Cox proportional
      hazard models were used to analyze each of these 38 SNPs with adjustment for
      covariates that might influence patient survival, including sex and international
      prognostic Index score. Hazard ratios (HRs) and their 95% confidence
      intervals(CIs) were calculated. Among the 38 SNPs tested, 3 were significantly
      associated with the survival of patients with TCL. These SNPs were located at
      LTbetaR (rs3759333C>T) and TNFRSF17(rs2017662C>T and rs2071336C>T). The 5-year
      survival rates were significantly different among patients carrying different
      genotypes and the HRs for death between the different genotypes ranged from 0.45
      to 2.46. These findings suggest that the SNPs in TNFRSF genes might be important
      determinants for the survival of TCL patients.

PMID- 22640630
TI  - Serum glucuronoxylomannan may be more appropriate for the diagnosis and
      therapeutic monitoring of Trichosporon fungemia than serum beta-D-glucan.

PMID- 22640631
TI  - mGlu2/3 and mGlu5 receptors: potential targets for novel antidepressants.
AB  - Major depressive disorder is among the most prevalent forms of mental illness.
      All currently available antidepressant medications have stemmed from study of the
      mechanisms of serendipitously discovered drugs, and only 30-50% of patients
      exhibit remission and frequently at least 3-4 weeks are required for
      manifestation of significant therapeutic effects. To overcome these drawbacks,
      discovering novel neuronal mechanisms of pathophysiology of depression as well as
      more effective treatments are necessary. This review focuses on the metabotropic
      glutamate (mGlu) receptors and their potential for drug targets for the treatment
      of depression. In particular, accumulating evidence has indicated the potential
      importance and usefulness of agents acting on mGlu2/3 and mGlu5 receptors.
      Preclinical and clinical evidence of mGlu2/3 receptor ligands and mGlu5 receptor
      antagonists are described. Moreover, their potential in clinic will be discussed
      in the context of neuronal mechanisms of ketamine, an agent recently demonstrated
      a robust effect for patients with treatment-resistant depression. This article is
      part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.

PMID- 22640632
TI  - Targeting metabotropic glutamate receptors in neuroimmune communication.
AB  - L-Glutamate (L-Glu) is the principal excitatory neurotransmitter in the Central
      Nervous System (CNS), where it regulates cellular and synaptic activity, neuronal
      plasticity, cell survival and other relevant functions. Glutamatergic
      neurotransmission is complex and involves both ionotropic (ligand-gated ion
      channels; iGluRs) and metabotropic receptors (G-protein coupled receptors).
      Recent evidence suggests that glutamatergic receptors are also expressed by
      immune cells, regulating the degree of cell activation. In this review we
      primarily focus on mGluRs and their role in the crosstalk between the central
      nervous and immune systems during neuroinflammation.

PMID- 22640633
TI  - Age-Dependent Neuroimmune Modulation of IGF-1R in the Traumatic Mice.
AB  - BACKGROUND: Age-dependent neuroimmune modulation following traumatic stress is
      accompanied by discordant upregulation of Fyn signaling in the frontal cortex,
      but the mechanistic details of the potential cellular behavior regarding IGF
      1R/Fyn have not been established. METHODS: Trans-synaptic IGF-1R signaling during
      the traumatic stress was comparably examined in wild type, Fyn (-/-) and MOR (-/
      ) mice. Techniques included primary neuron culture, in vitro kinase activity,
      immunoprecipitation, Western Blot, sucrose discontinuous centrifugation. Besides
      that, [3 H] incorporation was used to assay lymphocyte proliferation and NK cell
      activity. RESULTS: We demonstrate robust upregulation of synaptic Fyn activity
      following traumatic stress, with higher amplitude in 2-month mice than that in 1
      year counterpart. We also established that the increased Fyn signaling is
      accompanied by its molecular connection with IGF-1R within the synaptic zone.
      Detained analysis using Fyn (-/-) and MOR (-/-) mice reveal that IGF-1R/Fyn
      signaling is governed to a large extent by mu opioid receptor (MOR), and with age
      dependent manner; these signaling cascades played a central role in the
      modulation of lymphocyte proliferation and NK cell activity. CONCLUSIONS: Our
      data argued for a pivotal role of synaptic IGF-1R/Fyn signaling controlled by MOR
      downstream signaling cascades were crucial for the age-dependent neuroimmune
      modulation following traumatic stress. The result here might present a new
      quality of synaptic cellular communication governing the stress like events and
      have significant potential for the development of therapeutic approaches designed
      to minimize the heightened vulnerability during aging.

PMID- 22640634
TI  - Bacillus thuringiensis Cry3Aa protoxin intoxication of Tenebrio molitor induces
      widespread changes in the expression of serine peptidase transcripts.
AB  - The yellow mealworm, Tenebrio molitor, is a pest of stored grain products and is
      sensitive to the Bacillus thuringiensis (Bt) Cry3Aa toxin. As digestive
      peptidases are a determining factor in Cry toxicity and resistance, we evaluated
      the expression of peptidase transcripts in the midgut of T. molitor larvae fed
      either a control or Cry3Aa protoxin diet for 24 h (RNA-Seq), or in larvae exposed
      to the protoxin for 6, 12, or 24 h (microarrays). Cysteine peptidase transcripts
      (9) were similar to cathepsins B, L, and K, and their expression did not vary
      more than 2.5-fold in control and Cry3Aa-treated larvae. Serine peptidase
      transcripts (48) included trypsin, chymotrypsin and chymotrypsin-like, elastase 1
      like, and unclassified serine peptidases, as well as homologs lacking functional
      amino acids. Highly expressed trypsin and chymotrypsin transcripts were severely
      repressed, and most serine peptidase transcripts were expressed 2- to 15-fold
      lower in Cry3Aa-treated larvae. Many serine peptidase and homolog transcripts
      were found only in control larvae. However, expression of a few serine peptidase
      transcripts was increased or found only in Cry3Aa-treated larvae. Therefore, Bt
      intoxication significantly impacted the expression of serine peptidases,
      potentially important in protoxin processing, while the insect maintained the
      production of critical digestive cysteine peptidases.

PMID- 22640635
TI  - Pulmonary atresia with intact septum: the use of Conquest Pro coronary guidewire
      for perforation of atretic valve and subsequent interventions.
AB  - OBJECTIVE: To determine the feasibility and safety of the Conquest Pro wire as an
      alternative to radiofrequency wire for perforation of atretic pulmonary valve and
      subsequent balloon dilatation and patent ductus arteriosus stenting in patients
      with pulmonary atresia with intact ventricular septum. BACKGROUND: Radiofrequency
      valvotomy and balloon dilatation has become the standard of care for pulmonary
      atresia with intact ventricular septum in many institutions today. METHODS: We
      report eight consecutive patients in whom we used the Conquest Pro coronary
      guidewire, a stiff wire normally reserved for revascularisation of coronary
      lesions with chronic total occlusion, for perforation of atretic pulmonary valve
      and subsequent balloon dilatation, and stenting of the patent ductus arteriosus.
      RESULTS: Perforation of atretic pulmonary valve was successful in seven out of
      eight cases. Radiofrequency valvotomy was employed after failure of perforation
      by the Conquest Pro wire in one case where the right ventricular outflow tract
      was broad based and tapered towards the pulmonary valve, and was heavily
      trabeculated. Failure of the Conquest Pro wire to perforate the pulmonary valve
      plate was mainly attributed by the failure to engage the wire at the correct
      position. CONCLUSION: The Conquest Pro wire for perforation and subsequent
      interventions in the more straightforward cases of pulmonary atresia with intact
      ventricular septum is effective and safe, simplifying the entire procedure.
      However, the radiofrequency generator and wires remain essential tools in the
      paediatric interventional catheter laboratory.

PMID- 22640636
TI  - Post-traumatic stress symptoms in mothers of children with leukaemia undergoing
      the first 12 months of therapy: predictive models.
AB  - The aim of this study consists in the measurement of psychological health and
      adaptation in mothers of children during the first 12 months of treatment for
      leukaemia and in the identification of possible early predictors. Ninety-four
      mothers were followed longitudinally at one week (T1), one month (T2), six months
      (T3) and 12 months (T4) post-diagnosis. The instruments used were: PTSD symptom
      checklist, BSI-18, Problem Scale, Ladder of life and an in-depth interview (EFI
      C). Couple connectedness, family routine reorganisation, parental communication
      around the child's illness and trust in the medical care significantly increased
      from T1 to T4. Two models are proposed concerning possible predictors of mothers'
      PTSS at T2 and at T3. Clinical suggestions are proposed on the basis of our
      empirical findings in order to plan informative, clinical and practical
      interventions for mothers of children under treatment for leukaemia.

PMID- 22640641
TI  - Comparison of linear mixed model analysis and genealogy-based haplotype
      clustering with a Bayesian approach for association mapping in a pedigreed
      population.
AB  - BACKGROUND: Despite many success stories of genome wide association studies
      (GWAS), challenges exist in QTL detection especially in datasets with many levels
      of relatedness. In this study we compared four methods of GWA on a dataset
      simulated for the 15th QTL-MAS workshop. The four methods were 1) Mixed model
      analysis (MMA), 2) Random haplotype model (RHM), 3) Genealogy-based mixed model
      (GENMIX), and 4) Bayesian variable selection (BVS). The data consisted of
      phenotypes of 2000 animals from 20 sire families and were genotyped with 9990
      SNPs on five chromosomes. RESULTS: Out of the eight simulated QTL, these four
      methods MMA, RHM, GENMIX and BVS identified 6, 6, 8 and 7 QTL respectively and 4
      QTL were common across the methods. GENMIX had the highest power to detect QTL
      however it also produced 4 false positives. BVS was the second best method in
      terms of power, detecting all QTL except the one on chromosome 5 with epistatic
      interaction. Two spurious associations were obtained across methods. Though all
      the methods considered the full pedigree in the analyses, it was not sufficient
      to avoid all the spurious associations arising due to family structure.
      CONCLUSIONS: Using several methods with divergent approaches for GWAS can be
      useful in gaining confidence on the QTL identified. In our comparison, GENMIX was
      found to be the best method in terms of power but it needs appropriate correction
      for multiple testing to avoid the false positives. This study shows that the
      issues of multiple testing and the relatedness among study samples need special
      attention in GWAS.

PMID- 22640637
TI  - The effects of perceptual encoding on the magnitude of object working memory
      impairment in schizophrenia.
AB  - Deficits in the visual working memory (WM) system have been consistently reported
      in schizophrenia patients, but the relative contribution of initial perceptual
      encoding to these deficits remains unsettled. We assessed the role of visual
      perceptual encoding on performance on an object WM task. Schizophrenia patients
      (N=37) and nonpsychiatric control subjects (N=33) were tested on an object WM
      task involving three delay periods: 200 ms, 3s, and 10s. Schizophrenia patients
      performed significantly less accurately than controls on all three conditions.
      However, after controlling for the effect of perceptual encoding (accuracy on the
      200 ms delay condition) on performance in the two memory load conditions,
      schizophrenia patients demonstrated intact WM in the 3s delay condition, and
      showed a weak trend for decreased accuracy on the 10s delay compared with
      controls. Analysis of individual differences in pattern of performance revealed
      that a distinct subgroup of poor encoder patients had a significantly greater
      reduction in accuracy at 3s than the other patient subgroups and controls. In
      contrast, among schizophrenia patients who performed poorly on the 10s delay,
      accuracy was equivalently reduced independent of encoding ability. WM deficits in
      controls were independent of encoding ability at both delay intervals. These
      results indicate that encoding ability titrates the magnitude of WM impairment in
      schizophrenia patients but not in controls, and that heterogeneity has to be
      taken into account to correctly estimate the effects of perceptual encoding on
      visual object WM deficits in schizophrenia.

PMID- 22640642
TI  - Molecular basis of intramolecular electron transfer in proteins during radical
      mediated oxidations: computer simulation studies in model tyrosine-cysteine
      peptides in solution.
AB  - Experimental studies in hemeproteins and model Tyr/Cys-containing peptides
      exposed to oxidizing and nitrating species suggest that intramolecular electron
      transfer (IET) between tyrosyl radicals (Tyr-O(.)) and Cys residues controls
      oxidative modification yields. The molecular basis of this IET process is not
      sufficiently understood with structural atomic detail. Herein, we analyzed using
      molecular dynamics and quantum mechanics-based computational calculations,
      mechanistic possibilities for the radical transfer reaction in Tyr/Cys-containing
      peptides in solution and correlated them with existing experimental data. Our
      results support that Tyr-O(.) to Cys radical transfer is mediated by an acid/base
      equilibrium that involves deprotonation of Cys to form the thiolate, followed by
      a likely rate-limiting transfer process to yield cysteinyl radical and a Tyr
      phenolate; proton uptake by Tyr completes the reaction. Both, the pKa values of
      the Tyr phenol and Cys thiol groups and the energetic and kinetics of the
      reversible IET are revealed as key physico-chemical factors. The proposed
      mechanism constitutes a case of sequential, acid/base equilibrium-dependent and
      solvent-mediated, proton-coupled electron transfer and explains the dependency of
      oxidative yields in Tyr/Cys peptides as a function of the number of alanine
      spacers. These findings contribute to explain oxidative modifications in proteins
      that contain sequence and/or spatially close Tyr-Cys residues.

PMID- 22640643
TI  - Breast reconstruction in bilateral prophylactic mastectomy patients: factors that
      influence decision making.
AB  - BACKGROUND: Utilization of bilateral prophylactic mastectomy (BPM) and
      reconstruction has increased secondary to numerous medical advances. The purpose
      of this study was to examine decision making in women electing this therapy to
      further understand what influences and drives this decision. METHODS: The authors
      conducted a survey study, enrolling patients who elected BPM and reconstruction.
      Participants were mailed structured questionnaires utilizing validated and study
      specific tools addressing: demographics, treatment decisions, autonomy, decision
      making and information seeking preferences, and breast cancer treatment
      knowledge. Analysis was performed overall and by reconstruction. RESULTS: 40
      patients responded (20 autologous, 19 implant and 1 combination, 66% response
      rate). The cohort was well educated and wealthy. Reconstructive options played a
      large role in the consideration of BPM. Patients were influenced by their
      physicians and less so by non-traditional means (media, internet, etc).
      Autologous reconstructions had a stronger desire to utilize their own tissue (p <
      0.001) and were less concerned with the amount of surgery (0.02) and resulting
      scars (p = 0.01). Implant reconstructions more often stated that they did not
      have enough tissue for autologous reconstruction (p < 0.001) and did have a lower
      BMI, 24.2 vs. 27.5 (p = 0.03). Additionally, they were more influenced by non
      traditional means (p < 0.001) and by other patients (p = 0.02). CONCLUSIONS:
      Multiple factors influence decision making in BPM and reconstruction, with the
      ultimate choice in reconstruction involving tissue availability, appearance of
      implant reconstructions, total amount of surgery required, and extent of visible
      scars. Patients were strongly influenced by their physicians, and less so by non
      traditional means.

PMID- 22640644
TI  - Development of a patient-specific simulator for laparoscopic renal surgery.
AB  - OBJECTIVES: To describe the development of a patient-specific simulator for
      laparoscopic renal surgery. METHODS: Image data of each patient scheduled to
      undergo laparoscopic renal surgery are captured by the simulator, enabling each
      patient's organs to be reproduced. The surgeon can carry out a preoperative
      "rehearsal" of the operation by using a simulator based on patient-specific data.
      RESULTS: The simulator is programmed to be adapted to both laparoscopic and
      retroperitoneoscopic surgery. The scope and the trocars can be located anywhere
      on the skin, and visualized on the monitor of the simulator. Dissection of the
      renal hilum can be simulated based in the anatomy of each patient. The haptic
      device of the simulator provides interactive resistance between the organs and
      surgical tools during the simulation. CONCLUSIONS: This patient-specific
      simulator has been developed with the purpose of providing surgeons with a
      practical training tool for laparoscopic renal surgery. Using specific data for
      each patient, the simulator enables surgeons to carry out a "rehearsal"
      operation.

PMID- 22640646
TI  - Perspectives: modelling the vasculitis and granulomatous tissue destruction of
      granulomatosis with polyangiitis (GPA).

PMID- 22640645
TI  - Regulation of triglyceride metabolism by glucocorticoid receptor.
AB  - Glucocorticoids are steroid hormones that play critical and complex roles in the
      regulation of triglyceride (TG) homeostasis. Depending on physiological states,
      glucocorticoids can modulate both TG synthesis and hydrolysis. More intriguingly,
      glucocorticoids can concurrently affect these two processes in adipocytes. The
      metabolic effects of glucocorticoids are conferred by intracellular
      glucocorticoid receptors (GR). GR is a transcription factor that, upon binding to
      glucocorticoids, regulates the transcriptional rate of specific genes. These GR
      primary target genes further initiate the physiological and pathological
      responses of glucocorticoids. In this article, we overview glucocorticoid
      regulated genes, especially those potential GR primary target genes, involved in
      glucocorticoid-regulated TG metabolism. We also discuss transcriptional
      regulators that could act with GR to participate in these processes. This
      knowledge is not only important for the fundamental understanding of steroid
      hormone actions, but also are essential for future therapeutic interventions
      against metabolic diseases associated with aberrant glucocorticoid signaling,
      such as insulin resistance, dyslipidemia, central obesity and hepatic steatosis.

PMID- 22640647
TI  - Treatment of Churg-Strauss syndrome: options for the future.

PMID- 22640648
TI  - Intra- and inter-rater reliability of endonasal activity estimation in
      granulomatosis with polyangiitis (Wegener's).
AB  - OBJECTIVES: Granulomatosis with polyangiitis (GPA) frequently starts with an
      affection of the nasal and paranasal mucosa. Localised GPA of the nasal mucosa or
      persistent disease activity ('grumbling disease') is often encountered even under
      immunosuppressive therapy. Necessity for reconstructive surgery is common and
      careful scheduling to prevent failure and minimise revision rates is crucial.
      Therefore, reliable estimation of GPA activity in the upper airways using a score
      is mandatory for diagnosis, follow-up and scheduling reconstructive surgery.
      METHODS: Fifty endoscopic, endonasal images of 45 patients with GPA were used.
      Twelve (4 German, 8 Mexican) experienced (n=7) and inexperienced (n=5) physicians
      assessed GPA-activity at two times (T1/T2) in dichotomy and in a grading approach
      (none, mild, moderate and high activity) using the novel ENT Activity Score
      (ENTAS). All documents were written in English. RESULTS: Estimation of activity
      in dichotomy (none vs. mild/moderate/high): Cohen's Kappa (kappa) for intra-rater
      reliability T1/T2 in inexperienced and experienced physicians was kappa=0.58
      (agreement 85%) and kappa=0.72 (agreement 91%). The inter-rater reliability
      (Fleiss's kappa) T1/T2 for inexperienced and experienced physicians was
      kappa=0.62/kappa=0.59 and kappa=0.50/kappa=0.58 respectively. Estimation of
      activity in grading approach (none, mild, moderate, high): for inexperienced
      physicians the intra-rater reliability T1/T2 was kappa=0.67 (agreement 56%) and
      the inter-rater reliability at T1/T2 was kappa=0.29 (intraclass correlation
      coefficient, ICC=0.69) and kappa=0.27 (ICC=0.59). For experienced physicians the
      intra-rater reliability T1/T2 was kappa=0.80 (agreement 67%) and the inter-rater
      reliability at T1 and T2 was kappa=0.41 (ICC=0.77) and kappa=0.39 (ICC=0.75)
      respectively. CONCLUSIONS: Intra-rater reliability is high in decision in
      dichotomy and even in grading activity. There is no difference for experienced or
      inexperienced physicians. Inter-rater reliability is high in dichotomy, but low
      for activity grading. Thus, the ENTAS provides a reliable instrument for
      assessing, documenting and following GPA-related disease activity in the upper
      respiratory tract. The relationship of activity and following damage needs to be
      investigated in further studies.

PMID- 22640649
TI  - Expression of NKG2D and CD107 in CD8(+) effector memory lymphocytes in Churg
      Strauss syndrome.
AB  - OBJECTIVES: Churg-Strauss syndrome (CSS) is a necrotising vasculitis of small
      vessels in which oligoclonally expanded TCR Vbeta CD8+ effector memory T cells
      populations (TEM) may be involved in vasculitic damage. The aim of this study was
      to assess the functional role of CD8+ T cells in CSS patients by flow cytometry
      analysis of membrane expression of cytotoxic markers NKG2D and CD107a. METHODS:
      Immunostaining of peripheral T cells and effector memory lymphocytes (TEM) from
      CSS patients and controls was performed by gating CD28 and CD45RA in the
      CD8+NKG2D+ and CD4+NKG2D+ populations. CD107a expression was evaluated in both
      whole CD8+ and CD4+ and the TEM cells by gating CD62 and CD45RA following
      polyclonal stimulation. RESULTS: NKG2D expression was shifted toward the CD8+CD28
      fraction of T cells in CSS patients compared to healthy controls (56.1+/-25.8%
      versus 17.2+/-7.3%, respectively, p=0.002). CD8+Vbeta+ expanded T cells showed a
      significantly increased expression of NKG2D compared to the whole CD8+ T cell
      population (91.4+/-1.9% versus 79.7+/-3.8%, respectively, p=0.015). Moreover the
      CD8+ population from CSS upregulates CD107a on its surface upon polyclonal
      stimulation in a significantly higher proportion than healthy subjects (26.2+/
      10.8% versus 8.2+/-2.9%, p=0.0031) and the majority CD8+ CD107+ cells from CSS
      patients showed a TEM phenotype compared to controls (64.8+/-4.9% vs. 19.8+/-2.9,
      respectively, p<0.001). CONCLUSIONS: In CSS, CD8+ TEM lymphocytes show markers of
      cytotoxic activity, which suggests a role for these cells in vasculitic damage.

PMID- 22640650
TI  - Treatment of refractory giant cell arteritis with cyclophosphamide:a
      retrospective analysis of 35 patients from three centres.
AB  - Patients with giant cell arteritis (GCA) refractory to standard immunosuppressive
      therapy may constitute a significant clinical problem with a high risk of
      glucocorticoid-related adverse effects. OBJECTIVES: To evaluate efficacy and
      safety of cyclophosphamide for remission induction in GCA patients with
      persistent disease activity despite standard immunosuppressive treatment.
      METHODS: Thirty-five individuals from 3 tertiary rheumatological centres treated
      for persistently active GCA unresponsive to treatment with glucocorticoids plus
      at least either methotrexate or azathioprine for a minimum of 3 months and unable
      to reduce daily glucocorticoid dose to <10 mg prednisolone equivalent. We
      recorded signs of disease activity (clinical, laboratory, imaging); course of
      glucocorticoid doses during cyclophosphamide treatment and follow-up; relapse
      rate; treatment-related adverse events; and survival. Since all patients had been
      refractory to standard therapy, a matched control group could not be defined.
      RESULTS: Data from 31 patients completing cyclophosphamide treatment were
      available for analysis. Twenty-eight patients (90.3%) responded with improved
      disease activity and sustained reduction of daily prednisolone intake to <10 mg
      (mean reduction -13.1 mg or -51.6%, p<0.001). Twelve months later, doses <7.5 or
      <5 mg were achieved in 89.3% and 67.7% of these patients on maintenance
      immunosuppressive treatment, respectively. Relapses occurred in 12 patients after
      a median of 20.5 months. Survival over 5 years was similar to expected rates of
      the general population. Adverse events comprised transient leucopenia, infections
      and 1 case of haemorrhagic cystitis. CONCLUSIONS: Cyclophosphamide can be
      considered a therapeutic option with an acceptable safety profile for remission
      induction in GCA refractory to standard immunosuppressive treatment.

PMID- 22640651
TI  - Alveolar haemorrhage in ANCA-associated vasculitides: 80 patients' features and
      prognostic factors.
AB  - OBJECTIVES: Alveolar haemorrhage (AH) can be a mild or life-threatening
      manifestation of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides
      (AAV), but its prognostic impact and specific characteristics remain
      controversial. Our objective was to determine the prognostic value of AH in this
      context. METHODS: AH episodes that occurred, between 1991 and 2010, in AAV
      patients entered in the FVSG database were retrospectively analysed. Data on AH
      characteristics and outcome measures were collected on a specific form. RESULTS:
      Among the 80 cases analysed, AAV were 61.25% granulomatosis with polyangiitis
      (GPA) (Wegener), 26.25% microscopic polyangiitis (MPA), 10% Churg-Strauss
      syndrome and 2 (2.5%) unclassified. Mild or severe haemoptysis alone, or together
      with other clinical symptoms was present in 77 (96.2%) patients before AAV
      diagnosis. Among 10 (12.5%) patients requiring mechanical ventilation, 4 had
      prior minor haemoptysis before abundant AH. Sixty-one (76.3%) patients had
      concomitant active rapid crescentic glomerulonephritis causing renal
      insufficiency (pulmo-renal syndrome): 37/49 GPA (Wegener) (75.5% of all GPA
      (Wegener)), 19/21 MPA (90.4% of all MPA), 3/8 had CSS and 2/2 had unclassified
      vasculitis. The mean AH-to-treatment-onset interval was 5.9 days. Mean follow-up
      was 7.3 years. Forty-seven (58.8%) patients relapsed: 23 with AH and with (13) or
      without (10) other organ involvement, 24 with non-AH manifestation(s). Three
      patients underwent kidney transplantation. Sixteen (20%, 8 GPA (Wegener) and 8
      MPA) patients died. No death resulted directly from the initial AH; 14 (87.5%)
      patients with pulmo-renal syndrome died. CONCLUSIONS: As previously demonstrated
      by the Five-Factor Score, AH alone is not predictive of poor prognosis, unlike
      kidney involvement, which dictates a poor outcome.

PMID- 22640652
TI  - Immunogenicity and safety of seasonal and 2009 pandemic A/H1N1 influenza vaccines
      for patients with autoimmune diseases:  a prospective, monocentre trial on 199
      patients.
AB  - OBJECTIVES: The 2009 pandemic A/H1N1 influenza outbreak represented a theoretical
      risk for patients with autoimmune diseases (AID), especially those
      immunosuppressed. This study was undertaken to evaluate immunogenicity and
      tolerance of seasonal (SFV) and A/H1N1 flu vaccines (HFV) in AID patients.
      METHODS: This prospective, open, monocentre, vaccine phase-III study on 199
      patients with AID (systemic necrotising vasculitides, progressive systemic
      sclerosis, systemic lupus erythematosus, Sjogren's syndrome and others), treated
      or not with immunosuppressants, was conducted from September 2009 to June 2010,
      to evaluate SFV and HFV efficacy and safety. Subjects received SFV (1 dose,
      Mutagrip(r)) and/or non-adjuvant HFV (Panenza(r), 2 doses at a 3-week interval).
      The primary judgment criterion was the seroprotection rate. Secondary outcome
      measures were seroconversion rates, vaccine tolerance, and numbers of flu
      syndromes, and AID flares and relapses throughout the 6 month observation period.
      RESULTS: After SFV inoculation, 1% of the patients became febrile, 18% developed
      local reactions, 80% were seroprotected and 38% seroconverted. After HFV
      immunisation, 4% of the patients developed a fever, 23% had local reactions, 65%
      were seroprotected and 83% seroconverted. Twelve patients developed 15 flu
      syndromes (3 patients developed 2 syndromes each); 2 of these episodes were
      temporally consistent with vaccination; 1 patient died of septic shock unrelated
      to vaccination. Nineteen mild AID flares occurred during follow-up, only 6 being
      temporally consistent with HFV and SFV. CONCLUSIONS: Our findings demonstrated
      the safety and efficacy of SFV and HFV in AID patients.

PMID- 22640653
TI  - Thiabendazole-induced acute liver failure requiring transplantation and
      subsequent diagnosis of polyarteritis nodosa.
AB  - Polyarteritis nodosa (PAN), a systemic necrotising vasculitis that affects medium
      and small-sized arteries, has visceral involvement in 40-60% of the patients.
      According to the Five-Factor Score (FFS), it is associated with poor outcome. We
      describe a patient who underwent orthotopic liver transplantation (OLT) for
      severe ductopenia induced by thiabendazole that was empirically prescribed for
      chronic hypereosinophilia. Eleven years later, despite immunosuppressive
      treatment to prevent graft rejection, he developed mononeuritis multiplex; PAN
      was diagnosed. He also had severe recurrent ischaemic cholangitides because of
      post-OLT hepatic artery ligation to treat a postoperative severe haematemesis.
      His outcome was favourable after second OLT, under steroids, cyclophosphamide
      pulses and tacrolimus. In retrospect, his initial symptoms and hypereosinophilia
      were probably attributable to PAN.

PMID- 22640654
TI  - Polymyalgia rheumatica as presenting manifestation of vasculitis involving the
      lower extremities in a patient with ulcerative colitis.
AB  - Extraintestinal features may be observed in patients with ulcerative colitis
      (UC). We describe a 69-year-old woman who was initially diagnosed as having
      polymyalgia rheumatica (PMR). Prednisone was progressively tapered to complete
      discontinuation a year and a half after PMR diagnosis. However, at that time, she
      started to complain of asthenia, abdominal cramping and pain on the left side,
      weight loss and bloody diarrhoea. A colonoscopy confirmed a diagnosis of left
      sided UC. She experienced several flares of the disease that required admission
      and treatment with high-dose corticosteroids and azathioprine. Colectomy was
      performed as the disease became refractory to these therapies. Four months after
      surgery, when the patient was not receiving any corticosteroid therapy, she
      started to feel dull and achy pain in the thighs along with claudication of the
      lower limbs. An 18F-fluorodeoxyglucosepositron emission tomography with CT (FDG
      PET/CT) disclosed an inflammatory process with mild-moderate diffuse increased
      metabolism in the thoracic aorta and markedly increased FDG uptake in the in the
      femoral and posterior tibial arteries on both sides. Treatment with the anti-TNF
      alpha monoclonal antibody-adalimumab (40 mg every 2 weeks subcutaneously) along
      with prednisone (initial dose 15 mg/day) yielded rapid improvement of symptoms.
      Also, a new FDG PET/CT performed 4 months later disclosed marked decrease of FDG
      uptake in the involved arteries.This report emphasises the importance of
      suspecting the presence of large- and medium-vessel vasculitis in a patient with
      UC presenting with musculoskeletal features. It also highlights the beneficial
      effect of TNF-antagonists in vasculitis associated to UC.

PMID- 22640655
TI  - Does glucocorticosteroid-resistant large-vessel vasculitis (giant cell arteritis
      and Takayasu arteritis) exist and how can remission be achieved? A critical
      review of the literature.
AB  - OBJECTIVES: The mainstay in the treatment of the large-vessel vasculitides giant
      cell arteritis (GCA) and Takayasu arteritis (TA) are glucocorticosteroids (GC)
      for induction of remission as well as for its maintenance in low doses for 1 to 2
      years. However, clinical practice includes GC-resistant cases without sufficient
      response to standard GC for induction of remission and GC-dependent cases where a
      dose reduction of GC without relapse is impossible after successful induction of
      remission. The aim of this study was to evaluate the data on treatment options in
      these situations. METHODS: A literature search in PubMed matching the terms TA
      and GCA as well as temporal arteritis with all possible immunosuppressive and
      biological agents as well as with the terms 'treatment, therapy and management'
      was performed. RESULTS: Sixty-four publications were found. Five case series
      described large cohorts of patients with GCA (n=2) or TA (n=3) showing that 40.8%
      to 48% of GCA patients and 46% to 84% of TA patients require additional
      immunosuppressive agents to achieve remission and taper GC. Most were on biologic
      agents (mainly infliximab, 24 publications/123 patients), followed by
      methotrexate (MTX) (14/113), cyclophosphamide (CYC) (9/27), azathioprine (AZA)
      (8/51), cyclosporine A (CSA) (6/47), mycophenolate mofetil (MMF) (3/32),
      leflunomide (LEF) (2/2), chlorambucil (1/1) and antimalarials (1/36). There were
      also 2 case reports on autologous stem cell transplantation. The distribution of
      the two entities TA and GCA was as follows: MTX: 98% GCA, 2% TA; IFX: 26.8% GCA,
      73.2% TA; CYC: 70.4% GCA, 29.6% TA; AZA: 100% GCA; LEF: 100% TA; MMF: 100% TA;
      antimalarials: 100% GCA, autologous stem cell transplantation: 100% TA. A
      distinction between GC-resistant and GC-dependent cases could not be made from
      the data available. However, 50 (79%) of the publications described GC-resistant
      cases. Whereas almost all case reports and retrospective case series (with the
      exception of CSA) revealed steroid-sparing effects, the 3 prospective randomised
      trials and 2 open prospective controlled trials on MTX gave conflicting results.
      However, a recent meta-analysis which recalculated the original data resulted in
      superiority of MTX after 24 months, there were less relapses and lower GC doses
      in the MTX group. The prospective controlled IFX trial where IFX was randomised
      against placebo after GC-induced remission of GCA did not show advantages for IFX
      over GC alone for maintenance of remission. The prospective controlled ETA trial,
      which comprised 17 GCA patients, showed small, non-significant advantages but was
      too small to draw definite conclusions. CONCLUSIONS: Although GCA is the
      commonest systemic vasculitis, prospective randomised trials on steroid sparing
      agents are rare and mostly included only small patient numbers. Inclusion and
      response criteria were heterogeneous, and observation periods and follow-up were
      often short. Criteria for GC-resistance or GC-dependence and for disease
      remission have not been uniformly defined. There is still an urgent need for
      prospective randomised trials with larger patient groups, longer follow-up and
      well defined inclusion criteria and criteria for response and relapse, using
      standardised disease activity scoring systems, in order to be able to give
      evidence-based recommendations for patients not responding to GC alone in the
      future.

PMID- 22640656
TI  - Large- and small-vessel vasculitis: a critical digest of the 2010-2011
      literature.
AB  - The last two years have been marked by significant achievement in the
      identification of the basic mechanisms of systemic vasculitis and in the
      translation of these mechanisms into targeted therapies. More specifically, new
      insights into the environmental, cellular, and genetic factors involved in the
      pathogenesis of systemic vasculitis have been provided. Consequently, several
      studies focused on the development of novel strategies to achieve and maintain
      clinical remission in small- and large-vessel vascultis, including relevant large
      multicentre trials, have been promoted. The highlights of these studies, their
      potential clinical implications and the unmet needs, which are still to be
      addressed, are summarised in this review.

PMID- 22640657
TI  - Recommendations of the Italian Society of Rheumatology for the treatment of the
      primary large-vessel vasculitis with biological agents.
AB  - OBJECTIVES: To provide recommendations on behalf of the Italian Society for
      Rheumatology for the off-label use of biologic agents in the treatment of large
      vessel vasculitis. METHODS: A panel of experts performed a literature search and
      selected the evidence relevant to the topic. The following five large-vessel
      vasculitides were considered: giant cell arteritis, Takayasu arteritis, primary
      angiitis of the central nervous system, Cogan's syndrome, and Adamantiades
      Behcet's disease. RESULTS: A consensus was achieved regarding the indication of
      biologic agents for the treatment of large-vessel vasculitis. Levels of evidence
      were assigned to the papers retrieved, and the strength of the recommendations
      was graded according to the levels of evidence. CONCLUSIONS: These
      recommendations may be used for guidance in deciding which patients with large
      vessel vasculitis should receive biologic therapy. Further updates of these
      recommendations may be published on the basis of the results of new clinical
      studies and of data from post-marketing surveillance.

PMID- 22640658
TI  - Performance of Birmingham Vasculitis Activity Score and disease extent index in
      childhood vasculitides.
AB  - OBJECTIVES: To evaluate the performance of the Birmingham Vasculitis Activity
      Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease
      activity in 4 primary childhood (c-) systemic vasculitides. METHODS: Patients
      fulfilling the EULAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria
      for Henoch-Schonlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c
      Wegener's granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease
      duration at the time of diagnosis <=3 months were extracted from the PRINTO
      database. The performance of the BVAS and DEI were examined by assessing
      convergent validity, the pattern of disease involvement, and responsiveness. We
      also evaluated alternative unweighted scoring methods for both tools. RESULTS:
      The analysis set included 796 patients with 669 HSP, 80 c-PAN, 25 c-WG and 22 c
      TA. The median age at diagnosis was 6.9 years (6.6-12) and median delay in making
      the diagnosis from the onset of signs/symptoms was 0.01 (0.003-0.027) years. A
      strong correlation was found between the BVAS and DEI (rs=0.78) while correlation
      with the physician global assessment was moderate (rs=0.48) with BVAS and poor
      with DEI (rs=0.25). Both the BVAS and DEI sub-scores and total scores were able
      to descrive the disease involvement in the 4 childhood vasculitides.
      Responsiveness was large (>1.5) for both tools. The performance characteristics
      of the BVAS and DEI with the unweighted methods were comparable. CONCLUSIONS:
      This study demonstrates that both the BVAS and DEI are valid tools for the
      assessment of the level of disease activity in a large cohort of childhood acute
      and chronic vasculitides.

PMID- 22640659
TI  - Increased frequency of IL-7 and IL-15 receptor alpha chain (CD127, CD215) co
      expressing CD4(+) T cells in granulomatosis with polyangiitis (Wegener's).

PMID- 22640660
TI  - Co-contraction patterns of trans-tibial amputee ankle and knee musculature during
      gait.
AB  - BACKGROUND: Myoelectric control of upper extremity powered prostheses has been
      used clinically for many years, however this approach has not been fully
      developed for lower extremity prosthetic devices. With the advent of powered
      lower extremity prosthetic components, the potential role of myoelectric control
      systems is of increasing importance. An understanding of muscle activation
      patterns and their relationship to functional ambulation is a vital step in the
      future development of myoelectric control. Unusual knee muscle co-contractions
      have been reported in both limbs of trans-tibial amputees. It is currently
      unknown what differences exist in co-contraction between trans-tibial amputees
      and controls. This study compares the activation and co-contraction patterns of
      the ankle and knee musculature of trans-tibial amputees (intact and residual
      limbs), and able-bodied control subjects during three speeds of gait. It was
      hypothesized that residual limbs would have greater ankle muscle co-contraction
      than intact and able-bodied control limbs and that knee muscle co-contraction
      would be different among all limbs. Lastly it was hypothesized that the extent of
      muscle co-contraction would increase with walking speed. METHODS: Nine unilateral
      traumatic trans-tibial amputees and five matched controls participated. Surface
      electromyography recorded activation from the Tibialis Anterior, Medial
      Gastrocnemius, Vastus Lateralis and Biceps Femoris of the residual, intact and
      control limbs. A series of filters were applied to the signal to obtain a linear
      envelope of the activation patterns. A co-contraction area (ratio of the
      integrated agonist and antagonist activity) was calculated during specific phases
      of gait. RESULTS: Co-contraction of the ankle muscles was greater in the residual
      limb than in the intact and control limbs during all phases of gait. Knee muscle
      co-contraction was greater in the residual limb than in the control limb during
      all phases of gait. CONCLUSION: Co-contractions may represent a limb stiffening
      strategy to enhance stability during phases of initial foot-contact and single
      limb support. These strategies may be functionally necessary for amputee gait;
      however, the presence of co-contractions could confound future development of
      myoelectric controls and should thus be accounted for.

PMID- 22640661
TI  - Numerical analysis of the radial force produced by the Medtronic-CoreValve and
      Edwards-SAPIEN after transcatheter aortic valve implantation (TAVI).
AB  - A better understanding of the mechanisms producing the radial force in
      transcatheter heart valves is essential in order to reduce the reported cases of
      migration and atrio-ventricular block and improve the effectiveness of the
      treatment. This paper presents a numerical study of the different mechanisms
      responsible for the radial force exerted on the aortic annulus by self-expanding
      and balloon-expandable prostheses. The behavior of the Medtronic CoreValve (self
      expanding) and the Edwards SAPIEN (balloon-expandable) devices, both of size 26,
      has been simulated and compared. The results indicate that, for both prostheses,
      the radial force may vary considerably within the recommended functional range
      for the valve implantation and is substantially higher at the smallest annular
      sizes. In particular, in the case of the self-expanding valve the radial force is
      essentially dependent on the diameter of the left ventricular outflow tract,
      while for the balloon-expandable valve the radial force produced is influenced by
      both the geometry and stiffness of the host tissue. The outcomes of this study
      provide a better insight into the phenomenon and useful information that could
      support the development of improved solutions.

PMID- 22640662
TI  - Concurrent radiochemotherapy in locally-regionally advanced oropharyngeal
      squamous cell carcinoma: analysis of treatment results and prognostic factors.
AB  - BACKGROUND: Concurrent radiochemotherapy is a recommended treatment option for
      patients with locally advanced squamous cell head and neck carcinomas with recent
      data showing the most significant absolute overall and event-free survival
      benefit achieved in patients with oropharyngeal tumours. The aim of this study
      was to analyse the results of three-dimensional conformal radiotherapy given with
      concomitant weekly cisplatin in patients with advanced oropharyngeal carcinoma
      and to identify prognostic factors influencing outcomes of this patients
      category. METHODS: Sixty-five patients with stage III or IV squamous cell
      carcinoma of the oropharynx who underwent concurrent radiochemotherapy between
      January 2005 and December 2010 were retrospectively analyzed. All patients
      received radiotherapy to 70 Gy/35 fractions/2 Gy per fraction/5 fractions per
      week. Concurrent chemotherapy consisted of weekly cisplatin (30 mg/m(2)) started
      at the first day of radiotherapy. RESULTS: Median age was 57 years (range, 36 to
      69 years) and 59 (90.8%) patients were male. Complete composite response was
      achieved in 47 patients (72.3%). Local and/or regional recurrence was the most
      frequent treatment failure present in 19 out of 25 patients (76.0%). At a median
      follow-up of 14 months (range, 5 to 72 months), 2-year local relapse-free,
      regional relapse-free, locoregional relapse-free, disease-free, and overall
      survival rates were 48.8%, 57.8%, 41.7%, 33.2% and 49.7%, respectively.On
      multivariate analysis the only significant factor for inferior regional relapse
      free survival was the advanced N stage (p = 0.048). Higher overall stage was
      independent prognostic factor for poorer local relapse-free survival,
      locoregional relapse-free survival and disease-free survival (p = 0.022, p =
      0.003 and p = 0.003, respectively). Pre-treatment haemoglobin concentration was
      an independent prognostic factor for local relapse-free survival, regional
      relapse-free survival, locoregional relapse-free survival, disease-free survival,
      and overall survival (p = 0.002, p = 0.021, p = 0.001, p = 0.002 and p = 0.002,
      respectively). CONCLUSIONS: Poor treatments results of this study suggested that
      introduction of intensity-modulated radiotherapy, use of induction chemotherapy
      followed by concurrent radiochemotherapy, accelerated radiotherapy regimens, and
      molecular targeted therapies could positively influence treatment outcomes. The
      incorporation of reversal of anaemia should be also expected to provide further
      improvement in locoregional control and survival in patients with advanced
      squamous cell carcinoma of the oropharynx.

PMID- 22640663
TI  - Structural correlates of facial emotion recognition deficits in Parkinson's
      disease patients.
AB  - The ability to recognize facial emotion expressions, especially negative ones, is
      described to be impaired in Parkinson's disease (PD) patients. Previous
      neuroimaging work evaluating the neural substrate of facial emotion recognition
      (FER) in healthy and pathological subjects has mostly focused on functional
      changes. This study was designed to evaluate gray matter (GM) and white matter
      (WM) correlates of FER in a large sample of PD. Thirty-nine PD patients and 23
      healthy controls (HC) were tested with the Ekman 60 test for FER and with
      magnetic resonance imaging. Effects of associated depressive symptoms were taken
      into account. In accordance with previous studies, PD patients performed
      significantly worse in recognizing sadness, anger and disgust. In PD patients,
      voxel-based morphometry analysis revealed areas of positive correlation between
      individual emotion recognition and GM volume: in the right orbitofrontal cortex,
      amygdala and postcentral gyrus and sadness identification; in the right occipital
      fusiform gyrus, ventral striatum and subgenual cortex and anger identification,
      and in the anterior cingulate cortex (ACC) and disgust identification. WM
      analysis through diffusion tensor imaging revealed significant positive
      correlations between fractional anisotropy levels in the frontal portion of the
      right inferior fronto-occipital fasciculus and the performance in the
      identification of sadness. These findings shed light on the structural neural
      bases of the deficits presented by PD patients in this skill.

PMID- 22640664
TI  - Where are the great role models?

PMID- 22640666
TI  - Space changes after premature loss of deciduous molars.

PMID- 22640667
TI  - When to say "I'm sorry".

PMID- 22640669
TI  - What's in a title? An assessment of whether randomized controlled trial in a
      title means that it is one.
AB  - INTRODUCTION: In this study, we aimed to investigate whether studies published in
      orthodontic journals and titled as randomized clinical trials are truly
      randomized clinical trials. A second objective was to explore the association of
      journal type and other publication characteristics on correct classification.
      METHODS: American Journal of Orthodontics and Dentofacial Orthopedics, European
      Journal of Orthodontics, Angle Orthodontist, Journal of Orthodontics,
      Orthodontics and Craniofacial Research, World Journal of Orthodontics, Australian
      Orthodontic Journal, and Journal of Orofacial Orthopedics were hand searched for
      clinical trials labeled in the title as randomized from 1979 to July 2011. The
      data were analyzed by using descriptive statistics, and univariable and
      multivariable examinations of statistical associations via ordinal logistic
      regression modeling (proportional odds model). RESULTS: One hundred twelve trials
      were identified. Of the included trials, 33 (29.5%) were randomized clinical
      trials, 52 (46.4%) had an unclear status, and 27 (24.1%) were not randomized
      clinical trials. In the multivariable analysis among the included journal types,
      year of publication, number of authors, multicenter trial, and involvement of
      statistician were significant predictors of correctly classifying a study as a
      randomized clinical trial vs unclear and not a randomized clinical trial.
      CONCLUSIONS: From 112 clinical trials in the orthodontic literature labeled as
      randomized clinical trials, only 29.5% were identified as randomized clinical
      trials based on clear descriptions of appropriate random number generation and
      allocation concealment. The type of journal, involvement of a statistician,
      multicenter trials, greater numbers of authors, and publication year were
      associated with correct clinical trial classification. This study indicates the
      need of clear and accurate reporting of clinical trials and the need for
      educating investigators on randomized clinical trial methodology.

PMID- 22640670
TI  - Surface analysis of study models generated from OrthoCAD and cone-beam computed
      tomography imaging.
AB  - INTRODUCTION: The purpose of this research was to determine the accuracy of
      digital models generated by cone-beam computed tomography and compare it with
      that of OrthoCAD models (Cadent, Carlstadt, NJ) for orthodontic diagnosis and
      treatment planning by using surface area analysis. MATERIALS: Two sets of
      maxillary and mandibular digital models of 30 subjects were obtained. The models
      were made from impressions scanned with OrthoCAD and by conversion of related
      cone-beam computed tomography files. Each patient's matched pairs of maxillary
      and mandibular models were superimposed by using a software program and a best
      fit algorithm; surface-to-surface analysis was then performed. The average linear
      differences between the 2 files at all points on the surfaces were measured, and
      tolerance levels of 0.25, 0.5, 0.75, 1.0, 1.25, and 1.5 mm were set to determine
      the surface correlation amounts between the 2 files. Additionally, 6 linear
      measurements from predetermined landmarks were also measured and analyzed.
      RESULTS: The average maxillary model linear difference was 0.28 to 0.60 mm,
      whereas the average mandibular model linear difference ranged between 0.34 and
      0.61 mm. Greater than a 90% surface correlation was obtained on average at 1.00
      mm in the maxillary models and at 1.25 mm in the mandibular models. The mean
      differences obtained from the linear measurements of the maxillary and mandibular
      models were 0.071 and 0.018 mm, respectively. CONCLUSIONS: Surface-to-surface
      analysis of OrthoCAD and digital models generated by cone-beam computed
      tomography pointed to a fair overlap between the protocols. The accuracy of
      digital models generated by cone-beam computed tomography is adequate for initial
      diagnosis and treatment planning in orthodontics.

PMID- 22640671
TI  - Prospective longitudinal evaluation of the relationship between changes in
      mandibular length and blood-spot IGF-1 measurements.
AB  - INTRODUCTION: The purpose of this study was to develop the use of a biologic
      marker, insulin-like growth factor (IGF-1), as an indicator for the timing and
      intensity of mandibular growth. This was done by measuring annual changes in
      mandibular length and studying how they relate to blood-spot IGF-1 measurements
      and cervical stages. METHODS: Twenty-five patients (12 female, 13 male) from an
      orthodontic population were longitudinally evaluated for annual IGF-1 level,
      cervical stage, and mandibular length. The patients' follow-up periods ranged
      between 1 and 5 years. A total of 43 annual time intervals were gathered (17
      female, 26 male). Annual mandibular growth was related to changes in blood-spot
      IGF-1 levels over each observation period. RESULTS: When the whole sample was
      pooled into 1 group, we found a statistically significant mild to moderate
      correlation between the percentages of change in mandibular length and in IGF-1
      levels (r = 0.4, P = 0.008). When the sample was divided based on whether the IGF
      1 levels were increasing or decreasing at each yearly interval, the group with
      ascending IGF-1 levels had significantly more mandibular growth than did the
      group with descending IGF-1 levels (3.5 and 1.3 mm, respectively; P = 0.026). The
      ascending group had a moderate to high correlation between average IGF-1 levels
      and the amount of mandibular growth for each observation period. Observation
      periods with ascending IGF-1 levels and an average level greater than 250 MUg per
      liter had significantly greater annual mandibular growth than did the rest of the
      patients with ascending IGF-1 levels (5.6 and 2.1 mm, respectively). CONCLUSIONS:
      Blood-spot IGF-1 testing is a promising tool for predicting the timing and the
      intensity of the mandibular growth spurt without the restrictions involved with
      radiographic techniques for assessing skeletal maturity. More research is
      necessary to validate these results in a different population by using more
      advanced imaging tools and a larger sample size. The relationship between IGF-1
      levels and mandibular growth after the pubertal growth spurt is not fully
      understood.

PMID- 22640672
TI  - Effect of surface treatment on cell responses to grades 4 and 5 titanium for
      orthodontic mini-implants.
AB  - INTRODUCTION: Mini-implants are used to improve orthodontic anchorage, but
      optimal composition and surface characteristics have yet to be determined. We
      investigated the behavior of osteoblast-like cells on grade 4 commercially pure
      titanium and grade 5 titanium alloy with different surface treatments for mini
      implants. METHODS: MC3T3 cells were plated on machined, acid-etched, or acid
      etched grade 4 titanium enriched with calcium phosphate, or machined, anodized,
      or anodized and calcium phosphate-enriched grade 5 titanium disks. Surface and
      cell morphologies were assessed by scanning electron microscopy. Cell viability
      was measured by chemiluminescence, cytoskeletal organization was investigated by
      immunofluorescence, and real-time polymerase chain reaction for osteoblast
      specific genes was performed to measure cell differentiation. RESULTS: Flattened
      shapes and strong stress fibers were observed on the machined surfaces; cells on
      the rough surfaces had a spindle shape, with lower cytoskeletal polarization.
      Cell proliferation was highest on smooth grade 4 titanium surfaces, whereas cells
      quickly reached a plateau on rough grade 4 titanium; no difference was observed
      after 72 hours in the grade 5 titanium groups. Calcium phosphate enrichment on
      grade 4 titanium significantly increased the messenger RNA levels for alkaline
      phosphatase and osteocalcin. Osteoblastic markers were higher on the grade 5
      titanium machined surfaces than on the rough surfaces, and comparable with acid
      etched grade 4 titanium. CONCLUSIONS: Although the grade 4 titanium enriched with
      calcium phosphate had the highest level of differentiation in vitro, the grade 5
      titanium machined surfaces supported cell proliferation and matrix synthesis, and
      induced high expression of early differentiation markers. Increased mechanical
      resistance of grade 5 titanium makes it a potential candidate for orthodontic
      mini-implants.

PMID- 22640673
TI  - Clinical efficiency of nonconventional elastomeric ligatures in the canine
      retraction phase of preadjusted edgewise appliance therapy: an in-vivo study.
AB  - INTRODUCTION: Various ligation techniques and materials have been shown to affect
      the frictional resistance and the rate of tooth movement with sliding mechanics
      for space closure. The aim of this study was to evaluate the clinical efficiency
      of nonconventional elastomeric ligatures and conventional elastomeric ligatures
      during the canine retraction phase by comparing the rates of canine retraction.
      METHODS: The 20 patients (12 female, 8 male) in our sample had individual canine
      retraction (in the first premolar extraction space) in each quadrant (2
      maxillary, 2 mandibular) with nonconventional elastomeric ligatures and
      conventional elastomeric ligatures on either side of the arch. The amount of
      canine retraction in each interval of 1 month was determined. The rate of canine
      retraction was calculated and subjected to statistical calculations. RESULTS: The
      rates of canine retraction were higher with the nonconventional elastomeric
      ligatures. However, no statistically significant difference was observed in
      relation to the maxillary arch. Clinically, in most instances, canine retraction
      was completed in the same interval in both groups. CONCLUSIONS: No significant
      difference in the rate of canine retraction was observed between the
      nonconventional elastomeric ligature and conventional elastomeric ligature groups
      in the maxillary arch. Clinically, the nonconventional elastomeric ligature group
      showed no reduction in time required for complete canine retraction in the
      maxillary and mandibular arches.

PMID- 22640674
TI  - Treatment effects of intrusion arches and mini-implant systems in deepbite
      patients.
AB  - INTRODUCTION: The purpose of this study was to compare the skeletal and dental
      effects of 2 intrusion systems involving mini-implants and the Connecticut
      intrusion arch in patients with deepbites. METHODS: The study sample consisted of
      45 adults (26 women, 19 men) with deepbites. They were divided into 3 groups: 2
      treatment groups and 1 untreated control group (15 subjects in each group). The
      Connecticut intrusion arch and the implant groups underwent maxillary incisor
      intrusion with Connecticut intrusion arches and a mini-implant system,
      respectively. During the 7-month study period, no other treatment was performed
      with the exception of maxillary incisor intrusion. RESULTS: The mean amounts of
      genuine intrusion were 2.20 mm (0.31 mm per month) in the Connecticut intrusion
      arch group and 2.47 mm (0.34 mm per month) in the implant group. No statistically
      significant differences were found in the extent of maxillary incisor intrusion
      between the 2 intrusion systems (P >0.05). Both systems led to protrusion and
      intrusion of the maxillary incisors (P <0.05), and protrusion and extrusion of
      the mandibular incisors (P <0.05). In the Connecticut intrusion arch group, the
      maxillary molars were extruded by moving the crown distally and the root
      mesially. The 2 intrusion systems were statistically different in the extent of
      alterations in the axial inclinations of the maxillary molars (P <0.05).
      CONCLUSIONS: Both the Connecticut intrusion arch and the mini-implant intrusion
      systems successfully intruded the 4 maxillary incisors. Although the movement of
      the maxillary molars led to the loss of sagittal and vertical anchorages during
      intrusion of the incisors in the Connecticut intrusion arch group, these
      anchorages were maintained in the implant and control groups.

PMID- 22640675
TI  - Impact of dentofacial deformity and motivation for treatment: a qualitative
      study.
AB  - INTRODUCTION: Satisfaction with the outcome of orthognathic treatment is
      generally high; however, an important minority remains dissatisfied with the
      results. The reasons for this could be inadequate patient understanding and
      preparation, external motivation, and unrealistic expectations. In-depth
      appreciation of these issues can be obtained using qualitative research methods,
      but there is a paucity of qualitative research in this field. METHODS: This was a
      cross-sectional qualitative study of orthognathic patients conducted at a
      teaching hospital. In-depth interviews were conducted with 18 prospective
      orthognathic patients. The data were managed by using the framework approach and
      analyzed by using the critical qualitative theory. RESULTS: Two main themes were
      explored in the interviews: the impact of the dentofacial deformity and the
      motivation for treatment. Both the everyday problems of living with a dentofacial
      deformity and the motivation for seeking treatment could be classified either as
      exclusively practical (including functional and structural), exclusively
      psychological (including psychosocial and esthetic), or a combination. Different
      coping strategies were also described. The sources of motivation ranged between
      purely external to purely internal, with most subjects between these 2 extremes.
      CONCLUSIONS: In this article, we present a classification of the impact of
      dentofacial deformity that is a refinement of the traditional one that includes
      esthetic, functional, and psychosocial factors. The motivating factors, together
      with the triggers for accessing treatment and the source of motivation, are
      generally linked directly or indirectly to the problem and the impact of the
      condition. However, in a few patients, the motivation might not relate to the
      impact of the problem but to a complex array of other factors such as
      personality, upbringing, and relationships. Therefore, clinicians should not make
      assumptions but explore these factors on an individual basis without preconceived
      ideas.

PMID- 22640676
TI  - Influence of orthodontic treatment on adolescents' self-perceptions of esthetics.
AB  - INTRODUCTION: The aim of this prospective evaluation was to assess changes in
      esthetic self-perception of Brazilian adolescents who were receiving fixed
      orthodontic treatment during a 2-year period. METHODS: The treatment group
      consisted of 92 patients, ages 12 to 15 years, treated at the Rio de Janeiro
      State University orthodontic clinic. The control group consisted of 226 untreated
      adolescents; 124 subjects were waiting for treatment at this clinic, and 102
      subjects were attending public school and had never undergone or sought
      treatment. The index of orthodontic treatment need was used to assess
      malocclusion severity, esthetic status (measured by an orthodontist), and
      esthetic self-perception. All subjects were interviewed 3 times during the study:
      at baseline; 1 year after placement of the fixed appliance for the treatment
      group and 1 year after the first interview for the school and waiting groups; and
      2 years after placement of the fixed appliance for the treatment group and 2
      years after the first interview for the school and waiting groups. The index of
      orthodontic treatment need scores were analyzed by using negative binomial
      regression in generalized estimating equations for correlated data. RESULTS:
      During the follow-up period, the treatment group's esthetic self-perception
      scores had a statistically significant decrease (P <0.01), the waiting group's
      scores had an increase (P = 0.08), and the school group's scores were stable (P =
      0.79). At baseline, the treatment group had an esthetic self-perception score of
      96% (risk ratio = 1.96; 95% confidence interval, 1.70-2.26) higher than the
      school group, but at the final interview, the treatment group's score was 20%
      lower (risk ratio = 0.81; 95% confidence interval, 0.68-0.96) than the initial
      score of the school group. Age; sex; the index of decayed, missing, and filled
      teeth; and socioeconomic position did not affect the adolescents' esthetic self
      perceptions at follow up, but malocclusion severity and the group had a
      significant interaction. CONCLUSIONS: Fixed orthodontic treatment in patients 12
      to 15 years of age significantly improved their esthetic self-perceptions.

PMID- 22640677
TI  - How does orthodontic treatment affect young adults' oral health-related quality
      of life?
AB  - INTRODUCTION: Studies in the dental literature do not yet provide conclusive
      evidence for the functional and psychosocial benefits of orthodontic treatment.
      In this cross-sectional study, we aimed to assess the oral health-related quality
      of life of young Brazilian adults, aged 18 to 30 years, who had completed
      orthodontic treatment compared with untreated subjects waiting for treatment.
      METHODS: The subjects were recruited at a state-funded university clinic. The
      sample comprised 100 patients in the retention phase of orthodontic treatment for
      more than 6 months (treated group) and 100 persons who were seeking orthodontic
      treatment and were still on a waiting list (nontreated group). Data were
      collected by using the oral health impact profile, the index of orthodontic
      treatment need (malocclusion severity and esthetic impairment), the Brazilian
      economic classification criteria (socioeconomic status), and the index of
      decayed, missing, and filled teeth (oral health status). Statistical analyses
      were performed by using chi-square and Fisher exact tests and negative binomial
      regression. RESULTS: The mean oral health impact profile scores were 3.1 (SD +/-
      2.99) and 15.1 (SD +/- 8.02) in the treated and nontreated groups, respectively.
      The most frequent impacts in the treated and nontreated groups were "painful
      aching" and "been self-conscious," respectively. Comparisons between the groups
      were controlled for malocclusion severity, clinician-assessed esthetic
      impairment, age, sex, socioeconomic status, and oral health status. Nontreated
      young adults had mean oral health impact profile scores 5.3 times higher than did
      the treated subjects. CONCLUSIONS: Young Brazilian adults who received
      orthodontic treatment had significantly better oral health-related quality of
      life scores in the retention phase, after treatment completion, than did
      nontreated subjects.

PMID- 22640678
TI  - Skeletal and dental outcomes of a new magnetic functional appliance, the Sydney
      Magnoglide, in Class II correction.
AB  - INTRODUCTION: The purpose of this prospective study was to evaluate the
      dentoskeletal effects of a new magnetic functional appliance, the Sydney
      Magnoglide (Macono Orthodontic Lab, Sydney, Australia), after both active
      treatment with the appliance and comprehensive fixed appliance therapy, compared
      with a group of untreated Class II controls. METHODS: Thirty-four consecutively
      treated Class II Division 1 patients treated with the Sydney Magnoglide followed
      by fixed appliances were compared with 30 untreated Class II controls with the
      same initial dentoskeletal Class II features and matched for age and sex. Lateral
      cephalograms were taken before treatment, immediately after functional appliance
      therapy, and after comprehensive fixed appliance therapy. Cephalometric analyses
      included the Pancherz analysis and linear and angular measurements. The
      comparisons were made with Student t tests (P <0.05). There were 3 dropouts, for
      a final sample for statistical analysis of 31 subjects. RESULTS: There was no
      statistically significant difference between the treated and control groups
      before treatment. Treatment with the Sydney Magnoglide and comprehensive fixed
      appliance therapy normalized the overjet and corrected the Class II relationship
      in all treated subjects. The ANB angle showed a reduction of 1.0 degrees , as
      opposed to an increase of 0.3 degrees  in the untreated controls, and was
      associated with a statically significant improvement in the SNB angle (P <0.05).
      There was a significant gain of 2.3 mm in mandibular length in the treated group
      compared with the control group (P <0.01). CONCLUSIONS: The outcomes of this
      prospective study demonstrate that the compliance-free Sydney Magnoglide is an
      effective functional appliance for Class II correction.

PMID- 22640679
TI  - Conservative approach for a patient with extreme delay in maxillary lateral
      incisor development.
AB  - The purpose of this article is to report the orthodontic treatment of a patient
      with extremely delayed development of the maxillary lateral incisors. At 7 years
      of age, the boy's permanent maxillary lateral incisors had not erupted. A
      radiograph showed no tooth germs in place, although well-defined radiolucent
      areas were evident. Removal of the radiolucent areas was contemplated, but it was
      rejected in favor of a conservative approach. At age 13, peg-shaped maxillary
      lateral incisors erupted; they were positioned during orthodontic treatment and
      reshaped with composite restorations, providing good esthetics and function.

PMID- 22640680
TI  - Protraction of mandibular second and third molars into missing first molar spaces
      for a patient with an anterior open bite and anterior spacing.
AB  - In a young woman, aged 18 years 8 months, who had an anterior open bite and
      anterior spacing, the right and left mandibular first molar extraction spaces
      were closed by protraction of the second and third molars without reciprocal
      retraction of the incisors and the premolars. The amounts of protraction for the
      second molars were 12 mm on the right side and 11 mm on the left side. Two
      miniscrews were inserted into the mesiobuccal side of the edentulous spaces, and
      2 more screws were inserted into the anterior sites after removing previous
      miniscrews. In addition, 4 miniscrews were inserted into the buccal and palatal
      sides between the first and second maxillary molars to intrude the maxillary
      posterior teeth, which had extruded into the missing mandibular spaces. Careful
      biomechanical consideration was used to prevent extrusion of the molars and
      worsening of the anterior open bite from protraction of the posterior teeth.
      Ultimately, the anterior open bite was corrected by both intrusion of the
      maxillary molars and extrusion of the maxillary anterior teeth. Excellent
      occlusion and correction of the anterior open bite were achieved without tipping,
      rotation of the posterior teeth, or other problems. The right mandibular third
      molar, which had been impacted at the beginning of treatment, erupted into the
      second molar space and functioned properly. At the 1-year follow-up examination,
      the patient had a slight anterior open bite, but closure of the first molar
      extraction spaces was well maintained.

PMID- 22640681
TI  - Esthetic orthodontic treatment with a double J retractor and temporary anchorage
      devices.
AB  - This clinical article reports an esthetic treatment option for managing a Class
      II malocclusion in an adult. The patient, a woman aged 24 years 2 months, had
      crowding and a convex profile. She was treated with maxillary first premolar
      extractions, a double J retractor, and temporary skeletal anchorage devices in
      the maxillary arch. Posttreatment records after 2 years showed excellent results
      with good occlusion and long-term stability.

PMID- 22640682
TI  - Construction of orthodontic setup models on a computer.
AB  - INTRODUCTION: Orthodontic setup models are usually limited to the display of
      teeth, with no information about the roots. The purpose of this article is to
      present a method for visualizing the tooth roots in setup models by integrating
      information from cone-beam computed tomography and a laser scanner. The
      reproducibility of the integration was evaluated. METHODS: The records of 5
      patients were used in this study. Three-dimensional digital models were generated
      from the dental casts. Tooth models were generated from the cone-beam computed
      tomography slices. The 3-dimensional models were superimposed on the crowns of
      the teeth in the tooth models and integrated. The integrated 3-dimensional tooth
      model and 3-dimensional setup model were registered. The reproducibility of the
      integration was evaluated for each tooth. Unpaired Student t tests were performed
      on the data between the anterior and posterior teeth, and between the right and
      left teeth. RESULTS: The discrepancy among the integrated 3-dimensional models at
      the final positions after we used this technique was 0.025 +/- 0.007 mm. There
      was a significant difference in the distance between the anterior and posterior
      teeth (P <0.05). However, the average distances between the anterior and
      posterior teeth were small: 0.023 +/- 0.007 and 0.028 +/- 0.007 mm, respectively.
      No significant difference was found between the right and left teeth (P = 0.831).
      CONCLUSIONS: The methods presented in this study provide a reproducible
      visualization of tooth roots in virtual setup models by registering accurate
      crown models to cone-beam computed tomography scans.

PMID- 22640683
TI  - Deja vu all over again: continuous treatment and the statute of limitations.

PMID- 22640684
TI  - Sample calculation for split-mouth designs.

PMID- 22640685
TI  - Treatment of a Class II Division 1 malocclusion with miniscrew anchorage.
AB  - This case report describes the treatment of a 30-year-old woman with a Class II
      Division 1 malocclusion, characterized by a large overjet, a deep overbite, and a
      V-shaped maxillary dental arch. She had a convex profile with a retrognathic
      mandible and marked lip protrusion. Treatment involved extraction of 4 first
      premolars and miniscrew implant anchorage for space closure. The total treatment
      time was about 20 months. Ideal overjet and overbite relationships were
      established, and the facial profile was improved substantially. The 2-year follow
      up records show a morphologically and functionally stable result.

PMID- 22640686
TI  - Water and sugar-sweetened beverage consumption and changes in BMI among Brazilian
      fourth graders after 1-year follow-up.
AB  - OBJECTIVE: We examined whether drinking water per se is associated with drinking
      less of other beverages and whether changes in BMI are associated with the intake
      of water and other beverages. DESIGN: Secondary analysis of a randomized trial of
      fourth graders followed over 1 year. SETTING: Public schools in the metropolitan
      area of Rio de Janeiro, Brazil. SUBJECTS: Participants were 1134 students aged 10
      11 years. RESULTS: At baseline, a higher frequency of water consumption was
      associated with a greater daily intake of fruit juice (P = 0.02) and a higher
      daily frequency of milk (P = 0.005). In the intervention group, the baseline
      frequency of water consumption was negatively associated with weight change over
      1 year but without statistical significance (coefficient = -0.08 kg/m2; 95 % CI 
      0.37, 0.24 kg/m2), whereas fruit juice intake frequency was positively associated
      with weight change: each increase in fruit juice intake of 1 glass/d was
      associated with a BMI increase of 0.16 (95 % CI 0.02, 0.30) kg/m2. CONCLUSIONS:
      Our findings do not support a protective effect of water consumption on BMI, but
      confirm consumption of juice drinks as a risk factor for BMI gain. Students who
      reported high water consumption also reported high intake of other beverages;
      therefore, the promotion of water consumption per se would not prevent excessive
      weight gain.

PMID- 22640687
TI  - Speech-in-noise measures: variable versus fixed speech and noise levels.
AB  - OBJECTIVE: The purpose was to determine if speech-recognition performances were
      the same when the speech level was fixed and the noise level varied as when the
      noise level was fixed and the speech level varied. DESIGN: A descriptive/quasi
      experimental experiment was conducted with Lists 3 and 4 of the revised speech
      perception in noise (R-SPIN) test, which involves high predictability (HP) and
      low predictability (LP) words. The R-SPIN was modified into a multiple signal-to
      noise paradigm (23- to -1-dB in 3-dB decrements) from which the 50% points were
      calculated with the Spearman-Karber equation. STUDY SAMPLE: Sixteen young
      listeners with normal hearing and 48 older listeners with pure-tone hearing
      losses participated. RESULTS: The listeners with normal hearing performed better
      than the listeners with hearing loss on both the HP and LP conditions. For both
      groups of listeners, (1) performance on the HP sentences was better than on the
      LP sentences, and (2) the mean 50% points were 0.1 to 0.4 dB lower (better) on
      the speech-variable, babble-fixed condition than on the speech-fixed, babble
      variable condition. CONCLUSIONS: For practical purposes the <= 0.4-dB differences
      are not considered noteworthy as the differences are smaller than the decibel
      value of one word on the test (0.6 dB).

PMID- 22640689
TI  - Scoring tail damage in pigs: an evaluation based on recordings at Swedish
      slaughterhouses.
AB  - BACKGROUND: There is increasing interest in recording tail damage in pigs at
      slaughter to identify problem farms for advisory purposes, but also for
      benchmarking within and between countries as part of systematic monitoring of
      animal welfare. However, it is difficult to draw conclusions when comparing
      prevalence's between studies and countries partly due to differences in
      management (e.g. differences in tail docking and enrichment routines) and partly
      due to differences in the definition of tail damage. METHODS: Tail damage and
      tail length was recorded for 15,068 pigs slaughtered during three and four
      consecutive days at two slaughterhouses in Sweden. Tail damage was visually
      scored according to a 6-point scale and tail length was both visually scored
      according to a 5-point scale and recorded as tail length in centimetres for pigs
      with injured or shortened tails. RESULTS: The total prevalence of injury or
      shortening of the tail was 7.0% and 7.2% in slaughterhouse A and B, respectively.
      When only considering pigs with half or less of the tail left, these percentages
      were 1.5% and 1.9%, which is in line with the prevalence estimated from the
      routine recordings at slaughter in Sweden. A higher percentage of males had
      injured and/or shortened tails, and males had more severely bitten tails than
      females. CONCLUSIONS: While the current method to record tail damage in Sweden
      was found to be reliable as a method to identify problem farms, it clearly
      underestimates the actual prevalence of tail damage. For monitoring and
      benchmarking purposes, both in Sweden and internationally, we propose that a
      three graded scale including both old and new tail damage would be more
      appropriate. The scale consists of one class for no tail damage, one for mild
      tail damage (injured or shortened tail with more than half of the tail remaining)
      and one for severe tail damage (half or less of the tail remaining).

PMID- 22640688
TI  - Further understanding of the comorbidity between Attention-Deficit/Hyperactivity
      Disorder and bipolar disorder in adults: an MRI study of cortical thickness.
AB  - Although Attention-Deficit/Hyperactivity Disorder (ADHD) and Bipolar Disorder
      (BPD) frequently co-occur and represent a particularly morbid clinical form of
      both disorders, neuroimaging research addressing this comorbidity is scarce. Our
      aim was to evaluate cortical thickness in ADHD and BPD, testing the hypothesis
      that comorbid subjects (ADHD+BPD) would have neuroanatomical correlates of both
      disorders. Magnetic Resonance Imaging (MRI) findings were compared between 31
      adults with ADHD+BPD, 18 with BPD, 26 with ADHD, and 23 healthy controls.
      Cortical thickness analysis of regions of interest was estimated as a function of
      ADHD and BPD status, using linear regression models. BPD was associated with
      significantly thicker cortices in 13 regions, independently of ADHD status and
      ADHD was associated with significantly thinner neocortical gray matter in 28
      regions, independent of BPD. In the comorbid state of ADHD plus BPD, the profile
      of cortical abnormalities consisted of structures that are altered in both
      disorders individually. Results support the hypothesis that ADHD and BPD
      independently contribute to cortical thickness alterations of selective and
      distinct brain structures, and that the comorbid state represents a combinatory
      effect of the two. Attention to comorbidity is necessary to help clarify the
      heterogeneous neuroanatomy of both BPD and ADHD.

PMID- 22640690
TI  - Does neovascularization predict response to statin therapy? Optical coherence
      tomography study.

PMID- 22640691
TI  - Prevalence of ventricular conduction blocks in the resting electrocardiogram in a
      general population: the Health 2000 Survey.
AB  - AIMS: The prevalence of eight different ventricular conduction blocks and their
      association with risk factors and major cardiovascular diseases were studied in a
      major Finnish population study. METHODS: Data, including 12-lead
      electrocardiograms, were collected from 6315 subjects. The prevalence of left
      bundle branch block (LBBB), right bundle branch block (RBBB), non-specific
      ventricular block, incomplete LBBB, incomplete RBBB, R-R'-pattern, left anterior
      hemiblock (LAHB), and left posterior hemiblock (LPHB) was calculated for both
      genders in three age groups. Their association with risk factors and
      cardiovascular diseases was studied. RESULTS: R-R'-pattern was the most common
      ventricular conduction block in all age groups (3.9%, p<0.001 for comparison
      between groups), but it showed no association with cardiovascular diseases. Males
      had more RBBB (1.5% vs. 0.7%, p<0.001), incomplete LBBB (1.8 vs. 0.4, p<0.001)
      and non-specific ventricular block (1.1% vs. 0.1%, p<0.001). With increasing age
      (<45 years vs. >55 years) LBBB, RBBB and LAHB (0 vs. 2.2%, 0.3 vs. 2.2%, 0.2 vs.
      1.9% respectively, p-values<0.001) became more prevalent. LBBB, RBBB and non
      specific ventricular conduction block were associated with coronary heart disease
      (angina pectoris in 28.3, 20.3 and 22.9%, respectively) and heart failure (25.0,
      10.1 and 11.4%, respectively). LBBB and RBBB were also associated with peripheral
      vascular disease (8.8%). CONCLUSIONS: Ventricular conduction blocks differ in
      prevalence between sexes and age groups. They also show disparate association
      with cardiovascular diseases. These differences need to be taken into
      consideration in everyday clinical practice.

PMID- 22640692
TI  - Serum osteoprotegerin and osteopontin levels are associated with arterial
      stiffness and the presence and severity of coronary artery disease.
AB  - BACKGROUND: Osteopontin (OPN) and osteoprotegerin (OPG) have recently emerged as
      key factors in both vascular remodeling and development of atherosclerosis.
      Arterial stiffness has an independent predictive value for cardiovascular events.
      We evaluate the relationship between OPG, OPN serum levels and vascular function
      in coronary artery disease (CAD) patients. METHODS: The study population was
      consisted of 409 subjects (280 with CAD and 129 without CAD). Carotid-femoral
      pulse wave velocity (PWV) was measured as an index of aortic stiffness. OPG and
      OPN levels were measured, as markers of vascular remodeling and calcification, by
      ELISA. Gensini score was used to evaluate the extent of CAD. RESULTS: CAD
      patients, compared to those without CAD, had higher OPG (3.91 +/- 1.87 pmol/l vs.
      2.88 +/- 1.32 pmol/l, p<0.001) and logOPN levels (1.81 +/- 0.18 ng/ml vs. 1.71 +/
      0.24 ng/ml, p<0.001) and impaired PWV (8.94 +/- 2.21 m/s vs. 8.28 +/- 1.91 m/s,
      p=0.006). Furthermore, PWV was associated with serum OPG levels (r=0.19, p<0.001)
      and with serum logOPN levels (r=0.10, p=0.049). Multivariate linear regression
      analysis revealed that increased OPG (p=0.013) and logOPN (p=0.006) levels are
      associated with 3-vessel CAD and Gensini score (p=0.04 for OPG and p=0.09 for
      OPN), independently of other known cardiovascular risk factors. CONCLUSION: The
      present study revealed that serum OPG and OPN levels are positively associated
      with arterial stiffness, and with the extent of CAD. These preliminary results
      suggest that OPG and OPN levels are significantly correlated with vascular
      function contributing to the pathogenesis of atherosclerosis in CAD. Further
      studies are needed to explore the mechanisms of action of OPG and OPN in CAD.

PMID- 22640693
TI  - Cancer patients, their caregivers and coping with loneliness.
AB  - Four hundred and twenty-six participants volunteered to participate in this
      study. A total of 159 men and 281 women comprised the sample. The sample was
      composed of 99 cancer stricken patients, 97 caregivers, 124 participants from the
      general population, and 126 people who were related to them in a similar manner
      that caregivers were related to patients (i.e. spouse, intimate partner, child,
      family member, etc.). Utilizing the Loneliness Questionnaire, the
      Multidimensional Scale of Perceived Social Support (MPSS), and the Sense of
      Coherence (SOC) questionnaires, it was found that significant differences among
      the four groups were found on Reflection and Acceptance, Self-development and
      Understanding, Social Support Network, Distancing and Denial, and on the
      Increased Activity subscales. Significant differences were not found on the
      Religion and Faith subscale. The findings are interpreted in light of the
      analyses of the other two measures which address the social support that patients
      and caregivers received and their SOC.

PMID- 22640694
TI  - Genome-wide association analyses of the 15th QTL-MAS workshop data using mixed
      model based single locus regression analysis.
AB  - BACKGROUND: The mixed model based single locus regression analysis (MMRA) method
      was used to analyse the common simulated dataset of the 15th QTL-MAS workshop to
      detect potential significant association between single nucleotide polymorphisms
      (SNPs) and the simulated trait. A Wald chi-squared statistic with df =1 was
      employed as test statistic and the permutation test was performed. For adjusting
      multiple testing, phenotypic observations were permutated 10,000 times against
      the genotype and pedigree data to obtain the threshold for declaring genome-wide
      significant SNPs. Linkage disequilibrium (LD) in term of D' between significant
      SNPs was quantified and LD blocks were defined to indicate quantitative trait
      loci (QTL) regions. RESULTS: The estimated heritability of the simulated trait is
      approximately 0.30. 82 genome-wide significant SNPs (P < 0.05) on chromosomes 1,
      2 and 3 were detected. Through the LD blocks of the significant SNPs, we
      confirmed 5 and 1 QTL regions on chromosomes 1 and 3, respectively. No block was
      detected on chromosome 2, and no significant SNP was detected on chromosomes 4
      and 5. CONCLUSION: MMRA is a suitable method for detecting additive QTL and a
      fast method with feasibility of performing permutation test. Using LD blocks can
      effectively detect QTL regions.

PMID- 22640695
TI  - Comparing Dutch case management care models for people with dementia and their
      caregivers: The design of the COMPAS study.
AB  - BACKGROUND: Dementia care in the Netherlands is shifting from fragmented, ad hoc
      care to more coordinated and personalised care. Case management contributes to
      this shift. The linkage model and a combination of intensive case management and
      joint agency care models were selected based on their emerging prominence in the
      Netherlands. It is unclear if these different forms of case management are more
      effective than usual care in improving or preserving the functioning and well
      being at the patient and caregiver level and at the societal cost. The objective
      of this article is to describe the design of a study comparing these two case
      management care models against usual care. Clinical and cost outcomes are
      investigated while care processes and the facilitators and barriers for
      implementation of these models are considered. DESIGN: Mixed methods include a
      prospective, observational, controlled, cohort study among persons with dementia
      and their primary informal caregiver in regions of the Netherlands with and
      without case management including a qualitative process evaluation. Inclusion
      criteria for the cohort study are: community-dwelling individuals with a dementia
      diagnosis who are not terminally-ill or anticipate admission to a nursing home
      within 6 months and with an informal caregiver who speaks fluent Dutch. Person
      with dementia-informal caregiver dyads are followed for two years. The primary
      outcome measure is the Neuropsychiatric Inventory for the people with dementia
      and the General Health Questionnaire for their caregivers. Secondary outcomes
      include: quality of life and needs assessment in both persons with dementia and
      caregivers, activity of daily living, competence of care, and number of crises.
      Costs are measured from a societal perspective using cost diaries. Process
      indicators measure the quality of care from the participant's perspective. The
      qualitative study uses purposive sampling methods to ensure a wide variation of
      respondents. Semi-structured interviews with stakeholders based on the
      theoretical model of adaptive implementation are planned. DISCUSSION: This study
      provides relevant insights into care processes, description of two case
      management models along with clinical and economic data from persons with
      dementia and caregivers to clarify important differences in two case management
      care models compared to usual care.

PMID- 22640696
TI  - Microfluidity mapping using fluorescence correlation spectroscopy: a new way to
      investigate plasma membrane microorganization of living cells.
AB  - Diffusion time distribution analysis has been employed to highlight the
      microfluidity fingerprint of plasma membrane of living cells. Diffusion time
      measurements were obtained through fluorescence correlation spectroscopy
      performed at the single cell level, over various eukaryotic cell lines (MCF7,
      LR73, KB3.1, MESSA and MDCKII). The nonsymmetric profile of the diffusion time
      distributions established experimentally, is discussed according to Monte Carlo
      simulations, which reproduce the diffusion of the fluorescent probe in
      heterogeneous membrane.

PMID- 22640697
TI  - Tarsal and tarsometatarsal coalitions from Mound C (Ocmulgee Macon Plateau site,
      Georgia): implications for understanding the patterns, origins, and antiquity of
      pedal coalitions in Native American populations.
AB  - Tarsal and tarsometatarsal coalitions are malsegmentation errors that result in
      incomplete division between two or more normally separate bones of the foot.
      Coalitions may be osseous, characterized by bony union, or non-osseous, in which
      the affected elements are united by fibrous tissue, cartilage, or some
      combination of both. Evidence indicates that non-osseous coalitions are
      frequently overlooked or misinterpreted in skeletal samples. The purpose of this
      study is to (1) report two non-osseous coalition cases (naviculocuneiform I, CF3
      MT3) from the Ocmulgee Mound Site in Georgia, and (2) examine the occurrence of
      coalitions throughout the foot in Native American samples relative to other major
      populations. Evidence suggests that Native Americans exhibit a pattern of
      coalitions in the foot that differs from that recently documented for European
      and African samples. Native Americans display a relatively high rate of midfoot
      and forefoot coalitions, and known cases are both geographically and temporally
      diverse. This distribution, along with evidence of similar patterns in East Asian
      samples, suggests that the pattern of coalition seen in Native Americans has
      origins in Asiatic parent populations during the late Pleistocene. Individuals
      migrating to the New World with proximal midfoot coalitions are likely to have
      endured biomechanical stress during prolonged physical activity and walking, as
      frequently seen in modern clinical cases.

PMID- 22640698
TI  - A case of EBV driven haemophagocytic lymphohistiocytosis complicating a teenage
      Crohn's disease patient on azathioprine, successfully treated with rituximab.
AB  - We report a case of Epstein-Barr virus infection with the subsequent development
      of haemophagocytic lymphohistiocytosis in a teenage Crohn's disease patient
      treated with azathioprine. We found that the early introduction of the anti-B
      cell monoclonal antibody rituximab precipitated a rapid fall in circulating B
      cells and EBV viral load, resulting in a prompt and sustained recovery from what
      is a potentially fatal complication of azathioprine therapy in Crohn's disease
      patients.

PMID- 22640700
TI  - Cyclooxygenase 2 and prostaglandin E2 regulate the attachment of calcium oxalate
      crystals to renal epithelial cells.
AB  - OBJECTIVE: To determine the roles of endogenous cyclooxygenase 2 and
      prostaglandin E(2) in crystal-cell binding, which is considered to be an
      important step in the development of intratubular nephrocalcinosis. METHODS: An
      expression plasmid for human cyclooxygenase 2 was introduced into Madin-Darby
      canine kidney cells using the lipofection method. Cyclooxygenase activity was
      measured using thin-layer chromatography, and the prostaglandin E(2)
      concentration was determined with an enzyme immunoassay. In addition, crystal
      attachment was evaluated with a liquid scintillation counter using [(14)C]
      calcium oxalate monohydrate crystals, and immunohistochemistry and an enzyme
      immunoassay were used to analyze and quantify the expression of hyaluronan, a
      crystal-binding molecule. RESULTS: Cyclooxygenase 2-overexpressing Madin-Darby
      canine kidney cells produced about 10-fold more prostaglandin E(2) than wild-type
      Madin-Darby canine kidney cells, and their hyaluronan production was also
      upregulated. The attachment of calcium oxalate monohydrate crystals to
      cyclooxygenase 2-overexpressing Madin-Darby canine kidney cells was significantly
      reduced compared with their attachment to wild-type and mock-transfected Madin
      Darby canine kidney cells. Pre-incubation of the cyclooxygenase 2-overexpressing
      cells, as well as the mock-transfected and wild-type cells with the
      cyclooxygenase 2 selective inhibitor etodolac, increased the cellular attachment
      of calcium oxalate monohydrate crystals in a dose-dependent manner. CONCLUSIONS:
      These findings suggest that cyclooxygenase 2 expression and the resultant
      increase in endogenous prostaglandin E(2), leading to increased hyaluronan
      production, help to prevent nephrocalcinosis by inhibiting the attachment of
      calcium oxalate monohydrate crystals to the surface of renal epithelial cells.

PMID- 22640699
TI  - Ethyl pyruvate attenuates formalin-induced inflammatory nociception by inhibiting
      neuronal ERK phosphorylation.
AB  - BACKGROUND: Ethyl pyruvate (EP) possesses anti-inflammatory activity. However,
      the potential anti-nociceptive value of EP for the treatment of the inflammatory
      nociception is largely unknown. We investigated whether EP could have any anti
      nociceptive effect on inflammatory pain, after systemic administration of EP (10,
      50, and 100 mg/kg, i.p.), 1 hour before formalin (5%, 50 MUl) injection into the
      plantar surface of the hind paws of rats. RESULTS: EP significantly decreased
      formalin-induced nociceptive behavior during phase II, the magnitude of paw
      edema, and the activation of c-Fos in L4-L5 spinal dorsal horn. EP also
      attenuated the phosphorylation of extracellular signal-regulated kinase (ERK) in
      the neurons of L4-L5 spinal dorsal horn after formalin injection. Interestingly,
      the i.t. administration of PD98059, an ERK upstream kinase (MEK) inhibitor,
      completely blocked the formalin-induced inflammatory nociceptive responses.
      CONCLUSIONS: These results demonstrate that EP may effectively inhibit formalin
      induced inflammatory nociception via the inhibition of neuronal ERK
      phosphorylation in the spinal dorsal horn, indicating its therapeutic potential
      in suppressing acute inflammatory pain.

PMID- 22640701
TI  - Approaching the immunophysiology of steroid resistance.

PMID- 22640702
TI  - Aberrant cortical gyrification in schizophrenia: a surface-based morphometry
      study.
AB  - BACKGROUND: Schizophrenia is considered to be a disorder of cerebral connectivity
      associated with disturbances of cortical development. Disturbances in
      connectivity at an early period of cortical maturation can result in widespread
      defects in gyrification. Investigating the anatomic distribution of gyrification
      defects can provide important information about neurodevelopment in patients with
      schizophrenia. METHODS: We undertook an automated surface-based morphometric
      assessment of gyrification on 3-dimensionally reconstructed cortical surfaces
      across multiple vertices that cover the entire cortex. We used a sample from our
      previous research of 57 patients (50 men) with schizophrenia and 41 controls (39
      men) in whom we had tested a specific hypothesis regarding presence of both hypo
      and hypergyria in the prefrontal cortex using a frontal region-of-interest
      approach. RESULTS: Regions with significant reductions in gyrification
      (hypogyria) were seen predominantly in the left hemisphere, involving the insula
      and several regions of the multimodal association cortex. Although the prefrontal
      hypergyria documented earlier did not survive the statistical correction required
      for a whole brain search (cluster inclusion at p = 0.0001), significant
      hypergyric frontal clusters emerged when the threshold was lowered (cluster
      inclusion at p = 0.05). In the insula, a reduction in gyrification was related to
      reduced cortical thickness in patients with schizophrenia. LIMITATIONS: We
      studied a sample of patients taking antipsychotic medications, which could have
      confounded the results. Our sample was predominantly male, limiting the
      generalizability of our findings. CONCLUSION: Our observations suggest that the
      disturbances in cortical gyrification seen in patients with schizophrenia might
      be related to a disrupted interaction between the paralimbic and the multimodal
      association cortex and thus might contribute to the pathogenesis of the illness.

PMID- 22640704
TI  - Tickling in juvenile but not adult female rats conditions sexual partner
      preference.
AB  - Female rats display a conditioned partner preference for males that bear odors
      paired with different types of rewarding unconditioned stimuli (UCS). Here we
      examined whether tickling constitutes a rewarding UCS that supports the
      development of partner preferences. In Experiment 1, we tested the possibility
      that odors associated with a tickling UCS in prepubescent rats would induce a
      conditioned partner preference in adulthood. Two groups were formed with 31-day
      old, single-housed females, tickled for 6 min daily for 10 days, by a hand that
      wore a scented glove (almond or lemon). At 47 days of age, females were
      ovariectomized (OVX), hormone-primed (EB+P), and tested for sexual partner
      preference with two scented stud males (one almond and one lemon). In each group,
      females displayed a sexual preference toward males bearing the odor paired with
      tickling, as observed with longer visits, more solicitations, hops & darts, and
      receiving more intromissions and ejaculations from the preferred male. In
      Experiment 2, we used 3-month old, OVX, hormone-primed rats conditioned every 4
      days for 10 trials. In contrast to juvenile females, adult females failed to
      prefer males that bore the odor paired with tickling but instead preferred the
      novel male. These results suggest that tickling has opposite age-dependent
      effects in the conditioning of partner preference. Tickling in juvenile females
      appears to act as a rewarding UCS, whereas in adult females it may act as an
      aversive UCS. Further research is needed to understand brain mechanisms that
      might account for such differences.

PMID- 22640705
TI  - How to mend a broken heart: a major stab wound of the left ventricle.
AB  - A 28-year-old male admitted with a stab wound under his left nipple, underwent
      emergency surgery because of confusion, a decreasing blood pressure and
      increasing tachycardia. A median sternotomy incision was made and after
      establishing cardiopulmonary bypass, a 7 cm wound in the left ventricle and a
      smaller wound in the left atrium were repaired. An injured segment of lung was
      resected and the left anterior descending and circumflex arteries were grafted
      after weaning from cardiopulmonary bypass was initially unsuccessful. Although
      the patient suffered a stroke, probably due to prehospital hypoperfusion, he
      eventually recovered without major sequelae. In addition to the case report we
      present a literature review of the last 15 years pertaining the management of
      penetrating cardiac injury.

PMID- 22640703
TI  - Differential effects of 3 classes of antidiabetic drugs on olanzapine-induced
      glucose dysregulation and insulin resistance in female rats.
AB  - BACKGROUND: The second-generation antipsychotic drug olanzapine is an effective
      pharmacological treatment for psychosis. However, use of the drug is commonly
      associated with a range of metabolic side effects, including glucose intolerance
      and insulin resistance. These symptoms have been accurately modelled in rodents.
      METHODS: We compared the effects of 3 distinct classes of antidiabetic drugs,
      metformin (100 and 500 mg/kg, oral), rosiglitazone (6 and 30 mg/kg, oral) and
      glyburide (2 and 10 mg/kg, oral), on olanzapineinduced metabolic dysregulation.
      After acutely treating female rats with lower (7.5 mg/kg) or higher (15 mg/kg)
      doses of olanzapine, we assessed glucose intolerance using the glucose tolerance
      test and measured insulin resistance using the homeostatic model assessment of
      insulin resistance equation. RESULTS: Both doses of olanzapine caused pronounced
      glucose dysregulation and insulin resistance, which were significantly reduced by
      treatment with metformin and rosiglitazone; however, glucose tolerance did not
      fully return to control levels. In contrast, glyburide failed to reverse the
      glucose intolerance caused by olanzapine despite increasing insulin levels.
      LIMITATIONS: We evaluated a single antipsychotic drug, and it is unknown whether
      other antipsychotic drugs are similarly affected by antidiabetic treatments.
      CONCLUSION: The present study indicates that oral hypoglycemic drugs that
      influence hepatic glucose metabolism, such as metformin and rosiglitazone, are
      more effective in regulating olanzapine-induced glucose dysregulation than drugs
      primarily affecting insulin release, such as glyburide. The current model may be
      used to better understand the biological basis of glucose dysregulation caused by
      olanzapine and how it can be reversed.

PMID- 22640706
TI  - Trends in gynecologic cancer care in North America.
AB  - Overall, there has been tremendous movement over the last decade toward
      centralization of cancer care into specialized centers. This comes from the
      recognition that multidisciplinary care, including access to opinions from
      gynecologic, medical, and radiation oncologists, can improve patient outcomes. In
      addition to this input, it is important to have access to subspecialty pathology,
      diagnostic radiology, oncology nursing, and other disciplines as necessary. The
      population-based literature on quality of care in gynecologic cancers reflects
      this movement, with many articles evaluating outcomes in terms of structural
      variables. However, the continued presence of regional and sociodemographic
      variation in outcomes suggests it is still possible to achieve significant
      improvements in survival by concentrating efforts to improve the quality of care
      provided to gynecologic cancer patients. Improved outcomes for patients with
      ovarian cancer can be achieved by continued centralization of gynecologic cancer
      care and provision of care by gynecologic oncologists in high-volume centers.
      Further study is needed to determine if cervical cancer and vulvar cancer
      outcomes can be improved with centralization. For uterine cancer, at this time
      there do not appear to be significant improvements in outcomes related to
      centralization.For all gynecologic cancers, more attention should be paid to the
      processes of care and their impact on patient outcomes. An appropriate goal for
      all health care systems is to ensure all women have access to evidence-based
      care. This is particularly important for high-risk women, older women, and
      minority women, who suffer a disproportionate amount of the gynecologic cancer
      related mortality and often do not receive evidence-based care. Clinical practice
      guidelines exist to provide guidance to clinicians as to what constitutes
      evidence-based care and to make recommendations concerning current best
      practices. Adherence to guidelines can help to reduce variations in care due to
      sociodemographic factors. As the provision of cancer care becomes more and more
      centralized, outcomes at the population level will be improved only by focusing
      on the processes of care. A look at the three North American health care systems
      shows there are issues with women having access to high-quality, timely care.
      This fundamental problem must be addressed to systematically improve health at
      the population level. Governments should strive toward the WHO goal of promoting
      health development in their populations by reducing inequalities in the access to
      health care and health promotion activities.

PMID- 22640707
TI  - Biologic therapies and personalized medicine in gynecologic malignancies.
AB  - Through advances in human genomic sequencing, the unique molecular biology that
      predisposes certain individuals to either health or disease has now been
      illuminated. Although many malignancies behave similarly on a phenotypic level,
      biologically there exist multiple layers of interconnected molecular and cellular
      pathways that may make each patient's disease significantly more unique than
      previously appreciated. In gynecologic oncology, the most progress in developing
      targeted biologics has been in the treatment of ovarian cancers. Future
      investigations will see further development in endometrial and cervical cancers.
      Technology such as whole genome sequencing can theoretically identify the
      individual tumor's genetic profile; however, identifying the priority pathways
      for therapeutic interventions and subsequent complex interactions remains a
      significant challenge. New therapeutic technologies such as siRNA and immune
      modulators will also play a promising role in the movement toward individualized
      therapies. It is hoped that the identification and use of targeted agents will
      lead to individualized care that in turn will lead to significantly improved
      outcomes manifested by more cures and better quality of life through amelioration
      of toxicities.

PMID- 22640708
TI  - Advances in surgical care.
AB  - The numerous advances in the surgical care of gynecologic oncology patients are
      allowing clinicians to offer improved quality of life while maintaining excellent
      cancer outcomes. Advances in technology and disease understanding will only
      enhance our surgical abilities beyond what can be imagined today. Surgeons have a
      responsibility to evaluate new technology critically and incorporate the
      technology into patient care safely and efficiently.

PMID- 22640709
TI  - Hereditary gynecologic cancers: risk assessment, counseling, testing and
      management.
AB  - Gynecologists and gynecologic oncologists have a major role in identifying
      patients at increased risk of inherited cancer syndromes. Awareness of the
      biological and familial risk factors is useful in this practice, and can assist
      patients and families in navigating the follow-up for these complex disorders.
      Large national and international cohorts of women with known BRCA1/2 mutations or
      high risk continue to collect data in an attempt to better understand genetic
      risk, risk modifiers, and quality-of-life impact or screening, testing and risk
      reduction strategies. The Consortium of Investigators of Modifiers of BRCA1/2 is
      beginning to identify other genetic modifiers of BRCA1/2 risk and cancer cluster
      regions in an attempt to better individualize site specific cancer risk and
      prevention strategies. The Gynecologic Oncology Group has initiated along-term
      follow-up study to the Gynecologic Oncology Group 199 protocol, which will
      continue to advance understanding of patient decisions, quality-of-life impact,
      and other genetic factors responsible for cancer initiation and progression.
      These and other large consortia are invaluable resources with massive datasets
      requiring herculean analyses that will continue to rapidly advance our present
      knowledge and management of women with hereditary cancer syndromes.

PMID- 22640710
TI  - Ovarian cancer: screening and early detection.
AB  - Ultimately, the timely diagnosis of ovarian cancer will rely on clinical judgment
      and careful analysis of presenting symptoms within the context of a thoughtful
      dialogue between the patient and her physician. Symptoms most typical of ovarian
      cancer include bloating, abdominal or pelvic pain, and difficulty eating. In some
      studies, urinary symptoms are also a common presenting symptom. When these
      symptoms occur more than 12 times per month and are of recent onset, then ovarian
      cancer should be considered as a possibility. Although most women who have these
      symptoms do not have ovarian cancer, it is important that providers include
      ovarian cancer in their differential diagnosis. Through research from the past
      decade, we now understand that there are patterns of symptoms associated with
      ovarian cancer. Importantly, we now know that ovarian cancer is not a "silent
      disease." Finally, clinicians must always listen carefully to their patients
      avoid potentially harmful delays in diagnosis. Until there is a screening test,
      awareness is best.

PMID- 22640711
TI  - Gestational trophoblastic neoplasia.

PMID- 22640712
TI  - Vulvar and vaginal cancer.
AB  - Vulvar cancer is becoming more common as the population ages and is primarily a
      disease of the elderly. Most vulvar cancers are diagnosed at a localized stage
      and can be cured with surgery and adjuvant radiotherapy. More conservative
      therapy has been the mainstay in vulvar cancer treatment, which has lessened
      short-term and long-term morbidity without sacrificing efficacy. Recent national
      and international studies continue to prove the value of sentinel lymph node
      technology, which is moving toward a new standard of care for women with early
      stage vulvar cancer. Vaginal cancer is a rare cancer that also affects elderly
      women. Prognosis is poor; however, adequate treatment can be delivered with a
      combination of external beam radiotherapy and brachytherapy, and with surgical
      resection for a select group of patients.

PMID- 22640713
TI  - Cervical cancer.
AB  - Squamous cell cervical cancer incidence and mortality have been reduced
      dramatically as a result of successful screening in many countries. The incidence
      of cervical adenocarcinoma continues to increase. There has been concentrated
      effort toward improving early detection and screening by utilizing molecular
      biomarker assays. The FIGO staging system for cervical cancer was revised in
      2009. Fertility preservation can be offered to patients with early-stage cervical
      cancer through radical trachelectomy, although radical hysterectomy remains the
      surgical standard of care. Concurrent chemotherapy with radiation has been shown
      to have a survival advantage in patients with advanced-stage disease.
      Improvements in radiation techniques and molecular targeted therapy are the
      current research venues in cervical cancer.

PMID- 22640715
TI  - Epithelial ovarian cancer.

PMID- 22640714
TI  - Endometrial cancer.
AB  - Despite the questions and barriers, the incorporation of molecular therapy into
      treatment regimens in endometrial cancer is an exciting area of investigation
      with the potential to improve outcomes. Outside of the development of a reliable
      screening test for endometrial cancer, converting the disease to a chronic state
      and improving progression-free survival is our best hope to reverse the
      concerning trend of decreasing 5-year survival for this disease.

PMID- 22640716
TI  - What is integrative oncology and can it help my patients?
AB  - Integrative oncology lends itself to the comprehensive practice of gynecologic
      oncology with multiple tools and interventions that can impact on QoL and
      survival. However, there remains a paucity of well-designed, well-powered
      randomized control trials on various CAM modalities for gynecologic cancer
      patients. The reasons for the lack of level 1 evidence include the nascent state
      of integrative medicine as a science, the limitations on CAM funding, the
      relative lack of integration of CAM practitioners into the oncology community,
      and absence of strict regulation of herbs and supplements by the US FDA. The use
      of CAM as adjunctive therapies will likely continue given the patient-driven
      trends to date, and given the evidence for at least safety and potentially
      efficacy, our patients deserve our willingness to use all possible approaches to
      improving their outcomes. Continued evolution of our ability to specifically
      measure and describe QoL will further our ability to hone in on domains most
      important to patients and their survival and allow practitioners to make patient
      specific recommendations. Multimodal programs that include physical activity,
      stress management, and diet have the potential to address demonstrated deficits
      in PWB and FWB in ovarian cancer patients which suggests a model of collaborative
      gynecologic oncology care). Integrative oncology represents a holistic approach
      to patient care whose goal is maximization of patient quantity and quality of
      life. Patients can achieve this optimal outcome through the synergy of
      conventional care, integrative modalities, lifestyle modifications, and
      supportive care. Refer to Table 4 for a listing of integrated medicine Internet
      resources.

PMID- 22640717
TI  - Gynecologic oncology.

PMID- 22640718
TI  - I grew up watching the original Star Trek, amazed at the level of medical
      technology utilized in many episodes. Introduction.

PMID- 22640719
TI  - Factors associated with high compliance/feasibility during iron and folic acid
      supplementation in a tribal area of Madhya Pradesh, India.
AB  - OBJECTIVE: To study the feasibility of iron and folic acid (IFA) supplementation
      among tribal adolescent girls and identify factors associated with high
      compliance. DESIGN: Intervention study with IFA supplementation among tribal
      adolescent girls of Bijadandi block, Mandla district, Madhya Pradesh, India.
      Girls (n 274) from twelve villages randomly selected out of 100 potential
      villages received daily tablets containing iron (iii) hydroxide polymaltose
      complex equivalent to 100 mg of elemental Fe and 350 MUg of folic acid
      (commercially available as Feritas tablets, marketed by Intas Pharmaceutical Ltd,
      India). IFA was given for 100 d and supervised by school teachers and anganwadi
      workers. Compliance was measured using cards and interviews. SETTING: Community
      based iron supplementation programme. SUBJECTS: Tribal adolescent girls aged 12
      19 years. RESULTS: In total 233 girls completed the study. Prevalence of anaemia
      was reduced from 94 % at baseline to 69 % after the intervention. Compliance rate
      (>80 tablets) was 89 %. Minor side-effects were reported by three girls, yet they
      consumed >80 tablets. Factors associated with compliance included fasting during
      the local festival (chi 2 = 72.74, df 3; P < 0.0001) and counselling (chi 2 =
      72.74, df 3; P < 0.0001). Other qualitative factors like social mobilization,
      timely supply of tablets, quality of tablets (blister pack) and availability of
      teachers and anganwadi workers were also associated with the compliance and
      feasibility. CONCLUSIONS: High compliance indicates that IFA supplementation with
      tablets is feasible among the tribal adolescent girls of Bijadandi block, Mandla
      district.

PMID- 22640720
TI  - Discovery of novel antimicrobial peptides with unusual cysteine motifs in
      dandelion Taraxacum officinale Wigg. flowers.
AB  - Three novel antimicrobial peptides designated ToAMP1, ToAMP2 and ToAMP3 were
      purified from Taraxacum officinale flowers. Their amino acid sequences were
      determined. The peptides are cationic and cysteine-rich and consist of 38, 44 and
      42 amino acid residues for ToAMP1, ToAMP2 and ToAMP3, respectively. Importantly,
      according to cysteine motifs, the peptides are representatives of two novel
      previously unknown families of plant antimicrobial peptides. ToAMP1 and ToAMP2
      share high sequence identity and belong to 6-Cys-containing antimicrobial
      peptides, while ToAMP3 is a member of a distinct 8-Cys family. The peptides were
      shown to display high antimicrobial activity both against fungal and bacterial
      pathogens, and therefore represent new promising molecules for biotechnological
      and medicinal applications.

PMID- 22640721
TI  - Pharmacological evaluation of Ipomoea asarifolia (Desr.) against carbon
      tetrachloride-induced hepatotoxicity in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ipomoeaasarifolia (Desr.) Roem. and Schult. is
      used traditionally in some parts of Africa for the treatment of a variety of
      diseases. This study attempts to validate its hepatoprotective activity by
      evaluating the prophylactic and curative properties of the methanolic extract of
      Ipomoea asarifolia (IA) leaves. MATERIALS AND METHODS: Liver damage was induced
      by administering 0.5 ml/kg of an equal mixture of carbon tetrachloride (CCl(4))
      in olive oil intraperitoneally on alternate days, for 5 days and the plant
      extract was given orally daily, for 7 days at doses of 100, 200 and 400 mg/kg.
      RESULTS: Pre-treatment with the extract significantly (P<0.05) decreased CCl(4)
      induced elevation in serum levels of alanine transaminase, aspartate
      transaminase, alkaline phosphatase, triglycerides, bilirubin and cholesterol,
      better than the standard drug silymarin at 100 mg/kg. In the curative study, IA
      significantly (P<0.05) reversed CCl(4)-induced liver damage, comparable to
      silymarin. Hepatoprotective potential was further supported by decrease in
      pentobarbitone sleeping time and improved hepatic tissue histopathology.
      CONCLUSION: These results indicate that I. asarifolia leaves have potent
      hepatoprotective activity against CCl(4)-induced hepatic damage in rats.

PMID- 22640722
TI  - Achyranthes aspera (Apamarg) leaf extract inhibits human pancreatic tumor growth
      in athymic mice by apoptosis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Achyranthes aspera (Family Amaranthacea) is used
      for cancer therapy by ayurvedic medical practitioners in India. However, due to
      the non formal nature of its use, there are no systematic studies validating its
      medicinal properties. Thus, it's utility as an anti cancer agent remains
      anecdotal. Earlier, we demonstrated A. aspera to exhibit time and dose-dependent
      preferential cytotoxicity to cultured human pancreatic cancer cells. In this
      report we validate in vivo anti tumor properties of A. aspera. MATERIALS AND
      METHODS: The in vivo anti tumor activity of leaf extract (LE) was tested by
      intraperitoneal (IP) injections into athymic mice harboring human pancreatic
      tumor subcutaneous xenograft. Toxicity was monitored by recording changes in
      behavioral, histological, hematological and body weight parameters. RESULTS:
      Dosing LE to athymic mice by I.P. injection for 32 days showed no adverse
      reactions in treated mice. Compared to the control set, IP administration of LE
      to tumor bearing mice significantly reduced both tumor weight and volume. Gene
      expression analysis using Real time PCR methods revealed that LE significantly
      induced caspase-3 mRNA (p<0.001) and suppressed expression of the pro survival
      kinase Akt-1 (p<0.05). TUNEL assay and immunohistochemistry confirmed apoptosis
      induction by activation of caspase-3 and inhibiting Akt phosphorylation in
      treated sets. These results are in agreement with RT PCR data. CONCLUSION: Taken
      together, these data suggest A. aspera to have potent anti cancer property.

PMID- 22640723
TI  - Lycopene attenuates oxidative stress and heart lysosomal damage in isoproterenol
      induced cardiotoxicity in rats: A biochemical study.
AB  - The present study was designed to investigate the cardioprotective potential of
      lycopene (LYC) on isoproterenol (ISO)-induced oxidative stress and heart
      lysosomal damage in rats. Male Sprague Dawley rats were pretreated with LYC
      (4mg/kg, p.o.) once daily for 21 days. After the treatment period, ISO (85mg/kg)
      was injected subcutaneously, once daily, to rats for 2 days. Hemodynamic
      parameters, cardiac marker enzymes, antioxidant, and oxidative stress parameters
      in serum and heart tissues were measured. ISO treated rats showed significant
      changes in heart rates, heart weights and serum lipid profiles. The activity of
      aspartate aminotranferase (AST), lactate dehydrogenase (LDH), creatine kinase-MB
      (CK-MB) and cardiac troponin T (cTnT) were increased significantly (p<0.01) in
      the serum of ISO rats. The levels of lipid peroxides (thiobarbituric acid
      reactive substances, TBARS), protein carbonyl content (PCC) and neutrophil
      infiltration marker; myeloperoxidase (MPO) were significantly (p<0.01) increased.
      In addition, the activities of lysosomal enzymes (beta-glucuronidase, beta-N
      acetylglucosaminidase, and cathepsin-d) in the serum and heart of ISO rats were
      increased significantly. Furthermore, a marked decrease in the levels of serum
      and cardiac reduced glutathione (GSH), vitamin C and cardiac enzymatic
      antioxidants; superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and
      catalase (CAT) were observed. In vitro study confirmed the strong antioxidant
      effect of LYC on total antioxidant activity. In conclusion, the present study
      demonstrated that LYC supplementation to ISO rats significantly ameliorated
      lysosomal membrane damage as well as the alterations in cardiac enzymes, lipid
      profile and oxidative stress markers. These findings revealed the
      cardioprotective effects of LYC against ISO-induced oxidative stress and
      cardiotoxicity in rats. These observed effects are mediated via antioxidant power
      and free radical scavenging activity of LYC.

PMID- 22640724
TI  - Conflict: run! Reduced Stroop interference with avoidance responses.
AB  - Conflict has been hypothesized to be aversive, triggering avoidance behaviour
      (Botvinick, 2007). To test this hypothesis, a standard Stroop task was modified
      such that avoiding was part of the response set. More precisely, participants
      were asked to move a manikin towards or away from Stroop stimuli, depending on
      the colour of the words. Results showed that the type of response (approach
      versus avoidance) modulated the Stroop congruency effect. Specifically, the
      reaction time analysis revealed that the stimulus congruency effect disappeared
      with avoidance responses, contrary to approach responses where a stimulus
      congruency effect was present. Moreover, the error data showed a reduction of the
      general congruency effect when avoiding. These results suggest that in the face
      of conflict, avoidance is the predominant response.

PMID- 22640726
TI  - Antimicrobial food packaging film based on the release of LAE from EVOH.
AB  - The aim of this work was to develop antimicrobial films for active packaging
      applications containing the natural antimicrobial compound LAE (lauramide
      arginine ethyl ester) in EVOH copolymers with different mol % ethylene contents
      (i.e. EVOH-29 and EVOH-44). EVOH-29 and EVOH-44 films were made by casting and
      incorporating 0.25%, 1%, 5%, and 10% LAE in the film forming solution (w/w with
      respect to polymer weight). Previously, the minimum inhibitory concentration
      (MIC) and the minimum bactericidal concentration (MBC) of LAE against Listeria
      monocytogenes, Escherichia coli, and Salmonella enterica were determined by a
      microdilution assay. The antimicrobial activity of the resulting films was tested
      in vitro against these microorganisms in liquid culture media. The activity of
      the films was also evaluated over time. The results showed that films containing
      5% and 10% LAE produced total growth inhibition and viable counts decreased with
      0.25% and 1% LAE. Finally, the effectiveness of the films was tested by applying
      them to an infant formula milk inoculated with L. monocytogenes and S. enterica
      and stored for 6 days at 4 degrees C. The application of films with LAE to infant
      formula milk inoculated with L. monocytogenes reduced at the end of storage
      period about 4 log in case of 10% LAE and with S. enterica reduced 3.74 log and
      3.95 log with EVOH 29 5% and 10%, respectively, and EVOH-44 5% and 10% LAE
      reduced 1 log and 3.27 log, respectively, at the end of storage. The
      antimicrobial capacity of EVOH-29 films was greater than that of EVOH-44 films in
      all the cases tested. In general, the films were more effective in inhibiting the
      growth of L. monocytogenes than S. enterica, this inhibition being more acute at
      the end of the storage time.

PMID- 22640725
TI  - Effect of active immunization against GnRH on testosterone concentration, libido
      and sperm quality in mature AI boars.
AB  - BACKGROUND: The aim of the present study was to investigate the efficacy of the
      Improvac on testosterone concentration in blood serum, sexual behavior and sperm
      quality in matured AI boars. A total of nine Danish Landrace AI boars were
      included in the analysis. METHODS: The trial period lasted for 15 weeks and was
      divided into four periods: Control period: three weeks before vaccination; Period
      I - four weeks after first vaccination; Period II - four weeks after second
      vaccination, Period III - four weeks after third vaccination. Blood and sperm
      samples were collected at weekly intervals. Freshly collected sperm samples were
      analyzed. RESULTS: Testosterone concentration correlated with libido (r = 0.531;
      p < 0.001), volume of ejaculate (r = 0.324; p < 0.001) and the percentage of
      morphologically normal spermatozoa (r = 0.207; p < 0.05). Testosterone
      concentration rised significantly (p < 0.05) in 5-6 week of trial, e. i. after
      the first dose of Improvac and after this peak the level of testosterone further
      progressively decreased (p < 0.05). CONCLUSIONS: Results from this study indicate
      that active immunization of sexually matured boars against GnRH has negative
      impact on testosterone concentration, sexual behavior, volume of ejaculate and
      total number of normal spermatozoa in ejaculate.

PMID- 22640727
TI  - Is omentectomy mandatory in the operation for ovarian cancer? Preliminary results
      in a rat study.
AB  - OBJECTIVE: To investigate whether omentectomy is required in the operation for
      ovarian cancer, in particular at the early stage. STUDY DESIGN: F344 nude rats
      were divided into two groups: one in which laparotomy and omentectomy were
      performed (primary omentectomy group, n=6) and one without omentectomy (n=12).
      Concurrently, DISS cells derived from ovarian cancer were transplanted
      intraperitoneally. After three weeks, the 12 rats without omentectomy were
      divided into two more groups: one in which the omentum was resected together with
      the tumor (sham operation/omentectomy group, n=6) and one without omentectomy
      (sham operation alone group, n=6). RESULTS: The survival of the sham operation
      alone group was shortest with a median of 35 days, while the median of the
      primary omentectomy group was 42 days. In the sham operation/omentectomy group,
      four rats survived beyond Day 90, which was significant compared with other two
      groups. The intraperitoneal findings in the primary omentectomy group revealed
      extensive disseminated foci on the mesentery and under the abdominal wall. The
      sham operation alone group was characterized by jaundice resulting from the
      compression of the biliary system at the liver hilum by the omental mass.
      Disseminated foci were not observed in the peritoneal cavity from the sham
      operation/omentectomy group. CONCLUSIONS: This study suggests the possibility
      that the omentum has a role in capturing cancer cells and suppressing further
      peritoneal dissemination. Therefore, although omentectomy is rewarding if
      disseminated foci are present in the omentum, it is suggested that the timing of
      omentectomy requires reconsideration in the absence of omental metastasis.

PMID- 22640728
TI  - Severe maternal morbidity during childbirth hospitalisation: a comparative
      analysis between the Republic of Ireland and Australia.
AB  - OBJECTIVE: To determine the population-based rates of severe maternal morbidity
      during childbirth hospitalisation and associated characteristics in the Republic
      of Ireland and to directly compare incidence rates with Australia. STUDY DESIGN:
      Retrospective cohort study of 330,955 childbirth hospitalisations between 2005
      and 2009. Using validated diagnostic criteria from Australia, we examined
      hospital discharge records (ICD-10-AM) to identify likely cases of severe
      maternal morbidity. We derived overall and category-specific morbidity incidence
      rates and examined five-year trends. Unadjusted relative risks were computed to
      assess sociodemographic and obstetric factors associated with morbidity status.
      RESULTS: The severe maternal morbidity five-year incidence rate was 1.34 per 100
      deliveries. Between 2005 and 2009, the overall rate of severe morbidity
      significantly increased from 1.31 to 1.55 cases per 100 deliveries (test for
      trend p-value <0.001). Similar to Australia, the most frequently diagnosed severe
      morbidity indicators in Ireland were blood transfusion (112.6 per 10,000
      deliveries), evacuation of haematoma (7.2 per 10,000 deliveries) and dilation and
      curettage with general anaesthesia (3.9 per 10,000 deliveries). In the Irish
      cohort, the risk of severe morbidity was more than three-fold (RR 3.48; 95% CI:
      3.06-3.95) among women carrying multiple gestations and more than four-fold (RR
      4.37; 95% CI: 3.66-5.22) among women with a stillbirth. Further, severe morbidity
      risk was 2.62 times higher among women with a pre-existing medical condition (RR
      2.62; CI 2.03-3.37). CONCLUSION: Our use of low-cost administrative data to
      identify severe maternal morbidity contributes to a growing body of international
      initiatives to inform preventive efforts. The ability to directly compare
      morbidity rates is advantageous, underscoring the need for a uniform definition
      of severe morbidity to promote accurate and reliable international comparisons.

PMID- 22640730
TI  - Effect of the prior distribution of SNP effects on the estimation of total
      breeding value.
AB  - BACKGROUND: Five main methods, commonly applied in genomic selection, were used
      to estimate the GEBV on the 15th QTLMAS workshop dataset: GBLUP, LASSO, Bayes A
      and two Bayes B type of methods (BBn and BBt). GBLUP is a mixed model approach
      where GEBV are obtained using a relationship matrix calculated from the SNP
      genotypes. The remaining methods are regression-based approaches where the SNP
      effects are first estimated and, then GEBV are calculated given the individuals'
      genotypes. METHODS: The differences between the regression-based methods are in
      their prior distributions for the SNP effects. The prior distribution for LASSO
      is a Laplace distribution, for Bayes A is a scaled Student-t distribution, and
      the Bayes B type methods have a Spike and Slab prior where only a proportion (pi)
      of SNP has an effect, following a given distribution. In this study, two
      different distributions were considered for the Bayes B type methods: (i) normal
      and (ii) scaled Student-t. They are referred here as the BBn and BBt methods,
      respectively. These prior distributions are defined by one or more parameters
      controlling their scale/rate (lambda), shape (df) or proportion of SNP with
      effect (pi). LASSO requires one (lambda); two for Bayes A (lambda, df) and Bayes
      Bn (lambda, pi); and three for Bayes Bt (lambda, df, pi). In this study, all
      parameters were estimated from the data. An extra scenario for Bayes A and BBt
      was included where df was not estimated but fixed to 4 (suffixed _4df). The
      implementation of GBLUP was done using ASREML, the heritability was also
      estimated from the data. All other methods were implemented using a MCMC
      approach. RESULTS: All Bayes A and B methods showed accuracy (correlation between
      True and Estimated BV) as high as 0.94 except for BA_4df (r = 0.91). Compared to
      the traditional BLUP using pedigree information, these methods improved the
      accuracy between 50 and 55%. GBLUP and LASSO were less accurate (0.81 and 0.85
      respectively) and the improvements were 34 and 40% compared to BLUP. CONCLUSIONS:
      Results of all methods were consistent and the accuracies for GEBV ranged between
      0.81 and 0.94. When all parameters were estimated the results were similar for
      the Bayes A and Bayes B methods. Results showed that Bayes A was more sensitive
      to the changes in the shape parameter, and the parameter changes led to change in
      the accuracy of GEBV. However BBt was more robust to the change in this
      parameter. This may be explained by the fact that BBt estimates one extra
      parameter and it can buffer against a non-proper shape parameter.

PMID- 22640731
TI  - Uncertainty in immediate vicinity of the pancreas.

PMID- 22640729
TI  - Production of 2,3-butanediol in Saccharomyces cerevisiae by in silico aided
      metabolic engineering.
AB  - BACKGROUND: 2,3-Butanediol is a chemical compound of increasing interest due to
      its wide applications. It can be synthesized via mixed acid fermentation of
      pathogenic bacteria such as Enterobacter aerogenes and Klebsiella oxytoca. The
      non-pathogenic Saccharomyces cerevisiae possesses three different 2,3-butanediol
      biosynthetic pathways, but produces minute amount of 2,3-butanediol. Hence, we
      attempted to engineer S. cerevisiae strain to enhance 2,3-butanediol production.
      RESULTS: We first identified gene deletion strategy by performing in silico
      genome-scale metabolic analysis. Based on the best in silico strategy, in which
      disruption of alcohol dehydrogenase (ADH) pathway is required, we then
      constructed gene deletion mutant strains and performed batch cultivation of the
      strains. Deletion of three ADH genes, ADH1, ADH3 and ADH5, increased 2,3
      butanediol production by 55-fold under microaerobic condition. However,
      overproduction of glycerol was observed in this triple deletion strain.
      Additional rational design to reduce glycerol production by GPD2 deletion altered
      the carbon fluxes back to ethanol and significantly reduced 2,3-butanediol
      production. Deletion of ALD6 reduced acetate production in strains lacking major
      ADH isozymes, but it did not favor 2,3-butanediol production. Finally, we
      introduced 2,3-butanediol biosynthetic pathway from Bacillus subtilis and E.
      aerogenes to the engineered strain and successfully increased titer and yield.
      Highest 2,3-butanediol titer (2.29 . l-1) and yield (0.113 g . g-1) were achieved
      by Deltaadh1 Deltaadh3 Deltaadh5 strain under anaerobic condition. CONCLUSIONS:
      With the aid of in silico metabolic engineering, we have successfully designed
      and constructed S. cerevisiae strains with improved 2,3-butanediol production.

PMID- 22640732
TI  - Is it always Crohn's disease in a patient with perianal fistulae and skip lesions
      in the colon?

PMID- 22640733
TI  - PipB2 is a substrate of the Salmonella pathogenicity island 1-encoded type III
      secretion system.
AB  - Salmonella harbors two type III secretion systems, T3SS1 and T3SS2, encoded on
      the pathogenicity islands SPI1 and SPI2, respectively. Several effector proteins
      are secreted through these systems into the eukaryotic host cells. PipB2 is a
      T3SS2 effector that contributes to the modulation of kinesin-1 motor complex
      activity. Here, we show that PipB2 is also a substrate of T3SS1. This result was
      obtained infecting human epithelial HeLa cells for 2 h and was confirmed in
      murine RAW264.7 macrophages, and rat NRK fibroblasts. Analysis at different time
      points after infection revealed that translocation of PipB2 is T3SS1-dependent in
      epithelial cells throughout the infection. In contrast, translocation into
      macrophages is T3SS1-dependent during invasion but T3SS2-dependent at later time
      points. The N-terminal 10 amino acid residues contain the signal necessary for
      translocation through both systems. These results confirm the functional overlap
      between these virulence-related secretion systems and suggest a new role for the
      effector PipB2.

PMID- 22640735
TI  - The role of annexin A1 in expression of matrix metalloproteinase-9 and invasion
      of breast cancer cells.
AB  - Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and
      metastasis of cancer cells. However, the regulatory mechanism of MMP-9 expression
      and its biological effects on breast cancer development remain obscure. In the
      current study, we examined the potential role of annexin A1 (ANXA1) in regulating
      migration and invasion in breast cancer cell lines. Both ANXA1 mRNA and protein
      are expressed in the highly invasive, hormone-insensitive human breast cancer
      cell lines MDA-MB-231 and SKBr3, but not in the hormone-responsive cell lines MCF
      7 and T47D. Downregulation of ANXA1 expression with specific small interfering
      RNAs (ANXA1 siRNA) in MDA-MB-231 cells resulted in decreased cancer cell
      migration and invasion. Ablation of ANXA1 expression decreases the expression of
      MMP-9 at both the mRNA and protein levels and also reduces the proteolytic
      activity of MMP-9 in MDA-MB-231 cells. Moreover, silencing ANXA1 also decreases
      the transcriptional activity of MMP-9 by the suppression of nuclear factor kappa
      B (NF-kappaB) activity. Collectively, these results indicate that ANXA1 functions
      as a positive regulator of MMP-9 expression and invasion of breast cancer cells
      through specific activation of the NF-kappaB signaling pathway.

PMID- 22640734
TI  - Differences in lipid deposition and adipose membrane biophysical properties from
      lean and obese pigs under dietary protein restriction.
AB  - Obesity consists in fat accumulation leading to increase in adipose cells number
      and size. Adipocyte membrane biophysical properties are critical to maintain
      cellular viability in metabolically healthy obesity. This study investigated the
      effect of the genetic background and dietary protein restriction on fat tissue
      lipid composition, adipocyte membrane fluidity and water permeability using the
      pig as experimental model. Twenty-four male pigs from distinct genotypes, lean
      and obese, were fed on normal and reduced protein diets within a 2 * 2 factorial
      arrangement (two genotypes and two diets). Backfat thickness was twofold higher
      in obese than in lean pigs but unrelated to dietary protein level. In contrast,
      total fatty acids in the subcutaneous adipose tissue were dependent on both breed
      and diet, with increased lipid content promoted by the fatty genotype and by the
      restriction of dietary protein. Adipose membranes isolated from obese pig's
      subcutaneous fat tissue showed higher permeability to water, in line with an
      increased fluidity. Moreover, the reduced content of dietary protein influenced
      positively the fluidity of adipose membranes. Neither genotype nor diet affected
      total cholesterol concentration in the adipose membranes. Membrane-saturated
      fatty acids' content was influenced by genotype, while membrane-polyunsaturated
      fatty acids, particularly from the n-6 family, was influenced by diet. The ratio
      of oleic (18:1c9)/linoleic (18:2n-6) acids was positively correlated with
      membrane fluidity. All together, these findings reinforce the genetic background
      as a determinant player on adipose membrane biophysical properties and point to
      the dietary protein level as an important factor for subcutaneous lipid
      deposition as well as for regulation of membrane function, factors that may have
      impact on human obesity and metabolic syndrome.

PMID- 22640736
TI  - PDX1 regulation of FABP1 and novel target genes in human intestinal epithelial
      Caco-2 cells.
AB  - The transcription factor pancreatic and duodenal homeobox 1 (PDX1) plays an
      essential role in pancreatic development and in maintaining proper islet function
      via target gene regulation. Few intestinal PDX1 targets, however, have been
      described. We sought to define novel PDX1-regulated intestinal genes. Caco-2
      human intestinal epithelial cells were engineered to overexpress PDX1 and gene
      expression profiles relative to control cells were assessed. Expression of 80
      genes significantly increased while that of 49 genes significantly decreased more
      than 4-fold following PDX1 overexpression in differentiated Caco-2 cells.
      Analysis of the differentially regulated genes with known functional annotations
      revealed genes encoding transcription factors, growth factors, kinases, digestive
      glycosidases, nutrient transporters, nutrient binding proteins, and structural
      components. The gene for fatty acid binding protein 1, liver, FABP1, is repressed
      by PDX1 in Caco-2 cells. PDX1 overexpression in Caco-2 cells also results in
      repression of promoter activity driven by the 0.6kb FABP1 promoter. PDX1
      regulation of promoter activity is consistent with the decrease in FABP1 RNA
      abundance resulting from PDX1 overexpression and identifies FABP1 as a candidate
      PDX1 target. PDX1 repression of FABP1, LCT, and SI suggests a role for PDX1 in
      patterning anterior intestinal development.

PMID- 22640737
TI  - Inhibition of poly(ADP-ribose) polymerase inhibits ischemia/reperfusion induced
      neurodegeneration in retina via suppression of endoplasmic reticulum stress.
AB  - Poly(ADP-ribose) polymerase (PARP) inhibitors have neuroprotective effects after
      retinal ischemia and reperfusion (I/R) injury, but mechanisms of this action are
      not clear. A second generation PARP inhibitor, GPI 15427, was administrated to
      mice to investigate the possible mechanisms underlying its neuroprotective
      effects after retinal I/R injury. Ischemia was induced by increasing intraocular
      pressure to 80-90 mm Hg for 60 min followed by reperfusion, and mice were treated
      with GPI 15427 (40 mg/kg(-1) day(-1), orally) 2 days before or 1 day after
      injury. Histopathology caused by the retinal I/R injury was estimated by TUNEL
      assay and histological analyses. Relative gene expressions were evaluated by RT
      PCR, Western blotting and immunohistological studies. GPI 15427 inhibited the
      retinal I/R-induced PARP activation and glial cell activation. GPI 15427 also
      significantly inhibited the I/R-induced neurodegeneration, as well as increase in
      TUNEL-positive cells. I/R-induced PERK-eIF2alpha-CHOP activation and Bip over
      expression were inhibited by GPI 15427, while it did not suppress I/R-induced
      CHOP over-expression and degeneration of retinal capillaries. Our results suggest
      that GPI 15427 inhibited retinal I/R-induced neurodegeneration and glial cell
      activation, and this was associated with an effect of the drug to suppress PERK
      eIF2alpha-CHOP activation and Bip over-expression. These results provide evidence
      that GPI 15427 inhibits retinal I/R injury at least in part via inhibition of
      endoplasmic reticulum stress.

PMID- 22640738
TI  - Glycogen synthase kinase 3-beta phosphorylates novel S/T-P-S/T domains in Notch1
      intracellular domain and induces its nuclear localization.
AB  - We identified two S/T-P-S/T domains (2122-2124, 2126-2128) inducing Notch
      intracellular domain (NICD) nuclear localization. The GFP-NICD (1963-2145) fusion
      protein deletion mutant without classical NLS was localized in the nucleus like
      the full length GFP-NICD. However, quadruple substitution mutant (T2122A T2124A
      S2126A T2128A) showed increased cytoplasmic localization. GSK-3beta enhanced
      nuclear localization and transcriptional activity of WT NICD but not of quadruple
      substitution mutant. In vitro kinase assays revealed that GSK-3beta
      phosphorylated S and T residues in NICD S/T-P-S/T domains. These results suggest
      that the novel S/T-P-S/T domain, phosphorylated by GSK-3beta is also involved in
      the nuclear localization of NICD as well as classical NLS.

PMID- 22640739
TI  - An alternative n-3 fatty acid elongation pathway utilising 18:3n-3 in barramundi
      (Lates calcarifer).
AB  - Desaturase and elongase are two key enzyme categories in the long-chain
      polyunsaturated fatty acid (LCPUFA) pathway that convert dietary alpha-linolenic
      acid (18:3n-3) to docosahexaenoic acid (22:6n-3). The Delta6 desaturase is
      considered as rate limiting in the conversion. In a previous study in barramundi
      we demonstrated that the desaturase had a low Delta6 activity but noted that the
      enzyme also possessed Delta8 ability that utilised 20-carbon fatty acids. This
      observation suggests that an alternative pathway may exist in the barramundi via
      elongases to form 20-carbon metabolites from 18:3n-3 to 20:3n-3 and then Delta6/8
      desaturase to 20:4n-3. Cloning of the barramundi elongation of very long-chain
      fatty acid gene (ELOVL) and heterologous expression of the corresponding elongase
      were performed to examine activity with regard to time course, substrate
      concentration and substrate preference. Results revealed that the barramundi
      elongase showed a broad range of substrate specificity including 18-carbon PUFA
      (including 18:3n-3 and 18:2n-6), 20- and 22-carbon LCPUFA, with greater activity
      towards omega-3 (n-3) than n-6 fatty acids. The findings from this study provide
      molecular evidence for an alternative n-3 fatty acid elongation pathway utilising
      18:3n-3 in barramundi.

PMID- 22640740
TI  - Mechanistic insights into human pre-mRNA splicing of human ultra-short introns:
      potential unusual mechanism identifies G-rich introns.
AB  - It is unknown how very short introns (<65 nt; termed 'ultra-short' introns) could
      be spliced in a massive spliceosome (>2.7 MDa) without steric hindrance. By
      screening an annotated human transcriptome database (H-InvDB), we identified
      three model ultra-short introns: the 56-nt intron in the HNRNPH1 (hnRNP H1) gene,
      the 49-nt intron in the NDOR1 (NADPH dependent diflavin oxidoreductase 1) gene,
      and the 43-nt intron in the ESRP2 (epithelial splicing regulatory protein 2)
      gene. We verified that these endogenous ultra-short introns are spliced, and also
      recapitulated this in cultured cells transfected with the corresponding mini
      genes. The splicing of these ultra-short introns was repressed by a splicing
      inhibitor, spliceostatin A, suggesting that SF3b (a U2 snRNP component) is
      involved in their splicing processes. The 56-nt intron containing a pyrimidine
      rich tract was spliced out in a lariat form, and this splicing was inhibited by
      the disruption of U1, U2, or U4 snRNA. In contrast, the 49- and 43-nt introns
      were purine-rich overall without any pyrimidine-rich tract, and these lariat RNAs
      were not detectable. Remarkably, shared G-rich intronic sequences in the 49- and
      43-nt introns were required for their splicing, suggesting that these ultra-short
      introns may recruit a novel auxiliary splicing mechanism linked to G-rich
      intronic splicing enhancers.

PMID- 22640741
TI  - MicroRNA-27a promotes myoblast proliferation by targeting myostatin.
AB  - MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs that play critical
      roles in skeletal muscle development as well as in regulation of muscle cell
      proliferation and differentiation. However, the role of miRNAs in myoblast
      proliferation remains poorly understood. Here we found that the expression of miR
      27a was increased during proliferation of C2C12 myoblasts. Moreover,
      overexpression of miR-27a in C2C12 cells promoted myoblast proliferation by
      reducing the expression of myostatin, a critical inhibitor of skeletal
      myogenesis. In addition, the miR-27a was confirmed to target myostatin 3'UTR by a
      luciferase reporter analysis. Together, these results suggest that miR-27a
      promotes myoblast proliferation through targeting myostatin.

PMID- 22640742
TI  - Protocatechuic aldehyde inhibits migration and proliferation of vascular smooth
      muscle cells and intravascular thrombosis.
AB  - The migration and proliferation of vascular smooth muscle cells (VSMCs) and
      formation of intravascular thrombosis play crucial roles in the development of
      atherosclerotic lesions. This study examined the effects of protocatechuic
      aldehyde (PCA), a compound isolated from the aqueous extract of the root of
      Salvia miltiorrhiza, an herb used in traditional Chinese medicine to treat a
      variety of vascular diseases, on the migration and proliferation of VSMCs and
      platelets due to platelet-derived growth factor (PDGF). DNA 5-bromo-2'-deoxy
      uridine (BrdU) incorporation and wound-healing assays indicated that PCA
      significantly attenuated PDGF-induced proliferation and migration of VSMCs at a
      pharmacologically relevant concentration (100 MUM). On a molecular level, we
      observed down-regulation of the phosphatidylinositol 3-kinase (PI3K)/Akt and the
      mitogen-activated protein kinase (MAPK) pathways, both of which regulate key
      enzymes associated with migration and proliferation. We also found that PCA
      induced S-phase arrest of the VSMC cell cycle and suppressed cyclin D2
      expression. In addition, PCA inhibited PDGF-BB-stimulated reactive oxygen species
      production in VSMCs, indicating that PCA's antioxidant properties may contribute
      to its suppression of PDGF-induced migration and proliferation in VSMCs. Finally,
      PCA exhibited an anti-thrombotic effect related to its inhibition of platelet
      aggregation, confirmed with an aggregometer. Together, these findings suggest a
      potential therapeutic role of PCA in the treatment of atherosclerosis and
      angioplasty-induced vascular restenosis.

PMID- 22640743
TI  - SIRT1 inhibits proliferation of pancreatic cancer cells expressing pancreatic
      adenocarcinoma up-regulated factor (PAUF), a novel oncogene, by suppression of
      beta-catenin.
AB  - Because we found in a recent study that pancreatic adenocarcinoma up-regulated
      factor (PAUF), a novel oncogene, induces a rapid proliferation of pancreatic
      cells by up-regulation of beta-catenin, we postulated that beta-catenin might be
      a target molecule for pancreatic cancer treatment. We thus speculated whether
      SIRT1, known to target beta-catenin in a colon cancer model, suppresses beta
      catenin in those pancreatic cancer cells that express PAUF (Panc-PAUF). We
      further evaluated whether such suppression would lead to inhibition of the
      proliferation of these cells. The ectopic expression of either SIRT1 or
      resveratrol (an activator of SIRT1) suppressed levels of beta-catenin protein and
      its transcriptional activity in Panc-PAUF cells. Conversely, suppression of SIRT1
      expression by siRNA enhanced beta-catenin expression and transcriptional
      activity. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not
      required for reduction of beta-catenin. Treatment with MG132, a proteasomal
      inhibitor, restored beta-catenin protein levels, suggesting that SIRT1-mediated
      degradation of beta-catenin requires proteasomal activity. It was reported that
      inhibition of GSK-3beta or Siah-1 stabilizes beta-catenin in colon cancer cells,
      but suppression of GSK-3beta or Siah-1 using siRNA in the presence of resveratrol
      instead diminished beta-catenin protein levels in Panc-PAUF cells. This suggests
      that GSK-3beta and Siah-1 are not involved in SIRT1-mediated degradation of beta
      catenin in the cells. Finally, activation of SIRT1 inhibited the proliferation of
      Panc-PAUF cells by down-regulation of cyclin-D1, a target molecule of beta
      catenin. These results suggest that SIRT1 activation may be a therapeutic
      strategy for treatment of pancreatic cancer cells that express PAUF via the down
      regulation of beta-catenin.

PMID- 22640744
TI  - Epigenetic mechanisms, nuclear architecture and the control of gene expression in
      trypanosomes.
AB  - The control of gene expression, and more significantly gene cohorts, requires
      tight transcriptional coordination and is an essential feature of probably all
      cells. In higher eukaryotes, the mechanisms used involve controlled modifications
      to both local and global DNA environments, principally through changes in
      chromatin structure as well as cis-element-driven mechanisms. Although the
      mechanisms regulating chromatin in terms of transcriptional permissiveness and
      the relation to developmental programmes and responses to the environment are
      becoming better understood for animal and fungal cells, it is only just beginning
      to become clear how these processes operate in other taxa, including the
      trypanosomatids. Recent advances are now illuminating how African trypanosomes
      regulate higher-order chromatin structure, and, further, how these mechanisms
      impact on the expression of major surface antigens that are of fundamental
      importance to life-cycle progression. It is now apparent that several mechanisms
      are rather more similar between animal and fungal cells and trypanosomes than it
      originally appeared, but some aspects do involve gene products unique to
      trypanosomes. Therefore, both evolutionarily common and novel mechanisms cohabit
      in trypanosomes, offering both important biological insights and possible
      therapeutic opportunity.

PMID- 22640746
TI  - Editorial comment to comparison of mortality outcomes after radical prostatectomy
      versus radiotherapy in patients with localized prostate cancer: a population
      based analysis.

PMID- 22640745
TI  - The COMT Val158 allele is associated with impaired delayed-match-to-sample
      performance in ADHD.
AB  - BACKGROUND: This study explored the association between three measures of working
      memory ability and genetic variation in a range of catecholamine genes in a
      sample of children with ADHD. METHODS: One hundred and eighteen children with
      ADHD performed three working memory measures taken from the CANTAB battery
      (Spatial Span, Delayed-match-to-sample, and Spatial Working Memory). Associations
      between performance on working memory measures and allelic variation in
      catecholamine genes (including those for the noradrenaline transporter [NET1],
      the dopamine D4 and D2 receptor genes [DRD4; DRD2], the gene encoding dopamine
      beta hydroxylase [DBH] and catechol-O-methyl transferase [COMT]) were
      investigated using regression models that controlled for age, IQ, gender and
      medication status on the day of test. RESULTS: Significant associations were
      found between performance on the delayed-match-to-sample task and COMT genotype.
      More specifically, val/val homozygotes produced significantly more errors than
      did children who carried a least one met allele. There were no further
      associations between allelic variants and performance across the other working
      memory tasks. CONCLUSIONS: The working memory measures employed in the present
      study differed in the degree to which accurate task performance depended upon
      either the dynamic updating and/or manipulation of items in working memory, as in
      the spatial span and spatial working memory tasks, or upon the stable maintenance
      of representations, as in the delay-match-to-sample task. The results are
      interpreted as evidence of a relationship between tonic dopamine levels
      associated with the met COMT allele and the maintenance of stable working memory
      representations required to perform the delayed-match-to-sample-task.

PMID- 22640747
TI  - Assessing motor unit firing rates in ALS: A diagnostic and pathophysiological
      prospect?

PMID- 22640749
TI  - Changing computational research. The challenges ahead.

PMID- 22640748
TI  - Topography of maturational changes in EEG burst spectral power of the preterm
      infant with a normal follow-up at 2 years of age.
AB  - OBJECTIVE: To quantify the electroencephalography (EEG) burst frequency spectrum
      of preterm infants by automated analysis and to describe the topography of
      maturational change in spectral parameters. METHODS: Eighteen preterm infants
      <32weeks gestation and normal neurological follow-up at 2years underwent weekly 4
      h EEG recordings (10-20 system). The recordings (n=77) represent a large
      variability in postmenstrual age (PMA, 28-36weeks). We applied an automated burst
      detection algorithm and performed spectral analysis. The frequency spectrum was
      divided into delta1 (0.5-1Hz), delta2 (1-4Hz), theta (4-8Hz), alpha (8-13Hz) and
      beta (13-30Hz) bands. Spectral parameters were evaluated as a function of PMA by
      regression analysis. Results were interpolated and topographically visualised.
      RESULTS: The majority of spectral parameters show significant change with PMA.
      Highest correlation is found for delta and theta band. Absolute band powers
      decrease with increasing PMA, while relative alpha and beta powers increase.
      Maturational change is largest in frontal and temporal region. CONCLUSIONS:
      Topographic distribution of maturational changes in spectral parameters
      corresponds with studies showing ongoing gyration and postnatal white matter
      maturation in frontal and temporal lobes. SIGNIFICANCE: Computer analysis of EEG
      may allow objective and reproducible analysis for long-term prognosis and/or
      stratification of clinical treatment.

PMID- 22640750
TI  - Mode of data elicitation, acquisition and response to surveys: a systematic
      review.
AB  - BACKGROUND: Many studies in health sciences research rely on collecting
      participant-reported outcomes and attention is increasingly being paid to the
      mode of data collection. Consideration needs to be given to the validity of
      response via different modes and the impact that choice of mode might have on
      study conclusions. OBJECTIVES: (1) To provide an overview of the theoretical
      models of survey response and how they relate to health research; (2) to review
      all studies comparing two modes of administration for subjective outcomes and
      assess the impact of mode of administration on response quality; (3) to explore
      the impact of findings for key identified health-related measures; and (4) to
      inform the analysis of multimode studies. DATA SOURCES: A broad range of
      databases (for example EMBASE, PsychINFO, MEDLINE, EconLit, SPORTDiscus, etc.)
      were chosen to allow as comprehensive a selection as possible, and they were
      searched up until the end of 2004. REVIEW METHODS: The abstracts were reviewed
      against inclusion/exclusion criteria. Full papers were retrieved for all selected
      abstracts and then screened again using more detailed inclusion criteria related
      to the measures used. Papers that were still included were reviewed in full and
      detailed data extracted. At each stage, abstracts or papers were reviewed by a
      single reviewer. RESULTS: The search strategy identified 39,253 unique
      references, of which 2156 were considered as full papers, with 381 finally
      included in the review. Two features of mode were clearly associated with bias in
      response; however, none of the features of mode was associated with changes in
      precision. How the measure was administered, by an interviewer or by the person
      themselves, was highly significantly associated with bias (p < 0.001). A
      difference in sensory stimuli was also significant (p = 0.03). When both of these
      were present the average overall bias was < 1 point on a percentage scale. In
      terms of mediating factors, there was some suggestion that there was an
      interaction between both telephone and computer for data collection and date of
      publication, supporting the theory that differences disappear as new technologies
      become commonplace. Single-item measures were also related to greater degrees of
      bias than multi-item scales (p = 0.01). Individual analysis of the Short Form
      questionnaire-36 items and Minnesota Multiphasic Personality Inventory (MMPI)
      showed a varied pattern across the different subscales, with conflicting results
      between the two types of study. None of the MMPI measures used to detect deviant
      responding showed a relationship with the mode features tested. The limits of
      agreement analysis showed how variable measures were between modes at an
      individual rather than a group mean level. LIMITATIONS: The search strategy
      covered the period up to 2004, so any new and emerging technologies were not
      included. Not all potential mode features were tested and there was limited
      information on potential mediating factors. CONCLUSIONS: Researchers need to be
      aware of the different mode features that could have an impact on their results
      when selecting a mode of data collection for subjective outcomes. Further mode
      comparison studies, which manipulate mode features and directly assess impact
      over time, would be beneficial.

PMID- 22640751
TI  - The sensorimotor and cognitive deficits in rats following 90- and 120-min
      transient occlusion of the middle cerebral artery.
AB  - Middle cerebral artery occlusion (MCAO) is the most commonly used method to study
      the neurological and histological outcomes and the pathological mechanisms of
      ischaemic stroke. The current work compares sensorimotor and cognitive deficits
      and the infarct volume in rats following a transient 90- or 120-min MCAO, which
      allows the appropriate behavioural tests to be chosen based on the goal and
      design of the experiment. In the beam-walking test, we found significant
      differences between the 90- and 120-min MCAO groups in the number of foot faults
      made with the impaired hindlimb on post-stroke days 3, 7 and 14. In the cylinder
      test, a difference between the 90- and 120-min groups was observed on post
      operation day 14. The responses to tactile and proprioceptive stimulation were
      impaired to a similar extent after 90- and 120-min MCAO in the vibrissae-evoked
      forelimb-placing and limb-placing tests. Moreover, we found significant memory
      impairment in the 120-min MCAO group 6 days after the acquisition trial. The
      brain tissue damage was significantly higher after 120-min occlusion of the MCA
      compared with 90-min occlusion; the infarct volumes were 13% and 25% of the
      contralateral hemispheres, respectively. In conclusion, both the 90- and 120-min
      occlusion models result in a significant impairment of sensorimotor, tactile and
      proprioceptive function, but memory impairment is only observed in the 120-min
      MCAO group. The beam-walking and cylinder tests detected neurological dysfunction
      after the 120-min MCAO, whereas the limb-placing and vibrissae-evoked forelimb
      placing tests were able to evaluate the neurological dysfunction in rats after 90
      and 120-min MCAO.

PMID- 22640753
TI  - Differential effects of antipsychotics on hippocampal presynaptic protein
      expressions and recognition memory in a schizophrenia model in mice.
AB  - We compared the effects of subchronic clozapine and haloperidol administration on
      the expression of SNAP-25 and synaptophysin in an animal model of schizophrenia
      based on the glutamatergic hypothesis. Mice were first treated with a non
      competitive NMDA antagonist MK-801 (0.3 mg/kg/day) or saline for 5 days, and then
      clozapine (5 mg/kg/day), haloperidol (1 mg/kg/day) or saline was administered for
      two weeks. The locomotion test, as a behavioral model of the positive symptoms of
      schizophrenia, was applied after MK-801/saline administration on day 6 for acute
      effects and after antipsychotic/saline administration on day 19 for enduring
      effects on mice activity. Memory function was assessed by the Novel Object
      Recognition (NOR) test, one day after the last day of antipsychotic/saline
      administration (day 20). Western Blotting technique was used to determine SNAP-25
      and synaptophysin expressions in the hippocampus and frontal cortex. Both
      antipsychotics reversed the enhanced locomotion effects of MK-801. MK-801 and
      haloperidol decreased recognition memory performance. On the other hand,
      clozapine did not compromise memory. It also did not reverse the negative effects
      of MK-801 on memory performance. MK-801 did not change SNAP-25 and synaptophysin
      expressions in the hippocampus and frontal cortex. Clozapine increased
      hippocampal SNAP-25, decreased hippocampal synaptophysin expression, whereas
      frontal SNAP-25 and synaptophysin expressions remained unchanged. Haloperidol had
      no effects on levels of SNAP-25 and synaptophysin in the frontal cortex and
      hippocampus. These findings support the idea that the differential effects of
      clozapine might be related to its plastic effects and synaptic reorganization of
      the hippocampus.

PMID- 22640752
TI  - The genetics of lupus: a functional perspective.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic
      component and is characterized by chronic inflammation and the production of anti
      nuclear auto-antibodies. In the era of genome-wide association studies (GWASs),
      elucidating the genetic factors present in SLE has been a very successful
      endeavor; 28 confirmed disease susceptibility loci have been mapped. In this
      review, we summarize the current understanding of the genetics of lupus and focus
      on the strongest associated risk loci found to date (P <1.0 * 10-8). Although
      these loci account for less than 10% of the genetic heritability and therefore do
      not account for the bulk of the disease heritability, they do implicate important
      pathways, which contribute to SLE pathogenesis. Consequently, the main focus of
      the review is to outline the genetic variants in the known associated loci and
      then to explore the potential functional consequences of the associated variants.
      We also highlight the genetic overlap of these loci with other autoimmune
      diseases, which indicates common pathogenic mechanisms. The importance of
      developing functional assays will be discussed and each of them will be
      instrumental in furthering our understanding of these associated variants and
      loci. Finally, we indicate that performing a larger SLE GWAS and applying a more
      targeted set of methods, such as the ImmunoChip and next generation sequencing
      methodology, are important for identifying additional loci and enhancing our
      understanding of the pathogenesis of SLE.

PMID- 22640754
TI  - The surgical management of fibrous dysplasia of bone.
AB  - The surgical management of Polyostotic Fibrous Dysplasia (FD) of bone is
      technically demanding. The most effective methods to manage the associated bone
      deformity remain unclear. The marked variation in the degree and pattern of bone
      involvement has made it difficult to acquire data to guide the surgeon's approach
      to these patients. In light of the paucity of data, but need for guidance,
      recognized experts in the management of these patients came together at the
      National Institutes of Health in Bethesda, Maryland as part of an International
      meeting to address issues related to fibrous dysplasia of bone to discuss and
      refine their recommendations regarding the surgical indications and preferred
      methods for the management of these challenging patients. The specific
      challenges, recommended approaches, and "lessons learned" are presented in hopes
      that surgeons faced with typical deformities can be guided in the surgical
      reconstruction of both children and adults with FD.

PMID- 22640755
TI  - Genomic breeding value prediction and QTL mapping of QTLMAS2011 data using
      Bayesian and GBLUP methods.
AB  - BACKGROUND: The goal of this study was to apply Bayesian and GBLUP methods to
      predict genomic breeding values (GEBV), map QTL positions and explore the genetic
      architecture of the trait simulated for the 15th QTL-MAS workshop. METHODS: Three
      methods with models considering dominance and epistasis inheritances were used to
      fit the data: (i) BayesB with a proportion pi = 0.995 of SNPs assumed to have no
      effect, (ii) BayesCpi, where pi is considered as unknown, and (iii) GBLUP, which
      directly fits animal genetic effects using a genomic relationship matrix.
      RESULTS: BayesB, BayesCpi and GBLUP with various fitted models detected 6, 5, and
      4 out of 8 simulated QTL, respectively. All five additive QTL were detected by
      Bayesian methods. When two QTL were in either coupling or repulsion phase, GBLUP
      only detected one of them and missed the other. In addition, GBLUP yielded more
      false positives. One imprinted QTL was detected by BayesB and GBLUP despite that
      only additive gene action was assumed. This QTL was missed by BayesCpi. None of
      the methods found two simulated additive-by-additive epistatic QTL. Variance
      components estimation correctly detected no evidence for dominance gene-action.
      Bayesian methods predicted additive genetic merit more accurately than GBLUP, and
      similar accuracies were observed between BayesB and BayesCpi. CONCLUSIONS:
      Bayesian methods and GBLUP mapped QTL to similar chromosome regions but Bayesian
      methods gave fewer false positives. Bayesian methods can be superior to GBLUP in
      GEBV prediction when genomic architecture is unknown.

PMID- 22640756
TI  - Behavioral addictions: where to draw the lines?
AB  - Behavioral addictions can present in a variety of subtle and deceptive patterns.
      Because of the intense shame, guilt, and embarrassment felt by patients, it may
      fall to providers to utilize screening tools and deeper interviewing techniques
      to uncover the extent of these behaviors. Identifying when the line is crossed
      from recreation/habit to psychopathology relies on understanding current
      diagnostic criteria and consideration of cultural, ethnic, and local community
      standards. Individuals are also likely to cross back and forth between this line
      of pathology and habit, further clouding provider's opinions of diagnosis;
      therefore, tracking and monitoring these symptoms over time is critical to
      establishing patterns of use and documenting ongoing consequences. Treatment for
      these conditions is emerging slowly, and treatment outcomes for these conditions
      appear to be similar to those with other addictive disorders.

PMID- 22640757
TI  - Advances in opioid antagonist treatment for opioid addiction.

PMID- 22640758
TI  - State of the art treatments for cannabis dependence.
AB  - The treatment of cannabis dependence can be viewed as a cup half empty or half
      full. On the one hand, few people who might benefit from treatment actually
      receive it. Among those who undergo treatment in randomized trials, long-term
      abstinence is achieved by fewer than 20%. Moderate use goals have been associated
      with decreases in consequences, but the differential impact of such goals on the
      long-term course of cannabis dependence is unknown. Optimal duration of treatment
      is unclear, and certain populations, particularly patients with co-occurring
      disorders, have not been studied adequately. Twelve-step programs are low cost,
      effective for other substance use disorders, and readily available in most
      regions of the world. However, their role and efficacy in cannabis dependence has
      not been examined. Finally, effective pharmacologic treatments are under
      development, but none have yet been firmly established. On the other hand,
      psychotherapeutic strategies used to treat other substance use disorders can be
      effective for cannabis dependence. A recent meta-analysis of psychosocial
      interventions for illicit substance use disorders found that treatments for
      cannabis dependence had comparatively larger effect sizes than treatments for
      other substance use disorders. Combination therapies have proven most effective,
      particularly those that begin with a motivational intervention, utilize
      incentives to enhance the commitment to change, and teach behavioral and
      cognitive copings skills to prevent relapse. Among adolescents, family engagement
      and collaboration with community stakeholders adds substantial value. Although
      only 9% of cannabis users develop cannabis dependence, the volume of people who
      smoke cannabis ensures that the total number of people in need of help is larger
      than the capacity of substance abuse specialty services. Thus, although efforts
      to refine and improve the efficacy of treatment interventions continue,
      innovations that increase the availability and accessibility of treatment are
      also needed. Computer- and phone-based interventions, social media, and brief
      interventions that can be implemented in primary care settings are areas that may
      hold promise for reaching at-risk populations. Adolescents and persons with co
      occurring mental illness are at particularly high risk of cannabis dependence,
      and may suffer disproportionately from cannabis's adverse effects. As in the
      treatment of other substance use disorders, there is a need for a continuing care
      model with long-term follow-up that extends past the periods typically evaluated
      in treatment studies. Additionally, there is a need for further investigation of
      genetic underpinnings and endophenotypes underlying cannabis dependence to
      identify neurobiological mechanisms for targeted intervention. One benefit of the
      societal focus on cannabis has been a prominent increase in research covering
      everything from the basic science to public health impact of cannabis. Over the
      next decade, physicians who provide treatment for individuals with cannabis
      dependence are likely to see their armamentarium of effective interventions
      expand, to the ultimate betterment of patients, their families, and society at
      large.

PMID- 22640759
TI  - New systems of care for substance use disorders: treatment, finance, and
      technology under health care reform.
AB  - This article outlined ways in which persons with addiction are currently
      underserved by our current health care system. However, with the coming broad
      scale reforms to our health care system, the access to and availability of high
      quality care for substance use disorders will increase. Addiction treatments will
      continue to be offered through traditional substance abuse care systems, but
      these will be more integrated with primary care, and less separated as treatment
      facilities leverage opportunities to blend services, financing mechanisms, and
      health information systems under federally driven incentive programs. To further
      these reforms, vigilance will be needed by consumers, clinicians, and policy
      makers to assure that the unmet treatment needs of individuals with addiction are
      addressed. Embedded in this article are essential recommendations to facilitate
      the improvement of care for substance use disorders under health care reform.
      Ultimately, as addiction care acquires more of the "look and feel" of mainstream
      medicine, it is important to be mindful of preexisting trends in health care
      delivery overall that are reflected in recent health reform legislation. Within
      the world of addiction care, clinicians must move beyond their self-imposed
      "stigmatization" and sequestration of specialty addiction treatment. The problem
      for addiction care, as it becomes more "mainstream," is to not comfortably feel
      that general slogans like "Treatment Works," as promoted by Substance Abuse and
      Mental Health Services Administration's Center for Substance Abuse Treatment
      during its annual Recovery Month celebrations, will meet the expectations of
      stakeholders outside the specialty addiction treatment community. Rather, the
      problem is to show exactly how addiction treatment works, and to what extent it
      works-there have to be metrics showing changes in symptom level or functional
      outcome, changes in health care utilization, improvements in workplace attendance
      and productivity, or other measures. At minimum, clinicians will be required to
      demonstrate that their new systems of care and future clinical activity are in
      conformance with overall standards of "best practice" in health care.

PMID- 22640760
TI  - Serotonergic hallucinogens and emerging targets for addiction pharmacotherapies.
AB  - Only time will tell if serotonergic hallucinogen-assisted psychotherapy treatment
      paradigms for SUDs will prove to be safe and effective in double-blind, placebo
      controlled clinical trials. If they are, they would truly constitute a novel
      psychopharmacologic-psychosocial treatment paradigm to treat addictive disorders,
      although the risk of adverse psychological events would have to be controlled
      through a careful screening process and the risk of misuse of the substances or
      developing use syndromes would have to be considered, although the overall risk
      would be low because, as mentioned, SHs are unlike all other drugs of abuse in
      that they do not appear to produce dependence syndromes. There effects on the NA
      and DA range from inhibition to slight activation, all this without producing
      addiction. The ability of these medicinal tools to treat a range of addictive,
      psychiatric, and existential disorders is remarkable in scope and possibility.
      They truly represent a potential paradigmatic shift within the field of
      psychiatry, too interesting to not explore further.

PMID- 22640761
TI  - Drug treatments in criminal justice settings.
AB  - The available evidence suggests that drug treatment can lead to modest, but real,
      reductions in criminal offending for drug-using criminal offenders. Considering
      the scope of the problem of drug-related crime and the expense of dealing with
      these issues, even marginal improvements can lead to important aggregate savings
      in both economic and humanitarian terms. More randomized, controlled trials of
      drug treatment in criminal justice programs will lead to a more sophisticated
      understanding of what kind of treatment works best for this group.

PMID- 22640762
TI  - Managing co-occurring substance use and pain disorders.
AB  - The safest pain treatment strategy for an individual at risk or recovering from
      addiction is a nonopioid and benzodiazepine-free approach. If an opioid treatment
      is necessary, the extent of the risk can be stratified by the use of a
      biopsychosocial assessment and opioid screening tools. Individuals at high risk
      should have the greatest amount of structure and monitoring. A written informed
      consent and treatment agreement can provide a framework for the patient and the
      patient's family, as well as the clinician. The structure of treatment should
      specify only that one prescribing physician will write a limited supply of
      opioids, without refills, until the analgesic efficacy, adverse events, and goals
      for functional restoration can be assessed. An additional recommendation is that
      prescriptions should be filled at the same pharmacy with no refill by phone or
      opportunity for replacement because of loss, damage, or stolen medications.
      Additionally, random urine drug screens and PDMP reports obtained will help
      determine if the patient is taking other substances, as well as monitor the
      patient's medication use patterns. It is important to assess for risk factors in
      treating chronic pain with opioids; clinicians need to have a realistic
      appreciation of the resources available to them and the types of patients that
      can be managed in their practice. Chronic pain treatment with opioids should not
      be undertaken in patients who are currently addicted to illicit substances or
      alcohol. With the support of family and friends, ideally the patient can be
      motivated to participate in an intensive substance abuse treatment. In patients
      without an immediate risk, precautionary steps should be taken when prescribing
      opioids. Clinicians and patients need to review the risk factors for opioid
      related problems including younger age, benzodiazepine use, and comorbid
      conditions such as depression, anxiety, and heavy smoking. Both the provider and
      the patient need a personal investment in the treatment plan and protocol to
      increase the safety of opioid treatment. New medications and treatment monitoring
      are being developed to provide maximal relief for the patient while protecting
      the public health. The optimal ingredients for safe opioid treatment include a
      strong provider-patient relationship and clinician training in the assessment and
      treatment of addiction and pain.

PMID- 22640763
TI  - Clinical implications of drug abuse epidemiology.
AB  - Research on the epidemiology of illicit drug use disorders provides continued
      critical insights into the distribution and determinants of drug use and drug use
      disorders in the United States. This research serves as a foundation for
      understanding the etiology of these disorders, helping to disentangle the complex
      interrelationship of developmental, genetic, and environmental risk and
      protective factors. Building on an understanding of this research in substance
      abuse epidemiology, it is important for clinicians to understand the unique
      trends in drug use in the overall communities that they serve and the unique risk
      factors for given individuals. The generally high prevalence of substance use
      disorders, along with their high comorbidity with other psychiatric disorders and
      with the HIV epidemic, make prevention, evaluation, and referral for treatment
      for drug abuse an important part of routine clinical practice in a range of
      clinical settings, including primary care, psychiatric, and emergency department
      settings. Ongoing efforts to ensure insurance coverage parity for the treatment
      of mental health and substance use disorders offer the promise of continued
      improvements in the integration and availability of such services in the broader
      US health care system.

PMID- 22640765
TI  - Treatment of opioid dependence in the setting of pregnancy.
AB  - Opioid dependence in the setting of pregnancy provides a distinct set of
      challenges for providers. Treatment plans must take into consideration
      psychiatric and medical comorbidities while balancing risks and benefits for the
      maternal-fetal dyad. Treatment is best offered through a comprehensive treatment
      program designed to effectively deliver opioid agonist maintenance treatment
      along with psychosocial and obstetric care. As misuse of prescription analgesics
      increases in the United States, identification of the problem in pregnancy will
      become more important because this misuse is expected to lead to an increased
      prevalence of opioid dependence in pregnancy. Buprenorphine as maintenance
      treatment of opioid dependence during pregnancy has promise and may offer some
      benefits, but more research is needed, especially regarding induction of actively
      addicted women during pregnancy. For the present, methadone maintenance remains
      the standard of care for agonist treatment of opioid dependence in pregnancy
      against which other treatments must be compared.

PMID- 22640764
TI  - Psychostimulant treatment of cocaine dependence.
AB  - The use of stimulant medications for the treatment of cocaine dependence is an
      evolving scientific line of research. To date, the most promising results are
      with the higher-potency medications, the amphetamine analogues, or a combination
      of a dopaminergic medication with a contingency management behavioral
      intervention. The development of effective pharmacotherapies for opioid and
      nicotine dependence using an agonist replacement approach suggests that these
      promising findings needs to continue to be vigorously investigated. In clinical
      trial reports, there are very few instances of cardiovascular adverse events,
      which suggests that for well-selected patients with cocaine dependence, stimulant
      replacement therapy can be safe. However, clinical trial eligibility criteria
      excludes most high-risk patients from participating, and introducing stimulant
      substitution to the wider treatment community would likely expose more vulnerable
      patients to the medical risks associated with stimulant treatment while using
      cocaine. As treatment development research moves forward, attention must be paid
      to helping clinicians select patients who are most likely to benefit from
      stimulant substitution treatment and how to identify those at risk. An additional
      concern with the use of stimulant medication treatment of cocaine dependence is
      prescribing controlled substances for patients with active substance use
      disorders. Again, within a clinical trial, medication supplies are monitored and
      distributed carefully in small quantities. In a community setting, misuse or
      diversion will be risks associated with prescribing controlled substances to
      patients with addictive disorders, but therapeutic strategies for monitoring and
      limiting that risk can be implemented. Psychostimulant pharmacotherapy is a
      promising line of research for the treatment of cocaine dependence, a condition
      for which no effective pharmacotherapy has been identified. Further research is
      required to confirm positive results from single-site trials, in particular the
      study of amphetamines as a treatment for cocaine dependence. As this literature
      evolves, strategies to manage the risk of prescribing controlled substances to
      patients with addictive disorders need to be tested and refined. Biases against
      using controlled substances as a treatment for cocaine dependence should be
      challenged, much in the way the use of agonist treatment transformed the
      treatment of opioid dependence despite initial resistance from the field.

PMID- 22640766
TI  - Training the next generation of providers in addiction medicine.
AB  - Within the United States there exists a profound discrepancy between the
      significant public health problem of substance abuse and the access to treatment
      for addicted individuals. Part of the insufficient access to treatment is a
      function of relatively low levels or professional experts in addiction medicine.
      Part of the low levels of professional addiction experts is the result of
      inadequate addiction medicine training of medical students and residents. This
      article outlines deficits in addiction medicine training among medical students
      and residents, yet real change in the addiction medicine training process will
      always be subject to the complexity of producing alterations across multiple
      credentialing institutions as well as the keen competition between educators for
      "more time" for their particular subject. Other hurdles include the broad-based
      issue of stigma regarding alcoholism and other substance abuse that likely impact
      all systems that regulate physician addiction medicine training. As noted in the
      discussion of psychiatry residency, even psychiatry residents manifest stigma
      regarding substance abusing patients. Five currently active processes may allow
      for fundamental change to the inertia in physician addiction medicine training
      while also potentially impacting stigma: 1. We appear to be at the beginning of
      the integration of addiction into traditional medicine through the formation of a
      legitimized addiction medicine subspecialty. 2. The training of primary care
      trainees and practitioners in the use of SBIRT is accelerating, thus creating
      another process of addiction integration into traditional medicine. 3. The PCMH
      is being established as a model for primary care 4. The Paul Wellstone and Pete
      Domenici Mental Health Parity and Addiction Equity Act of 2008 (MHPAEA) became
      effective for group health care plan years beginning on or after July 1, 2010;
      thereby, substance abuse benefits and cost are to be the same as general medical
      or surgical benefits. 5. The equalizer is prescription drug abuse, which is
      increasing recognition of addiction among populations where it was previously
      ignored or denied. The first three activities will create a medical office
      "experience" that is largely unknown but carries the power to change the
      perception of addiction: patients visiting their primary care physicians, who
      then screen them for addiction problems and give the same attention to treatment
      and prevention of addiction problems as they might give to treatment and
      prevention of cardiovascular disease and other medical issues. The personal
      experience of the aforementioned medical scene by members of US society may also
      provide a very positive impact on psychiatrists, including those who specialize
      in addiction medicine. It is quite possible that the recognition of addiction
      medicine as a traditional medical subspecialty as well as the integration of
      addiction throughout medicine will precede any substantive change in the
      integration of mental health care with the rest of medicine. Yet, any integration
      of addiction within the entire field of medicine may open a path for mental
      health to follow. Psychiatrists, including those who are addiction experts, need
      to be a part of this new medical integration process. Being a part of new
      treatment models is why we proposed six future skillsets for psychiatrists who
      specialize in addiction. The selection of these proposed skillsets anticipates an
      integrated health care team utilizing some form of a patient-centered approach
      three are skillsets that are already required, while the last three address new
      skillsets that will be helpful in working with the integrative health care team
      model. Whatever form the future of addiction care takes, psychiatrists who
      specialize in addiction medicine can provide positive and core contributions as
      expert addiction and mental health consultants including: 1. How does one screen
      for major depression and/or an anxiety disorder and also determine a diagnosis?
      2. In prescribing, what constitutes legitimate follow-up of patients on
      antidepressants and antianxiety agents, including how to avoid additional
      substance abuse problems when prescribing sedative-hypnotics? 3. When and how
      should patients be referred to a psychiatrist? Finally, it is important to note
      that any of the potential changes described in this article need to influence
      only 10% of the approximately 17 million current heavy drinkers to seek treatment
      to equal the approximately 1.7 million heavy drinkers who are now in treatment,
      let alone any of the approximately 50 million current at-risk drinkers, virtually
      none of whom are in treatment. Among other social changes that will alter the
      future of addiction treatment, the integration of addiction into traditional
      medicine may go a long way in altering the current ratios of who seeks treatment
      and is willing to participate in treatment.

PMID- 22640767
TI  - Advances in the psychosocial treatment of addiction: the role of technology in
      the delivery of evidence-based psychosocial treatment.
AB  - The clinical community has a growing array of psychosocial interventions with a
      strong evidence base available for the treatment of SUDs. Considerable
      opportunity exists for leveraging technology in the delivery of evidence-based
      interventions to promote widespread reach and impact of evidence-based care. Data
      from this line of research to date are promising, and underscore the potential
      public health impact of technology-based therapeutic tools. To fully realize the
      potential of technology-delivered interventions, several areas of inquiry remain
      important. First, scientifically sound strategies should be explored to ensure
      technology-based interventions are optimally designed to produce maximal behavior
      change. Second, efficient and effective methods should be identified to integrate
      technology-based interventions into systems of care in a manner that is most
      responsive to the needs of individual users. Third, payment, privacy, and
      regulatory systems should be refined and extended to go beyond electronic medical
      records and telehealth/distance care models, and support the deployment of
      technology-based systems to enhance the quality, efficiency and cost
      effectiveness of care. Fourth, the mechanisms underlying behavior change derived
      from technology-based treatments should be explicated, including new mechanisms
      that may be tapped via novel, technology-based tools. Such work will be critical
      in isolating mechanisms that are useful in predicting treatment response, and in
      ensuring that key ingredients are present in technology-based interventions as
      they are made widely available.

PMID- 22640769
TI  - Neurobiology of addiction: insight from neurochemical imaging.
AB  - Neuroimaging studies have been crucial in understanding changes in the various
      neurotransmitter systems implicated in addiction in the living human brain.
      Predominantly reduced striatal dopamine transmission appears to play an important
      role in psychostimulant, alcohol and heroin addiction, while addiction to
      cannabis may be mediated primarily by the endocannabinoid system. However, the
      study of other neurotransmitter systems likely involved in addiction, for example
      glutamate, has been limited by the number and quality of available radiotracers,
      and data on changes in these systems in the most common addictions are emerging
      only now. Further studies are needed to understand fully how the interplay of
      various neurotransmitter systems contributes to addiction and to ultimately help
      to develop more effective treatment approaches.

PMID- 22640770
TI  - Expanding treatment potential for substance use disorders.

PMID- 22640768
TI  - The genetic basis of addictive disorders.
AB  - Addictions are common, chronic, and relapsing diseases that develop through a
      multistep process. The impact of addictions on morbidity and mortality is high
      worldwide. Twin studies have shown that the heritability of addictions ranges
      from 0.39 (hallucinogens) to 0.72 (cocaine). Twin studies indicate that genes
      influence each stage from initiation to addiction, although the genetic
      determinants may differ. Addictions are by definition the result of gene *
      environment interaction. These disorders, which are in part volitional, in part
      inborn, and in part determined by environmental experience, pose the full range
      of medical, genetic, policy, and moral challenges. Gene discovery is being
      facilitated by a variety of powerful approaches, but is in its infancy. It is not
      surprising that the genes discovered so far act in a variety of ways: via altered
      metabolism of drug (the alcohol and nicotine metabolic gene variants), via
      altered function of a drug receptor (the nicotinic receptor, which may alter
      affinity for nicotine but as discussed may also alter circuitry of reward), and
      via general mechanisms of addiction (genes such as monoamine oxidase A and the
      serotonin transporter that modulate stress response, emotion, and behavioral
      control). Addiction medicine today benefits from genetic studies that buttress
      the case for a neurobiologic origin of addictive behavior, and some general
      information on familially transmitted propensity that can be used to guide
      prevention. A few well-validated, specific predictors such as OPRM1, ADH1B,
      ALDH2, CHRNA5, and CYP26 have been identified and can provide some specific
      guidance, for example, to understand alcohol-related flushing and upper GI cancer
      risk (ADH1B and AKLDH2), variation in nicotine metabolism (CYP26), and,
      potentially, naltrexone treatment response (OPRM1). However, the genetic
      predictors available are few in number and account for only a small portion of
      the genetic variance in liability, and have not been integrated into clinical
      nosology or care.

PMID- 22640771
TI  - Is air trapping really a determinant of persistent airway obstruction in
      asthmatics?

PMID- 22640772
TI  - A generalised module for the selective extracellular accumulation of recombinant
      proteins.
AB  - BACKGROUND: It is widely believed that laboratory strains of Escherichia coli,
      including those used for industrial production of proteins, do not secrete
      proteins to the extracellular milieu. RESULTS: Here, we report the development of
      a generalised module, based on an E. coli autotransporter secretion system, for
      the production of extracellular recombinant proteins. We demonstrate that a wide
      variety of structurally diverse proteins can be secreted as soluble proteins when
      linked to the autotransporter module. Yields were comparable to those achieved
      with other bacterial secretion systems. CONCLUSIONS: The advantage of this module
      is that it relies on a relatively simple and easily manipulated secretion system,
      exhibits no apparent limitation to the size of the secreted protein and can
      deliver proteins to the extracellular environment at levels of purity and yields
      sufficient for many biotechnological applications.

PMID- 22640774
TI  - Neoadjuvant therapy of renal cell carcinoma: a novel treatment option in the era
      of targeted therapy?
AB  - The study was carried out to evaluate the effectiveness, toxicity and optimal
      duration of neoadjuvant therapy for patients with organ-confined or locally
      advanced renal cell carcinoma in the era of targeted agents. A literature review
      was carried out using Medline/Pubmed articles, as well as congress reports from
      the last five American Society of Clinical Oncology, American Urological
      Association and European Association of Urology Annual Meetings. Neoadjuvant
      targeted therapy is feasible and shows toxicity similar to that seen in a
      palliative setting. Most studies recommend an application for 2-4 months. The
      current data situation is best for sunitinib. Surgery can apparently be carried
      out the day right after discontinuing the drug. However, even sunitinib leads to
      only a mean 10% decrease in primary tumor size, and one-quarter to one-fifth of
      all patients show local tumor progression during treatment. Few patients
      (approximately 12%) with a vena cava tumor thrombus achieve a significant
      decrease in its level under neoadjuvant therapy; here too, progression is
      observed in a significant number of cases. Even the new targeted agents show
      limited effectiveness in achieving relevant remissions of the primary tumor.
      Furthermore, tumor progression is seen in a significant percentage of patients
      during neoadjuvant therapy. Thus, even today in the era of targeted agents, a
      neoadjuvant approach should only be made in patients with localized or locally
      advanced renal cell carcinoma, which primarily seem to be absolutely inaccessible
      by (partial) nephrectomy.

PMID- 22640773
TI  - Activation of dorsolateral prefrontal cortex in a dual neuropsychological
      screening test: an fMRI approach.
AB  - BACKGROUND: The Kana Pick-out Test (KPT), which uses Kana or Japanese symbols
      that represent syllables, requires parallel processing of discrete (pick-out) and
      continuous (reading) dual tasks. As a dual task, the KPT is thought to test
      working memory and executive function, particularly in the prefrontal cortex
      (PFC), and is widely used in Japan as a clinical screen for dementia.
      Nevertheless, there has been little neurological investigation into PFC activity
      during this test. METHODS: We used functional magnetic resonance imaging (fMRI)
      to evaluate changes in the blood oxygenation level-dependent (BOLD) signal in
      young healthy adults during performance of a computerized KPT dual task
      (comprised of reading comprehension and picking out vowels) and compared it to
      its single task components (reading or vowel pick-out alone). RESULTS: Behavioral
      performance of the KPT degraded compared to its single task components.
      Performance of the KPT markedly increased BOLD signal intensity in the PFC, and
      also activated sensorimotor, parietal association, and visual cortex areas. In
      conjunction analyses, bilateral BOLD signal in the dorsolateral PFC (Brodmann's
      areas 45, 46) was present only in the KPT. CONCLUSIONS: Our results support the
      central bottleneck theory and suggest that the dorsolateral PFC is an important
      mediator of neural activity for both short-term storage and executive processes.
      Quantitative evaluation of the KPT with fMRI in healthy adults is the first step
      towards understanding the effects of aging or cognitive impairment on KPT
      performance.

PMID- 22640775
TI  - Food as a reward in the classroom: school district policies are associated with
      practices in US public elementary schools.
AB  - The use of food as a reward for good student behavior or academic performance is
      discouraged by many national organizations, yet this practice continues to occur
      in schools. Our multiyear cross-sectional study examined the use of food as a
      reward in elementary schools and evaluated the association between district
      policies and school practices. School data were gathered during the 2007-2008,
      2008-2009, and 2009-2010 school years via mail-back surveys (N=2,069) from
      respondents at nationally representative samples of US public elementary schools
      (1,525 unique schools, 544 of which also participated for a second year). During
      every year, the corresponding district policy for each school was gathered and
      coded for provisions pertaining to the use of food as a reward. School practices
      did not change over time and as of the 2009-2010 school year, respondents in
      42.1% and 40.7% of schools, respectively, indicated that food was not used as a
      reward for academic performance or for good student behavior. In multivariate
      logistic regression analyses controlling for school characteristics and year,
      having a district policy that prohibited the use of food as a reward was
      significantly associated with school respondents reporting that food was not used
      as a reward for academic performance (P<0.05) or for good student behavior
      (P<0.05). School-level respondents in the West and the Midwest were less likely
      to report that food was not used as a reward than were respondents in the South
      and Northeast. As of 2009-2010, only 11.9% of the districts in our study
      prohibited the use of food as a reward. Strengthening district policies may
      reduce the use of food rewards in elementary schools.

PMID- 22640776
TI  - Putamen neurons process both sensory and motor information during a complex task.
AB  - The putamen has classically been considered to be primarily a motor structure. It
      is involved in a broad range of roles and its neurons have been postulated to
      function as pattern classifiers of behaviourally significant events. However, its
      specific role in motor and sensory processing is still unclear. For the purpose
      of better categorizing putamen neurons, we trained two rhesus monkeys to perform
      multisensory operant tasks by using complex stimuli such as short videoclips.
      Trials involved image or soundtrack or both. Some stimuli required a motor
      response associated to reward, whereas others did not require response and
      produced no reward. We found that neurons in the putamen showed pure visual
      responses, action-related activity, and reward responses. Insofar as action
      related activity, preparation of movement, movement execution, and withholding of
      movement involved three different putamen neuron populations. Moreover, our data
      suggest an involvement of putamen neurons in processing primary rewards and
      visual events in a complex task, which may contribute to reinforcement learning
      through stimulus-reward association.

PMID- 22640777
TI  - Complexities of pain assessment and management in hospitalised older people: a
      qualitative observation and interview study.
AB  - BACKGROUND: Pain continues to be a common problem for older hospitalised
      patients, but little is known about how the complexities of actual clinical
      practice affect pain assessment and management in these patients. OBJECTIVE: To
      examine how pain was assessed and managed in older patients who were admitted to
      geriatric evaluation and management units. DESIGN, SETTING AND PARTICIPANTS: A
      naturalistic observational research design was used involving observations of
      interactions between nurses and patients, and follow-up interviews with nurses.
      Three observation periods were conducted between midnight and midday, which
      commenced at 03:30, 07:30, and 10:30, and three observation periods were
      conducted between midday and midnight, which commenced at 15:30, 18:30, and
      22:30. Between 12 and 13 observations were conducted for each observation period,
      each ranging from 2 to 3h. The study was undertaken in two units, each located in
      an Australian public teaching hospital. Participants included registered nurses
      employed in the units, and patients in their care. RESULTS: Four major themes
      were identified: communication among nurses and between older patients and
      nurses; strategies for pain management; environmental and organisational aspects
      of care; and complexities in the nature of pain. Nurses tended to use simple
      questioning with patients about the pain experienced. Despite the availability of
      'as required' opioid medication for breakthrough or incident pain, nurses often
      preferred to wait to determine if pain was relieved following administration of
      fixed-dose paracetamol. Time of day impacted on how pain was managed due to
      availability of nursing staff. It was unit policy for doctors to reduce
      medications prescribed, which often extended to analgesics, and nurses were left
      to deal with patient tensions in addressing analgesic needs. Complexities were
      associated with the nature of pain experienced, in terms of perceived level of
      tolerable pain, the simultaneous presence of chronic and acute pain, location of
      pain, and differentiation of pain from discomfort. CONCLUSIONS: This study
      demonstrated the intricacies associated with how analgesic needs are addressed in
      older patients, especially those with communication deficits, the complex nature
      of older patients' painful experiences, and the precarious balance of attempting
      to treat pain effectively while avoiding adverse effects of analgesics.

PMID- 22640778
TI  - How not to be a bioinformatician.
AB  - Although published material exists about the skills required for a successful
      bioinformatics career, strangely enough no work to date has addressed the matter
      of how to excel at not being a bioinformatician. A set of basic guidelines and a
      code of conduct is hereby presented to re-address that imbalance for fellow
      practitioners whose aim is to not to succeed in their chosen bioinformatics
      field. By scrupulously following these guidelines one can be sure to regress at a
      highly satisfactory rate.

PMID- 22640779
TI  - Down-regulation of viral replication by lentiviral-mediated expression of short
      hairpin RNAs against vesicular stomatitis virus ribonuclear complex genes.
AB  - Vesicular stomatitis virus (VSV) causes great economic impact to livestock
      industry and is a prototype for studying non-segmented negative-stranded RNA
      (NSNR) viruses. In this study, we evaluated the antiviral potential of unique
      short-hairpin RNA (shRNA) targeting genes that form the ribonuclear protein (RNP)
      complex of VSV serotype Indiana (VSIV). We used lentiviral vectors to construct
      cell lines that stably expressed one of seven shRNAs targeting the RNP genes of
      VSIV, namely nucleocapsid (N), phosphoprotein (P), or polymerase (L). We reported
      two N-shRNA sequences targeting the 5' or 3' end of N that significantly reduced
      N, P, and L viral transcripts (p<0.001), reduced viral protein expression, and
      reduced the viral particles shed in Vero cells (p<0.01). When we analyzed the
      sequence diversity in the target region of this N-shRNA from two field isolates,
      we detected a single base substitution outside the seed region. We also reported
      five other shRNA sequences targeting components of the viral RNA that
      significantly reduce N, P, and L viral transcripts (p<0.001) but failed to
      efficiently impair viral replication. The differences in the efficiency of the
      shRNAs tested were not due to mismatches within the target region in the genome
      of VSIV. Although partial silencing of viral transcripts by single shRNAs
      impaired but did not block VSIV replication, the combination of the shRNAs
      identified here into a multiple shRNA vector may result in inhibition of viral
      replication. These data contribute to ongoing development of RNAi-based
      technologies to combat viral diseases.

PMID- 22640780
TI  - Preceptors' views of assessing nursing students using a competency based
      approach.
AB  - The purpose of this study was to evaluate clinical competence assessment in BSc
      nursing registration education programmes. This research was undertaken in two
      phases and incorporated both quantitative and qualitative methodologies. In the
      first phase, two focus groups were conducted with preceptors working in general,
      mental health and intellectual disability nursing (n=16). In the second phase, a
      survey was undertaken with preceptors (n=837) in these disciplines. This paper
      reports on the focus group findings of preceptors' views and experiences of
      assessing undergraduate nursing degree students using a competency based
      approach. A semi-structured interview guide was used to focus the discussions.
      Three higher order categories that emerged included: attitudes to competencies,
      being a preceptor and competencies in practice. Competing demands in the clinical
      environment impacted on preceptors' experiences of the assessment process.
      Difficulties such as the wording of competency documentation and incorporation of
      skills into the assessment were articulated. The importance of a regional and
      national review of competency assessment systems to find a common language for
      student assessment as well as promoting greater student skill development within
      competency frameworks is recommended. These findings; highlight the importance of
      making assessments more workable within the current environment and aim to inform
      future development of competence assessment.

PMID- 22640781
TI  - [Severe neurological damage after central blockades].

PMID- 22640782
TI  - [Anterior spinal cord syndrome after epidural anaesthesia--a case report].
AB  - A brief patient history in which a patient developed a permanent anterior spinal
      cord syndrome after undergoing intra-abdominal surgery with postoperative pain
      management by epidural anaesthesia. A magnetic resonance imaging verified
      infarction and possible explanations for this development were reviewed. A
      precautionary measure is presented for future prevention.

PMID- 22640783
TI  - [Transient segmental hyperalgesia following epidural analgesia].
AB  - We present a case of transient segmental neurological reaction secondary to
      administration of local anaesthetics for epidural analgesia in a 42 year-old
      woman. An epidural catheter was introduced between thoracic intervertebral
      interspace 9 and 10. The patient received morphine, lidocaine, bupivacaine and
      ropivacaine. After 14 hours she experienced symptoms with burning intense pain,
      hyperalgesia with the upper limit just below the chest and the lower limit in the
      midfemur. The symptoms disappeared after 36 hours.

PMID- 22640784
TI  - [Patients with psoriasis have an increased risk of cardiovascular diseases].
AB  - Psoriasis is a chronic immunoinflammatory disease that affects 2-3% of the
      population and shares pathophysiologic mechanisms and risk factors with
      cardiovascular diseases. Studies have suggested psoriasis as an independent risk
      factor for cardiovascular disease and Danish guidelines on cardiovascular risk
      factor modification in patients with psoriasis and psoriatic arthritis have
      recently been published. We provide a short review of the current evidence and
      the Danish guidelines.

PMID- 22640785
TI  - [Autoimmune synaptic encephalitis is a disease entity on the rise].
AB  - The term autoimmune synaptic encephalitis (ASE) comprises encephalitides
      associated with autoantibodies against structures of the neuronal synapse. We
      review four types of ASE (anti-N-methyl-D-aspartate receptor encephalitis, anti
      alpha-amine-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor encephalitis,
      anti-gamma-aminobutyric acid receptor 1 encephalitis and anti-leucine-rich glioma
      inactivated 1 encephalitis) including their epidemiology, clinical
      characteristics and treatment.

PMID- 22640786
TI  - [Autoimmune synaptic encephalitis].
AB  - Autoimmune synaptic encephalitis (ASE) is a recently recognized disease entity.
      The early and correct diagnosis of ASE is of importance, since the prognosis
      depends on the early onset of treatment. We present two Danish case reports of
      ASE: a 15-year-old boy presenting with a severe course of N-methyl-D-aspartate
      encephalitis including persistent cognitive deficits, and a 59-year-old woman
      with coeliac disease presenting with leucine-rich glioma inactivated 1
      encephalitis including dyskinesia, epilepsy, psychiatric features and vocal tics.

PMID- 22640787
TI  - [Addison's disease causing acute abdomen].
AB  - A 15 year-old girl with three days of upper abdominal pain was admitted to
      hospital. Vital parametres were within normal limits. Blood samples and abdominal
      computed tomography were normal. As pain increased diagnostic laparoscopy was
      performed and mesenteriel lymphadenitis was found. Thorough examinations were
      performed including laparotomy. A synachtentest showed an insufficient level of
      cortisol. The patient was diagnosed with Addison's disease and responded well to
      treatment with cortisone. Symptoms of adrenal insufficiency can be vague, and it
      is important to keep the diagnosis in mind in patients with unexplained abdominal
      pain.

PMID- 22640788
TI  - [Atypical course of Budd-Chiari syndrome with hydrothorax].
AB  - Budd-Chiari syndrome is a very rare condition with an incidence and a prevalence
      of respectively 0.8 and 1.4 per million inhabitants per year. Significant large
      right-sided pleural effusion without significant ascites is well-known in portal
      hypertension and cirrhosis, where it occurs in 5-10% of the patients. Due to the
      presence of endometriosis and the dominant symptom in the form of hydrothorax up
      to 5 l per day delayed the correct diagnosis in a case with a 33 year-old woman.
      Reviews of the initially performed computed tomographies could have been made
      shortly after admission thus avoiding long time illness and hospitalization.

PMID- 22640789
TI  - [Fatal haemophagocytic lymphohistiocytosis and mononucleosis in a patient with
      colitis ulcerosa].
AB  - We report a case of Epstein-Barr virus primo infection with the development of
      lethal haemophagocytic lymphohistiocytosis (HLH) in a 22 year-old man, who was
      being treated with azathioprin for colitis ulcerosa. HLH is a rare, life
      threatening disease, which is caused by an inappropriate activation of the immune
      system with haemophagocytosis and multiorgan system dysfunction. Early initiation
      of treatment significantly improves survival.

PMID- 22640790
TI  - [A new genetic diagnosis of familiar gastrointestinal stromal tumour].
AB  - Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours
      of the gastrointestinal tract. Familial GIST with autosomal dominant inheritance
      and mutation in c-KIT or PDGFR-alpha, are rare and characterized by multiple
      GIST, relatively young age at diagnosis and hyperplasia of the interstitial cells
      of Cajal. Around twenty families with germ line mutations in c-KIT and three
      families with mutations in PDGFR-alpha have previously been published. In this
      case we present a family with familial GIST and mutation in c-KIT.

PMID- 22640791
TI  - [Menorrhagia as a consequence of atypical polypoid adenomyoma in uterus].
AB  - Atypical polypoid adenomyoma (APA) is an uncommon lesion of the uterus. APA is
      seen in perimenopausal women who have abnormal vaginal bleeding. We present a
      case of an APA, which in histological findings showed complex and atypical glands
      that could be confused with well-differentiated adenocarcinoma. The fact that it
      is a polypoid structure arising in the lower segment of uterus in younger women
      is helpful in diagnosing. The distinction between APA and a malignant condition
      is of high importance to treatment and prognosis.

PMID- 22640792
TI  - [Course of mole pregnancy complicated by ovarian hyperstimulation syndrome].
AB  - Ovarian hyperstimulation syndrome (OHSS) is usually an iatrogenic condition
      caused by ovulation induction. Spontaneous OHSS is rare. We present a case of
      OHSS after dilatation and curettage of a triploid partial mole. In the case
      symptoms of OHSS developed after the abortion when serum human chorionic
      gonadotropin values were declining. Noticeable was also an affected androgen
      metabolism and a high level of cancer antigen-125. It is important to be aware of
      the OHSS diagnosis in order to avoid unnecessary surgery due to suspected ovarian
      malignancy. The treatment of OHSS is supportive with intravenous fluid and
      thrombosis prophylaxis.

PMID- 22640793
TI  - [Successful conservative treatment after accidental stab wound to the chest].
AB  - A five year-old girl was admitted to hospital following an accidental stab wound
      to the chest, inflicted by a knife placed in a dishwasher's cutlery tray.
      Investigations revealed a traumatic ventricular septum defect of the heart, with
      a pericardial effusion. Since the patient remained haemodynamically stable,
      surgical intervention was considered unnecessary. At the first follow-up, an
      echocardiogram showed no visible pericardial effusion. At ten month follow-up,
      she showed initial symptoms of cardiac failure, and a renewed echocardiogram
      revealed a new pericardial effusion. It is important to perform long-term follow
      up on patients with traumatic chest wounds.

PMID- 22640794
TI  - [Measuring pH in pleural fluid is valuable when identifying the cause of purulent
      pleural effusion].
AB  - A 79 year-old woman with disseminated ovarian cancer and recurring pleural
      effusions, had thoracocentesis performed with drainage of purulent pleural fluid
      (plf) after preceding symptoms of pneumonia. Pleural empyema was suspected.
      However, a plf-pH-measurement of 7.3 made this diagnose less likely. A subsequent
      analysis of plf revealed an elevated plf-triglyceride concentration, thus
      confirming chylothorax. In order to distinguish between pleural empyema and
      chylothorax plf-pH should be considered as a routine analysis in patients with
      underlying malignancy and drainage of purulent pleural fluid.

PMID- 22640795
TI  - [Aplasia Cutis Congenita].

PMID- 22640796
TI  - Clinicopathologic correlations of renal microthrombosis and inflammatory markers
      in proliferative lupus nephritis.
AB  - INTRODUCTION: Microthrombosis is often observed in lupus nephritis (LN) lesions,
      but its clinical significance is unknown. We evaluated the clinicopathologic
      correlations of renal microthrombosis and inflammatory markers in LN. METHODS:
      Kidney biopsies from 58 patients with systemic lupus erythematosus (SLE)
      proliferative nephritis were analyzed with immunohistochemistry (IHC) for
      intravascular platelet aggregates (CD61), macrophagic infiltration (CD68), and
      activated complement deposition (C4d). Clinical data at the time of kidney biopsy
      and follow-up were analyzed with regard to pathologic IHC data. RESULTS:
      Microthrombosis was present in 52% of the tissues. It was significantly more
      prevalent in patients with antiphospholipid antibodies (aPLs) (62% versus 42%).
      The presence of microthrombosis significantly correlated with higher macrophagic
      infiltration. Macrophagic infiltration but not microthrombosis was significantly
      correlated with C4d deposition. Only macrophagic infiltration showed a
      correlation with SLE and renal activity (proteinuria and active sediment),
      whereas neither the presence of CD61+ microthrombi nor the extent of C4d
      deposition correlated with LN severity or outcome. CONCLUSIONS: Microthrombosis
      is associated with higher macrophagic infiltration in LN but does not seem to
      increase independently the severity of renal damage. Macrophagic infiltration was
      the best marker of SLE and renal activity in this LN series.

PMID- 22640798
TI  - Bayesian Variable Selection to identify QTL affecting a simulated quantitative
      trait.
AB  - BACKGROUND: Recent developments in genetic technology and methodology enable
      accurate detection of QTL and estimation of breeding values, even in individuals
      without phenotypes. The QTL-MAS workshop offers the opportunity to test different
      methods to perform a genome-wide association study on simulated data with a QTL
      structure that is unknown beforehand. The simulated data contained 3,220
      individuals: 20 sires and 200 dams with 3,000 offspring. All individuals were
      genotyped, though only 2,000 offspring were phenotyped for a quantitative trait.
      QTL affecting the simulated quantitative trait were identified and breeding
      values of individuals without phenotypes were estimated using Bayesian Variable
      Selection, a multi-locus SNP model in association studies. RESULTS: Estimated
      heritability of the simulated quantitative trait was 0.30 (SD = 0.02). Mean
      posterior probability of SNP modelled having a large effect (p ^i) was 0.0066
      (95%HPDR: 0.0014-0.0132). Mean posterior probability of variance of second
      distribution was 0.409 (95%HPDR: 0.286-0.589). The genome-wide association
      analysis resulted in 14 significant and 43 putative SNP, comprising 7 significant
      QTL on chromosome 1, 2 and 3 and putative QTL on all chromosomes. Assigning
      single or multiple QTL to significant SNP was not obvious, especially for SNP in
      the same region that were more or less in LD. Correlation between the simulated
      and estimated breeding values of 1,000 offspring without phenotypes was 0.91.
      CONCLUSIONS: Bayesian Variable Selection using thousands of SNP was successfully
      applied to genome-wide association analysis of a simulated dataset with unknown
      QTL structure. Simulated QTL with Mendelian inheritance were accurately
      identified, while imprinted and epistatic QTL were only putatively detected. The
      correlation between simulated and estimated breeding values of offspring without
      phenotypes was high.

PMID- 22640799
TI  - Non-linear response of cells to signals leads to revised characteristics of
      bystander effects inferred from their modelling.
AB  - PURPOSE: To analyze the response of naive cells to bystander signals, thus
      complementing previous studies on signal emission by irradiated cells and
      improving quantitative understanding of bystander effects. MATERIALS AND METHODS:
      Published data on reduced clonogenic survival and mutation induction in bystander
      experiments with undiluted and diluted irradiated cell-conditioned medium were
      analyzed using linear and non-linear response functions. RESULTS: The data
      indicated a highly non-linear response of cells to bystander signals. It can be
      described with sigmoid response functions, involving only a single additional
      parameter compared to the linear response assumed in existing models. Accounting
      for this non-linearity significantly modifies bystander characteristics inferred
      from the modelling, such as signal lifetime or dose dependence of signal release.
      Some signal release models are even ruled out. CONCLUSIONS: The sigmoid response
      to signals reflects complex intracellular pathways triggered and, together with
      the non-linear release of signals, supports the involvement of cytokines and/or
      reactive oxygen species in bystander effects. Further research combining
      experimental and modelling approaches is needed to elucidate the mechanisms of
      intercellular communication and their modifications by radiation, in particular
      to determine the nature of bystander signals, dynamics of their release after
      irradiation, and cellular responses to these signals.

PMID- 22640797
TI  - Clinical guidelines for the management of craniofacial fibrous dysplasia.
AB  - Fibrous dysplasia (FD) is a non-malignant condition caused by post-zygotic,
      activating mutations of the GNAS gene that results in inhibition of the
      differentiation and proliferation of bone-forming stromal cells and leads to the
      replacement of normal bone and marrow by fibrous tissue and woven bone. The
      phenotype is variable and may be isolated to a single skeletal site or multiple
      sites and sometimes is associated with extraskeletal manifestations in the skin
      and/or endocrine organs (McCune-Albright syndrome). The clinical behavior and
      progression of FD may also vary, thereby making the management of this condition
      difficult with few established clinical guidelines. This paper provides a
      clinically-focused comprehensive description of craniofacial FD, its natural
      progression, the components of the diagnostic evaluation and the multi
      disciplinary management, and considerations for future research.

PMID- 22640800
TI  - Increased toxicity of a trinuclear Pt-compound in a human squamous carcinoma cell
      line by polyamine depletion.
AB  - BACKGROUND: Mononuclear platinum anticancer agents hold a pivotal place in the
      treatment of many forms of cancers, however, there is a potential to improve
      response to evade resistance development and toxic side effects. BBR3464 is a
      promising trinuclear platinum anticancer agent, which is a polyamine mimic. The
      aim was to investigate the influence of polyamine pool reduction on the cytotoxic
      effects of the trinuclear platinum complex BBR3464 and cisplatin. Polyamine pool
      reduction was achieved by treating cells with either the polyamine biosynthesis
      inhibitor alpha-difluoromethylornithine (DFMO) or the polyamine analogue N1,N11
      diethylnorspermine (DENSPM). METHODS: A human squamous cell carcinoma cell line,
      LU-HNSCC-4, established from a primary head and neck tumour was used to evaluate
      cellular effects of each drug alone or combinations thereof. High-performance
      liquid-chromatography was used to quantify intracellular polyamine contents.
      Inductively coupled mass spectroscopy was used to quantify intracellular platinum
      uptake. Cells were exposed to DFMO or DENSPM during 48 h at concentrations
      ranging from 0 to 5 mM or 0 to 10 MUM, respectively. Thereafter, non-treated and
      treated cells were exposed to cisplatin or BBR3464 during 1 h at concentrations
      ranging from 0 to 100 MUM. A 96-well assay was used to determine cytotoxicity
      after five days after treatment. RESULTS: The cytotoxic effect of BBR3464 on LU
      HNSCC-4 cells was increased after cells were pre-treated with DENSPM or DFMO, and
      the interaction was found to be synergistic. In contrast, the interaction between
      cisplatin and DFMO or DENSPM was near-additive to antagonistic. The intracellular
      levels of the polyamines putrescine and spermidine were decreased after treatment
      with DFMO, and treatment with DENSPM resulted in an increase in putrescine level
      and concomitant decrease in spermidine and spermine levels. The uptake of BBR3464
      was significantly increased after pre-treatment of the cells with DFMO, and
      varied dependent on the concentration of DENSPM. The uptake of cisplatin was
      unchanged. CONCLUSIONS: Taken together, these results demonstrate that
      combinations of polyamine synthesis inhibitors with BBR3464 appear to be a
      promising approach to enhance the anticancer activity against HSCC.

PMID- 22640801
TI  - Assessment of the aerobic preparation and bottom ash addition as pretreatment
      steps before landfilling: impact on methanogenesis kinetics and leachate
      parameters.
AB  - This work focuses on assessing the impact of two types of waste pretreatment:
      addition of bottom ashes and aerobic pretreatment on both the onset and kinetics
      of methanogenesis and the evolution of different parameters in the leachate. It
      also studies the correlation between methane production and the different
      parameters measured in the leachate produced. A total of six 68-L pilots were
      thus used with fresh municipal solid waste (MSW) shredded to a 40-mm size. After
      14 months of landfilling, the control has produced less than 10 NLkg(-1)DM, which
      corresponds to around 7% of its biochemical methane potential (BMP).
      Nevertheless, on one hand for aerobically pretreated waste, the lag phase before
      the onset of methanogenesis is significantly reduced to 0.9 month compared to
      more than 1 year for the control. In addition to that, on average 110 NLkg(-1)DM
      (90% of the BMP) is produced within around 6.5 months. On the other hand, the
      waste with added bottom ash shows a slight improvement of the lag phase over the
      control for one of the duplicate: 6.1 months of lag phase. At this stage, on
      average of 26 NLkg(-1)DM waste are detected (22% of the BMP) no final conclusion
      concerning the impact of bottom ashes could be made. The data obtained for the
      leachate parameters agrees with the observations on methane production.
      Statistical correlation study shows that the two components of the corrected PCA
      interpret 76% of the variability of the data: SUVA (specific UV absorbance at 254
      nm) and HPI(*) (% of hydrophilic compounds) are identified as interesting
      parameters for following up the biodegradation in landfill conditions.

PMID- 22640802
TI  - Part 1: The role of waste data in building knowledge: the South African waste
      information system.
AB  - An empirical study was undertaken with 31 organisations submitting data to the
      South African Waste Information System (SAWIS) in order to explore the
      relationship between data and resultant waste knowledge generated through a
      process of learning. The results show that of the three constructs of knowledge
      (experience, data/information, and theory), experience has the greatest influence
      on building waste knowledge, nearly twice that of data/information and three
      times that of theory. Together the three constructs account for 54.1% of the
      variance in knowledge. Respondents from municipalities and private waste
      organisations reflect two distinct sub-groups in the data set. While the
      theoretical model remains the same for the two sub-groups, the way in which
      knowledge is constructed, and the variance in knowledge explained by the model,
      differs for the two. A mixed methods research design, combining quantitative
      statistical analysis and rich qualitative data, contributes to a comprehensive
      interpretation of the role of waste data in building knowledge in South Africa.
      While waste data has a minor influence on building knowledge, respondents
      acknowledge that waste data does have a positive impact on the way their
      organisations manage waste. However, it is not the data, but rather the resultant
      waste knowledge and raised level of awareness that causes the operational
      response. Experience is obtained predominantly through learning from others.
      Respondents in municipalities, emphasised learning from consultants, landfill
      site contractors, and colleagues in city-twinning programmes, while respondents
      in private waste companies, emphasised learning from experienced, senior
      colleagues.

PMID- 22640803
TI  - Pyrosequencing data analysis software: a useful tool for EGFR, KRAS, and BRAF
      mutation analysis.
AB  - BACKGROUND: Pyrosequencing is a new technology and can be used for mutation
      tests. However, its data analysis is a manual process and involves sophisticated
      algorithms. During this process, human errors may occur. A better way of
      analyzing pyrosequencing data is needed in clinical diagnostic laboratory.
      Computer software is potentially useful for pyrosequencing data analysis. We have
      developed such software, which is able to perform pyrosequencing mutation data
      analysis for epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene
      homolog and v-raf murine sarcoma viral oncogene homolog B1. The input data for
      analysis includes the targeted nucleotide sequence, common mutations in the
      targeted sequence, pyrosequencing dispensing order, pyrogram peak order and peak
      heights. The output includes mutation type and percentage of mutant gene in the
      specimen. RESULTS: The data from 1375 pyrosequencing test results were analyzed
      using the software in parallel with manual analysis. The software was able to
      generate correct results for all 1375 cases. CONCLUSION: The software developed
      is a useful molecular diagnostic tool for pyrosequencing mutation data analysis.
      This software can increase laboratory data analysis efficiency and reduce data
      analysis error rate. VIRTUAL SLIDES: The virtual slide(s) for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/1348911657684292.

PMID- 22640804
TI  - DNA packaging bias and differential expression of gene transfer agent genes
      within a population during production and release of the Rhodobacter capsulatus
      gene transfer agent, RcGTA.
AB  - Rhodobacter capsulatus produces a gene transfer agent (GTA) called RcGTA. RcGTA
      is a phage-like particle that packages R. capsulatus DNA and transfers it to
      other R. capsulatus cells. We quantified the relative frequency of packaging for
      each gene in the genome by hybridization of DNA from RcGTA particles to an R.
      capsulatus microarray. All genes were found within the RcGTA particles. However,
      the genes encoding the RcGTA particle were under-packaged compared with other
      regions. Gene transfer bioassays confirmed that the transfer of genes within the
      RcGTA structural cluster is reduced relative to those of other genes. Single-cell
      expression analysis, by flow cytometry analysis of cells containing RcGTA
      reporter gene fusion constructs, demonstrated that RcGTA gene expression is not
      uniform within a culture. This phenomenon was accentuated when the constructs
      were placed in a strain lacking a putative lysis gene involved in RcGTA release;
      a small subpopulation was found to be responsible for ~ 95% of RcGTA activity. We
      propose a mechanism whereby high levels of RcGTA gene transcription in the most
      active RcGTA-producing cells cause a reduction in their packaging frequency. This
      subpopulation's role in producing and releasing the RcGTA particles explains the
      lack of observed cell lysis in cultures.

PMID- 22640805
TI  - Shared gene expression alterations in prostate cancer and histologically benign
      prostate from patients with prostate cancer.
AB  - Prostate cancer (PCa) field effect alterations provide important clues regarding
      the initiation of these tumors and suggest targets for prevention or biomarkers
      for early detection. However, biomarkers of PCa field effects that have passed
      independent validation are lacking, largely because these alterations are subtle
      and difficult to distinguish from unrelated small changes in gene expression. We
      hypothesized that shared expression alterations in PCa and benign prostates
      containing PCa (BPCs) would have a higher potential for independent validation
      than alterations identified in BPCs alone. Expression analyses were performed on
      37 PCas and 36 unmatched BPCs and were contrasted with 28 benign prostates (BPs)
      from patients free of PCa. Most of the protein-coding genes and nonexonic RNAs
      selected according to the hypothesis were validated by quantitative RT-PCR in an
      independent set of 51 BPCs and BPs. A statistical model based on two markers
      distinguished BPCs from BPs in the RT-PCR set and in an external microarray (area
      under the curve = 0.84 and 0.90, respectively). In addition, genes with
      predominant expression in stroma were identified by expression profiling of pure
      stroma and epithelial cells. Pathway analysis identified dysregulated platelet
      derived growth factor receptor signaling in BPC stroma. These results validate
      our approach for finding PCa field effect alterations and demonstrate a PCa
      transcriptome fingerprint in nonneoplastic cells in prostates containing cancer.

PMID- 22640806
TI  - Neuronal gp130 expression is crucial to prevent neuronal loss, hyperinflammation,
      and lethal course of murine Toxoplasma encephalitis.
AB  - The obligate intracellular parasite Toxoplasma gondii infects and persists within
      neurons of approximately one-third of the human population. Intracerebral control
      of T. gondii largely depends on interferon (IFN)-gamma-producing T cells, which
      induce antiparasitic effector mechanisms in infected cells, as well as
      immunosuppressive cytokines, which prevent immunopathology. To gain further
      insight into the role of neurons in Toxoplasma encephalitis (TE), we generated
      C57BL/6 synapsin-I (Syn)-Cre gp130(fl/fl) mice, which lack gp130, the signal
      transducing receptor for the IL-6 family of cytokines, in their neurons. On
      infection with T. gondii, Syn-Cre gp130(fl/fl) mice failed to control T. gondii
      infection and died of necrotizing TE before day 77. In contrast, gp130(fl/fl)
      control mice efficiently restricted parasite replication and survived the
      infection. TE in Syn-Cre gp130(fl/fl) mice was characterized by a
      hyperinflammatory immune response with increased numbers of IL-17- and IFN-gamma
      producing CD4 and CD8 T cells but reduced intracerebral production of
      immunosuppressive transforming growth factor (TGF)-beta and IL-27. Additional in
      vitro experiments found that IL-6 stimulation of neurons induced gp130-dependent
      TGF-beta1, TGF-beta2, and IL-27 production. Importantly, gp130 expression and
      stimulation with IL-6 cytokine family members also reduced death and apoptosis of
      infected cultured neurons. Correspondingly, TE in Syn-Cre gp130(fl/fl) but not
      gp130(fl/fl) mice was characterized by progressive neuronal loss. Collectively,
      these findings indicate a crucial protective function of gp130-expressing neurons
      in a model of chronic encephalitis.

PMID- 22640807
TI  - Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and
      therapeutic strategies.
AB  - Th17 cells that secrete the cytokines IL-17A and IL-17F and express lineage
      specific transcription factor RORC (RORgammat in mice) represent a distinct
      lineage of CD4(+) T cells. Transforming growth factor-beta and inflammatory
      cytokines, such as IL-6, IL-21, IL-1beta, and IL-23, play central roles in the
      generation of Th17 cells. Th17 cells are critical for the clearance of
      extracellular pathogens, including Candida and Klebsiella. However, under certain
      conditions, these cells and their effector molecules, such as IL-17, IL-21, IL
      22, GM-CSF, and CCL20, are associated with the pathogenesis of several autoimmune
      and inflammatory diseases, such as rheumatoid arthritis, systemic lupus
      erythematosus, multiple sclerosis, psoriasis, inflammatory bowel disease, and
      allergy and asthma. This review discusses these disease states and the various
      therapeutic strategies under investigation to target Th17 cells, which include
      blocking the differentiation and amplification of Th17 cells, inhibiting or
      neutralizing the cytokines of Th17 cells, and suppressing the transcription
      factors specific for Th17 cells.

PMID- 22640808
TI  - Bone marrow ablation demonstrates that excess endogenous parathyroid hormone
      plays distinct roles in trabecular and cortical bone.
AB  - Mice null for Cyp27b1, which encodes the 25-hydroxyvitamin D-1alpha-hydroxylase
      [1alpha(OH)ase(-/-) mice], lack 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and have
      hypocalcemia and high parathyroid hormone (PTH) secretion. Intermittent,
      exogenous PTH is anabolic for bone. To determine the effect of the chronic excess
      endogenous PTH on osteogenesis and bone turnover, bone marrow ablations (BMX)
      were performed in tibiae and femurs of 6-week-old 1alpha(OH)ase(-/-) mice and in
      wild-type (WT) controls. Newly formed bone tissue was analyzed at 1, 2, and 3
      weeks after BMX. BMX did not alter the higher levels of PTH in 1alpha(OH)ase(-/-)
      mice. In the marrow cavity, trabecular volume, osteoblast number, alkaline
      phosphatase-positive areas, type I collagen-positive areas, bone formation
      related genes, and protein expression levels all increased significantly after
      BMX in 1alpha(OH)ase(-/-) mice, compared with WT. Osteoclast numbers and surface
      and ratio of RANKL/OPG-relative mRNA levels decreased significantly after BMX in
      1alpha(OH)ase(-/-) mice, compared with WT. In the cortex, alkaline phosphatase
      positive osteoblasts and osteoclast numbers increased significantly after BMX in
      1alpha(OH)ase(-/-) mice, compared with WT. These results demonstrate that chronic
      excess endogenous PTH exerts an anabolic role in trabecular bone by stimulating
      osteogenic cells and reducing bone resorption, but plays a catabolic role in
      cortical bone by enhancing bone turnover with an increase in resorption.

PMID- 22640809
TI  - Single dose exposure of sarin and physostigmine differentially regulates
      expression of choline acetyltransferase and vesicular acetylcholine transporter
      in rat brain.
AB  - Choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT)
      are the key components of cholinergic system apart from acetylcholinesterase.
      Effects of subcutaneous exposures of 0.25 and 0.5 LD(50) sarin and 0.75 mg/kg
      physostigmine on immunoreactivity levels of these two proteins (ChAT and VAChT)
      were studied. Immunoreactivity levels of ChAT decreased significantly after 1 and
      3 days in cortex and 3 days of 0.25 LD(50) sarin administration in cerebellum.
      While 0.5 LD(50) sarin exposure caused significant down regulation after 2.5 h to
      7 days in cortex and 1 and 3 days in cerebellum with respect to controls.
      Physostigmine at 0.75 mg/kg dose showed enhanced levels of ChAT after 1 day which
      decreased significantly after 3 and 7 days both in cortex and cerebellum compared
      to controls. VAChT level decreased significantly after 1 day in cortex and 3 and
      7 days in cerebellum after 0.25 LD(50) sarin administration, while 0.5 LD(50)
      sarin significantly lowered VAChT immunoreactivity level after 2.5 h and 7 days
      in cortex and 2.5 h and 1 day in cerebellum. Physostigmine at 0.75 mg/kg dose
      showed significant enhanced immunoreactivity levels of VAChT after 1, 3, and 7
      days in cortex and 3 days in cerebellum. Results show that acetylcholinesterase
      inhibition by sarin caused reduction in cholinergic neurotransmission at
      cholinergic proteins expression levels, while physostigmine caused differential
      expression of key cholinergic proteins. Moreover, cortex, which receives greater
      cholinergic innervations, is more susceptible to anticholinesterase effect on
      cholinergic gene expression. These changes can explain delayed neurocognitive
      changes during anticholinesterases induced chronic neurotoxicity.

PMID- 22640810
TI  - Association of zinc ion release and oxidative stress induced by intratracheal
      instillation of ZnO nanoparticles to rat lung.
AB  - Zinc oxide (ZnO) nanoparticles are one of the important industrial nanoparticles.
      The production of ZnO nanoparticles is increasing every year. On the other hand,
      it is known that ZnO nanoparticles have strong cytotoxicity. In vitro studies
      using culture cells revealed that ZnO nanoparticles induce severe oxidative
      stress. However, the in vivo influence of ZnO nanoparticles is still unclear. In
      the present study, rat lung was exposed to ZnO nanoparticles by intratracheal
      instillation, and the influences of ZnO nanoparticles to the lung in the acute
      phase, particularly oxidative stress, were examined. Additionally, in vitro
      cellular influences of ZnO nanoparticles were examined using lung carcinoma A549
      cells and compared to in vivo examinations. The ZnO nanoparticles used in this
      study released zinc ion in both dispersions. In the in vivo examinations, ZnO
      dispersion induced strong oxidative stress in the lung in the acute phase. The
      oxidative stress induced by the ZnO nanoparticles was stronger than that of a
      ZnCl(2) solution. Intratracheal instillation of ZnO nanoparticles induced an
      increase of lipid peroxide, HO-1 and alpha-tocopherol in the lung. The ZnO
      nanoparticles also induced strong oxidative stress and cell death in culture
      cells. Intracellular zinc level and reactive oxygen species were increased. These
      results suggest that ZnO nanoparticles induce oxidative stress in the lung in the
      acute phase. Intracellular ROS level had a high correlation with intracellular
      Zn(2+) level. ZnO nanoparticles will stay in the lung and continually release
      zinc ion, and thus stronger oxidative stress is induced.

PMID- 22640811
TI  - Definition of metabolism-dependent xenobiotic toxicity with co-cultures of human
      hepatocytes and mouse 3T3 fibroblasts in the novel integrated discrete multiple
      organ co-culture (IdMOC) experimental system: results with model toxicants
      aflatoxin B1, cyclophosphamide and tamoxifen.
AB  - The integrated discrete multiple organ co-culture system (IdMOC) allows the co
      culturing of multiple cell types as physically separated cells interconnected by
      a common overlying medium. We report here the application of IdMOC with two cell
      types: the metabolically competent primary human hepatocytes, and a metabolically
      incompetent cell line, mouse 3T3 fibroblasts, in the definition of the role of
      hepatic metabolism on the cytotoxicity of three model toxicants: cyclophosphamide
      (CPA), aflatoxin B1 (AFB) and tamoxifen (TMX). The presence of hepatic metabolism
      in IdMOC with human hepatocytes was demonstrated by the metabolism of the P450
      isoform 3A4 substrate, luciferin-IPA. The three model toxicants showed three
      distinct patterns of cytotoxic profile: TMX was cytotoxic to 3T3 cells in the
      absence of hepatocytes, with slightly lower cytotoxicity towards both 3T3 cells
      and hepatocytes in the IdMOC. AFB was selective toxic towards the human
      hepatocytes and relatively noncytotoxic towards 3T3 cells both in the presence
      and absence of the hepatocytes. CPA cytotoxicity to the 3T3 cells was found to be
      significantly enhanced by the presence of the hepatocytes, with the cytotoxicity
      dependent of the number of hepatocytes, and with the cytotoxicity attenuated by
      the presence of a non-specific P450 inhibitor, 1-aminobenzotriazole. We propose
      here the following classification of toxicants based on the role of hepatic
      metabolism as defined by the human hepatocyte-3T3 cell IdMOC assay: type I:
      direct-acting cytotoxicants represented by TMX as indicated by cytotoxicity in
      3T3 cells in the absence of hepatocytes; type II: metabolism-dependent
      cytotoxicity represented by AFB1 with effects localized within the site of
      metabolic activation (i. e. hepatocytes); and type III: metabolism-dependent
      cytotoxicity with metabolites that can diffuse out of the hepatocytes to cause
      toxicity in cells distal from the site of metabolism, as exemplified by CPA.

PMID- 22640812
TI  - Macaque monkeys exhibit behavioral signs of metamemory in an oculomotor working
      memory task.
AB  - The ability to monitor one's own memory processes is an important feature of
      human cognition and is referred to as metamemory. Although several human
      neuropsychological and neuroimaging studies have been conducted on metamemory,
      the neural mechanism that underlies this cognitive function is still unknown due
      to a lack of neurobiological research using nonhuman animals. In the present
      study, we trained four macaque monkeys to perform an oculomotor working memory
      task that was designed to be suitable for various neurobiological approaches to
      metamemory. In this task, the monkeys were sometimes allowed to choose to either
      take or escape from a spatial working memory test (Choice condition) and
      sometimes forced to take the test (Test condition). The difficulty of the task
      was manipulated by varying the number of distractors. We used two criteria to
      determine whether the monkeys showed metamnemonic ability: (1) there should be a
      negative correlation between memory performance in the Test condition and the
      escape rate in the Choice condition, and (2) memory performance should be better
      in the Choice condition than in the Test condition. Three of the four monkeys
      fulfilled these criteria. In addition, the response times of one of these three
      monkeys provided additional evidence that it used metamnemonic ability. These
      results suggest that the present task can be a useful tool for investigating the
      neural mechanism of metamemory in monkeys. Neurobiological research on metamemory
      using primate models is necessary to understand human cognition, and our study
      contributes to progress in this research area.

PMID- 22640813
TI  - Urocortin 2 modulates aspects of social behaviour in mice.
AB  - Urocortin 2 (UCN2), a member of the corticotropin-releasing hormone family, is
      involved in the regulation of stress-related behaviours in rodents. To determine
      its physiological function we generated mice lacking UCN2 by applying a classical
      knockout strategy. We examined hypothalamus-pituitary-adrenocortical axis
      activity, anxiety- and depression-related behaviours without finding significant
      differences between mutant and wild-type littermates. Investigating social
      abilities we observed, that male, but not female, UCN2 knockout animals showed an
      altered social behaviour. Here we report that male UCN2 null mice showed more
      passive social interactions and reduced aggressiveness in comparison to wild-type
      animals. In conclusion, UCN2 seems to modulate aggressive behaviour in male mice.
      Furthermore, our findings provide additional evidence for previously reported sex
      specific effects of UCN2.

PMID- 22640814
TI  - Involvement of neurotransmitters in the action of growth hormone-releasing
      hormone antagonist on passive avoidance learning.
AB  - The antagonist MZ-4-71 of growth hormone-releasing hormone (GH-RH) has been shown
      to suppress the secretion of GH and insulin-like growth factor-1 (IGF-1),
      suggesting that this class of analogs could be used for the therapy of disorders
      characterized by excessive GH secretion. Numerous GH-RH antagonists has been
      synthetized and shown to suppress the growth of various tumors. MZ-4-71
      facilitates the consolidation of passive avoidance learning. Beta-amyloid 25-35
      impairs the consolidation of passive avoidance learning and MZ-4-71 fully blocks
      this impairment. However, little is known about the possible mechanism of action
      of GR-RH antagonists on these actions. In the present work, the possible effects
      of different neurotransmitters on the action of MZ-4-71 were studied in the
      memory consolidation of passive avoidance behavior. The involvement of
      cholinergic, serotonergic, dopaminergic, GABA-ergic, adrenergic and opiate
      receptors was tested. Mice were pretreated with a nonselective alpha-adrenergic
      receptor antagonist, phenoxybenzamine, a beta-adrenergic receptor antagonist,
      propranolol, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide,
      a nonselective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a
      nonselective muscarinic acetylcholine receptor antagonist, atropine, a D2, D3, D4
      dopamine receptor antagonist, haloperidol, a gamma-aminobutyric acid subunit A
      (GABA-A) receptor antagonist, bicuculline, or a nonselective opioid receptor
      antagonist, naloxone. Atropine, methysergide, cyproheptadine and naloxone
      prevented the effects of MZ-4-71 on passive avoidance learning, whereas
      haloperidol, phenoxybenzamine, propranolol and bicuculline did not change the
      effects of MZ-4-71. The results demonstrate that the muscarinic acetylcholine
      receptor, the 5-HT1/5-HT2 serotonergic receptor and opioid receptors are involved
      as mediators in the action of MZ-4-71 on the consolidation of passive avoidance
      learning.

PMID- 22640815
TI  - Impact of electronegative low-density lipoprotein on angiographic coronary
      atherosclerotic burden.
AB  - OBJECTIVE: Low density lipoproteins (LDL) with an electronegative charge [LDL(-)]
      may cause endothelial injury. We assessed the association between serum LDL(-)
      levels and coronary artery disease (CAD) severity. METHODS: We prospectively
      enrolled patients with CAD angiographic evidence [stable angina (SA) or non-ST
      elevation-acute coronary syndrome (NSTE-ACS)], or with normal coronary arteries
      (NCA). Baseline LDL(-) serum levels were measured in all patients. Angiographic
      CAD extent was assessed by using the Bogaty extent index, while CAD severity by
      evaluating the presence of multi-vessel disease. RESULTS: Forty-seven patients
      (age 61 +/- 9 years, male sex 60%) were enrolled (17 SA, 15 NSTE-ACS and 15 NCA
      patients). LDL(-) levels were significantly higher in SA [21% (18-34) p = 0.0001]
      and NSTE-ACS [22% (18-28), p = 0.0001] as compared to NCA [6% (5-8)], without
      significant differences between SA and NSTE-ACS (p = 0.92). Multi-vessel disease
      patients had higher LDL(-) levels as compared to single-vessel disease patients
      (p = 0.002) but similar total LDL levels (p = 0.66). LDL(-) significantly
      correlated with extent index (r = 0.38, p = 0.03), while total LDL did not (p =
      0.24). CONCLUSION: LDL(-) serum levels are associated with CAD angiographic
      severity and extent. This exploratory analysis should prime further larger
      studies in order to assess LDL(-) proatherogenic role.

PMID- 22640816
TI  - Semantic patient information aggregation and medicinal decision support.
AB  - Although the health care sector has already been subjected to a major
      computerization effort, this effort is often limited to the implementation of
      standalone systems which do not communicate with each other. Interoperability
      problems limit health care applications from achieving their full potential. In
      this paper, we propose the use of Semantic Web technologies to solve
      interoperability problems between data providers. Through the development of
      unifying health care ontologies, data from multiple health care providers can be
      aggregated, which can then be used as input for a decision support system. This
      way, more data is taken into account than a single health care provider possesses
      in his local setting. The feasibility of our approach is demonstrated by the
      creation of an end-to-end proof of concept, focusing on Belgian health care
      providers and medicinal decision support.

PMID- 22640817
TI  - PopED: an extended, parallelized, nonlinear mixed effects models optimal design
      tool.
AB  - Several developments have facilitated the practical application and increased the
      general use of optimal design for nonlinear mixed effects models. These
      developments include new methodology for utilizing advanced pharmacometric
      models, faster optimization algorithms and user friendly software tools. In this
      paper we present the extension of the optimal design software PopED, which
      incorporates many of these recent advances into an easily useable enhanced GUI.
      Furthermore, we present new solutions to problems related to the design of
      experiments such as: faster and more robust FIM calculations and optimizations,
      optimizing over cost/utility functions and diagnostic tools and plots to evaluate
      design performance. Examples for; (i) Group size optimization and efficiency
      translation, (ii) Cost/constraint optimization, (iii) Optimizations with
      different FIM approximations and (iv) optimization with parallel computing
      demonstrate the new features in PopED and underline the potential use of this
      tool when designing experiments.

PMID- 22640818
TI  - Medical faculties educational network: multidimensional quality assessment.
AB  - Today, World Wide Web technology provides many opportunities in the disclosure of
      electronic learning and teaching content. The MEFANET project (MEdical FAculties
      NETwork) has initiated international, effective and open cooperation among all
      Czech and Slovak medical faculties in the medical education fields. This paper
      introduces the original MEFANET educational web portal platform. Its main aim is
      to present the unique collaborative environment, which combines the sharing of
      electronic educational resources with the use tools for their quality evaluation.
      It is in fact a complex e-publishing system, which consists of ten standalone
      portal instances and one central gateway. The fundamental principles of the
      developed system and used technologies are reported here, as well as procedures
      of a new multidimensional quality assessment.

PMID- 22640819
TI  - Modulation of anticipatory postural activity for multiple conditions of a whole
      body pointing task.
AB  - This is a study on associated postural activities during the anticipatory
      segments of a multijoint movement. Several previous studies have shown that they
      are task dependant. The previous studies, however, have mostly been limited in
      demonstrating the presence of modulation for one task condition, that is, one
      aspect such as the distance of the target or the direction of reaching. Real-life
      activities like whole-body pointing, however, can vary in several ways. How
      specific is the adaptation of the postural activities for the diverse
      possibilities of a whole-body pointing task? We used a classification paradigm to
      answer this question. We examined the anticipatory postural electromyograms for
      four different types of whole-body pointing tasks. The presence of task-dependent
      modulations in these signals was probed by performing four-way classification
      tests using a support vector machine (SVM). The SVM was able to achieve
      significantly higher than chance performance in correctly predicting the
      movements at hand (Chance performance 25%). Using only anticipatory postural
      muscle activity, the correct movement at hand was predicted with a mean rate of
      62%. Because this is 37% above chance performance, it suggests the presence of
      postural modulation for diverse conditions. The anticipatory activities consisted
      of both activations and deactivations. Movement prediction with the use of the
      activating muscles was significantly better than that obtained with the
      deactivating muscles. This suggests that more specific modulations for the
      movement at hand take place through activation, whereas the deactivation is more
      general. The study introduces a new method for investigating adaptations in motor
      control. It also sheds new light on the quantity and quality of information
      available in the feedforward segments of a voluntary multijoint motor activity.

PMID- 22640820
TI  - Scaffolder - software for manual genome scaffolding.
AB  - BACKGROUND: The assembly of next-generation short-read sequencing data can result
      in a fragmented non-contiguous set of genomic sequences. Therefore a common step
      in a genome project is to join neighbouring sequence regions together and fill
      gaps. This scaffolding step is non-trivial and requires manually editing large
      blocks of nucleotide sequence. Joining these sequences together also hides the
      source of each region in the final genome sequence. Taken together these
      considerations may make reproducing or editing an existing genome scaffold
      difficult. METHODS: The software outlined here, "Scaffolder," is implemented in
      the Ruby programming language and can be installed via the RubyGems software
      management system. Genome scaffolds are defined using YAML - a data format which
      is both human and machine-readable. Command line binaries and extensive
      documentation are available. RESULTS: This software allows a genome build to be
      defined in terms of the constituent sequences using a relatively simple syntax.
      This syntax further allows unknown regions to be specified and additional
      sequence to be used to fill known gaps in the scaffold. Defining the genome
      construction in a file makes the scaffolding process reproducible and easier to
      edit compared with large FASTA nucleotide sequences. CONCLUSIONS: Scaffolder is
      easy-to-use genome scaffolding software which promotes reproducibility and
      continuous development in a genome project. Scaffolder can be found at
      http://next.gs.

PMID- 22640821
TI  - Rejection of pharmaceuticals by forward osmosis membranes.
AB  - Rejection of four pharmaceutical compounds, carbamazepine, diclofenac, ibuprofen
      and naproxen, by forward osmosis (FO) membranes was investigated in this study.
      For the first time, the rejection efficiency of the pharmaceutical compounds was
      compared between commercial cellulose triacetate (CTA) based membranes and thin
      film composite (TFC) polyamide based membranes. The rejection behavior was
      related to membrane interfacial properties, physicochemical characteristics of
      the pharmaceutical molecules and feed solution pH. TFC polyamide membranes
      exhibited excellent overall performance, with high water flux, excellent pH
      stability and great rejection of all pharmaceuticals investigated (>94%). For
      commercial CTA based FO membranes, hydrophobic interaction between the compounds
      and membranes exhibited strong influence on their rejection under acidic
      conditions. The pharmaceuticals rejection was well correlated to their
      hydrophobicity (log D). Under alkaline conditions, both electrostatic repulsion
      and size exclusion contributed to the removal of deprotonated molecules. The
      pharmaceuticals rejection by CTA-HW membrane at pH 8 followed the order:
      diclofenac (99%)>carbamazepine (95%)>ibuprofen (93%) ~ naproxen (93%). These
      results can be important for FO membrane synthesis, modification and their
      application in water purification.

PMID- 22640822
TI  - Occurrence and analysis of parabens in municipal sewage sludge from wastewater
      treatment plants in Madrid (Spain).
AB  - A rapid method for determination of seven parabens and two chlorinated by
      products in sewage sludge was developed based on matrix solid-phase dispersion
      and gas chromatography-tandem mass spectrometry. The analytical procedure showed
      good recoveries that ranged from 80 to 125%, with relative standard deviations
      lower than 12% and low detection limits, ranging from 0.1 to 2.0 ng g(-1) dry
      weight. The developed method was applied to the analysis of sewage sludge
      collected during 2010 in 19 wastewater treatment plants (WWTPs) located in
      various urban, industrial or rural zones in Madrid (Spain). Methylparaben was
      found in most of the WWTPs sampled (95%) at levels between 5.1 and 26.2 ng g(-1)
      dry weight and propylparaben was detected in 74% of the WWTPs at levels up to
      44.1 ng g(-1) dry weight. In order to study the temporal variation of parabens
      and two chlorinated parabens during a four-year period, sludge samples were
      collected from 3 selected WWTPs. The levels of methylparaben encountered were
      rather constant throughout the sampling period whereas propylparaben levels
      slightly increased. In one of the WWTPs monitored, isopropylparaben was found at
      the beginning of the sampling period but its content decreased and was not
      detected in the 2010 sampling.

PMID- 22640823
TI  - Catalytic hydrodechlorination of dioxins over palladium nanoparticles in
      supercritical CO2 swollen microcellular polymers.
AB  - In this study, palladium nanoparticles embedded in monolithic microcellular high
      density polyethylene supports are synthesized as heterogeneous catalysts for
      remediation of 1,6-dichlorodibenzo-p-dioxin and 2,8-dichlorodibenzofuran in 200
      atm of supercritical carbon dioxide containing 10 atm of hydrogen gas and at 50
      90 degrees C. Stepwise removal of chlorine atoms takes place first, followed by
      saturation of two benzene rings with slower reaction rates. The pseudo first
      order rate constant of initial hydrodechlorination for 2,8-dichlorodibenzofuran
      is 4.3 times greater than that for 1,6-dichlorodibenzo-p-dioxin at 78 degrees C.
      The catalysts are easily separated from products and can be recyclable and
      reusable without complicated recovery and cleaning procedures.

PMID- 22640824
TI  - Ge4+ doped TiO2 for stoichiometric degradation of warfare agents.
AB  - Germanium doped TiO(2) was prepared by homogeneous hydrolysis of aqueous
      solutions of GeCl(4) and TiOSO(4) with urea. The synthesized samples were
      characterized by X-ray diffraction, scanning electron microscopy, EDS analysis,
      specific surface area (BET) and porosity determination (BJH). Ge(4+) doping
      increases surface area and content of amorphous phase in prepared samples. These
      oxides were used in an experimental evaluation of their reactivity with chemical
      warfare agent, sulphur mustard, soman and agent VX. Ge(4+) doping worsens sulphur
      mustard degradation and improves soman and agent VX degradation. The best degree
      of removal (degradation), 100% of soman, 99% of agent VX and 95% of sulphur
      mustard, is achieved with sample with 2 wt.% of germanium.

PMID- 22640825
TI  - Alternative strategies for selecting subsets of predicting SNPs by LASSO-LARS
      procedure.
AB  - BACKGROUND: The least absolute shrinkage and selection operator (LASSO) can be
      used to predict SNP effects. This operator has the desirable feature of including
      in the model only a subset of explanatory SNPs, which can be useful both in QTL
      detection and GWS studies. LASSO solutions can be obtained by the least angle
      regression (LARS) algorithm. The big issue with this procedure is to define the
      best constraint (t), i.e. the upper bound of the sum of absolute value of the SNP
      effects which roughly corresponds to the number of SNPs to be selected. Usai et
      al. (2009) dealt with this problem by a cross-validation approach and defined t
      as the average number of selected SNPs overall replications. Nevertheless, in
      small size populations, such estimator could give underestimated values of t.
      Here we propose two alternative ways to define t and compared them with the
      "classical" one. METHODS: The first (strategy 1), was based on 1,000 cross
      validations carried out by randomly splitting the reference population (2,000
      individuals with performance) into two halves. The value of t was the number of
      SNPs which occurred in more than 5% of replications. The second (strategy 2),
      which did not use cross-validations, was based on the minimization of the Cp-type
      selection criterion which depends on the number of selected SNPs and the expected
      residual variance. RESULTS: The size of the subset of selected SNPs was 46, 189
      and 64 for the classical approach, strategy 1 and 2 respectively. Classical and
      strategy 2 gave similar results and indicated quite clearly the regions were QTL
      with additive effects were located. Strategy 1 confirmed such regions and added
      further positions which gave a less clear scenario. Correlation between GEBVs
      estimated with the three strategies and TBVs in progenies without phenotypes were
      0.9237, 0.9000 and 0.9240 for classical, strategy 1 and 2 respectively.
      CONCLUSIONS: This suggests that the Cp-type selection criterion is a valid
      alternative to the cross-validations to define the best constraint for selecting
      subsets of predicting SNPs by LASSO-LARS procedure.

PMID- 22640826
TI  - The effects of serum lipids on the in vitro activity of lumefantrine and
      atovaquone against Plasmodium falciparum.
AB  - BACKGROUND: Lumefantrine and atovaquone are highly lipophilic anti-malarial
      drugs. As a consequence absorption is increased when the drugs are taken together
      with a fatty meal, but the free fraction of active drug decreases in the presence
      of triglyceride-rich plasma lipoproteins. In this study, the consequences of
      lipidaemia on anti-malarial drug efficacy were assessed in vitro. METHODS: Serum
      was obtained from non-immune volunteers under fasting conditions and after
      ingestion of a high fat meal and used in standard Plasmodium falciparum in-vitro
      susceptibility assays. Anti-malarial drugs, including lumefantrine, atovaquone
      and chloroquine in five-fold dilutions (range 0.05 ng/ml-1 ug/mL) were diluted in
      culture medium supplemented with fasting or post-prandial 10% donor serum. The in
      vitro drug susceptibility of parasite isolates was determined using the 3H
      hypoxanthine uptake inhibition method and expressed as the concentration which
      gave 50% inhibition of hypoxanthine uptake (IC50). RESULTS: Doubling plasma
      triglyceride concentrations (from 160 mg/dL to 320 mg/dL), resulted in an
      approximate doubling of the IC50 for lumefantrine (191 ng/mL to 465 ng/mL, P <
      0.01) and a 20-fold increase in the IC50 for atovaquone (0.5 ng/mL to 12 ng/ml; P
      < 0.01). In contrast, susceptibility to the hydrophilic anti-malarial chloroquine
      did not change in relation to triglyceride content of the medium. CONCLUSIONS:
      Lipidaemia reduces the anti-malarial activity of lipophilic anti-malarial drugs.
      This is an important confounder in laboratory in vitro testing and it could have
      therapeutic relevance.

PMID- 22640828
TI  - Production of low kinetic energy electrons and energetic ion pairs by
      Intermolecular Coulombic Decay.
AB  - PURPOSE: The paper gives an introduction into Interatomic and Intermolecular
      Coulombic Decay (ICD). ICD is an autoionization process, which contrary to Auger
      decay involves neighbouring sites of the initial vacancy as an integral part of
      the decay transition. As a result of ICD, slow electrons are produced which
      generally are known to be active in radiation damage. The author summarizes the
      properties of ICD and reviews a number of important experiments performed in
      recent years. MATERIALS AND METHODS: Intermolecular Coulombic Decay can generally
      take place in weakly bonded aggregates in the presence of ionizing particles or
      ionizing radiation. Examples collected here mostly use soft X-rays produced by
      synchrotron radiation to ionize, and use rare-gas clusters, water clusters or
      solutes in a liquid jet to observe ICD after irradiation. RESULTS: Intermolecular
      Coulombic Decay is initiated by single ionization into an excited state. The
      subsequent relaxation proceeds via an ultra-fast energy transfer to a
      neighbouring site, where a second ionization occurs. Secondary electrons from ICD
      have clearly been identified in numerous systems. ICD can take place after
      primary ionization, as the second step of a decay cascade which also involves
      Auger decay, or after resonant excitation with an energy which exceeds the
      ionization potential of the system. CONCLUSIONS: ICD is expected to play a role
      whenever particles or radiation with photon energies above the ionization
      energies for inner valence electrons are present in weakly bonded matter, e.g.,
      biological tissue. The process produces at the same time a slow electron and two
      charged atomic or molecular fragments, which will lead to structural changes
      around the ionized site.

PMID- 22640827
TI  - Association of cytokine and matrix metalloproteinase profiles with disease
      activity and function in ankylosing spondylitis.
AB  - INTRODUCTION: The pathology of ankylosing spondylitis (AS) suggests that certain
      cytokines and matrix metalloproteinases (MMPs) might provide useful markers of
      disease activity. Serum levels of some cytokines and MMPs have been found to be
      elevated in active disease, but there is a general lack of information about
      biomarker profiles in AS and how these are related to disease activity and
      function. The purpose of this study was to investigate whether clinical measures
      of disease activity and function in AS are associated with particular profiles of
      circulating cytokines and MMPs. METHODS: Measurement of 30 cytokines, five MMPs
      and four tissue inhibitors of metalloproteinases was carried out using Luminex(r)
      technology on a well-characterised population of AS patients (n = 157). The
      relationship between biomarker levels and measures of disease activity (Bath
      ankylosing spondylitis disease activity index (BASDAI)), function (Bath
      ankylosing spondylitis functional index) and global health (Bath ankylosing
      spondylitis global health) was investigated. Principal component analysis was
      used to reduce the large number of biomarkers to a smaller set of independent
      components, which were investigated for their association with clinical measures.
      Further analyses were carried out using hierarchical clustering, multiple
      regression or multivariate logistic regression. RESULTS: Principal component
      analysis identified eight clusters consisting of various combinations of
      cytokines and MMPs. The strongest association with the BASDAI was found with a
      component consisting of MMP-8, MMP-9, hepatocyte growth factor and CXCL8, and was
      independent of C-reactive protein levels. This component was also associated with
      current smoking. Hierarchical clustering revealed two distinct patient clusters
      that could be separated on the basis of MMP levels. The high MMP cluster was
      associated with increased C-reactive protein, the BASDAI and the Bath ankylosing
      spondylitis functional index. CONCLUSIONS: A profile consisting of high levels of
      MMP-8, MMP-9, hepatocyte growth factor and CXCL8 is associated with increased
      disease activity in AS. High MMP levels are also associated with smoking and
      worse function in AS.

PMID- 22640829
TI  - Safety results from a phase III study (TURANDOT trial by CECOG) of first-line
      bevacizumab in combination with capecitabine or paclitaxel for HER-2-negative
      locally recurrent or metastatic breast cancer.
AB  - BACKGROUND: We report safety data from a randomised, phase III study
      (CECOG/BC.1.3.005) evaluating first-line bevacizumab plus paclitaxel or
      capecitabine for locally recurrent or metastatic breast cancer. PATIENTS AND
      METHODS: Patients aged >=18 years with human epidermal growth factor receptor-2
      negative breast adenocarcinoma were randomised to Arm A: bevacizumab 10 mg/kg
      days 1 and 15; paclitaxel 90 mg/m(2) days 1, 8, and 15, every 4 weeks; or Arm B:
      bevacizumab 15 mg/kg day 1; capecitabine 1000 mg/m(2) b.i.d., days 1-14, every 3
      weeks, until disease progression, unacceptable toxicity or consent withdrawal.
      RESULTS: A post hoc interim safety analysis included 561 patients (Arm A: 284,
      Arm B: 277). The regimens demonstrated similar frequencies of all-grade and
      serious adverse events (SAEs), but different safety profiles. Treatment-related
      events occurred in 85.2% (Arm A) and 78.0% (Arm B) of patients. Fatigue was most
      common in Arm A (30.6% versus 23.5% Arm B), and hand-foot syndrome (HFS) most
      common in Arm B (49.5% versus 2.5% Arm A). Diarrhoea (Arm A: 0.4%, Arm B: 1.4%)
      and pulmonary embolism (Arm A: 0.7%, Arm B: 1.1%) were the most frequently
      reported SAEs. CONCLUSION: These findings are in-line with safety data for
      bevacizumab plus paclitaxel or capecitabine, reported in previous phase III
      trials.

PMID- 22640830
TI  - All-trans-retinoic acid inhibits growth of head and neck cancer stem cells by
      suppression of Wnt/beta-catenin pathway.
AB  - Differentiation therapy is a novel approach to eradicate cancer stem cells
      (CSCs), including head and neck squamous carcinoma CSC (HNSC CSC). All-trans
      retinoic acid (ATRA) is a potent differentiating agent. We studied the anti
      tumour effect of ATRA on HNSC CSC. HNSC CSCs were differentiated by ATRA in a
      serum-free conditioned medium. The effect of differentiation on tumour growth was
      assessed in vitro and in vivo, and chemosensitisation was examined using a
      colorimetric viability assay. In addition, the involvement of Wnt/beta-catenin
      signalling as an underlying mechanism of the anti-tumour effect of retinoic acid
      (RA) on HNSC CSCs was assessed. ATRA suppressed the expression of the stem cell
      markers Oct4, Sox2, Nestin and CD44 in HNSC CSCs and inhibited the proliferation
      of HNSC CSCs in vitro and in vivo. Furthermore, ATRA treatment augmented the
      chemosensitising effects of cisplatin. The anti-tumour effects of ATRA may be
      associated with down-regulation of Wnt/beta-catenin signalling. In conclusion,
      ATRA may be potentially valuable in treatment of HNSC CSC, especially in
      combination with cisplatin.

PMID- 22640831
TI  - Adaptation of teleosts to very high salinity.
AB  - A number of species of euryhaline teleosts have the remarkable ability to adapt
      and survive in environments of extreme salinity, up to two or even three times
      the osmolality of seawater. This review looks at some of the literature
      describing the adaptive changes that occur, primarily with intestinal water
      absorption and with the properties of the gill epithelium. While there is much
      that is still not completely understood, recent work has begun to look at these
      adaptations at the cellular and molecular level. As with seawater osmoregulation,
      fish adapting to hypersaline conditions generally increase drinking rates and
      water absorption across the intestine by solute-linked transport. This process
      requires increased activity, expression levels and possibly changes in subunit
      isoforms of Na(+)/K(+)-ATPase pumps, along with increases in other components of
      the NaCl absorptive pathway. Additionally, recent studies have demonstrated the
      importance of luminal anion exchange activity and of luminal alkalinization,
      which can support absorption against increasing osmotic gradients by promoting
      divalent ion precipitation (CaCO(3)) and by conversion of HCO(3)(-) ions to
      CO(2). The steepness of the lumen to blood osmotic gradient vis-a-vis the NaCl
      absorptive capacity, along with the accumulation of non-absorbed Mg(++) and
      SO(4)(--), likely become the limiting factors for survival in hypersaline
      conditions. Of interest is the observation of predicted hyperosmotic fluid
      absorption by the intestine in several species. Adaptive changes in the gill
      epithelium are also critical in this process, allowing for secretion of absorbed
      NaCl from the extracellular fluids. Most notably there are important changes in
      the numbers and size of mitochondrion-rich (MR) cells, the sites of active
      secretion of Cl(-), which ultimately drives the overall process of NaCl
      secretion. Balance studies of intake and output clearly indicate that a decrease
      in the osmotic permeability of the gill epithelium must also occur. The molecular
      correlates of this effect are not known, although decreased expression of one or
      more aquaporins seems to be a likely possibility. Finally, the regulatory changes
      seen with hypersaline adaptation may provide important new insights into
      epithelial function, including the role of organized transport assemblies
      ("metabolons") and changes in the expression of tight junction proteins such as
      claudins or occludins, which may modulate electrolyte permeabilities.

PMID- 22640833
TI  - Foetal/neonatal alloimmune thrombocytopenia in Egypt; human platelet antigen
      genotype frequencies and antibody detection and follow-up in pregnancies.
AB  - BACKGROUND AND OBJECTIVES: Foetal and neonatal alloimmune thrombocytopenia
      (FNAIT) is studied mainly in Caucasian populations. Severe thrombocytopenia
      (<50*10(9)/L) gives risk of haemorrhage and the most feared complication is
      intracranial haemorrhage (ICH). In Caucasian populations anti-human platelet
      antigen (HPA)-1a antibodies are the cause of FNAIT in >80% of the cases. The aims
      of this project were to study the gene frequencies of HPA-1-5 and 15 alleles in
      an Egyptian population (Arabic), and to determine the frequency of HPA-1a and -5b
      immunisations in a cohort of Egyptian pregnant women. MATERIALS AND METHODS:
      Altogether 6974 pregnant women were included in the study. Genotyping was
      performed by polymerase chain reaction and antibodies were detected by flow
      cytometry and enzyme-linked immunosorbent assay. HPA-1-5 and 15 alleles were
      studied in 367 individuals. RESULTS: The HPA genotypes differed from genotypes
      published from different Caucasian and Chinese (Han) populations in HPA-1, -2, 
      3, and -5 systems with significant higher frequency of HPA-1b, -2b and -5b. The
      rate of HPA-1a alloimmunisation was found comparable to Caucasian populations.
      Severe thrombocytopenia was found in two newborns. No bleeding complication was
      reported. Anti-HPA-5b antibodies were detected in 4.4% of the pregnant women.
      Clinical consequences of these antibodies were not studied. CONCLUSION: The HPA
      1bb and -5bb genotypes are more frequent in the Egyptian Arabic population
      studied compared to Caucasian populations. FNAIT due to anti-HPA-1a and -5b
      antibodies must be suspected in cases of neonatal thrombocytopenia. Further large
      prospective studies are needed to increase the knowledge of clinical
      complications related to HPA alloantibodies in populations with different genetic
      backgrounds.

PMID- 22640832
TI  - Mitochondrial RNA polymerase is an essential enzyme in erythrocytic stages of
      Plasmodium falciparum.
AB  - We have shown that transgenic Plasmodium falciparum parasites expressing the
      yeast DHODH (dihydroorotate dehydrogenase) are independent of the mtETC
      (mitochondrial electron transport chain), suggesting that they might not need the
      mitochondrial genome (mtDNA), since it only encodes three protein subunits
      belonging to the mtETC and fragmentary ribosomal RNA molecules. Disrupting the
      mitochondrial RNA polymerase (mtRNAP), which is critical for mtDNA replication
      and transcription, might then cause the generation of a rho(0) parasite line
      lacking mtDNA. We made multiple attempts to disrupt the mtRNAP gene by double
      crossover recombination methods in parasite lines expressing yDHODH either
      episomally or integrated in the genome, but were unable to produce the desired
      knockout. We verified that the mtRNAP gene was accessible to recombination by
      successfully integrating a triple HA tag at the 3' end via single cross-over
      recombination. These studies suggest that mtRNAP is essential even in mtETC
      independent P. falciparum parasites.

PMID- 22640834
TI  - Editorial. One-year epidemiological prospective follow-up study to detect new and
      long term AIDS infections.

PMID- 22640835
TI  - Clinical use of fresh-frozen plasma in neonatal intensive care unit.
AB  - Recommendations for FFP use in neonates are based on a very limited amount of
      data, and not on well-designed randomized controlled trials. This retrospective
      study was performed to analyze our experience with FFP use in neonatal intensive
      care unit (NICU). From January 2006 until August 2011 a total of 80 neonates were
      identified as having been treated with FFP. The most common indication for FFP
      use was prolonged PT or aPTT, representing 32.8% of all usages of FFP. Following
      FFT treatment PT and aPTT normalized in 42% and 60% patients, respectively. Our
      results suggest that FFP were often used in acceptable indications in NICU.

PMID- 22640836
TI  - Elevated baseline hs-cTnT levels predict exercise-induced myocardial ischemia in
      patients with peripheral arterial disease.
AB  - INTRODUCTION: Due to the systemic nature of atherosclerosis, the prevalence of
      coronary artery disease (CAD) is high in patients with peripheral arterial
      disease (PAD). A biochemical assay for assessing cardiac risk might improve
      clinical evaluation of PAD patients. The aim of this study was to investigate
      whether a new high-sensitivity cardiac Troponin T (hs-cTnT) assay can predict
      exercise-induced myocardial ischemia in PAD patients without clinical signs of
      CAD. METHODS: Sixty-eight ambulatory patients with Fontaine stage II PAD
      underwent treadmill stress testing to maximum walking distance. Myocardial
      ischemia was assessed using a 2-lead Holter ECG and ST-segment depression of >=
      0.2 mV was considered significant. Hs-cTnT was measured from serum samples taken
      at baseline as well as 5, 10 and 30 min after exercise. RESULTS: Hs-cTnT baseline
      levels were significantly higher (19.3 ng/L (5.0; 20.2 ng/L) vs. 6.6 ng/L (4.4;
      9.4 ng/L); p=0.037) and increase of serum levels 5 min after cessation of
      exercise was more pronounced (1.09 ng/L (0.23; 1.80 ng/L) vs. 0.22 ng/L (-0.1;
      0.65 ng/L), p=0.032) in ECG positive patients compared to individuals with normal
      ECG. Logistic regression analysis identified the baseline hs-cTnT serum level as
      an independent risk factor for developing significant exercise-induced ST-segment
      depression (odds ratio 1.2 per 1-unit increase, p=0.015). CONCLUSIONS: In
      patients with PAD, exercise-induced myocardial ischemia is associated with
      elevated baseline levels and a significant early increase of hs-cTnT serum
      levels.

PMID- 22640837
TI  - Slantingly cross loading sample system enables simultaneous performance of
      separation and mixture to detect molecular interactions on thin-layer
      chromatography.
AB  - Anthocyanins are major flower pigments that can be affected by copigments,
      colorless compounds that can modify anthocyanin coloration to more intense and
      bluer. Thin-layer chromatography (TLC) is an available technique to separate and
      analyze anthocyanins and copigments. To easily and comprehensively detect
      copigments, we added function of mixture of compounds to TLC; by slantingly cross
      loading samples on TLC, compounds are symmetrically developed at various angle
      lines from the upper origin to individual R(f) values and cross each other in an
      orderly fashion, where mixture is simultaneously performed with separation.
      Occurrence of copigments can be detected as a coloration change on the developed
      line of anthocyanin. Pink sweet pea (Lathyrus odoratus L.) petals were analyzed
      by the cross-TLC and a more intense spot and a paler spot on the anthocyanin line
      were detected. As each spot overlapped with an ultraviolet absorbance line, each
      of these ultraviolet absorption compounds was purified and identified as
      kaempferol 3-rhamnoside and 2-cyanoethyl-isoxazolin-5-one, respectively. Whereas
      kaempferol 3-rhamnoside is a flavonoid and had a general copigment effect of more
      intense and bluer coloration change, 2-cyanoethyl-isoxazolin-5-one is a compound
      whose structure is outside of conventional categories of copigments and had a
      novel effect to change anthocyanin coloration paler while maintaining color tone.
      We determined that the search for copigments should be carried out without pre
      existing prediction of structures and effects. We have shown that slantingly
      cross loading samples system on plate-type chromatography is an effective
      technique for such comprehensive analysis of molecular interaction.

PMID- 22640838
TI  - A sensitive and accurate liquid chromatography-tandem mass spectrometry method
      for quantitative determination of the novel hepatitis C NS5A inhibitor BMS-790052
      (daclastasvir) in human plasma and urine.
AB  - A liquid-liquid extraction (LLE) and liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) methods have been developed and validated for the
      quantification of BMS-790052 (daclastasvir) in human plasma and urine. The
      samples were extracted with methyl-t-butyl ether (MTBE) before analyzing by an
      API 4000 mass spectrometer which was operated in a multiple reaction monitoring
      (MRM) mode for detection of positively charged ions of BMS-790052 and its
      internal standard, 13C10-BMS-790052. The standard curves ranged from 0.050 to
      50.0 ng/mL for BMS-790052 in human plasma, and 1.00-1000 ng/mL in human urine.
      The intra-assay precision (%CV), based on four levels of analytical QCs (low,
      geometric mean, mid and high), was within 8.6%; inter-assay precision (%CV) was
      within 6.7% for both plasma and urine methods, and the mean assay accuracy (%Dev)
      was within +/-3.0% for both plasma and urine methods. The ruggedness of this
      accurate, precise, and selective LLE-LC-MS/MS method has been demonstrated in the
      successful analysis of several thousand clinical study samples.

PMID- 22640839
TI  - Sezary syndrome: a study of 176 patients at Mayo Clinic.
AB  - BACKGROUND: Sezary syndrome (SS), a leukemic variant of cutaneous T-cell
      lymphoma, is characterized by erythroderma and by atypical lymphocytes (Sezary
      cells) in peripheral blood. Although numerous studies have examined the range of
      disease in cutaneous T-cell lymphoma, a relative paucity of data exists to
      describe the long-term outcome of patients with SS. OBJECTIVE: We sought to study
      long-term survival and prognostic factors of patients with SS. METHODS: A
      retrospective chart review was conducted to identify patients with SS seen at
      Mayo Clinic from 1976 to 2010. Cox proportional hazards regression models,
      adjusted for age, were fit to evaluate factors associated with overall survival.
      RESULTS: In total, 176 patients were identified with a clinicopathologic
      diagnosis of SS. Overall survival was 86.1% and 42.3% at 1 and 5 years,
      respectively, after diagnosis (median survival, 4.0 years). After adjustment for
      age, potential predictors of worse survival included lactate dehydrogenase level
      at presentation (hazard ratio [HR] 1.71; 95% confidence interval [CI] 1.18-2.47
      per doubling), prior diagnosis of mycosis fungoides (HR 2.68; 95% CI 1.44-4.98),
      and the presence of T-cell receptor gene rearrangements in skin (HR 2.59; 95% CI
      1.38-4.87) and in blood (HR 2.05; 95% CI 1.00-4.21). LIMITATIONS: This study is
      retrospective and represents a single academic center population. CONCLUSIONS: To
      our knowledge, this research evaluated the largest population of patients with SS
      studied to date. It shows that overall survival continues to be poor, with a
      median survival of 4.0 years after diagnosis.

PMID- 22640840
TI  - Airway defense mechanisms.
AB  - A multitude of overlapping defenses has evolved to help combat the inventiveness
      of pathogens seeking to invade us, and because the lung is the most common
      primary route of infection, it is in the lung that the most varied responses are
      seen. This article focuses on recent research, particularly in innate immunity,
      and gives a general overview of the defense systems so far identified. Of
      particular interest is the markedly increased understanding of the role of small
      molecules such as defensins, cathelicidins, and collectins. Areas in which
      abnormalities may be relevant to patients with bronchiectasis are highlighted.

PMID- 22640841
TI  - Pathogenesis of bronchiectasis.
AB  - The pathogenesis of bronchiectasis cannot be explained by a single cause. The
      current model is a vicious cycle of inflammation and altered response to
      infection. This cycle depends not only on the type and virulence of the pathogen
      but also on the host immune response. In this response, too much or too little
      can damage the airways or fail to clear the pathogen, thus increasing the
      probability of further infection. This review describes the changes and
      advancement in the pathogenesis of bronchiectasis, including mechanisms of injury
      and host factors.

PMID- 22640842
TI  - The initial evaluation of adults with bronchiectasis.
AB  - Bronchiectasis can be caused by a myriad of underlying conditions or
      environmental insults to the bronchial tree. Despite a detailed evaluation, the
      cause remains undetermined in approximately 50% of cases. Nonetheless, it is
      important to use a systematic approach to the diagnostic evaluation of a patient
      with newly diagnosed bronchiectasis, because a substantial proportion of patients
      have a specific underlying diagnosis with implications for prognosis or
      treatment. There is not one panel of tests that can be recommended for all
      patients. This article reviews the initial evaluation of an adult patient with
      bronchiectasis.

PMID- 22640844
TI  - Genetic causes of bronchiectasis.
AB  - Our understanding of the pathologic cycle leading to the development of
      bronchiectasis is enhanced by greater understanding of the genetic influences
      contributing to its development. Genome-wide linkage analysis, family-based
      genetic linkage studies, and the testing of candidate genes have all greatly
      advanced our understanding of the complexity of the genetic basis of
      bronchiectasis. This article discusses how allelic variations, gene modifiers,
      HLA associations, and the interplay of developmental, host, and environmental
      factors all contribute in lesser and greater degrees, depending on the specific
      disease, toward the development of bronchiectasis in a spectrum of disease
      processes.

PMID- 22640843
TI  - Imaging of bronchiectasis.
AB  - Despite limitations, high-resolution computed tomography (HRCT) continues to be
      the gold standard for establishing the anatomic extent and severity of
      bronchiectasis. HRCT allows insight into the physiologic consequences of
      bronchiectasis. Recent reports show that there is good correlation between
      measurements of the density of airway walls and airway obstruction in patients
      with chronic obstructive pulmonary disease. Measuring peak airway wall density
      may prove of value for assessing the severity of bronchiectasis as well as
      potentially serving as a biomarker for measuring response to therapy. The full
      potential of computed tomography for evaluating airways disease has yet to be
      fully explored.

PMID- 22640845
TI  - Allergic bronchopulmonary aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is caused by an exaggerated T(H)2
      response to the ubiquitous mold Aspergillus fumigatus. ABPA develops in a small
      fraction of patients with cystic fibrosis and asthma, suggesting that intrinsic
      host defects play a major role in disease susceptibility. This article reviews
      current understanding of the immunopathology, clinical and laboratory findings,
      and diagnosis and management of ABPA. It highlights clinical and laboratory clues
      to differentiate ABPA from cystic fibrosis and asthma, which are challenging
      given clinical and serologic similarities. A practical diagnostic algorithm and
      management scheme to aid in the treatment of these patients is outlined.

PMID- 22640846
TI  - Bronchiectasis and nontuberculous mycobacterial disease.
AB  - Over the last 30 years it has become increasingly clear that nontuberculous
      mycobacterial (NTM) lung infections and bronchiectasis are closely related
      disorders. Although incontrovertible proof is lacking, there is a growing
      consensus of opinion that NTM lung disease characterized by nodules and
      bronchiectasis (nodular/bronchiectatic NTM lung disease) may be a consequence of
      preexisting bronchiectasis that predisposes to NTM infection and disease. To use
      published diagnostic guidelines effectively, physicians must become familiar with
      the disease-causing potential of individual NTM species. Essentially all NTM
      patients have bronchiectasis, so optimal overall patient management requires
      successful therapeutic strategies for both NTM infection and bronchiectasis.

PMID- 22640847
TI  - Diffuse panbronchiolitis.
AB  - Diffuse panbronchiolitis (DPB) is characterized by chronic airway infection with
      diffuse bilateral micronodular pulmonary lesions. DPB is mainly distributed in
      east Asian people. Studies on causes of the disease point to a genetic
      predisposition unique to Asians. The advent of low-dose, long-term macrolide
      therapy has changed disease prognosis. The mechanism of action is attributed to
      anti-inflammatory actions of 14-membered and 15-membered ring macrolides.
      Recently, the success of macrolide therapy in DPB has extended its application to
      the treatment of other chronic airway inflammatory diseases.

PMID- 22640848
TI  - Recent advances in cystic fibrosis.
AB  - Cystic fibrosis (CF) is an inherited chronic disease that remains a common cause
      of morbidity and mortality in affected patients, mostly in the young. A wealth of
      knowledge has been gained into the genetics, pathophysiology, and clinical
      manifestation of the disease. In parallel with these new insights into the
      disease, novel treatments have been developed or are under development that have
      had a major impact on quality of life and survival. Improvement in the delivery
      of care to patients in CF centers, using a team-based approach, and constant
      review of process, and by quality improvement projects, have also had an impact
      on outcomes in CF.

PMID- 22640849
TI  - Evaluating success of therapy for bronchiectasis: what end points to use?
AB  - Long-term treatment goals of bronchiectasis frequently include limiting the
      bacterial burden and inflammatory insult in the airways with the aim of improving
      symptoms, reducing exacerbation frequency and severity, and improving health
      related quality-of-life. However, few clinical or laboratory markers specifically
      validated for bronchiectasis exist, and how best to assess the disease and its
      response to treatment is poorly understood. Pertinent, reliable markers are
      urgently needed to facilitate effective treatment of bronchiectasis and to ensure
      ongoing development of future therapies. This article explores the utility of
      potential end points in evaluating therapies used in the long-term management of
      stable bronchiectasis.

PMID- 22640850
TI  - Chest physiotherapy techniques in bronchiectasis.
AB  - Bronchiectasis is a persistent and progressive condition characterized by
      inflammation and infection causing damage that potentiates impaired mucociliary
      clearance. The rationale for promoting airway clearance is so that purulent
      secretions are removed from the airways, ameliorating the inflammation and
      improving control of symptoms such as cough and sputum plugging. Physiotherapists
      aim to teach patients one of a variety of airway clearance techniques to
      regularly perform as part of their daily management.

PMID- 22640851
TI  - Pharmacologic agents for mucus clearance in bronchiectasis.
AB  - There are no approved pharmacologic agents to enhance mucus clearance in non
      cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar
      agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing
      in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a
      mucolytic in other lung diseases. Dornase alpha is beneficial to patients with
      CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents
      such as beta-agonists have the potential to improve mucociliary clearance in
      normals and many disease states, but have not been adequately studied in patients
      with bronchiectasis.

PMID- 22640852
TI  - The use of antiinflammatory therapy and macrolides in bronchiectasis.
AB  - Airway inflammation is a major component of disease pathogenesis in
      bronchiectasis, suggesting that antiinflammatory therapies could be of benefit in
      treatment. This article addresses the use of anti-inflammatory/immunomodulatory
      therapies in the management of patients with bronchiectasis and individually
      discusses the use of corticosteroids, macrolides, and other potential anti
      inflammatory agents.

PMID- 22640853
TI  - Antimicrobial therapy for bronchiectasis.
AB  - Antibiotics have a role in the management of acute exacerbations of
      bronchiectasis and may also benefit selected subsets of patients with
      bronchiectasis as a part of a long-term maintenance strategy. At present, there
      are no Food and Drug Administration-approved antibiotics for acute or chronic
      management of bronchiectasis. Clinical trials are underway to determine the
      efficacy and safety of various inhaled antibiotics for chronic therapy for
      bronchiectasis. Until those results are available, clinicians need to tailor
      their therapies to individual patients based on their best clinical judgment and
      information from data and guidelines currently available in the published
      literature.

PMID- 22640854
TI  - Pulmonary resection and lung transplantation for bronchiectasis.
AB  - The purpose of this article is to update specialists in pulmonary medicine on the
      role of surgical resection and lung transplantation for bronchiectasis. The focus
      is on pre-operative workup, the technical details of surgical resection,
      complications, and outcomes.

PMID- 22640855
TI  - Preface. Bronchiectasis.

PMID- 22640856
TI  - Words of wisdom. Re: Combining 33 genetic variants with prostate-specific antigen
      for the prediction of prostate cancer: longitudinal study.

PMID- 22640857
TI  - Words of wisdom. Re: Disseminated prostate cancer cells can instruct
      hematopoietic stem and progenitor cells to regulate bone phenotype.

PMID- 22640858
TI  - Words of wisdom. Re: The role of endoscopic nephron-sparing surgery in the
      management of upper tract urothelial carcinoma.

PMID- 22640859
TI  - Words of wisdom. Re: Comparative effectiveness of axitinib versus sorafenib in
      advanced renal cell carcinoma (AXIS): a randomised phase 3 trial.

PMID- 22640860
TI  - Words of wisdom. Re: Phase III study of molecularly targeted adjuvant therapy in
      locally advanced urothelial cancer of the bladder based on p53 status.

PMID- 22640861
TI  - Words of wisdom. Re: Combination of adjuvant hormonal and radiation therapy
      significantly prolongs survival of patients with pT2-4 pN+ prostate cancer:
      results of a matched analysis.

PMID- 22640862
TI  - A high-throughput approach to identify genomic variants of bacterial metabolite
      producers at the single-cell level.
AB  - We present a novel method for visualizing intracellular metabolite concentrations
      within single cells of Escherichia coli and Corynebacterium glutamicum that
      expedites the screening process of producers. It is based on transcription
      factors and we used it to isolate new L-lysine producing mutants of C. glutamicum
      from a large library of mutagenized cells using fluorescence-activated cell
      sorting (FACS). This high-throughput method fills the gap between existing high
      throughput methods for mutant generation and genome analysis. The technology has
      diverse applications in the analysis of producer populations and screening of
      mutant libraries that carry mutations in plasmids or genomes.

PMID- 22640863
TI  - Proteomic identification of host and parasite biomarkers in saliva from patients
      with uncomplicated Plasmodium falciparum malaria.
AB  - BACKGROUND: Malaria cases attributed to Plasmodium falciparum account for
      approximately 600,000 deaths yearly, mainly in African children. The gold
      standard method to diagnose malaria requires the visualization of the parasite in
      blood. The role of non-invasive diagnostic methods to diagnose malaria remains
      unclear. METHODS: A protocol was optimized to deplete highly abundant proteins
      from saliva to improve the dynamic range of the proteins identified and assess
      their suitability as candidate biomarkers of malaria infection. A starch-based
      amylase depletion strategy was used in combination with four different lectins to
      deplete glycoproteins (Concanavalin A and Aleuria aurantia for N-linked
      glycoproteins; jacalin and peanut agglutinin for O-linked glycoproteins). A
      proteomic analysis of depleted saliva samples was performed in 17 children with
      fever and a positive-malaria slide and compared with that of 17 malaria-negative
      children with fever. RESULTS: The proteomic signature of malaria-positive
      patients revealed a strong up-regulation of erythrocyte-derived and inflammatory
      proteins. Three P. falciparum proteins, PFL0480w, PF08_0054 and PFI0875w, were
      identified in malaria patients and not in controls. Aleuria aurantia and jacalin
      showed the best results for parasite protein identification. CONCLUSIONS: This
      study shows that saliva is a suitable clinical specimen for biomarker discovery.
      Parasite proteins and several potential biomarkers were identified in patients
      with malaria but not in patients with other causes of fever. The diagnostic
      performance of these markers should be addressed prospectively.

PMID- 22640864
TI  - Molecular basis for sculpting the endoplasmic reticulum membrane.
AB  - The endoplasmic reticulum (ER) is involved in many critical processes, including
      protein and lipid synthesis and calcium storage. Morphologically, the ER can be
      divided into two subdomains: a network of interconnected tubules and interspersed
      sheets. Until recently, how these different compartments form in a continuous
      membrane system was unclear. Several classes of integral membrane proteins have
      been identified in the ER; the reticulons and DP1/Yop1p play roles in the
      generation of ER tubules, and possibly in stabilizing ER sheets, atlastins and
      Sey1p are dynamin-like GTPases that facilitate tubular network formation by
      mediating ER membrane fusion, and Climp63, p180, and kinectin are enriched in ER
      sheets and influence their formation. In this review, we summarize recent
      advances in our understanding of how these proteins participate in ER shaping. We
      also discuss possible mechanisms for regulating ER morphology via the
      cytoskeleton. Lessons learned about sculpting the ER membrane may be applicable
      to other organelles.

PMID- 22640866
TI  - Continuous equilibrium scores: factoring in the time before a fall.
AB  - The equilibrium (EQ) score commonly used in computerized dynamic posturography is
      normalized between 0 and 100, with falls assigned a score of 0. The resulting
      mixed discrete-continuous distribution limits certain statistical analyses and
      treats all trials with falls equally. We propose a simple modification of the
      formula in which peak-to-peak sway data from trials with falls is scaled
      according the percent of the trial completed to derive a continuous equilibrium
      (cEQ) score. The cEQ scores for trials without falls remain unchanged from the
      original methodology. The cEQ factors in the time before a fall and results in a
      continuous variable retaining the central tendencies of the original EQ
      distribution. A random set of 5315 Sensory Organization Test trials were pooled
      that included 81 falls. A comparison of the original and cEQ distributions and
      their rank ordering demonstrated that trials with falls continue to constitute
      the lower range of scores with the cEQ methodology. The area under the receiver
      operating characteristic curve (0.997) demonstrates that the cEQ retained near
      perfect discrimination between trials with and without falls. We conclude that
      the cEQ score provides the ability to discriminate between ballistic falls from
      falls that occur later in the trial. This approach of incorporating time and sway
      magnitude can be easily extended to enhance other balance tests that include fall
      data or incomplete trials.

PMID- 22640865
TI  - Urological outcomes in the omphalocele exstrophy imperforate anus spinal defects
      (OEIS) complex: experience with 80 patients.
AB  - OBJECTIVE: To review the urological management and outcomes of patients with the
      OEIS (omphalocele, exstrophy of the bladder, imperforate anus, spinal
      abnormalities) complex. PATIENTS AND METHODS: 80 patients with the OEIS complex
      managed at a single institution between 1974 and 2009 were reviewed. RESULTS: 37
      had initial closure at our institution (2 failed - 5%); 22 with successful
      closure were referred for incontinence; 15 failed closure at an outside
      institution (2 of whom are awaiting closure); 6 are skin-covered variants.
      Osteotomy was performed in 39/43 (91%) with successful closure versus 8/17 (47%)
      who failed initial bladder closure. 40 were dry (56%), but most needed additional
      urinary reconstruction: 2 had small bowel neobladders; 32 (84%) had augmentation
      cystoplasty; 30 (79%) had a continent catheterizable channel; only 9 (24%) were
      continent with an intact urethra. Bladder neck reconstruction allowed dryness in
      7 (18%). 45 patients had XY genotype--19 had female gender assignment at birth.
      All patients with XX genotype had female gender assignment. CONCLUSIONS:
      Osteotomy improves success of initial bladder closure. A bladder neck procedure,
      catheterizable channel, and augmentation cystoplasty will be required in the
      majority of patients to attain urinary dryness.

PMID- 22640867
TI  - Reproducibility of measures of leg muscle power, leg muscle strength, postural
      sway and mobility in people with Parkinson's disease.
AB  - Muscle power, muscle strength and postural sway are considered to be determinants
      of fall risk and gait in Parkinson's disease (PD) and potential targets for
      therapeutic trials. However, the potential usefulness of these tests as outcome
      measures depends on their reproducibility in the PD population. Therefore,
      measures of leg muscle power, leg muscle strength, postural sway and mobility
      were taken on two occasions 1 week apart in 31 people with PD. Measures of muscle
      power, muscle strength and mobility were found to be very reliable (intraclass
      correlation coefficients (ICC(3,1) 0.50-0.97)) and showed good agreement, i.e.
      small measurement error. Postural sway measures showed poor reliability (ICC(3,1)
      0.04-0.51) and agreement, especially in the presence of disabling dyskinesia. The
      moderate to high reproducibility of leg muscle power, muscle strength and
      mobility measures in people with PD confirm their suitability as outcomes
      measures in clinical and research settings. Further research into the clinical
      measurement of postural sway in people with PD is warranted, especially in
      individuals with dyskinesia.

PMID- 22640868
TI  - Automatic Fortran to C++ conversion with FABLE.
AB  - BACKGROUND: In scientific computing, Fortran was the dominant implementation
      language throughout most of the second part of the 20th century. The many tools
      accumulated during this time have been difficult to integrate with modern
      software, which is now dominated by object-oriented languages. RESULTS: Driven by
      the requirements of a large-scale scientific software project, we have developed
      a Fortran to C++ source-to-source conversion tool named FABLE. This enables the
      continued development of new methods even while switching languages. We report
      the application of FABLE in three major projects and present detailed comparisons
      of Fortran and C++ runtime performances. CONCLUSIONS: Our experience suggests
      that most Fortran 77 codes can be converted with an effort that is minor
      (measured in days) compared to the original development time (often measured in
      years). With FABLE it is possible to reuse and evolve legacy work in modern
      object-oriented environments, in a portable and maintainable way. FABLE is
      available under a nonrestrictive open source license. In FABLE the analysis of
      the Fortran sources is separated from the generation of the C++ sources.
      Therefore parts of FABLE could be reused for other target languages.

PMID- 22640869
TI  - Capacitative and non-capacitative signaling complexes in human platelets.
AB  - Discharge of the intracellular Ca(2+) stores activates Ca(2+) entry through store
      operated channels (SOCs). Since the recent identification of STIM1 and STIM2, as
      well as the Orai1 homologs, Orai2 and Orai3, the protein complexes involved in
      Ca(2+) signaling needs re-evaluation in native cells. Using real time PCR
      combined with Western blotting we have found the expression of the three Orai
      isoforms, STIM1, STIM2 and different TRPCs in human platelets. Depletion of the
      intracellular Ca(2+) stores with thapsigargin, independently of changes in
      cytosolic Ca(2+) concentration, enhanced the formation of a signaling complex
      involving STIM1, STIM2, Orai1, Orai2 and TRPC1. Furthermore, platelet treatment
      with the dyacylglicerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) resulted in
      specific association of Orai3 with TRPC3. Treatment of platelets with arachidonic
      acid enhanced the association between Orai1 and Orai3 in human platelets and
      overexpression of Orai1 and Orai3 in HEK293 cells increased arachidonic acid
      induced Ca(2+) entry. These results indicate that Ca(2+) store depletion results
      in the formation of exclusive signaling complexes involving STIM proteins, as
      well as Orai1, Orai2 and TRPC1, but not Orai3, which seems to be involved in non
      capacitative Ca(2+) influx in human platelets.

PMID- 22640870
TI  - Sulforaphane, a cruciferous vegetable-derived isothiocyanate, inhibits protein
      synthesis in human prostate cancer cells.
AB  - Sulforaphane (SFN) is a compound derived from cruciferous plants. Its anticancer
      properties have been demonstrated both, in cancer cell lines as well as tumors in
      animal models. It has been shown that SFN inhibits cell proliferation, induces
      apoptosis, autophagy, and sensitizes cancer cells to therapies. As induction of
      catabolic processes is often related to perturbation in protein synthesis we
      aimed to investigate the impact of SFN on this process in PC-3 human prostate
      cancer cells. In the present study we show that SFN inhibits protein synthesis in
      PC-3 cells in a dose- and time-dependent manner which is accompanied by a
      decreased phosphorylation of mTOR substrates. Translation inhibition is
      independent of mitochondria-derived ROS as it is observed in PC-3 derivatives
      devoid of functional mitochondrial respiratory chain (Rho0 cells). Although SFN
      affects mitochondria and slightly decreases glycolysis, the ATP level is
      maintained on the level characteristic for control cells. Inhibition of protein
      synthesis might be a protective response of prostate cancer cells to save energy.
      However, translation inhibition contributes to the death of PC-3 cells due to
      decreased level of a short-lived protein, survivin. Overexpression of this anti
      apoptotic factor protects PC-3 cells against SFN cytotoxicity. Protein synthesis
      inhibition by SFN is not restricted to prostate cancer cells as we observed
      similar effect in SKBR-3 breast cancer cell line.

PMID- 22640871
TI  - The prevalence and predictors of anxiety and depression in adolescents with heart
      disease.
AB  - OBJECTIVE: To evaluate the prevalence and contributory factors of depression and
      anxiety in adolescents with heart disease. STUDY DESIGN: A cohort of adolescents
      was recruited from an ambulatory cardiology clinic at a tertiary center and from
      such clinics run privately. Questionnaires included the Hospital Anxiety and
      Depression Scale, Multidimensional Scale of Perceived Social Support, Life
      Orientation Test-Revised, and Sense of Coherence-13. RESULTS: A total of 119
      adolescents aged 12-20 years were recruited. Most of the participants (90%) had
      congenital heart disease. Nearly all (98%) were in New York Heart Association
      Functional Classification class I. Approximately one-half of the participants had
      had previous surgeries and/or catheter interventions. Eleven patients (9%) were
      above the cut-off score for likely depression, and 32 (27%) had likely anxiety. A
      feeling of optimism was the most significant factor in reducing anxiety and
      depression, followed by good social support and a strong sense of coherence
      (multiple regressions, beta = -0.38, -0.2, -0.17, respectively). CONCLUSIONS:
      Depression and anxiety were found to be common in a relatively well adolescent
      population with heart disease. None of those affected had been clinically
      assessed and appropriately treated by a mental health professional. Protective
      factors against depression and anxiety need be developed as well as appropriate
      assessment and intervention.

PMID- 22640872
TI  - Uncoordinated sucking patterns in preterm infants are associated with abnormal
      general movements.
AB  - OBJECTIVE: To examine the association between sucking patterns and the quality of
      fidgety movements in preterm infants. STUDY DESIGN: We studied the sucking
      patterns and fidgety movements of 44 preterm infants (gestational age <35 weeks)
      longitudinally from 34 weeks' postmenstrual age up to 14 weeks postterm. We used
      the Neonatal Oral-Motor Assessment Scale during feeding and scored the sucking
      patterns as normal or abnormal. Abnormal sucking patterns were categorized into
      arrhythmic sucking and uncoordinated sucking. At 14 weeks postterm, we scored the
      quality of fidgety movements from videotapes as normal, abnormal, or absent.
      RESULTS: The postmenstrual age at which sucking patterns became normal (median,
      48 weeks; range, 34 to >50 weeks) was correlated with the quality of fidgety
      movements (Spearman rho = -0.33; P = .035). The percentage per infant of normal
      and uncoordinated sucking patterns was also correlated with the quality of
      fidgety movements (rho = 0.31; P = .048 and rho = -0.33; P = .032, respectively).
      Infants with uncoordinated sucking patterns had a higher rate of abnormal fidgety
      movements (OR, 7.5; 95% CI, 1.4-40; P = .019). CONCLUSION: The development of
      sucking patterns in preterm infants was related to the quality of fidgety
      movements. Uncoordinated sucking patterns were associated with abnormal fidgety
      movements, indicating that uncoordinated sucking, swallowing, and breathing may
      represent neurologic dysfunction.

PMID- 22640873
TI  - Infertility in male aquatic invertebrates: a review.
AB  - As a result of endocrine disruptor studies, there are numerous examples of male
      related reproductive abnormalities observed in vertebrates. Contrastingly, within
      the invertebrates there have been considerably less examples both from laboratory
      and field investigations. This has in part been due to a focus of female related
      endpoints, inadequate biomarkers and the low number of studies. Whether
      contaminant induced male infertility is an issue within aquatic invertebrates and
      their wider communities therefore remains largely unknown and represents a key
      knowledge gap in our understanding of pollutant impacts in aquatic wildlife. This
      paper reviews the current knowledge regarding pollutants impacting male
      infertility across several aquatic invertebrate phyla; which biomarkers are
      currently being used and where the science needs to be expanded. The limited
      studies conducted so far have revealed reductions in sperm numbers, examples of
      poor fertilisation success, DNA damage to spermatozoa and inhibition of sperm
      motility that can be induced by a range of environmental contaminants. This
      limited data is mainly comprised from laboratory studies with only a few studies
      of sperm toxicity in natural populations. Clearly, there is a need for further
      studies in this area, to include both laboratory and field studies from clean and
      reference sites, with a focus on broadcast spawners and those with direct
      fertilisation. Biomarkers developed for measuring sperm quantity and quality in
      vertebrates are easily transferable to invertebrates but require optimisation for
      particular species. We discuss how sperm tracking and techniques for measuring
      DNA strand breaks and sperm viability have been successfully transferred from
      human infertility clinics to aquatic invertebrate ecotoxicology. Linking sperm
      toxicity and male infertility effects to higher level impacts on the reproductive
      biology and dynamics of populations requires a much greater understanding of
      fertilisation dynamics and sperm competition/limitation for invertebrate species
      and represents the next challenge in our understanding of male toxicity effects
      in natural populations.

PMID- 22640874
TI  - Hepatic antioxidative responses to PCDPSs and estimated short-term biotoxicity in
      freshwater fish.
AB  - This study evaluated the short-term toxicity of polychlorinated diphenylsulfides
      (PCDPSs) in freshwater fish. Laboratory experiments were performed to determine
      the oxidative stress and antioxidative responses of 12 different types of PCDPSs
      in the liver of goldfish, Carassius auratus. Fish were injected with increasing
      concentrations (0.1, 1, 10, 100 MUg/kg body weight for various PCDPSs and 1, 10,
      100 mg/kg for diphenylsulfides (DPS)) of test compounds for 12h, with one group
      assigned as the control. We simultaneously evaluated the time-dependent effects
      of PCDPSs on the antioxidant defense system, using Tris-, Penta- and Hepta-CDPS.
      Fish were acutely injected with either 10 MUg/kg of such PCDPSs or corn oil alone
      (control), and then liver samples were collected at 0.5, 1, 2, 3 and 5d for
      analysis of antioxidant content. Changes in the activities of superoxide
      dismutase (SOD), catalase (CAT), and in the levels of malondialdehyde (MDA) were
      detected, suggesting that PCDPSs exhibit potential biotoxicity. In addition, our
      data indicated that PCDPS toxicity varies with the degree of substitution and the
      position of substitution attached to two benzene rings, results that were also
      partly supported by the time-dependent effects elicited by the Tris-, Penta- and
      Hepta-CDPSs. In particular, our results indicate that Penta- and Hexa-CDPSs may
      act as highly toxic contaminants that exhibit striking enzymatic inhibitory
      activity. Furthermore, our results suggest that altered levels of antioxidant
      enzymes, including SOD and CAT, along with MDA, may serve as potential biomarkers
      of PCDPS contamination.

PMID- 22640875
TI  - Radioprobing the conformation of DNA in a p53-DNA complex.
AB  - PURPOSE: The frequency of DNA strand breaks produced by the decay of Auger
      electron-emitting radionuclides is inversely proportional to the distance of DNA
      nucleotides from the decay site; and thus is very sensitive to changes in the
      local conformation of the DNA. Analysis of the frequency of DNA breaks, or
      radioprobing, gives valuable information about the local DNA structure. More than
      10 years ago, we demonstrated the feasibility of radioprobing using a DNA
      repressor complex with a known structure. Herein, we used radioprobing to study
      the conformation of DNA in complex with the tumor suppressor protein 53 (p53).
      Several structures of p53-DNA complexes have been solved by X-ray
      crystallography. These structures, obtained with the p53 DNA binding domain, a
      truncated form, laid the groundwork for understanding p53-DNA interactions and
      their relation to p53 functions. However, whether all observed stereochemical
      details are relevant to the native p53-DNA complex remains unclear. A common
      theme of the crystallographic structures is the lack of significant bending in
      the central part of the DNA response element. In contrast, gel electrophoresis
      and electron microscopy data showed strong DNA bending and overtwisting upon
      binding to the native p53 tetramer. METHODS: To analyze DNA in complex with p53,
      we incorporated (125)I-dCTP in two different positions of synthetic duplexes
      containing the consensus p53-binding site. RESULTS: The most significant changes
      in the break frequency distributions were detected close to the center of the
      binding site, which is consistent with an increase in DNA twisting in this region
      and local DNA bending and sliding. CONCLUSIONS: Our data confirm the main results
      of the studies made in solution and lay a foundation for systematic examination
      of interactions between DNA and native p53 using (125)I radioprobing.

PMID- 22640876
TI  - Deletion of selenoprotein P results in impaired function of parvalbumin
      interneurons and alterations in fear learning and sensorimotor gating.
AB  - One of the primary lines of defense against oxidative stress is the selenoprotein
      family, a class of proteins that contain selenium in the form of the 21st amino
      acid, selenocysteine. Within this class of proteins, selenoprotein P (Sepp1) is
      unique, as it contains multiple selenocysteine residues and is postulated to act
      in selenium transport. Recent findings have demonstrated that neuronal
      selenoprotein synthesis is required for the development of parvalbumin (PV)
      interneurons, a class of GABAergic neurons involved in the synchronization of
      neural activity. To investigate the potential influence of Sepp1 on PV
      interneurons, we first mapped the distribution of the Sepp1 receptor, ApoER2, and
      parvalbumin in the mouse brain. Our results indicate that ApoER2 is highly
      expressed on PV-interneurons in multiple brain regions. Next, to determine
      whether PV-interneuron populations are affected by Sepp1 deletion, we performed
      stereology on several brain regions in which we observed ApoER2 expression on PV
      interneurons, comparing wild-type and Sepp1(-/-) mice. We observed reduced
      numbers of PV-interneurons in the inferior colliculus of Sepp1(-/-) mice, which
      corresponded with a regional increase in oxidative stress. Finally, as impaired
      PV-interneuron function has been implicated in several neuropsychiatric
      conditions, we performed multiple behavioral tests on Sepp1(-/-) mice. Our
      behavioral results indicate that Sepp1(-/-) mice have impairments in contextual
      fear extinction, latent inhibition, and sensorimotor gating. In sum, these
      findings demonstrate the important supporting role of Sepp1 on ApoER2-expressing
      PV-interneurons.

PMID- 22640877
TI  - Non-invasive prenatal diagnosis of aneuploidies: new technologies and clinical
      applications.
AB  - Non-invasive prenatal diagnosis (NIPD) has substantial medical importance as it
      targets the development of safer and more effective methods to avoid the risk of
      fetal loss associated with currently used invasive methods. Several approaches
      have been demonstrated as being proof-of concept for NIPD of chromosomal
      aneuploidies. These approaches include cell-based and cell-free detection
      methods, involving the investigation of fetal cells in the maternal circulation,
      formaldehyde treatment of maternal plasma, DNA methylation studies using sodium
      bisulfite or restriction enzymes, protein-based studies, identification of fetal
      specific mRNAs and digital polymerase chain reaction (PCR) approaches, and
      recently next-generation sequencing and methylated DNA immunoprecipitation real
      time quantitative PCR-based approaches. Although all these NIPD methods have both
      advantages and limitations, some are moving closer to clinical implementation.
      Biotechnology companies dedicated to the development of NIPD tests such as the
      sequencing- or methylation-based approaches are finalizing large clinical trials.
      It is expected that these new technologies will facilitate safer, more sensitive
      and accurate prenatal diagnostic tests in the near future. In this review, we
      highlight the most recent advances in methods for NIPD of aneuploidies, and we
      discuss their future implications in clinical practice.

PMID- 22640879
TI  - Bio-samtools: Ruby bindings for SAMtools, a library for accessing BAM files
      containing high-throughput sequence alignments.
AB  - BACKGROUND: The SAMtools utilities comprise a very useful and widely used suite
      of software for manipulating files and alignments in the SAM and BAM format, used
      in a wide range of genetic analyses. The SAMtools utilities are implemented in C
      and provide an API for programmatic access, to help make this functionality
      available to programmers wishing to develop in the high level Ruby language we
      have developed bio-samtools, a Ruby binding to the SAMtools library. RESULTS: The
      utility of SAMtools is encapsulated in 3 main classes, Bio::DB::Sam, representing
      the alignment files and providing access to the data in them, Bio::DB::Alignment,
      representing the individual read alignments inside the files and Bio::DB::Pileup,
      representing the summarised nucleotides of reads over a single point in the
      nucleotide sequence to which the reads are aligned. CONCLUSIONS: Bio-samtools is
      a flexible and easy to use interface that programmers of many levels of
      experience can use to access information in the popular and common SAM/BAM
      format.

PMID- 22640880
TI  - Cadmium-induced changes in genomic DNA-methylation status increase aneuploidy
      events in a pig Robertsonian translocation model.
AB  - Although cadmium is a well-established human carcinogen, the mechanisms by which
      it induces cancer are poorly understood. It is suggested that cadmium-mediated
      carcinogenesis may include the modulation of gene expression and signal
      transduction pathways, interference with antioxidant enzymes, inhibition of DNA
      repair and DNA methylation, and induction of apoptosis. Nevertheless, no
      predominant mechanism playing a role in metal-induced carcinogenesis has been
      reported. In the present study, we used a pig Robertsonian translocation model,
      which is a cross between a wild boar and domestic pig resulting in Robertsonian
      translocation (37,XX,der15;17 or 37,XY,der15;17), to determine the role of
      cadmium sulfate in the modulation of genomic DNA-methylation status and the
      induction of aneuploidy. We found a cadmium-mediated increase in aneuploidy
      within chromosome group A and C, but not within chromosome group D containing the
      translocated chromosome der15,17 which indicates that translocated chromosome is
      not more prone to chromosomal aberrations than are other chromosomes. We suggest
      that cadmium-induced aneuploidy (up to 5-MUM concentration) may be mediated by
      global DNA hypermethylation as monitored with HPLC and 5-mdC immunostaining. In
      addition, the cyto- and genotoxic potential of cadmium was evaluated. Cadmium
      sulfate was able to induce apoptosis, inhibit cell-proliferative status and
      expression of nucleolar organizer regions (NORs), and increase oxidative DNA
      damage (8-oxoG content).

PMID- 22640878
TI  - beta3 integrin modulates transforming growth factor beta induced (TGFBI) function
      and paclitaxel response in ovarian cancer cells.
AB  - BACKGROUND: The extracellular matrix (ECM) has a key role in facilitating the
      progression of ovarian cancer and we have shown recently that the secreted ECM
      protein TGFBI modulates the response of ovarian cancer to paclitaxel-induced cell
      death. RESULTS: We have determined TGFBI signaling from the extracellular
      environment is preferential for the cell surface alphavbeta3 integrin
      heterodimer, in contrast to periostin, a TGFBI paralogue, which signals primarily
      via a beta1 integrin-mediated pathway. We demonstrate that suppression of beta1
      integrin expression, in beta3 integrin-expressing ovarian cancer cells, increases
      adhesion to rTGFBI. In addition, Syndecan-1 and -4 expression is dispensable for
      adhesion to rTGFBI and loss of Syndecan-1 cooperates with the loss of beta1
      integrin to further enhance adhesion to rTGFBI. The RGD motif present in the
      carboxy-terminus of TGFBI is necessary, but not sufficient, for SKOV3 cell
      adhesion and is dispensable for adhesion of ovarian cancer cells lacking beta3
      integrin expression. In contrast to TGFBI, the carboxy-terminus of periostin,
      lacking a RGD motif, is unable to support adhesion of ovarian cancer cells.
      Suppression of beta3 integrin in SKOV3 cells increases resistance to paclitaxel
      induced cell death while suppression of beta1 integrin has no effect.
      Furthermore, suppression of TGFBI expression stimulates a paclitaxel resistant
      phenotype while suppression of fibronectin expression, which primarily signals
      through a beta1 integrin-mediated pathway, increases paclitaxel sensitivity.
      CONCLUSIONS: Therefore, different ECM components use distinct signaling
      mechanisms in ovarian cancer cells and in particular, TGFBI preferentially
      interacts through a beta3 integrin receptor mediated mechanism to regulate the
      response of cells to paclitaxel-induced cell death.

PMID- 22640881
TI  - Genotoxicity testing of combined treatment with cisplatin, bleomycin, and 5
      fluorouracil in somatic cells of Drosophila melanogaster.
AB  - The simultaneous treatment with the cross-linking agent cisplatin, the
      radiomimetic antitumoral drug bleomycin, and the anti-metabolite drug 5
      fluorouracil has been used as a regimen to treat patients with squamous cell
      carcinoma of the head and neck. Considering that these drugs interact directly
      with DNA, one of the important late-occurring complications from treatment of
      primary malignancies is the therapy-related secondary cancers as a result of the
      genotoxic activity of the drugs on normal cells. In this sense, the genotoxicity
      of this combination was evaluated using the wing somatic mutation and
      recombination test in Drosophila melanogaster. The mutant spots observed in
      marker-heterozygous and balancer-heterozygous flies were compared in order to
      quantitatively and qualitatively estimate the genotoxic effect of these drugs.
      Cisplatin (0.003 and 0.006mM), bleomycin (0.005 and 0.01mM), and both
      combinations preferentially induced recombinational events, while mutation is the
      major event regarding the genetic toxicity of 5-fluorouracil (0.025 and 0.05mM).
      The combination of these drugs produced synergistic and antagonistic genotoxic
      effects, depending on the concentrations used, which could impose a higher risk
      of secondary effects associated with their genotoxic effects, emphasizing the
      importance of long-term monitoring in patients being treated with these drugs.

PMID- 22640882
TI  - Exposure of thermoelectric power-plant workers to volatile organic compounds from
      fuel oil: genotoxic and cytotoxic effects in buccal epithelial cells.
AB  - Thermoelectric power-plant workers are constantly exposed to high levels of
      potentially genotoxic gaseous substances, such as volatile organic compounds
      (VOCs) from the combustion of fuel oil or the processing of naphtha. The aim of
      the present study was to estimate the association between such occupational
      exposure and the frequency of micronucleated cells and cells with other nuclear
      anomalies. Buccal epithelial cells were collected from a total of 44 power-plant
      workers (exposed group) and 47 administrative workers (non-exposed group), and
      examined for the frequency of micronucleated cells (MNC) and of cells with other
      nuclear anomalies (ONA: pyknosis, karyolysis, and karyorrhexis) by means of the
      micronucleus assay. The frequencies of MNC and ONA per 1000 cells in the exposed
      group (1.80/00 and 82.40/00, respectively) were significantly higher than in the
      non-exposed group (0.20/00 and 58.30/00, respectively). The exposed group had a
      twelve-fold increase in risk for formation of MNC compared with non-exposed
      individuals (RR=12.1; 95% CI, 5.0-29.2; P<0.001). The confounding factors
      analyzed (age, smoking status, alcohol consumption, and mouthwash use) did not
      show any significant association with the frequency of MNC or ONA. The findings
      of this study show that workers from power plants exposed to VOCs have a
      significantly elevated risk for DNA damage. Therefore, bio-monitoring of DNA
      damage is recommended for this group of workers.

PMID- 22640883
TI  - Genotoxicity and cellular uptake of cyclotides: evidence for multiple modes of
      action.
AB  - Cyclotides are a family of ultra-stable, head-to-tail cyclic mini-proteins from
      plants, with each member comprising about 30 amino acid residues. Their stability
      derives from the unique structural topology where the cyclic backbone and two
      disulfide bonds make up an embedded ring, which is knotted by a third disulfide
      bond. The cyclotides find potential applications in the pharmaceutical industry
      as stable peptide-based scaffolds for unstable drugs, and also as medicinal
      agents, due to the wide range of their inherent pharmacological activities.
      However, there is a lack of fundamental toxicological studies on this type of
      compound. The current study determined the possible DNA-damaging effects of three
      cyclotides, i.e., cycloviolacin O2, vaby D, and kalata B1, in human lymphoma
      cells by use of the alkaline version of the comet assay. The three cyclotides
      induced massive DNA fragmentation at lethal concentrations. At a sub-lethal
      concentration, cycloviolacin O2 and vaby D gave a bell-shaped dose-response curve
      for their DNA-damaging effect. Kalata B1 caused no significant DNA damage at sub
      cytotoxic concentrations. Single-cell micro-autoradiography was carried out on
      tritium-labeled cycloviolacin O2 in order to understand the mechanism behind the
      dose-response curve. The results revealed that the peptide is taken up into the
      cell, both at cytotoxic and at low concentrations. Most biological effects of the
      cyclotides have been taken to follow from the disruption of cell membranes, but
      even if the intracellular mechanisms and targets still remain unknown, the
      current study has unequivocally demonstrated that cyclotides also must have other
      dose-dependent modes of action.

PMID- 22640884
TI  - Investigations on the binding of human hemoglobin with orange I and orange II.
AB  - The interactions between human hemoglobin and orange I (or orange II) were
      investigated by UV/vis absorption, circular dichroism, fluorescence spectra
      techniques, and molecular modeling method. Orange I and orange II effectively
      quenched the intrinsic fluorescence of human hemoglobin by static quenching. The
      processes of the binding orange I and orange II on human hemoglobin were
      spontaneous molecular interaction procedure with hydrogen bonds, van der Waals
      force, hydrophobic and electrostatic interactions according to van't Hoff
      equation and molecular modeling. There is a single class of binding site of
      orange I (orange II) in human hemoglobin and the molecular modeling study shows
      that orange I and orange II are dipped into alpha(2) chain. The results of CD,
      synchronous fluorescence and three-dimensional fluorescence spectra indicated a
      small loss of alpha-helical secondary structure of human hemoglobin induced by
      orange I and orange II.

PMID- 22640885
TI  - Using focus groups to identify factors affecting healthful weight maintenance in
      Latino immigrants.
AB  - OBJECTIVE: To explore (1) how migration influenced physical activity and dietary
      behaviors among Latino immigrants and (2) participants' perception of concepts
      related to a Health at Every Size (HAES) approach to weight maintenance (mindful
      eating, taking care of oneself). METHODS: Four focus groups (n = 35), homogenous
      by sex, were conducted in Spanish. RESULTS: Male and female participants spoke of
      being less physically active and eating less healthful diets since immigrating.
      Noted barriers to being physically active and eating a healthful diet included
      time and financial constraints. Participants were interested in the HAES concepts
      but thought these ideas conflicted with their cultural upbringing. For women,
      putting family first was identified as a barrier to taking care of oneself.
      CONCLUSIONS AND IMPLICATIONS: An HAES approach may be a useful in promoting
      weight maintenance in this population, as participants were interested in key
      concepts, but it would be important that HAES interventions incorporate cultural
      traditions.

PMID- 22640886
TI  - Retraction notice to "Proton-pumping-ATPase-targeted antifungal activity of
      cinnamaldehyde based sulfonyl tetrazoles" [Eur. J. Med. Chem. 48 (2012) 363-370].

PMID- 22640887
TI  - Caroli disease patients have excellent survival after liver transplant.
AB  - BACKGROUND: Caroli disease (CD) is characterized by dilation of the intrahepatic
      biliary tree, which may result in malignancy. Treatments include management of
      symptoms and hepatic resection to decrease disease burden. In patients with CD
      not amenable to these treatments, orthotopic liver transplantation (OLT) has been
      used. This study examines if OLT is a reasonable treatment for patients with CD.
      MATERIALS AND METHODS: The United Network of Organ Sharing/Organ Procurement and
      Transplantation Network database between September 30, 1987 and March 31, 2011
      was queried. Cases without patient or allograft survival time or without a
      diagnosis were excluded from analysis. Patients with CD were compared to patients
      with primary biliary cirrhosis (PBC), secondary biliary cirrhosis (BC), primary
      sclerosing cholangitis (PSC), and all indications for OLT. Survival analysis was
      performed by log-rank test and Kaplan-Meier. RESULTS: One hundred forty patients
      with CD were compared to 4797 patients with PBC, 489 patients with secondary BC,
      6033 patients with PSC, and 92,210 patients post-OLT. Patient and allograft
      survivals of CD patients at 1, 3, 5, and 10 y are, respectively, 88.5%, 83.4%,
      80.9%, and 77.8%; and 81.2%, 74.8%, 70.6%, and 67.9%. CD patients have
      significantly improved patient and allograft survivals after OLT compared to
      patients with secondary BC (P = 0.003, P = 0.015) and all other patients
      undergoing OLT (P = 0.003, P = 0.026). There is a trend towards long-term
      improved patient and allograft survival in transplanted patients with CD compared
      to patients with PBC and PSC. CONCLUSIONS: These results suggest that OLT should
      be considered an effective treatment modality for patients with CD resulting in
      excellent long-term outcomes.

PMID- 22640888
TI  - Inhibition of experimental abdominal aortic aneurysm in a rat model by way of
      tanshinone IIA.
AB  - BACKGROUND: The purpose of the present study was to investigate whether
      tanshinone IIA (Tan IIA), one of the major lipophilic components of Salvia
      miltiorrhiza Bunge, could inhibit the development of elastase-induced
      experimental abdominal aortic aneurysms (AAAs). METHODS: Male Sprague-Dawley rats
      (n = 12/group) were randomly distributed into three groups: Tan IIA, control, and
      sham. The rats from the Tan IIA and control groups underwent intra-aortic
      elastase perfusion to induce AAAs, and the rats in the sham group were perfused
      with saline. Only the Tan IIA group received Tan IIA (2 mg/rat/d). The maximum
      luminal diameter of the abdominal aorta was measured before and 5, 12, 18, and 24
      d after perfusion. The systolic blood pressure was measured twice using the tail
      cuff technique before administration and death. Aortic tissue samples were
      harvested at 24 d and evaluated using reverse transcriptase-polymerase chain
      reaction, Western blot, immunohistochemistry, and Miller's elastin-Van Gieson
      staining. RESULTS: The rats in the control group had significantly increased
      aortic sizes compared with the sham group after 24 days (P < 0.05), and the Tan
      IIA group had a significant reduction in aortic size (Tan IIA versus control, P <
      0.05) without affecting blood pressure (P > 0.05). The overexpression of matrix
      metalloproteinase-2, metalloproteinase-9, monocyte chemotactic protein-1, and
      inducible nitric oxide synthase and the depletion of elastic fibers and vascular
      smooth muscle cells induced by elastase perfusion were significantly decreased by
      Tan IIA treatment (P < 0.05). CONCLUSIONS: Tan IIA inhibited the development of
      elastase-induced experimental AAAs by suppressing proteolysis, inflammation, and
      oxidative stress and preserving vascular smooth muscle cells. It could be a new
      pharmacologic therapy for AAAs.

PMID- 22640889
TI  - Commentary on "Prophylaxis against HBV recurrence after liver transplantation for
      HBV-related endstage liver diseases with severe hypersplenism and splenomegaly:
      Role of splenectomy".

PMID- 22640890
TI  - [TRP calcium channel and breast cancer: expression, role and correlation with
      clinical parameters].
AB  - Breast cancer (BC) has the highest incidence rate in women in industrialized
      countries. Statistically, it is estimated that one out of 10 women will develop
      BC during her life. Evidence is accumulating for the role of ion channels in the
      development of cancer. Most studied ion channels in BC are K(+) channels, which
      are involved in cell proliferation, cell cycle progression and cell migration,
      and Na(+) channels, which correlate with invasiveness. Emerging studies
      demonstrated the role of Ca(2+) signaling in cancer cell proliferation, survival
      and migration. Recent findings demonstrated that the expression and/or activity
      of the transient receptor potential (TRP) channels are altered in several
      cancers. Among the TRP families, TRPC (canonical or classical), TRPM (melastatin)
      and TRPV (vanilloid) are related to malignant growth and cancer progression.
      Although these channels are frequently and abundantly expressed in many tumors,
      their specific expression, activity and roles in BC are still poorly understood.
      The expression of TRP channels has also been proposed as a tool for diagnosis,
      prognosis and/or therapeutic issues of several diseases. In cancer, TRPV6 and
      TRPM8 have been proposed as tumor progression markers of prostate cancer outcome
      and TRPC6 as a novel therapeutic target for esophageal carcinoma. Interestingly
      high levels of TRPC3 expression correlate with a favorable prognosis in patients
      with lung adenocarcinoma. Our team has recently reported the expression and role
      of TRPC1, TRPC6, TRPM7, TRPM8 and TRPV6 in BC cell lines and primary cultures. We
      have also investigated TRP expression and their clinical significance in human
      breast adenocarcinoma and we suggest that TRP channels are new potential BC
      markers. Indeed TRPC1 and TRPM8 may be considered as good prognosis markers of
      well-differentiated tumors, TRPM7 as a proliferative marker of poorly
      differentiated tumors and TRPV6 as a prognosis marker of aggressive cancers. In
      this review, we summarize the data reported to date regarding the changes in TRP
      expression associated with BC. We also discuss the importance of TRP channels in
      BC cells proliferation and migration and their interest as new BC markers.

PMID- 22640891
TI  - Improving oligonucleotide fingerprinting of rRNA genes by implementation of
      polony microarray technology.
AB  - Improvements to oligonucleotide fingerprinting of rRNA genes (OFRG) were obtained
      by implementing polony microarray technology. OFRG is an array-based method for
      analyzing microbial community composition. Polonies are discrete clusters of DNA,
      produced by solid-phase PCR in hydrogels, and derived from individual, spatially
      isolated DNA molecules. The advantages of a polony-based OFRG method include
      higher throughput and reductions in the PCR-induced errors and compositional skew
      inherent in all other PCR-based community composition methods, including high
      throughput sequencing of rRNA genes. Given the similarities between polony
      microarrays and certain aspects of sequencing methods such as the Illumina
      platform, we suggest that if concepts presented in this study were implemented in
      high-throughput sequencing protocols, a reduction of PCR-induced errors and
      compositional skew may be realized.

PMID- 22640892
TI  - Enhancement of lipid stability of broiler breast meat and meat products fed on
      alpha lipoic acid and alpha tocopherol acetate supplemented feed.
AB  - This study was designed to investigate the effect of alpha lipoic acid (ALA) and
      alpha tocopherol acetate (ATA) on the antioxidant potential, lipid stability and
      the quality of the broiler breast meat and meat products. The treatment plan was
      as (T1=control feed, T2=200 mg ATA + 25 mg ALA/kg feed, T3=200 mg ATA + 75 mg
      ALA/kg feed, T4=200 mg ATA +150 mg ALA/kg feed, T5=Oxidized oil (4%), T6=200 mg
      ATA + 150 mg ALA + Oxidized oil (4%)/kg feed). After two weeks of acclimatization
      the birds were fed with ALA and ATA enriched diet. The results revealed that
      maximum deposition of ALA took place in T4 which contain maximum dose of ALA. The
      TBARS and DPPH values of the broiler breast meat were in T4 (0.14 +/- 0.01 MDA/kg
      of meat, 76.69 +/- 0.14%) and in T5 were (0.24 +/- 0.15 MDA/Kg of meat, 44.98 +/-
      0.04%) accordingly. ATA concentration were also highest in T4 (206.43 +/- 0.22
      mg/g of meat) and lowest in T5 (79.09 +/- 0.06 mg/g of meat). Sensory evaluation
      results showed that nuggets and patties made of T5 containing oxidized oil were
      least liked and T4 got highest score. In a nutshell, 150 mg/kg feed dietary
      supplementation of ALA with constant level of ATA can ameliorate the antioxidant
      potential, lipid stability and nutritional qualities of broiler breast meat and
      meat products.

PMID- 22640893
TI  - Structural characterization of N-linked oligosaccharides on monoclonal antibody
      Nimotuzumab through process development.
AB  - Nimotuzumab (TheraCIM, CIMAher, h-R3, humanized anti-EGF-R antibody), monoclonal
      antibody (mAb) manufactured at the Center of Molecular Immunology (Havana, Cuba)
      is currently being tested in several clinical trials. Nimotuzumab has a single N
      glycosylation site in the Fc-CH2 fragment but no N-glycosylation site in the Fab
      region. The current study reports the full characterization of the mAb N
      glycosylation and the consistency observed in several production batches from a
      perfusion mode culturing system that lasted between 68 and 150 days. It confirms
      that the N-glycan structures of Nimotuzumab expressed in the NS0 murine myeloma
      cell line are of the murine type. They consist mainly of fucosylated G0, G1 and
      G2 oligosaccharides, which are normally found in the CH2 region of IgG. Other
      minor species found were high mannose and sialylated structures. A small portion
      of the glycans were sialylated (~12%) and the only type of sialic acid detected
      was N-glycolyl-sialic acid, alpha2,6-linked to Gal. No Galalpha1-3Gal moieties
      were detected.

PMID- 22640894
TI  - Predictors of recovery of left ventricular dysfunction after ablation of frequent
      ventricular premature depolarizations.
AB  - BACKGROUND: Frequent ventricular premature depolarizations (VPDs) can cause
      reversible left ventricular (LV) dysfunction. However, not all patients normalize
      their LV function after VPD elimination. OBJECTIVE: To evaluate predictors of
      recovery of LV function following the elimination of frequent VPDs. METHODS: We
      identified patients with >=10% VPDs/24 h and an LV ejection fraction of <50% who
      underwent successful ablation between 2007 and 2011. Subjects were classified as
      having reversible (>=10% increase to a final LV ejection fraction of >=50%) or
      irreversible (<=10% increase or final LV ejection fraction <50%) LV dysfunction
      on the basis of echocardiographic follow-up. A reference group with >=10% VPDs
      but normal LV function was identified. RESULTS: One hundred fourteen patients
      with >=10% VPDs were identified; 66 had preserved and 48 had impaired LV
      function. Over a median follow-up of 10.6 months, 24 of 48 were classified as
      reversible and 13 of 48 as irreversible and 11 of 44 were excluded. There was a
      gradient of VPD QRS duration between the control, reversible, and irreversible
      groups (mean VPD QRS 135, 158, and 173 ms, respectively; P < .001). This gradient
      persisted even for the same site of origin. In multivariate analysis, the only
      independent predictor of irreversible LV function was VPD QRS duration (odds
      ratio 5.07 [95% confidence interval 1.22-21.01] per 10-ms increase). CONCLUSION:
      In patients with LV dysfunction and frequent VPDs, we identified VPD QRS duration
      as the only independent predictor for the recovery of LV function after ablation.
      This suggests that VPD QRS duration may be a marker for the severity of
      underlying substrate abnormality.

PMID- 22640895
TI  - Synaptic localization of acylpeptide hydrolase in adult rat telencephalon.
AB  - Acylpeptide hydrolase (ACPH), a serine protease present in the central nervous
      system (CNS), is believed to have a function in modulating synaptic plasticity,
      cleavage of beta amyloid peptide and degradation of aggregated oxidized proteins.
      In this report, we demonstrate for the first time the presence of ACPH in the
      synapse and its preferential localization at the pre-synaptic side. We isolated
      subcellular fractions from the rat telencephalon enriched in pre- versus post
      synaptic components by using differential centrifugation steps to evaluate ACPH
      catalytic activity and expression level. Relative ACPH levels were determined by
      Western blot techniques while antibodies against synaptophysin and PSD-95 were
      used as positive pre- and post-synaptic markers, respectively. Our results show
      that ACPH protein levels are significantly increased at the synapse, which
      correlates with a 56% increase in ACPH activity. Furthermore, Western blot
      experiments show that ACPH is preferentially located at the pre-synaptic side and
      this is consistent with the increase of its enzymatic activity in fractions
      enriched in pre-synaptic components. These results give new insights regarding
      the localization and a putative role of ACPH in the CNS.

PMID- 22640896
TI  - Effect of SOX10 gene polymorphism on early onset schizophrenia in Chinese Han
      population.
AB  - Schizophrenia is one of highly heritable psychiatric disorders. Patients with
      early onset schizophrenia tend to have a greater genetic loading and may be an
      attractive subpopulation for genetics studies. A single nucleotide polymorphism
      (SNP) rs139887 in sex-determining region Y-box 10 (SOX10), a candidate gene for
      schizophrenia, was suggested to be associated with schizophrenia although
      inconsistent results had been reported. The aim of this study was to evaluate the
      association between SOX10 rs139887 polymorphism and schizophrenia using an early
      onset sample in the Chinese Han population. A total of 321 schizophrenic patients
      with onset before age 18 and 400 healthy controls were recruited for association
      study. In addition, two populations involved in three studies were selected for
      meta-analysis to determine the effect of rs139887 on schizophrenia. Our
      association study results showed that the allele and genotype frequencies were
      significantly different between schizophrenic patients and controls (P=0.013 and
      P=0.034, respectively). Interestingly, a significant association in allele and
      genotype frequencies were found in male patients (P=0.017 and P=0.045,
      respectively), but not female patients. Moreover, the C/C genotype had a
      significant association with an earlier age of onset in male schizophrenic
      patients (Kaplan-Meier log-rank test P=0.029), but not in female patients (Kaplan
      Meier log-rank test P=0.876). The meta-analysis result showed the same C allele
      was significantly associated with schizophrenia (P=0.007). In conclusion, the
      SOX10 rs139887 polymorphism was related to the development of schizophrenia in a
      gender-specific manner, and may be a significant genetic marker for managing
      subgroups and etiological clues in schizophrenia.

PMID- 22640897
TI  - The influence of DHEA pretreatment on prepulse inhibition and the HPA-axis stress
      response in rat offspring exposed prenatally to polyriboinosinic
      polyribocytidylic-acid (PIC).
AB  - Prenatal exposure to maternal infection may be associated with the development of
      neurodevelopmental disorders as well as increased susceptibility to the
      development of schizophrenia. Prenatal administration of polyriboinosinic
      polyribocytidilic-acid, mimicking RNA virus exposure, has been shown to induce
      schizophrenia-like behavioral, neurochemical and neuorophysiological
      abnormalities in rodent offspring. In the present study PIC prenatal
      administration at gestation day 15 was associated with alterations in the
      acoustic-startle-response/prepulse-inhibition [ASR/PPI] and the HPA-axis stress
      response in rat offspring on day 90. We show that pretreatment with
      dehydroepiandrosterone (DHEA) reverses PIC-related ASR/PPI disruption in female
      rats and normalizes HPA-axis stress response in a united group of male and female
      rats. Further research in both animal and human studies is recommended in order
      to confirm these preliminary findings and their application to the understanding
      and management of schizophrenia and related conditions.

PMID- 22640898
TI  - Effect of bite-raised condition on the hippocampal cholinergic system of aged
      SAMP8 mice.
AB  - Occlusal disharmony induces chronic stress, which results in learning deficits in
      association with the morphologic changes in the hippocampus, e.g., neuronal
      degeneration and increased hypertrophied glial fibrillary acidic protein-positive
      cells. To investigate the mechanisms underlying impaired hippocampal function
      resulting from occlusal disharmony, we examined the effects of the bite-raised
      condition on the septohippocampal cholinergic system by assessing acetylcholine
      release in the hippocampus and choline acetyltransferase immunoreactivity in the
      medial septal nucleus in aged SAMP8 mice that underwent the bite raising
      procedure. Aged bite-raised mice showed decreased acetylcholine release in the
      hippocampus and a reduced number of choline acetyltransferase-immunopositive
      neurons in the medial septal nucleus compared to age-matched control mice. These
      findings suggest that the bite-raised condition in aged SAMP8 mice enhances the
      age-related decline in the septohippocampal cholinergic system, leading to
      impaired learning.

PMID- 22640900
TI  - Self-directed learning readiness and learning styles among Saudi undergraduate
      nursing students.
AB  - BACKGROUND: Self-directed learning has become a focus for nursing education in
      the past few decades due to the complexity and changes in nursing profession
      development. On the other hand, the Kolb's learning style could identify
      student's preference for perceiving and processing information. OBJECTIVES: This
      study was performed to determine Saudi nursing students' readiness for self
      directed learning; to identify their learning styles and to find out the relation
      between these two concepts. DESIGN: Cross-sectional descriptive study. SETTINGS:
      Nursing department of faculty of Applied Medical Sciences, Al-Jouf University,
      Saudi Arabia. PARTICIPANTS: Two hundred and seventy-five undergraduate Saudi
      nursing students. METHODS: Data was collected using self-administered
      questionnaires covering the demographic features of students, Fisher's self
      directed learning readiness (SDLR) scale, and the Kolb's learning styles
      inventory. RESULTS: The mean scores of self-management, desire for learning, self
      control and the overall SDLR were 51.3 +/- 5.9, 48.4 +/- 5.5, 59.9 +/- 6.7, and
      159.6 +/- 13.8; respectively. About 77% (211) of students have high level of
      SDLR. The percentages of converger, diverger, assimilator and accommodator
      learning styles are 35.6%, 25.8%, 25.55% and 13.1%; respectively. The mean score
      of self-management, desire for learning, self-control and overall SDLR scale did
      not vary with any of the studied variables. There is no association between the
      level of SDLR and the learning styles. CONCLUSIONS: The high level of SDLR and
      the dominant converger learning style among undergraduate nursing students will
      have a positive implication for their education and post-employment continuing
      nursing education.

PMID- 22640899
TI  - The ER chaperone GRP78 is associated with the severity of cerulein-induced
      pancreatic inflammation via regulating apoptosis of pancreatic acinar cells.
AB  - BACKGROUND/AIMS: To study the potential role of the 78kDa glucose regulated
      protein (GRP78) in the pathogenesis of acute pancreatitis (AP) in vitro.
      METHODOLOGY: AR42J cells were stimulated by cerulein or cerulein plus
      lipoplysaccharide (LPS). The severity of pancreatic inflammation was evaluated by
      amylase, lipase, TNF-a, and IL-6. Apoptosis was determined by flow cytometry; the
      expressions of apoptotic genes, GRP78 and the downstream molecules were
      determined by real-time quantitative PCR and Western blot. RESULTS: After
      cerulein stimulation, the levels of amylase, lipase, TNF-a and IL-6 were all
      increased, with a more pronounced increase after cerulein plus LPS stimulation.
      Apoptosis was different in two cell models, high apoptosis in cerulein group;
      whereas cerulein plus LPS induced relatively less apoptosis. Apoptotic gene
      expressions revealed more pronounced increase in the cerulein group than those in
      cerulein plus LPS group. The expressions of GRP78 and downstream molecules were
      different in two cell models. GRP78 expression was down-regulated in cerulein
      group and upregulated in cerulein plus LPS group. CONCLUSIONS: GRP78 expression
      was associated with apoptosis and the severity of cerulein-induced pancreatic
      inflammation, indicating that GRP78 might prevent apoptosis in pancreatic acinar
      cells thereby deteriorating the severity of AP.

PMID- 22640901
TI  - Optimization and correlation of HPLC-ELSD and HPLC-MS/MS methods for
      identification and characterization of sophorolipids.
AB  - High-performance liquid chromatography (HPLC) with evaporative light scattering
      detection (ELSD) and HPLC with electrospray ionization tandem mass spectrometry
      (HPLC-ESI-MS/MS) methods were implemented and optimized to separate and identify
      sophorolipids (SLs) produced by Rhodotorula bogoriensis and Starmerella
      bombicola. SLs are carbohydrate-based amphiphilic biosurfactants with increased
      interest in pharmaceutical and environmental areas. Rhodotorula bogoriensis and
      Starmerella bombicola are mainly producers of respectively C22, and C16 and C18
      SLs. Mass fragmentation patterns of SLs produced by both yeasts were investigated
      by HPLC-ESI-MS/MS in the positive mode for [M+Na]+. Based on the established
      fragmentation pattern, SLs produced by both yeasts were identified and
      characterized. A correlation between HPLC-ELSD and HPLC- ESI-MS/MS methods was
      established and made possible the identification of SLs by the HPLC-ELSD
      technique. TLC is a common tool for the analysis of SLs mixtures. In this work,
      TLC scrapped bands were analysed by HPLC-ELSD and HPLC-MS allowing the
      correlation between R(F) values and the identification of sophorolipids by this
      technique. Identification of monoacetylated and diacetylated C24:0 hydroxy fatty
      acids sophorolipids produced by Rhodotorula bogoriensis was for the first time
      accomplished with this study. Although present in lower quantity these longer
      chain SLs can assume special importance regarding their biological activity and
      surface active properties.

PMID- 22640902
TI  - A brief review of Susac syndrome.
AB  - Susac syndrome was named after J.O. Susac who first described the syndrome in
      1979. It is characterized by the clinical triad of encephalopathy, branch retinal
      artery occlusion, and sensorineural hearing loss. It mainly occurs in young
      women. This underdiagnosed disease needs to be considered in the differential
      diagnosis of a broad variety of disorders. In Susac syndrome, autoimmune
      processes leading to damage and inflammation-related occlusion of the
      microvessels in brain, retina, and inner ear are thought to play a causal role.
      The diagnosis is based primarily on the clinical presentation, the documentation
      of branch retinal artery occlusion by fluorescence angiography, and
      characteristic findings on cerebral MRI, that help in distinguishing Susac
      syndrome from other inflammatory entities, like multiple sclerosis.
      Antiendothelial cell antibodies could be detected in some patients. Patients are
      successfully treated with immunosuppression, however, the best regimen still
      needs to be defined. As a result of the rarity of the disease, controlled
      therapeutic trials are missing so far. In this review, we want to demonstrate the
      clinical features, natural history, treatment, and clinical course of Susac
      syndrome, illustrated by a typical case history.

PMID- 22640903
TI  - Early detection of familial Creutzfeldt-Jakob disease on diffusion-weighted
      imaging before symptom onset.
AB  - Familial Creutzfeldt-Jakob disease (CJD) with V180I shows different clinical
      characteristics from classical CJD and is difficult to diagnose in the early
      stage. We report a CJD180 patient in whom results of diffusion-weighted imaging
      (DWI) led us to suspect CJD before symptoms started. A 68-year-old woman
      presented to our hospital with headache and nausea and underwent magnetic
      resonance imaging. DWI showed cortical hyperintensity. Three months later,
      cognitive function started to decline and CJD180 was diagnosed following genetic
      examination. In the early stage, ADC values were not decreased and single
      positron emission computed tomography demonstrated a decreased pattern like
      Alzheimer disease.

PMID- 22640904
TI  - Layout-aware text extraction from full-text PDF of scientific articles.
AB  - BACKGROUND: The Portable Document Format (PDF) is the most commonly used file
      format for online scientific publications. The absence of effective means to
      extract text from these PDF files in a layout-aware manner presents a significant
      challenge for developers of biomedical text mining or biocuration informatics
      systems that use published literature as an information source. In this paper we
      introduce the 'Layout-Aware PDF Text Extraction' (LA-PDFText) system to
      facilitate accurate extraction of text from PDF files of research articles for
      use in text mining applications. RESULTS: Our paper describes the construction
      and performance of an open source system that extracts text blocks from PDF
      formatted full-text research articles and classifies them into logical units
      based on rules that characterize specific sections. The LA-PDFText system focuses
      only on the textual content of the research articles and is meant as a baseline
      for further experiments into more advanced extraction methods that handle multi
      modal content, such as images and graphs. The system works in a three-stage
      process: (1) Detecting contiguous text blocks using spatial layout processing to
      locate and identify blocks of contiguous text, (2) Classifying text blocks into
      rhetorical categories using a rule-based method and (3) Stitching classified text
      blocks together in the correct order resulting in the extraction of text from
      section-wise grouped blocks. We show that our system can identify text blocks and
      classify them into rhetorical categories with Precision1 = 0.96% Recall = 0.89%
      and F1 = 0.91%. We also present an evaluation of the accuracy of the block
      detection algorithm used in step 2. Additionally, we have compared the accuracy
      of the text extracted by LA-PDFText to the text from the Open Access subset of
      PubMed Central. We then compared this accuracy with that of the text extracted by
      the PDF2Text system, 2commonly used to extract text from PDF. Finally, we discuss
      preliminary error analysis for our system and identify further areas of
      improvement. CONCLUSIONS: LA-PDFText is an open-source tool for accurately
      extracting text from full-text scientific articles. The release of the system is
      available at http://code.google.com/p/lapdftext/.

PMID- 22640905
TI  - Nanomedicine for treatment of diabetes in an aging population: state-of-the-art
      and future developments.
AB  - Nowadays diabetes, especially type 2 diabetes (which is strongly related to the
      Western diet and life-style), has developed worldwide into an epidemic disease.
      Nanomedicine aims to provide novel tools for diagnosis, therapy and point-of-care
      management of patients. Several nanotechnological approaches were developed to
      improve life quality for patients with insulin-dependent diabetes. They
      facilitate blood glucose management by non-invasive glucose measurement as well
      as insulin administration mainly by delivering the fragile protein as protected
      and targeted formulation via nasal or oral route. In the present review the oral
      or nasal insulin delivery by polymeric nanoparticles is discussed with focus on
      physiological change either related to the disease, diabetes or age-related
      metabolic variations influencing insulin release and bioavailability. One
      critical point is that new generations of targeted nanoparticle based drugs are
      developed and optimized for certain metabolic conditions. These conditions may
      change with age or disease. The influence of age-related factors such as
      immaturity in very young age, metabolic and physiologic changes in old age or
      insufficient animal models are still under-investigated not only in nanomedicine
      but also generally in pharmacology. Summarizing it can be noted that the
      bioavailability of insulin administered via routes others than subcutaneously is
      comparably low (max. 60%). Moreover factors like changed gut permeability as
      described for diabetes type 1 or other metabolic peculiarities such as insulin
      resistance in case of type 2 diabetes also play a role in affecting the
      development of novel nanoparticulated drug preparations and can be responsible
      for unsuccessful translation of promising animal results into human therapy. In
      future insulin nanoparticle development for diabetes must consider not only
      requirements imposed by the drug but also metabolic changes inflicted by disease
      or by age. Moreover new approaches are required for prevention of the disease.

PMID- 22640906
TI  - Nanomedicine for the prevention, treatment and imaging of atherosclerosis.
AB  - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in
      developed countries, with an increasing prevalence due to an aging population.
      The pathology underpinning CVD is atherosclerosis, a chronic inflammatory state
      involving the arterial wall. Accumulation of low density lipoprotein (LDL) laden
      macrophages in the arterial wall and their subsequent transformation into foam
      cells lead to atherosclerotic plaque formation. Progression of atherosclerotic
      lesions may gradually lead to plaque related complications and clinically
      manifest as acute vascular syndromes including acute myocardial or cerebral
      ischemia. Nanotechnology offers emerging therapeutic strategies, which may have
      advantage overclassical treatments for atherosclerosis. In this review, we
      present the potential applications of nanotechnology toward prevention,
      identification and treatment of atherosclerosis.

PMID- 22640907
TI  - Magnetic nanovectors for drug delivery.
AB  - Nanotechnology holds the promise of novel and more effective treatments for
      vexing human health issues. Among these are the use of nanoparticle platforms for
      site-specific delivery of therapeutics to tumors, both by passive and active
      mechanisms; the latter includes magnetic vectoring of magnetically responsive
      nanoparticles (MNP) that are functionalized to carry a drug payload that is
      released at the tumor. The conceptual basis, which actually dates back a number
      of decades, resides in physical (magnetic) enhancement, with magnetic field
      gradients aligned non-parallel to the direction of flow in the tumor vasculature,
      of existing passive mechanisms for extravasation and accumulation of MNP in the
      tumor interstitial fluid, followed by MNP internalization. In this review, we
      will assess the most recent developments and current status of this approach,
      considering MNP that are composed of one or more of the three elements that are
      ferromagnetic at physiological temperature: nickel, cobalt and iron. The effects
      on cellular functions in vitro, the ability to successfully vector the platform
      in vivo, the anti-tumor effects of such localized nano-vectors, and any
      associated toxicities for these MNP will be presented. The merits and
      shortcomings of nanomaterials made of each of the three elements will be
      highlighted, and a roadmap for moving this long-established approach forward to
      clinical evaluation will be put forth.

PMID- 22640908
TI  - Nanoparticle delivery for metastatic breast cancer.
AB  - Breast cancer represents a major ongoing public health problem as the most common
      non-cutaneous malignancy among U.S. women. While significant progress has been
      made in improving loco-regional treatments for breast cancer, relatively little
      progress has been made in diagnosing and treating patients with metastatic breast
      cancer. At present there are limited curative options for patients with breast
      cancer metastatic beyond regional nodes. Emerging nanotechnologies promise new
      approaches to early detection and treatment of metastatic breast cancer.
      Fulfilling the promise of nanotechnologies for patients with metastatic breast
      cancer will require delivery of nanomaterials to sites of metastatic disease.
      Future translational approaches will rely on an ever increasing understanding of
      the biology of breast cancer subtypes and their metastases. These important
      concepts will be highlighted and elucidated in this manuscript.

PMID- 22640909
TI  - Nanoparticle delivery for transdermal HRT.
AB  - Nanomedicine is an emerging technology and the first nano-engineered medical
      products have come to light in the last decade. Transdermal drug delivery has
      significant advantages compared to other routes of drug administration.
      Nanoparticles unique physical and chemical properties enable transport of
      substances directly into the skin. The objective of this paper is to review
      different aspects of nanoparticle delivery, generally, and discuss its current
      use for transdermal hormone therapy. Transdermal estrogen therapy remains the
      most effective treatment for bothersome menopausal symptoms, particularly in
      those women for whom the potential adverse effects associated with "first pass"
      hepatic metabolism are to be avoided. Available alternatives for transdermal
      estrogen delivery include patches, gels, sprays and lotions. Other non-oral
      therapies which likewise avoid "first pass" hepatic metabolism include:
      subcutaneous implants and vaginal rings. Some of the transdermal products are
      associated with mild adverse skin effects such as redness and irritation, but
      more severe and bothersome consequences include blistering and tattooing. Even
      the mild adverse skin effects are frequently cited as reasons for
      discontinuation. Micellar nanoparticle estradiol emulsion (MNPEE) is a lotion
      like therapy which constitutes an alternative transdermal delivery system not
      requiring the permeation enhancers or temporary skin digestion, both of which
      increase the possibility of irritation. MNPEE's advantages include low
      fluctuation of plasma estradiol concentrations, infrequent skin related adverse
      effects, and pleasant cosmetic-like moisturizing properties. The efficacy of
      MNPEE for management of menopausal vasomotor symptoms has been demonstrated in a
      randomized placebo controlled trial,(1) and the product is FDA approved for
      management of moderate to severe vasomotor symptoms. None of the observed adverse
      effects in the MNPEE group were statistically different from the placebo
      group.(1) Studies addressing inadvertent transference of estradiol to the male
      partners of menopausal women using this delivery technology have demonstrated
      small, but real amounts of transference, which do not exceed the normal
      physiological male estradiol range. MNPEE is safe and effective for treatment of
      vasomotor symptoms and represents the commercial validation of nanoparticle
      technology for transdermal delivery of estrogen therapy (ET) for postmenopausal
      women with vasomotor symptoms.

PMID- 22640910
TI  - Nanotechnology for neurodegenerative disorders.
AB  - The efficacy, cellular uptake and specific transport of drugs and/or imaging
      agents to target organs, tissues and cells are common issues in the diagnosis and
      treatment of different disorders. In the case of neurodegenerative diseases, they
      represent complex problems, since brain targeting remains a still unsolved
      challenge in pharmacology, due to the presence of the blood-brain barrier, a
      tightly packed layer of endothelial cells that prevents unwanted substances to
      enter the brain. Engineered nanomaterials, objects with dimensions of 1-100 nm,
      are providing interesting biomedical tools potentially able to solve these
      problems, thanks to their physico-chemical features and to the possibility of
      multi-functionalization, allowing to confer them different features at the same
      time, including the ability to cross the blood-brain barrier. This review focuses
      on the state-of-the-art of nanomaterials suitable for therapy and diagnostic
      imaging of the most common neurodegenerative disorders, as well as for
      neuroprotection and neuronal tissue regeneration. Finally, their potential
      neurotoxicity is discussed, and future nanotechnological approaches are
      described.

PMID- 22640911
TI  - Nanoparticle therapeutics for prostate cancer treatment.
AB  - The application of nanotechnology in medicine is offering many exciting
      possibilities in healthcare. Engineered nanoparticles have the potential to
      revolutionize the diagnosis and the therapy of several diseases, particularly by
      targeted delivery of anticancer drugs and imaging contrast agents. Prostate
      cancer, the second most common cancer in men, represents one of the major
      epidemiological problems, especially for patients in the advanced age. There is a
      substantial interest in developing therapeutic options for treatment of prostate
      cancer based on use of nanodevices, to overcome the lack of specificity of
      conventional chemotherapeutic agents as well as for the early detection of
      precancerous and malignant lesions. Herein, we highlight on the recent
      development of nanotechnology strategies adopted for the management of prostate
      cancer. In particular, the combination of targeted and controlled-release polymer
      nanotechnologies has recently resulted in the clinical development of BIND-014, a
      promising targeted Docetaxel-loaded nanoprototype, which can be validated for use
      in the prostate cancer therapy. However, several limitations facing nanoparticle
      delivery to solid tumours, such as heterogeneity of intratumoural barriers and
      vasculature, cytotoxicity and/or hypersensitivity reactions to currently
      available cancer nanomedicines, and the difficult in developing targeted
      nanoparticles with optimal biophysicochemical properties, should be still
      addressed for a successful tumour eradication.

PMID- 22640913
TI  - Left ventricular strain and peak systolic velocity: responses to controlled
      changes in load and contractility, explored in a porcine model.
AB  - BACKGROUND: Tissue velocity echocardiography is increasingly used to evaluate
      global and regional cardiac function. Previous studies have suggested that the
      quantitative measurements obtained during ejection are reliable indices of
      contractility, though their load-sensitivity has been studied in different
      settings, but still remains a matter of controversy. We sought to characterize
      the effects of acute load change (both preload and afterload) and change in
      inotropic state on peak systolic velocity and strain as a measure of LV
      contractility. METHODS: Thirteen anesthetized juvenile pigs were studied, using
      direct measurement of left ventricular pressure and volume and transthoracic
      echocardiography. Transient inflation of a vena cava balloon catheter produced
      controlled load alterations. At least eight consecutive beats in the sequence
      were analyzed with tissue velocity echocardiography during the load alteration
      and analyzed for change in peak systolic velocities and strain during same
      contractile status with a controlled load alteration. Two pharmacological
      inotropic interventions were also included to generate several myocardial
      contractile conditions in each animal. RESULTS: Peak systolic velocities
      reflected the drug-induced changes in contractility in both radial and
      longitudinal axis. During the acute load change, the peak systolic velocities
      remain stable when derived from signal in the longitudinal axis and from the
      radial axis. The peak systolic velocity parameter demonstrated no strong relation
      to either load or inotropic intervention, that is, it remained unchanged when
      load was systematically and progressively varied (peak systolic velocity,
      longitudinal axis, control group beat 1-5.72 +/- 1.36 with beat 8-6.49 +/- 1.28
      cm/sec, 95% confidence interval), with the single exception of the negative
      inotropic intervention group where peak systolic velocity decreased a small
      amount during load reduction (beat 1-3.98 +/- 0.92 with beat 8-2.72 +/- 0.89
      cm/sec). Systolic strain, however, showed a clear degree of load-dependence.
      CONCLUSIONS: Peak systolic velocity appears to be load-independent as tested by
      beat-to-beat load reduction, while peak systolic strain appears to be load
      dependent in this model. Peak systolic velocity, in a controlled experimental
      model where successive beats during load alteration are assessed, has a strong
      relation to contractility. Peak systolic velocity, but not peak strain rate, is
      largely independent of load, in this model. More study is needed to confirm this
      finding in the clinical setting.

PMID- 22640912
TI  - Nanomedicines for chronic non-infectious arthritis: the clinician's perspective.
AB  - Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent chronic health
      conditions. However, despite recent advances in medical therapeutics, their
      treatment still represents an unmet medical need because of safety and efficacy
      concerns with currently prescribed drugs. Accordingly, there is an urgent need to
      develop and test new drugs for RA and OA that selectively target inflamed joints
      thereby mitigating damage to healthy tissues. Conceivably, biocompatible,
      biodegradable, disease-modifying antirheumatic nanomedicines (DMARNs) could
      represent a promising therapeutic approach for RA and OA. To this end, the unique
      physicochemical properties of drug-loaded nanocarriers coupled with
      pathophysiological characteristics of inflamed joints amplify bioavailability and
      bioactivity of DMARNs and promote their selective targeting to inflamed joints.
      This, in turn, minimizes the amount of drug required to control articular
      inflammation and circumvents collateral damage to healthy tissues. Thus,
      nanomedicine could provide selective control both in space and time of the
      inflammatory process in affected joints. However, bringing safe and efficacious
      DMARNs for RA and OA to the marketplace is challenging because regulatory
      agencies have no official definition of nanotechnology, and rules and definitions
      for nanomedicines are still being developed. Although existing toxicology tests
      may be adequate for most DMARNs, as new toxicity risks and adverse health effects
      derived from novel nanomaterials with intended use in humans are identified,
      additional toxicology tests would be required. Hence, we propose that detailed
      pre-clinical in vivo safety assessment of promising DMARNs leads for RA and OA,
      including risks to the general population, must be conducted before clinical
      trials begin.

PMID- 22640914
TI  - Characterization of somatostatin receptor 2 and 5 expression in operable
      hepatocellular carcinomas.
AB  - BACKGROUND/AIMS: Somatostatin analog improves survival in patients with advanced
      hepatocellular carcinoma by interacting with its specific receptor 2 and 5.
      However, expression of somatostatin receptor (SSTR) in operable HCC is still
      unclear. In this study, we analyzed the expression of SSTR-2 and -5 in HBV
      related HCC and compared its clinicopathological features and follow-up data.
      METHODOLOGY: Seventy six patients with HCC were enrolled. SSTR-2 and -5
      expression was investigated by QPCR and immunohistochemistry in all the samples.
      Furthermore, the association between gene expression and survival was analyzed.
      RESULTS: Compared to surrounding cirrhotic tissues, mRNA levels of SSTR-2 and -5
      in HCCs were significantly reduced. Seventy six HCC patients were divided into
      two groups according to SSTR-2 and 5 expression profiles. Both groups were well
      balanced with respect to baseline characteristics. According to univariate
      analysis, the mean survival time was longer in the HIGH SSTR-2/5 expression
      group. Multivariate Cox analysis showed that tumor expression level of SSTR-2 can
      be used as an independent prognostic marker of HCC as well as tumor TNM stage.
      CONCLUSIONS: Downregulation of SSTR transcription may result in loss of a tumor
      suppressive. Characterization of SSTR expression can be used as a useful
      parameter to evaluate the prognosis of HCC.

PMID- 22640915
TI  - Prophylactic anticoagulation following splenectomy in cirrhotic patients.
AB  - BACKGROUND/AIMS: The aim of the study is to address the impact of prophylactic
      anticoagulation on the incidence of PVT in cirrhotic patients compared with no
      prophylactic anticoagulation after splenectomy. METHODOLOGY: Randomized
      controlled trials (RCTs) comparing prophylactic anticoagulation and no
      prophylactic anticoagulation after splenectomy were included by a systematic
      literature search. Two authors independently assessed the trials for inclusion
      and extracted the data. RESULTS: A total of 1406 studies were searched and none
      met our inclusion criteria. CONCLUSIONS: Most current studies were not
      prospective control trials based on small sample sizes and single center
      experiences. Therefore, it is hard to draw the conclusion that prophylactic
      anticoagulation following splenectomy should be recommended in cirrhotic
      patients. More attention to the problem Is required and the administration of
      routine postoperative anticoagulation needs to be standardized.

PMID- 22640916
TI  - Using a small-for-size graft might attribute to the future use of left-lobe
      living graft in adult to adult living donor liver transplantation.
AB  - BACKGROUND/AIMS: Adult to adult living donor liver transplantation (AALDLT) is
      performed worldwide. The aim of this study was to evaluate using a graft with
      graft to body weight ratio (GBWR) less than 0.8 in right-lobe AALDLT recipients.
      METHODOLOGY: Clinical data of 127 patients who had right-lobe AALDLT from January
      2002 to November 2009 were retrospectively analyzed. Patients were divided into
      two groups according to GBWR (group A: 0.6 <= GBWR < 0.8, group B: GBWR >= 0.8).
      Preoperative characteristics, postoperative complications graded by the Clavien
      score and patient survival time were recorded and analyzed. RESULTS: GBWR between
      the two groups were significantly different (0.67 +/- 0.05 vs. 0.97 +/- 0.17, p =
      0.000). There was no significant difference in preoperative demographic data as
      well as postoperative liver function data. Complication rate, median ICU stay and
      small-for-size syndrome incidence were similar in both groups. In univariate
      analysis, only MELD emerged as independent risk factor for small-for-size
      syndrome (p = 0.045). Patient survival was similar in both groups at 1, 3 and 5
      years as well. CONCLUSIONS: Using a GBWR of less than 0.8 is safe in selected
      recipients. To some extent, this result may attribute to the wide use of left
      lobe living graft in AALDLT in future.

PMID- 22640917
TI  - [Fibrosarcoma in children and adolescents: different entities for the same name].
AB  - Fibrosarcomas (FS) are rare malignant tumors in pediatrics, classified in the
      heterogeneous non-rhabdomyosarcomas group of malignant mesenchymal tumors.
      Infantile FS are found typically in children less than 2 years of age, and
      include congenital FS usually occurring in infants in the first 3 months of life.
      Histological diagnosis can be difficult; and confirmed with detection by
      molecular biology of the ETV6-NTRK3 fusion protein. FS is most often a localized
      disease at diagnosis, with involvement of an extremity. The management of these
      patients must be multidisciplinary, to define the different phases of treatment
      and avoid mutilating surgery. Cellular or atypical mesoblastic nephroma (MN) is a
      subtype of malignant pediatric renal tumors, most often present in children of
      less than 3 months. Histopathological characteristics of the cellular MN are very
      close to the congenital FS due to a fusion transcript common to both diseases.
      Treatment schedule is defined by initial local stage of the disease. FS called
      "adult-type" found exceptionally in childhood occur most often after 10 years
      old. Adult FS differ from infantile FS in their clinical presentation because of
      a strong local aggressiveness and problematic appearance of metastasis in 50% of
      cases, sometimes late. These three diseases present therefore histological
      similarities. Both have a common name but different clinical presentation and
      outcome: infantile FS and adult FS. Two have different names and initial location
      but similar histology, chromosomal rearrangement, sensitivity to chemotherapy and
      outcome: the congenital FS and cellular mesoblatic nephroma. Authors present a
      review of the literature of these entities.

PMID- 22640918
TI  - Spatial and temporal dynamics of size-structured photosynthetic parameters (PAM)
      and primary production (13C) of pico- and nano-phytoplankton in an atoll lagoon.
AB  - Atoll lagoons display a high diversity of trophic states due mainly to their
      specific geomorphology, and probably to their level and mode of human
      exploitation. We investigated the functioning of the Ahe atoll lagoon, utilized
      for pearl oyster farming, through estimations of photosynthetic parameters (pulse
      amplitude modulation fluorometry) and primary production ((13)C incorporation)
      measurements of the size structured phytoplankton biomass (<2 MUm and >2 MUm).
      Spatial and temporal scales of variability were surveyed during four seasons,
      over 16 months, at four sites within the lagoon. While primary production (P) was
      dominated by the picophytoplankton, its biomass specific primary productivity
      (P(B)) was lower than in other atoll lagoons. The variables size fraction of the
      phytoplankton, water temperature, season, the interaction term station*fraction
      and site, explained significantly the variance of the data set using redundancy
      analysis. No significant trends over depth were observed in the range of 0-20 m.
      A clear spatial pattern was found which was persistent over the seasons: south
      and north sites were different from the two central stations for most of the
      measured variables. This pattern could possibly be explained by the existence of
      water cells showing different water residence time within the lagoon.
      Photoacclimation strategies of the two size fractions differed through their
      light saturation coefficient (higher for picophytoplankton), but not through
      their maximum photosynthetic capacity (ETR(max)). Positive linear relationships
      between photosynthetic parameters indicated that their dynamic was independent of
      light availability in this ecosystem, but most probably dependent on nutrient
      availability and/or rapid changes in the community structure. Spatial and
      temporal patterns of the measured processes are then further discussed in the
      context of nutrient availability and the possible role of cultured oysters in
      nutrient recycling.

PMID- 22640919
TI  - Comparative cyto-genotoxicity assessment of functionalized and pristine
      multiwalled carbon nanotubes on human lung epithelial cells.
AB  - Chemical functionalization extends CNT applications conferring them new
      functions, but could modify their toxicity. We compared cytotoxicity and
      genotoxic/oxidative effects of -OH functionalized and pristine MWCNTs to
      evaluated the influence of the functionalization exposing A549 cells to 1
      40MUg/ml of both MWCNTs for 2, 4 and 24h. Cytotoxicity was evaluated by MTT and
      LDH tests and apoptosis induction, direct/oxidative DNA damage by Fpg-modified
      comet assay. After 24h we found viability reduction significant at 20 and
      40MUg/ml for both the MWCNTs with a detectable viability reduction already at
      lower concentrations for MWCNTs. A significant LDH release was found only for
      MWCNTs. Significant apoptosis induction was found from 10MUg/ml of MWCNT-OH. A
      concentration-dependent increase of direct DNA damage, significant at 40MUg/ml of
      MWCNTs and beginning from 5MUg/ml of MWCNT-OH was detected at all exposure times.
      Oxidative DNA damage was not observed for both CNTs. The results indicate a
      different cytotoxic mechanism, by membrane damage for MWCNTs and apoptosis for
      MWCNT-OH, that could be explained by a different cellular uptake. Moreover, we
      found an earlier genotoxic effect for MWCNT-OH. The findings suggest that further
      studies on functionalized CNTs are necessary before using them in several
      applications particularly in biomedical field.

PMID- 22640920
TI  - Bovine liver slices: A multifunctional in vitro model to study the prohormone
      dehydroepiandrosterone (DHEA).
AB  - Biotransformation of inactive prohormones like dehydroepiandrosterone (DHEA) can
      lead to the formation of potent androgens and subsequent androgenic responses in
      target tissues. In the present study, precision-cut bovine liver slices were used
      to study the effects of DHEA on the metabolite, transcript and androgenic
      activity level. Bovine liver slices were exposed for 6h to various concentrations
      of DHEA. Changes in androgenic activity of the DHEA containing cell culture media
      were measured using a yeast androgen bioassay and metabolites were identified
      using ultra performance liquid chromatography time-of-flight mass spectrometry
      (UPLC-TOFMS), while gene expression in the DHEA-treated liver slices was examined
      using bovine microarrays and compared with the profile as obtained with 17beta
      testosterone (17beta-T). An increase in androgenic activity was observed in the
      bioassay upon testing of samples from incubations of DHEA with liver slices and
      the formation of 4-androstenedione (4-AD), 5-androstene-3beta,17beta-diol, 17beta
      T, 7alpha-hydroxy-DHEA, 7-keto-DHEA and 17alpha-T could be confirmed by UPLC
      TOFMS analysis. Exposure of liver slices to DHEA and the strong androgen 17beta-T
      resulted in the identification of significantly up- and down-regulated genes and
      revealed similar gene expression profiles for both compounds. The results
      indicate that DHEA itself is biologically not very active, but is rapidly
      converted by the liver slices into the more androgen active compounds 4-AD and
      17beta-T. Moreover, the present data highlight the multi-functionality of bovine
      liver slices as an in vitro bioactivation model, allowing the assessment of
      androgen activity or gene expression as effect-based endpoints for prohormone
      exposure.

PMID- 22640922
TI  - Activation of human neutrophils by Esenbeckia leiocarpa: comparison between the
      crude hydroalcoholic extract (CHE) and an alkaloid (Alk) fraction.
AB  - Esenbeckia leiocarpa, a wide spread native Brazilian tree, was reported recently
      to possess anti-inflammatory effects in vivo, but the mechanisms involved are
      still not fully understood and its role in neutrophils is poorly documented. The
      aim of this study was to compare the effects of a crude hydroalcoholic extract
      (CHE) and an alkaloid-enriched (Alk) fraction obtained from Esenbeckia leiocarpa
      bark on human neutrophils by investigating the effect of each fraction alone or
      in a mixture with classical neutrophil agonists. CHE inhibited intracellular
      reactive oxygen species (ROS) production but increased the extracellular
      superoxide (O2-) production, while Alk increased the former and also slightly
      increased O2- production. We found that CHE and Alk also induced phagocytosis
      accompanied by Syk activation, adhesion and degranulation. However, neither CHE
      nor Alk potentiated the effect of classical neutrophil agonists, namely the
      cytokines GM-CSF for phagocytosis and TNF-alpha for adhesion or N-formyl
      methionyl-leucyl-phenylalanine (fMLP) for degranulation. In addition, based on
      catalase treatment, CHE and Alk induced neutrophil apoptosis by a hydrogen
      peroxide (H2O2)-dependent mechanism. Since the elimination of apoptotic
      neutrophils by professional phagocytes is important for the resolution of
      inflammation, the ability of CHE and Alk to induce neutrophil apoptosis has to be
      considered as one possible mechanism associated with the anti-inflammatory
      activity of these fractions previously reported in vivo.

PMID- 22640921
TI  - A systems biology approach reveals common metastatic pathways in osteosarcoma.
AB  - BACKGROUND: Osteosarcoma (OS) is the most common malignant bone tumor in children
      and adolescents. The survival rate of patients with metastatic disease remains
      very dismal. Nevertheless, metastasis is a complex process and a single-level
      analysis is not likely to identify its key biological determinants. In this
      study, we used a systems biology approach to identify common metastatic pathways
      that are jointly supported by both mRNA and protein expression data in two
      distinct human metastatic OS models. RESULTS: mRNA expression microarray and N
      linked glycoproteomic analyses were performed on two commonly used isogenic pairs
      of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway
      analysis of the differentially regulated genes and glycoproteins separately
      revealed pathways associated to metastasis including cell cycle regulation,
      immune response, and epithelial-to-mesenchymal-transition. However, no common
      significant pathway was found at both genomic and proteomic levels between the
      two metastatic models, suggesting a very different biological nature of the cell
      lines. To address this issue, we used a topological significance analysis based
      on a "shortest-path" algorithm to identify topological nodes, which uncovered
      additional biological information with respect to the genomic and glycoproteomic
      profiles but remained hidden from the direct analyses. Pathway analysis of the
      significant topological nodes revealed a striking concordance between the models
      and identified significant common pathways, including "Cytoskeleton
      remodeling/TGF/WNT", "Cytoskeleton remodeling/Cytoskeleton remodeling", and "Cell
      adhesion/Chemokines and adhesion". Of these, the "Cytoskeleton
      remodeling/TGF/WNT" was the top ranked common pathway from the topological
      analysis of the genomic and proteomic profiles in the two metastatic models. The
      up-regulation of proteins in the "Cytoskeleton remodeling/TGF/WNT" pathway in the
      SaOS-2/LM7 and HOS/143B models was further validated using an orthogonal Reverse
      Phase Protein Array platform. CONCLUSIONS: In this study, we used a systems
      biology approach by integrating genomic and proteomic data to identify key and
      common metastatic mechanisms in OS. The use of the topological analysis revealed
      hidden biological pathways that are known to play critical roles in metastasis.
      Wnt signaling has been previously implicated in OS and other tumors, and
      inhibitors of Wnt signaling pathways are available for clinical testing. Further
      characterization of this common pathway and other topological pathways identified
      from this study may lead to a novel therapeutic strategy for the treatment of
      metastatic OS.

PMID- 22640925
TI  - [Quality of life of young women with early breast cancer and their partners:
      specific needs result in the necessity of development of specific questionnaires
      for the patient and the partner].
AB  - Purpose. To determine the feelings of young women with early breast cancer
      concomitantly with their partners at different treatment periods in order to
      create a specific quality of life (QOL) scale for this population. Materiel and
      methods. It was a prospective, multicentre, qualitative study, in patients
      younger than 45 years old at diagnosis and living with a partner for at least six
      months. Patients and partners were interviewed by a psychologist, from the
      diagnosis disclosure until follow up, using non-directing individual talks.
      Results. Sixty-nine couples were interviewed. Analyses of the interviews have
      highlighted the impact of disease on eight dimensions: psychological, physical,
      family, social, couple, sexuality, domestic, professional and economic
      dimensions. These impacts are mostly negative and are present in all periods and
      even after treatment for follow up. Discussion. A multidimensional profile of
      this specific population was established. A QOL scale dedicated to this
      population is being validated.

PMID- 22640924
TI  - Design and baseline data from the vanguard of the Comparison of Depression
      Interventions after Acute Coronary Syndrome (CODIACS) randomized controlled
      trial.
AB  - This paper describes the rationale and design of the vanguard for the Comparison
      of Depression Interventions after Acute Coronary Syndrome (CODIACS), a
      multicenter, randomized, controlled trial of a patient preference-based, stepped
      care protocol for persistent depressive symptoms after acute coronary syndrome
      (ACS). The overall aim of the vanguard phase was to determine whether the patient
      preference, stepped care protocol, which is based on the intervention used in the
      recent Coronary Psychosocial Evaluation Studies (COPES) trial, was feasible in
      patients with recent ACS who were recruited from 5 geographically diverse sites.
      Innovative design features of this trial include randomization to either initial
      patient-preference of treatment or to a referred care arm in which the primary
      care provider decided upon care. Additionally, delivery of psychotherapy was
      accomplished by telephone, or webcam, depending upon patient preference. The
      vanguard phase provides estimates of eligibility and screening/enrollment ratios,
      patient acceptance of screening, and retention. In this report, we describe the
      innovative features and the baseline results of the vanguard phase of CODIACS.
      The data from this vanguard study will be used to finalize planning for a large,
      phase III clinical trial designed to evaluate the effect of treatment on
      depressive symptoms, coronary events, and death.

PMID- 22640923
TI  - A Mediterranean dietary intervention in persons at high risk of colon cancer:
      recruitment and retention to an intensive study requiring biopsies.
AB  - This study recruited persons at increased risk of colon cancer to an intensive
      dietary intervention study that required biopsies of the colon by flexible
      sigmoidoscopy at baseline and after six months of intervention. A total of 1314
      individuals contacted the study, and only 16 individuals indicated that the
      sigmoidoscopy procedure was an obstacle to study participation. A total of 270
      individuals completed a screening visit and signed a screening consent form.
      Inquiries about the study tended to be fewer in the winter and late summer.
      Failure to return food records was the most common reason for exclusion. Dietary
      recall at enrollment indicated that subjects were consuming significantly more
      vegetables, lower sodium and a lower glycemic load on the day before starting the
      study vs. during the eligibility phase which might have an impact on biomarker
      measures. This makes it important to capture dietary changes in the period
      between determination of eligibility and enrollment. Subjects (n=120) were
      randomized to follow a Healthy Eating or a Mediterranean Diet, each of which
      required substantial dietary record-keeping. The study completion rate was 78%,
      and subjects reported high satisfaction with study participation. Of the 93
      individuals who completed the study, only one refused the flexible sigmoidoscopy
      at the final visit. These findings suggest that flexible sigmoidoscopy does not
      appear to be a barrier for recruitment of high-risk individuals to an intensive
      dietary intervention trial, but that completing food records can be.

PMID- 22640926
TI  - DLK1(PREF1) is a negative regulator of adipogenesis in CD105+/CD90+/CD34+/CD31
      /FABP4- adipose-derived stromal cells from subcutaneous abdominal fat pats of
      adult women.
AB  - The main physiological function of adipose-derived stromal/progenitor cells (ASC)
      is to differentiate into adipocytes. ASC are most likely localized at
      perivascular sites in adipose tissues and retain the capacity to differentiate
      into multiple cell types. Although cell surface markers for ASC have been
      described, there is no complete consensus on the antigen expression pattern that
      will precisely define these cells. DLK1(PREF1) is an established marker for mouse
      adipocyte progenitors which inhibits adipogenesis. This suggests that DLK1(PREF1)
      could be a useful marker to characterize human ASC. The DLK1(PREF1) status of
      human ASC is however unknown. In the present study we isolated ASC from the
      heterogeneous stromal vascular fraction of subcutaneous abdominal fat pats of
      adult women. These cells were selected by their plastic adherence and expanded to
      passage 5. The ASC were characterized as relatively homogenous cell population
      with the capacity to differentiate in vitro into adipocytes, chondrocytes, and
      osteoblasts and the immunophenotype CD105+/CD90+/CD34+/CD31-/FABP4-. The ASC were
      positive for DLK1(PREF1) which was well expressed in proliferating and density
      arrested cells but downregulated in the course of adipogenic differentiation. To
      investigate whether DLK1(PREF1) plays a role in the regulation of adipogenesis in
      these cells RNAi-mediated knockdown experiments were conducted. Knockdown of
      DLK1(PREF1) in differentiating ASC resulted in a significant increase of the
      expression of the adipogenic key regulator PPARgamma2 and of the terminal
      adipogenic differentiation marker FABP4. We conclude that DLK1(PREF1) is well
      expressed in human ASC and acts as a negative regulator of adipogenesis.
      Moreover, DLK1(PREF1) could be a functional marker contributing to the
      characterization of human ASC.

PMID- 22640927
TI  - The effect of bone marrow-derived cells on diastolic function and exercise
      capacity in patients after acute myocardial infarction.
AB  - BACKGROUND: The early- to mid-term impact of bone-marrow-derived stem cells (BMC)
      on diastolic function and exercise capacity after acute myocardial infarction
      (AMI) remains controversial. We performed a systematic analysis to assess whether
      BMC transfer is related to an early improvement in diastolic function and
      exercise capacity after AMI. METHODS: Randomized controlled trials (RCTs) of BMC
      therapy after AMI were extracted from MEDLINE, EMBASE and CENTRAL and analyzed
      for a change in tissue Doppler annular early (Ea) and late diastolic (Aa)
      velocities, mitral inflow E velocity to tissue Doppler Ea (E/Ea) ratio, exercise
      time and exercise capacity. RESULTS: A total of 365 patients were included from 6
      trials. A greater improvement was observed in the E/Ea ratio after 1 year in the
      BMC group compared to the control group. Additionally, the BMC-treated patients
      had a larger improvement in exercise time, ventilation/CO2 production (VE/VCO2
      slope) and respiratory exchange ratio (RER) after 1 year. CONCLUSION: The results
      indicate that intracoronary BMC treatment in AMI patients leads to a mid-term
      improvement in diastolic function and exercise capacity.

PMID- 22640928
TI  - Benzophenones and xanthones from Garcinia cantleyana var. cantleyana and their
      inhibitory activities on human low-density lipoprotein oxidation and platelet
      aggregation.
AB  - Three benzophenones, 2,6,3',5'-tetrahydroxybenzophenone (1), 3,4,5,3',5'
      pentahydroxybenzophenone (3) and 3,5,3',5'-tetrahydroxy-4-methoxybenzophenone
      (4), as well as a xanthone, 1,3,6-trihydroxy-5-methoxy-7-(3'-methyl-2'-oxo-but-3'
      enyl)xanthone (9), were isolated from the twigs of Garcinia cantleyana var.
      cantleyana. Eight known compounds, 3,4,5,3'-tetrahydroxy benzophenone (2), 1,3,5
      trihydroxyxanthone (5), 1,3,8-trihydroxyxanthone (6), 2,4,7-trihydroxyxanthone
      (7), 1,3,5,7-tetrahydroxyxanthone (8), quercetin, glutin-5-en-3beta-ol and
      friedelin were also isolated. The structures of the compounds were elucidated by
      spectroscopic methods. The compounds were investigated for their ability to
      inhibit low-density lipoprotein (LDL) oxidation and platelet aggregation in human
      whole blood in vitro. Most of the compounds showed strong antioxidant activity
      with compound 8 showing the highest inhibition with an IC50 value of 0.5 MUM,
      comparable to that of probucol. Among the compounds tested, only compound 4
      exhibited strong inhibitory activity against platelet aggregation induced by
      arachidonic acid (AA), adenosine diphosphate (ADP) and collagen. Compounds 3, 5
      and 8 showed selective inhibitory activity on platelet aggregation induced by
      ADP.

PMID- 22640929
TI  - Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker
      fa/fa rats.
AB  - Obesity contributes to increased risk for several chronic diseases including
      cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid
      from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic
      syndrome in 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats
      received daily oral doses of xanthohumol at 0, 1.86, 5.64, and 16.9 mg/kg BW for
      6 weeks. All rats were maintained on a high fat (60% kcal) AIN-93G diet for 3
      weeks to induce severe obesity followed by a normal AIN-93G (15% kcal fat) diet
      for the last 3 weeks of the study. Weekly food intake and body weight were
      recorded. Plasma cholesterol, glucose, insulin, triglyceride, and monocyte
      chemoattractant protein-1 (MCP-1) levels were assessed using commercial assay
      kits. Plasma and liver tissue levels of XN and its metabolites were determined by
      liquid-chromatography tandem mass spectrometry. Plasma and liver tissue levels of
      xanthohumol were similar between low and medium dose groups and significantly
      (p<0.05) elevated in the highest dose group. There was a dose-dependent effect on
      body weight and plasma glucose levels. The highest dose group (n=6) had
      significantly lower plasma glucose levels compared to the control group (n=6) in
      male but not female rats. There was also a significant decrease in body weight
      for male rats in the highest dose group (16.9 mg/kg BW) compared to rats that
      received no xanthohumol, which was also not seen for female rats. Plasma
      cholesterol, insulin, triglycerides, and MCP-1 as well as food intake were not
      affected by treatment. The findings suggest that xanthohumol has beneficial
      effects on markers of metabolic syndrome.

PMID- 22640930
TI  - Omega-3 supplementation lowers inflammation in healthy middle-aged and older
      adults: a randomized controlled trial.
AB  - Observational studies have linked lower levels of omega-3 (n-3) polyunsaturated
      fatty acids (PUFAs) with inflammation and depression. This study was designed to
      determine whether n-3 supplementation would decrease serum cytokine production
      and depressive symptoms in 138 healthy middle-aged and older adults (average
      age=51.04, SD=7.76) who were sedentary and overweight (average BMI=30.59,
      SD=4.50). This three-arm randomized, placebo-controlled, double-blind 4-month
      trial compared responses to (1) 2.5 g/d n-3 PUFAs, or (2) 1.25 g/d n-3 PUFAs, or
      (3) placebo capsules that mirrored the proportions of fatty acids in the typical
      American diet. Serum interleukin-6 decreased by 10% and 12% in our low and high
      dose n-3 groups, respectively, compared to a 36% increase in the placebo group.
      Similarly, low and high dose n-3 groups showed modest 0.2% and -2.3% changes in
      serum tumor necrosis factor alpha, compared to a 12% increase in the control
      group. Depressive symptoms were quite low at baseline and did not change
      significantly in response to supplementation. Our data suggest that n-3 PUFAs can
      reduce inflammation in overweight, sedentary middle-aged and older adults, and
      thus could have broad health benefits. These data provide a window into the ways
      in which the n-3 PUFAs may impact disease initiation, progression, and
      resolution. ClinicalTrials.gov identifier: NCT00385723.

PMID- 22640931
TI  - Inferring biochemical reaction pathways: the case of the gemcitabine
      pharmacokinetics.
AB  - BACKGROUND: The representation of a biochemical system as a network is the
      precursor of any mathematical model of the processes driving the dynamics of that
      system. Pharmacokinetics uses mathematical models to describe the interactions
      between drug, and drug metabolites and targets and through the simulation of
      these models predicts drug levels and/or dynamic behaviors of drug entities in
      the body. Therefore, the development of computational techniques for inferring
      the interaction network of the drug entities and its kinetic parameters from
      observational data is raising great interest in the scientific community of
      pharmacologists. In fact, the network inference is a set of mathematical
      procedures deducing the structure of a model from the experimental data
      associated to the nodes of the network of interactions. In this paper, we deal
      with the inference of a pharmacokinetic network from the concentrations of the
      drug and its metabolites observed at discrete time points. RESULTS: The method of
      network inference presented in this paper is inspired by the theory of time
      lagged correlation inference with regard to the deduction of the interaction
      network, and on a maximum likelihood approach with regard to the estimation of
      the kinetic parameters of the network. Both network inference and parameter
      estimation have been designed specifically to identify systems of
      biotransformations, at the biochemical level, from noisy time-resolved
      experimental data. We use our inference method to deduce the metabolic pathway of
      the gemcitabine. The inputs to our inference algorithm are the experimental time
      series of the concentration of gemcitabine and its metabolites. The output is the
      set of reactions of the metabolic network of the gemcitabine. CONCLUSIONS: Time
      lagged correlation based inference pairs up to a probabilistic model of parameter
      inference from metabolites time series allows the identification of the
      microscopic pharmacokinetics and pharmacodynamics of a drug with a minimal a
      priori knowledge. In fact, the inference model presented in this paper is
      completely unsupervised. It takes as input the time series of the concetrations
      of the parent drug and its metabolites. The method, applied to the case study of
      the gemcitabine pharmacokinetics, shows good accuracy and sensitivity.

PMID- 22640933
TI  - Tight junctions, tight junction proteins and paracellular permeability across the
      gill epithelium of fishes: a review.
AB  - Paracellular permeability characteristics of the fish gill epithelium are broadly
      accepted to play a key role in piscine salt and water balance. This is typically
      associated with differences between gill epithelia of teleost fishes residing in
      seawater versus those in freshwater. In the former, the gill is 'leaky' to
      facilitate Na(+) secretion and in the latter, the gill is 'tight' to limit
      passive ion loss. However, studies in freshwater fishes also suggest that varying
      epithelial 'tightness' can impact ionoregulatory homeostasis. Paracellular
      permeability of vertebrate epithelia is largely controlled by the tight junction
      (TJ) complex, and the fish gill is no exception. In turn, the TJ complex is
      composed of TJ proteins, the abundance and properties of which determine the
      magnitude of paracellular solute movement. This review provides consolidated
      information on TJs in fish gills and summarizes recent progress in research that
      seeks to understand the molecular composition of fish gill TJ complexes and what
      environmental and systemic factors influence those components.

PMID- 22640934
TI  - Changes in the carpal tunnel while wearing the Manu(r) soft hand brace: a
      sonographic study.
AB  - We studied the effect of the Manu((r)) soft hand brace, which has been designed
      to relieve median nerve entrapment in carpal tunnel syndrome. An observational,
      controlled study was conducted in 10 participants, five with bilateral carpal
      tunnel syndrome and five controls, using sonography to study changes in the
      dimensions of the carpal tunnel before and while wearing the brace. An increase
      in transverse diameter, thinning of the flexor retinaculum, and displacement of
      the proximal insertion of the lumbrical muscle to the middle finger from the edge
      of the carpal tunnel were observed in patients while wearing the brace. The
      changes in the morphology of the carpal tunnel while wearing the Manu((r))
      support its use as an alternative to a night wrist splint.

PMID- 22640932
TI  - Chronic hyperoxia and the development of the carotid body.
AB  - Preterm infants often experience hyperoxia while receiving supplemental oxygen.
      Prolonged exposure to hyperoxia during development is associated with pathologies
      such as bronchopulmonary dysplasia and retinopathy of prematurity. Over the last
      25 years, however, experiments with animal models have revealed that moderate
      exposures to hyperoxia (e.g., 30-60% O(2) for days to weeks) can also have
      profound effects on the developing respiratory control system that may lead to
      hypoventilation and diminished responses to acute hypoxia. This plasticity, which
      is generally inducible only during critical periods of development, has a complex
      time course that includes both transient and permanent respiratory deficits.
      Although the molecular mechanisms of hyperoxia-induced plasticity are only
      beginning to be elucidated, it is clear that many of the respiratory effects are
      linked to abnormal morphological and functional development of the carotid body,
      the principal site of arterial O(2) chemoreception for respiratory control.
      Specifically, developmental hyperoxia reduces carotid body size, decreases the
      number of chemoafferent neurons, and (at least transiently) diminishes the O(2)
      sensitivity of individual carotid body glomus cells. Recent evidence suggests
      that hyperoxia may also directly or indirectly impact development of the central
      neural control of breathing. Collectively, these findings emphasize the
      vulnerability of the developing respiratory control system to environmental
      perturbations.

PMID- 22640935
TI  - A dorsally displaced capitate neck fracture combined with a transverse shear
      fracture of the triquetrum.

PMID- 22640936
TI  - Evaluation of biogenic amines content in chilean reserve varietal wines.
AB  - Biogenic amines play important roles in many physiological functions, but when
      they are ingested in high concentrations may produce severe adverse effects. The
      aim of this research was to evaluate the biogenic amine content in Chilean
      reserve varietal wines. A high performance liquid chromatography method was
      optimized and validated to quantify histamine, tyramine, spermine, spermidine,
      putrescine, cadaverine and phenylethylamine in Chilean wines. Derivatization and
      chromatographic conditions were optimized using a central composite design. Sixty
      reserve wines of the most important Chilean grape varieties were analyzed, i.e.
      Cabernet Sauvignon (n=11), Merlot (n=11), Carmenere (n=11), Syrah (n=10) and
      Sauvignon Blanc (n=10), as well as organic wines (n=7). Biogenic amines content
      ranged from 2.19 to 65.09 mg L(-1), no significant difference (P>0.05) was
      observed between Cabernet Sauvignon, Merlot and Carmenere but all showed
      statistically higher (P<0.05) concentrations than Sauvignon Blanc. Syrah wines
      showed no difference (P>0.05) with Cabernet Sauvignon, higher concentrations
      (P<0.05) than Sauvignon Blanc and lower than Merlot and Carmenere. Regarding
      biogenic amines profile, putrescine showed the highest concentration in all grape
      varieties.

PMID- 22640937
TI  - Suspected Nagashima-type palmoplantar keratosis with atypical hyperkeratotic
      lesions on the ears.

PMID- 22640938
TI  - Economic growth and decline in mortality in developing countries: an analysis of
      the World Bank development datasets.
AB  - OBJECTIVES: The 1999 World Bank report claimed that growth in gross domestic
      product (GDP) between 1960 and 1990 only accounted for 15% of concomitant growth
      in life expectancy in developing countries. These findings were used repeatedly
      by the World Health Organization (WHO) to support a policy shift away from
      promoting social and economic development, towards vertical technology-driven
      programmes. This paper updates the 1999 World Bank report using the World Bank's
      2005 dataset, providing a new assessment of the relative contribution of economic
      growth. STUDY DESIGN: Time-series analysis. METHODS: Cross-sectional time-series
      regression analysis using a random effect model of associations between GDP,
      education and technical progress and improved health outcomes. The proportion of
      improvement in health indicators between 1970 and 2000 associated with changes in
      GDP, education and technical progress was estimated. RESULTS: In 1970, a 1%
      difference in GDP between countries was associated with 6% difference in female
      (LEBF) and 5% male (LEBM) life expectancy at birth. By 2000, these values had
      increased to 14% and 12%, explaining most of the observed health gain. Excluding
      Europe and Central Asia, the proportion of the increase in LEBF and LEBM
      attributable to increased GDP was 31% and 33% in the present analysis, vs. 17%
      and 14%, respectively, estimated by the World Bank. In the poorest countries,
      higher GDPs were required in 2000 than in 1970 to achieve the same health
      outcomes. CONCLUSIONS: In the poorest countries, socio-economic change is likely
      to be a more important source of health improvement than technical progress.
      Technical progress, operating by increasing the size of the effect of a unit of
      GDP on health, is likely to benefit richer countries more than poorer countries,
      thereby increasing global health inequalities.

PMID- 22640939
TI  - Achievements in mental health outcome measurement in Australia: Reflections on
      progress made by the Australian Mental Health Outcomes and Classification Network
      (AMHOCN).
AB  - BACKGROUND: Australia's National Mental Health Strategy has emphasised the
      quality, effectiveness and efficiency of services, and has promoted the
      collection of outcomes and casemix data as a means of monitoring these. All
      public sector mental health services across Australia now routinely report
      outcomes and casemix data. Since late-2003, the Australian Mental Health Outcomes
      and Classification Network (AMHOCN) has received, processed, analysed and
      reported on outcome data at a national level, and played a training and service
      development role. This paper documents the history of AMHOCN's activities and
      achievements, with a view to providing lessons for others embarking on similar
      exercises. METHOD: We conducted a desktop review of relevant documents to
      summarise the history of AMHOCN. RESULTS: AMHOCN has operated within a framework
      that has provided an overarching structure to guide its activities but has been
      flexible enough to allow it to respond to changing priorities. With no precedents
      to draw upon, it has undertaken activities in an iterative fashion with an
      element of 'trial and error'. It has taken a multi-pronged approach to ensuring
      that data are of high quality: developing innovative technical solutions;
      fostering 'information literacy'; maximising the clinical utility of data at a
      local level; and producing reports that are meaningful to a range of audiences.
      CONCLUSION: AMHOCN's efforts have contributed to routine outcome measurement
      gaining a firm foothold in Australia's public sector mental health services.

PMID- 22640940
TI  - Towards a 3-dimensional atlas of the developing human embryo: the Amsterdam
      experience.
AB  - Knowledge of complex morphogenetic processes that occur during embryonic
      development is essential for understanding anatomy and to get insight in the
      pathogenesis of congenital malformations. Understanding these processes can be
      facilitated by using a three-dimensional (3D) developmental series of human
      embryos, which we aim to create in this project. Digital images of serial
      sections of 34 human embryos of the Carnegie Collection between Carnegie stages 7
      (15-17 days) and 23 (56-60 days) are used to create 3D reconstructions of
      different organ systems. The software package Amira is used to align the sections
      and to create the 3D reconstructions. In this midway evaluation we show the first
      results of the atlas, containing 34 embryos with more than 13.500 manually
      annotated sections. The 3D models can be interactively viewed within a 3D-pdf.
      This will be the first complete digital 3D human embryology atlas of this size,
      containing all developing organ systems.

PMID- 22640941
TI  - Dietary modulation of the biotransformation and genotoxicity of aflatoxin B(1).
AB  - Diet and its various components are consistently identified as among the most
      important 'risk factors' for cancer worldwide, yet great uncertainty remains
      regarding the relative contribution of nutritive (e.g., vitamins, calories) vs.
      non-nutritive (e.g., phytochemicals, fiber, contaminants) factors in both cancer
      induction and cancer prevention. Among the most potent known human dietary
      carcinogens is the mycotoxin, aflatoxin B(1) (AFB). AFB and related aflatoxins
      are produced as secondary metabolites by the molds Aspergillus flavus and
      Aspergillus parasiticus that commonly infect poorly stored foods including
      peanuts, pistachios, corn, and rice. AFB is a potent hepatocarcinogenic agent in
      numerous animal species, and has been implicated in the etiology of human
      hepatocellular carcinoma. Recent research has shown that many diet-derived
      factors have great potential to influence AFB biotransformation, and some
      efficiently protect from AFB-induced genotoxicity. One key mode of action for
      reducing AFB-induced carcinogenesis in experimental animals was shown to be the
      induction of detoxification enzymes such as certain glutathione-S-transferases
      that are regulated through the Keap1-Nrf2-ARE signaling pathway. Although initial
      studies utilized the dithiolthione drug, oltipraz, as a prototypical inducer of
      antioxidant response, dietary components such as suforaphane (SFN) are also
      effective inducers of this pathway in rodent models. However, human GSTs in
      general do not appear to be extensively induced by SFN, and GSTM1 - the only
      human GST with measurable catalytic activity toward aflatoxin B(1)-8,9-epoxide
      (AFBO; the genotoxic metabolite of AFB), does not appear to be induced by SFN, at
      least in human hepatocytes, even though its expression in human liver cells does
      appear to offer considerable protection against AFB-DNA damage. Although
      induction of detoxification pathways has served as the primary mechanistic focus
      of chemoprevention studies, protective effects of chemoprotective dietary
      components may also arise through a decrease in the rate of activation of AFB to
      AFBO. Dietary consumption of apiaceous vegetables inhibits CYP1A2 activity in
      humans, and it has been demonstrated that some compounds in those vegetables act
      as potent inhibitors of human CYP1A2 and cause reduced hCYP1A2-mediated
      mutagenicity of AFB. Other dietary compounds of different origin (e.g.,
      constituents of brassica vegetables and hops) have been shown to modify
      expression of human hepatic enzymes involved in the oxidation of AFB. SFN has
      been shown to protect animals from AFB-induced tumors, to reduce AFB biomarkers
      in humans in vivo and to reduce efficiently AFB adduct formation in human
      hepatocytes, although it appears that this protective effect is the result of
      repression of human hepatic CYP3A4 expression, rather than induction of
      protective GSTs, at least in human hepatocytes. If this mechanism were to occur
      in vivo in humans, it would raise safety concerns for the use of SFN as a
      chemoprotective agent as it may have important implications for drug-drug
      interactions in humans. A dietary chemoprevention pathway that is independent of
      AFB biotransformation is represented by the potential for dietary components,
      such as chlorophyllin, to tightly bind to and reduce the bioavailability of
      aflatoxins. Chlorophyllin has been shown to significantly reduce genotoxic AFB
      biomarkers in humans, and it therefore holds promise as a practical means of
      reducing the incidence of AFB-induced liver cancer. Recent reports have
      demonstrated that DNA repair mechanisms are inducible in mammalian systems and
      some diet-derived compounds elevated significantly the gene expression of enzymes
      potentially involved in nucleotide excision repair of AFB-DNA adducts. However,
      these are initial observations and more research is needed to determine if
      dietary modulation of DNA repair is a safe and effective approach to
      chemoprevention of AFB-induced liver cancer.

PMID- 22640942
TI  - Low efficacy of NcGRA7, NcSAG4, NcBSR4 and NcSRS9 formulated in poly-epsilon
      caprolactone against Neospora caninum infection in mice.
AB  - The protective efficacy of vaccination with Neospora caninum recombinant antigens
      was evaluated in Balb/c pregnant and non-pregnant mouse models of neosporosis. A
      major immunodominant dense granule protein (NcGRA7) and three bradyzoite-specific
      surface antigens (NcSAG4, NcBSR4 and NcSRS9) were expressed in Escherichia coli
      and encapsulated within poly-epsilon-caprolactone (PCL) nanoparticles for the
      first time. Good efficiencies of entrapment (greater than 50%) were obtained for
      all encapsulated proteins. Moreover, antigenicity was unaffected after
      formulation. Afterwards, separate groups of mice were immunised with the
      nanoparticles and were then challenged with N. caninum tachyzoites. High IgG1 and
      IgG2a antibody levels of anti-N. caninum and specific antibodies directed against
      recombinant proteins were developed by all of the immunised groups. Mice
      previously inoculated with encapsulated rNcGRA7 produced significant levels of
      IFN-gamma. However, in general, a low production of IFN-gamma was detected. This
      may indicate a failure in the complete liberation of antigens after immunisation
      or an incorrect balance of the Th1/Th2 response to combat acute neosporosis
      during pregnancy. In fact, high morbidity and mortality rates were observed in
      dams. Moreover, vertical transmission was not prevented, and high neonatal
      mortality rates occurred similarly among the groups. Despite the global absence
      of efficacy, the study reveals some results of positive efficacy regarding dams
      and pups' survival and parasite presence for NcSRS9 recombinant protein.
      Furthermore, vaccination with rNcGRA7 encapsulated alone or combined with rNcSAG4
      resulted in a slight decrease of parasite presence in non-pregnant mice. These
      promising results are further discussed to suggest new approaches that may be
      more suitable to test vaccine formulations based on bradyzoite stage-specific
      proteins.

PMID- 22640943
TI  - Human papilloma virus type 16-associated verruca vulgaris on the digits with
      multiple cancerous anogenital lesions.

PMID- 22640944
TI  - Nursing as the elusive core of care in hospitals.

PMID- 22640945
TI  - Implementing the new clinical nurse leader role while gleaning insights from the
      past.
AB  - This qualitative study explored the experiences of clinical nurse leaders (CNLs)
      as they implemented this new role. Twenty-four CNLs participated. Data were
      collected via an e-mail-distributed questionnaire. Data from open-ended questions
      were used to conduct a qualitative content analysis. Data were categorized
      according to question, key thoughts and phrases were established, and themes were
      determined. Findings revealed that nonsystematic role introduction was common.
      Two challenges to role implementation included role confusion and being
      overworked. The most positive aspect of the role was remaining close to the point
      of care. Participants noted that the overall response of the health care team to
      the role was positive despite participants' belief that the greatest roadblock to
      role success was the lack of support by nurse administrators. The support of
      nurse administrators and clear role expectations were viewed as essential for
      role sustain-ability. Understanding the experiences of CNLs as they launch this
      new role can provide insights for educators, administrators, CNLs, and other
      health care providers regarding the success and sustainability of the role. In
      addition, understanding the similarities between the clinical nurse specialist
      (CNS) role initiation in the past and the CNL role initiation today can foster
      the development of strategies for confronting the challenges of new role
      implementation.

PMID- 22640946
TI  - Course strategies for clinical nurse leader development.
AB  - The scope of the clinical nurse leader (CNL) is evolving in practice across the
      country. The preparation of this pivotal role in a complex healthcare environment
      has prompted the collaboration of nurse academics, nurse administrators, and
      clinicians to design unique educational experiences to maximize best practice.
      Knowledge attained regarding healthcare improvement and patient safety must not
      only be theoretical, but personal and application focused. Utilizing the American
      Association of Colleges of Nursing's CNL white paper and published resources
      faculty developed a clinical leadership course focused on active learning and
      reflection. Students explore concepts of improvement and quality related to
      business models of high functioning organizations including healthcare. Three key
      components of the course are described in detail; "quality is personal",
      executive interviews and the "5P" clinical microsystems assessment. Evaluation
      outcomes are discussed. Course content and innovative teaching/learning
      strategies for CNL are shared which may support the growth of CNL program
      development nationally.

PMID- 22640947
TI  - Trends in the nursing doctoral comprehensive examination process: a national
      survey.
AB  - The doctoral comprehensive or qualifying examination (CE/QE) is a traditional
      rite of passage into the community of scholars for the nursing profession. This
      exploratory, descriptive cross-sectional study examined trends in the process,
      timing, and methodology of comprehensive and qualifying examinations in nursing
      doctoral programs in the United States. Administrators from 45 schools responded
      to an online survey from 27 states across the country (37% response rate).
      Participants reported wide variations in the process. The most common method of
      implementation was the written take-home test (47%), two thirds of which had a
      subsequent oral examination. Eleven survey respondents (24%) reported using a
      form of the traditional written, timed, on-site examination; however, only 4 of
      these also followed up with an oral defense. Nine schools (20%) moved to a
      requirement for a written publishable paper; three schools consider the written
      proposal and its defense as the CE/QE. Approximately half had changed their
      policy in the past 5 years. With the increase in nursing doctor of philosophy
      programs over the past decade, information is needed to facilitate the
      development of methods to achieve program outcomes. An understanding of national
      CE/QE trends can provide a starting point for discussion and allow innovative
      ideas to meet the need of individual programs.

PMID- 22640948
TI  - Creating tomorrow's leaders and innovators through an RN-to-bachelor of science
      in nursing consortium curricular model.
AB  - The critical need to increase the number of baccalaureate-prepared RNs to improve
      the safety and quality of patient care in today's complex health care system is a
      pressing issue in health care. One part of the solution lies in the attainment of
      higher education of RNs prepared at the associate and diploma levels who make up
      the majority of the nursing workforce in the United States today. The Indiana
      University Schools of Nursing located throughout the state of Indiana
      collaborated to create a statewide RN-to-bachelor of science in nursing
      curriculum that is flexible, innovative, and meaningful. The plan focuses on the
      strengths and unique learning needs of returning RN students. Specifically, this
      curriculum offers year-round online courses in 7-week terms, which allows
      students to enter and exit the program within 1 year, and a curriculum with more
      choices and fewer constraints than is typical for baccalaureate nursing degrees.
      This learner-centered plan fully incorporates the American Association of
      Colleges of Nursing Essentials for Baccalaureate Education (2009) throughout the
      curriculum. It is conveniently delivered online, takes into account and gives
      credit for students' previous learning and work experience, and allows the
      students to pursue nursing specialty knowledge for college credit. Working
      together as a consortium to achieve these goals across an entire state with 8
      regional campuses required focused attention on the concerns and strengths of all
      the stakeholders and successful implementation of effective communication
      strategies.

PMID- 22640949
TI  - Newly graduated nurses' perception of competence and possible predictors: a cross
      sectional survey.
AB  - The aim of this study was to describe newly graduated nurses' own perception of
      competence and to identify possible predictors influencing their perceptions. The
      target population included nurses who graduated from nursing colleges in June
      2006. Data collection was carried out from October 2006 until April 2007 using
      the Nurse Competence Scale (NCS), the California Critical Thinking Disposition
      Inventory, and the Research Utilization Questionnaire. The response rate was 33%
      (n = 620). Pearson's chi-square test, Student t test, and regression analyses
      were used for statistical calculations. The respondents assessed their overall
      competence level as "good" and assessed themselves most competent in providing
      ethical and individualized nursing care. They assessed themselves least competent
      in evaluating outcomes and further development of patient care. Their use of
      competence explained between 40% (helping) and 10% (managing) of the variance
      within the NCS competence categories. Critical thinking (CT) was the most
      prominent predictor for perception of competence in all competence categories and
      the overall competence, alone explaining between 20% (NCS total score) and 9%
      (managing) of the variance. The finding that CT was a significant predictor for
      perception of competence may indicate that developing nursing students' CT
      abilities is valuable to increase newly graduated nurses' perception of
      competence.

PMID- 22640950
TI  - A teaching mentorship program to facilitate excellence in teaching and learning.
AB  - The impact of decreasing faculty numbers on the nursing shortage has been well
      documented. Mentoring is recognized as the most significant way to grow and
      nurture nurse educators. The purpose of this article was to describe the Teaching
      Mentorship Program within the College of Nursing Department of Biobehavioral
      Health Science at a Midwestern state university. The program activities are
      designed to facilitate new faculty members' transition from the role of nurse
      clinician to the role of nurse educator, to support the implementation of
      evidence-based teaching practices, and to encourage the development of teaching
      scholarship. Outcomes of the program include retention of new faculty, improved
      student satisfaction with the quality of instruction, and increased teaching
      scholarship activities. The program demonstrates the three hallmarks of an
      effective mentoring program. First, the program is supported by an institutional
      culture that values mentoring and provides it with an organizational home.
      Second, the Associate Department Head and primary mentor has been an educator for
      37 years with expertise in curriculum development, program evaluation, and
      teaching methodologies. Third, because the associate department head's principle
      role is to implement the program and serve as the primary mentor, her commitment
      is to provide flexible, timely access to faculty.

PMID- 22640951
TI  - Student drug testing in nursing education.
AB  - Nursing faculty and administrators have a responsibility to keep abreast of
      current research, legal regulations, and professional standards that affect
      students in the classroom and clinical setting. The purpose of this article is to
      examine whether empirical research supports the current trend of mandatory drug
      testing, provide a synopsis of current practice, and discuss the legal and
      ethical implications for nursing faculty.

PMID- 22640952
TI  - Reclaiming the essence of nursing: the meaning of an immersion experience in
      Honduras for RN to bachelor of science students.
AB  - Cultural immersion experiences incorporated in baccalaureate nursing programs
      have yielded positive short- and long-term effects on the personal and
      professional lives of the participants. Despite this evidence, little is known
      about how immersion experiences affect the RN student returning to school. The
      purpose of this phenomenological study was to uncover the meaning of a week-long
      immersion in Honduras for RN students (N = 8) and its impact on their
      professional practice upon return from Honduras. Data were analyzed through
      reflective journals and two focus groups conducted postimmersion experience.
      Transcripts were analyzed, and four themes emerged: from the outside looking in,
      struggling with dissonance, searching for meaning, and from the inside looking
      out. These themes combined to form the essence of the meaning of the experience:
      reclaiming the essence of nursing. Implications for practice, education, and
      research are addressed.

PMID- 22640953
TI  - Pathophysiology and medical treatment of pain in fibrous dysplasia of bone.
AB  - One of the most common complications of fibrous dysplasia of bone (FD) is bone
      pain. Usual pain killers are often of inadequate efficacy to control this bone
      pain. The mechanism of bone pain in FD remains uncertain, but by analogy with
      bone tumors one may consider that ectopic sprouting and formation of neuroma-like
      structures by sensory and sympathetic nerve fibers also occur in the dysplastic
      skeleton. Bone pain has been reported in up to 81% of adults and 49% of children.
      It affects predominantly the lower limbs and the spine. The degree of pain is
      highly variable and adults reports more pain than children. Bisphosphonates have
      been shown to reduce bone pain in uncontrolled studies. Their influence on bone
      strength remains unknown. In a randomized trial testing alendronate, bone pain
      was not significantly improved. Another trial assessing the effect of risedronate
      is ongoing. Possible future therapies include tocilizumab, denosumab and drugs
      targeting nerve growth factor and its receptor TrkA.

PMID- 22640954
TI  - Evolution and homologies of primate and modern human hand and forearm muscles,
      with notes on thumb movements and tool use.
AB  - In this paper, we explore how the results of a primate-wide higher-level
      phylogenetic analysis of muscle characters can improve our understanding of the
      evolution and homologies of the forearm and hand muscles of modern humans.
      Contrary to what is often suggested in the literature, none of the forearm and
      hand muscle structures usually present in modern humans are autapomorphic. All
      are found in one or more extant non-human primate taxa. What is unique is the
      particular combination of muscles. However, more muscles go to the thumb in
      modern humans than in almost all other primates, reinforcing the hypothesis that
      focal thumb movements probably played an important role in human evolution. What
      makes the modern human thumb myology special within the primate clade is not so
      much its intrinsic musculature but two extrinsic muscles, extensor pollicis
      brevis and flexor pollicis longus, that are otherwise only found in hylobatids.
      It is likely that these two forearm muscles play different functional roles in
      hylobatids and modern humans. In the former, the thumb is separated from
      elongated digits by a deep cleft and there is no pulp-to-pulp opposition, whereas
      modern humans exhibit powerful thumb flexion and greater manipulative abilities,
      such as those involved in the manufacture and use of tools. The functional and
      evolutionary significance of a third peculiar structure, the intrinsic hand
      structure that is often called the 'interosseous volaris primus of Henle' (and
      which we suggest is referred to as the musculus adductor pollicis accessorius) is
      still obscure. The presence of distinct contrahentes digitorum and
      intermetacarpales in adult chimpanzees is likely the result of prolonged or
      delayed development of the hand musculature of these apes. In relation to these
      structures, extant chimpanzees are more neotenic than modern humans.

PMID- 22640955
TI  - Palmitate promotes monocyte atherogenicity via de novo ceramide synthesis.
AB  - Elevated plasma free fatty acids (FAs) are associated with increased risk of
      cardiovascular disease. This study investigates the effects of the saturated FA
      palmitate and unsaturated FA oleate on monocyte phenotype and function.
      Incubation of human U937 and THP-1 monocytes with palmitate for 24h increased
      cell surface expression of integrin CD11b and scavenger receptor CD36 in a
      concentration-dependent manner with some decrease in mitochondrial reducing
      capacity at high concentration (300 MUM). Monocytes incubated with palmitate, but
      not oleate, showed increased uptake of oxidized LDL and increased adhesion to rat
      aortic endothelium, particularly at bifurcations. The palmitate-induced increase
      in CD11b and CD36 expression was associated with increased cellular C16 ceramide
      and sphingomyelin, loss of reduced glutathione, and increased reactive oxygen
      species (ROS). Increased monocyte surface CD11b and CD36 was inhibited by
      fumonisin B1, an inhibitor of de novo ceramide synthesis, but not by the
      superoxide dismutase mimetic MnTBap. In contrast, MnTBap prevented the
      mitochondrial ROS increase and metabolic inhibition due to 300MUM palmitate. This
      study demonstrates that in viable monocytes, palmitate but not oleate increases
      expression of surface CD11b and CD36. Palmitate increases monocyte adhesion to
      the aortic wall and promotes uptake of oxidized LDL and this involves de novo
      ceramide synthesis.

PMID- 22640956
TI  - A solution state diode using semiconductor polymer nanorods with nanogap
      electrodes.
AB  - A solution state polymer diode, which uses regioregular poly(3-hexylthiophene-2,5
      diyl) (P3HT):dichlorobenzene solution as the semiconductor between highly doped p
      type silicon and aluminum electrodes has been built. Electrodes separated by a 40
      nm gap enable intra-chain charge carrier transfer through the lengths of single
      polymer chains. This prevents chain to chain hopping and chain entanglements,
      increasing carrier mobility. The degradation with time and hysteresis effects of
      the diodes are measured. An optimal P3HT solution concentration of 6 mg ml(-1) is
      found. A current density of at least 300 mA cm(-2) is achieved, indicating at
      least a six-fold improvement in carrier mobility compared to previously
      fabricated solid state P3HT diodes.

PMID- 22640957
TI  - Lactoferrin and lactoferrin chimera inhibit damage caused by enteropathogenic
      Escherichia coli in HEp-2 cells.
AB  - Enteropathogenic Escherichia coli (EPEC) is an important cause of infant diarrhea
      in developing countries. It produces a characteristic intestinal
      histopathological lesion on enterocytes known as 'attaching and effacing' (A/E),
      and these two steps are mediated by a type-III secretory system. In the present
      study, we evaluated the effect on the initial host cell attachment step produced
      by bovine lactoferrin (bLF) and three synthetic peptides: lactoferricin (LFcin),
      lactoferrampin (LFampin) and LFchimera. A special focus was given to the
      hemolytic activity and EPEC-induced actin polymerization in HEp-2 cells, as well
      as to the espA gene expression, which produces the protein responsible for
      primary contact with the host cells. Results show that EPEC attachment to HEp-2
      cells was significantly suppressed by bLF and LFchimera at 125 and 40 MUM,
      respectively. EPEC-mediated actin polymerization was blocked by bLF and LFchimera
      at 88 and 99%, respectively. LFchimera inhibited the attachment and A/E lesion
      caused by EPEC in a dose-dependent manner. In the presence of 125 MUM bLF, the
      expression level of the espA gene was decreased by 50% compared to the untreated
      control. LFchimera at concentrations of 20 MUM and 40 MUM diminished the level of
      espA gene expression 100 and 1000 fold, respectively (P < 0.001). Although bLF,
      LFchimera, LFcin, and LFampin all significantly blocked the hemolysis produced by
      EPEC (P < 0.001), the two former compounds produced this effect at lower
      concentrations. These two compounds, bLF and LFchimera, were able to inhibit the
      first steps of the mechanism of the damage used by EPEC. This data suggests that
      LFchimera could provide protection against enteropathogens that share this
      mechanism.

PMID- 22640958
TI  - Computer-aided diagnosis of prostate cancer in the peripheral zone using
      multiparametric MRI.
AB  - This study evaluated a computer-assisted diagnosis (CADx) system for determining
      a likelihood measure of prostate cancer presence in the peripheral zone (PZ)
      based on multiparametric magnetic resonance (MR) imaging, including T2-weighted,
      diffusion-weighted and dynamic contrast-enhanced MRI at 1.5 T. Based on a feature
      set derived from grey-level images, including first-order statistics, Haralick
      features, gradient features, semi-quantitative and quantitative (pharmacokinetic
      modelling) dynamic parameters, four kinds of classifiers were trained and
      compared: nonlinear support vector machine (SVM), linear discriminant analysis, k
      nearest neighbours and naive Bayes classifiers. A set of feature selection
      methods based on t-test, mutual information and minimum-redundancy-maximum
      relevancy criteria were also compared. The aim was to discriminate between the
      relevant features as well as to create an efficient classifier using these
      features. The diagnostic performances of these different CADx schemes were
      evaluated based on a receiver operating characteristic (ROC) curve analysis. The
      evaluation database consisted of 30 sets of multiparametric MR images acquired
      from radical prostatectomy patients. Using histologic sections as the gold
      standard, both cancer and nonmalignant (but suspicious) tissues were annotated in
      consensus on all MR images by two radiologists, a histopathologist and a
      researcher. Benign tissue regions of interest (ROIs) were also delineated in the
      remaining prostate PZ. This resulted in a series of 42 cancer ROIs, 49 benign but
      suspicious ROIs and 124 nonsuspicious benign ROIs. From the outputs of all
      evaluated feature selection methods on the test bench, a restrictive set of about
      15 highly informative features coming from all MR sequences was discriminated,
      thus confirming the validity of the multiparametric approach. Quantitative
      evaluation of the diagnostic performance yielded a maximal area under the ROC
      curve (AUC) of 0.89 (0.81-0.94) for the discrimination of the malignant versus
      nonmalignant tissues and 0.82 (0.73-0.90) for the discrimination of the malignant
      versus suspicious tissues when combining the t-test feature selection approach
      with a SVM classifier. A preliminary comparison showed that the optimal CADx
      scheme mimicked, in terms of AUC, the human experts in differentiating malignant
      from suspicious tissues, thus demonstrating its potential for assisting cancer
      identification in the PZ.

PMID- 22640959
TI  - Age-dependent acoustic and microelastic properties of red blood cells determined
      by vector contrast acoustic microscopy.
AB  - Variations of the mechanical properties of red blood cells that occur during
      their life span have long been an intriguing task for investigations. The
      research presented is based on noninvasive monitoring of red blood cells of
      different ages performed by scanning acoustic microscopy with magnitude and phase
      contrast. The characteristic signature of fixed cells from groups of three
      different ages fractionated according to mass density is obtained from the
      acoustic microscope images, with the data represented in polar graphs. The
      analysis of these data enables the determination of averaged values for the
      velocities of ultrasound propagating in the cells from the different groups
      ranging from (1,681 +/- 16) m s(-1) in the youngest to (1,986 +/- 20) m s(-1) in
      the oldest group. The determined bulk modulus varies with age from (3.04 +/-
      0.05) GPa to (4.34 +/- 0.08) GPa. An approach to determine for an age-mixed
      population of red blood cells, collected from a healthy person, the age of the
      individual cells and the age dependence of the cell parameters including density,
      velocity, and attenuation of longitudinal polarized ultrasonic waves traveling in
      the cells is demonstrated.

PMID- 22640960
TI  - delta- and gamma-tocotrienols induce classical ultrastructural apoptotic changes
      in human T lymphoblastic leukemic cells.
AB  - Tocotrienols are isomers of the vitamin E family, which have been reported to
      exert cytotoxic effects in various cancer cells. Although there have been some
      reports on the effects of tocotrienols in leukemic cells, ultrastructural
      evidence of tocotrienol-induced apoptotic cell death in leukemic cells is
      lacking. The present study investigated the effects of three isomers of
      tocotrienols (alpha, delta, and gamma) on a human T lymphoblastic leukemic cell
      line (CEM-SS). Cell viability assays showed that all three isomers had cytotoxic
      effects (p < 0.05) on CEM-SS cells with delta-tocotrienol being the most potent.
      Transmission electron microscopy showed that the cytotoxic effects by delta- and
      gamma-tocotrienols were through the induction of an apoptotic pathway as
      demonstrated by the classical ultrastructural apoptotic changes characterized by
      peripheral nuclear chromatin condensation and nuclear fragmentation. These
      findings were confirmed biochemically by the demonstration of phosphatidylserine
      externalization via flow cytometry analysis. This is the first study showing
      classical ultrastructural apoptotic changes induced by delta- and gamma
      tocotrienols in human T lymphoblastic leukemic cells.

PMID- 22640961
TI  - Heat-induced antigen retrieval applied in zebrafish: whole-mount in situ
      immunofluorescence microscopy.
AB  - Whole-mount immunofluorescence technique provides a way to reveal integrated
      expression patterns of biological molecules in individuals. Well-documented
      morphological preservation ability in biology makes aldehydes the fixative of
      choice. Cross-linking among biocomponents and aldehydes is the key for
      maintaining morphology but masks the biological molecules for immunodetection.
      This study performs an easily accessible method by applying heat-induced
      retrieval, which can rescue the antigenicity of the proteins and also enhance the
      labeling sensitivity of the fluorescence dye in overfixed zebrafish embryos. The
      results show that the immunoreactivities of antibodies to myosin in the muscles,
      green fluorescent protein in the blood vessels and the nuclei in the cells can be
      recovered significantly, and the morphology of the zebrafish embryos, even the
      fragile mutants, is at the same time well maintained. Therefore, we provide a
      choice for antigen retrieval, which is effective for whole-mount
      immunofluorescence microscopy.

PMID- 22640962
TI  - Differential resin-dentin bonds created after caries removal with polymer burs.
AB  - The objective of this article was to investigate the effect of carbide and
      polymer burs caries removal methods on the bond strength of different adhesives
      to dentin. Resin restorations were performed in sound and caries-affected dentin,
      after using polymer or carbide burs and bonding with four different adhesive
      (Single bond, SB; Clearfil SE bond, SEB; FL-Bond II, FLB; and Fuji II-LC, FUJI).
      Microtensile bond strength (MTBS) was measured. Data were analyzed with ANOVA and
      Student-Newman-Keuls tests. Debonded surfaces were observed by scanning electron
      microscopy. Bonded interfaces were examined using light microscopy (Masson's
      trichrome staining). In sound dentin, MTBS was similar for SEB and SB, and higher
      than that of FLB and FUJI. Bond strength to carbide bur prepared dentin was
      similar for SB, SEB, and FLB; FUJI presented the lowest. SB applied on polymer
      bur excavated dentin presented similar values to those of the carbide bur group;
      MTBS attained by SEB, FLB, and FUJI decreased when bonding to dentin treated with
      polymer burs; FUJI yielded pretesting failures in all specimens. Polymer burs
      created a thick smear layer that was not infiltrated by tested self-etching
      agents. The bonding effectiveness of self-etching and glass-ionomer-like
      adhesives to dentin decreased when polymer burs were used.

PMID- 22640963
TI  - Data-constrained microstructure characterization with multispectrum X-ray micro
      CT.
AB  - Conventional X-ray microcomputed tomography (micro-CT) is not usually sufficient
      to determine microscopic compositional distributions as it is limited to
      measuring the X-ray attenuation of the sample, which for a given dataset can be
      similar for materials of different composition. In contrast, the present work
      enables three-dimensional compositional analysis with a data-constrained
      microstructure (DCM) modeling methodology, which uses two or more CT datasets
      acquired with different X-ray spectra and incorporates them as model constraints.
      For providing input data for DCM, we have also developed a method of micro-CT
      data collection that enables two datasets with different X-ray spectra to be
      acquired in parallel. Such data are used together with the DCM methodology to
      predict the distributions of corrosion inhibitor and filler in a polymer matrix.
      The DCM-predicted compositional microstructures have a reasonable agreement with
      energy dispersive X-ray images taken on the sample surface.

PMID- 22640964
TI  - In situ analytical electron microscopy studies of redox reactions at a YSZ/Pt
      interface.
AB  - Redox reactions were studied at a single yttria-stabilized zirconia (YSZ)/Pt
      electrode interface, in parallel with pure YSZ with no catalyst electrode, by in
      situ analytical electron microscopy at elevated temperatures and in an oxygen
      atmosphere. In situ electron holography showed that the oxide underwent reduction
      at elevated temperatures in a vacuum and was consequently reoxidized upon
      exposure to an oxygen flux at the same temperature. In situ energy loss
      spectroscopy measurements were in agreement with in situ electron holography
      observations and indicated that the oxidation state of the host cation zirconium
      was altered in the reduced state of the YSZ to the metastable state Zr(3+).

PMID- 22640965
TI  - KrF pulsed laser ablation of thin films made from fluorinated heterocyclic
      poly(naphthyl-imide)s.
AB  - Among the many aspects of laser ablation, development of conical structures
      induced by excimer laser radiation on polyimide surfaces has been thoroughly
      investigated. Because the mechanisms that produce these surface textures are not
      fully understood, two theories, photochemical bond breaking and thermal reaction,
      have been introduced. Here we present the first study of ultraviolet laser
      ablation behavior of thin films made from fluorinated poly(naphthyl-imide)s
      containing oxadiazole rings and the investigation of the mechanism of cone-like
      structure formation at two laser fluences, 57 and 240 mJ/cm(2). The morphology of
      thin films before and after laser ablation was studied by using various
      spectroscopy techniques such as Fourier transform infrared spectroscopy, time
      resolved emission and X-ray photoelectron spectroscopy, atomic force microscopy,
      and contact angle measurements. All of the data suggest impurities shielded at
      low fluence radiation (57 mJ/cm(2)) and a radiation hardening process at high
      value fluence (240 mJ/cm(2)), which are proposed as the main mechanisms for laser
      ablation of our polyimide films, and we bring evidence to support them.

PMID- 22640966
TI  - Identifying hexagonal boron nitride monolayers by transmission electron
      microscopy.
AB  - Multislice simulations in the transmission electron microscope (TEM) were used to
      examine changes in annular-dark-field scanning TEM (ADF-STEM) images,
      conventional bright-field TEM (BF-CTEM) images, and selected-area electron
      diffraction (SAED) patterns as atomically thin hexagonal boron nitride (h-BN)
      samples are tilted up to 500 mrad off of the [0001] zone axis. For monolayer h-BN
      the contrast of ADF-STEM images and SAED patterns does not change with tilt in
      this range, while the contrast of BF-CTEM images does change; h-BN multilayer
      contrast varies strongly with tilt for ADF-STEM imaging, BF-CTEM imaging, and
      SAED. These results indicate that tilt series analysis in ADF-STEM image mode or
      SAED mode should permit identification of h-BN monolayers from raw TEM data as
      well as from quantitative post-processing.

PMID- 22640967
TI  - Nanoprobe fourier-transform photoabsorption spectroscopy using a supercontinuum
      light source.
AB  - A scheme of photoabsorption spectroscopy based on scanning tunneling microscopy
      (STM) has been developed by using a supercontinuum light as the wideband light
      source of a Fourier transform interferometer for spectroscopic measurements. The
      performance was demonstrated for a sample of GaAs. The proof-of-concept test
      showed that the use of the supercontinuum light instead of halogen lamps greatly
      enhances the signal-to-noise ratio due to the high brilliance of the
      supercontinuum light emitted from a small core of the photonic crystal fiber that
      enables tight focusing of the spectroscopy light onto the sample beneath the STM
      tip.

PMID- 22640968
TI  - Atomic-scale imaging and spectroscopy for in situ liquid scanning transmission
      electron microscopy.
AB  - Observation of growth, synthesis, dynamics, and electrochemical reactions in the
      liquid state is an important yet largely unstudied aspect of nanotechnology. The
      only techniques that can potentially provide the insights necessary to advance
      our understanding of these mechanisms is simultaneous atomic-scale imaging and
      quantitative chemical analysis (through spectroscopy) under environmental
      conditions in the transmission electron microscope. In this study we describe the
      experimental and technical conditions necessary to obtain electron energy loss
      (EEL) spectra from a nanoparticle in colloidal suspension using aberration
      corrected scanning transmission electron microscopy (STEM) combined with the
      environmental liquid stage. At a fluid path length below 400 nm, atomic
      resolution images can be obtained and simultaneous compositional analysis can be
      achieved. We show that EEL spectroscopy can be used to quantify the total fluid
      path length around the nanoparticle and demonstrate that characteristic core-loss
      signals from the suspended nanoparticles can be resolved and analyzed to provide
      information on the local interfacial chemistry with the surrounding environment.
      The combined approach using aberration-corrected STEM and EEL spectra with the in
      situ fluid stage demonstrates a plenary platform for detailed investigations of
      solution-based catalysis.

PMID- 22640969
TI  - Misdiagnosis and patient negation: a case of universal vitiligo.

PMID- 22640970
TI  - The clinicopathologic association of c-MET overexpression in Iranian gastric
      carcinomas; an immunohistochemical study of tissue microarrays.
AB  - BACKGROUND: c-MET is an oncogene protein that plays important role in gastric
      carcinogenesis and has been introduced as a prognostic marker and potential
      therapeutic target. The aim of this study was to evaluate the frequency of c-MET
      overexpression and its relationship with clinicopathological variables in gastric
      cancer of Iranian population using tissue microarray. METHODS: In a cross
      sectional study, representative paraffin blocks of 130 patients with gastric
      carcinoma treated by curative gastrectomy during a 2 years period of 2008-2009 in
      two university hospitals in Tehran-Iran were collected in tissue microarray and c
      MET expression was studied by immunohistochemical staining. RESULTS: Finally 124
      cases were evaluated, constituted of 99 male and 25 female with the average age
      of 61.5 years. In 71% (88/124) of tumors, c-MET high expression was found. c-MET
      high expression was more associated with intestinal than diffuse tumor type (P =
      0.04), deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014), neural
      invasion (P = 0.002) and advanced TNM staging, stage 3 and 4 versus stage 1 and2
      (P = 0.044). The c-MET high expression was not associated with age, sex, tumor
      location, differentiation grade and distant metastasis, but relative associations
      with lymph node metastasis (P = 0.065) and vascular invasion (P = 0.078) were
      observed. CONCLUSIONS: c-MET oncogene protein was frequently overexpressed in
      Iranian gastric carcinomas and it was related to clinicopathological
      characteristics such as tumor type, depth of invasion, neural invasion and TNM
      staging. It can also support the idea that c-MET is a potential marker for target
      therapy in Iranian gastric cancer. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429.

PMID- 22640972
TI  - Treatment strategies for acute coronary syndrome with severe mitral regurgitation
      and their effects on short- and long-term prognosis.
AB  - Mitral regurgitation (MR) of even mild severity affects the prognosis of patients
      with acute coronary syndrome (ACS). The present study retrospectively analyzed
      1,142 patients with ACS and MR of varying severity. Of the 95 patients with
      severe MR, 57 (60%) underwent primary percutaneous coronary intervention only and
      38 (40%) underwent coronary artery bypass grafting (CABG) and mitral valve
      replacement (MVR). The severity of MR was significantly associated with the risk
      of heart failure but not with in-hospital or long-term mortality. In patients
      with severe MR, in-hospital mortality was no greater in those treated with CABG
      and MVR than in those treated with percutaneous coronary intervention alone.
      However, the incidence of long-term hard events (heart failure and all-cause
      mortality) was lower in those who had received the combined treatment.
      Multivariate analysis showed that, compared to percutaneous coronary intervention
      alone, CABG combined with MVR at the acute phase of ACS resulted in a
      significantly improved prognosis (odds ratio 0.172, 95% confidence interval 0.046
      to 0.649, p = 0.009), even after adjusting for age, left ventricular filling
      pressure, and ejection fraction. In conclusion, the severity of MR in patients
      with ACS is associated with long-term heart failure events. Even at the acute
      phase of ACS, CABG combined with MVR results in an acceptable in-hospital
      mortality rate. The combined strategy also reduced the long-term hard events.

PMID- 22640973
TI  - Optical coherence tomography and highly sensitivity troponin T for evaluating
      cardiac allograft vasculopathy.
AB  - Cardiac allograft vasculopathy (CAV) is a major impediment to long-term graft
      survival after heart transplantation. Intravascular ultrasound (IVUS) is more
      sensitive than coronary angiography for diagnosis, but the identification of
      specific plaque components or plaque composition is limited. In addition, there
      is an evident need for other noninvasive tools for diagnosing CAV. The aim of
      this study was to assess the utility of 2 new techniques for evaluating CAV:
      optical coherence tomography (OCT), and new high-sensitivity troponin T (hsTnT)
      assays. In 21 heart transplantation patients, coronary arteriography with IVUS
      and OCT were performed. Maximal intimal thickness (MIT) and luminal area at the
      most severe site were measured using the 2 techniques. Immediately before cardiac
      catheterization, blood samples were obtained and hsTnT levels measured. The
      evaluation of CAV by OCT showed a good correlation with IVUS measurements, with a
      mean difference in MIT of 0.0033 (95% confidence interval -0.049 to 0.043),
      taking advantage of lower interobserver variability (r = 0.94 for OCT vs r = 0.78
      for IVUS) and better plaque characterization. When independent predictors of MIT
      were assessed in a multiple linear regression model, time after transplantation
      (beta = 0.488, p = 0.004) and hsTnT (beta = 0.392, p = 0.011) were the only
      independent predictors of MIT (R(2) = 0.591). In conclusion, this study is the
      first to evaluate 2 new techniques, OCT and hsTnT, in the challenging setting of
      CAV. The findings suggest that OCT provides lower interobserver variability and
      better plaque characterization than IVUS. Also, hsTnT could become a useful tool
      for ruling out CAV.

PMID- 22640971
TI  - McCune-Albright syndrome and the extraskeletal manifestations of fibrous
      dysplasia.
AB  - Fibrous dysplasia (FD) is sometimes accompanied by extraskeletal manifestations
      that can include any combination of cafe-au-lait macules, hyperfunctioning
      endocrinopathies, such as gonadotropin-independent precocious puberty,
      hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting,
      and/or Cushing syndrome, as well as other less common features. The combination
      of any of these findings, with or without FD, is known as McCune-Albright
      syndrome (MAS). The broad spectrum of involved tissues and the unpredictable
      combination of findings owe to the fact that molecular defect is due to dominant
      activating mutations in the widely expressed signaling protein, Gsalpha, and the
      fact these mutations arises sporadically, often times early in development, prior
      to gastrulation, and can distribute across many or few tissues.The complexity can
      be mastered by a systematic screening of potentially involved tissues and
      cognizance that the pattern of involved tissues is established, to some degree,
      in utero. Thorough testing allows the clinician to establish, often times at
      presentation, the full extent of the disease, and importantly as well what
      tissues are unaffected. Treatment and follow-up can then be focused on affected
      systems and a meaningful prognosis can be offered to the patient and family. The
      authors outline screening and treatment strategies that allow for effective
      management of the extraskeletal manifestations of FD.

PMID- 22640974
TI  - Protein fragments from the VEGF binding domain of fibronectin are expressed in
      distinct spatial and temporal patterns during venous thrombus resolution.

PMID- 22640975
TI  - Generalised equations for the prediction of percentage body fat by anthropometry
      in adult men and women aged 18-81 years.
AB  - Anthropometric data indicate that the human phenotype is changing. Today's adult
      is greater in stature, body mass and fat mass. Accurate measurement of body
      composition is necessary to maintain surveillance of obesity within the
      population and to evaluate associated interventions. The aim of the present study
      was to construct and validate generalised equations for percentage body fat (%BF)
      prediction from anthropometry in 1136 adult men and women. Reference values for
      %BF were obtained using dual-energy X-ray absorptiometry. Skinfold thickness (SF)
      at ten sites and girth (G) at seven sites were measured on 736 men and women aged
      18-81 years (%BF 5.1-56.8%). Quantile regression was employed to construct
      prediction equations from age and log-transformed SF and G measures. These
      equations were then cross-validated on a cohort of 400 subjects of similar age
      and fatness. The following generalised equations were found to most accurately
      predict %BF: Men: (age x 0.1) + (logtricepsSF x 7.6) + (logmidaxillaSF x 8.8) +
      (logsuprspinaleSF x 11.9) - 11.3 (standard error of the estimate: 2.5%, 95%
      limits of agreement: - 4.8, + 4.9) Women: (age x 0.1) + (logabdominalG x 39.4) +
      (logmidaxillaSF x 4.9) + (logbicepsSF x 11.0) + (logmedialcalfSF x 9.1) - 73.5
      (standard error of the estimate: 3.0%, 95% limits of agreement: - 5.7, + 5.9)
      These generalised anthropometric equations accurately predict %BF and are
      suitable for the measurement of %BF in adult men and women of varying levels of
      fatness across the lifespan.

PMID- 22640976
TI  - Repeated exposures to chlorpyrifos lead to spatial memory retrieval impairment
      and motor activity alteration.
AB  - Chlorpyrifos (CPF) is one of the most commonly used insecticides throughout the
      world and has become one of the major pesticides detected in farm products.
      Chronic exposures to CPF, especially at the dosages without eliciting any
      systemic toxicity, require greater attention. The purpose of this study was,
      therefore, to evaluate the behavioral effects of repeated low doses (doses that
      do not produce overt signs of cholinergic toxicity) of CPF in adult rats. Male
      rats were given 0, 1.0, 5.0 or 10.0mg/kg of CPF through intragastric
      administration daily for 4 consecutive weeks. The behavioral functions were
      assessed in a series of behavioral tests, including water maze task, open-field
      test, grip strength and rotarod test. Furthermore, the present study was designed
      to evaluate the effects of repeated exposures to CPF on water maze recall and not
      acquisition. The results showed that the selected doses only had mild inhibition
      effects on cholinesterase activity, and have no effects on weight gain and daily
      food consumption. Performances in the spatial retention task (Morris water maze)
      were impaired after the 4-week exposure to CPF, but the performances of grip
      strength and rotarod test were not affected. Motor activities in the open field
      were changed, especially the time spent in the central zone increased. The
      results indicated that repeated exposures to low doses of CPF may lead to spatial
      recall impairments, behavioral abnormalities. However, the underlying mechanism
      needs further investigations.

PMID- 22640977
TI  - Ubiquinone in cardiac arrest: from bathroom to bedside.

PMID- 22640978
TI  - Multiple MDMA (Ecstasy) overdoses at a rave event: a case series.
AB  - Twelve patients with 3,4-methylenedioxymethamphetamine (MDMA) toxicity from a
      single rave event presented to multiple San Francisco Bay area hospitals with
      various life-threatening complications including seizures and hyperthermia. Eight
      required emergent endotracheal intubation and six had hypotension. Hyperkalemia,
      acute kidney injury, and rhabdomyolysis were present in most of the patients. In
      all, 2 patients died, 4 survived with permanent neurologic, musculoskeletal,
      and/or renal sequelae, and 6 survived without any apparent lasting deficits.
      Hyperthermia was present in 10 patients and was severe (40.9-43 degrees  C) in 7.
      Using multiple cooling methods, the average time to achieve cooling was 2.7
      hours. Serum drug analysis was performed on 3 patients, demonstrating toxic MDMA
      concentrations without the presence of other xenobiotics. Two capsules
      confiscated by police at the event contained 82% and 98% MDMA, respectively,
      without other pharmacologically active compounds. Capsule #2 contained 270 mg
      MDMA, which is more than twice the amount of MDMA usually contained in 1 dose.
      The MDMA-induced hyperthermia significantly contributed to the morbidity and
      mortality in this case series. Factors contributing to the severity of the
      hyperthermia include ingestion of large doses of MDMA, a warm ambient
      environment, and physical exertion. 

PMID- 22640979
TI  - N-acetylcysteine for the prevention of stricture after circumferential endoscopic
      submucosal dissection of the esophagus: a randomized trial in a porcine model.
AB  - BACKGROUND: Circumferential endoscopic submucosal dissection (CESD) of the
      esophagus would allow for both the eradication of Barrett's esophagus and its
      related complications, such as advanced neoplasia. However, such procedures
      generally induce inflammatory repair resulting in a fibrotic stricture. N
      acetylcysteine (NAC) is an antioxidant that has shown some efficacy against
      pulmonary and hepatic fibrosis. The aim of our study was to evaluate the benefit
      of NAC in the prevention of esophageal cicatricial stricture after CESD in a
      swine model. ANIMALS AND METHODS: Two groups of six pigs each were subjected to
      general anesthesia and CESD: after randomization, a first group received an oral
      NAC treatment regimen of 100 mg/kg/day, initiated one week before the procedure,
      whereas a second group was followed without any prophylactic treatment. Follow-up
      endoscopies took place seven, fourteen, twenty-one, and twenty-eight days after
      CESD. Necropsy, histological assessment of esophageal inflammation, and fibrosis
      were performed on day 28. RESULTS: The median esophageal lumen diameter on day 21
      (main judgment criterion) was 4 mm (range 2 to 5) in group 1 and 3 mm (range 1 to
      7) in group 2 (P = 0.95). No significant difference was observed between the two
      groups regarding clinical evaluation (time before onset of clinically significant
      esophageal obstruction), number of dilations, esophageal inflammation and
      fibrosis, or oxidative stress damage on immunohistochemistry. CONCLUSIONS:
      Despite its antioxidant effect, systemic administration of NAC did not show
      significant benefit on esophageal fibrosis in our animal model of esophageal
      wound healing within the experimental conditions of this study. Since the
      administered doses were relatively high, it seems unlikely that NAC might be a
      valuable option for the prevention of post-endoscopic esophageal stricture.

PMID- 22640980
TI  - Controlled dielectrophoretic nanowire self-assembly using atomic layer deposition
      and suspended microfabricated electrodes.
AB  - Effects of design and materials on the dielectrophoretic self-assembly of
      individual gallium nitride nanowires (GaN NWs) onto microfabricated electrodes
      have been experimentally investigated. The use of TiO(2) surface coating
      generated by atomic layer deposition (ALD) improves dielectrophoretic assembly
      yield of individual GaN nanowires on microfabricated structures by as much as
      67%. With a titanium dioxide coating, individual nanowires were placed across
      suspended electrode pairs in 46% of tests (147 out of 320 total), versus 28% of
      tests (88 out of 320 total tests) that used uncoated GaN NWs. An additional
      result from these tests was that suspending the electrodes 2.75 MUm above the
      substrate corresponded with up to 15.8% improvement in overall assembly yield
      over that of electrodes fabricated directly on the substrate.

PMID- 22640981
TI  - Theoretical study and pathways for nanoparticle capture during solidification of
      metal melt.
AB  - Nanocomposites can provide exciting physical, chemical, and mechanical properties
      for numerous applications. The solidification processing method has great
      potential for economical fabrication of bulk nanocomposites, especially for those
      with crystalline materials as the matrix, such as metal matrix nanocomposites
      (MMNCs). However, it is extremely difficult to effectively capture nanoparticles
      (less than 100 nm) into the solidification fronts during solidification. It is
      thus very important to initiate a theoretical study to examine the physics that
      governs the interactions between nanoparticles and the solidification front, and
      to provide enabling pathways for effective nanoparticle capture during
      solidification. The aim of this paper is to establish a theoretical framework for
      the fundamental understanding of nanoparticle capture during solidification of
      metal melt in order to obtain bulk MMNCs. A thermodynamically favorable condition
      is set as the starting point for further theoretical analysis of the three-party
      model system, namely a nanoparticle-metal-melt-solidification front. Three key
      interaction potentials, the interfacial energy at short range (0.2-0.4 nm), the
      van der Waals potential (especially at a longer range beyond 0.4 nm and up to ~10
      nm) and the Brownian potential, were studied. Three possible pathways for
      nanoparticle capture were thus devised: viscous capture, Brownian capture and
      spontaneous capture. Spontaneous capture is proposed as the most favorable for
      nanoparticle capture during solidification of metal melt. The theoretical model
      of nanoparticle capture from this study will serve as a powerful tool for future
      experimental studies to realize exciting functionalities offered by bulk MMNCs.

PMID- 22640982
TI  - Unilateral telangiectasia macularis eruptiva perstans with a clear demarcation at
      the midline of the trunk.

PMID- 22640983
TI  - A risk score for predicting the incidence of type 2 diabetes in a middle-aged
      Korean cohort: the Korean genome and epidemiology study.
AB  - BACKGROUND: The aim of this study was to develop a risk score to predict the 4
      year risk of diabetes in a middle-aged Korean cohort. METHODS AND RESULTS:
      Participants without diabetes (6,342 participants, aged 40-69 years) were
      included and biennial follow ups were conducted. A logistic regression analysis
      was used to construct the models. The basic model was based on simple information
      such as age, parental or sibling history of diabetes, smoking status, body mass
      index, and hypertension, while clinical model 1 was constructed by adding
      biochemical tests such as fasting plasma glucose, high-density lipoprotein
      cholesterol and triglycerides to the basic model; clinical model 2 further added
      glycated hemoglobin (HbA(1c)) to clinical model 1. The model accuracy was
      assessed using area under a receiver operating characteristic (AROC) curve and
      the Hosmer-Lemeshow statistics. Both net reclassification improvement (NRI) and
      integrated discrimination improvement (IDI) were calculated to determine the
      contribution of HbA(1c). Two clinical models improved model discrimination
      (AROC=0.75 and 0.77) when compared with the basic model (AROC=0.65). The addition
      of HbA(1c) to clinical model 1 increased AROC by only 0.02 despite its high
      impact on the prediction of diabetes (odds ratio=2.66). However, the NRI and IDI
      were significantly improved with the addition of HbA(1c) Therefore, a risk score
      system was developed to estimate the 4-year risk of diabetes based on clinical
      model 2. CONCLUSIONS: A risk score derived from simple biochemical examinations
      including HbA(1c) can help identify those at a high risk of diabetes in a middle
      aged Korean cohort.

PMID- 22640984
TI  - Impaired coronary flow reserve as a marker of microvascular dysfunction to
      predict long-term cardiovascular outcomes, acute coronary syndrome and the
      development of heart failure.
AB  - BACKGROUND: In the absence of obstructive coronary narrowing, impaired coronary
      flow reserve (CFR) represents coronary microvascular dysfunction. Transthoracic
      Doppler echocardiography (TTDE) allows non-invasive measurement of CFR in the
      left anterior descending (LAD) artery. This study aimed to assess the prognostic
      value of TTDE-derived CFR (as a marker of microvascular function) in predicting
      long-term cardiovascular events, acute coronary syndrome (ACS) events, and the
      development of heart failure (HF). METHODS AND RESULTS: This study consisted of
      272 patients with coronary artery disease not involving obstructive narrowing
      (>=50%) in the LAD. Patients underwent TTDE examination for CFR measurement in
      the LAD. During the follow-up period of 4.0+/-1.9 years, 32 patients (12%) had
      cardiovascular events. Cox proportional hazard analysis identified lower CFR as
      an independent risk factor of cardiovascular events (P<0.001), ACS events
      (P=0.008), and HF development (P=0.003). A CFR less than 2.4 was the best cut-off
      value for predicting all events (area under the curve=0.82). CFR excellently
      predicted the development of HF (area under the curve=0.95), but not ACS events
      (area under the curve=0.67). CONCLUSIONS: This TTDE study demonstrated that CFR
      was a significant and independent determinant of long-term cardiovascular events,
      ACS events and HF in patients with coronary artery disease. A CFR greater than
      2.0 was not suitable to predict a favorable long-term outcome, even in the
      absence of obstructive coronary narrowing.

PMID- 22640985
TI  - What type of statin and what level of low-density lipoprotein cholesterol should
      be appropriate for secondary prevention for Japanese patients with coronary
      artery disease?

PMID- 22640986
TI  - Ezetimibe improves endothelial function and inhibits Rho-kinase activity
      associated with inhibition of cholesterol absorption in humans.
AB  - BACKGROUND: Ezetimibe is an inhibitor of cholesterol absorption in the intestine.
      We examined whether ezetimibe improves endothelial function, and if so, what
      mechanisms are involved. METHODS AND RESULTS: Nineteen healthy subjects
      (male/female 14/5; mean age, 31+/-3 [SD] years-old) were randomized to receive
      ezetimibe (10mg/day) or pravastatin (10mg/day) for 4 weeks in a cross-over manner
      with a 4-week washout interval. Lipid profiles, flow-mediated dilatation (FMD)
      and Rho-kinase activity of circulating leukocytes (the extent of phosphorylation
      of myosin binding subunit, a Rho-kinase substrate) were examined. We also
      evaluated remnant-like particle cholesterol (RLP-C) known as an up-regulator of
      Rho-kinase and cholesterol absorption status by measuring cholestanol and
      campesterol/lathosterol ratio (CLR) (both absorption markers). Although ezetimibe
      and pravastatin equally reduced low-density lipoprotein cholesterol (E: -25% vs.
      P: -21%), the CLR was reduced by ezetimibe but was rather increased by
      pravastatin (E: -41% vs. P: +37%; P<0.01). Reduction in RLP-C by ezetimibe was
      greater compared with pravastatin (E: -33% vs. P: -14%; P<0.05). Importantly,
      ezetimibe significantly improved FMD (26%, P<0.05) and reduced Rho-kinase
      activity (-21%, P<0.05), whereas pravastatin had no such effects. A significant
      correlation was noted between the reduction in cholestanol and the improvement in
      FMD (P<0.05). CONCLUSIONS: These results indicate that ezetimibe improves
      endothelial function and inhibits Rho-kinase activity associated with the
      inhibition of cholesterol absorption, suggesting novel anti-atherogenic effects
      of the agent in humans.

PMID- 22640987
TI  - HLA-G and HLA-E specific mRNAs connote opposite prognostic significance in renal
      cell carcinoma.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is characterized by its resistance to
      radiotherapy and/or chemotherapy. On the other hand, it is an immunogenic tumor -
      it is able to stimulate antitumor responses. A prognostic significance of HLA-G
      expression by neoplastic cells in RCC is not well characterized; significance HLA
      E expression in RCC is not characterized at all. METHODS: In our study, we
      evaluated the expression of HLA-G and HLA-E specific mRNA transcripts produced by
      neoplastic cells in 38 cases of RCC and in 10 samples of normal kidney
      parenchyma. The results were statistically correlated with various clinico
      pathological parameters. RESULTS: We confirmed that HLA-G is downregulated in
      normal kidney tissue; if it is up-regulated in RCC, then it is connected to worse
      prognosis. On the other hand, HLA-E mRNA transcripts were present in both normal
      kidney tissue and RCC and their increasing concentrations counterintuitively
      carried better prognosis, more favorable pT stage and lower nuclear Fuhrmann's
      grade. CONCLUSION: Considering the fact that there is known aberrant activation
      of HLA-G and HLA-E expression by interferons, identification of HLA-G and HLA-E
      status could contribute to better selection of RCC patients who could possibly
      benefit from more tailored neoadjuvant biological/immunological therapy. Thus,
      these molecules could represent useful prognostic biomarkers in RCC, and the
      expression of both these molecules in RCC deserves further study. THE VIRTUAL:
      Slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/7383071387016614.

PMID- 22640989
TI  - Pds5 promotes cohesin acetylation and stable cohesin-chromosome interaction.
AB  - Pds5 and Wpl1 act as anti-establishment factors preventing sister-chromatid
      cohesion until counteracted in S-phase by the cohesin acetyl-transferase Eso1.
      However, Pds5 is also required to maintain sister-chromatid cohesion in G2. Here,
      we show that Pds5 is essential for cohesin acetylation by Eso1 and ensures the
      maintenance of cohesion by promoting a stable cohesin interaction with replicated
      chromosomes. The latter requires Eso1 only in the presence of Wapl, indicating
      that cohesin stabilization relies on Eso1 only to neutralize the anti
      establishment activity. We suggest that Eso1 requires Pds5 to counteract anti
      establishment. This allows both cohesion establishment and Pds5-dependent stable
      cohesin binding to chromosomes.

PMID- 22640988
TI  - The role of SH3BP2 in the pathophysiology of cherubism.
AB  - Cherubism is a rare bone dysplasia that is characterized by symmetrical bone
      resorption limited to the jaws. Bone lesions are filled with soft fibrous giant
      cell-rich tissue that can expand and cause severe facial deformity. The disorder
      typically begins in children at ages of 2-5 years and the bone resorption and
      facial swelling continues until puberty; in most cases the lesions regress
      spontaneously thereafter. Most patients with cherubism have germline mutations in
      the gene encoding SH3BP2, an adapter protein involved in adaptive and innate
      immune response signaling. A mouse model carrying a Pro416Arg mutation in SH3BP2
      develops osteopenia and expansile lytic lesions in bone and some soft tissue
      organs. In this review we discuss the genetics of cherubism, the biological
      functions of SH3BP2 and the analysis of the mouse model. The data suggest that
      the underlying cause for cherubism is a systemic autoinflammatory response to
      physiologic challenges despite the localized appearance of bone resorption and
      fibrous expansion to the jaws in humans.

PMID- 22640990
TI  - Hypothermia produces rat liver proteomic changes as in hibernating mammals but
      decreases endoplasmic reticulum chaperones.
AB  - Hypothermia is used in the clinic for protection of organs such as the brain
      against ischemic injury during aortic/complex congenital cardiac surgery or post
      resuscitation encephalopathy. The principal mechanism of hypothermic protection
      is suppression of metabolism, however, the pleiotropic effects of cooling are
      incompletely understood. Here, we used a rat model system to evaluate metabolic
      changes induced by deep hypothermia. The hypothermia-induced changes were
      identified using fluorescence-based two-dimensional (2-D) difference gel
      electrophoresis (DIGE) and matrix-assisted laser desorption/ionization-time-of
      flight (MALDI-TOF/TOF) tandem mass spectrometry. Rats were randomly assigned to a
      normothermic control group (37 degrees C, n=6) or hypothermia group (23 degrees
      C, n=6) that received surface cooling for 3h. Liver tissue was excised for
      assessment. Functional profiling of differently expressed proteins was performed
      as an enrichment analysis of Gene Ontology (GO) terms and pathways. We found that
      the livers of anesthetized rats with deep hypothermia showed significant
      downregulation of proteins in the endoplasmic reticulum and mitochondria, and of
      those involved in ATP binding, amino acid metabolism and urea cycle, response to
      oxidative stress, anti-apoptosis, negative regulation of apoptosis. The changes
      in the proteome of the hypothermic rats showed similarities, except with regard
      to endoplasmic reticulum chaperones, to those identified elsewhere in mammals
      undergoing hibernation.

PMID- 22640991
TI  - Specific micronutrient concentrations are associated with inflammatory cytokines
      in a rural population of Mexican women with a high prevalence of obesity.
AB  - It has been recognised recently that obese individuals have lower concentrations
      of micronutrients and this may affect the concentrations of inflammatory
      cytokines. A cross-sectional study was carried out to evaluate the association of
      specific micronutrients' status with chronic inflammation caused by obesity in
      280 women (36.1 (SD 7.5) years) from seven rural communities in Mexico.
      Measurements of weight, height and waist circumference were made on all women and
      body composition was determined by dual-energy X-ray absorptiometry.
      Concentrations of the cytokines IL-1, TNF-alpha, IL-6, IL-10 and IL-12, lipid
      profile, and the micronutrients Zn and vitamins A, C and E were determined in
      fasting blood samples. Ordered logistic regression models were used to determine
      associations between categorised cytokine levels and micronutrients. It was found
      that 80% of women were overweight or obese, and had significantly higher
      concentrations of C-reactive protein than normal-weight women (P= 0.05). The risk
      of higher levels of TNF-alpha, IL-6, IL-10 and IL-12 was reduced significantly
      among women with higher Zn concentrations (OR 0.63, 95% CI 0.42, 0.96, P= 0.03;
      OR 0.57, 95% CI 0.39, 0.86, P= 0.025; OR 0.63, 95% CI 0.41, 0.96, P= 0.04; OR
      0.62, 95% CI 0.41, 0.95, P= 0.03, respectively). Higher concentrations of vitamin
      A were slightly associated with reduced risks of higher levels of IL-1 and IL-12
      (OR 0.97, 95% CI 0.95, 0.99, P= 0.03; OR 0.97, 95% CI 0.94, 0.99, P= 0.03,
      respectively); when adjusting for BMI, this association was lost. No associations
      were found between vitamin C or vitamin E:lipids concentrations and inflammatory
      cytokines. In conclusion, higher Zn concentrations are associated with reduced
      risks of higher concentration of inflammation markers in a population of women
      with a high prevalence of obesity.

PMID- 22640992
TI  - Parasitology thanks the Referees of 2011.

PMID- 22640995
TI  - Growth and development: high early postnatal weight gain linked to adult
      metabolic syndrome.

PMID- 22640993
TI  - Getting blood from bone: an emerging understanding of the role that osteoblasts
      play in regulating hematopoietic stem cells within their niche.
AB  - Blood and bone are dynamic tissues that are continuously renewed throughout life.
      Early observations based upon the proximity of bone and hematopoietic progenitor
      populations in marrow suggested that interactions between skeletal and
      hematopoietic elements are likely to be crucial in the development and function
      of each system. As a result of these morphologic observations, several groups
      have demonstrated that the osteoblasts play an important role in hematopoiesis by
      serving as a specific local microenvironment, or niche, for hematopoietic stem
      cells. Significant new developments in this area of active investigation have
      emerged since our last examination of this area in 2005. Here we discuss these
      new insights into the function and morphology of the hematopoietic stem cell
      niche, with a particular focus on cells of the osteoblastic lineage.

PMID- 22640996
TI  - Nutrition: D-iabetes and D-eath D-efying vitamin D.

PMID- 22640994
TI  - How insights from cardiovascular developmental biology have impacted the care of
      infants and children with congenital heart disease.
AB  - To illustrate the impact developmental biology and genetics have already had on
      the clinical management of the million infants born worldwide each year with CHD,
      we have chosen three stories which have had particular relevance for pediatric
      cardiologists, cardiothoracic surgeons, cardiac anesthesiologists, and cardiac
      nurses. First, we show how Margaret Kirby's finding of the unexpected
      contribution of an ectodermal cell population - the cranial neural crest - to the
      aortic arch arteries and arterial pole of the embryonic avian heart provided a
      key impetus to the field of cardiovascular patterning. Recognition that a
      majority of patients affected by the neurocristopathy DiGeorge syndrome have a
      chromosome 22q11 deletion, have also spurred tremendous efforts to characterize
      the molecular mechanisms contributing to this pathology, assigning a major role
      to the transcription factor Tbx1. Second, synthesizing the work of the last two
      decades by many laboratories on a wide gamut of metazoans (invertebrates,
      tunicates, agnathans, teleosts, lungfish, amphibians, and amniotes), we review
      the >20 major modifications and additions to the ancient circulatory arrangement
      composed solely of a unicameral (one-chambered), contractile myocardial tube and
      a short proximal aorta. Two changes will be discussed in detail - the
      interposition of a second cardiac chamber in the circulation and the septation of
      the cardiac ventricle. By comparing the developmental genetic data of several
      model organisms, we can better understand the origin of the various components of
      the multicameral (multi-chambered) heart seen in humans. Third, Martina
      Brueckner's discovery that a faulty axonemal dynein was responsible for the
      phenotype of the iv/iv mouse (the first mammalian model of human heterotaxy)
      focused attention on the biology of cilia. We discuss how even the care of the
      complex cardiac and non-cardiac anomalies seen in heterotaxy syndrome, which have
      long seemed impervious to advancements in surgical and medical intensive care,
      may yet yield to strategies grounded in a better understanding of the cilium. The
      fact that all cardiac defects seen in patients with full-blown heterotaxy can
      also be seen in patients without obvious laterality defects hints at important
      roles for ciliary function not only in left-right axis specification but also in
      cardiovascular morphogenesis. These three developmental biology stories
      illustrate how the remaining unexplained mortality and morbidity of congenital
      heart disease can be solved.

PMID- 22640997
TI  - Bone: impact loading-nature's way to strengthen bone.

PMID- 22641001
TI  - Thyroid function: low T4 levels a risk factor for fatty liver?

PMID- 22641000
TI  - The role of Klotho in energy metabolism.
AB  - A disproportionate expansion of white adipose tissue and abnormal recruitment of
      adipogenic precursor cells can not only lead to obesity but also impair glucose
      metabolism, which are both common causes of insulin resistance and diabetes
      mellitus. The development of novel and effective therapeutic strategies to slow
      the progression of obesity, diabetes mellitus and their associated complications
      will require improved understanding of adipogenesis and glucose metabolism.
      Klotho might have a role in adipocyte maturation and systemic glucose metabolism.
      Klotho increases adipocyte differentiation in vitro, and mice that lack Klotho
      activity are lean owing to reduced white adipose tissue accumulation; moreover,
      mice that lack the Kl gene (which encodes Klotho) are resistant to obesity
      induced by a high-fat diet. Knockout of Kl in leptin-deficient Lep(ob/ob) mice
      reduces obesity and increases insulin sensitivity, which lowers blood glucose
      levels. Energy metabolism might also be influenced by Klotho. However, further
      studies are needed to explore the possibility that Klotho could be a novel
      therapeutic target to reduce obesity and related complications, and to determine
      whether and how Klotho might influence the regulation and function of a related
      protein, beta-Klotho, which is also involved in energy metabolism.

PMID- 22641002
TI  - Thyroid function: optimizing molecular testing in thyroid nodule cytology.

PMID- 22641003
TI  - Diabetes: regional variation in lower limb amputation incidence.

PMID- 22641005
TI  - Comparison of salivary cortisol as measured by different immunoassays and tandem
      mass spectrometry.
AB  - Assessing the amount of bioavailable cortisol in saliva with immunoassays and
      thus sampling an endocrine marker of hypothalamus-pituitary-adrenal axis activity
      is of major interest in both research and clinical practice. However, absolute
      cortisol concentrations obtained with different immunoassays (IAs) are barely
      comparable precluding direct comparison between studies or individuals whenever
      cortisol analyses were not based on the same IA. The present technical report
      aims to solve this problem by evaluating the validity of, as well as agreement
      between the most commonly used immunoassays in psychoneuroendocrinological
      research (i.e., IBL, DRG, Salimetrics, DSL, and DELFIA) and a reference method
      (LC-MS/MS) in a sample of 195 saliva specimen covering the whole range of
      cortisol concentrations in adults. A structural equation modelling framework is
      applied to decompose systematic assay variance and estimate cortisol reference
      values, which are adjusted for measurement error and interference of salivary
      cortisone. Our findings reveal nonlinear relations between IAs and LC-MS/MS,
      which are discussed in terms of IA cross-reactivity with saliva matrix
      components. Finally guidelines for converting cortisol concentrations being
      obtained by these immunoassays into comparable reference values are proposed by
      providing conversion functions, a conversion table, and an online conversion
      tool.

PMID- 22641007
TI  - Lattice dynamics of FeSb2.
AB  - The lattice dynamics of FeSb(2) is investigated by first-principles density
      functional theory calculations and Raman spectroscopy. All Raman- and infrared
      active phonon modes are properly assigned. The calculated and measured phonon
      energies are in good agreement. We have observed strong mixing of the A(g)
      symmetry modes, with the intensity exchange in the temperature range 210 and 260
      K. The A(g) mode repulsion increases by doping FeSb(2) with Co, with no
      signatures of the electron-phonon interaction for these modes.

PMID- 22641006
TI  - Fkbp52 heterozygosity alters behavioral, endocrine and neurogenetic parameters
      under basal and chronic stress conditions in mice.
AB  - Aversive life events represent one of the main risk factors for the development
      of many psychiatric diseases, but the interplay between environmental factors and
      genetic predispositions is still poorly understood. One major finding in many
      depressed patients is an impaired regulation of the hypothalamic-pituitary
      adrenal (HPA) axis. The negative feedback loop of the HPA axis is mediated via
      the glucocorticoid receptor (GR) and the mineralocorticoid receptor. The co
      chaperones FK506-binding protein 51 (FKBP51) and FK506-binding protein 52
      (FKBP52) are components of the heat shock protein 90-receptor-heterocomplex and
      are functionally divergent regulators of both receptors. Here, we characterized
      heterozygous Fkbp52 knockout (Fkbp52(+/-)) mice under basal or chronic social
      defeat stress (CSDS) conditions with regard to physiological, neuroendocrine,
      behavioral and mRNA expression alterations. Fkbp52(+/-) mice displayed symptoms
      of increased stress sensitivity in a subset of behavioral and neuroendocrine
      parameters. These included increased anxiety-related behavior in the elevated
      plus-maze and an enhanced neuroendocrine response to a forced swim test (FST),
      possibly mediated by reduced GR sensitivity. At the same time, Fkbp52(+/-) mice
      also demonstrated signs of stress resilience in other behavioral and
      neuroendocrine aspects, such as reduced basal corticosterone levels and more
      active stress-coping behavior in the FST following CSDS. These contrasting
      results are in line with previous reports showing that FKBP52 is not involved in
      all branches of GR signaling, but rather acts in a gene-specific manner to
      regulate GR transcriptional activation.

PMID- 22641008
TI  - Highly sensitive and selective trimethylamine sensor using one-dimensional ZnO
      Cr2O3 hetero-nanostructures.
AB  - Highly selective and sensitive detection of trimethylamine (TMA) was achieved by
      the decoration of discrete p-type Cr(2)O(3) nanoparticles on n-type ZnO nanowire
      (NW) networks. Semielliptical Cr(2)O(3) nanoparticles with lateral widths of 3-8
      nm were deposited on ZnO NWs by the thermal evaporation of CrCl(2) at 630 
      degrees C, while a continuous Cr(2)O(3) shell layer with a thickness of 30-40 nm
      was uniformly coated on ZnO NWs at 670  degrees C. The response (R(a)/R(g): R(a),
      resistance in air; R(g), resistance in gas) to 5 ppm TMA of Cr(2)O(3)-decorated
      ZnO NWs was 17.8 at 400  degrees C, which was 2.4 times higher than that to 5 ppm
      C(2)H(5)OH and 4.3-8.4 times higher than those to 5 ppm p-xylene, NH(3), benzene,
      C(3)H(8), toluene, CO, and H(2). In contrast, both pristine ZnO and ZnO (core)
      Cr(2)O(3) (shell) nanocables (NCs) showed comparable responses to the different
      gases. The highly selective and sensitive detection of TMA that was achieved by
      the deposition of semielliptical Cr(2)O(3) nanoparticles on ZnO NW networks was
      explained by the catalytic effect of Cr(2)O(3) and the extension of the electron
      depletion layer via the formation of p-n junctions.

PMID- 22641009
TI  - Decreased RNA expression of interleukin 17A in skin of leprosy.
AB  - Interleukin-17A (IL-17A) is a proinflamatory cytokine that plays an important
      role in fighting pathogens at mucosal interfaces, by summoning neutrophils and
      upregulating cytoplasmatic antimicrobial peptides. So far, the presence of IL-17A
      in leprosy has not been demonstrated. The expression of IL-17A and related
      cytokines (IL-6 and IL-23p19) was addressed through RNA extraction and cDNA
      quantitative amplification in macerated biopsies of active lesions of 48 leprosy
      patients and 20 fragments of normal skin of individuals. Blood levels of IL-17A,
      IL-23p19 and IL-6 were determined by ELISA. We found an abrogated mRNA IL-17A
      response in all biopsies of leprosy patients, as compared with controls.
      Circulating IL-17A and IL-23p19 were undetectable in both patients and controls,
      but IL-6 was higher in lepromatous patients. Although at low levels, IL-17A mRNA
      in lepromatous patients had an inverse linear correlation with bacillary burden.
      Low expression of IL-17A in patients may be a constitutive genetic feature of
      leprosy patients or a circumstantial event induced by the local presence of the
      pathogen, as an escape mechanism.

PMID- 22641010
TI  - Plasmonic surface enhancement of dual fluorescence and phosphorescence emission
      from organic semiconductors: effect of exchange gap and spin-orbit coupling.
AB  - Dual singlet-triplet fluorescence-phosphorescence emitting compounds demonstrate
      that plasmonic surface enhancement is controlled solely by the underlying
      oscillator strength of a transition: metal-free compounds with weak spin-orbit
      coupling show no enhancement in phosphorescence efficiency even though
      fluorescence is amplified.

PMID- 22641011
TI  - Parallels between neuron and lens fiber cell structure and molecular regulatory
      networks.
AB  - Studies over the past fifty years have identified extensive similarities between
      neurons and elongated fiber cells that make up in the interior of the ocular
      lens. Electron micrographs showed parallels in the organization of their
      intracellular vesicle transport machinery and between lens fiber cell lateral
      protrusions and dendritic spines. Consistent with those observations, a number of
      gene products first characterized as highly neuron-preferred in their expression
      were also demonstrated in lens fiber cells. Going further, a fundamental network
      of regulatory factors with critical roles in determining the neuronal phenotype
      were also identified in lenses, and showed a corresponding mutually exclusive
      distribution of neural and non-neural factor isoforms in mitotic lens epithelial
      cells and post-mitotic fiber cells consistent with their interlocking functions
      in neural cells. These included REST/NRSF transcription factors, members of major
      RNA binding protein families, and "brain-specific" miRNAs that were each shown to
      have global roles in governing neural and non-neural gene expression and
      alternative transcript splicing in vertebrates. This review discusses these
      extensive parallels between neurons and fiber cells and implications regarding
      common themes in lens and neural cell physiology and disease, which may also
      suggest related evolutionary processes.

PMID- 22641012
TI  - Regional differences in BMP-dependence of dorsoventral patterning in the leech
      Helobdella.
AB  - In the leech Helobdella, the ectoderm exhibits a high degree of morphological
      homonomy between body segments, but pattern elements in lateral ectoderm arise
      via distinct cell lineages in the segments of the rostral and midbody regions. In
      each of the four rostral segments, a complete set of ventrolateral (O fate) and
      dorsolateral (P fate) ectodermal pattern elements arises from a single founder
      cell, op. In the 28 midbody and caudal segments, however, there are two initially
      indeterminate o/p founder cells; the more dorsal of these is induced to adopt the
      P fate by BMP5-8 emanating from the dorsalmost ectoderm, while the more ventral
      cell assumes the O fate. Previous work has suggested that the dorsoventral
      patterning of O and P fates differs in the rostral region, but the role of BMP
      signaling in those segments has not been investigated. We show here that
      suppression of dorsal BMP5-8 signaling (which effects a P-to-O fate change in the
      midbody) has no effect on the patterning of O and P fates in the rostral region.
      Furthermore, ectopic expression of BMP5-8 in the ventral ectoderm (which induces
      an O-to-P fate change in the midbody) has no effect in the rostral region.
      Finally, expression of a dominant-negative BMP receptor (which induces a P-to-O
      fate change in the midbody) fails to affect O/P patterning in the rostral region.
      Thus, the rostral segments appear to use some mechanism other than BMP signaling
      to pattern O and P cell fates along the dorsoventral axis. From a mechanistic
      standpoint, the OP lineage of the rostral segments and the O-P equivalence group
      of the midbody and caudal segments constitute distinct developmental modules that
      rely to differing degrees on positional cues from surrounding ectoderm in order
      to specify homonomous cell fates.

PMID- 22641014
TI  - Role of Neurokinin B and Dynorphin A in pituitary gonadotroph and
      somatolactotroph cell lines.
AB  - The role of Neurokinin B (NKB) and Dynorphin A (Dyn) in the regulation of the
      hypothalamic pituitary axis is an important area of recent investigation.  These
      peptides are critical for the rhythmic release of GnRH, which subsequently
      stimulates the secretion of the gonadotropins, luteinizing hormone (LH) and
      follicle-stimulating hormone (FSH).  The present study utilized the gonadotroph
      cell line LbetaT2 and the somatolactotroph GH3 cell line to examine the possible
      role of these peptides in pituitary hormone secretion.  The NKB receptor (NK3R)
      and the Dyn receptor (the kappa-opiate receptor (KOR)) were both detected in
      LbetaT2 cells and GH3 cells.  NKB, by itself, failed to increase gonadotropin
      LHbeta and FSHbeta promoter activities and did not modulate the effects of GnRH
      on gonadotropin promoter activity.  In GH3 cells, NKB significantly increased TRH
      induced PRL promoter activity although NKB alone did not have an effect on basal
      PRL promoter activity.  Dyn had no effect on gonadotropin promoters alone or in
      combination with GnRH stimulation.  PRL promoters stimulated by TRH were not
      significantly changed by Dyn.  TRH-induced PRL promoter activity was further
      increased in the presence of higher concentrations of NKB, whereas Dyn did not
      have a significant effect on the PRL promoter even at a high concentration.  In
      addition, TRH-induced ERK (Extracelluar signal-regulated kinase) activation was
      enhanced in the presence of NKB.  Our current study demonstrated that NKB had a
      stimulatory effect on PRL expression in a PRL-producing cell, but had no effect
      on gonadotropin secretion from a gonadotroph cell line.

PMID- 22641013
TI  - Subfunctionalization and neofunctionalization of vertebrate Lef/Tcf transcription
      factors.
AB  - Invertebrates express a multitude of Wnt ligands and all Wnt/beta-catenin
      signaling pathways converge to only one nuclear Lef/Tcf. In vertebrates, however,
      four distinct Lef/Tcfs, i.e. Tcf-1, Lef, Tcf-3, and Tcf-4 fulfill this function.
      At present, it is largely unknown to what extent the various Lef/Tcfs are
      functionally similar or diversified in vertebrates. In particular, it is not
      known which domains are responsible for the Tcf subtype specific functions. We
      investigated the conserved and non-conserved functions of the various Tcfs by
      using Xenopus laevis as a model organism and testing Tcfs from Hydra
      magnipapillata, Caenorhabditis elegans and Drosophila melanogaster. In order to
      identify domains relevant for the individual properties we created series of
      chimeric constructs consisting of parts of XTcf-3, XTcf-1 and HyTcf. Rescue
      experiments in Xenopus morphants revealed that the three invertebrate Tcfs tested
      compensated the loss of distinct Xenopus Tcfs: Drosophila Tcf (Pangolin) can
      substitute for the loss of XTcf-1, XTcf-3 and XTcf-4. By comparison,
      Caenorhabditis Tcf (Pop-1) and Hydra Tcf (HyTcf) can substitute for the loss of
      only XTcf-3 and XTcf-4, respectively. The domain, which is responsible for
      subtype specific functions is the regulatory CRD domain. A phylogenetic analysis
      separates Tcf-1/Lef-1 from the sister group Tcf-3/4 in the vertebrate lineage. We
      propose that the vertebrate specific diversification of Tcfs in vertebrates
      resulted in subfunctionalization of a Tcf that already united most of the Lef/Tcf
      functions.

PMID- 22641015
TI  - A common theory for phase-modulated homonuclear decoupling in solid-state NMR.
AB  - We propose a new framework for homonuclear dipolar decoupling in solid-state NMR
      that provides a theoretical link between the FSLG, PMLG and DUMBO families. We
      show that through the use of a Legendre polynomial basis, the phase modulation of
      these decoupling schemes can be described by the same set of parameters,
      permitting for the first time a direct theoretical comparison between these
      methods. Use of this common basis reveals that the central decoupling mechanism
      is the same for DUMBO and FSLG/PMLG and that a similar vector picture can be used
      to describe both methods. In addition to the common root of decoupling
      efficiency, this new analysis highlights two major points of difference between
      the methods. First, the DUMBO phase modulation consists not only of a linear
      change in phase with time a la PMLG but also smaller high-order oscillations,
      which act to improve line-narrowing performance. Second, we show how the DUMBO
      phase waveforms are generated from a four-step permutation of a single asymmetric
      unit, in contrast to the two-step permutation of PMLG. Numerical simulations and
      experimental results suggest that this latter point of difference is responsible
      for the superior performance of DUMBO in the presence of significant RF
      inhomogeneity.

PMID- 22641016
TI  - Howard Green. Interview by Darren Burgess.

PMID- 22641017
TI  - Gene expression: More roles and details for polymerase pausing.

PMID- 22641019
TI  - Extracellular loop 2 in the FSH receptor is crucial for ligand mediated receptor
      activation.
AB  - The present study aims to determine the role of the specific residues of the
      extracellular loops (ELs) of the FSH receptor (FSHR) in hormone binding and
      receptor activation. By substituting the sequences of each of the ELs of human
      FSHR with those of the luteinizing hormone/choriogonadotropin receptor (LH/CGR),
      we generated three mutant constructs where the three ELs were individually
      replaced. A fourth construct had all the three substituted ELs. The receptor
      expression and hormone binding ability of the mutants were comparable to that of
      the wild type. Hormone-induced signaling and internalization were lower in the
      EL2 substitution mutant (EL2M). In this mutant, the EL2 of FSHR was substituted
      with the corresponding loop of LH/CGR. Interestingly, homology modeling revealed
      a change in the orientation of EL2 in the mutant receptor. Thus, disruption of
      EL2 affected overall receptor function, suggesting the role of FSHR specific
      residues of the loop in ligand mediated signaling.

PMID- 22641020
TI  - SDH, CCO and PKCalpha are the direct targets of aconitine?

PMID- 22641018
TI  - Functions of DNA methylation: islands, start sites, gene bodies and beyond.
AB  - DNA methylation is frequently described as a 'silencing' epigenetic mark, and
      indeed this function of 5-methylcytosine was originally proposed in the 1970s.
      Now, thanks to improved genome-scale mapping of methylation, we can evaluate DNA
      methylation in different genomic contexts: transcriptional start sites with or
      without CpG islands, in gene bodies, at regulatory elements and at repeat
      sequences. The emerging picture is that the function of DNA methylation seems to
      vary with context, and the relationship between DNA methylation and transcription
      is more nuanced than we realized at first. Improving our understanding of the
      functions of DNA methylation is necessary for interpreting changes in this mark
      that are observed in diseases such as cancer.

PMID- 22641021
TI  - L-DOPA induced-endogenous 6-hydroxydopamine is the cause of aggravated
      dopaminergic neurodegeneration in Parkinson's disease patients.
AB  - Dopamine replacement therapy by 3,4-dihydroxyphenylalanine (L-DOPA), which is the
      gold standard symptomatic treatment for the Parkinson's disease (PD), frequently
      leads to potential debilitating side-effects such as dyskinesia. One of the most
      significant molecules reported to be produced endogenously in the brain is 6
      hydroxydopamine (6-OHDA), contributed solely by unsequestered dopamine in neurons
      derived from L-DOPA. It is further demonstrated that scavengers of hydroxyl
      radicals such as melatonin and salicylic acid inhibited its generation. However
      no reports on the level of 6-OHDA and hydroxyl radicals generated in vivo in
      human brain is known. Oxidative stress and mitochondrial dysfunction are known to
      be associated with Lewy body formation, which is directly dependent on the levels
      of free dopamine. Therefore, it is hypothesized that L-DOPA induced increase in
      endogenous 6-OHDA levels will have the ability to cause oxidative stress and
      mitochondrial dysfunctions that eventually leads to Lewy body formation in
      dopaminergic neurons resulting in its degeneration. Concomitant use of potent
      anti-oxidants along with L-DOPA would help in attenuating the neurodegeneration
      caused by endogenous 6-OHDA and would ultimately delay the progression of PD.

PMID- 22641022
TI  - An energy-failure based brain edema concept.
AB  - Brain edema concepts comprised interstitial, cytotoxic and vasogenic edema as
      three separate concepts. This is a theory of initiation of brain edema genesis
      arising from the neuron's cellular metabolism on the basis of energy failure by
      relative hyperglycolysis and resulting lactacidosis. It can describe edema
      genesis in trauma, hemorrhage, stroke and infections.

PMID- 22641023
TI  - Preparation, characterization, and induction of cell apoptosis of cocoa
      procyanidins-gelatin-chitosan nanoparticles.
AB  - Cocoa procyanidins (CPs)-gelatin-chitosan nanoparticles were fabricated based on
      the procyanidin-protein and electrostatic interactions, with an objective to
      enhance the stability and bioactivity of CPs. The CPs were purified using
      chromatographic methods and analyzed using HPLC equipped with a fluorescence
      detector (FLD) and mass spectrometer (MS). The purified CPs had a purity of 53.1%
      (w/w) and contained procyanidin oligomers (from monomer to decamers) and
      polymers, with polymers being the predominant component (26.4%, w/w). Different
      CPs-gelatin-chitosan mass ratios were tested to investigate the effects of
      formulation on the nanoparticle fabrication. Using CPs-gelatin-chitosan mass
      ratio of 0.75:1:0.5, the resultant nanoparticles had a particle size of 344.7 nm,
      zeta-potential of +29.8 mV, particle yield of 51.4%, loading efficiency of 50.1%,
      and loading capacity of 20.5%. The CPs-gelatin-chitosan nanoparticles were
      spherical as observed by scanning electron microscopy (SEM). Fourier transform
      infrared spectroscopy (FTIR) suggested that the primary interaction between the
      CPs and gelatin was hydrogen bond and hydrophobic interaction, while
      electrostatic interaction was the main binding force between chitosan and CPs
      gelatin nanoparticles. Nanoencapsulation of the CPs significantly improved the
      stability of the CPs at 60 degrees C. The CPs-gelatin-chitosan nanoparticles
      showed the same apoptotic effects at lower concentrations in human acute
      monocytic leukemia THP-1 cells compared with the CPs in solution.

PMID- 22641024
TI  - Vacancies in GaN bulk and nanowires: effect of self-interaction corrections.
AB  - We investigate gallium and nitrogen vacancies in gallium nitride (GaN) bulk and
      nanowires using self-interaction corrected pseudopotentials (SIC). In particular,
      we examine the band structures to compare and contrast differences between the
      SIC results and standard density functional theory (DFT) results using a
      generalized gradient approximation (GGA) (Perdew et al 1996 Phys. Rev. Lett. 77
      3865) functional. For pure nanowires, we observed similar trends in the bandgap
      behaviour, with the gap decreasing for increasing nanowire diameters (with larger
      bandgaps using SIC pseudopotentials). For gallium vacancies in bulk GaN and GaN
      nanowires, SIC results are similar to DFT-GGA results, albeit with larger
      bandgaps. Nitrogen vacancies in bulk GaN show similar defect-induced states near
      the conduction band, whilst a lower lying defect state is observed below the
      valence band for the DFT-GGA calculations and above the valence band for the SIC
      results. For nitrogen vacancies in GaN nanowires, similar defect states are
      observed near the conduction band, however, while the SIC calculations also show
      a defect state/s above the valence band, we were unable to locate this state for
      the DFT-GGA calculations (possibly because it is hybridized with edge states and
      buried below the valence band).

PMID- 22641025
TI  - Mincle polarizes human monocyte and neutrophil responses to Candida albicans.
AB  - The distribution and function of the C-type lectin Mincle has not previously been
      investigated in human cells, although mouse models have demonstrated a non
      redundant role for Mincle in the host response to fungal infections. This study
      identified an unusual pattern of reciprocal expression of Mincle on peripheral
      blood monocytes or neutrophils isolated from the same donor. Expression on
      monocytes was inversely correlated with phagocytosis and yeast killing, but was
      necessary for the induction of inflammatory cytokines in response to ex vivo
      Candida challenge. In contrast, Mincle expression on neutrophils was associated
      with phagocytic and candidacidal potential of those cells. Candida challenge
      upregulated Mincle expression but only in Mincle+ cells. These data highlight
      species-specific differences between the regulation of Mincle expression in mouse
      and man. Reciprocal expression of Mincle modified the candidacidal potential of
      monocytes or neutrophils, suggesting it may also polarize the type of host
      response to fungal infection.

PMID- 22641027
TI  - Neurological toxicity after phenytoin infusion in a pediatric patient with
      epilepsy: influence of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms.
AB  - Pharmacogenetic studies have shown that genetic defects in drug-metabolizing
      enzymes encoded by CYP2C9, CYP2C19 genes and by the transporter ABCB1 gene can
      influence phenytoin (PTH) plasma levels and toxicity. The patient reported here
      is a 2-year-old girl with a medical history of cryptogenic (probably symptomatic)
      epilepsy, who had her first focal seizure with secondary generalization at 13
      months of age. She initially received oral valproate treatment and three months
      later, she was prescribed an oral oxcarbazepine treatment. At 20 months of age,
      she was admitted to the Emergency Department because of generalized convulsive
      Status Epilepticus needing to be immediately treated with rectal diazepam (0.5 mg
      kg(-1)), intravenous diazepam (0.3 mg kg(-1)), and intravenous phenytoin with an
      initial-loading dose of 15 mg kg(-1). However, two hours after the initial
      loading dose of PTH, the patient developed dizziness, nystagmus, ataxia and
      excessive sedation. Other potential causes of PTH toxicity were excluded such as
      drug interactions, decreased albumin or lab error. Therefore, to explain the
      neurological toxicity, PTH plasma levels and CYP2C9, CYP2C19 and ABCB1 genetic
      polymorphisms were analyzed. Initial plasma PTH levels were higher than expected
      (69 mg l(-1); normal range: 10-20 mg l(-1)), and the patient was homozygous for
      the CYP2C9*2 allele, heterozygous for the CYP2C19*4 allele and homozygous for the
      3435C and 1236C ABCB1 alleles. Present findings support the previously
      established relationship between CYP2C9 and CYP2C19 genetic polymorphisms and the
      increased risk to develop PTH toxicity owing to high plasma concentrations.
      Nevertheless, although the association of these genes with PTH-induced adverse
      effects has been well-documented in adult populations, this is the first report
      examining the influence of these genetic polymorphisms on PTH plasma levels and
      toxicity in a pediatric patient. 

PMID- 22641026
TI  - Predicting inhaled corticosteroid response in asthma with two associated SNPs.
AB  - Inhaled corticosteroids (ICS) are the most commonly used controller medications
      prescribed for asthma. Two single-nucleotide polymorphisms (SNPs), rs1876828 in
      corticotrophin releasing hormone receptor 1 and rs37973 in GLCCI1, have
      previously been associated with corticosteroid efficacy. We studied data from
      four existing clinical trials of asthmatics, who received ICS and had lung
      function measured by forced expiratory volume in 1 s (FEV1) before and after the
      period of such treatment. We combined the two SNPs rs37973 and rs1876828 into a
      predictive test of FEV1 change using a Bayesian model, which identified patients
      with good or poor steroid response (highest or lowest quartile, respectively)
      with predictive performance of 65.7% (P=0.039 vs random) area under the receiver
      operator characteristic curve in the training population and 65.9% (P=0.025 vs
      random) in the test population. These findings show that two genetic variants can
      be combined into a predictive test that achieves similar accuracy and superior
      replicability compared with single SNP predictors. 

PMID- 22641028
TI  - ABCB1 gene variants influence tolerance to selective serotonin reuptake
      inhibitors in a large sample of Dutch cases with major depressive disorder.
AB  - P-glycoprotein (P-gp), an ATP-driven efflux pump in the blood-brain barrier, has
      a major impact on the delivery of antidepressant drugs in the brain. Genetic
      variants in the gene ABCB1 encoding for P-gp have inconsistently been associated
      with adverse effects. In order to resolve these inconsistencies, we conducted a
      study in a large cohort of patients with major depressive disorder with the aim
      to unravel the association of ABCB1 variants with adverse effects of
      antidepressants and in particular with selective serotonin reuptake inhibitors
      (SSRIs), which display affinity as substrate for P-gp. The Netherlands Study of
      Depression and Anxiety (NESDA) study was used as a clinical sample. For 424
      patients data were available on drug use, side effects. We selected six ABCB1
      gene variants (1236T>C, 2677G>T/A, 3435T>C, rs2032583, rs2235040 and rs2235015)
      and analyzed them for association with adverse drug effects using multinomial
      regression analysis for both single variants and haplotypes. We found a
      significant association between the number of SSRI-related adverse drug effects
      and rs2032583 (P=0.001), rs2235040 (P=0.002) and a haplotype (P=0.002). Moreover,
      serotonergic effects (sleeplessness, gastrointestinal complaints and sexual
      effects) were significantly predicted by these variants and haplotype
      (P=0.002/0.003). We conclude that adverse drug effects with SSRI treatment, in
      particular serotonergic effects, are predicted by two common polymorphisms of the
      ABCB1 gene. 

PMID- 22641029
TI  - Particle-assisted Ga(x)In(1-x)P nanowire growth for designed bandgap structures.
AB  - Non-tapered vertically straight Ga(x)In(1-x)P nanowires were grown in a
      compositional range from Ga(0.2)In(0.8)P to pure GaP in particle-assisted mode by
      controlling the trimethylindium, trimethylgallium and hydrogen chloride flows in
      metal-organic vapor phase epitaxy. X-ray energy dispersive spectroscopy in
      transmission electron microscopy revealed homogeneous radial material composition
      in single nanowires, whereas variations in the material composition were found
      along the nanowires. High-resolution x-ray diffraction indicates a variation of
      the material composition on the order of about 19% measuring an entire sample
      area, i.e., including edge effects during growth. The non-capped nanowires emit
      room temperature photoluminescence strongly in the energy range of 1.43-2.16 eV,
      correlated with the bandgap expected from the material composition.

PMID- 22641030
TI  - Primary mucinous carcinoma of the skin arising from an in situ component.

PMID- 22641032
TI  - Insights in small Heat Shock Protein/client interaction by combined protection
      analysis of two different client proteins.
AB  - sHSPs interact with clients under denaturing conditions. CPH1Delta2, a truncated
      version of cyanobacterial phytochrome CPH1, was introduced as a new reporter
      (client). Comparative analyses of At17.8 and At17.6B as cytosolic class I sHSP
      representatives demonstrated the advantages of a chromophore-bearing
      photoreversible protein as new client for analyzing sHSP holdase function in
      addition to malate dehydrogenase (MDH). The tested sHSPs protected both clients
      in similar ways but with different efficiencies. Bis-ANS binding studies with
      sHSPs suggested that the bis-ANS binding is dependent on interactions between
      different sHSPs and MDH under denaturing temperatures.

PMID- 22641031
TI  - Induction of epithelial-mesenchymal transition with O-glycosylated oncofetal
      fibronectin.
AB  - Epithelial-mesenchymal transition (EMT) has been shown to play a key role in
      embryogenesis and cancer progression. We previously found that fibronectin (FN)
      carrying O-GalNAc at a specific site is selectively expressed in cancer and fetal
      cells/tissues, and termed oncofetal FN (onfFN). Here, we show that (i) a newly
      established monoclonal antibody against FN lacking the O-GalNAc, termed normalFN
      (norFN), is useful for isolation of onfFN, (ii) onfFN, but not norFN, can induce
      EMT in human lung carcinoma cells, (iii) onfFN has a synergistic effect with
      transforming growth factor (TGF)beta1 in EMT induction.

PMID- 22641033
TI  - Rat CYP2D2, not 2D1, is functionally conserved with human CYP2D6 in endogenous
      morphine formation.
AB  - The assumption that CYP2D1 is the corresponding rat cytochrome to human CYP2D6
      has been revisited using recombinant proteins in direct enzyme assays. CYP2D1 and
      2D2 were incubated with known CYP2D6 substrates, the three morphine precursors
      thebaine, codeine and (R)-reticuline. Mass spectrometric analysis showed that rat
      CYP2D2, not 2D1, catalyzed the 3-O-demethylation reaction of thebaine and
      codeine. In addition, CYP2D2 incubated with (R)-reticuline generated four
      products corytuberine, pallidine, salutaridine and isoboldine while rat CYP2D1
      was completely inactive. This intramolecular phenol-coupling reaction follows the
      same mechanism as observed for CYP2D6. Michaelis-Menten kinetic parameters
      revealed high catalytic efficiencies for rat CYP2D2. These findings suggest a
      critical evaluation of other commonly accepted, however untested, CYP2D1
      substrates.

PMID- 22641035
TI  - The NRF2-related interactome and regulome contain multifunctional proteins and
      fine-tuned autoregulatory loops.
AB  - NRF2 is a well-known, master transcription factor (TF) of oxidative and
      xenobiotic stress responses. Recent studies uncovered an even wider regulatory
      role of NRF2 influencing carcinogenesis, inflammation and neurodegeneration.
      Prompted by these advances here we present a systems-level resource for NRF2
      interactome and regulome that includes 289 protein-protein, 7469 TF-DNA and 85
      miRNA interactions. As systems-level examples of NRF2-related signaling we
      identified regulatory loops of NRF2 interacting proteins (e.g., JNK1 and CBP) and
      a fine-tuned regulatory system, where 35 TFs regulated by NRF2 influence 63
      miRNAs that down-regulate NRF2. The presented network and the uncovered
      regulatory loops may facilitate the development of efficient, NRF2-based
      therapeutic agents.

PMID- 22641034
TI  - Structural recognition mechanisms between human Src homology domain 3 (SH3) and
      ALG-2-interacting protein X (Alix).
AB  - The functions of Src family kinases are tightly regulated through Src homology
      (SH) domain-mediated protein-protein interactions. We previously reported the
      biophysical characteristics of the apoptosis-linked gene 2-interacting protein X
      (Alix) in complex with the haemopoietic cell kinase (Hck) SH3 domain. In the
      current study, we have combined ITC, NMR, SAXS and molecular modeling to
      determine a 3D model of the complex. We demonstrate that Hck SH3 recognizes an
      extended linear proline-rich region of Alix. This particular binding mode enables
      Hck SH3 to sense a specific non-canonical residue situated in the SH3 RT-loop of
      the kinase. The resulting model helps clarify the mechanistic insights of Alix
      Hck interaction.

PMID- 22641036
TI  - Trypanosomes contain two highly different isoforms of peroxin PEX13 involved in
      glycosome biogenesis.
AB  - We previously identified the peroxin PEX13 in Trypanosoma brucei. Although
      lacking some features considered typical of PEX13s, it appeared functional in the
      biogenesis of glycosomes, the peroxisome-like organelles of trypanosomatids. Here
      we report the identification of a very different trypanosomatid PEX13, not
      containing the commonly encountered PEX13 SH3 domain but having other typical
      features. It is readily detected with the jackhmmer database search program, but
      not with PSI-BLAST. This is the first time different PEX13 isoforms are reported
      in a single organism. We show that this PEX13.2, like the PEX13.1 previously
      described, is associated with glycosomes and that its depletion by RNA
      interference affects the biogenesis of the organelles and viability of
      trypanosomes. The features considered typical of PEX13s are discussed.

PMID- 22641037
TI  - P4-ATPase ATP8A2 acts in synergy with CDC50A to enhance neurite outgrowth.
AB  - P(4)-ATPases are lipid flippases that transport phospholipids across cellular
      membranes, playing vital roles in cell function. In humans, the disruption of the
      P(4)-ATPase ATP8A2 gene causes a severe neurological phenotype. Here, we found
      that Atp8a2 mRNA was highly expressed in PC12 cells, hippocampal neurons and the
      brain. Overexpression of ATP8A2 increased the length of neurite outgrowth in NGF
      induced PC12 cells and in primary cultures of rat hippocampal neurons. Inducing
      the loss of function of CDC50A in hippocampal neurons via RNA interference
      reduced neurite outgrowth, and the co-overexpression of CDC50A and ATP8A2 in PC12
      cells enhanced NGF-induced neurite outgrowth. These results indicate that ATP8A2,
      acting in synergy with CDC50A, performs an important role in neurite outgrowth in
      neurons.

PMID- 22641038
TI  - Mechanistic details of the DNA recognition by the Dnmt1 DNA methyltransferase.
AB  - A recently solved Dnmt1-DNA crystal structure revealed several enzyme-DNA
      contacts and large structural rearrangements of the DNA at the target site,
      including the flipping of the non-target strand base of the base pair flanking
      the CpG site and formation of a non-canonical base pair between the non-target
      strand Gua and the flanking base pair. Here, we show that the contacts of the
      enzyme to the target base and the Gua:5mC base pair that are observed in the
      structure are very important for catalytic activity. The contacts to the non
      target strand Gua are not important since its exchange by Ade stimulated
      activity. Except target base flipping, we could not find evidence that the DNA
      rearrangements have a functional role.

PMID- 22641040
TI  - Functional analysis of the conserved histidine residue of Bamboo mosaic virus
      capping enzyme in the activity for the formation of the covalent enzyme-m7GMP
      intermediate.
AB  - The alphavirus-like mRNA capping enzyme of Bamboo mosaic virus (BaMV) exhibits an
      AdoMet-dependent guanylyltransferase activity by which the methyl group of AdoMet
      is transferred to GTP, leading to the formation of m(7)GTP, and the m(7)GMP
      moiety is next transferred to the 5' end of ppRNA via a covalent enzyme-m(7)GMP
      intermediate. The function of the conserved H68 of the BaMV capping enzyme in the
      intermediate formation was analyzed by mutagenesis in this study. The nature of
      the bond linking the enzyme and m(7)GMP was changed in the H68C mutant protein,
      strongly suggesting that H68 covalently binds to m(7)GMP in the intermediate.

PMID- 22641041
TI  - Genome-scale metabolic flux analysis of Streptomyces lividans growing on a
      complex medium.
AB  - Constraint-based metabolic modeling comprises various excellent tools to assess
      experimentally observed phenotypic behavior of micro-organisms in terms of
      intracellular metabolic fluxes. In combination with genome-scale metabolic
      networks, micro-organisms can be investigated in much more detail and under more
      complex environmental conditions. Although complex media are ubiquitously applied
      in industrial fermentations and are often a prerequisite for high protein
      secretion yields, such multi-component conditions are seldom investigated using
      genome-scale flux analysis. In this paper, a systematic and integrative approach
      is presented to determine metabolic fluxes in Streptomyces lividans TK24 grown on
      a nutritious and complex medium. Genome-scale flux balance analysis and
      randomized sampling of the solution space are combined to extract maximum
      information from exometabolome profiles. It is shown that biomass maximization
      cannot predict the observed metabolite production pattern as such. Although this
      cellular objective commonly applies to batch fermentation data, both input and
      output constraints are required to reproduce the measured biomass production
      rate. Rich media hence not necessarily lead to maximum biomass growth. To
      eventually identify a unique intracellular flux vector, a hierarchical
      optimization of cellular objectives is adopted. Out of various tested secondary
      objectives, maximization of the ATP yield per flux unit returns the closest
      agreement with the maximum frequency in flux histograms. This unique flux
      estimation is hence considered as a reasonable approximation for the biological
      fluxes. Flux maps for different growth phases show no active oxidative part of
      the pentose phosphate pathway, but NADPH generation in the TCA cycle and NADPH
      transdehydrogenase activity are most important in fulfilling the NADPH balance.
      Amino acids contribute to biomass growth by augmenting the pool of available
      amino acids and by boosting the TCA cycle, particularly when using glutamate and
      aspartate. Depletion of glutamate and aspartate causes a distinct shift in fluxes
      of the central carbon and nitrogen metabolism. In the current work, hurdles
      encountered in flux analysis at a genome-scale level are addressed using
      hierarchical flux balance analysis and uniform sampling of the constrained
      solution space. This general framework can now be adopted in further studies of
      S. lividans, e.g., as a host for heterologous protein production.

PMID- 22641043
TI  - Hepatitis: New doubts about preventing HAV superinfection in chronic HCV.

PMID- 22641039
TI  - Matrix-dependent perturbation of TGFbeta signaling and disease.
AB  - Transforming growth factor beta (TGFbeta) is a multipotent cytokine that is
      sequestered in the extracellular matrix (ECM) through interactions with a number
      of ECM proteins. The ECM serves to concentrate latent TGFbeta at sites of
      intended function, to influence the bioavailability and/or function of TGFbeta
      activators, and perhaps to regulate the intrinsic performance of cell surface
      effectors of TGFbeta signal propagation. The downstream consequences of TGFbeta
      signaling cascades in turn provide feedback modulation of the ECM. This review
      covers recent examples of how genetic mutations in constituents of the ECM or
      TGFbeta signaling cascade result in altered ECM homeostasis, cellular performance
      and ultimately disease, with an emphasis on emerging therapeutic strategies that
      seek to capitalize on this refined mechanistic understanding.

PMID- 22641044
TI  - Cancer: Net closes in on genetics of liver fluke-associated cholangiocarcinoma.

PMID- 22641047
TI  - IBD: Lighting the way for steroid withdrawal in Crohn's disease.

PMID- 22641050
TI  - Current-voltage characteristics of grain boundaries in polycrystalline Sr-doped
      LaGaO3.
AB  - The oxide-ion current across grain boundaries in a polycrystalline LaGaO(3)
      ceramic doped with 1 mol% Sr(2+) increases non-linearly with the applied dc-bias
      to present a transition from ohmic to superohmic where the bias exceeds the
      thermal voltage, verifying that a Schottky-type potential barrier exists at the
      grain boundary in acceptor-doped LaGaO(3) to limit the internal current.

PMID- 22641051
TI  - Anthraquinone with tailored structure for a nonaqueous metal-organic redox flow
      battery.
AB  - A nonaqueous, hybrid metal-organic redox flow battery based on tailored
      anthraquinone structure is demonstrated to have an energy efficiency of ~82% and
      a specific discharge energy density similar to those of aqueous redox flow
      batteries, which is due to the significantly improved solubility of anthraquinone
      in supporting electrolytes.

PMID- 22641049
TI  - Genetics of IL28B and HCV--response to infection and treatment.
AB  - The IL28B locus attracted the attention of HCV researchers after a series of
      genome-wide association studies independently identified a strong association
      between common IL28B polymorphisms and the outcome of PEG-IFN-alpha plus
      ribavirin combination therapy in patients chronically infected with HCV genotype
      1. This association was subsequently replicated for other HCV genotypes and has
      been linked to spontaneous eradication of HCV, development of steatosis and
      biochemical changes (such as altered levels of gamma-glutamyl transpeptidase and
      LDL). Despite the introduction of direct-acting antiviral drugs, IL28B genetics
      are likely to play a part in patient selection and treatment decisions-moving
      towards a personalized approach to therapy. In HCV-infected patients with the so
      called favourable IL28B genotype (rs12979860 CC; associated with better treatment
      response), hepatic expression levels of IL28B and interferon-stimulated genes
      seem to be reduced at baseline, but are induced more strongly after IFN-alpha
      administration, perhaps resulting in more effective elimination of the virus.
      Clarification of the mechanisms underlying these biological phenomena will lead
      to improved understanding of the antiviral effects of IFN-lambda and, ideally, to
      the development of better therapies against HCV infection. This Review summarizes
      current understanding of the role of IL28B in HCV infection and response to
      therapy.

PMID- 22641052
TI  - siRNA knockdown of ADAM-10, but not ADAM-17, significantly reduces fractalkine
      shedding following pro-inflammatory cytokine treatment in a human adult brain
      endothelial cell line.
AB  - Fractalkine shedding is believed to occur constitutively and following induction
      via the activity of two membrane-bound enzymes, ADAM-10 and ADAM-17. However, our
      previous work suggested that ADAM-17 is not involved in the proteolytic release
      of fractalkine under TNF treatment of a human adult brain endothelial cell line,
      hCMEC/D3. The pro-inflammatory cytokine, TNF, has previously been shown to be
      expressed in the perivascular cuffs in multiple sclerosis. Here we sought to
      identify, using siRNAs to silence the expression of ADAM-10 and ADAM-17, whether
      ADAM-10 is responsible for TNF-induced shedding of fractalkine from the cell
      membrane in hCMEC/D3. Our findings suggest that ADAM-10, and not ADAM-17, is the
      major protease involved in fractalkine release under pro-inflammatory conditions
      in this human adult brain endothelial cell model.

PMID- 22641053
TI  - Mechanisms of Bv8-induced biphasic hyperalgesia: increased excitatory transmitter
      release and expression.
AB  - Bv8 is a pronociceptive peptide that binds to two G-protein coupled prokineticin
      receptors, PK-R1 and PK-R2. These receptors are localized in the dorsal horn of
      the spinal cord and dorsal root ganglia (DRG) of nociceptive neurons in rodents.
      Systemic administration of Bv8 elicits a biphasic reduction in nociceptive
      thresholds to thermal and mechanical stimuli. Here, the possibility that Bv8
      might directly modulate the expression and release of excitatory transmitters
      within the early and late phases of hyperalgesia was evaluated. Administration of
      Bv8 to mouse lumbar spinal cord sections produced a direct, significant and
      concentration-related release of CGRP. Bv8- or capsaicin-stimulated CGRP release
      was markedly enhanced in tissues taken from Bv8-pretreated mice during the late,
      but not the early, phase of hyperalgesia. Pretreatment of rats with protein
      synthesis inhibitors blocked the expression of the late, but not early, phase of
      Bv8-induced hyperalgesia. Finally, during the late-phase of hyperalgesia, there
      was an upregulation of CGRP and substance P immunoreactivity in the rat lumbar
      dorsal horn and DRG. Such upregulation was prevented by pretreatment with protein
      synthesis inhibitors. These data suggest that Bv8 induces hyperalgesia by direct
      release of excitatory transmitters in the spinal cord, consistent with the first
      phase of hyperalgesia. Additionally, Bv8 elicits a subsequent, protein-synthesis
      dependent increase in expression and release of excitatory transmitters that may
      underlie the long-lasting second phase of hyperalgesia. Activation of
      prokineticin receptors may therefore contribute to persistent hyperalgesia
      occurring as a consequence of tissue injury further suggesting that these
      receptors are attractive targets for development of therapeutics for pain
      treatment.

PMID- 22641054
TI  - Enhanced expression of nesfatin/nucleobindin-2 in white adipose tissue of
      ventromedial hypothalamus-lesioned rats.
AB  - Nesfatin-1, an anorexigenic protein, is ubiquitously expressed in the body.
      However, the exact mechanism underlying the in vivo regulation of production of
      nesfatin/nucleobindin-2 (NUCB2), a precursor protein of nesfatin-1, is unknown.
      We investigated the influence of modulation of autonomic nerve activity by a
      ventromedial hypothalamus (VMH) lesion and the subsequent effect on
      nesfatin/NUCB2 production in rat tissues innervated by the peripheral nervous
      system. Nesfatin/NUCB2 is strongly expressed in the pancreas and liver,
      moderately expressed in subcutaneous and visceral fat tissues and interscapular
      brown adipose tissue (iBAT), but is weakly expressed in the skeletal muscles. Our
      study results showed that the VMH lesion in VMH-lesioned rats did not affect
      nesfatin/NUCB2 expression in the pancreas, liver, skeletal muscle, and iBAT;
      however, the protein expression was significantly high in both subcutaneous and
      visceral fat tissues. In addition, continuous peripheral administration of
      carbachol for 5 days did not affect nesfatin/NUCB2 expression, but chemical
      sympathectomy using 6-hydroxydopamine mimicked the effect of VMH lesion by
      showing significantly high nesfatin/NUCB2 expression in the subcutaneous fat
      tissues. These results show that VMH lesion can modulate the autonomic nervous
      system activity and balance and increase nesfatin/NUCB2 expression in white
      adipose tissues of rats. Further, this action may be mediated via inhibition of
      the sympathetic nerve activity.

PMID- 22641055
TI  - Cysteine decrease following acute Levodopa intake in patients with Parkinson's
      disease.
AB  - The thiol homeostasis determines the redox milieu and thus scavenging of free
      radicals by antioxidants like glutathione (GSH). GSH is formed out of cysteine in
      combination with l-glycine and glutamine acid. An up regulation of free radical
      occurrence is looked upon as one key feature of chronic neurodegeneration.
      Levodopa (LD) is under suspicion to support synthesis of free radicals via the
      degradation of its derivative dopamine in abundant mitochondria. Objectives were
      to investigate the impact of LD on free cysteine turnover in plasma. 200mg
      LD/50mg carbidopa (CD) were administered to 13 patients with Parkinson's disease
      under standardised conditions. Plasma levels of LD and free cysteine were
      measured before, 60- and 80-min after the LD/CD application. Cysteine
      concentrations decayed, expectedly LD levels increased. Cysteine decrease may
      result from an up regulation of GSH synthesis to encounter augmented appearance
      of free radicals associated with LD turnover via mitochondrial monoaminooxidase.

PMID- 22641056
TI  - Molecular subtypes of breast carcinoma in Egyptian women: clinicopathological
      features.
AB  - Breast carcinoma may be classified into distinct molecular subtypes based on
      immunohistochemical markers for estrogen, progesterone and Her-2/neu receptors.
      The aim of the study was to identify the clinicopathological features of the
      molecular subtypes of breast carcinoma in our locality. A total of 274 surgically
      resected breast carcinomas were selected from the files of the Dr. KRZ referral
      pathology laboratory, Mansoura, Egypt, and the Pathology Department of Mansoura
      University. Molecular subtypes were classified into luminal A, luminal B, Her
      2/neu-expressing and triple-negative. Clinicopathological and histological
      features of molecular subtypes were analyzed. Luminal A subtype was the most
      prevalent (41.2%), followed by triple-negative subtype (28.5%), then Her2
      expressing subtype (19.4%) and luminal B subtype (13.9%). The commonest
      histological type was infiltrating duct carcinoma (83.2%), followed by
      infiltrating lobular carcinoma (9.1%) and medullary carcinoma (3.2%). The luminal
      A subtype was significantly correlated to low tumor grade, lower number of
      positive lymph nodes metastasis, absence of both necrosis and syncytial growth
      pattern. We concluded that the commonest molecular subtype of invasive breast
      carcinoma among Egyptian women is luminal subtype A, which displayed favorable
      features. Triple-negative subtype and medullary carcinomas are present in a ratio
      higher than in western countries.

PMID- 22641058
TI  - A comparative study of magnetic and dielectric behaviors for La(1-x)Bi(x)Mn(1
      y)Fe(y)O3 series (with x = 0.5, 0.7 and y = 0.3, 0.7).
AB  - We have carried out an extensive investigation into the effect of doping on both
      the A- and B-sites for the multiferroic La(0.5)Bi(0.5)Mn(0.5)Fe(0.5)O(3) in
      relation to its physical properties. The temperature dependent magnetization and
      dielectric response are determined for different percentages of Bi- and Fe
      substitutions. For La(0.5)Bi(0.5)Mn(0.7)Fe(0.3)O(3), there is a prominent
      ferromagnetic transition T(C) around 110 K, whereas the other
      La(0.5)Bi(0.5)Mn(0.3)Fe(0.7)O(3) and La(0.3)Bi(0.7)Mn(0.3)Fe(0.7)O(3) phases fail
      to exhibit any clear transition. On the other hand, for the Fe-rich phases, the
      coercive field increases to 2450 Oe compared to 1720 Oe (for the Mn-rich phase).
      All the compositions exhibit coexistence of ferromagnetic and antiferromagnetic
      phases at low temperatures. The temperature dependent dielectric constant of the
      investigated samples varies from 32,000 to 500 at room temperature and the data
      has been analyzed using the universal dielectric response model.

PMID- 22641057
TI  - Integrated refolding techniques for Schistosoma japonicum MTH1 overexpressed as
      inclusion bodies in Escherichia coli.
AB  - The full-length cDNA of MTH1in Schistosoma japonicum was previously isolated.
      However, insoluble protein expression in Escherichia coli is the biggest
      bottleneck limiting biological and biophysical studies. Protein aggregation could
      not be significantly prevented using solubilization or refolding techniques, and
      denatured MTH1 protein could not be refolded to the native monomer form. Hence,
      integrating several refolding techniques within the protein refolding process of
      MTH1, a large amount of active MTH1 was obtained for protein crystallization. We
      primarily utilized the two-step-denaturing and refolding method and the protein
      refolding screening technique, as well as the continuous dialysis method. First,
      we identified the refolding buffer composition that allowed for successful
      refolding to overcome protein precipitation. Next, we used the two-step
      denaturing and refolding method and the continuous dialysis method to suppress
      protein aggregation. In the end, we obtained 15 mg of active MTH1 monomer with
      95% purity from 0.5l medium. Integrated refolding techniques proved to be
      excellent for obtaining the native monomer of S. japonicum MTH1 from inclusion
      bodies, paving the way for future biological and biophysical studies.

PMID- 22641059
TI  - 'Don't cross a man's feet': Hmong parent-daughter communication about sexual
      health.
AB  - Parent-adolescent communication about sexual health is one strategy to encourage
      healthy adolescent sexual behaviour. However, this literature has largely
      overlooked immigrant families. Hmong youth, identified as facing extreme
      challenges to parent-adolescent communication, are considered. Content analysis
      was used to examine parent-adolescent communication about sexual health for forty
      four pregnant or parenting Hmong adolescent girls. The minority of adolescents
      recalled an actual conversation about sexual health in their families with
      mothers most often identified as the source. Their stories reflect discussions
      about abstinence, puberty, pregnancy, and STIs - with much information being
      inaccurate. With culture being a recurrent theme, communication was reported to
      be hindered by cultural traditions, comfort level, applicability, and perceived
      consequences. The results identify opportunities for culturally-relevant sex
      education materials in the Hmong community.

PMID- 22641060
TI  - Proliferating type pilomatricoma presenting with alopecia.

PMID- 22641061
TI  - Non-linear pharmacokinetics of octaarginine-modified lipid nanoparticles:
      barriers from in vitro to in vivo.
AB  - A rational development of an efficient siRNA delivery system is important for
      streamlining the RNAi-based drug development process. However, a huge gap
      frequently exists between in vitro and in vivo activity, which is the rate
      limiting step for developing versatile nanoparticles. We report herein on a
      remarkable non-linearity in pharmacokinetics (PK), but not pharmacodynamics (PD)
      using octaarginine (R8) modified lipid nanoparticles in mice. A quantitative
      study of siRNA molecules between cultured cells and mouse liver revealed a high
      correlation between intracellular siRNA molecules and their RNAi activities,
      indicating that there was no significant difference in the efficiency in PD. In
      contrast, a remarkable difference was observed in the non-linearity in PK.
      Quantitative analysis of the time profile for siRNA showed that the percentage of
      siRNA accumulation in mice was severely decreased with decreasing input dose
      compared to in vitro data. These unexpected data reveal an important clue to
      bridging the gap between in vitro and in vivo activity.

PMID- 22641062
TI  - PLGA nanoparticles and nanosuspensions with amphotericin B: Potent in vitro and
      in vivo alternatives to Fungizone and AmBisome.
AB  - This paper describes the development of poly(D,L-lactide-co-glycolide) (PLGA)
      nanoparticles (NPs) and nanosuspensions with the polyene antibiotic amphotericin
      B (AmB). The nanoformulations were prepared using nanoprecipitation and were
      characterised with respect to size, zeta potential, morphology, drug
      crystallinity and content. Standard in vitro sensitivity tests were performed on
      MRC-5 cells, red blood cells, Leishmania infantum promastigotes and intracellular
      amastigotes and the fungal species Candida albicans, Aspergillus fumigatus and
      Trichophyton rubrum. The in vivo efficacy was assessed and compared to that of
      Fungizone and AmBisome in the acute A. fumigatus mouse model at a dose of 2.5 and
      5.0mg/kg AmB equivalents. The developed AmB nanoformulations were equivalently or
      more effective against the different Leishmania stages and axenic fungi in
      comparison with the free drug. The in vitro biological activity, and especially
      hemolytic activity, clearly depended on the preparation parameters of the
      different nanoformulations. Further, we demonstrated that the superior in vitro
      antifungal activity could be extrapolated to the in vivo situation. At equivalent
      dose, the optimal AmB-loaded PLGA NP was about two times and the AmB
      nanosuspension about four times more efficacious in reducing the total burden
      than AmBisome. The developed AmB nanomedicines could represent potent and cost
      effective alternatives to Fungizone and AmBisome.

PMID- 22641063
TI  - Deep subcutaneous adipose tissue is more saturated than superficial subcutaneous
      adipose tissue.
AB  - Upper body abdominal subcutaneous adipose tissue (SAT) can be divided into deep
      SAT (DSAT) and superficial SAT (SSAT) depots. Studies on adipose tissue fatty
      acid (FA) composition have made no distinction between these two depots. The aim
      of this study is to determine whether DSAT and SSAT differ in FA composition. We
      studied the FA composition of DSAT and SSAT in 17 male and 13 female volunteers
      using non-invasive proton magnetic resonance spectroscopy in vivo. Magnetic
      resonance imaging was used to differentiate between DSAT and SSAT. Adipose tissue
      spectra were analysed for lipid unsaturation, or double bond (DB) content, and
      polyunsaturation (PU), according to previously validated methods. The DSAT depot
      was more saturated than the SSAT depot, in both men (0.833 +/- 0.012 vs 0.846 +/-
      0.009 DB, P<0.002) and women (0.826 +/- 0.018 vs 0.850 +/- 0.018 DB, P<0.002). In
      contrast, PU did not differ between DSAT and SSAT in either men (0.449 +/- 0.043
      vs 0.461 +/- 0.044 PU, P=0.125) or women (0.411 +/- 0.070 vs 0.442 +/- 0.062 PU,
      P=0.234) and displayed a close correlation between the depots (R=0.908, P<0.001,
      n=30). The higher saturation in DSAT compared with SSAT can be attributed to a
      higher ratio of saturated to monounsaturated FAs. These results should be taken
      into account when determining the FA composition of SAT.

PMID- 22641064
TI  - Formoterol, a highly beta2-selective agonist, increases energy expenditure and
      fat utilisation in men.
AB  - BACKGROUND: The sympathetic nervous system regulates energy metabolism via beta
      adrenoreceptors. Therapeutic exploitation of previous beta2-adrenegic agonists
      for metabolic benefits has been hindered by cross stimulation of cardiac beta1
      adrenoceptor, causing tachycardia. Formoterol is a novel highly beta2-selective
      adrenergic agonist and holds promise as a beta2-agonist that could impart
      selective beneficial metabolic effects. OBJECTIVE: To investigate the metabolic
      effects of formoterol on energy and substrate metabolism. PARTICIPANTS: Healthy
      volunteers. DESIGN: (1) Dose-finding study, step-wise incremental design of
      weekly administration of 80, 160 and 320 MUg daily of formoterol in four subjects
      and, (2) metabolic study, an open-label metabolic evaluation of 1-week treatment
      in eight men using a dose determined from (1). MAIN OUTCOME: Resting energy
      expenditure (EE), diet-induced thermogenesis (DIT) and fat oxidation (Fox) using
      indirect calorimetry, heart rate and plasma non-esterified fatty acid (NEFA)
      levels. RESULTS: In the dose-finding study, all three doses increased resting EE
      and Fox with the 320 MUg dose significantly increasing heart rate. In the
      metabolic study, the selected 160 MUg daily dose increased resting EE by 13 +/-
      2% (P<0.001) and Fox by 23 +/- 4% (P<0.01), but not DIT. Plasma NEFA levels rose
      by 16 +/- 2% (P<0.01). Heart rate did not change significantly. Out of the eight
      subjects, six reported tremor and palpitation, two lost appetite and one suffered
      from insomnia. CONCLUSIONS: At a dose of 160 MUg per day, formoterol increases
      resting EE and fat utilization without inducing tachycardia. From this first
      metabolic evaluation in humans, we conclude that formoterol imparts beneficial
      metabolic changes that may be exploited for therapy of obesity.

PMID- 22641065
TI  - Cocoa polyphenols suppress adipogenesis in vitro and obesity in vivo by targeting
      insulin receptor.
AB  - OBJECTIVE: To investigate the inhibitory effect of cocoa polyphenol extract (CPE)
      on adipogenesis and obesity along with its mechanism of action. METHODS AND
      RESULTS: 3T3-L1 preadipocytes were cultured with isobutylmethylxanthine,
      dexamethasone and insulin (MDI), and male C57BL/6N mice (N=44) were fed a high
      fat diet (HFD) for 5 weeks with or without CPE. CPE at 100 or 200 MUg ml(-1)
      inhibited MDI-induced lipid accumulation without diminishing cell viability. In
      particular, CPE reduced the protein expression levels of PPARgamma and CEBPalpha,
      and blocked mitotic clonal expansion (MCE) of preadipocytes by reducing
      proliferating signaling pathways. This in turn attenuates lipid accumulation
      during the differentiation of 3T3-L1 preadipocytes. CPE effectively suppressed
      MDI-induced phosphorylation of extracellular signal-regulated kinase (ERK) and
      Akt, and their downstream signals. We then examined whether CPE regulates insulin
      receptor (IR), a common upstream regulator of ERK and Akt. We found that although
      CPE does not affect the protein expression level of IR, it significantly inhibits
      the activity of IR kinase via direct binding. Collectively, the results suggested
      that CPE, a direct inhibitor of IR kinase activity, inhibits cellular
      differentiation and lipid accumulation in 3T3-L1 preadipocytes. Consistently, CPE
      attenuated HFD-induced body weight gain and fat accumulation in obese mice fed
      with a HFD. We also found that HFD-induced increased fasting glucose levels
      remained unaffected by CPE. CONCLUSION: This study demonstrates that CPE inhibits
      IR kinase activity and its proliferative downstream signaling markers, such as
      ERK and Akt, in 3T3-L1 preadipocytes, and also prevents the development of
      obesity in mice fed with a HFD.

PMID- 22641066
TI  - Adaptation of human adipose tissue to hypocaloric diet.
AB  - Hypocaloric diet is a key component of the weight-reducing treatment of obesity
      and obesity-related disorders. Hypocaloric diets and the associated weight
      reduction promote improvement of metabolic profile of obese individuals. Among
      the mechanisms that underlie this beneficial metabolic outcome, the diet-induced
      modifications of morphological and functional characteristics of human adipose
      tissue (AT) are believed to have an important role. Prospective studies of
      hypocaloric weight-reducing dietary intervention demonstrate effects on adipocyte
      metabolism, namely lipolysis and lipogenesis, and associated changes of the
      adipocyte size. The endocrine function of AT, which involves cytokine and
      adipokine production by adipocytes, as well as by cells of stromavascular
      fraction, is also regulated by dietary intervention. Related inflammatory status
      of AT is modulated also as a consequence of the changes in recruitment of immune
      cells, mainly macrophages, in AT. Here, we give an overview of metabolic and
      endocrine modifications in human AT induced by a variety of hypocaloric diets.

PMID- 22641067
TI  - A self-assembled DNA nanostructure-amplified quartz crystal microbalance with
      dissipation biosensing platform for nucleic acids.
AB  - A self-assembled DNA nanostructure as an efficient signal amplifier was
      introduced to create a simple and label-free quartz crystal microbalance with
      dissipation monitoring (QCM-D) biosensing platform for highly sensitive and
      selective detection of nucleic acids.

PMID- 22641069
TI  - Introduction. Neurologic sequelae of cancer in children.

PMID- 22641068
TI  - Histone deacetylases activate hepatocyte growth factor signaling by repressing
      microRNA-449 in hepatocellular carcinoma cells.
AB  - BACKGROUND & AIMS: Histone deacetylation regulates chromatin remodeling and
      transcriptional down-regulation of specific genomic regions; it is altered in
      many types of cancer cells. We searched for microRNAs (miRs) that are affected by
      histone deacetylation and investigated the effects in hepatocellular carcinoma
      (HCC) cells. METHODS: HCC cell lines (HepG2, HLE, HLF, and Huh7) and immortalized
      liver cell lines (THLE-2 and THLE-3) were incubated with the histone deacetylase
      inhibitor trichostatin A. Differentially expressed messenger RNAs (mRNAs) and
      miRs were identified by expression profiling. Small interfering RNAs were used to
      reduce levels of histone deacetylases (HDAC)1-3, and HCC cell lines were
      transfected with miR-449. We evaluated growth of xenograft tumors from modified
      cells in nude mice. Cells were analyzed by immunoblot and luciferase reporter
      assays. We analyzed HCC samples from 23 patients. RESULTS: HDAC1-3 were up
      regulated in HCC samples from patients. In cell lines, inhibition of HDAC
      significantly increased levels of hsa-miR-449a. c-MET mRNA, which encodes the
      receptor tyrosine kinase for hepatocyte growth factor, is a target of miR-449.
      Incubation of HCC cells with trichostatin A or transfection with miR-449 reduced
      expression of c-MET and phosphorylation of extracellular signal-regulated kinases
      1 and 2 (downstream effectors of c-MET), increased apoptosis, and reduced
      proliferation. Huh-7 cells transfected with miR-449 formed tumors more slowly in
      mice than cells expressing control miRs. HCC samples from patients had lower
      levels of miR-449 and higher levels of c-MET than human reference. CONCLUSIONS:
      In HCC cells, up-regulation of HDAC1-3 reduces expression of miR-449. miR-449
      binds c-MET mRNA to reduce its levels, promoting apoptosis and reducing
      proliferation of liver cells. Expression of miR-449 slows growth of HCC xenograft
      tumors in mice; this miR might function as a tumor suppressor.

PMID- 22641070
TI  - Pediatric brain tumors and epilepsy.
AB  - Seizures are a common complication of pediatric brain tumors and their treatment.
      This article reviews the epidemiology, evaluation, and treatment of seizures in
      children with brain tumors. Seizures in known brain tumor patients may signify
      tumor progression or recurrence, or treatment-related brain damage, as well as
      other causes, including low drug levels and metabolic disturbances. Careful
      selection of antiepileptic medications is needed in this population. There are
      advantages to nonenzyme-inducing antiepileptic drugs including valproic acid,
      which has potential antitumoral properties as a histone deacetylase inhibitor.
      Tumor surgery cures many cases of pediatric tumor-associated seizures, and some
      children are controlled with anti-epileptic medication, however additional
      epilepsy surgery may be needed for refractory cases.

PMID- 22641071
TI  - Chemotherapy-induced peripheral neuropathy in pediatric cancer patients.
AB  - Chemotherapy forms the backbone of treatment for many types of pediatric cancers,
      but a main side effect of treatment is chemotherapy-induced peripheral neuropathy
      (CIPN). Damage to the peripheral nervous system by chemotherapeutic agents can
      occur at the axon, cell body, or myelin level, and the mechanism of damage
      differs based on the specific chemotherapeutic agent used. This review provides
      background on the current knowledge of pathophysiology, assessment, and
      intervention for CIPN, focusing specifically on issues relevant in pediatric
      cancers patients. Although specific, standardized measures of CIPN are available
      for adults, such measures are limited for use in the pediatric populations.
      Likewise, clinical trials for prevention and treatment of this neuropathy and
      related symptoms are rare in pediatrics, but some information can be gained from
      the basic and adult literature.

PMID- 22641072
TI  - Stroke and cerebrovascular complications in childhood cancer survivors.
AB  - The outcomes for childhood cancer have drastically improved over the last several
      decades. Previously, irradiation was commonly used for blood-borne (leukemia,
      lymphoma) cancers and neck and brain tumors. Radiation therapy remains the
      mainstay of treatment for highly malignant cancers of head and neck and for some
      primary central nervous system tumors. Unfortunately, radiation therapy has been
      implicated as a contributor to many late effects of treatment, including
      cerebrovascular disease from large-vessel vascular injury, stroke, moyamoya,
      mineralizing microangiopathy, to stroke-like migraine. This review summarizes the
      pathophysiology of these disorders in relationship to treatment with and without
      radiation as well as the relevant manifestations of radiation-induced
      cerebrovascular disease. Patient populations at highest risk and current
      recommendations for health providers and patient education are emphasized when
      possible.

PMID- 22641073
TI  - Sleep disorders in children with cancer.
AB  - Approximately three-fourths of all pediatric cancer patients will be long-term
      survivors; however, there can be a steep cost for cancer survivorship. Cancer
      treatment involves exposure to chemotherapy, surgical intervention, and
      radiation, which can cause lasting long-term toxicities. Children with brain
      tumors have the highest prevalence of long-term morbidities. These effects can be
      attributed to direct neurologic damage to the developing brain caused by tumor,
      hydrocephalus, surgical removal of the tumor, and the effects of irradiation. The
      late effects experienced by childhood cancer survivors involve multiple domains,
      one of which is sleep disorders. Sleep dysfunction has an increased prevalence in
      the pediatric cancer survivor population. These issues are disruptive to patients
      and cause a decrease in quality of life. This review focuses on sleep disorders
      that occur in pediatric cancer survivors and discusses the possible causes, the
      assessments used to determine specific sleep disorders, and treatment modalities
      used to ameliorate this dysfunction with the hope of improving patient's quality
      of life.

PMID- 22641074
TI  - Neurocognitive dysfunction in survivors of childhood brain tumors.
AB  - Newer treatments have resulted in increasing numbers of survivors of childhood
      cancer, for whom neurological and neurocognitive toxicity directly impacts
      overall functioning and quality of life. There are multiple disease- and host
      related factors that influence the development of cancer-related neurocognitive
      dysfunction, which can progress over time and lead to significant functional
      impairments. This article provides an overview of the types of neurocognitive
      deficits seen in survivors of childhood brain tumors, the tools used to assess
      neurocognitive function, and the factors that impact its severity. This provides
      a framework for consideration of potential areas for primary prevention by
      reducing treatment-related toxicity as well as interventions, using behavioral
      and pharmacologic treatments.

PMID- 22641075
TI  - A review of secondary central nervous system tumors after treatment of a primary
      pediatric malignancy.
AB  - Despite remarkable strides in the treatment of pediatric malignancies over the
      last 50 years, long-lasting sequelae and secondary malignancies continue to
      plague this population. This article reviews the incidence, diagnosis, and
      etiology of secondary central nervous system tumors in the setting of a history
      of primary pediatric malignancy. Particular attention is paid to central nervous
      system tumors presenting after treatment of leukemia and primary brain tumors, as
      well as the role of treatment and underlying cancer predisposition syndromes in
      the risk of developing these secondary tumors.

PMID- 22641076
TI  - Primary pancreatic leiomyosarcoma: a retrospective analysis of clinical
      characteristics and prognosis of this rare disease.
AB  - BACKGROUND/AIMS: Primary pancreatic leiomyoarcoma (PLMS) is a rare disease; its
      clinical characters and prognosis are poorly demonstrated. This study aimed to
      investigate the tumor's clinical characters and to reveal the true outcome.
      METHODOLOGY: A retrospective review of both Chinese and worldwide PLMS patients
      were performed. Data was collected and analyzed and overall survival was
      described by Kaplan-Meier curve. RESULTS: In total, there were 9 cases identified
      in China and 55 cases identified in the worldwide literature. Incidence rate was
      general equal in gender and had an increased trend with age(mean +SD: 55+14
      years). Abdominal pain, mass and weight loss were the most common presentations,
      mean tumor size was 10cm (SD 7.2cm) and most of them presented as a solid mass.
      Forty six cases accepted operation, 33 of which obtained a radical resection.
      Median overall survival time was 27 months.The patients who accepted radical
      resection had an obviously improved prognosis over non-resectable patients.
      CONCLUSIONS: PLMS commonly occurred in the mid-age people and there was lack of
      specific non-invasive methods for precise preoperative diagnosis.PLMS has a much
      better prognosis compared with pancreatic ductal adenocarcinoma. Radical
      resection is the only hope for improving the outcome of this malignancy.

PMID- 22641077
TI  - Ex vivo-expanded bone marrow mesenchymal stem cells facilitate recovery from
      chemically induced acute liver damage.
AB  - BACKGROUND/AIMS: To investigate the feasibility and mechanism of liver damage
      repair using BMSCs, we investigated the potential for BMSCs in recovery from
      liver damage, using the CCl4-induced rat model for liver damage. METHODOLOGY:
      Phenotypings of BMSCs of the third generation were analyzed by flow cytometry.
      BMSCs labelled by BrdU were infused via the tail vein of CCl4-induced rat model.
      The labeling yields ob-served were detected by flow cytometry and liver samples
      were taken for immunohistochemistry. Concentration changes of AST, ALT and AKP
      were observed by a serum enzymology test after transplantation. RESULTS: The
      BrdU' cells in recipient livers were detect-ed on day 7 after BMSCs
      transplantation and engraft-ed cells were found in the peri-portal regions of the
      hepatic lobule and on day 14 more of them spread throughout the lobules. BMSCs
      engraftments were detected on whole hepatic parenchyma. The serum lev-els of ALT,
      AST and AKP in group 3 were all lower than those of group 2 from the 7h to 28th
      day. CONCLUSIONS: Ex vivo-expanded BMSCs were capable of relocating to the
      chemically-injured liver. Transplantation of these pluripotent stem cells
      appeared to improve serum indices of liver function.

PMID- 22641078
TI  - Chronic kidney disease: Albuminuria or CKD stage as best marker of CVD in
      diabetes?

PMID- 22641079
TI  - Alport syndrome: About time--treating children with Alport syndrome.

PMID- 22641080
TI  - Chronic kidney disease: The CKD-EPI equation--accurately stratifying risk in CKD.

PMID- 22641081
TI  - Chronic kidney disease: Estimating GFR--the right equation for the right
      population.

PMID- 22641082
TI  - Cardiovascular disease: Stenting in renovascular disease--good news for the
      heart?

PMID- 22641083
TI  - Accumulation of SNAP25 in mouse gustatory and somatosensory cortices in response
      to food and chemical stimulation.
AB  - Food intake stimuli, including taste, somatosensory, and tactile stimuli, are
      received by receptors in the oral cavity, and this information is then
      transferred to the cerebral cortex. Signals from recently ingested food during
      the weaning period can affect synaptic transmission, resulting in biochemical
      changes in the cerebral cortex that modify gustatory and somatosensory nervous
      system plasticity. In this study, we investigated the expression patterns of
      molecular markers in mouse gustatory and somatosensory cortices during the
      weaning period. The expression of synaptosomal-associated protein 25 (SNAP25), a
      component of the soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor (SNARE) complex, was increased in the insular and somatosensory cortices
      at postnatal week 3 compared to postnatal week 2. Additionally, SNAP25 protein in
      the cerebral cortex accumulated in weaning mice fed solid food but not in mice
      fed only mother's milk at the weaning stage. Chemical stimulation by saccharin or
      capsaicin at the weaning stage also increased SNAP25 immunoreactivity in the
      insular or somatosensory cortical area, respectively. These results suggest that
      recently ingested chemical signals in the oral cavity during weaning increase the
      accumulation of SNAP25 in the gustatory and somatosensory cortices and promote
      neural plasticity during the development of the gustatory and somatosensory
      nervous systems.

PMID- 22641084
TI  - H(2)S functions as a nociceptive messenger through transient receptor potential
      ankyrin 1 (TRPA1) activation.
AB  - Hydrogen sulfide (H(2)S), an endogenous gasotransmitter, modulates various
      biological functions, including nociception. It is known that H(2)S causes
      neurogenic inflammation and elicits hyperalgesia. Here we show that H(2)S
      activates mouse transient receptor potential ankyrin 1 (TRPA1) channels and
      elicits acute pain, using TRPA1-gene deficient mice (TRPA1(-/-)) and heterologous
      expression system. In wild-type mouse sensory neurons, H(2)S increased the
      intracellular Ca(2+) concentration ([Ca(2+)](i)), which was inhibited by
      ruthenium red (a nonselective TRP channel blocker) and HC-030031 (a TRPA1
      blocker). H(2)S-responsive neurons highly corresponded to TRPA1 agonist-sensitive
      ones. [Ca(2+)](i) responses to H(2)S were observed in neurons from transient
      receptor potential vanilloid 1 (TRPV1(-/-)) mice but not from TRPA1(-/-) mice.
      Heterologously expressed mouse TRPA1, but not mouse TRPV1, was activated by
      H(2)S. H(2)S-induced [Ca(2+)](i) responses were inhibited by dithiothreitol, a
      reducing agent. Analyses of the TRPA1 mutant channel revealed that two cysteine
      residues located in the N-terminal internal domain were responsible for the
      activation by H(2)S. Intraplantar injection of H(2)S into the mouse hind paw
      caused acute pain which was significantly less in TRPA1(-/-) mice. The
      [Ca(2+)](i) responses to H(2)S in sensory neurons and in heterologously expressed
      channels, and pain-related behavior induced by H(2)S were enhanced under acidic
      conditions. These results suggest that H(2)S functions as a nociceptive messenger
      through the activation of TRPA1 channels. TRPA1 may be a therapeutic target for
      H(2)S-related algesic action, especially under inflammatory conditions.

PMID- 22641085
TI  - Overexpression of the vesicular acetylcholine transporter increased acetylcholine
      release in the hippocampus.
AB  - Cholinergic neurotransmission in the hippocampus is involved in cognitive
      functions, including learning and memory. Strategies to enhance septohippocampal
      cholinergic neurotransmission may therefore be of therapeutic value to limit
      cognitive decline during cholinergic dysfunction. In addition to current
      strategies being developed, such as the use of acetylcholinesterase inhibitors,
      enhancing acetylcholine (ACh) release may be critical for optimal cholinergic
      neurotransmission. Vesicular acetylcholine transporter (VAChT) activity limits
      the rate of formation of the readily releasable ACh pool. As such, we sought to
      determine the influence of increased VAChT expression on the septohippocampal
      cholinergic system. To do this, we used the B6.eGFPChAT congenic mouse, which we
      show contains multiple gene copies of VAChT. In this transgenic mouse, the
      increased VAChT gene copy number led to an increase in VAChT gene expression in
      the septum and a corresponding enhancement of VAChT protein in the hippocampal
      formation. VAChT overexpression enhanced the release of ACh from ex vivo
      hippocampal slices. From these findings, we conclude that VAChT overexpression is
      sufficient to enhance ACh release in the hippocampal formation. It remains to be
      established whether, in cases of cholinergic deficits, increasing VAChT
      expression would re-establish adequate levels of cholinergic neurotransmission,
      thereby providing a valid therapeutic target.

PMID- 22641086
TI  - Mechanism of the sex difference in neuronal ischemic cell death.
AB  - BACKGROUND: Stroke risk and outcome are different in men and women. We
      hypothesized that this is partly due to an inherent difference in susceptibility
      to ischemia between neurons from male vs. female brains. We tested whether
      neurons from male rodents are more susceptible to in-vitro ischemia than cells
      from females, and if this is related to increased expression of soluble epoxide
      hydrolase (sEH). sEH contributes to neuronal cell death by inactivating
      neuroprotective epoxyeicosatrienoic acids (EETs). METHODS: Rodent cortical
      neurons were cultured, and exposed to oxygen-glucose deprivation (OGD); then cell
      death was measured. EETs levels were determined by LC-MS/MS. Expression of sEH
      encoding ephx2 was determined by qRT-PCR. Western blotting, immunocytochemistry,
      and hydrolase activity assay assessed protein expression and activity. RESULTS:
      Cell death after OGD was higher in neurons from males vs. females, which
      correlated with higher ephx2 mRNA and stronger sEH immunoreactivity. However,
      EETs levels were similar in both sexes and pharmacological inhibition of the
      hydrolase domain of sEH did not abolish the sex difference in cell death. Genetic
      knockout of sEH in mice abolished the sex difference observed in neurons isolated
      from these mice after OGD. CONCLUSIONS: Cultured cortical neurons from females
      are more resistant to ischemia than neurons from males. Neurons from females have
      less sEH activity compared to neurons from males at baseline, although sEH levels
      were not measured after OGD. While pharmacological inhibition of the hydrolase
      domain of sEH does not affect cell death, knockout of the gene encoding sEH
      eradicates the sex difference seen in wild-type neurons, suggesting a role for
      further study of the lesser-known phosphatase domain of sEH and its role in
      sexual dimorphism in neuronal sensitivity to ischemia.

PMID- 22641087
TI  - Fos-activation of FoxP2 and Lmx1b neurons in the parabrachial nucleus evoked by
      hypotension and hypertension in conscious rats.
AB  - The parabrachial nucleus (PB) is a brainstem cell group that receives a strong
      input from the nucleus tractus solitarius regarding the physiological status of
      the internal organs and sends efferent projections throughout the forebrain.
      Since the neuroanatomical organization of the PB remains unclear, our first step
      was to use specific antibodies against two neural lineage transcription factors:
      Forkhead box protein2 (FoxP2) and LIM homeodomain transcription factor 1 beta
      (Lmx1b) to define the PB in adult rats. This allowed us to construct a
      cytoarchitectonic PB map based on the distribution of neurons that constitutively
      express these two transcription factors. Second, the in situ hybridization method
      combined with immunohistochemistry demonstrated that mRNA for glutamate vesicular
      transporter Vglut2 (Slc17a6) was present in most of the Lmx1b+ and FoxP2+
      parabrachial neurons, indicating these neurons use glutamate as a transmitter.
      Third, conscious rats were maintained in a hypotensive or hypertensive state for
      2h, and then, their brainstems were prepared by the standard c-Fos method which
      is a measure of neuronal activity. Both hypotension and hypertension resulted in
      c-Fos activation of Lmx1b+ neurons in the external lateral-outer subdivision of
      the PB (PBel-outer). Hypotension, but not hypertension, caused c-Fos activity in
      the FoxP2+ neurons of the central lateral PB (PBcl) subnucleus. The Kolliker-Fuse
      nucleus as well as the lateral crescent PB and rostral-most part of the PBcl
      contain neurons that co-express FoxP2+ and Lmx1b+, but none of these were
      activated after blood pressure changes. Salt-sensitive FoxP2 neurons in the pre
      locus coeruleus and PBel-inner were not c-Fos activated following blood pressure
      changes. In summary, the present study shows that the PBel-outer and PBcl
      subnuclei originate from two different neural progenitors, contain glutamatergic
      neurons, and are affected by blood pressure changes, with the PBel-outer reacting
      to both hypo- and hypertension, and the PBcl signaling only hypotensive changes.

PMID- 22641088
TI  - Ghrelin-deficient mice have fewer orexin cells and reduced cFOS expression in the
      mesolimbic dopamine pathway under a restricted feeding paradigm.
AB  - Ghrelin is an orexigenic stomach peptide previously found to be important for the
      full display of anticipatory locomotor activity and hypothalamic neuronal
      activation that precedes a daily scheduled meal in mice. Ghrelin is also
      important for food-related motivation and seems to have direct effects in the
      mesocorticolimbic dopamine reward system. Here we hypothesized that neuronal
      activation in reward-related areas in anticipation of a scheduled meal could be
      mediated by elevated ghrelin induced by scheduled feeding, and therefore this
      would be attenuated in ghrelin receptor knock-out (GHSR KO) animals. We found
      that this was indeed the case for the ventral tegmental area and the shell, but
      not the core, of the nucleus accumbens. In addition, our results show a reduction
      in the proportion of activated orexin-immunoreactive (IR) neurons in GHSR KO
      animals in anticipation of the scheduled meal in comparison to the proportion of
      activated orexin neurons in wild type (WT) mice. Interestingly we observed that
      both GHSR and ghrelin KO mice had fewer orexin-IR cells than their WT littermates
      suggesting that lack of ghrelin or sensitivity to ghrelin may play a role in the
      development of the orexin system. Our data also suggest that ghrelin may mediate
      food anticipation, in part, by stimulating both the orexin system and the
      mesolimbic reward system.

PMID- 22641089
TI  - Development and validation of a stability-indicating HPLC assay method for
      simultaneous determination of spironolactone and furosemide in tablet
      formulation.
AB  - The objective of the current study was to develop and validate a simple, precise
      and accurate isocratic stability-indicating reversed-phase high-performance
      liquid chromatography (RP-HPLC) assay method for the determination of
      spironolactone and furosemide in solid pharmaceutical dosage forms. Isocratic RP
      HPLC separation was achieved on an SGE 150 * 4.6 mm SS Wakosil II 5C8RS 5-MUm
      column using a mobile phase of acetonitrile-ammonium acetate buffer (50:50, v/v)
      at a flow rate of 1.0 mL/min. The detection was carried out at 254 nm using a
      photodiode array detector. The drug was subject to oxidation, hydrolysis,
      photolysis and heat to apply stress conditions. The method was validated for
      specificity, linearity, precision, accuracy, robustness and solution stability.
      The method was found to be linear in the drug concentration range of 40-160 ug/mL
      with correlation coefficients of 0.9977 and 0.9953 for spironolactone and
      furosemide, respectively. The precision (relative standard deviation; RSD) among
      a six-sample preparation was 0.87% and 1.1% for spironolactone and furosemide,
      respectively. Repeatability and intermediate precision (RSD) among a six-sample
      preparation were 0.46% and 0.20% for spironolactone and furosemide, respectively.
      The accuracy (recovery) was between 98.05 and 100.17% and 99.07 and 100.58% for
      spironolactone and furosemide, respectively. Degradation products produced as a
      result of stress studies did not interfere with the detection of spironolactone
      and furosemide; therefore, the assay can be considered to be stability
      indicating.

PMID- 22641090
TI  - The structure of proteins.

PMID- 22641091
TI  - Importance of interplane coupling on the magnetic phases of quasi-two-dimensional
      tantalites.
AB  - We propose a three-dimensional model to describe magnetic interactions in a class
      of tantalite compounds of compositions A(x)A'(1-x)Ta(2)O(6), with A,A' = Fe, Co
      or Ni. Due to the quasi-two-dimensional nature of the magnetism in these
      compounds, experimental data have been previously interpreted using two
      dimensional models. These are anisotropic Heisenberg models or Ising models and
      include competing exchange interactions from different neighbors. Taking into
      account all the relevant exchange terms, which include interplane interactions,
      we show that the latter allows us to understand the various low-temperature
      magnetic phases observed by neutron diffraction in this family of compounds. This
      is done by studying the eigenvalues of the exchange-interaction matrix in
      wavevector space for different sets of coupling parameters, of which those
      relative to in-plane interactions have been obtained from high-temperature series
      analysis of the magnetic susceptibility. This approach is rather general and the
      model presented here is directly applicable to isostructural compounds like
      ASb(2)O(6).

PMID- 22641092
TI  - Nilotinib protects the murine liver from ischemia/reperfusion injury.
AB  - BACKGROUND & AIMS: The mitogen-activated protein kinases (MAPKs), c-Jun N
      terminal kinase (JNK), and p38, mediate liver ischemia/reperfusion (I/R) injury
      via cell death and inflammatory cytokine expression, respectively. Nilotinib is
      an orally available receptor tyrosine kinase inhibitor used for chronic
      myelogenous leukemia that also has in vitro activity against JNK and p38. In this
      study, we examine its therapeutic potential against hepatic I/R injury. METHODS:
      The effects of nilotinib on liver I/R injury were tested using a murine model of
      warm, segmental liver I/R. Serum ALT was measured and livers were analyzed by
      histology, RT-PCR, Western blot, and flow cytometry. The in vitro effects of
      nilotinib on hepatocyte and non-parenchymal cell (NPC) MAPK activation and
      cytokine production were also tested. RESULTS: Mice receiving nilotinib had
      markedly lower serum ALT levels and less histologic injury and apoptosis
      following liver I/R. Nilotinib did not inhibit its known receptor tyrosine
      kinases. Nilotinib lowered intrahepatic expression of IL-1beta, IL-6, MCP-1, and
      MIP-2 and systemic levels of IL-6, MCP-1, and TNF. Nilotinib reduced NPC
      activation of p38 MAPK signaling and decreased the recruitment of inflammatory
      monocytes and their production of TNF. Nilotinib attenuated JNK phosphorylation
      and hepatocellular apoptosis. In vitro, nilotinib demonstrated direct inhibition
      of JNK activation in isolated hepatocytes cultured under hypoxic conditions, and
      blocked activation of p38 MAPK and cytokine production by stimulated NPCs.
      CONCLUSIONS: Nilotinib lowers both liver JNK activation and NPC p38 MAPK
      activation and may be useful for ameliorating liver I/R injury in humans.

PMID- 22641093
TI  - Hepatitis E virus-induced severe myositis.

PMID- 22641094
TI  - A hedgehog survival pathway in 'undead' lipotoxic hepatocytes.
AB  - BACKGROUND & AIMS: Ballooned hepatocytes in non-alcoholic steatohepatitis (NASH)
      generate sonic hedgehog (SHH). This observation is consistent with a cellular
      phenotype in which the cell death program has been initiated but cannot be
      executed. Our aim was to determine whether ballooned hepatocytes have potentially
      disabled the cell death execution machinery, and if so, can their functional
      biology be modeled in vitro. METHODS: Immunohistochemistry was performed on human
      NASH specimens. In vitro studies were performed using HuH-7 cells with shRNA
      targeted knockdown of caspase 9 (shC9 cells) or primary hepatocytes from caspase
      3(-/-) mice. RESULTS: Ballooned hepatocytes in NASH display diminished expression
      of caspase 9. This phenotype was modeled using shC9 cells; these cells were
      resistant to lipoapoptosis by palmitate (PA) or lysophosphatidylcholine (LPC)
      despite lipid droplet formation. During lipid loading by either PA or LPC, shC9
      cells activate JNK which induces SHH expression via AP-1. An autocrine hedgehog
      survival signaling pathway was further delineated in both shC9 and caspase 3(-/-)
      cells during lipotoxic stress. CONCLUSIONS: Ballooned hepatocytes in NASH
      downregulate caspase 9, a pivotal caspase executing the mitochondrial pathway of
      apoptosis. Hepatocytes engineered to reduce caspase 9 expression are resistant to
      lipoapoptosis, in part, due to a hedgehog autocrine survival signaling pathway.

PMID- 22641095
TI  - p53/p66Shc-mediated signaling contributes to the progression of non-alcoholic
      steatohepatitis in humans and mice.
AB  - BACKGROUND & AIMS: The tumor suppressor p53 is a primary sensor of stressful
      stimuli, controlling a number of biologic processes. The aim of our study was to
      examine the roles of p53 in non-alcoholic steatohepatitis (NASH). METHODS: Male
      wild type and p53-deficient mice were fed a methionine- and choline-deficient
      diet for 8 weeks to induce nutritional steatohepatitis. mRNA expression profiles
      in normal liver samples and liver samples from patients with non-alcoholic liver
      disease (NAFLD) were also evaluated. RESULTS: Hepatic p53 and p66Shc signaling
      was enhanced in the mouse NASH model. p53 deficiency suppressed the enhanced
      p66Shc signaling, decreased hepatic lipid peroxidation and the number of
      apoptotic hepatocytes, and ameliorated progression of nutritional
      steatohepatitis. In primary cultured hepatocytes, transforming growth factor
      (TGF)-beta treatment increased p53 and p66Shc signaling, leading to exaggerated
      reactive oxygen species (ROS) accumulation and apoptosis. Deficient p53 signaling
      inhibited TGF-beta-induced p66Shc signaling, ROS accumulation, and hepatocyte
      apoptosis. Furthermore, expression levels of p53, p21, and p66Shc were
      significantly elevated in human NAFLD liver samples, compared with results
      obtained with normal liver samples. Among NAFLD patients, those with NASH had
      significantly higher hepatic expression levels of p53, p21, and p66Shc compared
      with the group with simple steatosis. A significant correlation between
      expression levels of p53 and p66Shc was observed. CONCLUSIONS: p53 in hepatocytes
      regulates steatohepatitis progression by controlling p66Shc signaling, ROS
      levels, and apoptosis, all of which may be regulated by TGF-beta. Moreover,
      p53/p66Shc signaling in the liver appears to be a promising target for the
      treatment of NASH.

PMID- 22641096
TI  - Trace metals alter DNA repair and histone modification pathways concurrently in
      mouse embryonic stem cells.
AB  - Exposure to metals alters gene expression, changes transcription rates or
      interferes with DNA repair mechanisms. We tested a hypothesis to determine
      whether in vitro acute metal exposure, with or without recovery, alters
      epigenetic pathways in mouse embryonic stem (mES) cells. We measured cell
      viability, total and histone protein production, changes in gene expression for
      differentiation and DNA repair, and histone lysine mono-methylation (H3K27me1),
      in differentiated cells. Confluent differentiated cultures of mES cells were
      exposed to arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), lithium (Li),
      mercury (Hg), and nickel (Ni), for 1-h and 24-h, followed by a recovery period.
      The data demonstrate that maximum cell death occurred during the first few hours
      of exposure at 24-h IC50 concentrations for all metals. Prolonged in vitro
      exposure to metals at low concentrations also inhibited protein production and
      cell proliferation. Subsequently, we determined that metals alter cell
      differentiation (Oct-4 and egfr) and DNA repair mechanisms (Rad-18, Top-3a and
      Ogg-1). Interestingly, As, Cd, Hg, and Ni decreased cell proliferation to a
      greater extent than total histone protein production. Yet, at equivalent
      concentrations, As and Hg significantly decreased total histone protein
      production per cell compared to respective controls, suggesting suppression of
      repair or compensatory mechanisms involving histone pathways. And, acute exposure
      to As, Cd, Hg and Ni decreased H3K27me1 residue, when compared to control cells.
      Because activation of cellular differentiation, histone modification, and DNA
      repair are linked by common transcriptional pathways, and the data propose that
      metals alter these conduits, then it is reasonable to conclude that trace
      quantities of metals are capable of suppressing regulation of chromatin
      structure, cellular differentiation, and controlled cell proliferation in mES
      cells.

PMID- 22641097
TI  - Transcription factor Runx2 is a regulator of epithelial-mesenchymal transition
      and invasion in thyroid carcinomas.
AB  - Runx2/Cbfa1 is a member of the Runt-related transcription factor family and is an
      essential regulator of osteoblast/chondrocyte differentiation. Recently, aberrant
      expression of Runx2 and its oncogenic functions have been identified in the
      progression and metastasis of human cancers. In this study, we investigated the
      expression profile of Runx family genes in normal thyroid tissue, non-neoplastic
      but abnormal thyroid tissue, various types of thyroid tumors and representative
      human thyroid carcinoma cell lines. Using reverse transcriptase-PCR and western
      blotting, we found that Runx2 was consistently upregulated in papillary
      carcinomas (PCs) and thyroid carcinoma cell lines compared with normal thyroid
      tissue. With immunohistochemistry, we observed negative or focal immunoreactivity
      of Runx2 in the nuclei of normal thyroid follicular cells. None of the non
      neoplastic thyroid tissues, including Graves' thyroid and adenomatous goiter, had
      diffuse positivity of Runx2. Expression of Runx2 in benign follicular adenomas
      varied from negative to diffusely positive. Meanwhile, all malignant thyroid
      tumors showed some Runx2 immunopositivity. It was diffuse and intense in 83%
      (19/23) of PCs, 71% (5/7) of follicular carcinomas (FCs) and 40% (4/10) of
      undifferentiated carcinomas (UCs). In thyroid carcinoma cell lines, the MEK
      inhibitor U0126 suppressed Runx2, suggesting an association of the MAPK/ERK
      pathway with Runx2 regulation. Effective silencing of Runx2 by short interfering
      RNA (siRNA) demonstrated downregulation of EMT-related molecules (SNAI2, SNAI3
      and TWIST1), MMP2 and vasculogenic factors (VEGFA and VEGFC) in thyroid carcinoma
      cells. We also confirmed that Runx2 silencing suppresses thyroid carcinoma cell
      invasion in transwell assays. In conclusion, this study provides insight into the
      potential molecular mechanism of thyroid cancer invasion. Our data suggest that
      enhanced Runx2 is functionally linked to tumor invasion and metastasis of thyroid
      carcinoma by regulating EMT-related molecules, matrix metalloproteinases and
      angiogenic/lymphangiogenic factors.

PMID- 22641098
TI  - Intestinal epithelial cell-specific CD98 expression regulates tumorigenesis in
      Apc(Min/+) mice.
AB  - The transmembrane glycoprotein CD98 regulates integrin signaling that in turn
      controls cell proliferation and survival. CD98 expression is upregulated in
      various carcinomas, including colorectal cancer. Recently, by generating gain-
      and loss-of-function mouse models featuring genetic manipulation of CD98
      expression specifically in intestinal epithelial cells (IECs), we have explored
      the crucial role of CD98 in the regulation of intestinal homeostasis and
      inflammation-associated tumorigenesis. In the present study, we investigated the
      contribution of CD98 to intestinal tumorigenesis in Apc(Min/+) mice and the
      underlying mechanism of action. Mice featuring IEC-specific CD98 overexpression
      (Tg animals) were crossed with Apc(Min/+) mice, and the characteristics of
      intestinal adenoma formation were assessed. Compared with Apc(Min/+) mice,
      Tg/Apc(Min/+) animals exhibited increases in both intestinal tumor incidence and
      tumor size; these parameters correlated with enhanced proliferation and decreased
      apoptosis of IECs. IEC-specific CD98 overexpression resulted in increased
      synthesis of the oncogenic proteins c-myc and cyclin-D1 in Apc(Min/+) mice,
      independently of the Wnt-APC-beta-catenin pathway, suggesting the implication of
      CD98 overexpression-mediated Erk activation. IEC-specific CD98 overexpression
      enhanced the production of proinflammatory cytokines and chemokines that are
      crucial for tumorigenesis. We validated our results in mice exhibiting IEC
      specific CD98 downregulation (CD98(flox/+)VillinCre animals). IEC-specific CD98
      downregulation efficiently attenuated tumor incidence and growth in Apc(Min/+)
      mice. The reduction of intestinal tumorigenesis upon IEC-specific CD98
      downregulation was caused by the attenuation of IEC proliferation and
      cytokine/chemokine production. In conclusion, we show that CD98 exerts an
      oncogenic activity in terms of intestinal tumorigenesis, via an ability to
      regulate tumor growth and survival.

PMID- 22641099
TI  - Liver X receptor alpha-mediated regulation of lipogenesis by core and NS5A
      proteins contributes to HCV-induced liver steatosis and HCV replication.
AB  - Molecular mechanisms contributing to hepatitis C virus (HCV)-associated steatosis
      are not well established, although HCV gene expression has been shown to alter
      host cell cholesterol/lipid metabolism. As liver X receptors (LXRs) play a role
      as key modulators of metabolism signaling in the development of steatosis, we
      aimed to investigate in an HCV in vitro model the effect of HCV NS5A protein,
      core protein, and viral replication on the intracellular lipid accumulation and
      the LXRalpha-regulated expression of lipogenic genes. The effects of LXRalpha
      siRNA or agonist GW3965 treatment on lipogenesis and HCV replication capacity in
      our HCV replicon system were also examined. NS5A- and core-expressing cells and
      replicon-containing cells exhibited an increase of lipid accumulation by inducing
      the gene expression and the transcriptional activity of LXRalpha, and leading to
      an increased expression of its lipogenic target genes sterol regulatory element
      binding protein-1c, peroxisome proliferator-activated receptor-gamma, and fatty
      acid synthase. Transcriptional induction by NS5A protein, core protein, and viral
      replication occurred via LXR response element activation in the lipogenic gene
      promoter. No physical association between HCV proteins and LXRalpha was observed,
      whereas NS5A and core proteins indirectly upregulated LXRalpha through the
      phosphatidylinositol 3-kinase pathway. Finally, it was found that LXRalpha
      knockdown or agonist-mediated LXRalpha induction directly regulated HCV-induced
      lipogenesis and HCV replication efficiency in replicon-containing cells.
      Combined, our data suggest that LXRalpha-mediated regulation of lipogenesis by
      core and NS5A proteins may contribute to HCV-induced liver steatosis and to the
      efficient replication of HCV.

PMID- 22641101
TI  - Targeting COX-2 and EP4 to control tumor growth, angiogenesis, lymphangiogenesis
      and metastasis to the lungs and lymph nodes in a breast cancer model.
AB  - We reported that cyclo-oxygenase (COX)-2 expression in human breast cancer
      stimulated cancer cell migration and invasiveness, production of vascular
      endothelial growth factor (VEGF)-C and lymphangiogenesis in situ, largely from
      endogenous PGE2-mediated stimulation of prostaglandin E (EP)1 and EP4 receptors,
      presenting them as candidate therapeutic targets against lymphatic metastasis. As
      human breast cancer xenografts in immuno-compromised mice have limitations for
      preclinical testing, we developed a syngeneic murine breast cancer model of
      spontaneous lymphatic metastasis mimicking human and applied it for mechanistic
      and therapeutic studies. We tested the roles of COX-2 and EP receptors in VEGF-C
      and -D production by a highly metastatic COX-2 expressing murine breast cancer
      cell line C3L5. These cells expressed all EP receptors and produced VEGF-C and 
      D, both inhibited with COX-2 inhibitors or EP4 (but not EP1, EP2 or EP3)
      antagonists. C3H/HeJ mice, when implanted SC in both inguinal regions with C3L5
      cells suspended in growth factor-reduced Matrigel, exhibited rapid tumor growth,
      tumor-associated angiogenesis and lymphangiogenesis (respectively measured with
      CD31 and LYVE-1 immunostaining), metastasis to the inguinal and axillary lymph
      nodes and the lungs. Chronic oral administration of COX-1/COX-2 inhibitor
      indomethacin, COX-2 inhibitor celecoxib and an EP4 antagonist ONO-AE3-208, but
      not an EP1 antagonist ONO-8713 at nontoxic doses markedly reduced tumor growth,
      lymphangiogenesis, angiogenesis, and metastasis to lymph nodes and lungs.
      Residual tumors in responding mice revealed reduced VEGF-C and -D proteins, AkT
      phosphorylation and increased apoptotic/proliferative cell ratios consistent with
      blockade of EP4 signaling. We suggest that EP4 antagonists deserve clinical
      testing for chemo-intervention of lymphatic metastasis in human breast cancer.

PMID- 22641100
TI  - CCL2 disrupts the adherens junction: implications for neuroinflammation.
AB  - Alterations to blood-brain barrier (BBB) adhesion molecules and junctional
      integrity during neuroinflammation can promote central nervous system (CNS)
      pathology. The chemokine CCL2 is elevated during CNS inflammation and is
      associated with endothelial dysfunction. The effects of CCL2 on endothelial
      adherens junctions (AJs) have not been defined. We demonstrate that CCL2
      transiently induces Src-dependent disruption of human brain microvascular
      endothelial AJ. beta-Catenin is phosphorylated and traffics from the AJ to PECAM
      1 (platelet endothelial cell adhesion molecule-1), where it is sequestered at the
      membrane. PECAM-1 is also tyrosine-phosphorylated, an event associated with
      recruitment of the phosphatase SHP-2 (Src homology 2 domain-containing protein
      phosphatase) to PECAM-1, beta-catenin release from PECAM-1, and reassociation of
      beta-catenin with the AJ. Surface localization of PECAM-1 is increased in
      response to CCL2. This may enable the endothelium to sustain CCL2-induced
      alterations in AJ and facilitate recruitment of leukocytes into the CNS. Our
      novel findings provide a mechanism for CCL2-mediated disruption of endothelial
      junctions that may contribute to BBB dysfunction and increased leukocyte
      recruitment in neuroinflammatory diseases.

PMID- 22641102
TI  - Iridium-catalyzed reaction of enones with alcohols affording 1,3-diketones.
AB  - An iridium-catalyzed coupling reaction of alcohols with enones has been
      successfully developed providing access to 1,3-diketones with high selectivity in
      good yields. This reaction provides an atom-economical route to 1,3-diketones
      from readily available alcohols.

PMID- 22641103
TI  - Material properties of photomechanical infrared receptors in pyrophilous
      Melanophila beetles and Aradus bugs.
AB  - Jewel beetles of the genus Melanophila and some pyrophilous species of the flat
      bugs genus Aradus show a pyrophilous behaviour and have developed so-called
      photomechanical infrared (IR) receptors. In a spherical photomechanical IR
      sensillum incoming IR radiation is converted into micromechanical action, finally
      stimulating the dendritic tip of a mechanosensitive sensory cell. The tip is
      located inside a tiny cuticular sphere with a diameter of about 12 MUm. The
      material properties of the different cuticular components of this sphere are of
      great importance for stimulus generation. We measured the modulus and hardness of
      the outer exocuticular shell of the sphere and the mesocuticle inside the core.
      Measurements were made by nanoindentation at sensilla which were partly cut open
      under dry as well as under rewetted (i.e. quasi-natural) conditions. We found
      that in the rewetted sensilla the outer exocuticular shell of the sphere in the
      Melanophila sensillum is about 50% harder and 20% stiffer than reference
      exocuticle, and that in both species especially the rewetted mesocuticle of the
      inner core of the IR sensilla is significantly softer (about 80% in Melanophila)
      and more compliant (about 90% also in Melanophila) than the reference
      mesocuticle. The findings can be interpreted as special adaptations of the
      cuticular microdomains of photomechanical infrared sensilla to enhance
      thermomechanical performance and, thereby, sensitivity.

PMID- 22641104
TI  - Diethylene glycol functionalized self-assembling peptide nanofibers and their
      hydrophobic drug delivery potential.
AB  - Self-assembling peptide nanofibers have emerged as important nanobiomaterials,
      with such applications as delivery of therapeutic agents and vaccines,
      nanofabrication and biomineralization, tissue engineering and regenerative
      medicine. Recently a new class of self-assembling peptides has been introduced,
      which takes into consideration amino acid pairing (AAP) strategies in the peptide
      sequence design. Even though these peptides have shown promising potential in the
      design of novel functional biomaterials, they have a propensity to initiate
      uncontrollable aggregation and be degraded by proteolytic enzymes. These present
      the most significant challenge in advancing self-assembling peptides for in vitro
      and in vivo applications. Functionalizing biomaterials with polyethylene glycol
      (PEG) has been shown to surmount such problems. Here the results of conjugating
      diethylene glycol (DEG), a short segment of PEG, to one of the AAP peptides,
      AAP8, with eight amino acids in sequence, are reported. The results indicate that
      incorporation of DEG into the peptide sequence modulates fiber self-assembly
      through creating more aligned and uniform nanostructures. This is associated with
      increasing solubility, stability, and secondary structure beta-sheet content of
      the peptide. The DEG conjugate of AAP8 also shows reduced cellular cytotoxicity.
      Functionalization of AAP8 improves the capability of the peptide to stabilize and
      deliver a hydrophobic anticancer compound, ellipticine, in aqueous solution,
      consequently inducing greater cytotoxicity to lung carcinoma cells over a
      relatively long time, compared with non-functionalized AAP8. The presented
      functionalized peptide and its drug delivery application indicate a potentially
      useful design strategy for novel self-assembling peptide biomaterials for
      biotechnology and nanomedicine.

PMID- 22641105
TI  - Oriented lamellar silk fibrous scaffolds to drive cartilage matrix orientation:
      towards annulus fibrosus tissue engineering.
AB  - A novel design of silk-based scaffold is developed using a custom-made winding
      machine, with fiber alignment resembling the anatomical criss-cross lamellar
      fibrous orientation features of the annulus fibrosus of the intervertebral disc.
      Crosslinking of silk fibroin fibers with chondroitin sulphate (CS) was introduced
      to impart superior biological functionality. The scaffolds, with or without CS,
      instructed alignment of expanded human chondrocytes and of the deposited
      extracellular matrix while supporting their chondrogenic redifferentiation. The
      presence of CS crosslinking could not induce statistically significant changes in
      the measured collagen or glycosaminoglycan content, but resulted in an increased
      construct stiffness. By offering the combined effect of cell/matrix alignment and
      chondrogenic support, the silk fibroin scaffolds developed with precise fiber
      orientation in lamellar form represent a suitable substrate for tissue
      engineering of the annulus fibrosus part of the intervertebral disc.

PMID- 22641106
TI  - Functional porous hydrogels to study angiogenesis under the effect of controlled
      release of vascular endothelial growth factor.
AB  - Angiogenesis occurs through a cascade of events controlled by complex multiple
      signals that are orchestrated according to specific spatial patterns and temporal
      sequences. Vascularization is a central issue in most tissue engineering
      applications. However, only a better insight into spatio-temporal signal
      presentation can help in controlling and guiding angiogenesis in vivo. To this
      end, versatile and accessible material platforms are required in order to study
      angiogenic events in a systematic way. In this work we report a three-dimensional
      porous polyethylene glycol (PEG) diacrylate hydrogel bioactivated with heparin
      that is able to deliver vascular endothelial growth factor (VEGF) in a sustained
      and controlled manner. The efficiency of the material has been tested both in
      vitro and in vivo. In particular, the VEGF released from the hydrogel induces
      cell proliferation when tested on HUVECs, retains its bioactivity up to 21days,
      as demonstrated by Matrigel assay, and, when implanted on a chorion allantoic
      membrane, the hydrogel shows superior angiogenic potential in stimulating new
      vessel formation compared with unfunctionalized hydrogels. Moreover, in the light
      of potential tissue regeneration studies, the proposed hydrogel has been modified
      with adhesion peptides (RGD) to enable cell colonization. The porous hydrogel
      reported here can be used as a valid tool to characterize angiogenesis, and,
      possibly, other biological processes, in different experimental set-ups.

PMID- 22641107
TI  - Random parasite encounters coupled with condition-linked immunity of hosts
      generate parasite aggregation.
AB  - Parasite aggregation is viewed as a natural law in parasite-host ecology but is a
      paradox insofar as parasites should follow the Poisson distribution if hosts are
      encountered randomly. Much research has focused on whether parasite aggregation
      in or on hosts is explained by aggregation of infective parasite stages in the
      environment, or by heterogeneity within host samples in terms of host responses
      to infection (e.g., through representation of different age classes of hosts). In
      this paper, we argue that the typically aggregated distributions of parasites may
      be explained simply. We propose that aggregated distributions can be derived from
      parasites encountering hosts randomly, but subsequently by parasites being 'lost'
      from hosts based on condition-linked escape or immunity of hosts. Host condition
      should be a normally distributed trait even among otherwise homogeneous sets of
      hosts. Our model shows that mean host condition and variation in host condition
      have different effects on the different metrics of parasite aggregation. Our
      model further predicts that as host condition increases, parasites become more
      aggregated but numbers of attending parasites are reduced overall and this is
      important for parasite population dynamics. The effects of deviation from random
      encounter are discussed with respect to the relationship between host condition
      and final parasite numbers.

PMID- 22641109
TI  - Endoscopic sphincterotomy combined with large balloon dilation for removal of
      large bile duct stones.
AB  - BACKGROUND/AIMS: Recently, there have been sporadic reports of lithotomy using
      endoscopic sphincterotomy combined with large balloon dilation (EPLBD) against
      large or multiple bile duct stones. However, there are not many reports so far
      concerning this procedure. Therefore, we decided to discuss the results of EPLBD
      against large or multiple bile duct stones. METHODOLOGY: Stone retrieval using
      EPLBD was performed with 59 patients of choledocholithiasis, A) with 13 mm or
      more in shortest dimension, or B) multiple (>=3) bile duct stones, with the
      smallest more than 10 mm in shortest dimension. The papilla treated with
      endoscopic sphincterotomy (EST) was dilated using a 12-20 mm balloon suitable for
      the biliary ductal size. RESULTS: The success rate for the first lithotomy for
      choledocholithiasis was 83.1% (49/59). The final lithotomy rate was 100% (59/59).
      The time required for lithotomy was 43.7 (12-125) minutes and the number of
      treatment was 1.3 (1-4) on average. Lithotripsy was needed in 13.6% (8/59). The
      incidence of coincidental events associated with the procedure was 6.8% (4/59).
      No pancreatitis was noted. CONCLUSIONS: An endoscopic treatment using EST plus
      large balloon dilation against large or multiple bile duct stones was suggested
      to be safe and effective.

PMID- 22641110
TI  - Percutaneous transhepatic biliary stenting vs. surgical bypass in advanced
      malignant biliary obstruction: cost- effectiveness analysis.
AB  - BACKGROUND/AIMS: This study aims to compare the clinical outcomes and costs
      between percutaneous transhepatic biliary stenting (PTBS) and surgical bypass.
      METHODOLOGY: We randomly assigned 142 patients with unresectable malignant
      biliary obstruction between 2005 and 2010 to receive PTBS or surgical bypass as
      palliative treatment. PTBS was successfully performed in 70 patients who formed
      the PTBS group (failed in 7 patients). Sixty five patients underwent surgical
      bypass treatment. Additional gastrojejunostomy was performed in five patients.
      The effectiveness of biliary drainage, hospital stay, complications, cost,
      survival time and mortality were compared. RESULTS: Patients in PTBS group had
      shorter hospital stay and lower initial and overall expense than the surgical
      group (p<0.05). There was no significant difference in effectiveness of biliary
      drainage (p=0.9307) or survival time between two groups (p=0.4826). Early
      complications of PTBS group was significantly lower than surgical group (3/75 vs.
      11/65, p=0.0342). Late complication in PTBS group did not differ significantly
      from surgical group (9/70 vs. 6/65, p=0.6823). The survival curves in the two
      groups showed no significant difference (p=0.1032). CONCLUSIONS: PTBD is a better
      palliative treatment than surgical bypass for unresectable malignant biliary
      obstruction for its high effectiveness of biliary drainage and acceptable expense
      and complication.

PMID- 22641111
TI  - A broad-spectrum analysis of the effects of teflubenzuron exposure on the
      biochemical activities and microbial community structure of soil.
AB  - We evaluated the response of soil bacteria to applications of the insecticide
      teflubenzuron at the field rate dosage (FR; 0.15 mg/kg of soil) and at a higher
      dosage (10*FR; 1.5 mg/kg of soil). When applied at the FR dosage, teflubenzuron
      had no effect on several biochemical parameters of the soil, including substrate
      induced respiration (SIR), dehydrogenase (DHA) and phosphatase activities (PHOS),
      and N-NO(3)(-) and N-NH(4)(+) concentrations. Additionally, no differences were
      observed in the culturable fraction of the soil bacteria (the number of
      heterotrophic, nitrifying, denitrifying and N(2)-fixing bacteria; the growth
      strategy; the ecophysiological and colony development indices; and the
      physiological state). In contrast, treatment with the 10*FR dosage of the
      insecticide significantly increased SIR, DHA, PHOS and N-NH(4)(+) levels and the
      number of heterotrophic and denitrifying bacteria. Decreases in urease activity
      (URE) and the number of nitrifying and N(2)-fixing bacteria were also observed. A
      phospholipid fatty acid (PLFA) method-based analysis of the entire soil
      microorganism population revealed that teflubenzuron treatment affected the total
      fatty acid level as well as those considered to be of Gram-positive bacteria,
      Gram-negative bacteria and fungi. This effect was observed on days 1 and 14 post
      treatment. A principal component analysis (PCA) of the PLFAs showed that
      teflubenzuron treatment significantly shifted the microbial community structure;
      however, all of the observed effects were transient. Studies on the degradation
      of teflubenzuron revealed that this process is characterised by a short lag phase
      and a rate constant (k) of 0.020/day. This degradation rate follows first-order
      kinetics, and the DT50 was 33.5 days. This is the first study that thoroughly
      examines the functional and structural status of both the culturable and non
      culturable fractions of the soil microbial community after teflubenzuron
      application.

PMID- 22641112
TI  - Possible use of heterospecific food-associated calls of macaques by sika deer for
      foraging efficiency.
AB  - Heterospecific communication signals sometimes convey relevant information for
      animal survival. For example, animals use or eavesdrop on heterospecific alarm
      calls concerning common predators. Indeed, most observations have been reported
      regarding anti-predator strategies. Use of heterospecific signals has rarely been
      observed as part of a foraging strategy. Here, I report empirical evidence,
      collected using playback experiments, showing that Japanese sika deer, Cevus
      nippon, use heterospecific food calls of Japanese macaques, Macaca fuscata yakui,
      for foraging efficiency. The deer and macaques both inhabit the wild forest of
      Yakushima Island with high population densities and share many food items.
      Anecdotal observations suggest that deer often wait to browse fruit falls under
      the tree where a macaque group is foraging. Furthermore, macaques frequently
      produce food calls during their foraging. If deer effectively obtain fruit from
      the leftovers of macaques, browsing fruit fall would provide a potential benefit
      to the deer, and, further, deer are likely to associate macaque food calls with
      feeding activity. The results showed that playback of macaque food calls under
      trees gathered significantly more deer than silence control periods. These
      results suggest that deer can associate macaque food calls with foraging
      activities and use heterospecific calls for foraging efficiency.

PMID- 22641108
TI  - Small-fibre neuropathies--advances in diagnosis, pathophysiology and management.
AB  - Small-fibre neuropathy (SFN), a disorder of thinly myelinated Adelta-fibres and
      unmyelinated C-fibres, is clinically characterized by neuropathic pain symptoms
      and autonomic complaints. Diagnosis of SFN is challenging as the clinical picture
      can be difficult to interpret and results from nerve conduction studies are often
      normal. In cases of suspected SFN, measurement of intraepidermal nerve fibre
      density and/or analysis of quantitative sensory testing can enable diagnosis. New
      diagnostic techniques (including measurement of nerve fibre density using corneal
      confocal microscopy, and nociceptive evoked potentials) may contribute to the
      diagnostic work-up. SFN can be associated with systemic diseases such as immune
      mediated disorders, but remains idiopathic in a substantial proportion of
      patients. Gain-of-function variants in the Na(v)1.7 sodium channel have recently
      been found in nearly 30% of patients with idiopathic SFN, but the mechanisms of
      axonal degeneration in the disorder remain under investigation. Identification of
      the systemic diseases underlying SFN will enable development of drugs that target
      affected pathways to improve the management of neuropathic pain and autonomic
      dysfunction. In this Review, we discuss recent advances in the diagnosis and
      pathophysiology of SFN, highlighting how improved understanding of these aspects
      of the disorder will contribute to better patient management.

PMID- 22641113
TI  - Pro- and anti-inflammatory cytokine expression in carp blood and head kidney
      leukocytes exposed to cyanotoxin stress--an in vitro study.
AB  - Cyanotoxins are toxic, secondary metabolites produced by different species of
      cyanobacteria that are present all over the world in aquatic environments. No
      data are available about the molecular mechanisms underlying the stress
      associated with exposure of fish immune cells to low concentrations of
      cyanotoxins. The purpose of this study was to determine whether the expression of
      cytokines that underlie immune regulation are changed after incubation of fish
      leukocytes with pure cyanotoxins: microcystin- LR (MC-LR), anatoxin-a (Antx-a),
      or an extract containing Antx-a. The study investigated the relative gene
      expression of four important cytokines, IL-1beta, TNF-alpha, IL-10, and TGF-beta,
      in carp head kidney and blood leukocytes exposed to toxins at concentrations of
      0.01 or 0.1 MUg/ml for 4 h. The data showed that pure toxins could induce
      dysregulation of pro-/anti-inflammatory cytokine expression. Expression of
      cytokine IL-1 beta was highly upregulated following Antx-a exposure, whereas MC
      LR induced merely moderate reactions. The expression of TNF-alpha mRNA was
      significantly suppressed in blood and head kidney cells incubated with toxins at
      the higher concentration. These results showed that pure toxins dysregulated the
      expression of pro-inflammatory cytokines IL-1beta and TNF-alpha more promptly
      than the anti-inflammatory cytokines TGF-beta and IL-10. In contrast, the studies
      demonstrated a clearly downward trend of pro-inflammatory cytokines and an upward
      trend of anti-inflammatory cytokines in leukocytes exposed to an extract
      containing defined concentrations of Antx-a. This study suggests that cyanotoxins
      present in aquatic environments may exert immunotoxic effects by altering the
      transcription of important mediators of the fish immune system.

PMID- 22641115
TI  - Physical properties and crystal chemistry of Ce2Ga12Pt.
AB  - Single crystals of the new ternary compound Ce(2)Ga(12)Pt were prepared by the
      self-flux technique. The crystal structure with the space group P4/nbm was
      established from single crystal x-ray diffraction data and presents a derivative
      of the LaGa(6)Ni(0.6) prototype. Magnetic susceptibility measurements show Curie
      Weiss behaviour due to local Ce(3+) moments. At high temperatures, the magnetic
      anisotropy is dominated by the crystal-electric-field (CEF) effect with the easy
      axis along the crystallographic c direction. Ce(2)Ga(12)Pt undergoes two
      antiferromagnetic phase transitions at T(N,1) = 7.3 K and T(N,2) = 5.5 K and
      presents several metamagnetic transitions for the magnetic field along c.
      Specific-heat measurements prove the bulk nature of these magnetic transitions
      and reveal a doublet CEF ground state. The 4f contribution to the resistivity
      shows a broad maximum at T(max) ~ 85 K due to Kondo scattering off the CEF ground
      state and excited levels.

PMID- 22641114
TI  - Pathogen recognition and mechanisms in Atlantic cod (Gadus morhua) head kidney
      cells: bacteria (LPS) and virus (poly I:C) signals through different pathways and
      affect distinct genes.
AB  - Understanding pathogen recognition and mechanisms in Atlantic cod are of
      significant importance for both basic research on wild populations and health
      management in aquaculture. A microarray approach was utilized to search for
      effects of viral (polyinosinic acid:polycytidylic acid), bacterial
      (lipopolysaccharide) and polyclonal activator (phytohaemoagglutinin) stress in
      Atlantic cod head kidney cells. LPS cell activation increased mRNA expression of
      interleukin 8; interleukin-1beta; cyclooxygenase 2; leukocyte derived chemotaxin
      2; carboxyl-esterase 2 and environmental biomarker cytochrome P450 1A. Mitogen
      activated protein kinase p38 and cathepsin F were down regulated by LPS. The
      antiviral responses induced by double stranded RNA clearly increased
      transcription of Toll like receptor 3 and interferon stimulating gene 15. The
      phytohaemoagglutinin response seemed to be more non-specific. Special for the
      phytohaemoagglutinin induction was the increase in major histocompatibility
      complex class I. CC chemokine type 2 mRNA expression was increased by
      phytohaemoagglutinin, lipopolysaccharide and polyinosinic acid:polycytidylic
      acid, while mitogen activated protein kinase p38 and leukocyte derived chemotaxin
      2 were down regulated by phytohaemoagglutinin. Oxidative stress related genes
      like catalase and glutaredoxin and the anti-apoptotic gene Bcl-2 showed no
      transcriptional changes compared to control in any of the treatments. Eicosanoids
      like prostaglandin 2, leukotriene B4 and B5 were constitutively produced by cod
      head kidney cells in vitro. The most remarkable feature of eicosanoid secretion
      is the higher production of leukotrienes against prostaglandins, indicating that
      the lipooxygenase pathway is preferred over the cyclooxygenase pathway. Although
      there were no significant differences in eicosanoid secretion between the groups,
      polyinosinic acid:polycytidylic acid showed a clear tendency to increase the
      levels of leukotriene B4 and B5. This study reveals distinct signatures of
      bacteria and virus transcriptional responses in cod head kidney cells. In
      addition, the novel finding that cytochrome P450 1A was upregulated during the
      antibacterial response indicates a connection between immunity and aryl
      hydrocarbon receptor activation in Atlantic cod.

PMID- 22641116
TI  - Hybridization of inorganic nanoparticles and polymers to create regular and
      reversible self-assembly architectures.
AB  - Inorganic nanoparticles (NPs) with diversified functionalities are promising
      candidates in future optoelectronic and biomedical applications, which greatly
      depend on the capability to arrange NPs into higher-order architectures in a
      controllable way. This issue is considered to be solved by means of self
      assembly. NPs can participate in self-assembly in different manners, such as
      smart self-organization with blended molecules, as the carriers of host molecules
      for assembly and disassembly with guest molecules, as netpoints to endow the
      architectures specific functionalities, and so forth. To enhance the structural
      stability of the as-prepared assembly architectures, polymers have been utilized
      to create NP-polymer composites. Meanwhile, such a strategy also demonstrates the
      possibility of integrating the functionalities of NPs and/or polymers by forming
      regular architectures. The emerging interest in the current optoelectronic and
      biological areas strongly demands intelligent nanocomposites, which are produced
      by combination of the excellent functionalities of NPs and the responsiveness of
      polymers. On the basis of the recent progress in fabricating NP-polymer
      composites, this critical review summarizes the development of new methods for
      fabricating regular self-assembly architectures, highlights the reversible
      assembly and disassembly behavior, and indicates the potential applications.

PMID- 22641117
TI  - Respiratory toxicities of nanomaterials -- a focus on carbon nanotubes.
AB  - Carbon nanotubes (CNT) are emblematic nanomaterials, presenting unique physico
      chemical properties, such as mechanical, thermal, or electrical conductivity,
      that have led to a large number of actual applications and uses, as well as
      (future) developments in aerospace, automobiles, nanoelectronic, or nanomedicine.
      CNT are currently used in many devices (computers, aircraft airframe, and
      sporting goods such as tennis rackets, bicycles, golf irons) and have also
      emerged as efficient drug delivery carriers in the biomedical and drug delivery
      fields[1]. Because of these actual and future applications, there's an increasing
      concern regarding the consequences that could result from human exposure to CNT,
      particularly at the respiratory level, since it represents a major route of
      exposure to nanomaterials. This review will highlight the advancement in the
      actual knowledge on lung toxicities of CNT, and try to better understand the
      underlying biological mechanisms, as well as the importance of physico-chemical
      determinants directly related to CNT characteristics.

PMID- 22641118
TI  - The Rio Declaration: addressing the health inequalities experienced by people
      with intellectual disabilities.

PMID- 22641119
TI  - The involvement of the antennae in mediating the brood influence on circadian
      rhythms in "nurse" honey bee (Apis mellifera) workers.
AB  - Age-related division of labor in honey bees is associated with plasticity in
      circadian rhythms. Forager bees that are typically older than 3 weeks of age show
      strong behavioral and molecular circadian rhythms with higher activity during the
      day. Younger bees that typically care for ("nurse") the brood are active around
      the clock with similar brain clock gene levels throughout the day. However,
      nurses that are caged on brood-less combs inside or outside the hive show robust
      circadian rhythms with higher activity during the day, suggesting that direct
      contact with the brood mediates the plasticity in the circadian system. The
      nature of the brood signals affecting the workers' circadian system and the
      modalities by which they are detected are unknown. Given that the antennae are
      pivotal sensory organs in bees, we hypothesized that they are involved in
      mediating the brood influence on the plasticity in circadian rhythms. The
      flagella of the antennae are densely covered with diverse sensory structures able
      to detect a wide range of signals. To test our hypothesis, we removed the
      flagella of nurses and observed their behavior in isolation and in free-foraging
      colonies. We found that individually-isolated flagella-less bees under constant
      laboratory conditions show robust circadian rhythms in locomotor activity. In
      observation hives, flagella-less bees cared for the brood, but were more active
      during the day. By contrast, sham-treated bees were active around the clock as
      typical of nurses. Detailed video recordings showed that the brood-tending
      behavior of flagella-less and sham-treated bees is similar. These observations
      suggest that the difference in the patterns of brood care activity is not because
      the flagella-less bees did not contact the brood. Our results suggest that nurses
      are able to find the brood in the dark environment of the hive without their
      flagella, perhaps by using other sensory organs. The higher activity of flagella
      less bees during the day further suggests that the flagella are involved in
      mediating the brood signals modulating plasticity in the circadian system.

PMID- 22641120
TI  - Establishing and analyzing the design space in the development of direct
      compression formulations by gene expression programming.
AB  - PURPOSE: In this paper we have evaluated the gene expression programming (GEP)
      methodology for modeling the effect of different variables (continuous and
      nominal) and their interactions on the properties of direct compression
      formulations. METHODS: The effect of four variables was studied; variety of
      diluents, type and percentage of drug and maximum compression force, on the
      mechanical and drug release properties of direct compression tablets. The
      generated database (36 formulations) was used for mathematical and GEP modeling.
      RESULTS: GEP has been shown to have a high accuracy in prediction for four out
      five outputs studied including friability which had no replicate measurements.
      Compared to the traditional statistical treatment GEP is less time consuming and
      gives equations which are extremely helpful in understanding the interactions of
      the different variables and for establishing the design space in the development
      of direct compression formulations. CONCLUSIONS: GEP allows similar conclusions
      than traditional statistical treatment. The helpfulness of this methodology in
      establishing the design space has been demonstrated. The knowledge derived from
      GEP can easily be increased by including additional information or new inputs,
      such as additional drugs or combinations of excipients in the data set.

PMID- 22641121
TI  - 'Formulating better medicines for children' - still paving the road.

PMID- 22641123
TI  - A technical review of flexible endoscopic multitasking platforms.
AB  - BACKGROUND: Further development of advanced therapeutic endoscopic techniques and
      natural orifice translumenal endoscopic surgery (NOTES) requires a powerful
      flexible endoscopic multitasking platform. METHODS: Medline search was performed
      to identify literature relating to flexible endoscopic multitasking platform from
      year 2004-2011 using keywords: Flexible endoscopic multitasking platform, NOTES,
      Instrumentation, Endoscopic robotic surgery, and specific names of various
      endoscopic multitasking platforms. Key articles from articles references were
      reviewed. RESULTS: Flexible multitasking platforms can be classified as either
      mechanical or robotic. Purely mechanical systems include the dual channel
      endoscope (DCE) (Olympus), R-Scope (Olympus), the EndoSamurai (Olympus), the
      ANUBIScope (Karl-Storz), Incisionless Operating Platform (IOP) (USGI), and DDES
      system (Boston Scientific). Robotic systems include the MASTER system (Nanyang
      University, Singapore) and the Viacath (Hansen Medical). The DCE, the R-Scope,
      the EndoSamurai and the ANUBIScope have integrated visual function and instrument
      manipulation function. The IOP and DDES systems rely on the conventional flexible
      endoscope for visualization, and instrument manipulation is integrated through
      the use of a flexible, often lockable, multichannel access device. The advantage
      of the access device concept is that it allows optics and instrument
      dissociation. Due to the anatomical constrains of the pharynx, systems are
      designed to have a diameter of less than 20 mm. All systems are controlled by
      traction cable system actuated either by hand or by robotic machinery. In a
      flexible system, this method of actuation inevitably leads to significant
      hysteresis. This problem will be accentuated with a long endoscope such as that
      required in performing colonic procedures. Systems often require multiple
      operators. To date, the DCE, the R-Scope, the IOP, and the Viacath system have
      data published relating to their application in human. CONCLUSION: Alternative
      forms of instrument actuation, camera control and master console ergonomics
      should be explored to improve instrument precision, sphere of action, size and
      minimize assistance required.

PMID- 22641122
TI  - An observational study of teamwork skills in shift handover.
AB  - BACKGROUND: Clinical handover (handoff, sign out) is frequently implicated as a
      cause of adverse events in hospitalised patients. Complex social interactions
      such as handover are subject to the teamwork skills of the participants and there
      is increasing evidence that the quality of teamwork in handover affects outcome.
      Teamwork skills have been assessed in one-to-one handovers but the applicability
      of these measurement tools to healthcare team shift handovers remains unproven.
      This study aimed to assess the feasibility of measurement of teamwork skills in
      shift handover and the applicability of adapted teamwork skills rating scales to
      a shift handover environment. METHODS: Morning surgical shift handovers were
      assessed for completeness of information transfer, duration, interruptions and
      handover attendance. Handover teamwork skills were evaluated using two validated
      rating scales, adapted from one-to-one handovers and intra-operative teamwork
      skill measurement. RESULTS: 50 handovers, including 306 patients were observed.
      Communication checklist completion was 97% but the quality of teamwork skills
      varied widely between handovers. There was very good concurrent validity between
      the two teamwork skill rating scales (Spearman's rho = 0.67, p < 0.001). There
      was no significant correlation between content completion, duration,
      interruptions or attendance and teamwork skill ratings. CONCLUSIONS: Teamwork
      skills vary widely between handovers and can be consistently scored using both
      rating scales. It is feasible to use adapted teamwork skill rating scales in
      shift handover and they appear to measure different constructs to traditional
      handover measures such as interruptions and communication checklist completion.
      The assessment of teamwork skills is a necessary complement to the assessment of
      completeness of information transfer when evaluating the overall quality of
      handover.

PMID- 22641124
TI  - Prognostic benefit of surgery following chemoradiotherapy for squamous cell
      carcinoma of the oesophagus.
AB  - A best evidence topic in surgery was written according to a structured protocol.
      The question addressed was whether patients who have undergone chemoradiotherapy
      (CRT) for locally advanced squamous cell carcinoma of the oesophagus benefit from
      surgical resection. 505 papers were found using the reported search, of which 5
      represented the best evidence to answer the clinical question. The authors,
      journal, date and country of publication, patient group, study type, relevant
      outcomes and results of these papers are tabulated. Of these five studies, two
      were randomised controlled trials. These demonstrated that there was no survival
      benefit in adding surgery to patients who have undergone CRT for oesophageal
      cancer. The remaining three observational studies suggest that surgery may have a
      prognostic benefit for patients who show a partial, but not complete response to
      CRT. We conclude that for patients who are complete responders to induction CRT,
      surgery adds no survival benefit. With regard to partial responders there is weak
      evidence suggesting that there may be some benefit in surgery after CRT, but
      further trials are needed to clarify the survival benefit (if any) of adding
      oesophagectomy to CRT for this sub-group.

PMID- 22641125
TI  - Unique catalysis of gold nanoparticles in the chemoselective hydrogenolysis with
      H2: cooperative effect between small gold nanoparticles and a basic support.
AB  - Gold nanoparticles on hydrotalcite act as a heterogeneous catalyst for the
      chemoselective hydrogenolysis of various allylic carbonates to the corresponding
      terminal alkenes using H(2) as a clean reductant. The combination of gold
      nanoparticles and basic supports elicited significantly unique and selective
      catalysis in the hydrogenolysis.

PMID- 22641126
TI  - Protease-activated receptor-stimulated interleukin-6 expression in endometriosis
      like lesions in an experimental mouse model of endometriosis.
AB  - The present study was undertaken to investigate the function of protease
      activated receptor (PAR) in endometriotic lesions using a mouse model of
      endometriosis. Unilateral ovariectomy (uOVX) was performed on female nude mice
      followed by intraperitoneal transplantation of a suspension mixture of
      immortalized human endometrial epithelial cells (EM-1) and stromal cells (EtsT
      499). Endometriosis-like lesions were observed mostly around the dissection site
      after transplantation. The expression of interleukin (IL)-6 and cyclooxygenase-2
      in the lesions was enhanced in uOVX mice compared to non-uOVX animals. In non
      uOVX mice, IL-6 mRNA levels were higher in lesions formed with cells that were
      pretreated with PAR1/2 agonists (thrombin, 10 U/ml and PAR2-activating peptide,
      30 uM) compared to untreated, intact cells. Peritoneal IL-6 concentrations were
      also increased in the PAR1/2 agonists-treated group. IL-6 expression induced by
      PAR activation was blocked by the treatment of cells with serine protease
      inhibitors. In cultured endometrial cells, simultaneous treatment with PAR1 and
      PAR2 agonists significantly increased the expression of IL-6. These results
      suggest that peritoneal bleeding may accelerate IL-6 expression in endometriotic
      lesions in part through the activation of PAR.

PMID- 22641127
TI  - Amelioration by the natural polyamine spermine of cartilage and bone destruction
      in rats with collagen-induced arthritis.
AB  - We investigated pharmacological properties of naturally occurring polyamines on
      cartilage and bone destruction seen in joints of rats with collagen-induced
      arthritis (CIA). Daily supplementation of spermine (SPM), but not spermidine,
      significantly inhibited increases in the hind paw volume and arthritis score in
      CIA rats, in addition to the increased mRNA expression of receptor activator of
      nuclear factor-kappaB ligand in both cartilage and synovial tissues. Histological
      analysis clearly revealed a drastic prevention by SPM of the cartilage and bone
      destruction in synovial joints of CIA rats. Particular natural polyamines would
      be beneficial for the prophylaxis of synovial joint destruction in rheumatoid
      arthritis.

PMID- 22641128
TI  - Possible modulation of the amygdala on metaplasticity deficits in the hippocampal
      CA1 field in early postnatally stressed rats.
AB  - Several lines of evidence have shown that early life experiences have a profound
      impact on fear-related behavior, but the detailed mechanisms are unknown. The
      present study examined the possible involvement of the amygdala in behavioral
      deficits associated with fear memory in a juvenile stress model, with a focus on
      hippocampal synaptic function. Adult rats exposed to footshock (FS) stress during
      the second postnatal period (2wFS group) exhibited low levels of freezing in
      response to contextual fear conditioning (CFC). The CFC-induced suppression of
      long-term potentiation (LTP) in the CA1 field was not found in the 2wFS group.
      Additionally, synaptic metaplasticity, that is, low-frequency stimulation-induced
      suppression of subsequent LTP, did not occur in the 2wFS group; instead, LTP was
      induced. These synaptic changes mimicked the impairment in metaplasticity induced
      by reversible inactivation of the basolateral amygdala (BLA). Inactivation of the
      BLA markedly decreased freezing behavior in non-FS controls, similar to the 2wFS
      group. Furthermore, extracellular signal-regulated kinase activation in the BLA
      in response to CFC did not occur in the 2wFS group. These findings suggest that
      early postnatal stress may cause long-term dysfunction of the modulatory effect
      of the amygdala on hippocampal function associated with fear memory.

PMID- 22641129
TI  - N- and L-type voltage-dependent Ca2+ channels contribute to the generation of
      after-discharges in the spinal ventral root after cessation of noxious mechanical
      stimulation.
AB  - Voltage-dependent Ca(2+) channels (VDCCs) play a crucial role in the spinal pain
      transduction. We previously reported that nociceptive mechanical stimuli to the
      rat hindpaw evoked two types of ventral root discharges that increased during
      stimulation (during-discharges) and after cessation of stimulation (after
      discharges). To explore the involvement of VDCCs in these ventral root
      discharges, several VDCC blockers were applied directly to the surface of the
      spinal cord. Spinalized rats were laminectomized. The fifth lumbar ventral root
      was sectioned and used for multi-unit efferent discharges recording. An agar pool
      was constructed on the first lumbar vertebra for drug application. Ethosuximide
      (a T-type VDCC blocker) had no effect on ventral root discharges. omega-Conotoxin
      GVIA (an N-type VDCC blocker) preferentially suppressed after-discharges. omega
      Agatoxin IVA (a P/Q-type VDCC blocker), diltiazem, and verapamil (L-type VDCC
      blockers) nonselectively depressed both during- and after-discharges. The more
      selective L-type VDCC blocker nicardipine depressed only after-discharges and the
      depression was exhibited when nicardipine was microinjected into the dorsal horn,
      but not into the ventral horn. These findings suggested that N- and L-type VDCCs
      in the dorsal horn were involved in the generation of after-discharges and these
      blockers might be useful for treatment of persistent pain that involves the
      spinal pathway.

PMID- 22641131
TI  - Possible modulation of process extension by N-methyl-D-aspartate receptor
      expressed in osteocytic MLO-Y4 cells.
AB  - In contrast to osteoblasts, little attention has been paid to expression profiles
      of different glutamatergic signaling machineries in osteocytes, which are the
      most abundant cells with a possible role as a mechanical sensor in bone. Here, we
      show that N-methyl-D-aspartate receptor (NMDAR) is expressed by osteocytic cells
      in five-weeks-old mouse tibiae in vivo as well as by osteocytic MLO-Y4 cells in
      vitro. Sustained exposure to the NMDAR antagonist dizocilpine significantly
      increased the number of cells with processes in cultured MLO-Y4 cells. These
      results suggest that NMDAR would be expressed by osteocytes with an unidentified
      role in the process extension.

PMID- 22641130
TI  - Glucocorticoids decrease astrocyte numbers by reducing glucocorticoid receptor
      expression in vitro and in vivo.
AB  - Glucocorticoids are stress hormones released from the adrenal cortex and their
      concentration is controlled by the hypothalamic-pituitary-adrenal axis. In this
      study, we investigated the effect of glucocorticoids on the number of astrocytes
      and glucocorticoid receptor (GR) expression in vitro and in vivo. Proliferation
      of cultured astrocytes was reduced following treatment with corticosterone and
      dexamethasone for 72 h. Corticosterone and dexamethasone also reduced GR
      expression in astrocytes. RU486, a GR antagonist, inhibited the reduction in both
      astrocyte proliferation and GR expression. Furthermore, GR knockdown by siRNA
      inhibited astrocyte proliferation. We also examined the effect of excessive
      glucocorticoid release on GR expression and the number of astrocytes in vivo by
      administering adrenocorticotropic hormone to rats for 14 days. GR expression was
      reduced in the prefrontal cortex and hippocampus and the number of astrocytes was
      reduced in the frontal cortex. Overall, our results suggest that glucocorticoids
      decrease the number of astrocytes by reducing GR expression.

PMID- 22641132
TI  - Pharmacological blockade of IKs destabilizes spiral-wave reentry under beta
      adrenergic stimulation in favor of its early termination.
AB  - We tested a hypothesis that an enhancement of I(Ks) may play a pivotal role in
      ventricular proarrhythmia under high sympathetic activity. A 2-dimensional
      ventricular muscle layer was prepared in rabbit hearts, and action potential
      signals were analyzed by optical mapping. During constant stimulation,
      isoproterenol (ISP, 0.1 uM) significantly shortened action potential duration
      (APD); chromanol 293B (30 uM), a selective I(Ks)-blocker, reversed the APD
      shortening. VTs induced in the presence of ISP lasted longer than in the control,
      and this was reversed by 293B. E-4031 (0.1 uM), a selective I(Kr)-blocker, did
      not cause such reversal. Spiral-wave (SW) reentry with ISP was characterized by
      more stable rotation around a shorter functional block line (FBL) than in the
      control. After application of 293B, SW reentry was destabilized, and rotation
      around a longer FBL with prominent drift reappeared. The APD abbreviation by ISP
      close to the rotation center was more pronounced than in the periphery, leading
      to an opposite APD gradient (center < periphery) compared with controls. This
      effect was also reversed by 293B. In conclusion, beta-adrenergic stimulation
      stabilizes SW reentry most likely though an enhancement of I(Ks). Blockade of
      I(Ks) may be a promising therapeutic modality in prevention of ventricular
      tachyarrhythmias under high sympathetic activity.

PMID- 22641135
TI  - Rheumatoid arthritis: Evidence-based rather than habit-based treatment options.

PMID- 22641137
TI  - Crystal arthritis: Canakinumab relieves gout flares when treatment options are
      limited.

PMID- 22641139
TI  - Osteoarthritis: Control of human cartilage hypertrophic differentiation.

PMID- 22641138
TI  - Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis.
AB  - During osteoarthritis (OA), angiogenesis is increased in the synovium,
      osteophytes and menisci and leads to ossification in osteophytes and the deep
      layers of articular cartilage. Angiogenic and antiangiogenic factors might both
      be upregulated in the osteoarthritic joint; however, vascular growth
      predominates, and the articular cartilage loses its resistance to
      vascularization. In addition, blood vessel growth is increased at--and disrupts-
      the osteochondral junction. Angiogenesis in this location is dependent on the
      creation of channels from subchondral bone spaces into noncalcified articular
      cartilage. Inflammation drives synovial angiogenesis through macrophage
      activation. Blood vessel and nerve growth are linked by common pathways that
      involve the release of proangiogenic factors, such as vascular endothelial growth
      factor, beta-nerve growth factor and neuropeptides. Proangiogenic factors might
      also stimulate nerve growth, and molecules produced by vascular cells could both
      stimulate and guide nerve growth. As sensory nerves grow along new blood vessels
      in osteoarthritic joints, they eventually penetrate noncalcified articular
      cartilage, osteophytes and the inner regions of menisci. Angiogenesis could,
      therefore, contribute to structural damage and pain in OA and provide potential
      targets for new treatments.

PMID- 22641140
TI  - A series of three-dimensional architectures constructed from lanthanide
      substituted polyoxometalosilicates and lanthanide cations or lanthanide-organic
      complexes as linkers.
AB  - Six 3D architectures based on lanthanide-substituted polyoxometalosilicates,
      KLn[(H(2)O)(6)Ln](2)[(H(2)O)(4)LnSiW(11)O(39)](2).nH(2)O (Ln = La 1, n = 42; Ce
      2, n = 40),
      H[(H(2)O)(6)Nd](2)[(H(2)O)(7)Nd][(H(2)O)(4)NdSiW(11)O(39)][(H(2)O)(3)NdSiW(11)O(3
      )].13H(2)O (3),
      H(2)K(2)[(Hpic)(H(2)O)(5)Ln](2)[(H(2)O)(4)LnSiW(11)O(39)](2).nH(2)O (Ln = La 4, n
      = 18.5; Ce 5, n = 35; Nd 6, n = 36; Hpic = 4-picolinic acid), have been
      synthesized and characterized by elemental analysis, IR and UV-vis spectroscopy,
      TG analysis, powder X-ray diffraction and single crystal X-ray diffraction.
      Compounds 1 and 2 are isostructural, built up of lanthanide-substituted
      polyoxoanions [{(H(2)O)(4)Ln(SiW(11)O(39))}(2)](10-) linked by Ln(3+) cations to
      form a 3D open framework with 1D channels. The polyoxoanion
      [{(H(2)O)(4)Ln(SiW(11)O(39))}(2)](10-) consists of two alpha(1)-type mono-Ln
      substituted Keggin anions. When Nd(3+) ion was used instead of La(3+) or Ce(3+)
      ions, compound 3 with a different structure was obtained, containing two kinds of
      polyoxoanions [{(H(2)O)(4)Nd(SiW(11)O(39))}(2)](10-) and
      [{(H(2)O)(3)Nd(SiW(11)O(39))}(2)](10-) which are connected together by Nd(3+)
      ions to yield a 3D framework. When 4-picolinic acid was added to the reaction
      system of 1-3, isostructural compounds 4-6 were obtained, constructed from the
      polyoxoanions [{(H(2)O)(4)Ln(SiW(11)O(39))}(2)](10-) linked by picolinate
      chelated lanthanide centers to form a 3D channel framework. From a topological
      viewpoint, the 3D nets of 1, 2, 4, 5 and 6 exhibit a (3,6)-connected rutile
      topology, whereas the 3D structure of 3 possesses a rare (3,3,6,10)-connected
      topology. The magnetic properties of 2, 3, 5 and 6 have been studied by measuring
      their magnetic susceptibilities in the temperature range 2-300 K.

PMID- 22641141
TI  - Is Drosera meristocaulis a pygmy sundew? Evidence of a long-distance dispersal
      between Western Australia and northern South America.
AB  - BACKGROUND AND AIMS: South America and Oceania possess numerous floristic
      similarities, often confirmed by morphological and molecular data. The
      carnivorous Drosera meristocaulis (Droseraceae), endemic to the Neblina highlands
      of northern South America, was known to share morphological characters with the
      pygmy sundews of Drosera sect. Bryastrum, which are endemic to Australia and New
      Zealand. The inclusion of D. meristocaulis in a molecular phylogenetic analysis
      may clarify its systematic position and offer an opportunity to investigate
      character evolution in Droseraceae and phylogeographic patterns between South
      America and Oceania. METHODS: Drosera meristocaulis was included in a molecular
      phylogenetic analysis of Droseraceae, using nuclear internal transcribed spacer
      (ITS) and plastid rbcL and rps16 sequence data. Pollen of D. meristocaulis was
      studied using light microscopy and scanning electron microscopy techniques, and
      the karyotype was inferred from root tip meristem. KEY RESULTS: The phylogenetic
      inferences (maximum parsimony, maximum likelihood and Bayesian approaches)
      substantiate with high statistical support the inclusion of sect. Meristocaulis
      and its single species, D. meristocaulis, within the Australian Drosera clade,
      sister to a group comprising species of sect. Bryastrum. A chromosome number of
      2n = approx. 32-36 supports the phylogenetic position within the Australian
      clade. The undivided styles, conspicuous large setuous stipules, a cryptocotylar
      (hypogaeous) germination pattern and pollen tetrads with aperture of intermediate
      type 7-8 are key morphological traits shared between D. meristocaulis and pygmy
      sundews of sect. Bryastrum from Australia and New Zealand. CONCLUSIONS: The
      multidisciplinary approach adopted in this study (using morphological,
      palynological, cytotaxonomic and molecular phylogenetic data) enabled us to
      elucidate the relationships of the thus far unplaced taxon D. meristocaulis. Long
      distance dispersal between southwestern Oceania and northern South America is the
      most likely scenario to explain the phylogeographic pattern revealed.

PMID- 22641142
TI  - Iron spin-reorientation transition in NdFeAsO.
AB  - The low-temperature magnetic structure of NdFeAsO has been revisited using
      neutron powder diffraction and symmetry analysis using the Sarah representational
      analysis program. Four magnetic models with one magnetic variable for each of the
      Nd and Fe sublattices were tested. The best fit was obtained using a model with
      Fe moments pointing along the c-direction, and Nd moments along the a-direction.
      This signals a significant interplay between rare-earth and transition metal
      magnetism, which results in a spin-reorientation of the Fe sublattice upon
      ordering of the Nd moments. All models that fit the data well, including
      collinear models with more than one magnetic variable per sublattice, were found
      to have an Fe moment of 0.5 MU(B) and a Nd moment of 0.9 MU(B), demonstrating
      that the low-temperature Fe moment is not substantially enhanced compared to the
      spin-density wave state.

PMID- 22641143
TI  - Successful inhibitory control over an immediate reward is associated with
      attentional disengagement in visual processing areas.
AB  - We examined the neural basis of the capacity to resist an immediately rewarding
      stimulus in order to obtain a larger delayed reward. This was investigated with a
      Go/No-go task employing No-go targets that provided two types of reward outcomes.
      These were contingent on inhibitory control performance: failure to inhibit
      Reward No-go targets provided a small monetary reward with immediate feedback;
      while successful inhibitory control resulted in larger rewards with delayed
      feedback based on the highest number of consecutive inhibitions. We observed
      faster Go trial responses with maintained levels of inhibition accuracy during
      the Reward No-go condition compared to a neutral No-go condition. Comparisons
      between conditions of BOLD activity showed successful inhibitory control over
      rewarding No-Go targets was associated with hypoactivity in regions previously
      associated with regulating emotion and inhibitory control, including insula and
      right inferior frontal gyrus. In addition, regions previously associated with
      visual processing centers that are modulated as a function of visual attention,
      namely the left fusiform and right superior temporal gyri, were hypoactive. These
      findings suggest a role for attentional disengagement as an aid to withholding
      response over a rewarding stimulus and are consistent with the notion that
      gratification can be delayed by directing attention away from immediate rewards.

PMID- 22641144
TI  - Advances in biological monitoring for occupational and environmental health,
      proceedings of the 8th International Symposium on Biological Monitoring in
      Occupational & Environmental Health (ISBM-2010), organized by the Scientific
      Committee on Occupational Toxicology (SCOT), in collaboration with the Scientific
      Committees on Toxicology of Metals (SCTM) and on Rural Health (SCRH) of the
      International Commission on Occupational Health (ICOH). Preface.

PMID- 22641145
TI  - Mothers' perceptions of the negative impact on TV food ads on children's food
      choices.
AB  - This exploratory study investigates the opinions of mothers who have at least one
      child between the ages of 7 and 12 in terms of the impact of TV food advertising
      on their children. This research also examines whether there is any third person
      effect active in mothers' opinions of TV food advertising aimed at children by
      asking them about both the impact on their own children, and the children of
      strangers. The results reveal that most mothers in the study have generally
      negative attitudes toward TV food advertising aimed at children, but they believe
      that the children of strangers are more negatively impacted by exposure to the
      ads than their own children.

PMID- 22641146
TI  - Assessing binge eating. An analysis of data previously collected in bingeing
      rats.
AB  - As interest in the study of binge eating has increased, several measures of
      bingeing have been developed for use in animal models. Two of the measures that
      have been used to distinguish binge-type from normal intake in animal studies
      are: (1) comparing intake at a given point in time between groups, and (2)
      assessing escalation of intake across time within groups. Here we use both of
      these measures to reanalyze data from 10 previous bingeing experiments conducted
      in our lab. Additionally, the data from two of these studies were then
      restructured in order to evaluate the use of these measures in binge eating prone
      (BEP) and resistant (BER) rats, as described by others. Analyses comparing intake
      at a given point in time indicated bingeing in all 10 studies, while comparisons
      of escalation indicated bingeing in 9 out of 10 studies. The goal of this study
      was to compare and contrast the two measures, identify the strengths and
      weaknesses of each, and determine their appropriateness for a given set of
      potential outcomes. The results indicate that both intake and escalation are
      useful measures. However, their limitations need to be taken into consideration
      when attempting to operationalize binge-type eating in animal models.

PMID- 22641147
TI  - Construal levels of healthy eating. Exploring consumers' interpretation of health
      in the food context.
AB  - Although many studies consider health and food, little is known about consumers'
      actual interpretation of healthy eating. This study aims to explore,
      operationalise, and test consumers' interpretation of healthy eating by using
      insights from construal level theory. In this exploratory research three
      consecutive studies were executed, applying focus group (n=35) and two quasi
      experimental studies with, respectively 97 and 235 respondents. Respondents
      appeared to use different levels for their judgment of food products'
      healthiness. Thinking about healthy eating can take place at a concrete
      representation level (e.g. "an apple contains vitamins"), but also at an abstract
      representation level (e.g. "it depends how much you eat"). The main yield of this
      paper is the coding scheme with exemplary phrasings used by consumers for
      different representations of healthy eating. This study shows that healthy eating
      does not always mean the same for different individuals, it depends at least
      partly on the representation level they are reasoning from. Both in academic
      reasoning and public health interventions health and healthy eating are usually
      discussed as universal and univocal concepts. However, this paper argues that
      healthy eating is not as clear-cut for consumers, and is not understood and
      interpreted identically by everybody. This paper suggests to take this insight
      into account in both future research and in the design of any communication
      message on healthy eating.

PMID- 22641148
TI  - Combined two-photon excitation and d -> f energy-transfer in Ir/lanthanide dyads
      with time-gated selection from a two-component emission spectrum.
AB  - In a pair of Ir/Eu and Ir/Tb dyads, two-photon excitation of the Ir
      phenylpyridine chromophore at 780 nm is followed by partial d -> f energy
      transfer to give a combination of short-lived Ir-based (blue) and long-lived
      lanthanide-based (red or green) emission; these components can be selected
      separately by time-gated detection.

PMID- 22641149
TI  - Rare non-synonymous variations in the transcriptional activation domains of GATA5
      in bicuspid aortic valve disease.
AB  - Bicuspid aortic valve (BAV) is the commonest congenital heart disease and a
      highly heritable trait; however, only the NOTCH1 gene has been linked to limited
      cases of BAV in humans. Recently, the transcription factor GATA5 has been shown
      to have an essential role in aortic valve development, and targeted deletion of
      Gata5 in mice is associated with partially penetrant BAV formation. Here, we
      investigated the relationship between GATA5 gene variants and BAV with its
      associated aortopathy. One hundred unrelated individuals with confirmed BAV were
      prospectively recruited. Following collection of clinical information and DNA
      extraction, the coding regions and splice signal sequences of the GATA5 gene were
      screened for sequence variations. The clinical characteristics of the cohort
      included a male predominance (77%), mean age of diagnosis 29 +/- 22 years,
      associated aortopathy in 59% and positive family history for BAV in 13%. Genetic
      analysis identified the presence of 4 rare non-synonymous variations within the
      GATA5 transcriptional activation domains, namely Gln3Arg, Ser19Trp, Tyr142His and
      Gly166Ser, occurring in one patient each. Gln3Arg and Tyr142His substitutions
      affect highly conserved and functionally relevant residues, and are likely to
      impact on the transcriptional activation of GATA5 target regions. A novel
      Ser19Trp variation was identified at a highly conserved amino acid residue in one
      patient, while the Gly166Ser variant was found in a familial case of BAV and
      associated aortopathy. Rare non-synonymous variations in the functionally
      important GATA5 transcriptional activation domains may be important in the
      pathogenesis of BAV disease in humans.

PMID- 22641150
TI  - Transcriptomic analysis reveals atrial KCNE1 down-regulation following lung
      lobectomy.
AB  - Lone atrial fibrillation (AF) is associated with various ion channel gene
      sequence variants, notably the common S38G loss-of-function polymorphism in the
      KCNE1 K(+) channel ancillary subunit gene. New-onset postoperative AF (POAF)
      generally occurs 48-72 h after major surgery, particularly following procedures
      within the chest, but its molecular bases remain poorly understood. To begin to
      address this gap in knowledge, we analyzed molecular changes in the left atrium
      (LA) in relation to simultaneous changes in hemodynamics, LA effective refractory
      period (ERP), and the capacity to sustain electrically-induced AF following left
      upper lung lobectomy in swine. Relative to control pigs (no previous surgery), 3
      days after lobectomy higher values for mean pulmonary artery pressure (16 +/- 1
      vs 22 +/- 2 mmHg; P=0.045) and pulmonary vascular resistance (273 +/- 47 vs 481
      +/- 63 dyns/cm(5); P=0.025) were evident, whereas other hemodynamic variables
      were unchanged. LA ERP trended toward reduction in lobectomy animals (187 +/- 16
      vs 170 +/- 20 ms, P>0.05). None of the lobectomy pigs developed spontaneous POAF
      as assessed by telemetric ECG. However, all lobectomy pigs, but none of the
      controls, were able to sustain AF induced by a 10s burst of rapid pacing for >=
      30 s (P=0.0079), independent of LA ERP; AF was sustained >= 60s in 3/5
      postoperative pigs versus 0/5 controls and correlated with a shorter ERP overall
      (P=0.023). Transcriptomic analysis of LA tissue revealed 23 up-regulated and 10
      down-regulated transcripts (>= 1.5-fold, P<0.05) in lobectomy pigs. Strikingly,
      of the latter, KCNE1 down-regulation showed the statistically strongest link to
      surgery (2.0-fold, P=0.009), recapitulated at the protein level with Western
      blotting (P=0.039), suggesting KCNE1 down-regulation as a possible common
      mechanistic factor in POAF and lone AF. Of the up-regulated transcripts, while
      Teneurin-2 was the strongest linked (1.5-fold change, P=0.001), DSCR5 showed the
      highest induction (2.7-fold, P=0.02); this and other hits will be targeted in
      future functional studies.

PMID- 22641151
TI  - Expression, and molecular and enzymatic characterization of Cu-containing nitrite
      reductase from a marine ammonia-oxidizing gammaproteobacterium, Nitrosococcus
      oceani.
AB  - Ammonia-oxidizing bacteria (AOB) remove intracellular nitrite to prevent its
      toxicity by a nitrifier denitrification pathway involving two denitrifying
      enzymes, nitrite reductase and nitric oxide reductase. Here, a Cu-containing
      nitrite reductase from Nitrosococcus oceani strain NS58, a gammaproteobacterial
      marine AOB, was expressed in Escherichia coli and purified to homogeneity.
      Sequence homology analysis indicated that the nitrite reductase from N. oceani
      was phylogenetically closer to its counterparts from denitrifying bacteria than
      that of the betaproteobacterium Nitrosomonas europaea. The recombinant enzyme was
      a homotrimer of a 32 kDa subunit molecule. The enzyme was green in the oxidized
      state with absorption peaks at 455 nm and 575 nm. EPR spectroscopy indicated the
      presence of type 2 Cu. Molecular activities and the affinity constant for the
      nitrite were determined to be 1.6*10(3) s(-1) and 52 MUM, respectively.

PMID- 22641152
TI  - Detection of vanA-containing Enterococcus species in faecal microbiota of
      gilthead seabream (Sparus aurata).
AB  - Vancomycin-resistant Enterococcus faecalis, E. faecium and E. durans isolates
      with the genotype vanA were detected in 7 of 118 faecal samples (5.9%) of natural
      gilthead seabream recovered off the coast of Portugal, and one vancomycin
      resistant isolate/sample was further characterized. The genes erm(B), tet(L),
      tet(M), aac(6')-aph(2"), aph(3')-IIIa and/or ant(6)-Ia were identified in most of
      the 7 vancomycin-resistant enterococci. Sequence types ST273, ST313 and ST76 were
      detected in three E. faecium isolates and ST6 in two E. faecalis isolates. VanA
      containing enterococci are suggested to be disseminated in fish in marine
      ecosystems close to areas of human activity.

PMID- 22641153
TI  - Functional levels of floor surface roughness for the prevention of slips and
      falls: clean-and-dry and soapsuds-covered wet surfaces.
AB  - Literature has shown a general trend that slip resistance performance improves
      with floor surface roughness. However, whether slip resistance properties are
      linearly correlated with surface topographies of the floors or what roughness
      levels are required for effective slip resistance performance still remain to be
      answered. This pilot study aimed to investigate slip resistance properties and
      identify functional levels of floor surface roughness for practical design
      applications in reducing the risk of slip and fall incidents. A theory model was
      proposed to characterize functional levels of surface roughness of floor surfaces
      by introducing a new concept of three distinctive zones. A series of dynamic
      friction tests were conducted using 3 shoes and 9 floor specimens under clean-and
      dry as well as soapsuds-covered slippery wet environments. The results showed
      that all the tested floor-shoe combinations provided sufficient slip resistances
      performance under the clean-and-dry condition. A significant effect of floor type
      (surface roughness) on dynamic friction coefficient (DFC) was found in the
      soapsuds-covered wet condition. As compared to the surface roughness effects, the
      shoe-type effects were relatively small. Under the soapsuds-covered wet
      condition, floors with 50 MUm in Ra roughness scale seemed to represent an upper
      bound in the functional range of floor surface roughness for slip resistance
      because further increase of surface roughness provided no additional benefit. A
      lower bound of the functional range for slip resistance under the soapsuds
      covered wet condition was estimated from the requirement of DFC > 0.4 at Ra ? 17
      MUm. Findings from this study may have potential safety implications in the floor
      surface design for reducing slip and fall hazards.

PMID- 22641154
TI  - Diffprot - software for non-parametric statistical analysis of differential
      proteomics data.
AB  - Mass spectrometry-based global proteomics experiments generate large sets of data
      that can be converted into useful information only with an appropriate
      statistical approach. We present Diffprot - a software tool for statistical
      analysis of MS-derived quantitative data. With implemented resampling-based
      statistical test and local variance estimate, Diffprot allows to draw significant
      results from small scale experiments and effectively eliminates false positive
      results. To demonstrate the advantages of this software, we performed two spike
      in tests with complex biological matrices, one label-free and one based on iTRAQ
      quantification; in addition, we performed an iTRAQ experiment on bacterial
      samples. In the spike-in tests, protein ratios were estimated and were in good
      agreement with theoretical values; statistical significance was assigned to
      spiked proteins and single or no false positive results were obtained with
      Diffprot. We compared the performance of Diffprot with other statistical tests -
      widely used t-test and non-parametric Wilcoxon test. In contrast to Diffprot,
      both generated many false positive hits in the spike-in experiment. This proved
      the superiority of the resampling-based method in terms of specificity, making
      Diffprot a rational choice for small scale high-throughput experiments, when the
      need to control the false positive rate is particularly pressing.

PMID- 22641155
TI  - Inclusive sharing of mass spectrometry imaging data requires a converter for all.
AB  - With continued efforts towards a single MSI data format, data conversion routines
      must be made universally available. The benefits of a common imaging format,
      imzML, are slowly becoming more widely appreciated but the format remains to be
      used by only a small proportion of imaging groups. Increased awareness amongst
      researchers and continued support from major MS vendors in providing tools for
      converting proprietary formats into imzML are likely to result in a rapidly
      increasing uptake of the format. It is important that this does not lead to the
      exclusion of researchers using older or unsupported instruments. We describe an
      open source converter, imzMLConverter, to ensure against this. We propose that
      proprietary formats should first be converted to mzML using one of the widely
      available converters, such as msconvert and then use imzMLConverter to convert
      mzML to imzML. This will allow a wider audience to benefit from the imzML format
      immediately.

PMID- 22641156
TI  - Farm animal milk proteomics.
AB  - Milk is one of the most important nutrients for humans during lifetime. Farm
      animal milk in all its products like cheese and other fermentation and
      transformation products is a widespread nutrient for the entire life of humans.
      Proteins are key molecules of the milk functional component repertoire and their
      investigation represents a major challenge. Proteins in milk, such as caseins,
      contribute to the formation of micelles that are different from species to
      species in dimension and casein-type composition; they are an integral part of
      the MFGM (Milk Fat Globule Membrane) that has being exhaustively studied in
      recent years. Milk proteins can act as enzymes or have an antimicrobial activity;
      they could act as hormones and, last but not least, they have a latent
      physiological activity encoded in their primary structure that turns active when
      the protein is cleaved by fermentation or digestion processes. In this review we
      report the last progress in proteomics, peptidomics and bioinformatics. These new
      approaches allow us to better characterize the milk proteome of farm animal
      species, to highlight specific PTMs, the peptidomic profile and even to predict
      the potential nutraceutical properties of the analyzed proteins.

PMID- 22641157
TI  - Observing the invisible through imaging mass spectrometry, a window into the
      metabolic exchange patterns of microbes.
AB  - Many microbes can be cultured as single-species communities. Often, these
      colonies are controlled and maintained via the secretion of metabolites. Such
      metabolites have been an invaluable resource for the discovery of therapeutics
      (e.g. penicillin, taxol, rapamycin, epothilone). In this article, written for a
      special issue on imaging mass spectrometry, we show that MALDI-imaging mass
      spectrometry can be adapted to observe, in a spatial manner, the metabolic
      exchange patterns of a diverse array of microbes, including thermophilic and
      mesophilic fungi, cyanobacteria, marine and terrestrial actinobacteria, and
      pathogenic bacteria. Dependent on media conditions, on average and based on
      manual analysis, we observed 11.3 molecules associated with each microbial IMS
      experiment, which was split nearly 50:50 between secreted and colony-associated
      molecules. The spatial distributions of these metabolic exchange factors are
      related to the biological and ecological functions of the organisms. This work
      establishes that MALDI-based IMS can be used as a general tool to study a diverse
      array of microbes. Furthermore the article forwards the notion of the IMS
      platform as a window to discover previously unreported molecules by monitoring
      the metabolic exchange patterns of organisms when grown on agar substrates.

PMID- 22641158
TI  - Proteomic profiling of ATM kinase proficient and deficient cell lines upon
      blockage of proteasome activity.
AB  - Ataxia Telangiectasia Mutated (ATM) protein kinase is a key effector in the
      modulation of the functionality of some important stress responses, including DNA
      damage and oxidative stress response, and its deficiency is the hallmark of
      Ataxia Telangiectasia (A-T), a rare genetic disorder. ATM modulates the activity
      of hundreds of target proteins, essential for the correct balance between
      proliferation and cell death. The aim of this study is to evaluate the phenotypic
      adaptation at the protein level both in basal condition and in presence of
      proteasome blockage in order to identify the molecules whose level and stability
      are modulated through ATM expression. We pursued a comparative analysis of ATM
      deficient and proficient lymphoblastoid cells by label-free shotgun proteomic
      experiments comparing the panel of proteins differentially expressed. Through a
      non-supervised comparative bioinformatic analysis these data provided an insight
      on the functional role of ATM deficiency in cellular carbohydrate metabolism's
      regulation. This hypothesis has been demonstrated by targeted metabolic
      fingerprint analysis SRM (Selected Reaction Monitoring) on specific thermodynamic
      checkpoints of glycolysis. This article is part of a Special Issue entitled:
      Translational Proteomics.

PMID- 22641160
TI  - Kidney cancer: First in vivo study shows optical imaging can distinguish renal
      cancer from normal tissue.

PMID- 22641159
TI  - Protein phosphorylation patterns in serum from schizophrenia patients and healthy
      controls.
AB  - Most proteomic studies to date have attempted to identify changes in protein
      levels without considering the effects of post-translational modifications (PTM).
      However, characteristic changes of PTM such as phosphorylation could be
      biologically informative, as these can give insights into disease and drug
      mechanisms of action at the functional level. With this in mind, we have
      conducted a comparative proteomic and phosphoproteomic analysis of blood sera
      from 20 antipsychotic-naive schizophrenia patients and 20 matched healthy
      controls. We used immobilised metal ion affinity chromatography (IMAC) for
      enrichment of phosphoproteins combined with label-free liquid chromatography-mass
      spectrometry (LC-MS(E)) for identification and measurement of protein and
      phosphoprotein levels. The LC-MS(E) analysis of both IMAC-fractions resulted in
      identification of 35 proteins with altered levels in schizophrenia. Analysis of
      the enriched fraction resulted in identification of 72 phosphoproteins with
      altered phosphorylation patterns. Of these, 59 showed changes in phosphorylation
      only, with no overall change in protein levels. This study provided evidence that
      schizophrenia patients feature serum abnormalities in phosphorylation of proteins
      involved in acute phase response and coagulation pathways. Further studies of
      such phosphorylation-specific changes could lead to a better understanding of the
      molecular aetiology of schizophrenia, and provide a means of biomarker
      identification for clinical studies. This article is part of a Special Issue
      entitled: Integrated omics.

PMID- 22641161
TI  - Sexual dysfunction: C. histolyticum collagenase effective against Peyronie.

PMID- 22641162
TI  - Prostate cancer: celecoxib trampled in the STAMPEDE trial.

PMID- 22641163
TI  - Prostate cancer: PSA testing in older men--are we following the guidelines?

PMID- 22641165
TI  - Synthesis, characterization, and polarized luminescence properties of
      platinum(II) complexes having a rod-like ligand.
AB  - We have synthesized a series of platinum (Pt) complexes having a rod-like ligand:
      'Pt(F(2)PPy)acac', 'Pt(12F(2)PPy)acac', and 'Pt(12F(2)PPyO4)acac'. The crystal
      form of Pt(12F(2)PPy)acac was successfully determined to be triclinic by single
      crystal X-ray structural analysis. The molecules were parallelly aligned in the
      unit cell. Monomer and excimer emissions of Pt(12F(2)PPy)acac were observed in
      hexane solution, poly(methyl methacrylate) film, and various nematic LCs.
      Homogeneous LC cells with the Pt complex/LC mixtures exhibited polarized optical
      emission resulting from monomer and excimer states. The PL intensity
      perpendicular to the orientation direction was higher than the parallel one in
      the whole wavelength region of the Pt complex and the polarization ratio of the
      excimer was higher than that of the monomer. The polarization ratios of the
      excimers were estimated to be 1.4-2.5 in nematic LC at room temperature, and
      decreased gradually with increasing temperature. The polarization ratios of
      Pt(12F(2)PPyO4)acac were higher than those of Pt(F(2)PPy)acac and
      Pt(12F(2)PPy)acac in all the LCs.

PMID- 22641167
TI  - Thermal activation in atomic friction: revisiting the theoretical analysis.
AB  - The effect of thermal activation on atomic-scale friction is often described in
      the framework of the Prandtl-Tomlinson model. Accurate use of this model relies
      on parameters that describe the shape of the corrugation potential beta and the
      transition attempt frequency f(0). We show that the commonly used form of beta
      for a sinusoidal corrugation potential can lead to underestimation of friction,
      and that the attempt frequency is not, as is usually assumed, a constant value,
      but rather varies as the energy landscape evolves. We partially resolve these
      issues by demonstrating that numerical results can be captured by a model with a
      fitted beta and using harmonic transition state theory to develop a variable form
      of the attempt frequency. We incorporate these developments into a more accurate
      and generally applicable expression relating friction to temperature and
      velocity. Finally, by using a master equation approach, we verify the improved
      analytical model is accurate in its expected regime of validity.

PMID- 22641164
TI  - Cancer immunotherapy: a paradigm shift for prostate cancer treatment.
AB  - Prostate cancer remains a significant health problem for men in the Western
      world. Although treatment modalities are available, these do not confer long-term
      benefit and are accompanied by deleterious side effects. Immunotherapy represents
      a valuable alternative to conventional treatments by inducing tumour-specific
      immune responses that control the growth of cancer cells. Sipuleucel-T is
      approved by the FDA as an immunotherapeutic agent for the treatment of patients
      with asymptomatic or minimally symptomatic castration-resistant prostate cancer
      (CRPC). Although this approval has raised cost-versus-benefit issues, it has
      provided proof of concept for the therapeutic potential of active immunotherapy
      approaches for metastatic CRPC. Numerous clinical studies have demonstrated
      clinical benefit using immunotherapy compared to traditional chemotherapy and
      several active immunotherapy approaches (at various developmental stages)have
      demonstrated the potential to change the face of prostate cancer treatment.

PMID- 22641169
TI  - A ferrocenyl-guanidine derivative as a highly selective electrochemical and
      colorimetric chemosensor molecule for acetate anions.
AB  - A highly preorganized chemosensor molecule 1 based on a ferrocenyl-guanidine
      decorated with a chromogenic aryl azo moiety recognizes the acetate anion in
      acetonitrile solution. At first, receptor 1 underwent two-step oxidation events.
      Initially, oxidation of 1 occurs at the Fe(II) centre (E(p) = 440 mV) to form a
      ferrocenium species, followed by fast electron transfer from the guanidine moiety
      of the receptor to the Fe(III) centre with concomitant generation of an Fe(II)
      species with a radical cation centred at the nitrogen atom. In the second step,
      the radical cation species formed should undergo electrochemical oxidation at
      higher potential (E(p) = 830 mV). This assumption is supported by
      spectroelectrochemical studies. A remarkable cathodic shift (182 mV) of the
      ferrocene/ferrocenium oxidation peak (E(p) = 440 mV) and a progressive red-shift
      (Deltalambda = 30 nm) of the low energy band are observed in its absorption
      spectrum upon complexation of receptor 1 with the acetate anion. This change in
      the absorption spectrum is accompanied by a colour change from yellow to orange,
      which can be used for the "naked-eye" detection of this anion. Its monoprotonated
      form is able to selectively sense the less basic Cl(-), Br(-), NO(3)(-), and
      HSO(4)(-) anions: the oxidation redox peak at E(p) = 865 mV is cathodically
      shifted (107-182 mV).

PMID- 22641170
TI  - Factors associated with serious traffic crashes: a prospective study in southwest
      France.

PMID- 22641171
TI  - The propylene glycol research project to illustrate the feasibility and
      difficulties to study toxicokinetics in neonates.
AB  - This paper aims to describe our propylene glycol (PG) research project to
      illustrate the feasibility and the difficulties encountered to perform excipient
      studies in neonates. PG is frequently co-administered excipient. PG accumulation
      potentially results in hyperosmolarity, lactic acidosis or hepato-renal toxicity
      in adults, reflecting issues related to pharmacokinetics (PKs) and -dynamics
      (PDs). Consequently, similar observations in neonates are urgently needed. Since
      newborns display 'physiological' impaired hepatic and renal elimination capacity,
      description of PG PK in neonates is warranted. The PG PD was assessed based on
      indicators of renal, hepatic and metabolic (in)tolerance earlier reported in
      adults and relating to osmolar changes. Based on the PK and PD data collected in
      neonates, we suggest that there is a lower limit of PG tolerance in neonates. In
      addition to preliminary data on PG disposition and tolerance in neonates, we
      mainly focus on the limitations of the current observations and the difficulties
      encountered during this PG project to further illustrate the specific setting of
      neonatal research.

PMID- 22641172
TI  - Nearly complete rRNA genes from 371 Animalia: updated structure-based alignment
      and detailed phylogenetic analysis.
AB  - This study presents a manually constructed alignment of nearly complete rRNA
      genes from most animal clades (371 taxa from ~33 of the ~36 metazoan phyla),
      expanded from the 197 sequences in a previous study. This thorough, taxon-rich
      alignment, available at http://www.wsu.edu/~jmallatt/research/rRNAalignment.html
      and in the Dryad Repository (doi: http://dx.doi.org/10.5061/dryad.1v62kr3q), is
      based rigidly on the secondary structure of the SSU and LSU rRNA molecules, and
      is annotated in detail, including labeling of the erroneous sequences
      (contaminants). The alignment can be used for future studies of the molecular
      evolution of rRNA. Here, we use it to explore if the larger number of sequences
      produces an improved phylogenetic tree of animal relationships. Disappointingly,
      the resolution did not improve, neither when the standard maximum-likelihood
      method was used, nor with more sophisticated methods that partitioned the rRNA
      into paired and unpaired sites (stem, loop, bulge, junction), or accounted for
      the evolution of the paired sites. For example, no doublet model of paired-site
      substitutions (16-state, 16A and 16B, 7A-F, or 6A-C models) corrected the
      placement of any rogue taxa or increased resolution. The following findings are
      from the simplest, standard, ML analysis. The 371-taxon tree only imperfectly
      supported the bilaterian clades of Lophotrochozoa and Ecdysozoa, and this problem
      remained after 17 taxa with unstably positioned sequences were omitted from the
      analysis. The problem seems to stem from base-compositional heterogeneity across
      taxa and from an overrepresentation of highly divergent sequences among the newly
      added taxa (e.g., sequences from Cephalopoda, Rotifera, Acoela, and Myxozoa). The
      rogue taxa continue to concentrate in two locations in the rRNA tree: near the
      base of Arthropoda and of Bilateria. The approximately uncertain (AU) test
      refuted the monophyly of Mollusca and of Chordata, probably due to long-branch
      attraction of the highly divergent cephalopod and urochordate sequences out of
      those clades. Unlikely to be correct, these refutations show for the first time
      that rRNA phylogeny can support some 'wrong' clades. Along with its weaknesses,
      the rRNA tree has strengths: It recovers many clades that are supported by
      independent evidence (e.g., Metazoa, Bilateria, Hexapoda, Nonoculata,
      Ambulacraria, Syndermata, and Thecostraca with Malacostraca) and shows good
      resolution within certain groups (e.g., in Platyhelminthes, Insecta, Cnidaria).
      As another strength, the newly added rRNA sequences yielded the first rRNA-based
      support for Carnivora and Cetartiodactyla (dolphin+llama) in Mammalia, for basic
      subdivisions of Bryozoa ('Gymnolaemata+Stenolaemata' versus Phylactolaemata), and
      for Oligostraca (ostracods+branchiurans+pentastomids+mystacocarids). Future
      improvement could come from better sequence-evolution models that account for
      base-compositional heterogeneity, and from combining rRNA with protein-coding
      genes in phylogenetic reconstruction.

PMID- 22641173
TI  - A multigene species tree for Western Mediterranean painted frogs (Discoglossus).
AB  - Painted frogs (Discoglossus) are an anuran clade that originated in the Upper
      Miocene. Extant species are morphologically similar and have a circum
      Mediterranean distribution. We assembled a multilocus dataset from seven nuclear
      and four mitochondrial genes for several individuals of all but one of the extant
      species and reconstructed a robust phylogeny by applying a coalescent-based
      species-tree method and a concatenation approach, both of which gave congruent
      results. The earliest phylogenetic split within Discoglossus separates D.
      montalentii from a clade comprising all other species. Discoglossus montalentii
      is monophyletic for haplotype variation at all loci and has distinct
      morphological, bioacoustic and karyotypic characters. We find moderate support
      for a sister-group relationship between the Iberian taxa and the Moroccan D.
      scovazzi, and high support for a D. pictus -D. sardus clade distributed around
      the Tyrrhenian basin. Topological discordance among gene trees during the
      speciation of D. galganoi, D. scovazzi, D. pictus and D. sardus is interpreted as
      the consequence of nearly simultaneous, vicariant diversification. The timing of
      these events is unclear, but possibly coincided with the final geotectonic
      rearrangement of the Western Mediterranean in the Middle Miocene or later during
      the Messinian salinity crisis. The Iberian taxa D. galganoi galganoi and D. g.
      jeanneae are reciprocally monophyletic in mitochondrial DNA but not in nuclear
      gene trees, and are therefore treated as subspecies of D. galganoi.

PMID- 22641174
TI  - 1,3,5-Triaryl 2-pyridylidene: base-promoted generation and complexation.
AB  - We herein report a base-promoted generation of sterically hindered 1,3,5-triaryl
      2-pyridylidene from the corresponding pyridinium salt. The thus-generated 2
      pyridylidene was trapped by S(8) and Me(2)SAuCl to form 2-pyridinethione and a 2
      pyridylidene-gold(I) complex, respectively. Rearrangement of pyridylidene to
      pyrido[1,2-a]indole indicates high reactivity of the carbene center of 2
      pyridylidene.

PMID- 22641175
TI  - UCHL1 acts as a colorectal cancer oncogene via activation of the beta-catenin/TCF
      pathway through its deubiquitinating activity.
AB  - Ubiquitin C-terminal hydrolase-L1 (UCHL1) belongs to the family of
      deubiquitinating enzymes (DUBs), which is involved in the ubiquitin-dependent
      proteolytic system. Previously, we have reported that the upregulation of UCHL1
      is related to lymph node metastasis in colorectal cancer (CRC). However, its
      molecular mechanisms remain elusive. In this study, we transfected pcDNA3.1/UCHL1
      and the pcDNA3.1/UCHL1-C90S mutant into HCT8 cells. The changes in biological
      features in these stable transfectants were examined both in vitro and in vivo.
      Western blot analysis was used to analyze the changes in the beta-catenin/T cell
      factor (TCF) pathway. We demonstrated that UCHL1 re-expression promoted the
      proliferation, migration and metastasis potential of HCT8 cells both in vitro and
      in vivo. We also found that UCHL1 could decelerate beta-catenin degradation
      depending on its deubiquitinating activity. The accumulated beta-catenin
      consequently activated the beta-catenin/TCF pathway and induced the expression of
      cyclin D1 and uPA. These observations imply that UCHL1 may contribute to CRC
      progression by activating the beta-catenin/TCF pathway through its deubi
      quitinating activity.

PMID- 22641176
TI  - Multiplexed bead-based immunoassay of four serum biomarkers for diagnosis of
      ovarian cancer.
AB  - The purpose of the present study was to evaluate multiplex liquid assay-based
      measurement of multiple ovarian cancer-associated biomarkers such as hemoglobin,
      haptoglobin and apolipoprotein E, together with CA125, which has been widely used
      in the diagnosis of ovarian cancer, in order to provide a higher diagnostic
      power. We measured the serum levels of CA125, hemoglobin, haptoglobin and
      apolipoprotein E from the serum of 76 healthy individuals and 69 ovarian cancer
      patients using a multiplex liquid assay system, Luminex 100. The results were
      analyzed according to normal versus ovarian cancer, tumor stages and tumor
      histology. In addition, to validate the use of these biomarkers for the diagnosis
      of ovarian cancer, the sensitivity and specificity of each biomarker was analyzed
      by its receiver operating characteristics (ROC) curve. The serum levels of all
      four biomarkers in ovarian cancer patients were significantly higher than those
      of healthy individuals. When CA125 was combined with the biomarkers, the overall
      sensitivity and specificity were significantly improved in the ROC curve, which
      showed 95 and 75% sensitivity and specificity, respectively. At 95% specificity
      for all stages the sensitivity increased to 75% compared to 41% for CA125 alone.
      For stage I+II increased the sensitivity to 68% from 36% for CA125 alone. For
      stage III+IV the corresponding values were 100 and 95%, respectively. Taken
      together, the new combination of hemoglobin, haptoglobin and apolipoprotein E
      with CA125 significantly improved both the sensitivity and the specificity of
      ovarian cancer diagnosis compared with those of individual biomarkers. These
      findings suggest the benefit of the combination of these markers for the
      diagnosis of ovarian cancer.

PMID- 22641177
TI  - An affective disorder in zebrafish with mutation of the glucocorticoid receptor.
AB  - Upon binding of cortisol, the glucocorticoid receptor (GR) regulates the
      transcription of specific target genes, including those that encode the stress
      hormones corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone.
      Dysregulation of the stress axis is a hallmark of major depression in human
      patients. However, it is still unclear how glucocorticoid signaling is linked to
      affective disorders. We identified an adult-viable zebrafish mutant in which the
      negative feedback on the stress response is disrupted, due to abolition of all
      transcriptional activity of GR. As a consequence, cortisol is elevated, but
      unable to signal through GR. When placed into an unfamiliar aquarium ('novel
      tank'), mutant fish become immobile ('freeze'), show reduced exploratory behavior
      and do not habituate to this stressor upon repeated exposure. Addition of the
      antidepressant fluoxetine to the holding water and social interactions restore
      normal behavior, followed by a delayed correction of cortisol levels. Fluoxetine
      does not affect the overall transcription of CRH, the mineralocorticoid receptor
      (MR), the serotonin transporter (Serta) or GR itself. Fluoxetine, however,
      suppresses the stress-induced upregulation of MR and Serta in both wild-type fish
      and mutants. Our studies show a conserved, protective function of glucocorticoid
      signaling in the regulation of emotional behavior and reveal novel molecular
      aspects of how chronic stress impacts vertebrate brain physiology and behavior.
      Importantly, the zebrafish model opens up the possibility of high-throughput drug
      screens in search of new classes of antidepressants.

PMID- 22641178
TI  - The road not taken: life experiences in monozygotic twin pairs discordant for
      major depression.
AB  - In an effort to understand how environmental experiences contribute to risk for
      major depression (MD), we conducted joint autobiographical interviews with 14
      pairs of monozygotic twins (mean age 51.2) rigorously discordant for a lifetime
      history of MD. Twelve of the pairs could be sorted into four broad categories. In
      two pairs, discordance was associated with a single traumatic event occurring to
      the affected twin. In seven pairs, the well twin had one stable, long-term,
      successful romantic relationship, whereas the affected co-twin had romantic
      reversals one or more of which precipitated depressive episodes. These pairs
      varied in the degree to which the romantic problems seemed to arise from bad luck
      or poor choices. In one pair, occupational difficulties were strongly related to
      discordance in experiences with MD. In two pairs, several mechanisms seemed to be
      at work. Discordance in the quality of intimate love relationships was the most
      common etiological factor revealed by interview in these discordant pairs, with
      single dramatic events and occupational problems being considerably rarer. Even
      in this best of natural experiments, the causal interrelationship between
      personality, environment and depressive episodes was not always clear. Many pairs
      illustrated the protective effects of planfulness and the malignant effect of
      cumulative continuity where early difficulties in relationships shaped the
      subsequent life course. These results speak both to the importance of
      environmental influences on human well-being and psychopathology, and the
      complexity of the causal paths underlying their effects. 

PMID- 22641179
TI  - Genetic evidence for association between NOTCH4 and schizophrenia supported by a
      GWAS follow-up study in a Japanese population.

PMID- 22641181
TI  - A new paradigm emerges from the study of de novo mutations in the context of
      neurodevelopmental disease.
AB  - The study of de novo point mutations (new germline mutations arising from the
      gametes of the parents) remained largely static until the arrival of next
      generation sequencing technologies, which made both whole-exome sequencing (WES)
      and whole-genome sequencing (WGS) feasible in practical terms. Single nucleotide
      polymorphism genotyping arrays have been used to identify de novo copy-number
      variants in a number of common neurodevelopmental conditions such as
      schizophrenia and autism. By contrast, as point mutations and microlesions
      occurring de novo are refractory to analysis by these microarray-based methods,
      little was known about either their frequency or impact upon neurodevelopmental
      disease, until the advent of WES. De novo point mutations have recently been
      implicated in schizophrenia, autism and mental retardation through the WES of
      case-parent trios. Taken together, these findings strengthen the hypothesis that
      the occurrence of de novo mutations could account for the high prevalence of such
      diseases that are associated with a marked reduction in fecundity. De novo point
      mutations are also known to be responsible for many sporadic cases of rare
      dominant mendelian disorders such as Kabuki syndrome, Schinzel-Giedion syndrome
      and Bohring-Opitz syndrome. These disorders share a common feature in that they
      are all characterized by intellectual disability. In summary, recent WES studies
      of neurodevelopmental and neuropsychiatric disease have provided new insights
      into the role of de novo mutations in these disorders. Our knowledge of de novo
      mutations is likely to be further accelerated by WGS. However, the collection of
      case-parent trios will be a prerequisite for such studies. This review aims to
      discuss recent developments in the study of de novo mutations made possible by
      technological advances in DNA sequencing.

PMID- 22641180
TI  - A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and
      antidepressant-like activity, improve cognition and control body weight.
AB  - Schizophrenia is a chronic, severe and highly complex mental illness. Current
      treatments manage the positive symptoms, yet have minimal effects on the negative
      and cognitive symptoms, two prominent features of the disease with critical
      impact on the long-term morbidity. In addition, antipsychotic treatments trigger
      serious side effects that precipitate treatment discontinuation. Here, we show
      that activation of the trace amine-associated receptor 1 (TAAR1), a modulator of
      monoaminergic neurotransmission, represents a novel therapeutic option. In
      rodents, activation of TAAR1 by two novel and pharmacologically distinct
      compounds, the full agonist RO5256390 and the partial agonist RO5263397, blocks
      psychostimulant-induced hyperactivity and produces a brain activation pattern
      reminiscent of the antipsychotic drug olanzapine, suggesting antipsychotic-like
      properties. TAAR1 agonists do not induce catalepsy or weight gain; RO5263397 even
      reduced haloperidol-induced catalepsy and prevented olanzapine from increasing
      body weight and fat accumulation. Finally, TAAR1 activation promotes vigilance in
      rats and shows pro-cognitive and antidepressant-like properties in rodent and
      primate models. These data suggest that TAAR1 agonists may provide a novel and
      differentiated treatment of schizophrenia as compared with current medication
      standards: TAAR1 agonists may improve not only the positive symptoms but also the
      negative symptoms and cognitive deficits, without causing adverse effects such as
      motor impairments or weight gain.

PMID- 22641182
TI  - Hydroxychloroquine reduces low-density lipoprotein cholesterol levels in systemic
      lupus erythematosus: a longitudinal evaluation of the lipid-lowering effect.
AB  - The influence of antimalarials on lipids in systemic lupus erythematosus (SLE)
      has been identified in several studies but not in many prospective cohorts. The
      aim of this study was to longitudinally determine the effect of antimalarials on
      the lipoprotein profile in SLE. PATIENTS AND METHODS: Fasting total cholesterol
      (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density
      lipoprotein cholesterol (LDL) plasma levels were determined at entry and after 3
      months of hydroxychloroquine (HCQ) treatment in a longitudinal evaluation of 24
      patients with SLE. RESULTS: a significant decrease in TC (198 +/- 33.7 vs. 183 +/
      30.3 mg/dl, p = 0.023) and LDL levels (117 +/- 31.3 vs. 101 +/- 26.2 mg/dl, p =
      0.023) were detected after the 3 months of HCQ therapy. The reduction of 7.6% in
      TC (p = 0.055) and 13.7% in LDL levels (p = 0.036) determined a significant
      decrease in the frequency of dyslipidemia (26% vs. 12.5%, p = 0.013) after HCQ
      therapy. CONCLUSION: This longitudinal study demonstrated the beneficial effect
      of antimalarials on lipids in SLE since this therapy induced a reduction of
      atherogenic lipoproteins.

PMID- 22641183
TI  - Pigment epithelium-derived factor, insulin sensitivity, and adiposity in
      polycystic ovary syndrome: impact of exercise training.
AB  - Pigment epithelium-derived factor (PEDF) is upregulated in obese rodents and is
      involved in the development of insulin resistance (IR). We aim to explore the
      relationships between PEDF, adiposity, insulin sensitivity, and cardiovascular
      risk factors in obese women with polycystic ovary syndrome (PCOS) and weight
      matched controls and to examine the impact of endurance exercise training on
      PEDF. This prospective cohort intervention study was based at a tertiary medical
      center. Twenty obese PCOS women and 14 non-PCOS weight-matched women were studied
      at baseline. PEDF, cardiometabolic markers, detailed body composition, and
      euglycemic-hyperinsulinemic clamps were performed and measures were repeated in
      10 PCOS and 8 non-PCOS women following 12 weeks of intensified aerobic exercise.
      Mean glucose infusion rate (GIR) was 31.7% lower (P = 0.02) in PCOS compared to
      controls (175.6 +/- 96.3 and 257.2 +/- 64.3 mg.m(-2).min(-1)) at baseline, yet
      both PEDF and BMI were similar between groups. PEDF negatively correlated to GIR
      (r = -0.41, P = 0.03) and high-density lipoprotein (HDL) (r = -0.46, P = 0.01),
      and positively to cardiovascular risk factors, systolic (r = 0.41, P = 0.02) and
      diastolic blood pressure (r = 0.47, P = 0.01) and triglycerides (r = 0.49, P =
      0.004). The correlation with GIR was not significant after adjusting for fat mass
      (P = 0.07). Exercise training maintained BMI and increased GIR in both groups;
      however, plasma PEDF was unchanged. In summary, PEDF is not elevated in PCOS, is
      not associated with IR when adjusted for fat mass, and is not reduced by
      endurance exercise training despite improved insulin sensitivity. PEDF was
      associated with cardiovascular risk factors, suggesting PEDF may be a marker of
      cardiovascular risk status.

PMID- 22641184
TI  - Stereotactic radiosurgery for glioblastoma--time to revisit this approach.

PMID- 22641185
TI  - Defining the limits of the occipital transtentorial keyhole approach.

PMID- 22641186
TI  - Bone morphogenic protein use in the "off-label" setting: is it appropriate?

PMID- 22641187
TI  - Screws, facets, and atlantoaxial instability.

PMID- 22641188
TI  - Synthesis of anisotropic PbS nanoparticles using heterocyclic dithiocarbamate
      complexes.
AB  - We report the synthesis of lead piperidine and lead tetrahydroquinoline
      dithiocarbamate (DTC) complexes and their use as single source precursors for the
      preparation of anisotropic PbS nanoparticles. The complexes were thermolysed in
      coordinating solvents such hexadecylamime (HDA), tri-n-octylphosphine oxide
      (TOPO), oleylamine (OA) and decylamine (DA) at various reaction temperatures. The
      variation of the reaction conditions and precursors produced PbS particles with
      shapes ranging from spheres to cubes and rods. The size of the particles is
      generally larger than those synthesized by conventional precursor routes. The
      electron microscopy and X-ray diffraction data confirm the particles to be very
      crystalline with the dominant cubic rock salt phase present in all samples.

PMID- 22641189
TI  - A novel microfluidics-based method for probing weak protein-protein interactions.
AB  - We report the use of a novel microfluidics-based method to detect weak protein
      protein interactions between membrane proteins. The tight junction protein,
      claudin-2, synthesised in vitro using a cell-free expression system in the
      presence of polymer vesicles as membrane scaffolds, was used as a model membrane
      protein. Individual claudin-2 molecules interact weakly, although the cumulative
      effect of these interactions is significant. This effect results in a transient
      decrease of average vesicle dispersivity and reduction in transport speed of
      claudin-2-functionalised vesicles. Polymer vesicles functionalised with claudin-2
      were perfused through a microfluidic channel and the time taken to traverse a
      defined distance within the channel was measured. Functionalised vesicles took
      1.19 to 1.69 times longer to traverse this distance than unfunctionalised ones.
      Coating the channel walls with protein A and incubating the vesicles with anti
      claudin-2 antibodies prior to perfusion resulted in the functionalised vesicles
      taking 1.75 to 2.5 times longer to traverse this distance compared to the
      controls. The data show that our system is able to detect weak as well as strong
      protein-protein interactions. This system offers researchers a portable, easily
      operated and customizable platform for the study of weak protein-protein
      interactions, particularly between membrane proteins.

PMID- 22641191
TI  - An active loudness model suggesting tinnitus as increased central noise and
      hyperacusis as increased nonlinear gain.
AB  - The present study uses a systems engineering approach to delineate the
      relationship between tinnitus and hyperacusis as a result of either hearing loss
      in the ear or an imbalanced state in the brain. Specifically examined is the
      input-output function, or loudness growth as a function of intensity in both
      normal and pathological conditions. Tinnitus reduces the output dynamic range by
      raising the floor, while hyperacusis reduces the input dynamic range by lowering
      the ceiling or sound tolerance level. Tinnitus does not necessarily steepen the
      loudness growth function but hyperacusis always does. An active loudness model
      that consists of an expansion stage following a compression stage can account for
      these key properties in tinnitus and hyperacusis loudness functions. The active
      loudness model suggests that tinnitus is a result of increased central noise,
      while hyperacusis is due to increased nonlinear gain. The active loudness model
      also generates specific predictions on loudness growth in tinnitus, hyperacusis,
      hearing loss or any combinations of the three conditions. These predictions need
      to be verified by experimental data and have explicit implications for treatment
      of tinnitus and hyperacusis.

PMID- 22641193
TI  - Safety against cervical precancer and cancer following negative human
      papillomavirus and Papanicolaou test results in human immunodeficiency virus
      infected women.

PMID- 22641192
TI  - Mechanisms underlying azimuth selectivity in the auditory cortex of the pallid
      bat.
AB  - This study focused on mechanisms underlying azimuth selectivity in the primary
      auditory cortex (A1) of pallid bats. The pallid bat listens to prey-generated
      noise (5-35 kHz) to localize and hunt terrestrial prey. The region of A1 tuned
      between 5 and 35 kHz consists of two clusters of neurons distinguished by
      interaural intensity difference (IID) selectivity: binaurally inhibited (EI) and
      peaked. The first aim of this study was to use sequential dichotic/free-field
      stimulation to test the hypothesis that IID is the primary cue underlying azimuth
      selectivity in neurons tuned in the prey-generated noise frequency band. IID
      selectivity and ear directionality at the neuron's characteristic frequency (CF)
      were used to predict azimuth selectivity functions. The predicted azimuth
      selectivity was compared with the actual azimuth selectivity from the same
      neurons. Prediction accuracy was similarly high for EI neurons and peaked neurons
      with low CF, whereas predictions were increasingly inaccurate with increasing CF
      among the peaked neurons. The second aim of this study was to compare azimuth
      selectivity obtained with noise and CF tones to determine the extent to which
      stimulus bandwidth influences azimuth selectivity in neurons with different
      binaural properties. The azimuth selectivity functions were similar for the two
      stimuli in the majority of EI neurons. A greater percentage of peaked neurons
      showed differences in their azimuth selectivity for noise and tones. This
      included neurons with multiple peaks when tested with tones and a single peak
      when tested with noise. Taken together, data from the two aims suggest that
      azimuth tuning of EI neurons is primarily dictated by IID sensitivity at CF.
      Peaked neurons, particularly those with high CF, may integrate IID sensitivity
      across frequency to generate azimuth selectivity for broadband sound. The data
      are consistent with those found in cat and ferret A1 in that binaurally
      facilitated neurons depend to a greater extent (compared to EI neurons) on
      spectral integration of binaural properties to generate azimuth selectivity for
      broadband stimuli.

PMID- 22641194
TI  - Characterization of sarcoma-like cells derived from endarterectomized tissues
      from patients with CTEPH and establishment of a mouse model of pulmonary artery
      intimal sarcoma.
AB  - In general, intravascular thrombus formation in the pulmonary arteries is
      considered to be the most common cause of chronic thromboembolic pulmonary
      hypertension (CTEPH). The current mainstay of therapy for patients with CTEPH is
      pulmonary endarterectomy (PEA). Recently, the existence of myofibroblast-like
      cells in endarterectomized tissues has been demonstrated. At the 2nd passage of
      these myofibroblast-like cells, a pleomorphic cell type was isolated. Pulmonary
      intimal sarcoma is a very uncommon neoplastic tumor thought to originate from
      subendothelial-mesenchymal cells of the pulmonary vascular wall. Because these
      pleomorphic cells were isolated from the pulmonary vascular beds, it is believed
      that the analysis of these cells may contribute to the understanding of pulmonary
      intimal sarcoma. We isolated cells from the endarterectomized tissue from
      patients with CTEPH and identified one type as sarcoma-like cells (SCLs). The
      SCLs were characterized as hyperproliferative, anchorage-independent, invasive
      and serum-independent. Moreover, C.B-17/lcr-scid/scidJcl mice injected
      subcutaneously with SCLs developed solid, undifferentiated tumors at the site of
      injection, and those injected intravenously with SCLs via the tail vein developed
      tumors which grew along the intimal surface of the pulmonary vessels, thus,
      demonstrating the high tumorigenic potential of these cells. The behavior of SCLs
      indicated that these cells may have a vascular cell-like potential which can
      affiliate them with the intimal surface of the pulmonary artery, and which may be
      shared with pulmonary intimal sarcoma. A further investigation of this mouse
      model with SCLs may elucidate the mechanism(s) underlying the development of
      pulmonary intimal sarcoma.

PMID- 22641197
TI  - Notch inhibition suppresses nasopharyngeal carcinoma by depleting cancer stem
      like side population cells.
AB  - The cancer stem cell (CSC) is responsible for the initiation, proliferation and
      radiation resistance. Side population (SP) cells are a rare subset of cells
      enriched with CSCs. The targeting of key signaling pathways that are active in
      CSCs is a therapeutic approach to treating cancer. Notch signaling is important
      for the self-renewal and maintenance of stem cells. Our previous studies
      demonstrated that downregulation of Notch signaling could enhance
      radiosensitivity of nasopharyngeal carcinoma (NPC) cells. In this study, we found
      that Notch signaling was highly activated in SP cells compared with that of non
      SP (NSP) cells of NPC. Therefore, Notch inhibition could reduce the proportion of
      SP cells. As SP cells decreased, proliferation, anti-apoptosis and tumorigenesis
      were also decreased. This study shows that Notch inhibition may be a promising
      clinical approach in CSC-targeting therapy for NPC.

PMID- 22641195
TI  - Insulin analogs for the treatment of diabetes mellitus: therapeutic applications
      of protein engineering.
AB  - The engineering of insulin analogs represents a triumph of structure-based
      protein design. A framework has been provided by structures of insulin hexamers.
      Containing a zinc-coordinated trimer of dimers, such structures represent a
      storage form of the active insulin monomer. Initial studies focused on
      destabilization of subunit interfaces. Because disassembly facilitates capillary
      absorption, such targeted destabilization enabled development of rapid-acting
      insulin analogs. Converse efforts were undertaken to stabilize the insulin
      hexamer and promote higher-order self-assembly within the subcutaneous depot
      toward the goal of enhanced basal glycemic control with reduced risk of
      hypoglycemia. Current products either operate through isoelectric precipitation
      (insulin glargine, the active component of Lantus((r)); Sanofi-Aventis) or employ
      an albumin-binding acyl tether (insulin detemir, the active component of
      Levemir((r)); Novo-Nordisk). To further improve pharmacokinetic properties,
      modified approaches are presently under investigation. Novel strategies have
      recently been proposed based on subcutaneous supramolecular assembly coupled to
      (a) large-scale allosteric reorganization of the insulin hexamer (the TR
      transition), (b) pH-dependent binding of zinc ions to engineered His-X(3)-His
      sites at hexamer surfaces, or (c) the long-range vision of glucose-responsive
      polymers for regulated hormone release. Such designs share with wild-type insulin
      and current insulin products a susceptibility to degradation above room
      temperature, and so their delivery, storage, and use require the infrastructure
      of an affluent society. Given the global dimensions of the therapeutic supply
      chain, we envisage that concurrent engineering of ultra-stable protein analog
      formulations would benefit underprivileged patients in the developing world.

PMID- 22641196
TI  - HHV-6 reactivation and associated sequelae after hematopoietic cell
      transplantation.
AB  - Human herpesvirus 6 (HHV-6) reactivation has been associated with acute graft
      versus-host-disease (aGVHD), cytomegalovirus reactivation, and mortality after
      allogeneic hematopoietic cell transplantation (HCT), but previous studies have
      yielded inconsistent results. We performed a large prospective study of
      allogeneic HCT recipients in order to more definitively define the relationships
      between HHV-6 and these important outcomes. Plasma specimens were collected
      prospectively from 315 allogeneic HCT recipients and tested for HHV-6 DNA at
      baseline and twice weekly for 12 weeks. Cox proportional hazards models were used
      to evaluate the time-dependent associations between HHV-6 reactivation and the
      targeted outcomes. HHV-6 was detected in 111 of 315 patients (35%) at a median of
      20 days after HCT. HHV-6 reactivation was associated with subsequent
      cytomegalovirus reactivation (adjusted hazard ratio [aHR], 1.9; 95% confidence
      interval [CI], 1.3-2.8; P = .002). High-level HHV-6 (>1,000 HHV-6 DNA copies/mL)
      was associated with subsequent grades II to IV aGVHD (aHR, 2.4; 95% CI, 1.60-3.6;
      P < .001). High-level HHV-6 reactivation was also associated with nonrelapse
      mortality (aHR, 2.7; 95% CI, 1.2-6.3; P = .02). HHV-6 reactivation was
      independently and quantitatively associated with increased risk of subsequent
      cytomegalovirus reactivation, aGVHD, and mortality after HCT. A randomized
      antiviral trial is warranted to establish causality between HHV-6 and these
      endpoints and to determine if reducing HHV-6 reactivation will improve outcome
      after HCT.

PMID- 22641198
TI  - Significant role of the DNA backbone in mediating the transition origin of
      electronic excitations of B-DNA--implication from long range corrected TDDFT and
      quantified NTO analysis.
AB  - We systematically investigate the possible complex transition origin of
      electronic excitations of giant molecular systems by using the recently proposed
      QNTO analysis [J.-H. Li, J.-D. Chai, G. Y. Guo and M. Hayashi, Chem. Phys. Lett.,
      2011, 514, 362.] combined with long-range corrected TDDFT calculations. Thymine
      (Thy) related excitations of a B-DNA biomolecule are then studied as examples,
      where the model systems have been constructed by extracting from the perfect or
      an X-ray crystal (PDB code 3BSE) B-DNA structure with at least one Thy included.
      In the first part, we consider the systems composed of a core molecular segment
      (e.g. Thy, or di-Thy) and a surrounding physical/chemical environment of interest
      (e.g. backbone, adjacent stacking nucleobases) in gas phase and examine how the
      excitation properties of the core vary in response to the environment. We find
      that the orbitals contributed by the DNA backbone and surrounding nucleobases
      often participate in a transition of Thy-related excitations affecting their
      composition, absorption energy, and oscillator strength. A vast number of
      strongly backbone-orbital involved excitations are also found at an absorption
      wavelength below ~180 nm predicted by TD-omegaB97X. In the second part, we take
      into account geometrically induced variation of the excitation properties of
      various B-DNA segments, e.g. di-Thy, dTpdT etc., obtained from different sources
      (ideal and 3BSE). It is found that the transition origin of several Thy-related
      excitations of these segments is sensitive to slight conformational variations,
      suggesting that DNA with thermal motions may from time to time exhibit very
      different photo-induced physical and/or chemical processes.

PMID- 22641199
TI  - Morphology-controllable growth of GdVO4:Eu3+ nano/microstructures for an optimum
      red luminescence.
AB  - Chemically tailoring microstructures for an optimum red luminescence is a subject
      at the forefront of many disciplines, which still remains a challenge due to a
      poor knowledge about the roles of defects in structures. In this work, GdVO(4) 
      :Eu(3+) nano/microstructures of different morphologies, including tomato-like,
      cookie-circle-like, and ellipsoidal-like nanoparticles, and microspheroids were
      synthesized via a simple hydrothermal route using trisodium citrate as a capping
      agent. During the growth processes, the types of vanadyl ions were adjusted by
      varying pH value to control the morphologies and nano/microstructures with the
      help of trisodium citrate. The possible mechanisms for the growth processes into
      diverse morphologies are presented. Further, a systematic study on defect
      characteristics pertinent to these diverse morphologies has been explored to
      achieve an optimum red luminescence. The ability is clearly shown to generate
      different nano/microstructures of diverse morphologies and varied defect
      concentrations, which provides a great opportunity for morphological control in
      tailoring the red luminescence property for many technological applications.

PMID- 22641200
TI  - A FAST ITERATIVE METHOD FOR SOLVING THE EIKONAL EQUATION ON TRIANGULATED
      SURFACES.
AB  - This paper presents an efficient, fine-grained parallel algorithm for solving the
      Eikonal equation on triangular meshes. The Eikonal equation, and the broader
      class of Hamilton-Jacobi equations to which it belongs, have a wide range of
      applications from geometric optics and seismology to biological modeling and
      analysis of geometry and images. The ability to solve such equations accurately
      and efficiently provides new capabilities for exploring and visualizing parameter
      spaces and for solving inverse problems that rely on such equations in the
      forward model. Efficient solvers on state-of-the-art, parallel architectures
      require new algorithms that are not, in many cases, optimal, but are better
      suited to synchronous updates of the solution. In previous work [W. K. Jeong and
      R. T. Whitaker, SIAM J. Sci. Comput., 30 (2008), pp. 2512-2534], the authors
      proposed the fast iterative method (FIM) to efficiently solve the Eikonal
      equation on regular grids. In this paper we extend the fast iterative method to
      solve Eikonal equations efficiently on triangulated domains on the CPU and on
      parallel architectures, including graphics processors. We propose a new local
      update scheme that provides solutions of first-order accuracy for both
      architectures. We also propose a novel triangle-based update scheme and its
      corresponding data structure for efficient irregular data mapping to parallel
      single-instruction multiple-data (SIMD) processors. We provide detailed
      descriptions of the implementations on a single CPU, a multicore CPU with shared
      memory, and SIMD architectures with comparative results against state-of-the-art
      Eikonal solvers.

PMID- 22641201
TI  - The '3Is' of animal experimentation.
AB  - Animal experimentation in scientific research is a good thing: important,
      increasing and often irreplaceable. Careful experimental design and reporting are
      at least as important as attention to welfare in ensuring that the knowledge we
      gain justifies using live animals as experimental tools.

PMID- 22641202
TI  - Traversing the genomic landscape of prostate cancer from diagnosis to death.
AB  - The clinical spectrum of prostate cancer ranges from curable, local disease to
      widely metastatic, lethal cancer. Two new prostate cancer genome studies provide
      the first glimpse at both ends of this spectrum.

PMID- 22641203
TI  - Exploring the variation within.
AB  - We usually think of an individual's cells as sharing the same genome. Challenging
      this notion, two new studies show that somatic mosaicism is common and can be an
      early herald of cancer.

PMID- 22641204
TI  - One gene's shattering effects.
AB  - A new study shows that three independent mutations in the Sh1 gene, which encodes
      a YABBY transcription factor, gave rise to the non-shattering seed phenotype in
      domesticated sorghum. This same gene may have also had a role in the
      domestication of other cereals, including maize and rice.

PMID- 22641210
TI  - The Pediatric Cancer Genome Project.

PMID- 22641216
TI  - Lysyl oxidase enzymatic function increases stiffness to drive colorectal cancer
      progression through FAK.
AB  - The extracellular, matrix-modifying enzyme lysyl oxidase (LOX) has recently been
      linked to colorectal cancer (CRC) progression, in particular to the stages of
      invasion and metastasis. In this report, we use cell lines expressing a
      catalytically inactive mutant form of LOX to show that catalytic activity is
      required for LOX-mediated effects on proliferation and invasion in both in vitro
      and in vivo models of CRC. Furthermore, we use rheology to measure the relative
      stiffness of modified collagen matrices and subcutaneous tumors, and show that
      LOX-induced collagen cross-linking results in stiffening of the matrix both in
      vitro and in vivo. We observe a strong association between matrix stiffness and
      activation of the FAK (focal adhesion kinase)/SRC-signaling pathway, with a
      stiffer environment resulting in increased FAK/SRC phosphorylation and a more
      proliferative and invasive phenotype. We are the first to show a direct
      relationship between LOX enzymatic activity and tissue stiffness, and to
      demonstrate a role for stiffness in driving CRC progression. Our findings provide
      significant evidence to suggest that therapeutic inhibition of LOX activity may
      provide a novel effective treatment option for patients with metastatic CRC.

PMID- 22641215
TI  - Targeting abnormal DNA double-strand break repair in tyrosine kinase inhibitor
      resistant chronic myeloid leukemias.
AB  - Resistance to imatinib (IM) and other tyrosine kinase inhibitors (TKI)s is an
      increasing problem in leukemias caused by expression of BCR-ABL1. As chronic
      myeloid leukemia (CML) cell lines expressing BCR-ABL1 utilize an alternative non
      homologous end-joining pathway (ALT NHEJ) to repair DNA double-strand breaks
      (DSB)s, we asked whether this repair pathway is a novel therapeutic target in TKI
      resistant disease. Notably, the steady state levels of two ALT NHEJ proteins,
      poly-(ADP-ribose) polymerase 1 (PARP1) and DNA ligase IIIalpha, were increased in
      the BCR-ABL1-positive CML cell line K562 and, to a greater extent, in its
      imatinib-resistant (IMR) derivative. Incubation of these cell lines with a
      combination of DNA ligase and PARP inhibitors inhibited ALT NHEJ and selectively
      decreased survival with the effect being greater in the IMR derivative. Similar
      results were obtained with TKI-resistant derivatives of two hematopoietic cell
      lines that had been engineered to stably express BCR-ABL1. Together our results
      show that the sensitivity of cell lines expressing BCR-ABL1 to the combination of
      DNA ligase and PARP inhibitors correlates with the steady state levels of PARP1
      and DNA ligase IIIalpha, and ALT NHEJ activity. Importantly, analysis of clinical
      samples from CML patients confirmed that the expression levels of PARP1 and DNA
      ligase IIIalpha correlated with the sensitivity to the DNA repair inhibitor
      combination. Thus, the expression levels of PARP1 and DNA ligase IIIalpha serve
      as biomarkers to identify a subgroup of CML patients who may be candidates for
      therapies that target the ALT NHEJ pathway when treatment with TKIs has failed.

PMID- 22641217
TI  - AML1-ETO targets and suppresses cathepsin G, a serine protease, which is able to
      degrade AML1-ETO in t(8;21) acute myeloid leukemia.
AB  - Although the significance of cathepsin G (CTSG) in host defense has been
      intensively investigated, little is known about its potential roles in
      granulopoiesis or leukemogenesis. We report here that CTSG is directly targeted
      and suppressed by AML1-ETO in t(8;21) acute myeloid leukemia (AML). Luciferase
      assays demonstrate that the CTSG promoter is strongly transactivated by AML1 and
      the AML1-dependent transactivation is suppressed by AML1-ETO. We also define a
      novel regulatory mechanism by which AML1-ETO-mediated transrepression requires
      both AML1-ETO and AML1 binding at adjacent sites, instead of the replacement of
      AML1 by AML1-ETO, and wild-type AML1 binding is a prerequisite for the repressive
      effect caused by AML1-ETO. Further evidence shows that CTSG, as a hematopoietic
      serine protease, can degrade AML1-ETO both in vitro and in vivo. Restoration of
      CTSG induces partial differentiation, growth inhibition and apoptosis in AML1-ETO
      positive cells. In addition to t(8;21) AML, CTSG downregulation is observed in
      AML patients with other cytogenetic/genetic abnormalities that potentially
      interrupt normal AML1 function, that is, inv(16) and EVI1 overexpression. Thus,
      the targeting and suppression of CTSG by AML1-ETO in t(8;21) AML may provide a
      mechanism for leukemia cells to escape from the intracellular surveillance system
      by preventing degradation of foreign proteins.

PMID- 22641211
TI  - Exome sequencing and the genetic basis of complex traits.

PMID- 22641218
TI  - TGF-beta and NF-kappaB signal pathway cross-talk is mediated through TAK1 and
      SMAD7 in a subset of head and neck cancers.
AB  - Transforming growth factor-beta (TGF-beta) has a dual role in epithelial
      malignancies, including head and neck squamous cell carcinoma (HNSCC).
      Attenuation of canonical TGF-beta signaling enhances de novo tumor development,
      whereas TGF-beta overexpression and signaling paradoxically promotes malignant
      progression. We recently observed that TGF-beta-induced growth arrest response is
      attenuated, in association with aberrant activation of nuclear factor-kappaB (NF
      kappaB), a transcription factor, which promotes malignant progression in HNSCC.
      However, what role cross-talk between components of the TGF-beta and NF-kappaB
      pathways plays in altered activation of these pathways has not been established.
      Here, we show TGF-beta receptor II and TGF-beta-activated kinase 1 (TAK1) are
      predominantly expressed in a subset of HNSCC tumors with nuclear activation of NF
      kappaB family member RELA (p65). Further, TGF-beta1 treatment induced sequential
      phosphorylation of TAK1, IKK, IkappaBalpha and RELA in human HNSCC lines. TAK1
      enhances TGF-beta-induced NF-kappaB activation, as TAK1 siRNA knockdown decreased
      TGF-beta1-induced phosphorylation of IKK, IkappaB and RELA, degradation of
      IkappaBalpha, RELA nuclear translocation and DNA binding, and NF-kappaB-induced
      reporter and target gene transcription. Functionally, TAK1 siRNA inhibited cell
      proliferation, migration and invasion. Celastrol, a TAK1 inhibitor and anti
      inflammatory compound used in traditional Chinese medicine, also decreased TGF
      beta1-induced phosphorylation of TAK1 and RELA, and suppressed basal, TGF-beta1-
      and tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappaB reporter gene
      activity. Celastrol also inhibited cell proliferation, while increasing sub-G0
      DNA fragmentation and Annexin V markers of apoptosis. Furthermore, TGF-beta and
      RELA activation promoted SMAD7 expression. In turn, SMAD7 preferentially
      suppressed TGF-beta-induced SMAD and NF-kappaB reporters when compared with
      constitutive or TNF-alpha-induced NF-kappaB reporter gene activation. Thus, cross
      talk by TGF-beta via TAK1 and NF-kappaB promotes the malignant phenotype of
      HNSCC. Moreover, NF-kappaB may contribute to the downstream attenuation of
      canonical TGF-beta signaling through increased SMAD7 expression. Celastrol
      highlights the therapeutic potential of agents targeting TAK1 as a key node in
      this pro-oncogenic TGF-beta-NF-kappaB signal pathway.

PMID- 22641219
TI  - A dominant-negative N-terminal fragment of HER2 frequently expressed in breast
      cancers.
AB  - The transmembrane tyrosine kinase HER2 (ErbB2, neu) is a prototypical biomarker
      for breast cancers and a therapeutic target. Although anti-HER2 therapies are
      remarkably effective, HER2-positive tumors are heterogeneous and some subtypes do
      not respond or develop resistance to these therapies. Here we show that H2NTF, a
      novel N-terminal fragment of HER2, is expressed at variable levels in 60% of the
      breast cancer samples analyzed. Characterization of H2NTF shows that it is devoid
      of the tyrosine kinase domain but it readily interacts with full-length HER2 and
      other HER receptors. As a consequence, H2NTF acts as a dominant-negative,
      attenuating the signaling triggered by full-length HER receptors. Expression of
      H2NTF results in resistance to the treatment with low concentrations of
      trastuzumab in vitro. However, cells expressing H2NTF and non-expressing cells
      have similar sensitivity to trastuzumab in vivo, indicating that
      H2NTF/trastuzumab complexes trigger antibody-dependent cell-mediated
      cytotoxicity.

PMID- 22641220
TI  - WEE1 accumulation and deregulation of S-phase proteins mediate MLN4924 potent
      inhibitory effect on Ewing sarcoma cells.
AB  - Ewing sarcoma (ES) is an aggressive bone and soft tissue tumor of children and
      young adults in which finding effective new targeted therapies is imperative.
      Here, we report an in-depth preclinical study of the investigational cullin-RING
      ubiquitin ligase (CRL) inhibitor MLN4924 in ES, as we have recently demonstrated
      the implication of a CRL component in the ES pathogenesis. First, our results
      support a high sensitivity of ES cells to MLN4924 growth inhibition both in vitro
      (14 ES cell lines tested, median IC50=81 nM) and in tumor xenografts (tumor
      regression achieved with 60 mg/kg BID, subcutaneously, n=9). Second, we report a
      dual mechanism of action of MLN4924 in ES cells: while a wide range of MLN4924
      concentrations (~30-300 nM) trigger a G2 arrest that can only be rescued by WEE1
      kinase inhibition or depletion, saturating doses of the drug (>300 nM) cause a
      delay in S-phase progression concomitant with unbalanced CDK2-Cyclin E and CDK2
      Cyclin A relative levels (accumulation of the first and depletion of the latter).
      The aberrant presence of CDC6 in the nucleus at late S-phase cell cycle stage
      confirmed the loss of CDK2-Cyclin A-specific functions. Remarkably, other
      mechanisms explored (P27 accumulation and DNA damage signaling pathways) were
      found unable to explain MLN4924 effects, strengthening the specificity of our
      findings and suggesting the absence of functionality of some CRL substrates
      accumulated in response to MLN4924. This study renders a rationale for clinical
      trials and contributes molecular mechanisms for a better understanding of this
      promising antitumoral agent.

PMID- 22641222
TI  - Pulsed electron spin nutation spectroscopy of weakly exchange-coupled biradicals:
      a general theoretical approach and determination of the spin dipolar interaction.
AB  - Weakly exchange-coupled biradicals have attracted much attention in terms of
      their DNP application in NMR spectroscopy for biological systems or the use of
      synthetic electron-spin qubits. Pulse-ESR based electron spin nutation (ESN)
      spectroscopy applied to biradicals is generally treated as transition moment
      spectroscopy from the theoretical side, illustrating that it is a powerful and
      facile tool to determine relatively short distances between weakly exchange
      coupled electron spins. The nutation frequency as a function of the microwave
      irradiation strength omega(1) (angular frequency) for any cases of weakly
      exchange-coupled systems can be classified into three categories; D(12) (spin
      dipolar interaction)-driven, Deltag-driven and omega(1)-driven nutation behaviour
      with the increasing strength of omega(1). For hetero-spin biradicals, Deltag
      effects can be a dominating characteristic in the biradical nutation
      spectroscopy. Two-dimensional pulse-based electron spin nutation (2D-ESN)
      spectroscopy operating at the X-band can afford to determine small values of
      D(12) in weakly exchange-coupled biradicals in rigid glasses. The analytical
      expressions derived here for omega(1)-dependent nutation frequencies are based on
      only four electronic spin states relevant to the biradicals, while real biradical
      systems often have sizable hyperfine interactions. Thus, we have evaluated
      nuclear hyperfine effects on the nutation frequencies to check the validity of
      the present theoretical treatment. The experimental spin dipolar coupling of a
      typical TEMPO-based biradical 1, (2,2,6,6-tetra[((2)H(3))methyl]-[3,3-(2)H(2),4
      (2)H(1),5,5-(2)H(2)]piperidin-N-oxyl-4-yl)(2,2,6,6-tetra[((2)H(3))methyl]-[3,3
      (2)H(2),4-(2)H(1),5,5-(2)H(2),(15)N]piperidin-(15)N-oxyl-4-yl) terephthalate in a
      toluene glass, with a distance of 1.69 nm between the two spin sites is D(12) = 
      32 MHz (the effect of the exchange coupling J(12) is vanishing due to the homo
      spin sites of 1, i.e.Deltag = 0), while 0 < |J(12)|? 1.0 MHz as determined by
      simulating the random-orientation CW ESR spectra of 1. In addition, we have
      carried out Q-band pulsed ELDOR (ELectron-electron DOuble Resonance) experiments
      to confirm whether the obtained values for D(12) and J(12) are accurate. The
      distance is in a fuzzy region for the distance-measurements capability of the
      conventional, powerful ELDOR spectroscopy. The strong and weak points of the ESN
      spectroscopy with a single microwave frequency applicable to weakly exchange
      coupled multi-electron systems are discussed in comparison with conventional
      ELDOR spectroscopy. The theoretical spin dipolar tensor and exchange interaction
      of the TEMPO biradical, as obtained by sophisticated quantum chemical
      calculations, agree with the experimental ones.

PMID- 22641221
TI  - Biomimetic monolayer-protected gold nanoparticles for immunorecognition.
AB  - Gold nanoparticles (AuNPs) protected by self-assembled monolayers (SAMs) are
      capable of presenting precisely engineered surfaces at the nanoscale, allowing
      the mimicry of biomacromolecules on an artificial platform. Here we review the
      generation, characterization, and applications of monolayer-protected AuNPs that
      have been designed for immunorecognition by the integration of an oligopeptide
      epitope into the protecting monolayer. The resulting peptide-AuNP conjugate is an
      effective platform for biomimesis, as demonstrated by multiple studies. Recent
      work is presented and future directions for this field of research are discussed.

PMID- 22641224
TI  - Evaluation of metal-nanowire electrical contacts by measuring contact end
      resistance.
AB  - It is known, but often unappreciated,  that the performance of nanowire (NW)
      based electrical devices can be significantly affected by electrical contacts
      between electrodes and NWs, sometimes to the extent that it is really the
      contacts that determine the performance. To correctly understand and design NW
      device operation, it is thus important to carefully measure the contact
      resistance and evaluate the contact parameters, specific contact resistance and
      transfer length. A four-terminal pattern or a transmission line model (TLM)
      pattern has been widely used to measure contact resistance of NW devices and the
      TLM has been typically used to extract contact parameters of NW devices. However,
      the conventional method assumes that the electrical properties of semiconducting
      NW regions covered by a metal are not changed after electrode formation. In this
      study, we report that the conventional methods for contact evaluation can give
      rise to considerable errors because of an altered property of the NW under the
      electrodes. We demonstrate that more correct contact resistance can be measured
      from the TLM pattern rather than the four-terminal pattern and correct contact
      parameters including the effects of changed NW properties under electrodes can be
      evaluated by using the contact end resistance measurement method.

PMID- 22641226
TI  - An ECSIT-centric view of Alzheimer's disease.

PMID- 22641227
TI  - Combination of the ERK inhibitor AZD6244 and low-dose sorafenib in a xenograft
      model of human renal cell carcinoma.
AB  - Sorafenib, a multikinase inhibitor, is currently used as monotherapy for advanced
      renal cell carcinoma (RCC). However, adverse effects associated with its use have
      been experienced by some patients. In this study, we examined the antitumor and
      antiangiogenic activities of low-dose sorafenib in combination with the MEK
      inhibitor AZD6244 (sorafenib/AZD6244) in a preclinical model of RCC. Primary RCC
      08-0910 and RCC 786-0 cells as well as patient-derived RCC models were used to
      study the antitumor and antiangiogenic activities of sorafenib/AZD6244. Changes
      of biomarkers relevant to angiogenesis and cell cycle were determined by western
      immunoblotting. Microvessel density, apoptosis and cell proliferation were
      analyzed by immunohistochemistry. Treatment of RCC 786-0 cells with
      sorafenib/AZD6244 resulted in G1 cell cycle arrest and blockade of serum-induced
      cell migration. Sorafenib/AZD6244 induced apoptosis in primary RCC 08-0910 cells
      at low concentrations. In vivo addition of AZD6244 to sorafenib significantly
      augmented the antitumor activity of sorafenib and allowed dose reduction of
      sorafenib without compromising its antitumor activity. Sorafenib/AZD6244 potently
      inhibited angiogenesis and phosphorylation of VEGFR-2, PDGFR-beta and ERK,
      p90RSK, p70S6K, cdk-2 and retinoblastoma. Sorafenib/AZD6244 also caused
      upregulation of p27, Bad and Bim but downregulation of survivin and cyclin B1.
      These resulted in a reduction in cellular proliferation and the induction of
      tumor cell apoptosis. Our findings showed that AZD6244 and sorafenib complement
      each other to inhibit tumor growth. This study provides sound evidence for the
      clinical investigation of low-dose sorafenib in combination with AZD6244 in
      patients with advanced RCC.

PMID- 22641228
TI  - A validated prediction tool for initial survivors of in-hospital cardiac arrest.
AB  - BACKGROUND: Accurate estimation of favorable neurological survival after in
      hospital cardiac arrest could provide critical information for physicians,
      patients, and families. METHODS: Within the Get With the Guidelines-Resuscitation
      registry, we identified 42,957 patients from 551 hospitals admitted between
      January 2000 and October 2009 who were successfully resuscitated from an in
      hospital cardiac arrest. A simple prediction tool for favorable neurological
      survival in patients successfully resuscitated from an in-hospital cardiac arrest
      was developed using multivariate logistic regression, with two-thirds of the
      sample randomly selected as the derivation cohort and one-third as the validation
      cohort. Favorable neurological status was defined as the absence of severe
      neurological deficits (cerebral performance category score of <=2). RESULTS:
      Rates of favorable neurological survival were similar in the derivation cohort
      (7052 patients [24.6%]) and validation cohort (3510 patients [24.5%]). Eleven
      variables were associated with favorable neurological survival: younger age,
      initial cardiac arrest rhythm of ventricular fibrillation or pulseless
      ventricular tachycardia with a defibrillation time of 2 minutes or less, baseline
      neurological status without disability, arrest location in a monitored unit,
      shorter duration of resuscitation, and absence of mechanical ventilation, renal
      insufficiency, hepatic insufficiency, sepsis, malignant disease, and hypotension
      prior to the arrest. The model had excellent discrimination (C statistic of 0.80
      for both the derivation and validation cohorts) and calibration. The prediction
      tool demonstrated the ability to identify patients across a wide range of rates
      of favorable neurological survival: patients in the top decile had a 70.7%
      probability of this outcome, whereas patients in the bottom decile had a 2.8%
      probability. CONCLUSIONS: Among successfully resuscitated patients with an in
      hospital cardiac arrest, a simple, bedside prediction tool provides robust
      estimates of the probability of favorable neurological survival. This tool
      permits accurate prognostication after cardiac arrest for physicians, patients,
      and families.

PMID- 22641233
TI  - Primary bone lymphoma involving bilateral tibia.

PMID- 22641235
TI  - Inhibition of Epstein-Barr virus reactivation in nasopharyngeal carcinoma cells
      by dietary sulforaphane.
AB  - Epstein-Barr virus (EBV) has been associated with several human malignancies
      including nasopharyngeal carcinoma (NPC). Reactivation of latent EBV has been
      considered to contribute to the carcinogenesis of NPC. Blocking the EBV lytic
      cycle has been shown effective in the treatment of EBV-associated diseases. We
      have searched for natural dietary compounds inhibiting EBV reactivation in NPC
      cells. Among them, sulforaphane (SFN) was found to be effective in the inhibition
      of EBV reactivation in latent EBV-positive NPC cells, NA and HA. SFN is a histone
      deacetylase (HDAC) inhibitor and has been recognized as an antioxidant and
      antitumor compound for chemoprevention. However, its antiviral effect is less
      well elucidated. In this study, after determination of the cytotoxicity of SFN on
      various epithelial cells, we showed that SFN treatment inhibits EBV reactivation,
      rather than induction, by detection of EBV lytic gene expression in EBV-positive
      NPC cells. We also determined that the number of cells supporting the EBV lytic
      cycle is decreased using immunofluorescence and flow cytometric analysis.
      Moreover, we have found that this inhibitory effect decreases virus production.
      To elucidate the inhibitory mechanism of SFN on the EBV lytic cycle, luciferase
      reporter assays were carried out on the Zta and Rta promoters. The results show
      that SFN inhibits transactivation activity of the EBV immediate-early gene Rta
      but not Zta. Together, our results suggest that SFN has the capability to inhibit
      EBV lytic cycle and the potential to be taken as a dietary compound for
      prevention of EBV reactivation.

PMID- 22641237
TI  - Native-oxide-based selective area growth of InP nanowires via metal-organic
      molecular beam epitaxy mediated by surface diffusion.
AB  - The growth of InP nanowires on an InP(111) B substrate is reported. The substrate
      native oxide was not removed from the surface prior to growth. Nanowires were
      grown at 400  degrees C from gold catalysts in a selective area manner, without
      bulk growth. Unlike SiO(2)-based metal-organic molecular beam epitaxy selective
      area growth, the growth reported here is mediated by surface diffusion with a
      characteristic diffusion length of 4 MUm, about an order of magnitude larger than
      values for diffusion on bare substrates. A pre-growth heating treatment at 450 
      degrees C was found to increase the yield of nanowire nucleation from the gold
      catalysts.

PMID- 22641236
TI  - CD47 expression regulated by the miR-133a tumor suppressor is a novel prognostic
      marker in esophageal squamous cell carcinoma.
AB  - CD47 inhibits phagocytosis and its overexpression is correlated with poor
      prognosis in patients with several types of cancer. It has also been reported
      that CD47 expression in multiple sclerosis is regulated by microRNAs. However,
      the regulatory mechanism of CD47 in cancer tissues has not been yet clarified. Re
      analysis of a public microarray database revealed that miR-133a is downregulated
      in esophageal squamous cell carcinoma (ESCC). Moreover, in silico algorithms
      predicted that miR-133a is a regulator of CD47. The purpose of this study was to
      clarify the clinical significance of CD47 and its regulatory mechanism by miR
      133a in ESCC. Quantitative real-time RT-PCR was used to evaluate CD47 and miR
      133a expression in 102 cases of curative resected ESCC and adjacent non-cancerous
      tissue. The regulation of CD47 by miR-133a was examined with precursor miR-133a
      transfected cells. A mouse xenograft model was used to investigate the ability of
      miR-133a to suppress tumor progression. High expression levels of CD47 were
      associated with lymph node metastasis (P=0.049). Multivariate analysis showed
      that CD47 expression was an independent prognostic factor (P=0.045). miR-133a
      expression was significantly lower in cancer tissues compared to adjacent non
      cancerous tissues (P<0.001). In vitro assays showed that miR-133a is a direct
      regulator of CD47. miR-133a significantly inhibited tumorigenesis and growth in
      vivo. CD47 expression is a novel prognostic marker in ESCC that is directly
      inhibited by the miR-133a tumor suppressor. This correlation could provide new
      insight into the mechanism of cancer progression and a promising candidate for
      target therapy in ESCC.

PMID- 22641238
TI  - Dynamics of fluorescence depolarisation in star-shaped oligofluorene-truxene
      molecules.
AB  - Star-shaped molecules are of growing interest as organic optoelectronic
      materials. Here a detailed study of their photophysics using fluorescence
      depolarisation is reported. Fluorescence depolarisation dynamics are studied in
      branched oligofluorene-truxene molecules with a truxene core and well-defined
      three-fold symmetry, and are compared with linear fluorene oligomers. An initial
      anisotropy value of 0.4 is observed which shows a two-exponential decay with time
      constants of 500 fs and 3-8 ps in addition to a long-lived component. The
      femtosecond component is attributed to exciton localisation on one branch of the
      molecule and its amplitude reduces when the excitation is tuned to the low energy
      tail of the absorption spectrum. The picosecond component shows a weak dependence
      on the excitation wavelength and is similar to the calculated rate of the
      resonant energy transfer of the localised exciton between the branches. These
      assignments are supported by density-functional theory calculations which show a
      disorder-induced splitting of the two degenerate excited states. Exciton
      localisation is much slower than previously reported in other branched molecules
      which suggests that efficient light-harvesting systems can be designed using
      oligofluorenes and truxenes as building blocks.

PMID- 22641240
TI  - A one-pot sequence for the efficient synthesis of highly functionalized
      macrocarbocycles or bridged 2,8-dioxabicyclo[3.2.1]octanes from 1-nitrobicyclic
      compounds.
AB  - The reaction of 1-nitrobicyclo[n.3.1]alkane-(6 + n)ones with sodium borohydride
      followed by acidic workup led to ring opening via a one-pot sequence comprising
      the retro-Dieckmann-type opening of the alpha-nitroketone structural fragment,
      followed by aldehyde reduction and a final Nef reaction, leading to highly
      functionalized 12 to 14-membered carbocyclic ketones bearing three stereocenters,
      which are adjacent in some of the compounds. The reactions starting from 1
      nitrobicyclo[9.3.1]pentadecan-15-ones could be adjusted to give macrocyclic 2,8
      dioxabicyclo[3.2.1]octanes containing an additional bridge by diastereoselective
      formation of a third ring and a fourth stereocenter through acid-promoted
      intramolecular ketal formation. This is a very interesting ring system related to
      the core of the zaragozic acid family of natural products.

PMID- 22641239
TI  - Responder analysis of the effects of denosumab on bone  mineral density in men
      receiving androgen deprivation  therapy for prostate cancer.
AB  - BACKGROUND: Denosumab, a fully human monoclonal antibody against RANK ligand,
      increased bone mineral density (BMD) and reduced fracture risk vs placebo in a
      phase 3 trial in men with prostate cancer on androgen deprivation therapy (ADT).
      The present analysis of this study evaluated BMD changes after 36 months in
      responder subgroups and in individual patients for three key skeletal sites
      (lumbar spine (LS), femoral neck (FN) and total hip (TH)) and the distal radius.
      METHODS: Men with nonmetastatic prostate cancer receiving ADT were treated with
      subcutaneous denosumab 60 mg (n=734) or placebo (n=734) every 6 months for up to
      36 months in a phase 3, randomized, double-blind study. Patients were instructed
      to take supplemental calcium and vitamin D. For this BMD responder analysis, the
      primary outcome measure was the percentage change in BMD from baseline to month
      36 at the LS, FN and TH as measured by dual-energy X-ray absorptiometry. BMD at
      the distal 1/3 radius at 36 months was measured in a substudy of 309 patients.
      RESULTS: At 36 months, significantly more patients in the denosumab arm had
      increases of >3% BMD from baseline at each site studied compared with placebo
      (LS, 78 vs 17%; FN, 48 vs 13%; TH, 48 vs 6%; distal 1/3 radius, 40 vs 7%
      (P<0.0001 for all)). BMD loss at the LS, FN and TH occurred in 1% of denosumab
      treated patients vs 42% of placebo patients, and BMD gain at all three sites
      occurred in 69% of denosumab patients vs 8% of placebo patients. Lower baseline
      BMD was associated with higher-magnitude BMD responses to denosumab at the LS, FN
      and TH. CONCLUSIONS: In men with prostate cancer receiving ADT, significantly
      higher BMD response rates were observed with denosumab vs placebo. Patients with
      lower baseline T-scores benefited the most from denosumab treatment.

PMID- 22641241
TI  - Vibrational spectroscopic study of the minerals cavansite and pentagonite
      Ca(V4+O)Si4O10.4H2O.
AB  - The bright blue minerals cavansite and pentagonite, a calcium vanadium silicate
      Ca(V(4+)O)Si(4)O(10).4H(2)O, have been studied by UV-Visible, Raman and infrared
      spectroscopy. Cavansite shows an open porous structure with very small micron
      sized holes. Strong UV-Visible absorption bands are observed at around 403, 614
      and 789 nm for cavansite and pentagonite. The Raman spectrum of cavansite is
      dominated by an intense band at 981cm(-1) and pentagonite by a band at 971 cm(-1)
      attributed to the stretching vibrations of (SiO(3))(n) units. Cavansite is
      characterised by two intense bands at 574 and 672 cm(-1) whereas pentagonite by a
      single band at 651 cm(-1). The Raman spectrum of cavansite in the hydroxyl
      stretching region shows bands at 3504, 3546, 3577, 3604 and 3654 cm(-1) whereas
      pentagonite is a single band at 3532 cm(-1). These bands are attributed to water
      coordinated to calcium and vanadium. XPS studies show that bond energy of oxygen
      in oxides is 530eV, and in hydroxides ~531.5 eV and for water ~533.5 eV. XPS
      studies show a strong peak at 531.5eV for cavansite, indicating some OH units in
      the structure of cavansite.

PMID- 22641242
TI  - Ab initio study of the solvent H-bonding effect on ESIPT reaction and electronic
      transitions of 3-hydroxychromone derivatives.
AB  - The electronic transitions occurring in 4-(N,N-dimethylamino)-3-hydroxyflavone
      (DMAF) and 2-furanyl-3-hydroxychromone (FHC) were investigated using the TDDFT
      method in aprotic and protic solvents. The solvent effect was incorporated into
      the calculations via the PCM formalism. The H-bonding between solute and protic
      solvent was taken into account by considering a molecular complex between these
      molecules. To examine the effect of the H-bond on the ESIPT reaction, the
      absorption and emission wavelengths as well as the energies of the different
      states that intervene during these electronic transitions were calculated in
      acetonitrile, ethanol and methanol. The calculated positions of the absorption
      and emission wavelengths in various solvents were in excellent agreement with the
      experimental spectra, validating our approach. We found that in DMAF, the
      hydrogen bonding with protic solvents makes the ESIPT reaction energetically
      unfavourable, which explains the absence of the ESIPT tautomer emission in protic
      solvents. In contrast, the excited tautomer state of FHC remains energetically
      favourable in both aprotic and protic solvents. Comparing our calculations with
      the previously reported time-resolved fluorescence data, the ESIPT reaction of
      DMAF in aprotic solvents is reversible because the emitting states are
      energetically close, whereas in FHC, ESIPT is irreversible because the tautomer
      state is below the corresponding normal state. Therefore, the ESIPT reaction in
      DMAF is controlled by the relative energies of the excited states (thermodynamic
      control), while in FHC the ESIPT is controlled probably by the energetic barrier
      (kinetic control).

PMID- 22641243
TI  - Predicting impacts of increased CO2 and climate change on the water cycle and
      water quality in the semiarid James River Basin of the Midwestern USA.
AB  - Emissions of greenhouse gases and aerosols from human activities continue to
      alter the climate and likely will have significant impacts on the terrestrial
      hydrological cycle and water quality, especially in arid and semiarid regions. We
      applied an improved Soil and Water Assessment Tool (SWAT) to evaluate impacts of
      increased atmospheric CO(2) concentration and potential climate change on the
      water cycle and nitrogen loads in the semiarid James River Basin (JRB) in the
      Midwestern United States. We assessed responses of water yield, soil water
      content, groundwater recharge, and nitrate nitrogen (NO(3)-N) load under
      hypothetical climate-sensitivity scenarios in terms of CO(2), precipitation, and
      air temperature. We extended our predictions of the dynamics of these
      hydrological variables into the mid-21st century with downscaled climate
      projections integrated across output from six General Circulation Models. Our
      simulation results compared against the baseline period 1980 to 2009 suggest the
      JRB hydrological system is highly responsive to rising levels of CO(2)
      concentration and potential climate change. Under our scenarios, substantial
      decrease in precipitation and increase in air temperature by the mid-21st century
      could result in significant reduction in water yield, soil water content, and
      groundwater recharge. Our model also estimated decreased NO(3)-N load to streams,
      which could be beneficial, but a concomitant increase in NO(3)-N concentration
      due to a decrease in streamflow likely would degrade stream water and threaten
      aquatic ecosystems. These results highlight possible risks of drought, water
      supply shortage, and water quality degradation in this basin.

PMID- 22641245
TI  - High frequency performance of individual and arrays of single-walled carbon
      nanotubes.
AB  - We have studied the high frequency performance limits  of single-walled carbon
      nanotube (SWNT) transistors in the diffusive transport regime limited by the
      acoustic phonon scattering. The relativistic band structure of single-walled
      carbon nanotubes combined with the acoustic phonon scattering provides an
      analytical model for the charge transport of the radio frequency transistors. We
      were able to obtain the intrinsic high frequency performance such as the cut-off
      frequency and the linearity of the SWNT transistors. We have extended our model
      to include transistors based on arrays of SWNTs. The effect of electrostatic
      screening in a dense array of SWNTs on the cut-off frequency is studied.

PMID- 22641247
TI  - The clinical impact of breast scintigraphy acquired with a breast specific gamma
      camera (BSGC) in the diagnosis of breast cancer: incremental value versus
      mammography.
AB  - We investigated the clinical impact of breast scintigraphy acquired with a breast
      specific gamma-camera (BSGC) in the diagnosis of breast cancer (BC) and assessed
      its incremental value over mammography (Mx). A consecutive series of 467 patients
      underwent BSGC scintigraphy for different indications: suspicious lesions on
      physical examination and/or on US/MRI negative at Mx (BI-RADS 1 or 3),
      characterization of lesions suspicious at Mx (BI-RADS 4), preoperative staging in
      lesions highly suggestive of malignancy at Mx (BI-RADS 5). Definitive
      histopathological findings were obtained in all cases after scintigraphy: 420/467
      patients had BC, while 47/467 patients had benign lesions. The scintigraphic data
      were correlated to Mx BI-RADS category findings and to histology. The incremental
      value of scintigraphy over Mx was calculated. Scintigraphy was true-positive in
      97.1% BC patients, detecting 96.2% of overall tumor foci, including 91.5% of
      carcinomas <=10 mm, and it was true-negative in 85.1% of patients with benign
      lesions. Scintigraphy gave an additional value over Mx in 141/467 cases (30.2%).
      In particular, scintigraphy ascertained BC missed at Mx in 31 patients with BI
      RADS 1 or 3, including 26 patients with heterogeneously/high dense breast (19/26
      with tumors <=10 mm) and detected additional clinically occult ipsilateral or
      controlateral tumor foci (all <10 mm) or the in situ component sited around
      invasive tumors in 77 BC patients with BI-RADS 4 or 5, changing surgical
      management in 18.2% of these cases; moreover, scintigraphy ruled out malignancy
      in 33 patients with BI-RADS 4. BSGC scintigraphy proved a highly sensitive
      diagnostic tool, even in small size carcinoma detection, while maintaining a high
      specificity. The procedure increased both the sensitivity of Mx, especially in
      dense breast and in multifocal/multicentric disease, and the specificity as well
      as it better defined local tumor extension, thus guiding the surgeon to a more
      appropriate surgical treatment.

PMID- 22641246
TI  - Monitoring performance for blood pressure management among patients with diabetes
      mellitus: too much of a good thing?
AB  - BACKGROUND: Performance measures that reward achieving blood pressure (BP)
      thresholds may contribute to overtreatment. We developed a tightly linked
      clinical action measure designed to encourage appropriate medical management and
      a marker of potential overtreatment, designed to monitor overly aggressive
      treatment of hypertension in the face of low diastolic BP. METHODS: We conducted
      a retrospective cohort study in 879 Department of Veterans Affairs (VA) medical
      centers and smaller community-based outpatient clinics. The clinical action
      measure for hypertension was met if the patient had a passing index BP at the
      visit or had an appropriate action. We examined the rate of passing the action
      measure and of potential overtreatment in the Veterans Health Administration
      during 2009-2010. RESULTS: There were 977,282 established VA patients, 18 years
      and older, with diabetes mellitus (DM). A total of 713,790 patients were eligible
      for the action measure; 94% passed the measure (82% because they had a BP <140/90
      mm Hg at the visit and an additional 12% with a BP >=140/90 mm Hg and appropriate
      clinical actions). Facility pass rates varied from 77% to 99% (P < .001). Among
      all patients with DM, 197,291 (20%) had a BP lower than 130/65 mm Hg; of these,
      80 903 (8% of all patients with DM) had potential overtreatment. Facility rates
      of potential overtreatment varied from 3% to 20% (P < .001). Facilities with
      higher rates of meeting the current threshold measure (<140/90 mm Hg) had higher
      rates of potential overtreatment (P < .001). CONCLUSIONS: While 94% of diabetic
      veterans met the action measure, rates of potential overtreatment are currently
      approaching the rate of undertreatment, and high rates of achieving current
      threshold measures are directly associated with overtreatment. Implementing a
      clinical action measure for hypertension management, as the Veterans Health
      Administration is planning to do, may result in more appropriate care and less
      overtreatment.

PMID- 22641248
TI  - Residual limb wounds or ulcers heal in transtibial amputees using an active
      suction socket system. A randomized controlled study.
AB  - BACKGROUND: The factors that determine successful rehabilitation after lower limb
      amputation have been widely investigated in the literature, but little attention
      has been paid to the type of prosthesis and clinical state of the residual limb,
      particularly the presence of open ulcers. AIM: The aim of this study was to
      investigate the effects of a vacuum-assisted socket system (VASS) in a sample of
      trans-tibial amputees with wounds or ulcers on the stump and to evaluate
      prosthesis use as a primary outcome. Secondary outcome measures were mobility
      with the prosthesis, pain associated with prosthesis use, and wound/ulcer
      healing. STUDY DESIGN: Randomized controlled study. SETTING: Inpatient.
      POPULATION: Twenty dysvascular transtibial amputees suffering from ulcers due to
      prosthesis use or delayed wound healing post-amputation were enrolled. METHODS:
      Participants were separated into two groups: the experimental group was trained
      to use a VASS prosthesis in the presence of open ulcers/wounds on the stump; and
      the control group was trained to use a standard suction socket system prosthesis
      following ulcers/wounds healing. RESULTS: At the end of the 12-week
      rehabilitation program, all VASS users were able to walk independently with their
      prosthesis as reflected by a median Locomotor Capability Index (LCI) value of 42,
      whereas only five participants in the control group were able to walk
      independently with a median LCI value of 21. At the two-month follow-up, the
      participants used their VASS prostheses for 62 hours a week (median; range: 0
      91), which was significantly longer than the control group using the standard
      prosthesis for 5 hours per week (range: 0-56, p=0.003). At the six-month follow
      up, the difference between VASS-users (80, range: 0-112 hours a weeks) and
      control-users (59, range: 0-91) was no longer significant (p=0.191). Despite more
      intense use of the prosthesis, pain and wound healing did not significantly
      differ between the two groups. CONCLUSION: These results showed that the VASS
      prosthesis allowed early fitting with prompt ambulation recovery without
      inhibiting wound healing or increasing pain.

PMID- 22641249
TI  - Choosing a scholarly journal during manuscript submission: the way how it rings
      true for physiatrists.
AB  - BACKGROUND: Research and publications are increasing in Physical and
      Rehabilitation Medicine (PRM). Hence, there appears to be a multifaceted and
      challenging turnover in our scientific niche involving authors, editors,
      publishers and readers in a complex interplay. AIM: To explore the manuscript
      submission process from the side of the authors, and to better understand their
      perceptions and preferences. DESIGN: A survey study. SETTING: E-mail and personal
      contact. POPULATION: European researchers working in the field of PRM. METHODS: A
      questionnaire was specifically prepared for this study. The first part included
      questions regarding personal and scientific background; in the second part the
      attendants rated 20 items (with respect to several journal characteristics) on a
      4-point semantic differential scale; and the third part contained two open ended
      questions regarding additional factors that the authors considered during
      submission. RESULTS: Area of interest (mission and contents) of the journal
      within the "Rehabilitation" category, absolute impact factor of the journal,
      match between perceived "quality" of their study and journal impact factor were
      considered to be the three most important factors by the authors. CONCLUSION: In
      a scientific environment where the numbers of research and publication outlets
      alike are growing, it is important to understand how authors choose where to
      publish their papers. CLINICAL REHABILITATION IMPACT: We believe that editors,
      and publishers as well, would take into account our findings to best meet the
      needs of all actors in the competitive marketplace of scholarly publishing in
      PRM.

PMID- 22641250
TI  - Predicting outcome after stroke: the role of basic activities of daily living
      predicting outcome after stroke.
AB  - BACKGROUND: Very few studies have investigated the influence of single activities
      of daily living (ADL) at admission as possible predictors of functional outcome
      after rehabilitation. AIM: The aim of the current study was to investigate
      admission functional status and performance of basic ADLs as assessed by
      Functional Independence Measure (FIM) scale as possible predictors of motor and
      functional outcome after stroke during inpatient rehabilitation. DESIGN: This is
      a prospective and observational study. SETTING: Inpatients of our Department of
      Physical Medicine and Rehabilitation. POPULATION: Two hundred sixty consecutive
      patients with primary diagnosis of stroke were enrolled and 241 patients were
      used in the final analyses. METHODS: Two backward stepwise regression analyses
      were applied to predict outcome. The first backward stepwise regression had age,
      gender, stroke type, stroke-lesion size, aphasia, neglect, onset to admission
      interval, Cumulative Illness Rating Scale, National Institute of Health Stroke
      Scale (NIHSS), Fugl-Meyer Scale, Trunk Control Test, and FIM (total, motor and
      cognitive scores) as independent variables. The second analyses included the
      above variables plus FIM items as an independent variable. The dependent
      variables were the discharge scores and effectiveness in total and motor-FIM, and
      discharge destination. RESULTS: The first multivariate analysis showed that
      admission Fugl-Meyer, neglect, total, motor and cognitive FIM scores were the
      most important predictors of FIM outcomes, while admission NIHSS score was the
      only predictor of discharge destination. Conversely, when admission single FIM
      items were included in the statistical model, admission Fugl-Meyer, neglect,
      grooming, dressing upper body, and social interaction scores were the most
      important predictors of FIM outcomes, while admission memory and bowel control
      scores were the only predictors of discharge destination. CONCLUSION: Our study
      indicates that performances of basic ADLs are important stroke outcome predictors
      and among which social interaction, grooming, upper body dressing, and bowel
      control are the most important. CLINICAL REHABILITATION IMPACT: The results of
      this study suggests that, when designing other studies on stroke outcome
      predictions, researchers should also include tests which assess performances of
      basic ADLs as independent variables, because this may allow identification of new
      prognostic indicators that can be helpful for the physician for managing stroke
      patients at the end of the rehabilitation period.

PMID- 22641251
TI  - Changes in diastolic function after exercise training in patients with and
      without diabetes mellitus after coronary artery bypass surgery. A randomized
      controlled trial.
AB  - BACKGROUND: Left ventricular diastolic dysfunction and diabetes were associated
      with prognosis after coronary artery bypass surgery (CABG). AIM: This study
      investigated whether short-term exercise improves diastolic function in patients
      with and without diabetes mellitus (DM) after CABG and examined the relationship
      of these changes to exercise capacity. DESIGN: RCT SETTING: Outpatient.
      POPULATION: Patients with left ventricular ejection fraction >=50% after CABG
      were included in this study. METHODS: Participants were randomly assigned to a
      control (N.=33) or exercise (N.=28) group. The exercise group participated in
      three-month treadmill exercise training. We evaluated all participants on
      diastolic function, peak oxygen uptake (VO(2peak)), and concomitant stroke
      volume. RESULTS: Exercise significantly enhanced VO(2peak) to a similar extent in
      all patients (P<0.05). Patients with DM improved in arteriovenous oxygen
      difference ([a-v] O(2) diff) after training (p=0.016), whereas those without DM
      improved in deceleration time of early filling (p=0.031) with exercise training.
      The magnitude of improvement in VO(2peak) correlated with the change in (a-v)
      O(2) diff in patients regardless of DM (r=0.442~0.542) and with baseline (a-v)
      O(2) diff only in patients with DM (r=-0.480). CONCLUSION: After CABG, all
      patients showed similar improvements in VO(2peak) with exercise training, mainly
      through increased (a-v) O(2) diff, but those without DM showed greater
      improvements in deceleration time. CLINICAL REHABILITATION IMPACT: Exercise
      training is beneficial for improving exercise capacity associated with
      restorations of peripheral oxygen utilization in both patients with and without
      DM.

PMID- 22641252
TI  - Objectively measured physical activity in patients with end stage knee or hip
      osteoarthritis.
AB  - BACKGROUND: Patients with lower extremity osteoarthritis (OA) have increased all
      cause and disease specific mortality compared to the general population and
      epidemiological data suggests that OA management should include increased
      physical activity. AIM: To measure physical activity assessed as daily energy
      expenditure and accumulated steps day-1 in patients with severe OA of the hip or
      knee and compare with healthy controls. Furthermore, to investigate if gender,
      age, BMI and affected joint influence measures of physical activity. DESIGN:
      Cross sectional study. SETTING: Community. POPULATION: Fifty-one patients (49%
      women, age: 68+/-5 years, BMI: 28.4+/-4.6) with severe knee (N.=25) or hip
      (N.=26) OA scheduled for total joint replacement and 15 healthy population-based
      controls (53 % women, age: 68+/-5 years, BMI: 26.9+/-4.3). METHODS: Subjects wore
      an accelerometer (SenseWearTM Pro2 Armband) on 5 consecutive days. Time on body,
      total energy expenditure, average intensity (METS), time being sedentary, time
      above 3 METS and numbers of steps day(-1) were calculated. RESULTS: Patients had
      similar daily energy expenditure to controls (2632 vs. 2633 calories per day) but
      walked on average 29.3% fewer steps day(-1) (6632 vs. 8576 P=0.033). Gender and
      affected joint (hip or knee) did not influence the results. Age and BMI explained
      15.4%-32.7% of the variation in total energy expenditure, average METS, time
      being sedentary, and steps day(-1). CONCLUSION: The present data indicate a need
      for interventions improving walking ability in patients with severe hip and knee
      OA. This need is independent regarding gender and affected joint but higher for
      older and heavier patients. Simultaneously assessed measures of physical activity
      gave different results, raising concern about validity of physical activity
      measures in patients with lower extremity OA and indicating caution when
      comparing results from studies applying different measures. CLINICAL
      REHABILITATION IMPACT: It is of potential interest for patients and practitioners
      that a relative high physical activity is possible for end-stage OA patients
      since this may reduce the increased all cause and disease specific mortality.

PMID- 22641254
TI  - Association between the functional independence measure following spinal cord
      injury and long-term outcomes.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVES: To estimate the association
      between the Functional Independence Measure (FIM) for spinal cord injury (SCI)
      patients at time of discharge from rehabilitation and long-term resource
      utilization, residential status and employment. The intention was to assess the
      value of FIM for projecting economic burden in SCI. SETTING: Federally designated
      spinal cord injury model system facilities throughout the USA. METHODS: We
      analyzed data from the National Spinal Cord Injury Statistical Center database (n
      = 14 620) (1988-2010), excluding subjects with: age < 6 years, normal motor
      function, death before discharge or etiology from gunshot or penetrating wound (n
      = 11685 retained). We investigated the association between motor FIM at
      rehabilitation discharge and residential status, survival and outcomes at 1, 5,
      10, 15 and 20 years follow-up, including FIM, residential status,
      hospitalizations, days hospitalized in previous year, daily paid and total care
      and paid hours worked. Regression controlled for injury completeness,
      neurological level, demographic characteristics and temporal effects. RESULTS:
      All outcomes were statistically associated with higher FIM scores at discharge.
      Each one-point increment in FIM was associated with improvements in: probability
      of institution care at discharge (-0.34%) and at follow-up (-0.13%), FIM score at
      follow-up (0.76 points), hospitalizations and days hospitalized/year (-0.0044 and
      -0.071, respectively), probability of needing paid assistance (-0.72%) or any
      assistance (-0.85%) and probability of paid work (0.41%). CONCLUSION: The FIM at
      discharge has predictive value for long-term outcomes. Improvement in FIM
      suggests reduced economic burden in SCI patients. SPONSORSHIP: Novartis
      Pharmaceuticals Corporation.

PMID- 22641253
TI  - Emerging biomarkers of prostate cancer (Review).
AB  - Prostate cancer progression involves activation of signaling pathways controlling
      cell proliferation, apoptosis, anoikis, angiogenesis and metastasis. The current
      PSA-based test for the diagnosis of prostate cancer lacks sensitivity and
      specificity, resulting in missed diagnoses and unnecessary biopsies. Intense
      research efforts to identify serum and tissue biomarkers will expand the
      opportunities to understand the functional activation of cancer-related pathways
      and consequently lead to molecular therapeutic targeting towards inhibition of
      tumor growth. Current literature describes multiple biomarkers that indicate the
      properties of prostate cancer including its presence, stage, metastatic potential
      and prognosis. Used singly, assays detecting these biomarkers have their
      respective shortcomings. Several recent studies evaluating the clinical
      utilization of multiple markers show promising results in improving prostate
      cancer profiling. This review discusses the current understanding of biomarker
      signature cluster-based approaches for the diagnosis and therapeutic response of
      prostate cancer derived from panels of biomarker tests that provide a selective
      molecular signature characteristic of the tumor. As these signatures are robustly
      defined and their pathways are exhaustively dissected, prostate cancer can be
      more accurately diagnosed, characterized, staged and targeted with inhibitory
      antitumor agents. The growing promise surrounding the recent evidence in
      identifying and utilizing such biomarker panels, will lead to improvement in
      cancer prognosis and management of the therapeutic response of prostate cancer
      patients.

PMID- 22641255
TI  - A review of preference-based health-related quality of life questionnaires in
      spinal cord injury research.
AB  - STUDY DESIGN: Systematic review. OBJECTIVES: Review the use of generic preference
      based measures of health-related quality of life (HRQoL) within the context of
      spinal cord injury (SCI). METHODS: A systematic search was conducted to identify
      SCI-related publications that contained any of the following preference-based
      HRQoL instruments: 15D, Assessment of Quality of Life (AQoL)-4D, AQoL-6D, EQ-5D,
      EQ-5D-5L, Health Utilities Index (HUI)-2, HUI-3, Quality of Well-Being Scale Self
      Administered (QWB-SA), SF-6D(SF-36) or SF-6D(SF-12). In addition to providing an
      overview of how different preference-based measures have been adopted in SCI
      research to-date, a focus of evaluation was to collate and appraise evidence for
      measurement properties and identify knowledge gaps. RESULTS: Twenty-two articles
      were identified. No studies have used preference-based measures in their
      conventional form, that is, to calculate quality-adjusted life years using
      patient-level data. Eleven papers reported mean utility scores (across six
      different instruments). Directly comparable data exists for only one SCI-specific
      sample, which showed variation across EQ-5D (0.63), HUI-2 (0.81) and HUI-3 (0.68)
      index scores. Indirect comparisons suggested differences between QWB-SA and SF-6D
      index scores within tetraplegic and paraplegic patient groups. Only the QWB-SA
      and SF-6D have undergone (partial) psychometric evaluation, with the respective
      authors concluding that the measures have potential for SCI research.
      CONCLUSIONS: Despite 'cost-effectiveness' being an increasingly important
      consideration for decision makers in all areas of health care, there is a
      distinct lack of conceptual or empirical research regarding the appropriateness
      of alternative preference-based HRQoL measures for SCI populations. Given the
      support for economic evaluation within a cost-utility framework and the paucity
      of psychometric evidence regarding current instruments, further research is
      needed.

PMID- 22641256
TI  - The use of bronchodilators in people with recently acquired tetraplegia: a
      randomised cross-over trial.
AB  - STUDY DESIGN: A within-participant, double-blind, cross-over, randomised control
      trial. OBJECTIVES: To determine the short-term effects of bronchodilator therapy
      on respiratory function in people with recently acquired motor complete
      tetraplegia. SETTING: Hospital, Australia. METHODS: A total of 12 people with
      recently acquired tetraplegia were randomised to receive either a one-off dose of
      a bronchodilator followed by an equivalent dose of a placebo propellant between 1
      day and 1 week later or visa versa. The three outcomes were forced expiratory
      volume in 1 s (FEV1), peak expiratory flow rate (PEF) and forced vital capacity
      (FVC). These were measured while supine by a blinded assessor 10 and 30 min after
      treatment. Data were analysed on 11 participants and reported as percentage of
      predicted. RESULTS: The FEV1, FVC and PEF mean between-group differences (95%
      confidence interval) at 10 min post treatment were 7.3% (2.7-11.9%; P=0.003),
      5.5% (1.6-9.4%; P=0.008) and 20.1% (1.1-40.4%; P=0.039). Similar effects were
      observed at 30 min for FVC and FEV1 but not for PEF. CONCLUSION: Bronchodilator
      therapy has a beneficial effect on FEV1, FVC and PEF in participants with
      recently acquired tetraplegia.

PMID- 22641257
TI  - Nontraumatic spinal epidural hematoma during pregnancy: diagnosis and management
      concerns.
AB  - OBJECTIVE: Nontraumatic spinal epidural hematoma (SEH) during pregnancy is rare.
      Therefore, appropriate management of this occurrence is not well defined. The aim
      of this study was to extensively review the literature on this subject, to
      propose some novel treatment guidelines. METHODS: Electronic databases, manual
      reviews and conference proceedings up to December 2011 were systematically
      reviewed. Articles were deemed eligible for inclusion in this study if they dealt
      with nontraumatic SEH during pregnancy. Search protocols and data were
      independently assessed by two authors. RESULTS: In all, 23 case reports were
      found to be appropriate for review. The mean patient age was 28 years and
      gestational age was 33.2 weeks. Thirteen cases presented with acute interscapular
      pain. The clinical picture consisted of paraplegia, which occurred approximately
      63 h after pain onset. Spinal cord decompression was performed within an average
      time of 20 h after neurological deficit onset. Fifteen patients had cesarean
      deliveries, even when the gestational age was less than 36 weeks. CONCLUSION:
      This review failed to identify articles, other than case reports, which could
      assist in the formation of new guidelines to treat SEH in pregnancy. However, we
      believe that SEH may be managed neurosurgically, without requiring prior,
      premature, cesarean section.

PMID- 22641258
TI  - [Assessment of airway inflammation in chronic obstructive pulmonary disease:
      biomarkers in exhaled breath condensate].
AB  - Airway inflammation plays a central role in the pathophysiology of chronic
      obstructive pulmonary disease. Exposure to cigarette smoke induces the
      recruitment of inflammatory cells in the airways, which in turn produces various
      cytokines, chemokines, proteases and pro-inflammatory mediators leading
      ultimately to increased oxidative stress, a protease/anti-protease imbalance and
      progressive lung tissue injury. Biomarkers may be useful in monitoring airway
      inflammation and oxidative stress, defining different phenotypes of the disease
      and evaluating the response of therapies. Exhaled breath condensate collection is
      a simple and completely non-invasive method of sampling the lower respiratory
      tract in humans. Exhaled breath condensate may be a rich source of pulmonary
      biomarkers including hydrogen peroxide, cytokines, metabolites of the arachidonic
      acid, nitric oxides and the pH. However, the concentration of these biomarkers is
      often very low, which may cause several problems in their detection. The clinical
      applicability of exhaled breath condensate biomarkers cannot be assessed until
      methods of sample collection and analysis have been standardized.

PMID- 22641259
TI  - [Molecular genetic diagnosis of Friedreich's ataxia. Ten years experience based
      on blood sample analysis].
AB  - Mutations of the frataxin gene give the most common underlying genetic background
      of recessively inheritable type ataxias in Europe. In our department, we have
      been establishing the molecular genetic diagnosis of Friedreich's ataxia since
      2001. We analyzed a total of 221 blood samples from the whole country. METHODS:
      After fragment analysis we performed direct exon sequencing. RESULTS: This study
      summarizes the retrospective analysis of these genetic test results. Pathological
      alteration was identified in altogether 26 cases. 2 expanded alleles were found
      in intron 1 in all 26 genetically confirmed patients; which is not more than 12%
      of the total analyzed samples. We did exon sequencing in the case of patients
      having one expanded allele and found no point mutation in any of the cases.
      CONCLUSIONS: In our setting, we could not verify the diagnosis by genetic
      analysis in a remarkable number of patients, which on one hand underlines the
      importance of clinical neurologic and clinical genetic analyses before performing
      tests, and on the other hand, it raises the need to examine the patients for
      other ataxia types.

PMID- 22641260
TI  - [Effectiveness of generic rosuvastatin in patients with ischaemic cerebrovascular
      disease].
AB  - Statin therapy is the cornerstone of anti-atherosclerotic treatment, and it
      considered obligatory in the secondary prevention of atherosclerotic diseases.
      Rosuvastatin is well-known and efficacious lipid-lowering agent. Generic drugs
      are more frequently used instead of its ancestors. Generic rosuvastatin forms
      have been approved recently to the Central European market, but their safety and
      efficacy have not been previously examined in cerebrovascular patient
      populations. PATIENTS AND METHODS: 109 patients with documented ischaemic
      cerebrovascular events were included in our study. 20 mg generic rosuvastatin
      significantly decreased total cholesterol (5.47 vs. 3.88 mmol/l, p<0.01), low
      density lipoprotein (3.16 vs. 1.84 mmol/l, p<0.01) and trigliceride levels (1.77
      vs. 1.33 mmol/l, p<0.05, and there was a non-significant high-density lipoprotein
      increasing tendency (1.27 vs. 1.36 mmol/l, p = 0.08). There was also a
      significant decrease in high-sensitive C-reactive protein levels (3.73 vs. 2.82
      mg/l, p<0.05). Overall, 30% decrease in total cholesterol, 42% decrease in low
      density lipoprotein, 25% decrease in trigliceride and high-sensitive C-reactive
      protein and 9% increase in high-density lipoprotein levels were observed.
      CONCLUSIONS: The generic rosuvastatin studied by the authors proved to be safe
      and efficacious lipid-lowering agent. Based on these short term results, in daily
      practice, generic rosuvastatin treatment seems to be cost-effective for the
      treatment of patients with ischemic cerebrovascular disease.

PMID- 22641261
TI  - [Effect of "Pintes" white wine on metabolic parameters in patients with metabolic
      syndrome].
AB  - Moderate alcohol consumption has been associated with decreased cardiovascular
      mortality in the general population. Relatively few studies have been conducted
      to evaluate the effect of white wine on insulin sensitivity. AIMS: The authors
      studied the impact of moderate Pintes white wine consumption on insulin
      sensitivity and other metabolic parameters. METHODS: The prospective study
      involved 18 patients with metabolic syndrome. The patients consumed Pintes white
      wine for 4 weeks, and parameters were measured before and after consumption.
      RESULTS: The HOMA-IR decreased significantly after white wine consumption (2.28+/
      2.04 vs 1.08+/-0.6; p = 0.002). There were no changes in serum cholesterol, LDL
      cholesterol, triglyceride and fasting plasma glucose levels. CONCLUSION: White
      wine consumption improved insulin sensitivity in patients with metabolic
      syndrome.

PMID- 22641262
TI  - [Bela Koteles, a remarkable sponsor of Hungarian heart surgery].

PMID- 22641263
TI  - [Tibor Valyi-Nagy (1912-1969), professor and researcher of pharmacology, was born
      one hundred years ago].

PMID- 22641264
TI  - [The Bible---with the eyes of the physician V].

PMID- 22641266
TI  - 'Green'-synthesized near-infrared PbS quantum dots with silica-PEG dual-layer
      coating: ultrastable and biocompatible optical probes for in vivo animal imaging.
AB  - In this paper, PbS semiconductor quantum dots (QDs) with near-infrared (NIR)
      photoluminescence were synthesized in oleic acid and paraffin liquid mixture by
      using an easily handled and 'green' approach. Surface functionalization of the
      QDs was accomplished with a silica and polyethylene glycol (PEG) phospholipid
      dual-layer coating and the excellent chemical stability of the nanoparticles is
      demonstrated. We then successfully applied the ultrastable PbS QDs to in vivo
      sentinel lymph node (SLN) mapping of mice. Histological analyses were also
      carried out to ensure that the intravenously injected nanoparticles did not
      produce any toxicity to the organism of mice. These experimental results
      suggested that our ultrastable NIR PbS QDs can serve as biocompatible and
      efficient probes for in vivo optical bioimaging and has great potentials for
      disease diagnosis and clinical therapies in the future.

PMID- 22641267
TI  - Translational and rotational energy content of benzene molecules IR-desorbed from
      an in vacuo liquid surface.
AB  - Benzene molecules were desorbed from an in vacuo aqueous liquid beam by direct
      irradiation of the beam with an IR laser tuned to the 2.85 MUm absorption band of
      water. Spectroscopic interrogation of the desorbed benzene molecules was
      performed via 1 + 1 Resonance-Enhanced Multi-photon Ionisation (REMPI).
      Rotational contour analyses of the 6 vibronic transition of benzene were
      performed to determine the rotational temperature of those molecules ejected
      during the desorption event. At the peak of the desorption plume density, the
      rotational temperatures were found to be up to ~100 K lower than that recorded
      for molecules spontaneously evaporating from the liquid surface. At longer IR-UV
      laser delay times the benzene rotational temperatures are found to return to
      those observed following spontaneous evaporation. No evidence of IR desorbed
      neutral or cationic benzene-containing clusters was observed. However, ionic
      clusters were observed to be formed after REMPI of the benzene monomer. Analysis
      of the benzene intensity and that of post-REMPI formed clusters as a function of
      IR-UV delay shows that number density and local translational temperature vary
      along the desorption plume.

PMID- 22641268
TI  - Synthesis of selective inhibitors against V. cholerae sialidase and human
      cytosolic sialidase NEU2.
AB  - Sialidases or neuraminidases catalyze the hydrolysis of terminal sialic acid
      residues from sialyl oligosaccharides and glycoconjugates. Despite successes in
      developing potent inhibitors specifically against influenza virus neuraminidases,
      the progress in designing and synthesizing selective inhibitors against bacterial
      and human sialidases has been slow. Guided by sialidase substrate specificity
      studies and sialidase crystal structural analysis, a number of 2-deoxy-2,3
      dehydro-N-acetylneuraminic acid (DANA or Neu5Ac2en) analogues with modifications
      at C9 or at both C5 and C9 were synthesized. Inhibition studies of various
      bacterial sialidases and human cytosolic sialidase NEU2 revealed that
      Neu5Gc9N(3)2en and Neu5AcN(3)9N(3)2en are selective inhibitors against V.
      cholerae sialidase and human NEU2, respectively.

PMID- 22641269
TI  - Structural diversity in sodium doped water trimers.
AB  - The structures of sodium doped water trimers are characterized on the basis of
      their infrared action spectra in the OH-stretching region and a global
      optimization approach to identify the lowest energy minima. The most stable
      structure is an open ring with two contacts of terminal water molecules to the Na
      atom. This structure explains the dominating feature in the IR depletion spectrum
      around 3410 cm(-1). Three additional isomer classes were found in an energy
      window of 12 kJ mol(-1) with vertical ionization energies ranging from ~3.83 eV
      to ~4.36 eV. These structures show different hydrogen bonding and sodium
      coordination patterns and are identified by specific spectral features in the IR
      spectra. The significant abundance of closed rings with an external Na atom,
      resembling the undoped water trimer, suggests that for larger clusters the
      picture of the sodium atom being situated on the cluster surface seems adequate.

PMID- 22641271
TI  - How do guidelines impact measures of performance? Can they keep up?

PMID- 22641273
TI  - Use of systemic antifungals in daily clinical practice in the haematology and
      oncology setting: results of a prospective observational analysis.
AB  - PURPOSE: To assess the role of systemic antifungal drugs as well as the frequency
      of potential drug interactions and adverse drug events of commonly used
      antifungals in an unselected haematology/oncology patient cohort. METHODS: A
      prospective analysis was performed in our haematology/oncology department between
      October 2006 and September 2009. Data were obtained from 250 consecutive patients
      who received treatment and/or prophylaxis with fluconazole (n = 191), liposomal
      amphotericin B (n = 105), voriconazole (n = 62), caspofungin (n = 27) and/or
      posaconazole (n = 22). We performed detailed reviews of patient charts and
      laboratory values in close cooperation with treating physicians and nursing staff
      and participated regularly in ward and chart rounds. Potential drug interactions
      were assessed using the electronic database Micromedex(r) 1.0 (Healthcare
      Series). RESULTS: In terms of adverse drug events, caspofungin (56%) and
      voriconazole (58%) revealed a slightly more favourable safety profile than
      liposomal amphotericin B (66%) and posaconazole (64%). We confirmed frequent
      nephrotoxic effects with the use of liposomal amphotericin B (20%). Regarding
      potential drug interactions, 97 (66%) of 147 evaluated patients were exposed to
      at least 1 of 22 different potentially interacting drug combinations involving
      systemic antifungal agents. Cyclosporine was the most prevalent potentially
      interacting drug in our cohort. CONCLUSIONS: Systemic antifungal drugs are widely
      used in the haematology/oncology setting and exhibit numerous potential drug
      interactions and adverse events in cancer patients. Our results highlight the
      challenges related to antifungal drugs and should valuably contribute to a safe
      and efficient application of this increasingly important class of drugs.

PMID- 22641276
TI  - End tidal carbon dioxide levels during the resuscitation of prematurely born
      infants.
AB  - BACKGROUND: Successful resuscitation of prematurely born infants is dependent on
      achieving adequate alveolar ventilation and vasodilation of the pulmonary
      vascular bed. Elevation of end-tidal carbon dioxide (ETCO(2)) levels may indicate
      pulmonary vasodilation. AIMS: This research aims to study the temporal changes in
      ETCO(2) levels and the infant's respiratory efforts during face mask
      resuscitation in the labour suite, and to determine if the infant's first
      inspiratory effort was associated with a rise in the ETCO(2) levels, suggesting
      pulmonary vasodilation had occurred. STUDY DESIGN: This study is an observational
      one. SUBJECTS: The subjects of the study are forty infants with a median
      gestational age of 30 weeks (range 23-34). OUTCOME MEASURES: Inflation pressures,
      expiratory tidal volumes and ETCO(2) levels were measured. RESULTS: The median
      expiratory tidal volume of inflations prior to the onset of the infant's
      respiratory efforts (passive inflations) was lower than that of the inflation
      associated with the first inspiratory effort (active inflation) (1.8 (range 0.1
      7.3) versus 6.3 ml/kg (range 1.9-18.4), p<0.001), as were the median ETCO(2)
      levels (0.3 (range 0.1-2.1) versus 3.4 kPa (0.4-11.5), p<0.001). The median
      expiratory tidal volume (4.5 ml/kg (range 0.5-18.3)) and ETCO(2) level (2.2 kPa
      (range 0.3-9.3)) of the two passive inflations following the first active
      inflation were also higher than the median expiratory tidal volume and ETCO(2)
      levels of the previous passive inflations (p<0.001, p<0.0001 respectively).
      CONCLUSION: These results suggest that during face mask resuscitation, improved
      carbon dioxide elimination, likely due to pulmonary vasodilation, occurred with
      the onset of the infant's respiratory efforts.

PMID- 22641277
TI  - Resistin and leptin in breast milk and infants in early life.
AB  - BACKGROUND: The role of adipokines in early life is considered an emerging topic
      issue in nutritional researches. AIMS: To evaluate serum resistin and leptin
      concentrations and their relations in infants and in breast milk. STUDY DESIGN:
      We enrolled 41 term, AGA, healthy infants, of which 23 exclusively breast-fed
      (BF) and 18 formula-fed (FF), aged less than 6 months. Breast milk (BM) samples
      were collected from 23 breastfeeding mothers of the infants enrolled. Resistin
      concentration in serum and BM was determined by ELISA test (Human-Resistin-ELISA,
      Mediagnost, Reutlingen, Germany). Leptin concentration was determined by
      Radioimmunoassay method (LEP-R40, Mediagnost, Reutlingen, Germany). Infants
      weight, length and body mass index were measured. We used Mann-Whitney test.
      Spearman correlation was applied. Statistical significance was set at p<0.05.
      Data are reported as median and interquartile range (IR). RESULTS: Infants serum
      resistin concentration was 9.30 (5.02) ng/ml. Breast milk resistin concentration
      (n=23) was 0.18 (0.44) ng/ml. Leptin concentration was 3.04 (3.68) ng/ml in
      infants serum and in BM was 2.34 (5.73) ng/ml. Serum resistin concentrations in
      BF infants correlated positively with BM resistin (r=0.636, p=0.035). We have
      shown a positive correlation between resistin and leptin in total group of
      infants (r=0.44, p=0.05), confirmed in breastfed subjects (r=0.65, p=0.02). No
      correlations were found between serum hormones and anthropometric parameters of
      infants. CONCLUSION: Our findings show interestingly a positive correlation
      between resistin concentrations in BF infants serum and in BM and between
      resistin and leptin in infants.

PMID- 22641278
TI  - On ROC analysis with nonbinary reference standard.
AB  - Statistical methods for the evaluation of the accuracy of diagnostic tests
      usually assume a binary true disease status. However, this assumption may not be
      realistic in practical settings in which "disease" is defined by dichotomizing
      continuous or ordinal categorical measures using a pre-specified threshold value.
      In this paper, we focus on the analysis of studies in which both the diagnostic
      test and the reference standard are reported as continuous measures. We propose a
      semiparametric model for estimating the sensitivity, specificity, and the ROC
      curve as functions of reference standard thresholds. Under suitable order
      restrictions on the mean of the test result variable, fitting is done via two
      alternative approaches: isotonic regression and monotone smoothing splines. The
      model provides the basis to assess the effect of varying reference standard
      threshold on the performance of a diagnostic test. An example to evaluate the
      ability of the maximal SUV-lean (standardized uptake value normalized to lean
      body mass) in predicting axillary node involvement in women diagnosed with breast
      cancer is presented.

PMID- 22641279
TI  - Furan in heat-treated foods: formation, exposure, toxicity, and aspects of risk
      assessment.
AB  - Furan is formed in a variety of heat-treated foods through thermal degradation of
      natural food constituents. Relatively high levels of furan contamination are
      found in ground roasted coffee, instant coffee, and processed baby foods.
      European exposure estimates suggest that mean dietary exposure to furan may be as
      high as 1.23 and 1.01 MUg/kg bw/day for adults and 3- to 12-month-old infants,
      respectively. Furan is a potent hepatotoxin and hepatocarcinogen in rodents,
      causing hepatocellular adenomas and carcinomas in rats and mice, and high
      incidences of cholangiocarcinomas in rats at doses >= 2 mg/kg bw. There is
      therefore a relatively low margin of exposure between estimated human exposure
      and doses that cause a high tumor incidence in rodents. Since a genotoxic mode of
      action cannot be excluded for furan-induced tumor formation, the present
      exposures may indicate a risk to human health and need for mitigation. This
      review summarizes the current knowledge on mechanisms of furan formation in food,
      human dietary exposure to furan, and furan toxicity, and highlights the need to
      establish the risk resulting from the genotoxic and carcinogenic properties of
      furan at doses lower than 2 mg/kg bw.

PMID- 22641280
TI  - Myelodysplastic syndromes: the challenge of developing clinical guidelines and
      supportive care strategies for a rare disease.
AB  - Myelodysplastic syndromes (MDS) represent a group of clonal myeloid malignancies
      with variability in clinical presentation and disease trajectory, as well as
      prognosis and treatment recommendations (Kurtin & Demakos, 2010). MDS is
      considered to be a rare disease that is most common in adults older than age 70.
      The disease is characterized by ineffective hematopoiesis, progressive bone
      marrow failure, and a variable risk of leukemic transformation thought to result
      from complex interactions between the malignant clone and the bone marrow
      microenvironment (Kurtin, 2011). This supplement is intended to provide the
      oncology clinician with an overview of MDS and provide tools for the clinical
      management and support of patients with MDS.

PMID- 22641281
TI  - Update on the science of myelodysplastic syndromes.
AB  - Scientific research is only just beginning to shed light on the pathobiology
      underlying the various subtypes of myelodysplastic syndromes (MDS), a
      heterogeneous group of clonal stem cell disorders characterized by cytopenias
      that can progress to acute myeloid leukemia. Increased understanding of the
      disease and prognostic implications of specific clinical features has aided in
      the development of prescribing guidelines and new treatments for MDS. Because
      oncology nurses have frequent interactions with patients during diagnostic and
      therapeutic evaluations, an understanding of the science behind disease
      classification, prognostic scoring, and the goals of treatment for low- and high
      risk disease is important to answer questions regarding diagnostic results,
      treatment outcomes, and adverse event monitoring.

PMID- 22641282
TI  - Treatment of myelodysplastic syndromes: practical tools for effective management.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid malignancies
      with variability in clinical presentation, disease trajectory, treatment goals,
      and expected outcomes. The treatment of patients with MDS, therefore, often
      differs from patient to patient. Tools are needed to aid effective communication
      with patients, their caregivers, and their dedicated team of healthcare
      professionals. The use of methods often employed in clinical trials can help
      healthcare providers diagnose and classify risk status, track trends within
      patient responses, manage adverse events, set treatment expectations, and provide
      ongoing supportive care. This article discusses several tools and strategies
      available for the management of patients with MDS throughout the continuum of
      their disease.

PMID- 22641283
TI  - Management of transfusion-related iron overload in patients with myelodysplastic
      syndromes.
AB  - Anemia is a common symptom for patients with myelodysplastic syndromes (MDS), a
      spectrum of hematopoietic malignancies characterized by ineffective
      hematopoiesis; 90% of these patients will become transfusion dependent (TD).
      Because of the closed nature of iron metabolism, the repeated input of packed red
      blood cells during transfusions inevitably leads to iron overload. Iron overload
      can cause iron-related toxicity as well as end-organ damage from iron deposition
      in tissues. Studies have shown that patients with MDS who are TD have shorter
      overall survival, shorter leukemia-free survival, and higher healthcare costs
      compared with patients who are not TD, suggesting that iron overload has a
      significant clinical and economic impact. Iron chelation therapy can bind and
      eliminate free iron from the body. Although studies in genetic anemias have shown
      improved clinical outcomes, clinical trials with patients with MDS are ongoing.
      Because iron chelation therapy can be toxic, the risks, benefits, and therapy
      related costs must be weighed for each patient.

PMID- 22641284
TI  - The importance of quality of life for patients living with myelodysplastic
      syndromes.
AB  - Myelodysplastic syndromes (MDS) are a group of myeloid stem cell clonal disorders
      characterized by a wide variation in illness trajectory and potential treatment.
      The physical, functional, emotional, social, and spiritual well-being of
      individuals with MDS can be affected by both disease and treatment-related
      factors. As a result, the quality of life (QOL) in patients with MDS may vary
      throughout the course of the illness. To date, most research exploring QOL in
      patients with MDS has been conducted as part of clinical trials evaluating the
      effectiveness of a therapeutic intervention. Although data from those studies are
      useful, they do not fully address the issues critical to maintaining or
      maximizing QOL. Oncology nurses are in a key position to assist patients with MDS
      to maintain their QOL. Findings from comprehensive QOL assessments will guide
      nurses in providing relevant interventions and evaluating their outcomes. In this
      manner, oncology nurses can assist their patients to maximize QOL while living
      with this challenging illness.

PMID- 22641285
TI  - Patient and family resources for living with myelodysplastic syndromes.
AB  - Primarily a disease affecting older adults, myelodysplastic syndromes (MDS) are a
      class of incurable myeloid malignancies with variable clinical presentation,
      treatment recommendations, and prognoses. Although effective communication
      between healthcare professionals and patients and their caregivers is a
      significant part of optimizing clinical outcomes, studies have shown that all
      three frequently have an incomplete understanding of MDS, its therapeutic
      options, and the fact that MDS is a malignancy. In addition, the advanced age of
      the patient population, high frequency of comorbidities, and variability of
      disease outcomes based on risk status require consistent communication across a
      wide number and type of healthcare providers as well as an individualized
      approach to patient and caregiver education. This article discusses these
      challenges and provides a number of resources designed to help educate healthcare
      professionals, patients, and caregivers.

PMID- 22641286
TI  - Targeted molecular therapies for ovarian cancer: an update and future
      perspectives (Review).
AB  - Identification of the potential gene expression profiles of epithelial ovarian
      cancer and the arrival of newly targeted therapies have advanced the strategies
      used for treatment of this disease. This review focuses on the design of ongoing
      and planned clinical trials and offers a synopsis of the English-language
      literature for preclinical and clinical targeted therapies for epithelial ovarian
      cancer. Among many targeted agents, a promising, novel class of targeted drugs
      for special patient populations expected to improve the effectiveness of current
      therapy include inhibitors of angiogenesis, poly (ADP ribose) polymerase (PARP)
      and DNA repair mechanisms. Inhibition of PARP or homologous recombination (HR)
      repair mediated by Chk1 (checkpoint kinase 1) would selectively sensitize p53
      mutation, BRCAness phenotype (serous type ovarian cancer) or HNF (hepatocyte
      nuclear factor)-1beta-overexpressing tumor cells (clear cell type ovarian cancer)
      to chemotherapeutic agents. The therapeutic response is likely to be limited to a
      targeted patient, but not to the broad population. This review discusses some of
      the key current developments and existing challenges.

PMID- 22641287
TI  - uPAR and cathepsin B knockdown inhibits radiation-induced PKC integrated integrin
      signaling to the cytoskeleton of glioma-initiating cells.
AB  - Despite advances in radiotherapeutic and chemotherapeutic techniques and
      aggressive surgical resection, the prognosis of glioblastoma patients is dismal.
      Accumulation of evidence indicates that some cancer cells survive even the most
      aggressive treatments, and these surviving cells, which are resistant to therapy
      and are perhaps essential for the malignancy, may be cancer stem cells. The CD133
      surface marker is commonly used to isolate these extremely resistant glioma
      initiating cells (GICs). In the present study, GICs which tested positive for the
      CD133 marker (CD133+) were isolated from both the established U251 cell line and
      the 5310 xenograft glioma cell line to study the events related to the molecular
      pathogenesis of these cells. Simultaneous down-regulation of uPAR and cathepsin B
      by shRNA (pUC) treatment caused the disruption of radiation-induced complex
      formation of pPKC theta/delta, integrin beta1 and PKC zeta, integrin beta1 in
      glioma cells. Further, pUC treatment inhibited PKC/integrin signaling via FAK by
      causing disassociation of FAK and the cytoskeletal molecules vinculin and alpha
      actinin. Also, we observed the inhibition of ERK phosphorylation. This inhibition
      was mediated by pUC and directed a negative feedback mechanism over the FAK
      signaling molecules, which led to an extensive reduction in the signal for
      cytoskeletal organization generating migratory arrest. Altogether, it can be
      hypothesized that knockdown of uPAR and cathepsin B using shRNA is an effective
      strategy for controlling highly invasive glioma cells and extremely resistant
      glioma-initiating cells.

PMID- 22641288
TI  - [Dendritic cell-based therapeutic vaccination for acute myeloid leukemia].
AB  - The long-term outlook for adult patients with acute myeloid leukemia (AML)
      remains dismal. The main reason for this state of affairs lies in the fact that
      the majority of AML patients will eventually relapse, even after obtaining
      complete remission following front-line chemotherapy. Relapses are generally
      attributed to the persistence of a small number of chemotherapy-resistant
      leukemic (stem) cells, a condition known as minimal residual disease (MRD). The
      eradication of MRD, with the eventual aim of reducing the risk of relapse,
      therefore represents a high-priority goal of modern AML therapy. It is now well
      established that the immune system plays a crucial role in the defense against
      AML. This knowledge has fuelled the development of immune-based approaches to
      control MRD and, ultimately, to prevent relapse. One of the promising strategies
      that have emerged in this regard involves the use of dendritic cells for
      therapeutic vaccination. This review article aims to introduce the reader into
      the conceptual and practical aspects of DC-based vaccination for AML. Next, we
      will review the first clinical results obtained with this immunotherapeutic
      approach in AML patients. Finally, we will briefly reflect on the potential place
      of DC vaccination in the future therapy of AML.

PMID- 22641289
TI  - Synthesis and evaluation of new polyenic compounds as potential PPARs modulators.
AB  - In order to identify new leads for the treatment of type 2 diabetes, polyenic
      molecules A and B derived from nipecotic acid and dienol derivatives C have been
      prepared and their effect on PPARs transcriptional activity evaluated and
      compared to that of rosiglitazone, WY14,643 and GW501516. Among the synthesized
      compounds, dienol 39 is the most active, increasing WY14,643 PPARalpha response
      and demonstrating partial agonist properties on rosiglitazone PPARgamma.

PMID- 22641290
TI  - Metals on graphene: correlation between adatom adsorption behavior and growth
      morphology.
AB  - We present a systematic study of metal adatom adsorption on graphene by ab initio
      calculations. The calculations cover alkali metals, sp-simple metals, 3d and
      group 10 transition metals, noble metals, as well as rare earth metals. The
      correlation between the adatom adsorption properties and the growth morphology of
      the metals on graphene is also investigated. We show that the growth morphology
      is related to the ratio of the metal adsorption energy to its bulk cohesive
      energy (E(a)/E(c)) and the diffusion barrier (DeltaE) of the metal adatom on
      graphene. Charge transfer, electric dipole and magnetic moments, and graphene
      lattice distortion induced by metal adsorption would also affect the growth
      morphologies of the metal islands. We also show that most of the metal
      nanostructures on graphene would be thermally stable against coarsening.

PMID- 22641291
TI  - Fludarabine nucleoside induces accumulations of p53, p63 and p73 in the nuclei of
      human B-lymphoid cell lines, with cytosolic and mitochondrial increases in p53.
AB  - PURPOSE: Human Raji cells treated with fludarabine nucleoside (2-FaraA, 3 MUM)
      undergo apoptosis with accumulation of p53 in the nuclei as multiple
      phosphorylated isoforms and C-terminal truncated derivatives. Changes induced by
      2-FaraA in the levels of p53, p63 and p73 in the nuclear, cytosolic and
      mitochondrial fractions have been determined in four human B-lymphoid cell lines
      that are TP53-functional (Raji and IM9) and TP53-mutated (MEC1 and U266).
      EXPERIMENTAL DESIGN: The B-lymphoid cell lines were treated with 2-FaraA (3 MUM,
      24 h, 48 h) and viability determined. Protein extracts of subcellular fractions
      from 2-FaraA-treated cells were analysed by 1D and 2D electrophoresis; multiple
      phosphorylated isoforms and truncated derivatives were identified by Western
      blots for p53, p63 and p73. RESULTS: p53 and p63 were present in all three
      fractions, while p73 was only detected in nuclei. After treatment with 2-FaraA,
      nuclear p53, p63 and p73 accumulated as multiple phosphorylated isoforms and
      truncated derivatives. The association of p63 with mitochondria in human cells is
      novel. CONCLUSIONS AND CLINICAL RELEVANCE: Comprehensive information on the
      subcellular distributions and responses of p53, p63 and p73 to 2-FaraA provides
      additional insight into mechanisms for induction of apoptosis in the treatment of
      B-lymphoproliferative disorders with fludarabine.

PMID- 22641293
TI  - In situ investigation of dye adsorption on TiO2 films using a quartz crystal
      microbalance with a dissipation technique.
AB  - Dye adsorption plays a crucial role in dye-sensitized solar cells. Herein, we
      demonstrate an in situ liquid-phase analytical technique to quantify in real time
      adsorption of dye and coadsorbates on flat and mesoporous TiO(2) films. For the
      first time, a molar ratio of co-adsorbed Y123 and chenodeoxycholic acid has been
      measured.

PMID- 22641292
TI  - Comparison of outcomes after allogeneic hematopoietic stem cell transplantation
      in patients with follicular lymphoma, diffuse large B-cell lymphoma associated
      with follicular lymphoma, or de novo diffuse large B-cell lymphoma.
AB  - The outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT)
      for diffuse large B-cell lymphoma (DLBCL) associated with follicular lymphoma
      (FL), which includes DLBCL with pre- or co-existing FL, remains controversial,
      and few previous reports have compared the outcomes after allo-HCT for FL, DLBCL
      associated with FL, and de novo DLBCL. We retrospectively analyzed 97 consecutive
      patients with FL (n = 46), DLBCL associated with FL (n = 22), or de novo DLBCL (n
      = 29) who received allo-HCT at our institute between 2000 and 2010. With a median
      follow-up of 53 months, the 5-year overall survival (OS) and progression-free
      survival (PFS) were, respectively, 77% and 70% for FL, 62% and 57% for DLBCL
      associated with FL, and 26% and 23% for de novo DLBCL. The 5-year cumulative
      incidences of non-relapse mortality and disease progression/relapse were,
      respectively, 16% and 15% for FL, 19% and 24% for DLBCL associated with FL, and
      36% and 41% for de novo DLBCL. By a multivariate analysis, the OS and PFS for
      DLBCL associated with FL were significantly better than those for de novo DLBCL,
      whereas they were not significantly different from those for FL. These results
      suggest that allo-HCT may be a promising option for patients with not only
      advanced FL but also DLBCL associated with FL.

PMID- 22641294
TI  - Investigation of the different stable states of the cantilever oscillation in an
      atomic force microscope.
AB  - We present an algorithm which allows us to identify all possible stable states of
      the cantilever oscillation of an AFM operated in the intermittent contact mode
      within the harmonic approximation. The oscillatory states are qualified as quasi
      free, net-attractive and net-repulsive solutions. Using a generic model for the
      tip-sample interaction the influence of a number of important experimental
      parameters on the state of oscillation is systematically studied. The analysis
      gives conditions under which an AFM can be operated in a chosen state. As an
      exemplary experimental application we compare selected measurements on a
      semicrystalline polymer acquired in the net-repulsive and the net-attractive mode
      with simulations based on the approach introduced here. The experiments indicate
      that a small indentation below one nanometer in the net-attractive mode is enough
      to produce phase contrast.

PMID- 22641295
TI  - A novel photoanode with three-dimensionally, hierarchically ordered nanobushes
      for highly efficient photoelectrochemical cells.

PMID- 22641299
TI  - Non-lesional white matter changes in pediatric multiple sclerosis and monophasic
      demyelinating disorders.
AB  - OBJECTIVE: To analyze diffusion tensor imaging (DTI) derived metrics between
      patients with childhood onset multiple sclerosis (MS), monophasic demyelinating
      illnesses, and healthy controls. BACKGROUND: Monophasic demyelinating illnesses
      can be indistinguishable clinically and radiologically, utilizing standard MRI
      studies. DTI studies in adults implicate the involvement of normal-appearing
      white matter (NAWM) in MS. METHODS: Subjects with DTI studies (15 directions, 1.5
      Tesla (GE), 3x3x3 mm, interpolated to 1.5x1.5x3 mm) were retrospectively
      identified. We studied three groups: childhood onset MS (n=18), monophasic
      illness (eight with acute disseminated encephalomyelitis (ADEM), seven with
      clinically isolated syndrome (CIS)) and age-matched controls. DTI had been
      obtained within one month of symptom onset for patients with ADEM and within a
      median of 20 months for the MS group. DTI measures were determined using a semi
      automated method from standardized regions of interest (ROI) containing central
      fibers of the corpus callosum genu and internal capsule. RESULTS: The MS group
      had significantly lower fractional anisotropy (FA) values compared to controls
      (p<0.001), with increased radial diffusivity (RD) and decreased axial diffusivity
      (AD). In the monophasic group FA was smaller than the controls (p=0.01) with
      increased RD and no difference in AD. CONCLUSIONS: This retrospective analysis
      provides evidence that NAWM is affected in pediatric MS and monophasic
      demyelinating disease, with a potentially novel pattern demonstrating reduced AD
      in pediatric MS. Further larger scale confirmatory studies are needed to address
      whether the demonstrated DTI changes could be used as a biomarker in pediatric
      patients presenting with an initial demyelinating event.

PMID- 22641300
TI  - Evaluation of pattern-reversal visual evoked potential in patients with
      neuromyelitis optica.
AB  - BACKGROUND: The visual evoked potential (VEP) is used in the evaluation of
      multiple sclerosis (MS) patients, showing a delay in P100 wave latency with no
      changes in amplitude in 60-100% of cases. In the last decade, the recurrent form
      of neuromyelitis optica (NMO) has been recognized, and clinically characterized
      by acute events of transverse myelitis (TM) and optic neuritis (ON), differing
      from MS in clinical and laboratory criteria. Despite these differences, so far,
      the VEP parameters described in MS have been used in the evaluation of patients
      with NMO. The objective of this study was to investigate VEP responses in NMO.
      METHODS: Patients with NMO underwent pattern-reversal visual stimulation.
      Nineteen patients were selected for the study. RESULTS: Among the 38 eyes
      examined, 18 (47.4%) had no visual evoked responses and 13 (34.2%) had a
      reduction of P100 wave amplitude with normal latency. Only two (5.3%) had the
      pattern described in MS and five (13.2%) were normal. CONCLUSION: Evaluation of
      VEP in patients with definite NMO revealed a pattern that is different from that
      of MS in 81.6% of eyes examined, characterized by the absence of responses, or
      decreased amplitude with normal latency.

PMID- 22641301
TI  - A serial in vivo 7T magnetic resonance phase imaging study of white matter
      lesions in multiple sclerosis.
AB  - BACKGROUND: Magnetic resonance (MR) phase imaging using high field MR scanners
      has demonstrated excellent contrast in multiple sclerosis (MS) lesions that is
      thought to be closely correlated to the local iron content. This pilot study
      acquired serial in vivo MR scans at 7T to track the evolution of phase contrast
      as MS lesions progress. METHODS: Five MS patients with relapsing-remitting MS
      were serially scanned for about 2.5 years at 7T using a high resolution T2*
      weighted gradient-echo sequence. Magnitude and phase images were reconstructed
      for each scan and co-registered to their baseline study. RESULTS: Five non
      enhancing ring and 70 nodular phase lesions were found in the five patients at
      baseline. None of the baseline phase lesions (including all five ring phase
      lesions) showed obvious qualitative variation on phase images during the study.
      Of note, we observed that three magnitude lesions, not initially read as abnormal
      signal, were either better appreciated using phase contrast imaging (two lesions)
      or preceded (one lesion) by phase changes. CONCLUSION: The observation that ring
      phase lesions remained unchanged over 2.5 years of follow-up challenges the
      notion that such lesions reveal the presence of acute activated iron-rich
      macrophages. It suggests that either different phenotypes of macrophages persist
      longer than previously expected or other mechanisms related to tissue injury
      contribute to the phase contrast.

PMID- 22641302
TI  - 7 Tesla MRI demonstrates vascular pathology in Balo's concentric sclerosis.
AB  - Balo's concentric sclerosis (BCS) is an inflammatory demyelinating disease
      related to multiple sclerosis; its underlying pathology remains unclear. At 7 T
      MRI in a 19-year-old female BCS patient, microhaemorrhages and ectatic veins were
      found in T2 hyperintense regions, features which have not been previously
      reported in conjunction with BCS, and these findings may support the view that
      vascular pathology plays a role in BCS. MRS data suggest that neuron loss and
      lipid turnover still took place months after a remission. Plasma exchange was
      effective in treating a relapse with severe motor deficits, and the off-label use
      of natalizumab was successful in maintaining remission in this patient.

PMID- 22641304
TI  - Desensitization to natalizumab: clinical and immunological observations.

PMID- 22641303
TI  - Caffeine and alcohol intakes have no association with risk of multiple sclerosis.
AB  - BACKGROUND: The association between alcohol and caffeine intakes and risk of
      multiple sclerosis (MS) is unclear; no prospective studies have examined this
      relationship. OBJECTIVE: We examined intakes of alcohol and caffeine in relation
      to risk of multiple sclerosis. METHODS: Intakes of alcohol and caffeine were
      examined in relation to the risk of MS in two large cohorts of women, the Nurses'
      Health Study (NHS; 92,275 women followed from 1980 to 2004) and Nurses' Health
      Study II (NHS II; 95,051 women followed from 1991 to 2005). Their diet was
      assessed at baseline and every four years thereafter. During the follow-up, 282
      cases of MS were confirmed with onset of symptoms after baseline. Twenty-four
      cases were missing information on alcohol intake, leaving a total of 258 cases
      for the alcohol analyses. RESULTS: Neither total alcohol consumption, nor
      consumption of beer, wine, or liquor was related to MS risk. The multivariable
      adjusted pooled relative risk (RR) found by comparing categories of alcohol
      intake to 0 gm/day was 1.07 (95% CI: 0.32-1.99) for 0.1-4.9 gm/day, 1.01 (0.32
      1.99) for 5.0-14.9 gm/day, 1.21 (0.69-2.15) for 15.0-29.9 gm/day, and 0.80 (0.32
      1.99) for 30+ gm/day; (p for trend=0.89). Caffeine intake was also not
      significantly associated with MS risk. The multivariable adjusted pooled RR
      comparing highest to lowest quintile of caffeine intake was 1.14; 95% CI: 0.79
      1.66; p for trend=0.71. Consideration of caffeinated and decaffeinated coffee
      separately also yielded null results. CONCLUSION: These results do not support an
      association between alcohol and caffeine intakes and MS risk.

PMID- 22641305
TI  - Zero-inflated endogenous count in censored model: effects of informal family care
      on formal health care.
AB  - If informal family health care is a substitute for formal health care, then there
      is a scope to reduce formal health care cost by promoting informal family health
      care. With the use of Korean data for the elderly, this paper estimates the
      effects of informal family health care on formal health care, where the former is
      measured by the number of caregivers and the latter is measured by the formal
      health care expenditure. This task, however, poses a number of difficulties. The
      first is that the number of the family caregivers is an endogenous count
      regressor. The second is that there are too many zeros in the count (85%). The
      third is that the response variable also has a nontrivial proportion of zeros
      (14%). This paper overcomes these problems by combining 'control function
      approach', 'zero-inflated' counts, and a semiparametric estimator for censored
      models. The resulting procedure avoids strong parametric assumptions and behaves
      well computationally. Our main empirical finding is that informal family health
      care has a large substitute effect for diabetics and that there are also weak
      evidences that informal family health care has substitute effects for high blood
      pressure and mental diseases.

PMID- 22641306
TI  - Capnographic monitoring reduces the incidence of arterial oxygen desaturation and
      hypoxemia during propofol sedation for colonoscopy: a randomized, controlled
      study (ColoCap Study).
AB  - OBJECTIVES: The aim of this randomized study was to determine whether
      intervention based on additional capnographic monitoring reduces the incidence of
      arterial oxygen desaturation during propofol sedation for colonoscopy. METHODS:
      Patients (American Society of Anesthesiologists classification (ASA) 1-3)
      scheduled for colonoscopy under propofol sedation were randomly assigned to
      either a control arm with standard monitoring (standard arm) or an interventional
      arm in which additional capnographic monitoring (capnography arm) was available.
      In both study arms, detection of apnea or altered respiration induced withholding
      propofol administration, stimulation of the patient, chin lift maneuver, or
      further measures. The primary study end point was the incidence of arterial
      oxygen desaturation (defined as a fall in oxygen saturation (SaO(2)) of >=5% or
      <90%); secondary end points included the occurrences of hypoxemia (SaO(2) <90%),
      severe hypoxemia (SaO(2) <=85%), bradycardia, hypotension, and the quality of
      sedation (patient cooperation and patient satisfaction). RESULTS: A total of 760
      patients were enrolled at three German endoscopy centers. The intention-to-treat
      analysis revealed a significant reduction of the incidence of oxygen desaturation
      in the capnography arm in comparison with the standard arm (38.9% vs. 53.2%;
      P<0.001). The numbers of patients with a fall in SaO(2) <90% and <=85% were also
      significantly different (12.5% vs. 19.8%; P=0.008 and 3.7 vs. 7.8%; P=0.018).
      There were no differences regarding the rates of bradycardia and hypotension.
      Quality of sedation was similar in both groups. Results of statistical analyses
      were maintained for the per-protocol population. CONCLUSIONS: Additional
      capnographic monitoring of ventilatory activity reduces the incidence of oxygen
      desaturation and hypoxemia during propofol sedation for colonoscopy.

PMID- 22641307
TI  - Influence of acupuncture treatment on cerebral activity in functional dyspepsia
      patients and its relationship with efficacy.
AB  - OBJECTIVES: Acupuncture is a commonly used therapy for treating functional
      dyspepsia (FD), although the mechanism remains unclear. The objectives of this
      study were to investigate the differences in cerebral glycometabolism changes
      evoked by acupuncture and sham acupuncture and to explore the possible
      correlations between brain responses and clinical efficacy. METHODS: In all, 72
      FD patients were randomly assigned to receive either acupuncture or sham
      acupuncture treatment for 4 weeks. Ten patients in each group were randomly
      selected for fluorine-18 fluorodeoxyglucose positron emission tomography computed
      tomography scans to detect cerebral glycometabolism changes. The Nepean Dyspepsia
      Index (NDI) and Symptom Index of Dyspepsia (SID) were used to evaluate the
      therapeutic effect. RESULTS: (i) The clinical data showed that after treatment
      the decrease in SID score in the acupuncture group was significantly greater than
      that in the sham acupuncture group (P<0.05). The increase in NDI score between
      the two groups did not differ (P>0.05), and only the improvement in NDI score in
      the acupuncture group was clinically significant. (ii) The neuroimaging data
      indicated that after treatment the acupuncture group showed extensive
      deactivation in cerebral activities compared with the sham acupuncture group. In
      the acupuncture group, the deactivations of the brainstem, anterior cingulate
      cortex (ACC), insula, thalamus, and hypothalamus were nearly all related to the
      decrease in SID score and the increase in NDI score (P<0.05, corrected). In the
      sham acupuncture group, the deactivations of the brainstem and thalamus tended to
      be associated with the increase in NDI score (P<0.1, corrected). CONCLUSIONS:
      Acupuncture and sham acupuncture have relatively different clinical efficacy and
      brain responses. Acupuncture treatment more significantly improves the symptoms
      and quality of life of FD patients. The more remarkable modulation on the
      homeostatic afferent network, including the insula, ACC, and hypothalamus, might
      be the specific mechanism of acupuncture.

PMID- 22641308
TI  - Rapid point-of-care first-line screening tests for hepatitis B infection: a meta
      analysis of diagnostic accuracy (1980-2010).
AB  - OBJECTIVES: Three-hundred fifty million people worldwide are chronically infected
      with Hepatitis B, with four million acute infections annually. With infection
      concentrated in hard-to-reach populations and low resource settings, rapid point
      of-care (POC) tests offer an efficient screening alternative to laboratory tests.
      We conducted a meta-analysis to evaluate accuracy of rapid POC tests screening
      for Hepatitis B. METHODS: Two reviewers searched four databases, critiqued
      quality. A hierarchical Bayesian meta-analysis correcting for imperfect reference
      standards was used. Based on components of the antigen-antibody response, 17
      studies were stratified into three subgroups: (i) Hepatitis B surface antigen
      (HBsAg) tests; (ii) anti-HBsAg tests, and (iii) HBs+eAg tests. Further, we pooled
      estimates on individual tests with sufficient data. RESULTS: In subgroup 1, the
      pooled sensitivity (Sn) was 94.76% (95% credible interval (CrI): 90.08-98.23%)
      and specificity (Sp) was 99.54% (95% CrI: 99.03-99.95%). The Determine test
      reported a pooled Sn 98.2% (95% CrI: 94.7, 99.9) and Sp 99.9% (95% CrI: 99.3,
      100); in subgroup 2, Sn 93.2% (95% CrI: 85.1, 98.5), Sp 93.1% (95% CrI: 81.9,
      99.9); and in subgroup 3, the Binax test showed Sn 95.5% (95% CrI: 88.9, 99.4),
      Sp 99.8% (95% CrI: 99.3, 100). CONCLUSIONS: HBsAg tests, including Determine, and
      the HBs+eAg test, Binax showed high accuracy. Improvements in sensitivity of
      antibody-based tests will enhance their potential for global first-line
      screening.

PMID- 22641309
TI  - The diagnosis and management of non-alcoholic fatty liver disease: Practice
      guideline by the American Association for the Study of Liver Diseases, American
      College of Gastroenterology, and the American Gastroenterological Association.

PMID- 22641310
TI  - Dose-response relationship from longitudinal data with response-dependent dose
      modification using likelihood methods.
AB  - In some clinical trials or clinical practice, the therapeutic agent is
      administered repeatedly, and doses are adjusted in each patient based on
      repeatedly measured continuous responses, to maintain the response levels in a
      target range. Because a lower dose tends to be selected for patients with a
      better outcome, simple summarizations may wrongly show a better outcome for the
      lower dose, producing an incorrect dose-response relationship. In this study, we
      consider the dose-response relationship under these situations. We show that
      maximum-likelihood estimates are consistent without modeling the dose
      modification mechanisms when the selection of the dose as a time-dependent
      covariate is based only on observed, but not on unobserved, responses, and
      measurements are generated based on administered doses. We confirmed this
      property by performing simulation studies under several dose-modification
      mechanisms. We examined an autoregressive linear mixed effects model. The model
      represents profiles approaching each patient's asymptote when identical doses are
      repeatedly administered. The model takes into account the previous dose history
      and provides a dose-response relationship of the asymptote as a summary measure.
      We also examined a linear mixed effects model assuming all responses are measured
      at steady state. In the simulation studies, the estimates of both the models were
      unbiased under the dose modification based on observed responses, but biased
      under the dose modification based on unobserved responses. In conclusion, the
      maximum-likelihood estimates of the dose-response relationship are consistent
      under the dose modification based only on observed responses.

PMID- 22641311
TI  - Inotilone suppresses phorbol ester-induced inflammation and tumor promotion in
      mouse skin.
AB  - SCOPE: Chemoprevention is one of the most feasible approaches to reduce the risk
      of cancer. Over the past decades, scientists have realized that chronic
      inflammation is a critical component of cancer development. Inotilone, existing
      in Inonotus mushroom has been reported to exhibit anti-inflammatory properties in
      vitro. Hence, we investigated the effects of inotilone on 12-O
      tetradecanoylphorbol-13-acetate (TPA)-mediated acute inflammation and tumor
      promotion in mouse skin and the underlying molecular mechanisms. METHODS AND
      RESULTS: Inotilone was topically applied to mouse skin 30 min prior to TPA
      treatment. The results have shown that inotilone inhibited the production of
      inflammatory mediators by attenuating the activation of nuclear factor-kappaB (NF
      kappaB) and the expression of CCAAT/enhancer binding protein beta (C/EBPbeta).
      Furthermore, the ability of inotilone to prevent tumorigenesis at promotion stage
      was evaluated using a classical two-stage mouse skin carcinogenesis model. After
      initiation of 7,12-dimethylbenz[a]anthracene (DMBA), applying inotilone topically
      before each TPA treatment was found to reduce the tumor incidence and tumor
      multiplicity of papillomas. CONCLUSION: Based on the results, we concluded that
      inotilone has potential to be developed into an effective chemopreventive agent
      for the treatment of a variety of inflammatory diseases, especially the
      prevention and treatment of epithelial skin cancer.

PMID- 22641312
TI  - Ask us: we know about psychosocial care.
AB  - Oncology nurses have always known that a diagnosis of cancer impacts the
      psychosocial well-being of a person. And, often, oncology nurses are the ones who
      detect psychosocial concerns in patients, as well as noticing changes-often
      subtle differences in a patient's usual manner-which require further assessment
      and possibly referral or treatment.

PMID- 22641313
TI  - Drug shortages add to the stress of treatment.

PMID- 22641314
TI  - The changing hope trajectory in patients with advanced-stage cancer: a nursing
      perspective.
AB  - As patients with advanced-stage cancer move from the initial diagnosis through
      treatment, remission, recurrence, and advanced-stage disease, the hope trajectory
      undergoes a dynamic transformation. By identifying the hope trajectory, nurses
      can help patients focus on obtainable hope objects while balancing the need to
      present a realistic prognosis. This, in turn, may help patients find meaning and
      purpose in advanced-stage cancer and facilitate realistic hope when faced with a
      life-threatening illness.

PMID- 22641315
TI  - Symptom management excellence initiative: promoting evidence-based oncology
      nursing practice.
AB  - Accessing and using the best evidence for cancer symptom interventions are
      prerequisites for nursing excellence. To incorporate evidence into direct care
      practice, staff at the Dana-Farber Cancer Institute implemented the Symptom
      Management Excellence initiative to compare patients' and nurses' reports of
      their most frequent and highest priority cancer symptoms. Interdisciplinary teams
      then convened to design and test the feasibility of bringing symptom management
      evidence into clinical practice. This article describes how the initiative has
      successfully used patient-reported data, direct-care nurse input, research
      evidence, and expert opinion to systematically improve cancer symptom management.

PMID- 22641316
TI  - Safe handling: implementing hazardous drug precautions.
AB  - Occupational exposure to chemotherapy is a significant and ubiquitous danger to
      oncology nurses. The Oncology Clinical Nurse III/IV leadership group at the
      University of North Carolina Hospitals embarked on the challenge of a
      comprehensive standards review regarding personal protective equipment necessary
      when handling waste after hazardous drug administration. This review led to
      practice improvements in education, the use of chemotherapy-rated gloves when
      handling hazardous waste, and changes in the disposal options available to staff.
      A discharge teaching pamphlet on safe handling for the caregivers of patients
      receiving hazardous drugs was created and piloted.

PMID- 22641317
TI  - Etiology, assessment, and management of aromatase inhibitor-related
      musculoskeletal symptoms.
AB  - Aromatase inhibitors (AIs) are recommended as adjuvant endocrine therapy for
      postmenopausal women with hormone-responsive breast cancer. With the widespread
      use of AI adjuvant endocrine therapy, a significant profile of musculoskeletal
      symptoms has emerged. Moderate to severe musculoskeletal symptoms have led some
      women to discontinue therapy, compromising the survival benefit. The etiology of
      AI-related musculoskeletal symptoms is poorly understood, which challenges
      development of effective management strategies. The purpose of this article is to
      describe AI-related musculoskeletal symptoms, review possible causes, provide
      assessment guidelines, and recommend management strategies based on the best
      available evidence. Little evidence exists for effective management strategies of
      AI-related musculoskeletal symptoms, and randomized clinical trials are needed to
      establish effective interventions. A thorough musculoskeletal assessment can help
      guide clinical decision making for the best individual management approach.
      Providers need to manage symptoms with the best available evidence to minimize
      symptom distress and maximize adherence to AI therapy.

PMID- 22641318
TI  - Uterine leiomyosarcoma: diagnosis, treatment, and nursing management.
AB  - Uterine leiomyosarcoma is a rare form of sarcoma with limited treatment options
      and a high potential for distant recurrence. At the time of diagnosis, swift
      action should be taken to initiate treatment. Options for treatment include
      surgical debulking and disease staging, radiation therapy, and/or chemotherapy.
      The purpose of this article is to review the disease epidemiology, presentation
      at diagnosis, surgical staging, and prognosis. Treatment options and the role of
      targeted therapies are discussed in addition to the various nursing implications
      associated with management of the disease.

PMID- 22641319
TI  - Women's poorer satisfaction with their sex lives following gynecologic cancer
      treatment.
AB  - Gynecologic cancer treatment can lead to anatomical changes in the genitalia that
      may impair sexual response. As a result, the authors aimed to assess women's self
      perceptions of their sex lives following gynecologic cancer treatment and the
      impact of such treatment on sexual function. Thirty sexually active women were
      examined. At the first meeting with a physician sex therapist, women were asked
      about their satisfaction with their sexual activities prior to and after
      gynecologic cancer treatment, either with a partner or alone, and how many times
      per month they had sexual intercourse prior to the cancer diagnosis and after
      treatment. Women reported significantly worse sex lives and a significantly lower
      frequency of sexual relations following cancer treatment. All participants
      reported pain on vaginal penetration and feeling uncomfortable in discussing
      their sexual difficulties with the oncologist. The findings show that women
      experienced impaired sexual function, as well as poorer quality of sexual
      function, following gynecologic cancer treatment. Nurses should provide basic
      guidelines about sexual function to all patients who undergo treatment for
      gynecologic cancer.

PMID- 22641320
TI  - A feasibility study of low-cost, self-administered skin care interventions in
      patients with head and neck cancer receiving chemoradiation.
AB  - Current evidence for the management of radiation skin toxicities demonstrates
      equivocal outcomes using a variety of interventions, leaving substantial gaps in
      knowledge. Skin toxicities can lead to treatment delays, infection, pain, and
      increased costs for the patient. Patients with head and neck cancers receiving
      chemoradiation (N = 100), a population particularly vulnerable to disruptions in
      skin integrity, were enrolled into a prospective, descriptive study. Data
      collection was conducted and photographs were taken at baseline and weekly
      throughout treatment. Patients received skin care kits, instructions, and a diary
      to record adherence. Skin toxicity was measured and validated by at least three
      observers using serial photographs with 100% interrater agreement. Data were
      analyzed using descriptive statistics, graphs, and bivariate analysis. Adherence
      to both washing and moisturizing was consistently high. Although a correlation
      existed between the radiation dose and skin toxicity at week 6, no correlation
      existed between skin toxicity and adherence. Given the rate of grade 3 toxicities
      at week 6 and product costs, this proved to be an affordable regimen to which
      patients could easily adhere. Positive patient outcomes can be promoted through
      teaching and reinforcement of self-care measures to reduce skin toxicity.

PMID- 22641321
TI  - Managing side effects of the novel taxane cabazitaxel in castrate-resistant
      prostate cancer.
AB  - Cabazitaxel, a novel taxane, was approved in June 2010 by the U.S. Food and Drug
      Administration for treatment of metastatic castrate-resistant prostate cancer
      (mCRPC) in men previously treated with docetaxel. In TROPIC (N = 755), an open
      label, randomized, phase III trial, cabazitaxel (plus prednisone) was associated
      with improvement in median overall survival compared with mitoxantrone plus
      prednisone (15.1 versus 12.7 months, p < 0.0001) in patients with mCRPC who had
      progressed following docetaxel-based regimens. That corresponds to a 30% relative
      reduction in risk of death compared with the mitoxantrone regimen. In addition,
      significant benefit existed in median progression-free survival with cabazitaxel
      versus the mitoxantrone regimen (2.8 versus 1.4 months, p < 0.0001). Most common
      adverse events (AEs) associated with cabazitaxel were hematologic; the rates (all
      grade) of neutropenia, leukopenia, and anemia were greater than 90%. Diarrhea,
      fatigue, asthenia, and back pain were the most common grade 3 or higher
      nonhematologic AEs. Because expected AEs from cabazitaxel therapy can delay or
      even interrupt treatment, oncology nurses need to be aware of those risks and
      their management. This article reviews the vital role of nurses in identifying
      patients at high risk for AEs associated with cabazitaxel therapy and reviews
      strategies for prevention and management of symptoms.

PMID- 22641323
TI  - Optimizing treatment outcomes in patients at risk for chemotherapy-induced nausea
      and vomiting.
AB  - Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial in
      maximizing patients' quality of life and optimizing outcomes of cancer therapy,
      and can be done more effectively than ever before. Appropriate antiemetic therapy
      combined with targeted patient education, clear communication, and management of
      patient expectations results in optimal emetogenic control. Oncology nurses play
      a critical role in the prevention and management of CINV. This column reviews the
      history and pathophysiology of treatments for CINV, as well as patient- and
      chemotherapy-specific risk factors that should be considered to optimize
      treatment outcomes in patients with CINV.

PMID- 22641322
TI  - Physical activity in patients with advanced-stage cancer: a systematic review of
      the literature.
AB  - The importance of physical activity for chronic disease prevention and management
      has become generally well accepted. The number of research interventions and
      publications examining the benefits of physical activity for patients with cancer
      has been rising steadily. However, much of that research has focused on the
      impact of physical activity either prior to or early in the cancer diagnosis,
      treatment, and survivorship process. Research focusing on the effects of physical
      activity, specifically for patients with advanced-stage cancer and poorer
      prognostic outcomes, has been addressed only recently. The purpose of this
      article is to examine the state of the science for physical activity in the
      advanced-stage disease subset of the cancer population. Exercise in a variety of
      intensities and forms, including yoga, walking, biking, and swimming, has many
      health benefits for people, including those diagnosed with cancer. Research has
      shown that, for people with cancer (including advanced-stage cancer), exercise
      can decrease anxiety, stress, and depression while improving levels of pain,
      fatigue, shortness of breath, constipation, and insomnia. People diagnosed with
      cancer should discuss with their oncologist safe, easy ways they can incorporate
      exercise into their daily lives.

PMID- 22641324
TI  - Breast cancer, panic disorder, and CYP2D6: a case study.
AB  - When patients with breast cancer also present with mental health issues, the
      psychiatric-mental health advanced practice RN is an appropriate provider for
      treatment and medication management. Collaboration with the oncology advanced
      practice nurse and the rest of the healthcare team can provide personalized,
      comprehensive care to this patient population. This article describes one
      example.

PMID- 22641325
TI  - Psychosocial concerns in cancer care: the role of the oncology nurse.
AB  - Oncology nurses know the importance of helping patients with cancer cope with
      their diagnosis and treatment. The impact of the disease and complex treatment
      regimens affects patients and families on many levels and often results in
      psychosocial concerns. The Oncology Nursing Society has been a national leader in
      advocating for complete care of patients with cancer, including the assessment of
      psychosocial concerns. New standards for accreditation of cancer facilities have
      brought national attention to this important element of cancer care.

PMID- 22641326
TI  - Nonpharmacologic interventions for breathlessness in advanced stages of malignant
      and nonmalignant diseases.

PMID- 22641327
TI  - Saving the best for last.

PMID- 22641328
TI  - Moving to wellness: a pilot study examining a nurse-driven exercise program in
      acutely ill patients with cancer.
AB  - Preventing patients with cancer from falling is a particularly important strategy
      for avoiding serious patient harm. Patients with cancer often fall as a result of
      overestimating their abilities as they adapt to the onset of fatigue and
      diminished functional status or muscle strength. That deconditioning can develop
      quickly with immobilization or prolonged recumbency. The effect of regularly
      supervised exercise programs led by nurses on maintaining muscle strength, thus
      preventing falls and reducing pressure ulcers, was examined in this feasibility
      study. Patients' muscle strength was assessed through the development and use of
      the Moving to Wellness Assessment Tool before implementing the Moving to Wellness
      Exercise Program. Of the 16 study participants, 81% maintained or improved their
      muscle strength compared to their original score. This pilot study was a unique
      opportunity to engage patients in a nurse-driven program to support minimal
      deconditioning of patients with cancer during acute illness.

PMID- 22641329
TI  - Implementation of national comprehensive cancer network evidence-based guidelines
      to prevent and treat cancer-related infections.
AB  - Clinical practice guidelines are an important result of evidence-based research.
      However, current clinical practice remains out of step with the rapid pace of
      research advancements. Often, decades pass before research is translated into
      clinical practice. The National Comprehensive Cancer Network (NCCN) has created
      evidence-based clinical guidelines to promote effective clinical practice.
      Formerly, the NCCN established guidelines to reduce cancer-related infections
      only for neutropenic patients; however, they have expanded their guidelines
      beyond neutropenia to prevent and treat cancer-related infections. Implementing
      scientific evidence into clinical practice is challenging and complex, and
      healthcare professionals should understand barriers to implementing clinical
      practice guidelines to ensure successful translation into practice. This article
      provides a brief review of NCCN guidelines and describes common barriers
      encountered during implementation. In addition, a conceptual framework is offered
      to help identify and address potential concerns before and after adoption of
      guidelines.

PMID- 22641330
TI  - Quality of life and mood state in Iranian women post mastectomy.
AB  - This study was conducted to examine mood state and quality of life (QOL) in
      patients who had undergone a mastectomy. The study used a descriptive design and
      was conducted in outpatient oncology clinics in northeastern Iran. Using the
      Profile of Mood States and the Ferrans and Powers Quality of Life Index, the mood
      state and QOL of patients who had undergone a mastectomy were examined. The
      results indicate that participants had low mood state and QOL; in addition, a
      negative correlation was found between the two. The mood state was a predictor of
      participants' QOL. A screening system for patients who have undergone a
      mastectomy may help nurses evaluate patients' mood states, identify the symptoms
      of mood disturbances, and refer patients to the appropriate support services.

PMID- 22641331
TI  - Gaining strength and focus from hardship.
AB  - Three members of my family have been diagnosed with cancer in the past five
      years. During the fall of my freshman year of high school, my older brother was
      diagnosed with acute lymphocytic leukemia. His health began to deteriorate in
      August 2006. My mother would take him to the hospital weekly, insisting that the
      doctors run every test on her ill-ridden son. Chris's diagnosis in November 2006
      accounted for his rapidly failing health and provided treatment options that
      would hopefully restore his once lively appearance and attitude. Now, five years
      after his diagnosis and less than a year from completion of treatment, I am able
      to call Chris's cancer a blessing. During his intensive and long protocol, my
      focus was on how unfair this diagnosis was. It was as if my eyes were shielded
      from anything positive and all I could see was darkness. Why my family? Why my
      brother? Why me? Is he going to die? These thoughts constantly pounded my brain,
      drawing me deeper into self-wallowing and pity. And, with each obstacle, whether
      it was a grand mal seizure, a near-deadly rash, or some other allergic reaction,
      I would dive deeper into this darker state. It took me a year to finally be able
      to say my brother has cancer without bursting into tears. And, within two years,
      I was beginning to feel alive again as I watched my brother gain strength with
      each new day.

PMID- 22641332
TI  - Integrating a cancer-specific geriatric assessment into survivorship care.
AB  - Older adults constitute the greatest percentage of cancer survivors in the
      country, with 61% being aged 65 years and older. Assessing older adult cancer
      survivors beyond chronological age to include changes in functional status is an
      essential process to help nurses anticipate cancer treatment impact and aid in
      planning individualized survivorship care. The objective of this article is to
      identify a method to assess older adult cancer survivors to be used in tailoring
      survivorship care. A review of geriatric literature was conducted through
      MEDLINE((r)) and PubMed from 1997-2011 and focused on the pathophysiology of
      aging, cancer impact, and comorbidities in this population. Results were combined
      with previous research to provide an evidence-based approach to assessing older
      cancer survivors. The resulting assessment provides valuable information on the
      functional status of older adult patients with cancer. This assessment can be
      used by nurses to develop treatment plans and tailor management strategies to
      improve quality of life.

PMID- 22641333
TI  - Social support and physical activity engagement by cancer survivors.
AB  - Less than 20% of adult cancer survivors participate in physical activity and, as
      a result of such inactivity, cancer survivors are at increased risk for
      developing chronic diseases. Studies have linked social support as a predictor of
      physical activity participation in healthy adults. The primary goal of this
      systematic review is to examine the relationship between social support and
      physical activity engagement in adult cancer survivors and determine whether
      additional research is needed in this area. Several databases were searched and
      articles were systematically extracted according to the inclusion and exclusion
      criteria. That search yielded 69 articles, 22 of which were identified and
      included in this review. Fifty percent of the studies showed a significant
      relationship between social support and physical activity engagement; however,
      59% of the participants were breast cancer survivors. The findings suggest that
      additional research is needed to develop social support strategies that will
      increase physical activity engagement in adult survivors of cancers other than
      breast cancer.

PMID- 22641334
TI  - The effects of hysterectomy on body image, self-esteem, and marital adjustment in
      Turkish women with gynecologic cancer.
AB  - The purpose of this research was to investigate the differences in the effect of
      hysterectomy on body image, self-esteem, and marital adjustment in Turkish women
      with gynecologic cancer based on specific independent variables, including age,
      education, employment, having or not having children, and income. This cross
      sectional study compared a group of women who underwent a hysterectomy (n = 100)
      with a healthy control group (n = 100). The study findings indicate that women
      who had a hysterectomy were found in worse conditions in terms of body image,
      self-esteem, and dyadic adjustment compared to healthy women. In terms of dyadic
      adjustment and body image among women who had undergone a hysterectomy, those
      with lower levels of income and education were found in poorer conditions. The
      study's findings show that hysterectomies have negative effects on body image,
      self-esteem, and dyadic adjustment in women affected by gynecologic cancer.
      Nursing assessment of self-esteem and marital adjustment indicators and
      implementation of strategies to increase self-confidence and self-esteem are
      needed for high-risk women.

PMID- 22641335
TI  - Prediction of "mostly dead" vs "all dead" after in-hospital cardiac arrest.

PMID- 22641336
TI  - Differentiation of fresh and frozen/thawed fish, European sea bass (Dicentrarchus
      labrax), gilthead seabream (Sparus aurata), cod (Gadus morhua) and salmon (Salmo
      salar), using volatile compounds by SPME/GC/MS.
AB  - BACKGROUND: A simple method based on solid phase microextraction/gas
      chromatography/mass spectrometry (SPME/GC/MS) was applied for studying the
      volatile profiles of whole fish samples of European sea bass (Dicentrarchus
      labrax) and gilthead seabream (Sparus aurata) and fillets of cod (Gadus morhua)
      and salmon (Salmo salar) during frozen storage in order to be able to
      differentiate a fresh product from one that has been frozen. Analysis of volatile
      compounds was performed on these two product types, fresh and after
      freezing/thawing following storage at - 20  degrees C for 30 and 90 days.
      RESULTS: More than a hundred volatile compounds were found by SPME/GC/MS.
      Statistical processing by principal component analysis and ascending hierarchical
      classification was used to classify the samples into categories and verify the
      possibility of separating fresh samples from those that had been frozen and
      thawed. The compounds to be used as differentiators were identified. Four
      compounds were common to all species: dimethyl sulfide, 3-methylbutanal, ethyl
      acetate and 2-methylbutanal. Not only were they found in larger quantities after
      thawing but they also increased with the duration of storage at - 20  degrees C.
      CONCLUSION: These four compounds can therefore be considered as potential markers
      of differentiation between a fresh product and one that has been frozen.

PMID- 22641337
TI  - Water extract of Hedyotis Diffusa Willd suppresses proliferation of human HepG2
      cells and potentiates the anticancer efficacy of low-dose 5-fluorouracil by
      inhibiting the CDK2-E2F1 pathway.
AB  - Hedyotis Diffusa Willd (HDW), a Chinese herbal medicine, has been widely used as
      an adjuvant therapy against various cancers, including hepatocellular carcinoma
      (HCC). However, the underlying anticancer mechanisms are yet to be elucidated. In
      the present study, the anticancer effects of HDW were evaluated and the efficacy
      and safety of HDW combined with low-dose 5-fluorouracil (5-FU) were investigated.
      HepG2 cells were cultured in vitro and nude mouse xenografts were established in
      vivo. The proliferation of HepG2 cells was measured using the MTT method and flow
      cytometry. The mRNA and protein expression levels of cyclin-dependent kinase 2
      (CDK2), cyclin E and E2F1 were examined using relative quantitative real-time PCR
      and western blot analysis, respectively. The results showed that water extract of
      HDW remarkably inhibited HepG2 cell proliferation in a dose-dependent manner via
      arrest of HepG2 cells at the G0/G1 phase and induction of S phase delay. This
      suppression was accompanied by a great decrease of E2F1 and CDK2 mRNA expression.
      In addition, HDW remarkably potentiated the anticancer effect of low-dose 5-FU in
      the absence of overt toxicity by downregulating the mRNA and protein levels of
      CDK2, cyclin E and E2F1. Our findings support the use of HDW as adjuvant therapy
      of chemotherapy and suggest that HDW may potentiate the efficiency of low-dose 5
      FU in treating HCC.

PMID- 22641338
TI  - The role of hepatic stellate cells in the regulation of T-cell function and the
      promotion of hepatocellular carcinoma.
AB  - Hepatic stellate cells (HSCs) have immunosuppressive abilities and may be
      responsible for the occurrence and development of hepatocellular carcinoma (HCC).
      However, the mechanisms through which HSCs affect T-cell-mediated immune
      responses remain unclear. The aim of this study was to elucidate these
      mechanisms. We examined the effect of HSCs on T-cell proliferation and apoptosis,
      regulatory T cells (Treg cells) and T-cell-mediated cytotoxicity using mixed
      leukocyte reactions (MLRs). Furthermore, we examined the cytokines present in the
      supernatant and the effect of this supernatant on the proliferation and migration
      of cancer cells. Finally, we examined the effect of HSCs on HCC cells in vivo. We
      found that activated HSCs induced T-cell hyporesponsiveness, accelerated
      activated T-cell apoptosis, increased the number of Treg cells and inhibited T
      cell-mediated cytotoxicity. HSCs also enhanced the expression of some cytokines
      and promoted the proliferation and migration of cancer cells. Furthermore,
      activated HSCs were able to induce HCC proliferation and Treg cells expansion in
      vivo. Activated HSCs may induce T cell anergy, thereby facilitating the
      immunologic escape of HCC cells.

PMID- 22641340
TI  - [The influence of cardiopulmonary bypass operation on the biodistribution of
      99mTc-HMPAO-labelled granulocytes - Evaluation in pigs by planar scintigraphy and
      section-analyses].
AB  - AIM: of the study was to evaluate the influence of an extra corporal perfusion
      (cardiopulmonary bypass operation - cpb) on activation and biodistribution of
      (99m)Tc labelled granulocytes in pigs with and without inhibition of the
      granulocytes by a leukocyte inhibition module (LIM). The cpb is often related to
      an activation of granulocytes resulting in an inflammatory answer. The biological
      mechanisms are unsolved yet. First trials of our group showed that LIM may
      inhibit the activation of neutrophils and therefore antagonize a cpb-caused
      impairment of cardiac function. This study is the continuation of these
      experiments with a higher number of animals and the focus on scintigraphic
      imaging. ANIMALS, MATERIAL, METHODS: 39 German landrace pigs were subdivided into
      three groups: group A (control) median sternotomy without cpb, group B with cpb,
      group C with LIM in addition to cpb. After labelling with (99m)Tc-HMPAO
      autologues granulocytes were reinjected. Subsequently to cpb, the animals
      underwent scintigraphic imaging. Quantification was performed with ROI evaluation
      and with tissue samples (section analysis) examined in a well counter. RESULTS: A
      high uptake of (99m)Tc-HMPAO was found in the liver. The count rates in brain,
      heart, lung, spleen and kidneys were far below. The amount of 99mTc-activity in
      the organ related to the half life corrected administered activity [%] was for
      the tissue samples (group A/B/C): brain 0.01/0.02/0.03; lung 12.1/8.3/11.5; heart
      0.35/0.54/0.42; kidney 1.24/0.87/1.02; spleen 4.0/4.0/4.5, liver 16.8/20.9/19.6.
      The count rates determined by ROI-evaluation of the scintigraphic images related
      to the total count rate in the image [%] were (group A/B/C): brain 1.1/0.9/1.0;
      lung 15.6/10.4/12.2; heart 4.0/3.5/3.4; kidney 4.0/2.9/3.2; spleen 7.6/7.7/9.5,
      liver 23.1/36.7/31.4. A significant difference in the tracer uptake between the
      groups could neither be detected by scintigraphic imaging nor evaluation of
      tissue samples. CONCLUSION: Scintigraphic imaging as well as section analysis
      showed a comparable biodistribution of the tracer. Therefore, the initial results
      of our group were not confirmed with a considerably higher number of animals.
      Neither cpb nor the use of the LIM influenced distribution of 99mTc-labelled
      granulocytes in pigs significantly.

PMID- 22641339
TI  - Optimal ablation strategies for different types of ventricular tachycardias.
AB  - Ablation strategies for almost all types of ventricular tachycardias have now
      been established. The optimal ablation strategy for ventricular tachycardia is
      determined by the site of origin and the electrophysiological mechanisms.
      Electrocardiograms, an understanding of the common sites of basic disease, and
      identification of the scar site using imaging modalities might be helpful for
      predicting the originating location. Electrophysiological activation mapping is
      the gold standard for identification of the ventricular tachycardia substrate.
      However, when activation mapping of scar-related ventricular tachycardias is not
      possible, substrate mapping might be performed to identify isolated diastolic
      potentials. Substrates are commonly located in the endocardium, but transvenous
      or subxiphoidal intrapericardial approaches can be used to map epicardial
      substrates. Unusual types of ventricular tachycardia might require special
      strategies, such as transcoronary ethanol or intramural needle ablation. For
      idiopathic ventricular tachycardias, ablation might be a first-line therapy
      because of its high efficacy and very low risk of complications. However, the
      recurrence rate of scar-related ventricular tachycardias remains considerable,
      and ablation remains an adjunctive therapy to medical therapy and implantable
      cardioverter-defibrillators. When incessant ventricular tachycardia or
      fibrillation requiring defibrillator therapy (electrical storm) is refractory to
      antiarrhythmic drugs, neuraxial modulation, including sedation, might be the next
      option before catheter ablation is attempted.

PMID- 22641341
TI  - [Perception accuracy of BRCA1/2 mutation predisposition in breast cancer women
      and associated factors].
AB  - This study aims to determine accuracy between perceived risk of genetic
      predisposition and objective estimation of this risk, and its associated factors
      in women, probands affected with breast cancer. Perception of this risk, absolute
      and comparative, was confronted with objective estimation. Emotional distress and
      knowledge postcounseling were measured, respectively by the Hospital Anxiety and
      Depression Scale (HADS), Impact of Event Scale (IES) and the Breast Genetic
      Counseling Knowledge Questionnaire (BGKQ). On 213 eligible consultants, the 173
      questionnaires (81.2%) analyzed revealed an inaccuracy of perception of absolute
      and comparative risks in 50 and 55.3%, respectively. An unsignificant tendency to
      overestimate the absolute risk (p = 0,08) and a significant underestimation of
      comparative risk (p < 0.001) appear. The inaccuracy of the perception of absolute
      risk is associated with greater distress (beta = 0.150) and a lower educational
      level (beta = -0.164), while the comparative risk is associated with higher
      knowledge (beta = 0.208), higher level of education (beta = 0.176) and a younger
      age (beta = -0.151). Living in couple is a factor of inaccuracy of both form of
      risk assessment (beta = 0.189, beta = 0.147). While the adequacy of the perceived
      risk of carrying a mutation in a BRCA1 /2 should promote an informed decision
      about genetic testing and anticipation of its outcome, a large number of
      consultants does not apprehend this risk correctly when they have emotional
      distress and despite knowledge of the risk of breast cancer.

PMID- 22641342
TI  - Graca Raposo: melanosomes, more than skin deep. Interviewed by Caitlin Sedwick.

PMID- 22641343
TI  - Tracing epithelial stem cells during development, homeostasis, and repair.
AB  - Epithelia ensure many critical functions of the body, including protection
      against the external environment, nutrition, respiration, and reproduction. Stem
      cells (SCs) located in the various epithelia ensure the homeostasis and repair of
      these tissues throughout the lifetime of the animal. Genetic lineage tracing in
      mice has allowed the labeling of SCs and their progeny. This technique has been
      instrumental in characterizing the origin and heterogeneity of epithelial SCs,
      their tissue location, and their differentiation potential under physiological
      conditions and during tissue regeneration.

PMID- 22641344
TI  - Talin activates integrins by altering the topology of the beta transmembrane
      domain.
AB  - Talin binding to integrin beta tails increases ligand binding affinity
      (activation). Changes in beta transmembrane domain (TMD) topology that disrupt
      alpha-beta TMD interactions are proposed to mediate integrin activation. In this
      paper, we used membrane-embedded integrin beta3 TMDs bearing environmentally
      sensitive fluorophores at inner or outer membrane water interfaces to monitor
      talin-induced beta3 TMD motion in model membranes. Talin binding to the beta3
      cytoplasmic domain increased amino acid side chain embedding at the inner and
      outer borders of the beta3 TMD, indicating altered topology of the beta3 TMD.
      Talin's capacity to effect this change depended on its ability to bind to both
      the integrin beta tail and the membrane. Introduction of a flexible hinge at the
      midpoint of the beta3 TMD decoupled the talin-induced change in intracellular TMD
      topology from the extracellular side and blocked talin-induced activation of
      integrin alphaIIbbeta3. Thus, we show that talin binding to the integrin beta TMD
      alters the topology of the TMD, resulting in integrin activation.

PMID- 22641345
TI  - Nucleostemin prevents telomere damage by promoting PML-IV recruitment to
      SUMOylated TRF1.
AB  - Continuously dividing cells must be protected from telomeric and nontelomeric DNA
      damage in order to maintain their proliferative potential. Here, we report a
      novel telomere-protecting mechanism regulated by nucleostemin (NS). NS depletion
      increased the number of telomere damage foci in both telomerase-active (TA(+))
      and alternative lengthening of telomere (ALT) cells and decreased the percentage
      of damaged telomeres associated with ALT-associated PML bodies (APB) and the
      number of APB in ALT cells. Mechanistically, NS could promote the recruitment of
      PML-IV to SUMOylated TRF1 in TA(+) and ALT cells. This event was stimulated by
      DNA damage. Supporting the importance of NS and PML-IV in telomere protection, we
      demonstrate that loss of NS or PML-IV increased the frequency of telomere damage
      and aberration, reduced telomeric length, and perturbed the TRF2(DeltaBDeltaM)
      induced telomeric recruitment of RAD51. Conversely, overexpression of either NS
      or PML-IV protected ALT and TA(+) cells from telomere damage. This work reveals a
      novel mechanism in telomere protection.

PMID- 22641347
TI  - Mechanically and structurally robust sulfonated block copolymer membranes for
      water purification applications.
AB  - The effective removal of ionic pollutants from contaminated water using
      negatively charged nanofiltration membranes is demonstrated. Block copolymers
      comprising polystyrene (PS) and partially hydrogenated polyisoprene (hPI) were
      synthesized by varying chain architectures. A one step procedure of cross-linking
      (hPI blocks) and sulfonation reactions (PS chains) was then carried out, which
      was revealed as an effective method to enhance mechanical integrity of membranes
      while hydrophilic sulfonated chains remain intact. In particular, the control of
      chain architecture allows us to create a synergetic effect on optimizing charge
      densities of the membrane, water permeability, and mechanical integrity under
      water purification conditions. The best performing membrane can almost completely
      (>99%) reject various divalent cations and also show NO(3)(-) rejection > 85% and
      Na(+) rejection > 87%. Well defined nanostructures (tens of nanometers) as well
      as the periodically arranged water domains (a few nanometers) within hydrophilic
      phases of the hydrated membranes were confirmed by in situ neutron scattering
      experiments.

PMID- 22641348
TI  - Porous gold nanodisks with multiple internal hot spots.
AB  - For increasing the number of internal hot spots in the individual plasmonic
      nanoparticles, porous Au nanostructures were synthesized by a hybrid approach
      combining a physical process, which defined the overall shapes and dimensions of
      the nanostructures, and a chemical process, which incorporated nanopores inside
      the patterned nanostructures. This approach allows us to synthesize
      lithographically designed Au nanodisks containing numerous internal Raman hot
      spots in the form of nanopores. The increased number of hot spots successfully
      improved SERS intensity, and this experimental result was further elucidated by
      numerical electromagnetic simulations. The highly improved and homogeneous SERS
      intensities illustrate the great potential of the porous plasmonic nanodisks as a
      sensitive molecular imaging agent.

PMID- 22641346
TI  - LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian
      mitotic progression.
AB  - In the mitotic exit network of budding yeast, Dbf2 kinase phosphorylates and
      regulates Cdc14 phosphatase. In contrast, no phosphatase substrates of
      LATS1/WARTS kinase, the mammalian equivalent of Dbf2, has been reported. To
      address this discrepancy, we performed phosphoproteomic screening using LATS1
      kinase. Screening identified MYPT1 (myosin phosphatase-targeting subunit 1) as a
      new substrate for LATS1. LATS1 directly and preferentially phosphorylated serine
      445 (S445) of MYPT1. An MYPT1 mutant (S445A) failed to dephosphorylate Thr 210 of
      PLK1 (pololike kinase 1), thereby activating PLK1. This suggests that LATS1
      promotes MYPT1 to antagonize PLK1 activity. Consistent with this, LATS1-depleted
      HeLa cells or fibroblasts from LATS1 knockout mice showed increased PLK1
      activity. We also found deoxyribonucleic acid (DNA) damage-induced LATS1
      activation caused PLK1 suppression via the phosphorylation of MYPT1 S445.
      Furthermore, LATS1 knockdown cells showed reduced G2 checkpoint arrest after DNA
      damage. These results indicate that LATS1 phosphorylates a phosphatase as does
      the yeast Dbf2 and demonstrate a novel role of LATS1 in controlling PLK1 at the
      G2 DNA damage checkpoint.

PMID- 22641349
TI  - Low incidence of adenovirus hemorrhagic cystitis following autologous
      hematopoietic stem cell transplantation in the rituximab era.

PMID- 22641350
TI  - Differential occurrence of S100A7 in breast cancer tissues: a proteomic-based
      investigation.
AB  - PURPOSE: The present study reports for the first time a large-scale proteomic
      screening of the occurrence, subcellular localization and relative quantification
      of the S100A7 protein among a group of 100 patients, clinically grouped for the
      diagnosis of infiltrating ductal carcinoma (IDC). EXPERIMENTAL DESIGN: To this
      purpose, the methods of differential proteomics, Western blotting, and
      immunohistochemistry were used. RESULTS: The identity of two isoforms of the
      protein was assessed by mass spectrometry and immunologically confirmed.
      Moreover, we proved by immunocytochemical applications the exclusive localization
      of the protein within the neoplastic cells. The correlation of S100A7 expression
      levels with the collective profile of cancer patients' proteomics predicted
      functional interactions, distinct for the two isoforms. The S100A7b isoform was
      significantly correlated with specific protein clusters (calcium binding,
      signaling and cell motion, heat shock and folding) and intercrossing pathways
      (antioxidant, metabolic and apoptotic pathways), while the more acidic isoform
      was correlated with a narrow number of proteins mainly unrelated to the b
      isoform. CONCLUSIONS AND CLINICAL RELEVANCE: This study is the first proteomic
      based report on S100A7 in a large series of IDC patients. The correlation with in
      silico data may significantly contribute the knowledge of possible pathways for
      S100A7, providing novel insights into the mechanism of action of this protein. We
      suggest that each S100A7 isoform is involved in critical phases of the breast
      cancer growth and progression, probably through interaction with different
      partner proteins.

PMID- 22641351
TI  - Ferroelectric tunnel junction memory devices made from monolayers of vinylidene
      fluoride oligomers.

PMID- 22641352
TI  - Designed synthetic analogs of the alpha-helical peptide temporin-La with improved
      antitumor efficacies via charge modification and incorporation of the integrin
      alphavbeta3 homing domain.
AB  - How to target cancer cells with high specificity and kill cancer cells with high
      efficiency remains an urgent demand for anticancer drugs. Temporin-La, which
      belongs to the family of temporins, presents antitumor activity against many
      cancer cell lines. We first used a whole bioinformatic analysis method as a
      platform to identify new anticancer antimicrobial peptides (AMPs). On the basis
      of these results, we designed a temporin-La analog (temporin-Las) and related
      constructs containing the Arg-Gly-Asp (RGD) tripeptide, the integrin alphavbeta3
      homing domain (RGD-La and RGD-Las). We detected a link between the net charges
      and integrin alphavbeta3 expression of cancer cell lines and the antitumor
      activities of these peptides. Temporin-La and its synthetic analogs inhibited
      cancer cell proliferation in a dose-dependent manner. Evidence was provided that
      the affinity between RGD-Las and tumor cell membranes was stronger than other
      tested peptides using a pull-down assay. Morphological changes on the cell
      membrane induced by temporin-La and RDG-Las, respectively, were examined by
      scanning electron microscopy. Additionally, time-dependent morphological changes
      were detected by confocal microscopy, where the binding process of RGD-Las to the
      cell membrane could be monitored. The results indicate that the electrostatic
      interaction between these cationic peptides and the anionic cell membrane is a
      major determinant of selective cell killing. Thus, the RGD tripeptide is a
      valuable ligand motif for tumor targeting, which leads to an increased anticancer
      efficiency by RGD-Las. These AMP-derived peptides have clinical potential as
      specifically targeting agents for the treatment of alphavbeta3 positive tumors.

PMID- 22641357
TI  - Type II enteropathy-associated T-cell lymphoma: a multicenter analysis from the
      Asia Lymphoma Study Group.
AB  - Enteropathy-associated T-cell lymphoma (EATL) is a rare primary gastrointestinal
      T-cell lymphoma. A multicenter study from the Asia Lymphoma Study Group
      identified 38 EATL patients within a 19-year period. All cases were type II EATL.
      Men were affected twice as common as women, at a median age of 59 (23-89) years.
      None had a history of celiac disease. The sites of involvement were small bowel
      and stomach (5%), small bowel (63%), small and large bowel (16%), and large bowel
      (18%). Common presenting features were bowel perforation (34%), pain (32%), and
      obstruction (21%). Lymphomas showed monomorphic neoplastic lymphoid infiltrates
      that were CD3+ (100%), CD56+ (91%), TIA-1+ (96%), CD4-CD8+ (63%), CD4+CD8+ (19%),
      CD4-CD8- (16%), and CD4+CD8- (3%). Epstein Barr virus was demonstrable in three
      cases. Despite chemotherapy and/or surgical resection, the overall response and
      complete response rates were poor at 46% and 38%. The median overall survival
      (OS) was 7 months and progression-free-survival (PFS) 1 month. Five patients
      underwent hematopoietic stem cell transplantation all were alive. Age and the
      prognostic index for peripheral T-cell lymphoma were not prognostically
      significant. Good performance status was associated with better OS (P = 0.03),
      and response to initial treatment led to better OS and PFS (P < 0.001).

PMID- 22641358
TI  - Combined administration of EGCG and IL-1 receptor antagonist efficiently
      downregulates IL-1-induced tumorigenic factors in U-2 OS human osteosarcoma
      cells.
AB  - Chronic inflammation represents one of the hallmarks of cancer. Of special
      relevance to the malignant process is the pro-inflammatory cytokine IL-1 playing
      a crucial role in cancer-related inflammation. Recent observations indicate
      increased IL-1 levels in an animal model of human osteosarcoma, the most frequent
      primary malignant bone tumor in man. In patients with bone sarcomas, increased
      serum levels of tumor-promoting cytokines, including IL-6, IL-8 and VEGF can be
      found, correlating with poor overall survival. The link between cancer and
      inflammation makes it clear that there is a need to reduce the external factors
      inducing inflammation as a preventive or therapeutical measure. Therefore, in the
      present study the effects of anti-inflammatory IL-1 receptor antagonist (IL-1Ra)
      was tested alone and in combination with (-)-epigallocatechin-3-gallate (EGCG),
      an anti-inflammatory chemopreventive agent from green tea, on the production of
      IL-1-induced tumorigenic factors in U-2 OS human osteosarcoma cells. We found
      that IL-1Ra and EGCG downregulated IL-1-induced IL-6 and IL-8 release from U-2 OS
      cells by 65-85%. IL-1Ra and EGCG also reduced secretion of invasiveness-promoting
      MMP-2 and pro-angiogenic VEGF to 62-75% without affecting the metabolic response
      and caspase-3 activity. In conclusion, downregulation of IL-1-induced tumorigenic
      factors (IL-6, IL-8, VEGF, MMP-2) in U-2 OS by IL-1Ra and EGCG may positively
      affect tumor-associated inflammation and, as a consequence, lead to reduction in
      angiogenesis and invasiveness. This renders a combined administration of EGCG and
      IL-1Ra a promising approach as an adjuvant therapy in patients with osteosarcoma.

PMID- 22641359
TI  - Characterization of giant marker and ring chromosomes in a pleomorphic
      leiomyosarcoma of soft tissue by spectral karyotyping.
AB  - Pleomorphic leiomyosarcoma of soft tissue is relatively rare and its cytogenetic
      and molecular genetic data are scarce. We present a case of pleomorphic
      leiomyosarcoma arising in the left thigh of a 60-year-old man. Fluorine-18
      deoxyglucose positron emission tomography imaging showed a homogenously high
      uptake within the mass in the proximal left thigh (maximum standardized uptake
      value, 20.9). Following a core needle biopsy, wide resection of the tumor was
      performed. Histologically, the tumor was composed of a mixture of spindle cells,
      polygonal cells and bizarre giant cells forming interlacing bundles and a
      storiform pattern. Immunohistochemically, the tumor cells were positive for
      vimentin, smooth muscle actin and desmin. The MIB-1 labeling index was 19.7% in
      the highest spot. Cytogenetic analysis exhibited a complex karyotype with several
      numerical and structural alterations, including giant marker and ring
      chromosomes. Spectral karyotyping demonstrated that giant marker and ring
      chromosomes were composed of material from the X chromosome. Metaphase-based
      comparative genomic hybridization analysis showed high-level amplifications of
      1q21-q25 and 12q13-q21 and gains of 1p31-p32, 10p11-p13, 17p11 and 19p13. The
      patient received postoperative adjuvant radiotherapy and doxorubicin-based
      chemotherapy. No local recurrence or distant metastasis was detected during a
      follow-up period of 19 months. The clinicopathological, cytogenetic and molecular
      genetic features of pleomorphic soft tissue leiomyosarcoma are discussed.

PMID- 22641360
TI  - Urological cancer: Chemoradiation superior in muscle-invasive bladder cancer.

PMID- 22641362
TI  - Clinical trials: New options for melanoma?

PMID- 22641361
TI  - Translational approaches to treatment-induced symptoms in cancer patients.
AB  - Cancer therapy makes patients sick. The therapies that are available to
      clinicians allow them to successfully control nausea, emesis and pain. However,
      this is not the case for a number of other symptoms that include fatigue,
      distractibility, poor memory, and diminished interest in previously pleasurable
      activities. These symptoms cluster during the course of cancer therapy and impair
      patient quality of life, limit therapy options and do not always resolve at the
      cessation of treatment. It is possible to describe the intensity and temporal
      features of symptoms and assess their relationship with the inflammatory response
      that is associated with cancer and cancer therapy. At the preclinical level,
      sophisticated animal models still need to be deployed to study the causal role of
      inflammation in specific components of cancer-related symptoms. Various
      approaches can be optimally combined in a translational symptom research pathway
      to provide a framework for assessing in a systematic manner the neurobehavioral
      toxicity of existing and newly developed cancer therapies. Ultimately, this
      knowledge will allow derivation of mechanism-based interventions to prevent or
      alleviate cancer-related symptoms.

PMID- 22641363
TI  - Urological cancer: Genetic landscape studies of prostate cancer offer new clues.

PMID- 22641365
TI  - Basic research: A close look at PARP-1.

PMID- 22641366
TI  - Breast cancer: Whole is better than the part.

PMID- 22641364
TI  - Paediatric and adult malignant glioma: close relatives or distant cousins?
AB  - Gliomas in children differ from their adult counterparts by their distribution of
      histological grade, site of presentation and rate of malignant transformation.
      Although rare in the paediatric population, patients with high-grade gliomas
      have, for the most part, a comparably dismal clinical outcome to older patients
      with morphologically similar lesions. Molecular profiling data have begun to
      reveal the major genetic alterations underpinning these malignant tumours in
      children. Indeed, the accumulation of large datasets on adult high-grade glioma
      has revealed key biological differences between the adult and paediatric disease.
      Furthermore, subclassifications within the childhood age group can be made
      depending on age at diagnosis and tumour site. However, challenges remain on how
      to reconcile clinical data from adult patients to tailor novel treatment
      strategies specifically for paediatric patients.

PMID- 22641367
TI  - Failure event types and prognostic factors after node-positive breast cancer in
      patients treated by adjuvant chemotherapy: impact on follow-up.
AB  - PURPOSE: The role of post-therapeutic follow-up for breast cancer patients (pts)
      is open to debate. The aim of this study was to identify prognostic factors
      associated with the type of first event. METHODS: Data of 2,820 pts included in
      three adjuvant trials for node-positive breast cancer were used. Competing risk
      methodology was used to identify prognostic factors associated with time to first
      failure according to type of event. RESULTS: After a median follow-up of 53
      months, 732 pts had disease-related events (114 locoregional, 58 contralateral,
      and 560 distant metastasis). The prognostic factors associated with high
      locoregional recurrence were young age, number of positive lymph nodes and grade
      III. In multivariate analysis, the type of first event influenced post-relapse
      survival. Nottingham Prognostic Index identified three groups of pts at different
      risk of relapse. CONCLUSION: Early relapse is rare in the first year after
      surgery and is associated with more aggressive disease. Using the Nottingham
      Prognostic Index, it is possible to identify pts at lower risks of relapse for
      whom it seems reasonable to limit the frequency of routine follow-up during the
      first years. For pts at higher risk of locoregional recurrence, regular follow-up
      should be maintained in order to detect potential curative events.

PMID- 22641369
TI  - Simplified platelet sample preparation for SDS-PAGE-based proteomic studies.
AB  - PURPOSE: The goal of this study was to design an easy and simple protocol for
      platelet isolation and sample preparation for proteomic studies based on 2DE (IEF
      SDS-PAGE) followed by Coomassie blue staining. EXPERIMENTAL DESIGN: Blood was
      collected by venipuncture into tubes coated with EDTA and platelet-rich plasma
      (PRP) was immediately obtained by centrifugation. PRP was stored refrigerated in
      closed Falcon tubes for 0, 1, 2, 3, 5, and 7 days and platelets were isolated by
      centrifugation. 2DE gels were stained with colloidal Coomassie blue stain and
      evaluated using the Progenesis SameSpots software. Spots that differed
      significantly in the gels of fresh and stored platelet samples were excised,
      digested with trypsin, and further analyzed using nanoLC-MS/MS. RESULTS: During
      the 7-day follow-up period, we found 20 spots that differed significantly (ANOVA
      p <0.05). During the first 2 days of PRP storage in test tubes, however, only
      nine spots significantly differed in all donors. In these spots, we identified 14
      different proteins. CONCLUSIONS AND CLINICAL RELEVANCE: In conclusion, for
      proteome investigations, whenever it is not feasible to prepare washed platelets
      immediately after blood collection, the EDTA-anticoagulated PRP can be stored in
      test tubes at 4 degrees C for up to 2 days for the platelet proteome
      investigation.

PMID- 22641368
TI  - MicroRNA profiling of carcinogen-induced rat colon tumors and the influence of
      dietary spinach.
AB  - SCOPE: MicroRNA (miRNA) profiles are altered in chronic conditions such as
      cardiovascular disease, diabetes, neurological disorders, and cancer. A systems
      biology approach was used to examine, for the first time, miRNAs altered in rat
      colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a
      heterocyclic amine carcinogen from cooked meat. METHODS AND RESULTS: Among the
      most highly dysregulated miRNAs were those belonging to the let-7 family.
      Subsequent computational modeling and target validation identified c-Myc and
      miRNA-binding proteins Lin28A/Lin28B (Lin28) as key players, along with Sox2,
      Nanog, and Oct-3/4. These targets of altered miRNAs in colon cancers have been
      implicated in tumor recurrence and reduced patient survival, in addition to their
      role as pluripotency factors. In parallel with these findings, the tumor
      suppressive effects of dietary spinach given postinitiation correlated with
      elevated levels of let-7 family members and partial normalization of c-myc, Sox2,
      Nanog, Oct-3/4, HmgA2, Dnmt3b, and P53 expression. CONCLUSION: We conclude that
      the let-7/c-Myc/Lin28 axis is dysregulated in heterocyclic amine-induced colon
      carcinogenesis, and that the tumor suppressive effects of dietary spinach are
      associated with partial normalization of this pathway.

PMID- 22641370
TI  - Chemical stabilization of gold coated by silver core-shell nanoparticles via
      electron transfer.
AB  - Silver nanoparticles are notoriously susceptible to oxidation, yet gold
      nanoparticles coated in silver exhibit a unique electronic interaction that
      occurs at the interface of the two metals, leading to enhanced stability
      properties for the silver shell. In order to probe the phenomenon, the stability
      of gold nanoparticles coated by silver was studied in the presence of various
      chloride-containing electrolytes. It was found that a critical silver shell
      thickness of approximately 1 nm exists that cannot be oxidatively etched from the
      particle surface: this is in contrast to the observation of complete oxidative
      etching for monometallic silver nanoparticles. The results are discussed in terms
      of particle composition, structure and morphology before and after exposing the
      particles to the electrolytes. Raman analysis of the reporter molecule 3-amino
      1,2,4-triazole-5-thiol adsorbed on the particle surface illustrates the
      feasibility of using gold coated by silver nanoparticle probes in sensing
      applications that require the presence of high levels of salt. The results
      provide insight into the manipulation of the electronic and stability properties
      for gold- and silver-based nanoparticles.

PMID- 22641371
TI  - PABPN1 shuts down alternative poly(A) sites.
AB  - Although overlooked for many years, alternative cleavage and polyadenylation
      (APA) is now emerging as a major mechanism of gene regulation. A recent study
      identifies poly(A)-binding protein nuclear 1 (PABPN1), a general factor of
      polyadenylation, as a suppressor of alternative poly(A) sites.

PMID- 22641372
TI  - Gametogenesis in a dish.
AB  - Recent progress in the induced pluripotent stem cell (iPSC) field as well as the
      establishment of germline stem cell isolation and culture methodologies may
      provide an in vitro platform for the study of physiological and pathological
      human gamete development and open new avenues for cell replacement-based
      personalized treatment of infertility.

PMID- 22641373
TI  - Found in translation of mTOR signaling.
AB  - The mammalian target of rapamycin (mTOR) protein kinase regulates a wide variety
      of cellular processes, including protein synthesis, yet the downstream
      translational program under the control of mTOR is poorly understood. Two recent
      studies by Hsieh et al. and Thoreen et al. now start to address this issue, and
      uncover a subset of genes translationally regulated by oncogenic mTOR signaling
      that may contribute to tumorigenesis.

PMID- 22641375
TI  - alpha-Oligofurans show a sizeable extent of pi-conjugation as probed by Raman
      spectroscopy.
AB  - A Raman spectroscopic analysis revealed that pi-conjugation does not reach
      saturation at least up to the octamer in long alpha-oligofurans and spreads over
      14-15 furan units in the polyfuran. Comparing DFT calculations with experimental
      results suggests that a considerable amount of HF exchange is required to
      reproduce computationally the observed conjugation.

PMID- 22641374
TI  - Clinical course of non-specific low back pain: a systematic review of prospective
      cohort studies set in primary care.
AB  - BACKGROUND AND OBJECTIVE: Non-specific low back pain is a relatively common and
      recurrent condition for which at present there is no effective cure. In current
      guidelines, the prognosis of acute non-specific back pain is assumed to be
      favourable, but this assumption is mainly based on return to function. This
      systematic review investigates the clinical course of pain in patients with non
      specific acute low back pain who seek treatment in primary care. DATABASES AND
      DATA TREATMENT: Included were prospective studies, with follow-up of at least 12
      months, that studied the prognosis of patients with low back pain for less than 3
      months of duration in primary care settings. Proportions of patients still
      reporting pain during follow-up were pooled using a random-effects model.
      Subgroup analyses were used to identify sources of variation between the results
      of individual studies. RESULTS: A total of 11 studies were eligible for
      evaluation. In the first 3 months, recovery is observed in 33% of patients, but 1
      year after onset, 65% still report pain. Subgroup analysis reveals that the
      pooled proportion of patients still reporting pain after 1 year was 71% at 12
      months for studies that considered total absence of pain as a criterion for
      recovery versus 57% for studies that used a less stringent definition. The pooled
      proportion for Australian studies was 41% versus 69% for European or US studies.
      CONCLUSIONS: The findings of this review indicate that the assumption that
      spontaneous recovery occurs in a large majority of patients is not justified.
      There should be more focus on intensive follow-up of patients who have not
      recovered within the first 3 months.

PMID- 22641376
TI  - [Give me a fixed point in space, and I will lift the world upside down].

PMID- 22641377
TI  - Hypoplastic presentation of acute lymphoblastic leukemia.

PMID- 22641378
TI  - Improving the specificity of the PF4 ELISA in diagnosing heparin-induced
      thrombocytopenia.
AB  - Heparin induced thrombocytopenia (HIT) is a serious complication of heparin
      therapy. The PF4 ELISA is a serologic assay that provides laboratory support for
      the clinical diagnosis of HIT, but it is often positive in patients who do not
      have the syndrome. We examined whether the specificity of the PF4 ELISA can be
      improved by 1) taking antibody potency into consideration, 2) by measuring only
      IgG antibodies, and 3) by utilizing a high concentration heparin inhibition step.
      We reviewed clinical information on 116 patients whose samples were referred for
      HIT antibody testing and assigned each a clinical score related to the likelihood
      of the patient having HIT. The scores were then correlated with serologic
      findings. Patients with strongly positive PF4ELISA results (OD >= 1.0) using both
      versions of the assay (IgG/A/M and IgG only) had clinical scores and SRA activity
      that were significantly higher than those having reactive or negative results.
      When the IgG-only PF4 ELISA was used, only the strongly positive result group had
      significantly higher clinical scores and SRA release, and fewer samples were
      classified as weakly positive or reactive, suggesting that detection of IgG only
      in the PF4 ELISA improves the assay's specificity. The heparin inhibition step
      identified "reactive" samples that were associated with clinical scores and SRA
      release indistinguishable from the "negative" result groups, confirming that this
      step further improves specificity of the test. This study supports utilizing
      these 3 modifications of the PF4 ELISA to improve specificity in supporting the
      clinical diagnosis of HIT.

PMID- 22641379
TI  - Magnetic and optical bistability in tetrairon(III) single molecule magnets
      functionalized with azobenzene groups.
AB  - Tetrairon(III) complexes known as "ferric stars" have been functionalized with
      azobenzene groups to investigate the effect of light-induced trans-cis
      isomerization on single-molecule magnet (SMM) behaviour. According to DC magnetic
      data and EPR spectroscopy, clusters dispersed in polystyrene (4% w/w) exhibit the
      same spin (S = 5) and magnetic anisotropy as bulk samples. Ligand
      photoisomerization, achieved by irradiation at 365 nm, has no detectable
      influence on static magnetic properties. However, it induces a small but
      significant acceleration of magnetic relaxation as probed by AC susceptometry.
      The pristine behaviour can be almost quantitatively recovered by irradiation with
      white light. Our studies demonstrate that magnetic and optical bistability can be
      made to coexist in SMM materials, which are of current interest in molecular
      spintronics.

PMID- 22641381
TI  - Analog modeling of Worm-Like Chain molecules using macroscopic beads-on-a-string.
AB  - This paper describes an empirical model of polymer dynamics, based on the
      agitation of millimeter-sized polymeric beads. Although the interactions between
      the particles in the macroscopic model and those between the monomers of
      molecular-scale polymers are fundamentally different, both systems follow the
      Worm-Like Chain theory.

PMID- 22641382
TI  - Potent and broad neutralization of HIV-1 by a llama antibody elicited by
      immunization.
AB  - Llamas (Lama glama) naturally produce heavy chain-only antibodies (Abs) in
      addition to conventional Abs. The variable regions (VHH) in these heavy chain
      only Abs demonstrate comparable affinity and specificity for antigens to
      conventional immunoglobulins despite their much smaller size. To date,
      immunizations in humans and animal models have yielded only Abs with limited
      ability to neutralize HIV-1. In this study, a VHH phagemid library generated from
      a llama that was multiply immunized with recombinant trimeric HIV-1 envelope
      proteins (Envs) was screened directly for HIV-1 neutralization. One VHH, L8CJ3
      (J3), neutralized 96 of 100 tested HIV-1 strains, encompassing subtypes A, B, C,
      D, BC, AE, AG, AC, ACD, CD, and G. J3 also potently neutralized chimeric simian
      HIV strains with HIV subtypes B and C Env. The sequence of J3 is highly divergent
      from previous anti-HIV-1 VHH and its own germline sequence. J3 achieves broad and
      potent neutralization of HIV-1 via interaction with the CD4-binding site of HIV-1
      Env. This study may represent a new benchmark for immunogens to be included in B
      cell-based vaccines and supports the development of VHH as anti-HIV-1
      microbicides.

PMID- 22641380
TI  - Engineering nano- and microparticles to tune immunity.
AB  - The immune system can be a cure or cause of disease, fulfilling a protective role
      in attacking cancer or pathogenic microbes but also causing tissue destruction in
      autoimmune disorders. Thus, therapies aimed to amplify or suppress immune
      reactions are of great interest. However, the complex regulation of the immune
      system, coupled with the potential systemic side effects associated with
      traditional systemic drug therapies, has presented a major hurdle for the
      development of successful immunotherapies. Recent progress in the design of
      synthetic micro- and nano-particles that can target drugs, deliver imaging
      agents, or stimulate immune cells directly through their physical and chemical
      properties is leading to new approaches to deliver vaccines, promote immune
      responses against tumors, and suppress autoimmunity. In addition, novel
      strategies, such as the use of particle-laden immune cells as living targeting
      agents for drugs, are providing exciting new approaches for immunotherapy. This
      progress report describes recent advances in the design of micro- and nano
      particles for immunotherapies and diagnostics.

PMID- 22641383
TI  - Programmed cell death 1 forms negative costimulatory microclusters that directly
      inhibit T cell receptor signaling by recruiting phosphatase SHP2.
AB  - Programmed cell death 1 (PD-1) is a negative costimulatory receptor critical for
      the suppression of T cell activation in vitro and in vivo. Single cell imaging
      elucidated a molecular mechanism of PD-1-mediated suppression. PD-1 becomes
      clustered with T cell receptors (TCRs) upon binding to its ligand PD-L1 and is
      transiently associated with the phosphatase SHP2 (Src homology 2 domain
      containing tyrosine phosphatase 2). These negative costimulatory microclusters
      induce the dephosphorylation of the proximal TCR signaling molecules. This
      results in the suppression of T cell activation and blockade of the TCR-induced
      stop signal. In addition to PD-1 clustering, PD-1-TCR colocalization within
      microclusters is required for efficient PD-1-mediated suppression. This
      inhibitory mechanism also functions in PD-1(hi) T cells generated in vivo and can
      be overridden by a neutralizing anti-PD-L1 antibody. Therefore, PD-1 microcluster
      formation is important for regulation of T cell activation.

PMID- 22641384
TI  - Adenovirus-mediated tissue-targeted expression of the CDglyTk gene for the
      treatment of breast cancer.
AB  - The aim of this study was to evaluate the selective killing efficacy of
      adenovirus (Ad)-mediated double suicide genes driven by the kinase domain
      containing receptor (KDR) promoter in human breast cancer cells and vascular
      endothelial cells. Two Ad-mediated double suicide gene systems [with the two
      suicide genes, thymidine kinase (TK) and cytosine deaminase (CD)] with the KDR
      promoter (Ad-KDRP-CDglyTK) and the cytomegalovirus (CMV) promoter (Ad-CMV
      CDglyTK) were established and transfected into the KDR-expressing MCF7 human
      breast cancer, EC304 human vascular endothelial and LS174T human colon carcinoma,
      which does not express KDR, cell lines. The selective killing efficiency and
      specificity of the double suicide gene system were measured in vitro by the
      analysis of cellular proliferation and assayed in vivo by subcutaneous injection
      of MCF7 cells into nude mice. The microvessel density (MVD) in the transplanted
      tumor was determined by immunohistochemical staining of CD34 cells. Our results
      showed that the transgenic CDglyTK genes were expressed in three cell lines
      (MCF7, ECV304 and LS174T) infected with Ad-CMV-CDglyTK. However, of the cells
      infected with Ad-KDRP-CDglyTK, the transgenic CDglyTK gene was only expressed in
      the KDR-expressing MCF7 and ECV304 cells, but not in the KDR-deficient LS174T
      cells. Cell proliferation was significantly reduced in a dose-dependent manner by
      pre-treatment with ganciclovir (GCV) and 5-fluorocytosine (5-FC) in MCF7 and
      ECV304 cells with transfected KDRP-CDglyTK genes and the three cell lines
      transfected with the CMV-CDglyTK genes. Similar results were not observed in the
      LS174T cells with transfected KDRP-CDglyTK genes. The results of this study show
      that the tumor-targeted expression of CDglyTK driven by the KDR promoter has a
      high specificity and performance. The killing effect of the CD/TK fusion gene in
      the target cells was significantly increased compared with the single suicide
      gene. The cell cycle of MCF7 and ECV304 cells transfected with KDRP-CDglyTK genes
      was arrested at the S phase following treatment with the prodrugs. The tumors
      formed by the MCF7 cells with the double suicide gene system were much smaller
      and the MVD of the tumor tissue was significantly decreased compared with the
      control. This study demonstrates that tumor-targeted expression of the CDglyTK
      gene driven by the KDR promotor may be a novel strategy for the gene therapy of
      human breast cancer.

PMID- 22641385
TI  - Alterations of the base excision repair gene MUTYH in sporadic colorectal cancer.
AB  - The base excision repair gene MUTYH encodes glycosylase which removes adenine
      residues mispaired with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHG). Biallelic
      germline mutations of the MUTYH gene are known to cause multiple colorectal
      adenomas including polyposis and cancer, mostly due to G:C?T:A transversions in
      proto-oncogenes or tumor suppressor genes. The risk of colorectal cancer (CRC) in
      monoallelic mutation carriers of MUTYH is estimated to be higher in comparison
      with non-carriers. To investigate the possible role in sporadic CRC, we examined
      alterations of the MUTYH gene including somatic mutations and allelic loss in 101
      cases of sporadic CRC, together with the KRAS mutation in some cases. MUTYH
      mutations in cancer DNA were detected in 3 cases, while mutations were also found
      in DNA samples from normal tissues, indicating that all were germline mutations.
      Allelic loss at the MUTYH locus was found in 10 of 51 (20.0%) CRC cases and KRAS
      mutations were found in 33 of the 101 (32.7%) samples. There was no significant
      difference in the rate of G:C?T:A transversion in KRAS between cases with allelic
      loss (1 of 10, 10.0%) and without allelic loss (9 of 41, 22.0%). Investigation of
      quantitative allelic imbalance at SNP rs3219489 of MUTYH showed that CRC cases
      with C allele dominance (minor type corresponding to His) were more frequently
      detected with G:C?T:A transversions than in those with G allele dominance (major
      type corresponding to Gln). In conclusion, somatic alterations of MUTYH in
      sporadic CRC were rare, similar to other DNA repair genes. However, it is
      possible that unknown mutations of regions not analyzed in this study and
      epigenetic changes of the promoter region of MUTYH may contribute to the disease.

PMID- 22641386
TI  - Comment on the paper "Extensive theoretical studies of a new energetic material:
      tetrazino-tetrazine-tetraoxide (TTTO)" by Xinli Song, Jicun Li, Hua Hou, and
      Baoshan Wang.
AB  - Discrepancies are noted in the implementation and presentation of the ccCA
      methodology in a previous publication, "Extensive Theoretical Studies of a New
      Energetic Material: Tetrazino-tetrazine-tetraoxide (TTTO)" by Xinli Song, Jicun
      Li, Hua Hou, and Baoshan Wang. The enthalpy of formation for TTTO has been re
      evaluated using the correct implementation of the ccCA methodology, demonstrating
      the results to be comparable to those of other ab initio composite methods.

PMID- 22641387
TI  - Chlorinated and brominated dibenzo-p-dioxins and dibenzofurans in surface
      sediment from Taihu Lake, China.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polybrominated
      dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) in surface sediment samples from
      Taihu Lake--an important water supply of the Yangtze River Delta, China--were
      investigated in the present study. Concentrations of PCDD/Fs ranged from 0.91 to
      4.8 pg TEQ g(-1) dw (mean: 2.9 pg TEQ g(-1) dw, TEQ: Toxic Equivalent), which
      were all higher than the threshold effect level established by interim sediment
      quality guidelines in Canada (0.85 pg TEQ g(-1) dw). The levels of PBDD/Fs ranged
      from 0.16 to 1.6 pg TEQ g(-1) dw (mean: 0.52 pg TEQ g(-1) dw) and accounted for 5
      33% (mean: 14%) of the total PCDD/Fs and PBDD/Fs TEQ. Comparatively, the
      abundance of sedimentary PCDD/Fs in the three regions (Meiliang Bay, Gonghu Bay,
      and Xukou Bay) showed a decreasing trend from the inflow region to the outflow
      region, while no significant difference was observed among their 2,3,7,8-PBDD/Fs
      levels, which suggested that the sources of PCDD/Fs and PBDD/Fs differed in this
      area. Principal component analysis suggested that the historical production/usage
      of pentachlorophenol and sodium pentachlorophenate was the dominant source of
      PCDD/Fs in the sediment of these regions. Although the specific sources of
      PBDD/Fs in the sediment of Taihu Lake were unclear, it was suspected to be due to
      atmospheric deposition; however, an additional study is needed to confirm this.

PMID- 22641388
TI  - Electromechanical and elastic probing of bacteria in a cell culture medium.
AB  - Rapid phenotype characterization and identification of cultured cells, which is
      needed for progress in tissue engineering and drug testing, requires an
      experimental technique that measures physical properties of cells with sub-micron
      resolution. Recently, band excitation piezoresponse force microscopy (BEPFM) has
      been proven useful for recognition and imaging of bacteria of different types in
      pure water. Here, the BEPFM method is performed for the first time on
      physiologically relevant electrolyte media, such as Dulbecco's phosphate-buffered
      saline (DPBS) and Dulbecco's modified Eagle's medium (DMEM). Distinct
      electromechanical responses for Micrococcus lysodeikticus (Gram-positive) and
      Pseudomonas fluorescens (Gram-negative) bacteria in DPBS are demonstrated. The
      results suggest that mechanical properties of the outer surface coating each
      bacterium, as well as the electrical double layer around them, are responsible
      for the BEPFM image formation mechanism in electrolyte media.

PMID- 22641389
TI  - Dorsorostral snout muscles in the rat subserve coordinated movement for whisking
      and sniffing.
AB  - Histochemical examination of the dorsorostral quadrant of the rat snout revealed
      superficial and deep muscles that are involved in whisking, sniffing, and airflow
      control. The part of M. nasolabialis profundus that acts as an intrinsic
      (follicular) muscle to facilitate protraction and translation of the vibrissae is
      described. An intraturbinate and selected rostral-most nasal muscles that can
      influence major routs of inspiratory airflow and rhinarial touch through their
      control of nostril configuration, atrioturbinate and rhinarium position, were
      revealed.

PMID- 22641390
TI  - Effect of levosimendan in patients with severe systolic heart failure and
      worsening renal function.
AB  - BACKGROUND: Levosimendan, a calcium sensitizer, increases the sensitivity of the
      heart to calcium, thus increasing myocardial contractility without a rise in
      intracellular calcium. It was recently shown that levosimendan is beneficial in
      improving renal function. However, it remains to be established that the
      beneficial effect is differentially related to renal status during index event.
      OBJECTIVE: The purpose of the current study was to determine whether levosimendan
      could improve renal outcome in acute decompensated heart failure patients with
      and without worsening renal function. METHODS: Forty-five consecutive patients
      who had a reduced glomerular filtration rate and had at least two consecutive
      data regarding renal function prior to administration of levosimendan were
      enrolled in the study. Patients were classified into two groups as those with and
      without worsening renal function based on an increase in serum creatinine >0.3
      mg/dL. RESULTS: A significant improvement was noted in renal function in patients
      with worsening renal function (serum creatinine from 1.4 +/- 0.16 to 1.21 +/-
      0.23 mg/dL, p=0.001 and glomerular filtration rate level from 48.9 +/- 15 to 59.3
      +/- 21.8 mL/min/m2, p=0.011), while there was no significant improvement in those
      without worsening renal function (serum creatinine from 1.29 +/- 0.33 to 1.37 +/-
      0.66 mg/dL, p=0.240 and glomerular filtration rate level from 53.7 +/- 17.6 to
      52.9 +/- 21.4 mL/min/m2, p=0.850). CONCLUSION: Levosimendan appears to provide a
      renal-enhancing effect in patients with severe, acute decompensated systolic
      heart failure and worsening renal function. Consideration of this differential
      effect might help obtain beneficial renal outcomes.

PMID- 22641391
TI  - Inferior Vena Cava collapsibility and heart failure signs and symptoms: new
      insights about possible links.
AB  - BACKGROUND: In chronic heart failure patients (CHF), ultrasound measurement of
      inferior vena cava collapsibility index (IVCCI) has been proposed to yield
      careful assessment and grading of the hemodynamic congestion. OBJECTIVE: The
      purpose of this study was to correlate the findings of physical examination with
      IVCCI in CHF patients. METHODS: According to a retrospective cohort design, we
      analyzed 54 CHF patients with right or biventricular CHF, belonging to III NYHA
      class. We planned to determine whether any basal IVCCI range would be able to
      predict persistent or worsening clinical congestion found at the end of
      subsequent follow up (i.e. after 1-2 months of oral optimized therapy). For this
      purpose, the patients were subdivided by three groups according to the basal
      IVCCI value: <= 15% (13 pts), 16 - 40% (21 pts) and > 40% (20 pts).Several
      clinical criteria of congestion were compared across the three groups and
      subsequently entered in the Cox multivariate model. RESULTS: Multivariate
      predictors of high congestion score were jugular venous distension (HR: 13,38 95%
      C.I.: 2,13 - 84 p = 0,0059) and rales (HR: 11 95% C.I : 1,45 - 83,8 p = 0,0213).
      IVCCI <= 15% was always associated with high congestion score at the second
      visit; but IVCCI <= 15% failed to predict high congestion score at the second
      visit. CONCLUSION: In CHF setting, low IVCCI did not reliably predict high
      congestion score. Nevertheless, the cluster with IVCCI <= 15% was always found
      associated with signs and symptoms from both right and left-sided decompensated
      CHF.

PMID- 22641392
TI  - Prognostic value of B-type natriuretic peptide in the mortality of patients with
      acute coronary syndrome.
AB  - BACKGROUND: The prognostic value of BNP in acute coronary syndrome (ACS) has been
      repeatedly assessed, but not completely well established. Literature data for
      establishing the best time for assessing BNP, be it on hospital admission or
      after coronary intervention, are controversial. OBJECTIVE: To analyze BNP in non
      ST segment elevation ACS (NSTE-ACS) in the long term, and to assess the
      association between BNP (pg/ml), death, coronary anatomy, and TIMI Risk Score.
      METHODS: Forty patients with NSTE-ACS and troponin>0.50 ng/ml had their BNP
      levels measured on admission and 96 hours after, and were followed up for four
      years. The difference between the two measures was assessed by use of Wilcoxon
      test (p<0.05). The ROC curve was used to evaluate 96-hour BNP accuracy as a death
      predictor, and logistic regression was used to assess a possible confounding
      factor among 96-hour BNP, age, and outcome. RESULTS: There was an increase in the
      96-hour BNP (148 on admission vs. 267 after 96 hours; p=0.04). Thirteen patients
      died. For the 300 pg/ml cutoff, 96-hour BNP was a death predictor (sensitivity,
      92.30%; specificity, 77.80%; positive predictive value, 66.70%; negative
      predictive value, 95.50%). The area under the ROC curve was 0.92. A 7.4-time
      increase in the relative risk of death in four years was observed with a 96-hour
      BNP> 300 pg/ml (95% CI 1.90 a 29.30 p<0.01). An association between 96-hour BNP
      and TIMI Risk Score was observed (p<0.01). An association was observed between
      the increase in 96-hour BNP and multivessel disease (p=0.02). CONCLUSION: In NSTE
      ACS with positive troponin, 96-hour BNP can be a tool for risk stratification.

PMID- 22641393
TI  - Prevalence of resistant hypertension in non-elderly adults: prospective study in
      a clinical setting.
AB  - BACKGROUND: In face of variable definitions and sampling criteria, the real
      prevalence of resistant hypertension in a clinical setting is unknown. OBJECTIVE:
      We investigated the prevalence of true resistant hypertension in an outpatient
      hypertension clinic. METHODS: True resistant hypertension was diagnosed when
      white coat phenomenon, lack of compliance and secondary hypertension were
      excluded in patients with blood pressure >= 140/90 mmHg in two consecutive
      visits, despite to be using three blood pressure-lowering agents, including a
      diuretic. RESULTS: In the total, 606 patients, with 35 to 65 years of age, mostly
      women, with BP of 156.8 +/- 23.8 mmHg by 91.9 +/- 15.6 mmHg and a BMI of 29.7 +/-
      5.9 Kg/m2 were sequentially evaluated. One hundred and six patients using three
      BP drugs had uncontrolled blood pressure (17.5% of the whole sample) in the first
      visit. Eighty-six patients (81% of the patients with uncontrolled BP in the first
      evaluation) returned for the confirmatory evaluation. Twenty-five had controlled
      BP, 21 had evidence of low adherence to treatment, 13 had white coat phenomenon
      and 9 had secondary hypertension, leaving only 18 patients (20.9% of those
      uncontrolled in the confirmatory visit and 3% of the whole sample) with true
      resistant hypertension. Considering patients with secondary hypertension as cases
      of resistant hypertension, the prevalence of resistant hypertension increased to
      4.5%. CONCLUSION: The frequency of patients with true resistant hypertension in
      non-elderly patients is low in a clinical setting, and is not substantially
      increased with the inclusion of patients with secondary hypertension.

PMID- 22641394
TI  - Leptin and aldosterone in sympathetic activity in resistant hypertension with or
      without type 2 diabetes.
AB  - BACKGROUND: The finding of adipocyte-derived hormone leptin as an overstimulator
      of sympathetic activity brought a new perspective to the pathophysiological
      mechanisms of obesity-hypertension. OBJECTIVES: As aldosterone also increases
      sympathetic activity, we aimed to assess the relationship between sympathetic
      overactivity and plasma leptin and aldosterone levels in resistant hypertension
      (RHTN), comparing the groups with and without T2D. METHODS: Twenty-five RHTN
      patients underwent ambulatory electrocardiography to analyze heart rate
      variability (HRV) in time and frequency domains, which were stratified into two
      periods: 24 hours and daytime (DT), comprising the records between 2:00 p.m to
      6:00 p.m (time domain) and one hour at 3:00 p.m (frequency domain). RESULTS: T2D
      group (n=10) had higher serum aldosterone and plasma leptin levels than the non
      T2D (n=15) (26.0 +/- 11.5 vs. 16.9 +/- 7.0 ng/dL - p=0.021; 81.368.7 +/- 47.086.1
      vs 41.228.1 +/- 24.523.1 pg/mL - p=0.048, respectively). Both groups had
      aldosterone correlated with HRV in frequency domain. Non-T2D had aldosterone
      correlated with DT low frequency in normalized units (LF nu) (r=0.6 [0.12-0.85]
      p=0.018) and DT high frequency in normalized units (HF nu) (r=-0.6 [-0.85- -0.12]
      p=0.018). Type-2-diabetes group had aldosterone correlated with DT LF nu (r=0.72
      [0.16-0.93] p=0.019) and DT HF nu (r=-0.72 [-0.93- -0.16] p=0.019). However,
      despite of the importance of leptin in sympathetic overactivity in hypertension,
      leptin did not correlate with HRV. CONCLUSION: Aldosterone seems to overdrive
      sympathetic activity in RHTN with and without T2D. This information combined with
      the clinical efficacy of mineralocorticoid receptor blocker in RHTN may reinforce
      that aldosterone is a major player to be a therapeutic target in RHTN.

PMID- 22641395
TI  - Patterning techniques for metal organic frameworks.
AB  - The tuneable pore size and architecture, chemical properties and
      functionalization make metal organic frameworks (MOFs) attractive versatile
      stimuli-responsive materials. In this context, MOFs hold promise for industrial
      applications and a fervent research field is currently investigating MOF
      properties for device fabrication. Although the material properties have a
      crucial role, the ability to precisely locate the functional material is
      fundamental for device fabrication. In this progress report, advancements in the
      control of MOF positioning and precise localization of functional materials
      within MOF crystals are presented. Advantages and limitations of each reviewed
      technique are critically investigated, and several important gaps in the
      technological development for device fabrication are highlighted. Finally,
      promising patterning techniques are presented which are inspired by previous
      studies in organic and inorganic crystal patterning for the future of MOF
      lithography.

PMID- 22641396
TI  - Does occupational lifting and carrying among female health care workers
      contribute to an escalation of pain-day frequency?
AB  - BACKGROUND: The aim of the study was to investigate if different frequencies,
      loads and trunk postures of occupational lifting and carrying increases the risk
      of sub-chronic (1-30 days last 12 months) low back pain (LBP) to become
      persistent (>30 days last 12 months) among female health care workers. METHODS:
      Female health care workers answered a questionnaire about occupational lifting or
      carrying frequency (rarely, occasionally and frequently), load (low: 1-7 kg,
      moderate: 8-30 kg and heavy: >30 kg) and trunk posture (upright or forward bent
      back), and days with LBP in 2005 and 2006. RESULTS: The odds ratio (OR) for
      developing persistent LBP in 2006 from these characteristics of occupational
      lifting and carrying was investigated with multi-adjusted logistic regressions
      among female health care workers with sub-chronic LBP (n = 2381) in 2005. Among
      health care workers with sub-chronic LBP, increased risk of persistent LBP was
      found from frequently lifting or carrying with forward bent back of moderate
      loads (OR: 1.63; 95% CI: 1.15-2.33) and heavy loads (OR: 1.56; 95% CI: 1.04
      2.34). No increased risk for LBP to develop into a persistent condition was found
      for frequent lifting with upright back, frequent lifting or carrying of light
      loads, or occasionally lifting or carrying of any loads. CONCLUSIONS: Preventive
      initiatives for sub-chronic LBP to develop into a persistent condition ought to
      focus on reducing frequent lifting and carrying of moderate and heavy loads with
      forward bent back.

PMID- 22641397
TI  - Catalyst-free fabrication of graphene nanosheets without substrates using
      multiwalled carbon nanotubes and a spark plasma sintering process.
AB  - Catalyst-free graphene nanosheets without substrates were synthesized using pure
      solid carbon sources of multiwalled carbon nanotubes (MWCNTs) and a spark plasma
      sintering (SPS) process. Single and few-hundred-nanometer graphene nanosheets
      were formed from gas-phase carbon atoms which were directly evaporated from
      MWCNTs at a local high temperature.

PMID- 22641399
TI  - Atypical thrombotic thrombocytopenic purpura in a middle-aged woman who presented
      with a recurrent stroke.
AB  - An atypical clinical presentation makes TTP diagnosis difficult, which prevents
      prompt management of TTP. This case highlights the importance of early
      recognition of TTP in patients with atypical presentations who may not have the
      expected clinical or laboratory findings. The level of suspicion should be
      especially high in young and middle-aged patients with strokes or acute coronary
      syndrome who do not have other risk factors for cardiovascular events. This is
      particularly so for those patients who have a previous episode of TTP or patients
      with subtle laboratory abnormalities, which may suggest the potential existence
      of a thrombotic microangiopathic process.

PMID- 22641400
TI  - Insight into the effects of graphene oxide sheets on the conformation and
      activity of glucose oxidase: towards developing a nanomaterial-based protein
      conformation assay.
AB  - Protein conformation associates with particular properties of proteins and
      relates to protein-mediated diseases. Detailed elucidation of secondary and
      tertiary formation, stability, and the structural and dynamic properties of
      proteins has been one of the main topics studied in chemistry and biology. In
      this work, the conformation changes in glucose oxidase (GOx) induced by the
      graphene oxide (GO) sheets were studied in detail by various spectroscopic
      techniques including ultraviolet-visible (UV-vis) absorption, fluorescence, and
      circular dichroism (CD) spectroscopy. The results indicated that GOx underwent
      substantial conformation changes after assembling on the surface of GO. The
      interaction of GOx with GO could induce the exposure of the FAD (flavin adenine
      dinucleotide) moiety to solvent and transfer tryptophan (Trp) residues to a more
      hydrophobic environment. The calculation from CD spectra showed that GO could
      induce the conversion of alpha-helix to beta-sheet structures, even unfolding of
      the protein. These alterations in the conformation of GOx resulted in a
      significant decrease in the catalytic activity of the enzyme in glucose
      oxidation. The possible reasons for these conformation changes in GOx are also
      discussed. This work not only provides insight into the interaction between
      atomically flat graphitic structures and various biological systems but also
      creates a framework for analyzing the biosafety of nanomaterials in terms of the
      biological behavior of biomacromolecules. The results obtained here can direct
      the further applications of the nanomaterials.

PMID- 22641398
TI  - Genetic modifiers of sickle cell disease.
AB  - Sickle cell anemia is associated with unusual clinical heterogeneity for a
      Mendelian disorder. Fetal hemoglobin concentration and coincident alpha
      thalassemia, both which directly affect the sickle erythrocyte, are the major
      modulators of the phenotype of disease. Understanding the genetics underlying the
      heritable subphenotypes of sickle cell anemia would be prognostically useful,
      could inform personalized therapeutics, and might help the discovery of new
      "druggable" pathophysiologic targets. Genotype-phenotype association studies have
      been used to identify novel genetic modifiers. In the future, whole genome
      sequencing with its promise of discovering hitherto unsuspected variants could
      add to our understanding of the genetic modifiers of this disease.

PMID- 22641401
TI  - Cysticercosis and echinococcosis.
AB  - Cysticercosis and cystic echinococcosis are zoonotic parasitic diseases commonly
      transmitted by livestock animals. Past and future efforts to reduce transmission
      of these diseases adopt a One Health approach where control measures are
      implemented largely in the parasites' animal hosts in order to bring about,
      indirectly, a reduction in human disease. New and highly effective vaccines have
      been produced which are capable of preventing infections with Echinococcus
      granulosus (cystic echinococcosis) and Taenia solium (cysticercosis) in their
      animal intermediate hosts. Application of vaccines, together with taeniacides in
      the parasites' definitive hosts, provides new opportunities for control of these
      diseases and a reduction in the global burden of human cysticercosis and cystic
      echinococcosis. 

PMID- 22641402
TI  - Association between the C3435T single-nucleotide polymorphism of multidrug
      resistance 1 gene and risk of gastric cancer.
AB  - The multidrug resistance 1 (MDR1) gene encodes P-glycoprotein, which confers
      resistance to antineoplastic drugs, but also affects the kinetic disposition of
      certain drugs and carcinogens. The C3435T polymorphism of the MDR1 gene may
      influence the transport and excretion of carcinogens, increasing the risk of
      cancer. The aim of this study was to evaluate the association between this
      polymorphism and the risk of gastric cancer (GC). Ninety-eight patients with non
      cardia GC and 203 healthy subjects participated in the study. DNA was extracted
      from leukocytes and the MDR1 polymorphism was analyzed using PCR-RFLP. Serology
      was performed by ELISA for the investigation of infection with Helicobacter
      pylori. No significant difference in the genotype (p=0.668) or allele (p=0.745)
      frequency of the C3435T polymorphism was observed between the GC and control
      groups. There was no association between the genotypes studied and the risk of GC
      in patients infected with H. pylori (p=0.662). Patient survival was not
      correlated with the genotypes studied (p=0.454). No correlation was observed
      between the C3435T polymorphism of the MDR1 gene and GC risk or prognosis in the
      population studied.

PMID- 22641404
TI  - Report on the African teaching tools workshops.

PMID- 22641403
TI  - Occupational solvent exposure and cognition: does the association vary by level
      of education?
AB  - OBJECTIVE: Chronic occupational solvent exposure is associated with long-term
      cognitive deficits. Cognitive reserve may protect solvent-exposed workers from
      cognitive impairment. We tested whether the association between chronic solvent
      exposure and cognition varied by educational attainment, a proxy for cognitive
      reserve. METHODS: Data were drawn from a prospective cohort of French national
      gas and electricity (GAZEL) employees (n = 4,134). Lifetime exposure to 4 solvent
      types (chlorinated solvents, petroleum solvents, benzene, and nonbenzene aromatic
      solvents) was assessed using a validated job-exposure matrix. Education was
      dichotomized at less than secondary school or below. Cognitive impairment was
      defined as scoring below the 25th percentile on the Digit Symbol Substitution
      Test at mean age 59 (SD 2.8; 88% of participants were retired at testing). Log
      binomial regression was used to model risk ratios (RRs) for poor cognition as
      predicted by solvent exposure, stratified by education and adjusted for
      sociodemographic and behavioral factors. RESULTS: Solvent exposure rates were
      higher among less-educated patients. Within this group, there was a dose-response
      relationship between lifetime exposure to each solvent type and RR for poor
      cognition (e.g., for high exposure to benzene, RR = 1.24, 95% confidence interval
      1.09-1.41), with significant linear trends (p < 0.05) in 3 out of 4 solvent
      types. Recency of solvent exposure also predicted worse cognition among less
      educated patients. Among those with secondary education or higher, there was no
      significant or near-significant relationship between any quantification of
      solvent exposure and cognition. CONCLUSIONS: Solvent exposure is associated with
      poor cognition only among less-educated individuals. Higher cognitive reserve in
      the more-educated group may explain this finding.

PMID- 22641405
TI  - Noninvasive microscopic imaging of sensory receptors in neuropathy.

PMID- 22641406
TI  - Journal club: Intrathecal effects of daclizumab treatment of multiple sclerosis.

PMID- 22641407
TI  - Pearls & oy-sters: Hashimoto encephalopathy.

PMID- 22641408
TI  - Teaching neuroimages: MRI time lag with acute disseminated encephalomyelitis.

PMID- 22641409
TI  - Effects of repeated mild head impacts in contact sports: adding it up.

PMID- 22641410
TI  - Size and shape of nanoclusters: single-shot imaging approach.
AB  - A method of single-shot imaging via aberration-corrected scanning transmission
      electron microscopy equipped with high angle annular dark-field detector (STEM
      HAADF) has been applied to size-selected gold model catalysts (Au(25)  and Au(39)
      ) on hydroxyapatite. Through quantitative intensity analysis, the size, in terms
      of number of atoms as well as 3D shape of the clusters are obtained.

PMID- 22641411
TI  - Transparent, optical, pressure-sensitive artificial skin for large-area
      stretchable electronics.
AB  - Optical pressure sensors are highly responsive and are unaffected by surrounding
      parameters such as electronic noise, humidity, temperature, etc. A new type of
      optical pressure sensor is described that demonstrates the stretchability and
      transparency of a polydimethylsiloxane waveguide, while also serving as a
      substrate. The pressure sensors are both robust and easy to fabricate over a
      large area.

PMID- 22641412
TI  - Behcet's disease with active uveitis: detection of serum protein biomarkers using
      MALDI-TOF-MS.
AB  - Behcet's Disease (BD) is a multisystem autoimmune disorder that lacks sensitive
      and specific diagnostic methods. The aim of this study was to identify potential
      biomarkers specific for BD and to establish a diagnostic model. Serum samples
      from patients with BD, Vogt-Koyanagi-Harada syndrome (VKH), and healthy controls
      (HC) were randomly divided into a training set (49 BD, 31 VKH, and 48 HC) and a
      testing set (13 BD, 10 VKH, and 11 HC). Proteomic mass spectra were generated by
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS). Thirty-nine differential m/z peaks associated with BD were
      identified, and the m/z peaks at 1,644, 1,711, 2,023, 4,347, 6,628, and 8,559
      were used to construct a model for the diagnosis of BD. This diagnostic model can
      distinguish BD from non-BD controls with a sensitivity of 83.67% (41/49) and a
      specificity of 89.87% (71/79). BD was detected in our blinded testing set with
      good sensitivity and specificity of 84.6 and 90.48%, respectively. The results
      suggested that proteomic fingerprint technology combining magnetic beads with
      MALDI-TOF-MS has potential for the diagnosis of BD. The biomarker classification
      model was suitable for preliminary identification of BD and could potentially
      serve as a useful tool for BD diagnosis and differential diagnosis.

PMID- 22641413
TI  - A simple test of muscle coactivation estimation using electromyography.
AB  - In numerous motor tasks, muscles around a joint act coactively to generate
      opposite torques. A variety of indexes based on electromyography signals have
      been presented in the literature to quantify muscle coactivation. However, it is
      not known how to estimate it reliably using such indexes. The goal of this study
      was to test the reliability of the estimation of muscle coactivation using
      electromyography. Isometric coactivation was obtained at various muscle
      activation levels. For this task, any coactivation measurement/index should
      present the maximal score (100% of coactivation). Two coactivation indexes were
      applied. In the first, the antagonistic muscle activity (the lower
      electromyographic signal between two muscles that generate opposite joint
      torques) is divided by the mean between the agonistic and antagonistic muscle
      activations. In the second, the ratio between antagonistic and agonistic muscle
      activation is calculated. Moreover, we computed these indexes considering
      different electromyographic amplitude normalization procedures. It was found that
      the first algorithm, with all signals normalized by their respective maximal
      voluntary coactivation, generates the index closest to the true value (100%),
      reaching 92 +/- 6%. In contrast, the coactivation index value was 82 +/- 12% when
      the second algorithm was applied and the electromyographic signal was not
      normalized (P < 0.04). The new finding of the present study is that muscle
      coactivation is more reliably estimated if the EMG signals are normalized by
      their respective maximal voluntary contraction obtained during maximal
      coactivation prior to dividing the antagonistic muscle activity by the mean
      between the agonistic and antagonistic muscle activations.

PMID- 22641414
TI  - Furosemide is associated with acute kidney injury in critically ill patients.
AB  - Acute kidney injury (AKI) is common in critically ill patients. Diuretics are
      used without any evidence demonstrating a beneficial effect on renal function.
      The objective of the present study is to determine the incidence of AKI in an
      intensive care unit (ICU) and if there is an association between the use of
      furosemide and the development of AKI. The study involved a hospital cohort in
      which 344 patients were consecutively enrolled from January 2010 to January 2011.
      A total of 132 patients (75 females and 57 males, average age 64 years) remained
      for analysis. Most exclusions were related to ICU discharge in the first 24 h.
      Laboratory, sociodemographic and clinical data were collected until the
      development of AKI, medical discharge or patient death. The incidence of AKI was
      55% (95%CI = 46-64). The predictors of AKI found by univariate analysis were
      septic shock: OR = 3.12, 95%CI = 1.36-7.14; use of furosemide: OR = 3.27, 95%CI =
      1.57-6.80, and age: OR = 1.02 (95%CI = 1.00-1.04). Analysis of the subgroup of
      patients with septic shock showed that the odds ratio of furosemide was 5.5
      (95%CI = 1.16-26.02) for development of AKI. Age, use of furosemide, and septic
      shock were predictors of AKI in critically ill patients. Use of furosemide in the
      subgroup of patients with sepsis/septic shock increased (68.4%) the chance of
      development of AKI when compared to the sample as a whole (43.9%).

PMID- 22641416
TI  - Arginine induces GH gene expression by activating NOS/NO signaling in rat
      isolated hemi-pituitaries.
AB  - The amino acid arginine (Arg) is a recognized secretagogue of growth hormone
      (GH), and has been shown to induce GH gene expression. Arg is the natural
      precursor of nitric oxide (NO), which is known to mediate many of the effects of
      Arg, such as GH secretion. Arg was also shown to increase calcium influx in
      pituitary cells, which might contribute to its effects on GH secretion. Although
      the mechanisms involved in the effects of Arg on GH secretion are well
      established, little is known about them regarding the control of GH gene
      expression. We investigated whether the NO pathway and/or calcium are involved in
      the effects of Arg on GH gene expression in rat isolated pituitaries. To this
      end, pituitaries from approximately 170 male Wistar rats (~250 g) were removed,
      divided into two halves, pooled (three hemi-pituitaries) and incubated or not
      with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO
      donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine
      monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60
      min later. The NO acceptor hemoglobin (0.3 uM) blunted the effect of SNP, and the
      combined treatment with Arg and L-NAME (a NO synthase (NOS) inhibitor, 55 mM)
      abolished the stimulatory effect of Arg on GH gene expression. The calcium
      channel inhibitor nifedipine (3 uM) also abolished Arg-induced GH gene
      expression. The present study shows that Arg directly induces GH gene expression
      in hemi-pituitaries isolated from rats, excluding interference from
      somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover,
      the data demonstrate that the NOS/NO signaling pathway and calcium mediate the
      Arg effects on GH gene expression.

PMID- 22641417
TI  - Prolonged acceptance of skin grafts induced by B cells places regulatory T cells
      on the histopathology scene.
AB  - The participation of regulatory T (Treg) cells in B cell-induced T cell tolerance
      has been claimed in different models. In skin grafts, naive B cells were shown to
      induce graft tolerance. However, neither the contribution of Treg cells to B cell
      induced skin tolerance nor their contribution to the histopathological diagnosis
      of graft acceptance has been addressed. Here, using male C57BL/6 naive B cells to
      tolerize female animals, we show that skin graft tolerance is dependent on CD25+
      Treg cell activity and independent of B cell-derived IL-10. In fact, B cells from
      IL-10-deficient mice were able to induce skin graft tolerance while Treg
      depletion of the host inhibited 100% graft survival. We questioned how Treg cell
      mediated tolerance would impact on histopathology. B cell-tolerized skin grafts
      showed pathological scores as high as a rejected skin from naive, non-tolerized
      mice due to loss of skin appendages, reduced keratinization and mononuclear cell
      infiltrate. However, in tolerized mice, 40% of graft infiltrating CD4+ cells were
      FoxP3+ Treg cells with a high Treg:Teff (effector T cell) ratio (6:1) as compared
      to non-tolerized mice where Tregs comprise less than 8% of total infiltrating CD4
      cells with a Treg:Teff ratio below 1:1. These results render Treg cells an
      obligatory target for histopathological studies on tissue rejection that may help
      to diagnose and predict the outcome of a transplanted organ.

PMID- 22641419
TI  - Nitro group as a new anchoring group for organic dyes in dye-sensitized solar
      cells.
AB  - An organic dye JY1 bearing a nitro group was designed, synthesized and applied in
      DSCs. An unusual colour change was observed when the voltage applied to the
      device was reversed which was accompanied by a five-fold increase in the cell
      efficiency. We propose that applying a bias enabled the attachment of nitro
      groups to the TiO(2) surface.

PMID- 22641418
TI  - Behavioral meaningful opioidergic stimulation activates kappa receptor gene
      expression.
AB  - The periaqueductal gray (PAG) has been reported to be a location for opioid
      regulation of pain and a potential site for behavioral selection in females.
      Opioid-mediated behavioral and physiological responses differ according to the
      activity of opioid receptor subtypes. The present study investigated the effects
      of the peripheral injection of the kappa-opioid receptor agonist U69593 into the
      dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene
      activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the
      beginning of the study were randomly divided into 2 groups for maternal behavior
      and gene expression experiments. On day 5, pups were removed at 7:00 am and
      placed in another home cage that was distant from their mother. Thirty minutes
      after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or
      0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal
      behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and
      full maternal behavior were scored. The results showed that U69593 administration
      inhibited maternal behavior (P < 0.05) because a lower percentage of kappa group
      dams showed retrieval of first pup, retrieving all pups, grouping, crouching and
      displaying full maternal behavior compared to the saline group. Opioid gene
      expression was evaluated using real-time reverse-transcription polymerase chain
      reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in
      both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant
      effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid
      receptors in the PAG may be modulated by single opioid receptor stimulation and
      behavioral meaningful opioidergic transmission in the adult female might occur
      simultaneously to specific changes in gene expression of kappa-opioid receptor
      subtype. This is yet another alert for the complex role of the opioid system in
      female reproduction.

PMID- 22641420
TI  - Lenalidomide in multiple myeloma: Current status and future potential.
AB  - The clinical development of lenalidomide (RevlimidTM), then pomalidomide
      (ActimidTM) as members of immunomodulatory drugs (IMiDs) for the treatment of
      multiple myeloma (MM), exemplifies how insight into disease biology can lead to
      design of effective therapeutic agents. Increased experience and understanding of
      IMiD's diverse biological effects has lead to rational design of lenalidomide
      based treatment-regimens over recent years. However, much about lenalidomide is
      yet to be understood and fully exploited. Here, we review what is known of
      lenalidomide's biological effects, clinical certainties and uncertainties in the
      treatment of MM, and explore its future potential with other synergistic
      therapeutic agents.

PMID- 22641421
TI  - Controlled AFM detachments and movement of nanoparticles: gold clusters on HOPG
      at different temperatures.
AB  - The effect of temperature on the onset of movement of gold nanoclusters (diameter
      27 nm) deposited on highly oriented pyrolytic graphite (HOPG) has been studied by
      atomic force microscopy (AFM) techniques. Using the AFM with amplitude modulation
      (tapping mode AFM) we have stimulated and controlled the movement of individual
      clusters. We show how, at room temperature, controlled detachments and smooth
      movements can be obtained for clusters having dimensions comparable to or smaller
      than the tip radius. Displacement is practically visible in real time and it can
      be started and stopped easily by adjusting only one parameter, the tip amplitude
      oscillation. Analysing the energy dissipation signal at the onset of nanocluster
      sliding we evaluated a detachment threshold energy as a function of temperature
      in the range 300-413 K. We also analysed single cluster thermal induced
      displacement and combining this delicate procedure with AFM forced movement
      behaviour we conclude that detachment threshold energy is directly related to the
      activation energy of nanocluster diffusion and it scales linearly with
      temperature as expected for a single-particle thermally activated process.

PMID- 22641424
TI  - BAFF/BLyS inhibitors: A new prospect for treatment of systemic lupus
      erythematosus.
AB  - In November 2009, Human Genome Sciences and Glaxo-Smith Kline [HGS (Rockville,
      Maryland) and GSK, respectively] announced that Belimumab, a neutralizing
      antibody to the tumour necrosis factor (TNF)-like ligand, B-cell activating
      factor (BAFF belonging to the TNF family, also named BLyS), met the primary
      endpoints in two phase III clinical trials in systemic lupus erythematosus (SLE,
      lupus). In March 2011, Belimumab was approved by the US Federal Drug Agency for
      treatment of SLE patients; this was followed in May with approval by the European
      Medicines Agency for use in the European Union. This is an exciting development
      as it is the first successful late-stage clinical trial in SLE in over 40 years.
      In the light of this breakthrough, we review the key data and research outcomes
      and examine how blocking BAFF in patients with SLE significantly improves
      clinical outcomes.

PMID- 22641422
TI  - Haemoglobin modulates salicylate and jasmonate/ethylene-mediated resistance
      mechanisms against pathogens.
AB  - Nitric oxide (NO) plays a role in defence against hemibiotrophic pathogens
      mediated by salicylate (SA) and also necrotrophic pathogens influenced by
      jasmonate/ethylene (JA/Et). This study examined how NO-oxidizing haemoglobins
      (Hb) encoded by GLB1, GLB2, and GLB3 in Arabidopsis could influence both defence
      pathways. The impact of Hb on responses to the hemibiotrophic Pseudomonas
      syringae pathovar tomato (Pst) AvrRpm1 and the necrotrophic Botrytis cinerea were
      investigated using glb1, glb2, and glb3 mutant lines and also CaMV 35S GLB1 and
      GLB2 overexpression lines. In glb1, but not glb2 and glb3, increased resistance
      was observed to both pathogens but was compromised in the 35S-GLB1. A quantum
      cascade laser-based sensor measured elevated NO production in glb1 infected with
      Pst AvrRpm1 and B. cinerea, which was reduced in 35S-GLB1 compared to Col-0. SA
      accumulation was increased in glb1 and reduced in 35S-GLB1 compared to controls
      following attack by Pst AvrRpm1. Similarly, JA and Et levels were increased in
      glb1 but decreased in 35S-GLB1 in response to attack by B. cinerea. Quantitative
      PCR assays indicated reduced GLB1 expression during challenge with either
      pathogen, thus this may elevate NO concentration and promote a wide-ranging
      defence against pathogens.

PMID- 22641425
TI  - Comparative DFT study of N2 and NO adsorption on vanadium clusters V(n) (n = 2
      13).
AB  - Using gradient-corrected density functional theory, we have comparatively studied
      the adsorption properties of diatomic molecules N(2) and NO on vanadium clusters
      up to 13 atoms. Spontaneous dissociation is found for N(2) adsorbing on V(n) with
      n = 4-6, 12, and for NO with n = 3-12, respectively, whereas for the rest of the
      clusters, N(2) (NO) molecularly adsorbs on the cluster for all the possible
      sites. The incoming N(2) retains the magnetism of V(n) except for V(2) and V(6)
      whose moments are quenched from 2 MU(B) to zero. Consequently, the moments of
      V(n)N(2) (n = 2-13) show even/odd oscillation between 0 and 1 MU(B). On the
      adsorption of NO, the magnetic moments of V(n) with closed electronic shell are
      raised to 1 MU(B) at n = 4, 8, and 10, and 3 MU(B) at n = 12, whereas for open
      shell clusters, their magnetic moments increase for n = 5 and 9 and decrease for
      n = 2, 3, 5-7, 11, and 13 by 1 MU(B). These findings are rationalized by
      combinatory analysis from several aspects, for example, the geometry and
      stability of bare clusters, charge transfer induced by the adsorption, feature of
      frontier orbitals, and spin density distribution.

PMID- 22641426
TI  - Hemoglobin level and survival in hemodialysis patients with polycystic kidney
      disease and the role of administered erythropoietin.
AB  - Interventional trials indicate adverse outcomes when hemoglobin >13 g/dL is
      targeted in patients with chronic kidney disease (CKD) who receive erythropoiesis
      stimulating agents (ESAs). It is not clear whether high-achieved hemoglobin with
      minimal to no ESA administration as observed in some patients with polycystic
      kidney disease (PKD) is also associated with poor outcomes. Survival models were
      examined to assess the association between hemoglobin increments and mortality in
      a 6-year cohort of 2,402 PKD and 110,875 non-PKD hemodialysis patients across
      infrequent versus frequent ESA therapy defined as ESA < 25% of cohort time versus
      otherwise, respectively. Mortality risk was estimated by Cox proportional
      regression [hazard ratio (HR) and 95% of confidence interval] analysis. Patients
      with PKD were aged 58 +/- 13 years and included 46% women 14% Blacks,
      respectively. Fully adjusted death HRs of time-averaged hemoglobin increments
      <11.0, 12.0 to <13.0 g/dL (reference: 11.0 to <12.0 g/dL) for frequent ESA
      therapy were 2.57 (1.48-4.48), 0.60 (0.43-0.82), and 0.81 (0.50-1.29), whereas
      for infrequent ESA therapy they were 1.33 (0.47-3.78), 0.28 (0.13-0.61), and 0.22
      (0.09-0.57), respectively. Hence, in patients with PKD who require infrequent
      ESA, incrementally higher achieved hemoglobin including > 13.0 g/dL exhibits
      better survival; this incremental survival gain of higher hemoglobin is not
      observed in patients with PKD receiving frequent ESA administration, in whom
      hemoglobin concentration > 13 exhibits increased mortality.

PMID- 22641427
TI  - Effect of aloe polysaccharide on caspase-3 expression following cerebral ischemia
      and reperfusion injury in rats.
AB  - Stroke is a leading cause of cardiovascular morbidity, economic and social burden
      and mortality. Novel approaches are needed to address stroke prevention and
      treatment. The purpose of this study was to explore the effects of aloe
      polysaccharide on caspase-3 expression following cerebral ischemia reperfusion
      injury in rats. Male Wistar rats were randomly divided into 5 groups (16 rats in
      each group): aloe polysaccharide, ginkgo leaf tablet, nimodipine, model and sham
      surgery groups. The rats were administered the appropriate drug or normal saline
      for 7 days by gavage. A rat model of cerebral ischemia and reperfusion injury was
      established using the middle cerebral artery occlusion (MCAO) model. Caspase-3
      protein and mRNA expression levels in the cerebral cortex were detected by
      immunohistochemistry and reverse transcription-polymerase chain reaction (RT
      PCR), respectively. Results showed that caspase-3 protein and mRNA expression
      levels in the cerebral cortex in the aloe polysaccharide, ginkgo leaf tablet and
      nimodipine groups were significantly lower compared with the model group and were
      higher than the sham surgery group (P<0.05). No significant difference was
      observed in caspase-3 protein and mRNA expression among the aloe polysaccharide,
      the ginkgo leaf tablet and the nimodipine groups (P>0.05). In conclusion, aloe
      polysaccharide has a protective effect on cerebral ischemia that may be due to
      the inhibition of neuronal cell apoptosis.

PMID- 22641428
TI  - The core stimulon of Corynebacterium pseudotuberculosis strain 1002 identified
      using ab initio methodologies.
AB  - Corynebacterium pseudotuberculosis is a bacterium which causes diseases such as
      caseous lymphadenitis in small ruminants, resulting in large-scale economic
      losses for agribusiness worldwide. Consequently, this bacterium including its
      transcriptional profile analysis has been the focus of various studies.
      Identification of the transcripts that appear under conditions that simulate the
      environment encountered by this bacterial species in the host is of great
      importance in discovering new targets for the production of more efficient
      vaccines. We sequenced the cDNA of Corynebacterium pseudotuberculosis strain
      1002, using the SOLiD V3 system, under the following conditions: osmotic stress
      (2 M), acidity (pH), heat shock (50  degrees C) and control condition (N). To
      identify the transcripts shared among the stimulons and integrate this
      information with the results from BLAST and BLAST2GO, we developed the software
      CoreStImulon (CSI) which allows the user to individually distinguish the genes in
      terms of their participation in biological processes, their function and cellular
      location. In the biosynthetic processes, eleven genes represented in the core
      stimulon and twenty genes in the control were observed. This validates the
      hypothesis that the organisms strategy for surviving in a hostile environment is
      through growth reduction. The oxidation reduction process, response to stress
      process, and cell adhesion are controlled by genes that contribute to bacterial
      cell maintenance under stress conditions; these could be involved in their
      pathogenicity. The methodology for identification of transcripts obtained by ab
      initio assembly and shared among the stimulons permitted candidates selection for
      vaccine studies. CSI is available at
      https://sourceforge.net/projects/corestimulon/.

PMID- 22641429
TI  - Gibberellic acid induces alpha-amylase expression in adipose-derived stem cells.
AB  - Salivary alpha-amylase is the most important enzyme for oral digestion of dietary
      starch. Therefore, regeneration of the salivary glands via a tissue engineering
      approach is clearly required for patients with salivary gland dysfunction. Early
      during seed germination, the embryo synthesizes gibberellic acid (GA3), a plant
      hormone that activates the synthesis and secretion of alpha-amylase. The purpose
      of this study was to explore an approach for differentiation of stem cells into
      salivary glands using GA3. We isolated adipose-derived stem cells (ASCs), which
      are positive for mesenchymal stem cell markers (CD73, CD90 and CD105) and possess
      pluripotency to osteoblasts, adipocytes and neural cells, from human buccal fat
      pads, which are a readily available source for dentists and oral surgeons. In
      addition, we investigated the cytotoxicity of GA3 for human ASCs. GA3 neither
      affects cell morphology nor cell viability in a dose- or time-dependent manner.
      ASCs were incubated with GA3 to assess mRNA and protein expression of alpha
      amylase by reverse transcriptase-polymerase chain reaction and western blot
      analyses. alpha-amylase mRNA expression on 21 days after treatment with GA3 (1
      mM) was seven times greater than that in resting condition (Day 0). While we did
      not detect alpha-amylase bands on Day 0, alpha-amylase protein was detectable 7
      days after treatment with GA3, reaching a maximal level on Day 21. Our results
      indicated that GA3 can increase cellular alpha-amylase expression and that our
      induction method would be useful for therapeutic application for salivary gland
      regeneration.

PMID- 22641430
TI  - Mechanism of cellular uptake of graphene oxide studied by surface-enhanced Raman
      spectroscopy.
AB  - The last few years have witnessed rapid development of biological and medical
      applications of graphene oxide (GO), such as drug/gene delivery, biosensing, and
      bioimaging. However, little is known about the cellular uptake mechanism and
      pathway of GO. In this work, surface-enhanced Raman scattering (SERS)
      spectroscopy is employed to investigate the cellular internalization of GO loaded
      with Au nanoparticles (NPs) by Ca Ski cells. The presence of Au NPs on the
      surface of GO enables detection of enhanced intrinsic Raman signals of GO inside
      the cell. The SERS results reveal that GO is distributed inhomogeneously inside
      the cell. Furthermore, internalization of Au-GO into Ca Ski cells is mainly via
      clathrin-mediated endocytosis, and is an energy-dependent process.

PMID- 22641431
TI  - Changes in genotypes of Plasmodium falciparum human malaria parasite following
      withdrawal of chloroquine in Tiwi, Kenya.
AB  - Chloroquine (CQ) drug was withdrawn in 1998 as a first-line treatment of
      uncomplicated malaria in Kenya. This was in response to resistance to the drug in
      Plasmodium falciparum malaria parasite. Investigations were conducted to
      determine prevalence of CQ resistance genotypes in the parasites in Tiwi, a
      malaria endemic town in Kenya, before and about a decade after the withdrawal of
      the drug. Blood samples were collected and spotted on filter papers in 1999 and
      2008 from 75 and 77 out-patients respectively with uncomplicated malaria. The
      sampling was conducted using finger pricking technique. DNA was extracted from
      individual spots in the papers and screened for the presence of P. falciparum
      chloroquine resistance transporter (Pfcrt) and multi drug resistance (Pfmdr-1)
      markers using nested PCR. Nature of mutations (haplotypes) in the Pfcrt and Pfmdr
      1 markers in the samples were confirmed using dot blot hybridization technique.
      Changes in pattern of CQ resistance in the parasite samples in 1999 and 2008 were
      assessed by Chi Square test. There was a significant (P<0.05) reduction in CQ
      resistant genotypes of the parasite between 1999 and 2008. Pfmdr and Pfcrt CQ
      resistant genotypes in 2008 reduced to 54.10 and 63.64% respectively, from 75.39
      and 88.0% respectively in 1999. This reduction was accompanied by emergence of
      Pfcrt specific CQ sensitive (IEK) and intermediate/partially CQ resistant (MET)
      haplotypes. Results suggest significant reversal of the phenotype of the parasite
      from chloroquine resistant to wild/sensitive type. The novel haplotypes indicates
      transitional phase of the parasite to the wild type. Current prevalence of
      chloroquine resistant genotype is definitely above the threshold for efficacious
      re-introduction of chloroquine for treatment of malaria in Tiwi.

PMID- 22641432
TI  - 'Smoking' mephedrone: the identification of the pyrolysis products of 4
      methylmethcathinone hydrochloride.
AB  - The ring-substituted cathinone - mephedrone - has gained popularity among
      recreational drug users over the past several years. It is generally consumed
      orally or by snorting but reports indicate that it is also ingested by
      vaporization/inhalation. This study examines the pyrolysis products produced by
      heating mephedrone under using simulated 'meth pipe' conditions. Thirteen
      pyrolysis products were identified, the major ones being iso-mephedrone, 4
      methylpropiophenone, 4-methylphenylacetone, two pyrazine derivatives formed by
      dimerization of mephedrone, N-methylated mephedrone (N,N,4-trimethylcatinone),
      two hydroxylated oxidation products and a diketone. Other minor products formed
      were identified as 4-methylacetophenone, two alpha-chloro ketones and N
      methylated iso-mephedrone.

PMID- 22641433
TI  - Waterpipe smoking among U.S. university students.
AB  - INTRODUCTION: While cigarette use is declining, smoking tobacco with a waterpipe
      is an emerging trend. We aimed to determine the prevalence of waterpipe use in a
      large diverse sample of U.S. university students and to assess the association of
      waterpipe use with individual and institution-related characteristics. METHODS:
      We assessed students from 152 U.S. universities participating in the National
      College Health Assessment during 2008-2009. We used multivariable regression
      models to determine independent associations between individual and institutional
      characteristics and waterpipe tobacco use in the past 30 days and ever. RESULTS:
      Of 105,012 respondents included in the analysis, most were female (65.7%), White
      (71.2%), and attending public (59.7%) nonreligious (83.1%) institutions. Mean age
      was 22.1 years. A total of 32,013 (30.5%) reported ever using a waterpipe to
      smoke tobacco. Rates for current tobacco use were 8.4% for waterpipes, 16.8% for
      cigarettes, 7.4% for cigars (including cigarillos), and 3.5% for smokeless
      tobacco. Of current waterpipe users, 51.4% were not current cigarette smokers.
      Although current waterpipe use was reported across all individual and
      institutional characteristics, fully adjusted multivariable models showed that it
      was most strongly associated with younger age, male gender, White race,
      fraternity/sorority membership, and nonreligious institutions in large cities in
      the western United States. CONCLUSIONS: After cigarettes, waterpipe use was the
      most common form of tobacco use among university students. Because waterpipe use
      affects groups with a wide variety of individual and institutional
      characteristics, it should be included with other forms of tobacco in efforts
      related to tobacco surveillance and intervention.

PMID- 22641434
TI  - Autologous stem cell transplant for light chain deposition disease: incorporating
      bortezomib to the induction therapy.

PMID- 22641435
TI  - Standardized information for living liver donors.

PMID- 22641436
TI  - Modified ART: why not?

PMID- 22641437
TI  - Does the casting mode influence microstructure, fracture and properties of
      different metal ceramic alloys?
AB  - The aim of the present study was to evaluate the tensile strength, elongation,
      microhardness, microstructure and fracture pattern of various metal ceramic
      alloys cast under different casting conditions. Two Ni-Cr alloys, Co-Cr and Pd-Ag
      were used. The casting conditions were as follows: electromagnetic induction
      under argon atmosphere, vacuum, using blowtorch without atmosphere control. For
      each condition, 16 specimens, each measuring 25 mm long and 2.5 mm in diameter,
      were obtained. Ultimate tensile strength (UTS) and elongation (EL) tests were
      performed using a Kratos machine. Vickers Microhardness (VM), fracture mode and
      microstructure were analyzed by SEM. UTS, EL and VM data were statistically
      analyzed using ANOVA. For UTS, alloy composition had a direct influence on
      casting condition of alloys (Wiron 99 and Remanium CD), with higher values shown
      when cast with Flame/Air (p < 0.05). The factors 'alloy" and 'casting condition"
      influenced the EL and VM results, generally presenting opposite results, i.e.,
      alloy with high elongation value had lower hardness (Wiron 99), and casting
      condition with the lowest EL values had the highest VM values (blowtorch). Both
      factors had significant influence on the properties evaluated, and prosthetic
      laboratories should select the appropriate casting method for each alloy
      composition to obtain the desired property.

PMID- 22641438
TI  - Photoelastic evaluation of the effect of composite formulation on polymerization
      shrinkage stress.
AB  - We compared polymerization stress in two commercial composites and three
      experimental composites made using camphorquinone (CQ) and/or phenylpropanedione
      (PPD) as photoinitiators. The internal surfaces of photoelastic resin discs with
      cylindrical cavities were roughened and treated with adhesive. Composites were
      divided into five groups: two commercial composites (Filtek Silorane and Filtek
      Z250) and three experimental composites with CQ/amine, CQ/PPD/amine, and
      PPD/amine. Composites were photopolymerized inside cavities, and subjected to
      photoelastic analysis immediately and at 24 hours and 7 days later using a plane
      polariscope. Stress created by Silorane (3.08 +/- 0.09 MPa) was similar to that
      of Z250 (3.19 +/- 0.13 MPa) immediately after photopolymerization (p > 0.05).
      After 24 hours and 7 days, Z250 (3.53 +/- 0.15 and 3.69 +/- 0.10 MPa,
      respectively) showed higher stress than Silorane (3.19 +/- 0.10 and 3.16 +/- 0.10
      MPa, respectively). Qualitative analysis immediately after photopolymerization
      showed composite/CQ promoted higher stress than PPD, but stress levels at other
      evaluated times were statistically similar, varying between 3.45 +/- 0.11 MPa and
      3.92 +/- 0.13 MPa. At 24 hours and 7 days, Silorane created the lowest stress.
      All photoinitiators created comparable tensions during polymerization.

PMID- 22641439
TI  - The influence of mouthrinses and simulated toothbrushing on the surface roughness
      of a nanofilled composite resin.
AB  - The aim of this study was to determine the influence of mouthrinses on the
      surface roughness of a nanofilled composite resin after toothbrushing. One
      hundred nanofilled composite resin specimens were prepared and randomly
      distributed into two groups-brushed and non-brushed-and then assigned to five
      subgroups, according to the mouthrinse solutions (n = 10): Colgate Plax Fresh
      Mint, Oral B, Cepacol, Colgate Plax, and artificial saliva. Each sample was
      immersed in 20 mL of the mouthrinses for 1 minute, 5 days per week, twice a day,
      for a 3-week period. The control group used in the study was one in which the
      specimens were not subjected to brushing and remained only in artificial saliva.
      Toothbrushing was performed once a week for 1 minute, for 3 weeks. Surface
      roughness measurements (Ra) were performed after the immersion period and
      toothbrushing, by means of a profilometer. Data were analyzed by two-way ANOVA
      and Tukey's test. Analysis revealed that the association between toothbrushing
      and Colgate Plax Fresh Mint produced the lowest surface roughness (p < 0.05). All
      other groups tested (Oral B, Cepacol, Colgate Plax, artificial saliva) exhibited
      no statistically significant differences between surfaces, whether subjected to
      toothbrushing or not (p < 0.05). It was concluded that the surface roughness of
      the nanofilled composite resin tested can be influenced by the mouthrinse
      associated with toothbrushing.

PMID- 22641440
TI  - In vitro evaluation of the root canal cleaning ability of plant extracts and
      their antimicrobial action.
AB  - This in vitro study evaluated both the antimicrobial activity and the root canal
      cleaning ability of plant extracts used in irrigation solutions. The
      antimicrobial activities of the aroeira-da-praia (Schinus terebintifolius Raddi)
      and the quixabeira (Syderoxylum obtusifolium Roem & Schult) hydroalcoholic
      extracts, of 2.5% sodium hypochlorite (NaOCl) and of 0.12% chlorhexidine
      (positive control) against Enterococcus faecalis were tested with the agar well
      diffusion method. The level of root canal cleanliness was examined by scanning
      electron microscopy (SEM). Twenty one single-rooted human teeth were divided into
      three groups according to the irrigation solution applied: 1) 50% aroeira-da
      praia; 2) 50% quixabeira and 3) a combination of 2.5% sodium hypochlorite + 17%
      EDTA. All solutions tested demonstrated antimicrobial activity against
      Enterococcus faecalis. The SEM analysis revealed that higher and lower degrees of
      surface cleaning were observed, in the three groups, respectively for the coronal
      and apical thirds, in that quixabeira showed the greatest efficiency in removing
      the smear layer in the apical third. All the agents tested presented
      antimicrobial activity against E. faecalis. None, however, was able to completely
      remove the smear layer of the dentinal surface in the different thirds of the
      root canal. The results suggest that the analyzed plant extracts may represent a
      new therapeutic option in the list of alternative agents available for endodontic
      treatment.

PMID- 22641441
TI  - Assessing apical transportation in curved canals: comparison between cross
      sections and micro-computed tomography.
AB  - The aim of this study was to compare two methods of assessing apical
      transportation in curved canals after rotary instrumentation, namely, cross
      sections and micro-computed tomography (uCT). Thirty mandibular molars were
      divided into two groups and prepared according to the requirements of each
      method. In G1 (cross-sections), teeth were embedded in resin blocks and sectioned
      at 2.0, 3.5, and 5.0 mm from the anatomic apex. Pre- and postoperative sections
      were photographed and analyzed. In G2 (uCT), teeth were embedded in a rubber-base
      impression material and scanned before and after instrumentation. Mesiobuccal
      canals were instrumented with the Twisted File (TF) system (SybronEndo, Orange,
      USA), and mesiolingual canals, with the EndoSequence (ES) system (Brasseler,
      Savannah, USA). Images were reconstructed, and sections corresponding to
      distances 2.0, 3.5, and 5.0 mm from the anatomic apex were selected for
      comparison. Data were analyzed using Mann-Whitney's test at a 5% significance
      level. The TF and ES instruments produced little deviation from the root canal
      center, with no statistical difference between them (P > 0.05). The canal
      transportation results were significantly lower (0.056 mm) in G2 than in G1
      (0.089 mm) (p = 0.0012). The uCT method was superior to the cross-section method,
      especially in view of its ability to preserve specimens and provide results that
      are more closely related to clinical situations.

PMID- 22641442
TI  - Coexpression of p53 and Ki 67 and lack of c-erbB2 expression in oral leukoplakias
      in India.
AB  - Oral cancer is commonly preceded by premalignant lesions and conditions. The
      clinician's ability to identify lesions at an increased risk of cancer
      development is critical for its control. The purpose of this study was to compare
      the expression of tumor suppressor gene p53, proliferation marker Ki-67, and
      oncogene c-erbB2 and to evaluate the relevance of their co-expression in the
      diagnosis of, and prognosis for, oral leukoplakia. In the present study, the
      expression of biomarkers was studied immunohistochemically in 55 cases of
      leukoplakia (26 without dysplasia, 29 with dysplasia) and 10 cases of normal
      epithelia. The Labeling Indices (LI) of p53 and Ki-67 were found to increase
      significantly with an increase in the grade of dysplasia. A significant
      correlation was also found between the LI of p53 and that of Ki-67. It was also
      observed that c-erbB2 expression was only cytoplasmic, indicating incomplete
      receptor degradation. Hence, it can be concluded from the present study that the
      increased expression of p53 and Ki-67 with an increase in the grade of dysplasia
      suggests that their co-expression may be used for the identification of high-risk
      lesions. Also, c-erbB2 has no pathogenetic role in early carcinogenesis in the
      studied population, although incomplete receptor degradation, as evidenced by
      cytoplasmic staining, may indicate an early change.

PMID- 22641443
TI  - A 10-year study of specimens submitted to oral pathology laboratory analysis:
      lesion occurrence and demographic features.
AB  - The purpose of the present paper was to describe the range of lesions
      histologically diagnosed in an oral pathology laboratory in southern Brazil. A
      retrospective study of 8,168 specimen analyses recorded between 1995 and 2004 was
      conducted. The records were retrieved from the Oral Pathology Laboratory, School
      of Dentistry, Federal University of Rio Grande do Sul, RS, Brazil. A total of
      6,831 valid cases (83.63%) were examined. Of these, inflammatory lesions were the
      most common occurrences (n = 4,320; 63.24%). Benign and malignant tumors
      accounted for 7.66% (n = 523) and 1.9% (n = 130) of the occurrences,
      respectively. Significant associations were observed between nonneoplastic
      proliferative disorders and benign mesenchymal tumors in females, and between
      squamous cell carcinoma and leukoplakia in males. Most diagnoses were benign in
      nature and had an inflammatory etiology. The association of some demographic
      characteristics with the occurrence of lesions suggests that these
      characteristics should be considered in performing differential diagnoses.

PMID- 22641444
TI  - Rapid palatal expansion: a comparison of two appliances.
AB  - This study analyzed occlusal radiographs to compare the transverse changes
      produced in patients treated with rapid maxillary expansion using two types of
      appliances. The sample consisted of 31 children aged 7 to 10.6 years, of both
      genders, with posterior cross-bite. Fifteen children were treated with a tooth
      borne expander and 16 were treated with a tooth-tissue-borne expander. Occlusal
      radiographs obtained at treatment onset and at the end of the retention period
      were digitized. The following variables were measured: intermolar distance (IMD),
      interapical distance (IApD), interbase distance (IBaD) and interarm distance
      (IArD). The results revealed increases in all measurements in both groups after
      rapid maxillary expansion. Comparison between groups revealed that the increases
      were greater in patients treated with the tooth-borne expander, except for the
      IArD measurement, which presented the same increase in both groups. Even though
      the IMD measurements differed between expanders, they were proportional to the
      activation of the appliances (IBaD). The increase in the IApD measurement was
      proportionally greater in the group treated with the tooth-borne expander
      (0.7:1.0) than in that treated with the tooth-tissue-borne expander (0.4:1.0). It
      was concluded that both appliances had similar effects, although the tooth-tissue
      borne expander produced a lesser opening at the apical region of the incisors.

PMID- 22641445
TI  - Impact of adhesive and photoactivation method on sealant integrity and polymer
      network formation.
AB  - We evaluated the influence of photoactivation method and hydrophobic resin (HR)
      application on the marginal and internal adaptation, hardness (KHN), and
      crosslink density (CLD) of a resin-based fissure sealant. Model fissures were
      created in bovine enamel fragments (n = 10) and sealed using one of the following
      protocols: no adhesive system + photoactivation of the sealant using continuous
      light (CL), no adhesive system + photoactivation of the sealant using the soft
      start method (SS), HR + CL, or HR + SS. Marginal and internal gaps and KHN were
      assessed after storage in water for 24 h. The CLD was indirectly assessed by
      repeating the KHN measurement after 24 h of immersion in 100% ethanol. There was
      no difference among the samples with regard to marginal or internal adaptation.
      The KHN and CLD were similar for samples cured using either photoactivation
      method. Use of a hydrophobic resin prior to placement of fissure sealants and
      curing the sealant using the soft-start method may not provide any positive
      influence on integrity or crosslink density.

PMID- 22641446
TI  - Effect of Er,Cr:YSGG and Er:YAG laser irradiation on the adhesion of blood
      components on the root surface and on root morphology.
AB  - The aim of this study was to conduct an in vitro evaluation, by scanning electron
      microscopy (SEM), of the adhesion of blood components on root surfaces irradiated
      with Er,Cr:YSGG (2.78 um) or Er:YAG (2.94 um) laser, and of the irradiation
      effects on root surface morphology. Sixty samples of human teeth were previously
      scaled with manual instruments and divided into three groups of 20 samples each:
      G1 (control group) - no treatment; G2 - Er,Cr:YSGG laser irradiation; G3 - Er:YAG
      laser irradiation. After performing these treatments, blood tissue was applied to
      10 samples of each group, whereas 10 samples received no blood tissue
      application. After performing the laboratory treatments, the samples were
      observed under SEM, and the resulting photomicrographs were classified according
      to a blood component adhesion scoring system and root morphology. The results
      were analyzed statistically (Kruskall-Wallis and Mann Whitney tests, alpha= 5%).
      The root surfaces irradiated with Er:YAG and Er,Cr:YSGG lasers presented greater
      roughness than those in the control group. Regarding blood component adhesion,
      the results showed a lower degree of adhesion in G2 than in G1 and G3 (G1 * G2: p
      = 0.002; G3 * G2: p = 0.017). The Er:YAG and Er,Cr:YSGG laser treatments caused
      more extensive root surface changes. The Er:YAG laser treatment promoted a
      greater degree of blood component adhesion to root surfaces, compared to the
      Er,Cr:YSGG treatment.

PMID- 22641447
TI  - Desensitizing treatments for dentin hypersensitivity: a randomized, split-mouth
      clinical trial.
AB  - The aim of this randomized, controlled, split-mouth, clinical study was to
      differentiate and clinically qualify the effectiveness of different desensitizing
      agents in the treatment of painful symptoms caused by cervical dentin
      hypersensitivity (CDH). Two hundred-and-fifty-two teeth of 42 patients were
      distributed into seven groups (n = 36): G1 - placebo; G2, G3, G4 and G6 -
      fluoride varnishes; G5 - sodium fluoride; G7 - potassium oxalate. Three
      applications were made one week apart. A three-score system (Alfa = 0, Bravo = 2,
      and Charlie = 3, respectively for no sensitivity, slight sensitivity and high
      sensitivity) was used to assess CDH after each application and after 30 days. The
      data were subjected to statistical analysis using the Kruskall-Wallis and Dun
      tests. After the second week, statistically significant differences were observed
      for all materials compared with the baseline. After 30 days, Group G7 had
      presented a significant gradual reduction along all the evaluated time intervals.
      It was concluded that all the desensitizing agents were capable of reducing
      dentin hypersensitivity, with the exception of the placebo and the sodium
      fluoride groups.

PMID- 22641448
TI  - In vitro evaluation of the whitening effect of mouth rinses containing hydrogen
      peroxide.
AB  - The aim of this study was to evaluate the bleaching effect of two mouth rinses
      containing hydrogen peroxide. Thirty premolars were randomly divided into two
      groups (n = 15): Listerine Whitening (LW) and Colgate Plax Whitening (PW). The
      teeth were fixed on a wax plate and with acrylic resin, at a distance of 5 mm
      between each other, exposing the buccal surfaces. All teeth were stored in
      artificial saliva for 45 days, being removed twice a day to be immersed for 1 min
      in each mouthwash, followed by 10-second washing in tap water. The pH of each
      product was measured. Digital images of each tooth were captured under
      standardized conditions. These images were cut in areas previously demarcated and
      analyzed in Adobe Photoshop 7.0 using the CIEL*a*b* color space system. Data were
      statistically analyzed by a paired t test and an independent samples t test (p <
      0.05). The pH values were 5.6 and 3.4 for LW and PW, respectively. Both treatment
      groups showed a decrease in the b* parameter (p < 0.01), but a decrease of a* was
      observed only for PW (p < 0.01). While the LW group showed an improvement in
      lightness (L*) (p = 0.03), the PW group had a decrease in the L* parameter (p =
      0.02). Within the limitations of this study, it is possible to conclude that both
      products caused some degree of whitening; however, extreme care should be taken
      when using Colgate Plax Whitening, since its decline in luminosity might be due
      to its lower pH.

PMID- 22641449
TI  - Bonding to dentin as a function of air-stream temperatures for solvent
      evaporation.
AB  - This study evaluated the influence of solvent evaporation conditions of acid
      etching adhesives. The medium dentin of thirty extracted human third molars was
      exposed and bonded to different types of etch-and-rinse adhesives: 1) Scotchbond
      Multi-Purpose (SBMP) ; water-based; 2) Adper Single Bond 2 (SB) ; ethanol/water
      based, and 3) Prime & Bond 2.1 (PB) ; acetone-based. Solvents were evaporated at
      air-drying temperatures of 21oC or 38oC. Composite buildups were incrementally
      constructed. After storage in water for 24 h at 37oC, the specimens were prepared
      for bond strength testing. Data were analyzed by two-way ANOVA and Tukey's test
      (5%). SBMP performed better when the solvents were evaporated at a higher
      temperature (p < 0.05). Higher temperatures did not affect the performance of SB
      or PB. Bond strength at room temperature was material-dependent, and air-drying
      temperatures affected bonding of the water-based, acid-etching adhesive.

PMID- 22641450
TI  - Nanocrystalline NiMoO4 with an ordered mesoporous morphology as potential
      material for rechargeable thin film lithium batteries.
AB  - Nanocrystalline nickel molybdate (NiMoO(4)) thin film electrodes with a 3D
      honeycomb structure of uniform 17 nm diameter pores were successfully produced
      through facile polymer templating strategies. These novel sol-gel type materials
      exhibit enhanced lithium ion storage capabilities, and thus show promise for
      battery applications.

PMID- 22641451
TI  - Platelet mimetic particles for targeting thrombi in flowing blood.

PMID- 22641452
TI  - Strain-induced structural transformation of a silver nanowire.
AB  - We have investigated the structural characteristics of the experimentally 
      observed phase transition of a silver nanowire into a tube under tensile strain.
      In the simulations, atoms are allowed to interact via a model potential extracted
      from the modified embedded atom method. Our calculations demonstrate that the
      formation of the hollow structure is governed by the nature of the applied
      strain, the length of the wire, and the initial cross-sectional shape. The
      results further offer insights into the atomistic nature of this specific
      structural transformation into a nanotube with the smallest possible cross
      section.

PMID- 22641453
TI  - CORAL: QSPR modeling of rate constants of reactions between organic aromatic
      pollutants and hydroxyl radical.
AB  - The rate constants (K(OH)) of reactions between 78 organic aromatic pollutants
      and hydroxyl radical were examined. Simplified molecular input line entry system
      was used as representation of the molecular structure of the pollutants.
      Quantitative structure-property relationships was developed using CORAL software
      (http://www.insilico.eu/CORAL) for four random splits of the data into the
      subtraining, calibration, and test sets. The obtained results reveal good
      predictive potential of the applied approach: correlation coefficients (r(2)) for
      the test sets of the four random splits are 0.75, 0.91, 0.84, and 0.80. Using the
      Monte Carlo method CORAL software generated the optimal descriptors for one
      variable models. The reproducibility of each model was tested performing three
      runs of the Monte Carlo optimization. The current data were compared to previous
      results and discussed.

PMID- 22641455
TI  - Diffuse pattern of bone marrow involvement on magnetic resonance imaging is
      associated with high risk cytogenetics and poor outcome in newly diagnosed,
      symptomatic patients with multiple myeloma: a single center experience on 228
      patients.
AB  - Magnetic Resonance Imaging (MRI) and specific cytogenetic abnormalities offer
      important prognostic information for myeloma patients. However, limited data are
      available about the association between cytogenetic abnormalities and MRI
      patterns of marrow infiltration. To address this issue, we analyzed 228
      consecutive newly diagnosed, symptomatic patients who were diagnosed and treated
      in a single center. On bone marrow MR images, 95 (41%) patients had diffuse, 94
      (41%) had focal, 35 (15%) were normal, and 4 (1.7%) patients had variegated
      pattern of marrow infiltration. High risk cytogenetics were more commonly
      observed with diffuse MRI pattern (50% vs. 31% in focal and normal patterns).
      Patients with diffuse MRI pattern had poorer survival compared to others and
      responded better to novel agent-based therapies than to conventional chemotherapy
      (objective response: 88% vs. 46%, P < 0.001). There was a significant improvement
      of patients' survival with a diffuse MRI pattern when treated upfront with novel
      agents compared to conventional chemotherapy (47 vs. 24 months; P < 0.001).
      Diffuse MRI pattern along with ISS-3 and high risk cytogenetics could identify a
      very high risk group of patients with extremely poor median survival (21 months)
      and an only 35% probability of 3-year OS. Our study shows that symptomatic
      myeloma patients with a diffuse MRI pattern at diagnosis very often show high
      risk cytogenetic abnormalities and are benefiting from upfront novel agent-based
      therapies. Diffuse MRI pattern in combination with high risk cytogenetics and ISS
      3 can identify a subset of myeloma patients with very poor prognosis who may need
      innovative treatment strategies and possibly more aggressive therapies.

PMID- 22641456
TI  - Involvement of TL1A and DR3 in induction of ischaemia and inflammation in urinary
      bladder dysfunction in the elderly.
AB  - Benign prostatic hyperplasia often causes intravesical obstruction in elderly
      men; however, the processes of aging and bladder outlet obstruction independently
      evoke alterations in the structure and function of the bladder. These changes
      lead to lower urinary tract symptoms; however, it is difficult to separate the
      effects of prostatic obstruction on the bladder from those of aging.
      Nevertheless, few studies have focused on elucidating the pathophysiological
      mechanisms in the aged bladder. Bladder dysfunction due to detrusor instability
      (caused by old age) is considered to be associated with chronic ischaemia and
      inflammation. The aim of this study was to explore the role of tumour necrosis
      factor (TNF)-like ligand 1A (TL1A) and death-domain receptor (DR)3 in the
      ischaemic and inflammatory process of aged bladder dysfunction. Sixteen bladder
      tissue samples collected from patients with urothelial tumours of the bladder
      were divided into two groups according to age: group 1 (controls, n=8) and group
      2 (aged group, n=8). Urodynamic examinations were preformed before radical
      cystectomy. The full-thickness bladder tissues were obtained at least 5 cm away
      from the margin of the tumours. The mRNA expression levels of TL1A, DR3, von
      Willebrand factor (vWF), interleukin (IL)-6 and nerve growth factor (NGF) in the
      two groups were determined using real-time reverse transcription-PCR and the
      protein expression levels of TL1A, DR3 and p65 were determined by western blot
      analysis. The TL1A and DR3 mRNA and protein expression levels of the aged
      bladders were upregulated compared to the control group (p<0.05). Compared to the
      control, the mRNA expression levels of vWF in the aged bladder tissues were
      markedly lower (p<0.01); however, the mRNA expression levels of IL-6 were
      significantly higher in the aged bladder tissues (p<0.01) compared to the
      control. No significant difference in NGF mRNA expression between the two groups
      was detected (p>0.05). In conclusion, the aged bladder was associated with
      ischaemic and inflammatory alterations in comparison to the control group. TL1A
      and DR3 may play an important role in the pathophysiological process of the aged
      bladder.

PMID- 22641457
TI  - Incidence of lymphoproliferative disorders in patients with celiac disease.
AB  - Prior studies describe an increased incidence of lymphoma in celiac disease.
      However, few studies differentiate among lymphoproliferative disorders (LPDs).
      Our aim was to determine incidences of LPD subtypes in celiac disease patients,
      describe patterns of celiac disease presentation in patients who develop LPD, and
      compare survival in patients with various LPD subtypes. We conducted a
      retrospective cohort study of adults with biopsy-proven celiac disease seen at a
      US referral center from 1981 to 2010, identified patients with comorbid LPD, and
      calculated standardized incidence ratios (SIR) for each LPD subtype. In our
      cohort of 1,285 patients with celiac disease, there were 40 patients with LPD
      [SIR = 6.48, 95% confidence interval (CI) = 4.62-8.64] including 33 with non
      Hodgkin lymphoma (NHL, SIR = 6.91, 95% CI = 4.26-8.28). The incidences of NHL
      subtypes including enteropathy-associated T-cell (EATL, n = 12), non-EATL T-cell
      (SIR = 22.43, 95% CI = 7.08-46.41), diffuse large B-cell (SIR = 5.37, 95% CI =
      1.93-10.52), mantle cell (SIR = 32.21, 95% CI = 6.07-78.97), and marginal zone
      (SIR = 37.17, 11.73-76.89) lymphoma remained significantly elevated when only
      those diagnosed with celiac before LPD were considered (n = 24, NHL SIR = 4.47,
      95% CI = 2.86-6.44). Patients who developed LPD were older at time of celiac
      disease diagnosis (57.9 +/- 15.5 versus 42.5 +/- 17.4 years, P < 0.0001) and more
      likely to present with diarrhea (60.0% versus 39.8% P = 0.016), abdominal pain
      (17.5% versus 5.5% P = 0.0046), and/or weight loss (12.5% versus 4.0%, P =
      0.028). EATL patients had a shorter average survival than non-EATL NHL patients
      (3.2 versus 15.0 years, P = 0.016). The incidence of LPD is increased in celiac
      disease patients. Those diagnosed later in life who present with symptoms of
      malabsorption are more likely to be diagnosed with LPD.

PMID- 22641458
TI  - Enrichment of neural-related genes in human mesenchymal stem cells from
      neuroblastoma patients.
AB  - Neuroblastoma (NB) is one of the most common pediatric solid tumors and, like
      most human cancers, is characterized by a broad variety of genomic alterations.
      Although mesenchymal stem cells (MSCs) are known to interact with cancer cells,
      the relationship between MSCs and metastatic NB cancer cells in bone marrow (BM)
      is unknown. To obtain genetic evidence about this interaction, we isolated BetaMU
      derived MSCs from children with NB and compared their global expression patterns
      with MSCs obtained from normal pediatric donors, using the Agilent 44K
      microarrays. Significance analysis of microarray results with a false discovery
      rate (FDR) <5% identified 496 differentially expressed genes showing either a 2
      fold upregulation or downregulation between both groups of samples. Comparison of
      gene ontology categories of differentially expressed genes revealed the
      upregulation of genes categorized as 'neurological system process', 'cell
      adhesion', 'apoptosis', 'cell surface receptor linked signal transduction',
      'intrinsic to membrane' and 'extracellular region'. Among the downregulated
      genes, several immunology-related terms were the most abundant. These findings
      provide preliminary genetic evidence of the interaction between MSCs and NB
      cancer cells in BetaMU as well as identify relevant biological processes
      potentially altered in MSCs in response to NB.

PMID- 22641459
TI  - Planar emulation of natural compound eyes.

PMID- 22641461
TI  - Organic materials for deep blue phosphorescent organic light-emitting diodes.
AB  - Recently, great progress has been made in the device performance of deep blue
      phosphorescent organic light-emitting diodes (PHOLEDs) by developing high triplet
      energy charge-transport materials, high triplet energy host and deep blue
      emitting phosphorescent dopant materials. A high quantum efficiency of over 25%
      and a high power efficiency of over 15 lm/W have already been achieved at 1000 cd
      m(-2) in the deep blue PHOLEDs with a y color coordinate less than 0.20. In this
      work, recent developments in organic materials for high efficiency deep blue
      PHOLEDs are reviewed and a future strategy for the development of high efficiency
      deep blue PHOLEDs is proposed.

PMID- 22641460
TI  - Posttransplant metabolic syndrome in children and adolescents after liver
      transplantation: a systematic review.
AB  - During long-term follow-up, 18% to 67% of pediatric liver transplant recipients
      are overweight or obese, with rates varying by age and pretransplant weight
      status. A similar prevalence of posttransplant obesity has been seen in adults.
      Adults also develop posttransplant metabolic syndrome and, consequently,
      cardiovascular disease at rates that exceed the rates in age- and sex-matched
      populations. Posttransplant metabolic syndrome has never been studied in
      pediatric liver transplant recipients, and this population is growing as
      transplant outcomes continue to improve. Here we systematically review the
      literature for each component of metabolic syndrome-obesity, hypertension,
      dyslipidemia, and glucose intolerance-in pediatric liver transplant recipients.
      Their rates of obesity are similar to the rates in children in the general U.S.
      population. However, hypertension, dyslipidemia, and diabetes are more common
      than would be expected in transplant recipients according to age, sex, and
      obesity severity. Immunosuppressive medications are major contributors. The
      limitations of previous studies, including heterogeneous methods of diagnosis,
      follow-up times, and immunosuppressive regimens, hinder the analysis of risk
      factors. Importantly, no studies have reported graft or patient outcomes
      associated with components of metabolic syndrome after pediatric liver
      transplantation. However, if the trends in children are similar to the trends
      seen in adults, these conditions may lead to significant long-term morbidity.
      Further research on the prevalence, causes, and consequences of posttransplant
      metabolic syndrome in pediatric liver transplant recipients is needed and will
      ultimately help to improve long-term outcomes.

PMID- 22641462
TI  - Gas-phase reactions of SiH(n)+ (n = 1,2) with NF3: a computational investigation
      on the detailed mechanistic aspects.
AB  - The mechanism of the gas-phase reactions of SiH(n)(+) (n = 1,2) with NF(3) were
      investigated by ab initio calculations at the MP2 and CAS-MCSCF level of theory.
      In the reaction of SiH(+), the kinetically relevant intermediates are the two
      isomeric forms of fluorine-coordinated intermediate HSi-F-NF(2)(+). These species
      arise from the exoergic attack of SiH(+) to one of the F atoms of NF(3) and
      undergo two competitive processes, namely an isomerization and subsequent
      dissociation into SiF(+) + HNF(2) , and a singlet-triplet crossing so to form the
      spin-forbidden products HSiF(+) + NF(2). The reaction of SiH(2)(+) with NF(3)
      involves instead the concomitant formation of the nitrogen-coordinated complex
      H(2)Si-NF(3)(+) and of the fluorine-coordinated complex H(2)Si-F-NF(2)(+). The
      latter isomer directly dissociates into NF(2)(+) + H(2)SiF, whereas the former
      species preferably undergoes the passage through a conical intersection point so
      to form a H(2) SiF-NF(2)(+) isomer, which eventually dissociates into H(2)SiF(+)
      and NF(2).

PMID- 22641463
TI  - A virtual source pattern method for fluorescence tomography with structured
      light.
AB  - In order to reduce both acquisition and reconstruction times, illumination and
      detection in fluorescence diffuse optical tomography (FDOT) have recently evolved
      from a point-based to a pattern-based approach. The use of structured
      illumination, offering the ability to project any pattern of light onto the
      object, associated with the compression of the acquired fluorescence images has
      paved the way for a new generation of fast reconstruction algorithms for FDOT.
      However, the choice of the most appropriate set of source patterns is still an
      open problem. Here, the use of typical source patterns is investigated on
      experimental data. Reconstructions of similar qualities are obtained for the
      different types of source patterns. We found that the performances of structured
      illumination are limited by the required positivity of the source patterns. To
      alleviate this problem, we introduce a novel method, namely the virtual source
      pattern method, which allows for considering any kind of patterns, e.g., with
      negative and complex intensities. This new method provides a significant increase
      of the contrast of the reconstruction and also a reduction of the reconstruction
      error, especially when virtual wavelet source patterns are considered.

PMID- 22641464
TI  - Development of a fluorescent chalcone library and its application in the
      discovery of a mouse embryonic stem cell probe.
AB  - We report the first fluorescent diamino-chalcone library and its application in
      the discovery of a mouse embryonic stem cell (mESC) probe. CDg4, a novel green
      fluorescent mESC probe was discovered through a high-content image based
      screening of 160 members of the chalcone library. Interestingly, the molecular
      binding target of CDg4 was identified as the glycogen of the stem cell colony
      surface, rather than a conventional protein target from an intracellular source.

PMID- 22641465
TI  - An ear-worn sensor for the detection of gait impairment after abdominal surgery.
AB  - Surgery to the trunk often results in a change of gait, most pronounced during
      walking. This change is usually transient, often as a result of wound pain, and
      returns to normal as the patient recovers. Quantifying and monitoring gait
      impairment therefore represents a novel means of functional postoperative home
      recovery follow-up. Until now, this type of assessment could only be made in a
      gait lab, which is both expensive and labor intensive to administer on a large
      scale. The objective of this work is to validate the use of an ear-worn activity
      recognition (e-AR) sensor for quantification of gait impairment after abdominal
      wall and perianal surgery. The e-AR sensor was used on 2 comparative simulated
      data sets (N = 32) of truncal impairment to observe walking patterns. The sensor
      was also used to observe the walking patterns of preoperative and postoperative
      surgical patients who had undergone abdominal wall (n = 5) and perianal surgery
      (n = 5). Methods for multiresolution feature extraction, selection, and
      classification are investigated using the raw ear-sensor data. Results show that
      the method demonstrates a good separation between impaired and nonimpaired
      classes for both simulated and real patient data sets. This indicates that the e
      AR sensor may be used as a tool for the pervasive assessment of postoperative
      gait impairment, as part of functional recovery monitoring, in patients at their
      own homes.

PMID- 22641466
TI  - Facile synthesis of budding yeast a-factor and its use to synchronize cells of
      alpha mating type.
AB  - The ease with which populations of the budding yeast Saccharomyces cerevisiae can
      be synchronized using the mating pheromone alpha-factor has been invaluable for
      studies of the cell cycle. The alpha-factor response pathway has also remained an
      important model to study the molecular mechanism of G-protein coupled receptor
      signalling. alpha-Factor is a 13 amino acids long peptide that is readily
      available by automated peptide synthesis. However, only cells of the a mating
      type respond to alpha-factor. Cells of the opposite alpha mating type respond to
      a-factor, a farnesylated and C-terminally methylated 12 amino acids peptide.
      Because of its more difficult chemical synthesis, a-factor is not readily
      available and consequently the a-factor response is less well understood. Here we
      describe an improved strategy for producing a-factor, based on solid-phase
      peptide synthesis, followed by two simple steps in solution that show favourable
      characteristics and good yield. We demonstrate the successful use of the
      resulting a-factor to synchronize cell cycle progression of alpha cells. Notably,
      the a-factor concentrations required for cell synchronization are an order of
      magnitude lower than typically used alpha-factor concentrations. Despite a
      similar cell cycle response, shmoo formation was less pronounced compared to
      alpha-factor-treated a cells. Our protocol makes a-factor widely accessible,
      extending the ease of cell cycle synchronization to budding yeast cells of both
      mating types and facilitating the study of a-factor signalling.

PMID- 22641467
TI  - Management of an infected aortic graft with endovascular stent grafting.
AB  - Aortic graft infection, one of the most common fatal complications of
      aortovascular surgery, is managed mainly by the removal of infected graft
      material and re-establishment of vascular continuity using an extra-anatomical
      bypass or in situ graft replacement. Despite significant progress in
      perioperative, surgical, and medical treatments, the mortality and morbidity for
      this condition remain high. Here, we report the use of endograft implantation and
      prolonged intravenous antibiotics to successfully treat a life-threatening Dacron
      aortic tube graft infection and anastomotic leak. Although the gold standard is
      surgical removal of infected material and repair with a homograft, in certain
      extremely high-risk patients such as ours, an alternate strategy may be warranted
      when the risks associated with surgery are prohibitive. Endovascular repair of a
      surgical Dacron graft leak may provide a novel temporizing measure in the acute
      setting, allowing for delayed semi-urgent surgical intervention, or it may
      provide a definitive treatment, as in our case. At the four-year follow-up, our
      patient was well with a good quality of life and with no clinical, radiological,
      or biochemical evidence of infection.

PMID- 22641468
TI  - Early landmark analysis of imatinib treatment in CML chronic phase: less than 10%
      BCR-ABL by FISH at 3 months associated with improved long-term clinical outcome.
AB  - Imatinib has dramatically improved the clinical outcome in chronic myeloid
      leukemia, chronic phase (CMLcp), but a risk of resistance and serious disease
      progression still prevails. We have studied 45 newly diagnosed CMLcp patients
      initiated on imatinib, assessing treatment responses by interphase extral signal
      (ES)-fluorescence in situ hybridization (FISH), quantitative real-time (q-RT)
      polymerase chain reaction (PCR), and chromosome banding analysis. In a landmark
      analysis, an early favorable response, defined as less than 10% BCR-ABL-positive
      cells by FISH after 3 months of treatment, was identified as a predictive marker
      of an improved long-term clinical outcome. Of evaluable patients, 51% achieved
      this response. A large majority, 95% of such responders reached complete
      cytogenetic responses (CCyR) within 12 months and 100% event-free survival (EFS)
      at 48 months, when compared with 67 and 65%, respectively, of patients with
      higher breakpoint cluster region - Abelson (BCR-ABL) positivity at 3 months (P =
      0.04; P = 0.006). No similar, significant correlations were noted between early
      disease assessments with PCR of BCR-ABL mRNA transcripts or of cytogenetics
      versus a 12-month CCyR or long-term EFS. Our data, based on a limited patient
      cohort, indicate that (i) FISH can effectively be used in the early assessment of
      remaining Ph-positive cells to identify patients at risk for a long-term
      nonoptimal response to imatinib and that (ii) FISH may be more useful than PCR
      for this purpose.

PMID- 22641469
TI  - Upregulation of Shh and Ptc1 in hyperoxia-induced acute lung injury in neonatal
      rats.
AB  - The aim of the present study was to observe the expression of sonic hedgehog
      (Shh) and Ptc signaling molecules in the lungs of newborn rats exposed to
      prolonged hyperoxia, and to explore the role of the SHH signaling pathway in
      hyperoxia-induced lung injury. Newborn Sprague-Dawley rat pups were placed in
      chambers containing room air or oxygen above 95% for 14 days following birth. The
      rats were sacrificed after 3, 7 or 14 days and their lungs were removed. Sections
      were fixed and subjected to hematoxylin and eosin (H&E) staining. Shh and Ptc1
      were quantitated by immunohistochemistry. The total RNA and protein were also
      extracted from lung tissue; real-time PCR (RT-PCR) and western blot analysis were
      utilized to assess the mRNA and protein expression of Shh and Ptc1. H&E staining
      demonstrated significant histomorphological changes in the hyperoxia-exposed
      lungs at 3, 7 and 14 days of age. The results of the immunohistochemistry, RT-PCR
      and western blot analysis demonstrated that the expression of Shh was
      significantly higher in the hyperoxia-exposed lungs at 3, 7 and 14 days, while
      Ptc1 was significantly elevated at 7 and 14 days. Exposure of the neonatal rat
      lung to prolonged hyperoxia resulted in acute lung injury and histomorphological
      changes. Shh and Ptc1 were upregulated in a time-dependent manner in the course
      of hyperoxia-induced lung injury. The SHH signal pathway may be involved in the
      pathogenesis of hyperoxia-induced lung injury. This is the first evidence that in
      vivo hyperoxia induces activation of the SHH signal transduction pathway in
      newborn lung.

PMID- 22641470
TI  - A technique for capturing broad subtypes and circulating recombinant forms of HIV
      1 based on anionic polymer-coated magnetic beads.
AB  - Magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic
      anhydrate) [poly(MVE-MA)], were used in a method to capture human
      immunodeficiency virus type-1 (HIV-1). The beads were incubated with either HIV-1
      infected cell culture medium or plasma from HIV-1 infected individuals and
      separated from the supernatant by applying a magnetic field. After thorough
      washing, adsorption of HIV-1 by the beads was confirmed by reverse transcription
      (RT)-polymerase chain reaction (PCR), real-time PCR, enzyme-linked immunosorbent
      assay and western blotting. The results confirmed the presence of envelope,
      polymerase, Nef and the viral genome of HIV-1. Furthermore, various subtypes and
      circulating recombinant forms (CRFs) of HIV-1 including subtype B, C and CRF01_AE
      and the immature form of subtype B HIV-1 could be captured. Preincubation with
      neutralizing antibody against HIV-1 envelope gp41 decreased the capture
      efficiently, suggesting that poly(MVE-MA) binds HIV-1 via gp41. We believe that
      this capture procedure will be a valuable tool for detecting various types of HIV
      1 in both clinical and experimental samples.

PMID- 22641471
TI  - Rational design and nanofabrication of gecko-inspired fibrillar adhesives.
AB  - Gecko feet integrate many intriguing functions such as strong adhesion, easy
      detachment, and self-cleaning. Mimicking gecko toe pad structure leads to the
      development of new types of fibrillar adhesives useful for various applications.
      In this Concept article, in addition to the design of adhesive mimics by
      replicating gecko geometric features, we show a new trend of rational design by
      adding other physical, chemical, and biological principles on to the geometric
      merits, for enhancing robustness, responsive control, and durability. Current
      challenges and future directions are highlighted in the design and
      nanofabrication of biomimetic fibrillar adhesives.

PMID- 22641472
TI  - 3,3'-Bicarbazole-based host materials for high-efficiency blue phosphorescent
      OLEDs with extremely low driving voltage.
AB  - Four types of functionalized 3,3'-bicarbazole derivatives are prepared and
      investigated as a host material for blue phosphorescent OLEDs. By using a 3,3'
      bicarbazole derivative/FIrpic film as an emissive layer, high power efficiency of
      46 lm W(-1) (45 cd A(-1), EQE 20%) with an extremely low driving voltage at 3.1 V
      is obtained at 100 cd m(-2).

PMID- 22641473
TI  - State-of-the-art in downstream processing of monoclonal antibodies: process
      trends in design and validation.
AB  - Monoclonal antibodies (mAbs) are the most important family of biopharmaceutical
      compounds in terms of market share. At present, 30 mAbs have been approved and
      are now commercialized for therapeutic purposes. mAbs are typically produced by
      mammalian cell culture in bioreactors that range in scale of 1-20 m(3) .
      Regardless of scale, from laboratory to commercial settings, the recovery and
      purification of mAbs present important challenges. Depending on the scale, the
      particular product, and the type of production process (bioreactor operation,
      process time, complexity of the culture media, cell density, etc.), many possible
      downstream configurations are possible and have been used. In this contribution,
      we review each type of unit operation that forms a downstream train for mAb
      production. We provide information regarding typical operation settings and
      critical variables for centrifugation, ultrafiltration, affinity chromatography,
      ion exchange chromatography, and viral removal operations. In addition, we
      discuss some important considerations required for the formulation of drugs based
      on mAbs.

PMID- 22641474
TI  - Impact of sirolimus and tacrolimus on mortality and graft loss in liver
      transplant recipients with or without hepatitis C virus: an analysis of the
      Scientific Registry of Transplant Recipients Database.
AB  - By analyzing 26,414 patients [12,589 with hepatitis C virus (HCV)] in the
      Scientific Registry of Transplant Recipients Database, we sought to determine
      comparative risk factors (including primary immunosuppression) predictive of
      death and graft loss among patients with HCV and patients without HCV.
      Immunosuppression was examined at the baseline and as a time-dependent variable,
      and the results were stratified by the transplant center and were adjusted for
      variables well known to affect patient and graft survival. A multivariate
      analysis of patient mortality demonstrated that recipient age, donor age,
      hepatocellular carcinoma, diabetes, and creatinine were significantly associated
      with increased 3-year mortality for both groups. Tacrolimus-based
      immunosuppression was associated with superior survival in both groups. In
      contrast, the use of sirolimus was strongly associated with increased mortality
      in the HCV group, and cyclosporine was associated with increased mortality in the
      non-HCV group. Adjusting for known and unknown factors predictive of
      posttransplant outcomes, a propensity analysis confirmed the association of
      sirolimus use with an increased risk of death in HCV patients as well as the
      association of tacrolimus use with a decreased risk of death in all patients. In
      conclusion, this study suggests a novel association between sirolimus use and an
      increased risk of death and graft loss after liver transplantation in HCV
      patients that is not seen in patients without HCV. This study confirms the
      association of tacrolimus with superior outcomes. Sirolimus should be used
      sparingly in recipients with HCV infections.

PMID- 22641476
TI  - Construction of an insertion marker collection of Sz. japonicus (IMACS) for
      genetic mapping and a fosmid library covering its genome.
AB  - Measuring relative genetic distances is one of the best ways to locate genetic
      loci. Here we report the construction of a strains set for genetic mapping in
      Schizosaccharomyces japonicus, which belongs to the genus Schizosaccharomyces
      together with the well-studied fission yeast Sz. pombe. We constructed 29 strains
      that bear a positive-negative selection marker at different loci. The marker was
      inserted every 500 kb in the genome of Sz. japonicus. Each marker thus becomes a
      'scale mark' of a chromosome that behaves like a yardstick. By determining the
      genetic distances from the inserted markers, the relative location of a genomic
      mutation can be determined. We also constructed a fosmid library that covers an
      entire genome of Sz. japonicus. These tools together would facilitate
      identification and cloning of the gene.

PMID- 22641475
TI  - Balancing target flexibility and target denaturation in computational fragment
      based inhibitor discovery.
AB  - Accounting for target flexibility and selecting "hot spots" most likely to be
      able to bind an inhibitor continue to be challenges in the field of structure
      based drug design, especially in the case of protein-protein interactions.
      Computational fragment-based approaches using molecular dynamics (MD) simulations
      are a promising emerging technology having the potential to address both of these
      challenges. However, the optimal MD conditions permitting sufficient target
      flexibility while also avoiding fragment-induced target denaturation remain
      ambiguous. Using one such technology (Site Identification by Ligand Competitive
      Saturation, SILCS), conditions were identified to either prevent denaturation or
      identify and exclude trajectories in which subtle but important denaturation was
      occurring. The target system used was the well-characterized protein cytokine IL
      2, which is involved in a protein-protein interface and, in its unliganded
      crystallographic form, lacks surface pockets that can serve as small-molecule
      binding sites. Nonetheless, small-molecule inhibitors have previously been
      discovered that bind to two "cryptic" binding sites that emerge only in the
      presence of ligand binding, highlighting the important role of IL-2 flexibility.
      Using the above conditions, SILCS with hydrophobic fragments was able to identify
      both sites based on favorable fragment binding while avoiding IL-2 denaturation.
      An important additional finding was that acetonitrile, a water-miscible fragment,
      fails to identify either site yet can induce target denaturation, highlighting
      the importance of fragment choice.

PMID- 22641477
TI  - Self-assembly of polyoxotungstate with tetrarhodium-oxo core: synthesis,
      structure and 183W NMR studies.
AB  - A sandwich-type rhodium polyoxotungstate with unprecedented tetrarhodium-oxo core
      Na(12)[(Rh(4)(MU(3)-O)(2)(H(2)O)(2))(H(2)W(9)O(33))(2)].38H(2)O (1) was obtained
      by hydrothermal reaction of rhodium(II) acetate and sodium tungstate; crystal
      structure was determined by X-ray diffractometry and was confirmed by (183)W NMR
      data; 1 is active in electrocatalytic water oxidation.

PMID- 22641478
TI  - Oral administration of Enterococcus faecalis FK-23 suppresses Th17 cell
      development and attenuates allergic airway responses in mice.
AB  - Evidence is increasing that oral administration of probiotics can attenuate
      asthmatic responses both in murine models and clinical trials. T-helper 17 (Th17)
      cells, a subset of CD4+ T cells have been implicated as having an important role
      in the development of several allergic disorders, but the relationship between
      oral administration of probiotics and Th17 development has not been well studied.
      BALB/c mice were given lysed Enterococcus faecalis FK-23 (LFK) orally for 28
      days. After sensitization by subcutaneous injection of ovalbumin (OVA) on Days 14
      and 21 and 1% OVA inhalation on Days 25, 26 and 27, they were challenged with a
      5% OVA aerosol on Day 28. Twenty-four hours later, airway resistance and
      accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF) and
      lung tissues were determined. Iotanterleukin (IL)-17-expressing CD4+ lymphocytes
      isolated from lung, spleen and lamina propria of the intestine were detected by
      flow cytometry. The expression of IL-6 and TGF-beta mRNA was assessed by real
      time PCR. Increases in airway hyperresponsiveness, and numbers of total
      leukocytes and mast cells in BALF induced by OVA challenge were significantly
      suppressed by oral administration of LFK. The increased percentage of IL-17
      expressing CD4+ cells from lung, spleen and intestine in OVA-challenged mice was
      reduced following LFK treatment. We conclude that the oral administration of LFK
      suppresses the asthmatic response and that this is associated with attenuation of
      Th17 cell development.

PMID- 22641479
TI  - A functional promoter polymorphism of the delta-globin gene is a specific marker
      of the Arab-Indian haplotype.

PMID- 22641481
TI  - Dimension-controlled synthesis of CdS nanocrystals: from 0D quantum dots to 2D
      nanoplates.
AB  - The dimension-controlled synthesis of CdS nanocrystals in the strong quantum
      confinement regime is reported. Zero-, one-, and two-dimensional CdS nanocrystals
      are selectively synthesized via low-temperature reactions using alkylamines as
      surface-capping ligands. The shape of the nanocrystals is controlled
      systematically by using different amines and reaction conditions. The 2D
      nanoplates have a uniform thickness as low as 1.2 nm. Furthermore, their optical
      absorption and emission spectra show very narrow peaks indicating extremely
      uniform thickness. It is demonstrated that 2D nanoplates are generated by 2D
      assembly of CdS magic-sized clusters formed at the nucleation stage, and
      subsequent attachment of the clusters. The stability of magic-sized clusters in
      amine solvent strongly influences the final shapes of the nanocrystals. The
      thickness of the nanoplates increases in a stepwise manner while retaining their
      uniformity, similar to the growth behavior of inorganic clusters. The 2D CdS
      nanoplates are a new type of quantum well with novel nanoscale properties in the
      strong quantum confinement regime.

PMID- 22641480
TI  - Ursolic acid inhibits growth and induces apoptosis in gemcitabine-resistant human
      pancreatic cancer via the JNK and PI3K/Akt/NF-kappaB pathways.
AB  - Pancreatic cancer is one of the most deadly carcinomas worldwide. Although
      gemcitabine as the standard chemotherapy agent has been proven to be effective,
      the response rate remains at 5.4% and the 5-year survival rate is extremely poor.
      Ursolic acid (UA) is a small molecule compound extracted from Chinese herbs as
      well as edible vegetables and a well-known anti-inflammatory and
      immunosuppressive agent. Here, we show that UA has potential to be developed into
      an anti-neoplastic agent against gemcitabine-resistant pancreatic cancer and to
      explore its molecular mechanism of action. In vitro, we used three different
      malignancy grades of pancreatic resistant cancer cell lines including MIA PaCa-2,
      PANC-1 and Capan-1 to assess the antitumor effect of UA. We found that UA
      inhibited growth and induced apoptosis in a dose-dependent manner in all of the
      three pancreatic cancer cell lines. Both extrinsic and intrinsic pathways were
      found to be involved in apoptotic cascade. The potential signaling pathways are
      concerned with inactivation of the PI3K/Akt/NF-kappaB pathway and activation of
      the c-Jun-terminal kinase (JNK) pathway. The JNK inhibitor SP600125 partly
      abrogated the caspase-9 activation caused by UA. The Akt inhibitor LY294002 did
      not mimic the effect of UA on caspase-8 and -9, but inhibited the viability of
      MIA PaCa-2 cells to some extent. Equally, UA also overcame the chemoresistance in
      the chemoresistant endometrial and ovarian carcinoma cell lines (HEC-1A and OVCAR
      3). Moreover, UA caused cytotoxicity to a nude mouse xenograft model in vivo.
      Therefore, our present data suggest that UA can act as a novel and potent
      therapeutic agent in gemcitabine-resistant pancreatic cancer and even as a
      promising candidate in other chemoresistant cancers.

PMID- 22641482
TI  - Isothermally reversible fluorescence switching of a mechanochromic perylene
      bisimide dye.
AB  - Isothermally rewritable fluorescence mechanochromism has been realized for a
      perylene bisimide dye with bulky and flexible substituents. Fluorescent patterns
      drawn by mechanical stimuli can be erased by thermal stimuli, treatment with
      solvent vapors, or spontaneous structural transition from orange-fluorescent to
      green-fluorescent states. The isothermal fluorescence switching of solid dye
      films is applicable to displays and sensory materials.

PMID- 22641483
TI  - Development toward rapid and efficient screening for high performance hydrolysate
      lots in a recombinant monoclonal antibody manufacturing process.
AB  - Plant-derived hydrolysates are widely used in mammalian cell culture media to
      increase yields of recombinant proteins and monoclonal antibodies (mAbs).
      However, these chemically varied and undefined raw materials can have negative
      impact on yield and/or product quality in large-scale cell culture processes.
      Traditional methods that rely on fractionation of hydrolysates yielded little
      success in improving hydrolysate quality. We took a holistic approach to develop
      an efficient and reliable method to screen intact soy hydrolysate lots for
      commercial recombinant mAb manufacturing. Combined high-resolution (1) H nuclear
      magnetic resonance (NMR) spectroscopy and partial least squares (PLS) analysis
      led to a prediction model between product titer and NMR fingerprinting of soy
      hydrolysate with cross-validated correlation coefficient R(2) of 0.87 and root
      mean-squared-error of cross-validation RMSECV% of 11.2%. This approach screens
      for high performance hydrolysate lots, therefore ensuring process consistency and
      product quality in the mAb manufacturing process. Furthermore, PLS analysis was
      successful in discerning multiple markers (DL-lactate, soy saccharides, citrate
      and succinate) among hydrolysate components that positively and negatively
      correlate with titer. Interestingly, these markers correlate to the metabolic
      characteristics of some strains of taxonomically diverse lactic acid bacteria
      (LAB). Thus our findings indicate that LAB strains may exist during hydrolysate
      manufacturing steps and their biochemical activities may attribute to the titer
      enhancement effect of soy hydrolysates.

PMID- 22641484
TI  - The use of rituximab therapy in patients with acquired factor V inhibitors.

PMID- 22641485
TI  - What is the state of the stone analysis techniques in urolithiasis?
AB  - PURPOSE: To compare and evaluate the mostly used methods of urinary stone
      analysis. MATERIALS AND METHODS: We searched PubMed and Google Scholar for
      "urolithiasis, nephrolithiasis, renal stone, and kidney stone" combined with
      "stone analysis, spectroscopy, X-ray diffraction, chemical analysis, mass
      spectrometry, and laser-induced breakdown spectroscopy, review article, and
      quality control assessment". RESULTS: We identified 24 articles about reviews of
      the principles of stone analysis techniques and their quality control trials.
      Seven articles were not in English language; hence, were omitted from this
      review. The remaining 17 articles and their related references were studied
      thoroughly. There are various chemical and physical techniques available for
      urinary stone analysis. The correct stone analysis has to identify not only all
      stone components, but also the molecular structure and crystalline forms of them
      with the exact quantitative determination of each component. CONCLUSION: The
      knowledge of urinary stone composition is important for understanding
      pathophysiology, choice of treatment modality, and prevention of recurrences of
      urolithiasis, but up to now, a standard method has not been defined. Although
      there are many techniques available for identifying the urinary stone composition
      and structure, no single method can provide all the requiring information.
      Therefore, a combination of structural and morphological tests is needed for this
      purpose.

PMID- 22641486
TI  - When is an ectopically placed ureteral stent acceptable?

PMID- 22641487
TI  - Absent inferior vena cava with resulting bladder varices: a rare cause of frank
      hematuria.

PMID- 22641488
TI  - Revisiting the predictive factors for intra-operative complications of rigid
      ureteroscopy: a 15-year experience.
AB  - PURPOSE: To revise the predictive factors for intra-operative complications of
      rigid ureteroscopy in the treatment of ureteral calculi. MATERIALS AND METHODS:
      During a 15-year period (1993 to 2008), a total of 1496 consecutive patients who
      had undergone 1660 ureteroscopy procedures were retrospectively reviewed. After
      exclusion of the cases for diagnostic purposes, diseases other than ureteral
      calculi, and repeated ureteroscopy procedures, 1189 patients were left as the
      study population. Those patients were then divided into two groups based on the
      presence of the complications: complication-positive (group 1, n = 57) and
      complication-negative (group 2, n = 1132). Both groups were statistically
      compared regarding patients' age and gender, stone surface area, lateralization
      and localization of the stone, impaction of the stone, type of the ureteroscope,
      necessity of ureteral orifice dilation, and use of a catheter during and after
      the procedure. Furthermore, the effect of leaving the fragmented stones in situ
      small enough to pass spontaneously (break'n'leave) on occurring of the
      complications has been investigated. RESULTS: The complication rate was recorded
      as 4.7%. Success rate after a single intervention was 86.3%, whereas increased to
      94.1% after ancillary procedures. Stone surface area, lateralization, and type of
      lithotripter used were comparable between the groups, but impacted stones and the
      stones located at the upper ureters were associated with significantly increased
      complication rates. Furthermore, significantly less complication has been
      observed in cases where we performed break'n'leave. Furthermore, multivariate
      analysis revealed that stone impaction and failure to adhere to the
      "break'n'leave" principle were the independent predictors of occurring of the
      complications. CONCLUSION: Ureteroscopy is safe and effective in the treatment of
      ureteral calculi. Careful attention for the patients having a potential for
      occurrence of the complications and selection of the techniques are of importance
      for reducing untoward events.

PMID- 22641489
TI  - Pediatric percutaneous nephrolithotomy using adult sized instruments: our
      experience.
AB  - PURPOSE: To evaluate the safety and efficacy of pediatric percutaneous
      nephrolithotomy (PCNL) using adult sized instruments in the management of
      pediatric urolithiasis. MATERIALS AND METHODS: We retrospectively reviewed the
      medical records of 38 children younger than 15 years who had undergone 45 PCNLs
      with adult sized instruments in our center between August 2007 and February 2010.
      RESULTS: There were 26 boys and 12 girls, with a mean age of 8.4 +/- 4.24 years
      (range, 12 months to 13 years). Twelve patients had complete staghorn stone. Mean
      stone burden was 2.93 +/- 0.89 cm. The tract was dilated between 26 and 30F.
      Standard PCNL was performed in 8 patients and tubeless PCNL in the next 37
      subjects. Simultaneous transurethral lithotripsy was done in 9 patients. Stone
      clearance rate was 67%. Mean pre and postoperative hemoglobin levels were 12.67
      +/- 1.7 and 11.39 +/- 1.6 g/dL, respectively. Mean hospitalization was 3.5 +/-
      1.1 days. Eight subjects had postoperative fever beyond day 1. Blood transfusion
      was required in only one patient. In one patient (3 years old) with a staghorn
      stone, hyponatremia and seizure occurred, which were treated conservatively
      without any adverse sequela. There was a significant difference in hospital stay
      between tubeless and standard PCNL groups (P < .02). CONCLUSION: We concluded
      that PCNL using adult sized instruments was relatively safe in children, with a
      clearance rate of 67%. We suggest prospective randomized studies to compare mini
      perc and adult sized instruments use in pediatric PCNL.

PMID- 22641490
TI  - Effect of hydroalcoholic extract of Hypericum perforatum L. leaves on ethylene
      glycol-induced kidney calculi in rats.
AB  - PURPOSE: To investigate the effects of the hydroalcoholic extract of Hypericum
      perforatum (H. perforatum) leaves on the kidney calculi in rats. MATERIALS AND
      METHODS: Fifty-two Wistar male rats were randomly divided into 4 groups: Groups
      2, 3, and 4 received ethylene glycol (EG) 1% + ammonium chloride (0.5%)-added
      drinking water as a stone inducer. The H. Perforatum solution was fed at the same
      time of EG application and was repeated once for two days until the end of the
      experimental period. Group 1 (control; n = 10) was provided free access to food
      and normal drinking water. Group 2 (EG; n = 12) received EG-ammonium chloride
      added drinking water and was fed with normal chow. Groups 3 and 4 (n = 15), as EG
      treatment groups, received H. Perforatum in low (300 mg/kg) and high (500 mg/kg)
      doses, respectively. After 28 days, the kidneys were removed and prepared for
      histologic evaluation of calcium oxalate deposits. RESULTS: Urine level of free
      calcium in groups EG and EG + H. perforatum (300 mg/kg) and phosphorous in EG +
      H. perforatum (500 mg/kg) significantly decreased compared to controls (P < .01;
      P < .05; and P < .05, respectively). Treatment of the rats with high dose of H.
      Perforatum (500 mg/kg) markedly reduced decrementing effect of EG on serum level
      of free calcium (P < .05). Histological experiments showed that chronic feeding
      of H. perforatum (300 and 500 mg/kg, orally) could significantly reduce the size
      and number of calcium oxalate deposits in EG group. CONCLUSION: Chronic treatment
      of rats with hydroalcoholic extract of H. perforatum reduced the size and number
      of calcium oxalate deposits in EG-induced calculi.

PMID- 22641491
TI  - Clipless laparoscopic retroperitoneal lymph node dissection using bipolar
      electrocoagulation for sealing lymphatic vessels: initial series.
AB  - PURPOSE: To evaluate the outcome of laparoscopic retroperitoneal lymph node
      dissection (LRPLND) using bipolar electrocoagulation instead of clipping the
      lymphatic vessels. MATERIALS AND METHODS: Between August 2002 and April 2008, a
      total of 13 patients underwent transperitoneal LPRLND for nonseminomatous germ
      cell tumor of the testis. In this experience, in contrast to other techniques, we
      did not use clips for ligation of the lymphatic vessels; instead, we used bipolar
      cautery for coagulation of the lymphatic vessels. We followed up the patients for
      lymphocele formation or lymphatic leakage using abdominal computed tomography
      scan. RESULTS: Mean age of the patients was 24.2 years (range, 19 to 39 years).
      Six tumors were on the left side and 7 on the right. Pathological stage was I in
      12 patients and IIA in one. The mean follow-up period was 29.9 months (range, 3
      to 70 months). No re-operation was required. There was no prolonged lymphatic
      leakage or lymphocele formation during the follow-up period. CONCLUSION: Our
      study demonstrates that using bipolar electrocoagulation instead of clips, for
      sealing of the lymphatic vessels during LRPLND, does not hamper the outcome of
      the procedure. This should be further evaluated in randomized clinical trials
      with more subjects.

PMID- 22641492
TI  - Inter/intra-observer reproducibility of Gleason scoring in prostate
      adenocarcinoma in Iranian pathologists.
AB  - PURPOSE: To measure the level of inter/intra-observer reproducibility among
      pathologists as far as Gleason scoring of adenocarcinoma of the prostate is
      concerned. MATERIALS AND METHODS: A total of 101 prostate biopsy slides,
      diagnosed with adenocarcinoma of the prostate by five pathologists from different
      education centers, were exposed to Gleason scoring. Two months later, the slides
      were re-examined by three of the same pathologists. Thereafter, the kappa was
      calculated for the data provided in the first and second reports of each
      pathologist and compared between pathologists. RESULTS: Inter-observer
      reproducibility was inappropriate, but intra-observer diagnostic reproducibility
      was almost perfect with a corresponding percentage of agreement of 85.2%.
      CONCLUSION: The inter-observer reproducibility was poor.

PMID- 22641493
TI  - Is it effective to perform two more prostate biopsies according to prostate
      specific antigen level and prostate volume in detecting prostate cancer?
      Prospective study of 10-core and 12-core prostate biopsy.
AB  - PURPOSE: To evaluate the effectiveness of 2 more core prostate biopsy protocol in
      detecting the prostate cancer (PCa) by comparing 10-core prostate biopsy with 12
      core according to the prostate-specific antigen (PSA) level and the prostate
      volume. MATERIALS AND METHODS: A total of 474 men with elevated serum levels of
      PSA between 2.5 and 20.0 ng/mL, regardless of abnormal finding on digital rectal
      examination and transrectal ultrasonography, received transrectal ultrasound
      guided prostate biopsies. The patients were prospectively randomized to undergo
      10-core (group 1, n = 351) or 12-core (group 2, n = 123) biopsy. The PCa
      detection rates were assessed and compared according to the serum level of PSA
      and prostate volume. RESULTS: Of 474 men, 128 (27.0%) were diagnosed with PCa.
      The PCa detection rates of 10-core and 12-core biopsies were 26.4% and 28.4%,
      respectively (P = .378). There was no difference in cancer detection rates
      according to PSA level in both groups. Comparing the cancer detection rates
      according to the prostate volume (< 40 mL and >= 40 mL), the patients with
      prostate volume >= 40 mL showed higher cancer detection rates in 12-core biopsy
      group (26.9%) compared with 10-core biopsy group (16.4%) (P < .05). CONCLUSION:
      The overall cancer detection rates showed no differences in both groups. But the
      12-core biopsy was a more efficient method in men with a prostate volume of >= 40
      mL, compared to the 10-core biopsy.

PMID- 22641494
TI  - Sexual function of primiparous women after elective cesarean section and normal
      vaginal delivery.
AB  - PURPOSE: To compare sexual function between two groups of women who had normal
      vaginal delivery (NVD) and planned cesarean section (PCS). MATERIALS AND METHODS:
      In this cross-sectional study, two groups of healthy women, with antenatally
      normal singleton pregnancies at term, who underwent NVD (n = 114) or PCS without
      labor (n = 99), have been retrospectively studied. Sexual function of
      participants was assessed using physician-administered Female Sexual Function
      Index (FSFI) questionnaire before pregnancy and 6 and 24 months after delivery.
      Primary outcome measures were questions 3 to 6 and 14 to 16 from FSFI
      questionnaire. Secondary outcome measures included the remaining items. RESULTS:
      There were no significant differences regarding six domains of sexual function,
      including desire (P = .55), arousal (P = .39), lubrication (P = .45), orgasm (P =
      .36), pain (P = .74), and satisfaction (P = .39) between the two groups. Eighty
      percent of women who had undergone vaginal delivery complained from hypotonic
      pelvic floor muscles. CONCLUSION: We believe that PCS is not preferred to NVD in
      regard to preserving normal sexual functioning.

PMID- 22641495
TI  - Effects of varicocele repair on spontaneous first trimester miscarriage: a
      randomized clinical trial.
AB  - PURPOSE: To evaluate the effects of varicocelectomy on semen parameters,
      pregnancy rates, and live birth in couples with first term recurrent miscarriage.
      MATERIALS AND METHODS: One hundred and thirty-six women with recurrent
      miscarriage were recruited into this study. All of the husbands had normal semen
      parameters according to World Health Organization criteria and clinical
      varicocele. In order to evaluate the causes of recurrent pregnancy loss, we
      looked for chromosomal abnormalities and endocrine, chronic inflammatory, and
      infectious diseases. Both groups were well matched according to male/female age,
      varicocele grade, and smoking history. These couples were assigned randomly into
      two groups: group one (n = 68), in which male partners underwent varicocele
      repair, and group two (n = 68), which underwent expectant therapy. All of the
      couples were followed up monthly up to 12 months. All of the women who conceived
      were followed up until delivery. In each 3-month follow-up visits, two semen
      analyses were performed. RESULTS: Mean sperm concentration, sperm progressive
      motility, and sperm with normal morphology improved significantly after elapsing
      6 months from varicocelectomy by 75.0%, 15.9%, and 14.3%, respectively, versus
      the expectant group (P < .01). The overall pregnancy rate was 44.1% and 19.1%
      within a 12-month period in groups 1 and 2, respectively (P = .003). Of women who
      conceived in groups 1 and 2, 13.3% and 69.2% developed miscarriage (P = .001).
      Sperm density/mL (r = 0.072; P = .001), time elapsed from varicocelectomy (r =
      0.068; P = .001), and female age (r = -0.062; P = .002) were three most
      significantly related independent factors to pregnancy rate by multiple
      regression analysis. CONCLUSION: Varicocelectomy improves semen quality,
      increases pregnancy rate, and decreases miscarriage rate significantly. Further
      controlled studies to confirm our results seem warranted.

PMID- 22641497
TI  - Needle manipulation for removing inaccessible stones in parallel calices during
      percutaneous nephrolithotomy.

PMID- 22641496
TI  - Tubularized incised plate urethroplasty using buccal mucosa graft for repair of
      penile hypospadias.
AB  - PURPOSE: To describe the results of penile hypospadias repair using the Snodgrass
      method with buccal mucosa graft (BMG), supported by double dartos flap as a
      second layer. MATERIALS AND METHODS: In a prospective cohort study, 21
      consecutive patients underwent hypospadias repair using the Snodgrass method and
      BMG as the urethral plate, with the addition of double dartos flap for covering
      the neourethra. Patients were followed up, and outcomes and complications were
      recorded. RESULTS: The mean age of the patients was 6.57 +/- 3.69 years (range, 2
      to 15 years) and the mean follow-up period was 8.42 +/- 2.19 months (range, 6 to
      12 months). The following minor complications, not requiring additional
      intervention, were recorded: 2 subjects developed slight chordee < 30 degrees; 2
      developed wound infection; and 1 had meatal stenosis postoperatively. Only one
      patient required additional surgical intervention resulting in a success rate of
      95%. No urethrocutaneous fistula occurred in our subjects. CONCLUSION: Fortifying
      a combination of BMG and Snodgrass method with double dartos flap decreases the
      rate of complication in hypospadias repair significantly.

PMID- 22641498
TI  - Penile Mondor's disease: long-term functional follow-up.

PMID- 22641499
TI  - Left retrocaval ureter associated with urothelial malignancy: presentation of a
      rare case.

PMID- 22641500
TI  - Urinary bladder metastasis originating from lung adenocarcinoma: a case
      definitively diagnosed by immunohistochemistry.

PMID- 22641501
TI  - Urachal adenocarcinoma: big dimensions without involvement of the bladder wall.

PMID- 22641502
TI  - UV radiation-induced skin aging in hairless mice is effectively prevented by oral
      intake of sea buckthorn (Hippophae rhamnoides L.) fruit blend for 6 weeks through
      MMP suppression and increase of SOD activity.
AB  - Oxidative stress and oxidative photodamage induced by UV radiation can cause
      serious skin damage that is characterized by wrinkling, roughness, laxity and
      pigmentation. The effects of a sea buckthorn (Hippophae rhamnoides L.) fruit
      blend (SFB) containing sea buckthorn fruit extract, blueberry extract and
      collagen on UV-induced skin aging were examined by treating hairless mice for 6
      weeks with UV irradiation and SFB administered orally. The effects of SFB were
      measured in the skin of these mice by phenotypical and histological analysis and
      western blotting. According to wrinkle formation analysis, the oral intake of SFB
      induced a decrease in wrinkle formation in the damaged skin of UV-irradiated
      mice. The thickness of the epidermis and dermis in the vitamin extracts (Vit)-
      and SFB-treated group was lower than that in the vehicle-treated group, but the
      group treated with SFB50 was the most effective group. The mice treated with the
      Vit- or SFB solution maintained a normal moisture content through the inhibition
      of transdermal water loss (TEWL) and an increase in skin moisture content.
      Furthermore, the levels of matrix metalloproteinase (MMP) and collagen protein
      expression were assessed in five groups to examine the mechanisms underlying the
      effects of SFB oral intake. The application of SFB induced a decrease in MMP-1
      and -9 expression to the levels observed in the vehicle-treated group, but MMP-9
      expression showed a much larger decrease than MMP-1. Furthermore, the expression
      of collagen-1 in the skin corresponded to MMP expression except for the SFB30
      treated group, whereas the superoxide dismutase (SOD) activity was increased
      dramatically in the SFB50-treated group. These results suggest that SFB has
      potential as a protective and therapeutic drug candidate against skin aging that
      functions by regulating the moisture content, MMP expression levels and SOD
      activity.

PMID- 22641503
TI  - Quantum chemical comparison of vertical, adiabatic, and 0-0 excitation energies:
      the PYP and GFP chromophores.
AB  - A number of benchmark studies investigating the performance of quantum chemical
      methods for calculating vertical excitation energies are today available in the
      literature. However, less established is the variation between methods in their
      estimates of the differences between vertical, adiabatic, and 0-0 excitation
      energies. To this end, such excitation energies are here calculated for the
      bright S(1) states of the anionic chromophores of the photoactive yellow protein
      (PYP) and the green fluorescent protein (GFP) in the gas phase using
      configuration interaction singles, complete active space self-consistent field,
      coupled-cluster singles and doubles, and time-dependent density functional theory
      methods. Although the estimates of the excitation energies vary by more than 1 eV
      between the methods, the differences between the different types of excitation
      energies are found to be relatively method-insensitive, varying by ~0.1 eV only
      for these particular chromophores. Specifically, the adiabatic energies are
      uniformly 0.10-0.17 (PYP) and 0.06-0.17 eV (GFP) lower than the vertical
      energies, and the 0-0 energies are similarly 0.09-0.14 (PYP) and 0.07-0.17 eV
      (GFP) lower than the adiabatic energies.

PMID- 22641505
TI  - Brazil on the road to the elimination of asbestos.

PMID- 22641504
TI  - A multi-faceted analysis of RutD reveals a novel family of alpha/beta hydrolases.
AB  - The rut pathway of pyrimidine catabolism is a novel pathway that allows
      pyrimidine bases to serve as the sole nitrogen source in suboptimal temperatures.
      The rut operon in E. coli evaded detection until 2006, yet consists of seven
      proteins named RutA, RutB, etc. through RutG. The operon is comprised of a
      pyrimidine transporter and six enzymes that cleave and further process the uracil
      ring. Herein, we report the structure of RutD, a member of the alpha/beta
      hydrolase superfamily, which is proposed to enhance the rate of hydrolysis of
      aminoacrylate, a toxic side product of uracil degradation, to malonic
      semialdehyde. Although this reaction will occur spontaneously in water, the
      toxicity of aminoacrylate necessitates catalysis by RutD for efficient growth
      with uracil as a nitrogen source. RutD has a novel and conserved arrangement of
      residues corresponding to the alpha/beta hydrolase active site, where the
      nucleophile's spatial position occupied by Ser, Cys, or Asp of the canonical
      catalytic triad is replaced by histidine. We have used a combination of
      crystallographic structure determination, modeling and bioinformatics, to propose
      a novel mechanism for this enzyme. This approach also revealed that RutD
      represents a previously undescribed family within the alpha/beta hydrolases. We
      compare and contrast RutD with PcaD, which is the closest structural homolog to
      RutD. PcaD is a 3-oxoadipate-enol-lactonase with a classic arrangement of
      residues in the active site. We have modeled a substrate in the PcaD active site
      and proposed a reaction mechanism.

PMID- 22641506
TI  - [The contribution of indigenous community health workers to special healthcare
      for Brazilian indigenous peoples].
AB  - Indigenous community health workers are part of a strategy developed by Brazil in
      the last two decades to promote a special healthcare model for indigenous
      peoples. Their role is designed to deal with various aspects of the special
      health policy, including the link between the heath team and the community and
      mediation between scientific and indigenous medical knowledge. Despite a
      significant increase in the number of indigenous community health workers in
      recent years, an evaluation of their responsibilities and contributions to the
      success of special care had not been conducted previously. This article, based on
      a literature review and original research by the authors, analyzes the role of
      the indigenous community health workers vis-a-vis their training and
      participation in health teams in different contexts in Brazil. Considering the
      importance assigned to the role of indigenous community health workers, this
      analysis reveals various ambiguities and contradictions that hinder both their
      performance and their potential contribution to the special health services.

PMID- 22641507
TI  - [Socio-demographic determinants of suicide in the State of Rio de Janeiro,
      Brazil, 1998-2002].
AB  - Epidemiology has identified violence as a major worldwide public health concern.
      Suicide is classified as violence. This study analyzes the association between
      suicide and socio-demographic factors. The methodological design was ecological,
      using correlation techniques and backward multiple linear regression. Normality
      of the residuals in the final model was analyzed. Proportional mortality in
      relation to total deaths was identified as the best outcome for modeling (R(2) =
      0.41). The resulting variables were: % Pentecostal religion, % single marital
      status in the population over 10 years of age, mean years of schooling, altitude
      of the municipality, % homes without latrines, % population over 10 years of age
      working in the educational sector, and % population over 10 years with per capita
      earnings up to one minimum wage. All these variables were statistically
      significant at 5%. The results support the idea of the influence of extrinsic
      causal factors in determination of suicide.

PMID- 22641508
TI  - [Hospitalization for primary care-sensitive conditions in Campo Grande, Mato
      Grosso do Sul State, Brazil, 2000-2009].
AB  - This study analyzed the correlation between evolution in coverage of the Family
      Health Strategy (FHS) and the hospital admissions rate for primary care-sensitive
      conditions (PCSC) in Campo Grande, Mato Grosso do Sul State, Brazil, from 2000 to
      2009. This was an ecological study using data from the Hospital Information
      System (SIH), available from the Information System of the Brazilian Unified
      National Health System (DATASUS) and the Brazilian Institute of Geography and
      Statistics (IBGE). Statistical analysis used Pearson's linear correlation
      coefficient and its significance. Campo Grande showed an inverse correlation,
      following the trend for the country as a whole, with a reduction in such
      admissions. The analysis of categories of hospital admissions showed a direct
      correlation with pulmonary tuberculosis, angina pectoris, and conditions related
      to prenatal care and childbirth. The results suggest that increased coverage of
      the FHS has contributed to a reduction in hospitalization rates for PCSC.

PMID- 22641509
TI  - [Erythropoietin use by incident hemodialysis patients in the Brazilian Unified
      National Health System, 2002-2003].
AB  - This study aimed to describe the demographic and epidemiological profile of
      Brazilian patients entering hemodialysis from 2002 to 2003 and identify
      predictors of erythropoietin use. The study analyzed demographic and clinical
      characteristics and dialysis facility-related variables from 32,136 patients
      identified by deterministic-probabilistic matching in the database of
      authorizations for high-cost procedures and the Mortality Information System.
      Poisson regression was used to identify predictors of erythropoietin use. Male
      gender, age < 65 years, diabetic renal failure, arteriovenous fistula at the
      beginning of hemodialysis, and living in States of Brazil other than Mato Grosso
      were predictors of erythropoietin use. The policy of care for chronic kidney
      disease, resource allocation for States and municipalities, and anemia management
      according to the patient's drug therapy profile need to be revised in order to
      reduce observed inequities in erythropoietin use.

PMID- 22641510
TI  - Trends in hospitalizations for respiratory diseases in Salvador, Bahia State,
      Brazil, 1998-2009.
AB  - Respiratory diseases are the leading cause of hospitalizations in Brazil
      (excluding hospital admissions related to childbirth, pregnancy, and postpartum).
      To analyze the trend and seasonality of hospitalizations for respiratory diseases
      in Salvador, Bahia State, Brazil, 1998-2009, a time trend study was performed
      using simple linear regression. Hospitalization rates for all respiratory
      diseases and specifically for asthma, chronic obstructive pulmonary disease
      (COPD), and pneumonia were calculated by year and age group. Hospitalizations for
      all respiratory diseases decreased by 45.6% (beta = -2.2; p < 0.001); those due
      to asthma showed the largest decline (annual average 1.2/10,000), pneumonia
      showed the largest reduction until 2002, subsequently tending to stabilize, and
      COPD remained unchanged. The under-5-year age group showed the largest decline in
      hospitalizations for all respiratory diseases. There was no seasonality in
      hospitalizations for COPD. There was a reduction in the burden of
      hospitalizations due to respiratory diseases in Salvador, mainly due to the drop
      in asthma and pneumonia in children < 5 years. However, the city still has
      hospitalization rates for respiratory diseases that are higher than in other
      large Brazilian cities.

PMID- 22641511
TI  - [Factors associated with influenza vaccination among the elderly: a cross
      sectional study in Cambe, Parana State, Brazil].
AB  - The aim of this study was to assess influenza immunization coverage in the
      elderly and the association between vaccination and socioeconomic, demographic,
      health, and lifestyle variables, using a descriptive cross-sectional
      epidemiological approach from April 2008 to September 2009 with 990 elderly in
      Cambe, Parana State, Brazil. Vaccination coverage was 74.6%. The highest
      vaccination rate was among individuals 70 to 79 years of age [adjusted prevalence
      ratio (PR) = 1.05] and 80 or older (PR = 1.03), with hypertension, and with
      monthly income up to 3 times the minimum wage (PR = 1.10) or higher (PR = 1.17)
      compared to elderly without income. Sedentary elderly (PR = 0.96) adhered less to
      vaccination, and divorced/separated individuals (PR = 0.92) had lower adherence
      compared to the married. The results suggest the need for healthcare strategies
      considering the factors that affect voluntary vaccination in order to help
      increase the odds of success for immunization programs.

PMID- 22641512
TI  - [Poor self-rated mastication and associated factors in Brazilian adults].
AB  - This study estimated the prevalence of bad/very bad self-rated mastication and
      investigated associated factors among Brazilian adults. The sample included
      13,431 adults examined and interviewed in the SBBrazil project. Self-rated
      mastication was combined in three categories: good/ very good (the reference),
      fair, and bad/very bad. Multinomial logistic regression was performed to measure
      the association between fair and bad/very bad self-rated mastication and all
      independent variables included in the analysis, with significance set at p <
      0.05. 55.6% of participants rated their mastication as good/very good, 24.9% as
      fair, and 19.5% as bad/very bad. In the final multivariate analysis, factors
      associated with bad or fair self-rated mastication were: receiving no information
      on how to avoid oral problems; presenting fewer than 23 remaining teeth;
      requiring total or partial prosthesis; bad/very bad self-rated oral health;
      gingival pain and/or toothache in the previous year; and need of dental
      treatment. In conclusion, various factors were associated with self-rated
      mastication, especially subjective conditions, thus emphasizing its importance as
      an oral health indicator.

PMID- 22641513
TI  - Prevalence of self-reported chronic diseases in individuals over the age of 40 in
      Sao Paulo, Brazil: the PLATINO study.
AB  - Few studies have been conducted to determine the prevalence of chronic diseases
      and its impact in individuals aged 40 years or over in Brazil. The objective of
      this study is to evaluate the prevalence of some common chronic diseases in the
      Brazilian subgroup assessed by the PLATINO study using a self-reported survey. A
      total of 918 individuals (55% women) with a mean age of 54.6 +/- 10.9 years were
      evaluated. The most prevalent diseases were obesity (62.5%), hypertension (39.2%)
      and gastritis (30.9%). We conclude from this study that there is a high
      prevalence of chronic diseases in the population over 40 years of age: 88% of the
      population suffers from a minimum of one disease and 26% of the sample suffers
      from at least three diseases. We also observed that the number of comorbidities
      increases with age.

PMID- 22641514
TI  - [Effect of sampling plan on ordinal logistic models: an analysis of self-rated
      health status among Brazilian adults based on the National Household Sample
      Survey (PNAD 2008)].
AB  - Studies that draw on individual and environmental variables to explain
      differences in self-rated health status have increased gradually in Brazil, but
      are still limited in number. Due to time and cost issues, many studies use a
      complex sample design involving features (stratification, clustering, and
      different sample weights) that, when ignored, can influence odds ratios and
      standard errors in the statistical models. Using the National Household Sample
      Survey (PNAD 2008), this paper assesses the impact on these measurements when
      some or all of these features are not taken into account in fitting ordinal
      logistic models to establish associations between adults' self-rated health and
      various individual and environmental factors. According to this study, failure to
      take these three features into account simultaneously led to changes in the
      magnitude of the odds ratio between better self-rated health and most of the
      factors, besides important underestimation of standard errors.

PMID- 22641515
TI  - [Metropolitan and regional health planning: dilemmas of the Pact for Health in
      the Baixada Santista Metropolitan Area, Sao Paulo State, Brazil].
AB  - This paper focuses on the relationship between metropolitan and regional health
      planning based on the processes of regionalization and the Pact for Health in the
      Baixada Santista Metropolitan Area, Sao Paulo State, Brazil. The method used was
      a case study in two stages, namely during initial implementation of the Pact for
      Health (2007) and the Regional Administration Committees (CGR) and in 2010.
      Municipal and regional health systems managers and the director of the
      Metropolitan Agency were interviewed, and records were analyzed from ten years of
      meetings of the Regional Inter-Administration Committee and the Regional
      Development Council. Four issues emerged: financing and infrastructure; health
      services utilization; inefficiency of the Regional Health Administration's
      instruments and decision-making levels; and the relationship between different
      levels in the Administration. Metropolitan health management remained as an
      underlying issue, appearing only incidentally or tangentially to regional
      management. Despite some limitations, the CGR has been legitimized as a space for
      regional health management.

PMID- 22641516
TI  - [Evaluation of the implementation of Kangaroo Care by health administrators,
      professionals, and mothers of newborn infants].
AB  - This was a qualitative evaluation study aimed at both shedding light on the
      challenges and facilitating implementation of Kangaroo Care in Ministry of Health
      accredited maternity care facilities in Brazil, from the standpoint of healthcare
      professionals and administrators and mothers of low birth weight newborns. Semi
      structured on-site interviews were conducted at the maternity centers. The study
      used structural narrative analysis with the data analysis method. Key evaluative
      focal points identified were the method's importance in neonatal care and
      institutional support for its sustainability. As for the findings, the
      theoretical concept of institutional analysis was essential for achieving more in
      depth reflection. Despite some resistance, the method is being implemented
      effectively in maternity care facilities; however, the study shows the need for
      periodic training and more resource allocation to enable improvement in the
      service's infrastructure, thereby resulting in more effective humanization of
      care.

PMID- 22641517
TI  - [Work days lost due to health problems in industry].
AB  - This cross-sectional study estimated the prevalence of work days lost due to
      health problems and associated factors among industrial workers. The study
      population was a simple random cluster sample of 3,403 workers from 16 to 65
      years of age in the city of Salvador, Bahia State, Brazil. Data were collected
      with individual home interviews. Among industrial workers, one-year prevalence of
      work days lost to health problems was 12.5%, of which 5.5% were directly work
      related and 4.1% aggravated by work. There were no statistically significant
      differences when compared to other worker categories. Self-perceived workplace
      hazards, history of work-related injury, and poor self-rated health were
      associated with work days lost due to work-related injuries/diseases. The
      findings showed that work days lost are common among both industrial and non
      industrial workers, thereby affecting productivity and requiring prevention
      programs.

PMID- 22641518
TI  - [The public healthcare system in the context of Brazil's demographic transition:
      current and future demands].
AB  - This paper assesses inpatient and outpatient care and their capacity to respond
      to changing demands in the context of the demographic transition in Brazil. The
      data were obtained from studies by the Brazilian Institute of Geography and
      Statistics (IBGE) and databases in the National Health System (CNES, SIH, and
      SIA). The reduction in birth, fertility, and infant mortality rates and the
      increase in life expectancy at birth are still driving population growth, while
      decreasing the dependency rate, thereby providing the opportunity to make
      necessary adjustments. The population increased by more than 27.5 million from
      1999 to 2009, with a 26.7% reduction in hospital beds and 947,000
      hospitalizations, with distortions in the distribution by specialty, but with
      increases in high-complexity outpatient and inpatient care. The results show that
      Brazil is undergoing a transition in the healthcare model, requiring greater
      capacity for future planning of a more complex system and revising the model to
      prepare for a larger elderly population in the coming decades.

PMID- 22641519
TI  - Association between periodontal disease and subclinical atherosclerosis: the ELSA
      Brasil study.
AB  - The aim of this study was to investigate the relationship between periodontal
      disease and increased thickness of the carotid artery intima-media complex. A
      cross-sectional study was conducted with 220 adults (age >= 35 years) among
      participants in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
      Carotid artery ultrasound and periodontal clinical examinations were conducted
      and included visible plaque index, gingival bleeding on probing index, probing
      pocket depth (PPD), and clinical attachment level (CAL). Individuals with
      increased carotid artery thickness showed fewer teeth and higher frequency of CAL
      >= 3mm, CAL >= 4mm, CAL >= 5mm, and CAL >= 6mm and PPD >= 4mm (p < 0.05). Despite
      the use of 18 definitions for periodontal disease, only one confirmed the
      hypothesis of an association between periodontal disease and subclinical
      atherosclerosis. Individuals with 10% or more sites with CAL >= 4mm were more
      likely to present carotid thickening.

PMID- 22641520
TI  - Socioeconomic status and age at menarche in indigenous and non-indigenous Chilean
      adolescents.
AB  - The objective was to analyze the relationship between socioeconomic status and
      age at menarche among indigenous and non-indigenous girls in the Araucania Region
      of Chile, controlling for nutritional status and mother's age at menarche. A
      total of 8,624 randomly selected girls from 168 schools were screened, resulting
      in the selection of 207 indigenous and 200 non-indigenous girls who had recently
      experienced menarche. Age at menarche was 149.6 +/- 10.7 months in the indigenous
      group and 146.6 +/- 10.8 months in the non-indigenous group. Among the non
      indigenous, the analysis showed no significant association between age at
      menarche and socioeconomic status. In the indigenous group, age at menarche among
      girls with low socioeconomic status was 5.4 months later than among those with
      higher socioeconomic status. There were no differences in nutritional status
      according to socioeconomic level. Obesity was associated with earlier menarche.
      Menarche occurred earlier than in previous generations. An inverse relationship
      between socioeconomic status and age at menarche was seen in the indigenous group
      only; low socioeconomic status was associated with delayed menarche, regardless
      of nutritional status or mother's age at menarche.

PMID- 22641521
TI  - [A proposal for using data from antimicrobial prescriptions: the EUREQA
      experience].
AB  - This study demonstrates that the use of information from medical prescriptions is
      essential for understanding the dynamics of community bacterial resistance. The
      resulting analysis can also influence and help establish more adequate public
      health policies on the control and optimization of antimicrobial use. The article
      demonstrates the use of a logical model developed by the EUREQA project for
      acquisition, classification, interpretation, and analysis of data from
      prescriptions for oral antimicrobial use.

PMID- 22641522
TI  - [Coverage of the Hospital and Outpatient Information Form (CIHA) using births
      recorded in the Information System on Live Births (SINASC), Brazil, 2006-2009].
AB  - The Brazilian Ministry of Health established mandatory completion of the Hospital
      and Outpatient Information Form (CIHA) in all the country's health services in
      order to monitor care funded by sources other than the Unified National Health
      System (SUS). Considering that data quality is essential, this study analyzed
      coverage of the CIHA in the States and Federal District, taking data from the
      Information System on Live Births (SINASC) from 2006 to 2009 as the standard.
      Coverage of the CIHA was low in nearly all of the States, corresponding to fewer
      than one-fourth of the births recorded in the SINASC, decreasing from 24.4% in
      2006 to 19.7% in 2009. There was a wide variation between the States, with the
      best results in Sao Paulo (71.9% in 2006; 46.4% in 2009), Rio Grande do Sul
      (35.8% in 2006; 29.5% in 2009), and Santa Catarina (31.6% in 2006; 37.7% in
      2009). The other States showed less than 20% coverage. Mechanisms for data
      collection and use of the CIHA to support decision-making are important for
      planning and evaluating healthcare.

PMID- 22641523
TI  - [Translation and cross-cultural adaptation of the Multiple Sclerosis Walking
      Scale (MSWS-12) into Brazilian Portuguese].
AB  - Poor walking performance is predictive of heart disease and osteoporosis and
      increases the risk of death in the elderly. Gait and vision have been identified
      as the most valuable physical functions according to multiple sclerosis patients'
      perceptions. The objective of this study was to perform a translation and cross
      cultural adaptation of the Multiple Sclerosis Walking Scale (MSWS-12) into
      Brazilian Portuguese. A study of cross-cultural adaptation was conducted in ten
      steps. Participation in the study included four translators, two back
      translators, twelve medical experts, twelve patients, twelve healthy subjects,
      and a Portuguese language expert. Only the question "Did standing make it more
      difficult to do things?" posed difficulty in the translation process. Maximum
      time for completion was less than three minutes (171 seconds). Internal
      consistency analyses showed high reliability (Cronbach's alpha = 0.94). The
      content validation and internal consistency stages were completed satisfactorily.

PMID- 22641524
TI  - Discounting phase 2 results when planning phase 3 clinical trials.
AB  - Sample size planning is an important design consideration for a phase 3 trial. In
      this paper, we consider how to improve this planning when using data from phase 2
      trials. We use an approach based on the concept of assurance. We consider
      adjusting phase 2 results because of two possible sources of bias. The first
      source arises from selecting compounds with pre-specified favourable phase 2
      results and using these favourable results as the basis of treatment effect for
      phase 3 sample size planning. The next source arises from projecting phase 2
      treatment effect to the phase 3 population when this projection is optimistic
      because of a generally more heterogeneous patient population at the confirmatory
      stage. In an attempt to reduce the impact of these two sources of bias, we adjust
      (discount) the phase 2 estimate of treatment effect. We consider multiplicative
      and additive adjustment. Following a previously proposed concept, we consider the
      properties of several criteria, termed launch criteria, for deciding whether or
      not to progress development to phase 3. We use simulations to investigate launch
      criteria with or without bias adjustment for the sample size calculation under
      various scenarios. The simulation results are supplemented with empirical
      evidence to support the need to discount phase 2 results when the latter are used
      in phase 3 planning. Finally, we offer some recommendations based on both the
      simulations and the empirical investigations.

PMID- 22641525
TI  - Enhanced anti-tumor and anti-angiogenic effects of metronomic cyclophosphamide
      combined with Endostar in a xenograft model of human lung cancer.
AB  - Standard chemotherapy for advanced NSCLC has reached a therapeutic plateau. More
      effective strategies must be explored. The purpose of this study was to evaluate
      the role of metronomic chemotherapy combined with an angiogenesis inhibitor in
      non-small cell lung cancer (NSCLC). A total of 114 BALB/c nude mice were
      inoculated subcutaneously with human NSCLC cells (A549), and when xenograft
      tumors were palpable, mice were randomly injected with saline as controls (Ctrl),
      or treated with metronomic cyclophosphamide (MET CPA), recombinant human
      endostatin, Endostar (Endo), MET CPA combined with Endostar (MET CPA+Endo) or
      maximum tolerance dose of CPA (MTD CPA), respectively. The growth of xenograft
      tumors and mouse survival were monitored. The frequency of peripheral blood
      circulating endothelial cells (CECs), microvessel density (MVD) and pericyte
      coverage was determined using flow cytometry and immunofluorescence staining. In
      comparison with the controls, treatment with either drug significantly inhibited
      the growth of xenograft tumors in mice. Treatment with MET CPA or Endostar, but
      not with MTD CPA, significantly reduced the frequency of peripheral blood total
      and viable CECs and the value of MVD. Endostar also considerably reduced pericyte
      coverage in xenograft tumors. Moreover, MET CPA combined with Endostar further
      reduced the frequency of peripheral blood CECs, the value of MVD, and pericyte
      coverage, with concomitant delay in tumor growth and extension of mouse survival.
      Our results indicate that MET CPA combined with Endostar results in enhanced anti
      tumor and anti-angiogenic effects in a xenograft model of human lung cancer.
      Combined therapy with metronomic chemotherapy and an angiogenesis inhibitor may
      serve as a promising treatment strategy for patients with advanced NSCLC.

PMID- 22641526
TI  - Exploitation of dinuclear salan aluminum complexes for versatile copolymerization
      of epsilon-caprolactone and L-lactide.
AB  - By combining the influence of excess alcohol, temperature and monomer-to
      initiator ratios in the feed, dinuclear salan aluminum complexes L(R)Al(2)Me(4)
      exhibited a high degree of control towards the copolymerization of L-LA and
      epsilon-CL, producing blocky, gradient, tapered and random copolymers.

PMID- 22641527
TI  - Relapse of liver amyloidosis 6 years after autologous stem cell transplantation.

PMID- 22641529
TI  - In situ synthesis of molecularly imprinted nanoparticles in porous support
      membranes using high-viscosity polymerization solvents.
AB  - There is a growing need in membrane separations for novel membrane materials
      providing selective retention. Molecularly imprinted polymers (MIPs) are
      promising candidates for membrane functionalization. In this work, a novel
      approach is described to prepare composite membrane adsorbers incorporating
      molecularly imprinted microparticles or nanoparticles into commercially available
      macroporous filtration membranes. The polymerization is carried out in highly
      viscous polymerization solvents, and the particles are formed in situ in the
      pores of the support membrane. MIP particle composite membranes selective for
      terbutylazine were prepared and characterized by scanning electron microscopy and
      N2 porosimetry. By varying the polymerization solvent microparticles or
      nanoparticles with diameters ranging from several hundred nanometers to 1 um
      could be embedded into the support. The permeability of the membranes was in the
      range of 1000 to 20,000 Lm-2  hr-1  bar-1. The imprinted composite membranes
      showed high MIP/NIP (nonimprinted polymer) selectivity for the template in
      organic media both in equilibrium-rebinding measurements and in filtration
      experiments. The solid phase extraction of a mixture of the template, its
      analogs, and a nonrelated compound demonstrated MIP/NIP selectivity and substance
      selectivity of the new molecularly imprinted membrane. The synthesis technique
      offers a potential for the cost-effective production of selective membrane
      adsorbers with high capacity and high throughput.

PMID- 22641530
TI  - Molecularly imprinted polymer sensors for detection in the gas, liquid, and vapor
      phase.
AB  - Fast, reliable, and inexpensive analytical techniques for detection of airborne
      chemical warfare agents are desperately needed. Recent advances in the field of
      molecularly imprinted polymers have created synthetic nanomaterials that can
      sensitively and selectively detect these materials in aqueous environments, but
      thus far, they have not been demonstrated to work for detection of vapors. The
      imprinted polymers function by mimicking the function of biological receptors.
      They can provide high sensitivity and selectivity but, unlike their biological
      counterparts, maintain excellent thermal and mechanical stability. The
      traditional imprinted polymer approach is further enhanced in this work by the
      addition of a luminescent europium that has been introduced into the polymers to
      provide enhanced chemical affinity as well as a method for signal transduction to
      indicate the binding event. The europium in these polymers is so sensitive to the
      bound target; it can distinguish between species differing by a single methyl
      group. The imprinted polymer technology is fiber optic-based making it
      inexpensive and easily integratable with commercially available miniature fiber
      optic spectrometer technologies to provide a shoebox size device. In this work,
      we will describe efforts to apply these sensors for detection of airborne
      materials and vapors. Successful application of this technology will provide
      accurate low level vapor detection of chemical agents or pesticides with little
      to no false positives.

PMID- 22641531
TI  - Responsive behavior of tumor-marker-imprinted hydrogels using macromolecular
      cross-linkers.
AB  - Tumor-marker-imprinted hydrogels having lectin and antibody molecules as ligands
      for a tumor-specific marker glycoprotein were strategically prepared by
      biomolecular imprinting using minute amounts of low-molecular-weight or high
      molecular-weight cross-linkers. The tumor-marker-imprinted hydrogels shrank
      gradually in response to a target glycoprotein, because their apparent cross
      linking density increased owing to simultaneous complex formation of lectin and
      antibody ligands with a target glycoprotein after their ligands dynamically
      recognized the glycoprotein. The swelling ratio of the tumor-marker-imprinted
      hydrogel using high-molecular-weight cross-linker with an optimal chain length
      decreased more drastically than that using a low-molecular-weight cross-linker,
      but the hydrogel using the cross-linker with a chain that was too long did not
      exhibit tumor-marker responsive behavior. This paper focuses on the effect of the
      molecular weight of cross-linkers on the responsive behavior of tumor-marker
      imprinted hydrogels having lectin and antibody molecules as ligands. The cross
      linker chain length was an important factor in determining the dynamic
      glycoprotein recognition and responsive behavior of the biomolecule-imprinted
      hydrogels.

PMID- 22641532
TI  - Towards water compatible MIPs for sensing in aqueous media.
AB  - When synthesizing molecularly imprinted polymers (MIPs), a few fundamental
      principles should be kept in mind. There is a strong correlation between porogen
      polarity, MIP microenvironment polarity and the imprinting effect itself. The
      combination of these parameters eventually determines the overall binding
      behavior of a MIP in a given solvent. In addition, it is shown that MIP binding
      is strongly influenced by the polarity of the rebinding solvent. Because the use
      of MIPs in biomedical environments is of considerable interest, it is important
      that these MIPs perform well in aqueous media. In this article, various
      approaches are explored towards a water compatible MIP for the target molecule l
      nicotine. To this end, the imprinting effect together with the MIP matrix
      polarity is fine-tuned during MIP synthesis. The binding behavior of the
      resulting MIPs is evaluated by performing batch rebinding experiments that makes
      it possible to select the most suitable MIP/non-imprinted polymer couple for
      future application in aqueous environments. One method to achieve improved
      compatibility with water is referred to as porogen tuning, in which porogens of
      varying polarities are used. It is demonstrated that, especially when multiple
      porogens are mixed, this approach can lead to superior performance in aqueous
      environments. Another method involves the incorporation of polar or non-polar
      comonomers in the MIP matrix. It is shown that by carefully selecting these
      monomers, it is also possible to obtain MIPs, which can selectively bind their
      target in water.

PMID- 22641533
TI  - Modulation of imprinting efficiency in nanogels with catalytic activity in the
      Kemp elimination.
AB  - The interactions between the template and the functional monomer are a key to the
      formation of cavities in the imprinted nanogels with high molecular recognition
      properties. Nanogels with enzyme-like activity for the Kemp elimination have been
      synthesized using 4-vinylpyridine as the functional monomer and indole as the
      template. The weak hydrogen bond interaction in the complex is shown to be able
      to induce very distinctive features in the cavities of the imprinted nanogels.
      The percentage of initiator used in the polymerisation, ranging from 1% to 3%,
      although it does not have a substantial effect on the catalytic rate, reduces
      considerably the imprinting efficiency. The alteration of the template/monomer
      ratio is also investigated, and the data show that there is considerable loss of
      imprinting efficiency. In terms of substrate selectivity, a number of experiments
      have been performed using 5-Cl-benzisoxazole as substrate analogue, as well as 5
      nitro-indole as template analogue for the preparation of a different set of
      nanogels. All the kinetic data demonstrate that the chemical structure of the
      template is key to the molecular recognition properties of the imprinted nanogels
      that are closely tailored and able to differentiate among small structural
      changes.

PMID- 22641534
TI  - The role of living/controlled radical polymerization in the formation of improved
      imprinted polymers.
AB  - In this work, living/controlled radical polymerization (LRP) is compared with
      conventional free radical polymerization in the creation of highly and weakly
      cross-linked imprinted poly(methacrylic acid-co-ethylene glycol dimethacrylate)
      networks. It elucidates, for the first time, the effect of LRP on the chain level
      and begins to explain why the efficiency of the imprinting process is improved
      using LRP. Imprinted polymers produced via LRP exhibited significantly higher
      template affinity and capacity compared with polymers prepared using conventional
      methods. The use of LRP in the creation of highly cross-linked imprinted polymers
      resulted in a fourfold increase in binding capacity without a decrease in
      affinity; whereas weakly cross-linked gels demonstrated a nearly threefold
      increase in binding capacity at equivalent affinity when LRP was used. In
      addition, by adjusting the double bond conversion, we can choose to increase
      either the capacity or the affinity in highly cross-linked imprinted polymers,
      thus allowing the creation of imprinted polymers with tailorable binding
      parameters. Using free radical polymerization in the creation of polymer chains,
      as the template-monomer ratio increased, the average molecular weight of the
      polymer chains decreased despite a slight increase in the double bond conversion.
      Thus, the polymer chains formed were shorter but greater in number. Using LRP
      neutralized the effect of the template. The addition of chain transfer agent
      resulted in slow, uniform, simultaneous chain growth, resulting in the formation
      of longer more monodisperse chains. Reaction analysis revealed that propagation
      time was extended threefold in the formation of highly cross-linked polymers when
      LRP techniques were used. This delayed the transition to the diffusion-controlled
      stage of the reaction, which in turn led to the observed enhanced binding
      properties, decreased polydispersity in the chains, and a more homogeneous
      macromolecular architecture.

PMID- 22641535
TI  - Controlling size and uniformity of molecularly imprinted nanoparticles using
      auxiliary template.
AB  - Molecularly imprinted nanomaterials are gaining substantial importance. As a
      simple and efficient synthetic method, precipitation polymerization has been used
      to prepare uniform molecularly imprinted microspheres for numerous template
      compounds. Despite of its general applicability, the difficulty of obtaining
      uniform particles for some difficult templates by precipitation polymerization
      has been reported. In this work, we attempted to produce uniform atrazine
      imprinted nanoparticles using propranolol as an auxiliary template under standard
      precipitation polymerization condition. When propranolol was added in the
      prepolymerization mixture for atrazine imprinting, it displayed a significant
      effect on particle size and size distribution of atrazine-imprinted polymers. The
      molecular binding characteristics of the molecularly imprinted polymer (MIP)
      nanoparticles were found to be dependent on the relative ratios of the two
      templates. Under an optimal template propranolol-atrazine ratio of 1:3 mol/mol,
      very uniform imprinted nanoparticles (d(H)  = 106 nm) with a polydispersity index
      of 0.07 were obtained. The loading of the auxiliary template (propranolol) could
      be reduced to as low as 5% without sacrificing the uniformity of the MIP
      nanoparticles. The uniform MIP nanoparticles could be easily encapsulated into
      polyethylene terephthalate nanofibers using a simple electrospinning technique.
      The composite nanofibers containing the MIP nanoparticles maintained specific
      molecular binding capability for both atrazine and propranolol.

PMID- 22641536
TI  - An innovative approach to molecularly imprinted capillaries for polar templates
      by grafting polymerization.
AB  - Molecularly imprinted polymers have been successfully used as selective
      stationary phases in capillary electrophoresis. Notwithstanding, this technique
      suffers from several drawbacks as the loss of molecular recognition properties in
      aqueous media and the lack of feasibility for imprinted systems directed towards
      highly polar templates soluble in aqueous environments only. Thus, the
      preparation of imprinted polymers for highly polar, water-soluble analytes,
      represents a challenge. In this work, we present an innovative approach to
      overcome these drawbacks. It is based on a surface molecular imprinting technique
      that uses preformed macromonomers as both functional recognition elements and
      cross-linking agents. A poly-2-hydroxyethyl-co-methacrylic acid linear polymer
      was grafted from the surface of silica capillaries. The grafted polymer was
      exhaustively esterified with methacrylic anhydride to obtain
      polyethylendimethacrylate-co-methacrylic acid linear chains. Then, as a proof of
      concept, an adequate amount of a very polar template like penicillin V was added
      in a hydro-organic mixture, and a thin layer of imprinted polymer was obtained by
      cross-linking the polymer linear chains. The binding behaviour of the imprinted
      and non-imprinted capillaries was evaluated in different separation conditions in
      order to assess the presence of template selectivity and molecular recognition
      effects. The experimental results clearly show that this innovative kind of
      imprinted material can be easily obtained in very polar polymerization
      environments and that it is characterized by enhanced molecular recognition
      properties in aqueous buffers and good selectivity towards the template and
      strictly related molecules.

PMID- 22641539
TI  - Did we pass the border? Routine multivessel intervention in STEMI patients.

PMID- 22641540
TI  - Antiarrhythmic potential of aldosterone antagonists in atrial fibrillation.
AB  - Upstream therapy is the promising issue in the treatment of atrial fibrillation
      (AF) especially in patients with arterial hypertension and heart failure. The
      possible beneficial effects of renin-angiotensin-aldosterone system blockade with
      ACE-inhibitors and angiotensin receptor antagonists in AF prevention have been
      demonstrated in experimental and clinical studies. There is growing mass of
      evidence, from both theoretical and experimental research studies, to suggest
      that upstream therapy using spironolactone or eplerenone may reduce the
      deleterious effect of excess aldosterone secretion and further modify the
      environment of AF including inhibition of atrial muscle fibrosis. It refers to
      patients with different forms of AF, including chronic AF. Aldosterone
      antagonists treatment may be a simple and valuable additional option in low-risk,
      hypertensive and heart failure patients in primary and secondary prevention of
      refractory paroxysmal and persistent AF.

PMID- 22641541
TI  - Updated evidence on intracoronary abciximab in ST-elevation myocardial
      infarction: a systematic review and meta-analysis of randomized clinical trials.
AB  - BACKGROUND: Intracoronary (IC) abciximab administration remains a promising
      approach aimed to increase a drug concentration in the target area and possibly
      improve clinical outcomes in the setting of ST-segment elevation myocardial
      infarction (STEMI). The goal of this literature review and meta-analysis is to
      update available knowledge comparing IC and intravenous (IV) abciximab
      administration in STEMI patients. METHODS: A total of 7 randomized clinical
      trials (RCTs) with a median follow-up of 3 months were included in the meta
      analysis (n = 3311). All-cause mortality was selected as the primary end point
      while recurrent myocardial infarction (re-MI), target vessel revascularization
      (TVR) and major bleeding complications were the secondary end points. RESULTS: IC
      abciximab did not provide any benefits in terms of all-cause mortality as
      compared with IV abciximab (odds ratio [OR] 0.67; 95% confidence interval [CI]
      0.34-1.34). However, this neutral effect was driven by the AIDA STEMI trial. The
      IC route was associated with a reduced rate of re-MI when compared with IV
      administration (OR 0.61; 95% CI 0.40-0.92) but the difference disappeared after
      one of the RCTs was excluded from the analysis. Both strategies were equal
      regarding TVR (OR 0.66; 95% CI 0.40-1.09) and major bleeding complications (OR
      1.18; 95% CI 0.76-1.83). CONCLUSIONS: Our updated meta-analysis shows that the
      clinical superiority of IC over IV abciximab administration in STEMI patients is
      no longer clear after the release of the AIDA STEMI trial results. Further
      research in high-risk STEMI patients is warranted to finally determine clinical
      advantages of IC vs IV abciximab administration.

PMID- 22641542
TI  - How to do: telerehabilitation in heart failure patients.
AB  - According to the present guidelines for heart failure patients, regular exercise
      training has  obtained the class of recommendation I, level of evidence A.
      Despite the benefits of cardiac  rehabilitation, many heart failure patients are
      inactive. Common patient's rejection of existing  forms of rehabilitation and
      limitations resulting from the disease itself hinder the outpatient  cardiac
      rehabilitation. That is why home telerehabilitation seems to be the optimal form
      of  physical activity for heart failure patients.

PMID- 22641543
TI  - Relationship between psychosocial status, diabetes mellitus, and left ventricular
      systolic function in patients with stable multivessel coronary artery disease.
AB  - BACKGROUND: Negative emotional conditions contribute to the development of
      coronary artery disease (CAD). Depression and anxiety are prognostic factors in
      patients with CAD. The aim of our study was to investigate the association
      between emotional conditions and left ventricular (LV) systolic functions in CAD.
      METHODS: 168 patients (102 men, 66 women, mean age 66.3 +/- 9.9 years) with
      stable angina and multivessel disease (MVD) were included in the study. According
      to the LV ejection fraction (LVEF) in echocardiography, patients were divided
      into two groups, the preserved group (LVEF > 50%), and the impaired group (LVEF <
      50%). The preserved group consisted of 94 patients and the impaired group
      consisted of 74 patients. Emotional status was evaluated using the Hamilton
      Depression (HAM-D), Hamilton Anxiety (HAM-A), Beck Depression Inventory (BDI),
      and Beck Anxiety Inventory (BAI) scores. RESULTS: The prevalence of diabetes
      mellitus (DM) was significantly higher in the impaired group than in the
      preserved group (29.8% vs 56.8%, p < 0.01). The HAM-D, HAM-A, BAI and BDI scores
      were higher in the impaired group compared to the preserved group (HAM-D: 12.1 +/
      3.3 vs 14.5 +/- 2.3, p = 0.03; HAM-A: 12.7 +/- 3.4 vs 14.3 +/- 2.2, p = 0.01;
      BAI: 18.6 +/- +/- 6.4 vs 22.1 +/- 6.6, p = 0.01 and BDI: 13.9 +/- 2.5 vs 17.2 +/-
      2.0, p = 0.002, respectively). In multivariate analysis, BDI scores (odds ratio
      [OR]: 2.197, < 95% confidence interval [CI] 1.101-4.387; p = 0.026), HAM-A scores
      (OR: 1.912, < 95% Cl 1.092-2.974; p = 0.041) and DM (OR: 2.610, < 95% Cl 1.313
      5.183; p = 0.006) were important risk factors for LV dysfunction in stable
      patients with MVD. CONCLUSIONS: This study demonstrated that emotional status and
      DM are factors associated with impaired LV systolic function in patients with
      stable CAD.

PMID- 22641544
TI  - Comparison of infarct-related artery vs multivessel revascularization in ST
      segment elevation myocardial infarction with multivessel disease: analysis from
      Korea Acute Myocardial Infarction Registry.
AB  - BACKGROUND: Many ST-segment elevation myocardial infarction (STEMI) patients have
      multivessel disease. There is still controversy in treatment strategy in STEMI
      patients with multivessel disease. We compared clinical outcomes of multivessel
      revascularization with infarct- related artery (IRA) revascularization in STEMI
      patients. METHODS: The 1,644 STEMI patients with multivessel disease (1,106 in
      IRA group, 538 in multivessel group) who were received primary percutaneous
      coronary intervention (PCI) were analyzed from a nationwide Korea Acute
      Myocardial Infarction Registry. Primary endpoint was 12-month major adverse
      cardiac events (MACE, defined as death, myocardial infarction, and repeated
      revascularization). Secondary endpoints were 1-month MACE and each component,
      stent thrombosis during 12 month follow-up, and each components of the 12-month
      MACE. RESULTS: There were more patients with unfavorable baseline conditions in
      IRA group. 12-month MACE occurred in 165 (14.9%) patients in IRA group, 81
      (15.1%) patients in multivessel group (p = 0.953). There were no statistical
      significance in the rate of 1-month MACE, each components of 1-month MACE, and
      stent thrombosis during 12 month follow-up. Each components of 12-month MACE were
      occurred similarly in both groups except for target lesion revascularization
      (2.4% in IRA group vs 5.9% in multivessel group, p < 0.0001). After adjusting for
      confounding factors, multivessel revascularization was not associated with
      reduced 12-month MACE (OR 1.096, 95% CI 0.676-1.775, p = 0.711). CONCLUSIONS:
      There were no significant differences in clinical outcomes between both groups
      except for high risk of target lesion revascularization in multivessel
      revascularization group.

PMID- 22641546
TI  - Is routine echocardiography necessary after catheter ablation of atrioventricular
      nodal re-entrant tachycardia?
AB  - BACKGROUND: The aim of this study was to investigate whether pericardial effusion
      (PE) detected by transthoracic echocardiography (TTE) was clinically significant
      and whether routine echocardiography was necessary after catheter ablation of
      atrioventricular nodal re-entrant tachycardia (AVNRT). METHODS: A total of 202
      patients with AVNRT were included in the study from three centers. The patients
      received basic electrophysiology-guided therapy, followed by radiofrequency
      ablation (RFA). All patients underwent TTE before and after RFA therapy. RESULTS:
      The mean age of the study population was 46.2 +/- 17.9 and 30.7% of the patients
      were male. Of these patients, six (3%) had postoperative PE, as detected by TTE.
      However, none of them had cardiac tamponade (CT). Four patients had minimal PE,
      while two had mild PE. Repeated TTE at one to three months showed resolved PE. No
      significant difference was seen among the patients with and/or without PE in
      terms of age, gender, the number of RFA applications, or RFA duration; however,
      significantly prolonged duration of fluoroscopy exposure was observed in the
      patients with PE. CONCLUSIONS: PE was detected in 3% of the patients by TTE and
      associated with prolonged duration of fluoroscopy exposure. However, no patients
      with moderate or large PE or cardiac tamponade were found in the study. In
      conclusion, we suggest that TTE should only be performed in the presence of
      clinical indications following ablation of AVNRT.

PMID- 22641545
TI  - Significance of high sensitivity C-reactive protein and D-dimer in evaluating
      intracardiac thrombus and spontaneous echo contrast in patients referred for
      transesophageal echocardiography: a prospective study.
AB  - BACKGROUND: Intra-cardiac thrombus (ICT) and spontaneous echo contrast (SEC) are
      considered hypercoagulable and inflammatory conditions. We aimed to determine if
      high sensitivity C-reactive protein (CRP) and D-dimer (DD), in combination with
      variables of lower thrombotic risk (normal ejection fraction [NEF], sinus rhythm
      [NSR]), may predict the absence of ICT/SEC. METHODS AND RESULTS: Consecutive
      patients referred for transesophageal echocardiogram (TEE) for evaluation of
      cardioembolic source were prospectively enrolled. CRP and DD levels were
      determined at the time of TEE. 124 patients were enrolled, of whom 21 had
      ICT/SEC. The combination of NSR/NEF had a negative predictive value (NPV) of
      98.6% for absence of ICT/SEC. The NPVs of CRP and DD were 93.6% and 85%,
      respectively. Adding either CRP or DD to NSR/NEF combination increased the NPV to
      100%. Log CRP was significantly associated with ICT/SEC. CONCLUSIONS: The
      presence of NSR and NEF may defer the need for TEE for ICT/SEC evaluation. CRP
      association with ICT/SEC suggests that inflammation plays a role in ICT/SEC
      formation. Whether CRP and DD should become routine in the triage process of TEE
      for ICT/SEC evaluation requires further large scale prospective studies.

PMID- 22641547
TI  - Coronary artery fistula: review of 54 cases from single center experience.
AB  - BACKGROUND: Demographic and clinical characteristics and angiographic findings of
      Turkish patients with coronary artery fistula have been investigated in this
      study and diagnostic tests and treatment methods used in these patients have also
      been evaluated in detail. METHODS: We have examined the cardiac catheterization
      laboratory database retrospectively between March 2006 and July 2010. Among
      49,567 patients, we have noted 60 patients diagnosed as coronary artery fistula.
      After coronary angiographic images were evaluated by two invasive cardiologists,
      54 patients who had clear evidence of vessel of origin and drainage were included
      in the study. RESULTS: A total of 54 (0.1%) patients with coronary artery fistula
      were noted. Mean age was 56.7 +/- 10.7 years; 42 out of 54 patients had
      accompanying cardiac disorders. Patients complaints were directly associated with
      the presence of the fistula. Chest pain was the admission symptom in all of the
      patients with isolated coronary artery fistula. Six patients had coexistent
      congenital anomalies. Myocardial infarction with ST segment elevation occurred in
      11 of the patients. In contrast to the previous reports, the most common artery
      of origin of the fistula was left anterior descending artery (50.8%) and
      pulmonary artery was found to be the most frequent region of the fistula drainage
      by 53.7%. CONCLUSIONS: Our findings suggest that large fistulas originating from
      the proximal segments of coronary arteries may increase the likelihood of
      atherosclerosis and myocardial infarction even in asymptomatic patients with no
      evidence of ischemia in noninvasive tests and no dilatation of cardiac chambers,
      and should therefore be closed.

PMID- 22641548
TI  - Evaluation of left atrial mechanical functions and atrial conduction
      abnormalities in patients with clinical hypothyroid.
AB  - BACKGROUND: The aim of this study was to investigate left atrial (LA) mechanical
      functions, atrial electromechanical delay and P wave dispersion in hypothyroid
      patients. METHODS: Thirty-four patients with overt hypothyroid and thirty
      controls were included. A diagnosis of overt hypothyroid was reached with
      increased serum TSH and decreased free T4 (fT4) levels. LA volumes were measured
      using the biplane area length method and LA active and passive emptying volumes
      and fraction were calculated. Intra- and interatrial electromechanical delay
      (EMD) were measured by tissue Doppler imaging (TDI). P wave dispersion was
      calculated by 12 lead electrocardiograms. RESULTS: LA diameter were significantly
      higher in patients with overt hypothyroid (p = 0.021). LA passive emptying volume
      and LA passive emptying fraction were significantly decreased with hypothyroid
      patients (p = 0.002 and p < 0.001). LA active emptying volume and LA active
      emptying fraction were significantly increased with hypothyroid patients (p <
      0.001 and p < 0.001). Intra- and interatrial EMD, were measured significantly
      higher in hypothyroid patients (30.6 +/- 6.1 vs 18.0 +/- 2.7, p< 0.001; and 10.6
      +/- 3.4 vs 6.9 +/- 1.4, p < 0.001, respectively). P wave dispersion were
      significantly higher in hypothyroid patients (48.8 +/- 6.2 vs 44.3 +/- 7.2, p =
      0.022). In stepwise regression analysis demonstrated that, interatrial EMD and LA
      active emptying fraction related with TSH and fT4. CONCLUSIONS: This study showed
      that impaired LA mechanical and electromechanical function in hypothyroid
      patients. TSH and T4 were independent determinant of interatrial EMD and LA
      active emptying fraction.

PMID- 22641549
TI  - Atherosclerosis burden and coronary artery lesion complexity in acute coronary
      syndrome patients.
AB  - BACKGROUND: Syntax score (SS) is a prognostic marker in patients with acute
      coronary sydromes (ACS). Carotid intima media thickness (CIMT) and cardio ankle
      vascular index (CAVI) are well known surrogate marker of atherosclerosis burden.
      But association between atherosclerosis burden and coronary artery disease (CAD)
      complexity in ACS patients has not been investigated yet. METHODS AND RESULTS:
      Consecutive patients with first time diagnosis of ACS (n = 172) were enrolled.
      SS, a marker of CAD complexity, was assessed by dedicated computer software. CIMT
      was examined by B-mode ultrasound. CAVI was assessed by VaSera VS-1000 cavi
      instrument. SS for low, intermediate and high tertiles of CIMT value were 10.1 +/
      8.2 vs 11.4 +/- +/- 7.9 and 15.2 +/- 8.8; p = 0.02). SS for normal, borderline
      and abnormal CAVI values were 4 +/- 3.7 vs 11.1 +/- 7.2 and 14.1 +/- 9.1,
      respectively p = 0.009). Also, there was independent association between SS and
      CIMT (95% coinfidence interval [CI] 2.1-19, p = 0.014) and CAVI (95% CI 15-29, p
      = 0.021]. Neither traditional cardiovascular risk factor nor thrombolysis in
      myocardial infarction (TIMI) risk score was independent determinant of SS.
      CONCLUSIONS: We have shown that patients with higher atherosclerosis burden have
      more complex coronary artery lesions. Also these patients may be identified early
      by using surrogate markers of atherosclerosis. Its clinical significance requires
      further research.

PMID- 22641550
TI  - Evaluation of coronary artery abnormalities in Williams syndrome patients using
      myocardial perfusion scintigraphy and CT angiography.
AB  - BACKGROUND: Sudden death risk in Williams syndrome (WS) patients has been shown
      to be 25-100 times higher than in the general population. This study aims to
      detect coronary artery anomalies and myocardial perfusion defects in WS patients
      using noninvasive diagnostic methods. METHODS: This study features 38 patients
      diagnosed with WS. In addition to physical examination, electrocardiography, and
      echocardiography, computed tomography (CT) angiography and rest/dipyridamole
      stress technetium-99m sestamibi ((99m)Tc-sestamibi) single photon emission
      computed tomography (SPECT) myocardial perfusion scintigraphy (MPS) were
      performed. RESULTS: Twenty-one (55%) patients were male; 17 (45%) were female.
      The average patient age was 12 +/- 5 years (2.5-26 years); the average follow-up
      period was 7.2 +/- 4.2 years (6 months-18 years). Cardiovascular abnormalities
      were found in 89% of patients, the most common one being supravalvar aortic
      stenosis (SVAS). CT angiography revealed coronary anomalies in 10 (26%) patients,
      the most common ones being ectasia of the left main coronary artery and proximal
      right coronary artery as well as myocardial bridging. SVAS was present in 80% of
      patients with coronary artery anomalies. (99m)Tc-sestamibi SPECT MPS revealed
      findings possibly consistent with myocardial ischemia in 29% of patients, and
      ischemia in 7 out of 10 patients (70%) with coronary anomalies shown on CT
      angiography (p = 0.03). CONCLUSIONS: Coronary artery abnormalities are relatively
      common in WS patients and are often accompanied by SVAS. CT angiography and
      dipyridamole (99m)Tc-sestamibi SPECT MPS seem to be less invasive methods of
      detecting coronary artery anomalies and myocardial perfusion defects in WS
      patients.

PMID- 22641551
TI  - Simultaneous subacute thrombosis of bare metal coronary stents in two different
      arteries early after clopidogrel cessation.
AB  - Coronary stent thrombosis is a rare event leading to ST segment elevation
      myocardial infarction  and death. Although early thrombosis of drug-eluting and
      bare metal stents is relatively  frequent, simultaneous thrombosis of bare metal
      coronary stents has rarely been reported.  Here, we present a case of
      simultaneous subacute thrombosis of two bare metal stents in  different coronary
      arteries early after clopidogrel cessation.

PMID- 22641552
TI  - Left ventricular ballooning syndrome due to vasospasm of the middle portion of
      the left anterior descending coronary artery.
AB  - We report a case that shows vasospasm to be one of the mechanisms responsible for
      left ventricular  ballooning syndrome. Our case suggests that identical
      ventriculographic findings in patients  with tako-tsubo syndrome and those with
      coronary vasospasm of a long left anterior descending  artery coronary artery may
      be due to a common etiology.

PMID- 22641553
TI  - A giant pericardial cyst in an unusual localization.
AB  - Pericardial cysts are rareand benign lesions of the heart. They are usually
      asymptomatic and incidentally diagnosed on chest X-ray. Most are located at the
      right cardiophrenic angle. Life-threatening complications may be infrequently
      encountered. We report the case of a 54 year-old male with acute coronary
      syndrome and a pericardial cyst in an unusual localization.

PMID- 22641554
TI  - Sustained monomorphic left ventricular outflow tract tachycardia early after
      aortic valve replacement.
AB  - Sustained monomorphic ventricular tachycardia (VT) after valve surgery is
      uncommon. Cases  of focal VT or bundle-branch re-entry after aortic valve surgery
      have been reported. We present  the case of a 60 year-old patient with an
      incessant outflow tract VT early after aortic valve  replacement. We suggest the
      disease process affecting the valve and adjacent area, and/or the  surgical
      procedure, might somehow relate to VT substrate adjacent to the aortic annulus.

PMID- 22641555
TI  - Intramural hemotoma presenting as acute coronary syndrome: the importance of
      intravascular ultrasound.
AB  - Intramural hematoma in major coronary epicardial vessels is a rare cause of chest
      pain. Afflicted  individuals may present with acute coronary syndrome (ACS) or
      even sudden cardiac  death. Spontaneous, isolated intramural hematoma may occur
      in the absence of associated  intimal dissection. In this situation, lesions may
      be angiographically indistinguishable from  ruptured atherosclerotic plaque.
      Intravascular ultrasound is important in the accurate diagnosis  of isolated
      intramural hematoma. Although coronary stenting may be required in the presence
      of  ongoing ischemia, intramural hematoma may be successfully managed medically.
      We describe  the case of a middle-aged woman who presented with ACS due to an
      intramural hematoma and  discuss the diagnosis and management of this rare
      illness.

PMID- 22641556
TI  - Perforation by permanent pacemaker lead: how late can they occur?
AB  - Perforation by permanent pacemaker lead is rare but does occur. Usually
      perforations happen  soon after the procedure, mostly within one year. But
      rarely, they occur late. We report a case of  delayed perforation by passive
      fixation lead 33 weeks after the implantation in a patient with  no
      comorbidities. The patient remained asymptomatic regarding the perforation except
      for  having the features of pacing failure.

PMID- 22641557
TI  - 'No-reflow' phenomenon.

PMID- 22641558
TI  - Accelerated idioventricular rhythm associated with propranolol treatment in a
      child.
AB  - Accelerated idioventricular rhythm (AIVR) is a ventricular arrhythmia most
      commonly seen  in adults with underlying cardiac disease. It is important to
      establish the diagnosis when it  occurs to differentiate this benign phenomenon
      from dangerous ventricular tachycardia.  We present the case of a healthy child
      who developed episodes of AIVR associated with propranolol  treatment. Her 24
      hour electrocardiography recording showed AIVR with difference  between sinus and
      ventricular beats. The arrhythmia resolved with the discontinuation of 
      propranolol, and eventually the case was in sinus rhythm. This patient is the
      first case of AIVR  associated with propranolol treatment in the literature.

PMID- 22641559
TI  - Selenium promotes proliferation of chondrogenic cell ATDC5 by increment of
      intracellular ATP content under serum deprivation.
AB  - Selenium (Se) is an essential micronutrient, and low Se intake in Se-deficient
      areas plays roles in an endemic osteochondropathy characterized by
      chondronecrosis in growth plate and articular cartilage. However, the biological
      activities of Se on cartilage are largely unknown. In this study, we examined the
      effects of Se on chondrogenic cell ATDC5 and the possible mechanisms involved. We
      demonstrated that Se stimulated ATDC5 cell proliferation under serum deprivation
      but not routine culture. Furthermore, Se promoted G1-phase cell cycle progression
      along with induction of cyclin D1 expression at the mRNA and protein level.
      Moreover, Se increased intracellular ATP content and decreased intracellular
      superoxide anion concentration without affecting intracellular redox status as
      estimated by ratio of the reduced and oxidized glutathione. In addition,
      suppression of intracellular ATP synthesis by glycolysis inhibitor or
      mitochondrial uncoupler both abrogated Se-mediated cyclin D1 induction. These
      findings suggest Se stimulates proliferation of chondrogenic cell ATDC5 through
      acceleration of cell cycle progression accompanied with cyclin D1 induction by
      enhancement of intracellular ATP content. This novel finding provides evidence
      for a role of Se in cartilage formation and degenerative processes and further
      supports the relationship between Se status and cartilage function that may lead
      to better utilization of Se for cartilage homeostasis.

PMID- 22641561
TI  - Changes in FDB and soleus muscle activity after a train of stimuli during upright
      stance.
AB  - BACKGROUND: Evidence of self-sustained muscle activation following a brief
      electrical stimulation has been reported in the literature for certain muscles.
      OBJECTIVES: This report shows that the foot muscle (Flexor Digitorum Brevis -
      FDB) shows a self-sustained increase in muscle activity during upright stance in
      some subjects following a train of stimuli to the tibial nerve. METHODS: Healthy
      subjects were requested to stand upright and surface EMG electrodes were placed
      on the FDB, Soleus and Tibialis Anterior muscles. After background muscle
      activity (BGA) acquisition, a 50 Hz train of stimuli was applied to the tibial
      nerve at the popliteal fossa. The root mean square values (RMS) of the BGA and
      the post-stimulus muscle activation were computed. RESULTS: There was a 13.8%
      average increase in the FDB muscle EMG amplitude with respect to BGA after the
      stimulation was turned off. The corresponding post-stimulus Soleus EMG activity
      decreased by an average of 9.2%. We hypothesize that the sustained contraction
      observed in the FDB following stimulus may be evidence of persistent inward
      currents (PIC) generated in FDB spinal motoneurons. The post-stimulus decrease in
      soleus activity may have occurred due to the action of inhibitory interneurons
      caused by the PICs, which were triggered by the stimulus train. CONCLUSIONS:
      These sustained post-stimulation changes in postural muscle activity, found in
      different levels in different subjects, may be part of a set of possible
      responses that contribute to overall postural control.

PMID- 22641560
TI  - Conformational selection and induced changes along the catalytic cycle of
      Escherichia coli dihydrofolate reductase.
AB  - Protein function often involves changes between different conformations. Central
      questions are how these conformational changes are coupled to the binding or
      catalytic processes during which they occur, and how they affect the catalytic
      rates of enzymes. An important model system is the enzyme dihydrofolate reductase
      (DHFR) from Escherichia coli, which exhibits characteristic conformational
      changes of the active-site loop during the catalytic step and during unbinding of
      the product. In this article, we present a general kinetic framework that can be
      used (1) to identify the ordering of events in the coupling of conformational
      changes, binding, and catalysis and (2) to determine the rates of the substeps of
      coupled processes from a combined analysis of nuclear magnetic resonance R(2)
      relaxation dispersion experiments and traditional enzyme kinetics measurements.
      We apply this framework to E. coli DHFR and find that the conformational change
      during product unbinding follows a conformational-selection mechanism, that is,
      the conformational change occurs predominantly prior to unbinding. The
      conformational change during the catalytic step, in contrast, is an induced
      change, that is, the change occurs after the chemical reaction. We propose that
      the reason for these conformational changes, which are absent in human and other
      vertebrate DHFRs, is robustness of the catalytic rate against large pH variations
      and changes to substrate/product concentrations in E. coli.

PMID- 22641562
TI  - Decisional tool to assess current and future process robustness in an antibody
      purification facility.
AB  - Increases in cell culture titers in existing facilities have prompted efforts to
      identify strategies that alleviate purification bottlenecks while controlling
      costs. This article describes the application of a database-driven dynamic
      simulation tool to identify optimal purification sizing strategies and visualize
      their robustness to future titer increases. The tool harnessed the benefits of
      MySQL to capture the process, business, and risk features of multiple
      purification options and better manage the large datasets required for
      uncertainty analysis and optimization. The database was linked to a discrete
      event simulation engine so as to model the dynamic features of biopharmaceutical
      manufacture and impact of resource constraints. For a given titer, the tool
      performed brute force optimization so as to identify optimal purification sizing
      strategies that minimized the batch material cost while maintaining the schedule.
      The tool was applied to industrial case studies based on a platform monoclonal
      antibody purification process in a multisuite clinical scale manufacturing
      facility. The case studies assessed the robustness of optimal strategies to batch
      to-batch titer variability and extended this to assess the long-term fit of the
      platform process as titers increase from 1 to 10 g/L, given a range of equipment
      sizes available to enable scale intensification efforts. Novel visualization
      plots consisting of multiple Pareto frontiers with tie-lines connecting the
      position of optimal configurations over a given titer range were constructed.
      These enabled rapid identification of robust purification configurations given
      titer fluctuations and the facility limit that the purification suites could
      handle in terms of the maximum titer and hence harvest load.

PMID- 22641563
TI  - Three patients with Wolf-Hirschhorn syndrome carrying a satellited chromosome 4p.
AB  - BACKGROUND: Wolf-Hirschhorn syndrome (WHS) is caused by a deletion involving the
      4p16.3 region. Approximately 70% of WHS patients have a de novo isolated deletion
      and 22% involve unbalanced translocations. However, WHS with unbalanced
      rearrangements involving the short arm of an acrocentric chromosome are
      infrequently reported. METHODS: Cytogenetic and molecular analyses by using
      standard G-banding, argyrophilic nucleolar organiser region (Ag-NOR) staining,
      fluorescence in situ hybridization, and single nucleotide polymorphism array for
      copy number detection were performed in three patients with WHS phenotype from
      two Chinese families. RESULTS: A heterozygous 2,767,380-bp terminal 4p deletion
      was detected in patients 1 and 2 and a heterozygous 5,047,291-bp terminal 4p
      deletion was detected in patient3. Clinical comparisons among our patients and
      previously reported cases have been reviewed. CONCLUSION: Two terminal 4p
      deletions were identified in three WHS patients with a satellited 4p and an
      attempt was made to refine the genotypic-phenotypic correlations of the deleted
      regions.

PMID- 22641565
TI  - Association of sleep disturbances with cognitive impairment and depression in
      maintenance hemodialysis patients.
AB  - BACKGROUND: There are few data on the relationship of sleep with measures of
      cognitive function and symptoms of depression in dialysis patients. METHODS: We
      evaluated the relationship of sleep with cognitive function and symptoms of
      depression in 168 hemodialysis patients, using multivariable linear and logistic
      regression. Sleep disturbances were assessed using the sleep subscale battery of
      the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Health Experience
      Questionnaire. The cognitive battery assessed a broad range of functioning
      including global ability, verbal intelligence, supraspan learning, auditory
      retention, visual retention, attention/mental processing speed, visual
      construction/fluid reasoning and motor speed. Depressive symptoms were assessed
      using the Center for Epidemiological Studies of Depression (CESD) Scale, with
      depression indicated by a CESD score >16. RESULTS: Mean (SD) age of participants
      was 62 (17) years, 49% were women, 30% were African American and 33% had
      diabetes. There was no significant relationship between sleep score and
      performance on any neurocognitive test (p>0.13, for all multivariable analyses).
      The prevalence of depression increased from 16% in the highest quartile (best) of
      sleep score, to 31% in the lowest quartile (worst) of sleep score. In
      multivariable analyses, each 1 SD increase in sleep score was associated with a
      2.18 (95% confidence interval, 1.07-3.29, p<0.001) lower CESD score. Results were
      consistent when considering individual components of both the CESD and sleep
      score. CONCLUSIONS: Disturbances in sleep are associated with symptoms of
      depression but not measures of cognitive function. Dialysis patients with
      disturbances in sleep should be screened for depression.

PMID- 22641564
TI  - JAK2 and genomic instability in the myeloproliferative neoplasms: a case of the
      chicken or the egg?
AB  - The myeloproliferative neoplasms (MPNs) are a particularly useful model for
      studying mutation accumulation in neoplastic cells, and the mechanisms underlying
      their acquisition. This review summarizes our current understanding of the
      molecular defects present in patients with an MPN, and the effects of mutations
      targeting Janus kinase 2 (JAK2)-mediated intracellular signaling on DNA damage
      and on the elimination of mutation-bearing cells by programmed cell death.
      Moreover, we discuss findings that suggest that the acquisition of disease
      initiating mutations in hematopoietic stem cells of some MPN patients may be the
      consequence of an inherent genomic instability that was not previously
      appreciated.

PMID- 22641566
TI  - Drug use and iatrogenic illness in complex older adults with kidney disease.
AB  - The aging process is characterized by a high level of complexity, which makes the
      care of older adults particularly challenging. This complexity results from the
      presence of an array of concomitant clinical conditions, whose integration and
      cumulative effect result in different degrees of functional deficits, cognitive
      deterioration, nutritional problems, geriatric syndromes in addition to lack of
      social support and financial resources. The presence of these factors may reduce
      the efficacy of prescribed drugs and increase the risk of iatrogenic illness
      making the pharmacologic treatment of this complex patient a difficult task for
      the prescribing physician. The presence of renal disease further contributes to
      increasing this complexity and to increasing the risk of iatrogenic illness
      because it is associated with pharmacokinetics and pharmacodynamics that may
      alter drug metabolism. For this reason, a complete and global examination of
      patient characteristics is mandatory in the drug prescribing process. Assessment
      of renal function must be considered part of this process.

PMID- 22641567
TI  - The nephro-geriatric unit in a lean-oriented in-hospital model of care.
AB  - Nephrologists worldwide are gradually coping with elderly patients. This is
      because of the burden of chronic disease in the aging population and specifically
      chronic kidney disease (CKD). CKD in the elderly rarely occurs in isolation from
      other chronic conditions and can often be a marker of these conditions
      themselves. Geriatricians usually take care of chronic conditions and are trained
      to perform comprehensive geriatric assessment, a tool to estimate frailty, that
      is the risk of adverse outcome, disability, and death in the clinical setting of
      elderly inpatients. Unfortunately, they are not used to a CHD invasive and non
      invasive approach and so there is no doubt about the need for a co-managed care
      model for these patients. However, where and how this model must be realized is
      still questionable. New hospital care models are patient-centered and encompass
      the concepts of departments to embrace the differentiated levels of care
      approach. According to this model the hospital is subdivided into three different
      standards of care: 1-high; 2 -intermediate; 3- low and this organization avoids
      inpatients being transferred frequently to different units, receiving specific
      care easily obtained by moving and changing the medical staff in charge of the
      patient. The lean care approach integrates the principles of the Toyota Producing
      System (TPS), a leading system of the industrial world, into intensity-based
      hospital care, thereby maximizing quality processes and promoting co-managed care
      as in the nephro-geriatric clinical setting.

PMID- 22641568
TI  - Aldosterone mediates glomerular inflammation in experimental mesangial
      proliferative glomerulonephritis.
AB  - BACKGROUND: The renoprotection of the mineralocorticoid receptor antagonist (MRA)
      is considered to be mainly via its antifibrotic activity, and the possibility
      that it may also have antiinflammatory effects has not been studied. We tested
      the hypothesis that MRA might influence the inflammatory changes that accompany
      experimental glomerular injury. METHODS: Administration of vehicle (control) or a
      selective MRA, eplerenone (50 mg/kg x 2 times/day) was started 7 days (-7d)
      before induction of anti-Thy-1.1 glomerulonephritis. Kidney samples were
      evaluated serially over a 12-day period for the presence of cell proliferation,
      macrophage infiltration, mesangial cell phenotypic activation and expression of
      the chemokine monocyte chemoattractant protein-1 (MCP-1). RESULTS: MRA did not
      prevent the mesangiolysis associated with anti-Thy-1 antibody. However, MRA
      significantly inhibited MCP-1 expression, glomerular macrophage infiltration and
      mesangial phenotypic activation (alpha-smooth muscle actin expression).
      CONCLUSION: MRA alters glomerular inflammation and mesangial cell activation in
      experimental glomerular injury. MRA may be a novel way to treat acute glomerular
      diseases.

PMID- 22641569
TI  - HNF-1beta mutation affects PKD2 and SOCS3 expression causing renal cysts and
      diabetes in MODY5 kindred.
AB  - BACKGROUND: Maturity onset diabetes of young (MODY) type 5 is a form of non
      insulin-dependent diabetes mellitus associated with renal cysts. It is an
      autosomal dominant disorder caused by mutations in the gene encoding hepatocyte
      nuclear factor-1beta (HNF-1beta). METHODS: We performed molecular screening of
      HNF-1beta in a 13-year-old patient and his affected father, and analyzed
      polycystic kidney disease 2 (PKD2) gene and suppressor of cytokine signaling 3
      (SOCS3) expression in lymphoblastoid cell lines and lymphocytes from both
      patients. RESULTS: We found a novel HNF-1beta frameshift mutation (c.C1304del)
      that results in a truncated protein (p.I434IfsX1). The genetic change is
      localized in the transactivated protein domain. CONCLUSIONS: We demonstrated that
      this novel HNF-1beta mutation strongly influences the expression of both PKD2,
      responsible for the formation of the renal cysts, and SOCS3, which is associated
      with early diabetes onset.

PMID- 22641570
TI  - Clinical significance of IgM and C1q deposition in the mesangium in pediatric
      idiopathic nephrotic syndrome.
AB  - BACKGROUND: In biopsy-proven idiopathic nephrotic syndrome (INS), immunoglobulin
      M (IgM) and C1q are occasionally deposited in the mesangium. In pediatric
      nephrology, the significance of mesangial IgM or C1q deposits is controversial,
      based on previous reports. The aim of this study was to explore the clinical
      significance of mesangial IgM and/or C1q deposits in pediatric INS patients,
      especially the initial responses to steroids and final outcomes. METHODS: We
      reviewed the clinical courses of 70 children with steroid-dependent or steroid
      resistant INS who underwent a renal biopsy at our hospital from 1998 to 2010.
      There were 30 mesangial IgM immunofluorescence (IF)-positive (IgM+) children. The
      IgM+ group was compared with the IgM IF-negative (IgM-) group. In addition, we
      reviewed the clinical characteristics of 8 mesangial C1q IF-positive (C1q+)
      children. RESULTS: Of the 30 IgM+ children, 10 (33.3%) were steroid-dependent
      (IgM- group: 18/40, 45%) and 14 (46.7%) were steroid-resistant (IgM- group:
      11/40, 27.5%; p<0.05). Although a high frequency of steroid-resistant INS was
      observed in the IgM+ group, the efficacy of cyclosporine (CyA) therapy was
      relatively good (all 14 steroid-resistant children obtained complete or partial
      remission). Moreover, all 8 C1q+ children obtained complete remission after CyA
      therapy, although they had a high frequency of steroid resistance (7/8, 87.5%),
      and 1 child was steroid-dependent. CONCLUSIONS: Our results indicate that,
      regardless of the histological pattern (minimal change disease, focal segmental
      glomerulosclerosis or diffuse mesangial hypercellularity), children with IgM+
      and/or C1q+ INS have good responses to CyA. IgM+ and/or C1q+ may be markers of
      the initial disease severity of INS.

PMID- 22641571
TI  - Quantification of experimental acute kidney injury by computer-assisted imaging
      of lectin phytohemagglutinin E.
AB  - BACKGROUND: Acute kidney injury (AKI) in sepsis accompanied by functional
      impairment regularly lacks histologic pathology to a similar extent. Moderately
      reproducible - semi-quantitative - scoring systems still remain the method of
      choice to quantify the extent of experimental AKI. Our aim was to establish a
      rather simple, fast, and reproducible staining protocol to quantify loss of brush
      border (BB) in septic AKI. METHODS: Murine septic AKI was induced by cecal
      ligation and puncture (CLP) and kidneys were harvested 24 h later. Binding of
      Phaseolus vulgaris erythroagglutinin (PHA-E) was visualized by the ABC-GO method
      coupled to tetranitroblue tetrazolium (TNBT). The mean BB area of five randomly
      chosen, non-overlapping cortical fields was analyzed by customized planimetric
      software. RESULTS: We detected statistically significant differences in the
      BB/noBB pixel ratio between septic AKI, sham-operated animals, and healthy mice
      (CLP: 0.091 +/- 0.019; SHAM: 0.141 +/- 0.048, P<.001; HEALTHY controls: 0.266 +/-
      0.14 pixel ratio). Moreover, this ratio correlates with functional parameters of
      renal function (creatinine r=-0.37, BUN r=-0.54, P<.0001). CONCLUSIONS: Our
      results demonstrate that PHA-E lectin staining followed by planimetric
      quantification is a reliable tool to analyze loss of BB during experimental AKI.

PMID- 22641572
TI  - Dyslipidemia, statins, and CKD patients' outcomes - review of the evidence in the
      post-sharp era.
AB  - Hyperlipidemia in the general population is strongly associated with an increased
      incidence of major adverse cardiovascular (CV) events (MACE). It is well
      established that HMG-CoA reductase inhibitors (statins) reduce CV and all-cause
      mortality in the general population, as well as in patients with CV disease
      (CVD). However, such a finding has not been definitively confirmed in patients
      with chronic kidney disease (CKD). Given that CV risk gradually increases with
      increasing stages of CKD (and is even higher in dialysis patients), it is of
      major relevance and importance to identify whether CKD patients might also
      benefit from alteration of lipid fractions, and how this might best be achieved.
      Bearing in mind that animal model and preclinical evidence suggests dyslipidemia
      might also be a factor promoting worsening renal function, it could legitimately
      be asked whether treating it may also therefore have a nephroprotective effect.

PMID- 22641573
TI  - Fluvastatin inhibits high glucose-induced nuclear factor kappa B activation in
      renal tubular epithelial cells.
AB  - INTRODUCTION: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors have been shown to reduce the progression of renal disease independent
      of cholesterol-lowering effect, but the mechanism of the potential protective
      effect remains unclear. Here, we investigate the effect of fluvastatin on
      activation of nuclear factor-kappaB (NF-kappaB) induced by high glucose in rat
      kidney tubule epithelial cells in vivo and in vitro. METHODS: Streptozotocin
      (STZ)-induced uninephrectomized diabetic rats were treated daily with fluvastatin
      (4 mg/kg body weight) by gavage. In 8 weeks the animals were killed, and their
      urine and blood samples were collected. Blood glucose, blood lipid, the urinary
      excretion of N-acetyl-beta-D-glucosaminidase (NAG), albumin and creatinine were
      measured. Immunohistochemical staining of NF-kappaB in the tubulointerstitium was
      performed. Rat renal tubular epithelial cells (NRK-52E) were cultured under
      normal glucose, high glucose (HG) and HG with fluvastatin or SB202190 (a specific
      inhibitor of p38MAPK) or mevalonate. Electrophoretic mobility shift assay (EMSA)
      was used to detect NF-kappaB activation. Phosphorylation of cellular p38 mitogen
      activated protein kinase (p38MAPK) was determined by Western blot analysis.
      RESULTS: Compared with that in the control group, the expression of NF-kappaB
      increased in tubulointerstitium of experimental diabetic rats (p<0.01).
      Fluvastatin significantly inhibited NF-kappaB expression and reduced proteinuria
      (p<0.01). High glucose stimulated the DNA-binding activity of NF-kappaB and
      phosphorylation of p38MAPK in cultured NRK-52E cells (p<0.01). This stimulatory
      effect of high glucose on NF-kappaB was blocked by SB203580. Incubation of cells
      with fluvastatin significantly inhibited the high glucose-induced NF-kappaB
      activation in a dose-dependent (10-7 to 10-5 mol/L) manner (p<0.05). Exogenous
      mevalonate (10-4 mol/L) prevented the effect of fluvastatin on NF-kappaB
      activation. CONCLUSION: These results suggest that fluvastatin reduces high
      glucose-induced NF-kappaB activation via the p38MAPK pathway in renal tubular
      epithelial cells in vivo and in vitro. The effect is at least partly due to
      blocking the biosynthesis of mevalonate.

PMID- 22641574
TI  - Stent-grafts versus angioplasty and/or bare metal stents for failing
      arteriovenous grafts: a cross-over longitudinal study.
AB  - BACKGROUND: A well-established method to preserve failing synthetic arteriovenous
      grafts (AVGs) dialysis accesses is percutaneous transluminal angioplasty (PTA).
      Nevertheless, the one-year primary patency rate following PTA is approximately
      25%. This study was designed to compare the angiographic and clinical outcomes
      following stent-graft insertion versus angioplasty and/or bare metal stenting
      (BMS) of recurrently failing AVGs, because of anastomotic and/or venous outflow
      stenoses. METHODS: Self-expanding stent-grafts were deployed for the treatment of
      failing AVGs in case of recurrent stenosis after treatment with conventional
      angioplasty or bail-out BMS. Regular angiographic follow-up was scheduled every
      two months the first six months and every three months thereafter. Data from
      previous procedures on the same treatment site were retrieved from our database.
      Primary patency was defined as a functioning graft with a patent treatment site
      without angiographic restenosis >50% and without any subsequent repeat
      procedures. Outcome data were analyzed by Kaplan-Meier analysis. RESULTS: In
      total, 35 patients previously treated with angioplasty and/or BMS for the
      treatment of recurrent significant AVG stenosis (group PTA), underwent stent
      graft placement of the same treatment site (group SG). Of those, 20 patients had
      undergone angioplasty and 15 bail-out BMS. Mean lesion length was 4.8+/-1.7cm.
      Primary patency was significantly improved in the SG group (Hazard Ratio [HR] =
      0.2 [95% CI= 0.11-0.36], P=.0001) by log-rank test. The estimated six and 12
      month patency rates were 76.9% vs. 25.7%, and 61.4% vs. 8.6% for groups SG and
      PTA respectively, (P<.0001). CONCLUSIONS: Stent-graft placement significantly
      improves primary patency of anastomotic and venous outflow stenoses in
      recurrently failing prosthetic arteriovenous grafts.

PMID- 22641575
TI  - Pre-pregnancy counseling for women with chronic kidney disease.
AB  - Pre-pregnancy counseling should be available for all women with chronic kidney
      disease (CKD) so that conception occurs at the right time in the course of their
      disease and while they are on the right medications, with the aims of minimizing
      risks for both mother and fetus. Key areas to consider are the factors which are
      associated with worse prognosis and the influence of underlying kidney conditions
      and their treatment, in particular lupus nephritis, advanced renal impairment and
      transplantation. This experience-based review provides a guide to clinicians
      managing women with CKD, before and during their pregnancy.

PMID- 22641576
TI  - Role of TGF-beta1 in production of fibronectin in vascular smooth muscle cells
      cultured under high-phosphate conditions.
AB  - BACKGROUND: Hyperphosphatemia is associated with up-regulation of the
      extracellular matrix formation in vascular smooth muscle cells (VSMCs) and
      increased risk of cardiovascular disease. In the present study, the role of
      transforming growth factor-beta1 (TGF-beta1) in the production of fibronectin
      (FN) in vascular smooth muscle cells in high-phosphate environments was
      evaluated. METHODS: Rat VSMCs were stimulated by high levels of phosphate or TGF
      beta1 in vitro. Levels of FN, TGF-beta1, and TGF-beta1 type I receptor (TbetaRI)
      proteins were measured by Western blot and immunostaining. Levels of active TGF
      beta1 in the supernatant of the culture medium were detected by ELISA. RESULTS:
      Production of FN was increased after VSMCs were incubated under high-phosphate
      conditions (2.5 mmol/L) for 12 hours. TGF-beta1 (1 ng/mL) increased FN levels in
      cells as early as 3 hours after the start of treatment. Both TGF-beta1 and
      TbetaRI were significantly up-regulated after 3-6 hours of stimulation with high
      phosphate. When VSMCs were pretreated with TGF-beta1 neutralization antibody (10
      ug/mL) for 30 minutes, induction of FN stimulated by high levels of phosphate was
      largely attenuated. CONCLUSION: TGF-beta1 plays a critical role in the
      pathogenesis of high-phosphate-induced FN production in VSMCs in vitro.

PMID- 22641577
TI  - Estimating the influence of physicians on the underuse of drugs in diabetic
      nephropathy in Taiwan.
AB  - BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin
      receptor blockers (ARBs) are widely recommended to hinder the progression of
      renal disease among patients with DM. However, little is known about adherence to
      these guidelines or the predictors of such use. METHODS: Data from the Taiwan
      National Health Insurance was used to investigate 7,186 DN patients, nested
      within 2960 randomly assigned primary care physicians in Taiwan over the course
      of 1 year of treatment. Patient-level variables included gender, age, and co
      morbidity (i.e., coronary arterial disease, congestive heart failure,
      cerebrovascular disease, peripheral arterial disease, DM complications,
      albuminuria, anemia, hyperlipidemia, asthma, gout, and depression). Physician
      level variables included work experience, the area of specialization, and the
      level of the physicians working in the hospital. RESULTS: We determined that
      63.69% of the variation in the use of ACEIs or ARBs was at the within-physician
      level and 36.31% was at the between-physician level. Approximately 35.10 % of the
      total variation was explained by predictors related to patient characteristics.
      The likelihood of taking ACEIs or ARBs is significantly higher (12.92%) among
      male patients than females. Cardiologists and family doctors are more likely to
      prescribe ACEIs or ARBs in of doctors working in medical centers. CONCLUSIONS:
      Management of DN patients is less than optimal due to unfamiliarity on the part
      of physicians regarding treatment guidelines and a lack of awareness among the
      general population with regard to DN. Educational initiatives are required to
      ensure adherence to clinical practice guidelines in the evaluation and care of DN
      patients.

PMID- 22641578
TI  - Usefulness of the multidimensional prognostic index (MPI) in the management of
      older patients with chronic kidney disease.
AB  - In older patients, given the central role of prognosis in clinical decision
      making, there is an urgent need to develop accurate, validated, and rigorously
      tested prognostic indices. Current data suggest that in older patients not only
      physical but also psychological, cognitive, functional, nutritional, biological,
      and social factors may contribute to the increased risk of negative outcomes
      including institutionalization, hospitalization, and mortality. Recently, a
      Multidimensional Prognostic Index (MPI), derived from a standardized
      comprehensive geriatric assessment that included information from eight domains,
      i.e. basal and instrumental activities of daily living, cognitive and nutritional
      status, the risk for pressure sores, comorbidities, drug use, and co-habitation
      status was effective in predicting short- and long-term all-cause mortality risk
      in hospitalized patients with various acute and chronic conditions, including
      chronic kidney disease (CKD). In a consecutive cohort of patients with CKD the
      MPI accuracy in predicting mortality was significantly higher than the accuracy
      of the estimated glomerular filtration rate (eGFR). More recently, findings from
      hospital-based cohorts suggest that adding MPI information to the eGFR markedly
      improved the prediction of two-year all-cause mortality in older patients with
      CKD. While further studies are needed to assess the potential usefulness of this
      prognostic tool in clinical practice, a multidimensional assessment for all-cause
      mortality risk prediction should be considered in older patients with CKD. These
      findings support the concept that considering multidimensional aggregate
      information is very important for predicting short- and long-term all-cause
      mortality in older subjects with CKD, and that it may be important for the
      identification of more suitable management of these patients.

PMID- 22641579
TI  - Women on hemodialysis have lower self-reported health-related quality of life
      scores but better survival than men.
AB  - BACKGROUND: Hemodialysis patients suffer from poor quality of life and survival.
      A retrospective cohort study was performed to examine the sex differences in self
      reported quality of life and mortality in a Taiwanese hemodialysis cohort.
      METHODS: A total of 816 stable hemodialysis patients were included. Patients
      completed two questionnaires: the 36-item Short Form Health Survey Questionnaire
      (SF-36, Taiwan Standard Version 1.0) to assess health-related quality of life
      (HRQoL) and the Beck Depression Inventory (BDI, Chinese Version) to assess
      depressive mood. Mortality outcomes were recorded for a seven-year follow-up
      period. RESULTS: After adjustment for confounding factors, women had
      significantly higher BDI scores (P=.003), lower physical functioning (P<.001),
      bodily pain (P<.001), mental health (P=0007), and physical component scale (PCS)
      scores (P<.001). There were 284 deaths recorded. In the Cox-proportional hazard
      model, women had significantly lower mortality than men (P<.001). CONCLUSIONS:
      Women on hemodialysis had more depression-related symptoms and poor self-reported
      HRQoL, but better survival than men. The sex difference in psychological and
      HRQoL issues deserves greater concern because this relates to clinical care and
      further study.

PMID- 22641580
TI  - Differential proteomic analysis of renal tissue in mesangial proliferative
      glomerulonephritis using iTRAQ technology.
AB  - BACKGROUND: Mesangial proliferative glomerulonephritis (MePGN) is characterized
      by excessive mesangial cell proliferation and mesangial matrix expansion, which
      lead to glomerular sclerosis and obliteration and, in turn, to deteriorating
      renal function. To identify and quantify the total proteins in renal tissues of
      MePGN patients, we used isobaric tags for relative and absolute quantification
      (iTRAQ) technology, and then looked for differentially expressed proteome
      profiles in MePGN patients. METHODS: Eight-plex iTRAQ coupled with multiple
      chromatographic fractionation and tandem mass spectrometry was used to analyze
      total proteins in renal tissues of MePGN patients. Proteins were identified using
      Mascot, compared to show any differential expression. RESULTS: Among 512 distinct
      proteins identified, 113 proteins were up-regulated or down-regulated with a
      onefold or more alteration in levels across groups. Among of them, there was
      significant variation in our present iTRAQ study, which contains lamin A, actin,
      profilin-1, annexin-A1 and A2 up-regulated, and antiquitin and aldolase B down
      regulated. CONCLUSION: iTRAQ-based quantitative proteomic technology is
      efficiently applicable for protein identification and relative quantitation of
      proteomes of renal tissue. Differentially expressed proteome profiles of MePGN
      patients are determined. Further investigation of the molecular mechanism of the
      involved proteins may help to better understand the pathogenesis of MePGN and to
      discover novel biomarker candidates, which may enable the development of new
      approaches to diagnosis of MePGN.

PMID- 22641581
TI  - Vitamin D2 versus vitamin D3 supplementation in hemodialysis patients: a
      comparative pilot study.
AB  - BACKGROUND: In patients with chronic kidney disease, vitamin D insufficiency is
      highly prevalent. It can be corrected by supplementation with either vitamin D(2)
      or vitamin D3. Recent studies in patients without impaired kidney function
      suggest that vitamin D(3) is more efficient than vitamin D(2) in correcting
      vitamin D insufficiency. However, no direct comparison has been made in
      hemodialysis (HD) patients. METHODS: Thirty-nine HD patients with serum 25
      hydroxyvitamin D (25(OH)D) levels =20 ng/mL were enrolled in this comparative,
      prospective pilot study. They were divided into 3 groups and treated over a 3
      month period. Each patient received oral doses of 200,000 international units
      (IU) vitamin D per month according to the following treatment schedule: (i)
      vitamin D(2) in small fractionated doses at each HD session, 3 times per week
      (group D2S); (ii) vitamin D(2) once a month (group D2M); or (iii) vitamin D(3)
      once a month (group D3M). Changes in serum 25(OH)D levels were measured at the
      end of the study. RESULTS: Posttreatment serum 25(OH)D levels increased
      significantly in all groups. The mean +/- SD serum 25(OH)D value for group D3M
      patients (40 +/- 13 ng/mL) was significantly higher than that for groups D2M (25
      +/- 9 ng/mL, p<0.01) and D2S patients (25 +/- 9 ng/mL, p<0.01). Serum 25(OH)D
      increased to levels >30 ng/mL in 84% of group D3M patients, but in only 15% and
      27% of group D2M and D2S subjects, respectively. CONCLUSION: Vitamin D(3) is more
      effective than vitamin D(2) in providing adequate 25(OH)D serum levels in HD
      patients.

PMID- 22641582
TI  - Metformin in patients with chronic kidney disease: strengths and weaknesses.
AB  - A wide array of benefits has been attributed to metformin. These include
      attenuation of abnormal glucose metabolism (diabetes treatment and prevention),
      weight neutrality or weight loss, improvement in the pathophysiologic components
      of metabolic syndrome (insulin resistance, subclinical inflammation, and
      endothelial dysfunction), lipid-lowering properties, cardiovascular protection,
      and antineoplastic potential. Metformin itself is not a nephrotoxic drug.
      Initially appointed as the safest hypoglycemic agent in chronic kidney disease,
      its use has been limited in these patients because of the perceived risk of
      lactic acidosis. A fear perpetuated by numerous case reports in which it is
      implicated. Current guidelines stipulate that it must be used with caution in
      estimated glomerular filtration rates (eGFRs) of less than 60 mL/minute and not
      at all in eGFRs of less than 30 mL/minute. Identified risk factors for metformin
      associated lactic acidosis include acute kidney injury, hypoxemia, sepsis,
      alcohol abuse, liver failure, myocardial infarction, and shock. Treatment may
      include supportive care and dialysis techniques. On the other hand, it is likely
      that the use of metformin would be beneficial in many with chronic kidney disease
      according to the advantages associated with attenuation of metabolic syndrome and
      cardiovascular protection. The reality of severe metformin-induced lactic
      acidosis in the absence of chronic renal impairment raises the question of
      limitation of its use in these patients.

PMID- 22641583
TI  - Hospital-acquired acute kidney injury in Chinese very elderly persons.
AB  - OBJECTIVES: To investigate the incidence, pathogenetic factors, the prognosis and
      correlation factors of the hospitalized very elderly patients(=80) with acute
      kidney injury (AKI). METHODS: The clinical data of the patients older than 80
      admitted in PLA General Hospital from June 1, 2008 to December 31, 2009 were
      collected. The patients with AKI were identified and their records of clinical
      characteristics were analyzed. RESULTS: The overall incidence of AKI in very
      elderly patients was 14.8%. Infection was the major cause of AKI in those
      patients. The multifactorial analysis showed that the most common causes of AKI
      were hypovolemia, nephrotoxic drugs, cardiac dysfunction and respiratory failure.
      Antibiotics were the most common factor in nephrotoxic drugs. Comparing with de
      novo AKI, the patients with Acute-on-Chronic AKI were older, the percent
      complication of multiple organ dysfunction syndrome (MODS), hyperlipidemia and
      the rate of recurring AKI was higher. Cox proportional hazard models showed
      variables of MODS, heart failure and gastrointestinal bleeding were independent
      risk factors for 90 days end outpoint, and MODS, malnutrition, gastrointestinal
      bleeding and absolute increase in SCR were independent risk factors for one year
      survival, the use of alpha-ketoacid was showed to be a protective factor(odd
      ratio=0.656). CONCLUSION: The incidence of AKI in the very elderly hospitalized
      patients was high. Infections, hypovolemia, nephrotoxic drugs and cardiovascular
      diseases were among the common causes. Active treatment of primary diseases,
      avoidance of complications and use of alpha-ketoacid were beneficial for
      improving the prognosis of the very elderly patients with AKI.

PMID- 22641584
TI  - Less invasive perinatal autopsies and the future of postmortem science.

PMID- 22641585
TI  - Rubella and autoimmunity.

PMID- 22641587
TI  - Stress perception and depressive symptoms: functionality and impact on the
      quality of life of women with fibromyalgia.
AB  - INTRODUCTION: Depression is one of the most frequent psychiatric comorbidities in
      patients with fibromyalgia (FM), and chronic stress might be one of the
      triggering events of the characteristic FM symptoms. OBJECTIVES: To compare
      depressive symptoms and stress perception between women with and without FM, in
      addition to investigate the relationship between those characteristics and the
      functionality and the impact on the quality of life of those patients. METHODS:
      The study included 20 women with FM (FM group) and 20 healthy women (control
      group). The following instruments were used: Beck Depression Inventory, Perceived
      Stress Scale-10, Health Assessment Questionnaire, Fibromyalgia Impact
      Questionnaire, and Visual Analogue Scale for pain (0-10 cm). RESULTS: The FM
      group showed higher severity of the depressive symptoms (24.10 +/- 11.68) and
      greater perception of stress (25.10 +/- 4.82) as compared with those of the
      control group (10.20 +/- 12.78, P < 0.01;and 15.45 +/- 7.29, P <
      0.01;respectively). A higher incidence of depressive symptoms was observed in the
      FM group (75%) than in the control group (25%) (chi2 = 10.00, P < 0.01). In the
      FM group, a positive correlation was observed between the depressive symptoms and
      perceived stress (r = 0.54, P < 0.05), pain (r = 0.58, P < 0.01), impaired
      functionality (r = 0.56, P < 0.01), and impact on the quality of life (r = 0.46,
      P < 0.05). In this group there was also correlation between perceived stress and
      impaired functionality (r = 0.50;P < 0.05). Pain showed no relationship with
      perceived stress. CONCLUSION: The relationship between stress, depression and
      functionality seems to be part of a complex mechanism, which might affect the
      quality of life of patients with FM.

PMID- 22641586
TI  - Prevalence of rubella serum antibody in autoimmune diseases.
AB  - INTRODUCTION: The association between infections and autoimmune diseases (AID)
      has been well described in the medical literature. Several infectious agents have
      been implicated as inducers of autoimmune responses, such as Parvovirus B19,
      Epstein-Barr virus, cytomegalovirus, and hepatitis viruses. PATIENTS AND METHODS:
      We examined 1,173 sera from patients with 14 different AID and 238 sera from
      geographically matched healthy controls, for evidence of prior infection with
      rubella. All samples were tested for the presence of serum antibodies against
      rubella using the Bio-Rad BioPlex 2200 system. RESULTS: As a group, patients with
      AID had a higher prevalence of IgM anti-rubella antibodies as compared to healthy
      controls (11.7% versus 5.4%; P = 0.001). The prevalence of IgM anti-rubella
      antibodies was significantly higher in 5/14 AID, namely in patients with giant
      cell arteritis (33.3%), primary biliary cirrhosis (24%), antiphospholipid
      syndrome (20.6%), polymyositis (16%), and inflammatory bowel disease (16%). A
      similar prevalence of IgM anti-rubella antibodies was detected among controls
      from different countries. A high prevalence of IgG anti-rubella antibodies was
      detected among patients with AID (89.9%) and controls. CONCLUSION: The increased
      prevalence of IgM anti-rubella antibodies in AID suggests a possible role for
      rubella in the etiopathogenesis of several AID.

PMID- 22641588
TI  - Frailty syndrome in the community-dwelling elderly with osteoarthritis.
AB  - OBJECTIVE: To characterize and compare community-dwelling elderly with knee
      and/or hip osteoarthritis (OA), focusing on the frailty syndrome. METHOD: Cross
      sectional study of the elderly with knee and/or hip OA, using a subsample from
      the study of frailty in the Brazilian elderly (FIBRA), assessing the following:
      sociodemographic characteristics, comorbidity, medications, depression,
      anthropomorphic data, falls, pain, stiffness, physical function, and frailty. The
      subjective assessment of health was also performed. RESULTS: The final sample
      comprised 58 elderly (mean age, 74 +/- 5.5 years) as follows: 17 (29.31%) non
      frail, 28 (48.28%) pre-frail, and 13 (22.41%) frail. The frail elderly received
      more medications than the non-frail ones (7.00 +/- 2.00 and 4.00 +/- 2.00,
      respectively; P = 0.001). The mean Body Mass Index was lower in the non-frail
      elderly as compared with those of the pre-frail and frail ones (27.00 +/- 4.50
      kg/m2, 30.00 +/- 4.00 kg/m2, and 34.00 +/- 8.00 kg/m2, respectively; P = 0.018).
      Depression was more prevalent in the frail group. Compared to the previous year,
      there was a difference in the health status of the groups as follows: 64.3% of
      the pre-frail elderly and 46.2% of the frail ones believed their health
      deteriorated, and 52.9% of the non-frail elderly considered that their health
      status remained unchanged (P = 0.016). When comparing the current physical
      activity levels with those of the previous year, the pre-frail and frail elderly
      reported a worsening (P = 0.010). Regarding physical function and fall-related
      self-efficacy, the frail elderly were worse than the others (P = 0.023 and 0.017,
      respectively). There were no significant differences between the groups for the
      remaining items analyzed. CONCLUSION: The elderly with OA and frailty use more
      medications, are more obese and depressed, have a poorer perception of their own
      health and of their level of activity as compared with that of the previous year,
      have a worse fall-related self-efficacy, and worse physical function.

PMID- 22641589
TI  - Validity and reliability of the Portuguese version of the American Shoulder and
      Elbow Surgeons Standardized Shoulder Assessment Form.
AB  - INTRODUCTION: The American Shoulder and Elbow Surgeons Standardized Shoulder
      Assessment Form (ASES), often used in research in Brazil, although translated and
      adapted to the Portuguese language, had not had its validity and reliability
      tested yet. OBJECTIVE: To assess the validity, reliability, and internal
      consistency of the ASES-PT for shoulder dysfunction. MATERIALS AND METHODS: Fifty
      individuals (26 women; mean age, 39 +/- 13 years) participated in the validity
      assessment, and 38 (19 women; mean age, 37 +/- 13 years old) in the reliability
      assessment, all having shoulder dysfunction. The participants completed the 36
      Item Short-Form Health Survey (SF-36), the Disabilities of the Arm, Shoulder and
      Hand Questionnaire (DASH), and the ASES-PT on two occasions with an interval of
      seven days. The convergent validity was assessed by use of the Spearman's rank
      correlation coefficient (rho), and the analysis of the intrarater reliability
      used the intraclass correlation coefficient (ICC). The internal consistency was
      assessed by using Cronbach's alpha. RESULTS: The ASES-PT scores correlated with
      the DASH scores (rho = -0.69, P = 0.000) and with the "physical functioning" (rho
      = 0.50, P = 0.000), "role limitation due to physical health" (rho = 0.43, P =
      0.002) and "bodily pain" domains (rho = 0.60, P = 0.000) of the SF-36. The
      intrarater reliability of the ASES-PT proved to be adequate (ICC = 0.75, P =
      0.000). The internal consistency (0.794) was satisfactory. CONCLUSION: The
      validity and reliability study of the ASES-PT supports its use for assessing
      shoulder dysfunction.

PMID- 22641590
TI  - Antinucleosome antibodies and primary antiphospholipid syndrome: an observational
      study.
AB  - OBJECTIVE: To study the association of anti-nucleosome (anti-NCS) antibodies in
      primary antiphospholipid syndrome (APS) and the development of systemic lupus
      erythematosus (SLE) during follow-up. MATERIALS AND METHODS: Thirty-six women
      with primary APS were evaluated prospectively for clinical features of systemic
      autoimmune diseases and for the presence of antiphospholipid antibodies,
      antinuclear antibodies and anti-NCS/chromatin antibodies. RESULTS: After a mean
      follow-up period of 45.7 months, anti-NCS/chromatin antibodies were detected in
      only one patient (2.8%), who developed features of SLE including polyarthritis,
      lymphopenia, optic neuritis, multiple sclerosis-like lesions, and an autoantibody
      profile suggestive of SLE. CONCLUSION: The frequency of anti-NCS/chromatin
      antibodies in primary APS patients is very low, and they may be associated with
      the development of SLE manifestations.

PMID- 22641591
TI  - Association of HLA-DRB5*01 with protection against cutaneous manifestations of
      rheumatoid vasculitis in Brazilian patients.
AB  - OBJECTIVE: To evaluate the frequency of HLA classes I and II and their
      association with the cutaneous manifestation of rheumatoid vasculitis (RV) in
      Brazilian patients. PATIENTS AND METHODS: During one year we selected 130
      patients with rheumatoid arthritis (RA) classified according to the American
      College of Rheumatology, 1987. All patients underwent a clinical and laboratory
      questionnaire to exclude other causes of cutaneous vasculopathy (neoplasia,
      infections, illicit drug use, diabetes mellitus, and tobaccoism). Seventy-three
      patients with any risk factor for other causes of vasculopathy were excluded.
      Fifty-seven without risk factors for other causes of vasculopathy were included
      in the study, 17 with RV according to Scott and Bacon's criteria, 1984.
      Demographic data, time of RA diagnosis, disease activity (DAS28), presence of
      rheumatoid factor, and anti-cyclic citrullinated peptide antibodies were
      analyzed. The HLA alleles were typed using the DNA-amplified polymerase chain
      reaction with low-resolution hybridization and sequence-specific primers.
      RESULTS: The comparison between the 40 patients without RV and the 17 patients
      with RV showed an increased frequency of HLA-B*14 (Pc = 0.168) and HLA-Cw*08 (Pc
      = 0.084) in patients with RV and an increased frequency of HLA-DRB5*01 (Pc =
      0.048) in patients without RV. CONCLUSION: The HLA-DRB5*01 may confer protection
      against that extra-articular manifestation of RA.

PMID- 22641593
TI  - Diet and nutritional aspects in systemic lupus erythematosus.
AB  - The authors reviewed the influence of nutritional factors on systemic lupus
      erythematosus (SLE) and discussed an alternative treatment option. The
      autoimmunity and inflammatory process of SLE are related to the presence of
      dyslipidemia, obesity, systemic arterial hypertension, and metabolic syndrome,
      which should be properly considered to decrease cardiovascular risk. A diet with
      moderate protein and energy content, but rich in vitamins, minerals (especially
      antioxidants), and mono/polyunsaturated fatty acids can promote a beneficial
      protective effect against tissue damage and suppression of inflammatory activity,
      in addition to helping the treatment of those comorbidities. Diet therapy is a
      promising approach and some recommendations may offer a better quality of life to
      patients with SLE.

PMID- 22641592
TI  - Low prevalence of renal, cardiac, pulmonary, and neurological extra-articular
      clinical manifestations in spondyloarthritis: analysis of the Brazilian Registry
      of Spondyloarthritis.
AB  - OBJECTIVE: To describe the extra-articular manifestations (cardiac, renal,
      pulmonary, and neurological), usually not related to spondyloarthritis (SpA), in
      a large cohort of Brazilian patients. MATERIALS AND METHODS: This retrospective
      study analyzed 1,472 patients diagnosed with SpA and cared for at 29 health care
      centers distributed in the five major geographic regions in the country,
      participating in the Brazilian Registry of Spondyloarthritis (BRS). All patients
      were assessed for the prevalence of major extra-articular manifestations
      (cardiac, renal, pulmonary, and neurological), classified according to the
      diagnosis [ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive
      arthritis (ReA), arthritis associated with inflammatory bowel disease (IBD),
      undifferentiated spondyloarthritis (uSpA), and juvenile SpA], and according to
      the clinical presentation (axial, peripheral, mixed, and enthesitis). RESULTS: Of
      the patients with SpA assessed, 963 had AS, 271 PsA, 49 ReA, 48 arthritis
      associated with IBD, 98 uSpA, and 43 juvenile SpA. Cardiac involvement was
      reported in 44 patients (3.0%), pulmonary involvement in 19 (1.3%), renal
      involvement in 17 (1.2%), and neurological involvement in 13 patients (0.9%).
      Most patients with visceral involvement had AS or PsA, and the mixed (axial +
      peripheral) and/or predominantly axial clinical form. CONCLUSION: Cardiac, renal,
      pulmonary, and neurological extra-articular manifestations are quite infrequent
      in SpA, ranging from 0.9% to 3% in this large Brazilian cohort, and affected
      predominantly patients with AS and PsA.

PMID- 22641594
TI  - Static and dynamic balance in subjects with ankylosing spondylitis: literature
      review.
AB  - To analyze the musculoskeletal changes of individuals with ankylosing spondylitis
      (AS) and their repercussions on postural control, a literature review was carried
      out in the BIREME and EBSCO HOTS databases and Pubmed site with the following
      keywords: "ankylosing spondylitis", "postural balance", and "posture". Articles
      involving human beings, assessing the postural control and balance of individuals
      with AS, written in English or Portuguese and published between 1999 and 2010,
      were selected. Of the total number of articles found, only four met the
      requirements. Of those, three compared the outcomes of patients with AS with data
      obtained from healthy individuals, and one article assessed individuals with AS.
      No article used the same method of postural analysis. To assess balance, Berg
      Balance Scale, Force Plate, and Magnometry were used. The major postural
      deviations found were increased thoracic kyphosis and hip flexion, which lead to
      a forward displacement of the body's center of gravity, with knee flexion and
      ankle plantar flexion as compensation to control balance. Only one author
      reported worsening of functional balance in subjects with AS. All assessment
      methods used were considered capable of measuring balance, and no specific scale
      for patients with AS exists.

PMID- 22641595
TI  - Autoimmune thyroid disease in patients with rheumatic diseases.
AB  - Thyroid function abnormalities and thyroid autoantibodies have been frequently
      described in patients with rheumatologic autoimmune diseases, such as Sjogren's
      syndrome, rheumatoid arthritis, systemic lupus erythematosus and scleroderma.
      Limited data are available regarding the prevalence and clinical characteristics
      of autoimmune thyroiditis in other rheumatologic disorders, such as rheumatic
      fever and juvenile systemic lupus erythematosus. The authors review the
      association of endocrine autoimmune and rheumatic autoimmune diseases, assessing
      various age groups and clinical conditions. The bibliographic survey was
      conducted through the search for scientific articles indexed in the general
      health sciences databases, such as Latin American and Caribbean Health Sciences
      Literature (LILACS), Medline/PubMed, and Scientific Electronic Library Online
      (SciELO). The following descriptors were used: "rheumatic autoimmune diseases and
      autoimmune thyroid diseases"; "thyroid disorders and rheumatic diseases";
      "thyroiditis and rheumatic diseases"; "autoimmune diseases and thyroid"; and
      "pediatric rheumatic diseases and autoimmune thyroid diseases". This study showed
      that, despite contradictory results in the literature, there is a greater
      prevalence of the association between autoimmune thyroid diseases and rheumatic
      diseases, highlighting the possibility of common pathogenic mechanisms among
      them.

PMID- 22641596
TI  - Cocaine-induced midline destruction lesions with positive ANCA test mimicking
      Wegener's granulomatosis.
AB  - Chronic use of cocaine by inhalation may induce midline destructive lesions
      (CIMDL), which can sometimes be difficult to distinguish from the ear, nose and
      throat lesions of Wegener's Granulomatosis (WG). We describe the case of a 43
      year-old female patient admitted with a two-year history of nasal obstruction and
      rhinorrhea. She had been diagnosed with WG for five months, being on prednisone
      and cyclophosphamide. On her physical examination, perforation of her nasal
      septum and palate was observed. Laboratory tests showed elevated acute phase
      proteins and a positive p-ANCA test. ELISA assays anti-proteinase 3 and
      myeloperoxidase were negative. The paranasal sinus computed tomography (CT)
      showed destruction of the nasal septum and palate, in addition to bilateral
      maxillary sinusitis. Chest CT was normal. Nasal mucosal biopsy revealed an
      inflammatory infiltrate, with neither granuloma nor vasculitis. When questioned,
      she admitted being a cocaine user for five years. Medical therapy and cocaine use
      were withdrawn. She has been followed up for six months and no other lesion or
      other organ symptoms occurred. Differential diagnosis in patients with midline
      destructive lesions can be very challenging. Evaluation should include enquiry
      about intranasal use of cocaine. Although ANCA testing does not clearly
      differentiate the ANCA found in some patients with CIMDL from those found in WG
      patients, the localized involvement and the biopsy findings non-characteristic of
      small vessel granulomatous vasculitis should be recognized as features for
      cocaine-induced lesions.

PMID- 22641597
TI  - Thoracic myelopathy due to calcification of the ligamentum flavum with
      hyperproteinorachia and responsive to steroid therapy: case report.
AB  - Calcification and ossification of the ligamentum flavum or of the posterior
      longitudinal ligament are causes of compressive myelopathy, more frequent in the
      lower thoracic levels, and extremely rare in Western populations. Surgical
      decompression is the only therapy, but the disease is usually progressive, and
      its recurrence after surgery is common. Inflammatory mediators might play a role
      in the progression of compressive myelopathy, but, to our knowledge, the
      therapeutic approach involving anti-inflammatory agents has never been tried
      before. We report a case of compressive myelopathy due to calcification of the
      ligamentum flavum, in which hyperproteinorachia and response to steroid therapy
      have been observed. Those data have not been published before and might provide
      new ideas for the disease understanding.

PMID- 22641598
TI  - Cutaneous leishmaniasis in a patient with ankylosing spondylitis using
      adalimumab.
AB  - Leishmaniasis is an anthropozoonosis caused by species of Leishmania and can have
      different clinical presentations, depending on the parasite-host relationship.
      Tumor necrosis factor-alpha (TNF-alpha) is a cytokine essential to infection
      control, especially against intracellular parasites such as Leishmania. Anti-TNF
      alpha strategies have had a marked impact on the treatment of rheumatic diseases,
      but the clinical use of those antagonists has been accompanied by an increased
      report of infections. We report the first case of cutaneous leishmaniasis in a
      patient with ankylosing spondylitis treated with adalimumab and methotrexate in
      Brazil. We believe that, in this case, there was no association between the anti
      TNF-alpha treatment and cutaneous leishmaniasis, because the disease was limited
      to only one ulcer that healed completely after treatment. More studies, however,
      are necessary to better understand the possible relationship between anti-TNF
      alpha agents and leishmaniasis.

PMID- 22641600
TI  - Description of a new method of ovariectomy in female rats.
AB  - Rats are currently the most used laboratory animals to investigate osteoporosis.
      We report an efficient method of ovariectomy and compared this method with the
      two other operative methods of ovariectomy (i.e., midline dorsal skin incision
      and double dorsolateral approach, which are used commonly for inducing
      experimental osteoporosis. Female Wistar rats, 12 weeks old, were divided into
      three groups. Ovariectomy was preceded by a single midline dorsal skin incision,
      3 cm long, in the group A; double dorsolateral incisions, approximately 1 cm
      long, in the group B; and a single ventral transverse incision of 0.4-0.6 cm at
      the middle abdominal region in the group C. Animals in groups A, B, and C had a
      mean weight of 258.12 +/- 0.54 g, 255.78 +/- 0.42 g, and 254.55 +/- 1.69 g,
      respectively. There were significant differences in the duration (in minutes) of
      surgery in the groups B (9.65 +/- 0.86) and C (7.55 +/- 0.11, P < 0.001) when
      compared to the group A (15.52 +/- 0.30) and in the group B (P < 0.01) when
      compared to the group C. Wound healing time (in days) for groups B (9.22 +/-
      0.67) and C (8.01 +/- 0.93) was significantly shorter than that for group A
      (11.58 +/- 1.2, P < 0.001), with the wound healing time for group C being
      slightly shorter than that for group B. The surgery, as conducted in the group C,
      was technically easier, less time consuming and showed less wound healing
      duration.

PMID- 22641599
TI  - Influence of creatine supplementation on bone mass of spontaneously hypertensive
      rats.
AB  - INTRODUCTION: Recent evidence has suggested that creatine supplementation (Cr)
      can increase the bone mineral density (BMD) of the femur in healthy growing rats.
      Nevertheless, studies assessing the efficacy of the Cr supplementation in
      conditions characterized by bone mass loss are scarce. OBJECTIVE: To investigate
      the effect of Cr supplementation on BMD and bone mineral content (BMC) in
      spontaneously hypertensive rats (SHRs), an experimental model of osteoporosis.
      MATERIALS AND METHODS: Sixteen 8-month-old male SHRs were randomly allocated into
      two groups matched by body weight: 1) Pl group: SHRs treated with placebo
      (distilled water; n = 8); and 2) Cr group: SHRs treated with Cr (n = 8). After
      nine weeks of supplementation, the animals were euthanized and their femur and
      spine (L1-L4) were analyzed by use of densitometry (Dual Energy X-Ray
      Absorptiometry). RESULTS: No significant difference was observed between the
      groups regarding either the spine or the total femur measures as follows: spine -
      BMD (Pl = 0.249 +/- 0.003 g/cm2 vs. Cr = 0.249 +/- 0.004 g/cm2; P = 0.95) and BMC
      (Pl = 0.509 +/- 0.150 g vs. Cr = 0.509 +/- 0.017 g; P > 0.99); and total femur -
      BMD (Pl = 0.210 +/- 0.004 g/cm2 vs. Cr = 0.206 +/- 0.004 g/cm2; P > 0.49) and BMC
      (Pl = 0.407 +/- 0.021 g vs. Cr = 0.385 +/- 0.021 g; P > 0.46). CONCLUSION: In
      this study, using the experimental model of osteoporosis, Cr supplementation had
      no effect on bone mass.

PMID- 22641601
TI  - An ultra scale-down approach to assess the impact of the choice of recombinant P.
      pastoris strain on dewatering performance in centrifuges.
AB  - Pichia pastoris is becoming a desirable host in the biopharmaceutical industry
      for therapeutics production. It grows on methanol to high cell densities >=100 g
      DCW/L and secretes foreign proteins at high titers. However, the culture
      conditions to reach high cell densities pose a challenge to the processability by
      primary recovery operations, in particular centrifugation, used for cell removal.
      This work aims to assess the impact of recombinant P. pastoris strain selection
      on centrifugal dewatering. Normally, the choice of P. pastoris recombinant strain
      is based on best target protein expression levels; however, it is unknown whether
      the choice of strain will have an impact on performance of centrifugation
      operation. To achieve this aim, a previously developed laboratory ultra-scale
      down (USD) methodology that successfully predicted centrifugal dewatering of
      pilot-scale disk-type machines, was used in this work. Two recombinant P.
      pastoris strains, namely a X-33 and a glycoengineered Pichia strain, were used to
      perform fermentations secreting different products. The resulting harvested
      fermentation culture properties were analyzed and the dewatering performances of
      a pilot- and a large-scale disk-type centrifuge were evaluated using the USD
      methodology. The choice of P. pastoris strain was found to have a considerable
      impact on dewatering performance, with P. pastoris X-33 strain reaching better
      dewatering levels than the glycoengineered strain. The USD method proved to be a
      useful tool to determine optimal conditions under which the large scale
      centrifuge needed to be operated, reducing the need for repeated pilot-scale runs
      during early stages of process development for therapeutic products.

PMID- 22641602
TI  - Crystal structure of the O intermediate of the Leu93->Ala mutant of
      bacteriorhodopsin.
AB  - The lifetime of the O intermediate of bacteriorhodopsin (BR) is extended by a
      factor of ~250 in the Leu93-to-Ala mutant (BR_L93A). To clarify the structural
      changes occurring in the last stage of the proton pumping cycle of BR, we
      crystallized BR_L93A into a hexagonal P622 crystal. Diffraction data from the
      unphotolyzed state showed that the deletion of three carbon atoms from Leu93 is
      compensated by the insertion of four water molecules in the cytoplasmic vicinity
      of retinal. This insertion of water is suggested to be responsible for the blue
      shifted lambda(max) (540 nm) of the mutant. A long-lived substate of O with a red
      shifted lambda(max) (~565 nm) was trapped when the crystal of BR_L93A was flash
      cooled after illumination with green light. This substate (O(slow)) bears
      considerable similarity to the M intermediate of native BR; that is, it commonly
      shows deformation of helix C and the FG loop, downward orientation of the side
      chain of Arg82, and disruption of the Glu194/Glu204 pair. In O(slow), however,
      the main chain of Lys216 is less distorted and retinal takes on the 13-cis/15-syn
      configuration. Another significant difference is seen in the pH dependence of the
      structure of the proton release group, the pK(a) value of which is suggested to
      be much lower in O(slow) than in M.

PMID- 22641603
TI  - Does obesity modify the association of supplemental folic acid with folate status
      among nonpregnant women of childbearing age in the United States?
AB  - BACKGROUND: Obesity is associated with an increased risk of having a pregnancy
      affected by a neural tube defect (NTD). It is not clear whether the amount of
      folic acid required by obese women to protect against NTDs is the same as that
      for nonobese women. METHODS: We analyzed data from the National Health and
      Nutrition Examination Survey, representative of the noninstitutionalized civilian
      U.S. population, to assess whether body mass index (BMI; normal weight,
      overweight, and obese categories) modified the association between supplemental
      folic acid intake and folate status. We estimated the geometric mean
      concentration among nonpregnant women of childbearing age (15-44 years) during
      the postfortification period of: serum folate (2003-2008); red blood cell (RBC)
      folate (2007-2008); and plasma total homocysteine (tHcy; 2003-2006), adjusted for
      age, race and ethnicity, and total dietary folate expressed as dietary folate
      equivalents for strata of supplement use and BMI. RESULTS: BMI was inversely
      associated with serum folate among women who did not use supplements containing
      folic acid; no differences between women in different BMI categories were
      observed among supplement users. Regardless of supplement use, obese women had
      the highest RBC folate concentrations. There were no differences in tHcy by BMI,
      regardless of supplement use. CONCLUSIONS: These results do not support a
      straightforward modification of the relationship between supplemental folic acid
      intake and folate status by BMI. In this population, BMI may affect the body
      distribution of folate, as reflected by lower serum and higher RBC folate levels
      in obese women who do not use supplements.

PMID- 22641604
TI  - Reversible Ser/Thr SHIP phosphorylation: a new paradigm in phosphoinositide
      signalling?: Targeting of SHIP1/2 phosphatases may be controlled by
      phosphorylation on Ser and Thr residues.
AB  - Phosphoinositide (PI) phosphatases such as the SH2 domain-containing inositol 5
      phosphatases 1/2 (SHIP1 and 2) are important signalling enzymes in human
      physiopathology. SHIP1/2 interact with a large number of immune and growth factor
      receptors. Tyrosine phosphorylation of SHIP1/2 has been considered to be the
      determining regulatory modification. However, here we present a hypothesis, based
      on recent key publications, highlighting the determining role of Ser/Thr
      phosphorylation in regulating several key properties of SHIP1/2. Since a subunit
      of the Ser/Thr phosphatase PP2A has been shown to interact with SHIP2, a putative
      mechanism for reversing SHIP2 Ser/Thr phosphorylation can be anticipated. PI
      phosphatases are potential target molecules in human diseases, particularly, but
      not exclusively, in cancer and diabetes. Therefore, this novel regulatory
      mechanism deserves further attention in the hunt for discovering novel or
      complementary therapeutic strategies. This mechanism may be more broadly involved
      in regulating PI signalling in the case of synaptojanin1 or the phosphatase,
      tensin homolog, deleted on chromosome TEN.

PMID- 22641605
TI  - Temperature and pressure denaturation of chignolin: folding and unfolding
      simulation by multibaric-multithermal molecular dynamics method.
AB  - A multibaric-multithermal molecular dynamics (MD) simulation of a 10-residue
      protein, chignolin, was performed. All-atom model with the Amber parm99SB force
      field was used for the protein and the TIP3P model was used for the explicit
      water molecules. This MD simulation covered wide ranges of temperature between
      260 and 560 K and pressure between 0.1 and 600 MPa and sampled many conformations
      without getting trapped in local-minimum free-energy states. Folding events to
      the native beta-hairpin structure occurred five times and unfolding events were
      observed four times. As the temperature and/or pressure increases, fraction of
      folded chignolin decreases. The partial molar enthalpy change DeltaH and partial
      molar volume change DeltaV of unfolding were calculated as DeltaH = 24.1 +/- 4.9
      kJ/mol and DeltaV = -5.6 +/- 1.5 cm(3)/mol, respectively. These values agree well
      with recent experimental results. Illustrating typical local-minimum free-energy
      conformations, folding and unfolding pathways were revealed. When chignolin
      unfolds from the beta-hairpin structure, only the C terminus or both C and N
      termini open first. It may undergo an alpha-helix or 3(10)-helix structure and
      finally unfolds to the extended structure. Difference of the mechanism between
      temperature denaturation and pressure denaturation is also discussed. Temperature
      denaturation is caused by making the protein transferred to a higher entropy
      state and making it move around more with larger space. The reason for pressure
      denaturation is that water molecules approach the hydrophobic residues, which are
      not well hydrated at the folded state, and some hydrophobic contacts are broken.

PMID- 22641606
TI  - Maternal tea consumption during early pregnancy and the risk of spina bifida.
AB  - Studies have demonstrated that catechin, an antioxidant found in tea, can reduce
      the bioavailability of folate. Because periconceptional folic acid intake has
      been demonstrated to reduce the risk of spina bifida, tea consumption may put
      pregnant women at risk because of its possible antifolate properties. Using data
      collected in the Slone Epidemiology Center Birth Defects Study, we examined
      whether tea consumption during early pregnancy was associated with an increased
      risk of spina bifida. Mothers of 518 spina bifida cases and 6424 controls were
      interviewed within 6 months after delivery about pregnancy events and exposures.
      Data on tea intake were collected during three periods (1976-1988, 1998-2005 and
      2009-2010). Logistic regression models were used to calculate odds ratios (ORs)
      and 95% confidence intervals (CIs), adjusted for study center. Intake of both
      periconceptional food folate and diet and supplemental folic acid were examined
      as a potential effect modifier. For 1976 to 1988, ORs were not elevated for daily
      tea intake. For 1998 and onward, ORs were also close to 1.0, but there was a
      modest increase for those who drank more than 3 cups/day (OR, 1.92; 95% CI, 0.84
      4.38). Among women with total folic acid intake greater than 400 MUg, consumption
      of 3 cups or more of tea per day was associated with an increased risk of spina
      bifida in 1976 to 1988 (OR, 2.04; 95% CI, 0.69-7.66) and in the later periods
      (OR, 3.13; 95% CI, 0.87-11.33). Our data do not support an overall association
      between tea consumption and spina bifida, but there is a suggestion of a possible
      interaction between higher levels of folic acid intake and tea consumption.

PMID- 22641607
TI  - Polyurethane modified with an antithrombin-heparin complex via polyethylene oxide
      linker/spacers: influence of PEO molecular weight and PEO-ATH bond on catalytic
      and direct anticoagulant functions.
AB  - A segmented polyurethane (PU) was modified with polyethylene oxides (PEO) of
      varying molecular weight and end group. The PEO served as linker/spacers to
      immobilize an antithrombin-heparin (ATH) anticoagulant complex on the PU.
      Isocyanate groups were introduced into the PU to enable attachment of either
      "conventional" homo-bifunctional dihydroxy-PEO (PEO-OH surface) or a hetero
      bifunctional amino-carboxy-PEO (PEO-COOH surface). The PEO surfaces were
      functionalized with N-hydroxysuccinimide (NHS) groups using appropriate
      chemistries, and ATH was attached to the distal NHS end of the PEO (PEO-OH-ATH
      and PEO-COOH-ATH surfaces). Water contact angle and fibrinogen adsorption
      measurements showed increased hydrophilicity and reduced fibrinogen adsorption
      from buffer on all PEO surfaces compared to unmodified PU. ATH uptake on NHS
      functionalized PEO was quantified by radiolabeling. Despite the different PEO
      molecular weights and end groups, and NHS-functionalization chemistries, the
      surface densities of ATH were similar. The adsorption of fibrinogen and
      antithrombin (AT) from plasma was measured in a single experiment using dual
      radiolabeling. On PEO-ATH surfaces fibrinogen adsorption was minimal while AT
      adsorption was high showing the selectivity of the heparin moiety of ATH for AT.
      The PEO-COOH-ATH surfaces showed slightly greater AT adsorption than the PEO-OH
      ATH surfaces. Thrombin adsorption on all of the PEO-ATH surfaces was greater than
      on the corresponding PEO surfaces without ATH, and was highest on the PEO-OH-ATH,
      suggesting potential anticoagulant properties for this surface via direct
      thrombin inhibition by the AT portion of ATH.

PMID- 22641609
TI  - A facile polymer templating route toward high-aspect-ratio crystalline titania
      nanostructures.
AB  - High-aspect-ratio rutile and anatase hybrid nanowires are produced via a template
      directed process using a novel cylindrical polyelectrolyte brush template.
      Loading the highly negatively charged 1D templates with pre-synthesized TiO(2)
      nanocrystals, results in the fabrication of soluble crystalline TiO(2) hybrid
      nanowires.

PMID- 22641612
TI  - Analysis of serum and plasma identifies differences in molecular coverage,
      measurement variability, and candidate biomarker selection.
AB  - PURPOSE: To compare the use of serum and plasma in multiplex immunoassay analyses
      of 190 proteins and small molecules, and associated molecular pathways. We also
      tested whether differences between these biofluids can influence the
      identification of potential biomarkers in a preliminary study comparing bipolar
      disorder patients with controls. EXPERIMENTAL DESIGN: Using multiplexed
      immunoassay analyses, we compared the measurement levels and interindividual
      variation of 190 proteins and small molecules between serum and plasma collected
      from 21 healthy individuals. We exemplify how this can impact on the outcome of
      biomarker discovery studies using a case study of 24 patients with bipolar
      disorder. RESULTS: Detection of analytes was similar for serum and plasma,
      although there were marked differences in measurement variability for 29 proteins
      and cortisol. When considering the disease cohort we identified six proteins that
      changed significantly in serum and ten in plasma with an overlap of two proteins.
      CONCLUSIONS AND CLINICAL RELEVANCE: In spite of the similarities of coverage on a
      multiplexed platform for serum and plasma, there were important differences in
      interindividual variability, which can have significant impact on identifications
      made in biomarker studies.

PMID- 22641610
TI  - Application of glycoproteomics for the discovery of biomarkers in lung cancer.
AB  - Lung cancer is the leading cause of cancer-related deaths in the United States.
      Approximately 40-60% of lung cancer patients present with locally advanced or
      metastatic disease at the time of diagnosis. Lung cancer development and
      progression are a multistep process that is characterized by abnormal gene and
      protein expressions ultimately leading to phenotypic change. Glycoproteins have
      long been recognized to play fundamental roles in many physiological and
      pathological processes, particularly in cancer genesis and progression. In order
      to improve the survival rate of lung cancer patients, the discovery of early
      diagnostic and prognostic biomarkers is urgently needed. Herein, we reviewed the
      recent technological developments of glycoproteomics and published data in the
      field of glycoprotein biomarkers in lung cancer, and discussed their utility and
      limitations for the discovery of potential biomarkers in lung cancer. Although
      numerous papers have already acknowledged the importance of the discovery of
      cancer biomarkers, the systemic study of glycoproteins in lung cancer using
      glycoproteomic approaches is still suboptimal. Recent development in the
      glycoproteomics will provide new platforms for identification of potential
      protein biomarkers in lung cancers.

PMID- 22641611
TI  - Precursor ion exclusion for enhanced identification of plasma biomarkers.
AB  - PURPOSE: Our study aims to establish a plasma biomarker analysis workflow, with
      fewer fractionation steps, for enhanced identification of plasma biomarkers by
      precursor ion exclusion (PIE). EXPERIMENTAL DESIGN: Plasma samples were depleted
      for highly abundant proteins, then further fractionated by molecular weight (MW),
      before trypsinization for LTQ-Orbitrap mass analysis. Data-dependent acquisition
      (DDA) was used for baseline analysis. PIE involves the re-injection of samples
      with exclusion of the previously identified peptides. We compared analyses using
      multiple PIE iterations, compared to DDA, for plasma interrogation RESULTS: A
      higher percentage of unique plasma peptides was identified with PIE, compared to
      DDA. The first PIE iteration reveals an increase of 75-112% more peptides than
      the DDA method alone. PIE can interrogate complex plasma samples with the
      percentage of peptides identified successively increasing with even >=4
      iterations. The total number of peptides identified increases rapidly across the
      first three PIE iterations and then continues more slowly up to nine iterations.
      CONCLUSIONS AND CLINICAL RELEVANCE: Iterative injections with PIE resulted in
      many more peptide identifications in plasma samples of varying degrees of
      complexity, compared to re-injections using similar DDA parameters. PIE methods
      may therefore expand our ability to recover plasma peptides for plasma biomarker
      discovery.

PMID- 22641614
TI  - The free-radical theory of ageing--older, wiser and still alive: modelling
      positional effects of the primary targets of ROS reveals new support.
AB  - The continuing viability of the free-radical theory of ageing has been questioned
      following apparently incompatible recent results. We show by modelling positional
      effects of the generation and primary targets of reactive oxygen species that
      many of the apparently negative results are likely to be misleading. We conclude
      that there is instead a need to look more closely at the mechanisms by which free
      radicals contribute to age-related dysfunction in living systems. There also
      needs to be deeper understanding of the dynamics of accumulation and removal of
      the various kinds of molecular damage, in particular mtDNA mutations. Finally,
      the expectation that free-radical damage on its own might cause ageing needs to
      be relinquished in favour of the recognition that the free-radical theory is just
      one of the multiple mechanisms driving the ageing process.

PMID- 22641613
TI  - Application of systems biology principles to protein biomarker discovery: urinary
      exosomal proteome in renal transplantation.
AB  - PURPOSE: In mass spectrometry (MS)-based studies to discover urinary protein
      biomarkers, an important question is how to analyze the data to find the most
      promising potential biomarkers to be advanced to large-scale validation studies.
      Here, we describe a "systems biology-based" approach to address this question.
      EXPERIMENTAL DESIGN: We analyzed large-scale liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) data of urinary exosomes from renal allograft recipients
      with biopsy-proven evidence of immunological rejection or tubular injury (TI). We
      asked whether bioinformatic analysis of urinary exosomal proteins can identify
      biological-process based protein groups that correlate with biopsy findings and
      whether the protein groups fit with general knowledge of the pathophysiological
      mechanisms involved. RESULTS: LC-MS/MS analysis of urinary exosomal proteomes
      identified more than 1000 proteins in each pathologic group. These protein lists
      were analyzed computationally to identify the Biological Process and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) Pathway terms that are significantly
      associated with each pathological group. Among the most informative terms for
      each group were: "sodium ion transport" for TI; "immune response" for all
      rejection; "epithelial cell differentiation" for cell-mediated rejection; and
      "acute inflammatory response" for antibody-mediated rejection. Based on these
      terms, candidate biomarkers were identified using a novel strategy to allow a
      dichotomous classification between different pathologic categories. CONCLUSIONS
      AND CLINICAL RELEVANCE: The terms and candidate biomarkers identified make
      rational connections to pathophysiological mechanisms, suggesting that the
      described bioinformatic approach will be useful in advancing large-scale
      biomarker identification studies toward a validation phase.

PMID- 22641615
TI  - Plant hormone interactions: innovative targets for crop breeding and management.
AB  - Here we highlight how both the root and shoot environment impact on whole plant
      hormone balance, particularly under stresses such as soil drying, and relate
      hormone ratios and relative abundances to processes influencing plant performance
      and yield under both mild and more severe stress. We discuss evidence (i) that
      abscisic acid (ABA) and ethylene act antagonistically on grain-filling rate
      amongst other yield-impacting processes; (ii) that ABA's effectiveness as an
      agent of stomatal closure can be modulated by coincident ethylene or cytokinin
      accumulation; and (iii) that enhanced cytokinin production can increase growth
      and yield by improving foliar stay-green indices under stress, and by improving
      processes that impact grain-filling and number, and that this can be the result
      of altered relative abundances of cytokinin and ABA (and other hormones). We
      describe evidence and novel processes whereby these phenomena are/could be
      amenable to manipulation through genetic and management routes, such that plant
      performance and yield can be improved. We explore the possibility that a range of
      ABA-ethylene and ABA-cytokinin relative abundances could represent targets for
      breeding/managing for yield resilience under a spectrum of stress levels between
      severe and mild, and could circumvent some of the pitfalls so far encountered in
      the massive research effort towards breeding for increases in the complex trait
      of yield.

PMID- 22641616
TI  - Mechanistic investigation of imatinib-induced cardiac toxicity and the
      involvement of c-Abl kinase.
AB  - The Bcr-abl tyrosine kinase inhibitor imatinib mesylate is the frontline therapy
      for chronic myeloid leukemia. Imatinib has been reported to cause congestive
      heart failure and left ventricular contractile dysfunction in patients and
      cardiomyopathy in rodents, findings proposed to be associated with its
      pharmacological activity. To investigate the specific role of Abelson oncogene 1
      (c-Abl) in imatinib-induced cardiac toxicity, we performed targeted gene
      inhibition of c-Abl by RNA interference in neonatal cardiomyocytes (NCMs).
      Suppression of c-Abl did not lead to cytotoxicity or induction of endoplasmic
      reticulum (ER) stress. To further dis associate c-Abl from imatinib-induced
      cardiac toxicity, we designed imatinib structural analogs that do not have
      appreciable c-Abl inhibition in NCMs. The c-Abl inactive analogs induced
      cytotoxicity and ER stress, at similar or greater potencies and magnitudes as
      imatinib. Furthermore, combining c-Abl gene silencing with imatinib and analogs
      treatment did not significantly shift the cytotoxicity dose response curves.
      Imatinib and analogs were shown to accumulate in lysosomes, likely due to their
      physicochemical properties, and disrupt autophagy. The toxicity induced by
      imatinib and analogs can be rescued by bafilomycin A pretreatment, demonstrating
      the involvement of lysosomal accumulation in cardiac toxicity. The results from
      our studies strongly suggest that imatinib induces cardiomyocyte dysfunction
      through disruption of autophagy and induction of ER stress, independent of c-Abl
      inhibition.

PMID- 22641617
TI  - Paternal benzo[a]pyrene exposure affects gene expression in the early developing
      mouse embryo.
AB  - The health of the offspring depends on the genetic constitution of the parental
      germ cells. The paternal genome appears to be important; e.g., de novo mutations
      in some genes seem to arise mostly from the father, whereas epigenetic
      modifications of DNA and histones are frequent in the paternal gonads.
      Environmental contaminants which may affect the integrity of the germ cells
      comprise the polycyclic aromatic hydrocarbon, benzo[a]pyrene (B[a]P). B[a]P has
      received much attention due to its ubiquitous distribution, its carcinogenic and
      mutagenic potential, and also effects on reproduction. We conducted an in vitro
      fertilization (IVF) experiment using sperm cells from B[a]P-exposed male mice to
      study effects of paternal B[a]P exposure on early gene expression in the
      developing mouse embryo. Male mice were exposed to a single acute dose of B[a]P
      (150 mg/kg, ip) 4 days prior to isolation of cauda sperm, followed by IVF of
      oocytes from unexposed superovulated mice. Gene expression in fertilized
      zygotes/embryos was determined using reverse transcription-qPCR at the 1-, 2-, 4
      , 8-, and blastocyst cell stages of embryo development. We found that paternal
      B[a]P exposure altered the expression of numerous genes in the developing embryo
      especially at the blastocyst stage. Some genes were also affected at earlier
      developmental stages. Embryonic gene expression studies seem useful to identify
      perturbations of signaling pathways resulting from exposure to contaminants, and
      can be used to address mechanisms of paternal effects on embryo development.

PMID- 22641618
TI  - In silico identification of potential cholestasis-inducing agents via modeling of
      Na(+)-dependent taurocholate cotransporting polypeptide substrate specificity.
AB  - Na(+)-dependent taurocholate cotransporting polypeptide (NTCP, SLC10A1) is the
      main transporter facilitating the hepatic uptake of bile acids from the
      circulation. Consequently, the interaction of xenobiotics, including therapeutic
      drugs, with the bile acid binding pocket of NTCP could lead to impairment of
      hepatic bile acid uptake. We pursued a 3D-pharmacophore approach to model the
      NTCP substrate and inhibitor specificity and investigated whether it is possible
      to identify compounds with intrinsic NTCP inhibitory properties. Based on known
      endogenous NTCP substrates, a 3D-pharmacophore model was built, which was
      subsequently used to screen two virtual libraries together containing the
      structures of 10 million compounds. Studies with Chinese hamster ovary cells
      overexpressing human NTCP, human hepatocytes, ex vivo perfused rat livers, and
      bile duct-cannulated rats were conducted to validate the activity of the virtual
      screening hits. Modeling yielded a 3D-pharmacophore, consisting of two hydrogen
      bond acceptors and three hydrophobic features. Six out of 10 structurally diverse
      compounds selected in the first virtual screening procedure significantly
      inhibited taurocholate uptake in the NTCP overexpressing cells. For the most
      potent inhibitor identified, an anthraquinone derivative, this finding was
      confirmed in human hepatocytes and perfused rat livers. Subsequent structure and
      activity relationship studies with analogs of this derivative indicated that an
      appropriate distance between hydrogen bond acceptor features and presence of one
      or two negative charges appear critical for a successful NTCP interaction. In
      conclusion, pharmacophore modeling was successfully used to identify compounds
      that inhibit NTCP. Our approach represents an important first step toward the in
      silico flagging of potential cholestasis-inducing molecules.

PMID- 22641619
TI  - Effects of developmental lead exposure on the hippocampal transcriptome:
      influences of sex, developmental period, and lead exposure level.
AB  - Developmental lead (Pb) exposure has profound effects on cognition and behavior.
      Much is known about effects of Pb on hippocampal-mediated behaviors, but little
      is known about the molecular consequences of Pb exposure and the influences of
      developmental timing of exposure, level of exposure, and sex as effect modifiers
      of Pb exposure on the brain. The aim of this study was to examine the effects of
      different levels of Pb exposure (250 and 750 ppm Pb acetate) during perinatal
      (gestation/lactation) and postnatal (through postnatal day 45) periods on the
      hippocampal transcriptome in male and female Long Evans rats. Total RNA was
      extracted from hippocampus from four animals per experimental condition. RNA was
      hybridized to Affymetrix Rat Gene RNA Arrays using standard methods. Pb exposure
      per se influenced the expression of 717 transcripts (328 unique annotated genes),
      with many influenced in a sex-independent manner. Significant differences in gene
      expression patterns were also influenced by timing and level of exposure, with
      generally larger effects at the lower level of exposure across all groups.
      Statistically enriched biological functions included ion binding, regulation of
      RNA metabolic processes, and positive regulation of macromolecule biosynthetic
      processes. Processes of regulation of transcription and regulation of gene
      expression were preferentially enriched in males, regardless of timing or amount
      of Pb exposure. The effect on transcription factors and the diverse pathways or
      networks affected by Pb suggest a substantial effect of developmental Pb exposure
      on plasticity and adaptability, with these effects significantly modified by sex,
      developmental window of exposure, and level of Pb exposure.

PMID- 22641622
TI  - Hospital volume determines favourable outcome: probably also in internal
      medicine.

PMID- 22641620
TI  - Amelioration of metal-induced toxicity in Caenorhabditis elegans: utility of
      chelating agents in the bioremediation of metals.
AB  - The presence of toxic amounts of transition metals in the environment may
      originate from a range of human activities and natural processes. One method for
      the removal of toxic levels of metals is through chelation by small molecules.
      However, chelation is not synonymous with detoxification and may not affect the
      bioavailability of the metal. To test the bioavailability of chelated metals in
      vivo, the effects of several metal/chelator combinations were tested in the
      environmentally relevant organism Caenorhabditis elegans. The effect of metal
      exposure on nematode growth was used to determine the toxicity of cadmium,
      copper, nickel, and zinc. The restoration of growth to levels observed in
      nonexposed nematodes was used to determine the protective effects of the
      polydentate chelators: acetohydroxamic acid (AHA), cyclam, cysteine, calcium
      EDTA, desferrioxamine B, 1,2-dimethyl,3-hydroxy,4-pyridinone, and histidine.
      Cadmium toxicity was removed only by EDTA; copper toxicity was removed by all of
      the chelators except AHA; nickel toxicity was removed by cyclam, EDTA, and
      histidine; and zinc toxicity was removed by only EDTA. These results demonstrate
      the utility of polydentate chelators in the remediation of metal-contaminated
      systems. They also demonstrate that although the application of a chelator to
      metal contaminants may be effective, binding alone cannot be used to predict the
      level of remediation. Remediation depends on a number of factors, including metal
      complex speciation in the environment.

PMID- 22641623
TI  - Myeloproliferative neoplasia: a review of clinical criteria and treatment.
AB  - Essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis
      (PMF) belong to the group of Philadelphia chromosome-negative myeloproliferative
      neoplasia (Ph- MPN). MPNs are clonal bone marrow stem cell disorders
      characterised by a proliferation of one or more of the myeloid, erythroid or
      megakaryocytic cell lines. Due to the different affected cell lines, MPNs show
      typical clinical and histological features. In 2005, a mutation in the JAK2 gene
      was discovered which generated more insight into the pathogenetic working
      mechanism of MPNs. However, the treatment of MPN patients is still mainly only
      palliative, although progress in reducing the symptoms of MPN patients has been
      made. This review will give a general overview of MPN patients for internal
      medicine physicians.

PMID- 22641621
TI  - Arsenic exposure inhibits myogenesis and neurogenesis in P19 stem cells through
      repression of the beta-catenin signaling pathway.
AB  - Epidemiological studies have correlated embryonic arsenic exposure with adverse
      developmental outcomes such as stillbirths, neonatal mortality, and low birth
      weight. Additionally, arsenic exposure reduces neuronal cell migration and
      maturation, and reduces skeletal muscle cell formation, alters muscle fiber
      subtype, and changes locomotor activity. This study used P19 mouse embryonic stem
      cells to examine whether arsenic exposure could alter their differentiation into
      skeletal muscles and neurons. When P19 cells were exposed to 0.1, 0.5, or 1.0 MUM
      sodium arsenite, embryoid body (EB) formation was not altered. However, arsenic
      suppressed their differentiation into muscles and neurons, as evidenced by
      morphological changes accompanied by a significant reduction in myosin heavy
      chain and Tuj1 expression. Real-time PCR, immunofluorescence, and immunoblotting
      were used to confirm that the altered differentiation was due to the repression
      of muscle- and neuron-specific transcription factors such as Pax3, Myf5, MyoD,
      myogenin, neurogenin 1, neurogenin 2, and NeuroD in the arsenite-exposed cells.
      The reductions in transcription factors expression appear to be caused by
      repressed Wnt/beta-catenin signaling pathways in early embryogenesis, as
      evidenced by decreased beta-catenin expression in the arsenic-exposed EBs on
      differentiation days 2 and 5. Interestingly, the expression of Nanog, a
      transcription factor that maintains the pluripotency of stem cells, was increased
      after arsenite exposure, indicating that arsenite inhibits their differentiation
      but not proliferation. This study demonstrates that arsenic can perturb the
      embryonic differentiation process by repressing the Wnt/beta-catenin signaling
      pathway. More importantly, this study may provide insight into how arsenic
      exposure affects skeletal and neuronal differentiation during embryogenesis.

PMID- 22641624
TI  - Walled-off pancreatic necrosis.
AB  - Acute severe pancreatitits may be complicated by the development of 'walled-off
      pancreatic necrosis' (WOPN), which is characterised by a mixture of solid
      components and fluids on imaging studies as a consequence of organised pancreatic
      tissue necrosis. We present here an overview of the definition, clinical
      features, and diagnostic and therapeutic management of this clinical condition,
      which is mostly based on consensus as adequate clinical trials are lacking.

PMID- 22641625
TI  - BK virus infection in transplant recipients: clinical manifestations, treatment
      options and the immune response.
AB  - Polyomavirus BK (BKV) is ubiquitously present amongst the general population
      establishing a latent, seemingly asymptomatic infection in immunocompetent
      individuals. In transplant recipients, however, BKV reactivation is common and
      can lead to distinctive pathological entities in different patient groups: in
      renal transplant (RT) recipients, it is associated with nephropathy (BKVN) and
      ureteral stenosis, and in haematopoietic stem cell transplant (HSCT) recipients
      with haemorrhagic cystitis (HC). Furthermore, BKV employs several potentially
      oncogenic mechanisms to promote its replication in cells and has been
      inconsistently linked to the development of malignancies. BKVN is currently a
      major cause of allograft failure in RT recipients. HC causes prolonged hospital
      stay and increased mortality in HSCT recipients. Despite its discovery more than
      40 years ago, few advances have been made with regard to therapeutic strategies.
      Current therapies aim to restore the impaired immune response, e.g. by lowering
      immunosuppressive agents in RT recipients. However, this is a double-edged sword
      since it also increases the chance of rejection. Therefore, more specific and
      effective treatment strategies are urgently needed. Here, we will review the
      current knowledge on the structure and lifecycle of BKV, characteristics of the
      BKV-specific immune response, its clinical manifestations and the strengths and
      limitations of available treatments Polyomavirus BK (BKV) is ubiquitously present
      amongst the general population establishing a latent, seemingly asymptomatic
      infection in immunocompetent individuals. In transplant recipients, however, BKV
      reactivation is common and can lead to distinctive pathological entities in
      different patient groups: in renal transplant (RT) recipients, it is associated
      with nephropathy (BKVN) and ureteral stenosis, and in haematopoietic stem cell
      transplant (HSCT) recipients with haemorrhagic cystitis (HC). Furthermore, BKV
      employs several potentially oncogenic mechanisms to promote its replication in
      cells and has been inconsistently linked to the development of malignancies. BKVN
      is currently a major cause of allograft failure in RT recipients. HC causes
      prolonged hospital stay and increased mortality in HSCT recipients. Despite its
      discovery more than 40 years ago, few advances have been made with regard to
      therapeutic strategies. Current therapies aim to restore the impaired immune
      response, e.g. by lowering immunosuppressive agents in RT recipients. However,
      this is a double-edged sword since it also increases the chance of rejection.
      Therefore, more specific and effective treatment strategies are urgently needed.
      Here, we will review the current knowledge on the structure and lifecycle of BKV,
      characteristics of the BKV-specific immune response, its clinical manifestations
      and the strengths and limitations of available treatments methods.

PMID- 22641626
TI  - Low complication rates in the use of port-a-caths in oncology patients.
AB  - BACKGROUND: Port-a-caths (PACs) represent an important component of the care of
      cancer patients, in particular for administration of chemotherapy. We sought to
      analyse the longevity and complications of PACs in cancer patients in a large
      community hospital. METHODS: We retrospectively analysed the indications,
      duration of use, complications and reasons for removal of PACs in cancer patients
      treated in our centre from January 2005 to December 2010, and compared these with
      findings in patients who received a PAC in the same period for reasons not
      related to cancer. RESULTS: During the study period 152 cancer patients received
      a total of 170 PACs; in the same period, 21 patients received a total of 35 PACs
      for reasons unrelated to cancer. The total analysis comprised 70,919 days of PAC
      use. Most cancer patients had a solid tumour (97%). PACs were removed because of
      a complication in 25 cases in cancer patients (14.7%) vs 15 cases in non-cancer
      patients (42.9%, p.

PMID- 22641627
TI  - An unexpected cause of multiple intra-abdominal abscesses in an HIV-positive
      patient.
AB  - This case report describes a female HIV-positive patient diagnosed with pelvic
      actinomycosis using 16S rRNA gene sequence analysis. Actinomycosis is notoriously
      difficult to diagnose by microbiological culture. 16S rRNA gene sequence analysis
      allows rapid definitive diagnosis of actinomycosis and is potentially of great
      value in a clinical setting. This is the first report of pelvic actinomycosis in
      an HIV-1 infected patient.

PMID- 22641629
TI  - An unusual cause of ascites. Mucoid adenocarcinoma with signet cell
      differentiation.

PMID- 22641628
TI  - An unexpected cause of chest pain. Penetrating aortic ulcer.

PMID- 22641630
TI  - A man with painless scrotal swelling. Scrotal emphysema (pneumoscrotum).

PMID- 22641631
TI  - A patient with haemorrhagic bullae. Varicella zoster virus (VZV).

PMID- 22641632
TI  - Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis.
AB  - Proliferative lupus nephritis is a strong predictor of morbidity and mortality in
      patients with systemic lupus erythematosus. Despite improvements in the
      management of lupus nephritis, a significant number of the patients do not
      respond to immunosuppressive therapy and progress to end-stage renal failure. In
      order to optimise the diagnostic strategy and treatment of patients with
      proliferative lupus nephritis, guidelines are needed. In this review, the Dutch
      Working Party on Systemic Lupus Erythematosus provides recommendations regarding
      four important areas in patients with proliferative lupus nephritis: I)
      indications for a first renal biopsy, II ) definitions of treatment response, III
      ) selection of treatment options, and IV) indications for a repeat biopsy.

PMID- 22641633
TI  - Perspectives on: SGP symposium on mitochondrial physiology and medicine:
      mitochondria take center stage.

PMID- 22641634
TI  - Perspectives on: SGP symposium on mitochondrial physiology and medicine:
      mitochondrial proteome design: from molecular identity to pathophysiological
      regulation.

PMID- 22641635
TI  - Perspectives on: SGP symposium on mitochondrial physiology and medicine:
      metabolic homeostasis of the heart.

PMID- 22641636
TI  - Perspectives on: SGP symposium on mitochondrial physiology and medicine: the
      renaissance of mitochondrial pH.

PMID- 22641637
TI  - Perspectives on: SGP symposium on mitochondrial physiology and medicine:
      mitochondrial superoxide flashes: from discovery to new controversies.

PMID- 22641638
TI  - Perspectives on: SGP symposium on mitochondrial physiology and medicine:
      molecular identities of mitochondrial Ca2+ influx mechanism: updated passwords
      for accessing mitochondrial Ca2+-linked health and disease.

PMID- 22641639
TI  - Perspectives on: SGP symposium on mitochondrial physiology and medicine: the
      pathophysiology of LETM1.

PMID- 22641640
TI  - Perspectives on: SGP symposium on mitochondrial physiology and medicine: what
      comes first, misshape or dysfunction? The view from metabolic excess.

PMID- 22641641
TI  - Dynamics of matrix-free Ca2+ in cardiac mitochondria: two components of Ca2+
      uptake and role of phosphate buffering.
AB  - Mitochondrial Ca(2+) uptake is thought to provide an important signal to increase
      energy production to meet demand but, in excess, can also trigger cell death. The
      mechanisms defining the relationship between total Ca(2+) uptake, changes in
      mitochondrial matrix free Ca(2+), and the activation of the mitochondrial
      permeability transition pore (PTP) are not well understood. We quantitatively
      measure changes in [Ca(2+)](out) and [Ca(2+)](mito) during Ca(2+) uptake in
      isolated cardiac mitochondria and identify two components of Ca(2+) influx.
      [Ca(2+)](mito) recordings revealed that the first, MCU(mode1), required at least
      1 uM Ru360 to be completely inhibited, and responded to small Ca(2+) additions in
      the range of 0.1 to 2 uM with rapid and large changes in [Ca(2+)](mito). The
      second component, MCU(mode2), was blocked by 100 nM Ru360 and was responsible for
      the bulk of total Ca(2+) uptake for large Ca(2+) additions in the range of 2 to
      10 uM; however, it had little effect on steady-state [Ca(2+)](mito). MCU(mode1)
      mediates changes in [Ca(2+)](mito) of 10s of MUM, even in the presence of 100 nM
      Ru360, indicating that there is a finite degree of Ca(2+) buffering in the matrix
      associated with this pathway. In contrast, the much higher Ca(2+) loads evoked by
      MCU(mode2) activate a secondary dynamic Ca(2+) buffering system consistent with
      calcium-phosphate complex formation. Increasing P(i) potentiated [Ca(2+)](mito)
      increases via MCU(mode1) but suppressed [Ca(2+)](mito) changes via MCU(mode2).
      The results suggest that the role of MCU(mode1) might be to modulate oxidative
      phosphorylation in response to intracellular Ca(2+) signaling, whereas MCU(mode2)
      and the dynamic high-capacity Ca(2+) buffering system constitute a Ca(2+) sink
      function. Interestingly, the trigger for PTP activation is unlikely to be
      [Ca(2+)](mito) itself but rather a downstream byproduct of total mitochondrial
      Ca(2+) loading.

PMID- 22641643
TI  - Local anesthetic inhibition of a bacterial sodium channel.
AB  - Recent structural breakthroughs with the voltage-gated sodium channel from
      Arcobacter butzleri suggest that such bacterial channels may provide a structural
      platform to advance the understanding of eukaryotic sodium channel gating and
      pharmacology. We therefore set out to determine whether compounds known to
      interact with eukaryotic Na(V)s could also inhibit the bacterial channel from
      Bacillus halodurans and NaChBac and whether they did so through similar
      mechanisms as in their eukaryotic homologues. The data show that the archetypal
      local anesthetic (LA) lidocaine inhibits resting NaChBac channels with a
      dissociation constant (K(d)) of 260 uM, and channels displayed a left-shifted
      steady-state inactivation gating relationship in the presence of the drug.
      Extracellular application of QX-314 to expressed NaChBac channels had no effect
      on sodium current, whereas internal exposure via injection of a bolus of the
      quaternary derivative rapidly reduced sodium conductance, consistent with a
      hydrophilic cytoplasmic access pathway to an internal binding site. However, the
      neutral derivative benzocaine applied externally inhibited NaChBac channels,
      suggesting that hydrophobic pathways can also provide drug access to inhibit
      channels. Alternatively, ranolazine, a putative preopen state blocker of
      eukaryotic Na(V)s, displayed a K(d) of 60 uM and left-shifted the NaChBac
      activation-voltage relationship. In each case, block enhanced entry into the
      inactivated state of the channel, an effect that is well described by a simple
      kinetic scheme. The data suggest that although significant differences exist, LA
      block of eukaryotic Na(V)s also occurs in bacterial sodium channels and that
      NaChBac shares pharmacological homology to the resting state of vertebrate Na(V)
      homologues.

PMID- 22641642
TI  - Low aqueous solubility of 11-cis-retinal limits the rate of pigment formation and
      dark adaptation in salamander rods.
AB  - We report experiments designed to test the hypothesis that the aqueous solubility
      of 11-cis-retinoids plays a significant role in the rate of visual pigment
      regeneration. Therefore, we have compared the aqueous solubility and the
      partition coefficients in photoreceptor membranes of native 11-cis-retinal and an
      analogue retinoid, 11-cis 4-OH retinal, which has a significantly higher
      solubility in aqueous medium. We have then correlated these parameters with the
      rates of pigment regeneration and sensitivity recovery that are observed when
      bleached intact salamander rod photoreceptors are treated with physiological
      solutions containing these retinoids. We report the following results: (a) 11-cis
      4-OH retinal is more soluble in aqueous buffer than 11-cis-retinal. (b) Both 11
      cis-retinal and 11-cis 4-OH retinal have extremely high partition coefficients in
      photoreceptor membranes, though the partition coefficient of 11-cis-retinal is
      roughly 50-fold greater than that of 11-cis 4-OH retinal. (c) Intact bleached
      isolated rods treated with solutions containing equimolar amounts of 11-cis
      retinal or 11-cis 4-OH retinal form functional visual pigments that promote full
      recovery of dark current, sensitivity, and response kinetics. However, rods
      treated with 11-cis 4-OH retinal regenerated on average fivefold faster than rods
      treated with 11-cis-retinal. (d) Pigment regeneration from recombinant and wild
      type opsin in solution is slower when treated with 11-cis 4-OH retinal than with
      11-cis-retinal. Based on these observations, we propose a model in which aqueous
      solubility of cis-retinoids within the photoreceptor cytosol can place a limit on
      the rate of visual pigment regeneration in vertebrate photoreceptors. We conclude
      that the cytosolic gap between the plasma membrane and the disk membranes
      presents a bottleneck for retinoid flux that results in slowed pigment
      regeneration and dark adaptation in rod photoreceptors.

PMID- 22641644
TI  - Low-dose radiation exposure and carcinogenesis.
AB  - Absorption of energy from ionizing radiation by the genetic material in the cell
      leads to damage to DNA, which in turn leads to cell death, chromosome aberrations
      and gene mutations. While early or deterministic effects result from organ and
      tissue damage caused by cell killing, latter two are considered to be involved in
      the initial events that lead to the development of cancer. Epidemiological
      studies have demonstrated the dose-response relationships for cancer induction
      and quantitative evaluations of cancer risk following exposure to moderate to
      high doses of low-linear energy transfer radiation. A linear, no-threshold model
      has been applied to assessment of the risks resulting from exposure to moderate
      and high doses of ionizing radiation; however, a statistically significant
      increase has hardly been described for radiation doses below 100 mSv. This review
      summarizes our current knowledge of the physical and biological features of low
      dose radiation and discusses the possibilities of induction of cancer by low-dose
      radiation.

PMID- 22641645
TI  - Metastasis at the colostomy site: a rare case report.
AB  - Metastasis at the colostomy site is rare. Most reported patients with such
      metastases undergo abdominoperineal resection and this kind of metastases
      happened after a longer period post-cancer surgery. In our patient, because it
      happened during a short interval between rectal cancer surgery and stoma closure,
      colostomy site metastasis probably occurred owing to ablative cancer cell reflux
      and seeding from the obstruction during decompressive colostomy rather than
      local, lymphatic or haematogenous spread. Meticulous histologic analyses to rule
      out undetected, concomitant polyps and metachronous cancer are very important for
      patients with obstructive colorectal cancer who undergo decompressive colostomy.
      The potential risk of colostomy site metastasis during staged surgery for
      obstructive colorectal cancer remains uncertain; however, the result from this
      case report raises the question of such a risk for further studies in a greater
      number of patients.

PMID- 22641646
TI  - Bicc1 links the regulation of cAMP signaling in polycystic kidneys to microRNA
      induced gene silencing.
AB  - Genetic defects in autosomal-dominant polycystic kidney disease (ADPKD) promote
      cystic growth of renal tubules, at least in part by stimulating the accumulation
      of cAMP. How renal cAMP levels are regulated is incompletely understood. We show
      that cAMP and the expression of its synthetic enzyme adenylate cyclase-6 (AC6)
      are up-regulated in cystic kidneys of Bicc1(-)(/-) knockout mice. Bicc1, a
      protein comprising three K homology (KH) domains and a sterile alpha motif (SAM),
      is expressed in proximal tubules. The KH domains independently bind AC6 mRNA and
      recruit the miR-125a from Dicer, whereas the SAM domain enables silencing by
      Argonaute and TNRC6A/GW182. Bicc1 similarly induces silencing of the protein
      kinase inhibitor PKIalpha by miR-27a. Thus, Bicc1 is needed on these target mRNAs
      for silencing by specific miRNAs. The repression of AC6 by Bicc1 might explain
      why cysts in ADPKD patients preferentially arise from distal tubules.

PMID- 22641647
TI  - Srs2 possesses a non-canonical PIP box in front of its SBM for precise
      recognition of SUMOylated PCNA.

PMID- 22641648
TI  - Persistent hemolysis in a patient with pancreatitis.

PMID- 22641649
TI  - Commentary.

PMID- 22641650
TI  - Commentary.

PMID- 22641651
TI  - Cookie lover's crash.

PMID- 22641656
TI  - Biological response modifiers used in cancer biotherapy.
AB  - Biotherapy is a form of treatment that uses the natural immune system to protect
      the body against infection, cancer, and other diseases, and can fortify the body
      against some side-effects of other treatments. Biotherapy employs substances
      called biological response modifiers (BRMs), which include vaccines, monoclonal
      antibodies, cytokines, and adjuvants. BRMs are used alone or in combination with
      each other. Several BRMs are widely accepted in the treatment of certain types of
      cancer, while others are being tried in research studies. Side-effects of
      biotherapy vary among agents and patients. However, these side-effects usually
      disappear after the end of treatment.

PMID- 22641657
TI  - Boron tracedrugs challenge for neutron dynamic therapy.
AB  - In this short review we describe our innovative boron tracedrugs and drugs for
      neutron dynamic therapy (NDT), as a newly emerging challenge beyond conventional
      drug treatments.

PMID- 22641658
TI  - Cancer immunotherapy using NKG2D and DNAM-1 systems.
AB  - Although tumor antigen-specific immunotherapy, such as dendritic cell vaccine,
      has recently emerged as a promising clinical approach, one limitation of tumor
      antigen- and T-cell receptor (TcR)-specific immunotherapy is antigen-specific
      inhibition by antigen-specific regulatory T-cell and myeloid suppressor cells.
      Therefore, immunotherapy using a TcR-independent mechanism may be an alternative
      immunotherapeutic strategy. NKG2D (natural killer, group 2, member D) and DNAX
      accessory molecule-1 (DNAM-1) are both activated receptors that are strongly
      expressed on T-cells, gammadeltaT-cells, and NK cells. Therefore, the expression
      of ligands for NKG2D and DNAM-1 on tumor cells plays an important role in tumor
      opsonization by immune effector cell targeting. Various modulatory methods for up
      regulating NKG2D and DNAM-1-ligands have been reported, and included
      chemotherapeutic agents and hyperthermia. Although there are many obstacles to
      the utilization of NKG2D and DNAM-1 for cancer therapy, combined treatments using
      immune cell therapy and chemotherapy that take advantage of NKG2D and DNAM-1 may
      be an ideal approach.

PMID- 22641659
TI  - Combining cetuximab with killer lymphocytes synergistically inhibits human
      cholangiocarcinoma cells in vitro.
AB  - AIM: We explored the possibility of combining adoptive immunotherapy with
      cytokine-activated killer (CAK) cells and the epidermal growth factor receptor
      monoclonal antibody, cetuximab, as a treatment for cholangiocarcinoma. MATERIALS
      AND METHODS: CAK cells were cultured with a high-dose of interleukin-2 and anti
      CD3 monoclonal antibodies. This cell population contained both activated
      CD16+/CD56+ (NK) cells and CD3+/NKG2D(high+) T-cells. The effect of CAK cells and
      cetuximab, alone and in combination, on the viability of human cholangiocarcinoma
      cells was evaluated. RESULTS: Culture of CAK cells alone, but not cetuximab
      alone, exhibited modest cytotoxicity toward cholangiocarcinoma cells. However,
      combining CAK cells with cetuximab significantly enhanced cytotoxicity. This
      enhancement was inhibited by the addition of excess human immunoglobulins,
      suggesting that antibody-dependent cytotoxicity, mediated by activated NK cells
      in the CAK cell culture was involved in this mechanism. CONCLUSION: Cetuximab may
      be used to enhance CAK cell therapeutic activity in patients with
      cholangiocarcinoma, by potentiating antibody-dependent cellular cytotoxicity.

PMID- 22641660
TI  - Reconsideration of macrophage and dendritic cell classification.
AB  - It is well known that the activation of innate immune cells, especially antigen
      presenting cells such as macrophages and dendritic cells, can ameliorate or
      exacerbate various diseases, including cancer. Currently, the macrophages and
      dendritic cells are categorized into several groups by their cell surface and
      intracellular molecules. However, the detailed classification of the differences
      between macrophages and dendritic cells has still not been established. Here, we
      summarized and reviewed the previous studies on the classification of macrophages
      and dendritic cells. In addition, the previous classification of monocytes,
      macrophages and dendritic cells is discussed based on our findings of macrophage
      activation, which has both conventional and plasmacytoid dendritic cell
      phenotype.

PMID- 22641661
TI  - Phase I trial of Wilms' Tumor 1 (WT1) peptide vaccine with GM-CSF or CpG in
      patients with solid malignancy.
AB  - BACKGROUND: The aim of this study was to investigate the safety and efficacy of
      combinatorial use of granulocyte-macrophage colony-stimulating factor (GM-CSF)
      and CpG oligodeoxynucleotides (CpG-ODN) as immunoenhancement adjuvants in Wilms'
      Tumor 1 (WT1) vaccine therapy for patients with solid malignancy. PATIENTS AND
      METHODS: The patients were placed into treatment groups as follows: WT1 peptide
      alone, WT1 peptide with GM-CSF (100 MUg) and WT1 peptide with CpG-ODN (100 MUg).
      HLA-A *2402 or *0201/*0206-restricted, WT1 peptide emulsified with Montanide
      ISA51 was injected intradermally every week for eight weeks. Toxicities were
      evaluated according to the National Cancer Institute Common Terminology Criteria
      for Adverse Events ver. 3.0. Tumor size, which was measured by computed
      tomography, was determined every four weeks. The responses were analyzed
      according to Response Evaluation Criteria in Solid Tumors. RESULTS: The protocol
      was well tolerated; only local erythema occurred at the WT1 vaccine injection
      site. The disease control rate of the groups treated with WT1 peptide alone
      (n=10), with combinatorial use of GM-CSF (n=8) and with combinatorial use of CpG
      ODN (n=10), in the initial two months was 20%, 25% and 60%, respectively.
      CONCLUSION: Addition of GM-CSF or CpG-ODN to the WT1 peptide vaccine for patients
      with solid malignancy was safe and improved the effectiveness of clinical
      response.

PMID- 22641662
TI  - KRAS up-regulates the expression of miR-181a, miR-200c and miR-210 in a three
      dimensional-specific manner in DLD-1 colorectal cancer cells.
AB  - BACKGROUND: We previously found that oncogenic KRAS induces increased expression
      of microRNAs (miRNAs), such as miR-200c and miR-221/222, in human colorectal
      cancer (CRC) HCT116 cells in a three-dimensional (3D)-specific manner, however,
      the regulation of miRNA expression through oncogenic KRAS in other types of CRC
      remains unclear. MATERIALS AND METHODS: The differential expression of 94 cancer
      related miRNAs was examined in DLD-1 and DKO-4 cells (DLD-1 cells with a
      disrupted oncogenic KRAS) in 3D cultures. RESULTS: Increased miR-15b, miR-16, miR
      23a, miR-24, miR-103 and miR-222 expression was observed in 3D and in 2D
      cultures. Of note, increased miR-181a, miR-200c and miR-210 expression was only
      observed in 3D cultures. Furthermore, miR-181a and miR-210 were significantly
      overexpressed in DLD-1 cells in 3D culture compared with those in HCT116 cells,
      and were significantly overexpressed in human CRC specimens. CONCLUSION:
      Oncogenic KRAS regulates 3D-specific miRNAs that are possibly associated with CRC
      development in vivo.

PMID- 22641663
TI  - Expression of dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase
      and thymidylate synthase in patients with primary colorectal cancer, and
      associations with site of first metastasis.
AB  - AIM: The activity of the widely used anticancer drug 5-fluorouracil (5-FU) is
      determined by the presence of several enzymes, including dihydropyrimidine
      dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), and thymidylate
      synthase (TS). This study compared the expression levels of these enzymes between
      primary colorectal cancer with and without distant metastases, and examined
      whether these expression patterns are associated with hematogenous metastasis.
      MATERIALS AND METHODS: Among 40 patients with colorectal cancer, 20 had no
      metastasis and 20 had distant metastasis. Strong expression on
      immunohistochemistry was classified as positive, while weak, moderate or no
      expression was classified as negative. RESULTS: Positive expressions of DPD, OPRT
      and TS in primary colorectal cancer tissue were seen in 47.5%, 75% and 20%,
      respectively. However, no relationships were observed among the expressions of
      DPD, OPRT and TS. Expressions of OPRT (p=0.029) and TS (p=0.017) in primary
      tissues were significantly associated with hematogenous metastasis. Patterns of
      the expression of the three enzymes varied, and were classified in six ways. A
      tendency was seen for primary colorectal cancer with DPD-high expression to have
      liver metastasis and for that with DPD-low expression, to have lung metastasis.
      CONCLUSION: High expression levels of OPRT and TS in colorectal cancer appear to
      be significantly involved in metastasis after curative surgery. The organs in
      which metastases arise may be controlled by the expression of DPD.

PMID- 22641664
TI  - Endometrial cancer stem cells: a new target for cancer therapy.
AB  - Adult stem cells have recently been identified in several types of mature tissue
      and it has also been suggested that stem-like cells exist in cancerous tissues.
      In this regard, stem-like cell subpopulations, referred to as side-population
      (SP) cells, have been identified in several tissue and tumor types, based on
      their ability to remove intracellular Hoechst 33342, a fluorescent dye. We have
      isolated and characterized SP cells from normal human endometrium and an
      endometrial cancer cell line. Endometrial SP cells can function as progenitor
      cells. Endometrial cancer SP cells possess the following characteristics: i)
      reduced expression levels of differentiation markers, ii) long-term repopulating
      properties, iii) self-renewal capacity, iv) enhanced migration and podia
      formation, v) enhanced tumorigenicity, and vi) bi-potential development (tumor
      cells and stroma-like cells), suggesting that they have cancer stem-like cell
      features. Recently, we demonstrated that sodium butyrate, a histone deacetylase
      (HDAC) inhibitor, inhibited the self-renewal capacity of endometrial cancer SP
      cells by inducing a DNA damage response. Here, we review recent articles that
      show the presence of stem cells in normal endometrium and endometrial cancer and
      introduce the results of our own recent studies.

PMID- 22641665
TI  - Heat-shock protein 27 plays the key role in gemcitabine-resistance of pancreatic
      cancer cells.
AB  - Pancreatic cancer is one of the most fatal types of cancer in developed
      countries. Most patients have locally advanced or metastatic cancerous lesions
      when they are diagnosed, due to the progressive, invasive and metastatic capacity
      of this disease to liver, lymph nodes and distant organs during early stages.
      Although the only curative therapy is complete surgical resection, the disease
      has usually already progressed by the time of diagnosis, and the majority of
      patients have metastatic disease. Therefore, palliative chemotherapy remains the
      only therapy for patients with progressive disease. Gemcitabine has been used for
      pancreatic cancer as the most effective anticancer drug. However, there are many
      cases resistant to gemcitabine. Thus, a better understanding of the molecular
      mechanisms of resistance to gemcitabine is essential to allow it to be used more
      effectively. Our previous proteomic studies demonstrated that the expression of
      heat-shock protein 27 (HSP27) was increased in gemcitabine-resistant pancreatic
      cancer cells and this might play a role in determining the sensitivity of
      pancreatic cancer to gemcitabine. Increased HSP27 expression in tumor specimens
      was related to resistance to gemcitabine and a shorter survival period in
      patients with pancreatic cancer. Furthermore, it has been shown that treatment
      strategies combining the HSP inhibitor KNK437 or interferon-gamma (IFN-gamma)
      with gemcitabine, were effective in gemcitabine-resistant pancreatic cancer cells
      in vitro. Furthermore, combined therapy of gemcitabine with IFN-gamma of
      gemcitabine-resistant pancreatic cancer-bearing nude mice showed synergistic
      therapeutic effects on gemcitabine-resistant pancreatic cancer bearers. In this
      review, we summarize the current understanding of HSP27 and its role in
      gemcitabine resistance.

PMID- 22641666
TI  - ALPK2 is crucial for luminal apoptosis and DNA repair-related gene expression in
      a three-dimensional colonic-crypt model.
AB  - BACKGROUND: Oncogenic KRAS signaling is dysregulated in a three-dimensional (3D)
      specific manner in human colorectal cancer (CRC) HCT116 cells. However, the
      identity of the crucial genes which are down-regulated through oncogenic KRAS in
      3D cultures remains unclear. MATERIALS AND METHODS: We established a specific
      anti-alpha-kinase 2 (ALPK2) antibody and addressed the ALPK2 function in HKe3
      cells, which are HCT116 cells with a disruption in oncogenic KRAS, in a 3D
      colonic-crypt model. RESULTS: In HKe3 cells grown in 3D culture, ALPK2 siRNA
      inhibited luminal apoptosis and reduced the expression of cleaved caspase-3.
      Furthermore, ALPK2 siRNA reduced the expression of DNA repair genes. Reduced
      expression of ALPK2 mRNA was found to be correlated with clinical colorectal
      adenomas in a public dataset of gene expression analyses. CONCLUSION: ALPK2, down
      regulated by oncogenic KRAS, is crucial for luminal apoptosis and expression of
      DNA repair-related genes, possibly in the transition of normal colonic crypt to
      adenoma.

PMID- 22641667
TI  - Increased claudin-1 protein expression in hepatic metastatic lesions of
      colorectal cancer.
AB  - BACKGROUND: The molecular and morphological alterations of the tight junctions in
      hepatic metastatic lesions are poorly understood. The possible involvement of
      claudin-1 (CL-1), which is one of the major tight junctional proteins, was
      investigated in the tumorigenesis of hepatic metastasis in patients with
      colorectal cancer (CRC). PATIENTS AND METHODS: A total of 14 patients with
      hepatic metastasis of CRC who underwent surgical treatment from January 2007
      until December 2010 at the Kurume University Hospital in Fukuoka, were examined.
      CRC tissue specimens were analyzed to determine whether the levels of CL-1
      correlated with clinicopathological factors and to determine the roles of CL-1,
      beta-catenin, and E-cadherin in the alterations of the tight junctions during
      tumorigenesis. RESULTS: In seven cases, the tumors were located in the colon,
      while the other seven tumors were found in the rectum. There were eight cases of
      synchronous liver metastasis, while there were six cases of metachronous liver
      metastasis. The levels of the CL-1 protein were up-regulated in CRC and in
      hepatic metastatic lesions. The levels of beta-catenin were positive or up
      regulated in the primary CRC lesions and in hepatic metastatic lesions. Despite
      the finding that the levels of E-cadherin were decreased in CRC, they were
      clearly up-regulated in hepatic metastatic lesions in this study. CONCLUSION:
      This study demonstrated that CL-1 levels were up-regulated in liver metastatic
      lesions from primary CRC lesions. Moreover, the levels of E-cadherin were
      increased in liver metastatic lesions, which may point to the existence of
      interactions between CL-1 and E-cadherin in hepatic metastatic lesions. These
      observations suggest that CL-1 plays a pivotal role in the regulation of cellular
      morphology and in the behavior of metastatic processes in CRC.

PMID- 22641668
TI  - Amphiregulin is a prognostic factor in colorectal cancer.
AB  - Amphiregulin is an epidermal growth factor (EGF) which is a ligand of epidermal
      growth factor receptor (EGFR). Amphiregulin is the most enhanced EGFR ligand in
      colon cancer. Here we report on the expression of Amphiregulin using
      immunohistochemical staining in primary colorectal cancer, and the correlations
      between prognosis and various clinicopathological factors. We examined 174
      consecutive patients who underwent curative resection of colorectal cancer, from
      January 2002 to December 2004. Amphiregulin was positive in 156 (90%) patients.
      Amphiregulin was found to be an independent predictor of overall survival [hazard
      ratio=6.25 (95% confidence interval=1.3-111.5; p=0.0144)] and relapse-free
      survival [hazard ratio=6.94 (95% confidence interval=1.5-123.2; p=0.0075)]. We
      conclude that the expression of Amphiregulin in a primary colorectal tumor is
      useful as an indicator of prognosis and as a predictor of recurrence.

PMID- 22641669
TI  - Investigation of a bacterial pore-forming chimera toxin for application as a
      novel drug-delivery system tool.
AB  - BACKGROUND/AIM: Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins
      from Gram-positive bacteria. The aim of this study was to investigate the
      potential of a CDC, intermedilysin, as a drug-delivery system (DDS) for clinical
      application. MATERIALS AND METHODS: Intermedilysin was modified by the addition
      of a disulfide bridge to regulate pore formation, by swapping domain 4 to provide
      cholesterol-binding capacity, and by the introduction of a targeting domain. The
      resultant chimera protein, His-LTBP-CDC(ss)(IP), was investigated for its use as
      a DDS tool in vitro. RESULTS: His-LTBP-CDC(ss)(IP) exhibited a regulated pore
      forming capacity under reducing conditions. This chimera protein was able to
      deliver a drug-carrier liposome specifically to the target cell, to be
      endocytosed into the cell with subsequent release of the components into the
      cytoplasm. CONCLUSION: A chimera protein derived from the bacterial pore-forming
      toxin intermedilysin (His-LTBP-CDC(ss)(IP)) forms the basis for a novel DDS tool.

PMID- 22641670
TI  - Short-term and low-dose prednisolone administration reduces aromatase inhibitor
      induced arthralgia in patients with breast cancer.
AB  - Aromatase inhibitors (AIs) are important therapeutic drugs for postmenopausal
      women with hormone receptor-positive breast cancer. However, adverse effects of
      AIs such as arthralgia have been extensively reported. We performed a joint
      prospective, multi-institutional investigation to find out whether a low-dose and
      short-term prednisolone is effective against AI-induced arthralgia in 27 patients
      with breast cancer. Patients were administered 5 mg of oral prednisolone once a
      day in the morning for only one week. Patients were then asked to answer a
      questionnaire about joint pain symptoms at one week, one month and two months
      after the beginning of prednisolone use. Joint pain symptoms improved in 67% of
      patients immediately after prednisolone use, with 63% still reporting analgesic
      effect at one month, and 52% at two months after beginning internal use of
      prednisolone. At one week, one month and two months after the use of
      prednisolone, 30%, 30% and 26% of patients reported improved daily life,
      respectively. Our results suggest that prednisolone could substitute non
      steroidal anti-inflammatory drugs, acetoaminophen or cyclooxygenase-2 inhibitors
      in patients with AI-induced arthralgia.

PMID- 22641671
TI  - The involvement of O-antigen polysaccharide in lipopolysaccharide in macrophage
      activation.
AB  - Bacterial lipopolysaccharide (LPS), which is generally considered to be an
      endotoxin, is the major constituent of the outer membrane of Gram-negative
      bacteria. The structure of LPS consists of three regions; lipid A, core
      oligosaccharide and O-antigen polysaccharide (O-PS). The structures of lipid A
      and core oligosaccharide are highly conserved among bacterial genera, but that of
      O-PS varies and differs in common bacterial species. Although studies of the
      biological activities of LPS have mainly focused on the lipid A moiety, a recent
      study gradually clarified the importance of O-PS to elicit the biological
      activities. In this review, we summarize previous studies on the correlation
      between the structure of O-PS and the biological activity of LPS, and discuss the
      possibility of innovative drug development using modified and synthetic LPS.

PMID- 22641672
TI  - Molecular profiles of cholesterol-dependent cytolysin family-derived 11mer
      regions.
AB  - BACKGROUND: Cholesterol-dependent cytolysins (CDCs) are secreted from various
      types of bacteria and are involved in various diseases (e.g. abscess formation).
      Traditional CDCs has a conserved 11mer region, which is a key structure in
      membrane recognition. MATERIALS AND METHODS: Based on the X-ray data of
      traditional CDC perfringolysin O (PFO), molecular models of intermedilysin (ILY),
      pyolysin (PLO), vaginolysin (VLY), and Streptococcus mitis-derived human platelet
      aggregation factor (Sm-hPAF) were constructed. The 11mer regions of these models
      were extracted, and their molecular features were analyzed. RESULTS: The dipole
      moments of these 11mer regions were classified into four types, and their stereo
      hydrophobicity (dGW) was different. It was thought that these results influenced
      the species specificity and membrane recognition of each cytolysin. CONCLUSION:
      Traditional CDCs, ILY, PLO, and VLY consisted of four domains (domains 1 to 4).
      Domain 0 existed on the N-terminal side in Sm-hPAF in addition to these four
      domains. The 11mer sequence of Sm-hPAF is the same as that of VLY, but Sm-hPAF
      has slightly different characteristics (e.g. species specificity, membrane
      recognition, cholesterol dependency) compared to VLY. Dynamic structure analysis
      of domain 0 might clarify these differences.

PMID- 22641673
TI  - Regulatory mechanisms of the HB-EGF autocrine loop in inflammation, homeostasis,
      development and cancer.
AB  - Heparin binding epidermal growth factor-like growth factor (HB-EGF) is involved
      in development and homeostasis as well as in pathological processing of chronic
      diseases, especially cancer. Enhancement of HB-EGF expression is directly or
      indirectly regulated by transcriptional factors, including activator protein-1
      (AP-1), specificity protein (SP)1, SP3, nuclear factor kappa B (NF-kappaB),
      hypoxia inducible factor 1, alpha subunit (HIF-1alpha, myogenic differentiation 1
      (MyoD), Wilms tumor 1 (WT-1) and snail homolog 1 (Snail), and also by microRNAs.
      These transcription or post-transcription factors may communicate to form an
      autocrine HB-EGF amplification loop. Emerging evidence has indicated that HB-EGF
      is a rational target for the therapy of cancer and atherosclerosis. In this
      review, we discuss the relationship between the HB-EGF autocrine loop and HB-EGF
      transcriptional factors, and we highlight HB-EGF as a therapeutic target in
      diverse diseases.

PMID- 22641674
TI  - Clinical significance of cell-free and concentrated ascites re-infusion therapy
      for advanced and recurrent gynecological cancer.
AB  - BACKGROUND: The management of malignant ascites is critical for the treatment of
      patients with advanced gynecological cancer. The purpose of this study was to
      assess the clinical significance of cell-free and concentrated ascites re
      infusion therapy (CART). PATIENTS AND METHODS: Adverse events, alterations in
      Eastern Cooperative Oncology Group performance status, serum albumin, body weight
      and abdominal circumference, and overall survival were examined in 22 patients
      with advanced gynecological cancer which were treated with CART. RESULTS: Most of
      the adverse events were grade 1 or 2 fever. CART treatment had little effect on
      ECOG performance status and on levels of serum albumin. There was a significant
      decrease in body weight and in abdominal circumference post-treatment with CART,
      relative to pre-treatment (p<0.01). The overall survival rate was significantly
      prolonged in 14 patients after CART plus chemotherapy, as compared with eight
      patients after CART alone (p<0.01). CONCLUSION: CART may contribute to the
      improvement of quality of life and of survival in patients with advanced
      gynecological cancer.

PMID- 22641675
TI  - beta-Galactosidase treatment is a common first-stage modification of the three
      major subtypes of Gc protein to GcMAF.
AB  - BACKGROUND: The 1f1f subtype of the group-specific component (Gc) protein is
      converted into Gc protein-derived macrophage-activating factor (GcMAF) by
      enzymatic processing with beta-galactosidase and sialidase. We previously
      demonstrated that preGc(1f1f)MAF, a full Gc(1f1f) protein otherwise lacking a
      galactosyl moiety, can be converted to GcMAF by treatment with mouse peritoneal
      fluid. Here, we investigated the effects of the beta-galactosidase-treated 1s1s
      and 22 subtypes of Gc protein (preGc(1s1s)MAF and preGc22MAF) on the phagocytic
      activation of mouse peritoneal macrophages. RESULTS: We demonstrated the presence
      of Gal-GalNAc disaccharide sugar structures in the Gc(1s1s) protein by western
      blotting using peanut agglutinin and Helix pomatia agglutinin lectin. We also
      found that preGc(1s1s)MAF and preGc22MAF significantly enhanced the phagocytic
      activity of mouse peritoneal macrophages in the presence and absence of mouse
      peritoneal fluid. CONCLUSION: We demonstrate that preGc(1s1s)MAF and preGc22MAF
      proteins can be used as effective macrophage activators.

PMID- 22641676
TI  - The effect of lentinan combination therapy for unresectable advanced gastric
      cancer.
AB  - BACKGROUND: Developed as a biological response modifier (BRM), lentinan mitigates
      patients' symptoms by boosting the immune system. In combination with S-1
      (tegafur, gimeracil, oteracil), lentinan is reported to mitigate adverse
      reactions to therapy for unresectable recurrent gastric cancer and prolong
      survival. However, there are few reports from actual clinical practice, and
      precise methods of using lentinan have not yet been established. This study
      retrospectively examined the usefulness of lentinan in patients. PATIENTS AND
      METHODS: The subjects of this study were 39 patients who were diagnosed with
      unresectable gastric cancer, based on preoperative examinations or findings at
      laparotomy in our Department. These patients underwent S-1/paclitaxel therapy.
      Nineteen of the patients received lentinan while 20 did not, and these two groups
      of patients were compared. RESULTS: There were no significant differences in
      patients' characteristics such as the male:female ratio, age at the start of
      chemotherapy, and staging classification of the 19 patients receiving lentinan
      and the 20 patients not receiving lentinan. Comparison of the two groups revealed
      no significant differences in overall survival time, but comparison of the
      duration of therapy revealed that therapy tended to be longer for the group
      taking lentinan than the group not taking lentinan. Adverse events were noted in
      61.5% (24 patients) of the total patients group; such events tended to occur less
      frequently in the group receiving lentinan. CONCLUSION: Lentinan inclusion in
      therapy did not seem to prolong survival. Nevertheless, the duration of therapy
      tended to be longer for patients taking lentinan. This may be due to the fact
      that adverse events tended to occur less frequently in these patients during
      therapy. A decline in the incidence of adverse events increases the duration of
      therapy and improves the patients' quality of life (QOL); it may also prolong
      survival. Optimal methods of using lentinan need to be established.

PMID- 22641677
TI  - Effect of green tea extract on reactive oxygen species produced by neutrophils
      from cancer patients.
AB  - BACKGROUND/AIM: Oxidative stress in cancer patients has been demonstrated to be
      partly mediated by neutrophils. Although it is reported that natural
      antioxidants, such as green tea extract, reduce oxidative stress, there is
      limited evidence of their effects in cancer patients. This study aimed to
      determine the effect of green tea extract on reactive oxygen species produced by
      neutrophils from cancer patients. MATERIALS AND METHODS: Peripheral blood samples
      were obtained from eighteen patients with advanced cancer. Green tea extract was
      added to the blood samples with luminol on Mebiol gel, and luminol-dependent
      chemiluminescence was measured to monitor the production of reactive oxygen
      species from migrated neutrophils into the gel, at 37 degrees C. RESULTS: Luminol
      dependent chemiluminescence was significantly down-regulated in the presence of
      green tea extract in a concentration-dependent manner. CONCLUSION: These results
      indicate the antioxidant effect of green tea extract on reactive oxygen species
      produced by neutrophils, which may be effective in reducing oxidative stress in
      cancer patients.

PMID- 22641678
TI  - Functional design of chimeric T-cell antigen receptors for adoptive immunotherapy
      of cancer: architecture and outcomes.
AB  - Adoptive immunotherapy using genetically modified T-cells with a chimeric antigen
      receptor (CAR) is a promising modality for cancer treatment, because the CAR
      grafted T-cells can directly recognize and kill tumor cells, expressing a
      specific tumor-associated antigen (TAA), in a human leukocyte antigen (HLA)
      independent manner. Optimal molecular designs of the CAR and a careful choice of
      the target TAA are requisite to attain a significant response in CAR-mediated
      therapy. This review provides a brief overview of the past studies and the
      present state of CAR research, especially focusing on the development of the CAR
      protein architecture.

PMID- 22641679
TI  - A new method for rapid cytotoxic T-lymphocyte induction using a multiple cytokine
      cocktail.
AB  - Immunotherapy using cytotoxic T-lymphocytes (CTLs) still has limited success. An
      increase in the frequency of CTL administration is one method to improve
      immunotherapy using CTLs. The conventional method (C-method) that generates CTLs
      after the induction of dendritic cells requires a long time period. If CTLs can
      be more rapidly and simply induced, the frequency of immunotherapy could be
      increased and unexpected contamination could be avoided. In this study, in order
      to more rapidly induce functional CTLs, we investigated a new method (N-method)
      that uses a cytokine cocktail, including interleukin (IL)-2, IL-4, granulocyte
      macrophage colony-stimulating factor, tumour necrosis factor-alpha and interferon
      alpha, together with a tumour lysate. CTLs induced by the N-method had equivalent
      functions, such as proliferation, surface antigen expression and cytotoxicity,
      compared with those induced by the C-method. These results suggest that the N
      method can substitute the C-method in order to improve the effect of
      immunotherapy using CTLs.

PMID- 22641680
TI  - Measles.

PMID- 22641681
TI  - Coal workers' pneumoconiosis with progressive massive fibrosis.

PMID- 22641683
TI  - Antiretroviral medication for preventing HIV infection in nonoccupational
      settings.

PMID- 22641684
TI  - India makes tuberculosis a notifiable disease.

PMID- 22641685
TI  - Professionalism: the "good doctor" discussion.

PMID- 22641687
TI  - Arm-twisting medical schools for core geriatric training.

PMID- 22641686
TI  - Effects of assessing the productivity of faculty in academic medical centres: a
      systematic review.
AB  - BACKGROUND: Many academic medical centres have introduced strategies to assess
      the productivity of faculty as part of compensation schemes. We conducted a
      systematic review of the effects of such strategies on faculty productivity.
      METHODS: We searched the MEDLINE, Healthstar, Embase and PsycInfo databases from
      their date of inception up to October 2011. We included studies that assessed
      academic productivity in clinical, research, teaching and administrative
      activities, as well as compensation, promotion processes and satisfaction.
      RESULTS: Of 531 full-text articles assessed for eligibility, we included 9
      articles reporting on eight studies. The introduction of strategies for assessing
      academic productivity as part of compensation schemes resulted in increases in
      clinical productivity (in six of six studies) in terms of clinical revenue, the
      work component of relative-value units (these units are nonmonetary standard
      units of measure used to indicate the value of services provided), patient
      satisfaction and other departmentally used standards. Increases in research
      productivity were noted (in five of six studies) in terms of funding and
      publications. There was no change in teaching productivity (in two of five
      studies) in terms of educational output. Such strategies also resulted in
      increases in compensation at both individual and group levels (in three studies),
      with two studies reporting a change in distribution of compensation in favour of
      junior faculty. None of the studies assessed effects on administrative
      productivity or promotion processes. The overall quality of evidence was low.
      INTERPRETATION: Strategies introduced to assess productivity as part of a
      compensation scheme appeared to improve productivity in research activities and
      possibly improved clinical productivity, but they had no effect in the area of
      teaching. Compensation increased at both group and individual levels,
      particularly among junior faculty. Higher quality evidence about the benefits and
      harms of such assessment strategies is needed.

PMID- 22641688
TI  - Professionalism: what is it?

PMID- 22641689
TI  - Autophagy and cancer--issues we need to digest.
AB  - Autophagy is an evolutionarily conserved catabolic pathway that has multiple
      roles in carcinogenesis and cancer therapy. It can inhibit the initiation of
      tumorigenesis through limiting cytoplasmic damage, genomic instability and
      inflammation, and the loss of certain autophagy genes can lead to cancer.
      Conversely, autophagy can also assist cells in dealing with stressful metabolic
      environments, thereby promoting cancer cell survival. In fact, some cancers rely
      on autophagy to survive and progress. Furthermore, tumour cells can exploit
      autophagy to cope with the cytotoxicity of certain anticancer drugs. By contrast,
      it appears that certain therapeutics require autophagy for the effective killing
      of cancer cells. Despite these dichotomies, it is clear that autophagy has an
      important, if complex, role in cancer. This is further exemplified by the fact
      that autophagy is connected with major cancer networks, including those driven by
      p53, mammalian target of rapamycin (mTOR), RAS and glutamine metabolism. In this
      Commentary, we highlight recent advances in our understanding of the role that
      autophagy has in cancer and discuss current strategies for targeting autophagy
      for therapeutic gain.

PMID- 22641690
TI  - Confluence switch signaling regulates ECM composition and the plasmin proteolytic
      cascade in keratinocytes.
AB  - In culture, cell confluence generates signals that commit actively growing
      keratinocytes to exit the cell cycle and differentiate to form a stratified
      epithelium. Using a comparative proteomic approach, we studied this 'confluence
      switch' and identified a new pathway triggered by cell confluence that regulates
      basement membrane (BM) protein composition by suppressing the uPA-uPAR-plasmin
      pathway. Indeed, confluence triggers adherens junction maturation and enhances
      TGF-beta and activin A activity, resulting in increased deposition of PAI-1 and
      perlecan in the BM. Extracellular matrix (ECM)-accumulated PAI-1 suppresses the
      uPA-uPAR-plasmin pathway and further enhances perlecan deposition by inhibiting
      its plasmin-dependent proteolysis. We show that perlecan deposition in the ECM
      strengthens cell adhesion, inhibits keratinocyte motility and promotes additional
      accumulation of PAI-1 in the ECM at confluence. In agreement, during wound
      healing, perlecan concentrates at the wound-margin, where BM matures to stabilize
      keratinocyte adhesion. Our results demonstrate that confluence-dependent
      signaling orchestrates not only growth inhibition and differentiation, but also
      controls ECM proteolysis and BM formation. These data suggest that uncontrolled
      integration of confluence-dependent signaling, might favor skin disorders,
      including tumorigenesis, not only by promoting cell hyperproliferation, but also
      by altering protease activity and deposition of ECM components.

PMID- 22641691
TI  - Regulation of apoptosis by Bat3-enhanced YWK-II/APLP2 protein stability.
AB  - YWK-II protein/APLP2 is a member of an evolutionarily conserved protein family
      that includes amyloid precursor protein (APP) and amyloid precursor-like protein
      1 (APLP1). We have previously demonstrated that YWK-II/APLP2 functions as a novel
      G(0)-protein-coupled receptor for Mullerian inhibiting substance (MIS) in cell
      survival. However, factors regulating the stability and turnover of YWK-II/APLP2
      have not been identified. Here we present evidence that human leukocyte antigen-B
      associated transcript 3 (Bat3), an important regulator involved in apoptosis, can
      interact with YWK-II/APLP2 and enhance its stability by reducing its
      ubiquitylation and degradation by the ubiquitin-proteasome system. Coexpression
      of different Bat3 domain deletion constructs with YWK-II/APLP2 reveals that the
      proline-rich domain of Bat3 is required for its binding to YWK-II/APLP2. In
      addition, we find that the protein levels of YWK-II/APLP2 could be enhanced by
      nuclear export of Bat3 under apoptotic stimulation. We also find elevated levels
      of Bat3 and YWK-II/APLP2 in human colorectal cancer with a positive correlation
      between the two. Taken together, these results have revealed a previously
      undefined mechanism regulating cell apoptosis and suggest that aberrant
      enhancement of YWK-II/APLP2 by nuclear export of Bat3 may play a role in cancer
      development by inhibiting cell apoptosis.

PMID- 22641692
TI  - Sonic hedgehog regulates presynaptic terminal size, ultrastructure and function
      in hippocampal neurons.
AB  - Sonic hedgehog (Shh) signaling is essential to the patterning of the embryonic
      neural tube, but its presence and function in the postmitotic differentiated
      neurons in the brain remain largely uncharacterized. We recently showed that Shh
      and its signaling components, Patched and Smoothened, are expressed in postnatal
      and adult hippocampal neurons. We have now examined whether Shh signaling has a
      function in these neurons. Using cultured hippocampal neurons as a model system,
      we found that presynaptic terminals become significantly larger in response to
      the application of Shh. Ultrastructural examination confirmed the enlarged
      presynaptic profiles and also revealed variable increases in the size of synaptic
      vesicles, with a resulting loss of uniformity. Furthermore, electrophysiological
      analyses showed significant increases in the frequency, but not the amplitude, of
      spontaneous miniature excitatory postsynaptic currents (mEPSCs) in response to
      Shh, providing functional evidence of the selective role of Shh in presynaptic
      terminals. Thus, we conclude that Shh signaling regulates the structure and
      functional properties of presynaptic terminals of hippocampal neurons.

PMID- 22641693
TI  - Bone morphogenetic proteins differentially regulate pigmentation in human skin
      cells.
AB  - Bone morphogenetic proteins (BMPs) are a large family of multi-functional
      secreted signalling molecules. Previously BMP2/4 were shown to inhibit skin
      pigmentation by downregulating tyrosinase expression and activity in epidermal
      melanocytes. However, a possible role for other BMP family members and their
      antagonists in melanogenesis has not yet been explored. In this study we show
      that BMP4 and BMP6, from two different BMP subclasses, and their antagonists
      noggin and sclerostin were variably expressed in melanocytes and keratinocytes in
      human skin. We further examined their involvement in melanogenesis and melanin
      transfer using fully matched primary cultures of adult human melanocytes and
      keratinocytes. BMP6 markedly stimulated melanogenesis by upregulating tyrosinase
      expression and activity, and also stimulated the formation of filopodia and
      Myosin-X expression in melanocytes, which was associated with increased
      melanosome transfer from melanocytes to keratinocytes. BMP4, by contrast,
      inhibited melanin synthesis and transfer to below baseline levels. These findings
      were confirmed using siRNA knockdown of BMP receptors BMPR1A/1B or of Myosin-X,
      as well as by incubating cells with the antagonists noggin and sclerostin. While
      BMP6 was found to use the p38MAPK pathway to regulate melanogenesis in human
      melanocytes independently of the Smad pathway, p38MAPK, PI3-K and Smad pathways
      were all involved in BMP6-mediated melanin transfer. This suggests that pigment
      formation may be regulated independently of pigment transfer. These data reveal a
      complex involvement of regulation of different members of the BMP family, their
      antagonists and inhibitory Smads, in melanocytes behaviour.

PMID- 22641695
TI  - Toxofilin upregulates the host cortical actin cytoskeleton dynamics, facilitating
      Toxoplasma invasion.
AB  - Toxoplasma gondii, a human pathogen and a model apicomplexan parasite, actively
      and rapidly invades host cells. To initiate invasion, the parasite induces the
      formation of a parasite-cell junction, and progressively propels itself through
      the junction, inside a newly formed vacuole that encloses the entering parasite.
      Little is known about how a parasite that is a few microns in diameter overcomes
      the host cell cortical actin barrier to achieve the remarkably rapid process of
      internalization (less than a few seconds). Using correlative light and electron
      microscopy in conjunction with electron tomography and three-dimensional image
      analysis we identified that toxofilin, an actin-binding protein, secreted by
      invading parasites correlates with localized sites of disassembly of the host
      cell actin meshwork. Moreover, quantitative fluorescence speckle microscopy of
      cells expressing toxofilin showed that toxofilin regulates actin filament
      disassembly and turnover. Furthermore, Toxoplasma tachyzoites lacking toxofilin,
      were found to be impaired in cortical actin disassembly and exhibited delayed
      invasion kinetics. We propose that toxofilin locally upregulates actin turnover
      thus increasing depolymerization events at the site of entry that in turn loosens
      the local host cell actin meshwork, facilitating parasite internalization and
      vacuole folding.

PMID- 22641694
TI  - Formation of telomeric repeat-containing RNA (TERRA) foci in highly proliferating
      mouse cerebellar neuronal progenitors and medulloblastoma.
AB  - Telomeres play crucial roles in the maintenance of genome integrity and control
      of cellular senescence. Most eukaryotic telomeres can be transcribed to generate
      a telomeric repeat-containing RNA (TERRA) that persists as a heterogeneous
      nuclear RNA and can be developmentally regulated. However, the precise function
      and regulation of TERRA in normal and cancer cell development remains poorly
      understood. Here, we show that TERRA accumulates in highly proliferating normal
      and cancer cells, and forms large nuclear foci, which are distinct from
      previously characterized markers of DNA damage or replication stress. Using a
      mouse model for medulloblastoma driven by chronic Sonic hedgehog (SHH) signaling,
      TERRA RNA was detected in tumor, but not adjacent normal cells using both RNA
      fluorescence in situ hybridization (FISH) and northern blotting. RNA FISH
      revealed the formation of TERRA foci (TERFs) in the nuclear regions of rapidly
      proliferating tumor cells. In the normal developing cerebellum, TERRA aggregates
      could also be detected in highly proliferating zones of progenitor neurons. SHH
      could enhance TERRA expression in purified granule progenitor cells in vitro,
      suggesting that proliferation signals contribute to TERRA expression in
      responsive tissue. TERRA foci did not colocalize with gammaH2AX foci,
      promyelocytic leukemia (PML) or Cajal bodies in mouse tumor tissue. We also
      provide evidence that TERRA is elevated in a variety of human cancers. These
      findings suggest that elevated TERRA levels reflect a novel early form of
      telomere regulation during replication stress and cancer cell evolution, and the
      TERRA RNA aggregates may form a novel nuclear body in highly proliferating
      mammalian cells.

PMID- 22641697
TI  - The lysosomal polypeptide transporter TAPL is stabilized by interaction with LAMP
      1 and LAMP-2.
AB  - TAPL (ABCB9) is a homodimeric polypeptide translocation machinery which
      transports cytosolic peptides into the lumen of lysosomes for degradation. Since
      the function of proteins is strongly dependent on the interaction network
      involved, we investigated the interactome of TAPL. A proteomic approach allowed
      identification of the lysosome-associated membrane proteins LAMP-1 and LAMP-2B as
      the most abundant interaction partners. Albeit with low frequency, major
      histocompatibility complex II subunits were also detected. The interaction
      interface with LAMP was mapped to the four-transmembrane helices constituting the
      N-terminal domain of TAPL (TMD0). The LAMP proteins bind independently to TAPL.
      This interaction has influence on neither subcellular localization nor peptide
      transport activity. However, in LAMP-deficient cells, the half-life of TAPL is
      decreased by a factor of five, whereas another lysosomal membrane protein, LIMP
      2, is not affected. Reduced stability of TAPL is caused by increased lysosomal
      degradation, indicating that LAMP proteins retain TAPL on the limiting membrane
      of endosomes and prevent its sorting to intraluminal vesicles.

PMID- 22641696
TI  - Alternative translation initiation gives rise to two isoforms of Orai1 with
      distinct plasma membrane mobilities.
AB  - Store-operated calcium entry is an almost ubiquitous signaling pathway in
      eukaryotic cells. The plasma membrane store-operated channels are comprised of
      subunits of the recently discovered Orai proteins, the major one being Orai1.We
      have discovered that native Orai1, as well as expressed Orai1, exists in two
      forms in similar quantities: a longer form (Orai1alpha) of approximately 33 kDa,
      and a shorter form (Orai1beta) of approximately 23 kDa. The Orai1beta form arises
      from alternative translation initiation from a methionine at position 64, and
      possibly also 71, in the longer Orai1alpha form. In the sequence upstream of the
      initiation site of Orai1beta, there is a poly-arginine sequence previously
      suggested to be involved in interaction of Orai1 with plasma membrane
      phosphatidylinositol-4,5-bisphosphate. The loss of this phospholipid binding
      domain would be expected to influence the mobility of Orai1 protein in the plasma
      membrane. Indeed, experiments utilizing fluorescence recovery after
      photobleaching (FRAP) revealed that the recovery half-time for Orai1beta was
      significantly faster than for Orai1alpha. Since Orai1 must diffuse to sites of
      interaction with the Ca(2+) sensor, STIM1, these two mobilities might provide for
      efficient recruitment of Orai1 subunits to sites of store-operated Ca(2+) entry
      during agonist-induced Ca(2+) signaling.

PMID- 22641698
TI  - Efficient computation of robust weighted low-rank matrix approximations using the
      L1 norm.
AB  - The calculation of a low-rank approximation to a matrix is fundamental to many
      algorithms in computer vision and other fields. One of the primary tools used for
      calculating such low-rank approximations is the Singular Value Decomposition, but
      this method is not applicable in the case where there are outliers or missing
      elements in the data. Unfortunately, this is often the case in practice. We
      present a method for low-rank matrix approximation which is a generalization of
      the Wiberg algorithm. Our method calculates the rank-constrained factorization,
      which minimizes the L1 norm and does so in the presence of missing data. This is
      achieved by exploiting the differentiability of linear programs, and results in
      an algorithm can be efficiently implemented using existing optimization software.
      We show the results of experiments on synthetic and real data.

PMID- 22641699
TI  - Time Series Analysis Using Geometric Template Matching.
AB  - We present a novel framework for analyzing univariate time series data. At the
      heart of the approach is a versatile algorithm for measuring the similarity of
      two segments of time series called geometric template matching (GeTeM). First, we
      use GeTeM to compute a similarity measure for clustering and nearest-neighbor
      classification. Next, we present a semi-supervised learning algorithm that uses
      the similarity measure with hierarchical clustering in order to improve
      classification performance when unlabeled training data are available. Finally,
      we present a boosting framework called TDEBOOST, which uses an ensemble of GeTeM
      classifiers. TDEBOOST augments the traditional boosting approach with an
      additional step in which the features used as inputs to the classifier are
      adapted at each step to improve the training error. We empirically evaluate the
      proposed approaches on several datasets, such as accelerometer data collected
      from wearable sensors and ECG data. 

PMID- 22641700
TI  - Automatic caption generation for news images.
AB  - This paper is concerned with the task of automatically generating captions for
      images, which is important for many image-related applications. Examples include
      video and image retrieval as well as the development of tools that aid visually
      impaired individuals to access pictorial information. Our approach leverages the
      vast resource of pictures available on the web and the fact that many of them are
      captioned and colocated with thematically related documents. Our model learns to
      create captions from a database of news articles, the pictures embedded in them,
      and their captions, and consists of two stages. Content selection identifies what
      the image and accompanying article are about, whereas surface realization
      determines how to verbalize the chosen content. We approximate content selection
      with a probabilistic image annotation model that suggests keywords for an image.
      The model postulates that images and their textual descriptions are generated by
      a shared set of latent variables (topics) and is trained on a weakly labeled
      dataset (which treats the captions and associated news articles as image labels).
      Inspired by recent work in summarization, we propose extractive and abstractive
      surface realization models. Experimental results show that it is viable to
      generate captions that are pertinent to the specific content of an image and its
      associated article, while permitting creativity in the description. Indeed, the
      output of our abstractive model compares favorably to handwritten captions and is
      often superior to extractive methods.

PMID- 22641701
TI  - Joint depth and color camera calibration with distortion correction.
AB  - We present an algorithm that simultaneously calibrates two color cameras, a depth
      camera, and the relative pose between them. The method is designed to have three
      key features: accurate, practical, and applicable to a wide range of sensors. The
      method requires only a planar surface to be imaged from various poses. The
      calibration does not use depth discontinuities in the depth image, which makes it
      flexible and robust to noise. We apply this calibration to a Kinect device and
      present a new depth distortion model for the depth sensor. We perform experiments
      that show an improved accuracy with respect to the manufacturer's calibration.

PMID- 22641702
TI  - A novel encoding scheme for effective biometric discretization: Linearly
      Separable Subcode.
AB  - Separability in a code is crucial in guaranteeing a decent Hamming-distance
      separation among the codewords. In multibit biometric discretization where a code
      is used for quantization-intervals labeling, separability is necessary for
      preserving distance dissimilarity when feature components are mapped from a
      discrete space to a Hamming space. In this paper, we examine separability of
      Binary Reflected Gray Code (BRGC) encoding and reveal its inadequacy in tackling
      interclass variation during the discrete-to-binary mapping, leading to a tradeoff
      between classification performance and entropy of binary output. To overcome this
      drawback, we put forward two encoding schemes exhibiting full-ideal and near
      ideal separability capabilities, known as Linearly Separable Subcode (LSSC) and
      Partially Linearly Separable Subcode (PLSSC), respectively. These encoding
      schemes convert the conventional entropy-performance tradeoff into an entropy
      redundancy tradeoff in the increase of code length. Extensive experimental
      results vindicate the superiority of our schemes over the existing encoding
      schemes in discretization performance. This opens up possibilities of achieving
      much greater classification performance with high output entropy.

PMID- 22641703
TI  - Tag Completion for Image Retrieval.
AB  - Many social image search engines are based on keyword/tag matching. This is
      because tag-based image retrieval (TBIR) is not only efficient but also
      effective. The performance of TBIR is highly dependent on the availability and
      quality of manual tags. Recent studies have shown that manual tags are often
      unreliable and inconsistent. In addition, since many users tend to choose general
      and ambiguous tags in order to minimize their efforts in choosing appropriate
      words, tags that are specific to the visual content of images tend to be missing
      or noisy, leading to a limited performance of TBIR. To address this challenge, we
      study the problem of tag completion, where the goal is to automatically fill in
      the missing tags as well as correct noisy tags for given images. We represent the
      image-tag relation by a tag matrix, and search for the optimal tag matrix
      consistent with both the observed tags and the visual similarity. We propose a
      new algorithm for solving this optimization problem. Extensive empirical studies
      show that the proposed algorithm is significantly more effective than the state
      of-the-art algorithms. Our studies also verify that the proposed algorithm is
      computationally efficient and scales well to large databases. 

PMID- 22641704
TI  - 3D Face Discriminant Analysis Using Gauss-Markov Posterior Marginals.
AB  - We present a Markov Random Field model for the analysis of lattices (e.g., images
      or 3D meshes) in terms of the discriminative information of their vertices. The
      proposed method provides a measure field that estimates the probability of each
      vertex being "discriminative" or "nondiscriminative" for a given classification
      task. To illustrate the applicability and generality of our framework, we use the
      estimated probabilities as feature scoring to define compact signatures for three
      different classification tasks: 1) 3D Face Recognition, 2) 3D Facial Expression
      Recognition, and 3) Ethnicity-based Subject Retrieval, obtaining very competitive
      results. The main contribution of this work lies in the development of a novel
      framework for feature selection in scenaria in which the most discriminative
      information is smoothly distributed along a lattice. 

PMID- 22641705
TI  - Identifying behaviors in crowd scenes using stability analysis for dynamical
      systems.
AB  - method is proposed for identifying five crowd behaviors (bottlenecks,
      fountainheads, lanes, arches, and blocking) in visual scenes. In the algorithm, a
      scene is overlaid by a grid of particles initializing a dynamical system defined
      by the optical flow. Time integration of the dynamical system provides particle
      trajectories that represent the motion in the scene; these trajectories are used
      to locate regions of interest in the scene. Linear approximation of the dynamical
      system provides behavior classification through the Jacobian matrix; the
      eigenvalues determine the dynamic stability of points in the flow and each type
      of stability corresponds to one of the five crowd behaviors. The eigenvalues are
      only considered in the regions of interest, consistent with the linear
      approximation and the implicated behaviors. The algorithm is repeated over
      sequential clips of a video in order to record changes in eigenvalues, which may
      imply changes in behavior. The method was tested on over 60 crowd and traffic
      videos.

PMID- 22641706
TI  - SLIC superpixels compared to state-of-the-art superpixel methods.
AB  - Computer vision applications have come to rely increasingly on superpixels in
      recent years, but it is not always clear what constitutes a good superpixel
      algorithm. In an effort to understand the benefits and drawbacks of existing
      methods, we empirically compare five state-of-the-art superpixel algorithms for
      their ability to adhere to image boundaries, speed, memory efficiency, and their
      impact on segmentation performance. We then introduce a new superpixel algorithm,
      simple linear iterative clustering (SLIC), which adapts a k-means clustering
      approach to efficiently generate superpixels. Despite its simplicity, SLIC
      adheres to boundaries as well as or better than previous methods. At the same
      time, it is faster and more memory efficient, improves segmentation performance,
      and is straightforward to extend to supervoxel generation.

PMID- 22641707
TI  - A visual-attention model using Earth Mover's Distance-based saliency measurement
      and nonlinear feature combination.
AB  - This paper introduces a new computational visual-attention model for static and
      dynamic saliency maps. First, we use the Earth Mover's Distance (EMD) to measure
      the center-surround difference in the receptive field, instead of using the
      Difference-of-Gaussian filter that is widely used in many previous visual
      attention models. Second, we propose to take two steps of biologically inspired
      nonlinear operations for combining different features: combining subsets of basic
      features into a set of super features using the Lm-norm and then combining the
      super features using the Winner-Take-All mechanism. Third, we extend the proposed
      model to construct dynamic saliency maps from videos by using EMD for computing
      the center-surround difference in the spatiotemporal receptive field. We evaluate
      the performance of the proposed model on both static image data and video data.
      Comparison results show that the proposed model outperforms several existing
      models under a unified evaluation setting.

PMID- 22641708
TI  - Improving the prediction of clinical outcomes from genomic data using
      multiresolution analysis.
AB  - The prediction of patient's future clinical outcome, such as Alzheimer's and
      cardiac disease, using only genomic information is an open problem. In cases when
      genome-wide association studies (GWASs) are able to find strong associations
      between genomic predictors (e.g., SNPs) and disease, pattern recognition methods
      may be able to predict the disease well. Furthermore, by using signal processing
      methods, we can capitalize on latent multivariate interactions of genomic
      predictors. Such an approach to genomic pattern recognition for prediction of
      clinical outcomes is investigated in this work. In particular, we show how
      multiresolution transforms can be applied to genomic data to extract cues of
      multivariate interactions and, in some cases, improve on the predictive
      performance of clinical outcomes of standard classification methods. Our results
      show, for example, that an improvement of about 6 percent increase of the area
      under the ROC curve can be achieved using multiresolution spaces to train
      logistic regression to predict late-onset Alzheimer's disease (LOAD) compared to
      logistic regression applied directly on SNP data.

PMID- 22641709
TI  - CEDER: accurate detection of differentially expressed genes by combining
      significance of exons using RNA-Seq.
AB  - RNA-Seq is widely used in transcriptome studies, and the detection of
      differentially expressed genes (DEGs) between two classes of individuals, e.g.,
      cases versus controls, using RNA-Seq is of fundamental importance. Many
      statistical methods for DEG detection based on RNA-Seq data have been developed
      and most of them are based on the read counts mapped to individual genes. On the
      other hand, genes are composed of exons and the distribution of reads for the
      different exons can be heterogeneous. We hypothesize that the detection accuracy
      of differentially expressed genes can be increased by analyzing individual exons
      within a gene and then combining the results of the exons. We therefore developed
      a novel program, termed CEDER, to accurately detect DEGs by combining the
      significance of the exons. CEDER first tests for differentially expressed exons
      yielding a p-value for each, and then gives a score indicating the potential for
      a gene to be differentially expressed by integrating the p-values of the exons in
      the gene. We showed that CEDER can significantly increase the accuracy of
      existing methods for detecting DEGs on two benchmark RNA-Seq data sets and
      simulated datasets.

PMID- 22641710
TI  - QuickVina: accelerating AutoDock Vina using gradient-based heuristics for global
      optimization.
AB  - Predicting binding between macromolecule and small molecule is a crucial phase in
      the field of rational drug design. AutoDock Vina, one of the most widely used
      docking software released in 2009, uses an empirical scoring function to evaluate
      the binding affinity between the molecules and employs the iterated local search
      global optimizer for global optimization, achieving a significantly improved
      speed and better accuracy of the binding mode prediction compared its
      predecessor, AutoDock 4. In this paper, we propose further improvement in the
      local search algorithm of Vina by heuristically preventing some intermediate
      points from undergoing local search. Our improved version of Vina-dubbed QVina
      achieved a maximum acceleration of about 25 times with the average speed-up of
      8.34 times compared to the original Vina when tested on a set of 231 protein
      ligand complexes while maintaining the optimal scores mostly identical. Using our
      heuristics, larger number of different ligands can be quickly screened against a
      given receptor within the same time frame.

PMID- 22641711
TI  - Simultaneous identification of duplications, losses, and lateral gene transfers.
AB  - We give a fixed-parameter algorithm for the problem of enumerating all minimum
      cost LCA-reconciliations involving gene duplications, gene losses, and lateral
      gene transfers (LGTs) for a given species tree S and a given gene tree G. Our
      algorithm can work for the weighted version of the problem, where the costs of a
      gene duplication, a gene loss, and an LGT are left to the user's discretion. The
      algorithm runs in O(m + 3(k/c)n) time, where m is the number of vertices in S, n
      is the number of vertices in G, c is the smaller between a gene duplication cost
      and an LGT cost, and k is the minimum cost of an LCA-reconciliation between S and
      G. The time complexity is indeed better if the cost of a gene loss is greater
      than 0. In particular, when the cost of a gene loss is at least 0.614c, the
      running time of the algorithm is O(m + 2.78(k/c)n).

PMID- 22641712
TI  - Noniterative convex optimization methods for network component analysis.
AB  - This work studies the reconstruction of gene regulatory networks by the means of
      network component analysis (NCA). We will expound a family of convex optimization
      based methods for estimating the transcription factor control strengths and the
      transcription factor activities (TFAs). The approach taken in this work is to
      decompose the problem into a network connectivity strength estimation phase and a
      transcription factor activity estimation phase. In the control strength
      estimation phase, we formulate a new subspace-based method incorporating a choice
      of multiple error metrics. For the source estimation phase we propose a total
      least squares (TLS) formulation that generalizes many existing methods. Both
      estimation procedures are noniterative and yield the optimal estimates according
      to various proposed error metrics. We test the performance of the proposed
      algorithms on simulated data and experimental gene expression data for the yeast
      Saccharomyces cerevisiae and demonstrate that the proposed algorithms have
      superior effectiveness in comparison with both Bayesian Decomposition (BD) and
      our previous FastNCA approach, while the computational complexity is still orders
      of magnitude less than BD.

PMID- 22641713
TI  - On the hardness of counting and sampling center strings.
AB  - Given a set S of n strings, each of length l, and a nonnegative value d, we
      define a center string as a string of length l that has Hamming distance at most
      d from each string in S. The #CLOSEST STRING problem aims to determine the number
      of center strings for a given set of strings S and input parameters n, l, and d.
      We show #CLOSEST STRING is impossible to solve exactly or even approximately in
      polynomial time, and that restricting #CLOSEST STRING so that any one of the
      parameters n, ', or d is fixed leads to a fully polynomial-time randomized
      approximation scheme (FPRAS). We show equivalent results for the problem of
      efficiently sampling center strings uniformly at random (u.a.r.).

PMID- 22641714
TI  - Robust Bayesian clustering for replicated gene expression data.
AB  - Experimental scientific data sets, especially biology data, usually contain
      replicated measurements. The replicated measurements for the same object are
      correlated, and this correlation must be carefully dealt with in scientific
      analysis. In this paper, we propose a robust Bayesian mixture model for
      clustering data sets with replicated measurements. The model aims not only to
      accurately cluster the data points taking the replicated measurements into
      consideration, but also to find the outliers (i.e., scattered objects) which are
      possibly required to be studied further. A tree-structured variational Bayes (VB)
      algorithm is developed to carry out model fitting. Experimental studies showed
      that our model compares favorably with the infinite Gaussian mixture model, while
      maintaining computational simplicity. We demonstrate the benefits of including
      the replicated measurements in the model, in terms of improved outlier detection
      rates in varying measurement uncertainty conditions. Finally, we apply the
      approach to clustering biological transcriptomics mRNA expression data sets with
      replicated measurements.

PMID- 22641716
TI  - Gas-phase ion chemistry and organic chemistry-the story of a hybrid six sector
      mass spectrometer--the "AutoSpec 6F".
AB  - The AutoSpec 6F mass spectrometer is a large, floor standing instrument
      comprising a pair of commercial EBE geometry (AutoSpec) mass spectrometers
      coupled in series to provide an hybrid EBE-EBE configuration, (E and B being
      respectively electrostatic and magnetic sectors.) It was designed in close
      collaboration between Professor R. Flammang and VG Analytical in Manchester, UK.
      It was equipped with five collision cells and allowed the recording of high
      energy CID (collision induced dissociation),  MIKES (mass analyzed ion kinetic
      energy spectrometry) and NRMS (neutralization re-ionization mass spectrometry)
      data as well as consecutive MSn analyses. The field-free regions between sectors
      allowed the study of unimolecular decomposition products from long-lived
      metastable ions. The mass spectrometer became  even more versatile when an RF
      only quadrupole collision cell was installed between the second and the third
      electric sector. This allowed the study of associative ion/molecule reactions in
      the low kinetic energy regime. Bimolecular chemical reactions were performed
      inside the quadrupole cell when a neutral reagent was introduced and the reaction
      products were analyzed by high energy CID in the downstream sectors. This paper
      tells the history and summarizes the capabilities of this versatile instrument.

PMID- 22641715
TI  - Blockwise HMM computation for large-scale population genomic inference.
AB  - MOTIVATION: A promising class of methods for large-scale population genomic
      inference use the conditional sampling distribution (CSD), which approximates the
      probability of sampling an individual with a particular DNA sequence, given that
      a collection of sequences from the population has already been observed. The CSD
      has a wide range of applications, including imputing missing sequence data,
      estimating recombination rates, inferring human colonization history and
      identifying tracts of distinct ancestry in admixed populations. Most well-used
      CSDs are based on hidden Markov models (HMMs). Although computationally efficient
      in principle, methods resulting from the common implementation of the relevant
      HMM techniques remain intractable for large genomic datasets. RESULTS: To address
      this issue, a set of algorithmic improvements for performing the exact HMM
      computation is introduced here, by exploiting the particular structure of the CSD
      and typical characteristics of genomic data. It is empirically demonstrated that
      these improvements result in a speedup of several orders of magnitude for large
      datasets and that the speedup continues to increase with the number of sequences.
      The optimized algorithms can be adopted in methods for various applications,
      including the ones mentioned above and make previously impracticable analyses
      possible. AVAILABILITY: Software available upon request. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT:
      yss@eecs.berkeley.edu.

PMID- 22641717
TI  - The dissociation chemistry of ionized methyl carbamate and its isomers revisited:
      theory and experiment in concert.
AB  - Early combined computational and experimental studies by J.K. Terlouw c.s. in
      Refs. 1-3 propose that low-energy methyl carbamate ions, NH(2)COOCH(3)(*+) (MC
      1), rearrange into distonic ions NH(2)C(OH)OCH(2)(*+) and hydrogen-bridged
      radical cations [NH(2)C=O--H--OCH(2)](*+) (MC-5) en route to the observed losses
      of HCO(*) and CO. In this study, we report on the generation of ions MC-5 by
      decarbonylation of ionized methyl oxamate NH(2)COCOOCH(3)(*+). Theory and
      experiment agree that ion MC-5 is a  key intermediate in the dissociation of low
      energy ions MC-1. The subsequent HCO(*) loss, however, may not proceed via the
      route proposed in Ref. 2, but rather by an entirely different mechanism involving
      proton-transport catalysis (PTC) in ion MC-5. This view is further supported by
      the dissociation behaviour of the MC-5 isotopologue [ND(2)C=O--D--OCH(2)](*+),
      which is  conveniently generated from the d(3)-labelled glycolamide ion
      DOCH(2)C(=O)ND(2)(*+).

PMID- 22641718
TI  - Concomitant hydride and proton transfer: an essay on competing and consecutive
      key reactions occurring in gaseousion/neutral complexes.
AB  - The interplay of proton transfer and hydride transfer reactions in alkylbenzenium
      ions and related protonated di- and oligophenylalkanes is presented and
      discussed. While intra- and interannular proton exchange has been recognised to
      be an ubiquitous feature in protonated arenes, hydride abstraction is much less
      obvious but can become a dominating fragmentation channel in metastable ions of
      tert-butyl-substituted alkylbenzenium ions and related carbocations. In such
      cases, proton-induced release of the tert-butyl cation gives rise to ion/neutral
      complexes as reactive intermediates, for example,
      [(CH(3))(3)C(+)...arylCH(2)(alpha)(CH(2))(n)CH(2)(omega)aryl '] with n >= 0, and
      highly regioselective intra-complex hydride transfer occurs from all of the
      benzylic methylene hydride ion donor groups (alpha-CH(2) and omega-CH(2)) to the
      tert-butyl cation acting as a Lewis acid. Substituent effects on the individual
      contributions to the overall hydride transfer from different donor sites,
      including ortho-methyl groups, in particular, and the concomitant intra- complex
      proton transfer from the tert-butyl cation to the neutral diarylalkane
      constituent corroborate the view of "bisolvated" complexes as the central
      intermediates, in which the carbenium ion is coordinated to both of the aromatic
      pi-electron systems. The role of cyclisation processes converting the benzylic,
      [M - H](+) type, ions into the isomeric benzenium, [M + H](+)-type, ions prior to
      fragmentation is demonstrated for several cases. This overall scenario,
      consisting of consecutive and/or competing intra-complex hydride abstraction and
      proton transfer, intraannular proton shifts (H+ ring walk) and interannular
      proton transfer, hydrogen exchange ("scrambling") processes, and cyclisation and
      other electrophilic substitution reactions, is of general importance in this
      field of gas-phase ion chemistry, and more recent examples concerning protonated
      ethers, benzylpyridinium and benzylammmonium ions are discussed in which these
      recurring features play central and concerted mechanistic roles as well.

PMID- 22641719
TI  - Catalysis in hydrogen-bridged radical cations.
AB  - Hydrogen-bridged radical cations (HBRCs) are an intriguing subclass of ion
      molecule complexes. They may act as key intermediates of remarkable stability in
      both association and dissociation reactions of heteroatom-containing molecular
      ions. The H-bridge of such an HBRC can promote isomerization of its ionic
      component by H-transfer. Proton-transport catalysis (PTC) is a prime example.
      Here, a neutral molecule promotes the smooth transformation of an ion into its H
      shift isomer by consecutive proton-transfer reactions. A celebrated case is the
      water catalyzed isomerization of CH(3)OH(*+) into its more stable distonic isomer
      (*)CH(2)OH(2)(+). Other early studies of  PTC also deal with catalyzing 1,2-H
      shifts in association reactions. This short review focuses on more recent
      combined experimental and computational studies of catalysis in HBRCs. Mechanisms
      involving both proton and H atom transfers have been proposed for a variety of
      systems of H-shift isomers.  It has also become clear that PTC is not confined to
      bimolecular reactions. It also features in the unimolecular chemistry of
      heteroatom- containing ions, which have a tendency to isomerize to HBRCs en route
      to their dissociation.

PMID- 22641720
TI  - Investigation on the role of pneumatic aspects in electrospray, desorption
      electrospray surface ionization and surface activated chemical ionization.
AB  - This review reports the results of some studies carried out by us on the role of
      pneumatic aspects in electrospray and desorption electrospray surface ionization,
      with the aim to propose some relevant aspects of the mechanisms involved in these
      ionization methods. Electrospray ion sources, with the exception of the nano-
      electrospray source, operate with the concurrent action of a strong electrical
      field and a supplementary coaxial gas flow. The electrical field is responsible
      for electrospraying of the analyte solution but the use of a coaxial gas flow
      leads to a significant increase of the analyte signal and allows the use of
      higher solution flows. However, by employing capillary voltages much lower than
      those necessary to activate the electrospray phenomenon, analyte ions are still
      observed and this indicates that different mechanisms must be operative for ion
      production. Under these conditions, ion generation could take place from the
      neutral pneumatically sprayed droplet by field-induced droplet ionization. Also
      in the case of desorption electrospray ionization (DESI), and without any voltage
      on the spraying capillary as well as on the surface of interest, ions of 
      analytes present on the surface become detectable and this shows that
      desorption/ionization of analytes occurs  by neutral droplets impinging the
      surface. Consequently, the pneumatic effect of the impinging droplets plays a
      relevant role, and for these reasons the method has been called pneumatic
      assisted desorption (PAD). Some analogies existing between PAD and surface
      activated chemical ionization (SACI), based on the insertion of a metallic
      surface inside an atmospheric pressure chemical ionization source operating
      without corona discharge,  are discussed.

PMID- 22641721
TI  - The applicability of the kinetic method for measuring relative affinities of
      macromolecules for polyatomic substrates.
AB  - This paper is a review of the kinetic method for the determination of
      thermochemical values for gas-phase molecules. In addition, we have explored the
      utility of the kinetic method to obtain meaningful relative binding energies of
      macromolecules for polyatomic substrates using a system comprising
      poly(methylmethacrylate) (PMMA) oligomers and doubly protonated diaminoalkanes.
      The major factors which determined the suitability of the kinetic method for this
      system were identified as (i) the structural arrangement of the parent ion
      complex, (ii) possible reverse activation barriers, and (iii) the evaluations of
      Delta(DeltaS?). Molecular mechanics/molecular dynamics (MM/MD) simulations,
      together with ion mobility spectrometry, suggests the parent ion complexes
      represent a relatively equal sharing of the substrate between two the PMMA
      oligomers within the complex and that the two PMMA oligomers interact almost
      exclusively with the substrate, and not with each other. MS/MS of the trimeric
      parent complexes resulted in one PMMA unit leaving as a neutral which suggests
      very limited coulombic repulsion (that would contribute to a reverse activation
      barrier). The drift times of PMMA-diaminoalkane complexes that were generated
      directly by ESI-MS or by dissociation of a trimeric PMMA-diaminoalkane-PMMA
      complex were found to be identical, and when combined with MM/MD simulations
      suggested that the product PMMA-diaminoalkane dication has the same conformation
      as it does when part of a trimeric complex. This is evidence for Delta(DeltaS?) ?
      Delta(DeltaS) and using a statistical mechanics approach, Delta(DeltaS) ? 0. The
      effective temperature variable in the kinetic method expression was found to
      decrease as a function of the size of the trimeric complex, suggesting that the
      population distribution of the dissociating ensemble of complexes narrows as size
      increases.

PMID- 22641722
TI  - Johan Klaas Terlouw, scientist.

PMID- 22641723
TI  - Laser-induced acoustic desorption (LIAD) mass spectrometry.
AB  - Large thermally labile molecules were not amenable to mass spectrometric analysis
      until the development of atmospheric pressure evaporation/ionization methods,
      such as electrospray ionization (ESI) and matrix-assisted laser
      desorption/ionization (MALDI), since attempts to evaporate these molecules by
      heating induces degradation of the sample. While ESI and MALDI are relatively
      soft desorption/ionization techniques, they are both limited to preferential
      ionization of acidic and basic analytes. This limitation has been the driving
      force for the development of other soft desorption/ionization techniques. One
      such method employs laser-induced acoustic desorption (LIAD) to evaporate neutral
      sample molecules into mass spectrometers. LIAD utilizes acoustic waves generated
      by a laser pulse in a thin metal foil. The acoustic waves travel through the foil
      and cause desorption of neutral molecules that have been deposited on the
      opposite side of the foil. One of the advantages of LIAD is that it desorbs low
      energy molecules that can be ionized by a variety of methods, thus allowing the
      analysis of large molecules that are not amenable to ESI and MALDI. This review
      covers the generation of acoustic waves in foils via a laser pulse, the
      parameters affecting the generation of acoustic waves, possible mechanisms for
      desorption of neutral molecules, as well as the various uses of LIAD by mass
      spectrometrists. The conditions used to generate acoustic or stress waves in
      solid materials  consist of three regimes: thermal, ablative, and constrained.
      Each regime is discussed, in addition to the mechanisms that lead to the ablation
      of the metal from the foil and generation of acoustic waves for two of the
      regimes. Previously proposed desorption mechanisms for LIAD are presented along
      with the flaws associated with some of them. Various experimental parameters,
      such as the exact characteristics of the laser pulse and foil used, are
      discussed. The internal and kinetic energy of the neutral desorbed molecules are
      also considered.  Our research group has been instrumental in the development and
      use of LIAD. For example, we have systematically examined the influence of many
      parameters, such as the type of the foil and its thickness, as well  as the
      analyte layer's thickness, on the efficiency of desorption of neutral molecules.
      The coupling of LIAD with different instruments and ionization techniques allows
      for broad use of LIAD in our research laboratories. The most important
      applications involve analytes that cannot be analyzed by using other mass
      spectrometric methods, such as large saturated hydrocarbons and heavy hydrocarbon
      fractions of petroleum. We  also use LIAD to characterize lipids, peptides, and
      oligonucleotides. Fundamental research on the reactions of charged mono-, bi-,
      and polyradicals with biopolymers, especially oligonucleotides,  also requires
      the use of LIAD, as well as thermochemical measurements for neutral biopolymers.
      These are but a few of the uses of LIAD in our research group.

PMID- 22641724
TI  - Interfacing multistage mass spectrometry with liquid chromatography or ion
      mobility separation for synthetic polymer analysis.
AB  - Synthetic polymers are naturally mixtures of homologs, even in pure form. More
      complexity is introduced by the presence of different comonomers, end groups
      and/or macromolecular architectures. The analysis of such systems is
      substantially facilitated by interfacing mass spectrometry (MS), which disperses
      based  on mass, with an additional level of separation involving either
      interactive liquid chromatography (LC) or ion mobility (IM) spectrometry, both of
      which are readily coupled online with electrospray ionization and MS detection.
      IM-MS separates in the gas phase, post-ionization and, therefore, is ideally
      suitable for labile and reactive polymers. Its usefulness is illustrated with the
      characterization of non-covalent siloxane-saccharide complexes,
      metallosupramolecular assemblies and an air- and moisture-sensitive inorganic
      polymer, poly(dichlorophosphazene). Conversely, LC-MS which separates in solution
      phase, before ionization, is most effective for the analysis of polymeric
      mixtures whose components differ in polarity. Interactive LC conditions can be
      optimized to disperse by the content of hydrophobic units, as is demonstrated for
      amphiphilic polyether copolymers and sugar-based nonionic surfactant blends. Both
      LC-MS and IM-MS can be extended into a third dimension by tandem mass
      spectrometry (MS(2)) studies on select oligomers, in order to obtain insight into
      individual end groups and isomeric architectures, comonomer sequences and degree
      of substitution, for example, by hydrophobic functionalities.

PMID- 22641725
TI  - Energy partitioning in single-electron transfer events between gaseous dications
      and their neutral counterparts.
AB  - Electron-transfer reactions between hydrocarbon dications and neutral
      hydrocarbons lead to an unequal deposition of the excess energy from the reaction
      in the pair of monocations formed. The initial observation of this phenomenon was
      explained by the different states accessible upon single-electron capture by a
      dication compared to single-electron ejection from a neutral compound.
      Alternatively, however, isomeric structures of the dicationic species, pronounced
      Franck-Condon effects, as well as excess energy in the dicationic precursors
      could cause the asymmetric energy partitioning in such dication/neutral
      collisions. Here, the investigation of this phenomenon in an interdisciplinary
      cooperation is described, shedding light not only upon a possible solution of the
      problem at hand, but also providing an example for the synergistic benefits of
      international research networks applying complementary approaches.

PMID- 22641726
TI  - Time-resolved mass spectrometry for monitoring millisecond time-scale solution
      phase processes.
AB  - Many chemical and biochemical reactions equilibrate within a few seconds of
      initiation under "native" conditions. To understand the microscopic processes
      underlying these reactions, the most direct approach is to monitor the reaction
      as equilibrium is established (i.e. the reaction kinetics). However, this
      requires the ability to characterize the reaction mixture on the millisecond time
      scale. In this review, we survey the contributions of time-resolved mass
      spectrometry (TR-MS) to the characterization of millisecond time-scale
      (bio)chemical processes, with a focus on biochemical applications. Compared to
      conventional time-resolved techniques, which use optical detection, the primary
      advantage of TR-MS is the ability to detect virtually all reactive species
      simultaneously. This provides a singularly high detail account of the reaction
      without the need for a chromophoric change on turnover or artificial chromophoric
      probes. To provide millisecond time-resolution, TR-MS set-ups usually employ
      continuous-flow rapid mixers, corresponding  either to a fixed "tee" that
      provides a single reaction time-point or an adjustable position mixer that allows
      continuous reaction monitoring. TR-MS has been used to monitor processes with
      rates up to 500 s(-1) and to provide a detailed account of complex reactions
      involving 10 co- populated species. This corresponds to significantly lower time
      resolution than optical methods, which can measure rates in excess of 900 s(-1)
      under ideal conditions, but substantially more detail (optical studies are
      typically limited to one or two analytes). TR-MS has been implemented on a number
      of platforms, including capillary and microfluidic set-ups. Capillary-based
      implementations are straightforward to fabricate and provide the most efficient
      rapid mixing. Microfluidic implementations have also been devised to enable multi
      step experimental workflows that incorporate TR-MS. As a general method for time
      resolved measurements, the applications for TR-MS are wide ranging. TR-MS has
      been used to identify intermediates in  organic reactions, reveal protein
      (un)folding mechanisms, monitor enzyme catalysis in the pre-steady-state and, in
      conjunction with hydrogen-deuterium exchange, characterize protein conformational
      dynamics. While not without limitations, TR-MS represents a powerful alternative
      for measuring solution phase processes on the millisecond time-scale and a new,
      promising approach for revealing mechanistic details in (bio)chemical reactions.

PMID- 22641727
TI  - Proton mobility in water clusters.
AB  - Proton mobility in water occurs quickly according to the so-called Grotthuss
      mechanism. This process and its elementary reaction steps can be studied in great
      detail by applying suitable mass spectrometric methods to ionic water clusters.
      Careful choice of suitable core ions in combination with analysis of cluster size
      trends in hydrogen/deuterium isotope exchange rates allows for detailed insights
      into fascinating dynamical systems. Analysis of the experiments has been promoted
      by extensive and systematic quantum chemical model  calculations. Detailed low
      energy mechanistic pathways for efficient water rearrangement and proton transfer
      steps, in particular cases along short preformed "wires" of hydrogen bonds, have
      been identified in consistency with experimental findings.

PMID- 22641728
TI  - Structures and physical properties of gaseous metal cationized biological ions.
AB  - Metal chelation can alter the activity of free biomolecules by modifying their
      structures or stabilizing higher energy tautomers. In recent years, mass
      spectrometric techniques have been used to investigate the effects of metal
      complexation with proteins, nucleobases and nucleotides, where small
      conformational changes  can have significant physiological consequences. In
      particular, infrared multiple photon dissociation spectroscopy has emerged as an
      important tool for determining the structure and reactivity of gas-phase ions.
      Unlike other mass spectrometric approaches, this method is able to directly
      resolve structural isomers using characteristic vibrational signatures. Other
      activation and dissociation methods, such as blackbody infrared radiative
      dissociation or collision-induced dissociation can also reveal information about
      the thermochemistry and dissociative pathways of these biological ions. This
      information can then be used to provide information about the structures of the
      ionic complexes under study. In this article, we review the use of gas-phase
      techniques in characterizing metal-bound biomolecules. Particular attention will
      be given to our own contributions, which detail the ability of metal cations to
      disrupt nucleobase pairs, direct the self-assembly of nucleobase clusters and
      stabilize non-canonical isomers of amino acids.

PMID- 22641729
TI  - Mass spectrometry-based structural proteomics.
AB  - Structural proteomics is the application of protein chemistry and modern mass
      spectrometric techniques to problems such as the characterization of protein
      structures and assemblies and the detailed determination of protein-protein
      interactions. The techniques used in structural proteomics include crosslinking,
      photoaffinity labeling, limited proteolysis, chemical protein modification and
      hydrogen/deuterium exchange, all followed by mass spectrometric analysis. None of
      these methods alone can provide complete structural information, but a
      "combination" of these complementary approaches can be used to provide enough
      information for answering important biological questions. Structural proteomics
      can help to determine, for example, the detailed structure of the interfaces
      between proteins that may be important drug targets and the interactions between
      proteins and ligands. In this review, we have tried to provide a brief overview
      of structural proteomics methodologies, illustrated with examples from our
      laboratory and from the literature.

PMID- 22641731
TI  - Re-examination of the role of peritoneal dialysis to treat patients with acute
      kidney injury.

PMID- 22641732
TI  - Peritoneal dialysis in acute kidney injury: Brazilian experience.

PMID- 22641734
TI  - The international Vicenza course on peritoneal dialysis--30-year anniversary.

PMID- 22641733
TI  - Trials (and tribulations) of biocompatible peritoneal dialysis fluids.

PMID- 22641735
TI  - Peritoneal dialysis in Cape Town, South Africa.
AB  - BACKGROUND: Chronic kidney disease is a major public health problem in sub
      Saharan Africa (SSA), which encompasses 70% of the least-developed countries in
      the world. Most people in SSA have no access to any form of renal replacement
      therapy (RRT). Given its ease of performance and patient independence, peritoneal
      dialysis (PD) should be an ideal form of RRT in SSA, but several complex and
      interdependent factors make PD a difficult option in SSA. The present review
      describes the practice of PD in SSA, with emphasis on Cape Town, South Africa.
      METHODS AND RESULTS: After a review of the recent PubMed literature on RRT in SSA
      and an appraisal of nephrology practice in South Africa, factors that make the
      provision of RRT (especially PD) a challenge in SSA include the low number of
      qualified health care workers, socio-demographic issues (poor housing,
      electricity, and water supplies), and the cost of PD fluids in the region.
      Although South Africa has the largest PD population in all of SSA, the growth of
      PD in South Africa is specifically impeded by the system of RRT rationing, which
      favors HD; the methods of funding for dialysis and for remuneration of doctors in
      private practice; and many other socio-economic factors. The peritonitis rate
      remains relatively high, and it is a significant contributor to morbidity in PD
      patients in Cape Town. CONCLUSIONS: In many parts of SSA, PD could be the main
      dialysis modality. However, African governments must start taking responsibility
      for their people by providing adequate funds for renal replacement programs.
      Attempts to produce PD fluids locally and to train and educate health care
      workers will greatly improve the use of PD as a RRT option in SSA.

PMID- 22641736
TI  - Outcome of acute peritoneal dialysis in northern Tanzania.
AB  - Data on the burden of acute kidney injury (AKI) in resource-poor countries such
      as Tanzania are minimal because of a lack of nephrology services and an inability
      to recognize and diagnose AKI with any certainty. In the few published studies,
      high morbidity and mortality are reported. Improved nephrology care and dialysis
      may lower the mortality from AKI in these settings. Hemodialysis is expensive and
      technically challenging in resource-limited settings. The technical simplicity of
      peritoneal dialysis and the potential to reduce costs if consumables can be made
      locally, present an opportunity to establish cost-effective programs for managing
      AKI. Here, we document patient outcomes in a pilot peritoneal dialysis program
      established in 2009 at a referral hospital in Northern Tanzania.

PMID- 22641737
TI  - Gentamicin-resistant infections in peritoneal dialysis patients using topical
      gentamicin exit-site prophylaxis: a report of two cases.

PMID- 22641738
TI  - Relapsing Brevibacterium casei peritonitis: value of 16S rRNA gene sequencing in
      accurate species identification.

PMID- 22641739
TI  - Gordona: a rare cause of peritoneal dialysis peritonitis.

PMID- 22641740
TI  - Impact of the inclusion of a nephrologist on the surgical team for peritoneal
      catheter insertion.

PMID- 22641741
TI  - Renalase in peritoneal dialysis patients is not related to blood pressure, but to
      dialysis vintage.

PMID- 22641742
TI  - Acute kidney injury: are we biased against peritoneal dialysis?

PMID- 22641743
TI  - Accidental placement of a peritoneal dialysis catheter in the Retzius space: two
      case reports.

PMID- 22641744
TI  - Preoperative peritoneal scintigraphy.

PMID- 22641745
TI  - Unusual cause of late peritoneal dialysate leakage.

PMID- 22641746
TI  - Management of pericannular bleeding after peritoneal dialysis catheter placement.

PMID- 22641748
TI  - Pasteurella multocida peritonitis with bacteremia on initiation of peritoneal
      dialysis.

PMID- 22641747
TI  - Continuous ambulatory peritoneal dialysis-related exit-site infections caused by
      Achromobacter denitrificans and A. xylosoxidans.

PMID- 22641749
TI  - Paecilomyces lilacinus peritonitis in a peritoneal dialysis patient.

PMID- 22641750
TI  - Intermittent intraperitoneal dose of teicoplanin in peritoneal dialysis-related
      peritonitis.

PMID- 22641752
TI  - How children with specific language impairment view social situations: an eye
      tracking study.
AB  - OBJECTIVE: Children with specific language impairment (SLI) face risks for social
      difficulties. However, the nature and developmental course of these difficulties
      remain unclear. Gaze behaviors have been studied by using eye tracking among
      those with autism spectrum disorders (ASDs). Using this method, we compared the
      gaze behaviors of children with SLI with those of individuals with ASD and
      typically developing (TD) children to explore the social perception of children
      with SLI. METHODS: The eye gazes of 66 children (16 with SLI, 25 with ASD, and 25
      TD) were studied while viewing videos of social interactions. Gaze behaviors were
      summarized with multidimensional scaling, and participants with similar gaze
      behaviors were represented proximally in a 2-dimensional plane. RESULTS: The SLI
      and TD groups each formed a cluster near the center of the multidimensional
      scaling plane, whereas the ASD group was distributed around the periphery. Frame
      by-frame analyses showed that children with SLI and TD children viewed faces in a
      manner consistent with the story line, but children with ASD devoted less
      attention to faces and social interactions. During speech scenes, children with
      SLI were significantly more fixated on the mouth, whereas TD children viewed the
      eyes and the mouth. CONCLUSIONS: Children with SLI viewed social situations in
      ways similar to those of TD children but different from those of children with
      ASD. However, children with SLI concentrated on the speaker's mouth, possibly to
      compensate for audiovisual processing deficits. Because eyes carry important
      information, this difference may influence the social development of children
      with SLI.

PMID- 22641753
TI  - Meta-analysis of long-chain polyunsaturated fatty acid supplementation of formula
      and infant cognition.
AB  - BACKGROUND AND OBJECTIVE: Infant formula is supplemented with long-chain
      polyunsaturated fatty acids (LCPUFAs) because they are hypothesized to improve
      cognition. Several randomized controlled clinical trials have examined the effect
      of LCPUFA supplementation of infant formula on cognitive development. We
      conducted this meta-analysis to examine the efficacy of LCPUFA supplementation of
      infant formula on early cognitive development. METHODS: Two authors searched
      PubMed, PsychInfo, and Scopus for randomized controlled clinical trials assessing
      the efficacy of LCPUFA supplementation of infant formulas on cognition. Our
      analysis was restricted to randomized controlled clinical trials that examined
      the effect of LCPUFA supplementation on infant cognition using Bayley Scales of
      Infant Development. Our primary outcome was the weighted mean difference in
      Bayley Scales of Infant Development score between infants fed formula
      supplemented with LCPUFA compared with unsupplemented formula. We conducted
      secondary subgroup analyses and meta-regression to examine the effects of study
      sample, LCPUFA dose, and trial methodologic quality on measured efficacy of
      supplementation. RESULTS: Twelve trials involving 1802 infants met our inclusion
      criteria. Our meta-analysis demonstrated no significant effect of LCPUFA
      supplementation of formula on infant cognition. There was no significant
      heterogeneity or publication bias between trials. Secondary analysis failed to
      show any significant effect of LCPUFA dosing or prematurity status on
      supplementation efficacy. CONCLUSIONS: LCPUFA supplementation of infant formulas
      failed to show any significant effect on improving early infant cognition.
      Further research is needed to determine if LCPUFA supplementation of infant
      formula has benefits for later cognitive development or other measures of
      neurodevelopment.

PMID- 22641754
TI  - Developmental status of 1-year-old infants fed breast milk, cow's milk formula,
      or soy formula.
AB  - BACKGROUND AND OBJECTIVE: Although soy formula has been reported to support
      normal development, concerns exist regarding potential adverse developmental
      effects of phytochemicals associated with soy protein. This study characterized
      developmental status (mental, motor, and language) of breastfed (BF), milk-based
      formula-fed (MF), or soy protein-based formula-fed (SF) infants during the first
      year of life. METHODS: Healthy infants (N = 391) were assessed longitudinally at
      ages 3, 6, 9, and 12 months. Development was evaluated by using the Bayley Scales
      of Infant Development and the Preschool Language Scale-3. Mixed effects models
      were used while adjusting for socioeconomic status, mother's age and IQ,
      gestational age, gender, birth weight, head circumference, race, age, and diet
      history. RESULTS: No differences were found between formula-fed infants (MF
      versus SF). BF infants scored slightly higher than formula-fed infants on the
      Mental Developmental Index (MDI) score at ages 6 and 12 months (P < .05). Infants
      who were breastfed also had higher Psychomotor Development Index scores than SF
      infants at age 6 months and slightly higher Preschool Language Scale-3 scores
      than MF infants at ages 3 and 6 months (P < .05). In addition, BF infants had a
      lower probability to score within the lower MDI quartile compared with MF infants
      and a higher likelihood to score within the upper quartile for the MDI and
      Psychomotor Development Index compared with SF infants. CONCLUSIONS: This unique
      study showed that all scores on developmental testing were within established
      normal ranges and that MF and SF groups did not differ significantly.
      Furthermore, this study demonstrated a slight advantage of BF infants on
      cognitive development compared with formula-fed infants.

PMID- 22641755
TI  - The distribution of physical activity in an after-school friendship network.
AB  - OBJECTIVE: To examine whether a child's friendship network in an afterschool
      program influences his/her physical activity. METHODS: Three waves of data were
      collected from school-aged children participating in aftercare (n = 81; mean [SD]
      age, 7.96 [1.74] years; 40% African American, 39% white, and 19% Latino) a name
      generator survey was used to map each child's social network, and accelerometers
      were used to measure physical activity. We applied stochastic actor-based
      modeling for social networks and behavior. RESULTS: Children did not form or
      dissolve friendships based on physical activity levels, but existing friendships
      heavily influenced children's level of physical activity. The strongest influence
      on the amount of time children spent in moderate-to-vigorous activity in the
      afterschool hours was the activity level of their immediate friends. Children
      consistently made adjustments to their activity levels of 10% or more to emulate
      the activity levels of their peers (odds ratio [OR] = 6.89, P < .01). Age (OR =
      0.92, P < .10) and obesity status (OR = 0.66, P < .10) had marginally significant
      and relatively small direct effects on the activity. Gender had no direct effect
      on activity. CONCLUSIONS: These results suggest that friendship ties play a
      critical role in setting physical activity patterns in children as young as 5 to
      12 years. Children's activity levels can be increased, decreased, or stabilized
      depending on the activity level of their immediate social network during a 12
      week afterschool program. Network-based interventions hold the potential to
      produce clinically significant changes to children's physical activity.

PMID- 22641756
TI  - Is the measure the message: the BSID and nutritional interventions.

PMID- 22641757
TI  - A 4-year exercise program in children increases bone mass without increasing
      fracture risk.
AB  - BACKGROUND: Most prospective pediatric exercise intervention studies cover <1
      year and use bone traits as surrogate end points for fractures. This prospective
      controlled exercise intervention study therefore followed not only skeletal
      development but also fracture incidence for 4 years. METHODS: Fractures were
      prospectively registered in a cohort of children aged 7 to 9 years, 446 boys and
      362 girls in the intervention group (2675 person-years) and 807 boys and 780
      girls in the control group (5661 person-years). The intervention included 40
      minutes per day of school physical education for 4 years whereas the controls had
      60 minutes per week. In a subsample, 73 boys and 48 girls in the intervention and
      52 boys and 48 girls in the control group, bone mineral content (g) and bone
      width (cm) were followed by means of dual-energy radiograph absorptiometry.
      RESULTS: The rate ratio for fractures was 1.11. In the dual-energy radiograph
      absorptiometry-measured children, there were no group differences at baseline in
      age, anthropometrics, or bone traits. The mean annual gain in lumbar spine bone
      mineral content was 7.0% higher in girls and 3.3% higher in boys and in femoral
      neck width 1.7% higher in girls and 0.6% higher in boys in the intervention than
      in the control group. CONCLUSIONS: A population-based moderately intense 4-year
      exercise program in 7- to 9-year-old children increased bone mass and size
      without affecting the fracture risk.

PMID- 22641758
TI  - Off-label use of recombinant factor VIIa in pediatric patients.
AB  - OBJECTIVE: To examine off-label recombinant factor VIIa (rFVIIa) use in pediatric
      patients including clinical indications, dose, adverse events, and outcomes.
      METHODS: All pediatric patients entered into the Haemostasis Registry from 75
      participating hospitals were analyzed. RESULTS: Three hundred and eighty-eight
      pediatric patients received off-label rFVIIa from 2003 to 2009. Median age was 12
      months (interquartile range 1 month to 11 years). Clinical context included
      cardiac surgery (52.1%), medical (11.6%), other surgery (10.8%),
      hematology/oncology (10.3%), trauma (9.3%), intracranial hemorrhage (3.1%), and
      liver disease (2.8%). Twenty-six patients received extracorporeal membrane
      oxygenation at the time of rFVIIa administration. Median first dose was 114
      MUg/kg (interquartile range 90-181; range 7-2250). Thirty-four percent received
      >1 dose. There was a reduction in usage of red blood cells, platelets, fresh
      frozen plasma, and cryoprecipitate in the 24 hours after the first dose for all
      patients (all P values < .001). Thromboembolic adverse events (TEAs) were
      reported in 5.4%. No association between TEA and size of first dose was found.
      Where data were available, 82% of patients were subjectively classified as
      responding to rFVIIa. Overall 28-day mortality was 27%. In multivariate analysis,
      pH values before administration and clinical context were independently
      associated with response to first dose and 28-day mortality. CONCLUSIONS: There
      was a significant reduction in blood product administration after rFVIIa and a
      subjective response rate of 82%. Both pH and clinical context were associated
      with response to rFVIIa and mortality. Overall, 5.4% had a TEA reported.

PMID- 22641759
TI  - Pediatricians, schools, and media.

PMID- 22641760
TI  - Clot dissolution: a novel treatment of midgut volvulus.
AB  - Midgut volvulus due to malrotation may result in loss of the small bowel. Until
      now, after derotation of the volvulus, pediatric surgeons do not deal with the
      mesenteric thrombosis, which causes continuing ischemia of the intestine. On
      occasion, a "second look" laparotomy is performed in the hope that some
      improvement in blood supply to the intestine has occurred. We describe a new
      combined treatment to restore intestinal perfusion based on digital massage of
      the superior mesenteric vessels after derotation and systemic infusion of tissue
      type plasminogen activator. This new therapy has been successful in 2 neonates
      with severe intestinal ischemia due to volvulus.

PMID- 22641762
TI  - Treatment of maladaptive aggression in youth: CERT guidelines I. Engagement,
      assessment, and management.
AB  - OBJECTIVE: To develop guidelines for management and treatment of maladaptive
      aggression in the areas of family engagement, assessment and diagnosis, and
      initial management, appropriate for use by primary care clinicians and mental
      health providers. Maladaptive aggression in youth is increasingly treated with
      psychotropic medications, particularly second-generation antipsychotic agents.
      Multiple treatment modalities are available, but guidance for clinicians'
      assessment and treatment strategies has been inadequately developed. To address
      this need, the Center for Education and Research on Mental Health Therapeutics
      and the REACH Institute convened a steering group of national experts to develop
      evidence-based treatment recommendations for maladaptive aggression in youth.
      METHODS: Evidence was assembled and evaluated in a multistep process that
      included a systematic review of published literature; a survey of experts on
      recommended treatment practices; a consensus conference that brought together
      clinical experts along with researchers, policy makers, and family advocates; and
      subsequent review and discussion by the steering committee of successive drafts
      of the recommendations. The Center for Education and Research on Mental Health
      Therapeutics Treatment of Maladaptive Aggression in Youth (T-MAY) guidelines
      reflect a synthesis of the available evidence, based on this multistep process.
      RESULTS: The current article describes 9 recommendations for family engagement,
      assessment, and diagnosis as key prerequisites for treatment selection and
      initiation. CONCLUSIONS: Recognizing the family and social context in which
      aggressive symptoms arise, and understanding the underlying psychiatric
      conditions that may be associated with aggression, are essential to treatment
      planning.

PMID- 22641763
TI  - Treatment of maladaptive aggression in youth: CERT guidelines II. Treatments and
      ongoing management.
AB  - OBJECTIVE: To develop guidelines for management and treatment of maladaptive
      aggression in youth in the areas of psychosocial interventions, medication
      treatments, and side-effect management. METHODS: Evidence was assembled and
      evaluated in a multistep process, including systematic reviews of published
      literature; an expert survey of recommended practices; a consensus conference of
      researchers, policymakers, clinicians, and family advocates; and review by the
      steering committee of successive drafts of the recommendations. The Center for
      Education and Research on Mental Health Therapeutics Treatment of Maladaptive
      Aggression in Youth guidelines reflect a synthesis of the available evidence,
      based on this multistep process. RESULTS: This article describes the content,
      rationale, and evidence for 11 recommendations. Key treatment principles include
      considering psychosocial interventions, such as evidence-based parent and child
      skills training as the first line of treatment; targeting the underlying disorder
      first following evidence-based guidelines; considering individual psychosocial
      and medical factors, including cardiovascular risk in the selection of agents if
      medication treatment (ideally with the best evidence base) is initiated; avoiding
      the use of multiple psychotropic medications simultaneously; and careful
      monitoring of treatment response, by using structured rating scales, as well as
      close medical monitoring for side effects, including metabolic changes.
      CONCLUSIONS: Treatment of children with maladaptive aggression is a "moving
      target" requiring ongoing assimilation of new evidence as it emerges. Based on
      the existing evidence, the Treatment of Maladaptive Aggression in Youth
      guidelines provide a framework for management of maladaptive aggression in youth,
      appropriate for use by primary care clinicians and mental health providers.

PMID- 22641764
TI  - Neonatal apneic seizure of occipital lobe origin: continuous video-EEG recording.
AB  - We present 2 term newborn infants with apneic seizure originating in the
      occipital lobe that was diagnosed by video-EEG. One infant had ischemic
      infarction in the distribution of the posterior cerebral artery, extending to the
      cingulate gyrus. In the other infant, only transient occipital hyperechogenicity
      was observed by using neurosonography. In both cases, although the critical EEG
      discharge was observed at the occipital level, the infants presented no clinical
      manifestations. In patient 1, the discharge extended to the temporal lobe first,
      with subtle motor manifestations and tachycardia, then synchronously to both
      hemispheres (with bradypnea/hypopnea), and the background EEG activity became
      suppressed, at which point the infant experienced apnea. In patient 2, background
      EEG activity became suppressed right at the end of the focal discharge,
      coinciding with the appearance of apnea. In neither case did the clinical
      description by observers coincide with video-EEG findings. The existence of
      connections between the posterior limbic cortex and the temporal lobe and
      midbrain respiratory centers may explain the clinical symptoms recorded in these
      2 cases. The novel features reported here include video-EEG capture of apneic
      seizure, ischemic lesion in the territory of the posterior cerebral artery as the
      cause of apneic seizure, and the appearance of apnea when the epileptiform ictal
      discharge extended to other cerebral areas or when EEG activity became
      suppressed. To date, none of these clinical findings have been previously
      reported. We believe this pathology may in fact be fairly common, but that video
      EEG monitoring is essential for diagnosis.

PMID- 22641761
TI  - Approach to infants born at 22 to 24 weeks' gestation: relationship to outcomes
      of more-mature infants.
AB  - OBJECTIVE: We sought to determine if a center's approach to care of premature
      infants at the youngest gestational ages (22-24 weeks' gestation) is associated
      with clinical outcomes among infants of older gestational ages (25-27 weeks'
      gestation). METHODS: Inborn infants of 401 to 1000 g birth weight and 22 0/7 to
      27 6/7 weeks' gestation at birth from 2002 to 2008 were enrolled into a
      prospectively collected database at 20 centers participating in the Eunice
      Kennedy Shriver National Institute of Child Health and Human Development Neonatal
      Research Network. Markers of an aggressive approach to care for 22- to 24-week
      infants included use of antenatal corticosteroids, cesarean delivery, and
      resuscitation. The primary outcome was death before postnatal day 120 for infants
      of 25 to 27 weeks' gestation. Secondary outcomes were the combined outcomes of
      death or a number of morbidities associated with prematurity. RESULTS: Our study
      included 3631 infants 22 to 24 weeks' gestation and 5227 infants 25 to 27 weeks'
      gestation. Among the 22- to 24-week infants, use of antenatal corticosteroids
      ranged from 28% to 100%, cesarean delivery from 13% to 65%, and resuscitation
      from 30% to 100% by center. Centers with higher rates of antenatal corticosteroid
      use in 22- to 24-week infants had reduced rates of death, death or retinopathy of
      prematurity, death or late-onset sepsis, death or necrotizing enterocolitis, and
      death or neurodevelopmental impairment in 25- to 27-week infants. CONCLUSIONS:
      This study suggests that physicians' willingness to provide care to extremely low
      gestation infants as measured by frequency of use of antenatal corticosteroids is
      associated with improved outcomes for more-mature infants.

PMID- 22641765
TI  - Sensory integration therapies for children with developmental and behavioral
      disorders.
AB  - Sensory-based therapies are increasingly used by occupational therapists and
      sometimes by other types of therapists in treatment of children with
      developmental and behavioral disorders. Sensory-based therapies involve
      activities that are believed to organize the sensory system by providing
      vestibular, proprioceptive, auditory, and tactile inputs. Brushes, swings, balls,
      and other specially designed therapeutic or recreational equipment are used to
      provide these inputs. However, it is unclear whether children who present with
      sensory-based problems have an actual "disorder" of the sensory pathways of the
      brain or whether these deficits are characteristics associated with other
      developmental and behavioral disorders. Because there is no universally accepted
      framework for diagnosis, sensory processing disorder generally should not be
      diagnosed. Other developmental and behavioral disorders must always be
      considered, and a thorough evaluation should be completed. Difficulty tolerating
      or processing sensory information is a characteristic that may be seen in many
      developmental behavioral disorders, including autism spectrum disorders,
      attention-deficit/hyperactivity disorder, developmental coordination disorders,
      and childhood anxiety disorders. Occupational therapy with the use of sensory
      based therapies may be acceptable as one of the components of a comprehensive
      treatment plan. However, parents should be informed that the amount of research
      regarding the effectiveness of sensory integration therapy is limited and
      inconclusive. Important roles for pediatricians and other clinicians may include
      discussing these limitations with parents, talking with families about a trial
      period of sensory integration therapy, and teaching families how to evaluate the
      effectiveness of a therapy.

PMID- 22641766
TI  - Infective endocarditis causing ulnar mycotic aneurysm and compartment syndrome.

PMID- 22641768
TI  - An interesting cause of a swollen lower limb.

PMID- 22641767
TI  - Benedictine hand of 'central' origin.

PMID- 22641769
TI  - Regulation of mitochondrial DNA accumulation during oocyte growth and meiotic
      maturation in the mouse.
AB  - Oocytes accumulate an enormous quantity of mitochondrial (mt) DNA, and an
      insufficient amount of mtDNA may underlie some cases of poor oocyte quality
      leading to infertility. Little is known, however, about the mechanisms that
      govern the timing and regulation of mtDNA accumulation during oogenesis. We
      report, through analysis of the mtDNA content of individual oocytes of the mouse,
      that mtDNA accumulates steadily during oocyte growth to reach a value of ~175 000
      copies per cell. MtDNA content ceases to increase once oocytes reach full size
      and remains unchanged during meiotic maturation. To test whether mtDNA
      accumulation depends on oocyte growth, we inhibited growth in vitro in two ways -
      by exposing complexes comprising partially grown oocytes enclosed by granulosa
      cells to a chemical inhibitor of the phosphatidylinositol-3-kinase signaling
      pathway and by removing the surrounding granulosa cells from partially grown
      oocytes. Under both conditions, the oocytes fail to grow, but mtDNA accumulation
      is unaffected, indicating that the two processes can be mechanistically
      uncoupled. Quantitative analysis of the mRNAs encoding proteins required for
      mtDNA replication revealed that Polg (Polga) (polymerase-gamma, alpha-subunit),
      Polg2 (Polgb), and Tfam (transcription factor A, mitochondrial) increase during
      oocyte growth but then decrease after fully grown oocytes become
      transcriptionally silent as indicated by the non-surrounded nucleolus-to
      surrounded nucleolus transition. Thus, there is a correlation between the decline
      in the quantity of mRNAs encoding mtDNA replication factors in fully grown
      oocytes and the arrest of mtDNA accumulation in these cells, suggesting that the
      two events may be causally linked.

PMID- 22641770
TI  - Differential effects of testosterone and 17beta-estradiol on gonadal development
      in five anuran species.
AB  - Sex hormones are essential for sexual differentiation and play a key role in the
      development of gonads in amphibians. The goal of this study was to evaluate the
      influence of exogenous sex steroids, testosterone, and 17beta-estradiol (E(2)) on
      development of gonads in five anuran species differing in their evolutionary
      positions, sex determination, and mode of gonadogenesis. We found that in two
      closely related species of fire-bellied toad, Bombina bombina and Bombina
      variegata, testosterone and E(2) exposure results in sex reversal as well as
      intersex and undifferentiated gonads. Similarly, sex reversal was observed in
      Hyla arborea after exposure to male or female sex steroids. Xenopus laevis was
      sensitive to E(2) but only moderately to testosterone. In Bufo viridis, treatment
      with either sex hormone provoked a developmental delay in gonads and Bidder's
      organs. Therefore, susceptibility to hormonal sex reversal appeared species
      dependent but unrelated to genetic sex determination and the type of
      gonadogenesis. We also found that the onset of sex steroid exposure influences
      gonad differentiation and the meiotic status of the germ cells depends on their
      location within the gonad. Our findings reveal differential sensitivity of
      amphibians to testosterone and E(2), establishing a hierarchy of sensitivity to
      these hormones among different anuran species.

PMID- 22641772
TI  - Restricted processing of glycans by endomannosidase in mammalian cells.
AB  - Removal of alpha-glucose residues from nascent glycoproteins in the early
      secretory pathway is a requirement for further N-glycan maturation. Although
      deglucosylation is a stepwise process mediated by endoplasmic reticulum
      associated glucosidases I and II for most glycoproteins, Golgi endo-alpha
      mannosidase provides a backup mechanism for glycoprotein deglucosylation.
      Although conserved in mammals, in certain cell lines, endomannosidase activity in
      vitro appears to differ from its activity in cells following glucosidase
      inhibition. Here, we show that in bovine cells this is explained by restricted
      substrate specificity allowing processing of Glc(1)Man(7)GlcNAc(1/2) and
      Glc(1)Man(5)GlcNAc(1/2) but not fully glucosylated glycans that build up when
      glucosidases are inhibited. Our data further demonstrate that such specificity is
      determined genetically rather than post-translationally. We also demonstrate that
      the bovine endomannosidase is transcriptionally upregulated by comparison with
      glucosidase II in Madin-Darby bovine kidney cells and speculate that this is to
      compensate for the reduced catalytic activity as measured in the recombinant form
      of the enzyme.

PMID- 22641771
TI  - The C-terminal fragment of axon guidance molecule Slit3 binds heparin and
      neutralizes heparin's anticoagulant activity.
AB  - Slit3 is a large molecule with multiple domains and belongs to axon guidance
      families. To date, the biological functions of Slit3 are still largely unknown.
      Our recent study demonstrated that the N-terminal fragment of Slit3 is a novel
      angiogenic factor. In this study, we examined the biological function of the C
      terminal fragment of human Slit3 (HSCF). The HSCF showed a high-affinity binding
      to heparin. The binding appeared to be heparin/heparan sulfate-specific and
      depends on the size, the degree of sulfation, the presence of N- and 6-O-sulfates
      and carboxyl moiety of the polysaccharide. Functional studies observed that HSCF
      inhibited antithrombin binding to heparin and neutralized the antifactor IIa and
      Xa activities of heparin and the antifactor IIa activity of low-molecular-weight
      heparin (LMWH). Thromboelastography analysis observed that HSCF reversed
      heparin's anticoagulation in global plasma coagulation. Taken together, these
      observations demonstrate that HSCF is a novel heparin-binding protein that
      potently neutralizes heparin's anticoagulation activity. This study reveals a
      potential for HSCF to be developed as a new antidote to treat overdosing of both
      heparin and LMWH in clinical applications.

PMID- 22641773
TI  - The photovoltage of rods and cones in the dark-adapted mouse retina.
AB  - Research on photoreceptors has led to important insights into how light signals
      are detected and processed in the outer retina. Most information about
      photoreceptor function, however, comes from lower vertebrates. The large majority
      of mammalian studies are based on suction pipette recordings of outer segment
      currents, a technique that doesn't allow examination of phenomena occurring
      downstream of phototransduction. Only a small number of whole-cell recordings
      have been made, mainly in the macaque. Due to the growing importance of the mouse
      in vision research, we have optimized a retinal slice preparation that allows the
      reliable collection of perforated-patch recordings from light responding rods and
      cones. Unexpectedly, the frequency of cone recordings was much higher than their
      numeric proportion of ~3%. This allowed us to obtain direct functional evidence
      suggestive of rod-cone coupling in the mouse. Moreover, rods had considerably
      larger single photon responses than previously published for mammals (3.44 mV, SD
      1.37, n = 19 at 24 degrees C; 2.46 mV, SD 1.08, n = 10 at 36 degrees C), and a
      relatively high signal/noise ratio (6.4, SD 1.8 at 24 degrees C; 6.8, SD 2.8 at
      36 degrees C). Both findings imply a more favourable transmission at the rod-rod
      bipolar cell synapse. Accordingly, relatively few photoisomerizations were
      sufficient to elicit a half-maximal response (6.7, SD 2.7, n = 5 at 24 degrees C;
      10.6, SD 1.7, n = 3 at 36 degrees C), leading to a narrow linear response range.
      Our study demonstrates new features of mammalian photoreceptors and opens the way
      for further investigations into photoreceptor function using retinas from mutant
      mouse models.

PMID- 22641774
TI  - The Arabidopsis central vacuole as an expression system for intracellular
      transporters: functional characterization of the Cl-/H+ exchanger CLC-7.
AB  - Functional characterization of intracellular transporters is hampered by the
      inaccessibility of animal endomembranes to standard electrophysiological
      techniques. Here, we used Arabidopsis mesophyll protoplasts as a novel
      heterologous expression system for the lysosomal chloride-proton exchanger CLC-7
      from rat. Following transient expression of a rCLC-7:EGFP construct in isolated
      protoplasts, the fusion protein efficiently targeted to the membrane of the large
      central vacuole, the lytic compartment of plant cells. Membrane currents recorded
      from EGFP-positive vacuoles were almost voltage independent and showed time
      dependent activation at elevated positive membrane potentials as a hallmark. The
      shift in the reversal potential of the current induced by a decrease of cytosolic
      pH was compatible with a 2Cl(-)/1H(+) exchange stoichiometry. Mutating the so
      called gating glutamate into alanine (E245A) uncoupled chloride fluxes from the
      movement of protons, transforming the transporter into a chloride channel-like
      protein. Importantly, CLC-7 transport activity in the vacuolar expression system
      was recorded in the absence of the auxiliary subunit Ostm1, differently to recent
      data obtained in Xenopus oocytes using a CLC-7 mutant with partial plasma
      membrane expression. We also show that plasma membrane-targeted CLC-7(E245A) is
      non-functional in Xenopus oocytes when expressed without Ostm1. In summary, our
      data suggest the existence of an alternative CLC-7 operating mode, which is
      active when the protein is not in complex with Ostm1. The vacuolar expression
      system has the potential to become a valuable tool for functional studies on
      intracellular ion channels and transporters from animal cells.

PMID- 22641775
TI  - Rhythmic dendritic Ca2+ oscillations in thalamocortical neurons during slow non
      REM sleep-related activity in vitro.
AB  - The distribution of T-type Ca2+ channels along the entire somatodendritic axis of
      sensory thalamocortical (TC) neurons permits regenerative propagation of low
      threshold spikes (LTS) accompanied by global dendritic Ca2+ influx. Furthermore,
      T-type Ca2+ channels play an integral role in low frequency oscillatory activity
      (<1-4 Hz) that is a defining feature of TC neurons. Nonetheless, the dynamics of
      T-type Ca2+ channel-dependent dendritic Ca2+ signalling during slow sleep
      associated oscillations remains unknown. Here we demonstrate using patch clamp
      recording and two-photon Ca2+ imaging of dendrites from cat TC neurons undergoing
      spontaneous slow oscillatory activity that somatically recorded delta (1-4 Hz)
      and slow (<1 Hz) oscillations are associated with rhythmic and sustained global
      oscillations in dendritic Ca2+. In addition, our data reveal the presence of LTS
      dependent Ca2+ transients (Delta[Ca2+]) in dendritic spine-like structures on
      proximal TC neuron dendrites during slow (<1 Hz) oscillations whose amplitudes
      are similar to those observed in the dendritic shaft. We find that the amplitude
      of oscillation associated Delta[Ca2+] do not vary significantly with distance
      from the soma whereas the decay time constant (taudecay) of Delta[Ca2+] decreases
      significantly in more distal dendrites. Furthermore, taudecay of dendritic
      Delta[Ca2+] increases significantly as oscillation frequency decreases from delta
      to slow frequencies where pronounced depolarised UP states are observed. Such
      rhythmic dendritic Ca2+ entry in TC neurons during sleep-related firing patterns
      could be an important factor in maintaining the oscillatory activity and
      associated biochemical signalling processes, such as synaptic downscaling, that
      occur in non-REM sleep.

PMID- 22641776
TI  - Cells in the monkey ponto-medullary reticular formation modulate their activity
      with slow finger movements.
AB  - Recent work has shown that the primate reticulospinal tract can influence spinal
      interneurons and motoneurons involved in control of the hand. However,
      demonstrating connectivity does not reveal whether reticular outputs are
      modulated during the control of different types of hand movement. Here, we
      investigated how single unit discharge in the pontomedullary reticular formation
      (PMRF) modulated during performance of a slow finger movement task in macaque
      monkeys. Two animals performed an index finger flexion-extension task to track a
      target presented on a computer screen; single units were recorded both from
      ipsilateral PMRF (115 cells) and contralateral primary motor cortex (M1, 210
      cells). Cells in both areas modulated their activity with the task (M1: 87%,
      PMRF: 86%). Some cells (18/115 in PMRF; 96/210 in M1) received sensory input from
      the hand, showing a short-latency modulation in their discharge following a rapid
      passive extension movement of the index finger. Effects in ipsilateral
      electromyogram to trains of stimuli were recorded at 45 sites in the PMRF. These
      responses involved muscles controlling the digits in 13/45 sites (including
      intrinsic hand muscles, 5/45 sites). We conclude that PMRF may contribute to the
      control of fine finger movements, in addition to its established role in control
      of more proximal limb and trunk movements. This finding may be especially
      important in understanding functional recovery after brain lesions such as
      stroke.

PMID- 22641777
TI  - Short-term exercise training improves the cardiovascular response to exercise in
      the postural orthostatic tachycardia syndrome.
AB  - Recent studies have suggested the presence of cardiac atrophy as a key component
      of the pathogenesis of the postural orthostatic tachycardia syndrome (POTS),
      similar to physical deconditioning. It has also been shown that exercise
      intolerance is associated with a reduced stroke volume (SV) in POTS, and that the
      high heart rate (HR) observed at rest and during exercise in these patients is
      due to this low SV. We tested the hypotheses that (a) circulatory control during
      exercise is normal in POTS; and (b) that physical 'reconditioning' with exercise
      training improves exercise performance in patients with POTS. Nineteen (18 women)
      POTS patients completed a 3 month training programme. Cardiovascular responses
      during maximal exercise testing were assessed in the upright position before and
      after training. Resting left ventricular diastolic function was evaluated by
      Doppler echocardiography. Results were compared with those of 10 well-matched
      healthy sedentary controls. A lower SV resulted in a higher HR in POTS at any
      given oxygen uptake (V(O(2))) during exercise while the cardiac output (Q(c))
      V(O(2)) relationship was normal. V(O(2peak)) was lower in POTS than controls
      (26.1 +/- 1.0 (SEM) vs. 36.3 +/- 0.9 ml kg-1 min-1; P < 0.001) due to a lower
      peak SV (65 +/- 3 vs. 80 +/- 5 ml; P = 0.009). After training in POTS, HR became
      lower at any given due to increased SV without changes in the - relationship.
      V(O(2peak)) increased by 11% (P < 0.001) due to increased peak SV (P = 0.021) and
      was proportional to total blood volume. Peak HR was similar, but HR recovery from
      exercise was faster after training than before training (P = 0.036 for training
      and 0.009 for interaction). Resting diastolic function was mostly normal in POTS
      before training, though diastolic suction was impaired (P = 0.023). There were no
      changes in any Doppler index after training. These results suggest that short
      term exercise training improves physical fitness and cardiovascular responses
      during exercise in patients with POTS.

PMID- 22641778
TI  - Interneuron-mediated inhibition synchronizes neuronal activity during slow
      oscillation.
AB  - The signature of slow-wave sleep in the electroencephalogram (EEG) is large
      amplitude fluctuation of the field potential, which reflects synchronous
      alternation of activity and silence across cortical neurons. While initiation of
      the active cortical states during sleep slow oscillation has been intensively
      studied, the biological mechanisms which drive the network transition from an
      active state to silence remain poorly understood. In the current study, using a
      combination of in vivo electrophysiology and thalamocortical network simulation,
      we explored the impact of intrinsic and synaptic inhibition on state transition
      during sleep slow oscillation. We found that in normal physiological conditions,
      synaptic inhibition controls the duration and the synchrony of active state
      termination. The decline of interneuron-mediated inhibition led to asynchronous
      downward transition across the cortical network and broke the regular slow
      oscillation pattern. Furthermore, in both in vivo experiment and computational
      modelling, we revealed that when the level of synaptic inhibition was reduced
      significantly, it led to a recovery of synchronized oscillations in the form of
      seizure-like bursting activity. In this condition, the fast active state
      termination was mediated by intrinsic hyperpolarizing conductances. Our study
      highlights the significance of both intrinsic and synaptic inhibition in
      manipulating sleep slow rhythms.

PMID- 22641779
TI  - Deficiency of sphingomyelin synthase-1 but not sphingomyelin synthase-2 causes
      hearing impairments in mice.
AB  - Sphingomyelin (SM) is a sphingolipid reported to function as a structural
      component of plasma membranes and to participate in signal transduction. The role
      of SM metabolism in the process of hearing remains controversial. Here, we
      examined the role of SM synthase (SMS), which is subcategorized into the family
      members SMS1 and SMS2, in auditory function. Measurements of auditory brainstem
      response (ABR) revealed hearing impairment in SMS1-/- mice in a low frequency
      range (4-16 kHz). As a possible mechanism of this impairment, we found that the
      stria vascularis (SV) in these mice exhibited atrophy and disorganized marginal
      cells. Consequently, SMS1-/- mice exhibited significantly smaller endocochlear
      potentials (EPs). As a possible mechanism for EP reduction, we found altered
      expression patterns and a reduced level of KCNQ1 channel protein in the SV of
      SMS1-/- mice. These mice also exhibited reduced levels of distortion product
      otoacoustic emissions. Quantitative comparison of the SV atrophy, KCNQ1
      expression, and outer hair cell density at the cochlear apical and basal turns
      revealed no location dependence, but more macrophage invasion into the SV was
      observed in the apical region than the basal region, suggesting a role of
      cochlear location-dependent oxidative stress in producing the frequency
      dependence of hearing loss in SMS1-/- mice. Elevated ABR thresholds, decreased
      EPs, and abnormal KCNQ1 expression patterns in SMS1-/- mice were all found to be
      progressive with age. Mice lacking SMS2, however, exhibited neither detectable
      hearing loss nor changes in their EPs. Taken together, our results suggest that
      hearing impairments occur in SMS1-/- but not SMS2-/- mice. Defects in the SV with
      subsequent reductions in EPs together with hair cell dysfunction may account, at
      least partially, for hearing impairments in SMS1-/- mice.

PMID- 22641780
TI  - STIM/Orai signalling complexes in vascular smooth muscle.
AB  - Stromal interaction molecules (STIM1 and STIM2) are single pass transmembrane
      proteins located mainly in the endoplasmic reticulum (ER). STIM proteins contain
      an EF-hand in their N-termini that faces the lumen side of the ER allowing them
      to act as ER calcium (Ca(2+)) sensors. STIM1 has been recognized as central to
      the activation of the highly Ca(2+) selective store-operated Ca(2+) (SOC) entry
      current mediated by the Ca(2+) release-activated Ca(2+) (CRAC) channel; CRAC
      channels are formed by tetramers of the plasma membrane (PM) protein Orai1.
      Physiologically, the production of inositol 1,4,5-trisphosphate (IP(3)) upon
      stimulation of phospholipase C-coupled receptors and the subsequent emptying of
      IP(3)-sensitive ER Ca(2+) stores are sensed by STIM1 molecules which aggregate
      and move closer to the PM to interact physically with Orai1 channels and activate
      Ca(2+) entry. Orai1 has two homologous proteins encoded by separate genes, Orai2
      and Orai3. Other modes of receptor-regulated Ca(2+) entry into cells are store
      independent; for example, arachidonic acid activates a highly Ca(2+) selective
      store-independent channel formed by heteropentamers of Orai1 and Orai3 and
      regulated by the PM pool of STIM1. Here, I will discuss results pertaining to the
      roles of STIM and Orai proteins in smooth muscle Ca(2+) entry pathways and their
      role in vascular remodelling.

PMID- 22641781
TI  - GluN1 splice variant control of GluN1/GluN2D NMDA receptors.
AB  - NMDA receptors are ionotropic glutamate receptors that mediate a slow, Ca2+
      permeable component of excitatory synaptic transmission in the central nervous
      system. Recombinant GluN1-1a/GluN2D receptors are characterized by low channel
      open probability and prolonged deactivation time course following the removal of
      agonist. Here, we show that the deactivation time course, agonist potency, and
      single channel properties of GluN2D-containing NMDA receptors are modulated by
      alternative RNA splicing of GluN1. Our results demonstrate that GluN1 exon 5,
      which encodes a 21-amino-acid insert in the amino-terminal domain, is a key
      determinant of GluN1/GluN2D receptor function. GluN1-1b/GluN2D receptors, which
      contain the residues encoded by exon 5, deactivate with a dual exponential time
      course described by a tauFAST of 410 ms and a tauSLOW of 1100 ms. This time
      course is 3-fold more rapid than that for exon 5-lacking GluN1-1a/GluN2D, which
      deactivates with a tauFAST of 1100 ms and a tauSLOW of 3400 ms. Exon 5-containing
      NMDA receptors also have a two-fold higher open probability (0.037) than exon 5
      lacking receptors (0.017). Furthermore, inclusion of exon 5-encoded residues
      within the GluN1-1b subunit decreases the potency for the endogenous agonist l
      glutamate. Evaluation of receptor kinetics for NMDA receptors containing mutated
      GluN1-1b subunits and wild-type GluN2D identified residue Lys211 in GluN1-1b as a
      key determinant of exon 5 control of the deactivation time course and glutamate
      potency. Evaluation of a kinetic model of GluN1/GluN2D gating suggests that
      residues encoded by exon 5 influence several rate-limiting steps. These data
      demonstrate that the GluN1 subunit is a key determinant of the kinetic and
      pharmacological properties of GluN2D-containing NMDA receptors.

PMID- 22641783
TI  - Disease-causing mutations C277R and C277Y modify gating of human ClC-1 chloride
      channels in myotonia congenita.
AB  - Myotonia congenita is a genetic condition that is caused by mutations in the
      muscle chloride channel gene CLCN1 and characterized by delayed muscle relaxation
      and muscle stiffness. We here investigate the functional consequences of two
      novel disease-causing missense mutations, C277R and C277Y, using heterologous
      expression in HEK293T cells and patch clamp recording. Both mutations reduce
      macroscopic anion currents in transfected cells. Since hClC-1 is a double
      barrelled anion channel, this reduction in current amplitude might be caused by
      altered gating of individual protopores or of joint openings and closing of both
      protopores. We used non-stationary noise analysis and single channel recordings
      to separate the mutants' effects on individual and common gating processes. We
      found that C277Y inverts the voltage dependence and reduces the open
      probabilities of protopore and common gates resulting in decreases of absolute
      open probabilities of homodimeric channels to values below 3%. In heterodimeric
      channels, C277R and C277Y also reduce open probabilities and shift the common
      gate activation curve towards positive potentials. Moreover, C277Y modifies pore
      properties of hClC-1. It reduces single protopore current amplitudes to about two
      thirds of wild-type values, and inverts the anion permeability sequence to I(-) =
      NO(3)(-) >Br(-)>Cl(-). Our findings predict a dramatic reduction of the muscle
      fibre resting chloride conductance and thus fully explain the disease-causing
      effects of mutations C277R and C277Y. Moreover, they provide additional insights
      into the function of C277, a residue recently implicated in common gating of ClC
      channels.

PMID- 22641785
TI  - Cocaine potentiates excitatory drive in the perifornical/lateral hypothalamus.
AB  - The hypothalamus is a critical controller of homeostatic responses and plays a
      fundamental role in reward-seeking behaviour. Recently, hypothalamic neurones in
      the perifornical/lateral hypothalamic area (PF/LHA) have also been implicated in
      drug-seeking behaviour through projections to extra-hypothalamic sites such as
      the ventral tegmental area. For example, a population of neurones that expresses
      the peptide orexin has been strongly implicated in addiction-relevant behaviours.
      To date, the effect of addictive drugs on synaptic properties in the hypothalamus
      remains largely unexplored. Previous studies focusing on the PF/LHA neurones,
      however, have shown that the orexin system exhibits significant plasticity in
      response to food or sleep restriction. This neuroadaptive ability suggests that
      PF/LHA neurones could be highly susceptible to modifications by drug exposure.
      Here, we sought to determine whether cocaine produces synaptic plasticity in
      PF/LHA neurones. Whole-cell patch-clamp techniques were used to examine the
      effects of experimenter-administered (passive) or self-administered (SA) cocaine
      on glutamatergic synaptic transmission in PF/LHA neurones. These experiments
      demonstrate that both passive and SA cocaine exposure increases miniature
      excitatory postsynaptic current (mEPSC) frequency in PF/LHA neurones. In
      addition, SA cocaine reduced the paired-pulse ratio but the AMPA/NMDA ratio of
      evoked excitatory inputs was unchanged, indicative of a presynaptic locus for
      synaptic plasticity. Dual-labelling for orexin and excitatory inputs using the
      vesicular glutamate transporter (VGLUT2), showed that passive cocaine exposure
      increased VGLUT2-positive appositions onto orexin neurones. Further, a population
      of recorded neurones that were filled with neurobiotin and immunolabelled for
      orexin confirmed that increased excitatory drive occurs in this PF/LHA
      population. Given the importance of the PF/LHA and the orexin system in
      modulating drug addiction, we suggest that these cocaine-induced excitatory
      synapse-remodelling events within the hypothalamus may contribute to persistence
      in drug-seeking behaviour and relapse.

PMID- 22641784
TI  - Rapid dopaminergic and GABAergic modulation of calcium and voltage transients in
      dendrites of prefrontal cortex pyramidal neurons.
AB  - The physiological responses of dendrites to dopaminergic inputs are poorly
      understood and controversial. We applied dopamine on one dendritic branch while
      simultaneously monitoring action potentials (APs) from multiple dendrites using
      either calcium-sensitive dye, voltage-sensitive dye or both. Dopaminergic
      suppression of dendritic calcium transients was rapid (<0.5 s) and restricted to
      the site of dopamine application. Voltage waveforms of backpropagating APs were
      minimally altered in the same dendrites where dopamine was confirmed to cause
      large suppression of calcium signals, as determined by dual voltage and calcium
      imaging. The dopamine effects on dendritic calcium transients were fully mimicked
      by D1 agonists, partially reduced by D1 antagonist and completely insensitive to
      protein kinase blockade; consistent with a membrane delimited mechanism. This
      dopamine effect was unaltered in the presence of L-, R- and T-type calcium
      channel blockers. The somatic excitability (i.e. AP firing) was not affected by
      strong dopaminergic stimulation of dendrites. Dopamine and GABA were then
      sequentially applied on the same dendrite. In contrast to dopamine, the pulses of
      GABA prohibited AP backpropagation distally from the application site, even in
      neurons with natural Cl- concentration (patch pipette removed). Thus, the
      neocortex employs at least two distinct mechanisms (dopamine and GABA) for rapid
      modulation of dendritic calcium influx. The spatio-temporal pattern of dendritic
      calcium suppression described in this paper is expected to occur during phasic
      dopaminergic signalling, when midbrain dopaminergic neurons generate a transient
      (0.5 s) burst of APs in response to a salient event.

PMID- 22641787
TI  - Long-term in vivo imaging of normal and pathological mouse spinal cord with
      subcellular resolution using implanted glass windows.
AB  - Repeated in vivo two-photon imaging of adult mammalian spinal cords, with
      subcellular resolution, would be crucial for understanding cellular mechanisms
      under normal and pathological conditions. Current methods are limited because
      they require surgery for each imaging session. Here we report a simple glass
      window methodology avoiding repeated surgical procedures and subsequent
      inflammation. We applied this strategy to follow axon integrity and the
      inflammatory response over months by multicolour imaging of adult transgenic
      mice. We found that glass windows have no significant effect on axon number or
      structure, cause a transient inflammatory response, and dramatically increase the
      throughput of in vivo spinal imaging. Moreover, we used this technique to track
      retraction/degeneration and regeneration of cut axons after a 'pin-prick' spinal
      cord injury with high temporal fidelity. We showed that regenerating axons can
      cross an injury site within 4 days and that their terminals undergo dramatic
      morphological changes for weeks after injury. Overall the technique can
      potentially be adapted to evaluate cellular functions and therapeutic strategies
      in the normal and diseased spinal cord.

PMID- 22641786
TI  - Transcompartmental reversal of single fibre hyperexcitability in juxtaparanodal
      Kv1.1-deficient vagus nerve axons by activation of nodal KCNQ channels.
AB  - Kv1.1 channels cluster at juxtaparanodes of myelinated axons in the vagus nerve,
      the primary conduit for parasympathetic innervation of the heart. Kcna1-null mice
      lacking these channels exhibit neurocardiac dysfunction manifested by atropine
      sensitive atrioventricular conduction blocks and bradycardia that may culminate
      in sudden death. To evaluate whether loss of Kv1.1 channels alters electrogenic
      properties within the nerve, we compared the intrinsic excitability of single
      myelinated A- and Adelta-axons from excised cervical vagus nerves of young adult
      Kcna1-null mice and age-matched, wild-type littermate controls. Although action
      potential shapes and relative refractory periods varied little between genotypes,
      Kv1.1-deficient large myelinated A-axons showed a fivefold increase in
      susceptibility to 4-aminopyridine (4-AP)-induced spontaneous ectopic firing.
      Since the repolarizing currents of juxtaparanodal Kv1 channels and nodal KCNQ
      potassium channels both act to dampen repetitive activity, we examined whether
      augmenting nodal KCNQ activation could compensate for Kv1.1 loss and reverse the
      spontaneous hyperexcitability in Kv1.1-deficient A-axons. Application of the
      selective KCNQ opener flupirtine raised A-axon firing threshold while profoundly
      suppressing 4-AP-induced spontaneous firing, demonstrating a functional synergy
      between the two compartments. We conclude that juxtaparanodal Kv1.1-deficiency
      causes intrinsic hyperexcitability in large myelinated axons in vagus nerve which
      could contribute to autonomic dysfunction in Kcna1-null mice, and that KCNQ
      openers reveal a transcompartmental synergy between Kv1 and KCNQ channels in
      regulating axonal excitability.

PMID- 22641788
TI  - Deliberate use of placebos in clinical practice: what we really know.
AB  - Increasingly a focus of research as well as media reports and online forums, the
      use of placebos in clinical medicine extends beyond sugar pills and saline
      injections. Physician surveys conducted in various countries invariably report
      that placebos are routinely used clinically, impure placebos more frequently than
      the pure ones, and that physicians consider them to be of legitimate therapeutic
      value. Inconsistent study methodologies and physician conceptualisations of
      placebos may complicate the interpretation of survey data, but hardly negate the
      valuable insights these research findings provide. Because impure placebos are
      often not recognised as such by practitioners, they remain at the fringe of many
      placebo-related debates, hence quietly absent from discussions concerning policy
      and regulation. The apparent popularity of impure placebos used in clinical
      practice thus presents unresolved ethical concerns and should direct future
      discussion and research.

PMID- 22641789
TI  - Genome-wide analysis of cis-regulatory divergence between species in the
      Arabidopsis genus.
AB  - Cis-regulatory DNA has been suspected to play a preeminent role in adaptive
      evolution, but understanding the role of cis-regulatory mutations in gene
      expression divergence first requires an accurate analysis of the functional
      differences associated with these regions. We analyzed allele-specific expression
      (ASE) in leaf and floral tissues of F1 interspecific hybrids generated between
      the two closely related species Arabidopsis thaliana and A. lyrata with a whole
      genome SNP (single nucleotide polymorphism) tiling array. We observed 2,205 genes
      showing ASE pattern in at least one tissue. Nearly 90% of genes displaying ASE
      preferentially expressed the allele of A. lyrata. Genome-wide comparison of
      sequence divergence revealed that genes displaying ASE had a higher ratio of
      nonsynonymous to synonymous substitutions in coding regions. We further observe
      that the epigenetic landscape of histone methylation in A. thaliana genome
      associate with ASE. The asymmetry in the direction of allele-specific expression
      suggests interspecific differences in the efficiency of gene silencing in F1
      hybrids.

PMID- 22641790
TI  - The FLU-FOBT Program in community clinics: durable benefits of a randomized
      controlled trial.
AB  - The objective of the study was to determine the extent to which the FLU-FOBT
      Program, a colorectal cancer screening (CRCS) intervention linking the provision
      of fecal occult blood tests (FOBT) to the time of annual influenza vaccination,
      resulted in practice changes in six primary care clinics 1 year after it was
      introduced in a randomized controlled trial (RCT). We assessed CRCS rate changes
      for influenza vaccine recipients, administered brief serial clinic staff surveys
      and interviewed clinic leaders 1 year after the RCT. CRCS rates for influenza
      vaccination recipients between the ages of 50 and 75 years were 42.5% before the
      RCT, 54.5% immediately after the RCT and 55.8% 1 year after the RCT (P < 0.001
      for difference between baseline and 1 year after RCT). Many FLU-FOBT Program
      components were maintained in most clinics at 1-year follow-up. Only 63% of
      clinic staff survey respondents (26 of 41) continued offering FOBT with influenza
      vaccines, but 85% (35 of 41) continued to provide mailing kits with FOBT. Many
      patient education materials were maintained and staff satisfaction with the
      intervention remained high. Clinic leaders acknowledged barriers to maintenance
      but also observed several beneficial practice changes. Many components of the FLU
      FOBT Program were maintained, with beneficial outcomes for participating
      practices.

PMID- 22641792
TI  - Concepts of diabetes self-management in Mexican American and African American low
      income patients with diabetes.
AB  - The goal of the study was to explore low-income minority patients' concepts of
      diabetes self-management and assess the extent to which patient beliefs
      correspond to evidence-based recommendations. African American and Mexican
      American patients with type 2 diabetes were recruited from safety net clinics
      that serve the uninsured and under-insured in Chicago and San Francisco to
      participate in focus group discussions. Grounded theory was used to identify
      themes related to diabetes self-management. Strategies participants mentioned for
      diabetes self-care were medication use, diet, weight loss and exercise. Eating
      more fruit and vegetables and consuming smaller portions were the most commonly
      mentioned dietary behaviors to control diabetes. African Americans expressed
      skepticism about taking medications. Mexican Americans discussed barriers to
      acquiring medications and use of herbal remedies. Mexican Americans frequently
      mentioned intentional exercise of long duration as a management strategy, whereas
      African Americans more frequently described exercise as regular activities of
      daily living. Blood glucose self-monitoring and reducing risks of diabetes
      complications were rarely mentioned as diabetes self-management behaviors.
      African American and Mexican American patients have different concepts of
      diabetes self-management, especially with regard to medication use and physical
      activity. Consideration of these differences may facilitate design of effective
      self-management interventions for these high-risk populations.

PMID- 22641791
TI  - Effectiveness of peer education interventions for HIV prevention, adolescent
      pregnancy prevention and sexual health promotion for young people: a systematic
      review of European studies.
AB  - Peer education remains a popular strategy for health promotion and prevention,
      but evidence of its effectiveness is still limited. This article presents a
      systematic review of peer education interventions in the European Union that were
      published between January 1999 and May 2010. The objective of the review is to
      determine the effectiveness of peer education programs for human immunodeficiency
      virus (HIV) prevention, adolescent pregnancy prevention and promotion of sexual
      health among young people. Standardized methods of searching and data extraction
      were utilized and five studies were identified. Although a few statistically
      significant and non-significant changes were observed in the studies, it is
      concluded that, overall, when compared to standard practice or no intervention,
      there is no clear evidence of the effectiveness of peer education concerning HIV
      prevention, adolescent pregnancy prevention and sexual health promotion for young
      people in the member countries of the European Union. Further research is needed
      to determine factors that contribute to program effectiveness.

PMID- 22641793
TI  - Exploring why young African American women do not change condom-use behavior
      following participation in an STI/HIV prevention intervention.
AB  - Human immunodeficiency virus (HIV) interventions can significantly reduce risky
      sexual behaviors among vulnerable populations. However, not everyone exposed to
      an intervention will reduce their sexual risk behavior. This qualitative study
      sought to identify factors associated with young African American females' lack
      of increase in condom use post-participation in an HIV prevention intervention.
      Semi-structured interviews were conducted with 50 young African American women
      (18-23 years; approximately half were mothers) after participating in a
      demonstrated effective HIV prevention intervention; 24 did not increase condom
      use post-intervention. Interviews were thematically coded for barriers to condom
      use post-intervention. Although nearly all young women reported partner
      associated challenges to using condoms, there were relational differences
      observed among those who changed their condom use versus those who did not. Many
      'non-changers' were engaged in non-stable 'on and off' relationships, with high
      rates of infidelity, often with the father of their child, in which they were
      fearful of requesting condom use. 'Non-changers' also reported more substance
      use, feeling incapable of change and not thinking about condom use. Thus, future
      HIV prevention efforts may benefit from incorporating strategies on how young
      mothers can maintain a non-sexual relationship with their child's father, as well
      as elaborating on the intersection of substance use and risky sexual decision
      making.

PMID- 22641794
TI  - The social ecology of maternal infant care in socially and economically
      marginalized community in southern Israel.
AB  - This study aims to better understand the social ecology of infant care (IC) as
      experienced and perceived by mothers living in a deprived Arab Bedouin community
      in Israel, where children's health indicators are poor. We used the integrative
      model of Garcia Coll et al. (Garcia Coll C, Lamberty G, Jenkins R et al. An
      integrative model for the study of developmental competencies in minority
      children. Child Dev 1996; 67: 1891-914) and constructs of the Health Beliefs
      Model as a study framework for conducting focus groups with 106 mothers in 2007.
      Results show that mothers believe IC and infant well-being are high priorities.
      However, distal barriers, including land disputes, a transition from herding to
      low-paid labor and lifestyle changes have interacted with proximal barriers in
      Bedouin families, including poor living conditions, poverty and weakened familial
      relations to inhibit adequate IC practices. Specifically, distal and proximal
      barriers affect IC directly (e.g. lack of nearby clinics) or indirectly (mothers'
      self-efficacies) to limit mothers' choices and control over IC, thereby posing
      threats to infant health. Our findings demonstrate the importance of
      understanding the complexity of social context in shaping IC among marginalized
      minority mothers and suggest new ground for addressing proximal and distal
      barriers through policy interventions. Without contending with both,
      interventions to strengthen mothers' self-efficacy will have limited success in
      improving the environment of IC and, consequently, infant health.

PMID- 22641795
TI  - "No more psychiatric labels" petition.

PMID- 22641796
TI  - Mental illness does exist.

PMID- 22641797
TI  - Take a stand against "the mayhem of modern psychiatry".

PMID- 22641798
TI  - Likelihood ratios are not good for differential diagnosis.

PMID- 22641800
TI  - Study lacks rigour to determine choice of hip resurfacing or arthroplasty.

PMID- 22641802
TI  - Costs of multidisciplinary teams in cancer are small in relation to benefits.

PMID- 22641803
TI  - Government push for disability over unemployment benefit explains results.

PMID- 22641804
TI  - A tale of two age groups.

PMID- 22641805
TI  - I'm all right, Jack: pull up the ladder.

PMID- 22641806
TI  - Make working into our 70s more palatable.

PMID- 22641807
TI  - Perhaps try a different tack.

PMID- 22641808
TI  - Fight or pensions will be targeted again to fill government deficit.

PMID- 22641809
TI  - Strike for ourselves and social solidarity.

PMID- 22641810
TI  - Pilot study will assess whether HPV test should replace smears to screen for
      cervical cancer.

PMID- 22641811
TI  - NHS promises to ensure modern leadership style to improve staff morale.

PMID- 22641812
TI  - Public health researchers engage with media for greater good, not to boost their
      egos, finds study.

PMID- 22641813
TI  - Raid NHS budget and welfare benefits of well-off older people to boost social
      care funds, Nuffield Trust suggests.

PMID- 22641814
TI  - Role of Na(v)1.9 in activity-dependent axon growth in motoneurons.
AB  - Spontaneous neural activity promotes axon growth in many types of developing
      neurons, including motoneurons. In motoneurons from a mouse model of spinal
      muscular atrophy (SMA), defects in axonal growth and presynaptic function
      correlate with a reduced frequency of spontaneous Ca(2+) transients in axons
      which are mediated by N-type Ca(2+) channels. To characterize the mechanisms that
      initiate spontaneous Ca(2+) transients, we investigated the role of voltage-gated
      sodium channels (VGSCs). We found that low concentrations of the VGSC inhibitors
      tetrodotoxin (TTX) and saxitoxin (STX) reduce the rate of axon growth in cultured
      embryonic mouse motoneurons without affecting their survival. STX was 5- to 10
      fold more potent than TTX and Ca(2+) imaging confirmed that low concentrations of
      STX strongly reduce the frequency of spontaneous Ca(2+) transients in somatic and
      axonal regions. These findings suggest that the Na(V)1.9, a VGSC that opens at
      low thresholds, could act upstream of spontaneous Ca(2+) transients. qPCR from
      cultured and laser-microdissected spinal cord motoneurons revealed abundant
      expression of Na(V)1.9. Na(V)1.9 protein is preferentially localized in axons and
      growth cones. Suppression of Na(V)1.9 expression reduced axon elongation.
      Motoneurons from Na(V)1.9(-/-) mice showed the reduced axon growth in combination
      with reduced spontaneous Ca(2+) transients in the soma and axon terminals. Thus,
      Na(V)1.9 function appears to be essential for activity-dependent axon growth,
      acting upstream of spontaneous Ca(2+) elevation through voltage-gated calcium
      channels (VGCCs). Na(V)1.9 activation could therefore serve as a target for
      modulating axonal regeneration in motoneuron diseases such as SMA in which
      presynaptic activity of VGCCs is reduced.

PMID- 22641815
TI  - Signaling defects in iPSC-derived fragile X premutation neurons.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a leading monogenic
      neurodegenerative disorder affecting premutation carriers of the fragile X (FMR1)
      gene. To investigate the underlying cellular neuropathology, we produced induced
      pluripotent stem cell-derived neurons from isogenic subclones of primary
      fibroblasts of a female premutation carrier, with each subclone bearing
      exclusively either the normal or the expanded (premutation) form of the FMR1 gene
      as the active allele. We show that neurons harboring the stably-active, expanded
      allele (EX-Xa) have reduced postsynaptic density protein 95 protein expression,
      reduced synaptic puncta density and reduced neurite length. Importantly, such
      neurons are also functionally abnormal, with calcium transients of higher
      amplitude and increased frequency than for neurons harboring the normal-active
      allele. Moreover, a sustained calcium elevation was found in the EX-Xa neurons
      after glutamate application. By excluding the individual genetic background
      variation, we have demonstrated neuronal phenotypes directly linked to the FMR1
      premutation. Our approach represents a unique isogenic, X-chromosomal epigenetic
      model to aid the development of targeted therapeutics for FXTAS, and more broadly
      as a model for the study of common neurodevelopmental (e.g. autism) and
      neurodegenerative (e.g. Parkinsonism, dementias) disorders.

PMID- 22641817
TI  - The social network and communicative complexity: preface to theme issue.
AB  - The complex social worlds of many animal species may be linked to complex
      communicative systems in those species. We now have evidence in diverse taxa and
      in different communicative modalities suggesting that complexity in social groups
      can drive complexity in signalling systems. The aim of this theme issue is to
      develop the theory behind this link between social complexity and communicative
      complexity, and to provide an overview of the lines of research testing this
      link.

PMID- 22641816
TI  - The ALS disease protein TDP-43 is actively transported in motor neuron axons and
      regulates axon outgrowth.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease specifically
      affecting cortical and spinal motor neurons. Cytoplasmic inclusions containing
      hyperphosphorylated and ubiquitinated TDP-43 are a pathological hallmark of ALS,
      and mutations in the gene encoding TDP-43 have been directly linked to the
      development of the disease. TDP-43 is a ubiquitous DNA/RNA-binding protein with a
      nuclear role in pre-mRNA splicing. However, the selective vulnerability and
      axonal degeneration of motor neurons in ALS pose the question of whether TDP-43
      may have an additional role in the regulation of the cytoplasmic and axonal fate
      of mRNAs, processes important for neuron function. To investigate this
      possibility, we have characterized TDP-43 localization and dynamics in primary
      cultured motor neurons. Using a combination of cell imaging and biochemical
      techniques, we demonstrate that TDP-43 is localized and actively transported in
      live motor neuron axons, and that it co-localizes with well-studied axonal mRNA
      binding proteins. Expression of the TDP-43 C-terminal fragment led to the
      formation of hyperphosphorylated and ubiquitinated inclusions in motor neuron
      cell bodies and neurites, and these inclusions specifically sequestered the mRNA
      binding protein HuD. Additionally, we showed that overexpression of full-length
      or mutant TDP-43 in motor neurons caused a severe impairment in axon outgrowth,
      which was dependent on the C-terminal protein-interacting domain of TDP-43. Taken
      together, our results suggest a role of TDP-43 in the regulation of axonal
      growth, and suggest that impairment in the post-transcriptional regulation of
      mRNAs in the cytoplasm of motor neurons may be a major factor in the development
      of ALS.

PMID- 22641818
TI  - Social complexity as a proximate and ultimate factor in communicative complexity.
AB  - The 'social complexity hypothesis' for communication posits that groups with
      complex social systems require more complex communicative systems to regulate
      interactions and relations among group members. Complex social systems, compared
      with simple social systems, are those in which individuals frequently interact in
      many different contexts with many different individuals, and often repeatedly
      interact with many of the same individuals in networks over time. Complex
      communicative systems, compared with simple communicative systems, are those that
      contain a large number of structurally and functionally distinct elements or
      possess a high amount of bits of information. Here, we describe some of the
      historical arguments that led to the social complexity hypothesis, and review
      evidence in support of the hypothesis. We discuss social complexity as a driver
      of communication and possible causal factor in human language origins. Finally,
      we discuss some of the key current limitations to the social complexity
      hypothesis-the lack of tests against alternative hypotheses for communicative
      complexity and evidence corroborating the hypothesis from modalities other than
      the vocal signalling channel.

PMID- 22641819
TI  - Multiple time-scales and the developmental dynamics of social systems.
AB  - To build a theory of social complexity, we need to understand how aggregate
      social properties arise from individual interaction rules. Here, I review a body
      of work on the developmental dynamics of pigtailed macaque social organization
      and conflict management that provides insight into the mechanistic causes of
      multi-scale social systems. In this model system coarse-grained, statistical
      representations of collective dynamics are more predictive of the future state of
      the system than the constantly in-flux behavioural patterns at the individual
      level. The data suggest that individuals can perceive and use these
      representations for strategical decision-making. As an interaction history
      accumulates the coarse-grained representations consolidate. This constrains
      individual behaviour and provides the foundations for new levels of organization.
      The time-scales on which these representations change impact whether the
      consolidating higher-levels can be modified by individuals and collectively. The
      time-scales appear to be a function of the 'coarseness' of the representations
      and the character of the collective dynamics over which they are averages. The
      data suggest that an advantage of multiple timescales is that they allow social
      systems to balance tradeoffs between predictability and adaptability. I briefly
      discuss the implications of these findings for cognition, social niche
      construction and the evolution of new levels of organization in biological
      systems.

PMID- 22641820
TI  - Is sociality required for the evolution of communicative complexity? Evidence
      weighed against alternative hypotheses in diverse taxonomic groups.
AB  - Complex social communication is expected to evolve whenever animals engage in
      many and varied social interactions; that is, sociality should promote
      communicative complexity. Yet, informal comparisons among phylogenetically
      independent taxonomic groups seem to cast doubt on the putative role of social
      factors in the evolution of complex communication. Here, we provide a formal test
      of the sociality hypothesis alongside alternative explanations for the evolution
      of communicative complexity. We compiled data documenting variations in signal
      complexity among closely related species for several case study groups--ants,
      frogs, lizards and birds--and used new phylogenetic methods to investigate the
      factors underlying communication evolution. Social factors were only implicated
      in the evolution of complex visual signals in lizards. Ecology, and to some
      degree allometry, were most likely explanations for complexity in the vocal
      signals of frogs (ecology) and birds (ecology and allometry). There was some
      evidence for adaptive evolution in the pheromone complexity of ants, although no
      compelling selection pressure was identified. For most taxa, phylogenetic null
      models were consistently ranked above adaptive models and, for some taxa, signal
      complexity seems to have accumulated in species via incremental or random changes
      over long periods of evolutionary time. Becoming social presumably leads to the
      origin of social communication in animals, but its subsequent influence on the
      trajectory of signal evolution has been neither clear-cut nor general among
      taxonomic groups.

PMID- 22641821
TI  - Social scale and structural complexity in human languages.
AB  - The complexity of different components of the grammars of human languages can be
      quantified. For example, languages vary greatly in the size of their phonological
      inventories, and in the degree to which they make use of inflectional morphology.
      Recent studies have shown that there are relationships between these types of
      grammatical complexity and the number of speakers a language has. Languages
      spoken by large populations have been found to have larger phonological
      inventories, but simpler morphology, than languages spoken by small populations.
      The results require further investigation, and, most importantly, the mechanism
      whereby the social context of learning and use affects the grammatical evolution
      of a language needs elucidation.

PMID- 22641822
TI  - Bridging the bonding gap: the transition from primates to humans.
AB  - Primate societies are characterized by bonded social relationships of a kind that
      are rare in other mammal taxa. These bonded relationships, which provide the
      basis for coalitions, are underpinned by an endorphin mechanism mediated by
      social grooming. However, bonded relationships of this kind impose constraints on
      the size of social groups that are possible. When ecological pressures have
      demanded larger groups, primates have had to evolve new mechanisms to facilitate
      bonding. This has involved increasing the size of vocal and visual communication
      repertoires, increasing the time devoted to social interaction and developing a
      capacity to manage two-tier social relationships (strong and weak ties). I
      consider the implications of these constraints for the evolution of human social
      communities and argue that laughter was an early evolutionary innovation that
      helped bridge the bonding gap between the group sizes characteristic of
      chimpanzees and australopithecines and those in later hominins.

PMID- 22641824
TI  - Social drive and the evolution of primate hearing.
AB  - The structure and function of primate communication have attracted much
      attention, and vocal signals, in particular, have been studied in detail. As a
      general rule, larger social groups emit more types of vocal signals, including
      those conveying the presence of specific types of predators. The adaptive
      advantages of receiving and responding to alarm calls are expected to exert a
      selective pressure on the auditory system. Yet, the comparative biology of
      primate hearing is limited to select species, and little attention has been paid
      to the effects of social and vocal complexity on hearing. Here, we use the
      auditory brainstem response method to generate the largest number of standardized
      audiograms available for any primate radiation. We compared the auditory
      sensitivities of 11 strepsirrhine species with and without independent contrasts
      and show that social complexity explains a significant amount of variation in two
      audiometric parameters-overall sensitivity and high-frequency limit. We verified
      the generality of this latter result by augmenting our analysis with published
      data from nine species spanning the primate order. To account for these findings,
      we develop and test a model of social drive. We hypothesize that social
      complexity has favoured enhanced hearing sensitivities, especially at higher
      frequencies.

PMID- 22641823
TI  - Derived vocalizations of geladas (Theropithecus gelada) and the evolution of
      vocal complexity in primates.
AB  - Primates are intensely social and exhibit extreme variation in social structure,
      making them particularly well suited for uncovering evolutionary connections
      between sociality and vocal complexity. Although comparative studies find a
      correlation between social and vocal complexity, the function of large vocal
      repertoires in more complex societies remains unclear. We compared the vocal
      complexity found in primates to both mammals in general and human language in
      particular and found that non-human primates are not unusual in the complexity of
      their vocal repertoires. To better understand the function of vocal complexity
      within primates, we compared two closely related primates (chacma baboons and
      geladas) that differ in their ecology and social structures. A key difference is
      that gelada males form long-term bonds with the 2-12 females in their harem-like
      reproductive unit, while chacma males primarily form temporary consortships with
      females. We identified homologous and non-homologous calls and related the use of
      the derived non-homologous calls to specific social situations. We found that the
      socially complex (but ecologically simple) geladas have larger vocal repertoires.
      Derived vocalizations of geladas were primarily used by leader males in
      affiliative interactions with 'their' females. The derived calls were frequently
      used following fights within the unit suggesting that maintaining cross-sex bonds
      within a reproductive unit contributed to this instance of evolved vocal
      complexity. Thus, our comparison highlights the utility of using closely related
      species to better understand the function of vocal complexity.

PMID- 22641825
TI  - Evolving communicative complexity: insights from rodents and beyond.
AB  - Social living goes hand in hand with communication, but the details of this
      relationship are rarely simple. Complex communication may be described by
      attributes as diverse as a species' entire repertoire, signallers'
      individualistic signatures, or complex acoustic phenomena within single calls.
      Similarly, attributes of social complexity are diverse and may include group
      size, social role diversity, or networks of interactions and relationships. How
      these different attributes of social and communicative complexity co-evolve is an
      active question in behavioural ecology. Sciurid rodents (ground squirrels,
      prairie dogs and marmots) provide an excellent model system for studying these
      questions. Sciurid studies have found that demographic role complexity predicts
      alarm call repertoire size, while social group size predicts alarm call
      individuality. Along with other taxa, sciurids reveal an important insight:
      different attributes of sociality are linked to different attributes of
      communication. By breaking social and communicative complexity down to different
      attributes, focused studies can better untangle the underlying evolutionary
      relationships and move us closer to a comprehensive theory of how sociality and
      communication evolve.

PMID- 22641826
TI  - Linking social complexity and vocal complexity: a parid perspective.
AB  - The Paridae family (chickadees, tits and titmice) is an interesting avian group
      in that species vary in important aspects of their social structure and many
      species have large and complex vocal repertoires. For this reason, parids
      represent an important set of species for testing the social complexity
      hypothesis for vocal communication--the notion that as groups increase in social
      complexity, there is a need for increased vocal complexity. Here, we describe the
      hypothesis and some of the early evidence that supported the hypothesis. Next, we
      review literature on social complexity and on vocal complexity in parids, and
      describe some of the studies that have made explicit tests of the social
      complexity hypothesis in one parid--Carolina chickadees, Poecile carolinensis. We
      conclude with a discussion, primarily from a parid perspective, of the benefits
      and costs of grouping and of physiological factors that might mediate the
      relationship between social complexity and changes in signalling behaviour.

PMID- 22641827
TI  - Social networks and the development of social skills in cowbirds.
AB  - The complex interrelationships among individuals within social environments can
      exert selection pressures on social skills: those behaviours and cognitive
      processes that allow animals to manipulate and out-reproduce others. Social
      complexity can also have a developmental effect on social skills by providing
      individuals with opportunities to hone their skills by dealing with the
      challenges posed in within-group interactions. We examined how social skills
      develop in captive, adult male brown-headed cowbirds (Molothrus ater) that were
      exposed to differing levels of 'social complexity' across a 2-year experiment.
      After each year, subjects housed in groups with dynamic social structure (where
      many individuals entered and exited the groups during the year) outcompeted birds
      who had been housed in static groups. Exposure to dynamic structure subsequently
      led to substantial changes to the social networks of the home conditions during
      the breeding season. Static groups were characterized by a predictable
      relationship between singing and reproductive success that was stable across
      years. In dynamic conditions, however, males showed significant variability in
      their dominance status, their courting and even in their mating success.
      Reproductive success of males varied dramatically across years and was responsive
      to social learning in adulthood, and socially dynamic environments 'trained'
      individuals to be better competitors, even at an age when the development of many
      traits important for breeding (like song quality) had ended.

PMID- 22641828
TI  - Face to face with the social brain.
AB  - Recent comparative evidence suggests that anthropoid primates are the only
      vertebrates to exhibit a quantitative relationship between relative brain size
      and social group size. In this paper, I attempt to explain this pattern with
      regard to facial expressivity and social bonding. I hypothesize that facial motor
      control increases as a secondary consequence of neocortical expansion owing to
      cortical innervation of the facial motor nucleus. This is supported by new
      analyses demonstrating correlated evolution between relative neocortex size and
      relative facial nucleus size. I also hypothesize that increased facial motor
      control correlates with enhanced emotional expressivity, which provides the
      opportunity for individuals to better gauge the trustworthiness of group members.
      This is supported by previous evidence from human psychology, as well as new
      analyses demonstrating a positive relationship between allogrooming and facial
      nucleus volume. I suggest new approaches to the study of primate facial
      expressivity in light of these hypotheses.

PMID- 22641829
TI  - Eulemur, me lemur: the evolution of scent-signal complexity in a primate clade.
AB  - Signal complexity has been linked to social complexity in vocal, but not
      chemical, communication. To address this gap, we examined the chemical complexity
      of male and female glandular secretions in eight species of Eulemur. In this
      diverse clade of macrosmatic primates, species differ by social or mating system
      and dominance structure. We applied principal component and linear discriminate
      analyses to data obtained by gas chromatography/mass spectrometry. Beyond the
      significant effects on chemical signals of gland type, sex, season and species,
      we found effects of social variables and phylogeny. Notably, female odours were
      more chemically complex in multimale-multifemale species than pair-bonded
      species, whereas male odours were more chemically complex in codominant species
      than female-dominant species. Also, the traditional sexual dimorphism, whereby
      male signal complexity exceeds that of females, was present in codominant
      species, but reversed in female-dominant species. Lastly, a positive relationship
      between the species' pairwise chemical distances and their pairwise phylogenetic
      distances supported a gradual, but relatively fast mode of signal evolution. We
      suggest that the comparative method can be a powerful tool in olfactory research,
      revealing species differences relevant to the understanding of current signal
      utility and evolutionary processes. In particular, social complexity in lemurs
      may have selected for olfactory complexity.

PMID- 22641830
TI  - Drug companies and publishers set out 10 steps to enhance credibility of industry
      sponsored trials.

PMID- 22641831
TI  - World leaders agree to cut deaths from non-communicable diseases by a quarter by
      2025.

PMID- 22641832
TI  - Surgeon whose "mistake" left four year old boy with colostomy bag gets three
      month suspension.

PMID- 22641833
TI  - Plan to stimulate research in developing countries is put on hold.

PMID- 22641834
TI  - Urologist is jailed after admitting manslaughter of woman with kidney infection.

PMID- 22641835
TI  - Latitudinal variation in protein expression after heat stress in the salt marsh
      mussel Geukensia demissa.
AB  - Individuals of a broadly distributed species often experience significantly
      different environmental conditions depending on location. For example, the mussel
      Geukensia demissa occurs intertidally from the Gulf of St. Lawrence to central
      Florida; within this range, northern populations are exposed to temperatures cold
      enough to freeze the tissue, whereas southern populations can experience
      temperatures approaching the species' upper lethal limit. Thus, G. demissa
      provides an ideal system with which to study physiological variation in
      conspecifics occurring across a broad latitudinal range. We collected G. demissa
      at five sites from Maine to Florida, encompassing a range of 1900 km, and have
      used a proteomic approach to describe how protein expression varies in
      individuals from the different locations. We acclimated individuals from each
      site to common conditions (18 degrees C) for 4 weeks, and exposed a subset of
      these to acute heat stress (40 degrees C). We separated gill proteins using two
      dimensional gel electrophoresis and quantified abundances of the resulting
      protein spots. Among mussels acclimated to 18 degrees C protein, expression
      profiles were more similar among individuals from the same site than among sites,
      but there was no discernible correlation with latitude. In contrast, after acute
      heat stress, protein expression among mussels from different locations varied
      substantially, with 31 of 448 proteins changing in abundance in the northernmost
      (Maine) group, compared with 5-11 proteins in the four southern groups.
      Identification of 27 of these proteins revealed five functional clusters:
      chaperones, cytoskeletal proteins, oxidative stress proteins, regulatory
      proteins, and a translation initiation factor. Across these functional
      categories, the two northernmost groups, Maine and New York, showed the greatest
      number of proteins that changed significantly in abundance, as well as the
      greatest fold-change in abundance for many of the proteins. We conclude that the
      northern populations of G. demissa are physiologically distinct from the southern
      groups, and that the differences in protein-expression profiles are consistent
      with greater sensitivity to heat stress to the north.

PMID- 22641836
TI  - Proteomics to assess the role of phenotypic plasticity in aquatic organisms
      exposed to pollution and global warming.
AB  - Nowadays, the unprecedented rates of anthropogenic changes in ecosystems suggest
      that organisms have to migrate to new distributional ranges or to adapt
      commensurately quickly to new conditions to avoid becoming extinct. Pollution and
      global warming are two of the most important threats aquatic organisms will have
      to face in the near future. If genetic changes in a population in response to
      natural selection are extensively studied, the role of acclimation through
      phenotypic plasticity (the property of a given genotype to produce different
      phenotypes in response to particular environmental conditions) in a species to
      deal with new environmental conditions remains largely unknown. Proteomics is the
      extensive study of the protein complement of a genome. It is dynamic and depends
      on the specific tissue, developmental stage, and environmental conditions. As the
      final product of gene expression, it is subjected to several regulatory steps
      from gene transcription to the functional protein. Consequently, there is a
      discrepancy between the abundance of mRNA and the abundance of the corresponding
      protein. Moreover, proteomics is closer to physiology and gives a more functional
      knowledge of the regulation of gene expression than does transcriptomics. The
      study of protein-expression profiles, however, gives a better portrayal of the
      cellular phenotype and is considered as a key link between the genotype and the
      organismal phenotype. Under new environmental conditions, we can observe a shift
      of the protein-expression pattern defining a new cellular phenotype that can
      possibly improve the fitness of the organism. It is now necessary to define a
      proteomic norm of reaction for organisms acclimating to environmental stressors.
      Its link to fitness will give new insights into how organisms can evolve in a
      changing environment. The proteomic literature bearing on chronic exposure to
      pollutants and on acclimation to heat stress in aquatic organisms, as well as
      potential application of proteomics in evolutionary issues, are outlined. While
      the transcriptome responses are commonly investigated, proteomics approaches now
      need to be intensified, with the new perspective of integrating the cellular
      phenotype with the organismal phenotype and with the mechanisms of the regulation
      of gene expression, such as epigenetics.

PMID- 22641837
TI  - A power calculation guide for fMRI studies.
AB  - In the past, power analyses were not that common for fMRI studies, but recent
      advances in power calculation techniques and software development are making
      power analyses much more accessible. As a result, power analyses are more
      commonly expected in grant applications proposing fMRI studies. Even though the
      software is somewhat automated, there are important decisions to be made when
      setting up and carrying out a power analysis. This guide provides tips on
      carrying out power analyses, including obtaining pilot data, defining a region of
      interest and other choices to help create reliable power calculations.

PMID- 22641839
TI  - Contact refusal by children following acrimonious separation: therapeutic
      approaches with children and parents.
AB  - This paper aims to build on the existing literature, by presenting some thoughts
      based on clinical experience with nine families of children referred for
      intractable contact refusal with one parent following marital separation. This
      particular group of high-conflict divorce cases engenders an inordinate amount of
      frustration both within the courts and therapeutic agencies. We outline here our
      assessment process and therapeutic strategies, as well as consideration of the
      role of the wider professional system and the courts. We conclude that whether or
      not direct contact with the rejected parent is achieved, useful therapeutic work
      can be carried out to assist children in moving on with their lives.

PMID- 22641838
TI  - A Bayesian account of 'hysteria'.
AB  - This article provides a neurobiological account of symptoms that have been called
      'hysterical', 'psychogenic' or 'medically unexplained', which we will call
      functional motor and sensory symptoms. We use a neurobiologically informed model
      of hierarchical Bayesian inference in the brain to explain functional motor and
      sensory symptoms in terms of perception and action arising from inference based
      on prior beliefs and sensory information. This explanation exploits the key
      balance between prior beliefs and sensory evidence that is mediated by (body
      focused) attention, symptom expectations, physical and emotional experiences and
      beliefs about illness. Crucially, this furnishes an explanation at three
      different levels: (i) underlying neuromodulatory (synaptic) mechanisms; (ii)
      cognitive and experiential processes (attention and attribution of agency); and
      (iii) formal computations that underlie perceptual inference (representation of
      uncertainty or precision). Our explanation involves primary and secondary
      failures of inference; the primary failure is the (autonomous) emergence of a
      percept or belief that is held with undue certainty (precision) following top
      down attentional modulation of synaptic gain. This belief can constitute a
      sensory percept (or its absence) or induce movement (or its absence). The
      secondary failure of inference is when the ensuing percept (and any somatosensory
      consequences) is falsely inferred to be a symptom to explain why its content was
      not predicted by the source of attentional modulation. This account accommodates
      several fundamental observations about functional motor and sensory symptoms,
      including: (i) their induction and maintenance by attention; (ii) their
      modification by expectation, prior experience and cultural beliefs and (iii)
      their involuntary and symptomatic nature.

PMID- 22641840
TI  - Repair of paravalvular prosthetic mitral valve leaks with septal occluder devices
      in severely high-risk patients: a word of caution.
AB  - Paravalvular leak following a mitral valve replacement is a complication seen in
      approximately 1 of 10 replacements. The corrective method has traditionally been
      reoperation. Septal occluder devices are more commonly being utilized as an
      alternative percutaneous correction method. We report the use of septal occluder
      devices in the repair of mitral paravalvular leak in two patients at severely
      high EuroSCORE II mortality risk. In both patients, the occluder devices became
      unstable, leading to a recurrence of severe paravalvular leak.

PMID- 22641841
TI  - Neutrophil elastase activity in pulmonary venous blood during lung resection.
AB  - OBJECTIVES: Neutrophil elastase has been reported to play an important role in
      acute lung injury, which is a major cause of postoperative mortality after
      pulmonary resection. Neutrophil elastase released in the lungs reaches the
      peripheral circulation via the pulmonary veins. This study was performed to
      compare neutrophil elastase activity in pulmonary venous blood (collected during
      lobectomy) with that in the peripheral blood, and to determine the perioperative
      changes of neutrophil elastase activity. METHODS: In 34 patients undergoing
      lobectomy with mediastinal lymph node dissection, the leucocyte count, neutrophil
      count, neutrophil elastase activity and levels of tumour necrosis factor-alpha,
      interleukin-6 and interleukin-8 were measured in the pulmonary venous blood and
      peripheral arterial blood before and after surgery. Then, these parameters were
      compared between before and after surgery with peripheral and pulmonary blood.
      RESULTS: Neutrophil elastase activity was found to be significantly higher in
      pulmonary venous blood at the completion of surgery than at the start (during
      thoracotomy), while the neutrophil elastase activity of peripheral arterial blood
      showed no significant change between the start and completion of surgery.
      CONCLUSIONS: In conclusion, measurement of neutrophil elastase activity in
      pulmonary venous blood revealed changes associated with lobectomy.

PMID- 22641842
TI  - Simultaneous complex single ventricle palliation and tracheoplasty for heterotaxy
      syndrome.
AB  - Although isomerism of the bronchial tree is an integral part of hetrotaxy
      syndrome, the association of congenital tracheal stenosis is rare in this group
      of disorders, and it has not yet been thoroughly described in the literature.
      This condition is potentially life-threatening and precludes single ventricle
      palliation. This report presents the case of a 5-month old infant with
      symptomatic congenital tracheal stenosis, functionally univentricular heart and
      extracardiac total anomalous pulmonary venous connection (TAPVC). The condition
      was successfully treated with bidirectional Glenn anastomosis, central pulmonary
      artery plasty, repair of TAPVC and slide tracheoplasty.

PMID- 22641843
TI  - Doctors' voices in patients' narratives: coping with emotions in storytelling.
AB  - OBJECTIVES: To understand doctors' impacts on the emotional coping of patients,
      their stories about encounters with doctors are used. These accounts reflect
      meaning-making processes and biographically contextualized experiences. We
      investigate how patients characterize their doctors by voicing them in their
      stories, thus assigning them functions in their coping process. METHODS: 394
      narrated scenes with reported speech of doctors were extracted from interviews
      with 26 patients with type 2 diabetes and 30 with chronic pain. Constructed
      speech acts were investigated by means of positioning and narrative analysis, and
      assigned into thematic categories by a bottom-up coding procedure. RESULTS:
      Patients use narratives as coping strategies when confronted with illness and
      their encounters with doctors by constructing them in a supportive and face
      saving way. In correspondence with the variance of illness conditions, differing
      moral problems in dealing with doctors arise. Different evaluative stances
      towards the same events within interviews show that positionings are not fixed,
      but vary according to contexts and purposes. DISCUSSION: Our narrative approach
      deepens the standardized and predominantly cognitive statements of questionnaires
      in research on doctor-patient relations by individualized emotional and
      biographical aspects of patients' perspective. Doctors should be trained to
      become aware of their impact in patients' coping processes.

PMID- 22641844
TI  - Ultrasound stimulation restores impaired neovascularization-related capacities of
      human circulating angiogenic cells.
AB  - AIMS: Unsatisfactory effects of therapeutic angiogenesis in critical limb
      ischaemia may be ascribed to use of circulating angiogenic cells (CACs) derived
      from atherosclerotic patients with impaired neovascularization-related
      capacities. We tested whether ultrasound cell stimulation can restore the
      impaired capacities. METHODS AND RESULTS: During culture of human peripheral
      blood-derived mononuclear cells for 4 days to achieve CACs, we stimulated the
      cells in culture daily with low-intensity pulsed ultrasound stimulation (LIPUS).
      Application of LIPUS to cells in culture derived from healthy volunteers
      augmented the generation and migration capacities of CACs, increased
      concentrations of angiopoietin 2 and nitrogen oxides in the culture medium, and
      increased the expression of phosphorylated-Akt and endothelial nitric oxide
      synthase in CACs on western blotting. Application of LIPUS to cells in culture
      derived from atherosclerotic patients also augmented the generation and migration
      capacities of CACs. Although neovascularization in the ischaemic hindlimb of
      athymic nude mice was impaired after intramuscular injection of CACs derived from
      atherosclerotic patients compared with that using CACs derived from healthy
      volunteers, LIPUS of the cells in culture derived from atherosclerotic patients
      restored the neovascularization capacities. CONCLUSION: Therapeutic angiogenesis
      with LIPUS-pre-treated CACs may be a new strategy to rescue critical limb
      ischaemia in atherosclerotic patients.

PMID- 22641845
TI  - Roles of Dppa2 in the regulation of the present status and future of pluripotent
      stem cells.
AB  - Maintenance of undifferentiated states of pluripotent embryonic stem cells is
      regulated by a complex network of transcription factors and signaling pathways.
      Recent reports revealed that developmental pluripotency-associated 2 (Dppa2),
      which regulates chromatin structures, plays important roles in the maintenance of
      pluripotency and proliferation of embryonic stem cells. Interestingly,
      developmental pluripotency-associated 2 is involved not only in the normal
      development of lung but also in the pathogenesis of non-small cell lung cancers.
      These results suggest that an epigenetic regulator of pluripotent stem cells
      plays important roles in normal development and tumorigenesis.

PMID- 22641846
TI  - Mycobacterium smegmatis SftH exemplifies a distinctive clade of superfamily II
      DNA-dependent ATPases with 3' to 5' translocase and helicase activities.
AB  - Bacterial DNA helicases are nucleic acid-dependent NTPases that play important
      roles in DNA replication, recombination and repair. We are interested in the DNA
      helicases of Mycobacteria, a genus of the phylum Actinobacteria, which includes
      the human pathogen Mycobacterium tuberculosis and its avirulent relative
      Mycobacterium smegmatis. Here, we identify and characterize M. smegmatis SftH, a
      superfamily II helicase with a distinctive domain structure, comprising an N
      terminal NTPase domain and a C-terminal DUF1998 domain (containing a putative
      tetracysteine metal-binding motif). We show that SftH is a monomeric DNA
      dependent ATPase/dATPase that translocates 3' to 5' on single-stranded DNA and
      has 3' to 5' helicase activity. SftH homologs are found in bacteria representing
      12 different phyla, being especially prevalent in Actinobacteria (including M.
      tuberculosis). SftH homologs are evident in more than 30 genera of Archaea. Among
      eukarya, SftH homologs are present in plants and fungi.

PMID- 22641847
TI  - Targeting duplex DNA with chimeric alpha,beta-triplex-forming oligonucleotides.
AB  - Triplex-directed DNA recognition is strictly limited by polypurine sequences. In
      an attempt to address this problem with synthetic biology tools, we designed a
      panel of short chimeric alpha,beta-triplex-forming oligonucleotides (TFOs) and
      studied their interaction with fluorescently labelled duplex hairpins using
      various techniques. The hybridization of hairpin with an array of chimeric probes
      suggests that recognition of double-stranded DNA follows complicated rules
      combining reversed Hoogsteen and non-canonical homologous hydrogen bonding. In
      the presence of magnesium ions, chimeric TFOs are able to form highly stable
      alpha,beta-triplexes, as indicated by native gel-electrophoresis, on-array
      thermal denaturation and fluorescence-quenching experiments. CD spectra of
      chimeric triplexes exhibited features typically observed for anti-parallel purine
      triplexes with a GA or GT third strand. The high potential of chimeric alpha,beta
      TFOs in targeting double-stranded DNA was demonstrated in the EcoRI endonuclease
      protection assay. In this paper, we report, for the first time, the recognition
      of base pair inversions in a duplex by chimeric TFOs containing alpha-thymidine
      and alpha-deoxyguanosine.

PMID- 22641848
TI  - Hydrogen bond formation between the naturally modified nucleobase and phosphate
      backbone.
AB  - Natural RNAs, especially tRNAs, are extensively modified to tailor structure and
      function diversities. Uracil is the most modified nucleobase among all natural
      nucleobases. Interestingly, >76% of uracil modifications are located on its 5
      position. We have investigated the natural 5-methoxy (5-O-CH(3)) modification of
      uracil in the context of A-form oligonucleotide duplex. Our X-ray crystal
      structure indicates first a H-bond formation between the uracil 5-O-CH(3) and its
      5'-phosphate. This novel H-bond is not observed when the oxygen of 5-O-CH(3) is
      replaced with a larger atom (selenium or sulfur). The 5-O-CH(3) modification does
      not cause significant structure and stability alterations. Moreover, our
      computational study is consistent with the experimental observation. The
      investigation on the uracil 5-position demonstrates the importance of this RNA
      modification at the atomic level. Our finding suggests a general interaction
      between the nucleobase and backbone and reveals a plausible function of the tRNA
      5-O-CH(3) modification, which might potentially rigidify the local conformation
      and facilitates translation.

PMID- 22641849
TI  - Folding path of P5abc RNA involves direct coupling of secondary and tertiary
      structures.
AB  - Folding mechanisms in which secondary structures are stabilized through the
      formation of tertiary interactions are well documented in protein folding but
      challenge the folding hierarchy normally assumed for RNA. However, it is
      increasingly clear that RNA could fold by a similar mechanism. P5abc, a small
      independently folding tertiary domain of the Tetrahymena thermophila group I
      ribozyme, is known to fold by a secondary structure rearrangement involving helix
      P5c. However, the extent of this rearrangement and the precise stage of folding
      that triggers it are unknown. We use experiments and simulations to show that the
      P5c helix switches to the native secondary structure late in the folding pathway
      and is directly coupled to the formation of tertiary interactions in the A-rich
      bulge. P5c mutations show that the switch in P5c is not rate-determining and
      suggest that non-native interactions in P5c aid folding rather than impede it.
      Our study illustrates that despite significant differences in the building blocks
      of proteins and RNA, there may be common ways in which they self-assemble.

PMID- 22641850
TI  - GGRNA: an ultrafast, transcript-oriented search engine for genes and transcripts.
AB  - GGRNA (http://GGRNA.dbcls.jp/) is a Google-like, ultrafast search engine for
      genes and transcripts. The web server accepts arbitrary words and phrases, such
      as gene names, IDs, gene descriptions, annotations of gene and even
      nucleotide/amino acid sequences through one simple search box, and quickly
      returns relevant RefSeq transcripts. A typical search takes just a few seconds,
      which dramatically enhances the usability of routine searching. In particular,
      GGRNA can search sequences as short as 10 nt or 4 amino acids, which cannot be
      handled easily by popular sequence analysis tools. Nucleotide sequences can be
      searched allowing up to three mismatches, or the query sequences may contain
      degenerate nucleotide codes (e.g. N, R, Y, S). Furthermore, Gene Ontology
      annotations, Enzyme Commission numbers and probe sequences of catalog microarrays
      are also incorporated into GGRNA, which may help users to conduct searches by
      various types of keywords. GGRNA web server will provide a simple and powerful
      interface for finding genes and transcripts for a wide range of users. All
      services at GGRNA are provided free of charge to all users.

PMID- 22641851
TI  - Characterization and prediction of the binding site in DNA-binding proteins:
      improvement of accuracy by combining residue composition, evolutionary
      conservation and structural parameters.
AB  - We present a set of four parameters that in combination can predict DNA-binding
      residues on protein structures to a high degree of accuracy. These are the number
      of evolutionary conserved residues (N(cons)) and their spatial clustering
      (rho(e)), hydrogen bond donor capability (D(p)) and residue propensity (R(p)). We
      first used these parameters to characterize 130 interfaces in a set of 126 DNA
      binding proteins (DBPs). The applicability of these parameters both individually
      and in combination, to distinguish the true binding region from the rest of the
      protein surface was then analyzed. R(p) shows the best performance identifying
      the true interface with the top rank in 83% cases. Importantly, we also used the
      unbound-bound test cases of the protein-DNA docking benchmark to test the
      efficacy of our method. When applied to the unbound form of the DBPs, R(p) can
      distinguish 86% cases. Finally, we have applied the SVM approach for recognizing
      the interface region using the above parameters along with the individual amino
      acid composition as attributes. The accuracy of prediction is 90.5% for the bound
      structures and 93.6% for the unbound form of the proteins.

PMID- 22641852
TI  - RNase MRP RNA and RNase P activity in plants are associated with a Pop1p
      containing complex.
AB  - RNase P processes the 5'-end of tRNAs. An essential catalytic RNA has been
      demonstrated in Bacteria, Archaea and the nuclei of most eukaryotes; an organism
      specific number of proteins complement the holoenzyme. Nuclear RNase P from yeast
      and humans is well understood and contains an RNA, similar to the sister enzyme
      RNase MRP. In contrast, no protein subunits have yet been identified in the plant
      enzymes, and the presence of a nucleic acid in RNase P is still enigmatic. We
      have thus set out to identify and characterize the subunits of these enzymes in
      two plant model systems. Expression of the two known Arabidopsis MRP RNA genes in
      vivo was verified. The first wheat MRP RNA sequences are presented, leading to
      improved structure models for plant MRP RNAs. A novel mRNA encoding the central
      RNase P/MRP protein Pop1p was identified in Arabidopsis, suggesting the
      expression of distinct protein variants from this gene in vivo. Pop1p-specific
      antibodies precipitate RNase P activity and MRP RNAs from wheat extracts. Our
      results provide evidence that in plants, Pop1p is associated with MRP RNAs and
      with the catalytic subunit of RNase P, either separately or in a single large
      complex.

PMID- 22641853
TI  - CombFunc: predicting protein function using heterogeneous data sources.
AB  - Only a small fraction of known proteins have been functionally characterized,
      making protein function prediction essential to propose annotations for
      uncharacterized proteins. In recent years many function prediction methods have
      been developed using various sources of biological data from protein sequence and
      structure to gene expression data. Here we present the CombFunc web server, which
      makes Gene Ontology (GO)-based protein function predictions. CombFunc
      incorporates ConFunc, our existing function prediction method, with other
      approaches for function prediction that use protein sequence, gene expression and
      protein-protein interaction data. In benchmarking on a set of 1686 proteins
      CombFunc obtains precision and recall of 0.71 and 0.64 respectively for gene
      ontology molecular function terms. For biological process GO terms precision of
      0.74 and recall of 0.41 is obtained. CombFunc is available at
      http://www.sbg.bio.ic.ac.uk/combfunc.

PMID- 22641854
TI  - DroPNet: a web portal for integrated analysis of Drosophila protein-protein
      interaction networks.
AB  - DroPNet (Drosophila Protein Network) is a Drosophila-dedicated web portal for
      generating and analyzing protein-protein interaction (PPI) networks. This
      platform integrates users' experimental data provided as one or two lists of
      genes with PPI data from Drosophila and other species. These experimental data
      can, for example, come from RNAi screens, for which this approach is known to be
      valuable. DroPNet, therefore, provides an essential basis for further biological
      analysis by linking functional and physical interactions and reinforcing the
      relevance of each. DroPNet focuses on the search of PPIs between genes of the
      entry list, and includes the possibility of searching for intermediate genes for
      which the corresponding protein indirectly links two entry data. It also offers
      multiple functions for editing the networks obtained, providing users with
      interactive possibilities to progressively improve and refine the results. This
      approach gives a global view of the studied process and makes it possible to
      highlight specific interactions that have so far been understudied. DroPNet is
      freely available at http://dropnet.isima.fr.

PMID- 22641855
TI  - KD4v: Comprehensible Knowledge Discovery System for Missense Variant.
AB  - A major challenge in the post-genomic era is a better understanding of how human
      genetic alterations involved in disease affect the gene products. The KD4v
      (Comprehensible Knowledge Discovery System for Missense Variant) server allows to
      characterize and predict the phenotypic effects (deleterious/neutral) of missense
      variants. The server provides a set of rules learned by Induction Logic
      Programming (ILP) on a set of missense variants described by conservation,
      physico-chemical, functional and 3D structure predicates. These rules are
      interpretable by non-expert humans and are used to accurately predict the
      deleterious/neutral status of an unknown mutation. The web server is available at
      http://decrypthon.igbmc.fr/kd4v.

PMID- 22641856
TI  - Quantifying selection in high-throughput Immunoglobulin sequencing data sets.
AB  - High-throughput immunoglobulin sequencing promises new insights into the somatic
      hypermutation and antigen-driven selection processes that underlie B-cell
      affinity maturation and adaptive immunity. The ability to estimate positive and
      negative selection from these sequence data has broad applications not only for
      understanding the immune response to pathogens, but is also critical to
      determining the role of somatic hypermutation in autoimmunity and B-cell cancers.
      Here, we develop a statistical framework for Bayesian estimation of Antigen
      driven SELectIoN (BASELINe) based on the analysis of somatic mutation patterns.
      Our approach represents a fundamental advance over previous methods by shifting
      the problem from one of simply detecting selection to one of quantifying
      selection. Along with providing a more intuitive means to assess and visualize
      selection, our approach allows, for the first time, comparative analysis between
      groups of sequences derived from different germline V(D)J segments. Application
      of this approach to next-generation sequencing data demonstrates different
      selection pressures for memory cells of different isotypes. This framework can
      easily be adapted to analyze other types of DNA mutation patterns resulting from
      a mutator that displays hot/cold-spots, substitution preference or other
      intrinsic biases.

PMID- 22641857
TI  - Does consideration of psychopathy and sexual deviance add to the predictive
      validity of the static-99R?
AB  - The Static-99 is the most commonly used actuarial risk assessment tool for the
      prediction of sexual recidivism. In addition, the use of psychopathy and sexual
      deviance has been common in assessing sexual offenders, based on research
      suggesting that these factors have predictive validity. It has also become common
      practice to modify risk assessments based on the Static-99/99R because of the
      presence of psychopathy and indicators of deviant sexual interests, although to
      date there has been no research validating this procedure. The current research
      was conducted to fill this gap in the literature. Using a sample of 272 sexual
      offenders, the extent to which psychopathy, sexual deviance, and their
      interaction added to the predictive validity of the Static-99R was examined.
      Analyses were conducted using the whole sample as well as subgroups of rapists
      and child molesters. It was found that although the Static-99R predicted sexual
      recidivism, adding psychopathy and sexual deviance in a Cox regression analysis
      did not improve the prediction. This held true for child molesters when examined
      on their own. For rapists, although psychopathy and sexual deviance did not
      contribute to the prediction of sexual recidivism, for serious (i.e., violent
      including sexual) recidivism, the inclusion of psychopathy added to the
      prediction. Results are discussed in terms of implications for practice. 

PMID- 22641858
TI  - Understanding success and nonsuccess in the drug court.
AB  - The drug court was developed as a response to the ineffectiveness of the
      traditional criminal justice response to addiction. It has grown from 1 Miami
      court in 1989 to more than 2,100 drug court programs across the United States in
      2011. The drug court has been described as a restorative or community justice
      intervention that can benefit the offender, direct and indirect victims, and the
      community as a whole through its combination of treatment, intensive supervision,
      and regular court appearances. Although the number of qualitative drug court
      studies has increased in recent years, there are few studies that compare those
      who successfully complete the drug court program with those who do not complete.
      This article is a qualitative study of drug court participants in an Arkansas
      drug court program. The article compares and contrasts the perceptions of those
      graduated from the program with those who were terminated from the program. 

PMID- 22641859
TI  - An evaluation of a short-term drug treatment for jail inmates.
AB  - A total of 70 jail inmates who participated in an intensive, short-term drug
      treatment program were compared with a matched group of 70 jail inmates who did
      not participate in the program. Survival analysis was used to estimate the hazard
      of recidivism during 14 months following release from jail. The hazard ratio was
      significantly lower for the treatment than control group, and an analysis using
      propensity scores confirmed these results. Only 27% of the treatment participants
      were returned to jail or prison for more than 30 days, compared with 46% of the
      matched control group. According to qualitative responses from the participants,
      the program helped inmates recognize the consequences of their behavior and
      change their perspective. The results indicate that an intensive, short-term drug
      treatment program can be implemented within jails and might be a useful tool to
      help offenders prepare for reentry and reduce their risk of recidivism. 

PMID- 22641860
TI  - Age and type of onset of offending: results from a sample of male sexual
      offenders referred for civil commitment.
AB  - Sexual abuse research suggests that sexual offending is usually preceded by
      nonsexual offending, but little else is known or understood about the specific
      kinds of nonsexual crimes or patterns of crime that occur before serious sexual
      offending. The present study examined the official criminal histories of 751 men
      convicted of sexual offenses and referred to the Massachusetts Treatment Center
      for civil commitment. This relatively serious and chronic sample was arranged and
      compared with the type of their first officially recorded offense. Those whose
      first official charge was for a sexual offense ("sexual onset") were compared
      with nonsexual "violent onset" and "property onset" offenders. Important
      differences were detected between groups. Those with a property onset experienced
      more criminological risk factors and reflected the characteristics typical of
      chronic offenders. These results indicate that a more dedicated understanding of
      the beginning of one's criminal career is a beneficial direction for future
      study. 

PMID- 22641861
TI  - Heparin dosing is associated with diffusion weighted imaging lesion load
      following aneurysm coiling.
AB  - BACKGROUND AND PURPOSE: Diffusion weighted imaging (DWI) may be used to evaluate
      post-coiling ischemia. Heparinization protocols for cerebral aneurysm coiling
      procedures differ among operators and centers, with little literature surrounding
      its effect on DWI lesions. The goal of this study was to determine which factors,
      including heparinization protocols, may affect DWI lesion load post-coiling.
      MATERIALS AND METHODS: A review of 135 coiling procedures over 5 years at our
      centre was performed. Procedural data including length of procedure, number of
      coils used, stent or balloon assistance and operators were collected. Procedures
      were either assigned as using a bolus dose (>2000 U at any one time) or small
      aliquots of heparin (<=2000 U). Postprocedure DWI was reviewed and lesions were
      classified as small (< 5mm), medium (5-10 mm) or large (>10 mm). The cases were
      then classified into group 1 (<=5 small lesions) or group 2 (>5 small lesions or
      >=1 medium or large lesion). Multivariate regression of the procedural variables
      for the two groups was calculated. A p value of <0.05 was considered significant.
      RESULTS: There were 78 procedures in group 1 and 57 procedures in group 2.
      Patients who received small aliquots (n=37) versus boluses of heparin (n=98)
      intraprocedurally had significantly greater frequency and size of DWI lesions
      (p=0.03). None of the other procedural variables was found to impact on lesion
      load. CONCLUSIONS: More substantial DWI lesions were associated with small
      aliquots of heparin dosage compared with bolus doses. Heparin boluses should be
      preferentially administered during aneurysm coiling.

PMID- 22641862
TI  - Persistent vestige of dorsal ophthalmic artery: a case report.
AB  - A rare case of a persistent dorsal ophthalmic artery is reported. An elderly
      woman presented with subarachnoid hemorrhage and hydrocephalus. A CT angiogram
      revealed findings consistent with a small aneurysm and the presence of a dorsal
      ophthalmic artery. This was confirmed with catheter diagnostic angiography. The
      radiological findings, embryology and anatomy of these dual ophthalmic arteries
      are discussed.

PMID- 22641863
TI  - Surveillance imaging after intracranial stent implantation: non-invasive imaging
      compared with digital subtraction angiography.
AB  - BACKGROUND: Digital subtraction angiography (DSA) is the gold standard imaging
      for detection of in-stent restenosis (ISR) but there is limited literature on
      optimal non-invasive surveillance imaging. In this study, the ability of CT
      angiography (CTA) and MR angiography (MRA) compared with DSA in recognizing ISR
      was assessed. METHODS: A single center database of patients treated with stent
      implantation for ICAD was accessed. All patients who underwent follow-up imaging
      with DSA paired with either MRA or CTA within 30 days were included. Two
      angiography readers and two non-invasive imaging readers measured restenosis with
      a submillimeter digital caliper. ISR was categorized as: none/minimal, mild
      (<50%), moderate (>=50-70%) or severe (>=70%). Analysis was performed with
      weighted kappa statistics. RESULTS: 17 cases of individual stents that underwent
      surveillance imaging with paired DSA and CTA and five stents with paired DSA and
      MRA were identified. Of those undergoing DSA and CTA, inter-reader agreement
      produced kappa=0.68 (95% CI 0.40 to 0.95) for DSA and kappa=0.75 (95% CI 0.55 to
      0.95) for CTA. Agreement across CTA and DSA was kappa=0.36 (95% CI 0.26 to 0.52).
      Of those undergoing DSA and MRA, inter-reader agreement produced kappa=0.71 (95%
      CI 0.27 to 1.00) for DSA and kappa=1.00 (95% CI 1.00 to 1.00) for MRA. Agreement
      across MRA and DSA was kappa=0.34 (95% CI 0.18 to 0.51). CONCLUSIONS: Good inter
      reader agreement exists within DSA, CTA and MRA. However, when comparing non
      invasive imaging (CTA and MRA) with DSA, only fair agreement exists. These data
      suggest that CTA and MRA are not comparable to DSA for evaluation of ISR.

PMID- 22641865
TI  - Do e-cigarettes help smokers quit?

PMID- 22641866
TI  - Watch for these new generics.

PMID- 22641864
TI  - Lucja Frey (1889-1942): life destroyed by the Holocaust--on the 70th anniversary
      of her death.
AB  - Lucja Frey was the first to explain the pathogenesis of the auriculotemporal
      syndrome, and the syndrome is recognized today as the Frey syndrome. Patients
      with this disease are subjected to paroxysmal paraesthesia of half of the face
      combined with sweating and redness. This syndrome can be found in the
      differential diagnosis of contemporary dermatology. Among others, it is
      differentiated from food allergies. The life and scientific career of Lucja Frey
      was brutally interrupted by the tragic times of the Holocaust.

PMID- 22641868
TI  - Dangerous devices: most medical implants have never been tested for safety.

PMID- 22641870
TI  - Veterinary colleges focus  on economic concerns.

PMID- 22641869
TI  - Students tackle  financial challenges.

PMID- 22641871
TI  - WEVA in the world.

PMID- 22641872
TI  - Immune plasma  for treatment of  parvoviral gastroenteritis.

PMID- 22641873
TI  - Potassium bromide  products marketed for use  in dogs.

PMID- 22641874
TI  - The future of the veterinary  profession.

PMID- 22641875
TI  - [Face of misfortune].

PMID- 22641876
TI  - [Hepatic portal venous gas].

PMID- 22641877
TI  - [Lymphomas in children and adolescents].
AB  - Non Hodgkin lymphomas in the pediatric population are a heterogeneous group of
      tumors with distinct pathologic, immunologic and clinical characteristics. Over
      the past three decades, significant advancements have been made in the molecular
      characterization of these disorders. More than 90% of pediatric childhood non
      Hodgkin lymphomas are high grade lymphomas belonging to four major histologic
      subtypes, Burkitt lymphoma, diffuse large B-cell lymphoma, lymphoblastic lymphoma
      and anaplastic large cell lymphoma. With the use of intensive multiagent
      chemotherapy, most patients can now be cured and long-term event free survival is
      above 80% in most histologic subtypes. The identification of molecular events
      associated with carcinogenesis leads to the identification of novel targeted
      therapy which should allow a further improvement of treatment including a
      reduction of treatment burden in early stages and improvement of survival in
      advanced stages.

PMID- 22641878
TI  - [Cutaneous metastasis of lung cancer].

PMID- 22641879
TI  - [Radiation induced side effects].
AB  - More than half of all people with cancer are treated with radiation therapy. Over
      the last decade the technical advances, both in therapy beam precision and
      imaging, have greatly improved the therapeutic ratio and accuracy of modern
      radiotherapy. However, damaging healthy tissues near the tumor leads to radiation
      induced injury that develops immediately and continue to progress long after
      exposure to radiation. Recently dramatic advances have been made in understanding
      the determinant of tissue response to radiation exposure.

PMID- 22641880
TI  - [Tuberculosis. Shorten time to diagnosis].

PMID- 22641881
TI  - [Epidemiology of tuberculosis].
AB  - Tuberculosis is one of the leading causes of infectious disease worldwide, with
      an estimate of more than 8 million new cases each year. Tuberculosis notification
      rates have been decreasing since 2002, but some countries, in Asia and sub
      Saharan Africa, are still particularly affected. HIV co-infection and the
      emergence of resistant strains warrant further efforts to improve tuberculosis
      control worldwide. France is considered as a low incidence country but important
      disparities between populations and territories exist. Thus, the elderly, those
      living in large cities or in socio-economic deprived condition and persons born
      in high-endemic countries are mostly affected. The national tuberculosis program
      was launched in 2007, aiming at reducing these disparities.

PMID- 22641882
TI  - [Who should have the BCG vaccine? When?].

PMID- 22641884
TI  - [Tuberculosis contact investigation].

PMID- 22641883
TI  - [The natural story of tuberculosis].
AB  - Tuberculosis is one of the infectious diseases that had a huge impact on the
      health of the populations since the XVIIth century, and this remains true for
      most of the people in the World in 2012. Its natural story involves:
      contamination (inhalation of infectious particles, the Pflugge droplets,
      originating from a patient with bacillary tuberculosis); primary infection
      (remarkable by initial unresponsiveness of the immune system, followed by strong
      cellular immunity development within 3 to 9 weeks); latent tuberculosis
      infection, non-contagious and totally asymptomatic, with efficient control of
      tuberculosis bacilli replication, lasting for life in more than 90% of cases; and
      less frequently, tuberculosis disease in patients with insufficient immunity,
      including children less than 5 years, immunocompromised, and patients recently
      infected.

PMID- 22641885
TI  - [What causes diagnosis delay in tuberculosis?].

PMID- 22641886
TI  - [Bacteriological diagnosis of tuberculosis].
AB  - Today, microscopic examination and culture are still essential for active
      tuberculosis diagnosis and therapeutic decisions. Nucleic acid amplification and
      line probe assays speed up identification and susceptibility testing of
      mycobacteria in AFB smear positive specimens or in culture. They are also
      efficient for comparison of M. tuberculosis strains with each other (genotyping).
      On the other hand, today, molecular tests are not relevant for the diagnosis in
      smear negative specimens and even more for diagnosis of culture-negative
      tuberculosis.

PMID- 22641887
TI  - [IGRA tests in clinical practice].

PMID- 22641888
TI  - [Tuberculosis treatment in adults].
AB  - The quadritherapy by isoniazid, rifampicin, pyrazinamide and ethambutol, is still
      the gold standard for the treatment of tuberculosis disease. Except for severe
      presentations, the treatment remains based on a 6 months therapy with a 2 months
      induction phase. During the first health care contact, looking for an
      immunosupression and risk factors of hepatotoxicity and multiresistant strains is
      necessary. A close supervision by medical staff is recommended during all
      treatment duration. Rifampicin expose to drug interactions. In France, once the
      diagnosis is made, the referent practitioner and the biologist must notify the
      case to the local Health Authorities which is in charge of finding and treat, if
      needed, the newly infected case contacts. In order to prevent transmission, a
      respiratory isolation must be performed for smear positive patients. In case of
      renal or hepatic previous impairment, a multidisciplinary and closely supervision
      is recommended. Treatment of extensively and multi drug resistant (MDR)
      tuberculosis is based on combination of 2nd line drugs, and a prolonged treatment
      is advised. Expert supervision is necessary for case management.

PMID- 22641889
TI  - [Treatment of latent tuberculosis infection].

PMID- 22641890
TI  - [Paradoxical response during antituberculosis therapy].

PMID- 22641891
TI  - [Characteristics of tuberculosis in children].

PMID- 22641892
TI  - [Organization of tuberculosis control in France in 2011].

PMID- 22641893
TI  - [Epidemiology of infective endocarditis].
AB  - In industrialized countries, after the eradication of rheumatic fever, rheumatic
      valve diseases progressively disappeared and the proportion of post-rheumatic
      infective endocarditis significantly decreased. Intravenous drug use, prosthetic
      valves, age-related degenerative valve sclerosis, and invasive procedures have
      become the most important risk factors for infective endocarditis. These changes
      resulted in a decreased incidence of streptococcal endocarditis and an increased
      incidence of staphylococcal endocarditis.

PMID- 22641895
TI  - [Diagnostic approach to infectious endocarditis].
AB  - Major advances in imaging and microbiological procedures have changed the
      diagnostic approach of infective endocarditis. New imaging tools have improved
      the search of local complications, systemic embolism and diagnosis of infection
      of cardiac devices. Moreover, microbiological diagnosis has been transformed by
      molecular techniques as long as these procedures have highlighted microorganisms
      thus far neglected by classical techniques. Despite these advances, endocarditis
      remained a clinical diagnosis which still depends on a high index of clinical
      suspicion.

PMID- 22641894
TI  - [Is infective endocarditis prophylaxis always recommended?].
AB  - Infective endocarditis prophylaxis is a preventive strategy that has been
      recommended in various countries for more than 50 years. It is based on the
      plausible assumption that infectious endocarditis is, at least partially,
      avoidable. Traditionally, prophylaxis has consisted in the administration of an
      antibiotic agent in subjects with high-risk heart disease, or before high-risk
      interventions. More than 20 years ago, the indications of antibiotic prophylaxis
      were reduced and limited to high-risk patients and interventions, essentially
      valve replacement, or dental procedures with mucosal involvement, while the
      recommendations for overall non-antibiotic preventive measures, as well as
      recommendations for earlier diagnosis, have been reinforced.

PMID- 22641896
TI  - [Antibiotherapy of infectious endocarditis].
AB  - Antibiotherapy is the pillar of the infectious endocarditis treatment.
      Bactericidal drugs must be used and their choice has to be adapted to bacterial
      sensitivity. The duration of treatment, traditionaly lengthy, especially in
      prosthetic valve endocarditis, depends on bacteria and has been shortened in some
      guidelines because of the combination of aminoglycoside.

PMID- 22641897
TI  - [To outpatient treatment of infective endocarditis?].

PMID- 22641898
TI  - [Surgery for infective endocarditis].
AB  - Surgical treatment is a cornerstone in the management of infective endocarditis,
      approximately 50% of patients should be operated in the acute phase. Surgery is
      indicated in heart failure by acute valvular insufficiency refractory to medica
      treatment, persistent sepsis despite adequate antibiotic therapy, infections by
      microorganisms with low response to antibiotics, paravalvular abscess or cardiac
      fistulas, and for prevention of cerebral embolism when large vegetations are
      present. Other indication in prosthetic valve endocarditis is prosthesis
      dysfunction including significant perivalvular leaks or obstruction. In infection
      of leads of electrophysiological cardiac devices material should always be
      removed, preferably percutaneously, surgery is indicated when it is not
      technically possible.

PMID- 22641899
TI  - [PubMed in 10 lessons: no 4. The method MeSH database + limits].

PMID- 22641900
TI  - [The patient's voice].

PMID- 22641901
TI  - [What treatment of isolated fever in the child?].

PMID- 22641902
TI  - [Screening orthopedic abnormalities in children: age is important].

PMID- 22641903
TI  - [Radiculalgies and nerve entrapment syndromes].

PMID- 22641904
TI  - [Malignant lymphoma].

PMID- 22641905
TI  - [Acute anxiety and panick attack].

PMID- 22641907
TI  - [Raynaud's phenomenon].

PMID- 22641906
TI  - [Cardiac arrest].

PMID- 22641909
TI  - Winning by a hair--MU journalism professors agree: Missouri Medicine best article
      of 2009.

PMID- 22641908
TI  - [The progressive humanization of intensive care].

PMID- 22641910
TI  - Bringing bad news to the public.

PMID- 22641911
TI  - Why 'quality' care is dangerous.

PMID- 22641912
TI  - Missourians face risk in counterfeit medicines.

PMID- 22641913
TI  - Prevention of acute myocardial infarction by physician community activism.

PMID- 22641914
TI  - Making a personal connection in the medical interview.
AB  - The medical interview is an access point for contacting patients at the core of
      their being. Patients with concernfull medical problems initially and
      unreflectively grasp these conflicted situations directly in terms of their
      meaning for the self. The situation and the self can become fused transparently.
      Physicians can facilitate patients awareness of their core self which is separate
      from their medical issue, by creating an opportunity for patients to experience
      the core of being that they mutually share. In the medical interview the
      possibility of making a personal connection with the patient is already present
      in the context of the presupposed shared history of a caring relationship between
      patients and physicians. The physician's gift of presence, of riveted attention
      and silence as the patient describes her concerns, can create an opening for
      awareness of their mutual involvement in a common web of concerns at a profound
      level. Being attuned initially can be reinforced by attending to perceptual
      domains. The hearing that listens and the seeing that can result in vision can
      allow for inspiration. Touching with gentleness is a primal mode of knowing and
      understanding. Words themselves can have great salutary power. Who has not
      wondered at the "tingle" that occurs during the reading of a powerful poem? What
      if you do make a personal connection with patients? What if you don't? Even
      though there is little scientific evidence or statistics to ground the assertion
      that there is value in a profound relationship I maintain that it is a way to
      follow the path you have chosen. It is the distinction between a job and a
      calling. It also lightens the burden we carry in our continual conflict with the
      increasing pressure of technology, third parties, and the other which is 'other.'
      Making a personal connection with patients is not about the "trickle down" of
      humanity from physicians to patients. Personal connection is inspiring to
      physicians and patients and enlightening and empowering. Imagine yourself
      connecting daily with patients at a meaningful level to get their health concerns
      handled and then another and then another. Doing otherwise creates tiredness and
      burnout. Connection even for a brief moment produces the powerful enchantment of
      presence for patients and physicians.

PMID- 22641915
TI  - State of MSMA--presidential address.

PMID- 22641916
TI  - Put the "we" in organized medicine.

PMID- 22641917
TI  - The initial evaluation of the diabetic foot ulcer.
AB  - This article is a comprehensive clinical review of the initial evaluation of
      diabetic foot disease.

PMID- 22641918
TI  - A collaborative skin cancer educational program for adolescents.

PMID- 22641919
TI  - Elective primary cesarean section: weighing the risks and benefits.
AB  - The increasing understanding of the nature and extent of pelvic floor injury
      during childbirth, coupled with an increasing medico-legal demand to present a
      flawless baby at the completion of the birth process, has helped fuel the rising
      cesarean section rate. As more women become educated in the controversies
      surrounding the protective benefits of cesarean, they may increasingly elect to
      undergo cesarean delivery primarily. Evidence concerning maternal, fetal, and
      ethical considerations in this decision is presented.

PMID- 22641920
TI  - Newborn metabolic screening and related pitfalls.
AB  - Newborn screening has recently been transformed by our enhanced knowledge of
      medical disorders and our ability to detect and manage them. The Missouri State
      Newborn Screening Laboratory incorporated tandem mass spectrometry into the
      newborn screening protocol in 2005. This review will highlight the new
      capabilities of the newborn screening laboratory and the pitfalls of screening
      related to preterm birth, blood transfusion and intravenous fluid administration
      that complicate the interpretation of screening results.

PMID- 22641921
TI  - Effect of conjugated linoleic acid on proliferation and cytokine expression of
      bovine peripheral blood mononuclear cells and splenocytes ex vivo.
AB  - Twenty-five primiparous Holstein cows were divided into five experimental groups
      (five animals per group) by different feeding (control fat preparation [CON] or
      conjugated linoleic acid [CLA] supplement) and slaughtering times. The daily
      consumption of CLA was 6.0 g of the trans-10, cis-12 CLA-isomer and 5.7 g cis-9,
      trans-11 CLA isomer. An initial group (IG) was slaughtered one day post partum
      (pp) and the remaining 20 animals after 42 and 105 days pp, respectively. Blood
      for peripheral blood mononuclear cells (PBMC) separation was taken seven days
      ante partum and immediately before slaughter. The spleen was removed during
      dissection for isolation of splenocytes and samples for histopathological
      examination. Cell viability and Concanavalin A-stimulated proliferation was
      analysed by MTT and Alamar Blue assay. Basal expression of cytokines (interleukin
      [IL]-4, IL-10, IL-12, tumour necrosis factor alpha [TNF-alpha] and interferon
      gamma [IFN-gamma]) was measured by quantitative real time polymerase chain
      reaction (qRT-PCR) in unstimulated PMBC and splenocytes. With PBMC, stimulation
      indices increased from 1 day pp to 105 days pp with no differences between CLA
      and CON groups. With splenocytes, the stimulation index of the CLA group was
      lower compared to CON group 105 days pp. Baseline expression of cytokines was not
      effected by CLA feeding comparing similar time points. Also, no differences
      occurred in the expression of IL-4 in PBMC and IL-10 as well as TNF-alpha in both
      cell populations, when comparing the feeding groups separately with IG. IL-4 was
      more frequently expressed in CLA group 42 days pp in splenocytes. IFN-gamma
      expression was increased 105 days pp in CLA group in splenocytes and PBMC. IL-12
      was higher expressed 105 days (PBMC) or 42 days pp (splenocytes) when compared to
      IG. There was no effect of CLA feeding or slaughter time on histopathology of the
      spleen. In conclusion, the present results demonstrate an inhibiting effect of
      CLA on the mitogen-induced activation of splenocytes.

PMID- 22641922
TI  - Effect of dietary fibre on nitrogen retention and fibre associated threonine
      losses in growing pigs.
AB  - Apart from being an energy source, dietary fibre is also discussed to act as anti
      nutritional factor reducing apparent precaecal protein and amino acid (AA)
      digestibility due to reduced absorption or increased endogenous secretion or
      both. However, the amounts of protein and AA of endogenous origin determined at
      the terminal ileum in cannulated animals do not represent the total losses
      associated with endogenous secretion. A high proportion of secreted protein is
      reabsorbed and does not reach the terminal ileum, and losses occur during
      synthesis of endogenous protein. Therefore, the present study used an alternative
      indirect approach, taking the reduction of nitrogen (N) retention in a threonine
      (Thr) limited diet as a sensitive indicator for fibre-associated Thr losses. Two
      experiments were conducted with 12 castrated male pigs each between 37 and 75 kg
      body weight to measure the effect of the intake of Thr and 150 and 300 g/d fibre
      from wheat bran (Exp. 1), or 150 g/d fibre from rape seed, cassava leaves, and
      cassava root peels, respectively (Exp. 2), on N retention. During two (Exp. 1)
      and three (Exp. 2) balance periods the animals were subjected to the dietary
      treatments according to a cross-over design. All animals received 1350 g/d of a
      wheat-soybean-based diet supplemented with free AA to ensure Thr being the first
      limiting AA. To determine the effect of Thr on N retention, intake of the basal
      diet was reduced to 1150 g/d and supplemented with corn starch to reach equal
      energy intake and an unchanged AA pattern. With increasing BW additional starch
      was added to all diets to ensure a constant energy intake of 1.25 MJ ME/kg
      BW(0.75). Since the fibre sources contained small amounts of Thr, N retentions
      were corrected for precaecal digestible Thr intake originating from the fibre
      sources according to the Thr effect on N retention as determined in experiment 1.
      Corrected N retentions were affected by fibre level (p = 0.007) and source (p <
      0.001). Fibre-associated Thr losses amounted to 3.3, 3.2, 1.2, and 1.1 g/kg fibre
      from wheat bran, rapeseed, cassava leaf, and cassava root peel, respectively. It
      is concluded that Thr losses per gram of dietary fibre depend on the fibre source
      and that fibre concentration and source in pig diets should be considered as a
      factor affecting Thr requirement.

PMID- 22641923
TI  - Effects of sodium butyrate and salinomycin upon intestinal microbiota, mucosal
      morphology and performance of broiler chickens.
AB  - The effect of dietary sodium butyrate (SB) or salinomycin (SAL) or both additives
      on performance, small intestinal morphology and microbial ecology of broiler
      chickens was studied. A growth trial was conducted with 96 Ross 308 female
      broilers from 1 to 30 days of age. Four treatment groups were fed with a non
      supplemented control diet or three experimental diets supplemented with i) 300 mg
      SB (Adimix 30 coated) per kg, ii) 60 mg SAL (Sacox) per kg or iii) both additives
      in combination. Feed intake and body-weight gain decreased and gain-to-feed ratio
      increased due to SAL supplementation, while addition of SB did not affect
      performance in comparison with the control diet but positively affected feed
      intake and body-weight gain in comparison with birds fed the SAL-supplemented
      diet. Villus height in jejunum decreased, while crypt depth increased due to SAL
      supplementation. Addition of SB increased crypt depth in jejunum. No significant
      effect of either additive was observed in ileum morphology. Total short-chain
      organic acids concentration in ileal digesta decreased with SAL supplementation,
      mainly due to lower lactic acid concentration, but no effects were observed in
      the caeca. The SAL supplementation was accompanied by a pH increase in ileum and
      a pH decrease in caecum. No significant effect of SB addition was observed for
      these parameters. Total bacterial numbers and Lactobacillus [lactic acid bacteria
      (LAB)] counts in ileal and caecal contents were lower in birds fed with SAL
      supplemented diet in comparison with birds fed with control or SB diet. DNA
      fingerprints revealed SAL supplementation to affect the microbial population by
      suppressing dominating LAB, potentially L. aviarius. The presented results show
      that dietary SAL, supplemented alone or in combination with SB, suppressed the
      microbial activity and altered the microbial community structure mainly in ileum.
      SAL alone negatively affected feed intake and body-weight gain; however, the
      effect was ameliorated by SB supplementation.

PMID- 22641924
TI  - Effect of wheat distillers' grains with solubles and a feed flavour on
      performance and carcass traits of growing-finishing pigs fed wheat and canola
      meal based diets.
AB  - Forty-eight crossbred pigs were assigned to one of six dietary treatments in a 6
      x 2 (treatment x sex) factorial arrangement. Diets were based on wheat and canola
      meal and were formulated to contain 0%, 4.9%, 9.7%, 14.6% or 19.4% wheat
      distillers' dried grains with solubles (DDGS) during the growing period and 0%,
      4.0%, 8.1%, 12.1% and 16.1% wheat DDGS during the finishing period. The addition
      of wheat DDGS was made at the expense of both wheat and canola meal. A feed
      flavour was added to the diet in which wheat DDGS supplied 100% of the
      supplementary protein. Over the entire experimental period (21.5-112.2 kg),
      increasing the level of wheat DDGS resulted in a linear decrease in weight gain
      and feed conversion ratio. Feed intake was linearly reduced by inclusion of wheat
      DDGS during the growing period (21.5-57.4 kg) but not the finishing period (57.4
      112.2 kg). Increasing the level of wheat DDGS in the diet resulted in a linear
      decline in carcass value index and lean yield while loin fat linearly increased.
      The addition of a flavour to the diet in which DDGS supplied 100% of the
      supplementary protein had no effect on performance or carcass traits.

PMID- 22641925
TI  - Effects of wheat dried distillers' grains with solubles and cinnamaldehyde on in
      vitro fermentation and protein degradation using the Rusitec technique.
AB  - This study was conducted to evaluate the effect of wheat dried distillers' grains
      with solubles (DDGS) and cinnamaldehyde (CIN) on in vitro fermentation and
      microbial profiles using the rumen simulation technique. The control substrate
      (10% barley silage, 85% barley grain and 5% supplement, on dry matter basis) and
      the wheat DDGS substrate (30% wheat DDGS replaced an equal portion of barley
      grain) were combined with 0 and 300 mg CIN/l of culture fluid. The inclusion of
      DDGS increased (p < 0.05) the concentration of volatile fatty acids (VFA) and the
      molar proportion of acetate and propionate. Dry matter disappearance (p = 0.03)
      and production of bacterial protein (p < 0.01) were greater, whereas the
      disappearances of crude protein (CP) and neutral detergent fibre were less (p <
      0.01) for the DDGS than for the control substrate. With addition of CIN,
      concentration of total VFA decreased and fermentation pattern changed to greater
      acetate and less propionate proportions (p < 0.01). The CIN reduced (p < 0.01)
      methane production and CP degradability. The copy numbers of Fibrobacter,
      Prevotella and Archaea were not affected by DDGS but were reduced (p < 0.05) by
      CIN. The results indicate that replacing barley grain by DDGS increased nutrient
      fermentability and potentially increase protein flows to the intestine.
      Supplementation of high-grain substrates with CIN reduced methane production and
      potentially increased the true protein reaching the small intestine; however,
      overall reduction of feed fermentation may lower the feeding value of a high
      grain diet.

PMID- 22641926
TI  - Highly deoxynivalenol contaminated oats and immune function in horses.
AB  - The aim of the present study was to investigate the impact of deoxynivalenol
      (DON) on cellular and humoral immune parameters in horses. A feeding trial using
      naturally contaminated oats with high (20.2 mg/kg) and low (0.49 mg/kg) levels of
      DON was conducted. Two groups of five mares were fed 2 kg oats daily with high or
      low DON levels for two weeks, using a crossover design with a three-week wash-out
      period. No adverse effects on general health were observed. Only minor diet
      related changes in differential blood counts and serum biochemistry were noted.
      Serum haptoglobin concentration was significantly elevated after feeding DON (p =
      0.04). Lymphocyte subsets (CD4+ CD8+, CD2+, CD21+, MHCII+) and lymphocyte
      proliferation data (concanavalin A, phytohemagglutinin, pokeweed mitogen) were
      not different between feeding-groups. It can be concluded that daily DON intakes
      as high as 6.9 to 9.5 mg/100 kg BW appear to have no major impact on the measured
      immune response of horses, indicating that this species has a high tolerance for
      DON.

PMID- 22641927
TI  - Associations between plasma cytokines and depressive mood in patients with breast
      cancer.
AB  - OBJECTIVE: The few studies on the associations between cytokines and depressive
      mood in patients with cancer have produced conflicting results. This study
      investigated the associations between plasma cytokines and depressive mood in
      patients with breast cancer using a large panel of pro-inflammatory, anti
      inflammatory, and immune-modulating cytokines. METHODS: We recruited 273
      hospitalized patients with breast cancer awaiting surgery. Preoperative plasma
      samples were obtained for cytokine analysis, including pro-inflammatory
      (interleukin [IL]-2, IL-12, interferon [IFN]-gamma, and tumor necrosis factor
      [TNF-alpha]), anti-inflammatory (IL-4, IL-5, IL-10, and IL-13), and immune
      modulating (granulocyte/macrophage colony-stimulating factor [GM-CSF]) cytokines.
      Depressive mood was measured using the Montgomery-Asberg Depression Rating Scale
      (MADRS) at 2-5 days postoperatively, when the patients could cooperate.
      Covariates included various demographic and clinical characteristics. The
      association between the MADRS score and each cytokine level was estimated using
      linear regression models. RESULTS: Cytokine levels were significantly inter
      correlated. Depressive mood was associated with lower levels of pro-inflammatory
      (IL-2, IL-12, and TNF-alpha), anti-inflammatory (IL-5, IL-10, and IL-13), and
      immune-modulating (GM-CSF) cytokines independent of potential covariates such as
      living area or functional level. CONCLUSIONS: The findings suggest that
      depressive mood is associated with a generally decreased inflammatory reaction or
      immune function in patients with breast cancer.

PMID- 22641928
TI  - Living arrangements and risk for late life depression: a meta-analysis of
      published literature.
AB  - OBJECTIVE: The goal of this study was to determine the relationship between
      living arrangements and risk for depression among older people. METHOD: MEDLINE,
      EMBASE, The Cochrane Library database was used to identify potential studies. The
      studies were divided into cross-sectional and longitudinal subsets. Qualitative
      meta-analysis of the cross-sectional studies and longitudinal studies was
      performed, respectively. For prevalence and incidence rates of depression, odds
      ratio (OR) and relative risk (RR) were calculated, respectively. RESULTS: The
      qualitative meta-analysis showed that older people living alone had a higher risk
      of depression than those not living alone (OR: 1.44; 95% confidence interval [95%
      CI]: 1.04-1.99); Relative risk (RR: 1.27, 95% CI: 0.89-1.80) and those living
      with families (OR: 2.59, 95% CI: 1.60-4.20). Older people living in a nursing
      home (OR: 2.90, 95% CI: 0.94-8.94; RR: 1.94, 95% CI: 1.18-3.20) or
      institutionalized setting (OR: 1.86, 95% CI: 1.37-2.52; RR: 2.03, 95% CI: 1.12
      3.70) had a higher risk of depression than those living in home. CONCLUSIONS:
      Despite the methodological limitations of this meta-analysis, living arrangements
      appear related to the risk for depression in the older population. Older persons
      living alone, in a nursing home, or in an institutionalized setting have higher
      risk for depression.

PMID- 22641929
TI  - Health-related quality of life and its determinants in the urban Russian
      population with major depressive disorder: a cross-sectional study.
AB  - OBJECTIVE: Depressive disorders pose a major challenge to healthcare in the
      countries of the former Soviet Union. The objective of the current study was to
      evaluate health-related quality of life (HrQoL) and its determinants in
      outpatients with major depressive disorder in an urban Russian population.
      METHODS: We consecutively recruited 100 urban Russian outpatients with major
      depression and 100 non-depressed controls who were matched for age and sex. The
      severity of their depression was assessed using the Hamilton Depression Rating
      Scale (HDRS). HrQoL was evaluated using the EuroQol (the EQ-5D and the visual
      analogue scale, EQ VAS). Independent determinants of HrQoL were identified using
      multiple regression analysis. RESULTS: The mean EQ VAS score was 43.0 +/- 27.4 in
      patients with depression compared to 81.4 +/- 14.7 in the controls (p < 0.01).
      Out of the domains of the EQ-5D, "anxiety/depression," "usual activities," and
      "self-care" were the most impaired. Independent determinants of reduced HrQoL
      were: severity of depression according to the HDRS; violent suicide attempts;
      suicide attempts in the past; and drug addiction. CONCLUSIONS: HrQoL is
      considerably reduced in Russians with major depression. The disease-specific
      patterns of HrQoL impairment and the independent determinants of HrQoL identified
      in our study could be addressed in focused healthcare programs and clinical
      trials. Comorbid drug addiction as a determinant of HrQoL should receive greater
      attention in the management of depressive disorders in urban Russian populations.

PMID- 22641930
TI  - Disability in a community population with MS with and without mental disorders.
AB  - OBJECTIVE: Psychiatric conditions are known to have a detrimental impact on
      functioning and may therefore influence patterns of disability associated with
      MS. Population-based studies are needed to evaluate such interactions. The
      objective of this study was to describe the pattern of interaction of MS and
      mental disorders on health-related impairments. METHODS: The Participation and
      Activity Limitation Survey (PALS) was a post-censual survey conducted by
      Statistics Canada in association with the 2006 Canadian Census. PALS collected
      detailed data from a random sample of n = 28,640 respondents with health-related
      impairments reported on their census form. The PALS interview collected self
      reported diagnostic data and included scales to assess functioning and
      participation in society. RESULTS: PALS identified 245 individuals with MS,
      leading to an estimated (weighted) population prevalence of 0.2% (200 per
      100,000), consistent with other Canadian estimates. As expected, impaired
      agility, vision, communication, mobility, pain, and memory were strongly
      associated with MS. Mental disorders were also associated with impairment, but
      interactions between these conditions and MS were generally not evident.
      CONCLUSIONS: Mental disorders are associated with a higher level of disability in
      MS but, with the exception of communication, there was no evidence of synergistic
      interaction between mental disorders and MS in contributing to health-related
      impairments.

PMID- 22641932
TI  - The effect of prayer on depression and anxiety: maintenance of positive influence
      one year after prayer intervention.
AB  - OBJECTIVE: To investigate whether the effect of direct contact person-to-person
      prayer on depression, anxiety, and positive emotions is maintained after 1 year.
      DESIGN, SETTING, AND PARTICIPANTS: One-year follow-up of subjects with depression
      and anxiety who had undergone prayer intervention consisting of six weekly 1-hour
      prayer sessions conducted in an office setting. Subjects (44 women) completed
      Hamilton Rating Scales for Depression and Anxiety, Life Orientation Test, and
      Daily Spiritual Experiences Scale after finishing a series of six prayer sessions
      and then again a month later in an initial study. The current study reassessed
      those subjects with the same measures 1 year later. One-way repeated measures
      ANOVAs were used to compare findings pre-prayer, immediately following the six
      prayer sessions, and 1 month and again 1 year following prayer interventions.
      RESULTS: Evaluations post-prayer at 1 month and 1 year showed significantly less
      depression and anxiety, more optimism, and greater levels of spiritual experience
      than did the baseline (pre-prayer) measures (p < 0.01 in all cases). CONCLUSIONS:
      Subjects maintained significant improvements for a duration of at least 1 year
      after the final prayer session. Direct person-to-person prayer may be useful as
      an adjunct to standard medical care for patients with depression and anxiety.
      Further research in this area is indicated.

PMID- 22641933
TI  - Use of templates for clinical documentation in psychiatric evaluations-beneficial
      or counterproductive for residents in training?
AB  - In psychiatry, as in other disciplines, electronic templates are replacing
      handwritten records to meet health care financing regulations and requirements of
      third-party payers. We address whether these checklists are helpful for
      residents, especially those beginning training, in learning the foundational
      skills of their discipline and in recording a comprehensive set of patient data.
      An informal survey of our residents suggests that residents find the templates
      useful, though they have advantages and disadvantages. We also review relevant
      literature from psychiatry and other fields on the use of electronic templates
      and pose questions about how we might gauge the usefulness of the templates in
      residents' training and in obtaining valid data for clinical decision-making.

PMID- 22641931
TI  - Effects of depression and social support on comprehension and recall of informed
      consent information among Parkinson disease patients and their caregivers.
AB  - OBJECTIVE: Relatively little attention has focused on the impact of psychiatric
      conditions on human subjects' comprehension of consent information. The purpose
      of this randomized study was to determine whether depression affects
      comprehension and recall of informed consent information among persons with
      Parkinson's disease and their caregivers and to evaluate the effects of support
      on comprehension and recall during the consent process. METHOD: Comprehension and
      recall of information were assessed using a modified version of the Modified
      Quality of Informed Consent Questionnaire, taken 1 week and 1 month later, and
      scored using a consensus-based algorithm. Participants also completed the Center
      for Epidemiologic Studies Depression Scale. Data analyses were conducted on 129
      patients and caregivers (t-tests, Fisher's exact tests, and ANCOVAs). RESULTS: T
      tests showed no significant differences in comprehension and recall between
      depressed and nondepressed participants at 1 week and 1 month. However, ANCOVA
      showed patients with a support person present had significantly higher
      comprehension and recall at 1 week but not at 1 month compared with controls.
      Caregivers present with a patient had lower comprehension/recall than those
      without a patient present (p = 0.02). CONCLUSIONS: Having a support person
      present during the informed consent process helps depressed PD patients better
      retain information in the short-term, but effects diminish over the long-term.
      Implications for interventions will be discussed.

PMID- 22641934
TI  - [A man unlike the others].

PMID- 22641935
TI  - [The nursing profession is experiencing a grand evolution].

PMID- 22641936
TI  - [Nurse consultation in wound healing clinics].
AB  - Projects for nurse-led wound healing clinics have aroused a growing interest over
      recent years, usually initiated by professionals with a university degree diploma
      in order to offer patients quality of care. The setting up of a nurse outpatient
      clinics cannot be a spur-of-the-moment act, as it involves prior reflection with
      regard to medical collaboration, available resources and activity assessment.

PMID- 22641938
TI  - [Patient education. Paradigm change and a reformed approach to care].

PMID- 22641937
TI  - [The prevention of pain during botulinum toxin injections in children].
AB  - According to the recommendations of the French health products safety agency
      (AFSSAPS) in 2009, botulinum toxin injections are recommended to reduce
      spasticity in children with cerebral palsy. Apprehension of the session can
      increase the pain. Therefore, programmes have been put in place which help to win
      over the child and gain their trust. Since 2008 a nurse consultation which
      informs the child through play has been set up in the centre for physical
      medicine and rehabilitation of the Association for the social and professional
      integration of disabled people.

PMID- 22641939
TI  - [Patient education, from implicit nursing practice to structured programs].
AB  - Therapeutic patient education, which with the "Hospital, patients, health and
      territories" law became a priority of the healthcare system, notably for chronic
      diseases, has been rooted in nursing training and practice since the 1960s.
      Following in the steps of the World Health Organisation and the International
      Council of Nurses, successive laws relating to the profession have continuously
      emphasised it. Now that it has an official and general framework in France, it
      should develop within nursing practice.

PMID- 22641940
TI  - [Patient education, facilitating its implementation and its assessment].
AB  - Therapeutic education, facilitating its implementation and its assessment.
      Therapeutic education programmes (TEP) must conform to national specifications
      and be self-assessed each year by the teams which implement them. On the basis of
      its previous work, the French national authority for health has published a
      guide, tested in the field, which specifies the framework of this approach.

PMID- 22641941
TI  - [Coordination and promotion of policies favoring patient education].
AB  - In the framework of therapeutic patient education (TPE), the definition of the
      actors' skills is an issue of growing importance. Work in this area has recently
      been carried out by the French national institute for prevention and health
      education (INPES).This work highlights a function which is seldom documented in
      literature: the coordination of TPE policies.

PMID- 22641942
TI  - [Patient education and regional healthcare requirements].
AB  - In the Pays de la Loire, only 3% of patients suffering from a long-term condition
      have access to a therapeutic education programme (TEP), mainly implemented in
      hospitals. A campaign is underway to promote the development of therapeutic
      education programmes on a regional level, notably by raising awareness of its
      benefits and coordinating the offer in cooperation with primary care workers and
      those working in the social sector. The aim is to improve patients' quality of
      life and to reduce repeated hospitalisations by providing "keys" for the
      preservation of patients' health status.

PMID- 22641943
TI  - [Implementing a patient education program in an outpatient health center].
AB  - Freelance health professionals have been brought together around a healthcare
      project which they created forming an outpatient multi-disciplinary team and
      health centre. This new organisation favours the recognition and remuneration of
      a new field of skills: the therapeutic education of patients suffering from
      chronic diseases.This new care is only provided after the professionals have
      received relevant training and in accordance with various constraints defined by
      law.

PMID- 22641944
TI  - [Creating and implementing a patient education program].
AB  - The nursing team of the medicine and diabetology unit of the inter-municipal
      hospital of Meulan-les-Mureaux has created a therapeutic patient education (TPE)
      programme. Its implementation is the result of a rewarding and constructive
      process for the nursing teams. It involved reflexive analysis with regard to
      their practices and encouraged team cohesion thanks to common objectives. TPE
      offers patients personalised treatment with a view to making them more autonomous
      and enabling them to become the player in the care of their pathology.

PMID- 22641945
TI  - [Education of heart failure patients].
AB  - Therapeutic patient education (TPE) has proved to be beneficial in a number of
      chronic diseases such as diabetes, asthma, chronic kidney failure. A TPE unit has
      been set up in Marie-Madeleine hospital in Forbach. In order to improve the
      actions carried out with patients with heart failure undergoing treatment, a
      satisfaction survey was carried out with this group of patients.

PMID- 22641946
TI  - [Patient education in psychiatry].
AB  - A nursing team from the day hospital of the Paris association for mental health
      assistance has been providing multi-disciplinary care to patients presenting
      serious personality disorders. For more than 10 years it has carried out action
      aimed at improving treatment compliance which is recognised in the framework of a
      therapeutic patient education programme.

PMID- 22641947
TI  - [A clinical monitoring tool for diabetic patients for the benefit of freelance
      nurses].
AB  - The major role in prevention and therapeutic education played by freelance nurses
      is essential in the face of the prevalence of diabetes in Reunion.This role can
      only be developed using multi-disciplinary and shared clinical monitoring tools.
      A growing number of freelance nurses are using a newly created traceability
      sheet,specifically designed to reflect those requirements.

PMID- 22641948
TI  - [The new nursing curriculum for the benefit of patient education].
AB  - Therapeutic patient education (TPE) imposes a radical change in the nurse-patient
      relationship. It is a real humanist trend whose values are taken up in the new
      nursing curriculum. Several teaching units are participating in the development
      of skill 5: Initiating and implementing educational and preventative care". This
      new element in the training programme is leading to real cultural evolution in
      professional practice.

PMID- 22641949
TI  - [Patient education and the patient care team, what role does the nurse take in
      each? ].

PMID- 22641950
TI  - [Bibliography. Patient education].

PMID- 22641951
TI  - [Grounded theory and nursing research].
AB  - Grounded theory is a methodology widely used in human and social sciences as well
      as nursing science. It is based on an inductive approach applied to data gathered
      in the field and which aims to offer an explanation of the phenomenon studied.The
      theorisation is a preliminary stage enabling care procedures to be developed and
      to be tested through research, with the aim of acting positively on the
      phenomenon.

PMID- 22641952
TI  - [Fundamental concepts of patient education].

PMID- 22641953
TI  - Penile cancer. Introduction.

PMID- 22641954
TI  - New pathologic entities in penile carcinomas: an update of the 2004 world health
      organization classification.
AB  - Most primary malignant tumors of the penis are squamous cell carcinomas (SCC) of
      the usual type. In recent years several variants, each with distinctive
      clinicopathologic features, have been described. Pseudohyperplastic carcinoma and
      carcinoma cuniculatum are both low-grade, extremely well-differentiated SCC
      variants characterized by an indolent clinical course and good prognosis. The
      former, which may be confused with pseudoepitheliomatous hyperplasia,
      preferentially affects the inner foreskin mucosa of elderly men and the latter is
      a verruciform tumor with an endophytic, burrow-like pattern of growth.
      Pseudoglandular carcinoma (featuring solid tumor nests with extensive central
      acantholysis simulating glandular lumina) and clear cell carcinoma (human
      papillomavirus [HPV]-related tumors composed of periodic acid-Schiff positive
      clear cells) are aggressive tumors with a high incidence of inguinal nodal
      metastases. Papillary carcinomas are HPV-unrelated verruciform tumors composed of
      complex papillae with acanthosis, hyper- and parakeratosis, absence of
      koilocytes, irregular fibrovascular cores, and jagged tumor base. Finally, in
      warty-basaloid carcinomas areas of warty (condylomatous) and basaloid carcinomas
      coexist in the same tumor, either separated or intermingled, giving the tumor a
      variegated appearance. In this review special emphasis is given to the
      differential diagnosis of these special variants with a discussion of the
      possible implications for clinical management.

PMID- 22641955
TI  - The role of human papillomavirus infection in the pathogenesis of penile squamous
      cell carcinomas.
AB  - Emerging evidence suggests that penile cancer follows 2 etiologic pathways, 1
      related to human papillomavirus (HPV) infection and the other related to other
      factors including phimosis, chronic inflammation, and lichen sclerosus. HPV DNA
      is found in 47% to 48% of all penile tumors, and most of these cases correspond
      to high-risk genotypes, preferentially HPV-16. HPV status is associated with
      histologic subtype, with higher detection ratios in warty-basaloid carcinomas and
      lower detection ratios in keratinizing variants (ie, verrucous, papillary, and
      usual squamous cell carcinomas). It is the cell type, rather than a distinctive
      architecture, that is more strongly associated with HPV presence. The detection
      ratio is higher in tumors composed entirely or partially of cells with basaloid
      features. In addition, a few studies have evaluated the impact of HPV infection
      on the prognosis of patients with penile cancer. However, results are
      controversial, and more data are needed to clarify this matter. A proper
      understanding of the role of HPV in penile carcinogenesis might help in planning
      intervention strategies such as vaccination against HPV infection.

PMID- 22641956
TI  - Diagnostic problems in precancerous lesions and invasive carcinomas of the penis.
AB  - Penile precancerous and invasive lesions exhibit a variegated morphology.
      Although the diagnosis and classification of penile tumors is straightforward in
      most cases, a few entities are problematic, especially to pathologists from
      countries in which penile cancer is rarely encountered. The differential
      diagnosis of squamous hyperplasias from differentiated penile intraepithelial
      neoplasia or from extremely low-grade invasive neoplasms (eg, pseudohyperplastic
      and verrucous carcinomas) may be particularly difficult. Similarly, given the
      morphologic features shared by all verruciform tumors (ie, verrucous, warty,
      papillary, and cuniculatum carcinomas, along with giant condylomas), it is
      challenging at times to distinguish one from another. At the other end of the
      spectrum, because of their lack of differentiation, it is sometimes difficult to
      classify high-grade carcinomas, such as basaloid and sarcomatoid, which may have
      etiologic/prognostic implications. Penile mixed tumors, harboring more than 1
      histologic subtype and grade, constitute a frequent finding in routine pathology.
      The recognition of distinctive morphologic patterns and histologic grades in
      these tumors is important because these features could be related to etiologic
      factors, such as human papillomavirus infection, or they could influence outcome.
      Penile tumors with glandular features (eg, adenosquamous and mucoepidermoid
      carcinomas), although rare, may be confused with the more common pseudoglandular
      (adenoid, acantholytic) variant of squamous cell carcinomas, their main mimicker.
      In this review we provide clues that may help in the differential diagnosis of
      these lesions.

PMID- 22641957
TI  - Stratification systems as prognostic tools for defining risk of lymph node
      metastasis in penile squamous cell carcinomas.
AB  - Inguinal lymph node metastasis is the single most important factor for predicting
      survival in patients with penile squamous cell carcinomas. To estimate the
      likelihood of this event, investigators have combined pathologic features of the
      primary tumor in the form of stratification systems. In this article we review 3
      such systems (Solsona et al, J Urol 2001;165:1506; Hungerhuber et al, Urology
      68:621, 2006; and Chaux et al, Am J Surg Pathol 2009;33:1049) built upon
      histologic grade, extent and depth of tumor invasion, and perineural invasion. We
      evaluate their usefulness, limitations, and possible implications for the
      management of patients with penile cancer. We also provide clues for the proper
      identification and interpretation of these pathologic features. Inguinal
      metastases were observed in 64% to 83% of patients in high-risk groups, 20% to
      33% of intermediate groups, and 0% to 8% of low-risk groups. The results of these
      studies suggest that patients in high-risk groups could benefit from prophylactic
      bilateral groin dissection. In addition, patients in low-risk groups might be
      managed by surveillance alone. Finally, the authors suggest that additional
      approaches, such as sentinel lymph node biopsy, should be used for the
      intermediate-risk group. The identification of other pathologic features, such as
      vascular and perineural invasion, could tip the scales in problematic or
      paradoxical cases. The fate of these risk groups would be better defined by the
      identification of molecular biomarkers and genetic profiling.

PMID- 22641958
TI  - Sentinel lymph node biopsy in penile carcinoma.
AB  - Sentinel lymph node (SLN) biopsy is a fairly new technique that is becoming the
      standard of care for regional lymph node staging of many solid tumors. This
      technique is based on the hypothesis of stepwise distribution of malignant cells
      in the lymphatic system. The absence of tumor cells in the first lymph node(s) in
      the lymphatic drainage of a tumor would indicate the absence of further spread in
      the regional lymph node basin(s). Therefore, this first lymph node is the
      guardian (sentinel) of the regional lymph node basin. To localize the sentinel
      node preoperatively, lymphoscintigraphy is usually performed after intradermal
      peritumoral injections of colloid particles labeled with technetium-99m. The
      tracer is transported through the lymphatic channels to the first draining nodes
      in the groins and is visible on the lymphoscintigram as hot spots. The main
      advantage of SLN biopsy in penile cancer is to decrease the treatment-related
      morbidity without compromising the survival benefit for the patient. Recent
      figures indicate a false-negative rate of 7%, with a complication rate of less
      than 5% for SLN biopsy. In conclusion, sentinel node biopsy of patients with
      penile cancer has evolved into a highly reliable procedure enabling the detection
      of lymph node invasion at the earliest possible time with minimal morbidity. With
      this technology at hand, which minimizes the treatment-related morbidity, there
      is hardly any place for standard lymphadenectomy in penile cancer patients.

PMID- 22641959
TI  - Histologic classification of penile intraepithelial neoplasia.
AB  - Penile squamous cell carcinomas (SCCs) and their corresponding precancerous
      lesions can be classified in 2 major groups: human papillomavirus (HPV) related
      and HPV unrelated. In the former (warty and basaloid SCC), there is a
      predominance of undifferentiated basaloid cells. In the latter (eg, usual,
      papillary, and verrucous SCC), the predominant cell is larger with abundant
      eosinophilic cytoplasm. Based on these morphologic features, a new term, "penile
      intraepithelial neoplasia" (PeIN), was proposed. PeIN was further subclassified
      into differentiated and undifferentiated, with the latter being subdivided into
      basaloid, warty, and warty-basaloid subtypes. Macroscopically, PeIN subtypes are
      indistinguishable. Microscopically, differentiated PeIN is characterized by
      acanthosis, parakeratosis, enlarged keratinocytes with abundant "pink" cytoplasm
      (abnormal maturation), and hyperchromatic cells in the basal layer. In basaloid
      PeIN the epithelium is replaced by a monotonous population of uniform, small,
      round, and basophilic cells. Warty PeIN is characterized by a spiky surface,
      prominent atypical parakeratosis, and pleomorphic koilocytosis. Warty-basaloid
      PeIN show features of both warty and basaloid PeIN. There is a significant
      association of subtypes of PeIN with specific variants of invasive SCCs. This is
      a simple and reproducible nomenclature for penile precancerous lesions based on
      cell type and differentiation. It takes into account the similarities between
      vulvar and penile pathology and the hypothesis of a bimodal pathway of penile
      cancer progression.

PMID- 22641960
TI  - The process addictions and the new ASAM definition of addiction.
AB  - Addiction is a primary, chronic disease involving brain reward, motivation,
      memory and related circuitry; it can lead to relapse, progressive development,
      and the potential for fatality if not treated. While pathological use of alcohol
      and, more recently, psychoactive substances have been accepted as addictive
      diseases, developing brain science has set the stage for inclusion of the process
      addictions, including food, sex, shopping and gambling problems, in a broader
      definition of addiction as set forth by the American Society of Addiction
      Medicine in 2011.

PMID- 22641961
TI  - Behavioral addictions: an overview.
AB  - The legitimacy of nonsubstance addictions has received increased attention from
      clinicians, researchers and the general population as more and more individuals
      report symptoms consistent with impairment of impulse control. The clinical
      presentation of these disorders is varied, as compulsive activities may include:
      gambling, eating, sex, shopping, use of the Internet or videogames or even
      exercising, working or falling in love. As such, there is great controversy in
      diagnosing, treating or even naming these conditions, as many of these behaviors
      are daily rituals instrumental to our ultimate survival. Historically, the phrase
      "impulse control disorders" described these conditions but many researchers and
      clinicians also use the term "behavioral addictions," "process addictions" or
      "impulsive-compulsive behaviors" to report behavioral pathology. This review
      summarizes the data of each of these behavioral addictions from epidemiology to
      neurobiology to treatment options. Research suggests similarities between natural
      and drug reward processing but clinical evidence supports the utilization of
      treatment modalities for these behavioral conditions that can sometimes differ
      from traditional drug treatment.

PMID- 22641962
TI  - The clinical utility of brain SPECT imaging in process addictions.
AB  - Brain SPECT imaging is a nuclear medicine study that uses isotopes bound to
      neurospecific pharmaceuticals to evaluate regional cerebral blood flow (rCBF) and
      indirectly metabolic activity. With current available technology and knowledge
      SPECT has the potential to add important clinical information to benefit patient
      care in many different areas of a substance abuse practice, including in the area
      of process addictions. This article explores the ways brain SPECT has the
      potential to be useful to clinicians in helping to understand and direct
      treatment for complex cases of obesity and sexual addictions. Areas where SPECT
      can add value include helping clinicians ask betterquestions, helping them in
      making more complete diagnoses, evaluating underlying brain systems pathology,
      decreasing stigma and increasing compliance, and visualizing effectiveness via
      follow-up evaluations. In particular, SPECT can help in identifying and assessing
      the issue of brain trauma and toxicity in process addictions, which may be
      significant contributing factors in treatment failure. Three illustrative case
      histories will be given.

PMID- 22641963
TI  - Pathological gambling: a general overview.
AB  - Throughout the course of history, gambling has been a popular activity across
      most cultures. In the United States, gambling has transitioned from early
      acceptance to prohibition to widespread proliferation. For most, gambling is a
      relaxing and recreational activity; however, for some individuals gambling
      becomes more than harmless fun. The most severe form of gambling, pathological
      gambling, is recognized as a mental health disorder. Pathological gambling is
      currently classified as an impulse control disorder in the DSM-IV-TR, but it
      shares many important features with substance use disorders, especially in terms
      of diagnostic criteria, clinical course, and treatment. Consequently, the DSM-V
      Task Force has suggested that pathological gambling be reclassified and included
      in a new category entitled "Addiction and Related Disorders." The category would
      include both substance-related and non-substance/behavioral addictions. This
      article provides a general overview of some of the available literature regarding
      pathological gambling and includes the presentation of a number of relevant
      topics including etiology, risk factors, comorbidity, prevention, and treatment.
      However, as with most complex, multifaceted, and multidimensional phenomena, more
      research is needed in order to improve both prevention and treatment efforts for
      pathological gambling.

PMID- 22641965
TI  - The obesity epidemic and food addiction: clinical similarities to drug
      dependence.
AB  - As of 2010 nearly 70% of adult Americans were overweight or obese. Specifically,
      35.7% of adult Americans are obese, and this is the highest level of obesity in
      the recorded history of the United States. A number of environmental factors,
      most notably the number of fast food outlets, have contributed to the obesity
      epidemic as well as to the binge prone dynamic. There is evidence that bingeing
      on sugar-dense, palatable foods increases extracellular dopamine in the striatum
      and thereby possesses addictive potential. Moreover, elevated blood glucose
      levels catalyze the absorption of tryptophan through the large neutral amino acid
      (LNAA) complex and its subsequent conversion into the mood-elevating chemical
      serotonin. There appear to be several biological and psychological similarities
      between food addiction and drug dependence including craving and loss of control.
      Nonetheless there is at least one apparent difference: acute tryptophan depletion
      does not appear to induce a relapse in recovering drug-dependent individuals,
      although it may induce dysphoria. In some individuals, palatable foods have
      palliative properties and can be viewed as a form of self medication. This
      article will examine environmental factors that have contributed to the obesity
      epidemic, and will compare the clinical similarities and differences of food
      addiction and drug dependence.

PMID- 22641966
TI  - The case for compulsive shopping as an addiction.
AB  - Addictive drugs like cocaine, opiates and nicotine, through direct or indirect
      means, hyperstimulate the dopamine (DA) reward system. Some behaviors, for some
      people, can have similar effects on the same DA reward circuitry resulting in
      very similar addictive behavior patterns and consequences. Although the term
      "addictive" has been used loosely with many behaviors, it may be an appropriate
      term to describe compulsive shopping. Increased accessibility, hyperstimulating
      marketing techniques, a loss of the protective delay between impulse and
      purchase, and overvaluing of the shopping process and objects purchased may all
      contribute to the potentially addictive nature of shopping.

PMID- 22641964
TI  - Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a
      function of reward gene polymorphisms.
AB  - The nucleus accumbens, a site within the ventral striatum, plays a prominent role
      in mediating the reinforcing effects of drugs of abuse, food, sex, and other
      addictions. Indeed, it is generally believed that this structure mandates
      motivated behaviors such as eating, drinking, and sexual activity, which are
      elicited by natural rewards and other strong incentive stimuli. This article
      focuses on sex addiction, but we hypothesize that there is a common underlying
      mechanism of action for the powerful effects that all addictions have on human
      motivation. That is, biological drives may have common molecular genetic
      antecedents, which if impaired, lead to aberrant behaviors. Based on abundant
      scientific support, we further hypothesize that dopaminergic genes, and possibly
      other candidate neurotransmitter-related gene polymorphisms, affect both hedonic
      and anhedonic behavioral outcomes. Genotyping studies already have linked gene
      polymorphic associations with alcohol and drug addictions and obesity, and we
      anticipate that future genotyping studies of sex addicts will provide evidence
      for polymorphic associations with specific clustering of sexual typologies based
      on clinical instrument assessments. We recommend that scientists and clinicians
      embark on research coupling the use of neuroimaging tools with dopaminergic
      agonistic agents to target specific gene polymorphisms systematically for
      normalizing hyper- or hypo-sexual behaviors.

PMID- 22641967
TI  - Prescribing practices and the prescription drug epidemic: physician intervention
      strategies.
AB  - Prescription drug abuse is increasingly recognized as the United States' fastest
      growing drug problem, rising dramatically since the early 2000s, and particularly
      affecting adolescents and young adults. Federal officials are urging legislation
      to educate physicians about the use and effects of potent narcotics, which are
      increasingly being prescribed for chronic pain. ASAM developed strategies in the
      1980s to identify the small minority of misprescribers and focused educational
      and retraining efforts on these individuals. As health reform and more prevalent
      pain management put more primary care physicians in a gatekeeper role to manage
      the medical care of addicts, these clinicians must become aware of the abuse
      potential of the powerful narcotics they prescribe. Increased reference to state
      maintained controlled medication databases can also reduce misprescribing.

PMID- 22641968
TI  - Six lessons from state physician health programs to promote long-term recovery.
AB  - The success of the nation's state physician health programs (PHPs) provides
      important new evidence on the potential for dramatically reducing relapse and
      promoting long-term recovery from substance use disorders. This article
      summarizes the findings of the first national PHP study and outlines six lessons
      learned from this model of care management: (1) zero tolerance for any use of
      alcohol and other drugs; (2) thorough evaluation and patient-focused care; (3)
      prolonged, frequent random testing for both alcohol and other drugs; (4)
      effective use of leverage; (5) defining and managing relapses; and (6) the goal
      of lifelong recovery rooted in the 12-Step fellowships. PHPs are a part of a new
      paradigm of care management that includes the programs developed for commercial
      pilots (HIMS) and for attorneys (CoLAP). Elements of this model of care have been
      used with a dramatically different patient population, and with similar success,
      in the criminal justice system in HOPE Probation and 24/7 Sobriety. The authors
      review these programs and discuss implications for extending elements of the new
      paradigm more widely.

PMID- 22641969
TI  - Searching for answers: proper prescribing of controlled prescription drugs.
AB  - Prescription drug abuse is increasing at alarming rates in this country. Most
      often drugs are obtained through relatives or friends. An important step in
      addressing this problem is educating healthcare providers in the proper
      prescribing of scheduled drugs. Physicians and other healthcare workers receive
      little training in proper screening for substance abuse, proper prescribing of
      scheduled drugs, and referral for those needing treatment. Continuing medical
      education is one venue for addressing this problem. However, screening, brief
      intervention and referral for treatment (SBIRT) should be taught in medical
      school and residency.

PMID- 22641970
TI  - Predictors of nonmedical use of prescription stimulants.
AB  - College students across the U.S. engage in nonmedical use of prescription
      stimulants (NMUPS) at increasing rates. While it has been found that use is
      frequently motivated by a belief that stimulants will act as a study aid, little
      is known about predictors of NMUPS. The present study addressed impulsivity,
      outcome expectancies, and evaluations of expected outcomes as predictors of NMUPS
      in a sample of 206 college students at a mid-Atlantic university. Approximately
      26.1% of students endorsed past year NMUPS. Results indicated an increased
      likelihood of self-reported NMUPS was associated with increases in lack of
      premeditation, sensation seeking, positive expectancies and positive evaluations.
      Moreover, the extent to which participants believed that potential negative
      consequences were more severe was associated with a decreased likelihood of
      NMUPS. The current study suggests that impulsive personality, outcome
      expectancies, and evaluations of expected outcomes are important predictors of
      NMUPS among college students. Future research should consider other potential
      predictors of NMUPS in order to inform the development of prevention strategies.

PMID- 22641971
TI  - The evolution of hypertension treatment in Belgium, a pharmacoepidemiological
      study.
AB  - OBJECTIVES: The aim of this paper is to study the number of patients treated for
      hypertension and the evolution in usage of different classes of antihypertensive
      medication. METHODS: Data from 1997 to 2009 was extracted from Pharmanet, a
      nation-wide database of prescriptions of reimbursed medication in Belgium.
      RESULTS: In 2009, 25% of women and 20% of men were prescribed at least one
      antihypertensive drug. Prescription rates rose with age but already 25% of the
      population aged between 41 and 60 years were treated. More than 50% of the
      Belgians above 60 years took antihypertensive medication. From 1997 to 2009, a
      rise in absolute prescription rate was observed for all antihypertensive drug
      classes. Diuretics and beta blockers remain by far the most frequently delivered
      drugs with stable prescription rates of 30% over this period. The largest rise is
      observed for angiotensin II receptor blockers (ARBs), which were only
      sporadically prescribed in 1997 and now account for 10.5% of the delivered
      antihypertensive drugs. A small rise is also noted for angiotensin-converting
      enzyme inhibitors (ACE-inhibitors) (12.3% in 1997 vs 15.6% in 2009). Their
      success comes at the expense of calcium antagonists, of which the delivered
      amount declined from 19.8% in 1997 tot 14.1% in 2009. A progressive rise in the
      prescription of fixed combination products is observed (from 15% in 1997 to 21%
      in 2009), and can probably be attributed to their growing availability but also
      to the recent guidelines, promoting their usage. CONCLUSION: Above age 60, the
      majority of the Belgians are treated with antihypertensive medication. There is a
      growing tendency for the use of renin angiotensin aldosterone system (RAAS)
      blockers and fixed combination products.

PMID- 22641973
TI  - Stroke prevention in atrial fibrillation: current status and emerging therapies.
AB  - Stroke is the most common cardiovascular disorder after heart disease, with a
      high mortality and often poor quality of life in survivors. Atrial fibrillation
      (AF), the most commonly occurring sustained cardiac arrhythmia increases the risk
      of stroke by five. However, stroke risk is not homogeneous and varies with
      associated morbidities and risk factors. Risk assessment scores have been
      developed and according to the calculated level of risk, guidelines recommend
      treatment with antithrombotic agents, preferably vitamin K antagonists (VKA).
      Despite these recommendations many patients with AF do not receive adequate
      thromboprophylaxis. The presence of AF is often not recognized and VKA are
      underused due to doctor- or patient-related factors and intrinsic disadvantages
      of these drugs. An awareness campaign for the diagnosis of AF is warranted,
      highlighting the risk of stroke. Novel anticoagulants that largely overcome many
      of the limitations of vitamin K antagonists are becoming available.

PMID- 22641972
TI  - Quality of life improvement after radiofrequency catheter ablation of outflow
      tract ventricular arrhythmias in patients with structurally normal heart.
AB  - INTRODUCTION: Patients with structurally normal hearts (SNH) suffering from
      ventricular tachycardia (VT) or frequent premature ventricular contractions
      (PVCs) are at low risk of sudden cardiac death. Any treatment ameliorates
      symptoms without a substantial influence on survival.The aim of this study was to
      prospectively evaluate the health-related quality of life (QoL) of patients with
      SNH undergoing elective radiofrequency ablation (RFA) of VT or PVCs. MATERIAL AND
      METHODS: Patients scheduled for RFA of VT or PVCs in SNH were enrolled. They
      underwent 24-h Holter ECG and QoL assessment (SF-36 questionnaire) at baseline
      and at 3-month follow-up. Results were compared within and between VT and PVCs
      groups. RESULTS: Among 44 enrolled patients:(i) 23 had VT; (ii) 21 had PVCs with
      a mean count of 18,711 +/- 10,378 beats/24h. Antiarrhythmic drugs (sotalol,
      propafenone) were more frequently used in the VT group than in the PVC group. All
      patients underwent successful RFA with no major complications with 2 cases of
      early reablation. At follow-up, a significant improvement 6 of 8 domains of SF-36
      was observed in the VT and PVCs groups respectively with no significant
      difference in physical and mental component summary score between both groups.
      CONCLUSIONS: Favourable outcome of radiofrequency ablation in terms of quality of
      life and safety supports the idea of aggressive treatment of ventricular
      arrhythmia in patients with structurally normal hearts who are symptomatic and/or
      prone to cardiomyopathy. Comparable improvement of QoL in patients with PVCs and
      VT is an additional argument for performing ablation in symptomatic patients with
      frequent ventricular contractions.

PMID- 22641974
TI  - Clinical findings associated with cardiovascular autonomic dysfunction in adult
      sickle cell anaemia patients.
AB  - BACKGROUND: Involvement of the cardiovascular autonomic nervous system in various
      diseases is often associated with increased morbidity and mortality. OBJECTIVE:
      The objective of this study was to examine the clinical features associated with
      cardiovascular autonomic neuropathy (CAN) in adult Nigerians with sickle cell
      anaemia. METHODS: A cross-sectional study was carried out on 62 steady state
      sickle cell anaemia patients recruited from the adult out-patient clinic.
      Cardiovascular autonomic dysfunction was determined based on abnormal values in
      at least two of five non-invasive tests: Valsalva manoeuvre, heart rate variation
      during deep breathing, heart rate response to standing, blood pressure response
      to sustained handgrip, and blood pressure response to standing. All the subjects
      were initially evaluated in the clinic for symptoms of cardiovascular disease and
      peripheral vascular disease, and then clinically examined to assess their
      cardiovascular and neurological status at rest. RESULTS: Out of the 44 patients
      with cardiovascular autonomic neuropathy 23 were males, while 21 were females.
      The mean ages were 28.3 +/- 5.8 y for patients with CAN and 28.0 +/- 5.0 y for
      patients without CAN (P = 0.817). Sickle cell anaemia patients with CAN had
      significantly lower ankle systolic blood pressure, reduced ankle brachial blood
      pressure index, mean arterial blood pressure and haematocrit than patients
      without CAN. Of all the variables evaluated leg ulcers, postural dizziness,
      erectile dysfunction in men, and history of recurrent acute chest syndromes were
      found significantly more in patients with CAN than without. Clinical
      abnormalities tend to worsen with increasing degree of cardiovascular autonomic
      dysfunction. CONCLUSION: Significant cardiac morbidity is associated with
      abnormal cardiovascular autonomic function in sickle cell anaemia.

PMID- 22641975
TI  - Mechanical ventilation with positive end-expiratory pressure in critically ill
      patients: comparison of CW-Doppler ultrasound cardiac output monitoring (USCOM)
      and thermodilution (PiCCO).
AB  - BACKGROUND: Aggressive mechanical ventilation can markedly and unpredictably
      affect cardiac function. The fall in cardiac output (CO) is due to a reduction in
      left ventricular stroke volume (SV). The aim of the present pilot study was to
      assess the effects of different positive end-expiratory pressure (PEEP) levels on
      circulatory function and to compare them with continuous wave (CW)-Doppler
      ultrasound cardiac output monitoring (USCOM) and a thermodilution-based
      haemodynamic monitoring system (PiCCO). METHODS: Twenty mechanically ventilated
      (PEEP < or = 10 mbar) adult patients (female n = 6, male n = 14, mean age 62
      years, mean SAPS II-score 48.5), the majority with pneumonia and septic shock)
      were followed with USCOM and PiCCO at stepwise increased PEEP-levels from 0-10
      mbar (1 mbar steps). The changes in CO/SV were recorded. RESULTS: With both
      methods, an increase of PEEP resulted in a decrease of SV and CO. Although the
      absolute decrease was consistently higher by USCOM, the changes of the parameters
      were qualitatively comparable. CO fell from 8.83 L/min (+/- 2.39) by 0.4 L/min to
      8.49 L/min (+/- 2.48) with PiCCO and from 9.3 L/min (+/- 3.43) by 1.0 L/min to
      8.3 L/min (+/- 3.2) with USCOM. The median CO/SV fell by 4.5%/5.2% with PiCCO and
      10.8%/9% with USCOM, respectively. Correlation of CO values with the two methods
      by Bland-Altman yielded comparable results (mean percentage error at PEEP 0 mbar
      13%, PEEP 10 mbar 18%). An adequate flow signal with USCOM was achieved in all
      patients. CONCLUSIONS: A significant influence of mechanical ventilation with
      PEEP on haemodynamic parameters was evident both with USCOM and PiCCO. While
      thermodilution methods like PiCCO are well established but time-consuming and
      invasive, CW-Doppler based USCOM constitutes an important tool for easy, rapid
      and reliable diagnosis and haemodynamic monitoring of critically ill patients.

PMID- 22641976
TI  - In patients with hypertrophic cardiomyopathy myocardial fibrosis is associated
      with both left ventricular and left atrial dysfunction.
AB  - AIMS: The aim of this study was to assess LA function by two-dimensional speckle
      tracking echocardiography and its relation with myocardial fibrosis in
      hypertrophic cardiomyopathy (HCM). METHODS: We enrolled 30 consecutive HCM
      patients in our study (20 males; age: 49.7 +/- 10.4 years, NYHA-class: 1.9 +/-
      0.7). Echocardiography was performed with assessment of global longitudinal LV
      strain (epsilon) and LA epsilon and strain-rate parameters (systolic, early
      diastolic, and late diastolic during atrial contraction). Each patient received
      delayed-enhancement magnetic resonance imaging (DE-MRI) to check for myocardial
      fibrosis. We divided the patients into two groups. Patients of group 1 had no
      fibrosis, group 2 demonstrated moderate or severe fibrosis in > or = 2 segments
      using a 17 segment-model of the LV. RESULTS: Moderate and severe fibrosis was
      observed in 20 patients (group 2: 66.7%). Global longitudinal LV epsilon (-13.0
      +/- 2.4 vs -20.6 +/- 3.2%, P < 0.001) and peak LA epsilon (-0.2 +/- 3.9 vs 17.9
      +/- 6.7%, P < 0.001) were reduced in group 2 in comparison with patients without
      myocardial fibrosis. In all patients peak LA epsilon correlated with global
      longitudinal LV epsilon (r = -0.78, P < 0.001). Patients with considerable
      myocardial fibrosis (group 2) had a higher indexed left atrial volume (35.7 +/-
      12.8 ml/m2 vs 24.1 +/- 8.6 ml/m2, P = 0.016). New York Heart Association class
      (NYHA) was higher in patients with severe myocardial fibrosis (2.2 +/- 0.7 vs 1.3
      +/- 0.5) and correlated with peak LA (r = -0.5, P = 0.008) and global LV epsilon
      (r = 0.5, P = 0.005). CONCLUSIONS: Occurrence of myocardial fibrosis in
      hypertrophic cardiomyopathy is associated with left atrial and ventricular
      dysfunction as well as with the severity of heart failure symptoms.

PMID- 22641977
TI  - Relation of the metabolic syndrome with proarrhythmogenic electrocardiographic
      parameters in patients without overt diabetes.
AB  - OBJECTIVES: We aimed to observe the relationship of the metabolic syndrome and
      proarrythmogenic ECG parameters and to evaluate a possible correlation of these
      parameters to the metabolic syndrome score in patients without overt diabetes
      mellitus. METHODS: The study population consisted of 142 patients with the
      metabolic syndrome and 170 age- and gender-matched control subjects. In the ECG
      recordings, resting heart rate, QRS duration, corrected QT duration and corrected
      QT dispersion were measured. Patients were classified into three groups based on
      number of fulfilled metabolic syndrome criteria: group 1 (three metabolic
      syndrome criteria), group 2 (four metabolic syndrome criteria) and group 3 (five
      metabolic syndrome criteria). RESULTS: Patients with the metabolic syndrome had a
      higher increased resting heart rate, QTcd, prolonged QRS and QTc duration.
      Resting heart rate increases significantly parallel to the increase in the
      metabolic syndrome score across the groups, whilst QRS duration remained
      unchanged. QTc duration and QTc dispersion were significantly higher in groups 2
      and 3 when compared to group 1. However, no significant differences were observed
      between groups 2 and 3. CONCLUSION: We demonstrated that the metabolic syndrome
      and its score related with increased resting heart rate and prolonged
      repolarization durations in patiens without overt diabetes mellitus. These pro
      arrhythmogenic parameters could be used in the development of risk stratification
      schemes for sudden cardiac death in patients with the metabolic syndrome.

PMID- 22641978
TI  - Beneficial role of spironolactone, telmisartan and their combination on
      isoproterenol-induced cardiac hypertrophy.
AB  - INTRODUCTION: Although spironolactone and telmisartan are reported to reduce the
      risk of morbidity and death, direct studies on their effects on isoproterenol
      induced cardiac hypertrophy are scanty. Hence the present investigation was
      carried out to study the effect of spironolactone, telmisartan and their
      combination on isoproterenol-induced cardiac hypertrophy. METHODS: Isoproterenol
      was administered intra-peritoneally in a dose of 5 mg/kg once daily for 10 days
      to Wistar rats. Spironolactone (20 mg/kg/ day) (SL), telmisartan (5 mg/kg/day)
      (TM) or their combination (SLTM) was administered for 10 days after which various
      biochemical and cardiac parameters were measured. RESULTS: Isoproterenol produced
      dyslipidaemia, hypertension, elevated cardiac enzyme and C-reactive protein
      levels (CRP), worsened haemodynamic parameters and produced cardiac hypertrophy,
      left ventricular (LV) hypertrophy and oxidative stress. Chronic treatment with
      SL,TM or SLTM significantly controlled dyslipidaemia and produced a significant
      reduction in the elevated creatine-kinase (CK) and CRP levels. TM or SLTM
      produced a decrease in elevated lactate de-hydrogenase levels; however, SL failed
      to produce this effect. Hypotension, tachycardia, and decreased rate of pressure
      development and decay were prevented by SL, TM and SLTM treatment. Chronic
      treatment with SL, TM or SLTM also produced significant reduction in LV collagen
      levels, cardiac and LV hypertrophy index and prevented oxidative stress.
      CONCLUSIONS: Our data suggests that SL, TM and SLTM produced a beneficial effect
      on cardiac hypertrophy.

PMID- 22641979
TI  - The occurrence of atrial fibrillation in former top-level handball players above
      the age of 50.
AB  - OBJECTIVE: Cardiac adaptation to sports activity in endurance athletes is
      considerably different from that in power athletes. The effects of a high-level
      team sport like handball, one of the most popular sports in the world, performed
      at a younger age, on cardiac rhythm in individuals above the age of 50 have not
      been investigated to date. METHODS: Thirty-three former top-level handball
      players from the first German league (6 former world champions and numerous
      Olympians) (57.5 +/- 5.5 y) joined our screening programme for former athletes
      and underwent electrocardiography, echocardiography and spiroergometry. Data were
      compared to 24 sedentary healthy controls. RESULTS: Ten of the 33 athletes
      suffered from atrial fibrillation (AF). Left ventricular diameter was 53.68 +/-
      4.88 mm in the athletes group and 50.58 +/- 4.12 mm in the healthy controls.
      Analysing the subgroups of handball players ('AF group' and 'non-AF group'),
      spiroergometry showed oxygen consumption at the anaerobic threshold of 27.54 +/-
      6.77 ml/kg/min in the AF group and 31.24 +/- 10.33 ml/kg/min in the non-AF group
      (P = 0.228). Absolute left atrial diameter was 44.34 +/- 4.41 mm in the AF group
      (non-AF group 38.94 +/- 3.77 mm, P < 0.001) (healthy controls 37.54 +/- 4.34 mm,
      compared with all athletes P = 0.015). In all individuals left ventricular wall
      thickness was within normal limits. However, myocardial walls were thicker in the
      AF group (11.28 +/- 1.83 mm) than in the non-AF group (9.44 +/- 1.26 mm, P =
      0.002). Athletes in the AF group (187.6 +/- 6.42 cm) were significantly taller
      than in the non-AF group (180.91 +/- 7.31 cm, P = 0.018). CONCLUSION: Not only
      endurance training, but also sports activity with a relevant static component,
      like team handball, might predispose for AF above the age of 50. LA size, height
      and myocardial wall thickness seem to affect the risk of developing AF. More data
      in non-endurance sports are mandatory to confirm this hypothesis.

PMID- 22641980
TI  - Extra- and intracellular recordings from the avjunction: discerning the
      mechanisms for irregular ventricular responses during supraventricular
      arrhythmias.
AB  - INTRODUCTION: There has been a long-standing controversy regarding the
      mechanism(s) to explain the irregular ventricular response during atrial
      tachycardia (AT) or atrial fibrillation (AF) and where the site of block, if any,
      resides in the atrioventricular (AV) junction. METHODS: We studied 12 Langendorff
      preparations perfused with modified Tyrode's solution containing 5-10 mM diacetyl
      monoxime which suppressed contractility but allowed the use of intracellular
      action potential (AP) recordings. Octapolar catheters (2-mm rings, 2-mm spacing)
      were secured along the tricuspid annulus from the apex to the base of the
      triangle of Koch and along the anterior limbus of the fossa ovalis to record
      extracellular, slow pathway, fast pathway, His bundle (Hb) and AV nodal (AVN)
      extracellular potentials as well as intracellular action potentials. RESULTS: AT
      or AF induced by rapid atrial pacing showed a variety of irregular responses due
      to: (1) Wenckebach conduction showing decrement within the AVN and progressive
      diminution of extracellular AVN potentials (n = 5); (2) repetitive concealed
      conduction proximal to the AVN (n = 3); (3) ectopic beats arising within the AVN
      (n = 2); (4) ectopic beats arising at the Hb (n = 2). CONCLUSIONS: In this
      experimental preparation, extracellular and intracellular recordings provided
      presumptive evidence for the mechanisms causing the irregularities of the
      ventricular response such as repetitive concealed conduction, enhanced
      automaticity or electrotonically triggered activity. Also more definitive
      determinations of the site of block in the AV junction were also obtained.

PMID- 22641981
TI  - Success of delayed thrombolysis for metallic tricuspid valve thrombosis.
AB  - We discuss the case of a 55-year-old woman with a history of gastric ulcer,
      mechanical tricuspid and mitral valve replacement and a pacemaker for post
      operative total heart block. The patient underwent elective pacemaker
      replacement. She developed a large infra-umbilical rectal sheath haematoma during
      bridging therapy with low-molecular-weight heparins (LMWH), for which she was
      treated with angiographic embolisation of the epigastric artery. Subsequently, an
      intravenous unfractionated heparin (UFH) drip was started. Shortly thereafter,
      the patient developed severe upper gastrointestinal bleeding, caused by a gastric
      ulcer with a visible vessel. Anticoagulant therapy was interrupted. On the third
      day after cessation of the UFH drip, the patient developed thrombosis of the
      prosthetic tricuspid valve, confirmed by transthoracic echocardiography and
      cinefluoroscopy. Due to the risk of bleeding (from gastric ulcer and rectus
      sheath), both thrombolytic therapy and redo surgery were deemed to pose an
      unacceptable risk. We decided to treat the patient with intravenous heparin and
      postpone thrombolytic therapy until after healing of the gastric ulcer. At 5
      weeks after the bleeding event, alteplase was administered, with dissolution of
      the thrombus and restoration of valve disc motion. No embolic or bleeding
      complications occurred thereafter and six months after the event, the patient is
      in excellent general condition.

PMID- 22641982
TI  - Severe tricuspid regurgitation secondary to dislodgement of the atrial loop into
      the right ventricle: an unusual complication of pacemaker implantation in a young
      adult.
AB  - Transvenous pacemaker leads may impair tricuspid valve function. Severe tricuspid
      regurgitation due to leaflet adhesion to the pacemaker lead has not been reported
      in a young adult patient in the literature. Our patient underwent a transvenous
      pacemaker implantation for symptoms of bradycardia. An atrial loop was created in
      the right atrium for future growth. After 10 years of follow-up, the patient was
      seen with severe tricuspid regurgitation and enlarged right heart structures due
      to migration of the atrial loop of the pacemaker lead into the right ventricle
      and adhesion of the lead to the tricuspid valve. Cardiac surgery and epicardial
      pacing was the chosen procedure to solve this problem. The venous system and
      right heart valves should be carefully observed during the follow-up of children
      who underwent transvenous pacing.

PMID- 22641983
TI  - From a wide to a narrow QRS tachycardia and back. What is the mechanism?
AB  - A 40-year-old man developed a near syncope during exercise due to a wide complex
      tachycardia with periods of changing RR intervals accompanied by changes in QRS
      morphology. The differential diagnosis of this electrocardiographic pattern is
      discussed.

PMID- 22641984
TI  - Coronary artery ectasia due to microfistulae.
AB  - The pathogenesis of coronary artery ectasia (CAE) is not fully understood and
      associated with a vast group of disorders. We present a rare case of CAE of the
      left coronary artery associated with microfistulae. Microfistulae bypass
      myocardial capillaries and decrease the distal blood flow. The coronary artery
      responds to this coronary steal phenomenon with a compensatory dilatation,
      causing diffuse ectasia to catch up for the considerable decrease in coronary
      diastolic perfusion pressure. Although segmental dilatation is frequently seen in
      association with hypertension, one should think of microfistulae as an underlying
      cause of diffuse coronary ectasia.

PMID- 22641985
TI  - Carcinoid heart disease: typical findings on echocardiography and cardiac
      magnetic resonance.
AB  - Carcinoid syndrome is often complicated by carcinoid heart disease. Deposition of
      carcinoid plaques on the endocardium of the tricuspid and pulmonary valves causes
      the typical echocardiographic iconography with thickening of the leaflets and
      valvular insufficiency and/or stenosis leading to right heart failure.
      Additionally, the fibrous plaques can be visualized with cardiac magnetic
      resonance using delayed enhancement sequences. Accurate assessment of the
      dimensions of the dilated right ventricle by magnetic resonance implicates
      therapeutic options and defines prognosis. We report the case of a patient with
      advanced right heart failure as the clue to the diagnosis of carcinoid syndrome.
      Echocardiography was suggestive. Advanced investigation with magnetic resonance
      confirmed carcinoid plaque deposition on the tricuspid and the pulmonary valves,
      and we also had evidence of plaque deposition in the right ventricle.
      Multimodality imaging is essential in the investigation of this rare disorder.

PMID- 22641986
TI  - Haemochromatosis, sinus node dysfunction and Brugada syndrome--a menage a trois
      of findings in one and the same patient: coincidence or causality?
AB  - We describe the case of a 52-year-old male patient with a recently diagnosed
      hereditary haemochromatosis who was referred to our electrophysiology laboratory
      due to presyncopal spells during physical exertion. The electrophysiological
      study unexpectedly revealed a sinus node dysfunction as well as a Brugada
      syndrome--both diagnosed on the grounds of an ajmaline test.

PMID- 22641987
TI  - Elevated troponin T levels in a female carrier of Duchenne muscular dystrophy
      with normal coronary angiogram: a case report and review of the literature.
AB  - We present the case of a 48-year-old female carrier of Duchenne muscular
      dystrophy (DMD) with repeatedly documented levels of elevated troponin T without
      arguments for cardiac ischaemia. Elevated levels of troponin T are frequently
      reported in DMD patients and may function as a useful cardiac index to assess
      dystrophic degeneration of the myocardium in a subclinical stage. Cardiac
      troponins may help the clinician to diagnose myocardial damage in a very early
      stage of cardiac impairment independently from skeletal muscle degeneration.

PMID- 22641988
TI  - Cytomegalovirus myocarditis in an immunocompetent patient.
AB  - Viral infections can lead to myocardial inflammation, resulting in acute
      myocarditis. Acute myocarditis is mostly self-limiting, but it can lead to severe
      dilated cardiomyopathy and rarely to acute cardiac tamponade. We report a rare
      case of myocarditis in a young immunocompentent male patient due to a recent
      cytomegalovirus (CMV) infection. The clinical presentation was an influenza-like
      syndrome, classical for a CMV infection, in combination with mild chest pain.
      Further exploration showed inflammation-compatible perimyocardial images on
      magnetic resonance imaging (MRI). Following the symptomatic perimyocardial
      inflammation, the patient developed an acute asymptomatic self-limiting CMV
      hepatitis, a rare combination. Moreover, there was a remarkable evolution of both
      clinical signs with first increasing cardiac enzymes due to myocarditis and later
      on development of acute hepatitis. In this case report, we present the typical
      MRI images of myocarditis and discuss the CMV cardiac effects as well as the
      combination of CMV myocarditis and hepatitis.

PMID- 22641989
TI  - Q fever infection: inflammatory aortic root aneurysm in an HIV positive patient.
AB  - We describe a case of Q fever infection with an inflammated proximal ascending
      aortic aneurysm in an HIV-infected patient. The patient was treated with aortic
      root replacement and medication for Q fever, a combination of doxycycline and
      hydroxychloroquine in addition to highly active antiretroviral therapy. The
      combination of Q fever and HIV infection has rarely been documented. A case of Q
      fever infection of a proximal ascending aorta aneurysm in a patient with HIV co
      infection has never been described before.

PMID- 22641990
TI  - Relations between professional medical associations and the healthcare industry,
      concerning scientific communication and continuing medical education--a policy
      statement from the European Society of Cardiology.

PMID- 22641991
TI  - [Swelling of the middle finger: "pulled" by a horse].

PMID- 22641992
TI  - [Of dogs and humans: a huge meal].

PMID- 22641993
TI  - [Specialized ambulatory palliative care: is it available for the most severely
      ill?].

PMID- 22641994
TI  - [Responsibilities for the general practice team: who manages the internet?].

PMID- 22641995
TI  - [Spurned maternal love: "is my child autistic"?].

PMID- 22641996
TI  - [Can they explain recurrent fever? Reddish nodules of fingers and toes].

PMID- 22641997
TI  - [How vertigo in the elderly develops, and how it can be stopped: accidental falls
      risk!].

PMID- 22641998
TI  - [Expanded arsenal in atrial fibrillation: bye-bye marcumar?].

PMID- 22641999
TI  - [Naturopathy consultation. What helps with appetite loss?].

PMID- 22642000
TI  - [Cultural diversity in general practice: integration with understanding and humor
      (interview by Martin Bischoff)].

PMID- 22642001
TI  - [Osteoporosis contribution in CME special issue of MMW: these claims contradict
      the DVO guideline].

PMID- 22642002
TI  - [You have to take the prostate cancer seriously].

PMID- 22642003
TI  - [Early diagnosis of prostate cancer].

PMID- 22642004
TI  - [Management of prostate cancer].

PMID- 22642005
TI  - [Recurrent female urinary tract infection].

PMID- 22642006
TI  - [Recent advances in polymyalgia rheumatica].

PMID- 22642007
TI  - [Sleep disorders: successful combination: sleep health behavior and
      phytotherapy].

PMID- 22642008
TI  - [Valerian and hops complement each other well].

PMID- 22642009
TI  - [Post mortem examination. Signs of certain death].

PMID- 22642010
TI  - [Post mortem examination--cause of death].

PMID- 22642011
TI  - [German Hypertension Society: update on the management of hypertension].

PMID- 22642012
TI  - [Complicance, adherence, empowerment. More success in treatment of diabectic
      patients by improved cooperation].

PMID- 22642013
TI  - [Agitation and aggressive behavior in demented patients: pain therapy improves
      behavioral problems].

PMID- 22642015
TI  - [Blisters in the palm of the hand: was it the hedgehog?].

PMID- 22642014
TI  - [Depression: possible etiology: circadian dysregulation].

PMID- 22642016
TI  - [Prescribing fictitiously approved drugs: regress threatens!].

PMID- 22642017
TI  - [Empowered patients? "Dubious information" from the web complicate physician
      patient dialogue].

PMID- 22642018
TI  - [General practice value: group practices have greater value than individual
      practices].

PMID- 22642019
TI  - [Frequently asked questions on urinary tract infections: guideline adherent
      treatment].

PMID- 22642020
TI  - [Bite injuries frequently lead to wound infections: better to use antibiotics
      once too often!].

PMID- 22642021
TI  - [Naturopathy consultation. Liver diseases].

PMID- 22642022
TI  - [Chest constriction: what has gone astray in the thorax?].

PMID- 22642023
TI  - [COPD patients with heart failure: no concern about the beta blocker!].

PMID- 22642024
TI  - [Recurrent severe infections: is an immunologic deficiency possible? (interview
      by Dr. Christine Starostzik)].

PMID- 22642025
TI  - [Evidence for an immune defect: fact check with ELVIS].

PMID- 22642026
TI  - [Lip cyanosis in dapsone therapy: should the dosage be reduced?].

PMID- 22642027
TI  - [Young diabetic patient with high HbA1c: granting an automobile driving approval
      certification?].

PMID- 22642028
TI  - [Rapid postprandial blood glucose control: indications for better cardiovascular
      protection in the diabetic patient].

PMID- 22642029
TI  - [Deficiencies and barriers in pallative care].

PMID- 22642030
TI  - [Emergency in palliative care].

PMID- 22642031
TI  - [Multiprofessional teamwork is a main characteristic of palliative care].

PMID- 22642032
TI  - [Emergency checklist: head laceration].

PMID- 22642033
TI  - [Deep venous thrombosis].

PMID- 22642034
TI  - [Atypical course of pneumonia, a case report].

PMID- 22642035
TI  - [Resistant arterial hypertension].

PMID- 22642036
TI  - [Therapy and prevention of fracture pain in osteoporosis].

PMID- 22642038
TI  - [Drug utilization in older people will get better. Results based financial
      support is distributed to counties and municipalities].

PMID- 22642037
TI  - ["Overload of the emergency department" - a Swedish definition is needed].

PMID- 22642039
TI  - [Youth medicine tools support when dealing with young patients].

PMID- 22642040
TI  - [Death and morbidity among young people causes concern nationally and globally].

PMID- 22642041
TI  - [Helping young people to make tough decisions].

PMID- 22642042
TI  - [Biopsychosocial encounters good for young people with chronic conditions].

PMID- 22642043
TI  - [Young patients in hospitals are pinched into a corner].

PMID- 22642044
TI  - [Schools can create health].

PMID- 22642045
TI  - [All young people have a right to sexual health].

PMID- 22642046
TI  - [Frailty is a good concept for finding older people with a great need for care].

PMID- 22642047
TI  - [Aneurysm--drama and pathological aesthetics].

PMID- 22642048
TI  - [Self perceived burden from informal care: construction of the EDIZ-plus].
AB  - To measure the experienced burden by informal carers (N = 2.444), a 15-item
      Mokken scale has been developed. This concerns an extended version of the EDIZ
      ("Ervaren druk door Informele zorg"); several items refer to the pressure of time
      brought by the combination of labour and care and the consequences for the health
      of the informal carers are added to the EDIZ. We call this new scale the EDIZ
      plus; it concerns a reliable one-dimensional and hierarchical scale which extends
      from o (no burden) to maximum 15 (severe burden). First, the burden manifests
      itself in feelings of responsibility of the carer, followed by having difficulty
      with combining work and family tasks and ultimately exceeding all limits due to
      too many obligations. In most cases this last group does not only deal with
      conflicts at home or at work and a decline in their own health, they also
      experience all other problems in the scale. The presumed limit for overburdening
      is enclosed by the proposition 'caring put too much pressure on me'. This is a
      score on the EDIZ-plus of nine or higher. Furthermore, the scale has proved to be
      usable for several population groups, such as carers of partners and children,
      parents/parents-in-law and carers of different patient populations (people with
      dementia, mental disability or a chronic disease). The EDIZ-plus is not only
      suitable because of its reasonable psychometric qualities, but also because of
      the usability in different populations.

PMID- 22642049
TI  - [Accessible health information: a question of age?].
AB  - Aging and digitalisation are important trends which have their impact on
      information accessibility. Accessible information about products and services is
      of crucial importance to ensure that all citizens can participate fully as active
      members of society. Senior citizens who have difficulties using new media run the
      risk of exclusion in today's information society. Not all senior citizens,
      however, encounter problems with new media. Not by a long shot. There is much to
      be said for 'aged heterogeneity', the concept that individual differences
      increase as people age. In two explorative qualitative case studies related to
      accessible health information--an important issue for senior citizens--that were
      conducted in the Netherlands, variables such as gender, education level and
      frequency of internet use were therefore included in the research design. In this
      paper, the most important results of these case studies will be discussed.
      Attention will be also paid to complementary theories (socialisation, life
      stages) which could explain differences in information search behaviour when
      using old or new media.

PMID- 22642050
TI  - [Refusal of food and fluids of a psychiatric patient in order to hasten death:
      obstacles for patient, family and care-team].
AB  - In this case-report we present a patient with a psychiatric history of a chronic
      depressive disorder. After a period of several years of ambivalence, he decided
      to refuse nutrition and hydration because he--in the words of the Royal Dutch
      Medical Association--was "suffering from life". There was no request for
      euthanasia or physician assisted suicide. His first attempt, that lasted six
      weeks, did not result in his death. A second attempt, four months later, ended
      successfully. We describe the pitfalls that the patient, his family and the
      professional caregivers faced in both trajectories. The premorbid psychiatric
      disorder with polypharmacy and several psychotropic drugs as a result, the
      enormous complaints of thirst, the role of his wife and the dilemmas faced by the
      professionals made this case very complex. These issues make such cases very
      challenging for professional teams that have to provide good palliative care.

PMID- 22642051
TI  - [Alcohol in standard glasses disrupts the patient meeting].

PMID- 22642052
TI  - [Who can you trust?].

PMID- 22642053
TI  - [More focus on hyponatremia--a neglected clinical problem].

PMID- 22642054
TI  - [Survival in malignant gliomas has increased the last decade. Analysis of quality
      data].

PMID- 22642055
TI  - [Bacterial interactions may be a key to future antibiotics].

PMID- 22642056
TI  - [Guidelines for prehospital care in severe head injuries are not followed. Big
      difference between the Scandinavian guidelines and the regional Swedish
      guidelines].

PMID- 22642057
TI  - [Carotid blowout syndrome. Life-threatening condition in which endovascular
      treatment is the first choice].

PMID- 22642058
TI  - [Hyponatremia].

PMID- 22642059
TI  - [The venture will fundamentally change an ancient health-care system].

PMID- 22642060
TI  - [Hearing aid replaces audiological care].

PMID- 22642061
TI  - [Early bridge between preclinical and clinical research].

PMID- 22642062
TI  - [Skilled, sober "matrons" in the oldest female profession in the world].

PMID- 22642063
TI  - [Indoor dust as a pathway of human exposure to polybrominated diphenyl ethers
      (PBDEs)].
AB  - The brominated diphenyl ethers (PBDEs) belong to a class of synthetic, additive
      brominated flame retardants (BFRs). PBDEs are used to reduce the flammability of
      commercial and household products such as textiles, various plastic polymers,
      furnishing foam, and electronic equipment. People spend a large percentage of
      their life-time indoors at home, in offices and cars, etc, providing many
      opportunities for lengthy exposure to PBDEs from residential settings and
      commercial products in an indoor environment. In recent time, the foodstuffs,
      mainly food of animal origin, have been indicated as the main pathway of human
      exposure to PBDEs. However, many studies have shown that the indoor environment,
      mainly indoor dust, can be also a significant source of exposure to PBDEs,
      especially for younger children (toddlers) because of their behavioral patterns,
      eg. putting fingers, toys, and other items in their mouth. Numerous studies show
      that the median intakes of PBDEs via dust for adult range from 1.41 to 277 ng x
      day(-1) is lower than that via food which range from 135 to 333 ng x day-', while
      the median intake of these compounds via indoor dust for children range from 101
      to 404 ng x day(-1) is much higher than via food: 77-190 ng x day(-1). The
      congener pattern observed in the indoor dust is different to that found in food.
      The indoor dust is dominated by the congener BDE-209 vs. food where the most
      dominated congeners are BDE-47 and BDE-99. Human exposure to PBDEs and other
      brominated flame retardants (BFRs) is widely widespread throughout the world and
      it depends on a country range of usage, production and legislation concerning
      these chemicals as well as a citizen's behavior. Generally, human exposure has
      been found higher in North America than in Europe and Asia. Within European
      countries the significant highest concentrations in dust have been found in the
      United Kingdom. It should be noted that many uncertainty factors such as personal
      habits, dietary preferences, and time spent in various rooms, cars and outdoors
      could affect the exposure assessment. In some cases the occupational exposure is
      the most important source of PBDEs for adults, for example air crews, car sale
      employees and disposal/recycling of electronic waste workers.

PMID- 22642064
TI  - [Evaluation of biological and clinical potential of paleolithic diet].
AB  - Accumulating evidences suggest that foods that were regularly consumed during the
      human primates and evolution, in particular during the Paleolithic era (2.6-0.01
      x 10(6) years ago), may be optimal for the prevention and treatment of some
      chronic diseases. It has been postulated that fundamental changes in the diet and
      other lifestyle conditions that occurred after the Neolithic Revolution, and more
      recently with the beginning of the Industrial Revolution are too recent taking
      into account the evolutionary time scale for the human genome to have completely
      adjust. In contemporary Western populations at least 70% of daily energy intake
      is provided by foods that were rarely or never consumed by Paleolithic hunter
      gatherers, including grains, dairy products as well as refined sugars and highly
      processed fats. Additionally, compared with Western diets, Paleolithic diets,
      based on recently published estimates of macronutrient and fatty acid intakes
      from an East African Paleolithic diet, contained more proteins and long-chain
      polyunsaturated fatty acids, and less linoleic acid. Observational studies of
      hunter-gatherers and other non-western populations lend support to the notion
      that a Paleolithic type diet may reduce the risk of cardiovascular disease,
      metabolic syndrome, type 2 diabetes, cancer, acne vulgaris and myopia. Moreover,
      preliminary intervention studies using contemporary diet based on Paleolithic
      food groups (meat, fish, shellfish, fresh fruits and vegetables, roots, tubers,
      eggs, and nuts), revealed promising results including favorable changes in risk
      factors, such as weight, waist circumference, C-reactive protein, glycated
      haemoglobin (HbAlc), blood pressure, glucose tolerance, insulin secretion,
      insulin sensitivity and lipid profiles. Low calcium intake, which is often
      considered as a potential disadvantage of the Paleolithic diet model, should be
      weighed against the low content of phytates and the low content of sodium
      chloride, as well as the high amount of net base yielding vegetables and fruits.
      Increasing number of evidences supports the view that intake of high glycemic
      foods and insulinotropic dairy products is involved in the pathogenesis and
      progression of acne vulgaris in Western countries. In this context, diets that
      mimic the nutritional characteristics of diets found in hunter-gatherers and
      other non-western populations may have therapeutic value in treating acne
      vulgaris. Additionally, more studies is needed to determine the impact of
      gliadin, specific lectins and saponins on intestinal permeability and the
      pathogenesis of autoimmune diseases.

PMID- 22642065
TI  - [Induction of micronuclei in peripheral blood and bone marrow reticulocytes of
      male mice after subchronic exposure to x-rays and bisphenol A].
AB  - BACKGROUND: Ionizing radiation and xenoestrogens are widely present in the human
      environment. Bisphenol A (BPA) is used to manufacture polycarbonate plastics,
      epoxy and polyester resins. BPA is present in a great variety of products
      including: baby bottles, compact disks, thermal paper, safety helmets, bullet
      resistant laminate, plastic windows, car parts, adhesives, protective coatings,
      powder paints, polycarbonate bottles and containers, the sheathing of electrical
      and electronic parts, dental fillings. Food and beverage cans are protected from
      rusting and corrosion by the application of epoxy resins as inner coatings. Human
      activities involving the use of radiation and radioactive materials in industry,
      agriculture and research cause radiation exposure in addition to natural exposure
      coming from cosmic rays and naturally occurring radioactive substances.
      OBJECTIVE: The aim of the study was to estimate the effects of bisphenol A, X
      rays and combined exposure to X-rays and bisphenol A on the induction of
      micronuclei in the peripheral blood and in bone marrow reticulocytes of
      laboratory mice. MATERIAL AND METHOD: Pzh-Sfis male mice were exposed for 8
      weeks. Animals were treated with bisphenol A diluted in drinking water (5 mg/kg
      bw, 10 mg/kg bw, 20 mg/kg bw), irradiated 0.05 Gy of X-rays or exposed to a
      combination of both (0.05 Gy + 5 mg/kg bw BPA). The samples of peripheral blood
      were taken at 1, 4 and 8 week following the start of exposure, whereas the bone
      marrow after the end of experiment, only. The induction of micronuclei in
      reticulocytes were evaluated by using fluorescence microscope. RESULTS: Bisphenol
      A as well as ionizing radiation stimulated induction of micronuclei in peripheral
      blood and bone marrow reticulocytes. After the irradiation the level of
      micronuclei increased, whereas after exposure to BPA decreased related to time
      expired from beginning of experiment. Combined exposure of ionizing radiation and
      bisphenol A induced significantly higher frequency of micronuclei compared to the
      effect produced by BPA alone. The frequency of micronuclei in peripheral blood
      reticulocytes increased during the experiment. In all groups, the significantly
      lower induction ofmicronuclei in reticulocytes of bone marrow than of peripheral
      blood were observed. The levels ofmicronuclei in mice exposed to a combination of
      X-rays and BPA or to irradiation alone were slightly higher compared to those
      administered to BPA alone. CONCLUSIONS: Bisphenol A induced micronuclei in
      peripheral blood and bone marrow reticulocytes. Subchronic BPA exposure leads to
      diminished sensitivity of genetic material of reticulocytes on the induction of
      damage. X-rays is probably the agent which decided about DNA damage following
      combined exposure.

PMID- 22642066
TI  - Evaluation of soluble oxalates content in infusions of different kinds of tea and
      coffee available on the Polish market.
AB  - BACKGROUND: Tea and coffee are the potentially rich source of oxalic acid, which
      can act as a antinutrient. OBJECTIVE: The aim of this study was to determine and
      evaluate the content of soluble oxalates in teas and coffees available on the
      Polish market. MATERIAL AND METHOD: The green, red and black teas, and black
      natural ground and instant coffees were used for preparing the infusions. The
      manganometric method was used for the determination of the oxalates in the
      infusions. RESULTS: The mean oxalates content in the infusions from 3 g of black
      teas was 115.68 mg/100 cm3 and was higher as compared to red teas (101.91 mg/100
      cm3) and green teas (87.64 mg/100 cm3). Disregarding the variety of analyzed
      teas, the largest oxalates content was in infusions of pure one-component tea-
      "Sir Roger" (164.82-174.22 mg/100 cm3), while the lowest oxalates content was
      noted in the tea containing the components from other plants ("Bio-Active" with
      grapefruit juice--reaching as low level as 39.00 mg/100 cm3). Instant coffees
      contained larger amount of oxalates than natural ground coffees. Irrespective of
      the kind of the tested coffees, the lowest oxalates content was found in the
      infusions from the following coffees: Tchibo Exclusive--19.62 mg/100 cm3, Gala
      ulubiona--37.32 mg/100 cm3, and Maxwell House--38.40 mg/100 cm3, while the
      highest oxalates content in instant coffee--Nescafe Espiro 51.80 mg/100 cm3.
      CONCLUSIONS: The results revealed a significant relation between phytochemical
      composition of analyzed teas and coffees and the level of soluble oxalates in
      infusions prepared from the tested products.

PMID- 22642067
TI  - [Polychlorinated biphenyls in fractions of wheat grains and in selected bakery
      products].
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) form a group of synthetic aromatic
      chemical compounds, commonly occurring in the environment as a result of
      industrialisation. Despite the ban on PCBs production, their wide application in
      the past resulted in their common occurrence in all elements of the environment.
      The lipophilic nature of the compounds resulting in their accumulation in live
      organisms and in the human body may trigger many harmful effects. OBJECTIVE: The
      aim of this study was to determine the PCBs content in the selected species of
      wheat and in bakery products. The studies aiming at confirming possible
      correlation between the size of the grain of the selected species of wheat and
      the content of polychlorinated biphenyls were presented in this paper. Moreover,
      PCBs concentration in cereals' grains and in bread was compared. MATERIAL AND
      METHOD: The PCBs content was defined in different sizes of grains species of
      wheat i.e. Opatka, Zyta, Elena and Almari. The study included also two kinds of
      wheat bread. PCBs were determined after the extraction with n-hexane followed by
      sulphuric acid hydrolysis. Gas chromatography analysis was conducted on a PU 4600
      Unicam apparatus with an electron capture detector. RESULTS: The large variations
      in PCBs content depending on the grain size were confirmed. In the Opatka species
      the increase in the content of all determined congeners and the size of grain was
      confirmed. The lowest PCBs concentrations were in smallest grains (0,0090 mg/kg
      of fat), and the highest in the largest grains (0,0264 mg/kg of fat). In Zyta
      species PCBs content was also lowest in the smallest grains, however these
      results were not statistically significant. In the Elena species the increase in
      the PCBs content together with the increase in the grain size was confirmed.
      Basing on the determination coefficient it was found that the concentration of
      PCBs depends on the size of grains in 24%. The highest concentration of PCBs
      (0,0366 mg/kg of fat) was found in the largest grains, however differences
      between the examined fractions were not statistically significant. Similar
      tendencies were observed in Almari species. PCBs content in wheat bread was on
      lower level than in all of the examined species. CONCLUSIONS: It was confirmed
      that fraction 2,8 x 25 mm of all species of wheat grain had the highest PCBs
      content. The tendency to decrease of PCBs content with the decrease of the grain
      in size was observed. The relation between qualitative class of species and PCBs
      content was not confirmed. There were statistically significant differences in
      the PCBs concentrations between the wheat species within one size fraction. The
      results of PCBs content in wheat bread were lower than in all examined species of
      wheat. One can assume that for the production of bread collected for the study,
      the wheat originating from areas with low PCBs contamination was used. Somewhat
      higher PCBs content was observed in the wheat bread with bran added, probably due
      to higher PCBs accumulation in the bran, which contain higher fat and contribute
      therefore to the overall PCBs in the bran containing bread.

PMID- 22642068
TI  - [The evaluation of anti-nutritive components in beer on the example of oxalic
      acid].
AB  - BACKGROUND: Food in its composition contains anti-nutritional substances that
      reduces or prevents the use of valuable nutrients. The oxalic acid, as phytate
      and dietary fiber, occurs naturally in foods of plant origin, to which the beer
      is classified. The negative effect of oxalic acid is reducing the bioavailability
      of calcium and magnesium, and disorder of metabolism of the body's absorption of
      these elements from the diet. The excess of oxalic acid and its salt in the diet
      contributes to the formation of certain diseases, such as oxalate urolithiasis,
      osteoporosis, arthritis, etc. Due to the diuretic effect of beer, drinking
      moderate amounts of it is recommended as a preventive and support urinary tract
      disorders. OBJECTIVE: The aim of this study was to determine and comparison the
      oxalic acid content in selected beers available on the Polish market. MATERIAL
      AND METHOD: Fifty seven samples of beer were used for this study. These samples
      were divided into three groups depending on the alcohol concentration declared by
      the producers (1st group--below 5.5% vol., 2nd group--from 5.5 to 6.5% vol., 3rd
      group--above 6.5% vol.). The beer samples were incubated in the ultrasonic bath
      for 15 minutes following pH adjustments up to pH = 2 with the 1 mol/L
      hydrochloric acid to transform calcium oxalates into soluble form, then filtered.
      The oxalic acid concentration was measured by high performance liquid
      chromatography (HPLC) with conductivity detection. RESULTS: The concentration of
      oxalic acid in tested samples of beer ranged from 1.8 to 30.3 mg/L. No
      considerable differences between the concentration of oxalic acid in the three
      tested group of beer with the various content of the alcohol were found. Basing
      on the average concentrations of the oxalic acid in the different groups of the
      tested beers the positive trend in oxalic acid concentration related to the
      increase of alcohol could be observed. CONCLUSIONS: The very low concentration of
      oxalic acid allows to classify beer as food product safe for the human health in
      terms of low oxalates content.

PMID- 22642069
TI  - [Minerals intake from drinking water by young women].
AB  - OBJECTIVE: The aim of this study was to assess the intake of calcium, magnesium,
      iron, zinc, potassium and sodium with drinking water among 19-26 years old women,
      students at the Warsaw University of Life Sciences (SGGW). MATERIAL AND METHODS:
      Data on intake of drinking water and food products were collected based on 4-day
      record method. Information about kind of water usage to prepare beverages and
      meals were obtained by using a specific questionnaire. Minerals concentrations in
      water samples were assessed using the atomic spectrophotometer absorption (ASA)
      technique. RESULTS: The average consumption of drinking water equaled 870 +/- 389
      cm3/d (100-2738 cm3/d). The drinking water used by the women for meals or
      beverages preparation contributed in 9,8% of calcium and 3,8% of magnesium to
      their daily diet. Contribution of tap water in the intake of calcium and
      magnesium depended on the contents of these minerals in water, and amounted from
      6,0% (< or = 68,3 mg calcium on dm3 water--1st quartile) to 14,8% (> 112 mg/dm3-
      4th quartile) for calcium and from 2,9% (< or = 10,9 mg/dm3) to 4,7% (> 15,4
      mg/dm3) for magnesium. The contribution of iron, zinc, potassium and sodium was
      low, and not exceeded 2%. Comparing the average content of minerals in non-boiled
      and boiled tap water the cooking process influenced the levels of calcium (95,8
      +/- 31,8 vs 89,7 +/- 31,1 mg/dm3), magnesium (12,1 +/- 3,24 vs. 12,7 +/- 3,04
      mg/dm3), zinc (0,35 +/- 0,87 vs. 0,17 +/- 0,89 mg/dm3), potassium (3,31 +/- 2,67
      vs. 3,66 +/- 4,18 mg/dm3) and sodium (23,2 +/- 15,4 vs. 25,9 +/- 17,2 mg/dm3).
      Nevertheless, from the nutritional point of view the differences in the
      concentrations of these minerals were insignificant. Conclusions. Drinking water
      can be an important source of calcium and magnesium in diet, wherein the amount
      of the supplied element depends on its content in drinking water used for
      preparing beverages and/or meals.

PMID- 22642070
TI  - [Evaluation of fat sources consumption among the students of the Rzeszow
      University].
AB  - BACKGROUND: One of the most important parts of human diet is the appropriate
      quantity and quality of consumed fats. OBJECTIVE: The aim of this study was to
      assess the consumption of fat by students of the Rzeszow University. The
      evaluation was performed basing on the consumption frequency of food products
      consisting the major source of fat in the diet. MATERIAL AND METHOD: The
      evaluation was made on the basis of research on the frequency of consumption of
      selected food products which are the main source of fat in the diet. In the study
      there was used Blocke's survey form. 87 students including 72,4% woman and 27,6%
      man voluntarily participated in this study. RESULTS: The estimated overall
      assessment showed that the fat consumption by the majority of students was
      correct (women--74,6%, men--62,5%). However, it was found that approximately 15%
      of respondents consume too much fat. More frequent consumption of fat products
      was found in the male population of respondents. Reverse tendencies, consisting
      in reducing the consumption of products with a higher fat content can be
      indicated in the part of female students. The anomalies observed include
      excessive consumption by a part of respondents of fatty cured meats, luncheon
      meat or bacon, eggs and also doughnuts, cakes and cookies, as well as
      insufficient consumption of milk. CONCLUSION: Taking into consideration the role
      of fats for the body, they should be supplied in sufficient quantities, as
      irregularities in this regard may have a negative impact on the human health.

PMID- 22642071
TI  - [Factors influenced vitamin or mineral supplements use in a chosen group of
      children aged 6-12].
AB  - BACKGROUND: Due to growing popularity of food supplements the producers of such
      products introduce food supplements developed especially for children. This, as a
      consequence, may lead to a risk of exceeded intake of some nutrients. OBJECTIVE:
      The aim of this study was to identify determinants of vitamin/mineral supplements
      intake in 6-12-year-old children. METHOD: The study was conducted by
      questionnaire method among parents of 743 children attending primary schools.
      Dietary supplements during the year preceding the survey received 40% of
      children, while 16.7% on the tested day. RESULTS: It was found that women with
      secondary and higher education level more frequently reported use of such
      preparations by their children (43% and 40% respectively). Supplements received
      more children with moderate or slight deficient body weight (54.2%) compared to
      children with severe deficiency (29.7%) or obese (25.8%); children with chronic
      diseases (56%) compared to healthy (37%), participating in extracurricular sport
      activities (49%) compared to non-participating (35%) and children with more
      correct dietary habits. Simultaneously supplements and fortified products were
      used by 34% of children. CONCLUSIONS: . The decision of supplements use parents
      often undertook alone (67% of preparation), while only 31% of them after medical
      consultation. There is a need to educate children and their parents about the use
      of supplements and the risks associated with it.

PMID- 22642072
TI  - [Evaluation of the needs and possibilities of increasing the vitamin B12 content
      in diet].
AB  - BACKGROUND: Vitamin B12 belongs to the biologically active compounds related to
      cyanocobalamin group. The bioavailability of B12 from different food products
      varies considerably, for example from the chicken meat it ranges from 61 to 66%,
      from fish meat is 42%, and from eggs below 9% only. The deficiency of vitamin B12
      could easily be overcame by the appropriate diet or food supplements. OBJECTIVE:
      The aim of this study was to characterize the fortified with vitamin B12 food
      products available on the market and to assess the possibilities of increasing
      the intake of this vitamin by including such products into the daily diet.
      MATERIAL AND METHOD: The study was carried out in winter 2011, at eleven Warsaw
      supermarkets. Information about food products was based on label declarations.
      There were 220 products fortified with vitamin B12 from various food categories,
      like breakfast cereals, fruit juice, non-alcoholic beverages, cereals bars,
      candies, instant cocoa and tea, margarine, as well as soya products. Breakfast
      cereals (40%) and juice, non-alcoholic beverages (30%) were the largest groups.
      RESULTS. The highest amount of vitamin B12 was found in some candies (max. 4,5
      microg/100 g) and instant tea (max. 3,75 microg/100g). The lowest amount was
      found in some fruit beverages (min. 0,12 microg/100 g). There is possibility of
      increasing the vitamin B12 intake by consuming various fortified products: for
      instance a glass of soya drink (20,8% RDA), a cup of soya pudding (15%), a glass
      of instant tea (14%), apple juice (12,5%), a cereal bar (10%), a bowl of corn
      flakes (9,8%) or a slice of bread with margarine (7,5%). The intake of one
      average portion of chosen food products fortified with vitamin B12 provides about
      0,18-0,5 microg (7,5-20,8% Polish RDA for adults). CONCLUSIONS: The wide public
      education is essential for increasing the role of these products in nutrition, it
      is especially recommendable to vegetarian and elderly people.

PMID- 22642073
TI  - [Differences in dietary habits and food preferences of adults depending on the
      age].
AB  - BACKGROUND: Changes in the structure and functioning of the body occur with age.
      Also nutrition is continually modified. Eating habits may affect favorably or
      unfavorably on the process of aging and the functioning of various tissues,
      organs and the whole body. OBJECTIVES: The purpose of the study was to evaluate
      dietary habits and food preferences of patients in different age groups. In the
      studied groups also body mass index (BMI) and body fat content were analyzed.
      MATERIAL AND METHOD: 237 people (133 women and 104 men, age 18-79 years) were
      examined. The participants completed questionnaires of the frequency of food
      consumption and food preferences. The height, weight, body mass index (BMI), the
      percentage of body fat (BIA) were also measured. For statistical analysis the
      assessment of correlation Spearman's rank order and nonparametric ANOVA rank
      Kruskal-Wallis were used. RESULTS: With age, the frequency of milk (p < 0,05) and
      cheese (p < 0,05) consumption decreased whereas consumption of cottage cheese
      increased (p < 0,05). Increased consumption of offal (p < 0,05), salt (p < 0,05)
      and coffee (p< 0, 05) was also noted. With age, the respondents preferred animal
      fats (p < 0.05) and vegetable fats (p < 0.05). The frequency of butter
      consumption decreased (p < 0.05) and consumption of vegetable fats increased (p <
      0,05). The consumption of brown rice (p < 0,05), whole wheat pasta (p < 0,05) and
      cereals (p < 0,05) was reduced whereas the consumption of groats (p < 0,05)
      potatos (p < 0,05) and fruits (p < 0,05) increased. The decreased desire (p <
      0,05) and frequency of nuts / almonds consumption (p < 0,05) were noted. With
      age, the BMI and percentage of body fat were increasing (p < 0,05, R = 0,39, p <
      0,05, R = 0,31, respectively). CONCLUSIONS: Taste preferences and dietary habits
      vary depending on age and may be one of the elements affecting the increase in
      BMI, body fat content, bone mass loss and increased risk of metabolic disorders.
      The observed changes in dietary habits can contribute to the development of
      dyslipidemia, glucose dysmetabolism and arterial hypertension, especially in the
      presence of overweight and obesity.

PMID- 22642074
TI  - [Effects of dietary habits modifications on selected metabolic parameters during
      weight loss in obese persons].
AB  - BACKGROUND: Obesity is a serious social problem, one of the most important health
      issues of the modern world, especially in industrialized countries. Due to the
      prevalence obesity is a social disease, chronic and also a risk factor for many
      diseases such as hypertension, type 2 diabetes mellitus, coronary heart disease,
      gall stones or cancers. OBJECTIVE: The aim of the study was to examine and
      evaluation whether the systematic one-year modifications of dietary habits affect
      the changes in body weight and some metabolic parameters in obese patients.
      MATERIAL AND METHOD: 30 women and 30 men who declared intentions to decrease body
      weight were examined. The mean age of women was 48 +/- 12.5 years (range 31-72
      years), men 51 +/- 13.2 years (range 23-70 years). The questionnaire survey
      concerning the subject matter was designed in the Department of Dietetics and
      Clinical Nutrition, Medical University of Bialystok. At the initial and final
      visit the frequency of some products consumption were assessed and concentrations
      of some biochemical parameters in the peripheral blood were measured. RESULTS:
      Women after one-year dietotherapy significantly reduced the incidence of eating:
      pasta, fruit and vegetable juices, potatoes, ripening cheese, sugar, meat, bacon
      and lard, butter and cream, and increased incidence of eating dark bread, groats,
      rice, vegetables and fruit, cottage cheese, fish and vegetable oils. Men
      significantly reduced the incidence of eating: pasta, potatoes, ripening cheese,
      sweet beverages, bacon and lard, margarine, and increased the incidence of eating
      dark bread, groats, rice, vegetables, cottage cheese and fish. After one year the
      average body weight decrease was 2.8 +/- 7.1 kg in women and 1.4 +/- 3.2 kg in
      men. The average reduction in waist circumference was 3.6 +/- 6.5 cm in women and
      3.6 +/- 4,8 cm in men. HDL cholesterol levels increased significantly in women
      and not significantly in men. LDL cholesterol and triglyceride levels decreased
      significantly in both groups. In women systolic blood pressure decreased
      significantly by on average 9.7 mmHg, diastolic blood pressure by 9.2 mmHg, and
      in men by 10.9 mmHg and 8.2 mmHg respectively. CONCLUSIONS: Systematic
      nutritional education (every 3 months) may be the hope for effective body weight
      reduction and subsequent weight loss maintenance.

PMID- 22642075
TI  - [Selected nutritional habits children and teenagers aged 10-15 years].
AB  - OBJECTIVE: The aim of the study was the evaluation of chosen nutritional habits
      in group of children and teenagers attending elementary schools and junior high
      schools in Bialystok. MATERIAL AND METHODS: All together there were examined 1829
      children aged 10 to 15 (884 children from primary school and 945 students
      ofjunior high school). Body height and weight were measured to assess Body Mass
      Index. The results were interpreted with the use of the centile charts for the
      children recommended by The Institute of Mother and Child in Warsaw. Nutritional
      habits of children and teenagers were assessed based on the questionnaire form
      (designed in the Department of Dietetics and Clinical Nutrition, Medical
      University of Bialystok). The questionnaire contained questions regarding the
      number and type commonly consumed meals, the regularity of consumption, the
      frequency of additional eating between meals, and the frequency of consumption of
      selected groups of food products. RESULTS: In the study group of 1829 children
      the proper body weight was observed in more than 66% of the examined population.
      By analyzing the number of consumed meals it was stated that nearly half of all
      examined children consumed 4 meals a day. Among meals consumed most frequently
      were dinner, breakfast and supper. It was revealed that in comparison to boys
      girls of both younger and older group considerably more frequently included in
      their rations consumption of lunch. Eating between meals was rather common
      occurrence among all of the examined children. In all of compared groups low
      consumption of porridge, whole meal bread, milk, curd cheese, fishes, leguminous
      plants and raw fruits. At the same time it was shown that both older and younger
      boys considerably more often consumed meat and its preserves. Opposite tendency
      was noted in case of consumption of raw fruits. The majority of examined children
      and teenagers independently of gender groups declared excessive intake of sweets,
      which may have an unfavourable impact on their further development and health.
      CONCLUSIONS: Shown in this study a significant proportion of children with
      excessive body weight with persistently incorrect dietary intake requires
      targeted educational activities including prevention of diet related diseases,
      both in the school and home environment.

PMID- 22642076
TI  - [Evaluation of eating habits and nutritional behaviors of women in the
      perimenopausal period with the diagnosed celiac disease].
AB  - OBJECTIVE: The aim of this study was to evaluate eating habits and nutritional
      behaviors of women in the perimenopausal period with celiac disease diagnosed
      within the last 4 years. MATERIAL AND METHOD: The study covered a group of 26
      women, at the age of 51-54 years, with celiac disease diagnosed in the last 4
      years and staying on a gluten-free diet for 6 months to 4 years and agreed to
      participate in this studies. Information of nutrition were collected from the
      women, who, after an appropriate instruction, recorded the timing, type and
      amount of food consumed in the three days a week, selected at random. The amount
      of consumed portions was defined on the basis of the "Book of portions, products
      and dishes". The menus (78) were recorded in April and May. Collected data were
      prepared, based on a computer program Dietetyk 2009 Prof. RESULTS: The analysis
      of results achieved in this study enabled concluding that--from the viewpoint of
      the diagnosed disease--the nutritional patterns of the women were very
      appropriate. However, it failed to meet basic nutritional guidelines, which was
      reflected in, among other things, unsatisfactory intake of vegetables, fruits,
      oils and water, and in excessive intake of protein of animal origin. In addition,
      it did not cover demands resulting from the perimenopausal period the surveyed
      women were in, which is likely to facilitate, e.g. disorders in lipid metabolism
      and water-mineral balance, as well as development of osteoporosis. CONCLUSIONS:
      The general picture of behaviors, including the nutritional ones, pointed to a
      strong predominance of the diagnosed disease but also to the need of compensating
      for the resultant restrictions, with the latter being perceived by the surveyed
      women as health-promoting actions.

PMID- 22642077
TI  - [The estimation of nutrition habit of ballet school students in Krakow].
AB  - BACKGROUND: There is a considerable cultural pressure towards a slim body
      silhouette. Girls and young woman whose professional carrier depends on their low
      body weight and sharp looking posture are especially vulnerable to such trends.
      This problem is especially acute in girls attending to ballet schools,
      professional dancers and in some sportswoman who are expected to move with charm
      and appear unnaturally slim, usually being the result of special nutrition.
      OBJECTIVE: The aim of this study was the evaluation of the nutritional habits of
      ballet school students and to compare the results with the current nutritional
      norms. MATERIAL AND METHOD: 14 girls, ballet dancers, participated in this study.
      Before the study their body high (BH) and body mass (BM) were measured for the
      calculation of BMI (Body Mass Index). The girls were asked to make notes, during
      10 days, on the amount and kind of food they consumed. The energy and amounts of
      selected nutrients were calculated by the computer program Food 3. RESULTS: The
      results show the deficiency in fats, fibre, minerals like K, Ca, Fe, Mg and some
      vitamins B1 and PP. CONCLUSIONS: Improper diet, deficient in several basics
      nutrients may results in incorrect physical development of attendees of ballet
      schools.

PMID- 22642078
TI  - [Physical activity of elderly people living in district Koprzywnica (Poland)].
AB  - BACKGROUND: Physical activity has good influence on health. The physical activity
      of elderly people may decrease, because of the health problems or think that with
      aging sport activity should be reduced. OBJECTIVE: The aim of the study was to
      assess a physical activity and energy expenditure of people in age 60 and more in
      the Koprzywnica district (Poland). MATERIAL AND METHODS: 95 persons in age 60 and
      more (51 women and 44 men) participated in the study. All participants live alone
      or with family. The following data: total energy expenditure, active energy
      expenditure, physical activity duration (MET > 3,0), vigorous physical activity
      duration (MET > 6,0), number of steps, lying down duration were collected using
      SenseWear Pro3 Armband, Body Media Pittsburgh, USA. The measurement was conducted
      for 24 hours. Physical activity was also classified on the basis of the number of
      steps. RESULTS: The median of the age of participants was 71 years. The median of
      BMI was 27,1 kg/m2. Age was correlated with BMI (R = -0,28, p = 0,005).
      Participants made on average 6335 steps daily, 42% of them made less than 5000
      steps and 31,5% more than 10000 steps a day. The median of the total energy
      expenditure was 33,1 kcal/kg of body mass a day (2522 kcal a day), while the
      median of the active energy expenditure was 5,7 kcal/kg of body mass a day (482
      kcal a day). The median of the physical activity duration was 1 hour and 22
      minutes, and in most cases it was the moderate physical activity. In case of 17
      women (33%) and 20 men (45,5%) the vigorous physical activity was detected, and
      duration of this physical activity was 1-22 minutes. The median of the lying down
      duration was 8 hours and 44 minutes. Older persons had shorter physical activity
      duration, made less steps and at the same time had lower active energy
      expenditure and total energy expenditure than younger ones. There were no
      differences between younger and older participants in the sedentary energy
      expenditure and lying down duration. Simultaneously participants with higher BMI
      compared with participants with lower BMI had shorter physical activity duration
      as well as lower active energy expenditure and total energy expenditure but there
      were no differences in number of steps, lying down duration and sedentary energy
      expenditure between them. CONCLUSIONS: In case of older persons the duration of
      physical activity was shorter and the active energy expenditure was lower than in
      case of younger persons. Both groups had the sedentary energy expenditure and the
      lying duration at the same level. Elderly people with higher BMI had lower total
      energy expenditure and lower intensity and shorter physical activity duration
      than elderly people with lower BMI.

PMID- 22642079
TI  - [Possibilities of preoperative studying of vascular anatomy in surgery of a
      periampullar zone tumors].
AB  - In 115 patients, suffering malignant pancreatic tumors as well as those,
      localized in periampullar zone, a CT angiography was performed preoperatively to
      study up the variants of vascular anatomy. The data obtained were depicted by a
      surgeon, anatomic variants of truncus coeliacus and mesenterical vessels were
      recorded in accordance with classification of Michels, Hiatt. Individualized
      approach for surgical treatment, using CT angiography data, was applied. In 30
      patients the operative intervention with the vessels resection was performed and
      in 6--a no-touch method. Distal pancreatic resection, using the RAMPS technology.
      was performed in 7 patients for malignant tumors. Complications have had occurred
      in 12 (10%) patients, 2 (1.7%) of them died. Lethality after operations with
      vessels resection have constituted 6.6%. The data on variants of vascular
      anatomy, obtained preoperatively, have permitted to escape massive intraoperative
      blood loss with subsequent irreversible necrotic changes in the abdominal cavity
      organs.

PMID- 22642080
TI  - [Endoscopic transpapillary methods of choledocholithiasis treatment, caused by
      presence of multiple calculi].
AB  - The results of endoscopic transpapillary surgical interventions in 115 patients,
      suffering choledocholithiasis, caused by the multiple calculi presence, were
      analyzed. The patients were divided on four groups, depending on the treatment
      provided. In 78 patients (first group) endoscopic papillosphincterotomy with
      mechanical lithoextraction in conjunction with spasmolytic and infusion therapy
      were performed. In 16 patients (second group) endoscopic papillosphincterotomy
      with mechanical lithotripsy and partial lithoextraction, endobiliary stenting
      with further spasmolytic and infusion therapy were performed. In 11 patients (the
      third group) endoscopic papillosphincterotomy, mechanical lithotripsy with a
      partial lithoextraction and nasobiliary drainage were used. In 10 patients (the
      fourth group) endoscopic papillosphincterotomy, mechanical lithotripsy,
      nasobiliary drainage and endobiliary stenting were applied. The best results were
      achieved in the first group: the smallest duration of the operation--(32.2 +/-
      12.6) min, the smallest stationary state duration--(3.3 +/- 1.2) days, the lowest
      rate of intraoperative complications--2.6%.

PMID- 22642081
TI  - [Clinico-morphological substantations of parenchyma-preserving operations
      performance in surgery of chronic pancreatitis].
AB  - There was presented a comparative analysis of the surgical treatment results of
      86 patients, suffering chronic pancreatitis, in whom resection and parenchyma
      preserving elaborated operations were done, aimed for pancreatic and biliary
      ducts hypertension elimination. According to histological and histochemical data
      obtained, there are uniform changes, localized in pancreatic head, corpus and
      tail: the extended periductal fibrosis with the immune-cell infiltration foci and
      periductal connective tissue sheath formation. According to the
      immunohistochemical data obtained, in a fibrous zone there was obtained a big
      quantity of activated alpha-SMA-positive collagen producing star-like cells and a
      significant expression of a type IV collagen. Indications for surgical treatment,
      using parenchyma-preserving procedures, were substantiated, taking into account
      morphological and clinical data present. The patients quality of life in a late
      follow-up period (5 years) after performance of a proposed operative procedure
      (the main group), according to all scales of international questionnaires MOS SF
      36 applied, were trustworthy better (P < 0.05), than after resection procedures
      (control group).

PMID- 22642082
TI  - [The method of calculation of maximally admissable mass of adipose-cutaneous
      flap, excised during abdominoplasty].
AB  - The dependence of a hypercoagulation state occurrence from value of the adipose
      cutaneous flap mass, excised while performing abdominoplasty, was established,
      using the logistic regression method, in patients, suffering the anterior
      abdominal wall cosmetic defects and obesity. The possibility the hypercoagulation
      state occurrence raises nonlinearly together with such of the excised flap mass
      (% EFM), it exceeds 50% (high risk of hypercoagulation occurrence), when the EFM
      value constitutes 5.1% of the body mass.

PMID- 22642083
TI  - [Correction of a connective tissue dysplasia in the treatment of postoperative
      abdominal hernias].
AB  - There were analyzed the results of treatment of 112 patients, suffering
      postoperative abdominal hernia, in whom the anterior abdominal wall alloplasty
      was performed as well as postoperative pathogenetically substantiated complex
      therapy, taking into account the presence of a connective tissue dysplasia
      syndrome (CTDS) and the early and late postoperative complications prophylaxis.
      The peculiarities of postoperative period course and late follow-up results were
      studied up. Phenotypic features of CTDS were revealed in 53 (47.3%) patients,
      immunohistochemical features of a connective tissue dysplasia (a failed collagen
      type I and III ratio, manifested by increase of a collagen type III fibers
      quantity in 3 or more times) were revealed in 78 (69.6%) patients, in whom the
      processes of a collagen and its supermolecular formations synthesis were
      stimulated, using a magnesium orotate (Magnerot), which was prescribed in 1 g
      dose twice a day during 4 - 6 weeks. Application of composite nets, owing big
      pores, in a complex with a postoperative pathogenetically substantiated therapy
      conduction have positively influenced the disease course and the late follow-up
      results achieved.

PMID- 22642084
TI  - [Laparoscopic intraabdominal hernioplasty as the operation of choice in the
      inguinal hernia treatment].
AB  - Comparative analysis of a pain syndrome severity was done, using a visual
      analogous scale (VAS), basing on the analysis of performance of various kinds of
      laparoscopic prosthesis inserting hernioplasty for inguinal hernia, using
      intraabdominal (intraperitoneal onlay mesh - IPOM) and preperitoneal
      (transabdominal preperitoneal - TAPP) with establishment of light nets. A pain
      severity is trustworthy lesser in the IPOM method application--5 and 17.5 points,
      accordingly. The operation duration, using IPOM, have had constituted (60 +/- 20)
      min at average and while using TAPP--(113 +/- 42) min. The stationary
      postoperative state duration after the IPOM procedure was a twice lesser--1.12
      and 2.8 days, accordingly. Laparoscopic prosthesis inserting intraabdominal
      hernioplasty, according to the IPOM method, may constitute the operation of
      choice, performed for inguinal hernia.

PMID- 22642085
TI  - [Comparative estimation of the application efficacy for ceftriaxon and Hepacef
      combi preparations in the abdominal infection treatment].
AB  - A positive experience was described in the work, concerning application of
      Hepacef combi (cefoperazon/sulbactam, manufactured by "ARTERIUM" (Corporation,
      Ukraine) in the treatment of inflammatory-purulent diseases of abdominal organs
      as a method of empirical therapy. There was the preparation action efficacy
      estimated together with the diseases outcomes analysis, and possible
      recommendations for its application suggested. The preparation may be recommended
      for application as the empirical therapy agent in the abdominal infection
      treatment.

PMID- 22642086
TI  - [The symptoms and surgical tactics for complicated forms of the abdominal cavity
      tuberculosis].
AB  - The results of treatment of 12 patients, suffering complicated forms of abdominal
      tuberculosis and external intestinal fistulas, were presented. Late diagnosis of
      abdominal tuberculosis in the patients, suffering the complications phase of the
      disease, is caused by unclear symptoms presence in early stages of the disease.
      Clinical and laboratory indices in peritonitis of a phthisis origin are
      nonspeciphic. In 91% of patients, admitted to the hospital for complicated forms
      of abdominal tuberculosis and external intestinal fistulas, the operative
      treatment was indicated. Surgical intervention (more frequently right-sided
      hemicolectomy, enterostomy, the abscesses opening, the caseously-changed lymph
      nodes excision, formation of anastomosis) was performed in 11 patients for
      peritonitis and external intestinal fistulas. The method of a secure invagination
      anastomoses formation was elaborated, permitting to perform primary restoration
      operations. An early diagnosis, early effective therapy and radical surgical
      intervention conduction for complicated abdominal tuberculosis promote the
      patients to survive.

PMID- 22642087
TI  - [A role of D-dimer and fibrinopeptide A in diagnosis of a hemostasis system
      disorders].
AB  - The investigations, concerning detection of the hemostasis system activation,
      were done in 26 patients, suffering various critical morbid states (an acute
      pancreatitis). The contents of products of the enzymes lysis of coagulation
      system and fibrinolytic system constitute one of the most precise indices.
      Fibrinopeptid A (FpA) is considered one of the most secure indices, confirming
      intravascular thrombin formation, and D-dimer--of a fibrin formation. In the
      patients examined a trustworthy increase of a D-dimer and FpA contents was
      registered, witnessing the hemostasis system activation in an acute pancreatitis
      as well as an excessive formation and lysis of fibrin. D-dimer and FpA contents
      in a plasma constitutes an important diagnostic index, its determination secures
      the possibility of early diagnosis and control of a hemostasis system disorders.

PMID- 22642088
TI  - [Diagnosis and treatment of postintubation tracheal stenosis].
AB  - There was analyzed the experience of diagnosis and surgical treatment of 61
      patients, aged from 2 to 69 years old, including 43 (70.5%) men and 18 (29.5%)
      women, in whom after a tracheal intubation with durable pulmonary ventilation,
      performed for an acute respiratory insufficiency, a tracheal stenosis have had
      occurred. A tracheal stenosis was manifested by a stridorous kind of respiration,
      the diagnosis was confirmed by the endoscopic investigation and a computer
      tomography data. Conservative and endoscopic treatment was effective in 10
      (16.4%) patients, operative intervention--circular resection with a primary
      tracheal anastomosis formation and a staged treatment with tracheostomy and a T
      kind silicone tube insertion--was performed in 51 (83.6%) patients. Good and fair
      results were achieved in 70% of the patients.

PMID- 22642089
TI  - [Surgical treatment of a wound defects of torso and extremities].
AB  - The results of examination and treatment of 179 patients, suffering the wound
      defects, localized on corpus and extremities, were presented. The patients were
      divided on groups, depending on the etiology of the defect, they were examined in
      accordance to algorithm proposed. Ultrasound duplex scanning was applied for
      diagnosis of regional hemodynamics disorders with the objective to choose a
      correcting intervention and investigation of a donor site vessels. The surgical
      tactics choice have depended on anatomic-functional and hemodynamical
      peculiarities of the affected locus present. In all the patient a microbiological
      monitoring of wounds was conducted and a rational antibioticotherapy prescribed.

PMID- 22642090
TI  - [Anatomic-topographic peculiarities of sub- and supratentorial petroclival
      meningiomas].
AB  - The data about anatomic-topographic peculiarities of petroclival sub- and
      supratentorial meningiomas were presented. There were operated on 24 patients, of
      them 5 have died. Three main topographoanatomic variants were delineated,
      depending on the tumor primary origin and topographic peculiarities present. The
      most frequent variant of the tumor localization was a lower one. Depending on the
      variant of the tumor localization present, the peculiarities of interrelationship
      between the tumor and nerves, vessels and the brain stem are determined.

PMID- 22642091
TI  - [Anesthesiological support of operative interventions in the injured persons,
      suffering a cold trauma].
AB  - Basing on analysis of the treatment results in 74 injured persons with a cold
      trauma there was proved, that during operative interventions performance a total
      intravenous anesthesy and a spinal cord anesthesy are used most frequently.
      Inhalation anesthesy and conducting methods of anesthesy ought to be used more
      frequently, because a total intravenous anesthesy is a lesser guided one and a
      spinal cord anesthesy may cause a severe hypotension in the injured persons.

PMID- 22642092
TI  - [Cytokines as biomarkers of the patients state severity and prognostication in
      burns: new therapeutic possibilities of existing approaches in treatment. Part
      2].

PMID- 22642093
TI  - [A Baker cyst: pathogenesis, diagnosis, treatment].

PMID- 22642094
TI  - [Complex conservative treatment of idiopathic scoliosis].

PMID- 22642095
TI  - [A first experience of performance of a sigmoid colon laparoscopic resection,
      using a single transumbilical access].

PMID- 22642096
TI  - [Skin restoration, using microautodermotransplants in the injured persons with
      widespread deep burns].

PMID- 22642097
TI  - [Nucleosomes in gene regulation: theoretical approaches].
AB  - This work reviews current theoretical approaches of biophysics and bioinformatics
      for the description of nucleosome arrangement in chromatin and transcription
      factor binding to nucleosomal organized DNA. The role of nucleosomes in gene
      regulation is discussed from molecular mechanistic and biological point of view.
      In addition to classical problems of this field, actual questions of epigenetic
      regulation are mentioned. The authors selected for discussion what seem to be the
      most interesting concepts and hypotheses. Mathematical approaches are described
      in a simplified language to attract attention to the most important directions of
      this field.

PMID- 22642099
TI  - [Structure and function of enteric alpha defensins in norm and pathology].
AB  - This review summarizes currently available data on enteric alpha defensins
      structure, their functions in the innate and adaptive immunity systems and the
      role in development of intestinal illnesses.

PMID- 22642098
TI  - [Molecular mechanisms of peroxisome biogenesis in yeasts].
AB  - Peroxisomes contain oxidases generating hydrogen peroxide, and catalase degrading
      this toxic compound. Another characteristic function of each eukaryotic
      peroxisome, from yeast to man, is fatty acid beta-oxidation. However, in
      peroxisomes a variety of other metabolic pathways are located. In fungi,
      peroxisomes contain enzymes involved in catabolism of unusual carbon and nitrogen
      sources (methanol, purines, D-amino acids, pipecolynic acid, sarcosine,
      glycolate, spermidine etc) as well as biosynthesis of lysine in yeasts and
      penicillin in mycelial fungi. Impairment of peroxisomal structure and functions
      causes many human disorders. The similar defects have been identified in yeast
      mutants defective in peroxisomal biogenesis. Peroxisomal biogenesis is actively
      studied during last two decades using uni- and multicellular model systems. It
      was observed that many aspects of peroxisomal biogenesis and proteins involved in
      this process display striking similarity between all eukaryotes, from yeasts to
      humans. Yeast is a convenient model system for this kind of research. Current
      review summarizes data on molecular events of peroxisomal biogenesis, functions
      of peroxine proteins, import of peroxisomal matrix and membrane proteins and on
      mechanisms of peroxisomedivision and inheritance.

PMID- 22642100
TI  - [Formation of spatial structure of RNA molecules].
AB  - In this review we consider several experimental and theoretical approaches for
      investigation of RNA folding and determination of nucleotides that play an
      important role upon folding of such molecules as tRNA and several classes of
      ribozymes. It has been shown that nucleotides in the D- and T-loop regions are
      the last to be involved in tRNA structure or they are not included in the folding
      nucleus of tRNA. Using the specially elaborated method SHAPE it has been
      demonstrated that the model of hierarchical folding which was recognized for a
      long time is not correct for tRNA folding. In the second part of the given review
      the algorithms and programs used for the prediction of secondary structures of
      RNA as well as for modeling of RNA folding are considered.

PMID- 22642101
TI  - [DNA-topoisomerases and their functions in cell].
AB  - DNA-topoisomerases are sophisticated enzymes controlling DNA topology in cells. A
      lot of new data concerning the structure and functions of topoisomerases was
      published recently. In this review authors discuss basic features of the
      different types of topoisomerases with respect to catalytic mechanism and focus
      at the involvement of topoisomerases in various DNA-related cellular processes,
      such as replication, transcription, recombination, chromatin condensation and
      daughter chromatides partitioning.

PMID- 22642102
TI  - Efficiency of ligation-mediated PCR and TAIL-PCR methods for isolation of RbcS
      promoter sequences from green microalgae Ankistrodesmus convolutus.
AB  - Isolation of promoter sequences from known gene sequences is a tedious task in
      genome-related research. An efficient method of obtaining the promoter sequences
      is necessary in order to successfully use targeted promoters for genetic
      manipulations. Here, efficiency and usefulness of two PCR-based methods, namely:
      ligation-mediated PCR and thermal asymmetric interlaced (TAIL) PCR, for isolation
      of promoter sequences of the ribulose-1,5-bisphosphate carboxylase/oxygenase
      small subunit (RbcS) gene from green microalgae Ankistrodesmus convolutus (A.
      convolutus) were evaluated. The results showed that the amplification efficiency
      of TAIL-PCR was higher than that of the ligation-mediated PCR method, i.e. the
      amplified promoter fragments of 1.2 and 0.8 kb in length or promoter sequences of
      813 and 606 bp (after eliminating the unreadable sequences). The use of TAIL-PCR
      described here presents a low cost and efficient strategy for the isolation of
      promoter sequences of known genes, especially in GC-rich regions, and species
      with little or no available genome information such as A. convolutus.

PMID- 22642103
TI  - [Localization of point mutations in the coding part of the VHL gene in clear cell
      renal cancer].
AB  - VHL gene is often inactivated in sporadic clear cell renal cancer (CCRC) due to
      somatic mutations, and it's germline mutations cause hereditary CCRC--von Hippel
      Lindau syndrome. Localization of mutations in VHL, identification of new
      mutations and their influence on CCRC progression and sensitivity to targeted
      therapy are actual problems in modern oncogenetics. We have provided search and
      characterization of mutations in 248 primary CCRC using SSCP-analysis and
      sequencing. Somatic mutations were detected in 37.5% of samples, 72% of mutations
      were identified for the first time. New missense-mutations were analyzed by
      alignment programs and three-dimensional structure modeling. Mutation frequency
      was compared in different groups of patients in respect to stage, grade, and
      metastases. It was demonstrated that 39.1% samples with stage I harbor somatic
      mutations, however, no association with progression or metastases was found. We
      also have investigated localization of mutations in the VHL coding part and
      positions of missense-mutations and inframe deletions/insertions focusing on VHL
      critical sequences. VHL mutation analysis performed in this study improve the
      possibilities of laboratory diagnostics of familial and sporadic CCRC.

PMID- 22642104
TI  - [Molecular evolution of the tick-borne encephalitis and Powassan viruses].
AB  - The problem of emerging viruses, their genetic diversity and viral evolution in
      nature are attracting more attention. The phylogenetic analysis and evaluationary
      rate estimation were made for pathogenic flaviviruses such as tick-borne
      encephalitis virus (TBEV) and Powassan (PV) circulated in natural foci in Russia.
      47 nucleotide sequences of encoded protein E of the TBEV and 17 sequences of NS5
      genome region of the PV have been used. It was found that the rate of
      accumulation of nucleotide substitutions for E genome region of TBEV was
      approximately 1.4 x 10(-4) and 5.4 x 10(-5) substitutions per site per year for
      NS5 genome region of PV. The ratio of non-synonymous nucleotide substitutions to
      synonymous substitution (dN/dS) for viral sequences were estimated of 0.049 for
      TBEV and 0.098 for PV. Maximum value dN/dS was 0.201-0.220 for sub-cluster of
      Russian and Canadian strains of PV and the minimum - 0.024 for cluster of Russian
      and Chinese strains of Far Eastern genotype TBEV. Evaluation of time intervals of
      evolutionary events associated with these viruses showed that European subtype
      TBEV are diverged from all-TBEV ancestor within approximately 2750 years and the
      Siberian and Far Eastern subtypes are emerged about 2250 years ago. The PV was
      introduced into natural foci of the Primorsky Krai of Russia only about 70 years
      ago and PV is a very close to Canadian strains of PV. Evolutionary picture for PV
      in North America is similar to evolution of Siberian and Far Eastern subtypes
      TBEV in Asia. The divergence time for main genetic groups of TBEV and PV are
      correlated with historical periods of warming and cooling. These allow to propose
      a hypothesis that climate changes were essential to the evolution of the
      flaviviruses in the past millenniums.

PMID- 22642105
TI  - [Polymorphic variants of genes encoding interleukin-6 and fibrinogen, the risk of
      ischemic stroke and fibrinogen levels].
AB  - Carriage frequencies of alleles and genotypes of polymorphous locus of -174G>C
      IL6 (rs1800795) were analyzed in the patients with ischemic stroke (IS) of
      Russian ethnic descent (200 cases) and in the control group of the same ethnic
      descent with similar sex and age (140 controls). Significant differences were
      identified in frequencies of carriage (in homo- or heterozygous form) of allele
      IL6*-174G (p = 0.0029, OR = 2.9, 95% CI: 1.4-5.8), which can be considered as
      risk factor for IS and in frequencies of IL6*-174C/C genotype carriage,
      correspondingly (p = 0.0029, OR = 0.35, 95% CI: 0.17-0.69). After sex
      stratification of patients and controls similar significant differences were
      observed only between female patients and controls, after age stratification the
      difference was observed only for the age group older 60 years. Complex analysis
      of association of SNP -174G>C IL6 alleles and genotypes carriage in combination
      with SNP 4266A>G (Thr312Ala) FGA (rs6050) (see symbol) -249C>T FGB (rs1800788)
      with IS revealed protective combinations IL6*-174C/C + FGA* 4266A (see symbol)
      IL6*-174C/C + FGB*-249C, which were slightly more significant than single
      protective genotype IL6*-174C/C associated with IS and their ORs didn't differ
      substantially from the single genotypes's OR value. At the same time the
      combinations of alternative allele IL6*-174G with the same FGB*-249C or FGA*
      4266A alleles were revealed and their association significance levels as well as
      OR values were lower than the values for the single risk allele IL6*-174G. In
      case of the mutual carriage of IL6*-174G allele with FGA*4266A/A, FGB*-249C/C
      genotypes or with combinations of these alleles/genotypes the "neutralized"
      effect became stronger. In other words, we observed association of IS with
      allele/genotype combinations of genes IL6, FGA and FGB, in which IL6 plays key
      role and FGA and FGB have modulating function. In analysis of association of
      fibrinogen plasma levels with three analyzed polymorphous loci significant
      differences were not revealed.

PMID- 22642106
TI  - [Polymorphisms in xenobiotic-metabolizing genes in the pathogenesis of
      glucocorticoid-induced osteoporosis in patients with bronchial asthma].
AB  - Search for and study of risk factors for glucocorticoid-induced (GI)
      osteoporosis, as one of the most frequent and serious complications of long-term
      systemic glucocorticoid (SGC) therapy for bronchial asthma are an important
      problem of prevention medicine. In the present work to determine the frequencies
      of genotypes and alleles of eight candidate genes of GI osteoporosis in 137
      patients with bronchial asthma receiving long-term SGC therapy, using allele
      specific hybridization on the biochip. In the analysis of gene polymorphism MTHFR
      677C>T showed a statistically significant association between genotypes for this
      gene and proximal femur mineral density (BMD) for the Z-criterion in patients
      treated with SGC (non-parametric ANOVA Kruskal-Wallis p = 0.0013). In addition,
      the analysis of insertion-deletion polymorphism of GSTM1 found that carriers of
      GSTM1 "null" genotype have lower values of BMD Z-criterion, than carriers of at
      least one functional allele of GSTM1 gene (Mann-Whitney U-test with Bonferroni
      correction, p = 0.034). Analysis of gene-gene interactions revealed that carriers
      of MTHFR genotype 677C/C in combination with GSTM1 "null" genotype characterized
      by a statistically significant lower values of BMD Z-criterion, than carriers of
      other variants of genotypes (ANOVA Kruskal-Wallis, p = 0.0012). Thus, the alleles
      of MTHFR and GSTM1 genes may modulate the risk of GI osteoporosis in patients
      with bronchial asthma, which is very important to identify group of patients with
      high risk for osteoporosis among individuals receiving SGC as well as inhaled
      glucocorticoids.

PMID- 22642107
TI  - Rarity of tagSNPs across transferred mtDNA inserts in human genome.
AB  - The study deals with the single nucleotide polymorphism (SNPs, HapMap data)
      around the mtDNA insertions in human genome. The results obtained from this study
      suggest that application of tagSNP approach for large scale genotyping targeting
      NUMT integration sites may be difficult due to lack of informative mutations
      around these loci. This warrants development of new approaches to tag mtDNA
      inserts in genome-wide association studies.

PMID- 22642108
TI  - [NBS-ARC domain variability of Rx1 homologues of cultivated potato and related
      wild species].
AB  - In the present work NBS-ARC domain sequences of Rx1 homologues of ten accessions
      of cultivated and wild potato species which differ in susceptibility to potato
      virus X were obtained and studied. Within the NBS-ARC domain different indels and
      nucleotide/amino acid substitutions, including substitutions in the conservative
      motives of the domain were detected. There were no direct associations between
      the mutational changes found in the conservative motives of the NBS-ARC domain
      and the susceptibility of the studied accessions to X virus.

PMID- 22642109
TI  - Valproic acid decreases the reparation capacity of irradiated MOLT-4 cells.
AB  - The aim of our work was to evaluate mechanisms leading to radiosensitization of
      MOLT-4 leukemia cells following valproic acid (VA) treatment. Cells were
      pretreated with 2 mM VA for 24 h followed by irradiation with a dose of 0.5 or 1
      Gy. The effect of both noxae, alone and combined, was detected 1 and 24 hours
      after the irradiation. Induction of apoptosis was evaluated by a flow cytometry.
      The extent of DNA damage was further determined by phosphorylation of histone
      H2AX using confocal microscopy. Changes in protein expression were identified by
      SDS-PAGE/immunoblotting. Two-millimolar VA increased apoptosis induction after
      irradiation as well as phosphorylation of H2AX and provokes an increase in the
      level of p53 and its phosphorylation at Ser392 in 4 h post-irradiation. Likewise,
      p21 protein reached its maximal expression in 4 h after the irradiation of VA
      treated cells. Twenty four hours later, only the p53 phosphorylated at Ser15 was
      detected. At the same time, the protein mdm2 (negative regulator of p53) was
      maximally activated. The 24-hour treatment of MOLT-4 leukemia cells with 2 mM VA
      results in radiosensitizing, increases apoptosis induction, H2AX phosphorylation,
      and also p53 and p21 activation.

PMID- 22642110
TI  - [Functional properties of the WNT11 new isoform, expressed in colon carcinoma
      cell line HT29].
AB  - Colon carcinoma is a common type of neoplastic transformation. Mechanisms of its
      establishment and progression have been studying for several decades. Aberrant
      activation of the canonical Wnt signaling is frequently observed in colon
      carcinoma cells. Moreover, expression of the "noncanonical" Wnt ligands is also
      detected in this type of cancer. However, the implication of the noncanonical Wnt
      signaling in carcinogenesis and colorectal cancer (CRC) progression is still
      unclear. Here, to elucidate the characteristic features of the noncanonical Wnt
      signaling activation in CRC the expression of the "noncanonical" ligand hWnt11
      has been studied. It was shown for the first time that expression of the hWnt11
      in CRC is accompanied by the alternative splicing. The new hWnt11 isoform
      (hWnt11sp3) has been identified. Unlike to hWnt11, this isoform is not secreted
      and lacks the ability to inhibit the canonical Wnt signaling. Considering the
      canonical Wnt signaling inhibiting activity of hWnt11, different functional
      properties of the ligand and its isoform may reflect a special role of the
      alternative splicing in carcinogenesis and tumor progression. Thus, due to the
      difference in their functional properties an existence of several Wnt isoforms
      should be taken into account for the investigation of the role of Wnt ligands.

PMID- 22642111
TI  - [P66shc action on resistance of colon carcinoma RKO cells to oxidative stress].
AB  - P66shc protein is an alternative transcript product of SHC1 gene. While two other
      isoforms (p52shc and p46shc) have adaptor function in RAS signaling pathway,
      p66shc regulates reactive oxygen species (ROS) level. P66shc genome knockout
      significantly extends lifespan in mice. Though p66shc was determined to
      translocate into mitochondria and led to increase in intracellular ROS, the
      mechanism by which the protein take part in signaling pathways that regulates
      resistance to cellular stresses remains poorly studied. P66shc has an important
      role in carcinogenesis and its increased expression correlates with poor
      prognosis in colon cancer. In this work we have applied RNA interference using
      lentiviral constructions that express short hairpin RNA (shRNA) against N
      terminal CH2 domain of p66shc isoform. Using this approach p66 but not p52 and
      p46 SHC1 isoform expression was selectively suppressed in colon carcinoma RKO
      cells. RKO cells with p66shc knockdown have shown to be more resistant to
      oxidative stress induced by hydrogen peroxide or serum starvation. Fragmentation
      of mitochondria that depends on mitochondrial ROS accumulation during oxidative
      stress was significantly decreased in this cells. The data obtained are in
      agreement with hypothesis that p66shc participates in ROS accumulation in
      mitochondria and by this means promotes induction of apoptosis.

PMID- 22642112
TI  - [A feedback between membrane fluidity and transcription of the desB gene for the
      omega3 fatty acid desaturase in the cyanobacterium Synechocystis].
AB  - Prokaryotic cells, including cyanobacteria, respond to a decrease in ambient
      temperature by activation of numerous cold shock genes. Low temperatures cause a
      decrease in membrane fluidity, which is maintained at some optimal level mainly
      by fatty acid (FA) desaturases. Here, temperature-dependent expression of the
      desB gene for the omega3-desaturase in Synechocystis, which synthesized
      polyunsaturated FAs, and in its mutant, desA-/desD-, which is defective in genes
      for delta12- and delta6-desaturases and is capable of synthesizing only
      monounsaturated FAs was studied. Low temperatures caused the increase in the
      amount of the desB mRNA in the wild-type cells with the maximum observed at 24
      degrees C. In the double mutant desA-/desD- cells, the maximum amount of this
      mRNA was accumulated at 28-30 degrees C. Thus, our studies of the desB gene for
      the omega3-desaturase demonstrated that temperature-dependent expression of
      genes, which are responsible for the maintenance of the optimal membrane
      fluidity, depends on physical state of these membranes and is regulated by a
      feedback mode.

PMID- 22642113
TI  - The conformational polymorphism of the green fluorescent protein.
AB  - Green fluorescent protein (GFPuv) has been widely used as a reporter fused to
      individual targeting sequences. However, its state in liquid and its effect on
      other proteins are still unclear. The conformational polymorphisms of glutathione
      S-transferase-green fluorescent protein (GST-GFPuv), GFPuv and GST were analyzed
      by native polyacrylamide gel, indicating that GST was in many different states
      while GFPuv and GST-GFPuv were only in four and two slightly different states.
      Four different circular dichroism spectra were obtained from the GFPuv
      polymorphisms. The single molecular behavior of GST-GFPuv and GFPuv was also
      characterized by MALDI-TOF MS. Thus, we demonstrated that: (1) there might be
      four different structural polymorphisms for the native GFPuv; (2) GFPuv could
      reduce its partner's polymorphism as a fusion protein. Although GFPuv had many
      merits as a reporter, its unreliability was found in the study.

PMID- 22642114
TI  - Creatine ethyl ester: a new substrate for creatine kinase.
AB  - The creatine kinase/phosphocreatine system plays a key role in cell energy
      buffering and transport, particularly in cells with high or fluctuating energy
      requirements, like neurons, i.e. it participates in the energetic metabolism of
      the brain. Creatine depletion causes several nervous system diseases, alleviated
      by phosphagen supplementation. Often, the supplementation contains both creatine
      and creatine ethyl ester, known to improve the effect of creatine through an
      unknown mechanism. In this work we showed that purified creatine kinase is able
      to phosphorilate the creatine ethyl ester. The K(m) and V(max) values, as well as
      temperature and pH optima were determined. Conversion of the creatine ethyl ester
      into its phosphorylated derivative, sheds light on the role of the creatine ethyl
      ester as an energy source in supplementation for selected individuals.

PMID- 22642115
TI  - [Selection of reliable reference genes for qRT-PCR analysis in human non
      cancerous gastric tissue].
AB  - Real-time PCR (qRT-PCR) is the standard method for studying changes in relative
      gene expression in complex diseases like obesity and gastritis. However,
      variations in amount of starting material, enzymatic efficiency and presence of
      amplification inhibitors can lead to quantification errors. Hence, the need for
      accurate data normalization is vital. Among several known strategies for data
      normalization, the use of reference genes as an internal control is the most
      common approach. Human gastric tissue has been the least investigated for
      stability of reference gene expression. In this study, three popular algorithms,
      GeNorm, NormFinder and BestKeeper were used to evaluate the reference gene
      stability. CONCLUSION: HPRT1 and GAPDH are the best performing pair of reference
      genes for qRT-PCR profiling experiments involving non-malignant gastric tissue
      samples.

PMID- 22642116
TI  - [A fast algorithm to build a supertree with a set of gene trees].
AB  - Important desired properties of an algorithm to construct a supertree (species
      tree) by reconciling input trees are its low complexity and applicability to
      large biological data. In its common statement the problem is proved to be NP
      hard, i.e. to have an exponential complexity in practice. We propose a
      reformulation of the supertree building problem that allows a computationally
      effective solution. We introduce a biologically natural requirement that the
      supertree is sought for such that it does not contain clades incompatible with
      those existing in the input trees. The algorithm was tested with simulated and
      biological trees and was shown to possess an almost square complexity even if
      horizontal transfers are allowed. If HGTs are not assumed, the algorithm is
      mathematically correct and possesses the longest running time of n3 x[V0]3, where
      n is the number of input trees and [V0] is the total number of species. The
      authors are unaware of analogous solutions in published evidence. The
      corresponding inferring program, its usage examples and manual are freely
      available at http://lab6.iitp.ru/en/super3gl. The available program does not
      implement HGTs. The generalized case is described in the publication "A tree
      nearest in average to a set of trees" (Information Transmission Problems, 2011).

PMID- 22642117
TI  - [Occurrence of motifs with six amino acid residues in three eukaryotic
      proteomes].
AB  - Now it is known that 18 neurological inherited diseases connected with mutations
      of multiple insertion of one amino acid residue in protein sequence. Therefore,
      studying the functional role of such simple motifs is an important task in
      biology. In this work we have investigated how often homorepeats, i.e. runs of a
      single amino acid residue, of 6 amino acid residues long as well as simple motifs
      consisting from two amino acid residues of 6 residues long situated in any
      position occur in three eukaryotic well studied proteomes: Homo sapiens,
      Drosophila melanogaster, Caenorhabditis elegans. It turns out that many simple
      motifs occur very often. The occurrence for each motif can be found at our site:
      http://antares.protres.ru/motifs_six_residues.html. One can suggest that such
      short similar motifs are responsible for the common functions for nongomologous,
      unrelated proteins from different organisms.

PMID- 22642118
TI  - [Structure and properties of proprotein convertase inhibitors].
AB  - This review is devoted to structure and properties of proprotein convertases
      (PCs), the intracellular Ca(2+)-dependent serine endoproteases of mammalia, that
      play the essential role in the processing of inactive protein precursors and
      their transforming into bioactive mature products. PCs are also implicated in
      development of a great variety of diseases including bacterial or viral
      infections and such pathologies as cancer, Alzheimer's disease, obesity and so
      on. Owing to these findings, PCs are considered as promising targets for design
      of their inhibitors and development of new potential therapeutic agents. Only
      several endogenous protein inhibitors are identified now for PCs: pro7B2
      (Proprotein 7B2), the specific chaperon of PC2, granine-like precursor of
      neuroendocrine protein proSAAS, the selective ligand of PC1, and serpin Spn4A
      (Serine Proteinase Inhibitor) of Drosophila melanogaster that inhibits PC2 and
      furin. By the methods of site-directed mutagenesis, the bioengineered inhibitors
      of PCs were also designed. Structures and properties of protein or peptide
      fragments as inhibitors of PCs were also discussed. Particularly, the properties
      of polyarginines and small peptides containing pseudopeptide bond at the scissile
      site a suitable peptide substrate were described. The inhibitory activity of non
      peptide compounds such as derivatives of andrographolid from Andrographis
      paniculata (K(i) = 2.6-200 microM against furin), certain complexes of pyridine
      analogs with ions of Cu2+ or Zn2+ inhibiting furin with IC50 = 5-10 microM,
      derivatives of 2,5-dideoxy-streptamine containing several guanidine groups (K(i)
      = 6-812 nM for furin) and also a number of dicoumarols (K(i) = 1-185 microM
      against furin) and some flavonoids (with K(i) = 5-230 microM for furin) were
      reflected in the article. The effects of enediynyl-amino acids derivatives or
      their peptides (K(i) = 40 nM against furin) were considered. Inhibition of PC2 by
      N-acylated bicyclic guanidines (K(i) = 3.3-10 microM) or derivatives of
      pyrrolidin bispyperazines (K(i) = 0.54-10 microM) are considered too. Some of
      synthesized derivatives may serve as lead compounds for design of the specific
      inhibitors for individual PCs.

PMID- 22642119
TI  - [Influence of metal ions and specific chemical reagents on activity of alpha-L
      rhamnosidase of Eupenicillium erubescens].
AB  - The effect of cations, anions and specific chemical reagents: 1-[3
      (dimethylamino) propyl]-3-ethylcarbodiimide methiodide, EDTA, o-phenanthroline,
      dithiotreitol, L-cysteine, beta-mercaptoethanol, p-chlormercurybenzoate (p-ChMB),
      N-ethylmaleimide on the activity of alpha-L-rhamnosidase of Eupenicillium
      erubescens has been investigated. The essential role of Ag+ and Hg2+ which
      inhibit the alpha-L-rhamnosidase activity by 47-73% has been shown. Whereas L
      cysteine exhibits the protective effect, rhamnose in concentration of 1-5 mM does
      not protect the enzyme from negative effect of Ag+ and Hg2+. Basing on the
      inhibitory and kinetic analysis it was supposed that the carboxyl group of C
      terminal aminoacid and imidazole group of histidine take part in the catalytic
      action of alpha-L-rhamnosidase. It was assumed that sulphydryl groups took part
      in catalysis, carried out by alpha-L-rhamnosidase of E. erubescens, since the
      activity of alpha-L-rhamnosidase inhibited by p-ChMB and thiol reagents such as
      dithiothreitol, L-cysteine, beta-mercaptoethanol did not remove its inhibitory
      action.

PMID- 22642120
TI  - [Activity of enzymatic detoxification systems in the mice liver under conditions
      of different retinoid provision].
AB  - The activity of cellular components of liver detoxification system was studied
      under the conditions of the absence of vitamin A stores. It is shown that a
      decrease of p-hydroxylase and N-demethylase activity of cytochrome P-450
      simultaneously with a decrease of glutathione-S-transferase activity takes place
      in the liver microsomal fraction of vitamin A-deficient animals. At the same time
      the absence of retinoid stores in knock-out animals influences the decrease of
      only p-hydroxylase activity of cytochrome P-450 system. The increase in
      glutathione-S-transferase activity is observed in the liver postmicrosomal
      fraction in mice, kept on vitamin A-deficient diet, while its parametres in knock
      out group animals were not statistically different compared to the control.

PMID- 22642121
TI  - [Generation of active oxygen forms in rat thymocytes under action of hydrogen
      peroxide and fullerene C60].
AB  - The dynamics of active oxygen forms (AOF) generation in rat thymocytes 50 min
      after treatment with 0.1 and 0.5 mM H2O2 was estimated with the use of
      fluorescent probe DCFDA. Both enhanced AOF generation, which was dependent on
      H2O2 concentration, and glutathione peroxidase and superoxide dismutase
      activation, followed by a decrease of thymocytes viability were demonstrated.
      Preincubation of cells with 10(-5) M fullerene C60 was shown not only to prevent
      H2O2--induced AOF generation but to increase viability of H2O2-treated thymocytes
      at more prolonged time period. The data obtained indicate to fullerene C60
      ability to prevent oxidative stress in thymocytes.

PMID- 22642122
TI  - [Effect of selenium on resistance of hemoglobin to photooxidative processes].
AB  - On an example of a guinea pig it is shown that exogenous selenium (0.5 mg Na2SeO3
      per 1 kg of the animal weight) during 2-hour exposition in the animal organism
      increases the resistance to the photo-induced oxidation of haemoglobin in
      erythrocyte lysates without additional stimulation of glutathione peroxidase
      mechanism of haemoglobin protection by exogenous selenium. It is shown that the
      saturation of haemoglobin fractions by selenium hampers the oxidative
      modification of haemoglobin. Using pregnancy of women as a natural model of
      selenium-deficiency condition, it has been shown that physiological debilitation
      of saturation erythrocytes with selenium, including haemoglobin fractions of
      lysates erythrocytes caused debilitation of resistance of haemoglobin to
      photooxidative destruction. Under these conditions not only activity of enzyme
      glutathione peroxidise in erythrocyte lysates, but also the peroxidase activity
      of haemoglobin (in the presence of glutathione) were decreased. It is more
      characteristic of erythrocyte lysates with a less content of selenium, i.e. for
      the erythrocytes of women on late terms of pregnancy that testifies to the
      presence of certain relation between haemoglobin saturation with selenium and its
      peroxidase activity (in the presence of glutathione).

PMID- 22642123
TI  - [Studies by means of 1H NMR spectroscopy of complex formation of aromatic
      biologically active compounds with antibiotic topotecan].
AB  - The analysis of heteroassociation of antibiotic topotecan (TPT) with aromatic
      biologically active compounds (BAC): caffeine, mutagens ethidium bromide and
      proflavine, antibiotic daunomycin, vitamins flavin-mononucleotide and
      nicotinamide, has been carried out in the work using 1H NMR spectroscopy data.
      The equilibrium constants of heteroassociation and induced chemical shifts of the
      protons have been obtained in the complexes with BAC. It is found that the
      complex formation TPT-BAC has the nature of stacking of the chromophores,
      additionally stabilized in the case of proflavine by intermolecular hydrogen
      bond. Calculation of the basic components of the Gibbs free energy of the
      complexation reactions is carried out, and the factors which stabilize and
      destabilize the heterocomplexes of molecules are revealed.

PMID- 22642124
TI  - [Immunomodulatory effects of vitamin D3 and bisphosphonates in nutritional
      osteoporosis in rats].
AB  - The aim of this study was to determine the effectiveness of separate and combined
      administration of vitamin D3 and different forms of bisphosphonate (disodium salt
      of methylenbisphosphonic acid dihydrate and alendronate) on the function of
      immune cells in rats with nutritional osteoporosis. It was shown that D
      hypovitaminosis leads to reduced 25OHD3, which is a biomarker for vitamin D3 and
      disturbances of metabolic processes in bone tissue that correlated with
      osteoporosis manifestation. Immunologic disorders related to nutritional
      osteoporosis were accompanied by the decrease in phagocytic activity of
      granulocytes and impaired ability to produce bactericidal oxidants. Inhibition of
      B-cell immunity also occurred in patholgy. Thus, the present study revealed more
      pronounced immunomodulatory effects of vitamin D3 on phagocytic immunity, whereas
      bisphosphonates were effective in improving the humoral immune protection.

PMID- 22642125
TI  - [Nicotinamide influence on pancreatic cells viability].
AB  - The study was undertaken to investigate the modulating effect of nicotinamide
      (NAm) in different concentrations and under different glucose concentrations on
      the viability and oxidative stress induced by streptozotocin (STZ, 5 mmol/l) and
      hydrogen peroxide (H2O2, 100 micromol/l) on isolated rat pancreatic cells of the
      Langerhans islets in vitro. Cell viability did not depend on the concentration of
      glucose in the range of 5-20 mmol/l, and in subsequent studies we used glucose in
      concentration of 10 mmol/l to protect cells against its hypo- and hyperglycemic
      action. Cytoprotective effect of NAm in concentrations from 5 to 20 mmol/l on
      cells survival was the same. It was found that the destructive action of STZ and
      H2O2 during 24 hours on isolated cells of the pancreas resulted in the
      significant cell death. It was revealed that NAm in concentration of 5 mmol/l not
      only had cytoprotective effects against STZ and H2O2 but also partially reduced
      the level of oxidative stress in the investigated cells induced by these
      compounds. High concentration of NAm, 35 mmol/l, causes cytotoxic effect on the
      viability of pancreatic islet cells and increase of oxidative stress induced by
      STZ and H2O2. Most likely these effects could be associated with direct
      modulatory action of NAm on important effector mechanisms involved in cell death,
      including PARP-dependent processes, or/and indirectly, through metabolic and
      antioxidant effects of the compound.

PMID- 22642127
TI  - [On true and apparent Michaelis constants in enzymology. II. Is the equation
      k(m)app = k(s) + k)cat)/k(1) true for enzyme-catalysed reactions with activator
      participation?].
AB  - The article is dedicated to analysis of equation which expresses apparent
      Michaelis constant K(m)app) of enzyme-catalysed reactions with activator
      participation by means of the substrate constant K(s) and rate constant of enzyme
      substrate complex decomposition k(cat). It has been shown that although it is
      possible to record the mechanisms of such reactions as a scheme similar to
      Michaelis-Menten model and to derive equation of apparent Michaelis constant as
      K(m(app) = K(s) + k(cat)/k(1), but this approach cannot be used for investigation
      of all reactions with activator participation. The equation mentioned above is
      not obeyed in the general case, it may be true for some mechanisms only or under
      certain ratio of kinetic parameters of enzyme-catalysed reactions.

PMID- 22642126
TI  - [Effect of N-stearoylethanolamine(NSE) on activity of angiotensine-converting
      enzyme in the brain structures and blood plasma of rats with streptozotocine
      induced diabetes].
AB  - The influence of saturated N-acylethanolamine--N-stearoylethanolamine (NSE) on
      the activity of angiotensine-converting enzyme (ACE) in the brain structures of
      rats with streptozotocine-induced diabetes was studied. It was shown that
      decreased activity of ACE was observed in the hypothalamus, increased--in the
      anterior pituitary. The NSE suspension administration to rats with experimental
      diabetes in a dose 50 mg/kg of body weight during 10 days caused a decrease in
      ACE activity in the anterior pituitary, whereas in the hypothalamus and
      hippocampus ACE activity did not change significantly. At the same time,
      introduction of NSE to intact animals led to the reduction of activity of ACE in
      the hippocampus, anterior pituitary and blood plasma. It is known that the
      highest amount of ACE in the brain structures is located in the membrane-bound
      state. Thus, the changes we have found in the activity of ACE in the control rats
      and in animals with induced diabetes may be related to the ability of NSE to the
      modulation of cell membranes lipid profile. Changes in the activity of ACE under
      the action of N-acylethanolamines may be one of the mechanisms for implementation
      of anti-hypertensive and anti-inflammatory action of these compounds.

PMID- 22642128
TI  - [Analysis of titration curves of serum antibodies obtained by ELISA].
AB  - Different forms of titration curves obtained by ELISA for serum antibodies,
      monoclonal antibodies and polyreactive immunoglobulins were considered. A new
      interpretation of dose-dependent titration curves was suggested. It was shown
      that our interpretation of dose-dependent titration curves for antibodies which
      are presented in some biological liquids allow obtaining additional information
      about properties of the samples. This information was not obtained earlier
      because of the wrong understanding of the considered problem.

PMID- 22642129
TI  - [Methods used and abandoned in glaucoma].
AB  - The discovery of the disease called glaucoma dates back to the 17th century. Its
      important role as a cause of blindness has been known since the 19th century.
      Initial comprehension of this pathogenesis and treatment belong to the 20th
      century. Its prevention will hopefully be the work of the 21st century.

PMID- 22642130
TI  - Fractal analysis of normal retinal vascular network.
AB  - PURPOSE: In the last decades, various analysis methods with different degrees of
      effectiveness were proposed in medical imaging. Fractal analysis is a
      mathematical technique that can quantify the degree of complexity and optimality
      of vascular networks geometry. The objective of this study is to determine the
      fractal dimension, applying a new standardized protocol for normal vascular
      network of the human retina using fractal analysis. MATERIALS AND METHOD: The
      digitized images of the normal vascular network of the human retina were
      processed and evaluated with the Image J fractal analysis software and the
      fractal dimensions of normal retinal vascular network were calculated using the
      standard box-counting method. RESULTS: The central tendency and dispersion
      measure of fractal dimension were expressed by the mean value and standard
      deviation. The mean fractal dimension of normal arteriovenous retinal vascular
      network was 1.698 +/- 0.003. A comparison with the data from studies performed in
      the ophthalmologic literature was made. CONCLUSIONS: The retinal vascular fractal
      dimension is a noninvasive prediction tool that assist researchers and clinicians
      for early detection of pacients with different retinal vascular diseases.

PMID- 22642131
TI  - [Anti VEGF therapy in different forms of wet ARMD].
AB  - The article presents anti-VEGF therapy in different forms of wet ARMD.

PMID- 22642132
TI  - [Treatment in diabetic maculopathy].

PMID- 22642133
TI  - [Etiopathogenesis in macular edema and therapeutic approach].
AB  - Macular edema is one of the most frequent cause of low vision with very different
      causes. It is a non-specific response to the change in the permeability of blood
      ocular barrier. The tendency of the retina to form cistoid macular edema is
      little understood. There are situations where it is associated with leakage of
      the small perifoveolar capillaries as there are situations, such as diabetic
      macular edema, where the leakage is a diffuse thickening of the posterior pole
      with or without cistoid changes in macula.

PMID- 22642134
TI  - [Panuveitis--difficulties in diagnosis and treatment].
AB  - We report the case of a young patient who had a past history of HSV encefalitis
      and presented for decreased vision in her left eye associated with pain and red
      eye.

PMID- 22642135
TI  - [Myasthenia--ocular type].
AB  - The authors present a case of ocular myastenia, suspected by an ophthalmologist
      and confirmed as diagnosis by a neurologist. There are discussion regarding the
      latest possibilities of treatment.

PMID- 22642136
TI  - [Brown syndrome. General considerations. Case report].
AB  - This is an overview of a few general aspects of Brown's syndrome followed by a
      case report of a three year old girl suffering from congenital Brown's syndrome,
      astigmatism and amblyopia, which was detected by an ophthalmological screening at
      her kindergarten. The main differential diagnosis is ipsilateral inferior oblique
      paresis/paralysis. Since this was a mild-degree syndrome, it didn't require
      surgery only optical treatement and follow-up.

PMID- 22642137
TI  - [Color Doppler imaging and central retinal artery occlusion].
AB  - PURPOSE: To assess the role of CDI of retrobulbar vessels in pathogenic diagnosis
      of CRAO. METHODS: We have used a sonographer with 9 MHz linear probe. RESULTS: We
      present four patients with CRAO that have no emboli visible on ophthalmoscopy The
      first patient had no blood flow signal on CDI on a surface of 2 millimeters
      behind the optic disc. B-scan ultrasound evaluation found a small round, moderate
      reflective echo within the optic nerve, 2 millimeters behind the optic disc.
      Carotid ultrasound examination found an ulcerated ateromatous plaque, as being
      the source of cholesterol emboli. The second patient had no detectable flow in
      central retinal artery due to multiple reverberations determined by calcic
      arterial emboli, placed 5 millimeters behind the optic disc. The chest X-ray
      showed an aortic plaque, considered the source of the emboli. The third patient
      had characteristic CDI findings for Horton disease: low blood velocities and high
      resistance index in all retrobulbar vessels, in both orbits. The diagnosis was
      sustained by carotid ultrasound. The last patient had a very low blood flow
      velocity in CRA, due to acute carotid occlusion. CONCLUSIONS: Ultrasound
      investigation is a valuable diagnostic tool for identifying potential systemic
      conditions associated with CRAO.

PMID- 22642139
TI  - [Rhegmatogenous retinal detachment--clinical case].
AB  - We present the case of a 57 years old woman which was admitted for the amputation
      of the infero-nasal visual field of the right eye, change observed by the pacient
      for 2 weeks. Clinical examination and lab exams revealed the cause of this
      change: a rhegmatogenous retinal detachment in the superior temporal quadrant.
      Surgical treatement was warranted. We did a posterior vitrectomy with trans
      scleral crioapplications and injection of silicone oil 1000. We followed the
      patient's evolution post-operative and we observed the development of a
      complicated cataract which was treated in a second surgery together with the
      extraction of the silicone oil. The evolution was favorable.

PMID- 22642138
TI  - [Leber stellate neuroretinitis: two cases].
AB  - INTRODUCTION: Described by Leber (1916), this clinical syndrome is characterized
      by unilateral decrease of visual acuity, papilledema and macular star. The
      condition concerns the young adult, has a favorable prognosis, and unspecified
      pathogeny. OBSERVATIONS AND METHODS: We report the case of two young adults (25
      and 27 years), examined because of decreased visual acuity in the left eye,
      installed 2-3 weeks after a flu-like syndrome. Ophthalmoscopy reveals papilledema
      and macular star (lipid exudates). Fluorescein Angiography showed abnormal
      permeability at the optic disc, and the absence of vascular changes in the
      macular area. Campimetry, cranio-orbital imaging, and serological tests were
      carried out. RESULTS: Campimetry revealed a centrocecal unilateral scotoma.
      Serological tests for Bartonella hensellae, Lyme disease, leptospirosis, and
      toxacara were negative. The cranio-orbital imaging was normal. Considering the
      syndrome to be idiopathic, no treatments have been performed; the visual acuity
      and papilledema resolved after 4 and respectively 6 weeks, and the macular
      exudates after 8 and respectively 12 months. DISCUSSIONS, CONCLUSIONS: The optic
      disc edema, with or without macular star, unsuitable called Leber's stellate
      neuroretinitis, forms a group of diseases with heterogenous clinical aspect, and
      unspecified pathogenesis. Overall, it is necessary to remember that it is a
      diagnosis of exclusion, targeting infectious pathology in children, and a
      vascular or demyelinating process in adult patients. The favorable prognosis is
      making the cortisone therapy unnecessary in idiopathic forms, but requires a
      specific therapy in infectious forms.

PMID- 22642140
TI  - [Pituitary adenoma--clinical case].
AB  - This is a case report of pituitary adenoma diagnosed by a deep ophthalmological
      examination. We identified a serious neurosurgical and endocrinological
      condition, potentially lethal, starting from an ocular symptom. The patient did
      not pay attention to the hormonal changes as they were developing slowly. Visual
      acuity was the only reason why the patient decided to seek medical attention.

PMID- 22642141
TI  - [Diabetic retrohialoidian hemorrage--invasive minimal treatment].
AB  - Subhyaloid hemorrhage is defined as a localized detachment of vitreous from the
      retina caused by the accumulation of blood, which can lead to sudden and severe
      loss of vision when it takes place in the macular area. The treatment ranges from
      conservative to posterior vitrectomy depending on the cause, age and the status
      of other eye.

PMID- 22642142
TI  - [Intravitreal triamcinolone acetonide treatment in diabetic macular edema].
AB  - PURPOSE: To assess the efficacy and safety of intravitreal triamcinolone
      acetonide in diabetic macular oedema. METHODS: prospective study; 76 patients,
      102 eyes; preoperative assessment: visual acuity, intraocular pressure, fundus
      biomicroscopy fluoresceine angiography, sometimes OCT; postoperative assessment:
      visual acuity, intraocular pressure, fundus biomicroscopy, fluoresceine
      angiography, sometimes OCT. RESULTS: Visual acuity improvement in 42% cases;
      subjective improvement of visual acuity in 72% of cases CONCLUSIONS: Triamcinolon
      acetonide may play a role in treatment of diabetic macular oedema.

PMID- 22642143
TI  - Nanoparticles biodistribution in the eye.
AB  - Nowadays the management of ocular diseases is limited by the inability for
      controlled drug delivery. In the present study micro and nanoparticles based on
      Chitosan labeled with fluorescein, prepared by double crosslinking method in
      water/oil emulsion, were investigated as a new vehicle for intraocular drug
      delivery. The main objective was to study the biodistribution of the prepared
      particles after beind administered into the anterior chamber of pig eyes.
      Nanoparticles were characterized by Scanning Electron Microscopy Laser
      Difractometry and analysis was performed by Confocal Laser Microscopy. The
      designed micro and nanoparticles have average size from 500 nm to 2 microm and
      present round shape, smooth surface, relative high dimensional poly-dispersity
      and relative high porosity. The particles also present good biodistribution at
      corneal, scleral, retinal and optic nerve level after being administered. After
      this eliminary phase we intend to use Chitosan based nanoparticles as a
      controlled drug delivery system for therapies concerning endophthalmitis, age
      related macular degeneration etc.

PMID- 22642144
TI  - [Dinamic visual acuity in presbiastasia patients].
AB  - BACKGROUND: Presbyastasis is a term used to describe the balance deficiences that
      appear in older individuals. One of the main features of presbyastasis is the
      bilateral vestibular hipofunction. The bilateral vestibular hipofunction affects
      the vestibulo-ocular reflex (VOR) leading to oscillopsia. MATERIAL AND METHOD: A
      comparative study between two groups ofpatients: a group of 16 patients diagnosed
      with presbyastasis and a second control group includind 11 healthy subjects. The
      aim of the study was to asses the disturbances of the visual acuity in pacients
      with presbyastasis. The static visual acuity and the dynamic visual acuity were
      measured using a Snellen chart. RESULTS: The dynamic visual acuity was severely
      impaired in patients with presbyastasis in wich the difference between the static
      and the dynamic visual acuity represented more then four lines. CONCLUSION: The
      dynamic vizual acuity can be used in the diagnostic protocol of the balance
      impairments that appear in bilateral vestibulopaties, such as presbyastasis.

PMID- 22642145
TI  - [Comparision of two new optical biometry devices with an ultrasonic immersion
      biometer].
AB  - PURPOSE: To compare two new optical biometry devices with an ultrasonic immersion
      biometer. SETTING: Oftaprof Clinic, Iasi, Romania. METHODS: In this prospective
      comparative observational study were included 420 eyes that underwent cataract
      extraction. Axial length measurements were performed using a Allegro BioGraph
      biometer, which uses optical low-coherence reflectometry (OLCR), an IOLMaster 500
      biometer, which uses partial coherence interferometry (PCI) and an OcuScan
      ultrasonic biometer. The measurement duration and the number of eyes in which the
      measurements with each device could be performed were compared. Intraocular lens
      (IOL) power calculation was performed and the IOL prediction error was calculated
      for each eye four weeks postoperatively. RESULTS: The mean difference in axial
      length measurements was 0.02 mm +/- 0.04 (SD) between the new PCI and the OLCR
      device, 0.14 +/- 0.13 (SD) mm between the ultrasonic biometer and the new PCI
      device and 0.18 +/- 0.09 (SD) mm between the ultrasonic biometer and the OLCR
      device (P=.52, P=.001 and P<.001, respectively). Measurements with the OLCR
      device took significantly longer than with the ultrasonic device (mean difference
      88 +/- 27 seconds), and measurements with the ultrasonic device took
      significantly longer than with the new PCI device (mean difference 188 +/- 46
      seconds) (P<.001). The mean absolute error in IOL power prediction was 0.49 D +/-
      0.29 (SD) with the OLCR device and 0.52 +/- 0.33 (SD) D with the PCI unit and
      0.77 +/- 0.65 (SD) with the ultrasonic biometer. The measurements could be
      performed in 420 eyes (100%) with the ultrasonic biometer, in 152 eyes (36.2%)
      with the OLCR device and in 151 eyes (35,9%) with the new PCI device.
      CONCLUSIONS: Measurements of the axial length were comparable between OLCR device
      and the new PCI device. There was a good correlation between the measurements
      with optical devices and the ultrasonic biometer. Measurements with the OLCR
      device took the longest to perform. Implant power calculation were comparable
      between the two optical devices. The ultrasonic biometry remains a very useful
      tool in cases with severe lens opacification which are extremely frequent in our
      service.

PMID- 22642146
TI  - [Structure-function correlation in early diagnosis of glaucoma progression].
AB  - PURPOSE: The study investigates the correlations between structure and function
      in early detection of glaucoma progression. MATERIALS AND METHOD: A prospective
      study was carried on 204 patients diagnosed with POAG and a follow-up period of 4
      years. All the patients underwent complex ophthalmological examination, C/D
      ratio, Disk Damage Likelyhood Scale (DDLS), automated perimetry and Heidelberg
      retina tomography RESULTS: The relations between structure and function were
      investigated for all patients, but also according to clinical stage of
      glaucomatous damage. Structural progression was more frequently associated with
      perimetric progression for patients with moderate advanced glaucoma. For patients
      with preperimetric glaucoma and early glaucoma, the progression was present more
      often for structural test (19,04% and 29,3%), while perimetric progression was
      less frequent objectivated and weak correlated with structural progression
      (16,66%). For the 15 cases diagosed with both structural and functional
      progression, the locations of the structural lesion and functional defect were
      better correlated in cases involving the poles of the optic disc. CONCLUSIONS:
      Structure-function relation depends on clinical stage of glaucoma and the
      location of the glaucomatous defects. In early stages, structural investigations
      can detect progression before perimetry, while in advanced stages, the functional
      tests are more useful for early detection of progression.

PMID- 22642147
TI  - [The role of OCT in diagnosis and follow-up of diabetic macular ederma].
AB  - PURPOSE: To present the major importance of optical coherence tomography in early
      diagnosis and follow-up of diabetic macular edema. METHOD: The patients diagnosed
      with diabetic retinopathy in our clinic between april 2008 - march 2011 were
      evaluated by OCT and other complementary exams. RESULTS: OCT in diabetic
      maculopathy is useful in the evaluation of the following: presence and area of
      retinal thickening; quantification of retinal thickening; proximity of retinal
      thickening to the centre of the macula; presence or absence of cyst formation
      (cystoid macular edema). CONCLUSIONS: OCT contributes in understanding the
      anatomy of diabetic macular edema and the intraretinal damage and it is the
      technique of choice for the follow-up of diabetic macular edema and for
      monitoring the effect of therapies.

PMID- 22642149
TI  - [Electrochemical sensors based on carbon nanotubes and their use in biomedical
      research].
AB  - Electrochemical sensors based on carbon nanotubes are widely used in biomedical
      studies. According to design the sensors can be divided into three groups: (i)
      sensors based on a carbon nanotube array; (ii) sensors manufactured by means of
      composites containing carbon nanotubes; (iii) sensors, which are electrodes with
      working surface containing carbon nanotubes. The development directions of
      sensors of the first and the second group, and also sensors of the third group
      which are manufactured by abrasive immobilization of carbon nanotubes on an
      electrode surface and by solvent dispersion and casting immobilization of carbon
      nanotubes on an electrode surface by means of N,N-dimethylformamide, surfactants,
      and Nafion are analyzed. The general information on manufacturing techniques of
      these sensors is given. The opportunities of these sensors for biomedical
      researches are demonstrated.

PMID- 22642148
TI  - [One century of the cholesterol model of atherosclerosis].
AB  - 2012 sees the centennial of the development of the cholesterol model of
      atherosclerosis by N.N. Anitchkov and S.S. Khalatov. Its appearance became an
      important stage in the development of atherosclerosis pathogenesis and determined
      the further directions by Anitchkov's investigations direction as well as others
      Russian and world researchers. The Anitchkov biography and the history of
      experimental cholesterol atherosclerosis model creation described in details.
      This article considers the history of the development of the cholesterol model,
      some modern concepts on the nature of hypercholesterolemia (Watanabe's genetic
      model), demonstrating importance of the cell receptors in the homeostasis
      maintenance.

PMID- 22642150
TI  - [Soluble guanylate cyclase in the molecular mechanism underlying the therapeutic
      action of drugs].
AB  - The influence of ambroxol--a mucolytic drug--on the activity of human platelet
      soluble guanylate cyclase and rat lung soluble guanylate cyclase and activation
      of both enzymes by NO-donors (sodium nitroprusside and Sin-1) were investigated.
      Ambroxol in the concentration range from 0.1 to 10 microM had no effect on the
      basal activity of both enzymes. Ambroxol inhibited in a concentration-dependent
      manner the sodium nitroprusside-induced human platelet soluble guanylate cyclase
      and rat lung soluble guanylate cyclase with the IC50 values 3.9 and 2.1 microM,
      respectively. Ambroxol did not influence the stimulation of both enzymes by
      protoporphyrin IX. The influence of artemisinin--an antimalarial drug--on human
      platelet soluble guanylate cyclase activity and the enzyme activation by NO
      donors were investigated. Artemisinin (0.1-100 microM) had no effect on the basal
      activity of the enzyme. Artemisinin inhibited in a concentration-dependent manner
      the sodium nitroprusside-induced activation of human platelet guanylate cyclase
      with an IC50 value 5.6 microM. Artemisinin (10 microM) also inhibited (by 71 +/-
      4.0%) the activation of the enzyme by thiol-dependent NO-donor the derivative of
      furoxan, 3,4-dicyano-1,2,5-oxadiazolo-2-oxide (10 microM), but did not influence
      the stimulation of soluble guanylate cyclase by protoporphyrin IX. It was
      concluded that the sygnalling system NO-soluble guanylate cyclase-cGMP is
      involved in the molecular mechanism of the therapeutic action of ambroxol and
      artemisinin.

PMID- 22642151
TI  - [Thermodynamic analysis of dimerization inhibitors binding to HIV protease
      monomers].
AB  - Here, we describe the analysis of kinetic and thermodynamic parameters for
      binding of peptide and nonpeptide dimerization inhibitors to immobilized HIV
      protease (HIVp) monomers by using surface plasmon resonance. Molecular
      interactions were investigated at different inhibitors concentrations (0-80
      microM) and temperatures (15-35 degrees C). The kinetic, equilibrium and
      thermodynamic parameters have been determined. It was found that both inhibitors
      were characterized by similar interaction parameters. The complex formation is
      entropically driven process for both inhibitors. The entropic term(-TdeltaS) had
      the value about -20 kcal/mol while the enthalpic term (deltaH) had the positive
      value about 14 kcal/mol and counteracted the complex formation.

PMID- 22642152
TI  - [Specificity of molecular recognition in oligomerization of bacterial L
      asparaginases].
AB  - Bacterial L-asparaginases, which are widely used in the antitumor therapy, act
      only as homotetramers, because their active sites are located at the interface
      between the subunits of the enzyme. Since salt bridges substantially stabilize L
      asparaginase tetramers, we have supposed that oligomerization of bacterial L
      asparaginase is a high-avidity process. This assumption was proved by
      bioinformatic and biosensoric methods. It was shown, that a stable tetrameric
      complex can be formed only by the subunits of the same L-asparaginase. Using two
      mutants of L-asparaginase Helicobacter pylori it was shown that specificity of
      molecular recognition is significantly reduced even by single point mutation at
      the interface of high-homologous closely-related subunits.

PMID- 22642153
TI  - [Use of the most recent reagent (CuFL) for stimulation of NO synthesis by the
      medicinal leech salivary cell secretion in the cultures of human endothelium
      cells (HUVEC) and in rat cardiomiocytes].
AB  - The medicinal leech salivary cell secretion (SCS) may stimulate NO-production in
      cultures of human endothelium cells (HUVEC) and rat cardiomiocytes (RCM). This
      effect was detected using a NO specific reagent, - the complex Cu2+ with a
      fluorescein derivative (Cu-Fl). NO had also been detected in the cells by
      fluorescent electronic microscopy and determined quantitatively in the cells and
      in culture fluid by the fluorescence method. SCS stimulated NO synthesis in HUVEC
      cells (but not in RCM) is accompanied by NO release into intercellular space.
      Localization of NO synthesis centers is presented and it is shown that the
      increase in NO levels during the SCS action on HUVEC and RCM is associated with
      the increase in the activity of eNOS/nNOS, but not iNOS. In endothelial cells SCS
      activates nitrosylation processes, assessed by the increase of nitrite-ions in
      the culture medium. It is therefore important to use Cu-Fl, other than Griss
      reagent, during the first hour of analysis of NO synthesis. The NO-depended
      mechanism of SCS action on endothelial cells might be a factor in providing of
      its positive action in hirudotheraphy.

PMID- 22642154
TI  - [A new approach to studying the autoxidation of adrenaline: possibility of the
      determination of superoxide dismutase activity and the antioxidant properties of
      various preparations by polarography].
AB  - The reaction of adrenaline autoxidation in an alkaline buffer with the formation
      of superoxide radicals and the product of its oxidation, adrenochrome, which
      models the quinoid pathway of adrenaline conversion in the body, is accompanied
      by oxygen consumption. This reaction is applicable for polarographic
      determination of the activity of superoxide dismutase and the antioxidant
      properties of biological and chemical compounds, it is based on evaluation of the
      latent period and the rate of oxygen consumption, which are measured in the
      presence of the compounds examined. It was assumed that the neuro- and
      cardiotoxicity of quinone products of adrenaline oxidation is related not only to
      their "own" properties and reactive oxygen species formed but also the hypoxia of
      those regions of the cell and tissue where the quinoid oxidation of adrenaline
      occurs.

PMID- 22642155
TI  - [Determination of phenobarbital in human urine and serum using flow injection
      chemiluminescence].
AB  - A sensitive chemiluminescence method, based on the enhancive effect of
      phenobarbital on the chemiluminescence reaction between luminol and dissolved
      oxygen in a flow injection system, was proposed for the determination of
      phenobarbital. The chemiluminescence intensity responded to the concentration of
      phenobarbital linearly ranging from 0.05 to 10 ng x ml(-1) with the detection
      limit of 0.02 ng x ml(-1) (3 sigma). At a flow rate of 2.0 ml x min(-1), a
      complete determination of phenobarbital, including sampling and washing, could be
      accomplished in 0.5 min, offering the sampling efficiency of 120 h(-1)
      accordingly. The method was applied successfully in an assay of PB for
      pharmaceutical preparations, human urine and serum without any pretreatment with
      recovery from 95.7 to 106.7% and RSDs of less than 3.0%.

PMID- 22642156
TI  - [Erythrocyte lipid composition at different stages of type 1 diabetes in
      children].
AB  - Complete profiles of phospholipid and ceramide molecular species from erythrocyte
      lipid extracts of children without carbohydrate metabolism disorders, and
      children with type 1 diabetes were compared by means of high performance liquid
      chromatography/mass spectrometry. For the first time a statistically significant
      increase (p<0.05) of lysophosphatidylcholine content in two groups of diabetic
      children with different duration of the disease (less than one year and more than
      one year) was found. Statistically significant changes in other lipid classes
      were not observed. The dependence of the content of phosphatidylcholine and
      phosphatidylethanolamine molecular species containing arachidonic acid residue
      (20:4) on the duration of the disease was found. The observed shift in lipid
      metabolism suggests of phospholipase A2 and chronic inflammatory process at
      different stages of diabetes mellitus, in cells (erythrocytes), which aer not
      involved in the immune response.

PMID- 22642157
TI  - [Peculiar properties of glutathione system and NADPH-generated enzymes
      functioning in blood of patients with drug-induced hepatitis under combined
      treatment with epifamin].
AB  - Activity of the glutathione antioxidant system has been studied in patients with
      drug-induced hepatitis treated with standart base therapy and combined with
      epifamin therapy. In blood serum of patients before treatment the decrease of
      reduced glutathione (GSH) level and the increase of glutathione peroxidase (GP)
      and glutathione reductase (GR) activities versus control were observed. Combined
      treatment with epifamin changed GSH level to the normal values. Treatment with
      epifamin was accompanied by pronounced increase in GP and GR activities compared
      with standard therapy. Activities of the NADPH-generated enzymes, glucose-6
      phosphate dehydrogenase and NADP-isocitrate dehydrogenase, which decreased at
      this pathology, also demonstrated a more significant increase than standart
      treatment.

PMID- 22642158
TI  - [Effective photosensibilizator selection for E.N.T.-organ diseases treatment,
      based on their accumulation in pathologically changed tissues].
AB  - Accumulation of photosensibilisators - derivatives of E6 chlorines
      ("Radachlorine", "Photoditazine", "Zelevsky's balsam") in the mucous membrane and
      selection of most effective sources of emission have been investigated in 30
      patients with rhinosinusitis and 10 with tonsillitis. As a source of emission we
      used light emitting diode (LED) matrix device "ACT" (wavelength approximately 405
      nm (Sore band)) and a laser device LAHTA-"MILON"-ML500-SP (wavelength 662 nm).
      Drug accumulation in the mucous membrane and changes of their concentrations
      after emission were evaluated by changes of fluorescence, measured with a LESA-01
      BIOSPEC spectrometer. The percent of fluorescence decrease ranged from 50% to
      92.7%. This suggests intensive disintegration of photosensibilisators, and
      consequently, high therapeutic activity of this method. Effectiveness of this
      method is also confirmed by clinical results.

PMID- 22642159
TI  - [In to the question of selenium using in case of foodstuffs enrichment].
AB  - The analysis of different selenium compounds toxicity and level of selenium
      intake in different countries are given in the article. It showed that population
      of Russian Federation have not defined selenodeficiency. Thus there is no need in
      wide-ranging fortification of foodstuff by selenium. For increasing of selenium
      level in particularized foodstuffs (biology activity supplements, specialized
      foodstuff for pregnant, children, dietetic, medicinal and prophylactic foodstuff)
      are preferred the organic forms of selenium. Inorganic forms of selenium
      (selenites and selenates) could use only in the composition of biology activity
      supplements. However in this case the organic form is more preferably too.

PMID- 22642160
TI  - [Characteristics of collagen's material bifidogenic properties].
AB  - It is still essential to search for new, available food ingredients with
      bifidogenic effect, to study their safety, efficacy and production effectiveness
      upon the creation of functional foods. The review considers protein products such
      as collagens and their hydrolyzates, which are used in culture mediums as growth
      factor. They are treated, besides carbohydrate prebiotics, as potential
      bifidogenic nutrients. Collagen hydralyzates contain all amino acids, required
      for bifidobacteria growth. That is why it is considered essential to provide
      control over its biosafety. However, recyclable materials of animal origin are
      included into a list of Specific Risk Materials of prion disease agents
      transmitting. Collagen hydralyzates are preserved up to distal intestine parts.
      This fact approximates their qualities to oligosaccharids' type of prebiotic food
      fibers, related to the lack of absorption and hydrolytic stability. The
      additional study of mechanisms of bifidobacteria's forcing is required. It can be
      made at the expense of the modification of the albuminous cell metabolism during
      the collagen hydralyzats' unilization.

PMID- 22642161
TI  - [Effects of dietary fat level on the xenobiotic metabolism enzymes activity and
      antioxidant enzymes in rats].
AB  - Male Wistar rats received fat-free diet or diets containing 5, 10 and 30% of fat
      (sunflower oil + lard, 1:1) for 4 weeks. The direct relationship between dietary
      fat level and ethoxyresorufin O-dealkylase activity of CYP1A1, methoxyresorufin O
      dealkylase activity of CYP1A2, pentoxyresorufin O-dealkylase activity of CYP2B1
      and testosterone 6beta-hydroxylase activity of CYP3A was found. Activities of key
      enzymes of phase II xenobiotic metabolism (total activity of glutathione
      transferase, activity of UDP-glucuronosyle transferase) and antioxidant enzymes
      (catalase, glutathione peroxidase, glutathione reductase, paraoxonase-1 and heme
      oxygenase-1) also increased with higher dietary fat level.

PMID- 22642162
TI  - [Postprandial dynamics of the content of hydrolytic enzymes of blood in men with
      different levels and specificity of daily muscle loading].
AB  - In a cohort of healthy young men with different levels of physical activity the
      content of hydrolytic enzymes (ELISA) in serum was studied. In the conditions of
      relative physiological rest in sportsmen (fighters and skiers) were defined
      differently directed changes of the level of hydrolytic enzymes during the
      various periods after a breakfast. Changes associated with a sports orientation
      and level of daily physical activity were revealed.

PMID- 22642163
TI  - [The separate and combined effects of calcium pantothenate deficiency and cadmium
      intoxication on rat reproductive function].
AB  - The publication presents investigation evaluated of separate and combined effects
      of calcium pantothenate deficiency and cadmium (Cd2+) intoxication on rat
      reproductive function. The experi-ments were performed on 280 adult and 890
      offspring of Wistar rats. Reproductive function was estimated by fertility study,
      prenatal and postnatal development of offspring. The separate and combined
      effects of and cadmium intoxication during the mating period and pregnancy had no
      effect on fertility and fecundity of rats, pre-and postimplantation loss, the
      survival of offspring, and not caused the abnormal development of skeleton and
      internal organs. However, in prenatal ontogeny of this effect was manifested by
      lower body weight and fetal growth, postnatal - underdevelopment of rat pups in
      all morphological and functional studied parameters and increasing number of
      stillbirths in the offspring.

PMID- 22642164
TI  - [Detection of recombinant-DNA in foods from stacked genetically modified plants].
AB  - A quantitative real-time multiplex polymerase chain reaction method was applied
      to the detection and quantification of MON863 and MON810 in stacked genetically
      modified maize MON 810xMON 863. The limit of detection was approximately 0,1%.
      The accuracy of the quantification, measured as bias from the accepted value and
      the relative repeatability standard deviation, which measures the intra
      laboratory variability, were within 25% at each GM-level. A method verification
      has demonstrated that the MON 863 and the MON810 methods can be equally applied
      in quantification of the respective events in stacked MON810xMON 863.

PMID- 22642165
TI  - [About the regulation of ionizing radiation using for food treatment in the
      international legislation].
AB  - The international and European legislation in the field of ionizing irradiation
      (gamma rays, electrons or X-rays) using for food treatment for improving food
      safety, for disinfestation of plants or plant products and improving of
      technological characteristics of food are discussed in this article. Obtained
      data can be used for foundation of Russian legislation and normative documents in
      the field of radiation methods using in the food industry.

PMID- 22642166
TI  - [Features of feeding behavior of students of the Peoples' Friendship University
      of Russia].
AB  - The feeding behavior of students of Peoples Friendship University of Russia from
      55 countries (557 persons) was studied by questionary method. Most students (83%)
      recognized the changes in nutrition after admission to the university. A quarter
      of students noted the ill health. The adaptation to the new nutrition type of at
      12% per a year of study. About third (31%) rated their nutrition as good, 39%--as
      satisfactory, 20%--unsatisfactory at the moment of research. 80% of students
      broke a diet. About half of students (51%) regularly miss a breakfast, 34% and
      15%--miss a dinner and supper. More than 60% of students eat hot meals not
      oftener than once a day. Insufficient consumption of fish, eggs and bean by
      students also was noted in the course of research. Irrationality of the
      educational schedule and the high prices for foodstuffs are leading causes of
      breaking of nutrition according to students.

PMID- 22642167
TI  - [Enriched and functional foodstuffs: similarities and differences].
AB  - A comparison of fortified and functional foods on such parameters as destination,
      food group, the principles of enrichment with vitamins and/or macro- and
      micronutrients, doses and forms of vitamins and minerals, hygienic regulations of
      micronutrients usage and content in the final product, regulatory and technical
      documentation, duration of application, effectiveness, labeling, information for
      consumers has been carried out. Insufficiency and the need to improve the
      regulatory framework for functional foods are noted.

PMID- 22642168
TI  - [Functional performance of the cardiovascular system in patients with overweight
      and obesity].
AB  - Was investigated 471 patients with obesity and cardiovascular diseases. Direct
      dependence between degree of expressiveness of obesity and the clinical status,
      severity of infringement of a functional condition of cardiovascular system,
      frequency of development of complications is revealed.

PMID- 22642169
TI  - [Features of hormone metabolism in reproductive age women with metabolic
      syndrome].
AB  - Aim of this study was the investigation of feature of hormonal status in patients
      with metabolic syndrome (MetS). 111 reproductive age women were included in the
      study. According to diagnostic criteria for MetS of Society of Cardiology of the
      Russian Federation (2009) they were divided into two groups--study group (n=52)
      and control group (n=59). It was studied composition of body (fat mass, skeletal
      mass, lean mass, total, intracellular and extracellular fluid), parameter of
      lipid and carbohydrate metabolism, parameter of hormonal status. Study of
      hormonal status in reproductive age women with MetS showed a higher level of
      fasting and postprandial levels of insulin and C-peptide, hyperleptinemia and a
      reduced level of sex hormone-binding globulinn (SHBG). We suggest that serum
      leptin and SHBG levels may be used as an additional diagnostic criteria in these
      patients.

PMID- 22642170
TI  - [Influence of a low-calorie diet with inclusion of probiotic product containing
      bacterias Lactobacillus plantarum Tensia DSM 21380 on clinical and metabolic
      characteristics in patients with obesity and arterial hypertension].
AB  - In a number of studies it is shown that regular use of the probiotic products
      containing Lactobacillus plantarum Tensia DSM 21380 in complex dietary treatment,
      not only modulates intestinal microflora, but also has a positive influence on a
      functional condition of cardiovascular system including levelels of systolic and
      diastolic blood pressure. The aim of this research was to study the influence of
      dietotherapy with inclusion of the probiotic product containing Lactobacillus
      plantarum Tensia DSM 21380, on clinical and metabolic characteristics in patients
      with obesity and accompanying arterial hypertension (AH).

PMID- 22642171
TI  - [Morphometry characteristic of the gut mucous membranes condition in growing rats
      with different selenium provision].
AB  - The purpose of the given work was to research an influence of polysynthetic diet
      with various levels of selenium on a condition of distal small intestine mucous
      membranes in rats. Mucous membranes of distal small intestine were studied by
      common morphological and morphometrical methods. The histological estimation of
      influence of quantity of consumed selenium has shown that adverse changes in a
      mucous membrane of intestines of the rats receiving low selenium diet are most
      expressed, and least--at the animals receiving a diet as much as possible
      enriched organic form of selenium.

PMID- 22642172
TI  - [Cardioneurology: the up-to-date key positions and the future prospects].
AB  - The up-to-date key positions and the future prospects of cardioneurology were
      analyzed. The wide range of questions of cardioneurology was represented and the
      necessity of the interdisciplinary approach to the diagnostics, treating and
      prevention of the cerebrovascular diseases were proved. It was pointed that the
      studied problems are the priority directions in angioneurology and have great
      social and clinical importance.

PMID- 22642173
TI  - [The assessment of reactions of polygraphic parameters at HRV-biofeedback
      training in adolescents with different variants of cardiac autonomic nervous
      system tone].
AB  - There is examine a character of change of brain bioelectric activity and
      polygraphic indicators at sessions of biofeedback by heart rhythm variability
      parameters (HRV-biofeedback) in 15-17 years adolescents who have different
      variants of cardiac autonomic nervous system tone. It is taped, that adolescents
      with cardiac balanced tone have more intensive optimization of functional brain
      activity in comparison with adolescents who have cardiac sympathetic tone -
      increase on alpha-activity and theta-activity depression in electroencephalogram
      structure. There were optimization of neurodynamic processes and most expressed
      stabilization of the hemodynamics indicators in adolescents with cardiac
      sympathetic tone after HRV-biofeedback training.

PMID- 22642174
TI  - [Estrogen receptors beta--new target in cellular lung cancer treatment].
AB  - Literature review upon various types of estrogen receptors expression (type alpha
      and beta) in the cells of cellular lung cancer, their participation in estrogen
      and antiestrogen effects implementation, influence of estrogens and antiestrogens
      on occurrence and progression of malignant lung tumors in animals and humans.
      Were analyzed reasons of data ambiguity on type beta estrogen receptors (ERbeta)
      expression frequency. The results of authors own research in quantitative
      assessment of ERbeta expression in tumor tissue of patients with cellular lung
      cancer (79 male and 22 female patients are presented in this article. An increase
      in expression rate and incidence of tumors with high ERbeta level has been shown
      in patients with lung adenocarcinoma regardless of smoking status or gender. A
      new strategy of antiestrogen use, especially tamoxifen, has been formulated for
      cellular lung cancer treatment. Authors believe in a positive effect of adjuvant
      treatment with tamoxifen in patients with ERbeta-positive cellular lung cancer
      used independently or during and after the chemotherapy, by analogy with breast
      cancer patients.

PMID- 22642175
TI  - [VEGF in neoplastic angiogenesis].
AB  - Solid tumor progression largely depends on vascularization and angiogenesis in
      the malignant tissue. The most prominent among all proangiogenic factors is
      vascular endothelium growth factor (VEGF). VEGF suppression leads to
      retrogression of neoplastic vessels and tumor growth restriction. Clinical trials
      of complex antiangiogenic and chemical therapy of different neoplastic tumors
      have shown promising results. Nowadays bevacizumab is widely used in breast
      cancer, colorectal cancer and II-IV stage of malignancy gliomas treatment.
      Unfortunately, in the majority of cases antiangiogenic treatment led not to full
      recovery, but only to tumor development restriction. Resistance mechanisms
      include potentiating of alternative proangiogenic signaling pathways and
      activation of malignant cell invasive population.

PMID- 22642176
TI  - [Comparison of different methods of molecular-genetic analysis of somatic
      mutations in K-ras gene in patients with colorectal cancer].
AB  - Two approaches to somatic point mutations in 12 and 13 codones of K-ras gene were
      analyzed: PCR/SSCP/ACRS/sequencing and allele-specific PCR in the real-life
      regimen (Russian set "KRAS-7M"). The comparison was carried out on 62 examples of
      genomic DNA extracted from frozen colon carcinomas, which underwent manual
      dissection. The results obtained in two attempts were consistent in 95,2% (N=59).
      Specificity and sensitivity of K-ras mutations detection using "KRAS-7M" set were
      100 and 96,4% respectively, and 94,1 and 100% respectievly using
      PCR/SSCP/ACRS/automatic sequencing. False positive results were absent when
      detecting with "KRAS-7M" and accounted for 2 cases (5,9%) when using PCR/SSCP/
      ACRS/automatic sequencing. The only false negative response (3,6%) was obtained
      analyzing mutations using "KRAS-7M".

PMID- 22642177
TI  - [Oncolytic parvoviruses. A new approaches for cancer therapy].
AB  - Parvoviruses such as parvovirus H-1 (H-1PV) may selectively infect and lysis
      cancer cells. The parvoviruses also induce an immune system to eliminate the
      tumor cells through the formation of anti-cancer immunity. One of the possible
      mechanisms of antitumor activity is associated with the direct induction of
      apoptosis by parvoviral proteins NS1 and 11 kDa. Parvovirus-based vectors are
      promising for gene therapy of oncological diseases and genetic disorders in
      humans. Parvoviruses were successfully used for the experimental treatment on
      animal models of human glioma, neuroblastomas, lymphomas, pancreatic carcinoma,
      carcinomas and breast tumors. ParvOryx is the first oncolytic preparation
      constructed on the base of H-1PV; its phase I/IIa clinical trials in patients
      with glioblastoma multiforme are in process.

PMID- 22642178
TI  - [Estrogens and brain].
AB  - Recent data upon molecular mechanisms of pleiotropic action of estrogens in human
      brain is presented in the article. Given detailed descriptions of properties of
      classical and membrane bound estradiol receptors, that maintain gene expression
      regulation, modulation of neurotransmittent systems and signal cascade activation
      in neuronal cells. Data upon regional distribution of estradiol receptor subtypes
      in the brain, their participation in main cell population function control
      (including progenitor cells) is given. Special attention is paid to estrogen
      participation in neurogenesis, inflammation and apoptosis regulation in central
      nervous system; in the control of formation and functioning of cerebral vessels.

PMID- 22642179
TI  - [Clinical significance of insulin resistance syndrome in development of
      endothelial dysfunction in patients with primary gout].
AB  - Endothelial function has been studied in 175 males with primary gout. It has been
      established that incidence of endothelial dysfunction in patients with primary
      gout was associated with the clinical course and was marked most of all in
      patients who had a chronic gout. The correlations found between the parameters of
      endothelial dysfunction and impaired carbohydrate metabolism suggest close link
      and coordination between the above processes which contribute greatly to
      development and progress of atherosclerosis in such patients.

PMID- 22642180
TI  - [Outbreak of acute enterovirus intestinal infection in Sakhalin region in August
      2010].
AB  - The investigation of cases of acute intestinal infections in the Sakhalin region
      of Russia in August, 2010 is described. Epidemiological and molecular biological
      studies were conducted. After initial PCR screening and determining the
      nucleotide sequences of the positive samples the following enteroviruses were
      found: Coxsackie A2 - 42 samples (45%), Coxsackie A4--31 sample (34%),
      Enterovirus 71--6 samples (6,5%), Coxsackievirus B5--6 samples (6,5%), Coxsackie
      B3--4 samples (4%) and Coxsackie B1--4 samples (4%). The phylogenetic analysis of
      sequences showed that the closest analogues for the nucleotide sequences of these
      genotypes were previously identified in Japan, Korea and China in 2000-2010.

PMID- 22642181
TI  - [Proteomic profile and non-specific immunoprophylaxis of respiratory diseases in
      frequently sick children].
AB  - We have investigated efficacy of meglumine acridonacetate (Cycloferon)
      infrequently sick children (FSC) on the basis of serum proteomic profile
      dynamics; we have also studied epidemiologic efficacy of interferon inductor as a
      mean of non-specific immunoprophylaxis. FSC were subjects to follow up during 4
      10 years. We have used recommended regimens of drug administration. Were
      analyzed: anamneses of FSC, clinical symptoms, infectious index calculation,
      stratification of children into 5 groups of FSC and separation of children with
      truly frequent recurrent respiratory viral diseases. On the basis of proteomic
      blood analyzes the following parameters of efficacy of treatment with meglumine
      acridonacetate were defined: expression intensity of Rho- and Ras-signaling
      pathways proteins. Epidemiologic efficacy of the drug was 2,9 (from 2,4 to 3,4),
      rate of protection--62,8% (58,5-67,1%).

PMID- 22642182
TI  - [Effectiveness of an occupational therapy program for health promotion among
      healthy elderly. A randomized controlled trial].
AB  - OBJECTIVES: The purpose of this study was to evaluate the effectiveness of an
      occupational therapy program for health promotion among healthy elderly by a
      randomized controlled trial. METHODS: Participants were 220 community-dwelling
      healthy elderly, 65 years of age or older. They were assigned randomly to: an
      experimental group receiving a 15-session MOHO program consisting of lectures and
      seminars about personal causation, values, interests, roles, habits, motor
      skills, process skills, communication and interaction skills, and environment; a
      control group which received a 15-session crafts program or no treatment. Quality
      of life was compared between groups using the MOS 36-Item Short-Form Health
      Survey (SF-36), WHO/QOL-26 (QOL26) and Life Satisfaction Index Z. The Fisher's
      exact test and the t-test were used to assess differences between the two groups.
      RESULTS: The follow-up rates for the experimental and control groups were 71% and
      72%. The experimental group comprised 80 people (mean age +/- SD, 71.1 +/- 4.68
      years) and the control group 79 (71.4 +/- 4.66 years). Mean change of the
      following items for the experimental group was significantly greater from that of
      the control group: a BP of SF-36 (P = 0.05); and an environment score of QOL26 (P
      = 0.02). CONCLUSION: The findings provide evidence that the MOHO program can meet
      coping and influence needs, thus improving QOL. We further conclude that the MOHO
      program is an effective interventional method for improvement of literacy about
      health and occupation.

PMID- 22642183
TI  - [Perceived stress and cardiovascular disease mortality. The Ohsaki Cohort Study].
AB  - OBJECTIVES: Previous studies have indicated that stress can affect the
      circulatory system. Although prospective studies have examined the association
      between perceived stress and cardiovascular disease (CVD) mortality, the results
      are still controversial. The purpose of the present study was to elucidate the
      relationship with stratified analyses by alcohol intake category and smoking
      status. METHODS: The prospective Ohsaki Cohort Study covered all National Health
      Insurance beneficiaries aged 40 to 79 years living in the precinct of Ohsaki
      Public Health Center, Miyagi, Japan. A total of 45,293 Japanese (21,552 men and
      23,741 women), without a history of cancer, ischemic heart disease or stroke, and
      who answered all items related to stress level at the baseline in 1994, were
      followed prospectively. Over 12 years of follow-up, 1,751 deaths from CVD
      occurred (994 men and 757 women). We used Cox proportional hazards models to
      calculate the hazard ratios (HR) and 95% confidence intervals (CI) for CVD
      mortality according to the perceived stress categories. The low stress category
      was used as the reference in all analyses. RESULTS: Perceived stress demonstrated
      a significant positive association with CVD mortality for men; the multivariate
      adjusted HR for high versus low stress was 1.43 (95% CI: 1.19, 1.87, P = 0.006).
      No significant relationship was noted for women. With current smokers, perceived
      high stress versus low had a pronounced association for both men (HR = 1.76, 95%
      CI: 1.28, 2.41, P = 0.001) and women (HR = 1.61, 95% CI: 1.20, 2.16, P = 0.004),
      and a similar tendency was noted for current drinking (HR = 1.56, 95% CI: 1.16,
      2.09, P = 0.006, HR = 1.42, 95% CI: 1.08, 1.87, P = 0.001). Additionally, for
      both smoking and drinking men, those reporting high stress had 2 times the risk
      of CVD mortality of their low stress counterparts (P for trend < 0.001). The
      interaction of perceived stress with smoking for CVD mortality was of borderline
      statistical significance only for men (P for interaction = 0.04). CONCLUSION: The
      results suggest that the percentage of current smoking and drinking are factors
      that distinguish between sexes with regard to the effects of perceived stress on
      the incidence of CVD mortality. Furthermore our present findings indicate that
      smoking and drinking habit are not the way to relieve one's stress. A review of
      these should be conducted and we need to enhance support for stress management as
      well as control over smoking and drinking habits.

PMID- 22642184
TI  - [Study on difficulties and solutions of activities according to dispatch type of
      dietitians in Japan Overseas Cooperation Volunteers].
AB  - OBJECTIVE: The objective of the study was to identify differences in the content
      and difficulty of activities according to dispatch type (new volunteer or
      successor) of dietitian Japan Overseas Cooperation Volunteers (JOCV) and to
      analyze their support needs. METHODS: A questionnaire was distributed concerning
      the dispatch type, the activities' contents, and the difficulties of all ex-JOCV
      dietitians in 2007. A total of 66 members provided responses. RESULTS: Activities
      involving nutrition education for community residents were greater among new
      volunteers compared to successors, whereas the management of clinical nutrition
      in hospitals was greater in the successors. The difficulties of both types of
      volunteers were related to acquiring their positions, coordinating activities,
      and offering services based on the values and lifestyles of the peoples. The rate
      for volunteers with local counterparts was significantly smaller among new
      volunteers. Both types refered to advice in books to overcome their difficulties.
      It will be necessary to develop effective books to support JOCV dietitians.
      CONCLUSION: The study identified differences in the content and the difficulty of
      activities according to the volunteer dispatch type and provided information on
      support needs for dietitians in the JOCV.

PMID- 22642185
TI  - [Descriptive epidemiology for two outbreak cases of norovirus gastroenteritis in
      an elementary school].
AB  - OBJECTIVES: Although noroviruses (NV) sometimes cause large outbreaks of
      gastroenteritis, the source of infection is often unclear. However, evidence of
      environmental contamination has been reported. We have encountered two norovirus
      outbreaks suggesting the environmental contamination was the source. This study
      presents results for descriptive epidemiology of these two outbreaks. METHODS:
      Two outbreaks of norovirus gastroenteritis occurred in March and December 2009 at
      the same elementary school. In the first outbreak, whether the school children or
      the teaching staff had consumed school lunch and whether they had entered the mid
      area of the second floor in the S school building were studied as risk factors.
      In the second outbreak, the focus was on whether they had entered the second or
      third floors in the T school building. We compared the cumulative attack rates
      with and without these risk factors. To detect the norovirus gene, real-time
      polymerase chain reactions were performed with stool specimens. When NV-positive,
      sequence analyses, homology tests and phylogenetical analyses were further
      conducted. RESULTS: The norovirus genotype GII/9 was detected from stool
      specimens of the patients in the first outbreak, and genotype GI/4 in the second
      outbreak. Homology testing showed the tested viral genes to have 100% identity in
      each outbreak. In the first, gastroenteritis cases were concentrated in the
      school children who entered the mid area of the second floor in the S school
      building regardless of their consumption of school lunch, though the cumulative
      attack rate in the class that consumed the school lunch was higher than that in
      the class that did not. In the second outbreak, the patients were concentrated
      partly on the third, and particularly, on the second floor in the T school
      building, despite the fact that all the children shared the same lunch menus.
      CONCLUSION: The two outbreaks occurred independently with different genotypes.
      The distribution of the gastroenteritis cases in the school buildings suggests
      environmental contamination as an infection source of norovirus in the background
      of these two outbreaks. Furthermore, the spatial and temporal patterns of the
      gastroenteritis cases suggest that there might have been multiple sources on the
      different floors in the second outbreak. These results indicate that
      understanding widespread environmental contamination of norovirus is critical to
      prevention of further outbreak of norovirus gastroenteritis.

PMID- 22642186
TI  - [Relationship of childhood eating habits with unbalanced diets among mothers of
      infants].
AB  - OBJECTIVES: The purpose of this study was to determine the relationship between
      mothers with infants behavior of eating/not eating disliked foods and food intake
      with education regarding eating habits in childhood. METHODS: The cross-sectional
      study was conducted with 1145 mothers at 15 public kindergartens in A-prefecture
      B-city. Attributes of each mother's behavior regarding eating disliked foods,
      their number, frequency of food intake, eating breakfast and supper together and
      education regarding eating habits in childhood were evaluated using a
      questionnaire. RESULTS: The 'eat/probably eat disliked foods' group showed a
      lower number of disliked foods, a higher food intake frequency score and a higher
      ratio for receiving eating habit education in childhood with regard to helping
      with meal making, eating the meal dished up by one person, not watching
      television while eating meals, eating meals with seasoning and cut small for
      children. In this study, execution rates for these eating habit education items
      were subordinate. CONCLUSION: These results suggest that eating disliked foods
      relates to food intake balance and receiving eating habit education in childhood
      in an environment in which children can concentrates easily on their meals.
      Therefore, it is suggested that promoting these education items is a high
      priority.

PMID- 22642187
TI  - Matrix metalloproteinase inhibitors: specificity of binding and structure
      activity relationships.

PMID- 22642188
TI  - Matrix metalloproteinases.
AB  - Remodeling of extracellular matrix is crucial for many physiological (cell
      migration, proliferation, growth, and development) and pathological (remodeling
      of heart, carcinogenesis, metastasis, etc.) events. Thus, the interaction between
      cells and extracellular matrix plays a key role in normal development and
      differentiation of organism and many pathological states as well. Changes in
      extracellular matrix are regulated by a system of proteolytic enzymes that are
      responsible for proteolysis of huge quantity of extracellular matrix components.
      Matrix metalloproteinases (MMPs) represent the main group of regulating proteases
      in ECM. Ability of matrix metalloproteinases to modify the structural integrity
      of tissues is essential for certain aspects of normal physiology and pathology.
      The ability to process molecules such as growth factors, receptors, adhesion
      molecules, other proteinases, and proteinase inhibitors makes MMPs potent
      controllers of physiological and pathological events in the cell
      microenvironment. Overactivation of MMPs has been implicated in numerous disease
      states.

PMID- 22642189
TI  - Specificity of binding with matrix metalloproteinases.
AB  - Matrix metalloproteinases (MMPs) regulate a wide range of biological functions;
      hence, they have invited great attention for the studies on their structures and
      functions, and since their overactivation leads to several diseases, the design
      and discovery of their potent inhibitors have become the need of the day. Since
      there have been so far discovered 28 different types of human MMPs, the
      specificity of binding of inhibitors with each different MMP needs special
      attention. The chapter presents the X-ray crystallographic and NMR studies on
      three-dimensional structures of a number of MMPs to reveal their catalytic site,
      subsites, specificity of binding with substrate and inhibitors, and catalytic
      mechanism. In addition to catalytic site, MMPs possess some subsites designated
      by unprimed and primed S, e.g., S1, S2, S3 and S1', S2', S3'. Among these, the
      S1' pocket varies the most among the different MMPs varying in both the amino
      acid makeup and depth of the pocket (shallow, intermediate, and deep pocket
      MMPs). This, along with the flexibility in the structures of MMPs, could be of
      great help in the design and the development of selective MMP inhibitors (MMPIs).
      The determination of affinity of inhibitors and the cleavage position of peptide
      substrates is mainly based on P1'-S1' interaction (P1', the group in inhibitor or
      substrate binding to S1' pocket of the enzyme), and it is the main determinant
      for the affinity of inhibitors and the cleavage position of peptide substrates.

PMID- 22642190
TI  - The gelatinases and their inhibitors: the structure-activity relationships.
AB  - The interest in gelatinases is increased because of their association in diverse
      human diseases, though the relationship between MMP expression and disease
      progression is very complex and varies in cell to cell. Targeting gelatinases in
      disease treatment is complicated by the fact that gelatinases are indispensable
      for normal development and physiology due to their multifunctionality, possible
      functional redundancy, context-dependent expression, and activity. They are
      secreted as inactive zymogens which are processed to become active by removal of
      N-terminal propeptide. The folded conformation of zymogen is required to keep the
      gelatinases in its latency. Acting on a broad spectrum of extracellular
      substrates, the gelatinases (both MMP-2 and MMP-9) are critical to the biological
      processes. Three-dimensional structures of gelatinase-inhibitor complexes and
      inhibition profiles of compounds screened on them provide an invaluable source to
      gain insight into the structural determinants as well as functional selectivity.
      The quest for selective MMP inhibitors (MMPIs) still remains a challenge in
      search of successful clinical candidates. An increased understanding of the
      structure, regulation, and function of the individual MMPs will likely lead to
      more effective strategies in the development of highly selective inhibitors for
      any given MMP that can then be exploited to achieve the desired drugs.

PMID- 22642191
TI  - Advances in studies on collagenase inhibitors.
AB  - Matrix metalloproteinases (MMPs) play an important role in many physiological and
      pathological processes. Development of MMP inhibitors, in particular collagenase
      inhibitors, for the treatment of arthritis has been more challenging,
      undoubtedly. Small-molecular-weight collagenase inhibitors may be classified into
      several different arbitrary structural classes, depending on the catalytic zinc
      binding function as well as other structural elements of the inhibitors. This
      chapter tries to make an attempt in providing the reader with an overall flavor
      of the type of scaffolds reported in the past few years along with the molecular
      modeling studies.

PMID- 22642192
TI  - Hydroxamic acids as matrix metalloproteinase inhibitors.
AB  - Matrix metalloproteinases (MMPs), an increasing family of zinc- and calcium
      dependent endopeptidases, are involved in both the tissue remodeling and the
      degradation of extracellular matrix (ECM). These enzymes have been a
      pharmaceutical target for over 25 years in order to develop many families of
      therapeutically important synthetic matrix metalloproteinase inhibitors (MMPIs)
      for the treatment of several serious pathologies. Although clinical trials on
      most of the MMPIs gave disappointing results, at least one MMPI (Periostat) has
      been approved by the FDA for the treatment of periodontal disease. Current
      research efforts on the development of selective inhibitors toward certain MMPs
      gave a vast number of small molecules as potent MMPIs, of which, some of the
      effective candidates are in their various stages of (pre)clinical trials for the
      treatment of various diseases such as arthritis and different cancers. The
      selectivity of MMPIs toward specific MMPs depends mainly on their structural
      templates or scaffolds and the variations in their substituents. Thus, the
      combination of traditional, mechanism-based, and structural-based approaches may
      help for the future development of specific MMPIs. In recent years, research
      focuses on the design and development of MMPIs possess a hydroxamic acid moiety,
      a strong Zn(II)-binding group, which leads to their high-affinity binding to the
      enzymic sites of the MMPs. We herein discuss the hydroxamic acid-based MMPIs with
      respect to their mechanism of interaction, structure-activity relationship (SAR),
      quantitative structure-activity relationship (QSAR), recent development, and
      clinical trials.

PMID- 22642193
TI  - Quantitative structure-activity relationship studies on sulfonamide-based MMP
      inhibitors.
AB  - Matrix metalloproteinases (MMPs) regulate a wide range of biological functions,
      but their overactivation leads to a wide array of disease processes such as
      rheumatoid arthritis, ostereoarthritis, tumor metastatis, multiple sclerosis,
      congestive heart failure, and a host of others. Therefore, the study of MMP
      inhibitors has evoked a great interest among scientists. As a result, different
      groups of compounds have been synthesized and studied for MMP inhibitions. Among
      them, a large number of structurally novel sulfonamide derivatives have been
      reported to be potential MMP inhibitors, but only a few have reached to the final
      stage of clinical trial. Many authors have made quantitative structure-activity
      relationship (QSAR) studies on them to provide the guidelines to design more
      potent MMP inhibitors. This article presents a comprehensive review on all such
      QSARs reported with critical assessment in order to provide a deeper insight into
      the structure-activity relationship of sulfonamides which can be used to
      synthesize highly potential drugs of pharmaceutical importance.

PMID- 22642195
TI  - [Presentations on exciting topics].

PMID- 22642196
TI  - [Acknowledging the work of nurses].

PMID- 22642197
TI  - [Implementing necessary reforms].

PMID- 22642198
TI  - [Making the perceived accessible].

PMID- 22642199
TI  - [Being a nursing home resident--a challenge for one's identity].
AB  - When entering the nursing home, elderly people are afraid of losing their
      independence and identity. That is why the entry into a nursing home turns out be
      a critical experience for the people affected. A systematic literature research
      on this topic illustrates that the impacts of a nursing home entry on the
      identity of these people have only scarcely been investigated so far. In the
      present study, 20 problem-centred interviews with residents of three different
      nursing homes were conducted and analysed according to the summarizing content
      analysis developed by Mayring (2007). The result shows that moving into a nursing
      home is accompanied by a strong emotional burden as these people have to leave
      behind their friends, families, pets, long-time neighbours and property.
      Moreover, other residents of the nursing home create fear through their need of
      care. The test persons participating in the present study do not want to have
      their decisions and actions imposed from outside because of their need of nursing
      care. They protest against it. They draw enough strength from the social network
      they maintain, from conversations and from their faith in order to fight for
      their independence. They develop a new identity close to their former identity by
      maintaining autonomy and mobility, and they stay future-oriented.

PMID- 22642200
TI  - [Effectiveness of a case management program for the elderly in early stage
      dementia and their caregivers].

PMID- 22642201
TI  - [Buffer between personnel and home management (interview by Sylke Werner)].

PMID- 22642202
TI  - [Keeping the goal in sight].

PMID- 22642203
TI  - [Exposing occupational stress].

PMID- 22642204
TI  - [Reframing producing "more"].

PMID- 22642205
TI  - [Forming substantiated decisions].

PMID- 22642206
TI  - [The initiative of the employee is required].

PMID- 22642194
TI  - Matrix metalloproteinase inhibitors as investigative tools in the pathogenesis
      and management of vascular disease.
AB  - Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade various
      components of the extracellular matrix (ECM). MMPs could also regulate the
      activity of several non-ECM bioactive substrates and consequently affect
      different cellular functions. Members of the MMPs family include collagenases,
      gelatinases, stromelysins, matrilysins, membrane-type MMPs, and others. Pro-MMPs
      are cleaved into active MMPs, which in turn act on various substrates in the ECM
      and on the cell surface. MMPs play an important role in the regulation of
      numerous physiological processes including vascular remodeling and angiogenesis.
      MMPs may also be involved in vascular diseases such as hypertension,
      atherosclerosis, aortic aneurysm, and varicose veins. MMPs also play a role in
      the hemodynamic and vascular changes associated with pregnancy and preeclampsia.
      The role of MMPs is commonly assessed by measuring their gene expression, protein
      amount, and proteolytic activity using gel zymography. Because there are no
      specific activators of MMPs, MMP inhibitors are often used to investigate the
      role of MMPs in different physiologic processes and in the pathogenesis of
      specific diseases. MMP inhibitors include endogenous tissue inhibitors (TIMPs)
      and pharmacological inhibitors such as zinc chelators, doxycycline, and
      marimastat. MMP inhibitors have been evaluated as diagnostic and therapeutic
      tools in cancer, autoimmune disease, and cardiovascular disease. Although several
      MMP inhibitors have been synthesized and tested both experimentally and
      clinically, only one MMP inhibitor, i.e., doxycycline, is currently approved by
      the Food and Drug Administration. This is mainly due to the undesirable side
      effects of MMP inhibitors especially on the musculoskeletal system. While most
      experimental and clinical trials of MMP inhibitors have not demonstrated
      significant benefits, some trials still showed promising results. With the advent
      of new genetic and pharmacological tools, disease-specific MMP inhibitors with
      fewer undesirable effects are being developed and could be useful in the
      management of vascular disease.

PMID- 22642207
TI  - [The sick lay beside the dead].

PMID- 22642208
TI  - [Standing skin folds and deep set eyes].

PMID- 22642209
TI  - [Working together instead of against each other].

PMID- 22642211
TI  - A proteomic approach to investigate the distribution and abundance of surface and
      internal Fasciola hepatica proteins during the chronic stage of natural liver
      fluke infection in cattle.
AB  - Fasciola hepatica, a trematode helminth, causes an economically important disease
      (fasciolosis) in ruminants worldwide. Proteomic analysis of the parasite provides
      valuable information to understand the relationship between the parasite and its
      host. Previous studies have identified various parasite proteins, some of which
      are considered as vaccine candidates or important drug targets. However, the
      approximate distribution and abundance of the proteins on the surface and within
      internal parts of the liver fluke are unknown. In this study, two fractions
      including surface protein fraction (representing surface part of the parasite,
      near subplasma membrane of the tegument and above the basal membrane of the
      tegument) and internal protein fraction (representing internal part of the
      parasite, mainly deeper sides of the tegument including subbasal membrane and
      other further internal elements of the parasite) were obtained. Components of
      these two fractions were investigated by an advanced proteomics approach using a
      high-definition mass spectrometer with nano electrospray ionization source
      coupled to a high-performance liquid chromatography system (nanoUPLC-ESI-qTOF
      MS). FABP1 was found highly abundant in the SPF fraction. Potentially novel F.
      hepatica proteins showing homology with AKT interacting protein (Xenopus
      tropicalis), sterol O-acyltransferase 2 (Homo sapiens), and integrin beta 7 (Mus
      musculus) were identified with high quantities in only the surface fraction of
      the parasite and may be possible candidates for future control strategies.

PMID- 22642212
TI  - Laser-thinning of MoS2: on demand generation of a single-layer semiconductor.
AB  - Single-layer MoS(2) is an attractive semiconducting analogue of graphene that
      combines high mechanical flexibility with a large direct bandgap of 1.8 eV. On
      the other hand, bulk MoS(2) is an indirect bandgap semiconductor similar to
      silicon, with a gap of 1.2 eV, and therefore deterministic preparation of single
      MoS(2) layers is a crucial step toward exploiting the large direct bandgap of
      monolayer MoS(2) in electronic, optoelectronic, and photovoltaic applications.
      Although mechanical and chemical exfoliation methods can be used to obtain high
      quality MoS(2) single layers, the lack of control in the thickness, shape, size,
      and position of the flakes limits their usefulness. Here we present a technique
      for controllably thinning multilayered MoS(2) down to a single-layer two
      dimensional crystal using a laser. We generate single layers in arbitrary shapes
      and patterns with feature sizes down to 200 nm and show that the resulting two
      dimensional crystals have optical and electronic properties comparable to that of
      pristine exfoliated MoS(2) single layers.

PMID- 22642213
TI  - Meal-feeding rodents and toxicology research.
AB  - Most laboratory rodents used for toxicology studies are fed ad libitum, with
      unlimited access to food. As a result, ad libitum-fed rodents tend to overeat.
      Research demonstrates that ad libitum-fed rodents are physiologically and
      metabolically different from rodents fed controlled amounts of food at scheduled
      times (meal-fed). Ad libitum-fed rodents can develop hypertriglyceridemia,
      hypercholesterolemia, diet-induced obesity, nephropathy, cardiomyopathy, and
      pituitary, pancreatic, adrenal, and thyroid tumors, conditions likely to affect
      the results of toxicology research studies. In contrast, meal-feeding
      synchronizes biological rhythms and leads to a longer life span, lower body
      weight, lower body temperature, hypertrophy of the small intestine, and
      synchronization of hepatic and digestive enzymes. The circadian rhythms present
      in nearly all living organisms are entrained by light intensity and food intake,
      and peripheral clocks in all organs of the body, especially the GI tract and
      liver, are particularly sensitive to food intake. Feeding schedule has been
      demonstrated to alter the toxicity and metabolism of drugs including sodium
      valproate, chloral hydrate, acetaminophen, gentamicin, and methotrexate. Feeding
      schedule alters the expression of genes that code for Phase I, II, and III
      proteins, thereby altering the rate and amplitude of drug disposition. Rhythms of
      plasma insulin and glucagon that fluctuate with food ingestion are also altered
      by feeding schedule; ad libitum feeding promotes hyperinsulinemia which is a
      precursor for developing diabetes. The emerging field of chronopharmacology, the
      interaction of biological rhythms and drugs, will lead to optimizing the design
      and delivery of drugs in a manner that matches biological rhythms, but it is wise
      for toxicology researchers to consider feeding schedule when designing these
      experiments. It has been 10 years since the Society for Toxicologic Pathology
      voiced its position that feeding schedule is an important variable that should be
      controlled in toxicology experiments, and research continues to underscore this
      position.

PMID- 22642215
TI  - Eye movements reveal how task difficulty moulds visual search.
AB  - In two experiments we investigated the relationship between eye movements and
      performance in visual search tasks of varying difficulty. Experiment 1 provided
      evidence that a single process is used for search among static and moving items.
      Moreover, we estimated the functional visual field (FVF) from the gaze
      coordinates and found that its size during visual search shrinks with increasing
      task difficulty. In Experiment 2, we used a gaze-contingent window and confirmed
      the validity of the size estimates. The experiment also revealed that breakdown
      in robustness against item motion is related to item-by-item search, rather than
      search difficulty per se. We argue that visual search is an eye-movement-based
      process that works on a continuum, from almost parallel (where many items can be
      processed within a fixation) to completely serial (where only one item can be
      processed within a fixation).

PMID- 22642216
TI  - Is the whole really more than the sum of its parts? Estimates of average size and
      orientation are susceptible to object substitution masking.
AB  - We have a remarkable ability to accurately estimate average featural information
      across groups of objects, such as their average size or orientation. It has been
      suggested that, unlike individual object processing, this process of feature
      averaging occurs automatically and relatively early in the course of perceptual
      processing, without the need for objects to be processed to the same extent as is
      required for individual object identification. Here, we probed the processing
      stages involved in feature averaging by examining whether feature averaging is
      resistant to object substitution masking (OSM). Participants estimated the
      average size (Experiment 1) or average orientation (Experiment 2) of groups of
      briefly presented objects. Masking a subset of the objects using OSM reduced the
      extent to which these objects contributed to estimates of both average size and
      average orientation. Contrary to previous findings, these results suggest that
      feature averaging benefits from late stages of processing, subsequent to the
      initial registration of featural information.

PMID- 22642214
TI  - Correction of brain oligodendrocytes by AAVrh.10 intracerebral gene therapy in
      metachromatic leukodystrophy mice.
AB  - Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder characterized
      by accumulation of sulfatides in glial cells and neurons, the result of an
      inherited deficiency of arylsulfatase A (ARSA; EC 3.1.6.8) and myelin
      degeneration in the central and peripheral nervous systems. No effective
      treatment is currently available for the most frequent late infantile (LI) form
      of MLD, which results in rapid neurological degradation and early death after the
      onset of clinical manifestations. To potentially arrest or reverse disease
      progression, ARSA enzyme must be rapidly delivered to brain oligodendrocytes of
      patients with LI MLD. We previously showed that brain gene therapy with adeno
      associated virus serotype 5 (AAV5) driving the expression of human ARSA cDNA
      under the control of the murine phosphoglycerate kinase (PGK) promoter alleviated
      most long-term disease manifestations in MLD mice. Herein, we evaluated the short
      term effects of AAVrh.10 driving the expression of human ARSA cDNA under the
      control of the cytomegalovirus/beta-actin hybrid (CAG/cu) promoter in 8-month-old
      MLD mice that already show marked sulfatide accumulation and brain pathology.
      Within 2 months, and in contrast to results with the AAV5-PGK-ARSA vector, a
      single intrastriatal injection of AAVrh.10cuARSA resulted in correction of brain
      sulfatide storage, accumulation of specific sulfatide species in
      oligodendrocytes, and associated brain pathology in the injected hemisphere.
      Better potency of the AAVrh.10cuARSA vector was mediated by higher neuronal and
      oligodendrocyte transduction, axonal transport of the AAVrh.10 vector and ARSA
      enzyme, as well as higher CAG/cu promoter driven expression of ARSA enzyme. These
      results strongly support the use of AAVrh.10cuARSA vector for intracerebral gene
      therapy in rapidly progressing early-onset forms of MLD.

PMID- 22642217
TI  - The effects of inversion and familiarity on face versus body cues to person
      recognition.
AB  - Extensive research has focused on face recognition, and much is known about this
      topic. However, much of this work seems to be based on an assumption that faces
      are the most important aspect of person recognition. Here we test this assumption
      in two experiments. We show that when viewers are forced to choose, they do use
      the face more than the body, both for familiar (trained) person recognition and
      for unfamiliar person matching. However, we also show that headless bodies are
      recognized and matched with very high accuracy. We further show that processing
      style may be similar for faces and bodies, with inversion effects found in all
      cases (bodies with heads, faces alone and bodies alone), and evidence that
      mismatching bodies and heads causes interference. We suggest that recent findings
      of no inversion effect when stimuli are headless bodies may have been obtained
      because the stimuli led viewers to focus on nonbody aspects (e.g., clothes) or
      because pose and identity tasks led to somewhat different processing. Our results
      are consistent with holistic processing for bodies as well as faces.

PMID- 22642218
TI  - "Hot" facilitation of "cool" processing: emotional distraction can enhance
      priming of visual search.
AB  - Emotional stimuli often capture attention and disrupt effortful cognitive
      processing. However, cognitive processes vary in the degree to which they require
      effort. We investigated the impact of emotional pictures on visual search and on
      automatic priming of search. Observers performed visual search after task
      irrelevant neutral or emotionally evocative photographs. Search performance was
      generally impaired after emotional pictures, but improvement (measured both with
      inverse efficiency and sensitivity to briefly presented targets) as a function of
      incremental between-trial target-color repetition was strongest after emotional
      pictures. For observers showing the largest general effect of emotional pictures,
      there was a reversal, with performance becoming better after neutral pictures
      than after four or more trials containing the same search target. This suggests
      that although emotional pictures disrupt effortful attention, this detriment can
      be overcome--to the point where performance is enhanced by emotional stimuli-
      when the task involves prepotent task priorities.

PMID- 22642219
TI  - Study of the fundamental units of novel semiconductor materials: structures,
      energetics, and thermodynamics of the Ge-Sn and Si-Ge-Sn molecular systems.
AB  - The binary Ge(y)Sn(z) and ternary Si(x)Ge(y)Sn(z) molecular systems containing up
      to five atoms were investigated by means of density functional theory and coupled
      cluster calculations. The minimum energy structures were calculated and higher
      energy isomers are also proposed. The atomization energies of the ground state
      isomers were calculated by the CCSD(T) method with correlation consistent basis
      sets up to quadruple-zeta quality. The resulting values were extrapolated to the
      complete basis set limit and corrected by an approximate evaluation of the spin
      orbit effect. Energetic properties such as binding, fragmentation and mixing
      energies, and HOMO-LUMO gap were analyzed as a function of the cluster size and
      composition. By using empirically adjusted atomization energies and DFT harmonic
      frequencies, the thermal functions were evaluated, and a thermodynamic database
      for the Si-Ge-Sn system was built, containing data for 55 gaseous species. On
      this basis, equilibrium calculations were performed in the temperature interval
      1600-2200 K aimed at predicting the composition of the gas phase under various
      conditions. The results presented here can be of interest to improve the
      microscopic knowledge of Ge-Sn and Si-Ge-Sn materials, which are among the most
      promising candidates for advanced applications in the field of electronic and
      optoelectronic components, both as epitaxially grown layers and as nanocrystal
      quantum dots.

PMID- 22642220
TI  - Aluminum chloride activation of chloro-boronsubphthalocyanine: a rapid and
      flexible method for axial functionalization with an expanded set of nucleophiles.
AB  - We have developed a process whereby chloro-boronsubphthalocyanine (Cl-BsubPc) and
      other BsubPcs are activated to reaction with oxygen, sulfur, and nitrogen based
      nucleophiles by treatment with aluminum chloride under mild conditions. This
      allows for the scope of atoms chemically bound to the boron atom to be expanded
      beyond those derived from the traditional oxygen and carbon based nucleophiles.
      The successful formation of thiophenoxy and phenylamino derivatives of BsubPc was
      confirmed spectroscopically and by X-ray crystallography of single crystals. We
      have proposed a detailed mechanism for this process based on experimental
      observation and NMR spectroscopy ((1)H, (11)B, and (27)Al) which involves
      formation of a complex between a halo-BsubPc and AlCl(3) (which we denote
      BsubPc(Cl).Al(Cl')(3)). Our observations indicate that the action of phenol on
      BsubPc(Cl).Al(Cl')(3) does not involve direct reaction at the boron atom; rather
      phenol first reacts at the aluminum atom along the way to the formation of a new
      intermediate complex BsubPc(OPh).Al(O'Ph)(3). The consequence is that the rate of
      this process is independent of the nature of the starting BsubPc. Cl-BsubPc and
      Br-BsubPc as well as BsubPcs with peripheral substitutents all react to form
      their respective phenoxy derivatives at the same rate. Quenching of
      BsubPc(OPh).Al(O'Ph)(3) with a Lewis base ultimately produces a new bond between
      the phenol nucleophile and the boron atom of the BsubPc.

PMID- 22642221
TI  - Imprecise definitions of starting points in retrospectively reviewing potential
      organ donors causes confusion: call for a reproducible method like 'imminent
      brain death'.
AB  - Low donor supply and the high demand for transplantable organs is an
      international problem. The efficiency of organ procurement is often expressed by
      donor conversion rates (DCRs). These rates differ among countries, but a uniform
      starting point for defining a potential heart-beating donor is lacking. Imprecise
      definitions cause confusion; therefore, we call for a reproducible method like
      imminent brain death (IBD), which contains criteria in detail to determine
      potential heart-beating donors. Medical charts of 4814 patients who died on an
      ICU in Dutch university hospitals between January 2007 and December 2009 were
      reviewed for potential heart-beating donors. We compared two starting points:
      'Severe Brain Damage' (SBD) (old definition) and IBD (new definition), which
      differ in the number of absent brainstem reflexes. Of the potential donors
      defined by IBD 45.6% fulfilled the formal brain death criteria, compared with
      33.6% in the larger SBD group. This results in a higher DCR in the IBD group (40%
      vs. 29.5%). We illustrated important differences in DCRs when using two different
      definitions, even within one country. To allow comparison among countries and
      hospitals, one universal definition of a potential heart-beating donor should be
      used. Therefore, we propose the use of IBD.

PMID- 22642222
TI  - Diagnostic role of microRNA expression profile in the serum of pregnant women
      with fetuses with neural tube defects.
AB  - The discovery of placental microRNAs (miRNAs) in maternal serum has opened up new
      possibilities for non-invasive prenatal diagnosis. However, the expression of
      miRNAs in the serum of pregnant women with fetuses with neural tube defects
      (NTDs) has not been characterized. In this article, we explored serum miRNAs as
      potential biomarkers in the serum of pregnant women with NTD fetuses. By using a
      miRNA microarray that covers 887 human miRNAs, we revealed 17 miRNAs with
      significant change in expression in serum of pregnant women with NTD fetuses and
      women with normal pregnancies. Quantitative reverse-transcription PCR (qRT-PCR)
      analysis validated that the expression for six miRNAs (miR-142-3p, miR-144, miR
      720, miR-575, miR-765, and miR-1182) was up-regulated and that for miR-1275 was
      down-regulated. To determine whether these miRNAs were related to pregnancy, we
      compared the miRNA levels in pre- and post-delivery maternal serum samples. Six
      of these miRNAs were rapidly reduced in post-delivery serum (p < 0.05). Moreover,
      by receiver operating characteristic (ROC) curve analysis, the area under the ROC
      curve (AUC) of combining these six miRNAs was 0.803 (p < 0.001). Thus, we reveal
      six pregnancy-associated miRNAs that are deregulated in the serum of pregnant
      women with NTD fetuses and highlight the clinical potential of serum miRNAs as
      biomarkers for diagnosis and prognostication of fetal NTDs.

PMID- 22642223
TI  - The role of corticosteroids in the management of chronic subdural hematoma: a
      systematic review.
AB  - The role of corticosteroids in the management of chronic subdural hematoma (CSDH)
      remains a matter of debate. Standard surgical treatment has recurrence rates
      reported between 4 and 26%. We reviewed the safety and effectiveness of
      corticosteroids both as a monotherapy and as an adjunct to surgery in patients
      with CSDH. PubMed-MEDLINE, EMBASE and Cochrane databases were searched in July
      2011 for randomized controlled trials and for prospective and retrospective
      cohort studies, reporting on 10 or more adult patients with CSDH. Quality was
      assessed according to the STROBE checklist. Corticosteroid monotherapy and
      surgery with corticosteroids as an adjunct were compared with no treatment or
      surgery only, with regard to lethality, neurological outcome, secondary
      intervention and complications. Five observational studies were included in this
      review. There was no randomized allocation of treatment in any study. Secondary
      intervention rates ranged from 3 to 28%, lethality rates ranged from 0 to 13%,
      and good outcome was seen in 83-100%. Hyperglycemia occurred more often in
      patients treated with corticosteroids. In only two studies, one case of
      gastrointestinal bleeding was observed. Five observational studies suggest that
      corticosteroids might be beneficial in the treatment of CSDH; however, there is a
      lack of well-designed trials that support or refute the use of corticosteroids in
      CSDH. These results encourage further randomized clinical trials to establish the
      role of corticosteroids in CSDH.

PMID- 22642224
TI  - Amyloid substance within stenotic aortic valves promotes mineralization.
AB  - AIMS: Accumulation of apolipoproteins may play an important role in the
      pathobiology of calcific aortic valve disease (CAVD). We aimed to explore the
      hypothesis that apolipoprotein-derived amyloid could play a role in the
      development of CAVD. METHODS AND RESULTS: In 70 explanted CAVD valves and 15
      control non-calcified aortic valves, we assessed the presence of amyloid by using
      Congo red staining. Immunohistochemistry was performed to document the presence
      of apolipoprotein AI (Apo-AI). Apoptosis was documented by terminal
      deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) studies performed in
      control and CAVD valves. Control valves were free of amyloid. Deposition of
      amyloid was detected in all CAVD valves, and the amount was positively correlated
      with plasma high-density lipoprotein and Apo-AI levels. Apo-AI within CAVD valves
      co-localized with intense staining of fibrillar amyloid. In turn, deposition of
      amyloid co-localized with apoptosis near mineralized areas. Isolation of amyloid
      fibrils confirmed that Apo-AI is a major component of amyloid deposits in CAVD.
      In vitro, CAVD-derived amyloid extracts increased apoptosis and mineralization of
      isolated aortic valvular interstitial cells. CONCLUSION: Apo-AI is a major
      component of amyloid substance present within CAVD valves. Furthermore, amyloid
      deposits participate in mineralization in CAVD by promoting apoptosis of valvular
      interstitial cells.

PMID- 22642225
TI  - Vacuolar ATPase subunit H is essential for the survival and moulting of Locusta
      migratoria manilensis.
AB  - Vacuolar (H(+) )-ATPase (V-ATPase) functions as an electrogenic pump,
      transporting protons from the cytoplasm to the extracellular fluid to generate
      cell-negative membrane voltage. The V-ATPase subunit H, encoded by Vhasfd, is
      required for V-ATPase activity. In this study, the gene encoding V-ATPase subunit
      H from Locusta migratoria manilensis was cloned, and designated as Lm-Vhasfd. The
      complete cDNA sequence is 2018 bp, with an open reading frame encoding 515 amino
      acid residues. Semi-quantitative reverse transcription PCR (RT-PCR) showed that
      Lm-Vhasfd transcription is high in the haemolymph, midgut, trunk and leg, but
      relatively low in the fat body and head tissues. Injection with a specific double
      strand RNA (dsRNA) led to a significant decrease in Lm-Vhasfd mRNA, V-ATPase
      enzyme activity and ATP concentration. Bioassays showed that silencing Lm-Vhasfd
      led to the death of individuals and various moulting defects. The accumulative
      mortality of the RNA interference (RNAi) mutant 11 days post-injection was 96.7%,
      which was conspicuously higher than that seen in wild type locusts. These RNAi
      phenotypes demonstrate that Lm-Vhasfd is essential for the growth and moulting of
      L. migratoria manilensis.

PMID- 22642226
TI  - Open non-microsurgical, laparoscopic or open microsurgical varicocelectomy for
      male infertility: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To compare various techniques of open non-microsurgical, laparoscopic
      or microsurgical varicocelectomy procedures to describe the best method for
      treating varicocele in infertile men. PATIENTS AND METHODS: We searched PubMed,
      Embase, the Cochrane Library, the Institute for Scientific Information (ISI) -
      Science Citation Index and the Chinese Biomedicine Literature Database up to June
      2011. Only randomized controlled trials (RCTs) were included in the present
      study. The outcome measures assessed were pregnancy rate (primary), the incidence
      of recurrent varicocele, time to return to work, the incidence of postoperative
      hydrocele and operation duration (secondary). Two authors independently assessed
      the study quality and extracted data. All data were analysed using Review Manager
      (version 5.0). RESULTS: The present study included four randomized controlled
      trials comprising 1,015 patients in total. At the follow-up endpoints, patients
      who had undergone microsurgery showed a significant advantage over those who had
      undergone open varicocelectomy in terms of pregnancy rate (odds ratio [OR]= 1.63,
      95% confidence interval [CI]: 1.19-2.23]. There was no significant difference
      between laparoscopic and open varicocelectomy (OR = 1.11, 95% CI: 0.65-1.88) or
      between microsurgery and laparoscopic varicocelectomy (OR = 1.37, 95% CI: 0.84
      2.24). The incidences of recurrent varicocele and postoperative hydrocele were
      significantly lower after microsurgery than after laparoscopic or open
      varicocelectomy. The time to return to work after microsurgery and laparoscopic
      varicocelectomy was significantly shorter than that after open varicocelectomy.
      The operation duration of microsurgical varicocelectomy was longer than that of
      laparoscopic or open varicocelectomy. CONCLUSIONS: Current evidence indicates
      that microsurgical varicocelectomy is the most effective and least morbid method
      among the three varicocelectomy techniques for treating varicocele in infertile
      men. More high-quality, multicentre, long-term RCTs are required to verify the
      findings.

PMID- 22642227
TI  - Docosahexaenoic acid status at 9 months is inversely associated with
      communicative skills in 3-year-old girls.
AB  - The objective of the present observational study was to investigate if the
      docosahexaenoic acid (DHA) status assessed in infant erythrocytes (RBC) at 9
      months was associated with the age when the infants reach developmental
      milestones and their psychomotor function at 3 years of age. Three hundred eleven
      healthy Danish children were followed from 9 months to 3 years of age (the SKOT
      cohort). RBC fatty acid composition was analysed by gas chromatography in 272 of
      the children. Milestone age was collected by questionnaires at 9 and 18 months
      and psychomotor development at 3 years of age was assessed by the parents using
      third edition of the Ages and Stages Questionnaire (ASQ-3). RBC DHA levels ranged
      from 2.2% to 12.6% of the RBC fatty acids. The age of reaching milestones
      correlated with psychomotor development, particularly with gross motor function
      at 3 years. An association between milestones and later personal and social
      skills was also observed, but only for girls. In girls, RBC-DHA was found to be
      inversely correlated with communication at 3 years of age (odds ratio = 0.69, 95%
      confidence interval: 0.56-0.86, P = 0.001), but no other associations with
      psychomotor development or milestones were found. The results from study indicate
      that DHA status at 9 months may not have a pronounced beneficial effect on
      psychomotor development in early childhood and that communicative skills at 3
      years of age may even be inversely associated with early RBC-DHA levels in girls.

PMID- 22642229
TI  - Cultural meaning of perceived control: a meta-analysis of locus of control and
      psychological symptoms across 18 cultural regions.
AB  - Integrating more than 40 years of studies on locus of control (LOC), this meta
      analysis investigated whether (a) the magnitude of the relationship between LOC
      and psychological symptoms differed among cultures with distinct individualist
      orientations and (b) depression and anxiety symptoms yielded different patterns
      of cultural findings with LOC. We included studies that examined global self
      ratings of LOC and at least 1 of the criterion variables in nonclinical samples
      (age range: 18-80 years). Data were analyzed on the basis of 152 independent
      samples, representing the testing of 33,224 adults across 18 cultural regions.
      Results revealed moderately strong relationships for external LOC with depression
      symptoms (k = 123, N = 28,490, r = .30, 95% confidence interval [CI] [.27, .32])
      and anxiety symptoms (k = 65, N = 13,208, r = .30, 95% CI [.27, .33]).
      Individualism explained 20% of unique variance only in the external LOC-anxiety
      relationship: The link between external LOC and anxiety symptoms was weaker for
      collectivist societies (k = 8, N = 2,297, r = .20, 95% CI [.13, .28]) compared
      with individualist societies (k = 54, N = 9,887, r = .32, 95% CI [.29, .34]).
      Such cultural differences were attributed to the reduced emphasis on agentic
      goals in more collectivist societies. It is noteworthy that external LOC does not
      carry the same negative connotations across cultures, and members of collectivist
      societies may be more ready to endorse such items. Culture has been examined at
      the country level, and the findings may not be applicable to any particular
      person in a cultural region. Implications for integrating cultural meaning of
      perceived control into formulation of theories, research design, and intervention
      programs are discussed.

PMID- 22642230
TI  - Social network changes and life events across the life span: a meta-analysis.
AB  - For researchers and practitioners interested in social relationships, the
      question remains as to how large social networks typically are, and how their
      size and composition change across adulthood. On the basis of predictions of
      socioemotional selectivity theory and social convoy theory, we conducted a meta
      analysis on age-related social network changes and the effects of life events on
      social networks using 277 studies with 177,635 participants from adolescence to
      old age. Cross-sectional as well as longitudinal studies consistently showed that
      (a) the global social network increased up until young adulthood and then
      decreased steadily, (b) both the personal network and the friendship network
      decreased throughout adulthood, (c) the family network was stable in size from
      adolescence to old age, and (d) other networks with coworkers or neighbors were
      important only in specific age ranges. Studies focusing on life events that occur
      at specific ages, such as transition to parenthood, job entry, or widowhood,
      demonstrated network changes similar to such age-related network changes.
      Moderator analyses detected that the type of network assessment affected the
      reported size of global, personal, and family networks. Period effects on network
      sizes occurred for personal and friendship networks, which have decreased in size
      over the last 35 years. Together the findings are consistent with the view that a
      portion of normative, age-related social network changes are due to normative,
      age-related life events. We discuss how these patterns of normative social
      network development inform research in social, evolutionary, cultural, and
      personality psychology.

PMID- 22642231
TI  - Effect of guided relaxation and imagery on falls self-efficacy: a randomized
      controlled trial.
AB  - OBJECTIVES: To examine the effects of guided relaxation and imagery (GRI) on
      improvement in falls self-efficacy in older adults who report having a fear of
      falling. DESIGN: Randomized, controlled trial with allocation to GRI or guided
      relaxation with music of choice. SETTING: General community. PARTICIPANTS: Ninety
      one men and women aged 60 to 92. INTERVENTION: Participants were randomized to
      listen to a GRI audio compact disk (intervention group) or a guided relaxation
      audio compact disk and music of choice (control group) twice a week for 6 weeks
      for 10 minutes per session. MEASUREMENTS: Primary outcome measure was the Short
      Falls Efficacy Scale-International (FES-I). Secondary outcome measures were the
      Leisure Time Exercise Questionnaire (LTEQ) and the Timed Up and Go (TUG) mobility
      test. RESULTS: GRI participants reported greater improvements on the Short FES-I
      (P = .002) and LTEQ (P = .001) scores and shorter time on the TUG (P = .002) than
      the guided relaxation and music-of-choice group. CONCLUSION: GRI was more
      effective at increasing falls self-efficacy and self-reported leisure time
      exercise and reducing times on a simple mobility test than was guided relaxation
      with music of choice. GRI is an effective, simple, low-cost tool for older adults
      to improve falls self-efficacy and leisure time exercise behaviors.

PMID- 22642232
TI  - Reduced release and binding of perforin at the immunological synapse underlies
      the age-related decline in natural killer cell cytotoxicity.
AB  - Physiological aging is accompanied by a marked reduction in natural killer (NK)
      cell cytotoxicity (NKCC) at the single cell level, but the underlying mechanisms
      are unknown. To address this issue, we isolated NK cells from healthy young (<=
      35 years) and old (<= 60 years) subjects and examined the effect of age on events
      fundamental to the process of NKCC. Simultaneous assessment of NKCC and NK cell
      target cell conjugate formation revealed a marked age-associated decline in NK
      cell killing but comparable conjugate formation, indicating a post-target cell
      binding defect was responsible for impaired NKCC. Despite a reduction in the
      proportion of NK cells expressing the activatory receptor NKp46, NK cells from
      old donors were not hyporesponsive to stimulation, as no age-associated
      difference was observed in the expression of the early activation marker CD69
      following target cell coculture. Furthermore, intracellular levels of the key
      cytotoxic effector molecules perforin and granzyme B, and the fusion of secretory
      lysosomes with the NK cell membrane were also similar between the two groups.
      However, when we examined the binding of the pore-forming protein perforin to the
      surface of its target cell, an event that correlated strongly with target cell
      lysis, we found the percentage of perforin positive target cells was lower
      following coculture with NK cells from old subjects. Underlying this reduction in
      binding was an age-associated impairment in perforin secretion, which was
      associated with defective polarization of lytic granules towards the
      immunological synapse. We propose that reduced perforin secretion underlies the
      reduction in NKCC that accompanies physiological aging.

PMID- 22642234
TI  - Comparative Studies on the Interaction Between Bovine beta-lacto-globulin Type A
      and B and a New Designed Pd(II) Complex with Anti-tumor Activity at Different
      Temperatures.
AB  - Abstract   An new water-soluble Pd(II) complex, 2,2'-bipyridin n-butyl
      dithiocarbamato Pd(II) nitrate has been synthesized. The Pd(II) complex has been
      characterized by elemental analysis and conductivity measurements as well as
      spectroscopic methods such as infrared, 1H NMR, and ultraviolet-visible. The
      interaction between this new design Pd(II)-complex, an anti-tumor component, with
      carrier proteins of beta-lactoglobulin-A and -B (BLG-A and -B) were studied at
      different temperatures of 27, 37, 42, and 47  degrees C by fluorescence
      spectroscopy and far-UV circular dichroism (CD) spectrophotometric techniques. A
      strong fluorescence quenching interaction of Pd(II) complex with BLG-A and -B was
      observed at different temperatures. The binding parameters were evaluated by
      fluorescence quenching method. The thermodynamic parameters, including DeltaH
      degrees , DeltaS degrees , and DeltaG degrees  were calculated by fluorescence
      quenching method indicated that the electrostatic and hydrophobic forces might
      play a major role in the interactions of Pd(II) complex with BLG-A and -B,
      respectively. The distances between donors (Trps of the BLG-A and -B) and
      acceptor (Pd(II) complex) were obtained according to the fluorescence resonance
      energy transfer (FRET). Far-UV CD studies showed that the Pd(II) complex did not
      represent any significant changes in the secondary structures of BLG- A and -B.
      The difference in the interaction properties observed for BLG-A and -B with
      Pd(II) complex is related to the difference in the amino acid sequences between
      these two variants.

PMID- 22642228
TI  - Major depressive disorder is associated with broad impairments on
      neuropsychological measures of executive function: a meta-analysis and review.
AB  - Cognitive impairments are now widely acknowledged as an important aspect of major
      depressive disorder (MDD), and it has been proposed that executive function (EF)
      may be particularly impaired in patients with MDD. However, the existence and
      nature of EF impairments associated with depression remain strongly debated.
      Although many studies have found significant deficits associated with MDD on
      neuropsychological measures of EF, others have not, potentially due to low
      statistical power, task impurity, and diverse patient samples, and there have
      been no recent, comprehensive, meta-analyses investigating EF in patients with
      MDD. The current meta-analysis uses random-effects models to synthesize 113
      previous research studies that compared participants with MDD to healthy control
      participants on at least one neuropsychological measure of EF. Results of the
      meta-analysis demonstrate that MDD is reliably associated with impaired
      performance on neuropsychological measures of EF, with effect sizes ranging from
      0.32 to 0.97. Although patients with MDD also have slower processing speed, motor
      slowing alone cannot account for these results. In addition, some evidence
      suggests that deficits on neuropsychological measures of EF are greater in
      patients with more severe current depression symptoms, and those taking
      psychotropic medications, whereas evidence for effects of age was weaker. The
      results are consistent with the theory that MDD is associated with broad
      impairment in multiple aspects of EF. Implications for treatment of MDD and
      theories of EF are discussed. Future research is needed to establish the
      specificity and causal link between MDD and EF impairments.

PMID- 22642233
TI  - Intercellular calcium waves in primary cultured rat mesenteric smooth muscle
      cells are mediated by connexin43.
AB  - Intercellular Ca(2+) wave propagation between vascular smooth muscle cells (SMCs)
      is associated with the propagation of contraction along the vessel. Here, we
      characterize the involvement of gap junctions (GJs) in Ca(2+) wave propagation
      between SMCs at the cellular level. Gap junctional communication was assessed by
      the propagation of intercellular Ca(2+) waves and the transfer of Lucifer Yellow
      in A7r5 cells, primary rat mesenteric SMCs (pSMCs), and 6B5N cells, a clone of
      A7r5 cells expressing higher connexin43 (Cx43) to Cx40 ratio. Mechanical
      stimulation induced an intracellular Ca(2+) wave in pSMC and 6B5N cells that
      propagated to neighboring cells, whereas Ca(2+) waves in A7r5 cells failed to
      progress to neighboring cells. We demonstrate that Cx43 forms the functional GJs
      that are involved in mediating intercellular Ca(2+) waves and that co-expression
      of Cx40 with Cx43, depending on their expression ratio, may interfere with Cx43
      GJ formation, thus altering junctional communication.

PMID- 22642235
TI  - Temporal dynamics in auditory perceptual learning: impact of sequencing and
      incidental learning.
AB  - Training can improve perceptual sensitivities. We examined whether the temporal
      dynamics and the incidental versus intentional nature of training are important.
      Within the context of a birdsong rate discrimination task, we examined whether
      the sequencing of pretesting exposure to the stimuli mattered. Easy-to-hard
      (progressive) sequencing of stimuli during preexposure led to a more accurate
      performance with the critical difficult contrast and greater generalization to
      new contrasts in the task, compared with equally variable training in either a
      random or an antiprogressive order. This greater accuracy was also evident when
      participants experienced the progressively sequenced stimuli in a different
      incidental learning task that did not involve direct auditory training. The
      results clearly show the importance of temporal dynamics (sequencing) in learning
      and show that the progressive training advantages cannot be fully explained by
      direct associations between stimulus features and the corresponding responses.
      The current findings are consistent with a hierarchical account of perceptual
      learning, among other possibilities, but not with explanations that focus on
      stimulus variability.

PMID- 22642236
TI  - Interpolated task effects on direct and mediated false recognition: effects of
      initial recall, recognition, and the ironic effect of guessing.
AB  - In two experiments, participants studied two types of word lists. Direct lists
      were taken from the Deese-Roediger-McDermott (DRM) paradigm (e.g., water, bridge,
      run) and contained words directly related to a nonpresented critical item (CI;
      e.g., river, Roediger & McDermott, 1995). Mediated lists (e.g., faucet, London,
      jog) contained words related to the CI through a nonpresented mediator. After
      each study list, participants completed either a recall test, a recall test with
      a warning about the CI, arithmetic problems, or a recognition test, or they
      guessed the CI. On a final recognition test, both warning and guessing decreased
      direct false recognition but increased mediated false recognition, an ironic
      effect of guessing. An initial recognition test also increased final mediated
      false recognition. We argue that warning and guessing tasks strengthened
      associative pathways to the CI, increased the accessibility of associated
      mediators, and increased monitoring for the CI at test. Increased monitoring was
      able to reduce CIs from direct, but not mediated, lists.

PMID- 22642237
TI  - On the role of working memory in spatial contextual cueing.
AB  - The human visual system receives more information than can be consciously
      processed. To overcome this capacity limit, we employ attentional mechanisms to
      prioritize task-relevant (target) information over less relevant (distractor)
      information. Regularities in the environment can facilitate the allocation of
      attention, as demonstrated by the spatial contextual cueing paradigm. When
      observers are exposed repeatedly to a scene and invariant distractor information,
      learning from earlier exposures enhances the search for the target. Here, we
      investigated whether spatial contextual cueing draws on spatial working memory
      resources and, if so, at what level of processing working memory load has its
      effect. Participants performed 2 tasks concurrently: a visual search task, in
      which the spatial configuration of some search arrays occasionally repeated, and
      a spatial working memory task. Increases in working memory load significantly
      impaired contextual learning. These findings indicate that spatial contextual
      cueing utilizes working memory resources.

PMID- 22642238
TI  - New strategies for managing anemia of chronic kidney disease.
AB  - Anemia is a prevalent and premature comorbidity in chronic kidney disease (CKD)
      and associated with multiple adverse clinical consequences including increased
      mortality. Today Erythropoiesis-stimulating agents (ESAs), together with iron
      supplementation, are the cornerstones of therapy for correcting anemia in CKD
      patients. As no generally accepted dosing algorithms for these agents exist,
      current recommendations prefer a partial but not complete anemia correction
      thereby favoring a more conservative and individualized ESA and iron dosing. Here
      we discuss in detail current evidence derived from large randomized trials about
      the proposed hemoglobin targets to aim at in CKD and End-Stage renal disease
      patients and report recent data from the thriving European market of biosimilar
      erythropoietins. We summarize promising investigational strategies including
      peginesatide and prolyl hydroxylase inhibitors for stabilization of the hypoxia
      inducible factor and provide a clinical review of novel high dose iron
      formulations like ferumoxytol or iron (III)-carboxymaltose. Taking these findings
      together, treatment strategies for anemia of CKD have got considerably more
      complicated so that a careful balance between maximization of patient's quality
      of life while minimizing all risks associated with anemia treatment has become a
      major task of current nephrology.

PMID- 22642239
TI  - Atrial fibrillation in patients undergoing surgical revascularization: an update
      on pharmacologic prophylaxis.
AB  - Atrial fibrillation occurs in 20-50% of patients after surgical revascularization
      (40% have more than 1 episode), with a peak between 2nd and 3rd postoperative
      days. Postoperative atrial fibrillation (POAF) has been associated with an
      increase in adverse events, length of hospital stay and, therefore, cost of care,
      and late mortality. A higher risk profile in patients who develop POAF may
      contribute to the higher late mortality rate. The pathogenesis of PAOF is multi
      factorial: transient ischemia during surgical procedure, neurohormonal
      activation, electrolyte imbalance, fluid overload and finally an exaggerated
      inflammatory response have been associated with POAF. Advanced age, an history of
      AF or heart failure and, finally, COPD are clinically independent risk factors
      related to POAF. The lower incidence of POAF reported after off-pump CABG in
      comparison to conventional cardiopulmonary by-pass CABG techniques has not been
      confirmed. The administration of antiarrhythmic drugs (amiodarone, metoprolol,
      sotalol and recently propafenone and landiolol) before and /or after surgical
      procedure has been extensively investigated and most of the investigators have
      demonstrated a favorable effect on POAF incidence. The decreased incidence of
      POAF and related shorter hospital stay by PUFA administration during
      hospitalization needs to be confirmed. Preliminary results suggest that pre
      treatment with the antianginal drug ranolazine may significantly decrease POAF
      incidence. Treatments directed to antagonize inflammation are presently under
      investigation. Recently, a randomized study with naproxen, although effective on
      POAF, was interrupted due to increased risk of nephrotoxicty. Despite different
      action mechanisms, both hydrocortisone and statins have been shown to decrease
      post-operative AF risk. No data at present exist on the effects of association of
      these drugs. Aim of the present review was to update the current practice and
      report the recent results of research in the prophylaxis of atrial fibrillation
      in patients undergoing CABG.

PMID- 22642240
TI  - Where are we standing with the screening of healthy population for celiac
      disease?

PMID- 22642241
TI  - Fast food intake among Iranian adults: is it related to diet quality and
      cardiovascular risk factors?

PMID- 22642242
TI  - Prevalence of occult celiac disease in healthy Iranian school age children.
AB  - BACKGROUND:   Several studies have shown the prevalence of celiac disease (CD) to
      be around 1% in Iran, which is similar to the worldwide prevalence. There is
      scant information on occult CD in apparently healthy school age children. This
      study, as the first such study in Iran, aims to determine the prevalence of
      occult CD in healthy Iranian school age children. METHODS: In this cross
      sectional study, we screened healthy school age children for CD by serum IgA and
      IgA anti-tissue transglutaminase antibody (tTG) levels. Measurement of these
      antibodies was by enzyme linked immunosorbent assay. A recheck of positive tTG
      tests was performed and patients who tested positive underwent endoscopic
      duodenal biopsies. The biopsy samples were scored according to the Marsh
      classification by an experienced pathologist. RESULTS: A total of 634 children
      (314 males, 320 females; mean age: 12.8 years) were included in the study. All
      children and/or their parents completed a questionnaire and children underwent an
      initial physical examination to determine study eligibility. Positive serum tTG
      was noted in 3 (0.5%; 2 females) out of 634 patients. Duodenal biopsies were
      consistent with CD in these 3 subjects. The mean age of patients with CD was 14.3
      years (range: 12-17 years). The female to male ratio was 2:1. These cases had no
      signs and symptoms, but a gluten-free diet was recommended according to
      pathologic changes in their small bowels and results of the tTG test. CONCLUSION:
      The prevalence of occult CD in these children is 0.5%, which is half of the
      prevalence of CD in Iranian adults. The anti-tTG concentration at initial
      serological CD screening is highly informative in determining occult cases of CD.
      The question is whether all non-symptomatic cases should be treated with a gluten
      free diet or not.

PMID- 22642243
TI  - Fast food consumption in Iranian adults; dietary intake and cardiovascular risk
      factors: Tehran Lipid and Glucose Study.
AB  - BACKGROUND: Although fast food consumption has drastically increased in Iran in
      recent years; there is a paucity of data in relation to the association between
      fast food consumption, dietary intake, and cardiovascular risk factors. This
      study aims to determine fast food consumption status among young and middle-aged
      Iranian adults, and to assess its impact on dietary intake and cardiovascular
      disease (CVD) risk factors. METHODS: This cross-sectional population-based study
      was conducted on 1944 young and middle-aged adults (840 men and 1104 women), who
      participated in the Tehran Lipid and Glucose Study (2006-2008). We collected
      dietary data by using a validated 168 item, semi-quantitative food frequency
      questionnaire. Total fast food consumption was calculated by summing up weekly
      consumption of the most commonly consumed fast foods in Iran. RESULTS: Mean
      consumption of fast food was 161g/week (95% CI: 147-175) for young adults and 108
      g/week (95% CI: 101-115) for middle-aged adults. Mean dietary intakes of energy,
      fat, saturated fat, cholesterol, sodium, meat, and soft drinks increased
      significantly (P < 0.05), while carbohydrate and refined grain consumption
      decreased (P < 0.01) across tertiles of fast food in both age groups. In young
      adults, dietary energy density and protein intake increased significantly (P <
      0.01) where as intake of non-starchy vegetables and carotenoids decreased (P <
      0.05). In middle-aged adults dietary intakes of fiber, folate, calcium, and
      fruits significantly decreased across fast food tertiles (P < 0.05). After
      adjustment for confounders, there was an association between fast food
      consumption and body mass index (BMI; beta = 0.104; P < 0.01) and waist
      circumference (WC; beta= 0.083; P < 0.01) in young adults, and serum
      triglycerides (beta = 0.072; P < 0.05), high density lipoprotein cholesterol (HDL
      C; beta = -0.051; P < 0.05), and atherogenic index of plasma (beta = 0.056; P <
      0.05) in middle-aged adults. CONCLUSION: The results show that increased
      consumption of fast foods is associated with poor dietary intake and some of the
      CVD risk factors in Iranian adults.

PMID- 22642244
TI  - Expression of UBE2Q2, a putative member of the ubiquitin-conjugating enzyme
      family in pediatric acute lymphoblastic leukemia.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is a cancer of the white blood
      cells most commonly found in childhood with a peak incidence at 2-5 years of age.
      The ubiquitin degradation pathway facilitates degradation of damaged proteins and
      regulates the growth and stress response. This pathway is activated in various
      cancers, including ALL. It has been previously reported that the newly
      characterized human gene UBE2Q2, a putative member of the ubiquitin-conjugating
      enzyme family, is over-expressed in the tumor mass and invasive epithelium in
      head and neck squamous cell carcinoma and breast cancer. METHODS: Here, we have
      used quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to
      assess expression of the UBE2Q2 gene in bone marrow samples of 20 children with
      ALL. Whole blood samples of 20 normal children were used as control specimens. 
      RESULTS: RT-PCR revealed the expression of UBE2Q2 mRNA in 80% of the bone marrow
      samples from ALL patients as well as in 85% of leukemic normal peripheral blood
      cells. According to the results of quantitative RT-PCR, the levels of UBE2Q2 mRNA
      expression in the bone marrow cells of 11 out of the 20 children with ALL (55%)
      were significantly higher (> 2-47 fold) than those in blood cells of normal
      children. CONCLUSION: Our data suggest that the newly characterized human gene,
      UBE2Q2, may have implications for the pathogenesis of ALL and could be used for
      molecular diagnosis purposes in the future.

PMID- 22642245
TI  - An epidemiologic study of animal bites in Ilam Province, Iran.
AB  - BACKGROUND: In Iran, the number of stray dogs in cities and villages necessitates
      epidemiologic investigations. This study has undertaken an epidemiologic survey
      in Ilam, Iran with regard to animal bites during 1999-2009. METHODS: This was a
      cross-sectional descriptive study. The data due to animal bites was collected
      from patients and analyzed. RESULTS: The number of animal bites reported was
      4420, which included 3032 men (68.3%) and 398 women (31.7%). Most animal bites
      were reported in the 10-19 year-old (1172, 26%) age group. The feet were the most
      commonly attacked body part, which was reported in 3177 cases (71.8%). Most bites
      were from dogs (3942 cases, 89.15%). Of cases, 3419 (77.3%) resided in rural
      areas while 1001 (22.7%) were urban residents. The number of patients with
      incomplete vaccinations was 3596 (81.3%) compared to 824 (18.7%) completely
      vaccinated patients. CONCLUSION: The present study showed a high incidence of
      animal bites in Ilam, which necessitates the importance of rabies prevention and
      control. It is recommended that the sanitation authorities provide for and
      implement measures to determine beneficial ways to avoid and control rabies
      infection in this part of Iran.

PMID- 22642246
TI  - Mutational screening of ARX gene in Iranian families with X-linked intellectual
      disability.
AB  - BACKGROUND: Mutations in the human aristaless-related homeobox (ARX) gene are
      amongst the major causes of developmental and neurological disorders. They are
      responsible for a wide spectrum of phenotypes, including nonsyndromic X-linked
      intellectual disability (NS-XLID), and syndromic (XLIDS) forms such as X-linked
      lissencephaly with abnormal genitalia (XLAG), Partington syndrome (PRTS), and X
      linked infantile spasm syndrome (ISSX). The recurrent 24 bp duplication mutation,
      c.428_451dup(24 bp), is the most frequent ARX mutation, which accounts for ~40%
      of all cases reported to date. METHODS: We have screened the entire coding
      sequences of the ARX gene in 65 Iranian families with intellectual disabilities
      in order to obtain the relative prevalence of ARX mutations. At first these
      families were screened for the most recurrent mutation, the c.428_451dup(24 bp).
      For samples with negative results, single strand conformation polymorphism (SSCP)
      analysis was performed. RESULTS: We identified one family with the
      c.428_451dup(24 bp) duplication. Three shifts (one shift in exon 5 and two shifts
      in exon 4) were also identified among the total families. According to the
      results of the sequencing analysis, two shifts were not associated with any
      mutation and the other one was a c.1347C>T (p.G449G) substitution in exon 4.
      CONCLUSION: Hence, we suggest that molecular analysis of ARX mutations as a
      second cause of XLID should be considered as routine diagnostic procedure in any
      male who presents with either NS-XLID or XLIDS.

PMID- 22642247
TI  - ER-negative /PR-positive breast carcinomas or technical artifacts in
      immunohistochemistry?
AB  - BACKGROUND: Evaluation of estrogen (ER) and progesterone (PR) receptors is
      important in the management and prognosis of breast cancer patients.
      Immunohistochemistry (IHC) is currently the worldwide accepted methodology for
      detection of ER/PR receptors in breast carcinomas. However, technical artifacts
      may alter the results. Since most authorities believe that there are no true ER
      negative/PR-positive breast tumors, therefore we hypothesized that technical
      artifact in IHC might cause ER-negative/PR positive cases. METHODS: The clinical
      records of 2432 patients treated by surgery at six community hospitals for
      different histologic subtypes of breast carcinoma were reviewed. Among them, 43
      (1.8%) patients reported as ER-negative/PR-positive were re-evaluated in a
      reference laboratory. Expressions of ER and PR were evaluated by IHC on the same
      paraffin block used for the initial testing. RESULTS: The repeat study showed
      that of the 43 patients with the initial results of ER-negative/PR-positive, 24
      (55.8%) were ER-positive/PR-positive, 15 (34.9%) were ER-negative/PR-negative,
      and 4 (9.3%) were ER-positive/PR-negative. In none of the 43 cases were the
      initial results (ER-negative/PR-positive) confirmed. CONCLUSION: Technical
      artifacts in IHC may alter ER/PR results in breast carcinomas. The technical
      factors affecting steroid receptor IHC ought to be properly controlled to provide
      reliable results.

PMID- 22642248
TI  - Musculoskeletal disorders and ergonomic hazards among Iranian physicians.
AB  - BACKGROUND: The aim of this study was to determine the prevalence of
      musculoskeletal disorders (MSDs) and ergonomic hazards and their relationship
      among Iranian physicians who work in teaching hospitals. METHODS: A self
      administered questionnaire was provided to 405 physicians in four teaching
      hospitals. The questionnaire had three major parts: the first part gathered
      individual and work-related data, the second was a modified version of the
      Standardized Nordic questionnaire for musculoskeletal symptoms, and the last part
      evaluated the duration of exposure to ergonomic hazards at work. RESULTS: Knee
      pain (19.8%) was the most common complaint among physicians, followed by low back
      (15.1%) and neck pain (9.8%). A total of 169 physicians (41.7%) reported symptoms
      in at least one part of their bodies. Prolonged sitting, standing, and neck
      flexion were the most common reported ergonomic hazards among participants.
      Multiple logistic regression analysis reported statistically significant
      associations for the outcomes of knee pain and symptoms in any part of the body
      with the work-related factors of years of employment and work hours per shift.
      CONCLUSION: The prevalence of musculoskeletal complaints among physicians was
      low, less than other health care workers, but similar to those reported in the
      general population. These musculoskeletal complaints were, however, associated
      with traditional work-related and ergonomic factors.

PMID- 22642249
TI  - Corrected QT interval and QT dispersion in cirrhotic patients before and after
      liver transplantation.
AB  - BACKGROUND: Liver cirrhosis is associated with different types of
      electrophysiological changes, including QT prolongation, which may adversely
      affect long-term prognosis of these patients. The aim of this study is to
      evaluate the effect of orthotopic liver transplantation (LT) on corrected QT
      (QTc) interval and QT dispersion (QTd) in cirrhotic patients of various
      etiologies. METHODS: We enrolled 249 patients with end-stage liver disease
      between 2004 and 2009 at Shiraz Transplant Research Center, Shiraz, Iran. The QTc
      interval and QTd were measured by 12 lead ECGs for baseline and at 3 months after
      LT. Mean QTc interval and mean QTd were calculated. A QTc interval above 440 ms
      was considered abnormal. RESULTS: Within 3 months following surgery, 6 patients
      died. There were 105 patients (43.2%) with prolonged QTc before transplantation;
      in 91 (86.6%) patients, the mean QTc normalized after transplantation (baseline:
      490.9 +/- 45.74 ms; post-transplantation: 385 +/- 48.74 ms; P < 0.0001). Fourteen
      patients (13.3%) had evidence of some shortening of the QTc interval although the
      QTc remained above the upper limit of normal. Prolongation of the QTc interval in
      cirrhotic patients was independent of the etiology of cirrhosis. A normal QTc was
      seen in 138 patients (56.7%) before transplantation, of which 4 (2.9%) developed
      prolonged QTc after transplantation.  The mean QTd decreased significantly after
      transplantation (baseline: 30 +/- 20 ms; post-transplantation: 30 +/- 10 ms; P <
      0.0001). CONCLUSION: Many cirrhotic patients have prolonged QTc intervals before
      LT regardless of disease etiology. In the majority of patients this value returns
      to normal after LT, suggesting that liver cirrhosis has independent unfavorable,
      but reversible electrophysiological effects.

PMID- 22642250
TI  - Iranian and American health professionals working together to address health
      disparities in Mississippi Delta based on Iran's Health House model.

PMID- 22642251
TI  - Epileptic seizures in early-onset multiple sclerosis.
AB  - Early-onset multiple sclerosis (EOMS) is defined as the first presentation of
      symptoms in childhood (before the age of 16 years). EOMS occurs in about 0.4% to
      10.5% of multiple sclerosis (MS) patients. In this retrospective population-based
      study we aimed to describe the clinical/paraclinical details and frequency of
      epileptic seizures in Iranian EOMS patients registered with the Isfahan Multiple
      Sclerosis Society (IMSS) from April 2003 to July 2010. EOMS cases were extracted
      from the Isfahan total MS cohort and included 3522 patients. A total of 117 EOMS
      patients (19 males and 98 females) with a mean age at onset of 14.2 +/- 2.0 years
      (range: 7-16 years) were extracted from our database (3.3% of the total cohort).
      Of cases, ten (one male and nine females) had experienced at least two epileptic
      seizures, providing a crude prevalence of 8.5%. The frequency of epilepsy in EOMS
      patients (8.5%, 10/117) was significantly greater (P < 0.001) than that of non
      EOMS cohort (2.0%, 71/3405). Epileptic seizures occurred before MS onset in two
      patients, after MS onset in seven, and at MS onset in one as the presenting
      symptom of the disease. Our findings mostly indicate an excessive prevalence of
      epileptic seizures in Iranian EOMS patients (8.5%), which is higher than any
      other report concerning seizures or epileptic seizures in a large MS series.

PMID- 22642252
TI  - Tuberous sclerosis presented with  polycystic kidney disease and acute renal
      failure.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized
      by hamartomatous involvement of multiple organs such as the skin, central nervous
      system, kidneys, lungs, and heart. A linkage has been found with a locus on the
      long arm of chromosome 9 (9q34) and with a locus on the short arm of chromosome
      16 (16p13). TSC has a birth incidence of 1/6000. Children with TSC are almost
      universally born with normal kidneys, but cystic disease and angiomyolipomas
      develop with increasing age. Angiomyolipomas, renal cysts, and renal cell
      carcinoma are classical features of renal involvement in TSC. Renal complications
      are the most common cause of death in adult TSC patients, thus renal involvement
      has a crucial importance on the course of this disease. We present a 27-year-old
      patient previously diagnosed as tuberous sclerosis complex and referred with
      acute renal failure and polycystic kidney disease.

PMID- 22642253
TI  - Continuous sedation-analgesia delays diagnosis of compartment syndrome in a
      patient with intra-aortic balloon pump.
AB  - Compartment syndrome is a rare, devastating complication of coronary artery
      bypass grafting (CABG) and intra-aortic balloon pump (IABP). Prompt diagnosis is
      based on symptoms and signs and is paramount for limb rescue. This report
      describes a CABG patient with IABP in whom receiving continuous analgesia
      sedation obscured the symptoms of compartment syndrome.

PMID- 22642254
TI  - Photoclinic. Amyloid goiter.

PMID- 22642255
TI  - Values, perceived risks and benefits, and acceptability of nuclear energy.
AB  - We examined how personal values and perceptions of risks and benefits are
      associated with the acceptability of nuclear energy (NE). A theoretical model is
      tested in which beliefs about the risks and benefits of NE mediate the
      relationship between values and acceptability. The results showed that egoistic
      values are positively related to the perceived benefits and acceptability of NE.
      In contrast, altruistic and biospheric values were positively related to the
      perceived risks of NE. Although it has been argued that NE may help to combat
      climate change through lower CO(2)  emissions, these environmental benefits were
      not acknowledged by people with strong biospheric values. Furthermore, results
      confirmed that the more risks respondents perceived, the less they were inclined
      to accept NE. In contrast, the more a person believed that NE has beneficial
      consequences, the more acceptable NE was. Finally, as expected, perceived risks
      and benefits were found to partly mediate the relationship between personal
      values and acceptability. We discuss the theoretical and practical implications
      of these findings.

PMID- 22642256
TI  - Exposure to environmental toxins and the risk of sporadic motor neuron disease:
      an expanded Australian case-control study.
AB  - BACKGROUND AND PURPOSE: It remains unclear what role environmental toxins play in
      sporadic motor neuron disease (SMND) and its most common subtype, amyotrophic
      lateral sclerosis (SALS). Most previous studies of this issue have contained only
      small numbers of SMND cases. We sought to re-examine possible associations
      between toxins and SMND in a large Australian case-control study. METHODS:
      Questionnaire data were available from 787 patients with SMND (614 with SALS) and
      778 non-related controls. Individuals were asked whether they had been exposed to
      metals or chemicals/solvents at work or to herbicides/pesticides. Chi-square
      tests with odds ratios and 95% confidence intervals were calculated for
      responses, and significance levels were corrected for multiple testing. RESULTS:
      Men were more likely to acquire SALS if they worked with metals (OR = 1.95, 95%
      CI = 1.24-3.07) or chemicals/solvents (OR = 1.96, 95% CI = 1.46-2.61) or if they
      had been exposed to herbicides or pesticides (OR = 1.77, 95% CI = 1.30-2.39).
      Women who had worked with chemicals or solvents also appeared to be at increased
      risk of acquiring SALS (OR = 1.71, 95% CI = 1.22-2.40). CONCLUSIONS: These
      results support previous reports that exposures to metals or chemicals are
      associated with SMND. A suggested protocol for future multinational studies of
      environmental toxins and SMND is presented.

PMID- 22642257
TI  - Cell and gene therapy for genetic diseases: inherited disorders affecting the
      lung and those mimicking sudden infant death syndrome.
AB  - Some of the first human gene therapy trials targeted diseases of the lung and
      provided important information that will continue to help shape future trials.
      Here we describe both cell and gene therapies for lung diseases such as cystic
      fibrosis and alpha-1 antitrypsin disorder as well as fatty acid oxidation
      disorders that mimic sudden infant death syndrome (SIDS). Human clinical gene
      therapy trials for cystic fibrosis and alpha-1 antitrypsin have been performed
      using a variety of vectors including adenovirus, adeno-associated virus, and
      nonviral vectors. No human clinical gene therapy trials have been performed for
      disorders of fatty acid oxidation; however, important proof-of-principle studies
      have been completed for multiple fatty acid oxidation disorders. Important
      achievements have been made and have yet to come for cell and gene therapies for
      disorders of the lung and those mimicking SIDS.

PMID- 22642258
TI  - Selective estrogen receptor modulator (SERM) lasofoxifene forms reactive quinones
      similar to estradiol.
AB  - The bioactivation of both endogenous and equine estrogens to electrophilic
      quinoid metabolites has been postulated as a contributing factor in carcinogenic
      initiation and/or promotion in hormone sensitive tissues. Bearing structural
      resemblance to estrogens, extensive studies have shown that many selective
      estrogen receptor modulators (SERMs) are subject to similar bioactivation
      pathways. Lasofoxifene (LAS), a third generation SERM which has completed phase
      III clinical trials for the prevention and treatment of osteoporosis, is
      currently approved in the European Union for this indication. Previously, Prakash
      et al. (Drug Metab. Dispos. (2008) 36, 1218-1226) reported that similar to
      estradiol, two catechol regioisomers of LAS are formed as primary oxidative
      metabolites, accounting for roughly half of the total LAS metabolism. However,
      the potential for further oxidation of these catechols to electrophilic o
      quinones has not been reported. In the present study, LAS was synthesized and its
      oxidative metabolism investigated in vitro under various conditions. Incubation
      of LAS with tyrosinase, human liver microsomes, or rat liver microsomes in the
      presence of GSH as a trapping reagent resulted in the formation of two mono-GSH
      and two di-GSH catechol conjugates which were characterized by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Similar conjugates were also
      detected in incubations with P450 3A4, P450 2D6, and P450 1B1 supersomes.
      Interestingly, these conjugates were also detected as major metabolites when
      compared to competing detoxification pathways such as glucuronidation and
      methylation. The 7-hydroxylasofoxifene (7-OHLAS) catechol regioisomer was also
      synthesized and oxidized either chemically or enzymatically to an o-quinone that
      was shown to form depurinating adducts with DNA. Collectively, these data show
      that analogous to estrogens, LAS is oxidized to catechols and o-quinones which
      could potentially contribute to in vivo toxicity for this SERM.

PMID- 22642259
TI  - Design, synthesis, and pharmacological evaluation of glutamate carboxypeptidase
      II (GCPII) inhibitors based on thioalkylbenzoic acid scaffolds.
AB  - A series of thiol-based glutamate carboxypeptidase II (GCPII) inhibitors have
      been synthesized with either a 3-(mercaptomethyl)benzoic acid or 2-(2
      mercaptoethyl)benzoic acid scaffold. Potent inhibitors were identified from each
      of the two scaffolds with IC(50) values in the single-digit nanomolar range,
      including 2-(3-carboxybenzyloxy)-5-(mercaptomethyl)benzoic acid 27c and 3-(2
      mercaptoethyl)biphenyl-2,3'-dicarboxylic acid 35c. Compound 35c was found to be
      metabolically stable and selective over a number of targets related to glutamate
      mediated neurotransmission. Furthermore, compound 35c was found to be orally
      available in rats and exhibited efficacy in an animal model of neuropathic pain
      following oral administration.

PMID- 22642261
TI  - Ten years later. Results from a prospective single-centre clinical study on 121
      oxidized (TiUniteTM) Branemark implants in 46 patients.
AB  - BACKGROUND: Concerns have been raised that use of surface-modified implants may
      result in peri-implant infection and marked marginal bone loss over time.
      PURPOSE: The aim of this prospective study was to evaluate the survival rate,
      marginal bone, and soft tissue conditions at surface-modified titanium dental
      implants after 10 years of function. MATERIAL AND METHODS: Forty-six totally and
      partially edentulous patients were provided with 121 Branemark oxidized implants
      (TiUniteTM, Nobel Biocare AB, Gothenburg, Sweden). Twenty-four (20%) implants
      were immediate loaded and 97 (80%) were placed using a two-stage procedure. A
      total of 22 single, 23 partial, and 7 total restorations were delivered. Clinical
      and radiographic checkups were carried out after 3, 6, 12 months, and thereafter
      annually up to 10 years. At these occasions, oral hygiene was evaluated and peri
      implant mucosa examined by probing. If needed, patients were enrolled in an
      individual program for hygiene controls and professional cleaning. Marginal bone
      loss was evaluated in intraoral radiographs taken at baseline and after 1, 5, and
      10 years of function. RESULTS: One (0.8%) implant failed after 8 years giving a
      Survival Rate (SR) of 99.2% after 10 years. A total of 11 sites (9.2%) showed
      bleeding on probing (BP) at the 10th annual checkup. The mean marginal bone loss
      was 0.7 +/- 1.35 mm based on 106 readable pairs of radiographs from baseline and
      from the 10th annual examination. Twelve (11.3%) implants showed more than 2 mm
      bone loss, and five (4.7%) showed more than 3 mm of bone loss after 10 years. For
      the latter, all patients were smokers and had poor or acceptable oral hygiene.
      All five implants with >3 mm bone loss showed BP and two (1.9%) showed
      suppuration from the pocket. For the remaining seven implants with more than 2 mm
      bone loss, no correlation to smoking, oral hygiene, bleeding, or pus could be
      seen. Time/marginal bone level plots of the 12 implants with more than 2 mm bone
      loss after 10 years, showed minor changes from the first annual checkup except
      for the two infected implants. CONCLUSIONS: It is concluded that good long-term
      clinical outcomes can be obtained with oxidized titanium dental implants. Only
      1.9% of examined implants showed significant marginal bone loss together with
      bleeding and suppuration after 10 years of function.

PMID- 22642260
TI  - Potential factors influencing the development of thrombocytopenia and consumptive
      coagulopathy after genetically modified pig liver xenotransplantation.
AB  - Upregulation of tissue factor (TF) expression on activated donor endothelial
      cells (ECs) triggered by the immune response (IR) has been considered the main
      initiator of consumptive coagulopathy (CC). In this study, we aimed to identify
      potential factors in the development of thrombocytopenia and CC after genetically
      engineered pig liver transplantation in baboons. Baboons received a liver from
      either an alpha1,3-galactosyltransferase gene-knockout (GTKO) pig (n = 1) or a
      GTKO pig transgenic for CD46 (n = 5) with immunosuppressive therapy. TF exposure
      on recipient platelets and peripheral blood mononuclear cell (PBMCs), activation
      of donor ECs, platelet and EC microparticles, and the IR were monitored. Profound
      thrombocytopenia and thrombin formation occurred within minutes of liver
      reperfusion. Within 2 h, circulating platelets and PBMCs expressed functional TF,
      with evidence of aggregation in the graft. Porcine ECs were negative for
      expression of P- and E-selectin, CD106, and TF. The measurable IR was minimal,
      and the severity and rapidity of thrombocytopenia were not alleviated by prior
      manipulation of the IR. We suggest that the development of thrombocytopenia/CC
      may be associated with TF exposure on recipient platelets and PBMCs (but possibly
      not with activation of donor ECs). Recipient TF appears to initiate
      thrombocytopenia/CC by a mechanism that may be independent of the IR.

PMID- 22642262
TI  - Coherent fifth-order visible-infrared spectroscopies: ultrafast nonequilibrium
      vibrational dynamics in solution.
AB  - Obtaining a detailed description of photochemical reactions in solution requires
      measuring time-evolving structural dynamics of transient chemical species on
      ultrafast time scales. Time-resolved vibrational spectroscopies are sensitive
      probes of molecular structure and dynamics in solution. In this work, we develop
      doubly resonant fifth-order nonlinear visible-infrared spectroscopies to probe
      nonequilibrium vibrational dynamics among coupled high-frequency vibrations
      during an ultrafast charge transfer process using a heterodyne detection scheme.
      The method enables the simultaneous collection of third- and fifth-order signals,
      which respectively measure vibrational dynamics occurring on electronic ground
      and excited states on a femtosecond time scale. Our data collection and analysis
      strategy allows transient dispersed vibrational echo (t-DVE) and dispersed pump
      probe (t-DPP) spectra to be extracted as a function of electronic and vibrational
      population periods with high signal-to-noise ratio (S/N > 25). We discuss how
      fifth-order experiments can measure (i) time-dependent anharmonic vibrational
      couplings, (ii) nonequilibrium frequency-frequency correlation functions, (iii)
      incoherent and coherent vibrational relaxation and transfer dynamics, and (iv)
      coherent vibrational and electronic (vibronic) coupling as a function of a
      photochemical reaction.

PMID- 22642263
TI  - Mycoheterotrophic germination of Pyrola asarifolia dust seeds reveals
      convergences with germination in orchids.
AB  - Dust seeds that germinate by obtaining nutrients from symbiotic fungi have
      evolved independently in orchids and 11 other plant lineages. The fungi involved
      in this 'mycoheterotrophic' germination have been identified in some orchids and
      non-photosynthetic Ericaceae, and proved identical to mycorrhizal fungi of adult
      plants. We investigated a third lineage, the Pyroleae, chlorophyllous Ericaceae
      species whose partial mycoheterotrophy at adulthood has recently attracted much
      attention. We observed experimental Pyrola asarifolia germination at four
      Japanese sites and investigated the germination pattern and symbiotic fungi,
      which we compared to mycorrhizal fungi of adult plants. Adult P. asarifolia, like
      other Pyroleae, associated with diverse fungal species that were a subset of
      those mycorrhizal on surrounding trees. Conversely, seedlings specifically
      associated with a lineage of Sebacinales clade B (endophytic Basidiomycetes)
      revealed an intriguing evolutionary convergence with orchids, some of which also
      germinate with Sebacinales clade B. Congruently, seedlings clustered spatially
      together, but not with adults. This unexpected transition in specificity and
      ecology of partners could support the developmental transition from full to
      partial mycoheterotrophy, but probably challenges survival and distribution
      during development. We discuss the physiological and ecological traits that
      predisposed to the repeated recruitment of Sebacinales clade B for dust seed
      germination.

PMID- 22642264
TI  - Permanent genetic resources added to Molecular Ecology Resources Database 1
      February 2012 - 31 March 2012.
AB  - This article documents the addition of 171 microsatellite marker loci and 27
      pairs of single nucleotide polymorphism (SNP) sequencing primers to the Molecular
      Ecology Resources Database. Loci were developed for the following species: Bombus
      pauloensis, Cephalorhynchus heavisidii, Cercospora sojina, Harpyhaliaetus
      coronatus, Hordeum vulgare, Lachnolaimus maximus, Oceanodroma monteiroi, Puccinia
      striiformis f. sp. tritici, Rhea americana, Salmo salar, Salmo trutta,
      Schistocephalus solidus, Sousa plumbea and Tursiops aduncus. These loci were
      cross-tested on the following species: Aquila heliaca, Bulweria bulwerii, Buteo
      buteo, Buteo swainsoni, Falco rusticolus, Haliaeetus albicilla, Halobaena
      caerulea, Hieraaetus fasciatus, Oceanodroma castro, Puccinia graminis f. sp.
      Tritici, Puccinia triticina, Rhea pennata and Schistocephalus pungitii. This
      article also documents the addition of 27 sequencing primer pairs for Puffinus
      baroli and Bulweria bulwerii and cross-testing of these loci in Oceanodroma
      castro, Pelagodroma marina, Pelecanoides georgicus, Pelecanoides urinatrix,
      Thalassarche chrysostoma and Thalassarche melanophrys.

PMID- 22642265
TI  - Impact of smoking status at diagnosis on disease recurrence and death in upper
      tract urothelial carcinoma.
AB  - Cigarette smoking is the leading cause of urothelial carcinoma; however, the
      impact of smoking on outcomes after surgery for upper tract urothelial carcinoma
      is unknown. One study suggests that patients with a smoking history have an
      increased risk of recurrence in the bladder compared with never smokers but these
      patients did not differ with respect to time to pelvic recurrence or distant
      metastasis. We subdivided smokers into current and former smokers and performed
      multivariate analyses that showed that smoking status was not an independent
      predictor of recurrence when traditional prognostic factors were taken into
      account. In addition, competing risks analyses showed that although current
      smoking did not increase the risk of recurrence, it imparted a significant risk
      of dying compared with former and never smoking. OBJECTIVE: To evaluate the
      impact of smoking exposure on oncological outcomes in patients with upper tract
      urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU).
      MATERIALS AND METHODS: Patient and disease characteristics from 288 patients with
      UTUC treated with RNU between 1995 and 2008 were collected from a prospectively
      maintained database at the Memorial Sloan-Kettering Cancer Center. Disease
      recurrence was defined as distant metastases, or local failure in the operative
      site or regional nodes. Factors associated with recurrence and death were
      determined. RESULTS: The prevalence of current, former and never smoking at
      diagnosis was 19.1%, 55.2%, and 25.7%, respectively. 71.0% of patients reported a
      >=20 pack-year smoking history. With a median follow-up of 4.02 years, disease
      recurrence occurred in 27% (n = 79) of patients and 41% (n = 117) died during
      follow-up. While age at diagnosis, American Society of Anesthesiologists score,
      advanced stage, nodal involvement and high grade adversely affected recurrence
      free survival, smoking status was not associated with risk of recurrence or death
      in multivariate analysis (P = 0.60). Multivariate competing risks regression
      showed that current smokers faced a significantly higher risk of death than never
      smokers (hazard ratio 3.64, 95% confidence interval 1.59-8.34). CONCLUSIONS:
      While smoking status at diagnosis and cumulative smoking exposure were not
      associated with UTUC recurrence, our findings highlight the substantial risk of
      death in patients with UTUC who are active smokers. Treatment plans to promote
      smoking cessation are recommended for these patients.

PMID- 22642266
TI  - Workplace support, discrimination, and person-organization fit: tests of the
      theory of work adjustment with LGB individuals.
AB  - The present study explored the links of 2 workplace contextual variables-
      perceptions of workplace heterosexist discrimination and lesbian, gay, and
      bisexual (LGB)-supportive climates--with job satisfaction and turnover intentions
      in a sample of LGB employees. An extension of the theory of work adjustment (TWA)
      was used as the conceptual framework for the study; as such, perceived person
      organization (P-O) fit was tested as a mediator of the relations between the
      workplace contextual variables and job outcomes. Data were analyzed from 326 LGB
      employees. Zero-order correlations indicated that perceptions of workplace
      heterosexist discrimination and LGB-supportive climates were correlated in
      expected directions with P-O fit, job satisfaction, and turnover intentions.
      Structural equation modeling (SEM) was used to compare multiple alternative
      measurement models evaluating the discriminant validity of the 2 workplace
      contextual variables relative to one another, and the 3 TWA job variables
      relative to one another; SEM was also used to test the hypothesized mediation
      model. Comparisons of multiple alternative measurement models supported the
      construct distinctiveness of the variables of interest. The test of the
      hypothesized structural model revealed that only LGB-supportive climates (and not
      workplace heterosexist discrimination) had a unique direct positive link with P-O
      fit and, through the mediating role of P-O fit, had significant indirect positive
      and negative relations with job satisfaction and turnover intentions,
      respectively. Moreover, P-O fit had a significant indirect negative link with
      turnover intentions through job satisfaction.

PMID- 22642267
TI  - Disability research in counseling psychology journals: a 20-year content
      analysis.
AB  - We conducted an exploratory content analysis of disability research in 5 major
      counseling psychology journals between 1990 and 2010. The goal was to review the
      counseling psychology literature to better understand the prevalence of
      disability research, identify research methods most often conducted, and
      elucidate the types of concerns most studied. We searched 5 journals (Journal of
      Counseling & Development, Journal of Counseling Psychology, The Counseling
      Psychologist, Journal of Multicultural Counseling and Development, and Cultural
      Diversity and Ethnic Minority Psychology) using keywords derived from disability
      terms defined by the Individuals With Disabilities Education Improvement Act of
      2004 (IDEA). Articles were categorized by methodology and disability category
      examined. We found that disability research continues to comprise an extremely
      small amount (from less than 1% to 2.7%) of the counseling psychology literature,
      with the frequency of articles plateauing in recent years. The research design of
      articles published has changed, with an increased number of empirical articles
      and a decrease in literature reviews. We conclude by calling for increased
      empirical investigation of disability among journals specific to counseling
      psychology to recognize disability as an important aspect of diversity within the
      field.

PMID- 22642268
TI  - Profiles of acculturative adjustment patterns among Chinese international
      students.
AB  - This is the first study to empirically identify distinct acculturative adjustment
      patterns of new international students over their first 3 semesters in the United
      States. The sample consisted of 507 Chinese international students studying in
      the United States. Using psychological distress as an indicator of acculturative
      adjustment, measured over 4 time points (prearrival, first semester, second
      semester, and third semester), 4 distinct groups of student adjustment
      trajectories emerged: (a) a group exhibiting high levels of psychological
      distress across each time point (consistently distressed; 10%), (b) a group with
      decreasing psychological distress scores from Time 1 to Time 2 (relieved; 14%),
      (c), those with a sharp peak in psychological distress at Time 2 and Time 3
      (culture-shocked; 11%), and (d) a group with relatively consistent low
      psychological distress scores (well-adjusted; 65%). Moreover, significant
      predictors of a better acculturative adjustment pattern included having higher
      self-esteem, positive problem-solving appraisal, and lower maladaptive
      perfectionism prior to the acculturation process. In addition, during the first
      semester of studying in the United States, having a balanced array of social
      support and using acceptance, reframing, and striving as coping strategies were
      associated with a better cross-cultural transition. Practical implications and
      future directions were also discussed.

PMID- 22642270
TI  - The use of clinical decision-support tools to facilitate geriatric education.
AB  - Innovative methods are needed to incorporate effective geriatric education into
      internal medicine residency programs. The purpose of this report is to describe
      the development and use of clinical decision-support (CDS) tools to facilitate
      geriatric education and improve the care delivered to older adults in an academic
      internal medicine residency ambulatory care clinic. Starting in 2009, CDS tools
      were implemented as a major strategy of an initiative to improve resident
      physician clinical competencies in geriatrics and improve the quality of care and
      quality of life of older adults. These tools, designed to improve resident
      assessment and action for each of three educational modules (falls, vision, and
      dementia) were embedded within the ambulatory electronic medical record (EMR) and
      provided a method of point-of-care training to residents caring for older adults.
      One hundred internal medicine residents supervised by 17 general internal
      medicine faculty members participated. Data regarding CDS use and associated
      outcomes were recorded and extracted from the ambulatory clinic EMR. Residents
      screened between 67% and 88% of eligible patients using CDS algorithms; rates of
      additional assessment and referral or further examination reflected the
      prevalence of the condition in the patient population. Although further
      development may be necessary, CDS tools are a promising modality to supplement
      geriatric postgraduate education while simultaneously improving patient care.

PMID- 22642269
TI  - Development of a Grp94 inhibitor.
AB  - Heat shock protein 90 (Hsp90) represents a promising therapeutic target for the
      treatment of cancer and other diseases. Unfortunately, results from clinical
      trials have been disappointing as off-target effects and toxicities have been
      observed. These detriments may be a consequence of pan-Hsp90 inhibition, as all
      clinically evaluated Hsp90 inhibitors simultaneously disrupt all four human Hsp90
      isoforms. Using a structure-based approach, we designed an inhibitor of Grp94,
      the ER-resident Hsp90. The effect manifested by compound 2 on several Grp94 and
      Hsp90alpha/beta (cytosolic isoforms) clients were investigated. Compound 2
      prevented intracellular trafficking of the Toll receptor, inhibited the secretion
      of IGF-II, affected the conformation of Grp94, and suppressed Drosophila larval
      growth, all Grp94-dependent processes. In contrast, compound 2 had no effect on
      cell viability or cytosolic Hsp90alpha/beta client proteins at similar
      concentrations. The design, synthesis, and evaluation of 2 are described herein.

PMID- 22642271
TI  - Determinants of infant formula use and relation with growth in the first 4
      months.
AB  - The wide variety of infant formula available on the market can be confusing for
      parents and physicians. We aimed to determine associations between predominant
      type of formula used from birth to 4 months and parental and child
      characteristics and type of physician consulted, and then to describe relations
      between type of formula used and growth. Our analyses included 1349 infants from
      the EDEN mother-child cohort. Infant's feeding mode and type of formula used were
      assessed at 4 months by maternal self-report. Infant's weight and height from
      birth to 4 months, measured in routine follow-up, were documented by health
      professionals in the infant's personal health record. Anthropometric z-scores
      were calculated by using World Health Organization growth standards. Multinomial
      logistic regression was used to identify factors associated with the type of
      formula predominantly used; relations with growth were analysed by linear
      regressions. Partially hydrolysed formulas were more likely to be used by
      primiparous women (P < 0.001), those breastfeeding longer (P < 0.001) and for
      infants with family history of allergies (P = 0.002). Thickened formulas were
      more often used by mothers returning to employment in the first 4 months (P =
      0.05) and breastfeeding shortly (P < 0.001). No significant relation was found
      between infant's growth and type of formula (P > 0.20). Infants breastfed shorter
      showed higher weight-for-age (P < 0.001) and length-for-age (P = 0.001) z-score
      changes between birth and 4 months. The use of a specific type of infant formula
      seems to be mainly related to parental characteristics. Infant's growth in the
      first 4 months is related to other factors than to the type of formula used.

PMID- 22642273
TI  - Chronic myelogenous leukemia.

PMID- 22642272
TI  - Characterization and dioxygen reactivity of a new series of coordinatively
      unsaturated thiolate-ligated manganese(II) complexes.
AB  - The synthesis, structural, and spectroscopic characterization of four new
      coordinatively unsaturated mononuclear thiolate-ligated manganese(II) complexes
      ([Mn(II)(S(Me2)N(4)(6-Me-DPEN))](BF(4)) (1), [Mn(II)(S(Me2)N(4)(6-Me
      DPPN))](BPh(4)).MeCN (3), [Mn(II)(S(Me2)N(4)(2-QuinoPN))](PF(6)).MeCN.Et(2)O (4),
      and [Mn(II)(S(Me2)N(4)(6-H-DPEN)(MeOH)](BPh(4)) (5)) is described, along with
      their magnetic, redox, and reactivity properties. These complexes are
      structurally related to recently reported [Mn(II)(S(Me2)N(4)(2-QuinoEN))](PF(6))
      (2) (Coggins, M. K.; Kovacs, J. A. J. Am. Chem. Soc.2011, 133, 12470). Dioxygen
      addition to complexes 1-5 is shown to result in the formation of five new rare
      examples of Mn(III) dimers containing a single, unsupported oxo bridge:
      [Mn(III)(S(Me2)N(4)(6-Me-DPEN)](2)-(MU-O)(BF(4))(2).2MeOH (6),
      [Mn(III)(S(Me2)N(4)(QuinoEN)](2)-(MU-O)(PF(6))(2).Et(2)O (7),
      [Mn(III)(S(Me2)N(4)(6-Me-DPPN)](2)-(MU-O)(BPh(4))(2) (8),
      [Mn(III)(S(Me2)N(4)(QuinoPN)](2)-(MU-O)(BPh(4))(2) (9), and [Mn(III)(S(Me2)N(4)(6
      H-DPEN)](2)-(MU-O)(PF(6))(2).2MeCN (10). Labeling studies show that the oxo atom
      is derived from (18)O(2). Ligand modifications, involving either the insertion of
      a methylene into the backbone or the placement of an ortho substituent on the N
      heterocyclic amine, are shown to noticeably modulate the magnetic and reactivity
      properties. Fits to solid-state magnetic susceptibility data show that the
      Mn(III) ions of MU-oxo dimers 6-10 are moderately antiferromagnetically coupled,
      with coupling constants (2J) that fall within the expected range. Metastable
      intermediates, which ultimately convert to MU-oxo bridged 6 and 7, are observed
      in low-temperature reactions between 1 and 2 and dioxygen. Complexes 3-5, on the
      other hand, do not form observable intermediates, thus illustrating the effect
      that relatively minor ligand modifications have upon the stability of metastable
      dioxygen-derived species.

PMID- 22642274
TI  - Is Provenge Angst a symbol or symptom of the times?

PMID- 22642275
TI  - Testing for ALK-positive NSCLC.

PMID- 22642276
TI  - Forging a pathway to quality cancer care.

PMID- 22642277
TI  - Prostate cancer.

PMID- 22642278
TI  - Value-based reimbursement in oncology.

PMID- 22642279
TI  - Long-term breast cancer patient follow-up care.

PMID- 22642280
TI  - Myeloproliferative disorders and myelofibrosis.

PMID- 22642281
TI  - BRCA1/2 genetic testing found cost-effective in current era.

PMID- 22642282
TI  - Trends in the 2012 Eisai Oncology Digest: patient demographics and cancer
      treatment goals.

PMID- 22642284
TI  - Cancer care value-learning from others.

PMID- 22642285
TI  - On the horizon for multiple myeloma.
AB  - Treatment of multiple myeloma (MM) remains highly individualized, with multiple
      factors that play a role in determining the best course of therapy. Patient
      specific criteria such as age of onset, whether the patient is symptomatic at the
      time of diagnosis, and any detected high-risk cytogenic abnormalities are all
      considerations when selecting a regimen. Newer agents such as bortezomib and
      lenalidomide in combination with low-dose steroids have replaced more toxic
      chemotherapeutic regimens for primary induction and have led to significant
      increases in progression-free survival. Depending on duration of response prior
      to relapse, patients may be rechallenged with the same regimen, switched to an
      alternative, or may undergo hematopoietic cell transplant (HCT), which remains a
      highly effective treatment option for patients who are candidates. However, the
      cost of transplantation remains high and some patients may require a second
      transplantation if the initial response is incomplete. With the availability of
      newer agents for salvage therapies in refractory or relapsed patients, the
      reliance on HCT may decrease, potentially lowering healthcare costs. In addition,
      the availability of orally active agents may decrease the need for outpatient
      infusions, thus decreasing the overall costs associated with treatment and
      improving patient satisfaction. Finally, combination regimens that use lower
      doses may prove to be less toxic as well as more effective. Even though MM only
      accounts for approximately 1% of all cancers in the United States, with 75
      million "baby boomers" now reaching the median age of diagnosis, the increased
      number of cases could have a substantial impact on healthcare costs.

PMID- 22642286
TI  - Oncology hit hard by SGR debacle. An interview with Allen S. Lichter.

PMID- 22642287
TI  - The effect of injury severity on behavior: a phenotypic study of cognitive and
      emotional deficits after mild, moderate, and severe controlled cortical impact
      injury in mice.
AB  - Traumatic brain injury (TBI) can cause a broad array of behavioral problems
      including cognitive and emotional deficits. Human studies comparing
      neurobehavioral outcomes after TBI suggest that cognitive impairments increase
      with injury severity, but emotional problems such as anxiety and depression do
      not. To determine whether cognitive and emotional impairments increase as a
      function of injury severity we exposed mice to sham, mild, moderate, or severe
      controlled cortical impact (CCI) and evaluated performance on a variety of
      neurobehavioral tests in the same animals before assessing lesion volume as a
      histological measure of injury severity. Increasing cortical impact depth
      successfully produced lesions of increasing severity in our model. We found that
      cognitive impairments in the Morris water maze increased with injury severity, as
      did the degree of contralateral torso flexion, a measure of unilateral striatal
      damage. TBI also caused deficits in emotional behavior as quantified in the
      forced swim test, elevated-plus maze, and prepulse inhibition of acoustic
      startle, but these deficits were not dependent on injury severity. Stepwise
      regression analyses revealed that Morris water maze performance and torso flexion
      predicted the majority of the variability in lesion volume. In summary, we find
      that cognitive deficits increase in relation to injury severity, but emotional
      deficits do not. Our data suggest that the threshold for emotional changes after
      experimental TBI is low, with no variation in behavioral deficits seen between
      mild and severe brain injury.

PMID- 22642288
TI  - Comparison of acute oxidative stress on rat lung induced by nano and fine-scale,
      soluble and insoluble metal oxide particles: NiO and TiO2.
AB  - The aim of the present study is to understand the association between metal ion
      release from nickel oxide (NiO) nanoparticles and induction of oxidative stress
      in the lung. NiO nanoparticles have cytotoxic activity through nickel ion release
      and subsequent oxidative stress. However, the interaction of oxidative stress and
      nickel ion release in vivo is still unclear. In the present study, we examined
      the effect of metal ion release on oxidative stress induced by NiO nanoparticles.
      Additionally, nano and fine TiO(2) particles as insoluble particles were also
      examined. Rat lung was exposed to NiO and TiO(2) nanoparticles by intratracheal
      instillation. The NiO nanoparticles released Ni(2+) in dispersion.
      Bronchoalveolar lavage fluid (BALF) was collected at 1, 24, 72 h and 1 week after
      instillation. The lactate dehydrogenase (LDH) and HO-1 levels were elevated at 24
      and 72 h after instillation in the animals exposed to the NiO nanoparticles. On
      the other hand, total hydroxyoctadecadienoic acid (tHODE), which is an oxidative
      product of linoleic acid, as well as SP-D and alpha-tochopherol levels were
      increased at 72 h and 1 week after instillation. Fine NiO particles, and nano and
      fine TiO(2) particles did not show lung injury or oxidative stress from 1 h to 1
      week after instillation. These results suggest that Ni(2+) release is involved in
      the induction of oxidative stress by NiO nanoparticles in the lung. Ni(2+)
      release from NiO nanoparticles is an important factor inoxidative stress-related
      toxicity, not only in vitro but also in vivo.

PMID- 22642289
TI  - Modelling of individual subject ozone exposure response kinetics.
AB  - CONTEXT: A better understanding of individual subject ozone (O(3)) exposure
      response kinetics will provide insight into how to improve models used in the
      risk assessment of ambient ozone exposure. OBJECTIVE: To develop a simple two
      compartment exposure-response model that describes individual subject decrements
      in forced expiratory volume in one second (FEV(1)) induced by the acute
      inhalation of O(3) lasting up to 8 h. METHODS: FEV(1) measurements of 220
      subjects who participated in 14 previously completed studies were fit to the
      model using both particle swarm and nonlinear least squares optimization
      techniques to identify three subject-specific coefficients producing minimum
      "global" and local errors, respectively. Observed and predicted decrements in
      FEV(1) of the 220 subjects were used for validation of the model. Further
      validation was provided by comparing the observed O(3)-induced FEV(1) decrements
      in an additional eight studies with predicted values obtained using model
      coefficients estimated from the 220 subjects used in cross validation. RESULTS:
      Overall the individual subject measured and modeled FEV(1) decrements were highly
      correlated (mean R(2) of 0.69 +/- 0.24). In addition, it was shown that a matrix
      of individual subject model coefficients can be used to predict the mean and
      variance of group decrements in FEV(1). CONCLUSION: This modeling approach
      provides insight into individual subject O(3) exposure response kinetics and
      provides a potential starting point for improving the risk assessment of
      environmental O(3) exposure.

PMID- 22642290
TI  - Are airborne refractory ceramic fibers similar to asbestos in their
      carcinogenicity?
AB  - BACKGROUND: Animal studies on refractory ceramic fiber (RCF) have led to the
      suggestion that RCF might resemble asbestos in carcinogenicity. Human data are
      available to test this hypothesis. METHODS: We compared the occurrence of lung
      cancer and mesothelioma in 605 men engaged in the manufacture of RCF and followed
      since 1987 to cancer rates that would have been anticipated if airborne RCF were
      carcinogenic to the same degree as are crocidolite, amosite or chrysotile
      asbestos. We integrated the results of workplace exposure monitoring with
      mortality follow-up using formulas presented by Hodgson and Darnton (2000) to
      estimate hypothesized risks under different asbestos scenarios. RESULTS: During
      15,281 person-years of observation, there were 12 deaths from lung cancer.
      General population rates predicted 11.8 cases expected for an observed/expected
      (O/E) ratio of 1.0. Anticipated numbers of deaths from lung cancer under
      hypotheses of carcinogenicity similar to that of amphiboles and chrysotile were
      62 and 17, allowing for rejection of amphibole-like effects (p < 10(-5)) but not
      chrysotile-like carcinogenicity (p = 0.15). There were no cases of mesothelioma,
      as compared to 4.9 anticipated under a crocidolite-like hypothesis (p = 0.007 to
      reject), 1.0 for amosite (p = 0.38) and 0.05 for chrysotile (p = 0.95).
      CONCLUSION: There was no increase in lung cancer or mesothelioma in these workers
      exposed to RCF. If the cohort had the same exposure to crocidolite asbestos the
      number of lung cancer and mesothelioma cases would have been significantly
      greater than observed. The data do not yet permit a similar conclusion with
      respect to chrysotile asbestos.

PMID- 22642291
TI  - Monitoring exposure to airborne ultrafine particles in Lisbon, Portugal.
AB  - The aim of this study is to contribute to the assessment of exposure levels of
      ultrafine particles (UFP) in the urban environment of Lisbon, Portugal, due to
      automobile traffic, by monitoring lung-deposited alveolar surface area (resulting
      from exposure to UFP) in a major avenue leading to the town centre during late
      Spring, as well as in indoor buildings facing it. This study revealed
      differentiated patterns for week days and weekends, consistent with PM(2.5) and
      PM(10) patterns currently monitored by air quality stations in Lisbon. The
      observed ultrafine particulate levels could be directly related with the fluxes
      of automobile traffic. During a typical week, UFP alveolar deposited surface area
      varied between 35.0 and 89.2 um(2)/cm(3), which is comparable with levels
      reported for other towns such in Germany and United States. The measured values
      allowed the determination of the number of UFP per cm(3), which are comparable to
      levels reported for Madrid and Brisbane. In what concerns outdoor/indoor levels,
      we observed higher levels (32-63%) outdoor, which is somewhat lower than levels
      observed in houses in Ontario.

PMID- 22642292
TI  - Clinical presentation and management in acute toluene intoxication: a case
      series.
AB  - CONTEXT: Toluene inhalation is a common form of drug abuse throughout the world.
      Acute toluene toxicity causes neurological changes as well as various metabolic
      alterations. Hypokalemic paralysis and renal failure are life-threatening
      complications. OBJECTIVE: To identify the clinical and metabolic alterations
      associated with toluene intoxication. MATERIALS AND METHODS: We retrospectively
      analyzed the records of 22 patients that were admitted to a single center's
      emergency department from 2006 to 2012 with clinical and metabolic alterations
      due to toluene inhalation. RESULTS: Of the 22 patients, 77% were male and mean
      age was 23.5 years (range: 17-30). The main clinical presentation was weakness
      associated to severe hypokalemia. Severe metabolic acidosis was found in 20
      patients. Renal tubular acidosis was diagnosed in five patients. The patients
      responded to supportive measures and aggressive potassium repletion. Prognosis
      was generally good. CONCLUSION: Toluene inhalation is associated with various
      severe metabolic alterations. Treatment guidelines are needed considering the
      frequency of toluene inhalation in the population.

PMID- 22642293
TI  - Repeated inhalation of crack-cocaine affects spermatogenesis in young and adult
      mice.
AB  - To investigate the effects of repeated crack-cocaine inhalation on
      spermatogenesis of pubertal and mature Balb/c mice, ten young (Y(ex)) and ten
      adult (A(ex)) Balb/c mice were exposed to the smoke from 5 g of crack with 57.7%
      of pure cocaine in an inhalation chamber, 5 days/week for 2 months. The young
      (Y(c)) and adult (A(c)) control animals (n = 10) were kept in a specially built
      and controlled animal house facility. The morphologic analysis of both testes of
      all animals included the analysis of quantitative and qualitative histologic
      parameters to assess the effect of crack-cocaine on spermatogenesis and Leydig
      cells. Apoptosis was determined by immunolabeling with caspase-3 antibodies.
      Compared to the Y(c) animals, Y(ex) animals showed a significant reduction in the
      number of stage VII tubules per testis (p = 0.02), Sertoli cells (p < 0.001) and
      elongated spermatids (p = 0.001). Comparisons between the Y(ex) and A(ex) groups
      identified a significant reduction in the number of Sertoli cells (p < 0.001) and
      round spermatids (p < 0.001) in the Y(ex) group and a significant increase in
      apoptotic Leydig cells (p = 0.04) in the A(ex) group. The experimental results
      indicate that crack-cocaine smoke inhalation induced spermatogenesis disruption
      in chronically exposed mice, particularly in pubertal mice.

PMID- 22642294
TI  - Pulmonary and cardiovascular responses of rats to inhalation of a commercial
      antimicrobial spray containing titanium dioxide nanoparticles.
AB  - Our laboratory has previously demonstrated that application of an antimicrobial
      spray product containing titanium dioxide (TiO(2)) generates an aerosol of
      titanium dioxide in the breathing zone of the applicator. The present report
      describes the design of an automated spray system and the characterization of the
      aerosol delivered to a whole body inhalation chamber. This system produced stable
      airborne levels of TiO(2) particles with a median count size diameter of 110 nm.
      Rats were exposed to 314 mg/m(3) min (low dose), 826 mg/m(3) min (medium dose),
      and 3638 mg/m(3) min (high dose) of TiO(2) under the following conditions: 2.62
      mg/m(3) for 2 h, 1.72 mg/m(3) 4 h/day for 2 days, and 3.79 mg/m(3) 4 h/day for 4
      days, respectively. Pulmonary (breathing rate, specific airway resistance,
      inflammation, and lung damage) and cardiovascular (the responsiveness of the tail
      artery to constrictor or dilatory agents) endpoints were monitored 24 h post
      exposure. No significant pulmonary or cardiovascular changes were noted at low
      and middle dose levels. However, the high dose caused significant increases in
      breathing rate, pulmonary inflammation, and lung cell injury. Results suggest
      that occasional consumer use of this antimicrobial spray product should not be a
      hazard. However, extended exposure of workers routinely applying this product to
      surfaces should be avoided. During application, care should be taken to minimize
      exposure by working under well ventilated conditions and by employing respiratory
      protection as needed. It would be prudent to avoid exposure to children or those
      with pre-existing respiratory disease.

PMID- 22642295
TI  - Initiating artificial nutrition support: a clinical judgement analysis.
AB  - BACKGROUND: Variations in the practice of artificial nutrition are partly a
      result of the judgements of clinicians. Little is known about these judgements,
      the decision processes used or the quality of the decisions that arise. The
      methodology of clinical judgement analysis describes and explains judgemental
      differences between clinicians and offers a window into why clinician choices
      sometimes fail to correspond with current best practice guidelines. METHODS: A
      clinical judgement analysis with 27 clinicians using two judgement tasks was
      carried out. Clinicians expressed their 'likelihood of feeding' and 'whether or
      not they would initiate artificial nutrition support' in response to 54 patient
      scenarios. Measures of agreement between clinicians, the degree of linear
      reasoning employed, their judgemental consistency and concordance with National
      Institute for Health and Clinical Excellence (NICE) guidelines were assessed.
      RESULTS: Clinicians' judgements varied substantially both in the amount of
      information employed and the weighting given to information. Clinicians had only
      moderate agreement with NICE recommendations and overestimated the need for
      artificial nutrition support. Suboptimal judgements were consistently applied by
      clinicians. When clinicians reasoned in more linear ways, their judgements and
      decisions improved. CONCLUSIONS: Overestimating the need for artificial
      nutritional support may inflate health service costs and increase risks for
      patients unnecessarily. A better understanding by clinicians of the information
      needed (as well as how to use it) for artificial nutrition support initiation may
      help improve clinical decision-making.

PMID- 22642297
TI  - A quantitative risk assessment for bovine spongiform encephalopathy in Japan.
AB  - A predictive case-cohort model was applied to Japanese data to analyze the
      interaction between challenge and stability factors for bovine spongiform
      encephalopathy (BSE) for the period 1985-2020. BSE risk in cattle was estimated
      as the expected number of detectable cases per year. The model was comprised of a
      stochastic spreadsheet calculation model with the following inputs: (1) the
      origin and quantity of live cattle and meat and bone meal imported into Japan,
      (2) the age distribution of native cattle, and (3) the estimated annual basic
      reproduction ratio (R(0) ) for BSE. The estimated probability of having zero
      detectable cases in Japan in 2015 was 0.90 (95% CI 0.83-0.95). The corresponding
      value for 2020 was 0.99 (95% CI 0.98-0.99). The model predicted that detectable
      cases may occur in Japan beyond 2015 because of the assumption that continued
      transmission was permitted to occur (albeit at a very low level) after the 2001
      ban on the importation and domestic use of all processed animal proteins for the
      production of animal feed and for fertilizer. These results reinforce the need
      for animal health authorities to monitor the efficacy of control measures so that
      the future course of the BSE epidemic in Japan can be predicted with greater
      certainty.

PMID- 22642296
TI  - A smallest 6 kda metalloprotease, mini-matrilysin, in living world: a
      revolutionary conserved zinc-dependent proteolytic domain- helix-loop-helix
      catalytic zinc binding domain (ZBD).
AB  - BACKGROUND: The Aim of this study is to study the minimum zinc dependent
      metalloprotease catalytic folding motif, helix B Met loop-helix C, with
      proteolytic catalytic activities in metzincin super family. The metzincin super
      family share a catalytic domain consisting of a twisted five-stranded beta sheet
      and three long alpha helices (A, B and C). The catalytic zinc is at the bottom of
      the cleft and is ligated by three His residues in the consensus sequence motif,
      HEXXHXXGXXH, which is located in helix B and part of the adjacent Met turn
      region. An interesting question is - what is the minimum portion of the enzyme
      that still possesses catalytic and inhibitor recognition?" METHODS: We have
      expressed a 60-residue truncated form of matrilysin which retains only the helix
      B-Met turn-helix C region and deletes helix A and the five-stranded beta sheet
      which form the upper portion of the active cleft. This is only 1/4 of the full
      catalytic domain. The E. coli derived 6 kDa MMP-7 ZBD fragments were purified and
      refolded. The proteolytic activities were analyzed by Mca-Pro-Leu-Gly-Leu-Dpa-Ala
      Arg-NH2 peptide assay and CM-transferrin zymography analysis. SC44463, BB94 and
      Phosphoramidon were computationally docked into the 3 day structure of the human
      MMP7 ZBD and TAD and thermolysin using the docking program GOLD. RESULTS: This
      minimal 6 kDa matrilysin has been refolded and shown to have proteolytic activity
      in the Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 peptide assay. Triton X-100 and
      heparin are important factors in the refolding environment for this mini-enzyme
      matrilysin. This minienzyme has the proteolytic activity towards peptide
      substrate, but the hexamer and octamer of the mini MMP-7 complex demonstrates the
      CM-transferrin proteolytic activities in zymographic analysis. Peptide digestion
      is inhibited by SC44463, specific MMP7 inhibitors, but not phosphorimadon.
      Interestingly, the mini MMP-7 can be processed by autolysis and producing ~ 6 ~ 7
      kDa fragments. Thus, many of the functions of the enzyme are retained indicating
      that the helix B-Met loop-helix C is the minimal functional "domain" found to
      date for the matrixin family. CONCLUSIONS: The helix B-Met loop-helix C folding
      conserved in metalloprotease metzincin super family is able to facilitate
      proteolytic catalysis for specific substrate and inhibitor recognition. The
      autolysis processing and producing 6 kDa mini MMP-7 is the smallest
      metalloprotease in living world.

PMID- 22642298
TI  - Platelet-directed gene therapy overcomes inhibitory antibodies to factor VIII.

PMID- 22642299
TI  - Impact of a weight loss program on migraine in obese adolescents.
AB  - BACKGROUND AND PURPOSE: Increased headache frequency and severity have been
      observed in obese populations, but the real impact of a weight loss treatment on
      headache has not been studied. We investigated this issue in a sample of obese
      adolescents. METHODS: In all, 135 migraineurs, aged 14-18 years, with body mass
      index (BMI) >= 97 th percentile, participating in a 12-month-long program, were
      studied before and after treatment. The program included dietary education,
      specific physical training, and behavioral treatment. RESULTS: Decreases in
      weight (P < 0.01), BMI (P < 0.01), waist circumference (P < 0.01), headache
      frequency (P < 0.01) and intensity (P < 0.01), use of acute medications (P <
      0.05), and disability (P < 0.05) were observed at the end of the first 6-month
      period and were maintained through the second 6 months. Both lower baseline BMI
      and excess change in BMI were significantly associated with better migraine
      outcomes 12 months after the intervention program. CONCLUSIONS: Significant
      improvements in both adiposity and headache data were observed in obese
      adolescents with migraine who participated in a 12-month-long interdisciplinary
      intervention program for weight loss. Initial body weight and amount of weight
      loss may be useful for clinicians to predict migraine outcomes.

PMID- 22642300
TI  - Design, synthesis, and biological activity of a novel series of human sirtuin-2
      selective inhibitors.
AB  - Selective inhibitors of human sirtuin 2 (SIRT2), a deacetylase, are candidate
      therapeutic agents for neurodegenerative diseases such as Parkinson's disease and
      Huntington's disease as well as potential tools for elucidating the biological
      functions of SIRT2. On the basis of homology models of SIRT1 and SIRT2, we
      designed and prepared a series of 2-anilinobenzamide analogues. Enzyme assays
      using recombinant SIRT1 and SIRT2 revealed that 3'-phenethyloxy-2
      anilinobenzamide analogues such as 33a and 33i are potent and selective SIRT2
      inhibitors, showing more than 3.5-fold greater SIRT2-inhibitory activity and more
      than 35-fold greater SIRT2-selectivity compared with AGK2 (3), a previously
      reported SIRT2-selective inhibitor. Compound 33a also induced a dose-dependent
      selective increase of alpha-tubulin acetylation in human colon cancer HCT116
      cells, indicating selective inhibition of SIRT2 in the cells. These 3'
      phenethyloxy-2-anilinobenzamide derivatives represent an entry into a new class
      of SIRT2-selective inhibitors.

PMID- 22642301
TI  - Structure and transport properties of a plastic crystal ion conductor:
      diethyl(methyl)(isobutyl)phosphonium hexafluorophosphate.
AB  - Understanding the ion transport behavior of organic ionic plastic crystals
      (OIPCs) is crucial for their potential application as solid electrolytes in
      various electrochemical devices such as lithium batteries. In the present work,
      the ion transport mechanism is elucidated by analyzing experimental data (single
      crystal XRD, multinuclear solid-state NMR, DSC, ionic conductivity, and SEM) as
      well as the theoretical simulations (second moment-based solid static NMR line
      width simulations) for the OIPC diethyl(methyl)(isobutyl)phosphonium
      hexafluorophosphate ([P(1,2,2,4)][PF(6)]). This material displays rich phase
      behavior and advantageous ionic conductivities, with three solid-solid phase
      transitions and a highly "plastic" and conductive final solid phase in which the
      conductivity reaches 10(-3) S cm(-1). The crystal structure shows unique channel
      like packing of the cations, which may allow the anions to diffuse more easily
      than the cations at lower temperatures. The strongly phase-dependent static NMR
      line widths of the (1)H, (19)F, and (31)P nuclei in this material have been well
      simulated by different levels of molecular motions in different phases. Thus,
      drawing together of the analytical and computational techniques has allowed the
      construction of a transport mechanism for [P(1,2,2,4)][PF(6)]. It is also
      anticipated that utilization of these techniques will allow a more detailed
      understanding of the transport mechanisms of other plastic crystal electrolyte
      materials.

PMID- 22642302
TI  - Visceral obesity is a strong predictor of perioperative outcome in patients
      undergoing laparoscopic radical nephrectomy.
AB  - Study Type--Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Obesity is a common and growing problem in
      industrialized countries, and metabolic syndrome has been the focus of much
      attention recently, particularly with respect to obesity. Obesity is thought to
      be a major factor influencing surgical complexity during abdominal surgery,
      including laparoscopic surgery. In this study, we focused on visceral obesity
      which has been recognized as the most important pathogenic factor in metabolic
      syndrome. We found that a high visceral fat area was a significant risk factor
      for a prolonged operating time. We believe that visceral obesity may greatly
      affect surgical complexity and may be a suitable index for predicting the degree
      of operating difficulty associated with laparoscopic nephrectomy. OBJECTIVE: * To
      examine the impact of visceral fat on surgical complexity in patients undergoing
      laparoscopic nephrectomy. PATIENTS AND METHODS: * We reviewed the medical records
      of 121 patients who underwent laparoscopic nephrectomy from 2006 to 2010 at our
      institution. * The total fat area, visceral fat area (VFA) and subcutaneous fat
      area were measured at the level of the umbilicus using computed tomography (CT).
      * To identify the type of obesity, we divided VFA into >= 100 cm(2) and <100
      cm(2). A VFA >= 100 cm(2) was used as the definition of visceral obesity. * We
      evaluated the impact of the VFA on technical difficulties encountered during
      laparoscopic nephrectomy by measuring operating time. RESULTS: * A significant
      correlation was observed between body mass index (BMI) and operating time (P <
      0.001, r = 0.316) in the patients undergoing laparoscopic nephrectomy. * VFA was
      also significantly correlated with operating time (P < 0.001, r = 0.348), and the
      correlation coefficient of VFA was higher than that of BMI. * Multivariate
      analysis showed that a high VFA was an independent risk factor for prolonged
      operating time (P = 0.009, odds ratio; 3.70), whereas BMI was not found to be a
      risk factor. CONCLUSIONS: * The present data indicate that measurement of VFA by
      CT is of benefit for predicting the technical difficulty associated with
      laparoscopic radical nephrectomy. * Visceral obesity, which is one factor
      involved in metabolic syndrome, has a greater impact than BMI on the complexity
      of laparoscopic radical nephrectomy.

PMID- 22642303
TI  - Iodine status in pre-school children prior to mandatory iodine fortification in
      Australia.
AB  - The iodine status of children between the ages of 5 and 15 years has been
      routinely assessed in many countries, but few studies have examined iodine status
      in pre-school children. We conducted a cross-sectional study of pre-school
      children living in Adelaide, South Australia, between 2005 and 2007. Children 1-5
      years old were identified using a unique sampling strategy to ensure that the
      study population was representative. A 3-day weighed diet record, a blood sample
      and a urine sample were obtained from each child. The median urinary iodine
      concentration (UIC) of the children (n = 279) was 129 ug L(-1), indicating iodine
      sufficiency (normal range: 100-199 ug L(-1)), but 35% of the children had a UIC <
      100 ug L(-1). The median thyroglobulin concentration of children (n = 217) was 24
      ug L(-1) and thyroglobulin concentration declined with increasing age (P =
      0.024). The mean daily iodine intake was 76 ug. The intake of iodine was lower
      than expected and highlights difficulties in accurately assessing iodine intakes.
      Further studies are needed to monitor dietary changes and iodine status in this
      age group since the implementation of mandatory fortification of bread with
      iodised salt in Australia in 2009.

PMID- 22642304
TI  - Improving solubility and pharmacokinetics of meloxicam via multiple-component
      crystal formation.
AB  - Meloxicam is a nonsteroidal anti-inflammatory drug prescribed for rheumatoid
      arthritis, osteoarthritis, postoperative pain and fever. Meloxicam exhibits low
      solubility in acidic aqueous media and a slow onset of action in biological
      subjects. An oral dosage form of meloxicam with enhanced aqueous solubility is
      desired to enable a faster onset of action and its use for mild-to-medium-level
      acute pain relief. With this in mind, we examine the solubility and
      pharmacokinetics of 12 meloxicam cocrystals with carboxylic acids. Dissolution
      studies of meloxicam and its cocrystals were performed in pH 6.5 phosphate buffer
      solutions at 37  degrees C. In addition, pharmacokinetic profiles over four hours
      were acquired after oral administration of a 10 mg/kg (meloxicam equivalent)
      solid suspension in rats. The majority of meloxicam cocrystals were found to
      achieve higher meloxicam concentrations in dissolution media and enhanced oral
      absorption compared to that of pure meloxicam. All meloxicam cocrystals were
      converted to meloxicam form I when the slurry reached equilibrium. To better
      understand how cocrystallization impacts the absorption of meloxicam after oral
      administration, correlations between the in vitro and in vivo data were explored.
      The results suggest that the meloxicam cocrystals with a faster dissolution rate
      would exhibit increased oral absorption and an earlier onset of action. 

PMID- 22642305
TI  - The natural history of motor neuron disease: assessing the impact of specialist
      care.
AB  - Many centres in the UK care for patients with motor neuron disease (MND) in a
      multidisciplinary clinic (MDC). It has been demonstrated that such care results
      in better prognosis for survival than care from a general neurology clinic (GNC).
      Whether this is due to higher use of disease-modifying interventions or an
      independent factor of attendance at a specialist clinic has not been established.
      Hence, we performed a retrospective review of hospital notes of patients with MND
      who were diagnosed and followed up in a GNC between 1998 and 2002 and in an MDC
      between 2006 and 2010. Overall, 162 patients attended a GNC, and 255 attended the
      MDC. The median survival from diagnosis was 19 months for patients who attended
      the MDC, compared to 11 months for those attending the GNC (hazard ratio 0.51,
      95% CI 0.41-0.64). The Cox hazards model identified attendance at an MDC as an
      independently positive prognostic factor (HR 1.93, 95% CI 1.37-2.72, p < 0.001).
      We concluded that care at an MDC improves survival. While this effect is
      augmented by the increased use of riluzole, NIV and PEG, the data suggest that
      coordinated care independently improves the prognosis of MND patients.

PMID- 22642306
TI  - The purview of nitric oxide nanoparticle therapy in infection and wound healing.

PMID- 22642307
TI  - Endosperm: food for humankind and fodder for scientific discoveries.
AB  - The endosperm is an essential constituent of seeds in flowering plants. It
      originates from a fertilization event parallel to the fertilization that gives
      rise to the embryo. The endosperm nurtures embryo development and, in some
      species including cereals, stores the seed reserves and represents a major source
      of food for humankind. Endosperm biology is characterized by specific features,
      including idiosyncratic cellular controls of cell division and epigenetic
      controls associated with parental genomic imprinting. This review attempts a
      comprehensive summary of our current knowledge of endosperm development and
      highlights recent advances in this field.

PMID- 22642309
TI  - Survey on the phase transitions and their effect on the ion-exchange and on the
      proton-conduction properties of a flexible and robust Zr phosphonate coordination
      polymer.
AB  - The flexible zirconium tetraphosphonate coordination polymer with formula
      Zr(O(3)PCH(2))(2)N-C(6)H(10)-N(O(3)CH(2)P)(2)X(2-x)H(2+x).nH(2)O (X = H, Li, Na,
      K, 0 < x < 1, 4 < n < 7.5) (1) possesses an open framework structure with 1D
      cavities decorated with polar and acids P?O and P-OH groups. 1 has been fully
      protonated by adding HCl and then subjected to several acid-base ion-exchange
      reactions with alkaline metals hydroxides. 1 is a very robust coordination
      polymer because it can be regenerated in H- form using strong acid solutions and
      ri-exchanged several times without hydrolysis and loss of crystallinity. The
      flexibility of 1 has been also studied by means of TDXD (temperature dependent X
      ray diffraction) evidencing remarkable phase transformations that lead to a
      different disposition of the water molecules. These transformations also
      influence the accessibility of the cations on the P-OH groups placed inside the
      channels and thus the ion-exchange properties. The dependence of the proton
      conductivity properties on these phase transitions has been also investigated and
      discussed.

PMID- 22642310
TI  - Association between serum retinol-binding protein 4 concentrations and clinical
      indices in subjects with type 2 diabetes: a meta-analysis.
AB  - BACKGROUND: Retinol-binding protein (RBP4) is an adipokine that may be important
      in type 2 diabetes. Previous studies have examined the association between serum
      RBP4 concentrations and clinical indices in patients with type 2 diabetes,
      although the results obtained have been inconsistent. We conducted a meta
      analysis aiming to investigate the association between serum RBP4 concentrations
      and clinical indicators of diabetes, renal function, metabolic syndrome and
      obesity in subjects with type 2 diabetes. METHODS: MEDLINE, EMBASE and CINAHL
      databases were searched from 2005 through November 2011, and the search
      identified 21 clinical variables from seven studies (total n = 1406). For each
      variable, summary correlation coefficients (r(s) ) were estimated using a random
      effects meta-analysis. RESULTS: None of the diabetes markers were correlated with
      serum RBP4 concentrations in subjects with type 2 diabetes, whereas all of the
      renal function markers and many metabolic syndrome markers were significantly
      correlated. Summary correlation coefficients and 95% confidence intervals (CIs)
      were -0.36 (95% CI = -0.51 to -0.18) for creatinine clearance, -0.39 (95% CI = 
      0.44 to -0.33) for estimated glomerular filtration rate and 0.53 (95% CI = 0.30
      0.71) for creatinine concentration. In addition, plasma triglyceride
      concentrations (r(s) = 0.22; 95% CI = 0.11-0.32), plasma total cholesterol
      concentrations [r(s) = 0.14 (95% CI = 0.05-0.23)] and low-density lipoprotein
      cholesterol level (r(s) = 0.14; 95% CI = 0.02-0.25) were positively correlated
      with serum RBP4 concentrations. CONCLUSIONS: The results obtained in the present
      study suggest that serum RBP4 concentrations in patients with type 2 diabetes may
      be associated with diabetes-related renal dysfunction and imbalances in lipid
      metabolism.

PMID- 22642311
TI  - Evaluation of model-based versus non-parametric monaural noise-reduction
      approaches for hearing aids.
AB  - OBJECTIVE: Single channel noise reduction has been well investigated and seems to
      have reached its limits in terms of speech intelligibility improvement, however,
      the quality of such schemes can still be advanced. This study tests to what
      extent novel model-based processing schemes might improve performance in
      particular for non-stationary noise conditions. DESIGN: Two prototype model-based
      algorithms, a speech-model-based, and a auditory-model-based algorithm were
      compared to a state-of-the-art non-parametric minimum statistics algorithm. A
      speech intelligibility test, preference rating, and listening effort scaling were
      performed. Additionally, three objective quality measures for the signal,
      background, and overall distortions were applied. For a better comparison of all
      algorithms, particular attention was given to the usage of the similar Wiener
      based gain rule. STUDY SAMPLE: The perceptual investigation was performed with
      fourteen hearing-impaired subjects. RESULTS: The results revealed that the non
      parametric algorithm and the auditory model-based algorithm did not affect speech
      intelligibility, whereas the speech-model-based algorithm slightly decreased
      intelligibility. In terms of subjective quality, both model-based algorithms
      perform better than the unprocessed condition and the reference in particular for
      highly non-stationary noise environments. CONCLUSION: Data support the hypothesis
      that model-based algorithms are promising for improving performance in non
      stationary noise conditions.

PMID- 22642312
TI  - Retrocochlear hearing loss in infants: a case study of juvenile pilocytic
      astrocytoma.
AB  - OBJECTIVE: The purpose of this paper was to describe a child with brainstem
      juvenile pilocytic astrocytoma (JPA) and associated auditory symptoms. DESIGN:
      Case study of a 5-year-old female who presented with a complaint of headaches,
      accompanied with a history of symptoms that could be associated with a left
      unilateral congenital auditory neuropathy. She was later diagnosed with a large,
      left-sided posterior fossa mass determined to be a JPA. STUDY SAMPLE: Case study
      of a child identified at birth with a constellation of symptoms consistent with
      unilateral auditory neuropathy spectrum disorder (ANSD). RESULTS: The early onset
      symptoms, that can be the same for ANSD or for a brainstem tumor that involves
      the auditory nerve, suggests that the JPA was congenital. This child, if
      initially followed by neurology may not have been identified earlier with this
      tumor, however a baseline MRI or monitoring neuroimaging may have been available
      for reference or led to earlier detection of the lesion. It may not have changed
      her management, however, this case stresses the importance of the recommendations
      in the 'Guidelines for Identification and Management of Infants and Young
      Children with Auditory Neuropathy Spectrum Disorder' that include a referral to a
      neurologist for a baseline assessment and neuroimaging. CONCLUSION: An undetected
      JPA can have the same audiological clinical presentation as a unilateral ANSD.
      This case description highlights the need to heighten awareness for neurological
      and radiological monitoring in cases of ANSD, especially when the presentation is
      unilateral.

PMID- 22642313
TI  - Affective development in advanced old age: analyses of terminal change in
      positive and negative affect.
AB  - Late-life development of affect may unfold terminal changes that are driven more
      by end-of-life processes and not so much by time since birth. This study aimed to
      explore time-to-death-related effects in measures of affect in a sample of the
      very old. We used longitudinal data (2 measurement occasions: 2002 and 2003) from
      140 deceased participants, covering a period of up to 9 years to death, from a
      German oldest-old sample between 80 and 90 years old at baseline measurement
      (Projects ENABLE-AGE and LateLine). Nonlinear time-to-death and age effects on
      baseline level and intraindividual 1-year changes in positive affect (PA) and
      negative affect (NA) were analyzed with latent change score models. With respect
      to PA, no time-to-death-related effects were discovered, but linear age-related
      decline was found. For NA, time-to-death effects were found for both baseline
      level and 1-year change, indicating an increase of NA closer to death, which
      turns around to a rapid reduction of NA in the approach of the end of life. These
      effects suggest a twofold dynamic of terminal changes in NA. First, a general
      increase of NA across a larger period preceding death potentially mirrors basic
      processes of degradation of the human system. Second, approaching the end, these
      processes may exhaust negative activation, prompting a terminal drop of NA close
      to death.

PMID- 22642314
TI  - Using generalized additive modeling to empirically identify thresholds within the
      ITERS in relation to toddlers' cognitive development.
AB  - Research linking high-quality child care programs and children's cognitive
      development has contributed to the growing popularity of child care quality
      benchmarking efforts such as quality rating and improvement systems (QRIS).
      Consequently, there has been an increased interest in and a need for approaches
      to identifying thresholds, or cutpoints, in the child care quality measures used
      in these benchmarking efforts that differentiate between different levels of
      children's cognitive functioning. To date, research has provided little guidance
      to policymakers as to where these thresholds should be set. Using the Early
      Childhood Longitudinal Study, Birth Cohort (ECLS-B) data set, this study explores
      the use of generalized additive modeling (GAM) as a method of identifying
      thresholds on the Infant/Toddler Environment Rating Scale (ITERS) in relation to
      toddlers' performance on the Mental Development subscale of the Bayley Scales of
      Infant Development (the Bayley Mental Development Scale Short Form-Research
      Edition, or BMDSF-R). The present findings suggest that simple linear models do
      not always correctly depict the relationships between ITERS scores and BMDSF-R
      scores and that GAM-derived thresholds were more effective at differentiating
      among children's performance levels on the BMDSF-R. Additionally, the present
      findings suggest that there is a minimum threshold on the ITERS that must be
      exceeded before significant improvements in children's cognitive development can
      be expected. There may also be a ceiling threshold on the ITERS, such that beyond
      a certain level, only marginal increases in children's BMDSF-R scores are
      observed.

PMID- 22642315
TI  - Artificially depleted plasmas are not necessarily commutable with native patient
      plasmas for International Sensitivity Index calibration and International
      Normalized Ratio derivation: a rebuttal.

PMID- 22642316
TI  - Exposures from chrysotile-containing joint compound: evaluation of new model
      relating respirable dust to fiber concentrations.
AB  - The potential for fiber exposure during historical use of chrysotile-containing
      joint compounds (JCC) has been documented, but the published data are of limited
      use for reconstructing exposures and assessing worker risk. Consequently, fiber
      concentration distributions for workers sanding JCC were independently derived by
      applying a recently developed model based on published dust measurements from
      sanding modern-day (asbestos-free) joint compound and compared to fiber
      concentration distributions based on limited historical measurements. This new
      procedure relies on factors that account for (i) differences in emission rates
      between modern-day and JCC and (ii) the number of fibers (quantified by phase
      contrast microscopy [PCM]) per mass of dust generated by sanding JCC, as
      determined in a bench-scale chamber study using a recreated JCC, that convert
      respirable dust concentrations to fiber concentrations. Airborne respirable PCM
      fiber concentration medians (and 95% confidence intervals) derived for output
      variables using the new procedure were 0.26 (0.039, 1.7) f/cm(3)  and 0.078
      (0.013, 0.47) f/cm(3) , and corresponding total fiber concentrations were 1.2
      (0.17, 9.2) f/cm(3)  and 0.37 (0.056, 2.5) f/cm(3) , in enclosed and nonenclosed
      environments, respectively. Corresponding estimates of respirable and total PCM
      fiber concentrations measured historically during sanding of asbestos-containing
      joint compound-adjusted for differences between peak and time-weighted average
      (TWA) concentrations and documented analytical preparation and sampling artifacts
      were 0.15 (0.019, 0.95) f/cm(3)  and 0.86 (0.11, 5.4) f/cm(3) , respectively. The
      PCM-fiber concentration distributions estimated using the new procedure bound the
      distribution estimated from adjusted TWA historical fiber measurements,
      suggesting reasonable consistency of these estimates taking into account
      uncertainties addressed in this study.

PMID- 22642317
TI  - Raman and infrared spectroscopy of alpha and beta phases of thin nickel hydroxide
      films electrochemically formed on nickel.
AB  - The present work utilizes Raman and infrared (IR) spectroscopy, supported by X
      ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) to re-examine
      the fine structural details of Ni(OH)(2), which is a key material in many energy
      related applications. This work also unifies the large body of literature on the
      topic. Samples were prepared by the galvanostatic basification of nickel salts
      and by aging the deposits in hot KOH solutions. A simplified model is presented
      consisting of two fundamental phases (alpha and beta) of Ni(OH)(2) and a range of
      possible structural disorder arising from factors such as impurities, hydration,
      and crystal defects. For the first time, all of the lattice modes of beta
      Ni(OH)(2) have been identified and assigned using factor group analysis.
      Ni(OH)(2) films can be rapidly identified in pure and mixed samples using Raman
      or IR spectroscopy by measuring their strong O-H stretching modes, which act as
      fingerprints. Thus, this work establishes methods to measure the phase, or
      phases, and disorder at a Ni(OH)(2) sample surface and to correlate desired
      chemical properties to their structural origins.

PMID- 22642318
TI  - Smoking and caesarean deliveries: major negative predictors for breastfeeding in
      the mother-child cohort in Crete, Greece (Rhea study).
AB  - Although benefits of breastfeeding have been widely promoted and accepted,
      exclusive breastfeeding for the first 6 months of life is far from the norm in
      many countries. In a prospective mother-child cohort study in Crete, Greece
      ('Rhea' study), we assessed the frequency of breastfeeding and its socio
      demographic predictors. Information on breastfeeding was available for a period
      of 18 months post-partum for a cohort of 1181 mothers and their 1208 infants. The
      frequency of exclusive and predominant breastfeeding in the first month post
      partum was 17.8% and 3.4%, respectively, with almost three-quarters of women
      (73.6%) ceasing any breastfeeding after 4 months post-partum. Women were less
      likely to initiate breastfeeding if they had a caesarean delivery (CD), whereas
      they were more likely to initiate breastfeeding if they had a higher education or
      gave birth to a private clinic. Among women breastfeeding, those who had a CD,
      were ex-smokers or smokers during pregnancy had a statistically significant
      shorter duration of breastfeeding, whereas higher education and being on leave
      from work were associated with a longer duration of breastfeeding. Study findings
      suggest suboptimal levels of exclusive and any breastfeeding and difficulty
      maintaining longer breastfeeding duration. CD and smoking are common in Greece
      and are strong negative predictors for breastfeeding initiation and/or duration,
      necessitating targeting women at risk early in the prenatal period so as to have
      a meaningful increase of breastfeeding practices in future cohorts of mothers. 

PMID- 22642319
TI  - Structural and enzymatic analyses reveal the binding mode of a novel series of
      Francisella tularensis enoyl reductase (FabI) inhibitors.
AB  - Because of structural and mechanistic differences between eukaryotic and
      prokaryotic fatty acid synthesis enzymes, the bacterial pathway, FAS-II, is an
      attractive target for the design of antimicrobial agents. We have previously
      reported the identification of a novel series of benzimidazole compounds with
      particularly good antibacterial effect against Francisella tularensis, a Category
      A biowarfare pathogen. Herein we report the crystal structure of the F.
      tularensis FabI enzyme in complex with our most active benzimidazole compound
      bound with NADH. The structure reveals that the benzimidazole compounds bind to
      the substrate site in a unique conformation that is distinct from the binding
      motif of other known FabI inhibitors. Detailed inhibition kinetics have confirmed
      that the compounds possess a novel inhibitory mechanism that is unique among
      known FabI inhibitors. These studies could have a strong impact on future
      antimicrobial design efforts and may reveal new avenues for the design of FAS-II
      active antibacterial compounds.

PMID- 22642320
TI  - Diabetes mellitus affects the duration of action of vecuronium in dogs.
AB  - OBJECTIVE: To compare the duration of action of vecuronium in diabetic dogs with
      a control group. STUDY DESIGN: Prospective clinical study. ANIMALS: Forty client
      owned diabetic (n = 20) and non-diabetic dogs. METHODS: Dogs were considered free
      from other concurrent disease based on clinical examination and laboratory data.
      After pre-anaesthetic medication with acepromazine and methadone, anaesthesia was
      induced with intravenous (IV) propofol and maintained with isoflurane-nitrous
      oxide in oxygen. Neuromuscular blockade (NMB) was achieved with vecuronium, 0.1
      mg kg(-1) IV and its effects recorded by palpation (pelvic limb digital
      extension) and electromyography (m. tibialis cranialis) of responses (twitches;
      T) to repeated train-of-four (TOF) nerve stimulation. Time to onset of NMB was
      the period between vecuronium injection and loss of fourth twitch (T4) in the TOF
      pattern recorded by EMG and palpation. Duration of NMB was defined as the time
      from drug administration to return of T1 by palpation (T1(tactile) ) and EMG
      (T1(EMG) ). Times to return of T2-4 were also recorded. Time from induction of
      anaesthesia to vecuronium injection was recorded. Heart rate, non-invasive mean
      arterial pressure, body temperature, end-tidal isoflurane and end-tidal CO(2)
      concentrations were recorded at onset of NMB and when T1(EMG) returned. Loss and
      return of palpable and EMG responses for diabetic and non-diabetic dogs were
      compared using t-tests and Mann Whitney U-tests. RESULTS: There were significant
      (p < 0.05) differences between diabetic and non-diabetic dogs for the return of
      all four palpable and EMG responses. Times (mean +/- SD) for return of
      T1(tactile) were 13.2 +/- 3.5 and 16.9 +/- 4.2 minutes in diabetic and non
      diabetic dogs respectively. There were no differences between diabetic and non
      diabetic dogs in the time to onset of vecuronium with EMG or tactile monitoring.
      CONCLUSIONS AND CLINICAL RELEVANCE: The duration of action of vecuronium was
      shorter in diabetic dogs as indicated by both tactile and EMG monitoring.

PMID- 22642322
TI  - Synthesis of YBa2Cu3O(7-delta) and Y2BaCuO5 nanocrystalline powders for YBCO
      superconductors using carbon nanotube templates.
AB  - We fabricate nanosized superconducting YBa(2)Cu(3)O(7-delta) (Y-123) and
      nonsuperconducting Y(2)BaCuO(5) (Y-211) powders using carbon nanotubes as
      template. The mean particle size of Y-123 and Y-211 is 12 and 30 nm,
      respectively. The superconducting transition temperature of the Y-123 nanopowder
      is 90.9 K, similar to that of commercial, micrometer-scale powders fabricated by
      conventional processing. The elimination of carbon and the formation of a high
      purity superconducting phase both on the micro- and macroscale is confirmed by
      Raman spectroscopy and X-ray diffraction. We also demonstrate improvement in the
      superconducting properties of YBCO single grain bulk samples fabricated using the
      nanosize Y-211 powder, both in terms of trapped field and critical current
      density. The former reaches 553 mT at 77 K, with a ~20% improvement compared to
      samples fabricated from commercial powders. Thus, our processing method is an
      effective source of pinning centers in single grain superconductors.

PMID- 22642323
TI  - Motor endplate disease affects neuromuscular junction maturation.
AB  - Postnatal formation of the neuromuscular synapse requires complex interactions
      among nerve terminal, muscle fibres and terminal Schwann cells. In motor endplate
      disease (med) mice, neuromuscular transmission is severely impaired without
      alteration of axonal conduction and a lethal paralytic phenotype occurs during
      the postnatal period. The med phenotype appears at a crucial stage of the
      neuromuscular junction development, corresponding to the increase in terminal
      Schwann cell number, the elimination of the multiple innervations and the pre-
      and postsynaptic maturation. Here we investigated the early cellular and
      molecular consequences of the med mutation on neuromuscular junction development.
      We observed that cellular defects preceded overt clinical phenotype. The first
      detectable cellular effect of the mutation at the onset of the clinical phenotype
      was a drastic reduction in the number of terminal Schwann cells, in part due to
      an increase in glial apoptosis, and a delayed maturation of motor endplates. We
      also showed that, in terminally ill animals, mono-innervation was not achieved,
      synaptic vesicles had accumulated in the presynaptic compartment and, finally,
      the size of motor endplates was reduced. All together, our findings suggested
      that the clinical weakness in these mutant mice was likely to be related to
      postnatal structural abnormalities of the neuromuscular junction maturation.

PMID- 22642324
TI  - B-cell-directed therapy: which B cells should be targeted and how?

PMID- 22642325
TI  - Bispecific antibodies and diabodies for cancer immunotherapy.

PMID- 22642326
TI  - How necessary is it to revaccinate hemopoietic transplant recipients?

PMID- 22642327
TI  - News & views in ... Immunotherapy.

PMID- 22642328
TI  - Research highlights: highlights from the latest articles in optimizing vaccine
      development.

PMID- 22642329
TI  - Research highlights: highlights from the latest articles in cancer immunotherapy.

PMID- 22642330
TI  - Absence of CD4 T-cell help provides a robust CD8 T-cell response while inducing
      effective memory in a preclinical model of melanoma.
AB  - Immunotherapy strategies for cancer are focused on inducing effective and
      specific cytotoxic responses mediated by CD8 T cells. On the other hand,
      immunosuppressive mechanisms induced by the tumor, such as the generation of
      tumor-specific CD4(+)CD25(+)FoxP3(+) Tregs, conspire against the efficacy of
      immunotherapies. It has been considered that, similar to what has been observed
      in the context of immunological responses towards microbes, CD4 help is
      indispensable for the development of a successful and long-lasting (memory) CD8
      immune response. In the recent article, Cote et al. reported that, in a mouse
      model of melanoma, total ablation of CD4 help does not hamper the development of
      a specific antitumor memory CD8 response. In addition, ablation of CD4 was more
      successful than strategies to deplete CD25 Tregs in generating memory CD8 T
      cells. These data opens the door for therapies destined to induce effective
      antitumor immune responses by ablation of whole CD4 T-cell populations.

PMID- 22642331
TI  - Depletion of Tregs for adoptive T-cell therapy using CD44 and CD137 as selection
      markers.
AB  - Several types of cancer have been shown to be susceptible to cellular immune
      responses, leading to investigations using various forms of T cell-based, tumor
      directed immunotherapy. One potential obstacle for the successful application of
      these therapies is the suppressive function of Tregs. Goldstein and colleagues
      evaluate a strategy to identify and remove Tregs from an adoptive T-cell therapy
      product generated by in vivo vaccination. They demonstrate that the depletion of
      Tregs characterized by CD44 and CD137 expression enhances antitumor immunity in
      their mouse model.

PMID- 22642332
TI  - Beneficial effects of immunotherapy with extracts derived from Actinomycetales on
      rats with spontaneous obesity and diabetes.
AB  - AIMS: To determine whether immunotherapy with heat-killed, selected
      Actinomycetales species could influence the progression of spontaneous Type 2
      diabetes mellitus and obesity in a rat model. MATERIALS & METHODS: Preparations
      of either Gordonia bronchialis, Tsukamurella inchonensis or a saline placebo were
      given by three subcutaneous injections, 30 days apart, starting when rats were
      aged 120 days, just before development of Type 2 diabetes mellitus, and at day
      440, when the disease was well established. Bodyweight, blood sugar, cholesterol,
      triglycerides and insulin levels were measured to determine the effects and at
      the end of the experiments, animals were subjected to necropsy. RESULTS: The
      development of Type 2 diabetes mellitus was prevented by both reagents, most
      effectively by T. inchonensis. In the treatment experiment, the effects of the
      disease were reduced by both treatments, markedly so by T. inchonensis. In both
      experiments obesity was reduced in treated animals. The possible mechanisms of
      action are discussed. CONCLUSION: Our findings suggest that Type 2 diabetes
      mellitus in the studied rats is associated with obesity, and that both diabetes
      and obesity can be prevented or improved by treatment with Actinomycetales immune
      modulators.

PMID- 22642333
TI  - Immunotherapy in nonmelanoma skin cancer.
AB  - Nonmelanoma skin cancer is the most common type of cancer in humans. The role of
      the immune system in the prevention and regression of cancer is significant. UV
      radiation, being the most important risk factor in the development of skin
      cancer, has a suppressive effect on local and systemic immune effectors.
      Different immunotherapeutic approaches have been used for the treatment of
      nonmelanoma skin cancer including adoptive T-cell therapies, vaccine-based
      strategies, cytokines and monoclonal antibodies. The most important advancement
      with promising effects in the field of nonmelanoma skin cancer immunotherapy is
      the topical immune response modifier imiquimod. In addition, immunoprevention has
      been successfully applied for autosomal dominant basal cell nevus syndrome.
      Immunotherapeutic approaches provide a new modality for the treatment of
      recurrent or multiple nonmelanoma skin tumors.

PMID- 22642336
TI  - Orthotopic administration of (213)Bi-bevacizumab inhibits progression of PC3
      xenografts in the prostate.
AB  - AIM: To investigate orthotopic targeted alpha-radioimmunotherapy for the control
      of early-stage PC3 prostate cancer nude mouse xenografts using the radiolabeled
      bevacizumab (BZ) immunoconjugate ((213)Bi-BZ), which emits short-range alpha
      radiation. MATERIALS & METHODS: 10(6) PC3 human prostate cancer cells were
      injected into the lower capsule of the mouse prostate gland 1 week prior to alpha
      radioimmunotherapy. Mice were euthanized and assessed for tumour growth at 2 (two
      mice), 4 (two mice) and 6 weeks (three mice) post-therapy. The no-therapy control
      mice received a saline injection in equal volume to each BZ administration.
      RESULTS: (213)Bi-BZ is significantly more efficacious in inhibiting xenograft
      progression in the prostate gland compared with BZ alone (p = 0.009) and when
      compared with the 'no therapy' protocol (p < 0.0001). CONCLUSION: Orthotopic
      administration of (213)Bi-BZ greatly improves the early control of organ-confined
      prostate cancer compared with BZ alone (p < 0.01).

PMID- 22642338
TI  - Cardiac vagal tone predicts inhibited attention to fearful faces.
AB  - The neurovisceral integration model (Thayer, J. F., & Lane, R. D., 2000, A model
      of neurovisceral integration in emotion regulation and dysregulation. Journal of
      Affective Disorders, 61, 201-216. doi:10.1016/S0165-0327(00)00338-4) proposes
      that individual differences in heart rate variability (HRV)-an index of cardiac
      vagal tone-are associated with attentional and emotional self-regulation. In this
      article, we demonstrate that individual differences in resting HRV predict the
      functioning of the inhibition of return (IOR), an inhibitory attentional
      mechanism highly adaptive to novelty search, in response to affectively
      significant face cues. As predicted, participants with lower HRV exhibited a
      smaller IOR effect to fearful versus neutral face cues than participants with
      higher HRV, which shows a failure to inhibit attention from affectively
      significant cues and instigate novelty search. In contrast, participants with
      higher HRV exhibited similar IOR effects to fearful and neutral face cues, which
      shows an ability to inhibit attention from cues and instigate novelty search.
      Their ability to inhibit attention was most pronounced to high spatial frequency
      fearful face cues, suggesting that this effect may be mediated by cortical
      mechanisms. The current research demonstrates that individual differences in HRV
      predict attentional inhibition and suggests that successful inhibition and
      novelty search may be mediated by cortical inhibitory mechanisms among people
      with high cardiac vagal tone.

PMID- 22642334
TI  - Combination strategies to enhance antitumor ADCC.
AB  - The clinical efficacy of monoclonal antibodies as cancer therapeutics is largely
      dependent upon their ability to target the tumor and induce a functional
      antitumor immune response. This two-step process of ADCC utilizes the response of
      innate immune cells to provide antitumor cytotoxicity triggered by the
      interaction of the Fc portion of the antibody with the Fc receptor on the immune
      cell. Immunotherapeutics that target NK cells, gammadelta T cells, macrophages
      and dendritic cells can, by augmenting the function of the immune response,
      enhance the antitumor activity of the antibodies. Advantages of such combination
      strategies include: the application to multiple existing antibodies (even across
      multiple diseases), the feasibility (from a regulatory perspective) of combining
      with previously approved agents and the assurance (to physicians and trial
      participants) that one of the ingredients - the antitumor antibody - has proven
      efficacy on its own. Here we discuss current strategies, including biologic
      rationale and clinical results, which enhance ADCC in the following ways:
      strategies that increase total target-monoclonal antibody-effector binding,
      strategies that trigger effector cell 'activating' signals and strategies that
      block effector cell 'inhibitory' signals.

PMID- 22642339
TI  - Promoting intergroup contact by changing beliefs: group malleability, intergroup
      anxiety, and contact motivation.
AB  - Intergroup contact plays a crucial role in moderating long-term conflicts.
      Unfortunately, the motivation to make contact with outgroup members is usually
      very low in such conflicts. We hypothesized that one limiting factor is the
      belief that groups cannot change, which leads to increased intergroup anxiety and
      decreased contact motivation. To test this hypothesis, we experimentally
      manipulated beliefs about group malleability in the context of the conflict
      between Greek and Turkish Cypriots and then assessed intergroup anxiety and
      motivation to engage in intergroup contact. Turkish Cypriots who were led to
      believe that groups can change (with no mention of the specific groups involved)
      reported lower levels of intergroup anxiety and higher motivation to interact and
      communicate with Greek Cypriots in the future, compared with those who were led
      to believe that groups cannot change. This effect of group malleability
      manipulation on contact motivation was mediated by intergroup anxiety.

PMID- 22642335
TI  - The potential of mesenchymal stromal cells as a novel cellular therapy for
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the CNS
      for which only partially effective therapies exist. Intense research defining the
      underlying immune pathophysiology is advancing both the understanding of MS as
      well as revealing potential targets for disease intervention. Mesenchymal stromal
      cell (MSC) therapy has the potential to modulate aberrant immune responses
      causing demyelination and axonal injury associated with MS, as well as to repair
      and restore damaged CNS tissue and cells. This article reviews the
      pathophysiology underlying MS, as well as providing a cutting-edge perspective
      into the field of MSC therapy based upon the experience of authors intrinsically
      involved in MS and MSC basic and translational science research.

PMID- 22642340
TI  - Working memory load reduces facilitated processing of threatening faces: an ERP
      study.
AB  - The present study tested the hypothesis that facilitated processing of
      threatening faces depends on working memory load. Participants judged the gender
      of angry versus happy faces while event-related brain potentials were recorded.
      Working memory load was manipulated within subjects by the mental rehearsal of
      one- versus eight-digit numbers. Behavioral results showed that the relative slow
      down to angry compared to happy faces in the gender-naming task (i.e., the
      negativity bias) was eliminated under high working memory load. Under low (but
      not high) load, N2 amplitudes were smaller to angry compared to happy faces.
      Moreover, high load reduced LPP amplitude and eliminated the enhanced LPP to
      angry compared to happy faces that were present under low load. These results
      suggest that working memory load improves attentional control, and reduces
      sustained attention for distracting negative expressions. Taken together, these
      findings demonstrate that facilitated processing of threatening cues may be
      contingent on cognitive resources.

PMID- 22642341
TI  - If it makes you happy: engaging in kind acts increases positive affect in
      socially anxious individuals.
AB  - Social anxiety is associated with low positive affect (PA), a factor that can
      significantly affect psychological well-being and adaptive functioning. Despite
      suggestions that individuals with high levels of social anxiety would benefit
      from PA enhancement, the feasibility of doing so remains an unanswered question.
      Accordingly, in the current study, individuals with high levels of social anxiety
      (N = 142) were randomly assigned to conditions designed to enhance PA (Kind
      Acts), reduce negative affect (NA; Behavioral Experiments), or a neutral control
      (Activity Monitoring). All participants engaged in the required activities for 4
      weeks and completed prepost questionnaires measuring mood and social goals, as
      well as weekly email ratings of mood, anxiety, and social activities. Both the
      prepost and weekly mood ratings revealed that participants who engaged in kind
      acts displayed significant increases in PA that were sustained over the 4 weeks
      of the study. No significant changes in PA were observed in the other conditions.
      The increase in hedonic functioning was not due to differential compliance,
      frequency of social activities, or an indirect effect of NA reduction. In
      addition, participants who engaged in kind acts displayed an increase in
      relationship satisfaction and a decrease in social avoidance goals, whereas no
      significant changes in these variables were observed in the other conditions.
      This study is the first to demonstrate that positive affect can be increased in
      individuals with high levels of social anxiety and that PA enhancement strategies
      may result in wider social benefits. The role of PA in producing those benefits
      requires further study.

PMID- 22642342
TI  - Emotion regulation in Asperger's syndrome and high-functioning autism.
AB  - It is generally thought that individuals with Asperger's syndrome and high
      functioning autism (AS/HFA) have deficits in theory of mind. These deficits have
      been previously linked to problems with social cognition. However, we reasoned
      that AS/HFA individuals' Theory of Mind deficits also might lead to problems with
      emotion regulation. To assess emotional functioning in AS/HFA, 27 AS/HFA adults
      (16 women) and 27 age-, gender-, and education-matched typically developing (TD)
      participants completed a battery of measures of emotion experience, labeling, and
      regulation. With respect to emotion experience, individuals with AS/HFA reported
      higher levels of negative emotions, but similar levels of positive emotions,
      compared with TD individuals. With respect to emotion labeling, individuals with
      AS/HFA had greater difficulties identifying and describing their emotions, with
      approximately two-thirds exceeding the cutoff for alexithymia. With respect to
      emotion regulation, individuals with AS/HFA used reappraisal less frequently than
      TD individuals and reported lower levels of reappraisal self-efficacy. Although
      AS/HFA individuals used suppression more frequently than TD individuals, no
      difference in suppression self-efficacy was found. It is important to note that
      these differences in emotion regulation were evident even when controlling for
      emotion experience and labeling. Implications of these deficits are discussed,
      and future research directions are proposed.

PMID- 22642343
TI  - Conscientiousness predicts greater recovery from negative emotion.
AB  - Greater levels of conscientiousness have been associated with lower levels of
      negative affect. We focus on one mechanism through which conscientiousness may
      decrease negative affect: effective emotion regulation, as reflected by greater
      recovery from negative stimuli. In 273 adults who were 35-85 years old, we
      collected self-report measures of personality including conscientiousness and its
      self-control facet, followed on average 2 years later by psychophysiological
      measures of emotional reactivity and recovery. Among middle-aged adults (35-65
      years old), the measures of conscientiousness and self-control predicted greater
      recovery from, but not reactivity to, negative emotional stimuli. The effect of
      conscientiousness and self-control on recovery was not driven by other
      personality variables or by greater task adherence on the part of high
      conscientiousness individuals. In addition, the effect was specific to negative
      emotional stimuli and did not hold for neutral or positive emotional stimuli.

PMID- 22642344
TI  - The relationship between self-distancing and the duration of negative and
      positive emotional experiences in daily life.
AB  - Extant research suggests that self-distancing facilitates adaptive self
      reflection of negative emotional experiences. However, this work operationalizes
      adaptive self-reflection in terms of a reduction in the intensity of negative
      emotion, ignoring other important aspects of emotional experience such as emotion
      duration. Moreover, prior research has predominantly focused on how self
      distancing influences emotional reactivity in response to reflecting on negative
      experiences, leaving open questions concerning how this process operates in the
      context of positive experiences. We addressed these issues by examining the
      relationship between self-distancing and the duration of daily negative and
      positive emotions using a daily diary methodology. Discrete-time survival
      analyses revealed that reflecting on both daily negative (Studies 1 and 2) and
      positive events (Study 2) from a self-distanced perspective was associated with
      shorter emotions compared with reflecting on such events from a self-immersed
      perspective. The basic science and clinical implications of these findings are
      discussed.

PMID- 22642345
TI  - Pursuing happiness in everyday life: the characteristics and behaviors of online
      happiness seekers.
AB  - Although the last decade has witnessed mounting research on the development and
      evaluation of positive interventions, investigators still know little about the
      target population of such interventions: happiness seekers. The present research
      asked three questions about happiness seekers: (1) What are their general
      characteristics?, (2) What do they purposefully do to become happier?, and (3)
      How do they make use of self-help resources? In Study 1, we identified two
      distinct clusters of online happiness seekers. In Study 2, we asked happiness
      seekers to report on their use of 14 types of happiness-seeking behaviors. In
      Study 3, we tracked happiness seekers' usage of an iPhone application that
      offered access to eight different happiness-increasing activities, and assessed
      their resulting happiness and mood improvements. Together, these studies provide
      a preliminary portrait of happiness seekers' characteristics and naturalistic
      behaviors.

PMID- 22642346
TI  - Beyond attentional bias: a perceptual bias in a dot-probe task.
AB  - Previous dot-probe studies indicate that threat-related face cues induce a bias
      in spatial attention. Independently of spatial attention, a recent psychophysical
      study suggests that a bilateral fearful face cue improves low spatial-frequency
      perception (LSF) and impairs high spatial-frequency perception (HSF). Here, we
      combine these separate lines of research within a single dot-probe paradigm. We
      found that a bilateral fearful face cue, compared with a bilateral neutral face
      cue, speeded up responses to LSF targets and slowed down responses to HSF
      targets. This finding is important, as it shows that emotional cues in dot-probe
      tasks not only bias where information is preferentially processed (i.e., an
      attentional bias in spatial location), but also bias what type of information is
      preferentially processed (i.e., a perceptual bias in spatial frequency).

PMID- 22642347
TI  - The effect of poser race on the happy categorization advantage depends on
      stimulus type, set size, and presentation duration.
AB  - The question as to whether poser race affects the happy categorization advantage,
      the faster categorization of happy than of negative emotional expressions, has
      been answered inconsistently. Hugenberg (2005) found the happy categorization
      advantage only for own race faces whereas faster categorization of angry
      expressions was evident for other race faces. Kubota and Ito (2007) found a happy
      categorization advantage for both own race and other race faces. These results
      have vastly different implications for understanding the influence of race cues
      on the processing of emotional expressions. The current study replicates the
      results of both prior studies and indicates that face type (computer-generated
      vs. photographic), presentation duration, and especially stimulus set size
      influence the happy categorization advantage as well as the moderating effect of
      poser race.

PMID- 22642348
TI  - More than meets the eye: the role of self-identity in decoding complex emotional
      states.
AB  - Folk wisdom asserts that "the eyes are the window to the soul," and empirical
      science corroborates a prominent role for the eyes in the communication of
      emotion. Herein we examine variation in the ability to "read" the eyes of others
      as a function of social group membership, employing a widely used emotional state
      decoding task: "Reading the Mind in Eyes." This task has documented impaired
      emotional state decoding across racial groups, with cross-race performance on par
      with that previously reported as a function of autism spectrum disorders. The
      present study extended this work by examining the moderating role of social
      identity in such impairments. For college students more highly identified with
      their university, cross-race performance differences were not found for judgments
      of "same-school" eyes but remained for "rival-school" eyes. These findings
      suggest that impaired emotional state decoding across groups may thus be more
      amenable to remediation than previously realized.

PMID- 22642349
TI  - The temporal evolution of social sharing of emotions and its consequences on
      emotional recovery: a longitudinal study.
AB  - After an emotional episode individuals need to talk about their experiences in a
      repetitive process called social sharing of emotions. In the present study we
      adopted a longitudinal design over a 9-month period to achieve 2 main goals:
      First, we aimed to investigate the relationship between social sharing and
      recovery from an initial emotional experience; second, we tested a model of
      prediction of the perpetuation of social sharing over time. Findings confirm that
      social sharing is a common consequence of experiencing an emotion, regardless of
      participants' levels of education, which tends to diminish over time, leading to
      an increasing sense of recovery. The prolongation of social sharing is a
      maladaptive outcome of experiencing an emotion, and a poor recovery is a direct
      consequence of long-term self-perpetuating social sharing. The results have
      implications for the assessment of the role of both dispositional factors and
      characteristics of the eliciting event on the prolongation of social sharing of
      emotions.

PMID- 22642350
TI  - Reliable facial muscle activation enhances recognizability and credibility of
      emotional expression.
AB  - We tested Ekman's (2003) suggestion that movements of a small number of reliable
      facial muscles are particularly trustworthy cues to experienced emotion because
      they tend to be difficult to produce voluntarily. On the basis of theoretical
      predictions, we identified two subsets of facial action units (AUs): reliable AUs
      and versatile AUs. A survey on the controllability of facial AUs confirmed that
      reliable AUs indeed seem more difficult to control than versatile AUs, although
      the distinction between the two sets of AUs should be understood as a difference
      in degree of controllability rather than a discrete categorization. Professional
      actors enacted a series of emotional states using method acting techniques, and
      their facial expressions were rated by independent judges. The effect of the two
      subsets of AUs (reliable AUs and versatile AUs) on identification of the emotion
      conveyed, its perceived authenticity, and perceived intensity was investigated.
      Activation of the reliable AUs had a stronger effect than that of versatile AUs
      on the identification, perceived authenticity, and perceived intensity of the
      emotion expressed. We found little evidence, however, for specific links between
      individual AUs and particular emotion categories. We conclude that reliable AUs
      may indeed convey trustworthy information about emotional processes but that most
      of these AUs are likely to be shared by several emotions rather than providing
      information about specific emotions. This study also suggests that the issue of
      reliable facial muscles may generalize beyond the Duchenne smile.

PMID- 22642351
TI  - Music training and emotion comprehension in childhood.
AB  - Children and adults with music training score higher on tests of intellectual
      ability than their peers without training, but it is unclear whether music
      lessons are associated with social or emotional functioning. We examined whether
      music training in childhood is predictive of understanding emotions. We
      administered the Test of Emotion Comprehension (TEC) and a brief IQ test to
      musically trained and untrained 7- and 8-year-olds. Musically trained children
      scored higher on IQ and on the TEC even after accounting for demographic
      variables. Group differences in TEC scores disappeared, however, when IQ scores
      were held constant. These findings suggest that nonmusical associations with
      music training are limited to measures of intellectual ability and their
      correlates.

PMID- 22642352
TI  - Negative arousal amplifies the effects of saliency in short-term memory.
AB  - Evidence from 2 experiments suggests that negative arousal increases biases in
      attention that result from differences in visual salience. Participants were
      exposed to negative arousing or neutral sounds before briefly viewing an array of
      letters. They reported as many of the letters as they could, and attention was
      biased to certain letters by increasing salience through visual contrast.
      Regardless of the type of sound heard, participants were more likely to recall
      high-salience letters than low-salience letters. However, on arousing trials
      recall of high-salience letters increased, while recall of low-salience letters
      did not. These findings indicate that negative emotional arousal increases the
      selectivity of attention, and provides evidence for arousal-biased competition
      theory (Mather & Sutherland, 2011), which predicts that emotional arousal
      enhances representations of stimuli that have priority.

PMID- 22642353
TI  - Memory for time and place contributes to enhanced confidence in memories for
      emotional events.
AB  - Emotion strengthens the subjective sense of remembering. However, these
      confidently remembered emotional memories have not been found be more accurate
      for some types of contextual details. We investigated whether the subjective
      sense of recollecting negative stimuli is coupled with enhanced memory accuracy
      for three specific types of central contextual details using the remember/know
      paradigm and confidence ratings. Our results indicate that the subjective sense
      of remembering is indeed coupled with better recollection of spatial location and
      temporal context, but not higher memory accuracy for colored dots placed in the
      conceptual center of negative and neutral scenes. These findings show that the
      enhanced subjective recollective experience for negative stimuli reliably
      indicates objective recollection for spatial location and temporal context, but
      not for other types of details, whereas for neutral stimuli, the subjective sense
      of remembering is coupled with all the types of details assessed. Translating
      this finding to flashbulb memories, we found that, over time, more participants
      correctly remembered the location where they learned about the terrorist attacks
      on 9/11 than any other canonical feature. Likewise, participants' confidence was
      higher in their memory for location versus other canonical features. These
      findings indicate that the strong recollective experience of a negative event
      corresponds to an accurate memory for some kinds of contextual details but not
      for other kinds. This discrepancy provides further evidence that the subjective
      sense of remembering negative events is driven by a different mechanism than the
      subjective sense of remembering neutral events.

PMID- 22642354
TI  - Double dissociation: circadian off-peak times increase emotional reactivity;
      aging impairs emotion regulation via reappraisal.
AB  - This study explored how the effectiveness of specific emotion regulation
      strategies might be influenced by aging and by time of day, given that in older
      age the circadian peak in cognitive performance is earlier in the day. We
      compared the benefit gained by 40 older (60-78 years; 20 women) and 40 younger
      (18-30 years; 20 women) adults during either on-peak or off-peak circadian times
      on 2 specific types of cognitive emotion regulation strategies: distraction and
      reappraisal. Participants rated their negative emotional responses to negative
      and neutral images under 3 conditions: a baseline nonregulation condition, a
      distraction condition involving a working memory task, and a reappraisal
      condition that involved reinterpreting the situation displayed using specific
      preselected strategies. First, as hypothesized, there was a crossover interaction
      such that participants in each age group reported more negative reactivity at
      their off-peak time of day. Second, a double dissociation was observed as
      circadian rhythms affected only negative reactivity-with reactivity highest at
      off-peak times-and aging diminished reappraisal but not distraction ability or
      reactivity. These findings add to growing evidence that understanding the effects
      of aging on emotion and emotion regulation depends on taking both time of day and
      type of regulatory strategy into account.

PMID- 22642355
TI  - The dynamic interplay between emotions in daily life: augmentation, blunting, and
      the role of appraisal overlap.
AB  - Our emotions don't have lives of their own, but mutually influence each other
      across time. Augmentation and blunting occur when experience of a current emotion
      increases or decreases the experience of another, subsequent emotion, and play a
      role in many everyday phenomena. In this study, we investigated patterns of
      augmentation and blunting between the experience of anger, sadness, relaxation,
      and happiness in daily life. In general, emotions with similar (opposite) valence
      showed augmentation (blunting) from one moment to the next. In search for a
      possible underlying mechanism, we showed that strength of augmentation and
      blunting was a function of degree of idiosyncratic appraisal overlap between two
      emotional states. This occurred even to the point that emotions with similar
      valence blunted one another in cases of small overlap, and emotions with opposite
      valence augmented one another in cases of large overlap. The findings reveal the
      dynamic interplay between different emotions across time, and highlight the role
      of appraisal overlap therein.

PMID- 22642357
TI  - Mapping correspondence between facial mimicry and emotion recognition in healthy
      subjects.
AB  - We aimed at verifying the hypothesis that facial mimicry is causally and
      selectively involved in emotion recognition. For this purpose, in Experiment 1,
      we explored the effect of tonic contraction of muscles in upper or lower half of
      participants' face on their ability to recognize emotional facial expressions. We
      found that the "lower" manipulation specifically impaired recognition of
      happiness and disgust, the "upper" manipulation impaired recognition of anger,
      while both manipulations affected recognition of fear; recognition of surprise
      and sadness were not affected by either blocking manipulations. In Experiment 2,
      we verified whether emotion recognition is hampered by stimuli in which an upper
      or lower half-face showing an emotional expression is combined with a neutral
      half-face. We found that the neutral lower half-face interfered with recognition
      of happiness and disgust, whereas the neutral upper half impaired recognition of
      anger; recognition of fear and sadness was impaired by both manipulations,
      whereas recognition of surprise was not affected by either manipulation. Taken
      together, the present findings support simulation models of emotion recognition
      and provide insight into the role of mimicry in comprehension of others'
      emotional facial expressions.

PMID- 22642356
TI  - Age-related differences in emotional reactivity, regulation, and rejection
      sensitivity in adolescence.
AB  - Although adolescents' emotional lives are thought to be more turbulent than those
      of adults, it is unknown whether this difference is attributable to developmental
      changes in emotional reactivity or emotion regulation. Study 1 addressed this
      question by presenting healthy individuals aged 10-23 with negative and neutral
      pictures and asking them to respond naturally or use cognitive reappraisal to
      down-regulate their responses on a trial-by-trial basis. Results indicated that
      age exerted both linear and quadratic effects on regulation success but was
      unrelated to emotional reactivity. Study 2 replicated and extended these findings
      using a different reappraisal task and further showed that situational (i.e.,
      social vs. nonsocial stimuli) and dispositional (i.e., level of rejection
      sensitivity) social factors interacted with age to predict regulation success:
      young adolescents were less successful at regulating responses to social than to
      nonsocial stimuli, particularly if the adolescents were high in rejection
      sensitivity. Taken together, these results have important implications for the
      inclusion of emotion regulation in models of emotional and cognitive development.

PMID- 22642358
TI  - Emotions are real.
AB  - It is obvious that emotions are real, but the question is what kind of "real" are
      they? In this article, I outline a theoretical approach where emotions are a part
      of social reality. I propose that physical changes (in the face, voice, and body,
      or neural circuits for behavioral adaptations like freezing, fleeing, or
      fighting) transform into an emotion when those changes take on psychological
      functions that they cannot perform by their physical nature alone. This requires
      socially shared conceptual knowledge that perceivers use to create meaning from
      these physical changes (as well as the circuitry that supports this meaning
      making). My claim is that emotions are, at the same time, socially constructed
      and biologically evident. Only when we understand all the elements that construct
      emotional episodes, in social, psychological, and biological terms, will we
      understand the nature of emotion.

PMID- 22642360
TI  - Spin-assisted multilayers of poly(methyl methacrylate) and zinc oxide quantum
      dots for ultraviolet-blocking applications.
AB  - Thin UV-blocking films of poly(methyl methacrylate) (PMMA) and ZnO quantum dots
      (QDs) were built-up by spin-coating. Ellipsometry reveals average thicknesses of
      9.5 and 8.6 nm per bilayer before and after heating at 100  degrees C for one
      hour, respectively. The surface roughness measured by Atomic force microscopy
      (AFM) was 3.6 and 8.4 nm for the one and ten bilayer films, respectively. The
      linear increase in thickness as well as the low surface roughness increment per
      bilayer indicates a stratified multilayer structure and a smooth interface
      without aggregation. The absorption of UV radiation increased with increasing
      number of bilayers. At the same time, transmission was damped at wavelengths
      shorter than 375 nm. The thin films had a high and constant transparency in the
      visible region. Green-light emitting QDs could be detected by confocal microscopy
      at a concentration of 20% in a single layer of PMMA/ZnO. PMMA/ZnO QDs thin films
      are hydrophobic, as indicated by contact angle measurements. 

PMID- 22642362
TI  - Extracorporeal shock wave therapy (ESWT) for wound healing: technology,
      mechanisms, and clinical efficacy.
AB  - For almost 30 years, extracorporeal shock wave therapy has been clinically
      implemented as an effective treatment to disintegrate urinary stones. This
      technology has also emerged as an effective noninvasive treatment modality for
      several orthopedic and traumatic indications including problematic soft tissue
      wounds. Delayed/nonhealing or chronic wounds constitute a burden for each patient
      affected, significantly impairing quality of life. Intensive wound care is
      required, and this places an enormous burden on society in terms of lost
      productivity and healthcare costs. Therefore, cost-effective, noninvasive, and
      efficacious treatments are imperative to achieve both (accelerated and complete)
      healing of problematic wounds and reduce treatment-related costs. Several
      experimental and clinical studies show efficacy for extracorporeal shock wave
      therapy as means to accelerate tissue repair and regeneration in various wounds.
      However, the biomolecular mechanism by which this treatment modality exerts its
      therapeutic effects remains unclear. Potential mechanisms, which are discussed
      herein, include initial neovascularization with ensuing durable and functional
      angiogenesis. Furthermore, recruitment of mesenchymal stem cells, stimulated cell
      proliferation and differentiation, and anti-inflammatory and antimicrobial
      effects as well as suppression of nociception are considered important facets of
      the biological responses to therapeutic shock waves. This review aims to provide
      an overview of shock wave therapy, its history and development as well as its
      current place in clinical practice. Recent research advances are discussed
      emphasizing the role of extracorporeal shock wave therapy in soft tissue wound
      healing.

PMID- 22642361
TI  - Removal of the tag from His-tagged ILYd4, a human CD59 inhibitor, significantly
      improves its physical properties and its activity.
AB  - Complement dependent cytotoxicity (CDC) significantly contributes to Rituximab
      (RTX) and Ofatumumab (OFA) efficacies in the treatment of B-cell non-Hodgkin's
      lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Human CD59 (hCD59) is a
      key complement regulatory protein that restricts the formation of the membrane
      attack complex and thereby inhibits CDC. hCD59 is an important determinant of the
      sensitivity of NHL and CLL to RTX and OFA treatment. Recently, we developed a
      specific and potent hCD59 inhibitor, His-tagged ILYd4, which consists of 30 amino
      acid sequences extending from the N-terminus of ILYd4. Our previously published
      results indicate that His-tagged ILYd4 can be used as a lead candidate to further
      develop a potential therapeutic adjuvant for RTX and OFA treatment of RTX
      resistant NHL and CLL. However, these studies were conducted using ILYd4 tagged
      on the N-terminus with 30 additional amino acids (AA) containing 6 X His used for
      immobilized metal affinity chromatograph. As a further step towards the
      development of ILYd4-based therapeutics, we investigated the impact of the
      removal of this extraneous sequence on the anti-hCD59 activity. In this paper, we
      report the generation and characterization of tag-free ILYd4. We demonstrate that
      tag-free ILYd4 has over threefold higher anti-hCD59 activities than the His
      tagged ILYd4. The enhanced RTX-mediated CDC effect on B-cell malignant cells
      comes from tag-free ILYd4's improved functionality and physical properties
      including better solubility, reduced tendency to aggregation, and greater thermal
      stability. Therefore, tag-free ILYd4 is a better candidate for the further
      development for the clinical application.

PMID- 22642363
TI  - Bayesian data analysis of severe fatal accident risk in the oil chain.
AB  - We analyze the risk of severe fatal accidents causing five or more fatalities and
      for nine different activities covering the entire oil chain. Included are
      exploration and extraction, transport by different modes, refining and final end
      use in power plants, heating or gas stations. The risks are quantified separately
      for OECD and non-OECD countries and trends are calculated. Risk is analyzed by
      employing a Bayesian hierarchical model yielding analytical functions for both
      frequency (Poisson) and severity distributions (Generalized Pareto) as well as
      frequency trends. This approach addresses a key problem in risk estimation-namely
      the scarcity of data resulting in high uncertainties in particular for the risk
      of extreme events, where the risk is extrapolated beyond the historically most
      severe accidents. Bayesian data analysis allows the pooling of information from
      different data sets covering, for example, the different stages of the energy
      chains or different modes of transportation. In addition, it also inherently
      delivers a measure of uncertainty. This approach provides a framework, which
      comprehensively covers risk throughout the oil chain, allowing the allocation of
      risk in sustainability assessments. It also permits the progressive addition of
      new data to refine the risk estimates. Frequency, severity, and trends show
      substantial differences between the activities, emphasizing the need for detailed
      risk analysis.

PMID- 22642364
TI  - Brains, tools, innovation and biogeography in crows and ravens.
AB  - BACKGROUND: Crows and ravens (Passeriformes: Corvus) are large-brained birds with
      enhanced cognitive abilities relative to other birds. They are among the few non
      hominid organisms on Earth to be considered intelligent and well-known examples
      exist of several crow species having evolved innovative strategies and even use
      of tools in their search for food. The 40 Corvus species have also been
      successful dispersers and are distributed on most continents and in remote
      archipelagos. RESULTS: This study presents the first molecular phylogeny
      including all species and a number of subspecies within the genus Corvus. We date
      the phylogeny and determine ancestral areas to investigate historical
      biogeographical patterns of the crows. Additionally, we use data on brain size
      and a large database on innovative behaviour and tool use to test whether brain
      size (i) explains innovative behaviour and success in applying tools when
      foraging and (ii) has some correlative role in the success of colonization of
      islands. Our results demonstrate that crows originated in the Palaearctic in the
      Miocene from where they dispersed to North America and the Caribbean, Africa and
      Australasia. We find that relative brain size alone does not explain tool use,
      innovative feeding strategies and dispersal success within crows. CONCLUSIONS:
      Our study supports monophyly of the genus Corvus and further demonstrates the
      direction and timing of colonization from the area of origin in the Palaearctic
      to other continents and archipelagos. The Caribbean was probably colonized from
      North America, although some North American ancestor may have gone extinct, and
      the Pacific was colonized multiple times from Asia and Australia. We did not find
      a correlation between relative brain size, tool use, innovative feeding
      strategies and dispersal success. Hence, we propose that all crows and ravens
      have relatively large brains compared to other birds and thus the potential to be
      innovative if conditions and circumstances are right.

PMID- 22642365
TI  - Structure-activity relationship study of N6-(2-(4-(1H-Indol-5-yl)piperazin-1
      yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine analogues:
      development of highly selective D3 dopamine receptor agonists along with a highly
      potent D2/D3 agonist and their pharmacological characterization.
AB  - In our effort to develop multifunctional drugs against Parkinson's disease, a
      structure-activity-relationship study was carried out based on our hybrid
      molecular template targeting D2/D3 receptors. Competitive binding with
      [(3)H]spiroperidol was used to evaluate affinity (K(i)) of test compounds.
      Functional activity of selected compounds in stimulating [(35)S]GTPgammaS binding
      was assessed in CHO cells expressing either human D2 or D3 receptors. Our results
      demonstrated development of highly selective compounds for D3 receptor (for (-)
      40K(i), D3 = 1.84 nM, D2/D3 = 583.2; for (-)-45K(i), D3 = 1.09 nM, D2/D3 =
      827.5). Functional data identified (-)-40 (EC(50), D2 = 114 nM, D3 = 0.26 nM,
      D2/D3 = 438) as one of the highest D3 selective agonists known to date. In
      addition, high affinity, nonselective D3 agonist (-)-19 (EC(50), D2 = 2.96 nM and
      D3 = 1.26 nM) was also developed. Lead compounds with antioxidant activity were
      evaluated using an in vivo PD animal model.

PMID- 22642366
TI  - Aluminium tolerance of root hairs underlies genotypic differences in rhizosheath
      size of wheat (Triticum aestivum) grown on acid soil.
AB  - We found significant genetic variation in the ability of wheat (Triticum
      aestivum) to form rhizosheaths on acid soil and assessed whether differences in
      aluminium (Al(3+) ) tolerance of root hairs between genotypes was the
      physiological basis for this genetic variation. A method was developed to rapidly
      screen rhizosheath size in a range of wheat genotypes. Backcrossed populations
      were generated from cv Fronteira (large rhizosheath) using cv EGA-Burke (small
      rhizosheath) as the recurrent parent. A positive correlation existed between
      rhizosheath size on acid soil and root hair length. In hydroponic experiments,
      root hairs of the backcrossed lines with large rhizosheaths were more tolerant of
      Al(3+) toxicity than the backcrossed lines with small rhizosheaths. We conclude
      that greater Al(3+) tolerance of root hairs underlies the larger rhizosheath of
      wheat grown on acid soil. Tolerance of the root hairs to Al(3+) was largely
      independent of the TaALMT1 gene which suggests that different genes encode the
      Al(3+) tolerance of root hairs. The maintenance of longer root hairs in acid
      soils is important for the efficient uptake of water and nutrients.

PMID- 22642367
TI  - Heparin concentrations in neonates during cardiopulmonary bypass: a rebuttal.

PMID- 22642368
TI  - Synthesis of bispecific antibodies using genetically encoded unnatural amino
      acids.
AB  - Bispecific antibodies were constructed using genetically encoded unnatural amino
      acids with orthogonal chemical reactivity. A two-step process afforded
      homogeneous products in excellent yield. Using this approach, we synthesized an
      anti-HER2/anti-CD3 bispecific antibody, which efficiently cross-linked HER2+
      cells and CD3+ cells. In vitro effector-cell mediated cytotoxicity was observed
      at picomolar concentrations.

PMID- 22642369
TI  - Evaluation of the endotracheal tube cuff pressure resulting from four different
      methods of inflation in dogs.
AB  - OBJECTIVE: To evaluate the endotracheal tube cuff pressure achieved by four
      different inflation methods. STUDY DESIGN: Prospective clinical study. ANIMALS:
      Eighty client owned dogs. METHODS: After anaesthesia induction, endotracheal
      intubation was performed using plastic or silicone tubes. A clinician unaware of
      tube type inflated the cuff by simple digital palpation (method A), thereafter
      the cuff was deflated and inflated again by a second clinician who tried to
      reproduce a previously learned cuff pressure of between 19 and 24 mmHg (method
      B). During method C the cuff was inflated to the minimum occlusive volume at an
      airway pressure of 20 cm H(2) O, and in method D the cuff was incrementally
      deflated until an audible air leak could be heard from the oral cavity at an
      airway pressure of 25 cm H(2) O. For all the methods, an operator recorded the
      actual cuff pressure obtained using a manometer. Heart rate, respiratory rate and
      mean arterial pressure were monitored throughout the procedure. RESULTS: The mean
      inflation pressure for plastic tubes was 56 +/- 28 mmHg for method A, 20 +/- 9
      mmHg for method B, 35 +/- 32 mmHg for method C and 46 +/- 39 mmHg for method D.
      Pressures using silicone tubes were significantly higher than for plastic tubes,
      the mean registered pressures being 79 +/- 39, 33 +/- 16, 77 +/- 50 and 92 +/- 56
      mmHg for methods A, B, C and D. CONCLUSIONS AND CLINICAL RELEVANCE: None of the
      methods evaluated in this study can be considered effective for inflating the
      endotracheal tube cuff to within the optimal range when using silicone tubes.
      Direct measurement of the cuff pressure with a manometer is therefore
      recommended.

PMID- 22642370
TI  - Quality-of-life and psychosocial outcome following childhood arterial ischaemic
      stroke.
AB  - OBJECTIVES: This study investigates psychosocial outcome and quality-of-life in
      children who have experienced arterial ischaemic stroke (AIS), using a
      multidimensional and multi-perspective approach. It also examines the predictors
      of quality-of-life following childhood AIS. METHOD: Forty-nine children between 6
      18 years of age were recruited from a specialist childhood stroke clinic.
      Children, their parents and their teachers rated the child's quality-of-life.
      Questionnaires rating the child's self-esteem, behaviour and emotions were
      administered. Each child also underwent a neuropsychological assessment. RESULTS:
      The findings show that child-, parent- and teacher-rated health-related quality
      of-life (HRQoL) is significantly lower than comparative norms following childhood
      AIS, across all domains (physical, emotional, social, school and cognitive
      functioning). Predictors of HRQoL include neurological severity, executive
      function, self-esteem and family functioning. CONCLUSIONS: Improved screening,
      services and interventions are necessary to monitor longer-term outcome and
      provide support for children who have experienced AIS and their families.

PMID- 22642371
TI  - Virtual surgical planning: a novel aid to robot-assisted laparoscopic partial
      nephrectomy.
AB  - BACKGROUND AND PURPOSE: Incidental detection of small renal masses has
      significantly increased over the last two decades with the advent of cross
      sectional imaging. The shift in stage has been met with a shift in treatment
      modality because the preservation of renal parenchyma can prevent adverse
      outcomes. Robot-assisted laparoscopic partial nephrectomy (RALPN) needs
      significant surgeon expertise, and preoperative planning is imperative. PATIENTS
      AND METHODS: Between December 2010 and September 2011, virtual surgical planning
      (VSP) was used in consecutive patients with renal tumors that were suspicious for
      renal-cell carcinoma who were undergoing RALPN by a single surgeon. Three
      dimensional (3D) reconstructions were examined and manipulated preoperatively,
      and an operative plan formulated. Intraoperative anatomy and preoperative 3D
      reconstructions were compared in real time. RESULTS: A total of 10 patients
      underwent RALPN with preoperative VSP. Average patient age at intervention was
      54.6 years and average tumor size was 4.3 cm (range 1.7-7.5 cm). Tumor laterality
      was evenly distributed. Nephrometry score ranged from 5A to 10P, and final tumor
      pathology results revealed malignancy in 80%. No complications occurred
      intraoperatively, and an excellent correlation was noted between preoperative 3D
      reconstruction and intraoperative anatomy. All patients underwent a successful
      partial nephrectomy with no positive margins on final pathology results. Mean
      length of surgery was 232.9 minutes (range 156-435 min), and mean estimated blood
      loss was 370 mL (range 75-1800 mL). Warm ischemia time ranged from 20 to 50
      minutes (mean 33.9 min). Data regarding postoperative renal function were
      available for six patients with an average loss of function of 9.5% (range 2%
      17%). CONCLUSIONS: The implementation of this novel technology has significantly
      improved our ability to plan RALPN preoperatively. Tumor depth and complexity of
      tumor resection are assessed and the appropriate operative intervention and
      approach planned. Tumor proximity to vascular structures and collecting system
      were reliably predicted and therefore anticipated. Overall, these advantages
      created a safer surgical endeavor.

PMID- 22642372
TI  - Heat treatments modify the tribological properties of nickel boron coatings.
AB  - The effects of annealing temperature on the tribological properties of
      electroless nickel-boron coatings have been investigated. The coatings were
      annealed in a tube furnace under a flow (0.0094 N m(3)/min) of oxygen gas at
      temperatures of 250, 400, 550, and 700  degrees C for 3 h. Using scanning
      electron microscopy, images of the annealed coatings documented changes in
      surface morphology. From this it was seen that the higher annealing temperatures
      produced marked changes, moving from the nodular structure of nickel-boron
      coatings to a flaked surface morphology. The chemical effect of the annealing
      temperature was studied via X-ray photoelectron spectroscopy (XPS) and Raman
      spectroscopy. The XPS data indicated that after annealing at the temperatures of
      550 and 700  degrees C, an accumulation of boron oxide species could be seen at
      the surface as well as a complete loss of nickel signal. An analysis of Raman
      spectra collected across the surface further identified the predominant species
      to be boric acid. The tribological response of the coatings was studied with a
      pin-on-disk tribometer with 440C stainless steel balls run against the coatings
      in ambient air. It was seen that the as received sample and the sample annealed
      at 250  degrees C samples exhibited modest friction properties, while the 400 
      degrees C sample had increased friction due to wear debris from the ball. The 550
      and 700  degrees C samples showed remarkably low friction coefficients between
      0.06 and 0.08, attributable to the presence of boric acid. The wear tracks were
      analyzed using scanning white light interferometry and from this data wear rates
      were obtained for the coatings ranging from 10(-8) to 10(-7) mm(3)/Nm. 

PMID- 22642373
TI  - Sensorimotor resonance is an outcome but not a platform to anticipating harm to
      others.
AB  - When perceiving imminent harm to others, quickly detecting potential hazards to
      oneself should be vital. In this case, mirroring the outcome of observed actions
      appears paradoxical. This study measured electroencephalographic/event-related
      potentials and mu suppression that were induced by dynamic animations; each
      animation was composed of three consecutive pictures depicting an individual
      being accidentally injured. The results indicated that the first picture evoked
      frontal N260 and central N360, the possible brain source of which is estimated in
      the dorsolateral prefrontal cortex, and the third picture elicited late positive
      potentials, the possible sources of which might be generated from the insular and
      mid-cingulate cortex. Differential mu suppression, in relation to the
      sensorimotor resonance of empathy for pain, is associated with the third picture
      containing the crucial affective valence, but not with the first picture. The
      masking procedure on the third picture attenuated this mu suppression. Mediation
      analysis further confirmed that sensorimotor resonance is not a significant
      mediator in predicting subjective unpleasantness for observed actions. The
      findings suggest that sensorimotor resonance is not a platform, but rather an
      outcome when anticipating harm to others.

PMID- 22642374
TI  - Copper-free click biofunctionalization of silicon nitride surfaces via strain
      promoted alkyne-azide cycloaddition reactions.
AB  - Cu-free "click" chemistry is explored on silicon nitride (Si(3)N(4)) surfaces as
      an effective way for oriented immobilization of biomolecules. An omega
      unsaturated ester was grafted onto Si(3)N(4) using UV irradiation. Hydrolysis
      followed by carbodiimide-mediated activation yielded surface-bound active
      succinimidyl and pentafluorophenyl ester groups. These reactive surfaces were
      employed for the attachment of bicyclononyne with an amine spacer, which
      subsequently enabled room temperature strain-promoted azide-alkyne cycloaddition
      (SPAAC). This stepwise approach was characterized by means of static water
      contact angle, X-ray photoelectron spectroscopy, and fluorescence microscopy. The
      surface-bound SPAAC reaction was studied with both a fluorine-tagged azide and an
      azide-linked lactose, yielding hydrophobic and bioactive surfaces for which the
      presence of trace amounts of Cu ions would have been problematic. Additionally,
      patterning of the Si(3)N(4) surface using this metal-free click reaction with a
      fluorescent azide is shown. These results demonstrate the ability of the SPAAC as
      a generic tool for anchoring complex molecules onto a surface under extremely
      mild, namely ambient and metal-free, conditions in a clean and relatively fast
      manner.

PMID- 22642375
TI  - Frequency shifts in SERS for biosensing.
AB  - We report an observation of a peculiar effect in which the vibrational
      frequencies of antibody-conjugated SERS-active reporter molecules are shifted in
      quantitative correlation with the concentration of the targeted antigen. We
      attribute the frequency shifts to mechanical perturbations in the antibody
      reporter complex, as a result of antibody-antigen interaction forces. Our
      observation thus demonstrates the potentiality of an antibody-conjugated SERS
      active reporter complex as a SERS-active nanomechanical sensor for biodetection.
      Remarkably, our sensing scheme, despite employing only one antibody, was found to
      be able to achieve detection sensitivity comparable to that of a conventional
      sandwich immunoassay. Additionally, we have carried out a proof-of-concept study
      into using multiple "stress-sensitive" SERS reporters for multiplexed detection
      of antigen-antibody bindings at the subdiffraction limit. The current work could
      therefore pave the way to realizing a label-free high-density protein nanoarray.

PMID- 22642376
TI  - Antipathogenic properties of Lactobacillus plantarum on Pseudomonas aeruginosa:
      the potential use of its supernatants in the treatment of infected chronic
      wounds.
AB  - Pathogenic bacteria delay wound healing through several different mechanisms such
      as persistent production of inflammatory mediators or maintenance of necrotic
      neutrophils, which release cytolytic enzymes and free oxygen radicals. One of the
      most frequent pathogens isolated from infections in chronic wounds is Pseudomonas
      aeruginosa. This bacterium is extremely refractory to therapy and to host immune
      attack when it forms biofilms. Therefore, antibiotics and antiseptics are
      becoming useless in the treatment of these infections. In previous works, we
      demonstrated that Lactobacillus plantarum has an important antipathogenic
      capacity on P. aeruginosa. The aim of the present work was to elucidate the
      mechanism involved in the control of growth of P. aeruginosa on different
      surfaces by L. plantarum. For this purpose, we investigated the effects of L.
      plantarum supernatants on pathogenic properties of P. aeruginosa, such as
      adhesion, viability, virulence factors, biofilm formation, and quorum sensing
      signal expression. L. plantarum supernatants were able to inhibit pathogenic
      properties of P. aeruginosa by a quorum quenching mechanism. The antipathogenic
      properties mentioned above, together with the immunomodulatory, tissue repair,
      and angiogenesis properties in the supernatants of L. plantarum, make them an
      attractive option in infected chronic wound treatment.

PMID- 22642377
TI  - Genetic components to belowground carbon fluxes in a riparian forest ecosystem: a
      common garden approach.
AB  - Soil carbon dioxide (CO(2)) efflux is a major component of terrestrial carbon (C)
      cycles; yet, the demonstration of covariation between overstory tree genetic
      based traits and soil C flux remains a major frontier in understanding biological
      controls over soil C. Here, we used a common garden with two native tree species,
      Populus fremontii and P. angustifolia, and their naturally occurring hybrids to
      test the predictability of belowground C fluxes on the basis of taxonomic
      identity and genetic marker composition of replicated clones of individual
      genotypes. Three patterns emerged: soil CO(2) efflux and ratios of belowground
      flux to aboveground productivity differ by as much as 50-150% as a result of
      differences in clone identity and cross type; on the basis of Mantel tests of
      molecular marker matrices, we found that c. 30% of this variation was genetically
      based, in which genetically similar trees support more similar soil CO(2) efflux
      under their canopies than do genetically dissimilar trees; and the patterns
      detected in an experimental garden match observations in the wild, and seem to be
      unrelated to measured abiotic factors. Our findings suggest that the genetic
      makeup of the plants growing on soil has a significant influence on the release
      of C from soils to the atmosphere.

PMID- 22642379
TI  - Observations of the potency and duration of vecuronium in isoflurane-anesthetized
      horses.
AB  - OBJECTIVE: To evaluate the potency and duration of three subparalyzing doses of
      vecuronium (VEC) in isoflurane-anesthetized horses. STUDY DESIGN: Prospective
      experimental study. ANIMALS: Thirteen healthy adult horses undergoing
      arthroscopic surgery. METHODS: During isoflurane anesthesia, horses received one
      of three doses of vecuronium (25, 50, or 100 MUg kg(-1)). Neuromuscular
      transmission was monitored with acceleromyography (AMG) with train-of-four (TOF)
      stimulation of the radial nerve. Maximal depression of the first twitch (T1), and
      onset time were recorded for each dose. Recovery time to a TOF ratio >90% was
      also evaluated. RESULTS: Vecuronium 25 MUg kg(-1) produced no observable T1
      depression in four horses. VEC 50 MUg kg(-1) (n = 5) produced a maximal T1
      depression of [median (min, max)] 41 (20, 71) % in four horses, and no
      neuromuscular block was seen in the fifth. VEC 100 MUg kg(-1) was given to four
      horses and produced a T1 depression of 73 (64, 78) %. Of the four horses in which
      VEC 50 MUg kg(-1) produced a measurable neuromuscular block, three recovered
      spontaneously 43 (40, 52) minutes after VEC administration; a fourth subject
      received edrophonium to reverse residual block at the end of the surgery.
      Spontaneous recovery after VEC 100 MUg kg(-1) occurred by 112 minutes in one
      horse, and had to be facilitated by edrophonium in the remaining three horses,
      more than 2 hours after VEC had been given. CONCLUSIONS AND CLINICAL RELEVANCE: A
      dose of 100 MUg kg(-1) VEC in isoflurane anesthetized horses failed to produce
      complete paralysis. The partial neuromuscular block lasted at least 2 hours after
      this dose had been administered. Edrophonium was required to reverse the
      neuromuscular block in three of four horses. It is likely that more than 100 MUg
      kg(-1) VEC would be necessary for complete neuromuscular blockade in horses, and
      that this dose will last >2 hours.

PMID- 22642378
TI  - Plasticity of DNA methylation in mouse T cell activation and differentiation.
AB  - BACKGROUND: Circulating CD4+ T helper cells are activated through interactions
      with antigen presenting cells and undergo differentiation into specific T helper
      cell subsets depending on the type of antigen encountered. In addition, the
      relative composition of the circulating CD4+ T cell population changes as animals
      mature with an increased percentage of the population being memory/effector type
      cells. RESULTS: Here, we report on the highly plastic nature of DNA methylation
      at the genome-wide level as T cells undergo activation, differentiation and
      aging. Of particular note were the findings that DNA demethylation occurred
      rapidly following T cell activation and that all differentiated T cell
      populations displayed lower levels of global methylation than the non
      differentiated population. In addition, T cells from older mice had a reduced
      level of DNA methylation, most likely explained by the increase in the
      memory/effector cell fraction. Although significant genome-wide changes were
      observed, changes in DNA methylation at individual genes were restricted to
      specific cell types. Changes in the expression of enzymes involved in DNA
      methylation and demethylation reflect in most cases the changes observed in the
      genome-wide DNA methylation status. CONCLUSION: We have demonstrated that DNA
      methylation is dynamic and flexible in CD4+ T cells and changes rapidly both in a
      genome-wide and in a targeted manner during T cell activation, differentiation.
      These changes are accompanied by parallel changes in the enzymatic complexes that
      have been implicated in DNA methylation and demethylation implying that the
      balance between these opposing activities may play a role in the maintaining the
      methylation profile of a given cell type but also allow flexibility in a cell
      population that needs to respond rapidly to environmental signals.

PMID- 22642381
TI  - Absolute structures of monoterpenoids with a delta-lactone-containing skeleton
      from Ligularia hodgsonii.
AB  - Bioactivity-directed fractionation of a methanol extract of Ligularia hodgsonii
      afforded two new monoterpenoids, liguhodgcins A (1) and B (2), with an unusual
      delta-lactone-containing skeleton. Moreover, liguhodgcin A (1) contained a
      chlorine atom. The structures and absolute configurations of the two compounds
      were elucidated using NMR spectroscopy, X-ray crystallography, ECD data, and
      computational approaches. A probable biosynthesis pathway to 1 and 2 was also
      proposed and discussed. The cytotoxicity of compounds 1 and 2 was evaluated
      against the human leukemia (HL-60), human hepatoma (SMMC-7721), and human
      cervical carcinoma (HeLa) cell lines.

PMID- 22642380
TI  - Contribution of platelet vs. endothelial VWF to platelet adhesion and hemostasis.
AB  - BACKGROUND: von Willebrand factor (VWF) is a glycoprotein that plays an important
      role in primary hemostasis. VWF is synthesized and stored in endothelial cells
      (ECs) and megakaryocytes/platelets. Plasma VWF is primarily derived from ECs and
      is generally believed to be essential for hemostasis. VWF synthesized in
      megakaryocytes is stored in platelet alpha-granules, from which it is released
      following platelet activation. The relative contribution of VWF stored in ECs or
      megakaryocytes/platelets or present in plasma to hemostasis is not clear.
      OBJECTIVES: We investigated whether EC-derived VWF plays the major role in
      hemostasis while the contribution of platelet-derived VWF is negligible, or if
      platelet-derived VWF also significantly contributes to hemostasis. METHODS AND
      RESULTS: Mice expressing VWF only in ECs (EC-VWF) or platelets (Plt-VWF) were
      created by reciprocal bone marrow transplantation between C57BL/6J (WT) and VWF
      knockout mice (VWF-/-). Plasma VWF levels in EC-VWF were similar to WT. Plt-VWF
      mice had a trace amount of VWF in their plasma while VWF levels in platelet
      lysate were comparable to WT. Tail bleeding time was normal in EC-VWF.
      Interestingly, Plt-VWF showed partially corrected bleeding time and significantly
      decreased blood loss volume compared with VWF-/-. Adhesion of platelets perfused
      over immobilized collagen under shear stress was significantly higher in both EC
      VWF and Plt-VWF compared with VWF-/-. CONCLUSION: VWF synthesized in ECs is
      sufficient to support hemostasis in VWF-/- mice, and VWF produced in
      megakaryocytes/platelets can also contribute to hemostasis in the absence of EC
      derived VWF.

PMID- 22642382
TI  - Inference in conversation of adults with traumatic brain injury.
AB  - OBJECTIVE: To examine elaborative and automatic linguistic inferences in
      conversations between adults with and without traumatic brain injury (TBI) and
      their frequent communication partners. DESIGN AND METHODS: Participants with TBI
      were four female and three male adults and seven female communication partners.
      Comparison peers were two males and five females and one male and six female
      communication partners. Each participant completed 20-minute video-recorded
      conversation with his or her frequent communication partner. Conversations were
      transcribed, implicatures were identified and the percentage of correct
      inferences was determined. Inferences were categorized as automatic or
      elaborative and as missed or understood. RESULTS: Participants in both groups
      made significantly more errors on elaborative inferences than automatic
      inferences and participants with TBI made significantly more elaborative
      inference errors than comparison peers. There was no significant between-groups
      difference in error rates for automatic inferences. CONCLUSIONS: Individuals with
      TBI may show impairments in social language skills not only on standardized tests
      but also in everyday conversations. This may contribute to everyday partners'
      perceptions of social communication problems in adults with TBI.

PMID- 22642383
TI  - Isolation of bacterial strains able to metabolize lignin from screening of
      environmental samples.
AB  - AIMS: To develop a method to detect bacteria from environmental samples that are
      able to metabolize lignin. METHODS AND RESULTS: A previously developed UV-vis
      assay method for lignin degradation activity has been developed for use as a
      spray assay on agar plates. Nine mesophilic strains were isolated using this
      method from woodland soil incubated in enrichment cultures containing wheat straw
      lignocellulose: four Microbacterium isolates, two Micrococcus isolates,
      Rhodococcus erythropolis (all Actinobacteria) and two Ochrobactrum isolates
      (Alphaproteobacteria). Three thermotolerant isolates were isolated from the same
      screening method applied at 45 degrees C to samples of composted wheat straw from
      solid-state fermentation: Thermobifida fusca and two isolates related to
      uncharacterized species of Rhizobiales and Sphingobacterium (Bacteroidetes), the
      latter strain showing tenfold higher lignin degradation activity than other
      isolates. The isolated strains were able to depolymerize samples of size
      fractionated high molecular weight and low molecular weight Kraft lignin, and
      produced low molecular weight metabolites oxalic acid and protocatechuic acid
      from incubations containing wheat straw lignocellulose. CONCLUSIONS: A new method
      for the isolation of bacteria able to metabolize lignin has been developed, which
      has been used to identify 12 bacterial isolates from environmental sources. The
      majority of isolates cluster into the Actinobacteria and the Alphaproteobacteria.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Lignin-degrading bacterial strains could be
      used to convert lignin-containing feedstocks into renewable chemicals and to
      identify new bacterial lignin-degrading enzymes.

PMID- 22642384
TI  - What is your diagnosis? Cerebrospinal fluid from a dog.

PMID- 22642385
TI  - Rhenium-188: availability from the (188)W/(188)Re generator and status of current
      applications.
AB  - Rhenium-188 is one of the most readily available generator derived and useful
      radionuclides for therapy emitting beta(-) particles (2.12 MeV, 71.1% and 1.965
      MeV, 25.6%) and imageable gammas (155 keV, 15.1%). The (188)W/(188)Re generator
      is an ideal source for the long term (4-6 months) continuous availability of no
      carrier added (nca) (188)Re suitable for the preparation of radiopharmaceuticals
      for radionuclide therapy. The challenges associated with the double neutron
      capture route of production of the parent (188)W radionuclide have been a major
      impediment in the progress of application of (188)Re. Tungsten-188 of adequate
      specific activity can be prepared only in 2-3 of the high flux reactors operating
      in the World. Several useful technologies have been developed for the preparation
      of clinical grade (188)W/(188)Re generators. Since the specific activity of
      (188)W used in the generator is relatively low 185 GBq( < 5 Ci)/g], the eluted
      (188)ReO(4)(-) can have low radioactive concentration often insufficient for
      radiopharmaceutical preparation. However, several efficient post elution
      concentration techniques have been developed that yield clinically useful
      (188)ReO(4)(-) solutions. Rhenium-188 has been used for the preparation of
      therapeutic radiopharmaceuticals for the management of diseases such as bone
      metastasis, rheumatoid arthritis and primary cancers. Several early phase
      clinical studies using radiopharmaceuticals based on (188)Re-labeled
      phosphonates, antibodies, peptides, lipiodol and particulates have been reported.
      This article reviews the availability and use of (188)Re including a discussion
      of why broader use of (188)Re has not progressed as expected as a popular
      radionuclide for therapy.

PMID- 22642386
TI  - Electrochemical separation is an attractive strategy for development of
      radionuclide generators for medical applications.
AB  - Electrochemical separation techniques are not widely used in radionuclide
      generator technology and only a few studies have been reported [1-4].
      Nevertheless, this strategy is useful when other parent-daughter separation
      techniques are not effective or not possible. Such situations are frequent when
      low specific activity (LSA) parent radionuclides are used for instance with
      adsorption chromatographic separations, which can result in lower concentration
      of the daughter radionuclide in the eluent. In addition, radiation instability of
      the column matrix in many cases can affect the performance of the generator when
      long lived parent radionuclides are used. Intricate knowledge of the chemistry
      involved in the electrochemical separation is crucial to develop a reproducible
      technology that ensures that the pure daughter radionuclide can be obtained in a
      reasonable time of operation. Crucial parameters to be critically optimized
      include the applied potential, choice of electrolyte, selection of electrodes,
      temperature of electrolyte bath and the time of electrolysis in order to ensure
      that the daughter radionuclide can be reproducibly recovered in high yields and
      high purity. The successful electrochemical generator technologies which have
      been developed and are discussed in this paper include the (90)Sr/(90)Y,
      (188)W/(188)Re and (99)Mo/(99m)Tc generators. Electrochemical separation not only
      acts as a separation technique but also is an effective concentration methodology
      which yields high radioactive concentrations of the daughter products. The lower
      consumption of reagents and minimal generation of radioactive wastes using such
      electrochemical techniques are compatible with 'green chemistry' principles.

PMID- 22642387
TI  - Technetium-99m -- new production and processing strategies to provide adequate
      levels for SPECT imaging.
AB  - The most important radioisotope for use in Nuclear Medicine is (99m)Tc, supplied
      in the form of a (99)Mo/(99m)Tc generator. After the supply crisis of (99)Mo
      starting in 2008 the availability of (99)Mo became a worldwide concern. The
      purpose of this work is to do a brief story of the availability of (99)Mo in the
      world followed by an overview of the production routes of (99)Mo and the
      generators technology.

PMID- 22642388
TI  - Scandium-44: benefits of a long-lived PET radionuclide available from the
      (44)Ti/(44)Sc generator system.
AB  - (44)Ti/(44)Sc radionuclide generators are of interest for molecular imaging. The
      3.97 hours half-life of (44)Sc and its high positron branching of 94.27% may
      stimulate the application of (44)Sc-labeled PET radiopharmaceuticals. This review
      describes the current status of (44)Ti production, (44)Ti/(44)Sc radionuclide
      generator development, post-processing of generator eluates towards medical
      application, identification of ligands adequate to Sc(III) co-ordination
      chemistry, proof-of-principle labeling of (44)Sc-DOTA-octreotides, investigation
      of in vitro and in vivo parameters, and initial applications for molecular
      imaging - both in small animals and humans.

PMID- 22642389
TI  - Gallium-68 -- a new opportunity for PET available from a long shelf-life
      generator - automation and applications.
AB  - (68)Ge/(68)Ga generators have received tremendous attention in the last years
      based on the success of (68)Ga-labelled Somatostatin analogues for Positron
      Emission Tomography (PET), which are today used routinely worldwide. Various
      commercially available generator types are based on different column matrices
      including TiO(2), SnO(2) or organic (68)Gechelate coated silica, providing (68)Ga
      as Ga(3+) in HCl for radiolabeling procedures. These systems can serve as a
      stable source of (68)Ga for PET applications over periods of more than one year
      with high yields. A number of methods for post processing of the eluate including
      fractionation, anion or cation exchange purification have been developed. These
      methods are particularly important for high specific activity labeling of
      biomolecules such as peptides ensuring small volumes, low metallic contamination
      and low (68)Ge breakthrough. These systems have been implemented into fully
      automated modules allowing generator elution, post processing radiolabeling and
      formulation, complying with high regulatory demands. Quality aspects regarding
      the clinical use of (68)Ga for patient applications including limit of (68)Ge
      content, metal contamination, microbiological safety and radiochemical purity
      have been addressed. Overall, the establishment of (68)Ge/(68)Ga generator
      technology together with the development of novel (68)Ga-radiopharmaceuticals
      make (68)Ga a most promising radionuclide for PET in the years to come.

PMID- 22642390
TI  - Bismuth-213 and actinium-225 -- generator performance and evolving therapeutic
      applications of two generator-derived alpha-emitting radioisotopes.
AB  - The alpha emitters (225)Ac and (213)Bi are promising therapeutic radionuclides
      for application in targeted alpha therapy of cancer and infectious diseases. Both
      alpha emitters are available with high specific activity from established
      radionuclide generators. Their favourable chemical and physical properties have
      led to the conduction of a large number of preclinical studies and several
      clinical trials, demonstrating the feasibility, safety and therapeutic efficacy
      of targeted alpha therapy with (225)Ac and (213)Bi. This review describes methods
      for the production of (225)Ac and (213)Bi and gives an overview of
      (225)Ac/(213)Bi radionuclide generator systems. Selected preclinical studies are
      highlighted and the current clinical experience with (225)Ac and (213)Bi is
      summarized.

PMID- 22642391
TI  - Plasma treatment of polystyrene thin films affects more than the surface.
AB  - Plasma treatment of polymer materials introduces chemical functionalities and
      modifies the material to make the native hydrophobic surface more hydrophilic. It
      is generally assumed that this process only affects the surface of the material.
      We used vibrationally resonant sum-frequency generation spectroscopy to observe
      changes in the orientation of phenyl groups in polystyrene (PS) thin films on
      various substrates before and after plasma treatment. VR-SFG selectively probes
      regions of broken symmetry, such as surfaces, but can also detect the emergence
      of anisotropy. On dielectric substrates, such as fused silica, the spectroscopic
      peak corresponding to the symmetric stretching (nu2) mode of the phenyl rings was
      undetectable after plasma treatment, showing that surface phenyl rings were
      altered. This peak also diminished on conducting substrates, but the intensity of
      another peak corresponding to the same mode in a bulklike environment increased
      significantly, suggesting that plasma treatment induces partial ordering of the
      bulk polymer. This ordering is seen on conducting substrates even when the
      polymer is not directly exposed to the plasma. Annealing reverses these effects
      on the polystyrene bulk; however, the surface phenyl rings do not return to the
      orientation observed for untreated films. These results call into question the
      assumption that the effects of plasma treatment are limited to the free surface
      and opens up other possibilities for material modification with low-temperature
      plasmas. 

PMID- 22642392
TI  - Do apolipoprotein E genotype and educational attainment predict the rate of
      cognitive decline in normal aging? A 12-year follow-up of the Maastricht Aging
      Study.
AB  - OBJECTIVE: We investigated suspected longitudinal interaction effects of
      apolipoprotein E (APOE) genotype and educational attainment on cognitive decline
      in normal aging. METHOD: Our sample consisted of 571 healthy, nondemented adults
      aged between 49 and 82 years. Linear mixed-models analyses were performed with
      four measurement time points: baseline, 3-year, 6-year, and 12-year follow-up.
      Covariates included age at baseline, sex, and self-perceived physical and mental
      health. Dependent measures were global cognitive functioning (Mini-Mental State
      Examination; Folstein, Folstein, & McHugh, 1975), Stroop performance (Stroop
      Color-Word Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006a), set
      shifting performance (Concept Shifting Test; Van der Elst, Van Boxtel, Van
      Breukelen, & Jolles, 2006b), cognitive speed (Letter-Digit Substitution Test; Van
      der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006c), verbal learning (Verbal
      Learning Test: Sum of five trials; Van der Elst, Van Boxtel, Van Breukelen, &
      Jolles, 2005), and long-term memory (Verbal Learning Test: Delayed recall).
      RESULTS: We found only faint evidence that older, high-educated carriers of the
      APOE-epsilon4 allele (irrespective of zygosity) show a more pronounced decline
      than younger, low-educated carriers and noncarriers (irrespective of educational
      attainment). Moreover, this outcome was confined to concept-shifting performance
      and was especially observable between 6- and 12-year follow-ups. No protective
      effects of higher education were found on any of the six cognitive measures.
      CONCLUSIONS: We conclude that the combination of APOE-epsilon4 allele and high
      educational attainment may be a risk factor for accelerated cognitive decline in
      older age, as has been reported before, but only to a very limited extent.
      Moreover, we conclude that, within the cognitive reserve framework, education
      does not have significant protective power against age-related cognitive decline.

PMID- 22642393
TI  - Reliability and validity of the Virtual Reality Lateralized Attention Test in
      assessing hemispatial neglect in right-hemisphere stroke.
AB  - OBJECTIVE: Many tests of hemispatial neglect are insensitive to subtle (but
      clinically relevant) forms of the disorder. This study provides additional
      reliability and validity data on the Virtual Reality Lateralized Attention Test
      (VRLAT), an easy-to-administer computerized measure of hemispatial neglect that
      mimics the attentional demands of real-world tasks, and has previously shown
      strong validity and sensitivity (Dawson, Buxbaum, & Rizzo, 2008). The present
      study assessed a large sample of patients with the aim of developing a clinically
      useful version of the test, and established the concurrent criterion validity of
      the VRLAT as measured by its association with performance in a real-world task.
      METHOD: Seventy consecutively recruited right-hemisphere stroke patients were
      assessed with the VRLAT, which requires participants to name objects as they
      navigate (or are navigated) along a winding virtual path. They also performed a
      real-world navigation task, tests of sensory and motor function, and paper-and
      pencil neglect tests. RESULTS: The VRLAT demonstrated strong sensitivity and
      specificity, minimal practice effects, and strong validity, and outperformed
      traditional paper-and-pencil tests in the prediction of real-world collisions.
      CONCLUSIONS: The VRLAT is a sensitive, valid, and reliable measure of hemispatial
      neglect that requires no specialized equipment, is easy to administer, and is
      useful for both clinical and research purposes. Moreover, a shortened version
      with a 5-min administration time has many of the desirable psychometric
      properties of the original full-length task.

PMID- 22642394
TI  - Habit and recollection in healthy aging, mild cognitive impairment, and
      Alzheimer's disease.
AB  - OBJECTIVES: This study aimed to create a new French version of the Hay and Jacoby
      habit-training procedure (1996; 1999) and apply it to novel populations to
      determine the degree to which habit and recollection were affected. METHOD: 36
      young, 32 middle-aged, and 37 older adults participated in Experiment 1. 17
      controls, 17 patients with amnestic Mild Cognitive Impairment (a-MCI), and 17
      patients with Alzheimer's disease (AD) were involved in Experiment 2.
      Participants were assessed across a variety of demographic, neuropsychological
      and psychopathological variables (e.g., depressive affects, subjective experience
      of cognitive failures, interference sensitivity). The habit-training process
      dissociation was used to explore the cognitive mechanisms underlying memory slips
      to separate the contribution of habit and recollection to memory performance.
      RESULTS: The data show a very clear pattern of decreased recollection with age,
      F(2, 102) = 25.12, p < .001, eta2(p) = .197, and age-related neurological
      impairment, F(2, 48) = 39.22, p < .001, eta2(p) = .62, with intact use of habit
      based memory. Additional evidence for the validity of the process estimates is
      provided by theoretically meaningful correlations between the process estimates
      and measures of attentional control (Stroop test: r = -0.40) and subjective
      memory complaint (r = -0.45). CONCLUSIONS: Although likely not the same as
      familiarity, the data add to a growing literature suggesting that controlled
      forms of memory decline with age and in age-related neurological conditions (MCI
      and AD) whereas more automatic forms of memory (habit) remain intact. This
      research should improve understanding of memory complaints, preclinical and
      clinical dementia, and help target processes for rehabilitation.

PMID- 22642395
TI  - Penetration study of formulated nanosized titanium dioxide in models of damaged
      and sun-irradiated skins.
AB  - Inorganic ultraviolet filters such as titanium dioxide (TiO(2)), safe to use on
      healthy skin, are often applied on compromised and irradiated skin. The aim of
      this study was to evaluate in vitro the cutaneous penetration of TiO(2)
      nanoparticles (>=20 nm primary size), included in a sunscreen, in intact,
      damaged, irradiated, and damaged/irradiated pigskin. Cutaneous penetration and
      localization of TiO(2) after a 24-h sunscreen application were investigated
      quantitatively using inductively coupled plasma-mass spectrometry, and
      qualitatively using transmission electron microscopy (TEM). Elemental identity of
      the nanoparticles was evaluated by TEM-coupled Energy Dispersive X-ray analysis
      (TEM-EDX). In intact and damaged/irradiated skins, 102.35+/-4.20% and 102.84+/
      5.67% of the titanium deposited, respectively, were found at the surface and
      stratum corneum (SC), whereas only 0.19+/-0.15% and 0.39+/-0.39% were found in
      the viable epidermis and dermis and no titanium was detected in the receptor
      fluid. TEM-EDX analysis confirmed the presence of titanium in the aggregates
      formed by TiO(2) at the SC surface, as already characterized in the sunscreen
      formulation. TiO(2) nanoparticles included in a sunscreen thus remain in the
      uppermost layers of the SC, whether in intact skin or in compromised and/or skin
      exposed to simulated solar radiation.

PMID- 22642396
TI  - The effect of stereotypical primes on the neural processing of racially ambiguous
      faces.
AB  - Previous research has demonstrated that an early attentional component of the
      event-related potential (ERP), the P2, is sensitive to the distinction between
      the processing of racial outgroup and ingroup faces but may not be sensitive to
      the distinction between racially ambiguous and ingroup faces. Recent behavioral
      work, however, has suggested that contextual information may affect the
      processing of racially ambiguous faces. Thus, the first goal of this study was to
      examine whether the early neural processing of racially ambiguous faces would be
      affected by primed stereotypes. White college student participants (n = 29)
      completed a task in which they racially categorized monoracial Black and White
      faces and racially ambiguous Black-White morphs. These faces were preceded by
      positive and negative Black and White stereotypical primes. Results indicated
      that P2 amplitude to the racially ambiguous faces was moderated by the valence of
      the primes such that negative primes led to greater neural processing of the
      racially ambiguous faces than positive primes. Furthermore, the extent to which
      P2 amplitude was affected by prime valence was moderated by individual
      differences in preference for structure and categorical thinking, as well as
      comfort with ambiguity.

PMID- 22642397
TI  - Fundamentals of randomized clinical trials in wound care: design and conduct.
AB  - The care for chronic and acute wounds is a substantial problem around the world.
      This has led to a plethora of products to accelerate healing. Unfortunately, the
      quality of studies evaluating the efficacy of such wound care products is
      frequently low. Randomized clinical trials are universally acknowledged as the
      study design of choice for comparing treatment effects, as they eliminate several
      sources of bias. We propose a framework for the design and conduct of future
      randomized clinical trials that will offer strong scientific evidence for the
      effectiveness of wound care interventions. While randomization is a necessary
      feature of a robust comparative study, it is not sufficient to ensure a study at
      low risk of bias. Randomized clinical trials should also ensure adequate
      allocation concealment and blinding of outcome assessors, apply intention-to
      treat analysis, and use patient-oriented outcomes. This article proposes
      strategies for improving the evidence base for wound care decision making.

PMID- 22642398
TI  - Gene networks modified by sulphonylureas in beta cells: a pathway-based analysis
      of insulin secretion and cell death.
AB  - Sulphonylureas (SUs) used in the treatment for type 2 diabetes have been shown to
      result in different clinical outcome. This study hypothesized that three widely
      used SUs, glibenclamide, glimepiride and gliclazide, may affect function and
      survival of insulin-producing cells differently. To evaluate differences between
      SUs, insulin secretion and cell death were measured, and genome-wide gene
      expression patterns were compared using a bioinformatics approach focusing on
      functional relationships between molecules. Insulin-producing INS-1E cells
      exposed to SUs for 6 and 24 hr were assayed using GeneChip. Cluster and pathway
      analyses were used to identify differentially expressed genes and patterns of
      potential biological functions associated with SU treatment. Cell death was
      measured using acridine orange/Hoechst 33342 staining. Short-term treatment (6
      hr) yielded up-regulation of insulin secretion and genes associated with insulin
      secretion for all three SUs applied. While long-term treatment (24-72 hr) with
      gliclazide did not change gene expression or cell survival, treatment with
      glibenclamide or glimepiride up-regulated genes associated with oxidative stress
      and hypoxia, but did not induce cell death. Short-term treatment with SUs
      initiates gene regulation that can be attributed to insulin secretion with few
      differences between individual SUs. This regulation was temporal and returned to
      baseline after 24 hr. Individual differences observed after 24-72 hr indicate
      that glibenclamide and glimepiride induce potentially harmful cell signalling
      insufficient for triggering beta cell death.

PMID- 22642399
TI  - Preliminary studies of chemical immobilization of captive juvenile estuarine
      (Crocodylus porosus) and Australian freshwater (C. johnstoni) crocodiles with
      medetomidine and reversal with atipamezole.
AB  - OBJECTIVE: To establish a safe, reliable and reversible immobilization protocol
      for captive juvenile crocodiles. STUDY DESIGN: Prospective, randomized, clinical
      study. ANIMALS: Thirty male estuarine crocodiles (body mass 1-12.1 kg) and 10
      male Australian freshwater crocodiles (body mass 4.1-12.8 kg). METHODS: An
      optimized dose of medetomidine (0.5 mg kg(-1)) was administered intramuscularly
      (IM) into the tail (Group 1; n = 5), pelvic limb (Group 2; n = 5) and thoracic
      limb (Groups 3 and 4; n = 5 in each group) of estuarine crocodiles weighing 3
      12.1 kg. Their heart and respiratory rates and degree of immobilization were
      monitored every 15 minutes until recovery and daily thereafter for 3 subsequent
      days. In Group 4 (n = 5), medetomidine was antagonized with an optimized dose of
      atipamezole (2.5 mg kg(-1)) given IM into the thoracic limb and time to recovery
      recorded. The effects of increasing doses of medetomidine given IM in the
      thoracic limb (n = 4) and intravenously (n = 6) were determined in 1-2 kg
      estuarine crocodiles. Australian freshwater crocodiles (4.1-12.8 kg) were
      administered medetomidine IM into the thoracic limb in divided doses at 0.5 mg
      kg(-1) (n = 5) and 0.75 mg kg(-1) (n = 5) and similarly monitored. RESULTS:
      Immobilization was achieved only in the estuarine crocodiles >3 kg and when
      medetomidine was administered into the thoracic limb. Immobilization was achieved
      within 30 minutes and the duration of immobilization lasted approximately 90
      minutes. Immobilization in estuarine crocodiles was readily reversed with
      atipamezole. A dose of 0.75 g kg(-1) was required to immobilize Australian
      freshwater crocodiles and the onset of immobilization was longer and the duration
      shorter than seen in the estuarine crocodiles. The heart and respiratory rates of
      all immobilized animals decreased significantly and arterial blood pressure
      became undetectable in the animals in which it was measured. CONCLUSIONS AND
      CLINICAL RELEVANCE: Medetomidine administered in the thoracic limb of captive
      estuarine and Australian freshwater crocodiles, ranging from 3 to 12.8 kg,
      provides a predictable onset and duration of immobilization sufficient for
      physical examination, sample collection, short minor procedures and translocation
      of the animals. Atipamezole administered in the thoracic limb results in complete
      reversal of the effects of medetomidine in the estuarine crocodile and a rapid
      return to normal behaviour.

PMID- 22642401
TI  - Prevalence of smoking and other health risk factors in people attending
      residential substance abuse treatment.
AB  - INTRODUCTION AND AIMS: People attending substance abuse treatment have an
      elevated risk of developing cardiovascular disease (CVD) and cancer.
      Consequently, there have been increasing calls for substance abuse treatment
      services to address smoking. The current study examined smoking behaviours of
      people attending residential substance abuse treatment. Additionally, the study
      examined rates of other potentially modifiable health risk factors for the
      development of CVD and cancer. DESIGN AND METHODS: A cross-sectional survey was
      completed by participants attending Australian Salvation Army residential
      substance abuse treatment services (n = 228). Rates of smoking, exercise, dietary
      fat intake, body mass index and depression were identified and compared with
      representative community populations. The relationship between length of
      treatment and changes in these variables was also examined. RESULTS: When
      compared with the Australian population, participants were much more likely to be
      current smokers. They also showed higher rates of dietary fat intake, and having
      had a previous diagnosis of a depressive disorder. Encouragingly, participants
      were more likely to be engaging in regular exercise. Over a third of all smokers
      reported having increased their smoking since attending the residential program,
      with correlational analysis suggesting that nicotine dependence was increasing
      the longer participants were in treatment. DISCUSSION AND CONCLUSIONS: People
      attending substance abuse treatment show extremely high rates of smoking (77%).
      With the large majority of participants showing multiple risk factors for CVD, it
      is important that residential services consider strategies to address smoking and
      the other potentially modifiable health risk factors in an integrated fashion.

PMID- 22642400
TI  - Culture but not gender modulates amygdala activation during explicit emotion
      recognition.
AB  - BACKGROUND: Mounting evidence indicates that humans have significant difficulties
      in understanding emotional expressions from individuals of different ethnic
      backgrounds, leading to reduced recognition accuracy and stronger amygdala
      activation. However, the impact of gender on the behavioral and neural reactions
      during the initial phase of cultural assimilation has not been addressed.
      Therefore, we investigated 24 Asians students (12 females) and 24 age-matched
      European students (12 females) during an explicit emotion recognition task, using
      Caucasian facial expressions only, on a high-field MRI scanner. RESULTS: Analysis
      of functional data revealed bilateral amygdala activation to emotional
      expressions in Asian and European subjects. However, in the Asian sample, a
      stronger response of the amygdala emerged and was paralleled by reduced
      recognition accuracy, particularly for angry male faces. Moreover, no significant
      gender difference emerged. We also observed a significant inverse correlation
      between duration of stay and amygdala activation. CONCLUSION: In this study we
      investigated the "alien-effect" as an initial problem during cultural
      assimilation and examined this effect on a behavioral and neural level. This
      study has revealed bilateral amygdala activation to emotional expressions in
      Asian and European females and males. In the Asian sample, a stronger response of
      the amygdala bilaterally was observed and this was paralleled by reduced
      performance, especially for anger and disgust depicted by male expressions.
      However, no gender difference occurred. Taken together, while gender exerts only
      a subtle effect, culture and duration of stay as well as gender of poser are
      shown to be relevant factors for emotion processing, influencing not only
      behavioral but also neural responses in female and male immigrants.

PMID- 22642402
TI  - Markers of coagulation, fibrinolysis and inflammation in relation to post
      thrombotic syndrome.
AB  - BACKGROUND: Post-thrombotic syndrome (PTS) occurs in 20-50% of patients after a
      deep venous thrombosis (DVT). It is difficult to accurately predict which
      patients will develop PTS. Biomarkers could be a valuable tool for PTS risk
      assessment. OBJECTIVES: To investigate whether increased levels of factor
      (F)VIII, C-reactive protein (CRP) or D-dimer, over time, are associated with the
      development of PTS in patients after an acute DVT. METHODS: PTS status was
      assessed using the Villalta scale. Blood sampling was performed at three points
      during follow-up. RESULTS: A cohort of 228 consecutive patients was included
      after an acute DVT. At T1 (12 months after index DVT), both levels of D-dimer
      (median 725 ng mL(-1) [interquartile range, IQR 400-1400[ vs. 378 ng mL(-1) [251
      652] P=0.004) and CRP (median 3.9 mg L(-1) [IQR 1.6-8.5] vs. 2.4 mg L(-1) [1.0
      4.3] P=0.018) were increased in patients with PTS, compared with patients without
      PTS. Factor (F)VIII was not associated with PTS. In the multivariate logistic
      regression analysis, varicosities (odds ratio [OR] 13.4 95% confidence interval
      [CI] 3.0-59.1 P=0.001), a previous ipsilateral DVT (OR 6.3 95% CI 1.5-26.9
      P=0.012) and CRP>5 mg L(-1) on T1 (OR 8.0 95% CI 2.4-26.4 P=0.001) were
      significantly associated with PTS. CONCLUSIONS: Besides previous ipsilateral DVT
      and varicosities, CRP>5 mg L(-1) at T1 was strongly and independently associated
      with PTS. Persistent inflammation rather than hypercoagulability might be the
      most important etiological factor in PTS, and may be a target for future therapy.
      The development of a risk score for PTS, including both clinical risk factors and
      biomarker levels, such as CRP, might be desirable.

PMID- 22642403
TI  - Medium-chain-length polyhydroxyalkanoate production by newly isolated Pseudomonas
      sp. TN301 from a wide range of polyaromatic and monoaromatic hydrocarbons.
AB  - AIMS: The aim of this study was to convert numerous polyaromatic and monoaromatic
      hydrocarbons into biodegradable polymer medium-chain-length polyhydroxyalkanoate
      (mcl-PHA). METHODS AND RESULTS: Using naphthalene enrichment cultivation method,
      we have isolated seven bacterial strains from the river sediment exposed to
      petrochemical industry effluents. In addition to naphthalene, all seven strains
      could utilize between 12 and 17 different aromatic substrates, including toluene,
      benzene and biphenyl. Only one isolate that was identified as Pseudomonas sp.
      TN301 could accumulate mcl-PHA from naphthalene to 23% of cell dry weight. Owing
      to poor solubility, a method of supplying highly hydrophobic polyaromatic
      hydrocarbons to a culture medium was developed. The best biomass and mcl-PHA
      yields were achieved with the addition of synthetic surfactant Tween 80 (0.5 g l(
      1)). We have shown that Pseudomonas sp. TN301 can accumulate mcl-PHA from a wide
      range of polyaromatic and monoaromatic hydrocarbons, and mixtures thereof, while
      it could also accumulate polyphosphates and was tolerant to the presence of heavy
      metal (100 mmol l(-1) cadmium and 20 mmol l(-1) nickel). CONCLUSIONS: A new
      Pseudomonas strain was isolated and identified with the ability to accumulate mcl
      PHA from a variety of aromatic hydrocarbons. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study is the first report on the ability of a bacterial strain to
      convert a range of polyaromatic hydrocarbon compounds to the biodegradable
      polymer (mcl-PHA). Mcl-PHA is gaining importance as a promising biodegradable
      thermoelastomer, and therefore, isolation of new producing strains is highly
      significant. Furthermore, this strain has the ability to utilize a range of
      hydrocarbons, which often occur as mixtures and could potentially be employed in
      the recently described efforts to convert waste materials to PHA.

PMID- 22642404
TI  - The prevalence, treatment and outcomes of agitation among patients with brain
      injury admitted to acute care units.
AB  - PURPOSE: Agitation occurs in 70% of patients hospitalized with traumatic brain
      injury (TBI) and has adverse effects on length of stay and functional outcomes.
      Treatment involves pharmacological and behavioural interventions. Much research
      on TBI agitation has been conducted in intensive care or rehabilitation settings.
      This study aimed to identify agitation prevalence, treatment and outcomes among
      patients with TBI on acute care wards. METHODS: Data abstracted from the trauma
      registry and medical records of adult patients with TBI admitted to an acute care
      ward within a Level I trauma centre over 12 months. FINDINGS: From 219 patients,
      at least one agitation behaviour was present in 41% (n = 90) of patients.
      Clinically significant agitation was present in 8% (n = 18) of patients.
      Agitation behaviours included impulsiveness (30%), pulling at devices (21%) and
      decreased attention span (16%). Common interventions were reorientation (33%),
      constant supervision (32%) and benzodiazepines (30%). Agitated patients had
      longer length of stay (p < 0.001) and were less likely to be discharged home.
      Physical restraints, constant supervision, redirection, reorientation and
      environmental modifications were associated with agitation (p < 0.001).
      IMPLICATIONS: Management of agitation among patients with TBI on acute care wards
      can present challenges to healthcare staff. Innovative approaches are needed to
      promote outcomes using available resources.

PMID- 22642405
TI  - Endogenous oestradiol as a positive correlate of plasma fibrinogen among older
      postmenopausal women: a population-based study (the Three-City cohort study).
AB  - BACKGROUND: Plasma fibrinogen is a strong predictor of ischaemic arterial disease
      in women. Sex steroid hormones including hormone therapy may play an important
      role in the development of cardiovascular disease. However, whether endogenous
      sex steroid hormones influence the plasma fibrinogen concentrations among
      postmenopausal women remains unclear. OBJECTIVES: To investigate the association
      of plasma fibrinogen levels with endogenous sex steroid hormones and sex hormone
      binding globulin (SHBG) among postmenopausal women. METHODS: We used data from
      the French prospective Three-City cohort study that included 9294
      noninstitutionalized men and women over 65 years of age. Total 17beta-oestradiol
      (E2, pg/ml), total testosterone (T, ng/ml), SHBG (nm) and fibrinogen (g/l) were
      measured in stored plasmas in a subcohort of 602 randomly selected postmenopausal
      women who used neither hormone medication nor anticoagulation therapy.
      Multivariate linear regression models were used to estimate the regression
      coefficients assessed in fibrinogen unit by 1 SD increase in log-distribution of
      sex steroid hormones and SHBG. RESULTS: E2 but neither T nor SHBG was positively
      associated with plasma fibrinogen levels (beta = 0.148, P < 0.001). Adjustment
      for cardiovascular risk factors including diabetes made no substantial change to
      the results (beta = 0.145, P < 0.001). The association of fibrinogen with E2 was
      stronger among women with body mass index over 25 kg/m(2) compared with those
      with normal weight (beta = 0.156, P < 0.001 and beta = 0.092, P = 0.02,
      respectively, P for interaction = 0.04). CONCLUSION: E2 emerges as a positive and
      independent correlate of plasma fibrinogen among postmenopausal women, especially
      in subjects who are overweight. These findings suggest a deleterious effect of
      endogenous oestrogens on cardiovascular risk profile among postmenopausal women.

PMID- 22642406
TI  - Occupational-level interactions between physical hazards and cognitive ability
      and skill requirements in predicting injury incidence rates.
AB  - Interactions between occupational-level physical hazards and cognitive ability
      and skill requirements were examined as predictors of injury incidence rates as
      reported by the U. S. Bureau of Labor Statistics. Based on ratings provided in
      the Occupational Information Network (O*NET) database, results across 563
      occupations indicate that physical hazards at the occupational level were
      strongly related to injury incidence rates. Also, as expected, the physical
      hazard-injury rate relationship was stronger among occupations with high
      cognitive ability and skill requirements. In addition, there was an unexpected
      main effect such that occupations with high cognitive ability and skill
      requirements had lower injury rates even after controlling for physical hazards.
      The main effect of cognitive ability and skill requirements, combined with the
      interaction with physical hazards, resulted in unexpectedly high injury rates for
      low-ability and low-skill occupations with low physical hazard levels.
      Substantive and methodological explanations for these interactions and their
      theoretical and practical implications are offered. Results suggest that
      organizations and occupational health and safety researchers and practitioners
      should consider the occupational level of analysis and interactions between
      physical hazards and cognitive requirements in future research and practice when
      attempting to understand and prevent injuries.

PMID- 22642407
TI  - Linking perceptions of role stress and incivility to workplace aggression: the
      moderating role of personality.
AB  - Although research on workplace aggression has long recognized job stressors as
      antecedents, little is known about the process through which employee responses
      to stressful workplace demands escalate from relatively mild interactions into
      more intense behaviors. This study investigates the influence that employees'
      perceptions of role stress (ambiguity, conflict, overload) have on their
      aggressive behavior by affecting their perceptions of incivility, and whether
      these downstream effects depend on personality traits (neuroticism,
      agreeableness, conscientiousness). Results supported moderated mediation, such
      that the indirect effects of perceived role ambiguity and role conflict on
      enacted aggression through experienced incivility varied according to individual
      differences in personality.

PMID- 22642409
TI  - An empirical test of forgiveness motives' effects on employees' health and well
      being.
AB  - Two critical-incident studies were conducted to determine what motivates
      employees to forgive (or reconcile) with coworkers who offend them. Data from the
      first study's exploratory factor analysis revealed five types of motives for
      forgiveness: apology, moral, religious, relationship, and lack of alternatives.
      Data from the second study on a different sample confirmed the five-factor
      structure, and structural equation modeling demonstrated differential
      relationships between the five motives and the outcome variables, stress and
      health. Individuals who claimed to have forgiven because they believed they had
      no other alternatives, or who forgave because they believed a higher power
      (religious) required it, were more likely to report greater stress and poorer
      health. Positive outcomes of forgiveness were discovered for those employees who
      forgave because they believed it was the right (moral) thing to do. Those who
      forgave for moral reasons reported less stress than those who forgave because
      they believed they had no other choice or because a higher power demanded it.
      Forgiving for relationship and apology reasons was not significantly related to
      either stress or general health. Future research directions are discussed.

PMID- 22642408
TI  - Developmental trajectories of work-family conflict for Finnish workers in
      midlife.
AB  - This study investigated the developmental trajectories of work-family conflict
      among the same participants (n = 277; 48% female) at ages 36, 42, and 50. Across
      this 14-year time span, with respect to the sample as a whole, there was no
      significant change in the mean levels of work-to-family conflict (WFC) or family
      to-work conflict (FWC). However, latent profile analyses revealed four latent
      trajectories within the sample, showing both mean-level stability and change in
      WFC and FWC: (1) "WFC decreasing" (n = 151); (2) "WFC and FWC stable low" (n =
      105); (3) "WFC and FWC increasing" (n = 14); and (4) "FWC decreasing" (n = 7). Of
      these trajectories the strongest contrast existed between the WFC and FWC stable
      low and the WFC and FWC increasing trajectories: the former had the lowest and
      the latter the highest number of weekly working hours at ages 36, 42, and 50, and
      in the former but not in the latter the number of children living at home
      significantly decreased from age 36 to 50. Also, at ages 42 and 50 the WFC and
      FWC increasing trajectory showed higher job exhaustion and depressive symptoms
      than the WFC and FWC stable low trajectory. Altogether these findings suggest
      that work-family conflict is not limited to the early part of employees' working
      career and that developmental trajectories of work-family conflict exhibit a
      substantial amount of heterogeneity.

PMID- 22642410
TI  - Preparation of an amide group-connected graphene-polyaniline nanofiber hybrid and
      its application in supercapacitors.
AB  - Polyaniline (PANI) nanofiber is grafted onto graphene to obtain a novel graphene
      polyaniline (GP) hybrid. Graphene is activated using SOCl2 and reacts with PANI
      to form an amide group that intimately connects graphene and PANI. The existence
      of the amide group and its anchoring effect in the GP hybrid are confirmed and
      characterized by SEM, TEM, FT-IR, Raman, XPS and quantum chemistry analyses.
      Electrochemical tests reveal that the GP hybrid has high capacitance performances
      of 579.8 and 361.9 F g(-1) at current densities of 0.3 and 1 A g(-1). These
      values indicate superiority to materials interacted by van der Waals force. Long
      term charge/discharge tests at high current densities show that the GP hybrid
      preserves 96% of its initial capacitance, demonstrating good electrochemical
      stability. The improved electrochemical performance suggests promising
      application of the GP hybrid in high-performance supercapacitors. 

PMID- 22642412
TI  - What event-related potentials (ERPs) bring to social neuroscience?
AB  - Social cognitive neuroscience is a recent interdisciplinary field that studies
      the neural basis of the social mind. Event-related potentials (ERPs) provide
      precise information about the time dynamics of the brain. In this study, we
      assess the role of ERPs in cognitive neuroscience, particularly in the emerging
      area of social neuroscience. First, we briefly introduce the technique of ERPs.
      Subsequently, we describe several ERP components (P1, N1, N170, vertex positive
      potential, early posterior negativity, N2, P2, P3, N400, N400-like, late positive
      complex, late positive potential, P600, error-related negativity, feedback error
      related negativity, contingent negative variation, readiness potential,
      lateralized readiness potential, motor potential, re-afferent potential) that
      assess perceptual, cognitive, and motor processing. Then, we introduce ERP
      studies in social neuroscience on contextual effects on speech, emotional
      processing, empathy, and decision making. We provide an outline of ERPs'
      relevance and applications in the field of social cognitive neuroscience. We also
      introduce important methodological issues that extend classical ERP research,
      such as intracranial recordings (iERP) and source location in dense arrays and
      simultaneous functional magnetic resonance imaging recordings. Further, this
      review discusses possible caveats of the ERP question assessment on
      neuroanatomical areas, biophysical origin, and methodological problems, and their
      relevance to explanatory pluralism and multilevel, contextual, and situated
      approaches to social neuroscience.

PMID- 22642411
TI  - Novel models for bacterial colonization and infection of full-thickness wounds in
      rats.
AB  - An animal model is needed to study the pathophysiology of wound infections;
      however, an animal model that is reproducible and clinically relevant has not
      previously been available. In addition, an animal model of wound colonization
      generated in a manner similar to the wound infection model would be useful. Here,
      we describe new animal models of the wound infection continuum for the
      characterization of essential host-pathogen relationships. We determined the
      conditions needed to establish rat models of stable wound colonization and
      infection, without the use of disturbing factors (e.g., foreign bodies or
      induction of diabetes mellitus). We found that the age of the rats, bacterial
      inoculum size, and wound location were important elements in generating
      reproducible, obvious, spreading wound infections. We inoculated approximately 6
      month-old rats with 2.06 * 10(9) or 4.12 * 10(9) colony-forming units of
      Pseudomonas aeruginosa to generate the wound colonization and wound infection
      models, respectively. Wounds were made 2 cm cranial to the greater trochanter.
      These clinically relevant and highly reproducible animal models can be used to
      investigate the mechanisms of wound infection and monitor the effect of
      therapeutic agents in vivo.

PMID- 22642413
TI  - Effect of intraperitoneal or incisional bupivacaine on pain and the analgesic
      requirement after ovariohysterectomy in dogs.
AB  - OBJECTIVE: To compare the effect of intraperitoneal (IP) or incisional (INC)
      bupivacaine on pain and the analgesic requirement after ovariohysterectomy in
      dogs. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Thirty
      female dogs undergoing ovariohysterectomy (OHE). METHODS: Dogs admitted for
      elective OHE were anesthetized with acepromazine, butorphanol, thiopental and
      halothane. Animals were randomly assigned to one of three groups (n = 10 per
      group). The treatments consisted of preincisional infiltration with saline
      solution (NaCl 0.9%) or bupivacaine with epinephrine and/or IP administration of
      the same solutions, as follows: INC and IP 0.9% NaCl (control group); INC 0.9%
      NaCl and IP bupivacaine (5 mg kg(-1), IP group); INC bupivacaine (1 mg kg(-1))
      and IP 0.9% NaCl (INC group). Postoperative pain was evaluated by a blinded
      observer for 24 hours after extubation by means of a visual analog scale (VAS)
      and a numeric rating scale (NRS). Rescue analgesia (morphine, 0.5 mg kg(-1) , IM)
      was administered if the VAS was >5/10 or the NRS >10/29. RESULTS: At 1 hour after
      anesthesia, VAS pain scores were [medians (interquartile range)]: 6.4 (3.1-7.9),
      0.3 (0.0-2.6) and 0.0 (0.0-7.0) in control, IP and INC groups, respectively. VAS
      pain scores were lower in the IP compared to the control group. Over the first 24
      hours, rescue analgesia was administered to 7/10, 5/10 and 3/10 dogs of the
      control, INC and IP groups, respectively. Total number of dogs given rescue
      analgesia over the first 24 hours did not differ significantly among groups.
      CONCLUSIONS AND CLINICAL RELEVANCE: Intraperitoneal bupivacaine resulted in lower
      pain scores during the first hour of the postoperative period and there was a
      trend towards a decreased need for rescue analgesia after OHE in dogs.

PMID- 22642414
TI  - Treatment outcomes for methamphetamine users receiving outpatient counselling
      from the Stimulant Treatment Program in Australia.
AB  - INTRODUCTION AND AIMS: The purpose of this study was to document treatment
      outcomes for methamphetamine users receiving outpatient counselling from the
      Stimulant Treatment Program (STP) in Australia. DESIGN AND METHODS: Clients
      attending the STP for methamphetamine use (n = 105) were assessed on entry to the
      service and at 3 (n = 86) and 6 months (n = 83) after starting treatment. At each
      interview methamphetamine use (days of use, severity of dependence), other drug
      use and health and social functioning (HIV risk behaviour, crime, disability,
      psychotic symptoms and hostility) were assessed for the past month. RESULTS:
      Participants received a median of six counselling sessions (interquartile range 1
      11) over a period of 89 days (interquartile range 41-148 days). Past month
      methamphetamine use fell from 79% at treatment entry to 53% at the 3-month follow
      up (P < 0.001) and 55% at the 6-month follow-up (P < 0.001). There were
      statistically significant reductions in psychotic symptoms, hostility and
      disability associated with poor mental health. There was no change in other drug
      use, crime or HIV risk behaviour. Reductions in methamphetamine were more common
      among younger participants, those who had no history of drug treatment and those
      without concurrent heroin use. DISCUSSION AND CONCLUSIONS: Methamphetamine users
      entering the STP showed reductions in methamphetamine use and improvements in
      their mental health after treatment. Improved treatment responses are needed to
      address polydrug use and other harms within in this population.

PMID- 22642415
TI  - Dorsal penile nerve block prior to inflatable penile prosthesis placement: a
      randomized, placebo-controlled trial.
AB  - INTRODUCTION: Dorsal penile nerve block (DPNB) has been previously shown to
      provide effective analgesia for penile surgeries. To date, few studies have
      examined the role of DPNB prior to inflatable penile prosthesis (IPP)
      implantation. AIM: The purpose of this study was to assess the efficacy of local
      penile nerve block prior to IPP implantation for postoperative pain control. MAIN
      OUTCOME MEASURES: The primary outcome was postoperative pain rated using the
      visual analog scale (VAS). Secondary outcome measures included total narcotic
      usage during hospitalization. METHODS: Institutional Review Board approval was
      obtained. Patients with erectile dysfunction scheduled for IPP implantation were
      approached for study participation. Patients were excluded if they had a previous
      IPP scheduled for revision or replacement or were undergoing additional
      procedures during the same operative session. Patients were then randomized to
      either DPNB with 1% lidocaine and 0.5% bupivacaine without epinephrine or
      injectable saline placebo. Only the resident surgeon assisting in the case was
      aware of randomization. All procedures were performed by a single surgeon
      (C.C.C.). Postoperatively, patients were asked to rate their pain using a VAS
      hourly while in recovery, at 4 hours, and at 23 hours postoperatively. Total
      narcotic usage was also measured. RESULTS: A total of 30 patients underwent
      randomization with 15 patients in each group. Baseline demographic data were
      similar in each group. There was a significant reduction in pain in the immediate
      postoperative period and at 4 hours after surgery in the treatment group when
      compared with placebo (VAS 2.5 vs. 5.3, P = 0.009 at 0 hours; VAS 2.8 vs. 5.1, P
      = 0.011 at 4 hours). Narcotic usage was similar among both groups. There were no
      perioperative or early postoperative complications in either group. CONCLUSIONS:
      DPNB is safe and effective for reducing pain in the early postoperative period
      following penile prosthesis implantation.

PMID- 22642416
TI  - Long-acting kappa opioid antagonists nor-BNI, GNTI and JDTic: pharmacokinetics in
      mice and lipophilicity.
AB  - BACKGROUND: Nor-BNI, GNTI and JDTic induce kappa opioid antagonism that is
      delayed by hours and can persist for months. Other effects are transient. It has
      been proposed that these drugs may be slowly absorbed or distributed, and may
      dissolve in cell membranes, thus slowing elimination and prolonging their
      effects. Recent evidence suggests, instead, that they induce prolonged
      desensitization of the kappa opioid receptor. METHODS: To evaluate these
      hypotheses, we measured relevant physicochemical properties of nor-BNI, GNTI and
      JDTic, and the timecourse of brain and plasma concentrations in mice after
      intraperitoneal administration (using LC-MS-MS). RESULTS: In each case, plasma
      levels were maximal within 30 min and declined by >80% within four hours,
      correlating well with previously reported transient effects. A strong negative
      correlation was observed between plasma levels and the delayed, prolonged
      timecourse of kappa antagonism. Brain levels of nor-BNI and JDTic peaked within
      30 min, but while nor-BNI was largely eliminated within hours, JDTic declined
      gradually over a week. Brain uptake of GNTI was too low to measure accurately,
      and higher doses proved lethal. None of the drugs were highly lipophilic, showing
      high water solubility (> 45 mM) and low distribution into octanol (log D7.4 < 2).
      Brain homogenate binding was within the range of many shorter-acting drugs (>7%
      unbound). JDTic showed P-gp-mediated efflux; nor- BNI and GNTI did not, but their
      low unbound brain uptake suggests efflux by another mechanism. CONCLUSIONS: The
      negative plasma concentration-effect relationship we observed is difficult to
      reconcile with simple competitive antagonism, but is consistent with
      desensitization. The very slow elimination of JDTic from brain is surprising
      given that it undergoes active efflux, has modest affinity for homogenate, and
      has a shorter duration of action than nor-BNI under these conditions. We propose
      that this persistence may result from entrapment in cellular compartments such as
      lysosomes.

PMID- 22642418
TI  - The expression of PGC-1alpha in the mice brain after traumatic brain injury.
AB  - BACKGROUND: Peroxisome proliferator activated receptor gamma co-activator-1alpha
      (PGC-1alpha) is a transcriptional co-activator that co-ordinately regulates genes
      required for mitochondrial biogenesis and is a key contributor to the up
      regulation of antioxidant activities in response to oxidative stress. The
      expression pattern of PGC-1alpha after traumatic brain injury (TBI) has not been
      studied. MATERIALS AND METHODS: Ninety male ICR mice (28-32 g) were randomly
      assigned to six groups: sham, 3, 6, 12, 24 and 48 hours after TBI. PGC-1alpha
      mRNA levels in mice brain were detected by reverse-transcriptase polymerase chain
      reaction and its nuclear protein levels by Western blot from 3-48 hours after
      TBI. PGC-1alpha distribution in the cerebral cortex after TBI was investigated by
      immunohistochemistry. MAIN OUTCOMES AND RESULTS: The PGC-1alpha mRNA level
      significantly increased from 3 hours after TBI, peaked at 6 hours and gradually
      decreased from 12 to 48 hours. The nuclear PGC-1alpha protein level increased
      from 6 to 24 hours after TBI and decreased at 48 hours after TBI. Increased PGC
      1alpha immunostaining was detected in the neurons of the cerebral cortex at 12
      hours after TBI. CONCLUSION: PGC-1alpha may play an important role in the brain
      after TBI.

PMID- 22642417
TI  - Is there value in kinetic modeling of thrombin generation? Yes.

PMID- 22642420
TI  - Future of low specific activity molybdenum-99/technetium-99m generator.
AB  - In last few years, the shortage of molybdenum-99 (99Mo) was felt in the developed
      and developing countries hospitals, where diagnostic nuclear medicine is
      practiced. To overcome the shortage of 99Mo various routes of its production by
      accelerators and reactors generating low and high specific activity products have
      been planned. High specific activity 99Mo obtained by fission of uranium-235
      (235U) has completely dominated in the manufacturing of technetium-99m (99mTc)
      generators in last 3-4 decades, but due to proliferation and dirty bomb, issues
      non fission routes of 99Mo production are emphasized. Future of low specific
      activity 99Mo is discussed.

PMID- 22642419
TI  - Are obstetrical, perinatal, and infantile difficulties associated with pediatric
      bipolar disorder?
AB  - OBJECTIVES: Despite increasing acknowledgement of bipolar disorder (BD) in
      childhood, there is a paucity of literature that has investigated obstetrical,
      perinatal, and infantile difficulties and their potential link with BD. To this
      end, we examined difficulties during delivery, immediate post-birth, and infancy
      and the association with BD in childhood. METHODS: From two similarly designed,
      ongoing, longitudinal, case-control family studies of pediatric BD (N = 327
      families), we analyzed 338 children and adolescents [mean (+/- standard
      deviation) age: 12.00 +/- 3.37 years]. We stratified them into three groups:
      healthy controls (N = 98), BD probands (N = 120), and their non-affected siblings
      (N = 120). All families were comprehensively assessed with a structured
      psychiatric diagnostic interview for psychopathology and substance use. Mothers
      were directly questioned regarding the pregnancy, delivery, and infancy
      difficulties that occurred with each child using a module from the Diagnostic
      Interview for Children and Adolescents-Parent Version (DICA-P). RESULTS: Mothers
      of BD subjects were more likely to report difficulties during infancy than
      mothers of controls [odds ratio (95% confidence interval) = 6.6 (3.0, 14.6)].
      Specifically, children with BD were more likely to have been reported as a
      stiffened infant [7.2 (1.1, 47.1)] and more likely to have experienced 'other'
      infantile difficulties [including acting colicky; 4.9 (1.3, 18.8)] compared to
      controls. We found no significant differences between groups in regards to
      obstetrical or perinatal difficulties (all p values > 0.05). CONCLUSIONS: While
      our results add to previous literature on obstetrical and perinatal difficulties
      and BD, they also highlight characteristics in infancy that may be prognostic
      indicators for pediatric BD.

PMID- 22642421
TI  - Synthesis of [DTPA-bis(D-ser)] chelate (DBDSC): an approach for the design of
      SPECT radiopharmaceuticals based on technetium.
AB  - D-Serine is a physiological coagonist of the N-methyl D-aspartate (NMDA) type of
      glutamate receptor-a key excitatory neurotransmitter receptor in the brain. D
      Serine appears to be a part of the synapse through a variety of transporters
      located on both neurons and astrocytes. The development of 99mTc radiolabeled
      amino acid based radiopharmaceuticals for imaging a variety of tumors has found
      to be useful in diagnostic imaging. Diethylene triamine penta acetic acid (DTPA)
      is one of the most well-known chelating reagent for the production of stable
      complexes with various heavy metal ions. We have synthesized [DTPA-bis(D-ser)] in
      90% yield and analyzed the chelate by spectroscopic techniques. The DBDSC chelate
      binds to 99mTc with high efficiency at ambient temperature. The resulting chelate
      is stable under physiological conditions (37oC, pH=7.4) for at least 24 h after
      radiocomplexation. The receptor binding studies of 99mTc-[DTPA-bis(D-ser)] in
      established lung adeno carcinoma A549 exhibited Kd value to be 26nM. A549 Tumor
      in athymic mice was accumulated in the gamma-images. The major accumulation of
      the radiotracer was observed in tumor, followed by kidneys. 99mTc-[DTPA-bis(D
      ser)] has promising utility as SPECT-radiopharmaceutical.

PMID- 22642422
TI  - Editorial: The role of nuclear medicine in the management of patients with
      glioblastoma multiforme.

PMID- 22642423
TI  - The emerging role of stereotactic radiosurgery in the treatment of glioblastoma
      multiforme.
AB  - Stereotactic radiosurgery is an emerging treatment option offered to patients
      with Glioblastoma multiforme (GBM). Radiosurgery is performed as an outpatient
      procedure and provides a safe and effective non invasive treatment for focal GBM.
      High energy beams originating from cobalt sources placed into an helmet (Gamma
      Knife) or generated by a linear accelerator (LINAC) rotating on a gantry (X
      Knife, Novalis) or maneuvered by a robotic arm (CyberKnife) are delivered with
      submillimetric accuracy to a selected intracranial target. Treatment accuracy is
      provided by image-guided volumetric CT and MR studies complemented with advanced
      metabolic neuroimaging techniques such as CT-PET. Radiosurgery is typically used
      as a salvage treatment in patients with recurrent GBM to avoid further surgical
      procedures or as a complement to conventional fractionated radiotherapy. This
      paper reviews the emerging role of stereotactic radiosurgery in the treatment of
      GBM.

PMID- 22642424
TI  - Advanced neuroimaging techniques in the management of glioblastoma multiforme.
AB  - Despite the extensive research efforts over the past century, glioblastoma
      multiforme (GBM) remains an ominous diagnosis leading fast to progressive
      disability and death despite the aggressive treatment including microsurgical
      resection, chemotherapy, radiotherapy and stereotactic radiosurgery. Advanced
      neuroimaging techniques, such as volumetric acquisitions, spectroscopy, diffusion
      and perfusion studies added to conventional imaging, provide in selected cases a
      non-invasive alternative to pathological diagnosis but they are also precious
      tools to define the boundaries of image-guided microsurgical resection and/or
      radiosurgical ablation. This paper reviews the role of advanced neuroimaging
      techniques in the diagnosis and treatment of GBM.

PMID- 22642425
TI  - Glioblastoma multiforme imaging: the role of nuclear medicine.
AB  - Glioblastoma multiforme (GBM) is the most common and most malignant primary brain
      tumor occurring during adulthood. The incidence of GBM is nearly 5 cases per
      100,000 population per year. The standard of care for newly diagnosed GBM
      includes surgical resection when possible, followed by radiotherapy and
      concomitant and adjuvant chemotherapy with temozolomide. Imaging modalities used
      in nuclear medicine, namely positron emission tomography (PET) and single-photon
      emission computed tomography (SPECT) have been employed towards the evaluation of
      brain tumors. Herewith, we discuss the value of the above imaging techniques in
      the assessment of GBM aggressiveness, in the distinction of treatment induced
      necrosis from glioma recurrence, in the estimation of overall prognosis and in
      the evaluation of treatment response in patients with GBM.

PMID- 22642426
TI  - Electrodialytic ion isolation for matrix removal.
AB  - We report a fully automated online sample pretreatment system for ionic analytes
      that extracts the ionic analytes from the sample and largely removes the nonionic
      sample matrix and can preconcentrate the analyte. Sample pretreatment is a key
      analytical process; conventional pretreatment is conducted in a difficult to
      automate batchwise manner. The present system relies on the transport of ions
      induced by an electric field to a water acceptor. Cations and anions are
      simultaneously and separately collected into individual acceptor streams which
      can be directly introduced to a chemical analyzer. Common inorganic ions (<=10
      meq/L) are quantitatively transferred from samples within a few seconds. Small
      nonionic molecules are transferred by 0.5-10%, and proteins are not transferred
      at all. The method has been successfully applied to drinking water, urine, and
      cow's milk with 3.7 +/- 2.5, 3.8 +/- 2.6, and 4.6 +/- 2.6%, respectively, in
      variance (n = 10). Present results agreed well with those from conventional
      pretreatment methods. Interestingly, when calcium in milk is measured by the
      present method, the results correspond to the total calcium by conventional
      methods; i.e., it can extract calcium from its protein-bound form in milk.

PMID- 22642428
TI  - "Science calls her HeLa".

PMID- 22642427
TI  - Immunofluorescence microscopy to assess enzymes controlling nitric oxide
      availability and microvascular blood flow in muscle.
AB  - OBJECTIVE: The net production of NO by the muscle microvascular endothelium is a
      key regulator of muscle microvascular blood flow. Here, we describe the
      development of a method to quantify the protein content and phosphorylation of
      endothelial NO synthase (eNOS content and eNOS ser(1177) phosphorylation) and
      NAD(P)H oxidase expression. METHODS: Human muscle cryosections were stained using
      antibodies targeting eNOS, p-eNOS ser(1177) and NOX2 in combination with markers
      of the endothelium and the sarcolemma. Quantitation was achieved by analyzing
      fluorescence intensity within the area stained positive for the microvascular
      endothelium. Analysis was performed in duplicate and repeated five times to
      investigate CV. In addition, eight healthy males (age 21 +/- 1 year, BMI 24.4 +/-
      1.0 kg/m(2)) completed one hour of cycling exercise at ~65%VO(2max) . Muscle
      biopsies were taken from the m. vastus lateralis before and immediately after
      exercise and analyzed using the new methods. RESULTS: The CV of all methods was
      between 6.5 and 9.5%. Acute exercise increased eNOS serine(1177) phosphorylation
      (fold change 1.29 +/- 0.05, p < 0.05). CONCLUSIONS: These novel methodologies
      will allow direct investigations of the molecular mechanisms underpinning the
      microvascular responses to insulin and exercise, the impairments that occur in
      sedentary, obese and elderly individuals and the effect of lifestyle
      interventions.

PMID- 22642432
TI  - Considering DSM-5: personality diagnostics in patients with schizophrenia
      spectrum disorders.
AB  - The aims of this study were to examine the prevalence of personality disorders
      (PD) in patients with schizophrenia spectrum disorders (SSD), to examine the
      interaction of axis-I and axis-II symptoms to provide an estimate on the
      confounding potential of SSD psychopathology in the establishment of DSM-IV PD
      diagnoses, and to discuss implications concerning the proposed changes in DSM-5.
      Patients with SSD, aged 18 to 65 years, and being at least partially remitted
      (PANSS total score < 75) were included. PD was examined categorically and
      dimensionally using the SCID-II screening questionnaire and interview, and SSD
      psychopathology was rated using the Positive and Negative Syndrome Scale for
      Schizophrenia (PANSS). Forty-five patients (31 with schizophrenia) were included
      in the current study. Mean age was 37.2 years, and the median duration of illness
      was 9.5 years. Mean PANSS total score was 42.5. The cumulative prevalence of PD
      in our collective was 20%, with obsessive-compulsive, antisocial, and borderline
      PD being the most frequent. There were no cases of cluster A PD diagnoses. In the
      dimensional analysis, numerous correlations of small to medium effect size
      emerged between maladaptive personality traits and SSD psychopathology. PD is
      present in a clinically relevant subgroup of SSD patients and has to be
      recognized in SSD treatment. Currently, it remains unclear to what extent
      correlations between personality traits and SSD symptoms can be explained by
      content overlap or co-variation of SSD psychopathology and PD traits. SSD
      psychopathology may bias PD diagnostics and lead to a higher percentage of
      categorical PD diagnoses, especially considering the proposed changes in DSM-5.

PMID- 22642433
TI  - The role of coping, resilience, and social support in mediating the relation
      between PTSD and social functioning in veterans returning from Iraq and
      Afghanistan.
AB  - Posttraumatic stress disorder (PTSD) is one of the most common psychiatric
      disorders among veterans returning from Iraq and Afghanistan. Little research has
      examined variables that may mediate the relation between PTSD and aspects of
      social functioning, such as relationship satisfaction and family functioning. In
      this cross-sectional study, a total of 164 veterans who were seeking VA primary
      care or mental health care within one year after returning from Iraq and/or
      Afghanistan were screened for PTSD and completed a series of questionnaires that
      assessed social functioning, coping, and life satisfaction. Results showed that
      the 86 (52%) veterans who screened positive for PTSD reported greater
      difficulties in their relationships with romantic partners, less cohesion in
      their families, less social support, poorer social functioning, and lower life
      satisfaction compared to other treatment-seeking veterans. Less social support
      from the community, excessive worry, decreased acceptance of change, and lower
      availability of secure relationships mediated the association between PTSD and
      poor social functioning. The relation between PTSD and lower partner satisfaction
      was mediated by greater cognitive social avoidance and lower availability of
      secure relationships. These results suggest that psychotherapeutic interventions
      that address these mediating variables may help improve social functioning in
      treatment-seeking veterans with PTSD.

PMID- 22642434
TI  - Explanations of firesetting in mentally disordered offenders: a review of the
      literature.
AB  - This paper reviews current explanations of firesetting in adult mentally
      disordered offenders. In particular, attention is given to contemporary research
      that has examined developmental and background characteristics, personality and
      associated traits, motivation for firesetting, neurobiological explanations,
      psychiatric diagnoses, and frequency of self-injurious behavior, including
      suicide. The likelihood of recidivism and associated risk factors is also
      considered. Evaluation of the existing research has highlighted that even though
      a significant proportion has been conducted with psychiatric populations, little
      is understood about firesetting by mentally disordered offenders. In addition,
      little research has been conducted that compares mentally disordered firesetters
      to both other mentally disordered offenders and non-mentally disordered
      offenders. Recommendations are made for future research to further develop
      knowledge of this behavior.

PMID- 22642435
TI  - Depression and sexual satisfaction among female medical students: surprising
      findings from a pilot study.
AB  - We report surprising findings from a pilot study aimed at assessing the
      psychological price paid by female medical students who are also involved in
      serious romantic relationships. Sixty female medical students were assessed as to
      their depressive symptoms, level of self-criticism, sexual satisfaction, role
      commitment, and perceived rewards derived from their professional, marital, and
      domestic roles. The high levels of depressive symptoms found among participants
      in this study were the sole predictor of low sexual satisfaction. Professional
      role reward was positively associated with depressive symptoms. Consistent with
      the notion of multiple roles conflict among self-critical students, role
      commitment and reward in the professional and domestic domains interacted to
      predict depressive symptoms. Results suggest that female medical students
      involved in romantic relationships pay a high emotional price for their
      conflicting role demands.

PMID- 22642436
TI  - Self-other representations mediate the relationship between Five-Factor Model
      depression and depressive states.
AB  - While it is well established that trait depression is a risk factor for
      experiencing increased rates of episodes of depression, it is also the case that
      the ways in which the self and others are perceived, and nature of the
      relationship between self and other, predispose individuals to frequent
      depressive episodes. In this study, 182 psychiatric outpatients at three
      treatment facilities were evaluated for Five-Factor Model depressive traits,
      depressive states, and self-other representations (object relations). It was
      hypothesized that object relations would mediate the relationship between trait
      and state depression. Results partially confirmed this hypothesis. While trait
      depression significantly predicted variance in the Beck Depression Inventory-II
      (BDI-II; Beck et al., 1988), two dimensions of the Bell Object Relations and
      Reality Testing Inventory (BORRTI; Bell, 1995)--Alienation and Insecure
      Attachment--partially mediated the relationship between trait and state
      depression. Similarly, trait depression predicted tendencies to experience
      frequent shifts toward depressive episodes, although the Insecure Attachment and
      Egocentricity scales of the BORRTI fully mediated the relationship between trait
      depression and depressive lability. Knowledge of self-other representations,
      which is being considered for inclusion in the DSM-5, allows for a more refined
      understanding of those factors that contribute shifts in depressive mood.

PMID- 22642437
TI  - Professional competencies for promoting recovery in mental illness.
AB  - This study explored professional caregiving from the perspective of people
      diagnosed with schizophrenia to develop proposed professional competencies for
      promoting recovery. We conducted semi-structured qualitative interviews with 40
      people diagnosed with schizophrenia to explore their experiences of caregiving.
      Interview segments related to professional caregiving were analyzed to derive
      categories and themes that described aspects of caregiving that clients believed
      contributed to their recovery. The proposed competencies derived from the
      interviews overlap with hypothesized competencies identified in the literature,
      but also suggest other areas of skill and attitude that relate to promoting
      recovery, including use of time, talk, and teamwork. The significance
      participants attach to time and talk suggests that services play an important
      role in recovery by creating the space for service users and service providers to
      engage in recovery-promoting practices.

PMID- 22642438
TI  - Anatomical and radiological study of the thoracic paravertebral space in dogs:
      iohexol distribution pattern and use of the nerve stimulator.
AB  - OBJECTIVE: To describe the landmarks and methodology to approach the thoracic
      paravertebral space in dogs; to evaluate if intercostal muscular response could
      be evoked by a nerve-stimulator; to radiographically assess the distribution
      pattern of a radio-opaque contrast medium after thoracic paravertebral
      injections. STUDY DESIGN: Randomized, controlled, experimental trial. ANIMALS:
      Two mongrel dog cadavers (anatomical study) and 24 mongrel dogs (experimental
      study). METHODS: For the anatomic study 0.2 mL kg(-1) of new methylene blue (NMB)
      was injected at the 5th thoracic paravertebral space; for the experimental study
      dogs were divided into three groups and received 1 (T(5)), 2 (T(4) and T(6)) or 4
      (T(4), T(5), T(6) and T(7)) paravertebral injections of iohexol. The
      paravertebral approach was performed with insulated needles using landmarks and a
      blind technique. When the needle tip reached the respective thoracic
      paravertebral space, the nerve-stimulator was switched-on and the
      presence/absence of intercostal muscular twitch was registered, thus a total
      volume of 0.2 mL kg(-1) of iohexol, divided into equal parts for each injection
      point, was administered. Radiological studies were performed with two orthogonal
      projections at different times. Positive injection was confirmed when the
      paravertebral space was occupied by iohexol in both projections. RESULTS: NMB was
      distributed in the T(5) paraverterbal space. In the experimental study, when the
      needle tip reached the respective paravertebral space, intercostal twitching was
      obtained in 80% of the total injections with a stimulating current of 0.5 mA. The
      incidence of positive cases when the intercostal twitch was obtained with 0.5 mA
      was 83.3%. The main distribution pattern observed was cloud like without
      longitudinal diffusion. CONCLUSION AND CLINICAL RELEVANCE: Intercostal muscular
      responses obtained with a stimulating current of 0.5 mA could be useful to locate
      thoracic spinal nerves in dogs and in our study the injected solution was
      confined to one thoracic paravertebral space.

PMID- 22642439
TI  - The orthosteric agonist 2-chloro-5-hydroxyphenylglycine activates mGluR5 and
      mGluR1 with similar efficacy and potency.
AB  - BACKGROUND: The efficacy, potency, and selectivity of the compound 2-Chloro-5
      hydroxyphenylglycine (CHPG), a nominally selective agonist for metabotropic
      glutamate receptor 5 (mGluR5), were examined with select mGluRs by examining
      their ability to induce modulation of the native voltage dependent ion channels
      in isolated sympathetic neurons from the rat superior cervical ganglion (SCG).
      SCG neurons offer a null mGluR-background in which specific mGluR subtypes can be
      made to express via intranuclear cDNA injection. RESULTS: Consistent with
      previous reports, CHPG strongly activated mGluR5b expressed in SCG neurons with
      an apparent EC50 around 60 MUM. Surprisingly, CHPG also activated two mGluR1
      splice variants with a similar potency as at mGluR5 when calcium current
      inhibition was used as an assay for receptor function. No effect of 1 mM CHPG was
      seen in cells expressing mGluR2 or mGluR4, suggesting that CHPG only activates
      group I mGluRs (mGluR1 and 5). CHPG was also able to induce modulation of M-type
      potassium current through mGluR1, but not as consistently as glutamate. Since
      this channel is modulated through a Gq-dependent pathway, these data indicate
      that CHPG may exhibit some biased agonist properties on mGluR1. Closer
      examination of the voltage-independent, Gq-mediated component of mGluR-induced
      calcium current modulation data confirmed that some biased agonism was evident,
      but the effect was weak and inconsistent. CONCLUSIONS: These data contrast with
      the established literature which suggests that CHPG is a selective mGluR5
      agonist. Instead, CHPG appears to act equally well as an agonist at mGluR1. While
      some weak biased agonism was observed with CHPG acting on mGluR1, but not mGluR5,
      favoring Gi/o signaling over Gq/11, this effect does not appear sufficient to
      fully explain the discrepancies in the literature.

PMID- 22642440
TI  - Therapeutic effect of adipose-derived stem cells and BDNF-immobilized PLGA
      membrane in a rat model of cavernous nerve injury.
AB  - INTRODUCTION: Cavernous nerve injury is the main reason for post-prostatectomy
      erectile dysfunction (ED). Stem cell and neuroprotection therapy are promising
      therapeutic strategy for ED. AIM: To evaluate the therapeutic efficacy of adipose
      derived stem cells (ADSCs) and brain-derived neurotrophic factor (BDNF)
      immobilized Poly-Lactic-Co-Glycolic (PLGA) membrane on the cavernous nerve in a
      rat model of post-prostatectomy ED. Methods.  Rats were randomly divided into
      five groups: normal group, bilateral cavernous nerve crush injury (BCNI) group,
      ADSC (BCNI group with ADSCs on cavernous nerve) group, BDNF-membrane (BCNI group
      with BDNF/PLGA membrane on cavernous nerve) group, and ADSC/BDNF-membrane (BCNI
      group with ADSCs covered with BDNF/PLGA membrane on cavernous nerve) group. BDNF
      was controlled-released for a period of 4 weeks in a BDNF/PLGA porous membrane
      system. MAIN OUTCOME MEASURES: Four weeks after the operation, erectile function
      was assessed by detecting the ratio of intra-cavernous pressure (ICP)/mean
      arterial pressure (MAP). Smooth muscle and collagen content were determined by
      Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS) expression in
      the dorsal penile nerve was detected by immunostaining. Phospho-endothelial
      nitric oxide synthase (eNOS) protein expression and cyclic guanosine
      monophosphate (cGMP) level of the corpus cavernosum were quantified by Western
      blotting and cGMP assay, respectively. RESULTS: In the ADSC/BDNF-membrane group,
      erectile function was significantly elevated, compared with the BCNI and other
      treated groups. ADSC/BDNF-membrane treatment significantly increased smooth
      muscle/collagen ratio, nNOS content, phospho-eNOS protein expression, and cGMP
      level, compared with the BCNI and other treated groups. CONCLUSIONS: ADSCs with
      BDNF-membrane on the cavernous nerve can improve erectile function in a rat model
      of post-prostatectomy ED, which may be used as a novel therapy for post
      prostatectomy ED.

PMID- 22642441
TI  - Relationship between perceived and actual frequency represented by common rating
      scale labels.
AB  - Two experiments investigated the relationship between subjective interpretation
      of frequency terms and corresponding objective values. Evidence supported the
      existence of a nonlinear relationship that is well described by a logarithmic
      function. The general form of this relationship was consistent across different
      methods of eliciting subjective frequency estimates and different frequency
      response scales. These findings, in combination with prior research, suggest that
      individuals can be highly accurate in reporting the frequency of prior
      experiences but that subjective reports using common frequency response scales
      and scoring methods should not be taken to reflect equal intervals of actual
      frequency. This bears similarity to psychophysical relationships observed between
      sensation and stimulus intensity, and it has implications for the interpretation
      and analysis of self-report measures that use Likert-type frequency response
      scales.

PMID- 22642442
TI  - The circulating platelet count is not dictated by the liver, but may be
      determined in part by the bone marrow: analyses from human liver and stem cell
      transplantations.
AB  - BACKGROUND: The platelet count varies considerably between individuals, but
      within an individual the platelet count is remarkably stable over time.
      Mechanisms controlling the platelet count are not yet established. OBJECTIVE: In
      the present study, we tested the hypothesis that the liver is important in
      controlling the circulating platelet count, as the liver is the main producer of
      thrombopoietin. METHODS: We compared the platelet count prior to and after liver
      transplantation in >250 patients transplanted for familial amyloidotic
      polyneuropathy (FAP). In contrast to most patients undergoing liver
      transplantation, patients with FAP have normal liver function before
      transplantation. Furthermore, we compared platelet counts in 89 living liver
      donors with the platelet count in the recipients of these grafts. Finally we
      compared platelet counts in donor-recipient pairs of hematopoietic stem cells.
      RESULTS AND CONCLUSIONS: The platelet count prior to transplantation correlated
      with the platelet count at 3 or 12 months after transplantation in patients with
      FAP (r=0.48, P<0.0001 at 3 months, r=0.39, P<0.0001 at 12 months), whereas the
      platelet count in a living liver donor did not correlate with the platelet count
      in the recipient at 3 or 12 months after transplantation (r=0.16, P=0.26 at 3
      months, r=0.11, P=0.30 at 12 months). The platelet count of related donors of
      hematopoietic stem cells correlated with the platelet count in the recipient
      after transplantation (r=0.25, P=0.011). CONCLUSIONS: These results suggest that
      the liver, in spite of being the prime producer of thrombopoietin, does not
      dictate the circulating platelet count, whereas the bone marrow does appear to
      play a role.

PMID- 22642443
TI  - Colloidal stripe pattern with controlled periodicity by convective self-assembly
      with liquid-level manipulation.
AB  - We describe a template-free technique for arranging colloidal particles into a
      stripe pattern on a large scale. A simple liquid-level manipulation system was
      incorporated into the vertical-deposition convective self-assembly (CSA)
      technique. By periodically pumping a colloidal dispersion out of or into a
      reservoir to manipulate the liquid level, we successfully fabricated stripe
      patterns with various periodicities (i.e., line widths and spacings) that are
      unachievable with the normal CSA technique. We developed a simple model to
      predict the periodicity of the resultant colloidal stripes that enables the
      tailored fabrication of colloidal stripes with the desirable periodicity for a
      practical application. This technique has the advantages of versatility and
      scalability. By combining this technique with the two-step CSA technique (Mino et
      al., Langmuir2011, 27(9), 5290-5295), we fabricated a large-sized colloidal grid
      network pattern of silver nanoparticles. 

PMID- 22642444
TI  - Dancing with a ghost revisited.

PMID- 22642446
TI  - Recording sentinel events in the life course of individuals with acquired brain
      injury: a preliminary study.
AB  - OBJECTIVE: To describe the development of the Sentinel Events Questionnaire (SEQ)
      for recording key events occurring during the transition from hospital to home
      following acquired brain injury (ABI) and to examine its participant-proxy
      agreement. DESIGN: Prospective longitudinal design, with the SEQ administered by
      interview prior to discharge and at 1, 3 and 6-months post discharge. MEASURES:
      The SEQ records the occurrence and timing of eight events identified through a
      pilot study and literature review of the transition from hospital to home after
      ABI. SAMPLE: Ninety participants with ABI (64% due to traumatic brain injury and
      26% due to stroke) and their nominated caregivers. RESULTS: All SEQ items had
      high participant-proxy percentage agreement (all >83%). Five items (return to
      work, return to driving, moving to a more restricted living situation, regaining
      independence at home and return to independent use of transport) had good
      agreement based on kappa analyses. The incidence of sentinel events during
      community integration ranged from 18% (relationship breakdown) to 89%
      (independence at home). Participants with TBI were more likely to move to a more
      restrictive living situation and less likely to return to driving than
      participants with stroke (p < 0.05). CONCLUSION: This research highlights the
      benefit of using the SEQ to systematically record the occurrence of sentinel
      events in order to better understand the process of transition from hospital to
      home following ABI.

PMID- 22642447
TI  - Electroanalytical behavior of poly-L-lysine dendrigrafts at the interface between
      two immiscible electrolyte solutions.
AB  - In this work, the electrochemical behavior of nonredox-active poly-L-lysine
      dendrigraft molecules of four different generations was investigated at the
      interface between two immiscible electrolyte solutions (ITIES). The influence of
      the dendrigraft generation on the electrochemical response, sensitivity of the
      calibration curves, and limit of detection was studied. Cyclic voltammetry at the
      ITIES revealed that the sensitivity increased (1840 to 25 800 nA MUM(-1)) and the
      limit of detection decreased (11.10 to 0.65 MUM) as the dendrigraft generation
      increased from generation G2 through to generation G5, respectively. The results
      are compared to those for protein voltammetry at the ITIES. Our studies suggest
      that the sensitivity expected for a synthetic ionized macromolecule can be
      predicted on the basis of its net charge and its diffusion coefficient. However,
      electrochemistry at the ITIES demonstrates a greater sensitivity toward proteins,
      which is attributed to their tertiary structure.

PMID- 22642448
TI  - Breast cancer in men in Cote d'Or (France): epidemiological characteristics,
      treatments and prognostic factors.
AB  - Breast cancer in men is rare, and clinical trials are thus not feasible. This
      study aimed to describe the epidemiological characteristics, treatment and
      prognostic factors of breast cancer in men. A population-based study was
      performed using data from the Cote d'Or breast and gynaecological cancer
      registry. Data on male breast cancer diagnosed from 1982 to 2008 were provided.
      Relative survival rates were estimated at 5 years according to the
      characteristics of the patient and tumour, and treatment. Prognostic factors of
      survival in men with breast cancer were identified using a generalised linear
      model. Seventy-five men with invasive breast cancer were registered. Mean age at
      diagnosis was 66 years. The use of adjuvant chemotherapy (P= 0.013) and hormone
      therapy (P < 0.0001) increased over time. Relative survival rate at 5 years was
      69% for the whole population. Analysis of relative survival according to the
      treatment showed that survival was longer for patients treated with surgery +
      radiotherapy + hormone therapy: 89% at 5 years. Scarff, Bloom and Richardson
      grade was independent prognostic factor of survival. Male breast cancer is a rare
      disease with a poor prognosis, and diagnosis is often made at an advanced stage.
      Early diagnosis and better knowledge of the disease would certainly lead to
      improvements in the prognosis.

PMID- 22642449
TI  - First description of inhibition of let-7 microRNA expression and HMGA2
      overexpression in a case of deep-seated diffuse lipomatosis.

PMID- 22642450
TI  - Spin doping of individual molecules by using single-atom manipulation.
AB  - Being able to control the spin of magnetic molecules at the single-molecule level
      will make it possible to develop new spin-based nanotechnologies. Gate-field
      effects and electron and photon excitations have been used to achieve spin
      switching in molecules. Here, we show that atomic doping of molecules can be used
      to change the molecular spin. Furthermore, a scanning tunneling microscope was
      used to place or remove the atomic dopant on the molecule, allowing us to change
      the molecular spin in a controlled way. Bis(phthalocyaninato)yttrium (YPc(2))
      molecules deposited on an Au (111) surface keep their spin-1/2 magnetic moment
      due to the small molecule-substrate interaction. However, when Cs atoms were
      carefully placed onto YPc(2) molecules, the spin of the molecule vanished as
      shown by our conductance measurements and corroborated by the results of density
      functional theory calculations.

PMID- 22642451
TI  - Ultrasound guidance to approach the femoral nerve in the iliopsoas muscle: a
      preliminary study in the dog.
AB  - OBJECTIVE: To describe the location of the femoral nerve within the iliopsoas
      muscle and determine the feasibility and potential complications of an ultrasound
      guided block. STUDY DESIGN: Prospective experimental trial. ANIMALS: Sixteen
      adult dogs, median weight 14.3 (range 3-37) kg. METHODS: Phase I. Computed
      tomographic images of the iliopsoas muscle and femoral nerve were analyzed in two
      dogs. Phase II. The location of the femoral nerve within the iliopsoas muscle was
      determined via ultrasonography in 11 healthy anaesthetized dogs. Phase III.
      Peripheral nerve stimulation and ultrasound were combined to perform femoral
      nerve blocks in three dogs. RESULTS: Using computed tomography, the femoral nerve
      and its L4-L5 roots were identified within the iliopsoas muscle. The nerve itself
      was traced until it branched off into the quadriceps femoris muscle. Using
      ultrasonography, it was possible to observe the femoral nerve in nine dogs (82%).
      Starting at the dorsal third of the iliopsoas muscle, its path was traced in a
      caudo-ventro-lateral direction, emerging from the iliopsoas muscle shortly before
      passing through the muscular lacuna where it became very difficult to identify.
      An ultrasound-guided femoral nerve approach was carried out successfully in all
      three dogs. CONCLUSIONS: It is possible to approach the femoral nerve using
      combined ultrasound guidance and peripheral nerve stimulation to a closer
      proximal point than previously described. CLINICAL RELEVANCE: The ultrasound
      guided approach of the femoral nerve within the iliopsoas muscle has the
      potential to become an additional approach.

PMID- 22642452
TI  - Retrobulbar hemodynamics before and after oculopression with and without
      dorzolamide.
AB  - PURPOSE: To investigate the effect of intraocular pressure (IOP) reduction by
      oculopression and topical dorzolamide on retrobulbar hemodynamics. METHODS: Sixty
      patients (70 +/- 8.5) solely with cataract diagnosis solely were included in this
      prospective study. Patients with other systemic and ocular diseases affecting
      ocular circulation were excluded. On 30 patients (71 +/- 8.5), solely
      oculopression (Honan IOP reducer) was performed. The other half of the patients
      (69 +/- 8.3) additionally received 2 h prior to oculopression additionally
      topical dorzolamide. Before and after oculopression, IOP was measured and color
      Doppler imaging (CDI) was performed for the ophthalmic artery (OA), the central
      retinal artery, and the short posterior ciliary arteries (PCA). Furthermore,
      blood pressure and heart rate were monitored. RESULTS: At baseline there was no
      significant IOP difference between both groups (p = 0.54). IOP, measured prior to
      oculopression, was significant lower (p < 0.0001) in the group treated with
      dorzolamide (15.2 mmHg) compared to the other group (17.8 mmHg). Oculopression
      then led to a significant IOP reduction in all patients (p < 0.0001). There was
      no significant difference of the delta of IOP reduction between both groups
      observed (p = 0.47). In either group CDI showed a significant increase of peak
      systolic velocity (PSV) (p < 0.0001) and end-diastolic velocity (EDV) (p <
      0.0001) after oculopression in all vessels. In both groups ocular perfusion
      pressure increased significantly by 6% (p < 0.0001). After oculopression the PSV
      of the OA was significantly higher (14%; p < 0.0001) after dorzolamide
      application than after oculopression alone. Furthermore, in the group with
      oculopression and dorzolamide treatment EDV of the PCA was significantly higher
      (21%; p < 0.0001) and resistive index of the PCA was significantly lower (-5.6%;
      p = 0.001). CONCLUSION: IOP reduction by a pure mechanical procedure like
      oculopression leads to a significant increase of flow velocities of the
      retrobulbar vessels. This effect can significantly be increased by using
      dorzolamide prior to oculopression.

PMID- 22642453
TI  - Commentary for "Ultrasound guided foam therapy for treating incompetent great
      saphenous veins: results of 3-year analysis and morphologic evolvement study".

PMID- 22642454
TI  - Commentary on sclerotherapy of telangiectasias: a two-step, painless technique.

PMID- 22642455
TI  - Basal cell carcinoma: surgical margin detection using digital dermoscopy.

PMID- 22642456
TI  - Zinc oxide paste as sunscreen in the postoperative period.

PMID- 22642457
TI  - Ultraviolet-fluorescent tattoo for radiotherapy marking?

PMID- 22642458
TI  - Improving efficacy of liposculpture revisions using a short plastic tube as
      syringe connector.

PMID- 22642459
TI  - Three-minute chemosurgical biopsy site treatment for invasive cutaneous melanoma.

PMID- 22642460
TI  - Ingestion of foreign objects as a means of nonlethal self-injury.
AB  - The focus of this practice review is to understand the precursors, correlates,
      and treatment of self-injury by ingestion of foreign objects among patients in
      inpatient mental health facilities. These cases exhibited pervasive
      psychopathology of early onset, histories of severe personality disorder, and
      trauma. The cases seemingly presented a higher incidence of medical complications
      than is reported in the literature, and treatment outcomes varied from modest-to
      good success. Considering these difficulties, the goal of this practice review is
      to shed light on the motivation and treatment of self-injury by ingestion and to
      consider directions where existing theory and research could inform treatment
      strategies in future cases. We conclude the practice review with a summary of
      questions that remain to be answered with future research studies and make
      recommendations regarding treatment of these difficult cases.

PMID- 22642462
TI  - The Psychopathy Checklist-Revised (PCL-R), low anxiety, and fearlessness: a
      structural equation modeling analysis.
AB  - The current study employed a large representative sample of violent male
      offenders within the Swedish prison system to examine the factor structure of the
      PCL-R and the latent variable relations between the PCL-R items and clinical
      ratings of low trait anxiety and trait fearlessness (LAF). Consistent with
      previous research, confirmatory factor analysis (CFA) revealed strong support for
      the four-factor model of psychopathy (Interpersonal, Affective, Lifestyle, and
      Antisocial). Also, a series of CFAs revealed that the LAF items could be placed
      on any of the PCL-R factors without any changes in model fit. Finally, structural
      equation modeling results indicated that a PCL-R superordinate factor was able to
      account for most of the variance of a separate LAF factor. Taken together, the
      results indicate that if low anxiety and fearlessness, as measured via clinical
      ratings, are part of the psychopathy construct they are comprehensively accounted
      for by extant PCL-R items.

PMID- 22642461
TI  - Longitudinal twin study of borderline personality disorder traits and substance
      use in adolescence: developmental change, reciprocal effects, and genetic and
      environmental influences.
AB  - Although the comorbidity between borderline personality disorder (BPD) and
      substance abuse is well established, there are few longitudinal studies that have
      examined its developmental origins or whether the comorbidity is due to common
      genetic or environmental risk factors. To fill this gap, we used a large sample
      of female adolescent twins (N = 1,280) to examine the developmental course,
      reciprocal influences, and the genetic and environmental factors underlying the
      co-occurrence of BPD traits and substance use from age 14 to 18. Rank-order
      stability was moderate to high for both BPD traits (r = .58) and substance use (r
      = .51), whereas mean levels of substance use increased substantially from age 14
      to 18 (d = 0.77) and BPD traits showed a small decline (d = -0.21). BPD traits
      and substance use exhibited concurrent and prospective associations; however, the
      longitudinal associations dropped to nonsignificance after accounting for the
      temporal stability of each trait. Twin analyses revealed that shared
      environmental factors accounted for the association between BPD traits and
      substance use at age 14, but genetic factors accounted for the association at age
      18. These results indicate that, at least in adolescence, the comorbidity between
      BPD traits and substance use is a consequence of common risk factors rather than
      due to one being a casual antecedent of the other.

PMID- 22642463
TI  - Schizotypy, social cognition, and interpersonal sensitivity.
AB  - Social cognition in relation to schizophrenia liability remains largely uncharted
      terrain. Successful social interactions involve sensitivity to the feelings and
      behavior of others, and the ability to convey and communicate cues to elicit
      desired responses from others. Disruption in any part of this process will affect
      social interactions and functioning, including occupational functioning.
      Individuals who do better on tasks measuring interpersonal sensitivity are more
      interpersonally skilled and better adjusted (Hall, Andrzejewski, & Yopchick,
      2009), and those who perform poorly on tasks of interpersonal sensitivity, such
      as patients with schizophrenia, have known interpersonal and social functioning
      deficits (e.g., Toomey, Schuldberg, Corrigan, & Green, 2002). Schizotypic
      subjects were compared to depression vulnerable and normal control subjects on a
      well-established dynamic test of interpersonal sensitivity, the Profile of
      Nonverbal Sensitivity (PONS; Rosenthal, Hall, DiMatteo, Rogers, & Archer, 1979,
      2011). Results revealed a deficit for schizotypes relative to both the depression
      risk and normal control groups on the PONS. Our examination of the interpersonal
      sensitivity in schizotypes may shed light on the social functioning problems seen
      in patients with schizophrenia in a translational research framework.

PMID- 22642464
TI  - Considering the evidence and making the most empirically informed decision about
      depressive personality disorder in DSM-5.
AB  - In this paper, the criteria proposed by Kendler, Kupfer, Narrow, Philips, and
      Fawcett (2009) for the inclusion or exclusion of a diagnostic category in DSM-5
      are reviewed as they relate to the proposal of depressive personality disorder
      (DPD). Three options are offered as possible decisions for the future of DPD, and
      a discussion of the actual decision by the Personality and Personality Disorders
      Work Group is provided. Despite what may ultimately be the removal of the DPD
      type from the DSM-5, it is concluded that there is considerable support for DPD
      as a diagnostic category. Such a conclusion incorporates most coherently the
      empirical findings about the DPD proposal in a way that allows for ongoing
      empirical investigation of its biogenetic origins, its phenotypic manifestations
      (including its trait profile) and possible characterization as an endophenotype,
      and the clinical utility it appears to hold among clinicians.

PMID- 22642465
TI  - An item response theory analysis of the DSM-IV borderline personality disorder
      criteria in a population-based sample of 11- to 12-year-old children.
AB  - Although a growing body of empirical literature provides some support for the
      diagnosis of borderline personality disorder (BPD) in youth, little is known
      about the internal structure of BPD and the performance of the individual
      diagnostic criteria, especially in younger samples. We used item response theory
      (IRT) methods to investigate the psychometric properties of the Diagnostic and
      Statistical Manual of Mental Disorders, 4th edition (DSM-IV) BPD criteria in a
      large, population-based sample (n = 6,339) of young adolescents from the United
      Kingdom (ages 11 to 12). BPD was assessed using the Childhood Interview for DSM
      IV Borderline Personality Disorder (CI-BPD; Zanarini, Horwood, Waylen, & Wolke,
      2004). A single underlying dimension adequately accounted for covariation among
      the BPD criteria. Each criterion was found to be discriminating to a degree
      comparable to what has been reported in adult studies. BPD criteria were most
      informative within a range of severity of BPD pathology between +1 and +3
      standard units. Five criteria were found to exhibit differential item functioning
      (DIF) between boys and girls. However, DIF balanced out for the total interview
      score. Despite the controversy associated with applying the borderline construct
      to youth, the current findings provide psychometric evidence in favor of doing
      so.

PMID- 22642466
TI  - Use of multiparametric MR with neurovascular bundle evaluation to optimize the
      oncological and functional management of patients considered for nerve-sparing
      radical prostatectomy.
AB  - INTRODUCTION: To obtain the best results with radical prostatectomy, either from
      an oncological or a functional point of view, a correct selection of cases and
      planning of surgery are crucial. Multiparametric magnetic resonance imaging (MRI)
      promises to make it a successful imaging tool for improving many aspects of
      prostate cancer management. AIM: The aim of this study is to evaluate whether a
      modern multiparametric MRI can help either to better select prostate cancer cases
      for a nerve-sparing radical prostatectomy or to improve the functional evaluation
      related to neurovascular bundles preservation. MAIN OUTCOME MEASURES: The effect
      of preoperative MRI on neurovascular bundle management was examined for the
      frequency and the appropriateness of changes of the surgical plane on the basis
      of MRI indications. METHODS: In a prospective study, 125 consecutive patients
      with biopsy proven prostate cancer who were scheduled to undergo bilateral nerve
      sparing surgery. All patients included into the study were submitted to a
      preoperative multiparametric MRI. On the basis of MRI evaluation, patients were
      divided into two groups. Patients in group A were then submitted to a bilateral
      nerve-sparing (NS) radical prostatectomy (RP), whereas patients in group B were
      submitted to unilateral NS or non-NS RP. RESULTS: In group A, the confirmation
      from the MRI study to perform a bilateral NS procedure was appropriate in 70 of
      73 cases (95.9%), whereas in group B, the surgical plan was appropriate in 28 of
      32 cases (87.5%). On the contrary, MRI findings suggested a change in the initial
      surgical plan (group B) for 32 of 105 cases (30.5%). Of these 32 cases in group
      B, MRI suggested to perform a unilateral NS procedure in 21 of 32 cases (65.6%)
      and a non-NS procedure in 11 of 32 cases (34.4%). CONCLUSIONS: Multiparametric
      MRI analysis can significantly improve the standard selection and management of
      prostate carcinoma cases considered for an NS RP.

PMID- 22642467
TI  - Association between human cartilage glycoprotein 39 (YKL-40) and arterial
      stiffness in essential hypertension.
AB  - BACKGROUND: YKL-40, a proposed marker of inflammation and endothelial
      dysfunction, is associated with atherosclerosis and an increased cardiovascular
      mortality in the general population. However, the relationship between YKL-40 and
      arterial stiffness in hypertensive patients has not been adequately assessed.
      METHODS: The relationship between serum levels of YKL-40 and arterial stiffness
      was evaluated in 93 essential hypertensive subjects and 80 normal subjects.
      Essential hypertensive subjects were divided into two groups based upon urinary
      albumin-to-creatinine ratio (ACR): nonmicroalbuminuric group, (ACR <30 mg/g, n =
      50) and microalbuminuric group (ACR >= 30 mg/g, n = 43). Large artery wall
      stiffness was assessed by measuring femoral arterial stiffness and carotid
      femoral pulse wave velocity (cf-PWV). Serum levels of YKL-40 were determined by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: The study demonstrated that
      YKL-40,cf-PWV and femoral arterial stiffness were increased significantly
      (P<0.05) in the hypertensive group compared with normal controls. These
      measurements were also increased significantly ( P<0.05) in the microalbuminuric
      group compared with the nonmicroalbuminuric group. YKL-40 was positively
      correlated with cf-PWV( r = 0.44, P = 0.000) and femoral arterial stiffness ( r =
      0.42, P =0.001). Multiple linear stepwise regression analysis showed that YKL-40
      was the impact factor of arterial stiffness ( P<0.05). CONCLUSION: YKL-40 levels
      are elevated in essential hypertension subjects with an independent association
      between increasing YKL-40 levels and increasing arterial stiffness. The study
      suggests it played a positive role of YKL-40 in the progressing vascular
      complications in patients with essential hypertension.

PMID- 22642468
TI  - The AJT Report news and issues that affect organ and tissue transplantation.

PMID- 22642469
TI  - Memory T cells: new insights into the molecular basis of sensitivity and
      heterogeneity.

PMID- 22642470
TI  - The inside story of dendritic cell immunotherapy.

PMID- 22642471
TI  - Human T cell lymphotrophic virus 1 after transplantation: what is the risk of
      recipient disease?

PMID- 22642472
TI  - 21 years old-who cares?

PMID- 22642475
TI  - Abdominal pain, fever and free air one year post simultaneous pancreas-kidney
      transplant.

PMID- 22642473
TI  - Conversion from cyclosporine to everolimus at 4.5 months posttransplant: 3-year
      results from the randomized ZEUS study.
AB  - The long-term effect of conversion from calcineurin inhibitor (CNI) therapy to an
      mTOR inhibitor requires clarification. Following completion of the 12-month, open
      label, multicenter ZEUS study, in which 300 kidney transplant recipients were
      randomized to continue cyclosporine (CsA) or convert to everolimus at 4.5 months
      posttransplant, outcomes were assessed at month 36 (n = 284; 94.7%). CNI therapy
      was reintroduced in 28.4% of everolimus patients by month 36. The primary
      efficacy endpoint, estimated glomerular filtration rate (Nankivell, ANCOVA) was
      significantly higher with everolimus versus the CsA group at month 24 (7.6
      mL/min/1.73 m(2) , 95%CI 4.3, 11.0 mL/min/1.73 m(2) ; p < 0.001) and month 36
      (7.5 mL/min/1.73 m(2) , 95%CI 3.6, 11.4 mL/min/1.73 m(2) ; p < 0.001). The
      incidence of biopsy-proven acute rejection from randomization to month 36 was
      13.0% in the everolimus arm and 4.8% in the CsA arm (p = 0.015). Patient and
      graft survival, as well as incidences of malignancy, severe infections and
      hospitalization, were similar between groups. Kidney transplant patients who are
      converted from CsA to everolimus at month 4.5 and who remain on everolimus
      thereafter may achieve a significant improvement in renal function that is
      maintained to 3 years. There was a significantly higher rate of rejection in the
      everolimus arm but this did not exert a deleterious effect by 3 years
      posttransplant.

PMID- 22642477
TI  - Dynamic changes in serum angiopoietin-1, angiopoietin-2, and angiopoietin
      2/angiopoietin-1 ratio in acute myocardial infarction patients treated with
      primary percutaneous coronary intervention.
AB  - CONTEXT: Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) play divergent roles
      in myocardial ischemia and reperfusion injury. OBJECTIVE: To investigate serum
      Ang-1 and Ang-2 levels in ST-segment elevation myocardial infarction (STEMI)
      patients treated with primary percutaneous coronary intervention (PCI). METHODS:
      Serum Ang-1 and Ang-2 were measured in 85 STEMI patients in the first week after
      PCI. RESULTS: Ang-1, Ang-2 and Ang-2/Ang-1 ratio (Ang-2/1) were all increased at
      admission, and had dynamic changes after PCI. Ang-2 and Ang-2/1 at admission and
      2 h after PCI were positively correlated with peak cardiac troponin T levels.
      CONCLUSION: The extent of myocardial damage may be linked to circulating Ang-2
      and Ang-2/1.

PMID- 22642478
TI  - Improvement of Cencibel red wines by oxygen addition after malolactic
      fermentation: study on color-related phenolics, volatile composition, and sensory
      characteristics.
AB  - The objective of this paper was to check whether a micro-oxygenation technique
      applied after malolactic fermentation could improve the quality of Cencibel red
      wines. For that purpose, the color-related phenolics, volatile composition, and
      sensory characteristics during the micro-oxygenation treatment have been
      considered. The phenolic compounds more affected by the oxygen addition were
      hydroxycinnamic acids and their derivatives [(+)-catechin and (-)-epicatechin],
      flavonols (glycosilated forms), and anthocyanins-related pigments. The fact that
      the concentration of pyranoanthocyanins and hydroxyphenyl-pyranoanthocyanins was
      higher in treated red wines is closely related to their color stabilization. As a
      consequence, higher values of the yellow and red component of the color (b* and
      a*, respectively) were also observed in micro-oxygenated red wines. Red wine
      aroma quality was also improved in treated wines. A significant decrease in
      herbaceous notes, bitterness, acidity, and astringency was found, as well as
      higher scores of red fruits, plum, liquorice, and spicy attributes in oxygen
      added red wines. 

PMID- 22642479
TI  - Editorial (hot topic: functional significance of signaling proteins & peptides on
      apoptosis in cancer cells).

PMID- 22642480
TI  - Immunostaining in the context of loss mismatch repair function: interpretive
      confounders and cautionary tales!

PMID- 22642481
TI  - The social life of 'eugh': disgust as assessment in family mealtimes.
AB  - Disgust is a complex phenomenon that pervades a number of social situations. To
      date, disgust has primarily been understood as an individually experienced
      emotion or as a way of defining boundaries between people or objects; the
      detailed social practices through which disgust is choreographed, however, have
      yet to be fully explored. The social implications of disgust are particularly
      apparent when food and eating are involved, as it is in such settings that
      individuals, objects, and social boundaries coincide. In this paper, I argue that
      the enactment of disgust is an inherently social event, and that we can evidence
      it as such through the way in which it is produced and oriented to in everyday
      interaction. The setting for this paper is family mealtimes, as a situation in
      which children and parents explore the boundaries of what is, and what is not,
      disgusting. A large corpus of video and audio recordings of mealtimes in England
      and Scotland were analysed using a discursive psychological approach, with a
      focus on explicating the sequential and prosodic features of disgust markers
      (DMs), such as 'eugh' and 'yuck'. The analysis demonstrates that DMs are
      typically preceded by a 'noticing' by speakers and that 'eugh' is usually uttered
      alone and at the start of a turn in talk. It is argued that, regardless of their
      putative status as emotions or cultural concepts, DMs work as assessments of food
      and eating practices in everyday interaction. They orient others to a trouble
      source and attend to people's entitlements to 'know' disgust. The implications
      for our understanding of disgust as a social psychological concept are further
      explored. 

PMID- 22642482
TI  - To have and to hold: gratitude promotes relationship maintenance in intimate
      bonds.
AB  - This multimethod series of studies merges the literatures on gratitude and risk
      regulation to test a new process model of gratitude and relationship maintenance.
      We develop a measure of appreciation in relationships and use cross-sectional,
      daily experience, observational, and longitudinal methods to test our model.
      Across studies, we show that people who feel more appreciated by their romantic
      partners report being more appreciative of their partners. In turn, people who
      are more appreciative of their partners report being more responsive to their
      partners' needs (Study 1), and are more committed and more likely to remain in
      their relationships over time (Study 2). Appreciative partners are also rated by
      outside observers as relatively more responsive and committed during dyadic
      interactions in the laboratory, and these behavioral displays are one way in
      which appreciation is transmitted from one partner to the other (Study 3). These
      findings provide evidence that gratitude is important for the successful
      maintenance of intimate bonds.

PMID- 22642483
TI  - Boosting beauty in an economic decline: mating, spending, and the lipstick
      effect.
AB  - Although consumer spending typically declines in economic recessions, some
      observers have noted that recessions appear to increase women's spending on
      beauty products--the so-called lipstick effect. Using both historical spending
      data and rigorous experiments, the authors examine how and why economic
      recessions influence women's consumer behavior. Findings revealed that
      recessionary cues--whether naturally occurring or experimentally primed-
      decreased desire for most products (e.g., electronics, household items). However,
      these cues consistently increased women's desire for products that increase
      attractiveness to mates--the first experimental demonstration of the lipstick
      effect. Additional studies show that this effect is driven by women's desire to
      attract mates with resources and depends on the perceived mate attraction
      function served by these products. In addition to showing how and why economic
      recessions influence women's desire for beauty products, this research provides
      novel insights into women's mating psychology, consumer behavior, and the
      relationship between the two.

PMID- 22642484
TI  - Individual differences in ideological attitudes and prejudice: evidence from peer
      report data.
AB  - Our knowledge on the personality basis of ideological attitudes and prejudice,
      while based on a substantial body of research, suffers from a potentially serious
      methodological limitation: an overreliance on the method of self-reports. Across
      2 studies (Ns = 193, 424), we examined associations between the Big Five
      personality dimensions, Right-Wing Authoritarianism (RWA), Social Dominance
      Orientation (SDO), and generalized prejudice, using both self-report and peer
      report data stemming from 1 (Study 1) or 2 (Study 2) peer rater/s. Correlational
      and regression analyses as well as structural equation modeling showed that (a)
      the associations between personality dimensions, ideological attitudes, and
      prejudice were largely similar to previous research for both data sources; (b)
      RWA and prejudice showed a similar level of self-peer agreement to personality
      dimensions; (c) most of the known associations between personality, ideological
      attitudes, and prejudice were replicated also when measured by independent
      methods; (d) peer reports had some incremental validity in predicting ideological
      attitudes and prejudice; and (e) there was evidence that Openness to Experience
      and Agreeableness predicted prejudice directly and not only indirectly via RWA
      and SDO, respectively. Implications for the status of RWA, SDO, and prejudice as
      individual-difference constructs and for their bases in personality dimensions
      are discussed.

PMID- 22642485
TI  - Sweeping dishonesty under the rug: how unethical actions lead to forgetting of
      moral rules.
AB  - Dishonest behavior can have various psychological outcomes. We examine whether
      one consequence could be the forgetting of moral rules. In 4 experiments,
      participants were given the opportunity to behave dishonestly, and thus earn
      undeserved money, by over-reporting their performance on an ability-based task.
      Before the task, they were exposed to moral rules (i.e., an honor code). Those
      who cheated were more likely to forget the moral rules after behaving
      dishonestly, even though they were equally likely to remember morally irrelevant
      information (Experiment 1). Furthermore, people showed moral forgetting only
      after cheating could be enacted but not before cheating (Experiment 2), despite
      monetary incentives to recall the rules accurately (Experiment 3). Finally, moral
      forgetting appears to result from decreased access to moral rules after cheating
      (Experiment 4).

PMID- 22642486
TI  - Minimum infusion rates and recovery times from different durations of continuous
      infusion of fospropofol, a prodrug of propofol, in rabbits: a comparison with
      propofol emulsion.
AB  - OBJECTIVE: To explore, in rabbits, the minimum infusion rates (MIR) required and
      recovery time from long duration (<= 8 hours) continuous infusion of fospropofol
      disodium, a novel water-soluble prodrug of propofol, and compare it with
      propofol. STUDY DESIGN: Prospective, randomized, blinded experimental trial.
      ANIMALS: Ninety-six adult laboratory rabbits, mean +/- SD weight 2.20 +/- 0.15
      kg. METHODS: Stage 1. 16 rabbits were assigned to receive fospropofol disodium or
      propofol to measure MIR, using an up-and-down method with response to tail
      clamping stimulus (TCS). Stage 2. Eighty rabbits were allocated to group F
      (fospropofol disodium) or group P (propofol), and further subdivided (n = 10 in
      each subgroup) according to infusion time (2, 4, 6 or 8 hours), to groups F(2h),
      F(4h), F(6h), F(8h) and P(2h), P(4h), P(6h), P(8h). Fospropofol or propofol were
      infused, and tail clamping applied to maintain the same depth of anaesthesia
      until infusion was completed. Times to recover righting reflex (RR), to respond
      to TCS, and total recovery to different durations of continuous infusion of two
      anaesthetic drugs were noted. Respiratory and pulse rates and oxygen saturation
      were analyzed. The plasma concentrations of fospropofol disodium, the active
      metabolite propofol (propofol(F) ) and propofol emulsion were measured with
      respect to loss and recovery of RR and TCS. RESULTS: MIR of fospropofol disodium
      was 2.0 mg kg(-1) minute(-1) , and MIR of propofol was 0.9 mg kg(-1) minute(-1) .
      Times in minutes to total recovery from anaesthesia in groups F and P were as
      follows, F(2h) 15 +/- 3; F(4h) 26 +/- 4; F(6h) 52 +/- 6; F(8h) 84 +/- 10; and
      P(2h) 10 +/- 1; P(4h) 19 +/- 7; P(6h) 36 +/- 7; P(8h) 48 +/- 5. CONCLUSIONS AND
      CLINICAL RELEVANCE: After continuous intravenous infusion in rabbits (<= 8
      hours), fospropofol disodium and propofol both show an extension of recovery time
      with increasing infusion time, fospropofol disodium showing a significantly
      greater prolongation compared to propofol emulsion when infusion time increases
      to 6 and 8 hours.

PMID- 22642487
TI  - Can common hepatic artery lymph node dissection be safely omitted in surgery for
      clinical T1N0 thoracic esophageal squamous cell carcinoma?
AB  - Common hepatic artery lymph node dissection is regarded as a standard procedure
      in esophageal cancer surgery because of aggressive lymphatic dissemination of
      esophageal cancer. However, lymph node dissection can prolong operation time and
      may be associated with complications such as chylous ascites. Here, we aimed to
      evaluate the effectiveness of common hepatic artery lymph node dissection in
      clinical T1N0 thoracic esophageal squamous cell carcinoma. Between 1996 and 2009,
      1390 patients underwent surgery for esophageal cancer in our institution, and 209
      were found to have clinical T1N0 disease. Exclusion criteria were nonsquamous
      carcinoma, double primary cancer, definite distant metastasis, administration of
      neoadjuvant treatment, and incomplete abdominal lymph node dissection. We
      retrospectively analyzed medical records, operative and pathologic data, and
      follow-up information. Forty-two patients were excluded from the study. Among the
      167 enrolled patients, preoperative endoscopic ultrasound evaluation was
      performed in 160 patients. Fifty-two patients had distal esophageal or
      esophagogastric junction tumor. Surgery included 2 cases of tri-incisional
      esophagectomy, 17 cases of transhiatal esophagectomy, and 148 cases of two-field
      esophagectomy (Ivor Lewis operation). Common hepatic artery lymph node dissection
      was performed in all cases, and none of the patients had metastasis. Mean follow
      up period was 35.4 +/- 28.7 months. In-hospital mortality was one, and 5-year
      survival rate was 80.6%. Among the 15 patients with recurrence, there were two
      distant metastases and five distant and local recurrences but no intra-abdominal
      recurrence with common hepatic artery lymph node. Common hepatic artery lymph
      node dissection may be safely omitted in surgery for clinical T1N0 esophageal
      squamous cell carcinoma when preoperative evaluations including chest computed
      tomography, positron emission tomography and computed tomography, and
      esophagogastroduodenoscopy or endoscopic ultrasound are performed.

PMID- 22642488
TI  - Electromagnetic torque tweezers: a versatile approach for measurement of single
      molecule twist and torque.
AB  - The well-established single-molecule force-spectroscopy techniques have recently
      been complemented by methods that can measure torque and twist directly, notably
      magnetic torque tweezers and the optical torque wrench. A limitation of the
      current torque measurement schemes is the intrinsic coupling between the force
      and torque degrees of freedom. Here we present electromagnetic torque tweezers
      (eMTT) that combine permanent and electromagnets to enable independent control of
      the force and torsional trap stiffness for sensitive measurements of single
      molecule torque and twist. Using the eMTT, we demonstrate sensitive torque
      measurements on tethered DNA molecules from simple tracking of the beads' (x,y)
      position, obviating the need for any angular tracking algorithms or markers.
      Employing the eMTT for high-resolution torque measurements, we experimentally
      confirm the theoretically predicted torque overshoot at the DNA buckling
      transition in high salt conditions. We envision that the flexibility and control
      afforded by the eMTT will enable a range of new torque and twist measurement
      schemes from single-molecules to living cells.

PMID- 22642489
TI  - Addressing the aging crisis in U.S. criminal justice health care.
AB  - The U.S. criminal justice population is aging at a significantly more rapid rate
      than the overall U.S. population, with the population of older adults in prison
      having more than tripled since 1990. This increase is at the root of a prison
      healthcare crisis that is spilling into communities and public healthcare systems
      because nearly 95% of prisoners are eventually released. The graying prison
      population is also straining state and local budgets. In prison, older prisoners
      cost approximately three times as much as younger prisoners to incarcerate,
      largely because of healthcare costs. In the community, older former prisoners
      present the least risk of recidivism yet are vulnerable to serious and costly
      social and medical challenges such as housing instability, poor employability,
      multiple chronic health conditions, and health-related mortality; however older
      current and former prisoners are largely ignored in the current geriatrics
      evidence base. Knowledge about the health, functional, and cognitive status of
      older prisoners is limited, with even less known about risk factors for long-term
      poor health outcomes during and after incarceration. This article provides an
      overview of aging in the criminal justice system. It then describes how geriatric
      models of care could be adapted to address the mounting older prisoner healthcare
      crisis and identifies areas where additional research is needed to explore prison
      specific models of care for older adults.

PMID- 22642490
TI  - Something from nothing: enhancing electrochemical charge storage with cation
      vacancies.
AB  - The performance of electrochemical energy storage devices (e.g., batteries and
      electrochemical capacitors) is largely determined by the physicochemical
      properties of the active electrode materials, such as the thermodynamic potential
      associated with the charge-storage reaction, ion-storage capacity, and long-term
      electrochemical stability. In the case of mixed ion/electron-conducting metal
      oxides that undergo cation-insertion reactions, the presence of cation vacancies
      in the lattice structure can enhance one or more of these technical parameters
      without resorting to a drastic change in material composition. Examples of this
      enhancement include the charge-storage properties of certain cation-deficient
      oxides such as gamma-MnO2 and gamma-Fe2O3 relative to their defect-free
      analogues. The optimal cation-vacancy fraction is both material- and application
      dependent because cation vacancies enhance some materials properties at the
      expense of others, potentially affecting electronic conductivity or thermal
      stability. Although the advantages of structural cation vacancies have been known
      since at least the mid-1980s, only a handful of research groups have purposefully
      integrated cation vacancies into active electrode materials to enhance device
      performance. Three protocols are available for the incorporation of cation
      vacancies into transition metal oxides to improve performance in both aqueous and
      nonaqueous energy storage. Through a processing approach, researchers induce
      point defects in conventional oxides using traditional solid-state-ionics
      techniques that treat the oxide under appropriate atmospheric conditions with a
      driving force such as temperature. In a synthetic approach, substitutional doping
      of a highly oxidized cation into a metal-oxide framework can significantly
      increase cation-vacancy content and corresponding charge-storage capacity. In a
      scaling approach, electrode materials that are expressed in morphologies with
      high surface areas, such as aerogels, contain more defects because the increased
      fraction of surface sites favors the formation of cation vacancies. In this
      Account, we review studies of cation-deficient electrode materials from the
      literature and our laboratory, focusing on transition metal oxides and the impact
      cation vacancies have on electrochemical performance. We also discuss the
      challenges and limitations of these defective structures and their promise as
      battery materials. 

PMID- 22642491
TI  - Evidence for kidney rejection after combined bone marrow and renal
      transplantation despite ongoing whole-blood chimerism in rhesus macaques.
AB  - Although there is evidence linking hematopoietic chimerism induction and solid
      organ transplant tolerance, the mechanistic requirements for chimerism-induced
      tolerance are not clearly elucidated. To address this, we used an MHC-defined
      primate model to determine the impact of impermanent, T cell-poor, mixed
      chimerism on renal allograft survival. We compared two cohorts: one receiving a
      bone marrow and renal transplant ("BMT/renal") and one receiving only a renal
      transplant. Both cohorts received maintenance immunosuppression with CD28/CD40
      directed costimulation blockade and sirolimus. As previously demonstrated, this
      transplant strategy consistently induced compartmentalized donor chimerism,
      (significant whole-blood chimerism, lacking T cell chimerism). This chimerism was
      not sufficient to prolong renal allograft acceptance: the BMT/renal mean survival
      time (MST, 76 days) was not significantly different than the renal transplant
      alone MST (85 days, p = 0.46), with histopathology documenting T cell mediated
      rejection. Flow cytometric analysis revealed significant enrichment for CD28
      /CD95+ CD4+ and CD8+ Tem cells in the rejected kidney, suggesting a link between
      CD28-negative Tem and costimulation blockade-resistant rejection. These results
      suggest that in some settings, transient T cell-poor chimerism is not sufficient
      to induce tolerance to a concurrently placed renal allograft and that the
      presence of this chimerism per se is not an independent biomarker to identify
      tolerance.

PMID- 22642493
TI  - Lack of correlation between blood lead and serum prolactin levels among lead
      exposed workers.
AB  - A cross sectional case (241 males occupationally exposed to lead)-control (102
      males unexposed to lead) study was performed with the aim of evaluating the
      relationship between serum prolactin (S-PRL) and lead blood (PbB) levels. A meta
      analysis of S-PRL levels in similar studies was also carried out. No difference
      of S-PRL between groups or any relationship between PbB and S-PRL levels was
      found. The meta-analysis showed a slight increase of S-PRL levels among exposed
      people, the weighted means falling within the reference values of the biomarker.
      The results do not support a routine use of S-PRL as a biomarker of effect in
      lead exposed workers.

PMID- 22642492
TI  - Depressive traits in essential tremor: impact on disability, quality of life, and
      medication adherence.
AB  - BACKGROUND: There is growing study of the psychiatric features of essential
      tremor. Depressive symptoms occur in a considerable number of patients. Yet their
      impact, as a primary factor, has received almost no attention. We assessed
      whether, independent of tremor severity, patients with more depressive symptoms
      have more perceived tremor-related disability, lower tremor-related quality of
      life, and poorer compliance with tremor medication. METHODS: On the basis of
      their Center for Epidemiological Studies Depression Scale score, we stratified 70
      essential tremor patients into three groups: 41 with minimal depressive symptoms,
      24 with moderate depressive symptoms, and five with severe depressive symptoms.
      Importantly, the three groups had similar tremor severity on neurological
      examination. We assessed self-reported tremor-related disability, tremor-related
      quality of life (Quality of Life in Essential Tremor) (QUEST) score, and
      medication compliance. RESULTS: Cases with minimal depressive symptoms had the
      lowest QUEST scores (i.e., highest quality of life), cases with moderate
      depressive symptoms had intermediate scores, and those with severe depressive
      symptoms had the highest QUEST scores (i.e., lowest quality of life) (P < 0.001).
      Depressive symptoms were a stronger predictor of tremor-related quality of life
      than was the main motor feature of essential tremor (ET) itself (tremor). Self
      reported medication compliance was lowest in cases with severe depressive
      symptoms and highest in cases with minimal depressive symptoms. CONCLUSIONS: The
      physical disability caused by the tremor of ET has traditionally been regarded as
      the most important feature of the disease that causes distress, and it has
      received the most attention in the management of patients with this disease. Our
      data indicate that this may not be the case.

PMID- 22642494
TI  - Large gradient high magnetic field affects FLG29.1 cells differentiation to form
      osteoclast-like cells.
AB  - PURPOSE: We aimed to investigate the effects of different apparent gravities (MU
      g, 1 g and 2 g) produced by large gradient high magnetic field (LGHMF) on human
      preosteoclast FLG29.1 cells. MATERIALS AND METHODS: FLG29.1 cells were cultured
      in Roswell Park Memorial Institute (RPMI)-1640 medium. Cells were exposed to
      LGHMF for 72 h. On culture day 1, 2, 3, cell proliferation was detected by 3
      (4,5)-dimethylthiahi-azo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method. On
      day 3, cell apoptosis and necrosis were assayed by Hoechst and propidium iodide
      (PI) staining. After cells were exposed to LGHMF for 72 h with the induction of
      12-o-tetradecanoylphorbol 13-acetate (TPA), Tartrate-Resistant Acid Phosphatase
      (TRAP) positive cells and nitric oxide (NO) release were detected by TRAP
      staining and Griess method, respectively. Intracellular TRAP activity was
      measured using nitrophenylphosphate (pNPP) as the substrate. RESULTS: MTT
      detection revealed that compared to control, FLG 29.1 cell proliferation in the
      MU g and 2 g groups were promoted. However, there is no obvious difference
      between the 1 g and control groups. Hoechst-PI staining showed that LGHMF
      promoted cell apoptosis and necrosis, especially in the 2 g group. Exposure to
      LGHMF inhibited the NO concentration of supernatant. Both the TRAP activity and
      the number of TRAP positive cells were higher in cells of MU g group than those
      in 2 g group. In the 1 g group, they were decreased significantly compared to
      control. CONCLUSIONS: These findings indicate that LGHMF could directly affect
      human preosteoclast FLG29.1 cells survival and differentiation. High magnetic
      flux inhibited osteoclasts formation and differentiation while reduced apparent
      gravity enhanced osteoclastogenesis.

PMID- 22642495
TI  - Anti-inflammatory property of n-hexadecanoic acid: structural evidence and
      kinetic assessment.
AB  - Ester bond hydrolysis of membrane phospholipids by Phospholipase A(2) and
      consequent release of fatty acids are the initiating steps of inflammation. It is
      proposed in this study that the inhibition of phospholipase A(2) is one of the
      ways to control inflammation. Investigations are carried out to identify the mode
      of inhibition of phospholipase A(2) by the n-hexadecanoic acid. It may help in
      designing of specific inhibitors of phospholipase A(2) as anti-inflammatory
      agents. The enzyme kinetics study proved that n-hexadecanoic acid inhibits
      phospholipase A(2) in a competitive manner. It was identified from the crystal
      structure at 2.5 A resolution that the position of n-hexadecanoic acid is in the
      active site of the phospholipase A(2). The binding constant and binding energy
      have also been calculated using Isothermal Titration Calorimetry. Also, the
      binding energy of n-hexadecanoic acid to phospholipase A(2) was calculated by in
      silico method and compared with known inhibitors. It may be concluded from the
      structural and kinetics studies that the fatty acid, n-hexadecanoic acid, is an
      inhibitor of phospholipase A(2), hence, an anti-inflammatory compound. The
      inferences from the present study validate the rigorous use of medicated oils
      rich in n-hexadecanoic acid for the treatment of rheumatic symptoms in the
      traditional medical system of India, Ayurveda.

PMID- 22642496
TI  - Acquired lymphangiectasia of the vulva.

PMID- 22642497
TI  - A biomechanical evaluation of a Hybrid Dynamic Compression Plate and a CastLess
      Arthrodesis Plate for pancarpal arthrodesis in dogs.
AB  - OBJECTIVE: To determine mechanical differences between two plates with different
      requirements for supplementary casting after pancarpal arthrodesis (PCA): the
      Veterinary Instrumentation Hybrid Dynamic Compression Plate (HDCP), and the
      OrthoMed CastLess Arthrodesis Plate (CLP). STUDY DESIGN: In vitro mechanical
      analysis. SAMPLE POPULATION: HDCP(n = 10), CLP(10). METHODS: Single-cycle load to
      failure using a materials-testing machine and cyclic loading between 38 and 380 N
      +/- 5% to simulate estimated in vivo loads until failure or 10(6) cycles.
      RESULTS: Single-cycle to failure: bending stiffness was significantly higher for
      the HDCP(2269 +/- 175 N/mm) than CLP(1754 +/- 88 N/mm; P < .001). Bending
      structural stiffness was higher for the HDCP(3.8 +/- 0.3 Nm(2) ) versus CLP(2.9
      +/- 0.2 Nm(2) ; P= .0022). A difference between the 2 plates for bending strength
      was not demonstrated; HDCP= 13.9 +/- 1.4 Nm, CLP13.2 +/- 0.5 Nm (P= .24). Cyclic
      Loading: no failures occurred with either plate type when plates were cycled to
      10(6) cycles. CONCLUSION: There is no mechanical advantage in bending resistance
      afforded by the CLPover the HDCP. Fatigue failure of either plate during the
      convalescent period of an estimated 150,000-250,000 cycles is unlikely. Based on
      the bending performance, there is no evidence to support the use of the CLPover
      the HDCPfor castless PCA.

PMID- 22642498
TI  - Cyclo-oxygenase inhibitors in the treatment of chronic non-infectious, non
      necrotizing scleritis and episcleritis.
AB  - PURPOSE: To evaluate the use of selective vs. non-selective cyclo-oxygenase
      inhibitors (COXIs) for the treatment of chronic non-infectious, non-necrotizing
      scleritis and episcleritis. METHODS: Sixty-nine patients with scleritis and
      episcleritis treated for >=2 months with COXIs were included. Outcome measures
      were rates of inflammation control, corticosteroid sparing, and COXI
      discontinuation, as well as side effects. RESULTS: Initial inflammation control
      was achieved in 78-81% of scleritis patients and 73-80% episcleritis patients on
      COXIs (p > .05). Rates of steroid sparing after 4-24 months of consecutive
      treatment were similar. Gastrointestinal side effects were observed in 1 (2.7%)
      patient on selective vs. 3 (9.4%) patients on non-selective COXIs (p = .33).
      Overall discontinuation rate was 6/37 (16%) for selective vs. 7/32 (22%) for non
      selective COXIs (p = .76). CONCLUSIONS: Selective vs. non-selective COXIs were
      equally efficacious for the treatment of chronic non-infectious, non-necrotizing
      scleritis and episcleritis. Prospective studies to elucidate potential
      differences in side effect profiles may be warranted.

PMID- 22642499
TI  - Plasma pharmacokinetics and pharmacodynamics of alfaxalone in neonatal foals
      after an intravenous bolus of alfaxalone following premedication with butorphanol
      tartrate.
AB  - OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of the
      neurosteroid anaesthetic, alfaxalone, in neonatal foals after a single
      intravenous (IV) injection of alfaxalone following premedication with butorphanol
      tartrate. STUDY DESIGN: Prospective experimental study. ANIMALS: Five clinically
      healthy Australian Stock Horse foals of mean +/- SD age of 12 +/- 3 days and
      weighing 67.3 +/- 12.4 kg. METHODS: Foals were premedicated with butorphanol
      (0.05 mg kg(-1) IV) and anaesthesia was induced 10 minutes later by IV injection
      with alfaxalone 3 mg kg(-1) . Cardiorespiratory variables (pulse rate,
      respiratory rate, direct arterial blood pressure, arterial blood gases) and
      clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous
      blood samples were collected at strategic time points and alfaxalone plasma
      concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS)
      and analysed by noncompartmental pharmacokinetic analysis. RESULTS: The harmonic,
      mean +/- SD plasma elimination half life (t1/2) for alfaxalone was 22.8 +/- 5.2
      minutes. The observed mean plasma clearance (Cl(p) ) and volume of distribution
      (Vd) were 19.9 +/- 5.9 mL minute kg(-1) and 0.6 +/- 0.2 L kg(-1) , respectively.
      Overall, the quality of the anaesthetic inductions and recoveries was good and
      most monitored physiological variables were clinically acceptable in all foals,
      although some foals became hypoxaemic for a short period following recumbency.
      The mean durations of anaesthesia from induction to first movement and from
      induction to standing were 18.7 +/- 7 and 37.2 +/- 4.7 minutes, respectively.
      CONCLUSIONS: The anaesthetic protocol used provided a predictable and consistent
      plane of anaesthesia in the five foals studied, with minimal cardiovascular
      depression. In foals, as in the adult horse, alfaxalone has a short elimination
      half life. CLINICAL RELEVANCE: Alfaxalone appears to be an adequate anaesthetic
      induction agent in foals and the pharmacokinetics suggest that, with continuous
      infusion, it might be suitable to provide more prolonged anaesthesia. Oxygen
      supplementation is recommended.

PMID- 22642500
TI  - Synthesis and utility of beta-selenol-phenylalanine for native chemical ligation
      deselenization chemistry.
AB  - An efficient synthetic route to a suitably protected beta-selenol-phenylalanine
      derivative from commercially available Garner's aldehyde is described. The
      incorporation of this building block into peptides and its application in native
      chemical ligation reactions with peptide thioesters are demonstrated. Ligation
      products were chemoselectively deselenized (including in the presence of
      unprotected cysteine residues) to provide native peptides.

PMID- 22642501
TI  - Effect of bolus taste on the esophageal transit of patients with stroke.
AB  - Stroke is a frequent cause of oropharyngeal dysphagia but may also cause
      alterations in esophageal motility. The aim of this investigation was to evaluate
      the effect of bolus taste on the esophageal transit of patients with stroke and
      controls. Esophageal transit and clearance were evaluated by scintigraphy in 36
      patients in the chronic phase of stroke (44-82 years, mean: 63 years) and in 30
      controls (33-85 years, mean: 59 years). The patients had a stroke 1-84 months
      (median: 5.5 months) before the evaluation of esophageal transit. Eight had
      dysphagia. Each subject swallowed in random order and in the sitting position 5
      mL of liquid boluses with bitter (pH=6.0), sour (pH=3.0), sweet (pH=6.9), and
      neutral (pH=6.8) taste. Transit and clearance duration and the amount of residues
      were measured in the proximal, middle, and distal esophageal body. There was no
      difference between patients and controls in esophageal transit or clearance
      duration. In the distal esophagus, the transit and clearance durations were
      longer with the sour bolus than with the other boluses in both patients and
      controls. The amount of residues in the esophageal body was greater in patients
      than in controls after swallows of the neutral bolus. In control subjects, after
      swallows of a sour bolus, there was an increase in the amount of residues in the
      middle and distal esophagus compared with the other boluses. In conclusion, a
      sour bolus with low pH causes a longer transit and clearance duration in the
      distal esophageal body. There was no effect of bolus taste or pH on the
      esophageal transit of patients in the chronic phase of stroke compared with
      normal volunteers. The longer transit and clearance duration in the distal
      esophageal body with the sour bolus appears to be a consequence of the low pH of
      the bolus.

PMID- 22642502
TI  - Detection of microbleeds in post-mortem brains of patients with frontotemporal
      lobar degeneration: a 7.0-Tesla magnetic resonance imaging study with
      neuropathological correlates.
AB  - BACKGROUND: Microbleeds (MBs) are frequently detected in brains of patients with
      Alzheimer dementia and rare in those with frontotemporal lobar degeneration
      (FTLD). This study investigates for the first time the topographic distribution
      of MBs on a T2*-weighted gradient-echo 7.0-T magnetic resonance imaging (MRI) in
      post-mortem FTLD brains. PATIENTS AND METHODS: The neuropathological and MRI
      findings in 12 FTLD brains were compared with eight age-matched controls. The
      presence of cerebrovascular lesions was evaluated on a coronal section of a
      cerebral hemisphere at the level of the mamillary body and on a horizontal
      section through pons and cerebellum. On MRI, the distribution and the number of
      cortical focal signal intensity losses, representing MBs, were assessed on
      coronal sections at the frontal, the central and the occipital level of a
      cerebral hemisphere. RESULTS: Overall, cerebrovascular lesions were rare. Only
      white matter damage was significantly more severe in FTLD brains compared with
      controls (P = 0.03). On MRI, MBs were only significantly prevalent in the deep
      cortical layers (P < 0.01) and borderline increased in the middle cortical layers
      (P = 0.07) of the frontal section. CONCLUSIONS: Cerebrovascular lesions are rare
      in FTLD. The white matter damage has to be considered as part of the
      neurodegenerative process. MBs prevail in the frontal regions with the most
      severe neuronal damage and probably represent associated disruption of the blood
      brain barrier.

PMID- 22642504
TI  - Modeling the binding affinity of p38alpha MAP kinase inhibitors by partial least
      squares regression.
AB  - The p38 mitogen-activated protein kinase is activated by environmental stress and
      cytokines and plays a role in transcriptional regulation and inflammatory
      responses. Factors influencing the activity and selectivity of the p38alpha
      mitogen-activated protein kinase inhibitors have been investigated in this paper
      by inspecting the binding orientation and the possible residue-inhibitor
      interactions in the binding site. The binding pattern of a set of 45 different
      inhibitors against p38alpha mitogen-activated protein kinase was studied through
      Molecular Dynamic Simulations of the protein-inhibitor complexes. Further,
      Partial Least Squares regression was used to develop a Quantitative Structure
      Activity Relationship model to predict the binding affinities of ligands. The
      selected model successfully predicted the test set with a Root Mean Square Error
      of Prediction of 1.36. The regression coefficients and the Variable Importance in
      Projection plots highlighted the residue-inhibitor interactions which exhibited
      the largest absolute effect on the ligand binding, such as the van der Waals
      interaction with LYS50, ILE81, ASP165; electrostatic interactions with SER29,
      LEU164; hydrogen bonds with MET106; and total energy interaction with SER29 and
      LEU83.

PMID- 22642505
TI  - Beta-blockers in intensive care medicine: potential benefit in acute brain injury
      and acute respiratory distress syndrome.
AB  - Sympathetic activation is a well-known phenomenon after acute brain injury and in
      critical illness. In this review we describe pathophysiological considerations
      that may help in elucidating the potential role of beta (beta)-adrenergic
      antagonists to block some of the adverse sympathetic effects in acute brain
      injury (subarachnoid hemorrhage and traumatic brain injury) and the acute
      respiratory distress syndrome. In acute brain injury cardiac dysfunction has been
      studied most extensively but its pathophysiology is only partly elucidated in
      man. Further, several adverse consequences of sympathetic activation on the brain
      itself may occur. Clinical and preclinical studies are described in this review
      that lend support to the idea that beta blockers may have beneficial effects on
      both cardiac, cerebral and other adverse consequences of sympathetic
      overactivation after acute brain injury. Second, the acute respiratory distress
      syndrome (ARDS) may also respond to beta blocker therapy, albeit through a
      different mechanism than in acute brain injury. Some studies reported on
      beneficial effects of these drugs on ARDS through the mitigation of pulmonary
      blood flow, without a decrease in systemic hemodynamics. However, in both acute
      brain injury and ARDS further studies are needed to distinguish those patients
      who are most likely to benefit from beta blockers from those more likely to be
      harmed by them. Furthermore, recent patents of beta blockers relevant to the
      content of this paper are referenced.

PMID- 22642503
TI  - Spatially-interactive biomolecular networks organized by nucleic acid
      nanostructures.
AB  - Living systems have evolved a variety of nanostructures to control the molecular
      interactions that mediate many functions including the recognition of targets by
      receptors, the binding of enzymes to substrates, and the regulation of enzymatic
      activity. Mimicking these structures outside of the cell requires methods that
      offer nanoscale control over the organization of individual network components.
      Advances in DNA nanotechnology have enabled the design and fabrication of
      sophisticated one-, two- and three-dimensional (1D, 2D, and 3D) nanostructures
      that utilize spontaneous and sequence-specific DNA hybridization. Compared with
      other self-assembling biopolymers, DNA nanostructures offer predictable and
      programmable interactions and surface features to which other nanoparticles and
      biomolecules can be precisely positioned. The ability to control the spatial
      arrangement of the components while constructing highly organized networks will
      lead to various applications of these systems. For example, DNA nanoarrays with
      surface displays of molecular probes can sense noncovalent hybridization
      interactions with DNA, RNA, and proteins and covalent chemical reactions. DNA
      nanostructures can also align external molecules into well-defined arrays, which
      may improve the resolution of many structural determination methods, such as X
      ray diffraction, cryo-EM, NMR, and super-resolution fluorescence. Moreover, by
      constraint of target entities to specific conformations, self-assembled DNA
      nanostructures can serve as molecular rulers to evaluate conformation-dependent
      activities. This Account describes the most recent advances in the DNA
      nanostructure directed assembly of biomolecular networks and explores the
      possibility of applying this technology to other fields of study. Recently,
      several reports have demonstrated the DNA nanostructure directed assembly of
      spatially interactive biomolecular networks. For example, researchers have
      constructed synthetic multienzyme cascades by organizing the position of the
      components using DNA nanoscaffolds in vitro or by utilizing RNA matrices in vivo.
      These structures display enhanced efficiency compared with the corresponding
      unstructured enzyme mixtures. Such systems are designed to mimic cellular
      function, where substrate diffusion between enzymes is facilitated and reactions
      are catalyzed with high efficiency and specificity. In addition, researchers have
      assembled multiple choromophores into arrays using a DNA nanoscaffold that
      optimizes the relative distance between the dyes and their spatial organization.
      The resulting artificial light-harvesting system exhibits efficient cascading
      energy transfers. Finally, DNA nanostructures have been used as assembly
      templates to construct nanodevices that execute rationally designed behaviors,
      including cargo loading, transportation, and route control.

PMID- 22642506
TI  - Palliative care teaching in medical residency: a review of two POGO-e teaching
      products.
AB  - This is a comparison review of GeriaSims and Care of the Aging Medical Patient
      (CHAMP) modules addressing issues in palliative and hospice medicine found in the
      Portal of Geriatric Online Education, a free on-line repository of geriatric
      educational materials for medical educators. GeriaSims is a self-directed
      teaching module designed to systematically address many of the important
      questions involved in caring for individuals with chronic progressive and life
      limiting illnesses. It is well suited for physicians, particularly medical
      residents and fellows in-training, who provide care for medically complicated
      elderly and terminally ill individuals. The CHAMP module is designed to
      familiarize physician educators with palliative and hospice medicine basics to
      teach residents and fellows through didactic slides, although it can probably be
      adapted for use by residents and fellows if audio commentary accompanies the
      slides. Both modules address practical approaches to addressing palliative care
      in patients and their families. They are useful teaching tools that address an
      important learning need and can be readily used to supplement current residency
      curriculum in hospice and palliative medicine.

PMID- 22642508
TI  - Age-based disparity in outcomes of intestinal transplants in pediatric patients.
AB  - Outcomes of intestinal transplants (ITx; n = 977) for pediatric patients are
      examined using the United Network for Organ Sharing data from 1987 to 2009.
      Recipients were divided into four age groups: (1) <2 years of age (n = 569), (2)
      2-6 years (n = 219), (3) 6-12 years (n = 121) and (4) 12-18 years (n = 68). Of
      977 ITx, 287 (29.4%) were isolated ITx and 690 (70.6%) were liver and ITx (L
      ITx). Patient survival for isolated ITx at 1, 3 and 5 years, 85.3%, 71.3% and
      65.0%, respectively, was significantly better than L-ITx, 68.4%, 57.0% and 51.4%,
      respectively, (p = 0.0001); this was true for all age groups, except for patients
      <2 years of age. The difference in graft survival between isolated ITx and L-ITx
      was significant at 1 and 3 years (Wilcoxon test, p = 0.0012). After attrition
      analysis of graft survival of patients who survived past first year, 3 and 5
      years, graft survival for L-ITx patient was significantly better than those for
      isolated ITx. Isolated ITx should be considered early before the onset of liver
      disease in children >2 with intestinal failure but is not advantageous in
      patients <2 years.

PMID- 22642509
TI  - Theoretical elucidation on the regio-, diastereo-, and enantio-selectivities of
      chiral primary-tertiary diamine catalyst for asymmetric direct aldol reactions of
      aliphatic ketones.
AB  - The asymmetric direct aldol reactions of aliphatic ketones (acetone, butanone,
      and cyclohexanone) with 4-nitrobenzaldehyde catalyzed by a chiral primary
      tertiary diamine catalyst (trans-N,N-dimethyl diaminocyclohexane) have been
      investigated by performing density functional theory calculations to rationalize
      the experimentally observed stereoselectivities. Focused on the crucial C-C bond
      forming steps, we located several low-lying transition states and predicted their
      relative stabilities. The calculated results demonstrate that the catalytic
      direct aldol reactions of acetone favors the (S)-enantiomer and that butanone
      prefers the branched syn-selective product, while cyclohexanone yields
      predominantly the opposite anti-selective product. The theoretical results are in
      good agreement with the experimental findings and provide a reasonable
      explanation for the high enantioselectivity and diastereoselectivity, as well as
      regioselectivity, of the aldol reactions under consideration.

PMID- 22642510
TI  - Evidence for a physical component to the radiation-induced bystander effect?
AB  - PURPOSE: The nature of the transferrable factor which goes from irradiated
      objects to bystander objects remains undefined. Most agree that a chemical entity
      is the likely 'factor' although some authors have produced in vitro evidence for
      the involvement of a physical component or a very potent volatile capable of
      traveling through air distances. In this paper we test the hypothesis that the
      communicated signal may be physical at least in part. METHODS: The in vivo fish
      model was used to allow signal production and response to occur in organisms in
      vivo without any shared blood or central nervous system (CNS) connections. A
      reporter assay and calcium flux measurements were used to detect signal
      production when irradiated fish were separated from unirradiated fish by (a) a
      plastic container, and (b) a foil-wrapped plastic container. RESULTS: The
      unirradiated fish showed bystander effects in both cases. The use of foil
      excludes the possibility of a light signal and although a highly active volatile
      could travel from one tank to another, the arrangement of sham and irradiated
      tanks makes it highly unlikely that this could explain our result. CONCLUSION: We
      conclude that there must be a physical component in the mechanism such as a weak
      acoustic or electromagnetic signal.

PMID- 22642511
TI  - Resiliently spherical micelles of alkyltrimethylammonium surfactants with
      multivalent, hydrolyzable counterions.
AB  - A series of C(12)-C(16) alkyltrimethylammonium surfactants with hydrolyzable
      phosphate (PO(4)(3-), HPO(4)(2-), and H(2)PO(4)(-)), oxalate (HC(2)O(4)(-) and
      C(2)O(4)(2-)), and carbonate (HCO(3)(-) and CO(3)(2-)) counterions have been
      prepared, and their micellar solution behavior has been characterized. Critical
      micelle concentrations were measured using electrical conductivity and were found
      to depend on both the counterion and its hydrolysis state. All monovalent
      counterions bind less strongly to the micelle surface than does bromide or
      chloride, whereas multivalent species bind more strongly. Small-angle neutron
      scattering reveals that, unlike alkyltrimethylammonium bromides and chlorides,
      micelles are small and spherical in the presence of hydrolyzable counterions of
      all valences and remain spherical even in the presence of added electrolyte. This
      is consistent with the strong solvation of even strongly bound hydrolyzable
      counterions, which prevents the screening of repulsions between adjacent
      headgroups necessary for sphere-cylinder transformations. Salts of multivalent
      hydrolyzable counterions could thus be used to control the micelle structure in
      novel ways.

PMID- 22642512
TI  - Interleukin-2 receptor targeted therapy of ocular disease of HTLV-1-associated
      adult T-cell leukemia.
AB  - PURPOSE: To report two cases of patients with ocular manifestations of human T
      cell lymphotropic virus type-1 (HTLV-1) associated adult T-cell leukemia/lymphoma
      (ATL) who were successfully treated with interleukin-2 receptor targeted
      therapies. METHOD: Case series. RESULTS: Two patients with HTLV-1-associated ATL
      developed symptomatic scleritis. In the first case, conjunctival biopsy showed
      leukemic infiltration that was confirmed by T-cell receptor polymerase chain
      reaction (PCR) demonstrating a clonal rearrangement. As treatment for ATL, both
      cases received interleukin-2 receptor targeted therapy. In one patient,
      daclizumab, a monoclonal antibody directed against the alpha chain of the
      interleukin-2 (IL-2) receptor, was used. The second patient was treated with
      denileukin diftitox, an immunotoxin fusion protein that targets the IL-2
      receptor. Improvement in scleritis was noted in both patients. CONCLUSION:
      Scleritis in patients with underlying HTLV-1-associated ATL is responsive to IL-2
      receptor targeted therapies.

PMID- 22642513
TI  - Pulsed delivery of inhaled nitric oxide counteracts hypoxaemia during 2.5 hours
      of inhalation anaesthesia in dorsally recumbent horses.
AB  - OBJECTIVE: The study aimed to investigate the effect of varying pulse lengths of
      inhaled nitric oxide (iNO), and 2.5 hours of continuous pulse-delivered iNO on
      pulmonary gas exchange in anaesthetized horses. STUDY DESIGN: Experimental study.
      ANIMALS: Six Standardbred horses. METHODS: Horses received acepromazine,
      detomidine, guaifenesin, thiopentone and isoflurane in oxygen, were positioned in
      dorsal recumbency and were breathing spontaneously. iNO was on average pulsed
      during the first 20, 30, 43 or 73% of the inspiration in 15 minute steps. The
      pulse length that corresponded to the highest (peak) partial pressure of arterial
      oxygen (PaO(2) ) in the individual horses was determined and delivered for a
      further 1.5 hours. Data measured or calculated included arterial and mixed venous
      partial pressures of O(2) and CO(2) , heart rate, respiratory rate, expired
      minute ventilation, pulmonary and systemic arterial mean pressures, cardiac
      output and venous admixture. Data (mean +/- SD) was analysed using anova with p <
      0.05 considered significant. RESULTS: Although the pulse length of iNO that
      corresponded to peak PaO(2) varied between horses, administration of all pulse
      lengths of iNO increased PaO(2) compared to baseline. The shortest pulse lengths
      that resulted in the peak PaO(2) were 30 and 43% of the inspiration.
      Administration of iNO increased PaO(2) (12.6 +/- 4.1 kPa [95 +/- 31 mmHg] at
      baseline to a range of 23.0 +/- 8.4 to 25.3 +/- 9.0 kPa [173 to 190 mmHg]) and
      PaCO(2) (8.5 +/- 1.2 kPa [64 +/- 9 mmHg] to 9.8 +/- 1.5 kPa [73 +/- 11 mmHg]) and
      decreased venous admixture from 32 +/- 6% to 25 +/- 6%. The increase in PaO(2)
      and decrease in venous admixture was sustained for the entire 2.5 hours of iNO
      delivery. CONCLUSIONS: The improvement in arterial oxygenation during pulsed
      delivery of iNO was significant and sustained throughout 2.5 hours of
      anaesthesia. CLINICAL RELEVANCE: Pulsed iNO potentially could be used clinically
      to counteract hypoxemia in anaesthetized horses.

PMID- 22642514
TI  - Similar symptom patterns in gastroesophageal reflux patients with and without
      hiatal hernia.
AB  - Gastroesophageal reflux disease is a common clinical entity in Western societies.
      Its association with hiatal hernia has been well documented; however, the
      comparative clinical profile of patients in the presence or absence of hiatal
      hernia remains mostly unknown. The aim of the present study was to delineate and
      compare symptom, impedance, and manometric patterns of patients with and without
      hiatal hernia. A cumulative number of 120 patients with reflux disease were
      enrolled in the study. Quality of life score, demographic, symptom, manometric,
      and impedance data were prospectively collected. Data comparison was undertaken
      between patients with and without hiatal hernia. A P-value < 0.05 was considered
      statistically significant. Patients with hiatal hernia tended to be older than
      patients without hernia (52.3 vs. 48.6 years, P < 0.05), whereas quality of life
      scores were slightly better for the former (97.0 vs. 88.2, P= 0.005).
      Regurgitation occurred more frequently in patients without hiatal hernia (78.3%
      vs. 93.9%, P < 0.05). Otherwise, no differences were found with regard to
      esophageal and extraesophageal symptoms. However, lower esophageal sphincter
      pressures (7.7 vs. 10.0 mmHg, P= 0.007) and more frequent reflux episodes
      (upright, 170 vs. 134, P= 0.01; supine, 41 vs. 24, P < 0.03) were documented for
      patients with hiatal hernia on manometric and impedance studies. Distinct
      functional characteristics in patients with and without hiatal hernia may suggest
      a tailored therapeutic management for these diverse patient groups. 

PMID- 22642515
TI  - Bridging the gap between clinical research and clinical practice: introduction to
      the special section.
AB  - This Special Section, developed by the American Psychology Association's Division
      12 (Clinical) 2011 Committee on Science and Practice, highlights different ideas
      to help bridge the gap between clinical research and clinical practice, and notes
      recent innovations that help make research-practice integration feasible. The
      articles consider how to break down the barriers to enhance researcher
      practitioner dialogue, as well as how to make ongoing outcome assessment feasible
      for clinicians. Moreover, the articles address how to promote training in
      evidence-based practice, and how to translate efficacy research into clinical
      practice and clinical insight into empirical study to better establish a two-way
      bridge between research and practice. Ultimately, we hope this series can speak
      to many different types of psychologists, whether they work mainly as researchers
      or practitioners, so they can see new ways to integrate and learn from both
      research and practice.

PMID- 22642516
TI  - Healing the research-practice split: let's start with me.
AB  - This article highlights many of the major issues that separate the researcher
      from the clinician and then suggests some possible solutions. The format involves
      an enacted two-chair dialogue between my researcher side and my therapist side.
      The dialogue involves three phases. Phase 1 involves each side presenting a straw
      man of the other's position. In Phase 2, the two sides engage in a creative
      dialogue regarding many of the issues that divide them. Phase 3 eventuates in a
      series of synthetic solutions that honors the concerns and core values of each
      side. The solutions include: (a) broadening the definition of clinically useful
      research, (b) researcher-practitioner collaboration, (c) appropriate
      dissemination of user-friendly research findings, (d) translating research
      findings into experience-near procedures such as the systematic case studies, and
      (e) providing clinicians with easy access to a video archive of research
      therapies.

PMID- 22642518
TI  - Helping clinicians to use and learn from research-based systems: the OQ-analyst.
AB  - Evidence is presented that suggests routine clinical practice is limited by
      therapist optimism about their personal effects on patients. This optimistic view
      prevents them from recognizing which of their patients are headed for a negative
      treatment outcome and taking steps to prevent poor outcomes for such cases. A
      formal method of measuring and monitoring patient treatment response that
      includes prediction of treatment failure is presented along with evidence that it
      more than doubles positive outcomes while substantially reducing deterioration.
      In addition, the collection of archival data helps therapists answer questions of
      interest to them, such as their own degree of effectiveness, and outcomes with
      minority clients, genders, and related clinical issues.

PMID- 22642519
TI  - The treatment outcome package: facilitating practice and clinically relevant
      research.
AB  - As an effort to foster the use of standardized data in clinical practice, this
      article discusses an outcome measure developed by clinicians for use in
      naturalistic settings: the treatment outcome package (TOP). In addition to
      describing how the TOP can be used in day-to-day practice, the article
      illustrates how its multidimensional structure can inform several aspects of
      clinical work, such as the development of case formulations, facilitation of
      client-therapist communication, tracking (positive and negative) change during
      treatment, and the documentation of specific area of therapist expertise. This
      article recognizes the challenges and drawbacks that are associated with the use
      of a standardized outcome measure and also describes three ways by which the TOP
      can contribute to the strengthening of the relationship between research and
      practice.

PMID- 22642520
TI  - An opportunity to bridge the gap between clinical research and clinical practice:
      implications for clinical training.
AB  - Clinical researchers and clinical practitioners share a goal of increasing the
      integration of research and clinical practice, which is reflected in an evidence
      based practice (EBP) approach to psychology. The EBP framework involves the
      integration of research findings with clinical expertise and client
      characteristics, values, and preferences, and consequently provides an important
      foundation for conducting clinically relevant research, as well as empirically
      based and clinically sensitive practice. Given the critical role that early
      training can play in the integration of science and practice and in promoting the
      future of the field, the present article addresses predoctoral training programs
      as a context for adopting an EBP approach to clinical work. We address training
      in the three components of EBP and provide suggestions for curriculum development
      and practicum training that we hope will contribute to bridging the gap between
      research and practice.

PMID- 22642521
TI  - Adaptations to the coping power program's structure, delivery settings, and
      clinician training.
AB  - This article describes the conceptual framework for the Coping Power program that
      has focused on proximal risk factors that can actively alter preadolescent
      children's aggressive behavior. The results of initial controlled efficacy trials
      are summarized. However, consistent with the theme of this special section, some
      clinicians and workshop participants have indicated barriers to the
      implementation of the Coping Power program in their service settings. In response
      to these types of concerns, three key areas of programmatic adaptation of the
      program that serve to address these concerns are then described in the article.
      First, existing and in-process studies of variations in how the program can be
      delivered are presented. Existing findings indicate how the child component fares
      when delivered by itself without the parent component, how simple monthly
      boosters affect intervention effects, and whether the program can be reduced by a
      third of its length and still be effective. Research planned or in progress on
      program variations examines whether group versus individual delivery of the
      program affects outcomes, whether the program can be adapted for early
      adolescents, whether the program can be delivered in an adaptive manner with the
      use of the Family Check Up, and whether a brief, efficient version of the program
      in conjunction with Internet programming can be developed and be effective.
      Second, the program has been and is being developed for use in different
      settings, other than the school-based delivery in the efficacy trials. Research
      has examined its use with aggressive deaf youth in a residential setting, with
      Oppositional Defiant Disorder and Conduct Disorder children in outpatient
      clinics, and in after-school programs. Third, the article reports how variations
      in training clinicians affect their ability to effectively use the program.

PMID- 22642523
TI  - Integrated cognitive-behavioral and psychodynamic psychotherapy for intimate
      partner violent men.
AB  - Intimate partner violence (IPV) continue to have widespread negative effects on
      victims, children who witness IPV, and perpetrators. Current treatments have
      proven to be only marginally effective in stopping or reducing IPV by men. The
      two most prominent treatment approaches are feminist sociocultural and cognitive
      behavioral therapy (CBT). The feminist sociocultural approach has been criticized
      for failing to adequately consider the therapeutic alliance, personality factors,
      and sole focus on patriarchy as the cause for IPV, whereas CBT has been
      criticized for failing to attend to motivation issues in treatment protocols.
      This article reviews the effectiveness of current treatments for partner-violent
      men, examines relationship and personality variables related to IPV and its
      treatment, and presents an emerging IPV treatment model that combines CBT and
      psychodynamic therapy. The article addresses how psychodynamic therapy is
      integrated into the more content-based elements of CBT.

PMID- 22642522
TI  - A translational model of research-practice integration.
AB  - We propose a four-level, recursive Research-Practice Integration framework as a
      heuristic to (a) integrate and reflect on the articles in this Special Section as
      contributing to a bidirectional bridge between research and practice, and (b)
      consider additional opportunities to address the research-practice gap. Level 1
      addresses Treatment Validation studies and includes an article by Lochman and
      colleagues concerning the programmatic adaptation, implementation, and
      dissemination of the empirically supported Coping Power treatment program for
      youth aggression. Level 2 translation, Training in Evidence-Based Practice,
      includes a paper by Hershenberg, Drabick, and Vivian, which focuses on the
      critical role that predoctoral training plays in bridging the research-practice
      gap. Level 3 addresses the Assessment of Clinical Utility and Feedback to
      Research aspects of translation. The articles by Lambert and Youn, Kraus, and
      Castonguay illustrate the use of commercial outcome packages that enable
      psychotherapists to integrate ongoing client assessment, thus enhancing the
      effectiveness of treatment implementation and providing data that can be fed back
      to researchers. Lastly, Level 4 translation, the Cross-Level Integrative Research
      and Communication, concerns research efforts that integrate data from clinical
      practice and all other levels of translation, as well as communication efforts
      among all stakeholders, such as researchers, psychotherapists, and clients. Using
      a two-chair technique as a framework for his discussion, Wolfe's article depicts
      the struggle inherent in research-practice integration efforts and proposes a
      rapprochement that highlights advancements in the field.

PMID- 22642524
TI  - Predictors of child-therapist alliance in cognitive-behavioral treatment of
      children referred for oppositional and antisocial behavior.
AB  - We examined the therapeutic alliance in evidence-based treatment for children
      (N=97, 24 girls and 73 boys, ages 6-13 years) referred clinically for
      oppositional, aggressive, and antisocial behavior. We predicted that the quality
      of the child-therapist alliance would be related to therapeutic improvements in
      the children at the end of treatment and that the alliance would be predicted by
      alliance-relevant child characteristics (intellectual and social competencies)
      assessed before treatment. Multiple perspectives were obtained to evaluate child
      characteristics before treatment, alliance during the course of treatment, and
      therapeutic change at the end of treatment. The main findings were as follows:
      (1) the child-therapist alliance was related to therapeutic change at the end of
      treatment. The better the quality of the therapeutic alliance during treatment,
      the greater the therapeutic change among the children; (2) intellectual and
      social competencies of the child before treatment predicted the quality of the
      therapeutic alliance. Children higher in intellectual and social competencies
      formed a better child-therapist alliance; and (3) intellectual and social
      competencies did not account for or explain the connection of alliance and
      therapeutic change. The findings could not easily be attributed to the influence
      of other domains (socioeconomic disadvantage, parent psychopathology and stress,
      and severity and scope of child dysfunction) that plausibly might contribute to
      alliance and therapeutic change or to rater effects (common rater variance) among
      predictors and outcome criteria. We propose that the next steps for child
      alliance research is to better describe factors that contribute to alliance and
      to explain precisely what mechanisms might be involved that connect alliance
      during treatment with changes in individual functioning.

PMID- 22642525
TI  - Interpersonal predictors of early therapeutic alliance in a transdiagnostic
      cognitive-behavioral treatment for adolescents with anxiety and depression.
AB  - The importance of therapeutic alliance in predicting treatment success is well
      established, but less is known about client characteristics that predict
      alliance. This study examined alliance predictors in adolescents with anxiety
      and/or depressive disorders (n=31) who received a transdiagnostic cognitive
      behavioral treatment, the Unified Protocol for the Treatment of Emotional
      Disorders in Youth (Ehrenreich, Buzzella, Trosper, Bennett, & Barlow, 2008) in
      the context of a larger randomized controlled trial. Alliance was assessed at
      session three by therapists, clients, and independent observers. Results
      indicated that alliance ratings across the three informant perspectives were
      significantly associated with one another, but that pretreatment interpersonal
      variables (e.g., social support, attachment security, and social functioning in
      current family and peer relationships) were differentially associated with
      varying informant perspectives. Adolescent and observer ratings of alliance were
      both predicted by adolescent self-reports on measures reflecting how they
      perceive their interpersonal relationships. In addition, adolescent-reported
      symptom severity at pretreatment predicted observer ratings of alliance such that
      adolescents who indicated greater anxiety and depressive symptoms were rated as
      having stronger early alliances by independent observers. Therapists perceived
      having weaker early alliances with adolescents evidencing clinically significant
      depression at intake as compared with adolescents diagnosed with anxiety
      disorders alone. Future research is needed to examine whether identification of
      relevant interpersonal factors at intake can help improve initial therapeutic
      engagement and resulting outcomes for the psychosocial treatment of adolescents
      with anxiety and depressive disorders.

PMID- 22642526
TI  - Weekly therapist ratings of the therapeutic relationship and patient introject
      during the course of dialectical behavioral therapy for the treatment of
      borderline personality disorder.
AB  - The purpose of the present study was to examine theory-driven hypotheses of the
      therapeutic relationship and patient introject in dialectical behavior therapy
      (DBT; Linehan, 1993) for the treatment of borderline personality disorder. A
      total of 14 DBT therapists provided weekly ratings of the therapeutic
      relationship and patient introject (N=41) during the course of a randomized
      controlled trial of DBT for the treatment of borderline personality disorder.
      Using hierarchical linear modeling (Raudenbush & Bryk, 2002), we tested four
      hypotheses of the therapeutic relationship as predicted by DBT and behavioral
      theory. Results supported three of our four predicted hypotheses of the
      therapeutic relationship, including the effective use of balancing autonomy and
      control in the therapeutic relationship, the importance of therapists'
      maintaining a nonpejorative stance toward the patient, and the use of therapist
      warmth and autonomy as a contingency for improved intrapsychic outcome. Results
      did not support a modeling hypothesis of the therapeutic relationship. The study
      supported a DBT and behavioral model of the therapeutic relationship from the
      perspective of the treating clinician.

PMID- 22642527
TI  - Effectiveness of combined individual and group dialectical behavior therapy
      compared to only individual dialectical behavior therapy: a preliminary study.
AB  - Dialectical behavior therapy (DBT) is an effective therapy. However, treating
      borderline personality disorder (BPD) patients with standard DBT can be
      problematic in some institutions due to logistical or cost limitations. The aim
      of this preliminary study is to examine the efficacy of Individual DBT in 37 BPD
      patients, compared with Combined individual/Group DBT in 14 BPD patients. Outcome
      measures included suicide attempts, self-harm behaviors, and visits to emergency
      departments. These variables were examined at pretreatment, 12 months/end of
      treatment, and at an 18-month follow-up. In addition, dropout rates were
      examined. Significant improvements on the outcome measures were observed across
      both versions of DBT treatment, particularly at the 18-month follow-up
      assessment. No significant differences were observed between Individual DBT and
      Combined individual/Group DBT on any of the posttreatment evaluations. An
      individual version of DBT may be an effective and less costly option for BPD
      treatment. Larger controlled trials are needed to confirm the results.

PMID- 22642528
TI  - Cognitive behavioral therapy for psychosis in clinical practice.
AB  - Across two continents, Cognitive-Behavioral Therapy for Psychosis (CBT-P) has
      been endorsed as an adjunctive treatment for individuals who experience
      persistent positive symptoms of schizophrenia. The moderate effect sizes reported
      in early studies and reviews were followed by better controlled studies
      indicating more limited effect sizes. This article provides a review of the
      literature that addresses the effectiveness of CBT-P, including particular areas
      of emphasis and practice elements associated with this approach. In addition,
      because the majority of research on CBT-P has been performed in the United
      Kingdom, implications for implementation and sustainability of this practice in
      the United States are presented.

PMID- 22642531
TI  - The molecular design of S-nitrosothiols as photodynamic agents for controlled
      nitric oxide release.
AB  - Nitric oxide is a small messenger molecule utilized by nature in cell signalling
      and the non-specific immune response. At present, nitric oxide releasing prodrugs
      cannot be efficiently targeted towards a specific body compartment, which
      restricts their therapeutic applications. To address this limitation, we have
      designed two photolabile nitric oxide releasing prodrugs, tert-butyl S
      nitrosothiol and tert-dodecane S-nitrosothiol, which are based on the S
      nitrosothiol functionality. By modulating the prodrugs' hydrophobicity, we
      postulated that we could increase their stability within the cell by preventing
      their interaction with hydrophilic thiols and metal ions; processes that are
      known to inactivate this prodrug class. Our data demonstrate that these prodrugs
      have improved nitric oxide release kinetics compared to currently available S
      nitrosothiols, as they are highly stable in vitro in the absence of irradiation
      (t(1/2) > 3 h), while their rate of decomposition can be regulated by controlling
      the intensity or duration of the photostimulus. Nitric oxide release can readily
      be achieved using non-laser based light sources, which enabled us to characterize
      photoactivation as a trigger mechanism for nitric oxide release in A549 lung
      carcinoma cells. Here we confirmed that irradiation induced highly significant
      increases in cytotoxicity within a therapeutic drug range (1-100 MUm), and the
      utility of this photoactivation switch opens up avenues for exploring the
      applications of these prodrugs for chemical biology studies and chemotherapy.

PMID- 22642532
TI  - Ankle muscle activation in people with haemophilia.
AB  - Since normative surface EMG (SEMG) values for muscles acting at the knee joint
      are available for people with haemophilia, increasing interest is noticeable for
      other joints affected by haemophilic arthropathy. Adequate activity of shank
      muscles is an important key for appropriate postural control. The aim of this
      study was to determine differences in muscle activation patterns of lower leg
      muscles between people with and without haemophilia during upright standing. SEMG
      of tibialis anterior (TA), fibularis longus (FL), lateral (LG) and medial (MG)
      heads of gastrocnemius, and soleus (SO) muscles of both sides were recorded in 25
      haemophilic patients (H) and 25 non-haemophilic control subjects (C) while
      standing on even ground. The Gilbert-Score was used to assign sides to major (H
      MA) and minor (H-MI) affected ankle joints in H. To normalize the SEMG
      amplitudes, amplitude ratios (percentage of cumulated activity) were calculated.
      Compared to controls, TA ratios showed higher and MG reduced levels in both H
      groups (P < 0.01). In the H-MA subgroup of H, FL also joined the TA behaviour
      whereas SO had similar activation direction as MG. Although possible descending
      influences from the knee joints cannot be excluded, this can be interpreted as a
      compensational mechanism due to the severity of the orthopaedic status of the
      ankle, which with increasing heaviness is accompanied by reduced plantar flexion
      capability. However, ankle joint integrity appears to be reduced in H, with TA
      and MG seeming to play key roles for neuromuscular control of upright posture.

PMID- 22642533
TI  - Direct medical costs associated with atopic diseases among young children in
      Thailand.
AB  - OBJECTIVE: Allergic diseases are the most common childhood illness in Thailand.
      Their prevalence has been rising over time, with several studies having revealed
      substantial economic burden. However, no such study had yet been conducted for
      Thailand. The aim of this study was to estimate direct medical costs associated
      with atopic diseases among children aged 0-5 years in Thailand. RESEARCH DESIGN
      AND METHODS: A cost-of-illness model was constructed to estimate the total direct
      medical costs of atopic diseases comprising atopic dermatitis, chronic rhinitis,
      asthma (i.e., recurrent wheeze), and cow's milk allergy. The model employed a
      prevalence-based approach, considering a total number of atopic cases in 2010.
      Direct medical costs were estimated using a bottom-up analysis with the
      estimation of the quantity of healthcare resource use and the unit costs.
      Epidemiological data were obtained from literature and Thai surveys, whereas
      treatment unit costs were from either a hospital database or Thai standard cost
      list. Expert opinion informed type, frequency, and quantity of medical resources
      utilized. Key limitations included lack of data-driven evidences on severity
      distribution for this particular age group, indirect costs, and medical resource
      use associated with each condition. RESULTS: Total direct cost was estimated to
      be THB 27.8 billion (US$899 million). Treatments contributed largest to the total
      costs (46%), followed by inpatient care (37%), outpatient care (12%), and
      monitoring and labs (5%). Costs per treated patient were highest in cow's milk
      allergy (THB 64,383; US$2077), followed by rhinitis (THB 12,669; US$409), asthma
      (THB 9633; US$312), and atopic dermatitis (THB 5432; US$175). CONCLUSION: Atopic
      diseases in young children are associated with substantial burden in direct
      medical costs to Thailand. These costs can be diminished through nutritional
      intervention recognized to effectively decrease the incidence of atopic diseases.

PMID- 22642534
TI  - Nocturnal hypokinesia and sleep quality in Parkinson's disease.
AB  - OBJECTIVES: To study the relationship between nocturnal hypokinesia and sleep
      quality in Parkinson's disease (PD). DESIGN: Questionnaire study using intergroup
      analysis. SETTING: Parkinson Centre Nijmegen, a tertiary university referral
      center. PARTICIPANTS: Two hundred forty individuals with Parkinson's disease.
      MEASUREMENTS: Clinical and demographic data were obtained. Nocturnal hypokinesia
      was assessed using Question 35 of the Parkinson's Disease Quality of Life
      Questionnaire and rated on a 5-point Likert scale (1 = all of the time to 5 =
      never). The Pittsburgh Sleep Quality Index (PSQI) was used to quantify sleep
      quality, higher scores indicating poorer sleep quality. RESULTS: One hundred
      thirty-five of 240 participants had difficulties turning over in bed. Mean PSQI
      scores were significantly higher in participants with nocturnal hypokinesia (7.7
      +/- 4.1) than in those without (6.1 +/- 3.4, P = .001). A regression model
      correcting for age, disease duration, and Hoehn and Yahr stage showed a
      significant influence of nocturnal hypokinesia on sleep quality (coefficient of
      determination = 0.042, standardized-beta = 0.163, P = .03). There was a linear
      relationship between frequency of nocturnal hypokinesia and sleep quality.
      CONCLUSION: This is the first study that documents that nocturnal hypokinesia
      negatively affects sleep quality in PD. Nocturnal hypokinesia therefore merits
      therapeutic attention, including optimal nighttime dopaminergic treatment and
      education about turning strategies in bed.

PMID- 22642536
TI  - T cell autoreactivity in the transplant milieu.
AB  - Autoreactive T cell responses in autoimmune disease are directed to tissue
      antigens but differ from allospecific T cells in several important respects,
      reflecting the circumstances of their selection, activation and expansion in
      vivo. Both genetic and acquired traits conspire to generate autoreactive effector
      cells that are refractory to normal control mechanisms, resulting in persistent
      and deleterious immunity to tissue antigens. When these same tissue antigens are
      reintroduced into an autoimmune setting, such as with pancreas or islet
      transplantation into a type 1 diabetic individual, the potential for recurrent
      activation of the underlying effector memory response presents a therapeutic
      challenge.

PMID- 22642537
TI  - New beverages of lemon juice enriched with the exotic berries maqui, acai, and
      blackthorn: bioactive components and in vitro biological properties.
AB  - Following previous research on lemon juice enriched with berries, the aim of this
      work was to design new blends based on lemon juice mixed with different edible
      berries of exotic and national origin: maqui ( Aristotelia chilensis  (Molina)
      Stuntz), acai ( Euterpe oleracea  Mart.), and blackthorn ( Prunus spinosa  L.).
      The phytochemical characterization of controls and blends was performed by HPLC
      DAD-ESI/MS(n). Their antioxidant capacity against DPPH, superoxide, and hydroxyl
      radicals and hypochlorous acid and their potential to inhibit cholinesterases
      were also assessed. The profiling of the red fruits and lemon revealed a wide
      range of bioactive phenolics. The novel beverage based on lemon juice and maqui
      berry (LM) was the most interesting blend in terms of antioxidant capacity. Berry
      control samples displayed reduced effects on acetylcholinesterase and
      butyrylcholinesterase, the lemon juice control being always the most active. This
      activity was also remarkable for lemon-blackthorn (LB) and lemon-acai (LA)
      blends, the last being the most effective inhibitor of cholinesterases among all
      samples. The results suggested that lemon juice enriched with berries could be of
      potential interest in the design of new drinks with a nutritive related function
      on health for chronic diseases.

PMID- 22642538
TI  - Cationic porphyrins are reversible proteasome inhibitors.
AB  - The aim of this study is to verify if water-soluble porphyrins can be used as
      proteasome inhibitors. We have found that cationic porphyrins inhibit proteasome
      peptidase activities much more effectively than the corresponding anionic
      derivatives. The relevance of electrostatics in driving porphyin-proteasome
      interactions has been confirmed by the observation that the inhibitory efficiency
      of the cationic macrocycles decreases with the number of positive substituents.
      We have also investigated various metalloporphyrins, which differ due to the
      different propension of the central metal ion toward axial coordination. Our
      experimental results indicate that the naked cationic porphyrins are the most
      active in reversibly inhibiting the three main protease activities of the
      proteasome in the micromolar range. A spectroscopic characterization of porphyrin
      proteasome interactions by UV-vis spectra parallels the results of inhibition
      assays: the higher the inhibitory effect the stronger the spectroscopic
      variations are. To interpret the action of porphyrins at a molecular level, we
      have performed calculations evidencing that cationic porphyrins may hinder the
      access to the canonical proteolytic site on the proteasome beta5 subunit. In
      particular, an inspection of the top-scoring docking modes shows that the
      tetracationic porphyrin blocks the catalytic pocket, close to the N termini of
      the beta5 proteasome subunit, more efficiently than its anionic counterpart.
      Proteasome inhibition activity of porphyrins unites their known anticancer
      properties making them suitable as a scaffold for the design of novel
      multitargeted molecules.

PMID- 22642539
TI  - Development of ultra-high erucic acid oil in the industrial oil crop Crambe
      abyssinica.
AB  - Erucic acid (22 : 1) is a major feedstock for the oleochemical industry. In this
      study, a gene stacking strategy was employed to develop transgenic Crambe
      abyssinica lines with increased 22 : 1 levels. Through integration of the
      LdLPAAT, BnFAE1 and CaFAD2-RNAi genes into the crambe genome, confirmed by
      Southern blot and qRT-PCR, the average levels of 18 : 1, 18 : 2 and 18 : 3 were
      markedly decreased and that of 22 : 1 was increased from 60% in the wild type to
      73% in the best transgenic line of T4 generation. In single seeds of the same
      line, the 22 : 1 level could reach 76.9%, an increase of 28.0% over the wild
      type. The trierucin amount was positively correlated to 22 : 1 in the transgenic
      lines. Unlike high erucic rapeseed, the wild-type crambe contains 22 : 1 in the
      seed phosphatidylcholine and in the sn-2 position of triacylglycerols (5% and 8%,
      respectively). The transgenic line with high 22 : 1 had decreased 22 : 1 level in
      phosphatidylcholine, and this was negatively correlated with the 22 : 1 level at
      the sn-2 position of TAG. The significances of this study include (i) achieving
      an unprecedented level of 22 : 1 in an oil crop; (ii) disclosing mechanisms in
      the channelling of a triacylglycerol-specific unusual fatty acid in oil seeds;
      (iii) indicating potential limiting factors involved in the erucic acid
      biosynthesis and paving the way for further increase of this acid and (iv)
      development of an added value genetically modified oil crop having no risk of
      gene flow into feed and food crops.

PMID- 22642540
TI  - Improved catalytic performance of lipase accommodated in the mesoporous silicas
      with polymer-modified microenvironment.
AB  - The highly ordered mesoporous silicas with elaborately controlled
      microenvironment were synthesized via covalent incorporation of long-chain
      polymers (M(w) = 2000 g mol(-1)) bearing specific hydrophilic/hydrophobic
      balance. The microenvironment (hydrophilicity/hydrophobicity) of the mesoporous
      silicas was quantitatively determined by gas adsorption experiments and
      investigated by lysozyme (LYZ) adsorption. The relative activity of lipase from
      Pseudomonas cepacia (PCL) encapsulated in the mesoporous silica with moderate
      hydrophobic microenvironment (hereafter denoted as MHM) reaches up to 281%
      compared with the free PCL, notably higher than that of PCL accommodated in the
      mesoporous silicas with hydrophilic or strong hydrophobic microenvironment (20.7
      26.2% relative to the free PCL). Moreover, PCL entrapped in the nanochannels with
      MHM affords the highest initial rate in the kinetic resolution of (R,S)-1
      phenylethanol relative to other immobilized PCL. The above results suggest that
      the MHM could render the active center of PCL entirely exposed to the substrates
      without interrupting its native conformation in the "interfacial activation". In
      addition, the nanochannels with MHM could markedly improve the thermal stability
      of PCL (preserving nearly 60% of the initial activity after the incubation at 70 
      degrees C for 2 h) and facilitate the recycling of the immobilized PCL in both
      aqueous and organic media. Our work demonstrates that the subtle modulation of
      the microenvironment of mesoporous silicas for enzyme immobilization designates a
      very promising strategy to fabricate the highly active and stable heterogeneous
      biocatalysts for industrial application.

PMID- 22642541
TI  - Discovery, synthesis and evaluation of novel cholesterol absorption inhibitors.
AB  - Chemical-based common feature pharmacophore modelling of Niemann Pick C1 Like 1
      inhibitors was performed to provide some insights on the important pharmacophore
      features essential for Niemann Pick C1 Like 1 inhibition using Discovery Studio
      V2.5. After in-house database screening, a new series of substituted
      oxazolidinones, selected from the top ranked hits, have been synthesized and
      evaluated as novel cholesterol absorption inhibitors. All compounds demonstrated
      effect of different degrees in lowering the total cholesterol in serum,
      especially compounds 1a, 2a and 2d, the potency of which was comparable to that
      of ezetimibe. It was also found that 1a, 1d and 2d could raise high-density
      lipoprotein cholesterol levels markedly. Interestingly, compounds 2a-2f appeared
      to have the moderate potential to lower triglyceride levels, which were superior
      to that of normal cholesterol absorption inhibitors including ezetimibe.

PMID- 22642542
TI  - Population burden of long-term survivorship after severe sepsis in older
      Americans.
AB  - OBJECTIVES: To ascertain the absolute number of Medicare beneficiaries surviving
      at least 3 years after severe sepsis and to estimate their burden of cognitive
      dysfunction and disability. DESIGN: Retrospective cohort analysis of Medicare
      data. SETTING: All short-stay inpatient hospitals in the United States, 1996 to
      2008. PARTICIPANTS: Individuals aged 65 and older. MEASUREMENTS: Severe sepsis
      was detected using a standard administrative definition. Case-fatality,
      prevalence, and incidence rates were calculated. RESULTS: Six hundred thirty
      seven thousand eight hundred sixty-seven Medicare beneficiaries were alive at the
      end of 2008 who had survived severe sepsis 3 or more years earlier. An estimated
      476,862 (95% confidence interval (CI) = 455,026-498,698) had functional
      disability, with 106,311 (95% CI = 79,692-133,930) survivors having moderate to
      severe cognitive impairment. The annual number of new 3-year survivors after
      severe sepsis rose 119% during 1998 to 2008. The increase in survivorship
      resulted from more new diagnoses of severe sepsis rather than a change in case
      fatality rates; severe sepsis rates rose from 13.0 per 1,000 Medicare beneficiary
      years to 25.8 (P < .001), whereas 3-year case fatality rates changed much less,
      from 73.5% to 71.3% (P < .001) for the same cohort. Increasing rates of organ
      dysfunction in hospitalized individuals drove the increase in severe sepsis
      incidence, with an additional small contribution from population aging.
      CONCLUSIONS: Sepsis survivorship, which has substantial long-term morbidity, is a
      common and rapidly growing public health problem for older Americans. There has
      been little change in long-term case-fatality, despite changes in practice.
      Clinicians should anticipate more-frequent sequelae of severe sepsis in their
      patient populations.

PMID- 22642543
TI  - Recent patents regarding essential oils and the significance of their
      constituents in human health and treatment.
AB  - Essential oils derived from aromatic plants possess useful properties concerning
      human health, such as antibacterial, antiviral and antifungal activities. They
      can be used as natural alternatives to synthetic preparations to prevent and
      treat infectious diseases caused by multidrug resistant microorganisms. They are
      used successfully to treat respiratory tract, digestive system and skin
      infections. Many of them may be applied in anticancer therapy, cardiovascular and
      nervous system disorders, as well as to reduce the level of cholesterol and
      decrease and regulate the glucose level. Due to their ability to stimulate
      adrenal and estrogen hormone production and their antimicrobial properties, they
      are useful in the treatment of gynecological diseases. Oils are commonly used in
      the food and cosmetic industry. The present paper describes recent patents
      concerning potential uses of essential oils in human health and treatment of
      diseases.

PMID- 22642544
TI  - Localization of mesenchymal stromal cells dictates their immune or
      proinflammatory effects in kidney transplantation.
AB  - Multipotent mesenchymal stromal cells (MSC) have recently emerged as promising
      candidates for cell-based immunotherapy in solid-organ transplantation. However,
      optimal conditions and settings for fully harnessing MSC tolerogenic properties
      need to be defined. We recently reported that autologous MSC given posttransplant
      in kidney transplant patients was associated with transient renal insufficiency
      associated with intragraft recruitment of neutrophils and complement C3
      deposition. Here, we moved back to a murine kidney transplant model with the aim
      to define the best timing of MSC infusion capable of promoting immune tolerance
      without negative effects on early graft function. We also investigated the
      mechanisms of the immunomodulatory and/or proinflammatory activities of MSC
      according to whether cells were given before or after transplant. Posttransplant
      MSC infusion in mice caused premature graft dysfunction and failed to prolong
      graft survival. In this setting, infused MSC localized mainly into the graft and
      associated with neutrophils and complement C3 deposition. By contrast,
      pretransplant MSC infusion induced a significant prolongation of kidney graft
      survival by a Treg-dependent mechanism. MSC-infused pretransplant localized into
      lymphoid organs where they promoted early expansion of Tregs. Thus, pretransplant
      MSC infusion may be a useful approach to fully exploit their immunomodulatory
      properties in kidney transplantation.

PMID- 22642545
TI  - Flavor characteristics of seven grades of black tea produced in Turkey.
AB  - Seven grades of black tea [high-quality black tea (grades 1-3) and low-quality
      black tea (grades 4-7)], processed by CAYKUR Tea Processing Plant (Rize, Turkey),
      were compared for their differences in descriptive sensory analysis (DSA), aroma
      active compounds (volatile compounds), and taste-active compounds (sugar, organic
      acid, and free amino acid compositions). Ten flavor attributes such as 'after
      taste', 'astringency', 'bitter', 'caramel-like', 'floral/sweet', 'green/grassy',
      'hay-like', 'malty', 'roasty', and 'seaweed' were identified. Intensities for a
      number of flavor attributes ('after taste', 'caramel-like', 'malty', and
      'seaweed') were not significantly different (p > 0.05) among seven grades of
      black tea. A total of 57 compounds in seven grades of black tea (14 aldehydes,
      eight alcohols, eight ketones, two esters, four aromatic hydrocarbons, five
      aliphatic hydrocarbons, nine terpenes, two pyrazines, one furan, two acids, and
      two miscellaneous compounds) were tentatively identified. Of these, aldeyhdes
      comprised more than 50% to the total volatile compounds identified. In general,
      high-grade quality tea had more volatiles than low-grade quality tea. With
      respect to taste-active compounds, five sugars, six organic acids, and 18 free
      amino acids were positively identified in seven grades of black tea, of which
      fructose, tannic acid, and theanine predominated, respectively. Some variations
      (p < 0.05), albeit to different extents, were observed among volatile compounds,
      sugars, organic acids, and free amino acids in seven grades of black tea. The
      present study suggests that a certain flavor attributes correlate well with taste
      and aroma-active compounds. High- and low-quality black teas should not be
      distinguished solely on the basis of their DSA and taste- and aroma-active
      compounds. The combination of taste-active compounds together with aroma-active
      compounds renders combination effects that provide the characteristic flavor of
      each grade of black tea.

PMID- 22642546
TI  - Effect of a self-help program for mothers of hemophilic children in Korea.
AB  - Mothers of hemophilic children are under stressful situations because of the
      characteristics of disease and inheritance. The purpose of this study was to
      evaluate the effect of the self-help group program for the mothers of hemophilic
      children. Fifty one mothers of hemophilic children were participated. The
      experiment group (n = 24) participated in the self-help group program for 5
      weeks, while the control group (n = 27) received a self-help booklet only.
      Knowledge, self-efficacy, depression, parenting stress, and quality of life were
      evaluated using questionnaires. Data were analyzed using chi(2) -test, t-test,
      and analysis of covariance (ancova). The experiment and control groups were
      homogeneous in general characteristics and depending variables except knowledge
      (P < 0.05; P > 0.05, respectively). Knowledge, self-efficacy, and quality of life
      in the experiment group were increased after the program (P < 0.001). Especially,
      the knowledge in the experiment group was lower than the control group in
      pretest, but higher in the posttest (P < 0.001). Depression and parenting stress
      were reduced in the experiment group compared to the control group (P < 0.001).
      It is suggestive that the self-help group program can be a useful opportunity for
      mothers of hemophilic children to improve knowledge and self-efficay of child
      care and quality of life of themselves; to decrease depression and parenting
      stress. Extended application of the program to fathers or all family members may
      be needed to investigate in the future.

PMID- 22642547
TI  - Specific detection of integrin alphavbeta3 by light-up bioprobe with aggregation
      induced emission characteristics.
AB  - Specific bioprobes with fluorescence turn-on response are highly desirable for
      high contrast biosensing and imaging. In this work, we developed a new generation
      bioprobe by integrating tetraphenylsilole, a fluorogenic unit with aggregation
      induced emission (AIE) characteristic, with cyclic arginine-glycine-aspartic acid
      tripeptide (cRGD), a targeting ligand to integrin alpha(v)beta(3) receptor.
      Emission of the AIE probe is switched on upon its specific binding to integrin
      alpha(v)beta(3), which allows quantitative detection of integrin alpha(v)beta(3)
      in solution and real-time imaging of the binding process between cRGD and
      integrin alpha(v)beta(3) on cell membrane. The probe can be used for tracking
      integrin alpha(v)beta(3) and for identifying integrin alpha(v)beta(3)-positive
      cancer cells.

PMID- 22642548
TI  - When group membership gets personal: a theory of identity fusion.
AB  - Identity fusion is a relatively unexplored form of alignment with groups that
      entails a visceral feeling of oneness with the group. This feeling is associated
      with unusually porous, highly permeable borders between the personal and social
      self. These porous borders encourage people to channel their personal agency into
      group behavior, raising the possibility that the personal and social self will
      combine synergistically to motivate pro-group behavior. Furthermore, the strong
      personal as well as social identities possessed by highly fused persons cause
      them to recognize other group members not merely as members of the group but also
      as unique individuals, prompting the development of strong relational as well as
      collective ties within the group. In local fusion, people develop relational ties
      to members of relatively small groups (e.g., families or work teams) with whom
      they have personal relationships. In extended fusion, people project relational
      ties onto relatively large collectives composed of many individuals with whom
      they may have no personal relationships. The research literature indicates that
      measures of fusion are exceptionally strong predictors of extreme pro-group
      behavior. Moreover, fusion effects are amplified by augmenting individual agency,
      either directly (by increasing physiological arousal) or indirectly (by
      activating personal or social identities). The effects of fusion on pro-group
      actions are mediated by perceptions of arousal and invulnerability. Possible
      causes of identity fusion--ranging from relatively distal, evolutionary, and
      cultural influences to more proximal, contextual influences--are discussed.
      Finally, implications and future directions are considered.

PMID- 22642549
TI  - Positive correlation between motion analysis data on the LapMentor virtual
      reality laparoscopic surgical simulator and the results from videotape assessment
      of real laparoscopic surgeries.
AB  - PURPOSE: We studied the construct validity of the LapMentor, a virtual reality
      laparoscopic surgical simulator, and the correlation between the data collected
      on the LapMentor and the results of video assessment of real laparoscopic
      surgeries. MATERIALS AND METHODS: Ninety-two urologists were tested on basic
      skill tasks No. 3 (SK3) to No. 8 (SK8) on the LapMentor. They were divided into
      three groups: Group A (n=25) had no experience with laparoscopic surgeries as a
      chief surgeon; group B (n=33) had <35 experiences; and group C (n=34) had >=35
      experiences. Group scores on the accuracy, efficacy, and time of the tasks were
      compared. Forty physicians with >=20 experiences supplied unedited videotapes
      showing a laparoscopic nephrectomy or an adrenalectomy in its entirety, and the
      videos were assessed in a blinded fashion by expert referees. Correlations
      between the videotape score (VS) and the performances on the LapMentor were
      analyzed. RESULTS: Group C showed significantly better outcomes than group A in
      the accuracy (SK5) (P=0.013), efficacy (SK8) (P=0.014), or speed (SKs 3 and 8)
      (P=0.009 and P=0.002, respectively) of the performances of LapMentor. Group B
      showed significantly better outcomes than group A in the speed and efficacy of
      the performances in SK8 (P=0.011 and P=0.029, respectively). Analyses of motion
      analysis data of LapMentor demonstrated that smooth and ideal movement of
      instruments is more important than speed of the movement of instruments to
      achieve accurate performances in each task. Multiple linear regression analysis
      indicated that the average score of the accuracy in SK4, 5, and 8 had significant
      positive correlation with VS (P=0.01). CONCLUSIONS: This study demonstrated the
      construct and predictive validity of the LapMentor basic skill tasks, supporting
      their possible usefulness for the preclinical evaluation of laparoscopic skills.

PMID- 22642550
TI  - Star-shaped trimeric quaternary ammonium bromide surfactants: adsorption and
      aggregation properties.
AB  - Novel star-shaped trimeric surfactants consisting of three quaternary ammonium
      surfactants linked to a tris(2-aminoethyl)amine core were synthesized. Each
      ammonium had two methyls and a straight alkyl chain of 8, 10, 12, or 14 carbons.
      The adsorption and aggregation properties of these tris(N-alkyl-N,N-dimethyl-2
      ammoniumethyl)amine bromides (3C(n)trisQ, in which n represents alkyl chain
      carbon number) were characterized by equilibrium and dynamic surface tension,
      rheology, small-angle neutron scattering (SANS), and cryogenic transmission
      electron microscopy (cryo-TEM) techniques. 3C(n)trisQ showed critical micelle
      concentrations (CMC) 1 order of magnitude lower than that of the corresponding
      gemini surfactants with an ethylene spacer and the corresponding monomeric
      surfactants. The logarithm of the CMC decreased linearly with increasing
      hydrocarbon chain length for 3C(n)trisQ. The slope of the line, which is well
      known as Klevens equation, was larger than those of the monomeric and gemini
      surfactants; however, considering the total carbon number in the chains, the
      slope was shallower than the monomeric and was close to the gemini. Through the
      results such as surface tensions at the CMC (32-34 mN m(-1)) and the parameters
      of standard free energy, CMC/C(20) and pC(20), it was found that 3C(n)trisQ could
      adsorb densely at the air/water interface despite the strong electrostatic
      repulsion between multiple quaternary ammonium headgroups. Moreover, dynamic
      surface tension measurements showed that the kinetics of adsorption for
      3C(n)trisQ to the air/water interface was slow because of their bulky structures.
      Furthermore, the results of rheology, SANS, and cryo-TEM determined that
      3C(n)trisQ with n = 10 and 12 formed ellipsoidal micelles at low concentrations
      in solution and the structures transformed to threadlike micelles with very few
      branches for n = 12 as the concentration increased, but for n = 14 threadlike
      micelles formed at relatively low concentrations.

PMID- 22642551
TI  - Purification and antiradical properties of the structural unit of betalains.
AB  - Betalamic acid [4-(2-oxoethylidene)-1,2,3,4-tetrahydropyridine-2,6-dicarboxylic
      acid] is a naturally occurring compound that is normally found condensed with
      amino acids, amines, cyclo-DOPA, and cyclo-DOPA derivatives to form the
      betalains. Betalains are the pigments responsible for the yellow to violet color
      of the fruits and flowers of plants belonging to the order Caryophyllales.
      Betalamic acid is the structural feature common to all of these pigments and
      contains the electron resonance system responsible for the spectroscopic
      properties. Betalamic acid was purified by chromatography and identified by UV
      vis spectrophotometry and ESI mass spectrometry. The antioxidant and free radical
      scavenging capacities of betalamic acid were assessed using the FRAP and ABTS(.+)
      radical assays. A pK(a) of 6.8 was found for the deprotonation equilibrium
      involved in the nucleophilic activity of betalamic acid; this pK(a) explains the
      observed pH effect on the free radical scavenging capacity of these pigments.

PMID- 22642552
TI  - Limited-information goodness-of-fit testing of hierarchical item factor models.
AB  - In applications of item response theory, assessment of model fit is a critical
      issue. Recently, limited-information goodness-of-fit testing has received
      increased attention in the psychometrics literature. In contrast to full
      information test statistics such as Pearson's X(2) or the likelihood ratio G(2) ,
      these limited-information tests utilize lower-order marginal tables rather than
      the full contingency table. A notable example is Maydeu-Olivares and
      colleagues'M2 family of statistics based on univariate and bivariate margins.
      When the contingency table is sparse, tests based on M2 retain better Type I
      error rate control than the full-information tests and can be more powerful.
      While in principle the M2 statistic can be extended to test hierarchical
      multidimensional item factor models (e.g., bifactor and testlet models), the
      computation is non-trivial. To obtain M2 , a researcher often has to obtain (many
      thousands of) marginal probabilities, derivatives, and weights. Each of these
      must be approximated with high-dimensional numerical integration. We propose a
      dimension reduction method that can take advantage of the hierarchical factor
      structure so that the integrals can be approximated far more efficiently. We also
      propose a new test statistic that can be substantially better calibrated and more
      powerful than the original M2 statistic when the test is long and the items are
      polytomous. We use simulations to demonstrate the performance of our new methods
      and illustrate their effectiveness with applications to real data.

PMID- 22642553
TI  - Comparison of real-time three-dimensional echocardiography and spatiotemporal
      image correlation in assessment of fetal interventricular septum.
AB  - OBJECTIVE: To compare the role of real-time 3DE and STIC technology in assessment
      of the fetal IVS. METHODS: Fifty pregnant women with singleton pregnancies were
      invited to attend this study. All the fetuses were examined by both
      spatiotemporal image correlation and real-time three-dimensional
      echocardiography. There were totally six images of IVS obtained for each fetus:
      live xPlane image, live 3D image, multiplanar image and rendered image with the
      four-chamber view as the starting plane, multiplanar image and rendered image
      with the sagittal view of the fetal thorax as the starting plane. These images
      were grouped into six groups and randomized within each group for the further
      analysis. The images were scored and compared according to the image quality, the
      outline of the fetal IVS and motion artefact. The operator was also asked to
      judge whether VSD existed or not and the results were compared with the final
      diagnosis. The sensitivity, specificity, false positive percentage, positive
      likelihood ratio, false negative percentage and negative likelihood ratio of each
      group were also calculated. RESULTS: There were 15 cases with VSD and four cases
      without VSD in CHD fetus and 31 cases of normal fetus enrolled in this study. A
      total 300 images of the lateral view of fetal IVS were obtained and grouped into
      six groups. The image quality in the group of STIC with the four-chamber view as
      the starting plane is much worse than the group of STIC with the sagittal view as
      the starting plane and real-time three-dimensional echocardiography (P < 0.05).
      There were no significant differences in image quality between the group of STIC
      with the sagittal view as the starting plane and real-time three-dimensional
      echocardiography (P > 0.05). CONCLUSION: The image quality of real-time 3DE is
      similar to the images acquired by STIC from the sagittal view and superior to
      that obtained by STIC from the four-chamber view. However, real-time 3DE has no
      motion artefact, which has the potentials to improve the detection rate of fetal
      VSD.

PMID- 22642554
TI  - Obesity: lessons from evolution and the environment.
AB  - The 9th Stock Conference acknowledged the complex background of genetic,
      cultural, environmental and evolutionary factors of obesity. Gene-environment
      interactions underlie the flexibility in body-weight and body-fat regulation,
      illustrated by the hunter-gatherers' feast and famine lifestyle, the variation in
      physical activity over the lifespan being highest at reproductive age, the
      variation in energy intake through 'eating in the absence of hunger', while
      running the risk of exceeding the capacity of triacylglyceride storage, leading
      to lipotoxicity and metabolic problems. Perinatal metabolic programming for
      obesity via epigenetic changes in response to a 'Western diet' results in
      production of lipid-poor milk and metabolically efficient pups, contributing to
      the perpetuation of obesity throughout generations. Evolutionary insight from
      comparative physiology and ecology indicates that over generations activity
      induced energy expenditure has remained the same compared to wild mammals, that
      energy balance might be dependant on protein balance, while the function of taste
      changed from detection of poison or energy to social drinking and social
      behaviour. At present, the impact of assortative mating on obesity prevalence is
      unambiguously positive. The complexity that appeared can only be fully
      appreciated by setting the data into the context of our evolutionary history.

PMID- 22642555
TI  - Antioxidant activity of capsaicinoid in canola oil.
AB  - Interest in replacing synthetic antioxidants, namely, butylated hydroxytoluene
      (BHT) and butylated hydroxyanisole (BHA), with natural antioxidants is
      increasing. The present study examined the antioxidant activity of capsaicinoid
      from chili pepper in heated canola oil. The oxidation was conducted at 60, 90,
      120, and 180  degrees C by monitoring oxygen consumption and the decrease in
      linoleic acid and alpha-linolenic acid in canola oil. At 60  degrees C,
      capsaicinoid was more effective against oxidation of canola oil compared with
      BHT. At higher temperatures of 90, 120, and 180  degrees C, capsaicinoid
      possessed an antioxidant activity similar to or slightly weaker that that of BHT.
      It was found that capsaicinoid prevented canola oil from oxidation in a dose
      dependent manner. To study the structure-antioxidant relationship, it was found
      that the trimethylsiloxy (TMS) derivatives of capsaicinoid did not exhibit any
      antioxidant activity, suggesting the hydroxyl moiety was the functional group
      responsible for the antioxidant activity of capsaicinoid. It was concluded that
      capsaicinoid had the potential to be further explored as a natural antioxidant in
      foods, particularly spicy foods.

PMID- 22642556
TI  - Desulfovibrio vulgaris bacterioferritin uses H(2)O(2) as a co-substrate for iron
      oxidation and reveals DPS-like DNA protection and binding activities.
AB  - A gene encoding Bfr (bacterioferritin) was identified and isolated from the
      genome of Desulfovibrio vulgaris cells, and overexpressed in Escherichia coli. In
      vitro, H(2)O(2) oxidizes Fe(2+) ions at much higher reaction rates than O(2). The
      H(2)O(2) oxidation of two Fe(2+) ions was proven by Mossbauer spectroscopy of
      rapid freeze-quenched samples. On the basis of the Mossbauer parameters of the
      intermediate species we propose that D. vulgaris Bfr follows a mineralization
      mechanism similar to the one reported for vertebrate H-type ferritins subunits,
      in which a diferrous centre at the ferroxidase site is oxidized to diferric
      intermediate species, that are subsequently translocated into the inner
      nanocavity. D. vulgaris recombinant Bfr oxidizes and stores up to 600 iron atoms
      per protein. This Bfr is able to bind DNA and protect it against hydroxyl radical
      and DNase deleterious effects. The use of H(2)O(2) as an oxidant, combined with
      the DNA binding and protection activities, seems to indicate a DPS (DNA-binding
      protein from starved cells)-like role for D. vulgaris Bfr.

PMID- 22642557
TI  - A strategy for carrier detection in Pakistani haemophilia B families.

PMID- 22642558
TI  - Direct fluorescence monitoring of the delivery and cellular uptake of a cancer
      targeted RGD peptide-appended naphthalimide theragnostic prodrug.
AB  - Presented here is a multicomponent synthetic strategy that allows for the direct,
      fluorescence-based monitoring of the targeted cellular uptake and release of a
      conjugated therapeutic agent. Specifically, we report here the design, synthesis,
      spectroscopic characterization, and preliminary in vitro biological evaluation of
      a RGD peptide-appended naphthalimide pro-CPT (compound 1). Compound 1 is a
      multifunctional molecule composed of a disulfide bond as a cleavable linker, a
      naphthalimide moiety as a fluorescent reporter, an RGD cyclic peptide as a cancer
      targeting unit, and camptothecin (CPT) as a model active agent. Upon reaction
      with free thiols in aqueous media at pH 7.4, disulfide cleavage occurs. This
      leads to release of the free CPT active agent, as well as the production of a red
      shifted fluorescence emission (lambda(max) = 535 nm). Confocal microscopic
      experiments reveal that 1 is preferentially taken up by U87 cells over C6 cells.
      On the basis of competition experiments involving okadaic acid, an inhibitor of
      endocytosis, it is concluded that uptake takes place via RGD-dependent
      endocytosis mechanisms. In U87 cells, the active CPT payload is released within
      the endoplasmic reticulum, as inferred from fluorescence-based colocalization
      studies using a known endoplasmic reticulum-selective dye. The present drug
      delivery system (DDS) could represent a new approach to so-called theragnostic
      agent development, wherein both a therapeutic effect and drug uptake-related
      imaging information are produced and can be readily monitored at the subcellular
      level. In due course, the strategy embodied in conjugate 1 could allow for more
      precise monitoring of dosage levels, as well as an improved understanding of
      cellular uptake and release mechanisms.

PMID- 22642559
TI  - Transparent electrodes fabricated via the self-assembly of silver nanowires using
      a bubble template.
AB  - To shore up the demand of transparent electrodes for wide applications such as
      organic light emitting diodes and solar cells, transparent electrodes are
      required as an alternative for indium tin oxide electrodes. Herein the self
      assembly method with a bubble template paves the way for cost-effective
      fabrication of transparent electrodes with high conductivity and transparency
      using self-assembly of silver nanowires (AgNWs) in a bubble template. AgNWs were
      first dispersed in water that was bubbled with a surfactant and a thickening
      agent. Furthermore, these AgNWs were assembled by lining along the bubble ridges.
      When the bubbles containing the AgNWs were sandwiched between two glass
      substrates, the bubble ridges including the AgNWs formed continuous polygonal
      structures. Mesh structures were formed on both glass substrates after air
      drying. The mesh structures evolved into mesh transparent electrodes following
      heat-treatment. The AgNW mesh structure exhibited a low sheet resistance of 6.2
      Omega/square with a transparency of 84% after heat treatment at 200  degrees C
      for 20 min. The performance is higher than that of transparent electrodes with
      random networks of AgNWs. Furthermore, the conductivity and transparency of the
      mesh transparent electrodes can be adjusted by changing the amount of the AgNW
      suspension and the space between the two glass substrates.

PMID- 22642560
TI  - Daphmacromines A-J, alkaloids from Daphniphyllum macropodum.
AB  - Ten new yuzurine-type Daphniphyllum alkaloids, daphmacromines A-J (1-10), along
      with seven known alkaloids were isolated from the leaves and stems of
      Daphniphyllum macropodum. Their structures were elucidated by extensive
      spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry,
      and the structure of 1 was confirmed by single-crystal X-ray diffraction. The
      pesticidal and cytotoxic activities of the isolated alkaloids were evaluated in
      vitro against brine shrimp (Artemia salina) and five human cancer cell lines (HL
      60, SMMC-7721, A-549, MCF-7, and SW480), respectively. This study also suggested
      structural revisions of oxodaphnigracine, oxodaphnigraciline, and
      epioxodaphnigraciline.

PMID- 22642561
TI  - Description and validation of a modular training system for laparoscopic
      nephrectomy.
AB  - BACKGROUND AND PURPOSE: Laparoscopic nephrectomy (LN) has largely replaced open
      nephrectomy. The aim of this study was to describe a validated modular system for
      training urologists in LN in the context of the shorter training times available
      in the current era. METHODS: After attendance at dry and wet laboratory courses,
      three mentees (trainee, new consultant, and an experienced open surgeon) were
      mentored through a five-module LN training system in our center followed by the
      mentee's own hospital. A minimum of 25 independent procedures were then performed
      by mentees in their own hospital. RESULTS: There were 17 to 32 mentored cases
      needed to become competent in LN, followed by up to 5 observed cases in the
      mentee's own center. Subsequently, data from the first 105 cases (80 LN and 25
      laparoscopic nephroureterectomies [LNU]) performed by the three surgeons after
      the end of their training without observation by their mentor were
      retrospectively collected and analyzed. There were three conversions (2.9%). For
      LN and LNU, respectively: median operative time was 140 minutes (65-390 min) and
      180 minutes (90-300 min); median estimated blood loss was 30 mL (0-2000 mL) and
      50 mL (0-2000 mL); median postoperative stay was 4 days (2-45 days) and 6 days (3
      27 days). Four (3.8%) patients needed a postoperative transfusion. There was no
      30-day mortality. CONCLUSION: Mentees matched the median British Association for
      Urological Surgeons (BAUS) registry operative time (LN, 120-180 min, LNU, 180-240
      min) and had lower conversion rates (2.9% vs 6.4% for BAUS). Mentees matched
      median BAUS database reported blood loss (LN and LNU <500 mL) and length of stay
      (LN-4 days, LNU-5 days). This modular training program allows urologists to
      become independent in LN after a short period of focused training in the training
      center followed by a short period of mentoring in the mentee's own center.

PMID- 22642562
TI  - Ischemia-modified albumin (IMA): could it be useful to predict perinatal
      asphyxia?
AB  - Perinatal asphyxia is a significant cause of perinatal morbidity and mortality
      worldwide. It is estimated that around 23% of all newborn deaths are caused by
      birth asphyxia. Each year, between four and nine million newborns develop birth
      asphyxia worldwide, according to the World Health Organization (WHO). Therefore,
      despite major advances in monitoring and knowledge of fetal and neonatal
      physiology and development, perinatal asphyxia remains a serious condition that
      causes significant mortality and long-term morbidity. However, to date no single
      marker of perinatal asphyxia has shown good predictive efficacy in prediction and
      early diagnosis of perinatal asphyxia. On the other hand, ischemia-modified
      albumin (IMA) is a new biomarker in identification of myocardial ischemia of
      myocardial necrosis. IMA may also increase in the ischemia of liver, brain,
      kidney and bowel. Ischemia of these organs may also seen in perinatal asphyxia as
      well. Reactive oxygen species, produced during ischaemia/reperfusion which is
      essential steps of perinatal asphyxia, may generate the highly reactive hydroxyl
      radicals. These hydroxyl radicals modify the albumin and transforms it into IMA.
      Therefore, IMA might be useful for the prediction and diagnosis of perinatal
      asphyxia. Further studies are urgently needed to determine the role of IMA in the
      prediction of perinatal asphyxia.

PMID- 22642563
TI  - Factors affecting decision making about fertility preservation after cancer
      diagnosis: a qualitative study.
AB  - OBJECTIVE: To increase our understanding of factors underlying the decision to
      store gametes after the diagnosis of cancer. DESIGN: Qualitative interview study.
      SETTING: Andrology, Haematology, and Oncology Departments of a Scottish teaching
      hospital, and patients' own homes. POPULATION: Sixteen men and 18 women aged 17
      49 years recently diagnosed with cancer; 15 health professionals concerned in
      cancer care. METHODS: Audio-recorded semi-structured interviews were transcribed
      verbatim and analysed thematically. Topics included perceptions of diagnosis;
      prognosis; future reproductive choices; priorities; quality of information
      received; communication and decisions made about future reproductive choices; and
      the role of partners, family, friends and healthcare professionals. Professional
      interviews examined their role in decision making and that of protocols and
      guidelines, together with information emerging from patient interview analysis.
      MAIN OUTCOME MEASURE: Themes identified following analysis of interview
      transcripts. RESULTS: The primary barriers to pursuing fertility preservation
      were the way in which information was provided and the 'urgent need for
      treatment' conveyed by staff. Survival was always viewed as paramount, with
      future fertility secondary. Sperm banking was viewed as 'part and parcel' of
      oncology care, and the majority of men quickly stored sperm as 'insurance'
      against future infertility. Few women were afforded the opportunity to discuss
      their options, reflecting clinicians' reservations about the experimental nature
      of egg and ovarian tissue cryopreservation, and the need for partner involvement
      in embryo storage. CONCLUSIONS: Significant gaps in the information provided to
      young women diagnosed with cancer suggest the need for an early appointment with
      a fertility expert.

PMID- 22642564
TI  - An unbalanced maternal diet in pregnancy associates with offspring epigenetic
      changes in genes controlling glucocorticoid action and foetal growth.
AB  - OBJECTIVE: In epidemiological studies, adverse early-life conditions associate
      with subsequent cardiometabolic disease. Hypothesized causes include maternal
      malnutrition, foetal glucocorticoid overexposure and reduced growth factors.
      Animal studies suggest a role for epigenetic processes in maintaining early-life
      effects into adulthood, but human relevance is unknown. We aimed to investigate
      relationships between an unbalanced maternal diet in pregnancy, neonatal and
      adult anthropometric variables with methylation at key genes controlling tissue
      glucocorticoid action and foetal growth. DESIGN: We studied 34 individuals aged
      40 from the Motherwell cohort study whose mothers ate an unbalanced diet in
      pregnancy, previously linked with elevated blood pressure and cortisol in adult
      offspring. MEASUREMENTS: DNA methylation at 11beta-hydroxysteroid dehydrogenase
      type 2 (HSD2), glucocorticoid receptor (GR) and insulin-like growth factor 2
      (IGF2) was measured by pyrosequencing on buffy coat DNA. RESULTS: Methylation at
      specific CpGs in the HSD2 promoter and at one of the IGF2 differentially
      methylated regions (H19 ICR) correlated with neonatal anthropometric variables.
      CpG methylation within HSD2, GR and H19 ICR was positively associated with
      increased adiposity and blood pressure in adulthood. Methylation at GR (exon 1F)
      was increased in offspring of mothers with the most unbalanced diets in
      pregnancy. CONCLUSIONS: Alterations in DNA methylation at genes important in
      regulating circulating cortisol levels, tissue glucocorticoid action, blood
      pressure and foetal growth are present in adulthood in association with both
      early-life parameters and cardiometabolic risk factors. The data indicate a
      persisting epigenetic link between early-life maternal diet and/or foetal growth
      and cardiovascular disease risk in humans.

PMID- 22642565
TI  - Prevalence of depression in adults with haemophilia.
AB  - Multiple factors place adults with haemophilia at risk for depression. Health
      outcomes can be compromised in depressed patients secondary to increased risk
      taking behaviour and poor compliance with treatment recommendations. To assess
      the prevalence and risk factors associated with depression in adult patients with
      haemophilia treated at a haemophilia treatment centre. Adults with haemophilia
      were screened for depression during their annual clinic visit using the Patient
      Health Questionnaire 9 (PHQ-9), a validated tool for depression screening in
      adults. Depression was defined as a PHQ-9 score >= 5. Risk factors associated
      with depression were collected by chart review and correlated with depression
      scores. A total of 41 adult patients consented to the study and 37% met criteria
      for depression. Fifty-three per cent of patients with depression reported
      moderate to severe symptoms of depression (PHQ-9 score >10). Seventy-six per cent
      of patients with depression reported suffering functional impairment due to their
      depressive symptoms. Lack of social support and unemployment were significantly
      associated with higher PHQ-9 scores (P = 0.04 and P = 0.01 respectively). Adult
      patients with haemophilia have a high prevalence of depression. The addition of
      depression screening to the comprehensive care of adults with haemophilia may
      result in improved overall health outcomes and treatment adherence.

PMID- 22642566
TI  - Reaction-based genetically encoded fluorescent hydrogen sulfide sensors.
AB  - The detection of hydrogen sulfide (H(2)S), a toxic gas and an important
      biological signaling molecule, has been a long-time challenge. Here we report
      genetically encoded fluorescent protein (FP)-based probes that can selectively
      detect H(2)S. By expanding the genetic codes of E. coli and mammalian cells, FP
      chromophores were modified with the sulfide-reactive azide functional group.
      These structurally modified chromophores were selectively reduced by H(2)S,
      resulting in sensitive fluorescence enhancement detectable by spectroscopic and
      microscopic techniques. Exploration of a circularly permuted FP led to an
      improved sensor with faster responses, and the feasibility of using such a
      genetically encoded probe to monitor H(2)S in living mammalian cells has also
      been demonstrated.

PMID- 22642567
TI  - Revealing a natural marine product as a novel agonist for retinoic acid receptors
      with a unique binding mode and inhibitory effects on cancer cells.
AB  - Retinoids display anti-tumour activity on various cancer cells and therefore have
      been used as important therapeutic agents. However, adverse side effects and RA
      (retinoic acid) resistance limit further development and clinical application of
      retinoid-based therapeutic agents. We report in the present paper the
      identification of a natural marine product that activates RARs (RA receptors)
      with a chemical structure distinct from retinoids by high-throughput compound
      library screening. Luffariellolide was uncovered as a novel RAR agonist by
      inducing co-activator binding to these receptors in vitro, further inhibiting
      cell growth and regulating RAR target genes in various cancer cells. Structural
      and molecular studies unravelled a unique binding mode of this natural ligand to
      RARs with an unexpected covalent modification on the RAR. Functional
      characterization further revealed that luffariellolide displays chemotherapeutic
      potentials for overcoming RA resistance in colon cancer cells, suggesting that
      luffariellolide may represent a unique template for designing novel non-retinoid
      compounds with advantages over current RA drugs.

PMID- 22642568
TI  - Flexible ureteroscopy and laser lithotripsy for stones >2 cm: a systematic review
      and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Urinary stones >2 cm are traditionally managed with
      percutaneous nephrolithotomy (PCNL). Recently, flexible ureteroscopy and laser
      lithotripsy) (FURSL) has been used to manage them with comparable results. In a
      comparative study of renal stones between 2 and 3 cm, FURSL was reported to need
      less second-stage procedures and be just as effective as PCNL. Our purpose was to
      review the literature for renal stones >2 cm managed by ureteroscopy and holmium
      lasertripsy. MATERIALS AND METHODS: A systematic review and quantitative meta
      analysis was performed using studies identified by a literature search from 1990s
      (the first reported large renal stones treated ureteroscopically) to August 2011.
      All English language articles reporting on a minimum of 10 patients treated with
      FURSL for renal stones >2 cm were included. Two reviewers independently extracted
      the data from each study. The data of studies with comparable results were
      included into a meta-analysis. RESULTS: In nine studies, 445 patients (460 renal
      units) were reportedly treated with FURSL. The mean operative time was 82.5
      minutes (28-215 min). The mean stone-free rate was 93.7% (77%-96.7%), with an
      average of 1.6 procedures per patient. The mean stone size was 2.5 cm. An overall
      complication rate was 10.1%. Major complications developed in 21 (5.3%) patients
      and minor complications developed in 19 (4.8%) patients. A subgroup analysis
      shows that FURSL has a 95.7% stone-free rate with stones 2-3 cm and 84.6% in
      those >3 cm (P=0.01), with a minor complication rate of 14.3% and 15.4%,
      respectively, and a major complication rate of 0% and 11.5%, respectively.
      CONCLUSION: In experienced hands, FURSL can successfully treat patients with
      stones >2 cm with a high stone-free rate and a low complication rate. Although
      the studies are from high-volume experienced centers and may not be sufficient to
      alter everyday routine practice, this review has shown that the efficacy of FURSL
      allows an alternative to PCNL.

PMID- 22642569
TI  - Cyclophilin A and nuclear factor of activated T cells are essential in
      cyclosporine-mediated suppression of polyomavirus BK replication.
AB  - Immunosuppressants have impacts on the development of polyomavirus-associated
      nephropathy. We previously demonstrated that cyclosporin A (CsA) suppressed
      polyomavirus BK (BKV) replication. The role of cyclophilin A (CypA) and nuclear
      factor of activated T cells (NFAT) in CsA-imposed suppression of BKV replication
      was determined in this study. Results demonstrated that knockdown of CypA but not
      CypB significantly reduced BKV large T antigen (TAg) expression and BKV titer.
      Overexpression of CypA reversed CypA siRNA-induced inhibition in BKV TAg
      expression. In addition, CypA overexpression attenuated the suppressive effect of
      CsA on TAg expression, suggesting CypA implicated in CsA-mediated anti-BKV
      effect. Knockdown of NFATc3 abrogated TAg expression, while overexpression of
      NFATc3 promoted TAg expression and augmented BKV promoter activity. NFATc3
      binding to the BKV promoter was verified by chromatin immunoprecipitation assay
      and electrophoretic mobility shift assay. Renal histology also displayed an
      increase in NFATc3 expression in tubulointerstitium of BKV-associated
      nephropathy. Furthermore, overexpression of NFATc3 rescued CsA-mediated
      inhibition of BKV load and TAg expression. A CsA analog, NIM811, which cannot
      block NFAT functionality, failed to suppress TAg expression. In conclusion, CypA
      and NFAT are indispensable in BKV replication. CsA inhibits BKV replication
      through CypA and NFAT, which may be potential targets of anti-BKV treatment.

PMID- 22642571
TI  - Post-earthquake birth-rate evaluation using the brief cope.
AB  - BACKGROUND: The study arises from the idea of analyzing the reasons why many
      women in L'Aquila decided to conceive in the months following the 2009
      earthquake. In the months from January to June 2011, there was a +27.24% increase
      in the number of newborns (+ 91) delivered in the Obstetrics and Gynecology Unit
      of the San Salvatore Hospital of L'Aquila compared to the same six-month period
      in 2010. METHODS: Between January 2010 and December 2010, 874 women gave birth in
      L'Aquila. The women living outside of L'Aquila were excluded from the study. The
      remaining women, namely a sample of 451 individuals, were administered a
      questionnaire that focused on the level of stress experienced during the
      earthquake, and subsequently the Brief Cope. RESULTS: After the earthquake there
      was a +22.64% increase in the number of women who desired a pregnancy. The
      results of the Brief Cope show that the coping strategies used by the women in
      L'Aquila were active coping, planning, acceptance and positive reframing.
      CONCLUSIONS: The desire for motherhood was the main reason accounting for the
      increase in births that occurred after the earthquake. The decision to have a
      child was the tangible sign of adaptation to the post-traumatic stress.

PMID- 22642570
TI  - Recommendations for the predictive genetic test in Huntington's disease.

PMID- 22642572
TI  - Tailoring the refractive indices of thin film polymer metallic nanoparticle
      nanocomposites.
AB  - We demonstrate how to tailor the spatial distribution of gold nanoparticles (Au
      NPs) of different sizes within polystyrene (PS) thin, supported, film hosts,
      thereby enabling the connection between the spatial distribution of Au-NPs within
      the polymer film and the optical properties to be determined. The real, n, and
      imaginary parts, k, of the complex refractive indices N = n(lambda)+ik(lambda) of
      the nanocomposite films were measured as a function of wavelength, lambda, using
      multivariable angle spectroscopic ellipsometry. The surface plasmon response of
      films containing nearly homogeneous Au-NP distributions were well described by
      predictions based on classical Mie theory and the Drude model. The optical
      spectra of samples containing inhomogeneous nanoparticle distributions manifest
      features associated with differences in the size and interparticle spacings as
      well as the proximity and organization of nanoparticles at the substrate and free
      surface.

PMID- 22642574
TI  - Single-center comparative oncologic outcomes of surgical and percutaneous
      cryoablation for treatment of renal tumors.
AB  - PURPOSE: To compare outcomes between patients undergoing surgical and
      percutaneous cryoablation for treatment of renal masses and identify prognostic
      variables that determine survival. PATIENTS AND METHODS: We retrospectively
      evaluated the medical records of 194 patients who underwent cryoablation for
      renal tumors between 1997 and 2008 at a single large center. Patient
      demographics, tumor characteristics, perioperative data, and follow-up details
      were recorded. Univariate and multivariate Cox proportional hazards analysis was
      performed to identify predictors of overall (OS), cancer-specific (CSS), and
      recurrence-free survival (RFS). RESULTS: Cryoablation was performed
      percutaneously (PCA) in 141 patients for 154 tumors, while 53 patients were
      treated surgically (SCA) using an open or laparoscopic approach for 54 tumors.
      Mean follow-up was 44.5 months in SCA and 36.1 months in PCA. PCA had a shorter
      duration of hospital stay (0.7 days vs 3.2 days, P<0.0001). The rate of residual
      (P=0.38) and recurrent disease (P=0.18) was not significantly different between
      the two groups. Five-year OS, CSS, and RFS were 78.81%, 100%, and 85.23% for SCA,
      and 77.71%, 98%, and 95.56% for PCA, respectively; the type of approach was not
      predictive of OS, CSS, and RFS. CONCLUSIONS: SCA and PCA both provide adequate
      oncologic control for renal masses. Duration of hospital stay was lower in
      patients undergoing PCA.

PMID- 22642575
TI  - The post-transcriptional life of mammalian mitochondrial RNA.
AB  - Mammalian mitochondria contain their own genome that encodes mRNAs for thirteen
      essential subunits of the complexes performing oxidative phosphorylation as well
      as the RNA components (two rRNAs and 22 tRNAs) needed for their translation in
      mitochondria. All RNA species are produced from single polycistronic precursor
      RNAs, yet the relative concentrations of various RNAs differ significantly. This
      underscores the essential role of post-transcriptional mechanisms that control
      the maturation, stability and translation of mitochondrial RNAs. The present
      review provides a detailed summary on the role of RNA maturation in the
      regulation of mitochondrial gene expression, focusing mainly on messenger RNA
      polyadenylation and stability control. Furthermore, the role of mitochondrial
      ribosomal RNA stability, processing and modifications in the biogenesis of the
      mitochondrial ribosome is discussed.

PMID- 22642577
TI  - Glycosylation at Asn91 of H1N1 haemagglutinin affects binding to glycan
      receptors.
AB  - The glycoprotein HA (haemagglutinin) on the surface of influenza A virus plays a
      central role in recognition and binding to specific host cell-surface glycan
      receptors and in fusion of viral membrane to the host nuclear membrane during
      viral replication. Given the abundance of HA on the viral surface, this protein
      is also the primary target for host innate and adaptive immune responses.
      Although addition of glycosylation sites on HA are a part of viral evolution to
      evade the host immune responses, there are specific glycosylation sites that are
      conserved during most of the evolution of the virus. In the present study, it was
      demonstrated that one such conserved glycosylation site at Asn(91) in H1N1 HA
      critically governs the glycan receptor-binding specificity and hence would
      potentially impinge on the host adaptation of the virus.

PMID- 22642576
TI  - Co-ordination of cell cycle and differentiation in the developing nervous system.
AB  - During embryonic development, cells must divide to produce appropriate numbers,
      but later must exit the cell cycle to allow differentiation. How these processes
      of proliferation and differentiation are co-ordinated during embryonic
      development has been poorly understood until recently. However, a number of
      studies have now given an insight into how the cell cycle machinery, including
      cyclins, CDKs (cyclin-dependent kinases), CDK inhibitors and other cell cycle
      regulators directly influence mechanisms that control cell fate and
      differentiation. Conversely, examples are emerging of transcriptional regulators
      that are better known for their role in driving the differentiated phenotype,
      which also play complementary roles in controlling cell cycle progression. The
      present review will summarise our current understanding of the mechanisms co
      ordinating the cell cycle and differentiation in the developing nervous system,
      where these links have been, perhaps, most extensively studied.

PMID- 22642581
TI  - Evaluation of a novel flow chamber system to assess clot formation in factor VIII
      deficient mouse and anti-factor IXa-treated human blood.
AB  - Blood flow properties play important roles in the regulation and formation of
      thrombus. To evaluate the influence of blood flow on thrombus formation in
      haemophilia, whole blood samples were obtained from FVIII-deficient (FVIII(-/-) )
      and wild-type (FVIII(+/+) ) mice (n = 6 respectively), and from six human
      volunteers. Anti-FIXa aptamer was added to human blood to model acquired
      haemophilia B. Recalcified whole blood samples containing corn trypsin inhibitor
      and danaproid were perfused over the microchip coated with collagen and tissue
      thromboplastin at shear rates of 1100 and 110 s(-1) . Thrombus formation in the
      capillary was quantified by monitoring flow pressure changes. The intervals to 5
      kPa (T(5) ) and 40 k Pa (T(40) ) reflect the onset and growth of thrombus
      formation respectively. Furthermore, fibrin and platelets in thrombi were
      quantified by immunostaining. T(5) at both shear rates were similar in FVIII(-/-)
      and FVIII(+/+) mice. T(40) of FVIII(-/-) mice (1569 +/- 565 s) was significantly
      delayed compared with FVIII(+/+) mice (339 +/- 78 s) at 110 s(-1) (P < 0.05), but
      not at 1100 s(-1) . The delay was normalized by adding human FVIII (2 IU mL(-1)
      ). Similarly, adding anti-FIXa aptamer to human blood prolonged T(40) at 110 s(
      1) (P < 0.01), but not at 1100 s(-1) . Impaired production of fibrin due to anti
      FIXa aptamer at 110 s(-1) was shown in the immunostained thrombus. Our perfusion
      experiments demonstrated that shear rates influence thrombus formation patterns
      in haemophilia, and that reduced activity of intrinsic tenase (FIXa-FVIIIa)
      becomes evident under venous shear rates.

PMID- 22642582
TI  - Targeted disruption of exogenous EGFP gene in medaka using zinc-finger nucleases.
AB  - Zinc-finger nucleases (ZFNs) are artificial enzymes that create site-specific
      double-strand breaks and thereby induce targeted genome editing. Here, we
      demonstrated successful gene disruption in somatic and germ cells of medaka
      (Oryzias latipes) using ZFN to target exogenous EGFP genes. Embryos that were
      injected with an RNA sequence pair coding for ZFNs showed mosaic loss of green
      fluorescent protein fluorescence in skeletal muscle. A number of mutations that
      included both deletions and insertions were identified within the ZFN target site
      in each embryo, whereas no mutations were found at the non-targeted sites. In
      addition, ZFN-induced mutations were introduced in germ cells and efficiently
      transmitted to the next generation. The mutation frequency varied (6-100%) in the
      germ cells from each founder, and a founder carried more than two types of
      mutation in germ cells. Our results have introduced the possibility of targeted
      gene disruption and reverse genetics in medaka.

PMID- 22642584
TI  - Importance of hierarchical structures in wetting stability on submersed
      superhydrophobic surfaces.
AB  - Submersed superhydrophobic surfaces exhibit great potential for reducing flow
      resistance in microchannels and drag of submersed bodies. However, the low
      stability of liquid-air interfaces on those surfaces limits the scope of their
      application, especially under high liquid pressure. In this paper, we first
      investigate the wetting states on submersed hydrophobic surfaces with one-level
      structure under hydrostatic pressure. Different equilibrium states based on free
      energy minimization are formulated, and their stabilities are analyzed as well.
      Then, by comparison with the existing numerical and experimental studies, we
      confirm that a new metastable state, which happens after depinning of the three
      phase contact line (TCL), exists. Finally, we show that a strategy of using
      hierarchical structures can strengthen the TCL pinning of the liquid-air
      interface in the metastable state. Therefore, the hierarchical structure on
      submersed surfaces is important to further improve the stability of
      superhydrophobicity under high liquid pressure.

PMID- 22642583
TI  - Driving safety: concerns and experiences of parents of adolescent drivers with
      type 1 diabetes.
AB  - Driving is a dangerous activity for adolescents, perhaps being even more
      precarious for adolescents with type 1 diabetes due to the possibility of extreme
      blood glucose (BG). There is no available data on adolescent driving safety
      concerns and type 1 diabetes. To begin addressing this issue, we surveyed parents
      regarding their observations and concerns. Seventy-two parents (87.5% mothers) of
      adolescent drivers aged 16-19 with type 1 diabetes provided analyzable data.
      Females comprised 36% of their adolescents, with 74% using pump therapy. In the
      past year, 13 and 84% of parents reported that their adolescent had experienced
      severe or moderate disruptive hypoglycemia, respectively. Over half (56%) of the
      parents reported moderate to extreme worry about how diabetes impacted their
      adolescent's driving, while only 21% of parents thought their adolescents had
      similar concerns (p = 0.037). Almost one third (31%) of parents thought their
      adolescent need not treat low BG until it fell below 70 mg/dL, 13% thought their
      adolescent could safely drive with BG below 65 mg/dL. And, 31 and 14% of parents,
      respectively, reported their adolescent had been in a collision or stopped by the
      police in the past year, which they attributed to both hypo- and hyperglycemia.
      Adolescents reportedly took steps to prevent hypo- and hyperglycemia while
      driving, but more aggressively avoided hypoglycemia (p < 0.001). While this data
      is limited, lacking a non-diabetic control group and randomized sample, it does
      suggest that driving and adolescent type 1 diabetes deserve further attention and
      investigation.

PMID- 22642585
TI  - Cost satisfaction analysis: a novel patient-based approach for economic analysis
      of the utility of fixed prosthodontics.
AB  - The aim of this study was to apply a novel economic tool (cost satisfaction
      analysis) to assess the utility of fixed prosthodontics, to review its
      applicability, and to explore the perceived value of treatment. The cost
      satisfaction analysis employed the validated Patient Satisfaction Questionnaire
      (PSQ). Patients with a known prostheses outcome over 1-20 years were mailed the
      PSQ. Five hundred patients (50.7%) responded. Remembered satisfaction at
      insertion (initial costs) and current satisfaction (costs in hindsight) were
      reported on VAS, and the difference calculated (costs with time). Percentage and
      grouped responses (low, <40%; medium, 40-70%; high, > 70%) were analysed in
      relation to patient gender, age and willingness to have undergone the same
      treatment again, and in relation to prostheses age, type, complexity and outcome.
      Significance was set at P = 0.05. Averages were reported as means +/- standard
      error. Satisfaction with initial costs and costs in hindsight were unrelated to
      patient gender and age, and prostheses age, type and complexity. Patients with a
      failure and those who would elect to not undergo the same treatment again were
      significantly less satisfied with initial costs (P = 0.021, P < 0.001) and costs
      in hindsight (P = 0.021, P < 0.001) than their counterparts. Patient's cost
      satisfaction (entire cohort) had significantly improved from 53 +/- 1% at
      insertion to 81 +/- 0.9% in hindsight (28 +/- 1% improvement, P < 0.001). Patient
      cost satisfaction had also significantly improved, and the magnitude of
      improvement was the same within every individual cohort (P = 0.004 to P < 0.001),
      including patients with failures, and those who in hindsight would not undergo
      the same treatment again. Low satisfaction was reported by 166 patients
      initially, but 94% of these reported improvements in hindsight. Fourteen patients
      (3%) remained dissatisfied in hindsight, although 71% of these would still choose
      to undergo the same treatment again. Cost satisfaction analysis provided an
      evaluation of the patient's perspective of the value of fixed prosthodontic
      treatment. Although fixed prosthodontic treatment was perceived by patients to be
      expensive, it was also perceived to impart value with time. Cost satisfaction
      analysis provides a clinically useful insight into patient behaviour.

PMID- 22642586
TI  - Statement of retraction.

PMID- 22642587
TI  - Langkolide, a 32-membered macrolactone antibiotic produced by Streptomyces sp.
      Acta 3062.
AB  - A new 32-membered macrolactone antibiotic, named langkolide, was isolated from
      the mycelium of Streptomyces sp. Acta 3062. The langkolide structure was
      determined by HR-MS and 1D and 2D NMR as a 32-membered macrolactone connected
      from an overhanging polyketide tail to a naphthoquinone unit mediated by two
      carbohydrate moieties. The producing strain was isolated from a rhizosphere soil
      of Clitorea sp. collected at Burau Bay, Langkawi, Malaysia, and was characterized
      by its morphological and chemotaxonomic features in addition to its 16S rRNA gene
      sequence. It was identified as a member of the Streptomyces galbus clade.
      Langkolide exhibited various bioactivities including antimicrobial and
      antiproliferative activities. Furthermore, langkolide inhibited human recombinant
      phosphodiesterase 4 with an IC(50) value of 0.48 MUM.

PMID- 22642588
TI  - Different effects of sonoporation on cell morphology and viability.
AB  - The objective of our study was to investigate changes in cell morphology and
      viability after sonoporation. Sonoportion was achieved by ultrasound (21 kHz)
      exposure on adherent human prostate cancer DU145 cells in the cell culture dishes
      with the presence of microbubble contrast agents and calcein (a cell impermeant
      dye). We investigated changes in cell morphology immediately after sonoporation
      under scanning electron microscope (SEM) and changes in cell viability
      immediately and 6 h after sonoporation under fluorescence microscope. It was
      shown that various levels of intracellular calcein uptake and changes in cell
      morphology can be caused immediately after sonoporation: smooth cell surface,
      pores in the membrane and irregular cell surface. Immediately after sonoporation,
      both groups of cells with high levels of calcein uptake and low levels of calcein
      uptake were viable; 6 h after sonoporation, group of cells with low levels of
      calcein uptake still remained viable, while group of cells with high levels of
      calcein uptake died. Sonoporation induces different effects on cell morphology,
      intracellular calcein uptake and cell viability.

PMID- 22642589
TI  - Anti-fibrotic effect of Aliskiren in rats with deoxycorticosterone induced
      myocardial fibrosis and its potential mechanism.
AB  - The objective of our study was to investigate the effect of Aliskiren, a renin
      inhibitor, on the deoxycorticosterone (DOCA) induced myocardial fibrosis in a rat
      model and its underlying mechanism. A total of 45 Sprague-Dawley (SD) rats
      underwent right nephrectomy and were randomly assigned into 3 groups: control
      group (CON group: silicone tube was embedded subcutaneously); DOCA treated group
      (DOC group: 200 mg of DOCA was subcutaneously administered); DOCA and Aliskiren
      (ALI) treated group (ALI group: 200 mg of DOCA and 50 mg/kg/d ALI were
      subcutaneously and intragastrically given, respectively). Treatment was done for
      4 weeks. Sirius red staining was employed to detect the expression of myocardial
      collagen, and the myocardial collagen volume fraction (CVF) and perivascular
      collagen volume area (PVCA) were calculated. Radioimmunoassay was carried out to
      measure the renin activity (RA) and content of angiotensin II (Ang II) in the
      plasma and ventricle. Western blot assay was done to detect the expressions of
      extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated ERK1/2
      (PERK1/2) and matrix metalloproteinase 9 (MMP-9). In the DOC group and ALI group,
      the CVF and PVCA were significantly increased; the RA and Ang II levels in the
      plasma and ventricle were remarkably lowered when compared with the CON group.
      The RA and Ang II levels in the ventricle of the ALI group were significantly
      lower than those in the DOC group. Moreover, the expressions of ERK1/2, PERK1/2
      and MMP9 were the lowest in the CON group, but those in the ALI group were
      significantly reduced as compared to the DOC group. ALI can inhibit the DOCA
      induced myocardial fibrosis independent of its pressure-lowing effect, which may
      be related to the suppression of RA and Ang II production, inhibition of ERK1/2
      phosphorylation and MMP9 expression in the heart.

PMID- 22642590
TI  - TFF1 inhibits proliferation and induces apoptosis of gastric cancer cells in
      vitro.
AB  - Trefoil Factor Family (TFF) plays an essential role in the intestinal epithelial
      restitution, but the relationship between TFF1 and gastric cancer (GC) is still
      unclear. The present study aimed to determine the role of TFF1 in repairing
      gastric mucosa and in the pathogenesis of GC.  The TFF1 expression in different
      gastric mucosas was measured with immunohistochemistry. Then, siRNA targeting
      TFF1 or plasmids expressing TFF1 gene were transfected into BGC823 cells, SGC7901
      cells and GES-1 cells. The cell proliferation was detected with MTT assay and
      apoptosis and cell cycle measured by flow cytometry. From normal gastric mucosa
      to mucosa with dysplasia and to gastric cancer, the TFF1 expression had a
      decreasing trend. Down-regulation of TFF1 expression significantly reduced the
      apoptosis of three cell lines and markedly facilitated their proliferation but
      had no significant effect on cell cycle. Over-expression of TFF1 could promote
      apoptosis of three cell lines and inhibit proliferation but had no pronounced
      effect on cell cycle. TFF1 can inhibit proliferation and induce apoptosis of GC
      cells in vitro.

PMID- 22642591
TI  - Prevalence of 1691G>A FV mutation in Poland compared with that in other Central,
      Eastern and South-Eastern European countries.
AB  - The 1691G>A FV variant has been described as a common genetic risk factor in
      venous thromboembolism. The purpose of this study was to provide a further
      frequency value for 1691G>A FV in Poland and to collate summary data from Central
      (Poland, Czech, Slovakia), Eastern (Russia, Belarus, Ukraine) and South-Eastern
      (Slovenia, Croatia, Bosnia and Herzegovina, Serbia, Montenegro, Macedonia,
      Bulgaria) European countries. For this purpose in 2007 the 1691G>A FV variant was
      analyzed by polymerase chain reaction-restriction fragment length polymorphism
      from DNA collected in 2005-2006. We studied 650 subjects: 400 newborns and 250
      older individuals (mean age 46.1 y) from Poland and compared results with reports
      from other countries, as well as with the frequency trend of 845G>A HFE across
      South-Eastern European countries using centroid cities. From our 1691G>A FV study
      we identified 626 GG homozygotes, 23 GA heterozygotes, and 1 AA homozygote (n =
      650), giving an A allele frequency of 1.9%, and a summed frequency value for
      Poland of 2.0% (n = 1588); the frequency in Central European countries was 3.9%
      (n = 4559), mostly due to the high value in the Czech Republic: 5.1% (n = 2819);
      the South-Eastern European countries had 2.5% (n = 2410). Among the Eastern
      European countries the 1691G>A FV allele frequency was 1.9% (n=791), between the
      South-Eastern and Eastern European countries there was no significant difference
      (p=0.17). We confirm that the 1691G>A FV allele frequency in Poland, as well as
      other countries compared, is significantly lower than that in Czech.

PMID- 22642592
TI  - Anatomical variations and morphometric study of the optic strut and the anterior
      clinoid process.
AB  - The optic strut and the anterior clinoid process represent bony structures that
      are closely related to anatomically and clinically significant elements such as
      the cavernous sinus, the internal carotid artery, the optic nerve and the
      pituitary gland. The objective of our study was to quantify dimensions of the
      optic strut and anterior clinoid process, and to determine variations in
      positions and forms of these structures. A descriptive anatomical study was
      performed on 200 dry human skulls. We analyzed dimensions and variations in
      position of the optic strut, dimensions of the anterior clinoid process as well
      as the incidence and forms of the caroticoclinoid foramen. The average thickness
      of the optic strut on skulls belonging to males was 3 mm and 2.8 mm on those
      belonging to females. The optic strut was most commonly attached to the anterior
      two fifths on the lower side of the anterior clinoid process. On the male skulls
      the average width of the anterior clinoid process was 9.4 mm (right) and 9.1 mm
      (left). Its length was 9.9 and 9.3 mm. On female skulls the average width of the
      process was 8.7 mm (right) and 8.3 mm (left), while the length measured 9.3 mm on
      the right and 8.9 mm on the opposite side. In our sample, a complete
      caroticoclinoid foramen appeared in 4.25%, a contact form in 2.75%. At last, an
      incomplete form of the foramen was observed in 9.75%. The anatomic variations of
      the investigated structures must be considered during the approaches to the
      cavernous sinus and neurovascular elements of the sellar region.

PMID- 22642593
TI  - TREM-1 is a positive regulator of TNF-alpha and IL-8 production in U937 foam
      cells.
AB  - The purpose of our study was to investigate the expression levels of TREM-1
      (triggering receptor expressed on myeloid cells-1) in U937 foam cells and
      determine whether TREM-1 regulates the production of tumor necrosis factor-alpha
      and interleukin-8 in these cells. Human U937 cells were incubated with phorbol 12
      myristate 13-acetate and then oxidized human low-density lipoprotein to induce
      foam cell formation. Oil red O staining was used to identify the foam cells. The
      production of IL-8 and TNF-alpha by U937 foam cells was assayed by enzyme-linked
      immunosorbent assay. The expression of TREM-1 mRNA in U937 foam cells was
      detected by reverse transcription-polymerase chain reaction. Moreover, U937 foam
      cells were transfected by small interfering RNA using Lipofectamine 2000 to
      knockdown TREM-1. Western blot was performed to assay protein expression of TREM
      1 and ELISA was used to examine the effect of TREM-1 knockdown on IL-8 and TNF
      alpha production. PMA and ox-LDL induced U937 cells to form foam cells. The
      production of TNF-alpha and IL-8 was found to be significantly elevated in U937
      foam cells, concomitant with a significant up-regulation of TREM-1 mRNA. TREM-1
      siRNA was able to partially silence the expression of TREM-1 protein and
      remarkably inhibited TNF-alpha and IL-8 production in U937 foam cells, suggesting
      that TREM-1 is a positive regulator of TNF-alpha and IL-8 production in U937 foam
      cells. Our finding that TREM-1 controls the production of IL-8 and TNF-alpha in
      U937 foam cells defines a potentially critical role of TREM-1 in the pathogenesis
      of atherosclerosis and implicates TREM-1 as a potential therapeutic target for
      the disease.

PMID- 22642594
TI  - Hsp 70, hsCRP and oxidative stress in patients with acute coronary syndromes.
AB  - Acute coronary syndromes (ACS) like unstable angina (UA) and acute myocardial
      infarction (AMI) can lead to the morbidity and mortality. The diagnosis and
      management of patients with ACS in the earliest times after symptom onset are
      considerably important in the emergency service. Study aimed to investigate the
      serum levels of heat shock protein 70 (Hsp 70), high sensitivity C-reactive
      protein (hsCRP), total creatine kinase (CK) activity, creatine kinase MB (CK-MB),
      cardiac troponin I (cTnI), leukocyte count (WBCs) and markers of oxidative stress
      in the first hours of ACS and to view their diagnostic values. 70 patients with
      ACS after admission and 20 sex-matched healthy controls were included in this
      study. Serum Hsp 70, hsCRP, CK, CK-MB, cTnI, protein carbonyls, malondialdehyde
      as well as whole blood WBCs were measured. The level of hsCRP was statistically
      higher in patients with AMI and UA than that of control group (p<0.001). WBCs and
      oxidized protein levels were higher in AMI than in UA and control groups. cTnI
      was related to CK-MB in AMI and UA groups (r=0.731, r=0.806, p<0.001,
      respectively) and also related with hsCRP in UA group (r=0.824, p<0.001). The
      mean Hsp 70 level was higher by 32.2% in AMI and 12.7% in UA patients compared to
      control subjects. hsCRP may have a role in the inflammatory response after ACS.
      In addition to cTnI and CK-MB, WBCs and hsCRP may be useful as a marker for the
      identification of ACS patients with chest pain in early diagnosing.

PMID- 22642595
TI  - Isolation of a potent antibiotic producer bacterium, especially against MRSA,
      from northern region of the Persian Gulf.
AB  - Nowadays, emergence and prevalence of MRSA (Methicillin Resistant Staphylococcus
      aureus) strain have become a great global concern in 21st century, so, it is
      necessary to discover new antibiotics against this pathogen. The aim of this
      study was isolation and evaluation marine bacteria from the Persian Gulf in order
      to finding antibiotic compounds against some pathogenic bacteria. For this
      purpose, water and sediment samples were collected from the Persian Gulf during
      March to October 2009. The antibacterial activity of the isolated bacteria was
      assessed using disc diffusion method. The Growth Curve Interference (GCI)
      parameter against MRSA was determined for the high potential antibiotic producing
      strain. The most important factors affecting fermentation conditions in
      antibiotic production were also optimized. Definite identification of intended
      isolate was confirmed by 16S rRNA sequencing. Altogether, 51 bacterial colony was
      isolated and among them only 3 bacterium showed antibacterial activity.
      Pseudoalteromonas piscicida PG-01 isolated from a sediment sample was chosen as
      the best antibiotic producing strain. This strain was effective against all
      tested Gram-positive bacteria, had good anti-MRSA activity and also GCI value
      against MRSA was two times lower than MIC value. Among the optimized fermentation
      parameters, carbon and nitrogen sources play major role in efficacy of optimized
      antibiotic production. Ultrastructural study on the effect of intended antibiotic
      compounds on MRSA using TEM revealed that the target site for this compound is
      cell wall. Considering the antibacterial effect of PG-01 strain especially
      against MRSA, intended antibiotic compounds can gives hope for treatment of
      diseases caused by multi-drug resistant bacteria.

PMID- 22642596
TI  - Clinical implications of cellular stress responses.
AB  - Cellular stress response is a reaction to changes or fluctuations of
      extracellular conditions that damage the structure and function of
      macromolecules. Different stressors trigger different cellular responses, namely
      induce cell repair mechanisms, induce cell responses that result in temporary
      adaptation to some stressors, induce autophagy or trigger cell death. Inability
      to repair the damage or exposure to prolonged stress may contribute to aging.
      Persistent cell stress often enhances susceptibility to cancer and aging
      associated diseases. Cells and tissues are increasingly being used for
      transplantations and other novel therapeutic methods in which the quality and
      well being of cells is of paramount importance for the treatment to succeed.
      Therefore, discovering the mechanisms of cellular stress responses and the
      ability to detect and ameliorate them is important in prevention of development
      of disorders developed by persistent stress and for the success of
      transplantation and other cell related methods of regenerative medicine.

PMID- 22642597
TI  - Xanthomas of the stomach: a report of two cases.
AB  - Gastrointestinal tract xanthomas are non tumor, well demarcated mucosal lesions
      that consist of foamy histiocytes, most commonly diagnosed in the stomach. The
      histologic appearance of xanthomas can resemble certain malignant lesions. After
      retrospective data base search, we have encountered only 2 cases of xanthomas,
      both in the antral part of the stomach. Lamina propria of the mucosa contained
      rare, chronic inflammatory infiltrate and clusters of oval and polygonal cells
      with abundant, foamy cytoplasm. The cytoplasm of described cells did not show the
      presence of mucin (Periodic acid-Schiff (PAS) and Alcian blue staining). The
      cells showed distinct cytoplasmic CD68 positivity and CKMNF116 negativity, which
      confirmed the diagnosis of xanthoma. Given the frequent association of xanthomas
      and known precancerous lesions of gastric mucosa, and occasional coexistence of
      malignant change, we need to pay attention to its diagnosis, and it is advisable
      to use both histochemical and immunohistochemical methods.

PMID- 22642598
TI  - General anaesthesia in an adult patient with Morquio syndrom with emphasis on
      airway issues.
AB  - Patients with Morquio syndrome possess a number of characteristics which may
      complicate an anaesthetic procedure. The most important is that a deposition of
      mucopolysaccharides in the soft tissues of the oro-pharynx distorts the airway,
      making the airway management difficult, while the atlanto-axial instability puts
      these patients at risk of subluxation and quadriparesis. As the endotracheal
      intubation in Morquio syndrome patients may be difficult or even impossible, we
      recommend the technique of awake fiberoptic intubation to be considered. Our
      approach to awake fiberoptic intubation in an adult patient is described in this
      case report.

PMID- 22642599
TI  - Prostatic carcinoma bilateral iris metastases.
AB  - We described a patient with bilateral iris metastases resulted from prostatic
      cancer. Slit lamp and ultrasonography examination of the both eye demonstrated
      tumor of the iris, as an amelanotic vascular mass located on the superior
      temporal quadrant. On open biopsy revealed undifferentiated tissue that stained
      strongly positive for prostate carcinoma, confirming the diagnosis of metastasis
      prostate adenocarcinoma. Early diagnostic procedures are essential for the causal
      therapy of prostate carcinoma as the primary neoplasm.

PMID- 22642600
TI  - Researching chemicals in human milk can be conducted without discouraging
      breastfeeding.

PMID- 22642601
TI  - Establishment of mesenchymal cell line derived from human developing odontoma.
AB  - OBJECTIVES: An odontoma, which shows proliferating odontogenic epithelium and
      mesenchymal tissue, is one of the most common odontogenic tumors encountered.
      These are commonly found in tooth-bearing regions, although the etiology remains
      unknown. There are no previous reports of an established line of immortalized
      human odontoma cells. METHODS: Using odontoma fragments obtained from a girl
      treated at our department, we established an immortalized human odontoma cell
      line and investigated cell morphology, dynamic proliferation, the presence of
      contamination, and karyotype. Moreover, cell characterization was examined using
      osteogenic and odontogenic markers. RESULTS: We successfully established a
      mesenchymal odontoma cell (mOd cells). The cells were found to be fibroblastic
      and had a high level of telomerase activity. Cell growth was confirmed after more
      than 200 population doublings without significant growth retardation. mOd cells
      expressed mRNA for differentiation markers, including collagen type I (COLI),
      alkaline phosphatase, bone sialoprotein, osteopontin, osteocalcin, cementum
      derived protein (CP-23), dentin sialophosphoprotein (DSPP), and distal-less
      homeobox 3 (DLX3), as well as bone morphogenetic proteins (BMPs). In addition,
      they showed a high level of calcified nodule formation activity in vitro.
      CONCLUSIONS: We successfully established a cell line that may be useful for
      investigating the mechanisms of normal odontogenesis as well as characteristics
      of odontoma tumors.

PMID- 22642602
TI  - The hypoxic microenvironment upgrades stem-like properties of ovarian cancer
      cells.
AB  - BACKGROUND: To study whether hypoxia influences the stem-like properties of
      ovarian cancer cells and their biological behavior under hypoxia. METHOD: Ovarian
      cancer cell lines ES-2 and OVCAR-3 were cultivated in different oxygen tensions
      for proliferation, cell cycling and invasion analyses. The clonogenic potential
      of cells was examined by colony formation and sphere formation assays. Stem cell
      surface markers, SP and CD44bright and CD44dim cells were analyzed by flow
      cytometry. Protein expression of HIF-1alpha, HIF-2alpha, Ot3/4 and Sox2 were
      investigated by Western blotting. RESULTS: Both cell lines cultivated at hypoxic
      condition grew relatively slowly with extended G0/G1 phase. However, if the cells
      were pre-treated under 1% O2 for 48 hrs before brought back to normoxia, the
      cells showed significantly higher proliferation rate with higher infiltration
      capability, and significant more colonies and spheres, in comparison to the cells
      always cultivated under normoxia. CD44bright cells expressed significantly higher
      levels of Oct3/4 and Sox2 than the CD44dim cells and formed significantly more
      clones and spheres examined in vitro. Hypoxic treatment of the cells resulted in
      stronger CD44 expression in both cell lines, and stronger CD133 expression in the
      OVCAR-3 cell line. In parallel with these findings, significantly increased
      number of side population (SP) cells and up-regulated expression of Oct3/4 and
      Sox2 in both ES-2 and OVCAR-3 cell lines were observed. CONCLUSION: We conclude
      that ovarian cancer cells survive hypoxia by upgrading their stem-like properties
      through up-regulation of stemness-related factors and behave more aggressively
      when brought back to higher oxygen environment.

PMID- 22642603
TI  - Beta cell function and BMI in ethnically diverse children with newly diagnosed
      autoimmune type 1 diabetes.
AB  - OBJECTIVE: To examine the relationship between BMI and beta-cell function at
      diagnosis of autoimmune type 1 diabetes (T1D) in a large group of ethnically
      diverse children. METHODS: Cross-sectional analysis of 524 children (60.8% White,
      19.5% Hispanic, 14.5% African-American, 5.2% other non-Hispanic; mean age = 9.8
      yr [SD = 2.5]) with newly diagnosed autoimmune T1D. RESULTS: As much as 22.2% of
      children were overweight or obese. Median random serum C-peptide was 0.40 ng/mL
      (25th-75th percentiles = 0.3-0.8), with median glycemia of 366 mg/dL (25th-75th
      percentiles = 271-505). Median C-peptide was 0.3, 0.5, 0.7, and 0.85 ng/mL,
      respectively, in underweight, normal weight, overweight, and obese children (p <
      0.0001, Kruskal-Wallis). In the final model (p < 0.0001), the odds of having
      preserved C-peptide (>=0.6 ng/mL) were increased by 2.4-fold (95% CI = 1.2-4.9, p
      < 0.015) and 4.1-fold (1.9-8.5, p < 0.0001), respectively, in overweight and
      obese compared to lean children; 1.3-fold per each year of age; 2.5-fold in girls
      compared to boys; 4-fold in children who presented without, compared to with,
      diabetes ketoacidosis (DKA); and decreased by 21% for each point increase in
      HbA1c. Tanner stage, race/ethnicity, glycemia, and number of anti-islet
      antibodies expressed were not independently associated with preserved C-peptide.
      The association between BMI and C-peptide levels was significant in children with
      and without preserved C-peptide. Excluding patients who presented with DKA and/or
      using BMI obtained 5 wk after diagnosis did not alter the results. CONCLUSION:
      Obese and overweight children compared to lean children have greater beta-cell
      function at the onset of autoimmune T1D. Prospective studies on the relationships
      among BMI, beta-cell function, and progression to clinical T1D are warranted.

PMID- 22642604
TI  - Ionic concentration effects on reverse micelle size and stability: implications
      for the synthesis of nanoparticles.
AB  - We present a systematic investigation and analysis of the structure and stability
      of reverse micelle systems with the addition of NH(4)OH, ZrOCl(2), and
      Al(NO(3))(3) salts. We demonstrate that the reverse micelle size decreases with
      increasing salt additions until one reaches a critical concentration, which
      characterizes the onset of system destabilization. The concept of an electrical
      double layer, as it applies to reverse micelles, is considered for explaining
      features of destabilization, including the initial decrease in reverse micelle
      size, the destabilization concentration, and the effect of cation valence. We
      propose that the reduction in size prior to instability is caused by compression
      of the reverse micelle electrical double layers, as higher concentrations of
      salts are present. The reduced thickness of the electrical double layers allows
      the decaying potentials to move into closer proximity to each other before
      generating enough repulsion to balance the forces for reverse micelle formation
      and form a new equilibrium average reverse micelle size. The point of reverse
      micelle instability has been related to the formation of a two-phase system as a
      result of the inability to further compress the salt co-ions in the core of the
      reverse micelles, which would cause an excessive repulsive force between the
      overlapping potentials. We have extracted a critical potential of -89 nV between
      the two overlapping potentials for the AOT/water/isooctane (omega(0) = 10)
      systems studied. All these effects have important implications for the
      preparation of nanopowders by reverse micelle synthesis. If the reverse micelles
      are unstable before the precipitates are formed, then the advantage of reverse
      micelle synthesis is immediately lost.

PMID- 22642605
TI  - Bio-psycho-social assessment of occlusal dysaesthesia patients.
AB  - Dentists occasionally experience occlusal dysaesthesia (OD) patients, who
      complain of bite discomfort without evident occlusal abnormalities. It is
      suggested that this condition is related to somatosensory abnormalities of the
      trigeminal system and/or psychological problems such as somatoform disorders. The
      aim of this study was to investigate the characteristics of OD with a bio-psycho
      social approach. Twelve OD patients (10 women, two men; mean age 54.7 years) and
      twelve healthy volunteers (10 women, two men; mean age 54.8 years) were selected.
      They were assessed using (i) interdental thickness discrimination ability test
      using 2-, 5- and 10-mm-thick standard blocks and 12 test blocks that were thinner
      or thicker than the corresponding standard block and (ii) psychological tests:
      General Health Questionnaire (GHQ60) and Profile of Mood States (POMS) brief
      form. There was no significant difference in the interdental thickness
      discrimination ability between OD patients and controls (mixed-model anova,
      P=1.000). Regarding psychological tests, there were no significant differences
      between OD patients and controls in the total scores for either GHQ60 (P=0.143)
      or POMS brief-form (P=0.319) (Wilcoxon's test). However, OD patients showed
      significant differences from controls in several subscales, that is, 'somatic
      symptoms' (P=0.039) and 'severe depression' (P=0.039) for GHQ60 and 'depression
      dejection' (P=0.014) and 'vigour' (P=0.008) for POMS brief-form (Wilcoxon's
      test). These results suggest there is no difference in interdental thickness
      discrimination ability between OD patients and normal controls, but OD patients
      tend to score higher on psychosomatic distress.

PMID- 22642607
TI  - Low-level laser therapy for pain relief after episiotomy: a double-blind
      randomised clinical trial.
AB  - AIMS AND OBJECTIVES: To evaluate the effectiveness of a low-level laser therapy
      for pain relief in the perineum following episiotomy during childbirth.
      BACKGROUND: Laser irradiation is a painless and non-invasive therapy for perineal
      pain treatment and its effects have been investigated in several studies, with no
      clear conclusion on its effectiveness. DESIGN: A double-blind randomised
      controlled clinical trial. METHOD: One hundred and fourteen women who underwent
      right mediolateral episiotomies during vaginal birth in an in-hospital birthing
      centre in Sao Paulo, Brazil and reported pain >= 3 on a numeric scale (0-10) were
      randomised into three groups of 38 women each: two experimental groups (treated
      with red and infrared laser) and a control group. The experimental groups were
      treated with laser applied at three points directly on the episiotomy after
      suturing in a single session between 6-56 hours postpartum. We used a diode laser
      with wavelengths of 660 nm (red laser) and 780 nm (infrared laser). The control
      group participants underwent all laser procedures, excluding the emission of
      irradiation. The participants and the pain scores evaluator were blinded to the
      type of intervention. The perineal pain scores were assessed at three time
      points: before, immediately after and 30 minutes after low-level laser therapy.
      RESULTS: The comparison of perineal pain between the three groups showed no
      significant differences in the three evaluations (p = 0.445), indicating that the
      results obtained in the groups treated with low-level laser therapy were
      equivalent to the control group. CONCLUSIONS: Low-level laser therapy did not
      decrease the intensity of perineal pain reported by women who underwent right
      mediolateral episiotomy. RELEVANCE TO CLINICAL PRACTICE: The effect of laser in
      perineal pain relief was not demonstrated in this study. The dosage may not have
      been sufficient to provide relief from perineal pain after episiotomy during a
      vaginal birth.

PMID- 22642608
TI  - Polymorphisms in the interleukin-6 receptor gene (Asp358Ala) and body mass index
      in Chilean women with type 1 diabetes.
AB  - INTRODUCTION: Interleukin-6 receptor (IL6R) has been linked with type 2 diabetes
      and obesity. The presence of the Asp allele in Asp358Ala of IL6R has been linked
      with insulin resistance and weight gain. AIM: The aim of this study is to
      evaluate the frequency and the association of the Asp358Ala in the IL6R gene in
      Chilean women with type 1 diabetes (T1D) and its relationship with body mass
      index (BMI). PATIENTS AND METHODS: One hundred and forty-five patients with T1D
      (N = 145) and healthy control women (N = 103) were recruited. The polymorphisms
      were studied with polymerase chain reaction and restriction fragment length
      polymorphisms. The effect of the polymorphisms on BMI and age of diagnosis was
      evaluated. RESULTS: A higher frequency of the Asp allele was observed in patients
      with T1D compared with controls (0.483 vs. 0.364; p < 0.01). The Asp358Asp
      genotype was more prevalent in the T1D group compared with controls (0.152 vs.
      0.097; p < 0.01). T1D patients younger than 19 years had a positive association
      of BMI-standard deviation scores with the Asp allele (p < 0.05). Finally, lower
      Glycated Hemoglobin 1c (HbA1c) levels were observed in patients carrying the Asp
      allele (p < 0.01). CONCLUSIONS: T1D in Chilean women appears to be associated
      with the presence of the Asp allele in IL6R. The IL6R polymorphism (Asp358/Asp)
      was associated with BMI in T1D patients. This genetic variant could have some
      role in weight gain in T1D women.

PMID- 22642609
TI  - Cyclic heptapeptides, cordyheptapeptides C-E, from the marine-derived fungus
      Acremonium persicinum SCSIO 115 and their cytotoxic activities.
AB  - Three new cycloheptapeptides, cordyheptapeptides C-E (1-3), were isolated from
      the fermentation extract of the marine-derived fungus Acremonium persicinum SCSIO
      115. Their planar structures were elucidated on the basis of extensive MS, as
      well as 1D and 2D (COSY, HMQC, and HMBC) NMR spectroscopic data analyses. The
      absolute configurations of the amino acid residues were determined by single
      crystal X-ray diffraction, Marfey's method, and chiral-phase HPLC analysis.
      Compounds 1 and 3 displayed cytotoxicity against SF-268, MCF-7, and NCI-H460
      tumor cell lines with IC(50) values ranging from 2.5 to 12.1 MUM.

PMID- 22642610
TI  - Walking away from type 2 diabetes: trial protocol of a cluster randomised
      controlled trial evaluating a structured education programme in those at high
      risk of developing type 2 diabetes.
AB  - BACKGROUND: The prevention of type 2 diabetes is a recognised health care
      priority globally. Within the United Kingdom, there is a lack of research
      investigating optimal methods of translating diabetes prevention programmes,
      based on the promotion of a healthy lifestyle, into routine primary care. This
      study aims to establish the behavioural and clinical effectiveness of a
      structured educational programme designed to target perceptions and knowledge of
      diabetes risk and promote a healthily lifestyle, particularly increased walking
      activity, in a multi-ethnic population at a high risk of developing type 2
      diabetes. DESIGN: Cluster randomised controlled trial undertaken at the level of
      primary care practices. Follow-up will be conducted at 12, 24 and 36 months. The
      primary outcome is change in objectively measured ambulatory activity. Secondary
      outcomes include progression to type 2 diabetes, biochemical variables (including
      fasting glucose, 2-h glucose, HbA1c and lipids), anthropometric variables,
      quality of life and depression. METHODS: 10 primary care practices will be
      recruited to the study (5 intervention, 5 control). Within each practice,
      individuals at high risk of impaired glucose regulation will be identified using
      an automated version of the Leicester Risk Assessment tool. Individuals scoring
      within the 90th percentile in each practice will be invited to take part in the
      study. Practices will be assigned to either the control group (advice leaflet) or
      the intervention group, in which participants will be invited to attend a 3 hour
      structured educational programme designed to promote physical activity and a
      healthy lifestyle. Participants in the intervention practices will also be
      invited to attend annual group-based maintenance workshops and will receive
      telephone contact halfway between annual sessions. The study will run from 2010
      2014. DISCUSSION: This study will provide new evidence surrounding the long-term
      effectiveness of a diabetes prevention programme run within routine primary care
      in the United Kingdom. TRIAL REGISTRATION: ClinicalTrials.Gov identifier:
      NCT00941954.

PMID- 22642611
TI  - Good interobserver and intraobserver agreement in the evaluation of the new ILAE
      classification of focal cortical dysplasias.
AB  - PURPOSE: An International League Against Epilepsy (ILAE) consensus classification
      system for focal cortical dysplasias (FCDs) has been published in 2011 specifying
      clinicopathologic FCD variants. The aim of the present work was to
      microscopically assess interobserver agreement and intraobserver reproducibility
      for FCD categories among an international group of neuropathologists with
      different levels of experience and access to epilepsy surgery tissue. METHODS:
      Surgical FCD specimens covering a broad histopathology spectrum were retrieved
      from 22 patients with epilepsy. Three surgical nonepilepsy specimens served as
      controls. A total of 188 slides with routine or immunohistochemical stainings
      were digitalized with a slide scanner to allow Internet-based microscopy review.
      Nine experienced neuropathologists were invited to review these cases twice at a
      time gap of 3 months and different orders of case presentation. The 2011 ILAE FCD
      consensus classification served as instruction. Kappa analysis was calculated to
      estimate interobserver and intraobserver agreement levels. In a third evaluation
      round, 21 additional neuropathologists with different experience and access to
      epilepsy surgery reviewed the same case series. KEY FINDINGS: Interobserver
      agreement was good (kappa = 0.6360), with 84% consensus of diagnoses during the
      first evaluation (21 of 25 cases). Kappa values increased to 0.6532 after
      reevaluation, and consensus was obtained in 24 (96%) of 25 cases. Overall
      intraobserver reproducibility was also good (kappa = 0.7824, ranging from 0.4991
      to 1.000). Fewest changes in the classification were made in the FCD type II
      group (2.2% of 225 original diagnoses), whereas the majority of changes occurred
      in FCD type III (13.7% of 225 original diagnoses). In the third evaluation round,
      interobserver agreement was reflected by the level of experience of each
      neuropathologist, with kappa values ranging from moderate (0.5056; high level of
      experience >40 cases/year) to low (0.3265; low level of experience <10
      cases/year). SIGNIFICANCE: Our study achieved a good and reliable interobserver
      agreement among the group of expert neuropathologists originally involved in the
      ILAE FCD consensus classification system. Intraobserver reproducibility in this
      group was even more robust. These results showed considerable improvement
      compared to a previous study evaluating the 2004 Palmini FCD classification.
      Agreement levels were lower in our second group of neuropathologists and were
      related to their level of access and experience with epilepsy surgery specimens.
      These results suggested that the more precise ILAE definition of FCD
      histopathology patterns improves operational procedures in the diagnosis of FCDs.
      On the other hand, microscopic assessment of FCD is a challenge and requires
      sustained experience and teaching. The virtual slide review system allowed
      testing of this hypothesis and reached a widespread group of participating
      colleagues from different centers all over the world. We propose to further use
      this tool as a teaching device and also to address other epilepsy-associated
      entities still difficult to classify such as hippocampal sclerosis, long-term
      epilepsy-associated tumors, or mild malformations of cortical development
      (mMCDs), which were not yet covered by current ILAE classification systems.

PMID- 22642612
TI  - Prevalence and profile of sleep disturbances in Guillain-Barre Syndrome: a
      prospective questionnaire-based study during 10 days of hospitalization.
AB  - INTRODUCTION: Sleep disturbances in Guillain-Barre Syndrome (GBS), though common,
      have not received focused attention. OBJECTIVES: To study frequency and nature of
      sleep disturbances in patients with GBS, using validated questionnaires, and
      analyze the contributing factors. MATERIALS AND METHODS: This prospective study
      included 60 patients fulfilling National Institute of Neurological and
      Communicative Diseases and Stroke (NINCDS) criteria for GBS (mean age: 32.7 +/-
      12.9 years; median: 30 years; M:F = 46:14), evaluated from 2008 to 2010. Data
      regarding sleep were collected on 10 consecutive days following admission using
      Richard Campbell Sleep score, St Mary's Hospital Sleep Questionnaire, and
      Pittsburgh Sleep Quality Index (PSQI) and correlated with various possible
      contributing factors like pain, paresthesia, anxiety, depression, autonomic
      dysfunctions, severity of disease, and therapeutic interventions among others.
      OBSERVATIONS: Qualitative and quantitative sleep disturbances were rather
      frequent and involved over 50% patients: abnormal PSQI - 13.3%, abnormal score on
      Richard scale - 51.6%, abnormal sleep onset latency - 35%, sleep fragmentation -
      40%, and reduced sleep duration - 46.6%. The symptoms were severe during the
      first week of hospitalization and reduced thereafter. Sleep disturbances as
      scored on Richard scale significantly correlated with anxiety, pain, paresthesia,
      and severity of immobility (P < 0.05) but not with depression and use of
      analgesics or antineuritic drugs. CONCLUSIONS: This study first of its kind
      suggests that sleep disturbance in GBS is frequent, multi-factorial, often
      disturbing, and varies during the course of illness. Routine enquiry into the
      sleep disturbances and timely intervention may reduce morbidity and improve their
      quality of life.

PMID- 22642613
TI  - Optimal surveillance and eradication of invasive species in heterogeneous
      landscapes.
AB  - Cost-effective surveillance strategies are needed for efficient responses to
      biological invasions and must account for the trade-offs between surveillance
      effort and management costs. Less surveillance may allow greater population
      growth and spread prior to detection, thereby increasing the costs of damages and
      control. In addition, surveillance strategies are usually applied in environments
      under continual invasion pressure where the number, size and location of
      established populations are unknown prior to detection. We develop a novel
      modeling framework that accounts for these features of the decision and invasion
      environment and determines the long term sampling effort that minimises the total
      expected costs of new invasions. The optimal solution depends on population
      establishment and growth rates, sample sensitivity, and sample, eradication, and
      damage costs. We demonstrate how to optimise surveillance systems under budgetary
      constraints and find that accounting for spatial heterogeneity in sampling costs
      and establishment rates can greatly reduce management costs.

PMID- 22642615
TI  - Tongue pressure production while swallowing water and pudding and during dry
      swallow using a sensor sheet system.
AB  - The tongue assumes an important role in bolus formation and transportation to the
      oropharynx and in retaining pharyngeal pressure during mastication and
      swallowing. Although the state of tongue-palate contact during swallowing is
      thought to change with bolus type, the details of these changes have yet to be
      clarified under normal physiological conditions. The purpose of this study was to
      examine the effect of bolus type on tongue pressure production against the hard
      palate during swallowing. Tongue pressures during swallowing 10 mL of water and
      10 g of pudding and during dry swallow were measured with a sensor sheet system
      with five measurement points to evaluate normal physiological swallowing in 10
      healthy dentate individuals. There was a common pattern in the sequential order
      of tongue pressure generation among the three swallowing conditions: tongue
      pressure was generated significantly earlier at the anterior-median part,
      followed by the posterior parts. During swallowing pudding and dry swallow, the
      duration of tongue pressure tended to increase at all channels except for the
      posterior-median part. The maximal magnitude of tongue pressure was significantly
      higher when swallowing pudding than when swallowing water at all channels except
      for the posterior-median part. The integrated value of tongue pressure was
      significantly higher when swallowing pudding than when swallowing water at all
      channels except for the posterior-median part. From these results, it was
      considered the tongue changed the sequential order, the duration and the
      magnitude of tongue pressure production according to the swallowing conditions
      (liquid swallowing, semisolid swallowing, dry swallow).

PMID- 22642614
TI  - Measuring the quality of MDT working: an observational approach.
AB  - BACKGROUND: Cancer multidisciplinary teams (MDTs) are established in many
      countries but little is known about how well they function. A core activity is
      regular MDT meetings (MDMs) where treatment recommendations are agreed. A mixed
      methods descriptive study was conducted to develop and test quality criteria for
      observational assessment of MDM performance calibrated against consensus from
      over 2000 MDT members about the "characteristics of an effective MDT". METHODS:
      Eighteen of the 86 'Characteristics of Effective MDTs' were considered relevant
      and feasible to observe. They collated to 15 aspects of MDT working covering four
      domains: the team (e.g. attendance, chairing, teamworking); infrastructure for
      meetings (venue, equipment); meeting organisation and logistics; and patient
      centred clinical decision-making (patient-centredness, clarity of
      recommendations). Criteria for rating each characteristic from 'very poor' to
      'very good' were derived from literature review, observing MDMs and expert input.
      Criteria were applied to 10 bowel cancer MDTs to assess acceptability and measure
      variation between and within teams. Feasibility and inter-rater reliability was
      assessed by comparing three observers. RESULTS: Observational assessment was
      acceptable to teams and feasible to implement. Total scores from 29 to 50 (out of
      58) highlighted wide diversity in quality between teams. Eight teams were rated
      either 'very good/good' or 'very poor/poor' for at least three domains
      demonstrating some internal consistency. 'Very good' ratings were most likely for
      attendance and administrative preparation, and least likely for patient
      centredness of decision-making and prioritisation of complex cases. All except
      two characteristics had intra-class correlations of >=0.50. CONCLUSIONS: This
      observational tool (MDT-OARS) may contribute to the assessment of MDT
      performance. Further testing to confirm validity and reliability is required.

PMID- 22642616
TI  - Periventricular nodular heterotopia functionally couples with the overlying
      hippocampus.
AB  - Patients with periventricular nodular heterotopia (PVNH) often have severe
      epilepsy. However, it is unclear how the heterotopia contributes to
      epileptogenesis. Recently, electrophysiologic studies using intraoperative depth
      electrodes have indicated that interaction between the heterotopia and overlying
      cortex is crucial for seizure onset. We performed an in vitro physiologic study
      using slices of resected brain from a 22-year-old man with PVNH, who manifested
      medically refractory mesial temporal lobe epilepsy. Preoperative evaluation
      indicated that the right mesial temporal structure and PVNH were the
      epileptogenic focus. The resected tissue was immediately immersed in cold
      artificial cerebrospinal fluid, and then slices of the brain tissue including the
      heterotopic nodules and overlying hippocampus were prepared. We electrically
      stimulated the incubated slices, and the elicited neural activities were analyzed
      as changes in the flavoprotein fluorescence signals. When we stimulated either
      the heterotopic nodule or the overlying hippocampus, clear functional coupling of
      neural activities between these structures was observed. The coupling response
      evoked by stimulation of the subiculum and developing within the heterotopic
      nodule was enhanced by application of bicuculline. Therefore, activities of the
      hippocampus and the nodule are closely correlated.

PMID- 22642618
TI  - Nurse-physician communication concerning artificial nutrition or hydration (ANH)
      in patients with dementia: a qualitative study.
AB  - AIMS AND OBJECTIVES: To explore nurses' experiences with nurse-physician
      communication during artificial nutrition or hydration (ANH) decision-making in
      hospitalised patients with dementia. BACKGROUND: Artificial nutrition or
      hydration decision-making often occurs in patients with dementia. Effective
      communication between professionals is extremely challenging in this population,
      because these patients are unable to communicate their treatment wishes. DESIGN:
      Qualitative interview design. METHODS: Between April 2008 and June 2009, we
      conducted 21 interviews with nurses from nine different hospitals geographically
      spread throughout Flanders (Belgium). Interviews were audiotaped and later
      transcribed. Data processing involved (1) simultaneous and systematic data
      collection and analysis, (2) constant forwards-backwards wave, (3) continuous
      dialogue with the data and (4) interactive team processes. RESULTS: The
      interviews showed that communication with physicians is the central instrument
      the nurses used in their attempts to realise their perception of 'the best
      possible care'. From the nurses' perspective, we distinguished three mutually
      connected factors that affected the effectiveness of nurse-physician
      communication during artificial nutrition or hydration decision-making: the
      physicians' attitude towards the nurses, the nurses' attitude towards the
      physicians and the forms of communication used by the nurses. The complex
      interaction between these three factors resulted in a range of nurses'
      perceptions, varying from positive to negative. The direction of their
      perceptions depended on the extent to which they succeeded or failed to use nurse
      physician communication as an instrument to realise the 'best care'. CONCLUSION:
      Nurse-physician communication was the most important instrument determining
      whether nurses succeeded or failed to actively act as a patient's representative
      and whether nurses achieved the best possible care in co-operation with
      physicians. RELEVANCE TO CLINICAL PRACTICE: To reach optimal care and nurse job
      satisfaction, nurse-physician communication during artificial nutrition or
      hydration decision-making should be an open dialogue characterised by mutual
      respect and understanding.

PMID- 22642619
TI  - Determination of the concentration and the average number of gold atoms in a gold
      nanoparticle by osmotic pressure.
AB  - For an ideal solution, an analytical expression for the macromolecule
      concentration, electrolyte concentration, and solution osmotic pressure is
      obtained on the basis of the van't Hoff equation and the Donnan equilibrium. The
      expression was further applied to a colloid solution of about 3 nm glutathione
      stabilized gold nanoparticles. The concentration of the colloid solution and the
      average net ion charge number for each gold nanoparticle were determined with the
      measured osmotic pressure data. Meanwhile, the gold contents of the solutions
      were analyzed by means of atomic absorption spectrophotometry, and the results
      were combined with the determined concentration of gold nanoparticle colloids to
      determine that the average number of gold atoms per 3 nm gold nanoparticle is
      479, which is 1/1.7 times the number of atoms in bulk metallic gold of the same
      size. The same proportion also occurred in the 2 nm 4-mercaptobenzoic acid
      monolayer-protected gold nanoparticles prepared by Ackerson et al., who utilized
      the quantitative high-angle annular dark-field scanning transmission electron
      microscope to determine the average number of gold atoms per nanoparticle
      (Ackerson, C. J.; Jadzinsky, P. D.; Sexton J. Z.; Bushnell, D. A.; Kornberg, R.
      D. Synthesis and Bioconjugation of 2 and 3 nm-Diameter Gold Nanoparticles.
      Bioconjugate Chem. 2010, 21, 214-218).

PMID- 22642617
TI  - Medical student attitudes towards family medicine in Spain: a statewide analysis.
AB  - BACKGROUND: Family and community medicine (FM) became a recognized specialty in
      Spain in 1978; however, most medical schools in Spain still lack mandatory core
      courses in FM. In order to explore the perceptions, expectations and level of
      information amongst medical students in Spain in relation to FM and PC, and the
      training in these areas in the curriculum of the Medical Schools, a survey was
      developed to be administered in medical schools every two years. This article
      presents data from the first questionnaire administration. METHODS: The study
      population was all first-, third-, and fifth-year students (2009-2010) in 22
      participating medical schools in Spain (of 27 total). The 83-item survey had
      three sections: personal data, FM training, professional practice expectations,
      and preferences). Chi-squared test or analyses of variance were used, as
      appropriate. RESULTS: We had a 41.8% response rate (n = 5299/12924); 89.8%
      considered the social role of FM to be essential, while only 20% believed the
      specialty was well respected within the medical profession. The appeal of FM
      increased with years of study, independent of student characteristics or medical
      school attended. Among third and fifth-year students, 54.6% said their specialty
      preferences had changed during medical school; 73.6% felt that FM specialists
      should teach FM courses, and 83.3% thought that FM rotations in primary care
      centres were useful. CONCLUSIONS: Students valued the social role of FM more
      highly than its scientific standing. The vast majority believe that FM training
      should be mandatory. Only 25% of first-year students have clear preferences for a
      specialization. Interest in FM increases moderately over their years of study.
      Working conditions in FM have decisive influence in choosing a specialty.

PMID- 22642620
TI  - Disclosing doubtful indications for emergency cesarean sections in rural
      hospitals in Tanzania: a retrospective criterion-based audit.
AB  - OBJECTIVE: To investigate in depth to what extent indications for emergency
      cesarean sections followed evidence-based audit criteria for realistic best
      practice. DESIGN: A quality assurance analysis based on a retrospective criterion
      based audit. SETTING: Two rural hospitals in Tanzania. POPULATION: From 2009, 400
      cesarean section instances were investigated. Of these, 303 were emergency
      cesarean sections and therefore included. METHODS: Documented indications for and
      management preceding the emergency cesarean sections were compared with the audit
      criteria. MAIN OUTCOME MEASURES: Prevalence of suboptimal care. RESULTS: Of the
      emergency sections, 26% appeared to be decided based on inappropriate
      indications, and in an additional 38%, the indications were unclear. Prolonged
      labor was the leading indication; in 36% of these, labor progressed timely and/or
      the membranes were still intact. In 26%, previous cesarean section was the
      indication, half of these with one previous section only. Fetal distress was an
      indication in 14%, but for 84% of these the fetal heart rate was either
      reassuring or not documented. For nine women, section was decided upon because of
      intrauterine fetal death; none had a trial of forceps/vacuum extraction or
      destructive surgery. CONCLUSION: A considerable number of the audited emergency
      cesarean sections were performed on doubtful indications. In the light of the
      rising trend in global cesarean section rates, there seems to be a need to ensure
      quality of management preceding cesarean sections. This is particularly called
      for in rural sub-Saharan Africa where cesarean rates are still low and health
      risks of emergency surgery not negligible.

PMID- 22642621
TI  - A trait-based approach for modelling microbial litter decomposition.
AB  - Trait-based models are an emerging tool in ecology with the potential to link
      community dynamics, environmental responses and ecosystem processes. These models
      represent complex communities by defining taxa with trait combinations derived
      from prior distributions that may be constrained by trade-offs. Herein I develop
      a model that links microbial community composition with physiological and
      enzymatic traits to predict litter decomposition rates. This approach allows for
      trade-offs among traits that represent alternative microbial strategies for
      resource acquisition. The model predicts that optimal strategies depend on the
      level of enzyme production in the whole community, which determines resource
      availability and decomposition rates. There is also evidence for facilitation and
      competition among microbial taxa that co-occur on decomposing litter. These
      interactions vary with community investment in extracellular enzyme production
      and the magnitude of trade-offs affecting enzyme biochemical traits. The model
      accounted for 69% of the variation in decomposition rates of 15 Hawaiian litter
      types and up to 26% of the variation in enzyme activities. By explicitly
      representing diversity, trait-based models can predict ecosystem processes based
      on functional trait distributions in a community. The model developed herein
      illustrates that traits influencing microbial enzyme production are some of the
      key controls on litter decomposition rates.

PMID- 22642623
TI  - Ochratoxin A exposure biomarkers in the Czech Republic and comparison with
      foreign countries.
AB  - Among ochratoxins, ochratoxin A (OTA) occupies a dominant place and represents
      significant risk for human and animal health which also implies economic losses
      around the world. OTA is nephrotoxic, hepatotoxic, teratogenic and immunotoxic
      mycotoxin. OTA exposure may lead to formation of DNA adducts resulting to
      genotoxicity and carcinogenicity (human carcinogen of 2B group). Now it seems
      that OTA could be "a complete carcinogen" which obliges to monitor its presence
      in biological materials, especially using the suitable biomarkers. In this
      article, OTA findings in urine, blood, serum, plasma and human kidneys (target
      dose) in the Czech Republic and comparison with foreign countries are presented.

PMID- 22642622
TI  - NF-kappaB2 mutation targets survival, proliferation and differentiation pathways
      in the pathogenesis of plasma cell tumors.
AB  - BACKGROUND: Abnormal NF-kappaB2 activation has been implicated in the
      pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal
      role for aberrant NF-kappaB2 signaling in the development of plasma cell tumors
      has not been established. Also unclear is the molecular mechanism that drives the
      tumorigenic process. We investigated these questions by using a transgenic mouse
      model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF
      kappaB2 mutant, and human multiple myeloma cell lines. METHODS: We conducted a
      detailed histopathological characterization of lymphomas developed in p80HT
      transgenic mice and microarray gene expression profiling of p80HT B cells with
      the goal of identifying genes that drive plasma cell tumor development. We
      further verified the significance of our findings in human multiple myeloma cell
      lines. RESULTS: Approximately 40% of p80HT mice showed elevated levels of
      monoclonal immunoglobulin (M-protein) in the serum and developed plasma cell
      tumors. Some of these mice displayed key features of human multiple myeloma with
      accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or
      diffuse osteoporosis. Gene expression profiling of B cells from M-protein
      positive p80HT mice revealed aberrant expression of genes known to be important
      in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1,
      survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3,
      a key downstream component of IL-10 signaling, in the survival of human multiple
      myeloma cells. CONCLUSIONS: These findings provide a mouse model for human
      multiple myeloma with aberrant NF-kappaB2 activation and suggest a molecular
      mechanism for NF-kappaB2 signaling in the pathogenesis of plasma cell tumors by
      coordinated regulation of plasma cell generation, proliferation and survival.

PMID- 22642624
TI  - Utility of the gagging problem assessment questionnaire in assessing patient
      sensitivity to dental treatments.
AB  - Although the Gagging Problem Assessment Questionnaire (GPA) can be used to
      identify patients with gag reflex, it does not provide information about patient
      sensitivity to dental procedures. The aim of this study was to assess the utility
      of GPA in determining patient sensitivity (i.e. gag reflex) in response to intra
      oral radiography and impression-taking procedures. The study included 95 patients
      (65 women; mean age, 44.2 +/- 13.4 years) undergoing dental treatment at a
      Turkish dental school. Patients completed the patient section of the GPA before
      their dental examination. An observing dentist monitored and scored the gag
      reflex of patients during each step of intra-oral radiographic examination and
      impression taking. The overall sensitivity of the patient to the entire process
      was also recorded. Descriptive statistics, one-way analysis of variance and the
      Tukey's test were used for statistical analysis. Patients with GPA scores of 1.00
      1.74 did not show any gagging or displayed only mild discomfort during the
      procedures. Patients with GPA scores of 1.75-3.24 showed moderate gagging, which
      was managed with prophylactic and suppressive precautions. Patients with GPA
      scores of 3.25-4.00 were unable to complete the procedures because of gagging.
      Differences (all P < 0.001) were found between the three groups for the observed
      responses of patients during radiography (F, 203.343), impression (F, 175.035)
      and radiography + impression procedures (F, 228.319), with no significant
      difference between women and men. In conclusion, GPA may be helpful for the
      prediction of patient sensitivity to dental treatments.

PMID- 22642625
TI  - Descriptive anatomic study of the great vessels of the heart in the capuchin
      monkey Cebus apella (Linnaeus, 1758).
AB  - The aim of this study was to describe the anatomy of the great vessels of the
      heart in capuchin monkey (Cebus apella) and to compare with those of other
      primates, including humans. The hearts were prepared through fixation in 10%
      formalin and subsequently dissected using standard techniques and instruments.
      The arterial and venous systems were perfused with colored latex solution via the
      femoral vessels. An ascending cylindrical branch with relatively great caliber
      was identified in the aorta artery, in addition to an aortic arch, from which
      three great arteries were originated, the brachiocephalic trunk, the left common
      carotid artery and the left subclavian artery. After a course of variable
      extension, the pulmonary trunk divided into right and left pulmonary arteries.
      The caudal vena cava was morphologically similar to that of humans, except for
      its association with the cardiac lobe of the right lung, whereas the cranial vena
      cava was formed by the two braquiocephalic veins and received the azygos vein
      close to right atrium. The pulmonary veins, in number of six, ended at the
      posterior face of the left atrium, differently from both humans and other
      primates. In conclusion, the morphology of the great vessels of the heart in
      Cebus apella was similar to that of humans and other primates, although some
      differences are evidenced with regards to topography and number of anatomic
      structures, particularly the relationship of the caudal vena cava with the
      cardiac lobe of the right lung and the presence of six pulmonary veins in Cebus
      apella.

PMID- 22642627
TI  - Examining the potential of the influenza vaccine for secondary prevention: a
      myocardial infarction vaccine?

PMID- 22642628
TI  - Macrophages, atherosclerosis and the potential of netrin-1 as a novel target for
      future therapeutic intervention.

PMID- 22642626
TI  - Epi4K: gene discovery in 4,000 genomes.
AB  - A major challenge in epilepsy research is to unravel the complex genetic
      mechanisms underlying both common and rare forms of epilepsy, as well as the
      genetic determinants of response to treatment. To accelerate progress in this
      area, the National Institute of Neurological Disorders and Stroke (NINDS)
      recently offered funding for the creation of a "Center without Walls" to focus on
      the genetics of human epilepsy. This article describes Epi4K, the collaborative
      study supported through this grant mechanism and having the aim of analyzing the
      genomes of a minimum 4,000 subjects with highly selected and well-characterized
      epilepsy.

PMID- 22642630
TI  - Heart failure with normal ejection fraction: a growing pandemic.
AB  - Heart failure is a heterogeneous syndrome. Approximately 30-50% of patients with
      heart failure have normal or near normal left ventricle function. Several
      epidemiological studies confirm that the prevalence of heart failure with normal
      ejection fraction is increasing. Given the current trends, heart failure with
      normal ejection fraction will become the most common form of heart failure, for
      which we do not currently have an evidence-based successful treatment. This
      article summarizes the etiology, current recommended guidelines and management
      options for this clinical manifestation.

PMID- 22642631
TI  - Multimodality imaging throughout transcatheter aortic valve implantation.
AB  - Transcatheter aortic valve implantation (TAVI) is a novel, less-invasive
      technique used to treat selected patients with severe aortic valve stenosis with
      a high surgical risk. Noninvasive imaging before, during and after the procedure
      is of the utmost importance in this minimally invasive procedure. Screening of
      the patient and sizing of the aortic root by echocardiography and multislice
      computed tomography is of great importance to ensure success of the TAVI
      procedure. Echocardiography and fluoroscopy are essential during the procedure.
      During follow-up of the patients, echocardiography is important to evaluate the
      prosthesis function, durability and integrity. Additionally, multislice computed
      tomography and MRI might be helpful in the follow-up of selected cases. This
      article outlines the evolving role of multimodality imaging throughout TAVI in
      patients with severe aortic valve stenosis. It describes, in a stepwise approach,
      how multimodality imaging by echocardiography, angiography, multislice computed
      tomography and MRI enhances the TAVI procedure.

PMID- 22642632
TI  - Current and future technologies for remote monitoring in cardiology and evidence
      from trial data.
AB  - All major manufacturers of implantable pacing or defibrillator technologies
      support remote monitoring of their devices. Integration of signals from several
      monitored variables can facilitate earlier detection of arrhythmia or technical
      problems, and can also identify patients at risk of deterioration. Meta-analyses
      of randomized studies of remote monitoring of heart failure using standalone
      systems suggest considerable clinical benefit when compared with usual care.
      However, there may be little to be gained by frequently monitoring patients with
      well-treated stable disease. Trials of implantable monitoring-only devices
      suggest that there is a subgroup of patients that may benefit from such remote
      monitoring. Remote monitoring is still not widely adopted due to a number of
      social, technological and reimbursement issues, but this is likely to change
      rapidly. Remote monitoring will not replace face-to-face clinical review, but it
      will be part of the solution to ever increasing numbers of patients with heart
      failure and/or an implantable device requiring expert input to their care.

PMID- 22642633
TI  - Treatment of asymptomatic catecholaminergic polymorphic ventricular tachycardia.
AB  - Catecholaminergic polymorphic ventricular tachycardia is a rare genetic disorder
      caused by mutations in genes involved in the intracellular calcium homeostasis of
      cardiac cells. Affected patients typically present with life-threatening
      ventricular arrhythmias precipitated by emotional/physical stress. The diagnosis
      is based on the demonstration of polymorphic or bidirectional ventricular
      tachycardia associated with adrenergic stress. Genetic testing can be
      confirmatory in some patients. Treatment for catecholaminergic polymorphic
      ventricular tachycardia includes medical and surgical efforts to suppress the
      effects of epinephrine at the myocardial level and/or modulation of calcium
      homeostasis. Mortality is high when untreated and sudden cardiac death may be the
      first manifestation of the disease. First-degree relatives of a proband should be
      offered genetic testing if the causal mutation is known. If the family mutation
      is not known, relatives should be clinically evaluated with provocative testing.
      In the absence of rigorous trials, prophylactic treatment of the asymptomatic
      catecholaminergic polymorphic ventricular tachycardia patient appears to reduce
      morbidity and mortality.

PMID- 22642635
TI  - Epidemiology and economic impact of cardiac syncope in western countries.
AB  - This article updates our current understanding of the epidemiology and economic
      impact of syncope in western countries. Unfortunately, both of these aspects of
      syncope are inadequately understood; in part the problem is due to the difficulty
      in public health data separating 'true syncope' from conditions that cause other
      forms of transient loss of consciousness. However, in certain respects, the
      epidemiology of syncope is becoming clearer. Similarly, we have come to
      understand that the economic impact of syncope is substantial and is much larger
      than is necessary, primarily because management, especially excessive
      hospitalization, often remains suboptimal.

PMID- 22642634
TI  - Ethical issues in cardiac surgery.
AB  - While ethical behavior has always been part of cardiac surgical practice, ethical
      deliberation has only recently become an important component of cardiac surgical
      practice. Issues such as informed consent, conflict of interest and professional
      self-regulation, among many others, have increasingly attracted the attention of
      cardiac surgeons. This article covers several broad topics of interest to cardiac
      surgeons and cardiologists and discusses several other topics more briefly. There
      is much uncertainty regarding what the future holds for cardiac surgical
      practice, research and culture and we also discuss the background of ethical
      issues to serve as a platform for envisioning what is to come.

PMID- 22642636
TI  - Heart rate variability in patients hospitalized for decompensated diastolic heart
      failure at admission and after clinical stabilization.
AB  - AIMS: We investigated heart rate variability (HRV) in patients hospitalized for
      decompensated diastolic heart failure and the effect of compensation course on
      HRV parameters. We also examined the association between the degree of diastolic
      dysfunction and HRV indices. PATIENTS & METHODS: A total of 42 patients
      hospitalized for decompensated heart failure, who had a measured ejection
      fraction >= 50%, and ten age- and sex-matched healthy volunteers were enrolled.
      RESULTS: All HRV indices were lower compared with the control group both at
      admission (p < 0.001) and after compensation, although a significant increase was
      observed in each index measured after clinical stabilization (p < 0.001).
      Improvement in HRV indices was lowest in patients with a restrictive pattern
      among groups of different degrees of diastolic dysfunction. CONCLUSION:
      Impairment in HRV in decompensated diastolic heart failure is more pronounced
      with increasing grade of diastolic dysfunction. It remains to be investigated
      whether decompensation may be predicted by marked depression in these indexes or
      if severely impaired HRV is a consequence of decompensation.

PMID- 22642638
TI  - Postprandial hypotension among older residents of a nursing home in Korea.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to identify changes in blood
      pressure and pulse rate after a meal for elders living in a nursing home.
      BACKGROUND: Postprandial hypotension is a major health issue for older persons,
      because it has been shown to cause increased incidence of falls, syncope,
      coronary disease, strokes and deterioration in the quality of life. However,
      there has been little systematic investigation into blood pressure changes after
      meals in older people. DESIGN: A descriptive, cross-sectional design was used to
      identify postprandial blood pressure and pulse rate changes in residents of a
      nursing home. METHOD: Blood pressure and pulse rates of 121 people aged 65 and
      above were measured before and after a meal and at 15-minute intervals for six
      more measurements. Data were analysed with descriptive statistics, repeated
      measures anova and paired t-tests using SPSS (SPSS Inc., Chicago, IL, USA).
      RESULTS: There were significant differences in systolic and diastolic pressure by
      time. The biggest drop in systolic and diastolic blood pressure occurred at 45
      minutes after the meal. There was no significant change in pulse rates except for
      immediately after the meal. CONCLUSIONS: To prevent complications from drops in
      postprandial blood pressure, nurses should carefully monitor blood pressure of
      elders at least from 30-90 minutes after meals. Further study of drops in
      postprandial blood pressure should be conducted for various types and times of
      meals. RELEVANCE TO CLINICAL PRACTICE: Nurses caring for older persons can
      identify drops in the postprandial blood pressure to manage the incidence of
      falls, syncope and stroke more effectively, especially in nursing homes.

PMID- 22642639
TI  - Up-regulation of blood arachidonate (20:4) levels in patients with chronic
      obstructive pulmonary disease.
AB  - CONTEXT AND OBJECTIVE: Plasma arachidonate (20:4) levels in patients with chronic
      obstructive pulmonary disease (COPD) were investigated. METHODS: Plasma was
      extracted and free fatty acids (FFAs) were separated using column chromatography
      and measured by fluorescence. Plasma 20:4 levels and its percentage relative to
      total FFA levels (%20:4) were measured in COPD (n = 18) and control (n = 20)
      subjects. RESULTS AND CONCLUSIONS: FFA levels were lower in COPD compared with
      normals. However, there was a significant increase in %20:4 levels in COPD
      patients (GOLD stage I/II 0.9 +/- 0.4%; GOLD stage III/IV 1.1 +/- 0.1%) compared
      with control subjects (0.6 +/- 0.1, p < 0.05). %20:4 is a potential biomarker for
      COPD.

PMID- 22642640
TI  - Distance coursework and coaching to improve nursing home incontinence care:
      lessons learned.
AB  - OBJECTIVES: To determine whether a distance coaching course on improving nursing
      home incontinence care could be replicated and brought to scale with a larger
      group of nursing homes without sacrificing outcomes. DESIGN: The study collected
      descriptive and comparative data. SETTING: Fourteen nursing homes in the original
      course and 34 in the replication course. PARTICIPANTS: Participants in the study
      were supervisors and staff from enrolled nursing homes who completed the distance
      coaching courses on incontinence management. MEASUREMENTS: Data for both courses
      were collected using a resident assessment form to evaluate implementation of new
      practices, pre- and posttraining quizzes, a course evaluation survey, and a
      supervisor's report. RESULTS: There were few significant differences between the
      course groups with respect to course participation, knowledge transfer, and
      training program preferences. Although Course 1 nursing homes reported assessing
      more residents on average than Course 2 homes (22 vs 12), this difference is
      probably an artifact of differences in the reporting methodologies for the two
      courses. CONCLUSION: This study found qualified support for using a distance
      coaching course to facilitate adoption of evidence-based incontinence care
      practices in nursing homes. The findings also underscore the challenges
      associated with designing dissemination and implementation programs that are
      effective and feasible to implement with nursing homes. Nursing home educators
      should consider this study's findings when designing new training programs.
      Outcomes may improve if some dissemination resources are diverted to distance
      coaching activities that support nursing home improvement efforts over extended
      periods.

PMID- 22642641
TI  - Effects of lithium salts on shear relaxation spectra of pyrrolidinium-based ionic
      liquids.
AB  - The shear relaxation spectra of the solutions of lithium salts in ionic liquids
      composed of N-methyl-N-propylpyrrolidinium cation paired with
      bis(trifluoromethanesulfonyl)amide (TFSA(-)) or bis(fluorosulfonyl)amide (FSA(-))
      anions are determined from 5 to 205 MHz at various concentrations of lithium
      salts. The addition of lithium salt retards the shear relaxation, together with
      the increase in the shear viscosity. The normalized spectra reduce to a single
      curve when plotted against the product of the frequency and zero-frequency shear
      viscosity, which indicates that the increase in the shear viscosity by lithium
      salts is ascribed to the increase in the relaxation time. The difference in the
      shear viscosity of TFSA- and FSA-based ionic liquids is also elucidated in terms
      of the shear relaxation time. The relationship with previous studies on ionic
      mobility and liquid structure is also discussed.

PMID- 22642642
TI  - The stem cell factor antibody enhances the chemotherapeutic effect of adriamycin
      on chemoresistant breast cancer cells.
AB  - BACKGROUND: The outcome of chemotherapy in breast cancer is strongly influenced
      by multidrug resistance (MDR). Several surrogate markers of chemoresistance have
      been identified including - CD24 (cluster differentiation 24) expression, stem
      cell growth factor (SCF), B-cell lymphocyte protein 2 (Bcl-2) and annexin V. The
      present study aimed to examine the expression of CD24 in the sensitive breast
      cancer cell line MCF-7 (Michigan Foudation-7) and MCF-7/adriamycin resistant (MCF
      7/AdrRes) cells, and, if minimal effective doses of the anthracycline drug
      adriamycin (0.579 MUM and 88.2 MUM) would be enhanced by the antibody to SCF
      (anti-SCF). METHODS: CD24 expression was analysed by flow cytometry. Both Bcl-2
      and annexin V protein expression were quantitatively assessed by the enzyme
      linked immunosorbent assay (ELISA). RESULTS: In MCF-7/AdrRes cells the expression
      of CD24 was significantly higher compared to MCF-7 cells, 86.6% and 16.3% (p <
      0.001), respectively. Bcl-2 expression was significantly increased in the
      presence of adriamycin and SCF (p < 0.038) and decreased in the presence of
      adriamycin and anti-SCF. When adriamycin, anti-SCF and SCF were combined or when
      adriamycin was used alone the decrease in Bcl-2 expression was insignificantly
      altered. In the presence of both adriamycin and SCF the expression of annexin V
      was decreased. However, it was significantly increased in the presence of
      adriamycin and anti-SCF (p < 0.042), as well as adriamycin, anti-SCF and SCF
      combined.In MCF-7 cells the effect of adriamycin alone or with either SCF, anti
      SCF or anti-SCF or SCF combined, did not significantly alter the expression of
      Bcl-2. However, in the presence of both adriamycin and SCF the expression of
      annexin V was decreased, but was significantly increased in the presence of
      adriamycin and anti-SCF (p < 0.001), adriamycin, anti-SCF and SCF combined and
      adriamycin alone. Our results demonstrate that anti-SCF with low dose of
      adriamycin reduces Bcl-2 expression in MCF-7/AdrRes cells and increases annexin V
      expression in both MCF7/AdrRes and MCF-7 cells. CONCLUSION: Adding anti-SCF to
      the chemotherapeutic regime of adriamycin may strongly enhance its
      chemotherapeutic effect in the treatment of patients with breast cancer.

PMID- 22642643
TI  - An experimental study of VEGF induced changes in vasoactivity in pig retinal
      arterioles and the influence of an anti-VEGF agent.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in
      ocular physiology. Anti-VEGF agents are now used for treatment of common retinal
      diseases. This study characterises the vasoactive properties of VEGF in isolated
      perfused pig retinal arterioles under normal tone or endothelin-1 (ET-1) pre
      contracted conditions and determines the influence of an anti VEGF agent on VEGF
      induced vasoactivity. METHODS: An isolated perfused retinal arteriole preparation
      was used. The outer diameter of retinal vessels was monitored at 2 second
      intervals in response to VEGF and the anti VEGF agent, bevacizumab. The effect of
      intraluminal delivery of VEGF was determined over a wide concentration range (10(
      16) to 10(-7) M) both with and without pre-contraction with ET-1 (3 x 10(-9) M).
      Bevacizumab (0.35 mg mL(-1)) was applied extraluminally to determine the
      influence of bevacizumab on VEGF induced vasoactive changes on ET-1 pre
      contracted vessels. RESULTS: In retinal arterioles with normal tone, VEGF induced
      a concentration dependent contraction at low concentrations, reaching 93.5% at
      10(-11) M and then contraction was reduced at higher concentrations, recovering
      to 98.1% at 10-7 M. VEGF produced a potent concentration dependent vasodilatation
      in arterioles pre-contracted with ET-1. VEGF induced vasodilatation in arterioles
      pre-contracted with ET-1 was significantly inhibited by bevacizumab. CONCLUSIONS:
      VEGF induced vasoactive changes in pig retinal arterioles are dependent on
      concentration and vascular tone. Bevacizumab inhibits VEGF-induced vasodilatation
      in pre-contracted arterioles.

PMID- 22642644
TI  - The impact of copper, nitrate and carbon status on the emission of nitrous oxide
      by two species of bacteria with biochemically distinct denitrification pathways.
AB  - Denitrifying bacteria convert nitrate (NO(3) (-) ) to dinitrogen (N(2) ) gas
      through an anaerobic respiratory process in which the potent greenhouse gas
      nitrous oxide (N(2) O) is a free intermediate. These bacteria can be grouped into
      classes that synthesize a nitrite (NO(2) (-) ) reductase (Nir) that is solely
      dependent on haem-iron as a cofactor (e.g. Paracoccus denitrificans) or a Nir
      that is solely dependent on copper (Cu) as a cofactor (e.g. Achromobacter
      xylosoxidans). Regardless of which form of Nir these groups synthesize, they are
      both dependent on a Cu-containing nitrous oxide reductase (NosZ) for the
      conversion of N(2) O to N(2) . Agriculture makes a major contribution to N(2) O
      release and it is recognized that a number of agricultural lands are becoming Cu
      limited but are N-rich because of fertilizer addition. Here we utilize continuous
      cultures to explore the denitrification phenotypes of P. denitrificans and A.
      xylosoxidans at a range of extracellular NO(3) (-) , organic carbon and Cu
      concentrations. Quite distinct phenotypes are observed between the two species.
      Notably, P. denitrificans emits approximately 40% of NO(3) (-)  consumed as N(2)
      O under NO(3) (-) -rich Cu-deficient conditions, while under the same conditions
      A. xylosoxidans releases approximately 40% of the NO(3) (-)  consumed as NO(2) (
      ) . However, the denitrification phenotypes are very similar under NO(3) (-) 
      limited conditions where denitrification intermediates do not accumulate
      significantly. The results have potential implications for understanding
      denitrification flux in a range of agricultural environments.

PMID- 22642645
TI  - Toward a visible light mediated photocyclization: Cu-based sensitizers for the
      synthesis of [5]helicene.
AB  - A photochemical synthesis of [5]helicene employing a copper-based sensitizer 7
      has been developed that avoids the disadvantages associated with the traditional
      UV light mediated method. The visible light mediated synthesis uses common
      glassware and a simple household light bulb without the competing formation of [2
      + 2] cycloadducts, regioisomers, or the overoxidation product benzo[ghi]perylene
      3. Preliminary results show that the reaction time can be significantly reduced
      through the use of a continuous flow strategy.

PMID- 22642646
TI  - Comparison of heart rate variability parameters during complex partial seizures
      and psychogenic nonepileptic seizures.
AB  - PURPOSE: Psychogenic nonepileptic seizures (PNES) superficially resemble
      epileptic seizures. Little is known about ictal autonomic nervous system (ANS)
      activity changes in epilepsy and PNES. This study compares ictal heart rate
      variability (HRV) parameters as a reflection of ANS tone in epileptic seizures
      and PNES, and explores differences between interictal and ictal ANS tone in both
      patient groups. METHODS: Ictal HRV parameters were extracted from single-lead
      electrocardiography (ECG) data collected during video-electroencephalography
      (EEG) recordings of 26 patients with medically refractory temporal lobe epilepsy
      and 24 age- and sex-matched patients with PNES. One seizure per patient in a
      resting, wake, supine state was analyzed. Interictal ECG data were available for
      comparison from 14 patients in both groups. HRV parameters in time and frequency
      domains were analyzed (low frequency [LF], high frequency [HF], standard
      deviation of all consecutive normal R wave intervals [SDNN], square root of the
      mean of the sum of the squares of differences between adjacent normal R wave
      intervals [RMSSD]). CVI (cardiovagal index), CSI (cardiosympathetic index), and
      ApEn (approximate entropy) were calculated from Lorenz plots. KEY FINDINGS: There
      were significant differences between ictal HRV measures during epileptic and
      nonepileptic seizures in the time and frequency domains. CSI (p < 0.001) was
      higher in epileptic seizures. Time interval between two consecutive R waves in
      the ECG (RR interval) (p = 0.002), LF (p = 0.02), HF (p = 0.003), and RMSSD (p =
      0.003) were significantly lower during epileptic seizures. Binary logistic
      regression yielded a significant model based on the differences in CSI
      classifying 88% of patients with epilepsy and 73% of patients with PNES
      correctly. The comparison between resting and ictal states in both seizure
      disorders revealed significant differences in RR interval (epilepsy p < 0.001,
      PNES p = 0.01), CSI (epilepsy p < 0.001, PNES p = 0.02), HF (epilepsy p = 0.002,
      PNES p = 0.03), and RMSSD (epilepsy p = 0.004, PNES p = 0.04). In patients with
      epilepsy there were also significant differences in ictal versus interictal mean
      values of ApEn (p = 0.03) and LF (p = 0.04). Although CSI was significantly
      higher, the other parameters were lower during the seizures. Stepwise binary
      regression in the 14 patients with epilepsy produced a significant model
      differentiating resting state from seizures in 100% of cases. The same
      statistical approach did not yield a significant model in the PNES group.
      SIGNIFICANCE: Our results show greater ANS activation in epileptic seizures than
      in PNES. The biggest ictal HRV changes associated with epileptic seizures (CSI,
      HF, and RMSSD) reflect high sympathetic system activation and reduced vagal tone.
      The reduced ApEn also reflects a high sympathetic tone. The observed ictal
      alterations of HRV patterns may be a more specific marker of epileptic seizures
      than heart rate changes alone. These altered HRV patterns could be used to detect
      seizures and also to differentiate epileptic seizures from PNES. Larger studies
      are justified with intergroup and intragroup comparisons between ictal and
      resting states.

PMID- 22642647
TI  - Oral administration of milk fermented with Lactococcus lactis subsp. cremoris FC
      protects mice against influenza virus infection.
AB  - AIMS: To evaluate the protective effects of oral administration of milk fermented
      with a Lactococcus strain against influenza virus (IFV) infection in a mouse
      model. METHODS AND RESULTS: Milk fermented with exopolysaccharide-producing
      Lactococcus lactis subsp. cremoris (L. cremoris) FC was orally administered to
      BALB/c mice for 12 days. Mice were intranasally infected with IFV A/New
      Caledonia/20/99 (H1N1) on day 8, and survival was determined for 14 days after
      IFV infection. Survival rate and body weight loss after IFV infection in the L.
      cremoris FC fermented milk-administered group were significantly improved
      compared with those in the control group. In the unfermented milk-administered
      group, survival rate was not improved, whereas body weight loss was slightly
      improved compared with that in the control group. The mean virus titre in the
      lung of the L. cremoris FC fermented milk-administered group 3 days after
      infection was significantly decreased compared with that in the control group.
      CONCLUSIONS: These results suggest that oral administration of milk fermented
      with L. cremoris FC protects mice against IFV infection. SIGNIFICANCE AND IMPACT
      OF THE STUDY: These results demonstrate that oral administration of milk
      fermented with exopolysaccharide-producing Lactococcus strains might protect host
      animals against IFV infection.

PMID- 22642648
TI  - Haplotype combination of the bovine INSIG1 gene sequence variants and association
      with growth traits in Nanyang cattle.
AB  - The insulin-induced gene 1 (INSIG1) gene encodes a protein that blocks
      proteolytic activation of sterol regulatory element binding proteins, which are
      transcription factors that activate genes that regulate cholesterol, fatty acid,
      and glucose metabolism. However, similar research for the bovine INSIG1 gene is
      lacking. Therefore, in this study, polymorphisms of the bovine INSIG1 gene were
      detected in 643 individuals from four cattle breeds by DNA pooling, forced PCR
      RFLP, PCR-SSCP, and DNA sequencing methods. Only 10 novel SNPs were identified,
      which included four mutations in the coding region and the others in the introns.
      In Nanyang individuals, seven common haplotypes were identified based on four
      coding region SNPs. The haplotype GACT, with a frequency of 75.4%, was the most
      prevalent haplotypes and SNPs formed two linkage disequilibrium blocks with
      strong multi-allelic D' (D' = 1). Additionally, association analysis between
      mutations of the bovine INSIG1 gene and growth traits in Nanyang cattle at 6, 12,
      18, and 24 months old was performed, and the results indicated that the
      polymorphisms were not significantly associated with body mass.

PMID- 22642649
TI  - Neuroprotective effect of small interfering RNA targeted to caspase-3 on rat
      retinal ganglion cell loss induced by ischemia and reperfusion injury.
AB  - PURPOSE: To investigate neuroprotective effects of siRNA targeted to caspase-3
      against ischemia and reperfusion (I/R) injury in rat eyes. METHODS: Retinal
      ischemia was induced in Wistar rats by increasing the intraocular pressure (IOP)
      to 110 mmHg for 120 min. To examine the effect of siRNA on rat caspase-3, siRNA
      was injected into the vitreous cavity 24 h prior to induction of retinal
      ischemia. Eyes were removed at 2, 7 or 14 days later, and then analyzed for the
      number of retinal ganglion cells (RGCs), the retinal thickness and the amount of
      apoptosis of the retinal neural cells (as demonstrated by the TUNEL assay). The
      amount of caspase-3 mRNA was analyzed by rt-PCR. Differences between groups were
      evaluated by an unpaired t test. RESULTS: The numbers of RGCs in the saline and
      non-silencing siRNA controls were reduced significantly at 2 and 7 days after the
      I/R injury. RGCs were significantly retained in eyes pretreated with siRNA
      targeted to caspase-3 as compared to the control eyes at 2 days after the I/R
      injury. Inner retinal thickness in the control eyes was significantly thinner as
      compared to the treated eyes at 2 and 7 days after the I/R injury. After siRNA
      treatment, the amount of caspase-3 mRNA was significantly lower when compared to
      the saline control group. CONCLUSIONS: The injection of siRNA targeted to caspase
      3 into the vitreous cavity of rat eyes may block caspase-3, and may thus be able
      to prevent retinal cell death associated with ischemic injury. As inhibition of
      the apoptosis pathway may provide a neuroprotective effect, examination of new
      strategies for treating these disorders needs to be undertaken.

PMID- 22642650
TI  - Dissecting intramural hematoma of the esophagus.

PMID- 22642651
TI  - Conn: a functional connectivity toolbox for correlated and anticorrelated brain
      networks.
AB  - Resting state functional connectivity reveals intrinsic, spontaneous networks
      that elucidate the functional architecture of the human brain. However, valid
      statistical analysis used to identify such networks must address sources of noise
      in order to avoid possible confounds such as spurious correlations based on non
      neuronal sources. We have developed a functional connectivity toolbox Conn (
      www.nitrc.org/projects/conn ) that implements the component-based noise
      correction method (CompCor) strategy for physiological and other noise source
      reduction, additional removal of movement, and temporal covariates, temporal
      filtering and windowing of the residual blood oxygen level-dependent (BOLD)
      contrast signal, first-level estimation of multiple standard functional
      connectivity magnetic resonance imaging (fcMRI) measures, and second-level random
      effect analysis for resting state as well as task-related data. Compared to
      methods that rely on global signal regression, the CompCor noise reduction method
      allows for interpretation of anticorrelations as there is no regression of the
      global signal. The toolbox implements fcMRI measures, such as estimation of seed
      to-voxel and region of interest (ROI)-to-ROI functional correlations, as well as
      semipartial correlation and bivariate/multivariate regression analysis for
      multiple ROI sources, graph theoretical analysis, and novel voxel-to-voxel
      analysis of functional connectivity. We describe the methods implemented in the
      Conn toolbox for the analysis of fcMRI data, together with examples of use and
      interscan reliability estimates of all the implemented fcMRI measures. The
      results indicate that the CompCor method increases the sensitivity and
      selectivity of fcMRI analysis, and show a high degree of interscan reliability
      for many fcMRI measures.

PMID- 22642652
TI  - Synthesis of oxidation-resistant cupronickel nanowires for transparent conducting
      nanowire networks.
AB  - Nanowires of copper can be coated from liquids to create flexible, transparent
      conducting films that can potentially replace the dominant transparent conductor,
      indium tin oxide, in displays, solar cells, organic light-emitting diodes, and
      electrochromic windows. One issue with these nanowire films is that copper is
      prone to oxidation. It was hypothesized that the resistance to oxidation could be
      improved by coating copper nanowires with nickel. This work demonstrates a method
      for synthesizing copper nanowires with nickel shells as well as the properties of
      cupronickel nanowires in transparent conducting films. Time- and temperature
      dependent sheet resistance measurements indicate that the sheet resistance of
      copper and silver nanowire films will double after 3 and 36 months at room
      temperature, respectively. In contrast, the sheet resistance of cupronickel
      nanowires containing 20 mol % nickel will double in about 400 years. Coating
      copper nanowires to a ratio of 2:1 Cu:Ni gave them a neutral gray color, making
      them more suitable for use in displays and electrochromic windows. These
      properties, and the fact that copper and nickel are 1000 times more abundant than
      indium or silver, make cupronickel nanowires a promising alternative for the
      sustainable, efficient production of transparent conductors.

PMID- 22642653
TI  - Enucleation and evisceration: 20 years of experience.
AB  - OBJECTIVE: To determine the indications, relative frequencies, surgical times,
      and complications for enucleation and evisceration performed at a single academic
      center. METHODS: Medical records of all patients who underwent an enucleation or
      evisceration between January 1st, 1990 and December 31st, 2009 at a single
      academic center were reviewed. Patient demographics and surgical indications,
      times, and complications were recorded. RESULTS: A total of 85 eyes in 85
      patients underwent enucleation (n = 31; 36%) or evisceration (n = 54; 64%) during
      the study period. Almost all patients were of African descent (96%). The most
      common underlying cause leading to eye removal was trauma. On average,
      eviscerations (47.3 +/- 10.3 minutes) took significantly less time to perform
      than enucleations (89.6 +/- 10.1 minutes; p < 0.01). Complications included
      implant exposure, infection, lower lid laxity, fornix insufficiency, and need for
      subsequent surgery; the occurrence of these complications was found to be similar
      between the two groups (p = 0.77). No case of sympathetic ophthalmia or
      inadvertent evisceration of an eye with an occult intraocular malignancy was
      noted. From the first decade for which data were available (1990- 1999) to the
      second decade (2000- 2009), the average number of enucleations decreased (p =
      0.02) and the average number of eviscerations (p = 0.04) increased. CONCLUSION:
      Evisceration was found to be a safe and quicker alternative to enucleation in our
      study. A change in surgical preference from enucleation to evisceration was seen
      during the 20-year study period.

PMID- 22642655
TI  - Categorized or continuous? Strength of an association--and linear regression.

PMID- 22642656
TI  - Contrast-induced nephropathy: protective role of fenoldopam.
AB  - 1. Contrast-induced nephropathy (CIN) often occurs after contrast media-related
      procedures and is associated with increased morbidity and mortality. The acute
      renal failure observed after administration of contrast media is usually
      transient but, in some cases, it can be severe enough to lead to permanent renal
      damage with life-long dialysis. 2. Except for saline hydration, no other
      treatment has been shown to have a consistent benefit in protecting against CIN.
      Despite sound physiological and pharmacological bases, intravenous infusion of
      fenoldopam does not prevent CIN. 3. Initial studies have shown the safety of and
      favourable results with direct infusion of fenoldopam into the renal arteries
      using the Benephit renal infusion system (FlowMedica-AngioDynamics, Latham, NY,
      USA). These results are encouraging and suggest that intrarenal delivery of
      fenoldopam has an advantage in patients with a high risk of developing CIN. 4. A
      randomized controlled study comparing intrarenal fenoldopam with placebo is
      warranted.

PMID- 22642657
TI  - Pharmacokinetics and pharmacodynamics of insulin aspart in patients with type 2
      diabetes: assessment using a meal tolerance test under clinical conditions.
AB  - 1. Few studies have evaluated the pharmacokinetics of rapid-acting insulin
      analogues in patients with Type 2 diabetes, especially under clinical conditions.
      The aim of the present study was to assess both the pharmacokinetics and
      pharmacodynamics of insulin aspart in Type 2 diabetic patients who were being
      treated with the analogue alone. 2. Meal tolerance tests with and without self
      injection of a customary dose of insulin aspart (0.05-0.22 U/kg) were conducted
      in 20 patients in a randomized cross-over study. 3. The dose of insulin aspart
      (per bodyweight) was significantly correlated with both the maximum concentration
      (r(2) = 0.59; P < 0.01) and area under the concentration-time curve for insulin
      aspart (r(2) = 0.53; P < 0.01). However, the time to maximum concentration
      (T(max)), which varied widely from < 60 to >= 120 min, was not associated with
      either dosage (r(2) = 0.02; P = 0.51) or body mass index (r(2) = 0.02; P = 0.57).
      Injection of insulin aspart exacerbated delayed hyperinsulinaemia after meal
      loading, mainly in patients with T(max) >= 120 min. With regard to
      pharmacodynamics, insulin aspart had favourable effects on postprandial
      hyperglycaemia, hyperglucagonaemia and hyperlipidaemia. 4. The T(max) for this
      insulin analogue differed greatly between individuals and delayed
      hyperinsulinaemia was particularly exacerbated in patients with higher T(max)
      values. Identification of the factors contributing to interindividual variation
      in the absorption lag time is essential for improving the efficacy and safety of
      insulin aspart.

PMID- 22642658
TI  - Fall prediction according to nurses' clinical judgment: differences between
      medical, surgical, and geriatric wards.
AB  - OBJECTIVES: To assess the value of nurses' clinical judgment (NCJ) in predicting
      hospital inpatient falls. DESIGN: Prospective multicenter study. SETTING: Six
      Belgian hospitals. PARTICIPANTS: Two thousand four hundred seventy participants
      (mean age 67.6 +/- 18.3; female, 55.7%) on four surgical (n = 812, 32.9%), eight
      geriatric (n = 666, 27.0%), and four general medical wards (n = 992, 40.1%) were
      included upon admission. All participants were hospitalized for at least 48
      hours. MEASUREMENTS: Within 24 hours after admission, nurses gave their judgment
      on the question "Do you think your patient is at high risk for falling?" Nurses
      were not trained in assessing fall risk. Falls were documented on a standardized
      incident report form. RESULTS: During hospitalization, 143 (5.8%) participants
      experienced one or more falls, accounting for 202 falls and corresponding to an
      overall rate of 7.9 falls per 1,000 patient days. NCJ of participant's risk of
      falling had high sensitivity (78-92%) with high negative predictive value (94
      100%) but low positive predictive value (4-17%). Although false-negative rates
      were low (8-22%) for all departments and age groups, false-positive rates were
      high (55-74%), except on surgical and general medical wards and in participants
      younger than 75. CONCLUSION: This analysis, based on multicenter data and a large
      sample size, suggests that NCJ can be recommended on surgical and general medical
      wards and in individuals younger than 75, but on geriatric wards and in
      participants aged 75 and older, NCJ overestimates risk of falling and is thus not
      recommended because expensive comprehensive fall-prevention measures would be
      implemented in a large number of individuals who do not need it.

PMID- 22642659
TI  - Characteristics of hypertension-related factors in female home caregivers in
      Japan-comparison with general community non-caregivers.
AB  - AIMS AND OBJECTIVES: To examine the characteristics of hypertension-related
      factors in female family caregivers in Japan who provide care in the home, in
      comparison with general community non-caregivers. BACKGROUND: Hypertension is
      more frequently encountered in female caregivers than in non-caregivers.
      Lifestyle factors including sleep and eating habits differ in Japanese female
      caregivers and the general population. Therefore, hypertension-related factors in
      caregivers may also differ from those in the general population. DESIGN: A cross
      sectional study. METHODS: The subjects were 150 female caregivers (aged 62.4, SD
      12.2 years) who provided home care for persons with physical impairments and/or
      dementia and 154 female controls (aged 62.7, SD 2.2 years) who did not provide
      home care. Persons with a history of ischaemic heart disease or cerebral stroke
      were excluded. Subjects were examined using a self-reporting questionnaire that
      included a food frequency questionnaire and the tri-axial coping scale. Urine
      examinations and blood pressure measurements were also done. Logistic regression
      analysis was conducted for each group with the same variables as explanatory
      variables. RESULTS: Hypertension was present in 46.7% of caregivers and 34.4% of
      controls (p<0.05). Menopause was a factor related to hypertension in both the
      caregivers and controls. In the caregiver group, hypertension was associated with
      the estimated 24-h Na excretion in urine and the carbohydrate-energy ratio for
      nutriti. BMI was associated with hypertension in the control group, but not in
      the caregiver group. CONCLUSIONS: Hypertension was associated with nutritional
      factors, such as greater Na excretion in urine and higher carbohydrate energy
      ratio, in Japanese female caregivers and with obesity in non-caregivers.
      RELEVANCE TO CLINICAL PRACTICE: To prevent hypertension, it is necessary to
      carefully monitor salt intake and nutritional balance in female caregivers in
      Japan.

PMID- 22642661
TI  - Trends in the knowledge, attitudes and practices of travel risk groups towards
      prevention of malaria: results from the Dutch Schiphol Airport Survey 2002 to
      2009.
AB  - BACKGROUND: Previous studies investigating the travellers' knowledge, attitudes
      and practices (KAP) profile indicated an important educational need among those
      travelling to risk destinations. Initiatives to improve such education should
      target all groups of travellers, including business travellers, those visiting
      friends and relatives (VFRs), and elderly travellers. METHODS: In the years 2002
      to 2009, a questionnaire-based survey was conducted at the Dutch Schiphol Airport
      with the aim to study trends in KAP of travel risk groups towards prevention of
      malaria. The risk groups last-minute travellers, solo-travellers, business
      travellers, VFRs and elderly travellers were specifically studied. RESULTS: A
      total of 3,045 respondents were included in the survey. Travellers to
      destinations with a high risk for malaria had significantly more accurate risk
      perceptions (knowledge) than travellers to low-risk destinations. The relative
      risk for malaria in travellers to high-risk destinations was probably mitigated
      by higher protection rates against malaria as compared with travellers to low
      risk destinations. There were no significant differences in intended risk-taking
      behaviour. Trend analyses showed a significant change over time in attitude
      towards more risk-avoiding behaviour and towards higher protection rates against
      malaria in travellers to high-risk destinations. The KAP profile of last-minute
      travellers substantially increased their relative risk for malaria, which
      contrasts to the slight increase in relative risk of solo travellers, business
      travellers and VFRs for malaria. CONCLUSIONS: The results of this sequential
      cohort survey in Dutch travellers suggest an annual 1.8% increase in protection
      rates against malaria coinciding with an annual 2.5% decrease in intended risk
      seeking behaviour. This improvement may reflect the continuous efforts of travel
      health advice providers to create awareness and to propagate safe and healthy
      travel. The KAP profile of last-minute travellers, in particular, substantially
      increased their relative risk for malaria, underlining the continuous need for
      personal protective measures and malaria chemoprophylaxis for this risk group.

PMID- 22642662
TI  - Partial solvation parameters and mixture thermodynamics.
AB  - The recently introduced partial solvation parameters (PSPs) are molecular
      descriptors that combine elements from quantum mechanics with the
      QSPR/LSER/solvatochromic and solubility parameter approaches. Basic regularities
      and universalities exhibited by PSPs are examined in this work and the concepts
      of homosolvation, heterosolvation and solvation energy density are quantified. A
      simple consistent thermodynamic framework is developed, through which the
      validity of the PSP approach is tested. The predictions are compared with
      experimental phase equilibrium data that span the full composition range from the
      pure fluid state to infinite dilution. They include vapor-liquid equilibria of
      fluids interacting with strong specific forces, dissolution of solids/liquids in
      various solvents and probe/oligomer or probe/polymer interactions as typically
      determined by inverse gas-chromatography. These applications show the potential
      of the PSP approach not only to reasonably predict a variety of properties of
      classes of complex systems but, also, to shed light to challenging aspects of
      intermolecular interactions. The perspectives of this unified approach to
      solution thermodynamics are discussed.

PMID- 22642663
TI  - Abernethy malformation: a case report.
AB  - BACKGROUND: Abernethy malformation is a very rare congenital vascular
      malformation defined by diversion of portal blood away from liver. It is commonly
      associated with multiple congenital anomalies. We present a case of Abernethy
      malformation, without associated congenital anomalies from India. CASE
      PRESENTATION: A 5-year-old female child presented with short history of jaundice.
      A provisional diagnosis of acute viral hepatitis was made in view of clinical
      presentation and local endemicity of viral hepatitis A. Persistence of jaundice
      on follow up after 4 weeks led to detailed investigations. Ultrasound and doppler
      study of abdomen revealed drainage of portal vein into inferior vena cava. CT
      angiography was performed which confirmed the diagnosis of Type 1 b Abernethy
      malformation without associated major anomalies. We discuss the common clinical
      presentations, associated anomalies, diagnostic workup and treatment options of
      this disorder. CONCLUSION: The treatment of the patients with congenital porto
      systemic shunts depends on the site of the shunt, associated congenital anomalies
      and the extent of liver damage but the prognosis depends on the complications
      irrespective of anatomical type. However, the extent of associated abnormalities
      should not deter paediatricians to refer patients for treatment. Whenever
      possible closure of the shunt should be advised for cure or to prevent
      complications. Only symptomatic type I patients with absence of possibility to
      close the shunt may require liver transplant. Long-term follow-up is indicated
      for all patients.

PMID- 22642665
TI  - Production of the antimicrobial peptides Caseicin A and B by Bacillus isolates
      growing on sodium caseinate.
AB  - AIMS: The aim of this study was to identify Bacillus isolates capable of
      degrading sodium caseinate and subsequently to generate bioactive peptides with
      antimicrobial activity. METHODS AND RESULTS: Sodium caseinate (2.5% w/v) was
      inoculated separately with 16 Bacillus isolates and allowed to ferment overnight.
      Protein breakdown in the fermentates was analysed using gel permeation-HPLC (GP
      HPLC) and screened for peptides (<3-kDa) with MALDI-TOF mass spectrometry.
      Caseicin A (IKHQGLPQE) and caseicin B (VLNENLLR), two previously characterized
      antimicrobial peptides, were identified in the fermentates of both Bacillus
      cereus and Bacillus thuringiensis isolates. The caseicin peptides were
      subsequently purified by RP-HPLC and antimicrobial assays indicated that the
      peptides maintained the previously identified inhibitory activity against the
      infant formula pathogen Cronobacter sakazakii. CONCLUSIONS: We report a new
      method using Bacillus sp. to generate two previously characterized antimicrobial
      peptides from casein. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights
      the potential to exploit Bacillus sp. or the enzymes they produce for the
      generation of bioactive antimicrobial peptides from bovine casein.

PMID- 22642664
TI  - Manganese-enhanced magnetic resonance imaging detects mossy fiber sprouting in
      the pilocarpine model of epilepsy.
AB  - PURPOSE: Mossy fiber sprouting (MFS) is a frequent finding following status
      epilepticus (SE). The present study aimed to test the feasibility of using
      manganese-enhanced magnetic resonance imaging (MEMRI) to detect MFS in the
      chronic phase of the well-established pilocarpine (Pilo) rat model of temporal
      lobe epilepsy (TLE). METHODS: To modulate MFS, cycloheximide (CHX), a protein
      synthesis inhibitor, was coadministered with Pilo in a subgroup of animals. In
      vivo MEMRI was performed 3 months after induction of SE and compared to the neo
      Timm histologic labeling of zinc mossy fiber terminals in the dentate gyrus (DG).
      KEY FINDINGS: Chronically epileptic rats displaying MFS as detected by neo-Timm
      histology had a hyperintense MEMRI signal in the DG, whereas chronically
      epileptic animals that did not display MFS had minimal MEMRI signal enhancement
      compared to nonepileptic control animals. A strong correlation (r = 0.81, p <
      0.001) was found between MEMRI signal enhancement and MFS. SIGNIFICANCE: This
      study shows that MEMRI is an attractive noninvasive method for detection of mossy
      fiber sprouting in vivo and can be used as an evaluation tool in testing
      therapeutic approaches to manage chronic epilepsy.

PMID- 22642666
TI  - Synthesis and biological evaluation of oral prodrugs based on the structure of
      gemcitabine.
AB  - A series of oral prodrugs based on the structure of gemcitabine (2',2'
      difluorodeoxycytidine) were synthesised by introducing an amide group at the N4
      position of the cytidine ring. A total of 16 compounds were obtained, and their
      chemical and biological characteristics were evaluated. The half-maximal
      inhibitory concentrations (IC(50)s) for most of these compounds were higher than
      that of gemcitabine in vitro. Compounds 5d and 5m, the representative compounds,
      were examined in terms of their physiological stabilities and pharmacokinetics.
      Compound 5d showed good stability in PBS and simulated intestinal fluid, and an
      analysis of its pharmacokinetics in mice suggested that the introduction of an
      amide group to gemcitabine could greatly improve its bioavailability. Further
      evaluation of compound 5d in vivo showed that this compound possesses higher
      activity than gemcitabine against the growth of HepG2 human hepatocellular
      carcinoma cells and HCT-116 colon adenocarcinoma cells with less toxicity to
      animals. These results suggest that compound 5d could be further developed as a
      potential oral anticancer agent for clinical applications in which gemcitabine is
      currently used.

PMID- 22642667
TI  - In vitro and in vivo characterization and strain safety of  Lactobacillus reuteri
      NCIMB 30253 for probiotic applications.
AB  - Lactobacillus reuteri  NCIMB 30253 was shown to have potential as a probiotic by
      reducing the proinflammatory chemokine interleukin-8. Moreover, this strain was
      evaluated, by in vitro and in vivo techniques, for its safety for human
      consumption. The identity of the strain was investigated by metabolic profiling
      and 16S rRNA gene sequencing, and in vitro safety evaluations were performed by
      molecular and metabolic techniques. Genetic analysis was confirmed by assessing
      the minimum inhibitory concentration to a panel of antibiotics, showing that the
      strain was susceptible to 8 antibiotics tested. The ability of the strain to
      produce potentially harmful by-products and antimicrobial compounds was
      evaluated, showing that the strain does not produce biogenic amines and does not
      show bacteriocin activity or reuterin production. A 28-day repeated oral dose
      study was conducted in normal Sprague-Dawley rats to support the in vivo strain
      safety. Oral administration of the strain resulted in no changes in general
      condition and no clinically significant changes to biochemical and haematological
      markers of safety relative to vehicle control treated animals. This comprehensive
      assessment of safety of L. reuteri NCIMB 30253 supports the safety of the strain
      for use as a probiotic.

PMID- 22642668
TI  - Body plethysmographic study of specific airway resistance in a sample of healthy
      adults.
AB  - BACKGROUND AND OBJECTIVE: sRaw (specific airway resistance) is a corrected index
      (Raw multiplied by thoracic gas volume) that describes airway behaviour
      regardless of lung volume. Normal values of sRaw in adult subjects have never
      been formally defined. To establish sRaw interpretation criteria and to define a
      range of reference values, we evaluated variability, reproducibility and
      reliability of sRaw measurements in a group of healthy adults. METHODS: We
      analysed 517 subjects of both genders, aged 18-65 (group A), and to assess the
      reproducibility of the measurements, we investigated intra-individual variation
      and potential daily and weekly sRaw rhythms in a subgroup of 18 co-operative
      healthy subjects (group B). RESULTS: In group A, there was no pattern of
      association between any of the considered anthropometric parameters; mean sRaw
      was higher in men (6.24 vs.5.95 cmH2O s in females; P = 0.0128), but when the
      data were stratified by age, gender-related differences were only found in the
      group aged 46-60 (males 6.45 cmH2O s, females 6.01 cmH2O s; P = 0.0219). In group
      B, there was no statistically significant, time-dependent variation during the
      single tests, nor any circadian or weekly rhythm. CONCLUSIONS: sRaw is a reliable
      parameter; therefore, we propose that the lower and upper 95% confidence limits
      should be considered as reference values for adults of both genders, regardless
      of age. The availability of reference values may be useful in clinical practice
      and research.

PMID- 22642669
TI  - Enhanced Cu2S/CdS coaxial nanowire solar cells by piezo-phototronic effect.
AB  - Nanowire solar cells are promising candidates for powering nanosystems and
      flexible electronics. The strain in the nanowires, introduced during growth,
      device fabrication and/or application, is an important issue for piezoelectric
      semiconductor (like CdS, ZnO, and CdTe) based photovoltaic. In this work, we
      demonstrate the first largely enhanced performance of n-CdS/p-Cu(2)S coaxial
      nanowire photovoltaic (PV) devices using the piezo-phototronics effect when the
      PV device is subjected to an external strain. Piezo-phototronics effect could
      control the electron-hole pair generation, transport, separation, and/or
      recombination, thus enhanced the performance of the PV devices by as high as 70%.
      This effect offers a new concept for improving solar energy conversation
      efficiency by designing the orientation of the nanowires and the strain to be
      purposely introduced in the packaging of the solar cells. This study shed light
      on the enhanced flexible solar cells for applications in self-powered technology,
      environmental monitoring, and even defensive technology.

PMID- 22642670
TI  - Recent advances in mechanical characterisation of biofilm and their significance
      for material modelling.
AB  - In recent years, the advances in microbiology show that biofilms are structurally
      complex, dynamic and adaptable systems including attributes of multicellular
      organisms and miscellaneous ecosystems. One may distinguish between beneficial
      and harmful biofilms appearing in daily life as well as various industrial
      processes. In order to advance the growth of the former or prevent the latter
      type of biofilm, a detailed understanding of its properties is indispensable.
      Besides microbiological aspects, this concerns the determination of mechanical
      characteristics, which provides the basis for material modelling. In the present
      paper the existing experimental methods that have been proposed since the 1980s
      are reviewed and critically discussed with respect to their usefulness and
      applicability to develop numerical modelling approaches.

PMID- 22642671
TI  - Effects of the hedgehog inhibitor GDC-0449, alone or in combination with
      dasatinib, on BCR-ABL-positive leukemia cells.
AB  - Hedgehog (Hh)-glioma-associated oncogene homolog (Gli) signaling is implicated in
      a large number of human cancers such as leukemia. In this study, we investigated
      the effects of the potent Hh antagonist GDC-0449 on the BCR-ABL-positive cell
      line OM9;22 and primary samples when leukemia cells were protected by a feeder
      cell line (S9 cells). The numbers of OM9;22 cells significantly increased with S9
      cells. Treatment of OM9;22 cells with GDC-0449 caused cell growth inhibition and
      induced apoptosis. Moreover, GDC-0449 inhibited the colony growth of Philadelphia
      chromosome (Ph)-positive primary samples. We next investigated the effects of a
      combination of GDC-0449 and dasatinib on these cell lines. The growth inhibition
      typically promoted by dasatinib was significantly reduced in the presence of S9
      cells. Treatment of Ph-positive leukemia cells with GDC-0449 and dasatinib in the
      presence of S9 caused significantly more cytotoxicity than that caused by each
      drug alone. Inhibition of Gli1 or Gli2 by siRNA transfection reduced the growth
      of the Ph-positive cell line K562 and increased cytotoxicity of dasatinib.
      Moreover, colony formations of Gli1 or Gli2 knockdown cells were also reduced.
      Data from this study suggest that administration of the Hh inhibitor GDC-0449
      inhibits BCR-ABL-positive cell growth and enhances the cytotoxic effects of
      dasatinib in the presence of feeder cells.

PMID- 22642672
TI  - Changes in attention to relevant and irrelevant stimuli during spatial learning.
AB  - Rats were trained in 2 experiments to find a submerged platform that was situated
      in 1 of 2 of the 4 corners of a rectangular pool with a curved long wall.
      Different landmarks occupied 2 of the corners on every trial, and the platform
      was always situated near a landmark. For the place group in each experiment, the
      location of the platform was indicated by the shape of the pool and stimuli
      outside the pool (place cues), but not the landmarks within the pool. For the
      landmark groups, the landmarks, not the place cues, indicated where the platform
      could be found. During Stage 2, 2 of the place cues were relevant, and 2 of the
      landmarks were irrelevant, for a new discrimination. The place cues better
      controlled searching for the platform in the place group than in the landmark
      group when the place cues had initially been relevant by signaling the presence
      (Experiment 1) or the absence (Experiment 2) of the platform. The results show
      that animals pay more attention to relevant than irrelevant cues.

PMID- 22642673
TI  - Generalization of contextual fear as a function of familiarity: the role of
      within- and between-context associations.
AB  - Three experiments in rats investigated the generalization of conditioned fear
      from one context (B) to both a preexposed context (A) and a novel context (C). In
      each experiment, when the conditioning context (B) had been preexposed, there was
      greater generalization to context A than to context C; but when B was novel at
      the outset of conditioning this difference between A and C was not observed. The
      implications of these results for associative treatments of the development of
      contextual memories are evaluated.

PMID- 22642676
TI  - Maternal sensitivity and children's behavior problems: examining the moderating
      role of infant sleep duration.
AB  - The current study aimed to examine infant sleep duration as a moderator of the
      relations between maternal sensitivity and child externalizing and internalizing
      symptoms, in a prospective longitudinal design. Fifty-five Caucasian infants (33
      girls) took part in 2 assessments, at 1 and 4 years. Maternal sensitivity was
      rated at 1 year, based on observations performed throughout a home visit. Infant
      sleep duration (i.e., nighttime sleep duration and 24-hr sleep duration) was
      assessed at 1 year as well, using a sleep diary completed by mothers. At 4 years,
      mothers completed the Child Behavior Checklist to assess children's internalizing
      and externalizing symptoms. Results indicated that maternal sensitivity
      interacted with infant nighttime sleep duration, such that there were negative
      relations between sensitivity and subsequent internalizing and externalizing
      symptoms only for children who slept more at night. Interactions using 24-hr
      sleep duration as the moderator were not significant. These findings add to an
      emerging literature on the importance of sleep for children's daytime functioning
      by suggesting that inadequate or insufficient sleep in infancy can interfere with
      the normal developmental process linking early maternal sensitivity to child
      subsequent emotional and behavioral adjustment.

PMID- 22642675
TI  - Monoaminergic modulation of photoreception in ascidian: evidence for a proto
      hypothalamo-retinal territory.
AB  - BACKGROUND: The retina of craniates/vertebrates has been proposed to derive from
      a photoreceptor prosencephalic territory in ancestral chordates, but the
      evolutionary origin of the different cell types making the retina is disputed.
      Except for photoreceptors, the existence of homologs of retinal cells remains
      uncertain outside vertebrates. METHODS: The expression of genes expressed in the
      sensory vesicle of the ascidian Ciona intestinalis including those encoding
      components of the monoaminergic neurotransmission systems, was analyzed by in
      situ hybridization or in vivo transfection of the corresponding regulatory
      elements driving fluorescent reporters. Modulation of photic responses by
      monoamines was studied by electrophysiology combined with pharmacological
      treatments. RESULTS: We show that many molecular characteristics of dopamine
      synthesizing cells located in the vicinity of photoreceptors in the sensory
      vesicle of the ascidian Ciona intestinalis are similar to those of amacrine
      dopamine cells of the vertebrate retina. The ascidian dopamine cells share with
      vertebrate amacrine cells the expression of the key-transcription factor Ptf1a,
      as well as that of dopamine-synthesizing enzymes. Surprisingly, the ascidian
      dopamine cells accumulate serotonin via a functional serotonin transporter, as
      some amacrine cells also do. Moreover, dopamine cells located in the vicinity of
      the photoreceptors modulate the light-off induced swimming behavior of ascidian
      larvae by acting on alpha2-like receptors, instead of dopamine receptors,
      supporting a role in the modulation of the photic response. These cells are
      located in a territory of the ascidian sensory vesicle expressing genes found
      both in the retina and the hypothalamus of vertebrates (six3/6, Rx, meis, pax6,
      visual cycle proteins). CONCLUSION: We propose that the dopamine cells of the
      ascidian larva derive from an ancestral multifunctional cell population located
      in the periventricular, photoreceptive field of the anterior neural tube of
      chordates, which also gives rise to both anterior hypothalamus and the retina in
      craniates/vertebrates. It also shows that the existence of multiple cell types
      associated with photic responses predates the formation of the vertebrate retina.

PMID- 22642677
TI  - Orbital glomangioma.
AB  - Glomangioma is a vascular hamartomatous tumor originating from the glomus body, a
      specialized thermoregulatory organ localized in the dermis and precoccygeal soft
      tissue. Glomus tumors are characteristically found in the hands and are very
      rarely reported in the head region. Here we describe a 29-year-old woman
      presenting with acute proptosis and pain in the left eye. A computed tomography
      scan of the orbit revealed a well-defined circumscribed mass, displacing the
      globe and lateral rectus muscle inferotemporally. The tumour was surgically
      removed through a lateral Kronlein approach. On histology, the lesion consisted
      of cavernous vascular spaces, partly filled with blood and thrombotic material,
      and a mixture of capillary-sized vessels and tumor cells; immunostaining for
      smooth actin showed a strong positivity in the cytoplasm of tumor cells,
      consistent with a diagnosis of glomangioma. Our case adds to the very few cases
      of orbital glomangioma reported in the literature and demonstrates that this
      tumor can be safely removed.

PMID- 22642678
TI  - Palladium-catalyzed carbonylation of aryl, alkenyl, and allyl halides with phenyl
      formate.
AB  - Highly efficient palladium-catalyzed carbonylation of aryl, alkenyl, and allyl
      halides with phenyl formate is reported. This procedure does not use carbon
      monoxide and affords one-carbon-elongated carboxylic acid phenyl esters in
      excellent yields. The reaction proceeds smoothly under mild conditions and
      tolerates a wide range of functional groups including aldehyde, ether, ketone,
      ester, and cyano groups. Furthermore, a variety of heteroaromatic bromides can be
      converted to the corresponding phenyl esters in high yields.

PMID- 22642679
TI  - Evaluating physical functioning as part of a Cognitive Behavioural Therapy
      approach in treatment of people suffering from chronic pain.
AB  - AIMS AND OBJECTIVES: To evaluate physical functioning in a nurse-led integrated
      physiotherapy and Cognitive Behavioural Therapy (CBT) approach in treatment of
      people suffering from chronic pain. BACKGROUND: Inter-professional working and
      physical activity supervision is described as important components of successful
      rehabilitation and is often included in approaches to chronic pain. DESIGN: A
      quasi-experimental nonrandomised controlled design was used. METHOD: A
      consecutive sample of 117 outpatients from a rehabilitation unit at a university
      hospital was included in this intervention study. The effects of an 8-week
      multidisciplinary programme, including 6 and 12 month follow-up, was examined
      with measures including health-related quality of life (HRQL), pain perception,
      pain stages of change and physical functioning. To broaden our understanding
      qualitative data from three physiotherapists involved were collected. RESULTS:
      Improvements in physical functioning status during the programme were positively
      related to improvements in stages of change, pain interference (PI) and severity
      (PS) and HRQL. Qualitative data support these findings. CONCLUSIONS: Findings
      suggest that our pain management intervention, that includes physical activity
      designed to help patients to live a healthier life, can have a clinically
      assessable impact on reducing PI and PS, improving physical functioning and HRQL.
      RELEVANCE TO CLINICAL PRACTICE: Training in CBT approaches and inter-professional
      working in chronic pain may extend the skills of nurses and physiotherapists to
      improve physical functioning among a group of patients for whom traditional
      medicine has little to offer.

PMID- 22642680
TI  - Growth stimulating effect on queen bee larvae of histone deacetylase inhibitors.
AB  - Royal jelly (RJ) is a widely used natural food. It is also a major source of
      nutrition for queen bees and plays a key role in their development. RJ is
      secreted from the hypopharyngeal and mandibular glands of young adult worker
      bees. The regulation of gene expression in these two glands may influence the
      development of queen bees by affecting the content of RJ. This study investigated
      the epigenetic effects in these two glands in young adult worker bees treated
      with histone deacetylase inhibitors (HDACis), a U.S. Food and Drug Administration
      approved drug, suberoylanilide hydroxamic acid (SAHA), and NBM-HD-1, a novel
      compound synthesized in this laboratory. Western blot analyses indicated that the
      levels of acetyl-histone 3 and p21 protein expression in MCF-7 cells increased
      markedly after treatment with NBM-HD-1. The data proved that NBM-HD-1 was a novel
      and potent HDACi. Furthermore, a method of affecting epigenetic regulation of the
      mrjp family gene in the hypopharyngeal and mandibular glands of young adult
      worker bees was developed by feeding young adult worker bees HDACi. Epigenetic
      regulation produced several important biological effects. A marked change in the
      protein composition of the RJ secreted from these treated bees was found. Only
      the ratio of specific major royal jelly protein 3 (MRJP3) was significantly
      altered in the treated bees versus the untreated controls. Other MRJP family
      proteins did not change. This alteration in the ratio of royal jelly proteins
      resulted in a significant increase in the body size of queen bee larvae. The data
      seem to suggest that HDACis may play an important role in the epigenetic
      regulation of the hypopharyngeal and mandibular glands of young adult worker
      bees. They appear to change mrjp3 gene expression and alter the ratio of MRJP3
      protein in RJ. This study presents the first evidence that HDACis are capable of
      regulating the ratio of MRJP3 proteins in RJ, which has the potential to change
      the body size of queen bees during their development.

PMID- 22642681
TI  - Patterns of toxicity and factors influencing severity in acute adult trimipramine
      poisoning.
AB  - AIMS: To analyze the clinical features of trimipramine poisoning, identify a
      minimal toxic dose, and the dose bearing a 50% risk of developing a moderate,
      severe or fatal outcome. METHODS: All acute adult trimipramine monointoxications
      reported by physicians to the Swiss Toxicological Information Centre between
      January 1992 and December 2009 were identified. RESULTS: Two hundred and thirty
      cases (26 confirmed and 204 probable) were analyzed, the mean age was 35.7 years
      and 74% were females. One hundred and thirty-seven patients showed mild, 54
      moderate and 21 severe symptoms. Three cases were fatal due to refractory
      cardiovascular collapse. Ninety-three per cent of the events were attempted or
      completed suicides. The most common symptoms were central nervous system
      depression (79.2%), tachycardia (19.1%) and QT(c) prolongation (13.9%). The
      severity of poisoning depended significantly on the ingested dose (P < 0.001).
      The minimal dose for moderate symptoms was 250 mg (median dose 1.2 g) and 850 mg
      for severe symptoms (median dose 2.7 g). The dose for a 50% risk of developing a
      moderate, severe or fatal outcome was 5.11 g. In 38 patients early
      gastrointestinal decontamination was performed. Overall, these patients ingested
      higher trimipramine doses than the late- or not-decontaminated patients (P =
      0.113). The median doses were also higher in the decontaminated group within each
      severity category except in the fatal cases. CONCLUSIONS: We demonstrated that
      moderate trimipramine poisoning can already occur after ingestion of doses in the
      high therapeutic range. Poisoned patients have to be monitored for central
      nervous system depression, dysrhythmias and QT(c) prolongation. Early
      decontamination might be beneficial.

PMID- 22642682
TI  - Origin of long-lived coherences in light-harvesting complexes.
AB  - A vibronic exciton model is applied to explain the long-lived oscillatory
      features in the two-dimensional (2D) electronic spectra of the Fenna-Matthews
      Olson (FMO) complex. Using experimentally determined parameters and uncorrelated
      site energy fluctuations, the model predicts oscillations with dephasing times of
      1.3 ps at 77 K, which is in a good agreement with the experimental results. These
      long-lived oscillations originate from the coherent superposition of vibronic
      exciton states with dominant contributions from vibrational excitations on the
      same pigment. The oscillations obtain a large amplitude due to excitonic
      intensity borrowing, which gives transitions with strong vibronic character a
      significant intensity despite the small Huang-Rhys factor. Purely electronic
      coherences are found to decay on a 200 fs time scale.

PMID- 22642683
TI  - Determinants of delayed detection of cancers in Texas counties in the United
      States of America.
AB  - INTRODUCTION: Previous studies have shown that delayed detection of several
      cancers is related to socioeconomic deprivation as measured by the Wellbeing
      Index (WI) in Texas, the United States of America (USA). The current study
      investigates whether delayed cancer detection is related to lack of health
      insurance, physician shortage and higher percentages of Hispanics rather than WI
      per se since these factors are directly related to delayed cancer detection and
      may confound WI. METHODS: Cancer data and potential determinants of delayed
      cancer detection are derived from Texas Cancer Registry, Texas State Data Center,
      and Texas Department of State Health Services and U.S. Census Bureau. Texas
      cancer data from 1997 to 2003 are aggregated to calculate age-adjusted late- and
      early-stage cancer detection rates. The WI for each county is computed using data
      from the USA Census 2000. A weighted Tobit regression model is used to account
      for population size and censoring. The percentage of late-stage cancer cases is
      the dependent variable while independent variables include WI and the
      aforementioned potential confounders. RESULTS: Delayed detection of breast, lung,
      colorectal and female genital cancers is associated with higher percentage of
      uninsured residents (p < 0.05). Delayed detection is also associated with
      physician shortage and lower percentages of Hispanics for certain cancers ceteris
      paribus ( p < 0.05). The percentage of late-stage cases is positively correlated
      with WI for lung, and prostate cancers after adjusting for confounders ( p <
      0.05). CONCLUSIONS: The percentages of uninsured and Hispanic residents as well
      as physician supply are determinants of delayed detection for several cancers
      independently of WI, and vice versa. Identification of these determinants
      provides the evidence-base critical for decision makers to address specific
      issues for promoting early detection in effective cancer control.

PMID- 22642684
TI  - Selective production of acetone during continuous synthesis gas fermentation by
      engineered biocatalyst Clostridium sp. MAceT113.
AB  - AIMS: To engineer acetogen biocatalyst capable of fermenting synthesis gas blend
      to acetone as the only liquid carbonaceous product. METHODS AND RESULTS: The
      metabolic engineering comprised inactivation of phosphotransacetylase via
      integration of a cassette comprising synthetic genes erm(B), thiolase and HMG-CoA
      synthase. Acetaldehyde dehydrogenase was inactivated via integration of a
      cassette consisting of synthetic genes cat, HMG-CoA lyase and acetoacetate
      decarboxylase. The engineered biocatalyst Clostridum sp. MAceT113 lost production
      of 253 mmol l(-1) ethanol and 296 mmol l(-1) acetate and started producing 1.8
      mol l(-1) acetone in single-stage continuous syngas fermentation. CONCLUSIONS:
      The acetone concentration in culture broth is economical for bulk manufacture
      because it is about twenty times of that achieved with known acetone-butanol
      ethanol fermentation of sugars. SIGNIFICANCE AND IMPACT OF THE STUDY: The process
      shows the opportunity to produce acetone from synthesis gas at concentrations
      comparable with production of acetone from products of petroleum cracking. This
      is the first report on elimination of acetate and acetaldehyde production and
      directing carbon flux from Acetyl-CoA to acetone via a non-naturally occurring in
      acetogen acetone biosynthesis pathway identified in eukaryotic organisms.

PMID- 22642685
TI  - Protective efficacy of a  Mycoplasma pneumoniae  P1C DNA vaccine fused with the B
      subunit of  Escherichia coli  heat-labile enterotoxin.
AB  - In the present study, we investigated the immunomodulatory responses of a DNA
      vaccine constructed by fusing Mycoplasma pneumoniae P1 protein carboxy terminal
      region (P1C) with the Escherichia coli heat-labile toxin B subunit (LTB). BALB/c
      mice were immunized by intranasal inoculation with control DNAs, the P1C DNA
      vaccine or the LTB-P1C fusion DNA vaccine. Levels of the anti-M. pneumoniae
      antibodies and levels of interferon-gamma and IL-4 in mice were increased
      significantly upon inoculation of the LTB-P1C fusion DNA vaccine when compared
      with the inoculation with P1C DNA vaccine. The LTB-P1C fusion DNA vaccine
      efficiently enhanced the M. pneumoniae-specific IgA and IgG levels. The
      IgG2a/IgG1 ratio was significantly higher in bronchoalveolar lavages fluid and
      sera from mice fusion with LTB and P1C than mice receiving P1C alone. When the
      mice were challenged intranasally with 10(7) CFU M. pneumoniae strain (M129), the
      LTB-P1C fusion DNA vaccine conferred significantly better protection than P1C DNA
      vaccine (P < 0.05), as suggested by the results, such as less inflammation, lower
      histopathological score values, lower detectable number of M. pneumoniae strain,
      and lower mortality of challenging from 5 * 10(8) CFU M. pneumoniae. These
      results indicated that the LTB-P1C fusion DNA vaccine efficiently improved
      protective efficacy against M. pneumoniae infection and effectively attenuated
      development of M. pneumoniae in mice.

PMID- 22642686
TI  - Strength training reduces intracortical inhibition.
AB  - AIM: Paired-pulse transcranial magnetic stimulation was used to investigate the
      influence of 4 weeks of heavy load squat strength training on corticospinal
      excitability and short-interval intracortical inhibition (rectus femoris muscle).
      METHODS: Participants (n = 12) were randomly allocated to a strength training or
      control group. The strength training group completed 4 weeks of heavy load squat
      strength training. Recruitment curves were constructed to determine values for
      the slope of the curve, V50 and peak height. Short-interval intracortical
      inhibition was assessed using a subthreshold (0.7 * active motor threshold)
      conditioning stimulus, followed 3 ms later by a supra-threshold (1.2 * active
      motor threshold) test stimulus. All motor evoked responses were taken during 10%
      of maximal voluntary isometric contraction (MVC) torque and normalized to the
      maximal M-wave. RESULTS: The strength training group attained 87% increases in
      1RM squat strength (P < 0.01), significant increases in measures of corticospinal
      excitability (1.2 * Motor threshold: 116%, P = 0.016; peak height of recruitment
      curve = 105%, P < 0.001), and a 32% reduction in short-interval intracortical
      inhibition (P < 0.01) following the 4-week intervention compared with control.
      There were no changes in any dependent variable (P > 0.05) detected in the
      control group. CONCLUSION: Repeated high force voluntary muscle activation in the
      form of short-term strength training reduces short-interval intracortical
      inhibition. This is consistent with studies involving skilled/complex tasks or
      novel movement patterns and acute studies investigating acute voluntary
      contractions.

PMID- 22642687
TI  - Glycogen synthase kinase-3 inhibition promotes proliferation and neuronal
      differentiation of human-induced pluripotent stem cell-derived neural
      progenitors.
AB  - Human-induced pluripotent stem cell-derived neural progenitors (hiPSC-NPs) have
      the ability to self-renew and differentiate into glial and neuronal lineages,
      which makes them an invaluable source in cell replacement therapy for
      neurological diseases. Therefore, their enhanced proliferation and neuronal
      differentiation are pivotal features that can be used in repairing neurological
      injuries. One of the main regulators of neural development is Wnt signaling,
      which results in the inhibition of glycogen synthase kinase 3 (GSK-3). Here, we
      assess the impact of GSK-3 inhibition by the small molecule CHIR99021 on the
      expansion and differentiation of hiPSC-NPs in an adherent condition and a defined
      medium. Cell proliferation analyses have revealed that inhibition of GSK-3 in the
      presence of epidermal growth factor (EGF) and basic fibroblast growth factor
      (bFGF) increased the proliferation of hiPSC-NPs across 10 passages. The
      inhibition of beta-catenin signaling by XAV and NOTCH signaling by DAPT reversed
      CHIR impact on hiPSC-NPs proliferation. The target genes of beta-catenin, C-MYC
      and CYCLIN D1 as well as NOTCH target genes, HES1 and HES5 were upregulated. The
      treatment of NPs by CHIR in the absence of bFGF and EGF resulted in an increase
      of neuronal differentiation rather than proliferation by stabilization of beta
      catenin regardless of the NOTCH pathway. Thus, GSK-3 inhibition has been shown to
      promote proliferation of the NPs by activating beta-catenin and NOTCH-related
      cell cycle genes in the presence of bFGF and EGF. Additionally, during GSK-3
      inhibition, an absence of these growth factors allows for the switch to neuronal
      differentiation with a bias toward a dopaminergic fate. This may provide desired
      cells that can be used in therapeutic applications and offer insights into the
      etiology of some neurological disorders.

PMID- 22642688
TI  - An embodiment effect in computer-based learning with animated pedagogical agents.
AB  - How do social cues such as gesturing, facial expression, eye gaze, and human-like
      movement affect multimedia learning with onscreen agents? To help address this
      question, students were asked to twice view a 4-min narrated presentation on how
      solar cells work in which the screen showed an animated pedagogical agent
      standing to the left of 11 successive slides. Across three experiments, learners
      performed better on a transfer test when a human-voiced agent displayed human
      like gestures, facial expression, eye gaze, and body movement than when the agent
      did not, yielding an embodiment effect. In Experiment 2 the embodiment effect was
      found when the agent spoke in a human voice but not in a machine voice. In
      Experiment 3, the embodiment effect was found both when students were told the
      onscreen agent was consistent with their choice of agent characteristics and when
      inconsistent. Students who viewed a highly embodied agent also rated the social
      attributes of the agent more positively than did students who viewed a
      nongesturing agent. The results are explained by social agency theory, in which
      social cues in a multimedia message prime a feeling of social partnership in the
      learner, which leads to deeper cognitive processing during learning, and results
      in a more meaningful learning outcome as reflected in transfer test performance.

PMID- 22642689
TI  - Why are there more arboreal ant species in primary than in secondary tropical
      forests?
AB  - 1. Species diversity of arboreal arthropods tends to increase during rainforest
      succession so that primary forest communities comprise more species than those
      from secondary vegetation, but it is not well understood why. Primary forests
      differ from secondary forests in a wide array of factors whose relative impacts
      on arthropod diversity have not yet been quantified. 2. We assessed the effects
      of succession-related determinants on a keystone ecological group, arboreal ants,
      by conducting a complete census of 1332 ant nests from all trees with diameter at
      breast height >= 5 cm occurring within two (unreplicated) 0.32-ha plots, one in
      primary and one in secondary lowland forest in New Guinea. Specifically, we used
      a novel rarefaction-based approach to match number, size distribution and
      taxonomic structure of trees in primary forest communities to those in secondary
      forest and compared the resulting numbers of ant species. 3. In total, we
      recorded 80 nesting ant species from 389 trees in primary forest but only 42
      species from 295 trees in secondary forest. The two habitats did not differ in
      the mean number of ant species per tree or in the relationship between ant
      diversity and tree size. However, the between-tree similarity of ant communities
      was higher in secondary forest than in primary forest, as was the between-tree
      nest site similarity, suggesting that secondary trees were more uniform in
      providing nesting microhabitats. 4. Using our rarefaction method, the difference
      in ant species richness between two forest types was partitioned according to the
      effects of higher tree density (22.6%), larger tree size (15.5%) and higher
      taxonomic diversity of trees (14.3%) in primary than in secondary forest. The
      remaining difference (47.6%) was because of higher beta diversity of ant
      communities between primary forest trees. In contrast, difference in nest density
      was explained solely by difference in tree density. 5. Our study shows that
      reduction in plant taxonomic diversity in secondary forests is not the main
      driver of the reduction in canopy ant species richness. We suggest that the
      majority of arboreal species losses in secondary tropical forests are
      attributable to simpler vegetation structure, combined with lower turnover of
      nesting microhabitats between trees.

PMID- 22642690
TI  - Diet, occupational exposure and early asthma incidence among bakers, pastry
      makers and hairdressers.
AB  - BACKGROUND: The natural history of occupational asthma (OA) is influenced by many
      determinants. This study aims to assess the combined roles of personal
      characteristics, including occupational exposure and nutritional habits, on the
      incidence of OA during the first years at work. METHODS: A nested case-control
      study was conducted within a retrospective cohort of young workers in the bakery,
      pastry-making and hairdressing sectors. Cases were subjects diagnosed as
      'confirmed' or 'probable' OA consecutively to a medical visit (N = 31). Controls
      were subjects without OA (N = 196). Atopy was defined after blood specific IgE
      analysis, based on the PhadiatopTM test. Occupational exposure was characterized
      by standardized questionnaires and diet patterns by a food frequency
      questionnaire. RESULTS: Among bakers and pastry-makers, only atopy is an
      independent risk factor of OA (OR = 10.07 95%CI [2.76 - 36.65]). Among
      hairdressers, several variables are associated with OA. Body mass index (unit OR
      = 1.24 [1.03 - 1.48]) and the score of exposure intensity (unit OR = 1.79 [1.05 -
      3.05]) are independent predictors of OA, but the role of atopy is weak (OR = 4.94
      [0.66 - 36.75]). Intake of vitamin A is higher among hairdressers cases (crude p
      = 0.002, adjusted p = 0.01 after control for body mass index and atopy); the same
      observation is made for vitamin D (crude p = 0.004, adjusted p = 0.01).
      CONCLUSION: This study suggests that the influence of several factors on the
      incidence of OA, including dietary vitamins, might vary across exposure settings.

PMID- 22642692
TI  - Examining the health information-seeking behaviors of Korean Americans.
AB  - Many Korean Americans suffer from high levels of cancer incidence and have low
      cancer screening rates. A significant number of Korean Americans lack adequate
      information about cancer screening tests. However, little is known about their
      health behaviors. This article examines exposure to mass media and health
      information-seeking behaviors for Korean Americans, and their associations with
      demographic characteristics influencing variations in exposure to the different
      health information and trust in health information sources. The authors gathered
      data for this study using a cross-sectional, community-based survey conducted in
      the Washington, DC, metropolitan area during 2006 and 2007. It was administered
      to 254 Korean Americans who were 40 years of age or older. This study is part of
      the first health-related program of research to study exposure to mass media,
      health and cancer information sources, and seeking preferences and experiences of
      Korean Americans. Results indicated that Korean ethnic media sources and Internet
      are important sources used regularly. Age, years of education completed, and
      English proficiency levels for Korean Americans significantly predicted the
      likelihood of their Internet use. Low-income Korean Americans with less education
      were more likely to seek health information in Korean ethnic magazines and
      newspapers, whereas Korean Americans with higher education and English
      proficiency were more likely to seek information online. The most trusted source
      of health information among respondents was from a doctor or other health care
      professional. Future research should be conducted to determine whether physicians
      are actually used as a primary source for health information.

PMID- 22642693
TI  - Prenylation of a nonaromatic carbon of indolylbutenone by a fungal indole
      prenyltransferase.
AB  - FtmPT1 from Aspergillus fumigatus is a fungal indole prenyltransferase (PT) that
      normally catalyzes the regiospecific prenylation of brevianamide F (cyclo-L-Trp-L
      Pro) at the C-2 position of the indole ring with dimethylallyl diphosphate
      (DMAPP). Interestingly, FtmPT1 exhibited remarkable substrate tolerance and
      accepted (E)-4-(1H-indol-3-yl)but-3-en-2-one (1) as a substrate to produce an
      unnatural novel alpha-prenylindolylbutenone (1a). This is the first demonstration
      of the prenylation of a nonaromatic carbon of the acceptor substrate by a fungal
      indole PT.

PMID- 22642694
TI  - Electric-field-dependent photoconductivity in CdS nanowires and nanobelts:
      exciton ionization, Franz-Keldysh, and Stark effects.
AB  - We report on the electric-field-dependent photoconductivity (PC) near the band
      edge region of individual CdS nanowires and nanobelts. The quasi-periodic
      oscillations above the band edge in nanowires and nanobelts have been attributed
      to a Franz-Keldesh effect. The exciton peaks in PC spectra of the nanowires and
      thinner nanobelts show pronounced red-shifting due to the Stark effect as the
      electric field increases, while the exciton ionization is mainly facilitated by
      strong electron-longitudinal optical (LO) phonon coupling. However, the band-edge
      transition of thick nanobelts blue-shifts due to the field-enhanced exciton
      ionization, suggesting partial exciton ionization as the electron-LO phonon
      coupling is suppressed in the thicker belts. Large Stark shifts, up to 48 meV in
      the nanowire and 12 meV in the thinner nanobelts, have been achieved with a
      moderate electric field on the order of kV/cm, indicating a strong size and
      dimensionality implication due to confinement and surface depletion.

PMID- 22642691
TI  - Reporting recommendations for tumor marker prognostic studies (REMARK):
      explanation and elaboration.
AB  - BACKGROUND: The Reporting Recommendations for Tumor Marker Prognostic Studies
      (REMARK) checklist consists of 20 items to report for published tumor marker
      prognostic studies. It was developed to address widespread deficiencies in the
      reporting of such studies. In this paper we expand on the REMARK checklist to
      enhance its use and effectiveness through better understanding of the intent of
      each item and why the information is important to report. METHODS: REMARK
      recommends including a transparent and full description of research goals and
      hypotheses, subject selection, specimen and assay considerations, marker
      measurement methods, statistical design and analysis, and study results. Each
      checklist item is explained and accompanied by published examples of good
      reporting, and relevant empirical evidence of the quality of reporting. We give
      prominence to discussion of the 'REMARK profile', a suggested tabular format for
      summarizing key study details. SUMMARY: The paper provides a comprehensive
      overview to educate on good reporting and provide a valuable reference for the
      many issues to consider when designing, conducting, and analyzing tumor marker
      studies and prognostic studies in medicine in general. To encourage dissemination
      of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK):
      Explanation and Elaboration, this article has also been published in PLoS
      Medicine.

PMID- 22642695
TI  - Influence of the environment on the protective effects of guaiacol derivatives
      against oxidative stress: mechanisms, kinetics, and relative antioxidant
      activity.
AB  - The peroxyl radical scavenging activity of five guaiacol derivatives (GD) has
      been studied in nonpolar and aqueous solutions, using the density functional
      theory. The studied GD are guaiacol, vanillin, vanillic alcohol, vanillic acid,
      and eugenol. It was found that the environment plays an important role in the
      peroxyl scavenging activity of these compounds. They were all found to react
      faster in aqueous solution than in nonpolar media. The order of reactivity in
      nonpolar environments was found to be vanillic alcohol > eugenol > guaiacol >
      vanillin > vanillic acid, while, in aqueous solution, at physiological pH, it
      becomes vanillic acid > vanillic alcohol > guaiacol ~ eugenol > vanillin. It was
      also found that in aqueous solution as the pH increases so does the reactivity of
      GD toward peroxyl radicals. The environment also has important effects on the
      relative importance of the hydrogen transfer (HT) and the sequential proton
      electron transfer (SPET) mechanisms, which are the ones relevant to the peroxyl
      radical scavenging activity of GD. The HT from the phenolic OH was identified as
      the main scavenging process in nonpolar media, and in aqueous solution at pH <=
      4. On the other hand, SPET is proposed to be the one contributing the most to the
      overall peroxyl scavenging activity of GD in aqueous solution at pH >= 6.

PMID- 22642696
TI  - Acute orbital inflammatory syndrome secondary to an ANCA-positive small-vessel
      vasculitis: a case report and review of the literature.
AB  - A 61-year-old man presents with sequential painful bilateral proptosis within 36
      h and orbital compartment syndrome resulting in complete loss of vision
      bilaterally. Sequential urgent lateral canthotomy and cantholysis were performed
      to reverse the compartment syndrome. Orbital imaging showed non-specific orbital
      inflammation. Biopsies showed necrotizing inflammation and bloodwork was positive
      for c-ANCA. The patient was therefore treated with prednisone and
      cyclophosphomide and showed good recovery of vision in one eye, and had no
      recurrence of orbital inflammation. ANCA-associated orbital vasculitides are
      rare, but must be kept in mind in the differential diagnosis of acute orbital
      inflammatory syndromes.

PMID- 22642698
TI  - Sediment records of polycyclic aromatic hydrocarbons (PAHs) in the continental
      shelf of China: implications for evolving anthropogenic impacts.
AB  - Sources, compositions, and historical records of polycyclic aromatic hydrocarbons
      (PAHs) in sediment cores collected from the Yellow Sea and the South China Sea
      were analyzed to investigate the influence of anthropogenic activities. The
      occurrence of PAHs was mainly derived from various combustion sources, especially
      the combustion of biomass and domestic coal. Uniform composition of sedimentary
      PAHs (52-62% of phenanthrene, benzo[b]fluoranthene, indeno[1,2,3-cd]pyrene, and
      benzo[g,h,i]perylene) suggested air-borne mixtures intractable to degradation.
      The concentrations of the sum of 15 PAHs (16 priority pollutants designed by the
      United States Environmental Protection Agency minus naphthalene; designed as
      Sigma(15)PAH) in Yellow Sea sediment cores were generally higher than those in
      the South China Sea. The profiles of Sigma(15)PAH concentrations recorded in the
      sediment cores closely followed historical socioeconomic development in China. In
      general, Sigma(15)PAH concentrations started to increase from the background
      pollution level posed by agricultural economy at the turn of 20th century. In
      addition, a Sigma(15)PAH concentration reduction was observed during the Chinese
      Civil War (1946-1949) and Great Cultural Revolution (1966-1976), suggesting them
      as setbacks for economic development in Chinese history. Increasing PAH emissions
      as a result of increasing coal combustion associated with the rapid urbanization
      and industrialization since the implementation of the Reform and Open Policy
      (since 1978) accounted for the fast growth of Sigma(15)PAH concentrations in
      sediment cores. The decline of Sigma(15)PAH concentrations from subsurface
      maximum until sampling time was inconsistent with current-day economic
      development in China, and may possibly suggest emission reductions due to
      decreasing proportional use of domestic coal and increasing consumption of
      cleaner energies (natural gas and liquefied petroleum gas).

PMID- 22642697
TI  - The effect of CYP3A inhibitors and inducers on the pharmacokinetics of telaprevir
      in healthy volunteers.
AB  - AIM: To evaluate the effects of ketoconazole, rifampicin and efavirenz on the
      pharmacokinetics of telaprevir in healthy volunteers. METHOD: Results from three
      clinical studies are described. (1) Volunteers received a single 750 mg dose
      telaprevir with and without a single 400 mg dose ketoconazole. (2) Volunteers
      received (a) 1250 mg telaprevir followed by three 750 mg doses given every 8 h
      and (b) four 1250 mg telaprevir doses given every 8 h, with a single 400 mg dose
      ketoconazole given with the fourth dose of telaprevir. (3) Volunteers received
      either a single 750 mg dose telaprevir with or without 600 mg once daily
      rifampicin, or 750 mg every 8 h telaprevir with and without 600 mg once daily
      efavirenz. RESULTS: A single 400 mg dose of ketoconazole increased single dose
      telaprevir exposure: the geometric least-squares mean ratio (GLSMR, with 90%
      confidence limits) was 1.24 (1.10, 1.41) for C(max) and 1.62 (1.45, 1.81) for
      AUC(0,infinity). However, after multiple doses of telaprevir, there was no
      discernible effect of ketoconazole on telaprevir exposure. Co-administration of
      rifampicin at steady-state markedly reduced single dose telaprevir exposure with
      GLSMRs of 0.14 (0.11, 0.18) for C(max) and 0.08 (0.07, 0.11) for AUC(0,infinity),
      whereas efavirenz had a smaller effect on telaprevir exposure when both drugs
      were co-administered at steady-state, with GLSMRs of 0.91 (0.81, 1.02) for C(max)
      , 0.53 (0.44, 0.65) for C(min), and 0.74 (0.65, 0.84) for AUC(0,8 h). CONCLUSION:
      CYP3A inducers, rifampicin and efavirenz, can reduce telaprevir exposure to
      varying degrees based on their potency. The effect of ketoconazole as an
      inhibitor of telaprevir metabolism is more pronounced after a single dose of
      telaprevir than after repeated administration.

PMID- 22642700
TI  - Indigenous hospital experiences: a New Zealand case study.
AB  - AIMS AND OBJECTIVES: To explore Maori (Indigenous people of New Zealand)
      experiences of hospitalisation in surgical or medical settings and how these
      might influence length of stay. BACKGROUND: Globally Indigenous peoples with
      histories of colonisation suffer health disparities compared with other groups.
      They experience higher levels of morbidity, premature mortality, lower life
      expectancies and differential access, use and quality of health services. In
      Indigenous communities' negative anecdotal accounts of hospital experiences
      indicate more research is needed about their hospital experiences. DESIGN: A
      Maori (Indigenous) centered approach using case study methodology and three data
      sources: medical-surgical discharge data, interviews with Maori and a literature
      review. METHOD: Using statistical data from the New Zealand Health Information
      Service from 1989-2006, a retrospective interrupted time series design was used
      to examine length of stay for Maori patients in medical and surgical hospital
      settings. Semi-structured interviews with 11 participants identifying as Maori
      who had experienced hospitalisation in a medical or surgical setting were
      transcribed and thematically analysed. A structured review of the research
      literature on Indigenous hospital experiences was also analysed. These data were
      analysed individually, triangulated and interpreted. RESULTS: Maori consistently
      have a shorter average length of stay than non-Maori using public hospitals in
      New Zealand. Marginalisation of Indigenous peoples in public hospitals was
      evident in both the interviews undertaken and the literature reviewed.
      Participants believed hospitals were not conducive to healing and negative
      experiences contributed to decisions to seek an early discharge. CONCLUSIONS:
      Given the disparities in Indigenous health status, health professionals can
      address negative hospitalisation experiences by attending to the quality of care
      delivered and nature of the hospital environment. RELEVANCE TO CINICAL PRACTICE:
      Nurses can play an important role improving health outcome disparities for
      Indigenous peoples linked to health service delivery, especially the delivery of
      culturally responsive and quality nursing care.

PMID- 22642699
TI  - Inhibitory effect of antioxidant-rich marinades on the formation of heterocyclic
      aromatic amines in pan-fried beef.
AB  - The inhibitory effect of antioxidant-rich marinades containing beer and white
      wine (with/without alcohol) alone or mixed with herbs commonly used as meat
      flavoring (garlic, ginger, thyme, rosemary, and red chili pepper) on the
      formation of heterocyclic aromatic amines (HAs) in pan-fried beef was studied.
      Radical-scavenging activity was evaluated by DPPH assay, before the addition of
      meat to the marinade (T0) and after 4 h of meat marinating (T4). At T0, wine with
      herbs possessed the highest scavenging activity (73.5%), followed by wine
      (72.5%), dealcoholized wine with herbs (53.4%), beer and herbs (41.7%),
      dealcoholized wine (39.6%), and beer (25.9%). At T4, a decrease in the radical
      scavenging activity of all marinades was observed, although with a similar
      radical-scavenging profile. All of the six marinades under the study reduced the
      total amount of HAs, keeping meat with good overall sensory quality. Beer
      marinades were more efficient than white wine marinades, and the addition of
      herbs provided a superior inhibitory effect, reducing around 90% of HAs. No
      correlation was observed between radical-scavenging activity of marinades and
      total or individual HAs formation. Herbs explained around 30% of inhibition of
      PhIP formation, whereas alcohol increased PhIP formation.

PMID- 22642701
TI  - Lessons from two cases of anaphylaxis to proton pump inhibitors.
AB  - WHAT IS KNOWN AND OBJECTIVE: Proton pump inhibitors (PPIs), which are widely used
      for the treatment of peptic ulcers and gastroesophageal diseases, reduce both
      basal and stimulated gastric acid secretion by inhibiting the parietal cell
      enzyme H(+)-K(+)-adenosine triphosphatase. There have been several reports of
      hypersensitivity reactions to PPIs but anaphylaxis is very rare. We report on two
      cases of anaphylaxis to PPIs. CASE SUMMARY: Our two interesting and instructive
      cases of anaphylaxis to PPIs relate to the orally disintegrating form of
      lansoprazole and omeprazole. The first patient had taken esomeprazole 20 mg/day
      for 1 month without any side effects before experiencing anaphylaxis to
      lansoprazole. To our knowledge, this is the first report of anaphylaxis to the
      orally disintegrating form of lansoprazole. In the second case, the patient was
      misdiagnosed with penicillin allergy which she suffered from earlier. WHAT IS NEW
      AND CONCLUSION: Physicians need to be more aware of the possibility of
      hypersensitivity to PPIs.

PMID- 22642702
TI  - A spatial and temporal analysis of notifiable gastrointestinal illness in the
      Northwest Territories, Canada, 1991-2008.
AB  - BACKGROUND: This is the first study to describe the geographical and temporal
      distribution of notifiable gastrointestinal illness (NGI) in the Northwest
      Territories (NWT), Canada. Understanding the distribution of NGI in space and
      time is important for identifying communities at high risk. Using data derived
      from the Northwest Territories Communicable Disease Registry (NWT CDR), a number
      of spatial and temporal techniques were used to explore and analyze NGI incidence
      from the years 1991 to 2008. Relative risk mapping was used to investigate the
      variation of disease risk. Scan test statistics were applied to conduct cluster
      identification in space, time and space-time. Seasonal decomposition of the time
      series was used to assess seasonal variation and trends in the data. RESULTS:
      There was geographic variability in the rates of NGI with higher notifications in
      the south compared to the north. Incidence of NGI exhibited seasonality with
      peaks in the fall months for most years. Two possible outbreaks were detected in
      the fall of 1995 and 2001, of which one coincided with a previously recognized
      outbreak. Overall, incidence of NGI fluctuated from 1991 to 2001 followed by a
      tendency for rates to decrease from 2002 to 2008. CONCLUSIONS: The distribution
      of NGI notifications varied widely according to geographic region, season and
      year. While the analyses highlighted a possible bias in the surveillance data,
      this information is beneficial for generating hypotheses about risk factors for
      infection.

PMID- 22642703
TI  - Revisiting microbial keratinases: next generation proteases for sustainable
      biotechnology.
AB  - Keratinases are special proteases which attack the highly recalcitrant keratin
      substrates. They stand apart from the conventional proteases due to their broad
      substrate specificity towards a variety of insoluble keratin rich substrates like
      feather, wool, nail, hair. Owing to this ability, keratinases find immense
      applications in various environmental and biotechnological sectors. The current
      boost in keratinase research has come up with the discovery of the ability of
      keratinases to address the challenging issue of prion decontamination. Here we
      present a comprehensive review on microbial keratinases giving an account of
      chronological progress of research along with the major milestones. Major focus
      has been on the key characteristics of keratinases, such as substrate
      specificity, keratin degradation mechanisms, molecular properties, and their role
      in prion decontamination along with other pharmaceutical applications. We
      conclude by critically evaluating the present state of the keratinases discussing
      their commercial status along with future research directions.

PMID- 22642710
TI  - Binding of intrinsic and extrinsic features in working memory.
AB  - There is ongoing debate concerning the mechanisms of feature binding in working
      memory. In particular, there is controversy regarding the extent to which these
      binding processes are automatic. The present article demonstrates that binding
      mechanisms differ depending on whether the to-be-integrated features are
      perceived as forming a coherent object. We presented a series of experiments that
      investigated the binding of color and shape, whereby color was either an
      intrinsic feature of the shape or an extrinsic feature of the shape's background.
      Results show that intrinsic color affected shape recognition, even when it was
      incidentally studied and irrelevant for the recognition task. In contrast,
      extrinsic color did not affect shape recognition, even when the association of
      color and shape was encoded and retrievable on demand. This strongly suggests
      that binding of intrinsic intra-item information but not extrinsic contextual
      information is obligatory in visual working memory. We highlight links to
      perception as well as implicit and explicit long-term memory, which suggest that
      the intrinsic-extrinsic dimension is a principle relevant to multiple domains of
      human cognition.

PMID- 22642711
TI  - Differential processing of thematic and categorical conceptual relations in
      spoken word production.
AB  - Studies of semantic context effects in spoken word production have typically
      distinguished between categorical (or taxonomic) and associative relations.
      However, associates tend to confound semantic features or morphological
      representations, such as whole-part relations and compounds (e.g., BOAT-anchor,
      BEE-hive). Using a picture-word interference paradigm and functional magnetic
      resonance imaging (fMRI), we manipulated categorical (COW-rat) and thematic (COW
      pasture) TARGET-distractor relations in a balanced design, finding interference
      and facilitation effects on naming latencies, respectively, as well as
      differential patterns of brain activation compared with an unrelated distractor
      condition. While both types of distractor relation activated the middle portion
      of the left middle temporal gyrus (MTG) consistent with retrieval of conceptual
      or lexical representations, categorical relations involved additional activation
      of posterior left MTG, consistent with retrieval of a lexical cohort. Thematic
      relations involved additional activation of the left angular gyrus. These results
      converge with recent lesion evidence implicating the left inferior parietal lobe
      in processing thematic relations and may indicate a potential role for this
      region during spoken word production.

PMID- 22642704
TI  - Serologic evidence of human influenza virus infections in swine populations,
      Cambodia.
AB  - BACKGROUND: This study was conducted from 2006 to 2010 and investigated the
      seroprevalence of influenza A viruses in Cambodian pigs, including human H1N1,
      H3N2, 2009 pandemic H1N1 (A(H1N1)pdm09), and highly pathogenic avian H5N1
      influenza A viruses. METHODS: A total of 1147 sera obtained from pigs in Cambodia
      were tested by haemagglutination inhibition (HI) assays for antibody to human
      influenza A viruses along with both HI and microneutralization (MN) tests to
      assess immunological responses to H5N1 virus. The results were compared by year,
      age, and province. RESULTS: Antibodies against a human influenza A virus were
      detected in 14.9% of samples. A(H1N1)pdm09 virus were dominant over the study
      period (23.1%), followed by those to human H1N1 (17.3%) and H3N2 subtypes (9.9%).
      No pigs were serologically positive for avian H5 influenza viruses. The
      seroprevalence of human H1N1 and H3N2 influenza viruses peaked in 2008, while
      that of A(H1N1)pdm09 reached a peak in 2010. No significant differences in
      seroprevalence to human influenza subtypes were observed in different age groups.
      CONCLUSIONS: Cambodian pigs were exposed to human strains of influenza A viruses
      either prior to or during this study. The implications of these high prevalence
      rates imply human-to-swine influenza virus transmission in Cambodia. Although
      pigs are mostly raised in small non-commercial farms, our preliminary results
      provide evidence of sustained human influenza virus circulation in pig
      populations in Cambodia.

PMID- 22642712
TI  - Steps, stages, and structure: finding compensatory order in scientific theories.
AB  - Stage theories are prominent and controversial in science. One possible reason
      for their appeal is that they provide order and predictability. Participants in
      Experiment 1 rated stage theories as more orderly and predictable (but less
      credible) than continuum theories. In Experiments 2-5, we showed that order
      threats increase the appeal of stage theories of grief (Experiment 2) and moral
      development (Experiments 4 and 5). Experiment 3 yielded similar results for a
      stage theory on Alzheimer's disease characterized by predictable decline,
      suggesting that preference for stage theories is independent of valence.
      Experiment 4 showed that the effect of threat on theory preference was mediated
      by the motivated perception of order, and Experiment 5 revealed that it is
      particularly the fixed order of stages that increases their appeal.

PMID- 22642713
TI  - Statistical challenges in the development and evaluation of marker-based clinical
      tests.
AB  - Exciting new technologies for assessing markers in human specimens are now
      available to evaluate unprecedented types and numbers of variations in DNA, RNA,
      proteins, or biological structures such as chromosomes. These markers, whether
      viewed individually, or collectively as a 'signature', have the potential to be
      useful for disease risk assessment, screening, early detection, prognosis,
      therapy selection, and monitoring for therapy effectiveness or disease
      recurrence. Successful translation from basic research findings to clinically
      useful test requires basic, translational, and regulatory sciences and a
      collaborative effort among individuals with varied types of expertise including
      laboratory scientists, technology developers, clinicians, statisticians, and
      bioinformaticians. The focus of this commentary is the many statistical
      challenges in translational marker research, specifically in the development and
      validation of marker-based tests that have clinical utility for therapeutic
      decision-making.

PMID- 22642715
TI  - Iminoboronates: a new strategy for reversible protein modification.
AB  - Protein modification has entered the limelight of chemical and biological
      sciences, since, by appending small molecules into proteins surfaces, fundamental
      biological and biophysical processes may be studied and even modulated in a
      physiological context. Herein we present a new strategy to modify the lysine's
      epsilon-amino group and the protein's N-terminal, based on the formation of
      stable iminoboronates in aqueous media. This functionality enables the stable and
      complete modification of these amine groups, which can be reversible upon the
      addition of fructose, dopamine, or glutathione. A detailed DFT study is also
      presented to rationalize the observed stability toward hydrolysis of the
      iminoboronate constructs.

PMID- 22642714
TI  - Increasing blood pressure and its associated factors in Canadian children and
      adolescents from the Canadian Health Measures Survey.
AB  - BACKGROUND: Canada is facing a childhood obesity epidemic. Elevated blood
      pressure (BP) is a major complication of obesity. Reports on the impact of excess
      adiposity on BP in children and adolescents have varied significantly across
      studies. We evaluated the independent effects of obesity, physical activity,
      family history of hypertension, and socioeconomic status on BP in a nationally
      representative sample of children and adolescents. METHODS: We analysed cross
      sectional data for 1850 children aged 6 to 17 years who participated in the
      Canadian Health Measures Survey, Cycle 1, 2007-2009. Systolic BP (SBP) and
      diastolic BP (DBP) were age-, sex-, and height-adjusted to z-scores (SBPZ and
      DBPZ). Body mass index (BMI) z-scores were calculated based on World Health
      Organization growth standards. Multivariate linear regression was used to
      evaluate the independent effects of relevant variables on SBPZ and DBPZ. RESULTS:
      For most age/sex groups, obesity was positively associated with SBP. Being obese
      was associated with higher DBP in adolescent boys only. The BP effect of obesity
      showed earlier in young girls than boys. Obese adolescents were estimated to have
      an average 7.6 mmHg higher SBP than normal weight adolescents. BMI had the
      strongest effect on BP among obese children and adolescents. Moderately active
      adolescent boys had higher SBP (3.9 mmHg) and DBP (4.9 mmHg) than physically
      active boys. Family history of hypertension showed effects on SBP and DBP in
      younger girls and adolescent boys. Both family income and parent education
      demonstrated independent associations with BP in young children. CONCLUSIONS: Our
      findings demonstrate the early impact of excess adiposity, insufficient physical
      activity, family history of hypertension, and socioeconomic inequalities on BP.
      Early interventions to reduce childhood obesity can, among other things, reduce
      exposure to prolonged BP elevation and the future risk of cardiovascular disease.

PMID- 22642716
TI  - Interpersonal conflict and health perceptions in long-distance caregiving
      relationships.
AB  - With job markets expanding globally and life expectancy continually increasing,
      more demands are being placed on distant relatives to provide care for their
      aging family members, creating a health care situation known as long-distance
      caregiving. An online survey explored the relations between negative health
      perceptions by long-distance caregivers and conflict frequency and conflict
      strategy usage. The authors observed positive significant relations between
      distant caregiver negative health perceptions and conflict frequency and usage of
      the distributive and avoidance conflict strategies. However, they observed no
      significant associations between distant caregiver negative health perceptions
      and usage of the two integrative strategies. Implications for long-distance
      caregiving communication are discussed.

PMID- 22642717
TI  - van der Waals epitaxy of MoS2 layers using graphene as growth templates.
AB  - We present a method for synthesizing MoS(2)/Graphene hybrid heterostructures with
      a growth template of graphene-covered Cu foil. Compared to other recent reports,
      (1, 2)  a much lower growth temperature of 400  degrees C is required for this
      procedure. The chemical vapor deposition of MoS(2) on the graphene surface gives
      rise to single crystalline hexagonal flakes with a typical lateral size ranging
      from several hundred nanometers to several micrometers. The precursor (ammonium
      thiomolybdate) together with solvent was transported to graphene surface by a
      carrier gas at room temperature, which was then followed by post annealing. At an
      elevated temperature, the precursor self-assembles to form MoS(2) flakes
      epitaxially on the graphene surface via thermal decomposition. With higher amount
      of precursor delivered onto the graphene surface, a continuous MoS(2) film on
      graphene can be obtained. This simple chemical vapor deposition method provides a
      unique approach for the synthesis of graphene heterostructures and surface
      functionalization of graphene. The synthesized two-dimensional MoS(2)/Graphene
      hybrids possess great potential toward the development of new optical and
      electronic devices as well as a wide variety of newly synthesizable compounds for
      catalysts.

PMID- 22642718
TI  - Microwave-enhanced solid-phase synthesis of N,N'-linked aliphatic oligoureas and
      related hybrids.
AB  - A practical and efficient microwave-assisted solid-phase method for the synthesis
      of N,N'-linked oligoureas and related amide/urea hybrid oligomers, featuring the
      use of succinimidyl (2-azido-2-substituted ethyl) carbamate monomers, is
      reported. The rate enhancement of urea formation under microwave irradiation
      combined with the mild conditions of the phosphine-based azide reduction makes
      this approach very effective for routine synthesis of oligoureas and possibly for
      library production.

PMID- 22642719
TI  - Retention and transport of silica nanoparticles in saturated porous media: effect
      of concentration and particle size.
AB  - Investigations on factors that affect the fate and transport of nanoparticles
      (NPs) remain incomplete to date. In the present study, we conducted column
      experiments using 8 and 52 nm silica NPs to examine the effects of NPs'
      concentration and size on their retention and transport in saturated porous
      media. Results showed that higher particle number concentration led to lower
      relative retention and greater surface coverage. Smaller NPs resulted in higher
      relative retention and lower surface coverage. Meanwhile, evaluation of size
      effect based on mass concentration (mg/L) vs particle number concentration
      (particles/mL) led to different conclusions. A set of equations for surface
      coverage calculation was developed and applied to explain the different results
      related to the size effects when a given mass concentration (mg/L) and a given
      particle number concentration were used. In addition, we found that the retained
      8 nm NPs were released upon lowered solution ionic strength, contrary to the
      prediction by the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. The study
      herein highlights the importance of NPs' concentration and size on their behavior
      in porous media. To the best of our knowledge, it is the first report of an
      improved equation for surface coverage calculation using column breakthrough
      data.

PMID- 22642720
TI  - General colorimetric detection of proteins and small molecules based on cyclic
      enzymatic signal amplification and hairpin aptamer probe.
AB  - In this work, we developed a simple and general method for highly sensitive
      detection of proteins and small molecules based on cyclic enzymatic signal
      amplification (CESA) and hairpin aptamer probe. Our detection system consists of
      a hairpin aptamer probe, a linker DNA, two sets of DNA-modified AuNPs, and
      nicking endonuclease (NEase). In the absence of a target, the hairpin aptamer
      probe and linker DNA can stably coexist in solution. Then, the linker DNA can
      assemble two sets of DNA-modified AuNPs, inducing the aggregation of AuNPs.
      However, in the presence of a target, the hairpin structure of aptamer probe is
      opened upon interaction with the target to form an aptamer probe-target complex.
      Then, the probe-target complex can hybridize to the linker DNA. Upon formation of
      the duplex, the NEase recognizes specific nucleotide sequence and cleaves the
      linker DNA into two fragments. After nicking, the released probe-target complex
      can hybridize with another intact linker DNA and the cycle starts anew. The
      cleaved fragments of linker DNA are not able to assemble two sets of DNA-modified
      AuNPs, thus a red color of separated AuNPs can be observed. Taking advantage of
      the AuNPs-based sensing technique, we are able to assay the target simply by UV
      vis spectroscopy and even by the naked eye. Herein, we can detect the human
      thrombin with a detection limit of 50 pM and adenosine triphosphate (ATP) with a
      detection limit of 100 nM by the naked eye. This sensitivity is about 3 orders of
      magnitude higher than that of traditional AuNPs-based methods without
      amplification. In addition, this method is general since there is no requirement
      of the NEase recognition site in the aptamer sequence. Furthermore, we proved
      that the proposed method is capable of detecting the target in complicated
      biological samples.

PMID- 22642721
TI  - The pharmacokinetics of darexaban are not affected to a clinically relevant
      degree by rifampicin, a strong inducer of P-glycoprotein and CYP3A4.
AB  - AIMS: We investigated the effects of rifampicin on the pharmacokinetics (PK) of
      the direct clotting factor Xa inhibitor darexaban (YM150) and its main active
      metabolite, darexaban glucuronide (YM-222714), which almost entirely determines
      the antithrombotic effect. METHODS: In this open-label, single-sequence study, 26
      healthy men received one dose of darexaban 60 mg on day 1 and oral rifampicin 600
      mg once daily on days 4-14. On day 11, a second dose of darexaban 60 mg was given
      with rifampicin. Blood and urine were collected after study drug administration
      on days 1-14. The maximal plasma drug concentration (C(max)) and exposure [area
      under the plasma concentration-time curve from time zero to time of quantifiable
      measurable concentration; (AUC(last)) or AUC(last) extrapolated to infinity
      (AUC(infinity))] were assessed by analysis of variance of PK. Limits for
      statistical significance of 90% confidence intervals for AUC and C(max) ratios
      were predefined as 80-125%. RESULTS: Darexaban glucuronide plasma exposure was
      not affected by rifampicin; the geometric mean ratio (90% confidence interval) of
      AUC(last) with/without rifampicin was 1.08 (1.00, 1.16). The C(max) of darexaban
      glucuronide increased by 54% after rifampicin [ratio 1.54 (1.37, 1.73)]. The
      plasma concentrations of darexaban were very low (<1% of darexaban glucuronide
      concentrations) with and without rifampicin. Darexaban alone or in combination
      with rifampicin was generally safe and well tolerated. CONCLUSIONS: Overall,
      rifampicin did not affect the PK profiles of darexaban glucuronide and darexaban
      to a clinically relevant degree, suggesting that the potential for drug-drug
      interactions between darexaban and CYP3A4 or P-glycoprotein-inducing agents is
      low.

PMID- 22642722
TI  - Probing the soybean Bowman-Birk inhibitor using recombinant antibody fragments.
AB  - The nutritional and health benefits of soy protein have been extensively studied
      over recent decades. The Bowman-Birk inhibitor (BBI), derived from soybeans, is a
      double-headed inhibitor of chymotrypsin and trypsin with anticarcinogenic and
      anti-inflammatory properties, which have been demonstrated in vitro and in vivo.
      However, the lack of analytical and purification methodologies complicates its
      potential for further functional and clinical investigations. This paper reports
      the construction of anti-BBI antibody fragments based on the principle of protein
      design. Recombinant antibody (scFv and diabody) molecules targeting soybean BBI
      were produced and characterized in vitro (K(D)~1.10(-9) M), and the antibody
      binding site (epitope) was identified as part of the trypsin-specific reactive
      loop. Finally, an extremely fast purification strategy for BBI from soybean
      extracts, based on superparamagnetic particles coated with antibody fragments,
      was developed. To the best of the authors' knowledge, this is the first report on
      the design and characterization of recombinant anti-BBI antibodies and their
      potential application in soybean processing.

PMID- 22642723
TI  - Psychometric evaluation of a new instrument to measure disease self-management of
      the early stage chronic kidney disease patients.
AB  - AIMS AND OBJECTIVES: This study aims to develop a valid and reliable chronic
      kidney disease self-management instrument (CKD-SM) for assessing early stage
      chronic kidney disease patients' self-management behaviours. BACKGROUND:
      Enhancing early stage chronic kidney disease patients' self-management plays a
      key role in delaying the progression of chronic kidney disease. Healthcare
      provider understanding of early stage chronic kidney disease patients' self
      management behaviours can help develop effective interventions. A valid and
      reliable instrument for measuring chronic kidney disease patients' self
      management behaviours is needed. DESIGN: A cross-sectional descriptive study
      collected data for principal components analysis with oblique rotation. METHODS:
      Mandarin- or Taiwanese-speaking adults with chronic kidney disease (n=252) from
      two medical centres and one regional hospital in Southern Taiwan completed the
      CKD-SM. Construct validity was evaluated by exploratory factor analysis. Internal
      consistency and test-retest reliability were estimated by Cronbach's alpha and
      Pearson correlation coefficients. RESULTS: Four factors were extracted and
      labelled self-integration, problem-solving, seeking social support and adherence
      to recommended regimen. The four factors accounted for 60.51% of the total
      variance. Each factor showed acceptable internal reliability with Cronbach's
      alpha from 0.77-0.92. The test-retest correlations for the CKD-SM was 0.72.
      CONCLUSION: The psychometric quality of the CKD-SM instrument was satisfactory.
      Research to conduct a confirmatory factor analysis to further validate this new
      instrument's construct validity is recommended. RELEVANCE TO CLINICAL PRACTICE:
      The CKD-SM instrument is useful for clinicians who wish to identify the problems
      with self-management among chronic kidney disease patients early. Self-management
      assessment will be helpful to develop intervention tailored to the needs of the
      chronic kidney disease population.

PMID- 22642724
TI  - An assessment of the diagnostic criteria for sessile serrated adenoma/polyps:
      SSA/Ps using image processing software analysis for Ki67 immunohistochemistry.
AB  - BACKGROUND: Serrated polyps belong to a heterogeneous group of lesions that are
      generally characterized morphologically. This type of lesion is thought to be the
      precursor of sporadic carcinomas with microsatellite instability, and probably
      also the precursor for CpG island-methylated microsatellite-stable carcinomas.
      For practical purposes, according to the 2010 WHO classification, the diagnostic
      criteria for sessile serrated adenomas/polyps (SSA/Ps) was established by the
      research project "Potential of Cancerization of Colorectal Serrated Lesions" led
      by the Japanese Society for Cancer of the Colon and Rectum. The aim of this study
      was to evaluate the validity of the morphologic characteristics established in
      Japan by using immunohistochemical staining for Ki-67. METHODS: To calculate the
      target cells, 2 contiguous crypts which could be detected from the bottom of the
      crypt to the surface of the colorectal epithelium were selected. To validate the
      proliferative activity, we evaluated the percentage and the asymmetrical staining
      pattern of Ki67 positive cells in each individual crypt. To examine the
      immunoreactivity of Ki67, computer-assisted cytometrical analysis was performed.
      RESULTS: SSA/Ps had a higher proliferative activity as compared to hyperplastic
      polyps (HPs) based on the difference in incidence of Ki67 positive cells, and the
      former also exhibited a significantly higher asymmetric distribution of these
      cells as compared to HPs, even in lesions with a diameter <10 mm. CONCLUSION: We
      conclude that assessment of the pathological findings of SSA/Ps, including crypt
      dilation, irregularly branching crypts, and horizontally arranged basal crypts
      (inverted T- and/or L-shaped crypts) is appropriate to show a significantly
      higher proliferative activity as compared to HPs. Further, the use of two
      dimensional image analysis software is an objective and reproducible method for
      this type of histological examination. VIRTUAL SLIDES: The virtual slides for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/6718091416698112.

PMID- 22642725
TI  - Why invest in early psychosis intervention services?

PMID- 22642726
TI  - First-episode psychoses. Recommended roles for the psychiatrist: World
      Psychiatric Association Committee on Education.

PMID- 22642727
TI  - From bench to bedside: translating new research from genetics and neuroimaging
      into treatment development for early-onset schizophrenia.
AB  - OBJECTIVE: Children and adolescents with schizophrenia share a similar pattern of
      phenomenological, genetic and cognitive abnormalities to adults with
      schizophrenia. However, an early-onset of schizophrenia (EOS) (prior to 18 years
      of age) is associated with a higher frequency of risk indicators associated with
      schizophrenia (e.g. developmental delays and familial spectrum disorders) and a
      worse long-term outcome. This overview examines recent research on the
      neurobiological alterations, possible causes, developmental trajectory and
      treatment of EOS and attempts to identify gaps in the field. METHOD: The authors
      provide a selective review of major findings from genetics, neuroimaging and
      treatment studies of pediatric schizophrenia that were presented at a workshop
      sponsored by the National Institute of Mental Health. These data are synthesized
      in conjunction with preclinical studies into a model of the pathophysiology of
      EOS. RESULTS: EOS is associated with a high frequency of cytogenetic
      abnormalities (e.g. velocardiofacial syndrome, sex chromosome anomalies) and
      other rare denovo chromosomal aberrations. Brain imaging research in adolescents
      with EOS has revealed a progressive loss of cortical grey matter post-onset of
      psychosis and subtle abnormalities in white matter microstructure. Although EOS
      patients are more likely to be treatment-refractory than their adult
      counterparts, there are substantial data that this subgroup is particularly
      responsive to clozapine. CONCLUSIONS: Genetic or environmental factors operating
      during adolescence that reduce frontal capacity might contribute to an EOS in
      susceptible individuals. Additional longitudinal studies of adolescents with
      schizophrenia are needed to better understand the relationship between structural
      changes in fronto-limbic regions, stress responsivity, and cognitive and
      neurochemical development.

PMID- 22642728
TI  - Review of the operational definition for first-episode psychosis.
AB  - AIM: Given the growing interest in the study of first-episode psychosis, clinical
      and research programmes would benefit from a conceptual clarification of how to
      operationalize 'first-episode psychosis'. We review the variety of definitions in
      use and discuss their relative merits with respect to both clinical (e.g. early
      treatment) and research (e.g. obtaining meaningfully homogeneous populations)
      agendas. METHODS: We completed a selective review of the literature to
      investigate how first-episode psychosis was operationally defined. RESULTS:
      Operational definitions for 'first-episode psychosis' fall largely into three
      categories: (i) first treatment contact; (ii) duration of antipsychotic
      medication use; and (iii) duration of psychosis. Each definitional category
      contains a number of underlying assumptions that contribute to the strengths and
      weaknesses of the definition. CONCLUSIONS: The term 'first-episode psychosis' as
      used within clinical and research settings is misleading regardless of which
      operational definition is used. This term is typically used to refer to
      individuals early in the course of a psychotic illness or treatment rather than
      individuals who are truly in the midst of a first 'episode' of illness. The
      alternative of 'recent-onset psychosis' with related definitions based on
      'duration of psychosis' is proposed. Based on this review, we provide suggestions
      with regard to the overarching pragmatic consideration of setting up a clinical
      service that can attract and assemble a population of early psychosis patients
      for the related purposes of treatment and research.

PMID- 22642729
TI  - Economic impact of services for first-episode psychosis: a decision model
      approach.
AB  - AIM: To assess the impact of early intervention (EI) services on service costs
      for people with first-episode psychosis. METHODS: A decision model was
      constructed to map the care pathways following input from EI services and from
      standard care. A Markov process was used to run the model over 18 2-month cycles.
      Probabilities and costs for the model of admissions, readmissions and use of
      community services were obtained from the literature, routine sources and expert
      opinion. One-way and probabilistic sensitivity analyses were conducted to address
      uncertainty around the parameter estimates. RESULTS: The model estimated 1 year
      costs to be L9422 for EI and L14,394 for standard care. The respective figures
      over 3 years were L26,568 and L40,816. One-way sensitivity analyses revealed that
      the results were robust to changes in most parameters with the exception of the
      readmission rate. A relatively small decrease in the readmission rate for
      standard care patients would eliminate the cost saving. The probabilistic
      sensitivity analyses also showed that the results were robust to parameter
      changes. CONCLUSIONS: This study suggests cost savings associated with EI.
      However, caution is required as the model is relatively simple and relies on a
      number of assumptions.

PMID- 22642730
TI  - A comparison of early psychosis treatment services using consensus and evidence
      based performance measures: moving towards setting standards.
AB  - OBJECTIVE: This study used data from two Canadian early psychosis programs to
      assess the feasibility of using common performance measures and to assess the
      extent to which each program meets suggested standards for early intervention.
      METHODS: Data were extracted from administrative databases and supplemented by
      health records for 332 individuals admitted to two services in order to calculate
      values for 19 performance indicators for January 2000 to January 2004. Inter
      rater reliability was established for data abstraction. RESULTS: The two samples
      had similar demographic and clinical profiles. There were no statistically
      significant differences in 1-, 2- and 3-year admission rates (year 1: 27% vs.
      30%, P=0.625; year 2: 31% vs. 38%, P=0.248; year 3: 35% vs. 42%, P=0.260),
      duration of untreated psychosis (DUP) (24 vs. 28 weeks; P=0.844) and positive
      symptom remission at 1 year (72% vs. 78%; P=0.285). There were statistically
      significant differences between the two services in mean wait time (18 vs. 13
      days; P=0.045), proportion of patients on second-generation anti-psychotics at 1
      year (75% vs. 89%; P=0.002), and proportion of patients adherent to antipsychotic
      medication for a minimum of 12 months (76% vs. 83%; P=0.007). CONCLUSION: The
      data provides useful information on the feasibility of implementing key
      performance measures across early psychosis programs to assess the extent to
      which they are meeting standards for such services.

PMID- 22642731
TI  - Can targeted early intervention improve functional recovery in psychosis? A
      historical control evaluation of the effectiveness of different models of early
      intervention service provision in Norfolk 1998-2007.
AB  - AIMS: This paper assesses the impact of different models of early intervention
      (EI) service provision on functional recovery and inpatient hospital admission.
      The study compares the outcome of a comprehensive EI team with a partial model
      (community mental health team (CMHT) plus specialist support) and traditional
      care (generic CMHT) over a 10-year period. METHODS: The design is in comparison
      with historical control. The study compares the functional recovery outcomes of
      three cohorts from the same geographical area over the period 1998-2007. The
      primary outcomes were partial and full functional recovery defined with respect
      to readily identifiable UK benefit system thresholds and psychiatric inpatient
      admission days at 1 and 2 years post-referral. RESULTS: Only 15% of individuals
      made a full or partial functional recovery at 2 years under the care of a
      traditional generic CMHT in 1998. In 2007, 52% of the cases were making a full or
      partial functional recovery under the care of the comprehensive EI team. A large
      reduction in inpatient admissions was associated with the EI strategy.
      CONCLUSIONS: The implementation of comprehensive EI teams can have a major impact
      in improving functional recovery outcomes in psychosis and reducing inpatient
      admissions. Partial implementation using limited funding of specialist workers in
      collaboration with traditional care appeared to have a more limited effect on
      these recovery dimensions. The implementation of targeted EI in psychosis
      strategies can result in substantive functional benefits.

PMID- 22642732
TI  - Improving detection of first-episode psychosis by mental health-care services
      using a self-report questionnaire.
AB  - OBJECTIVE: To examine the utility of the Community Assessment of Psychic
      Experiences (CAPE)-42, a self-report questionnaire, to improve detection of first
      episode psychosis in new referrals to mental health services. METHOD: At first
      contact with mental health-care services patients were asked to complete the CAPE
      42 and were then routinely diagnosed by a clinician. Standard diagnoses were
      obtained by means of the mini-Schedule for Clinical Assessment in
      Neuropsychiatry. RESULTS: Of the 246 included patients, 26 (10.6%) were diagnosed
      with psychosis according to the mini-Schedule for Clinical Assessment in
      Neuropsychiatry. Only 10 of them were recognized by clinical routine, and 16
      psychotic patients were not properly identified. Using an optimal cut-off of 50
      on the frequency or distress dimension of the positive subscale of the CAPE-42
      detected 14 of these misdiagnosed patients. The sensitivity of the CAPE-42 at
      this cut-off point was 77.5 and the specificity 70.5. CONCLUSION: Systematic
      screening of patients using a self-report questionnaire for psychotic symptoms
      improves routine detection of psychotic patients when they first come into
      contact with mental health services.

PMID- 22642733
TI  - 'Schizophrenia postdrome': a study of low-level psychotic experience after
      remission of first-episode schizophrenia.
AB  - BACKGROUND: Despite remission being the primary objective following the first
      episode of schizophrenia, clinically stabilized patients nevertheless relapse.
      AIM: To assess the extent and fluctuation of low-level psychotic symptoms in
      patients who are in remission after first-episode schizophrenia and consider
      whether this is equivalent to symptomatology experienced by those at 'ultra high
      risk' (UHR) of developing first-episode psychosis. METHODS: We examined the
      phenomenological characteristics of 11 patients who fulfilled international
      remission criteria using the Structured Interview for Prodromal Symptoms and
      compared this cohort with an UHR sample. RESULTS: Remitted patients were
      experiencing attenuated positive symptoms (73%) and brief limited intermittent
      psychotic symptoms (18%), features that were similarly prevalent in the UHR
      group. There was no significant fluctuation in these low-level symptoms over the
      course of four interviews. CONCLUSIONS: Although further research is required in
      this novel field, such features could form the building blocks for better
      prediction of psychotic relapse.

PMID- 22642734
TI  - Predictors of therapeutic alliance in early psychosis.
AB  - AIM: To increase our understanding of the therapeutic alliance formation in
      clients with early psychosis by examining the predictive value of three major
      factors: symptoms; insight; and global functioning. METHODS: One hundred fifty
      individuals with early psychosis were recruited from various clinical settings.
      The measures used were the Working Alliance Inventory, the Brief Psychiatric
      Rating Scale, the Insight Scale and the Client Assessment of Strengths Interests
      and Goals. RESULTS: Multiple linear regressions were performed and revealed a
      model including insight, friends, leisure, medication side effects and quality of
      life explaining 22% of the variance. CONCLUSION: The variables included in the
      model are coherent with the literature on alliance. However, other variables
      contributing to the establishment of the therapeutic alliance remain to be
      identified in future research on treatment of early psychosis.

PMID- 22642735
TI  - Specialized home treatment versus hospital-based outpatient treatment for first
      episode psychosis: a randomized clinical trial.
AB  - OBJECTIVE: This pilot study compared the effectiveness of specialized care that
      was home based versus hospital based for individuals experiencing their first
      psychotic episode. METHOD: A randomized controlled trial design was used. A total
      of 29 subjects were interviewed at baseline, 3 and 9 months. Repeated measures
      analysis of variance was employed to test for statistically significant changes
      over time within and between groups with regard to community psychosocial
      functioning and symptom severity. RESULTS: Our findings indicate that subjects in
      both the home-based and hospital-based programmes significantly improved with
      regard to symptoms and community functioning over time. However, the rates of
      change over time were not significantly different between the two programmes.
      There was a statistically significant difference between programmes with regard
      to the proportion of subjects with less than two visits (i.e. either did not
      attend their first assessment or attended follow-up visits after their
      assessment). CONCLUSIONS: This was a modest pilot study and the sample was too
      small to allow definitive conclusions to be drawn. However, the results raise
      questions about differences in initial treatment engagement. They suggest the
      need for additional research focusing on interventions that promote initial
      treatment seeking.

PMID- 22642736
TI  - Who should swing the stethoscope? An audit of baseline physical examination and
      blood monitoring on new patients accepted by an early intervention in psychosis
      team.
AB  - AIM: It has been established that patients with severe mental illness are at
      increased risk of physical illness and that physical health screening should be
      performed when an individual experiences a first episode of psychosis. The aim of
      the audit was to examine how physical health screening was achieved in the real
      world of an early intervention in psychosis (EIP) service in Scotland. Of
      particular interest was considering if primary or secondary care were more
      effective in providing specific physical health assessment for those presenting
      to the service. METHODS: A case note audit was performed. RESULTS: The audit
      shows that physical examination and blood tests were being completed in the
      majority of service users under the care of the Esteem service. However, an
      unacceptably high number were not undergoing sufficient initial screening for
      metabolic syndrome or having baseline monitoring prior to commencing
      antipsychotic medication. CONCLUSIONS: Our results suggest that relying on
      primary care to provide physical health screening was not an effective approach
      in a population experiencing first-episode psychosis. Having a psychiatrist
      motivated to perform physical health screening within the EIP team may help to
      improve the uptake of physical health screening. Strategies to improve physical
      health screening in EIP services are discussed.

PMID- 22642738
TI  - Severe liver dysfunction possibly caused by the combination of interferon beta-1b
      therapy and melilot (sweet clover) supplement.
AB  - WHAT IS KNOWN AND OBJECTIVE: We report a case of severe liver dysfunction
      exacerbated after interferon beta (IFNB)-1b injection in a patient with multiple
      sclerosis (MS) who had been taking a melilot (sweet clover) supplement. Although
      IFNB-1b therapy for MS can cause mild liver dysfunction, severe hepatotoxicity
      attributable to supplement use has been reported. CASE SUMMARY: A 23-year-old
      Japanese woman taking a melilot supplement containing coumarin at 10 mg/day for 3
      years was admitted to our hospital to receive IFNB-1b therapy for MS. Fourteen
      days after subcutaneous injection of IFNB-1b every other day, her aspartate
      transaminase (AST) and alanine aminotransferase (ALT) levels were elevated at 235
      and 681 IU/L, respectively. After the discontinuation of IFNB-1b therapy and
      supplement intake, AST and ALT returned to normal levels. Later, she started
      receiving an intramuscular injection of IFNB-1a weekly without supplement intake.
      She was able to continue IFNB-1a therapy this time, showing a slight elevation of
      AST level at 61 IU/L. WHAT IS NEW AND CONCLUSION: The combination of IFNB-1b
      therapy and melilot supplement intake may cause severe liver dysfunction in
      patients with MS. Given the doubtful value of the supplement, we suggest that it
      should be avoided by patients receiving interferon therapy.

PMID- 22642739
TI  - Use of online health information resources by American Indians and Alaska
      Natives.
AB  - According to the Office of Minority Health, an estimated 4.9 million people
      living in the United States consider themselves American Indian or Alaska Native,
      either alone or in combination with one or more races/ethnicities. American
      Indians or Alaska Natives comprise a racial/ethnic group experiencing serious
      health disparities, with little if any improvement in health outcomes over the
      past several decades. This study was designed to explore use of the Internet as a
      health information source among American Indians in the Central Plains region of
      the United States. The authors recruited 998 Natives in the region from May 2008
      to December 2009 at powwows, health fairs, focus groups, career fairs and
      conferences, and other social and cultural events, and asked them to complete a
      self-administered survey. Although compared with data from the general
      population, American Indians or Alaska Natives in this sample may seem to be more
      frequent Internet users, their use of modern wireless devices is limited, and
      their use of the Internet to access health information is lower in comparison
      with the adult U.S. population. Natives living in the Central Plains region face
      generational differences in general and health-related use of the Internet.
      Inadequate availability of culturally appropriate health information websites may
      drive American Indians or Alaska Natives toward search engines and general
      information websites.

PMID- 22642740
TI  - Can losartan and blood pressure control peri arteriovenous fistula creation
      ameliorate the early associated left ventricular hypertrophic response a
      randomised placebo controlled trial.
AB  - BACKGROUND: Haemodialysis results in a left ventricular hypertrophic response. It
      is unclear whether tight blood pressure control or particular medications might
      attenuate this response. We sought to determine, in a pre-dialysis cohort on
      atenolol, whether Losartan might attenuate left ventricular hypertrophy post
      arteriovenous fistula creation in end stage kidney disease. MATERIALS AND
      METHODS: Placebo controlled double blind randomisation of 26 patients to fixed
      dose atenolol plus fixed dose losartan or placebo occurred 1 day prior to fistula
      creation. Pre-randomisation echocardiography was repeated at 1 week and 1-month.
      Measurement was undertaken of blood pressure, heart rate, brain natriuretic
      peptide, serum creatinine and estimated glomerular filtration rate. The primary
      pre-specified endpoint was the change in left ventricular mass at 1 month. Non
      parametric statistical comparison was performed within and between groups.
      RESULTS: There was no difference in left ventricular mass between our groups 1
      month post fistula creation. In the entire cohort, change in left ventricular
      mass was driven by changes in blood pressure and volume loading. Blood pressure
      changes correlated with left ventricular mass changes seen shortly post
      arteriovenous fistula creation, suggesting blood pressure control during this
      time period may be an important part of the management of end stage kidney
      disease. CONCLUSIONS: We did not see an advantage with the use of losartan with
      respect to diminution of the LVM response. However, our demonstrated change in
      LVM was relatively small compared to previous literature and suggests a possible
      role for beta blockade as a neurohormonal modulator around the time of
      arteriovenous fistula creation. TRIAL REGISTRATION: Clinical trials.gov
      (NCT00602004).

PMID- 22642741
TI  - Controlling the abruptness of axial heterojunctions in III-V nanowires: beyond
      the reservoir effect.
AB  - Heterostructure nanowires have many potential applications due to the avoidance
      of interface defects by lateral strain relaxation. However, most heterostructure
      semiconductor nanowires suffer from persistent interface compositional grading,
      normally attributed to the dissolution of growth species in the common alloy seed
      particles. Although progress has been made for some material systems, most binary
      material combinations remain problematic due to the interaction of growth species
      in the alloy. In this work we investigate the formation of interfaces in InAs
      GaAs heterostructures experimentally and theoretically and demonstrate a
      technique to attain substantially sharper interfaces. We show that by pulsing the
      Ga source during heterojunction formation, In is pushed out before GaAs growth
      initiates, greatly reducing In carry-over. This procedure will be directly
      applicable to any nanowire system with finite nonideal solubility of growth
      species in the alloy seed particle and greatly improve the applicability of these
      structures in future devices.

PMID- 22642742
TI  - Fenugreek with reduced bitterness prevents diet-induced metabolic disorders in
      rats.
AB  - BACKGROUND: Various therapeutic effects of fenugreek (Trigonella foenum-graecum
      L.) on metabolic disorders have been reported. However, the bitterness of
      fenugreek makes it hard for humans to eat sufficient doses of it for achieving
      therapeutic effects. Fenugreek contains bitter saponins such as protodioscin.
      Fenugreek with reduced bitterness (FRB) is prepared by treating fenugreek with
      beta-glucosidase. This study has been undertaken to evaluate the effects of FRB
      on metabolic disorders in rats. METHODS: Forty Sprague-Dawley rats were fed with
      high-fat high-sucrose (HFS) diet for 12 week to induce mild glucose and lipid
      disorders. Afterwards, the rats were divided into 5 groups. In the experiment 1,
      each group (n = 8) was fed with HFS, or HFS containing 2.4% fenugreek, or HFS
      containing 1.2%, 2.4% and 4.8% FRB, respectively, for 12 week. In the experiment
      2, we examined the effects of lower doses of FRB (0.12%, 0.24% and 1.2%) under
      the same protocol (n = 7 in each groups). RESULTS: In the experiment 1, FRB dose
      dependently reduced food intake, body weight gain, epididymal white adipose
      tissue (EWAT) and soleus muscle weight. FRB also lowered plasma and hepatic lipid
      levels and increased fecal lipid levels, both dose-dependently. The Plasma total
      cholesterol levels (mmol/L) in the three FRB and Ctrl groups were 1.58 +/- 0.09,
      1.45 +/- 0.05*, 1.29 +/- 0.07* and 2.00 +/- 0.18, respectively (*; P < 0.05 vs.
      Ctrl). The Hepatic total cholesterol levels (mmol/g liver) were 0.116 +/- 0.011,
      0.112 +/- 0.006, 0.099 +/- 0.007* and 0.144 +/- 0.012, respectively (*; P < 0.05
      vs. Ctrl). The calculated homeostasis model assessment as an index of insulin
      resistance (HOMA-IR) indicated 0.52 +/- 0.04*, 0.47 +/- 0.06*, 0.45 +/- 0.05* and
      1.10 +/- 0.16, respectively (*; P < 0.05 vs. Ctrl). None of the FRB groups showed
      any adverse effect on the liver, kidney or hematological functions. In the
      experiment 2, no significant difference of food intake was observed, while the
      1.2% FRB group alone showed nearly the same effects on glucose and lipid
      metabolism as in the experiment 1. CONCLUSIONS: Thus we have demonstrated that
      FRB (1.2 ~ 4.8%) prevents diet-induced metabolic disorders such as insulin
      resistance, dyslipidemia and fatty liver.

PMID- 22642743
TI  - Young people with depression and their satisfaction with the quality of care they
      receive from a primary care youth mental health service: a qualitative study.
AB  - AIM: To examine how satisfied young people with depression are with the quality
      of care they receive from clinicians of a primary care service for young people
      with mental health problems. BACKGROUND: There is a high prevalence of youth
      depression, but few studies have been undertaken to examine whether young people
      are satisfied with the care they receive in primary care youth mental health
      services. DESIGN: Qualitative interpretative phenomenological analysis. METHOD:
      Individual, semi-structured, in-depth, audio-recorded interviews were carried out
      between March and September 2009. A purposive sample of 26 young people with
      depression, average age 18 years, were recruited through clinicians of a primary
      care service for young people with mental health problems, in Melbourne. RESULTS:
      Three overlapping themes highlight youth participants' satisfaction with care:
      First, clinicians being youth-friendly, highlights how, overall, clinicians are
      perceived as approachable and supportive, understanding and non-judgemental.
      Second, clinicians adopting a broad-based style of care illustrates that their
      use primarily of psychosocial therapies, and the judicious use of antidepressant
      medication, is received favourably by youth. Third, care facilitating recovery
      highlights that clinicians' youth-friendly and broad-based approach enables a
      therapeutic dialogue to be established with the young people, contributing to
      recovery from depression; recovery, in turn, enhances satisfaction with
      clinicians. CONCLUSION: Youth-friendliness is an important expectation of mental
      health nurses and other clinicians within the youth service. This engagement
      style provides a useful framework for clinicians to adopt a broad-based approach
      to care. Ultimately, care should facilitate recovery from depression, and this
      strengthens satisfaction with mental health nurses and other clinicians.
      RELEVANCE TO CLINICAL PRACTICE: The findings make an important contribution to
      knowledge and research in mental health nursing. In particular, youth
      friendliness is an important prerequisite for continuing engagement with
      services, and a broad-based approach to care should be adopted.

PMID- 22642748
TI  - Erratum.

PMID- 22642744
TI  - A single intraperitoneal injection of endotoxin in rats induces long-lasting
      modifications in behavior and brain protein levels of TNF-alpha and IL-18.
AB  - BACKGROUND: Systemic inflammation might cause neuronal damage and sustain
      neurodegenerative diseases and behavior impairment, with the participation of pro
      inflammatory cytokines, like tumor necrosis factor (TNF)-alpha and interleukin
      (IL)-18. However, the potential contribution of these cytokines to behavioral
      impairment in the long-term period has not been fully investigated. METHODS:
      Wistar rats were treated with a single intraperitoneal injection of LPS (5 mg/kg)
      or vehicle. After 7 days and 10 months, the animal behavior was evaluated by
      testing specific cognitive functions, as mnesic, discriminative, and attentional
      functions, as well as anxiety levels. Contextually, TNF-alpha and IL-18 protein
      levels were measured by ELISA in defined brain regions (that is, frontal cortex,
      hippocampus, striatum, cerebellum, and hypothalamus). RESULTS: Behavioral testing
      demonstrated a specific and persistent cognitive impairment characterized by
      marked deficits in reacting to environment modifications, possibly linked to
      reduced motivational or attentional deficits. Concomitantly, LPS induced a TNF
      alpha increase in the hippocampus and frontal cortex (from 7 days onward) and
      cerebellum (only at 10 months). Interestingly, LPS treatment enhanced IL-18
      expression in these same areas only at 10 months after injection. CONCLUSIONS:
      Overall, these results indicate that the chronic neuroinflammatory network
      elicited by systemic inflammation involves a persistent participation of TNF
      alpha accompanied by a differently regulated contribution of IL-18. This leads to
      speculation that, though with still unclear mechanisms, both cytokines might take
      part in long-lasting modifications of brain functions, including behavioral
      alteration.

PMID- 22642745
TI  - SOX11 is useful in differentiating cyclin D1-positive diffuse large B-cell
      lymphoma from mantle cell lymphoma.
AB  - AIMS: To characterize the frequency and clinicopathological features of cyclin D1
      positive diffuse large B-cell lymphoma (DLBCL) and the usefulness of SOX11 in the
      differential diagnosis from mantle cell lymphoma (MCL). METHODS AND RESULTS: We
      retrospectively stained 206 consecutive DLBCLs for cyclin D1, and identified
      three (1.5%) positive cases, comprising two in the elderly with necrosis, and a
      third with a starry-sky pattern. All three cases shared the same non-germinal
      centre B-cell (non-GCB) phenotype [CD5-/CD10-/bcl-6+/MUM1+/SOX11-], Epstein-Barr
      virus (EBV) negativity, and absence of CCND1 aberrations by fluorescence in-situ
      hybridization. The third case showed both BCL6 and MYC rearrangements: a double
      hit lymphoma. In the same period there were 22 MCLs, all expressing cyclin D1,
      with 89% cases expressing SOX11, a frequency that is statistically different from
      cyclin D1-positive DLBCL. Notably, we identified a pleomorphic MCL initially
      misdiagnosed as DLBCL. A separate cohort of 98 DLBCL cases was negative for
      SOX11, with only one case expressing cyclin D1 with a GCB phenotype (CD10+/bcl
      6+/MUM1-). The two patients with tumour necrosis rapidly died of disease. The
      other two were in complete remission after immunochemotherapy. CONCLUSION: Cyclin
      D1-positive DLBCLs are rare, and they are negative for SOX11 or CCND1 aberration.
      SOX11 is useful in differentiating cyclin D1-positive DLBCL from MCL.

PMID- 22642750
TI  - Atomistic simulations of calcium uranyl(VI) carbonate adsorption on calcite and
      stepped-calcite surfaces.
AB  - Adsorption of actinyl ions onto mineral surfaces is one of the main mechanisms
      that control the migration of these ions in environmental systems. Here, we
      present computational classical molecular dynamics (MD) simulations to
      investigate the behavior of U(VI) in contact with different calcite surfaces. The
      calcium-uranyl-carbonate [Ca(2)UO(2)(CO(3))(3)] species is shown to display both
      inner- and outer-sphere adsorption to the flat {1014} and the stepped {3148} and
      {31216} planes of calcite. Free energy calculations, using the umbrella sampling
      method, are employed to simulate adsorption paths of the same uranyl species on
      the different calcite surfaces under aqueous condition. Outer-sphere adsorption
      is found to dominate over inner-sphere adsorption because of the high free energy
      barrier of removing a uranyl-carbonate interaction and replacing it with a new
      uranyl-surface interaction. An important binding mode is proposed involving a
      single vicinal water monolayer between the surface and the sorbed complex. From
      the free energy profiles of the different calcite surfaces, the uranyl complex
      was also found to adsorb preferentially on the acute-stepped {3148} face of
      calcite, in agreement with experiment.

PMID- 22642751
TI  - Therapeutic upregulation of Class A scavenger receptor member 5 inhibits tumor
      growth and metastasis.
AB  - Class A scavenger receptor member 5 (SCARA5) is a new member of the Class A
      scavenger receptors that has been proposed recently as a novel candidate tumor
      suppressor gene in human hepatocellular carcinoma. In the present study, we found
      that SCARA5 expression was frequently downregulated in various cancer cell lines
      and tumor samples. In addition, upregulation of SCARA5 expression in human cancer
      cell line (U251) led to a significant decrease in cell proliferation, clone
      formation, migration, and invasion in vitro. Furthermore, systemic treatment of
      tumor-bearing mice with SCARA5-cationic liposome complex not only reduced the
      growth of subcutaneous human glioma tumors, but also markedly suppressed the
      spontaneous formation of lung metastases. Similar results were obtained in
      another experiment using mice bearing experimental A549 lung metastases. Compared
      with the untreated control group, mice treated with SCARA5 exhibited reductions
      in both spontaneous U251 and experimental A549 lung metastases rates of 77.3% and
      70.2%, respectively. Western blot analysis was used to explore the molecular
      mechanisms involved and revealed that SCARA5 physically associated with focal
      adhesion kinase. Interestingly, upregulation of SCARA5 inactivated signal
      transducer and activator of transcription 3, as well as downstream signaling
      including cyclinB1, cyclinD1, AKT, survivin, matrix metalloproteinase-9 and
      vascular endothelial growth factor-A. Overall, the findings of the present study
      provide the first evidence that SCARA5 might be a promising target for the
      development of new antimetastatic agents for the gene therapy of cancer.

PMID- 22642752
TI  - Carbenylative amination with N-tosylhydrazones.
AB  - A Pd-catalyzed reaction of vinyl iodides and N-tosylhydrazones that assembles
      eta(3)-allyl ligands through carbene insertion is demonstrated. Intramolecular
      trapping with nitrogen nucleophiles generates good yields of cinnamyl and
      pentadienyl amines like those found in alkaloid natural products. Carbenylative
      amination was the key reaction to complete the synthesis of the alkaloid
      caulophyllumine B. Migratory insertion was biased to provide allylamines with
      optical purity up to 64% ee, but in a lower yield.

PMID- 22642753
TI  - Porous high-density polyethylene in facial reconstruction and revision
      rhinoplasty: a prospective cohort study.
AB  - INTRODUCTION: Initial methods which used human tissues as reconstruction
      materials caused different problems including rejection, limited shapes and
      infection. In 1970s, PHDPE (Medpor(r)) was introduced by its exclusive
      advantageous including no donor site morbidity, easily shaped and the minimal
      foreign body reaction. Hereby, we report our experience of using Medpor(r) in
      facial reconstruction especially in frontal reconstruction and orbital rim with a
      large sample size. METHODS: This study was a prospective cohort study. Surgical
      techniques included using Medpor(r) in reconstruction of lamina papiracea (LP)
      (15 patients), frontal bone (15 patients), orbital rim (18 patients) and open
      rhinoplasty (8 patients). All interventions on LP were performed by endoscopic
      procedures. All frontal operations were carried out by bicoronal incision. In
      orbital defects, we used subciliary incision. RESULTS: From all 56 patients, 1
      case had primitive neuroectodermal tumor (PNET) of maxillary sinus. In that case,
      reconstruction of inferior orbital rim was not successful and extrusion was
      occurred after radiotherapy. In rhinoplasty and other experiences no extrusion or
      infection were detected within the next 1 to 3 years of follow up. There were not
      any palpable and visible irregularities under the skin in our experiences.
      CONCLUSIONS: In this study the patients did not experience any complications
      during the follow up periods and the satisfaction was remarkable. Gathering these
      data gives rise to future review studies which can provide more organized
      evidences for replacing classic reconstructive methods by the presented material.

PMID- 22642754
TI  - Field effects induce bathochromic shifts in xanthene dyes.
AB  - There is ongoing interest in near-infrared (NIR) absorbing and emitting dyes for
      a variety of biomedical and materials applications. Simple and efficient
      synthetic procedures enable the judicious tuning of through-space polar (field)
      effects as well as low barrier hydrogen bonding to modulate the HOMO-LUMO gap in
      xanthene dyes. This affords unique NIR-absorbing xanthene chromophores.

PMID- 22642755
TI  - Changes in body weight and food choice in those attempting smoking cessation: a
      cluster randomised controlled trial.
AB  - BACKGROUND: Fear of weight gain is a barrier to smoking cessation and significant
      cause of relapse for many people. The provision of nutritional advice as part of
      a smoking cessation programme may assist some in smoking cessation and perhaps
      limit weight gain. The aim of this study was to determine the effect of a
      structured programme of dietary advice on weight change and food choice, in
      adults attempting smoking cessation. METHODS: Cluster randomised controlled
      design. Classes randomised to intervention commenced a 24-week intervention,
      focussed on improving food choice and minimising weight gain. Classes randomised
      to control received "usual care". RESULTS: Twenty-seven classes in Greater
      Glasgow were randomised between January and August 2008. Analysis, including
      those who continued to smoke, showed that actual weight gain and percentage
      weight gain was similar in both groups. Examination of data for those successful
      at giving up smoking showed greater mean weight gain in intervention subjects
      (3.9 (SD 3.1) vs. 2.7 (SD 3.7) kg). Between group differences were not
      significant (p = 0.23, 95% CI -0.9 to 3.5). In comparison to baseline improved
      consumption of fruit and vegetables and breakfast cereal were reported in the
      intervention group. A higher percentage of control participants continued smoking
      (74% vs. 66%). CONCLUSIONS: The intervention was not successful at minimising
      weight gain in comparison to control but was successful in facilitating some
      sustained improvements in the dietary habits of intervention participants.
      Improved quit rates in the intervention group suggest that continued contact with
      advisors may have reduced anxieties regarding weight gain and encouraged
      cessation despite weight gain. Research should continue in this area as evidence
      suggests that the negative effects of obesity could outweigh the health benefits
      achieved through reductions in smoking prevalence.

PMID- 22642756
TI  - Understanding Muslim patients: cross-cultural dental hygiene care.
AB  - BACKGROUND: Healthcare providers who understand the basic pillars of Islamic
      beliefs and common religious practices can apply these concepts, anticipate the
      needs of the Muslim patient and family, and attract Muslim patients to the
      practice. OBJECTIVE: Cross cultural knowledge can motivate dental hygienists to
      adopt culturally acceptable behaviors, strengthen patient-provider relationships
      and optimize therapeutic outcomes. Trends in Muslim population growth, Islamic
      history and beliefs, modesty practices, healthcare beliefs, contraception,
      childbearing, childrearing, pilgrimage, dietary practices, dental care
      considerations and communication are explained. MATERIALS AND METHODS: This paper
      reviews traditional Muslim beliefs and practices regarding lifestyle, customs,
      healthcare and religion as derived from the literature and study abroad
      experiences. RESULTS AND DISCUSSION: Recommendations are offered on how to blend
      western healthcare with Islamic practices when making introductions,
      appointments, eye contact, and selecting a practitioner. The significance of
      fasting and how dental hygiene care can invalidate the fast are also discussed.
      CONCLUSION: The ultimate goal is for practitioners to be culturally competent in
      providing care to Muslim patients, while keeping in mind that beliefs and
      practices can vary widely within a culture.

PMID- 22642757
TI  - Factors explaining the gender disparity in lipid-lowering treatment goal
      attainment rate in Chinese patients with statin therapy.
AB  - BACKGROUND: The lipid-lowering treatment goal attainment rate is lower for women
      than for men among Chinese patients, but the reasons for this disparity have not
      been fully explored yet. OBJECTIVES: To elucidate the potential factors and the
      significance of their contributions towards the observed discrepancy in lipid
      lowering treatment goal attainment rates between Chinese women and men. METHODS:
      We used data from 1808 patients from 21 tertiary and 6 secondary hospitals in
      China who received and maintained statin therapy treatment for at least 2 months.
      Lipid-lowering treatment goal attainment was defined as low-density lipoprotein
      cholesterol (LDL- C) reaching the treatment targets recommended by the Chinese
      Guidelines on Prevention and Control of Dyslipidemia in Adults. Logistic
      Regression was used to explore possible factors associated with gender disparity
      in goal attainment rates, and to what extent each factor contributes. RESULTS: A
      total of 674 women and 1134 men were enrolled in the study. Women had a
      significantly lower LDL-C goal attainment rate than that of men (46.0% vs 53.8%,
      P = 0.002), particularly in high and very high CVD risk groups. Among high and
      very high risk patients, approximately 35%, 7%, 5%, and 5% of gender disparity in
      LDL-C goal attainment rate was attributable to the gender difference in baseline
      LDL-C level, cardiovascular co-morbidities and associated risk factors,
      socioeconomic status, and the dosage of statin treatment, respectively.
      Approximately 50% of the gender disparity remained unexplained by these factors.
      CONCLUSIONS: Although nearly half of the gender disparity in lipid-lowering
      treatment goal attainment rate can be explained by the gender differences in
      baseline lipid level, socioeconomic status, cardiovascular co-morbidities and
      associated risk factors, and the dosage of statin in high and very high CVD risk
      patients, the other half of the gender disparity remains unexplained and requires
      further study to fully understand what other factors are at play.

PMID- 22642758
TI  - The influence of country of origin on engagement in self-care behaviours
      following heart surgery: a descriptive correlational study.
AB  - AIM: The aim of this study was to determine whether an individual's country of
      origin influenced performance of self-care behaviours after heart surgery.
      BACKGROUND: Patients are required to perform self-care behaviours following
      cardiovascular surgery. Usual care encompasses a patient education initiative
      that addresses self-care behaviour performance. Within Canada, current heart
      surgery patient education efforts have been designed and evaluated using
      homogenous samples that self-identify their country of origin as England, Ireland
      or Scotland. However, approximately 42.6% of Canadian cardiovascular surgical
      patients self-identify their country of origin as India or China. Thus, current
      cardiovascular surgery patient education initiatives may not be applicable to all
      patients undergoing heart surgery, which may result in decreased patient outcomes
      such as performance of self-care behaviours. DESIGN: This descriptive study.
      METHODS: A convenience sample of 90 patients who underwent heart surgery at one
      of two university-affiliated teaching hospitals, representing individuals of
      diverse backgrounds. Point-biserial correlational analysis was conducted to
      determine the relationship between country of origin and performance of self-care
      behaviours. RESULTS: Findings indicate individuals who self-identified their
      country of origin as England or Ireland were associated with a higher score on
      the number of self-care behaviours performed (p < 0.05) than individuals who self
      identified other countries of origin. Self-care behaviours were taught using
      patient education materials that were designed based on feedback obtained from
      individuals whose country of origin was England or Ireland. CONCLUSION: This
      study provides preliminary evidence to suggest country of origin influences the
      amount of self-care behaviours individuals will perform. RELEVANCE TO CLINICAL
      PRACTICE: Patient education initiatives should incorporate the values, beliefs,
      attitudes and customs reflective of an individual's country of origin to enhance
      the likelihood of producing desired outcomes.

PMID- 22642759
TI  - Evaluation of the performance of the N95-companion: effects of filter penetration
      and comparison with other aerosol instruments.
AB  - Fit factor is the ratio of the particle concentration outside (C(out)) to the
      inside (C(in)) of the respirator and assumes that filter penetration is
      negligible. For Class-95 respirators, concerns were raised that filter
      penetration could bias fit test measurements. The TSI N95-Companion was designed
      to overcome this limitation by measuring only 40-60 nm size particles. Recent
      research has shown that particles in this size range are the most penetrating for
      respirators containing electrostic filter media. The goal of this study was to
      better understand the performance of the N95-Companion by assessing the impact of
      filter penetration and by comparing C(out)/C(in) ratios measured by other aerosol
      instruments (nano-Differential Mobility Analyzer/Ultrafine Condensation Particle
      Counter (nano-DMA/UCPC) and the TSI PortaCount Plus) using N95 filtering
      facepiece respirators sealed to a manikin and with intentionally created leaks.
      Results confirmed that 40-60 nm-diameter size room air particles were most
      penetrating for the respirators tested. A nonlinear relationship was found
      between the N95-Companion-measured C(out)/C(in) ratios and the other instruments
      at the sealed condition and at the small leak sizes because the N95-Companion
      measures only charged particles that are preferentially captured by the
      electrostic filter media, while the other instrument configurations also measure
      uncharged particles, which are captured less efficiently. The C(out)/C(in) ratios
      from the N95-Companion for experiments conducted under sealed condition suggest
      that filter penetration of negatively charged 40-60 nm size particles was less
      than 0.05%. Thus, the N95-Companion measured C(out)/C(in) ratios are due
      primarily to particle penetration through leakage, not through filter media,
      while the C(out)/C(in) ratios for the PortaCount, nano-DMA/UCPC, and UCPC result
      from a combination of face seal leakage and filter penetration.

PMID- 22642761
TI  - Addendum.

PMID- 22642760
TI  - Studying forced expiratory volume at 1 second over menstrual segments in
      asthmatic and non-asthmatic women: assessing protocol feasibility.
AB  - BACKGROUND: Sex hormones may play an important role in observed gender
      differences in asthma incidence and severity, as well as in the observed changes
      in asthma symptoms during times of hormonal fluctuation (i.e.; premenstrual,
      pregnancy, etc.). This pilot study sought to demonstrate the feasibility of data
      collection methods to investigate the effects of sex hormones on lung function in
      women. FINDINGS: A cohort of 13 women (6 with and 7 without prior asthma
      diagnoses) who were having menstrual periods and were not taking hormones
      collected urine samples daily for measurement of estrogen (estrone E1C) and
      progesterone (Pregnanediol-glucuronide PDG) metabolites over the course of a
      menstrual segment (bleeding episode plus the following bleeding-free interval).
      Hormones were used to estimate menstrual segment phase (follicular versus luteal)
      based on a published algorithm. Daily bleeding and FEV1 measurements were
      recorded and percent predicted FEV1 was calculated. Percent predicted FEV1
      decreased over the course of the follicular but not the luteal phase. More
      specifically, among women without a prior asthma diagnosis, the E1C/PDG ratio and
      E1C and PDG were individually associated with FEV1 in the follicular phase. No
      associations were found between hormones and percent predicted FEV1 in the luteal
      phase or among asthmatic women. E1C was associated with FEV1 in the five days
      before bleeding onset only among non-asthmatic women. DISCUSSION: A study of
      contiguous daily hormones and symptoms over menstrual segments from a large group
      of women with and without asthma is needed to better determine within-woman
      cyclicity of the observed patterns.

PMID- 22642763
TI  - Biological Structure and Dynamics: Volumes One and Two.

PMID- 22642764
TI  - The Journal of Biomolecular Structure and Dynamics Establishes Web Site: The JBSD
      WWW Edition.

PMID- 22642765
TI  - Cancer Watch Establishes Web Site: The CANCER WATCH WWW Edition.

PMID- 22642766
TI  - Variable performance of commercial epidermal growth factor receptor antibodies in
      detection of basal-like breast cancer.

PMID- 22642767
TI  - A new prognostic classification for overall survival in Asian patients with
      previously untreated metastatic renal cell carcinoma.
AB  - The aims of the present study were to: (i) develop a clinically useful prognostic
      classification in Asian patients with metastatic renal cell carcinoma (RCC) by
      combining metastatic features with several pretreatment parameters; and (ii)
      evaluate the validity of this prognostic classification. Baseline characteristics
      and outcomes were collected for 361 patients who underwent interferon-alpha-based
      therapy between 1995 and 2005. Relationships between overall survival (OS) and
      potential prognostic factors were assessed using Cox's proportional hazard model.
      The predictive performance of the model was evaluated using bootstrap resampling
      procedures and by using an independent dataset obtained from randomly selected
      institutions. The predictive accuracy was measured using the concordance index (c
      index). Four factors were identified as independent prognostic factors: time from
      initial diagnosis to treatment, anemia, elevated lactate dehydrogenase (LDH), and
      poor prognostic metastatic group (liver only, bone only, or multiple organ
      metastases). Each patient was assigned to one of three risk groups: favorable
      risk (none or one factor; n = 120), in which median OS was 51 months;
      intermediate risk (two factors; n = 101), in which median OS was 21 months; and
      poor risk (three or four factors; n = 102), in which median OS was 10 months. The
      c-index was 0.72 in the original dataset and 0.72 in 500 random bootstrap
      samples. In the independent dataset for external validation, the c-index was
      0.73. Thus, the new prognostic classification is easily applicable for Asian
      patients with previously untreated metastatic RCC and should be incorporated into
      patient care, as well as clinical trials performed in Asia.

PMID- 22642768
TI  - Biomechanics of the press-fit phenomenon in dental implantology: an image-based
      finite element analysis.
AB  - BACKGROUND: A fundamental pre-requisite for the clinical success in dental
      implant surgery is the fast and stable implant osseointegration. The press-fit
      phenomenon occurring at implant insertion induces biomechanical effects in the
      bone tissues, which ensure implant primary stability. In the field of dental
      surgery, the understanding of the key factors governing the osseointegration
      process still remains of utmost importance. A thorough analysis of the
      biomechanics of dental implantology requires a detailed knowledge of bone
      mechanical properties as well as an accurate definition of the jaw bone geometry.
      METHODS: In this work, a CT image-based approach, combined with the Finite
      Element Method (FEM), has been used to investigate the effect of the drill size
      on the biomechanics of the dental implant technique. A very accurate model of the
      human mandible bone segment has been created by processing high resolution micro
      CT image data. The press-fit phenomenon has been simulated by FE analyses for
      different common drill diameters (DA=2.8 mm, DB=3.3 mm, and DC=3.8 mm) with depth
      L=12 mm. A virtual implant model has been assumed with a cylindrical geometry
      having height L=11 mm and diameter D=4 mm. RESULTS: The maximum stresses
      calculated for drill diameters DA, DB and DC have been 12.31 GPa, 7.74 GPa and
      4.52 GPa, respectively. High strain values have been measured in the cortical
      area for the models of diameters DA and DB, while a uniform distribution has been
      observed for the model of diameter DC . The maximum logarithmic strains,
      calculated in nonlinear analyses, have been epsilon=2.46, 0.51 and 0.49 for the
      three models, respectively. CONCLUSIONS: This study introduces a very powerful,
      accurate and non-destructive methodology for investigating the effect of the
      drill size on the biomechanics of the dental implant technique.Further studies
      could aim at understanding how different drill shapes can determine the optimal
      press-fit condition with an equally distributed preload on both the cortical and
      trabecular structure around the implant.

PMID- 22642769
TI  - Dual-emitting quantum dot/quantum rod-based nanothermometers with enhanced
      response and sensitivity in live cells.
AB  - Temperature is a key parameter in physiological processes, and probes able to
      detect small changes in local temperature are necessary for accurate and
      quantitative physical descriptions of cellular events. Several have recently
      emerged that offer excellent temperature sensitivity, spatial resolution, or
      cellular compatibility, but it has been challenging to realize all of these
      properties in a single construct. Here, we introduce a luminescent nanocrystal
      based sensor that achieves this with a 2.4% change/ degrees C ratiometric
      response over physiological temperatures in aqueous buffers, with a precision of
      at least 0.2  degrees C. Thermoresponsive dual emission is conferred by a Forster
      resonant energy transfer (FRET) process between CdSe-CdS quantum dot-quantum rods
      (QD-QRs) as donors and cyanine dyes as acceptors, which are conjugated to QD-QRs
      using an amphiphilic polymer coating. The nanothermometers were delivered to live
      cells using a pH-responsive cationic polymer colloid, which served to both
      improve uptake and release nanocrystals from endosomal confinement. Within cells,
      they showed an unexpected enhancement in their temperature response and
      sensitivity, highlighting the need to calibrate these and similar probes within
      the cell.

PMID- 22642770
TI  - "Health divide" between indigenous and non-indigenous populations in Kerala,
      India: population based study.
AB  - BACKGROUND: The objective of this study is to investigate the magnitude and
      nature of health inequalities between indigenous (Scheduled Tribes) and non
      indigenous populations, as well as between different indigenous groups, in a
      rural district of Kerala State, India. METHODS: A health survey was carried out
      in a rural community (N = 1660 men and women, 18-96 years). Age- and sex
      standardised prevalence of underweight (BMI < 18.5 kg/m2), anaemia, goitre,
      suspected tuberculosis and hypertension was compared across forward castes, other
      backward classes and tribal populations. Multi-level weighted logistic regression
      models were used to estimate the predicted prevalence of morbidity for each age
      and social group. A Blinder-Oaxaca decomposition was used to further explore the
      health gap between tribes and non-tribes, and between subgroups of tribes.
      RESULTS: Social stratification remains a strong determinant of health in the
      progressive social policy environment of Kerala. The tribal groups are bearing a
      higher burden of underweight (46.1 vs. 24.3%), anaemia (9.9 vs. 3.5%) and goitre
      (8.5 vs. 3.6%) compared to non-tribes, but have similar levels of tuberculosis
      (21.4 vs. 20.4%) and hypertension (23.5 vs. 20.1%). Significant health
      inequalities also exist within tribal populations; the Paniya have higher levels
      of underweight (54.8 vs. 40.7%) and anaemia (17.2 vs. 5.7%) than other Scheduled
      Tribes. The social gradient in health is evident in each age group, with the
      exception of hypertension. The predicted prevalence of underweight is 31 and 13
      percentage points higher for Paniya and other Scheduled Tribe members,
      respectively, compared to Forward Caste members 18-30 y (27.1%). Higher
      hypertension is only evident among Paniya adults 18-30 y (10 percentage points
      higher than Forward Caste adults of the same age group (5.4%)). The decomposition
      analysis shows that poverty and other determinants of health only explain 51% and
      42% of the health gap between tribes and non-tribes for underweight and goitre,
      respectively. CONCLUSIONS: Policies and programmes designed to benefit the
      Scheduled Tribes need to promote their well-being in general but also target the
      specific needs of the most vulnerable indigenous groups. There is a need to
      enhance the capacity of the disadvantaged to equally take advantage of health
      opportunities.

PMID- 22642772
TI  - CCSD(T) study of CD3-O-CD3 and CH3-O-CD3 far-infrared spectra.
AB  - From a vibrationally corrected 3D potential energy surface determined with highly
      correlated ab initio calculations (CCSD(T)), the lowest vibrational energies of
      two dimethyl-ether isotopologues, (12)CH(3)-(16)O-(12)CD(3) (DME-d(3)) and
      (12)CD(3)-(16)O-(12)CD(3) (DME-d(6)), are computed variationally. The levels that
      can be populated at very low temperatures correspond to the COC-bending and the
      two methyl torsional modes. Molecular symmetry groups are used for the
      classification of levels and torsional splittings. DME-d(6) belongs to the G(36)
      group, as the most abundant isotopologue (12)CH(3)-(16)O-(12)CH(3) (DME-h(6)),
      while DME-d(3) is a G(18) species. Previous assignments of experimental Raman and
      far-infrared spectra are discussed from an effective Hamiltonian obtained after
      refining the ab initio parameters. Because a good agreement between calculated
      and experimental transition frequencies is reached, new assignments are proposed
      for various combination bands corresponding to the two deuterated isotopologues
      and for the 020 -> 030 transition of DME-d(6). Vibrationally corrected potential
      energy barriers, structural parameters, and anharmonic spectroscopic parameters
      are provided. For the 3N - 9 neglected vibrational modes, harmonic and anharmonic
      fundamental frequencies are obtained using second-order perturbation theory by
      means of CCSD and MP2 force fields. Fermi resonances between the COC-bending and
      the torsional modes modify DME-d(3) intensities and the band positions of the
      torsional overtones.

PMID- 22642773
TI  - Additive and competitive effects of bacteria and Mn oxides on arsenite oxidation
      kinetics.
AB  - Arsenic (As) is a redox-active metalloid whose toxicity and mobility in soil
      depend on oxidation state. Arsenite [As(III)] can be oxidized to arsenate [As(V)]
      by both minerals and microbes in soil however, the interaction between these
      abiotic and biotic processes is not well understood. In this study, the time
      dependency of As(III) oxidation by two heterotrophic soil bacteria (Agrobacterium
      tumefaciens and Pseudomonas fluorescens) and a poorly crystalline manganese (Mn)
      oxide mineral (delta-MnO(2)) was determined using batch experiments. The apparent
      rate of As(V) appearance in solution was greater for the combined batch
      experiments in which bacteria and delta-MnO(2) were oxidizing As(III) at the same
      time than for either component alone. The additive effect of the mixed cell-
      delta-MnO(2) system was consistent for short (<1 h) and long (24 h) term
      coincubation indicating that mineral surface inhibition by cells has little
      effect the As(III) oxidation rate. Surface interactions between cells and the
      mineral surface were indicated by sorption and pH-induced desorption results.
      Total sorption of As on the mineral was lower with bacteria present (16.1 +/-
      0.8% As sorbed) and higher with delta-MnO(2) alone (23.4 +/- 1%) and As was more
      easily desorbed from the cell-delta-MnO(2) system than from delta-MnO(2) alone.
      Therefore, the presence of bacteria inhibited As sorption and decreased the
      stability of sorbed As on delta-MnO(2) even though As(III) was oxidized fastest
      in a mixed cell-delta-MnO(2) system. The additive effect of biotic (As-oxidizing
      bacteria) and abiotic (delta-MnO(2) mineral) oxidation processes in a system
      containing both oxidants suggests that mineral-only results may underestimate the
      oxidative capacity of natural systems with biotic and abiotic As(III) oxidation
      pathways.

PMID- 22642774
TI  - Reducing drinking water supply chemical contamination: risks from underground
      storage tanks.
AB  - Drinking water supplies are at risk of contamination from a variety of physical,
      chemical, and biological sources. Ranked among these threats are hazardous
      material releases from leaking or improperly managed underground storage tanks
      located at municipal, commercial, and industrial facilities. To reduce human
      health and environmental risks associated with the subsurface storage of
      hazardous materials, government agencies have taken a variety of legislative and
      regulatory actions--which date back more than 25 years and include the
      establishment of rigorous equipment/technology/operational requirements and
      facility-by-facility inspection and enforcement programs. Given a history of more
      than 470,000 underground storage tank releases nationwide, the U.S. Environmental
      Protection Agency continues to report that 7,300 new leaks were found in federal
      fiscal year 2008, while nearly 103,000 old leaks remain to be cleaned up. In this
      article, we report on an alternate evidence-based intervention approach for
      reducing potential releases from the storage of petroleum products (gasoline,
      diesel, kerosene, heating/fuel oil, and waste oil) in underground tanks at
      commercial facilities located in Rhode Island. The objective of this study was to
      evaluate whether a new regulatory model can be used as a cost-effective
      alternative to traditional facility-by-facility inspection and enforcement
      programs for underground storage tanks. We conclude that the alternative model,
      using an emphasis on technical assistance tools, can produce measurable
      improvements in compliance performance, is a cost-effective adjunct to
      traditional facility-by-facility inspection and enforcement programs, and has the
      potential to allow regulatory agencies to decrease their frequency of inspections
      among low risk facilities without sacrificing compliance performance or
      increasing public health risks.

PMID- 22642771
TI  - Telmisartan directly ameliorates the neuronal inflammatory response to IL-1beta
      partly through the JNK/c-Jun and NADPH oxidase pathways.
AB  - BACKGROUND: Blockade of angiotensin II type 1 (AT1) receptors ameliorates brain
      inflammation, and reduces excessive brain interleukin-1 beta (IL-1beta)
      production and release from cortical microglia. The aim of this study was to
      determine whether, in addition, AT1 receptor blockade directly attenuates IL
      1beta-induced inflammatory responses in neuronal cultures. METHODS: SK-N-SH human
      neuroblasts and primary rat cortical neurons were pretreated with telmisartan
      followed by exposure to IL-1beta. Gene expression was determined by reverse
      transcriptase (RT)-PCR, protein expression and kinase activation by western
      blotting, NADPH oxidase activity by the lucigenin method, prostaglandin E2 (PGE2)
      release by enzyme immunoassay, reactive oxygen species (ROS) generation by the
      dichlorodihydrofluorescein diacetate fluorescent probe assay, and peroxisome
      proliferator-activated receptor gamma (PPARgamma) involvement was assessed with
      the antagonists GW9662 and T0070907, the agonist pioglitazone and the expression
      of PPARgamma target genes ABCG1 and CD36. RESULTS: We found that SK-N-SH
      neuroblasts expressed AT1 but not AT2 receptor mRNA. Telmisartan reduced IL-1beta
      induced cyclooxygenase-2 (COX-2) expression and PGE2 release more potently than
      did candesartan and losartan. Telmisartan reduced the IL-1beta-induced increase
      in IL-1R1 receptor and NADPH oxidase-4 (NOX-4) mRNA expression, NADPH oxidase
      activity, and ROS generation, and reduced hydrogen peroxide-induced COX-2 gene
      expression. Telmisartan did not modify IL-1beta-induced ERK1/2 and p38 mitogen
      activated protein kinase (MAPK) phosphorylation or nuclear factor-kappaB
      activation but significantly decreased IL-1beta-induced c-Jun N-terminal kinase
      (JNK) and c-Jun activation. The JNK inhibitor SP600125 decreased IL-1beta-induced
      PGE2 release with a potency similar to that of telmisartan. The PPARgamma agonist
      pioglitazone reduced IL-1beta-induced inflammatory reaction, whereas telmisartan
      did not activate PPARgamma, as shown by its failure to enhance the expression of
      the PPARgamma target genes ABCG1 and CD36, and the inability of the PPARgamma
      antagonists GW9662 and T0070907 to modify the effect of telmisartan on COX-2
      induction. The effect of telmisartan on IL-1beta-stimulated COX-2 and IL-1R1 mRNA
      expression and ROS production was replicated in primary rat cortical neurons.
      CONCLUSIONS: Telmisartan directly ameliorates IL-1beta-induced neuronal
      inflammatory response by inhibition of oxidative stress and the JNK/c-Jun
      pathway. Our results support the hypothesis that AT1 receptor blockers are
      directly neuroprotective, and should be considered for the treatment of
      inflammatory conditions of the brain.

PMID- 22642776
TI  - Optimizing pharmacotherapy in older patients: a European perspective.

PMID- 22642777
TI  - Off-label prescribing in older patients.
AB  - The practice of off-label prescribing, i.e. prescribing drugs either for
      unregistered/unapproved therapeutic indications and age groups or using
      unregistered/unapproved doses or methods of administration, is common in older
      patients. This may be due to the poor representation of this group in pre
      marketing clinical trials assessing therapeutic efficacy and safety of novel
      therapies or merely to the fact that trials in a particular indication have not
      been undertaken. Off-label prescribing should not be viewed as scientifically or
      ethically unsound when there are good clinical data to support a particular
      therapeutic indication. However, a number of steps should be followed in order to
      ensure therapeutic efficacy, reducing, at the same time, the risk of adverse drug
      reactions and/or medical litigation. This article discusses the current
      epidemiology and trends in off-label prescribing in older patients, the
      scientific and ethical justification of this practice, medico-legal implications,
      and proposed strategies for risk mitigation.

PMID- 22642778
TI  - Off-label prescribing in older people: the need for increased awareness and
      caution.

PMID- 22642779
TI  - Inappropriate prescribing: criteria, detection and prevention.
AB  - Inappropriate prescribing is highly prevalent in older people and is a major
      healthcare concern because of its association with negative healthcare outcomes
      including adverse drug events, related morbidity and hospitalization. With
      changing population demographics resulting in increasing proportions of older
      people worldwide, improving the quality and safety of prescribing in older people
      poses a global challenge. To date a number of different strategies have been used
      to identify potentially inappropriate prescribing in older people. Over the last
      two decades, a number of criteria have been published to assist prescribers in
      detecting inappropriate prescribing, the majority of which have been explicit
      sets of criteria, though some are implicit. The majority of these prescribing
      indicators pertain to overprescribing and misprescribing, with only a minority
      focussing on the underprescribing of indicated medicines. Additional
      interventions to optimize prescribing in older people include comprehensive
      geriatric assessment, clinical pharmacist review, and education of prescribers as
      well as computerized prescribing with clinical decision support systems. In this
      review, we describe the inappropriate prescribing detection tools or criteria
      most frequently cited in the literature and examine their role in preventing
      inappropriate prescribing and other related healthcare outcomes. We also discuss
      other measures commonly used in the detection and prevention of inappropriate
      prescribing in older people and the evidence supporting their use and their
      application in everyday clinical practice.

PMID- 22642780
TI  - Adverse drug reactions in older people: detection and prevention.
AB  - Adverse drug reactions (ADRs) in older adults are an important healthcare problem
      since they are frequently a cause of hospitalization, occur commonly during
      admission, and are an important cause of morbidity and mortality. Older adults
      are particularly susceptible to ADRs because they are usually on multiple drug
      regimens and because age is associated with changes in pharmacokinetics and
      pharmacodynamics. The presentation of an ADR in older adults is often atypical,
      which further complicates its recognition. One potential strategy for improving
      recognition of ADRs is to identify those patients who are at risk of an ADR. The
      recently developed GerontoNet ADR Risk Score is a practical tool for
      identification of older patients who are at increased risk for an ADR and who may
      represent a target for interventions aimed at reducing ADRs. Provision of
      adequate education in the domain of clinical geriatric pharmacology can improve
      recognition of ADRs. Besides formal surveillance systems, built-in computer
      programs with electronic prescribing databases and clinical pharmacist
      involvement in patient care within multidisciplinary geriatric teams might help
      to minimize the occurrence of ADRs. In addition, a number of actions can be taken
      in hospitals to stimulate appropriate prescribing and to assure adequate
      communication between primary and hospital care. In older adults with complex
      medical problems and needs, a global evaluation obtained through a comprehensive
      geriatric assessment may be helpful in simplifying drug prescription and
      prioritizing pharmacological and healthcare needs, resulting in an improvement in
      quality of prescribing.

PMID- 22642781
TI  - Underprescription of beneficial medicines in older people: causes, consequences
      and prevention.
AB  - Underprescription of potentially useful drugs is widespread among older people
      and may herald several adverse outcomes. We aimed to review the evidence
      pertaining to the epidemiology, causes and consequences of underprescribing, as
      well as recent advances in the development of interventions able to reduce
      underprescribing and improve outcomes in older people. Underprescribing is highly
      prevalent across different settings, including in the community, hospitals and
      nursing homes. Multimorbidity, polypharmacy, ageism, lack of scientific evidence,
      fear of adverse events and economic problems may contribute to the
      underprescription of indicated drugs, although in some patients, a limited life
      expectancy, the lack of a favourable risk-to-benefit ratio or a patient's refusal
      might represent appropriate reasons not to prescribe a drug. Selected
      interventions may help to improve the quality of prescriptions and reduce the
      burden of underprescribing. Among these, comprehensive geriatric assessment (CGA)
      has been demonstrated to effectively improve prescribing practice. Interventions
      based on service delivery changes, such as those that include a clinical
      pharmacist or a case manager in the process of care, were also found to improve
      the quality of pharmacological prescriptions. Educational interventions may also
      be effective in reducing underprescribing. More recently, the clinical
      application of the Screening Tool to Alert Doctors to Right Treatment (START)
      criteria has been able to significantly reduce underprescribing. Since START
      criteria are easier to apply in clinical practice than other instruments, it is
      conceivable that their systematic use may contribute to reducing underprescribing
      and to improving health outcomes in older patients.

PMID- 22642782
TI  - Evidence-based strategies for the optimization of pharmacotherapy in older
      people.
AB  - Geriatric pharmacotherapy represents one of the biggest achievements of modern
      medical interventions. However, geriatric pharmacotherapy is a complex process
      that encompasses not only drug prescribing but also age-appropriate drug
      development and manufacturing, appropriate drug testing in clinical trials,
      rational and safe prescribing, reliable administration and assessment of drug
      effects, including adherence measurement and age-appropriate outcomes monitoring.
      During this complex process, errors can occur at any stage, and intervention
      strategies to improve geriatric pharmacotherapy are targeted at improving the
      regulatory processes of drug testing, reducing inappropriate prescribing,
      preventing beneficial drug underuse and use of potentially harmful drugs, and
      preventing adverse drug interactions. The aim of this review is to provide an
      update on selected recent developments in geriatric pharmacotherapy, including
      age discrimination in drug trials, a new healthcare professional qualification
      and shared competence in geriatric drug therapy, the usefulness of information
      and communication technologies, and pharmacogenetics. We also review optimizing
      strategies aimed at medication adherence focusing on complex elderly patients.
      Among the current information technologies, there is sufficient evidence that
      computerized decision-making support systems are modestly but significantly
      effective in reducing inappropriate prescribing and adverse drug events across
      healthcare settings. The majority of interventions target physicians, for whom
      the scientific concept of appropriate prescribing and the acceptability of the
      alert system used play crucial roles in the intervention's success. For
      prescribing optimization, results of educational intervention strategies were
      inconsistent. The more promising strategies involved pharmacists or
      multidisciplinary teams including geriatric medicine services. However,
      methodological weaknesses including population and intervention heterogeneity do
      not allow for comprehensive meta-analyses to determine the clinical value of
      individual approaches. In relation to drug adherence, a recent meta-analysis of
      33 randomized clinical trials in older patients found behavioural interventions
      had significant effects, and these interventions were more effective than
      educational interventions. For patients with multiple conditions and
      polypharmacy, successful interventions included structured medication review,
      medication regimen simplification, administration aids and medication reminders,
      but no firm conclusion in favour of any particular intervention could be made.
      Interventions to optimize geriatric pharmacotherapy focused most commonly on
      pharmacological outcomes (drug appropriateness, adverse drug events, adherence),
      providing only limited information about clinical outcomes in terms of health
      status, morbidity, functionality and overall healthcare costs. Little attention
      was given to psychosocial and behavioural aspects of pharmacotherapy. There is
      sufficient potential for improvements in geriatric pharmacotherapy in terms of
      drug safety and effectiveness. However, just as we require evidence-based, age
      specific, pharmacological information for efficient clinical decision making, we
      need solid evidence for strategies that consistently improve the quality of
      pharmacological treatments at the health system level to shape 'age-attuned'
      health and drug policy.

PMID- 22642783
TI  - The role of the pharmacist in optimizing pharmacotherapy in older people.
AB  - Prescription of medicines is a fundamental component of the care of older people,
      but evidence suggests that pharmacotherapy in this population is often
      inappropriate. Pharmacists have been involved in different approaches for the
      optimization of prescribing and rational medication use in older people. This
      article describes the different models of care in which pharmacists are involved
      in the optimization of pharmacotherapy in older people, and reviews the impact of
      these approaches on both process and outcome measures. The provision of
      pharmaceutical care, medication reviews and educational interventions by
      pharmacists in the nursing home, ambulatory and acute care settings are
      discussed. We selected systematic reviews, reviews and original studies, and for
      the latter, we focused more specifically on European publications published
      between 2001 and 2011. From the literature reviewed, it is clear that when
      pharmacists play a proactive role in performing medication reviews and in the
      active education of other healthcare professionals, pharmacotherapy for older
      patients is improved. However, the evidence of the impact of pharmacists'
      interventions on health outcomes, quality of life or cost effectiveness of care
      is mixed. Better results have been reported when pharmacists are skilled and work
      in the context of a multidisciplinary team. Opportunities remain for multicentre,
      European-based, pharmacist-intervention trials in all settings, to determine the
      effectiveness and economic benefit of pharmacist involvement in the optimization
      of pharmacotherapy in older people.

PMID- 22642785
TI  - Blood pressure variables and prevalent electrocardiographic left ventricular
      hypertrophy in sub-Saharan African individuals with type 2 diabetes.
AB  - BACKGROUND: The aim of the present study was to investigate whether brachial
      blood pressure (BP) variables (systolic BP [SBP], diastolic BP [DBP], pulse [PP]
      and mean arterial pressure [MAP]) are similar determinants of prevalent
      electrocardiographic left ventricular hypertrophy (LVH) in sub-Saharan Africans
      with type 2 diabetes (T2D). METHODS: The study included 420 individuals (49% men)
      with T2D who were receiving chronic care in two main referral centers in the two
      major cities (Douala and Yaounde) of Cameroon. Logistic regression models were
      used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for a
      standard deviation (SD) higher level of SBP (25 mmHg), DBP (13), PP (18) and MAP
      (20) with the risk of LVH. Discrimination was assessed and compared with c
      statistics and relative integrated discrimination improvement (RIDI; %). RESULTS:
      The multivariable adjusted OR (95% CI) for prevalent LVH with each SD higher
      pressure variable was 1.61 (1.22-2.11) for SBP, 1.27 (0.99-1.63) for DBP, 1.62
      (1.23-2.15) for PP and 1.44 (1.11-1.87) for MAP. Comparison of c-statistics
      revealed no difference in the discrimination power of models with each of the BP
      variables (P > 0.09). However, RIDI showed enhanced discrimination in the models
      when other BP variables were replaced with PP. However, this enhancement was
      marginal for SBP. Using BP combinations modestly improved discrimination.
      CONCLUSIONS: The best predictors of prevalent LVH in the present study population
      were PP and SBP, whereas DBP was the least effective predictor. These findings
      have implications for cardiovascular risk stratification and monitoring of risk
      reducing therapies.

PMID- 22642784
TI  - Drug therapy optimization at the end of life.
AB  - Older people reaching end-of-life status are particularly at risk of adverse
      effects of drug therapy. Polypharmacy, declining organ function, co-morbidity,
      malnutrition, cachexia and changes in body composition all sum up to increase the
      risk of many drug-related problems in individuals who receive end-of-life care.
      End of life is defined by a limited lifespan or advanced disability. Optimal
      prescribing for end-of-life patients with multimorbidity, especially in those
      dying from non-cancer conditions, remains mostly unexplored, despite the
      increasing recognition that the management goals for patients with chronic
      diseases should be redefined in the setting of reduced life expectancy. Most
      drugs used for symptom palliation in end-of-life care of older patients are used
      without solid evidence of their benefits and risks in this particularly frail
      population. Appropriate dosing or optimal administration routes are in most cases
      unknown. Avoiding or discontinuing drugs that aim to prolong life or prevent
      disability is usually common sense in end-of-life care, particularly when the
      time needed to obtain the expected benefits from the drug is longer than the life
      expectancy of a particular individual. However, discontinuation of drugs is not
      standard practice, and prescriptions are usually not adapted to changes in the
      course of advanced diseases. Careful consideration of remaining life expectancy,
      time until benefit, goals of care and treatment targets for each drug seems to be
      a sensible framework for decision making. In this article, some key issues on
      drug therapy at the end of life are discussed, including principles of decision
      making about drug treatments, specific aspects of drug therapy in some common
      geriatric conditions (heart failure and dementia), treatment of acute concurrent
      problems such as infections, evidence to guide the choice and use of drugs to
      treat symptoms in palliative care, and avoidance of some long-term therapies in
      end-of-life care. Solid evidence is lacking to guide optimal pharmacotherapy in
      most end-of-life settings, especially in non-cancer diseases and very old
      patients. Some open questions for research are suggested.

PMID- 22642786
TI  - Spontaneous pneumocephalus presenting with alien limb phenomena.
AB  - BACKGROUND: Spontaneous pneumocephalus is a rare condition that has been reported
      infrequently. Alien limb syndrome is an uncommon phenomenon most often seen in
      patients with frontal and callosal lesions. METHOD: Case report of a patient with
      pneumocephalus presenting with alien limb syndrome. The patient underwent
      successful surgical management. A literature review and discussion of aspects of
      this presentation are also included. CONCLUSION: In this case, a spontaneous
      pneumocephalus has formed a frontal space-occupying lesion and presented with
      alien limb phenomena.

PMID- 22642787
TI  - Menhaden oil, but not safflower or soybean oil, aids in restoring the
      polyunsaturated fatty acid profile in the novel delta-6-desaturase null mouse.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFA) have diverse biological effects,
      from promoting inflammation to preventing cancer and heart disease. Growing
      evidence suggests that individual PUFA may have independent effects in health and
      disease. The individual roles of the two essential PUFA, linoleic acid (LA) and
      alpha-linolenic acid (ALA), have been difficult to discern from the actions of
      their highly unsaturated fatty acid (HUFA) downstream metabolites. This issue has
      recently been addressed through the development of the Delta-6 desaturase knock
      out (D6KO) mouse, which lacks the rate limiting Delta-6 desaturase enzyme and
      therefore cannot metabolize LA or ALA. However, a potential confounder in this
      model is the production of novel Delta-5 desaturase (D5D) derived fatty acids
      when D6KO mice are fed diets containing LA and ALA, but void of arachidonic acid.
      OBJECTIVE: The aim of the present study was to characterize how the D6KO model
      differentially responds to diets containing the essential n-6 and n-3 PUFA, and
      whether the direct provision of downstream HUFA can rescue the phenotype and
      prevent the production of D5D fatty acids. METHODOLOGY: Liver and serum
      phospholipid (PL) fatty acid composition was examined in D6KO and wild type mice
      fed i) 10% safflower oil diet (SF, LA rich) ii) 10% soy diet (SO, LA+ALA) or iii)
      3% menhaden oil +7% SF diet (MD, HUFA rich) for 28 days (n = 3-7/group). RESULTS:
      Novel D5D fatty acids were found in liver PL of D6KO fed SF or SO-fed mice, but
      differed in the type of D5D fatty acid depending on diet. Conversely, MD-fed D6KO
      mice had a liver PL fatty acid profile similar to wild-type mice. CONCLUSIONS:
      Through careful consideration of the dietary fatty acid composition, and
      especially the HUFA content in order to prevent the synthesis of D5D fatty acids,
      the D6KO model has the potential to elucidate the independent biological and
      health effects of the parent n-6 and n-3 fatty acids, LA and ALA.

PMID- 22642788
TI  - Hormone replacement therapy is associated with gastro-oesophageal reflux disease:
      a retrospective cohort study.
AB  - BACKGROUND: Oestrogen and progestogen have the potential to influence gastro
      intestinal motility; both are key components of hormone replacement therapy
      (HRT). Results of observational studies in women taking HRT rely on self
      reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal
      reflux disease (GORD) remains unclear. This study investigated the association
      between HRT and GORD in menopausal women using validated general practice
      records. METHODS: 51,182 menopausal women were identified using the UK General
      Practice Research Database between 1995-2004. Of these, 8,831 were matched with
      and without hormone use. Odds ratios (ORs) were calculated for GORD and proton
      pump inhibitor (PPI) use in hormone and non-hormone users, adjusting for age, co
      morbidities, and co-pharmacy. RESULTS: In unadjusted analysis, all forms of
      hormone use (oestrogen-only, tibolone, combined HRT and progestogen) were
      statistically significantly associated with GORD. In adjusted models, this
      association remained statistically significant for oestrogen-only treatment (OR
      1.49; 1.18-1.89). Unadjusted analysis showed a statistically significant
      association between PPI use and oestrogen-only and combined HRT treatment. When
      adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95%
      CI 1.03-1.74). Findings from the adjusted model demonstrated the greater use of
      PPI by progestogen users (OR 1.50; 1.01-2.22). CONCLUSIONS: This first large
      cohort study of the association between GORD and HRT found a statistically
      significant association between oestrogen-only hormone and GORD and PPI use. This
      should be further investigated using prospective follow-up to validate the
      strength of association and describe its clinical significance.

PMID- 22642789
TI  - The clinical effectiveness and cost-effectiveness of low-intensity psychological
      interventions for the secondary prevention of relapse after depression: a
      systematic review.
AB  - BACKGROUND: Depression is the most common mental disorder in community settings
      and a major cause of disability across the world. The objective of treatment is
      to achieve remission or at least adequate control of depressive symptoms;
      however, even after successful treatment, the risk of relapse after remission is
      significant. Although the effectiveness of low-intensity interventions has been
      extensively evaluated to treat primary symptoms of psychological difficulties,
      there has been substantially less research examining the use of these
      interventions as a relapse prevention strategy. OBJECTIVE: To systematically
      review the clinical effectiveness and cost-effectiveness of low-intensity
      psychological or psychosocial interventions to prevent relapse or recurrence in
      patients with depression. As the broader definition of 'low-intensity'
      psychological intervention is somewhat contested, the review was conducted in two
      parts: A, a systematic review of all evaluations of 'low-intensity' interventions
      that were delivered by para-professionals, peer supporters or psychological well
      being practitioners as defined by the Improving Access to Psychological Therapies
      programme; and B, a scoping review of relevant evaluations of interventions
      involving qualified mental health professionals (e.g. psychiatrists, clinical
      psychologists, cognitive behavioural therapists) involving < 6 hours of contact
      per patient. DATA SOURCES: Comprehensive literature searches were developed;
      electronic databases were searched from inception until September 2010 (including
      MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, EMBASE, The
      Cochrane Library), internet resources were used to identify guidelines on the
      treatment of depression, and the bibliographies of relevant reviews, guidelines
      and included studies were scrutinised. REVIEW METHODS: Two reviewers
      independently screened titles and abstracts; data were extracted independently by
      one reviewer using a standardised data extraction form and checked by another.
      Discrepancies were resolved by consensus, with involvement of a third reviewer
      when necessary. The inclusion criteria were population - adults or adolescents
      who had received treatment for depression; intervention - part A, low-intensity
      interventions, specifically any unsupported psychological/psychosocial
      interventions or any supported interventions that did not involve highly
      qualified mental health professionals, and, part B, interventions carried out by
      qualified mental health professionals that involved < 6 hours of contact per
      patient; comparator - any, including no treatment, placebo, psychological or
      pharmacological interventions; outcomes - relapse or recurrence, other outcomes
      (e.g. social function, quality of life) were recorded where reported; and study
      design - for clinical effectiveness, randomised, quasi-randomised and non
      randomised studies with concurrent control patients. For cost-effectiveness, full
      economic evaluations that compared two or more treatment options and considered
      both costs and consequences. No studies met the main part A inclusion criteria.
      RESULTS: For the clinical effectiveness review, 17 studies (14 completed, three
      ongoing), reported in 27 publications, met the part B inclusion criteria. These
      studies were clinically and methodologically diverse, and reported differing
      degrees of efficacy for the evaluated interventions. One randomised controlled
      trial (RCT), which evaluated a collaborative care-type programme, was potentially
      relevant to part A; this study reported no difference between patients receiving
      the intervention and those receiving usual care in terms of relapse of depression
      over 12 months. For the cost-effectiveness review, two studies met the criteria
      for part B. One of these was an economic evaluation of the RCT above, which was
      potentially relevant to part A. This evaluation found that the intervention may
      be a cost-effective use of resources when compared with usual care; however, it
      was unclear how valid these estimates were for the NHS. LIMITATIONS: Although any
      definition of 'brief' is likely to be somewhat arbitrary, an inclusion threshold
      of 6 hours contact per patient was used to select brief high-intensity
      intervention studies. Most excluded studies evaluated clearly resource-intensive
      interventions, though occasionally, studies were excluded on the basis of having
      only slightly more than 6 hours contact per patient. CONCLUSIONS: There is
      inadequate evidence to determine the clinical effectiveness or cost-effectiveness
      of low-intensity interventions for the prevention of relapse or recurrence of
      depression. A scoping review of brief high-intensity therapies indicates that
      some approaches have shown promise in some studies, but findings have not been
      consistent. Many uncertainties remain and further primary research is required.
      Careful consideration should be given to the scope of such research; it is
      important to evaluate the broader patient pathway accounting for the
      heterogeneous patient groups of interest. Future RCTs conducted in a UK primary
      care setting should include adult participants in remission or recovery from
      depression, and evaluate the quality of the intervention and consistency of
      delivery across practitioners where appropriate. The occurrence of relapse or
      recurrence should be measured using established methods, and functional outcomes
      as well as symptoms should be measured; data on quality of life using a generic
      instrument, such as the European Quality of Life-5 Dimensions (EQ-5D), should be
      collected. FUNDING: The National Institute for Health Research Health Technology
      Assessment programme.

PMID- 22642792
TI  - Eleventh Conversation in the Discipline Biomolecular Stereodynamics University at
      Albany, SUNY, Albany, New York, June 15-19, 1999.

PMID- 22642790
TI  - Prevention of methamphetamine-induced microglial cell death by TNF-alpha and IL-6
      through activation of the JAK-STAT pathway.
AB  - BACKGROUND: It is well known that methamphetamine (METH) is neurotoxic and recent
      studies have suggested the involvement of neuroinflammatory processes in brain
      dysfunction induced by misuse of this drug. Indeed, glial cells seem to be
      activated in response to METH, but its effects on microglial cells are not fully
      understood. Moreover, it has been shown that cytokines, which are normally
      released by activated microglia, may have a dual role in response to brain
      injury. This led us to study the toxic effect of METH on microglial cells by
      looking to cell death and alterations of tumor necrosis factor-alpha (TNF-alpha)
      and interleukine-6 (IL-6) systems, as well as the role played by these cytokines.
      METHODS: We used the N9 microglial cell line, and cell death and proliferation
      were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling
      assay and incorporation of bromodeoxyuridine, respectively. The TNF-alpha and IL
      6 content was quantified by enzyme-linked immunosorbent assay, and changes in TNF
      receptor 1, IL-6 receptor-alpha, Bax and Bcl-2 protein levels by western
      blotting. Immunocytochemistry analysis was also performed to evaluate alterations
      in microglial morphology and in the protein expression of phospho-signal
      transducer and activator of transcription 3 (pSTAT3). RESULTS: METH induced
      microglial cell death in a concentration-dependent manner (EC50 = 1 mM), and also
      led to significant morphological changes and decreased cell proliferation.
      Additionally, this drug increased TNF-alpha extracellular and intracellular
      levels, as well as its receptor protein levels at 1 h, whereas IL-6 and its
      receptor levels were increased at 24 h post-exposure. However, the endogenous
      proinflammatory cytokines did not contribute to METH-induced microglial cell
      death. On the other hand, exogenous low concentrations of TNF-alpha or IL-6 had a
      protective effect. Interestingly, we also verified that the anti-apoptotic role
      of TNF-alpha was mediated by activation of IL-6 signaling, specifically the janus
      kinase (JAK)-STAT3 pathway, which in turn induced down-regulation of the Bax/Bcl
      2 ratio. CONCLUSIONS: These findings show that TNF-alpha and IL-6 have a
      protective role against METH-induced microglial cell death via the IL-6 receptor,
      specifically through activation of the JAK-STAT3 pathway, with consequent changes
      in pro- and anti-apoptotic proteins.

PMID- 22642793
TI  - FK1706, a novel non-immunosuppressive immunophilin ligand, modifies gene
      expression in the dorsal root ganglia during painful diabetic neuropathy.
AB  - OBJECTIVES: FK1706, a non-immunosuppressive immunophilin ligand, potentiated
      nerve growth factor-induced neurite outgrowth, putatively mediated via FKBP-52
      and the Ras/Raf/MAPK signaling pathway. It also improved mechanical allodynia
      accompanied by the recovery of intraepidermal nerve fiber density in a painful
      diabetic neuropathy in rats. The aim of this study was to demonstrate the gene
      expression profiling in dorsal root ganglion in streptozotocin-induced diabetic
      rats related to pain and anti-allodynia effects of FK1706 administration to
      elucidate the putative mechanisms of its neurotrophic activity in vivo. Here, we
      analyzed gene expression of the dorsal root ganglia using microarray together
      with behavioral measurement of mechanical allodynia in diabetic rats to try to
      capture the global fingerprint of changes in gene expression associated with
      FK1706 administration. METHODS: The withdrawal threshold of streptozotocin
      induced diabetic rats was measured by an electronic von Frey system. The gene
      expression of the ganglia from L4 to L6 obtained from streptozotocin-treated rats
      with or without chronic administration of FK1706 was analyzed using an Affymetrix
      GeneChip to extract interesting genes in the development of mechanical allodynia
      in diabetes and anti-allodynia effect of FK1706. RESULTS: Daily oral
      administration of FK1706 improved mechanical allodynia without decreasing plasma
      glucose levels. From gene expression analysis, the expression of thioredoxin
      interacting protein gene was sustained to increased change, whereas those of
      collagen I alpha1, II alpha1 and IX alpha1 genes were decreased from 2 to 4 weeks
      after streptozotocin injection. While no changes occurred after 1 week of
      commencing of FK1706 administration (2 weeks after streptozotocin injection),
      changes in expression more than 1.5-fold were observed for genes such as Ckm,
      Actn3, Atp2a1, Bglap, Acta1, Myl1, Tnnc2, and Mylpf at 2 weeks of FK1706
      administration (3 weeks after streptozotocin injection). The genes RGD1564519,
      Hbb, LOC689064, Arpc4 and S100a9 were upregulated in comparison with
      streptozotocin-injected control group at 3 weeks of FK1706 administration; on the
      other hand, those of Actn3, Atp2a1 were downregulated by FK1706. DISCUSSION:
      FK1706 ameliorates mechanical allodynia with accompanying increases in gene
      expressions possibly related to neurite outgrowth, development, differentiation,
      and nociceptive sensitivity.

PMID- 22642794
TI  - Comparison of the WST-8 colorimetric method and the CLSI broth microdilution
      method for susceptibility testing against drug-resistant bacteria.
AB  - The minimum inhibitory concentrations (MICs) obtained from the susceptibility
      testing of various bacteria to antibiotics were determined by a colorimetric
      microbial viability assay based on reduction of a tetrazolium salt {2-(2-methoxy
      4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium
      salt (WST-8)} via 2-methyl-1,4-napthoquinone as an electron mediator and compared
      with those obtained by the broth microdilution methods approved by the Clinical
      and Laboratory Standard Institute (CLSI). Especially for drug-resistant bacteria,
      the CLSI method at an incubation time of 24h tended to give lower MICs. The
      extension of incubation time was necessary to obtain consistent MICs for drug
      resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA),
      vancomycin-resistant enterococi (VRE) and multi-drug resistant Pseudomonas
      aeruginosa (MDRP) in the broth microdilution method. There was excellent
      agreement between the MICs determined after 24h using the WST-8 colorimetric
      method and those obtained after 48-96 h using the broth microdilution method. The
      results suggest that the WST-8 colorimetric assay is a useful method for rapid
      determination of consistent MICs for drug-resistant bacteria.

PMID- 22642795
TI  - Differentiating between trivalent lanthanides and actinides.
AB  - The reactions of LnCl(3) with molten boric acid result in the formation of
      Ln[B(4)O(6)(OH)(2)Cl] (Ln = La-Nd), Ln(4)[B(18)O(25)(OH)(13)Cl(3)] (Ln = Sm, Eu),
      or Ln[B(6)O(9)(OH)(3)] (Ln = Y, Eu-Lu). The reactions of AnCl(3) (An = Pu, Am,
      Cm) with molten boric acid under the same conditions yield Pu[B(4)O(6)(OH)(2)Cl]
      and Pu(2)[B(13)O(19)(OH)(5)Cl(2)(H(2)O)(3)], Am[B(9)O(13)(OH)(4)].H(2)O, or
      Cm(2)[B(14)O(20)(OH)(7)(H(2)O)(2)Cl]. These compounds possess three-dimensional
      network structures where rare earth borate layers are joined together by BO(3)
      and/or BO(4) groups. There is a shift from 10-coordinate Ln(3+) and An(3+)
      cations with capped triangular cupola geometries for the early members of both
      series to 9-coordinate hula-hoop geometries for the later elements. Cm(3+) is
      anomalous in that it contains both 9- and 10-coordinate metal ions. Despite these
      materials being synthesized under identical conditions, the two series do not
      parallel one another. Electronic structure calculations with multireference,
      CASSCF, and density functional theory (DFT) methods reveal the An 5f orbitals to
      be localized and predominately uninvolved in bonding. For the Pu(III) borates, a
      Pu 6p orbital is observed with delocalized electron density on basal oxygen atoms
      contrasting the Am(III) and Cm(III) borates, where a basal O 2p orbital
      delocalizes to the An 6d orbital. The electronic structure of the Ce(III) borate
      is similar to the Pu(III) complexes in that the Ce 4f orbital is localized and
      noninteracting, but the Ce 5p orbital shows no interaction with the coordinating
      ligands. Natural bond orbital and natural population analyses at the DFT level
      illustrate distinctive larger Pu 5f atomic occupancy relative to Am and Cm 5f, as
      well as unique involvement and occupancy of the An 6d orbitals.

PMID- 22642796
TI  - Social service offices as a point of entry into substance abuse treatment for
      poor South Africans.
AB  - BACKGROUND: In South Africa, district social service offices are often the first
      point of entry into the substance abuse treatment system. Despite this, little is
      known about the profile of people presenting with substance-related problems at
      these service points. This has a negative impact on treatment service planning.
      This paper begins to redress this gap through describing patterns of substance
      use and service needs among people using general social services in the Western
      Cape and comparing findings against the profile of persons attending specialist
      substance abuse treatment facilities in the region. METHODS: As part of a
      standard client information system, an electronic questionnaire was completed for
      each person seeking social assistance. Data on socio-demographic characteristics,
      the range of presenting problems, patterns of substance use, perceived
      consequences of substance use, as well as types of services provided were
      analysed for the 691 social welfare clients who reported substance use between
      2007 and 2009. These data were compared against clients attending substance abuse
      treatment centres during the same time period. RESULTS: Findings indicate that
      social services offices are used as a way of accessing specialist services but
      are also used as a service point, especially by groups under-represented in the
      specialist treatment sector. Women, people from rural communities and people with
      alcohol-related problems are more likely to seek assistance at social service
      offices providing low threshold intervention services than from the specialist
      treatment sector. CONCLUSIONS: The study provides evidence that social services
      are a point of entry and intervention for people from underserved communities in
      the Western Cape. If these low-threshold services can be supported to provide
      good quality services, they may be an effective and efficient way of improving
      access to treatment in a context of limited service availability.

PMID- 22642797
TI  - Chronic non-granulomatous supraglottitis: a rare and difficult disease.
AB  - OBJECTIVES: To examine chronic non-granulomatous supraglottitis, a rare disorder
      of uncertain aetiology with few reported cases in the literature. CASE REPORTS:
      We describe two cases of chronic non-granulomatous supraglottitis that led to
      persistent respiratory compromise. Patients underwent extensive investigation
      that failed to reveal a definitive diagnosis. CONCLUSION: In patients suffering
      from chronic inflammation of the supraglottic larynx without evidence of
      infection, neoplasm or granulomatous disease, many disorders must be ruled out in
      order to diagnose chronic non-granulomatous supraglottitis, which is a diagnosis
      of exclusion. We review the literature on this rare entity, discuss current
      management strategies, and suggest an algorithm for diagnostic investigation.

PMID- 22642798
TI  - Peak longitudinal strain most accurately reflects myocardial segmental viability
      following acute myocardial infarction - an experimental study in open-chest pigs.
AB  - BACKGROUND: The extension and the transmurality of the myocardial infarction are
      of high predictive value for clinical outcome. The aim of the study was to
      characterize the ability of longitudinal, circumferential and radial strain
      measured by 2-dimensional speckle tracking echocardiography (2D-STE) to predict
      the extent of necrosis in myocardial segments following acute myocardial
      infarction and to separate transmural necrotic segments from non-transmural
      necrotic segments in a full 18-segment porcine model. METHODS: 2D-STE strain was
      assessed in long- and short-axis following myocardial infarction in ten open
      chest anesthetized pigs. Strain was defined according to systolic peak values. In
      segments displaying both negative and positive peaks, only the peak with the
      highest absolute value was utilized. Necrosis was measured by 2,3,5
      triphenyltetrazolium chloride (TTC) staining and expressed as percent of each
      myocardial segment. RESULTS: Significant correlations were found between the
      extension of necrosis and all measured parameters of myocardial deformation (p <
      0.001), but was stronger for longitudinal strain (r(2) = 0.52) than
      circumferential strain (r(2) = 0.38) and radial strain (r(2) = 0.23). The area
      under the receiver operator characteristic curve (AUC) for separating transmural
      necrotic segments (>50% necrosis) from predominantly viable segments (0-50%
      necrosis) was significantly larger for longitudinal strain (AUC = 0.98, CI = 0.97
      1.00) when compared with circumferential strain (AUC = 0.91, CI = 0.84-0.97, p <
      0.05) and radial strain (AUC = 0.90, CI = 0.83 - 0.96, p < 0.01), indicating a
      stronger ability of longitudinal strain to identify segments with transmural
      necrosis. CONCLUSION: Peak strain values derived from 2D-STE correlate well with
      the extent of necrosis in myocardial segments following acute myocardial
      infarction. Longitudinal strain most accurately reflects myocardial segmental
      viability in this setting.

PMID- 22642799
TI  - First-line disease-modifying therapies in paediatric multiple sclerosis: a
      comprehensive overview.
AB  - Paediatric multiple sclerosis (MS) is defined as the onset of MS before the age
      of 18 years. Immunomodulatory disease-modifying therapies (i.e. the interferons
      [IFNs] and glatiramer acetate) are considered first-line treatments in adult
      patients with MS, but they are largely understudied in the paediatric population.
      IFNbeta is a type 1 IFN produced by fibroblasts. The therapeutic effect achieved
      by IFNbeta in MS is believed to be the result of a variety of mechanisms,
      including the inhibition of T-cell proliferation and a shift in cytokine
      production. There are currently two forms of recombinant IFNbeta used
      therapeutically for MS: IFNbeta-1a and IFNbeta-1b. Two formulations of IFNbeta-1a
      exist, one administered as an intramuscular injection once weekly and the other
      by subcutaneous injection three times per week. Only one type of IFNbeta-1b
      product is on the market, a subcutaneous injection administered every other day.
      Pharmacokinetic studies of these agents in children do not exist and available
      data are primarily from studies in healthy adults. It does not appear that the
      various formulations differ significantly in terms of bioavailability or efficacy
      in adults. The toxicity profiles of the interferon formulations are similar, with
      the most common adverse effects in children including flu-like symptoms,
      injection site reactions and transient elevations in liver enzymes. Glatiramer
      acetate is a mixture of synthetic polypeptide chains consisting of four different
      amino acids. Glatiramer acetate appears to mimic the antigenic properties of
      myelin basic protein (MBP), and by doing so, alters T-cell activation in the
      periphery. Glatiramer acetate is administered as a once-daily subcutaneous
      injection. Similar to the IFNbeta formulations, there are no pharmacokinetic
      studies of this agent in children. The most common adverse effects include
      injection site reactions and transient chest tightness. Fingolimod, a sphingosine
      1-phosphate receptor modulator, is a new disease-modifying therapy that was
      approved by the US FDA in 2010 for the first-line treatment of relapsing forms of
      MS in adults. However, due to a lack of information and clinical data on this
      agent in the paediatric population, it is not included in this discussion. Dose
      finding studies of the IFNs and glatiramer acetate in the paediatric population
      are limited. Dosing recommendations are largely based on tolerability studies,
      with most children and adolescents tolerating the full adult doses. Clinical
      studies of IFNs in children have not been objectively designed to establish the
      efficacy of these therapies, and evidence is limited to that of observational
      trials and retrospective case reports. However, the largest cohort (130 cases) of
      paediatric MS patients studied to date reported a reduction in annual relapse
      rate with all three of the different IFNbeta formulations and glatiramer acetate
      after a follow-up period of more than 4 years. Treatment with one of the first
      line agents should be offered to any patient after the occurrence of a second
      demyelinating episode. The efficacy of the four first-line disease-modifying
      agents is considered to be relatively equivalent, and the choice of agent should
      be determined on an individual patient basis, taking into account potential
      adverse effects and patient preferences. Current data suggest that the IFNs and
      glatiramer acetate are safe and effective therapies in paediatric patients with
      MS. However, further studies evaluating the pharmacokinetics, appropriate dosing
      and comparisons of efficacy among these agents are needed to determine the most
      appropriate and evidence-based treatment decisions in this population.

PMID- 22642800
TI  - Efficacy of an improved absorbent pad on incontinence-associated dermatitis in
      older women: cluster randomized controlled trial.
AB  - BACKGROUND: Most older adults with urinary incontinence use absorbent pads.
      Because of exposure to moisture and chemical irritating substances in urine, the
      perineal skin region is always at risk for development of incontinence-associated
      dermatitis (IAD). The aim of this study was to examine the efficacy of an
      improved absorbent pad against IAD. METHODS: A cluster randomized controlled
      design was used to compare the efficacy of two absorbent pads. Female inpatients
      aged >=65 years who had IAD and used an absorbent pad or diaper all day were
      enrolled. Healing rate of IAD and variables of skin barrier function such as skin
      pH and skin moisture were compared between the usual absorbent pad group (n = 30)
      and the test absorbent pad group (n = 30). RESULTS: Thirteen patients (43.3%)
      from the test absorbent pad group and 4 patients (13.3%) from the usual absorbent
      pad group recovered completely from IAD. Moreover, the test absorbent pad group
      healed significantly faster than the usual absorbent pad group (p = 0.009). On
      the other hand, there were no significant differences between the two groups in
      skin barrier function. CONCLUSION: The test absorbent pad for older adults with
      urinary incontinence might be more efficacious against IAD than usual absorbent
      pad. TRIAL REGISTRATION: UMIN-CTR: UMIN000006188.

PMID- 22642801
TI  - Potential function of added minerals as nucleation sites and effect of humic
      substances on mineral formation by the nitrate-reducing Fe(II)-oxidizer
      Acidovorax sp. BoFeN1.
AB  - The mobility of toxic metals and the transformation of organic pollutants in the
      environment are influenced and in many cases even controlled by iron minerals.
      Therefore knowing the factors influencing iron mineral formation and
      transformation by Fe(II)-oxidizing and Fe(III)-reducing bacteria is crucial for
      understanding the fate of contaminants and for the development of remediation
      technologies. In this study we followed mineral formation by the nitrate-reducing
      Fe(II)-oxidizing strain Acidovorax sp. BoFeN1 in the presence of the crystalline
      Fe(III) (oxyhydr)oxides goethite, magnetite and hematite added as potential
      nucleation sites. Mossbauer spectroscopy analysis of minerals precipitated by
      BoFeN1 in (57)Fe(II)-spiked microbial growth medium showed that goethite was
      formed in the absence of mineral additions as well as in the presence of goethite
      or hematite. The presence of magnetite minerals during Fe(II) oxidation induced
      the formation of magnetite in addition to goethite, while the addition of humic
      substances along with magnetite also led to goethite but no magnetite. This study
      showed that mineral formation not only depends on the aqueous geochemical
      conditions but can also be affected by the presence of mineral nucleation sites
      that initiate precipitation of the same underlying mineral phases.

PMID- 22642803
TI  - Pharmacokinetics and metabolism of midazolam in chimeric mice with humanised
      livers.
AB  - The pharmacokinetics and biotransformation of midazolam were investigated
      following single oral doses of 0.1, 1 and 10 mg/kg to chimeric mice with
      humanised livers (PXB mice) and to severe combined immunodeficient (SCID) mice
      used as controls. Pharmacokinetic analysis, on whole blood, revealed rapid
      absorption of the administered midazolam with a higher C(max) in PXB compared to
      SCID. The exposure to 1'-hydroxymidazolam was approximately 14-fold greater than
      to midazolam in the SCID mice and close to equivalent in the PXB mice. The
      metabolism of midazolam in SCID mice was faster than in the PXB mice such that
      pharmacokinetic data for midazolam in SCID mice could not be generated from the
      lowest dose in these animals. Both oxidative and conjugative metabolic pathways
      were identified in the PXB mice. All the major circulating metabolites observed
      in humans; 1'-hydroxymidazolam, 4'-hydroxymidazolam, 1',4'-dihydroxymidazolam and
      1'-hydroxymidazolam glucuronide, were detected in the blood of PXB mice. However,
      4'-hydroxymidazolam and the 1'-hydroxymidazolam glucuronide were not detected in
      blood samples obtained from SCID mice. The midazolam metabolite profile in the
      PXB mouse was similar to that previously reported for human suggesting that the
      PXB mouse model can provide a model system for predicting circulating human
      metabolites.

PMID- 22642802
TI  - IFN-gamma protects from lethal IL-17 mediated viral encephalomyelitis independent
      of neutrophils.
AB  - BACKGROUND: The interplay between IFN-gamma, IL-17 and neutrophils during CNS
      inflammatory disease is complex due to cross-regulatory factors affecting both
      positive and negative feedback loops. These interactions have hindered the
      ability to distinguish the relative contributions of neutrophils, Th1 and Th17
      cell-derived effector molecules from secondary mediators to tissue damage and
      morbidity. METHODS: Encephalitis induced by a gliatropic murine coronavirus was
      used as a model to assess the direct contributions of neutrophils, IFN-gamma and
      IL-17 to virus-induced mortality. CNS inflammatory conditions were selectively
      manipulated by adoptive transfer of virus-primed wild-type (WT) or IFN-gamma
      deficient (GKO) memory CD4+ T cells into infected SCID mice, coupled with
      antibody-mediated neutrophil depletion and cytokine blockade. RESULTS: Transfer
      of GKO memory CD4+ T cells into infected SCID mice induced rapid mortality
      compared to recipients of WT memory CD4+ T cells, despite similar virus control
      and demyelination. In contrast to recipients of WT CD4+ T cells, extensive
      neutrophil infiltration and IL-17 expression within the CNS in recipients of GKO
      CD4+ T cells provided a model to directly assess their contribution(s) to
      disease. Recipients of WT CD4+ T cells depleted of IFN-gamma did not express IL
      17 and were spared from mortality despite abundant CNS neutrophil infiltration,
      indicating that mortality was not mediated by excessive CNS neutrophil
      accumulation. By contrast, IL-17 depletion rescued recipients of GKO CD4+ T cells
      from rapid mortality without diminishing neutrophils or reducing GM-CSF,
      associated with pathogenic Th17 cells in CNS autoimmune models. Furthermore, co
      transfer of WT and GKO CD4+ T cells prolonged survival in an IFN-gamma dependent
      manner, although IL-17 transcription was not reduced. CONCLUSIONS: These data
      demonstrate that IL-17 mediates detrimental clinical consequences in an IFN-gamma
      deprived environment, independent of extensive neutrophil accumulation or GM-CSF
      upregulation. The results also suggest that IFN-gamma overrides the detrimental
      IL-17 effector responses via a mechanism downstream of transcriptional
      regulation.

PMID- 22642804
TI  - Pharmacokinetics, oral bioavailability and metabolism of a novel isoquinolinone
      based melatonin receptor agonist in rats.
AB  - 7-Methoxy-6-(3-methoxy-benzyloxy)-2-methylisoquinolin-1(2H)-one (named as IS0042)
      is a newly identified melatoninergic agonist which exhibits selectivity to the
      type 2 melatonin receptor. Here, we examined the in vitro and in vivo
      pharmacokinetics properties of IS0042 in rats. IS0042 was considerably lipophilic
      with a modest aqueous solubility of 27.3 ug/mL. It was stable in simulated
      gastrointestinal fluid, and readily penetrated across differentiated Caco-2 cell
      model of intestinal barrier, suggesting good oral absorption. IS0042 underwent
      metabolism in rat intestinal and liver microsomes with an in vitro half-life of
      367.5 +/- 36.6 and 17.5 +/- 2.7 min, respectively. Metabolite identification
      suggested that the major biotransformation pathways included the cleavage of
      ether bond, hydroxylation and demethylation. The same metabolites were also
      present in blood circulation following oral administration, indicating a good
      correlation between in vitro and in vivo metabolism. The pharmacokinetics
      parameters of IS0042 were evaluated after intravenous administration (10 or 25
      mg/kg) and oral administration (100 mg/kg) of the drug to rats. IS0042 showed
      moderate clearance (0.73-1.02 L/h/kg), large volume of distribution (1.76-3.16
      L/kg) and long elimination half-life (3.11-6.04 h) after intravenous
      administration. The absolute oral bioavailability of IS0042 was relatively low
      (9.8-18.6%). Overall, these results provide important parameters for the further
      development of this novel class of melatoninergic ligands.

PMID- 22642805
TI  - Highly diastereo- and enantioselective Cu-catalyzed [3 + 3] cycloaddition of
      propargyl esters with cyclic enamines toward chiral bicyclo[n.3.1] frameworks.
AB  - A new Cu-catalyzed asymmetric [3 + 3] cycloaddition of propargyl esters with
      cyclic enamines is reported. With a combination of Cu(OAc)(2).H(2)O and a chiral
      tridentate ferrocenyl-P,N,N ligand as the catalyst, perfect endo selectivities
      (endo/exo > 98/2) and excellent enantioselectivities (up to 98% ee) for endo
      cycloadducts were achieved under mild conditions. This method provides a simple
      and efficient approach for the synthesis of optically active bicyclo[n.3.1]
      frameworks.

PMID- 22642806
TI  - Invariants and other structural properties of biochemical models as a constraint
      satisfaction problem.
AB  - BACKGROUND: We present a way to compute the minimal semi-positive invariants of a
      Petri net representing a biological reaction system, as resolution of a
      Constraint Satisfaction Problem. The use of Petri nets to manipulate Systems
      Biology models and make available a variety of tools is quite old, and recently
      analyses based on invariant computation for biological models have become more
      and more frequent, for instance in the context of module decomposition. RESULTS:
      In our case, this analysis brings both qualitative and quantitative information
      on the models, in the form of conservation laws, consistency checking, etc.
      thanks to finite domain constraint programming. It is noticeable that some of the
      most recent optimizations of standard invariant computation techniques in Petri
      nets correspond to well-known techniques in constraint solving, like symmetry
      breaking. Moreover, we show that the simple and natural encoding proposed is not
      only efficient but also flexible enough to encompass sub/sur-invariants,
      siphons/traps, etc., i.e., other Petri net structural properties that lead to
      supplementary insight on the dynamics of the biochemical system under study.
      CONCLUSIONS: A simple implementation based on GNU-Prolog's finite domain solver,
      and including symmetry detection and breaking, was incorporated into the BIOCHAM
      modelling environment and in the independent tool Nicotine. Some illustrative
      examples and benchmarks are provided.

PMID- 22642807
TI  - Recurrent phosphaturic mesenchymal tumour of the temporal bone causing deafness
      and facial nerve palsy.
AB  - OBJECTIVE: We describe the first reported case of a phosphaturic mesenchymal
      tumour, mixed connective tissue variant, invading the temporal bone. CASE REPORT:
      A female patient presented with increasing deafness. On examination there
      appeared to be a mass behind an intact tympanic membrane. Further radiological
      investigation showed a vascular mass occupying the middle ear, mastoid and
      internal auditory meatus. This was surgically resected and revealed to be a
      benign phosphaturic mesenchymal tumour, mixed connective tissue variant. The
      tumour recurred a year later, presenting as facial nerve palsy. A revision
      procedure was carried out; the tumour was excised with the sacrifice of a segment
      of the facial nerve, and a facial-hypoglossal nerve anastomosis was performed.
      CONCLUSION: This case report highlights the occurrence of this benign but
      sometimes aggressive tumour, of which both clinicians and pathologists should be
      aware. Early recognition of the condition remains of utmost importance to
      minimise the debilitating consequences of long-term osteomalacia in affected
      patients, and to prevent extracranial and intracranial complications caused by
      the tumour.

PMID- 22642808
TI  - Using experimental autoimmune encephalomyelitis as a model to study the effect of
      prenatal stress on fetal programming.
AB  - OBJECTIVES: There is a growing evidence to suggest that the antecedents of some
      adult diseases can be traced back to their fetal origins. Despite extensive
      research on such diseases, to our knowledge, there has been no research
      investigating the relationship between the origins  of multiple sclerosis (MS)
      disease and maternal infections. The aim of this study was to examine the role of
      prenatal exposure to endotoxin in fetal programming with respect to induction of
      susceptibility/vulnerability to MS. METHODS: The pregnant dams were administered
      a single  intraperitoneal injection of lipopolysaccharide in gestational day 10.
      The male offspring were weighed and examined for clinical signs of experimental
      autoimmune encephalomyelitis in a blinded fashion within 36 days after
      immunization (postnatal day 63-98). RESULTS: Our data  provide the evidence
      showing prenatal exposures to higher doses of Lipopolysaccharide resulted in an
      earlier onset of the disease, an augmentation of its clinical signs, and lower
      body weight in the prenatally Lipopolysaccharide -treated C57BL/6 mice after the
      immunization. DISCUSSION: Therefore, the present research can provide evidence
      that prenatal stress may play a role in enhancing the clinical symptoms of
      experimental autoimmune encephalomyelitis/MS.

PMID- 22642809
TI  - Complement regulatory protein Crry deficiency contributes to the antigen specific
      recall response in experimental autoimmune myasthenia gravis.
AB  - BACKGROUND: Myasthenia gravis (MG) and animal model of experimental autoimmune
      myasthenia gravis (EAMG) is the most common autoimmune disorder of neuromuscular
      transmission. The disease is caused by the breakdown of the acetylcholine
      receptor (AChR) which is largely due to complement activation at the
      neuromuscular junction (NMJ). Limited knowledge exists to the extent that
      complement receptor 1-related gene/protein y deficiency (Crry -/-) modulates the
      adaptive immune response and EAMG outcome. METHODS: Mouse EAMG was induced by
      s.c. administrations of purified acetylcholine receptor (AChR) to Crry -/- and
      age- matched WT (C57BL/6) mice. Disease severity was assessed by clinical score
      assessment and muscle grip strength measurements. Serum complement activity was
      determined by hemolytic assay. ELISA was used to detect the level of AChR
      specific antibodies. Splenic cells were analyzed for T and B cells subsets
      distribution, release of cytokines and AChR specific recall responses. Deposition
      of complement components at the NMJ was assessed by immunofluorescence staining.
      RESULTS: In comparison to WT EAMG, Crry -/- EAMG mice showed signs of augmented
      muscle weakness but differences, except for one time point, were not
      statistically significant. Serum complement activity was reduced in Crry -/- EAMG
      mice and no substantial changes in deposition of C3, C3b/iC3b and C5b-9 (MAC) at
      the NMJ between WT EAMG and Crry -/- EAMG mice were detected. Lack of Crry
      affected adaptive immune response. Crry -/- EAMG mice showed increases in the
      number of AChR specific splenic T-cells secreting IFN-gamma and IL-4. Production
      of complement fixing antibodies (IgG2b, IgG2c) was also augmented. More Th1, Th2
      and Th17 cytokines were released into the bloodstream of Crry -/- EAMG mice.
      CONCLUSIONS: Data suggest that Crry deficiency modulates the adaptive immune
      response in EAMG, but its effect on disease outcome is limited. This was due to
      the generally lower serum complement level caused by increased C3 turnover.
      Modulation of complement activity with soluble or membrane bound regulators of
      complement activity represents a potentially effective approach to modify
      autoimmune processes in MG and EAMG.

PMID- 22642810
TI  - Structure of MMACHC reveals an arginine-rich pocket and a domain-swapped dimer
      for its B12 processing function.
AB  - Defects in the MMACHC gene represent the most common disorder of cobalamin (Cbl)
      metabolism, affecting synthesis of the enzyme cofactors adenosyl-Cbl and methyl
      Cbl. The encoded MMACHC protein binds intracellular Cbl derivatives with
      different upper axial ligands and exhibits flavin mononucleotide (FMN)-dependent
      decyanase activity toward cyano-Cbl as well as glutathione (GSH)-dependent
      dealkylase activity toward alkyl-Cbls. We determined the structure of human
      MMACHC.adenosyl-Cbl complex, revealing a tailor-made nitroreductase scaffold
      which binds adenosyl-Cbl in a "base-off, five-coordinate" configuration for
      catalysis. We further identified an arginine-rich pocket close to the Cbl binding
      site responsible for GSH binding and dealkylation activity. Mutation of these
      highly conserved arginines, including a replication of the prevalent MMACHC
      missense mutation, Arg161Gln, disrupts GSH binding and dealkylation. We further
      showed that two Cbl-binding monomers dimerize to mediate the reciprocal exchange
      of a conserved "PNRRP" loop from both subunits, serving as a protein cap for the
      upper axial ligand in trans and required for proper dealkylation activity. Our
      dimeric structure is supported by solution studies, where dimerization is
      triggered upon binding its substrate adenosyl-Cbl or cofactor FMN. Together our
      data provide a structural framework to understanding catalytic function and
      disease mechanism for this multifunctional enzyme.

PMID- 22642811
TI  - Chandipura virus infection in mice: the role of toll like receptor 4 in
      pathogenesis.
AB  - BACKGROUND: The susceptibility of mice and humans to Chandipura virus infection
      is age-dependent. Upon experimental infection, mice secrete significant amounts
      of proinflammatory cytokines. Similarly, children who recover from natural
      infection with the virus show significant amounts of TNF-alpha production,
      suggesting that innate immunity plays a major role in the response to Chandipura
      virus. Toll-like receptors (TLR) are key host molecules involved in innate immune
      responses in infections. Therefore, the aim of this study was to examine the role
      of TLR in the response to Chandipura virus infection. METHODS: The mouse monocyte
      macrophage cell line, RAW 264.7, and C3H/HeJ mice were used as models. Micro
      array techniques were used to identify the type of TLR involved in the response
      to infection. The results were validated by examining TLR expression using flow
      cytometry and by measuring the levels of proinflammatory cytokines and nitric
      oxide (NO) in the culture supernatants using bead assays and the Griess method,
      respectively. The pathogenic role of Toll-like receptor 4 (TLR4) was studied in a
      TLR4 mutant strain of mice -C3H/HeJ and the results compared with those from wild
      type mice- C3H/CaJ. The pathogenic effects of NO were studied by treating
      experimentally infected mice with the NO inhibitor, aminoguanidine (AG). RESULTS:
      The micro array results showed that TLR4 was regulated after Chandipura virus
      infection. At high multiplicities of infection (10 MOI), RAW cells up- regulated
      cell surface expression of TLR4 and secreted significant amounts of TNF-alpha,
      MCP-1, IL-10 and IL-12 and NO. The survival rate of C3H/HeJ mice was higher than
      those of wild-type C3H/CaJ mice. The survived C3H/HeJ mice secreted significant
      quantity of MCP-1 and IFN-gamma cytokines and cleared virus from brain.
      Similarly, the survival rate of AG-treated mice was higher than those of the
      untreated controls. CONCLUSIONS: Chandipura virus regulates TLR4, which leads to
      the secretion of proinflammatory cytokines and NO by infected RAW cells.
      Difference in survival rate in TLR4 mutant mice and nitric oxide inhibitor
      treated mice, confirmed the role of these molecules in disease pathogenesis. The
      result is significant in clinical management and designing antiviral intervention
      for Chandipura virus infection.

PMID- 22642814
TI  - Impact of family history of gastric cancer on colorectal neoplasias in young
      Japanese.
AB  - AIM: The aim of this study was to elucidate risk factors for the development of
      colorectal neoplasia in the young population. In particular, we focused on the
      family history of gastric cancer. METHOD: Young Japanese subjects aged 30-49
      years old who underwent colonoscopy for the first time from August 2007 to August
      2008 were included in this study. A total of 300 unselected consecutive patients
      (mean age 40.5 years) were eligible for analysis, and family history of
      colorectal cancer and gastric cancer, sex, age, body mass index, positivity of
      faecal occult blood test and the presence of symptoms were evaluated. Risk
      factors for developing colorectal adenoma and/or carcinoma were assessed.
      RESULTS: Colorectal neoplasias were detected in 83 (27.7%) cases. Two were found
      to have invasive carcinoma. Univariate and multivariate analyses revealed that
      family history of gastric cancer (OR 2.09, 95% CI 1.12-3.92, P = 0.02) was an
      independent risk factor for the development of colorectal neoplasia, as well as
      male sex (OR 1.89, 95% CI 1.10-3.27, P = 0.02), older age (OR 2.05, 95% CI 1.18
      3.55, P = 0.01) and positive faecal occult blood test (OR 1.99, 95% CI 1.14-3.48,
      P = 0.02). CONCLUSION: In the young population under 50 years of age, a family
      history of gastric cancer is an independent risk factor for the development of
      colorectal neoplasia.

PMID- 22642813
TI  - Cost considerations of therapeutic options for children with asthma.
AB  - Asthma is a prevalent health condition in children, with economic implications
      for the individual and their family, as well as for societies with nationalized
      healthcare. Pharmaceutical cost is the main driver of healthcare expenditure in
      asthma. Existent explicit guidelines are meant to guide asthma management across
      all age groups, but they are failing. Pharmacologic management of asthma consists
      of a stepwise treatment approach to achieve symptom control. Various studies
      suggest a significant number of medical practitioners are prescribing inhaled
      corticosteroids (ICS) and ICS/long-acting beta agonist (LABA) combination
      inhalers inappropriately, including prescribing high doses of ICS without
      specialist consultation. ICS/LABA combination inhalers should only be used in
      persistent asthmatics, which account for approximately 5% of all children with
      asthma. Despite this, there is an increase in prescribing rates of ICS/LABA
      combination inhalers in the context of a decrease in the prevalence of asthma.
      Furthermore, there is inappropriate prescribing of ICS/LABA combination inhalers
      in children under 5 years of age, and initiation of relatively more expensive
      ICS/LABA combination inhalers in patients who have not previously been prescribed
      ICS. There is evidence to suggest that cost is a significant barrier to asthma
      management, especially for the more expensive ICS/LABA combination inhalers.
      Hence, prescribing cost-effective asthma medications appropriately is one of the
      most important strategies in reducing the morbidity and mortality associated with
      asthma. It is incumbent on every medical practitioner to not prescribe expensive
      medications if not indicated, both for the sake of the patient and for society.

PMID- 22642812
TI  - Effects of human intravenous immunoglobulin on amyloid pathology and
      neuroinflammation in a mouse model of Alzheimer's disease.
AB  - BACKGROUND: Human intravenous immunoglobulin (hIVIG) preparation is indicated for
      treating primary immunodeficiency disorders associated with impaired humoral
      immunity. hIVIG is known for its anti-inflammatory properties and a decent safety
      profile. Therefore, by virtue of its constituent natural anti-amyloid beta
      antibodies and anti-inflammatory effects, hIVIG is deemed to mediate beneficial
      effects to patients of Alzheimer's disease (AD). Here, we set out to explore the
      effects of hIVIG in a mouse model of AD. METHODS: We treated APP/PS1dE9
      transgenic and wild-type mice with weekly injections of a high hIVIG dose (1
      g/kg) or saline for 3 or 8 months. Treatment effect on brain amyloid pathology
      and microglial reactivity was assessed by ELISA, immunohistochemistry, RT-PCR,
      and confocal microscopy. RESULTS: We found no evidence for reduction in Abeta
      pathology; instead 8 months of hIVIG treatment significantly increased soluble
      levels of Abeta40 and Abeta42. In addition, we noticed a significant reduction in
      CD45 and elevation of Iba-1 markers in specific sub-populations of microglial
      cells. Long-term hIVIG treatment also resulted in significant suppression of TNF
      alpha and increase in doublecortin positive adult-born neurons in the dentate
      gyrus. CONCLUSIONS: Our data indicate limited ability of hIVIG to impact amyloid
      burden but shows changes in microglia, pro-inflammatory gene expression, and
      neurogenic effects. Immunomodulation by hIVIG may account for its beneficial
      effect in AD patients.

PMID- 22642815
TI  - Fast structure similarity searches among protein models: efficient clustering of
      protein fragments.
AB  - BACKGROUND: For many predictive applications a large number of models is
      generated and later clustered in subsets based on structure similarity. In most
      clustering algorithms an all-vs-all root mean square deviation (RMSD) comparison
      is performed. Most of the time is typically spent on comparison of non-similar
      structures. For sets with more than, say, 10,000 models this procedure is very
      time-consuming and alternative faster algorithms, restricting comparisons only to
      most similar structures would be useful. RESULTS: We exploit the inverse triangle
      inequality on the RMSD between two structures given the RMSDs with a third
      structure. The lower bound on RMSD may be used, when restricting the search of
      similarity to a reasonably low RMSD threshold value, to speed up similarity
      searches significantly. Tests are performed on large sets of decoys which are
      widely used as test cases for predictive methods, with a speed-up of up to 100
      times with respect to all-vs-all comparison depending on the set and parameters
      used. Sample applications are shown. CONCLUSIONS: The algorithm presented here
      allows fast comparison of large data sets of structures with limited memory
      requirements. As an example of application we present clustering of more than
      100000 fragments of length 5 from the top500H dataset into few hundred
      representative fragments. A more realistic scenario is provided by the search of
      similarity within the very large decoy sets used for the tests. Other
      applications regard filtering nearly-indentical conformation in selected CASP9
      datasets and clustering molecular dynamics snapshots. AVAILABILITY: A linux
      executable and a Perl script with examples are given in the supplementary
      material (Additional file 1). The source code is available upon request from the
      authors.

PMID- 22642816
TI  - Source contributions of sulfate aerosol over East Asia estimated by CMAQ-DDM.
AB  - We applied the decoupled direct method (DDM), a sensitivity analysis technique
      for computing sensitivities accurately and efficiently, to determine the source
      receptor relationships of anthropogenic SO(2) emissions to sulfate aerosol over
      East Asia. We assessed source contributions from East Asia being transported to
      Oki Island downwind from China and Korea during two air pollution episodes that
      occurred in July 2005. The contribution from China, particularly that from
      central eastern China (CEC), was found to dominate the sulfate aerosols. To study
      these contributions in more detail, CEC was divided into three regions, and the
      contributions from each region were examined. Source contributions exhibited both
      temporal and vertical variability, largely due to transport patterns imposed by
      the Asian summer monsoon. Our results are consistent with backward trajectory
      analyses. We found that anthropogenic SO(2) emissions from China produce
      significant quantities of summertime sulfate aerosols downwind of source areas.
      We used a parametric scaling method for estimating anthropogenic SO(2) emissions
      in China. Using column amounts of SO(2) derived from satellite data, and
      relationships between the column amounts of SO(2) and anthropogenic emissions,
      2009 emissions were diagnosed. The results showed that 2009 emissions of SO(2)
      from China were equivalent to 2004 levels.

PMID- 22642817
TI  - Some enzymes in marine environment: prospective applications found in patent
      literature.
AB  - Marine enzymes are characterized by well-known habitat-related features such as
      salt tolerance, hyperthermostability, barophilicity and cold adaptivity although
      the related environmental conditions are present also in many non-marine
      environments. Novel chemical and stereochemical characteristics usually possessed
      by these biocatalysts, increase their interest from scientific and applicative
      points of view both in academia and in research industry. Chemical and
      pharmaceutical fields, embracing almost the whole body of applications based on
      marine catalysts, strictly rely upon their (stereo) chemical features. This
      review article is organized in two distinct parts. In the first, examples of
      different types of enzymes identified in marine environment are tabulated showing
      the importance of marine bioprospecting: in fact, the marine habitat is one of
      the most important natural locations for enzyme bioprospecting activity. In the
      second part technological processes based on marine enzymes are described:
      remarkable or unusual bioprocesses are performed by marine biocatalysts taking
      advantages by the habitat-related characteristics above mentioned which are
      desirable features recognized from a general biotechnological perspective. With
      this aim in mind this review did not search just for novelty in most recent
      patents but for important aspects within each report, enabling the reader to
      appreciate the importance of marine environment as source of very useful
      biocatalyst.

PMID- 22642818
TI  - Patenting Penicillium strains.
AB  - Penicillium species are a widespread source of biologically active compounds and
      enzymes which are exploited in biotechnologies. The ongoing discovery of new
      species, their biochemical and molecular characterization, and the application of
      the new findings in diverse industrial processes stimulate an increasing interest
      of patentees worldwide. An overview of the patents released in the last four
      years in agriculture, bioremediation, and in several industrial fields for the
      production of biofuels, food, cosmetics and pharmaceuticals is proposed for an
      exhaustive appreciation of the potential cues offered to inventors by these
      fungi.

PMID- 22642819
TI  - Advances in zymography techniques and patents regarding protease analysis.
AB  - Detection of enzymatic activity on gel electrophoresis, namely zymography, is a
      technique that has received increasing attention in the last 10 years, according
      to the number of articles published. A growing amount of enzymes, mainly
      proteases, are now routinely detected by zymography. Detailed analytical studies
      are beginning to be published, as well as new patents have been developed. This
      new article updates the information covered in our last review, condensing the
      recent publications dealing with the identification of proteolytic enzymes in
      electrophoretic gel supports and its variations. The new advances of this method
      are basically focused towards two dimensional zymography and transfer zymography.
      Though comparatively fewer patents have been published, they basically coincide
      in the study of matrix metalloproteases. The tendency is foreseen to be very
      productive in the area of zymoproteomics, combining electrophoresis and mass
      spectrometry for the analysis of proteases.

PMID- 22642820
TI  - Recent patents in plant biotechnology: impact on global health.
AB  - Agricultural biotechnology offers a robust series of tools by which to address
      global concerns such as food security, crop protection, and fuel/energy
      requirements. A number of advances made recently in plant molecular biology also
      have resulted in applications which largely focus on improving global human
      health. This review describes some of the recent innovations in plant
      biotechnology that have come to the forefront over the past year. Included are
      novel techniques by which plants can be improved as platforms for
      biopharmaceutical protein production, a growing field also referred to as
      'molecular pharming'. The metabolic engineering of plants to produce compounds
      which have additional nutritional benefits is also outlined. The review concludes
      with a discussion of the future impact that these innovations may have both on
      global health and on the development of our future intellectual property
      landscape.

PMID- 22642821
TI  - Hairy roots, their multiple applications and recent patents.
AB  - In the last years, hairy root (HR) cultures are gaining attention in the
      biotechnology industry. This particular plant cell culture derives from explants
      infected with Agrobacterium rhizogenes. They constitute a relatively new approach
      to in vitro plant biotechnology and modern HR cultures are far away from the
      valuables findings performed by Philip R. White in the 1930's, who obtained
      indefinite growth of excised root tips. HR cultures are characterized by genetic
      and biochemical stability and high growth rate without expensive exogenous
      hormones source. HR cultures have allowed a deep study of plant metabolic
      pathways and the production of valuable secondary metabolites and enzymes, with
      therapeutic or industrial application. Furthermore, the potential of HR cultures
      is increasing continuously since different biotechnological strategies such as
      genetic engineering, elicitation and metabolic traps are currently being explored
      for discovery of new metabolites and pathways, as well as for increasing
      metabolites biosynthesis and/or secretion. Advances in design of proper
      bioreactors for HR growth are being of great interest, since scale up of
      metabolite production will allow the integration of this technology to industrial
      processes. Another application of HR cultures is related to their capabilities to
      biotransform and to degrade different xenobiotics. In this context, removal
      assays using this plant model system are useful tools for phytoremediation
      assays, previous to the application in the field. This review highlights the more
      recent application of HRs and those new patents which show their multiple
      utilities.

PMID- 22642822
TI  - Efficient method for Agrobacterium mediated transformation of Artemisia annua L.
AB  - Artemisinin, a potent antimalarial natural products isolated from aerial parts of
      Artemisia annua L. Many patents have been reported that the demand for
      artemisinin is exponentially increasing year after year due to increased
      incidences of drug resistant malaria throughout the world. Leaf explants were
      used frequently as target tissue to generate transgenic of Artemisia. annua L.
      However, obtaining a large number of transgenic lines through out the year is a
      laborious and delicate process. To circumvent this, we have developed a highly
      efficient leaf explant based Agrobacterium mediated transformation of A. annua L.
      plant. The gus gene was used as screenable marker to assess and optimize the
      performance of T-DNA delivery. The age of explant, kind of bacterial inoculation,
      suspension duration, infection times and co-culture conditions were optimized.
      The co-culture was carried out with Agrobacterium tumefaciens strain EHA105 under
      desiccation condition in the dark at 25-28 0C for 2-4 days. Complete analysis of
      transgene insertion demonstrated that the optimized method of transformation from
      leaf explants of A. annua L. was efficient and highly reproducible. 

PMID- 22642823
TI  - Clinical proteomics and OMICS clues useful in translational medicine research.
AB  - Since the advent of the new proteomics era more than a decade ago, large-scale
      studies of protein profiling have been used to identify distinctive molecular
      signatures in a wide array of biological systems, spanning areas of basic
      biological research, clinical diagnostics, and biomarker discovery directed
      toward therapeutic applications. Recent advances in protein separation and
      identification techniques have significantly improved proteomic approaches,
      leading to enhancement of the depth and breadth of proteome coverage.Proteomic
      signatures, specific for multiple diseases, including cancer and pre-invasive
      lesions, are emerging. This article combines, in a simple manner, relevant
      proteomic and OMICS clues used in the discovery and development of diagnostic and
      prognostic biomarkers that are applicable to all clinical fields, thus helping to
      improve applications of clinical proteomic strategies for translational medicine
      research.

PMID- 22642824
TI  - Structural insights into ligand dynamics: correlated oxygen and picket motion in
      oxycobalt picket fence porphyrins.
AB  - Two different oxygen-ligated cobalt porphyrins have been synthesized and the
      solid-state structures have been determined at several temperatures. The solid
      state structures provide insight into the dynamics of Co-O(2) rotation and
      correlation with protecting group disorder. [Co(TpivPP)(1-EtIm)(O(2))] (TpivPP =
      picket fence porphyrin) is prepared by oxygenation of [Co(TpivPP)(1-EtIm)(2)] in
      benzene solution. The structure at room temperature has the oxygen ligand within
      the ligand binding pocket and disordered over four sites and the trans imidazole
      is disordered over two sites. The structure at 100 K, after the crystal has been
      carefully annealed to yield a reversible phase change, is almost completely
      ordered. The phase change is reversed upon warming the crystal to 200 K,
      whereupon the oxygen ligand is again disordered but with quite unequal
      populations. Further warming to 300 K leads to greater disorder of the oxygen
      ligands with nearly equal O(2) occupancies at all four positions. The disorder of
      the tert-butyl groups of the protecting pickets is correlated with rotation of
      the O(2) around the Co-O(O(2)) bond. [Co(TpivPP)(2-MeHIm)(O(2))] is synthesized
      by a solid-state oxygenation reaction from the five-coordinate precursor
      [Co(TpivPP)(2-MeHIm)]. Exposure to 1 atm of O(2) leads to incomplete oxygenation,
      however, exposure at 5 atm yields complete oxygenation. Complete oxygenation
      leads to picket disorder whereas partial (40%) oxygenation does not.
      Crystallinity is retained on complete degassing of oxygen in the solid, and
      complete ordering of the pickets is restored. The results should provide basic
      information needed to better model M-O(2) dynamics in protein environments.

PMID- 22642826
TI  - The variation of hemodynamics relative to listening to consonance or dissonance
      during chord progression.
AB  - OBJECTIVE: The aim of the present study was to identify the variation of cerebral
      hemodynamics in relation to listening to chord progressions involving consonant
      or dissonant chords based on western music theory by near-infrared spectroscopy.
      We also tried to find out the influence  of musical education on the cortical
      hemodynamics. METHODS: Twenty subjects participated in this study. They were
      classified into two groups, namely persons with and without special musical
      training histories. We used two types of chord progressions involving consonant
      and dissonant  chords as stimuli. Then, the hemodynamics of each group was
      analyzed by optical topography to investigate the effects of each type of chord
      in the areas of left and right auditory cortices. RESULTS: In the left auditory
      cortex (superior temporal cortex), the group with higher musical  training showed
      a significant increase in oxyhemoglobin (oxy-Hb) when listening to dissonant
      chords as compared with consonant chords, while the group without higher
      education for music did not show significant changes in oxy-Hb between consonant
      chords and dissonant chords. No significant  changes in oxy-Hb in the right
      auditory cortex were observed in response to either chord, neither in the group
      with higher education for music, nor in the group without it. DISCUSSION: Our
      results suggest that special musical training could enhance music-syntactic
      processing in the  left auditory area and react more sensitively to the dissonant
      chords.

PMID- 22642825
TI  - Tumor necrosis factor-alpha synthesis inhibitor 3,6'-dithiothalidomide attenuates
      markers of inflammation, Alzheimer pathology and behavioral deficits in animal
      models of neuroinflammation and Alzheimer's disease.
AB  - BACKGROUND: Neuroinflammation is associated with virtually all major
      neurodegenerative disorders, including Alzheimer's disease (AD). Although it
      remains unclear whether neuroinflammation is the driving force behind these
      disorders, compelling evidence implicates its role in exacerbating disease
      progression, with a key player being the potent proinflammatory cytokine TNF
      alpha. Elevated TNF-alpha levels are commonly detected in the clinic and animal
      models of AD. METHODS: The potential benefits of a novel TNF-alpha-lowering
      agent, 3,6'-dithiothalidomide, were investigated in cellular and rodent models of
      neuroinflammation with a specific focus on AD. These included central and
      systemic inflammation induced by lipopolysaccharide (LPS) and Abeta(1-42)
      challenge, and biochemical and behavioral assessment of 3xTg-AD mice following
      chronic 3,6'-dithiothaliodmide. RESULTS: 3,6'-Dithiothaliodmide lowered TNF
      alpha, nitrite (an indicator of oxidative damage) and secreted amyloid precursor
      protein (sAPP) levels in LPS-activated macrophage-like cells (RAW 264.7 cells).
      This translated into reduced central and systemic TNF-alpha production in acute
      LPS-challenged rats, and to a reduction of neuroinflammatory markers and
      restoration of neuronal plasticity following chronic central challenge of LPS. In
      mice centrally challenged with A(beta1-42) peptide, prior systemic 3,6'
      dithiothalidomide suppressed Abeta-induced memory dysfunction, microglial
      activation and neuronal degeneration. Chronic 3,6'-dithiothalidomide
      administration to an elderly symptomatic cohort of 3xTg-AD mice reduced multiple
      hallmark features of AD, including phosphorylated tau protein, APP, Abeta peptide
      and Abeta-plaque number along with deficits in memory function to levels present
      in younger adult cognitively unimpaired 3xTg-AD mice. Levels of the synaptic
      proteins, SNAP25 and synaptophysin, were found to be elevated in older
      symptomatic drug-treated 3xTg-AD mice compared to vehicle-treated ones,
      indicative of a preservation of synaptic function during drug treatment.
      CONCLUSIONS: Our data suggest a strong beneficial effect of 3,6'
      dithiothalidomide in the setting of neuroinflammation and AD, supporting a role
      for neuroinflammation and TNF-alpha in disease progression and their targeting as
      a means of clinical management.

PMID- 22642827
TI  - Relationships between the ABO blood group SNP rs505922 and breast cancer
      phenotypes: a genotype-phenotype correlation study.
AB  - BACKGROUND: To date, evaluation of the association of the ABO blood group and
      breast cancer has yielded mixed results. SNP rs505922, located within the first
      intron of the ABO gene, has been associated with the adenocarcinoma subtype of
      pancreatic cancer. To evaluate the association between genetic variation in the
      ABO blood group and risk of breast cancer, rs505922 was genotyped in 629
      Caucasian women with invasive breast cancer, representing a variety of clinical
      and pathological tumor types. METHODS: Genomic DNA was isolated from blood.
      TaqMan SNP assay C_2253769_10 was used to determine genotypes for each patient at
      rs505922. Statistical analysis was performed using chi-square analysis using a P
      value <0.05 to define significance. RESULTS: Genotypes were generated for 100% of
      the 629 patients in this study. Allele and genotype frequencies did not vary
      significantly for age at diagnosis, tumor stage, size or grade, hormone, HER2 or
      lymph node status, intrinsic subtype, tumor type or patient outcome. CONCLUSIONS:
      Allele frequencies for rs505922 did not differ between women with breast cancer
      and published HapMap frequencies from women of European descent. Further
      stratification into different tumor phenotypes also failed to reveal an
      association between rs505922 and any clinical characteristics. Together, these
      data suggest that the minor allele of rs505922 and the resulting non-O blood
      types are not associated with increased risk or less favorable tumor
      characteristics or prognosis in breast cancer.

PMID- 22642828
TI  - MRSA infections following colorectal surgery in an enhanced recovery programme.
AB  - AIM: The aim of this study was to evaluate the incidence of methicillin-resistant
      Staphylococcus aureus (MRSA) infections in a cohort of patients undergoing
      elective colorectal resections within an enhanced recovery programme. METHOD: A
      prospective database of all patients undergoing colorectal resections by a single
      surgical team over a 3.5-year period was reviewed. Demographics including age,
      gender, body mass index, American Society of Anesthesiologists classification,
      type of surgery (abdominal or pelvic) and whether or not the procedure was
      laparoscopic or open were analysed. All patients were screened preoperatively and
      postoperatively and on discharge for MRSA. Patients found preoperatively to be
      MRSA positive were excluded from the study. RESULTS: In all, 186 patients
      underwent colorectal resection over the time reviewed. There were 113
      laparoscopic resections, 70 open resections and three laparoscopic converted to
      open resections. Five patients (2.7%) were found to be MRSA positive
      postoperatively. All of these had open rather than laparoscopic surgery (P <
      0.01). Length of stay for patients that had MRSA infections was significantly
      longer than those remaining MRSA free (P < 0.05). CONCLUSION: These results
      suggest that patients who successfully undergo laparoscopic colorectal resections
      within an enhanced recovery programme have a lower incidence of postoperative
      MRSA infections.

PMID- 22642829
TI  - Pre-cooling and sports performance: a meta-analytical review.
AB  - Pre-cooling is used by many athletes for the purpose of reducing body temperature
      prior to exercise and, consequently, decreasing heat stress and improving
      performance. Although there are a considerable number of studies showing
      beneficial effects of pre-cooling, definite conclusions on the effectiveness of
      pre-cooling on performance cannot yet be drawn. Moreover, detailed analyses of
      the specific conditions under which pre-cooling may be most promising are, so
      far, missing. Therefore, we conducted a literature search and located 27 peer
      reviewed randomized controlled trials, which addressed the effects of pre-cooling
      on performance. These studies were analysed with regard to performance effects
      and several test circumstances (environmental temperature, test protocol, cooling
      method, aerobic capacity of the subjects). Eighteen studies were performed in a
      hot (>26 degrees C) environment and eight in a moderate. The cooling protocols
      were water application (n = 12), cooling packs (n = 3), cold drinks (n = 2),
      cooling vest (n = 6) and a cooled room (n = 4). The following different
      performance tests were used: short-term, high-intensity sprints (n = 2),
      intermittent sprints (n = 6), time trials (n = 10), open-end tests (n = 7) and
      graded exercise tests (n = 2). If possible, subjects were grouped into different
      aerobic capacity levels according to their maximal oxygen consumption (VO(2max)):
      medium 55-65 mL/kg/min (n = 11) and high >65 mL/kg/min (n = 6). For all studies
      the relative changes of performance due to pre-cooling compared with a control
      condition, as well as effect sizes (Hedges' g) were calculated. Mean values were
      weighted according to the number of subjects in each study. Pre-cooling had a
      larger effect on performance in hot (+6.6%, g = 0.62) than in moderate
      temperatures (+1.4%, g = 0.004). The largest performance enhancements were found
      for endurance tests like open-end tests (+8.6%, g = 0.52), graded exercise tests
      (+6.0%, g = 0.44) and time trials (+4.2%, g = 0.44). A similar effect was
      observed for intermittent sprints (+3.3%, g = 0.43), whereas performance changes
      were smaller during short-term, high-intensity sprints (-0.5%, g = 0.03). The
      most promising cooling methods were cold drinks (+15.0%, g = 1.68), cooling packs
      (+5.6%, g = 0.70) and a cooled room (+10.7%, g = 0.49), whereas a cooling vest
      (+4.8%, g = 0.31) and water application (+1.2%, g = 0.21) showed only small
      effects. With respect to aerobic capacity, the best results were found in the
      subjects with the highest VO(2max) (high +7.7%, g = 0.65; medium +3.8%, g =
      0.27). There were four studies analysing endurance-trained athletes under time
      trial conditions, which, in a practical sense, seem to be most relevant. Those
      studies found an average effect on performance of 3.7% (g = 0.48). In summary,
      pre-cooling can effectively enhance endurance performance, particularly in hot
      environments, whereas sprint exercise is barely affected. In particular, well
      trained athletes may benefit in a typical competition setting with practical and
      relevant effects. With respect to feasibility, cold drinks, cooling packs and
      cooling vests can be regarded as best-practice methods.

PMID- 22642830
TI  - Analysis of metabolic subnetworks by flux cone projection.
AB  - BACKGROUND: Analysis of elementary modes (EMs) is proven to be a powerful
      constraint-based method in the study of metabolic networks. However, enumeration
      of EMs is a hard computational task. Additionally, due to their large number, EMs
      cannot be simply used as an input for subsequent analysis. One possibility is to
      limit the analysis to a subset of interesting reactions. However, analysing an
      isolated subnetwork can result in finding incorrect EMs which are not part of any
      steady-state flux distribution of the original network. The ideal set to describe
      the reaction activity in a subnetwork would be the set of all EMs projected to
      the reactions of interest. Recently, the concept of "elementary flux patterns"
      (EFPs) has been proposed. Each EFP is a subset of the support (i.e., non-zero
      elements) of at least one EM. RESULTS: We introduce the concept of ProCEMs
      (Projected Cone Elementary Modes). The ProCEM set can be computed by projecting
      the flux cone onto a lower-dimensional subspace and enumerating the extreme rays
      of the projected cone. In contrast to EFPs, ProCEMs are not merely a set of
      reactions, but projected EMs. We additionally prove that the set of EFPs is
      included in the set of ProCEM supports. Finally, ProCEMs and EFPs are compared
      for studying substructures of biological networks. CONCLUSIONS: We introduce the
      concept of ProCEMs and recommend its use for the analysis of substructures of
      metabolic networks for which the set of EMs cannot be computed.

PMID- 22642831
TI  - Mechanistic and structural analyses of the role of His67 in the yeast polyamine
      oxidase Fms1.
AB  - The flavoprotein oxidase Fms1 from Saccharomyces cerevisiae catalyzes the
      oxidation of spermine and N(1)-acetylspermine to spermidine and 3-aminopropanal
      or N-acetyl-3-aminopropanal. Within the active site of Fms1, His67 is positioned
      to form hydrogen bonds with the polyamine substrate. This residue is also
      conserved in other polyamine oxidases. The catalytic properties of H67Q, H67N,
      and H67A Fms1 have been characterized to evaluate the role of this residue in
      catalysis. With both spermine and N(1)-acetylspermine as the amine substrate, the
      value of the first-order rate constant for flavin reduction decreases 2-3 orders
      of magnitude, with the H67Q mutation having the smallest effect and H67N the
      largest. The k(cat)/K(O2) value changes very little upon mutation with N(1)
      acetylspermine as the amine substrate and decreases only an order of magnitude
      with spermine. The k(cat)/K(M)-pH profiles with N(1)-acetylspermine are bell
      shaped for all the mutants; the similarity to the profile of the wild-type enzyme
      rules out His67 as being responsible for either of the pK(a) values. The pH
      profiles for the rate constant for flavin reduction for all the mutant enzymes
      similarly show the same pK(a) as wild-type Fms1, about ~7.4; this pK(a) is
      assigned to the substrate N4. The k(cat)/K(O2)-pH profiles for wild-type Fms1 and
      the H67A enzyme both show a pK(a) of about ~6.9; this suggests His67 is not
      responsible for this pH behavior. With the H67Q, H67N, and H67A enzymes the
      k(cat) value decreases when a single residue is protonated, as is the case with
      the wild-type enzyme. The structure of H67Q Fms1 has been determined at a
      resolution of 2.4 A. The structure shows that the mutation disrupts a hydrogen
      bond network in the active site, suggesting that His67 is important both for
      direct interactions with the substrate and to maintain the overall active site
      structure.

PMID- 22642832
TI  - Efficacy-mediated effects of spirituality and physical activity on quality of
      life: a path analysis.
AB  - BACKGROUND: Physical activity has been established as an important determinant of
      quality of life, particularly among older adults. Previous research has suggested
      that physical activity's influence on quality of life perceptions is mediated by
      changes in self-efficacy and health status. In the same vein, spirituality may be
      a salient quality of life determinant for many individuals. METHODS: In the
      current study, we used path analysis to test a model in which physical activity,
      spirituality, and social support were hypothesized to influence global quality of
      life in paths mediated by self-efficacy and health status. Cross-sectional data
      were collected from a sample of 215 adults (male, n = 51; female, n = 164) over
      the age of 50 (M age = 66.55 years). RESULTS: The analysis resulted in a model
      that provided acceptable fit to the data (chi2 = 33.10, df = 16, p < .01; RMSEA =
      .07; SRMR = .05; CFI = .94). CONCLUSIONS: These results support previous findings
      of an efficacy-mediated relationship between physical activity and quality of
      life, with the exception that self-efficacy in the current study was moderately
      associated with physical health status (.38) but not mental health status. Our
      results further suggest that spirituality may influence health and well-being via
      a similar, efficacy-mediated path, with strongest effects on mental health
      status. These results suggest that those who are more spiritual and physically
      active report greater quality of life, and the effects of these factors on
      quality of life may be partially mediated by perceptions of self-efficacy.

PMID- 22642833
TI  - Dok2 mediates the CD200Fc attenuation of Abeta-induced changes in glia.
AB  - BACKGROUND: The interaction between the membrane glycoprotein, CD200 and its
      cognate receptor CD200 receptor (CD200R), has been shown to play a role in
      maintaining microglia in a quiescent state. There is evidence of increased
      activation under resting and stimulated conditions in microglia prepared from
      CD200-deficient mice compared with wild-type mice, whereas activation of the
      receptor by CD200 fusion protein (CD200Fc) ameliorates inflammatory changes which
      are evident in the central nervous system (CNS) of the mouse model of multiple
      sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) and also in the
      hippocampus of aged rats. Additionally, an inverse relationship between
      microglial activation and expression of CD200 has been observed in animals
      treated with lipopolysaccharide (LPS) or amyloid-beta (Abeta). METHODS: We
      assessed the effect of CD200R activation by CD200Fc on Abeta-induced production
      of the pro-inflammatory cytokines, interleukin-1beta (IL-1beta) and tumor
      necrosis factor-alpha (TNFalpha) and the expression of microglial activation
      markers, CD68 and CD40 in cultured glia. The role played by downstream of
      tyrosine kinase 2 (Dok2) phosphorylation in mediating the effects of CD200R
      activation was evaluated by siRNA knockdown of Dok2. To further examine the
      impact of inflammatory changes on synaptic plasticity, the effect of CD200Fc on
      Abeta-induced impairment of long-term potentiation (LTP) in the CA1 region of
      hippocampal slices was also investigated. RESULTS: We demonstrate that Abeta
      induced increases in IL-1beta, TNFalpha, CD68 and CD40 were inhibited by CD200Fc.
      The evidence suggests that Dok2 phosphorylation is a key factor in mediating the
      effect of CD200Fc, since Dok2 knockdown by siRNA abrogated its effects on
      microglial activation and inflammatory cytokine production. Consistent with
      evidence that inflammatory changes negatively impact on LTP, we show that the
      Abeta-induced impairment of LTP was attenuated by CD200Fc. CONCLUSIONS: The
      findings suggest that activation of CD200R and Dok2 is a valuable strategy for
      modulating microglial activation and may have therapeutic potential in
      neurodegenerative conditions.

PMID- 22642835
TI  - Increasing crude and adjusted mortality rates for colorectal cancer in a
      developing South American country.
AB  - AIM: Colorectal cancer (CRC) is a major cause of cancer death worldwide. We
      examined temporal trends in death rates from colorectal cancer in Chile from 1983
      to 2008. METHOD: We analysed the mortality database in Chile from 1983 to 2008.
      Cases were selected using ICD-9/10 codes. We calculated mortality rates per
      100,000 inhabitants according to sex, age group and type of cancer - colon (CC)
      or rectal (RC). The rates were adjusted by a direct method using the WHO-2000
      standard population. Time trends were assessed with Prais-Winsten regression
      models. RESULTS: There were 26,250 deaths from CRC (75.7% for CC). There was a
      higher frequency of deaths from CC (57.6%) in women than in men, who had a higher
      frequency of deaths from RC (51.3%). The crude CC mortality rate increased by
      116% (from 3.6 to 7.8), while the overall RC rate increased by 71% (from 1.4 to
      2.4). After adjusting for age, a significant increase in mortality rate was found
      for CC (coefficient 0.09, 95% CI 0.08-0.11, P < 0.001) and RC (coefficient 0.02,
      95% CI 0.009-0.04, P = 0.002) in men. In women, this increase was significant for
      CC (coefficient 0.03, 95% CI 0.005-0.05; P = 0.02), but not for RC (coefficient 
      0.007, 95% CI -0.02 to 0.005, P = 0.23). CONCLUSION: The crude mortality rate
      from CRC has doubled in Chile in this period. After adjustment of mortality
      rates, it appears that much of this increase is due to the aging population.
      However, part of this increase could be explained by other factors.

PMID- 22642836
TI  - Estimation of the contributions of brake dust, tire wear, and resuspension to
      nonexhaust traffic particles derived from atmospheric measurements.
AB  - Size-fractionated samples of airborne particulate matter have been collected in a
      number of campaigns at Marylebone Road, London and simultaneously at background
      sites either in Regents Park or at North Kensington. Analysis of these samples
      has enabled size distributions of total mass and of a number of elements to be
      determined, and roadside increments attributable to nonexhaust emissions arising
      from traffic activity have been calculated. Taking a novel approach, the combined
      use of size distribution information and tracer elements has allowed the separate
      estimation of the contributions of brake dust, tire dust, and resuspension to
      particle mass in the range 0.9-11.5 MUm aerodynamic diameter and mean
      contributions (+/- s.e.) at the Marylebone Road sampling site are estimated as
      resuspended dust 38.1 +/- 9.7%, brake dust 55.3 +/- 7.0%, and tire dust 10.7 +/-
      2.3%, (accounting for a total of 104.1% of coarse particle mass in the traffic
      increment above background).

PMID- 22642834
TI  - Future directions in ADHD etiology research.
AB  - Reviews salient emerging themes in the scientific literature related to
      identifying etiology and pathophysiology of ADHD. While bypassing the need for
      new treatment research, the review highlights three themes. First, recognition of
      the epigenetic effects is expected to revitalize the search for and mapping of
      early environmental influences on the development of ADHD. Second,
      neurobiological findings will have limited impact if not examined in the context
      of significant race and cultural variation in ADHD-related developmental
      processes, and in the context of rapidly changing social and technological
      contexts of children's development worldwide. Third, further examination of the
      phenotype and characterization of its dimensional and categorical structure
      remains a major need. Overall, the coming decades of etiology research on ADHD
      will be expected to capitalize on new scientific tools. The hope in the field is
      that new insights into fundamental prevention can emerge.

PMID- 22642837
TI  - Phenytoin versus Leviteracetam for seizure prophylaxis after brain injury - a
      meta analysis.
AB  - BACKGROUND: Current standard therapy for seizure prophylaxis in Neuro-surgical
      patients involves the use of Phenytoin (PHY). However, a new drug Levetiracetam
      (LEV) is emerging as an alternate treatment choice. We aimed to conduct a meta
      analysis to compare these two drugs in patients with brain injury. METHODS: An
      electronic search was performed in using Pubmed, Embase, and CENTRAL. We included
      studies that compared the use of LEV vs. PHY for seizure prophylaxis for brain
      injured patients (Traumatic brain injury, intracranial hemorrhage, intracranial
      neoplasms, and craniotomy). Data of all eligible studies was extracted on to a
      standardized abstraction sheet. Data about baseline population characteristics,
      type of intervention, study design and outcome was extracted. Our primary outcome
      was seizures. RESULTS: The literature search identified 2489 unduplicated papers.
      Of these 2456 papers were excluded by reading the abstracts and titles. Another
      25 papers were excluded after reading their complete text. We selected 8 papers
      which comprised of 2 RCTs and 6 observational studies. The pooled estimate's Odds
      Ratio 1.12 (95% CI = 0.34, 3.64) demonstrated no superiority of either drug at
      preventing the occurrence of early seizures. In a subset analysis of studies in
      which follow up for seizures lasted either 3 or 7 days, the effect estimate
      remained insignificant with an odds ratio of 0.96 (95% CI = 0.34, 2.76).
      Similarly, 2 trials reporting seizure incidence at 6 months also had
      insignificant pooled results while comparing drug efficacy. The pooled odds ratio
      was 0.96 (95% CI = 0.24, 3.79). CONCLUSIONS: Levetiracetam and Phenytoin
      demonstrate equal efficacy in seizure prevention after brain injury. However,
      very few randomized controlled trials (RCTs) on the subject were found. Further
      evidence through a high quality RCT is highly recommended.

PMID- 22642838
TI  - Parsing trait and state effects of depression severity on neurocognition:
      Evidence from a 26-year longitudinal study.
AB  - Cognitive dysfunction in mood disorders falls along a continuum, such that more
      severe current depression is associated with greater cognitive impairment. It is
      not clear whether this association reflects transient state effects of current
      symptoms on cognitive performance, or persistent, trait-like differences in
      cognition that are related to overall disorder severity. We addressed this
      question in 42 unipolar and 47 bipolar participants drawn from a 26-year
      longitudinal study of psychopathology, using measures of attention/psychomotor
      processing speed, cognitive flexibility, verbal fluency, and verbal memory. We
      assessed (a) the extent to which current symptom severity and past average
      disorder severity predicted unique variance in cognitive performance; (b) whether
      cognitive performance covaried with within-individual changes in symptom
      severity; and (c) the stability of neurocognitive measures over six years. We
      also tested for differences among unipolar and bipolar groups and published
      norms. Past average depression severity predicted performance on
      attention/psychomotor processing speed in both groups, and in cognitive
      flexibility among unipolar participants, even after controlling for current
      symptom severity, which did not independently predict cognition. Within
      participant state changes in depressive symptoms did not predict change in any
      cognitive domain. All domains were stable over the course of six years. Both
      groups showed generalized impairment relative to published norms, and bipolar
      participants performed more poorly than unipolar participants on
      attention/psychomotor processing speed. The results suggest a stable relationship
      between mood disorder severity and cognitive deficits.

PMID- 22642840
TI  - Is interoceptive awareness really altered in somatoform disorders? Testing
      competing theories with two paradigms of heartbeat perception.
AB  - Alterations in the perception of body signals (i.e., interoceptive awareness
      [IA]) are considered crucial for the development and maintenance of somatoform
      disorders (SFDs). However, competing theories come to different conclusions about
      whether IA is increased or decreased in SFDs. The present study investigated IA
      in 23 patients with SFDs (as defined by the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition) and in 27 healthy controls. IA was reliably
      assessed with two well-established heartbeat perception paradigms (heartbeat
      discrimination task and mental tracking task). The results of both paradigms
      showed no evidence for increased IA in patients with SFDs. Correlational analyses
      revealed that having a higher number of somatoform symptoms was significantly
      linked to lower (rather than higher) IA in SFDs. These findings are in line with
      recent cognitive approaches to SFDs that stress the importance of biased schema
      guided processing of interoceptive information.

PMID- 22642839
TI  - Are tobacco dependence and withdrawal related amongst heavy smokers? Relevance to
      conceptualizations of dependence.
AB  - Measured tobacco dependence is typically only modestly related to tobacco
      withdrawal severity among regular smokers making a quit attempt. The weak
      association between dependence and withdrawal is notable because it conflicts
      with core theories of dependence and because both measures predict cessation
      outcomes, suggesting they both index a common dependence construct. This study
      used data from a smoking cessation comparative effectiveness trial (N = 1504) to
      characterize relations of tobacco dependence with craving and negative affect
      withdrawal symptoms using multiple dependence measures and analytic methods to
      detect both additive and interactive effects and to determine whether withdrawal
      meaningfully mediates the influence of dependence on smoking cessation. We
      conclude: (a) Although univariate analyses suggest dependence and withdrawal
      measures are only modestly interrelated, more powerful analytic techniques show
      they are, in fact, meaningfully related and their shared variance is associated
      with cessation likelihood; (b) there are clear differences between craving and
      negative affective withdrawal symptoms, with the former more related to smoking
      heaviness and the latter related to trait measures of negative affect; moreover,
      craving more strongly mediates dependence effects on cessation; and (c) both
      craving and negative affect withdrawal symptoms are strongly related to a pattern
      of regular smoking that is sensitive to the passage of time and powerfully
      affected by smoking cues. These findings support models that accord an important
      role for associative processes and withdrawal symptoms, especially craving, in
      drug dependence. The findings also support the use of withdrawal variables as
      criteria for the evaluation of dependence measures.

PMID- 22642842
TI  - Somatic symptom reporting has a dimensional latent structure: results from
      taxometric analyses.
AB  - Medically unexplained symptoms (MUS) are one of the key features of somatoform
      disorders. Although MUS are currently treated as both categorical (in terms of
      the diagnosis of somatoform disorders) and dimensional (in terms of quantitative
      measures of somatization/somatic symptom reporting), little is known about the
      empirical latent structure of MUS. Using taxometric analyses, the latent
      structure of somatic symptom reporting was analyzed with the Patient Health
      Questionnaire (PHQ)-15 in two student samples (N=782 and N=2,577) and a primary
      care sample (N=519). We applied three popular taxometric methods: Maximum
      Eigenvalue (MAXEIG), Mean Above Minus Below a Cut (MAMBAC) and Latent-Mode (L
      Mode). Simulation data were created to evaluate the appropriateness of the data
      for our analyses and to create the comparison curve fit index (CCFI) as an
      objective outcome measure. The results of all taxometric methods in any of the
      three data sets were in favor of a dimensional solution (CCFI<.50). Simulated
      taxonic and dimensional datasets differed substantially and the samples were
      appropriate for taxometric analysis. Accordingly, the latent structure of
      somatization/somatic symptom reporting as assessed by the PHQ-15 is dimensional
      in both primary care and student samples. Implications regarding the practical
      application as well as models of etiology and pathogenesis of somatic symptom
      reporting are discussed.

PMID- 22642841
TI  - Serotonin transporter gene as a predictor of stress generation in depression.
AB  - Research suggests that a polymorphism in the promoter region of the serotonin
      transporter promoter (5-HTTLPR) interacts with stressful life events to predict
      depressive onset, with short (s) allele presence associated with greater
      susceptibility to stressors. However, this research has not considered that
      depressed individuals often actively generate stressful contexts. Furthermore,
      little is known about the genetic basis of stress generation. The current study
      explored the role of 5-HTTLPR genotype in stress generation in a longitudinal
      sample of 381 adolescents, oversampled for maternal depression, assessed at ages
      15 and 20. Genotype did not correlate directly with number or ratings of
      stressful life events. However, 5-HTTLPR genotype interacted with depression at
      age 15 to predict dependent stressful events at age 20. Specifically,
      participants with one or more s alleles showed a stronger association between age
      15 depression and age 20 dependent and interpersonal events than long allele
      homozygotes. Results imply that the 5-HTTLPR genotype predicts reciprocal
      associations between stress and depression, indicating a more complex
      relationship between stress, depression, and their genetic underpinnings than
      previously suggested.

PMID- 22642843
TI  - Genetic diversity among Curtobacterium flaccumfaciens pv. flaccumfaciens
      populations in the American high plains.
AB  - Curtobacterium flaccumfaciens  pv. flaccumfaciens is a Gram-positive bacterium
      and has reemerged as an incitant of bacterial wilt in common (dry, edible) beans
      in western Nebraska, eastern Colorado, and southeastern Wyoming. Curtobacterium
      flaccumfaciens pv. flaccumfaciens is diverse phenotypically and genotypically and
      is represented by several different pathogen color variants. The population
      structure of 67 strains collected between 1957 and 2009, including some isolated
      from alternate hosts, was determined with 3 molecular typing techniques:
      amplified fragment length polymorphism (AFLP), repetitive extragenic palindromic
      polymerase chain reaction (rep-PCR), and pulsed-field gel electrophoresis (PFGE).
      All 3 typing techniques showed a great degree of population heterogeneity, but
      they were not congruent in cluster analysis of the C. flaccumfaciens pv.
      flaccumfaciens populations. Cluster analysis of a composite data set (AFLP, PFGE,
      and rep-PCR) using averages from all experiments yielded 2 distinct groups:
      cluster A included strains with colonies of yellow, orange, and pink pigments,
      and cluster B had strains of only yellow pigment. Strains producing purple
      extracellular pigment were assigned to both clusters. Thus, C. flaccumfaciens pv.
      flaccumfaciens is diverse phenotypically and genotypically.

PMID- 22642844
TI  - Aortic valve stenosis after previous coronary bypass: transcatheter valve
      implantation or aortic valve replacement?
AB  - We report a prospective comparison between transcatheter valve implantation
      (TAVI, n = 13) and surgical aortic valve replacement (AVR, n = 10) in patients
      with severe aortic valve stenosis and previous coronary bypass surgery (CABG).
      All patients had at least bilateral patent internal thoracic arteries bypass
      without indication of repeat revascularization. After a similar post-procedure
      outcome, despite one early death in TAVI group, the 1-year survival was 100% in
      surgical group and in transfemoral TAVI group, and 73% in transapical TAVI group.
      When previous CABG is the lone surgical risk factor, indications for a TAVI
      procedure have to be cautious, specially if transfemoral approach is not
      possible.

PMID- 22642845
TI  - Hyperoxia preconditioning: the next frontier in neurology?
AB  - Oxygen is indispensable for all aerobic organisms and has become one of the most
      widely used therapeutic agents. Currently, oxygen not only is applied in the
      treatment of diseases, but becomes a modality for the prevention of some
      diseases. Hyperoxia preconditioning with normobaric  or hyperbaric oxygen has
      been found to be protective in some diseases in several animal models and
      clinical trials. Currently, investigators pay increasing attention to the
      application of hyperoxia preconditioning in the prevention of common neurological
      diseases, and encouraging effectiveness  has been achieved. In the present short
      review, we briefly described the development, application and mechanisms of
      hyperoxia preconditioning in the neurology, and the issues in future application
      of hyperoxia preconditioning were also proposed.

PMID- 22642846
TI  - Differential Ca(2+) sensor guanylate cyclase activating protein modes of
      photoreceptor rod outer segment membrane guanylate cyclase signaling.
AB  - Photoreceptor ROS-GC1 (rod outer segment membrane guanylate cyclase) is a vital
      component of phototransduction. It is a bimodal Ca(2+) signal transduction
      switch, operating between 20 and ~1000 nM. Modulated by Ca(2+) sensors guanylate
      cyclase activating proteins 1 and 2 (GCAP1 and GCAP2, respectively), decreasing
      [Ca(2+)](i) from 200 to 20 nM progressively turns it "on", as does the modulation
      by the Ca(2+) sensor S100B, increasing [Ca(2+)](i) from 100 to 1000 nM. The GCAP
      mode plays a vital role in phototransduction in both rods and cones and the S100B
      mode in the transmission of neural signals to cone ON-bipolar cells. Through a
      programmed domain deletion, expression, in vivo fluorescence spectroscopy, and in
      vitro reconstitution experiments, this study demonstrates that the biochemical
      mechanisms modulated by two GCAPs in Ca(2+) signaling of ROS-GC1 activity are
      totally different. (1) They involve different structural domains of ROS-GC1. (2)
      Their signal migratory pathways are opposite: GCAP1 downstream and GCAP2
      upstream. (3) Importantly, the isolated catalytic domain, translating the GCAP
      modulated Ca(2+) signal into the generation of cyclic GMP, in vivo, exists as a
      homodimer, the two subunits existing in an antiparallel conformation.
      Furthermore, the findings demonstrate that the N-terminally placed signaling
      helix domain is not required for the catalytic domain's dimeric state. The
      upstream GCAP2-modulated pathway is the first of its kind to be observed for any
      member of the membrane guanylate cyclase family. It defines a new model of Ca(2+)
      signal transduction.

PMID- 22642847
TI  - ASD, a psychiatric disorder, or both? Psychiatric diagnoses in adolescents with
      high-functioning ASD.
AB  - Varied presentations of emotion dysregulation in autism complicate diagnostic
      decision making and may lead to inaccurate psychiatric diagnoses or delayed
      autism diagnosis for high-functioning children. This pilot study aimed to
      determine the concordance between prior psychiatric diagnoses and the results of
      an autism-specific psychiatric interview in adolescents with high-functioning
      autism. Participants included 35 predominantly Caucasian and male verbal 10- to
      17-year-olds with a confirmed autism spectrum disorder and without intellectual
      disability. The average age of autism spectrum diagnosis was 11 years old.
      Lifetime psychiatric diagnoses were established via the Autism Comorbidity
      Interview, developed to identify comorbid conditions within the context of
      autism. Autism Comorbidity Interview results were compared to parent report of
      prior community psychiatric diagnoses. Approximately 60% of prior psychiatric
      diagnoses were not supported on the Autism Comorbidity Interview; the lowest
      diagnostic concordance was for prior bipolar disorder and obsessive-compulsive
      disorder diagnoses. Although 51% of children met Autism Comorbidity Interview
      criteria for at least one psychiatric disorder, rates of prior diagnoses were
      much higher, with 77% having at least one prior psychiatric diagnosis and 60%
      having two or more. Although many participants met criteria for comorbid
      psychiatric disorders, the majority of previous psychiatric diagnoses were not
      supported when autism-related manifestations were systematically taken into
      account. These findings require replication and may not generalize to lower
      functioning and earlier diagnosed children with autism spectrum disorder. Results
      emphasize the importance of increasing awareness of the manifestations of high
      functioning autism in order to improve accuracy of diagnosis and appropriateness
      of interventions.

PMID- 22642849
TI  - Chemical effectors cause different motile behavior and deposition of bacteria in
      porous media.
AB  - We tested the hypothesis whether chemically induced motility patterns of bacteria
      may affect their transport in porous media. Naphthalene-degrading Pseudomonas
      putida G7 cells were exposed to glucose, salicylate, and silver nanoparticles
      (AgNPs) and their motility was assessed by computer-assisted, quantitative
      swimming and capillary-based taxis determinations. Exposure to salicylate induced
      smooth movement with few acceleration events and positive taxis, whereas cells
      exposed to AgNPs exhibited tortuous movement and a repellent response. Although
      metabolized by strain G7, glucose did not cause attraction and induced a hyper
      motile mode of swimming, characterized by a high frequency of acceleration
      events, high swimming speed (>60 MUm s(-1)), and a high tortuosity in the
      trajectories. Chemically induced motility behavior correlated with distinct modes
      of attachment to sand in batch assays and breakthrough curves in percolation
      column experiments. Salicylate significantly reduced deposition of G7 cells in
      column experiments whereas glucose and AgNPs enhanced attachment and caused
      filter blocking that resulted in a progressive decrease in deposition. These
      findings are relevant for bioremediation scenarios that require an optimized
      outreach of introduced inoculants and in other environmental technologies, such
      as water disinfection and microbially enhanced oil recovery.

PMID- 22642848
TI  - Prokineticin 2 potentiates acid-sensing ion channel activity in rat dorsal root
      ganglion neurons.
AB  - BACKGROUND: Prokineticin 2 (PK2) is a secreted protein and causes potent
      hyperalgesia in vivo, and is therefore considered to be a new pronociceptive
      mediator. However, the molecular targets responsible for the pronociceptive
      effects of PK2 are still poorly understood. Here, we have found that PK2
      potentiates the activity of acid-sensing ion channels in the primary sensory
      neurons. METHODS: In the present study, experiments were performed on neurons
      freshly isolated from rat dorsal root ganglion by using whole-cell patch clamp
      and voltage-clamp recording techniques. RESULTS: PK2 dose-dependently enhanced
      proton-gated currents with an EC50 of 0.22 +/- 0.06 nM. PK2 shifted the proton
      concentration-response curve upwards, with a 1.81 +/- 0.11 fold increase of the
      maximal current response. PK2 enhancing effect on proton-gated currents was
      completely blocked by PK2 receptor antagonist. The potentiation was also
      abolished by intracellular dialysis of GF109203X, a protein kinase C inhibitor,
      or FSC-231, a protein interacting with C-kinase 1 inhibitor. Moreover, PK2
      enhanced the acid-evoked membrane excitability of rat dorsal root ganglion
      neurons and caused a significant increase in the amplitude of the depolarization
      and the number of spikes induced by acid stimuli. Finally, PK2 exacerbated
      nociceptive responses to the injection of acetic acid in rats. CONCLUSION: These
      results suggest that PK2 increases the activity of acid-sensing ion channels via
      the PK2 receptor and protein kinase C-dependent signal pathways in rat primary
      sensory neurons. Our findings support that PK2 is a proalgesic factor and its
      signaling likely contributes to acidosis-evoked pain by sensitizing acid-sensing
      ion channels.

PMID- 22642850
TI  - A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline
      resectable locally advanced pancreatic adenocarcinoma.
AB  - BACKGROUND: 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX)
      is superior to gemcitabine in patients with metastatic pancreatic cancer who have
      a good performance status. We investigated this combination as neoadjuvant
      therapy for locally advanced pancreatic cancer (LAPC). METHODS: In this
      retrospective series, we included patients with unresectable LAPC who received
      neoadjuvant FOLFIRINOX with growth factor support. The primary analysis endpoint
      was R0 resection rate. RESULTS: Eighteen treatment-naive patients with
      unresectable or borderline resectable LAPC were treated with neoadjuvant
      FOLFIRINOX. The median age was 57.5 years and all had ECOG PS of 0 or 1. Eleven
      (61 %) had tumors in the head of the pancreas and 9 (50 %) had biliary stents
      placed prior to chemotherapy. A total of 146 cycles were administered with a
      median of 8 cycles (range 3-17) per patient. At maximum response or tolerability,
      7 (39 %) were converted to resectability by radiological criteria; 5 had R0
      resections, 1 had an R1 resection, and 1 had unresectable disease. Among the 11
      patients who remained unresectable after FOLFIRINOX, 3 went on to have R0
      resections after combined chemoradiotherapy, giving an overall R0 resection rate
      of 44 % (95 % CI 22-69 %). After a median follow-up of 13.4 months, the 1-year
      progression-free survival was 83 % (95 % CI 59-96 %) and the 1-year overall
      survival was 100 % (95 % CI 85-100 %). Grade 3/4 chemotherapy-related toxicities
      were neutropenia (22 %), neutropenic fever (17 %), thrombocytopenia (11 %),
      fatigue (11 %), and diarrhea (11 %). Common grade 1/2 toxicities were neutropenia
      (33 %), anemia (72 %), thrombocytopenia (44 %), fatigue (78 %), nausea (50 %),
      diarrhea (33 %) and neuropathy (33 %). CONCLUSIONS: FOLFIRINOX followed by
      chemoradiotherapy is feasible as neoadjuvant therapy in patients with
      unresectable LAPC. The R0 resection rate of 44 % in this population is promising.
      Further studies are warranted.

PMID- 22642851
TI  - Quality of life and sexual function 1 year after laparoscopic rectosigmoid
      resection for endometriosis.
AB  - AIM: Endometriosis is relatively common condition in fertile women and may affect
      the alimentary tract. Laparoscopic rectosigmoid resection for endometriosis has
      been found to be both feasible and safe. The aim of the present study was to
      prospectively evaluate the quality of life and sexual function of patients who
      have undergone rectosigmoid resection for endometriosis. METHOD: All patients
      undergoing rectal or sigmoid resection for endometriosis in two specialist
      hospitals were prospectively recruited in the study. Details regarding
      demography, endometriosis-related symptoms, procedure and postoperative recovery
      were collected. One year after the operation patients were sent a postal
      questionnaire asking about endometriosis-related symptoms, quality of life and
      sexual functioning. The 15D Questionnaire and McCoy Female Sexuality
      Questionnaire were used for this purpose. RESULTS: A total of 26 patients
      responded to the 15D questionnaire. Endometriosis-related bowel symptoms
      decreased significantly after the operation. The responses showed improvements in
      the overall score and scores for five different dimensions (usual activities, P =
      0.04; discomfort and symptoms, P < 0.001; distress, P < 0.001; vitality, P <
      0.001; sexual activity, P < 0.001). Sexual satisfaction was greater 1 year after
      the operation (P = 0.01). Sexual problems and partner satisfaction scores had not
      changed significantly. CONCLUSION: Laparoscopic rectal and sigmoid resection for
      endometriosis significantly reduce endometriosis-related symptoms and improve
      quality of life and sexual well-being.

PMID- 22642853
TI  - Assessing motivational interviewing integrity for group interventions with
      adolescents.
AB  - The group format is commonly used in alcohol and other drug (AOD) adolescent
      treatment settings, but little research exists on the use of motivational
      interviewing (MI) in groups. Further, little work has assessed the integrity of
      MI delivered in group settings. This study describes an approach to evaluate MI
      integrity using data from a group MI intervention for at-risk youth. Using the
      Motivational Interviewing Treatment Integrity (MITI) scale, version 3.1, we coded
      140 group sessions led by 3 different facilitators. Four trained coders assessed
      the group sessions. Agreement between raters was evaluated using a method based
      on limits of agreement, and key decisions used to monitor and calculate group MI
      integrity are discussed. Results indicated that there was adequate agreement
      between raters; we also found differences on use of MI between the MI
      intervention group and a usual-care group on MI global ratings and behavioral
      counts. This study demonstrates that it is possible to determine whether group MI
      is implemented with integrity in the group setting and that MI in this setting is
      different from what takes place in usual care.

PMID- 22642854
TI  - Survey of providers' attitudes toward integrating smoking cessation treatment
      into posttraumatic stress disorder care.
AB  - A survey was administered anonymously to 45 mental health providers who delivered
      smoking cessation treatment integrated into posttraumatic stress disorder care
      (integrated care) as part of a multisite clinical trial. Survey items assessed
      key factors associated with successful implementation of research-based practices
      from the perspective of treating providers. Factors assessed included prior
      experiences with cessation treatment, compatibility of integrated care with
      current practices, feasibility of adopting integrated care into regular practice,
      and adequacy of training. More than half of respondents reported that integrated
      care delivery was feasible, and they would be considerably or extremely likely to
      continue delivery in routine practice. Positive prestudy beliefs and more
      experience delivering cessation care were associated with stronger endorsement of
      delivering integrated care after the study. The most frequently cited obstacle to
      delivering integrated care involved time limitations. Future efforts should focus
      on developing treatment adaptations that address provider-identified barriers and
      identifying clinic- and administrative-level supports that facilitate delivery of
      integrated care and assist providers who incorporate integrated care into
      clinical practice.

PMID- 22642855
TI  - Effects of alcohol on sequential information processing: evidence for temporal
      myopia.
AB  - Alcohol Myopia Theory (AMT) posits that alcohol restricts the focus of attention,
      such that behaviors are determined only by highly salient environmental cues.
      While AMT is most commonly understood in terms of spatial attention, the present
      study tested the effects of alcohol in the temporal domain of attention. Seventy
      one participants consumed either a placebo beverage or one of two doses of
      alcohol (0.40g/kg or 0.80g/kg ETOH) before performing an auditory discrimination
      task while event-related potentials (ERPs) were recorded. Consistent with typical
      sequential effects, placebo participants showed increased P300 amplitude and
      slowed behavioral responses when the current target differed from the two-back
      tone. In contrast, alcohol caused increased P300 and response slowing when the
      target tone differed from the one-back tone. These findings suggest that alcohol
      increases the salience of more recently encountered information, consistent with
      the general tenets of AMT.

PMID- 22642856
TI  - The Short Inventory of Problems - revised (SIP-R): psychometric properties within
      a large, diverse sample of substance use disorder treatment seekers.
AB  - Assessment of the adverse consequences of substance use serves an important
      function in both clinical and research settings, yet there is no universally
      agreed upon measure of consequences relevant to multiple types of substance use
      disorders. One of the most commonly used measures, the Short Inventory of
      Problems (SIP), has been adapted and evaluated in several specific populations,
      but evidence is needed of its reliability and validity across broader samples of
      persons with substance use disorders. This study evaluated the psychometric
      properties of a revised version of the SIP (SIP-R) in a large combined sample of
      alcohol and drug use disorder treatment seekers, with participants pooled from
      two national, multisite, randomized clinical trials. A total of 886 participants
      across 10 outpatient treatment facilities completed a common assessment battery
      that included the SIP-R, Addiction Severity Index (ASI), University of Rhode
      Island Change Assessment (URICA), HIV Risk Behavior Scale (HRBS), and a substance
      use calendar. Results supported the SIP-R's internal reliability (alpha = .95).
      Confirmatory factor analysis demonstrated that the hypothesized 5-factor model
      with one higher-order factor produced the best fit. Convergent validity was
      evident through the SIP-R's correlation with several composite scores from the
      ASI and the URICA, and analyses supported its conceptual distinction from
      quantity indices of drug/alcohol use. The SIP-R also demonstrated an ability to
      predict treatment retention, with higher scores associated with poorer retention.
      These results provide support for the SIP-R's psychometric properties as a
      measure of consequences across a broad sample of treatment-seeking drug and
      alcohol users.

PMID- 22642857
TI  - A working memory bias for alcohol-related stimuli depends on drinking score.
AB  - We tested 44 participants with respect to their working memory (WM) performance
      on alcohol-related versus neutral visual stimuli. Previously an alcohol
      attentional bias (AAB) had been reported using these stimuli, where the attention
      of frequent drinkers was automatically drawn toward alcohol-related items (e.g.,
      beer bottle). The present study set out to provide evidence for an alcohol memory
      bias (AMB) that would persist over longer time-scales than the AAB. The WM task
      we used required memorizing 4 stimuli in their correct locations and a visual
      interference task was administered during a 4-sec delay interval. A subsequent
      probe required participants to indicate whether a stimulus was shown in the
      correct or incorrect location. For each participant we calculated a drinking
      score based on 3 items derived from the Alcohol Use Questionnaire, and we
      observed that higher scorers better remembered alcohol-related images compared
      with lower scorers, particularly when these were presented in their correct
      locations upon recall. This provides first evidence for an AMB. It is important
      to highlight that this effect persisted over a 4-sec delay period including a
      visual interference task that erased iconic memories and diverted attention away
      from the encoded items, thus the AMB cannot be reduced to the previously reported
      AAB. Our finding calls for further investigation of alcohol-related cognitive
      biases in WM, and we propose a preliminary model that may guide future research.

PMID- 22642858
TI  - Isolating the role of psychological dysfunction in smoking cessation: relations
      of personality and psychopathology to attaining cessation milestones.
AB  - Research exploring psychological dysfunction as a predictor of smoking cessation
      success may be limited by nonoptimal predictor variables (i.e., categorical
      psychodiagnostic measures vs. continuous personality-based manifestations of
      dysfunction) and imprecise outcomes (i.e., summative point-prevalence abstinence
      vs. constituent cessation milestone measures). Accordingly, this study evaluated
      the unique and overlapping relations of broad-spectrum personality traits
      (positive emotionality, negative emotionality, and constraint) and past-year
      psychopathology (anxiety, mood, and substance use disorder) to point-prevalence
      abstinence and three smoking cessation milestones: (a) initiating abstinence, (b)
      first lapse, and (c) transition from lapse to relapse. Participants were daily
      smokers (N = 1365) enrolled in a smoking cessation treatment study. In single
      predictor regression models, each manifestation of internalizing dysfunction
      (lower positive emotionality, higher negative emotionality, and anxiety and mood
      disorder) predicted failure at one or more cessation milestone(s). In
      simultaneous predictor models, lower positive and higher negative emotionality
      significantly predicted failure to achieve milestones after controlling for
      psychopathology. Psychopathology did not predict any outcome when controlling for
      personality. Negative emotionality showed the most robust and consistent effects,
      significantly predicting failure to initiate abstinence, earlier lapse, and lower
      point-prevalence abstinence rates. Substance use disorder and constraint did not
      predict cessation outcomes, and no single variable predicted lapse-to-relapse
      transition. These findings suggest that personality-related manifestations of
      internalizing dysfunction are more accurate markers of affective sources of
      relapse risk than mood and anxiety disorders. Further, individuals with high
      trait-negative emotionality may require intensive intervention to promote the
      initiation and early maintenance of abstinence.

PMID- 22642859
TI  - Craving to quit: psychological models and neurobiological mechanisms of
      mindfulness training as treatment for addictions.
AB  - Humans suffer heavily from substance use disorders and other addictions. Despite
      much effort that has been put into understanding the mechanisms of the addictive
      process, treatment strategies have remained suboptimal over the past several
      decades. Mindfulness training, which is based on ancient Buddhist models of human
      suffering, has recently shown preliminary efficacy in treating addictions. These
      early models show remarkable similarity to current models of the addictive
      process, especially in their overlap with operant conditioning (positive and
      negative reinforcement). Further, they may provide explanatory power for the
      mechanisms of mindfulness training, including its effects on core addictive
      elements, such as craving, and the underlying neurobiological processes that may
      be active therein. In this review, using smoking as an example, we will highlight
      similarities between ancient and modern views of the addictive process, review
      studies of mindfulness training for addictions and their effects on craving and
      other components of this process, and discuss recent neuroimaging findings that
      may inform our understanding of the neural mechanisms of mindfulness training.

PMID- 22642860
TI  - Task persistence predicts smoking cessation in smokers with and without
      schizophrenia.
AB  - Smokers attempting to quit should benefit from persisting in cognitive and
      behavioral coping in order to achieve and maintain abstinence. Task persistence,
      which describes the act of persisting in a difficult or effortful task, is likely
      to be required in the face of distressing smoking cues, urges to smoke, or other
      nicotine withdrawal symptoms. This study examined whether task persistence (also
      called distress tolerance) could prospectively predict smoking cessation in a
      mixed sample of smokers with and without schizophrenia. Smokers with
      schizophrenia or schizoaffective disorder (n = 71) and nonpsychiatric smokers (n
      = 78) seeking treatment at state-funded tobacco dependence treatment clinics
      completed tests of task persistence before their target quit date, and then
      provided tobacco use data over the 6 months after their quit date. Findings from
      generalized estimating equations support the hypothesis that task persistence as
      measured by a mirror-tracing task predicts smoking cessation while controlling
      for important covariates such as psychiatric diagnosis, nicotine dependence, and
      confidence in ability to quit. These findings add to the literature by
      corroborating reports suggesting that task persistence may make important
      contributions to smoking cessation success, and by indicating that the
      contribution of task persistence to smoking cessation is similar for smokers with
      schizophrenia and nonpsychiatric smokers. These results suggest that efforts to
      target task persistence in smoking cessation counseling protocols may be
      warranted.

PMID- 22642861
TI  - Social support and comfort in AA as mediators of "Making AA easier" (MAAEZ), a 12
      step facilitation intervention.
AB  - A trial of "Making Alcoholics Anonymous Easier" (MAAEZ), a group-format 12-step
      facilitation program, showed significantly higher odds of past 30-day abstinence
      after 12 months among those who had been treated in MAAEZ compared to usual care,
      especially for clients with high prior AA/NA/CA meeting attendance (>90 prior
      meetings; OR = 2.94, p = .02). We examined whether MAAEZ effects for this group
      were mediated by social support for sobriety and comfort with the 12-step
      fellowship. Among those with high prior AA/NA/CA attendance, we performed tests
      of multiple mediation to estimate MAAEZ effects attributable to the combined
      effect of social network support for sobriety, comfort being at AA/NA/CA
      meetings, and comfort speaking at AA/NA/CA meetings. To gain some understanding
      of sustaining these behaviors, we also examined each potential mediating variable
      measured both prior to, and concurrent with, 12-month outcomes. Having support
      for sobriety at 6 months emerged as a mediator of 12-month MAAEZ effects, when
      controlling for comfort being and speaking at AA/NA/CA meetings at 6 months. The
      effect remained when controlling for mediator values at 12 months, and explained
      44% of the MAAEZ effect. Results highlight the value of studying specific,
      modifiable 12-step activities, and demonstrate the importance of exploring
      subgroups to determine behaviors and attitudes to target for optimal treatment.
      For example, increasing support for sobriety among those with high prior AA/NA/CA
      attendance may be especially pertinent.

PMID- 22642862
TI  - Capacity for cognitive and emotional empathy in alcohol-dependent patients.
AB  - This study assessed two previously unexplored facets of empathy in alcohol
      dependent patients (ADs) divided into two groups according to Cloninger's
      alcoholism typology: the attribution of intentions according to emotional facial
      expressions (EFEs) and emotional contagion in reaction to EFEs. Twenty-three male
      Type-I ADs, 21 male Type-II ADs, and 24 male control participants were compared
      in two computerized tasks. First, participants rated the extent to which an
      adjective descriptive of personality weighted on interpersonal dimensions (of
      rejection, aggressiveness, dominance, and affiliation) corresponded with a video
      of a neutral EFE that changed to an intense EFE. Second, participants evaluated
      their own emotional states after watching a series of videos that depicted EFEs
      while their own face was being filmed. The results showed that Type-I ADs
      attributed more rejection intentions and fewer affiliation intentions to EFEs
      compared with controls; however, depression might better explain this biased
      attribution. Furthermore, AD subtypes showed a different pattern of intention
      attribution according to the emotions that were portrayed and the sex of the
      stimulus. In addition, angry EFE mimicry was stronger in Type-II ADs than other
      participants. Finally, ADs expressed fewer positive emotions and more negative
      emotions than controls when watching EFEs. These findings emphasize the
      importance of differentiating alcoholism subtypes and contribute to the
      understanding of AD interpersonal behaviors.

PMID- 22642863
TI  - Superior reinforcement effect of TEMPO-oxidized cellulose nanofibrils in
      polystyrene matrix: optical, thermal, and mechanical studies.
AB  - Polystyrene (PS) composites reinforced with 2,2,6,6-tetramethylpiperidine-1-oxyl
      (TEMPO)-oxidized cellulose nanofibrils (TOCNs) with various weight ratios were
      fabricated by casting and vacuum-drying mixtures of PS/N,N-dimethylformamide
      (DMF) solution and TOCN/DMF dispersion. TOCNs of 3 to 4 nm width were dispersed
      homogeneously at the individual nanofibril level in the PS matrix, such that the
      TOCN/PS nanocomposite films exhibited high optical transparencies and their
      tensile strengths, elastic moduli, and thermal dimensional stabilities increased
      with increasing TOCN content. Dynamic mechanical analysis showed that the storage
      modulus of the TOCN/PS films increased significantly with TOCN content above the
      glass-transition temperature of PS by the formation of an interfibrillar network
      structure of TOCNs in the PS matrix, based on percolation theory. The outstanding
      and effective polymer reinforcement by TOCNs results from their high aspect
      ratio, high crystallinity, and nanodispersibility in the PS matrix.

PMID- 22642864
TI  - Evaluation of classification systems for nonspecific idiopathic orbital
      inflammation.
AB  - PURPOSE: To systematically analyze existing classification systems for idiopathic
      orbital inflammation (IOI) and propose and test a new best practice
      classification system. METHODS: A systematic literature search was conducted to
      find all studies that described and applied a classification system for IOI.
      Classification categories used in more than two studies were extracted, and
      criteria for these categories were defined using common descriptors. Using
      patient data, these newly defined classification systems were evaluated.
      Reliability was tested by inter- and intrarater agreement of two raters and
      distinction tested by evaluating clinical differences among classification
      categories. Feasibility, face validity, and content validity were qualitatively
      tested. RESULTS: The most frequently encountered IOI classification systems were
      based on onset (acute, chronic), histopathology (classic, granulomatous,
      sclerosing), or localization (diffuse, extraocular muscle, lacrimal gland,
      sclera, optic nerve). Systems based on histopathology and localization showed
      good reliability (kappa values range 0.74-0.89), were easy to apply
      (feasibility), and described the biologic process (face validity). Because of
      static sampling, histopathology-based systems had moderate content validity and
      moderate distinction between classification categories. Being a static measure,
      localization had moderate content validity, but good distinction. It was found
      that content validity was improved by combining histopathology and localization
      into a two-dimensional classification system. CONCLUSIONS: This combined
      histopathology and localization-based classification system provides a
      repeatable, easy to use, plausible, and complete classification system that can
      be used to further advance the research of IOI.

PMID- 22642865
TI  - 3-methylcrotonyl-CoA carboxylase deficiency: clinical, biochemical, enzymatic and
      molecular studies in 88 individuals.
AB  - BACKGROUND: Isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is an
      autosomal recessive disorder of leucine metabolism caused by mutations in MCCC1
      or MCCC2 encoding the alpha and beta subunit of MCC, respectively. The phenotype
      is highly variable ranging from acute neonatal onset with fatal outcome to
      asymptomatic adults. METHODS: We report clinical, biochemical, enzymatic and
      mutation data of 88 MCC deficient individuals, 53 identified by newborn
      screening, 26 diagnosed due to clinical symptoms or positive family history and 9
      mothers, identified following the positive newborn screening result of their
      baby. RESULTS: Fifty-seven percent of patients were asymptomatic while 43% showed
      clinical symptoms, many of which were probably not related to MCC deficiency but
      due to ascertainment bias. However, 12 patients (5 of 53 identified by newborn
      screening) presented with acute metabolic decompensations. We identified 15 novel
      MCCC1 and 16 novel MCCC2 mutant alleles. Additionally, we report expression
      studies on 3 MCCC1 and 8 MCCC2 mutations and show an overview of all 132 MCCC1
      and MCCC2 variants known to date. CONCLUSIONS: Our data confirm that MCC
      deficiency, despite low penetrance, may lead to a severe clinical phenotype
      resembling classical organic acidurias. However, neither the genotype nor the
      biochemical phenotype is helpful in predicting the clinical course.

PMID- 22642866
TI  - Use of darbepoetin alfa in European clinical practice for the management of
      chemotherapy-induced anaemia in four tumour types: final data from the CHOICE
      study.
AB  - OBJECTIVES: The CHOICE study was a prospective, multicentre, observational study
      designed to assess levels of adherence in current clinical practice to the
      European product label and EORTC guidelines for the treatment of chemotherapy
      induced anaemia (CIA) with darbepoetin alfa (DA). Here we present data split by
      tumour types: breast, colorectal, ovarian and lung. METHODS: Haemoglobin (Hb)
      levels and red blood cell transfusion requirements were evaluated among patients
      with solid tumours in 11 European countries. The primary outcome measure was the
      proportion of patients with a target Hb level of >=10-<=12 g/dL. RESULTS: The
      full analysis set included 1887 patients (mean +/- SD 62.4 +/- 11.4 years); 1585
      (84%) had a current disease stage of >=3. Common chemotherapy regimens were non
      platinum + non-taxane based (n = 696 [37%]) or platinum + non-taxane based (n =
      660 [35%]). Breast cancer (n = 575): The mean +/- SD Hb level at baseline was 9.9
      +/- 0.8 g/dL (n = 568). Target Hb level was reached by 187 (55%) patients.
      Colorectal cancer (n = 310): At baseline the mean +/- SD Hb level was 9.8 +/- 0.8
      g/dL (n = 306). Target Hb level was reached by 107 patients (56%). Ovarian cancer
      (n = 301): The mean +/- SD Hb level at baseline was 9.7 +/- 0.8 g/dL (n = 294).
      Target Hb level was reached by 81 patients (44%). Lung cancer (n = 701): At
      baseline the mean +/- SD Hb level was 9.8 +/- 0.9 g/dL (n = 692). Target Hb level
      was reached by 142 patients (39%). SAFETY: Five severe or life-threatening
      adverse drug reactions were seen (three patients with breast cancer, one patient
      with colorectal cancer and one patient with ovarian cancer). LIMITATIONS:
      Potential bias could not be excluded due to the study's observational nature.
      CONCLUSIONS: This study demonstrates that the recommendations are adhered to in
      clinical practice, with the mean starting Hb level <10 g/dL irrespective of
      tumour type. Furthermore, DA is likely to be effective and well tolerated for the
      treatment of CIA in patients with breast, colorectal, ovarian or lung cancer.

PMID- 22642867
TI  - A final analysis from the CHOICE study examining darbepoetin alfa use for
      chemotherapy-induced anaemia in current European clinical practice.
AB  - OBJECTIVES: The CHOICE study was a prospective, multicentre, observational study
      designed to assess the level of adherence in current clinical practice to the
      European product label and the EORTC guidelines for the treatment of chemotherapy
      induced anaemia with darbepoetin alfa (DA). METHODS: Hb levels and red blood cell
      (RBC) transfusion requirements were evaluated among 1900 patients with solid
      tumours in 11 European countries. The primary outcome measure was the proportion
      of patients with a target Hb level of >=10-<=12 g/dL after 9 weeks' DA treatment.
      RESULTS: The full analysis set (FAS) comprised 1887 patients (mean +/- SD age
      62.4 +/- 11.4 years) divided into categories by baseline Hb < 9 g/dL (n = 281); 9
      <10 g/dL (n = 770); 10-<11 g/dL (n = 695); >=11 g/dL (n = 114). The proportion of
      patients who remained on the study at week 9 achieving the target Hb level was
      37% (n = 60), 48% (n = 217), 54% (n = 210) and 38% (n = 23) in the subgroups with
      a baseline Hb level of <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and >=11 g/dL,
      respectively. In the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and >=11 g/dL subgroups of
      the FAS, the number of patients maintaining Hb levels >=10 g/dL after their first
      achievement of an Hb value of 10 g/dL was 95 (34%), 372 (48%), 476 (68%) and 87
      (76%), respectively. The Kaplan-Meier percentages of patients who required an RBC
      transfusion from week 5 until end of treatment period were: 29%, 20%, 12% and 17%
      in the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and >=11 g/dL subgroups, respectively.
      Kaplan-Meier percentages of patients reaching an Hb level of >13 g/dL were 10%,
      9%, 21% and 29%, respectively. Potential bias could not be excluded due to the
      study's observational nature. CONCLUSIONS: DA initiation and target Hb ranges
      adhered to current guidelines in the majority of patients. Furthermore, this
      study demonstrates faster achievement of the target range and reduced transfusion
      requirements are associated with initiation of DA at Hb levels of 9-<10 g/dL and
      10-<11 g/dL rather than <9 g/dL.

PMID- 22642868
TI  - Molecular characterization of tripartite motif protein 25 (TRIM25) involved in
      ERalpha-mediated transcription in the Korean rose bitterling Rhodeus uyekii.
AB  - Tripartite motif-containing 25 (TRIM25), also known as estrogen-responsive finger
      protein (EFP), plays an essential role in cell proliferation and innate immunity.
      In the present study, we isolated and characterized the TRIM25 cDNA of the Korean
      rose bitterling Rhodeus uyekii, designated RuTRIM25. It encodes an open reading
      frame of 669 amino acids containing an N-terminal RBCC motif composed of a RING
      domain, two B boxes, and a coiled-coil domain and a C-terminal B30.2 (PRY/SPRY)
      domain. RuTRIM25 shows strong homology (79.7%) to zebrafish TRIM25 and shared
      32.4-28.8% homology with TRIM25 from other species, including mammals. RuTRIM25
      mRNA was expressed ubiquitously. It was highly expressed in the ovary, spleen,
      and liver and moderately in the stomach and intestine of normal Korean rose
      bitterling. The intracellular localization of RuTRIM25 in HEK293T cells was
      diffusely localized in the cytoplasm and its RING domain deletion mutant
      (RuTRIM25DeltaR) was detected diffusely with some aggregates in the cytoplasm.
      RuTRIM25, but not RuTRIM25DeltaR, is ubiquitinated in vivo. Ectopic expression of
      RuTRIM25 synergistically activated the estrogen receptor (ER)-mediated luciferase
      reporter activity in a dose-dependent manner in HEK293T cells. Together, these
      results suggest that the RuTRIM25 regulates the ER-mediated transcription in fish
      similarly to its mammalian counterpart.

PMID- 22642869
TI  - Differentiation of refined and virgin edible oils by means of the trans- and cis
      phytol isomer distribution.
AB  - The differentiation of nonrefined (e.g., cold-pressed) and refined edible oils is
      an important task in food control because of the higher commercial value of the
      former. Here, we explored the suitability of the relative abundance of cis-phytol
      as a marker for authentication of nonrefined edible oils. Phytol, the tetramethyl
      branched, monoenoic alcohol, is found widespread in nature as a part of
      chlorophyll. In chlorophyll, only trans-phytol is found. In this study, we
      present a method for the analysis of the phytol isomers, considering that traces
      of cis-phytol (contributing 0.1% to the phytol content) can be determined next to
      trans-phytol. For this purpose, phytol was gathered with the unsaponifiable
      matter from the oil, trimethylsilylated, and analyzed by gas chromatography
      coupled to mass spectrometry. With this method, 27 samples of edible oils (16
      refined and 11 nonrefined edible oils) were analyzed for the abundance of cis
      phytol relative to trans-phytol. In the nonrefined oils (e.g., olive oil,
      rapeseed oil, maize oil, and sunflower oil), cis-phytol contributed 0.1% (n = 3)
      or less (n = 8) to the phytol content. In contrast, the refined olive oils (n =
      4) contained a share of 1.3-3% cis-phytol; the refined rapeseed oil (n = 3)
      contained a share of 0.7-1.0% cis-phytol; and the refined sunflower oil (n = 4)
      contained a share of 0.3-0.9% cis-phytol. Only one refined pomegranate kernel did
      not contain cis-phytol. The phytol concentration was not suited to distinguish
      nonrefined from refined oils. In contrast, our data suggest that the virtual
      absence of cis-phytol can be used as a marker for nonrefined (e.g., cold-pressed)
      edible oils.

PMID- 22642870
TI  - Combined preoperative onyx embolization and protective internal carotid artery
      covered stent placement for treatment of glomus vagale tumor: review of
      literature and illustrative case.
AB  - OBJECTIVE: Surgical resection of complex glomus vagale tumors can be complicated
      by extensive blood loss and might require surgical sacrifice of an encased
      internal carotid artery. METHODS: A young patient presented with mass effect from
      glomus valage tumor. Computerized  tomography angiography showed an encased
      internal carotid artery. Cerebral angiography demonstrated a highly vascular
      tumor. A literature review was performed for endovascular treatment options for
      neck tumors. RESULTS: Staged preoperative embolization of feeder arteries via
      internal  maxillary artery, and thyrocervical trunk with onyx was performed. A
      covered stent was implanted in the cervical internal carotid artery to the common
      carotid artery; this resulted in complete devascularization of the tumor with
      exclusion of external carotid artery from the circulation. This  is followed by
      surgical resection of the tumor. CONCLUSION: Preoperative embolization with onyx
      decreased the amount of blood loss intra-operatively. The implantation of a
      covered stent in the cervical internal carotid artery through the common carotid
      artery contributed for further  devasculatization of the tumor bed, as well as
      provided a lumen continuity in case iatrogenic carotid injury is encountered
      intra-operatively.

PMID- 22642871
TI  - Cytokines and olfactory bulb microglia in response to bacterial challenge in the
      compromised primary olfactory pathway.
AB  - BACKGROUND: The primary olfactory pathway is a potential route through which
      microorganisms from the periphery could potentially access the central nervous
      system. Our previous studies demonstrated that if the olfactory epithelium was
      damaged, bacteria administered into the nasal cavity induced nitric oxide
      production in olfactory ensheathing cells. This study investigates the cytokine
      profile of olfactory tissues as a consequence of bacterial challenge and
      establishes whether or not the bacteria are able to reach the olfactory bulb in
      the central nervous system. METHODS: The olfactory epithelium of C57BL/6 mice was
      damaged by unilateral Triton X-100 nasal washing, and Staphylococcus aureus was
      administered ipsilaterally 4 days later. Olfactory mucosa and bulb were harvested
      6 h, 24 h and 5 days after inoculation and their cytokine profile compared to
      control tissues. The fate of S. aureus and the response of bulbar microglia were
      examined using fluorescence microscopy and transmission electron microscopy.
      RESULTS: In the olfactory mucosa, administered S. aureus was present in
      supporting cells of the olfactory epithelium, and macrophages and olfactory nerve
      bundles in the lamina propria. Fluorescein isothiocyanate-conjugated S. aureus
      was observed within the olfactory mucosa and bulb 6 h after inoculation, but
      remained restricted to the peripheral layers up to 5 days later. At the 24-h time
      point, the level of interleukin-6 (IL-6) and tumour necrosis factor-alpha in the
      compromised olfactory tissues challenged with bacteria (12,466 +/- 956 pg/ml and
      552 +/- 193 pg/ml, respectively) was significantly higher than that in
      compromised olfactory tissues alone (6,092 +/- 1,403 pg/ml and 80 +/- 2 pg/ml,
      respectively). Immunohistochemistry confirmed that IL-6 was present in several
      cell types including olfactory ensheathing cells and mitral cells of the
      olfactory bulb. Concurrently, there was a 4.4-, 4.5- and 2.8-fold increase in the
      density of iNOS-expressing cells in the olfactory mucosa, olfactory nerve and
      glomerular layers combined, and granule layer of the olfactory bulb,
      respectively. CONCLUSIONS: Bacteria are able to penetrate the immunological
      defence of the compromised olfactory mucosa and infiltrate the olfactory bulb
      within 6 h even though a proinflammatory profile is mounted. Activated microglia
      may have a role in restricting bacteria to the outer layers of the olfactory
      bulb.

PMID- 22642872
TI  - Molecular characterization of fungal populations on the tongue dorsum of
      institutionalized elderly adults.
AB  - OBJECTIVES: To characterize the global composition of oral fungal populations in
      frail elderly adults and to investigate the relationship with their health
      status. MATERIALS AND METHODS: We investigated the fungal populations on the
      tongue dorsum in 291 institutionalized elderly adults by molecular PCR-based
      techniques using internal transcribed spacer regions of nuclear ribosomal DNA.
      RESULTS: Quantitative PCR analysis showed that fungi were present on the tongue
      dorsum of 128 subjects at >=10(4)  CFU per sample, and 35 of them exceeded 10(5) 
      CFU per sample. Length heterogeneity-PCR analysis and nucleotide sequence
      determinations showed that Candida albicans was most frequently detected in those
      subjects with fungi at >=10(4)  CFU per sample (105 subjects), followed by
      Candida dubliniensis (78), Malassezia restricta (57), and Candida tropicalis
      (45). Statistical analysis revealed that those subjects with >=10(5)  CFU of
      fungi other than C. albicans per sample had an increased risk of fever (>=7
      febrile days per 12 months) compared with subjects with <10(5)  CFU per sample,
      after adjustment for other fever-associated confounding factors. CONCLUSIONS:
      These data demonstrate that the oral cavity of the elderly is inhabited by a
      diverse array of fungi not limited to typical Candida species and they suggest
      that the diversity in distribution is associated with health status.

PMID- 22642873
TI  - Hepatic vitamin A preloading reduces colorectal cancer metastatic multiplicity in
      a mouse xenograft model.
AB  - Previous research in our laboratory showed that retinol inhibited all-trans
      retinoic acid (ATRA)-resistant human colon cancer cell invasion via a retinoic
      acid receptor-independent mechanism in vitro. The objective of the current study
      was to determine if dietary vitamin A supplementation inhibited metastasis of
      ATRA-resistant colon cancer cells in a nude mouse xenograft model. Female nude
      mice (BALB/cAnNCr-nu/nu, n = 14 per group) consumed a control diet (2,400 IU
      retinyl palmitate/kg diet) or a vitamin A supplemented diet (200,000 IU retinyl
      palmitate/kg diet) for 1 mo prior to tumor cell injection to preload the liver
      with vitamin A. HCT-116, ATRA-resistant, human colon cancer cells were
      intrasplenically injected. Mice continued to consume their respective diets for 5
      wk following surgery. Consumption of supplemental vitamin A decreased hepatic
      metastatic multiplicity to 17% of control. Hepatic and splenic retinol and
      retinyl ester concentrations were significantly higher in the mice supplemented
      with vitamin A when compared to mice consuming the control diet. Supplemental
      vitamin A did not decrease body weight, feed intake, or cause toxicity. Thus,
      supplemental dietary vitamin A may decrease the overall number of hepatic
      metastasis resulting from colon cancer.

PMID- 22642874
TI  - Self-healing fish gelatin/sodium montmorillonite biohybrid coacervates:
      structural and rheological characterization.
AB  - Complex coacervation driven by associative electrostatic interactions was studied
      in mixtures of exfoliated sodium-montmorillonite (Na(+)-MMT) nanoplatelets and
      fish gelatin, at a specific mixing ratio and room temperature. Structural and
      viscoelastic properties of the coacervate phase were investigated as a function
      of pH by means of different complementary techniques. Independent of the
      technique used, the results consistently showed that there is an optimum pH value
      at which the coacervate phase shows the tightest structure with highest
      elasticity. The solid-like coacervates showed an obvious shear-thinning behavior
      and network fracture but immediately recovered back into their original elastic
      character upon removal of the shear strain. The nonlinear mechanical response
      characterized by single step stress relaxation experiments revealed the same
      trend for the yield stress and isochronal shear modulus of the coacervates as a
      function of pH with a maximum at pH 3.0 and lower values at 2.5 and 3.5 pHs,
      followed by a very sharp drop at pH 4.0. Finally, small-angle X-ray scattering
      (SAXS) data confirmed that at pHs lower than 4.0 the coacervate phases were dense
      and structured with a characteristic length scale (xi(SAXS)) of ~7-9 nm.
      Comparing the xi(SAXS) with rheological characteristic length (xi(rheol))
      estimated from low-frequency linear viscoelastic data and network theory, it was
      concluded that both the strength of the electrostatic interactions and the
      conformation of the gelatin chains before and during of the coacervation process
      are responsible for the structure and rigidity of the coacervates.

PMID- 22642875
TI  - Evidence for a free troposphere source of mercury in wet deposition in the
      Western United States.
AB  - Mercury (Hg) in wet deposition in the United States is measured as part of the
      National Atmospheric Deposition Program--Hg Deposition Network (MDN). This study
      focused on compiling and assessing data collected since 2003 at two sites in
      Nevada, and at one in Nevada and three in Idaho where data were collected over
      shorter time intervals. At all locations the highest volume weighted
      concentrations and deposition were observed in the summer, a time of low
      precipitation, but high gaseous oxidized Hg (GOM) concentrations. Detailed
      assessment of high Hg wet deposition events showed variability across the region
      and higher deposition at the higher elevation sites. Potential Source
      Contribution Function analyses showed no specific point sources associated with
      the high Hg wet deposition events, but air masses derived predominantly from the
      southwest. Although this region has potential local and regional sources of GOM,
      detailed back trajectory analyses, the environmental setting of Nevada, results
      from other studies in Nevada, and GEOS-Chem modeling results point toward a free
      troposphere contribution to mercury in wet deposition input to this area of the
      western United States.

PMID- 22642876
TI  - Prevalence and significance of anaemia in patients receiving long-course
      neoadjuvant chemoradiotherapy for rectal carcinoma.
AB  - AIM: The study aimed to assess the prevalence and significance of anaemia during
      long-course neoadjuvant radiotherapy for rectal cancer at our centre. METHOD:
      Hospital coding and a prospective oncology database were used to identify all
      patients undergoing long-course neoadjuvant radiotherapy for rectal cancer at our
      centre between 2004 and 2009. A retrospective review of computerized records was
      used to extract individual patient data. Anaemia was defined as a haemoglobin
      level of < 11.5 g/dl for women and of < 13 g/dl for men. Downstaging was assessed
      by comparing radiological stage (rTNM) with histological stage (ypTNM). Tumour
      regression after radiotherapy was assessed using the Rectal Cancer Regression
      Group (RCRG) scores of 1-3. The results were analysed using Gnu PSPP statistical
      software. RESULTS: There were 70 patients (51 men) of median age 66
      (interquartile range 60-72.75) years. Of these, 24 were anaemic. Two (3%) had no
      haemoglobin level recorded and were excluded. Forty-two per cent of anaemic
      patients demonstrated mural (T) downstaging compared with 68% of nonanaemic
      patients (P = 0.03). There was no difference in nodal downstaging between the
      groups. The RCRG scores showed more tumour regression in nonanaemic patients than
      in anaemic patients, as follows: RCRG 1, 59%vs 30%; RCRG 2, 11%vs 17%; and RCRG
      3, 38%vs 46% (P < 0.001). CONCLUSION: The prevalence of anaemia in patients
      undergoing long-course neoadjuvant radiotherapy was 35%. Anaemia during long
      course neoadjuvant radiotherapy was associated with significant reductions in
      tumour downstaging and regression.

PMID- 22642878
TI  - Perimenstrual symptoms and symptoms at midlife in Puebla, Mexico.
AB  - OBJECTIVES: To examine perimenstrual symptoms in relation to hot flushes and
      depressive symptoms among 755 pre- and postmenopausal women aged 40-60 years
      drawn from a general population in Puebla, Mexico. METHODS: Hot flushes and
      depressed mood during the past 2 weeks were queried, along with cramps and other
      symptoms experienced during or before menstruation. Relationships among
      perimenstrual symptoms were examined by factor analyses. Logistic regression was
      used to assess determinants of hot flushes and determinants of depressed mood at
      midlife. RESULTS: Fifty-four percent of the women reported abdominal cramping
      (colicos) during menstruation; fewer reported irritability (8%) and depressed
      mood (9%). Gastrointestinal complaints were most frequently volunteered (12%),
      followed by breast tenderness (10%) and mid-back pain (9%). Emotional symptoms
      clustered separately from perimenstrual symptoms. In bivariate analyses,
      abdominal cramping and waist pain were associated with hot flushes at midlife (p
      <0.01) and remained significant determinants after controlling for potential
      confounders. Depressed mood with menstruation was associated with depressed mood
      at midlife (p <0.05). After controlling for education, socioeconomic status and
      parity, perimenstrual irritability and depressed mood raised the risk of midlife
      depressed mood, although significance was lost after adding current hot flushes
      and trouble sleeping. CONCLUSIONS: The relationship between abdominal cramps and
      hot flushes may be hormonal or sociocultural. The lack of association between
      depressed mood with menstruation and depressed mood at midlife after controlling
      for current hot flushes and trouble sleeping suggests that concurrent
      difficulties were more important than past history of depression in this
      population.

PMID- 22642877
TI  - Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin
      paclitaxel therapy.
AB  - BACKGROUND: Advanced ovarian cancer is treated with cytoreductive surgery and
      combination platinum- and taxane-based chemotherapy. Although most patients have
      acute clinical response to this strategy, the disease ultimately recurs. In this
      work we questioned whether the synthetic steroid mifepristone, which as
      monotherapy inhibits the growth of ovarian cancer cells, is capable of preventing
      repopulation of ovarian cancer cells if given after a round of lethal cisplatin
      paclitaxel combination treatment. METHODS: We established an in vitro approach
      wherein ovarian cancer cells with various sensitivities to cisplatin or
      paclitaxel were exposed to a round of lethal doses of cisplatin for 1 h plus
      paclitaxel for 3 h. Thereafter, cells were maintained in media with or without
      mifepristone, and short- and long-term cytotoxicity was assessed. RESULTS: Four
      days after treatment the lethality of cisplatin-paclitaxel was evidenced by
      reduced number of cells, increased hypodiploid DNA content, morphological
      features of apoptosis, DNA fragmentation, and cleavage of caspase-3, and of its
      downstream substrate PARP. Short-term presence of mifepristone either enhanced or
      did not modify such acute lethality. Seven days after receiving cisplatin
      paclitaxel, cultures showed signs of relapse with escaping colonies that
      repopulated the plate in a time-dependent manner. Conversely, cultures exposed to
      cisplatin-paclitaxel followed by mifepristone not only did not display signs of
      repopulation following initial chemotherapy, but they also had their clonogenic
      capacity drastically reduced when compared to cells repopulating after cisplatin
      paclitaxel. CONCLUSIONS: Cytostatic concentrations of mifepristone after exposure
      to lethal doses of cisplatin and paclitaxel in combination blocks repopulation of
      remnant cells surviving and escaping the cytotoxic drugs.

PMID- 22642879
TI  - Elevated serum leptin levels in patients with acute myocardial infarction;
      correlation with coronary angiographic and echocardiographic findings.
AB  - BACKGROUND: To assess the relationship between serial serum leptin levels in
      patients with acute myocardial infarction (AMI) who received thrombolysis and the
      degree of coronary atherosclerosis, coronary reperfusion, echocardiographic
      findings, and clinical outcome. 51 consecutive patients presenting with AMI were
      studied. Clinical characteristics including age, sex, body mass index (BMI) and
      cardiovascular risk factors were recorded. Serial serum leptin levels at the time
      of admission and subsequently at 0, 6, 12, 24, 36, 60 hours afterwards were
      obtained. Coronary angiography was performed in 34 patients; the relation between
      serum leptin levels and evidence of coronary reperfusion as well as the extent of
      coronary atherosclerosis according to the coronary artery surgery study
      classification (CASS) were evaluated. Echocardiographic evaluation was performed
      in all patients. 36 matched patients were enrolled as control group who had serum
      leptin level 9.4 +/- 6.5 ng/ml. RESULTS: The patients mean age was 50.5 +/- 10.6
      years. There were 47 males and 3 females. 37.1% were diabetics, 23.5% were
      hypertensive, 21.6% were dyslipidemic and 22.7% were obese (BMI >= 30). Leptin
      concentrations (ng/ml) increased and peaked at the 4th sample (36 hrs) after
      admission (mean +/- SD) sample (1) =9.55 +/- 7.4, sample (2) =12.9 +/- 8.4,
      sample (3) =13.8 +/- 10.4, sample (4) =18.9 +/- 18.1, sample (5) =11.4 +/- 6.5,
      sample (6) =10.8 +/- 8.9 ng/ml. There was a significant correlation between serum
      leptin and BMI (r = 0.342; p = 0.03). Leptin levels correlated significantly to
      creatine kinase level on the second day (r = 0.43, p <= 0.01). Significant
      correlation of mean serum leptin with the ejection fraction (P < 0.05) was found.
      No difference in timing of peak serum leptin between patients who achieved
      coronary reperfusion vs. those who did not (p = 0.8). There was a trend for an
      increase in the mean serum leptin levels with increasing number of diseased
      vessels. There was no correlation between serum leptin levels and outcome neither
      during the hospitalization nor at 9 months follow up. CONCLUSION: Serum leptin
      levels increase after myocardial infarction. Serum leptin level may be a
      predictor of the left ventricular ejection fraction and the degree of
      atherosclerosis but not of coronary reperfusion.

PMID- 22642881
TI  - Hydrophobic interaction network analysis for thermostabilization of a mesophilic
      xylanase.
AB  - One widely known drawback of enzymes is their instability in diverse conditions.
      The thermostability of enzymes is particularly relevant for industrial
      applications because operation at high temperatures has the advantage of a faster
      reaction rate. Protein stability is mainly determined in this study by intra
      molecular hydrophobic interactions that have a collective and 3-dimensional
      clustering effect. To interpret the thermostability of enzymes, network analysis
      was introduced into the protein structure, and a network parameter of structural
      hierarchy, k of k-clique, was used to discern more developed hydrophobic
      interaction clusters in the protein structure. The favorable clustering
      conformations of hydrophobic residues, which seemed to be important for protein
      thermostability, were discovered by the application of a network analysis to
      hydrophobic interactions of GH11 xylanases. Coordinating higher k-clique
      hydrophobic interaction clusters through the site-directed mutagenesis of the
      model enzyme, Bacillus circulans xylanase, stabilized the local structure and
      thus improved thermostability, such that the enzyme half-life and melting
      temperature increased by 78 fold and 8.8  degrees C, respectively. This study
      highlights the advantages of interpreting collective hydrophobic interaction
      patterns and their structural hierarchy and the possibility of applying network
      analysis to the thermostabilization of enzymes.

PMID- 22642882
TI  - The importance of considering all attributes of memory in behavioral
      endophenotyping of mouse models of genetic disease.
AB  - In order to overcome difficulties in evaluating cognitive function in mouse
      models of genetic disorders, it is critical to take into account the background
      strain of the mouse and reported phenotypes in the clinical population being
      studied. Recent studies have evaluated cognitive function across a number of
      background strains and found that spatial memory assayed by the water maze and
      contextual fear conditioning often does not provide optimal results. The logical
      extension to these results is to emphasize not only spatial, but all attributes
      or domains of memory function in behavioral phenotyping experiments. A careful
      evaluation of spatial, temporal, sensory/perceptual, affective, response,
      executive, proto-linguistic, and social behaviors designed to specifically
      evaluate the cognitive function each mouse model can be performed in a rapid,
      relatively high throughput manner. Such results would not only provide a more
      comprehensive snapshot of brain function in mouse disease models than the more
      common approach that approaches nonspecific spatial memory tasks to evaluate
      cognition, but also would better model the disorders being studied.

PMID- 22642883
TI  - The role of adult hippocampal neurogenesis in reducing interference.
AB  - Adult neurogenesis in the hippocampal dentate gyrus plays an important role in
      learning and memory. However, the precise contribution of the new neurons to
      hippocampal function remains controversial. Emerging evidence suggests that
      neurogenesis is important for pattern separation and for mitigating interference
      when similar items must be learned at different times. In the present study, we
      directly test this prediction using a recently developed olfactory memory task
      that has those specific features. In this task, rats learn two highly interfering
      lists of odor pairs, one after the other, in either the same or in different
      contexts. Consistent with our hypothesis, focal cranial irradiation, resulting in
      selective reduction of neurogenesis within the dentate gyrus, significantly
      impaired the ability to overcome interference during learning of the second list.
      The ability to learn a single odor list was unimpaired. We also show that
      irradiation had no effect on learning in a hippocampal-dependent spatial
      alternation task. Although both tasks involved learning interfering responses,
      the time course for learning the interfering items differed. Learning the
      interfering odor lists took place sequentially, over the course of several
      sessions, whereas learning the interfering spatial locations took place
      concurrently, within each session. Thus, the gradual addition of new neurons may
      have provided a pattern separation mechanism for the olfactory task but not for
      the maze task. These findings demonstrate a role for neurogenesis in resolving
      interference and they are consistent with models suggesting a critical role for
      neurogenesis in pattern separation.

PMID- 22642880
TI  - Suggested guidelines for the diagnosis and management of urea cycle disorders.
AB  - Urea cycle disorders (UCDs) are inborn errors of ammonia detoxification/arginine
      synthesis due to defects affecting the catalysts of the Krebs-Henseleit cycle
      (five core enzymes, one activating enzyme and one mitochondrial
      ornithine/citrulline antiporter) with an estimated incidence of 1:8.000. Patients
      present with hyperammonemia either shortly after birth (~50%) or, later at any
      age, leading to death or to severe neurological handicap in many survivors.
      Despite the existence of effective therapy with alternative pathway therapy and
      liver transplantation, outcomes remain poor. This may be related to
      underrecognition and delayed diagnosis due to the nonspecific clinical
      presentation and insufficient awareness of health care professionals because of
      disease rarity. These guidelines aim at providing a trans-European consensus to:
      guide practitioners, set standards of care and help awareness campaigns. To
      achieve these goals, the guidelines were developed using a Delphi methodology, by
      having professionals on UCDs across seven European countries to gather all the
      existing evidence, score it according to the SIGN evidence level system and draw
      a series of statements supported by an associated level of evidence. The
      guidelines were revised by external specialist consultants, unrelated authorities
      in the field of UCDs and practicing pediatricians in training. Although the
      evidence degree did hardly ever exceed level C (evidence from non-analytical
      studies like case reports and series), it was sufficient to guide practice on
      both acute and chronic presentations, address diagnosis, management, monitoring,
      outcomes, and psychosocial and ethical issues. Also, it identified knowledge
      voids that must be filled by future research. We believe these guidelines will
      help to: harmonise practice, set common standards and spread good practices with
      a positive impact on the outcomes of UCD patients.

PMID- 22642885
TI  - Appetitive-aversive interactions in Pavlovian fear conditioning.
AB  - The existence of value coding and salience coding neurons in the mammalian brain,
      including in habenula and ventral tegmental area, has sparked considerable
      interest in the interactions that occur between Pavlovian appetitive and aversive
      conditioning. Here we studied these appetitive-aversive interactions at the
      behavioral level by assessing the learning that occurs when a Pavlovian
      appetitive conditioned stimulus (conditional stimulus, CS) serves as a CS for
      shock in Pavlovian fear conditioning. A Pavlovian appetitive CS was retarded in
      the rate at which it could be transformed into a fear CS (counterconditioning),
      but the presence of the appetitive CS augmented fear learning to a concurrently
      presented neutral CS (superconditioning). Retardation of fear learning was not
      alleviated by manipulations designed to restore the associability of the
      appetitive CS before fear conditioning but was alleviated by manipulations
      designed to increase the aversive quality of the shock unconditioned stimulus
      (US). These findings are consistent with opponent interactions between the
      appetitive and aversive motivational systems and provide a behavioral approach
      for assessing the neural correlates of these appetitive-aversive interactions.

PMID- 22642884
TI  - Effects of neonatal amygdala lesions on fear learning, conditioned inhibition,
      and extinction in adult macaques.
AB  - Fear conditioning studies have demonstrated the critical role played by the
      amygdala in emotion processing. Although all lesion studies until now
      investigated the effect of adult-onset damage on fear conditioning, the current
      study assessed fear-learning abilities, as measured by fear-potentiated startle,
      in adult monkeys that had received neonatal neurotoxic amygdala damage or sham
      operations. After fear acquisition, their abilities to learn and use a safety cue
      to modulate their fear to the conditioned cue, and, finally, to extinguish their
      response to the fear conditioned cue were measured with the AX+/BX- Paradigm.
      Neonatal amygdala damage retarded, but did not completely abolish, the
      acquisition of a learned fear. After acquisition of the fear signal, four of the
      six animals with neonatal amygdala lesions discriminated between the fear and
      safety cues and were also able to use the safety signal to reduce the potentiated
      startle response and to extinguish the fear response when the air-blast was
      absent. In conclusion, the present results support the critical contribution of
      the amygdala during the early phases of fear conditioning that leads to quick,
      robust responses to potentially threatening stimuli, a highly adaptive process
      across all species and likely to be present in early infancy. The neonatal
      amygdala lesions also indicated the presence of amygdala-independent alternate
      pathways that are capable to support fear learning in the absence of a functional
      amygdala. This parallel processing of fear responses within these alternate
      pathways was also sufficient to support the ability to flexibly modulate the
      magnitude of the fear responses.

PMID- 22642886
TI  - Chemosensory cue conditioning with stimulants in a Caenorhabditis elegans animal
      model of addiction.
AB  - The underlying molecular mechanisms of drug abuse and addiction behaviors are
      poorly understood. Caenorhabditis elegans (C. elegans) provide a simple, whole
      animal model with conserved molecular pathways well suited for studying the
      foundations of complex diseases. Historically, chemotaxis has been a measure used
      to examine sensory approach and avoidance behavior in worms. Chemotaxis can be
      modulated by previous experience, and cue-dependent conditioned learning has been
      demonstrated in C. elegans, but such conditioning with drugs of abuse has not
      been reported. Here we show that pairing a distinctive salt cue with a drug
      (cocaine or methamphetamine) results in a concentration-dependent change in
      preference for the cue that was paired with the drug during conditioning.
      Further, we demonstrate that pairing of either drug with a distinctive food type
      can also increase preference for the drug-paired food in the absence of the drug.
      Dopamine-deficient mutants did not develop drug-paired, cue-conditioned
      responses. The findings suggest that, like vertebrates, C. elegans display a
      conditioned preference for environments containing cues previously associated
      with drugs of abuse, and this response is dependent on dopamine
      neurotransmission. This model provides a new and powerful method to study the
      genetic and molecular mechanisms that mediate drug preference.

PMID- 22642887
TI  - Sex differences in object-in-place memory of adult rats.
AB  - Male rodents typically display an advantage over female conspecifics in tasks
      that assess memory for the identity or location of objects. However, the
      performance of female rodents on object recognition and object location tasks
      often is enhanced by elevated levels of ovarian steroids. The novel object-in
      place task, combines elements of object recognition and object location tasks
      used to assess rodent object memory. Until now, only male rats have been tested
      on the object-in-place task, therefore, a study was conducted to compare the
      performance of males to females under different hormone conditions. Rats were
      given a sample phase to study the locations of four objects in an open field.
      After various delays, a test phase was administered with the locations of two
      objects reversed. Increased investigation of moved objects indicates memory for
      these objects and their original locations. Rats were able to discriminate moved
      from unmoved objects after a brief 5-min delay, regardless of biological sex or
      hormone status. However, gonadally intact males, but not diestrous females, were
      able to discriminate object locations after a 30-min delay. In contrast,
      ovariectomized females treated with estradiol and progesterone discriminated
      moved from unmoved objects after a 60-min delay while ovariectomized vehicle
      treated females and gonadally intact males did not. Results indicate that female
      rats outperform males on a memory task that combines object recognition and
      location but only when circulating levels of the ovarian steroids, estradiol and
      progesterone, are elevated and only when memory is challenged by an extended
      retention interval.

PMID- 22642888
TI  - Direct measurement of spontaneous strategy selection in a virtual Morris water
      maze shows females choose an allocentric strategy at least as often as males do.
AB  - Considerable evidence indicates that males navigate large-scale space better than
      females, and some have previously attributed this difference to a greater ability
      of males to select or use an allocentric (cognitive mapping) navigational
      strategy. We directly tested this proposal by having males and females navigate
      in an "ambiguous" virtual Morris water maze environment that permitted
      participants to choose and use either an allocentric or an egocentric strategy. A
      novel probe trial at the end of training revealed which strategy each participant
      had been using and showed that the strategy selected by the greatest number of
      males and females was allocentric, and that this bias was even greater for
      females. Traditional measures of navigational performance (distance, latency,
      probe dwell time) indicated that overall, males were more efficient than females.
      However, this gender difference was not related to strategy choice: males were
      better than females regardless of strategy, though the difference was significant
      only in those navigating allocentrically. These data indicate that while males
      may navigate allocentrically more efficiently than females, this does not account
      for the male advantage in navigation. The data also indicate that under specific
      circumstances, females may also prefer and use an allocentric strategy to
      navigate. These findings have implications for theories regarding the
      differential use of the hippocampus by men and women.

PMID- 22642889
TI  - Early cognitive dysfunction in the HD 51 CAG transgenic rat model of Huntington's
      disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder in humans caused by an
      expansion of a CAG trinucleotide repeat that produces choreic movements, which
      are preceded by cognitive deficits. The HD transgenic rat (tgHD), which contains
      the human HD mutation with a 51 CAG repeat allele, exhibits motor deficits that
      begin when these rats are 12 months of age. However, there are no reports of
      cognitive dysfunction occurring prior to this. To assess whether cognitive
      dysfunction might precede motor deficits in tgHD rats, one group of 9-month-old
      male rats with homozygotic mutated genes and one group of wild-type (WT) rats
      underwent three testing phases in a unique Spatial Operant Reversal Test (SORT)
      paradigm, as well as assessment of spontaneous motor activity. After testing,
      morphological and histological examination of the brains were made. Results
      indicated that tgHD rats acquired the cued-response (Phase 1) portion of the
      SORT, but made significantly more errors during the reversal (Phase 2) and during
      the pseudorandomized reversals (Phase 3) portion of the study, when compared to
      WT rats. Analysis of the data using mathematical principles of reinforcement
      revealed no memory, motor, or motivational deficits. These results indicate that
      early cognitive dysfunction, as measured by the SORT, occur prior to motor
      deficits, gross anatomical changes, or cell loss in the tgHD rat with 51 CAG
      repeats, and suggest that this protocol could provide a useful screen for
      therapeutic studies.

PMID- 22642890
TI  - Enhanced appetitive learning and reversal learning in a mouse model for Prader
      Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is caused by lack of paternally derived gene
      expression from the imprinted gene cluster on human chromosome 15q11-q13. PWS is
      characterized by severe hypotonia, a failure to thrive in infancy and, on
      emerging from infancy, evidence of learning disabilities and overeating behavior
      due to an abnormal satiety response and increased motivation by food. We have
      previously shown that an imprinting center deletion mouse model (PWS-IC) is
      quicker to acquire a preference for, and consume more of a palatable food. Here
      we examined how the use of this palatable food as a reinforcer influences
      learning in PWS-IC mice performing a simple appetitive learning task. On a
      nonspatial maze-based task, PWS-IC mice acquired criteria much quicker, making
      fewer errors during initial acquisition and also reversal learning. A
      manipulation where the reinforcer was devalued impaired wild-type performance but
      had no effect on PWS-IC mice. This suggests that increased motivation for the
      reinforcer in PWS-IC mice may underlie their enhanced learning. This supports
      previous findings in PWS patients and is the first behavioral study of an animal
      model of PWS in which the motivation of behavior by food rewards has been
      examined.

PMID- 22642891
TI  - Subcortical motor circuit excitability during simple and choice reaction time.
AB  - The purpose of the current study was to examine the relationship between movement
      preparation and excitability of subcortical motor circuits, as measured by the
      reflexive response to a startling acoustic stimulus. We compared the size and
      incidence of activation in the sternocleidomastoid (startle indicator) from
      participants completing either a simple or choice reaction time (RT) task.
      Consistent with predictions, results indicated that the startle reflex habituated
      after several presentations of the SAS for the choice RT group but not for the
      simple RT group, which we attributed to advance motor preparatory processes
      involved in a simple RT task. Additionally, when participants from the choice RT
      group were put into a simple RT condition, the startle reflex response returned
      to nonhabituated levels. We conclude that the increased corticospinal activation
      associated with advance preparation may also result in increased subcortical
      activation, accounting for the observed lack of habituation to a startling
      stimulus in simple RT.

PMID- 22642892
TI  - A review of training opportunities for ultrasonography in low and middle income
      countries.
AB  - OBJECTIVE: To review the current training opportunities for ultrasound use for
      health workers practising in low- and middle-income countries (LMICs). METHODS: A
      PubMed search using terms ultrasound, sonography, echocardiography, developing
      country/countries, developing world, low resource settings, low income
      country/countries, training and education was conducted. Articles from 2000 to
      2011 that included data on ultrasonography training were eligible for inclusion.
      RESULTS: This review shows that most ultrasound scans are performed by generalist
      and obstetric physicians and even non-medical personnel with little to no formal
      training in ultrasonography. The spectrum of ultrasonography training described
      spanned from no formal training to formal certification and residency programmes.
      All courses included some component of didactics and hands-on training. Follow-up
      of trainee skills ranged from none, to telemedicine case review, to formal re
      evaluations and intensive refresher courses. Ultrasonographic training in LMICs
      often does not meet the WHO criteria such as the number of scans under
      supervision and length of training programme recommended by WHO. Nevertheless,
      some programmes manage to have excellent outcomes with regard to diagnostic
      accuracy and retention of knowledge by trained personnel. CONCLUSION: Regulation
      and quality control of training in ultrasound skills for those working in LMICs
      can be improved. Research on effective training and follow-up should be
      encouraged.

PMID- 22642893
TI  - Heparin-induced skin lesions.
AB  - Heparins are widely used for prophylaxis and treatment of thromboembolic
      diseases. Besides bleeding complications, heparin-induced skin lesions are the
      most frequent unwanted adverse effects of subcutaneous heparin treatment.
      Evidence suggests that these lesions are more common than previously thought.
      Lesions are most frequently due to either allergic reactions or to possibly life
      threatening heparin-induced thrombocytopenia. Early recognition and adequate
      treatment are highly important, because although both complications initially
      show a similar clinical picture, their treatment should be fundamentally
      different. Furthermore, risk factors associated with the patient, drug, and
      treatment regimen have been identified. We review the clinical range of heparin
      induced skin lesions, emphasise evidence and controversies in epidemiology,
      diagnosis, and differential diagnosis, and discuss the management of patients
      with these skin lesions.

PMID- 22642894
TI  - Combinatorial antitumor effect of naringenin and curcumin elicit angioinhibitory
      activities in vivo.
AB  - Curcumin has long been used as an antioxidative, antiinflammatory, and modulator
      of pathological angiogenesis, whereas naringenin is a well-known immunomodulator.
      In this report, we investigated the effect of curcumin and naringenin on the
      growth of Ehrlich ascites carcinoma tumor model. To achieve this, Swiss albino
      mice were implanted intraperitoneally with 1 * 106 Ehrlich ascites carcinoma
      cells followed by the administration of oral doses of naringenin and curcumin
      either individually (50 mg/kg body weight) or in combination (20 mg/kg body
      weight each). A marked reduction has been seen in the total number of cells (80%)
      and accumulation of ascetic fluid (55%) when these drugs were administered
      together. These drugs proved to be an effective angio-inhibitory compound and
      confirmed by different in vivo assay systems, viz. peritoneal/skin angiogenesis
      and chorioallantoic membrane assay. Antiangiogenic and antiproliferative effect
      of these compounds alone or in combination was further corroborated with
      immunoblot results where we confirmed the downregulation of vascular endothelial
      growth factor, Hif1alpha, heat shock protein 90, and p-Akt. Furthermore,
      treatment with naringenin and curcumin alone or in combination substantially
      improved hepatocellular architecture and no noticeable neoplastic lesions or
      cellular alteration were reported. These outcomes put forward a plausible
      clinical application of these diet-derived compounds, as both angioinhibitory and
      antitumor in association with conventional therapy.

PMID- 22642895
TI  - Use of microscopy to assess bran removal patterns in milled rice.
AB  - During rice milling, the bran and germ are successively removed from the
      caryopsis (kernel). Because bran and germ contain large quantities of lipid, the
      amount of lipid remaining on the kernel surface may be used as a method for the
      assessment of milling quality. Bulk samples of rice pureline varieties and an
      experimental hybrid were milled for 0, 10, 20, 30, and 40 s. Scanning electron
      microscopy (SEM) revealed that brown rice kernels had large contours of linear
      protuberances and depressions running lengthwise along the kernel surface. The
      protuberances were abraded successively during milling, but varying amounts of
      material remained in the depressions. Light microscopy combined with the lipid
      specific probes Nile Blue A or Sudan Black B demonstrated that the material in
      the depressions observed with SEM was lipid. Sections of whole, milled rice
      kernels, prepared using a modified sectioning technique and stained with Nile
      Blue A, showed that portions of the embryo remain after milling and that lipid is
      located on or near the surface of the kernel. Differences in quantity and
      distribution of residual lipid as milling duration increased were documented
      photographically to indicate the extent to which the bran and embryo components
      were removed during milling. This paper provides proof of concept that residual
      lipid is a robust measure of the degree of milling.

PMID- 22642896
TI  - Detection of high-frequency and novel DNMT3A mutations in acute myeloid leukemia
      by high-resolution melting curve analysis.
AB  - DNA methyltransferase 3A (DNMT3A) is mutated in a subset of de novo acute myeloid
      leukemia patients and is associated with poor overall and event-free survival.
      Because routine Sanger sequencing of the 23 DNMT3A exons is impractical in
      clinical laboratories, we developed a high-throughput method using high
      resolution melting (HRM) analysis, which identifies sequence variants by
      detecting subtle changes in the melting patterns of mutant DNA in comparison with
      WT sequences. DNA from 104 acute myeloid leukemia patients was tested for
      mutations in 12 exons encoding 3 major functional domains of DNMT3A: the PWWP
      (proline-tryptophan-tryptophan-proline) domain (exons 8 to 10), the ADD (ATM
      DNMT3-DNMT3L) zinc finger, and the methyltransferase domains encoded by exons 15
      to 23. HRM analysis identified 20 of 104 patient samples as variants, which we
      confirmed by Sanger sequencing. Codon 882 of exon 23 was mutated at the highest
      frequency with an occurrence rate of 11.5%. All HRM WT calls were confirmed to be
      devoid of mutations by Sanger sequencing. We also identified seven novel and
      previously unreported DNMT3A mutations. Structural modeling showed seven of the
      eight missense mutations detected in our study increased the free energy,
      destabilized protein, and altered solvent accessibility, suggesting their loss-of
      function nature. These data demonstrate HRM analysis to be a higher throughput,
      sensitive, and efficient alternative to Sanger sequencing for detecting DNMT3A
      mutations in the clinical diagnostic laboratory.

PMID- 22642897
TI  - Development of plasmid calibrators for absolute quantification of miRNAs by using
      real-time qPCR.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs of approximately 18 to 25 nucleotides
      in length that negatively regulate gene expression via either the degradation or
      translational inhibition of their target mRNAs. Because miRNAs are essential for
      the regulation of critical physiological processes as well as a variety of
      pathological events, they have emerged as a novel class of molecular diagnostic
      biomarkers and therapeutic agents or targets. Accordingly, the need for novel
      methods for the quantification of miRNA has increased due to interest in their
      clinical implications. Currently, real-time quantitative polymerase chain
      reaction (qPCR) is considered the most robust technology for nucleic acid
      quantification. Different tools for miRNA quantification by using qPCR are now
      commercially available, but only relative quantification strategies have been
      reported. This situation may be partly due to the difficulty in obtaining an
      appropriate molecule with which to establish an miRNA calibration range. Here, we
      describe a rapid and convenient strategy for the development of a calibrator,
      which enables the absolute quantification of miRNAs by using qPCR and allows the
      cloning of a synthetic sequence of interest instead of a PCR product into a
      plasmid.

PMID- 22642898
TI  - Improved method of detecting the ERG gene rearrangement in prostate cancer using
      combined dual-color chromogenic and silver in situ hybridization.
AB  - The recently detected TMPRSS2-ERG fusion gene was revealed as a recurrent and
      prevalent prostate cancer (PCa)-specific event, potentially qualifying it for
      clinical use. To detect this alteration, fluorescence in situ hybridization
      (FISH) is the method of choice. However, FISH has some disadvantages for
      widespread adoption in clinical practice. Subsequently, chromogenic in situ
      hybridization, which uses organic chromogens, and enzymatic metallography silver
      in situ hybridization have emerged as promising bright-field alternatives.
      Compared with chromogenic in situ hybridization, silver in situ hybridization
      signals are very distinct and superior with regard to signal clarity and
      resolution, but the method excludes multicolor protocols. Based on the ERG break
      apart FISH assay, we established a dual-color ERG break-apart assay using
      combined chromogenic in situ hybridization and silver in situ hybridization (CS
      ISH) and compared these results with those obtained by FISH. We assessed 178 PCa
      and 10 benign specimens for their ERG rearrangement status by applying dual-color
      FISH and CS-ISH ERG break-apart assays to consecutive sections. We observed a
      highly significant concordance (97.7%) between FISH- and CS-ISH-based results
      (Pearson's correlation coefficient = 0.955, P < 0.001). Our findings demonstrate
      that the ERG rearrangement status can reliably be assessed by CS-ISH. Further,
      the CS-ISH technique combines the accuracy and precision of FISH with the ease of
      bright-field microscopy. This tool allows a much broader spectrum of applications
      in which to study the biological role and clinical use of ERG rearrangements in
      PCa.

PMID- 22642899
TI  - Prevalence of chronic musculoskeletal disorders in elderly Brazilians: a
      systematic review of the literature.
AB  - BACKGROUND: Population ageing is a worldwide phenomenon that has recently
      challenged public healthcare systems. The knowledge of the burden of chronic
      musculoskeletal disorders in elders is still limited, particularly in the
      developing world. This systematic review aimed to investigate the prevalence of
      chronic musculoskeletal disorders in elderly Brazilians. METHODS: A comprehensive
      literature search was performed in five electronic databases (from inception to
      January 2012) and completed by additional searches in reference lists. Two review
      authors independently selected the eligible studies and extracted data on
      participants' characteristics and rates of chronic musculoskeletal disorders. One
      review author extracted methodological quality data. We performed a critical
      synthesis of the results, which were grouped into the diagnoses "chronic
      musculoskeletal pain" or "specific musculoskeletal diagnoses". RESULTS: Twenty
      five studies reporting on a total of 116,091 elderly Brazilians were included.
      Eight studies (32%) were of high methodological quality. There was a large
      variation in the measure of prevalence used by individual studies and in their
      definition of chronic pain. Prevalence estimates reached 86% for chronic
      musculoskeletal pain in any location. Studies investigating multiple pain sites
      found the lower limb and the spine to be the most prevalent complaints (50%
      each). Arthritis and rheumatism (including osteoarthritis) were the most
      prevalent specific musculoskeletal diagnoses (9% to 40%), followed by herniated
      disc (6% to 27%). CONCLUSIONS: Despite the growth of the elderly population
      worldwide, high-quality research on the burden of chronic musculoskeletal
      disorders in the elderly is still scarce. Future healthcare research focusing on
      this age group should be a priority in developing countries since their public
      healthcare systems are not yet fully prepared to accommodate the needs of an
      aging population.

PMID- 22642900
TI  - Regulation of RAP1B by miR-139 suppresses human colorectal carcinoma cell
      proliferation.
AB  - BACKGROUND: MicroRNAs (miRNAs) are strongly implicated in carcinogenesis, but
      their specific roles in the major cancers have yet to be fully elucidated.
      METHODS: The expression levels of miR-139 in colorectal carcinoma and paired
      normal tissues were examined using real-time PCR assays. Potential functions of
      miR-139 were evaluated in colorectal carcinoma cell lines (SW480, SW620, LS174 T,
      and HCT116) using miR-139 mimics, anti-miR-139, and siRNA RAP1B. RESULTS: In this
      study, we determined that miR-139 is down-regulated in colorectal carcinoma (CRC)
      tissues. Lower miR-139 expression correlates with more advanced CRC and lower
      overall survival of patients with CRC. The ectopic expression of miR-139 in human
      CRC cells decreased cell growth and tumorigenicity, whereas the silencing of miR
      139 promoted cell growth. Mechanistic studies revealed that miR-139 repressed the
      activity of a reporter gene fused to the 3'-untranslated region of RAP1B, whereas
      miR-139 silencing up-regulated the expression of the reporter gene. RNAi-mediated
      knockdown of RAP1B phenocopied the antiproliferative effect of miR-139, whereas
      the overexpression of RAP1B blocked miR-139-mediated antiproliferative effects in
      CRC cells. CONCLUSIONS: Taken together, these results demonstrated that miR-139
      decreases proliferation by directly targeting RAP1B, defining miR-139 as a new
      putative tumour suppressor miRNA in CRC.

PMID- 22642901
TI  - Chronic atrophic erosive dermatosis of the scalp and atypical fibroxanthoma: a
      rare association.

PMID- 22642903
TI  - Blepharoptosis following anterior segment surgery: a new theory for an old
      problem.
AB  - Blepharoptosis is a well-known complication following anterior segment surgery.
      However, its precise aetiology remains elusive. There are currently two widely
      held views on the pathogenesis of persistent postoperative ptosis, namely the
      speculum and bridle suture theories. However, both suggested explanations fail to
      address important anatomical and epidemiological features of this condition.
      Until now, the majority of published literature describing persistent
      postoperative ptosis following anterior segment surgery has largely concentrated
      on dehiscence of the levator aponeurosis as the common mechanism underlying this
      postoperative complication. However, numerous studies have failed to show any
      correlation between pre or postoperative skin crease positions in such patients.
      This review article discusses previously proposed mechanisms responsible for both
      transient and persistent ptosis. Furthermore, we propose an alternative mechanism
      for the development of ptosis following anterior segment surgery, namely
      horizontal stretch of the upper eyelid induced by the use of the speculum. This
      mechanism also provides a plausible explanation for less commonly described
      oculoplastic complications, such as lower lid malpositions, following anterior
      segment surgery. Postoperative ptosis may also act as a paradigm for the
      development of involutional ptosis in general. In view of the frequency with
      which ophthalmologists perform anterior segment procedures such as cataract
      surgery, postoperative ptosis represents a significant concern for all ocular
      surgeons. Identifying the underlying mechanism is imperative, not only to
      identify those patients at greatest risk, but also to perhaps provide novel
      surgical approaches to the management of this complication.

PMID- 22642902
TI  - Gelation characteristics and osteogenic differentiation of stromal cells in inert
      hydrolytically degradable micellar polyethylene glycol hydrogels.
AB  - The use of poly(ethylene glycol) (PEG) hydrogels in tissue engineering is limited
      by their persistence in the site of regeneration. In an attempt to produce inert
      hydrolytically degradable PEG-based hydrogels, star (SPELA) poly(ethylene glycol
      co-lactide) acrylate macromonomers with short lactide segments (<15 lactides per
      macromonomer) were synthesized. The SPELA hydrogel was characterized with respect
      to gelation time, modulus, water content, sol fraction, degradation, and
      osteogenic differentiation of encapsulated marrow stromal cells (MSCs). The
      properties of SPELA hydrogel were compared with those of the linear poly(ethylene
      glycol-co-lactide) acrylate (LPELA). The SPELA hydrogel had higher modulus, lower
      water content, and lower sol fraction than the LPELA. The shear modulus of SPELA
      hydrogel was 2.2 times higher than LPELA, whereas the sol fraction of SPELA
      hydrogel was 5 times lower than LPELA. The degradation of SPELA hydrogel depended
      strongly on the number of lactide monomers per macromonomer (nL) and showed a
      biphasic behavior. For example, as nL increased from 0 to 3.4, 6.4, 11.6, and
      14.8, mass loss increased from 7 to 37, 80, 100% and then deceased to 87%,
      respectively, after 6 weeks of incubation. The addition of 3.4 lactides per
      macromonomer (<10 wt % dry macromonomer or <2 wt % swollen hydrogel) increased
      mass loss to 50% after 6 weeks. Molecular dynamic simulations demonstrated that
      the biphasic degradation behavior was related to aggregation and micelle
      formation of lactide monomers in the macromonomer in aqueous solution. MSCs
      encapsulated in SPELA hydrogel expressed osteogenic markers Dlx5, Runx2,
      osteopontin, and osteocalcin and formed a mineralized matrix. The expression of
      osteogenic markers and extent of mineralization was significantly higher when
      MSCs were encapsulated in SPELA hydrogel with the addition of bone morphogenetic
      protein-2 (BMP2). Results demonstrate that hydrolytically degradable PEG-based
      hydrogels are potentially useful as a delivery matrix for stem cells in
      regenerative medicine.

PMID- 22642904
TI  - XRCC1 Arg399Gln was associated with repair capacity for DNA damage induced by
      occupational chromium exposure.
AB  - BACKGROUND: Occupational chromium exposure may induce DNA damage and lead to lung
      cancer and other work-related diseases. DNA repair gene polymorphisms, which may
      alter the efficiency of DNA repair, thus may contribute to genetic susceptibility
      of DNA damage. The aim of this study was to test the hypothesis that the genetic
      variations of 9 major DNA repair genes could modulate the hexavalent chromium (Cr
      (VI))-induced DNA damage. FINDINGS: The median (P25-P75) of Olive tail moment was
      0.93 (0.58-1.79) for individuals carrying GG genotype of XRCC1 Arg399Gln (G/A),
      0.73 (0.46-1.35) for GA heterozygote and 0.50 (0.43-0.93) for AA genotype.
      Significant difference was found among the subjects with three different
      genotypes (P = 0.048) after adjusting the confounding factors. The median of
      Olive tail moment of the subjects carrying A allele (the genotypes of AA and GA)
      was 0.66 (0.44-1.31), which was significantly lower than that of subjects with GG
      genotype (P = 0.043). The A allele conferred a significantly reduced risk of DNA
      damage with the OR of 0.39 (95% CI: 0.15-0.99, P = 0.048). No significant
      association was found between the XRCC1Arg194Trp, ERCC1 C8092A, ERCC5 His1104Asp,
      ERCC6 Gly399Asp, GSTP1 Ile105Val, OGG1 Ser326Cys, XPC Lys939Gln, XPD Lys751Gln
      and DNA damage. CONCLUSION: The polymorphism of Arg399Gln in XRCC1 was associated
      with the Cr (VI)- induced DNA damage. XRCC1 Arg399Gln may serve as a genetic
      biomarker of susceptibility for Cr (VI)- induced DNA damage.

PMID- 22642905
TI  - Endostitch and endostapler assisted transoral endoscopic Zenker's
      diverticulostomy.

PMID- 22642906
TI  - A historical perspective on sepsis.
AB  - In North America, approximately 700,000 cases of sepsis occur each year, with
      mortality ranging between 30% and 50%. The American Journal of Pathology has
      featured numerous articles on the topic, revealing mechanistic insights gleaned
      from both experimental rodent models and human sepsis. Nonetheless, there remains
      urgent need to determine the basis for sepsis-related complications and how they
      can be avoided, as well as how they can be most effectively treated once
      recognized. This historical perspective reviews what we currently understand
      about the mechanisms of sepsis, as well as the barriers that remain in our
      treatment strategies.

PMID- 22642907
TI  - Enhancement of antibody-induced arthritis via Toll-like receptor 2 stimulation is
      regulated by granulocyte reactive oxygen species.
AB  - The suppressive role of phagocyte nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase (NOX2) complex-derived reactive oxygen species (ROS) in adaptive
      immunity-driven arthritis models is well established. In this study, we aimed to
      investigate the role of NOX2 complex-derived ROS in a model of innate immunity
      driven arthritis and to identify the ROS-regulated innate receptors that control
      arthritis. We used collagen antibody-induced arthritis (CAIA), which is a T and B
      lymphocyte-independent model of the effector phase of arthritis and is induced by
      well-defined monoclonal arthritogenic antibodies and enhanced by injection of
      lipopolysaccharide (LPS). CAIA was induced in both wild-type and Ncf1 mutant mice
      that lack phagocyte oxidative burst, and stimulated with LPS and other agents to
      activate innate immune responses. We found that both LPS and lipomannan enhanced
      CAIA more potently in the presence of functional phagocyte ROS production than in
      its absence. The ROS-dependent enhancement of CAIA was regulated by TLR2, but not
      by TLR4 stimulation, and was driven by granulocytes, whereas macrophages did not
      contribute to the phenotype. In addition, we report that collagen-induced
      arthritis was not affected by the functionality of the TLR4. We report that TLR2
      signaling as an important ROS-regulated proinflammatory pathway leads to severe
      neutrophil-dependent inflammation in murine CAIA and conclude that the TLR2
      pathway is modulated by phagocyte ROS to stimulate the development of arthritis.

PMID- 22642908
TI  - Methotrexate chemotherapy promotes osteoclast formation in the long bone of rats
      via increased pro-inflammatory cytokines and enhanced NF-kappaB activation.
AB  - Cancer chemotherapy with methotrexate (MTX) is known to cause bone loss. However,
      the underlying mechanisms remain unclear. This study investigated the potential
      role of MTX-induced pro-inflammatory cytokines and activation of NF-kappaB in the
      associated osteoclastogenesis in rats. MTX (0.75 mg/kg per day) was administered
      for 5 days, and bone and bone marrow specimens were collected on days 6, 9, and
      14. Compared with a normal control, MTX increased the density of osteoclasts
      within the metaphyseal bone and the osteoclast formation potential of marrow
      cells on day 9. RT-PCR analysis of mRNA expression for pro-osteoclastogenic
      cytokines in the metaphysis indicated that, although the receptor activator of NF
      kappaB ligand/osteoprotegerin axis was unaffected, expression of tumor necrosis
      factor (TNF)-alpha, IL-1, and IL-6 increased on day 9. Enzyme-linked
      immunosorbent assay analysis of plasma showed increased levels of TNF-alpha on
      day 6 and of IL-6 on day 14. Plasma from treated rats induced osteoclast
      formation from normal bone marrow cells, which was attenuated by a TNF-alpha
      neutralizing antibody. Indicative of a role for NF-kappaB signaling, plasma on
      day 6 increased NF-kappaB activation in RAW(264.7) cells, and plasma-induced
      osteoclastogenesis was abolished in the presence of the NF-kappaB inhibitor,
      parthenolide. Our results demonstrate mechanisms for MTX-induced
      osteoclastogenesis and show that MTX induces osteoclast differentiation by
      generating a pro-osteoclastogenic environment in both bone and the circulation,
      specifically with increased TNF-alpha levels and activation of NF-kappaB.

PMID- 22642909
TI  - Virus-like particle-induced protection against MRSA pneumonia is dependent on IL
      13 and enhancement of phagocyte function.
AB  - The importance of the priming of the lung environment by past infections is being
      increasingly recognized. Exposure to any given antigen can either improve or
      worsen the outcome of subsequent lung infections, depending on the immunological
      history of the host. Thus, an ability to impart transient alterations in the lung
      environment in anticipation of future insult could provide an important novel
      therapy for emerging infectious diseases. In this study, we show that nasal
      administration of virus-like particles (VLPs) before, or immediately after,
      lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA) of mice
      i) ensures complete recovery from lung infection and near absolute clearance of
      bacteria within 12 hours of challenge, ii) reduces host response-induced lung
      tissue damage, iii) promotes recruitment and efficient bacterial clearance by
      neutrophils and CD11c(+) cells, and iv) protects macrophages from MRSA-induced
      necrosis. VLP-mediated protection against MRSA relied on innate immunity.
      Complete recovery occurred in VLP-dosed mice with severe combined
      immunodeficiency, but not in wild-type mice depleted of either Ly6G(+) or
      CD11c(+) cells. Early IL-13 production associated with VLP-induced CD11c(+) cells
      was essential for VLP-induced protection. These results indicate that VLP-induced
      alteration of the lung environment protects the host from lethal MRSA pneumonia
      by enhancing phagocyte recruitment and killing and by reducing inflammation
      induced tissue damage via IL-13-dependent mechanisms.

PMID- 22642910
TI  - Low alpha(2)beta(1) integrin function enhances the proliferation of fibroblasts
      from patients with idiopathic pulmonary fibrosis by activation of the beta
      catenin pathway.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and incurable
      fibroproliferative disorder characterized by unrelenting proliferation of
      fibroblasts and their deposition of collagen within alveoli, resulting in
      permanently scarred, nonfunctional airspaces. Normally, polymerized collagen
      suppresses fibroblast proliferation and serves as a physiological restraint to
      limit fibroproliferation after tissue injury. The IPF fibroblast, however, is a
      pathologically altered cell that has acquired the capacity to elude the
      proliferation-suppressive effects of polymerized collagen. The mechanism for this
      phenomenon remains incompletely understood. Here, we demonstrate that expression
      of alpha(2)beta(1) integrin, a major collagen receptor, is pathologically low in
      IPF fibroblasts interacting with polymerized collagen. Low integrin expression in
      IPF fibroblasts is associated with a failure to induce PP2A phosphatase activity,
      resulting in abnormally high levels of phosphorylated (inactive) GSK-3beta and
      high levels of active beta-catenin in the nucleus. Knockdown of beta-catenin in
      IPF fibroblasts inhibits their ability to proliferate on collagen. Interdiction
      of alpha(2)beta(1) integrin in control fibroblasts reproduces the IPF phenotype
      and leads to the inability of these cells to activate PP2A, resulting in high
      levels of phosphorylated GSK-3beta and active beta-catenin and in enhanced
      proliferation on collagen. Our findings indicate that the IPF fibroblast
      phenotype is characterized by low alpha(2)beta(1) integrin expression, resulting
      in a failure of integrin to activate PP2A phosphatase, which permits
      inappropriate activation of the beta-catenin pathway.

PMID- 22642912
TI  - Estrogen modulates osteogenic activity and estrogen receptor mRNA in mesenchymal
      stem cells of women.
AB  - OBJECTIVE: To determine whether estrogen regulates mesenchymal stem cell (MSC)
      activity in bone marrow from osteoporotic postmenopausal women. METHODS: MSCs
      were collected from bone marrows which were aspirated simultaneously during iliac
      bone graft procedures in spine fusion surgery in osteoporotic postmenopausal
      women. We investigated proliferation, differentiation, osteogenic activity, and
      estrogen receptor (ER) alpha and beta mRNA expression of primary culture MSCs
      isolated from four osteoporotic postmenopausal women, treated in vitro with or
      without 17beta-estradiol. The expression of alkaline phosphatase (ALP),
      osteocalcin, interleukin-6, ERalpha and ERbeta mRNA was evaluated. RESULTS: The
      expression of ALP and osteocalcin mRNA was detected during the cultures of MSCs
      and was observed to increase up to day 20. As compared with MSCs not treated with
      estradiol, a significant increase in DNA content, ERalpha mRNA, and ALP mRNA
      expression was observed in cultures with estradiol. The mRNA expression of
      osteocalcin and interleukin-6 was significantly lower in MSCs treated with
      estradiol than those without estradiol. There was no significant difference in
      the mRNA expression of ERbeta between MSCs cultured with and without estradiol.
      CONCLUSIONS: In the proper environment, MSCs from osteoporotic women can
      differentiate into osteoblasts and estrogen enhances the osteogenic activity
      possibly via ERalpha activity.

PMID- 22642911
TI  - Retrograde and Wallerian axonal degeneration occur synchronously after retinal
      ganglion cell axotomy.
AB  - Axonal injury and degeneration are pivotal pathological events in diseases of the
      nervous system. In the past decade, it has been recognized that the process of
      axonal degeneration is distinct from somal degeneration and that axoprotective
      strategies may be distinct from those that protect the soma. Preserving the cell
      body via neuroprotection cannot improve function if the axon is damaged, because
      the soma is still disconnected from its target. Therefore, understanding the
      mechanisms of axonal degeneration is critical for developing new therapeutic
      interventions for axonal disease treatment. We combined in vivo imaging with a
      multilaser confocal scanning laser ophthalmoscope and in vivo axotomy with a
      diode-pumped solid-state laser to assess the time course of Wallerian and
      retrograde degeneration of unmyelinated retinal ganglion cell axons in living
      rats for 4 weeks after intraretinal axotomy. Laser injury resulted in
      reproducible axon loss both distal and proximal to the site of injury.
      Longitudinal polarization-sensitive imaging of axons demonstrated that Wallerian
      and retrograde degeneration occurred synchronously. Neurofilament immunostaining
      of retinal whole-mounts confirmed axonal loss and demonstrated sparing of
      adjacent axons to the axotomy site. In vivo fluorescent imaging of axonal
      transport and photobleaching of labeled axons demonstrated that the laser axotomy
      model did not affect adjacent axon function. These results are consistent with a
      shared mechanism for Wallerian and retrograde degeneration.

PMID- 22642913
TI  - Exacerbated metastatic disease in a mouse mammary tumor model following latent
      gammaherpesvirus infection.
AB  - BACKGROUND: Controversy exists as to the ability of human gammaherpesviruses to
      cause or exacerbate breast cancer disease in patients. The difficulty in
      conducting definitive human studies can be overcome by investigating developing
      breast cancer in a mouse model. In this study, we utilized mice latently infected
      with murine gammaherpesvirus 68 (HV-68) to question whether such a viral burden
      could exacerbate metastatic breast cancer disease using a mouse mammary tumor
      model. RESULTS: Mice latently infected with HV-68 had a similar primary tumor
      burden, but much greater metastatic disease, when compared to mock treated mice
      given the transplantable tumor, 4 T1. This was true for lung lesions, as well as
      secondary tumor masses. Increased expression of pan-cytokeratin and VEGF-A in
      tumors from HV-68 infected mice was consistent with increased metastatic disease
      in these animals. Surprisingly, no viral particles could be cultured from tumor
      tissues, and the presence of viral DNA or RNA transcripts could not be detected
      in primary or secondary tumor tissues. CONCLUSIONS: Latent HV-68 infection had no
      significant effect on the size of primary 4 T1 mammary tumors, but exacerbated
      the number of metastatic lung lesions and secondary tumors when compared to mock
      treated mice. Increased expression of the tumor marker, pan-cytokeratin, and VEGF
      A in tumors of mice harboring latent virus was consistent with an exacerbated
      metastatic disease. Mechanisms responsible for this exacerbation are indirect,
      since no virus could be detected in cancerous tissues.

PMID- 22642914
TI  - Pathogenesis of group A streptococcal infections.
AB  - Group A Streptococcus (GAS; Streptococcus pyogenes) is a human pathogen which
      causes significant morbidity and mortality globally. GAS typically infects the
      throat and skin of the host, causing mild infections such as pharyngitis and
      impetigo, in addition to life threatening conditions including necrotizing
      fasciitis, streptococcal toxic shock syndrome (STSS), and bacteremia. Repeated
      infection with GAS may result in the non-suppurative sequelae, acute rheumatic
      fever, and acute glomerulonephritis. GAS remains sensitive to the antibiotic
      penicillin which can be administered as a means to treat infection or as
      prophylaxis. However, issues with patient compliance and a growing concern over
      the possible emergence of resistant GAS strains may limit the usefulness of
      antibiotics in the future. A vaccine capable of preventing GAS infection may be
      the only effective way to control and eliminate GAS infection and disease.

PMID- 22642915
TI  - New advances in the mechanisms and etiology of carpal tunnel syndrome.
AB  - In recent years, knowledge about the etiological mechanisms of carpal tunnel
      syndrome (CTS) has evolved significantly, allowing for a better understanding of
      this pain syndrome. Some studies have demonstrated that patients with CTS exhibit
      sensory symptoms not only within the areas innervated by the median nerve but
      also in extra-median regions, i.e., forearm or shoulder. It has also been
      demonstrated that patients with CTS may exhibit widespread pressure
      hypersensitivity and generalized thermal hyperalgesia, but not hypoesthesia,
      which is not related to electro-diagnostic findings. In addition, fine motor
      control and pinch grip force disturbances have been found to be commonly observed
      in this patient population. All these data suggest that central sensitization
      mechanisms are involved in the somato-sensory and motor disturbances found in
      CTS, probably related to cortical plastic changes. The presence of sensitization
      mechanisms could play an important role in the development of bilateral sensory
      symptoms in CTS and also can determine the therapeutic strategies for this
      condition. We propose that therapeutic interventions applied to individuals with
      CTS should include approaches that would modulate nociceptive barrage into the
      central nervous system.

PMID- 22642916
TI  - Does periodontopathic bacterial infection contribute to the etiopathogenesis of
      the autoimmune disease rheumatoid arthritis?
AB  - There is a significant association between rheumatoid arthritis (RA) and
      periodontal disease (PD). Patients with longstanding active RA have been found to
      have a substantially increased frequency of PD compared with healthy subjects.
      Further, patients with PD have been shown to have a higher prevalence of RA than
      patients without periodontitis. Antibodies to Gram-negative, anaerobic
      periodontal pathogens such as Porphyromonas gingivalis, Prevotella intermedia,
      Prevotella melaninogenica, and Tannerella forsythia have been detected in the
      serum and synovial fluid of RA patients. These pathogens have also been
      identified in the synovial fluid of RA patients, with higher levels of bacterial
      DNA in RA patients than in controls. This review examines the association between
      periodontopathic bacteria and the etiology of RA.

PMID- 22642917
TI  - Gastrointestinal stromal tumors (GIST): a rare entity, a tumor model for
      personalized therapy, and yet ten different molecular subtypes.
AB  - Gastrointestinal stromal tumors (GIST) are the most frequent sarcoma and were
      recognized as distinct molecular entities in 1998. Following the identification
      of driving molecular alterations in KIT, imatinib was rapidly introduced for the
      treatment of GIST, and became the paradigm of molecularly targeted therapies for
      solid tumors. While surgery was the only known effective treatment in 1998, two
      drugs are approved by the FDA and EMA in 2012 for the treatment of localized and
      advanced forms of this disease. Imatinib has been shown to provide a high level
      of clinical efficacy in patients with advanced GIST, a median progression-free
      survival (PFS) of 2 years and median overall survival close to 5 years, with 20%
      patients progression-free after 10 years of treatment. Imatinib has also been
      proven to improve overall survival and reduce the risk of relapse in localized
      GIST at high risk for relapse after resection. Sunitinib is indicated in advanced
      GIST after failure of imatinib, and provided a median PFS close to 6 months after
      imatinib failure. However, there is an important variability in the molecular and
      genetic characteristics that drive the pathogenesis of GIST, allowing thus for
      the identification of distinct molecular subtypes of GIST with different
      prognosis and sensitivity to the targeted treatments. Different strategies are
      now recommended in these different molecular subtypes of GIST which must be
      recognized as different entities regarding sensitivity to tyrosine kinase
      inhibitors and treatment decisions. This fragmentation of a yet recently
      recognized disease entity illustrates to strong trend of fragmentation in
      nosology of cancers, even in rare tumors such as GIST. For this aspect also, GIST
      is again a paradigmatic model for oncology, as many tumors with a higher
      prevalence will be fragmented in different molecular subsets and are going to
      become rare disease in the years to come.

PMID- 22642918
TI  - Therapeutic effects of plasma exchange for the treatment of 39 patients with
      acute fatty liver of pregnancy.
AB  - AIM: Analysis of the efficacy and timing of plasma exchange (PE) in the treatment
      of acute fatty liver of pregnancy (AFLP). METHODS: The clinical data of 39 cases
      of AFLP treated with PE from September 2004 to March 2011 include symptoms,
      physical signs, adverse effects, and all relevant laboratory test results before
      and after PE. RESULTS: (1) Adverse reactions during PE were generally mild and
      tolerable, and no patients discontinued treatment due to adverse events;
      symptoms, physical signs, and liver and kidney functions improved significantly
      after PE (P<0.05); (2) of the 39 cases treated, 37 were cured, 2 died, with a
      cure rate of 94.87%; (3) of the 37 cases cured, the sooner a patient received PE
      the faster the recovery and the fewer number of PEs needed for a complete
      recovery (P<0.01). CONCLUSION: Treatment of AFLP by PE is safe and effective, and
      timely application of PE in the early phase of the disease can effectively halt
      and reverse the progression of AFLP.

PMID- 22642919
TI  - Advances in management of acute hypertension: a concise review.
AB  - Chronic hypertension affects >1 billion people worldwide and >70 million people
      in the United States. Acute hypertensive episodes (AHE) are defined as severe
      spikes in blood pressure that may result in end-organ damage. Although AHE may
      arise independently as de novo events, they are more likely to occur in patients
      with pre-existing hypertension. One of the controversies regarding the clinical
      approach to AHE is the selection of anti-hypertensive medication. Depending on
      the clinical presentation of the patient and the threat of end-organ damage
      resulting from blood pressure elevation, appropriate and prompt treatment is
      warranted. There are multiple agents available for the management of
      hypertension. However, the greatest challenge lies in the acute care setting
      where the need exists for better initial and sustained control of blood pressure
      spikes. Many anti-hypertensive agents effectively lower blood pressure, yet only
      few have the capacity to achieve strict control of hypertension in the acute
      setting. Clevidipine butyrate is an ultra short-acting intravenous
      dihydropyridine calcium-channel blocker. Clevidipine has unique pharmacodynamic
      and pharmacokinetic properties that enable the fast, safe, and adequate reduction
      of blood pressure in hypertensive emergencies, with the ability to provide highly
      precise titration necessary to maintain a narrowly-defined target blood pressure
      range. Several recently published phase I, II, and III clinical studies have
      shown Clevidipine to be an effective blood pressure modulator in such capacity.

PMID- 22642920
TI  - Current state and future challenges of chemoprevention.
AB  - There have been numerous chemoprevention trials in the past 10 years, but the
      number of approved chemoprevention drugs is still quite small. This is likely due
      to a number of factors, but two consistent problems in the field of
      chemoprevention have been the lack of efficacy with or without unacceptable
      toxicity, and unexpected toxicity or fear of it associated with most of the
      approaches. This review intends to describe the types of chemoprevention as well
      as highlight recent successes and failures. We will also discuss potential
      solutions for the problems of limited efficacy and toxicity.

PMID- 22642921
TI  - Divalent base cations hamper Hg(II) uptake.
AB  - Despite the alarming trends of declining base cation concentrations in boreal
      lakes, no studies have attempted to predict the consequences of this decline on
      the geochemical cycle of mercury, a top priority contaminant worldwide. In this
      study, we used a whole-cell gram-negative bioreporter to evaluate the direction
      and magnitude of changes in net accumulation of Hg(II) by bacteria in response to
      changing base cation concentrations. We show that regardless of the speciation of
      Hg(II) in solution, increasing divalent base cation concentrations decrease net
      Hg(II) accumulation by the bioreporter, suggesting a protective effect of these
      cations. Our work suggests that the complexity of the cell wall of gram-negative
      bacteria must be considered when modeling Hg uptake pathways; we propose that
      base divalent cations contribute to hamper net Hg(II) accumulation by decreasing
      outer membrane permeability and, therefore, the passive diffusion of Hg(II)
      species to the periplasmic space. This work points to an unsuspected and likely
      harmful consequence of a delay in recovering from acidification in boreal lakes,
      in that uptake of Hg(II) by bacteria is not only enhanced by the reduced pH but
      can also be enhanced by a decline in base cation levels.

PMID- 22642922
TI  - The value of serial plasma nuclear and mitochondrial DNA levels in acute
      spontaneous intra-cerebral haemorrhage.
AB  - BACKGROUND: Increased plasma nuclear and mitochondrial DNA levels may be
      connected to disease severity following spontaneous intra-cerebral haemorrhage
      (ICH). This study tested the hypothesis that plasma nuclear and mitochondrial DNA
      levels are substantially increased in acute ICH and can predict treatment
      outcomes. METHODS: Serial plasma nuclear and mitochondrial DNA levels were
      examined in 60 consecutive patients admitted within 24 h after onset of
      spontaneous ICH and in 60 volunteer control subjects. Additional samples were
      obtained on days 4, 7, 10, and 14 after onset of ICH regardless of clinical
      deterioration. RESULTS: Only plasma nuclear DNA, not plasma mitochondrial DNA,
      levels in patients with spontaneous ICH significantly correlated with Glasgow
      Coma Scale (GCS) (r = -0.467, P = 0.001) and ICH volume (r = 0.515, P <= 0.001)
      on presentation. Plasma nuclear DNA levels increased significantly from day 1 to
      day 7 in patients with poor outcome. Higher plasma nuclear DNA levels (cut-off
      value >18.7 ng/ml) on presentation were associated with poor outcomes in
      spontaneous ICH patients. CONCLUSION: Plasma nuclear DNA levels reflect the
      severity of cerebral damage such that higher levels are associated with poorer
      outcome. Plasma nuclear DNA level can be considered a neuropathologic marker of
      acute spontaneous ICH.

PMID- 22642923
TI  - Accuracy and reproducibility of a retrospective outcome assessment for lumbar
      spinal stenosis surgery.
AB  - BACKGROUND: Retrospective assessment of surgery outcome is considered
      problematic. The aims of this study were to evaluate the reproducibility and
      accuracy of a retrospective outcome assessment of lumbar spinal stenosis surgery
      with reference to prospective outcome scale measurements. METHOD: Outcome of
      surgery from 100 lumbar spinal stenosis (LSS) patients was evaluated
      retrospectively from patient files of a 3-month outpatient visit performed
      according to a standard clinical protocol by two independent researchers. In the
      retrospective analysis, outcome was graded as 2 = good if the clinical condition
      had clearly improved, 1 = moderate if it had just slightly improved, 0 = poor if
      it had not improved or was even worse than before the surgical treatment
      (Retrospective 3- point scale). A prospectively assessed Oswestry Disability
      Index questionnaire (ODI), Visual analogue pain scale (VAS) and a patient
      satisfaction questionnaire were used as references of standards. Reproducibility
      of the measurements was evaluated. RESULTS: The retrospective 3-point scale
      correlated with ODI (r = 0.528; P < 0.001) and VAS (r = 0.368; P < 0.001). The
      agreement was better in the good and poor outcome than in the moderate outcome.
      Retrospective 3-point scale demonstrated substantial intra-rater and inter-rater
      repeatability (kappa = 0.682, P < 0.001 and kappa = 0.630, P < 0.001,
      respectively). CONCLUSIONS: Retrospective assessment of spinal surgery outcome is
      highly reproducible. Accuracy is highest in the patients with poor and good
      surgical result.

PMID- 22642924
TI  - Preparation and evaluation of NGF-microsphere conduits for regeneration of
      defective nerves.
AB  - OBJECTIVES: To fabricate nerve growth factor (NGF) microsphere conduits and
      evaluate their promotional effects on regeneration of defective nerves. METHODS:
      NGF microspheres containing ovalbumin were prepared using a double-emulsion
      method. The total amount of NGF was determined by enzyme-linked immunosorbent
      assay, and bioactive NGF was quantified by the PC12 cell line method; the NGF
      bioactivity present during the release period was monitored. Conduits made of
      polylacticacid were added to the NGF microspheres to bridge and repair the nerve
      injury. The sciatic nerve of Wistar rats was used to evaluate nerve-regeneration
      efficacy. RESULTS: NGF microspheres were spherical, with smooth and compact
      surfaces. The fabrication yield, encapsulation efficiency, and drug loading of
      the microspheres were 58.3, 29.72, and 0.003%, respectively. The monitoring of
      NGF bioactivity remaining during the release period showed that ~40% of the
      original bioactivity was kept on the twenty-eighth day and 10% left on the
      ninetieth day. Polylacticacid conduits are lowly antigenic, porous (facilitates
      oxygen diffusion), and able to prevent long-term compression. After 15 days, the
      length of nerve regenerated from NGF-microsphere conduits was statistically
      different from that of the control groups (P<0.05). NGF microspheres can
      accelerate the early nerve-regeneration rate, although the rate was not as good
      as that caused by autografts. Three months later, the recovery rate of the
      regenerated nerve collected from NGF-microsphere conduits showed lower values of
      nerve-conduction velocity, muscular tension, and muscle weight. However, poorer
      rates of regeneration were observed in the self-mutilation foot compared with
      those of the control group. The control group had no statistical difference from
      the sodium chloride and NGF-solution conduits, the best in the autograft group.
      DISCUSSION: A long-term promoting effect of microsphere-bound exogenous NGF on
      the functional repair of peripheral nerves could not be confirmed, although the
      nerve-regeneration rate was rapid in the early stage. Better methods are needed
      to incorporate protein-release systems into nerve conduits to improve functional
      recovery in patients with injured nerves.

PMID- 22642925
TI  - A time of change at Thrombosis Journal.
AB  - Thrombosis and hemostasis related disease have a heavy burden in cardiovascular
      disease and it is important to have a journal where research into this can be
      accessed by all.

PMID- 22642926
TI  - Induction of male production in clones of Daphnia pulex by the juvenoid hormone
      methyl farnesoate under short photoperiod.
AB  - The juvenile hormone, methyl farnesoate (MF), and its analog insecticides have
      been used successfully to induce the production of males in cladocerans under
      long-day conditions in the laboratory. However, without hormone addition Daphnia
      do not usually produce male offspring under long photoperiods, while short
      photoperiods are a stimulus for the induction of males. We used 21 clones of
      Daphnia pulex differing in their propensity to produce males under short-day
      conditions to test whether the treatment with MF would result in an additive
      effect of shifting the sex ratio towards males. Contrary to our expectations,
      clones with a high tendency of male production showed a reduced sex ratio in
      response to MF treatment under short-day conditions, but clones that produced
      normally few males or did not produce males were stimulated by 700 nM MF to
      produce up to 40% males. We suggest that the endocrine disruptive effect of MF or
      juvenile hormone analogs in the field may depend on the clonal composition of the
      cladoceran population and on the natural photoperiod. This may affect the
      seasonal occurrence of sexual reproduction and eventually cause a mismatch
      between the presence of males and ephippial females.

PMID- 22642927
TI  - Characterization of structure and function of the mouse retina using pattern
      electroretinography, pupil light reflex, and optical coherence tomography.
AB  - OBJECTIVE: To perform in vivo analysis of retinal functional and structural
      parameters in healthy mouse eyes. ANIMAL STUDIED: Adult C57BL/6 male mice (n =
      37). PROCEDURES: Retinal function was evaluated using pattern electroretinography
      (pERG) and the chromatic pupil light reflex (cPLR). Structural properties of the
      retina and nerve fiber layer (NFL) were evaluated using spectral-domain optical
      coherence tomography (SD-OCT). RESULTS: The average pERG amplitudes were found to
      be 11.2 +/- 0.7 MUV (P50-N95, mean +/- SEM), with an implicit time for P50-N95
      interval of 90.4 +/- 5.4 ms. Total retinal thickness was 229.5 +/- 1.7 MUm (mean
      +/- SEM) in the area centralis region. The thickness of the retinal nerve fiber
      layer (mean +/- SEM) using a circular peripapillary retinal scan centered on the
      optic nerve was 46.7 +/- 0.9 MUm (temporal), 46.1 +/- 0.9 MUm (superior), 45.8 +/
      0.9 MUm (nasal), and 48.4 +/- 1 MUm (inferior). The baseline pupil diameter was
      2.1 +/- 0.05 mm in darkness, and 1.1 +/- 0.05 and 0.56 +/- 0.03 mm after
      stimulation with red (630 nm, luminance 200 kcd/m(2)) or blue (480 nm, luminance
      200 kcd/m(2)) light illumination, respectively. CONCLUSIONS: Pattern
      electroretinography, cPLR and SD-OCT analysis are reproducible techniques, which
      can provide important information about retinal and optic nerve function and
      structure in mice.

PMID- 22642928
TI  - Lacrimal colic--an important ophthalmic symptom.
AB  - This concise case report introduces the novel concept of "lacrimal colic"-acute
      severe medial canthal pain resulting from sudden expansion of the lacrimal sac,
      commonly due to stone formation. The condition is compared with renal colic, in
      which a stone causes distension of the renal pelvis and similar severe pain. The
      case is presented with a concise literature review, and discussion on the
      relevance of the symptom in clinical practice.

PMID- 22642929
TI  - An extremely rare case of Merkel cell carcinoma metastasized to the duodenum.

PMID- 22642930
TI  - Intake of phytoestrogen foods and supplements among women recently diagnosed with
      breast cancer in Ontario, Canada.
AB  - Phytoestrogens are found in foods such as soy (isoflavones) and flaxseed
      (lignans), and certain botanical supplements. Their role in estrogen receptor
      positive (ER+) breast cancer recurrence and treatment is controversial, and it is
      unknown how this affects intake among patients. The Ontario Cancer Registry was
      used to identify 417 population-based breast cancer cases (mean time from
      diagnosis was 57 days). A questionnaire was mailed to determine intake of
      phytoestrogen foods and supplements in the last 2 mo, changes since diagnosis and
      differences by ER tumor status or hormonal treatment. Of 278 (67%) respondents,
      56% consumed soy foods, 39% consumed isoflavone-rich foods (tofu, soybeans, soy
      milk, soy nuts), and 70% ate lignan-rich foods, including flaxseed (33%). Only
      soy milk, flaxseed, and flaxseed bread were commonly consumed more than once/wk.
      Few patients (4%) took isoflavone (soy, red clover, kudzu, licorice, isoflavones)
      or lignan/flaxseed supplements. Since diagnosis, 17% started or stopped soy foods
      (most stopped); this was more prevalent among those receiving hormonal treatment
      (20%; 95% confidence interval (CI): 14, 26) than not (6%; 95% CI: 1, 12). No
      other differences by ER status or hormonal treatment were observed. Research is
      needed to confirm this and to explore influencing factors.

PMID- 22642932
TI  - Detection of JAK2 mutations in paraffin marrow biopsies by high resolution
      melting analysis: identification of L611S alone and in cis with V617F in
      polycythemia vera.
AB  - JAK2 mutations provide an objective major criterion for diagnosis of
      myeloproliferative neoplasms in the 2008 World Health Organization
      classification, and are particularly useful for cases of polycythemia vera (PV).
      High resolution melting analysis (HRM) using DNA from fresh samples for mutation
      detection in JAK2 exons 12 and 14 has been reported. Here, we describe two new
      HRM techniques that use both fresh and formalin-fixed paraffin-embedded marrow
      samples, allowing for both prospective and retrospective analyses. We used these
      novel assays to screen DNA isolated from paraffin-embedded marrow biopsies from
      104 patients with PV for mutations. HRM mutation-positive samples were
      subsequently sequenced. Ninety-seven samples (93.3%) were positive solely for the
      JAK2 p.V617F. One harbored a 33 bp duplication in exon 12 along with an exon 14
      p.V617F mutation, another had an exon 12 p.H538_K539delinsL, and a third carried
      a previously unreported mutation in PV, p.L611S, alone, and in cis with p.V617F.
      This indicates that these assays can detect known and novel JAK2 mutations in
      exons 12 and 14 using either fresh or paraffin-embedded archival materials.

PMID- 22642931
TI  - Stent elution rate determines drug deposition and receptor-mediated effects.
AB  - Drug eluting stent designs abound and yet the dependence of efficacy on drug dose
      and elution duration remains unclear. We examined these issues within a
      mathematical framework of arterial drug distribution and receptor binding
      following stent elution. Model predictions that tissue content linearly tracks
      stent elution rate were validated in porcine coronary artery sirolimus-eluting
      stents implants. Arterial content varied for stent types, progressively declining
      from its Day 1 peak and tracking with rate-limiting drug elution--near zero-order
      release was three-fold more efficient at depositing drug in the stented lesion
      than near first-order release. In vivo data were consistent with an overabundance
      of non-specific sirolimus-binding sites relative to the specific receptors and to
      the delivered dose. The implication is that the persistence time of receptor
      saturation and effect is more sensitive to duration of elution than to eluted
      amount. Consequently, the eluted amount should be sufficiently high to saturate
      receptors at the target lesion, but dose escalation alone is an inefficient
      strategy for prolonging the duration of sirolimus deposition. Moreover, receptor
      saturating drug doses are predicted to be most efficacious when eluted from
      stents in a constant zero order fashion as this maximizes the duration of elution
      and receptor saturation.

PMID- 22642933
TI  - Primary follicular lymphoma of the gastrointestinal tract: effect of stage,
      symptoms and treatment choice on outcome.

PMID- 22642934
TI  - Synergistic/additive interaction of valproic acid with bortezomib on
      proliferation and apoptosis of acute myeloid leukemia cells.
AB  - Resistance to chemotherapy is still a challenge for the treatment of acute
      myeloid leukemia. Combination use of histone deacetylase inhibitors (HDACIs) and
      proteasome inhibitors may provide a potential way to overcome drug resistance.
      One of the HDACIs, valproic acid (VPA), and a proteasome inhibitor, bortezomib
      (BOR), were assessed. Co-exposure of cells to VPA and BOR inhibited
      proliferation, arrested the cell cycle in G0-G1 phase and induced apoptosis in
      both HL60 and HL60A cells. These events were accompanied by the inhibition of
      cyclin D1 and human telomerase reverse transcriptase (hTERT) as well as
      telomerase activity. Moreover, synergism of proliferation inhibition was found in
      HL60A, superior to the additivity in HL60. The effects of combination treatment
      on cell cycle arrest and telomerase activity inhibition in HL60A were also more
      striking than those in HL60. In summary, our findings provide an insight into
      future clinical applications of the VPA-BOR combination regimen for AML,
      especially in those cases which are resistant to conventional chemotherapy.

PMID- 22642935
TI  - Incidence, predictors and significance of severe toxicity in patients with human
      immunodeficiency virus-associated Hodgkin lymphoma.
AB  - The incidence of Hodgkin lymphoma (HL) is rising among individuals infected with
      human immunodeficiency virus (HIV). Standard treatment regimens include
      vinblastine, which is known to cause neurotoxicity (NT) and is metabolized by
      cytochrome 3A4 (CYP3A4). This is inhibited by protease inhibitors (PIs), possibly
      increasing vinblastine exposure. There is little information on how interactions
      affect clinical outcome. A retrospective review of 32 patients with HIV-HL
      receiving chemotherapy with curative intent was performed to identify the
      frequency and risk factors for NT, hematologic toxicity (HT) and lung toxicity
      (LT). Treatment was: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in
      90%, MOPP/ABV (mechlorethamine, vincristine, procarbazine,
      prednisone/doxorubicin, bleomycin, vinblastine) in 10% and HAART (highly active
      anti-retroviral therapy) in 63%. Seventeen potential risk factors and 18
      individual anti-retroviral (ARV) agents were examined, and only ritonavir or
      lopinavir use was found to have a significant association with toxicity. Grade 3
      4 NT occurred in five patients, grade 3-4 HT in 17, infectious complications in
      10 and bleomycin LT in three. Ritonavir and lopinavir use was associated with
      grade 3-4 NT (p = 0.03 and p = 0.01, respectively), and ritonavir with any HT (p
      = 0.04). Patients with HIV-HL experienced an increased incidence of NT and
      possibly HT. The use of ritonavir or lopinavir was associated with NT, suggesting
      a clinically significant interaction with vinblastine. Prospective
      pharmacokinetic studies to devise a rational dosing strategy for vinblastine in
      patients receiving ritonavir/lopinavir are warranted.

PMID- 22642936
TI  - Outcome of patients with relapsed/refractory acquired immune deficiency syndrome
      related lymphoma diagnosed 1999-2008 and treated with curative intent in the AIDS
      Malignancy Consortium.
AB  - No comparative studies exist for relapsed/refractory (rel/rfr) acquired immune
      deficiency syndrome (AIDS)-related lymphoma (ARL). To determine practices over
      the last decade and to assess the outcomes of salvage chemotherapy with curative
      intent and autologous stem cell transplant (ASCT), we retrospectively evaluated
      treatment outcomes in patients with rel/rfr ARL who were treated in 13 national
      AIDS Malignancy Consortium (AMC) sites between 1999 and 2008 (n = 88). The most
      commonly used second-line therapies were ICE (ifosfamide/carboplatin/etoposide, n
      = 34), dose adjusted EPOCH
      (etoposide/prednisone/vincristine/cyclophosphamide/doxorubicin, n = 17) and ESHAP
      (etoposide/methylprednisolone/cytarabine/cisplatin, n = 11). The odds of
      achieving a response were lower for those with non-Hodgkin lymphoma (NHL) than
      for those with HL and for those with primary refractory disease than for those
      with relapse. Overall survival (OS) was significantly longer for those with
      relapsed disease compared to those with refractory disease and for those with non
      Burkitt NHL compared to those with Burkitt. OS was longer in patients who
      underwent ASCT compared to those who did not (1-year OS: 63.2% vs. 37.2%).
      However, among 32 patients (36%) who achieved a complete or partial response
      (CR/PR) after second-line therapy, 1-year OS was not different between the two
      groups (87.5% for ASCT vs. 81.8% for non-ASCT). Long-term survival in some
      patients with rel/rfr ARL may be possible without transplant, although transplant
      remains the standard of care for chemotherapy sensitive disease.

PMID- 22642937
TI  - Effect of tibolone and raloxifene on serum markers of apoptosis in postmenopausal
      women.
AB  - OBJECTIVES: To investigate the effect of tibolone and raloxifene on the serum
      apoptotic markers soluble Fas (sFas), soluble Fas ligand (sFasL) and cytochrome-c
      (cyt-c) in postmenopausal women. METHODS: A total of 89 healthy postmenopausal
      women, attending the University Menopause Clinic, were randomly allocated to
      tibolone (n =30), raloxifene (n =29) or no treatment (n =30). Serum apoptotic
      markers sFas, sFasL and cyt-c were measured at baseline and at 6 months. RESULTS:
      Serum sFasL decreased significantly in women receiving tibolone (baseline: 53.8+/
      28.3 pg/ml, 6 months: 40.45+/-19.2 pg/ml, p =0.001), whilst sFas levels did not
      significantly change in this group. Serum sFas or sFasL did not change either in
      the raloxifene group or in the control group. Serum cyt-c concentrations were
      under the detection limit of the assay in all women assessed. CONCLUSIONS:
      Tibolone use resulted in a significant decrease in serum sFasL, but not in serum
      sFas. Raloxifene had no effect on either sFas or sFasL. These results may
      indicate that tibolone use is associated with a decrease in receptor-mediated
      apoptosis.

PMID- 22642938
TI  - Metastatic rhabdomyosarcoma of the thyroid gland, a case report.
AB  - The thyroid gland is a known but an unusual site for metastatic tumors from
      various primary sites. Despite the fact that it is one of the largest vascular
      organs in the body, clinical and surgical cases have given an incidence of 3% of
      secondary malignances of the organ. Nevertheless, thyroid metastases are not an
      exceptional finding at autopsy, they are encountered in 2% to 24% of the patients
      with malignant neoplasm.Soft tissue sarcomas metastatic to the thyroid are
      extremely rare as the majority of thyroid metastasis are caused by tumors of the
      kidneys, lungs, mammary glands, ovaries , and colon or by melanomas.We report a
      case of 22-years-old woman with right leg rhabdomyosarcoma metastatic to the
      thyroid gland.

PMID- 22642939
TI  - Lifestyle and salivary cortisol at the age of 12 and 24 months.
AB  - AIM: To analyse salivary cortisol levels in 12- and 24-month-olds from families
      with an anthroposophic lifestyle and comparisons ('partly anthroposophic' and
      'non-anthroposophic'). METHODS: Salivary samples were collected at child ages of
      12 (n = 178) and 24 (n = 149) months. Cortisol was analysed with radioimmunoassay
      technique. RESULTS: Evening cortisol levels in children from anthroposophic
      families were lower than in comparisons at 12 months of age (geometric means:
      anthroposophic 1.7, partly anthroposophic 1.9, non-anthroposophic 3.6 nmol/L; p =
      0.024) and at 24 months of age (1.1, 1.8 and 2.9 nmol/L, respectively; p =
      0.002). At 24 months of age, similar differences were noted also for the
      afternoon levels (2.3, 3.3 and 3.9 nmol/L, respectively; p = 0.043). At age 12
      months, the differences in the evening cortisol were statistically explained by a
      meat-free diet and at age 24 months by the anthroposophic lifestyle as such. The
      circadian variations were parallel in the three groups at age 12 and 24 months.
      No cortisol differences were observed between parents representing different
      lifestyles. CONCLUSIONS: An anthroposophic lifestyle is associated with low
      cortisol levels in the evening at age 12 and 24 months, at age 24 months also in
      the afternoon.

PMID- 22642940
TI  - Internal carotid artery aneurysm presenting as orofacial pain.
AB  - OBJECTIVES: We report a case of an internal carotid artery aneurysm presenting as
      orofacial pain. METHOD: Case report and discussion. RESULTS: A 59-year-old
      patient presented with a four-year history of chronic oral pain accompanied by a
      right-sided occipital headache. No local organic pathology was detected, and a
      provisional diagnosis of persistent idiopathic facial pain was made. A
      neurosurgery referral was made to exclude neurovascular pathology, which resulted
      in the detection of an aneurysm originating from the right posterior
      communicating artery. This was successfully treated by coil embolisation, with
      subsequent resolution of symptoms. CONCLUSION: In this patient, an atypical
      history of pain with no other neurological signs or symptoms, other than
      accompanying occipital headache, led to the discovery of an intracranial
      aneurysm. This case highlights the need for appropriate referral and imaging in
      cases in which the clinical history and findings are not classical, and also
      emphasises the need for interdisciplinary management.

PMID- 22642941
TI  - Embracing additive manufacture: implications for foot and ankle orthosis design.
AB  - BACKGROUND: The design of foot and ankle orthoses is currently limited by the
      methods used to fabricate the devices, particularly in terms of geometric freedom
      and potential to include innovative new features. Additive manufacturing (AM)
      technologies, where objects are constructed via a series of sub-millimetre layers
      of a substrate material, may present the opportunity to overcome these
      limitations and allow novel devices to be produced that are highly personalised
      for the individual, both in terms of fit and functionality.Two novel devices, a
      foot orthosis (FO) designed to include adjustable elements to relieve pressure at
      the metatarsal heads, and an ankle foot orthosis (AFO) designed to have
      adjustable stiffness levels in the sagittal plane, were developed and fabricated
      using AM. The devices were then tested on a healthy participant to determine if
      the intended biomechanical modes of action were achieved. RESULTS: The
      adjustable, pressure relieving FO was found to be able to significantly reduce
      pressure under the targeted metatarsal heads. The AFO was shown to have distinct
      effects on ankle kinematics which could be varied by adjusting the stiffness
      level of the device. CONCLUSIONS: The results presented here demonstrate the
      potential design freedom made available by AM, and suggest that it may allow
      novel personalised orthotic devices to be produced which are beyond the current
      state of the art.

PMID- 22642943
TI  - How to define an area where transmission of arthropod-borne disease is occurring?

PMID- 22642942
TI  - Peripheral blood lymphocytes from low-grade squamous intraepithelial lesions
      patients recognize vaccine antigens in the presence of activated dendritic cells,
      and produced high levels of CD8 + IFNgamma + T cells and low levels of IL-2 when
      induced to proliferate.
AB  - BACKGROUND: Most infections with human papillomavirus (HPV) are resolved without
      clinical intervention, but a minority evolves into chronic lesions of distinct
      grades, including cervical-uterine cancer. It is known that in most cases the
      immune system mediates elimination of HPV infection. However, the mechanism of
      immune evasion leading to HPV persistence and development of early cervical
      lesions is not fully understood. The aim of the present work was to evaluate the
      potential of peripheral blood leukocytes (PBL) from low-grade squamous
      intraepithelial lesions (LSIL) patients to be activated ex-vivo by vaccine
      antigens, the participation of cytotoxic lymphocytes and regulatory T cells, and
      to determine the secretion of Th1 and Th2 cytokines mediated by stimulation of T
      cell receptors. RESULTS: We found that PBL from LSIL patients showed a
      significantly lower proliferation rate to vaccine antigens as compared to that of
      healthy donors, even though there was not a difference in the presence of
      antibodies to those antigens in sera from both groups. We did not find
      differences in either the frequency of CD4 + CD25 + FoxP3+ in PBL, or the levels
      of IL-4, IL-5 and IL-10 in plasma or conditioned media from PBL incubated with
      TcR agonists in vitro, between the two groups. However, we detected a lower
      production of IL-2 and a higher proportion of CD8 + IFNgamma + cells in PBL from
      LSIL patients as compared with PBL from normal donors. We also observed that PBL
      from patients infected by HPV-16 and -18 were not able to proliferate in the
      presence of soluble HPV antigens added to the culture; however, a high level of
      proliferation was attained when these antigens were presented by activated
      dendritic cells. CONCLUSIONS: Our results suggest that the immunodeficiency
      reported in LSIL patients could be due to the inability of specific cytotoxic T
      lymphocytes that for some unknown reason are present but unable to mount a
      response when challenged with their antigens, probably related to an in situ IL-2
      production deficiency.

PMID- 22642944
TI  - Re-emergence of dengue in Reunion, France, January to April 2012.
AB  - Since January 2012, 20 autochthonous cases of dengue virus (DENV) infection have
      been identified in Reunion. The first cases were detected on the western coast,
      but the two co-circulating viruses (DENV-1 and DENV-3) seemed to have spread
      later to different cities of the island. There is a non-negligible risk of
      increase in viral transmission over the following weeks, so health professionals
      and public health authorities in Reunion are preparing to face a potential
      epidemic.

PMID- 22642945
TI  - Epidemiological surveillance of West Nile neuroinvasive diseases in Italy, 2008
      to 2011.
AB  - We describe the geographical and temporal distribution of West Nile neuroinvasive
      diseases (WNND) cases in Italy from 2008 to 2011. The increasing number of
      confirmed human cases from eight in 2008 to 18 in 2009 and the occurrence of the
      virus in a larger geographical area in 2009 (moving from east to west) prompted
      the Ministry of Health to publish, in spring 2010, a national programme for WNND
      human surveillance, comprising veterinary and vector surveillance. Subsequently,
      in 2011, a new national plan on integrated human surveillance of imported and
      autochthonous vector-borne diseases (chikungunya, dengue and West Nile disease)
      was issued. Between 2008 and 2011, 43 cases of WNND were reported from five
      regions in Italy with a case fatality rate of 16%. The incidence of WNND during
      the entire study period was 0.55 per 100,000 population (range: 0.06-0.23 per
      100,000). During 2011, two new regions (Friuli-Venezia Giulia and Sardinia)
      reported confirmed cases in humans. Integrated human, entomological and animal
      surveillance for West Nile virus is a public health priority in Italy and will be
      maintained during 2012.

PMID- 22642946
TI  - WHO seeking input from health experts into ICD-11.

PMID- 22642947
TI  - WHO launches the World Health Statistics 2012.

PMID- 22642948
TI  - Mechanistic investigation of non-ideal sorption behavior in natural organic
      matter. 1. Vapor phase equilibrium.
AB  - Results from an experimental and modeling investigation of the influence of
      thermodynamic properties of highly purified natural organic matter (NOM) on
      observed equilibrium sorption/desorption behaviors of vapor phase
      trichloroethylene (TCE) is presented. Identification of glass transition (T(g))
      behavior in Leonardite humic acid and Organosolv lignin enabled evaluation of
      equilibrium and nonequilibrium sorption behavior in glassy and rubbery NOM.
      Specific differences in vapor phase equilibrium behavior in NOM above and below
      their T(g) were identified. In the glassy state (below T(g)), sorption of TCE is
      well-described by micropore models, with enthalpies of sorption characteristic of
      microporous, glassy macromolecules. Above T(g), sorptive behavior was well
      described by Flory-Huggins theory, indicating that the mobility and structural
      configuration of rubbery NOM materials may be analogous to the characteristic
      sorption behavior observed in more mobile, rubbery macromolecules, including
      strong entropic changes during sorption. Results from this work provide further
      support that, at least for the samples employed in this study, NOM possesses
      macromolecular characteristics which display sorption behavior similar to
      synthetic macromolecules-an important assumption in conceptual sorption
      equilibrium models used in the analysis of the fate and transport of VOCs in the
      environment.

PMID- 22642950
TI  - Wide field endoscopic resection for advanced colonic mucosal neoplasia: current
      status and future directions.
AB  - Most colonic adenomas are <= 10 mm and are routinely treated by colonoscopic
      polypectomy with long-term health benefits. Nonpolypoid lesions >= 20 mm, whether
      sessile or flat and laterally spreading, are forms of advanced mucosal neoplasia
      that cannot be managed by conventional polypectomy and are often referred for
      surgery. However, the majority of these lesions when carefully assessed are found
      to be noninvasive and can be safely and effectively treated by advanced
      endoscopic techniques including endoscopic mucosal resection or endoscopic
      submucosal dissection with resultant cost, morbidity, and mortality benefits.
      Lesion assessment is a critical component. Enhanced imaging methods provide the
      opportunity for accurate pathological characterization, informing treatment
      decisions, without the need for previous histologic confirmation. Techniques of
      advanced endoscopic resection are still in evolution and further improvements,
      including hybrid techniques, bringing less technically challenging and shorter
      procedures with superior safety can be reasonably expected in the next decade.
      Safety is a fundamental consideration. Methods of early recognition of
      complications, risk stratification, and management pathways are being developed
      and refined. Standardization, validation, and adoption of these technological
      developments will improve endoscopic interpretation and therapy and in
      combination with an increased understanding of adenoma molecular biology, will
      result in a progressively more individualized lesion-specific endoscopic
      approach. The future of advanced endoscopic resection in the colon is promising,
      and the next few years should see the boundaries of endoscopic resection expand
      well beyond the limits of what we know today.

PMID- 22642949
TI  - Interaction of nitrate and folate on the risk of breast cancer among
      postmenopausal women.
AB  - Ingested nitrate can be endogenously reduced to nitrite, which may form N-nitroso
      compounds, known potent carcinogens. However, some studies have reported no or
      inverse associations between dietary nitrate intake and cancer risk. These
      associations may be confounded by a protective effect of folate, which plays a
      vital role in DNA repair. We evaluated the interaction of dietary and water
      nitrate intake with total folate intake on breast cancer risk in the Iowa Women's
      Health Study. Dietary intake was assessed at study baseline. Nitrate intake from
      public water was assessed using a historical database on Iowa municipal water
      supplies. After baseline exclusions, 34,388 postmenopausal women and 2,875
      incident breast cancers were included. Overall, neither dietary nor water nitrate
      was associated with breast cancer risk. Among those with folate intake >=400
      MUg/day, breast cancer risk was significantly increased in public water users
      with the highest nitrate quintile (HR = 1.40, 95% CI = 1.05-1.87) and private
      well users (HR = 1.38, 95% CI = 1.05-1.82) compared to public water users with
      the lowest nitrate quintile; in contrast, there was no association among those
      with lower folate intake. Our findings do not support a previous report of
      increased risk of breast cancer among individuals with high dietary nitrate but
      low folate intake.

PMID- 22642951
TI  - Robot-assisted endoscopic submucosal dissection is effective in treating patients
      with early-stage gastric neoplasia.
AB  - BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a new technique for
      endoscopic resection of early-stage gastrointestinal cancers. Though ESD achieves
      high rate of en bloc resection, it is technically difficult to master. The
      development of a novel robotic endoscopic system that has 2 arms attached to an
      ordinary endoscope-Master and Slave Transluminal Endoscopic Robot (MASTER)-has
      improved the performance of complex endoluminal procedures. We evaluated the
      efficacy of MASTER-assisted ESD in treatment of patients with early-stage gastric
      neoplasia. METHODS: We performed a multicenter prospective study of 5 patients
      with early-stage gastric neoplasia, limited to the mucosa. After markings and
      circumferential mucosal incision, all submucosal dissections were performed using
      the MASTER system. We measured baseline demographics, tumor characteristics, and
      perioperative and clinical outcomes. RESULTS: All patients underwent successful
      MASTER-assisted ESD. The mean submucosal dissection time was 18.6 minutes
      (median, 16 minutes; range, 3-50 minutes). No perioperative complications were
      encountered. Three patients were discharged from the hospital within 12 hours and
      2 on the third day after the procedures. Two patients were found to have
      intramucosal adenocarcinoma, 1 had high-grade dysplasia, 1 had low-grade
      dysplasia, and 1 had a hyperplastic polyp. The resection margins were clear of
      tumors in all 5 patients. No complications were observed at the 30-day follow-up
      examination. Follow-up endoscopic examinations revealed that none of the patients
      had residual or recurrent tumors. CONCLUSIONS: A flexible endoscopy robotic
      system can be used to perform ESD and effectively treat patients with early
      gastric neoplasia.

PMID- 22642953
TI  - Balloon dilation with adequate duration is safer than sphincterotomy for
      extracting bile duct stones: a systematic review and meta-analyses.
AB  - BACKGROUND & AIMS: Endoscopic sphincterotomy (EST) is the standard treatment for
      choledocholithiasis. Endoscopic papillary balloon dilation (EPBD) has a lower
      risk for bleeding than EST, but EPBD is reserved for patients with bleeding
      diathesis because some studies reported that it increases the risk for
      pancreatitis. A short dilation time (<=1 minute) is therefore recommended to
      reduce pancreatitis. However, there is evidence for an inverse relationship
      between EPBD duration and pancreatitis, prompting reevaluation of the optimal
      duration and relative safety of EPBD vs EST. METHODS: We systematically reviewed
      randomized controlled trials to compare long EPBD (>1 minute), short EPBD (<=1
      minute), and EST regarding pancreatitis and overall complications. In addition to
      pairwise meta-analyses, Bayesian network meta-analysis was undertaken to compare
      the 3 procedures together. Relation between duration and outcome was also
      analyzed by meta-regression. RESULTS: Compared with EST, short EPBD had a higher
      risk for pancreatitis (odds ratio [OR] by traditional analysis, 3.87; 95%
      confidence interval, 1.08-13.84 and OR by network meta-analysis, 4.14; 95%
      credible interval, 1.58-12.56), but long EPBD did not pose a higher risk than EST
      (1.14, 0.56-2.35 and 1.07, 0.38-2.76). Long EPBD had a lower overall rate of
      complications than EST (0.61, 0.36-1.04 and 0.54, 0.20-1.36). In network meta
      analysis, probabilities of being the safest treatment for long EPBD/short
      EPBD/EST regarding pancreatitis and overall complications were 43.9%/0.2%/55.9%
      and 90.3%/1.3%/8.4%, respectively. CONCLUSIONS: Duration of EPBD is inversely
      associated with pancreatitis risk. Currently recommended <=1-minute dilation
      actually increases pancreatitis. EPBD with adequate duration may be preferred
      over EST because of comparable pancreatitis but lower overall complication rates.

PMID- 22642954
TI  - Hepatic amyloidosis presenting as a large hepatic mass.

PMID- 22642955
TI  - In-hospital mortality and economic burden associated with hepatic encephalopathy
      in the United States from 2005 to 2009.
AB  - BACKGROUND & AIMS: Hepatic encephalopathy (HE) is a major complication of
      cirrhosis that causes substantial mortality and utilization of resources.
      METHODS: We analyzed 5 cycles of the Nationwide Inpatient Sample, conducted
      between 2005 and 2009, to determine national estimates of incidence, prevalence,
      inpatient mortality, severity of illness, and resource utilization for inpatients
      with HE. RESULTS: The yearly inpatient incidence of HE ranged from 20,918 (2005)
      to 22,931 (2009) (P = .2226), comprising approximately 0.33% of all
      hospitalizations in the United States. Over the 5-year period of analysis,
      mortality of inpatients with HE remained relatively stable, at 14.13%-15.61% (P =
      .062); however, the proportion of patients with major and extreme severity of
      illness increased (P < .0001). The average length of inpatient stay increased
      from 8.1 to 8.5 days (P = .019). The average total inpatient charges increased
      from $46,663 to $63,108 per case (P < .0001). Furthermore, total national charges
      related to HE increased from $4676.7 million (2005) to $7244.7 million (2009). In
      multivariate analysis, independent predictors of inpatient mortality included the
      number of diagnoses per admission (odds ratio [OR] = 1.022; 95% confidence
      interval [CI], 1.016-1.029 per diagnosis), number of procedures per admission (OR
      = 1.192 per procedure; 95% CI, 1.177-1.208), and major or extreme severity of
      illness (OR = 3.16; 95% CI, 2.84-3.50). The most important predictors of cost,
      charge, and length of stay were admission to a large, urban hospital; use of
      Medicaid or Medicaid as the payer; major or extreme severity of illness; number
      of diagnoses at discharge; and procedures per admission (P < .05). CONCLUSIONS:
      Resource utilization increased from 2005 to 2009 for patients discharged from US
      hospitals with the diagnosis of HE. The inpatient mortality rate, however,
      remained stable, despite a trend toward more severe disease.

PMID- 22642956
TI  - Use of direct, endoscopic-guided measurements of mucosal impedance in diagnosis
      of gastroesophageal reflux disease.
AB  - BACKGROUND & AIMS: Diagnostic tests for gastroesophageal reflux disease (GERD)
      are constrained because measurements are made at a single time point, so the long
      term effects on the mucosa cannot be determined. We developed a minimally
      invasive system to assess changes in esophageal mucosal impedance (MI), a marker
      of reflux. We measured the extent of changes in MI along the esophagus and show
      that the device to assess MI can be used to diagnose patients with GERD. METHODS:
      A single-channel MI catheter composed of a unique sensor array was designed to
      easily traverse the working channel of an upper endoscope. We performed a
      prospective longitudinal study of patients with erosive esophagitis (n = 19),
      nonerosive but pH-positive GERD (n = 23), and those without GERD (n = 27). MI was
      measured at the site of esophagitis as well as 2, 5, and 10 cm above the
      squamocolumnar junction. The MI values were compared among groups, at different
      levels along the esophageal axis. RESULTS: Median MI values were significantly
      lower at the site of erosive mucosa (811 Omega; range, 621-1272 Omega) than other
      nonerosive regions (3723 Omega; range, 2421-4671 Omega; P = .001), and were
      significantly lower at 2 cm above the squamocolumnar junction in patients with
      GERD (2096 Omega; range, 1415-2808 Omega), compared with those without GERD (3607
      Omega; range, 1973-4238 Omega; P = .008). There was a significant and graded
      increase in MI along the axis of the distal to proximal esophagus in patients
      with GERD that was not observed in individuals without reflux (P = .004).
      CONCLUSIONS: Measurements of MI along the esophagus can be used to identify
      patients with GERD. ClinicalTrials.gov, number NCT01194323.

PMID- 22642957
TI  - Effects of dropping the requirement for goblet cells from the diagnosis of
      Barrett's esophagus.
AB  - BACKGROUND & AIMS: The 2011 American Gastroenterological Association diagnostic
      criteria for Barrett's esophagus (BE) require the presence of goblet cells in
      biopsy specimens of columnar mucosa within the esophagus. In other countries,
      patients can be diagnosed with BE based on evidence of columnar epithelium,
      regardless of the presence of goblet cells. We examined the effects that a
      broader criteria would have on diagnoses of patients with endoscopically
      suspected BE. We also compared the clinical outcomes of patients with and without
      goblet cells in esophageal biopsy samples. METHODS: We analyzed the University of
      Chicago Medical Center database to identify 690 patients with no previous history
      of BE who underwent endoscopic biopsy analysis for BE from 1987 to 2008. We
      collected endoscopy reports, histology results, and chart reviews. RESULTS: Of
      biopsy specimens analyzed, samples from 258 patients contained goblet cells and
      379 did not (53 of the biopsy samples contained only squamous mucosa). Patients
      whose biopsy samples contained goblet cells had longer endoscopic columnar
      segments (mean, 4.6 cm) and more biopsy specimens taken (mean, 5 biopsy
      specimens) than those without (mean length, 1.6 cm; mean, 4 biopsy specimens). Of
      patients whose biopsy specimens did not contain goblet cells, 35% underwent
      additional endoscopy; goblet cells continued to be absent in 88% of these (mean
      follow-up time, 5.8 y; 2.8 additional procedures; mean total biopsy specimens,
      12). Goblet cells were identified in only 19% of all patients with columnar
      mucosa less than 2 cm. No patient without goblet cells developed adenocarcinoma.
      CONCLUSIONS: Decreasing the requirement for goblet cells would increase the
      diagnosis of BE by 147%. Among patients with short columnar segments, subsequent
      endoscopy generally does not reveal goblet cells, so the columnar mucosa might
      represent proximal stomach. Decreasing the requirement for goblet cells would
      cause many patients to be inaccurately labeled as BE.

PMID- 22642958
TI  - Chronic pancreatitis: making the diagnosis.

PMID- 22642959
TI  - The relationship between cognition and sensation in determining when and where to
      void: the concept of cognitive voiding.
AB  - Study Type--Aetiology (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? The factors taken into consideration when
      determining when and where to void are poorly understood. Studies on bladder
      sensations, obtained during cystometry of from voiding diaries, are proving
      difficult to transfer to everyday experiences. There is therefore a need to
      explore what does influence when and where to void. This study, using focus
      groups, highlights the fact that many voids are driven by behavioural factors not
      by sensations of desire or need to void. It is further noted that a key factor in
      the final decision to void is an awareness of bladder volume. The concepts of
      'cognitive voiding' informed by 'bladder awareness' are introduced and, if
      correct, will influence the way studies are devised and interpreted to explore
      lower urinary tract dysfunction and pharmacotherapy. OBJECTIVE * To investigate
      the inter-relationship between conscious decision-making processes and bladder
      sensation in determining the need, time and place to void SUBJECTS AND METHODS: *
      The approach used interview focus groups and qualitative thematic analysis. In
      this preliminary study, 25 women were included (aged 21-90 years) meeting in
      groups of one to five on four occasions. RESULTS: * The thematic analysis yielded
      six themes: temporal and cognitive maps, risk issues, habituation and
      opportunistic behaviour and awareness of the bladder. * For most voids, the
      decision to void was not based on sensation but determined by multiple factors:
      personal knowledge of time of last void, anticipated time to next void, proximity
      of toilets, a risk assessment or habituated behaviour. * As the bladder filled
      the subjects described an increasing awareness of their bladder. Such sensations
      were not immediately associated with desire to void. Rather, these sensations
      were described as influencing the cognitive processes of considering when and
      where to void. * A sub-group of subjects reported little awareness as their
      bladder filled, experiencing only sudden strong sensations that needed immediate
      action for fear of leakage. CONCLUSIONS: * The decision to void is primarily a
      cognitive process influenced by multiple elements of which bladder awareness is
      only one. * Mechanisms generating awareness may be intensified or lost reflecting
      possible different pathological states. The importance of these observations in
      relation to current views of normal and abnormal voiding is discussed.

PMID- 22642960
TI  - Building a transnational biosurveillance network using semantic web technologies:
      requirements, design, and preliminary evaluation.
AB  - BACKGROUND: Antimicrobial resistance has reached globally alarming levels and is
      becoming a major public health threat. Lack of efficacious antimicrobial
      resistance surveillance systems was identified as one of the causes of increasing
      resistance, due to the lag time between new resistances and alerts to care
      providers. Several initiatives to track drug resistance evolution have been
      developed. However, no effective real-time and source-independent antimicrobial
      resistance monitoring system is available publicly. OBJECTIVE: To design and
      implement an architecture that can provide real-time and source-independent
      antimicrobial resistance monitoring to support transnational resistance
      surveillance. In particular, we investigated the use of a Semantic Web-based
      model to foster integration and interoperability of interinstitutional and cross
      border microbiology laboratory databases. METHODS: Following the agile software
      development methodology, we derived the main requirements needed for effective
      antimicrobial resistance monitoring, from which we proposed a decentralized
      monitoring architecture based on the Semantic Web stack. The architecture uses an
      ontology-driven approach to promote the integration of a network of sentinel
      hospitals or laboratories. Local databases are wrapped into semantic data
      repositories that automatically expose local computing-formalized laboratory
      information in the Web. A central source mediator, based on local reasoning,
      coordinates the access to the semantic end points. On the user side, a user
      friendly Web interface provides access and graphical visualization to the
      integrated views. RESULTS: We designed and implemented the online Antimicrobial
      Resistance Trend Monitoring System (ARTEMIS) in a pilot network of seven European
      health care institutions sharing 70+ million triples of information about drug
      resistance and consumption. Evaluation of the computing performance of the
      mediator demonstrated that, on average, query response time was a few seconds
      (mean 4.3, SD 0.1 * 10(2) seconds). Clinical pertinence assessment showed that
      resistance trends automatically calculated by ARTEMIS had a strong positive
      correlation with the European Antimicrobial Resistance Surveillance Network (EARS
      Net) (rho = .86, P < .001) and the Sentinel Surveillance of Antibiotic Resistance
      in Switzerland (SEARCH) (rho = .84, P < .001) systems. Furthermore, mean
      resistance rates extracted by ARTEMIS were not significantly different from those
      of either EARS-Net (? = +/-0.130; 95% confidence interval -0 to 0.030; P < .001)
      or SEARCH (? = +/-0.042; 95% confidence interval -0.004 to 0.028; P = .004).
      CONCLUSIONS: We introduce a distributed monitoring architecture that can be used
      to build transnational antimicrobial resistance surveillance networks. Results
      indicated that the Semantic Web-based approach provided an efficient and reliable
      solution for development of eHealth architectures that enable online
      antimicrobial resistance monitoring from heterogeneous data sources. In future,
      we expect that more health care institutions can join the ARTEMIS network so that
      it can provide a large European and wider biosurveillance network that can be
      used to detect emerging bacterial resistance in a multinational context and
      support public health actions.

PMID- 22642961
TI  - The role of brain-derived neurotrophic factor (BDNF) gene variants in
      antipsychotic response and antipsychotic-induced weight gain.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) has extensive effects on the
      nervous system including cell survival, differentiation, neuronal growth and
      maintenance, as well as cell death. Moreover, it promotes synaptic plasticity and
      interacts with dopaminergic and serotonergic neurons, suggesting an important
      role on the alteration of brain function with antipsychotic medications and
      induced weight gain in schizophrenia patients. The differential effects of BDNF
      gene variants could lead to changes in brain circuitry that would in turn cause
      variable response to antipsychotic medication. Therefore, we hypothesized that
      genetic variation in this candidate gene helps in explaining the inter-individual
      variation observed in antipsychotic drug treatment with respect to response and
      induced weight gain. METHOD: We examined four single-nucleotide polymorphisms
      across the BDNF gene, including Val66Met (rs6265). Prospective BPRS change scores
      and weight change after six weeks were obtained from a total of 257 schizophrenia
      patients of European ancestry. RESULTS: The markers rs11030104 and Val66Met were
      associated with antipsychotic response (P=0.04; 0.007, respectively). On the
      other hand, marker rs1519480 was associated with weight gain (P=0.04). Moreover,
      a two-marker haplotype across rs6265 and rs1519480 was associated with weight
      change (P=0.001). Results with Val66Met in response, and results with rs6265
      rs1519480 haplotypes remained significant at the modified Bonferroni corrected
      alpha of 0.017. CONCLUSION: BDNF genetic variants might play an important role in
      predicting antipsychotic response and antipsychotic-induced weight gain. However,
      replication in larger and independent samples is required.

PMID- 22642962
TI  - Feeding styles and child weight status among recent immigrant mother-child dyads.
AB  - BACKGROUND: Research has shown that parental feeding styles may influence
      children's food consumption, energy intake, and ultimately, weight status. We
      examine this relationship, among recent immigrants to the US. Given that
      immigrant parents and children are at greater risk for becoming overweight/obese
      with increased time in the US, identification of risk factors for weight gain is
      critical. METHODS: Baseline data was collected on 383 mother-child dyads enrolled
      in Live Well, a community-based, participatory, randomized controlled lifestyle
      intervention to prevent weight gain in recent immigrant mothers. Socio
      demographic information together with heights and weights were collected for both
      mother and child. Acculturation, behavioral data, and responses to the
      Caregiver's Feeding Styles Questionnaire (CFSQ) were also obtained from the
      mother. RESULTS: The children's average age was 6.2 +/- 2.7 years, 58% male.
      Mothers had been in the country for an average of 6.0 +/- 3.3 years, and are
      Brazilian (36%), Haitian (34%) and Latino (30%). Seventy-two percent of the
      mothers were overweight/obese, while 43% of the children were overweight/obese.
      Fifteen percent of mothers reported their feeding style as being high
      demanding/high responsive; 32% as being high demanding/low responsive; 34% as
      being low demanding/high responsive and 18% as being low demanding/low
      responsive. In bivariate analyses, feeding styles significantly differed by child
      BMIz-score, ethnic group, and mother's perceived stress. In multiple linear
      regression, a low demanding/high responsive feeding style was found to be
      positively associated (beta = 0.56) with a higher child weight as compared to
      high demanding/high responsive, controlling for known covariates (p = 0.01).
      CONCLUSIONS: Most mothers report having a low demanding/high responsive feeding
      style, which is associated with higher child weight status in this diverse
      immigrant population. This finding adds to the growing literature that suggests
      this type of feeding style may be a risk factor for childhood obesity. Further
      research is needed to help understand the larger socio-cultural context and its
      influence on feeding dynamics among immigrant families and families of lower
      incomes. How parents establish a certain feeding style in their home country
      compared to when they move to the US "obesogenic" environment, should also be
      explored.

PMID- 22642963
TI  - Cervical and breast cancer-screening knowledge of women with developmental
      disabilities.
AB  - Women with developmental disabilities are significantly less likely than women
      without disabilities to receive cervical and breast cancer screening according to
      clinical guidelines. The reasons for this gap are not understood. The present
      study examined the extent of women's knowledge about cervical and breast cancer
      screening, with the intention of informing the development and testing of
      interventions to increase cervical and breast cancer screening rates for these
      women. In a sample of 202 community-dwelling women with developmental
      disabilities, most women had little knowledge of cervical and breast cancer
      screening. Women who were living at home with family caregivers had the most
      limited understanding of cervical and breast cancer screening. Policy and
      practice implications are discussed.

PMID- 22642964
TI  - Demographic characteristics, health conditions, and residential service use in
      adults with Down syndrome in 25 U.S. states.
AB  - This study describes service users with Down syndrome (N = 1,199) and a
      comparative sample with intellectual and developmental disabilities but not Down
      syndrome (N = 11,182), drawn from National Core Indicator surveys of adult
      service users in 25 U.S. states. Individuals with Down syndrome were younger than
      were individuals without Down syndrome. Men with Down syndrome were older than
      women with Down syndrome, whereas the reverse was true of the individuals without
      Down syndrome. Most (68%) people with Down syndrome had mild or moderate
      intellectual disability. The prevalence of vision impairment, hearing impairment,
      and physical disability increased with age. Adults with Down syndrome were more
      likely to have Alzheimer's dementia, have a hearing impairment, or be overweight,
      but they were less likely to have a physical disability than those without Down
      syndrome. Adults with Down syndrome were less likely to live in institutions or
      their own home, but they more likely to live in a family member's home. The
      results of a logistic regression showed that participants were more likely to be
      reported to be overweight if they had Down syndrome, were female, and were
      physically inactive, but they were less likely to be reported to be overweight if
      they were older, had more severe intellectual disability, had cerebral palsy, or
      were not independently mobile.

PMID- 22642965
TI  - Physical activity patterns of youth with Down syndrome.
AB  - The purpose of this study was to examine the physical activity patterns of
      children with Down syndrome. A cross-sectional approach and accelerometry were
      used to measure the time children with Down syndrome (N = 104) spent in
      sedentary, light, and moderate-to-vigorous physical activity. Results indicated
      that adolescents from ages 14 to 15 years were the most sedentary and spent the
      least amount of time in light and moderate-to-vigorous physical activity. A
      general trend of decreasing physical activity as children increase in age was
      found. This trend is similar to that found among typically developing youth.
      Participants in this study were found to spend a majority of their day engaged in
      sedentary activities. Results indicate that most participants were not
      accumulating the recommended 60 minutes of moderate or vigorous physical
      activity.

PMID- 22642966
TI  - Normal for an Asperger: notions of the meanings of diagnoses among adults with
      Asperger syndrome.
AB  - This study explores the production of a counterhegemonic discourse of "autistic
      normalcy" among adults with high-functioning autism by analyzing notions of
      diagnosis. The discourse analyses are based on material from ethnographic
      fieldwork in a Swedish educational setting. Study participants were 3 male and 9
      female adults who had been diagnosed with Asperger syndrome. The notion of
      diagnosis comprises issues concerning coming out and knowledge production. The
      findings capture an ongoing reformulation process among people involved in the
      autistic self-advocacy movement when it comes to the meanings of Asperger
      syndrome and what it means to be a person with Asperger syndrome.

PMID- 22642967
TI  - Transformation through health teaching for adults with intellectual and
      developmental disabilities: a qualitative study.
AB  - Adults with intellectual and developmental disabilities have medical conditions
      similar to those among the general population but with more complex presentation,
      a extended life expectancy, and increased risk of morbidity and mortality. These
      adults' health education has been inadequate. In this qualitative study, the
      author describes the experiences of 23 registered nurses who provide health
      teaching to adults with intellectual and developmental disabilities, selection of
      and health topics taught, and teaching activities put into practice. The author
      used a rigorous descriptive, naturalistic inquiry design with purposive (n = 22)
      and snowball (n = 1) sampling. Data were gathered through individual interviews,
      focus groups, and nonparticipant observations, and analyzed with a constant
      comparative method. Findings concerned the educators' developmental process, use
      of a social context to teach, and health-teaching activities. Registered nurses s
      described their transformation from insecure, novice health educators to
      confident and passionate educators of adults with intellectual and developmental
      disabilities. Findings apply to multiple disciplines.

PMID- 22642968
TI  - Sexuality and sex education of adolescents with intellectual disability: mothers'
      attitudes, experiences, and support needs.
AB  - Few studies have considered families' views about adolescents' sexual
      development. The authors compared attitudes and behaviors of mothers of young
      people with (n = 30) and without intellectual disability (n = 30). Both groups
      placed similar importance on dealing with their children's developing sexuality
      and were similarly confident in doing so. Mothers of young people with
      intellectual disability held more cautious attitudes about contraception,
      readiness to learn about sex, and decisions about intimate relationships. Mothers
      expressed concerns about their children with intellectual disability and sexual
      vulnerability. They had also spoken about fewer sexual topics with their children
      and began these discussions when their children were older. The findings can
      inform more sensitive supports and materials to help families deal with the
      sexual development of their offspring.

PMID- 22642969
TI  - Sex and genes, part 1: sexuality and Down, Prader-Willi, and Williams syndromes.
AB  - Specific genetic syndromes affect individuals' sexual development, experiences,
      and fertility. Individuals with specific syndromes can also display inappropriate
      sexual behavior resulting from vulnerabilities presented by their genetic makeup.
      Using clinical case studies, we discuss the specific impact that Down, Prader
      Willi, and Williams syndromes can have on sexual development and behavior.
      Applying a biopsychosocial approach, we present the primary sexual effects, such
      as delayed sexual development and infertility. These genetic syndromes are also
      associated with challenges that are not specifically sexual in nature but that
      affect sexual expression, such as self-injury, mental health issues, or epilepsy.
      Medication side effects are also discussed. We conclude with treatment
      recommendations for individuals with sexual challenges, considering the unique
      effects of these three syndromes on sexuality.

PMID- 22642970
TI  - Who was Deborah Kallikak?
AB  - The Kallikak Family was, along with The Jukes: A Study in Crime, Pauperism,
      Disease, and Heredity, one of the most visible eugenic family narratives
      published in the early 20th century. Published in 1912 and authored by
      psychologist Henry Herbert Goddard, director of the psychological laboratory at
      the Vineland Training School for Feebleminded Children in Vineland, New Jersey,
      The Kallikak Family told the tale of a supposedly "degenerate" family from rural
      New Jersey, beginning with Deborah, one of the inmates at the Training School.
      Like most publications in the genre, this pseudoscientific treatise described
      generations of illiterate, poor, and purportedly immoral Kallikak family members
      who were chronically unemployed, supposedly feebleminded, criminal, and, in
      general, perceived as threats to "racial hygiene." Presented as a "natural
      experiment" in human heredity, this text served to support eugenic activities
      through much of the first half of the 20th century. This article reviews the
      story of Deborah Kallikak, including her true identity, and provides evidence
      that Goddard's treatise was incorrect.

PMID- 22642972
TI  - Increase in MMP-2 activity in overweight and obese women is associated with
      menopausal status.
AB  - BACKGROUND: Metalloproteinases (MMPs) are synthesized in the subendothelium and
      are involved in the atherosclerosis and cardiovascular disease process because of
      their major significance in vascular remodeling and plaque rupture. MMPs are also
      synthesized in adipose tissue during angiogenesis; however, the role of these
      enzymes in obesity and insulin-resistant states is still controversial.
      OBJECTIVE: To evaluate MMP-2 activity in the circulation of overweight and obese
      women and in normal-weight controls, and to associate the levels of these factors
      with metabolic, adipose tissue and inflammation biomarkers. METHODS: Plasma MMP-2
      activity, adiponectin and C-reactive protein concentration, lipoprotein profile
      and HOMA were determined in 39 healthy women (13 normal weight and 26
      overweight/obese). RESULTS: Overweight/obese women were older (p < 0.001) than
      normal-weight women; 20/26 of overweight/obese women were postmenopausal compared
      with 4/13 of normal-weight women. Overweight/obese women had significantly higher
      plasma activity of MMP-2 than controls (mean relative area: 0.81 (range 0.4-1.92)
      vs. 1.33 (range 0.4-3.1); p < 0.005); this difference was lost after adjusting
      for menopausal status. MMP-2 activity positively correlated with waist
      circumference (p < 0.002), HOMA (p < 0.003), and high-sensitivity C-reactive
      protein (p < 0.05), apolipoprotein B (p = 0.006) and triglyceride/high density
      lipoprotein (HDL) cholesterol index (p < 0.001), and negatively with HDL
      cholesterol (p < 0.001), HDL2 cholesterol (p < 0.008), HDL3 cholesterol (p <
      0.05) and adiponectin (p < 0.05). The association with HOMA and adiponectin
      persisted even after adjusting for menopausal status. CONCLUSION: Our finding of
      increased plasma activity of MMP-2 in overweight/obese women, associated with
      menopausal status, is important given that it fits in with an early stage of
      cardiovascular disease; the association of MMP-2 activity with obesity markers
      may be a link between adipose tissue and risk for cardiovascular disease.

PMID- 22642973
TI  - The prevalence, patterns and predictors of diabetic peripheral neuropathy in a
      developing country.
AB  - Prevalence of diabetes mellitus (DM) has reached epidemic proportions in Sri
      Lanka. Presently there are studies on the community prevalence of distal
      peripheral neuropathy (DPN) in Sri Lanka. We describe prevalence, patterns and
      predictors of DPN in patients with DM in Sri Lanka. Data were collected as part
      of a national study on DM. In new cases DPN was assessed using the Diabetic
      Neuropathy-Symptom (DNS) score, while in those with established diabetes both DNS
      and Toronto-Clinical-Scoring-System (TCSS) were used. A binary logistic
      regression analysis was performed with 'presence of DPN' as the dichomatous
      dependent variable and other independent co-variants. The study included 528
      diabetic patients (191-new cases), with a mean age of 55.0 +/- 12.4 years and
      37.3% were males, while 18% were from urban areas. Prevalence of DPN according to
      DNS score among all patients, patients with already established diabetes and
      newly diagnosed patients were 48.1%, 59.1% and 28.8% respectively. Prevalence of
      DPN in those with established DM as assessed by TCSS was 24% and the majority had
      mild DPN (16.6%). The remainder of the abstract is based on subjects with
      established DM. The prevalence of DPN in males and female was 20.0% and 26.4%
      respectively. The mean age of those with and without DPN was 62.1 +/- 10.8 and
      55.1 +/- 10.8 years respectively (p < 0.001). The majority of those with DPN were
      from rural-areas (75.3%) and earned a monthly income < Sri Lankan Rupees 12,000
      (87.6%). In the binary logistic-regression presence of foot ulcers (OR:10.4;
      95%CI 1.8-16.7), female gender (OR:6.7; 95%CI 2.0-9.8) and smoking (OR:5.9; 95%CI
      1.4-9.7) were the strongest predictors followed by insulin treatment (OR:4.3;
      95%CI 1.3-6.9), diabetic retinopathy (OR:2.7; 95%CI 1.3-5.4), treatment with
      sulphonylureas (OR:1.8; 95%CI 1.1-3.2), increasing height (OR:1.8; 95%CI 1.2
      2.4), rural residence (OR:1.8; 95%CI 1.1-2.5), higher levels of triglycerides
      (OR:1.6; 95%CI 1.2-2.0) and longer duration of DM (OR:1.2; 95%CI 1.1-1.3). There
      is a high prevalence of DPN among Sri Lankan adults with diabetes. The study
      defines the impact of previously known risk factors for development of DPN and
      identifies several new potential risk factors in an ethnically different large
      subpopulation with DM.

PMID- 22642974
TI  - Unusual, pH-induced, self-assembly of sophorolipid biosurfactants.
AB  - An increasing need exists for simple, bioderived, nontoxic, and up-scalable
      compounds with stimuli-responsive properties. Acidic sophorolipids (SL) are
      glucose-based biosurfactants derived from the yeast broth of Candida bombicola
      (teleomorph: Starmerella bombicola). The specific design of this molecule, a
      sophorose head with a free end-COOH group at the end of the alkyl chain, makes it
      a potentially interesting pH-responsive compound. We have specifically
      investigated this assumption using a combination of small angle neutron
      scattering (SANS), transmission electron microscopy under cryogenic conditions
      (Cryo-TEM), and nuclear magnetic resonance (NMR) techniques and found a strong
      dependence of SL self-assembly on the degree of ionization, alpha, of the COOH
      group at concentration values as low as 5 and 0.5 wt %. At least three regimes
      can be identified where the supramolecular behavior of SL is unexpectedly
      different: (1) at low alpha values, self-assembly is driven by concentration, C,
      and micelles are mainly identified as nonionic objects whose curvature decreases
      (sphere-to-rod) with C; (2) at mid alpha values, the formation of COO(-) groups
      introduces negative charges at the micellar surface inducing an increase in
      curvature (rod-to-sphere transition). Repulsive electrostatic long-range
      interactions appear at this stage. In both regimes 1 and 2, the cross-section
      radius of the micelles is below 25 A. This behavior is concentration independent.
      (3) At alpha = 1, individual micelles seem to favor the formation of large
      netlike tubular aggregates whose size is above 100 nm. Such a complex behavior is
      very unique as it is generally not observed for common alkyl-based surfactants in
      concentration ranges below 5-10 wt %.

PMID- 22642976
TI  - miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase
      regulator, in prostate cancer.
AB  - BACKGROUND: Prognosis of prostate cancer (PCa) is based mainly in histological
      aspects together with PSA serum levels that not always reflect the real
      aggressive potential of the neoplasia. The micro RNA (miRNA) mir-21 has been
      shown to regulate invasiveness in cancer through translational repression of the
      Metaloproteinase (MMP) inhibitor RECK. Our aim is to investigate the levels of
      expression of RECK and miR-21 in PCa comparing with classical prognostic factors
      and disease outcome and also test if RECK is a target of miR-21 in in vitro study
      using PCa cell line. MATERIALS AND METHODS: To determine if RECK is a target of
      miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU
      145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK
      expression levels in PCa samples we performed quantitative real-time polymerase
      chain reaction (qRT-PCR). RESULTS: The in vitro assays showed a decrease in
      expression levels of RECK after transfection with pre-miR-21, and an increase of
      MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We
      defined three profiles to compare the prognostic factors. The first was
      characterized by miR-21 and RECK underexpression (N = 25) the second was
      characterized by miR-21 overexpression and RECK underexpression (N = 12), and the
      third was characterized by miR-21 underexpression and RECK overexpression (N =
      16). From men who presented the second profile (miR-21 overexpression and RECK
      underexpression) 91.7% were staged pT3. For the other two groups 48.0%, and 46.7%
      of patients were staged pT3 (p = 0.025). CONCLUSIONS: Our results demonstrate
      RECK as a target of miR-21. We believe that miR-21 may be important in PCa
      progression through its regulation of RECK, a known regulator of tumor cell
      invasion.

PMID- 22642975
TI  - Combination therapy with glucagon and a novel plasminogen activator inhibitor-1
      derived peptide enhances protection against impaired cerebrovasodilation during
      hypotension after traumatic brain injury through inhibition of ERK and JNK MAPK.
AB  - OBJECTIVE: Outcome of traumatic brain injury (TBI) is impaired by hypotension and
      glutamate, and TBI-associated release of endogenous tissue plasminogen activator
      (tPA) impairs cerebral autoregulation. Glucagon decreases central nervous system
      glutamate, lessens neuronal cell  injury, and improves neurological score in mice
      after TBI. Glucagon partially protects against impaired cerebrovasodilation
      during hypotension after TBI in piglets by upregulating cAMP which decreases
      release of tPA. Pial artery dilation during hypotension is due to release of cAMP
      dependent  dilator prostaglandins (PG), such as PGE2 and PGI2. TBI impairs PGE2
      and PGI2-mediated pial artery dilation, which contributes to disturbed cerebral
      autoregulation post-insult, by upregulating mitogen-activated protein kinase
      (MAPK). This study was designed to investigate relationships between  tPA,
      prostaglandins, and MAPK as a mechanism to improve the efficacy of glucagon
      mediated preservation of cerebrovasodilation during hypotension after TBI.
      METHODS: Lateral fluid percussion brain injury (FPI) was induced in piglets
      equipped with a closed cranial window. ERK and JNK  MAPK concentrations in
      cerebrospinal fluid were quantified by enzyme-linked immunosorbent assay.
      RESULTS: Cerebrospinal fluid JNK MAPK was increased by FPI, but blunted by
      glucagon and the novel plasminogen activator inhibitor-1-derived peptide (PAI
      1DP), Ac-RMAPEEIIMDRPFLYVVR-amide.  FPI modestly increased, while glucagon and
      PAI-1DP decreased ERK MAPK. PGE2, PGI2, N-methyl-D-aspartate, and hypotension
      induced pial artery dilation was blunted after FPI, partially protected by
      glucagon, and fully protected by glucagon+PAI-1DP, glucagon+JNK antagonist
      SP600125 or glucagon+ERK  inhibitor U 0126. DISCUSSION: Glucagon+PAI-1DP act in
      concert to protect against impairment of cerebrovasodilation during hypotension
      after TBI via inhibition of ERK and JNK MAPK.

PMID- 22642977
TI  - Host susceptibility is altered by light intensity after exposure to parasites.
AB  - Translating research advances to natural systems using experimental laboratory
      studies is often difficult because of the variability between the natural
      environment and experimental conditions. Because environmental conditions have a
      large effect on an organism's physiology, responses to stressors like nutrient
      limitation, temperature, oxygen deprivation, predation, and parasite/pathogen
      infection are likely to be context dependent. Therefore, it is essential to
      examine the impact the study environment has on the experimental outcome. Here,
      we explored the effect of light exposure on susceptibility to parasite infection.
      The Biomphalaria glabrata / Schistosoma mansoni study system is a well
      established model for studying schistosomiasis. It has been general practice to
      maintain the vector, B. glabrata, in dark conditions after exposure to miracidia
      of the human pathogen S. mansoni. We evaluated susceptibility of B. glabrata to
      S. mansoni under 3 different light conditions during the prepatent period, light
      (125 lx) on a 12-12 cycle, dim light (3 lx) on a 12-12 cycle, and no light (24 hr
      at 0 lx). We hypothesized that stress due to photoperiod disruption (24 hr of
      darkness) would result in compromised immune function and lead to higher
      susceptibility to infection. Prevalence of infected snails differed significantly
      between the light conditions, and higher susceptibility was observed in the full
      light and complete dark conditions compared with the low light conditions. The
      dim conditions are representative of current methods for evaluating
      susceptibility in this system. Our results indicate that light exposure during
      the prepatent period can affect infection outcomes, and environmental conditions
      must therefore be considered when assessing fitness and immune response due to
      interactions between host genotype and environment.

PMID- 22642978
TI  - Risk of placenta-mediated pregnancy complications or pregnancy-related VTE in VTE
      asymptomatic families of probands with VTE and heterozygosity for factor V Leiden
      or G20210 prothrombin mutation.
AB  - BACKGROUND: Few studies have evaluated the risk of pregnancy-related adverse
      events in asymptomatic relatives of probands for VTE and factor V Leiden or the
      G20210A variant. The antepartum management of this population ranges from
      antepartum anticoagulation therapy to clinical surveillance. OBJECTIVE: To
      evaluate the risk of placenta-mediated pregnancy complications and pregnancy
      related VTE in VTE-asymptomatic families of probands with VTE and who are
      heterozygous carriers of either factor V Leiden or PT-G20210A mutation. METHODS:
      One hundred and fifty-eight relatives, who had 415 pregnancies, were
      retrospectively evaluated. Odds ratios and 95% confidence intervals were
      calculated to compare pregnancy outcomes between women with and without
      thrombophilia. RESULTS: In the factor V Leiden group, 22 placenta-mediated
      pregnancy events of 152 pregnancies (14.4%) were reported, compared with 25
      adverse events of 172 pregnancies in the G20210A prothrombin group (14.5%) and 13
      adverse events of 91 pregnancies in the non-carrier group (14.2%). Carriers of
      factor V Leiden or G20210A prothrombin were not associated with a higher risk of
      pregnancy-adverse outcomes compared with non-carriers: OR 1.02 (95% CI, 0.40
      2.25) and 1.25 (95% CI, 0.48-3.24), respectively. Four episodes of pregnancy
      associated VTE of 415 pregnancies (0.96%) were recorded. Two episodes of VTE in
      the G20210A group, one in the factor V Leiden group, and one episode in the non
      carrier group were noted. CONCLUSIONS: In VTE-asymptomatic relatives of probands
      with VTE, the presence of factor V Leiden or the G20210A prothrombin mutation in
      heterozygosis should not lead to a decision to instigate antepartum prophylaxis.

PMID- 22642979
TI  - Muscle carbonic anhydrase III levels in normal and muscular dystrophia afflicted
      chickens.
AB  - BACKGROUND: The levels and immunohistochemical localization of muscle carbonic
      anhydrase III (CA-III) in healthy chickens and in muscular dystrophia affected
      (DA) chickens show that the muscles of diseased animal undergo a progressive
      increase of enzyme activity. METHODS: An enzyme-linked immunoassay was used to
      assess the CA-III levels in the muscles and other tissues from eight normal White
      Leghorn chickens and in two chickens with muscular dystrophy. Immunohistochemical
      localization of the enzyme in the muscles of these animals was also determined.
      RESULTS: The levels of CA-III in the tensor fasciae latae and the superficial
      pectoral muscles of the DA chickens were higher than the level in normal
      chickens. The concentrations of CA-III in erythrocytes and plasma from diseased
      chickens were approximately 15-fold and 1.4-fold higher than in the normal
      chickens, respectively. In the superficial pectoral and the tensor fasciae latae
      muscles of diseased chickens, the numbers of strongly stained and weakly stained
      fibers were greater than that in the normal chickens. CONCLUSION: The levels of
      CA-III in the superficial pectoral muscle, the tensor fasciae latae muscle,
      plasma and erythrocytes from the chickens with muscular dystrophy were higher
      than found in normal chickens.

PMID- 22642980
TI  - All that shines is not psychosis: a cautionary note on the assessment of
      psychotic symptoms in childhood and adolescence.

PMID- 22642982
TI  - Predictive toxicology modeling: protocols for exploring hERG classification and
      Tetrahymena pyriformis end point predictions.
AB  - The inclusion and accessibility of different methodologies to explore chemical
      data sets has been beneficial to the field of predictive modeling, specifically
      in the chemical sciences in the field of Quantitative Structure-Activity
      Relationship (QSAR) modeling. This study discusses using contemporary protocols
      and QSAR modeling methods to properly model two biomolecular systems that have
      historically not performed well using traditional and three-dimensional QSAR
      methodologies. Herein, we explore, analyze, and discuss the creation of a
      classification human Ether-a-go-go Related Gene (hERG) potassium channel model
      and a continuous Tetrahymena pyriformis (T. pyriformis) model using Support
      Vector Machine (SVM) and Support Vector Regression (SVR), respectively. The
      models are constructed with three types of molecular descriptors that capture the
      gross physicochemical features of the compounds: (i) 2D, 2 1/2D, and 3D physical
      features, (ii) VolSurf-like molecular interaction fields, and (iii) 4D
      Fingerprints. The best hERG SVM model achieved 89% accuracy and the three-best
      SVM models were able to screen a Pubchem data set with an accuracy of 97%. The
      best T. pyriformis model had an R(2) value of 0.924 for the training set and was
      able to predict the continuous end points for two test sets with R(2) values of
      0.832 and 0.620, respectively. The studies presented within demonstrate the
      predictive ability (classification and continuous end points) of QSAR models
      constructed from curated data sets, biologically relevant molecular descriptors,
      and Support Vector Machines and Support Vector Regression. The ability of these
      protocols and methodologies to accommodate large data sets (several thousands
      compounds) that are chemically diverse - and in the case of classification
      modeling unbalanced (one experimental outcome dominates the data set) - allows
      scientists to further explore a remarkable amount of biological and chemical
      information.

PMID- 22642981
TI  - Ethnic differences in risk factors and total risk of cardiovascular disease based
      on the Norwegian CONOR study.
AB  - BACKGROUND: Risk of cardiovascular disease varies between ethnic groups and the
      aim of this study was to investigate differences in cardiovascular risk factors,
      and total cardiovascular risk between ethnic groups in Norway. DESIGN: Cross
      sectional study using data from the Cohort of Norway (CONOR). METHODS: A sample
      of 62,145 participants, 40-65 years of age, originating from 11 geographical
      regions, were included in our study. Self-reported variables, blood samples and
      physical measurements were used to estimate age- and time-adjusted mean values of
      cardiovascular risk factors for different ethnic groups. The 10-year risks of
      cardiovascular mortality and cardiovascular events were calculated using the
      Framingham and NORRISK risk models. RESULTS: We observed differences between
      ethnic groups for cardiovascular risk factors and both Framingham and NORRISK
      risk scores. NORRISK showed significant differences by ethnicity in women only.
      Immigrants from the Indian subcontinent had the lowest high-density lipoprotein
      (HDL) levels, the highest levels of blood glucose, triglycerides, total
      cholesterol/HDL ratio, waist hip ratio and diabetes prevalence. Immigrants from
      the former Yugoslavia had the highest Framingham scores, high blood pressure,
      high total cholesterol/HDL ratio, overweight measures and smoking. Low
      cardiovascular risk was observed among East Asian immigrants. CONCLUSION: The
      previously reported excess cardiovascular risk among immigrants from the Indian
      subcontinent was supported in this study. We also showed that immigrants from the
      former Yugoslavian countries had a higher total 10-year risk of cardiovascular
      events than other ethnic groups. This study adds information about ethnic groups
      in Norway which needs to be addressed in further research and targeted prevention
      strategies.

PMID- 22642983
TI  - Effects of vision on head-putter coordination in golf.
AB  - Low-skill golfers coordinate the movements of their head and putter with an
      allocentric, isodirectional coupling, which is opposite to the allocentric,
      antidirectional coordination pattern used by experts (Lee, Ishikura, Kegel,
      Gonzalez, & Passmore, 2008). The present study investigated the effects of four
      vision conditions (full vision, no vision, target focus, and ball focus) on head
      putter coupling in low-skill golfers. Performance in the absence of vision
      resulted in a level of high isodirectional coupling that was similar to the full
      vision condition. However, when instructed to focus on the target during the
      putt, or focus on the ball through a restricted viewing angle, low-skill golfers
      significantly decoupled the head--putter coordination pattern. However, outcome
      measures demonstrated that target focus resulted in poorer performance compared
      with the other visual conditions, thereby providing overall support for use of a
      ball focus strategy to enhance coordination and outcome performance. Focus of
      attention and reduced visual tracking were hypothesized as potential reasons for
      the decoupling.

PMID- 22642984
TI  - Photodynamic therapy: shining new light on limiting the collateral damage of
      ablation?

PMID- 22642985
TI  - Bone and mucosal dosimetry in skin radiation therapy: a Monte Carlo study using
      kilovoltage photon and megavoltage electron beams.
AB  - This study examines variations of bone and mucosal doses with variable soft
      tissue and bone thicknesses, mimicking the oral or nasal cavity in skin radiation
      therapy. Monte Carlo simulations (EGSnrc-based codes) using the clinical
      kilovoltage (kVp) photon and megavoltage (MeV) electron beams, and the pencil
      beam algorithm (Pinnacle(3) treatment planning system) using the MeV electron
      beams were performed in dose calculations. Phase-space files for the 105 and 220
      kVp beams (Gulmay D3225 x-ray machine), and the 4 and 6 MeV electron beams
      (Varian 21 EX linear accelerator) with a field size of 5 cm diameter were
      generated using the BEAMnrc code, and verified using measurements. Inhomogeneous
      phantoms containing uniform water, bone and air layers were irradiated by the kVp
      photon and MeV electron beams. Relative depth, bone and mucosal doses were
      calculated for the uniform water and bone layers which were varied in thickness
      in the ranges of 0.5-2 cm and 0.2-1 cm. A uniform water layer of bolus with
      thickness equal to the depth of maximum dose (d(max)) of the electron beams (0.7
      cm for 4 MeV and 1.5 cm for 6 MeV) was added on top of the phantom to ensure that
      the maximum dose was at the phantom surface. From our Monte Carlo results, the 4
      and 6 MeV electron beams were found to produce insignificant bone and mucosal
      dose (<1%), when the uniform water layer at the phantom surface was thicker than
      1.5 cm. When considering the 0.5 cm thin uniform water and bone layers, the 4 MeV
      electron beam deposited less bone and mucosal dose than the 6 MeV beam. Moreover,
      it was found that the 105 kVp beam produced more than twice the dose to bone than
      the 220 kVp beam when the uniform water thickness at the phantom surface was
      small (0.5 cm). However, the difference in bone dose enhancement between the 105
      and 220 kVp beams became smaller when the thicknesses of the uniform water and
      bone layers in the phantom increased. Dose in the second bone layer interfacing
      with air was found to be higher for the 220 kVp beam than that of the 105 kVp
      beam, when the bone thickness was 1 cm. In this study, dose deviations of bone
      and mucosal layers of 18% and 17% were found between our results from Monte Carlo
      simulation and the pencil-beam algorithm, which overestimated the doses. Relative
      depth, bone and mucosal doses were studied by varying the beam nature, beam
      energy and thicknesses of the bone and uniform water using an inhomogeneous
      phantom to model the oral or nasal cavity. While the dose distribution in the
      pharynx region is unavailable due to the lack of a commercial treatment planning
      system commissioned for kVp beam planning in skin radiation therapy, our study
      provided an essential insight into the radiation staff to justify and estimate
      bone and mucosal dose.

PMID- 22642986
TI  - Comparing variational Bayes with Markov chain Monte Carlo for Bayesian
      computation in neuroimaging.
AB  - In this article, we consider methods for Bayesian computation within the context
      of brain imaging studies. In such studies, the complexity of the resulting data
      often necessitates the use of sophisticated statistical models; however, the
      large size of these data can pose significant challenges for model fitting. We
      focus specifically on the neuroelectromagnetic inverse problem in
      electroencephalography, which involves estimating the neural activity within the
      brain from electrode-level data measured across the scalp. The relationship
      between the observed scalp-level data and the unobserved neural activity can be
      represented through an underdetermined dynamic linear model, and we discuss
      Bayesian computation for such models, where parameters represent the unknown
      neural sources of interest. We review the inverse problem and discuss variational
      approximations for fitting hierarchical models in this context. While variational
      methods have been widely adopted for model fitting in neuroimaging, they have
      received very little attention in the statistical literature, where Markov chain
      Monte Carlo is often used. We derive variational approximations for fitting two
      models: a simple distributed source model and a more complex spatiotemporal
      mixture model. We compare the approximations to Markov chain Monte Carlo using
      both synthetic data as well as through the analysis of a real
      electroencephalography dataset examining the evoked response related to face
      perception. The computational advantages of the variational method are
      demonstrated and the accuracy associated with the resulting approximations are
      clarified. 

PMID- 22642987
TI  - A protein phosphatase 2A catalytic subunit modulates blue light-induced
      chloroplast avoidance movements through regulating actin cytoskeleton in
      Arabidopsis.
AB  - Chloroplast avoidance movements mediated by phototropin 2 (phot2) are one of most
      important physiological events in the response to high-fluence blue light (BL),
      which reduces damage to the photosynthetic machinery under excess light. Protein
      phosphatase 2A-2 (PP2A-2) is an isoform of the catalytic subunit of PP2A, which
      regulates a number of developmental processes. To investigate whether PP2A-2 was
      involved in high-fluence BL-induced chloroplast avoidance movements, we first
      analyzed chloroplast migration in the leaves of the pp2a-2 mutant in response to
      BL. The data showed that PP2A-2 might act as a positive regulator in phot2
      mediated chloroplast avoidance movements, but not in phot1-mediated chloroplast
      accumulation movements. Then, the effect of okadaic acid (OA) and cantharidin
      (selective PP2A inhibitors) on high-fluence BL response was further investigated
      in Arabidopsis thaliana mesophyll cells. Within a certain concentration range,
      exogenously applied OA or cantharidin inhibited the high-fluence BL-induced
      chloroplast movements in a concentration-dependent manner. Actin depolymerizing
      factor (ADF)/cofilin phosphorylation assays demonstrated that PP2A-2 can
      activate/dephosphorylate ADF/cofilin, an actin-binding protein, in Arabidopsis
      mesophyll cells. Consistent with this observation, the experiments showed that OA
      could inhibit ADF1 binding to the actin and suppress the reorganization of the
      actin cytoskeleton after high-fluence BL irradiation. The adf1 and adf3 mutants
      also exhibited reduced high-fluence BL-induced chloroplast avoidance movements.
      In conclusion, we identified that PP2A-2 regulated the activation of ADF/cofilin,
      which, in turn, regulated actin cytoskeleton remodeling and was involved in phot2
      mediated chloroplast avoidance movements.

PMID- 22642988
TI  - Oil accumulation is controlled by carbon precursor supply for fatty acid
      synthesis in Chlamydomonas reinhardtii.
AB  - Microalgal oils have attracted much interest as potential feedstocks for
      renewable fuels, yet our understanding of the regulatory mechanisms controlling
      oil biosynthesis and storage in microalgae is rather limited. Using Chlamydomonas
      reinhardtii as a model system, we show here that starch, rather than oil, is the
      dominant storage sink for reduced carbon under a wide variety of conditions. In
      short-term treatments, significant amounts of oil were found to be accumulated
      concomitantly with starch only under conditions of N starvation, as expected, or
      in cells cultured with high acetate in otherwise standard growth medium. Time
      course analysis revealed that oil accumulation under N starvation lags behind
      that of starch and rapid oil synthesis occurs only when carbon supply exceeds the
      capacity of starch synthesis. In the starchless mutant BAFJ5, blocking starch
      synthesis results in significant increases in the extent and rate of oil
      accumulation. In the parental strain, but not the starchless mutant, oil
      accumulation under N starvation was strictly dependent on the available external
      acetate supply and the amount of oil increased steadily as the acetate
      concentration increased to the levels several-fold higher than that of the
      standard growth medium. Additionally, oil accumulation under N starvation is
      saturated at low light intensities and appears to be largely independent of de
      novo protein synthesis. Collectively, our results suggest that carbon
      availability is a key metabolic factor controlling oil biosynthesis and carbon
      partitioning between starch and oil in Chlamydomonas.

PMID- 22642989
TI  - Functional identification of OsHk6 as a homotypic cytokinin receptor in rice with
      preferential affinity for iP.
AB  - Cytokinins are involved in key developmental processes in rice (Oryza sativa),
      including the regulation of cell proliferation and grain yield. However, the in
      vivo action of histidine kinases (OsHks), putative cytokinin receptors, in rice
      cytokinin signaling remains elusive. This study examined the function and
      characteristics of OsHk3, 4 and 6 in rice. OsHk6 was highly sensitive to
      isopentenyladenine (iP) and was capable of restoring cytokinin-dependent ARR6
      reporter expression in the ahk2 ahk3 Arabidopsis mutant upon treatment with 1 nM
      iP. OsHk4 recognized trans-zeatin (tZ) and iP, while OsHk3 scarcely induced
      cytokinin signaling activity. OsHk4 and OsHk6 mediated the canonical two
      component signaling cascade of Arabidopsis to induce phosphorylation of ARR2.
      OsHk4 and OsHk6 were highly expressed in spikelets, suggesting that tZ and iP
      might play key roles in grain development. OsHk6 formed a self-interacting
      homomer in rice protoplasts, although the trans-phosphorylation activity between
      subunits was much lower than the intra-molecular trans-phosphorylation activity.
      This indicates that the action mechanism of OsHks is evolutionarily diverged from
      bacterial histidine kinases. Ectopic expression of OsHk6 in rice calli promoted
      green pigmentation and subsequent shoot induction, further supporting an OsHk6 in
      planta function as a cytokinin receptor. From the results of this study, OsHks
      are homomeric cytokinin receptors with distinctive cytokinin preferences in rice.

PMID- 22642990
TI  - [Male infertility today].

PMID- 22642991
TI  - [Mutations in genes involved in splicing in human malignancies].

PMID- 22642992
TI  - [The western medicine is fan of Tai Chi].

PMID- 22642993
TI  - [JAK/STAT: from inflammation to memory].

PMID- 22642994
TI  - [Ars2, an essential player in neural stem cell identity].

PMID- 22642995
TI  - [Malaria: is there a role for the iron-hepcidin axis?].

PMID- 22642996
TI  - [DCC, come back of a suppressor gene in colorectal cancer].

PMID- 22642997
TI  - [Srf: a key factor controlling skeletal muscle hypertrophy by enhancing the
      recruitment of muscle stem cells].

PMID- 22642998
TI  - [How to do more with less within the nervous system: engrailed chooses the
      mitochondria].

PMID- 22642999
TI  - [NKT cells in the liver environment interact with Wnt/beta-catenin and promote
      the emergence of liver carcinoma].

PMID- 22643000
TI  - [New painkillers inhibiting the physiological breakdown of endogenous opioids].

PMID- 22643001
TI  - [Cross-fire over the nucleosome: molecular basis of post-meiotic male haploid
      genome compaction].
AB  - In mammals, the post-meiotic phases of spermatogenesis direct a drastic
      compaction of the genome characterized by the replacement of the majority of
      histones by small basic non-histone proteins, transition proteins followed by
      protamines. Although the mechanisms controlling this process are poorly
      understood, available data suggest that the nucleosome, which represents the
      universal unit of genome organization in eukaryotes, is the target of specific
      events cooperating to globally transform DNA organization at a genomic scale.
      Indeed, after meiosis, nearly all nucleosomes associated with the male genome
      undergo successive modifications increasing their instability, finally leading to
      their dissociation and re-organization. The characterization of the underlying
      mechanisms is a real challenge and appears as essential for the understanding of
      male gametogenesis and associated pathologies.

PMID- 22643002
TI  - [Non-coding small RNAs and spermatogenesis].
AB  - The continuous production of spermatozoa is a tightly regulated biological
      process, both at the transcriptional and post-transcriptional levels. Recently,
      different classes of small non-coding RNAs have emerged as important regulators
      of spermatogenesis. Available molecular and genetic data, although still
      fragmented, underscore their crucial role in regulating the fine tuning of gene
      expression required for testicular function. Here, we review the latest advances
      accomplished in this domain, spanning from the biogenesis of these small non
      coding RNAs to their roles in male reproductive function.

PMID- 22643003
TI  - [Genetics of male infertility: the new players].
AB  - Approximately 10-15% of couples experience infertility and male factors
      contribute to half of these cases. It was usually thought that infertility cannot
      be transmitted, but accumulating evidence indicates that many cases are indeed
      caused by genetic defects, some inherited. The use of single nucleotide
      polymorphisms (SNP) arrays allowing to genotype the totality of the genome
      recently led to identify several genes which, when mutated, generate specific
      infertility phenotypes. With the tremendous progresses in high throughput
      sequencing techniques, we can expect many more new genes involved in fertility to
      be identified in the next years. For the patients concerned, these findings mean
      the possibility of an accurate diagnosis and improved prognosis. Furthermore,
      these data will lead to a better understanding of the molecular mechanisms
      underlying spermatogenesis and thus should contribute to identify and offer new
      therapeutic strategies for the treatment of infertility.

PMID- 22643004
TI  - [Morphological defects of sperm flagellum implicated in human male infertility].
AB  - The assembly of sperm flagella involves specific components and processes that
      are still poorly defined. Several morphological defects of the different
      structures that compose the axoneme have been described and associated to human
      male infertility. These morphological defects can be classified in 15 main
      categories. Most of them have been associated to consanguinity and/or familial
      cases, suggesting their genetic origin. However, so far only few genes have been
      causally involved.

PMID- 22643006
TI  - [Post-testicular protection of male gametes from oxidative damage. The role of
      the epididymis].
AB  - Spermatozoa leave the testis in an immature functional state and are devoid of
      self defense mechanisms. They will become motile and ready to fertilize only
      after their descent and their progressive maturation within the epididymal
      tubule. The epididymis also ensures the survival and the protection of male
      gametes while they go through the epididymis and during their storage in between
      two ejaculations. Amongst common stresses that concern spermatozoa, oxidative
      stress occupies a peculiar and dual position. While the events of epididymal
      sperm maturation necessitate a given level of oxidation, spermatozoa are
      particularly sensitive to oxidative damage. A fine balance between beneficial
      oxidation versus detrimental oxidative damage has to be maintained in the
      epididymal environment. Antioxidant enzymes of the glutathione peroxidase family
      play a key role in controling such a situation in the epididymis.

PMID- 22643005
TI  - [Do phospholipases, key enzymes in sperm physiology, represent therapeutic
      challenges?].
AB  - The spermatozoon is one of the most differentiated cells in mammals and its
      production requires an extremely complex machinery. Subtle but critical molecular
      changes take place during capacitation, which comprises the last series of
      maturation steps that naturally occur between the cauda epididymidis where
      spermatozoa are stored and their ultimate destination inside the oocyte.
      Phospholipases, by hydrolyzing various phospholipids, have been found to be
      critical in sperm processes such as 1) the control of flagellum beats, 2)
      capacitation - the molecular transformations preparing the sperm for
      fertilization, 3) acrosome reaction and 4) oocyte activation by eliciting calcium
      oscillations. The emerging important role of phospholipases is also emphasized by
      the fact that alterations of sperm lipids can lead to infertility. Phospholipases
      may represent valuable targets to develop anti- and pro-fertility drugs. Results
      obtained in mice are encouraging, since treatment of sperm with recombinant
      sPLA(2) of group X, known to be involved in capacitation, improves fertilization
      in vitro, while co-injection of PLCzeta RNA with infertile sperm restores oocyte
      activation.

PMID- 22643007
TI  - [The process of X inactivation in the mouse].
AB  - X chromosome inactivation (XCI) is an excellent model for studying how epigenetic
      marks are initiated during early embryogenesis. XCI is an essential process that
      takes place in females, leading to dosage compensation between males and females.
      In mouse, it occurs in two waves: the first one is paternally imprinted, during
      the preimplantation period and the second one occurs in a random fashion. We
      provide here an update of the main molecular steps and hypothesis underlining
      this complex process.

PMID- 22643008
TI  - [The 18(th) century between Ecorches and plastinated bodies, two female waxwork
      modelists: Anna Morandi and Marie-Marguerite Biheron].

PMID- 22643009
TI  - [Search for natural substances with therapeutic activity: Pierre Potier (1934
      2006)].

PMID- 22643010
TI  - [From emergent viruses to resistant bacteria, a sanitary crisis and its effects].

PMID- 22643011
TI  - [Are expression signatures worthless?].

PMID- 22643012
TI  - [IgH locus suicide recombination, or when B cells surrender!].

PMID- 22643013
TI  - A novel diagnostic sign of hip fracture mechanism in ground level falls: two case
      reports and review of the literature.
AB  - INTRODUCTION: Most elderly hip fractures are the result of a ground level fall.
      Defining high risk falls and fracture mechanisms are important to develop
      successful hip fracture prevention programs. This case series presents a
      previously unreported diagnostic sign and for the first time documents a hip
      fracture mechanism for a knee impact injury from a ground level fall in two
      elderly patients. CASE PRESENTATION: Case 1 was a 65-year-old Caucasian woman who
      fell forward with initial contact to her left knee, sustaining an impacted
      femoral neck fracture of her ipsilateral left hip. Case 2 was a 92-year-old
      Caucasian woman who fell bending forward, impacting her left knee and sustaining
      a comminuted intertrochanteric fracture of her ipsilateral left hip. The
      fractures occurred as a result of unprotected ground level falls in a forward
      direction with initial impact to the knee. The knee contusions were located near
      Gerdy's tubercle and appear characteristic of a direct impact injury. CONCLUSION:
      The physical finding of a small localized site of impact and/or contusion in the
      anterior aspect of the knee in both of these patients with radiographic evidence
      of an ipsilateral hip fracture would strongly suggest that a knee impact injury
      can transmit enough energy to the proximal femur by axial loading to result in
      the hip fracture. The physical finding described is a reliable indicator of this
      hip fracture mechanism.

PMID- 22643014
TI  - Mid-way and post-intervention effects on potential determinants of physical
      activity and sedentary behavior, results of the HEIA study - a multi-component
      school-based randomized trial.
AB  - BACKGROUND: There is limited knowledge as to whether obesity prevention
      interventions are able to produce change in the determinants hypothesized to
      precede change in energy balance-related behaviors in young people. The aim of
      this study was to evaluate the effect of a multi-component intervention on a wide
      range of theoretically informed determinants of physical activity (PA) and
      sedentary behavior (SB). Moderation effects of gender, weight status and parental
      education level and whether the perceived intervention dose received influenced
      the effects were also explored. METHODS: The HEIA study was a 20-month school
      based, randomized controlled trial to promote healthy weight development. In
      total, 1418 11-year-olds participated at baseline and post-intervention
      assessment. Enjoyment, self-efficacy, perceived social support from parents,
      teachers and friends related to PA, perceived parental regulation of TV-viewing
      and computer/game-use and perceived social inclusion at schools were examined by
      covariance analyses to assess overall effects and moderation by gender, weight
      status and parental education, mid-way and post-intervention. Covariance analyses
      were also used to examine the role of intervention dose received on change in the
      determinants. RESULTS: At mid-way enjoyment (p = .03), perceived social support
      from teachers (p = .003) and self-efficacy (p = .05) were higher in the
      intervention group. Weight status moderated the effect on self-efficacy, with a
      positive effect observed among the normal weight only. At post-intervention
      results were sustained for social support from teachers (p = .001), while a
      negative effect was found for self-efficacy (p = .02). Weight status moderated
      the effect on enjoyment, with reduced enjoyment observed among the overweight.
      Moderation effects for parental education level were detected for perceived
      social support from parents and teachers. Finally, positive effects on several
      determinants were observed among those receiving a high as opposed to a low
      intervention dose. CONCLUSION: The intervention affected both psychological and
      social-environmental determinants. Results indicate that social support from
      teachers might be a potential mediator of PA change, and that overweight
      adolescents might be in need of specially targeted interventions to avoid
      reducing their enjoyment of PA. Further studies should continue to assess how
      intervention effectiveness is influenced by the participants' self-reported dose
      of intervention received.

PMID- 22643015
TI  - Endocrine-mediated effects of two benzene related compounds, 1-chloro-4
      (chloromethyl)benzene and 1,3-diethyl benzene, based on subacute oral toxicity
      studies using rats.
AB  - The purpose of this study was to investigate the endocrine-mediated effects of
      the benzene-related compounds with reference to Organization for Economic Co
      operation and Development (OECD) Test Guideline No. 407. Rats were orally gavaged
      with 0, 10, 50, and 250 mg/kg/day of 1-chloro-4-(chloromethyl)benzene, and 0, 25,
      150, and 1000 mg/kg/day of 1,3-diethyl benzene for at least 28 days, beginning at
      8 weeks of age. Thyroid dysfunction was observed in rats given the 1,3-diethyl
      benzene. Serum T4 values increased in all groups of male rats and in the 1000
      mg/kg group of female rats, and TSH values also increased in the 1000 mg/kg
      groups of both sexes after 28 days' administration. Decreased T3 values were
      observed in the 1000 mg/kg group of female rats after 28 days' administration,
      and hormone values increased in the 1000 mg/kg groups of both sexes after the 14
      day recovery period. In addition, thyroid weight increased in the 1000 mg/kg
      groups and thyroid follicular cell hyperplasia was detected in one male rat from
      the 1000 mg/kg group after 28 days' administration. Endocrine-mediated effects,
      including thyroid dysfunction were not observed in any groups of rats treated
      with 1-chloro-4-(chloromethyl)benzene. Our results indicated that endocrine
      mediated effects such as thyroid dysfunction were associated with some benzene
      related compounds.

PMID- 22643016
TI  - Detection of previously undiagnosed cases of COPD in a high-risk population
      identified in general practice.
AB  - BACKGROUND AND AIM: Under-diagnosis of COPD is a widespread problem. This study
      aimed to identify previously undiagnosed cases of COPD in a high-risk population
      identified through general practice. METHODS: Participating GPs (n = 241)
      recruited subjects with no previous diagnosis of lung disease, >35 yrs, and at
      least one respiratory symptom. Age, smoking status, pack-years, BMI, dyspnoea
      score (MRC), and pre-bronchodilator spirometry data was obtained. Subjects with
      airway obstruction (FEV(1)/FVC <= 0.7) at initial spirometry were tested for
      reversibility, according to Danish COPD guidelines, with bronchodilator and, if
      necessary, corticosteroids in order to confirm a diagnosis of COPD. RESULTS: A
      total of 4.049 (49% females) subjects were included; mean age 58 yrs, BMI 27, and
      32 pack-years. The COPD prevalence was 21.7%; 8.3% in subjects younger than 48
      years. Most patients were classified in GOLD stages I and II (36% and 50%,
      respectively). The number needed to screen (NNS) for a new diagnosis of COPD was
      4.6. COPD diagnosis was related to gender, age, BMI (p < 0.001), pack-years, and
      cough (p < 0.001), wheezing (p < 0.001) and sputum production (p = 0.002). A
      threshold of 10% pre-test risk of COPD would have reduced the number of
      spirometry tests by 35% although 90% of the patients with COPD would still have
      been identified (NNS 3.9). CONCLUSIONS: Of the at-risk subjects studied, 22% were
      diagnosed with COPD. A case-finding strategy providing questionnaire assessment
      and diagnostic spirometry to high-risk subjects in primary care, and therefore,
      identifies a large proportion of undiagnosed COPD patients, especially in the
      early stages of the disease.

PMID- 22643017
TI  - Can a young muscle's stem cell secretome prolong our lives?
AB  - Ageing is a biological certainty for all living organisms, and is due to the loss
      of tissue homeostasis and regenerative capacity (except for newts) in which
      somatic stem cells are thought to play an important role. Many ageing-associated
      dysfunctions in stem cells have been described, but it remains ambiguous whether
      these are merely an outcome of ageing or are causal. Parabiotic animal studies
      suggest there are factors in the systemic environment that can influence the
      regenerative capacity of tissues. These factors can be altered by ageing, but it
      is not clear where these age-dependent factors are derived. A recent provocative
      study on muscle stem cells, in a mouse model of human progeria, proposes a
      mechanism that might provide answers to these fundamental ageing questions.

PMID- 22643018
TI  - Undergraduate teaching in the outpatient clinic: Can we do better?

PMID- 22643019
TI  - Mixed messages in learning communication skills? Students comparing role model
      behaviour in clerkships with formal training.
AB  - BACKGROUND: Medical students learn professional communication through formal
      training and in clinical practice. Physicians working in clinical practice have a
      powerful influence on student learning. However, they may demonstrate
      communication behaviours not aligning with recommendations in training programs.
      AIMS: This study aims to identify more precisely what differences students
      perceive between role model communication behaviour during clerkships and formal
      training. METHOD: In a cross-sectional study, data were collected about
      physicians' communication performance as perceived by students. Students filled
      out a questionnaire in four different clerkships in their fourth and fifth year.
      RESULTS: Just over half of the students reported communication similar to formal
      training. This was especially true for students in the later clerkships
      (paediatrics and primary care). Good examples were seen in providing information
      corresponding to patients' needs and in shared decision making, although students
      often noted that in fact the doctor made the decision. Bad examples were observed
      in exploring cognitions and emotions, and in providing information meeting
      patient's pace. CONCLUSIONS: Further study is needed on actual physician
      behaviour in clinical practice. From our results, we conclude that students need
      help in reflecting on and learning from the gap in communication patterns they
      observe in training versus clinical practice.

PMID- 22643020
TI  - Dissatisfaction with residency: a discrepancy between preferences and
      expectations?
AB  - BACKGROUND: Medical residents play two roles that enter into conflict during
      their educational period: trainees and workers. This dual role can lead to
      dissatisfaction among residents that can affect both the quality of the services
      they provide to citizens and the proper functioning of the health services model
      itself. AIM: To analyse discrepancies between the preferences and expectations of
      first-year medical residents and whether these differences affect satisfaction
      with the residency. METHOD: A questionnaire was administered on-line to the
      entire population of first-year medical residents of the Autonomous Community of
      Andalusia (Spain) in 2008. We performed a means contrast test between the
      indicator discrepancy (difference between preferences and expectations during the
      residency as a training or a working period), overall satisfaction with the
      residency and their relationship to other expectations of medical residents.
      RESULTS: Respondents showing greater discrepancy have a more negative opinion
      about the residency. CONCLUSION: There is a gap between what residents prefer and
      what they expect from the residency, giving rise to dissatisfaction. This gap
      must be bridged to improve the quality of training received by these new
      physicians, their satisfaction and hence the delivery of health services to
      citizens.

PMID- 22643021
TI  - Applying a quality assurance system model to curriculum transformation:
      transferable lessons learned.
AB  - As curricula are transformed throughout the world in response to the need for
      modern medical education, much attention is given to curriculum content and
      associated teaching, learning and assessment methodologies. However, an important
      component of any curriculum is its organisational management, how it is all held
      together, the way the process is conducted and what mechanisms are applied to
      ensure quality.   In 2008, the Faculty of Medicine at Damascus University
      embarked on a journey of curriculum transformation. The transformation process
      was specifically and initially based on a quality assurance model. This entailed
      a concept for realising curriculum transformation; a framework for organisational
      management, which ensures that the necessary enabling conditions are met and
      issues of conflicts in roles and responsibilities are resolved; a plan for
      securing resources and creating the necessary governance structures needed to
      carry the transformation process forward; and a systematic analysis of risks
      facing the effective realisation of the transformation process and the
      corresponding mitigation measures to alleviate their impacts.   Although a full
      evaluation of such an activity produces reliable results only after a period of
      time, this article demonstrates the principles and structures applied to the
      initial process based on some of the early lessons learned. We perceive that the
      lessons learned from this activity are capable of being translated to other
      Universities, in other similar developing countries; our hope is that others can
      learn from our experiences.

PMID- 22643022
TI  - Becoming a peer reviewer to medical education journals.
AB  - BACKGROUND: Peer reviewing for medical education journals is an art, a privilege,
      a responsibility and a service to the profession. Writing a review report
      requires skills and commitment and takes time. Novice reviewers may be interested
      in participating in this service, but they might lack sufficient knowledge of
      their role as peer reviewers and the skills needed to conduct a comprehensive and
      fair review. AIMS: The aims of this article are to help novice reviewers in their
      preparation of manuscript review reports and improve their confidence and skills
      in their role as reviewers. METHODS: We reviewed the literature in this area and
      applied lessons learned from our experience as peer reviewers. In addition, one
      of the authors has presented several training workshops for faculty reviewers.
      RESULTS: Incorporating all the methods described, we have developed a series of
      simple strategies that medical educators can utilise to perform high-quality
      reviews of manuscripts. CONCLUSIONS: Though the development of skills in
      reviewing medical education papers is the outcome of continuous practice and
      experience; the strategies described in this article will be of value to those
      starting their professional contribution as reviewers and enhance their skills in
      this area.

PMID- 22643023
TI  - Prevalence of intimate partner violence in patients presenting with traumatic
      injuries to a Guyanese emergency department.
AB  - BACKGROUND: Intimate partner violence (IPV) occurs throughout the world, and has
      both short- term and long- term negative health effects. Little is know about the
      prevalence of IPV in patients presenting to Emergency Departments (EDs) in the
      developing world. This information is needed to help delineate the scope of the
      problem and shape effective interventions to combat IPV. The purpose of this
      study was to determine the prevalence of intimate partner violence in adult
      patients with acute traumatic injuries presenting to an ED in Georgetown, Guyana.
      METHODS: Retrospective descriptive analysis of a prospectively collected ED
      quality assurance database. Patients 18 years or older who presented with a
      traumatic injury and answered the question "Was the injury inflicted by a
      domestic partner?" were included in the analysis. RESULTS: Overall, 38 of 475
      (8%) patients admitted to having injuries inflicted by a domestic partner. Thirty
      one (81.6%) patients disclosing IPV were female and 7 (18.4%) were male. The
      self- reported prevalence of IPV in females presenting with traumatic injuries
      was 16% compared to 2% for males (RR 6.4; 95% CI 2.9-14.3). IPV was the cause of
      31 of the 67 (46.3%) women presenting with assaults. CONCLUSIONS: IPV is thought
      to be a serious problem in Guyana, and this study confirms a high prevalence
      (16%) of IPV in women presenting with traumatic injuries to the Georgetown Public
      Hospital Corporation ED. This is likely a significant underestimate of the true
      prevalence.

PMID- 22643025
TI  - Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived
      oral cell lines reveals loss of spatial regulation of CD44 and p75 NTR in
      malignancy.
AB  - Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The
      role of cancer stem cells in tumour initiation is widely accepted, yet the
      potential existence of pre-cancerous stem cells in dysplastic tissue has received
      little attention. Cell lines from oral diseases ranging in severity from
      dysplasia to malignancy provide opportunity to investigate the involvement of
      stem cells in malignant progression from dysplasia. Stem cells are functionally
      defined by their ability to generate hierarchical tissue structures in consortium
      with spatial regulation. Organotypic cultures readily display tissue hierarchy in
      vitro; hence, in this study, we compared hierarchical expression of stem cell
      associated markers in dermis-based organotypic cultures of oral epithelial cells
      from normal tissue (OKF6-TERT2), mild dysplasia (DOK), severe dysplasia (POE-9n)
      and OSCC (PE/CA P J15). Expression of CD44, p75(NTR), CD24 and ALDH was studied
      in monolayers by flow cytometry and in organotypic cultures by
      immunohistochemistry. Spatial regulation of CD44 and p75(NTR) was evident for
      organotypic cultures of normal (OKF6-TERT2) and dysplasia (DOK and POE-9n) but
      was lacking for OSCC (PE/CA PJ15)-derived cells. Spatial regulation of CD24 was
      not evident. All monolayer cultures exhibited CD44, p75(NTR), CD24 antigens and
      ALDH activity (ALDEFLUOR((r)) assay), with a trend towards loss of population
      heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and
      decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and
      NANOG did not. We conclude that dermis-based organotypic cultures give
      opportunity to investigate the mechanisms that underlie loss of spatial
      regulation of stem cell markers seen with OSCC-derived cells.

PMID- 22643026
TI  - Functional region prediction with a set of appropriate homologous sequences--an
      index for sequence selection by integrating structure and sequence information
      with spatial statistics.
AB  - BACKGROUND: The detection of conserved residue clusters on a protein structure is
      one of the effective strategies for the prediction of functional protein regions.
      Various methods, such as Evolutionary Trace, have been developed based on this
      strategy. In such approaches, the conserved residues are identified through
      comparisons of homologous amino acid sequences. Therefore, the selection of
      homologous sequences is a critical step. It is empirically known that a certain
      degree of sequence divergence in the set of homologous sequences is required for
      the identification of conserved residues. However, the development of a method to
      select homologous sequences appropriate for the identification of conserved
      residues has not been sufficiently addressed. An objective and general method to
      select appropriate homologous sequences is desired for the efficient prediction
      of functional regions. RESULTS: We have developed a novel index to select the
      sequences appropriate for the identification of conserved residues, and
      implemented the index within our method to predict the functional regions of a
      protein. The implementation of the index improved the performance of the
      functional region prediction. The index represents the degree of conserved
      residue clustering on the tertiary structure of the protein. For this purpose,
      the structure and sequence information were integrated within the index by the
      application of spatial statistics. Spatial statistics is a field of statistics in
      which not only the attributes but also the geometrical coordinates of the data
      are considered simultaneously. Higher degrees of clustering generate larger index
      scores. We adopted the set of homologous sequences with the highest index score,
      under the assumption that the best prediction accuracy is obtained when the
      degree of clustering is the maximum. The set of sequences selected by the index
      led to higher functional region prediction performance than the sets of sequences
      selected by other sequence-based methods. CONCLUSIONS: Appropriate homologous
      sequences are selected automatically and objectively by the index. Such sequence
      selection improved the performance of functional region prediction. As far as we
      know, this is the first approach in which spatial statistics have been applied to
      protein analyses. Such integration of structure and sequence information would be
      useful for other bioinformatics problems.

PMID- 22643027
TI  - Toxicity assessment of extracts from infusion sets in cEND brain endothelial
      cells.
AB  - In vitro safety assessment of disposable medical devices, including infusion
      sets, is usually performed using L-929 mouse keratinocytes. However, cells of
      different origin (endothelial, lymphoid and myeloid cells) are also exposed to
      infusion sets' extractables during their clinical use. We studied whether the
      cEND mouse brain endothelial cells can be suitable for in vitro safety assessment
      of infusion sets. We analyzed infusion sets from different manufacturers that
      varied in design and storage time. cEND cells were incubated with extracts of
      individual parts of the infusion sets (tube, cup, latex), and relative toxicities
      were analyzed using MTT test, DCFH-DA-based analysis of reactive oxygen species
      formation, apoptosis and cell cycle analyses. We identified a pattern of
      yellowing of the infusion sets upon storage and revealed that it originated from
      the latex part. Extracts of the individual parts of the infusion sets, primarily
      of the latex, were toxic to the cEND cells leading to induction of apoptosis and
      cell death. We conclude that infusion sets release extractables that can be toxic
      to the endothelial cells of the patients that receive infusion. We suggest to use
      cEND cells for in vitro safety assessment of infusion sets and other medical
      devices that release extractables to the bloodstream.

PMID- 22643028
TI  - Handwriting: three-dimensional kinetic synergies in circle drawing movements.
AB  - The purpose of this study was to investigate central nervous system (CNS)
      strategies for controlling multifinger forces during a circle-drawing task.
      Subjects drew 30 concentric, discontinuous clockwise and counter clockwise
      circles, at self and experimenter-set paces. The three-dimensional trajectory of
      the pen's center of mass and the three-dimensional forces and moments of force at
      each contact between the hand and the pen were recorded. Uncontrolled Manifold
      Analysis was used to quantify the synergies between pen-hand contact forces in
      radial, tangential and vertical directions. Results showed that synergies in the
      radial and tangential components were significantly stronger than in the vertical
      component. Synergies in the clockwise direction were significantly stronger than
      the counterclockwise direction in the radial and vertical components. Pace was
      found to be insignificant under any condition.

PMID- 22643029
TI  - Mobile psychiatry: towards improving the care for bipolar disorder.
AB  - BACKGROUND: Mental health has long been a neglected problem in global healthcare.
      The social and economic impacts of conditions affecting the mind are still
      underestimated. However, in recent years it is becoming more apparent that mental
      disorders are a growing global concern and there is a necessity of developing
      novel services and researching effective means of providing interventions to
      sufferers. Such novel services could include technology-based solutions already
      used in other healthcare applications but are yet to make their way into standard
      psychiatric practice. METHODS: This manuscript proposes a system where sensors
      are utilised to devise an "early warning" system for patients with bipolar
      disorder. The system, containing wearable and environmental sensors, would
      collect behavioural data independent from the patient's self-report. To test the
      feasibility of the concept, a prototype system was devised, which was followed by
      trials including four healthy volunteers as well as a bipolar patient. RESULTS:
      The sensors utilised in the study yielded behavioural data which may be of
      significant use in detecting early effects of a bipolar episode. Basic processing
      performed on particular data inputs provided information about activity patterns
      in areas, which are usually strongly influenced by the course of Bipolar
      Disorder. CONCLUSIONS: The manuscript discusses the basic usage issues and other
      barriers which are to be tackled before technology-based approaches to mental
      care can be successfully rolled out and their true value appraised.

PMID- 22643030
TI  - Subtle memory and attentional deficits revealed in an Irish stroke patient sample
      using domain-specific cognitive tasks.
AB  - Stroke disrupts motor, sensory, and cognitive systems in survivors. Unlike in
      physical impairments, assessment of cognitive function is often inadequate, as no
      standardized procedure to monitor cognitive recovery post stroke exists. We
      evaluated a number of novel task-orientated tools designed to assess subtle
      cognitive deficits (including memory, attention, and executive functioning) in a
      sample of stroke patients. Although unimpaired on MMSE (Mini-Mental State
      Examination)-based indices of cognition, memory, and intelligence, stroke
      survivors were significantly impaired on tasks testing visual attention,
      spatial/relational processing, and associative memory. We recommend a
      standardized multidomain cognitive assessment and propose that cognitive deficits
      post stroke require in-depth assessment to inform patient-orientated
      rehabilitation.

PMID- 22643031
TI  - Peripheral and central mechanisms involved in the control of food intake by
      dietary amino acids and proteins.
AB  - The present review summarises current knowledge and recent findings on the
      modulation of appetite by dietary protein, via both peripheral and central
      mechanisms. Of the three macronutrients, proteins are recognised as the strongest
      inhibitor of food intake. The well-recognised poor palatability of proteins is
      not the principal mechanism explaining the decrease in high-protein (HP) diet
      intake. Consumption of a HP diet does not induce conditioned food aversion, but
      rather experience-enhanced satiety. Amino acid consumption is detected by
      multiple and redundant mechanisms originating from visceral (during digestion)
      and metabolic (inter-prandial period) sources, recorded both directly and
      indirectly (mainly vagus-mediated) by the central nervous system (CNS).
      Peripherally, the satiating effect of dietary proteins appears to be mediated by
      anorexigenic gut peptides, principally cholecystokinin, glucagon-like peptide-1
      and peptide YY. In the CNS, HP diets trigger the activation of noradrenergic and
      adrenergic neurons in the nucleus of the solitary tract and melanocortin neurons
      in the arcuate nucleus. Additionally, there is evidence that circulating leucine
      levels may modulate food intake. Leucine is associated with neural mechanisms
      involving mammalian target of rapamycin (mTOR) and AMP-activated protein kinase
      (AMPK), energy sensors active in the control of energy intake, at least in the
      arcuate nucleus of the hypothalamus. In addition, HP diets inhibit the activation
      of opioid and GABAergic neurons in the nucleus accumbens, and thus inhibit food
      intake by reducing the hedonic response to food, presumably because of their low
      palatability. Future studies should concentrate on studying the adaptation of
      different neural circuits following the ingestion of protein diets.

PMID- 22643032
TI  - Absorption, disposition, and pharmacokinetics of herbal medicines: what and how?

PMID- 22643033
TI  - Effectiveness of paced walking to music at home for patients with COPD.
AB  - The use of rhythmic music is beneficial in assisting with the exercise intensity
      at home. This paper investigated the effects of paced walking to music at home
      with an 80% VO(2) peak for patients with COPD. A prospective randomized clinical
      trial consisting of a treatment group (n = 20) assigned to a 12-week period of
      paced walking to music at home, while the patients in the control group (n = 21)
      were only given educational information. The treatment response was measured
      based on the patient's score in the maximal exercise capacity test using the
      incremental shuttle walking test (ISWT), lung function, health- related quality
      of life (HRQOL) using the Saint George Respiratory Questionnaire (SGRQ) and their
      health care utilization during baseline, 4, 8, 12 and 16 weeks. The treatment
      group increased their distance in the ISWT from 243.5 +/- 135.4 at baseline to 16
      weeks (306.0 +/- 107.3, p < 0.001), Borg RPE-D decreased from 2.2 +/- 1.3 at
      baseline to 0.8 +/- 1.1 (p < 0.001) at 16 weeks, and Borg RPE-L decreased from
      1.2 +/- 1.4 at baseline to 0.3 +/- 0.7 (p < 0.05) at 16 weeks, and improved all
      of the domains of the SGRQ, compared to the control group. The paced walking to
      music at home program helps patients to achieve a higher-intensity exercise. It
      is easily incorporated into the care of COPD patients, providing them with a
      convenient, safe and enjoyable exercise.

PMID- 22643034
TI  - 3-D QSAutogrid/R: an alternative procedure to build 3-D QSAR models.
      Methodologies and applications.
AB  - Since it first appeared in 1988 3-D QSAR has proved its potential in the field of
      drug design and activity prediction. Although thousands of citations now exist in
      3-D QSAR, its development was rather slow with the majority of new 3-D QSAR
      applications just extensions of CoMFA. An alternative way to build 3-D QSAR
      models, based on an evolution of software, has been named 3-D QSAutogrid/R and
      has been developed to use only software freely available to academics. 3-D
      QSAutogrid/R covers all the main features of CoMFA and GRID/GOLPE with
      implementation by multiprobe/multiregion variable selection (MPGRS) that improves
      the simplification of interpretation of the 3-D QSAR map. The methodology is
      based on the integration of the molecular interaction fields as calculated by
      AutoGrid and the R statistical environment that can be easily coupled with many
      free graphical molecular interfaces such as UCSF-Chimera, AutoDock Tools, JMol,
      and others. The description of each R package is reported in detail, and, to
      assess its validity, 3-D QSAutogrid/R has been applied to three molecular data
      sets of which either CoMFA or GRID/GOLPE models were reported in order to compare
      the results. 3-D QSAutogrid/R has been used as the core engine to prepare more
      that 240 3-D QSAR models forming the very first 3-D QSAR server ( www.3d-qsar.com
      ) with its code freely available through R-Cran distribution.

PMID- 22643035
TI  - Characterization of lung stem cell niches in a mouse model of bleomycin-induced
      fibrosis.
AB  - INTRODUCTION: In lung fibrosis, alveolar epithelium degenerates progressively.
      The goal of regenerative medicine is to aid repair and regeneration of the lost
      tissues in parenchyma and airways for which mobilization of tissue-resident
      endogenous or bone marrow-derived exogenous stem cells niches is a critical step.
      We used a lung injury model in mice to identify and characterize functional lung
      stem cells to clarify how stem cell niches counteract this degenerative process.
      METHODS: Short term assay (STA) - Bleomycin-induced lung inflammation and
      fibrosis were assessed in a model of idiopathic pulmonary fibrosis in wild-type
      (WT), gp91phox-/- (NOX-/-), and gp91phoxMMP-12 double knockout (DKO) mice on
      C57Bl/6 background and Hoechst 33322 dye effluxing side population (SP) cells
      characterized. Long term assay (LTA) - In a bleomycin induced lung fibrosis model
      in C57Bl6 mice, the number of mature cells were quantified over 7, 14, and 21
      days in bone marrow (BM), peripheral blood (PB), lung parenchyma (LP) and
      bronchoalveolar lavage (BAL) fluid by FACS. BrdU pulse chase experiment (10
      weeks) was used to identify label retaining cells (LRC). BrdU+ and BrdU- cells
      were characterized by hematopoietic (CD45+), pluripotency (TTF1+, Oct3/4+, SSEA
      3+, SSEA-4+, Sca1+, Lin-, CD34+, CD31+), and lung lineage-specific (SPC+, AQP-5+,
      CC-10+) markers. Clonogenic potential of LRCs were measured by CFU-c assays.
      RESULTS: STA- In lung, cellularity increased by 5-fold in WT and 6-fold in NOX-/-
      by d7. Lung epithelial markers were very low in expression in all SP flow sorted
      from lung of all three genotypes cultured ex vivo. (p < 0.01). Post-bleomycin,
      the SP in NOX-/- lung increased by 3.6-fold over WT where it increased by 20-fold
      over controls. Type I and II alveolar epithelial cells progressively diminished
      in all three genotypes by d21 post-bleomycin. D7 post-bleomycin, CD45+ cells in
      BALf in NOX-/- was 1.7-fold > WT, 57% of which were Mf that decreased by 67% in
      WT and 83% in NOX-/- by d21.LTA- Cellularity as a factor of time remained
      unchanged in BM, PB, LP and BAL fluid. BrdU+ (LRC) were the putative stem cells.
      BrdU+CD45+ cells increased by 0.7-fold and SPC+CC10+ bronchoalveolar stem cells
      (BASC), decreased by ~40-fold post-bleomycin. BrdU+VEGF+ cells decreased by 1.8
      fold while BrdU-VEGF+ cells increased 4.6-fold. Most BrdU- cells were CD45-. BrdU
      BASCs remained unchanged post-bleomycin. CFU-c of the flow-sorted BrdU+ cells
      remained similar in control and bleomycin-treated lungs. CONCLUSION: STA-
      Inflammation is a pre-requisite for fibrosis; SP cells, being the putative stem
      cells in the lungs, were increased (either by self renewal or by recruitment from
      the exogenous bone marrow pool) post-bleomycin in NOX-/- but not in DKO
      indicating the necessity of cross-talk between gp91phox and MMP-12 in this
      process; ex vivo cultured SP progressively lose pluripotent markers, notably BASC
      (SPC+CC10+) - significance is unknown. LTA- The increase in the hematopoietic
      progenitor pool in lung indicated that exogenous progenitors from circulation
      contribute to lung regeneration. Most non-stem cells were non-hematopoietic in
      origin indicating that despite tissue turnover, BASCs are drastically depleted
      possibly necessitating recruitment of progenitors from the hematopoietic pool.
      Loss of VEGF+ LRC may indicate a signal for progenitor mobilization from niches.
      BrdU- BASC population may be a small quiescent population that remains as a
      reserve for more severe lung injury. Increase in VEGF+ non-LRC may indicate a
      checkpoint to counterbalance the mobilization of VEGF+ cells from the stem cell
      niche.

PMID- 22643036
TI  - Percutaneous transhepatic balloon dilatation of benign bilioenteric strictures:
      long-term results in 110 patients.
AB  - BACKGROUND: Percutaneous transhepatic balloon dilatation is an alternative to
      surgery when benign bilioenteric strictures (BBES) are inaccessible to endoscopic
      treatment. Our primary objective was to report long-term patency of balloon
      dilated BBES. METHODS: A total of 110 consecutive patients with 155 BBES had
      percutaneous transhepatic complete drainage of all biliary territories, balloon
      dilatation, and catheter stenting. Intracorporeal electrohydraulic lithotripsy
      treated associated biliary stones. Biliary drains were removed when no residual
      balloon waists were observed on at least 2 consecutive sessions, 6 weeks apart.
      RESULTS: A total of 109 of 110 patients had complete drainage. Forty-five
      patients had successfully treated associated stones. Eleven patients had short
      term complications. No patients died. The median follow-up period was 59 months
      (range, .5-278 mo). Twenty-three patients were lost to follow-up evaluation.
      Thirteen patients had recurrent biliary obstruction (15%). Life-table analysis
      showed 90.9% bilioenteric patency after 2,697 days. CONCLUSIONS: Percutaneous
      balloon dilatation and calibration of BBES provides acceptable morbidity and low
      long-term stricture recurrence.

PMID- 22643037
TI  - Commentary on "The outcome after stent placement or surgery as the initial
      treatment for obstructive primary tumor in patients with stage IV colon cancer".

PMID- 22643038
TI  - Closed claim review from a single carrier in New York: the real costs of
      malpractice in surgery and factors that determine outcomes.
AB  - INTRODUCTION: We postulated that a closed claim review of surgical cases would
      identify not only the quality of care elements but also factors that will predict
      successful legal outcomes. METHODS: One hundred eighty-seven closed surgical
      cases from a single carrier, which insured physicians practicing in 4 university
      hospitals in New York State, were reviewed, cataloged, and analyzed. RESULTS:
      Most suits occurred during midcareer and routine operations. Seventy-three
      percent of cases were won. The average payment and expenses per case were
      $220,846 +/- $38,984 and $40,175 +/- $4,204, respectively. Poor communication was
      identified in 24% of cases and was a predictor of a negative outcome (41% lost, P
      < .05), as was inadequate attending supervision (46% lost, P < .05). Expert
      reviews incriminated or exculpated physician defendants in 85 cases, which
      affected the outcome and cost. The quality of the physician defendant as a
      witness also affected the outcome. CONCLUSIONS: Most surgical malpractice claims
      are won. Although supervision, communication, and aggressive risk management are
      important, the use of quality experts and establishing credibility of the
      physician defendant are critical for successful legal outcome.

PMID- 22643039
TI  - Child temperament, parent emotions, and perceptions of the child's feeding
      experience.
AB  - BACKGROUND: Associations between parent and child characteristics and how they
      influence the approach parents take toward children in the feeding environment
      have not been examined extensively, especially in low-income minority families
      who are at a higher risk for obesity. The primary aim of the study was to examine
      positive and negative parent emotions as potential mediators of the relationship
      between child temperament and parents' perceptions of strategy effectiveness and
      problems encountered in feeding children fruit and vegetables. METHODS:
      Participants were low-income families (n = 639, 73% minority, children aged 3-5
      years) participating in Head Start programs in two states. Parents completed the
      Children's Behavior Questionnaire (CBQ), Positive and Negative Affect Schedule
      (PANAS), and measures of strategy effectiveness (teachable moments, practical
      methods, restriction, and enhanced availability) and problems encountered
      (vegetable characteristics, child attributions for dislike, external influences,
      and parental demands) in feeding children fruit and vegetables. RESULTS: Positive
      parent emotions partially mediated the relationship between child Effortful
      Control and strategy effectiveness and fully mediated the relationship between
      Surgency and strategy effectiveness. Although negative parent emotions were
      associated with increased perception of problems in feeding children fruit and
      vegetables, the relationship between Negative Affectivity and problems in feeding
      was partially mediated by negative parent emotions. CONCLUSIONS: Positive parent
      emotions facilitated perceived effectiveness of feeding strategies, with child
      Effortful Control and Surgency instrumental to this process. Understanding
      mechanisms in parent-child feeding is important when developing interventions
      designed to promote healthy child eating behaviors.

PMID- 22643040
TI  - Abdominal Colpopexy: Comparison of Endoscopic Surgical Strategies (ACCESS).
AB  - INTRODUCTION: Robotic assistance during laparoscopic surgery for pelvic organ
      prolapse rapidly disseminated across the United States without level I data to
      support its benefit over traditional open and laparoscopic approaches [1]. This
      manuscript describes design and methodology of the Abdominal Colpopexy:
      Comparison of Endoscopic Surgical Strategies (ACCESS) Trial. METHODS: ACCESS is a
      randomized comparative effectiveness trial enrolling patients at two academic
      teaching facilities, UCLA (Los Angeles, CA) and Loyola University (Chicago, IL).
      The primary aim is to compare costs of robotic assisted versus pure laparoscopic
      abdominal sacrocolpopexy (RASC vs LASC). Following a clinical decision for
      minimally-invasive abdominal sacrocolpopexy (ASC) and research consent,
      participants with symptomatic stage>=II pelvic organ prolapse are randomized to
      LASC or RASC on the day of surgery. Costs of care are based on each patient's
      billing record and equipment costs at each hospital. All costs associated with
      surgical procedure including costs for robot and initial hospitalization and any
      re-hospitalization in the first 6weeks are compared between groups. Secondary
      outcomes include post-operative pain, anatomic outcomes, symptom severity and
      quality of life, and adverse events. Power calculation determined that 32 women
      in each arm would provide 95% power to detect a $2500 difference in total
      charges, using a two-sided two sample t-test with a significance level of 0.05.
      RESULTS: Enrollment was completed in May 2011. The 12-month follow-up was
      completed in May 2012. CONCLUSIONS: This is a multi-center study to assess cost
      as a primary outcome in a comparative effectiveness trial of LASC versus RASC.

PMID- 22643042
TI  - The effects of fatty deposits on the accuracy of the Fibroscan(r) liver transient
      elastography ultrasound system.
AB  - A new generation of ultrasound transient elastography (TE) systems have emerged
      which exploit the well-known correlation between the liver's pathological and
      mechanical properties through measurements of the Young's elastic modulus;
      however, little work has been carried out to examine the effect that fatty
      deposits may have on the TE measurement accuracy. An investigation was carried
      out on the effects on the measurement accuracy of a TE ultrasound system, the
      Fibroscan(r), caused by overlaying fat layers of varying thickness on healthy
      liver-mimicking phantoms, simulating in vivo conditions for obese patients.
      Furthermore, a steatosis effect similar to that in non-alcoholic fatty liver
      disease (NAFLD) and alcoholic liver disease (ALD) was simulated to investigate
      its effect on the TE system. A range of novel elastography fat-mimicking
      materials were developed using 6-10 wt% poly(vinyl alcohol) cryogel capable of
      achieving a range of acoustic velocities (1482-1530 m s(-1)) and attenuation
      coefficients (0.4-1 dB MHz(-1) cm(-1)) for simulating different liver states.
      Laboratory-based acoustic velocities and attenuation coefficients were measured
      while the Young's modulus was established through a gold standard compression
      testing method. A significant variation of the Young's elastic modulus was
      measured in healthy phantoms with overlaying fat layers of thicknesses exceeding
      45 mm, impinging on the scanners region of interest, overestimating the
      compression tested values by up to 11 kPa in some cases. Furthermore,
      Fibroscan(r) measurements of the steatosis phantoms showed a consistent
      overestimation (~54%), which strongly suggests that the speed of sound mismatch
      between that of liver tissue and that assumed by the scanner is responsible for
      the high clinical cut-offs established in the case of ALD and NAFLD.

PMID- 22643041
TI  - Affective engagement for facial expressions and emotional scenes: the influence
      of social anxiety.
AB  - Pictures of emotional facial expressions or natural scenes are often used as cues
      in emotion research. We examined the extent to which these different stimuli
      engage emotion and attention, and whether the presence of social anxiety symptoms
      influences responding to facial cues. Sixty participants reporting high or low
      social anxiety viewed pictures of angry, neutral, and happy faces, as well as
      violent, neutral, and erotic scenes, while skin conductance and event-related
      potentials were recorded. Acoustic startle probes were presented throughout
      picture viewing, and blink magnitude, probe P3 and reaction time to the startle
      probe also were measured. Results indicated that viewing emotional scenes
      prompted strong reactions in autonomic, central, and reflex measures, whereas
      pictures of faces were generally weak elicitors of measurable emotional response.
      However, higher social anxiety was associated with modest electrodermal changes
      when viewing angry faces and mild startle potentiation when viewing either angry
      or smiling faces, compared to neutral. Taken together, pictures of facial
      expressions do not strongly engage fundamental affective reactions, but these
      cues appeared to be effective in distinguishing between high and low social
      anxiety participants, supporting their use in anxiety research.

PMID- 22643043
TI  - Rhodiola rosea for physical and mental fatigue: a systematic review.
AB  - BACKGROUND: Rhodiola rosea (R. rosea) is grown at high altitudes and northern
      latitudes. Due to its purported adaptogenic properties, it has been studied for
      its performance-enhancing capabilities in healthy populations and its therapeutic
      properties in a number of clinical populations. To systematically review evidence
      of efficacy and safety of R. rosea for physical and mental fatigue. METHODS: Six
      electronic databases were searched to identify randomized controlled trials
      (RCTs) and controlled clinical trials (CCTs), evaluating efficacy and safety of
      R. rosea for physical and mental fatigue. Two reviewers independently screened
      the identified literature, extracted data and assessed risk of bias for included
      studies. RESULTS: Of 206 articles identified in the search, 11 met inclusion
      criteria for this review. Ten were described as RCTs and one as a CCT. Two of six
      trials examining physical fatigue in healthy populations report R. rosea to be
      effective as did three of five RCTs evaluating R. rosea for mental fatigue. All
      of the included studies exhibit either a high risk of bias or have reporting
      flaws that hinder assessment of their true validity (unclear risk of bias).
      CONCLUSION: Research regarding R. rosea efficacy is contradictory. While some
      evidence suggests that the herb may be helpful for enhancing physical performance
      and alleviating mental fatigue, methodological flaws limit accurate assessment of
      efficacy. A rigorously-designed well reported RCT that minimizes bias is needed
      to determine true efficacy of R. rosea for fatigue.

PMID- 22643044
TI  - Performance of emergency physicians utilizing a video-assisted semi-rigid
      fiberoptic stylet for intubation of a difficult airway in a high-fidelity
      simulated patient: a pilot study.
AB  - BACKGROUND: This study was designed to evaluate emergency physician success and
      satisfaction using a video-assisted semi-rigid fiberoptic stylet, the Clarus
      Video System (CVS), during a simulated difficult airway scenario. FINDINGS:
      Emergency physicians (EPs) of all levels were first shown a brief slide show and
      three example videos, and then given 20 min to practice intubating a mannequin
      using both the CVS and standard direct laryngoscopy (DL). The mannequin was then
      placed in a c-collar and set to simulate an apneic patient with an edematous
      tongue and trismus. Each EP was given up to three timed attempts with each
      technique. They rated their satisfaction with the CVS, usefulness for their
      practice, and the effectiveness of the tutorial. Direct laryngoscopy had a 65%
      success rate on the first attempt, 20% on the second, and 15% required three or
      more. The CVS had a 100% success rate with a single attempt. Average time for
      independent DL attempts was 43.41 s (SD = +/-26.82) and 38.71 s (SD = +/-34.14)
      with CVS. Cumulative attempt times were analyzed and compared (DL = 74.55 +/-
      68.40 s and CVS = 38.71 +/- 34.14 s; p = 0.028). EPs rated their satisfaction
      with, and usefulness of, the CVS as >=6 out of 10. CONCLUSION: Emergency
      physicians were able to successfully intubate a simulated difficult airway model
      on the first attempt 100% of the time. Emergency physicians were satisfied with
      the CVS and felt that it would be useful in their practice.

PMID- 22643045
TI  - Regulation of inositol 1,4,5-triphosphate receptor, type 1 (IP3R1) in
      hypoxic/reperfusion injury of white matter.
AB  - OBJECTIVE: Calcium overloading is responsible for initiating the cell death in
      neuronal tissue after hypoxic injury. Inositol 1,4,5-triphosphate receptors
      (IP3Rs) is an important calcium channel which regulates cellular calcium
      homeostasis. IP3R1 is widely expressed in brain  and spinal tissue. In the
      present study, we have studied the regulation of IP3R1 in hypoxic/reperfusion
      injury of spinal cord dorsal column in vitro. METHODS: Dorsal columns were
      isolated from the spinal cord of adult rats and injury was induced by exposing to
      hypoxic condition  for 1 hour. After injury, reperfusion was carried out for 0,
      2, 4, and 8 hours. Tissues were collected and processed for western blotting,
      immunohistochemistry and real-time PCR. RESULTS: In the present study, we have
      found increased expression of IP3R1 after hypoxic/reperfusion  injury of spinal
      cord dorsal column in vitro. Maximum expression of IP3R1 has been seen at 4 hours
      after hypoxia. Double immunofluorescence studies show the localization of IP3R1
      in axons and astrocytes. Further identifying the signaling pathway involved in
      the regulation, we found  Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)
      inhibitor KN-62 and c-Jun N-terminal kinase (JNK) inhibitor SP600125 reduced the
      expression of IP3R1 suggesting the role of CaMKII and JNK in the regulation of
      IP3R1 expression. We did not find role of ERK and p38 in the regulation  IP3R1
      expression in hypoxic/reperfusion injury of dorsal column in vitro. DISCUSSION:
      The result presented in this study showed that IP3R1 expression is increased in
      hypoxic/reperfusion injury of spinal cord white matter and it is regulated by the
      CaMKII-JNK pathway.

PMID- 22643046
TI  - NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP
      9 upregulation in brain astrocytes.
AB  - BACKGROUND: Lipoteichoic acid (LTA) is a component of gram-positive bacterial
      cell walls and may be elevated in the cerebrospinal fluid of patients suffering
      from meningitis. Among matrix metalloproteinases (MMPs), MMP-9 has been observed
      in patients with brain inflammatory diseases and may contribute to the pathology
      of brain diseases. Moreover, several studies have suggested that increased
      oxidative stress is implicated in the pathogenesis of brain inflammation and
      injury. However, the molecular mechanisms underlying LTA-induced redox signal and
      MMP-9 expression in brain astrocytes remain unclear. OBJECTIVE: Herein we
      explored whether LTA-induced MMP-9 expression was mediated through redox signals
      in rat brain astrocytes (RBA-1 cells). METHODS: Upregulation of MMP-9 by LTA was
      evaluated by zymographic and RT-PCR analyses. Next, the MMP-9 regulatory pathways
      were investigated by pretreatment with pharmacological inhibitors or transfection
      with small interfering RNAs (siRNAs), Western blotting, and chromatin
      immunoprecipitation (ChIP)-PCR and promoter activity reporter assays. Moreover,
      we determined the cell functional changes by migration assay. RESULTS: These
      results showed that LTA induced MMP-9 expression via a PKC(alpha)-dependent
      pathway. We further demonstrated that PKCalpha stimulated p47phox/NADPH oxidase 2
      (Nox2)-dependent reactive oxygen species (ROS) generation and then activated the
      ATF2/AP-1 signals. The activated-ATF2 bound to the AP-1-binding site of MMP-9
      promoter, and thereby turned on MMP-9 gene transcription. Additionally, the co
      activator p300 also contributed to these responses. Functionally, LTA-induced MMP
      9 expression enhanced astrocytic migration. CONCLUSION: These results
      demonstrated that in RBA-1 cells, activation of ATF2/AP-1 by the PKC(alpha)
      mediated Nox(2)/ROS signals is essential for upregulation of MMP-9 and cell
      migration enhanced by LTA.

PMID- 22643047
TI  - Local suppression of IL-21 in submandibular glands retards the development of
      Sjogren's syndrome in non-obese diabetic mice.
AB  - BACKGROUND: The aim of this study was to verify the validity of IL-21 local
      suppression in submandibular glands of preventing the development of Sjogren's
      syndrome in non-obese diabetic (NOD) mice and figure out the mechanism. METHODS:
      IL-21 levels in submandibular glands were suppressed by ductal cannulation of IL
      21 shRNA lentivirus. Then, saliva flow rates (SFR) and histopathologic changes of
      submandibular glands were measured to assess the severity of disease development.
      Real-time PCR, flow cytometry, and immunohistochemistry were used to detect the
      changes of T helper cells and related cytokines. RESULTS: The reduction in SFRs
      in NOD mice was significantly alleviated from 9 to 17 weeks of age along with the
      suppression of IL-21 in submandibular glands. Lymphocytic infiltration was also
      milder than control NOD mice. Moreover, the lower level of IL-21 led to the down
      regulation of follicular helper T (Tfh) cells. CONCLUSIONS: Local suppression of
      IL-21 in submandibular glands could retard the development of Sjogren's syndrome
      in NOD mice. IL-21 might contribute to the development of B-cell disorder in
      Sjogren's syndrome via Tfh cells pathway.

PMID- 22643048
TI  - Paclitaxel and cetuximab combination efficiency after the failure of a platinum
      based chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma.
AB  - The addition of cetuximab (CTX) to the combination of cisplatin and 5
      fluorouracil increases the overall survival (OS) in recurrent/metastatic head and
      neck squamous cell carcinoma. Only a few patients are eligible for this treatment
      because of its toxicity. The combination of CTX and paclitaxel (TXL) could be
      included in sequential treatment strategies. Patients were treated with CTX
      (400/250 mg/m) and TXL (60-80 mg/m) weekly until disease progression or
      unacceptable toxicity. Efficacy and safety outcomes were determined
      retrospectively. A total of 42 patients were included in this analysis. The
      overall response rate was 38% [95% confidence interval (CI); 23-53%]. The disease
      control rate with TXL and CTX combination was 74%. Seven (17%) patients
      progressed before the first evaluation. The median progression-free survival was
      3.9 months [95% CI; 3.1-4.7 months] and the median OS was 7.6 months [95% CI; 5.3
      9.9 months]. Neurotoxicity and skin rash were the most frequent grade>=2
      toxicities, reported in 17 and 12% of patients, respectively. Previous
      chemotherapy seems to be associated with a lower response rate and progression
      free survival but not with the OS. The combination of CTX and TXL was an active
      and well-tolerated treatment in this series of patients with a poor prognosis and
      who were mostly symptomatic.

PMID- 22643049
TI  - Asymmetric interference associated with force amplitude and hand dominance in
      bimanual constant isometric force.
AB  - This study investigated the asymmetry of bilateral interference in relation to
      the relative difference of force amplitude between hands and the hand dominance.
      In Experiment 1, one hand produced a fixed constant force of 5% maximum voluntary
      contraction (MVC) while the other hand produced different constant forces of 5%,
      20%, and 50% MVC in blocked conditions. Asymmetric interference in force
      amplitude alone was evident in that the hand producing the fixed low force showed
      a stronger interference than the hand performing the higher force. Asymmetric
      interference in hand dominance was also found in that more interference was
      observed when the nondominant left hand produced the higher force, a finding that
      does not support the hemisphere specialization hypothesis. Experiment 2 was
      performed to rule out the fixed force level interpretation compared with the low
      force level account and the fixed force was set at 50% MVC. The results were
      consistent with the findings in Experiment 1 showing asymmetric interference with
      force amplitude rather than with fixed force level. The findings revealed that
      without a timing constraint the task demand associated with force amplitude alone
      can induce the asymmetric bilateral interference. The external task asymmetry and
      intrinsic asymmetry of the organism interact and influence the bimanual force
      coordination and control patterns.

PMID- 22643050
TI  - The impact of loneliness on self-rated health symptoms among victimized school
      children.
AB  - BACKGROUND: Loneliness is associated with peer victimization, and the two adverse
      experiences are both related to ill health in childhood and adolescence. There
      is, however, a lack of knowledge on the importance of loneliness among victimized
      children. Therefore, possible modifying effects of loneliness on victimized
      school children's self-rated health were assessed. METHODS: A population based
      cross-section study included 419 children in grades 1-10 from five schools. The
      prevalence of loneliness and victimization across grades was analyzed by linear
      test for trend, and associations of the adverse experiences with four health
      symptoms (sadness, anxiety, stomach ache, and headache) were estimated by
      logistic regression. RESULTS: In crude regression analysis, both victimization
      and loneliness showed positive associations with all the four health symptoms.
      However, in multivariable analysis, the associations of victimization with health
      symptoms were fully attenuated except for headache. In contrast, loneliness
      retained about the same strength of associations in the multivariable analysis as
      in the crude analysis. More detailed analyses demonstrated that children who
      reported both victimization and loneliness had three to seven times higher
      prevalence of health symptoms compared to children who reported neither
      victimization nor loneliness (the reference group). Rather surprisingly,
      victimized children who reported no loneliness did not have any higher prevalence
      of health symptoms than the reference group, whereas lonely children without
      experiences of victimization had almost the same prevalence of health symptoms
      (except for stomach ache) as children who were both victimized and lonely.
      CONCLUSIONS: Adverse effects of loneliness need to be highlighted, and for
      victimized children, experiences of loneliness may be an especially harsh risk
      factor related to ill health.

PMID- 22643051
TI  - A fetus with hemifacial microsomia and sirenomelia. The same mesodermal defect
      spectrum?
AB  - Sirenomelia is the most severe malformation complex affecting the human caudal
      pole, although its etiology is unclear, a primary defect of blastogenesis has
      been proposed. Studies consider sirenomelia as the most severe form of caudal
      dysgenesis, VACTERL association, or axial mesodermal dysplasia, although others
      still support the idea of a different pathologic entity. We report the prenatal,
      clinical, and pathologic features of a fetus with cleft lip and palate, microtia,
      cardiac, renal and intestinal malformations, radial aplasia, and sirenomelia.
      Karyotype, chromosomal breakage studies, and SHH sequence analysis were normal.
      The occurrence of cephalic, midline-paramedial, and caudal malformations in the
      same patient imply the diagnosis of hemifacial microsomia and sirenomelia. These
      entities are part of the same mesodermal malformation spectrum and the clinical
      presentation depends on environmental and genetic interactions in embrionic
      development. Future clinical and genome wide studies will help to better
      delineate this spectrum.

PMID- 22643052
TI  - In vivo controlled release and prolonged antitumor effects of 2-methoxyestradiol
      solid lipid nanoparticles incorporated into a thermosensitive hydrogel.
AB  - A two-phase delivery system involving local injections of solid lipid
      nanoparticles (SLNs) -loaded hydrogel was developed using 2-methoxyestradiol as a
      model anticancer drug. This approach improves the effectiveness of conventional
      treatments for subcutaneous tumors and avoids that solid lipid nanoparticles are
      rapidly cleared from the circulation following systemic administration. The
      specific aim of the study presented in this article was to investigate the in
      vivo release, delivery and antitumor effects of 2-ME SLNs entrapped in a
      hydrogel. The results indicated that the hydrogel could deliver fluorescence
      marked SLNs to tumor masses and cancer cells, exhibiting a controlled release of
      2-ME SLNs over 46 days following a zero-order model. After treatment with the 2
      ME SLN-loaded hydrogel, BALB/c mice that had been inoculated with syngeneic 4T1
      breast cancer cells displayed significantly more tumor growth suppression for at
      least 21 days than those treated with a hydrogel containing the free drug, which
      was consistent with the in vitro cytotoxicity of 2-ME SLNs. This experiment
      demonstrated the efficacy of the hydrogel as a depot of 2-ME SLNs. Additionally,
      the mice treated with the hydrogel did not exhibit a loss of body weight or
      abnormal levels of white blood cells compared to the control group. These
      experiments demonstrated the potential value of 2-ME SLN hydrogel local
      injections as a safer and more effective method for the chemotherapy of
      subcutaneous tumors.

PMID- 22643053
TI  - The effect of deacetylated gellan gum on aesculin distribution in the posterior
      segment of the eye after topical administration.
AB  - The aim of the present work was to evaluate the effect of deacetylated gellan gum
      on delivering hydrophilic drug to the posterior segment of the eye. An aesculin
      containing in situ gel based on deacetylated gellan gum (AG) was prepared and
      characterized. In vitro corneal permeation across isolated rabbit cornea of
      aesculin between AG and aesculin solution (AS) was compared. The results showed
      that deacetylated gellan gum promotes corneal penetration of aesculin.
      Pharmacokinetics and ocular tissue distribution of aesculin after topical
      administration in rabbit eye showed that AG greatly improved aesculin
      accumulation in posterior segmentsrelative to AS, which was probably attributed
      to conjunctivital/sclera pathway. The area-under-the-curve (AUC) for AG in
      aqueous humor, choroid-retina, sclera and iris-ciliary body were significantly
      larger than those of AS. AG can be used as a potential carrier for broading the
      application of aesculin.

PMID- 22643054
TI  - A novel synthetic derivative of human erythropoietin designed to bind to
      glycosaminoglycans.
AB  - To synthesize long-acting and antiangiogenic erythropoietin to be clinically
      applied for treatment of patients with solid tumors, we synthesized a hybrid
      molecule of human erythropoietin added onto the C-terminus with a heparin-binding
      motif of human PLGF-2 to develop a novel derivative of long-acting and
      antiangiogenic erythropoietin: heparin-binding erythropoietin (HEPO), and studied
      the characteristics of this novel erythropoietin derivative. HEPO cDNA was
      synthesized, expressed in insect cells, and the protein was purified using a
      heparin-sepharose affinity column. The erythropoietic and angiogenic effects of
      the partially purified protein were analyzed in vitro and in vivo. The
      erythropoietic activity of the protein was equivalent to natural EPO in vitro. In
      vivo administration of the protein to mice revealed its long-acting
      erythropoietic activity as expected. Administration of the protein inhibited
      angiogenesis in a mouse limb ischemia model. In conclusion, the heparin-binding
      motif of PLGF-2 may act as, so to speak, a superendostatin. This novel long
      acting erythropoietin derivative may have an advantage to inhibit tumor growth
      while preserving hematopoietic and tissue-protective effects.

PMID- 22643055
TI  - Preparation and evaluation of folate-modified cationic pluronic micelles for
      poorly soluble anticancer drug.
AB  - The aim of this study was to construct novel targeting polymeric micelles. Folate
      Poly (ethylenimine)-Pluronic copolymers were synthesized. A paclitaxel (PTX)
      loaded mixed micelles consisting of Folate-Poly (ethylenimine)-Pluronic and
      Pluronic L121 copolymers have been developed. The mixed micelles showed nano
      sized spherical morphology. The solubilization capacity of the mixed micelles was
      higher than Folate-Poly (ethylenimine)-Pluronic micelles because L121 has high
      solubilization capacity. MTT colorimetric test revealed that PTX in Folate-Poly
      (ethylenimine)-Pluronic micelles demonstrated the maximum anticancer activity.
      Pluronic-poly (ethylenimine) micelles and folate-modified Pluronic
      poly(ethylenimine) micelles showed a marked increase of cellular accumulation
      compared with Pluronic P123 micelles. The biodistribution and retention of
      intravenously (i.v.) administered micelles to rats were determined. Folate-Poly
      (ethylenimine)-Pluronic micelles demonstrated enhanced pulmonary retention in
      rats after injection when compared to Pluronic P123 micelles.

PMID- 22643057
TI  - Novel oral delivery system of indomethacin by solidified mPEG-PDLLA micelles: in
      vivo study.
AB  - To administer indomethacin (IND) orally using polymeric micelles, IND loaded
      solidified polymeric micelles (IND-SPM) were prepared and evaluated for their in
      vitro and in vivo characteristics. IND and methoxy-poly(ethylene glycol) poly(d,
      l-lactide) copolymer (mPEG-PDLLA) were dissolved in acetone followed by the
      addition of an equivalent amount of polyplasdone XL-10 and stirred to obtain a
      suspension. Afterwards, acetone was completely evaporated. It was found that IND
      SPM generates small polymeric micelles of 18.1 nm. Moreover, the solubility of
      IND at pH 6.8 increased 4.6-folds, and more than 90% of IND in 20 mg of IND-SPM
      was dissolved in 250 mL SIF pH 6.8 within 30 min. Pharmacokinetic parameters in
      fasted rats showed that IND-SPM 1:3 resulted in 3-folds increase of AUC and
      C(max) compared to commercial IND. mPEG-PDLLA micelles were found to be efficient
      carriers for oral administration of IND as solid dosage forms by adsorption on
      polyplasdone XL-10.

PMID- 22643056
TI  - Quantum rods as nanocarriers of gene therapy.
AB  - Both antisense oligonucleotides (ASODN) and small interfering RNA (siRNA) have
      enormous potential to selectively silence specific cancer-related genes and could
      therefore be developed to be important therapeutic anti-cancer drugs. The use of
      nanotechnology may allow for significant advancement of the therapeutic potential
      of ASODN and siRNA, due to improved pharmacokinetics, bio-distribution and tissue
      specific targeted therapy. In this mini-review, we have discussed the advantages
      of using a nanocarrier such as a multimodal quantum rod (QR) complexed with siRNA
      for gene delivery. Comparisons are made between ASODN and siRNA therapeutic
      efficacies in the context of cancer and the enormous application potential of
      nanotechnology in oncotherapy is discussed. We have shown that a QR-interleukin-8
      (IL-8) siRNA nanoplex can effectively silence IL-8 gene expression in the PC-3
      prostate cancer cells with no significant toxicity. Thus, nanocarriers such as
      QRs can help translate the potent effects of ASODN/siRNA into a clinically viable
      anti-cancer therapy. Drug delivery for cancer therapy, with the aid of
      nanotechnology is one of the major translational aspects of nanomedicine, and
      efficient delivery of chemotherapy drugs and gene therapy drugs or their co
      delivery continue to be a major focus of nanomedicine research.

PMID- 22643058
TI  - Comparison of alphabetical versus categorical display format for medication order
      entry in a simulated touch screen anesthesia information management system: an
      experiment in clinician-computer interaction in anesthesia.
AB  - BACKGROUND: Anesthesia information management system (AIMS) records should be
      designed and configured to facilitate the accurate and prompt recording of
      multiple drugs administered coincidentally or in rapid succession. METHODS: We
      proposed two touch-screen display formats for use with our department's new EPIC
      touch-screen AIMS. In one format, medication "buttons" were arranged in
      alphabetical order (i.e. A-C, D-H etc.). In the other, buttons were arranged in
      categories (Common, Fluids, Cardiovascular, Coagulation etc.). Both formats were
      modeled on an iPad screen to resemble the AIMS interface. Anesthesia residents,
      anesthesiologists, and Certified Registered Nurse Anesthetists (n = 60) were then
      asked to find and touch the correct buttons for a series of medications whose
      names were displayed to the side of the entry screen. The number of entries made
      within 2 minutes was recorded. This was done 3 times for each format, with the
      1st format chosen randomly. Data were analyzed from the third trials with each
      format to minimize differences in learning. RESULTS: The categorical format had a
      mean of 5.6 more drugs entered using the categorical method in two minutes than
      the alphabetical format (95% confidence interval [CI] 4.5 to 6.8, P < 0.0001).
      The findings were the same regardless of the order of testing (i.e. alphabetical
      categorical vs. categorical - alphabetical) and participants' years of clinical
      experience. Most anesthesia providers made no (0) errors for most trials (N =
      96/120 trials, lower 95% limit 73%, P < 0.0001). There was no difference in error
      rates between the two formats (P = 0.53). CONCLUSIONS: The use of touch-screen
      user interfaces in healthcare is increasingly common. Arrangement of drugs names
      in a categorical display format in the medication order-entry touch screen of an
      AIMS can result in faster data entry compared to an alphabetical arrangement of
      drugs. Results of this quality improvement project were used in our department's
      design of our final intraoperative electronic anesthesia record. This testing
      approach using cognitive and usability engineering methods can be used to
      objectively design and evaluate many aspects of the clinician-computer
      interaction in electronic health records.

PMID- 22643059
TI  - The association of biological and psychological attributions for depression with
      social support seeking intentions in individuals with depressive symptoms.
AB  - BACKGROUND: Research suggests that biological and psychological attributions for
      depression are related to professional help-seeking, but the association of these
      attributions with informal support seeking in social relationships is unknown. As
      social support is linked with recovery from depression and a lower likelihood of
      experiencing future episodes of depression, it is important to understand factors
      that influence an individual's decision to seek social support. AIMS: The present
      study examined depressed individuals' own attributions for their depressive
      symptoms (i.e. personal attributions), perceptions of a friend's attributions for
      these symptoms (i.e. perceived attributions), and the depressed individuals'
      willingness to seek social support from that friend. METHOD: Eighty-six
      individuals experiencing at least mild depressive symptoms completed self-report
      measures of personal attributions, perceived attributions, and a social support
      seeking intentions scale. RESULTS: Participants' own attributions for depressive
      symptoms were unrelated to their willingness to seek social support. In contrast,
      perceived biological attributions were related to greater help-seeking
      intentions, whereas perceived psychological attributions were associated with
      lower support seeking intentions. CONCLUSIONS: These results suggest that
      decisions to seek social support are more influenced by perceptions of others'
      beliefs about depression than one's own beliefs.

PMID- 22643060
TI  - The experimental uncertainty of heterogeneous public K(i) data.
AB  - The maximum achievable accuracy of in silico models depends on the quality of the
      experimental data. Consequently, experimental uncertainty defines a natural upper
      limit to the predictive performance possible. Models that yield errors smaller
      than the experimental uncertainty are necessarily overtrained. A reliable
      estimate of the experimental uncertainty is therefore of high importance to all
      originators and users of in silico models. The data deposited in ChEMBL was
      analyzed for reproducibility, i.e., the experimental uncertainty of independent
      measurements. Careful filtering of the data was required because ChEMBL contains
      unit-transcription errors, undifferentiated stereoisomers, and repeated citations
      of single measurements (90% of all pairs). The experimental uncertainty is
      estimated to yield a mean error of 0.44 pK(i) units, a standard deviation of 0.54
      pK(i) units, and a median error of 0.34 pK(i) units. The maximum possible squared
      Pearson correlation coefficient (R(2)) on large data sets is estimated to be
      0.81.

PMID- 22643061
TI  - Kidney proteome changes provide evidence for a dynamic metabolism and regional
      redistribution of plasma proteins during torpor-arousal cycles of hibernation.
AB  - Hibernating ground squirrels maintain homeostasis despite extreme physiological
      challenges. In winter, these circannual hibernators fast for months while cycling
      between prolonged periods of low blood flow and body temperature, known as
      torpor, and short interbout arousals (IBA), where more typical mammalian
      parameters are rapidly restored. Here we examined the kidney proteome for changes
      that support the dramatically different physiological demands of the hibernator's
      year. We identified proteins in 150 two-dimensional gel spots that altered by at
      least 1.5-fold using liquid chromatography and tandem mass spectrometry. These
      data successfully classified individuals by physiological state and revealed
      three dynamic patterns of relative protein abundance that dominated the
      hibernating kidney: 1) a large group of proteins generally involved with
      capturing and storing energy were most abundant in summer; 2) a select subset of
      these also increased during each arousal from torpor; and 3) 14 spots increased
      in torpor and early arousal were enriched for plasma proteins that enter cells
      via the endocytic pathway. Immunohistochemistry identified alpha(2)-macroglobulin
      and albumin in kidney blood vessels during late torpor and early arousal; both
      exhibited regional heterogeneity consistent with highly localized control of
      blood flow in the glomeruli. Furthermore, albumin, but not alpha(2)
      macroglobulin, was detected in the proximal tubules during torpor and early
      arousal but not in IBA or summer animals. Taken together, our findings indicate
      that normal glomerular filtration barriers remain intact throughout torpor
      arousal cycles but endocytosis, and hence renal function, is compromised at low
      body temperature during torpor and then recovers with rewarming during arousal.

PMID- 22643062
TI  - Celebrating physiological genomics at the 125th anniversary of the American
      Physiological Society.

PMID- 22643063
TI  - Filter calculation for x-ray tomosynthesis reconstruction.
AB  - Filtered backprojection reconstruction is an efficient image reconstruction
      method which is widely used in CT and 3D x-ray imaging. The way data have to be
      filtered depends on the acquisition geometry and the number of projections
      (views) which were acquired. For standard geometries like circle or helix it is
      known how to effectively filter the data. But there are acquisition geometries
      for which the application of standard filters yields poor results, e.g. in
      situations where the number of views is very small or for a limited angular
      range. In tomosynthesis, both conditions apply, i.e. the number of projections is
      typically very small and, moreover, the angular coverage is much less than 180
      degrees . This paper proposes a new method to design effective filters which are
      specific for the acquisition geometry. Examples from x-ray tomosynthesis are
      utilized to demonstrate the excellent performance of the proposed method.

PMID- 22643064
TI  - Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon
      cancer cell lines.
AB  - BACKGROUND: Astrocyte elevated gene 1 (AEG-1), an important oncogene, has been
      shown to be overexpressed in several types of cancers. In colorectal cancer
      (CRC), the protein level of AEG-1 is up-regulated in tumour tissue compared to
      normal mucosa, showing prognostic significance. Since little is known about the
      transcriptional level of AEG-1 expression and its biological pathway in CRC the
      aim of the present study was to examine the relationship of AEG-1 mRNA
      expression, the protein level and clinicopathological variables as well as its
      biology pathway in CRC. MATERIAL AND METHODS: The mRNA expression of AEG-1 was
      analysed by qPCR in fresh frozen patient samples including 156 primary tumours,
      along with the corresponding normal mucosa, and in five colon cancer cell lines,
      SW480, SW620, KM12C, KM12SM and KM12L4a. AEG-1 protein expression was
      investigated by immunohistochemistry in paraffin-embedded materials from 74
      distant normal mucosa, 107 adjacent mucosa, 158 primary tumour, 35 lymph node
      metastasis and 9 liver metastasis samples. In addition, the AEG-1 protein
      expression was elucidated in the cell lines by Western blot. RESULTS: The lymph
      node metastatic cell line SW620 had a significantly higher AEG-1 mRNA (0.27 +/-
      0.02) expression compared to the primary tumour cell line SW480 (0.17 +/- 0.04, p
      = 0.026). AEG-1 expression at the mRNA level and/or the protein level was
      significantly up-regulated gradually from normal mucosa to primary CRC, and then
      to lymph node metastasis and finally to liver metastasis (p < 0.05). There were
      significant associations of AEG-1 mRNA expression with tumour location (p =
      0.047), as well as mRNA and protein expression with the tumour stage (p < 0.03).
      Furthermore AEG-1 protein expression was positively related to biological
      variables including NF-kappaB, p73, Rad50 and apoptosis (p < 0.05). CONCLUSION:
      AEG-1 is up-regulated, at the mRNA and the protein level, during CRC development
      and aggressiveness, and is related to tumour location and stage. It may play its
      role in CRC through the NF-kappaB signaling pathway.

PMID- 22643065
TI  - Visual acuity and contrast sensitivity of adult zebrafish.
AB  - BACKGROUND: The aim of this study was to evaluate the visual acuity of adult
      zebrafish by assessing the optokinetic reflex. Using a modified commercially
      available optomotor device (OptoMotry(r)), virtual three-dimensional gratings of
      variable spatial frequency or contrast were presented to adult zebrafish. In a
      first experiment, visual acuity was evaluated by changing the spatial frequency
      at different angular velocities. Thereafter, contrast sensitivity was evaluated
      by changing the contrast level at different spatial frequencies. RESULTS: At the
      different tested angular velocities (10, 15, 20, 25, and 30 d/s) and a contrast
      of 100%, visual acuity values ranged from 0.56 to 0.58 c/d. Contrast sensitivity
      measured at different spatial frequencies (0.011, 0.025, 0.5, 0.1, 0.2, 0.3, 0.4,
      0.5 and 0.55 c/d) with an angular velocity of 10 d/s and 25 d/s revealed an
      inverted U-shaped contrast sensitivity curve. The highest mean contrast
      sensitivity (+/-SD) values of 20.49 +/- 4.13 and 25.24 +/- 8.89 were found for a
      spatial frequency of 0.05 c/d (angular velocity 10 d/s) and 0.1 c/d (angular
      velocity 25 d/s), respectively. CONCLUSIONS: Visual acuity and contrast
      sensitivity measurements in adult zebrafish with the OptoMotry(r) device are
      feasible and reveal a remarkably higher VA compared to larval zebrafish and mice.

PMID- 22643066
TI  - EGFR status and EGFR ligand expression influence the treatment response of head
      and neck cancer cell lines.
AB  - BACKGROUND: Combination treatment (chemoradiotherapy) is the standard treatment
      for locally advanced head and neck squamous cell carcinoma (HNSCC); however,
      treatment resistance and local recurrence are significant problems. A high level
      of epidermal growth factor receptor (EGFR) has been associated with a more
      aggressive phenotype as well as decreased responsiveness to radio- or
      chemotherapy. We examined the role of EGFR status and EGFR ligand expression for
      the treatment response. METHODS: Intrinsic sensitivity to radiotherapy,
      cisplatin, and cetuximab treatments was investigated in 25 HNSCC cell lines. EGFR
      gene copy number, mRNA and protein expression, EGFR and Akt phosphorylation
      status, and mRNA expression of the EGFR ligands were analyzed using quantitative
      PCR and ELISA and assessed for their impact on treatment sensitivity. RESULTS:
      Different treatment modalities yielded great diversity in outcome; of note,
      cetuximab treatment stimulated growth in one cell line. When treatments were
      combined primarily additive effects were observed. While radioresistance tended
      to be associated with a high level of phosphorylated EGFR (pEGFR; P = 0.09),
      cetuximab-resistant cells had low levels of pEGFR (P = 0.13). The three most
      cetuximab-sensitive cell lines had high EGFR gene copy numbers. Furthermore,
      cetuximab treatment response was significantly correlated with epiregulin mRNA
      expression (r = -0.408, P = 0.043). Cisplatin-resistant tumor cells expressed
      significantly lower levels of EGFR protein (P = 0.04) compared to cisplatin
      sensitive cells and tended to have lower levels of phosphorylated Akt (pAkt; P =
      0.13) and lower expression levels of amphiregulin (P = 0.18). CONCLUSIONS:
      Epidermal growth factor receptor status and ligand expression influence the
      treatment sensitivity of HNSCC cells and may be useful as predictive markers.

PMID- 22643067
TI  - Explorative study on patient's perceived knowledge level, expectations,
      preferences and fear of side effects for treatment for allergic rhinitis.
AB  - BACKGROUND: In spite of the high prevalence of allergic rhinitis (AR) and the
      evidence-based guidelines for treatment, little is known about the patients'
      perceived knowledge level, expectations, preferences for treatment, and fear for
      side effects of treatment for AR. This study aimed at gaining insight into these
      patient-related factors. METHODS: This explorative cross-sectional survey study
      included a convenience sample of 170 patients with rhinitis and clinical
      suspicion of allergy at the department of Otorhinolaryngology and Allergology.
      Patients' perceived knowledge level, expectations, patient preferences, and fear
      of side effects of allergy treatment were collected via a self-report
      questionnaire developed for the purpose of this study. RESULTS: 22% of all
      patients (38/170) reported to have knowledge about anti-allergic treatment. 40%
      (55/170) of rhinitis patients expected to be cured by the prescribed treatment,
      whereas 43% (73/170) of patients expected suppression of allergic symptoms. Nasal
      spray was the preferred route of anti-allergic drug administration in 30%
      (52/170) of patients, followed by oral treatment (24%; 42/170), combination
      therapy (16%; 30/170), and injection therapy (15%; 27/170). More patients would
      choose a combination treatment with step-down approach (31%; 53/170) than mono
      therapy with a step-up approach (20%; 34/170). Fear for side effects was reported
      mainly for nasal corticosteroids (48%; 81/170) and less for oral antihistamines
      (33%; 36/170), leucotriene antagonists (21%, 36/170) and immunotherapy (19%,
      33/170). CONCLUSIONS: Patients consulting for rhinitis have high expectations of
      anti-allergic treatment, prefer a nasal spray above oral treatment, prefer
      combined treatment rather than monotherapy, and fear adverse events of anti
      allergic treatment.

PMID- 22643068
TI  - Recognition of and intervention in forced marriage as a form of violence and
      abuse.
AB  - This paper highlights the importance of recognising forced marriage as a form of
      violence and draws attention to the interventions that are developing in Europe
      as a response to forced marriage. The paper highlights the difficulties of
      conflating all child marriages as forced marriage and discusses the different
      contexts of childhood in different parts of the globe. The UK is reputed to have
      the widest range of policy interventions and practice guidance to tackle forced
      marriage and is therefore used as a case study in this paper, but reference is
      also made to other countries thus ensuring a wider relevance. The paper's
      analysis of UK based research studies on forced marriage identifies three key
      themes: i) lack of adequate reporting of incidents of forced marriage; ii) lack
      of professional knowledge of forced marriage and their fear of intervention; iii)
      the tension between conceptualizing forced marriage as purely cultural or as a
      form of gender based violence. It also highlights the largely legislative
      responses to forced marriage in Europe; Civil Protection for victims of forced
      marriage in the UK is discussed and a critical analysis is offered of the
      increase in marriage and sponsorship age in the UK and in many European
      countries. Health and clinical issues related to forced marriage are highlighted
      and the paper calls for further research globally to i) better understand the
      extent and nature of forced marriage; ii) to evaluate current interventions; iii)
      to investigate the clinical and potential mental health implications of forced
      marriage.

PMID- 22643069
TI  - Public justification of intimate partner violence: a review of the literature.
AB  - Understanding the extent to which the general public justifies intimate partner
      violence (IPV) is necessarily to explain perpetration, victimization, and
      response to this behavior. This article provides a literature review of
      quantitative studies measuring IPV justification among the general population.
      Key word searching of two databases plus bibliographies, and the web yielded 23
      studies that provided comparable measures of IPV justification. Results are
      summarized for the prevalence of IPV justification identified for each country
      including differences in justification based on the initiating event (e.g.,
      burning food and infidelity), sociodemographic differences in justification and
      differences across countries. No study identified a zero prevalence of IPV
      justification and percentages varied considerably across and within countries.
      Females tended to report a higher rate of IPV justification than males and
      younger respondents tended to report a higher rate IPV justification than their
      older counterparts. Further research is needed to understand IPV justification
      within and across nations as well as to explore the impact this has on IPV
      prevalence and policy.

PMID- 22643070
TI  - FXR agonist GW4064 increases plasma glucocorticoid levels in C57BL/6 mice.
AB  - Since high expression of farnesoid X receptor (FXR) has been detected in
      glucocorticoid-producing adrenocortical cells, we evaluated the potential role of
      FXR in adrenal glucocorticoid production. FXR agonist GW4064 increased fasting
      plasma corticosterone levels (+45%; P<0.01) in C57BL/6 mice, indicative of
      enhanced adrenal steroidogenesis. GW4064 treatment did not affect plasma ACTH
      levels, adrenal weight, or adrenal expression of steroidogenic genes. Scavenger
      receptor BI (SR-BI) mRNA and protein expression, respectively, increased 1.9-fold
      (P<0.01) and 1.5-fold, which suggests a stimulated lipoprotein-associated
      cholesterol uptake into the adrenals upon GW4064 treatment. In line with an
      enhanced flux of cellular cholesterol into the steroidogenic pathway, adrenal
      unesterified and esterified cholesterol stores were 21-41% decreased (P<0.01)
      upon GW4064 treatment. In conclusion, we have shown that the FXR agonist GW4064
      stimulates plasma corticosterone levels in C57BL/6 mice. Our findings suggest a
      novel role for FXR in the modulation of adrenal cholesterol metabolism and
      glucocorticoid synthesis in mice.

PMID- 22643071
TI  - Immune responses induced by DNA vaccines bearing Spike gene of PEDV combined with
      porcine IL-18.
AB  - Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic
      diarrhea, a highly contagious enteric disease of swine. The Spike (S) protein is
      one of the main structural proteins of PEDV capable of inducing neutralizing
      antibodies in vivo. Herein, we generated three distinct DNA constructs in the
      eukaryotic expression plasmid pVAX1; one encoding the S protein [pVAX1-(PEDV-S)],
      the second encoding the N-terminal fragment (S1) [pVAX1-(PEDV-S1)] containing
      potent antigenic sites, and the third expressing the porcine interleukin-18 (pIL
      18) [pVAX1-(IL-18)]. Immunofluorescence assays in BHK-21 cells demonstrated
      successful protein expression from all 3 constructs. Kunming mice were injected
      separately with each of these constructs or with a pVAX1-(PEDV-S1)/pVAX1-(IL-18)
      combination, an attenuated PEDV vaccine, or vector only control. Animals were
      examined for T lymphocyte proliferation, anti-PEDV antibodies, IFN-gamma and IL-4
      protein levels, and cytotoxic T cell function in mouse peripheral blood and
      spleen. In all cases, results showed that pVAX1-(PEDV-S) and the combination of
      pVAX1-(PEDV-S1) with pVAX1-(IL-18) induced the strongest responses; however, pIL
      18 had no adjuvant effects when given in combination with pVAX1-(PEDV-S1).

PMID- 22643073
TI  - Snake venomics of two poorly known Hydrophiinae: Comparative proteomics of the
      venoms of terrestrial Toxicocalamus longissimus and marine Hydrophis
      cyanocinctus.
AB  - The venom proteomes of Toxicocalamus longissimus and Hydrophis cyanocinctus, a
      fossorial and a marine species, respectively, of the Hydrophiinae genus of
      Elapidae, were investigated by Edman degradation of RP-HPLC isolated proteins,
      and de novo MS/MS sequencing of in-gel derived tryptic peptide ions. The toxin
      arsenal of T. longissimus is made up of 1-2 type-I PLA(2) molecules, which
      account for 6.5% of the venom proteins, a minor PIII-SVMP (1.4% of the venom
      toxins), and ~20 members of the 3FTx family comprising 92% of the venom proteome.
      Seventeen proteins (5 type-I PLA(2)s and 12 3FTxs) were found in the venom of H.
      cyanocinctus. Three-finger toxins and type-I PLA(2) proteins comprise,
      respectively, 81% and 19% of its venom proteome. The simplicity of the H.
      cyanocinctus venom proteome is highlighted by the fact that only 6 venom
      components (3 short-chain neurotoxins, two long-chain neurotoxins, and one PLA(2)
      molecule) exhibit relative abundances >5%. As expected from its high neurotoxin
      abundance, the LD(50) for mice of H. cyanocinctus venom was fairly low,
      0.132MUg/g (intravenous) and 0.172MUg/g (intraperitoneal). Our data indicate that
      specialization towards a lethal cocktail of 3FTx and type-I PLA(2) molecules may
      represent a widely adopted trophic solution throughout the evolution of Elapidae.
      Our results also points to a minimization of the molecular diversity of the toxin
      arsenal of the marine snake Hydrophis cyanocinctus in comparison to the venom
      proteome of its terrestrial relatives, and highlight that the same evolutionary
      solution, economy of the toxin arsenal, has been convergently adopted by
      different taxa in response to opposite selective pressures, loss and gain of
      neurotoxicity.

PMID- 22643072
TI  - Plasmodium vivax Duffy binding protein: baseline antibody responses and parasite
      polymorphisms in a well-consolidated settlement of the Amazon Region.
AB  - OBJECTIVE: To investigate risk factors associated with the acquisition of
      antibodies against Plasmodium vivax Duffy binding protein (PvDBP) - a leading
      malaria vaccine candidate - in a well-consolidated agricultural settlement of the
      Brazilian Amazon Region and to determine the sequence diversity of the PvDBP
      ligand domain (DBP(II)) within the local malaria parasite population. METHODS:
      Demographic, epidemiological and clinical data were collected from 541 volunteers
      using a structured questionnaire. Malaria parasites were detected by conventional
      microscopy and PCR, and blood collection was used for antibody assays and
      molecular characterisation of DBP(II). RESULTS: The frequency of malaria
      infection was 7% (6% for P. vivax and 1% for P. falciparum), with malaria cases
      clustered near mosquito breeding sites. Nearly 50% of settlers had anti-PvDBP IgG
      antibodies, as detected by enzyme-linked immunosorbent assay (ELISA) with
      subject's age being the only strong predictor of seropositivity to PvDBP.
      Unexpectedly, low levels of DBP(II) diversity were found within the local malaria
      parasites, suggesting the existence of low gene flow between P. vivax
      populations, probably due to the relative isolation of the studied settlement.
      CONCLUSION: The recognition of PvDBP by a significant proportion of the
      community, associated with low levels of DBP(II) diversity among local P. vivax,
      reinforces the variety of malaria transmission patterns in communities from
      frontier settlements. Such studies should provide baseline information for
      antimalarial vaccines now in development.

PMID- 22643074
TI  - Furthering our understanding of stroke and other neurological pathologies.

PMID- 22643076
TI  - Neuroprotection targeting ischemic penumbra and beyond for the treatment of
      ischemic stroke.
AB  - Neuroprotection to attenuate or block the ischemic cascade and salvage neuronal
      damage has been extensively explored for the treatment of ischemic stroke. In the
      last two decades, neuroprotective strategy has been evolving from targeting a
      signal pathway in neurons to protecting all  neurovascular components and
      improving cell-cell and cell-extracellular matrix interaction that ultimately
      benefits the brain recovery after ischemic stroke. The progression from
      potentially reversible to irreversible injury in the ischemic penumbra has
      provided the opportunity  to develop therapies to attenuate the ischemic stroke
      damage. Thus, the ischemic penumbra has been the main target for the current
      neuroprotective intervention. However, despite our increasing knowledge of the
      physiologic, mechanistic, and imaging characterizations of the ischemic penumbra,
      no effective neuroprotective therapy has been found so far for the treatment of
      ischemic stroke. The current acute neuroprotective approach focusing on the
      damaging mechanisms at the ischemic penumbra is greatly limited by the rapid
      evolution of the deleterious cascades in the ischemic penumbra.  Neuroprotective
      intervention attempts to promote endogenous repairing in the transition zone of
      the penumbra for the therapeutic purposes may overcome the unrealistic
      therapeutic windows under the current neuroprotective strategy. In addition,
      increasing evidence has indicated ischemic stroke  could induce long-lasing
      cellular and hemodynamic changes beyond the ischemic territory. It is unclear
      whether and how the global responses induced by the ischemic cascade contribute
      to the progression of cognitive impairment after ischemic stroke. The prolonged
      pathophysiological cascades  induced by ischemic stroke beyond the ischemic
      penumbra might provide novel therapeutic opportunities for the neuroprotective
      intervention, which could prevent or slow down the progression of vascular
      dementia after ischemic stroke.

PMID- 22643075
TI  - Injury and repair in the neurovascular unit.
AB  - The neurovascular unit provides a conceptual framework for investigating the
      pathophysiology of how brain cells die after stroke, brain injury, and
      neurodegeneration. Emerging data now suggest that this concept can be further
      extended. Cell-cell signaling between neuronal, glial,  and vascular elements in
      the brain not only mediates the mechanisms of acute injury, but integrated
      responses in these same elements may also be required for recovery as the entire
      neurovascular unit attempts to reorganize and remodel. Understanding the common
      signals and substrates of this  transition between acute injury and delayed
      repair in the neurovascular unit may reveal useful paradigms for augmenting
      neuronal, glial, and vascular plasticity in damaged and diseased brain.

PMID- 22643078
TI  - Ozagrel for acute ischemic stroke: a meta-analysis of data from randomized
      controlled trials.
AB  - BACKGROUND: In patients with acute ischemic stroke (AIS), platelets are activated
      in the acute phase, releasing neurotoxic, and thrombogenic eicosanoids, which may
      reduce the brain blood flow and cause brain damage. Sodium ozagrel (ozagrel), a
      thromboxane A2 synthase inhibitor,  is one of the most studied drugs which may
      reduce the risk of neurological impairment and reduce the volume of brain damage.
      We systematically reviewed all published randomized controlled trials (RCTs)
      comparing ozagrel with control among patients with AIS. METHODS: We searched
      seven  databases, using the Cochrane Stroke Group search strategy and the terms
      of ozagrel and stroke. Two independent investigators evaluated trial quality
      using the Cochrane Collaboration's risk of bias tool and extracted the data from
      each study. Pooled analyses for the outcomes of combined  death or disability and
      improvement of neurological impairment were calculated. RESULTS: The effect of
      ozagrel on the reduction of death for AIS at the end of follow-up was relative
      risk (RR) = 0.67 (95% CI: 0.11 to 4.04, P = 0.67).  The effect evaluated by
      Modified Edinburgh-Scandinavian Stroke Scale (MESSS) at the end of treatment was
      mean difference (MD) = -4.17 (95% CI, -4.95 to -3.40; P<0.00001). The most severe
      adverse events of ozagrel were digestive  hemorrhage and hemorrhagic stroke;
      however, there was no significant difference between the two groups. The subgroup
      analysis of different dose showed that 80 and 160 mg ozagrel per day might both
      increase the improvement of the neurological impairment. DISCUSSION: During
      scheduled  treatment, ozagrel is effective for the improvement of neurological
      impairment for AIS patients. However, the evidence of ozagrel to reduce the long
      term death or disability is limited and quality of these trials is insufficent
      hence, large-sample and high quality RCTs are warrented to confirm  the efficacy
      of ozagrel for acute ischemic stroke.

PMID- 22643077
TI  - NADPH oxidase in stroke and cerebrovascular disease.
AB  - Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) was originally
      identified in immune cells as playing an important microbicidal role. In stroke
      and cerebrovascular disease, inflammation is increasingly being recognized as
      contributing negatively to neurological outcome,  with NOX as an important source
      of superoxide. Several labs have now shown that blocking or deleting NOX in the
      experimental stroke models protects from brain ischemia. Recent work has
      implicated glucose as an important NOX substrate leading to reperfusion injury,
      and that NOX inhibition can  improve the detrimental effects of hyperglycemia on
      stroke. NOX inhibition also appears to ameliorate complications of thrombolytic
      therapy by reducing blood-brain barrier disruption, edema formation, and
      hemorrhage. Further, NOX from circulating inflammatory cells seems to contribute 
      more to ischemic injury more than NOX generated from endogenous brain residential
      cells. Several pharmacological inhibitors of NOX are now available. Thus,
      blocking NOX activation may prove to be a promising treatment for stroke as well
      as an adjunctive agent to prevent its secondary complications.

PMID- 22643079
TI  - Frequency and etiological diagnosis of ischemic stroke in Chinese young adults.
AB  - Cerebrovascular disease is the second commonest cause of death, and over a third
      of stroke deaths occur in developing countries. To fulfil the current gap on
      data, this systematic review is focused on the epidemiology of stroke, stroke
      subtypes, risk factors, etiological diagnosis,  the status of treatment and
      mortality of young adults' ischemic stroke in China.

PMID- 22643080
TI  - The relationship of asymptomatic intracranial artery stenosis and Framingham
      stroke risk profile in a Northern Chinese industrial city.
AB  - BACKGROUND: Intracranial artery stenosis may be the most frequent cause of
      ischemic stroke in the world. Early detection of asymptomatic intracranial artery
      stenosis may allow for therapeutic intervention. Most elements of the Framingham
      stroke risk profile (FSRP) are also risk  factors for intracranial artery
      stenosis. Thus, the FSRP might play a role in detecting asymptomatic intracranial
      artery stenosis. OBJECTIVE: To investigate the relationship between the FSRP and
      asymptomatic intracranial artery stenosis. METHODS: A sample of 5852 subjects 
      (age >40 years) was selected from the KaiLuan study. All participants received
      transcranial Doppler ultrasound examinations to detect the presence and quantify
      the severity of intracranial arterial stenosis. Demographic and clinical
      variables were investigated at the time of examination.  Binary logistic
      regression analyses was performed to determine the odds ratio of FSRP components
      to asymptomatic intracranial stenosis before and after adjusted for gender, body
      mass index (BMI), and total cholesterol (TC). RESULTS: The subjects with
      intracranial artery stenosis  were older than those without (68.2 versus 64.9),
      and the systolic blood pressure was higher in those with intracranial artery
      stenosis (146.86 versus 136.39). Among intracranial artery stenosis subjects,
      77.5% had hypertension, 26.1% had diabetes,  8.9% had left ventricular
      hypertrophy, and 4.8% had atrial fibrillation. Logistic regression analyses
      revealed that age, systolic blood pressure, diabetes, atrial fibrillation, and
      left ventricular hypertrophy were risk factors for intracranial artery stenosis.
      The incidence  of asymptomatic intracranial artery stenosis correlated with
      increasing FSRP scores. The odds ratios of intracranial artery stenosis from the
      lowest to the highest FSRP quartiles were as follows: 1 (reference group), 1.77
      (95% CI: 1.23-2.56), 2.84 (95% CI:  2.02-3.98), 5.65 (95% CI: 4.03-7.93).
      CONCLUSION: FSRP plays an important role in detecting asymptomatic intracranial
      artery stenosis.

PMID- 22643081
TI  - Association of plaque compositions and stenosis patterns in carotid bifurcation
      using MR imaging.
AB  - OBJECTIVES: To investigate the relationship between plaque compositions and
      stenosis patterns in patients with atherosclerotic plaques at the carotid
      bifurcation using magnetic resonance (MR) imaging. METHODS: One hundred and four
      carotid arteries with stenosis over  50% from 75 symptomatic stroke patients (64
      male and 11 female; mean age 58.2+/-13.3 years) were studied. Plaque compositions
      were analyzed by high-resolution MR imaging using a 3.0T MR with a surface coil.
      Stenosis patterns were classified into three types according  to contrast
      enhanced MR angiography images. Correlations of different components of plaques
      and stenosis patterns were analyzed. RESULTS: One hundred and four carotid
      arteries were analyzed. Three stenosis patterns were identified. The prevalences
      of the three patterns are as follows:  type I (total occlusion) at 27.9%
      (29/104), type II (local plaque with normal distant flow) at 56.7% (59/104), and
      type III (local plaque with impaired distant flow) at 15.4% (16/104). The
      contingency coefficients between stenosis pattern and stability, intraplaque
      hemorrhage  (IPH), lipid necrotic core (LNC), and ulcer were 0.383 (P = 0.000),
      0.290 (P = 0.008), 0.439 (P = 0.000), and 0.388 (P = 0.000), respectively.
      Multinomial analysis showed  that compared with type III vessels, type I vessels
      were more likely to contain IPH (P = 0.019) and less likely to contain large LNC
      (P = 0.001); type II vessels had a greater possibility for containing IPH than
      type III vessels (P = 0.009);  LNC was more likely to be found in type II than in
      type I vessels (P = 0.000). No significant difference was found in ulceration
      prevalence between type II and type III vessels (P = 0.058). CONCLUSIONS: The
      current study demonstrated  positive associations between stenosis patterns and
      plaque compositions.

PMID- 22643082
TI  - Ethanol reduces expression of apoptotic proteins after hypoxia/reoxygenation in a
      brain slice model.
AB  - OBJECTIVES: Acute administration of ethanol is associated with neuroprotection in
      rat with transient cerebral ischemia. To investigate the molecular mechanism of
      ethanol-induced neuroprotection, we determined the effect of ethanol on
      expression levels of apoptotic proteins, including  caspase-3, Bcl-2-associated X
      protein (Bax), and apoptosis-inducing factor (AIF). To assess overall cell
      viability following ethanol treatment, ADP/ATP ratio was measured. METHODS: Brain
      slice cultures were prepared using postnatal 10-day-old Sprage-Dawley rats. Brain
      slices  were divided into control and hypoxia groups. Hypoxia groups include a
      non-treatment group and three treatment groups (10, 30, or 90 mM ethanol). Levels
      of caspase-3, Bax, and AIF were determined by western blot. ADP/ATP ratio was
      assessed using ADP/ATP assay kit. RESULTS: Ethanol  administration reduced
      ADP/ATP ratio in all three treatment groups (10, 30, and 90 mM). A reduction in
      caspase-3, BAX, and AIF expression was observed with all three treatment groups
      in conjunction with decreased ADP/ATP levels. The three treatment groups showed
      similar levels of reduction  in ADP/ATP ratio and apoptotic protein expression.
      DISCUSSION: Ethanol-induced neuroprotection involves inhibition of apoptotic
      pathways, including Bax, caspase-3, and AIF. Dose range of 10-90 mM ethanol
      provides similar level of protection compared to 10 mM ethanol.

PMID- 22643083
TI  - Toll-like receptor 4 signaling is involved in PACAP-induced neuroprotection in
      BV2 microglial cells under OGD/reoxygenation.
AB  - OBJECT: The neuroprotective effects of pituitary adenylate cyclise-activating
      polypeptide (PACAP) have been well documented in vivo and in vitro. However, the
      mechanisms by which PACAP protected microglia from ischemic/hypoxic injury via
      inhibition of microglia activation remain unclear. Toll-like receptor 4 (TLR4)
      plays a considerable role in the induction of innate immune and inflammatory
      responses. The purpose of this study is to investigate the effect of PACAP on the
      oxygen and glucose deprivation (OGD)/reoxygenation BV2 microglia and to explore
      the role of TLR4/myeloid differentiation protein 88 (MyD88)/nuclear factor-kappa
      B (NF-kappaB) pathway in the neuroprotective effects of PACAP. METHODS: We
      conducted OGD/reoxygenation by placing BV2 microglia into an airtight chamber and
      in glucose-free medium. BV2 microglia cell viability was determined by MTT [3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay. Western blot
      was utilized to detect TLR4, MyD88 expression, inhibitory protein of NF-kappaB
      (IkappaB) phosphorylation/degradation, NF-kappaB activation. Level of tumor
      necrosis factor-alpha (TNF-alpha) in culture medium was measured with enzyme
      linked immunosorbent assay (ELISA). Apoptosis was determined by flow cytometry.
      RESULTS: We found that pretreatment with PACAP to BV2 cells immediately before
      OGD/reoxygenation significantly alleviated microglia hypoxic injury. PACAP
      inhibited upregulation of TLR4, MyD88 and NF-kappaB in BV2 microglial cells
      exposed to OGD/reoxygenation. PACAP administration also significantly reduced the
      production of proinflammatory cytokines and apoptosis in BV2 microglia exposed to
      OGD/reoxygenation. DISCUSSION: Pretreatment with PACAP inhibited activation of
      the TLR4/MyD88/NF-kappaB signaling pathway and decreased inflammatory cytokine
      levels, as well as apoptosis in microglia, thereby attenuating microglia hypoxic
      injury. Our results suggested that TLR4-mediated MyD88-dependent signaling
      pathway contributed to neuroprotection of PACAP to microglia against
      OGD/reoxygenation.

PMID- 22643084
TI  - Wnt signaling pathway is involved in the pathogenesis of amyotrophic lateral
      sclerosis in adult transgenic mice.
AB  - OBJECTIVE: Our aim was to examine the change in expression of molecules involved
      in Wnt signaling in the pathogenesis of amyotrophic lateral sclerosis (ALS) in
      adult transgenic mice, and to reveal the relationship between the Wnt signaling
      pathway and the pathogenesis of ALS. METHODS: We determined the expression of
      Wnt2, Wnt7a, and GSK-3beta in the spinal cord of SOD1(G93A) ALS transgenic mice
      at different ages using reverse transcriptase-polymerase chain reaction, western
      blot, and immunohistochemistry. Using double labeling, we determined whether
      Wnt2, Wnt7a,  and GSK-3beta were colocalized with beta-tubulin III, for neurons,
      or glial fibrillary acidic protein, for mature astrocytes. RESULTS: Wnt2, Wnt7a
      mRNA and protein in the spinal cord of ALS mice were upregulated and compared
      with wild-type mice. Phospho-GSK-3beta (Ser 9) protein  levels in the spinal cord
      of ALS mice were upregulated. Moreover, the immunoreactivity of Wnt2, Wnt7a, and
      phospho-GSK-3beta (Ser 9) was strong in ALS mice but weak in wild-type mice at
      the same time points. Double immunofluorescence labeling showed that Wnt2 and
      Wnt7a were expressed in both  neurons and astrocytes, whereas GSK-3beta was
      expressed only in neurons. Most of the double positive cells were located in the
      ventral horns of the gray matter, the locus of neurodegeneration. DISCUSSION:
      Neurodegeneration upregulated the expression of Wnt2 and Wnt7a in the spinal 
      cord of ALS mice, which in turn activated Wnt signaling, and accordingly
      inhibited GSK-3beta activity in disease progression of ALS in adult transgenic
      mice; this could regulate the downstream gene of the Wnt signaling pathway and
      promote cell proliferation.

PMID- 22643085
TI  - Activation of Akt/GSK-3beta/beta-catenin signaling pathway is involved in
      survival of neurons after traumatic brain injury in rats.
AB  - OBJECTIVE: Apoptotic cell death is an important factor influencing the prognosis
      after traumatic brain injury (TBI). Akt/GSK-3beta/beta-catenin signaling plays a
      critical role in the apoptosis of neurons in several models of neurodegeneration.
      The goal of this study was to determine  if the mechanism of cell survival
      mediated by the Akt/GSK-3beta/beta-catenin pathway is involved in a rat model of
      TBI. METHODS: TBI was performed by a controlled cortical impact device.
      Expression of Akt, phospho-Akt, GSK-3beta, phospho-GSK-3beta, beta-catenin,
      phospho-beta-catenin  were examined by immunohistochemistry and Western blot
      analysis. Double immunofluorenscent staining was used to observe the neuronal
      expression of the aforementioned subtrates. Terminal deoxynucleotidyl transferase
      mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) staining  was
      performed to identify apoptosis. RESULTS: Western blot analysis showed that
      phospho-Akt significantly increased at 4 hours post-TBI, but decreased after 72
      hours post-TBI. Phospho-GSK-3beta - phosphorylated by phospho-Akt - slightly
      increased at 4 hours post-TBI  and peaked at 72 hours post-TBI. These changes in
      Phospho-GSK-3beta expression were accompanied by a marked increase in expression
      of phospho-beta-catenin at 4 hours post-TBI which was sustained until 7 days post
      TBI. Double staining of phospho-Akt and NeuN revealed the colocalization of
      phospho-Akt  positive cells and neuronal cells. In addition, double staining of
      phospho-Akt and TUNEL showed no colocalization of phospho-Akt cells and TUNEL
      positive cells. CONCLUSION: Phosphorylation of Akt (Ser473) and GSK3beta (Ser9)
      was accelerated in the injured cortex, and involved in  the neuronal survival
      after TBI. Moreover, neuroprotection of beta-catenin against ischemia was partly
      mediated by enhanced and persistent activation of the Akt/GSK3beta signaling
      pathway.

PMID- 22643086
TI  - Changes in spinal cord met-enkephalin levels and mechanical threshold values of
      pain after pulsed radio frequency in a spared nerve injury rat model.
AB  - OBJECTIVES: The present study investigated changes in the met-enkephalin (M-ENK)
      levels in the spinal cord. We also determined the mechanical threshold value of
      pain in spared nerve injury (SNI) rats after applying pulsed radiofrequency (PRF)
      on L5 dorsal root ganglion (DRG). METHODS: Sixty-four rats were divided into four
      groups: the normal group (n = 16), the control group (n = 16), the sham
      intervention group (n = 16), and the PRF group (n = 16). With exception for the
      normal group, the other three groups  were treated with an established SNI model.
      After 7 days, PRF or sham intervention was applied on the right L5 DRG. The M-ENK
      levels in the spinal cord were examined by radioimmunoassay 24 hours after
      applying PRF or sham operation. Mechanical threshold values of pain were also
      tested 1 day  before SNI procedure, 1 and 2 days after SNI procedure, and 2 and
      24 hours after applying PRF or sham operation. RESULTS: Twenty-four hours after
      treatment with PRF, M-ENK levels in spinal cord increased significantly, while no
      changes were detected in the sham intervention group.  Hyperalgesia was found in
      rats 1-2 days after SNI procedure and was improved by PRF. This was demonstrated
      by an increased mechanical threshold of pain 2 and 24 hours after the PRF. The
      sham intervention group showed no change in the mechanical threshold of pain.
      CONCLUSION: This study demonstrates that applying PRF on the DRG can improve
      hyperalgesia and increase M-ENK levels in the spinal cord of SNI rats within 24
      hours. These findings indicate that the endogenous M-ENK in the spinal cord is
      involved in the mechanism of PRF on the therapy of neuropathic pain.

PMID- 22643087
TI  - Correlates of weight gain during long-term risperidone treatment in children and
      adolescents.
AB  - BACKGROUND: Most clinical trials of antipsychotics in children are brief, failing
      to address their long-term safety, particularly when taken concurrently with
      other psychotropics. This hypothesis-generating analysis evaluates potential
      correlates of weight gain in children receiving extended risperidone treatment.
      METHODS: Medically healthy 7-17 year-old patients treated with risperidone for
      six months or more were enrolled. Anthropometric measurements were conducted.
      Developmental and medication history was obtained from the medical record.
      Information related to birth weight, dietary intake, physical activity, and
      parental weight was collected. Mixed regression analyses explored the
      contribution of various demographic and clinical factors to age- and sex-adjusted
      weight and body mass index (BMI) z scores over the treatment period. RESULTS: The
      sample consisted of 110 patients (89% males) with a mean age of 11.8 years (sd =
      2.9) upon enrollment. The majority had an externalizing disorder and received
      0.03 mg/kg/day (sd = 0.02) of risperidone, for 2.5 years (sd = 1.7), to primarily
      target irritability and aggression (81%). Polypharmacy was common with 71%
      receiving psychostimulants, 50% selective serotonin reuptake inhibitors (SSRIs),
      and 32% alpha2-agonists. Weight and BMI z score were positively correlated with
      baseline weight at the start of risperidone, treatment duration, and the weight
      adjusted dose of risperidone but inversely associated with the weight-adjusted
      dose of psychostimulants and the concurrent use of SSRIs and alpha2-agonists. The
      effect of risperidone dose appeared to attenuate as treatment extended while that
      of psychostimulants became more significant. The rate of change in weight (or
      BMI) z score prior to and within the first 12 weeks of risperidone treatment did
      not independently predict future changes neither did birth weight, postnatal
      growth, dietary intake, physical activity, or parental weight. CONCLUSIONS: This
      comprehensive analysis exploring correlates of long-term weight (or BMI) change
      in risperidone-treated youths revealed that pharmacotherapy exerts significant
      but complex effects. TRIAL REGISTRATION: Not applicable.

PMID- 22643097
TI  - Implicit contextual learning in prodromal and early stage Huntington's disease
      patients.
AB  - Huntington's disease (HD) is a genetic neurodegenerative disorder affecting the
      basal ganglia. These subcortical structures are particularly important for motor
      functions, response selection and implicit learning. In the current study, we
      have assessed prodromal and symptomatic HD participants with an implicit
      contextual learning task that is not based on motor learning, but on a purely
      visual implicit learning mechanism. We used an implicit contextual learning task
      in which subjects need to locate a target among several distractors. In half of
      the trials, the positions of the distractors and target stimuli were repeated. By
      memorizing this contextual information, attention can be guided faster to the
      target stimulus. Nine symptomatic HD participants, 16 prodromal HD participants
      and 22 control subjects were included. We found that the responses of the control
      subjects were faster for the repeated trials than for the new trials, indicating
      that their visual search was facilitated when repeated contextual information was
      present. In contrast, no difference in response times between the repeated and
      new trials was found for the symptomatic and prodromal HD participants. The
      results of the current study indicate that both prodromal and symptomatic HD
      participants are impaired on an implicit contextual learning task.

PMID- 22643098
TI  - Reduced cortical motor potentials underlie reductions in memory-guided reaching
      performance.
AB  - We used the event-related potential (ERP) methodology to examine differences in
      neural processing between visually and memory-guided reaches. Consistent with
      previous findings (e.g., Westwood, Heath, & Roy, 2003), memory-guided reaches
      undershot veridical target location to a greater extent than their visually
      guided counterparts. Analysis of the ERP data revealed that memory-guided reaches
      were associated with reduced potentials over medial-frontal cortex at target
      presentation and following movement onset. Further, we found that the amplitudes
      of the potentials over medial-frontal cortex for visually and memory-guided
      reaches were significantly correlated with the peak accelerations and
      decelerations of the reaching movements. Our results suggest that memory-guided
      reaches are mediated by a motor plan that is generated while a target is visible,
      and then stored in memory until needed--a result counter to recent behavioral
      theories asserting that memory-guided reaches are planned just before movement
      onset via a stored, sensory-based target representation.

PMID- 22643099
TI  - Race and ethnicity in clinical studies.

PMID- 22643100
TI  - Relationship of the temporofrontal rami of the facial nerve to the fascial layers
      of the temporal region.
AB  - BACKGROUND: Historically, dissection of the temporoparietal fascia immediately
      above the zygomatic arch has been avoided due to the risk of transection of the
      temporofrontal rami of the facial nerve. METHODS: A total of 8 fresh cadaveric
      hemi-faces have been dissected to investigate the relationship of the
      temporofrontal rami of the facial nerve to the fascial layers in the temporal
      region. RESULTS: The relationship of the temporofrontal rami of the facial nerve
      to the fascial layers in the temporal region is variable, with some deep rami
      coursing below the parotid-temporal fascia and other superficial rami reaching
      the temporoparietal fascia before entering the lateral edge of the orbicularis
      oculi. CONCLUSIONS: Dissection of the temporoparietal fascia immediately above
      the zygomatic arch may place superficial branches of the temporofrontal rami at
      risk.

PMID- 22643101
TI  - Bioengineered matrices--part 1: attaining structural success in biologic skin
      substitutes.
AB  - Skin defect closure after injury or disease may present significant
      reconstructive challenges. Traditional epidermal coverage alone in the form of
      skin grafts often fall short in providing stable cover to restore structure and
      function of the skin. Excessive wound contraction and scar formation,
      particularly in defects of dermis and epidermis, may create functional and
      aesthetic problems. Progress in our understanding of molecular biology and tissue
      engineering have produced major advances in skin substitute technology,
      particularly relating to the dynamic cellular/extracellular matrix interaction
      that is critical to successful incorporation of a skin substitute. However,
      currently available skin substitutes still exhibit a range of problems including
      excessive wound contraction and scar formation, poor host tissue incorporation,
      revascularization and, in some cases, structural deficiencies in matrix design.
      The design principles and structural composition of the matrix must take into
      account collagenous forms, inherent resistance, porosity, and hydration. The
      ultimate matrix should be one that promotes intrinsic regeneration by encouraging
      cellular incorporation and cellular/extracellular cross communication. Attention
      to basic structural details rather than reliance on specialized cellular or
      peptide additions to the mix may well produce the advances we seek in improved
      incorporation of bioengineered skin substitutes.

PMID- 22643102
TI  - Bioengineered matrices--part 2: focal adhesion, integrins, and the fibroblast
      effect.
AB  - Initial efforts at biologic skin replacement strategies were mainly directed
      toward keratinocyte regeneration and epithelial replacement. It soon became
      evident that without a good dermal scaffold, the long-term efficacy of epithelial
      replacement was very limited. Further studies have focused on matrix replacement
      predominantly involving collagen frameworks with or without cellular additions.
      The fibroblast is central to the process of dermal regeneration and to the
      success of biologic matrix design. The sequence of cellular focal adhesion,
      integrin phosphorylated activation, intracellular and extracellular signaling,
      cytoskeletal activation, changes in cell morphology, and cytokine growth factor
      interaction are all important in influencing cell proliferation, cell spreading,
      neocollagenesis, and collagen translocation. A basic acellular matrix with
      chemical composition and correct physical structure (pore size and resistance)
      that takes cognizance of this sequence of matrix deposition and fibroblast
      functionality should be successful in promoting intrinsic healing and dermal
      replacement.

PMID- 22643103
TI  - Common nerve decompressions of the upper extremity: reliable exposure using
      shorter incisions.
AB  - Considering that several different specialties perform nerve decompressions in
      the upper extremity, universal technical standards do not exist. Many of these
      procedures are performed via incisions that are made unnecessarily long to
      achieve adequate exposure of the nerves and their known anatomical compression
      points. The purpose of this article is to introduce reproducible techniques that
      reliably allow the necessary anatomical exposure while minimizing the length of
      required skin incisions. METHODS: The senior author's surgical approach to the
      most common nerve compression syndromes of the upper extremity is presented in
      detail. Typical incision lengths and surgical exposure are demonstrated
      photographically. The safety of using this technique is examined by review of the
      medical records of all patients undergoing this procedure from 2003 to 2011,
      looking for technical complications such as unintentional damage to nerves or
      adjacent structures. RESULTS: Three hundred twenty consecutive cases were
      identified in which the described techniques were used to release known
      anatomical compression points of the upper extremity nerves, including 161
      decompressions of the ulnar nerve at the elbow, 37 decompressions of the anterior
      interosseous nerve and 45 of the posterior interosseous nerve in the proximal
      forearm, and 77 decompressions of the radial sensory nerve in the distal forearm.
      Typical incision lengths we used for these procedures were 5 cm for the ulnar
      nerve, 4.5 cm for the anterior interosseous nerve, 4 cm for the posterior
      interosseous nerve, and 3 cm for the radial sensory nerve. Review of medical
      records revealed no incidences of unintentional injury to nerves or adjacent
      important structures. Functional and neurological recovery outcomes were not
      assessed, as those would be the subject of subsequent studies. CONCLUSIONS: Known
      anatomical compression points can be reliably accessed and decompressed for the
      treatment of all common upper extremity nerve compression syndromes using
      minimized skin incisions and the techniques presented in this article. With
      appropriate knowledge of anatomy, this can be performed without expensive
      equipment or any additional risk of injury to the patient, making classically
      described longer incisions unnecessarily morbid.

PMID- 22643104
TI  - Global contributions to Annals of Plastic Surgery: authorship in an English
      language journal by international colleagues.
AB  - We reviewed the contributor demographics of recent volumes of Annals of Plastic
      Surgery to quantify the contributions of authors from countries where the primary
      language is not English. For 2 volumes of Annals (63 and 65), such authors
      contributed 57% of the total articles published. Within the new section format of
      volume 66, authors from non-English language countries accounted for 60% of all
      original articles with substantial and often dominant representation in all
      sections. This survey shows that Annals publishes articles from an international
      population of contributors with effective inclusion of authors from countries
      with primary languages other than English.

PMID- 22643105
TI  - Factors influencing acute rejection of human hand allografts: a systematic
      review.
AB  - Acute rejection (AR) of human hand allografts (HHAs) may carry a risk of graft
      loss and leads to the need for immunosuppressive treatment. The literature on
      HHAs was reviewed to determine and evaluate the factors that trigger AR of HHAs.
      Clinical case reports of hand allograft transplantation published between 1999
      and 2011 in English, French, or German were reviewed systematically. The number
      of AR episodes was the main outcome measure. Sixty-eight episodes of AR were
      described in 28 recipients. Calcineurin inhibitor-based maintenance regimens were
      associated with significantly fewer AR episodes than non-calcineurin inhibitor
      based regimens (mean 1.9 vs 3.2; P = 0.018). In recipients who experienced
      cytomegalovirus infection, the mean number of episodes of AR was 4, whereas in
      those who did not experience cytomegalovirus infection it was 2.25 (P = 0.024).
      The planning of hand allograft transplantation should take these factors into
      account to minimize the risk of AR.

PMID- 22643106
TI  - Dynamic infrared thermography: a useful tool in the preoperative planning of deep
      inferior epigastric perforator flaps.

PMID- 22643108
TI  - Comment from editor on the letters of de Weerde et al and Chubb, et al.

PMID- 22643109
TI  - Commentary: End-to-end versus end-to-side motor and sensory neurorrhaphy in the
      repair of acute muscle denervation.

PMID- 22643110
TI  - Comparative analysis of microarray data in Arabidopsis transcriptome during
      compatible interactions with plant viruses.
AB  - BACKGROUND: At the moment, there are a number of publications describing gene
      expression profiling in virus-infected plants. Most of the data are limited to
      specific host-pathogen interactions involving a given virus and a model host
      plant - usually Arabidopsis thaliana. Even though several summarizing attempts
      have been made, a general picture of gene expression changes in susceptible virus
      host interactions is lacking. METHODS: To analyze transcriptome response to virus
      infection, we have assembled currently available microarray data on changes in
      gene expression levels in compatible Arabidopsis-virus interactions. We used the
      mean r (Pearson's correlation coefficient) for neighboring pairs to estimate
      pairwise local similarity in expression in the Arabidopsis genome. RESULTS: Here
      we provide a functional classification of genes with altered expression levels.
      We also demonstrate that responsive genes may be grouped or clustered based on
      their co-expression pattern and chromosomal location. CONCLUSIONS: In summary, we
      found that there is a greater variety of upregulated genes in the course of viral
      pathogenesis as compared to repressed genes. Distribution of the responsive genes
      in combined viral databases differed from that of the whole Arabidopsis genome,
      thus underlining a role of the specific biological processes in common mechanisms
      of general resistance against viruses and in physiological/cellular changes
      caused by infection. Using integrative platforms for the analysis of gene
      expression data and functional profiling, we identified overrepresented
      functional groups among activated and repressed genes. Each virus-host
      interaction is unique in terms of the genes with altered expression levels and
      the number of shared genes affected by all viruses is very limited. At the same
      time, common genes can participate in virus-, fungi- and bacteria-host
      interaction. According to our data, non-homologous genes that are located in
      close proximity to each other on the chromosomes, and whose expression profiles
      are modified as a result of the viral infection, occupy 12% of the genome. Among
      them 5% form co-expressed and co-regulated clusters.

PMID- 22643111
TI  - Attractiveness of employment sectors for physical therapists in Ontario, Canada
      (1999-2007): implication for the long term care sector.
AB  - BACKGROUND: Recruiting and retaining health professions remains a high priority
      for health system planners. Different employment sectors may vary in their appeal
      to providers. We used the concepts of inflow and stickiness to assess the
      relative attractiveness of sectors for physical therapists (PTs) in Ontario,
      Canada. Inflow was defined as the percentage of PTs working in a sector who were
      not there the previous year. Stickiness was defined as the transition probability
      that a physical therapist will remain in a given employment sector year-to-year.
      METHODS: A longitudinal dataset of registered PTs in Ontario (1999-2007) was
      created, and primary employment sector was categorized as 'hospital',
      'community', 'long term care' (LTC) or 'other.' Inflow and stickiness values were
      then calculated for each sector, and trends were analyzed. RESULTS: There were
      5003 PTs in 1999, which grew to 6064 by 2007, representing a 21.2% absolute
      growth. Inflow grew across all sectors, but the LTC sector had the highest inflow
      of 32.0%. PTs practicing in hospitals had the highest stickiness, with 87.4% of
      those who worked in this sector remaining year-to-year. The community and other
      employment sectors had stickiness values of 78.2% and 86.8% respectively, while
      the LTC sector had the lowest stickiness of 73.4%. CONCLUSION: Among all
      employment sectors, LTC had highest inflow but lowest stickiness. Given expected
      increases in demand for services, understanding provider transitional
      probabilities and employment preferences may provide a useful policy and planning
      tool in developing a sustainable health human resource base across all employment
      sectors.

PMID- 22643112
TI  - Epidemiology of Taenia solium in Nepal: is it influenced by the social
      characteristics of the population and the presence of Taenia asiatica?
AB  - The transmission of the zoonotic pork tapeworms Taenia solium and T. asiatica
      depends on a combination of specific risk factors, such as open defecation,
      backyard pig raising and the consumption of raw or undercooked pork and viscera.
      A community-based survey was conducted among 289 households in south-eastern
      Nepal to study the heterogeneity of these risk factor frequencies as a function
      of the social composition of the population. The frequency of open defecation,
      backyard pig raising and pork consumption differed significantly (P < 0.005)
      among the different coexisting caste and ethnic groups. In the same survey, the
      taeniosis prevalence was examined among the different groups. Tapeworm carriers
      were identified at a high prevalence among the Dum, one of the most disadvantaged
      communities of Nepal. A PCR-RFLP assay revealed that all collected tapeworm
      specimens were T. asiatica, a species thus far not known to occur in South Asia.
      These results can help to understand the epidemiology of T. solium in Nepal,
      which appears to be more complex than thought so far.

PMID- 22643113
TI  - Template method synthesis of mesoporous carbon spheres and its applications as
      supercapacitors.
AB  - Mesoporous carbon spheres (MCS) have been fabricated from structured mesoporous
      silica sphere using chemical vapor deposition (CVD) with ethylene as a carbon
      feedstock. The mesoporous carbon spheres have a high specific surface area of
      666.8 m2/g and good electrochemical properties. The mechanism of formation
      mesoporous carbon spheres (carbon spheres) is investigated. The important thing
      is a surfactant hexadecyl trimethyl ammonium bromide (CTAB), which accelerates
      the process of carbon deposition. An additional advantage of this surfactant is
      an increase the yield of product. These mesoporous carbon spheres, which have
      good electrochemical properties is suitable for supercapacitors.

PMID- 22643114
TI  - Hydrodynamics of the CertasTM programmable valve for the treatment of
      hydrocephalus.
AB  - BACKGROUND: The new CertasTM shunt for the treatment of hydrocephalus has seven
      standard pressure settings that according to the manufacturer range from 36 to
      238 mmH2O, and an additional "Virtual Off" setting with an opening pressure >400
      mmH2O. Information on actual pressure response and reliability of shunt
      performance is important in clinical application, especially the "Virtual Off"
      setting as a non-surgical replacement for shunt ligation. The objective of this
      study was to evaluate the in-vitro hydrodynamic performance of the CertasTM
      shunt. METHODS: Six new CertasTM shunts with proximal and distal catheters were
      tested with an automated, computerized test system that raised the pressure from
      zero to a maximum pressure and back to zero at each valve setting. Opening
      pressure and flow resistance were determined. RESULTS: For settings 1-7 the
      measured opening pressure range was 26 to 247 mmH2O, and the mean change in
      opening pressure for a one-step adjustment was between 33 and 38 mmH2O. For
      setting 8 ("Virtual Off") the measured mean opening pressure was 494 +/- 34 mmH2O
      (range 451 to 556 mmH2O). The mean outflow resistance was 7.0 mmHg/ml/min
      (outflow conductance 17.9 MUl/s/kPa). CONCLUSIONS: The six shunts had similar
      characteristics and closely matched the manufacturer's specifications for opening
      pressure at settings 1-7. The opening pressure for the "Virtual Off" setting was
      nearly 500 mmH2O, which is 100 mmH2O higher than the manufacturer's specification
      of ">400" and should be functionally off for most patients with communicating
      hydrocephalus. Clinical studies are needed to evaluate if the CSF dynamic profile
      persists after implantation in patients.

PMID- 22643115
TI  - Adipose tissue and breast epithelial cells: a dangerous dynamic duo in breast
      cancer.
AB  - Among the many different cell types surrounding breast cancer cells, the most
      abundant are those that compose mammary adipose tissue, mainly mature adipocytes
      and progenitors. New accumulating recent evidences bring the tumor-surrounding
      adipose tissue into the light as a key component of breast cancer progression.
      The purpose of this review is to emphasize the role that adipose tissue might
      play by locally affecting breast cancer cell behavior and subsequent clinical
      consequences arising from this dialog. Two particular clinical aspects are
      addressed: obesity that was identified as an independent negative prognostic
      factor in breast cancer and the oncological safety of autologous fat transfer
      used in reconstructive surgery for breast cancer patients. This is preceded by
      the overall description of adipose tissue composition and function with special
      emphasis on the specificity of adipose depots and the species differences, key
      experimental aspects that need to be taken in account when cancer is considered.

PMID- 22643116
TI  - Expression of insulin-like growth factor II mRNA-binding protein 3 in squamous
      cell carcinomas of the head and neck.
AB  - BACKGROUND: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) was found
      overexpressed in various cancer types suggesting its possible role in
      carcinogenesis. Analysis of IMP3 expression in head and neck squamous cell
      carcinomas (HNSCC) is rare so that we evaluated it using tissue microarray
      method. METHOD: Immunohistochemical analysis of IMP3 was performed on samples
      from over 400 patients. The expression was measured semiquantitative,
      subsequently divided into four categories (negative, weak, medium, or strong) and
      correlated with several available clinicopathologic parameters. RESULTS: For
      HNSCC, positive IMP3 expression was observed in patients with all tumor stages
      (pT1-4) and nodal stages (pN0-3), showing also significant statistical
      correlation (P=0.023 and P=0.0013, respectively). No further correlations were
      found. Separate analysis according to tumor localization (oral cavity,
      oropharyngeal, and laryngeal) showed a significant correlation of positive IMP3
      expression and overall survival (P=0.038) only in patients with tumors of the
      oral cavity. Multivariate analysis showed IMP3 as an independent predictive
      marker for oral squamous cell carcinomas (OSCC). CONCLUSION: Insulin-like growth
      factor II mRNA-binding protein 3 (IMP3) expression might be used as an
      independent prognostic factor in the subgroup of OSCC.

PMID- 22643117
TI  - MicroRNA profiling of a CD133(+) spheroid-forming subpopulation of the OVCAR3
      human ovarian cancer cell line.
AB  - BACKGROUND: Cancer stem cells (CSCs) are thought to be a source of tumor
      recurrence due to their stem cell-like properties. MicroRNAs (miRNAs) regulate
      both normal stem cells and CSCs, and dysregulation of miRNAs has an important
      role in tumorigenesis. Cluster of differentiation (CD) 133(+) and spheroid
      formation have been reported to be one of the main features of ovarian CSCs.
      Therefore, we determined the miRNA expression profile of a CD133(+) spheroid
      forming subpopulation of the OVCAR3 human ovarian cancer cell line. METHODS:
      Initially, we confirmed the enrichment of the OVCAR3 CD133 subpopulation by
      evaluating in vitro anchorage-independent growth. After obtaining a subpopulation
      of CD133(+) OVCAR3 cells with > 98% purity via cell sorting, miRNA microarray and
      real-time reverse transcription-polymerase chain reaction (RT-PCR) were performed
      to evaluate its miRNA profile. RESULTS: We found 37 differentially expressed
      miRNAs in the CD133(+) spheroid-forming subpopulation of OVCAR3 cells, 34 of
      which were significantly up-regulated, including miR-205, miR-146a, miR-200a, miR
      200b, and miR-3, and 3 of which were significantly down-regulated, including miR
      1202 and miR-1181. CONCLUSIONS: Our results indicate that dysregulation of miRNA
      may play a role in the stem cell-like properties of ovarian CSCs.

PMID- 22643118
TI  - Frequency and predictability effects in the Dundee Corpus: an eye movement
      analysis.
AB  - Analyses carried out on a large corpus of eye movement data were used to comment
      on four contentious theoretical issues. The results provide no evidence that word
      frequency and word predictability have early interactive effects on inspection
      time. Contrary to some earlier studies, in these data there is little evidence
      that properties of a prior word generally spill over and influence current
      processing. In contrast, there is evidence that both the frequency and the
      predictability of a word in parafoveal vision influence foveal processing. In the
      case of predictability, the direction of the effect suggests that more
      predictable parafoveal words produce longer foveal fixations. Finally, there is
      evidence that information about word class modulates processing over a span
      greater than a single word. The results support the notion of distributed
      parallel processing.

PMID- 22643119
TI  - Failure to learn from repeated mistakes: persistent decision-making impairment as
      measured by the iowa gambling task in patients with ventromedial prefrontal
      cortex lesions.
AB  - Although frontal patients show impaired decision-making on the Iowa Gambling Task
      (IGT), there has been no follow-up study to date to determine whether there is
      recovery of function over time. We examined neurological participants'
      performance on repeated administrations of the IGT over the course of 6 years. We
      found that, while non-neurological participants showed considerable improvement
      due to practice effects on the IGT, patients with ventromedial prefrontal cortex
      (VMPFC) damage persisted in showing impaired performance on each retest. These
      results validate the clinical observations that VMPFC dysfunction does not appear
      to be subject to autonomous recovery over time in real-life. (JINS, 2012, 18, 1
      4).

PMID- 22643120
TI  - What are the barriers to scaling up health interventions in low and middle income
      countries? A qualitative study of academic leaders in implementation science.
AB  - BACKGROUND: Most low and middle income countries (LMICs) are currently not on
      track to reach the health-related Millennium Development Goals (MDGs). One way to
      accelerate progress would be through the large-scale implementation of evidence
      based health tools and interventions. This study aimed to: (a) explore the
      barriers that have impeded such scale-up in LMICs, and (b) lay out an
      "implementation research agenda"--a series of key research questions that need to
      be addressed in order to help overcome such barriers. METHODS: Interviews were
      conducted with fourteen key informants, all of whom are academic leaders in the
      field of implementation science, who were purposively selected for their
      expertise in scaling up in LMICs. Interviews were transcribed by hand and
      manually coded to look for emerging themes related to the two study aims.
      Barriers to scaling up, and unanswered research questions, were organized into
      six categories, representing different components of the scaling up process:
      attributes of the intervention; attributes of the implementers; scale-up
      approach; attributes of the adopting community; socio-political, fiscal, and
      cultural context; and research context. RESULTS: Factors impeding the success of
      scale-up that emerged from the key informant interviews, and which are areas for
      future investigation, include: complexity of the intervention and lack of
      technical consensus; limited human resource, leadership, management, and health
      systems capacity; poor application of proven diffusion techniques; lack of
      engagement of local implementers and of the adopting community; and inadequate
      integration of research into scale-up efforts. CONCLUSIONS: Key steps in
      expanding the evidence base on implementation in LMICs include studying how to:
      simplify interventions; train "scale-up leaders" and health workers dedicated to
      scale-up; reach and engage communities; match the best delivery strategy to the
      specific health problem and context; and raise the low profile of implementation
      science.

PMID- 22643121
TI  - Integrated systems view on networking by hormones in Arabidopsis immunity reveals
      multiple crosstalk for cytokinin.
AB  - Phytohormones signal and combine to maintain the physiological equilibrium in the
      plant. Pathogens enhance host susceptibility by modulating the hormonal balance
      of the plant cell. Unlike other plant hormones, the detailed role of cytokinin in
      plant immunity remains to be fully elucidated. Here, extensive data mining,
      including of pathogenicity factors, host regulatory proteins, enzymes of hormone
      biosynthesis, and signaling components, established an integrated signaling
      network of 105 nodes and 163 edges. Dynamic modeling and system analysis
      identified multiple cytokinin-mediated regulatory interactions in plant disease
      networks. This includes specific synergism between cytokinin and salicylic acid
      pathways and previously undiscovered aspects of antagonism between cytokinin and
      auxin in plant immunity. Predicted interactions and hormonal effects on plant
      immunity are confirmed in subsequent experiments with Pseudomonas syringae pv
      tomato DC3000 and Arabidopsis thaliana. Our dynamic simulation is instrumental in
      predicting system effects of individual components in complex hormone disease
      networks and synergism or antagonism between pathways.

PMID- 22643122
TI  - The MEKK1-MKK1/MKK2-MPK4 kinase cascade negatively regulates immunity mediated by
      a mitogen-activated protein kinase kinase kinase in Arabidopsis.
AB  - In Arabidopsis thaliana, the MEKK1-MKK1/MKK2-MPK4 mitogen-activated protein (MAP)
      kinase cascade represses cell death and immune responses. In mekk1, mkk1 mkk2,
      and mpk4 mutants, programmed cell death and defense responses are constitutively
      activated, but the mechanism by which MEKK1, MKK1/MKK2, and MPK4 negatively
      regulate cell death and immunity was unknown. From a screen for suppressors of
      mkk1 mkk2, we found that mutations in suppressor of mkk1 mkk2 1 (summ1) suppress
      the cell death and defense responses not only in mkk1 mkk2 but also in mekk1 and
      mpk4. SUMM1 encodes the MAP kinase kinase kinase MEKK2. It interacts with MPK4
      and is phosphorylated by MPK4 in vitro. Overexpression of SUMM1 activates cell
      death and defense responses that are dependent on the nucleotide binding-leucine
      rich repeat protein SUMM2. Taken together, our data suggest that the MEKK1
      MKK1/MKK2-MPK4 kinase cascade negatively regulates MEKK2 and activation of MEKK2
      triggers SUMM2-mediated immune responses.

PMID- 22643123
TI  - Brain Gains: a literature review of medical missions to low and middle-income
      countries.
AB  - BACKGROUND: Healthcare professionals' participation in short-term medical
      missions to low and middle income countries (LMIC) to provide healthcare has
      become common over the past 50 years yet little is known about the quantity and
      quality of these missions. The aim of this study was to review medical mission
      publications over 25 years to better understand missions and their potential
      impact on health systems in LMICs. METHODS: A literature review was conducted by
      searching Medline for articles published from 1985-2009 about medical missions to
      LMICs, revealing 2512 publications. Exclusion criteria such as receiving country
      and mission length were applied, leaving 230 relevant articles. A data extraction
      sheet was used to collect information, including sending/receiving countries and
      funding source. RESULTS: The majority of articles were descriptive and lacked
      contextual or theoretical analysis. Most missions were short-term (1 day - 1
      month). The most common sending countries were the U.S. and Canada. The top
      destination country was Honduras, while regionally Africa received the highest
      number of missions. Health care professionals typically responded to presenting
      health needs, ranging from primary care to surgical relief. Cleft lip/palate
      surgeries were the next most common type of care provided. CONCLUSIONS: Based on
      the articles reviewed, there is significant scope for improvement in mission
      planning, monitoring and evaluation as well as global and/or national policies
      regarding foreign medical missions. To promote optimum performance by mission
      staff, training in such areas as cross-cultural communication and contextual
      realities of mission sites should be provided. With the large number of missions
      conducted worldwide, efforts to ensure efficacy, harmonisation with existing
      government programming and transparency are needed.

PMID- 22643124
TI  - Resistant to amyloid-beta or just waiting for disease to happen?
AB  - The post-mortem finding of abundant intracerebral accumulation of amyloid-beta
      (Abeta) in the cerebral cortex of some people who develop minimal neurofibrillary
      pathology and remain cognitively intact until death (so-called pathological
      aging, or PA) challenges the orthodox view of the pathogenesis of Alzheimer's
      disease (AD). This issue of Alzheimer's Research and Therapy reports a study by
      Moore and colleagues, of the McKnight Brain Institute (Gainesville, FL, USA) and
      the Mayo Clinic College of Medicine (Jacksonville, FL, USA), who have performed
      the most detailed analysis to date of the levels and types of Abeta that
      accumulate in such cases. Although the levels of the different forms of Abeta in
      prefrontal cortex from patients with AD tended to be higher than those from
      patients with PA, the authors found extensive overlap between the two groups and
      suggest that PA is likely to represent a prodromal stage of AD. It is also
      possible that the quantity of Abeta is less important than the extent to which it
      accumulates intraneuronally or that some people are resistant to its effects -
      perhaps because of genetically determined differences in the inflammatory and
      astrocytic reactions to Abeta. The study emphasizes the continuing importance of
      careful human clinical and post-mortem studies in elucidating the pathogenesis of
      this disease.

PMID- 22643125
TI  - Differential susceptibility of Cx26 mutations associated with epidermal
      dysplasias to peptidoglycan derived from Staphylococcus aureus and Staphylococcus
      epidermidis.
AB  - Mutations in Connexin26 (Cx26) give rise to a spectrum of dominantly inherited
      hyperproliferating skin disorders, the severest being keratitis-ichthyosis
      deafness (KID) syndrome, an inflammatory skin disorder, with patients prone to
      opportunistic infections. We compared the effects of peptidoglycan (PGN)
      extracted from the skin commensal Staphylococcus epidermidis and the
      opportunistic pathogen Staphylococcus aureus on interleukin-6 and connexin
      expression in HaCaT cells (a keratinocyte cell line) and connexin channel
      activity in HaCaT and HeLa (connexin deficient) cells transfected to express KID
      and non-KID Cx26 mutations. In both cell types, PGN from S. aureus induced
      hemichannel activity in cells expressing KID mutants as monitored by ATP release
      assays following 15-min challenge, while that from S. epidermidis evoked a
      response in HeLa cells. In KID mutant expressing cells, ATP release was
      significantly higher than in cells transfected with wild-type Cx26. No ATP
      release was observed in non-KID mutant transfected cells or in the presence of
      carbenoxolone, a connexin channel blocker. PGN isolated from S. aureus but not S.
      epidermidis induced interleukin-6 and Cx26 expression in HaCaT cells following 6
      h challenge. Challenge by PGN from S. aureus evoked a greater interleukin-6
      response in cells expressing KID mutants than in cells expressing wtCx26 or non
      KID mutants. This response returned to basal levels if acute KID hemichannel
      signalling was blocked prior to PGN challenge. Thus, KID mutants form channels
      that can be triggered by the pro-inflammatory mediator PGN from opportunistic
      pathogens but not skin commensals, providing further insight into the genotype
      phenotype relationship of Cx26 disorders.

PMID- 22643126
TI  - Slipped capital femoral epiphysis following fracture of the femoral neck:  a case
      report.
AB  - Reports on cases of femoral neck fracture complicated by a slipped capital
      femoral epiphysis associated with avascular necrosis and coxa vara deformity in
      children are extremely rare. In this case report, we describe a patient who had
      complications of a slipped capital femoral epiphysis with avascular necrosis and
      coxa vara deformity after a Delbet type III left femoral neck fracture. We also
      describe the surgical treatment to overcome these complications.

PMID- 22643127
TI  - Complications of Albizzia femoral lengthening nail:  an analysis of 36 cases.
AB  - Thirty-six cases of femoral lengthening using the Albizzia nail were performed.
      The indication for lengthening was a congenital malformation, sequellae of
      trauma, of infection, of radiation therapy, short stature, and vascular
      malformation. The mean age of the patients was 16 years, the average lengthening
      achieved was 4.7 cm, and the follow-up period averaged 5.8 years. We found that
      bone consolidation was achieved faster than with external fixation. The patient's
      comfort during lengthening as well as the speed of functional restoration also
      improved. In three cases, the program failed, in six the lengthening was achieved
      with a second procedure, and eight patients required one ratcheting or more under
      general anesthesia. In our experience, the Albizzia nail is a simple and
      effective solution for uncomplicated femoral lengthening.

PMID- 22643128
TI  - Multicentric giant cell tumor in adolescents: three case reports.
AB  - The presentation of multicentric giant cell tumor in adolescents with an open
      physis is very rare. We report three cases of a multicentric giant cell tumor of
      the bone in adolescents, and a review of the literature is also presented.

PMID- 22643129
TI  - Neglected Hoffa fracture in a child.
AB  - The clinical presentations and surgical outcome of a 4-month-old Hoffa fracture
      in a 12-year-old child are reported. The child presented with chronic pain,
      swelling and instability in the right knee joint. Lateral radiograph showed a
      small bone fragment on the posterior condyle, which raised the possibility of a
      fracture. Computed tomographic scan and MRI clearly delineated the coronal plane
      fracture of the lateral femoral condyle that had spared the physeal cartilage.
      The fracture was accessed through the posterolateral approach to the knee; the
      fragment was anatomically reduced and fixed with two partially threaded
      cancellous screws. Radiographic union was observed after 3 months, and after 2
      years of follow-up, the child had excellent functional outcome.

PMID- 22643130
TI  - Numerical and physical magnitudes are mapped into time.
AB  - In two experiments we investigated mapping of numerical and physical magnitudes
      with temporal order. Pairs of digits were presented sequentially for a size
      comparison task. An advantage for numbers presented in ascending order was found
      when participants were comparing the numbers' physical and numerical magnitudes.
      The effect was more robust for comparisons of physical size, as it was found
      using both select larger and select smaller instructions, while for numerical
      comparisons it was found only for select larger instructions. Varying both the
      digits' numerical and physical sizes resulted in a size congruity effect,
      indicating automatic processing of the irrelevant magnitude dimension. Temporal
      order and the congruency between numerical and physical magnitudes affected
      comparisons in an additive manner, thus suggesting that they affect different
      stages of the comparison process.

PMID- 22643131
TI  - Association of CTXN3-SLC12A2 polymorphisms and schizophrenia in a Thai
      population.
AB  - BACKGROUND: A genome-wide association study (GWAS) combined with brain imaging as
      a quantitative trait analysis revealed that the SNPs near CTXN3-SLC12A2 region
      were related to forebrain development and stress response which involved in
      schizophrenia. In the present study, the SNPs in this region were analyzed for
      association with schizophrenia in a Thai population. METHODS: A total of 115
      schizophrenia and 173 unrelated normal controls with mean age of 37.87 +/- 11.8
      and 42.81 +/- 6.0 years, respectively, were included in this study. Genotyping
      was performed using polymerase chain reaction and high-resolution melting (HRM)
      analysis. The difference in genotype distribution between patient and control was
      assessed by Chi-square test of the SPSS software. RESULTS: We found a significant
      association between the GWAS-discovered SNP, rs245178, with the risk of
      schizophrenia in the Thai population [P = 0.006, odds ratio for the minor G
      allele: 0.62(0.46-0.83)]. Additionally, another potential SNP, rs698172, which
      was in moderate linkage disequilibrium with rs245178, also showed strong
      association with schizophrenia [P = 0.003, odds ratio for minor T allele:
      0.61(0.46-0.82)]. This association remained significant at 5% level after the
      Bonferroni correction for multiple testing. CONCLUSIONS: This study shows that
      two SNPs in intergenic of the CTXN3 and SLC12A2 genes, rs245178 and rs698172, are
      associated with risk of schizophrenia in Thai population. Further study is
      required for clarification the role of genetic variation around these SNPs in
      expression pattern of the CTXN3 and SLC12A2 genes, which may be involved in
      schizophrenia pathogenesis.

PMID- 22643132
TI  - Overnutrition and associated factors among adults aged 20 years and above in
      fishing communities in the urban Cape Coast Metropolis, Ghana.
AB  - OBJECTIVE: The study aimed to highlight the determinants of overnutrition
      (overweight plus obesity) in fishing communities and establish if these were the
      same as reported elsewhere in Ghana. DESIGN: Cross-sectional study. SETTING: The
      study was conducted in Idun, Ola and Duakor fishing communities in Cape Coast,
      Ghana. SUBJECTS: Adults (n 252) aged 20 to 50 years. RESULTS: Results showed that
      32 % of participants were overweight/obese (BMI >= 25.0 kg/m2). Participants'
      mean age was 31.7 (sd 1.0) years, they had 13.7 (sd 8.1) mean years of formal
      education, their median monthly income was $US 7.4 (interquartile range $US 3.3,
      20.0) and their median daily energy intake was 7.3 (interquartile range 5.3, 9.8)
      MJ. Significant associations (P < 0.05) were found between BMI and gender, age,
      years of education, fat intake and marital status. Females were almost eight
      times more likely to be overweight/obese than males (adjusted OR = 7.7; 95 % CI
      3.6, 16.4). Persons aged >=40 years were about six times more likely to be
      overweight/obese than those aged 20-29 years (adjusted OR = 6.1; 95 % CI 2.6,
      14.1). Married people were nearly three times more likely to be overweight/obese
      than singles (adjusted OR = 2.8; 95 % Cl 1.4, 5.7). People with more than 13
      years of formal education (adjusted OR = 0.3; 95 % CI 0.1, 0.9) and people with
      >30 % fat contribution to daily energy intake (adjusted OR = 0.3; 95 % CI 0.1,
      0.6) had reduced odds of being overweight/obese. CONCLUSIONS: Overnutrition was
      prevalent in the fishing communities and associated with factors such as age,
      gender, marital status, educational status and fat intake.

PMID- 22643133
TI  - Firing patterns of maternal rat prelimbic neurons during spontaneous contact with
      pups.
AB  - Extracellular single unit activity was recorded from medial prefrontal cortex
      (mPFC) of postpartum dams over the course of 3 days while they engaged in
      spontaneous pup-directed behaviors and non-specific exploratory behavior. Out of
      109 units identified over the course of the experiment, 15 units were observed to
      be pup-responsive and 15 increased their discharge rates non-specifically while
      not attending to pups. An association between neuronal activity and typical
      maternal behaviors (e.g., retrieval, pup-grooming, nursing) was not observed.
      Instead, brief bouts of snout contact with pups were accompanied by phasic
      increases and decreases in spike rates. The observed pup contact responsive cells
      might play a role in processing of sensory feedback from pups or the transmission
      of modulatory output to other subcortical maternal brain areas.

PMID- 22643135
TI  - Acute neuromuscular and metabolic responses to concurrent endurance and
      resistance exercise.
AB  - Metabolic and neurological responses to 4 bouts of lower-body or upper-body
      resistance exercise preceded by cycle ergometry or rest were assessed. Nine
      resistance-trained men (26.7 +/- 6.6 years) underwent bouts of (a) cycle
      ergometry then bench press, (b) bench press only, (c) cycle ergometry then back
      squat, and (d) back squat only. Cycle ergometry was performed at 75% maximum
      heart rate for 45 minutes. Bench press and back squat protocols required 6 sets
      to volitional fatigue at 80% 1RM with 2 minutes rest between sets. Significantly
      more repetitions were performed during set 1 for back squat without preceding
      aerobic exercise (12.6 +/- 4.5 vs. 10.0 +/- 3.5, p = 0.000) and cumulatively at
      set 3 (27.1 +/- 10.6 vs. 23.1 +/- 9.2, p = 0.014), and no differences were noted
      for bench press repetitions. Inclusion of cycle ergometry results in impaired
      back squat, but not bench press, performance likely because of a combination of
      local metabolic stress and various neuromuscular effects.

PMID- 22643136
TI  - Body composition and military performance--many things to many people.
AB  - Soldiers are expected to maintain the highest possible level of physical
      readiness because they must be ready to mobilize and perform their duties
      anywhere in the world at any time. The objective of Army body composition
      standards is to motivate physical training and good nutrition habits to ensure a
      high state of readiness. Establishment of enforceable and rational standards to
      support this objective has been challenging even at extremes of body size.
      Morbidly obese individuals are clearly not suited to military service, but very
      large muscular individuals may be superbly qualified for soldier performance
      demands. For this reason, large individuals are measured for body fat using a
      waist circumference-based equation (female soldiers are also measured for hip
      circumference). The main challenge comes in setting appropriate fat standards to
      support the full range of Army requirements. Military appearance ideals dictate
      the most stringent body fat standards, whereas health risk thresholds anchor the
      most liberal standards, and physical performance associations fall on a spectrum
      between these 2 poles. Standards should not exclude or penalize specialized
      performance capabilities such as endurance running or power lifting across a
      spectrum of body sizes and fat. The full integration of women into the military
      further complicates the issue because of sexually dimorphic characteristics that
      make gender-appropriate standards essential and where inappropriately stringent
      standards can compromise both health and performance of this segment of the
      force. Other associations with body composition such as stress effects on
      intraabdominal fat distribution patterns and metabolic implications of a fat
      reserve for survival in extreme environments are also relevant considerations.
      This is a review of the science that underpins the U.S. Army body composition
      standards.

PMID- 22643137
TI  - The relationship between maximal lifting capacity and maximum acceptable lift in
      strength-based soldiering tasks.
AB  - Psychophysical assessments, such as the maximum acceptable lift, have been used
      to establish worker capability and set safe load limits for manual handling tasks
      in occupational settings. However, in military settings, in which task demand is
      set and capable workers must be selected, subjective measurements are inadequate,
      and maximal capacity testing must be used to assess lifting capability. The aim
      of this study was to establish and compare the relationship between maximal
      lifting capacity and a self-determined tolerable lifting limit, maximum
      acceptable lift, across a range of military-relevant lifting tasks. Seventy male
      soldiers (age 23.7 +/- 6.1 years) from the Australian Army performed 7 strength
      based lifting tasks to determine their maximum lifting capacity and maximum
      acceptable lift. Comparisons were performed to identify maximum acceptable lift
      relative to maximum lifting capacity for each individual task. Linear regression
      was used to identify the relationship across all tasks when the data were pooled.
      Strong correlations existed between all 7 lifting tasks (rrange = 0.87-0.96, p <
      0.05). No differences were found in maximum acceptable lift relative to maximum
      lifting capacity across all tasks (p = 0.46). When data were pooled, maximum
      acceptable lift was equal to 84 +/- 8% of the maximum lifting capacity. This
      study is the first to illustrate the strong and consistent relationship between
      maximum lifting capacity and maximum acceptable lift for multiple single lifting
      tasks. The relationship developed between these indices may be used to help
      assess self-selected manual handling capability through occupationally relevant
      maximal performance tests.

PMID- 22643138
TI  - The development of a preselection physical fitness training program for Canadian
      Special Operations Regiment applicants.
AB  - Special Operations Forces (SOF) soldiers must undergo a rigorous selection
      process that requires high levels of physical fitness and stamina to complete.
      Physical preparedness is crucial for an applicant's performance during a
      selection process; preselection physical training programs for SOF applicants
      must be specific to the demands of the selection process. The purpose of this
      study was to analyze the physical demands of the Canadian Special Operations
      Regiment (CSOR) Assessment Center (AC) to develop an evidence-based physical
      fitness program to assist future applicants to CSOR with their physical
      preparation. Seventy-one men volunteered to undergo a battery of fitness tests
      before attending the CSOR AC. Forty-six (mean [SD]: age 26.2 [4.4] years, height
      176.5 [7.4] cm, body mass 82.4 [10.1] kg) of the 71 participants further
      volunteered to participate in the characterization of the physical demands of the
      AC. Heart rate (HR) data were collected during the physically demanding sessions,
      and a subsequent task and physiological analysis was conducted to determine key
      performance variables for exercise prescription. The physically demanding
      sessions ranged in length from 26.38 (4.24) minutes to 668.52 (30.09) minutes,
      with the mean HR data ranging from 169.81 (6.64) to 97.51 (6.65) b.min-1,
      respectively. Key predictors of completion of the AC were V[Combining Dot
      Above]O2peak (betaexp: 5.92; confidence interval [CI]: 1.1-31.0), and 1
      repetition maximum (1RM) squats (betaexp: 5.16; CI: 1.2-22.2). The information
      derived from this study provided the foundation for the design of an evidence
      based preparatory training program for future applicants that is reflective of
      the physical demands of the selection process.

PMID- 22643139
TI  - Automation to improve efficiency of field expedient injury prediction screening.
AB  - Musculoskeletal injuries are a primary source of disability in the U.S. Military.
      Physical training and sports-related activities account for up to 90% of all
      injuries, and 80% of these injuries are considered overuse in nature. As a
      result, there is a need to develop an evidence-based musculoskeletal screen that
      can assist with injury prevention. The purpose of this study was to assess the
      capability of an automated system to improve the efficiency of field expedient
      tests that may help predict injury risk and provide corrective strategies for
      deficits identified. The field expedient tests include survey questions and
      measures of movement quality, balance, trunk stability, power, mobility, and foot
      structure and mobility. Data entry for these tests was automated using handheld
      computers, barcode scanning, and netbook computers. An automated algorithm for
      injury risk stratification and mitigation techniques was run on a server
      computer. Without automation support, subjects were assessed in 84.5 +/- 9.1
      minutes per subject compared with 66.8 +/- 6.1 minutes per subject with
      automation and 47.1 +/- 5.2 minutes per subject with automation and process
      improvement measures (p < 0.001). The average time to manually enter the data was
      22.2 +/- 7.4 minutes per subject. An additional 11.5 +/- 2.5 minutes per subject
      was required to manually assign an intervention strategy. Automation of this
      injury prevention screening protocol using handheld devices and netbook computers
      allowed for real-time data entry and enhanced the efficiency of injury screening,
      risk stratification, and prescription of a risk mitigation strategy.

PMID- 22643140
TI  - From the subarctic to the tropics:  effects of 4-month deployment on soldiers'
      heat stress, heat strain, and physical performance.
AB  - The aim of the study was to evaluate the heat stress of Finnish male soldiers (N
      = 20, age 22.0 +/- 2.5 years, body mass 78.8 +/- 11.5 kg, and height 180.2 +/-
      5.6 cm) during their 4-month deployment in a hot environment and to find out the
      effects on physical performance and body composition. The troops moved from 2.5
      degrees  C (mean monthly temperature) in Finland to 31.9 degrees  C in Chad.
      During the deployment, temperatures varied between 13.5 and 57.0 degrees  C
      outdoors and in the vehicles and tents. During 1-day recording in the middle of
      the deployment, skin temperatures were 34-35 degrees  C during daytime and
      maximal core temperature remained mainly below 38.0 degrees  C. Body mass
      decreased (78.4 +/- 11.5 kg vs. 75.6 +/- 8.6, p = 0.007) during the deployment
      without changes in fat mass. The sit-up performance increased by 10.9% (46 +/- 10
      reps.min-1 vs. 51 +/- 7 reps.min-1, p < 0.01), and the maximal force production
      of the leg extensor muscles increased (3,042 +/- 614 N vs. 3,277 +/- 706 N, p <
      0.05) without change in the rate of force development. No changes were observed
      in the push-ups, repeated squats, maximal grip strength, and running distance
      during the 12-minute test. In conclusion, the soldiers were able to maintain or
      improve their physical performance during the deployment despite the heat stress.
      It is important to encourage soldiers to engage in physical training, especially
      during a thermally appropriate time of the day or in air-conditioned facilities.
      Monitoring of local heat stress is also recommended.

PMID- 22643141
TI  - IGF-I, IGFBPs, and inflammatory cytokine responses during gender-integrated
      Israeli Army basic combat training.
AB  - Insulin-like growth factor 1 (IGF-I) is a robust metabolic and anabolic biomarker
      that has been demonstrated to be reflective of military training-induced body
      composition changes and influenced by initial aerobic fitness level. Greater
      mechanistic insight into the IGF-I response to physical training can potentially
      be gleaned by also examining other regulatory factors that influence IGF-I
      biological activity (i.e., insulin-like growth factor-binding proteins [IGFBPs]
      and inflammatory cytokine responses). The purpose of this study was to assess the
      influence of sex and initial fitness level on the IGF-I and inflammatory cytokine
      response to gender-integrated Israeli Defense Forces (IDF) basic combat training
      (BCT). Recruits (29 men, 19.1 +/- 1.3 years; 93 women, 18.8 +/- 0.6 years) were
      recruited from a 4-month gender-integrated BCT of the IDF. Blood was drawn and
      assayed for total IGF-I, free IGF-I, IGFBPs 1-6, tumor necrosis factor alpha (TNF
      alpha), interleukin 6, and interleukin 1 beta. Body composition was determined
      via a 4-site skinfold (biceps, triceps, suprailiac, and subscapular) equation.
      Physical performance was assessed via a maximum volume of oxygen consumption
      (V[Combining Dot Above]O2max) test using a treadmill protocol. All measures were
      obtained pre- and posttraining. A 2-way (sex * time) analysis of variance was
      used to test for statistical differences (p <= 0.05). Additionally, subjects were
      further partitioned (men and women separately) by tertiles of initial V[Combining
      Dot Above]O2max to assess the influence of initial fitness level on the IGF-I
      system and inflammatory cytokine responses to physical training. Pearson product
      moment correlational analysis was also used to examine relationships between
      percent changes in blood measures and physical performance and body composition
      changes. All data are presented as mean +/- SE. Time effects were observed only
      for total IGF-I, IGFBP-2, TNF-alpha, V[Combining Dot Above]O2max, fat-free mass,
      and fat mass. The only significant (p <= 0.05) correlations observed for percent
      changes were in men between total IGF-I and V[Combining Dot Above]O2max (r =
      0.49) and body mass (r = -0.42) During gender-integrated Israeli Army BCT, men
      and women generally respond in a similar fashion with regard to blood measures
      (IGF-I system and inflammatory cytokines) and V[Combining Dot Above]O2max.
      Initial fitness level only influenced the IGF-I response to training in women.
      Although the training-induced changes in total IGF-I (increase), IGFBP-2
      (decrease), and TNF-alpha (decrease) are all indicative of an enhanced
      circulating anabolic milieu, only total IGF-I for the men was correlated with
      body composition and fitness improvements.

PMID- 22643142
TI  - Strength training for the warfighter.
AB  - Optimizing strength training for the warfighter is challenged by past training
      philosophies that no longer serve the modern warfighter facing the "anaerobic
      battlefield." Training approaches for integration of strength with other needed
      physical capabilities have been shown to require a periodization model that has
      the flexibility for changes and is able to adapt to ever-changing circumstances
      affecting the quality of workouts. Additionally, sequencing of workouts to limit
      over-reaching and development of overtraining syndromes that end in loss of duty
      time and injury are paramount to long-term success. Allowing adequate time for
      rest and recovery and recognizing the negative influences of extreme exercise
      programs and excessive endurance training will be vital in moving physical
      training programs into a more modern perspective as used by elite strength-power
      anaerobic athletes in sports today. Because the warfighter is an elite athlete,
      it is time that training approaches that are scientifically based are updated
      within the military to match the functional demands of modern warfare and are
      given greater credence and value at the command levels. A needs analysis,
      development of periodized training modules, and individualization of programs are
      needed to optimize the strength of the modern warfighter. We now have the
      knowledge, professional coaches and nonprofit organization certifications with
      continuing education units, and modern training technology to allow this to
      happen. Ultimately, it only takes command decisions and implementation to make
      this possible.

PMID- 22643143
TI  - The physical demands placed on modern soldiers continue to be substantial.
      Preface.

PMID- 22643144
TI  - A bout of resistance exercise following the 2007 AHA guidelines decreases asleep
      blood pressure in Mozambican men.
AB  - Hypertension is highly prevalent among African individuals and descendants, and
      in this ethnic group, asleep blood pressure is strongly associated with target
      organ damage. After its execution, a single bout of resistance exercise may
      decrease blood pressure in white individuals, but its effects are unknown in
      Africans. This study investigated the effects of a bout of resistance exercise,
      conducted in accordance with the 2007 American Heart Association (AHA)
      guidelines, on postexercise blood pressure in African subjects. Twenty-four
      Mozambican men (40 +/- 2 years) underwent, in a random order, 2 experimental
      sessions: control (sitting resting) and exercise [8 resistance exercises, 1 set,
      10-15 repetitions, 30-40% of 1 repetition maximum (1RM) for upper-body muscles
      and 50-60% of 1RM for lower-body muscles]. Before and after the interventions,
      clinic blood pressure was measured. Ambulatory blood pressure was also evaluated
      after both sessions. Clinic systolic blood pressure did not change after both
      interventions, whereas diastolic blood pressure increased significantly and
      similarly after the control and the exercise sessions. Twenty-four-hour (127 +/-
      3 mm Hg vs. 130 +/- 3 mm Hg and 78 +/- 2 mm Hg vs. 81 +/- 2 mm Hg, respectively,
      p < 0.05) and asleep (119 +/- 4 mm Hg vs. 123 +/- 4 mm Hg and 69 +/- 3 mm Hg vs.
      72 +/- 3 mm Hg, respectively, p < 0.05) systolic and diastolic blood pressures
      were lower after the exercise than in the control session. These results show
      that in African men, a single bout of resistance exercise, conducted in
      accordance with 2007 AHA guidelines, decreased 24-hour and asleep blood
      pressures. These reductions might represent an important benefit for African
      individuals and descendants among whom target organ damage is mainly associated
      with ambulatory blood pressure levels.

PMID- 22643146
TI  - Peak power prediction in junior basketballers: comparing linear and allometric
      models.
AB  - Equations, commonly used to predict peak power from jump height, have relied on
      linear additive models that are biologically unsound beyond the range of
      observations because of high negative intercept values. This study explored the
      utility of allometric multiplicative modeling to better predict peak power in
      adolescent basketball players. Seventy-seven elite junior basketball players (62
      adolescent boys, 15 adolescent girls, age = 16.8 +/- 0.8 years) performed 3
      counter movement jumps (CMJs) on a force platform. Both linear and multiplicative
      models were then used to determine their efficacy. Four previously published
      linear equations were significantly associated with actual peak power (all p <
      0.01), although here were significant differences between actual and estimated
      peak power using the SJ and CMJ equations by Sayers (both p < 0.001). Allometric
      modeling was used to determine an alternative biologically sound equation which
      was more strongly associated with (r = 0.886, p < 0.001), and not significantly
      different to (p > 0.05), actual peak power and predicted 77.9% of the variance in
      actual peak power (adjusted R = 0.779, p < 0.001). Exponents close to 1 for body
      mass and CMJ height indicated that peak power could also be determined from the
      product of body mass and CMJ height. This equation was significantly associated
      (r = 0.871, p < 0.001) with, and not significantly different to, actual peak
      power (adjusted R = 0.756, p > 0.05) and offered a more accurate estimation of
      peak power than previously validated linear additive models examined in this
      study. The allometric model determined from this study or the multiplicative
      model (body mass * CMJ height) provides biologically sound models to accurately
      estimate peak power in elite adolescent basketballers that are more accurate than
      equations based on linear additive models.

PMID- 22643148
TI  - Too much health care and too little care for the sick?

PMID- 22643149
TI  - General practitioners' strategies to identify alcohol problems: a focus group
      study.
AB  - OBJECTIVE: To explore general practitioners' (GPs') experiences with addressing
      alcohol in the consultation without prior invitation from the patient. DESIGN AND
      SETTING: Two focus group interviews were conducted with a purposive sample of 13
      Norwegian GPs in the Stavanger region. Participants were invited to talk about
      situations where the doctor initiated discussion of alcohol. Systematic text
      condensation was applied for analysis. RESULTS: Participants presented a broad
      range of examples of what made GPs initiate discussion of alcohol, how they
      brought up the subject, and what happened when they did so. Sometimes they were
      just acting on a hunch. Family members were also occasionally prompting the
      doctor to act, or recent serious incidents worked as cues for asking. Routinely
      taking or creating an opportunity to explore was also common. Directly
      confronting the patient was a challenging task, and the participants disclosed
      experiences of how this had been achieved. CONCLUSIONS: Pragmatic case-finding
      appears to be a field of competence which can be further developed, but should be
      adapted to the clinical setting and the GP's personal style. It is suggested that
      strategies for dealing with alcohol problems in general practice should be based
      on a proper understanding of this specific medical context, and be adaptable to
      different clinical situations and the individual patient.

PMID- 22643150
TI  - Reasons for encounter and disease patterns in Danish primary care: changes over
      16 years.
AB  - OBJECTIVE: Approximately 98% of Danish citizens are listed with a general
      practice which they consult for medical advice. Although 85% of the population
      contact their general practitioner (GP) every year, little is known about these
      contacts. The aim of the present paper is to gain updated knowledge about
      patients' reasons for encounter and the GP activities and to make comparisons
      with a similar study from 1993. METHODS: All GPs in the Central Denmark Region
      were invited to register all contacts during one randomly chosen day within a
      year. The registration included questions about patients' reasons for encounter,
      the types and contents of the contacts, referrals, and distribution between new
      episodes and follow-up contacts. Aggregated data were compared with the results
      from 1993. RESULTS: A total of 404 (46%) GPs participated. The number of contacts
      per 1000 inhabitants had risen by 19.7%. The reasons for encounter and final
      diagnoses resembled those in 1993. Musculoskeletal, psychological, and
      respiratory problems were the most common reasons for encounter, psychological
      problems being the only type to increase over the period. Interestingly, the
      proportion of diagnoses within the ICPC 'A' chapter rose from 13.5 to 19.7%. The
      referral rate rose by 2% (relative: 18.7%) from 10.7% to 12.7% and the share of
      follow-up contacts rose from 45.9% to 50.4% (relative: 8.7%). CONCLUSION: Quite
      small changes were seen in the patterns of reasons for encounter and diagnoses
      from 1993 to 2009. However, an increase was found in contacts with general
      practice and referrals and in the proportion of follow-ups.

PMID- 22643151
TI  - Use of laboratory tests in out-of-hours services in Norway.
AB  - OBJECTIVE: To investigate the use of laboratory tests and which factors influence
      the use in Norwegian out-of-hours (OOH) services. DESIGN: Cross-sectional
      observational study. SETTING: Out-of-hours services in Norway. SUBJECTS: All
      electronic reimbursement claims from doctors at OOH services in Norway in 2007.
      MAIN OUTCOME MEASURES: Number of contacts and laboratory tests in relation to
      patients' and doctors' characteristics. RESULTS: 1 323 281 consultations and home
      visits were reported. Laboratory tests were used in 31% of the contacts. C
      reactive protein (CRP) was the most common test (27% of all contacts), especially
      in respiratory illness (55%) and infants (44%). Electrocardiogram and rapid strep
      A test were used in 4% of the contacts. Young doctors, female doctors, and
      doctors in central areas used laboratory tests more often. CONCLUSION: CRP is
      extensively used in OOH services, especially by young and inexperienced doctors,
      and in central areas. Further investigations are required to see if this
      extensive use of CRP is of importance for correct diagnosis and treatment.

PMID- 22643152
TI  - How to diagnose and classify diabetes in primary health care: lessons learned
      from the Diabetes Register in Northern Sweden (DiabNorth).
AB  - OBJECTIVE: The objective was to create a diabetes register and to evaluate the
      validity of the clinical diabetes diagnosis and its classification. DESIGN: The
      diabetes register was created by linkage of databases in primary and secondary
      care, the pharmaceutical database, and ongoing population-based health surveys in
      the county. Diagnosis and classification were validated by specialists in
      diabetology or general practitioners with special competence in diabetology.
      Analysis of autoantibodies associated with type 1 diabetes was used for
      classification. SETTING: Primary and secondary health care in the county of
      Vasterbotten, Sweden. PATIENTS: Patients with diabetes (median age at diagnosis
      56 years, inter quartile range 50-60 years) who had participated in the
      Vasterbotten Intervention Programme (VIP) and accepted participation in a
      diabetes register. RESULTS: Of all individuals with diabetes in VIP, 70% accepted
      to participate in the register. The register included 3256 (M/F 1894/1362)
      diabetes patients. The vast majority (95%) had data confirming the diabetes
      diagnoses according to WHO recommendations. Unspecified diabetes was the most
      common (54.6%) classification by the general practitioners. After assessment by
      specialists and analysis of autoantibodies the majority were classified as type 2
      diabetes (76.8%). Type 1 diabetes was the second largest group (7.2%), including
      a sub-group of patients with latent autoimmune diabetes (4.8%). CONCLUSION: It
      was concluded that it is feasible to create a diabetes register based on
      information in medical records in general practice. However, special attention
      should be paid to the validity of the diabetes diagnosis and its classification.

PMID- 22643154
TI  - Aerobic performance and body composition changes during military service.
AB  - OBJECTIVE: To examine the association between aerobic performance and body
      composition changes by body mass index (BMI). DESIGN: 6-12 months' follow-up
      during military service. SETTING: Conscripts entering military service in 2005 in
      Sodankyla Jaeger Brigade (Finland). SUBJECTS: 945 men (19 years, SD 1 years).
      MAIN OUTCOME MEASURES: Height, weight, waist circumference, BMI, and aerobic
      performance (Cooper test) were recorded. Body composition was measured by
      bioelectrical impedance analysis (BIA). The measured parameters were fat mass
      (FM), fat free mass (FFM), and visceral fat area (VFA). All the measurements were
      performed at the beginning and end of service. RESULTS: On average, the military
      training period improved the running distance by 6.8% (169 m, p < 0.001) and the
      improvements were more pronounced in overweight (223.9 m/9.5%, p < 0.001) and
      obese (273.3 m/13.6%, p < 0.001) conscripts. A strong inverse correlation between
      aerobic performance and body composition changes was observed, especially for
      weight (r = -0.305, p < 0.001) and VFA (r = -0.465, p < 0.001). A significant
      association between aerobic performance and changes in weight (p < 0.001), waist
      circumference (p < 0.001), FM (p < 0.001), and VFA (p < 0.001) by BMI was
      detected. The associated decrease in weight, waist circumference, FM, and VFA
      with improved aerobic performance was more substantial between overweight and
      obese compared with normal-weight subjects. CONCLUSIONS: Favourable changes in
      body composition are associated with improved aerobic performance during a
      physical training period such as military service. These findings are pronounced
      among overweight and obese men and can be applied at the population level in
      reducing obesity and co-morbidities.

PMID- 22643153
TI  - Prevalence, awareness, treatment, and control of hypertension: rule of thirds in
      the Skaraborg project.
AB  - OBJECTIVE: To describe the prevalence, awareness, and control of hypertension in
      a Swedish population during the early 2000s to address implications for care and
      prevention. DESIGN: A cross-sectional population survey. SETTING: Primary health
      care in Skaraborg, a rural part of western Sweden. SUBJECTS: Participants (n
      =2816) in a population survey of a random sample of men and women between 30 and
      75 years of age in the municipalities of Vara (81% participation rate) and Skovde
      (70%), in western Sweden during 2001-2005. MAIN OUTCOME MEASURES: Anthropometric
      measures, blood pressure, leisure-time physical activity, current smoking,
      fasting glucose, and cholesterol. Hypertension was defined as ongoing treatment
      for hypertension, or three consecutive blood pressure readings >=140 systolic
      and/or >=90 mmHg diastolic. Hypertension was considered controlled when the blood
      pressure was <140/90 mm Hg (both). RESULTS: The prevalence of hypertension was
      20% in both men and women with a steep increase by age. Among hypertensive
      subjects, 33% were unaware, 36% aware but uncontrolled, and 31% aware and
      controlled, with no statistically significant differences between men and women.
      Patients with diabetes had a higher awareness (87% vs. 64%, p <0.001), but the
      same control rate (56% vs. 44%, p =0.133), when compared with those without
      diabetes. CONCLUSION: A large proportion of subjects with hypertension are still
      unaware of their condition, or aware but not controlled. It is important to
      emphasize population-based prevention to reduce the prevalence of hypertension,
      to perform screening to increase awareness, and to improve implementation of
      expert guidelines in clinical practice to improve control.

PMID- 22643155
TI  - Assessment of cardiovascular risk in primary health care.
AB  - OBJECTIVE: This study aimed at investigating whether cardiovascular risk factors
      and their impact on total risk estimation differ between men and women. DESIGN:
      Cross-sectional cohort study. SUBJECTS: Finnish cardiovascular risk subjects (n =
      904) without established cardiovascular disease, renal disease, or known
      diabetes. MAIN OUTCOME MEASURES: Ankle-brachial index (ABI), estimated glomerular
      filtration rate (eGFR), oral glucose tolerance test, and total cardiovascular
      risk using SCORE risk charts. RESULTS: According to the SCORE risk charts, 27.0%
      (95% CI 23.1-31.2) of the women and 63.1% (95% CI 58.3-67.7) of the men (p <
      0.001) were classified as high-risk subjects. Of the women classified as low-risk
      subjects according to SCORE, 25% had either subclinical peripheral arterial
      disease or renal insufficiency. CONCLUSIONS: The SCORE system does not take into
      account cardiovascular risk factors typical in women, and thus underestimates
      their total cardiovascular risk. Measurement of ABI and eGFR in primary care
      might improve cardiovascular risk assessment. especially in women.

PMID- 22643156
TI  - Factors associated with undiagnosed obstructive sleep apnoea in hypertensive
      primary care patients.
AB  - OBJECTIVE: In hypertensive primary care patients below 65 years of age, (i) to
      describe the occurrence of undiagnosed obstructive sleep apnoea (OSA), and (ii)
      to identify the determinants of moderate/severe OSA. DESIGN: Cross-sectional.
      SETTING: Four primary care health centres in Sweden. PATIENTS: 411 consecutive
      patients (52% women), mean age 57.9 years (SD 5.9 years), with diagnosed and
      treated hypertension (BP >140/90). MAIN OUTCOME MEASURES: Occurrence of OSA as
      measured by the apnoea hypopnoea index (AHI). RESULTS: Mild (AHI 5-14.9/h) and
      moderate/severe (AHI > 15/h) OSA were seen among 29% and 30% of the patients,
      respectively. Comparing those without OSA with those with mild or moderate/severe
      OSA, no differences were found in blood pressure, pharmacological treatment (anti
      hypertensive, anti-depressive, and hypnotics), sleep, insomnia symptoms, daytime
      sleepiness, or depressive symptoms. Obesity (BMI > 30 kg/m2) was seen in 30% and
      68% of the patients with mild and moderate/severe OSA, respectively. Male gender,
      BMI > 30 kg/m2, snoring, witnessed apnoeas, and sleep duration >8 hours were
      determinants of obstructive sleep apnoea. CONCLUSION: Previously undiagnosed OSA
      is common among patients with hypertension in primary care. Obesity, snoring,
      witnessed apnoeas, long sleep duration, and male gender were the best predictors
      of OSA, even in the absence of daytime sleepiness and depressive symptoms.

PMID- 22643157
TI  - The course of mental health problems in children presenting with abdominal pain
      in general practice.
AB  - OBJECTIVE: To investigate the course of mental health problems in children
      presenting to general practice with abdominal pain and to evaluate the extent to
      which abdominal pain characteristics during follow-up predict the presence of
      mental health problems at 12 months' follow-up. DESIGN: A prospective cohort
      study with one-year follow-up. SETTING: 53 general practices in the Netherlands,
      between May 2004 and March 2006. SUBJECTS: 281 children aged 4-17 years. MAIN
      OUTCOME MEASURES: The presence of a depressive problem, an anxiety problem, and
      multiple non-specific somatic symptoms at follow-up and odds ratios of duration,
      frequency, and severity of abdominal pain with these mental health problems at
      follow-up. RESULTS: A depressive problem persisted in 24/74 children (32.9%; 95%
      CI 22.3-44.9%), an anxiety problem in 13/43 (30.2%; 95% CI 17.2-46.1%) and the
      presence of multiple non-specific somatic symptoms in 75/170 children (44.1%; 95%
      CI 36.7-51.6%). None of the abdominal pain characteristics predicted a depressive
      or an anxiety problem at 12 months' follow-up. More moments of moderate to severe
      abdominal pain predicted the presence of multiple non-specific somatic symptoms
      at follow-up. CONCLUSIONS: In one-third of the children presenting to general
      practice for abdominal pain, anxiety and depressive problems persist during one
      year of follow-up. Characteristics of the abdominal pain during the follow-up
      period do not predict anxiety or depressive problems after one-year follow-up. We
      recommend following over time children seen in primary care with abdominal pain.

PMID- 22643159
TI  - A new immunoprecipitation-real time quantitative PCR assay for anti-Th/To and
      anti-U3RNP antibody detection in systemic sclerosis.
AB  - INTRODUCTION: Classic anti-nucleolar antibodies anti-Th/To and U3
      ribonucleoprotein (-U3RNP) can help in the diagnosis, prediction of organ
      involvement and prognosis in systemic sclerosis (SSc); however, no validated
      commercial assay is available. We aimed at establishing a novel quantitative real
      time PCR (qPCR) method to detect these antibodies. METHODS: Standard
      immunoprecipitation (IP) was performed using K562 cell extract and RNA components
      were extracted. cDNA was reverse transcribed from RNA components and Th RNA and
      U3 RNA were detected by qPCR using custom primers. Cycle threshold (Ct) values
      were compared in a titration experiment to determine the assay efficacy. The new
      assay was evaluated by testing 22 anti-Th/To and 12 anti-U3RNP positive samples
      in addition to 88 controls, and the results were compared with IP as a gold
      standard. RESULTS: By testing serial 1:8 dilutions of cell lysate as the
      substrate in the IP step, RNA extracted after IP, and its derived cDNA, linear
      dose response curves were noted for both anti-Th/To and -U3RNP. With every
      dilution, Ct values changed approximately three as expected, reflecting the eight
      fold difference of cDNA. The Ct difference between positive and negative samples
      was 8 to 13, which was similar throughout the dilutions. In the specificity
      analysis, the Ct values of positive samples were clearly different from the
      negative groups and the results by qPCR had a near perfect correlation with IP.
      CONCLUSIONS: Our new method readily detects these two clinically important
      antibodies in SSc. Making tests for anti-Th/To and -U3RNP antibodies widely
      available to clinicians should be helpful in the diagnosis and follow-up of SSc
      patients.

PMID- 22643160
TI  - The effects of exercise during pregnancy on the newborn's brain: study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: It is generally accepted that an active lifestyle is beneficial for
      cognition in children, adults and the elderly. Recently, studies using the rat
      animal model found that the pups of mothers who exercised during pregnancy had
      increased hippocampal neurogenesis and better memory and learning abilities. The
      aim of this report is to present the experimental protocol of a study that is
      designed to verify if an active lifestyle during pregnancy in humans has an
      impact on the newborn's brain. METHODS: 60 pregnant women will be included in a
      randomized controlled study. The experimental group will be asked to exercise a
      minimum of 20 minutes three times per week, at a minimal intensity of 55% of
      their maximal aerobic capacity. The control group will not be exercising. The
      effect of exercise during pregnancy on the newborn's brain will be investigated 8
      to 12 days postpartum by means of the mismatch negativity, a neurophysiological
      brain potential that is associated to auditory sensory memory. We hypothesize
      that children born to mothers who exercised during their pregnancy will present
      shorter latencies and larger mismatch negativity amplitudes, indicating more
      efficient auditory memory processes. DISCUSSION: As of September 2011, 17 women
      have joined the study. Preliminary results show that the experimental group are
      active 3.1 +/- 0.9 days per week while the control group only exercise 0.8 +/-
      0.6 days per week. The results of this study will present insight on fetal
      neuroplasticity and will be a valuable tool for health professionals who wish to
      encourage pregnant women to exercise. TRIAL REGISTRATION: ClinicalTrials.gov
      registration: NTC01220778.

PMID- 22643161
TI  - Scoring models of a diet quality index and the predictive capability of mortality
      in a population-based cohort of Swedish men and women.
AB  - OBJECTIVE: To examine how different scoring models for a diet quality index
      influence associations with mortality outcomes. DESIGN: A study within the Malmo
      Diet and Cancer cohort. Food and nutrient intakes were estimated using a diet
      history method. The index included six components: SFA, PUFA, fish and shellfish,
      fibre, fruit and vegetables, and sucrose. Component scores were assigned using
      predefined (based on dietary recommendations) and population-based cut-offs
      (based on median or quintile intakes). Multivariate Cox regression was used to
      model associations between index scores (low, medium, high) and all-cause and
      cause-specific mortality by sex. SETTING: Malmo, the third largest city in
      Sweden. SUBJECTS: Men (n 6940) and women (n 10,186) aged 44-73 years. During a
      mean follow-up of 14.2 years, 2450 deaths occurred, 1221 from cancer and 709 from
      CVD. RESULTS: The predictive capability of the index for mortality outcomes
      varied with type of scoring model and by sex. Stronger associations were seen
      among men using predefined cut-offs. In contrast, the quintile-based scoring
      model showed greater predictability for mortality outcomes among women. The
      scoring model using median-based cut-offs showed low predictability for mortality
      among both men and women. CONCLUSIONS: The scoring model used for dietary indices
      may have a significant impact on observed associations with disease outcomes. The
      rationale for selection of scoring model should be included in studies
      investigating the association between dietary indices and disease. Adherence to
      the current dietary recommendations was in the present study associated with
      decreased risk of all-cause and cause-specific mortality, particularly among men.

PMID- 22643162
TI  - Utilization of hepatitis C antibody-positive livers: genotype dominance is
      virally determined.
AB  - Because of the unrelenting donor shortage, utilization of all potential liver
      donors is essential. However, when utilizing marginal donors it is critical to
      precisely characterize the risks, inform recipients of those risks, and allocate
      these higher risk organs to appropriate candidates. Towards this goal, we need to
      determine the safety and potential consequences, if any, of utilizing hepatitis C
      (HCV) antibody-positive donors in HCV infected recipients. To further
      characterize HCV antibody-positive donors, we analyzed prospectively collected
      serum samples from HCV antibody-positive donors transplanted into HCV RNA
      positive recipients from 5/1993 to 10/2008 for HCV viral load (Roche Cobas
      AmpliPrep/Cobas Taqman HCV Assay) and genotype (Siemens Versant 2.0 LiPA HCV 5'
      UTR/Core Assay). Seventeen of 32 (53%) HCV antibody-positive donors were RNA
      negative. Fifteen patients received an HCV RNA-positive donor and nine donor
      recipient pairs had different genotypes or subtypes for analysis. When genotype 1
      competed with a non-1 genotype, it was found in 5/6 recipients. In 2/3 cases of
      mismatched genotype 1 subtypes, genotype 1a dominated. Kaplan-Meier analysis of
      patient and graft survival and fibrosis progression did not reveal differences
      between patients who received an HCV antibody-positive donor that was viremic or
      aviremic. In conclusion, approximately half of HCV antibody-positive donors were
      aviremic. Viral dominance in viremic donor-recipient pairs seems virally
      determined.

PMID- 22643164
TI  - Functional analysis of concealment: a novel application of prospect and refuge
      theory.
AB  - According to prospect-refuge theory, humans prefer environments that afford
      protection from threat (refuge), but also provide large fields of view
      (prospect). Prospect-refuge theory in the past has traditionally only been
      applied to humans, but many of the same contingencies governing spatial
      preference ought to also hold true in animals. The focus of this study was to
      examine if this phenomena also occurs in animals. Gerbils were placed in an arena
      containing three dome shaped refuges that varied in prospect-refuge levels. A
      simulated predator was released during the trial to examine how contextual
      factors may influence the degree of prospect and refuge preferred. The results
      indicate a preference for the enclosed refuge at stimulus onset even though this
      was not reflective of what happened prior to predator release. The results
      suggest spatial preferences in animals are influenced by prospect-refuge
      considerations in certain contexts.

PMID- 22643163
TI  - Stimulus concordance and risk-assessment in hermit crabs (Coenobita clypeatus):
      implications for attention.
AB  - Recent research has demonstrated that the topography of defensive reactions
      depends on factors that are extraneous to the stimulus that elicits the defensive
      response. For example, hermit crabs will withdraw more slowly to the approach of
      a simulated visual predator (i.e., the eliciting stimulus) when in the presence
      of a coincident acoustic stimulus. Multiple properties related to the magnitude
      (e.g., duration, amplitude) of the acoustic stimulus have been found to modulate
      the crabs' withdrawal response (Chan et al., 2010b). We demonstrate that the
      proximity in spatial location between a threatening visual stimulus and a
      potentially distracting extraneous auditory stimulus is an important determinant
      of anti-predator behavior in hermit crabs. We suggest that a distal relationship
      between the eliciting stimulus and an unrelated signal may produce greater
      distraction. This marks the first reported experimental evidence of this
      relationship in an invertebrate species.

PMID- 22643165
TI  - Children, adolescents, and the media: health effects.
AB  - The media can be a powerful teacher of children and adolescents and have a
      profound impact on their health. The media are not the leading cause of any major
      health problem in the United States, but they do contribute to a variety of
      pediatric and adolescent health problems. Given that children and teens spend >7
      hours a day with media, one would think that adult society would recognize its
      impact on young people's attitudes and behaviors. Too little has been done to
      protect children and adolescents from harmful media effects and to maximize the
      powerfully prosocial aspects of modern media.

PMID- 22643166
TI  - Overview: new media.
AB  - Pediatricians care for children's growth and development from the time they are
      born until they become adults. In addition, pediatricians must be vigilant for
      external influences. Technology influences children of all ages. Seventy-five
      percent of teenagers own cell phones, with 25% using them for social media.
      Technology can lead to an increase in skills and social benefits but there is
      also the potential for harm such as sexting, cyberbullying, privacy issues, and
      Internet addiction, all of which can affect health. Pediatricians must become
      well versed in the new media to provide media-oriented anticipatory guidance and
      advice on media-related issues.

PMID- 22643167
TI  - Social networking sites and adolescent health.
AB  - Social networking sites are popular among and consistently used by adolescents.
      These sites present benefits as well as risks to adolescent health. Recently,
      pediatric providers have also considered the benefits and risks of using social
      networking sites in their own practices.

PMID- 22643168
TI  - Should babies be watching television and DVDs?
AB  - Should babies be watching television and DVDs? This is a reasonable question to
      ask but a difficult one to answer. This article reviews the theories and related
      research to examine what is known about infant media use. The review provides
      evidence both for and against each theory. The importance of infants learning how
      to watch and learn from screen media presentations is indicated and the new world
      of media to which babies are exposed is discussed.

PMID- 22643169
TI  - Internet bullying.
AB  - There is substantial literature on the impact of the mass media on children's and
      adolescents' health and development. The question of what role new technology
      plays in the media's influence is now a subject of both review and discussion,
      particularly regarding health risks and intervention. This article takes a brief
      look at online usage and the theoretical mechanisms that might make Internet
      access more problematic in terms of risks, compared with more traditional media
      such as television and film. One of these risks, known today as cyberbullying or
      Internet harassment, is scrutinized in detail.

PMID- 22643170
TI  - Prosocial effects of media.
AB  - Parents, teachers, health care providers, and other caring adults worry about the
      harmful influence of media messages and images on children and teens and wonder
      how to recognize and encourage positive and healthy use of media. For decades,
      experts have commented on the power of media. Media depictions can lead to
      negative attitudes and behavior in some young viewers. This article discusses
      whether prosocial, tolerant, and cooperative attitudes and behavior can be
      learned and imitated by children and adolescents and whether media can nurture or
      stimulate creativity or actively promote health and well-being in young
      consumers.

PMID- 22643171
TI  - Video games: good, bad, or other?
AB  - Video games are a pervasive pastime among children and adolescents. The growing
      popularity of video games has instigated a debate among parents, researchers,
      video game producers, and policymakers concerning potential harmful and helpful
      effects of video games on children. This article provides an overview of research
      findings on the positive and negative effects of video games, thus providing an
      empirical answer to the question, are video games good or bad? The article also
      provides some guidelines to help pediatricians, parents, and other caregivers
      protect children from negative effects and to maximize positive effects of video
      games.

PMID- 22643172
TI  - The new threat of digital marketing.
AB  - Because of their avid use of new media and their increased spending power,
      children and teens have become primary targets of a new "media and marketing
      ecosystem." The digital marketplace is undergoing rapid innovation as new
      technologies and software applications continue to reshape the media landscape
      and user behaviors. The advertising industry, in many instances led by food and
      beverage marketers, is purposefully exploiting the special relationship that
      youth have with new media, as online marketing campaigns create unprecedented
      intimacies between adolescents and the brands and products that now literally
      surround them.

PMID- 22643173
TI  - Childhood obesity and the media.
AB  - This article assesses the role played by media in contributing to the current
      epidemic of childhood obesity. Electronic media use, often referred to as screen
      time, is significantly correlated with child adiposity. Although the causal
      mechanism that accounts for this relationship is unclear, it is well established
      that reducing screen time improves weight status. Media advertising for unhealthy
      foods contributes to obesity by influencing children's food preferences,
      requests, and diet. Industry efforts have failed to improve the nutritional
      quality of foods marketed on television to children, leading public health
      advocates to recommend government restrictions on child-targeted advertisements
      for unhealthy foods.

PMID- 22643174
TI  - Body image, eating disorders, and the relationship to adolescent media use.
AB  - Historically and currently, media messages around body shape and size emphasize
      the importance of being below-average weight for women and hypermuscular for men.
      The media messages around physical appearance are not realistic for most and lead
      to body dissatisfaction for most adolescents. Interventions designed to mitigate
      the influence of negative media messages on adolescents' body image are
      presented; however, most have shown limited success.

PMID- 22643175
TI  - School daze: why are teachers and schools missing the boat on media?
AB  - Most American schools are 50 years behind in incorporating new technology into
      the classroom and using media wisely. Some experts estimate that 65% of today's
      grade-school students may end up doing jobs that have not even been invented yet.
      Abundant evidence now exists that children and teens learn preferentially from
      the media, yet the media are often frowned on as too distracting for students or
      too distant from the basic 3 Rs. American schools are failing in their
      fundamental responsibility to students. Educators need to learn how to use media
      and new technology wisely.

PMID- 22643176
TI  - Ten years of TeenHealthFX.com: a case study of an adolescent health Web site.
AB  - The Internet, in contrast to in-person interactions with health providers, allows
      anonymous and nonpunitive ease of access. Adolescents have long sought honest,
      direct answers to important but embarrassing questions about health; emerging
      technologies provide a venue to obtain relevant information without geographic,
      time, financial, and personal barriers. This article is a case study of
      TeenHealthFX.com. Those interested in how youth access online health information
      can learn of the positive and negative aspects of delivering messages through the
      Internet. This article discusses the process involved in creating and maintaining
      TeenHealthFX and the challenges of providing online health information to
      adolescents via new technology.

PMID- 22643177
TI  - Preface. Children, adolescents, and the media.

PMID- 22643178
TI  - A novel missense mutation in the signal peptide of the human POMC gene: a
      possible additional link between early-onset type 2 diabetes and obesity.
AB  - Rare mutations in several genes have a critical role in the control of
      homeostatic mechanisms such as food-intake, energy balance and glucose
      metabolism. In this study, we performed a mutational screening in a 58-year-old
      woman presenting early-onset type 2 diabetes and central obesity. The entire
      coding regions of MC4R, MC3R, HNF1A, GCK and POMC (pro-opiomelanocortin) genes
      were analyzed by direct sequencing. A new missense mutation was identified within
      the POMC gene signal peptide sequence, resulting in a heterozygous substitution
      of an arginine for a glycine at codon 15 (p.A15G) that was excluded in 300
      healthy normal weight controls. The mutation segregated in the family and was
      associated with overweight, type 2 diabetes, hypertension and coronary heart
      disease in the carriers. Functional studies demonstrated that POMC protein was
      not detectable in beta-TC3 cells transfected with A15G-POMC vector as well as in
      their culture media, despite POMC mRNA levels were comparable for amount and
      stability to those of wild-type-transfected cells. In silico RNA folding
      prediction indicated that the mutation gives rise to a different RNA secondary
      structure, suggesting that it might affect translation and protein synthesis. To
      the best of our knowledge, this is the first report addressing the functional
      consequences of a mutation in the signal peptide of POMC. These findings further
      support the hypothesis that POMC-derived peptides might have a role in the
      control of peripheral glucose metabolism and suggest that disruption of central
      POMC secretion might represent an additional link between type 2 diabetes and
      obesity.

PMID- 22643179
TI  - Meta-analysis of genetic association studies under heterogeneity.
AB  - In multi-cohort genetic association studies or meta-analysis, associations of
      genetic variants with complex traits across cohorts may be heterogeneous because
      of genuine genetic diversity or differential biases or errors. To detect the
      associations of genes with heterogeneous associations across cohorts, new global
      fixed-effect (FE) and random-effects (RE) meta-analytic methods have been
      recently proposed. These global methods had improved power over both traditional
      FE and RE methods under heterogeneity in limited simulation scenarios and data
      application, but their usefulness in a wide range of practical situations is not
      clear. We assessed the performance of these methods for both binary and
      quantitative traits in extensive simulations and applied them to a multi-cohort
      association study. We found that these new approaches have higher power to detect
      mostly the very small to small associations of common genetic variants when
      associations are highly heterogeneous across cohorts. They worked well when both
      the underlying and assumed genetic models are either multiplicative or dominant.
      But, they offered no clear advantage for less common variants unless
      heterogeneity was substantial. In conclusion, these new meta-analytic methods can
      be used to detect the association of genetic variants with high heterogeneity,
      which can then be subjected to further exploration, in multi-cohort association
      studies and meta-analyses.

PMID- 22643180
TI  - Analytical and simulation methods for estimating the potential predictive ability
      of genetic profiling: a comparison of methods and results.
AB  - Various modeling methods have been proposed to estimate the potential predictive
      ability of polygenic risk variants that predispose to various common diseases.
      However, it is unknown whether differences between them affect their conclusions
      on predictive ability. We reviewed input parameters, assumptions and output of
      the five most common methods and compared their estimates of the area under the
      receiver operating characteristic (ROC) curve (AUC) using hypothetical data
      representing effect sizes and frequencies of genetic variants, population disease
      risk and number of variants. To assess the accuracy of the estimated AUCs, we
      aimed to reproduce the AUCs of published empirical studies. All methods assumed
      that the combined effect of genetic variants on disease risk followed a
      multiplicative risk model of independent genetic effects, but they either assumed
      per allele, per genotype or dominant/recessive effects for the genetic variants.
      Modeling strategy and input parameters differed. Methods used simulation analysis
      or analytical formulas with effect sizes quantified by odds ratios (ORs) or
      relative risks. Estimated AUC values were similar for lower ORs (<1.2). When AUCs
      were larger (>0.7) due to variants with strong effects, differences in estimated
      AUCs between methods increased. The simulation methods accurately reproduced the
      AUC values of empirical studies, but the analytical methods did not. We conclude
      that despite differences in input parameters, the modeling methods estimate
      similar AUC for realistic values of the ORs. When one or more variants have
      stronger effects and AUC values are higher, the simulation methods tend to be
      more accurate.

PMID- 22643182
TI  - Back to the embryonic stage: Nodal as a biomarker for breast cancer progression.
AB  - The embryonic morphogen Nodal, a member of the transforming growth factor-beta
      superfamily, is not expressed in the majority of normal adult tissues. However, a
      growing body of evidence indicates that Nodal expression re-emerges in a number
      of human cancers, including melanoma, glioma, endometrial, and prostate cancers.
      Reactivation of Nodal signaling in these tumors contributes to their
      aggressiveness. Strizzi and colleagues, in a paper published in this issue of
      Breast Cancer Research, investigate the clinical significance of Nodal expression
      in breast cancer. They report that Nodal expression is significantly greater in
      malignant versus benign breast disease. More importantly, Nodal levels correlated
      with grading, staging, and lymph node involvement, independent of the estrogen
      receptor/progesterone receptor or HER2 status. Collectively, these data suggest
      that Nodal could serve as a potential biomarker for invasive disease and a
      potential therapeutic target in breast cancer.

PMID- 22643181
TI  - Best practice guidelines and recommendations on the molecular diagnosis of
      myotonic dystrophy types 1 and 2.
AB  - Myotonic dystrophy is an autosomal dominant, multisystem disorder that is
      characterized by myotonic myopathy. The symptoms and severity of myotonic
      dystrophy type l (DM1) ranges from severe and congenital forms, which frequently
      result in death because of respiratory deficiency, through to late-onset baldness
      and cataract. In adult patients, cardiac conduction abnormalities may occur and
      cause a shorter life span. In subsequent generations, the symptoms in DM1 may
      present at an earlier age and have a more severe course (anticipation). In
      myotonic dystrophy type 2 (DM2), no anticipation is described, but cardiac
      conduction abnormalities as in DM1 are observed and patients with DM2
      additionally have muscle pain and stiffness. Both DM1 and DM2 are caused by
      unstable DNA repeats in untranslated regions of different genes: A (CTG)n repeat
      in the 3'-UTR of the DMPK gene and a (CCTG)n repeat in intron 1 of the CNBP
      (formerly ZNF9) gene, respectively. The length of the (CTG)n repeat expansion in
      DM1 correlates with disease severity and age of onset. Nevertheless, these repeat
      sizes have limited predictive values on individual bases. Because of the disease
      characteristics in DM1 and DM2, appropriate molecular testing and reporting is
      very important for the optimal counseling in myotonic dystrophy. Here, we
      describe best practice guidelines for clinical molecular genetic analysis and
      reporting in DM1 and DM2, including presymptomatic and prenatal testing.

PMID- 22643183
TI  - Clinical evaluation of repeat percutaneous vertebroplasty for symptomatic
      cemented vertebrae.
AB  - BACKGROUND: Percutaneous vertebroplasty (PV) with polymethylmethacrylate is
      widely used to treat osteoporotic vertebral compression fracture and satisfactory
      clinical outcomes have been reported in the literature. However, recurrent or
      persistent back pain after PV is not uncommon. Sometimes, the pain may result
      from pathogenesis within the previously treated vertebra. In this study, we
      evaluated the efficacy and safety of repeat PV for treating patients with
      recurrent back pain caused by the previously cemented vertebrae. METHODS: We
      retrospectively reviewed the medical records of 18 patients who underwent repeat
      PV to treat symptomatic cemented vertebrae. Patients were categorized into 3
      groups based on clinical presentation and imaging studies: those with refracture
      (RF), residual vacuum (RV), and osteonecrosis (ON) along the bone-cement
      interface. A bipedicle approach was used for repeat PV in all patients. The
      visual analogue scale (VAS) and modified Brodsky criteria were used to evaluate
      clinical outcomes before and after surgery. The Kruskal-Wallis test, Wilcoxon
      signed-rank test, and Spearman correlation analyses were used to analyze patient
      surgical prognosis and radiologic findings. RESULTS: Nine patients were diagnosed
      with RF, 5 with RV, and 4 with ON. The average VAS score was 77.1 (range, 62-90)
      before repeat PV (80.1, 72.4, and 76.3 for the RF, RV, and ON groups,
      respectively) and 34.4 (range, 25-45) after repeat PV treatment (33.1, 36.8, and
      34.3 for the RF, RV, and ON groups, respectively). The VAS score significantly
      decreased in all 3 groups. The vertebral body height was significantly restored
      by a mean of 13.9% across all groups (17.8%, 12.7%, and 6.8% in the RF, RV, and
      ON groups, respectively). Fifteen patients recovered from vertebral compression
      fracture and regained their preinjury activities of daily living. No surgery
      related complications occurred except asymptomatic cement leakage in 5 patients.
      CONCLUSIONS: The results of this research demonstrate that repeat PV may be an
      effective method for relieving recurrent or persistent pain in patients with
      symptomatic cemented vertebrae, allowing them to regain functional activity.

PMID- 22643184
TI  - Spine Bull's-Eye Robot guidewire placement with pedicle standard axis view for
      thoracic and lumbar pedicle screw fixation.
AB  - STUDY DESIGN: Prospective. OBJECTIVE: To explore the feasibility and accuracy of
      thoracic and lumbar pedicle guidewire placement using a newly developed Spine
      Bull's-Eye Robot with the pedicle standard axis view (PSAV). SUMMARY OF
      BACKGROUND DATA: Placement of pedicle screws in the thoracic spine is considered
      to be particularly risky surgery and is associated with a relatively high rate of
      screw misplacement. Use of robot-assisted surgery may improve the accuracy of
      pedicle screw placement. METHODS: The study included 204 pedicles (T1-L5) from 6
      human vertebrae and 5 pedicles from 3 patients. Computed tomographic
      reconstruction of target vertebrae was performed for surgical planning. Using the
      PSAV, a guidewire (1.2 mm diameter, 13.5 cm length) was inserted into the "bull's
      eye" (the center of the pedicle circular projection) using the remotely operated
      Spine Bull's-Eye Robot. After surgery, vertebral body axial and lateral
      radiographs, and computed tomographic scans were used to assess the guidewire
      trajectory. Planned and actual (postoperative) measures for transverse section
      angle, sagittal section angle, and the superior/inferior and medial/lateral
      vertical distances from the entry point were compared. RESULTS: The PSAV was
      acquired clearly in 203 of 209 (97.1%) pedicles; the guidewire was successfully
      inserted in each of these pedicles. There were no significant differences between
      any of the planned and actual (postoperative) measures. All of the pedicles for
      which guidewire placement was abandoned (because of lack of bull's-eye resolution
      in the PSAV) were small upper thoracic specimens, exhibiting evidence of
      decalcification, presumably because of preservation procedures. None of the
      patients experienced complications associated with guidewire placement.
      CONCLUSIONS: Use of the Spine Bull's-Eye Robot with PSAV seems be an accurate and
      feasible approach for guidewire (and thus pedicle screw) placement in the
      thoracic and lumbar spine.

PMID- 22643185
TI  - Radiographic analysis of PEEK cage and FRA in adult spinal deformity fused to
      sacrum.
AB  - STUDY DESIGN: Retrospective radiographic study. OBJECTIVE: To radiographically
      evaluate sagittal plane profile and fusion rates of polyetheretherketone (PEEK)
      cages versus femoral ring allografts (FRAs) in patients with adult spinal
      deformity fused to the sacrum. SUMMARY OF BACKGROUND DATA: FRAs have been widely
      used in various degenerative lumbar spine disorders and in adult deformity to
      achieve interbody fusions with promising results. PEEK cages have gained
      increasing popularity of late; however, there is little documentation to the
      radiographic comparisons between PEEK cages and FRAs used in patients with adult
      spine deformity treated with long fusions to the sacrum. METHODS: From March 2006
      to February 2010, we analyzed 48 patients (mean age, 56.3+/-13.9 y) of 61
      consecutive adult patients with global coronal and sagittal adult spine
      deformities who underwent first stage ALIF using PEEK cages or FRAs at L4-L5, L5
      S1 segments followed by long (>6 levels) posterior instrumentation. PEEK cages
      and FRAs were used randomly according to surgeon's preference. Two independent
      observers retrospectively evaluated preoperative and postoperative disk height,
      foraminal height, segmental lordosis, and the interbody fusion rates at different
      postoperative intervals. RESULTS: Both PEEK cages and FRAs significantly (P<0.05)
      maintained disk space height at all follow-up times. PEEK cages maintained
      foraminal height and segmental lordosis, especially at L4-L5 better than FRAs at
      the final follow-up. At the final follow-up, PEEK cages achieved 94.9% of fusion
      rate, which was significantly (P<0.05) superior to FRA (84.2%), and PEEK cages
      were superior to FRAs in attaining earlier solid fusion. The Prolo functional
      scores of FRAs or/and PEEK cages were significantly improved at the final follow
      up and did not show a significant difference between them. CONCLUSIONS: Both PEEK
      cages and FRAs can significantly increase disk space height and achieve similar
      clinical outcomes in treating adult spinal deformity fused to the sacrum. The
      radiographic results of PEEK cages were superior to FRAs in terms of an earlier
      solid fusion, and greater restoration of segmental lordosis.

PMID- 22643186
TI  - Sternocleidomastoid muscular flap: treatment of persistent cerebrospinal fluid
      leak after anterior cervical spine surgery.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To describe a novel application of
      rotational sternocleidomastoid (SCM) muscle flap in management of ventral
      cervical durotomy. SUMMARY OF BACKGROUND DATA: Even for the most experienced
      surgeons, incidental durotomy is a common occurrence in spine surgery. Primary
      direct suture repair is indicated to avoid possible complications such as
      pseudomeningocele or spinocutaneous fistula formation. Significant secondary
      effects of these complications have been described, including airway compromise,
      radiculopathy, myelopathy, and infection. When primary repair is not feasible,
      surgeons have used alternative management techniques based on their clinical
      judgment. In the setting of persistent symptomatic cerebrospinal fluid leak after
      repair, reoperation is warranted. METHODS: A retrospective review was conducted
      of clinical records and radiographic data for 2 patients who underwent
      reoperation for management of ventral cervical durotomy encountered during
      anterior cervical spine surgery. SCM muscular flap was used to augment durotomy
      repair. RESULTS: Both patients did not have any persistent cerebrospinal fluid
      leak after repair with pedicled SCM muscle flap, and did not require any further
      surgical procedures related to the cervical spine. CONCLUSIONS: The use of a
      rotational SCM muscular flap may be useful in cases of ventral cervical durotomy
      refractory to conventional management.

PMID- 22643187
TI  - Two-year follow-up after decompressive surgery with and without implantation of
      an interspinous device for lumbar spinal stenosis: a prospective controlled
      study.
AB  - STUDY DESIGN: Two-arm prospective controlled study. OBJECTIVE: The aim of our
      study was to prospectively assess the outcome of symptomatic lumbar spinal
      stenosis (LSS) treated with decompressive surgery alone in comparison with
      additional implantation of the Coflex interspinous device. SUMMARY OF BACKROUND
      DATA: In symptomatic LSS, decompression surgery is an established treatment.
      Recently, a number of interspinous devices have been introduced as an alternative
      to conventional surgical procedures. The theoretical aim of the Coflex device is
      to unload the facet joints, restore foraminal height, and provide stability to
      improve the clinical outcome. Published information is limited, and there are no
      data that prove the superiority of the implant in comparison with traditional
      surgical approaches. METHODS: Sixty-two patients with symptomatic LSS were
      treated with decompressive surgery; 31 of these patients received an additional
      Coflex device. Preoperatively and postoperatively, disability and pain scores
      were measured using the Oswestry Disability Index, the Roland-Morris Disability
      Questionnaire, the Visual Analog Scale, and the pain-free walking distance.
      Patients underwent postoperative assessments at 3, 6, 12, and 24 month including
      the above-mentioned scores and patient satisfaction. RESULTS: There was a
      significant improvement (P<0.001) in the clinical outcome assessed in the
      Oswestry Disability Index, the Roland-Morris Disability Questionnaire, the Visual
      Analog Scale, and the pain-free walking distance at all times of reinvestigation
      compared with the base line in both groups. Up to 2 years after surgery, there
      were no significant differences between both groups in all ascertained
      parameters, including the patient satisfaction and subjective operation decision.
      CONCLUSIONS: The results of this first prospective controlled study indicate that
      the additional placement of a Coflex interspinous device does not improve the
      already good clinical outcome after decompressive surgery for LSS in the 24-month
      follow-up interval.

PMID- 22643188
TI  - A decade of palliative & supportive care.

PMID- 22643189
TI  - Decontamination of cephalosporin-resistant Enterobacteriaceae during selective
      digestive tract decontamination in intensive care units.
AB  - OBJECTIVES: Prevalences of cephalosporin-resistant Enterobacteriaceae are
      increasing globally, especially in intensive care units (ICUs). The effect of
      selective digestive tract decontamination (SDD) on the eradication of
      cephalosporin-resistant Enterobacteriaceae from the intestinal tract is unknown.
      We quantified eradication rates of cephalosporin-resistant and cephalosporin
      susceptible Enterobacteriaceae during SDD in patients participating in a 13
      centre cluster-randomized study and from a single-centre cohort. METHODS: All SDD
      patients colonized with Enterobacteriaceae in the intestinal tract at ICU
      admission were included. Cephalosporin resistance was defined as resistance to
      ceftazidime, cefotaxime or ceftriaxone and aminoglycoside resistance as
      resistance to tobramycin or gentamicin. Duration of rectal colonization was
      determined by screening twice weekly during ICU stay. Swabs were inoculated on
      selective medium supplemented with tobramycin or cefotaxime. RESULTS: Five
      hundred and seven (17%) of 2959 SDD patients with at least one rectal sample were
      colonized with Enterobacteriaceae at ICU admission: 77 (15%) with cephalosporin
      resistant Enterobacteriaceae and 50 (10%) with aminoglycoside-resistant
      Enterobacteriaceae. Fifty-six (73%) patients colonized with cephalosporin
      resistant Enterobacteriaceae were successfully decontaminated before ICU
      discharge, as were 343 (80%) patients colonized with cephalosporin-susceptible
      Enterobacteriaceae (P = 0.17). For aminoglycoside resistance, 31 (62%) patients
      were decontaminated, as were 368 patients (81%) colonized with aminoglycoside
      susceptible Enterobacteriaceae (P < 0.01). On average, decolonization was
      demonstrated after 4 days if colonized with cephalosporin-susceptible
      Enterobacteriaceae and aminoglycoside-susceptible Enterobacteriaceae, and after 5
      and 5.5 days if colonized with cephalosporin-resistant Enterobacteriaceae and
      aminoglycoside-resistant Enterobacteriaceae, respectively (log-rank test P =
      0.053 for cephalosporin resistance and P = 0.03 for aminoglycoside resistance).
      If eradication failed, no associations were found with increased resistance in
      time (P > 0.05 for all comparisons). CONCLUSIONS: SDD can successfully eradicate
      cephalosporin-resistant Enterobacteriaceae from the intestinal tract.

PMID- 22643190
TI  - Persistent low-level HIV-1 RNA between 20 and 50 copies/mL in antiretroviral
      treated patients: associated factors and virological outcome.
AB  - OBJECTIVES: The aim of our study was to identify factors associated with
      persistent low-level viraemia (LLV) in HIV-infected patients under suppressive
      antiretroviral therapy and to assess the virological outcome of these patients.
      METHODS: LLV was defined as at least two HIV-1 RNA values between 20 and 50
      copies/mL during 1 year of follow-up. We compared patients with all values <20
      copies/mL (LLV-) and patients with LLV (LLV+). The 'blip ratio' was defined as
      (number of HIV-1 RNA values >50 copies/mL)/(number of HIV-1 RNA determinations)
      before study inclusion. RESULTS: Among the 656 patients included, 5.8% were in
      group LLV+. CDC stage B/C at study inclusion and a higher blip ratio before the
      study period were the only factors independently associated with LLV. During the
      1 year follow-up, the proportion of patients experiencing virological failure was
      not different between the LLV- and LLV+ groups, and 40% of patients shifted from
      LLV+ to LLV- status. CONCLUSIONS: LLV was infrequent in our series and the follow
      up did not evidence a higher rate of virological failure than in fully suppressed
      patients. LLV seems to be a transient phenomenon that might be driven by residual
      ongoing viral replication and/or viral release and/or accuracy of viral load
      assay at lower values.

PMID- 22643191
TI  - The vanadyl ribonucleoside complex inhibits ribosomal subunit formation in
      Staphylococcus aureus.
AB  - OBJECTIVES: The discovery of new antibiotic targets is important to stem the
      increase in antibiotic resistance to most currently used antimicrobials. The
      bacterial ribosome is a major target for a large number of antibiotics that
      inhibit different aspects of translation. Most of these antimicrobial agents also
      inhibit ribosomal subunit formation as a second cellular target. Precise subunit
      assembly requires the activity of several distinct RNases for proper rRNA
      processing. The present work shows that the vanadyl ribonucleoside complex (VRC)
      inhibited RNases in Staphylococcus aureus involved in ribosomal subunit formation
      without an effect on translation. METHODS: Methicillin-susceptible and -resistant
      strains of S. aureus were examined for the inhibitory effects of VRC on cell
      viability by colony counting. Protein synthesis rates were measured by isotopic
      methionine incorporation. Ribosome synthesis was measured by radiolabelled
      uridine incorporation into ribosomal subunits as displayed on sucrose gradients.
      Pulse and chase radiolabelling was used to measure subunit synthesis rates. RNA
      turnover was determined by a gel on a chip assay. RESULTS: The rates of subunit
      synthesis and the amounts of both subunits were significantly reduced in the
      presence of the compound. Ribosomal RNA was degraded and cell viability was
      reduced as a consequence. VRC also stimulated the inhibitory effects of a
      macrolide and an aminoglycoside antibiotic on ribosome formation. CONCLUSIONS:
      Bacterial ribosomal subunit synthesis was specifically impaired in VRC-treated
      cells, with the rates and amounts of both subunits reduced. Cell viability was
      significantly reduced and rRNA turnover was stimulated.

PMID- 22643192
TI  - Role of stop codons in development and loss of vancomycin non-susceptibility in
      methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVES: Problems of vancomycin non-susceptible Staphylococcus aureus (VISA)
      and subsequent treatment failure are increasing. This study aimed to observe
      development and loss of vancomycin non-susceptibility, determine exposure time
      needed for resistance development, and follow mutations in the VraSR and GraSR
      two-component systems during these processes. METHODS: Sequences of vraS, graR
      and rpoB, proposed as critical sites of mutation associated with non
      susceptibility development, were compared in susceptible clinical methicillin
      resistant S. aureus isolates both initially and following vancomycin induction
      and its withdrawal, to identify mutations. Mutations were correlated with
      exposure time, increase in vancomycin MIC and phenotypic changes. RESULTS: Both
      time required for heterogeneous VISA and VISA development, and maximum MIC
      attained (6-20 mg/L) varied between strains. Sequence analysis revealed the
      presence of stop codons in an initial strain with delayed non-susceptibility
      development. Other changes in vraS and graR occurred during VISA development in
      all isolates. After removal of vancomycin pressure, most strains reverted to
      susceptibility accompanied by emergence of stop codons in both vraS and graR. One
      strain not displaying stop codons remained resistant in the absence of vancomycin
      pressure. A substitution in GraR (D148Q) appeared to be associated with an
      elevated MIC (20 mg/L). No rpoB mutations were observed throughout VISA
      development. CONCLUSIONS: Vancomycin non-susceptibility developed in all strains
      tested. Mutations in vraS and graR appeared to be essential for VISA development,
      with stop codons playing an important role in delaying non-susceptibility
      development and reversion. Absence of mutations in rpoB suggests that these are
      not essential for vancomycin resistance. Further work is required to confirm
      consistent changes involved in non-susceptibility development.

PMID- 22643193
TI  - Hospital costs, length of stay and mortality attributable to invasive
      scedosporiosis in haematology patients.
AB  - BACKGROUND: Scedosporium species are increasingly recognized as a cause of
      invasive mould disease in haematology patients, but little is known about the
      hospitalization costs and outcomes attributable to invasive scedosporiosis
      (SCEDO). METHODS: A retrospective case-control study was undertaken during 2002
      10 to determine the attributable inpatient costs, length of stay (LOS) and
      mortality associated with SCEDO in haematology patients. Case patients with SCEDO
      (n = 30) were matched 1 : 2 to controls (n = 60) according to haematological
      diagnosis, admission year and age. Diagnostics, antifungal drugs, ward and other
      SCEDO-related costs were estimated using actual cost data. Median regression
      modelling was used to adjust for variables that were not accounted for in the
      matched-pairs analysis. RESULTS: The crude total median cost of treating SCEDO
      was AU$32 182 per patient versus AU$17 424 per control. In multivariable
      analysis, SCEDO was associated with median excess costs of AU$23 611 (95% CI =
      AU$17 992-AU$29 231; P < 0.001), approximating US$15 509 at purchasing power
      parity, with prolonged LOS of 13 days (95% CI = 8.2-17.8 days; P < 0.001).
      Exclusion of cases and matched pairs with early death further increased the
      median excess cost and LOS. The cost differential was driven by ward costs (64%,
      P = 0.005) and antifungal treatment costs (29%, P < 0.001). The all-cause
      inpatient mortality was 38 times higher for the SCEDO cases versus the control
      group (63.3% versus 1.7%; P < 0.001). CONCLUSIONS: SCEDO has substantial impact
      on hospital resource consumption, LOS and mortality in haematology patients. Risk
      factors and preventative measures for SCEDO should be further studied.

PMID- 22643194
TI  - Early-onset versus late-onset nonanastomotic biliary strictures post liver
      transplantation: risk factors reflect different pathogenesis.
AB  - Nonanastomotic biliary strictures (NAS) cause significant morbidity post liver
      transplantation. Timing of stricture development varies considerably, but the
      relationship between timing of stricture onset and aetiology has not been fully
      elucidated. Database analysis was performed on all adult patients undergoing
      liver transplantation between 1st January 1990 and 31st May 2008. Diagnosis of
      NAS required demonstration on at least two radiological studies. Early NAS were
      defined as developing <1 year post transplant (minimum 1-year follow-up) and late
      NAS developing >1 year post transplant (minimum 10-year follow-up). Ninety-six of
      397 patients developed NAS (24%); 54 were early-onset NAS (56%) and 42 late-onset
      NAS (44%). Primary sclerosing cholangitis (PSC) was the only risk factor for NAS
      overall (P = 0.001). However, when patients with PSC were excluded, older donor
      age was a significant risk for NAS (P = 0.003). Early-onset NAS were associated
      with advanced donor age (P = 0.02), high MELD score (P = 0.001) and ABO-identical
      grafts (P = 0.02), whereas late-onset NAS were associated with PSC (P = 0.0008),
      bilio-enteric anastomosis (P = 0.006) and tacrolimus (P = 0.0001). Advanced donor
      age is a significant risk for NAS in patients without PSC. Importantly, aetiology
      of NAS varies depending on time to stricture development, suggesting early-onset
      and late-onset NAS may have different pathogenesis.

PMID- 22643195
TI  - Race/ethnic discrimination and preventive service utilization in a sample of
      whites, blacks, Mexicans, and Puerto Ricans.
AB  - BACKGROUND: Race/ethnic discrimination is associated with poorer mental and
      physical health, worse health behaviors, and increased mortality, in addition to
      overall race/ethnic disparities in health. More specifically, it has been
      suggested as a possible determinant of the significant race/ethnic differences in
      the quantity and quality of medical care received by individuals in the United
      States. OBJECTIVES: The current study examines the association between 3 measures
      of racial/ethnic discrimination (Experiences of Discrimination, Everyday
      Discrimination Scale and discrimination in health care) and 6 types of preventive
      services (mammogram, clinical breast examination, Pap smear,
      colonoscopy/sigmoidoscopy, blood pressure screening, and diabetes screening).
      RESEARCH DESIGN: Frequencies and correlations are run within a population-based
      sample of 1699 respondents from Chicago that includes whites, African Americans,
      Mexicans, and Puerto Ricans. Adjusted logistic regression models are run
      separately by race/ethnicity. RESULTS: Findings show that levels of perceived
      discrimination vary between all race/ethnic groups, with blacks consistently
      reporting the highest levels and whites the lowest. Discrimination is only
      inconsistently related to obtaining screenings for cancer, hypertension, and
      diabetes. The few significant relationships found differed both by measure of
      discrimination and the respondents' race and ethnicity. CONCLUSIONS: Given the
      growing diversity in the United States and the prevalence of discrimination, more
      research regarding its impact on health care utilization is needed. Only when all
      the factors influencing patient behaviors are better understood will policies and
      interventions designed to improve them be successful. These are important steps
      that will help attain our national goals of eliminating race/ethnic disparities
      in health.

PMID- 22643196
TI  - Variations in US hospital performance on imaging-use measures.
AB  - BACKGROUND: The Hospital Outpatient Quality Reporting Program (HOQR) publicly
      reports measures of US hospitals' use of 4 imaging studies that may be
      problematic if overused: magnetic resonance imaging (MRI) for low back, follow-up
      imaging after screening mammography, and abdominal and thoracic computed
      tomography (CT) with and without contrast. OBJECTIVES: To characterize
      performance on these measures, determine whether performance was consistent
      across measures, and identify hospital characteristics associated with highest
      decile imaging use. RESEARCH DESIGN: Cross-sectional analysis. MEASUREMENTS:
      Correlation across measures was assessed using Spearman rank order tests. We
      linked 2008 HOQR data to the 2009 American Hospital Association Survey and used
      multivariable logistic regression to examine associations between hospital
      characteristics and the likelihood of highest-decile imaging use. RESULTS:
      Imaging use varied widely. Imaging use was weakly correlated (rho<0.10) across
      most measures. Compared with hospitals with moderate imaging volume (25th to 75th
      percentile), hospitals with low volume (<25th percentile) were more likely to
      report highest-decile imaging use on all measures [adjusted odds ratios (95%
      confidence interval) range from 1.38 (1.05-1.80) for CT Abdomen to 4.22 (3.04
      5.84) for MRI Back]. Rural hospitals were more likely to report highest-decile
      use on most measures [MRI: 1.42 (1.21-1.68), CT Abdomen: 1.46 (1.28-1.66), and CT
      Thorax: 1.32 (1.16-1.51)]. For-profit hospitals were more likely to report
      highest-decile use on mammography [1.47 (1.10-1.98)] and CT Thorax measures [1.71
      (1.28-2.27)]. CONCLUSIONS: Wide variations in imaging use and extraordinarily
      high use at some hospitals may indicate that imaging overuse occurs at US
      hospitals. The effectiveness of the HOQR measures to decrease imaging overuse
      remains to be seen.

PMID- 22643197
TI  - Variation in academic medical centers' coding practices for postoperative
      respiratory complications: implications for the AHRQ postoperative respiratory
      failure Patient Safety Indicator.
AB  - BACKGROUND: The Agency for Healthcare Research and Quality Patient Safety
      Indicator (PSI) 11 uses International Classification of Disease, 9th Clinical
      Modification diagnosis code 518.81 ("Acute respiratory failure")-but not the
      closely related alternative, 518.5 ("Pulmonary insufficiency after trauma and
      surgery")-to detect cases of postoperative respiratory failure. We sought to
      determine whether hospitals vary in the use of 518.81 versus 518.5 and whether
      such variation correlates with coder beliefs. STUDY DESIGN: We conducted a cross
      sectional analysis of administrative data from July 2009 through June 2010 for
      UHC (formerly University HealthSystem Consortium)-affiliated centers to assess
      the use of diagnosis codes 518.81 and 518.5 in PSI 11-eligible cases. We also
      surveyed coders at these centers to evaluate whether variation in the use of
      518.81 versus 518.5 might be linked to coder beliefs. We asked survey respondents
      which diagnosis they would use for 2 ambiguous cases of postoperative pulmonary
      complications and how much they agreed with 6 statements about the coding
      process. RESULTS: UHC-affiliated centers demonstrated wide variation in the use
      of 518.81 and 518.5, ranging from 0 to 26 cases and 0 to 56 cases/1000 PSI 11
      eligible hospitalizations, respectively. Of 56 survey respondents, 64% chose
      518.81 and 30% chose 518.5 for a clinical scenario involving postoperative
      respiratory failure, but these responses were not associated with actual coding
      of 518.81 or 518.5 at the center level. Sixty-two percent of respondents agreed
      that they are constrained by the words that physicians use. Their self-reported
      likelihood of querying physicians to clarify the diagnosis was significantly
      associated with coding of 518.5 at the center level. CONCLUSIONS: The extent to
      which diagnosis code 518.81 is used relative to 518.5 varies considerably across
      centers, based on local coding practice, the specific wording of physician
      documentation, and coder-physician communication. To standardize the coding of
      postoperative respiratory failure, the 518.81 and 518.5 codes have recently been
      revised to make the available options clearer and mutually exclusive, which may
      improve the capacity of PSI 11 to discriminate true differences in quality of
      care.

PMID- 22643198
TI  - The effects of health care benefits on health care use and health: a randomized
      trial for disability insurance beneficiaries.
AB  - BACKGROUND: Under current law, most Social Security Disability Insurance (SSDI)
      beneficiaries are not eligible for Medicare until 29 months after the Social
      Security Administration determines the onset of their disability. During this
      waiting period, >1 in 5 lacks health insurance. This study investigated the
      effects of providing health care benefits on the health, employment, and other
      services of uninsured beneficiaries. METHODS: New SSDI beneficiaries without
      health insurance were randomly assigned to receive health care benefits, health
      care benefits plus additional supports, or a control group. RESULTS: Compared
      with a control group, those provided health care benefits used more health care,
      had fewer unmet medical needs, spent less out of pocket on health care, and
      reported improved health. In addition, those provided the additional supports
      were more likely to look for work, but the supports did not affect work or SSDI
      benefits at this very early period. CONCLUSIONS: The results provide rigorous
      evidence that health care benefits can increase health care use and health
      outcomes. Longer-term follow-up is needed to fully assess the program's effects
      on its ultimate benefits and costs, including its long-term effects on health,
      employment, and benefit receipt.

PMID- 22643200
TI  - The global scope of ENT.

PMID- 22643199
TI  - Performance of claims-based algorithms for identifying heart failure and
      cardiomyopathy among patients diagnosed with breast cancer.
AB  - BACKGROUND: Cardiotoxicity is a known complication of certain breast cancer
      therapies, but rates come from clinical trials with design features that limit
      external validity. The ability to accurately identify cardiotoxicity from
      administrative data would enhance safety information. OBJECTIVE: To characterize
      the performance of clinical coding algorithms for identification of cardiac
      dysfunction in a cancer population. RESEARCH DESIGN: We sampled 400 charts among
      6460 women diagnosed with incident breast cancer, tumor size >= 2 cm or node
      positivity, treated within 8 US health care systems between 1999 and 2007. We
      abstracted medical records for clinical diagnoses of heart failure (HF) and
      cardiomyopathy (CM) or evidence of reduced left ventricular ejection fraction. We
      then assessed the performance of 3 different International Classification of
      Diseases, 9th Edition (ICD-9)-based algorithms. RESULTS: The HF/CM coding
      algorithm designed a priori to balance performance characteristics provided a
      sensitivity of 62% (95% confidence interval, 40%-80%), specificity of 99% (range,
      97% to 99%), positive predictive value (PPV) of 69% (range, 45% to 85%), and
      negative predictive value (NPV) of 98% (range, 96% to 99%). When applied only to
      incident HF/CM (ICD-9 codes and gold standard diagnosis both occurring after
      breast cancer diagnosis) in patients exposed to anthracycline and/or trastuzumab
      therapy, the PPV was 42% (range, 14% to 76%). CONCLUSIONS: Claims-based
      algorithms have moderate sensitivity and high specificity for identifying HF/CM
      among patients with invasive breast cancer. As the prevalence of HF/CM among the
      breast cancer population is low, ICD-9 codes have high NPV but only moderate PPV.
      These findings suggest a significant degree of misclassification due to HF/CM
      overcoding versus incomplete clinical documentation of HF/CM in the medical
      record.

PMID- 22643201
TI  - Establishing a head and neck unit in a developing country.
AB  - Head and neck cancers pose an especially serious problem in developing countries
      due to late presentation requiring complex surgical intervention. These countries
      are faced with many challenges, ranging from insufficient health care staff to
      problems with peri-operative requirements, diagnostic facilities, chemoradiation
      services and research funding.These challenges can be addressed through the
      training of head and neck surgeons and support personnel, the improvement of
      cancer awareness in local communities, and the establishment of dedicated head
      and neck institutes which focus on the special needs of head and neck cancer
      patients.All these changes can best be achieved through collaborative efforts
      with external partners. The Karl Storz Fellowship in Advanced Head and Neck
      Cancer, enabling training at the University of Cape Town, South Africa, has
      served as a springboard towards establishing head and neck services in developing
      sub-Saharan African countries.

PMID- 22643202
TI  - Recommendations on follow-up strategies for idiopathic vocal fold paralysis:
      evidence-based review.
AB  - INTRODUCTION: Vocal fold paralysis can be an early warning sign of serious extra
      laryngeal pathology. Even if imaging investigations show no pathology, there is
      always concern about the emergence of new pathology in the future. There is
      currently no consensus on the best follow-up protocol for vocal fold paralysis
      patients with no abnormalities on investigation. METHODS: Systematic review,
      using an Ovid and Medline database search of papers written in the English
      language and published in the last 20 years. RESULTS: Eight relevant studies were
      identified. Not all of them were directly comparable. A narrative review of the
      studies is presented and conclusions are drawn. CONCLUSION: Current diagnostic
      modalities are sufficiently reliable and sensitive to diagnose any significant
      existing extra-laryngeal pathology. Thus, once initial investigation (including
      computed tomography) has concluded, no further follow up is necessary.

PMID- 22643203
TI  - Magnetic resonance imaging features of large endolymphatic sac compartments:
      audiological and clinical correlates.
AB  - OBJECTIVES: (1) To study the prevalence and characteristics of large
      endolymphatic sac internal compartments on thin-section T2- and T2*-weighted
      magnetic resonance imaging, and to relate these to other large endolymphatic sac
      magnetic resonance imaging features, and (2) to correlate the compartment imaging
      features, endolymphatic sac size and labyrinthine anomalies with the patients'
      clinical and audiological data. METHOD: Magnetic resonance imaging studies for 38
      patients with large endolymphatic sac anomalies were retrospectively reviewed in
      a tertiary referral centre. Endolymphatic sac compartment presence, morphology
      and imaging signal were assessed. Endolymphatic sac size and labyrinthine
      anomalies were also recorded. Endolymphatic sac compartments and other imaging
      features were correlated with clinical and audiological data. RESULTS:
      Compartments were present in 57 per cent of the imaged endolymphatic sacs, but
      their presence alone did not correlate with other imaging features or clinical
      data. The endolymphatic sac : internal auditory meatus signal ratio was
      associated with a history of sudden or fluctuating hearing loss. Hearing loss
      correlated with opercular and extraosseous endolymphatic sac size measurements. A
      larger midpoint intraosseous endolymphatic sac size was associated with clear
      fluid loss at cochlear implantation. CONCLUSION: The magnetic resonance imaging
      characteristics of large endolymphatic sac compartments have been defined. The
      endolymphatic sac size and distal compartment signal should be recorded, as these
      provide prognostic information and assist the planning of appropriate
      interventions.

PMID- 22643204
TI  - Tracheostomy and laryngectomy survey: do front-line emergency staff appreciate
      the difference?
AB  - BACKGROUND: In an emergency scenario, it is vital to appreciate the difference
      between a laryngectomy and a tracheostomy so that oxygen can be administered in
      an appropriate manner. This survey aimed to ascertain the level of emergency
      healthcare personnel's knowledge with regards to distinguishing between a
      tracheostomy and a laryngectomy patient, and the emergency management of such
      patients. METHODS: Forty-four accident and emergency staff (28 doctors, nine
      nurses and seven paramedics) within one Foundation Trust were invited to complete
      a questionnaire to ascertain (1) their confidence at differentiating between a
      laryngectomy and tracheostomy stoma; (2) knowledge of the appropriate site for
      oxygen delivery if needed; and (3) overall level of training on this subject.
      RESULTS: There were significant gaps in knowledge, particularly with regards to
      fundamental differences between a tracheostomy and a laryngectomy; less than 5
      per cent were able to describe the anatomical difference. Only 41 per cent
      correctly identified the route of oxygen administration in laryngectomy patients.
      CONCLUSION: In this cohort of emergency staff, the fundamental difference between
      a laryngectomy and a tracheostomy was poorly understood. This lack of awareness
      of front-line emergency staff needs to be addressed in order to maximise patient
      safety.

PMID- 22643205
TI  - Tonsillectomy under threat: auditing the indications for performing
      tonsillectomy.
AB  - BACKGROUND: The 2009 McKinsey National Health Service report considered that
      tonsillectomy was relatively ineffective and often unjustified, and that its
      frequently could be greatly reduced. ENTUK argued against this, for severe
      recurrent tonsillitis. This study audited clinical indications for tonsillectomy.
      CRITERIA AND STANDARDS: Current guidelines state that patients with recurrent
      tonsillitis must have disabling sore throat episodes five or more times per year,
      and symptoms for at least a year, to justify tonsillectomy. METHODS: Seventeen
      recurrent tonsillitis patients receiving tonsillectomy were audited
      prospectively. Indications were poorly documented in the referral letter, so
      surgeons agreed to list specified tonsillectomy criteria when scheduling patients
      for tonsillectomy. A pro forma reminder was distributed to all clinics, and the
      next 100 scheduled tonsillectomy patients were audited. RESULTS: In the first
      audit, all 17 tonsillectomies were justified but only two (11.8 per cent) had
      documented indications. In the second audit, 85 per cent of patients had all
      essential criteria, which were documented in the listing letter. CONCLUSION:
      Tonsillectomy risks being removed from the UK essential otolaryngological
      surgical register, risking increased patient morbidity and work absence, despite
      valid supporting evidence of efficacy for recurrent tonsillitis. All UK
      otolaryngology units should strictly adhere to the ENTUK and Scottish
      Intercollegiate Guidelines Network recommendations for tonsillectomy, and should
      document essential criteria in the listing letter, to strengthen the advocacy
      argument for tonsillectomy as essential, valid treatment for recurrent
      tonsillitis.

PMID- 22643206
TI  - Helix advancement meatoplasty.
AB  - We describe a new technique of helix advancement meatoplasty. This technique is
      useful in both mastoid surgery and some cases of otitis externa. The technique is
      designed to avoid the problems of (1) inferior positioning of the meatoplasty at
      the time of surgery, and (2) later inferior migration of the pinna (as can occur
      when the suspensory ligaments of the pinna have been cut or weakened). Such
      outcomes can result in a mastoid cavity which is difficult to clean as the
      approach to it is awkward; in such cases, it is common to have to look up into
      the cavity rather than directly into it. Helix advancement meatoplasty improves
      post-operative visualisation and aeration. It eases cleaning of the cavity by
      creating a more superiorly placed meatoplasty, which is supported by the tragus
      and is therefore less likely to drop.

PMID- 22643207
TI  - Musical hallucination following whiplash injury: case report and literature
      review.
AB  - INTRODUCTION: A musical hallucination is defined as a form of auditory
      hallucination characterised by the perception of music in the absence of external
      acoustic stimuli. It is infrequently cited in the literature, although population
      studies suggest a greater prevalence. The aetiology of this unusual disorder
      remains unclear. CASE REPORT: A 70-year-old man with acquired hearing loss
      suffered a whiplash injury in a low-speed road traffic accident, and subsequently
      presented with bilateral 'tinnitus.' On closer questioning, he described hearing
      orchestral music. There was no evidence of psychosis, delirium or intoxication,
      and the patient was managed expectantly. CONCLUSION: This patient represents the
      first published case of musical hallucination precipitated by whiplash injury. We
      explore the possible pathophysiological underpinnings of musical hallucination
      and highlight the need for a greater awareness of this disorder. A management
      strategy is suggested.

PMID- 22643208
TI  - Coexistence of rhinoscleroma with Rosai-Dorfman disease: is rhinoscleroma a cause
      of this disease?
AB  - INTRODUCTION: Rhinoscleroma and Rosai-Dorfman disease have been reported to
      coexist in the same patient at different sites. Rosai-Dorfman disease may have an
      aetiological relationship with rhinoscleroma, although this has not yet been
      proved. CASE REPORT: A case of a 42-year-old woman with recurrent nasal masses is
      presented, with histopathological proof of both conditions coexisting in the same
      nasal lesion. DISCUSSION: The aetiopathology, clinical features and treatment of
      both diseases are discussed and a literature survey is reported. Histologically,
      the presence of Mikulicz cells with entrapped, rod-like, Gram-negative bacilli
      and Russell bodies suggests rhinoscleroma. Emperipolesis and S-100-positive
      histiocytes confirm the diagnosis of Rosai-Dorfman disease. The presence of both
      in the same slides from affected tissues has never been demonstrated before. In
      the light of this evidence, the author believes that rhinoscleroma must be
      considered in the aetiology of Rosai-Dorfman disease.

PMID- 22643209
TI  - Complete response in a melanoma patient treated with imatinib.
AB  - BACKGROUND: Imatinib therapy has been successful in gastrointestinal stromal
      tumours containing mutation of the KIT gene. However, there are few reported
      cases of successful imatinib therapy in patients with melanoma containing KIT
      gene mutation or c-kit protein expression. METHODS AND RESULTS: A 52-year-old man
      developed metastatic melanoma from a primary melanoma in the left side of the
      nasopharynx. The tumour was positive for c-kit protein, and there was a KIT
      mutation in exon 11. He was treated with imatinib. A follow-up scan one year
      later showed a complete response. Treatment targeting the biological
      characteristics of melanoma proved successful in this patient.

PMID- 22643211
TI  - Aberrant internal carotid artery in the middle ear with dehiscent high jugular
      bulb.
AB  - OBJECTIVE: We report an extremely rare case of an aberrant internal carotid
      artery in the middle ear, together with a dehiscent high jugular bulb, a
      combination never previously reported. METHODS: Case report with a review of the
      literature. RESULTS: A 24-year-old man presented with a five-year history of
      aural fullness, pulsatile tinnitus and mild hearing impairment in his right ear.
      Otoscopy revealed a retro-tympanic mass. Computed tomography of the temporal bone
      revealed protrusion of the right internal carotid artery into the middle-ear
      cavity, with a dehiscent high jugular bulb. Magnetic resonance angiography showed
      a reduced diameter and lateralisation of the right internal carotid artery. A
      diagnosis of an aberrant internal carotid artery with a dehiscent high jugular
      bulb was made, and the patient was managed with conservative treatment.
      CONCLUSION: The otologist should be aware of the possibility of an aberrant
      internal carotid artery when the patient presents with a retro-tympanic mass,
      hearing loss and pulsatile tinnitus. Radiological investigation is required to
      make the differential diagnosis. When an aberrant internal carotid artery
      presents with a dehiscent high jugular bulb, the risk of serious bleeding is
      elevated. We recommend a conservative approach for cases presenting without
      bleeding complications.

PMID- 22643210
TI  - Cervical sparganosis: case reports with focus on radiological findings.
AB  - BACKGROUND: Cervical sparganosis is a rare condition that presents as a lateral
      neck mass. Its radiological findings have not previously been investigated. Thus,
      the important radiological findings of cervical sparganosis are presented herein.
      METHODS: We report two patients with cervical sparganosis who presented with
      cervical masses, and we review the relevant head and neck literature. Computed
      tomography was performed three times over 13 months of follow up for one patient.
      RESULTS: On follow-up radiological examination, a migratory lesion with a tubular
      appearance, seen on serial images, should be considered significant for cervical
      sparganosis. CONCLUSION: Radiologically, a migratory cervical mass in the head
      and neck area with a tubular appearance is suggestive of cervical sparganosis.

PMID- 22643212
TI  - Left-sided neck dissection and chylothorax: a rare complication and its
      management.
AB  - OBJECTIVE: We present a case of bilateral chylothorax, a rare but life
      threatening complication, which developed following a left-sided neck dissection.
      METHOD: Case report and literature review. RESULTS: Chylous leakage fistula is a
      known complication following neck dissection and occurs in 1 to 2 per cent of
      patients. After left-sided neck dissection, chylothorax is uncommon and bilateral
      chylothorax is even rarer. Chylothorax is encountered following certain thoracic
      procedures, especially superior mediastinal dissection for thyroid cancer
      treatment. We discuss in detail the successful management of a complicated case.
      CONCLUSION: We discuss various management options for this condition, and we
      summarise its successful management within our department.

PMID- 22643213
TI  - Improved CD4+ T cell responses to Mycobacterium tuberculosis in PPD-negative
      adults by M72/AS01 as compared to the M72/AS02 and Mtb72F/AS02 tuberculosis
      candidate vaccine formulations: a randomized trial.
AB  - BACKGROUND: The Bacille Calmette-Guerin (BCG) tuberculosis (TB) vaccine provides
      incomplete protection, necessitating development of an effective vaccine against
      TB disease. The Mtb72F/AS02 candidate vaccine was previously shown to be
      clinically well tolerated and immunogenic in Purified Protein Derivative (PPD)
      negative adults. To improve the stability of Mtb72F, a point mutation was
      introduced into a putative serine protease site to give the final M72 construct.
      AS01 is an Adjuvant System that can potentially improve both humoral and cellular
      immune responses compared to the AS02 Adjuvant System or unadjuvanted vaccine.
      This study evaluated the safety and immunogenicity in Mtb-naive adults of
      vaccines containing 40 MUg of the M72 antigen with AS02 or AS01 and compared the
      results with Mtb72F/AS02 vaccine (40 MUg dose), M72 in saline (40 MUg dose) and
      AS01 alone. METHODS: In this Phase I/II observer-blind controlled trial, 110
      participants were randomized (4:4:1:1:1) to receive M72/AS01, M72/AS02,
      Mtb72F/AS02, M72/saline or AS01, following a 0, 1-month schedule. Subjects
      receiving the adjuvanted M72 vaccines were followed up until 3 years post
      vaccination. Evaluation of the immune response and safety/reactogenicity was
      performed. RESULTS: For all vaccines, solicited adverse events (AEs) were
      predominantly mild to moderate and transient. No vaccine-related serious AEs
      occurred and no subject withdrew due to an AE. Immune responses induced by Mtb72F
      and M72 antigens combined with AS02 were similar. M72/AS01 and M72/AS02 induced
      robust polyfunctional M72-specific CD4(+) T cell and antibody responses
      persisting at 3 years, with the highest CD4(+) T cell responses found with
      M72/AS01. CONCLUSION: This first clinical study with M72/AS01 and M72/AS02 showed
      that both vaccines were clinically well tolerated and induced high magnitude and
      persistent cell-mediated and humoral immune responses. The Mtb72F/AS02 and
      M72/AS02 vaccines were comparably immunogenic with significantly higher immune
      responses compared to the M72/saline control. Of the formulations tested,
      M72/AS01 demonstrated significantly higher vaccine specific Th1 CD4(+) T cell
      responses supporting its further clinical evaluation.

PMID- 22643214
TI  - Simultaneous quantification of the viral antigens hemagglutinin and neuraminidase
      in influenza vaccines by LC-MSE.
AB  - Current methods for quality control of inactivated influenza vaccines prior to
      regulatory approval include determining the hemagglutinin (HA) content by single
      radial immunodiffusion (SRID), verifying neuraminidase (NA) enzymatic activity,
      and demonstrating that the levels of the contaminant protein ovalbumin are below
      a set threshold of 1 MUg/dose. The SRID assays require the availability of strain
      specific reference HA antigens and antibodies, the production of which is a
      potential rate-limiting step in vaccine development and release, particularly
      during a pandemic. Immune responses induced by neuraminidase also contribute to
      protection from infection; however, the amounts of NA antigen in influenza
      vaccines are currently not quantified or standardized. Here, we report a method
      for vaccine analysis that yields simultaneous quantification of HA and NA levels
      much more rapidly than conventional HA quantification techniques, while providing
      additional valuable information on the total protein content. Enzymatically
      digested vaccine proteins were analyzed by LC-MS(E), a mass spectrometric
      technology that allows absolute quantification of analytes, including the HA and
      NA antigens, other structural influenza proteins and chicken egg proteins
      associated with the manufacturing process. This method has potential application
      for increasing the accuracy of reference antigen standards and for validating
      label claims for HA content in formulated vaccines. It can also be used to
      monitor NA and chicken egg protein content in order to monitor manufacturing
      consistency. While this is a useful methodology with potential for broad
      application, we also discuss herein some of the inherent limitations of this
      approach and the care and caution that must be taken in its use as a tool for
      absolute protein quantification. The variations in HA, NA and chicken egg protein
      concentrations in the vaccines analyzed in this study are indicative of the
      challenges associated with the current manufacturing and quality control testing
      procedures.

PMID- 22643215
TI  - Nurses' vaccination against pandemic H1N1 influenza and their knowledge and other
      factors.
AB  - This study aimed to estimate the vaccination coverage against the pandemic H1N1
      influenza in a group of nurses and determine the factors associated with their
      vaccination behaviours. An anonymous, self-administered questionnaire was
      distributed to a convenience sample of nurses who were enrolled on continuing
      professional education courses in a university in London. The survey response
      rate was 77.7% (n=522). A total of 172 (35.2%) nurses reported receiving the
      pandemic H1N1 vaccine in the 2009-2010 influenza season and only 22.3% of them
      had the intent to accept the vaccine in the next season. Compared to nurses with
      low knowledge scores, those with high knowledge scores were more likely to
      receive the pandemic H1N1 vaccine (p=0.017), recommend the vaccine to their
      patients (p=0.003), and have the willingness to recommend vaccination to patients
      in the future (p=0.009). There was a higher vaccination rate among nurses with
      higher risk perception scores than with lower scores (p=0.001). A small, positive
      correlation between H1N1 knowledge and risk perception scores was identified
      (p<0.001) indicating that a high knowledge level was associated with high levels
      of risk perception. More male nurses received the H1N1 vaccine than females
      (p<0.001) and there were a significant differences in the uptake among nurses
      from different clinical specialty groups (p<0.001). About half of the vaccinated
      nurses reported the intent to be vaccinated again but only 8.1% of the
      unvaccinated nurses had the intent to receive the vaccine in the next season
      (p<0.001). The pandemic H1N1 2009 influenza vaccination coverage among this nurse
      sample was sub-optional. Lack of knowledge and risk perception were predictors
      associated with the nurses' vaccination behaviours. The identified knowledge
      items should be addressed in future vaccination campaigns. The hindrances
      associated with continuing vaccination decision-making and factors contributing
      to the different vaccination coverage among clinical specialty groups require
      further exploration.

PMID- 22643216
TI  - Factors influencing pandemic influenza vaccination of healthcare workers--a
      systematic review.
AB  - INTRODUCTION: Maintaining the health and availability of Health care workers
      (HCW) is an essential component of pandemic preparedness. A key to protecting HCW
      during the H1N1 pandemic was influenza vaccination. Numerous researchers have
      reported on factors influencing H1N1 vaccination behaviour in various HCW groups.
      This systematic review aims to inform future influenza vaccine interventions and
      pandemic planning processes via the examination of literature in HCW H1N1
      vaccination, in order to identify factors that are (1) unique to pandemic
      influenza vaccination and (2) similar to seasonal influenza vaccination research.
      METHODS: We conducted a comprehensive review of literature (MEDLINE, PubMed,
      EMBASE, PsycINFO, CINHAL, AMED, Cochrane Library, ProQuest, and grey literature
      sources) published between January 2005 and December 2011 to identify studies
      relevant to HCW pH1N1 vaccine uptake/refusal. RESULTS: 20 publications sampling
      HCW from different geographic regions are included in this review. H1N1 vaccine
      coverage was found to be variable (9-92%) across HCW populations, and self
      reported vaccine status was the most frequently utilized predictor of pandemic
      vaccination. HCW were likely to accept the H1N1 vaccine if they perceived, (1)
      the H1N1 vaccine to be safe, (2) H1N1 vaccination to be effective in preventing
      infection to self and others (i.e. loved ones, co-workers and patients), and (3)
      H1N1 was a serious and severe infection. Positive cues to action, such as the
      access of scientific literature, trust in public health communications and
      messaging, and encouragement from loved ones, physicians and co-workers were also
      found to influence HCW H1N1 uptake. Previous seasonal influenza vaccination was
      found to be an important socio-demographic predictor of vaccine uptake. Factors
      unique to HCW pandemic vaccine behaviour are (1) lack of time and vaccine access
      related barriers to vaccination, (2) perceptions of novel and rapid pandemic
      vaccine formulation, and (3) the strong role of mass media on vaccine uptake.
      CONCLUSIONS: Many of the factors that influenced HCW pandemic vaccination
      decisions have previously been reported in seasonal influenza vaccination
      literature, but some factors were unique to pandemic vaccination. Future
      influenza vaccine campaigns should emphasize the benefits of vaccination and
      highlight positive cues to vaccination, while addressing barriers to vaccine
      uptake in order to improve vaccine coverage among HCW populations. Since pandemic
      vaccination factors tend be similar among different HCW groups, successful
      pandemic vaccination strategies may be effective across numerous HCW populations
      in pandemic scenarios.

PMID- 22643217
TI  - Annual influenza vaccination affects the development of heterosubtypic immunity.
AB  - Annual vaccination of healthy children >6 months of age against seasonal
      influenza has been recommended by public health authorities of some countries.
      However, currently used seasonal vaccines provide only limited protection against
      (potentially) pandemic influenza viruses. Furthermore, we recently hypothesized
      that annual vaccination may hamper the development of cross-reactive immunity
      against influenza A viruses of novel subtypes, that would otherwise be induced by
      natural infection. Here we summarize our findings in animal models in which we
      demonstrated that vaccination against influenza A/H3N2 virus reduced the
      induction of heterosubtypic immunity against highly pathogenic avian influenza
      A/H5N1 virus, otherwise induced by a prior infection with influenza A/H3N2 virus.
      The reduction of heterosubtypic immunity correlated with reduced virus-specific
      CD8+ T cell responses. An additional study was performed in humans, in which we
      collected peripheral blood mononuclear cells from annually vaccinated children
      with cystic fibrosis (CF) and age-matched unvaccinated healthy control children
      to study the virus-specific T cell response. An age-related increase of the virus
      specific CD8+ T cell response was observed in unvaccinated children that was
      absent in vaccinated children with CF. These findings highlight the importance of
      the development of vaccines that provide protection against influenza A viruses
      of all subtypes.

PMID- 22643218
TI  - Telomere dysfunction puts the brakes on oncogene-induced cancers.

PMID- 22643219
TI  - Coordinated signal integration at the M-type potassium channel upon muscarinic
      stimulation.
AB  - Several neurotransmitters, including acetylcholine, regulate neuronal tone by
      suppressing a non-inactivating low-threshold voltage-gated potassium current
      generated by the M-channel. Agonist dependent control of the M-channel is
      mediated by calmodulin, activation of anchored protein kinase C (PKC), and
      depletion of the phospholipid messenger phosphatidylinositol 4,5-bisphosphate
      (PIP2). In this report, we show how this trio of second messenger responsive
      events acts synergistically and in a stepwise manner to suppress activity of the
      M-current. PKC phosphorylation of the KCNQ2 channel subunit induces dissociation
      of calmodulin from the M-channel complex. The calmodulin-deficient channel has a
      reduced affinity towards PIP2. This pathway enhances the effect of concomitant
      reduction of PIP2, which leads to disruption of the M-channel function. These
      findings clarify how a common lipid cofactor, such as PIP2, can selectively
      regulate ion channels.

PMID- 22643221
TI  - Up for grabs; trashing peroxisomes.

PMID- 22643220
TI  - Pex3-anchored Atg36 tags peroxisomes for degradation in Saccharomyces cerevisiae.
AB  - Peroxisomes undergo rapid, selective autophagic degradation (pexophagy) when the
      metabolic pathways they contain are no longer required for cellular metabolism.
      Pex3 is central to the formation of peroxisomes and their segregation because it
      recruits factors specific for these functions. Here, we describe a novel
      Saccharomyces cerevisiae protein that interacts with Pex3 at the peroxisomal
      membrane. We name this protein Atg36 as its absence blocks pexophagy, and its
      overexpression induces pexophagy. We have isolated pex3 alleles blocked
      specifically in pexophagy that cannot recruit Atg36 to peroxisomes. Atg36 is
      recruited to mitochondria if Pex3 is redirected there, where it restores
      mitophagy in cells lacking the mitophagy receptor Atg32. Furthermore, Atg36 binds
      Atg8 and the adaptor Atg11 that links receptors for selective types of autophagy
      to the core autophagy machinery. Atg36 delivers peroxisomes to the
      preautophagosomal structure before being internalised into the vacuole with
      peroxisomes. We conclude that Pex3 recruits the pexophagy receptor Atg36. This
      reinforces the pivotal role played by Pex3 in coordinating the size of the
      peroxisome pool, and establishes its role in pexophagy in S. cerevisiae.

PMID- 22643223
TI  - Novel formulations of dipyridamole with microenvironmental pH-modifiers for
      improved dissolution and bioavailability under hypochlorhydria.
AB  - This study was undertaken to develop new dipyridamole (DP) formulations with
      acidic microenvironmental pH-modifiers for improving dissolution and absorption
      under hypochlorhydric conditions. Dipyridamole granules (DPG) with ten acidic pH
      modifiers were prepared with conventional wet granulation, and their
      manufacturability, stability and dissolution behavior were characterized.
      Pharmacokinetic profiling of the optimized DPG with acid was carried out in
      omeprazole-treated rats as a hypochlorhydric model. On the basis of the
      manufacturability, stability and dissolution behavior of new DPG formulations, p
      toluenesulfonic acid (TS) was found to be a suitable acidic pH-modifier for DPG
      formulation. Although DPG showed pH-dependent dissolution behavior, DPG with TS
      exhibited a high rate and extent of dissolution in both acidic and neutral media.
      After oral administration of DPG (10mg DP/kg) in omeprazole-treated
      hypochlorhydric rats, there was ca. 40% reduction of the area under the curve of
      plasma concentration vs. time from zero to 3h (AUC(0-3)) for DPG compared with
      that in normal rats. However, AUC(0-3) for DPG/TS under hypochlorhydria was
      almost identical to that of DPG in normal rats. From these findings, the addition
      of TS as a microenvironmental pH-modifier in DP formulation might be beneficial
      in expanding the therapeutic potential of DP in hypochlorhydric patients.

PMID- 22643222
TI  - Inactivation of Rb in stromal fibroblasts promotes epithelial cell invasion.
AB  - Stromal-derived growth factors are required for normal epithelial growth but are
      also implicated in tumour progression. We have observed inactivation of the
      retinoblastoma protein (Rb), through phosphorylation, in cancer-associated
      fibroblasts in oro-pharyngeal cancer specimens. Rb is well known for its cell
      autonomous effects on cancer initiation and progression; however, cell non
      autonomous functions of Rb are not well described. We have identified a cell non
      autonomous role of Rb, using three-dimensional cultures, where depletion of Rb in
      stromal fibroblasts enhances invasive potential of transformed epithelia. In
      part, this is mediated by upregulation of keratinocyte growth factor (KGF), which
      is produced by the depleted fibroblasts. KGF drives invasion of epithelial cells
      through induction of MMP1 expression in an AKT- and Ets2-dependent manner. Our
      data identify that stromal fibroblasts can alter the invasive behaviour of the
      epithelium, and we show that altered expression of KGF can mediate these
      functions.

PMID- 22643224
TI  - Enhanced solubility and oral bioavailability of itraconazole by combining
      membrane emulsification and spray drying technique.
AB  - The objective of the present study was to enhance solubility and bioavailability
      of itraconazole by a combined use of membrane emulsification and spray drying
      solidification technique. A shirasu-porous-glass (SPG) membrane with a mean pore
      size of 2.5 MUm was used to produce monodispersed microemulsions of itraconazole
      consisting of methylene chloride as the dispersed phase, a mixture of Transcutol
      HP and Span 20 as a stabilizer, and dextran as solid carrier dissolved in water
      as the continuous phase. The dispersed phase permeated through the SPG membrane
      into the continuous phase at an agitator speed of 150 rpm, a feed pressure of 15
      kPa and a continuous phase temperature of 25 degrees C and the resultant emulsion
      was solidified using spray-drying technique. Solid state characterizations of the
      solid emulsion showed that the crystal state of itraconazole in solid emulsion
      was converted from crystalline to amorphous form. The solid emulsion of
      itraconazole displayed a significant increase in the dissolution rate than that
      of pure itraconazole. Furthermore, the solid emulsion after oral administration
      gave about eight-fold higher AUC and about ten-fold higher C(max) in rats than
      pure itraconazole powder (p<0.05), indicating this formulation greatly improved
      the oral bioavailability of drug in rats. Thus, these results demonstrated that
      the SPG membrane emulsification system combined with spray-drying technique could
      be used as a promising technique to develop solid formulation of itraconazole
      with enhanced solubility and bioavailability.

PMID- 22643225
TI  - Treatments of paclitaxel with poly(vinyl pyrrolidone) to improve drug release
      from poly(E-caprolactone) matrix for film-based stent.
AB  - Drug-loaded biodegradable films as a principal part of film-based stent were
      investigated for controlled drug delivery systems. In this study, solid
      dispersion technique, a pretreatment method of paclitaxel (PTX), was applied to
      prepare the PTX-loaded poly(E-caprolactone) (PCL) films. Drug dissolution rates
      and characteristics of the poly(vinyl pyrrolidone) (PVP)/PTX solid dispersions
      (SDs) and physical mixtures (PMs) were investigated to show that the PVP/PTX SDs
      were successfully prepared before being incorporated in biodegradable films.
      Afterwards, the effect of the application of SDs on improving drug release
      behavior, weightlessness, crystalline states, and surface and internal
      morphologies of the films were studied. It was found that, the films with SDs
      showed a higher drug release rate than the films with PMs or pure PTX. In
      addition, the content of PVP in the SDs also had impact on drug release behavior:
      the more PVP in SDs, the faster the drug was released. According to the drug
      release test and weightlessness study, the possible drug release mechanism was
      put forward for the films with SDs. The application of solid dispersion technique
      showed a remarkable effect on improving drug release behavior for film-based
      biodegradable stent drug delivery systems.

PMID- 22643226
TI  - Alginate based bilayer hydrocolloid films as potential slow-release modern wound
      dressing.
AB  - The aims of this research were to develop a novel bilayer hydrocolloid film based
      on alginate and to investigate its potential as slow-release wound healing
      vehicle. The bilayer is composed of an upper layer impregnated with model drug
      (ibuprofen) and a drug-free lower layer, which acted as a rate-controlling
      membrane. The thickness uniformity, solvent loss, moisture vapour transmission
      rate (MVTR), hydration rate, morphology, rheology, mechanical properties, in
      vitro drug release and in vivo wound healing profiles were investigated. A smooth
      bilayer film with two homogenous distinct layers was produced. The
      characterisation results showed that bilayer has superior mechanical and
      rheological properties than the single layer films. The bilayers also showed low
      MVTR, slower hydration rate and lower drug flux in vitro compared to single layer
      inferring that bilayer may be useful for treating low suppurating wounds and
      suitable for slow release application on wound surfaces. The bilayers also
      provided a significant higher healing rate in vivo, with well-formed epidermis
      with faster granulation tissue formation when compared to the controls. In
      conclusions, a novel alginate-based bilayer hydrocolloid film was developed and
      results suggested that they can be exploited as slow-release wound dressings.

PMID- 22643227
TI  - In vitro and in vivo evaluation of N,N,N-trimethylphytosphingosine-iodide (TMP)
      in liposomes for the treatment of angiogenesis and metastasis.
AB  - Phytosphingosine and methyl derivatives are important mediators on cellular
      processes, and are associated with cell growth and death. The antitumor activity
      of N,N,N-trimethylphytosphingosine-iodide (TMP) as a novel potent inhibitor of
      angiogenesis and metastasis was evaluated in B16F10 murine melanoma cells. The
      results indicated that TMP itself effectively inhibited in vitro cell migration,
      tube formation, and the expression of angiogenic factors as well as in vivo lung
      metastasis. However, TMP slightly suppressed in vivo experimental tumor
      metastasis in its free form and induced side effects including hemolysis and
      local side effects. Therefore, in an attempt to reduce the toxicity and the
      undesirable side effects of TMP, a liposomal formulation was prepared and tested
      for its effectiveness. TMP liposomes retained the effectiveness of TMP in vitro
      while side effects were reduced, and both in vivo experimental and spontaneous
      tumor metastasis were significantly suppressed. These results support the
      conclusion that TMP effectively inhibits in vitro angiogenesis as well as in vivo
      metastasis, and a liposomal formulation is more efficient delivery system for TMP
      treatment than solution.

PMID- 22643228
TI  - Comparative study on preparative methods of DC-Chol/DOPE liposomes and
      formulation optimization by determining encapsulation efficiency.
AB  - Three most commonly used preparative methods, dry-film, reverse phase evaporation
      and ethanol injection were employed to prepare cationic liposomes composed of DC
      Chol and DOPE, respectively. The resulting samples were contrasted through
      morphology observation, particle size and zeta potential analysis. Sephadex
      filtration method with high selectivity was developed to determine the
      encapsulation efficiency of plasmid DNA-loaded cationic vectors, on this basis,
      cationic liposomes formulation was further optimized by applying Box Behnken
      design with encapsulation efficiency as evaluation index. The results showed that
      liposomes prepared by dry-film method were of best quality and stability,
      moreover, the optimum formulation of cationic liposomes and optimal value of each
      influencing factors were quantitatively obtained, measured value was highly
      consistent with predicted results. These findings preliminarily clarified the
      effect of preparative methods on performance of cationic liposome, as well as
      formulation factors on encapsulation efficiency, and will provide important
      methodological reference for further study of liposomes carriers for gene
      delivery.

PMID- 22643229
TI  - Symptom clusters during the late reproductive stage through the early
      postmenopause:  observations from the Seattle Midlife Women's Health Study.
AB  - OBJECTIVE: The aim of this study was to identify symptom clusters that
      characterize women's experiences through the late reproductive stage, the
      menopausal transition, and early postmenopause and to explore the influence of
      the menopausal transition stages and early postmenopause, compared with that of
      the late reproductive stage, on the clusters of symptoms women experience.
      METHODS: Participants from the Seattle Midlife Women's Health Study whose symptom
      calendars were staged for the menopausal transition provided data for a total of
      6,857 occasions. Multilevel latent class analysis was used to identify classes
      using scores for hot flashes and symptom factors (sleep, cognitive, mood, pain,
      tension). RESULTS: Class 1 included observations of low severity levels for all
      symptoms, whereas class 2 included low-severity hot flashes and moderate-severity
      levels for all other symptom factors. Class 3 included high severity hot flashes
      with lower severity levels of all other symptom factors. During the early and
      late menopausal transition stages and early postmenopause, the likelihood of
      being in class 3 was significantly greater than being in class 1 relative to the
      late reproductive stage. There were no significant effects of the menopausal
      transition stages on the likelihood of being in class 2. CONCLUSIONS: This effort
      is the first to examine the latent classes or clusters of symptoms during the
      prolonged period from late reproductive stage to early postmenopause. As such,
      the data contribute to the understanding of symptom experiences beyond our early
      efforts to characterize the late menopausal transition stage.

PMID- 22643230
TI  - Dopaminergic amacrine cells express opioid receptors in the mouse retina.
AB  - The presence of opioid receptors has been confirmed by a variety of techniques in
      vertebrate retinas including those of mammals; however, in most reports, the
      location of these receptors has been limited to retinal regions rather than
      specific cell types. Concurrently, our knowledge of the physiological functions
      of opioid signaling in the retina is based on only a handful of studies. To date,
      the best-documented opioid effect is the modulation of retinal dopamine release,
      which has been shown in a variety of vertebrate species. Nonetheless, it is not
      known if opioids can affect dopaminergic amacrine cells (DACs) directly, via
      opioid receptors expressed by DACs. This study, using immunohistochemical
      methods, sought to determine whether (1) MU- and delta-opioid receptors (MORs and
      DORs, respectively) are present in the mouse retina, and if present, (2) are they
      expressed by DACs. We found that MOR and DOR immunolabeling were associated with
      multiple cell types in the inner retina, suggesting that opioids might influence
      visual information processing at multiple sites within the mammalian retinal
      circuitry. Specifically, colabeling studies with the DAC molecular marker anti
      tyrosine hydroxylase antibody showed that both MOR and DOR immunolabeling
      localize to DACs. These findings predict that opioids can affect DACs in the
      mouse retina directly, via MOR and DOR signaling, and might modulate dopamine
      release as reported in other mammalian and nonmammalian retinas.

PMID- 22643231
TI  - Structures and absolute stereochemistry of dinapinones A1 and A2, inhibitors of
      triacylglycerol synthesis, produced by penicillium pinophilum FKI-3864.
AB  - During our screening program for microbial inhibitors of triacylglycerol
      synthesis in mammalian cells, four structurally related new compounds,
      dinapinones A1 (1) and A2 (2) and monapinones A (3) and B (4), were isolated from
      the culture broth of Penicillium pinophilum FKI-3864. Compounds 3 and 4 were
      produced by the fungus only when fermented in seawater-supplemented medium. The
      structures of 1 to 4 were elucidated by spectroscopic studies including various
      NMR experiments. Compounds 1 and 2 were atropisomers consisting of two monomers
      with the same planar structure of dihydronaphthopyranone as 3. The absolute
      stereochemistry of 3 was elucidated by NOE experiment and circular dichroism
      spectra. Furthermore, the stereochemistry of 1 and 2 was elucidated by in vitro
      conversion from the structure-defined 3 to its dimers 1 and 2.

PMID- 22643232
TI  - Garcinia buchananii bark extract is an effective anti-diarrheal remedy for
      lactose-induced diarrhea.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The extract from the stem bark of Garcinia
      buchananii trees is used as an anti-diarrhea remedy in sub-Saharan Africa. We
      tested the hypothesis that G. buchananii bark extract and its anti-motility
      fractions are effective treatments against lactose-induced diarrhea. MATERIALS
      AND METHODS: A high-lactose (35%) diet was used to induce diarrhea in Wistar
      rats, which were then treated with either G. buchananii bark extract (0.1, 0.5,
      1.0 and 5.0 g bark powder), and its anti-motility fractions isolated using
      preparative thin layer chromatography; termed PTLC1 (15 mg) and PTLC5 (3.8 mg) or
      loperamide (8.4 mg). Drug preparations were dissolved in 1L except PTCL1 and
      PTLC5 that were dissolved in 100mL tap water. Numerous parameters were measured
      in each condition including consistency, fluid and mucus content of feces, body
      weight, water and food consumption, urine production and bloating. RESULTS:
      Diarrheic rats produced watery or loose, mucuoid, sticky, feces. Fluids
      constituted 86% of stool mass compared with only 42% for control rats fed
      standard chow. Compared with controls, diarrheic rats produced more urine, lost
      weight and had bloated ceca and colons. All doses of the extract, its anti
      motility fractions and loperamide individually stopped diarrhea within 6-24 h of
      administration, whilst significantly reducing mucus and fecal fluid content,
      urine production and intestinal bloating. Rats treated with 0.1g extract, PTLC1
      and PTLC5 gained weight, whilst PTLC5 also increased water intake. CONCLUSIONS:
      Garcinia buchananii extract and its anti-motility fractions are effective
      remedies against lactose-induced diarrhea. The extract contains compounds that
      reverse weight loss, promote food and water intake, supporting the notion that
      characterization of the compounds could lead to new therapies against diarrheal
      diseases.

PMID- 22643233
TI  - Region-specific differences in brain melanocortin receptors in rats of the lean
      phenotype.
AB  - The brain melanocortin (MC) system is one of numerous overlapping systems
      regulating energy balance; it consists of peptides including alpha-melanocyte
      stimulating hormone that act through melanocortin receptors (MCRs). Mutations and
      polymorphisms in MC3R and MC4R have been identified as one of the most common
      genetic contributors to obesity in human studies. Brain MC3R and MC4R are known
      to modulate energy expenditure (EE) and food intake, but much less is known
      regarding brain MC5R. To test the hypothesis that brain MC modulates physical
      activity (PA) and EE, we compared brain MCR profiles in rats that consistently
      show high versus low levels of 'spontaneous' daily PA. Compared with low-activity
      rats, high-activity rats show enhanced mRNA expression of MCRs in the brain,
      specifically of MC3R in the paraventricular nucleus (PVN), and MC4R and MC5R in
      the perifornical lateral hypothalamus. Next, we microinjected the MCR agonist
      melanotan II into the PVN region and measured PA and EE. Intra-PVN melanotan II
      induced a dose-dependent increase in PA and this effect was greater in high
      activity rats compared with low-activity rats. These results indicate region
      specific brain MCR expression in the heightened PA seen in association with high
      endurance capacity and identify promising targets in the brain MC system that may
      contribute to interindividual variability in energy balance.

PMID- 22643234
TI  - Age-related multisensory integration elicited by peripherally presented
      audiovisual stimuli.
AB  - Although age-related multisensory integration has been investigated previously,
      the effects of aging on multisensory integration elicited by peripherally
      presented audiovisual (AV) stimuli remain unclear. In this study, visual,
      auditory, and AV stimuli were randomly presented to the left or the right of the
      central fixation point; during this time, participants (young and old adults)
      were asked to respond promptly to target stimuli. Using a race model to analyze
      the response times, our results showed that the AV behavioral facilitation of
      young participants was significant (P<0.05), with response times ranging from 240
      to 450 ms and peaking at 360 ms (14%). However, the AV behavioral facilitation of
      elderly participants was delayed and showed an extensive range, with response
      times ranging from 260 to 540 ms and with a lower peak (12.6%) and delay time
      (390 ms). We found that the time window of AV behavioral facilitation in elderly
      participants was longer but more delayed than that in the young participants when
      the AV stimuli were presented peripherally. This finding also further confirmed
      that peripheral resolution decreased with age.

PMID- 22643235
TI  - Perlecan domain V is upregulated in human brain arteriovenous malformation and
      could mediate the vascular endothelial growth factor effect in lesional tissue.
AB  - Brain arteriovenous malformation (BAVM), a rare but important cause of
      intracranial hemorrhage, has increased angiogenesis and inflammation as key
      components of the nidus of abnormal vessels and stroma that form the resected
      surgical specimen. Accordingly, both vascular endothelial growth factor (VEGF)
      and transforming growth factor-beta have been implicated in the pathology of BAVM
      for their proangiogenic and vascular-regulating roles. The C-terminal fragment of
      the extracellular matrix component perlecan (domain V, DV) has been shown to be
      increased and through the alpha5beta1 integrin, to increase VEGF levels in and
      around areas of cerebral ischemic injury, another proangiogenic condition. We
      aimed to determine whether the concentrations of DV, DV's proangiogenic receptor
      alpha5beta1 integrin, or DV's antiangiogenic receptor alpha2beta1 integrin are
      elevated in human BAVM tissue. DV levels were increased in BAVM compared with
      control brain tissue from epileptic resection, as was alpha5beta1 integrin. In
      addition, alpha5beta1 integrin was preferentially increased and localized to
      endothelial cells compared with alpha2beta1 integrin. VEGF and transforming
      growth factor-beta levels were also increased in BAVM compared with control
      tissue. Furthermore, increases in all components were strongly correlated.
      Excessive generation of proangiogenic DV in BAVM suggests that DV may participate
      in its pathology and may represent a future therapeutic target.

PMID- 22643236
TI  - Functional plasticity of surround inhibition in the motor cortex during single
      finger contraction training.
AB  - We investigated the functional changes in short intracortical inhibitory (SICI)
      circuits to determine whether surround inhibition is altered during a simple
      finger movement training. Using an electromyographic (EMG) feedback system linked
      to a computer monitor, participants practiced sustained index finger abduction by
      40% maximum voluntary contraction of the first dorsal interosseous (FDI) while
      decreasing overflow EMG activity of the abductor digiti minimi (ADM) to less than
      5% maximum voluntary contraction. Single transcranial magnetic stimuli (TMS) and
      paired-pulse TMS were applied to the left primary motor cortex to elicit motor
      evoked potentials (MEPs) in the right FDI and ADM before/after training. In
      addition to recording MEPs from both muscles during voluntary FDI contraction,
      MEPs were recorded during motor imagery. MEPs from the FDI were not altered by
      training, indicating no functional changes in SICI circuits associated with the
      FDI field. In contrast, SICI circuits associated with ADM were significantly
      strengthened by training, as indicated by reduced baseline EMG activity during
      both actual FDI contraction and motor imagery and by reduced MEPs in response to
      post-training TMS. We propose that SICI circuits show functional plasticity
      during motor training and that surround circuit inhibition of nontarget muscle
      groups increases in proportion to the acquisition of motor skills.

PMID- 22643237
TI  - Getting to know you:  the acquisition of new face representations in autism
      spectrum conditions.
AB  - Social difficulties form a part of the canonical description of autism spectrum
      conditions (ASC), and the development of familiarity with new faces is a key
      ability required to navigate the social world. Here, we investigated the
      acquisition of new face representations in ASC by analysing the N170 and N250
      event-related potential components induced by a previously unfamiliar face that
      was embedded in a series of other unfamiliar faces. We found that participants
      with ASC developed a smaller N250 component to the target face, indicating that
      the development of new face representations is impaired. We also found that the
      participants with ASC showed a smaller N170 component to both the target and the
      nontarget faces. This highlights the role of the early stages of face detection,
      structural encoding and attention in the formation of face memories in the
      typical population and implicates the dysfunction of these stages in the
      manifestation of the social difficulties observed in ASC.

PMID- 22643238
TI  - Lesion of area postrema attenuated hyperphagic responses to glucoprivation, but
      not transcriptional activation of the neuropeptide Y gene in rats.
AB  - The area postrema (AP) is a circumventricular organ that lacks a blood-brain
      barrier. Previous studies have shown that the lesion of AP (APX) attenuated
      hyperphagic responses to glucoprivation. As the orexigenic neuropeptide Y (NPY)
      neurons have been implicated in the regulation of food intake, we examined
      whether the activation of NPY neurons by glucoprivation is mediated through the
      AP as well. In agreement with previous studies, hyperphagic responses to an
      injection of 2-deoxy-D-glucose that blocks glucose utilization were significantly
      attenuated in the APX group compared with the sham-operated (Sham) group.
      However, the expression levels of NPY heteronuclear RNA, a sensitive indicator
      for the gene transcription, were significantly increased in the arcuate nucleus
      by a 2-deoxy-D-glucose injection in both the APX and the Sham groups, and there
      were no significant differences in the values between groups. These data suggest
      that the hyperphagic response to glucoprivation, but not the activation of NPY
      gene transcription in the arcuate nucleus, was mediated through the AP in the
      hindbrain.

PMID- 22643239
TI  - Expressing urine from a gel disposable diaper for biomonitoring using phthalates
      as an example.
AB  - The urinary metabolites of phthalates are well-accepted exposure biomarkers for
      adults and children older than 6 years but are not commonly used for infants
      owing to non-convenient sampling. In the light of this situation, a novel
      sampling method based on monitoring the urine expressed from the gel diaper was
      developed. The urine was expressed from the gel absorbent after mixing the
      absorbent with CaCl(2) and then collected by a laboratory-made device; the
      urinary phthalate metabolites were extracted and cleaned using a solid-phase
      extraction (SPE) column and analyzed with high-performance liquid chromatography
      electrospray ionization-tandem mass spectrometry / mass spectrometry. To evaluate
      the method's feasibility, the following factors were investigated: the proportion
      of CaCl(2) to gel absorbent, the urination volume variation and the target
      compounds' deposition bias in the diaper, the matrix blank of the different
      diaper brands, the storage stabilities and the recoveries of creatinine and
      phthalate metabolites in the expressed urine. Mono-methyl phthalate, mono-ethyl
      phthalate, mono-butyl phthalate, mono-benzyl phthalate, mono-2-ethylhexyl
      phthalate and mono-2-ethyl-5-oxohexyl phthalate were involved. 70-80% of the
      urine can be expressed from the diaper, and the expressed spiking recoveries and
      the limit of detection of mono-phthalates ranged from 88.5-115% and 0.21-0.50
      ng/ml. The method was applied to measure phthalate metabolites in 65 gel diaper
      samples from 15 infants, and the pilot data suggests the infants are commonly
      exposed to phthalates. In summary, the method for monitoring of infant exposure
      to phthalates is sound and validated, and the potential health effects from the
      vulnerable infants' exposure to phthalates should be concerned.

PMID- 22643240
TI  - Optimization of the HepaRG cell model for drug metabolism and toxicity studies.
AB  - The HepaRG cell line is the first human cell line able to differentiate in vitro
      into mature hepatocyte-like cells. Our main objective within the framework of the
      EEC-LIINTOP project was to optimize the use of this cell line for drug metabolism
      and toxicity studies, especially after repeat treatments. The main results showed
      that differentiated HepaRG cells: (i) retained their drug metabolism capacity
      (major CYPs, phase 2 enzymes, transporters and nuclear receptors) and
      responsiveness to prototypical inducers at relatively stable levels for several
      weeks at confluence. The levels of several functions, including some CYPs such as
      CYP3A4, were dependent on the addition of dimethyl sulfoxide in the culture
      medium; (ii) sustained the different types of chemical-induced hepatotoxicity,
      including steatosis, phospholipidosis and cholestasis, after acute and/or repeat
      treatment with reference drugs. In particular, drug-induced vesicular steatosis
      was demonstrated in vitro for the first time. In conclusion, our results from the
      LIINTOP project, together with other studies reported concomitantly or more
      recently in the literature, support the conclusion that the metabolically
      competent human HepaRG cells represent a surrogate to primary human hepatocytes
      for investigating drug metabolism parameters and both acute and chronic effects
      of xenobiotics in human liver.

PMID- 22643241
TI  - Phorbol ester-modulation of estrogenic genomic effects triggered by the
      environmental contaminant benzanthracene.
AB  - Aryl hydrocarbon receptor-dependent genomic effects of environmental polycyclic
      aromatic hydrocarbons (PAHs) have been shown to be modulated by non-genomic
      protein kinase C (PKC)-related pathways. The present study was designed to
      determine whether PKC activation may also impair estrogenic genomic response
      triggered by PAHs. Treatment by the PKC activator phorbol 12-myristate 13-acetate
      (PMA) was found to markedly and differentially impair the up-regulation of
      estrogenic markers triggered by the estrogenic PAH benzanthracene (BZA) in
      cultured human mammary cells; BZA-mediated mRNA up-regulation of pS2 and
      amphiregulin was thus increased, whereas that of progesterone receptor and CXCL12
      was repressed. BZA/PMA cotreatment however failed to alter BZA-mediated increase
      of activity of a luciferase gene reporter construct driven by an estrogen
      response element, thus discarding any global effect of PMA toward BZA-triggered
      estrogen receptor activation. Various chemicals inhibiting PKCs or extracellular
      signal-regulated kinase (ERK) as well as the knock-down of PKCdelta expression
      counteracted the PMA-mediated increase of pS2 mRNA up-regulation triggered by
      BZA, demonstrating that it was dependent on PKCs, including PKCdelta isoform, and
      ERKs. This non-genomic modulation of estrogenic effects of PAHs by PKC activation
      may have to be considered when considering the deleterious effects of these
      environmental contaminants towards the endocrine system.

PMID- 22643243
TI  - Surgical management of a symptomatic foregut duplication cyst.

PMID- 22643242
TI  - Protein v. carbohydrate intake differentially affects liking- and wanting-related
      brain signalling.
AB  - Extreme macronutrient intakes possibly lead to different brain signalling. The
      aim of the present study was to determine the effects of ingesting high-protein
      v. high-carbohydrate food on liking and wanting task-related brain signalling
      (TRS) and subsequent macronutrient intake. A total of thirty female subjects
      (21.6 (SD 2.2) years, BMI 25.0 (SD 3.7) kg/m2) completed four functional MRI
      scans: two fasted and two satiated on two different days. During the scans,
      subjects rated all food items for liking and wanting, thereby choosing the
      subsequent meal. The results show that high-protein (PROT) v. high-carbohydrate
      (CARB) conditions were generated using protein or carbohydrate drinks at the
      first meal. Energy intake and hunger were recorded. PROT (protein: 53.7 (SD 2.1)
      percentage of energy (En%); carbohydrate: 6.4 (SD 1.3) En%) and CARB conditions
      (protein: 11.8 (SD 0.6) En%; carbohydrate: 70.0 (SD 2.4) En%) were achieved
      during the first meal, while the second meals were not different between the
      conditions. Hunger, energy intake, and behavioural liking and wanting ratings
      were decreased after the first meal (P< 0.001). Comparing the first with the
      second meal, the macronutrient content changed: carbohydrate -26.9 En% in the
      CARB condition, protein -37.8 En% in the PROT condition. After the first meal in
      the CARB condition, wanting TRS was increased in the hypothalamus. After the
      first meal in the PROT condition, liking TRS was decreased in the putamen (P<
      0.05). The change in energy intake from the first to the second meal was
      inversely related to the change in liking TRS in the striatum and hypothalamus in
      the CARB condition and positively related in the PROT condition (P< 0.05). In
      conclusion, wanting and liking TRS were affected differentially with a change in
      carbohydrate or protein intake, underscoring subsequent energy intake and shift
      in macronutrient composition.

PMID- 22643244
TI  - Laparoscopic longitudinal jejunectomy for intussusception after gastric bypass.

PMID- 22643245
TI  - Transverse mesocolic hernia after retrocolic retrogastric laparoscopic gastric
      bypass.

PMID- 22643246
TI  - Closure of gastrocutaneous fistula using autologous blood product sealant.

PMID- 22643247
TI  - A large solitary desmoplastic small round cell tumor.

PMID- 22643248
TI  - Isolated traumatic shoulder disarticulation after a motor vehicle collision.

PMID- 22643249
TI  - A case of peritoneal squamous metaplasia arising within obstructed small bowel: a
      rare pathological finding during a common surgical event.

PMID- 22643250
TI  - Solitary fibrous tumor in solid organs: still a challenging diagnosis.

PMID- 22643251
TI  - Angiolipoma of the neck.

PMID- 22643252
TI  - Traumatic hemipelvectomy: a survivor of a catastrophic injury.

PMID- 22643253
TI  - Mucinous adenocarcinoma of the anal canal.

PMID- 22643254
TI  - Surgical management of cystic adventitial disease of the popliteal artery.

PMID- 22643255
TI  - Staying the course.
AB  - Much has been written about public hospitals relative to their mission to care
      for the underserved, their role in medical education, and the continuous
      financial challenges that they encounter. But, despite doubts about their
      viability, public hospitals have not only withstood the test  of time, but have
      thrived and have evolved into a new entity, i.e., the safety net hospital. Like
      with any long-standing institution, the development of public hospitals holds
      valuable lessons that provide insight into how they will continue to evolve and
      potentially strengthen, even in the  face of adversity. Their rich heritage
      includes many medical "firsts" in the United States such as the first municipal
      ambulance service, first blood bank, first trauma center(s), first cardiac
      catherization, and first civilian burn center. If safety net hospitals care for
      their  communities and continue in their educational mission, they will thrive in
      the tradition of service.

PMID- 22643256
TI  - Cost analysis of laparoscopic versus open colectomy in patients with colon
      cancer: results from a large nationwide population database.
AB  - Laparoscopic colectomy (LC) is a safe and reliable option for patients with colon
      cancer. This study examined factors associated with LC use and cost differences
      between LC and open colectomy (OC). Using the Cost & Utilization Project National
      Inpatient Sample database (2008), patients  with colon cancer undergoing elective
      LC or OC were selected. Chi square and Mann-Whitney tests were used to assess
      differences between LC and OC. Logistic and multiple regression analysis was used
      to determine variables associated with LC and predictors of cost. All analysis
      was weighted.  A total of 63,950 patients were identified (LC 8.1%, OC 91.9%).
      The majority was female (52.7%), white (61.4%), using Medicare (61.1%), and had
      surgery performed at a large (64.2%), nonteaching (56.9%), urban (87.3%) hospital
      in the South (37.7%). Mean age was 70 years. On unadjusted analysis,  LC was
      associated with a lower mortality rate (1.7 vs 2.4%), fewer complications (18.9
      vs 27.1%), shorter length of stay (5 vs 7 days), and lower total charges ($41,971
      vs $43,459, all P < 0.001). LC is a less expensive but less popular surgical 
      option for colon cancer. Stage, race, Charlson score, teaching status, location,
      and hospital size influence the use of a laparoscopic approach. LC is associated
      with fewer complications and decreased mortality which contribute to its lower
      cost as compared with OC.

PMID- 22643257
TI  - Resident perceptions of the impact of paging on intraoperative education.
AB  - Our purpose was to evaluate the impact of paging on perceptions of intraoperative
      learning. Intraoperative logs of pager interruptions were kept by surgical
      residents at a university hospital over a 30-day period. The postgraduate year,
      number of pages, category of caller, reason for  call, and level of urgency were
      recorded during each operation. At the conclusion of each operation, residents
      also completed a two-item survey with responses on a 5-point scale (1 = strongly
      disagree to 5 = strongly agree), querying if interruptions negatively impacted
      the intraoperative  experience and if a message taken by a third party was
      effective in limiting interruptions. Logs were completed for 124 of 204
      operations. Fifty-five per cent of operations were interrupted at least once with
      49 per cent interrupted two to five times and 6 per cent were interrupted six or 
      more times. Junior residents had 69 per cent of their operations interrupted
      compared with 39 per cent of senior residents (P = 0.001). Ninety-two per cent of
      pages were nonurgent. Residents did not perceive pager interruptions negatively
      impacted their educational experience (mean  2.3) but were neutral with respect
      if messages taken by a third party decreased interruptions (mean 3.8). Although
      our hypothesis was that pager interruptions were frequent and disrupt resident
      education, our data demonstrate the opposite.

PMID- 22643258
TI  - Surgical management of malignant bowel obstruction: at what price palliation?
AB  - Several options exist to palliate malignant obstruction (MBO), none of which have
      established consensus among surgeons. The purpose of this study was to establish
      outcomes of diverting stoma (DS), internal bypass (IB), and palliative resection
      (PR) for a tertiary academic referral surgical  oncology service. All patients
      presenting to a surgical oncology service with malignant bowel obstruction over a
      3-year period were identified. Records were reviewed to determine success of
      diversion, bypass, or resection and associated cost, length of stay (LOS),
      morbidity, and mortality.  Forty-three patients undergoing palliative surgery
      were identified. The success of each approach was 80, 78, and 63 per cent for
      diversion, bypass, and resection, respectively. Major morbidity (63%), mortality
      (16%), and LOS (26 days) were greatest in those undergoing PR, but so was
      survival  (8.4 months). DS and IB had comparable morbidity (40 and 33%),
      mortality (10 and 0%), and LOS (25 and 21 days), but survival was shorter for DS
      (5.3 vs 6.5 months). Cost of PR was significantly greater ($79,000) than both DS
      ($36,000) and IB ($51,000). Escalation  in complexity of palliative measures for
      MBO results in improved survival but at significant cost both economically and
      physiologically. Quality of life should be discussed with patients when deciding
      how best to palliate their symptoms.

PMID- 22643259
TI  - Should compliance with the Surgical Care Improvement Project (SCIP) process
      measures determine Medicare and Medicaid reimbursement rates?
AB  - The Surgical Care Improvement Project (SCIP) is a project that focuses on
      improving surgical care by reducing surgical morbidity and mortality by 25 per
      cent by 2010. Starting in 2011, SCIP compliance affects Medicare and Medicaid
      reimbursement rates. Although SCIP reinforces better  practices in surgical care,
      does compliance with SCIP measures actually result in a decrease in surgical
      morbidity and mortality? This study examined compliance with the SCIP surgical
      site infection (SSI) module (prophylactic antibiotic received within 1 hour
      before surgical incision) during  2009 to 2010 (n = 703) to determine whether
      patients compliant with SCIP data had a correlation with SSI rates as reported by
      National Surgery Quality Improvement Program (NSQIP) data for the same time
      period. We found no statistically significant association in patients that have
      failed SCIP  INF1 in the years 2009 to 2010 (n = 43) and the rates of SSI (n = 0)
      for the same time period. These data suggest that SCIP compliance should not be
      used to determine Medicare and Medicaid reimbursement rates because there is no
      correlation between failure of SCIP INF1 and SSI. Instead, further  effort should
      be placed on developing tools designed to acknowledge outcome measures that
      result in decreased morbidity/mortality and change practices accordingly such as
      NSQIP.

PMID- 22643260
TI  - Nocturnal violence: implications for resident trauma operative experiences.
AB  - Trauma centers face novel challenges in resource allocation in an era of cost
      consciousness and work-hour restrictions. Studies have shown that time of day and
      day of week affect trauma admission volume; however, these studies were performed
      in cold climates. Data from 2000 to 2010  at a Level I trauma center were
      reviewed. Demographic, injury severity, and injury timing from 23,827 trauma
      patients were analyzed along with their emergency department disposition
      (operating room, intensive care unit, ward) and final outcome. Nighttime arrivals
      (NAs) accounted for 56.6 per  cent and daytime arrivals accounted for 43.4 per
      cent of total admissions. The increase in NAs was most pronounced during the
      period from midnight to 6 am on weekends (P < 0.05). Also, the period from
      midnight to 6 am on weekends showed a significantly increased proportion of
      penetrating  trauma (P < 0.01). Similarly, there was an increased rate of trauma
      arrivals needing emergent operative intervention in the period between midnight
      and 6 am on weekends when compared with any other time period (P < 0.01). In a
      southern Level I trauma center, patient volume  varies nonrandomly with time.
      Emergent operative intervention is more likely between midnight and 6 am, the
      peak time for penetrating trauma. Because resident operative experience is
      maximized at night and on weekends, coverage during these periods should remain a
      priority for residency programs.

PMID- 22643261
TI  - Effectiveness of thoracoscopic truncal vagotomy in the treatment of marginal
      ulcers after laparoscopic Roux-en-Y gastric bypass.
AB  - Marginal ulcer is a significant complication of laparoscopic Roux-en-Y gastric
      bypass (LRYGB). Most marginal ulcers resolve with medical management, but
      nonhealing ulcers may require revision of the gastrojejunostomy, a procedure with
      significant morbidity and mortality. Traditionally,  surgical therapy for
      refractory peptic ulcers includes a vagotomy. The current study evaluates the
      effectiveness of thoracoscopic truncal vagotomy (TTV) in the management of
      refractory marginal ulcers. All patients at two institutions with an intractable
      marginal ulcer after LRYGB treated  with TTV between 2003 and 2010 were reviewed.
      Data were collected from chart review and telephone interview. Seventeen patients
      (mean age, 39 +/- 13 years; 16 females) were diagnosed with marginal ulceration a
      median of 18 months after LRYGB and proceeded to TTV at a mean of 39 +/-  43
      weeks (range, 1 to 114 weeks) after the diagnosis. The median operative time was
      89 +/- 65 minutes (range, 45 to 318 minutes). Four patients had a complication
      (sympathetic contralateral pleural effusion, pneumothorax, operative bleeding,
      and readmission for emesis). Eleven patients  had follow-up of 3 months to 6
      years (median, 7 months). Nine patients (82%) had symptomatic improvement and/or
      endoscopic resolution, whereas two (18%) did not. No patient had endoscopic
      evidence of persistent or recurrent marginal ulcer. TTV achieves symptomatic
      improvement and/or endoscopic  resolution of intractable marginal ulcers in over
      80 per cent of patients status post gastric bypass and therefore offers a less
      morbid alternative to revision of the gastrojejunostomy.

PMID- 22643262
TI  - The predictive value of micrometastasis in nonsentinel lymph nodes.
AB  - The rate of micrometastatic disease (MMD) to nonsentinel lymph nodes (NSLNs) has
      been shown to vary considerably in the literature. We identified patients with
      breast cancer with MMD (N1mi) and measured the incidence of NSLN involvement. We
      then compared these patients with those who  had no metastasis to the SLN (N0)
      and those who had macrometastasis to the SLN (N2) in an attempt to better
      understand the behavior of patients with N1mi positivity. A retrospective
      analysis was conducted on 574 patients with invasive breast cancer between
      January 2000 and December 2007. Patients  were stratified into three groups: no
      metastasis (N0), MMD (N1mi), and macrometastasis (N2). Chi square analysis and
      logistic regression models using SPSS software were applied to determine
      significance between groups. MMD rate was 7.7 per cent (44 of 574). Of this
      subset of patients, 33 underwent  completion axillary dissection, and only two
      were found to have NSLN-positive disease. Statistical significance was achieved
      for NSLN positivity when comparing all three nodal groups against one another
      (chi(2)(2, 572) = 337.084, P = 0.000). Logistic regression showed  multifocality
      and lymphovascular invasion to be significant predictors of NSLN metastasis. NSLN
      positivity in patients with MMD acts similarly to node-positive disease and
      therefore cannot completely exclude axillary dissection from therapeutic
      algorithm.

PMID- 22643263
TI  - Repeat computed tomography for trauma patients undergoing transfer to a Level I
      trauma center.
AB  - Our goal was to determine the characteristics of trauma transfer patients with
      repeat imaging. A retrospective trauma registry review was performed to evaluate
      trauma patients who were transferred from referring institutions between January
      2005 and December 2009. Patients were divided  into those who had a duplicate
      computed tomography (CT) scan versus those who did not. There were 2678 patients
      included of whom 559 (21%) had at least one repeat CT scan, whereas 2119 (79%)
      did not have any repeat CT scans. Those with repeat CT scans were older (42.3 +/-
      27.3  years vs 37.3 +/- 25.6 years), had a higher Injury Severity Score (ISS)
      (13.7 +/- 8.7 vs 11.9 +/- 8.8), and more likely to have blunt trauma (odds ratio,
      4.7; confidence interval, 2.3 to 9.6) (P for all < 0.0007). Those with CT scans
      done only at the  referring facility were younger, had a lower ISS, and shorter
      lengths of stay (P for all < 0.0003). ISS and age were independent predictors for
      repeat CT scans. Transfer patients had imaging repeated one-fifth of the time.
      The younger, less injured patient went without repeat imaging  suggesting that
      they may have been adequately cared for at the outside institution.

PMID- 22643264
TI  - Outcomes after massive transfusion in nontrauma patients in the era of damage
      control resuscitation.
AB  - There are little data regarding the use of massive transfusion protocols (MTP)
      outside of the trauma setting. This study compares the use of an MTP between
      trauma and non-trauma (NT) patients. Data were collected for trauma and NT
      patients from the prospectively maintained MTP database  at a Level I trauma
      center over a 4-year period. Massive transfusion was defined as >= 10 units
      packed red blood cells (PRBCs) in a 24-hour period. Of 439 MTP activations, 37
      (8%) were NT patients (64% male; mean age = 51 years, initial base deficit = 
      10.8). Activations were for gastrointestinal  bleeding (n = 18), bleeding during
      surgery (n = 13), obstetrical complications (n = 5), and ruptured aortic aneurysm
      (n = 1). Over-activation of MTP (<10 units PRBCs/24 hours) was higher in NT than
      trauma patients (19/37, 51% vs 118/284, 29%, P < 0.01). For massive transfusion 
      patients, 24-hour mortality was higher in NT compared with trauma patients
      (10/17, 59% vs 100/284, 35%, P = 0.05), but there was no difference in 30-day
      mortality (10/17, 59% vs 144/284, 51%, P = 0.51). With over-activation in 51% of
      NT patients, MTP usage outside  of trauma is inefficient. Outcomes in NT patients
      were worse than trauma patients, which may be related to the underlying disease
      processes.

PMID- 22643265
TI  - Bariatric surgery is associated with a reduced risk of mortality in morbidly
      obese patients with a history of major cardiovascular events.
AB  - Although the safety of bariatric surgery in patients with established
      cardiovascular disease has been demonstrated, little is known about the mid- to
      long-term survival of these patients after surgery. We conducted a retrospective
      cohort study of bariatric surgical patients (n = 349)  compared with morbidly
      obese surgical controls (n = 903). Data were obtained on all patients 40 to 79
      years of age, from 1996 to 2008, with a diagnosis code of morbid obesity, a
      primary surgical procedure of interest, and a cardiovascular event history. Data
      sources were the statewide South  Carolina UB92 inpatient hospitalization
      database and death records. The primary outcome was all-cause mortality. A total
      of 349 bariatric and 903 control patients with cardiovascular event histories
      were identified. Among bariatric patients, 19 deaths occurred in 986 person-years
      of follow-up  versus 150 deaths among controls in 3138 person-years of follow-up.
      Unadjusted all-cause mortality was estimated at 7 +/- 2 per cent at 5 years in
      bariatric patients compared with 19 +/- 2 per cent (P < 0.001) in controls.
      Adjusting for age, comorbidities, and event  history, the relative risk of
      mortality was reduced by 40 per cent in bariatric patients compared with controls
      [hazard ratios (95% confidence interval): 0.60 (0.36, 0.99)]. In patients with a
      history of cardiovascular events, bariatric surgery is associated with a
      significantly decreased  risk of all-cause mortality.

PMID- 22643266
TI  - Response to neoadjuvant chemotherapy in the breast predicts axillary nodal
      status.
AB  - We hypothesize that the diminishing role of axillary node dissection (ALND) in
      early stage breast cancer could be further reduced in patients with advanced
      disease depending on the response to neoadjuvant chemotherapy (NC). We reviewed
      records of patients managed with NC and recorded  demographics, tumor
      characteristics, pre/postoperative axillary nodal status, and NC response. We
      define a response to NC as follows: T2 tumors at least a 50 per cent reduction in
      the product of the length and width of the tumor and in T3-4 tumors a reduction
      in tumor size to less than  2 cm. We defined a negative axillary nodal status as
      either a negative sentinel node biopsy before or after NC or a negative ALND. We
      defined a positive axillary nodal status as clinical persistence of nodal disease
      despite NC or involved nodes determined by ALND. Fisher's exact test was used  to
      evaluate the association between response to NC and nodal status. Over the past 4
      years, 35 patients have completed NC and surgical treatment including lymph node
      assessment. Sixteen cancers demonstrated a response to NC and two (12.5%) had
      positive lymph nodes. Nineteen cancers failed  to respond to NC and 13 (68.4%)
      had involved lymph nodes. Fisher's exact test shows a strong association between
      NC response and nodal status (two-tailed P value 0.0016). Patients with advanced
      locoregional breast cancer that respond to NC are unlikely to benefit from ALND.
      If this  study's findings are confirmed in larger trials, ALND could be limited
      to patients with advanced locoregional breast cancer unresponsive to NC.

PMID- 22643267
TI  - Body composition analysis in bariatric surgery: use of air displacement
      plethysmograph.
AB  - Body weight, body mass index (BMI), and percent excess weight loss are used to
      assess patient outcomes after bariatric surgery; however, they provide little
      insight into the true nature of the patient's weight loss. Body composition
      measurements monitor fat versus lean mass losses  to permit interventions to
      reduce or avoid lean body mass loss after bariatric surgery. A retrospective
      review of patients who underwent bariatric surgery between 2002 and 2008 was
      performed. Patients underwent body composition testing via air displacement
      plethysmography before and after  surgery (6 and 12 months). Body composition
      changes were assessed and compared with the BMI. Results include 330 patients (54
      male, 276 female). Average preoperative weight was 139 kg, BMI was 50 kg/m(2),
      fat percentage was 55 per cent, and lean mass percent was 45 per cent. Twelve 
      months after surgery average weight was 90 kg, mean BMI was 32 kg/m(2), fat
      percentage was 38 per cent, and lean mass percent was 62 per cent. Body
      composition measurements help monitor fat losses versus lean mass gains after
      bariatric surgery. This may give a better assessment  of the patient's health and
      metabolic state than either BMI or excess weight loss and permits intervention if
      weight loss results in lean mass losses.

PMID- 22643268
TI  - Epitrochlear sentinel lymph nodes in melanoma: interval or independent?
AB  - Most primary melanomas on the distal upper extremity metastasize to a sentinel
      lymph node (SLN) in the axillary basin, but occasionally a primary melanoma will
      drain to the epitrochlear basin. The relationship between tumor-draining axillary
      and epitrochlear SLNs is unclear. We hypothesize  that the epitrochlear SLN
      functions in an interval manner with the axillary lymph node basin. We queried
      our melanoma database to identify patients who underwent SLN biopsy for a distal
      upper-extremity melanoma. Patient demographics, tumor characteristics, patterns
      of nodal drainage, and incidence  of SLN metastasis were analyzed. Of 255
      patients identified, 38 (14.9%) had an epitrochlear SLN. Mean Breslow thickness
      was 2.26 mm. All patients with epitrochlear drainage had concurrent axillary
      drainage and underwent axillary and epitrochlear SLN biopsies. Of these 38
      patients, two (5.2%)  had epitrochlear and axillary SLN metastasis, four (10.5%)
      had epitrochlear metastasis only, four (10.5%) had axillary metastasis only, and
      the remaining 28 (73.7%) had tumor-free SLNs. The invariable association of
      epitrochlear and axillary drainage in this study suggests that epitrochlear 
      nodes function in an interval role with the axillary lymph node basin. Therefore
      we recommend that all patients with a positive epitrochlear SLN undergo
      completion axillary dissection.

PMID- 22643269
TI  - The impact of implementation of the Bethesda System for Reporting Thyroid
      Cytopathology on the surgical treatment of thyroid nodules.
AB  - Published data suggest that the Bethesda System for Reporting Thyroid
      Cytopathology (BSRTC) is valuable in directing therapy of thyroid nodules.
      Literature examining the effect of the BSRTC on management when compared with pre
      BSRTC is lacking, however. This study evaluates the impact  of applying the BSRTC
      retrospectively to a series of patients who underwent surgery after a fine-needle
      aspiration biopsy (FNAB) classified using the pre BSRTC system, and investigates
      how the BSRTC application to the same population would have ultimately affected
      the management strategy.  One hundred patients who had previously undergone both
      FNAB and thyroidectomy before implementation of the BSRTC were randomly selected.
      Each FNAB was examined by a single cytopathologist (blinded to both the original
      interpretation and the surgical pathology findings) and reclassified using  the
      BSRTC. Accuracy of both systems was examined using the final pathology as the
      true diagnosis. Of 68 FNABs initially classified as indeterminate, 32 (47.1%)
      were reclassified as benign. There was no significant difference in overall rates
      of detection of malignancy on final pathology in  specimens classified as benign,
      both pre and post application of the BSRTC (P = 0.70). Application of the BSRTC
      resulted in a significant percentage of indeterminate specimens being
      reclassified as benign, presumably due to more standardized criteria for
      interpretation and reporting.  No significant change in detection of malignancy
      was observed. We conclude that application of the BSRTC may result in lower rates
      of thyroidectomy, while preserving the same diagnostic accuracy in the detection
      of thyroid malignancy.

PMID- 22643270
TI  - Old and undertriaged: a lethal combination.
AB  - The geriatric trauma patient poses unique challenges to the trauma surgeon due to
      occult injuries and occult hypoperfusion. We hypothesized that those elderly
      patients with significant injuries, who were not initially evaluated via trauma
      activation, would suffer worse outcomes. All  cases of elderly (age >= 65)
      admitted to the trauma service from the years 2000 to 2010 were included. Our
      trauma activation system encompasses anatomic, physiologic, and mechanism of
      injury criteria. We defined patients as undertriaged (UT) if they had an ISS > 15
      and did not undergo  a trauma team activation, but had a regular workup by an
      emergency department physician and trauma team consultation. Factors that
      contributed to being UT in the emergency department were investigated by
      univariate and multivariate analysis. A total of 4534 elderly patients constitute
      this  analysis, of which 15.1 per cent were UT. The UT patients were more likely
      to die, when adjusted for Revised Trauma Score, Glasgow Coma score, the
      occurrence of >=1 complication, and whether the patient was on Coumadin. UT has a
      high risk of death in elderly patients. Trauma triage guidelines  need to be
      better tailored to identify the high-risk geriatric trauma patient.

PMID- 22643271
TI  - Computerized tomography in the workup of pediatric appendicitis: why are children
      scanned?
AB  - Physicians increasingly use computerized tomography (CT) for the evaluation of
      suspected acute appendicitis (AA) in children despite increasing awareness of the
      potential dangers of CT-associated radiation exposure. Many studies demonstrate
      the value of CT in the diagnosis of AA, but  none have determined what factors
      influence the decision to perform a CT. We investigated factors associated with
      the use of CT during initial workup of children who subsequently underwent
      appendectomy. This is a retrospective review of all patients aged 0 to 17 years
      who underwent appendectomy  for AA by pediatric surgeons over 11 years. Both
      univariate and multivariable logistic regression models were created to predict
      use of CT. A total of 546 children underwent appendectomy for AA, of which 293
      (53%) underwent CT. In univariate analysis, seven variables were significantly
      associated  with the use of CT: female gender, Hispanic ethnicity, initial
      presentation to referring hospitals, lower Alvarado scores, delays from onset of
      symptoms to hospital presentation, migration, and rebound tenderness. In
      multivariable analysis, four variables significantly independently predicted  the
      use of CT: initial presentation to a referring hospital [odds ratio (OR) 3.50),
      female gender (OR 1.49), increased latency from symptom onset to presentation (OR
      1.34), and the presence of rebound tenderness (OR 0.23), which had a protective
      effect; the overall model was statistically  significant (P < 0.0001). This model
      is the first to define variables that significantly predict CT utilization in the
      pediatric population. Continued investigation will be necessary to develop
      effective algorithms for judicious use of CT for suspected AA.

PMID- 22643272
TI  - Surgery after colonic stenting.
AB  - Colonic stenting is an accepted treatment of large bowel obstruction. The
      literature is sparse regarding surgical difficulties associated with an
      indwelling stent. We report our experience focusing on outcomes, complications,
      and whether the stent created intraoperative concerns. In  this retrospective
      review, 6 patients were identified between 2007 and 2010 that had surgery after
      colonic stents were placed. Their charts were reviewed to compare clinical
      variables, surgical procedures, outcomes, and complications. One obstruction was
      due to diverticulitis. The stent reobstructed,  leading to emergent transverse
      loop colostomy, and subsequent sigmoidectomy with stoma reversal. Four patients'
      obstructing masses were malignant. The final patient's stent was placed through a
      Hartmann's stump to drain a pelvic abscess. These 5 patients had no stent
      complications. Surgery  occurred an average of 9.8 weeks after stent placement;
      four had low anterior resections and one underwent Hartmann's reversal. All 6
      patients had colorectal anastomoses and five underwent laparoscopic surgery; one
      had an anastomotic leak requiring reoperation. Colonic stenting allows for  the
      immediate relief of obstruction while permitting diagnosis and treatment of
      coexisting medical problems. The colon can be prepared for an elective rather
      than emergency operation, and a colostomy may be avoided.

PMID- 22643273
TI  - Unusual thrombotic complications.

PMID- 22643274
TI  - The mission? Reduce HAPUs.

PMID- 22643276
TI  - Got accountability? Increasing data transparency.

PMID- 22643277
TI  - Get authentically engaged.

PMID- 22643278
TI  - Quality improvement: Getting better all the time.

PMID- 22643280
TI  - Are certified nurses better professionals?

PMID- 22643281
TI  - Patient-care assistants, advanced.

PMID- 22643282
TI  - Quick tips for nurse educators.

PMID- 22643283
TI  - Go-live: Bedside nurses and informatics.

PMID- 22643284
TI  - What can you do when work isn't working?

PMID- 22643285
TI  - Embracing change: Healthcare technology in the 21st century.

PMID- 22643286
TI  - Why can't we all just get along?

PMID- 22643287
TI  - Novel insights into the phylogenetic relationships of the endangered marsupial
      genus Potorous.
AB  - The three extant potoroo species of the marsupial genus Potorous -Potorous
      tridactylus, P. longipes and P. gilbertii - are all of conservation concern due
      to introduced predators and habitat loss associated with the European settlement
      of Australia. Robust phylogenies can be useful to inform conservation management,
      but past phylogenetic studies on potoroos have been unable to fully resolve
      relationships within the genus. Here, a multi-locus approach was employed, using
      three mitochondrial DNA (mtDNA): NADH dehydrogenase subunit 2, cytochrome c
      oxidase subunit 1 and 12S rRNA and four nuclear DNA (nuDNA) gene regions: breast
      and ovarian cancer susceptibility gene, recombination activating gene-1,
      apolipoprotein B and omega globin. This was coupled with widespread geographic
      sampling of the broadly distributed P. tridactylus, to investigate the
      phylogenetic relationships within this genus. Analyses of the mtDNA identified
      five distinct and highly divergent lineages including, P. longipes, P. gilbertii
      and three distinct lineages within P. tridactylus (northern mainland, southern
      mainland and Tasmanian). P. tridactylus was paraphyletic with the P. gilbertii
      lineage, suggesting that cryptic taxa may exist within P. tridactylus. NuDNA
      sequences lacked the resolution of mtDNA. Although they resolved the three
      currently recognised species, they were unable to differentiate lineages within
      P. tridactylus. Current management of P. tridactylus as two sub-species (mainland
      and Tasmania) does not recognise the full scope of genetic diversity within this
      species, especially that of the mainland populations. Until data from more
      informative nuDNA markers are available, we recommend this species be managed as
      the following three subspecies: Potorous tridactylus tridactylus (southern
      Queensland and northern New South Wales); Potorous tridactylus trisulcatus
      (southern New South Wales and Victoria) Potorous tridactylus apicalis (Tasmania).
      Molecular dating estimated that divergences within Potorous occurred in the late
      Miocene through to the early Pliocene.

PMID- 22643288
TI  - Complete cpDNA genome sequence of Smilax china and phylogenetic placement of
      Liliales--influences of gene partitions and taxon sampling.
AB  - The complete nucleotide sequence of the chloroplast genome (cpDNA) of Smilax
      china L. (Smilacaceae) is reported. It is the first complete cp genome sequence
      in Liliales. Genomic analyses were conducted to examine the rate and pattern of
      cpDNA genome evolution in Smilax relative to other major lineages of monocots.
      The cpDNA genomic sequences were combined with those available for Lilium to
      evaluate the phylogenetic position of Liliales and to investigate the influence
      of taxon sampling, gene sampling, gene function, natural selection, and
      substitution rate on phylogenetic inference in monocots. Phylogenetic analyses
      using sequence data of gene groups partitioned according to gene function,
      selection force, and total substitution rate demonstrated evident impacts of
      these factors on phylogenetic inference of monocots and the placement of
      Liliales, suggesting potential evolutionary convergence or adaptation of some
      cpDNA genes in monocots. Our study also demonstrated that reduced taxon sampling
      reduced the bootstrap support for the placement of Liliales in the cpDNA
      phylogenomic analysis. Analyses of sequences of 77 protein genes with some
      missing data and sequences of 81 genes (all protein genes plus the rRNA genes)
      support a sister relationship of Liliales to the commelinids-Asparagales clade,
      consistent with the APG III system. Analyses of 63 cpDNA protein genes for 32
      taxa with few missing data, however, support a sister relationship of Liliales
      (represented by Smilax and Lilium) to Dioscoreales-Pandanales. Topology tests
      indicated that these two alignments do not significantly differ given any of
      these three cpDNA genomic sequence data sets. Furthermore, we found no saturation
      effect of the data, suggesting that the cpDNA genomic sequence data used in the
      study are appropriate for monocot phylogenetic study and long-branch attraction
      is unlikely to be the cause to explain the result of two well-supported, conflict
      placements of Liliales. Further analyses using sufficient nuclear data remain
      necessary to evaluate these two phylogenetic hypotheses regarding the position of
      Liliales and to address the causes of signal conflict among genes and partitions.

PMID- 22643289
TI  - Phylogenetic analysis of Primula section Primula reveals rampant non-monophyly
      among morphologically distinct species.
AB  - The type section of Primula (Primulaceae), here considered to include seven
      species, is phylogenetically quite isolated in its genus. Although its species
      are popular ornamentals, traditional medicinal plants and model organisms for the
      study of heterostyly, the section has not yet been studied from a phylogenetic or
      evolutionary perspective. Using phylogenetic analysis of nuclear ITS and plastid
      data from all species and subspecies, we find that widespread Primula elatior is
      genetically heterogeneous and non-monophyletic to most if not all of the other
      ingroup taxa. The Genealogical Sorting Index (GSI) indicates that the assumption
      of all currently accepted species being independent lineages is consistent with
      the data. It is possible that P. elatior in its current circumscription may
      represents the disjointed remnant of an ancestral species from which the other
      recognized species diverged. However, based on available data, the alternative
      possibility of introgression explaining the non-monophyly of this species cannot
      be excluded. Species trees show P. elatior and P. veris as sister species.
      Primula vulgaris and P. juliae are closely related, while, in contrast to
      previous assumptions, P. renifolia does not appear to be a close relative of P.
      megaseifolia. With the section's isolation from the rest of the genus and very
      short internal branches, our dataset also presents a case study of the
      confounding effects of different branch length priors on the Bayesian estimation
      of resulting branch length estimates. Experimental runs using different priors
      confirm the problem of resulting estimates varying by orders of magnitude, while
      topology and relative branch lengths seem unaffected.

PMID- 22643290
TI  - The challenge of defining relative adrenal insufficiency.

PMID- 22643291
TI  - Initial experience using Sivelestat to manage preterm labor with a bulging fetal
      membrane in pregnant women.
AB  - Intrauterine infection and inflammation are recognized as major contributors to
      the onset of preterm labor. We describe two cases of severe preterm labor with
      bulging membrane that were treated by intravenous injection of Sivelestat, a
      neutrophil elastase inhibitor. Ritodrine hydrochloride and magnesium sulfate were
      intravenously administered for tocolysis, and ampicillin was provided as an
      antibiotic. Urinary trypsin inhibitor (UTI) was administered transvaginally.
      Sivelestat was infused intravenously at 4.8 mg kg(-1) day(-1) through the
      maternal vein. No side effects were observed. Levels of interleukin (IL)-6 and IL
      8 in amniotic fluid decreased, and gestations were prolonged without
      complications for >1 week. Two healthy infants were delivered. Our experience
      suggests that multidrug therapy with Sivelestat offers a new therapeutic strategy
      for preterm labor, but further investigations of the indications, administration
      period and dosage are required.

PMID- 22643292
TI  - Hyperleukocytosis in a premature infant with intrauterine herpes simplex
      encephalitis.
AB  - Herpes encephalitis is a rare but devastating infection in premature infants. We
      report a 29 week gestation infant with severe intrauterine cutaneous and central
      nervous system herpes accompanied by hyperleukocytosis. Leukemoid reactions are
      not uncommon in this population, but the association of herpes encephalitis and a
      leukemoid reaction or hyperleukocytosis has not been reported previously.

PMID- 22643293
TI  - Persistent cerebral blood flow by transcranial Doppler ultrasonography in an
      asphyxiated newborn meeting brain death diagnosis: case report and review of the
      literature.
AB  - We want to illustrate the difficulty of establishing a brain death diagnosis in
      newborn children and how an easy and useful tool, the transcranial Doppler
      ultrasonography, can leave an unexpected result that complicates the process
      despite the rest of the diagnostic tests. We describe a 36-week gestation newborn
      male who was diagnosed of brain death after asphyxiated and offered for donation.
      After initial stabilization at admission, we established brain death diagnosis by
      checking and meeting every criterion. The donation process was complicated
      because of persistent blood flow on transcranial Doppler ultrasonography.
      Transcranial Doppler ultrasonography is a very useful method to assess cerebral
      blood flow. However, caution and individualization are needed when interpreting
      this complementary exam, especially in highly conflictive situations like brain
      death diagnosis.

PMID- 22643294
TI  - Thanatophoric dysplasia, type I.

PMID- 22643296
TI  - Feed thickeners and NEC: too risky to chance.

PMID- 22643297
TI  - Health inequalities among urban children in India: a comparative assessment of
      Empowered Action Group (EAG) and South Indian states.
AB  - As India rapidly urbanizes, within urban areas socioeconomic disparities are
      rising and health inequality among urban children is an emerging challenge. This
      paper assesses the relative contribution of socioeconomic factors to child health
      inequalities between the less developed Empowered Action Group (EAG) states and
      more developed South Indian states in urban India using data from the 2005-06
      National Family Health Survey. Focusing on urban health from varying regional and
      developmental contexts, socioeconomic inequalities in child health are examined
      first using Concentration Indices (CIs) and then the contributions of
      socioeconomic factors to the CIs of health variables are derived. The results
      reveal, in order of importance, pronounced contributions of household economic
      status, parent's illiteracy and caste to urban child health inequalities in the
      South Indian states. In contrast, parent's illiteracy, poor economic status,
      being Muslim and child birth order 3 or more are major contributors to health
      inequalities among urban children in the EAG states. The results suggest the need
      to adopt different health policy interventions in accordance with the pattern of
      varying contributions of socioeconomic factors to child health inequalities
      between the more developed South Indian states and less developed EAG states.

PMID- 22643298
TI  - Biological behavior of different Trypanosoma cruzi isolates circulating in an
      endemic area for Chagas disease in the Gran Chaco region of Argentina.
AB  - The biological behavior of the different Trypanosoma cruzi strains is still
      unclear and the importance of exploring the relevance of these differences in
      natural isolates is of great significance. Herein we describe the biological
      behavior of four T. cruzi isolates circulating sympatrically in a restricted
      geographic area in Argentina endemic for Chagas Disease. These isolates were
      characterized as belonging to the Discrete Typing Units (DTUs) TcI, TcIII, TcV
      and TcVI as shown by Multilocus Enzyme Electrophoresis and Multilocus Sequence
      Typing. In order to study the natural behavior of the different isolates and to
      preserve their natural properties, we developed a vector transmission model that
      allows their maintenance in the laboratory. The model consisted of serial
      passages of these parasites between insect vectors and mice. Vector-derived
      parasite forms were then inoculated in C57BL/6J mice and number of parasite in
      peripheral blood, serological response and histological damage in acute and
      chronic phases of the infection were measured. Parasites from DTUs TcI, TcIII and
      TcVI were detected by direct fresh blood examination, while TcV parasites could
      only be detected by Polimerase Chain Reaction. No significant difference in the
      anti-T. cruzi antibody response was found during the chronic phase of infection,
      except for mice infected with TcV parasites where no antibodies could be
      detected. Histological sections showed that TcI isolate produced more damage in
      skeletal muscle while TcVI induced more inflammation in the heart. This work
      shows differential biological behavior among different parasite isolates obtained
      from the same cycle of transmission, permitting the opportunity to formulate
      future hypotheses of clinical and epidemiological importance.

PMID- 22643299
TI  - Reliability and validity of individualized satisfaction score in aid for decision
      making in occupation choice.
AB  - PURPOSE: The iPad application aid for decision-making in occupation choice (ADOC)
      was developed to measure the client's satisfaction with individualized
      occupational performance of meaningful and purposeful activities. The present
      study examined the reliability and validity of individualized satisfaction
      measurement using the ADOC. METHOD: The Japanese version of the ADOC was used by
      36 occupational therapists on 92 of their clients (44 males, 48 females, mean age
      66.4 +/- 17.8 years). Convergent and discriminant validity were examined using
      Pearson's correlation between ADOC satisfaction score and the Life Satisfaction
      Index K (LSIK) factors: Factor 1 (satisfaction with life), Factor 2 (optimistic
      and positive disposition) and Factor 3 (evaluation of own aging). Test-retest
      reliability was assessed using the intraclass correlation coefficient (ICC).
      RESULTS: Ninety-two clients completed the validation study. Satisfaction with
      ADOC significantly correlated with LSIK Factor 1 (r = 0.297, p < 0.01), but not
      with Factors 2 or 3 (r = -0.045 and -0.089, respectively). Of the 92 clients, 78
      participated in the test-retest reliability study. Good to moderate correlation
      was revealed (ICC = 0.712, p < 0.001). CONCLUSIONS: The Japanese version of the
      ADOC is a valid and reliable instrument for measuring client satisfaction with
      individualized occupational performance.

PMID- 22643300
TI  - Positron range in PET imaging: an alternative approach for assessing and
      correcting the blurring.
AB  - Positron range impairs resolution in PET imaging, especially for high-energy
      emitters and for small-animal PET. De-blurring in image reconstruction is
      possible if the blurring distribution is known. Furthermore, the percentage of
      annihilation events within a given distance from the point of positron emission
      is relevant for assessing statistical noise. This paper aims to determine the
      positron range distribution relevant for blurring for seven medically relevant
      PET isotopes, (18)F, (11)C, (13)N, (15)O, (68)Ga, (62)Cu and (82)Rb, and derive
      empirical formulas for the distributions. This paper focuses on allowed-decay
      isotopes. It is argued that blurring at the detection level should not be
      described by the positron range r, but instead the 2D projected distance delta
      (equal to the closest distance between decay and line of response). To determine
      these 2D distributions, results from a dedicated positron track-structure Monte
      Carlo code, Electron and POsitron TRANsport (EPOTRAN), were used. Materials other
      than water were studied with PENELOPE. The radial cumulative probability
      distribution G(2D)(delta) and the radial probability density distribution
      g(2D)(delta) were determined. G(2D)(delta) could be approximated by the empirical
      function 1 - exp(-Adelta(2) - Bdelta), where A = 0.0266 (E(mean))(-1.716) and B =
      0.1119 (E(mean))(-1.934), with E(mean) being the mean positron energy in MeV and
      delta in mm. The radial density distribution g(2D)(delta) could be approximated
      by differentiation of G(2D)(delta). Distributions in other media were very
      similar to water. The positron range is important for improved resolution in PET
      imaging. Relevant distributions for the positron range have been derived for
      seven isotopes. Distributions for other allowed-decay isotopes may be estimated
      with the above formulas.

PMID- 22643301
TI  - In vitro determination of the CYP 3A4 activity in rat hepatic microsomes by
      liquid-phase extraction and HPLC-photodiode array detection.
AB  - INTRODUCTION: CYP3A4 is one of the most important of all drug-metabolizing
      enzymes. Although several direct or indirect quantification methods have been
      proposed for the determination of the CYP3A4 activity, the sample preparation is
      mostly tedious and usually requires time consuming separate extraction steps and
      solid-phase extraction. METHODS: Here, we developed a simple and selective HPLC
      method, coupled to photodiode array detection for direct determination of CYP3A4
      mediated testosterone hydroxylase activity in hepatic microsomes of rats. After
      microsome incubation, a single-step liquid-phase extraction of specific
      substrates, testosterone and its metabolite 6-hydroxytestosterone, together with
      the salicylamid acid used as an internal standard, was applied. The analytical
      method was fully validated by the determination of different parameters (intra-
      and inter-day variability of 6-beta-OH-testosterone concentration, accuracy and
      limit of detection). Finally, this method was applied to quantify the CYP3A4
      activity of rats intravenously administered with either the mesoporous iron(III)
      trimesate MIL-100 nanocarrier (MIL stands for Materials from Institut Lavoisier)
      or with its corresponding organic linker. RESULTS: All analytes were
      simultaneously separated from a single run shorter than 10 min, reaching relative
      standard deviations of intra- and inter-day precision <18.5% and an accuracy of
      estimated 6-beta-OH-testosterone concentrations ranging from 95 to 111%. The
      mean+/-standard deviation absolute recoveries of 6-beta-OH-testosterone at 0.01,
      1.00 and 20.00 MUg/mL were 97+/-4%, 101+/-3% and 99+/-2%, respectively while it
      reached 98+/-3% for the internal standard. DISCUSSION: The developed HPLC-PDA
      method enables the accurate and sensitive determination of the CYP3A4 activity
      through the quantification of the 6-beta-OH-testosterone produced by the CYP3A4
      mediated testosterone hydroxylase in rat hepatic microsomal suspensions.
      Additionally, the rapid procedure offers an economical advantage with respect to
      resources and operator time. Finally, the determination of CYP3A4 activity in
      hepatic microsomes of rats administered with nanoparticles of the porous
      iron(III) trimesate nanocarrier shows no significant differences between control,
      trimesic and nanoparticle groups, evidencing that the linker is not metabolized
      by CYP3A4.

PMID- 22643302
TI  - Development of residential care services facilitated for persons with dementia in
      Norway.
AB  - BACKGROUND: In the 1980s, special care units devoted to persons with dementia
      (SCU) were established, and in the 1990s, a new system of sheltered housing for
      persons with dementia (SH) was inaugurated. AIM: The aim of this study was to
      examine the establishment of SCUs and SH units and to explore the effects of
      varying patient-staff ratios and unit sizes. METHOD: On five occasions
      (1996/1997, 2000/2001, 2004/2005, 2008, 2010/2011), a detailed questionnaire was
      sent by post to all Norwegian municipalities. It contained questions about the
      provision of services for persons with dementia. RESULTS: In 1996/1997, 70% of
      the municipalities had SCUs and 13.3% of the beds in Norwegian nursing homes were
      in SCUs. In 2010/11, 87% of the municipalities had such services, which filled
      23.8% of the beds in nursing homes. The number of beds in SH units increased from
      856 beds in 1996/1997 to 2181 beds in 2010/11. SCUs have on average three
      patients per carer on an ordinary weekday day-time shift. These numbers have been
      quite stable throughout the study period. The ratio is about 3.5 patients per
      carer in the SH units and is also stable. CONCLUSIONS: The rate of increase in
      the provision of institutional beds facilitated for persons with dementia has
      been slow in Norway over the last 14 years. Both SCUs and SH units seem to have
      stable staffing ratios and the number of beds in each unit is also stable.

PMID- 22643303
TI  - Assessment of balance in unsupported standing with elderly inpatients by force
      plate and accelerometers.
AB  - BACKGROUND AND AIMS: Unsupported standing is one of the most important functional
      tasks involving balance control. Unlike younger people, who have been shown to
      counteract imbalance preferably with an ankle strategy, older people tend to do
      so with a hip strategy. These strategies can be described by matching balance
      measures at floor and hip level, a good match representing an ankle-dominant
      strategy and a low one a hip-dominant strategy. The aim of this study was to show
      possible change in the association between force platform measurement at floor
      level and accelerometry at hip level in elderly inpatients standing unsupported
      during rehabilitation. METHODS: Forty four elderly inpatients (mean age 82.5 yrs)
      after hip fracture or stroke were recruited for the study. Balance was assessed
      after admission and 2 weeks later on a force platform at floor level and
      simultaneously by a tri-axial accelerometer at hip level. RESULTS: The
      correlation between the 2 measures was initially poor to fair (r=0.04 to r=0.51),
      but increased after 2 weeks of rehabilitation (r=0.30 to r=0.66). CONCLUSIONS: A
      change in the association between measures obtained at lower back level and floor
      level may indicate a change from a hip- to an ankle-dominant strategy, to
      counteract imbalance during unsupported standing.

PMID- 22643304
TI  - Short Berg Balance Scale - correlation to static and dynamic balance and
      applicability among the aged.
AB  - BACKGROUND AND AIMS: To create a shorter version of the Berg Balance Scale (BBS)
      and to assess correlations between short BBS and static and dynamic aspects of
      balance among community-dwelling aged with a self-reported history of falling.
      METHODS: 519 (88%) subjects were included in the study, for whom BBS, and static
      and dynamic balance measurements were performed. Explanatory factor analysis was
      used to create a shorter version of the BBS. Static and dynamic balance was
      measured on a force platform. Correlations between the short BBS and static and
      dynamic balance were analysed by Spearman's correlation analysis. Cronbach's
      alpha was used to assess the internal consistency of the short BBS. RESULTS:
      Explanatory factory analysis produced two factors. Factor 1 consisted of nine
      items and factor 2 of four items of the BBS. One item of the original BBS was not
      loaded in these factors. The short BBS (BBS-9) was formed of factor 1. It
      correlated significantly with the original BBS, and had moderate correlations
      with static and dynamic aspects of balance (p<0.001). The high scores of BBS-9
      were associated with better static and dynamic balance. BBS-9 demonstrated as
      good internal consistency reliability (Cronbach's alpha [alpha]=0.69) as the
      original BBS (alpha=0.74). CONCLUSIONS: Results support the applicability of BBS
      9 in assessing functional balance among the aged with quite good physical
      function. However, more studies are needed to verify applicability to other
      samples and to assess cut-off scores for BBS-9, to predict the likelihood of
      falling.

PMID- 22643305
TI  - Prevalence, correlates and perceived causes of limitations in activities of daily
      living among older Singaporeans.
AB  - AIMS: To describe the prevalence of limitations in Activities of Daily Living
      (ADL) among older Singaporeans, examine the association of ADL limitations with
      various self-reported health conditions, assess perceived causes of ADL
      limitations, and compare prevalence of health conditions among those who perceive
      only 'old age' vs those who perceive at least one specific health condition as
      the cause of their limitations. METHODS: Data from a national survey of
      Singaporeans 60 years and over was used. The association between ADL limitations
      and health conditions was assessed through logistic regression. Those with ADL
      limitations were asked about the perceived cause/s of their limitation/ s. Any
      significant difference in the prevalence of health conditions between those
      attributing their ADL limitations only to old age and those attributing to at
      least one specific health condition was ascertained. RESULTS: Overall prevalence
      of ADL limitations was 9.7%. Joint/nerve pain, stroke, pelvic/femoral fractures,
      heart diseases, diabetes, osteoporosis, chronic respiratory illness and
      renal/urinary tract illness were significantly associated with ADL limitations,
      and the most common perceived cause was 'old age' (33%). The prevalence of most
      health conditions was similar in older adults attributing their limitations to
      only 'old age' and to at least one specific health condition. CONCLUSION:
      Clinical suspicion is called for if individuals with ADL limitations attribute
      them solely to 'old age'.

PMID- 22643306
TI  - Prediction of risk of in-hospital geriatric complications in older patients with
      hip fracture.
AB  - BACKGROUND AND AIMS: Hip fracture in older persons is a frequent reason for
      hospital admission and a substantial workload in orthopedic wards for geriatric
      liaison teams. However, robust patients who do not present in-hospital
      complications may not need geriatric liaison. For the sake of triage, we studied
      the ability of usual admission scores to identify patients who will not develop
      in-hospital complications, and who may therefore not be included in the
      overworked geriatric liaison teams. METHODS: A retrospective cohort of
      consecutive community- living elderly patients (age >= 75 yrs), admitted for
      traumatic hip fracture in the orthopedic divisions of a teaching hospital over 18
      months was examined. The predictive value of commonly used frailty scores (ISAR,
      VIP, KATZ) to rule out the incidence of three frequent and preventable in
      hospital acute geriatric events (major behavioral problems, pressure sores,
      falls) was assessed by ROC curves and negative likelihood ratio (-LR). RESULTS:
      Of 145 older persons with hip fracture (median age 84 years; 76% women; 57%
      living alone, 44% with pre-existing geriatric syndromes), 81 (56%) presented some
      acute geriatric events (AGE), i.e. major behavioral problems (46%), pressure
      sores (19%) and/or falls (5%). The three frailty admission scores showed low
      power for AGE prediction (area under the ROC curve: 53- 58%) and identification
      of patients who will not present in-hospital AGE (-LR>0.5 at the most sensitive
      cut-off). CONCLUSIONS: None of the three scores helped in the triage of patients
      according to their risk of future in-hospital AGE. All older patients with hip
      fracture, irrespective of their admission frailty-robustness profile, should
      receive geriatric evaluation and intervention.

PMID- 22643307
TI  - Physical function and perceived quality of life in older persons.
AB  - BACKGROUND AND AIMS: Physical function and quality of life represent two major
      components of multidimensional evaluation in older people. The aim of the study
      was to verify which specific physical function measure is a more important
      predictor of quality of life in these individuals. METHODS: Data are from 73
      community-dwelling older persons attending a geriatric cardiovascular clinic.
      Linear regressions and analyses of covariance were performed to explore the
      relationships between physical function measures (4-meter walking test [4mWS],
      Short Physical Performance Battery [SPPB], Activities of Daily Living [ADL], and
      Instrumental ADL [IADL]) and quality of life (assessed using the European Quality
      of Life [EuroQoL] instrument). To provide fair comparisons across all the
      physical function measures, results were provided according to their increase in
      standard deviation (SD). RESULTS: The mean age of the sample population (women
      52%) was 77.6 (SD=8.3) years old. Given significant gender interactions between
      physical function and quality of life, separate analyses were conducted for men
      and women. In women, all physical function measures were significantly associated
      with quality of life measures in unadjusted models (p-values<0.05). The EuroQoL
      visual analogic scale maintained its significant associations with SPPB, ADL and
      IADL, even after adjustment for potential confounders. In men, no physical
      function measure was consistently associated with quality of life in the fully
      adjusted models. Gender-specific differences in the perception of quality of life
      were reported for disabilities in specific IADL tasks. CONCLUSIONS: Physical
      function is associated with quality of life in older persons. In particular,
      disabilities in some specific IADL tasks seem to be especially perceived by women
      as undermining their quality of life. The use of the IADL scale in men may not be
      as reliable as in women.

PMID- 22643308
TI  - Broken heart in elderly patients: two clinical observations.
AB  - Tako-tsubo cardiomyopathy (idiopathic or transient left ventricular apical
      ballooning syndrome [ABS]) is a reversible condition frequently precipitated by a
      stressful trigger that clinically mimics an acute ST-elevation myocardial
      infarction. Characteristically, hypokinesis or akinesis occurs in the mid- and
      apical segments of the left ventricle in the absence of epicardial coronary
      lesions. Preserved or hyperdynamic function of the basal myocardial segments
      results in apical ballooning, assuming the shape of a Japanese pot used to catch
      octopus (a takotsubo). We report on 2 well over 70 years old women (78 and 82
      years) admitted to the emergency room with chest pain. Clinical signs, ECG
      alterations and high troponin I in both patients imposed urgent diagnostic
      testing and management. The electrocardiographic findings were consistent with
      acute myocardial infarction and transthoracic echocardiography showed in both
      simultaneous apical akinesia and a hyperkinetic basal area with a moderately
      reduced left ventricular ejection fraction. Coronary angiography, performed on an
      emergency basis, in both cases revealed minimal luminal irregularities, with no
      evidence of plaque rupture or thrombus. The wall motion abnormality extended
      beyond the distribution of any single coronary artery, making it less likely that
      an occlusive thrombus had spontaneously dissolved or that intermittent vasospasm
      had occurred. Taken together, these findings were consistent with ABS, and
      critical observations on coronary angiography indicated the diagnosis by
      exclusion. The patients were seen in the clinic 4 weeks after discharge. They had
      had no recurrent chest pain, and had returned to the normal life they had had
      before the cardiovascular event. A repeat echocardiography showed a normalized
      estimated ejection fraction in both patients. ABS is a diagnosis of exclusion and
      its incidence is probably underestimated in elderly patients in whom coronary
      angiography is not common.

PMID- 22643309
TI  - Clinical characteristics of population referred to an Italian center for
      dementia.

PMID- 22643310
TI  - Reflections by an American on being a visiting professor in Italy.

PMID- 22643311
TI  - Preclinical evaluation of 227Th-labeled and 177Lu-labeled trastuzumab in mice
      with HER-2-positive ovarian cancer xenografts.
AB  - OBJECTIVE: The aim of the present study was to compare the biodistribution,
      normal tissue toxicity, and therapeutic effect of two low-dose rate
      radioimmunoconjugates (RICs) in mice with HER2-expressing ovarian cancer
      xenografts: the alpha-particle-emitting (227)Th-trastuzumab and the beta-particle
      emitting (177)Lu-trastuzumab. MATERIALS AND METHODS: Trastuzumab (Herceptin),
      conjugated to DOTA and radiolabeled with (227)Th or (177)Lu, was injected
      intravenously into mice bearing SKOV-3 xenografts. The biodistribution was
      determined at different time points after injection. The organs were collected
      and measured for radioactivity content using a gamma spectrometer. Inhibition of
      tumor growth was measured after a single injection of (227)Th-trastuzumab,
      (227)Th-rituximab, (177)Lu-trastuzumab, trastuzumab alone, and NaCl. The toxicity
      of (227)Th-trastuzumab and (177)Lu-trastuzumab was evaluated by measurement of
      body weight, determination of blood cell counts, analysis of clinical chemistry
      parameters, and histological examination of tissue specimens. RESULTS: The
      absorbed radiation dose to the tumor was 4 Gy after administration of 400 kBq/kg
      (227)Th-trastuzumab and 72 MBq/kg (177)Lu-trastuzumab. A significantly better
      antitumor effect of (227)Th-trastuzumab (8 and 30 days' growth delay for 400 and
      600 kBq/kg, respectively) was observed as compared with untreated control,
      trastuzumab alone, 600 kBq/kg (227)Th-rituximab (nonspecific targeting), and 72
      MBq/kg (177)Lu-trastuzumab. Mean survival of mice after treatment with (227)Th
      trastuzumab (107 +/- 9 and 129 +/- 12 days for 400 and 600 kBq/kg (227)Th
      trastuzumab, respectively) was significantly improved compared with control (88
      +/- 11 days) and other RICs (85 +/- 8 and 66 +/- 6 days for 72 MBq/kg (177)Lu
      trastuzumab and 600 kBq/kg (227)Th-rituximab, respectively) (P<0.05, Kaplan
      Meier). Treatment-related toxicity was not observed in any group except for a
      transient decrease in white blood cells between 3 and 9 weeks after treatment
      with 400 and 600 kBq/kg (227)Th-trastuzumab. CONCLUSION: The alpha-particle
      emitting RIC (227)Th-trastuzumab effectively delayed tumor growth and prolonged
      survival of mice compared with beta-emitting (177)Lu-trastuzumab administered at
      the same absorbed radiation dose to tumor. This new therapeutic approach warrants
      further studies aiming at clinical testing in patients with micrometastatic
      ovarian cancer.

PMID- 22643313
TI  - Objective assessment of learning curves for the Voxel-Man TempoSurg temporal bone
      surgery computer simulator.
AB  - INTRODUCTION: Simulators are becoming an increasingly important part of surgical
      training. Temporal bone surgery is one area in which simulators, such as the
      Voxel-Man TempoSurg simulator, are likely to play a significant role in training.
      We present learning curve data from novice trainees using this simulator to learn
      cortical mastoidectomy, exposure of the sigmoid sinus, and exposure of the short
      process of the incus. METHODS: We measured the time taken to perform the
      procedures, the volume of reference bone removed, and the structures damaged
      during dissection. RESULTS: We found improvement in a number of parameters over
      the course of the study. The overall scores, structural damage scores and time
      taken improved, to differing degrees, for each task. The volume of reference bone
      removed remained constant. CONCLUSION: These results indicate that the trainees'
      efficiency improved as they became more proficient at removing a given volume of
      reference bone.

PMID- 22643314
TI  - Radiolabeling of folate targeted multifunctional conjugate with Technetium-99m
      and biodistribution studies in rats.
AB  - Despite the progress in the diagnosis and management of early stage disease, the
      management of advanced prostate cancer remains an important problem. Prostate
      tissue expresses folate receptor (FR) which binds both folic acid and folate
      linked drugs or imaging agents. Doxorubicin is the best known and most widely
      used member of the anthracycline antibiotic group of anticancer agents. The aim
      of this work is to develop a multifunctional nanoconjugate, (99m)Tc-folate-PEG
      doxorubicin, in order to investigate its radiopharmaceutical potential as a
      prostate cancer imaging and real-time drug location imaging agent. Through this
      aim, biodistribution studies of (99m)Tc-folate-PEG-doxorubicin and control groups
      ((99m)Tc-doxorubicin and (99m)Tc-PEG-doxorubicin) in male rats were carried out.
      Obtained data showed that uptake of (99m)Tc-folate-PEG-doxorubicin in prostate
      was significantly higher than that of the control groups due to the affinity of
      folate ligand to folate receptor. As a consequence, it was indicated that (99m)Tc
      FOL-PEG-DOX radiolabeled conjugate which has a great target/non-target organ
      ratio, is specific for target organ and has a high radiopharmaceutical potential
      as a prostate cancer and real-time drug location imaging agent.

PMID- 22643315
TI  - Tamoxifen-loaded novel liposomal formulations: evaluation of anticancer activity
      on DMBA-TPA induced mouse skin carcinogenesis.
AB  - PURPOSE: Tamoxifen (TAM) is a non-steroidal estrogen receptor modulator known for
      its anticancer activity. Apart from marked breast cancer activity, this drug has
      also shown potential in treating other types of cancers including skin cancers.
      TAM is reported to be associated with serious side effects primarily due to its
      systemic distribution. The localized delivery of this drug in this regard would
      be highly beneficial with respect to safety as well as efficacy. METHODS: In the
      current studies, an endeavor has been made to investigate the efficacy of
      topically applied liposome-encapsulated TAM on skin cancer model. The drug was
      encapsulated in phospholipid-based vesicular systems viz. conventional liposomes
      and elastic liposomes. Incidence of papillomas and histopathological examination
      were employed to determine the efficacy of the tested formulations. RESULTS: The
      results demonstrated carrier-dependent strong inhibition of skin carcinogenesis
      with encapsulated drug vis-a-vis drug in the solution form. The encouraging
      findings from the current work construe immense potential of the TAM-loaded
      liposomal systems in the management of skin cancer.

PMID- 22643316
TI  - IgA antibodies against deamidated gliadin peptides in patients with chronic liver
      diseases.
AB  - BACKGROUND/AIMS: IgA antibodies against tissue-transglutaminase (anti-tTG-IgA)
      and IgA and IgG antibodies against deamidated gliadin peptides (anti-DGP-IgA and
      anti-DGP-IgG) are considered specific for celiac disease (CD) whereas, patients
      with chronic liver disorders have an increased risk of latent CD development. We
      investigated the prevalence and clinical significance of anti-DGP-IgA, anti-DGP
      IgG and anti-tTG-IgA in a large cohort of patients with chronic liver diseases.
      METHODS: 668 patients without gastrointestinal symptoms (426 viral hepatitis, 94
      autoimmune liver diseases, 61 alcoholic disease, 46 non-alcoholic fatty liver
      disease, 41 with other liver disorders) were investigated by ELISAs (INOVA
      Diagnostics). Patients positive for at least one autoantibody invited for a small
      intestinal biopsy and HLA-DQ typing. RESULTS: Anti-DGP-IgA were detected in 8.5%,
      anti-DGP-IgG in only one (0.15%, P<0.001) and anti-tTG-IgA in 5.8% of patients
      (P=0.05). Fifty-two were anti-DGP-IgA(+)/anti-tTG-IgA(-), 34 anti-DGP-IgA(-)/anti
      tTG-IgA(+), and 5 anti-DGP-IgA(+)/anti-tTG-IgA(+). Anti-DGP-IgA positivity was
      associated with older age (P<0.05), cirrhosis (P<0.05) and increased IgA (P<0.05)
      whereas, anti-tTG-IgA only with cirrhosis (P<0.05). Histology and HLA-typing
      compatible with CD was revealed in 4/14 anti-DGP-IgA(+)/anti-tTG-IgA(-), 0/13
      anti-DGP-IgA(-)/anti-tTG-IgA(+) and 2/2 anti-DGP-IgA(+)/anti-tTG-IgA(+). All 6
      patients diagnosed with CD were anti-DGP-IgA(+) and only 2 anti-tTG-IgA(+).
      CONCLUSIONS: Although a significant number of patients had detectable CD-related
      autoantibodies, anti-DGP-IgA test seems better than anti-tTG-IgA for unmasking
      occult forms of CD in patients with chronic liver disorders. The known good
      performance for CD diagnosis of anti-DGP-IgG test was not confirmed in this
      specific group of patients.

PMID- 22643317
TI  - Phase-dependent respiratory-motor interactions in reaction time tasks during
      rhythmic voluntary breathing.
AB  - The study investigated squeezing reaction time (RT) in response to a visual cue
      during rhythmic voluntary breathing at 0.6 Hz paced by a metronome, breath
      holding, or at rest in 13 healthy subjects. Rhythmic voluntary breathing slowed
      down RT, only in the expiratory phase with accompanied changes in the length of
      respiratory phases, while breath-holding reduced RT. The prolonged RT during
      voluntary expiratory phases and the absence of changes in RT during voluntary
      inspiratory phases are most likely related to disproportionally increased
      cognitive demands during the expiratory phase of voluntary breathing. The absence
      of changes in RT during voluntary inspiration is likely to be compensated by
      respiratory-motor facilitation mechanisms in this phase. Shortened RT during
      breath holding is possibly associated with increased attention.

PMID- 22643318
TI  - Laryngeal paraganglioma in an irradiated neck.
AB  - OBJECTIVE: We present the first reported case of a paraganglioma of the larynx
      occurring concurrently with squamous cell carcinoma in an irradiated neck.
      METHOD: We present a case report and a literature review of paraganglioma of the
      larynx. CASE REPORT: A 78-year-old woman was found to have a mass on the
      laryngeal surface of the epiglottis and non-functioning larynx, four months after
      radical radiotherapy for biopsy-proven squamous cell carcinoma. Repeated positron
      emission tomography computed tomography was highly suggestive of residual
      malignancy. Given these findings, and the fact that the patient was aspirating,
      she was treated with total laryngectomy, and was found to have a paraganglioma of
      the larynx. CONCLUSION: This is the first report of such a case. Its importance
      is three-fold in that it demonstrates: the coexistence of paraganglioma and
      squamous cell carcinoma; the difficulties that can be encountered in the
      diagnosis; and the use of radiotherapy in the treatment of paraganglioma.

PMID- 22643319
TI  - The impact of chronic imipramine treatment on amino acid concentrations in the
      hippocampus of mice.
AB  - The relationship between antidepressants and monoamine concentrations in the
      brain has been well investigated, but few studies have investigated the
      relationship between antidepressants and amino acid concentrations in the brain.
      The purpose of the present study was therefore to investigate the effect of the
      chronic antidepressant imipramine on amino acid and monoamine concentrations in
      the mouse brain and plasma. Chronic imipramine treatment decreased the
      concentration of 5-hydroxyindoleaceticacid/5-hydroxytryptamine in the cerebral
      cortex and increased that of norepinephrine (NE) in the hippocampus. Since these
      changes were conspicuous effects of the antidepressant, we concluded that
      imipramine acts on the central nervous system. No change in amino acid
      concentrations in plasma was induced by chronic imipramine treatment, but several
      changes were confirmed in the cerebral cortex, the hypothalamus and the
      hippocampus. Chronic imipramine treatment caused increases in L-methionine, L
      tyrosine, and L-lysine in the cerebral cortex, and an increase in L-aspartate in
      the hypothalamus. Contrary to this, the concentrations of L-aspartate, L-serine,
      L-asparagine, glycine, L-glutamine, gamma-aminobutyric acid, L-threonine, L
      arginine, L-proline, L-valine, and L-methionine in the hippocampus were decreased
      by chronic imipramine treatment. The present results demonstrate that the
      metabolism of several amino acids in the brain, but not of those in plasma, was
      altered by chronic imipramine treatment. The findings in the present study may
      help to further elucidate the relationship between amino acids and the effects
      and side effects of antidepressants.

PMID- 22643320
TI  - Automatic bladder segmentation on CBCT for multiple plan ART of bladder cancer
      using a patient-specific bladder model.
AB  - In multiple plan adaptive radiotherapy (ART) strategies of bladder cancer, a
      library of plans corresponding to different bladder volumes is created based on
      images acquired in early treatment sessions. Subsequently, the plan for the
      smallest PTV safely covering the bladder on cone-beam CT (CBCT) is selected as
      the plan of the day. The aim of this study is to develop an automatic bladder
      segmentation approach suitable for CBCT scans and test its ability to select the
      appropriate plan from the library of plans for such an ART procedure. Twenty
      three bladder cancer patients with a planning CT and on average 11.6 CBCT scans
      were included in our study. For each patient, all CBCT scans were matched to the
      planning CT on bony anatomy. Bladder contours were manually delineated for each
      planning CT (for model building) and CBCT (for model building and validation).
      The automatic segmentation method consisted of two steps. A patient-specific
      bladder deformation model was built from the training data set of each patient
      (the planning CT and the first five CBCT scans). Then, the model was applied to
      automatically segment bladders in the validation data of the same patient (the
      remaining CBCT scans). Principal component analysis (PCA) was applied to the
      training data to model patient-specific bladder deformation patterns. The number
      of PCA modes for each patient was chosen such that the bladder shapes in the
      training set could be represented by such number of PCA modes with less than 0.1
      cm mean residual error. The automatic segmentation started from the bladder shape
      of a reference CBCT, which was adjusted by changing the weight of each PCA mode.
      As a result, the segmentation contour was deformed consistently with the training
      set to fit the bladder in the validation image. A cost function was defined by
      the absolute difference between the directional gradient field of reference CBCT
      sampled on the corresponding bladder contour and the directional gradient field
      of validation CBCT sampled on the segmentation contour candidate. The cost
      function measured the goodness of fit of the segmentation on the validation image
      and was minimized using a simplex optimizer. For each validation CBCT image, the
      segmentations were done five times using a different reference CBCT. The one with
      the lowest cost function was selected as the final bladder segmentation. Volume-
      and distance-based metrics and the accuracy of plan selection were evaluated to
      quantify the performance. Two to four PCA modes were needed to represent the
      bladder shape variation with less than 0.1 cm average residual error for the
      training data of each patient. The automatically segmented bladders had a 78.5%
      mean conformity index with the manual delineations. The mean SD of the local
      residual error over all patients was 0.24 cm. The agreement of plan selection
      between automatic and manual bladder segmentations was 77.5%. PCA is an efficient
      method to describe patient-specific bladder deformation. The statistical-shape
      based segmentation approach is robust to handle the relatively poor CBCT image
      quality and allows for fast and reliable automatic segmentation of the bladder on
      CBCT for selecting the appropriate plan from a library of plans.

PMID- 22643321
TI  - Altered glucose disposition and insulin sensitivity in peri-pubertal first-degree
      relatives of women with polycystic ovary syndrome.
AB  - BACKGROUND: First-degree relatives (FDRs) of women with PCOS are at increased
      risk for impaired insulin sensitivity and diabetes mellitus. Glucose tolerant FDR
      have evidence of insulin resistance and hyperinsulinemia prior to emergence of
      frank PCOS. AIM: To study insulin dynamics parameters in the early adolescent FDR
      of women with PCOS. METHODS: This is a cross-sectional study involving 18
      adolescents whose mothers or sisters had been diagnosed with PCOS and 21 healthy,
      age-matched control adolescents without FDR. Subjects underwent anthropometric
      measurements, steroid profiling and frequently sampled Intravenous Glucose
      Tolerance Test (IVGTT), Homeostasis Model Assessment (HOMA) index, Glucose
      Disposal Index (GDI), Acute Insulin Response (AIR) and Quantitative insulin
      sensitivity check index (QUICKI) were derived from IVGTT results. RESULTS: FDRs
      showed significantly higher mean HOMA and lower GDI. There were no differences in
      mean age or BMI Z-score between the cohorts. No differences in sex steroids or
      AIR were identified between groups. CONCLUSION: Female adolescent FDR of women
      with PCOS have higher HOMA index and lower QUICKI, reflecting altered insulin
      sensitivity and lower GDI reflecting poorer beta-cell function. The presence of
      multiple risk factors for type 2 diabetes suggests that aggressive screening of
      the early adolescent FDR of women with PCOS is indicated.

PMID- 22643323
TI  - Pediatric outcomes after extracorporeal membrane oxygenation for cardiac disease
      and for cardiac arrest:  a review.
AB  - We reviewed reported survival and neurological outcomes, and predictors of these
      outcomes for pediatric cardiac extracorporeal membrane oxygenation (ECMO) and
      extracorporeal cardiopulmonary resuscitation (ECPR). We searched PubMed from 2000
      to April 2011. Cumulative survival after cardiac ECMO in children was 788/1755
      (45%); renal dysfunction, dialysis, neurologic complication, lactate, and ECMO
      duration consistently predicted this outcome, whereas single ventricle and ECPR
      did not. Neurological outcomes after cardiac ECMO were based on poorly described
      telephone questions in two studies for 47 patients with 51% significantly
      impaired and detailed follow-up testing for 42 patients in three studies with
      mental delay in 38% and mental score >85 (average or above) in 33%. Cumulative
      survival after ECPR in children was 371/762 (49%); noncardiac disease, renal
      dysfunction, neurologic complication, and pH on extracorporeal life support
      consistently predicted this outcome, whereas duration of CPR did not.
      Neurological outcomes after ECPR were based predominantly on the pediatric
      cerebral performance category (PCPC) score by chart review, with 161/181 (79%)
      having PCPC <2. No study reported detailed follow-up testing for survivors of
      ECPR. Survival outcomes of most cardiac subgroups were similar, except for
      concerning mortality in cavopulmonary connection patients. Priority areas for
      study include identification of potentially modifiable predictors of long-term
      outcomes.

PMID- 22643322
TI  - High-dose infusional gemcitabine combined with busulfan and melphalan with
      autologous stem-cell transplantation in patients with refractory lymphoid
      malignancies.
AB  - We developed a new high-dose combination of infusional gemcitabine with busulfan
      and melphalan for lymphoid tumors. Gemcitabine dose was escalated by extending
      infusions at a fixed rate of 10 mg/m(2)/min in sequential cohorts, in daily, 3
      dose or 2-dose schedules. Each gemcitabine dose immediately preceded busulfan
      (adjusted targeting area under the curve 4,000 MUM/min(-1)/day * 4 days) or
      melphalan (60 mg/m(2)/day * 2 days). We enrolled 133 patients (80 Hodgkin
      lymphoma [HL], 46 non-Hodgkin lymphoma [NHL], 7 myeloma), median 3 prior
      regimens; primary refractory disease in 63% HL/45% NHL and positron emission
      tomography positive tumors at transplantation in 50% patients. Two patients died
      from early posttransplantation infections. The major toxicity was mucositis. The
      daily and 3-dose schedules caused substantial cutaneous toxicity. In contrast,
      the 2-dose schedule was better tolerated, which allowed us to extend the
      infusions from 15 to 270 minutes. Pretransplantation values of C-reactive
      protein, B-type natriuretic peptide, ferritin, or haptoglobin did not correlate
      with toxicity. Overall response and complete response rates were 87%/62% (HL),
      100%/69% B large-cell lymphoma (B-LCL), 66%/66% (T-NHL), and 71%/57% (myeloma).
      At median follow-up of 24 months (range, 3-63 months), the event-free/overall
      survival rates were 54%/72% (HL), 60%/89% (B-LCL), 70%/70% (T-NHL), and 43%/43%
      (myeloma). In conclusion, gemcitabine/busulfan/melphalan is a feasible regimen
      with substantial activity against a range of lymphoid malignancies. This regimen
      merits further evaluation in phase II and III trials.

PMID- 22643324
TI  - Is home management of fevers a cost-effective way of reducing under-five
      mortality in Africa? The case of a rural Ghanaian District.
AB  - OBJECTIVE: To assess the cost-effectiveness of two strategies of home management
      of under-five fevers in Ghana - treatment using antimalarials only (artesunate
      amodiaquine - AAQ) and combined treatment using antimalarials and antibiotics
      (artesunate-amodiaquine plus amoxicillin - AAQ + AMX). METHODS: We assessed the
      costs and cost-effectiveness of AAQ and AAQ + AMX compared with a control
      receiving standard care. Data were collected as part of a cluster randomised
      controlled trial with a step-wedged design. Approximately, 12,000 children aged 2
      59 months in Dangme West District in southern Ghana were covered. Community
      health workers delivered the interventions. Costs were analysed from societal
      perspective, using anaemia cases averted, under-five deaths averted and
      disability-adjusted life years (DALYs) averted as effectiveness measures.
      RESULTS: Total economic costs for the interventions were US$ 204,394.72 (AAQ) and
      US$ 260,931.49 (AAQ + AMX). Recurrent costs constituted 89% and 90% of the total
      direct costs of AAQ and AAQ + AMX, respectively. Deaths averted were 79.1 (AAQ)
      and 79.9 (AAQ + AMX), with DALYs averted being 2264.79 (AAQ) and 2284.57 (AAQ +
      AMX). The results show that cost per anaemia case averted were US$ 150.18 (AAQ)
      and US$ 227.49 (AAQ + AMX) and cost per death averted was US$ 2585.58 for AAQ and
      US$ 3272.20 for AAQ + AMX. Cost per DALY averted were US$ 90.25 (AAQ) and US$
      114.21 (AAQ + AMX). CONCLUSION: Both AAQ and AAQ + AMX approaches were cost
      effective, each averting one DALY at less than the standard US$ 150 threshold
      recommended by the World Health Organisation. However, AAQ was more cost
      effective. Home management of under-five fevers in rural settings is cost
      effective in reducing under-five mortality.

PMID- 22643325
TI  - Impaired contractility and detrusor hypertrophy in cavin-1-deficient mice.
AB  - Caveolae are membrane invaginations present in a variety of cell types. Formation
      of caveolae depends on caveolins and on the more recently discovered family of
      proteins known as the cavins. Genetic ablation of caveolin-1 was previously shown
      to give rise to a number of urogenital alterations, but the effects of cavin-1
      deletion on urogenital function remain unknown. Here we characterised detrusor
      contractility and structure in cavin-1-deficient mice. Electron microscopy
      demonstrated essentially complete lack of caveolae in the knock-out detrusor, and
      immunoblotting disclosed reduced levels of cavin-3 and of all caveolin proteins.
      Bladder weight was increased in male knock-out mice, and length-tension
      relationships demonstrated a reduction in depolarisation-induced contraction.
      Contractility in response to muscarinic receptor activation was similarly
      reduced. Despite these functional changes, micturition patterns were similar in
      conscious and freely moving animals and diuresis was unchanged. Our breeding
      additionally disclosed that the number of knock-out mice generated in
      heterozygous crosses was lower than expected, suggesting embryonic/perinatal
      lethality. In conclusion, this is the first study to show that cavin-1 is
      critical for detrusor caveolae and for the overall contractility and structure of
      the urinary bladder.

PMID- 22643327
TI  - When life gives you lemons, make lemonade!

PMID- 22643326
TI  - Diverse effects of 5-HT2C receptor blocking agents on c-Fos expression in the rat
      basal ganglia.
AB  - Serotonin(2C) receptors (5-HT(2)C) exert continuous control on the activity of
      specific populations of neurons in the basal ganglia. While antagonists block the
      effect of endogenous 5-HT at 5-HT(2C) receptors, the actions of inverse agonists
      may also involve interruption of activity at constitutively active populations of
      5-HT(2C) receptors. We have evaluated the regional impact of these controls by
      studying, in rats, the expression of the product of the proto-oncogene c-Fos in
      rat basal ganglia after peripheral doses of the 5-HT(2C) antagonist SB 243213 (5
      methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6
      trifluoromethylindoline) and the 5-HT(2B/2C) inverse agonists SB 206553 (5-methyl
      1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole.hydrochloride) and
      S32006 (N-pyridin-3-yl-1,2-dihydro-3H-benzo[e]indole-3-carboxamide). The results
      show that 1 and 10mg/kg SB 243213 enhanced equally c-Fos expression in the
      subthalamic nucleus (STN) and dose-dependently in the striatum and nucleus
      accumbens core (NAcc). SB 206553 (1-10mg/kg), at 10mg/kg only, enhanced c-Fos
      expression in STN, striatum (except the dorsomedial part), NAcc, entopeduncular
      nucleus, substantia nigra pars reticulata (SNr) and compacta (SNc) and ventral
      tegmental area. S32006 induced a similar increase in c-Fos expression in the
      medial parts of the striatum and NAcc at doses of 1-10mg/kg while it dose
      dependently enhanced c-Fos expression in medial parts of the STN and SNr. None of
      these drugs induced c-Fos expression in the globus pallidus. The distinct pattern
      of c-Fos expression elicited by the 5-HT(2C) antagonist and inverse agonists
      suggests the existence of cellular and functional heterogeneity in the response
      of the basal ganglia to drugs inhibiting 5-HT(2C) receptors.

PMID- 22643328
TI  - Facial nerve palsy as a complication of ear syringing.
AB  - INTRODUCTION: Syringing of the ear is one of the most common procedures performed
      for cleaning cerumen from the external auditory canal. Common complications
      following syringing are pain, external auditory canal trauma and otitis externa.
      Hearing and vestibular loss have also been reported as complications. However, we
      are unaware of any report of facial nerve palsy as a complication of ear
      syringing. Such a case is reported. CASE PRESENTATION: We describe a case of
      facial nerve palsy as a complication of syringing, which demonstrates the
      dramatic presentation of this condition and emphasises the need for great care
      while syringing the ears. CONCLUSION: It is important to be aware of this unusual
      complication with its distinctive presentation. Surgical intervention should be
      undertaken at the earliest opportunity, for favourable results. A risk-minimising
      strategy for ear syringing is recommended.

PMID- 22643329
TI  - Assessing hopping developmental level in childhood using wearable inertial sensor
      devices.
AB  - Assessing movement skills is a fundamental issue in motor development. Current
      process-oriented assessments, such as developmental sequences, are based on
      subjective judgments; if paired with quantitative assessments, a better
      understanding of movement performance and developmental change could be obtained.
      Our purpose was to examine the use of inertial sensors to evaluate developmental
      differences in hopping over distance. Forty children executed the task wearing
      the inertial sensor and relevant time durations and 3D accelerations were
      obtained. Subjects were also categorized in different developmental levels
      according to the hopping developmental sequence. Results indicated that some time
      and kinematic parameters changed with some developmental levels, possibly as a
      function of anthropometry and previous motor experience. We concluded that, since
      inertial sensors were suitable in describing hopping performance and sensitive to
      developmental changes, this technology is promising as an in-field and user
      independent motor development assessment tool.

PMID- 22643330
TI  - Reconstitution of 6-sulfo LacNAc dendritic cells after allogeneic stem-cell
      transplantation.
AB  - BACKGROUND: Infections and acute graft-versus-host disease (GvHD) represent major
      complications of allogeneic stem-cell transplantation (SCT). Dendritic cells
      (DCs) display an extraordinary capacity to induce innate and adaptive immune
      responses. Therefore, they play a crucial role in the elimination of pathogens
      and in the pathogenesis of acute GvHD. 6-Sulfo LacNAc DCs (slanDCs) are a major
      subpopulation of human blood DCs with a high proinflammatory capacity. We
      investigated for the first time the reconstitution of slanDCs in the blood of
      patients after SCT and the modulation of their frequency by bacterial infection,
      cytomegalovirus (CMV) reactivation, and acute GvHD. METHODS: The frequency of
      slanDCs, CD1c myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) in the peripheral
      blood was quantified by flow cytometry in 80 patients after SCT. To assess
      individual DC subsets, we used pregating of the HLADRLin subset and antibodies
      against slanDCs, blood DC antigen 1 (CD1c mDCs), and blood DC antigen 2 (pDCs).
      RESULTS: SlanDCs showed the slowest reconstitution in the first month after SCT
      compared with CD1c mDCs and pDCs. Interestingly, in the second and third months
      after SCT, their percentage steadily increased, and slanDCs were the most
      abundant DC subset. In addition, we observed a markedly reduced frequency of
      slanDCs in the blood of patients with bacterial infection, CMV reactivation, or
      severe acute GvHD. Furthermore, slanDCs showed the most prominent reduction after
      steroid treatment of acute GvHD. CONCLUSIONS: These results indicate that SCT
      associated complications such as bacterial infection, CMV reactivation, and acute
      GvHD can significantly modulate the frequency of slanDCs.

PMID- 22643331
TI  - Inhibitory effect of tacrolimus on p38 mitogen-activated protein kinase signaling
      in kidney transplant recipients measured by whole-blood phosphospecific flow
      cytometry.
AB  - BACKGROUND: Tacrolimus (TAC), the cornerstone of immunosuppressive therapy after
      solid organ transplantation, inhibits calcineurin activation. Despite
      pharmacokinetic monitoring, patients frequently experience toxicity or lack of
      efficacy, which could be prevented by pharmacodynamic monitoring. In Jurkat T
      cell lines, it has been shown that TAC, in addition to calcineurin, inhibits the
      p38 mitogen-activated protein kinase (MAPK) pathway, which is important in T-cell
      activation and is therefore a potential drug-specific biomarker. We studied
      whether TAC inhibits p38 MAPK signaling in primary human T cells and ex vivo in
      healthy volunteers and kidney transplant recipients. METHODS: Phorbol-12
      myristate-13-acetate/ionomycin-induced MAPK signaling was measured by whole-blood
      phosphospecific flow cytometry. RESULTS: In vitro, 10-ng/mL TAC inhibited p38
      MAPK phosphorylation by a mean of 27% in CD3, 26% in CD4, and 34% in CD8 T cells
      (P<0.01 compared with baseline). In healthy adults (n=4), 2 hr after a single
      oral dose of 10-mg TAC, the p38 MAPK activation was inhibited by 35% in CD3, CD4,
      and CD8 T cells (P<0.05 compared with baseline). In kidney transplant recipients
      (n=24), TAC predose concentrations (range, 3.2-10.5 ng/mL) were inversely
      correlated with p38 MAPK activation in CD3, CD4, and CD8 T cells (r=0.51, 0.34,
      and 0.37, respectively; P<0.01). CONCLUSIONS: TAC inhibits activation of the MAPK
      pathway in a dose-dependent manner in kidney transplant patients and may be a
      potential marker for immune monitoring.

PMID- 22643333
TI  - One-pot synthesis of highly crystalline mesoporous TiO2 nanoparticle assemblies
      with enhanced photocatalytic activity.
AB  - We report an unprecedented formation of mesoporous titania via a surfactant
      assisted aggregating assembly of TiO(2) nanoparticles. These mesostructures
      possess a highly crystalline anatase phase, large and accessible pore surface
      area, and exhibit superior photocatalytic performance.

PMID- 22643332
TI  - Dendritic cells conditioned with NK026680 prolong cardiac allograft survival in
      mice.
AB  - BACKGROUND: Pharmacologically modulated dendritic cells (DCs) can potentially
      regulate alloimmune responses. We examined the characteristics of
      immunoregulatory DCs induced by a novel triazolopyrimidine derivative, NK026680,
      which has been previously shown to inhibit DC maturation. METHODS: DCs were
      generated from bone marrow progenitor cells from C57BL/6 (B6, H-2 haplotype) mice
      with granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4. DCs
      were cultured with allogeneic BALB/c (H-2) splenocyte lysates with or without
      NK026680. DC functions were examined in vitro after stimulation of tumor necrosis
      factor alpha and in vivo by the intravenous injection of C3He/J (C3H, H-2) DCs
      cultured with B6 cell lysates and NK026680 into C3H mice. Seven days later, DC
      treated mice received B6 heart allografts, and graft survival and alloimmune
      responses were assessed. RESULTS: In NK026680-treated DCs (NK-DCs), significant
      inhibition of the up-regulation of surface activation markers (CD40, CD80, CD86,
      and major histocompatibility complex class II) and IL-12 p40 production was
      observed after stimulation of tumor necrosis factor alpha compared with that of
      control DCs. Furthermore, NK-DCs suppressed alloreactive T-cell proliferation.
      The modulation of NK-DCs was likely associated with the inhibition of
      phosphorylation of p38 mitogen-activated protein kinase and the up-regulation of
      indolamine 2,3-dioxygenase expression. Compared with both noninjected and control
      DC-injected mice, mice that received a single in vivo infusion of NK-DCs showed
      significant increases in splenocyte IL-10 production and the splenic CD4 IL-10 T
      cell population 7 days after injection, a significantly increased splenic
      CD4CD25FoxP3 T-cell population 14 days after injection, and markedly prolonged
      cardiac allograft survival. CONCLUSIONS: Ex vivo NK026680 conditioning allows DCs
      to acquire immunoregulatory properties that suppress alloimmune responses and
      prolong cardiac allograft survival.

PMID- 22643334
TI  - Influence of respirometry methods on intraspecific variation in standard
      metabolic rates in newts.
AB  - Standard metabolic rate (SMR) is both a highly informative and variable trait.
      Variation in SMR stems not only from diverse intrinsic and extrinsic factors, but
      also from the use of diverse methods for metabolic measurements. We measured
      CO(2) production (VCO(2)) and oxygen consumption rates (VO(2)) using two flow
      through respirometry modes, continuous and intermittent (stop-flow), to evaluate
      their potential contribution to SMR variation in Alpine newts, Ichthyosaura
      alpestris. Both respirometry modes yielded similar and repeatable VCO(2) values.
      Although VO(2) was highly repeatable, continuous respirometry produced lower
      VO(2) than the intermittent method. During intermittent measurements, the total
      number of activity bouts was higher than during continuous respirometry trials.
      Statistical correction for disparate activity levels minimized variation in
      oxygen consumption between respirometry modes. We conclude that use of either
      method of flow-through respirometry, if properly applied, introduced less noise
      to SMR estimates than a variation in activity levels.

PMID- 22643335
TI  - Fatty acid mobilization in voles--model species for rapid fasting response and
      fatty liver.
AB  - Factors regulating fatty acid (FA) composition of small herbivores are poorly
      known. Because of the fast response to food deprivation, the tissue FA profiles
      of voles could be rapidly modified. The selectivity of incorporating dietary FA
      into tissue total lipids and mobilizing tissue FA was examined in two Microtus
      vole species either fed or fasted for 12-18 h. The FA composition of the tissues
      reflected the dietary lipids, but FA were selectively incorporated depending on
      their structure. The FA profiles of white and brown adipose tissues were
      different and contained more saturated and monounsaturated FA and less
      polyunsaturated FA (PUFA) than the diet. The essential PUFA precursors with
      smaller tissue percentages were likely converted into longer-chain derivatives
      for structural lipids. The FA composition of the vole tissues was selectively
      modified by food deprivation. The preferences for retention or loss were tissue
      specific and related to the FA structure. Livers displayed steatosis with
      characteristic accumulation of triacylglycerols, while FA prevalent in membrane
      phospholipids decreased in proportion. Hepatic FA could be partly derived from
      lipids hydrolyzed in fat depots. The FA profiles of the vole tissues reflect the
      dietary lipids and are rapidly and selectively modified by food deprivation.

PMID- 22643336
TI  - Effects of long-term cortisol treatments on gonadal development, sex steroids
      levels and ovarian cortisol content in cultured great sturgeon Huso huso.
AB  - The objective of this study was to examine the effect of cortisol implantations
      on gonadal development, sex steroid levels, and ovarian cortisol content in
      cultured great sturgeon Huso huso. Three groups of 5 fish for each treatment were
      considered. The experimental groups included: control (capsules containing cocoa
      butter alone), low cortisol (C(5); 5mg cortisol/kg body mass+cocoa butter) and,
      high cortisol (C(50); 50mg cortisol/kg body mass+cocoa butter). The capsules
      containing hormones and cocoa butter were intraperitoneally implanted into 3-year
      old female fish at pre-vitellogenic stage (mean initial body mass 6809.7 +/- 73
      g) every 6 weeks over a 6-month period from January to June. The serum levels of
      cortisol, glucose, cholesterol and sex steroids (testosterone and 17beta
      estradiol) were determined at the initial time and three weeks after each
      implantation. Oocyte histological characteristics (the diameter and area of the
      oocyte, the diameter and area of the nucleus and the ratio of the nucleus area to
      the oocyte area) were measured at the end of the experiment and compared to those
      at the initial time. Ovarian cortisol content was measured at the end of the
      experiment. The results showed that serum cortisol levels varied in a dose
      independent manner, so that the highest cortisol concentrations were observed in
      C(5)-treated fish throughout the experiment. Serum glucose levels were
      significantly higher in cortisol-treated groups than those in the control group.
      The high dose of cortisol elicited a significant constant increase in serum
      cholesterol concentrations. Fish implanted with the high cortisol dose showed
      significant declines in serum testosterone and 17beta-estradiol concentrations
      throughout the experiment. No significant differences were found in oocyte
      histological characteristics among experimental groups. The cortisol implants
      elicited a dose-dependent increase in ovarian cortisol content. At the end of
      trial, body-growth indices were the lowest in C(50)-implanted fish, while the low
      cortisol dose had no effect on growth relative to the controls. These results
      indicated that chronic stress induced by cortisol implantation in great sturgeon
      suppressed gonadal steroidogenesis and somatic growth but had no effect on
      ovarian growth and development.

PMID- 22643337
TI  - Daily patterns of mRNA expression of two core circadian regulatory proteins,
      Clock2 and Per1, and two appetite-regulating peptides, OX and NPY, in goldfish
      (Carassius auratus).
AB  - The aim of this study was to examine the daily hypothalamic mRNA expression
      profiles for two core circadian regulatory proteins, CLOCK2 and PER1, and for two
      neuropeptides that regulate wakefulness and food intake, OX and NPY, in goldfish.
      The profiles were determined for fish at different nutritional states (i.e. fed
      or unfed on sampling day) and held at different photoperiods (i.e. 16L:8D
      photoperiod vs. constant light LL). Our results show that under a 16L:8D
      photoperiod, both fed and unfed goldfish exhibit clear antiphasic daily rhythms
      of hypothalamic Clock2 and Per1 mRNA expression levels, whereas under LL, daily
      Clock2 rhythms are seen in both fed and unfed fish while significant rhythms of
      Per1 mRNA expression only persist in unfed fish. In fish held under 16L:8D, but
      not under LL, there was significantly higher Per1 expression in fed fish at
      feeding time than in unfed fish. Daily variations in hypothalamic OX mRNA
      expression levels with peaks observed prior to both feeding time and the onset of
      darkness, were displayed under a 16L:8D photoperiod, whereas exposure to LL
      resulted in lower expression levels with no significant daily variations. Fish
      held under LL, but not under 16L:8D, showed significant daily variations in NPY
      mRNA expression with a peak prior to feeding time. Taken together, our results
      suggest that the mRNA expression of both appetite-regulating and circadian
      proteins display daily variations and that these patterns can be affected by
      external cues such as feeding and photoperiod.

PMID- 22643338
TI  - Gene transcripts encoding hypoxia-inducible factor (HIF) exhibit tissue- and
      muscle fiber type-dependent responses to hypoxia and hypercapnic hypoxia in the
      Atlantic blue crab, Callinectes sapidus.
AB  - Hypoxia inducible factor (HIF) is a transcription factor that under low
      environmental oxygen regulates the expression of suites of genes involved in
      metabolism, angiogenesis, erythropoiesis, immune function, and growth. Here, we
      isolated and sequenced partial cDNAs encoding hif-alpha and arnt/hif-beta from
      the Atlantic blue crab, Callinectes sapidus, an estuarine species that frequently
      encounters concurrent hypoxia (low O(2)) and hypercapnia (elevated CO(2)). We
      then examined the effects of acute exposure (1h) to hypoxia (H) and hypercapnic
      hypoxia (HH) on relative transcript abundance for hif-alpha and arnt/hif-beta in
      different tissues (glycolytic muscle, oxidative muscle, hepatopancreas, gill, and
      gonads) using quantitative real-time RT-PCR. Our results indicate that hif-alpha
      and arnt/hif-beta mRNAs were constitutively present under well-aerated normoxia
      (N) conditions in all tissues examined. Further, H and HH exposure resulted in
      both tissue-specific and muscle fiber type-specific effects on relative hif-alpha
      transcript abundance. In the gill and glycolytic muscle, relative hif-alpha mRNA
      levels were significantly lower under H and HH, compared to N, while no change
      (or a slight increase) was detected in oxidative muscle, hepatopancreas and
      gonadal tissues. H and HH did not affect relative transcript abundance for
      arnt/hif-beta in any tissue or muscle fiber type. Thus, in crustaceans the HIF
      response to H and HH appears to involve changes in hif transcript abundance, with
      variation in hif-alpha and arnt/hif-beta transcriptional dynamics occurring in
      both a tissue- and muscle fiber type-dependent manner.

PMID- 22643339
TI  - Effects of perinatal undernutrition on the development of neurons in the rat
      insular cortex.
AB  - The insular cortex (IC) of the rat is a major area for the convergence and
      integration of olfactory, gustatory, and visual information, and at present it is
      unclear if perinatal undernutrition interferes with the structure and function of
      the IC neurons. Golgi-Cox-stained cells  of the IC were studied in control and
      undernourished Wistar rats at 12, 20, and 30 days of age. Pregnant dams were
      undernourished by the reduction of a balanced diet during a part of the
      gestational period (G6-G18). After parturition (P1-P23) pups remained for 12
      hours with a  normal and 12 hours with a nipple-ligated dam. Undernutrition
      significantly reduced the number, and the arborization of the dendritic arbors,
      and the perimeter, and cross-sectional area of perikarya. The IC neuronal
      morphology appearances suggest a possible mechanism for the impairment in 
      information processing of complex phenomena such as taste sensation and hedonic
      response.

PMID- 22643340
TI  - Investigation of the sag in linac secondary collimator and MLC carriage during
      arc deliveries.
AB  - In modern radiotherapy, it is vitally important to monitor the performance of all
      linac components including the collimation system. In this study, a simple
      measurement method and accurate algorithm are introduced for investigation of the
      secondary and tertiary collimator sag during radiotherapy arc treatments. The
      method is based on cine EPID images of a ball bearing marker fixed to the gantry
      head and determines the jaw and MLC sag in all directions relative to the
      reference at zero gantry angle. Analysis was performed using different field
      sizes and collimator angles, different linacs and different gantry rotation
      directions. The accuracy of the method was tested and was less than 0.02 mm. The
      repeatability and reproducibility of the method was 0.005 and 0.09 mm,
      respectively. The setup is easy and quick and the algorithm is fast and fully
      automatic with sub-pixel accuracy. This method is suitable to be included in the
      routine quality assurance of linacs to monitor the collimator system performance.

PMID- 22643341
TI  - Serum osmolality and effects of water deprivation in captive Asian elephants
      (Elephas maximus).
AB  - Serum from 21 healthy, captive Asian elephants (Elephas maximus) was evaluated by
      measured and calculated osmolality. Serum osmolality results for this population
      of Asian elephants had a median of 261 mOsm/kg and an interquartile interval of
      258-269 mOsm/kg when measured by freezing point osmometry and a median of 264
      mOsm/kg and an interquartile interval of 257-269 mOsm/kg when measured by vapor
      pressure osmometry. These values are significantly lower than values reported in
      other mammalian species and have important diagnostic and therapeutic
      implications. Calculated osmolality produced unreliable results and needs further
      study to determine an appropriate formula and its clinical application in this
      species. A 16-hr water deprivation test in 16 Asian elephants induced a small,
      subclinical, but statistically significant increase in measured serum osmolality.
      Serum osmolality, blood urea nitrogen, and total protein by refractometer were
      sensitive indicators of hydration status. Serum osmolality measurement by
      freezing point or vapor pressure osmometry is a useful adjunct to routine
      clinical tests in the diagnostic evaluation of elephants.

PMID- 22643343
TI  - Eosinophilic granulocytic sarcoma in a pig.
AB  - A case of granulocytic sarcoma originating from an eosinophilic lineage is
      described in a 5-year-old, mixed-breed, female pig. The pig had been originally
      sent to slaughter in a good plane of nutrition and without displaying clinical
      disease. At gross examination, green masses were observed in several bones,
      especially vertebrae, sternum, pelvis, and long bones such as femur and humerus.
      Similar masses were seen in skeletal muscles, lymph nodes, and kidneys. Cytology
      revealed large numbers of round cells with round nuclei and scant cytoplasm
      (myelocytes); some of these cells had a fine eosinophilic granularity to their
      cytoplasm (eosinophil myelocytes). Histologically, the neoplastic cells formed
      sheets that completely obliterated the normal architecture of subperiosteal bone
      marrow. The cytoplasm of the neoplastic cells stained strongly by Sirius red
      stain of eosinophil and was positively marked by immunohistochemistry using an
      anti-myeloperoxidase antibody. The association of gross examination, cytology,
      histology, histochemistry, and immunohistochemistry findings is consistent with a
      diagnosis of eosinophilic granulocytic sarcoma.

PMID- 22643342
TI  - Assessment of ruminal hydrogen sulfide or urine thiosulfate as diagnostic tools
      for sulfur induced polioencephalomalacia in cattle.
AB  - To determine if ruminal hydrogen sulfide, urine thiosulfate, or blood
      sulfhemoglobin could be used as diagnostic indicators for sulfur-induced
      polioencephalomalacia, 16 steers (8 cannulated, 368 +/- 12 kg; 8 unmodified, 388
      +/- 10 kg; mean +/- standard error) were fed 1 of 2 dietary treatments. Diets
      consisted of a low sulfate (0.24% S; control) wheat midd-based pellet or the
      control pellet with sodium sulfate added to achieve a high-sulfate (0.68% S)
      pellet. As designed, intake did not differ (P = 0.80) between treatments. At 8 hr
      postfeeding, ruminal hydrogen sulfide was not affected by cannulation (P = 0.35)
      but was greater (P < 0.01) in high S (6,005 +/- 475 mg/l) than control (1,639 +/-
      472 mg/l) steers. Time of day of sampling affected (P = 0.01) ruminal hydrogen
      sulfide, with peak concentrations occurring 4-12 hr after feeding. Urine was
      collected prefeeding (AM) and 7-9 hr postfeeding (PM). Urine thiosulfate
      concentrations of high S steers sampled in the PM were greater (P > 0.01) than in
      the AM. However, there was no difference due to time of sampling for control. In
      both the AM and PM, urine thiosulfate concentrations of high S were greater (P >
      0.01) than control. Although hydrogen sulfide and thiosulfate were elevated by
      increased dietary S intake, a concentration at which polioencephalomalacia is
      likely to occur could not be determined. Sampling urine for thiosulfate or rumen
      gas for hydrogen sulfide of nonsymptomatic pen mates 4-8 hr after feeding may be
      useful to assess sulfur exposure and differentiate between causes of
      polioencephalomalacia.

PMID- 22643344
TI  - Perforating abomasal ulcer caused by yolk sac tumor in a Holstein calf.
AB  - A 2-month-old male Holstein calf showed clinical signs of abdominal bloating,
      melena, and pain and was suspected of having a perforating abomasal ulcer.
      Necropsy revealed a large mass located preferentially around the abomasum and a
      large perforating abomasal ulcer on the pyloric antrum. Milky white masses of
      various sizes were also found in the abdominal cavity that consisted of
      agglutinated nodules ranging in size from a pinhead to a golf ball and were
      distributed on the surfaces of the liver, reticulum, omasum, abomasum, and
      diaphragm. Microscopic examination revealed that the masses were composed
      primarily of hyaline matrices, epithelioid tumor cells, and large atypical cells
      with hyaline droplets and/or vacuoles. Stromal hyaline matrices and hyaline
      droplets of the large tumor cells stained positive with periodic acid-Schiff
      stain. Tumor cells showed a positive reaction to anti-human alpha-fetoprotein,
      which is a marker of yolk sac tumors. These findings strongly suggested that the
      masses found in the abdominal cavity were yolk sac tumor, a rare germ cell tumor
      in cattle.

PMID- 22643345
TI  - Regadenoson:  review of its established role in myocardial perfusion imaging and
      emerging applications.
AB  - Myocardial perfusion imaging is a well-established noninvasive modality for the
      diagnosis and prognosis of coronary artery disease. The pharmacologic stress
      agents adenosine and dipyridamole are widely used in imaging studies, but cause
      undesirable side effects, like atrioventricular block and bronchospasm, due to
      their nonselective adenosine receptor activation. Furthermore, the mode of
      administration of these agents as a bolus infusion is less preferred.
      Regadenoson, an A2A adenosine receptor selective pharmacologic stress agent was
      approved in 2008 and is widely used instead of adenosine and dipyridamole. This
      article reviews regadenosons structure, mechanism of action, advantages over
      adenosine and dipyridamole, and its role in various patient populations
      undergoing stress perfusion imaging. Emerging applications where regadenoson
      could be of potential use are also explored.

PMID- 22643346
TI  - The use of left ventricular assist devices in the treatment of class IV heart
      failure patients: what the non-heart failure specialist needs to know.
AB  - The New York Heart Association class IV heart failure patient represents a very
      sick patient population with a poor 6-month survival rate. With appropriate
      selection and timing, left ventricular assist devices can provide improved
      outcomes while these patients are supported for bridge to heart transplant or
      destination therapy. As the number of heart failure patients supported by left
      ventricular assist devices increases, physicians will need to be familiar with
      postoperative chronic issues (such as right ventricular failure, infection,
      hypertension, atrial fibrillation, bleeding, and thromboembolic events) that can
      affect the function of these devices.

PMID- 22643347
TI  - A hot topic: temperature sensitive sodium channelopathies.
AB  - Perturbations to body temperature affect almost all cellular processes and,
      within certain limits, results in minimal effects on overall physiology. Genetic
      mutations to ion channels, or channelopathies, can shift the fine homeostatic
      balance resulting in a decreased threshold to temperature induced disturbances.
      This review summarizes the functional consequences of currently identified
      voltage-gated sodium (NaV) channelopathies that lead to disorders with a
      temperature sensitive phenotype. A comprehensive knowledge of the relationships
      between genotype and environment is not only important for understanding the
      etiology of disease, but also for developing safe and effective treatment
      paradigms.

PMID- 22643348
TI  - Measurement of spleen stiffness to evaluate portal hypertension and the presence
      of esophageal varices in patients with HCV-related cirrhosis.
AB  - BACKGROUND & AIMS: The hepatic vein pressure gradient (HVPG) is the standard used
      to determine the degree of portal hypertension (PH) and an important prognostic
      factor for patients with cirrhosis; HVPG values correlate with the presence of
      esophageal varices (EV). However, HVPG can only be accurately determined at
      specialized centers; noninvasive methods are needed to predict HVPG values and
      the presence of EV. We compared the diagnostic performance of spleen stiffness
      (SS) measurement by transient elastography with that of liver stiffness (LS) and
      of other recently proposed noninvasive tests. METHODS: We measured SS and LS in
      100 consecutive patients with hepatitis C virus-induced cirrhosis. Patients were
      also assessed by FibroScan, HVPG, esophagogastroduodenoscopy, and liver biopsy.
      We also analyzed LS-spleen diameter to platelet ratio score and platelet count to
      spleen diameter. RESULTS: SS and LS were more accurate than other noninvasive
      parameters in identifying patients with EV and different degrees of PH. A linear
      model that included SS and LS accurately predicted HVPG values (R(2) = 0.85). The
      results were internally validated using bootstrap analysis. CONCLUSIONS:
      Measurement of SS can be used for noninvasive assessment and monitoring of PH and
      to detect EV in patients with hepatitis C virus-induced cirrhosis.

PMID- 22643350
TI  - Efficacy of entecavir with or without tenofovir disoproxil fumarate for
      nucleos(t)ide-naive patients with chronic hepatitis B.
AB  - BACKGROUND & AIMS: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are
      potent antiviral agents that might have additive or synergistic antiviral
      activity in treatment of patients with chronic hepatitis B (CHB). We compared the
      efficacy and safety of ETV monotherapy with those of a combination of ETV and
      TDF. METHODS: We performed a randomized, open-label, multicenter, superiority
      study of 379 nucleos(t)ide-naive patients with hepatitis B e antigen (HBeAg)
      positive (n = 264) or HBeAg-negative (n = 115) CHB. Subjects were given ETV 0.5
      mg (n = 182) or a combination of ETV 0.5 mg and TDF 300 mg (n = 197) for 100
      weeks. RESULTS: At week 96, comparable proportions of patients in each study arm
      achieved the primary end point of a level of hepatitis B virus (HBV) DNA <50
      IU/mL (83.2% vs 76.4%; P = .088). Among HBeAg-positive patients, a greater
      proportion given combination therapy achieved levels of HBV DNA <50 IU/mL than
      those given ETV alone (80.4% vs 69.8%; P = .046). However, this difference was
      observed only in patients with baseline levels of HBV DNA >= 10(8) IU/mL (79% vs
      62%) and not in those with baseline levels of HBV DNA <10(8) IU/mL (83% in both
      arms). Rates of HBeAg loss and HBeAg seroconversion were comparable between
      groups, whereas the rate of alanine aminotransferase normalization was greater in
      the ETV monotherapy group. No HBV variants associated with ETV or TDF resistance
      were detected. Safety profiles were consistent with previous reports of ETV or
      TDF monotherapy. CONCLUSIONS: The antiviral efficacy of ETV monotherapy is
      comparable to that of ETV plus TDF in a mixed population of nucleos(t)ide-naive
      patients with CHB (70% HBeAg positive). The combination therapy could provide an
      incremental benefit to HBeAg-positive patients with baseline levels of HBV DNA >=
      10(8) IU/mL.

PMID- 22643349
TI  - Abnormal initiation and conduction of slow-wave activity in gastroparesis,
      defined by high-resolution electrical mapping.
AB  - BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) generate slow waves.
      Disrupted ICC networks and gastric dysrhythmias are each associated with
      gastroparesis. However, there are no data on the initiation and propagation of
      slow waves in gastroparesis because research tools have lacked spatial
      resolution. We applied high-resolution electrical mapping to quantify and
      classify gastroparesis slow-wave abnormalities in spatiotemporal detail. METHODS:
      Serosal high-resolution mapping was performed using flexible arrays (256
      electrodes; 36 cm(2)) at stimulator implantation in 12 patients with diabetic or
      idiopathic gastroparesis. Data were analyzed by isochronal mapping, velocity and
      amplitude field mapping, and propagation animation. ICC numbers were determined
      from gastric biopsy specimens. RESULTS: Mean ICC counts were reduced in patients
      with gastroparesis (2.3 vs 5.4 bodies/field; P < .001). Slow-wave abnormalities
      were detected by high-resolution mapping in 11 of 12 patients. Several new
      patterns were observed and classified as abnormal initiation (10/12; stable
      ectopic pacemakers or diffuse focal events; median, 3.3 cycles/min; range, 2.1
      5.7 cycles/min) or abnormal conduction (7/10; reduced velocities or conduction
      blocks; median, 2.9 cycles/min; range, 2.1-3.6 cycles/min). Circumferential
      conduction emerged during aberrant initiation or incomplete block and was
      associated with velocity elevation (7.3 vs 2.9 mm s(-1); P = .002) and increased
      amplitudes beyond a low base value (415 vs 170 MUV; P = .002). CONCLUSIONS: High
      resolution mapping revealed new categories of abnormal human slow-wave activity.
      Abnormalities of slow-wave initiation and conduction occur in gastroparesis,
      often at normal frequency, which could be missed by tests that lack spatial
      resolution. Irregular initiation, aberrant conduction, and low amplitude activity
      could contribute to the pathogenesis of gastroparesis.

PMID- 22643352
TI  - Observation of 1,3-diketones formation in the reaction of bulky acyl chlorides
      with methyllithium.
AB  - The formation of 1,3-diketones was observed in the reactions of bulky acyl
      chlorides with methyllithium. The reaction products depend on the steric
      hindrance around the carbonyl group of the acyl chloride and the electronic
      effect of the group(s) linked to the carbonyl. When the steric hindrance around
      the carbonyl group of the acyl chloride is big enough, the 1,3-diketone is the
      only product. In the case of the moderate hindrance around the carbonyl group of
      the acyl chloride, a moderate yield of 1,3-diketone is obtained and some tertiary
      alcohol is generated. When there is no steric hindrance around the carbonyl group
      of the acyl chloride, the tertiary alcohol is the only product. When the steric
      hindrance around the carbonyl group is moderate and an electron-donating group is
      connected to the carbonyl of the acyl chloride, all three products--ketone, 1,3
      diketone and tertiary alcohol--can be isolated from the reaction mixture after
      long reaction times.

PMID- 22643353
TI  - Two new diterpenoids from the buds of Wikstroemia chamaedaphne.
AB  - Two new diterpenoids, wikstroelide Q (1) and prostratin Q (5), together with
      three known diterpenoids, pimelea factors P2 (2), P3 (3), and prostratin (4), and
      five known lignans, (+)-epipioresinol (6), (+)-isolariciresinol (7), (-)
      lariciresinol (8), (+)-epi-sesaminone (9), and prestegane B (10), were isolated
      from the buds of Wikstroemia chamaedaphne Meissn. Their structures were
      elucidated by a combination of spectroscopic analyses. Compounds 1-10 were
      evaluated for their cytotoxicities against HL-60, SMMC-7721, A549, MCF-7, SW480,
      and BEAS-2B cell lines in vitro.

PMID- 22643351
TI  - A role for the epidermal growth factor receptor signaling in development of
      intestinal serrated polyps in mice and humans.
AB  - BACKGROUND & AIMS: Epithelial cancers can be initiated by activating mutations in
      components of the mitogen-activated protein kinase signaling pathway such as v
      raf murine sarcoma viral oncogene homolog B1 (BRAF), v-Ki-ras2 Kirsten rat
      sarcoma viral oncogene homolog (KRAS), or epidermal growth factor receptor
      (EGFR). Human intestinal serrated polyps are a heterogeneous group of benign
      lesions, but some progress to colorectal cancer. Tumors that arise from these
      polyps frequently contain activating mutations in BRAF or KRAS, but little is
      known about the role of EGFR activation in their development. METHODS: Polyp
      samples were obtained from adults during screening colonoscopies at Mount Sinai
      Hospital in New York. We measured levels of EGFR protein and phosphorylation in
      human serrated polyps by immunohistochemical and immunoblot analyses. We
      generated transgenic mice that express the ligand for EGFR, Heparin-binding EGF
      like growth factor (HB-EGF), in the intestine. RESULTS: EGFR and the
      extracellular-regulated kinases (ERK)1/2 were phosphorylated in serrated areas of
      human hyperplastic polyps (HPPs), sessile serrated adenomas, and traditional
      serrated adenomas. EGFR and ERK1/2 were phosphorylated in the absence of KRAS or
      BRAF activating mutations in a subset of HPP. Transgenic expression of the EGFR
      ligand HB-EGF in the intestines of mice promoted development of small cecal
      serrated polyps. Mice that expressed a combination of HB-EGF and US28 (a
      constitutively active, G-protein-coupled receptor that increases processing of HB
      EGF from the membrane) rapidly developed large cecal serrated polyps. These
      polyps were similar to HPPs and had increased phosphorylation of EGFR and ERK1/2
      within the serrated epithelium. Administration of pharmacologic inhibitors of
      EGFR or MAPK to these transgenic mice significantly reduced polyp development.
      CONCLUSIONS: Activation of EGFR signaling in the intestine of mice promotes
      development of serrated polyps. EGFR signaling also is activated in human HPPs,
      sessile serrated adenomas, and traditional serrated adenomas.

PMID- 22643354
TI  - Synthesis, spectroscopy, thermal analysis, magnetic properties and biological
      activity studies of Cu(II) and Co(II) complexes with Schiff base dye ligands.
AB  - Three azo group-containing Schiff base ligands, namely 1-{3-[(3
      hydroxypropylimino) methyl]-4-hydroxyphenylazo}-4-nitrobenzene (2a), 1-{3-[(3
      hydroxypropylimino) methyl]-4-hydroxyphenylazo}-2-chloro-4-nitrobenzene (2b) and
      1-{3-[(3-hydroxypropylimino) methyl]-4-hydroxyphenylazo}-4-chloro-3-nitrobenzene
      (2c) were prepared. The ligands were characterized by elemental analysis, FTIR
      spectroscopy, UV-Vis spectroscopy, 13C- and 1H-NMR spectroscopy and
      thermogravimetric analysis. Next the corresponding copper(II) and cobalt(II)
      metal complexes were synthesized and characterized by the physicochemical and
      spectroscopic methods of elemental analysis, FTIR spectroscopy, UV-Vis
      spectroscopy, magnetic moment measurements, and thermogravimetric analysis (TGA)
      and (DSC). The room temperature effective magnetic moments of complexes are 1.45,
      1.56, 1.62, 2.16, 2.26 and 2.80 B.M. for complexes 3a, 3b, 3c, 4a 4b, and 4c,
      respectively, indicating that the complexes are paramagnetic with considerable
      electronic communication between the two metal centers.

PMID- 22643356
TI  - Influence of chemical extraction conditions on the physicochemical and functional
      properties of polysaccharide gum from durian (Durio zibethinus) seed.
AB  - Durian seed is an agricultural biomass waste of durian fruit. It can be a natural
      plant source of non-starch polysaccharide gum with potential functional
      properties. The main goal of the present study was to investigate the effect of
      chemical extraction variables (i.e., the decolouring time, soaking temperature
      and soaking time) on the physicochemical properties of durian seed gum. The
      physicochemical and functional properties of chemically-extracted durian seed gum
      were assessed by determining the particle size and distribution, solubility and
      the water- and oil-holding capacity (WHC and OHC). The present work revealed that
      the soaking time should be considered as the most critical extraction variable
      affecting the physicochemical properties of crude durian seed gum.

PMID- 22643355
TI  - The coumarin psoralidin enhances anticancer effect of tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL).
AB  - Coumarins are a very common type of secondary plant metabolites with a broad
      spectrum of biological activities. Psoralidin is a naturally occurring
      furanocoumarin isolated from Psoralea corylifolia possessing anticancer and
      chemopreventive properties. Tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) triggers apoptosis in cancer cells with no toxicity toward normal
      tissues. Endogenous TRAIL plays an important role in immune surveillance and
      defence against cancer cells. Coumarins can modulate TRAIL-mediated apoptosis in
      cancer cells. We examined the cytotoxic and apoptotic activities of psoralidin in
      combination with TRAIL on HeLa cancer cells. The cytotoxicity was measured by MTT
      and LDH assays. The apoptosis was detected using annexin V-FITC staining and
      mitochondrial membrane potential was evaluated using DePsipher staining by
      fluorescence microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5)
      expression was analyzed using flow cytometry. Psoralidin enhanced TRAIL-induced
      apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor
      and depolarization of mitochondrial membrane potential. Our study indicated that
      psoralidin augmented the anticancer effects of TRAIL and confirmed a potential
      use of coumarins in cancer chemoprevention.

PMID- 22643359
TI  - Poor asthma control?--then look up the nose. The importance of co-morbid rhinitis
      in patients with asthma.
AB  - Many factors can impair asthma control. One which is frequently overlooked is
      rhinitis. Asthma patients with significant rhinitis are over four times more
      likely to have poorly controlled asthma than those without. Over 80% of patients
      with asthma have rhinitis, which may be allergic or inflammatory/non-allergic.
      Both types of rhinitis share pathophysiological similarities with eosinophilic
      asthma, cause bronchial hyper-reactivity, and are predisposing factors for the
      subsequent development of asthma. Nasal allergen challenge in allergic rhinitis
      results in inflammation in the bronchi as well as the nose, and the reverse is
      also true. This article reviews briefly the evidence for the link between asthma
      and rhinitis, advocates looking for rhinitis when patients present with poorly
      controlled asthma, and provides guidance for the diagnosis and treatment of
      rhinitis.

PMID- 22643360
TI  - Management of co-morbid allergic rhinitis and asthma in a low and middle income
      healthcare setting.

PMID- 22643361
TI  - A practical approach to managing asthma and rhinitis.

PMID- 22643362
TI  - An Impact factor and beyond...

PMID- 22643363
TI  - education@pcrj: the launch of a new initiative for the PCRJ.

PMID- 22643364
TI  - Are higher total serum cholesterol levels associated with better long-term motor
      function after ischemic stroke?
AB  - OBJECTIVES: The objective of the study was to investigate the prognostic role of
      total cholesterol (TC) level on the long-term motor function after ischemic
      stroke. METHODS: One hundred and fourteen patients with ischemic stroke were
      included and divided into high total cholesterol (HTC; TC ?5.18 mmol/l or ?200
      mg/dl) and low total cholesterol (LTC; TC <5.18 mmol/l or <200 mg/dl) groups. The
      motor outcome was evaluated using the motor score of the Fugl-Meyer assessment
      (MFMA) at 2 weeks (baseline), 1, 3, 6, and 12 months after stroke. Prognostic
      factors on the repeated measurements of the MFMA were investigated using the
      linear mixed regression model. RESULTS: The TC, basal ganglion lesion, baseline
      MFMA, first-time stroke, and follow-up time were identified as significant
      predictors for serial MFMA scores. The HTC group had higher MFMA scores than the
      LTC group by 2.72 units (95% confidence interval (CI): 0.17, 5.27, P = 0.037). An
      elevation of one unit of baseline MFMA led to a 0.86 increase (95% CI: 0.82,
      0.90, P < 0.001) of subsequent MFMA scores. Subjects with basal ganglion lesions
      had lower MFMA scores by -3.55 (95% CI: -5.97, -1.14, P = 0.004). DISCUSSION:
      Higher total cholesterol at the acute phase of ischemic stroke is a favorable
      prognostic factor for long-term motor function.

PMID- 22643365
TI  - To be there or not to be there:  is attendance really the question?

PMID- 22643366
TI  - Unintended consequences of duty hours regulation.

PMID- 22643368
TI  - More about who should oversee preparation of the dean's letter.

PMID- 22643367
TI  - More about who should oversee preparation of the dean's letter.

PMID- 22643371
TI  - It's time for faculty to disclose their industry financial ties to medical
      students.

PMID- 22643373
TI  - Commentary:  what role should physician organizations play in addressing social
      justice issues?
AB  - A study by Peek and colleagues in this issue reveals that although racial and
      ethnic health disparities are recognized as a major national challenge, few
      physician organizations with both the influence and ability to change practice
      standards and address disparities appear to be effectively directing their
      resources to mitigate health disparities. In this commentary, the author examines
      the history of U.S. health disparities through the lens of social justice. He
      argues that today, physician organizations have the opportunity to change the
      paradigm of medicine from being a reactive industry to becoming a proactive
      industry through collaborations such as the Commission to End Health Disparities,
      which brings together more than 60 organizations, and the National Medical
      Association's "We Stand With You" program to improve health and combat
      disparities. Physician organizations can also address health disparities through
      advocacy for fair reimbursement policies, funding for pipeline programs to
      increase the diversity of the workforce, diversity in clinical trials, and other
      issues. Health disparities present to us in organized medicine a challenge that
      is cleverly disguised as an immovable object but that is truly a great
      opportunity for innovation, improvement, and growth. Physician organizations have
      a unique opportunity to provide avenues of innovation and accomplishment.

PMID- 22643374
TI  - Commentary:  getting real on addressing health care disparities and other systems
      problems.
AB  - Physician membership organizations vary in the extent of their engagement in
      activities to address health disparities. Increasing engagement of those
      organizations not already highly active in this critical area is, thus, an
      opportunity. Studies that provide definitional contours of key issues, like
      disparities, are necessary and must be iteratively refined. However, parallel
      activities of intervention with measured outcomes to assess the effects of these
      interventions are necessary to truly address major problems in the health care
      system. To date, work in the problem definition category exceeds work toward
      intervention in and mitigation of these problems with measured outcomes. Many
      problems in health care, including disparities, are now sufficiently understood
      that it is time to shift focus toward bold intervention with measured outcomes.
      Optimal approaches that yield superior outcomes generally require collaboration
      across the provider-payer spectrum and the private sectors, including physicians,
      hospitals, insurers, etc. Stakeholders are now free to act in such coordinated
      fashion; it only requires social capital that permits cooperation and compromise.
      Interventions for problems such as health care disparities can be developed in
      the private sector and mirrored by government payers if physicians and
      organizations can get real about collaborating to implement outcomes-based
      initiatives to improve the health of all patients.

PMID- 22643375
TI  - Commentary:  who will help the United States attain the goal of health equity?
AB  - A research report in this issue of Academic Medicine by Peek and colleagues
      describes how physician organizations are mounting different initiatives targeted
      at reducing health disparities. The study emphasizes how these organizations are
      attempting to promote health equity through policies and programs focused on
      education, clinical care, research, and advocacy. They found that 68% of surveyed
      organizations have at least one initiative targeting health disparities.This
      commentary acknowledges the positive trend uncovered by Peek and colleagues which
      characterizes the engagement level of national physician organizations on this
      critical issue, and suggests four ways to enhance future efforts. First, health
      equity should be linked to overall quality of care and emerging initiatives aimed
      at transforming the delivery of health care. Second, the effect of such efforts
      can be magnified by evaluating what works and sharing best practices. Third,
      interventions must be targeted at institutions as well as individual physicians.
      Finally, it should be emphasized that the driving rationale for physicians to
      strive for health equity is the ethical imperative to promote justice in health
      care.

PMID- 22643376
TI  - Commentary: choice--the need for a thorough and open discussion: implications for
      academic health centers.
AB  - The reality is that choice in health care may be limited or substantially
      curtailed in the future. To imply that the U.S. health care system can achieve
      the needed cost savings without such restrictions is not productive and may be
      potentially deceptive. Continued unfiltered, unlimited choice will only continue
      to drive more utilization and costs. Academic health centers (AHCs) should take a
      leadership role in expanding the public dialogue regarding health care reform and
      its likely need to limit choice at some level while preparing for the inevitable
      related evolution of AHCs' core clinical programs, relationships, and strategies.

PMID- 22643377
TI  - The God complex.

PMID- 22643378
TI  - Medicine and the arts. The practice [William Hogarth's Gin Lane] by Henry N.
      Claman. Commentary.

PMID- 22643379
TI  - If you can't handle death ...

PMID- 22643380
TI  - Governance and assessment in a widely distributed medical education program in
      Australia.
AB  - The learning objectives, curriculum content, and assessment standards for
      distributed medical education programs must be aligned across the health care
      systems and community contexts in which their students train. In this article,
      the authors describe their experiences at Monash University implementing a
      distributed medical education program at metropolitan, regional, and rural
      Australian sites and an offshore Malaysian site, using four different
      implementation models. Standardizing learning objectives, curriculum content, and
      assessment standards across all sites while allowing for site-specific
      implementation models created challenges for educational alignment. At the same
      time, this diversity created opportunities to customize the curriculum to fit a
      variety of settings and for innovations that have enriched the educational system
      as a whole.Developing these distributed medical education programs required a
      detailed review of Monash's learning objectives and curriculum content and their
      relevance to the four different sites. It also required a review of assessment
      methods to ensure an identical and equitable system of assessment for students at
      all sites. It additionally demanded changes to the systems of governance and the
      management of the educational program away from a centrally constructed and
      mandated curriculum to more collaborative approaches to curriculum design and
      implementation involving discipline leaders at multiple sites.Distributed medical
      education programs, like that at Monash, in which cohorts of students undertake
      the same curriculum in different contexts, provide potentially powerful research
      platforms to compare different pedagogical approaches to medical education and
      the impact of context on learning outcomes.

PMID- 22643381
TI  - AM last page. The World Federation for Medical Education (WFME).

PMID- 22643383
TI  - Proactive action preparation: seeing action preparation as a continuous and
      proactive process.
AB  - In this paper, we aim to elucidate the processes that occur during action
      preparation from both a conceptual and a computational point of view. We first
      introduce the traditional, serial model of goal-directed action and discuss from
      a computational viewpoint its subprocesses occurring during the two phases of
      covert action preparation and overt motor control. Then, we discuss recent
      evidence indicating that these subprocesses are highly intertwined at
      representational and neural levels, which undermines the validity of the serial
      model and points instead to a parallel model of action specification and
      selection. Within the parallel view, we analyze the case of delayed choice,
      arguing that action preparation can be proactive, and preparatory processes can
      take place even before decisions are made. Specifically, we discuss how prior
      knowledge and prospective abilities can be used to maximize utility even before
      deciding what to do. To support our view, we present a computational
      implementation of (an approximated version of) proactive action preparation,
      showing its advantages in a simulated tennis-like scenario.

PMID- 22643382
TI  - Holoprosencephaly-polydactyly/pseudotrisomy 13:  a presentation of two new cases
      and a review of the literature.
AB  - Patients with a combination of holoprosencephaly and polydactyly, but with
      apparently normal chromosomes, may be clinically diagnosed with holoprosencephaly
      polydactyly syndrome (HPS), also termed pseudotrisomy 13. However, the criteria
      for HPS have been controversial since the advent of the diagnostic term, and a
      clear understanding of the condition lacks definitive delineation. We review the
      historical and current perspectives on the condition and analyze findings in 40
      patients with apparent HPS, including cases from the literature and two
      previously unreported patients. Overall, our analysis suggests previously
      unrecognized trends in patients diagnosed with HPS. Specifically, there appears
      to be a higher prevalence of visceral anomalies, most significantly cardiac and
      genitourinary, but also with increased gastrointestinal, pulmonary, adrenal,
      skeletal, and renal abnormalities, in patients with HPS. Although these visceral
      anomalies may not be essential for the identification of HPS, clinicians should
      be aware of the presence of such characteristics in these patients to optimize
      management and help establish etiologies.

PMID- 22643384
TI  - Targeting breast cancer vaccines to dendritic cells: improved immunological
      responses with less protein?
AB  - The central goal of cancer immunotherapy is to control tumors through the
      mobilization of the patient's immune system. Vaccines targeting the Her2/neu
      proto-oncogene have been tested with some early encouraging responses in breast
      cancer. However, a more effective set of vaccines targeting specific immune cell
      subtypes may provide a more potent means to stimulate anti-tumor immunity.
      Dendritic cell-specific antibodies fused with the Her2/neu protein proved
      effective at generating immune responses in preclinical models. Importantly, only
      low amounts of protein vaccine were required to generate this response, which has
      potentially significant implications for the future clinical development of
      Her2/neu-targeted vaccines and other vaccine targets.

PMID- 22643385
TI  - Appropriate use of lumbar imaging for evaluation of low back pain.
AB  - Use of lumbar spine imaging, particularly advanced imaging, continues to grow
      rapidly in the United States. Many lumbar spine imaging tests are obtained in
      patients who have no clinical symptoms or risk factors suggesting a serious
      underlying condition, yet evidence shows that this routine imaging is not
      associated with benefits, exposes patients to unnecessary harms, and increases
      costs. This article reviews current trends and practice patterns in lumbar spine
      imaging, direct and downstream costs, benefits and harms, current
      recommendations, and potential strategies for reducing imaging overuse.

PMID- 22643386
TI  - Spine segmentation and enumeration and normal variants.
AB  - This article provides a comprehensive review of spine segmentation and
      enumeration. This important and relatively underappreciated issue, when
      neglected, frequently results in confusion in vertebral numbering and ultimately
      may result in wrong segment interventions. The authors supplement this topic with
      a discussion of normal variants.

PMID- 22643387
TI  - Physiologic imaging of the spine.
AB  - Spine imaging poses unique challenges to radiologist and clinician. The dynamic
      nature of the spine and its mobility across multiple segments is difficult to
      depict with any single imaging modality. Supine imaging fails to demonstrate the
      physiologic effects seen with axial load, physiologic posture or positional
      change. Physiologic imaging begins with standing radiographs. Advanced techniques
      include axial loading devices on conventional CT or MRI, dynamic (upright) MRI
      and stereoradiography (EOS). These techniques may unmask dynamic pathology that
      otherwise would be hidden on conventional supine imaging. Caution must be
      exercised where such techniques (upright MRI) reduce sensitivity to sinister
      disease.

PMID- 22643388
TI  - Degenerative joint disease of the spine.
AB  - Degenerative changes are the manifestations of metabolic disturbances in the
      matrix of intervertebral disks and zygapophysial joints. Genetic factors and
      physical loading contribute, but the strongest correlation is with age.
      Degenerative changes lack any significant correlation with spinal pain.
      Therefore, they do not constitute a diagnosis. Internal disk disruption is a
      distinctive condition that is independent of degeneration and age. Its
      biophysical and morphologic features correlate with back pain, as do its
      manifestations on magnetic resonance imaging.

PMID- 22643389
TI  - Imaging the intervertebral disk: age-related changes, herniations, and radicular
      pain.
AB  - The articulations of the spinal motion segment, the intervertebral disk, and the
      zygapophyseal joints, inevitably undergo age-related changes. This article
      focuses on the intervertebral disk, specifically when fissures sufficiently
      weaken the posterior annulus so as to allow herniation of nuclear material into
      the outer annular structure as a contained protrusion or breach the annulus and
      pass into the epidural space as an extrusion. This article examines the imaging
      of the age-related changes of the disk and disk herniation: nomenclature, the
      reliability and relative merits of imaging modalities, the imaging natural
      history of disk herniations, and, most importantly, the clinical significance.

PMID- 22643390
TI  - Imaging of spinal stenosis: neurogenic intermittent claudication and cervical
      spondylotic myelopathy.
AB  - Spinal stenosis in either the cervical or lumbar spinal segments is one of the
      most common indications for spine imaging and intervention, particularly among
      the elderly. This article examines the pathophysiology and imaging of the
      corresponding clinical syndromes, cervical spondylotic myelopathy or neurogenic
      intermittent claudication. The specificity fault of spine imaging is readily
      evident in evaluation of spinal stenosis, as many patients with anatomic cervical
      or lumbar central canal narrowing are asymptomatic. Imaging also may be
      insensitive to dynamic lesions. Those imaging features that identify symptomatic
      patients, or predict response to interventions, are emphasized.

PMID- 22643391
TI  - Lumbar diskogenic pain, provocation diskography, and imaging correlates.
AB  - Diskogenic pain refers to pain mediated by the intrinsic innervation of the
      intervertebral disk. It is experienced as pain centered at the symptomatic spine
      segment (axial pain) without radicular features or radiculopathy. There is no
      pathoanatomic gold standard; histologic examination cannot identify a painful
      disk. The current reference standard for diskogenic pain is provocation
      diskography. This article reviews diskogenic pain, the history of provocation
      diskography, and its current use in the diagnosis of lumbar diskogenic pain. The
      extensive literature describing imaging features which may predict a positive
      diskogram, and allow non-invasive diagnosis of diskogenic pain, is examined.

PMID- 22643392
TI  - Imaging of posterior element axial pain generators: facet joints, pedicles,
      spinous processes, sacroiliac joints, and transitional segments.
AB  - The role of the posterior elements in generating axial back and neck pain is well
      established; the imaging detection of posterior element pain generators remains
      problematic. Morphologic imaging findings have proved to be nonspecific and are
      frequently present in asymptomatic patients. Edema, inflammation, and
      hypervascularity are more specific for sites of pain generation, but are often
      overlooked by imagers if physiologic imaging techniques such as fat-suppressed T2
      or contrast-enhanced T1-weighted magnetic resonance imaging, radionuclide bone
      scanning with single-photon emission computed tomography (CT), or (18)F
      fluorodeoxyglucose positron emission tomography combined with CT are not used.

PMID- 22643393
TI  - Imaging the postoperative spine.
AB  - Imaging assessment of the postoperative spine is complex and depends on many
      factors. Postoperative imaging studies evaluate the position of implants,
      adequacy of decompression, fusion status, and potential complications. This
      article provides a review of various imaging techniques, with their advantages
      and disadvantages, for the evaluation of the postoperative spine. It also gives
      an overview of normal and abnormal postoperative appearances of the spine as seen
      via various modalities, with an emphasis on postoperative complications.

PMID- 22643394
TI  - Imaging of spine neoplasm.
AB  - Although most often back pain is of benign origin, it can occasionally be a
      harbinger of a more serious spinal condition, including spine neoplasm. Knowledge
      of the typical clinical history of spinal tumors and an understanding of the
      innervation of the spine and surrounding supporting structures may allow us to
      better understand when to pursue advanced imaging in the evaluation of spinal
      pain syndromes. Many radiologists have divided the differential diagnosis of
      neoplasms of the spine into compartments. These compartments include the
      extradural compartment, intradural/extramedullary compartment, and the
      intramedullary compartment.

PMID- 22643395
TI  - Imaging of spine infection.
AB  - This article reviews the imaging and relevant clinical details of infection of
      the extradural spine. Spine infections are increasing in incidence and in
      frequency of diagnosis. They are clinically important despite their relative
      rarity, because they may be life-threatening, and because early diagnosis leads
      to improved outcomes. The focus is on pyogenic spondylodiscitis. The also
      typically pyogenic conditions of epidural and subdural abscess, facet joint
      infection, and pyomyositis are discussed. Nonpyogenic, granulomatous infections
      are also addressed. Magnetic resonance imaging is emphasized. The radiologist's
      role in performing minimally invasive sampling procedures is highlighted.

PMID- 22643396
TI  - Imaging of stress fractures of the spine.
AB  - Back pain caused by stress fractures, fatigue, or insufficiency, affects varied
      patient populations based on the level of physical activity and bone mineral
      density. Stress fractures may involve the vertebral body, pars interarticularis,
      and the pedicle; often overlooked are stress fractures of the sacrum or bony
      pelvis, which can mimic pain of spinal origin and delay diagnosis. The choice of
      optimal imaging (radiographs, nuclear medicine, magnetic resonance imaging, and
      computed tomography) also depends on the patient population under study and the
      clinically suspected diagnosis. The diagnosis typically determines which imaging
      modality is best to follow healing or progression.

PMID- 22643397
TI  - Imaging of dural arteriovenous fistula.
AB  - Spinal dural arterial venous fistulas (SDAVFs) are the most common vascular
      malformation of the spine. They typically present in elderly men with slowly
      progressive myelopathic symptoms. They often go undiagnosed because of the
      similar clinical presentation of more common entities in this age group.
      Radiologists should be familiar with the imaging features of this entity, with
      the surgical and angiographic interventions, and with the expected postprocedural
      radiographic appearance. This article reviews spinal vascular anatomy, the
      radiographic appearances of SDAVF, techniques for finding the SDAVF, clinical
      presentations, treatment options, and postprocedural radiographic appearances of
      the spinal cord.

PMID- 22643398
TI  - Imaging of the seronegative spondyloarthopathies.
AB  - The seronegative spondyloarthropathies are a diverse group of conditions most
      commonly affecting the axial spine, often presenting with back pain of an
      inflammatory nature. The primary unifying feature of these disorders is
      sacroiliitis. The distinction between subtypes of spondyloarthritis is based on
      genotype (HLA-B27 positivity as in ankylosing spondylitis), peripheral
      manifestations of disease (psoriatic and reactive arthritis), and factors such as
      age, gender, and comorbidity. Although radiography has long been used to diagnose
      the spondyloarthropathies, advanced imaging with magnetic resonance is better
      able to diagnose these disorders at their earliest stages and monitor disease
      modifying therapies.

PMID- 22643399
TI  - Spine imaging.

PMID- 22643401
TI  - Phosphorus recovery as struvite from eutropic waters by XDA-7 resin.
AB  - Phosphorus releases into aquatic environment and its subsequent contribution to
      eutrophication have resulted in a widespread global pollution issue. However,
      phosphorus is a non-renewable source. The potential supplies of phosphorus are
      decreasing worldwide. Therefore, removal and recovery of phosphorus from the
      eutropic waters is important, emergent and necessary. In this research,
      experiments for recovering phosphate from eutropic waters by anion exchange
      combined with struvite precipitation were conducted. The results indicated that
      the prepared XDA-7 resin was an effective adsorbent for phosphate. The adsorption
      isotherm of XDA-7 resin was found to be a modified Freundlich type. The maximum
      phosphate adsorption (20.9 mg/g) occurred in the pH range of 6.0-8.0. Phosphate
      adsorbed on the XDA-7 resin was effectively desorbed with 8% NaCl solution, and
      the resin was able to be regenerated with 3% NaClO and 4% NaOH solutions.
      Phosphate desorbed from the resin was recovered as magnesium ammonium phosphate
      (struvite). The obtained struvite was analyzed by acid dissolution method,
      scanning electron microscope (SEM) and Fourier transform infrared spectroscopy
      (FTIR). The struvite precipitate was found to be 75.8% in purity, a high-value
      fertilizer.

PMID- 22643402
TI  - Application of an anaerobic hybrid reactor for petrochemical effluent treatment.
AB  - An anaerobic hybrid reactor (UASB/Filter) was used for petrochemical wastewater
      treatment in mesophilic conditions. The seeded flocculent sludge from a UASB
      plant treating dairy wastewater, acclimatized to the petrochemical wastes in a
      two-stage operation. After start up, under steady-state conditions, experiments
      were conducted at OLRs of between 0.5 and 24 kg TCOD m(-3) d(-1), hydraulic
      retention times (HRT) of 4-48 h and up-flow velocities 0.021-0.25 mh(-1). Removal
      efficiencies in the range of 42-86% were achieved at feed TCOD concentrations of
      1,000-4,000 mg L(-1). The results of reactor performance at different operational
      conditions and its relations are presented and discussed in this paper. Then, the
      obtained data are used for determination of kinetic models. The results showed
      that a second-order model and a modified Stover-Kincannon model were the most
      appropriate models for this reactor. Finally, the biogas production data were
      used for the determination of biogas production kinetics.

PMID- 22643400
TI  - Neural substrates for the distinct effects of presynaptic group III metabotropic
      glutamate receptors on extinction of contextual fear conditioning in mice.
AB  - The group III metabotropic glutamate (mGlu) receptors mGlu7 and mGlu8 are
      receiving increased attention as potential novel therapeutic targets for anxiety
      disorders. The effects mediated by these receptors appear to result from a
      complex interplay of facilitatory and inhibitory actions at different brain sites
      in the anxiety/fear circuits. To better understand the effect of mGlu7 and mGlu8
      receptors on extinction of contextual fear and their critical sites of action in
      the fear networks, we focused on the amygdala. Direct injection into the
      basolateral complex of the amygdala of the mGlu7 receptor agonist AMN082
      facilitated extinction, whereas the mGlu8 receptor agonist (S)-3,4-DCPG sustained
      freezing during the extinction acquisition trial. We also determined at the
      ultrastructural level the synaptic distribution of these receptors in the basal
      nucleus (BA) and intercalated cell clusters (ITCs) of the amygdala. Both areas
      are thought to exert key roles in fear extinction. We demonstrate that mGlu7 and
      mGlu8 receptors are located in different presynaptic terminals forming both
      asymmetric and symmetric synapses, and that they preferentially target neurons
      expressing mGlu1alpha receptors mostly located around ITCs. In addition we show
      that mGlu7 and mGlu8 receptors were segregated to different inputs to a
      significant extent. In particular, mGlu7a receptors were primarily onto
      glutamatergic afferents arising from the BA or midline thalamic nuclei, but not
      the medial prefrontal cortex (mPFC), as revealed by combined anterograde tracing
      and pre-embedding electron microscopy. On the other hand, mGlu8a showed a more
      restricted distribution in the BA and appeared absent from thalamic, mPFC and
      intrinsic inputs. This segregation of mGlu7 and mGlu8 receptors in different
      neuronal pathways of the fear circuit might explain the distinct effects on fear
      extinction training observed with mGlu7 and mGlu8 receptor agonists. This article
      is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.

PMID- 22643403
TI  - Direct precipitation on demand at large Scandinavian WWTPs reduces the effluent
      phosphorus load.
AB  - On demand use of direct precipitation of wastewater has been successfully
      implemented at several large Scandinavian wastewater treatment plants (WWTPs) as
      a cost-efficient method of treating wastewater bypassing secondary treatment.
      During wet weather situations or when the capacity of secondary treatment is
      reduced excess wastewater can be treated through efficient direct precipitation.
      This increases the total capacity of the WWTP to remove phosphorus during these
      periods. This treatment strategy allows the WWTPs to meet stringent effluent
      phosphorus limits without extending secondary treatment of the main plant,
      despite high wet weather flows. The gain in terms of reduced phosphorus emissions
      varies depending on local conditions such as climate, collection system and
      secondary treatment capacity. It also varies from year to year depending on the
      weather and reductions of capacity due to planned refurbishing or unplanned
      breakdown of equipment. Operating chemical precipitation on demand has proved to
      contain challenges to operation and organisation of the WWTP. These challenges
      include logistics of start-up, training of staff and maintaining the system
      between occasions of operation. Sufficient up-stream storage capacity, reliable
      weather forecasts and good contracts with suppliers of chemicals are keys of
      success.

PMID- 22643404
TI  - Frequency analysis of river water quality using integrated urban wastewater
      models.
AB  - In recent years integrated models have been developed to simulate the entire
      urban wastewater system, including urban drainage systems, wastewater treatment
      plants, and receiving waterbodies. This paper uses such an integrated urban
      wastewater model to analyze the frequency of receiving water quality in an urban
      wastewater system with the aim of assessing the overall system performance during
      rainfall events. The receiving water quality is represented by two indicators:
      event mean dissolved oxygen (DO) concentration and event mean ammonium
      concentration. The compliance probability of the water quality indicators
      satisfying a specific threshold is used to represent the system performance, and
      is derived using the rainfall events from a series of 10 years' rainfall data. A
      strong correlation between the depth of each rainfall event and the associated
      volume of combined sewer overflow (CSO) discharges is revealed for the case study
      catchment, while there is a low correlation between the intensity/duration of the
      rainfall event and the volume of the CSO discharges. The frequency analysis
      results obtained suggest that the event mean DO and ammonium concentrations have
      very different characteristics in terms of compliance probabilities at two
      discharging points for CSO and wastewater treatment plant effluent, respectively.
      In general, the simulation results provide an understanding of the performance of
      the integrated urban wastewater system and can provide useful information to
      support water quality management.

PMID- 22643405
TI  - The distribution, accumulation and potential source of seldom monitored trace
      elements in sediments of Beijiang River, South China.
AB  - A geochemical study of Beijiang River sediments was carried out to analyze the
      concentrations, distribution, accumulation and potential sources of the seldom
      monitored trace elements (SMTEs: Sc, V, Co, Ga, Y, Sn and Sb). The mean
      concentrations of Sc, V, Co, Ga, Y, Sn and Sb were 8.2, 60.3, 9.6, 17.2, 28.6,
      85.6 and 39.0 mg/kg, respectively. The concentrations of the SMTEs, together with
      their spatial distribution showed that the SMTEs were mainly due to anthropogenic
      inputs from the metal smelting industries and local mining activities in the
      upper region of the river. The assessment by geoaccumulation index indicates that
      Sc, V, Co, Ga and Y are at the unpolluted level, Sn is at the 'strongly
      contaminated' level, and Sb is at the 'extremely contaminated' level. The
      pollution level of the SMTEs is: Sb > Sn > Y > Ga > Co > V > Sc. The results of
      correlation analysis and principal component analysis indicated the Sn and Sb
      were positively correlated with each other, indicating a common source in
      sediments. In conclusion, our results indicate that the sediments in Beijiang
      River have been severely contaminated by Sn and Sb.

PMID- 22643406
TI  - Characterization of microbial community structures and their activities in single
      anaerobic granules by beta imaging, microsensors and fluorescence in situ
      hybridization.
AB  - The spatial distribution of microorganisms and their in situ activities in
      anaerobic granules were investigated by fluorescence in situ hybridization
      (FISH), beta imaging and microsensors. FISH results revealed a layered structure
      of microorganisms in the granule, where Chloroflexi was present in the outermost
      layer, Smithella spp. and Syntrophobacter spp. were found in a depth of ca. 100
      MUm, and Archaea was restricted to the inner layer (below ca. 300 MUm from the
      surface). Substrate uptake patterns elucidated by beta imaging demonstrated that
      glucose uptake was highest at 50 MUm depth, whereas propionate uptake had a peak
      at 200 MUm depth. In addition, microsensor measurements revealed that acid was
      produced mainly at 100 MUm depth and H(2) production was detected at a depth from
      100 to 200 MUm. H(2) consumption and corresponding CH(4) production were found
      below 200 MUm from the surface. Direct comparison of these results implied
      sequential degradation of complex organic compounds in anaerobic granules;
      Chloroflexi contributed to fermentation of organic compounds and acid production
      in the outermost layer, volatile fatty acids were oxidized and H(2) was produced
      mainly by Smithella spp. and Syntrophobacter spp. at a depth from 100 to 200 MUm,
      and Archaea produced CH(4) below ca. 300 MUm from the surface.

PMID- 22643408
TI  - SSUIS - a research model for predicting suspended solids loads in stormwater
      runoff from urban impervious surfaces.
AB  - Suspended solids from urban impervious surfaces (SSUIS) is a spreadsheet-based
      model that predicts the mass loading of suspended solids (SS) in stormwater
      runoff generated from impervious urban surfaces. The model is intended to be a
      research tool and incorporates several particle accumulation and washoff
      processes. Development of SSUIS is based on interpretation of storm event data
      obtained from a galvanised iron roof, a concrete car park and a bitumen road
      located in Toowoomba, Australia. SSUIS is a source area model that tracks the
      particle mass balance on the impervious surface and within its lateral drain to a
      point of discharge. Particles are separated into two groups: free and detained,
      depending on the rainfall energy required for surface washoff. Calibration and
      verification of SSUIS against the Toowoomba SS data yielded R(2) values ranging
      from 0.60 to 0.98. Parameter sensitivity analysis and an example of how SSUIS can
      be applied to predict the treatment efficiency of a grass swale are also
      provided.

PMID- 22643407
TI  - Biodegradation of o-nitrophenol by aerobic granules with glucose as co-substrate.
AB  - Aerobic granules to treat wastewater containing o-nitrophenol were successfully
      developed in a sequencing batch reactor (SBR) using activated sludge as inoculum.
      Stable aerobic granules were obtained with a clearly defined shape and diameters
      ranging from 2 to 6 mm after 122 days of operation. The integrity coefficient
      (IC) and granules density was found to be 98% and 1,054 kg m(-3) respectively.
      After development of aerobic granules, o-nitrophenols were successfully degraded
      to an efficiency of 78% at a concentration of 70 mg L(-1). GC-MS study revealed
      that the biodegradation of o-nitrophenol occurred via catechol via nitrobenzene
      pathway. Specific o-nitrophenol biodegradation rates followed the Haldane model
      and the associated kinetic parameters were found as follows: V(max) = 3.96 g o
      nitrophenol g(-1)VSS(-1)d(-1), K(s) = 198.12 mg L(-1), and K(i) = 31.16 mg L(-1).
      The aerobic granules proved to be a feasible and effective way to degrade o
      nitrophenol containing wastewater.

PMID- 22643409
TI  - Dynamic mass balancing for wastewater treatment data quality control using CUSUM
      charts.
AB  - Mass balancing is a widely used tool for data quality control in wastewater
      treatment. It can effectively detect systematic errors in data. To overcome the
      limitations of the mean balancing error as a measure of data quality, a well
      established method for statistical process control (the CUSUM chart) is adopted
      for application on the error vector of balancing data. Two examples show how time
      periods with stable low mass balancing errors can be detected by the method. The
      detectability of such time periods depends on the variability of the balancing
      error which is an important measure for the precision of the data.

PMID- 22643410
TI  - Contaminant removal and hydraulic conductivity of laboratory rain garden systems
      for stormwater treatment.
AB  - In order to evaluate the influence of substrate composition on stormwater
      treatment and hydraulic effectiveness, mesocosm-scale (180 L, 0.17 m(2))
      laboratory rain gardens were established. Saturated (constant head) hydraulic
      conductivity was determined before and after contaminant (Cu, Zn, Pb and
      nutrients) removal experiments on three rain garden systems with various
      proportions of organic topsoil. The system with only topsoil had the lowest
      saturated hydraulic conductivity (160-164 mm/h) and poorest metal removal
      efficiency (Cu <= 69.0% and Zn <= 71.4%). Systems with sand and a sand-topsoil
      mix demonstrated good metal removal (Cu up to 83.3%, Zn up to 94.5%, Pb up to
      97.3%) with adequate hydraulic conductivity (sand: 800-805 mm/h, sand-topsoil:
      290-302 mm/h). Total metal amounts in the effluent were <50% of influent amounts
      for all experiments, with the exception of Cu removal in the topsoil-only system,
      which was negligible due to high dissolved fraction. Metal removal was greater
      when effluent pH was elevated (up to 7.38) provided by the calcareous sand in two
      of the systems, whereas the topsoil-only system lacked an alkaline source.
      Organic topsoil, a typical component in rain garden systems, influenced pH,
      resulting in poorer treatment due to higher dissolved metal fractions.

PMID- 22643411
TI  - Comparison studies of unsaturated flow below annual and perennial plants.
AB  - Values of unsaturated water content determined with neutron moisture measurements
      (NMM) reveal different water profiles below different plantings. In the extremes,
      calibration requires a linear and logarithmic response (using the Lambert-W
      function) along with the normal submersion in a drum of water. Nevertheless a
      post-calibration with a hydraulic push sampler was used for confirmation. Data
      were collected at six pastures near the Western Australia coast near Geraldton,
      with four replicates through the profile. The sites have mostly sandy soils and
      receive 300-500 mm of rainfall annually. Findings generally showed that, if there
      was sufficient water, as in 2006, the perennials were able to use the water
      evenly throughout the vertical profile. Otherwise, with low rainfall, as in 2009,
      perennials struggle to survive and use less water than the annuals. Modelling of
      the soil water movement, plant growth and calibration/recalibration is and will
      be used to get a maximum likehood fit. Clearly, in desert conditions and little
      or no vegetation, rainfall tends to build up deep in the profile, increase
      salinity in groundwater, and create waterlogging. Any vegetation is helpful;
      perennials more so; provided they have sufficient water and are not significantly
      harvested.

PMID- 22643412
TI  - Flocculation mechanism by a novel combined aluminum-ferrous-starch flocculant
      (CAFS).
AB  - A combined flocculant (CAFS) was prepared with Al(2)(SO(4))(3).18H(2)O,
      FeSO(4).7H(2)O and starch. The flocculation mechanism of reactive brilliant red X
      3B was studied. The results showed that CAFS was a cationic polymeric flocculant
      with high charge density, and its mesh starch chains grafted polyaluminum and
      polyferrous. At the preliminary stage, the main flocculation mechanism was
      adsorption and charge neutralization. At a later stage, the high molecular weight
      and flexible linear chains of CAFS initiated bridge-aggregation and sweep
      flocculation. Moreover, the zeta potential and dynamic changes of flocs were
      closely related to flocculant dosages and the pH. The optimum dosage of CAFS and
      pH value were 0.990 mg/L and 5.0. Taken together, these results suggested CAFS as
      a novel flocculant in water treatment, with good results for the studied
      conditions.

PMID- 22643413
TI  - Degradation of azo dye with dirhodium(II) caprolactamate as heterogeneous
      catalyst.
AB  - The kinetics of the oxidative degradation of an azo dye Metanil Yellow (MY) was
      investigated in aqueous solution using dirhodium(II) caprolactamate,
      Rh(2)(cap)(4), as a catalyst in the presence of H(2)O(2) as oxidizing agent. The
      reaction process was followed by UV/Vis spectrophotometer. The decolorization and
      degradation kinetics were investigated and both followed a pseudo-first-order
      kinetic with respect to the [MY]. The effects of various parameters such as
      H(2)O(2) and dye concentrations, the amount of catalyst and temperature have been
      studied. The studies show that Rh(2)(cap)(4) is a very effective catalyst for the
      formation of hydroxyl radicals HO(*) which oxidized and degraded about 92% of MY
      into CO(2) and H(2)O after 24 h as measured by total carbon analyzer.

PMID- 22643414
TI  - Electrochemical treatment of Baker's yeast wastewater containing melanoidin:
      optimization through response surface methodology.
AB  - Effluents from Baker's yeast production plant contain a high percentage of color
      and a large amount of organic load. In the present study, Baker's yeast
      wastewater (BYW) is treated with the electrocoagulation (EC) process using Al
      electrodes. Operating parameters (pH, current density, color intensity and
      operating time) are optimized by response surface methodology (RSM). Quadratic
      models are developed for the responses which are removal efficiencies of color,
      chemical oxygen demand (COD) and total organic carbon (TOC) and operating cost
      (OC). Optimum operating parameters and responses are determined as initial pH
      5.2, current density of 61.3 A/m(2) and operation time of 33 min, and 71% of
      color, 24% of COD, 24% of TOC removal efficiencies and OC of 0.869 ?/m(3),
      respectively. The quadratic model fits for all responses very well with R(2)
      (>0.95). This paper clearly shows that RSM is able to optimize the operating
      parameters to maximize the color, COD and TOC removal efficiencies and minimize
      the OC.

PMID- 22643415
TI  - Removal of methylene blue from aqueous solution using wine-processing waste
      sludge.
AB  - Dye wastewaters usually contain toxins and high chroma, making them difficult to
      treat with biological methods. The adsorption process plays an important role in
      removing dyes from wastewaters. This study aimed to explore the methylene blue
      (MB) adsorption mechanism by wine-processing waste sludge (WPWS). The WPWS
      contains a high cation-exchange capacity (64.2 cmol(c) kg(-1)) and organic matter
      (52.8%). The parameters affecting MB adsorption included pH, initial
      concentration of MB, reaction temperature, particle size and dosage of WPWS. The
      WPWS adsorption isotherms of MB were only well described by Langmuir adsorption
      isotherm. The maximum adsorption capacity (Q(m)) of MB was 285.7 mg g(-1) at 25 
      degrees C. The activation energy determined by Arrhenius equation is 29.995 kJ
      mol(-1). Under steady-state reaction conditions, the Gibb free energy (DeltaG
      degrees ) ranged from -24.607 to -27.092 kJ mol(-1) and DeltaH degrees  was 
      8.926 kJ mol(-1), indicating that lower reaction temperature would favor MB
      adsorption. Therefore, MB adsorption by WPWS was a spontaneous, exothermic and
      physisorption reaction.

PMID- 22643416
TI  - Evaluation of inhibition relief operations for mesophilic anaerobic bio
      liquefaction of lincomycin manufacturing biowaste.
AB  - Owing to high levels of residual antibiotics, antibiotic manufacturing waste is
      hazardous to the environment. As a result, such wastes are usually treated by
      expensive incineration. The high organic content of antibiotic manufacturing
      biowaste suggests its feasibility for anaerobic treatment, but the presence of
      ammonia and antibiotics in the waste may be inhibitory factors. After evaluating
      the peak concentrations of volatile fatty acids (VFAs), ammonia and lincomycin in
      10 d bio-liquefaction, different methods for the removal of ammonia from
      hydrolysate and removal of lincomycin from biowaste were employed to relieve
      ammonia and lincomycin inhibition respectively. Prior to ammonia elimination on
      the tenth day, 38.0% of the organic carbon was degraded into hydrolysate. Water
      replacement, struvite precipitation and nitrogen stripping removed 100, 76 and
      30% of the ammonia, respectively. The hydrolysate obtained from the water
      replacement could be immediately utilized for liquefaction. Lincomycin elution
      through butanol and water prior to liquefaction removed a large amount of
      carbohydrate and protein, resulting in poor liquefaction efficiency. The residual
      lincomycin in the bio-liquefaction process could be co-treated with lincomycin
      manufacturing wastewater, which made it suitable for the treatment of lincomycin
      manufacturing biowaste.

PMID- 22643417
TI  - The effect of certain biochemical factors on well clogging under suboxic and
      mildly anoxic conditions.
AB  - Research conducted at the Belgrade Groundwater Source in Serbia has shown that
      significant well screen clogging processes take place under reduced oxic and
      initial anoxic conditions. Criteria for the prevention, or deceleration, of
      clogging are becoming more relevant to well ageing, compared with classical,
      mechanical clogging criteria and the permissible entrance velocities derived from
      them. The research project was later expanded to encompass other alluvial
      sources, which feature distinct oxic conditions. This paper presents some of the
      outcomes of this project, which shed light on the correlation between certain
      important indicators of well screen clogging (such as the redox potential and
      iron concentration) and the rate of increase in local hydraulic resistance at the
      wells.

PMID- 22643418
TI  - Effect of integrating straw into agricultural soils on soil infiltration and
      evaporation.
AB  - Soil water movement is a critical consideration for crop yield in straw
      integrated fields. This study used an indoor soil column experiment to determine
      soil infiltration and evaporation characteristics in three forms of direct straw
      integrated soils (straw mulching, straw mixing and straw inter-layering). Straw
      mulching is covering the land surface with straw. Straw mixing is mixing straw
      with the top 10 cm surface soil. Then straw inter-layering is placing straw at
      the 20 cm soil depth. There are generally good correlations among the mulch
      integration methods at p < 0.05, and with average errors/biases <10%. Straw
      mixing exhibited the best effect in terms of soil infiltration, followed by straw
      mulching. Due to over-burden weight-compaction effect, straw inter-layering
      somehow retarded soil infiltration. In terms of soil water evaporation, straw
      mulching exhibited the best effect. This was followed by straw mixing and then
      straw inter-layering. Straw inter-layering could have a long-lasting positive
      effect on soil evaporation as it limited the evaporative consumption of deep soil
      water. The responses of the direct straw integration modes to soil infiltration
      and evaporation could lay the basis for developing efficient water-conservation
      strategies. This is especially useful for water-scarce agricultural regions such
      as the arid/semi-arid regions of China.

PMID- 22643419
TI  - Impact of sewer condition on urban flooding: an uncertainty analysis based on
      field observations and Monte Carlo simulations on full hydrodynamic models.
AB  - In-sewer defects are directly responsible for affecting the performance of sewer
      systems. Notwithstanding the impact of the condition of the assets on
      serviceability, sewer performance is usually assessed assuming the absence of in
      sewer defects. This leads to an overestimation of serviceability. This paper
      presents the results of a study in two research catchments on the impact of in
      sewer defects on urban pluvial flooding at network level. Impacts are assessed
      using Monte Carlo simulations with a full hydrodynamic model of the sewer system.
      The studied defects include root intrusion, surface damage, attached and settled
      deposits, and sedimentation. These defects are based on field observations and
      translated to two model parameters (roughness and sedimentation). The calculation
      results demonstrate that the return period of flooding, number of flooded
      locations and flooded volumes are substantially affected by in-sewer defects.
      Irrespective of the type of sewer system, the impact of sedimentation is much
      larger than the impact of roughness. Further research will focus on comparing
      calculated and measured behaviour in one of the research catchments.

PMID- 22643420
TI  - The influence of salinity and ammonium levels on amoA mRNA expression of ammonia
      oxidizing prokaryotes.
AB  - This study investigated the influence of salinity and ammonium levels on ammonia
      oxidizing bacteria (AOB) and archaea (AOA) by monitoring their amo subunit A
      (amoA) messenger RNA (mRNA) expression. The aerobic mini-continuous stirred-tank
      reactors (mini-CSTRs) were operated for 48 h under different salinity or ammonium
      levels. Quantification of archaeal and bacterial amoA mRNA levels using real-time
      reverse transcription polymerase chain reaction, combined with terminal
      restriction fragment length polymorphism (T-RFLP) analysis, was applied to
      investigate the differential transcriptional responses among AOA species. High
      salinity levels repressed both archaeal and bacterial amoA mRNA expressions. On
      the other hand, high ammonium levels repressed only archaeal mRNA expression,
      suggesting that ammonium is a significant environmental factor shaping abundance
      of AOA and AOB. T-RFLP results indicated that the impacts of salinity and
      ammonium levels were different among AOA species. Although further study is
      necessary to add significance to our findings, the combination of the short-term
      mini-CSTR operations and amoA mRNA-based analyses allow a preliminary study on
      the influences of environmental factors on competition between the AOA and AOB
      communities.

PMID- 22643421
TI  - Recovery of calcium carbonate from steelmaking slag and utilization for acid mine
      drainage pre-treatment.
AB  - The conversion of steelmaking slag (a waste product of the steelmaking process)
      to calcium carbonate (CaCO(3)) was tested using hydrochloric acid, ammonium
      hydroxide and carbon dioxide via a pH-swing process. Batch reactors were used to
      assess the technical feasibility of calcium carbonate recovery and its use for
      pre-treatment of acid mine drainage (AMD) from coal mines. The effects of key
      process parameters, such as the amount of acid (HCl/calcium molar ratio), the pH
      and the CO(2) flow rate were considered. It was observed that calcium extraction
      from steelmaking slag significantly increased with an increase in the amount of
      hydrochloric acid. The CO(2) flow rate also had a positive effect on the
      carbonation reaction rate but did not affect the morphology of the calcium
      carbonate produced for values less than 2 L/min. The CaCO(3) recovered from the
      bench scale batch reactor demonstrated effective neutralization ability during
      AMD pre-treatment compared with the commercial laboratory grade CaCO(3).

PMID- 22643422
TI  - Micropollutants removal in an anaerobic membrane bioreactor and in an aerobic
      conventional treatment plant.
AB  - The paper expresses an attempt to tackle the problem due to the presence of
      micropollutants in wastewater which may be able to disrupt the endocrine system
      of some organisms. These kinds of compounds are ubiquitously present in municipal
      wastewater treatment plant (WWTP) effluents. The aim of this paper is to compare
      the fate of the alkylphenols-APs (4-(tert-octyl)) phenol, t-nonylphenol and 4-p
      nonylphenol and the hormones (estrone, 17beta-estradiol and 17alpha
      ethinylestradiol) in a submerged anaerobic membrane bioreactor (SAMBR) pilot
      plant and in a conventional activated sludge wastewater treatment plant (CTP).
      The obtained results are also compared with the results obtained in a previous
      study carried out in an aerobic MBR pilot plant. The results showed that the APs
      soluble concentrations in the SAMBR effluent were always significantly higher
      than the CTP ones. Moreover, the analyses of the suspended fraction revealed that
      the AP concentrations in the SAMBR reactor were usually higher than in the CTP
      reactor, indicating that under anaerobic conditions the APs were accumulated in
      the digested sludge. The aerobic conditions maintained both in the CTP system and
      in the aerobic MBR favoured the APs and hormones degradation, and gave rise to
      lower concentrations in the effluent and in the reactor of these systems.
      Furthermore, the results also indicated that the degradation of APs under aerobic
      conditions was enhanced working at high solid retention time (SRT) and hydraulic
      retention time (HRT) values.

PMID- 22643423
TI  - Anaerobic waste activated sludge co-digestion with olive mill wastewater.
AB  - Co-digestion of waste activated sludge (WAS) with agro-industrial organic
      wastewaters is a technology that is increasingly being applied in order to
      produce increased gas yield from the biomass. In this study, the effect of olive
      mill wastewater (OMW) on the performance of a cascade of two anaerobic continuous
      stirred tank (CSTR) reactors treating thickened WAS at mesophilic conditions was
      investigated. The objectives of this work were (a) to evaluate the use of OMW as
      a co-substrate to improve biogas production, (b) to determine the optimum
      hydraulic retention time that provides an optimised biodegradation rate or
      methane production, and (c) to study the system stability after OMW addition in
      sewage sludge. The biogas production rate at steady state conditions reached
      0.73, 0.63, 0.56 and 0.46 l(biogas)/l(reactor)/d for hydraulic retention times
      (HRTs) of 12.3, 14, 16.4 and 19.7 d. The average removal of soluble chemical
      oxygen demand (sCOD) ranged between 64 and 72% for organic loading rates between
      0.49 and 0.75 g sCOD/l/d. Reduction in the volatile suspended solids ranged
      between 27 and 30%. In terms of biogas selectivity, values of 0.6 l(biogas)/g
      tCOD removed and 1.1 l(biogas)/g TVS removed were measured.

PMID- 22643424
TI  - Synergetic degradation of Fe/Cu/C for groundwater polluted by trichloroethylene.
AB  - This study investigated the enhancement of synergetic degradation of Fe/Cu/C (Fe:
      commercial iron, Cu: solid product of Fe reacted with CuSO(4), C: carbon powder)
      for simulated groundwater contaminated by trichloroethylene (TCE). Zero valent
      iron (ZVI) as a reducing agent was proved to be effective for TCE removal. The
      Fe/Cu/C system resulted in higher reduction efficiency as a result of the
      synergetic role of Fe/Cu and Fe/C microelectrode than the Fe (ZVI) or Fe/Cu
      system, and the half-life was only about 0.4 h. When m(Fe) achieved 12.5 g L(-1),
      the residual concentration of TCE almost leveled off. Fe:Cu = 10:1 or m(C) =
      0.0086 g can induce the optimum function for TCE degradation. A neutral condition
      was appropriate for TCE degradation, and an acidic system slightly favored TCE
      dechlorination compared with an alkaline system. GC/MS analysis indicated that
      TCE was dechlorinated to 1,1-dichloroethene (1,1-DCE), cis-1,2-dichloroethene
      (cis-DCE) and vinyl chloride (VC), and 1,1-DCE might be the precursor. Fe/Cu/C
      reduction is a highly promising technique for TCE removal, and it is an excellent
      alternative to enhance TCE reductive dechlorination.

PMID- 22643425
TI  - Water quality as an indicator of hydrogeological conditions: a case study of the
      Belgrade Groundwater Source (Sava/Danube confluence area).
AB  - The City of Belgrade receives most of its drinking water supply from the alluvial
      aquifer of the Sava River. The wells are radial, placed in the lower part of the
      aquifer, so they partly run below the Sava riverbed. However, the groundwater
      quality of the wells in one part of the source (near the confluence of the Sava
      and Danube rivers) is found to differ somewhat from the groundwater quality of
      the other wells. The finding gave rise to additional investigations. The results
      revealed the existence of a deeper, limestone aquifer which is isolated from
      upper alluvial sediments by a thick layer of clay in most of the terrain. The
      naturally potential hydraulic contact of the two aquifers was additionally
      maintained by well operation in this part of the source. According to multiple
      analyses of groundwater flow using a hydrodynamic mathematical model, a
      hydrogeological and hydraulic system of groundwater flow was defined. Although
      the wells are situated adjacent to the river, and some well laterals are below
      the riverbed, most of the groundwater that flows to the wells is partly from the
      wider zone of the alluvial aquifer, and partly from the deeper aquifer. The
      initial results of hydrochemical investigations also showed an unexpected,
      inverse oxic character of the groundwater in these two aquifers.

PMID- 22643426
TI  - Equipping metallo-supramolecular macrocycles with functional groups: assemblies
      of pyridine-substituted urea ligands.
AB  - A series of di-(m-pyridyl)-urea ligands were prepared and characterized with
      respect to their conformations by NOESY experiments and crystallography. Methyl
      substitution in different positions of the pyridine rings provides control over
      the position of the pyridine N atoms relative to the urea carbonyl group. The
      ligands were used to self-assemble metallo-supramolecular M(2)L(2) and M(3)L(3)
      macrocycles which are generated in a finely balanced equilibrium in DMSO and DMF
      according to DOSY NMR experiments and ESI FTICR mass spectrometry. Again,
      crystallography was used to characterize the assemblies. Methyl substitution in
      positions next to the pyridine nitrogen prevents coordination, while the other
      ligands form small metallo-supramolecular macrocycles. The incorporated urea
      carbonyl groups provide hydrogen bonding sites which converge towards the center
      of the assemblies.

PMID- 22643440
TI  - Drugs for menopausal symptoms.

PMID- 22643441
TI  - Choice of drugs for heparin-induced thrombocytopenia.

PMID- 22643442
TI  - Cochlear implant device failure secondary to cholesterol granuloma-mediated
      cochlear erosion.
AB  - STUDY DESIGN: Case report. SETTING: A tertiary care pediatric hospital. PATIENT:
      A 7-year-old boy complained of retroauricular pain 3.5 years after cochlear
      implantation. Temporal bone computed tomographic scan revealed a soft tissue
      density filling the mastoid and middle ear space. There was extensive osseous
      erosion involving the cochlear promontory that resulted in lateral displacement
      electrode array into the middle ear space. INTERVENTION: Mastoidectomy with
      removal of cochlear implant. RESULTS: Pathologic examination of the soft tissue
      filling the mastoid cavity was consistent with a cholesterol granuloma. The
      cultures of the mastoid cavity demonstrated no growth. Examination of the
      explanted device revealed a cell layer covering the length of the electrode. The
      stylet tract was filled with cells that grew out through the silicone component.
      No birefringent cholesterol crystals were detected in the tissue surrounding the
      electrode. Biofilms were not identified. CONCLUSION: The authors describe a
      unique case of a cholesterol granuloma of the middle ear and mastoid in a
      cochlear implant recipient causing erosion of the otic capsule and displacement
      of the cochlear implant electrode array into the middle ear space.

PMID- 22643443
TI  - Neoangiogenesis in temporal bone carcinoma: the prognostic role of CD105.
AB  - OBJECTIVE: Temporal bone squamous cell carcinoma (SCC) accounts for less than 2%
      of all head and neck tumors. Its biologic parameters should be investigated
      because clinicopathologic factors are often inaccurate for the purposes of its
      prognosis. CD105 is a proliferation-associated protein expressed in angiogenic
      endothelial cells and a potential prognostic indicator for several solid
      malignancies. The present study is the first to investigate the prognostic role
      of CD105 expression in temporal bone SCC. STUDY DESIGN: Retrospective
      clinicopathologic investigation. SETTING: Tertiary referral centers. PATIENTS:
      Twenty consecutive operable patients with temporal bone SCC. INTERVENTION: CD105
      immunohistochemical expression in primary temporal bone SCCs was assessed using
      image analysis. MAIN OUTCOME MEASURES: CD105 expression was correlated with
      conventional clinicopathologic and prognostic parameters. RESULTS: Using the
      revised Pittsburgh staging system, T and stage correlated with local recurrence
      rate (p = 0.0001 and p = 0.0001, respectively) and disease-free survival (p =
      0.043 and p = 0.018, respectively). The recurrence rate was significantly higher
      (p = 0.038) and the disease-free survival shorter in patients with CD105
      expression of 9.44% or higher (p = 0.038) than in cases where it was less than
      9.44%. The crude carcinoma recurrence risk ratio of was 5.9 times higher for
      patients whose CD105 expression was 9.44% or higher. CONCLUSION: CD105 expression
      in activated endothelial cells of temporal bone SCC can be considered potentially
      useful for detecting patients at a higher risk of local disease recurrence after
      treatment. Further investigations are needed to ascertain the feasibility of
      incorporating targeted anti-CD105 therapy in multimodality or multitarget
      strategies for temporal bone SCC treatment.

PMID- 22643444
TI  - In vitro magnetic resonance imaging evaluation of ossicular implants at 3 T.
AB  - HYPOTHESIS: Ossicular implants made from metallic materials may be acceptable or
      pose hazards for patients referred for magnetic resonance imaging (MRI)
      examinations, depending on the outcome of proper MRI testing procedures.
      BACKGROUND: Using a 3-T MR system, 2 ossicular implants were tested for magnetic
      field interactions, heating, and artifacts. MATERIALS AND METHODS: Two different
      ossicular implants (Stainless Steel/Fluoroplastic Sanna-Type Piston [6 mm in
      length] and the Offset ALTO Total Prosthesis [15 mm in length,
      titanium/silicone]; Grace Medical, Memphis, TN, USA) were selected for testing,
      which represented the largest metallic mass and materials with the highest
      magnetic susceptibilities, with the intent of applying the MRI findings to other
      ossicular implants. The implants were evaluated at 3-T for magnetic field
      interactions, heating, and artifacts using standard previously described
      techniques. RESULTS: Each ossicular implant showed relatively minor magnetic
      field interactions that will not be associated with movement in situ. Heating was
      not excessive (highest temperature change, <= 1.6 degrees C; background
      temperature change, 1.5 degrees C). Artifacts, although relatively small, may
      create issues for diagnostic imaging if the area of interest is in the same area
      or close to these ossicular implants. CONCLUSION: The results of this
      investigation demonstrated that it would be acceptable (i.e., "MR conditional"
      using current terminology) for patients with these ossicular implants to undergo
      MRI examinations at 3 T or less. In consideration of the materials and dimensions
      of the implants that underwent testing, these findings pertain to many other
      similar ossicular implants from the same manufacturer.

PMID- 22643445
TI  - Is cartilage tympanoplasty more effective than fascia tympanoplasty? A systematic
      review.
AB  - OBJECTIVE: A systematic review to compare the effectiveness of the use of
      cartilage (with or without perichondrium) with temporalis fascia used in
      tympanoplasty. DATA SOURCE: The following databases were searched for relevant
      studies: MEDLINE, Embase, CINAHL, the Cochrane Library including the Cochrane
      Central Register of Controlled Trials, Google scholar, and the PubMed. There was
      no restriction as to the design or date of publication. STUDY SELECTIONS: We
      selected randomized controlled trials (RCTs) and retrospective studies comparing
      cartilage and temporalis fascia tympanoplasty in relation to 2 outcomes:
      morphological and functional success. Initial search identified 2,091
      publications. All titles and abstracts were reviewed by 2 of the authors, and 103
      relevant articles were studied. However, only 14 studies met the inclusion
      criteria for this review. These included 3 RCTs, 10 retrospective studies, and 1
      literature review. RESULTS: Three level 1 (RCTs) and 11 level 3 and 4 evidence
      based studies were included (n = 1,475 patients). One RCT and 3 retrospective
      studies showed a statistically significant better morphological success, that is,
      intact ear drum with cartilage graft with or without perichondrium. There was,
      however, no statistically significant difference between cartilage and temporalis
      fascia tympanoplasty regarding function, namely, hearing outcome. The need for
      revision rates was approximately 10% with cartilage and 19% with fascia
      tympanoplasty. CONCLUSION: Tympanoplasty using cartilage with or without
      perichondrium has better morphological outcome than tympanoplasty using
      temporalis fascia. However, there was no statistically significant difference in
      hearing outcomes between the 2 grafts.

PMID- 22643446
TI  - Stability of osseointegrated bone conduction systems in children:  a pilot study.
AB  - OBJECTIVES: To obtain objective data of bone conduction implant stability and
      osseointegration in children; to compare in pediatric subjects the stability and
      osseointegration of the novel TiOblast-coated implant system (BI300) to the
      previous generation, as-machined model. STUDY DESIGN: Multicenter, controlled,
      nonrandomized, longitudinal, prospective study. SETTING: Tertiary referral
      center. LEVEL OF EVIDENCE: IIIb PATIENTS: Ten subjects were enrolled, aged
      younger than 16 years and without comorbidities that negatively affect
      osseointegration. All patients were implanted "single stage": 5 received the
      previous generation, pure titanium fixture (control group), and 5 were implanted
      the BI300, TiOblast-coated fixture (test group). INTERVENTIONS: Measurement of
      implant stability and osseointegration. MAIN OUTCOME MEASURE(S): Implant
      stability and osseointegration as measured by means of resonance frequency
      analysis intraoperatively, at 1 week, 2 weeks, 1 month, and every month till
      processor loading 6 months after surgery. RESULTS: BI300 is, on average, more
      stable than the control fixture, both intraoperatively and over time till
      processor loading. Over the 6 months' follow-up, a stability increase was
      observed with both models, although it resulted statistically not significant.
      CONCLUSION: The BI300 implant system has a greater primary stability as compared
      with the previous generation model, but its faster osseointegration could not be
      definitely verified. It is reasonable to assume that the BI300 fixture will
      enable surgeons to perform single-stage surgery more safely and with a lower
      failure rate. The possibility of an earlier processor loading remains to be
      confirmed in a greater sample.

PMID- 22643447
TI  - Artificial horizon effects on motion sickness and performance.
AB  - HYPOTHESIS: To investigate whether the projection of Earth-referenced scenes
      during provocative motion can alleviate motion sickness severity and prevent
      motion sickness-induced degradation of performance. BACKGROUND: Exposure to
      unfamiliar motion patterns commonly results in motion sickness and decreased
      performance. METHODS: Thirty subjects with moderate-to-severe motion sickness
      susceptibility were exposed to the recorded motion profile of a missile boat
      under moderate sea conditions in a 3-degrees-of-freedom ship motion simulator.
      During a 120-minute simulated voyage, the study participants were repeatedly put
      through a performance test battery and completed a motion sickness susceptibility
      questionnaire, while self-referenced and Earth-referenced visual scenes were
      projected inside the closed simulator cabin. RESULTS: A significant decrease was
      found in the maximal motion sickness severity score, from 9.83 +/- 9.77 (mean +/-
      standard deviation) to 7.23 +/- 7.14 (p < 0.03), when the visual display better
      approximated the full scale of the roll, pitch, and heave movements of the
      simulator. Although there was a significant decrease in sickness severity,
      substantial symptoms still persisted. Decision making, vision, concentration,
      memory, simple reasoning, and psychomotor skills all deteriorated under the
      motion conditions. However, no significant differences between the projection
      conditions could be found in the scores of any of the performance tests.
      CONCLUSION: Visual information regarding the vessel's movement provided by an
      artificial horizon device might decrease motion sickness symptoms. However,
      although this device might be suitable for passive transportation, the continued
      deterioration in performance measures indicates that it provides no significant
      advantage for personnel engaged in the active operation of modern vessels.

PMID- 22643454
TI  - A non-fused mono-meso-free pentaphyrin and its rhodium(I) complex.
AB  - 5,10,15,20-Tetrakis(pentafluorophenyl) [22]pentaphyrin(1.1.1.1.1) 7 was
      synthesised and its bis-rhodium(I) complex 12 has been revealed to be a non
      fused, yet planar pentaphyrin with an inverted pyrrole. Both 7 and 12 are
      aromatic, showing sharp Soret-like bands and diatropic ring currents.

PMID- 22643456
TI  - Total-to-ionized calcium ratio predicts mortality in continuous renal replacement
      therapy with citrate anticoagulation in critically ill patients.
AB  - INTRODUCTION: Regional citrate anticoagulation is safe, feasible and increasingly
      used in critically ill patients on continuous renal replacement therapy (CRRT).
      However, in patients with hepatic or multi-organ dysfunction, citrate
      accumulation may lead to an imbalance of calcium homeostasis. The study aimed at
      evaluating the incidence and prognostic relevance of an increased total to
      ionized calcium ratio (T/I Ca(2+) ratio) and its association to hepatic
      dysfunction. METHODS: We performed a prospective observational study on n = 208
      critically ill patients with acute kidney injury (AKI) and necessity for CRRT
      with regional citrate anticoagulation (CRRT-citrate) between September 2009 and
      September 2011. Critical illness was estimated by Simplified Acute Physiology
      Score II; hepatic function was measured with indocyanine green plasma
      disappearance rate. After achieving a steady state of calcium homeostasis
      patients were classified into tertiles according to the T/I Ca(2+) ratio (<2.0
      versus 2.0 - 2.39 versus >= 2.4). RESULTS: The T/I Ca(2+) ratio was determined as
      an independent predictor for 28-day mortality in critically ill patients with AKI
      on CRRT-citrate confirmed by receiver operating characteristics and multivariate
      analysis (Area under the curve 0.94 +/- 0.02; p<0.001). A T/I Ca(2+) ratio >= 2.4
      independently predicted a 33.5-fold (p<0.001) increase in 28-day mortality-rate.
      There was a significant correlation between the T/I Ca(2+) ratio and the hepatic
      clearance (p<0.001) and the severity of critical illness (p<0.001). The efficacy
      and safety of citrate anticoagulation, determined by blood urea nitrogen, mean
      filter patency and bleeding episodes, were not significantly different between
      the tertiles. CONCLUSIONS: In patients on CRRT-citrate T/I Ca(2+) ratio is
      closely related to the clinical outcome and emerged as an independent predictor
      of 28-day mortality. Larger studies are required to define the cut-off and
      predictive value for the T/I Ca(2+) ratio. This ratio is associated with hepatic
      and/or multi-organ dysfunction and therefore an important therapeutic target.

PMID- 22643457
TI  - Multiphase enantioselective Kharasch-Sosnovsky allylic oxidation based on
      neoteric solvents and copper complexes of ditopic ligands.
AB  - Recoverable multiphase enantioselective catalytic systems for the Kharasch
      Sosnovsky oxidation of cycloalkenes with tert-butyl peroxybenzoate are described,
      based on the use of [BMIM][PF(6)] and a new solvent derived from glycerol as the
      catalyst reservoir phases, and chiral copper complexes with different ligands
      from the bis(oxazoline) family. The best results are obtained with the glycerol
      derived solvent and a recently described azabisoxazoline-based ditopic ligand,
      allowing up to four uses of the catalytic phase with good results.

PMID- 22643458
TI  - The forgotten minorities: health disparities of the lesbian, gay, bisexual, and
      transgendered communities.

PMID- 22643459
TI  - Firearms, youth homicide, and public health.
AB  - Homicide is seven times as common among U.S. non-Hispanic Black as among non
      Hispanic White youth ages 15 to 24 years. In 83% of these youth homicides, the
      murder weapon is a firearm. Yet, for more than a decade, the national public
      health position on youth violence has been largely silent about the role of
      firearms, and tools used by public health professionals to reduce harm from other
      potential hazards have been unusable where guns are concerned. This deprives
      already underserved populations from the full benefits public health agencies
      might be able to deliver. In part, political prohibitions against research about
      direct measures of firearm control and the absence of valid public health
      surveillance are responsible. More refined epidemiologic theories as well as
      traditional public health methods are needed if the U.S. aims to reduce disparate
      Black-White youth homicide rates.

PMID- 22643460
TI  - Extending Medicare immunosuppressive medication coverage.
AB  - African Americans and the poor are at a high risk of suffering from kidney
      disease and are at an extreme disadvantage when it comes to obtaining the
      resources needed to maintain a functioning kidney post-transplant. Medicare
      currently covers 80% of the cost of immunosuppressive therapy for up to three
      years following a Medicare-covered transplant for patients whose Medicare
      entitlement was based solely on their end-stage renal disease diagnosis. Adequate
      insurance coverage has the potential to prevent graft failure and
      retransplantation resulting from cost-related immunosuppressive medication
      nonadherence. Given the multifactorial nature of medication nonadherence,
      extending insurance coverage in an attempt to reduce graft failures should be
      coupled with intensive interventions to prevent the socioeconomic and various
      other factors associated with medication nonadherence. Lifetime Medicare coverage
      for all kidney-transplant recipients, coupled with medication adherence
      promotion, has the potential to minimize poor outcomes associated with graft
      failure, especially among minorities and the impoverished.

PMID- 22643461
TI  - What influences African American end-of-life preferences?
AB  - BACKGROUND: The U.S. population is aging and increasingly culturally diverse. The
      challenges of an aging population desiring a good end to their lives combined
      with soaring costs for medical care serve as a mandate for providers to be aware
      of both patient preferences and other factors influencing decision-making at the
      end of life. METHODS: Systematic review of published research studies examining
      African American preferences related to end-of-life care and decision-making.
      FINDINGS: There are well documented differences in preferences for end-of-life
      care and utilization of services between non-Hispanic Whites and African
      Americans. African Americans do not use advance care planning (ACP) documents or
      hospice to the same extent as non-Hispanic Whites, and, even after controlling
      for income and access, the difference is significant. Many African Americans
      choose aggressive life-sustaining treatment at the end of life, even if that
      treatment seems likely to confer great burden with little chance of benefit. The
      reasons for this are multi-faceted and include knowledge of and access to
      services, historical mistrust of the health care system, and spiritual beliefs.
      CONCLUSIONS: African American end-of-life choices are influenced by knowledge of
      and access to services as well as by shared cultural beliefs in the role of
      family and others in decision-making, mistrust toward the health care system, and
      the importance of spirituality.

PMID- 22643448
TI  - Have studies of the developmental regulation of behavioral phenotypes revealed
      the mechanisms of gene-environment interactions?
AB  - This review addresses the recent convergence of our long-standing knowledge of
      the regulation of behavioral phenotypes by developmental experience with recent
      advances in our understanding of mechanisms regulating gene expression. This
      review supports a particular perspective on the developmental regulation of
      behavioral phenotypes: That the role of common developmental experiences (e.g.
      maternal interactions, peer interactions, exposure to a complex environment,
      etc.) is to fit individuals to the circumstances of their lives within bounds
      determined by long-standing (evolutionary) mechanisms that have shaped responses
      to critical and fundamental types of experience via those aspects of gene
      structure that regulate gene expression. The phenotype of a given species is not
      absolute for a given genotype but rather variable within bounds that is
      determined by mechanisms regulated by experience (e.g. epigenetic mechanisms).
      This phenotypic variation is not necessarily random, or evenly distributed along
      a continuum of description or measurement, but often highly disjointed, producing
      distinct, even opposing, phenotypes. The potentiality for these varying
      phenotypes is itself the product of evolution, the potential for alternative
      phenotypes itself conveying evolutionary advantage. Examples of such phenotypic
      variation, resulting from environmental or experiential influences, have a long
      history of study in neurobiology, and a number of these will be discussed in this
      review: neurodevelopmental experiences that produce phenotypic variation in
      visual perception, cognitive function, and emotional behavior. Although other
      examples will be discussed, particular emphasis will be made on the role of
      social behavior on neurodevelopment and phenotypic determination. It will be
      argued that an important purpose of some aspects of social behavior is regulation
      of neurobehavioral phenotypes by experience via genetic regulatory mechanisms.

PMID- 22643463
TI  - Developing multilingual prescription instructions for patients with limited
      english proficiency.
AB  - This article describes the development of a set of patient-centered prescription
      medication instructions and their translation into Chinese, Korean, Russian,
      Spanish, and Vietnamese. Challenges and lessons learned from this process are
      reported to inform future efforts to develop easy-to-understand, multilingual
      materials for use in health care settings.

PMID- 22643464
TI  - Trust in primary care providers and antiretroviral adherence in an urban HIV
      clinic.
AB  - Interpersonal trust is an integral component of the patient-provider relationship
      and has been associated with patient adherence to medications. Studies suggest
      African Americans may have lower levels of trust in their health care providers
      than non-Hispanic Whites. This study examines the association between trust in
      one's primary care provider (PCP) and antiretroviral (ARV) adherence among 175
      patients at an urban HIV clinic. Interviews elicited participants' level of trust
      in their current PCP using a multiple-item trust scale and assessed ARV adherence
      with a seven-day recall questionnaire. Logistic regression was used to ascertain
      the effect of trust in PCP on ARV adherence. High trust in PCP was significantly
      associated with increased odds of ARV adherence compared with low trust (adjusted
      odds ratio, 2.67; 95% confidence interval, 1.24 to 5.76; p=.01). Enhancing trust
      in PCPs may be a good target for interventions to improve ARV adherence,
      particularly among African American patients.

PMID- 22643462
TI  - Physical activity interventions with healthy minority adults: meta-analysis of
      behavior and health outcomes.
AB  - This meta-analysis is a systematic compilation of research focusing on various
      exercise interventions and their impact on the health and behavior outcomes of
      healthy African American, Hispanic, Native American, and Native Hawaiian adults.
      Comprehensive searching located published and unpublished studies. Random-effects
      analyses synthesized data to calculate effect sizes (ES) as a standardized mean
      difference (d) and variability measures. Data were synthesized across 21,151
      subjects in 100 eligible samples. Supervised exercise significantly improved
      fitness (ES=.571-.584). Interventions designed to motivate minority adults to
      increase physical activity changed subsequent physical activity behavior (ES=.172
      .312) and anthropometric outcomes (ES=.070-.124). Some ES should be interpreted
      in the context of limited statistical power and heterogeneity. Attempts to match
      intervention content and delivery with minority populations were inconsistently
      reported. Healthy minority adults experienced health improvements following
      supervised exercise. Interventions designed to motivate subjects to increase
      physical activity have limited magnitude heterogeneous effects.

PMID- 22643465
TI  - Promoting brain health for African Americans: evaluating the healthy brain
      initiative, a community-level demonstration project.
AB  - INTRODUCTION: African Americans are at significantly greater risk than non
      Hispanic Whites or Hispanics for cognitive impairment. This study presents an
      evaluation of the Alzheimer's Association's Healthy Brain Initiative, a
      culturally tailored community-level intervention to increase knowledge and
      awareness of brain health among African American baby boomers. METHODS: The
      evaluation used a mixed-method design with data collection before, during, and
      after intervention implementation. RESULTS: The intervention was implemented with
      fidelity to model design by Alzheimer's Association chapters. Partnerships
      between chapters and community organizations to increase awareness of brain
      health among African American baby boomers were facilitated. Community members
      who participated in intervention workshops demonstrated increased knowledge,
      awareness, and intentions to engage in recommended health-protective behaviors.
      CONCLUSION: A community-level intervention can increase knowledge and awareness
      of brain health among African American baby boomers. In addition, such
      interventions can motivate participants' intentions to engage in health
      protective behaviors to maintain overall health and brain health.

PMID- 22643466
TI  - Type and frequency of substances injected in a sample of Haitian immigrant
      picuristes (informal injectionists) and clients.
AB  - In view of health inequities disfavoring Haitians, substances given by Florida
      Haitian picuristes/informal injectionists were investigated. Semi-structured
      interviews of 10 picuristes and 25 clients were obtained, transcribed, and
      analyzed using ATLAS.ti and SPSS. The most commonly injected substances were
      antibiotics (reported by eight of 10 picuristes, who sometimes compose substances
      when conventional pharmaceuticals are inaccessible). Haitian picuristes give
      injections based on clients' reported symptoms, and no clear or consistent
      protocol appears to exist for diagnosis, insuring injection safety, determining
      amount, or frequency of substances injected. Findings indicate frequent use and
      misuse of antibiotics. While not limited to this sample of Haitian immigrants,
      frequent and unmonitored use of antibiotics may add to health disparities by
      increasing antibiotic resistance among them and among others with similar health
      practices. A harm reduction approach for mitigating effects of antibiotic overuse
      is suggested.

PMID- 22643468
TI  - Pay-for-performance programs to reduce racial/ethnic disparities: what might
      different designs achieve?
AB  - Pay-for-performance (P4P) programs may have unintended effects on racial/ethnic
      disparities. We used patient-level quality scores from the Hospital Quality
      Alliance and ranked hospitals by overall quality and by racial/ethnic
      disparities. We then modeled the effects of different P4P designs on national
      disparity scores. The models using overall quality to rank hospitals resulted in
      modest reductions in national disparity scores, although these were smaller than
      the reductions that were found from programs using disparities to rank hospitals.
      These results suggest that many hospitals treat Whites and minorities equitably.
      Nevertheless, in order to maximize both improvements in quality and reductions in
      national disparities, P4P programs should consider an approach that considers
      both overall quality and reductions in disparities when setting incentives.

PMID- 22643467
TI  - "I live by shooting hill"-a qualitative exploration of conflict and violence
      among urban youth in New Haven, Connecticut.
AB  - To elucidate urban youths' perceptions of conflict and violence we conducted a
      qualitative study among minority urban youths in New Haven, Connecticut. We
      utilized the ecological framework to explore the multilevel nature of the
      findings, and triangulated results with a parallel quantitative study. We found
      risk factors for violence at multiple levels including lack of interpersonal
      anger management skills (individual level); parents not physically present in the
      household (relationship level); residence in crime and gang-ridden neighborhoods
      (community level); and socioeconomic inequalities between neighborhoods, as
      reflected by participants' perception of the inadequacy of neighborhood resources
      to provide safety (societal level). Neighborhood resources were perceived as
      sparse, and police were not regarded as a protective factor (sometimes rather as
      racially discriminatory). Participants' statements pertaining to feelings of
      isolation, racism, and violence without strong parental, neighborhood, and school
      support may impede prosocial attitudes and behaviors throughout adolescence and
      young adulthood.

PMID- 22643469
TI  - Self-management of type 2 diabetes among African Americans in the Arkansas Delta:
      a strengths perspective in social-cultural context.
AB  - This qualitative study explored underlying factors influencing the promotion of
      type 2 diabetes (T2D) self-management among adult African Americans diagnosed
      with T2D in the Arkansas Delta. Our narrative approach gathered insights in the
      participants' own voices and placed their T2D self-management experiences in
      social-cultural-historical contexts. Using purposive sampling, 31 participants
      (16 women and 15 men) were selected and interviewed. The participants showed low
      awareness of T2D's chronic nature because of its asymptomatic or nonspecific
      symptoms. They interpreted medically prescribed dietary and physical exercise
      guidelines as impractical and culturally irrelevant for them. Medication non
      adherence was due to inadequate knowledge and awareness of T2D as a chronic
      disease, and suspicion and mistrust of the formal medical system. To develop
      culturally-targeted interventions to advance self-management outcomes, we must
      understand from and with African Americans the strengths of social-cultural
      contexts in which they live and make their health behavior choices. Engaging
      African Americans diagnosed with T2D in community-based programs may be a
      promising approach.

PMID- 22643470
TI  - Disparities in HIV-treatment responses between Haitians, African Americans, and
      Hispanics living in Miami-Dade County, Florida.
AB  - BACKGROUND: Studies evaluating response to treatment with Highly Active
      Antiretroviral Therapy (HAART) fail to examine Haitian patients living in the
      U.S. as a distinct group. METHODS: This study was designed to determine the
      effectiveness of HAART in Haitians compared with other minority groups. We
      conducted a retrospective cohort study of HIV patients from two clinics. The
      cohort included 96 Hispanics, 60 African Americans, and 49 Haitians, after
      reviewing a total of 891 charts. RESULTS: At 96 weeks, fewer Haitians (58.5%)
      achieved a suppressed viral load than African American (74.1%) or Hispanic
      (82.8%) patients (p=.021). Median CD4 counts at baseline were lowest among
      Haitians, with 158 cells/mm3, compared with African Americans, 176 cells/mm3 and
      Hispanics, 199 cells/mm3. CONCLUSIONS: Haitians are not doing as well on HAART as
      other groups. This may be explained by linguistic, cultural, or other barriers
      that are not currently addressed by the health care system in the United States.

PMID- 22643471
TI  - Condom use among HIV-positive sexually active adults and partner's HIV status in
      Dar es Salaam, Tanzania.
AB  - Consistent and proper use of condoms has been found to be effective in preventing
      HIV transmission and other sexually transmitted diseases. We examined the
      predictors of condom use and knowledge of partner's HIV status among 731 HIV
      positive individuals who had sex in the past six months. Data are from an
      incoming service form administered to clients who visited the Muhimbili
      University College of Health Sciences' Voluntary Counseling and Testing (VCT)
      site in Dar es Salaam, Tanzania between 1997-2008 (N=45,071). Sixteen percent
      reported always using a condom in the past six months. Multivariate logistic
      regression revealed that age, and knowledge of partner's HIV status were the
      strongest predictors of consistent condom use. The risk of future HIV infections
      in this region remains high. Future efforts to prevent new HIV infections should
      aim to increase condom use, and prevention practices that facilitate HIV-positive
      individuals to communicate their HIV status with partners.

PMID- 22643472
TI  - Degrees of difference among minority female juvenile offenders' psychological
      functioning, risk behavior engagement, and health status: a latent profile
      investigation.
AB  - Given the increase in the number of female youth who come in contact with the
      juvenile justice system, particularly those from ethnic minority backgrounds,
      concerns have been raised about the health status of this population. Using a
      latent profile analysis, we identified health profiles using indicators of
      psychological well-being, health risk behaviors, and health status. Participants
      included 153 minority adolescent females (M=15.13, SD=1.70) who were currently in
      a juvenile diversion program. Results indicated that a three-class solution fit
      the data optimally. Profiles included girls with low to moderate health risks
      (n=35; 22.9%), higher mental health symptoms (n=68; 44.4%), and a combination of
      multiple health risks (n=50; 32.7%). Additionally, demographic, contextual and
      offense-related variation existed across health profiles. Treatment and policy
      implications are discussed.

PMID- 22643474
TI  - Health literacy of an urban business community.
AB  - The impact of community-based organizations on the delivery of health care
      knowledge is well documented. Little research has focused on the importance of
      health literacy in the dissemination of health care information by minority small
      business owners. This study sampled 38 business owners within a local business
      district to assess their level of health literacy. Although adequate health
      literacy is not required to serve as a community resource, it may be necessary to
      understand the health literacy level of local business owners as gatekeepers in
      order to develop appropriate training/educational programs. The results of this
      descriptive cross-sectional study indicate that for sample of business owners,
      health literacy levels are adequate. The findings suggest the feasibility of
      using local business owners as disseminators of health-related materials to the
      communities in which they operate their businesses.

PMID- 22643473
TI  - Depressive symptoms, substance abuse, and intimate partner violence among
      pregnant women of diverse ethnicities.
AB  - This study examines the relationship between self-reported depressive symptoms,
      substance abuse and intimate partner violence among 602 African American,
      Hispanic, White, Asian American, American Indian/Alaskan Native, Native
      Hawaiian/Pacific Islander pregnant women who are clients of the Augusta
      Partnership for Children, Inc., a nonprofit collaborative that works with
      agencies, organizations, and individuals to improve the lives of children and
      families in Augusta-Richmond County, Georgia. Descriptive statistics and
      significant relationships among selected variables using correlation and
      regression analyses were conducted. Findings are intended to inform strategies
      for community-based programs better to assist women of diverse ethnicities with
      addressing depression, substance abuse, and intimate partner violence during
      their pregnancies, with the ultimate aim of improving health and mental health
      outcomes for women and children.

PMID- 22643475
TI  - Disease prevalence and use of health care among a national sample of black and
      white male state prisoners.
AB  - U.S. prisons have a court-affirmed mandate to provide health care to prisoners.
      Given this mandate, we sought to determine whether use of prison health care was
      equitable across race using a nationally-representative sample of Black and White
      male state prisoners. We first examined the prevalence of health conditions by
      race. Then, across all health conditions and for each of 15 conditions, we
      compared the proportion of Black and White male prisoners with the condition who
      received health care. For most conditions including cancer, heart disease, and
      liver-related disorders, the age-adjusted prevalence of disease among Blacks was
      lower than among Whites (p<.05). Blacks were also modestly more likely than
      Whites to use health care for existing conditions (p<.05), particularly
      hypertension, cerebral vascular accident/brain injury, cirrhosis, flu-like
      illness, and injury. The observed racial disparities in health and health care
      use are different from those among non-incarcerated populations.

PMID- 22643476
TI  - Racial and ethnic variation in ADHD, comorbid illnesses, and parental strain.
AB  - Our objective was to understand the racial and ethnic variation in parental
      strain for non-Latino White, African American, and Latino parents of children
      with ADHD and other comorbid diagnoses. We selected 5,397 children with a current
      diagnosis of ADHD from the 2007 National Survey of Child Health (NSCH) and
      identified comorbid conditions that could cause additional parental strain.
      Multivariate regression analyses of parental strain, from ADHD plus comorbid
      physical and mental health conditions, varied by race and ethnicity in our
      sample. Additionally we found variables such as mother's mental health, family
      structure and social support to play significant roles in parental strain. These
      findings indicate a need for greater understanding of the family mechanisms in
      place that affect parental strain for these varying populations of families.
      Interventions to reduce parental strain also need to be tailored to the specific
      needs of racially and ethnically diverse parents of children with ADHD.

PMID- 22643477
TI  - African American parents' HPV vaccination intent and concerns.
AB  - This study describes attitudes and social and environmental factors that affect
      African American parents' intent to vaccinate their daughters against human
      papillomavirus (HPV). Thirty African American parents of daughters aged nine to
      17 years and no history of HPV infection completed semi-structured interviews.
      Interviews addressed factors that influenced intent to vaccinate, perception of
      community norms related to vaccination, vaccination scenarios involving place of
      vaccination, and vaccination prior to or after the child's initiation of sexual
      activity. A recurring theme was the influence of physician recommendation on
      African American parents' intent to obtain HPV vaccination for their daughters.
      Most parents reported that they could overcome barriers to vaccination, except
      vaccine costs and lack of insurance. While religious beliefs were important to
      parents, they reported that they would not interfere with vaccination decisions;
      fears of early sexuality due to vaccination were limited. The implications of
      these findings are discussed.

PMID- 22643478
TI  - Prenatal care, childhood obesity, and ethnic health disparities: analyses from a
      unique population database.
AB  - This paper explores the association between prenatal care and childhood obesity
      across racial/ethnic groups, with special focus on Asians, Native Hawaiian and
      other Pacific Islanders (NHOPI), and non-Hispanic Whites. Data were drawn from a
      statewide population-based data source that linked vital and administrative
      records for a large cohort of children (n=227,032). Multivariate logistic
      regression was used to estimate odds of overweight and obesity among children
      whose mothers received first trimester prenatal care versus those who did not.
      Compared with White and Asian women, NHOPI women had later initiation of prenatal
      care. However, NHOPI women who initiated early prenatal care had children with
      significantly lower risks of obesity and overweight than their counterparts who
      delayed such care. Timely prenatal care may be associated, with lower childhood
      obesity through focused monitoring and counseling on pregnancy-related weight
      gain as well as through reducing other potentially deleterious prenatal behaviors
      for this high-risk and underserved population.

PMID- 22643479
TI  - An end to chronic homelessness: an introduction to the 100,000 homes campaign.
AB  - Across the nation communities are rapidly identifying and housing their most
      vulnerable people experiencing homelessness. Building on these examples,
      Community Solutions and the Institute for Healthcare Improvement have launched
      the 100,000 Homes Campaign, an historic effort to eliminate chronic homelessness
      by July 2014.

PMID- 22643480
TI  - The costs and adequacy of safety net access for the uninsured in Genesee County,
      Michigan.
AB  - This commentary examines Genesee County (Flint) Michigan to explore whether a
      well-structured safety net system is able to provide low-income uninsured people
      adequate access to care at a reasonable cost. Genessee County is one of the more
      economically challenged communities in the country. This commentary explores the
      cost and adequacy of safety net care in Genessee County under the Genessee Health
      Plan (GHP). The analysis compares the cost of services under GHP to the cost of
      the same services offered by local private insurers and Medicaid. An analysis
      found that GHP, Flint-area physicians, hospitals, and foundations have succeeded
      in providing basic medical care access to a substantial majority of their low
      income uninsured citizens. The costs of care, both paid by GHP and donated by
      local providers, are substantially less than the estimated costs if this
      population were covered by full Medicaid or private insurance.

PMID- 22643481
TI  - A model plan for the uninsured: delivering quality and affordability in a limited
      benefit managed care safety net program in Flint, Michigan.
AB  - This paper presents the background and multiyear outcome data for a limited
      benefit safety-net care program in Michigan. It is a possible solution for
      policymakers and hospital/clinic administrators to consider when evaluating plans
      to provide primary care for the 30 million uninsured Americans who will be
      affected by the Affordable Care Act.

PMID- 22643482
TI  - Using theater arts to engage Latino families in dialogue about adolescent sexual
      health: the PATH -AT program.
AB  - This paper describes the Promoting Alternatives for Teen Health through Artes
      Teatro (PATH-AT) program, a peer-led, after-school, abstinence-based education
      intervention, targeting Latino/a youth at risk for teenage pregnancy and their
      parents. A distinguishing trait of the program is the use of theater arts to
      engage program participants with program content.

PMID- 22643483
TI  - Federally qualified health center patients and generic drug discount programs.
AB  - This study evaluates the factors associated with utilization of generic drug
      discount program (GDDP) among federally qualified health center (FQHC) patients
      in Houston, Texas. A survey to determine awareness and use of GDDP was
      administered to 304 patients at three FQHCs in Houston, Texas. Patients at FQHCs
      treated with courtesy by pharmacy staff (OR: 14.1, 95% CI: 7.9-25.2), patients
      with a perception of positive impact of GDDP on their health (OR: 7.6, 95% CI:
      4.5-12.7), those who found GDDP easy to use (OR: 6.6, 95% CI: 3.8-11.6), were
      more likely to utilize GDDP. Approximately 56% of the participants had utilized
      the GDDP at least once in the past 12 months. Approximately 85% of participants
      indicated that they would use GDDP if recommended by a physician. It is possible
      for FQHCs to be good venues for increasing awareness and utilization of GDDP.

PMID- 22643484
TI  - A methodological approach to improve the sexual health of vulnerable female
      populations: incentivized peer-recruitment and field-based STD testing.
AB  - INTRODUCTION: Transactional sex has been associated with increased risk of
      adverse health outcomes, including sexually transmitted infections (STIs).
      METHODS: Participants included female sex workers and men they recruited
      utilizing incentivized snowball sampling. Participants provided specimens for STI
      diagnostic testing and completed a semi-structured interview. RESULTS: Forty-four
      participants aged 19-65 were interviewed. Participants found self-sampling to be
      acceptable and overwhelmingly endorsed sampling outside of a clinic (90%) for
      reasons such as convenience, privacy, and lack of stigma. A substantial minority
      (38%) tested positive for at least one STI. CONCLUSION: Novel strategies may
      encourage sexual health care and prevent STIs among sex workers. High infection
      and screening acceptance rates across the sample suggests that individuals
      engaged in transactional sex would benefit from, and would be responsive to,
      community-based self-sampling for STI screening.

PMID- 22643485
TI  - The association of body mass index and perforation of the appendix in Puerto
      Rican children.
AB  - OBJECTIVE: Puerto Rico Department of Health lacks data on appendicitis since
      1996. We inquired about factors influencing perforation. METHODS: Retrospective
      study of risk factors among Puerto Rican children with appendicitis from 2002
      2008. RESULTS: One hundred and seventy records were reviewed. Appendiceal
      perforation = 38%. Median age was 10 years. Risk factors for perforation were age
      younger than five years, onset of symptoms more than 36 hours previously, public
      insurance, more than two examiners, and public hospital. Obese patients had a
      tendency to present with perforation (OR: 1.5 (0.6-3.5)). In the multivariate
      analysis, the only variables that remained significant were age younger than five
      years (OR: 10.2 (2.2-46.7)), and onset of symptoms more than 36 hours previously
      (OR: 5.9 (2.3-14.7)). CONCLUSION: Age younger than five years and onset of
      symptoms more than 36 hours previously were associated with perforation of the
      appendix. Body mass index for age percentile greater than the 95th had a tendency
      to present with perforation.

PMID- 22643486
TI  - Health reform and primary care capacity: evidence from Houston/Harris County,
      Texas.
AB  - This study estimated the possible surge in demand for primary care among the low
      income population in Houston/Harris County under the Patient Protection and
      Affordable Care Act, and related it to existing supply by safety-net providers. A
      model of the demand for primary care visits was developed based on California
      Health Interview Survey data and applied to the Houston/Harris County population.
      The current supply of primary care visits by safety-net providers was determined
      by a local survey. Comparisons indicate that safety-net providers in
      Houston/Harris County are currently meeting about 30% of the demand for primary
      care visits by the low-income population, and the rest are either met by private
      practice physicians or are unmet. Demand for primary care by this population is
      projected to increase by 30% under health reform leading to a drop in demand met
      by safety-net providers to less than 25%.

PMID- 22643487
TI  - What is the quality of preventive care provided in a student-run free clinic?
AB  - BACKGROUND: The quality of preventive care provided in student-run free clinics
      has not been well documented, although an increasing number of vulnerable
      populations seek care in these settings. OBJECTIVE: To examine the rate of
      preventive care services provided in one student-run free clinic compared with
      national data. Design. Cross-sectional chart review. PARTICIPANTS: Randomly
      selected patients seen between October 2008 and 2009. MAIN MEASURES: Preventive
      screening guidelines by the U.S. Preventive Services Task Force (USPSTF) and the
      American Diabetes Association (ADA). KEY RESULTS: Among 114 patient charts
      examined, 48 (42.1%) received an HIV test, which did not differ from national
      rates (40.8%, p=.78). Similarly, 63.3% of patients received a fasting blood
      glucose test (64.2%, p=.92). Among eligible patients, 59.6% received a fasting
      lipid panel and 54.6% a Pap smear; lower than national rates (86.6%, p<.001, and
      70.5%, p=.001 respectively), but not different compared with uninsured nationally
      (61.5%, p=.79, and 54.7%, p=.98). CONCLUSIONS: This student-run free clinic
      provided preventive services at comparable rates to national levels, but short of
      goals specified in Healthy People 2020.

PMID- 22643488
TI  - TennCare disenrollment and avoidable hospital visits in Davidson County,
      Tennessee.
AB  - The objective of this study was to determine if an association existed between
      the mid-2005 TennCare (Medicaid) disenrollment and increases in uninsured
      ambulatory care sensitive condition (ACSC) non-admitted ER visits and inpatient
      hospitalizations in Davidson County, Tennessee (= the city of Nashville).
      Logistic regression modeling, using an interactive term for insurance category x
      year, indicated that the effect of no insurance on ACSC ER visits increased by
      18% from 2003 to 2007 (p<.001), but no significant effect was found for uninsured
      ACSC inpatient hospitalizations. These greater odds of ACSC ER visits among
      uninsured patients were associated with a 60% increase in hospitals' bad debt
      write offs during this same time period. Therefore, the TennCare disenrollment
      was associated with increased likelihood of uninsured ACSC non-admitted ER visits
      and greater financial losses for Davidson County hospitals during this time
      period.

PMID- 22643489
TI  - Achieving excellence in community health centers: implications for health reform.
AB  - BACKGROUND: Existing studies tell us little about care quality variation within
      the community health center (CHC) delivery system. They also tell us little about
      the organizational conditions associated with CHCs that deliver especially high
      quality care. The purpose of this study was to examine the operational practices
      associated with a sample of high performing CHCs. METHODS: Qualitative case
      studies of eight CHCs identified as delivering high-quality care relative to
      other CHCs were used to examine operational practices, including systems to
      facilitate care access, manage patient care, and monitor performance. RESULTS:
      Four common themes emerged that may contribute to high performance. At the same
      time, important differences across health centers were observed, reflecting
      differences in local environments and CHC capacity. CONCLUSIONS: In the
      development of effective, community-based models of care, adapting care standards
      to meet the needs of local conditions may be important.

PMID- 22643490
TI  - Improving diabetes care in the uninsured: the success of the Access To Care
      program in Cook County, Illinois.
AB  - Previous studies have shown that the uninsured receive a lower level of care and
      that their uninsured status is a risk factor for poorly controlled diabetes
      mellitus (DM). The Access To Care (ATC) program in Cook County, Illinois provides
      care to uninsured individuals who do not qualify for other public aid. The aim of
      our study was to evaluate DM management at Loyola University Health System's ATC
      clinic. We compared ATC patients and insured patients at Loyola using processes
      of care and outcome measures outlined by the National Diabetes Quality
      Improvement Alliance. We found that the ATC group was equivalent in all processes
      of care. There were no differences in hemoglobin A1C or blood pressure while ATC
      patients had lower cholesterol. To our knowledge, this is the first study
      describing a clinic for the uninsured with a level of DM care and outcomes
      equivalent to those of insured individuals.

PMID- 22643493
TI  - A note from the editor.

PMID- 22643491
TI  - State policies and language access in California's HMOs: public reporting and
      regulation of HMOs' language services.
AB  - OBJECTIVE: Describe the status of language access services for California's
      limited English proficient (LEP) health maintenance organization (HMO) members
      within the context of voluntary public reporting and anticipated state
      regulation. STUDY DESIGN: Descriptive analysis of longitudinal data provided by
      health plans. METHODS: Retrospective, descriptive analysis of responses to
      voluntary annual/biennial surveys of commercial, Medicare, Medicaid, and Healthy
      Families HMOs, 2003-2008. RESULTS: From 2003 to 2008, during California's public
      reporting of HMO language services, the percentage of HMOs providing in-person
      interpretation free of charge to consumers increased to over 80% across all
      product lines. By 2008, the percentage of commercial HMO plans matching new LEP
      members to providers by language increased to 70%, while 79% provided telephone
      interpretation services in at least seven languages. CONCLUSIONS: Increasingly
      HMOs provide language access services for LEP Californians, perhaps resulting
      from public reporting and anticipated state regulation, although similar trends
      in other states cannot be ruled out.

PMID- 22643495
TI  - Laparoscopic management of bowel endometriosis: predictors of severe disease and
      recurrence.
AB  - BACKGROUND AND OBJECTIVES: The identification of highstage and recurrent cases of
      bowel endometriosis is critical, because these cases require careful surgical
      planning. We aim to describe the clinical characteristics of women with bowel
      endometriosis, our principles in laparoscopic  management of this pathology, and
      to identify predictors of severe disease and recurrence. METHODS: This was a
      retrospective study of 193 patients with pathologically confirmed bowel
      endometriosis. RESULTS: Predictors of higher-stage endometriosis include a
      history of  previous laparoscopic surgery (P=.04) and a presenting complaint of
      abnormal uterine bleeding (P=.01). The higher the stage of endometriosis, the
      more likely there would be coexistent urinary tract endometriosis (P=.02), a need
      for enterolysis (P=.002), ovarian cystectomy (P<.001), and bowel  resection
      (P=.01) performed during laparoscopy. Patients with higher body mass index (BMI)
      had significantly higher recurrence rates of endometriosis compared to those with
      lower BMI (P=.002). Within our cohort, 87% of our patients achieved amelioration
      of symptoms by the end of the first  postoperative month. CONCLUSIONS: Our study
      confirms that laparoscopic management of bowel endometriosis is safe and
      effective. We found 2 statistically significant predictors of higher-stage
      disease that should prompt careful surgical planning. Obesity is associated with
      a higher  rate of recurrence of endometriosis.

PMID- 22643496
TI  - Outcomes of surgical management of deep infiltrating endometriosis of the ureter
      and urinary bladder.
AB  - OBJECTIVES: To report the outcomes of surgical management of urinary tract
      endometriosis and discuss the choice between conservative and radical surgery.
      MATERIALS AND METHODS: We reviewed data concerning women managed for ureteral or
      bladder deep infiltrating endometriosis  in 5 surgical departments participating
      in the CIRENDO prospective database. Preoperative data, surgical procedure data,
      and postoperative outcomes were analyzed. RESULTS: Data from 30 women pooled in
      the database showed 15 women presenting with ureteral endometriosis, 14 women 
      with bladder nodules, and 1 with both types of lesions. Ureterolysis was
      performed in 14 cases; the ureter was satisfactorily freed in 10 of these. In 4
      women over 40 years old, who were undergoing definitive amenorrhea, moderate
      postoperative ureteral stenosis was tolerated and later improved  in 3 cases,
      while the fourth underwent secondary ureteral resection and ureterocystoneostomy.
      Primary ureterectomy was carried out in 4 women. Two cases of intrinsic ureteral
      endometriosis were found in 5 ureter specimens. Four complications were related
      to surgical procedures on ureteral  nodules, and 2 complications followed the
      removal of bladder endometriosis. Delayed postoperative outcomes were favorable
      with a significant improvement in painful symptoms and an absence of unpleasant
      urinary complaints, except for one patient with prolonged bladder denervation.
      CONCLUSION: Conservative surgery, in association with postoperative amenorrhea,
      can be proposed in a majority of cases of urinary tract endometriosis. Although
      the outcomes are generally favorable, the risk of postoperative complications
      should not be overlooked, as surgery tends to be performed in conjunction  with
      other complex procedures such as colorectal surgery.

PMID- 22643497
TI  - Laparoscopic major gynecologic surgery in patients with prior laparotomy bowel
      resection.
AB  - BACKGROUND AND OBJECTIVES: To review the success and morbidity of laparoscopic
      major gynecologic surgery in patients with prior laparotomy bowel resection.
      METHODS: Review of a prospective surgical database of all cases of laparoscopic
      major gynecologic surgery in  patients with prior laparotomy bowel resection. No
      cases were excluded. Bowel diagnoses and procedures were total colectomy for
      inflammatory bowel disease (4), partial colectomy for colon cancer (6), partial
      small bowel resection for obstruction (1), and Whipple for pancreatic cancer (2).
      Two patients had 3 prior laparotomies, 8 patients had 2 prior laparotomies, and
      3 patients had 1 prior laparotomy. All prior abdominal incisions were midline.
      Gynecologic diagnoses and procedures were laparoscopic cytoreduction for ovarian
      cancer (1), lsh/bso/staging for ovarian cancer (1),  lavh/bso/lymphadenectomy for
      endometrial cancer (4), and lavh/bso, lsh/bso, or bso for large ovarian mass (7).
      Median patient age was 57 years, median BMI was 31kg/m(2), and all patients had
      medical comorbidities. RESULTS: All 13 laparoscopic gynecologic surgeries were 
      successful without trocar insertion injury, conversion to laparotomy, and without
      enterotomy. Abdominal adhesions were present in all cases. Median operative time
      was 2 hours, median blood loss was 100cc, and median hospital stay was 1 day.
      There were no postoperative complications. CONCLUSION: Laparoscopic major
      gynecologic surgery in patients with prior laparotomy bowel resection is feasible
      for experienced laparoscopic surgeons.

PMID- 22643499
TI  - Laparoscopic supracervical hysterectomy versus laparoscopic-assisted vaginal
      hysterectomy.
AB  - OBJECTIVES: To compare the incidence of perioperative complications and
      postoperative healthcare utilization and costs in laparoscopic supracervical
      hysterectomy (LSH) versus laparoscopic-assisted vaginal hysterectomy (LAVH)
      patients. METHODS: Women 18 years with LSH or LAVH were extracted using a large
      national commercial claims database from 1/1/2007 through 9/30/2008. Outcome was
      perioperative complications and gynecologic-related postoperative resource use
      and costs. Multivariate analysis was performed to compare postsurgical outcomes
      between the cohorts. RESULTS: The final sample consisted of 6,198 LSH patients
      and 14,181 LAVH patients. LSH patients were significantly more likely to have
      dysfunctional uterine bleeding and leiomyomas and less likely to have
      endometriosis and prolapse as the primary diagnosis, and also significantly more
      likely to have a uterus that weighed 250 grams than LAVH patients. Compared with
      LAVH patients, LSH patients had significantly lower overall infection rates (7.4%
      versus 6.2%, P .002) and lower total gynecologic related postoperative costs
      ($252 versus $385, P .001, within 30 days of follow-up and $350 versus $569, P
      .001, within 180 days of follow-up). Significant cost differences remained
      following multivariate adjustment for patient characteristics. CONCLUSIONS: LSH
      patients demonstrated fewer perioperative complications and lower GYN-related
      postoperative costs compared to LAVH patients.

PMID- 22643498
TI  - Vaginal-assisted laparoscopic radical hysterectomy: rationale, technique,
      results.
AB  - OBJECTIVE: Total laparoscopic radical hysterectomy (TLRH) makes it difficult to
      resect adequate vaginal cuff according to tumor size and to avoid tumor spread
      after opening the vagina. Laparoscopic-assisted radical vaginal hysterectomy
      (LARVH) is associated with higher risk for urologic complications. METHODS: The
      vaginal-assisted laparoscopic radical hysterectomy (VALRH) technique comprises 3
      steps: (1) comprehensive laparoscopic staging, (2) creation of a tumoradapted
      vaginal cuff, and (3) laparoscopic transsection of parametria. We retrospectively
      analyzed data of 122 patients who underwent VALRH for early stage cervical cancer
      (n=110) or stage II endometrial cancer (n=12) between January 2007 and December
      2009 at Charite University Berlin. RESULTS: All patients underwent VALRH without
      conversion. Mean operating time was 300 minutes, and mean blood loss was 123cc.
      On average, 36 lymph nodes were harvested. Intra- and postoperative complication
      rates were 0% and 13.1%, respectively. Resection was in sound margins in all
      patients. After median follow-up of 19 months, disease-free survival and overall
      survival for all 110 cervical cancer patients was 94% and 98%, and for the
      subgroup of patients (n=90) with tumors <=pT1b1 N0 V0 L0/1 R0, 97% and 98%,
      respectively. CONCLUSION: VALRH is a valid alternative to abdominal radical
      hysterectomy and LARVH in patients with earlystage cervical cancer and
      endometrial cancer stage II with minimal intraoperative complications and
      identical oncologic outcomes.

PMID- 22643500
TI  - Hysterosalpingography versus sonohysterography for intrauterine abnormalities.
AB  - OBJECTIVE: The hysterosalpingogram is commonly used to evaluate the uterine
      cavity and the fallopian tubes in the workup of infertile couples. The
      sonohysterogram is gaining popularity as part of this evaluation. This study
      compares hysterosalpingography to sonohysterography  for the detection of polyps,
      cavitary fibroids, adhesions, and septae in infertile patients. METHODS: We
      conducted a retrospective chart review of 149 infertility patients seen at a
      University Hospital Center, divisions of Reproductive Endocrinology and
      Interventional Radiology.  Patients underwent hysterosalpingography and
      sonohysterography as part of their infertility evaluation. The reports were
      reviewed and findings like polyps, fibroids, adhesions, and septae were compared
      to the findings obtained at the time of hysteroscopy. Sensitivity, specificity,
      and accuracy  of radiologic tests were the main outcome measures. RESULTS: The
      sensitivity of hysterosalpingography and sonohysterography was 58.2% and 81.8%,
      respectively. The specificity for hysterosalpingography and sonohysterography was
      25.6% and 93.8%. The differences in sensitivity and  specificity were both
      statistically significant. Hysterosalpingography had a general accuracy of 50.3%,
      while sonohysterography had a significantly higher accuracy of 75.5%. CONCLUSION:
      Although hysterosalpingography is the standard screening test for the diagnosis
      of tubal infertility  and can provide useful information about the uterine
      cavity, sonohysterography is more sensitive, specific, and accurate in the
      evaluation of the uterine cavity.

PMID- 22643501
TI  - Laparoscopic loop ileostomy reversal: reducing morbidity while improving
      functional outcomes.
AB  - INTRODUCTION: Loop ileostomy reduces the morbidity associated with pelvic sepsis.
      However, its reversal carries a 10% to 30% complication rate. We present our
      technique for laparoscopic ileostomy closure. METHODS: We conducted a
      retrospective chart review of subjects  undergoing laparoscopic-assisted loop
      ileostomy closure between 2006 and 2009. Operating time, length of hospital stay,
      return of bowel function, and complication rates were assessed. RESULTS: There
      were 24 (13 males) patients. Average age was 63 with a BMI of 25.9. Eighteen
      (75%)  had a planned loop ileostomy, and 6 (25%) were emergent. Average time to
      reversal was 135 days. Average length of surgery was 79 minutes (range, 48 to
      186), average stay was 4 days and return to bowel function was 3.6 days. We had
      no wound infections. Our complication rate was 29% (n=7), and  reoperation rate
      was 12.5% (n=3). Only 1 major complication occurred, an anastomotic dehiscence.
      CONCLUSION: A thorough, well-visualized lysis of adhesions and mobilization of
      the stoma and surrounding small bowel is the main advantage of our approach. We
      had no wound infections  and no reoperation for bowel obstruction, which we feel
      is a direct advantage of our technique. Our complication rate and surgical time
      are comparable to those of the open technique.

PMID- 22643502
TI  - Blood transfusion in patients with sickle cell disease requiring laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Surgery in patients with sickle cell disease is associated with high
      morbidity. To reduce this high morbidity, different preoperative transfusion
      regimens were introduced. However, blood transfusion is associated with problems.
      This prospective study aims to establish  the safety of conducting laparoscopic
      cholecystectomy without transfusion in sickle cell disease patients. METHODS:
      Forty patients (16 males and 24 females; mean age 26.6 years) undergoing
      laparoscopic cholecystectomy for cholelithiasis were divided into 2 matched
      groups:  Group I "no transfusion" (n=24 patients; 60%) and Group II "transfusion"
      (n=16; 40%). In Group II, 9 patients (22.5%) received a simple transfusion and 7
      (17.5%) a partial exchange transfusion. RESULTS: Group II patients had
      significantly higher levels of  Hb-S prior to transfusion. They developed a
      significantly higher complication rate (25% vs. 0%) and subsequently longer
      hospital stay (3.9+/-2 vs. 2.1+/-1.4). Moreover, there was no significant
      difference in the complications between the simple transfusion and partial 
      exchange transfusion subgroups. CONCLUSION: Surgery in SCD patients is safe
      without a preoperative blood transfusion. Moreover, preoperative blood
      transfusion is associated with significantly higher postoperative complications
      and longer hospital stay. Hence, a "no transfusion"  policy is recommended.

PMID- 22643503
TI  - Laparoscopic sleeve gastrectomy versus laparoscopic adjustable gastric banding
      for the treatment severe obesity in high risk patients.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has emerged as an alternative
      restrictive bariatric procedure to the most popular laparoscopic adjustable
      gastric banding (LAGB). We analyze and compare the clinical and weight loss
      outcomes of LSG versus LAGB for the treatment of severe obesity in high-risk
      patients. METHODS: Forty severely obese veterans (20/group) received either LSG
      or LAGB and were followed prospectively for 2 years. Outcome measures included
      operating room (OR) time, estimated blood loss (EBL), length of hospital stay
      (LOS), morbidity, mortality, reoperations, readmission rates, and weight loss
      over time. RESULTS: The cohort primarily comprised high-risk and older male
      veterans. Patient's baseline demographics were similar between groups. LSG was
      associated with prolonged OR time (116+/-31 vs. 94+/-28min), higher EBL (34+/-28
      vs. 17+/-19mL), and LOS (2+/-.9 vs. 1+/-.4days) when compared with LAGB. Minor
      morbidity and readmissions were similar between groups, while no major morbidity,
      reoperations, or mortality occurred. Total weight and BMI decreased significantly
      after surgery in both groups (LSG: 302+/-52 to 237lbs and 45+/-5 to 36+/-5kg/m(2)
      vs. LAGB: 280+/-36 to 231+/-29lbs and 43+/-5 to 36+/-5kg/m(2), respectively).
      Total weight loss was superior in the LSG vs. LAGB group at 2 years (TWL=65+/-24
      vs. 49+/-28 lbs (P=.03); %EWL=51+/-20 vs. 46+/-23%; %EBMI loss=48+/-22 vs. 45+/
      23%, and %BWL=21+/-8 vs. 17+/-9%, respectively). CONCLUSION: In severely obese
      and high-risk patients, laparoscopic sleeve gastrectomy provides superior total
      weight loss at 2 years.

PMID- 22643504
TI  - Alvimopan addition to a standard perioperative recovery pathway.
AB  - BACKGROUND AND OBJECTIVES: Alvimopan, a peripherally acting mu-opioid receptor
      antagonist, decreased time to gastrointestinal recovery and hospital length of
      stay in open bowel resection patients in Phase 3 trials. However, the benefit in
      laparoscopic colectomy patients remains  unclear. METHODS: A retrospective case
      series review was performed to study addition of alvimopan to a well-established
      standard perioperative recovery pathway for elective laparoscopic colectomy. The
      main outcome measures were length of stay and incidence of charted postoperative 
      ileus. Wilcoxon and chi-square tests were used to calculate P values for length
      of stay and postoperative ileus endpoints, respectively. RESULTS:
      Demographic/baseline characteristics from the 101 alvimopan and 64 pre-alvimopan
      control patients were generally comparable. Mean length  of stay in the alvimopan
      group was 1.55 days shorter (alvimopan, 2.81+/-0.95 days; control, 4.36+/-2.4
      days; P<.0001). The proportion of patients with postoperative ileus was lower in
      the alvimopan group (alvimopan, 2%; control, 20%; P<.0001). CONCLUSION: In this 
      case series, addition of alvimopan to a standard perioperative recovery pathway
      decreased length of stay and incidence of postoperative ileus for elective
      uncomplicated laparoscopic colectomy. The improvement in the mean length of stay
      for patients who receive alvimopan is a step forward in  achieving a fasttrack
      surgery model for elective laparoscopic colectomies.

PMID- 22643505
TI  - Minimally invasive parathyroidectomy in patients with previous endocrine surgery.
AB  - OBJECTIVE: Previous endocrine neck surgery (PENS) in patients with sporadic
      primary hyperparathyroidism (PHP) is considered a contraindication for minimally
      invasive parathyroidectomy (MIP). The purpose of our study was to determine the
      effectiveness of MIP in such patients. METHODS: From January 2004 to December
      2009, 270 patients with PHP were treated in our department; 30 had had PENS in
      the past. Eighteen were selected to have MIP, while the other 12 had traditional
      neck explorations. Selection criteria for MIP were unilateral single- or double
      gland  disease localized preoperatively with at least 2 concordant imaging
      techniques and patient informed consent. Imaging studies included high-resolution
      neck ultrasound and sestamibi scan in most patients, and CT scan, selective
      venous sampling, and MRI in 7 patients. Unilateral explorations  via a lateral
      approach with the patients under local (UALA in 13 patients), general (MIP in 4
      patients), or local followed by general anesthesia (1 patient) were performed.
      RESULTS: Sixteen of the 17 patients became normocalcemic after the operation.
      There was no conversion to traditional  exploration. A single adenoma was found
      in 16 patients and hyperplasia in one. One patient underwent a successful
      parathyroidectomy 8 months later via mesothoracoscopy, because the parathyroid
      gland was localized correctly but was beyond access via neck. There were no
      postoperative complications.  Mean duration of the procedure and length of stay
      were similar to MIP in patients without PENS. Mean follow-up of 33 months (range,
      4 to 70) did not reveal any recurrence. CONCLUSION: These results illustrate that
      MIP is a valuable option in select patients with sporadic PHP and  PENS.
      Localization with 2 or more concordant imaging techniques could avoid
      intraoperative sestamibi or qPTH testing with low morbidity (0%), high
      biochemical cure rate (100% in this series), rapid recovery, and finally
      substantially lower the cost of the procedure.

PMID- 22643506
TI  - A safe quick technique for placement of the first access port for creation of
      pneumoperitoneum.
AB  - INTRODUCTION: Closed and open techniques for creation of pneumoperitoneum are
      being used simultaneously with varying frequencies. Some studies analyzing slight
      modifications to both approaches have been published and others are under way. We
      conducted this study to eliminate  some of the disadvantages of the open
      technique, an already proven safer technique. PATIENTS & METHODS: In a total of
      1250 consecutive patients, who underwent various laparoscopic procedures, a
      modified open technique was used. This technique involves identification and
      incision  of a point at a junction of the umbilical stalk and linea alba
      infraumbilically. With this technique, penetration of a blunt trocar was possible
      under direct vision with minimal and controlled axial force. Time needed to
      induce pneumoperitoneum, intraoperative (vascular and other organ injury)  and
      postoperative complications were recorded, and data were analyzed. RESULTS:
      Intraabdominal access was successfully achieved in all cases without any vascular
      or solid organ injury except in 3 (0.24%) cases. In these 3 cases, the procedure
      failed due to severe adhesions, because  of previous abdominal surgeries. Mean
      time taken to induce pneumoperitoneum was 4.0 minutes (range, 2 to 9.5), while
      time required to close the first access port was 4.5 minutes (range, 3 to 8).
      Enterotomy occurred in 2 (0.16%) cases, while a postoperative port-site hernia
      occurred in 2 (0.16%)  cases. Port-site infection occurred in 6 (0.48%) cases,
      and port-site hematoma in 4 (0.32%) cases. Gas spillage was recorded in only 6
      (0.48%) cases. CONCLUSION: We recommend a modified open technique as the
      technique of choice in all cases requiring laparoscopic surgery in general  and
      developing countries in particular where intraabdominal adhesions are not
      uncommon.

PMID- 22643507
TI  - Comparison of two core biopsy techniques before and after laparoscopic
      cryoablation of small renal cortical neoplasms.
AB  - INTRODUCTION: Cryoablation is an acceptable treatment option for small renal
      cortical neoplasms (RCN). Unlike extirpative interventions, intraoperative needle
      biopsy is the only pathologic data for ablated tumors. It is imperative that
      sampled tissue accurately captures pathology.  We studied the optimal
      intraoperative needle core biopsy protocol for small RCN during laparoscopic
      renal cryoablation (LCA). METHODS: Patients with RCN<4cm underwent intraoperative
      biopsy during LCA. Four biopsy cores were taken per tumor, 2 before and 2 after
      LCA by using both  a standard and modified technique. Standard technique: needle
      biopsy device was deployed after insertion into the renal tissue at a depth of
      5mm. Modified technique: needle biopsy device was deployed 1mm outside of the
      renal tissue. Biopsies were examined and compared with reference standard 
      pathology. Percentage agreement was calculated across biopsy types (standard vs.
      modified) and time points (pre- vs. postcryoablation). Logistic regression was
      used to identify factors impacting biopsy accuracy. RESULTS: Thirty patients with
      33 RCNs underwent LCA. The mean patient  age was 69.1+/-8.0yrs, and mean tumor
      size was 2.3+/-0.7cm. No significant bleeding resulted from biopsies. A
      definitive diagnosis was made in 31/33 RCNs (94.0%). Ten tumors (30.3%) were
      benign, 21 (63.7%) were malignant, and 2 (6.0%) were nondiagnostic. Biopsy length
      was significantly  longer using the standard vs. modified technique with mean
      lengths of 9.3mm vs. 7.0mm, respectively (P=.02). Highest agreement was seen in
      preablation biopsies (90.3%). A significant association with agreement was seen
      for younger age (P=.05) and larger tumor size (P=.02). CONCLUSIONS: Younger age
      and larger tumor size were associated with improved accuracy. Preoperative
      sampling resulted in superior accuracy and the standard technique resulted in
      significantly longer cores. Use of preablation standard biopsy technique may
      result in the most accurate pathologic diagnosis  for patients undergoing
      cryoablation for small RCNs.

PMID- 22643508
TI  - Computed tomography appearance of Hem-o-lok clips in patients who have undergone
      laparoscopic nephrectomy or nephroureterectomy.
AB  - BACKGROUND AND OBJECTIVES: Hem-o-lok clips are safe and reliable for controlling
      the renal vasculature. We retrospectively evaluated the CT appearance of Hem-o
      lok clips in patients who had undergone laparoscopic radical nephrectomy (LRN) or
      nephroureterectomy (LRU) as well as  their appearance on ex vivo CT scans.
      METHODS: Between January 2006 and December 2006, 19 patients underwent LRN or
      LRU, and their CT images were reviewed within 5 postoperative months. The Hem-o
      lok clips were radiopaque in all of the patients' CT images, and their
      radiodensity  value was 222 Hounsfield Units (HU). To confirm that Hem-o-lok
      clips are radiopaque on CT images, an ex vivo CT scan was performed. RESULTS: We
      confirmed that these clips are radiopaque on CT images and that they have a
      radiodensity of 223 HU. CONCLUSION: We conclude  that the Hem-o-lok clips are
      radiopaque on CT images. It is important for urologists and radiologists to be
      aware of the CT appearance of Hem-o-lok clips when following up patients who have
      undergone LRN or LRU.

PMID- 22643509
TI  - Robotic partial nephrectomy using robotic bulldog clamps.
AB  - BACKGROUND AND OBJECTIVES: The need for a skilled assistant to perform hilar
      clamping during robotic partial nephrectomy is a potential limitation of the
      technique. We describe our experience using robotic bulldog clamps applied by the
      console surgeon for hilar clamping. METHODS: A total of 60 consecutive patients
      underwent robotic partial nephrectomy, 30 using laparoscopic bulldog clamps
      applied by the assistant and 30 using robotic bulldog clamps applied with the
      robotic Prograsp instrument. Perioperative outcomes were compared between groups.
      RESULTS: All 30 patients underwent successful hilar clamping during robotic
      partial nephrectomy using robotic bulldog clamps with no intraoperative
      complications and without the need for readjustment/reclamping. Robotic bulldog
      clamps provided adequate ischemia even for tumors >4  cm, hilar, endophytic,
      multiple tumors, and multiple renal arteries. Both groups had similar baseline
      characteristics. Perioperative outcomes with robotic bulldog clamps were at least
      comparable to the laparoscopic bulldog group, with a trend to lower console time,
      warm ischemia time, and  estimated blood loss. CONCLUSIONS: Use of robotically
      applied bulldog clamps is a safe and feasible method of hilar occlusion during
      robotic partial nephrectomy; they perform at least as well as laparoscopic
      bulldog clamps while allowing the console surgeon greater autonomy and  precision
      for hilar clamping.

PMID- 22643510
TI  - A novel laparoscopic tissue retrieval device.
AB  - BACKGROUND AND OBJECTIVES: A persistent problem in operative laparoscopy is the
      removal of laparoscopically resected tissue specimens. This study is a
      consecutive series demonstrating a device designed to facilitate the removal of
      laparoscopically resected tissue specimens. METHODS: Forty-two patients met the
      criteria for inclusion in this study. These patients included gynecologic
      operative laparoscopy patients with a laparoscopically resected tissue specimen
      placed in a tissue retrieval sac. The sac could not to be removed from a
      subumbilical trocar  incision with axial traction. The device was placed and an
      attempt was made to remove the sac/specimen. When successful, the wound was
      inspected for a fascial defect and closed, and if unsuccessful the wound was
      enlarged to remove the tissue specimen. RESULTS: Thirty-four patients  had
      successful removal of the laparoscopic tissue specimen. In 8 patients, the device
      was not successful. No adverse intraoperative outcomes occurred. Three patients
      had superficial postoperative wound infection treated successfully with
      outpatient oral antibiotic therapy. There were no other  postoperative
      complications. CONCLUSION: This novel medical device allows an easy and effective
      means to remove trapped laparoscopic tissue retrieval sacs. Prudent use of this
      device appears to convey no increased risk of adverse surgical outcomes.

PMID- 22643511
TI  - Preoperative warm-up using a virtual reality simulator.
AB  - BACKGROUND AND OBJECTIVES: All modern surgical procedures require a high level of
      cognitive and psychomotor skills achieved using different training methods, but
      could be influenced by fatigue and other psychological factors. We evaluated the
      effect of warm-up exercises on operative  laparoscopic performances. METHODS: The
      surgical team operated on a consecutive series of 20 patients with gallstones.
      Patients were randomly allocated in 2 groups: group A to be operated on without
      warm-up exercises and group B to be operated on after a short-term warm-up. All 
      the patients were operated on by the same surgical team. The full-time records of
      the operation were analyzed by 2 independent reviewers. A modified simplified
      Global Rating Score (GRS) was used to assess the surgical procedures. A training
      module using the Lap Mentor simulator was designed  for the warm-up. RESULTS:
      Better performances were noted by both observers in group B only regarding
      "Respect for tissue" scores (3.75 0.16 vs 4.43 0.20, P=.021 and 3.87 0.22 vs 4.57
      0.20, P=.041) achieving significant or marginally significant differences for all
      categories;  GRS scores for "time and motion" and "overall impression" tend to be
      better after warm-up, but differences failed to reach statistical significance in
      our series. CONCLUSION: Surgeons, even the most experienced in laparoscopic
      surgery, can increase specific  psychomotor skills associated with a laparoscopic
      environment by doing simple exercises on a virtual reality simulator, just before
      an operation. These improvements are reflected in more accurate handling of
      tissue during laparoscopic cholecystectomy.

PMID- 22643512
TI  - Fimbrial ectopic pregnancy following tubal anastomosis.
AB  - The incidence of ectopic pregnancy in the general population is approximately 1%.
      This risk increases to 5% following tubal anastomosis. Ectopic pregnancy may
      cause life-threatening hemorrhage. Morbidity and mortality associated with an
      extrauterine pregnancy are directly related to  the length of time required for
      diagnosis and treatment. Laparoscopy is the gold standard for surgical management
      in these cases. This report deals with the case of a rare form of ectopic
      pregnancy following tubal anastomosis.

PMID- 22643513
TI  - Gastric prolapse with pseudocysts following laparoscopic adjustable gastric
      banding.
AB  - INTRODUCTION: Laparoscopic adjustable gastric banding (LAGB) is a reversible
      method of surgical gastric restriction. Following LAGB, the adverse event most
      commonly necessitating subsequent reoperation is prolapse of the gastric corpus
      or fundus above the band. A review of the  medical literature reveals no reports
      of nonpancreatic pseudocysts being associated with this adverse event.
      Nonpancreatic pseudocysts, encountered during revisional bariatric surgery should
      be considered a cause of irreducible gastric prolapse. CASE REPORT: We report the
      case of  a 41-year-old Caucasian female who underwent laparoscopic surgery to
      revise an adjustable gastric band and to repair an anterior gastric prolapse.
      Intraoperatively, 2 pseudocysts were found on the gastric fundus above the band
      in association with the gastric prolapse. The pseudocysts were  resected, the
      gastric prolapse was reduced, and the band was left in place. The patient
      recovered uneventfully. CONCLUSION: Nonpancreatic pseudocysts may be associated
      with gastric prolapse in patients who have undergone LAGB. These pseudocysts can
      often be excised laparoscopically  without violating the gastric lumen. This
      atypical presentation of gastric prolapse may pose a diagnostic and therapeutic
      challenge as these patients may.

PMID- 22643514
TI  - Laparoscopic repair of chronic traumatic diaphragmatic hernia using biologic mesh
      with cholecystectomy for intrathoracic gallbladder.
AB  - BACKGROUND AND OBJECTIVES: Diaphragmatic rupture is a serious complication of
      both blunt and penetrating abdominal trauma. In the acute setting, delay in
      diagnosis can lead to severe cardiovascular and respiratory compromise. Chronic
      cases can present years later with a plethora  of clinical symptoms. Laparoscopic
      techniques are being increasingly utilized in the diagnosis and treatment of
      traumatic diaphragmatic hernias. METHOD: We describe a case of a 70-year-old
      female who presented with signs and symptoms of a small bowel obstruction. She
      was ultimately  found to have an obstruction secondary to a chronic traumatic
      diaphragmatic hernia with an intrathoracic gallbladder and incarcerated small
      intestine. A cholecystectomy and diaphragmatic hernia repair were both performed
      laparoscopically. This case report presents an atypical cause of bowel 
      obstruction and reviews the current literature on laparoscopic management of
      traumatic diaphragmatic hernias. RESULTS AND CONCLUSION: Laparoscopy is
      increasingly used in the diagnosis and treatment of traumatic diaphragmatic
      hernias with good results.

PMID- 22643515
TI  - Combined robotic-assisted laparoscopic prostatectomy and laparoscopic
      hemicolectomy.
AB  - A 60-year-old man with prostatic adenocarcinoma and a synchronous tubulovillous
      adenomatous polyp of the colon underwent a successful robotic radical
      prostatectomy combined with a laparoscopic right hemicolectomy. We describe the
      initial report of this combined, minimally invasive procedure  involving separate
      organ systems and surgical disciplines, and describe our technique.

PMID- 22643516
TI  - Laparoscopic repair of colonic anastomotic leak in an elderly patient.
AB  - BACKGROUND: Laparoscopy to repair iatrogenic colonoscopic perforation of the
      colon has proven to be a safe, effective, and reproducible means to treat these
      potentially devastating emergencies. The use of the laparoscope provides
      exceptional diagnostic yield, and under the hand  of a trained surgeon, produces
      excellent therapeutic results while minimizing recovery time for the patient.
      METHODS: We report the case of an 86-year-old man who underwent emergent
      laparoscopic repair of a postoperative anastomotic leak following sigmoid
      colectomy. RESULTS: The patient underwent laparoscopic oversewing of a colonic
      anastomotic leak, omental patch, and diverting loop ileostomy. The patient
      recovered fully from his emergency procedure without any further complications.
      CONCLUSION: Laparoscopic surgery can be extended to a wider variety  of
      colorectal emergencies in a carefully selected group of patients, including the
      elderly.

PMID- 22643517
TI  - Meckel's diverticulum with small bowel obstruction presenting as appendicitis in
      a pediatric patient.
AB  - BACKGROUND: Meckel's diverticulum is a congenital anomaly resulting from
      incomplete obliteration of the omphalomesenteric duct. The incidence ranges from
      0.3% to 2.5% with most patients being asymptomatic. In some cases, complications
      involving a Meckel's diverticulum may mimic  other disease processes and obscure
      the clinical picture. METHODS: This case presents an 8-year-old male with
      abdominal pain, nausea, and vomiting and an examination resembling appendicitis.
      RESULTS: A CT scan revealed findings consistent with appendicitis with dilated 
      loops of small bowel. During laparoscopic appendectomy, the appendix appeared
      unimpressive, and an inflamed Meckel's diverticulum was found with an adhesive
      band creating an internal hernia with small bowel obstruction. The diverticulum
      was resected after the appendix was removed. CONCLUSION: The incidence of an
      internal hernia with a Meckel's diverticulum is rare. A diseased Meckel's
      diverticulum can be overlooked in many cases, especially in those resembling
      appendicitis. It is recommended that the small bowel be assessed in all
      appendectomy cases for a pathological Meckel's  diverticulum.

PMID- 22643518
TI  - Laparoscopic treatment of bowel obstruction due to a bezoar in a Meckel's
      diverticulum.
AB  - BACKGROUND AND OBJECTIVES: Meckel's diverticulum is a common anomaly of the
      gastrointestinal tract that may result in gastrointestinal bleeding,
      diverticulitis, and small bowel obstruction. This report describes the use of
      laparoscopy to treat a rare complication of Meckel's  diverticulum-small bowel
      obstruction due to phytobezoar impaction. More generally, it provides an example
      of the feasibility and utility of a laparoscopic approach to small bowel
      obstructions of unknown causes. METHODS: A 34-year-old male presented to the
      emergency department  complaining of episodic abdominal pain and vomiting. He had
      no history of abdominal surgery. His vital signs were stable, and his abdomen was
      distended, but only mildly tender. He had no abdominal wall hernias on
      examination. Imaging was consistent with small bowel obstruction. He was brought 
      to the operating room where laparoscopy revealed a Meckel's diverticulum with an
      impacted phytobezoar as the source of obstruction. The diverticulum was resected
      and the phytobezoar removed laparoscopically. RESULTS: The patient recovered well
      and was discharged home on the third  postoperative day, tolerating a regular
      diet. CONCLUSIONS: Phytobezoar impaction in a Meckel's diverticulum causing small
      bowel obstruction is a rare event. It can be effectively treated
      laparoscopically. This case provides an example of the potential utility of
      laparoscopy in treating  small bowel obstructions of unclear etiology.

PMID- 22643519
TI  - Laparoscopic appendectomy for torsed appendix presenting as an acute abdomen in
      an infant female.
AB  - BACKGROUND: Torsion of an otherwise normal appendix vermiformis is exceedingly
      rare and usually presents with symptoms consistent with acute appendicitis. We
      present the unusual case of an infant girl who was admitted with right lower
      quadrant pain and focal peritonitis who was  found to have appendiceal torsion on
      laparoscopy. CASE REPORT: An 11-week-old girl was brought to the emergency
      department with a 48-hour history of abdominal pain, emesis, low-grade fever, and
      focal right lower quadrant tenderness. Sonography found a noncompressible
      distended appendix  in the right lower quadrant. Upon laparoscopy, a torsed,
      necrotic appendix vermiformis was found. Appendectomy was performed, and the
      patient recovered uneventfully. CONCLUSION: In an infant girl with lower
      abdominal pain, the differential diagnosis should include torsed appendix 
      besides more common causes, such as torsed ovary, intussusception, or small bowel
      volvulus. Ultrasound is useful for planning the operative approach.

PMID- 22643520
TI  - Laparoscopic removal of a copper intrauterine device from the sigmoid colon.
AB  - IUD translocation to the sigmoid colon after uterine perforation is a rare but
      serious event. Removal of the IUD in such a situation has been recommended
      because of the risk of complication, such as fistula formation and colonic
      perforation. We present the case of a 43-year-old female  with a copper T380A IUD
      embedded in the sigmoid colon, which was removed with minimally invasive
      techniques.

PMID- 22643521
TI  - Minimally invasive management of lesser sac bronchogenic cyst.
AB  - Bronchogenic cysts rarely develop in the abdomen they typically reside in the
      mediastinum. We present a unique case of a bronchogenic cyst within the lesser
      sac. Endoscopic ultrasound proved to be a critical diagnostic tool, and the
      patient underwent a laparoscopic resection of the  lesion.

PMID- 22643522
TI  - Ureteric duplication is not a contraindication for robot-assisted laparoscopic
      radical cystoprostatectomy and intracorporeal Studer pouch formation.
AB  - OBJECTIVES: Ureteric duplication is a rarely seen malformation of the urinary
      tract more commonly seen in females. MATERIALS AND METHODS: We report 2 cases of
      robot-assisted laparoscopic radical cystoprostatectomy (RALRCP) with bilateral
      extended pelvic lymph node dissection and intracorporeal Studer pouch formation
      in patients with duplicated right ureters. RESULTS: Two male patients (53 and 68
      years old) underwent transurethral resection of a bladder tumor that revealed
      high-grade muscle invasive transitional cell carcinoma, with no metastases. We
      performed RALRCP and intracorporeal Studer pouch formation. A duplicated right
      ureter was observed during the procedures in both patients. Left ureter distal
      segment was spatulated 2cm long and anastomosed using running 4/0 Vicryl to the
      right ureter at its bifurcation where it forms a single lumen without
      spatulation. All 3 ureters were catheterized individually. A Wallace type uretero
      ileal anastomosis was performed between the ureters and the proximal part of the
      Studer pouch chimney. Although ureteric frozen section analysis suggested
      ureteric carcinoma in situ in patient 1, postoperative pathologic evaluation was
      normal. Frozen section and final postoperative pathologic evaluations were normal
      in patient 2. CONCLUSIONS: Duplicated ureters might be underdiagnosed on CT. The
      presence of a duplicated ureter is not a contraindication to RALRCP and
      intracorporeal Studer pouch formation. The da Vinci-S surgical robot is very safe
      for performing this complicated procedure. Frozen section analysis of ureters
      during radical cystectomy for bladder cancer might not reliably diagnose the
      pathologic condition and might overestimate the disease in the ureters.

PMID- 22643523
TI  - Testicular vein syndrome and its treatment with a laparoscopic approach.
AB  - BACKGROUND AND OBJECTIVES: Testicular vein syndrome (TVS) is a rare cause of
      ureteral obstruction. Only 5 previous cases are on record in the literature, and
      no review exists on this topic to date. Laparoscopic treatment has never been
      mentioned in the management of TVS. MATERIALS AND METHODS: We reviewed the
      literature related to this unusual entity to clarify the preoperative evaluation
      and the management of TVS. For this purpose, the data related to all the 5 cases
      previously reported so far in the English literature have been reviewed. Also, we
      report the sixth case of TVS, and the first patient to be successfully treated
      with the laparoscopic approach. This was a 37-year-old male with a 6-month
      history of left loin pain. Preoperative diagnosis was confirmed by CT-Urography.
      RESULTS: Our patient underwent laparoscopic  excision of the left testicular vein
      followed by ureteroureterostomy in a single sitting. The laparoscopic
      transperitoneal approach was used. Histopathological examination of the vein
      showed normal venous tissue. This is the sixth reported case of TVS and the first
      to be successfully treated  with a laparoscopic technique. CONCLUSIONS: A
      laparoscopic approach is safe and effective for treating patients with TVS with
      the common advantages of minimal invasiveness and better visualization of the
      complex anatomy of the retroperitoneum. Thus, it should be the treatment of 
      choice for TVS.

PMID- 22643524
TI  - Renaissance of Minilaparoscopy in the NOTES and single port era.

PMID- 22643536
TI  - Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes:
      a meta-analysis.
AB  - OBJECTIVE: Oral antidiabetic drugs (including metformin and sulfonylurea) may
      play a role in the relationship between type 2 diabetes and cancer. To quantify
      the association between metformin and sulfonylurea and the risk of cancer, we
      performed a meta-analysis of available studies on the issue. MATERIALS AND
      METHODS: We performed a MEDLINE search for observational studies that
      investigated the risk of all cancers and specific cancer sites in relation to use
      of metformin and/or sulfonylurea among patients with type 2 diabetes mellitus.
      Fixed- and random-effect models were fitted to estimate the summary relative risk
      (RR). Between-study heterogeneity was tested using chi(2) statistics and measured
      with the I(2) statistic. Publication bias was evaluated using funnel plot and
      Egger's regression asymmetry test. RESULTS: Seventeen studies satisfying
      inclusion criteria and including 37,632 cancers were evaluated after reviewing
      401 citations. Use of metformin was associated with significantly decreased RR of
      all cancers (summary RR 0.61, 95% confidence interval [CI] 0.54-0.70), colorectal
      cancer (0.64, 95% CI 0.54-0.76), and pancreatic cancer (0.38, 95% CI 0.14-0.91).
      With the exception of colorectal cancer, significant between-study heterogeneity
      was observed. Evidence of publication bias for metformin-cancer association was
      also observed. There was no evidence that metformin affects the risk of breast
      and prostate cancers, nor that sulfonylurea affects the risk of cancer at any
      site. CONCLUSIONS: Metformin, but not sulfonylurea, appears to reduce subsequent
      cancer risk. This has relevant implications in light of the exploding global
      epidemic of diabetes.

PMID- 22643537
TI  - Approval summary: imatinib mesylate for one or three years in the adjuvant
      treatment of gastrointestinal stromal tumors.
AB  - On January 31, 2012, the U.S. Food and Drug Administration granted regular
      approval of imatinib mesylate tablets (Gleevec(r); Novartis Pharmaceuticals
      Corporation, East Hanover, NJ) for the adjuvant treatment of adult patients
      following complete gross resection of Kit(+) (CD117(+)) gastrointestinal stromal
      tumors (GISTs). The recommended dose of imatinib is 400 mg/day administered daily
      for 3 years. Three hundred ninety-seven patients were enrolled in a randomized
      adjuvant, multicenter, open label, phase III trial comparing 12 months with 36
      months of imatinib treatment. Eligible patients had one of the following: tumor
      diameter >5 cm and mitotic count >5 per 50 high power fields (HPFs); tumor
      diameter >10 cm and any mitotic count; tumor of any size with mitotic count
      >10/50 HPFs; or tumor ruptured into the peritoneal cavity. The primary endpoint
      was the recurrence-free survival (RFS) interval. The median follow-up for
      patients without an RFS event was 42 months. There were 84 (42%) RFS events in
      the 12-month treatment arm and 50 (25%) RFS events in the 36-month treatment arm.
      Thirty-six months of imatinib treatment led to a significantly longer RFS
      interval than with 12 months of treatment. The median follow-up for overall
      survival (OS) evaluation in patients still living was 48 months. Thirty-six
      months of imatinib treatment led to a significantly longer OS time than with 12
      months of imatinib treatment. The most common adverse reactions, as noted in
      previous imatinib studies, were diarrhea, fatigue, nausea, edema, decreased
      hemoglobin, rash, vomiting, and abdominal pain.

PMID- 22643538
TI  - Circulating tumor cell count is a prognostic factor in metastatic colorectal
      cancer patients receiving first-line chemotherapy plus bevacizumab: a Spanish
      Cooperative Group for the Treatment of Digestive Tumors study.
AB  - BACKGROUND: The Maintenance in Colorectal Cancer trial was a phase III study to
      assess maintenance therapy with single-agent bevacizumab versus bevacizumab plus
      chemotherapy in patients with metastatic colorectal cancer. An ancillary study
      was conducted to evaluate the circulating tumor cell (CTC) count as a prognostic
      and/or predictive marker for efficacy endpoints. PATIENTS AND METHODS: One
      hundred eighty patients were included. Blood samples were obtained at baseline
      and after three cycles. CTC enumeration was carried out using the CellSearch(r)
      System (Veridex LLC, Raritan, NJ). Computed tomography scans were performed at
      cycle 3 and 6 and every 12 weeks thereafter for tumor response assessment.
      RESULTS: The median progression-free survival (PFS) interval for patients with a
      CTC count >=3 at baseline was 7.8 months, versus the 12.0 months achieved by
      patients with a CTC count <3 (p = .0002). The median overall survival (OS) time
      was 17.7 months for patients with a CTC count >=3, compared with 25.1 months for
      patients with a lower count (p = .0059). After three cycles, the median PFS
      interval for patients with a low CTC count was 10.8 months, significantly longer
      than the 7.5 months for patients with a high CTC count (p = .005). The median OS
      time for patients with a CTC count <3 was significantly longer than for patients
      with a CTC count >=3, 25.1 months versus 16.2 months, respectively (p = .0095).
      CONCLUSIONS: The CTC count is a strong prognostic factor for PFS and OS outcomes
      in metastatic colorectal cancer patients.

PMID- 22643541
TI  - Neuromonitoring in traumatic brain injury.
AB  - Current approaches to monitoring in severe traumatic brain injury (TBI) include a
      wide array of modalities, providing insight into pressure parameters,
      oxygenation, perfusion, electrophysiology and metabolism of the brain. The intent
      of "multimodality monitoring" is to obtain a better understanding of what is
      going on within the brain of an individual patient in order to target treatment
      more appropriately. In this review we highlight the current status of
      neuromonitoring for TBI with a specific focus on how advanced analysis and
      integration of these parameters may be used to implement more personalized
      treatment approaches. In particular, combining information from different
      parameters and performing dynamic testing offers the potential to better
      understand the pathophysiological mechanisms active in the brain of a particular
      patient. Rather than persisting in a standardized "one size fits all" approach to
      therapy or continuing down the separate tracts of goal directed therapy, we
      suggest to think more in terms of "individualized therapeutic strategies" more
      focused on the specific requirements of each patient. Given the considerable data
      overload in multimodality monitoring and the complexity in interpretation of
      signals from multiple sources, specific attention needs to be directed to data
      processing and user-friendly displays. Intense collaboration and interaction
      between clinicians, basic researchers, IT-experts, nurses and industry will be
      required to further advance the fields towards more personalized approaches.

PMID- 22643539
TI  - Airway management in pediatric patients using the Glidescope Cobalt(r): a
      feasibility study.
AB  - BACKGROUND: Video laryngoscopes are claimed to improve airway management. Several
      studies showed an equal or better glottic view using the Glidescope(r) compared
      with direct laryngoscopy in adults and in paediatric patients. Many case reports
      also described successful intubation in patients with a difficult airway. The
      Glidescope Cobalt(r) is a modified Glidescope(r) with a disposable sheath. Data
      on clinical application in paediatric patients is insufficient. METHODS: Twenty
      four pediatric patients with a mean age of 27 months [range, 1-142] undergoing
      general anesthesia were included into this feasibility study. Cormack and Lehane
      grade was evaluated using a Macintosh blade. Tracheal intubation was performed
      using the Glidescope Cobalt(r). Number of attempts, time to intubation, Cormack
      and Lehane (C&L) grade and a subjective score were noted for both a resident and
      an attending anesthesiologist. RESULTS: With the Glidescope Cobalt(r) the C&L
      grade improved in all patients with grade 2 or 3 to 1 and deteriorated in one
      case from C&L grade 1 to 2. The C&L grade remained unchanged in 15 patients
      (62.5%). C&L grades between resident and attending anesthesiologist were equal.
      Tracheal intubation was successful in 92% with a stylet-armed tube and in 8%
      using an unarmed tube with a Magill forceps, respectively. Time to intubation was
      median 50.5 [range, 22-93] seconds. CONCLUSION: The Glidescope Cobalt(r)
      presented suitable for use in children. C&L grade was significantly improved in
      all patients with a C&L grade of 2 or 3. Especially for educational purposes in
      pediatric anesthesia it provides a good view for all participants.

PMID- 22643542
TI  - Severe chest and back pain and bilateral massive adrenal swelling in polycythemia
      vera: an uncommon case after esophagectomy.

PMID- 22643543
TI  - Back to the bench: inhaled iloprost and prone positioning in ARDS.

PMID- 22643548
TI  - Issue overview.

PMID- 22643549
TI  - The utility of large coalitions for community health programs.

PMID- 22643551
TI  - Using mini-grants and service-learning projects to prepare students to serve
      underserved populations.
AB  - This article discusses a short term service-learning initiative developed by the
      Center for Community Health and Service Learning (CCHSL) at Morehouse School of
      Medicine, exploring how extramural mini-grant opportunities can be used to teach
      students and residents about community health assessment, health communication,
      and health promotion.

PMID- 22643550
TI  - Paths to success: optimal and equitable health outcomes for all.
AB  - Abstract:U.S. health disparities are real, pervasive, and persistent,     despite
      dramatic improvements in civil rights and economic opportunity     for racial and
      ethnic minority and lower socioeconomic groups in the     United States. Change
      is possible, however. Disparities vary widely     from one community to another,
      suggesting that they are not inevitable.     Some communities even show
      paradoxically good outcomes and relative     health equity despite significant
      social inequities. A few communities     have even improved from high disparities
      to more equitable and optimal     health outcomes. These positive-deviance
      communities show that     disparities can be overcome and that health equity is
      achievable.     Research must shift from defining the problem (including causes
      and     risk factors) to testing effective interventions, informed by the    
      natural experiments of what has worked in communities that are already     moving
      toward health equity. At the local level, we need     multi-dimensional
      interventions designed in partnership with     communities and continuously
      improved by rapid-cycle surveillance     feedback loops of community-level
      disparities metrics. Similarly     coordinated strategies are needed at state and
      national levels to take     success to scale. We propose ten specific steps to
      follow on a health     equity path toward optimal and equitable health outcomes
      for all     Americans.

PMID- 22643552
TI  - Developing health leaders to combat sexual health disparities.
AB  - Health disparities, including sexual health disparities, remain pervasive in our
      society. The Satcher Health Leadership Institute at Morehouse School of Medicine,
      through its Sexual Health Scholars and Health Policy Leadership Fellowship
      Programs, is preparing the next generation of health leaders with the necessary
      knowledge and skills to combat health disparities.

PMID- 22643553
TI  - Using evaluability assessment and evaluation capacity-building to strengthen
      community-based prevention initiatives.
AB  - OBJECTIVES: To examine the process of community-campus engagement in an
      initiative developed to build evaluation capacities of community-based
      organizations (CBOs). METHODS: Evaluability assessment, capacity-building, self
      administered surveys and semi-structured interviews were conducted from 2004 to
      2007 and analyzed through transcript assessment and SPSS to identify trends,
      relationships and capacity changes over time. RESULTS: Evaluability assessment
      identified CBO strengths in program planning and implementation and challenges in
      measurable objective development, systematic use of mixed methods, data
      management and analysis. Evaluability assessment informed evaluation capacity
      building (ECB) trainings, teleconferences and webinars that resulted in
      statistically significant improvements in evaluation knowledge, skills, and
      abilities. Post-initiative interviews indicated CBO preferences for face-to-face
      training in logic model development, mixed method data collection and analysis.
      CONCLUSION: This report illustrates the use of mixed methods to plan, implement
      and evaluate a model to catalyze CBOs systematic assessment of prevention
      initiatives and considerations in evaluation capacity-building.

PMID- 22643554
TI  - The Southeastern U.S. Collaborative Center of Excellence in the Elimination of
      Disparities (SUCCEED): reducing breast and cervical cancer disparities for
      African American women.
AB  - This supplement highlights the efforts of Morehouse School of Medicine's
      Prevention Research Center and its partners to reduce the disparities experienced
      by African American women for breast and cervical cancer in Georgia, North
      Carolina and South Carolina. The project (entitled the Southeastern U.S.
      Collaborative CEED, or SUCCEED) is supported by a Centers for Disease Control and
      Prevention (CDC) grant to establish a Center of Excellence in the Elimination of
      Disparities (CEED). This introductory paper provides an overview describing the
      project's goals and core components and closes by introducing the adjoining
      papers that describe in more detail these components. The program components for
      SUCCEED include providing training and technical assistance for implementing
      evidence-based interventions for breast and cervical cancer; supporting capacity
      building and sustainability efforts for community-based organizations; promoting
      the establishment of new empowered community coalitions and providing advocacy
      training to cancer advocates in order to affect health systems and policies.

PMID- 22643555
TI  - The SUCCEED Legacy Grant program: enhancing community capacity to implement
      evidence-based interventions in breast and cervical cancer.
AB  - The Southeastern U.S. Collaborative Center of Excellence in the Elimination of
      Disparities Legacy Grant Program provides funding to increase community-based
      organizations' capacity to implement evidence-based breast and cervical cancer
      interventions for African American women. This article describes the development
      of the grant process, summarizes Legacy grantee outcomes, and discusses lessons
      learned.

PMID- 22643556
TI  - Removing obstacles one patient at a time: the importance of faith based health
      care in the community.
AB  - Samaritan Clinic, a faith-based, safety-net clinic in Albany, Georgia is an
      outreach ministry of Mt. Zion and Second Mt. Zion Baptist Church. Through
      volunteerism, Samaritan Clinic has served 3,335 patients representing 7,092
      visits; this is a story of faith made possible by a grant to Samaritan Clinic
      from Morehouse School of Medicine.

PMID- 22643557
TI  - USPSTF screening recommendations for breast cancer: the potential impact on the
      African American community.
AB  - African American women are more often diagnosed with breast cancer at ages
      younger than 50, have lower mammography screening rates, have higher breast
      cancer mortality rates, and more advanced stage at breast tumor diagnoses, than
      other women. Early detection through mammography screening is important in
      decreasing mortality. The revised United States Preventive Services Task Force
      (USPSTF) breast cancer screening guidelines, however, make no recommendation for
      routine mammography screening in women aged 40-49 years. Given the well
      documented disparities experienced by several underrepresented populations,
      especially African American women, this recommendation has raised concerns among
      the public and medical community. The 2009 USPSTF breast cancer screening
      guidelines should be modified to take into account populations with different
      profiles that put them at higher risk. This commentary describes the burden of
      breast cancer among African American women and identifies issues with the current
      USPSTF guidelines that have the potential to uniquely impact African American
      women and increase breast cancer disparities. This commentary concludes with
      recommendations for future directions.

PMID- 22643558
TI  - A comparison of breast and cervical cancer legislation and screening in Georgia,
      North Carolina, and South Carolina.
AB  - We identified legislation (1989-2005) relating to breast and cervical cancer in
      Georgia, North Carolina, and South Carolina and examined its impact on screening
      rates for these cancers and on Black-White disparities in screening rates.
      Legislation was identified using the National Cancer Institute's (NCI) State
      Cancer Legislative Database (SCLD) Program. Screening rates were identified using
      the Centers for Disease Control and Prevention's Behavioral Risk Factor
      Surveillance System. Georgia and North Carolina enacted more laws on breast and
      cervical cancer than did South Carolina. The laws specifically intended to
      increase breast and cervical cancer screening were mandates requiring that
      insurance policies cover such screening; Georgia and North Carolina enacted such
      laws, but South Carolina did not. However, we were unable to demonstrate an
      effect of these laws on either screening rates or disparities. This may reinforce
      the importance of evidence-based health promotion programs to increase screening.

PMID- 22643559
TI  - A community-academic partnership to plan and implement an evidence-based lay
      health advisor program for promoting breast cancer screening.
AB  - Despite a growing body of evidence concerning effective approaches to increasing
      breast cancer screening, the gap between research and practice continues. The
      North Carolina Breast Cancer Screening Program (NC-BCSP) is an example of an
      evidence-based intervention that uses trained lay health advisors (LHA) to
      promote breast cancer screening. Partnerships that link academic researchers
      knowledgeable about specific evidence-based programs with community-based
      practitioners offer a model for increasing their use. This article describes a
      partnership between CrossWorks, Inc., a community-based organization, and the UNC
      CH Lineberger Comprehensive Cancer Center in planning and implementing an
      evidence-based program for promoting breast cancer screening among older African
      American women in rural eastern North Carolina communities. We used in-depth
      interviews to explore the relationship of the partnership to the activities that
      were undertaken to launch the evidence-based program.

PMID- 22643560
TI  - Bevacizumab and erlotinib in previously untreated inoperable and metastatic
      hepatocellular carcinoma.
AB  - PURPOSE: To evaluate the combination of erlotinib and bevacizumab in subjects
      with hepatocellular carcinoma (HCC) who are not candidates for local therapy.
      PATIENTS AND METHODS: Twenty-one subjects with metastatic or inoperable HCC who
      had not received local or systemic therapy were treated with 15 mg/kg bevacizumab
      every 3 weeks and a daily dose of 150 mg oral erlotinib. The primary endpoint was
      progression-free survival (PFS) at 27 weeks. The secondary endpoints were median
      time to progression and median overall survival. RESULTS: Twenty-one subjects
      were enrolled. Eighteen were evaluable for the primary endpoint; all subjects
      were evaluable for toxicity. The median age was 60 years (range, 33 to 81 y).
      Five subjects (28%) were progression free at 27 weeks (90% confidence interval
      (CI), 12%-50%). Median time to progression was 2.57 months (95% CI, 2.13-4.20
      mo). Median overall survival was 8.33 months (95% CI, 5.73-13.97 mo). Two
      subjects withdrew consent, and 1 subject did not have adequate baseline scans.
      CONCLUSIONS: The 28% progression-free survival rate at 27 weeks was not
      significantly higher than the recent historical control rate of 20% observed on
      the placebo arm of the Sorafenib Hepatocellular Carcinoma Assessment Randomized
      Protocol trial (P=0.28). The combination of bevacizumab and erlotinib does not
      appear to have sufficient efficacy in patients with unresectable and metastatic
      HCC not amenable to local therapy, and may not warrant further investigation.
      However, this could be evaluated as an alternative to those intolerant to
      sorafenib therapy.

PMID- 22643561
TI  - Quality of life, muscle strength, and fatigue perception in patients on
      suppressive therapy with levothyroxine for differentiated thyroid carcinoma.
AB  - OBJECTIVES: The aim of this study was to evaluate the fatigue perception, the
      muscle function, and the health-related quality of life (QoL) in subclinical
      hyperthyroidism (SCH) induced by levothyroxine in the treatment of differentiated
      thyroid carcinoma, in comparison with a group of euthyroid (EU) subjects.
      PATIENTS AND METHODS: A cross-sectional study with 38 SCH individuals and 54 EU
      subjects was performed. They were submitted to Short Form-36 and Chalder
      questionnaires to evaluate QoL and fatigue, respectively. The tests performed to
      evaluate muscle function of upper and lower limbs were: maximum quadriceps
      isometric strength (QS); quadriceps fatigue resistance (T50% QS), QS at 30
      seconds (QS30s); quadriceps functional capacity (QFC); maximum isometric handgrip
      strength (HS); fatigue handgrip resistance (T50% HS), HS at 30 seconds (HS30s);
      and functional capacity of the shoulder. RESULTS AND CONCLUSIONS: The SCH
      patients had worse muscle function, regarding HS (25.19 +/- 7.00 vs. 30.45 +/-
      9.98 kgf in EU, P = 0.009) and functional capacity of the shoulder (41.28 +/-
      48.36 vs. 56.68 +/- 37.44 s in EU, P = 0.004). The self-perception of fatigue by
      Chalder questionnaire (23.91 +/- 5.39 vs. 29.77 +/- 7.03, P = 0.000) and the QoL
      in terms of functional capacity (70.20 +/- 21.57 vs. 56.25 +/- 28.79, P = 0.025),
      physical aspects (71.42 +/- 36.44 vs. 45.83 +/- 42.88, P = 0.004), pain (62.48 +/
      22.20 vs. 50.05 +/- 24.80, P = 0.035), and emotional aspects (70.74 +/- 38.26
      vs. 46.29 +/- 44.56, P = 0.008) were also worse in SCH. In conclusion, the SCH
      was associated with alterations in the QoL, reduction in the muscle function of
      upper limbs, and higher degree of fatigue.

PMID- 22643562
TI  - Dose escalation of amifostine for radioprotection during pelvic accelerated
      radiotherapy.
AB  - OBJECTIVES: Experimental data suggest a dose-dependent efficacy of amifostine so
      that the low overall doses used in clinical trials may have masked the full
      potential of the drug. In this study, we report our experience with the role of
      escalated doses of amifostine in the protection of pelvic tissues. METHODS: A
      total of 354 patients with pelvic carcinomas recruited in prospective protocols
      applying hypofractionated and accelerated radiotherapy (HypoARC) supported with
      escalated daily doses of amifostine (0, 500, 750, 1000 mg subcutaneously) were
      analyzed. Conformal pelvic radiation delivered 14 daily fractions of 2.7 Gy
      within 18 days, whereas booster techniques increased the daily fraction to the
      target area to 3.4 Gy. RESULTS: Using a dose-individualization algorithm, 55.4%
      tolerated a daily amifostine dose of 1000 mg (level 3), 15.9% of 750 mg (level
      2), and 17.5% of 500 mg (level 1), whereas intolerance induced amifostine
      interruption in 11.3% of the patients. Early grade 2/3 urinary frequency and
      dysuria grades 1 to 2 were significantly higher in level 0 patients (P = 0.04 and
      0.01, respectively). The dose level (1 to 3) of amifostine did not influence the
      incidence of frequency/dysurea. Acute diarrhea and proctitis grade 2/3 were
      significantly lower only in level 3 (P < 0.0001 and 0.03, respectively). Dose
      level 3 was also linked to reduced incidence of late bladder and intestinal
      toxicities (P<0.05). Local control analysis showed no tumor protection effect of
      amifostine. CONCLUSIONS: Higher amifostine doses are tolerable by patients with
      pelvic malignancies and can better protect pelvic tissues against early and short
      term late effects of radiotherapy.

PMID- 22643563
TI  - Sexual dysfunction in female cancer survivors.
AB  - Cancer survivors face a myriad of long-term effects of their disease, diagnosis,
      and treatment, and chief among many are problems associated with sexual
      dysfunction. Yet despite their frequency and the degree of distress they cause
      patients, sexual dysfunction is not effectively screened for or treated, and this
      is particularly true in female survivors. Inconsistently performed general sexual
      health screening at all facets of cancer care and survivorship ultimately
      translates into missed attempts to identify and treat dysfunction when it does
      arise. In this paper, we will review the current research and clinical practices
      addressing sexual dysfunction in female cancer survivors and propose questions in
      need of future research attention. This article will review the phases of sexual
      response and how each may be affected by the physical and emotional stress of
      cancer diagnosis and treatment. We will then discuss existing tools for
      assessment of sexual function and approaches to their treatment. Finally, we will
      conclude with advice to health care professionals based on current research and
      suggest questions for future study. 

PMID- 22643564
TI  - Chemotherapeutic strategies in advanced or metastatic pancreatic adenocarcinoma.
AB  - Pancreatic cancer remains a formidable challenge for oncologists. The only
      curative option remains surgical resection in early-staged disease. Cytotoxic
      chemotherapy offers a modest survival benefit in the advanced or metastatic
      stage. Clinical trials of therapy have not yet yielded encouraging outcomes in
      advanced pancreatic cancer. In this review, we highlight recent developments in
      therapy focusing on trials conducted in the advanced or metastatic setting and
      offer insight into the challenges for future studies. 

PMID- 22643565
TI  - Inferior vena cava filter placement and risk of hematogenous distant metastasis
      in ovarian cancer.
AB  - BACKGROUND: Recent studies have suggested that inferior vena cava (IVC) filter
      placement in cancer patients is associated with decreased survival time after
      insertion. Causality, however, is yet to be understood. This study evaluates (i)
      the patterns of recurrence or progression of disease; and (ii) survival outcomes
      of ovarian cancer patients who underwent IVC filter placement. METHODS: A total
      of 274 patients who underwent primary cytoreductive surgery for epithelial
      ovarian, fallopian tube, and primary peritoneal cancers were identified for
      analysis. Anatomic location of the first recurrence or progression of disease,
      progression-free survival, and overall survival were correlated to IVC filter
      placement status inserted during the perioperative period. RESULTS: Overall, 38
      (13.9%) patients underwent perioperative IVC filter insertion, of which 37
      (97.4%) were permanently placed. The most common indication was newly diagnosed
      venous thromboembolism (VTE) (52.6%). Patients with IVC filter placement for VTE
      were more likely to develop subsequent deep vein thrombosis (25% vs. 7.2%, odds
      ratio, 4.31, 95% confidence interval, 1.40-13.3, P = 0.019), have hematogenous
      distant metastasis as the site of first recurrence or progression of disease (12
      mo hematogenous distant metastasis ratio, 45.2% vs. 13.6%, hazard ratio, 5.10,
      95% confidence interval, 2.35-11.1, P < 0.001, multivariate analysis), and show
      decreased survival outcomes (median progression-free survival, 5.7 vs. 15.3 mo, P
      < 0.001: and median overall survival, 22.1 vs. 47.2 mo, P = 0.002, both
      multivariate analysis) when compared with patients without IVC filter placement.
      CONCLUSIONS: Our results suggested that IVC filter placement for VTE in the
      perioperative period of primary cytoreductive surgery for ovarian cancer may be
      associated with increased risk of hematogenous distant metastasis and resulted in
      decreased survival.

PMID- 22643566
TI  - Increasing use of elective mastectomy and contralateral prophylactic surgery
      among breast conservation candidates: a 14-year report from a comprehensive
      cancer center.
AB  - BACKGROUND: First-line surgical options for early-stage breast cancer include
      breast-conserving surgery (BCS) or mastectomy. We analyzed factors that influence
      the receipt of mastectomy and resultant trends over time. METHODS: We analyzed
      the rates of mastectomy and BCS for 1634 women who underwent upfront surgical
      treatment for AJCC stage 0, I, or II breast cancer between 1995 and 2008 using
      data from the University of Louisville James Graham Brown Cancer Center Tumor
      Registry. We examined the trend of treatment over time and assessed the
      probability of receiving mastectomy using multivariate logistic regression.
      RESULTS: Overall, 65.9% of women received BCS, and 34.1% received mastectomy over
      a 14-year period (annual BCS rate range, 38.6% to 77.7%). The mastectomy rate
      substantially decreased from 43.5% in 1995 to 22.5% in 2004 (P = 0.0007) but then
      increased to 51.7% in 2008 (P < 0.0001). During the years between 2004 and 2008
      (vs. 1995 to 2003), there was a significant increase in the rates of mastectomy
      performed in conjunction with immediate reconstruction (IR: 35.7% vs. 8.4%; P <
      0.0001) and/or contralateral prophylactic mastectomy (CPM: 22.9% vs. 3.3%; P <
      0.0001). On the basis of the multivariate analysis, the rate of receiving
      mastectomy was drastically higher for patients treated since 2004 (vs. before
      2004), uninsured and government-insured (vs. privately insured) patients,
      patients with pT2 disease (vs. pTis or pT1), patients with pN1 disease (vs. pNX
      or pN0). CONCLUSIONS: In this longitudinal registry study, major independent
      determinants of mastectomy for early-stage breast cancer include year of
      diagnosis, insurance status, and stage. Mastectomy rates declined until 2004, but
      have since increased in conjunction with immediate reconstruction and
      contralateral prophylactic mastectomy. Additional study is needed to identify the
      underlying reasons for and unintended consequences of the reemergence of radical
      surgery for early-stage breast cancer in the era of multidisciplinary care.

PMID- 22643567
TI  - Factors associated with suboptimal colorectal cancer screening in US immigrants.
AB  - BACKGROUND: Our objectives were to: (1) compare colorectal cancer screening
      (CRCS) among US born citizens (USBs), naturalized citizens (NACs), and
      noncitizens (NOCs) and (2) evaluate clinical factors and potential barriers
      associated with CRCS in these populations. METHODS: Screening-eligible patients
      were identified from the 2007 California Health Interview Survey. Up-to-date CRCS
      was defined as a fecal occult blood test within 1 year, a sigmoidoscopy within 5
      years, or a colonoscopy within 10 years. Using logistic regression, we determined
      the effects of immigrant status on CRCS. Stratified analyses based on location of
      residence, health insurance status, and English proficiency were conducted.
      RESULTS: A total of 30,434 average-risk adults aged 50 years or older completed
      the survey. Only 67% of USBs, 61% of NACs, and 46% of NOCs underwent CRCS.
      Advanced age, male sex, high-income earners, nonsmokers, and those who were
      married or visited their physicians frequently were more likely to receive CRCS
      (all P < 0.05). Compared with USBs, both NACs and NOCs showed decreased odds of
      CRCS (odds ratio 0.88, 95% confidence interval, 0.74-1.06 and odds ratio 0.68,
      95% confidence interval, 0.53-0.88, respectively; P = 0.011). Stratified analyses
      revealed that the associations between immigrants and decreased CRCS were more
      prominent for those who lived in rural areas, lacked insurance, or were not
      English proficient. CONCLUSIONS: CRCS remains suboptimal, especially in new US
      immigrants. Improving health care access and mitigating language barriers may
      minimize this disparity.

PMID- 22643568
TI  - Comparing time to disease progression of irinotecan and oxaliplatin-based
      chemotherapies in colorectal cancer patients with liver only metastasis.
AB  - OBJECTIVES: The liver is the most common metastatic site in colorectal cancer
      (CRC). In this study, we evaluated if there is any difference between first-line
      irinotecan-based and oxaliplatin-based chemotherapies in the duration of time to
      disease progression (TTP) in CRC patients with only liver metastasis. METHODS: We
      retrospectively reviewed the medical records of patients with metastatic CRC
      referred to the Medical Oncology Department at the Faculty of Medicine of Ege
      University, between January 2002 and December 2010. Seventy-seven patients had
      only liver metastasis and completed their first-line chemotherapy. Forty-two
      patients had oxaliplatin-based treatments while 12 also had bevacizumab therapy,
      and 35 patients had irinotecan-based treatments while 16 also had bevacizumab
      therapy. RESULTS: Median TTP was 6.70 +/- 0.29 months for patients treated with
      oxaliplatin+5-fluorouracil (5-FU) and 8.33 +/- 1.15 months for patients treated
      with oxaliplatin+5-FU+bevacizumab. TTP was significantly improved for patients
      who received irinotecan+5-FU+bevacizumab (median TTP, 13.73 +/- 2.10 mo) when
      compared with irinotecan+5-FU (median TTP, 5.13 +/- 0.70 mo). CONCLUSIONS:
      Although previous studies showed no survival difference between these 2
      chemotherapeutic agents in metastatic CRC, there might be differences in the
      benefit of delaying the disease progression in subgroup populations. Irinotecan+5
      FU with bevacizumab combination chemotherapy may be superior in the first-line
      treatment of CRC with hepatic only metastasis.

PMID- 22643570
TI  - Bibliography. Child and adolescent psychiatry. Current world literature.

PMID- 22643569
TI  - Yttrium-90 microsphere-selective internal radiation therapy with chemotherapy
      (chemo-SIRT) for colorectal cancer liver metastases: an in vivo double-arm
      controlled phase II trial.
AB  - OBJECTIVES: Selective internal radiation therapy (SIRT) with yttrium-90 (Y)
      microspheres has emerged as an effective liver-directed therapy with a favorable
      therapeutic ratio for treatment of colorectal cancer liver metastases. The aim of
      this study was to investigate the objective responses obtained by Y microsphere
      treatment when combined with contemporary chemotherapy in the front-line (first
      or second line) setting in patients with CRCLM. METHODS: This study used an in
      vivo comparison between the right and left liver lobes; systemic chemotherapy was
      supplied to both liver lobes by virtue of systemic administration, whereas SIRT
      was administered selectively to the target liver lobe only. Response to treatment
      was evaluated by serial fludeoxyglucose positron emission tomography computed
      tomography performed at 4 weeks, 2 to 4 months, and 6 to 8 months. Standard
      uptake value, anatomic volume, functional tumor volume, and total lesion
      glycolysis (TLG) calculations were obtained at each time point. RESULTS: A
      decrease in TLG on fludeoxyglucose positron emission tomography computed
      tomography imaging was seen in 19 of the 20 patients. The mean decrease in TLG
      values in the tumors receiving chemo-SIRT and chemo-only treatment were 86.26%+/
      18.57% and 31.74%+/-80.99% (P<0.01), 93.13%+/-11.81% and 40.80%+/-73.32%
      (P=0.01), and 90.55%+/-19.75% and 54.91%+/-38.55% (P<0.01) at 4 weeks, 2 to 4
      months, 6 to 8 months posttreatment, respectively. Functional and anatomic tumor
      volume changes were in concordance with the TLG changes. CONCLUSIONS: The study
      demonstrated that, under near identical conditions in terms of patient and tumor
      characteristics, the chemo-SIRT combination produced superior objective responses
      compared with chemo-only treatment in a front-line treatment setting in patients
      with colorectal cancer liver metastases.

PMID- 22643572
TI  - Effect of gait speed on muscle activity patterns and magnitude during stance.
AB  - This study aims to assess the influence of gait speed (manipulated through
      cadence) on muscle activity patterns and activation degree during stance.
      METHODS: Thirty-five healthy individuals participated in this study. Surface
      electromyographic activity from the gastrocnemius medialis (GM), gluteus maximus
      (GMax), biceps femoris (BF) and rectus femoris (RF) was acquired with subjects
      walking at three different speeds. RESULTS: Speed influenced: (1) relative motor
      activity patterns at heel strike, midstance-propulsion transition and propulsion;
      (2) the activity level of RF, GMax, GM and BF, in decreasing order, with higher
      activity at the fastest and slowest speeds. CONCLUSIONS: In general, muscle
      activity was higher at the fastest and slowest speeds than at the self-selected
      speed and only the activity of the main actions in each subphase remained stable.
      These findings suggest that gait speeds different from the self-selected speed
      influence not only activity levels but also relative muscle activity patterns. As
      a result, caution is advised when choosing standard speeds in gait studies, as
      this can lead to increased variability in relative muscle activity patterns.

PMID- 22643573
TI  - New azaspiracids in Amphidomataceae (Dinophyceae).
AB  - Azaspiracids (AZAs) are a group of lipophilic polyether toxins implicated in
      incidents of shellfish poisoning in humans, particularly in northern Europe,
      which are produced by the small marine dinoflagellate Azadinium spinosum. Other
      related species/strains of the Amphidomataceae have not been proven to date to
      contain any of the known azaspiracids. Closer analyses of these species/strains
      by triple quadrupole mass spectrometry in the precursor and product ion mode now
      revealed four new compounds with high similarity to azaspiracids, all of them
      with a characteristic m/z 348 fragment but with absence of the m/z 362 fragment.
      These compounds were detected in three species/strains, i.e. in North Sea
      isolates of Azadinium poporum (molecular mass: 845.5 Da), in a Korean isolate
      which has been designated as A. cf. poporum (molecular mass: 857.5 Da) and in
      Amphidoma languida isolated from Bantry Bay, Ireland (molecular masses: 815.5 and
      829.5 Da). Cell quotas of roughly 2-20 fg per cell were in the same range as
      found for AZA-1/-2 in A. spinosum. Structures for all compounds were proposed by
      interpretation of fragmentation patterns and high resolution mass measurements
      using Fourier transform ion cyclotron resonance-mass spectrometry (FTICR-MS).

PMID- 22643574
TI  - Pediatric hyperbaric oxygen therapy in Victoria, 1998-2010.
AB  - OBJECTIVES: The aim of this review is to identify clinical conditions currently
      treated in a pediatric population referred to the Alfred hyperbaric unit, to
      describe outcomes, and detail any complications occurring during treatment or
      transfer between units. DESIGN: Retrospective, noncontrolled, clinical study.
      SETTING: Adult hyperbaric unit in a university hospital. PATIENTS: Children aged
      <16 yrs referred for hyperbaric oxygen therapy between January 1998 and December
      2010. INTERVENTIONS: Hyperbaric oxygen therapy at pressures from 2.0 to 3.0
      atmospheres absolute. MEASUREMENTS AND MAIN RESULTS: Fifty-four patients with a
      median age at presentation of 15 yrs (range, 0.25-16 yrs) received 668 treatment
      sessions (mean, 12.4; 95% confidence interval, 9.2-15.5). Fourteen patients were
      identified as having successfully completed treatment while managed in intensive
      care units. There were 44 events in 668 treatments (6.6%) in the pediatric group
      and 12 events in 126 treatments (9.6%) in the pediatric intensive care unit
      group. There were two oxygen toxicity convulsion (0.3%), two episodes of
      progressive hypoxemia (0.3%), and four episodes of brief hypotension (0.6%).
      CONCLUSIONS: Provision of hyperbaric oxygen to children with significant illness
      is feasible and associated with a low risk of complications. The most difficult
      aspect of managing pediatric hyperbaric oxygen therapy is in the coordination of
      the treatment with ongoing surgical and intensive care management. The lack of
      pediatric staff and facilities in major hyperbaric units necessitates multiple
      transfers for appropriate treatment.

PMID- 22643575
TI  - Photophysical and electrochemical properties of platinum(II) complexes bearing a
      chromophore-acceptor dyad and their photocatalytic hydrogen evolution.
AB  - A series of platinum(II) complexes bearing a chromophore-acceptor dyad obtained
      by reacting 4-(p-bromomethylphenyl)-6-phenyl-2,2'-bipyridine or 4'-(p
      bromomethylphenyl)-2,2':6',2''-terpyridine with pyridine, 4-phenylpyridine, 4,4'
      bipyridine, 1-methyl-4-(pyridin-4'-yl)pyridinium hexafluorophosphate
      respectively, were synthesized. Their photophysical properties, emission
      quenching studies by Pt nanoparticles and methyl viologen, electrochemical
      properties and photoinduced electron-transfer reactions in a photocatalytic
      hydrogen-generating system containing triethanolamine and colloidal Pt without an
      extra electron relay, were investigated. A comparison of the rates of hydrogen
      production for the two photocatalytic systems, one containing a metal-organic
      dyad and the other comprising a 1:1 mixture of the parental platinum(II)
      complexes and the corresponding electron relay, showed that intramolecular
      electron transfer improves the photocatalytic efficiency. Compared with
      cyclometalated platinum(II) complexes, the related platinum(II) terpyridyl
      complexes exhibited poor performance for photocatalytic hydrogen evolution. An
      investigation into the amount of hydrogen generated by three platinum(II)
      complexes containing cyclometalated ligands with methyl groups located on
      different phenyl rings revealed that the efficiency of hydrogen evolution was
      affected by a subtle change of functional group on ligand, and the hydrogen
      generating efficiency in the presence or absence of methyl viologen is
      comparable, indicating electron transfer from the excited [Pt(C^N^N)] chromophore
      to colloidal Pt. (1)H NMR spectroscopy of the metal-organic dyads in an aqueous
      solution in the presence of excess triethanolamine revealed that the dyad with a
      viologen unit was unstable, and a chemical reaction in the compound occurred
      prior to irradiation by visible light under basic conditions.

PMID- 22643593
TI  - Evidence-based management of ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory disorder of the
      gastrointestinal tract, the exact etiology of which remains unknown. The
      prevalence in the general population is around 0.25%, and the condition
      represents a considerable financial burden to the health service. The natural
      history of the condition is one of periods of remission, punctuated by relapses
      of disease activity. Medical therapy aims to minimise the frequency of these
      relapses, as well as the need for glucocorticosteroids, which have potentially
      deleterious effects. In those with acute severe disease, however,
      glucocorticosteroids are probably effective, as are infliximab and cyclosporine.
      In those with a mild to moderate flare of disease activity, oral or topical 5
      ASAs, or in combination, are more effective than placebo for induction of
      remission. Doses of oral 5-ASAs in excess of 2g/day appear to lead to higher
      likelihood of successful remission. Once remission has been achieved, there is
      evidence to support the use of oral or topical 5-ASAs, and azathioprine to
      prevent relapse of disease activity. Again, doses of 5-ASA in excess of 2g/day
      are associated with a lower risk of relapse. Individuals with chronic relapsing
      and remitting disease activity are difficult to manage, and may require colectomy
      with ileal pouch anal anastamosis. Granulocyte/monocyte adsorptive apheresis
      could be of benefit in this setting, but most trials have been conducted in the
      Far East, so the efficacy in Western UC patients is unclear.

PMID- 22643594
TI  - Maximizing the effect of biologics in inflammatory bowel disease.
AB  - The chronic course of inflammatory bowel disease (IBD) leads to recurrent
      episodes of active clinical symptoms, as well as long term complications,
      including hospitalizations, surgeries, and a decreased quality of life. Biologic
      agents have been shown to be effective for the induction and maintenance of
      remission in patients with moderate to severe IBD, and may alter the natural
      history of disease. Loss of response to biologic therapy is a common problem in
      clinical practice, the reasons for which are likely multifactorial; antibody
      development, alterations in drug clearance, and possibly a change to a non-TNF
      driven inflammatory mechanism. Several studies have evaluated interventions that
      may lead to an increased rate of response and an increase in the durability. In
      this review, we evaluate ways to maximize anti-TNF treatment by administering
      scheduled therapy, using concomitant immunomodulator therapy, escalating dosage,
      and switching between biologic agents and classes. Finally, the role of antibody
      to infliximab (ATI) and infliximab serum trough levels are discussed in the
      context of optimizing biologic therapy for inflammatory bowel disease.

PMID- 22643595
TI  - Diagnosis and management of Crohn's disease of the ileal pouch.
AB  - Approximately 20-30% of patients with ulcerative colitis would eventually require
      surgery despite recent advances in medical therapy. Ileal pouch-anal anastomosis
      has become the surgical treatment of choice after total proctocolectomy. A subset
      of patients who had a preoperative diagnosis of ulcerative colitis may develop
      Crohn's disease or a Crohn's disease-like condition of the ileal pouch after
      surgery. Diagnosis, differential diagnosis, and management of Crohn's disease of
      the ileal pouch have been challenging. A combined approach with the assessment of
      clinical history, endoscopy, histology, abdominal/pelvic imaging, and examination
      under anesthesia is necessary for an accurate diagnosis, disease classification,
      management and improvement in outcome. A multidisciplinary approach with
      gastroenterologists, colorectal surgeons, gastrointestinal pathologists and
      radiologists for proper medical, endoscopic, and surgical treatment is advocated.

PMID- 22643596
TI  - Is pediatric IBD treatment different than in adults?
AB  - The incidence of pediatric inflammatory bowel disease (IBD) continues to rise in
      most countries. Approximately 20-25% of IBD patients present before the age of
      20, and their management is associated with many unique challenges. These
      challenges stem both from the inherent differences between children and adults,
      and from the differences in the nature and course of the disease. Children with
      IBD are more likely than adults to present with extensive disease - both in
      Crohn's disease (CD) and ulcerative colitis (UC). Diagnosis requires a high index
      of suspicion, as children may present with less typical signs such as poor growth
      and delayed puberty. In the very young patients with inflammatory bowel disease,
      the pediatric clinician must consider a broader range of immunological and
      allergic disorders. Optimal management requires recognition of pediatric patterns
      of presentation, efficacy and adverse-effect profiles, and understanding
      monitoring aspects unique to pediatrics. These aspects include pediatric disease
      related psychological issues, adherence to therapy and transition to adult care.
      Inadequate attention to growth, puberty or bone health in childhood can result in
      long-term consequences, such as impaired adult height and increased risk of
      fractures. Management of pediatric IBD and prevention of adverse long-term
      consequences relies on a variety of therapies well-known to the adult
      practitioner, along with therapies that are not widespread in adults, most
      notably exclusive enteral nutrition (EEN). The latter is as effective as
      corticosteroids in achieving clinical remission in children, while achieving
      better results than corticosteroids with regard to mucosal healing and growth.
      This review discusses the broad variety of issues that form the basis for
      management of pediatric IBD.

PMID- 22643597
TI  - [Autoimmune pancreatitis today: clinical features and diagnostic strategies].
AB  - Autoimmune pancreatitis (AIP) is a particular form of chronic pancreatitis
      recognized as clinical entity only in recent decades. Peculiar clinical,
      serological, histological and radiological features make it different from other
      types of pancreatitis. The diagnosis of AIP represents a challenge for the
      clinicians. Particularly in its focal form, it shows several features in common
      with pancreatic adenocarcinoma. Both of these conditions, in fact, are often
      associated with obstructive jaundice, cause increase of the volume of the
      pancreas and can share the radiologic appearance of a focal mass. The autoimmune
      pancreatitis instead of pancreatic cancer regresses promptly after treatment with
      oral corticosteroids. Because of the different management of the two diseases a
      correct differential diagnosis is imperative. From 5% to 21% of AIP cases are
      diagnosed in patients after pancreatic resection performed for suspected
      malignancy. Still not identified a specific serological marker of AIP which can
      allow a definitive diagnosis of the disease. Both the diagnosis of pancreatic
      cancer as AIP is paid on the basis of different clinical tests: the diagnosis of
      pancreatic cancer requires imaging studies, laboratory tests and biopsy of the
      pancreas, while the diagnosis of AIP requires confirmation of the diagnostic
      histological, serological and radiological criteria, the involvement of other
      organs and a positive response to treatment with corticosteroids. Recently, three
      different diagnostic strategies for AIP have been proposed.

PMID- 22643598
TI  - Hepatitis B vaccine: prophylactic, therapeutic, and diagnostic dilemma.
AB  - Hepatitis B virus (HBV) remains a serious public health problem worldwide,
      accounting for high morbidity and mortality rates as well as significant
      personal, societal, and economic costs. Hepatitis B is a preventable disease; a
      safe and effective vaccine has been available for 30 years. The World Health
      Organization aims to control HBV worldwide by integrating HB vaccination into
      infant, possibly adolescent, and at-risk adult routine immunization programs. In
      recent years, a drastic reduction in the mortality and morbidity of chronic HBV,
      including hepatocellular carcinoma, has occurred, particularly in hyperendemic
      areas. In addition, a therapeutic vaccine that enhances patient immune response
      has been considered as a possible alternative to antiviral agents. However,
      mutant HBV may infect individuals who are anti-HBs positive after immunization
      (vaccine-escape) and/or fail for detection of HBsAg (diagnostic-escape), which
      may lead to transmission through donated blood or organs. This review attempts to
      summarize the prophylactic, therapeutic, and diagnostic concerns on HBV vaccines.

PMID- 22643599
TI  - H. pylori infection and insulin resistance: the other side of the coin.

PMID- 22643601
TI  - Addressing hepatitis B: community health centers, partnerships and the Affordable
      Care Act.

PMID- 22643600
TI  - Identification of and beliefs about depressive symptoms and preferred treatment
      approaches among community-living older African Americans.
AB  - OBJECTIVE: To examine older African American's recognition of and beliefs about
      depressive symptoms, preferred symptom management strategies, and factors
      associated with willingness to use mental health treatments. Differences between
      the depressed and nondepressed and men and women were examined. DESIGN: Cross
      sectional survey. SETTING: Home, senior center. PARTICIPANTS: A total of 153
      senior center members (56 male, 97 female) 55 years and older. MEASUREMENTS:
      Using a depression vignette, participants indicated if the person was depressed
      and their endorsement of items reflecting beliefs, stigma, symptom management,
      and willingness to use treatments (yes/no). A 9-item Patient Health Questionnaire
      assessed current symptomatology. RESULTS: Overall, 24.2% reported depressive
      symptoms (>=5); 88.2% correctly identified the person in the vignette as
      depressed. Most (>=75%) endorsed active symptom management strategies, preference
      for treatment in physician and therapist offices, and willingness to take
      medications, seek therapy, see doctor, and attend support groups; less than 33%
      viewed depression as stigmatizing, whereas 48% viewed depression as normal aging.
      Logistic regressions revealed lower education, higher physical function, and
      feeling okay if community knew of depression diagnosis were associated with
      willingness to see physician if feeling depressed; being married and believing
      antidepressant medications are beneficial were related to willingness to use
      medications. Different associations emerged for depressed/nondepressed and men
      and women. CONCLUSIONS: Overall, this older African American sample had positive
      attitudes and beliefs and endorsed traditional treatment modalities suggesting
      that beliefs alone are unlikely barriers to underutilization of mental health
      services. Because different factors were associated with willingness to seek
      physician help and use medications and factors differed for
      depressed/nondepressed and by sex, interventions should be tailored.

PMID- 22643602
TI  - Prevalence of autism spectrum disorder among Nigerian children with intellectual
      disability: a stopgap assessment.
AB  - The prevalence of autism spectrum disorder (ASD) among sub-Saharan African
      children with intellectual disability is about 0.7% more than three decades ago.
      During this period, the prevalence of ASD has been on the increase worldwide.
      Studies are not available in recent times addressing epidemiology of ASD among
      sub-Saharan African children. The present study assessed the prevalence of ASD
      among Nigerian children with intellectual disability. Forty four children with
      intellectual disability were assessed for diagnosis of childhood autism based on
      criteria specified in F84.0 section of International Classification of Diseases,
      Tenth Edition (ICD-10) Diagnostic Criteria for Research. Five (11.4%) of the
      children studied met the diagnostic criteria for childhood autism. Male/female
      ratio was 4:1. There is need for large scale epidemiological studies of ASD among
      sub-Saharan African children to clearly define the inter-relationship between ASD
      and intellectual disability in this population and to help in health care policy
      formulation.

PMID- 22643603
TI  - Textmania: text messaging during the manic phase of bipolar I disorder.
AB  - Advancements in modern technology have brought tremendous changes in human
      behavior. One such change is in modes of communication such as text messaging, or
      texting. This form of communication has emerged as one of the dominant modes of
      communication in the world. This report presents a differential pattern of
      texting seen during the manic episode of a young adult with bipolar I disorder.
      We observed all the DSM IV manic symptoms; interestingly the patient's
      predominant medium for communication was texting. The patient reported a dramatic
      increase in the quantity of both texting and sex-texting (or sexting) in addition
      to a decrease in quality of the message content. In addition, there was a
      substantial increase in the number of people with whom the patient engaged in
      simultaneous texting conversations. This case provides evidence for the need to
      consider non-traditional forms of communication when evaluating a patient's
      communication pattern during mania.

PMID- 22643604
TI  - The impact of natural disaster on pediatric surgical delivery: a review of Haiti
      six months before and after the 2010 earthquake.
AB  - Little is known about pediatric surgical disease in resource-poor countries. This
      study documents the surgical care of children in central Haiti and demonstrates
      the influence of the 2010 earthquake on pediatric surgical delivery. METHODS: We
      conducted a retrospective review of operations performed at Partners in
      Health/Zanmi Lasante hospitals in central Haiti. RESULTS: Of 2,057 operations
      performed prior to the earthquake, 423 were pediatric (20.6%). Congenital
      anomalies were the most common operative indication (159/423 operations; 33.5%).
      Pediatric surgical volume increased significantly after the earthquake, with 670
      operations performed (23.0% post-earthquake v. 20.6% pre-earthquake, p=.03).
      Trauma and burns became the most common surgical diagnoses after the disaster,
      and operations for non-traumatic conditions decreased significantly (p<.01).
      CONCLUSION: Congenital anomalies represent a significant proportion of baseline
      surgical need in Haiti. A natural disaster can change the nature of pediatric
      surgical practice by significantly increasing demand for operative trauma care
      for months afterward.

PMID- 22643605
TI  - Postpartum depression: a review.
AB  - Postpartum depression is a disorder that is often unrecognized and undertreated.
      Many psychosocial stressors may have an impact on the development of postpartum
      depression. The greater risk of postpartum depression is a history of major
      depression and those who have experienced depression during past pregnancies.
      Untreated maternal depression can have a negative effect on child development,
      mother-infant bonding, and risk of anxiety or depressive symptoms in infants
      later in life. Management of postpartum depression is a vital part of adequate
      medical care. The obstetrician and pediatrician can serve important roles in
      screening for and treating postpartum depression. To prevent adverse outcomes
      associated with depression and its impact on the child, it is important that all
      health care professionals and nurse practitioners are aware of specific signs and
      symptoms, appropriate screening methods, and proper treatment. This review
      article covers major traits of postpartum depression.

PMID- 22643607
TI  - Health care of pregnant women in U.S. state prisons.
AB  - BACKGROUND: Although standards for pregnancy-related health care in correctional
      facilities have been established, there is no mandatory accreditation that
      requires adherence to these standards. Furthermore, this information has been
      difficult to access from correctional facilities across the country. METHODS: To
      examine the health care practices of pregnant women in state prisons, a survey
      with 62 multiple choice questions and four open-ended questions was developed.
      Wardens of 50 women's state correctional facilities were contacted to describe
      the study and request participation. Nineteen facilities completed the survey,
      for a 38% response rate. RESULTS: The findings of this study provide further
      evidence of the substandard care that pregnant incarcerated women receive in
      correctional facilities. In many state prisons, nutritional recommendations for a
      healthy pregnancy are not met, adequate rest is compromised and lower bunks are
      not required. Psychosocial support and education are minimal at best. The use of
      restraints, which can compromise the health and safety of the woman and her baby,
      continues as a matter of procedure in many facilities even during labor and
      delivery. CONCLUSIONS: The providers of health care for pregnant women fail to
      use best practices and established standards in many women's state prisons. A
      concerted effort is urgently needed to address the unmet health care needs of
      this marginalized population and support legislation to limit the use of
      restraints with pregnant incarcerated women in all states.

PMID- 22643606
TI  - Pain characteristics and pain catastrophizing in incarcerated women with chronic
      pain.
AB  - Chronic pain in incarcerated women is understudied and poorly described. Study
      objectives were to describe pain characteristics, correlates, and predictors in a
      convenience sample of incarcerated women with chronic pain. A survey packet that
      included the Brief Pain Inventory Short Form (BPI-SF) and the Pain
      Catastrophizing Scale (PCS) was distributed to all inmates at a state prison for
      women. Those who self-identified as having chronic pain >=4 on a 0-10 numeric
      rating scale were invited to complete the survey. Demographics and medical and
      psychiatric diagnoses were abstracted by chart review. Participants (N=159) rated
      their current and average pain intensity as severe. Pain catastrophizing was
      found to predict average pain intensity and level of pain-related interference in
      functioning. Pain catastrophizing is treatable with behavioral intervention in
      the general population. Findings suggest that pain catastrophizing may be an
      important target for research and treatment in incarcerated women with chronic
      pain.

PMID- 22643608
TI  - Social gradients in dental health among low-income mothers and their young
      children.
AB  - For low-income mothers of children aged 3-6 years, we estimate whether social
      gradients exist between mothers' income, education, and employment status and
      mothers' perceptions of self and child dental and general health, and whether
      these relationships differ by racial/ethnic group. Disproportionate stratified
      sampling by racial/ethnic group selected 10,909 eligible children aged 3 to 6 in
      Medicaid in Washington State. Mothers (n=4,373) completed a mixed-mode (web,
      mail, telephone) survey. Mothers' education had a strong, gradient relationship
      with mother ratings of self and child dental health that was not explained by
      other measures. Similar gradients were found for mothers' employment status and
      income, but some associations were no longer significant (p>.05) after adjusting
      for oral health beliefs and behaviors, dental insurance, and regular dental care.
      Associations did not differ significantly by racial/ethnic group.

PMID- 22643609
TI  - The intersection of everyday life and group prenatal care for women in two urban
      clinics.
AB  - Women from vulnerable populations encounter challenging circumstances that
      generate stress and may adversely affect their health. Group prenatal care (GPNC)
      incorporates features that address social stressors, and has been demonstrated to
      improve pregnancy outcomes and prenatal care experiences. In this qualitative
      study, we describe the complex circumstances in the lives of women receiving care
      in two urban clinics and how GPNC attenuated them. Stressors included problems
      with transportation and child care, demanding jobs, poverty, homelessness,
      difficult relationships with partners, limited family support, and frustrating
      health care experiences. Receiving prenatal care in groups allowed women to
      strengthen relationships with significant others, gain social support, and
      develop meaningful relationships with group leaders. By eliminating waits and
      providing the opportunity to participate in care, GPNC also offered sanctuary
      from frustrations encountered in receiving individual care. Reducing such
      stressors may help improve pregnancy outcomes; however, more evidence is needed
      on mechanisms underlying these effects.

PMID- 22643610
TI  - Does the epidemiologic paradox hold in the presence of risk factors for low birth
      weight infants among Mexican-born women in Colorado?
AB  - OBJECTIVES: To test whether foreign-born status confers a protective effect
      against low birth weight (LBW) outcomes among Mexican-origin women in Colorado.
      METHODS: Retrospective cohort study utilizing Colorado birth records from 1989
      2004 for multivariate logistic regression analysis. The study population was
      66,422 U.S.-born women of Mexican origin (USB) and 85,000 Mexican-born (MB) women
      with singleton births. RESULTS: Mexican-born women had 24.9% lower odds of LBW
      (OR 0.751 95% CI 0.782) than USB women. Mexican-born women had a higher
      prevalence of risk factors for LBW than their USB counterparts (anemia, cardiac
      disease, hypertension, inadequate prenatal care, less than high school
      education). After adjusting for these risk factors, MB women had 22.5% lower odds
      of having LBW infants than USB women (OR 0.775, 95% CI 0.73-0.81). CONCLUSIONS:
      This study supports the epidemiologic paradox of LBW; despite higher prevalence
      of risk factors, foreign-born status confers an overall protective effect against
      low birth weight outcomes.

PMID- 22643611
TI  - Culturally tailored health camps and cardiovascular risk among South Asian
      immigrants.
AB  - INTRODUCTION: South Asians have a high prevalence and early age of onset of
      diabetes, metabolic syndrome, and cardiovascular disease (CVD). We assess the
      potential of a culturally responsive intervention, health camps, to identify and
      inform U.S. South Asian community members at risk for CVD. METHODS: We held four
      culturally and linguistically tailored health camps between October 2009 and
      November 2010 to educate participants about and screen for CVD risk factors,
      including diabetes, hypertension, and hypercholesterolemia. Data analysis was
      conducted in December 2010. RESULTS: Nearly 300 (289) South Asians registered at
      the health camps: 20% reported a previous diagnosis of diabetes, 34% elevated
      blood pressure, and 22% hypercholesterolemia. Most (240) participants had their
      blood glucose measured; 13% had values >200 mg/dl. Most (265) had their blood
      pressure measured; 32% had elevated values. Over half (57%) of LDLs were <100
      mg/dl. DISCUSSION: Health camps are a potentially important component in
      addressing increased CVD risk in this vulnerable population.

PMID- 22643612
TI  - Low knowledge of the three-dose HPV vaccine series among mothers of rural
      Hispanic adolescents.
AB  - BACKGROUND: Few previous investigations on correlates of HPV vaccine uptake have
      included Hispanics, a group known to have a disproportionately high risk of
      cervical cancer. METHODS: Rural Hispanic mothers of daughters aged 9-17 (n=78)
      were recruited at local community events to participate in a standardized Spanish
      language survey that examined factors related to vaccine uptake. RESULTS:
      Approximately 35% of the mothers reported that their daughter had received at
      least one dose of the vaccine. Mothers who had heard of the HPV vaccine were more
      likely to have a vaccinated daughter (p<.01). Mothers who thought their
      daughter's father would approve were more likely to have a vaccinated daughter
      (p=.004). Contrary to expectation, parents who believed that only one injection
      is necessary were more likely to have a vaccinated daughter (p=.009).
      CONCLUSIONS: HPV vaccine education programs that target both parents are needed
      to ensure that Hispanic parents receive the complete HPV vaccine regimen.

PMID- 22643613
TI  - Anticipated tuberculosis stigma among health professionals and Haitian patients
      in South Florida.
AB  - This paper compares tuberculosis-related stigma perceptions of health
      professionals with that of local patient populations, and examines these in
      relation to other measures of anticipated distress. Comparison groups were
      service providers and Haitian American patients diagnosed with latent TB (LTBI).
      Providers consistently rated LTBI higher on anticipated stigma than patients both
      overall and for internal perceptions and emotions, external perceptions and
      actions, and Haitian identity. Health professionals were almost five times more
      likely than patients to report the possibility of other types of psychosocial
      distress. The findings are consistent with previous studies reporting a higher
      degree of perceived stigma among unaffected populations compared with people
      diagnosed with a medical condition. Results suggest that providers may
      overestimate the likelihood that patients with a stigmatized condition will
      experience negative consequences. This may negatively affect adherence to TB
      testing guidelines because of confidentiality concerns. The implications for
      achieving national TB elimination goals are discussed.

PMID- 22643614
TI  - Provider's perspectives on the impact of Immigration and Customs Enforcement
      (ICE) activity on immigrant health.
AB  - INTRODUCTION: Increasing Immigration and Customs Enforcement (ICE) activities
      such as raids, detention, and deportation may be affecting the health and well
      being of immigrants. This study sought to understand the impact of ICE activities
      on immigrant health from the perspective of health care providers. METHODS: An
      online survey of primary care and emergency medicine providers was conducted to
      determine whether ICE activity was negatively affecting immigrant patients.
      RESULTS: Of 327 providers surveyed, 163 responded (50%) and 156 (48%) met
      criteria for inclusion. Seventy-five (48%) of them observed negative effects of
      ICE enforcement on the health or health access of immigrant patients. Forty-three
      providers gave examples of the impact on emotional health, ability to comply with
      health care recommendations, and access. CONCLUSIONS: Health care providers are
      witnessing the negative effects of ICE activities on their immigrant patients'
      psychological and physical health. This should be considered an important
      determinant of immigrant health.

PMID- 22643616
TI  - The use of prescription medications obtained from non-medical sources among
      immigrant Latinos in the rural southeastern U.S.
AB  - We explored the relationships between behavioral, socio-cultural, and
      psychological characteristics and the use of prescription medications obtained
      from non-medical sources among predominantly Spanish-speaking Latinos in the
      rural southeastern U.S. Respondent-driven sampling (RDS) was used to identify,
      recruit, and enroll immigrant Latinos to participate in an interviewer
      administered assessment. A total of 164 respondents were interviewed in 2009.
      Average age was 34 years old, 64% of respondents were female, and nearly 85%
      reported being from Mexico. Unweighted and RDS-weighted prevalence estimates of
      any non-medical source of prescription medications were 22.6% and 15.1%,
      respectively. In multivariable modeling, respondents who perceived their
      documentation status as a barrier to health care and those with higher
      educational attainment were significantly more likely to report use of non
      medical sources. Interventions are needed to increase knowledge of eligibility to
      sources of medical care and treatment and ensure culturally congruent services
      for immigrant communities in the U.S.

PMID- 22643615
TI  - Using the Framingham Risk Score to evaluate immigrant effect on cardiovascular
      disease risk in Mexican Americans.
AB  - BACKGROUND: This study uses the Framingham Risk Score (FRS) for 10-year
      cardiovascular disease (CVD) to evaluate differences between Mexican American
      immigrants and the U.S.-born population. METHODS AND RESULTS: Data from the
      Cameron County Hispanic Cohort (N=1,559). Average total risk scores were
      generated by age group for each gender. Regression analysis was conducted
      adjusting for covariates and interaction effects. Both women and men in the CCHC
      sample who were long-term immigrant residents (mean FRS scores women 4.2 with
      p<.001 vs. men 4.0 with p<.001) or born in the U.S. (mean FRS scores women 4.6
      with p<.001 vs. men 3.3 with p<.001) had significantly higher risk scores than
      immigrants who had only been in this country for less than 10 years. The
      interaction model indicates that differences between immigrant and native-born
      Mexican Americans are most greatly felt at lowest levels of socioeconomic status
      for men in the CCHC. CONCLUSIONS: This study suggests that in terms of immigrant
      advantage in CVD risk, on whom, where, and how the comparisons are being made
      have important implications for the degree of difference observed.

PMID- 22643617
TI  - Mining for future health care providers in Appalachian Kentucky.
AB  - Recent studies project a significant shortage of U.S. health care providers
      within the next decade. To address southeastern Kentucky's persistent undersupply
      of medical professionals, a multi-county Health Career Enrichment Camp for rising
      9th and 10th grade students was implemented in 2008. This report describes the
      annual camp's development and preliminary outcomes.

PMID- 22643618
TI  - Rural medical-legal partnership and advocacy: a three-year follow-up study.
AB  - INTRODUCTION: Medical-legal partnerships perform advocacy services for vulnerable
      and underserved populations, who are burdened disproportionately by legal and
      medical problems. This study aimed to examine the effectiveness and projected
      sustainability of a rural medical-legal partnership (MLP). METHODS: Five years of
      baseline data and three years of follow-up data were analyzed using descriptive
      and inferential statistics as well as logic modeling. RESULTS: The benefit
      relative to cost of the MLP increased between the years of 2002-2006 and 2007
      2009. The number of people served increased across the two time periods, and the
      proportion of cases won remained the same. Overall, the population served
      remained similar across time. The MLP continued to show social and financial
      impacts, such as health care recovery dollars (319% return on investment between
      2007 and 2009), Social Security benefits, family law services, and end-of-life
      guidance. CONCLUSION: A rural MLP can maintain its impact and efficiency across
      time and have opportunities for expansion.

PMID- 22643619
TI  - Breast cancer mortality in Appalachia: reversing patterns of disparity over time.
AB  - Breast cancer death rates in the U.S. have decreased in recent decades, however
      areas such as Appalachia with fewer cancer care resources may not have
      experienced comparable mortality declines. This study examines trends in breast
      cancer mortality rate disparities in Appalachian states and the continental U.S.
      using data from SEER mortality files 1969-2007 and the Area Resource File.
      Overall breast cancer mortality rates decreased significantly, with a smaller
      decline in Appalachian counties (17.5%) compared with non-Appalachian counties in
      Appalachian states (30.5%), and compared with non-Appalachia U.S. counties
      (28.3%). After accounting for poverty, rural/urban status, education, health care
      resources, and proportion White in the population, residence in Appalachian
      counties except for those in the Northern subregion was significantly associated
      with smaller reduction in breast cancer mortality rates. Lower levels of
      education, physician density, and percent White in the population were also
      associated with smaller reductions in breast cancer mortality.

PMID- 22643620
TI  - Appraisal of perceived threat of diabetes and the relation to adherence for
      adults in Appalachia.
AB  - This study examined appraisal of perceived threat of diabetes and the relation to
      adherence to self-management behaviors in uninsured Appalachians receiving care
      at a free clinic. Participants were at least 18 years of age, English-speaking,
      and uninsured. Participants followed recommendations for taking prescribed oral
      medications an average of 6.6 days/week, diet 4.1 days/week, and exercise 2.9
      days/week. Relationships were found between appraisal and self-management
      variables. Diabetes was perceived more as challenging than threatening. Although
      part of a recognized group experiencing health disparities, adherence behaviors
      did not differ from those of other patient populations. Appraisal of diabetes is
      an important issue when discussing adherence with patients. Interventions
      targeting the perception of diabetes as a challenge rather than a threat would
      contribute to the understanding of adherence. Developing this characterization,
      rather than emphasizing the poor physiological outcomes associated with diabetes,
      could improve self-management behaviors and diabetes control.

PMID- 22643621
TI  - Study of a rural practice dental hygienist in a public health setting: analysis
      of an administrative dataset.
AB  - States are grappling with the lack of access to oral health care for their child
      populations. This study evaluated a unique administrative dataset collected by a
      hygienist in rural Missouri who started a new clinic and provided services to a
      two-county population under what is known as unsupervised practice. Results
      showed 82% of 2-8 year olds presenting at the clinic had no prior visits to other
      practicing dental providers, indicating the benefits of new oral health providers
      in an underserved area. School-aged children (ages 6-12 years) were significantly
      more likely than other age groups to have higher numbers of recall visits and
      therefore, subsequently to use prevention services of the unsupervised dental
      hygienist at the rural clinic. The results suggest that improved systematic
      collection of data from dental hygienists in public health settings is needed to
      provide evidence that may affect public oral health policies.

PMID- 22643622
TI  - Cancer control needs of 2-1-1 callers in Missouri, North Carolina, Texas, and
      Washington.
AB  - Innovative interventions are needed to connect underserved populations to cancer
      control services. With data from Missouri, North Carolina, Texas, and Washington
      this study a) estimated the cancer control needs of callers to 2-1-1, an
      information and referral system used by underserved populations, b) compared
      rates of need with state and national data, and c) examined receptiveness to
      needed referrals. From October 2009 to March 2010 callers' (N=1,408) cancer
      control needs were assessed in six areas: breast, cervical, and colorectal cancer
      screening, HPV vaccination, smoking, and smoke-free homes using Behavioral Risk
      Factor Surveillance System (BRFSS) survey items. Standardized estimates were
      compared with state and national rates. Nearly 70% of the sample had at least one
      cancer control need. Needs were greater for 2-1-1 callers than for state and
      national rates, and callers were receptive to referrals. 2-1-1 could be a key
      partner in efforts to reduce cancer disparities.

PMID- 22643623
TI  - Driving to better health: cancer and cardiovascular risk assessment among taxi
      cab operators in Chicago.
AB  - While a number of investigations of the health of taxi cab drivers have been
      conducted in Europe, Asia, and Africa, virtually none have been conducted in the
      United States. We undertook a survey of taxi cab operators in the Chicago area to
      understand better their health status and health promotion practices. The survey
      was completed by a convenience sample of 751 Chicago taxi drivers. Taxi drivers
      had low rates of insurance coverage, fruit and vegetable consumption, and
      physical activity compared with the general Chicago population. Participation in
      cancer screening tests was also lower for this group. A high proportion of taxi
      drivers are immigrants. They tend to be highly educated and report a readiness to
      engage in more health-promoting behaviors. Further research is needed to develop
      a targeted intervention for this population.

PMID- 22643624
TI  - Why men experiencing deep poverty in Montreal avoid using health and social
      services in times of crisis.
AB  - This article describes the experiences of men living in deep poverty regarding
      their decision not to seek out health and social services in moments of crisis,
      even when they recognized needing help. It presents results from a qualitative
      research project done in collaboration with a community center in a disadvantaged
      neighborhood of Montreal, Canada. It was designed to increase understanding of
      men's experiences of poverty and the role played by health and social services in
      their lives. Data were collected through 80 days of participant observation, 22
      semi-directed interviews, and six group discussions with men living in poverty.
      The results show that these men are reluctant to use health and social services
      for three main reasons: 1) the nature of their problems; 2) their difficulty in
      seeking help; 3) the nature of services offered. The paper concludes with
      implications of the findings for future research and interventions.

PMID- 22643625
TI  - Sociodemographic characteristics, health, and success at obtaining work among
      Latino urban day laborers.
AB  - BACKGROUND: The purpose of this study was to examine the health and social
      circumstances, knowledge of and access to health and social services, and success
      at getting work among urban day laborers. METHODS: We conducted an interview
      survey of 217 men waiting for work at several sites in San Francisco. RESULTS:
      Day laborers were generally unsuccessful at obtaining work and had less than
      optimal housing, but supported a number of family members. Over half reported
      fair or poor health, associated with longer time as a day laborer, poor English
      proficiency, and financially supporting three or more other people. Awareness of
      health and social services available to them was low. DISCUSSION: The stress of
      seeking work daily, separation from family, inadequate housing and lack of health
      care puts this population at increased risk for disease conditions associated
      with poor physical and mental health.

PMID- 22643626
TI  - Hepatitis C among clients of health care for the homeless primary care clinics.
AB  - OBJECTIVES: To describe the prevalence, distribution and risk factors for
      hepatitis C virus (HCV) infection among homeless adults using eight Health Care
      for the Homeless (HCH) clinics nationally. METHODS: Data were collected for 387
      participants through blood draws, structured interviews, chart reviews. RESULTS:
      Overall prevalence of HCV-antibody positivity was 31.0%, including 70.0% among
      injection drug users and 15.5% among reported non-injectors. Much HCV infection
      was hidden as the majority (53.3%) of HCV-antibody positive participants was
      unaware of their status. Independent risk factors for HCV among the total sample
      included injection drug use, prison, and tattoos; among injectors, risk factors
      included prison and three or more years of injection drug use; among reported non
      injectors, risk factors included tattoos and prison. CONCLUSION: These HCH
      clinics serve high concentrations of HCV-infected injectors, making these and
      similar clinics priority intervention sites for aggressive screening, education,
      testing, and treatment for HCV and other blood-borne diseases.

PMID- 22643627
TI  - Formulary expansion to provide access to medications prescribed by a specialist
      in a low-income population.
AB  - The process of expanding a medication formulary as a tool for providing access to
      medications prescribed by a specialist in a low-income population is described.
      The formulary optimized use of the 340B Drug Pricing Program and reserved patient
      assistance programs for costly medications. Collaborating with community
      physicians and organizations aided success.

PMID- 22643628
TI  - Lost in the rush to national reform: recommendations to improve impact on
      behavioral health providers in rural areas.
AB  - As the United States embarks on the most ambitious national health reform since
      the 1960s, this article highlights the challenges faced by behavioral health
      agencies, providers, and clients in rural areas and presents recommendations to
      improve access to and quality of services. Lessons learned from five years of
      research on a major systems-change initiative in New Mexico illuminate potential
      problem areas for rural agencies under national health reform, including
      insufficient financial resources, shortages of trained staff, particularly
      clinicians with advanced credentials, and delays in adopting the latest
      information technology. We recommend that rural states: (1) undertake careful
      planning for smooth transitions; (2) provide financial resources and technical
      assistance to expand rural safety-net services and capacity; (3) modify the
      health home model for the rural context; and (4) engage in ongoing evaluation,
      which can help ensure the early identification and rectification of unanticipated
      implementation issues.

PMID- 22643629
TI  - Racial disparities in intensity of care at the end-of-life: are trauma patients
      the same as the rest?
AB  - INTRODUCTION: Medicare data show Blacks and Hispanics use more health care
      resources in the last six months of life than Whites. We sought to determine if
      similar differences exist in trauma patients who died following moderate to
      severe injury. METHODS: We analyzed data from a prospective cohort study of 18
      Level 1 and 51 non-trauma centers in 12 states to examine racial/ethnic variation
      in intensity of care and hospital costs. RESULTS: Blacks were more likely than
      Whites to receive critical care consultation RR=1.67 (95% CI, 1.22, 2.30),
      specialty assessments RR=1.44 (95% CI, 1.12, 1.86) and procedures RR=1.22 (95%
      CI, 1.00, 150). Hispanics were less likely than Whites to have withdrawal-of-care
      orders, RR=0.72 (95% CI, 0.53, 0.98). CONCLUSION: Among patients who die after
      trauma, Blacks receive higher intensity of care and Hispanics were less likely to
      have withdrawal of care orders than others. This suggests racial disparities in
      patient preferences and provider treatment.

PMID- 22643630
TI  - Federally qualified health center patients and generic drug discount programs.
AB  - This study evaluates the factors associated with utilization of generic drug
      discount program (GDDP) among federally qualified health center (FQHC) patients
      in Houston, Texas. A survey to determine awareness and use of GDDP was
      administered to 304 patients at three FQHCs in Houston, Texas. Patients at FQHCs
      treated with courtesy by pharmacy staff (OR: 14.1, 95% CI: 7.9-25.2), patients
      with a perception of positive impact of GDDP on their health (OR: 7.6, 95% CI:
      4.5-12.7), those who found GDDP easy to use (OR: 6.6, 95% CI: 3.8-11.6), were
      more likely to utilize GDDP. Approximately 56% of the participants had utilized
      the GDDP at least once in the past 12 months. Approximately 85% of participants
      indicated that they would use GDDP if recommended by a physician. It is possible
      for FQHCs to be good venues for increasing awareness and utilization of GDDP.

PMID- 22643631
TI  - Implementation of Massachusetts health insurance reform with vulnerable
      populations in a safety-net setting.
AB  - This qualitative study examines the experience of racial and ethnic minorities
      receiving behavioral health care in a safety net setting during the early process
      of health insurance reform in Massachusetts. Three rounds of interviews were
      conducted between August 2007 and May 2009, collecting information from patients
      (n=65) on the experience of health reform and delivery of mental health care.
      Four categories of enrollees transitioning into health reform emerged over the
      course of the study that grouped into a typology of experiences with reform:
      early enrollees, middle enrollees, late enrollees, and multiple switchers. With
      support, a majority of the sample transitioned smoothly to the new health
      insurance mechanisms. However, some experienced administrative confusion and
      disruption in mental health care during the transition. Administrative policies
      providing special accommodations for individuals with mental health disorders and
      other vulnerable populations may be important to consider during the transition
      to health insurance reform.

PMID- 22643635
TI  - Women and children, immigrants, and rural and urban residents and health policy.
      A note from the editor.

PMID- 22643632
TI  - Awareness, treatment and control of hypertension, diabetes and hyperlipidemia and
      area-level mortality regions in the Reasons for Geographic and Racial Differences
      in Stroke (REGARDS) study.
AB  - BACKGROUND: Health Professional Shortage Areas (HPSA) receive extra federal
      resources, but recent reports suggest that HPSA may not consistently identify
      areas of need. PURPOSE: To assess areas of need based on county-level ischemic
      heart disease (IHD) and stroke mortality regions. METHODS: Need was defined by
      lack of awareness, treatment, or control of hypertension, diabetes, or
      hyperlipidemia. Counties were categorized into race-specific tertiles of IHD and
      stroke mortality using 1999-2006 CDC data. Multivariable logistic regression was
      used to model the relationships between IHD and stroke mortality region and each
      element of need. RESULTS: Awareness and treatment of cardiovascular (CVD) risk
      factors were similar for residents in counties across IHD and stroke mortality
      tertiles, but control tended to be lower in counties with the highest mortality.
      CONCLUSIONS: High stroke and IHD mortality identify distinct regions from current
      HPSA designations, and may be an additional criterion for designating areas of
      need.

PMID- 22643636
TI  - Gross nitrogen retranslocation within a canopy of Quercus serrata saplings.
AB  - Nitrogen (N) retranslocation within tree canopies has been intensively studied
      and assumed to function as a one-way process (e.g., from older to newer leaves).
      However, recent studies have found that both N output and input occur in
      individual leaves, suggesting that 'gross' N retranslocation exists behind 'net'
      N retranslocation. In the present study, the amount and direction of gross N
      retranslocation within a canopy of deciduous oak Quercus serrata Thunb. ex.
      Murray saplings were investigated. Labeling was conducted with leaves of Q.
      serrata saplings cultivated under conditions of low-N (LN) or high-N (HN)
      fertility. Subsequently, N movement within the canopy was traced. Leaves at two
      different positions in the canopy (top and lateral) were labeled to determine the
      direction of gross N retranslocation. To detect seasonal differences, the leaf
      labeling experiment was conducted twice during the early and late phases of the
      growing season. In addition, to compare the quantitative importance of gross N
      retranslocation and root N uptake, the latter was determined by labeling Q.
      serrata roots. The N-labeling experiment revealed gross N retranslocation among
      leaves, i.e., from top to lateral, lateral to top and lateral to lateral
      positions. Gross N retranslocation was quantitatively more important than root
      uptake, especially for plants cultivated at LN fertility. Season also affected
      the amount of gross N retranslocation, and these effects differed between LN and
      HN fertilities. These findings suggest that N allocation within a canopy is
      controlled dynamically by both gross N output and input. The mechanisms
      controlling gross N output and input likely function as key determinants of N
      allocation within a tree canopy.

PMID- 22643637
TI  - On the controversy of metal ion composition on amine oxygenase (AurF): a
      computational investigation.
AB  - An energetics-spectroscopic approach based on DFT method reveals that the active
      site structure of AurF has {Fe(III)(2)O} central core with one protonated
      terminal glutamate.

PMID- 22643639
TI  - Evidence that the amino acid residue Ile121 is involved in arginine kinase
      activity and structural stability.
AB  - Arginine kinase (AK) catalyzes the reversible phosphorylation of arginine by ATP,
      yielding the phosphoarginine. Domain-domain interactions may be very important to
      the structure and functions of many multidomain proteins. However, little is
      known about the role of amino acid residues located in the linker between the N-
      and C-terminal domains in the structural stability and functions of multidomain
      proteins. In this research, A series mutation of conserved residue Ile121 located
      in the linker were mutated to explore its roles in the activity and structural
      stability of AK. The mutations I121D and I121K led to pronounced loss of activity
      and structural stability. Furthermore, these mutations also led to serious
      aggregation during heat-and GdnHCl-induced denaturation and refolding from the
      GdnHCl-denatured state. More importantly, all the mutantions except I121L could
      not successfully recover their activities by dilution-initiated refolding, and
      showed significant decreased rate constant during AK refolding. While the
      mutation I121L almost had no effect on AK activity and structural stability.
      These results suggested that mutations of the residue I121 in the linker might
      affect the correct positioning of the domains and thus disrupt the efficient
      recognition and interactions between the N- and C-terminal domains.

PMID- 22643650
TI  - Comparison of pterygium recurrence rates after limbal conjunctival autograft
      transplantation and other techniques: meta-analysis.
AB  - PURPOSE: Meta-analysis to compare pterygium surgery outcomes using limbal
      conjunctival autograft (LCAG) and other techniques. METHODS: A comprehensive
      literature search was conducted through June 2011 using PubMed, Embase, and the
      Cochrane Registry to identify all randomized control trials reported so far,
      comparing the recurrence rates of pterygium after LCAG and other surgical
      techniques. The odds ratios (ORs) and 95% confidence intervals (CIs) of rates of
      pterygium recurrence were pooled using the Mantel-Haenszel method. RESULTS:
      Overall, 13 randomized control trials were included in the analysis (Jadad score,
      1-3). The pooled OR from individual studies showed that the recurrence rates
      after pterygium excision with LCAG were lower as compared with pterygium excision
      with bare sclera technique (95% CI, 0.04-0.17; pooled OR=0.08, P<0.01), bulbar
      conjunctival autograft (95% CI, 0.04-0.23; pooled OR=0.10, P<0.01), or
      intraoperative mitomycin C (95% CI, 0.09-0.52; pooled OR=0.22, P<0.01). There was
      no statistically significant difference in the recurrence rates after LCAG and
      amniotic membrane graft (95% CI, 0.26-1.70; pooled OR=0.66, P=0.39). CONCLUSIONS:
      According to the current evidence from literature, recurrence rates after
      pterygium excision with LCAG are lower when compared with the use of bare sclera,
      bulbar conjunctival autograft, or intraoperative mitomycin C. Although recurrence
      rates of LCAG were similar to the amniotic membrane graft, further large-scale
      randomized controlled trials would be required to confirm these results.

PMID- 22643638
TI  - MK-801 prevents overexpression of multidrug resistance protein 2 after status
      epilepticus.
AB  - OBJECTIVE: The aim of this study was to investigate whether NMDA receptor was
      involved in the upregulation of multidrug resistance protein 2 (Mrp2) expression
      during status epilepticus (SE). METHODS: The alterations in the expression of
      Mrp2 at various time points after  SE, and the inhibition of glutamate N-methyl-D
      aspartate (NMDA) receptor on Mrp2 expression in hippocampus were both tested by
      quantitative real-time polymerase chain reaction and western blot. Moreover,
      immunofluorescence was also used to analyze the impact of the NMDA receptor
      antagonist,  MK-801, on the distribution of Mrp2 in different brain areas.
      RESULTS: The results showed that gene encoding Mrp2 was upregulated in
      hippocampus at 6 hours after the end of SE, and this initial increase was
      followed by gradual normalization. While between 3 and 72 hours after the  end of
      SE, the protein level of Mrp2 was upregulated in hippocampus, with the highest
      level emerging at 24 hours. The increment of Mrp2 gene and protein induced by SE
      was prevented by MK-801 at 6 and 24 hours respectively after the end of SE in the
      hippocampus. Moreover, immunofluorescence  showed that seizures-induced increase
      of Mrp2 expression was attenuated by the administration of MK-801 mainly in
      capillaries. Rats after SE exhibited a significant upregulation of Mrp2 in the
      capillary endothelial cells of the cerebral cortex, piriform cortex, and
      hippocampus, compared with  those in control at 24 hours after the end of SE.
      CONCLUSION: The results indicated that the NMDA receptor plays an important role
      in the upregulation of Mrp2 expression in the blood-brain barrier.

PMID- 22643652
TI  - Who is doing mitral valve surgery in the United States?

PMID- 22643651
TI  - Reaction of carbon dioxide with a palladium-alkyl complex supported by a bis-NHC
      framework.
AB  - The reactivity of a dimethyl palladium complex supported by a dicarbene chelate
      (MDC(Mes))PdMe(2) towards CO(2) has been investigated. In the presence of trace
      H(2)O, this reaction yields the corresponding methyl bicarbonate complex
      (MDC(Mes))PdMe(O(2)COH), which goes on to give the corresponding kappa(2)
      carbonato complex upon crystallization (MDC(Mes))Pd(CO(3)). This chemistry, as
      well as related protonolysis by acetic acid was monitored by a combination of
      techniques including React-IR spectroscopy.

PMID- 22643653
TI  - The demise of the stentless valve.

PMID- 22643654
TI  - Are we ready to implant left ventricular assist devices in "less sick" patients?
AB  - Left ventricular assist devices improve survival for New York Heart Association
      class IV patients as both destination therapy and bridge-to-transplant therapy.
      This clinical benefit has been demonstrated in multiple clinical trials whose
      medical comparator arm consists of patients with very poor survival. This article
      discusses the potential use of left ventricular assist devices in a less sick
      group of patients with end-stage congestive heart failure.

PMID- 22643655
TI  - The current role of EuroSCORE.
AB  - The current status of risk modeling is briefly reviewed with emphasis on the role
      of EuroSCORE in the current era.

PMID- 22643656
TI  - The future of tissue-engineered organs for transplant? It's here!
AB  - The first-in-man bioengineered artificial tracheobronchial transplant consisting
      of a synthetic scaffold and autologous bone marrow-derived mesenchymal cells was
      recently reported. Extensive evaluation of the patient before and after
      transplant provides some insight into the potential mechanisms of stem cell
      mobilization and tracheal tissue regeneration.

PMID- 22643657
TI  - Extrapleural catheters: an effective alternative for treating postoperative pain
      for thoracic surgical patients.
AB  - Pain control is an important aspect of video-assisted thoracoscopic surgery
      (VATS) procedures. Offering an effective and low-risk method of postoperative
      pain control is thus vital to a patient's recovery. Hotta and colleagues report
      the results of a clinical study comparing efficacy of epidurals vs extrapleural
      catheters in VATS procedures. They found that extrapleural catheters provided
      equivalent postoperative pain relief when compared to thoracic epidural
      catheters.

PMID- 22643658
TI  - Surgical management of end-stage achalasia.
AB  - Esophageal achalasia is a chronic and progressive motility disorder that leads to
      massive esophageal dilation when left untreated. Treatment for achalasia is
      palliative and aimed to relieve the outflow obstruction at the level of the lower
      esophageal sphincter, yet protecting the esophageal mucosa from refluxing gastric
      acids. The best way to accomplish this goal is through an esophageal myotomy and
      partial fundoplication, with a success rate >90%. Progression of disease,
      treatment failure, and complications from gastroesophageal reflux disease cause
      progressive deterioration of the esophageal function to an end stage in about 5%
      of patients. The only chance to improve symptoms in this small group of patients
      is through an esophageal resection. This article will review the indications for
      esophagectomy in end-stage achalasia, present the different types of surgical
      approach and possibilities for reconstruction of the alimentary tract, and
      summarize the short-term and long-term postoperative results.

PMID- 22643659
TI  - Current status of lung cancer screening.
AB  - Recent results have demonstrated a major reduction in lung cancer mortality
      through computed tomography screening and no benefit from chest radiograph (CXR)
      screening. This presents a huge potential for benefit but also poses challenges
      regarding management of details to minimize harm. Many unresolved questions
      remain that must be addressed to implement computed tomography screening for lung
      cancer in a thoughtful and responsible way.

PMID- 22643660
TI  - Optimizing control of the pleural space.
AB  - Pleural space problems can create formidable treatment dilemmas for thoracic
      surgeons. Most arise as iatrogenic sequelae of lung resections, although some
      occur as late consequences of infection, hemothorax, or systemic inflammatory
      disease. Regardless of etiology, a central theme in the development and
      perpetuation of chronic pleural space problems is that there has been a loss of
      parietal-visceral pleural apposition, and this has allowed for development of an
      obligate space. A variety of surgical strategies aimed at reestablishment of
      pleural apposition and obliteration of pleural space are reviewed.

PMID- 22643661
TI  - Current role for surgery in treatment of lone atrial fibrillation.
AB  - The Cox-Maze procedure has been performed successfully since 1987. The original
      surgery was performed by using the "cut and sew" technique and is considered
      quite complex and technically demanding; therefore, it never gained popularity
      among cardiac surgeons and referring cardiologists. As surgical ablation
      technology improved, the Cox-Maze procedure can now be performed by using new
      ablation devices that deliver different energy sources (radiofrequency,
      cryothermia, and others). The use of ablation technology simplified the technical
      aspects of the procedure and has led to decreased time on cardiopulmonary bypass,
      easier placement of ablation lines, and the development of various minimally
      invasive approaches to include off-pump techniques. The Heart Rhythm Society
      recommends surgical ablation for symptomatic patients, patients who are unable to
      take anticoagulation therapy, who have failed other therapies to include
      percutaneous catheter ablation, or by personal request. Therefore, with
      guidelines in place as to patient selection and newer, easier-to-use technology,
      more surgeons are tackling surgical ablation of atrial fibrillation, offering
      another treatment option for patients with lone atrial fibrillation. This article
      will review the current state of surgery for the ablation of lone atrial
      fibrillation.

PMID- 22643662
TI  - Mitral valve surgery for dilated cardiomyopathy: current status and future roles.
AB  - There are a large number of patients with functional mitral regurgitation
      resulting from dilated cardiomyopathy. The decision between surgical correction
      and medical management of severe mitral regurgitation in heart failure can be
      difficult. The data regarding long-term benefits and mortality after surgical
      intervention are contradictory. Recent data suggest that mitral regurgitation can
      be surgically corrected in heart failure with symptomatic improvements and
      beneficial reverse remodeling. Contrary to prior beliefs, mitral valve repair can
      be performed safely with minimal postoperative mortality. Data from multi
      institutional, randomized prospective trials will help to elucidate many of the
      questions and concerns regarding repair of severe functional mitral
      regurgitation.

PMID- 22643663
TI  - Postinfarction ventricular septal defect: right ventricular approach-the extended
      "sandwich" patch.
AB  - We introduce a novel technique of ventricular septal defect (VSD) closure through
      right ventricular incision and through the VSD. It should provide extended and
      better-anchored coverage of the VSD margin and create a completely leak-free
      "sandwich" double patch by using large interrupted horizontal mattress sutures
      only, with no incision in the left ventricle wall. The patch is sutured better
      with large transseptal/transmural mattress sutures, minimizing perioperative risk
      of shunt recurrence. The second patch at the right ventricular side is easily
      placed. The patch in our method is considerably smaller than in the infarction
      exclusion technique. This method of VSD repair via right ventricular incision and
      trans-VSD approach is safe and simple, and it has so far given good, safe, and
      completely leak-free outcomes.

PMID- 22643664
TI  - Repairing the posterior postinfarction ventricular septal defect: a left
      ventricular approach with a sealant reinforced multipatch technique.
AB  - An uncommon complication of acute myocardial infarction (AMI), postinfarction
      ventricular septal defect (PI-VSD), often yields devastating outcomes. Because of
      the strikingly poor quality of the residual tissue, the repair of PI-VSD poses a
      surgical challenge and is associated with high operative mortality as well as
      residual or recurrent shunting. Among the various techniques that have been
      developed, we prefer a left ventricular approach to repairing PI-VSD by using a
      multipatch technique reinforced with a sealant as an adjunct to surgical repair.
      In this method, 3 patches are used: two overlay the left side of the VSD with a
      sealant (composed of albumin cross-linked to glutaraldehyde) sandwiched between
      them, whereas a third patch is used to cover the ventriculotomy defect. The
      rationale is that the use of such a sealant decreases the complications of PI-VSD
      repair by providing a sturdier surface for suture placement, thereby decreasing
      suture dehiscence and consequent recurrence of septal rupture. This multipatch
      technique offers hope in improving the results of the surgical management of PI
      VSD.

PMID- 22643665
TI  - Introduction: thoracoscopic mediastinal lymph node dissection for lung cancer-
      part I.

PMID- 22643666
TI  - Thoracoscopic mediastinal lymph node dissection for lung cancer.
AB  - In lung cancer, mediastinum lymphatic spread occurs. We review our technique and
      experience of thoracoscopic mediastinal lymphnode dissection (MLND). Between 1997
      and 2011, 992 patients with primary lung cancer underwent thoracoscopic major
      pulmonary resection with MLND. Initially we used a combination of electrocautery
      and clips to divide blood vessels and lymphatic channels; our current technique
      relies on a vessel sealing system (VSS) which is expeditious and leads to less
      lymphorrhea. Furthermore, dissection of station 7 nodes is performed after each
      main bronchus or right intermediate bronchus is taped with a 0 silk suture, which
      is then brought out of the thorax through the access incision for antero-lateral
      retraction of the tracheal carina. We dissect between 3 and 4 N2 lymph node
      stations and a total of approximately 20 N2 lymph nodes. Postoperative
      complications related to MLND occurred in 35 of 992 patients (3.5%), 15 (1.5%)
      for recurrent laryngeal nerve injury, 3 (0.3%) for bilateral vagal injury, 14
      (1.4%) for chylothorax and 3 (0.3%) for airway injury. However, none were lethal.
      Thoracoscopic mediastinal dissection is safe and feasible in treating lung
      cancer. We believe our technique and VSS are very useful for thoracoscopic MLND.

PMID- 22643667
TI  - Thoracoscopic mediastinal lymph node dissection for lung cancer.

PMID- 22643668
TI  - Handsewn proximal anastomoses onto the ascending aorta through a small left
      thoracotomy during minimally invasive multivessel coronary artery bypass
      grafting: a stepwise approach to safety and reproducibility.
AB  - Minimally invasive coronary artery bypass grafting (MICS CABG) is a nonrobotic,
      nonthoracoscopic operation that achieves complete anatomical graft similarity
      with conventional CABG, while avoiding sternotomy and cardiac anoxia. We describe
      the stepwise approach to perform proximal anastomoses directly off the ascending
      aorta and also early results of this operation. All myocardial territories are
      accessed via a 4- to 6-cm left fifth intercostal thoracotomy. After takedown of
      the left internal thoracic artery, the ascending aorta is progressively brought
      into view by the following maneuvers: (1) administration of cardiac inotropes to
      minimize right ventricle filling, (2) increase in right lung positive end
      expiratory pressures and tidal volumes, (3) placement of multilevel pericardial
      retractions, (4) leftward displacement of the ascending aorta with a gauze
      anterior to the superior vena cava, and (5) left posteroinferior displacement of
      the right ventricular outflow tract with an epicardial stabilizer. Handsewn
      proximal anastomoses can then be performed on the ascending aorta with a side
      biting clamp. In the first 100 patients who underwent multivessel MICS CABG with
      proximal anastomoses directly off the aorta, the mean age was 62.6 +/- 10.2
      years, and median operative time was 3.5 hours. The mean number of grafts was 2.3
      +/- 0.5, and there were 3 conversions to open sternotomy. There were no
      preoperative deaths, 2 reoperations for bleeding, and 2 superficial wound
      infections. The median length of hospital stay was 4 days. MICS CABG is a safe
      alternative to conventional CABG, with excellent short-term results.

PMID- 22643670
TI  - On the Diels-Alder dimerisation of cross-conjugated trienes.
AB  - The first general synthesis of 1-substituted [3]dendralenes has led to the
      discovery that conjugating groups significantly enhance the rate of Diels-Alder
      dimerisation relative to both the parent [3]dendralene and to other substituted
      systems.

PMID- 22643669
TI  - Murine superficial lymph node surgery.
AB  - In the field of immunology, to understand the progression of an immune response
      against a vaccine, an infection or a tumour, the response is often followed over
      time. Similarly, the study of lymphocyte homeostasis requires time course
      experiments. Performing these studies within the same mouse is ideal to reduce
      the experimental variability as well as the number of mice used. Blood withdrawal
      allows performance of time course experiments, but it only gives information
      about circulating lymphocytes and provides a limited number of cells. Since
      lymphocytes circulating through the body and residing in the lymph nodes have
      different properties, it is important to examine both locations. The sequential
      removal of lymph nodes by surgery provides a unique opportunity to follow an
      immune response or immune cell expansion in the same mouse over time.
      Furthermore, this technique yields between 1-2x10(6) cells per lymph node which
      is sufficient to perform phenotypic characterization and/or functional assays.
      Sequential lymph node surgery or lymphadenectomy has been successfully used by us
      and others. Here, we describe how the brachial and inguinal lymph nodes can be
      removed by making a small incision in the skin of an anesthetised mouse. Since
      the surgery is superficial and done rapidly, the mouse recovers very quickly,
      heals well and does not experience excessive pain. Every second day, it is
      possible to harvest one or two lymph nodes allowing for time course experiments.
      This technique is thus suitable to study the characteristics of lymph node
      residing lymphocytes over time. This approach is suitable to various experimental
      designs and we believe that many laboratories would benefit from performing
      sequential lymph node surgeries.

PMID- 22643671
TI  - PharmGKB summary:  very important pharmacogene information for GSTT1.

PMID- 22643681
TI  - The pharmacology of McN-A-343.
AB  - The unusual pharmacology of McN-A-343 was first described by Roszowski in 1961.
      The agonist appeared to be a selective stimulant of muscarinic receptors in
      sympathetic ganglia, now known to be the muscarinic M1 receptor subtype. However,
      subsequent research demonstrated that McN-A-343 is a partial agonist with similar
      affinity at all five muscarinic acetylcholine receptor subtypes and its relative
      selectivity depends on a higher efficacy at the M1 (and M4) subtypes. Being a
      partial agonist its action is also dependent on factors, such as receptor density
      and coupling efficacy between receptor activation and tissue response.
      Nevertheless, the relatively high efficacy at M1 receptors led to its widespread
      use as an aid to distinguish responses mediated through M1 receptors from those
      utilizing M2 or M3 muscarinic receptor subtypes, especially in the CNS. There is
      also evidence that it has an allosteric action at some receptor subtypes.
      Recently, it was demonstrated that McN-A-343 can bind to an allosteric site on
      the M2 receptor as well as to the orthosteric site and has thus been termed a
      "bitopic agonist". This allosteric site differs from that occupied by allosteric
      modulators, such as gallamine. Comparison of comparable mutagenic changes in M2
      and M4 receptors also suggests that McN-A-343 utilizes different regions of the
      two receptors for ERK1/2 activation. McN-A-343 has a number of non-muscarinic
      actions. These include activation of some types of nicotinic acetylcholine
      receptors, antagonism of serotonin 5-HT3 and 5-HT4 receptor subtypes, inhibition
      of the uptake mechanism and a local anesthetic action.

PMID- 22643694
TI  - Methods for study of neuronal morphogenesis: ex vivo RNAi electroporation in
      embryonic murine cerebral cortex.
AB  - The cerebral cortex directs higher cognitive functions. This six layered
      structure is generated in an inside-first, outside-last manner, in which the
      first born neurons remain closer to the ventricle while the last born neurons
      migrate past the first born neurons towards the surface of the brain. In addition
      to neuronal migration, a key process for normal cortical function is the
      regulation of neuronal morphogenesis. While neuronal morphogenesis can be studied
      in vitro in primary cultures, there is much to be learned from how these
      processes are regulated in tissue environments. We describe techniques to analyze
      neuronal migration and/or morphogenesis in organotypic slices of the cerebral
      cortex. A pSilencer modified vector is used which contains both a U6 promoter
      that drives the double stranded hairpin RNA and a separate expression cassette
      that encodes GFP protein driven by a CMV promoter. Our approach allows for the
      rapid assessment of defects in neurite outgrowth upon specific knockdown of
      candidate genes and has been successfully used in a screen for regulators of
      neurite outgrowth. Because only a subset of cells will express the RNAi
      constructs, the organotypic slices allow for a mosaic analysis of the potential
      phenotypes. Moreover, because this analysis is done in a near approximation of
      the in vivo environment, it provides a low cost and rapid alternative to the
      generation of transgenic or knockout animals for genes of unknown cortical
      function. Finally, in comparison with in vivo electroporation technology, the
      success of ex vivo electroporation experiments is not dependant upon proficient
      surgery skill development and can be performed with a shorter training time and
      skill.

PMID- 22643695
TI  - Cycloruthenated sensitizers: improving the dye-sensitized solar cell with
      classical inorganic chemistry principles.
AB  - A divergence from the conventional approach to chromophore design has led to the
      establishment of many exciting new benchmarks for the dye-sensitized solar cell
      (DSSC), including the first documented power conversion efficiency in excess of
      12% at 1 sun illumination [Yella et al., Science 2011, 334, 629]. Paramount to
      these advances is the deviation from polypyridyl ruthenium dyes bearing NCS(-)
      ligands, such as [Ru(dcbpy)(2)(NCS)(2)] (N3; dcbpy = 4,4'-dicarboxy-2,2'
      bipyridine). While metal-free and porphyrin dyes have demonstrated much promise,
      the discovery that the NCS(-) ligands of N3 can be replaced by anionic, chelating
      cyclometalating ligands without compromising device efficiencies has ushered in a
      new era of ruthenium dye development. A particularly appealing feature of this
      class of dyestuff is that they offer acute control of the frontier molecular
      orbitals to enable the precise attenuation of both the ground and excited state
      redox potentials through judicious chemical modification of the aryl ring. This
      Perspective summarizes very recent developments in the field, and demonstrates
      how the new and rapidly expanding class of Ru-based sensitizers provides a
      conduit for enhancing the performance (and potentially the stability) of the
      DSSC.

PMID- 22643703
TI  - Renal and urologic problems:  management of ureteric obstruction.
AB  - PURPOSE OF REVIEW: The purpose of this article is to review the recent literature
      concerning obstructive uropathy from advanced cancer. This factor is relevant as
      it is often a difficult task for physicians to estimate a patient's life
      expectancy and evaluate the possible benefit of urinary diversion. Recent
      research has addressed this issue. We now have objective criteria to stratify the
      possible benefit of urinary diversion in patients with malignant obstructive
      nephropathy. RECENT FINDINGS: When dealing with ureteric obstruction treatment
      must be individualized and risk stratification is of paramount importance. There
      is no clear evidence that urinary diversion improves quality of life and
      treatment decisions must be individualized. The decision to treat obstructive
      nephropathy in the palliative setting should include the patient, his family and
      members of the support team. SUMMARY: Ureteric stents and percutaneous
      nephrostomies are the preferred initial treatment options, although stent
      infection, encrustation and blockages are common problems. New compression
      resistant metallic stents seem promising for patients with a malignant disease
      who require long-term urinary drainage. When more conservative measures have
      failed, supra-vesical reconstruction and diversion may be an option.

PMID- 22643704
TI  - Metastatic bladder cancer:  anything new?
AB  - PURPOSE OF REVIEW: Although bladder cancer is considered a chemosensitive
      disease, the prognosis of patients with metastatic disease is still poor with
      median survival being approximately 12-14 months in good prognosis patients and
      with cure in only a minority of patients. The addition of new drugs to the
      standard cisplatin-based regimens has not improved these figures. The purpose of
      this review is to highlight the role of chemotherapy and the impact of the new
      targeted agents in the treatment of metastatic bladder carcinoma. RECENT
      FINDINGS: A better understanding of the biology of the molecular patterns of
      urothelial bladder cancer has led to the clinical investigation of several
      therapeutic targets such as antiangiogenics, anti-EGFR agents, and
      immunomodulatory agents. To date, these agents have yet to demonstrate an
      improvement in overall survival. The molecular alterations that drive platinum
      resistance and the study of the genetic profiles will help to identify the
      prognostic and predictive biomarkers. SUMMARY: No major advances have been
      achieved in the recent years in the treatment of urothelial carcinoma of the
      bladder. Chemotherapy remains the mainstay of treatment of metastatic disease.
      Several targeted agents are currently under investigation, but no major
      breakthroughs have been achieved with these drugs. Development of less toxic,
      more effective agents is crucial and clinical trial participation needs to be
      emphasized.

PMID- 22643705
TI  - Atypical femoral fractures:  epidemiology, etiology, and patient management.
AB  - PURPOSE OF REVIEW: To review the definition, epidemiology, and putative
      pathophysiology of atypical femoral fractures and propose strategies for the
      management of patients with atypical fractures as well as patients on long-term
      bisphosphonates without atypical fractures. RECENT FINDINGS: Recent epidemiologic
      evidence shows that the absolute incidence of atypical femoral fractures is small
      compared with the incidence of typical hip fractures. However, long-term
      bisphosphonate use may be an important risk factor for atypical fractures, and
      minimal additional antifracture benefit has been demonstrated for treatment
      durations longer than 5 years for patients with postmenopausal osteoporosis. This
      review gives advice to aid clinicians in the management of patients with
      incipient or complete atypical fractures. SUMMARY: Extremely limited evidence is
      available for how best to manage patients with atypical fractures. A
      comprehensive metabolic approach for the management of patients on long-term
      bisphosphonates will help to prevent oversuppression of bone remodeling that is
      implicated in the pathogenesis of these fractures.

PMID- 22643706
TI  - T-cell receptor diversity prevents T-cell lymphoma development.
AB  - Mature T-cell lymphomas (MTCLs) have an extremely poor prognosis and are much
      less frequent than immature T-cell leukemias. This suggests that malignant
      outgrowth of mature T lymphocytes is well controlled. Indeed, in a previous study
      we found that mature T cells are resistant to transformation with known T-cell
      oncogenes. Here, however, we observed that T-cell receptor (TCR) mono
      /oligoclonal mature T cells from TCR transgenic (tg) mice (OT-I, P14) expressing
      the oncogenes NPM/ALK or DeltaTrkA readily developed MTCLs in T-cell-deficient
      recipients. Analysis of cell surface markers largely ruled out that TCR tg
      lymphomas were derived from T-cell precursors. Furthermore, cotransplanted non
      modified TCR polyclonal T cells suppressed malignant outgrowth of oncogene
      expressing TCR tg T lymphocytes. A dominant role of an anti-leukemic immune
      response or Tregs in the control of MTCLs seems unlikely as naive T cells derived
      from oncogene expressing stem cells, which should be tolerant to leukemic
      antigens, as well as purified CD4 and CD8 were resistant to transformation.
      However, our results are in line with a model in which homeostatic mechanisms
      that stabilize the diversity of the normal T-cell repertoire, for example, clonal
      competition, also control the outgrowth of potentially malignant T-cell clones.
      This study introduces a new innate mechanism of lymphoma control.

PMID- 22643707
TI  - Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of
      benzene-exposed workers.
AB  - Benzene exposure causes acute myeloid leukemia and hematotoxicity, shown as
      suppression of mature blood and myeloid progenitor cell numbers. As the leukemia
      related aneuploidies monosomy 7 and trisomy 8 previously had been detected in the
      mature peripheral blood cells of exposed workers, we hypothesized that benzene
      could cause leukemia through the induction of these aneuploidies in hematopoietic
      stem and progenitor cells. We measured loss and gain of chromosomes 7 and 8 by
      fluorescence in situ hybridization in interphase colony-forming unit-granulocyte
      macrophage (CFU-GM) cells cultured from otherwise healthy benzene-exposed (n=28)
      and unexposed (n=14) workers. CFU-GM monosomy 7 and 8 levels (but not trisomy)
      were significantly increased in subjects exposed to benzene overall, compared
      with levels in the control subjects (P=0.0055 and P=0.0034, respectively). Levels
      of monosomy 7 and 8 were significantly increased in subjects exposed to <10
      p.p.m. (20%, P=0.0419 and 28%, P=0.0056, respectively) and >= 10 p.p.m. (48%,
      P=0.0045 and 32%, 0.0354) benzene, compared with controls, and significant
      exposure-response trends were detected (P(trend)=0.0033 and 0.0057). These data
      show that monosomies 7 and 8 are produced in a dose-dependent manner in the blood
      progenitor cells of workers exposed to benzene, and may be mechanistically
      relevant biomarkers of early effect for benzene and other leukemogens.

PMID- 22643708
TI  - Use of iron-fortified rice reduces anemia in infants.
AB  - Food fortification is advocated to tackle iron deficiency in anemic populations.
      Our objective was to evaluate the impact of iron-fortified rice (Ultrarice((r)))
      weekly on hemoglobin and anemia levels compared with standard rice (control).
      This cluster-randomized study deals with infants (10-23 months) from two public
      child day care centers in Brazil, n = 216, in an 18 week intervention. The
      intervention group received individual portions of fortified rice (50 g) provided
      56.4 mg elemental/Fe. For intervention center: baseline mean hemoglobin was 11.44
      +/- 1.07 g/dl, and after intervention 11.67 +/- 0.96 g/dl, p < 0.029; for
      control: baseline mean hemoglobin value was 11.35 +/- 4.01 g/dl, and after
      intervention 11.36 +/- 2.10 g/dl, p = 0.986. Anemia prevalence for intervention
      center was 31.25% at baseline, and 18.75% at end of study, p = 0.045; for control
      43.50% were anemic at baseline, and 37.1% at the end of study, p = 0.22. Number
      Needed to Treat was 7. Iron-fortified rice was effective in increasing hemoglobin
      levels and reducing anemia in infants.

PMID- 22643713
TI  - Stem cell-based therapies: promises, obstacles, discordance, and the agora.
AB  - Stem cell research has entered the public consciousness through the media.
      Proponents and opponents of all such research, or of human embryonic stem cell
      research specifically, engage in heated exchanges in the modern public forum
      where stakeholders negotiate, the agora. One common claim that emerges from the
      fray is that a particular type of stem cell research should be pursued as the
      most promising path toward the reduction of suffering and untimely death for all
      of humanity. Upon evaluation, experimental data regarding the potential role of
      stem cells in regenerative therapies for three conditions-spinal cord injury,
      type 1 diabetes, and cardiovascular disease-tell distinct, complex, and
      inconclusive stories. Further analyses in this article incorporate realistic
      considerations of a broad range of relevant factors: limited funding for
      biomedical research, media motives, the discordance hypothesis of evolutionary
      medicine, the relationship between religion and science, medical care in
      developing nations, and culture wars over abortion. Holistic investigation
      inspired by the current agora conversation supports the need to drastically
      change interactions regarding stem cell research so that its potential to benefit
      humanity may be more fully realized.

PMID- 22643714
TI  - Menstruation, perimenopause, and chaos theory.
AB  - This article argues that menstruation, including the transition to menopause,
      results from a specific kind of complex system, namely, one that is nonlinear,
      dynamical, and chaotic. A complexity-based perspective changes how we think about
      and research menstruation-related health problems and positive health. Chaotic
      systems are deterministic but not predictable, characterized by sensitivity to
      initial conditions and strange attractors. Chaos theory provides a coherent
      framework that qualitatively accounts for puzzling results from perimenopause
      research. It directs attention to variability within and between women,
      adaptation, lifespan development, and the need for complex explanations of
      disease. Whether the menstrual cycle is chaotic can be empirically tested, and a
      summary of our research on 20- to 40-year-old women is provided.

PMID- 22643715
TI  - The placebo effect: how the subconscious fits in.
AB  - The placebo effect is very well known, being replicated in many scientific
      studies. At the same time, its exact mechanisms still remain unknown. Quite a few
      hypothetical explanations for the placebo effect have been suggested, including
      faith, belief, hope, classical conditioning, conscious/subconscious expectation,
      endorphins, and the meaning response. This article argues that all these
      explanations may boil down to autosuggestion, in the sense of "communication with
      the subconscious." An important implication of this is that the placebo effect
      can in principle be used effectively without the placebo itself, through a direct
      use of autosuggestion. The benefits of such a strategy are clear: fewer side
      effects from medications, huge cost savings, no deception of patients, relief of
      burden on the physician's time, and healing in domains where medication or other
      therapies are problematic.

PMID- 22643717
TI  - Ethics of the heart: ethical and policy challenges in the treatment of advanced
      heart failure.
AB  - Heart failure is a major cause of morbidity and mortality in the United States
      and worldwide, accounting for immense health-care costs. Advanced therapies such
      as transplantation, ventricular assist devices, and implantable cardioverter
      defibrillators have had great success in significantly improving life expectancy
      and morbidity, however these advances have contributed substantially to the
      economic burden associated with this epidemic. Concomitantly, the accessibility
      of these advanced therapies is limited, due to a finite number of available
      organs for heart transplantation and, in the future, the economic costs
      associated with both transplant and device therapy. This article discusses
      ethical and policy challenges in the treatment of advanced heart failure,
      including decisions regarding procurement of hearts for transplant and allocation
      to recipients; and the complex issues surrounding the use of implantable
      cardioverter defibrillators and ventricular assist devices, including quality of
      life, advanced directive planning in the context of these devices, and resource
      utilization. Based on these challenges, we recommend that a discussion of these
      complex matters be incorporated into cardiovascular training programs.

PMID- 22643716
TI  - Interpreting evidence: why values can matter as much as science.
AB  - Despite increasing awareness of the ways in which non-epistemic values play roles
      in science, many scientists remain reluctant to acknowledge values at stake in
      their own work. Even when research clearly relates to risk assessment and
      establishing public policy, contexts in which the presence of values is less
      likely to be contentious, scientists tend to present such research as merely
      involving empirical questions about what the evidence is. As a result, debates
      over policy-related science tend to be framed as purely epistemic debates over
      the state of the evidence. We argue that this neglects the important ways that
      ethical and social values play legitimate roles in judgments about what we take
      to be evidence for a particular policy. Using the case of recent disputes about
      the relative safety of home birth, we argue that although the debate has been
      framed as a purely scientific one about the empirical evidence for home birth, it
      actually involves disagreements about underlying value assumptions. If our claims
      are correct, then in order to move the debate forward, scientists will need to
      engage in a critical discussion about the values at stake.

PMID- 22643718
TI  - Philosophy's loss, neurology's gain: the endeavor of John Hughlings-Jackson.
AB  - The year 2011 marked the centenary of the death of one of the founders of British
      neurology, John Hughlings-Jackson (1835-1911). By common consent he was a great
      clinician. But he was more. He endeavored to use clinical observations to throw
      light on one of the great problems of the modern world, the problem of mind.
      Hughlings-Jackson's daily contact with mentalities warped by neurological disease
      caused him to ponder deeply the nature of the mind-brain relationship, nowadays
      often known simply as the "hard problem." In particular, he saw the danger of
      conflating mind and brain, a danger that has grown greater with the spectacular
      growth of neuroscientific knowledge during the last century. Although Hughlings
      Jackson's neuroscientific thought is long outdated, his philosophic endeavors
      remain highly instructive.

PMID- 22643719
TI  - Vaccination-induced syphilis and the Hubner malpractice litigation.
AB  - This article examines smallpox vaccination in the 19th century as background for
      a notorious medical malpractice case that occupied Bavarian courts from April
      1853 until May 1854. Dr. Georg Hubner, the defendant, was accused of having
      initiated a small epidemic of syphilis by using the lymph of a syphilitic infant
      to vaccinate 13 infants. The litigation and its published contemporaneous
      discussion demonstrate conflicts in the understanding of syphilis, the hazards of
      having to make a purely clinical diagnosis, the effect of obsolete legal wording
      in medical litigation, and the attitude of leading physicians to a guilty
      colleague. This case ultimately led to efforts to make arm-to-arm smallpox
      vaccination safer, and by 1898 to abandon the technique in favor of bovine
      sources that were sterilized and stabilized by various methods.

PMID- 22643720
TI  - The foundation of physicianship.
AB  - Although the practice of medicine continually changes in response to new
      biomedical understanding, novel technologies, and evolving cultural contexts, the
      ethical foundations of the clinical relationship between patient and physician
      paradoxically remain constant. There are fundamental characteristics with respect
      to character, behavior, and responsibilities that are descriptive of and
      necessary to the role of healer and that underpin the notion of physicianship.
      This article discusses the underlying characteristics or virtues that are
      necessary to the practice of medicine from the perspectives of three different
      philosophic traditions: the Aristotelian idea of phronesis as developed in the
      work of Edmund Pellegrino; the notion of alterity as framed by Emmanuel Levinas;
      and the attributes necessary to healing as laid out in the kabbala.

PMID- 22643721
TI  - Teaching within the operating theater.
AB  - All surgeons within teaching hospitals share in the collective responsibility for
      training more junior doctors. A large proportion of training focuses around
      developing good clinical practice and ensuring the trainee is reaching
      competency. Formal structured teaching sessions aim to improve the trainee's
      theoretical knowledge and wider understanding. But surgical trainees must also
      learn how to operate. In order to do this, a more experienced surgeon must teach
      and supervise them in how to perform common procedures. This article discusses
      effective teaching within the operating theater, drawing on the author's own
      reflective practice. It introduces the concepts of theater prerequisites, used
      for assessing the suitability of theater cases for teaching, and active
      observation as one of the methodologies for teaching in theater.

PMID- 22643722
TI  - Group-based and personalized care in an age of genomic and evidence-based
      medicine: a reappraisal.
AB  - This article addresses the philosophical and moral foundations of group-based and
      individualized therapy in connection with population care equality. The U.S. Food
      and Drug Administration (FDA) recently modified its public health policy by
      seeking to enhance the efficacy and equality of care through the approval of
      group-specific prescriptions and doses for some drugs. In the age of genomics,
      when individualization of care increasingly has become a major concern,
      investigating the relationship between population health, stratified medicine,
      and personalized therapy can improve our understanding of the ethical and
      biomedical implications of genomic medicine. I suggest that the need to optimize
      population health through population substructure-sensitive research and the need
      to individualize care through genetically targeted therapies are not necessarily
      incompatible. Accordingly, the article reconceptualizes a unified goal for modern
      scientific medicine in terms of individualized equal care.

PMID- 22643723
TI  - In search of lost opportunities: Marcel Proyce and James Joust discuss doctors,
      diseases, life and death (a hypothetical conversation between Marcel Proust and
      James Joyce).
AB  - Two of the most influential thinkers of the last century, Marcel Proust (1871
      1922) and James Joyce (1882-1941), met in 1922 but had little to say to each
      other. Had circumstances been different, what might they have said? They had much
      in common, including an interest in doctors and diseases, but from different
      perspectives. Although the meeting was a lost opportunity to explore the insights
      of two great analysts of the human condition, their lives and works provide a
      record rich in detail and timeless in relevance. From this, we construct what
      might have been overheard during a conversation between Marcel Proyce and James
      Joust almost a century ago.

PMID- 22643724
TI  - The effect of supported standing in adults with upper motor neurone disorders: a
      systematic review.
AB  - OBJECTIVES: To evaluate whether supported standing can affect lower limb muscle
      length, spasticity, bone mineral density or the function of adults with upper
      motor neurone disorders. DATA SOURCES: A search was conducted of MEDLINE, EMBASE,
      AMED, CINAHL and Cochrane library electronic databases; clinical trial registers
      via www.controlled-trials.com and complemented with citation tracking. REVIEW
      METHODS: Two reviewers independently evaluated eligibility and methodological
      quality. Class I and II studies of assisted standing for adults with stroke,
      multiple sclerosis, traumatic brain injury or spinal cord injury were eligible. A
      domain-based risk of bias approach was used to assess quality. RESULTS: Seventeen
      studies were included: 11 class I and 6 class II studies involving 540
      participants, of whom 73% were non-ambulant. Quality was generally low, with only
      two high quality trials identified. High-quality evidence suggested tilt-table
      standing has a small effect on preventing loss of ankle dorsiflexion. One high
      quality study found a low-dose standing programme did not alter bone loss early
      after spinal injury. Class II low-quality evidence suggested long-term, higher
      dose programmes may slow bone loss. Limited evidence for the effectiveness of
      standing on spasticity and function was inconclusive. CONCLUSION: Supported
      standing can prevent small losses of ankle mobility but the clinical importance
      of these effects is uncertain. Low-dose standing is unlikely to protect bone
      health.

PMID- 22643725
TI  - Interferential light therapy in the treatment of shoulder tendinopathies: a
      randomized controlled pilot study.
AB  - OBJECTIVES: To test the safety of the diode light therapy and evaluate the
      advantages of the interferential effect of two light probes versus a conventional
      light probe in the relief of shoulder pain and disability caused by shoulder
      tendinopathies. DESIGN: Randomized single-blind pilot study. SETTING: Clinical
      electrotherapy unit. PARTICIPANTS: A total of 30 patients with shoulder pain from
      tendinopathies. INTERVENTIONS: The patients were randomly assigned into two
      groups. Group 1 (n = 15) received interferential light therapy generated by two
      independent and identical cluster probes composed of light emitting and
      superluminescent diodes. Similarly, two applicators were applied in group 2 (n =
      15), but only one was active, as in conventional clinical therapy. Each multi
      diode cluster probe was composed of seven light-emitting diodes at 600 nm and 12
      superluminescent diodes at 950 nm. MAIN OUTCOME MEASURES: Pain was evaluated by
      visual analogue scale (VAS) at day, at night and during several shoulder
      movements. Shoulder functional status was measured by means of the University
      California Los Angeles scale (UCLA). RESULTS: Comparison between both treatments
      using the Mann-Whitney U-test showed better results for the interferential
      treatment. There were significant differences in pain reduction during abduction
      (P < 0.05) and external rotation (P < 0.05), with pain reductions in abduction
      and external rotation of 1.5 (+/- 1.3) and 0.5 (+/- 1.0) respectively.
      CONCLUSION: Interferential light therapy was safe and effective regarding the
      shoulder pain reduction during abduction and external rotation movements. The
      estimated size sample needed for future two-treatment parallel-design studies
      will require about 60 patients.

PMID- 22643726
TI  - Oral nutritional support of older (65 years+) medical and surgical patients after
      discharge from hospital: systematic review and meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVE: To estimate the effectiveness of oral nutritional support compared to
      placebo or usual care in improving clinical outcome in older (65 years+) medical
      and surgical patients after discharge from hospital. Outcome goals were: re
      admissions, survival, nutritional and functional status, quality of life and
      morbidity. DATA SOURCES: Three recent Cochrane reviews and an update of their
      literature search using MEDLINE, EMBASE, Web of Science. Search terms included
      randomized controlled trials; humans; age 65+ years; subset: dietary supplements.
      REVIEW METHODS: One reviewer assessed trials for inclusion, extracted data and
      assessed trial quality. RESULTS: Six trials were included (N = 716 randomly
      assigned participants). All trials used oral nutritional supplements. A positive
      effect on nutritional intake (energy) and/or nutritional status (weight) (in
      compliant participants) were observed in all trials. Two pooled analysis was
      based on a fixed-effects model. No significant effect were found on mortality
      (four randomized controlled trials with 532 participants, odds ratio 0.80 (95%
      confidence (CI) interval 0.46 to 1.39)) or re-admissions (four randomized
      controlled trials with 478 participants, odds ratio 1.07 (95% CI 0.71 to 1.61)).
      CONCLUSION: Although the evidence is limited, we suggest that oral nutritional
      support may be considered for older malnourished medical and surgical patients
      after discharge from hospital.

PMID- 22643727
TI  - The effects of toe spreader in people with overactive toe flexors post stroke: a
      randomized controlled pilot study.
AB  - OBJECTIVES: To investigate the long-term effects of the toe spreader on gait
      characteristics, pain, activity level and balance in individuals with chronic
      stroke who exhibited tonic toe flexion reflex. The secondary objectives were to
      determine the sample size for future studies and to assess compliance to the use
      of the toe spreader. DESIGN: Single-blind, randomized controlled pilot trial.
      SETTING: Outpatient clinic of a tertiary hospital in Singapore. SUBJECTS: Nine
      ambulatory participants with tonic toe flexion reflex more than six months post
      stroke. INTERVENTION: Control or customized toe spreader groups for six months.
      The toe spreader was made of Rolyan Ezemix elastomer putty and worn with sport
      sandals during ambulation. MAIN MEASURES: Gait speed and plantar surface contact
      area, pain visual analogue scale (VAS), Berg Balance Scale, Modified Ashworth
      Scale, activity level measured on pedometer and compliance via logbook. RESULTS:
      There were no significant differences between the groups. Both groups showed non
      significant improvements in gait speed (toe spreader 0.34 (0.26) versus 0.37
      (0.29) m/s; control 0.40 (0.27) versus 0.50 (0.17) m/s), activity level, step
      length of the hemiplegic leg and stride length at six months. All participants in
      the intervention group used the toe spreader less than 50% of the days,
      indicating suboptimal compliance. CONCLUSION: The use of the toe spreader did not
      result in significant improvements in any outcomes. Studies with sample sizes of
      at least 56 participants and strategies to increase compliance to the use of the
      toe spreader are recommended.

PMID- 22643728
TI  - Isolation and culture of human fungiform taste papillae cells.
AB  - Taste cells are highly specialized, with unique histological, molecular and
      physiological characteristics that permit detection of a wide range of simple
      stimuli and complex chemical molecules contained in foods. In human, individual
      fungiform papillae contain from zero to as many as 20 taste buds. There is no
      established protocol for culturing human taste cells, although the ability to
      maintain taste papillae cells in culture for multiple cell cycles would be of
      considerable utility for characterizing the molecular, regenerative, and
      functional properties of these unique sensory cells. Earlier studies of taste
      cells have been done using freshly isolated cells in primary culture, explant
      cultures from rodents, or semi-intact taste buds in tissue slices. Although each
      of these preparations has advantages, the development of long-term cultures would
      have provided significant benefits, particularly for studies of taste cell
      proliferation and differentiation. Several groups, including ours, have been
      interested in the development and establishment of taste cell culture models.
      Most attempts to culture taste cells have reported limited viability, with cells
      typically not lasting beyond 3-5 d. We recently reported on a successful method
      for the extended culture of rodent taste cells. We here report for the first time
      the establishment of an in vitro culture system for isolated human fungiform
      taste papillae cells. Cells from human fungiform papillae obtained by biopsy were
      successfully maintained in culture for more than eight passages (12 months)
      without loss of viability. Cells displayed many molecular and physiological
      features characteristic of mature taste cells. Gustducin and phospholipase C
      beta2, (PLC-beta2) mRNA were detected in many cells by reverse transcriptase
      polymerase chain reaction and confirmed by sequencing. Immunocytochemistry
      analysis demonstrated the presence of gustducin and PLC-beta2 expression in
      cultured taste cells. Cultured human fungiform cells also exhibited increases in
      intracellular calcium in response to appropriate concentrations of several taste
      stimuli indicating that taste receptors and at least some of the signalling
      pathways were present. These results sufficient indicate that taste cells from
      adult humans can be generated and maintained for at least eight passages. Many of
      the cells retain physiological and biochemical characteristics of acutely
      isolated cells from the adult taste epithelium to support their use as a model
      taste system. This system will enable further studies of the processes involved
      in proliferation, differentiation and function of mammalian taste receptor cells
      in an in vitro preparation. Human fungiform taste papillae used for establishing
      human fungiform cell culture were donated for research following proper informed
      consent under research protocols that were reviewed and approved by the IRB
      committee. The protocol (#0934) was approved by Schulman Associates Institutional
      Review Board Inc., Cincinnati, OH. Written protocol below is based on published
      parameters reported by Ozdener et al. 2011.

PMID- 22643729
TI  - Prevention of human enterovirus 71 infection by kappa carrageenan.
AB  - Enterovirus 71 (EV 71), the newest member of Enteroviridae, is notorious for its
      etiological role in epidemics of the hand-foot-and-mouth disease, particularly in
      association with fatal neurological complications in young children. Searching
      for new and more effective agents against EV 71 infections has never relented as
      corresponding vaccines or antiviral drugs remain unavailable. Sulfated
      polysaccharides from seaweed are known to possess a broad range of biological
      activities across anti-virus, anti-tumor, immunomodulation, anti-coagulation,
      etc. In this study, we report kappa carrageenan also has a strong and effective
      anti-EV 71 activity able to reduce plaque formation, prevent viral replication
      before or during viral adsorption, as well as inhibit EV 71-induced apoptosis. In
      virus binding assay, kappa carrageenan was shown able to bind EV 71 firmly,
      forming carrageenan-viruses complexes, whereby the virus-receptor interaction is
      likely disrupted. Added together, kappa carrageenan may be an ideal candidate
      worthwhile to develop into anti-EV 71 agents.

PMID- 22643730
TI  - Recent progress in henipavirus research: molecular biology, genetic diversity,
      animal models.
AB  - Nipah and Hendra virus are members of a newly identified genus of emerging
      paramyxoviruses, the henipaviruses. Both viruses have the ability to cause severe
      pulmonary infection and severe acute encephalitis. Following their discovery in
      the 1990s, outbreaks caused by these zoonotic paramyxoviruses have been
      associated with high public health and especially economic threat potential.
      Currently, only geographic groupings in Asia and Australia have been described
      for the henipaviruses. However, while few viral isolates are available and more
      detailed characterization is necessary, there has been recent evidence that
      divergent henipaviruses might be present on the African continent. This review
      endeavours to capture recent advances in the field of henipavirus research, with
      a focus on genome structure and replication mechanisms, reservoir hosts, genetic
      diversity, pathogenesis and animal models.

PMID- 22643736
TI  - Synthesis of sterically hindered enamides via a Ti-mediated condensation of
      amides with aldehydes and ketones.
AB  - The first TiCl(4)-mediated condensation of secondary amides with aldehydes and
      ketones has been achieved. The reaction proceeds at room temperature and is
      complete within 5 h in most cases. The optimized procedure used 5 equiv of an
      amine base hinting that the in situ activation of both the amide and the Lewis
      acid is required. The reaction affords polysubstituted (E)-enamides.

PMID- 22643737
TI  - Microfluidic droplet sorting with a high frequency ultrasound beam.
AB  - This paper presents experimental results demonstrating the feasibility of high
      frequency ultrasonic sensing and sorting for screening single oleic acid (lipid
      or oil) droplets under continuous flow in a microfluidic channel. In these
      experiments, hydrodynamically focused lipid droplets of two different diameters
      (50 MUm and 100 MUm) are centered along the middle of the channel, which is
      filled with deionized (DI) water. A 30 MHz lithium niobate (LiNbO(3)) transducer,
      placed outside the channel, first transmits short sensing pulses to non
      invasively determine the acoustic scattering properties of the individual
      droplets passing through the beam's focus. Integrated backscatter (IB)
      coefficients, utilized as a sorting criterion, are measured by analyzing the
      received echo signals from each droplet. When the IB values corresponding to 100
      MUm droplets are obtained, a custom-built LabVIEW panel commands the transducer
      to emit sinusoidal burst signals to commence the sorting operation. The number of
      droplets tested for the sorting is 139 for 50 MUm droplets and 95 for 100 MUm
      droplets. The sensing efficiencies are estimated to be 98.6% and 99.0%,
      respectively. The sorting is carried out by applying acoustic radiation forces to
      100 MUm droplets to direct them towards the upper sheath flow, thus separating
      them from the centered droplet flow. The sorting efficiencies are 99.3% for 50
      MUm droplets and 85.3% for 100 MUm droplets. The results suggest that this
      proposed technique has the potential to be further developed into a cost
      effective and efficient cell/microparticle sorting instrument.

PMID- 22643738
TI  - GC-based detection of aldononitrile acetate derivatized glucosamine and muramic
      acid for microbial residue determination in soil.
AB  - Quantitative approaches to characterizing microorganisms are crucial for a
      broader understanding of the microbial status and function within ecosystems.
      Current strategies for microbial analysis include both traditional laboratory
      culture-dependent techniques and those based on direct extraction and
      determination of certain biomarkers. Few among the diversity of microbial species
      inhabiting soil can be cultured, so culture-dependent methods introduce
      significant biases, a limitation absent in biomarker analysis. The glucosamine,
      mannosamine, galactosamine and muramic acid have been well served as measures of
      both the living and dead microbial mass, of these the glucosamine (most abundant)
      and muramic acid (uniquely from bacterial cell) are most important constituents
      in the soil systems. However, the lack of knowledge on the analysis restricts the
      wide popularization among scientific peers. Among all existing analytical
      methods, derivatization to aldononitrile acetates followed by GC-based analysis
      has emerged as a good option with respect to optimally balancing precision,
      sensitivity, simplicity, good chromatographic separation, and stability upon
      sample storage. Here, we present a detailed protocol for a reliable and
      relatively simple analysis of glucosamine and muramic acid from soil after their
      conversion to aldononitrile acetates. The protocol mainly comprises four steps:
      acid digestion, sample purification, derivatization and GC determination. The
      step-by-step procedure is modified according to former publications. In addition,
      we present a strategy to structurally validate the molecular ion of the
      derivative and its ion fragments formed upon electron ionization. We applied GC
      EI-MS-SIM, LC-ESI-TOF-MS and isotopically labeled reagents to determine the
      molecular weight of aldononitrile acetate derivatized glucosamine and muramic
      acid; we used the mass shift of isotope-labeled derivatives in the ion spectrum
      to investigate ion fragments of each derivatives. In addition to the theoretical
      elucidation, the validation of molecular ion of the derivative and its ion
      fragments will be useful to researchers using delta(13)C or ion fragments of
      these biomarkers in biogeochemical studies.

PMID- 22643754
TI  - High lactose tolerance in North Europeans: a result of migration, not in situ
      milk consumption.
AB  - The main carbohydrate in milk is lactose, which must be hydrolyzed to glucose and
      galactose before the sugars can be digested. While 65% or more of the total human
      population are lactose intolerant, in some human populations lactase activity
      commonly persists into adulthood. Lactose tolerance is exceptionally widespread
      in Northern European countries such as Sweden and Finland, with tolerance levels
      of 74% and 82%, respectively. Theoretically, this may result either from a strong
      local selection pressure for lactose tolerance, or from immigration of lactose
      tolerant people to Northern Europe. We provide several lines of archaeological
      and historical evidence suggesting that the high lactose tolerance in North
      Europeans cannot be explained by selection from in situ milk consumption. First,
      fresh cow milk has not belonged to the traditional diet of Swedes or Finns until
      recent times. Second, not enough milk has been available for adult consumption.
      Cattle herding has been neither widespread nor productive enough in Northern
      Europe to have provided constant access to fresh milk. We suggest that the high
      prevalence of lactose tolerance in Finland in particular may be explained by
      immigration of people representing so-called Corded Ware Culture, an early
      culture representing agricultural development in Europe.

PMID- 22643755
TI  - Empathy beyond the conceptual level: core nonspecific factors of psychotherapy.
AB  - The human mind contains much more than concepts. By only taking into account the
      conceptual level, a cared-for person may feel utterly lonely and abandoned, not
      deeply in contact with the caregiver, not deeply understood for who he or she
      really is. A chronic pain patient, for instance, may react to a purely conceptual
      level communication, with its lack of deeper contact, by an increasing sense of
      loneliness. This in itself may substantially contribute to the suffering of
      chronic functional pain or even functional disorders in general. In dealing with
      chronic pain patients, as with any patients, it is therefore very important to
      develop a sense of empathy that goes beyond this, towards deeply understanding
      the patient as complete person. This sheds a profound light on the all-important
      nonspecific factors of psychotherapy, which according to many researchers form
      the only profoundly active principle in psychotherapy.

PMID- 22643756
TI  - Mommy, kiss it and make it well: saliva reconsidered-some reflections on
      alloantisepsis.
AB  - Human saliva is a two-edged sword. The mouth can infect, and it can also heal.
      Saliva is a component of the immune system. Many antibacterial factors as well as
      digestive enzymes are present in sputum, and oxidizing agents abet oral defense
      mechanisms. The biological equilibrium of the mouth enhances its antimicrobial
      environment. Saliva cleans the wound by lavage, promoting healing while
      protecting injured tissues. Awareness of both the adverse and salubrious effects
      of sputum should inform the treatment of wounds with oral contact.

PMID- 22643757
TI  - Patients and borders, money and mission: responding to medically needy persons
      from other countries who lack financial resources.
AB  - When financially impoverished persons from resource-poor countries travel to
      resource-rich countries to seek medical treatment, health-care professionals and
      hospital administrators must decide how to respond. These financially
      impoverished "medical travelers" are medically no different from financially
      impoverished citizens or immigrants, but their national residence and purpose of
      travel may cause them to be seen as having a lower degree of standing within the
      communities that hospitals are expected to serve. In responding to such persons,
      health-care professionals and administrators encounter tension between the
      mission-driven intention to provide care and a budget-driven intention to protect
      operating margins. Responses require practical wisdom and a readiness to wrestle
      with tensions related to objectives (charitable versus financial), role-specific
      obligations (clinicians versus administrators), and contrasting moral frameworks.
      There are also challenges of reconciling plural moral values, setting moral
      priorities, and considering whether national borders should constrain our view of
      persons as neighbors. Finding a way forward amidst many tensions is hard moral
      work, but it may be facilitated by granting a moral imperative to physical
      proximity, respecting role-fidelity among clinicians and administrators,
      furthering candid moral dialogue, and promoting a presumption to treat whenever
      it is feasible to do so.

PMID- 22643758
TI  - Pregnancy as a harm?
AB  - Michigan's Appellate Court ruled in 2004 that a pregnancy that resulted from a
      rape should be considered a bodily injury for sentencing purposes. Interestingly,
      all three possible outcomes of a pregnancy-abortion, miscarriage, or childbirth
      are considered to bring with them significant and substantial physical,
      psychological, and emotional changes. While the immediate impact of the ruling in
      People v. Cathey affected only the guilty individual, there are larger
      implications for this ruling beyond just sentencing guidelines. The ruling can be
      considered a step forward in prosecuting rapists, but possibly at the expense of
      reimagining the female body. This article considers the Cathey ruling itself, the
      potential benefits and consequences of this understanding on feminist discourse,
      and, crucially, the impact of this decision on abortion discussions. The central
      question that emerges is, can we both consider pregnancy a harm and believe that
      this harm is not always wrong-making?

PMID- 22643759
TI  - Homage to Henry Beecher (1904-1976).
AB  - The writings of Henry Beecher (1904-1976) have had an enormous influence on
      thinking and practice with respect to the ethics of medicine and clinical
      research. This essay examines the seminal contributions of Beecher as illustrated
      by four landmark articles concerning the ethics of clinical research, the placebo
      effect and placebo-controlled trials, the evaluation of invasive procedures, and
      "brain death" and vital organ transplantation. To appreciate Beecher's legacy, it
      is salutary to explicate the significance of his enduring contributions and to
      critically evaluate their limitations.

PMID- 22643760
TI  - Apollo, sudden death, and Homer's "Odyssey": a warning from the past that we may
      be unable to eradicate coronary artery disease.
AB  - Over recent years there has been a gratifying decrease in the incidence of
      recorded deaths from coronary artery disease in the Western world. The common
      view is that coronary artery disease is a recent phenomenon, that we have been
      subject to an epidemic in the mid-20th century that is now tailing off, and that
      with appropriate risk modification we may eradicate this disease or make it very
      rare. However, this article examines the cases of sudden, nontraumatic death
      described in Homer's Odyssey, which dates from c. 800 BCE. The results suggest
      that a high incidence of death from coronary artery disease may not be a recent
      phenomenon. Together with other described evidence, this study casts doubt on the
      view that coronary artery disease is a modern epidemic that can be eradicated.

PMID- 22643761
TI  - Earl Sutherland (1915-1974) [corrected] and the discovery of cyclic AMP.
AB  - In 1945, Earl Sutherland (1915-1974) [corrected] and associates began studies of
      the mechanism of hormone-induced glycogen breakdown in the liver. In 1956, their
      efforts culminated in the identification of cyclic AMP, an ancient molecule
      generated in many cell types in response to hormonal and other extracellular
      signals. Cyclic AMP, the original "second messenger," transmits such signals
      through pathways that regulate a diversity of cellular functions and
      capabilities: metabolic processes such as lipolysis and glycogenolysis; hormone
      secretion; the permeability of ion channels; gene expression; cell proliferation
      and survival. Indeed, it can be argued that the discovery of cyclic AMP initiated
      the study of intracellular signaling pathways, a major focus of contemporary
      biomedical inquiry. This review presents relevant details of Sutherland's career;
      summarizes key contributions of his mentors, Carl and Gerti Cori, to the
      knowledge of glycogen metabolism (contributions that were the foundation for his
      own research); describes the experiments that led to his identification,
      isolation, and characterization of cyclic AMP; assesses the significance of his
      work; and considers some aspects of the impact of cyclic nucleotide research on
      clinical medicine.

PMID- 22643762
TI  - Should direct-to-consumer personalized genomic medicine remain unregulated?: a
      rebuttal of the defenses.
AB  - Direct-to-consumer personalized genomic medicine has recently grown into a small
      industry that sells mail-order DNA sample kits and then provides disease risk
      assessments, typically based upon results from genome-trait association studies.
      The companies selling these services have been largely exempted from FDA
      regulation in the United States. Testing kit companies and their supporters have
      defended the industry's unregulated status using two arguments. First, defenders
      have argued that mere absence of harm is all that must be proved for mail-order
      tests to be acceptable. Second, defenders of mail-order testing have argued that
      there is an individual right to the tests' information. This article rebuts these
      arguments. The article demonstrates that the direct-to-consumer market has
      resulted in the sidelining of clinical utility (medical value to patients),
      leading to the development of certain mail-order tests that do not promote
      customers' interests and to defenders' downplaying of a potentially damaging
      empirical study of mail-order genomic testing's effects on consumers. The article
      also shows that the notion of an individual right to these tests rests on a
      flawed reading of the key service provided by mail-order companies, which is the
      provision of medical interpretations, not simply genetic information. Absent
      these two justifications, there is no reason to exempt direct-to-consumer
      personalized genomic medicine from stringent federal oversight.

PMID- 22643763
TI  - Reconsidering detached concern: the case of intensive-care nurses.
AB  - The concept of detached concern, as proposed by Renee Fox in Experiment Perilous
      (1959), is often used in the literature today in a way she did not intend. Rather
      than viewing detachment and concern as dualities, scholars frequently conceive of
      them as dichotomous, emphasizing detachment over concern. We reconsider detached
      concern here through the stories 37 intensive-care nurses told about their most
      memorable patients. While many described efforts to keep emotionally distant from
      patients, they also expressed concern for patients they felt connected to,
      especially those who were a first for them, who were long-term primary patients,
      who surprised them, or who died. The care nurses provide for these patients is
      shaped sociologically by their training and institutional contexts and is not an
      aberration or indicative of their losing control of their feelings. Instead, it
      is evidence of the dual nature of detached concern and of the importance of
      viewing the concept as describing more than emotional detachment.

PMID- 22643764
TI  - Clinical expertise and the limits of explicit knowledge.
AB  - This article questions the view that medical decision-making can be reduced to a
      series of explicit rules, adherence to which will necessarily improve outcomes.
      Instead, it attempts to rehabilitate the concepts of clinical expertise and
      clinical experience, arguing that medicine, like other areas of expertise,
      depends on forms of implicit knowledge that can only be acquired through years of
      experience. Recent research on "fast and frugal" heuristics in medical decision
      making suggest that statistical techniques are not necessarily superior to
      clinician judgment. Since clinical decisions are made on individual patients
      within the constraint of limited information, they must rest on clinical
      expertise and not clinical rules.

PMID- 22643765
TI  - Do no harm: a case in point.
AB  - The principle of avoiding harm, though still cited here and there in the
      literature, is regarded by many as a bit of antiquarianism with no relevance to
      actual medical practice and decision-making. But while treatment necessarily
      entails trading off risks against benefits, it is not so easy to defend harm
      caused in the name of prevention. Drugs intended for preventive use by the
      general population must meet high standards of safety-that is, they should not
      harm. This principle came to the fore in a recent meeting of an FDA Advisory
      Committee tasked with deciding whether or not to recommend two drugs for the
      prevention of prostate cancer. As the transcript of this charged meeting shows,
      the principle of avoiding harm is far from an inert doctrine without application
      to medicine.

PMID- 22643766
TI  - Chinese medical ward: an American's observations.
AB  - Physicians base their practices on scientific knowledge that varies little from
      one country to another, but their experience and their careers are shaped by the
      culture in which they live and work. This essay casts light on medical practice
      in mainland China, based on three months of field work with an elite group of
      physicians at a tertiary academic medical center in summer 2009. It is a story of
      a diverse group of Chinese professionals navigating a demanding profession, and
      of the foreign college student on whom they left an indelible impact. Many of the
      normative features of the Chinese medical profession-its chain of command,
      commitment to medical ethics, and scientific orientation-are highly comparable to
      the working lives of American physicians.

PMID- 22643767
TI  - Near infrared luminescence of gold nanoclusters affected by the bonding of 1,4
      dithiolate durene and monothiolate phenylethanethiolate.
AB  - The impacts of Au-thiolate bonding on the near infrared (IR) luminescence of Au
      nanoclusters are studied by designing two types of monolayer reactions. Firstly,
      1,4-dithiol durene (durene-DT) is reacted with Au(25) monolayer protected
      clusters (MPCs) stabilized by phenylethanethiolate (PhC2S) ligands. Upon the
      addition of durene-DT, the near IR luminescence of Au MPCs intensifies while the
      well-defined absorbance bands diminish. The optical transition is associated with
      the ligand exchange process monitored by proton NMR. In the second approach,
      PhC2S monothiols are reacted with durene-DT stabilized Au nanoclusters (DTCs).
      The addition of PhC2S to the Au DTCs induces the gradual decrease of the near IR
      luminescence. Mass spectrometry and NMR analysis reveal similar final products of
      mixed thiolate Au nanoclusters from both reactions. The results suggest that the
      1,4-dithiolate-Au bonding interaction is a promising factor to further enhance
      the near IR luminescence of Au nanoclusters for biomedical applications.

PMID- 22643768
TI  - Nodular prurigo of the vulva.

PMID- 22643781
TI  - Participatory design and research: pathways to healthy communities and racial
      equity.

PMID- 22643782
TI  - Cultures, collaboratives, and capabilities: the richness of Asian American,
      Native Hawaiian, and Pacific Islander CBPR.

PMID- 22643783
TI  - A community-based participatory approach to a hepatitis B intervention for Korean
      Americans.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection and liver cancer are severe health
      problems among Korean Americans. Most Korean Americans are neither screened nor
      vaccinated against HBV owing to substantial access barriers. OBJECTIVES: The
      primary objective of this article is to highlight how our team of academic
      researchers and community partners worked together to apply a community-based
      participatory research (CBPR) approach to developing, implementing, and
      evaluating a culturally appropriate, church-based HBV screening and vaccination
      intervention program for Korean Americans. METHODS: Guided by CBPR, multiple
      strategies were used to form academic-community partnerships in the development
      and implementation of the culturally appropriate HBV intervention program in the
      Korean-American community. These include the formation of a community advisory
      board (CAB) and adoption of CBPR principles, community needs assessment,
      development and evaluation of the pilot intervention program, and the full-scale
      community controlled trial. RESULTS: The pilot intervention results indicated
      significant increases in screening and vaccination rates in the intervention
      group compared with the control group. With the success of the partnership and
      pilot study, Korean church leaders, CAB members, and researchers are currently co
      leading a full-scale intervention study to further evaluate the effectiveness of
      the intervention program. CONCLUSION: The current study highlights the role and
      contributions of multiple partners through five phases and discusses the
      challenges and lessons learned for how to sustain intervention programs by
      emphasizing common vision, trust development, shared recognition, capacity
      building, long-term commitments to partnership building, and balance between
      science and community needs.

PMID- 22643784
TI  - Project CHARGE: building an urban health policy advocacy community.
AB  - BACKGROUND: The Coalition for Health Access to Reach Greater Equity (Project
      CHARGE) is a health policy advocacy coalition devoted to improving healthcare
      access for Asian Americans in New York City. OBJECTIVES: This paper discusses
      Project CHARGE's strategies for building a successful coalition. METHODS:
      Findings are based on evaluation data from field observations and surveys of
      Coalition representatives. LESSONS LEARNED: (1) Health policy coalitions can gain
      strength by recruiting from a wider range of organizations; maintaining a diverse
      coalition requires developing strong relationships among members. (2) Locally
      focused health policy coalitions should consider modifying course if needed to
      respond to policy developments at other governmental levels. (3) Health service
      providers can help to sustain policy advocacy activities if sufficient training
      is provided to develop them into policy advocates. (4) Early successes need to be
      planned to galvanize Coalition members. CONCLUSIONS: Aiming to build a policy
      advocacy "community" may help to ensure that advocacy continues even when funding
      is scarce.

PMID- 22643785
TI  - Pathway out of poverty: a values-based college-community partnership to improve
      long-term outcomes of underrepresented students.
AB  - BACKGROUND: Native Hawaiians, representing 25% of Hawai'i's population, suffer
      socioeconomic and health strains as evidenced by overrepresentation in low-wage
      jobs without health insurance and a higher prevalence of chronic disease compared
      with Hawai'i's other ethnic groups. Native Hawaiians are more likely to attend
      community colleges than 4-year colleges and have high dropout rates. OBJECTIVE:
      To describe a culturally relevant, community-based action research approach to
      build a program to keep Hawaiians in college to advance career options and
      improve long-term health and socioeconomic outcomes. METHODS: Culturally relevant
      approaches that depended on participation from a variety of community partners
      were used to evaluate needs and design interventions. RESULTS: The Pathway Out of
      Poverty Program uses Hawaiian values and traditions of healthy living to lead
      students through a nursing pathway from nurse aide (NA) to licensed practical
      nurse (LPN) to registered nurse (RN), with inherent increases in wage-earning
      potential. In the first 3.5 years, 150 students enrolled in NA training, and 135
      students (90%) graduated and were certified. Of the 135, 77 (57%) transitioned to
      higher education and 79% transitioned to jobs that offered health insurance (20%
      were in both groups). Of the 77 entering higher education, 33 (43%) aimed for a
      degree in nursing. Students expressed growing interest in health promotion for
      themselves, family members, and others. CONCLUSION: Community partners were key
      to developing a successful community college-based Pathway Program to help
      marginalized and other underrepresented students move from low-wage to living
      wage jobs and improve their long-term health outcomes.

PMID- 22643786
TI  - Improving Asian American, Native Hawaiian, and Pacific Islander health: national
      organizations leading community research initiatives.
AB  - BACKGROUND: Functionally, many CBPR projects operate through a model of academic
      partners providing research expertise and community partners playing a supporting
      role. OBJECTIVES: To demonstrate how national umbrella organizations deeply
      rooted in communities, cognizant of community needs, and drawing on the insights
      and assets of community partners, can lead efforts to address health disparities
      affecting their constituents through research. METHODS: Case studies of two Asian
      American, Native Hawaiian, and Pacific Islander national organizations. RESULTS:
      Strategically engaging a diverse range of partners and securing flexible funding
      mechanisms that support research were important facilitators. Main challenges
      included limited interest of local community organizations whose primary missions
      as service or health care providers may deprioritize research. CONCLUSIONS:
      Efforts to make research relevant to the work of community partners and to
      instill the value of research in community partners, as well as flexible funding
      mechanisms, may help to promote community-driven research.

PMID- 22643787
TI  - Developing the community empowered research training program: building research
      capacity for community-initiated and community-driven research.
AB  - Health promotion practice research conducted by or in partnership with community
      based organizations (CBOs) serving Asian Americans, Native Hawaiians, and Pacific
      Islanders (AA and NHPI) can address health disparities. Few CBOs have the tools
      to integrate or initiate research into their programmatic agenda. The New York
      University (NYU) Center for the Study of Asian American Health (CSAAH) and the
      Asian & Pacific Islander American Health Forum (APIAHF) created a partnership
      with the goal to support CBO research infrastructure development by creating the
      Community Empowered Research Training (CERT) program. METHODS: A survey was
      conducted and discussions held with CBO leaders representing AA and NHPI
      communities to inform the development of the CERT program. RESULTS: The majority
      of participants are engaged in service-related research and reported interest in
      building their research capacity. CBOs may require help reframing how data can be
      collected and used to better inform programmatic activities and to address health
      disparities facing AA and NHPI communities. CONCLUSIONS: CBOs possess both an
      interest in and access to local knowledge that can inform health priorities.
      Findings have been applied to the CERT program to build capacity to support
      community-initiated/driven research to address health disparities affecting AAs
      and NHPIs.

PMID- 22643788
TI  - Community-based participatory research approach to evidence-based research:
      lessons from the Pacific Islander American Health Study.
AB  - OBJECTIVES: Reports on the challenges and lessons learned from the Pacific Island
      American Health Study engagement with community-based organizations (CBOs) and
      faith-based organizations (FBOs) in Pacific Islander (PI) communities and
      mechanisms to facilitate the collection of robust data. METHODS: Academic
      community partnership building was achieved with PI CBOs and FBOs. Focus group
      meetings were organized to plan various aspects of the study, develop
      questionnaire themes and protocols for survey, assist with the interviewer
      recruitment process, and strategize data dissemination plan. LESSONS LEARNED: The
      PIA-HS represents a model for overcoming challenges in data collection among
      small understudied populations. FBOs represent a valuable resource for community
      based participatory research (CBPR) data collection and for effective
      interventions. CONCLUSION: The study methodology can be replicated for other
      racial/ethnic groups with high levels of religiosity combined with concentrated
      levels of residential clustering. Expansion of the Pacific Islander American
      Health Study (PIA-HS) to include other PI subgroups is encouraged.

PMID- 22643789
TI  - Asian American health research: what community agencies on the front line need to
      know.
AB  - To be most effective, community agencies working to improve the health of Asian
      Americans require a deep knowledge of their target community and have evidence
      based programs and policies at their disposal. Unfortunately, Asian American
      health research is still emerging. For some health promotion curricula that have
      proven effective among general populations, there is no evidence that these
      curricula will be as effective among Asian American populations, particularly
      those with limited English proficiency. In addition, the effect of acculturation
      on health-seeking behaviors among Asian Americans is still poorly understood, but
      has a large bearing on looming health problems such as obesity and diabetes.
      Last, given that 30% of Asian Americans are of limited English proficiency, how
      does the cultural competency of the American health care system impact access to
      care among Asian Americans? These and other questions are key considerations in
      developing effective community health approaches for Asian Americans.

PMID- 22643791
TI  - Developing a proactive research agenda to advance nail salon worker health,
      safety, and rights.
AB  - THE PROBLEM: Nail salons represent a burgeoning industry with Vietnamese
      immigrant workers making up the majority. Workers routinely handle cosmetic
      products containing hazardous compounds, with implications for their health.
      PURPOSE OF ARTICLE: This paper describes how a collaborative of multiple
      organizations and community members collectively developed a proactive research
      agenda for salon worker health, safety, and rights during a pivotal
      multistakeholder convening, and advanced on such recommendations, including
      creating groundbreaking policy changes. KEY POINTS: Key recommendations included
      (1) creating a multidisciplinary research advisory committee, (2) conducting
      research on workplace exposures and long-term health impacts, (3) advocating for
      better governmental oversight of product manufacturers, and (4) identifying safer
      product alternatives via green chemistry, albeit with cost considerations to
      salon businesses. CONCLUSION: The participation of diverse stakeholders in the
      discussions allowed for cross-dialogue on a complex issue, helped to align
      different stakeholders as allies, and identified critical resources to addressing
      research gaps.

PMID- 22643792
TI  - Role of federal policy in building research infrastructure among emerging
      minorities: the Asian American experience.
AB  - PROBLEM: Considerable progress in Asian American health research has occurred
      over the last two decades. However, greater and sustained federal support is
      needed for reducing health disparities in Asian American communities. PURPOSE OF
      THE ARTICLE: This paper reviews federal policies that support infrastructure to
      conduct minority health research and highlights one model for strengthening
      research capacity and infrastructure in Asian American communities. KEY POINTS:
      Research center infrastructures can play a significant role in addressing
      pipeline/workforce challenges, fostering campus-community research
      collaborations, engaging communities in health, disseminating evidence-based
      strategies and health information, and policy development. CONCLUSION: Research
      centers provide the capacity needed for academic institutions and communities to
      work together synergistically in achieving the goal to reduce health disparities
      in the Asian American community. Policies that support the development of
      concentrated and targeted research for Asian Americans must continue so that
      these centers will reach their full potential.

PMID- 22643793
TI  - Bridging academic-legislative divides: models of policy-relevant health research
      and practice by the University of California.
AB  - PROBLEM: This paper argues that it is necessary to strengthen Asian American,
      Native Hawaiian, and Pacific Islander (AA and NHPI) community-based participatory
      research (CBPR) models that integrate a health policy agenda through dynamic
      legislative partnerships. PURPOSE: We utilize a case study approach and examine
      three health research partnership models that impact legislative design and
      action: The California Program on Access to Care (CPAC), the California Health
      Benefits Review Program (CHBRP), and the University of California Asian American
      and Pacific Islander Policy Multicampus Research Program (UC AAPI Policy MRP).
      KEY POINTS: In-depth examination reveals the difficulties of engaging in research
      that collaborates with multiple parties simultaneously and the specific benefits
      and challenges in each case. CONCLUSIONS: New directions are needed to deepen
      legislative engagement potential in CBPR and the translation of policy research
      that considers the health of all AA and NHPI communities.

PMID- 22643794
TI  - Developing a culturally based cardiac rehabilitation program: the HELA study.
AB  - BACKGROUND: Heart disease disproportionately affects Native Hawaiians and other
      Pacific people. In response, researchers proposed and communities endorsed,
      developing a cardiac rehabilitation (CR) program based on the hula, a Native
      Hawaiian dance form. The utilization of cultural practices in health
      interventions can improve outcomes and increase enrollment and retention, but
      requires sensitivity and understanding. OBJECTIVE: This paper provides the
      conceptual framework and methods used for integration of multiple communities'
      perspectives to inform the design of a hula-based CR intervention. METHODS:
      Specific strategies and processes were established to ensure the equity of
      scientific-clinical and patient- cultural knowledge and perspectives. Multiple
      methods were used and a flow diagram defined steps for the intervention
      development. RESULTS: Patient and cultural consultations provided information
      about the multidimensional benefits of hula and its use in a CR intervention.
      Clinical and scientific consultations provided specific guidelines for exercise
      prescription and patient monitoring. Integrating findings from all consultations
      identified important direction and requirements. CONCLUSIONS: Community-based
      participatory research (CBPR) principles guided a complex collaboration of
      multiple communities; although time consuming, inclusive consultations provided
      valuable information and relationships.

PMID- 22643795
TI  - Nonunion of fibula: a systematic review.
AB  - PURPOSE: The purpose of this systematic review was to analyse the available
      evidence regarding nonunions of the fibula. We focussed on the incidence, risk
      factors, evaluation, and treatment modalities for fibular nonunions as evident in
      the current literature and propose a treatment algorithm. METHODS: This was an
      Institutional Review Board (IRB) exempt study performed at a level one trauma
      centre. We systematically reviewed the published evidence on fibular nonunion or
      delayed union from 1950 to February, 2011. RESULTS: Twelve articles were included
      in this systematic review. In summary, nonunion of the fibula is becoming
      increasingly more common in association with intramedullary nailing of
      concomitant tibial shaft fractures. A treatment algorithm for nonunion of the
      fibula has been proposed. CONCLUSIONS: The suspicion for nonunion of the fibula
      should be heightened in lower leg fractures if the patient is symptomatic, and
      the progression of healing is not as expected. Ideally, prospective, multicentre
      studies would be performed to provide more rigorous data on the incidence, risk
      factors, and optimum treatment.

PMID- 22643796
TI  - Expression of vascular endothelial growth factor in Ewing's sarcoma.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is the most potent stimulator
      of angiogenesis. The aim of this study was to evaluate the role of serum VEGF as
      a diagnostic, predictive and prognostic marker in Ewing's sarcoma. METHODS:
      Patients with histopathologically proven diagnosis of Ewing's sarcoma without
      prior chemotherapy or radiotherapy were invited to take part in the study. Pre
      chemotherapy, post-chemotherapy and post-surgery blood samples were collected for
      analysis of serum VEGF levels. Blood samples from ten sex- and age-matched
      healthy volunteers were collected for estimation of VEGF levels to act as
      control. Human VEGF Elisa kit (Bender Medsystem, Austria) was used to assess the
      serum VEGF levels. RESULTS: A total of nine cases of Ewing's sarcoma were
      included in the study. Mean age in the group was 12.44 years (range, seven to 18
      years). Mean and median serums VEGF level in the study population were 4,547.78
      pg/ml and 3,780.00 pg/ml, respectively. Ten age- and sex-matched healthy
      volunteers were selected as controls. No significant correlation was obtained
      between serum VEGF, age, sex and tumour size. Mean serum VEGF was significantly
      raised in the study group as compared to controls (p = 0.001). We observed a
      significant decline in serum VEGF level following neoadjuvant chemotherapy (p =
      0.008). No correlation could be established between serum VEGF level pulmonary
      metastasis and overall survival. CONCLUSION: Serum VEGF might have a role as a
      diagnostic and predictive marker in patients with Ewing's sarcoma.

PMID- 22643797
TI  - A new technique in double-bundle anterior cruciate ligament reconstruction: some
      concerns.

PMID- 22643798
TI  - Patients with no functional improvement after total knee arthroplasty show
      different kinematics.
AB  - PURPOSE: As many as 20 % of all patients following total knee arthroplasty are
      not satisfied with the result. Rotational alignment is one factor thought to
      affect clinical outcome. The purpose of this study was to assess relationships
      between prosthesis rotational alignment, function score and knee kinematics after
      TKA. METHODS: In 80 patients a cemented, unconstrained, cruciate-retaining TKA
      with a rotating platform was implanted. Rotational alignment was measured using
      CT-scans. Kinematics was assessed using fluoroscopy images. RESULTS: Seventy
      three patients were available for follow-up after two years. Nine patients had
      more than 10 degrees  rotational mismatch between the femoral and tibial
      component in the postoperative CT scans. These patients showed significantly
      worse results in the function score. While the normal patients with less than 10
      degrees  rotational mismatch improved from a mean pre-operative 55 points to a
      mean 71 points at follow-up, the group with more than 10 degrees  mismatch
      deteriorated from a mean 60 points pre-operatively to a mean 57 points at follow
      up. The pattern of motion during passive flexion from approximately 0 degrees  to
      120 degrees  was quite different. While external rotation steadily increased with
      knee flexion in the normal group, there was internal rotation between 30 degrees 
      and 80 degrees  of flexion in the group with more than 10 degrees  rotational
      mismatch. CONCLUSION: Rotational mismatch between femoral and tibial components
      exceeding 10 degrees  resulted in different kinematics after TKA. It might
      contribute to worse clinical results observed in those patients and should
      therefore be avoided.

PMID- 22643799
TI  - Effect of nerve growth factor and its transforming tyrosine kinase protein and
      low-affinity nerve growth factor receptors on apoptosis of notochordal cells.
AB  - PURPOSE: The disappearance of notochordal cells by apoptosis is thought to be the
      starting point of intervertebral disc degeneration. The aim of this study was to
      determine the apoptotic pathway of notochordal cells as well as the anti
      apoptotic potential of caspase inhibitors. METHODS: Rat notochordal cells were
      isolated, cultured, and placed in either 0 % (apoptosis-promoting condition) or
      10 % (normal control) foetal bovine serum (FBS). We identified and quantified
      apoptotic cell deaths and caspase activities. In addition, we examined the cells
      for expression of nerve growth factor (NGF) and its two receptors--TrkA (survival
      signal) and p75 (apoptotic signal)--and downstream pathways. Finally, we analysed
      the degree of anti-apoptotic effects of caspase inhibitors on the cells. RESULTS:
      The apoptotic rate and expressions of caspase-8 (extrinsic pathway), -9
      (intrinsic pathway), and -3 (common executioner) of notochordal cells were
      increased in 0 % FBS compared with those in 10 % FBS. Expressions of NGF, p75
      receptor and JNK downstream pathways were also increased in 0 % FBS. In contrast,
      expressions of the TrkA receptor and Akt and MAPK downstream pathways were
      decreased in 0 % FBS. Pancaspase, capase-9 and capase-8 inhibitors significantly
      reduced apoptotic cell death. CONCLUSIONS: Our results suggest that notochordal
      cells undergo apoptosis through both the intrinsic and extrinsic pathways by
      activation of NGF, p75 receptor, and the JNK downstream pathway. We also found
      that apoptosis of notochordal cells can be attenuated by caspase inhibitors.
      Caspase inhibitors may play a therapeutic role in delaying the starting point of
      disc degeneration that is due to inappropriate or premature excessive apoptosis
      of notochordal cells.

PMID- 22643800
TI  - Tuberculous extensor tenosynovitis of the hand.
AB  - Tuberculous tenosynovitis is a rare manifestation of extrapulmonary tuberculosis
      (Tb), especially if solely the dorsal hand compartment is affected. In this
      report, we present the medical history of an immuno-competent 32-year-old man
      presented with a painful swelling of the right dorsal wrist. Initial inflammation
      onset had occurred 6 months before he consulted our service, resulting in
      consultation of several physicians and extensive diagnostic procedures without
      gaining a specific diagnosis. Finally, after extensive diagnostic tests, a
      tenosynovectomy was performed and tuberculosis-induced extensor tenosynovitis was
      detected. The diagnosis was established by positive histology, repeated specific
      PCR and T-SPOT.TB. Tuberculous tenosynovitis can easily be overlooked as a cause
      of chronic tenosynovitis particularly in immunocompetent young people lacking any
      risk factors.

PMID- 22643801
TI  - Pathway-controlled fast-track rehabilitation after total knee arthroplasty: a
      randomized prospective clinical study evaluating the recovery pattern, drug
      consumption, and length of stay.
AB  - PURPOSE: To investigate fast-track rehabilitation concept in terms of a
      measurable effect on the early recovery after total knee arthroplasty (TKA).
      METHODS: This was an open, randomized, prospective clinical study, comparing the
      fast-track rehabilitation--a pathway-controlled early recovery program (Joint
      Care((r)))--with standard postoperative rehabilitation care, after TKA. Overall,
      147 patients had TKA (N = 74 fast-track rehabilitation, N = 73 standard
      rehabilitation). The fast-track rehabilitation patients received a group therapy,
      early mobilization (same day as surgery) and 1:1 physiotherapy (2 h/day). Patient
      monitoring occurred over 3 months (1 pre- and 4 post-operative visits). The
      standard rehabilitation group received individual postoperative care according to
      the existing protocol, with 1:1 physiotherapy (1 h/day). The cumulative American
      Knee Society Score (AKSS) was the primary evaluation variable, used to detect
      changes in joint function and perception of pain. The secondary evaluation
      variables were WOMAC index score, analgesic drug consumption, length of stay
      (LOS), and safety. RESULTS: After TKA, patients in the fast-track rehabilitation
      group showed enhanced recovery compared with the standard rehabilitation group,
      as based on the differences between the groups for the cumulative AKSS (p =
      0.0003), WOMAC index score (<0.0001), reduced intake of concomitant analgesic
      drugs, reduced LOS (6.75 vs. 13.20 days, p < 0001), and lower number of adverse
      events. CONCLUSION: For TKA, implementation of pathway-controlled fast-track
      rehabilitation is achievable and beneficial as based on the AKSS and WOMAC score,
      reduced intake of analgesic drugs, and reduced LOS.

PMID- 22643802
TI  - Comment on "Integrated FDG-PET-CT: its role in the assessment of bone and soft
      tissue tumors" (Arch Orthop Trauma Surg. 2010 Jul; 130(7):819-27).

PMID- 22643803
TI  - Marginal contribution of UKS- versus TKA in varus arthritis of the knee.
AB  - BACKGROUND: In recent years, decisions regarding the treatment of individual
      patients have increasingly been affected by economic considerations. The G-DRG
      system reimburses sledge endoprosthetic implantations at a much lower rate than
      surface replacements and at significantly different cost weights (CW). Therefore,
      when only G-DRG payments are considered, TKA produces higher gains. Taking only
      these revenues alone into consideration, however, does not provide the basis of
      an economically sound decision-making process. The target of this research was to
      present a comparison between variable costs of the two procedures. METHODS: The
      mean cost and performance data of 28 Endo-Modell (Link company) sledge
      implantations (UKS) and of 85 NexGen CR surface replacement total knee
      arthroplasties (TKA; Zimmer company) were compared in 2007. RESULTS: From the
      perspective of the hospital, UKS treatment is of greater economic advantage when
      the medical indication is given. In preferring UKS marginal contribution can be
      improved, and although the relative weighting is comparatively low, the costs are
      significantly lower than in a comparative analysis of TKA. Based on the length of
      stay required for each procedure the average daily CW for UKS can be calculated
      as 0.1728, while being 0.1955 for TKA. The earlier release of the first patient
      results in another patient being admitted 1.5 days earlier and thus an increase
      in case mix. Meanwhile, the case-mix index and the costs of care per case
      decrease ceteris paribus. CONCLUSION: Assuming the correct medical indication,
      the hospital seeking to maximize its marginal contribution would be wise to
      select sledge endoprosthesis implantation. Considering the economic perspective
      of gains and costs, the assumption that TKA is advantageous could not be
      confirmed in the present study.

PMID- 22643804
TI  - Axially vascularized bone substitutes: a systematic review of literature and
      presentation of a novel model.
AB  - INTRODUCTION: The creation of axially vascularized bone substitutes (AVBS) has
      been successfully demonstrated in several animal models. One prototypical
      indication is bone replacement in patients with previously irradiated defect
      sites, such as in the mandibular region. The downside of current clinical
      practice, when free fibular or scapular grafts are used, is the creation of
      significant donor site morbidity. METHODS: Based on our previous experiments, we
      extended the creation of an arterio-venous loop to generate vascularized bone
      substitutes to a new defect model in the goat mandibula. In this report, we
      review the literature regarding different models for axially vascularized bone
      substitutes and present a novel model demonstrating the feasibility of combining
      this model with synthetic porous scaffold materials and biological tissue
      adhesives to grow cells and tissue. RESULTS: We were able to show the principal
      possibility to generate axially vascularized bony substitutes in vivo in goat
      mandibular defects harnessing the regenerative capacity of the living organism
      and completely avoiding donor site morbidity. CONCLUSION: From our findings, we
      conclude that this novel model may well offer new perspectives for orthopedic and
      traumatic bone defects that might benefit from the reduction of donor site
      morbidity.

PMID- 22643805
TI  - Inherited thrombophilia may be a causative factor for osteonecrosis of femoral
      head in male patients with developmental dysplasia of the hip: a case series.
AB  - PURPOSE: The aim of this case series was to assess the effect of two common
      causes of inherited thrombophilia, factor V Leiden (FVL) and prothrombin mutation
      (PTM) on the development of osteonecrosis of the femoral head (ONFH) following
      the treatment of developmental dysplasia of the hip (DDH). METHODS: FVL and PTM
      analysis of 58 patients (45 females and 13 males; mean age 12.2 years) with ONFH
      due to DDH treatment was done. RESULTS: Rate of inherited thrombophilia (FVL plus
      PTM) was 15.5 %. Inherited thrombophilia was nearly four times higher in male
      patients than in female patients and this difference was mainly due to FVL (P <
      0.05). This finding was against the common belief that, coagulation abnormalities
      were equally distributed across the sexes in normal population. Rates of overall
      inherited thrombophilia, FVL and PTM were not correlated with the type of ONFH (P
      > 0.05). CONCLUSION: Hereditary thrombophilia, especially FVL, may be one of the
      causative factors for the development of ONFH following DDH treatment in male
      patients. Further prospective, controlled studies are needed to undoubtedly
      enlighten this issue.

PMID- 22643806
TI  - 23-G pars plana vitrectomy, lensectomy, and artisan IOL implantation for the
      management of nontraumatic ectopia lentis: a new iris enclavation technique for
      iris claw lens.

PMID- 22643822
TI  - Exploring the intermediates of photochemical CO2 reduction: reaction of
      Re(dmb)(CO)3 COOH with CO2.
AB  - We have investigated the reaction of Re(dmb)(CO)(3)COOH with CO(2) using density
      functional theory, and propose a mechanism for the production of CO. This
      mechanism supports the role of Re(dmb)(CO)(3)COOH as a key intermediate in the
      formation of CO. Our new experimental work supports the proposed scheme.

PMID- 22643823
TI  - Balancing riparian management and river recreation: methods and applications for
      exploring floater behavior and their interaction with large wood.
AB  - River managers are tasked with meeting both ecological and human needs. In the
      Puget Sound lowland, riparian management often includes placing or allowing the
      presence of large wood to stabilize riverbanks and enhance salmon habitat.
      Although this practice benefits humans by protecting infrastructure and natural
      resources, it is unclear how such practices interact with an additional human
      interest, recreation. Furthermore, we were unable to find studies that describe
      how an agency can go about researching the interaction between recreation and
      large wood management practices. This study tested methods for describing and
      estimating the number of river floaters, where they float in relationship to
      river projects, the risks they take while floating, and their perceptions of
      large wood in the river. Selecting a high-use suburban river in Washington State,
      we used riverside observations, interviews, and an infrared counter to gather
      data in the summer of 2010. Statistical analyses provided general characteristics
      of users, trends in engaging in risky behaviors, and estimates of use for the
      entire season and on the busiest day. Data mapping with GIS presented the density
      of use along the river and frequency of use of specific float routes. Finally,
      qualitative analysis of interviews clarified floaters' perspectives of large
      wood. To address the multiple mandates of river managers, it is important to
      understand recreation users, the factors that could be putting them at risk, and
      how the actual users perceive large wood in the river. This study demonstrates
      methods for scientifically gathering such information and applying it when making
      riparian management decisions.

PMID- 22643824
TI  - Double-crested cormorant (Phalacrocorax auritus) nesting effects on understory
      composition and diversity on island ecosystems in Lake Erie.
AB  - The context for this study is the management concerns over the severity and
      extent of the impact of cormorants on island flora in the recent past on Lake
      Erie islands. Accordingly, this study sought to quantify the nesting colonies'
      influence on coarse woody litter and how nest densities and litter depth may
      influence the herbaceous layer, the seed bank composition and viability across
      the extent of three Lake Erie islands. The data for this study were collected
      from 2004 to 2008 on East Sister Island and Middle Island using two main
      strategies. First, herbaceous layer surveys, cormorant nest counts, soil seed
      bank cores, and litter depth measurements were executed using a plotless-point
      quarter method to test island-wide impacts from nesting activities (data were
      also collected on a third island, West Sister Island as a reference for the other
      two islands). Secondly, a sub-sample of the entire plot set was examined in
      particularly high nesting density areas for two islands (Middle Island and East
      Sister Island). Kruskal-Wallis tests indicated that there are subtle changes in
      the herbaceous diversity (total, native and exotic) and seed bank composition
      across the islands. The sub sample set of the plots demonstrated that
      Phalacrocorax auritus nest density does influence litter depth, herbaceous
      species abundance and diversity. Cormorant nesting pressures are restricted to
      areas of high nesting pressures and competition. However, there remains a risk to
      the interior herbaceous layer of the island if the effects of nesting pressures
      at the edges advance inward from this perimeter.

PMID- 22643825
TI  - Pregnancy outcomes in women with Ebstein's anomaly.
AB  - OBJECTIVES: To evaluate whether women with Ebstein's anomaly can tolerate
      pregnancy and whether the perinatal outcomes are influenced by the severity of
      Ebstein's anomaly. METHODS: Data of four women with Ebstein's anomaly delivered
      in our unit were collected and analyzed retrospectively. RESULTS: (1) Two women
      with Ebstein's anomaly had uneventful pregnancies, cesarean section and
      puerperium. (2) The patient with the most serious Ebstein's anomaly (with central
      cyanosis and clubbing) had an episode of paroxysmal ventricular tachycardia and
      spontaneous cardioversion to sinus rhythm on day 4 postpartum. She developed
      intracerebral hemorrhage on day 25 postpartum. (3) One of them suffered from
      atrial flutter on 38 + 3 weeks of gestation which was restored to sinus rhythm
      after being treated with verapamil and remained stable afterward. (4) All
      neonatal birth weights were more than 2,500 g, and all neonatal Apgar scores were
      10 at 1 min. (5) The gestational age at delivery of our cases was from week 36 +
      4 to week 38 + 4. The mean duration of follow-up was 56 days postpartum.
      CONCLUSIONS: (1) The clinical features of pregnant women with Ebstein's anomaly
      vary. They might have good perinatal outcomes when given appropriate treatment.
      (2) Those with cyanosis should be given more attention, as they can have more
      complications during pregnancy, delivery and puerperium. (3) All women with
      Ebstein's anomaly should be offered fetal echocardiography during pregnancy. (4)
      Vaginal delivery is advised for most cases with Ebstein's anomaly.

PMID- 22643826
TI  - Abdominal colposuspension with the use of tension-free tape at the lateral
      abdominal wall: a novel technique.
AB  - INTRODUCTION: The aim of this study was to present a novel technique for the
      female pelvic organ prolapsed, an abdominal colpopexy at the lateral abdominal
      wall (ACLAW) using a tension-free tape and to compare it with the gold standard,
      the abdominal sacrocolpopexy (ASC). MATERIALS AND METHODS: A retrospective
      comparative study was conducted consisting of 38 patients who underwent ACLAW and
      40 patients who underwent ASC during the period 2007-2009. POP-Q data as well as
      PISQ-12 and POPDI-6 score values were recorded during a mean follow-up of 26.71
      and 23.52 months for ACLAW and ASC groups, respectively. Parameters like
      operative time, blood loss and hospital stay time were evaluated as well.
      RESULTS: Except the 6-month point, anatomical outcome in terms of C point values
      and total vaginal length was comparable. Both score analyses did not demonstrate
      statistically significant differences between the groups. The novel technique was
      proved very much shorter (30 +/- 10.2 vs. 125.93 +/- 15.42 min, p < 0.001) and
      less hemorrhagic (1.68 +/- 0.79 vs. 2.22 +/- 1.08 g/dl reduction in hemoglobin
      level, postoperatively) than the traditional sacrocolpopexy. Hospital stay time
      did not demonstrate significant difference. CONCLUSIONS: Based on the study
      results, ACLAW, a technique much easier and shorter than the traditional
      abdominal colpopexy results in comparable outcomes.

PMID- 22643828
TI  - Risk and prognosis of inguinal hernia in relation to occupational mechanical
      exposures--a systematic review of the epidemiologic evidence.
AB  - OBJECTIVES: The aim of this review was to evaluate the epidemiologic evidence for
      (i) a causal effect of occupational mechanical exposures on incidence of inguinal
      hernia, and (ii) a prognostic effect of such exposures on hernia recurrence and
      persistent pain after inguinal hernia repair. METHODS: We performed a literature
      search in Medline, Embase, and Web of Science up to 3 November 2011. Central
      information was extracted from included studies, and strengths and limitations
      were discussed. RESULTS: All 23 included studies focused on effects of (work)
      activities that hardly reflected specific occupational risk factors. Eight
      studies provided information on risk by occupation or occupational activities.
      Increased risk was reported in six studies, but inflationary bias was likely. The
      negative findings in two studies might well be explained by bias towards the null
      due to crude exposure and/or outcome assessment. Three studies on single
      strenuous events primarily reflected patients' beliefs regarding risk factors.
      Information on prognosis with respect to recurrence was found in seven studies.
      The studies used crude exposure assessment, and two were also underpowered. Four
      suggested an increased risk. Six studies on prognosis with respect to persistent
      pain (one of which also concerned recurrence) were practically non-informative
      for the purpose of this review. CONCLUSIONS: There is insufficient epidemiologic
      evidence to draw meaningful conclusions about (i) the existence of causal
      associations between specific occupational mechanical exposures and the
      development of inguinal hernia, and (ii) the influence of these exposures on
      prognosis after inguinal hernia repair with respect to hernia recurrence and
      persistent pain.

PMID- 22643827
TI  - Novel therapeutic targets in the brain tumor microenvironment.
AB  - Glioblastoma (GBM), a highly malignant brain tumor of adults and children,
      diffusely invades within the non-neoplastic brain. Despite aggressive current
      therapeutic interventions, improved therapeutic strategies are greatly needed.
      Interactions between the tumor and constituents of its microenvironment are known
      to regulate malignancy, and heparan sulfate proteoglycans (HSPGs) are important
      as they bind diverse extracellular proteins, including growth factors and cell
      adhesion molecules, regulating the activity of several ligand-mediated signaling
      pathways. Recent work from our group described a mechanism by which GBM regulates
      PDGFR-alpha signaling via enzymatic alteration of heparan sulfate proteoglycans
      (HSPGs) in the extracellular microenvironment. Blocking tumor-induced alterations
      of HSPGs, which can be achieved by pharmacological strategies, would potentially
      inhibit multiple oncogenic signaling pathways in tumor cells and disrupt critical
      tumormicroenvironment interactions. Here we examine HSPGs and the enzymes that
      modify them in GBM. We compare their expression across tumor subtypes, their
      potential roles in oncogenesis, and their potential as novel therapeutic targets
      in GBM.

PMID- 22643829
TI  - Use of blood urea nitrogen, creatinine, interleukin-6, granulocyte-macrophage
      colony stimulating factor in combination to predict the severity and outcome of
      abdominal sepsis in rats.
AB  - OBJECTIVES: Accurate and timely diagnosis and prognosis of sepsis remain
      challenging. A combination of markers, as opposed to single ones, may improve the
      prognosis, and therefore survival. This study compared the effectiveness of
      routinely used biomarkers of sepsis alone and in combination for the prediction
      of outcome in rats with abdominal sepsis. METHODS: Rats were subjected to sepsis
      induced by cecal ligation and puncture (CLP). Seventeen biomarkers were detected
      12 h after the CLP. Correlation between the biomarkers and outcome of rats was
      analyzed; the correlated biomarkers were analyzed by logistic regression analysis
      and the area under the receiver operating characteristic (ROC) curve was computed
      to compare their performance in the prognosis of sepsis. RESULTS: A total of 49
      rats were eligible for analysis. Body temperature (T), blood urea nitrogen (BUN),
      creatinine (Cr), alanine aminotransferase (ALT), creatine kinase (CK),
      interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) levels after
      the CLP were negatively correlated with the survival outcome, while platelet
      count (PLT), high-mobility group box protein 1 (HMGB1) and granulocyte-macrophage
      colony stimulating factor (GM-CCF) were positively correlated with the survival
      outcome (P < 0.05). Levels of BUN, Cr, IL-6, and GM-CSF after the CLP were
      independent predictors of outcome according to conditional logistic regression.
      The sensitivity and specificity of the four selected biomarkers in combination
      for predicting sepsis outcome were better than single ones (P < 0.05).
      CONCLUSION: A combination of different biomarkers improves the diagnostic
      accuracy and is more effective in the prognosis of sepsis in rats. Use of BUN,
      Cr, IL-6, GM-CSF in combination to predict the severity and outcome in rats with
      abdominal sepsis exhibited acceptable diagnostic characteristics.

PMID- 22643830
TI  - Prevention of lung injury by Muc1 mucin in a mouse model of repetitive
      Pseudomonas aeruginosa  infection.
AB  - OBJECTIVE AND DESIGN: To determine whether repetitive airway Pseudomonas
      aeruginosa (Pa) infection results in lung inflammation and injury and, if so,
      whether these responses are affected by Muc1 mucin. Muc1 wild type (WT) and
      knockout (KO) mice were compared for body weights, lung inflammatory responses,
      and airspace enlargement using a chronic lung infection model system. MATERIALS:
      Mice were treated intranasally with Pa (10(7) CFU) on days 0, 4, 7 and 10. On day
      14, body weights, inflammatory cell numbers in bronchoalveolar lavage fluid
      (BALF), and airspace enlargement were measured. Differences in inflammatory
      responses between groups were statistically analyzed by the Student's t test and
      ANOVA. RESULTS: Muc1 WT mice exhibited mild degrees of both inflammation and
      airspace enlargement following repetitive airway Pa infection. However, Muc1 KO
      mice exhibited significantly decreased body weights, greater macrophage numbers
      in the BALF, and increased airspace enlargement compared with Muc1 WT mice.
      CONCLUSIONS: This is the first report demonstrating that Muc1 deficiency can lead
      to lung injury during chronic Pa infection in mice. These results suggest that
      MUC1 may play a crucial role in the resolution of inflammation during chronic
      respiratory infections and that MUC1 dysfunction likely contributes to the
      pathogenesis of chronic inflammatory respiratory disease.

PMID- 22643831
TI  - FLT3 in lineage specification and plasticity.
AB  - FLT3 is a receptor tyrosine kinase that is expressed in CD34+ hematopoietic stem/
      progenitor cells (HSPCs) and is important for both normal myeloid and lymphoid
      differentiation. FLT3 expression in Pax5 negative lymphoid precursors coincides
      with a window of multilineage differentiation potential in mice and humans.
      Recent work has shown that FLT3 activating mutations can collaborate with a Nup98
      HoxD13 mutation to induce an aggressive acute leukemia. The leukemic initiating
      population in this model displayed properties of both lymphoid and myeloid
      precursors, making it a useful tool to study the role of FLT3 in lineage
      plasticity. Through a variety of assays, the leukemic initiating population was
      shown to be restricted to myeloid differentiation, suggesting that the B-lineage
      properties in these cells are due to the priming of lymphoid transcription
      programs in multipotent progenitors rather than a true capacity for B-cell
      maturation. The development of an undifferentiated myeloid leukemia in this
      model, also has implications for the role of FLT3 in the inhibition of myeloid
      differentiation. Here we discuss the insights gained from this model.

PMID- 22643833
TI  - Anti-white spot syndrome virus activity of Ceriops tagal aqueous extract in giant
      tiger shrimp Penaeus monodon.
AB  - White spot syndrome virus (WSSV), the most contagious pathogen of cultured
      shrimp, causes mass mortality, leading to huge economic loss to the shrimp
      industry. The lack of effective therapeutic or prophylactic measures has
      aggravated the situation, necessitating the development of antiviral agents. With
      this objective, the antiviral activity in the aqueous extract of a mangrove plant
      Ceriops tagal in Penaeus monodon was evaluated. The Ceriops tagal aqueous extract
      (CTAE) was non-toxic to shrimps at 50 mg/ml when injected intramuscularly at a
      dosage of 10 MUL/animal (0.5 mg/animal) and showed a protective effect against
      WSSV at 30 mg/ml when mixed with WSSV suspension at a 1:1 ratio. When the extract
      was administered along with the diet and the animals were challenged orally,
      there was a dose-dependent increase in survival, culminating in 100 % survival at
      a concentration of 500 mg/kg body weight/day. Neither hypertrophied nuclei nor
      the viral envelope protein VP28 could be demonstrated in surviving shrimps using
      histology and indirect immunofluorescence histochemistry (IIFH), respectively. To
      elucidate the mode of action, the temporal expression of WSSV genes and shrimp
      immune genes, including antimicrobial peptides, was attempted. None of the viral
      genes were found to be expressed in shrimps that were fed with the extract and
      challenged or in those that were administered CTAE-exposed WSSV. The overall
      results suggest that the aqueous extract from C. tagal can protect P. monodon
      from white spot syndrome virus infection.

PMID- 22643832
TI  - Impaired volitional saccade control: first evidence for a new candidate
      endophenotype in obsessive-compulsive disorder.
AB  - Recent research suggests that patients with obsessive-compulsive disorder (OCD)
      have deficits in the volitional control of saccades. Specific evidence comes from
      increased latencies of saccadic eye movements when they were volitionally
      executed but not when they were visually guided. The present study sought to test
      whether this deviance represents a cognitive endophenotype. To this end, first
      degree relatives of OCD patients as genetic risk carriers were compared with OCD
      patients and healthy controls without a family history of OCD. Furthermore, as
      volitional response generation comprises selection and initiation of the required
      response, the study also sought to specify the cognitive mechanisms underlying
      impaired volitional response generation. Twenty-two unaffected first-degree
      relatives of OCD patients, 22 unmedicated OCD patients, and 22 healthy comparison
      subjects performed two types of volitional saccade tasks measuring response
      selection or only response initiation, respectively. Visually guided saccades
      were used as a control condition. Our results showed that unaffected first-degree
      relatives and OCD patients were significantly slowed compared to healthy
      comparison subjects in volitional response selection. Patients and relatives did
      not differ from each other. There was no group difference in the visually guided
      control condition. Taken together, the study provides first evidence that
      dysfunctional volitional response selection is a candidate endophenotype for OCD.

PMID- 22643834
TI  - Development and evaluation of a reverse transcription loop-mediated isothermal
      amplification assay for rapid detection of a new SFTS bunyavirus.
AB  - The etiological agent of severe fever with thrombocytopenia syndrome (SFTS) is a
      bunyavirus that was first identified in China in 2009. We have developed and
      validated a one-step, single-tube, reverse-transcription loop-mediated isothermal
      amplification (RT-LAMP) assay for detection of SFTS bunyavirus (SFTSV). This
      assay demonstrated high specificity and sensitivity, with a detection limit of
      10(1) TCID(50) ml(-1). When combined with the fluorescent detection reagent (FDR)
      method, results could be determined by observing a color change within 30 min. As
      an accurate, rapid, simple and low-cost diagnostic method, this RT-LAMP assay
      will be helpful for detecting and preventing further SFTSV infection in China.

PMID- 22643835
TI  - PINK1 stimulates interleukin-1beta-mediated inflammatory signaling via the
      positive regulation of TRAF6 and TAK1.
AB  - Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic
      neurons in the substantia nigra. The cause of neuronal death in PD is largely
      unknown, but several genetic loci, including PTEN-induced putative kinase 1
      (PINK1), have been linked to early onset autosomal recessive forms of familial
      PD. PINK1 encodes a serine/threonine kinase, which phosphorylates several
      substrates and consequently leads to cell protection against apoptosis induced by
      various stresses. In addition, research has shown that inflammation largely
      contributes to the pathogenesis of PD, but the functional link between PINK1 and
      PD-linked neuroinflammation remains poorly understood. Therefore, in the present
      study, we investigated the functional role of PINK1 in interleukin (IL)-1beta
      mediated inflammatory signaling. We show that PINK1 specifically binds to TRAF6
      and TAK1, and facilitates the autodimerization and autoubiquitination of TRAF6.
      PINK1 also enhances the association between TRAF6 and TAK1, phosphorylates TAK1,
      and stimulates polyubiquitination of TAK1. Furthermore, PINK1 leads to the
      potentiation of IL-1beta-mediated NF-kappaB activity and cytokine production.
      These findings suggest that PINK1 positively regulates two key molecules, TRAF6
      and TAK1, in the IL-1beta-mediated signaling pathway, consequently up-regulating
      their downstream inflammatory events.

PMID- 22643839
TI  - Cytology of five species of subfamily Papaveroideae from the Western Himalayas.
AB  - During the present course, population-based meiotic studies were carried out on
      five species of subfamily Papaveroideae from selected localities of Kashmir and
      Himachal Pradesh in the Western Himalayas (India). Varied intraspecific
      chromosome counts were reported for the first time in Argemone mexicana and
      Meconopsis latifolia, both existing on 2n = 2x = 14. The x = 7, confirmed for the
      first time from the newly found diploid cytotype, is suggested to be the primary
      chromosomal basic number for the Meconopsis. Furthermore, meiotic course was
      noted to be normal in Argemone ochroleuca, it varied from normal to abnormal in
      the populations of A. mexicana and Papaver dubium whereas it was invariably found
      to be abnormal in all the populations of Meconopsis aculeata and M. latifolia.
      These anomalous taxa were marked with meiotic abnormalities in the form of
      cytomixis, chromosomal stickiness, unoriented bivalents, formation of laggards
      and bridges resulting in abnormal microsporogenesis, and production of
      heterogeneous-sized fertile pollen grains along with reduced pollen fertility.

PMID- 22643838
TI  - A novel co-operative mechanism linking TGFbeta and Lyn kinase activation to
      imatinib resistance in chronic myeloid leukaemia cells.
AB  - The advent of a mechanism specific inhibitor imatinib, targeting Bcr-Abl kinase,
      has paved the way for new treatment strategies in chronic myeloid leukaemia
      (CML). However, resistance to imatinib is common in patients and has recently
      been linked to both transforming growth factor-beta (TGFbeta) and elevated Lyn
      kinase activity, although molecular mechanisms remain largely unknown. Here,
      using leukaemic MYL cell lines derived from CML patients, we show that TGFbeta
      plays a key role in imatinib-resistance via direct effects on Lyn ubiquitination
      and turnover that results in bursts of Lyn kinase activity, and identify c-cbl is
      a candidate E3 ubiquitin ligase. Furthermore, blockade of TGFbeta signalling
      activity with the TGFbeta receptor kinase inhibitor SB431542 significantly
      reduces Lyn turnover and activation, and subsequently enhances imatinib-mediated
      CML cell death in a proteasomal-dependent manner. Collectively, our data reveals
      novel co-operative mechanisms in CML involving TGFbeta and Lyn kinase linked to
      proteasome function and ubiquitination, and thus supports therapeutic approaches
      that target TGFbeta pathway activity as a strategy for overcoming imatinib
      resistance in CML.

PMID- 22643836
TI  - Targeting NOX enzymes in the central nervous system: therapeutic opportunities.
AB  - Among the pathogenic mechanisms underlying central nervous system (CNS) diseases,
      oxidative stress is almost invariably described. For this reason, numerous
      attempts have been made to decrease reactive oxygen species (ROS) with the
      administration of antioxidants as potential therapies for CNS disorders. However,
      such treatments have always failed in clinical trials. Targeting specific sources
      of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an
      alternative promising option. Indeed, NOX enzymes are major generators of ROS,
      which regulate progression of CNS disorders as diverse as amyotrophic lateral
      sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On
      the other hand, in autoimmune demyelinating diseases, ROS generated by NOX
      enzymes are protective, presumably by dampening the specific immune response. In
      this review, we discuss the possibility of developing therapeutics targeting
      NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies.
      Specific compounds able to modulate the activation of NOX enzymes, and the
      consequent production of ROS, could fill the need for disease-modifying drugs for
      many incurable CNS pathologies.

PMID- 22643837
TI  - Functional characterization of the human alpha-cardiac actin mutations Y166C and
      M305L involved in hypertrophic cardiomyopathy.
AB  - Inherited cardiomyopathies are caused by point mutations in sarcomeric gene
      products, including alpha-cardiac muscle actin (ACTC1). We examined the
      biochemical and cell biological properties of the alpha-cardiac actin mutations
      Y166C and M305L identified in hypertrophic cardiomyopathy (HCM). Untagged wild
      type (WT) cardiac actin, and the Y166C and M305L mutants were expressed by the
      baculovirus/Sf9-cell system and affinity purified by immobilized gelsolin G4-6.
      Their correct folding was verified by a number of assays. The mutant actins also
      displayed a disturbed intrinsic ATPase activity and an altered polymerization
      behavior in the presence of tropomyosin, gelsolin, and Arp2/3 complex. Both
      mutants stimulated the cardiac beta-myosin ATPase to only 50 % of WT cardiac F
      actin. Copolymers of WT and increasing amounts of the mutant actins led to a
      reduced stimulation of the myosin ATPase. Transfection of established cell lines
      revealed incorporation of EGFP- and hemagglutinin (HA)-tagged WT and both mutant
      actins into cytoplasmic stress fibers. Adenoviral vectors of HA-tagged WT and
      Y166C actin were successfully used to infect adult and neonatal rat
      cardiomyocytes (NRCs). The expressed HA-tagged actins were incorporated into the
      minus-ends of NRC thin filaments, demonstrating the ability to form hybrid thin
      filaments with endogenous actin. In NRCs, the Y166C mutant led after 72 h to a
      shortening of the sarcomere length when compared to NRCs infected with WT actin.
      Thus our data demonstrate that a mutant actin can be integrated into
      cardiomyocyte thin filaments and by its reduced mode of myosin interaction might
      be the basis for the initiation of HCM.

PMID- 22643840
TI  - Genotype-dependent efficiency of endosperm development in culture of selected
      cereals: histological and ultrastructural studies.
AB  - The paper reports studies, including histological and ultrastructural analyses,
      of in vitro cell proliferation and development of immature endosperm tissue
      isolated from caryopses of Triticum aestivum, Triticum durum, and Triticosecale
      plants. Endosperm isolated at 7-10 days post-anthesis developed well on MS medium
      supplemented with auxins and/or cytokinins. The efficiency of endosperm response
      was highly genotype-dependent and best in two winter cultivars of hexaploid
      species. The pathways of development and proliferation were very similar among
      the selected species and cultivars. Histological and scanning electron microscope
      (SEM) analysis revealed that only the part of the endosperm not touching the
      medium surface continued growth and development, resulting in swelling. The
      central part of swollen regions was composed mainly of cells containing many
      large starch grains. The peripheric parts of developed endosperm consisted of
      highly vacuolated cells and small cells with dense cytoplasm. SEM showed that
      cells from the swollen region were covered partially with a membraneous
      structure. Transmission electron microscope studies of cells from the outer part
      of the developing region showed features typical for cell activity connected with
      lipid metabolism.

PMID- 22643841
TI  - Francophone and Anglophone perinatal health: temporal and regional inequalities
      in a Canadian setting, 1981-2008.
AB  - OBJECTIVES: We evaluated temporal and regional inequalities in adverse birth
      outcomes between Anglophones and Francophones of a Canadian province. METHODS:
      Odds ratios and rate differences in preterm birth (PTB, <37 gestational weeks)
      and small-for-gestational-age (SGA) birth were computed for Anglophones relative
      to Francophones for singleton live births in Quebec from 1981 to 2008 (N =
      2,292,237), adjusting for maternal characteristics. Trends over time and
      residential region were evaluated. RESULTS: Rates of PTB and SGA birth overall
      were lower for Anglophones relative to Francophones, but temporal and regional
      trends varied by outcome. Although PTB rates increased over time, inequalities
      between Francophones and Anglophones were relatively stable. In contrast,
      inequalities in SGA birth narrowed over time as Francophone rates declined more
      than Anglophones. Inequalities in SGA birth favored Anglophones overall, but the
      gap gradually reversed in Montreal (the largest metropolitan center) to currently
      favor Francophones. CONCLUSIONS: PTB and SGA birth rates favored Anglophones over
      Francophones. The linguistic gap was generally stable over time for PTB, but
      narrowed or reversed for SGA birth. Language may be used to capture inequalities
      in perinatal health in countries where different linguistic groups predominate.

PMID- 22643842
TI  - Dramatic reduction of sequence artefacts from DNA isolated from formalin-fixed
      cancer biopsies by treatment with uracil- DNA glycosylase.
AB  - Non-reproducible sequence artefacts are frequently detected in DNA from
      formalinfixed and paraffin-embedded (FFPE) tissues. However, no rational strategy
      has been developed for reduction of sequence artefacts from FFPE DNA as the
      underlying causes of the artefacts are poorly understood. As cytosine deamination
      to uracil is a common form of DNA damage in ancient DNA, we set out to examine
      whether treatment of FFPE DNA with uracil-DNA glycosylase (UDG) would lead to the
      reduction of C>T (and G>A) sequence artefacts. Heteroduplex formation in high
      resolution melting (HRM)-based assays was used for the detection of sequence
      variants in FFPE DNA samples. A set of samples that gave false positive HRM
      results for screening for the E17K mutation in exon 4 of the AKT1 gene were
      chosen for analysis. Sequencing of these samples showed multiple non-reproducible
      C:G>T:A artefacts. Treatment of the FFPE DNA with UDG prior to PCR amplification
      led to a very marked reduction of the sequence artefacts as indicated by both HRM
      and sequencing analysis, indicating that uracil lesions are the major cause of
      sequence artefacts. Similar results were shown for the BRAF V600 region in the
      same sample set and EGFR exon 19 in another sample set. UDG treatment
      specifically suppressed the formation of artefacts in FFPE DNA as it did not
      affect the detection of true KRAS codon 12 and true EGFR exon 19 and 20
      mutations. We conclude that uracil in FFPE DNA leads to a significant proportion
      of sequence artefacts. These can be minimised by a simple UDG pretreatment which
      can be readily carried out, in the same tube, as the PCR immediately prior to
      commencing thermal cycling. HRM is a convenient way of monitoring both the degree
      of damage and the effectiveness of the UDG treatment. These findings have
      immediate and important implications for cancer diagnostics where FFPE DNA is
      used as the primary genetic material for mutational studies guiding personalised
      medicine strategies and where simple effective strategies to detect mutations are
      required.

PMID- 22643843
TI  - Paraoxonase 1 and homocysteine metabolism.
AB  - Paraoxonase 1 (PON1), a component of high-density lipoprotein (HDL), is a calcium
      dependent multifunctional enzyme that connects metabolisms of lipoproteins and
      homocysteine (Hcy). Both PON1 and Hcy have been implicated in human diseases,
      including atherosclerosis and neurodegeneration. The involvement of Hcy in
      disease could be mediated through its interactions with PON1. Due to its ability
      to reduce oxidative stress, PON1 contributes to atheroprotective functions of HDL
      in mice and humans. Although PON1 has the ability to hydrolyze a variety of
      substrates, only one of them-Hcy-thiolactone-is known to occur naturally. In
      humans and mice, Hcy-thiolactonase activity of PON1 protects against N
      homocysteinylation, which is detrimental to protein structure and function. PON1
      also protects against neurotoxicity associated with hyperhomocysteinemia in mouse
      models. The links between PON1 and Hcy in relation to pathological states such as
      coronary artery disease, stroke, diabetic mellitus, kidney failure and
      Alzheimer's disease that emerge from recent studies are the topics of this
      review.

PMID- 22643844
TI  - Wards in the keyway: amino acids with anomalous pK(a)s in calycins.
AB  - As a follow-up to our recent analysis of the electrostatics of bovine beta
      lactoglobulin (Eberini et al. in Amino Acids 42:2019-2030, 2011), we investigated
      whether the occurrence in the native structure of calycins-the superfamily to
      which beta-lactoglobulin belongs-of amino acids with anomalous pK (a)s is an
      infrequent or, on the contrary, a common occurrence, and whether or not a general
      pattern may be recognized. To this aim, we randomly selected four calycins we had
      either purified from natural sources or prepared with recombinant DNA
      technologies during our previous and current structural and functional studies on
      this family. Their pIs vary over several pH units and their known functions are
      as diverse as carriers, enzymes, immunomodulators and/or extracellular
      chaperones. In our survey, we used both in silico prediction methods and in vitro
      procedures, such as isoelectric focusing, electrophoretic titration curves and
      spectroscopic techniques. By comparing the results under native conditions (no
      exposure of the proteins to chaotropic agents) to those after protein unfolding
      (in the presence of 8 M urea), a shift is observed in the pK (a) of at least one
      amino acid per protein, which results in a measurable change in pI. Three types
      of amino acids are involved: Cys, Glu, and His, their position varies along the
      calycin sequence. Although no common mechanism may thus be recognized, we
      hypothesize that the 'normalization' of anomalous pK (a)s may be the phenomenon
      that accompanies, and favors, structural rearrangements such as those involved in
      ligand binding by these proteins. An interesting, if anecdotal, validation to
      this view comes from the behavior of human retinol binding protein, for which the
      pI of the folded and liganded protein is intermediate between those of the folded
      and unliganded and of the unfolded protein forms. Likewise, both solid (from
      crystallography) and solution state (from CD spectroscopy) data confirm that the
      protein undergoes structural rearrangement upon retinol binding.

PMID- 22643845
TI  - Regulation of intestinal protein metabolism by amino acids.
AB  - Gut homeostasis plays a major role in health and may be regulated by quantitative
      and qualitative food intake. In the intestinal mucosa, an intense renewal of
      proteins occurs, at approximately 50% per day in humans. In some
      pathophysiological conditions, protein turnover is altered and may contribute to
      intestinal or systemic diseases. Amino acids are key effectors of gut protein
      turnover, both as constituents of proteins and as regulatory molecules limiting
      intestinal injury and maintaining intestinal functions. Many studies have focused
      on two amino acids: glutamine, known as the preferential substrate of rapidly
      dividing cells, and arginine, another conditionally essential amino acid. The
      effects of glutamine and arginine on protein synthesis appear to be model and
      condition dependent, as are the involved signaling pathways. The regulation of
      gut protein degradation by amino acids has been minimally documented until now.
      This review will examine recent data, helping to better understand how amino
      acids regulate intestinal protein metabolism, and will explore perspectives for
      future studies.

PMID- 22643846
TI  - Abundance of amino acid transporters involved in mTORC1 activation in skeletal
      muscle of neonatal pigs is developmentally regulated.
AB  - Previously we demonstrated that the insulin- and amino acid-induced activation of
      the mammalian target of rapamycin complex 1 (mTORC1) is developmentally regulated
      in neonatal pigs. Recent studies have indicated that members of the System A
      transporter (SNAT2), the System N transporter (SNAT3), the System L transporters
      (LAT1 and LAT2), and the proton-assisted amino acid transporters (PAT1 and PAT2)
      have crucial roles in the activation of mTORC1 and that the abundance of amino
      acid transporters is positively correlated with their activation. This study
      aimed to determine the effect of the post-prandial rise in insulin and amino
      acids on the abundance or activation of SNAT2, SNAT3, LAT1, LAT2, PAT1, and PAT2
      and whether the response is modified by development. Overnight fasted 6- and 26
      day-old pigs were infused for 2 h with saline (Control) or with insulin or amino
      acids to achieve fed levels while amino acids or insulin, respectively, as well
      as glucose were maintained at fasting levels. The abundance of SNAT2, SNAT3,
      LAT1, LAT2, PAT1, and PAT2 was higher in muscle of 6- compared with 26-day-old
      pigs. The abundance of the PAT2-mTOR complex was greater in 6- than in 26-day-old
      pigs, consistent with the higher activation of mTORC1. Neither insulin nor amino
      acids altered amino acid transporter or PAT2-mTOR complex abundance. In
      conclusion, the amino acid transporters, SNAT 2/3, LAT 1/2, and PAT1/2, likely
      have important roles in the enhanced amino acid-induced activation of mTORC1 in
      skeletal muscle of the neonate.

PMID- 22643847
TI  - Solid tumor differentiation therapy - is it possible?
AB  - Genetic and epigenetic events within a cell which promote a block in normal
      development or differentiation coupled with unregulated proliferation are
      hallmarks of neoplastic transformation. Differentiation therapy involves the use
      of agents with the ability to induce differentiation in cells that have lost this
      ability, i.e. cancer cells. The promise of differentiation-based therapy as a
      viable treatment modality is perhaps best characterized by the addition of
      retinoids in the treatment of acute promyelocytic leukemia (APML) revolutionizing
      the management of APML and dramatically improving survival. However, interest and
      application of differentiationbased therapy for the treatment of solid
      malignancies have lagged due to deficiencies in our understanding of
      differentiation pathways in solid malignancies. Over the past decade, a
      differentiation-based developmental model for solid tumors has emerged providing
      insights into the biology of various solid tumors as well as identification of
      targetable pathways capable of re-activating blocked terminal differentiation
      programs. Furthermore, a variety of agents including retinoids, histone
      deacetylase inhibitors (HDACI), PPARgamma agonists, and others, currently in use
      for a variety of malignancies, have been shown to induce differentiation in solid
      tumors. Herein we discuss the relevancy of differentiation-based therapies in
      solid tumors, using soft tissue sarcomas (STS) as a biologic and clinical model,
      and review the preclinical data to support its role as a promising modality of
      therapy for the treatment of solid tumors.

PMID- 22643848
TI  - Major depressive disorder in the perinatal period: using data linkage to inform
      perinatal mental health policy.
AB  - This study aims to investigate hospital admission of major depressive disorders
      (MDD) before and after birth. Population data for all primiparous women admitted
      to the hospital with depressive disorders before and after birth were used. The
      comparison group consisted of 10 % of primiparous women not admitted to the
      hospital with a diagnosis of a psychiatric disorder or substance use. A total of
      728 women had a first admission with depressive disorders (501 in the first
      postpartum year). The rate of first hospital admission for depressive disorders
      decreased during pregnancy and increased markedly in the first three months after
      birth (peaking in the second month with a rate of 10.74/1,000 person year and
      rate ratio of 12.56) compared with the 6 months prior to pregnancy. Admission
      remained elevated in the second postpartum year. Older maternal age, smoking,
      elective caesarian section and admission to a neonatal intensive care unit or
      special care nursery were associated with a higher rate of admission. Women born
      outside Australia and those most socioeconomically disadvantaged were less likely
      to be admitted to the hospital in the first postpartum year. Overall risk of
      hospital admission with depressive disorders rose significantly across the entire
      first postpartum year. This has significant implications for policy and service
      planning for women with mood disorders in the perinatal period.

PMID- 22643861
TI  - Proofreading of misincorporated nucleotides in DNA transcription.
AB  - The accuracy of DNA transcription is crucial for the proper functioning of the
      cell. Although RNA polymerases demonstrate selectivity for correct nucleotides,
      additional active mechanisms of transcriptional error correction are required to
      achieve observed levels of fidelity. Recent experimental findings have shed light
      on a particular mechanism of transcriptional error correction involving: (i)
      diffusive translocation of the RNA polymerase along the DNA (backtracking) and
      (ii) irreversible RNA cleavage. This mechanism achieves preferential cleavage of
      misincorporated nucleotides by biasing the local rates of translocation. Here, we
      study how misincorporated nucleotides affect backtracking dynamics and how this
      effect determines the level of transcriptional fidelity. We consider backtracking
      as a diffusive process in a periodic, one-dimensional energy landscape, which at
      a coarse-grained level gives rise to a hopping process between neighboring local
      minima. We propose a model for how misincorporated nucleotides deform this energy
      landscape and hence affect the hopping rates. In particular, we show that this
      model can be used to derive both the theoretical limit on the fidelity (i.e. the
      minimum fraction of misincorporated nucleotides) and the actual fidelity relative
      to this optimum, achieved for specific combinations of the cleavage and
      polymerization rates. Finally, we study how external factors influencing
      backtracking dynamics affect transcriptional fidelity. We show that biologically
      relevant loads, similar to those exerted by nucleosomes or other transcriptional
      barriers, increase error correction.

PMID- 22643849
TI  - Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with
      mucosal damage in SIV infection.
AB  - Human immunodeficiency virus (HIV) and Simian immunodeficiency virus (SIV)
      disease progression is associated with multifocal damage to the gastrointestinal
      tract epithelial barrier that correlates with microbial translocation and
      persistent pathological immune activation, but the underlying mechanisms remain
      unclear. Investigating alterations in mucosal immunity during SIV infection, we
      found that damage to the colonic epithelial barrier was associated with loss of
      multiple lineages of interleukin (IL)-17-producing lymphocytes, cells that
      microarray analysis showed expressed genes important for enterocyte homeostasis,
      including IL-22. IL-22-producing lymphocytes were also lost after SIV infection.
      Potentially explaining coordinate loss of these distinct populations, we also
      observed loss of CD103+ dendritic cells (DCs) after SIV infection, which
      associated with the loss of IL-17- and IL-22-producing lymphocytes. CD103+ DCs
      expressed genes associated with promotion of IL-17/IL-22+ cells, and coculture of
      CD103+ DCs and naive T cells led to increased IL17A and RORc expression in
      differentiating T cells. These results reveal complex interactions between
      mucosal immune cell subsets providing potential mechanistic insights into
      mechanisms of mucosal immune dysregulation during HIV/SIV infection, and offer
      hints for development of novel therapeutic strategies to address this aspect of
      AIDS virus pathogenesis.

PMID- 22643862
TI  - The naturally occurring aliphatic isothiocyanates sulforaphane and erucin are
      weak agonists but potent non-competitive antagonists of the aryl hydrocarbon
      receptor.
AB  - As the Ah receptor target gene products play a critical role in chemical
      carcinogenesis, antagonists are considered as potential chemopreventive agents.
      It is demonstrated in this paper that the isothiocyanates R,S-sulforaphane and
      erucin are non-competitive antagonists of the aryl hydrocarbon (Ah) receptor.
      Both isothiocyanates were poor agonists for the receptor and elevated CYP1A1 mRNA
      levels only modestly when incubated with precision-cut rat liver slices. In
      contrast, the classical Ah receptor agonist benzo[a]pyrene was a potent inducer
      of CYP1A1 mRNA levels, with this effect being effectively antagonized by the two
      isothiocyanates. In further studies, it was demonstrated that R,S-sulforaphane
      could both prevent the interaction of and displace already bound benzo[a]pyrene
      from the Ah receptor, but no concentration dependency was observed with respect
      to the isothiocyanate. Both erucin and R,S-sulforaphane antagonized the
      benzo[a]pyrene-mediated increase in the CYP1A-mediated O-deethylation of
      ethoxyresorufin in rat precision-cut liver slices. Of the two isomers of R,S
      sulforaphane, the naturally occurring R-isomer was more effective than the S
      isomer in antagonizing the activation of the Ah receptor by benzo[a]pyrene.
      Antagonism of the Ah receptor may be a major contributor to the established
      chemoprevention of aliphatic isothiocyanates.

PMID- 22643863
TI  - Time to onset of efficacy in fracture reduction with current anti-osteoporosis
      treatments.
AB  - Early prevention of future fracture is an important goal in those at risk. A
      similar 3-year fracture efficacy is reported for most osteoporosis agents. Onset
      of fracture efficacy may be useful to help tailor treatment based on risk. We
      reviewed the peer-reviewed literature for onset of fracture efficacy data on the
      commonly prescribed osteoporosis treatments. All papers were reviewed
      independently by at least two reviewers for onset of efficacy for morphometric
      vertebral fracture (MVF), clinical vertebral fracture (CVF), nonvertebral
      fracture (NVF), hip fracture, and any clinical fracture (ACF). Alendronate is
      reported to reduce multiple CVF by 6 months; all CVF, NVF, and multiple ACF by 12
      months; and all ACF and hip fracture by 18 months. Ibandronate is reported to
      reduce MVF by 12 months and NVF by 36 months. Raloxifene is reported to reduce
      CVF by 3-6 months and NVF by 36 months. Risedronate is reported to reduce CVF and
      NVF by 6 months, and hip fracture by 12 months. Strontium ranelate is reported to
      reduce MVF, CVF, NVF, and ACF by 12 months, and hip fracture by 36 months.
      Zoledronic acid is reported to reduce MVF, CVF, and ACF by 12 months, NVF by 24
      months, and hip fracture by 36 months. Although direct comparisons are limited,
      based on the available literature, risedronate, followed by alendronate, have the
      earliest onset of benefit across the range of fracture types. Onset of efficacy
      may be an important consideration in the selection of treatment for some
      patients.

PMID- 22643864
TI  - Targeting the hemoglobin scavenger receptor CD163 in macrophages highly increases
      the anti-inflammatory potency of dexamethasone.
AB  - Synthetic glucocorticoids are potent anti-inflammatory drugs but serious side
      effects such as bone mobilization, muscle mass loss, immunosuppression, and
      metabolic alterations make glucocorticoid therapy a difficult balance. The
      therapeutic anti-inflammatory effect of glucocorticoids relies largely on the
      suppressed release of tumor-necrosis factor-alpha and other cytokines by
      macrophages at the sites of inflammation. We have now developed a new
      biodegradable anti-CD163 antibody-drug conjugate that specifically targets the
      glucocorticoid, dexamethasone to the hemoglobin scavenger receptor CD163 in
      macrophages. The conjugate, that in average contains four dexamethasone molecules
      per antibody, exhibits retained high functional affinity for CD163. In vitro
      studies in rat macrophages and in vivo studies of Lewis rats showed a strong anti
      inflammatory effect of the conjugate measured as reduced lipopolysaccharide
      induced secretion of tumor-necrosis factor-alpha. The in vivo potency of
      conjugated dexamethasone was about 50-fold that of nonconjugated dexamethasone.
      In contrast to a strong systemic effect of nonconjugated dexamethasone, the
      equipotent dose of the conjugate had no such effect, measured as thymus
      lymphocytes apoptosis, body weight loss, and suppression of endogenous cortisol
      levels. In conclusion, the study shows antibody-drug conjugates as a future
      approach in anti-inflammatory macrophage-directed therapy. Furthermore, the data
      demonstrate CD163 as an excellent macrophage target for anti-inflammatory drug
      delivery.

PMID- 22643865
TI  - MyD88 signaling in B cells regulates the production of Th1-dependent antibodies
      to AAV.
AB  - The administration of recombinant adeno-associated viral vectors (rAAV) for gene
      transfer induces strong humoral responses through mechanisms that remain
      incompletely characterized. To investigate the links between innate and adaptive
      immune responses to the vector, rAAVs were injected intravenously into mice
      deficient in cell-intrinsic components of innate responses (Toll-like receptors
      (TLRs), type-1 interferon (IFN) or inflammasome signaling molecules) and AAV
      specific antibodies were measured. Of all molecules tested, only MyD88 was
      critically needed to mount immunoglobulin G (IgG) responses since MyD88(-/-) mice
      failed to develop high levels of AAV-specific IgG2 and IgG3, regardless of capsid
      serotype injected. None of the TLRs tested was essential here, but TLR9 ensured a
      Th1-biased antibody responses. Indeed, capsid-specific Th1 cells were induced
      upon injection of rAAV1, as directly confirmed with an epitope-tagged capsid, and
      the priming and development of these Th1 cells required T cell-extrinsic MyD88.
      Cell transfer experiments showed that autonomous MyD88 signaling in B cells, but
      not T cells, was sufficient to produce Th1-dependent IgGs. Therefore, rAAV
      triggers innate responses, at least via B cells, controlling the development of
      capsid-specific Th1-driven antibodies. MyD88 emerges as a critical and pivotal
      regulator of both T- and B-cell adaptive immunity against AAV.

PMID- 22643866
TI  - A cell-penetrating helical polymer for siRNA delivery to mammalian cells.
AB  - Cell-penetrating peptides (CPPs) are routinely used for intracellular delivery of
      a variety of cargo, including drugs, genes, and short interfering RNA (siRNA).
      Most CPPs are active only upon exposure to acidic environments inside of late
      endosomes, thereby facilitating the endosomal escape of internalized vectors.
      Here, we describe the generation of a synthetic polypeptide--PVBLG(n)-8--that is
      able to adopt a helical structure independent of pH. Like other CPPs, the helical
      structure of PVBLG(n)-8 allows the polypeptide to destabilize membranes. However,
      since the helix is stable at all physiologically relevant pH values between pH 2
      and pH 7.4, the membrane permeation properties of PVBLG(n)-8 are irreversible.
      Given its pH-insensitive activity, our results suggest that PVBLG(n)-8 is able to
      facilitate efficient siRNA delivery by causing pore formation in the cell
      membranes through which either free or complexed siRNA is able to diffuse. This
      nonspecific form of entry into the cell cytosol may prove useful when trying to
      deliver siRNA to cells which have proven to be difficult to transfect.

PMID- 22643867
TI  - Mindin your own business.

PMID- 22643869
TI  - Decoherence effects on superpositions of chiral states in a chiral molecule.
AB  - The superposition of chiral states of chiral molecules, as delocalized quantum
      states of a many-particle system, can be used for the experimental investigations
      of decoherence theory. In this regard, a great challenge is the precise
      quantification of the robustness of these superpositions against environmental
      effects. The methods so far proposed need the detailed specification of the
      internal states of the molecule, usually requiring heavy numerical calculations.
      Here, by using the linearized quantum Boltzmann equation and by borrowing ideas
      employed for analyzing other quantum systems, we present a general and simple
      approach, of wide applicability, which can be used to compute the dominant
      contribution to the decoherence rate for the superpositions of chiral states of
      chiral molecules, due to environmental scattering.

PMID- 22643868
TI  - Human induced pluripotent stem cells--from mechanisms to clinical applications.
AB  - Human pluripotent stem cells hold great promise for basic research and
      regenerative medicine due to their inherent property to propagate infinitely,
      while maintaining the potential to differentiate into any given cell type of the
      human body. Since the first derivation in 1998, pluripotent human embryonic stem
      cells (ESCs) have been studied intensively, and although these cells provoke
      ethical and immune rejection concerns, translation of human ESC research into the
      clinics has been initiated. The generation of embryonic stem cell-like human
      induced pluripotent stem cells (iPSCs) from somatic cells by virus-mediated
      overexpression of distinct sets of reprogramming factors (OCT4, SOX2, KLF4, and c
      MYC, or OCT4, SOX2, NANOG, and LIN28) in 2007 has opened up further opportunities
      in the field. While circumventing the major disputes associated with human ESCs,
      iPSCs offer the same advantages and, in addition, new perspectives for
      personalized medicine. This review summarizes technical advances toward the
      generation of potentially clinically relevant human iPSCs. We also highlight key
      molecular events underlying the process of cellular reprogramming and discuss
      inherent features of iPSCs, including genome instability and epigenetic memory.
      Furthermore, we will give an overview of particular envisaged human iPSC
      applications and point out which improvements are yet to come and what has been
      achieved so far.

PMID- 22643870
TI  - Rapid determination of the thermal nociceptive threshold in diabetic rats.
AB  - Painful diabetic neuropathy (PDN) is characterized by hyperalgesia i.e.,
      increased sensitivity to noxious stimulus, and allodynia i.e., hypersensitivity
      to normally innocuous stimuli. Hyperalgesia and allodynia have been studied in
      many different rodent models of diabetes mellitus. However, as stated by Bolcskei
      et al, determination of "pain" in animal models is challenging due to its
      subjective nature. Moreover, the traditional methods used to determine behavioral
      responses to noxious thermal stimuli usually lack reproducibility and
      pharmacological sensitivity. For instance, by using the hot-plate method of
      Ankier, flinch, withdrawal and/or licking of either hind- and/or fore-paws is
      quantified as reflex latencies at constant high thermal stimuli (52-55  degrees
      C). However, animals that are hyperalgesic to thermal stimulus do not
      reproducibly show differences in reflex latencies using those supra-threshold
      temperatures. As the recently described method of Bolcskei et al., the procedures
      described here allows for the rapid, sensitive and reproducible determination of
      thermal nociceptive thresholds (TNTs) in mice and rats. The method uses slowly
      increasing thermal stimulus applied mostly to the skin of mouse/rat plantar
      surface. The method is particularly sensitive to study anti-nociception during
      hyperalgesic states such as PDN. The procedures described bellow are based on the
      ones published in detail by Almasi et al and Bolcskei et al. The procedures
      described here have been approved the Laboratory Animal Care and Use Committee
      (LACUC), Wright State University.

PMID- 22643872
TI  - Stem cell research: Regulating translational application.

PMID- 22643871
TI  - Postoperative failure of platelet recovery is an independent risk factor for poor
      survival in patients with oral and oropharyngeal cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the postoperative platelet count
      changes in patients with oral and oropharyngeal squamous cell carcinoma
      undergoing preoperative chemoradiotherapy in order to test the hypothesis that
      the failure of platelets to recover to normal range within 7 days after surgery
      represents a significant risk factor for poor survival. MATERIALS AND METHODS: A
      cohort of 102 patients with primary locally advanced oral and oropharyngeal
      squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy and surgery was
      retrospectively analyzed. For each patient, platelet counts were evaluated prior
      to neoadjuvant treatment, prior to surgery and throughout postoperative days 1 to
      7. The Kaplan-Meier method and Cox regression models were used to assess the
      impact of platelet count changes on survival. RESULTS: Overall survival rate at 5
      years was 28% for patients whose platelets did not recover by day 7, with 52% for
      patients whose platelets remained within a normal level or recovered to this by
      day 7 (p = 0.005). In multivariate analysis, failure of platelet recovery by day
      7 was independently associated with shorter overall survival (p = 0.03).
      CONCLUSIONS: We demonstrated that the failure of platelets to recover to normal
      range by the seventh postoperative day is an independent adverse prognostic
      factor in patients with oral and oropharyngeal cancer undergoing neoadjuvant
      treatment and surgery. CLINICAL RELEVANCE: Our results indicate that physicians
      should pay closer attention to monitoring the postoperative platelet count
      course, as it may predict the clinical outcome of patients with oral and
      oropharyngeal cancer.

PMID- 22643873
TI  - Redefining differentiation: Reshaping our ends.

PMID- 22643874
TI  - Cdt1 throws kinetochore-microtubule attachments for a loop.
AB  - The Ndc80 complex links spindle microtubules to the kinetochore to ensure the
      proper segregation of chromosomes during mitosis. Analysis of the replication
      licensing factor Cdt1 during mitosis now reveals a cooperative role with the
      Ndc80 complex in establishing stable microtubule attachments to the spindle.

PMID- 22643875
TI  - Mcl-1 rescues a glitch in the matrix.
AB  - Bcl-2 family proteins are known to control cell death and influence mitochondrial
      function. The function of Mcl-1, an anti-apoptotic Bcl-2 protein, is now shown to
      depend on its subcellular localization. Mcl-1 at the mitochondrial outer membrane
      inhibits mitochondrial permeabilization to block apoptosis. However, a cleaved
      form of Mcl-1 localizes to the mitochondrial matrix and controls inner
      mitochondrial morphology and oxidative phosphorylation, without directly
      modulating apoptosis.

PMID- 22643882
TI  - An equal sex ratio followed by differential sex mortality causes overestimation
      of females in gall midges: no evidence for sex ratio regulation.
AB  - Monogeny, the production of unisexual broods by individual females, has been
      recognized for nearly 80 years. The genetic nature of gall midges' sex
      determination predicts an equal numbers of male-producing and female-producing
      females in the populations such that the overall sex ratio is expected to be
      nearly 1:1. However, observations of some strictly monogenous populations with
      biased sex ratio, mainly toward females, have raised the question of whether gall
      midges are able to adjust their offspring sex ratio in response to changes in
      environmental conditions, and some authors have even considered sex ratio
      regulation as a strong force in the course of the evolution of monogeny. In this
      paper, first, by studying the sex ratio variations of the predatory gall midge,
      Aphidoletes aphidimyza within a generation, we showed that adult males emerge up
      to 1 day earlier and have shorter life span than females (less than 4 days and up
      to 6 days, respectively). Although, the sex ratio of A. aphidimyza at the time of
      emergence was nearly 1:1 (52.41% males), a simple population simulation indicated
      that the differential mortality of sexes can lead to a female-biased sex ratio
      estimation (57.88% females) under random sampling in the natural environments.
      Our results imply that the primary sex ratio of monogenous gall midges is nearly
      1:1 and that the arrhenogenic/thelygenic gall midges are not able to alter the
      number of their male/female progenies in response to changes in environmental
      conditions.

PMID- 22643883
TI  - Facile synthesis and optical properties of magic-number Au13 clusters.
AB  - Synthesis of molecular gold clusters through a post-synthetic scheme involving
      HCl-promoted nuclearity convergence was examined with various phosphine ligands.
      Systematic studies with a series of bis(diphenylphosphino) ligands (Ph(2)P
      (CH(2))(m)-PPh(2)) using electrospray ionization mass spectrometry (ESI-MS) and
      electronic absorption spectroscopy demonstrated that the use of dppp (m = 3),
      dppb (m = 4) and dpppe (m = 5) as the ligands resulted in the formation of
      [Au(13)P(8)Cl(4)](+) type clusters, whereas the [Au(13)P(10)Cl(2)](3+) type
      cluster was formed with dppe (m = 2). The cluster species did not survive the HCl
      treatment step when monophosphines PPh(3), PMe(2)Ph, and POct(3) were employed,
      but [Au(13)(POct(3))(8)Cl(4)](+) was isolated as a minor product in the NaBH(4)
      reduction of Au(POct(3))Cl in aqueous THF. Electronic absorption and
      photoluminescence studies of a series of Au(13) clusters revealed that their
      optical properties are highly dependent on the phosphine/chloride composition
      ratio, but are far less so on the phosphine structure.

PMID- 22643884
TI  - Local and global methods of assessing thermal nociception in Drosophila larvae.
AB  - In this article, we demonstrate assays to study thermal nociception in Drosophila
      larvae. One assay involves spatially-restricted (local) stimulation of thermal
      nociceptors while the second involves a wholesale (global) activation of most or
      all such neurons. Together, these techniques allow visualization and
      quantification of the behavioral functions of Drosophila nociceptive sensory
      neurons. The Drosophila larva is an established model system to study thermal
      nociception, a sensory response to potentially harmful temperatures that is
      evolutionarily conserved across species. The advantages of Drosophila for such
      studies are the relative simplicity of its nervous system and the sophistication
      of the genetic techniques that can be used to dissect the molecular basis of the
      underlying biology In Drosophila, as in all metazoans, the response to noxious
      thermal stimuli generally involves a "nocifensive" aversive withdrawal to the
      presented stimulus. Such stimuli are detected through free nerve endings or
      nociceptors and the amplitude of the organismal response depends on the number of
      nociceptors receiving the noxious stimulus. In Drosophila, it is the class IV
      dendritic arborization sensory neurons that detect noxious thermal and mechanical
      stimuli in addition to their recently discovered role as photoreceptors. These
      neurons, which have been very well studied at the developmental level, arborize
      over the barrier epidermal sheet and make contacts with nearly all epidermal
      cells. The single axon of each class IV neuron projects into the ventral nerve
      cord of the central nervous system where they may connect to second-order neurons
      that project to the brain. Under baseline conditions, nociceptive sensory neurons
      will not fire until a relatively high threshold is reached. The assays described
      here allow the investigator to quantify baseline behavioral responses or,
      presumably, the sensitization that ensues following tissue damage. Each assay
      provokes distinct but related locomotory behavioral responses to noxious thermal
      stimuli and permits the researcher to visualize and quantify various aspects of
      thermal nociception in Drosophila larvae. The assays can be applied to larvae of
      desired genotypes or to larvae raised under different environmental conditions
      that might impact nociception. Since thermal nociception is conserved across
      species, the findings gleaned from genetic dissection in Drosophila will likely
      inform our understanding of thermal nociception in other species, including
      vertebrates.

PMID- 22643885
TI  - Traits of ADHD and autism in girls with a twin brother: a Mendelian randomization
      study.
AB  - It has been hypothesized that prenatal exposure to testosterone may be associated
      with traits of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum
      disorder (ASD). We conducted a population-based study of dizygotic female twins
      to elucidate this hypothesis, assuming that the sex of the co-twin influences the
      level of prenatal exposure to testosterone. We invited parents of 24,552 3- to 15
      year-old twins to answer questionnaires on traits of ADHD and ASD. We analysed
      the data using a proportional odds model with sex of the co-twin as an
      instrumental variable for prenatal exposure to testosterone of female twins. We
      received responses for 6,339 girls from dizygotic twin pairs. Odds ratios for
      male versus female co-twin were 0.71 (95 % confidence interval 0.61-0.81) for
      ADHD traits and 0.74 (0.66-0.83) for ASD traits, indicating that a twin brother
      reduces traits of ADHD and ASD in females. In conclusion, we found that female
      twins with a twin brother scored significantly lower in parent-reported traits of
      ADHD and ASD than those with a twin sister. The reason for this may be parental
      reporting bias, or confounding by unmeasured variables, or a causal effect of an
      intrauterine environment modified by the sex of the co-twin in the opposite
      direction of what we expected.

PMID- 22643887
TI  - Orbital switching in a frustrated magnet.
AB  - The orbital is one of the four fundamental degrees of freedom in a solid, besides
      spin, charge and lattice. In transition metal compounds, it is usually the d
      orbitals which play deciding roles in determining the crystallographic and
      physical properties. Here we report the discovery of a unique structural
      transition in single crystals of the spin-1/2 quasi-kagome antiferromagnet
      volborthite, Cu(3)V(2)O(7)(OH)(2).2H(2)O, whereby the unpaired electron
      'switches' from one d orbital to another upon cooling. This is not a conventional
      orbital order-disorder transition, but rather an orbital switching that has not
      previously been observed. The structural transition is found to profoundly affect
      the magnetic properties of volborthite, because magnetic interactions between Cu
      spins in the kagome lattice are considerably modified by the orbital switching.
      This finding provides us with an interesting example to illustrate the intimate
      interplay between the orbital degree of freedom and competing magnetic
      interactions in a frustrated magnet.

PMID- 22643886
TI  - The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac
      pathway and cell motility.
AB  - Dishevelled is the common mediator of canonical and non-canonical Wnt signalling
      pathways, which are important for embryonic development, tissue maintenance and
      cancer progression. In the non-canonical Wnt signalling pathway, the Rho family
      of small GTPases acting downstream of Dishevelled has essential roles in cell
      migration. The mechanisms by which the non-canonical Wnt signalling pathway
      regulates Rac activation remain unknown. Here we show that Daple (Dishevelled
      associating protein with a high frequency of leucine residues) regulates Wnt5a
      mediated activation of Rac and formation of lamellipodia through interaction with
      Dishevelled. Daple increases the association of Dishevelled with an isoform of
      atypical protein kinase C, consequently promoting Rac activation. Accordingly,
      Daple deficiency impairs migration of fibroblasts and epithelial cells during
      wound healing in vivo. These findings indicate that Daple interacts with
      Dishevelled to direct the Dishevelled/protein kinase lambda protein complex to
      activate Rac, which in turn mediates the non-canonical Wnt signalling pathway
      required for cell migration.

PMID- 22643888
TI  - Assembly kinetics determine the architecture of alpha-actinin crosslinked F-actin
      networks.
AB  - The actin cytoskeleton is organized into diverse meshworks and bundles that
      support many aspects of cell physiology. Understanding the self-assembly of these
      actin-based structures is essential for developing predictive models of
      cytoskeletal organization. Here we show that the competing kinetics of bundle
      formation with the onset of dynamic arrest arising from filament entanglements
      and crosslinking determine the architecture of reconstituted actin networks
      formed with alpha-actinin crosslinks. Crosslink-mediated bundle formation only
      occurs in dilute solutions of highly mobile actin filaments. As actin
      polymerization proceeds, filament mobility and bundle formation are arrested
      concomitantly. By controlling the onset of dynamic arrest, perturbations to actin
      assembly kinetics dramatically alter the architecture of biochemically identical
      samples. Thus, the morphology of reconstituted F-actin networks is a kinetically
      determined structure similar to those formed by physical gels and glasses. These
      results establish mechanisms controlling the structure and mechanics in diverse
      semiflexible biopolymer networks.

PMID- 22643889
TI  - The oceanic biological pump modulates the atmospheric transport of persistent
      organic pollutants to the Arctic.
AB  - Semivolatile persistent organic pollutants have the potential to reach remote
      environments, such as the Arctic Ocean, through atmospheric transport and
      deposition. Here we show that this transport of polychlorinated biphenyls to the
      Arctic Ocean is strongly retarded by the oceanic biological pump. A simultaneous
      sampling of atmospheric, seawater and plankton samples was performed in July 2007
      in the Greenland Current and Atlantic sector of the Arctic Ocean. The atmospheric
      concentrations declined during atmospheric transport over the Greenland Current
      with estimated half-lives of 1-4 days. These short half-lives can be explained by
      the high air-to-water net diffusive flux, which is similar in magnitude to the
      estimated settling fluxes in the water column. Therefore, the decrease of
      atmospheric concentrations is due to sequestration of atmospheric polychlorinated
      biphenyls by enhanced air-water diffusive fluxes driven by phytoplankton uptake
      and organic carbon settling fluxes (biological pump).

PMID- 22643890
TI  - Inbreeding causes early death in a passerine bird.
AB  - Inbreeding typically reduces fitness. Related partners may fail to reproduce and
      any inbred offspring may die early or fail to reproduce themselves. Here we show
      that inbreeding causes early death in the zebra finch Taeniopygia guttata, and
      among inbred individuals of the same inbreeding coefficient (F), those that die
      early are more homozygous (estimated from single nucleotide polymorphisms) than
      those that survive to adulthood. Therefore, we identify two ways by which
      inbreeding depression may be underestimated in studies of inbreeding. First, a
      failure to study early life history could mean that the magnitude of inbreeding
      depression is routinely underestimated. Second, the observation that the most
      homozygous individuals of the same pedigree F were the least likely to survive to
      sexual maturity provides evidence that realized inbreeding, estimated from a high
      density of markers spread throughout the genome, explains variation in survival
      above and beyond what pedigree-based measures of inbreeding can explain.

PMID- 22643891
TI  - Robust classification of salient links in complex networks.
AB  - Complex networks in natural, social and technological systems generically exhibit
      an abundance of rich information. Extracting meaningful structural features from
      data is one of the most challenging tasks in network theory. Many methods and
      concepts have been proposed to address this problem such as centrality
      statistics, motifs, community clusters and backbones, but such schemes typically
      rely on external and arbitrary parameters. It is unknown whether generic networks
      permit the classification of elements without external intervention. Here we show
      that link salience is a robust approach to classifying network elements based on
      a consensus estimate of all nodes. A wide range of empirical networks exhibit a
      natural, network-implicit classification of links into qualitatively distinct
      groups, and the salient skeletons have generic statistical properties. Salience
      also predicts essential features of contagion phenomena on networks, and points
      towards a better understanding of universal features in empirical networks that
      are masked by their complexity.

PMID- 22643892
TI  - Metformin elicits anticancer effects through the sequential modulation of DICER
      and c-MYC.
AB  - Diabetic patients treated with metformin have a reduced incidence of cancer and
      cancer-related mortality. Here we show that metformin affects engraftment and
      growth of breast cancer tumours in mice. This correlates with the induction of
      metabolic changes compatible with clear anticancer effects. We demonstrate that
      microRNA modulation underlies the anticancer metabolic actions of metformin. In
      fact, metformin induces DICER expression and its effects are severely impaired in
      DICER knocked down cells. Conversely, ectopic expression of DICER recapitulates
      the effects of metformin in vivo and in vitro. The microRNAs upregulated by
      metformin belong mainly to energy metabolism pathways. Among the messenger RNAs
      downregulated by metformin, we found c-MYC, IRS-2 and HIF1alpha. Downregulation
      of c-MYC requires AMP-activated protein kinase-signalling and mir33a upregulation
      by metformin. Ectopic expression of c-MYC attenuates the anticancer metabolic
      effects of metformin. We suggest that DICER modulation, mir33a upregulation and c
      MYC targeting have an important role in the anticancer metabolic effects of
      metformin.

PMID- 22643893
TI  - Dynamic force-induced direct dissociation of protein complexes in a nuclear body
      in living cells.
AB  - Despite past progress in understanding mechanisms of cellular
      mechanotransduction, it is unclear whether a local surface force can directly
      alter nuclear functions without intermediate biochemical cascades. Here we show
      that a local dynamic force via integrins results in direct displacements of
      coilin and SMN proteins in Cajal bodies and direct dissociation of coilin-SMN
      associated complexes. Spontaneous movements of coilin increase more than those of
      SMN in the same Cajal body after dynamic force application. Fluorescence
      resonance energy transfer changes of coilin-SMN depend on force magnitude, an
      intact F-actin, cytoskeletal tension, Lamin A/C, or substrate rigidity. Other
      protein pairs in Cajal bodies exhibit different magnitudes of fluorescence
      resonance energy transfer. Dynamic cyclic force induces tiny phase lags between
      various protein pairs in Cajal bodies, suggesting viscoelastic interactions
      between them. These findings demonstrate that dynamic force-induced direct
      structural changes of protein complexes in Cajal bodies may represent a unique
      mechanism of mechanotransduction that impacts on nuclear functions involved in
      gene expression.

PMID- 22643894
TI  - Ultra-low-loss optical delay line on a silicon chip.
AB  - Light propagation through an optical fibre causes a long, non-resonant (true)
      time delay used in numerous applications. In contrast to how it is deployed in
      optical communication systems, fibre is coiled in these applications to reduce
      footprint. This is a configuration better suited for a chip-based waveguide that
      would improve shock resistance, and afford the possibility of integration for
      system-on-a-chip functionality. However, integrated waveguide attenuation rates
      lag far behind the corresponding rates of optical fibre, featuring attenuation
      many orders larger. Here we demonstrate a monolithic waveguide as long as 27 m
      (39 m optical path length), and featuring broadband loss rate values of (0.08+/
      0.01) dB m(-1) measured over 7 m by optical backscatter. Resonator measurements
      show a further reduction of loss to 0.037 dB m(-1), close to that of optical
      fibres when first considered a viable technology. Scaling this waveguide to
      integrated spans exceeding 250 m and attenuation rates below 0.01 dB m(-1) is
      discussed.

PMID- 22643895
TI  - Prediction of variable translation rate effects on cotranslational protein
      folding.
AB  - The concomitant folding of a protein with its synthesis on the ribosome is
      influenced by a number of different timescales including the translation rate.
      Here we present a kinetic formalism to describe cotranslational folding and
      predict the effects of variable translation rates on this process. Our approach,
      which utilizes equilibrium data from arrested ribosome nascent chain complexes,
      provides domain folding probabilities in quantitative agreement with molecular
      simulations of folding at different translation rates. We show that the effects
      of single codon mutations in messenger RNA that alter the translation rate can
      lead to a dramatic increase in the extent of folding under specific conditions.
      The kinetic formalism that we discuss can describe the cotranslational folding
      process occurring on a single ribosome molecule as well as for a collection of
      stochastically translating ribosomes.

PMID- 22643896
TI  - O-glycosylation modulates integrin and FGF signalling by influencing the
      secretion of basement membrane components.
AB  - Extracellular microenvironments have crucial roles in modulating cell
      interactions during development. Here we discover that a conserved protein
      modification (O-glycosylation) influences extracellular matrix composition during
      mammalian organogenesis, affecting integrin signalling and fibroblast growth
      factor-mediated cell proliferation. Specifically, mice deficient for an enzyme
      (Galnt1) that adds sugars to proteins during early stages of organogenesis
      resulted in intracellular accumulation of major basement membrane proteins and
      endoplasmic reticulum stress, with resultant effects on fibroblast growth factor
      signalling, epithelial cell proliferation and organ growth. Exogenous addition of
      basement membrane components rescued fibroblast growth factor signalling and the
      growth defects in a beta1-integrin-dependent manner. Our work demonstrates for
      the first time that O-glycosylation influences the composition of the
      extracellular matrix during mammalian organ development, influencing specific
      aspects of the endoplasmic reticulum stress response, cell signalling, cell
      proliferation and organ growth. Our work provides insight into the role of this
      conserved protein modification in both development and disease.

PMID- 22643897
TI  - Twisted optical metamaterials for planarized ultrathin broadband circular
      polarizers.
AB  - Optical metamaterials are usually based on planarized, complex-shaped, resonant
      nano-inclusions. Three-dimensional geometries may provide a wider set of
      functionalities, including broadband chirality to manipulate circular
      polarization at the nanoscale, but their fabrication becomes challenging as their
      dimensions get smaller. Here we introduce a new paradigm for the realization of
      optical metamaterials, showing that three-dimensional effects may be obtained
      without complicated inclusions, but instead by tailoring the relative orientation
      within the lattice. We apply this concept to realize planarized, broadband
      bianisotropic metamaterials as stacked nanorod arrays with a tailored rotational
      twist. Because of the coupling among closely spaced twisted plasmonic
      metasurfaces, metamaterials realized with conventional lithography may
      effectively operate as three-dimensional helical structures with broadband
      bianisotropic optical response. The proposed concept is also shown to relax
      alignment requirements common in three-dimensional metamaterial designs. The
      realized sample constitutes an ultrathin, broadband circular polarizer that may
      be directly integrated within nanophotonic systems.

PMID- 22643898
TI  - Logic gates based on ion transistors.
AB  - Precise control over processing, transport and delivery of ionic and molecular
      signals is of great importance in numerous fields of life sciences. Integrated
      circuits based on ion transistors would be one approach to route and dispense
      complex chemical signal patterns to achieve such control. To date several types
      of ion transistors have been reported; however, only individual devices have so
      far been presented and most of them are not functional at physiological salt
      concentrations. Here we report integrated chemical logic gates based on ion
      bipolar junction transistors. Inverters and NAND gates of both npn type and
      complementary type are demonstrated. We find that complementary ion gates have
      higher gain and lower power consumption, as compared with the single transistor
      type gates, which imitates the advantages of complementary logics found in
      conventional electronics. Ion inverters and NAND gates lay the groundwork for
      further development of solid-state chemical delivery circuits.

PMID- 22643899
TI  - Unsupported boron-carbon sigma-coordination to platinum as an isolable snapshot
      of sigma-bond activation.
AB  - sigma-Complexes of transition metals-key intermediates in metal-mediated bond
      activation and homogeneous catalysis-have traditionally been isolable only when
      chelating or when one of the participating atoms is hydrogen. Here, by treating
      the Lewis-basic transition metal complex [Pt(PEt(3))(4)] with an electron-poor
      borirene, we isolate a complex with an unsupported borirene ligand bound, not
      through the unsaturated C=C bond, but exclusively via a B-C single bond. Using
      NMR spectroscopy, X-ray crystallography and density functional theory
      calculations, we show, herein, that coordination of the borirene ligand is based
      on electron donation from the B-C sigma bond to the metal, aided by a strong Pt
      to-B dative interaction. The complex is the first isolable non-agostic sigma
      complex featuring two p-block elements and has broad implications as a model for
      the metal-mediated activation of strong p-block-p-block sigma-bonds.

PMID- 22643900
TI  - Stable magnetostructural coupling with tunable magnetoresponsive effects in
      hexagonal ferromagnets.
AB  - The magnetostructural coupling between the structural and the magnetic transition
      has a crucial role in magnetoresponsive effects in a martensitic-transition
      system. A combination of various magnetoresponsive effects based on this coupling
      may facilitate the multifunctional applications of a host material. Here we
      demonstrate the feasibility of obtaining a stable magnetostructural coupling over
      a broad temperature window from 350 to 70 K, in combination with tunable
      magnetoresponsive effects, in MnNiGe:Fe alloys. The alloy exhibits a magnetic
      field-induced martensitic transition from paramagnetic austenite to ferromagnetic
      martensite. The results indicate that stable magnetostructural coupling is
      accessible in hexagonal phase-transition systems to attain the magnetoresponsive
      effects with broad tunability.

PMID- 22643901
TI  - The isolation of Pi1, an allele at the Pik locus which confers broad spectrum
      resistance to rice blast.
AB  - We report the isolation of Pi1, a gene conferring broad-spectrum resistance to
      rice blast (Magnaporthe oryzae). Using loss- and gain-of-function approaches, we
      demonstrate that Pi1 is an allele at the Pik locus. Like other alleles at this
      locus, Pi1 consists of two genes. A functional nucleotide polymorphism (FNP) was
      identified that allows differentiation of Pi1 from other Pik alleles and other
      non-Pik genes. A extensive germplasm survey using this FNP reveals that Pi1 is a
      rare allele in germplasm collections and one that has conferred durable
      resistance to a broad spectrum of pathogen isolates.

PMID- 22643902
TI  - SNP identification and allelic-specific PCR markers development for TaGW2, a gene
      linked to wheat kernel weight.
AB  - TaGW2, an orthologous gene of rice OsGW2, has been associated with kernel width
      and weight of bread wheat (Triticum aestivum). Difference in TaGW2 coding
      sequence was not found among different wheat varieties in previous researches. In
      this study, we found eight exons and seven introns in TaGW2 with a full-length
      cDNA sequence of 1,275 bp, which contains a conserved function domain and seven
      splice sites that shared homology with rice OsGW2. A single T-base insertion in
      the eighth exon of TaGW2 on chromosome 6A was detected in a large-kernel wheat
      variety, Lankaodali. This insertion mutation reduces the coding protein sequence
      from normal 424 amino acids (~47.2 kDa) to 328 amino acids (~37.1 kDa) by
      truncating 96 amino acids. The result was validated by identifying histidine
      tagged TaGW2 proteins encoded by both alleles of the mutant and the wild types in
      SDS-PAGE. Allele-specific PCR markers were developed based on the single
      nucleotide polymorphism (SNP) site. The SNP markers were genotyped for an F(2)
      segregation population from the cross of Lankaodali * Chinese Spring. Seed traits
      of F(2:3) families were evaluated in three different environments. The
      association analysis indicated that F(2:3) families with the mutated TaGW2 allele
      significantly increased kernel width (KW) and thousand-kernel weight (TKW), and
      slightly improved kernel length (KL). Using the SNP markers, another two
      varieties harbored the mutated TaGW2 allele were successfully identified from 22
      additional wheat varieties, and they both have large KW and TKW. Cloning and
      sequencing of the gene further confirmed the functions of the mutated allele of
      TaGW2 in the two large kernel varieties. The results suggested that TaGW2 may
      negatively regulate kernel size variation, which shares the same function as
      OsGW2 in rice. The successful development of SNP markers provides a useful tool
      for improving kernel yield in wheat.

PMID- 22643908
TI  - Is PhoR-PhoP partner fidelity strict? PhoR is required for the activation of the
      pho regulon in Streptomyces coelicolor.
AB  - Two-component regulatory systems play a key role in the cell metabolism
      adaptation to changing nutritional and environmental conditions. The fidelity
      between the two cognate proteins of a two-component system is important since it
      determines whether a specific response regulator integrates the signals
      transmitted by different sensor kinases. Phosphate regulation in Streptomyces
      coelicolor is mostly mediated by the PhoR-PhoP two-component system. Previous
      studies elucidated the mechanisms that control phosphate regulation as well as
      the genes directly regulated by the response regulator PhoP (pho regulon) in this
      organism. However, the role of the histidine kinase PhoR in Streptomyces
      coelicolor had not been unveiled so far. In this work, we report the
      characterization of a non-polar DeltaphoR deletion mutant in S. coelicolor that
      keeps its native promoter. Induction of the phoRP operon was dependent upon
      phosphorylation of PhoP, but the DeltaphoR mutant expressed phoP at a basal
      level. RT-PCR and reporter luciferase assays demonstrated that PhoR plays a key
      role in the activation of the pho regulon in this organism. Our results point
      towards a strict cognate partner specificity in terms of the phosphorylation of
      PhoP by PhoR thus corroborating the tight interaction between the two-components
      of this system.

PMID- 22643910
TI  - MicroRNA detection in prostate tumors by quantitative real-time PCR (qPCR).
AB  - MicroRNAs (miRNAs) are single-stranded, 18-24 nucleotide long, non-coding RNA
      molecules. They are involved in virtually every cellular process including
      development, apoptosis, and cell cycle regulation. MiRNAs are estimated to
      regulate the expression of 30% to 90% of human genes by binding to their target
      messenger RNAs (mRNAs). Widespread dysregulation of miRNAs has been reported in
      various diseases and cancer subtypes. Due to their prevalence and unique
      structure, these small molecules are likely to be the next generation of
      biomarkers, therapeutic agents and/or targets. Methods used to investigate miRNA
      expression include SYBR green I dye-based as well as Taqman-probe based qPCR. If
      miRNAs are to be effectively used in the clinical setting, it is imperative that
      their detection in fresh and/or archived clinical samples be accurate,
      reproducible, and specific. qPCR has been widely used for validating expression
      of miRNAs in whole genome analyses such as microarray studies. The samples used
      in this protocol were from patients who underwent radical prostatectomy for
      clinically localized prostate cancer; however other tissues and cell lines can be
      substituted in. Prostate specimens were snap-frozen in liquid nitrogen after
      resection. Clinical variables and follow-up information for each patient were
      collected for subsequent analysis. Quantification of miRNA levels in prostate
      tumor samples. The main steps in qPCR analysis of tumors are: Total RNA
      extraction, cDNA synthesis, and detection of qPCR products using miRNA-specific
      primers. Total RNA, which includes mRNA, miRNA, and other small RNAs were
      extracted from specimens using TRIzol reagent. Qiagen's miScript System was used
      to synthesize cDNA and perform qPCR (Figure 1). Endogenous miRNAs are not
      polyadenylated, therefore during the reverse transcription process, a poly(A)
      polymerase polyadenylates the miRNA. The miRNA is used as a template to
      synthesize cDNA using oligo-dT and Reverse Transcriptase. A universal tag
      sequence on the 5' end of oligo-dT primers facilitates the amplification of cDNA
      in the PCR step. PCR product amplification is detected by the level of
      fluorescence emitted by SYBR Green, a dye which intercalates into double stranded
      DNA. Specific miRNA primers, along with a Universal Primer that binds to the
      universal tag sequence will amplify specific miRNA sequences. The miScript Primer
      Assays are available for over a thousand human-specific miRNAs, and hundreds of
      murine-specific miRNAs. Relative quantification method was used here to quantify
      the expression of miRNAs. To correct for variability amongst different samples,
      expression levels of a target miRNA is normalized to the expression levels of a
      reference gene. The choice of a gene on which to normalize the expression of
      targets is critical in relative quantification method of analysis. Examples of
      reference genes typically used in this capacity are the small RNAs RNU6B, RNU44,
      and RNU48 as they are considered to be stably expressed across most samples. In
      this protocol, RNU6B is used as the reference gene.

PMID- 22643909
TI  - High-throughput sequencing discovery of conserved and novel microRNAs in Chinese
      cabbage (Brassica rapa L. ssp. pekinensis).
AB  - MicroRNAs (miRNAs) are a class of 21-24 nucleotide non-coding RNAs that down
      regulate gene expression by cleaving or inhibiting the translation of target gene
      transcripts. miRNAs have been extensively analyzed in a few model plant species
      such as Arabidopsis, rice and Populus, and partially investigated in other non
      model plant species. However, only a few conserved miRNAs have been identified in
      Chinese cabbage, a common and economically important crop in Asia. To identify
      novel and conserved miRNAs in Chinese cabbage (Brassica rapa L. ssp. pekinensis)
      we constructed a small RNA library. Using high-throughput Solexa sequencing to
      identify microRNAs we found 11,210 unique sequences belonging to 321 conserved
      miRNA families and 228 novel miRNAs. We ran a Blast search with these sequences
      against the Chinese cabbage mRNA database and found 2,308 and 736 potential
      target genes for 221 conserved and 125 novel miRNAs, respectively. The BlastX
      search against the Arabidopsis genome and GO analysis suggested most of the
      targets were involved in plant growth, metabolism, development and stress
      response. This study provides the first large scale-cloning and characterization
      of Chinese cabbage miRNAs and their potential targets. These miRNAs add to the
      growing database of new miRNAs, prompt further study on Chinese cabbage miRNA
      regulation mechanisms, and help toward a greater understanding of the important
      roles of miRNAs in Chinese cabbage.

PMID- 22643911
TI  - FTIR study of CO adsorption on Rh/MgO modified with Co, Ni, Fe, or CeO2 for the
      catalytic partial oxidation of methane.
AB  - The surface state of Rh/MgO catalysts modified with Co, Ni, Fe, or CeO(2) after
      the reduction and partial oxidation pretreatments as well as during the catalytic
      partial oxidation of methane has been investigated by FTIR of adsorbed CO. The
      results of CO adsorption on the reduced catalysts suggest the formation of Rh-M
      alloy on Rh-M/MgO (M = Co, Ni, Fe) and Rh particles partially covered with
      reduced ceria on Rh-CeO(2)/MgO. The strength of CO adsorption on Rh/MgO is
      weakened by the modification with Co, Ni, Fe, or CeO(2). Partial oxidation
      pretreatment of Rh/MgO leads to a significant decrease in the CO adsorption due
      to the oxidation of Rh. In contrast, on partially oxidized Rh-M/MgO (M = Co, Ni,
      Fe) and Rh-CeO(2)/MgO, the preferential oxidation of the surface M atoms or
      reduced ceria maintains the metallic Rh and preserves the CO adsorbed on the
      surface Rh atoms. The CO adsorption during the reaction of catalytic partial
      oxidation of methane on Rh/MgO and Rh-Ni/MgO is similar to that on the reduced
      catalysts. On the other hand, the CO adsorption during the reaction on Rh-Co/MgO,
      Rh-Fe/MgO, and Rh-CeO(2)/MgO is different from that on the reduced catalysts, and
      this is related to the structural change of these catalysts during the reaction.

PMID- 22643916
TI  - Pasteurella multocida: diseases and pathogenesis.
AB  - Pasteurella multocida is an enigmatic pathogen. It is remarkable both for the
      number and range of specific disease syndromes with which it is associated, and
      the wide range of host species affected. The pathogenic mechanisms involved in
      causing the different syndromes are, for the most part, poorly understood or
      completely unknown. The biochemical and serological properties of some organisms
      responsible for quite different syndromes appear to be similar. Thus, the
      molecular basis for host predilection remains unknown. The recent development of
      genetic manipulation systems together with the availability of multiple genome
      sequences should help to explain the association of particular pathological
      conditions with particular hosts as well as helping to elucidate pathogenic
      mechanisms.

PMID- 22643917
TI  - Evaluation of PRDM9 variation as a risk factor for recurrent genomic disorders
      and chromosomal non-disjunction.
AB  - Recent studies have identified PRDM9, a zinc finger (ZF) protein, as a key
      regulator of meiotic recombination. As both recurrent genomic disorders and
      chromosomal non-disjunction are known to be associated with specific unusual
      patterns of recombination, we hypothesized a possible link between PRDM9 ZF
      variation and susceptibility to microdeletion syndromes and/or trisomy. We
      sequenced the PRDM9 ZF domain in 271 parents of patients with de novo
      microdeletions of known parental origin (velocardiofacial syndrome, the 17q21.31
      microdeletion syndrome, Prader-Willi/Angelman syndrome and Williams-Beuren
      syndrome), and in 61 parents of individuals with a supernumerary X chromosome. We
      compared PRDM9 ZF genotype frequencies between parents in whose germ line the de
      novo rearrangement occurred and their spouses. We observed a significantly
      increased frequency (p = 0.006) of PRDM9 variants in parents who transmitted de
      novo 7q11.23 deletions to their offspring. These data suggest that certain PRDM9
      alleles may be associated with an increased susceptibility to recurrent 7q11.23
      microdeletions that cause Williams-Beuren syndrome. However, as the majority of
      parents who transmitted a de novo microdeletion/supernumerary X chromosome to
      their offspring have the common AA genotype, we conclude that none of the
      rearrangements we have studied are dependent on specific non-A PRDM9 alleles.

PMID- 22643930
TI  - Serotonin modulates the effects of Pavlovian aversive predictions on response
      vigor.
AB  - Updated theoretical accounts of the role of serotonin (5-HT) in motivation
      propose that 5-HT operates at the intersection of aversion and inhibition,
      promoting withdrawal in the face of aversive predictions. However, the specific
      cognitive mechanisms through which 5-HT modulates withdrawal behavior remain
      poorly understood. Behavioral inhibition in response to punishments reflects at
      least two concurrent processes: instrumental aversive predictions linking
      stimuli, responses, and punishments, and Pavlovian aversive predictions linking
      stimuli and punishments irrespective of response. In the current study, we
      examined to what extent 5-HT modulates the impact of instrumental vs Pavlovian
      aversive predictions on behavioral inhibition. We used acute tryptophan depletion
      to lower central 5-HT levels in healthy volunteers, and observed behavior in a
      novel task designed to measure the influence of Pavlovian and instrumental
      aversive predictions on choice (response bias) and response vigor (response
      latencies). After placebo treatment, participants were biased against responding
      on the button that led to punishment, and they were slower to respond in a
      punished context, relative to a non-punished context. Specifically, participants
      slowed their responses in the presence of stimuli predictive of punishments.
      Tryptophan depletion removed the bias against responding on the punished button,
      and abolished slowing in the presence of punished stimuli, irrespective of
      response. We suggest that this set of results can be explained by a role for 5-HT
      in Pavlovian aversive predictions. These findings suggest additional specificity
      for the influence of 5-HT on aversively motivated behavioral inhibition and
      extend recent models of the role of 5-HT in aversive predictions.

PMID- 22643931
TI  - Mitochondrial oxidative stress contributes differently to rat pancreatic islet
      cell apoptosis and insulin secretory defects after prolonged culture in a low non
      stimulating glucose concentration.
AB  - AIMS/HYPOTHESIS: Pancreatic beta cells chronically exposed to low glucose
      concentrations show signs of oxidative stress, loss of glucose-stimulated insulin
      secretion (GSIS) and increased apoptosis. Our aim was to confirm the role of
      mitochondrial oxidative stress in rat islet cell apoptosis under these culture
      conditions and to evaluate whether its reduction similarly improves survival and
      GSIS. METHODS: Apoptosis, oxidative stress-response gene mRNA expression and
      glucose-induced stimulation of mitochondrial metabolism, intracellular Ca(2+)
      concentration and insulin secretion were measured in male Wistar rat islets
      cultured for 1 week in RPMI medium containing 5-10 mmol/l glucose with or without
      manganese(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP) or N-acetyl-L-: cysteine
      (NAC). Oxidative stress was measured in islet cell clusters cultured under
      similar conditions using cytosolic and mitochondrial redox-sensitive green
      fluorescent protein (roGFP1/mt-roGFP1). RESULTS: Prolonged culture in 5 vs 10
      mmol/l glucose increased mt-roGFP1 (but not roGFP1) oxidation followed by beta
      cell apoptosis and loss of GSIS resulting from reduced insulin content,
      mitochondrial metabolism, Ca(2+) influx and Ca(2+)-induced secretion. Tolbutamide
      induced, but not high K(+)-induced, Ca(2+) influx was also suppressed. Under
      these conditions, MnTBAP, but not NAC, triggered parallel ~50-70% reductions in
      mt-roGFP1 oxidation and beta cell apoptosis, but failed to protect against the
      loss of GSIS despite significant improvement in glucose-induced and tolbutamide
      induced Ca(2+) influx. CONCLUSIONS/INTERPRETATION: Mitochondrial oxidative stress
      contributes differently to rat pancreatic islet cell apoptosis and insulin
      secretory defects during culture in a low glucose concentration. Thus, targeting
      beta cell survival may not be sufficient to restore insulin secretion when beta
      cells suffer from prolonged mitochondrial oxidative stress, e.g. in the context
      of reduced glucose metabolism.

PMID- 22643929
TI  - Epigenetics in the human brain.
AB  - Many cellular constituents in the human brain permanently exit from the cell
      cycle during pre- or early postnatal development, but little is known about
      epigenetic regulation of neuronal and glial epigenomes during maturation and
      aging, including changes in mood and psychosis spectrum disorders and other
      cognitive or emotional disease. Here, we summarize the current knowledge base as
      it pertains to genome organization in the human brain, including the regulation
      of DNA cytosine methylation and hydroxymethylation, and a subset of (altogether
      >100) residue-specific histone modifications associated with gene expression, and
      silencing and various other functional chromatin states. We propose that high
      resolution mapping of epigenetic markings in postmortem brain tissue or neural
      cultures derived from induced pluripotent cells (iPS), in conjunction with
      transcriptome profiling and whole-genome sequencing, will increasingly be used to
      define the molecular pathology of specific cases diagnosed with depression,
      schizophrenia, autism, or other major psychiatric disease. We predict that these
      highly integrative explorations of genome organization and function will provide
      an important alternative to conventional approaches in human brain studies, which
      mainly are aimed at uncovering group effects by diagnosis but generally face
      limitations because of cohort size.

PMID- 22643932
TI  - SNP in the genome-wide association study hotspot on chromosome 9p21 confers
      susceptibility to diabetic nephropathy in type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Parental type 2 diabetes mellitus increases the risk of diabetic
      nephropathy in offspring with type 1 diabetes mellitus. Several single nucleotide
      polymorphisms (SNPs) that predispose to type 2 diabetes mellitus have recently
      been identified. It is, however, not known whether such SNPs also confer
      susceptibility to diabetic nephropathy in patients with type 1 diabetes mellitus.
      METHODS: We genotyped nine SNPs associated with type 2 diabetes mellitus in
      genome-wide association studies in the Finnish population, and tested for their
      association with diabetic nephropathy as well as with severe retinopathy and
      cardiovascular disease in 2,963 patients with type 1 diabetes mellitus.
      Replication of significant SNPs was sought in 2,980 patients from three other
      cohorts. RESULTS: In the discovery cohort, rs10811661 near gene CDKN2A/B was
      associated with diabetic nephropathy. The association remained after robust
      Bonferroni correction for the total number of tests performed in this study (OR
      1.33 [95% CI 1.14, 1.56], p = 0.00045, p (36tests) = 0.016). In the meta
      analysis, the combined result for diabetic nephropathy was significant, with a
      fixed effects p value of 0.011 (OR 1.15 [95% CI 1.02, 1.29]). The association was
      particularly strong when patients with end-stage renal disease were compared with
      controls (OR 1.35 [95% CI 1.13, 1.60], p = 0.00038). The same SNP was also
      associated with severe retinopathy (OR 1.37 [95% CI 1.10, 1.69] p = 0.0040), but
      the association did not remain after Bonferroni correction (p (36tests) = 0.14).
      None of the other selected SNPs was associated with nephropathy, severe
      retinopathy or cardiovascular disease. CONCLUSIONS/INTERPRETATION: A SNP
      predisposing to type 2 diabetes mellitus, rs10811661 near CDKN2A/B, is associated
      with diabetic nephropathy in patients with type 1 diabetes mellitus.

PMID- 22643933
TI  - The thrifty phenotype hypothesis revisited.
AB  - Twenty years ago, Hales and Barker along with their co-workers published some of
      their pioneering papers proposing the 'thrifty phenotype hypothesis' in
      Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal
      programming could represent an important player in the origin of type 2 diabetes,
      the metabolic syndrome and cardiovascular disease (CVD) was met with great
      scepticism.More recently, their observations have been confirmed and expanded in
      many epidemiological and animal experimental studies, and human integrative
      physiological studies have provided insights into some of the underlying
      molecular mechanisms. Type 2 diabetes is a multiple-organ disease, and
      developmental programming, with its idea of organ plasticity, is a plausible
      hypothesis for a common basis for the widespread organ dysfunctions in type 2
      diabetes and the metabolic syndrome. Only two among the 45 known type 2 diabetes
      susceptibility genes are associated with low birthweight, indicating that the
      association between low birthweight and type 2 diabetes is mainly non-genetic.
      Prevention programmes targeting adult lifestyle factors seems unable to stop the
      global propagation of type 2 diabetes, and intensive glucose control is
      inadequate to reduce the excess CVD mortality in type 2 diabetic patients. Today,
      the thrifty phenotype hypothesis has been established as a promising conceptual
      framework for a more sustainable intergenerational prevention of type 2 diabetes.

PMID- 22643934
TI  - Is a positive nasal lysine-aspirin challenge test associated with a more severe
      phenotype of chronic rhinosinusitis and asthma?
AB  - BACKGROUND: Current guidelines recommend a greater use of aspirin challenge
      testing in the diagnosis of aspirin-intolerant rhinosinusitis and asthma, a
      disorder with high burden of illness and resistance to treatment. The indications
      for these tests and their clinical significance remain unclear. This study was
      designed to characterize the phenotype of patients with chronic rhinosinusitis
      with nasal polyposis (CRSwNP) with or without asthma undergoing a nasal lysine
      aspirin (L-ASA) challenge to evaluate which factors strongly predict a positive
      test. METHODS: Seventy-five patients with CRSwNP underwent nasal challenge with
      16 mg (total) of L-ASA after 30 minutes of acclimatization and diluent challenge.
      A positive challenge was defined as a 25% drop in total nasal volume measured by
      acoustic rhinometry. RESULTS: Twenty-three (31%) participants gave a history of
      aspirin intolerance and 38 (51%) had a positive nasal L-ASA challenge. Upper
      airway measures (CT scan score, olfaction, polyp grading, peak nasal inspiratory
      flow, nasal symptoms, etc.) and lower airway measures (methacholine provocative
      concentration required to produce a 20% drop in forced expiratory volume in 1
      second, effective special airway resistance, and spirometry) were not
      significantly worse in patients with a positive aspirin challenge. Test
      sensitivity was 48%, specificity was 52%, positive predictive value was 29%, and
      negative predictive value was 68%. A regression analysis identified forced
      expiratory flow at 25-75% (FEF(25-75)), history of aspirin intolerance, and
      duration of rhinosinusitis as significant predictors of a positive aspirin
      challenge. CONCLUSION: A positive response to nasal L-ASA challenge is not
      associated with a more severe phenotype of CRSwNP with or without asthma. A
      history of aspirin intolerance, duration of rhinosinusitis, and FEF(25-75)
      predict a greater response to aspirin.

PMID- 22643935
TI  - Computed nasal resistance compared with patient-reported symptoms in surgically
      treated nasal airway passages: a preliminary report.
AB  - BACKGROUND: Nasal airway obstruction (NAO) is a common health condition impacting
      mood, energy, recreation, sleep, and overall quality of life. Nasal surgery often
      addresses NAO but the results are sometimes unsatisfactory. Evaluating surgical
      treatment efficacy could be improved if objective tests were available that
      correlated with patient-reported measures of symptoms. The goal of this study was
      to develop methods for comparing nasal resistance computed by computational fluid
      dynamics (CFD) models with patient-reported symptoms of NAO using early data from
      a 4-year prospective study. METHODS: Computed tomography (CT) scans and patient
      reported scores from the Nasal Obstruction Symptom Evaluation (NOSE) scale and a
      visual analog scale (VAS) measuring unilateral airflow sensation were obtained
      pre- and postoperatively in two NAO patients showing no significant mucosal
      asymmetry who were successfully treated with functional nasal surgery, including
      septoplasty. Pre- and postsurgery CFD models were created from the CT scans.
      Numerical simulation of steady-state inspiratory airflow was used to calculate
      bilateral and unilateral CFD-derived nasal resistance (CFD-NR). RESULTS: In both
      subjects, NOSE and VAS scores improved after surgery, bilateral CFD-NR decreased,
      and unilateral CFD-NR decreased on the affected side. In addition, NOSE and VAS
      scores tracked with unilateral CFD-NR on the affected side. CONCLUSION: These
      preliminary results suggest a possible correlation between unilateral NR and
      patient-reported symptoms and imply that analysis of unilateral obstruction
      should focus on the affected side. A formal investigation of unilateral CFD-NR
      and patient-reported symptoms in a series of NAO patients is needed to determine
      if these variables are correlated.

PMID- 22643936
TI  - Nasal nitric oxide in a random sample of adults and its relationship to
      sensitization, cat allergen, rhinitis, and ambient nitric oxide.
AB  - BACKGROUND: There is conflicting evidence whether nasal nitric oxide (NO) is
      associated with current rhinitis and with other possible predictors. Most studies
      have been performed in clinical cohorts and there is a lack of studies based on a
      general population sample. The aim of the present study was to investigate
      predictors for levels of nasal nitric oxide (NO) in a general population.
      METHODS: The population consisted of 357 subjects from Gothenburg participating
      in the follow-up of the European Respiratory Health Survey in 1999-2001. All
      subjects completed an extensive respiratory questionnaire. Nasal NO was measured
      from one nostril at a time with a sampling rate of 50 mL/s for 16 seconds and the
      nasal NO concentration was determined as the mean value within the plateau phase.
      Mattress dust samples were collected for cats and mites in a subsample of
      subjects. Ambient and exhaled NO was also measured. The predictors for nasal NO
      were analyzed in multiple linear regression models. RESULTS: There was no
      relation between the levels of nasal NO and reporting current rhinitis. Nasal NO
      was significantly increased among those with high levels of IgE against cats and
      current smokers had significantly lower nasal NO. There was also a positive
      association between ambient NO and nasal NO. There were no significant
      associations between nasal NO and sex, age, or height, or between nasal NO and
      measured levels of cat antigen. CONCLUSION: In this general population sample we
      found no relation between current rhinitis and nasal NO levels. There was a clear
      association between sensitization to cat and nasal NO, but there was no relation
      to current exposure to cat allergen. Our data support that nasal NO has a limited
      value in monitoring upper airway inflammation.

PMID- 22643937
TI  - Comparison of lidocaine and levobupivacaine in transnasal fiberoptic
      laryngoscopy.
AB  - BACKGROUND: The anatomy of the nasal passages, pharynx, and larynx and evaluation
      of mucous membranes and laryngeal function is well observed by transnasal
      fiberoptic laryngoscopy (TFL). In this procedure, to provide good local
      infiltrative analgesia, medication such as anesthetics is important for the
      otolaryngologist. The aim of this study was to evaluate the efficacy of lidocaine
      (L) spray, compared with levobupivacaine solution, used for local anesthetic in
      patients undergoing TFL for complete examination. METHODS: Sixty-two subjects (39
      men and 23 women; mean age, 36 +/- 7 years) were enrolled in the study. Patients
      were randomly classified into two groups as levobupivacaine hydroclorur (LB) and
      L groups. A standard flexible transnasal fiberoptic 4.2-mm-diameter laryngoscope
      was passed through the nasal cavity and into the aerodigestive tract. Patients
      were asked to evaluate the intensity of the pain they experienced during the TFL,
      using a visual analog scale (VAS) and Ramsay sedation scale. RESULTS: Demographic
      data were similar in both groups. There was no difference in VAS and Ramsay
      scores between both groups (p > 0.05). CONCLUSION: Our findings indicated that
      topical levobupivacaine seems to be an effective medication for anesthesia of the
      nasal mucosa and may be used to allow complete examinations involving TFL.

PMID- 22643938
TI  - Frontal sinus cells: identification, prevalence, and association with frontal
      sinus mucosal thickening.
AB  - BACKGROUND: Frontal sinus cells (FSCs) are thought to be a potential cause of
      narrowing of frontal recess outflow. It remains unclear if FSCs are associated
      with frontal sinus mucosal thickening and chronic rhinosinusitis. The goal of the
      current study is to determine the prevalence of FSCs and their association with
      frontal sinus mucosal thickening. METHODS: All adult patients undergoing computed
      tomography (CT) scans of the paranasal sinuses at our institution between
      February and October 2010 were reviewed. All CT scans were evaluated for the
      presence of FSC (types 1-4) and association with frontal mucosal thickening. The
      secondary outcome measure was to examine interrater agreement between two raters
      who independently evaluated all CT scans. RESULTS: Analysis of 399 CT scans was
      performed with 71 scans excluded. The proportion of patients with FSC type 1 was
      26%, 6.4% was type 2 cells, 2.1% was type 3 cells, and 0% was type 4 cells. The
      odds ratio of mucosal thickening for type 1 FSCs was 15.9 (95% CI, 9.8-25.7),
      type 2 was 13.7 (95% CI, 6.7-27.8), and type 3 was 9.5 (95% CI, 3.0-30.2).
      Interrater agreement for the evaluation of mucosal thickening was high (kappa,
      0.69-0.76; p = 0.001). Agreement for the presence or absence of FSCs was moderate
      (kappa, 0.392; p = 0.001). CONCLUSION: There is a significant association of
      frontal sinus mucosal thickening with the presence of FSCs. Independent raters
      have moderate agreement when identifying the presence and type of FSCs.

PMID- 22643939
TI  - Expression and localization of aquaporin 1, 2, 3, 4, and 5 in human nasal mucosa.
AB  - BACKGROUND: Aquaporins (AQPs) are water-specific membrane channel proteins that
      regulate water homeostasis for cells and organisms. The purpose of this study was
      to elucidate the role of AQPs 1, 2, 3, 4, and 5 in normal and diseased human
      nasal mucosa. METHODS: Nasal polyps were obtained from eight patients with
      chronic rhinosinusitis (CRS). Inferior turbinate tissue was obtained from five
      patients with allergic rhinitis (AR) and from six patients with septal deviation
      (controls). Expression of AQP1-5 mRNA was examined using reverse transcriptase
      polymerase  chain reaction (RT-PCR) and immunoblotting, and tissue localization
      of AQP1-5 was studied by immunohistochemistry. Semiquantitative RT-PCR was used
      to investigate disease-specific changes in the expression in AQP1, -3, and -5
      mRNA. RESULTS: Expression of AQP1, -3,  -4, and -5 mRNA and AQP1-5 protein were
      confirmed in normal human nasal mucosa. Immunohistochemical studies revealed that
      AQP1 was localized in fibroblasts (especially in the subepithelial area) and
      endothelial cells of blood vessels, AQP2 was localized in the cytoplasm of
      epithelial  cells and acinar cells, AQP3 was localized in the basolateral sites
      of epithelial cells and acinar cells, AQP4 was localized in the basolateral sites
      of acinar cells, and AQP5 was localized in the apical sites of epithelial cells
      and acinar cells. Semiquantitative RT-PCR revealed that there  were no
      significant differences in the mRNA expression of AQP1, AQP3, and AQP5 among
      control, AR, and CRS patients. CONCLUSION: AQP1, -2, -3, -4, and -5 were present
      in normal human nasal mucosa. mRNA expression of AQP1, -3, and -5 did not change
      among control, AR, and  CRS patients.

PMID- 22643940
TI  - Down-regulation of gelsolin may play a role in the progression of inverted
      papilloma through an antiapoptotic mechanism.
AB  - BACKGROUND: Gelsolin is an actin-binding protein with multiple cellular functions
      including apoptosis and is reported to be down-regulated in various cancers and
      premalignant lesions. The objective of this study was to identify gelsolin and
      caspase-3 expression in inverted papilloma (IP) and investigate the role of
      gelsolin in the progression of IP related to apoptosis. METHODS: Specimens from
      30 patients with nondysplastic IP were retrieved. The percentage of surface
      epithelium covered with squamous metaplastic epithelium was assessed.
      Immunohistochemically demonstrated gelsolin and caspase-3 expression were
      compared between IP and adjacent control mucosa. We analyzed the correlations
      among gelsolin expression, caspase-3 expression, and the degree of squamous
      metaplasia in IP. RESULTS: The degree of squamous metaplasia of surface
      epithelium was inversely correlated with gelsolin (r = -0.610; p < 0.001) and
      caspase-3 expression (r = -0.433; p = 0.017). Gelsolin expression in IP was
      significantly lower than that in the control when >50% of surface epithelium
      showed squamous metaplasia (p = 0.015). Caspase-3 also showed diminished
      expression when >50% of surface epithelium had undergone squamous metaplasia (p =
      0.035). Gelsolin and caspase-3 expression showed no significant differences when
      the degree of squamous metaplasia was <=50%. Gelsolin and caspase-3 expression
      levels in IP had a positive relationship (r = 0.557; p = 0.001). CONCLUSION:
      Progression of IP may be related to an insidious decrease in caspase-3-mediated
      apoptosis, and down-regulated gelsolin expression may be correlated with the
      decrease in apoptosis, especially in more highly progressed IP in which >50% of
      surface epithelium has undergone squamous metaplasia.

PMID- 22643941
TI  - Effects of dexamethasone or methotrexate on chitinolytic activity in nasal
      polyps.
AB  - BACKGROUND: Chitin is a recognition element for tissue infiltration by innate
      cells implicated in allergy and immunity. This process can be negatively
      regulated by vertebrate chitinases. Chitinolytic activity is significantly
      increased in nasal polyps (NPs) compared with that in normal turbinate mucosa.
      Dexamethasone (DEX) or methotrexate (MTX) is an effective treatment for chronic
      inflammatory diseases. The aim of this study was to investigate the effects of
      DEX or MTX on chitinolytic activity in organ-cultured NPs. METHODS: NP tissues
      were cultured using an air-liquid interface culture model. Cultures were
      maintained for 24 hours in the absence or presence of DEX (10 or 100 micromolar)
      or MTX (10 or 100 micromolar). Acidic mammalian chitinase (AMCase) and
      chitotriosidase (ChT) activities in tissue samples were measured at a range of pH
      values by using the fluorogenic substrate 4-methylumbelliferyl-beta-(D)-N,N',N"
      triacetyl-chitotriose. RESULTS: AMCase and ChT chitinolytic activities were
      significantly lower in NPs treated with 100 micromolar DEX or 100 micromolar MTX
      than that in fresh or untreated NPs. AMCase chitinolytic activity tended to be
      lower in DEX-treated polyps than in MTX-treated polyps, although the difference
      was not statistically significant. CONCLUSION: DEX or MTX reduced chitinolytic
      activity in NPs. We suggest that DEX or MTX may inhibit the growth of NPs via
      local regulation of NP chitinolytic activity.

PMID- 22643942
TI  - The united allergic airway: connections between allergic rhinitis, asthma, and
      chronic sinusitis.
AB  - BACKGROUND: The united allergic airway is a theory that connects allergic
      rhinitis (AR), chronic rhinosinusitis, and asthma, in which seemingly disparate
      diseases, instead of being thought of separately, are instead viewed as arising
      from a common atopic entity. OBJECTIVE: This article describes patients with such
      diseases; explores ideas suggesting a unified pathogenesis; elucidates the
      various treatment modalities available, emphasizing nasal corticosteroids and
      antihistamines; and provides an update of the literature. METHODS: A literature
      review was conducted. CONCLUSION: The aggregation of research suggests that AR,
      asthma, and chronic rhinosinusitis are linked by the united allergic airway, a
      notion that encompasses commonalities in pathophysiology, epidemiology, and
      treatment.

PMID- 22643943
TI  - Reduced olfactory bulb volume and diminished olfactory function in total
      laryngectomy patients: a prospective longitudinal study.
AB  - BACKGROUND: This study was designed to investigate the effects of total
      laryngectomy on olfactory bulb (OB) volume and olfactory function prospectively.
      A prospective, longitudinal, randomized study was performed. METHODS: Fifteen
      subjects with advanced cancer of the larynx were recruited. The OB volume was
      measured preoperatively and 6 months postoperatively using magnetic resonance
      imaging (MRI) and olfactory function was assessed using the Connecticut
      Chemosensory Clinical Research Center (CCCRC) test. A detailed
      otorhinolaryngological examination was conducted and abnormalities that could
      potentially cause olfactory dysfunction were excluded. An experienced radiologist
      segmented the MRI coronal slices manually for OB volume measurements. RESULTS:
      The difference between the right and left OB volumes was not significant. OB
      volume decreased significantly 6 months postoperatively, from 64.2 to 47.1 mm(3)
      (p < 0.001). The CCCRC test results, scored out of 8, decreased significantly
      from 5.6 to 2.4 (p < 0.001) and all patients were either anosmic or hyposmic.
      CONCLUSION: This longitudinal prospective study was the first to examine the
      cessation of olfactory stimulation in olfactory deficiency resulting from OB
      functional and structural changes.

PMID- 22643944
TI  - Antibiotics in septoplasty: evidence or habit?
AB  - BACKGROUND: Antibiotic prophylaxis for surgical procedures is a common practice
      among otorhinolaryngologists. Most American Rhinology Society members use
      antibiotics routinely in septoplasties, even though the need for this practice in
      rhinological surgery is controversial. This study was designed to assess the
      necessity of antibiotic prophylaxis in septoplasties in relation to surgical
      outcome and postoperative complications. METHODS: In a prospective randomized
      clinical trial we evaluated 630 subjects who underwent septoplasty according to
      the technique already described by the authors. Patients were divided into three
      groups: group A, no antibiotic prophylaxis; group B, antibiotics (cefazolin at
      1.0 g i.v.) only at anesthetic induction; group C, antibiotics both at anesthetic
      induction (cefazolin at 1.0 g i.v.) and postoperatively (oral amoxicillin at 1 g
      every 12 hours) for 7 days. Pre- and postoperative patients' scores on the Nasal
      Obstruction Septoplasty Effectiveness (NOSE) questionnaire were compared to
      assess the improvement of nasal symptoms after surgery. Postoperative pain, nasal
      bleeding, septal hematoma/abscess, fever, and nausea/vomiting were recorded.
      Nasal endoscopy was performed 14 days postoperatively to quantify purulent
      rhinorrhea. RESULTS: An improvement of postoperative nasal symptoms on the NOSE
      questionnaire was recorded with respect to preoperative score. No significant
      difference was found among the groups with regard to postoperative pain, fever,
      nausea/vomiting, and nasal bleeding. No case of hematoma or septal abscess was
      noticed. No significant difference in purulent nasal discharge was found among
      the groups. CONCLUSION: Septal surgery with early removal of nasal packing is a
      clean-contaminated procedure and does not require routine antibiotic prophylaxis
      because of the low infection risk.

PMID- 22643945
TI  - Surfactant improves irrigant penetration into unoperated sinuses.
AB  - BACKGROUND: Saline irrigations are proving to be a valuable intervention in the
      treatment of chronic sinusitis. The use of surfactants is a well established
      additive to topical treatments known to reduce surface tension and may prove to
      be a simple, nonoperative intervention  to improve intrasinus douching
      penetration. METHODS: Six 30-mL, flat-bottomed medicine cups with circular holes
      cut through the bottom center and varying in diameter from 1 to 6 mm were created
      with punch biopsies. Water, saline, saline/dye, and saline/dye/surfactant were 
      compared for maximum holding pressure via these modeled ostia. Holding pressures
      also were determined for cups with septal mucosa fused to the bottom with holes
      ranging from 1 to 6 mm. In addition, analysis was carried out with blood and
      blood/surfactant. Finally, five thawed, fresh-frozen  cadaver heads were
      evaluated before any sinus surgery with water/dye and water/dye/surfactant for
      intrasinus penetration. RESULTS: Surfactant significantly improved the ability of
      all solutions to penetrate ostia in both the plastic cup and fused septal mucosa
      model. All  nonsurfactant-containing solutions were not statistically different
      from one another, nor did surfactant change the ostial penetration of blood.
      Surfactant significantly improved the ability of sinus irrigant to penetrate
      unoperated sinus cavities (3.12 vs 3.5, p = .021). CONCLUSIONS: The addition of
      surfactant to saline irrigation improves ostial penetration in undissected and
      undiseased cadavers. This has practical implications for unoperated patients
      seeking care for sinus-related symptoms in that we have now described a method
      for improving topical treatment of  target sinus mucosa prior to surgical
      intervention.

PMID- 22643946
TI  - Contamination of sinus irrigation devices: a review of the evidence and clinical
      relevance.
AB  - BACKGROUND: The use of saline and topical medications in the treatment of chronic
      rhinosinusitis (CRS) is now common practice among otolaryngologists. Although
      high-level studies have consistently shown the benefit of saline in symptom
      improvement of CRS patients, to date, only lower-level evidence exists advocating
      a benefit of other topical medications. METHODS: Recently, increased interest has
      emerged surrounding the devices used to deliver such therapies with mounting
      evidence consistently showing contamination with pathogenic organisms such as
      Staphylococcus aureus and Pseudomonas aeruginosa. RESULTS: In addition, the
      potential for such contamination to cross-infect sinus cavities and lead to
      postoperative infections is also of concern. CONCLUSION: This review examines the
      current evidence available concerning the issue of contamination and its clinical
      relevance and offers the otolaryngologist advice on patient education when
      dispensing such devices.

PMID- 22643947
TI  - Central presentation of postviral olfactory loss evaluated by positron emission
      tomography scan: a pilot study.
AB  - BACKGROUND: Postviral olfactory loss after upper respiratory tract infection
      (URI) is not uncommon. However, its exact location and nature are not fully
      understood. Although it is likely to be caused by a direct damage of olfactory
      epithelium, a damage of the central pathway has also been suspected as its
      possible mechanism. This study will show basal metabolism in the brain of
      patients with postviral olfactory loss using fluorodeoxyglucose-positron emission
      tomography (FDG PET). METHODS: Nine patients with postviral olfactory dysfunction
      were enrolled. All of the patients had neither apparent sinusitis nor rhinitis.
      All of them recalled causative URI and temporal connection with development of
      their olfactory loss. After olfactory function tests using the butanol threshold
      test and smell identification test confirmed olfactory impairment, FDG PET
      studies were performed during a rest state. The cerebral metabolic abnormality
      was compared between the patients and age/gender-matched healthy controls using a
      voxel-wised analysis. RESULTS: In comparison with healthy controls, the patients
      showed a significant hypometabolism in the right piriform cortex and bilateral
      amygdala and parahippocampal areas where the olfactory neurons primarily project.
      Furthermore, hypometabolism was also shown in the bilateral insular cortices,
      medial and lateral temporal cortex where the olfactory information is integrated
      to produce the sensation. Increased metabolism was not found in any brain area.
      CONCLUSION: This study showed that the postviral olfactory loss is likely to be
      associated with decreased metabolism in the specific brain regions where the
      olfactory information is received and integrated.

PMID- 22643948
TI  - The effect of anatomically directed topical steroid drops on frontal recess
      patency after endoscopic sinus surgery: a prospective randomized single blind
      study.
AB  - BACKGROUND: The failure rate for frontal sinusotomy is higher than that of
      overall endoscopic sinus surgery (ESS). To prevent frontal sinus obstruction,
      systemic or topical steroids are commonly used, but systemic steroid therapy can
      cause significant morbidity and topical sprays can not be distributed to the
      frontal ostium. This study was designed to determine the efficacy of anatomically
      directed topical steroid drops in reducing frontal ostium stenosis compared with
      topical steroid sprays after ESS. METHODS: A prospective, randomized, single
      blind study was conducted in 43 patients (77 nasal cavities) who had undergone
      ESS, including frontal sinusotomy. Twenty-one patients (39 nasal cavities) used
      steroid drops applied with the Mygind technique, and 22 patients (38 nasal
      cavities) used steroid sprays for 8 weeks postoperatively. The patency of the
      frontal ostium was evaluated endoscopically 3 months postoperatively. RESULTS:
      The study included 29 men and 14 women (mean age, 48.2 years; range, 19-62
      years). Endoscopic scores in terms of polypoid change, edema, and scar in the
      middle meatus and frontal recess were not significantly different between the
      groups, although the drop group showed a tendency to superior scores when
      compared with the spray group (p > 0.05). The frontal sinus patency of the drop
      group was significantly higher than of the spray group (p < 0.05). CONCLUSION:
      Topical steroid drops using the Mygind technique led to a 16% improvement in
      frontal sinus patency rates in 3 month after ESS in this study compared with
      postoperative topical steroid use.

PMID- 22643949
TI  - Sinonasal perivascular epithelioid cell tumor: benign or malignant neoplasm?
AB  - BACKGROUND: Neoplasms showing perivascular epithelioid cell differentiation
      (PEComas) are uncommon tumors of the sinonasal tract. They are often misdiagnosed
      as angiomyolipoma or a simple benign tumor or polyp. We present a further case of
      a sinonasal PEComa and review the literature in an attempt to ascertain their
      malignant potential. METHODS: Published evidence on invasiveness and
      characteristics were defined on systematic review. MEDLINE and EMBASE were
      searched from 1966 and 1980, respectively, to week 3 of December 2010.
      Publications reporting PEComa or angiomyolipoma were sought. Only those
      describing a sinonasal origin were included. Demographics, anatomic site, local
      invasion, recurrence rates, and mortality were recorded. A case report of a
      locally invasive intranasal PEComa is described. RESULTS: In addition to the case
      we present, 12 case reports were located (n = 13). The mean age of patients was
      59.6 (SD, 14.98 years) years. The location was within the right sinonasal tract
      in 54% of cases, the left sinonasal tract in 38% of cases, and not reported in 8%
      of cases. Treatment focused on local surgical excision and this was achieved
      endoscopically in 100% of cases. Recurrence rate was 8%. Mean follow-up was 17.4
      (SD, 20.68 months) months. Invasion was noted in 23% of cases. There was a single
      death recorded. CONCLUSION: PEComas of the paranasal sinuses and skull base
      appear to have a biological behavior different from simple benign angiomyolipomas
      reported elsewhere in the body. PEComa may be more intermediate or malignant in
      clinical behavior.

PMID- 22643950
TI  - A multiallergen and miniscreen can change primary care provider diagnosis and
      treatment of rhinitis.
AB  - BACKGROUND: A number of studies suggested that limited economical airborne
      allergy screening can successfully predict true respiratory allergy and be of use
      to primary care providers (PCPs) in improving the accuracy of their differential
      diagnosis and treatment of allergic rhinitis. More accurate diagnosis would lead
      to proper use of intranasal corticosteroids, intranasal antihistamines, and oral
      antihistamines. However, to date, there have been no reports of an actual
      application of the screens by PCPs. This study was designed to measure the
      potential impact of providing a limited multiallergen and miniscreen (MAMS) by in
      vitro allergy testing on PCP diagnosis and treatment of rhinitis, properly
      differentiating seasonal allergic rhinitis, perennial allergic rhinitis,
      vasomotor rhinitis, and mixed rhinitis. METHODS: Two hundred adult and adolescent
      patients who presented to PCPs for rhinitis symptoms were enrolled from July to
      November of 2007. They signed informed consent and a serum specimen for MAMS was
      obtained. The PCPs answered a questionnaire concerning their diagnosis and
      treatment before and after the MAMS results were revealed to the PCP. RESULTS:
      The PCPs changed or modified the original diagnosis in 139 of 200 patients.
      Originally, 182 subjects had an allergic rhinitis diagnosis. After the results of
      the MAMS were known, 113 continued with an allergic rhinitis diagnosis. Vasomotor
      or nonallergic rhinitis diagnoses increased from 18 to 87 cases. CONCLUSION: Use
      of MAMS can help PCPs make a more accurate diagnosis and offer better therapy to
      patients with rhinitis.

PMID- 22643951
TI  - Olfaction in athletes with concussion.
AB  - BACKGROUND: Moderate to severe traumatic brain injuries (TBIs) commonly lead to
      olfactory dysfunction; it is, however, unclear whether and to what degree mild
      TBI such as concussions, which are common sports injuries, affect olfactory
      function. We therefore aimed to evaluate smell function in athletes who sustained
      one or more sport concussions in a cross-sectional design. METHODS: Twenty-two
      University-level football players with one or multiple concussions and 13 control
      athletes without a history of concussion participated. We measured olfactory
      function by using the Sniffin' Sticks test to assess subjects' ability to
      discriminate and identify odors as well as their detection thresholds. In
      addition, we assessed odor intensity and pleasantness. RESULTS: We used number of
      concussions and time since the last concussion as independent variables and
      measure of olfactory function as dependent variables. Although we did not observe
      any significant effect of the number of concussions, athletes with a longer delay
      from time of concussion scored significantly weaker than more recently concussed
      subjects on the odor identification test and on an aggregate olfactory score.
      Accordingly, we observed a significant negative linear correlation between the
      odor identification score and the time elapsed since the last concussion.
      CONCLUSION: These findings suggest a possible degenerative effect of concussions
      on olfactory function.

PMID- 22643952
TI  - Retrieval of projectile foreign bodies from the paranasal sinuses and skull base.
AB  - BACKGROUND: Penetrating trauma to the paranasal sinuses and skull base with
      retained foreign bodies represents a unique challenge for head and neck surgeons.
      Management of these injuries is complicated by associated injuries and the
      proximity to vital neurovascular structures. This study was designed to review
      the clinical experience with retained sinonasal and skull base projectile foreign
      bodies at a single academic tertiary care institution. METHODS: A retrospective
      review of patients who suffered penetrating trauma to the head with retained
      metallic foreign bodies in the paranasal sinuses and/or skull base between
      January 2002 and August 2011 was performed at a single academic medical center.
      RESULTS: There were 599 patients who suffered penetrating trauma to the head and
      neck, with 13 patients having retained metallic foreign bodies in the sinuses
      and/or skull base, mostly bullets or nails. Ten patients underwent urgent (n = 5)
      or delayed (n = 5) removal of foreign bodies accessible without compromise of
      adjacent structures either through an endoscopic or open approach. Three patients
      had multiple foreign bodies that were not removed. Three patients experienced
      traumatic cerebrospinal fluid fistula managed with either conservative measures
      (n = 2) or intraoperative repair at the time of foreign body retrieval (n = 1).
      All patients received prophylactic antibiotic coverage. No patients suffered
      infectious complications such as sinusitis from retained foreign bodies.
      CONCLUSION: Although not all retained foreign bodies after penetrating trauma to
      the head require removal, those that are safely accessible and at risk for
      infectious complications should be recovered. The timing and approach of
      retrieval are dictated by the clinical scenario.

PMID- 22643953
TI  - Inferior turbinate composite graft for repair of nasal septal perforation.
AB  - BACKGROUND: Repair of nasal septal perforations is one of the most challenging
      procedures in nasal surgery. The aim of this prospective clinical study was to
      determine the efficacy of using an inferior turbinate composite graft (ITCG) for
      the repair of nasal septal perforation. METHODS: Between 2009 and 2011, 27
      consecutive patients with nasal septal perforation underwent endoscopy-assisted,
      endonasal septal perforation repair by using an ITCG alone or in combination with
      bipedicled mucosal advancement flap. RESULTS: Complete closure of the perforation
      was achieved in 24 of 27 (88.8%) patients, and incomplete closure was observed in
      2 patients with medium-sized perforation and 1 patient with large perforation.
      CONCLUSION: The ITCG technique provides three-layer repair of the defect under no
      tension in closure of small perforations located anteriorly, posterior
      perforations with mucosal atrophy, or previous unsuccessful surgical repair. In
      graft-depleted revision rhinoplasty cases with small-sized septal perforations,
      this technique provides a simple solution with autogenous grafts. In cases
      involving larger perforations, the ITCG technique can easily be combined with
      bipedicled flap and allows for more options to solve a challenging problem.
      Current data from this prospective study suggest that this surgical technique may
      be used in the repair of nasal septal perforation.

PMID- 22643955
TI  - Staphylococcus aureus. Letters to the editor.

PMID- 22643957
TI  - Pseudomeningoceles of the sphenoid sinus masquerading as sinus pathology.

PMID- 22643958
TI  - Physicochemical study of spiropyran-terthiophene derivatives: photochemistry and
      thermodynamics.
AB  - The photochemistry and thermodynamics of two terthiophene (TTh) derivatives
      bearing benzospiropyran (BSP) moieties, 1-(3,3"-dimethylindoline-6'
      nitrobenzospiropyranyl)-2-ethyl 4,4"-didecyloxy-2,2':5',2"-terthiophene-3'
      acetate (BSP-2) and 1-(3,3"-dimethylindoline-6'-nitrobenzospiropyranyl)-2-ethyl
      4,4"-didecyloxy-2,2':5',2"-terthiophene-3'-carboxylate (BSP-3), differing only by
      a single methylene spacer unit, have been studied. The kinetics of
      photogeneration of the equivalent merocyanine (MC) isomers (MC-2 and MC-3,
      respectively), the isomerisation properties of MC-2 and MC-3, and the
      thermodynamic parameters have been studied in acetonitrile, and compared to the
      parent, non-TTh-functionalised, benzospiropyran derivative, BSP-1. Despite the
      close structural similarity of BSP-2 and BSP-3, their physicochemical properties
      were found to differ significantly; examples include activation energies (E(a(MC
      2)) = 75.05 kJ mol(-1), E(a(MC-3)) = 100.39 kJ mol(-1)) and entropies of
      activation (DeltaS = 43.38 J K(-1) mol(-1), DeltaS = 37.78 J K(-1) mol(-1)) for
      the thermal relaxation from MC to BSP, with the MC-3 value much closer to the
      unmodified MC-1 value (46.48 J K(-1) mol(-1)) for this latter quantity. The
      thermal relaxation kinetics and solvatochromic behaviour of the derivatives in a
      range of solvents of differing polarity (ethanol, dichloromethane, acetone,
      toluene and diethyl ether) are also presented. Differences in the estimated
      values of these thermodynamic and kinetic parameters are discussed with reference
      to the molecular structure of the derivatives.

PMID- 22643964
TI  - Rat mesentery exteriorization: a model for investigating the cellular dynamics
      involved in angiogenesis.
AB  - Microvacular network growth and remodeling are critical aspects of wound healing,
      inflammation, diabetic retinopathy, tumor growth and other disease conditions.
      Network growth is commonly attributed to angiogenesis, defined as the growth of
      new vessels from pre-existing vessels. The angiogenic process is also directly
      linked to arteriogenesis, defined as the capillary acquisition of a perivascular
      cell coating and vessel enlargement. Needless to say, angiogenesis is complex and
      involves multiple players at the cellular and molecular level. Understanding how
      a microvascular network grows requires identifying the spatial and temporal
      dynamics along the hierarchy of a network over the time course of angiogenesis.
      This information is critical for the development of therapies aimed at
      manipulating vessel growth. The exteriorization model described in this article
      represents a simple, reproducible model for stimulating angiogenesis in the rat
      mesentery. It was adapted from wound-healing models in the rat mesentery, and is
      an alternative to stimulate angiogenesis in the mesentery via i.p. injections of
      pro-angiogenic agents. The exteriorization model is attractive because it
      requires minimal surgical intervention and produces dramatic, reproducible
      increases in capillary sprouts, vascular area and vascular density over a
      relatively short time course in a tissue that allows for the two-dimensional
      visualization of entire microvascular networks down to single cell level. The
      stimulated growth reflects natural angiogenic responses in a physiological
      environment without interference of foreign angiogenic molecules. Using
      immunohistochemical labeling methods, this model has been proven extremely useful
      in identifying novel cellular events involved in angiogenesis. Investigators can
      readily correlate the angiogenic metrics during the time course of remodeling
      with time specific dynamics, such as cellular phenotypic changes or cellular
      interactions.

PMID- 22643965
TI  - The assessment and application of an approach to noncovalent interactions: the
      energy decomposition analysis (EDA) in combination with DFT of revised dispersion
      correction (DFT-D3) with Slater-type orbital (STO) basis set.
AB  - An assessment study is presented about energy decomposition analysis (EDA) in
      combination with DFT including revised dispersion correction (DFT-D3) with Slater
      type orbital (STO) basis set. There has been little knowledge about the
      performance of the EDA + DFT-D3 concerning STOs. In this assessment such an
      approach was applied to calculate noncovalent interaction energies and their
      corresponding components. Complexes in S22 set were used to evaluate the
      performance of EDA in conjunction with four representative types of GGA
      functionals of DFT-D3 (BP86-D3, BLYP-D3, PBE-D3 and SSB-D3) with three STO basis
      sets ranging in complexity from DZP, TZ2P to QZ4P. The results showed that the
      approach of EDA + BLYP-D3/TZ2P has a better performance not only in terms of
      calculating noncovalent interaction energy quantitatively but also in analyzing
      corresponding energy components qualitatively. This approach (EDA + BLYP-D3/TZ2P)
      was thus applied further to two representative large-system complexes including
      porphine dimers and fullerene aggregates to gain a better insight into binding
      characteristics.

PMID- 22643966
TI  - Halogen bond tunability II: the varying roles of electrostatic and dispersion
      contributions to attraction in halogen bonds.
AB  - In a previous study we investigated the effects of aromatic fluorine substitution
      on the strengths of the halogen bonds in halobenzene...acetone complexes (halo =
      chloro, bromo, and iodo). In this work, we have examined the origins of these
      halogen bonds (excluding the iodo systems), more specifically, the relative
      contributions of electrostatic and dispersion forces in these interactions and
      how these contributions change when halogen sigma-holes are modified. These
      studies have been carried out using density functional symmetry adapted
      perturbation theory (DFT-SAPT) and through analyses of intermolecular correlation
      energies and molecular electrostatic potentials. It is found that electrostatic
      and dispersion contributions to attraction in halogen bonds vary from complex to
      complex, but are generally quite similar in magnitude. Not surprisingly,
      increasing the size and positive nature of a halogen's sigma-hole dramatically
      enhances the strength of the electrostatic component of the halogen bonding
      interaction. Not so obviously, halogens with larger, more positive sigma-holes
      tend to exhibit weaker dispersion interactions, which is attributable to the
      lower local polarizabilities of the larger sigma-holes.

PMID- 22643967
TI  - Fractal dimension as a measure of surface roughness of G protein-coupled
      receptors: implications for structure and function.
AB  - Protein surface roughness is a structural property associated with ligand-protein
      and protein-protein binding interfaces. In this work we apply for the first time
      the concept of surface roughness, expressed as the fractal dimension, to address
      structure and function of G protein-coupled receptors (GPCRs) which are an
      important group of drug targets. We calculate the exposure ratio and the fractal
      dimension for helix-forming residues of the beta(2) adrenergic receptor
      (beta(2)AR), a model system in GPCR studies, in different conformational states:
      in complex with agonist, antagonist and partial inverse agonists. We show that
      both exposure ratio and roughness exhibit periodicity which results from the
      helical structure of GPCRs. The pattern of roughness and exposure ratio of a
      protein patch depends on its environment: the residues most exposed to membrane
      are in general most rough whereas parts of receptors mediating interhelical
      contacts in a monomer or protein complex are much smoother. We also find that
      intracellular ends (TM3, TM5, TM6 and TM7) which are relevant for G protein
      binding and thus receptor signaling, are exposed but smooth. Mapping the values
      of residual fractal dimension onto receptor 3D structures makes it possible to
      conclude that the binding sites of orthosteric ligands as well as of cholesterol
      are characterized with significantly higher roughness than the average for the
      whole protein. In summary, our study suggests that identification of specific
      patterns of roughness could be a novel approach to spot possible binding sites
      which could serve as original drug targets for GPCRs modulation.

PMID- 22643968
TI  - Electric field effect on (6,0) zigzag single-walled aluminum nitride nanotube.
AB  - Structural, electronic, and electrical responses of the H-capped (6,0) zigzag
      single-walled aluminum nitride nanotube was studied under the parallel and
      transverse electric fields with strengths 0-140 * 10(-4) a.u. by using density
      functional calculations. Geometry optimizations were carried out at the B3LYP/6
      31G* level of theory using a locally modified version of the GAMESS electronic
      structure program. The dipole moments, atomic charge variations, and total energy
      of the (6,0) zigzag AlNNT show increases with increase in the applied external
      electric field strengths. The length, tip diameters, electronic spatial extent,
      and molecular volume of the nanotube do not significantly change with increasing
      electric field strength. The energy gap of the nanotube decreases with increases
      of the electric field strength and its reactivity is increased. Increase of the
      ionization potential, electron affinity, chemical potential, electrophilicity,
      and HOMO and LUMO in the nanotube with increase of the applied parallel electric
      field strengths shows that the parallel field has a much stronger interaction
      with the nanotube with respect to the transverse electric field strengths.
      Analysis of the parameters indicates that the properties of AlNNTs can be
      controlled by the proper external electric field.

PMID- 22643969
TI  - Can Satraplatin be hydrated before the reduction process occurs? The DFT
      computational study.
AB  - Hydration reactions of two anticancer Pt(IV) complexes JM149 and JM216
      (Satraplatin) were studied computationally together with the hydration of the
      Pt(II) complex JM118, which is a product of the Satraplatin reduction.
      Thermodynamic and kinetic parameters of the reactions were determined at the
      B3LYP/6-311++G(2df.2pd)//B3LYP/6-31 + G(d)) level of theory. The water solution
      was modeled using the COSMO implicit solvation model, with cavities constructed
      using Klamt's atomic radii. It was found that hydration of the Pt(IV) complexes
      is an endergonic/endothermic reaction. It follows the (pseudo)associative
      mechanism is substantially slower (k ~ 10(-11) s(-1)) than the corresponding
      reaction of Pt(II) analogues ((k ~ 10(-5) s(-1)). Such a low value of the
      reaction constant signifies that the hydration of JM149 and Satraplatin is with
      high probability a kinetically forbidden reaction. Similarly to JM149 and
      Satraplatin, the hydration of JM118 is an endothermic/endoergic reaction. On the
      other hand, the kinetic parameters are similar to those of cisplatin Zimmermann
      et al. (J Mol Model 17:2385-2393, 2011), allowing the hydration reaction to occur
      at physiological conditions. These results suggest that in order to become active
      Satraplatin has to be first reduced to JM118, which may be subsequently hydrated
      to yield the active species.

PMID- 22643970
TI  - Molecular design of modified polyacrylamide for the salt tolerance.
AB  - In our work, three kinds of functional monomers were selected to modify
      polyacrylamide (PAM) or partially hydrolyzed polyacrylamide (HPAM) by molecular
      dynamics simulation so as to achieve the stronger salt-tolerance of modified HM
      HPAM. The radius of gyration (R (g)), the hydrodynamic radius (R (H)), the
      effective length (L (ef)) and the intrinsic viscosity ([eta]) for modified PAM or
      HPAM were studied in aqueous solutions with different ionic strength at 298 K.
      The results showed that modified HM-HPAM has a stronger salt tolerance and the
      salt tolerance increases gradually from HM-HPAM1 to HM-HPAM3 because the monomers
      with different steric hindrance would reduce the curliness of molecular chains
      and, consequently, improve the salt tolerance. So, introducing the steric
      hindrance monomer into polymer will increase the salt tolerance of the polymer
      and it is indicated that the simulated results agree with the experimental
      results very well. Furthermore, the radial distribution function (RDF) has been
      used to investigate the effect of NaCl on the hydration of the -COO- groups of
      the HM-HPAM from microscopic view.

PMID- 22643971
TI  - Molecular structure and effects of intermolecular hydrogen bonding on the
      vibrational spectrum of trifluorothymine, an antitumor and antiviral agent.
AB  - In the present work, the experimental and the theoretical vibrational spectra of
      trifluorothymine were investigated. The FT-IR (400-4000 cm(-1)) and MU-Raman
      spectra (100-4000 cm(-1)) of trifluorothymine in the solid phase were recorded.
      The geometric parameters (bond lengths and bond angles) and vibrational
      frequencies of the title molecule in the ground state were calculated using ab
      initio Hartree-Fock (HF) method and density functional theory (B3LYP) method with
      the 6-31++G(d,p) and 6-311++G(d,p) basis sets for the first time. The optimized
      geometric parameters and the theoretical vibrational frequencies were found to be
      in good agreement with the corresponding experimental data and with results found
      in the literature. Vibrational frequencies were assigned based on the potential
      energy distribution using the VEDA 4 program. The dimeric form of
      trifluorothymine was also simulated to evaluate the effect of intermolecular
      hydrogen bonding on the vibrational frequencies. It was observed that the
      stretching modes shifted to lower frequencies, while the in-plane and out-of
      plane bending modes shifted to higher frequencies due to the intermolecular N-H?O
      hydrogen bonds.

PMID- 22643972
TI  - Understanding the molecular mechanism of the broad and potent neutralization of
      HIV-1 by antibody VRC01 from the perspective of molecular dynamics simulation and
      binding free energy calculations.
AB  - VRC01 is one of the most broadly and potently neutralizing HIV-1 antibodies known
      it has been shown to neutralize 91 % of the tested primary isolate Env
      pseudoviruses by recognizing the viral envelope glycoprotein gp120. To explore
      the mechanism of HIV-1 neutralization by VRC01 and thus obtain valuable
      information for vaccine design, we performed molecular dynamics simulations and
      binding free energy calculations for apo-VRC01, apo-gp120, and the gp120-VRC01
      complex. For gp120, residue energy decomposition analysis showed that the hotspot
      residues Asn280, Lys282, Asp368, Ile371, and Asp457 are located in three primary
      loops, including the CD4-binding loop, loop D, and loop V5. For VRC01, the
      hotspot residues Trp47, Trp50, Asn58, Arg61, Gln64, Trp100, and Tyr91 mainly come
      from CDR2 of the heavy chain. By decomposing the binding free energy into
      different components, intermolecular van der Waals interactions and nonpolar
      solvation were found to dominate the binding process. Principal component
      analysis of loops D and V5, which are related to neutralization resistance,
      indicated that these two areas have a larger conformational space in apo-gp120
      compared to bound gp120. A comparison of three representative structures from the
      cluster analysis of loops D and V5 indicated that changes primarily occur at the
      tip of loop V5, and are caused by fluctuations in the terminal Glu1 residue of
      the antibody. This information can be used to guide the design of vaccines and
      small molecule inhibitors.

PMID- 22643973
TI  - Validation of a novel secretion modification region (SMR) of HIV-1 Nef using
      cohort sequence analysis and molecular modeling.
AB  - The HIV-1 accessory protein Nef plays an active role in the pathogenesis of AIDS
      by its numerous cellular interactions that facilitate the release of virus
      particles. This 27 kDa protein is required for maintenance of the viral
      replication in HIV, and is also known to contribute to immune evasion, blocking
      of apoptosis in virus-infected cells and enhancement of virus infectivity. Nef
      has been shown to be secreted and is present on the surface of virus-infected
      cells. Recent studies from our laboratory have shown that the Nef protein is
      secreted from nef-transfected and HIV-1-infected cells in small exosome-like
      vesicles (40-100 nm diam.) that do not contain virions. We have identified three
      amino-terminal domains of Nef as necessary for secretion: (i) the four arginine
      residues (17,19,21, 22) comprising the basic region; (ii) the phosphofurin acidic
      cluster sequence (PACS) composed of four glutamic acid residues (61-64); (iii) a
      previously unknown motif spanning amino acid residues 65-69 (VGFPV) which we
      named the secretion modification region (SMR). In this study, we have used
      population-based phylogeny data and sequence analysis to characterize the
      conservation of the Nef SMR domain that regulates vesicle secretion. We have
      performed in silico computational chemistry analysis involving molecular dynamic
      structure modeling of mutations in the SMR motif. Sequence analysis of Nef from
      HIV-1-infected patients, including slow progressors (SP), long term progressors
      (LTP) and long term non-progressors (LTNP) demonstrated 99 % conservation of the
      Nef SMR motif. Computational analysis including modeling of wild-type HIV-1 Nef
      and V66A Nef SMR mutant using structural homology and molecular dynamics of
      ligand-associated interactions indicated significant structural changes in the
      Nef mutant, thus supporting the importance of the SMR domain for mediating Nef
      vesicle secretion.

PMID- 22643974
TI  - Some insights into the binding mechanism of Aurora B kinase gained by molecular
      dynamics simulation.
AB  - Aurora B kinase is essential in the process of mitosis, and its overexpression
      has been reported to be associated with a number of solid tumors. We therefore
      carried out molecular docking, molecular dynamics, and molecular mechanics
      Poisson-Boltzmann/surface area (MM-PBSA) calculations on several structurally
      diverse inhibitors (pentacyclic, pyrimidine, quinazoline, and pyrrolopyridine
      derivatives) and Aurora B kinase to explore the structural and chemical features
      responsible for the binding recognition mechanism. Molecular simulations reveal
      that the binding site mainly consists of six binding regions (sites A-F). We have
      identified that sites B and C are required for optimum binding in Aurora B
      inhibitor complexes, sites A and F are needed to improve pharmacokinetic
      properties, while sites D and E lead to enhanced stability. We verified that
      hydrogen bonding to the hinge region and hydrophobic contact with the conserved
      hydrophobic pocket are of critical importance in the systems studied.
      Specifically, the amino acids Glu171, Phe172, and Ala173 in the hinge region and
      Leu99, Val107, and Leu223 in the conserved hydrophobic pocket probably account
      for the high binding affinities of these systems, as shown by hydrogen-bonding
      analysis and energy decomposition analysis. Hydrophobic contact with Phe172 is
      also in agreement with experimental data. In addition, the MM-PBSA calculations
      reveal that the binding of these inhibitors to Aurora B kinase is mainly driven
      by van der Waals/nonpolar interactions. The findings of this study should help to
      elucidate the binding pattern of Aurora B inhibitors and aid in the design of
      novel active ligands.

PMID- 22643975
TI  - Molecular mechanical perspective on halogen bonding.
AB  - The nature and strength of halogen bonding in halo molecule-Lewis base complexes
      were studied in terms of molecular mechanics using our recently developed
      positive extra-point (PEP) approach, in which the sigma-hole on the halogen atom
      is represented by an extra point of positive charge. The contributions of the
      sigma-hole (i.e., positively charged extra point) and the halogen atom to the
      strength of this noncovalent interaction were clarified using the atomic
      parameter contribution to the molecular interaction (APCtMI) approach. The
      molecular mechanical results revealed that the halogen bond is electrostatic and
      van der Waals in nature, and its strength depends on three types of interaction:
      (1) the attractive electrostatic interaction between the sigma-hole and the Lewis
      base, (2) the repulsive electrostatic interaction between the negative halogen
      atom and the Lewis base, and (3) the repulsive/attractive van der Waals
      interactions between the halogen atom and the Lewis base. The strength of the
      halogen bond increases with increasing sigma-hole size (i.e., magnitude of the
      extra-point charge) and increasing halogen atom size. The van der Waals
      interaction's contribution to the halogen bond strength is most favorable in
      chloro complexes, whereas the electrostatic interaction is dominant in iodo
      complexes. The idea that the chloromethane molecule can form a halogen bond with
      a Lewis base was revisited in terms of quantum mechanics and molecular mechanics.
      Although chloromethane does produce a positive region along the C-Cl axis, basis
      set superposition error corrected second-order Moller-Plesset calculations showed
      that chloromethane-Lewis base complexes are unstable, producing halogen-Lewis
      base contacts longer than the sum of the van der Waals radii of the halogen and
      O/N atoms. Molecular mechanics using the APCtMI approach showed that
      electrostatic interactions between chloromethane and a Lewis base are unfavorable
      owing to the high negative charge on the chlorine atom, which overcomes the
      corresponding favorable van der Waals interactions.

PMID- 22643977
TI  - Active components of frequently used beta-blockers from the aspect of
      computational study.
AB  - The aim of this study is to investigate the active components of representative
      drugs for blood pressure regulation by applying quantum mechanical computer codes
      and comparison of the same for the sake of obtaining knowledge about the
      properties associated with the electronic structure of given molecules. The study
      included three well-known, but not theoretically investigated enough, active
      components of beta-blockers: acebutolol, metoprolol and atenolol. The results are
      in agreement with the experimental data and were used for initial assumptions
      concerning the degradation of these compounds.

PMID- 22643976
TI  - Stochastic simulation of structural properties of natively unfolded and denatured
      proteins.
AB  - A new simulation strategy based on a stochastic process has been developed and
      tested to study the structural properties of the unfolded state of proteins at
      the atomistic level. The procedure combines a generation algorithm to produce
      representative uncorrelated atomistic microstructures and an original relaxation
      method to minimize repulsive non-bonded interactions. Using this methodology, a
      set of 14 unfolded proteins, including seven natively unfolded proteins as well
      as seven "classical" proteins experimentally described in denaturation
      conditions, has been investigated. Comparisons between the calculated and
      available experimental values of several properties, at hydrodynamic and atomic
      level, used to describe the unfolded state, such as the radius of gyration, the
      maximum length, the hydrodynamic radius, the diffusion coefficient, the
      sedimentation coefficient, and the NMR chemical shifts, reflect a very good
      agreement. Furthermore, our results indicate that the relationship between the
      radius of gyration and the hydrodynamic radius deviates from the Zimm's theory of
      polymer dynamics for random coils, as was recently observed using single-molecule
      fluorescent methods. Simulations reveal that the interactions between atoms
      separated by three chemical bonds (1-4 interactions) play a crucial role in the
      generation process, suggesting that the unfolded state is essentially governed by
      bonding and short-range non-bonding interactions.

PMID- 22643978
TI  - Ligation of water to magnesium chelates of biological importance.
AB  - Water binding to several Mg(2+) chelates, ethylenediamine, ethylenediamine-N,N'
      diacetate, porphyrin, chlorophyll a and bacteriochlorophyll a, to form five- and
      six-coordinate complexes is studied by means of density functional theory. The
      results obtained for magnesium chelates are compared with the properties of the
      respective aqua complexes and the influence of the permittivity of environment on
      the ligand binding energies is discussed. Although the most common coordination
      number of Mg(2+) is six, in the tetrapyrrolic chelates it is reduced to five
      because the accommodation of the sixth water ligand results in no gain in energy.
      This is in line with the experimental observations made for coordination of
      chlorophylls in vivo. The binding between Mg(2+) and water is mostly of
      electrostatic nature, which is supported by the finding that its energy is
      correlated both with the electron density of the chelator and with electrostatic
      potential determined at the ligand binding site.

PMID- 22643979
TI  - Selectivity of labeled bromoethylamine for protein alkylation.
AB  - Alkylation of cysteine residues has been used extensively for characterization of
      proteins and their mode of action in biological systems, research endeavors that
      are at the core of proteomics. Treatment with a simple alkylating agent such as
      [2-(13)C] bromoethylamine would result in labeled thialysine at the epsilon
      position. This chemical modification of proteins would allow investigations via
      both (13)C NMR spectroscopy and mass spectrometry. However [2-(13)C] labeled
      bromoethylamine is not available commercially. We investigated its synthesis at
      acid pH with the goal of obtaining singly labeled bromoethylamine and
      understanding the mechanistic details of the reaction. Based on our experimental
      and theoretical results, bromination of [2-(13)C] labeled ethanolamine in acidic
      conditions takes place via exclusive attack of the nucleophile (HBr) at the
      hydroxyl bearing C. Moreover, hydrogen bonding guides the nucleophilic attack,
      resulting in no label scrambling of the bromoethylamine product. Protein
      alkylation at cysteine residue with the synthesized Br(13)CH(2)CH(2)NH(2)-HBr is
      successful. Ab initio calculations in which CH(3)SH serves as a model for the
      cysteine residue suggest that in gas phase intermolecular attack by the sulfur
      bearing nucleophile is favored over the intramolecular substitution by the amino
      group by 15.4 kJ mol(-1). Solution modeling shows that the trend is preserved at
      basic pH, which is the experimental one, but is reversed at neutral pH.

PMID- 22643980
TI  - Tuning electronic structure and photophysical properties of [Ir(ppy)2(py)2]+ by
      substituents binding in pyridyl ligand: a computational study.
AB  - Iridium (III) 2-phenylpyridine (ppy) complexes with two suitable monodentate L
      ligands [Ir(ppy)2(L)2]+ (ppy = 2-phenylpyridine, py = pyridine, L = 4-pyCN 1, 4
      pyCHO 2, 4-pyCl 3, py 4, 4-pyNH2 5) were studied by density functional theory
      (DFT) and time-dependent DFT methods. The influences of ligands L on the
      electronic structure and photophysical properties were investigated in detail.
      The compositions and energy levels of the lowest unoccupied molecular orbital
      (LUMO) are changed more significantly than those of the highest occupied
      molecular (HOMO) by tuning L ligands. With the electronegativity decrease of L
      ligands 4-pyCN > 4-pyCHO > 4-pyCl > py > 4-pyNH2, the LUMO distributing changes
      from py to ppy, and the absorptions have an obvious red shift. The calculated
      results showed that the transition character of the absorption and emission can
      be changed by adjusting the electronegativity of the L ligands. In addition, no
      solvent effect was observed in the absorptions and emissions.

PMID- 22643981
TI  - Density functional theory calculations on the thermodynamic properties of
      polynitrosoprismanes.
AB  - A series of polynitrosoprismanes, C(6)H(6 - n )(NO)( n ) (n = 1-6), considered as
      high energy density compounds (HEDCs), have been designed computationally. We
      calculated the electronic structures, the heats of formation, the specific
      enthalpies of combustion, the bond dissociation energies, and the strain energies
      of the title compounds using density functional theory (DFT) with the 6-311G**
      basis set. It was found that the DeltaE (LUMO-HOMO) values of the title compounds
      decrease as the number of nitroso groups increase, and the energy gaps of the
      prismane derivatives are much lower than that of TATB. Their high positive heats
      of formation indicate that polynitrosoprismanes can store a great deal of energy.
      Furthermore, the HOFs for the nitrosoprismane series were observed to decrease
      until three nitroso groups were connected to the prismane skeleton. For the
      polynitrosoprismanes, the trigger bond was confirmed to be the C-C bond in the
      skeleton. According to our calculations, all nitrosoprismanes appear to have
      large strain energies, and these calculations can provide basic information that
      may prove useful for the molecular design of novel high energy density materials.

PMID- 22643982
TI  - A "crutch to assist in gaining an honest living": dispensary shopkeeping by
      Scottish general practitioners and the responses of the British medical elite,
      ca. 1852-1911.
AB  - This article examines the practice among general practitioners in Scotland of
      keeping shops for dispensary and retail purposes in the late nineteenth century.
      It demonstrates that while doctors kept such open shops in these areas in order
      to subsidize their income in a crowded medical market, they argued that
      shopkeeping allowed them to provide medical care in communities where the
      population was otherwise too poor to pay for such care. The article compares
      shopkeeping to medical "covering" and assesses the medical hierarchy's reactions
      to shopkeeping doctors via disciplinary actions taken against some of these
      doctors by the General Medical Council (GMC). These actions provoked an organized
      protest among hundreds of doctors (some of it channeled through the British
      Medical Association), which challenged the methods of the GMC in determining
      acceptable professional medical standards.

PMID- 22643983
TI  - Sauvons les Bebes: child health and U.S. humanitarian aid in the First World War
      era.
AB  - From 1917 to 1923, the American Red Cross organized an array of long-term child
      health projects in Europe as part of its larger wartime and post-war humanitarian
      efforts. Across the continent, the organization established child health clinics,
      better baby shows, playgrounds, fresh air camps, and courses for women on infant
      and child hygiene. Hundreds of U.S. doctors, nurses, and other child welfare
      professionals traveled to Europe to administer these programs. These activities
      call attention to American efforts to reform the health of European youth and, in
      so doing, to reshape European medicine and European society more broadly.
      Moreover, they suggest the importance of child-centered medical relief-and the
      history of medicine more broadly-to the history of U.S. foreign relations.

PMID- 22643984
TI  - "A startling new chemotherapeutic agent": pediatric infectious disease and the
      introduction of sulfonamides at Baltimore's Sydenham Hospital.
AB  - Using pediatric patient records from Baltimore's Sydenham Hospital, this article
      explores the adoption of sulfa drugs in pediatrics. It discusses how clinicians
      dealt with questions of dosing and side effects and the impact of the
      sulfonamides on two diagnoses in children: meningococcal meningitis and
      pneumonia. The care of infants and children with infectious diseases made demands
      on physicians and nurses that differed from those facing clinicians treating
      adult patients. The article demonstrates the need to distinguish between
      pediatric and adult medical history. It suggests that the new therapeutics
      demanded more intense bedside care and enhanced laboratory facilities, and as a
      result paved the way for the adoption of penicillin. Finally, it argues that
      patient records and the published medical literature must be examined together in
      order to gain a full understanding of how transformations in medical practice and
      therapeutics occur.

PMID- 22643985
TI  - Methods and management: NIH administrators, federal oversight, and the Framingham
      Heart Study.
AB  - This article explores the 1965 controversy over the Framingham Heart Study in the
      midst of growing oversight into the management of science at the National
      Institutes of Health (NIH). It describes how, beginning in the early 1960s,
      federal overseers demanded that NIH administrators adopt particular management
      styles in administering programs and how these growing pressures led
      administrators to favor investigative pursuits that allowed for easy prospective
      accounting of program payoffs, especially those based on experimental methods
      designed to examine discrete interventions or outcomes of interest. In light of
      this changing managerial culture within the NIH, the Framingham study and other
      population laboratories-with their bases in observation and in open-ended study
      designs-became harder for NIH administrators to justify and defend.

PMID- 22643999
TI  - Modeling the geographic distribution of serious mental illness in New Zealand.
AB  - PURPOSE: This study aims to estimate, apply, and validate a model of the risk of
      serious mental illness (SMI) in local service areas throughout New Zealand.
      METHODS: The study employs a secondary analysis of data from the Te Rau Hinengaro
      Mental Health Survey of 12,992 adults aged 16 years and over from the household
      population. It uses small area estimation (SAE) methods involving: (1) estimation
      of a logistic model of risk of SMI; (2) use of the foregoing model for computing
      estimates, using census data, for District Board areas; (3) validation of
      estimates against an alternative indicator of SMI prevalence. RESULTS: The model
      uses age, ethnicity, marital status, employment, and income to predict 92.2 % of
      respondents' SMI statuses, with a specificity of 95.9 %, sensitivity of 16.9 %,
      and an AUC of 0.73. The resulting estimates for the District Board areas ranged
      between 4.1 and 5.7 %, with confidence intervals from +/-0.3 to +/-1.1 %. The
      estimates demonstrated a correlation of 0.51 (p = 0.028) with rates of
      psychiatric hospitalization. CONCLUSIONS: The use of SAE methods demonstrated the
      capacity for deriving local prevalence rates of SMI, which can be validated
      against an available indicator.

PMID- 22644001
TI  - The alpha-test: rapid cell-free CD4 enumeration using whole saliva.
AB  - There is an urgent need for affordable CD4 enumeration to monitor HIV disease.
      CD4 enumeration is out of reach in resource-limited regions due to the time and
      temperature restrictions, technical sophistication, and cost of reagents, in
      particular monoclonal antibodies to measure CD4 on blood cells, the only
      currently acceptable method. A commonly used cost-saving and time-saving
      laboratory strategy is to calculate, rather than measure certain blood values.
      For example, LDL levels are calculated using the measured levels of total
      cholesterol, HDL, and triglycerides. Thus, identification of cell-free correlates
      that directly regulate the number of CD4(+) T cells could provide an accurate
      method for calculating CD4 counts due to the physiological relevance of the
      correlates. The number of stem cells that enter blood and are destined to become
      circulating CD4(+) T cells is determined by the chemokine CXCL12 and its receptor
      CXCR4 due to their influence on locomotion. The process of stem cell locomotion
      into blood is additionally regulated by cell surface human leukocyte elastase
      (HLE(CS)) and the HLE(CS)-reactive active alpha(1)proteinase inhibitor
      (alpha(1)PI, alpha(1)antitrypsin, SerpinA1). In HIV-1 disease, alpha(1)PI is
      inactivated due to disease processes. In the early asymptomatic categories of HIV
      1 disease, active alpha(1)PI was found to be below normal in 100% of untreated
      HIV-1 patients (median=12 MUM, and to achieve normal levels during the
      symptomatic categories. This pattern has been attributed to immune inactivation,
      not to insufficient synthesis, proteolytic inactivation, or oxygenation. We
      observed that in HIV-1 subjects with >220 CD4 cells/MUl, CD4 counts were
      correlated with serum levels of active alpha(1)PI (r(2)=0.93, p<0.0001, n=26) and
      inactive alpha(1)PI (r(2)=0.91, p<0.0001, n=26). Administration of alpha(1)PI to
      HIV-1 infected and uninfected subjects resulted in dramatic increases in CD4
      counts suggesting alpha(1)PI participates in regulating the number of CD4(+) T
      cells in blood. With stimulation, whole saliva contains sufficient serous exudate
      (plasma containing proteinaceous material that passes through blood vessel walls
      into saliva) to allow measurement of active alpha(1)PI and the correlation of
      this measurement is evidence that it is an accurate method for calculating CD4
      counts. Briefly, sialogogues such as chewing gum or citric acid stimulate the
      exudation of serum into whole mouth saliva. After stimulating serum exudation,
      the activity of serum alpha(1)PI in saliva is measured by its capacity to inhibit
      elastase activity. Porcine pancreatic elastase (PPE) is a readily available
      inexpensive source of elastase. PPE binds to alpha(1)PI forming a one-to-one
      complex that prevents PPE from cleaving its specific substrates, one of which is
      the colorimetric peptide, succinyl-L-Ala-L-Ala-L-Ala-p-nitroanilide (SA(3)NA).
      Incubating saliva with a saturating concentration of PPE for 10 min at room
      temperature allows the binding of PPE to all the active alpha(1)PI in saliva. The
      resulting inhibition of PPE by active alpha(1)PI can be measured by adding the
      PPE substrate SA(3)NA. (Figure 1). Although CD4 counts are measured in terms of
      blood volume (CD4 cells/MUl), the concentration of alpha(1)PI in saliva is
      related to the concentration of serum in saliva, not to volume of saliva since
      volume can vary considerably during the day and person to person. However,
      virtually all the protein in saliva is due to serum content, and the protein
      content of saliva is measurable. Thus, active alpha(1)PI in saliva is calculated
      as a ratio to saliva protein content and is termed the alpha(1)PI Index. Results
      presented herein demonstrate that the alpha(1)PI Index provides an accurate and
      precise physiologic method for calculating CD4 counts.

PMID- 22644002
TI  - Pseudoephedrine induces sperm abnormalities, lower sperm counts and increased
      apoptosis in rat testis.
AB  - Pseudoephedrine, an over-the-counter drug, is commonly used for the treatments of
      asthma, nasal congestion, and obesity. Furthermore, it can be used as a
      psychostimulant drug if taken in large doses; however, there have been no reports
      on its effects on reproduction. The aim of this study was therefore to
      investigate the effects of pseudoephedrine administration on sperm morphology,
      sperm concentration and apoptotic activity in the rat testis. Rats were
      administered intraperitoneally (IP) with pseudoephedrine at 120 mg/kg for the
      acute group and 80 mg/kg, IP, once daily for 15 days for the chronic group, while
      a control group was treated with vehicle. The percentages of normal sperm
      morphology were significantly decreased in both acute and chronic groups when
      compared with controls while the total sperm count was significantly decreased in
      the acute group. Apoptotic activities were increased significantly in both
      pseudoephedrine-treated groups. The results indicate that pseudoephedrine can
      induce sperm abnormalities, decrease sperm numbers and increase apoptotic
      activity in the testis of rats if taken at high doses. The results of this study
      suggest that the users of pseudoephedrine in medical treatments need to be aware
      of its potential toxicity involving spermatogenesis.

PMID- 22644000
TI  - Use of general practitioners versus mental health professionals in six European
      countries: the decisive role of the organization of mental health-care systems.
AB  - OBJECTIVE: To investigate patterns of use of general practitioners (GPs) and/or
      mental health professionals (MHPs) for mental health reasons, across six European
      countries, and the extent to which these patterns of use are associated with
      differences in mental health-care delivering systems. METHODS: Data are based on
      the European Study of the Epidemiology of Mental Disorders (ESEMeD): a cross
      sectional survey of a representative sample of 8,796 non-institutionalized adults
      from six European countries, conducted between 2001 and 2003 using computer
      assisted interviews with the CIDI-3.0. Countries were classified into: MHP- for
      countries where access to medical professionals tends to predominate (Belgium,
      France, Italy), and MHP+ where access to non-medical MHPs predominates (Germany,
      Spain, The Netherlands). RESULTS: Among respondents consulting GPs and/or MHPs in
      the past year (n = 1,019), respondents from the MHP- group more often consulted
      GPs (68 vs. 55 % in MHP+ group), GPs and psychiatrists (23 vs. 14 %). People from
      the MHP+ group more often used MHPs only (45 vs. 32 %), GPs and non-medical MHPs
      (16 vs. 8 %). GPs from the MHP+ group were more inclined to refer patients to
      MHPs. Factors associated with use of GPs versus MHPs were: being over 49 years,
      not highly educated, lower income and suffering from mood or severe mental
      disorders. CONCLUSIONS: Differences in the use of GPs versus MHPs are markedly
      linked to individual as well as organizational factors. Interventions are needed,
      in countries fostering medical access, to reimburse sessions with non-medical
      MHPs and improve cooperation between professionals to obtain better practice in
      access to care.

PMID- 22644003
TI  - Surgical treatment of type 2 diabetes mellitus.

PMID- 22644004
TI  - Expected value of foveal thickness in macular edema in Mexican patients with
      diabetes.
AB  - BACKGROUND: The tomographic cut-off point to detect macular edema uses an
      international reference of retinal thickness, which is greater than that in our
      population. We undertook this study to identify the expected value of central
      subfield mean thickness (CSMT) in Mexican patients with diabetes with clinically
      significant macular edema (CSME) and the proportion in which using only the
      tomographic cut-off point for clinical macular edema (>300 MUm) could overlook
      the diagnosis. METHODS: We carried out an observational, analytical,
      crosssectional and prospective study. Eyes of diabetic patients with CSME
      (January 2006-June 2007) with a fluorescein angiography and optical coherence
      tomography were included. The sample was divided according to angiographic type:
      monofocal (group 1), multifocal (group 2), or diffuse (group 3). The mean of CSMT
      of each group was weighed by the proportion represented by each group to
      calculate the all-type expected value. The proportion of eyes with CSMT = 300 MUm
      was identified. RESULTS: Ninety-three eyes were included. Mean age was 60.9
      years; there were 57 females (61.3%). Forty-one eyes were assigned to group 1
      (44.1%, CSMT 210.63 MUm), 31 to group 2 (33.3%, CSMT 279.65 MUm), and 21 to group
      3 (22.6%, CSMT 327.14 MUm). The expected value of CSMT was 259.9 MUm, 37.75% over
      the normal reference in the study population and 23% over the American reference.
      CSMT was <300 MUm in 79.6% of the eyes (95% CI 71.4-87.8). CONCLUSIONS: The
      expected value of CSMT in Mexican patients with diabetes with CSME was within the
      range internationally regarded as subclinical. Using local references of CSMT is
      recommended to avoid overlooking the diagnosis of CSME and overestimating its
      treatment effect.

PMID- 22644005
TI  - Minilaparotomy vs. laparoscopic cholecystectomy: results of a randomized clinical
      trial.
AB  - BACKGROUND: Currently, laparoscopic cholecystectomy is considered the gold
      standard for treatment of gallstones with advantages in regard to postoperative
      pain, hospital stay, early return to activities of daily living and acceptable
      cosmetic results. Open cholecystectomy in the form of minilaparotomy may be an
      effective alternative for the management of symptomatic cholelithiasis. We
      undertook this study to compare the results of laparoscopic cholecystectomy and
      minilaparotomy cholecystectomy techniques. methods: We conducted a randomized
      clinical trial between January 2009 and December 2009. We included patients with
      symptomatic cholelithiasis divided into two groups: group A--minilaparotomy and
      group B--laparoscopic cholecystectomy. End-point variables were age, gender, pre-
      and postoperative diagnosis, operative time, conversion or extension, hospital
      stay, complications and pain. Statistical analysis included Fisher's exact test,
      chi(2) test and Student t test. RESULTS: There were 88 patients with
      cholelithiasis: 37 men and 51 women. Mean age was 45.65 years. There were 45
      patients in Group A and 43 patients in Group B. Mean operative time was 79.02 min
      for minilaparotomy and 86.04 min for laparoscopic cholecystectomy (p = 0.33).
      Average hospital stay was 2.75 days for minilaparotomy and of 2.02 days for
      laparoscopy (p = 0.60). Complications of minilaparotomy were demonstrated in 6.6%
      of patients and for laparoscopic cholecystectomy in 16.3% of patients (p = 0.16).
      There were three extensions and five conversions. CONCLUSIONS: Minilaparotomy
      cholecystectomy has results similar to laparoscopic cholecystectomy.

PMID- 22644006
TI  - Comparison of transumbilical approach versus infraumbilical incision for the
      repair of umbilical hernia in adults.
AB  - BACKGROUND: Surgical management of umbilical hernias is proposed in the vast
      majority of cases. The typical approaches make a semilunar incision above the
      umbilicus. The aim of this study is evaluate the surgical approach with two
      different incisions, the transumbilical approach and the infra-umbilical
      approach. METHODS: Included in the study were 82 consecutive patients with
      diagnosis of umbilical hernia. Variables related to demographic characteristics,
      surgical operation, and cosmetic results were evaluated. Patients were randomized
      into two groups; transumbilical or infra-umbilical approach. Statistical analysis
      was carried out to evaluate complications, recurrences and aspects of the
      surgical scar. RESULTS: The study included group A (42 patients) and group B (40
      patients). The most frequent symptom was pain in both groups. Complications were
      similar in both groups with four (9.5%) in group A and eight (19%) in group B (RR
      0.53, 95% CI 0.17-1.61, p = 0.24). Cosmetic results were classified as good in
      the vast majority of patients in group A (p 0.001). No recurrences or mortality
      have been reported so far in both studied groups. CONCLUSION: We described an
      uncommon technique of incision with the aim of improving cosmetic results. Our
      results are in concordance with randomized clinical trials with the same
      technique with no recurrence or mortality to date. Cosmetic results in our
      patients using the transumbilical approach were clearly superior.

PMID- 22644007
TI  - Prevalence of nonalcoholic fatty liver disease in subjects with metabolic
      syndrome.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic
      liver disease. Metabolic syndrome (MetS) is an important predictor of NAFLD. Due
      to the increase of MetS in Mexico, a population-based cross-sectional study was
      conducted to estimate the prevalence of NAFLD. METHODS: One hundred ninety eight
      subjects with MetS were randomly selected from 1006 subjects and were invited to
      participate in the estimation of the prevalence of NAFLD. MetS was diagnosed
      following the criteria of the National Cholesterol Education Program (ATPIII
      NCEP). Abdominal ultrasound was performed and left, right and caudate lobes were
      assessed according to size, echogenicity and hepatic borders. NAFLD was
      classified as mild, moderate and severe according to its echogenicity and
      visualization of the diaphragm and intrahepatic vessel borders. Prevalence of
      NAFLD was estimated with 95% confidence intervals (95% CI). RESULTS: Included in
      the study were 122 males (63.2%) and 71 females (36.8%). Prevalence of NAFLD was
      82.9% (95% CI 77.6-88.2%). Prevalence was higher in males (p = 86.9%; 95% CI 80.9
      92.9%) than in females (p = 76.1%; 95% CI 66.1-86.0%). There were no age
      differences. A higher proportion of patients had mild (52.3%) or moderate (22.3%)
      NAFLD and in only 16 patients was NAFLD severe (8.3%). CONCLUSIONS: The observed
      prevalence is alarming because 8/10 subjects with MetS had NAFLD in any stage.
      Health-related measures oriented to decrease the incidence of the MetS will have
      a favorable impact on the occurrence of NAFLD.

PMID- 22644008
TI  - Treatment of arterial pseudoaneurysms with percutaneous ultrasound-guided
      thrombin injection.
AB  - BACKGROUND: The pseudoaneurysms or false aneurysms are one of the most common
      complications after arterial invasive manipulation. Different methods of
      treatment have been described, such as surgical repair, ultrasound-guided
      compression and endovascular procedures. Ultrasound-guided thrombin injection has
      shown efficacy, safety and  low cost, and, in some cases, the procedure is
      considered the treatment of choice. Preliminary results are presented. METHODS: 
      DESIGN: Case series. We studied adult patients with iatrogenic arterial
      pseudoaneurysms demonstrated clinically and corroborated with ultrasound. We
      describe the technique used for the management of the arterial pseudoaneurysms by
      ultrasound-guided thrombin application, as well as complications and follow-up.
      RESULTS: Twelve patients were included with a mean age of 63 years (SD 12.4), 33%
      were male and 67% female. Associated comorbid states were hypertension 83%, 50%
      diabetes, obesity 66%.  All pseudoaneurysms were located in the femoral artery
      (2:1 right/left ratio). The mean size of the pseudoaneurysm was 48.2 mm SD 11.9,
      (range of 30 to 65 mm) by 44.3 mm SD 9.3, (range 20 to 53 mm). The average neck
      diameter was 2.2 mm SD 0.54 (range of 1.5 to 3 mm). Eleven cases were
      unilobulated (87.5%), and one bilobulated (12.5%). All reported arterial
      integrity with complete occlusion after one thrombin application without
      recurrence and morbidity after 90 days of follow up. CONCLUSIONS: In our study we
      obtained a 100% of thrombosis without pseudoaneurysm recurrence or complications.
      However a longer follow-up time and more number of cases are required to confirm
      these results.

PMID- 22644009
TI  - Glycophosphopeptical as adjuvant treatment of diabetic foot injury: a pilot
      study.
AB  - BACKGROUND: Due to the complexity of the diabetic foot, its high frequency of
      amputations and accompanying immunosuppression, treatment is difficult. We tested
      the usefulness of glycophosphopetical immunoregulator as adjuvant therapy for
      diabetic foot injury. METHODS: We carried out a prospective double-blind
      randomized controlled study with 19 patients per group with diabetic foot injury
      III and IV (Wagner injury classification). The study group was treated orally
      with glycophosphopeptical (1 g/every 8 h for 4 weeks). Control group was treated
      with placebo. Both groups received conventional treatment: wound debridement,
      antibiotic therapy and metabolic control. Area and depth of injury was measured
      at the beginning of the study and after 2 months. Patients who were healed or
      showed improvement were quantified as well with serum levels of TNF-alpha,
      interferon-gamma and IL-1beta, 15 days after treatment initiation. RESULTS: The
      study group was comprised of 13 males and six females (mean age 61.6 +/- 14.9
      years) and the control group was comprised of five females and 14 males (mean age
      56.7 +/- 14.6 years). At the end of the study, the area and depth of the lesions
      were significantly lower in the study group (p <0.05). There were 13 amputations
      in the study group vs. 17 in the control group. In the group treated with
      glycophosphopeptical, there were 15 patient who were healed or improved and four
      failures vs. seven patients in the control group who were healed or improved and
      12 failures. There were only four failures in the study group vs. seven in the
      control group with 12 failures (p = 0.03). TNF-alpha was lower in the study group
      than in the control group (p <0.02). CONCLUSION: Glycophosphopeptical is useful
      as adjuvant therapy in diabetic foot injuries.

PMID- 22644010
TI  - Prevention of intestinal adhesions as a result of intraperitoneal mesh with the
      addition of hyaluronic acid/carboxymethylcellulose gel. Experimental model in
      rats.
AB  - BACKGROUND: Intraperitoneal meshes produce adhesions and intestinal fistula.
      Composite materials with an antiadherent barrier prevent that complication. There
      are no studies using gel products in intraperitoneal meshes to keep in contact
      with viscera. METHODS: Two groups of 20 rats each were used. Polypropylene mesh
      was placed intraperitoneally in both groups adding hyaluronic
      acid/carboxymethylcellulose gel to the mesh in the study group. At 28 days, rats
      were sacrificed and evaluated using the Diamond adhesions scale. RESULTS: There
      were 20 rats in the study group and 19 rats in the control group (one
      postoperative death). Control group all had adhesions: six (32%) >50% of the mesh
      surface. In the study group one rat (5%) showed no adhesions, and in 14 (70%)
      <25% of the mesh surface. Severity showed strong and cohesive adhesions in 11
      (58%) control group rats and thin, avascular adhesions in 11 (55%) study group
      rats. For density, in the study group there were two rats (10%) where adhesions
      were released spontaneously by separating the flap. There was mild to moderate
      traction in 16 (80%) study group rats and six (32%) control group rats.
      Adhesiolysis with scissors was used in the study group (5%) and in 13 (68%)
      control group rats (p <0.05). CONCLUSIONS: Hyaluronic acid/carboxymethylcellulose
      gel appears to be effective in reducing the percentage of adhesions to segments
      of intraperitoneal mesh implants.

PMID- 22644011
TI  - Evaluation of a surgical simulator as used by students with different experience
      levels.
AB  - BACKGROUND: Historically, the operating room has been the training setting for
      both surgeons and students. Nowadays, an alternative is represented by surgical
      simulators. In the same way a not-very-well-built mirror cannot reflect
      trustworthy images (distortion), a not well-built, calibrated or programmed
      simulator will be unable to reflect the training level of the operator. Our aim
      is to indirectly evaluate the Surgical SIM(r) simulator. METHODS: Twelve surgical
      residents were classified according to novices, intermediates and experts, and 15
      tasks were applied with three dimensions of evaluation in each using the Surgical
      SIM(r) simulator. Pearson's correlation test was used to establish validity.
      RESULTS: In general, from the three dimensions evaluated, results showed a
      statistically significant difference for time (p = 0.001), trajectory (p = 0.01)
      and errors (p = 0.001). CONCLUSIONS: Effectiveness of Surgical SIM(r) was
      indirectly demonstrated.

PMID- 22644012
TI  - Readability of education and consent forms in assisted reproduction procedures of
      the Latin American Network of Assisted Reproduction (RED).
AB  - BACKGROUND: Informed consent (IC) is the process where the patient receives
      information provided by the medical staff to understand key aspects of any
      intervention to be performed on the patient and for the patient to have the right
      to allow (or not) that such intervention takes place. To accomplish this
      objective, health care workers have two groups of tools: those that evaluate the
      capacity (and competence) of patients and those that facilitate the information
      and communication process. Among these are clinical interviewing skills,
      relationship help, emotional support (counseling) and written forms of IC. The IC
      process is difficult in assisted reproduction due to the quantity and complexity
      of information on human fertility, developmental biology, and technology
      applications. The Latin American Network of Assisted Reproduction has had eight
      "education and consent forms in assisted reproductive procedures" since 2001. We
      undertook this study to measure the readability of the formal language "education
      and consent forms in assisted reproduction procedures" proposed by LANAR with the
      Flesch index validated in Spanish. METHODS: Eight files were obtained in
      Microsoft Word format to use tools. The INFLESZ scale was used to assess the
      formal linguistics readability of each of the eight forms. CONCLUSIONS: The eight
      forms have a readability of "somewhat difficult," which corresponds to the
      INFLESZ scale for specialist press and popular science texts, making them
      difficult to understand for an average reader. Based on this, it should be
      proposed to amend formal readability.

PMID- 22644013
TI  - Plasma cell tumor of the clivus: report of two cases.
AB  - BACKGROUND: Plasma cell tumor only rarely affects the cranium and may be found as
      an isolated lesion or as a part of multiple myeloma. In this review we present
      the clinical and radiological characteristics and analyze the evolution of two
      cases of this tumor located at the skull base, specifically in the clivus and
      sellar region. We also present a brief review of the literature. CLINICAL CASES:
      Case #1: The patient was a 66-year-old female with a solitary plasmacytoma of the
      bone (the isolated form of plasma cell tumor) that was totally removed. Case #2:
      The patient was a 61-year-old male with the diffuse form of this disease who was
      submitted to subtotal removal. In both patients, adjuvant treatment based on
      radiotherapy and chemotherapy was proposed; however, only one patient (Case #2)
      accepted adjuvant treatment and had a very favorable result. Most clinical
      symptoms disappeared and the patient is currently alive and with a very good
      quality of life (>3-year follow-up). The other patient (Case #1), despite the
      presence of the localized form of the disease, died 3 months after diagnosis.
      CONCLUSION: Early diagnosis and removal of as much of the tumor as possible, but
      mainly the opportune indication of adjuvant treatment with radiotherapy and
      chemotherapy, are the keys to management of these cases.

PMID- 22644014
TI  - Unusual clinical presentation of astrocytoma in an adult.
AB  - BACKGROUND: Brainstem gliomas have a varied biological behavior based upon
      histopathological characteristics, localization and related diseases. The
      objective of this study is to present the clinical case of a grade II (diffuse)
      astrocytoma in an adult with an atypical clinical presentation including initial
      hiccup and dysphagia in a patient without evidence of clinical primary
      gastroenterology pathology. CLINICAL CASE: We describe the case of a 51-year-old
      male with a 4-year history of hiccup, oropharyngeal dysphagia and neurological
      clinical elements of tongue fasciculations, quadriparesis, generalized
      hyperreflexia due to astrocytoma with atypical localization in the floor of the
      fourth ventricle and histopathological diagnosis of low-grade diffuse glioma.
      CONCLUSIONS: Hiccup is a nonspecific symptom infrequently associated with
      neurological disorders. Adequate semiology of oropharyngeal dysphagia would help
      us to identify neurological entities such as in the case presented here.
      Additionally, with signs of upper and lower motor neuron we should suspect the
      possibility of central nervous system abnormalities of functional and organic
      etiology. Computed axial tomography and magnetic resonance imaging studies are
      important elements for diagnosis.

PMID- 22644015
TI  - Intracardiac malignant fibrous histiocytoma. A case report.
AB  - BACKGROUND: Primary cardiac tumors are rare forms of cardiac disease. The
      reported incidence varies between 0.002 and 0.3%; 25% of these tumors are
      malignant, usually a variant of sarcoma. Malignant fibrous histiocytoma
      constitutes <3% of primary cardiac tumors. CLINICAL CASE: We review the case of a
      53-year-old female who presented with congestive heart failure and pleural
      effusion. Transthoracic echocardiography and chest computed tomography revealed
      cardiac tumor involving the left atrium. Tumor was excised surgically and
      histologically proven to be a malignant fibrous histiocytoma, primarily confined
      to the heart. During the immediate postoperative evolution, the patient presented
      left pleural effusion for 2 weeks. The patient was referred to Oncology Service
      for complementary treatment. CONCLUSION: Malignant fibrous histiocytoma is a rare
      tumor and, in this case, prognosis is reserved.

PMID- 22644016
TI  - [Littre hernia: an unusual cause of intestinal obstruction.
AB  - BACKGROUND: Littre's hernia is the presence of a Meckel diverticulum within an
      orifice in the abdominal wall. There are few cases published in the literature
      and its frequency is not well described. CLINICAL CASE: We present the case of a
      74-year-old patient who arrived at the emergency service with clinical signs of
      intestinal obstruction caused by an incarcerated right inguinal hernia. Emergency
      surgery was performed using a preperitoneal approach. Within the hernia, 5 cm of
      small bowel containing a Meckel diverticulum was found. Therefore, we decided to
      extirpate the diverticulum and repair the hernia placing a polypropylene mesh.
      CONCLUSIONS: Meckel diverticulum is the persistence of the omphalomesenteric
      duct. It is usually asymptomatic, producing bleeding, infection or intestinal
      obstruction as the main symptoms.

PMID- 22644017
TI  - Giant Spiegelian hernia and abdominal trauma: cause or coincidence?
AB  - BACKGROUND: Spiegelian hernia is an uncommon entity and occurs as a result of a
      defect in the linea semilunaris located in the lateroventral abdominal wall.
      CLINICAL CASE: We report the case of a 44-year-old female with a history of
      progressive abdominal swelling. Clinical history included a previous blunt trauma
      to the abdomen. A Spiegelian hernia with a large aponeurotic defect (7 * 12 cm)
      and sac (15 * 15 cm) was diagnosed. A literature review of similar topics was
      performed. CONCLUSION: Weakness presented in the linea semilunaris in Spiegelian
      hernia may be caused either spontaneously or as a consequence of factors that
      increase intra-abdominal pressure. Otherwise, it is important to unify the terms
      related to the size of this entity in order to establish a correct
      classification.

PMID- 22644018
TI  - Numerical-experimental study of internal fixation system "Dufoo" for vertebral
      fractures.
AB  - BACKGROUND: We describe a numerical experimental study of the stress generated by
      the internal fixation system "Dufoo" used in the treatment of vertebral fractures
      with the purpose of validating the numerical model of human lumbar vertebrae
      under the main physiological loads that the human body is exposed to in this
      area. The objective is to model and numerically simulate the elements of the
      musculoskeletal system to collect the stresses generated and other parameters
      that are difficult to measure experimentally in the thoracic lumbar vertebrae.
      METHODS: We used an internal fixator "Dufoo" and vertebrae L2-L3-L4 specimens
      from pig and human. The system uses a total L3 corpectomy. The fixator acts as a
      mechanical bridge implant from L2 to L4. Numerical analysis was performed using
      the finite element method (FEM). For the experimental study, reflective
      photoelasticity and extensometry were used. RESULTS: Torsion and combined loads
      generate the main displacements and stresses in the study system, determining
      that the internal fixation carries out part of the function of the damaged organ
      structure when absorbing the stresses presented by applied loads. CONCLUSIONS:
      Numerical analysis allows great freedom in the management of the variables
      involved in the developed models using radiological images. Geometric models are
      obtained and are entered into FEM programs that allow testing using parameters
      that, under actual conditions, may not be easily carried out, allowing to
      comprehensively determine the biomechanical behavior of the coupled system of
      study.

PMID- 22644019
TI  - The medical education and its impact on public health. Perspectives and
      challenges.
AB  - BACKGROUND: This paper presents an analysis of the relevance of the formation of
      human resources trained in health sciences as an essential strategy for
      sustainability projects applied to health schemes. A solid linkage is required
      between training and application aspects through the transfer of knowledge in
      concrete actions. DISCUSSION: A series of actions aimed to improve the quality
      and coverage in health services has been proposed. However, the treatment given
      to education and training in human resources has not been in the same proportion.
      As a consequence, the formation of qualified human resources represents one of
      the fundamental axes to perform these actions in health fields. CONCLUSIONS:
      Training of human resources for health provided by educational institutions must
      not be separate from global decisions in health fields. Evidence shows that the
      higher density, quality and appropriate distribution of health workforce, the
      greater the impact on public health in an efficient manner. This rubric must be
      considered as a priority, achieving the training of professionals with leadership
      and with the ability of transforming their environment before the predictions
      about potential collapses in health systems are presented as an emerging
      challenge.

PMID- 22644020
TI  - Efficacy of LFF571 in a hamster model of Clostridium difficile infection.
AB  - LFF571 is a novel semisynthetic thiopeptide antibiotic with potent activity
      against a variety of Gram-positive pathogens, including Clostridium difficile. In
      vivo efficacy of LFF571 was compared to vancomycin in a hamster model of C.
      difficile infection (CDI). Infection was induced in Golden Syrian hamsters using
      a toxigenic strain of C. difficile. Treatment started 24 h postinfection and
      consisted of saline, vancomycin, or LFF571. Cox regression was used to analyze
      survival data from a cohort of animals evaluated across seven serial experimental
      groups treated with vancomycin at 20 mg/kg, LFF571 at 5 mg/kg, or vehicle alone.
      Survival was right censored; animals were not observed beyond day 21. At death or
      end of study, cecal contents were tested for C. difficile toxins A and B. In
      summary, the data showed that 5 mg/kg LFF571 decreased the risk of death by 79%
      (P < 0.0001) and 69% (P = 0.0022) compared with saline and 20 mg/kg vancomycin,
      respectively. Further analysis of the pooled data indicated that the survival
      benefit of LFF571 treatment at 5 mg/kg compared to vancomycin at 20 mg/kg was due
      primarily to a decrease in the risk of recurrence after end of treatment. Animals
      successfully treated with LFF571 or vancomycin had no detectable C. difficile
      toxin. Overall, LFF571 was more efficacious at the end of the study, at a lower
      dose, and with fewer recurrences, than vancomycin in the hamster model of CDI.
      LFF571 is being assessed in humans for safety and efficacy in the treatment of C.
      difficile infections.

PMID- 22644021
TI  - Adjunctive daptomycin attenuates brain damage and hearing loss more efficiently
      than rifampin in infant rat pneumococcal meningitis.
AB  - Exacerbation of cerebrospinal fluid (CSF) inflammation in response to
      bacteriolysis by beta-lactam antibiotics contributes to brain damage and
      neurological sequelae in bacterial meningitis. Daptomycin, a nonlytic antibiotic
      acting on Gram-positive bacteria, lessens inflammation and brain injury compared
      to ceftriaxone. With a view to a clinical application for pediatric bacterial
      meningitis, we investigated the effect of combining daptomycin or rifampin with
      ceftriaxone in an infant rat pneumococcal meningitis model. Eleven-day-old Wistar
      rats with pneumococcal meningitis were randomized to treatment starting at 18 h
      after infection with (i) ceftriaxone (100 mg/kg of body weight, subcutaneously
      [s.c.], twice a day [b.i.d.]), (ii) daptomycin (10 mg/kg, s.c., daily) followed
      15 min later by ceftriaxone, or (iii) rifampin (20 mg/kg, intraperitoneally
      [i.p.], b.i.d.) followed 15 min later by ceftriaxone. CSF was sampled at 6 and 22
      h after the initiation of therapy and was assessed for concentrations of defined
      chemokines and cytokines. Brain damage was quantified by histomorphometry at 40 h
      after infection and hearing loss was assessed at 3 weeks after infection.
      Daptomycin plus ceftriaxone versus ceftriaxone significantly (P < 0.04) lowered
      CSF concentrations of monocyte chemoattractant protein 1 (MCP-1), MIP-1alpha, and
      interleukin 6 (IL-6) at 6 h and MIP-1alpha, IL-6, and IL-10 at 22 h after
      initiation of therapy, led to significantly (P < 0.01) less apoptosis, and
      significantly (P < 0.01) improved hearing capacity. While rifampin plus
      ceftriaxone versus ceftriaxone also led to lower CSF inflammation (P < 0.02 for
      IL-6 at 6 h), it had no significant effect on apoptosis and hearing capacity.
      Adjuvant daptomycin could therefore offer added benefits for the treatment of
      pediatric pneumococcal meningitis.

PMID- 22644022
TI  - Identification of disubstituted sulfonamide compounds as specific inhibitors of
      hepatitis B virus covalently closed circular DNA formation.
AB  - Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays a central
      role in viral infection and persistence and is the basis for viral rebound after
      the cessation of therapy, as well as the elusiveness of a cure even after
      extended treatment. Therefore, there is an urgent need for the development of
      novel therapeutic agents that directly target cccDNA formation and maintenance.
      By employing an innovative cell-based cccDNA assay in which secreted HBV e
      antigen is a cccDNA-dependent surrogate, we screened an in-house small-molecule
      library consisting of 85,000 drug-like compounds. Two structurally related
      disubstituted sulfonamides (DSS), termed CCC-0975 and CCC-0346, emerged and were
      confirmed as inhibitors of cccDNA production, with low micromolar 50% effective
      concentrations (EC(50)s) in cell culture. Further mechanistic studies
      demonstrated that DSS compound treatment neither directly inhibited HBV DNA
      replication in cell culture nor reduced viral polymerase activity in the in vitro
      endogenous polymerase assay but synchronously reduced the levels of HBV cccDNA
      and its putative precursor, deproteinized relaxed circular DNA (DP-rcDNA).
      However, DSS compounds did not promote the intracellular decay of HBV DP-rcDNA
      and cccDNA, suggesting that the compounds interfere primarily with rcDNA
      conversion into cccDNA. In addition, we demonstrated that CCC-0975 was able to
      reduce cccDNA biosynthesis in duck HBV-infected primary duck hepatocytes. This is
      the first attempt, to our knowledge, to identify small molecules that target
      cccDNA formation, and DSS compounds thus potentially serve as proof-of-concept
      drug candidates for development into therapeutics to eliminate cccDNA from
      chronic HBV infection.

PMID- 22644023
TI  - Mechanism of action of and mechanism of reduced susceptibility to the novel anti
      Clostridium difficile compound LFF571.
AB  - LFF571 is a novel semisynthetic thiopeptide and potent inhibitor of Gram-positive
      bacteria. We report that the antibacterial activity of LFF571 against Clostridium
      difficile is due to inhibition of translation. Single-step mutants of C.
      difficile with reduced susceptibility to LFF571 were selected at frequencies of
      <4.5 * 10(-11) to 1.2 * 10(-9). Sequencing revealed a G260E substitution in the
      thiopeptide-binding pocket of elongation factor Tu. Importantly, this mutation
      did not confer cross-resistance to clinically used antimicrobials. These results
      support the development of LFF571 as a treatment for C. difficile infection.

PMID- 22644024
TI  - A model for evaluating topical antimicrobial efficacy against methicillin
      resistant Staphylococcus aureus biofilms in superficial murine wounds.
AB  - A wound biofilm model was created by adapting a superficial infection model.
      Partial-thickness murine wounds were inoculated with methicillin-resistant
      Staphylococcus aureus (MRSA). Dense biofilm communities developed at the wound
      surface after 24 h as demonstrated by microscopy and quantitative microbiology.
      Common topical antimicrobial agents had reduced efficacy when treatment was
      initiated 24 h after inoculation compared to 4 h after inoculation. This model
      provides a rapid in vivo test for new agents to treat wound biofilm infections.

PMID- 22644025
TI  - Role of innate immune receptors in paradoxical caspofungin activity in vivo in
      preclinical aspergillosis.
AB  - This study investigated the possible mechanisms underlying the paradoxical
      caspofungin activity in vivo in preclinical aspergillosis. We evaluated the
      activity of escalating doses of caspofungin in vivo in different preclinical
      models of invasive aspergillosis, including mice deficient for selected innate
      immune receptors. The therapeutic efficacy of caspofungin in experimental
      invasive aspergillosis was strictly dose dependent, being observed at doses of
      0.1 and 1 mg/kg of body weight depending on the experimental models. Paradoxical
      increase in pulmonary fungal burden as well as inflammatory pathology was
      observed at the highest dose of caspofungin (5 mg/kg), occurred independently of
      the so-called Eagle effect and susceptibility to caspofungin in vitro, and was
      contingent upon the presence of TLR2, Dectin-1, and TLR9. Increased expression of
      Dectin-1 and TLR9 were observed upon exposure to caspofungin in vitro and in
      vivo. Together, these findings suggest that the net activity of caspofungin in
      vivo is orchestrated by the activation, directly or indirectly, of multiple
      innate immune receptors.

PMID- 22644026
TI  - Effect of rifampin and rifabutin on the pharmacokinetics of lersivirine and
      effect of lersivirine on the pharmacokinetics of rifabutin and 25-O-desacetyl
      rifabutin in healthy subjects.
AB  - Lersivirine is a nonnucleoside reverse transcriptase inhibitor (NNRTI) with a
      unique resistance profile exhibiting potent antiviral activity against wild-type
      HIV and several clinically relevant NNRTI-resistant strains. Lersivirine, a weak
      inducer of the cytochrome P450 (CYP) enzyme CYP3A4, is metabolized by CYP3A4 and
      UDP glucuronosyltransferase 2B7 (UGT2B7). Two open, randomized, two-way (study 1;
      study A5271008) or three-way (study 2; study A5271043) crossover phase I studies
      were carried out under steady-state conditions in healthy subjects. Study 1 (n =
      17) investigated the effect of oral rifampin on the pharmacokinetics (PKs) of
      lersivirine. Study 2 (n = 18) investigated the effect of oral rifabutin on the
      PKs of lersivirine and the effect of lersivirine on the PKs of rifabutin and its
      active metabolite, 25-O-desacetyl-rifabutin. Coadministration with rifampin
      decreased the profile of the lersivirine area under the plasma concentration-time
      curve from time zero to 24 h postdose (AUC(24)), maximum plasma concentration
      (C(max)), and plasma concentration observed at 24 h postdose (C(24)) by 85% (90%
      confidence interval [CI], 83, 87), 83% (90% CI, 79, 85), and 92% (90% CI, 89,
      94), respectively, versus the values for lersivirine alone. Coadministration with
      rifabutin decreased the lersivirine AUC(24), C(max), and C(24) by 34% (90% CI,
      29, 39), 25% (90% CI, 16, 33), and 58% (90% CI, 52, 64), respectively, compared
      with the values for lersivirine alone. Neither the rifabutin concentration
      profile nor overall exposure was affected following coadministration with
      lersivirine. Lersivirine and rifabutin reduced the 25-O-desacetyl-rifabutin
      AUC(24) by 27% (90% CI, 21, 32) and C(max) by 27% (90% CI, 19, 34). Lersivirine
      should not be coadministered with rifampin, which is a potent inducer of CYP3A4,
      UGT2B7, and P-glycoprotein activity and thus substantially lowers lersivirine
      exposure. No dose adjustment of rifabutin is necessary in the presence of
      lersivirine; an upward dose adjustment of lersivirine may be warranted when it is
      coadministered with rifabutin.

PMID- 22644027
TI  - Anidulafungin for Candida glabrata infective endocarditis.

PMID- 22644028
TI  - Characterization of RarA, a novel AraC family multidrug resistance regulator in
      Klebsiella pneumoniae.
AB  - Transcriptional regulators, such as SoxS, RamA, MarA, and Rob, which upregulate
      the AcrAB efflux pump, have been shown to be associated with multidrug resistance
      in clinically relevant Gram-negative bacteria. In addition to the multidrug
      resistance phenotype, these regulators have also been shown to play a role in the
      cellular metabolism and possibly the virulence potential of microbial cells. As
      such, the increased expression of these proteins is likely to cause pleiotropic
      phenotypes. Klebsiella pneumoniae is a major nosocomial pathogen which can
      express the SoxS, MarA, Rob, and RamA proteins, and the accompanying paper shows
      that the increased transcription of ramA is associated with tigecycline
      resistance (M. Veleba and T. Schneiders, Antimicrob. Agents Chemother. 56:4466
      4467, 2012). Bioinformatic analyses of the available Klebsiella genome sequences
      show that an additional AraC-type regulator is encoded chromosomally. In this
      work, we characterize this novel AraC-type regulator, hereby called RarA
      (Regulator of antibiotic resistance A), which is encoded in K. pneumoniae,
      Enterobacter sp. 638, Serratia proteamaculans 568, and Enterobacter cloacae. We
      show that the overexpression of rarA results in a multidrug resistance phenotype
      which requires a functional AcrAB efflux pump but is independent of the other
      AraC regulators. Quantitative real-time PCR experiments show that rarA (MGH 78578
      KPN_02968) and its neighboring efflux pump operon oqxAB (KPN_02969_02970) are
      consistently upregulated in clinical isolates collected from various geographical
      locations (Chile, Turkey, and Germany). Our results suggest that rarA
      overexpression upregulates the oqxAB efflux pump. Additionally, it appears that
      oqxR, encoding a GntR-type regulator adjacent to the oqxAB operon, is able to
      downregulate the expression of the oqxAB efflux pump, where OqxR complementation
      resulted in reductions to olaquindox MICs.

PMID- 22644029
TI  - Resistance to a novel antichlamydial compound is mediated through mutations in
      Chlamydia trachomatis secY.
AB  - A novel and quantitative high-throughput screening approach was explored as a
      tool for the identification of novel compounds that inhibit chlamydial growth in
      mammalian cells. The assay is based on accumulation of a fluorescent marker by
      intracellular chlamydiae. Its utility was demonstrated by screening 42,000
      chemically defined compounds against Chlamydia caviae GPIC. This analysis led to
      the identification of 40 primary-hit compounds. Five of these compounds were
      nontoxic to host cells and had similar activities against both C. caviae GPIC and
      Chlamydia trachomatis. The inhibitory activity of one of the compounds, (3
      methoxyphenyl)-(4,4,7-trimethyl-4,5-dihydro-1H-[1,2]dithiolo[3,4-C]quinolin-1
      ylidene)amine (MDQA), was chlamydia specific and was selected for further study.
      Selection for resistance to MDQA led to the generation of three independent
      resistant clones of C. trachomatis. Amino acid changes in SecY, a protein
      involved in Sec-dependent secretion in Gram-negative bacteria, were associated
      with the resistance phenotype. The amino acids changed in each of the resistant
      mutants are located in the predicted central channel of a SecY crystal structure,
      based on the known structure of Thermus thermophilus SecY. These experiments
      model a process that can be used for the discovery of antichlamydial, anti
      intracellular, or antibacterial compounds and has led to the identification of
      compounds that may have utility in both antibiotic discovery and furthering our
      understanding of chlamydial biology.

PMID- 22644030
TI  - Clinical and antimicrobial susceptibility data of 140 Streptococcus
      pseudopneumoniae isolates in France.
AB  - We report retrospective analysis of the clinical and antimicrobial susceptibility
      data of 140 Streptococcus pseudopneumoniae isolates. Strains were isolated mostly
      from respiratory tract samples from patients with underlying diseases. In the
      case of infection, pneumonia, mainly aspiration pneumonia, was the most frequent
      (27.1% of the patients). We documented high rates of decreased susceptibilities
      and resistance to erythromycin and tetracycline (57% and 43% of the isolates,
      respectively), as well as reduced susceptibility to penicillin in 21% of the
      isolates.

PMID- 22644031
TI  - In vivo emergence of tigecycline resistance in multidrug-resistant Klebsiella
      pneumoniae and Escherichia coli.
AB  - Although resistance to tigecycline has been reported in surveillance studies,
      very few reports have described the emergence of resistance in vivo. We report
      two cases of patients with infections due to SHV-12-producing Klebsiella
      pneumoniae and K. pneumoniae carbapenemase-3 (KPC-3)-producing Escherichia coli,
      which developed tigecycline resistance in vivo after treatment. The reported
      limited experience underlines the risk of occurrence of a tigecycline MIC
      increase under treatment pressure.

PMID- 22644032
TI  - Mutations in 23S rRNA confer resistance against azithromycin in Pseudomonas
      aeruginosa.
AB  - The emergence of antibiotic-resistant Pseudomonas aeruginosa is an important
      concern in the treatment of long-term airway infections in cystic fibrosis
      patients. In this study, we report the occurrence of azithromycin resistance
      among clinical P. aeruginosa DK2 isolates. We demonstrate that resistance is
      associated with specific mutations (A2058G, A2059G, and C2611T in Escherichia
      coli numbering) in domain V of 23S rRNA and that introduction of A2058G and
      C2611T into strain PAO1 results in azithromycin resistance.

PMID- 22644033
TI  - High-dose daptomycin plus fosfomycin is safe and effective in treating
      methicillin-susceptible and methicillin-resistant Staphylococcus aureus
      endocarditis.
AB  - We describe 3 patients with left-sided staphylococcal endocarditis (1 with
      methicillin-susceptible Staphylococcus aureus [MSSA] prosthetic aortic valve
      endocarditis and 2 with methicillin-resistant S. aureus [MRSA] native-valve
      endocarditis) who were successfully treated with high-dose intravenous daptomycin
      (10 mg/kg/day) plus fosfomycin (2 g every 6 h) for 6 weeks. This combination was
      tested in vitro against 7 MSSA, 5 MRSA, and 2 intermediately glycopeptide
      resistant S. aureus isolates and proved to be synergistic against 11 (79%)
      strains and bactericidal against 8 (57%) strains. This combination deserves
      further clinical study.

PMID- 22644034
TI  - Tigecycline resistance can occur independently of the ramA gene in Klebsiella
      pneumoniae.
AB  - Tigecycline resistance in Klebsiella pneumoniae results from ramA upregulation
      that causes the overexpression of the efflux pump, AcrAB-TolC. Tigecycline
      mutants, derived from Ecl8DeltaramA, can exhibit a multidrug resistance phenotype
      due to increased transcription of the marA, rarA, acrAB, and oqxAB genes. These
      findings support the idea that tigecycline or multidrug resistance in K.
      pneumoniae, first, is not solely dependent on the ramA gene, and second, can
      arise via alternative regulatory pathways in K. pneumoniae.

PMID- 22644035
TI  - Mutations in HIV-1 gag and pol compensate for the loss of viral fitness caused by
      a highly mutated protease.
AB  - During the last few decades, the treatment of HIV-infected patients by highly
      active antiretroviral therapy, including protease inhibitors (PIs), has become
      standard. Here, we present results of analysis of a patient-derived,
      multiresistant HIV-1 CRF02_AG recombinant strain with a highly mutated protease
      (PR) coding sequence, where up to 19 coding mutations have accumulated in the PR.
      The results of biochemical analysis in vitro showed that the patient-derived PR
      is highly resistant to most of the currently used PIs and that it also exhibits
      very poor catalytic activity. Determination of the crystal structure revealed
      prominent changes in the flap elbow region and S1/S1' active site subsites. While
      viral loads in the patient were found to be high, the insertion of the patient
      derived PR into a HIV-1 subtype B backbone resulted in reduction of infectivity
      by 3 orders of magnitude. Fitness compensation was not achieved by elevated
      polymerase (Pol) expression, but the introduction of patient-derived gag and pol
      sequences in a CRF02_AG backbone rescued viral infectivity to near wild-type (wt)
      levels. The mutations that accumulated in the vicinity of the processing sites
      spanning the p2/NC, NC/p1, and p6pol/PR proteins lead to much more efficient
      hydrolysis of corresponding peptides by patient-derived PR in comparison to the
      wt enzyme. This indicates a very efficient coevolution of enzyme and substrate
      maintaining high viral loads in vivo under constant drug pressure.

PMID- 22644036
TI  - Analysis of differential plaque depositions in the brains of Tg2576 and Tg
      APPswe/PS1dE9 transgenic mouse models of Alzheimer disease.
AB  - Adequate assessment of plaque deposition levels in the brain of mouse models of
      Alzheimer disease (AD) is required in many core issues of studies on AD,
      including studies on the mechanisms underlying plaque pathogenesis,
      identification of cellular factors modifying plaque pathology, and developments
      of anti-AD drugs. The present study was undertaken to quantitatively evaluate
      plaque deposition patterns in the brains of the two popular AD models, Tg2576 and
      Tg-APPswe/ PS1dE9 mice. Coronally-cut brain sections of Tg2576 and Tg
      APPswe/PS1dE9 mice were prepared and plaque depositions were visualized by
      staining with anti- amyloid beta peptides antibody. Microscopic images of plaque
      depositions in the prefrontal cortex, parietal cortex, piriform cortex and
      hippocampus were obtained and the number of plaques in each region was determined
      by a computer-aided image analysis method. A series of optical images
      representing a gradual increase of plaque deposition levels were selected in the
      four different brain regions and were assigned in each with a numerical grade of
      1-6, where +1 was lowest and +6, highest, so that plaques per unit in mm(2)
      increased "sigmoidally" over the grading scales. Analyzing plaque depositions
      using the photographic plaque reference panels and a computer-aid image analysis
      method, it was demonstrated that the brains of Tg2576 mice started to accumulate
      predominantly small plaques, while the brains of Tg-APPswe/PS1dE9 mice deposited
      relatively large plaques.

PMID- 22644042
TI  - Preparation and characterization of DNA aptamer based spin column for enrichment
      and separation of histones.
AB  - Core histones play a critical role in the regulation of chromatin-templated
      biological process. Here we have developed a novel approach to enrich histone
      proteins based on the recognition of a specific aptamer. The method shows good
      selectivity toward histone proteins and is able to extract histones directly from
      complex whole cell lysates.

PMID- 22644043
TI  - Bioaccumulation and elimination of waterborne mercury in the midge larvae,
      Chironomus riparius Meigen (Diptera: Chironomidae).
AB  - Here, mercury kinetics and behavioural effects in the midge larvae under a water
      only exposure were assessed. Uptake and elimination of waterborne mercury were
      described by using a one-compartment kinetic model. Results show that midges were
      able to readily accumulate the heavy metal (BCF = 450), presenting a fast uptake,
      up to 13.1 MUg Hg g of animal(-1) at the end of the exposure period. Elimination
      was slow, with c.a. 39 % of the mercury in larvae being depurated after 48 h in
      clean medium. Behaviour did not present differences upon exposure or elimination,
      but a trend to increase ventilation was noticed during the exposure period.

PMID- 22644044
TI  - Temporal variation of metals in water, sediment and tissues of the European chup
      (Squalius cephalus L.).
AB  - The aim of this study was to analyze seasonal variation of levels of Chromium
      (Cr), Manganese (Mn), Nickel (Ni), Copper (Cu), Zinc (Zn), Cadmium (Cd) and Lead
      (Pb) in water, sediment and tissues of Squalius cephalus (L., 1758) taken from
      five different stations chosen at Yamula Dam Lake (Kayseri, Turkey).
      Concentrations of metals were generally sorted as water < tissue < sediment. The
      highest concentration of metals in water was observed in the samples taken in the
      summer (Mn, 1.04 +/- 0.15 mg L(-1); Ni, 0.42 +/- 0.12 mg L(-1); Cu, 1.25 +/- 0.88
      mg L(-1); Zn, 3.61 +/- 1.53 mg L(-1); Pb, 0.58 +/- 0.09 mg L(-1)). While the
      highest Zn (24.85 +/- 21.82 MUg g(-1)) and Pb (10.89 +/- 4.2 MUg g(-1))
      concentrations in sediment were observed in the winter samples, the highest Mn
      concentration (167.2 +/- 99.37 MUg g(-1)) was observed in the summer. Cd
      pollution was determined in sediment according to international criteria. The
      highest metal concentration in tissues was generally observed in the liver and
      the other tissues; following liver were gills and muscles. In liver tissues,
      while the highest accumulation of Zn (110.34 +/- 13.1) and Mn (22.5 +/- 14.85 MUg
      g(-1)), which are essential for the body, were observed in the winter, Pb (22.58
      +/- 7.83 MUg g(-1)) and Cd (11.77 +/- 7.83 MUg g(-1)), which are toxic, were
      found to be higher in the summer. Also, concentrations of Mn, Cd and Pb in muscle
      tissues were found to be above the limits permitted.

PMID- 22644045
TI  - Acute toxicity of sodium metabisulphite in larvae and post-larvae of the land
      crab, Cardisoma guanhumi.
AB  - Sodium metabisulphite (SMB) is used in marine shrimp aquaculture to prevent the
      occurrence of black spot. The release SMB into the estuarine environment from
      shrimp farm pond effluents has been reported. This study evaluated the
      susceptibility of larvae and post-larvae of land crab, Cardisoma guanhumi to this
      salt. A decrease in dissolved oxygen and pH occurred with increasing
      concentration of SMB and exposure time. LC(50) values after 48 h of exposure were
      34 +/- 1.1 mg/L, 31.1 +/- 1.9 mg/L, and 30.6 +/- 0.5 mg/L for I zoea larvae,
      megalopa larvae and stage I juveniles, respectively.

PMID- 22644046
TI  - Isolation and characterization of dendritic cells and macrophages from the mouse
      intestine.
AB  - Within the intestine reside unique populations of innate and adaptive immune
      cells that are involved in promoting tolerance towards commensal flora and food
      antigens while concomitantly remaining poised to mount inflammatory responses
      toward invasive pathogens. Antigen presenting cells, particularly DCs and
      macrophages, play critical roles in maintaining intestinal immune homeostasis via
      their ability to sense and appropriately respond to the microbiota. Efficient
      isolation of intestinal DCs and macrophages is a critical step in characterizing
      the phenotype and function of these cells. While many effective methods of
      isolating intestinal immune cells, including DCs and macrophages, have been
      described, many rely upon long digestions times that may negatively influence
      cell surface antigen expression, cell viability, and/or cell yield. Here, we
      detail a methodology for the rapid isolation of large numbers of viable,
      intestinal DCs and macrophages. Phenotypic characterization of intestinal DCs and
      macrophages is carried out by directly staining isolated intestinal cells with
      specific fluorescence-labeled monoclonal antibodies for multi-color flow
      cytometric analysis. Furthermore, highly pure DC and macrophage populations are
      isolated for functional studies utilizing CD11c and CD11b magnetic-activated cell
      sorting beads followed by cell sorting.

PMID- 22644048
TI  - Post-mortem ecosystem engineering by oysters creates habitat for a rare marsh
      plant.
AB  - Oysters are ecosystem engineers in marine ecosystems, but the functions of oyster
      shell deposits in intertidal salt marshes are not well understood. The annual
      plant Suaeda linearis is associated with oyster shell deposits in Georgia salt
      marshes. We hypothesized that oyster shell deposits promoted the distribution of
      Suaeda linearis by engineering soil conditions unfavorable to dominant salt marsh
      plants of the region (the shrub Borrichia frutescens, the rush Juncus
      roemerianus, and the grass Spartina alterniflora). We tested this hypothesis
      using common garden pot experiments and field transplant experiments. Suaeda
      linearis thrived in Borrichia frutescens stands in the absence of neighbors, but
      was suppressed by Borrichia frutescens in the with-neighbor treatment, suggesting
      that Suaeda linearis was excluded from Borrichia frutescens stands by
      interspecific competition. Suaeda linearis plants all died in Juncus roemerianus
      and Spartina alterniflora stands, regardless of neighbor treatments, indicating
      that Suaeda linearis is excluded from these habitats by physical stress (likely
      water-logging). In contrast, Borrichia frutescens, Juncus roemerianus, and
      Spartina alterniflora all performed poorly in Suaeda linearis stands regardless
      of neighbor treatments, probably due to physical stresses such as low soil water
      content and low organic matter content. Thus, oyster shell deposits play an
      important ecosystem engineering role in influencing salt marsh plant communities
      by providing a unique niche for Suaeda linearis, which otherwise would be rare or
      absent in salt marshes in the southeastern US. Since the success of Suaeda
      linearis is linked to the success of oysters, efforts to protect and restore
      oyster reefs may also benefit salt marsh plant communities.

PMID- 22644047
TI  - Effects of local biotic neighbors and habitat heterogeneity on tree and shrub
      seedling survival in an old-growth temperate forest.
AB  - Seedling dynamics play a crucial role in determining species distributions and
      coexistence. Exploring causes of variation in seedling dynamics can therefore
      provide key insights into the factors affecting these phenomena. We examined the
      relative importance of biotic neighborhood processes and habitat heterogeneity
      using survival data for 5,827 seedlings in 39 tree and shrub species over 2 years
      from an old-growth temperate forest in northeastern China. We found significant
      negative density-dependence effects on survival of tree seedlings, and limited
      effects of habitat heterogeneity (edaphic and topographic variables) on survival
      of shrub seedlings. The importance of negative density dependence on young tree
      seedling survival was replaced by habitat in tree seedlings >= 4 years old. As
      expected, negative density dependence was more apparent in gravity-dispersed
      species compared to wind-dispersed and animal-dispersed species. Moreover, we
      found that a community compensatory trend existed for trees. Therefore, although
      negative density dependence was not as pervasive as in other forest communities,
      it is an important mechanism for the maintenance of community diversity in this
      temperate forest. We conclude that both negative density dependence and habitat
      heterogeneity drive seedling survival, but their relative importance varies with
      seedling age classes and species traits.

PMID- 22644049
TI  - Lifetime offspring production in relation to breeding lifespan, attractiveness,
      and mating status in male collared flycatchers.
AB  - As a comprehensive fitness parameter, lifetime reproductive success (LRS) is
      influenced by many different environmental and genetic factors, among which
      longevity is one of the most important. These factors can be reflected in
      secondary sexual characters, which may affect the life histories of individuals
      via social relations with conspecifics. Facultative polygyny in birds is another
      conspicuous reproductive trait that potentially increases male reproductive
      success, but lifetime success data in relation to polygyny are scarce. Here, we
      used 17 years of breeding data to quantify the LRS of male collared flycatchers
      (Ficedula albicollis) on the basis of lifetime recruitment of offspring. Breeding
      lifespan showed a positive relationship with LRS, and it was also significantly
      associated with mean recruitment of offspring per breeding year. Body size and
      sexually selected forehead patch size did not predict the number of recruits.
      Polygyny was positively associated with LRS, but when we corrected for lifespan,
      this relationship disappeared. Our results demonstrate that the relationship
      between longevity and LRS is not explained by the higher number of reproductive
      attempts when living longer, and question the adaptive value of polygyny in this
      population. The lack of association between forehead patch size and recruitment
      suggests that forehead patch is a poor indicator of phenotypic quality in our
      birds.

PMID- 22644050
TI  - Agricultural intensification and cereal aphid-parasitoid-hyperparasitoid food
      webs: network complexity, temporal variability and parasitism rates.
AB  - Agricultural intensification (AI) is currently a major driver of biodiversity
      loss and related ecosystem functioning decline. However, spatio-temporal changes
      in community structure induced by AI, and their relation to ecosystem
      functioning, remain largely unexplored. Here, we analysed 16 quantitative cereal
      aphid-parasitoid and parasitoid-hyperparasitoid food webs, replicated four times
      during the season, under contrasting AI regimes (organic farming in complex
      landscapes vs. conventional farming in simple landscapes). High AI increased food
      web complexity but also temporal variability in aphid-parasitoid food webs and in
      the dominant parasitoid species identity. Enhanced complexity and variability
      appeared to be controlled bottom-up by changes in aphid dominance structure and
      evenness. Contrary to the common expectations of positive biodiversity-ecosystem
      functioning relationships, community complexity (food-web complexity, species
      richness and evenness) was negatively related to primary parasitism rates.
      However, this relationship was positive for secondary parasitoids. Despite
      differences in community structures among different trophic levels, ecosystem
      services (parasitism rates) and disservices (aphid abundances and hyperparasitism
      rates) were always higher in fields with low AI. Hence, community structure and
      ecosystem functioning appear to be differently influenced by AI, and change
      differently over time and among trophic levels. In conclusion, intensified
      agriculture can support diverse albeit highly variable parasitoid-host
      communities, but ecosystem functioning might not be easy to predict from observed
      changes in community structure and composition.

PMID- 22644051
TI  - Winter predation by insectivorous birds and consequences for arthropods and
      plants in summer.
AB  - Top-down effects of predators can have important consequences for ecosystems.
      Insectivorous birds frequently have strong predation effects on herbivores and
      other arthropods, as well as indirect effects on herbivores' host plants. Diet
      studies have shown that birds in temperate ecosystems consume arthropods in
      winter as well as in summer, but experimental studies of bird predation effects
      have not attempted to quantitatively separate winter predation impacts from those
      in summer. To understand if winter foraging by insectivorous birds has
      consequences for arthropods or plants, we performed a meta-analysis of published
      bird exclusion studies in temperate forest and shrubland habitats. We categorized
      85 studies from 41 publications by whether birds were excluded year-round or only
      in summer, and analyzed arthropod and plant response variables. We also performed
      a manipulative field experiment in which we used a factorial design to exclude
      birds from Quercus velutina Lam. saplings in winter and summer, and censused
      arthropods and herbivore damage in the following growing season. In the meta
      analysis, birds had stronger negative effects on herbivores in studies that
      included winter exclusion, and this effect was not due to study duration.
      However, this greater predation effect did not translate to a greater impact on
      plant damage or growth. In the field experiment, winter exclusion did not
      influence herbivore abundance or their impacts on plants. We have shown that
      winter feeding by temperate insectivorous birds can have important consequences
      for insect herbivore populations, but the strength of these effects may vary
      considerably among ecosystems. A full understanding of the ecological roles of
      insectivorous birds will require explicit consideration of their foraging in the
      non-growing season, and we make recommendations for how future studies can
      address this.

PMID- 22644052
TI  - Osmotic and elastic adjustments in cold desert shrubs differing in rooting depth:
      coping with drought and subzero temperatures.
AB  - Physiological adjustments to enhance tolerance or avoidance of summer drought and
      winter freezing were studied in shallow- to deep-rooted Patagonian cold desert
      shrubs. We measured leaf water potential (Psi(L)), osmotic potential, tissue
      elasticity, stem hydraulic characteristics, and stomatal conductance (g (S))
      across species throughout the year, and assessed tissue damage by subzero
      temperatures during winter. Species behavior was highly dependent on rooting
      depth. Substantial osmotic adjustment (up to 1.2 MPa) was observed in deep-rooted
      species exhibiting relatively small seasonal variations in Psi(L) and with access
      to a more stable water source, but having a large difference between predawn and
      midday Psi(L). On the other hand, shallow-rooted species exposed to large
      seasonal changes in Psi(L) showed limited osmotic adjustment and incomplete
      stomatal closure, resulting in turgor loss during periods of drought. The bulk
      leaf tissue elastic modulus (epsilon) was lower in species with relatively
      shallow roots. Daily variation in g (S) was larger in shallow-rooted species
      (more than 50 % of its maximum) and was negatively associated with the difference
      between Psi(L) at the turgor loss point and minimum Psi(L) (safety margin for
      turgor maintenance). All species increased epsilon by about 10 MPa during winter.
      Species with rigid tissue walls exhibited low leaf tissue damage at -20  degrees
      C. Our results suggest that osmotic adjustment was the main water relationship
      adaptation to cope with drought during summer and spring, particularly in deep
      rooted plants, and that adjustments in cell wall rigidity during the winter
      helped to enhance freezing tolerance.

PMID- 22644053
TI  - Performance of a novel microarray multiplex PCR for the detection of 23
      respiratory pathogens (SYMP-ARI study).
AB  - Symptoms of acute febrile respiratory tract infection are often unspecific, but
      the rapid identification of pathogens allows optimised patient management. The
      objective of this study was to evaluate a novel multiplex polymerase chain
      reaction (PCR) suspension microarray which detects 19 viral and four atypical
      bacterial targets. A comprehensive set of sensitive monoplex real-time PCR assays
      was used for each pathogen as the gold standard. A panel of archived as well as
      300 prospectively collected clinical samples was analysed by both methods. At
      least one target was detected in 165/300 (55 %) samples by monoplex PCR and in
      140/300 (46 %) samples by multiplex PCR, respectively. The positivity rate was
      significantly higher in paediatric patients compared to adults [126/154 (82 %)
      vs. 39/146 (27 %) by monoplex and 114/154 (74 %) vs. 26/146 (18 %) by multiplex
      PCR, respectively]. Among all samples, 17/300 (5.6 %) were positive for atypical
      bacteria by monoplex and 8/300 (2.6 %) by multiplex PCR, respectively. Multiple
      detections were recorded in 35/300 (11.6 %) samples by monoplex and 26/300 (8.7
      %) by multiplex PCR. For the most common pathogens, the sensitivity ranged from
      57 to 93 % and the specificity ranged from 95 to 100 %. The overall concordance
      between both methods was 77 % [95 % confidence interval (CI) 72-81 %]. False
      negative results by multiplex PCR were mainly due to the low target
      concentration. Compared to monoplex PCR, the novel microarray assay proved its
      principle but displayed overall lower sensitivities, potentially restricting its
      use to paediatric patients. For some targets, only small numbers of positive
      samples were available, requiring larger studies to firmly assess the sensitivity
      and specificity.

PMID- 22644054
TI  - Regional variations in quinolone use in France and associated factors.
AB  - The purpose of this study was to investigate geographic variations in the use of
      quinolones in France and their associated factors. All reimbursement claims of
      antimicrobials were collected for 90 % of the French population for the year
      2007. Dispensed quantities were then converted into defined daily doses (DDD) and
      adjusted for the age structure of the national population. Correlations between
      quinolone use and total antimicrobial use and some morbidity and socio-economic
      factors were studied using Spearman's rank correlation coefficients. On average,
      2.05 DDD of quinolones per 1,000 inhabitants per day (DID) were dispensed in 2007
      in France, accounting for 10.2 % of the total antimicrobial consumption in
      adults. A 40 % variation was observed between the regions with the lowest (1.73
      DID) and the highest use (2.44 DID). This variation was more important for anti
      pneumococcal quinolones than for quinolones directed against urinary tract
      infections (coefficients of variation: 26 vs. 6 %). Quinolone use was correlated
      with some regional socio-economic factors (unemployment, growth domestic product,
      health expenditures) and physician density, but was independent of the total
      antimicrobial use. After adjustment for age, large variations in quantitative and
      qualitative quinolone use were observed across French regions, especially for
      anti-pneumococcal fluoroquinolones. These results, though not controlled for
      potential epidemics variations, argue in favour of a possible improvement in
      quinolone prescribing to be achieved in some regions.

PMID- 22644055
TI  - MALDI-TOF mass spectrometry and microsatellite markers to evaluate Candida
      parapsilosis transmission in neonatal intensive care units.
AB  - Recent studies on outbreaks of Candida showed an increased incidence of
      bloodstream infections in neonatal intensive care units (NICUs) caused by C.
      parapsilosis species, highlighting the need for the proper identification and
      epidemiology of these species. Several systems are available for molecular
      epidemiological and taxonomic studies of fungal infections: pulsed-field gel
      electrophoresis (PFGE) represents the gold standard for typing, but is also one
      of the most lengthy and expensive, while simple sequence repeats (SSRs) is based
      on polymerase chain reaction (PCR) amplification and is, therefore, faster. Only
      recently, matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) has been used to identify and type microorganisms
      involved in nosocomial outbreaks. In our study, 19 strains of C. parapsilosis
      isolated from the blood cultures of neonates admitted to the University Hospital
      Federico II were genotyped by the amplification of eight SSR markers and by MALDI
      TOF MS. Electrophoretic and spectrometric profile results were compared in order
      to identify similarities among the isolates and to study microevolutionary
      changes in the C. parapsilosis population. The discriminatory power and the
      unweighted pair group method with arithmetic mean (UPGMA) dendrograms generated
      were compared in order to evaluate the correlation of the groups established by
      the analysis of the clusters by both methods. Both methods were rapid and
      effective in highlighting identical strains and studying microevolutionary
      changes in the population. Our study evidenced that mass spectroscopy is a useful
      technique not only for the identification but also for monitoring the spread of
      strains, which is critical to control nosocomial infections.

PMID- 22644056
TI  - Factors associated with recurrence of catheter-related bloodstream infections in
      home parenteral nutrition patients.
AB  - Blood cultures from outpatients receiving home parenteral nutrition (HPN) via
      long-term central venous access (CVA) were retrospectively analyzed from January
      2003 to May 2009. When infection of the CVA was not due to Staphylococcus aureus,
      Pseudomonas aeruginosa, or Candida, catheter salvage was attempted for a maximum
      of three consecutive infections on the same CVA. Factors influencing the time-to
      next-infection were studied, whether the catheter was changed after the last
      infection or not. Neither the McCabe score, age, history of cancer, diabetes
      mellitus nor immunosuppression, curative antibiotic lock, type of bacteria, type
      or duration of treatment had an influence on the time-to-next-infection. The time
      to-next-infection was significantly associated with the status of CVA (saved or
      changed) and its type (tunneled catheter with or without a cuff, or implanted
      port catheter).

PMID- 22644057
TI  - Outbreak analysis and typing of MRSA isolates by automated repetitive-sequence
      based PCR in a region with multiple strain types causing epidemics.
AB  - The usefulness and performance of repetitive-sequence-based polymerase chain
      reaction (rep-PCR), the DiversiLab system, in the epidemiological surveillance
      for methicillin-resistant Staphylococcus aureus (MRSA) strain typing was
      assessed. MRSA isolates from five distinct outbreaks with precise epidemiological
      data (n = 69) and from the culture collection of well-characterized MRSA strains
      (n = 132) consisting of 35 spa and 23 pulsed-field gel electrophoresis (PFGE)
      types were analyzed. The typing results of the DiversiLab system in outbreak
      analysis were compared to the spa and PFGE typing methods. The DiversiLab system
      proved to be a reliable tool for the rapid first-line typing of MRSA isolates,
      showing a good reliability in distinguishing MRSA strains in an area where
      several MRSA types were causing epidemics. This, however, required that the
      automatic clustering was combined with manual interpretation using the pattern
      overlay function when the strain types showing high similarity were clustered
      together. All outbreaks were distinguished with the DiversiLab system and the
      PFGE method, but not with the spa typing method. The overall discriminatory power
      of the DiversiLab system in differentiating diverse MRSA strains proved to be
      good. We also demonstrated that, in addition to the genetic relatedness analysis
      of MRSA strains, it is important to obtain accurate epidemiological information
      in order to perform reliable epidemiological surveillance studies.

PMID- 22644059
TI  - [The role of orthopedic surgeons in the treatment of fibromyalgia].

PMID- 22644058
TI  - Time to positivity of follow-up blood cultures in patients with persistent
      Staphylococcus aureus bacteremia.
AB  - We investigated the clinical usefulness of time to blood culture positivity (TTP)
      of follow-up positive blood cultures (FUPBC) in patients with persistent
      Staphylococcus aureus bacteremia (SAB). Of the patients who did not have
      resolution of SAB after primary therapeutic intervention (PTI), patients who had
      decreases in TTP of FUPBC after PTI more frequently experienced 30-day mortality
      or secondary foci of infection than those who did not have decrease in TTP (83.3%
      vs. 28.6%; p = 0.005).

PMID- 22644060
TI  - Spigel hernia: a single center experience in a rare hernia entity.
AB  - INTRODUCTION: Spigelian Hernia (SH) is a rare ventral hernia with a high
      incarceration and obstruction risk. The purpose of this study is to present our
      experience in diagnosis and treatment of this rare hernia entity. MATERIALS AND
      METHOD: Sixteen patients underwent surgery for SH between 2000 and 2010. Analysis
      parameters included demographic data, location of defect, diagnostic methods,
      mode of surgery, mode of anesthesia and postoperative outcome. RESULTS: Mean
      follow-up was 98 months. The gender bias was 37.5 %: 62.5 % (man: woman) with
      mean age of 56 years. The SH was right-sided in 56.25 %, left-sided in 37.5 % and
      bilateral in 6.25 % of the cases. The preoperative diagnosis was correct in 25 %
      of the cases. Eight patients (50 %) underwent elective surgery, and the other 8
      patients (50 %) underwent surgical treatment on emergency basis. Two patients
      underwent open hernia repair by primary suture, 13 patients underwent open mesh
      repair and one patient underwent a laparoscopic mesh repair. Neither a major
      hernia repair-related complication nor mortality could be registered. CONCLUSION:
      SH is a rare entity with a wide clinical spectrum and difficulties in
      preoperative diagnosis. Once the diagnosis of SH is established, a surgical
      treatment is indicated because of the high complication risk.

PMID- 22644061
TI  - Kidney-pancreas transplantation: assessment of key imaging findings in the acute
      setting.
AB  - For patients with diabetes, insulin therapy can be an effective treatment for
      years. However, many diabetics eventually develop complications from the disease,
      including neuropathy, amputations, atherosclerosis, and kidney failure. While
      kidney failure can be managed with dialysis, difficulties with monitoring fluid
      intake and diet, bone loss, anemia, and venous access can be problematic for the
      patient. Due to the decreased life expectancy and difficulties of medical
      management of patients with diabetes and renal failure, combined renal-pancreas
      transplantation is an increasingly used option available to type 1 diabetics with
      concurrent renal failure due to refinements of surgical technique and
      immunosuppressive therapy. Due to the increasing number of kidney-pancreas
      transplant patients, longer post-transplant survival, and increasing number of
      hospitals performing the procedure, more transplant patients are having their
      care increasingly shifted away from the major transplant centers to general
      community hospitals. In many kidney-pancreas transplants patients who present to
      the emergency department for suspected transplant dysfunction, imaging plays a
      critical initial role in their diagnosis and management. Therefore, it has become
      increasingly important that community and emergency department radiologists be
      able to recognize the normal imaging appearance of renal-pancreas transplants and
      to identify acute findings.

PMID- 22644062
TI  - Aqueous ammonia pretreatment, saccharification, and fermentation evaluation of
      oil palm fronds for ethanol production.
AB  - Oil palm fronds are the most abundant lignocellulosic biomass in Malaysia. In
      this study, fronds were tested as the potential renewable biomass for ethanol
      production. The soaking in aqueous ammonia pretreatment was applied, and the
      fermentability of pretreated fronds was evaluated using simultaneous
      saccharification and fermentation. The optimal pretreatment conditions were 7 %
      (w/w) ammonia, 80  degrees C, 20 h of pretreatment, and 1:12 S/L ratio, where the
      enzymatic digestibility was 41.4 % with cellulase of 60 FPU/g-glucan. When
      increasing the cellulase loading in the hydrolysis of pretreated fronds, the
      enzymatic digestibility increased until the enzyme loading reached 60 FPU/g
      glucan. With 3 % glucan loading in the SSF of pretreated fronds, the ethanol
      concentration and yield based on the theoretical maximum after 12 and 48 h of the
      SSF were 7.5 and 9.7 g/L and 43.8 and 56.8 %, respectively. The ethanol
      productivities found at 12 and 24 h from pretreated fronds were 0.62 and 0.36
      g/L/h, respectively.

PMID- 22644063
TI  - Bio-hydrogen production by biodiesel-derived crude glycerol bioconversion: a
      techno-economic evaluation.
AB  - Global biodiesel production is continuously increasing and it is proportionally
      accompanied by a huge amount of crude glycerol (CG) as by-product. Due to its
      crude nature, CG has very less commercial interest; although its pure counterpart
      has different industrial applications. Alternatively, CG is a very good carbon
      source and can be used as a feedstock for fermentative hydrogen production.
      Further, a move of this kind has dual benefits, namely it offers a sustainable
      method for disposal of biodiesel manufacturing waste as well as produces biofuels
      and contributes in greenhouse gas (GHG) reduction. Two-stage fermentation,
      comprising dark and photo-fermentation is one of the most promising options
      available for bio-hydrogen production. In the present study, techno-economic
      feasibility of such a two-stage process has been evaluated. The analysis has been
      made based on the recent advances in fermentative hydrogen production using CG as
      a feedstock. The study has been carried out with special reference to North
      American biodiesel market; and more specifically, data available for Canadian
      province, Quebec City have been used. Based on our techno-economic analysis,
      higher production cost was found to be the major bottleneck in commercial
      production of fermentative hydrogen. However, certain achievable alternative
      options for reduction of process cost have been identified. Further, the process
      was found to be capable in reducing GHG emissions. Bioconversion of 1 kg of crude
      glycerol (70 % w/v) was found to reduce 7.66 kg CO(2) eq (equivalent) GHG
      emission, and the process also offers additional environmental benefits.

PMID- 22644064
TI  - Evaluation of an electronic nose for the early detection of organic overload of
      anaerobic digesters.
AB  - This study aimed at analysing the utilization of an electronic nose (e-nose) to
      serve as a specific monitoring tool for anaerobic digestion process, especially
      for detecting organic overload. An array of non specific metal oxide
      semiconductor gas sensors were used to detect process faults due to organic
      overload events in twelve 1.8-L anaerobic semi-continuous reactors. Three
      different load strategies were followed: (1) a cautious organic load (1.3 gVS L(
      1) day(-1)); (2) an increasing load strategy (1.3-5.3 gVS L(-1) day(-1)) and (3)
      a cautious organic load with load pulses of up to 12 gVS L(-1) day(-1). A first
      monitoring campaign was conducted with three different substrates: sucrose, maize
      oil and a mix of sucrose/oil during 60 days. The second campaign was run with dry
      sugar beet pulp for 45 days. Hotelling's T(2) value and upper control limit to a
      reference set of digesters fed with a cautious OLR (1.3 gVS L(-1) day(-1)) was
      used as indirect state variable of the reactors. Overload situations were
      identified by the e-nose apparatus with Hotelling's T(2) values at least four
      times higher in magnitude than the upper control limit of 23.7. These results
      confirmed that the e-nose technology appeared promising for online detection of
      process imbalances in the domain of anaerobic digestion.

PMID- 22644065
TI  - Oxaloacetate and malate production in engineered Escherichia coli by expression
      of codon-optimized phosphoenolpyruvate carboxylase2 gene from Dunaliella salina.
AB  - A new phosphoenolpyruvate carboxylase (PEPC) gene of Dunaliella salina is
      identified using homology analysis was conducted using PEPC gene of Chlamydomonas
      reinhardtii and Arabidopsis thaliana. Recombinant E. coli SGJS115 with increased
      production of malate and oxaloacetate was developed by introducing codon
      optimized phosphoenolpyruvate carboxylase2 (OPDSPEPC2) gene of Dunaliella salina.
      E. coli SGJS115 yielded a 9.9 % increase in malate production. In addition, E.
      coli SGJS115 exhibited two times increase in the yield of oxaloacetate over the
      E. coli SGJS114 having identified PEPC2 gene obtained from Dunaliella salina.

PMID- 22644068
TI  - High acceptability of a vaginal ring intended as a microbicide delivery method
      for HIV prevention in African women.
AB  - Vaginal rings (VRs) are new methods for continuous delivery of microbicides. This
      is the first study to quantitatively and qualitatively explore the acceptability
      of rings in Africa: 157 HIV-negative, sexually active women aged 18-35 used a
      placebo silicone elastomer ring for 12 weeks. They completed product
      acceptability questionnaires every 4 weeks. We conducted 6 exit focus group
      discussions with a subset of 48 women and 19 in-depth interviews with male
      partners. Retention in the study was high (97 %). Initial insertion at the clinic
      was successful on first attempt for 81 % of participants. Most women were
      comfortable using the ring, and very few (<=2 %) could feel it during daily
      activities or had ring-related physical or emotional problems. In the qualitative
      interviews many participants reported that they initially had concerns about
      using the ring. However, only a minority of women actually reported concerns with
      the ring during the study. The most frequent concern was that the ring would get
      lost inside the body (20 %), and this was significantly correlated with study
      site, frequently thinking about the ring and reporting that the ring was not very
      easy to remove. Qualitative data suggest that informants grew to like the ring
      because it felt securely placed, was unnoticeable during daily activities, and
      felt "normal" during sex. The ring appeared to be highly acceptable for women and
      men. Initial concerns with this novel method suggest a need for enhanced product
      counseling when VRs are introduced.

PMID- 22644067
TI  - Seroadaptation in a sample of very poor Los Angeles area men who have sex with
      men.
AB  - Data from 635 very poor men who have sex with men (MSM) were used to identify
      seroadaptation with 1,102 male partners reported between 2005 and 2007 in Los
      Angeles as part of the Sexual Acquisition and Transmission of HIV Cooperative
      Agreement Program. The mean age of the sample was 41.7 years; 53 % had
      experienced homelessness in the past year. Condoms were reported in 51 % of
      sexual events involving anal intercourse. HIV seroconcordance was reported in 41
      % of sexual partnerships among HIV-positive participants. HIV-positive men were
      more likely to have oral-only or unprotected receptive anal intercourse and less
      likely to have unprotected insertive anal intercourse with HIV-negative or
      unknown partners compared to HIV-positive partners. Even in the face of poverty,
      HIV-positive MSM report mitigating risks of HIV-transmission though
      seroadaptation in the context of modest rates of condom use.

PMID- 22644066
TI  - The impact of DSM-IV mental disorders on adherence to combination antiretroviral
      therapy among adult persons living with HIV/AIDS: a systematic review.
AB  - This is a systematic review of eighty-two published studies investigating the
      impact of DSM-IV mental disorders on combination antiretroviral therapy (cART)
      adherence and persistence among persons living with HIV/AIDS (PLWHA). Sixty-two
      articles examined depression, with 58 % (N = 32/62) finding lower cART adherence
      and persistence. Seventeen articles examined one or more anxiety disorders, with
      the majority finding no association with cART adherence or persistence. Eighty
      percent of the studies that evaluated the impact of psychotic (N = 3), bipolar (N
      = 5) and personality disorders (N = 2) on cART adherence and persistence also
      found no association. Seven out of the nine studies (78 %) evaluating the impact
      of antidepressant treatment (ADT) on cART adherence found improvement. Adherence
      and depression measurements varied significantly in studies; common research
      measurements would improve data harmonization. More research specifically
      addressing the impact of other mental disorders besides depression on cART
      adherence and RCTs evaluating ADT on cART adherence are also needed.

PMID- 22644069
TI  - The utility of interventional pulmonary procedures in liberating patients with
      malignancy-associated central airway obstruction from mechanical ventilation.
AB  - PURPOSE: Utilization of intensive care services by patients with malignancy has
      risen during the past several decades. Newer cancer therapies have improved
      overall survival and outcomes. Patients with respiratory failure from central
      airway obstruction related to tumor growth were previously viewed as
      inappropriate candidates for ventilator support. However, an increasing number of
      reports suggest that interventional pulmonary (IP) procedures may benefit such
      patients. METHODS: We reviewed the literature for case reports or case series
      from the past 20 years regarding the use of IP procedures for the treatment of
      respiratory failure from malignancy-associated central airway obstruction.
      RESULTS: As a whole, IP procedures were greater than 60 % successful in
      liberating patients from mechanical ventilation. Moreover, IP procedures served
      to palliate respiratory symptoms, prolong overall survival, allow for additional
      cancer treatments, and reduce hospitalization costs. Nevertheless, it remains
      unclear who may benefit the most from these procedures. CONCLUSIONS: Although
      data are limited, IP procedures are generally safe and should be considered for
      appropriate patients with respiratory failure from malignancy-associated central
      airway obstruction as a potential means of liberation from mechanical
      ventilation.

PMID- 22644070
TI  - Predictive factors for response to treatment in patients with advanced renal cell
      carcinoma.
AB  - INTRODUCTION: The analysis of predictive factors of response may aid in
      predicting which patients with advanced renal cell carcinoma (RCC) would be good
      candidates for systemic treatments. MATERIALS AND METHODS: The expression of
      several biomarkers was retrospectively analyzed using immunohistochemistry (IHC),
      as well as 2 analytical variables in 135 patients with advanced RCC treated with
      cytokines (CK) and/or new targeted drugs (NTD). RESULTS: 67 patients were treated
      solely with NTD and 68 with CK (23 also received NTD). Univariate analysis:
      HIF1alpha did not correlate significantly with response to these drugs.
      Overexpression of CAIX was associated with more responses (%) to NTD (64.7 vs.
      21.1; p = 0.004) and CK (22.6 vs. 0; p = 0.038). PTEN demonstrated predictive
      value of response to sunitinib (70.8 vs. 34.1; p = 0.005). p21 was associated
      with a lower response to sunitinib (35.9 vs. 65.4; p = 0.025). Thrombocytosis was
      not significantly associated with response to NTD, although it was with CK (0 vs.
      20; p = 0.017). Neutrophilia correlated with a lower response to NTD (29.6 vs.
      57.5; p = 0.045), although not with CK. Multivariate analysis: Overexpression of
      CAIX was an independent predictor of significantly higher response to NTD and CK;
      OR = 8.773 (p < 0.001). CONCLUSIONS: Our findings highlight the usefulness of
      CAIX in selecting patients with advanced RCC as candidates for systemic
      treatment. PTEN and p21 may be important in predicting response to sunitinib.
      Thrombocytosis and neutrophilia correlate well with response to CK and NTD,
      respectively.

PMID- 22644071
TI  - Monoplanar versus biplanar medial open-wedge proximal tibial osteotomy for varus
      gonarthrosis: a comparison of clinical and radiological outcomes.
AB  - PURPOSE: We compared clinical and radiological results of two proximal tibial
      osteotomy (PTO) techniques: monoplanar medial open-wedge osteotomy and biplanar
      retrotubercle medial open-wedge osteotomy, stabilised by a wedged plate. METHODS:
      We evaluated 88 knees in 78 patients. Monoplanar medial open-wedge PTO was
      performed on 56 knees in 50 patients with a mean age of 55 +/- 9 years. Biplanar
      retrotubercle medial open-wedge PTO was performed on 32 knees in 28 patients with
      a mean age of 57 +/- 7 years. Mean follow-up periods were 40.6 +/- 7 months for
      the monoplanar PTO group and 38 +/- 5 months for the biplanar retrotubercle PTO
      group. Clinical outcome was evaluated using the hospital for special surgery
      scoring system, and radiological outcome was evaluated by the measurements of
      femorotibial angle (FTA), patellar height and tibial slope changes. RESULTS: In
      both groups, post-operative HSS scores increased significantly. No significant
      difference was found between groups in FTA alteration, but the FTA decreased
      significantly in both groups. Patellar index ratios decreased significantly in
      the monoplanar PTO group (Insall-Salvati Index by 0.07, Blackburne-Peel Index by
      0.07), but not in the biplanar retrotubercle PTO group. Tibial slopes were
      increased significantly in the monoplanar PTO group, but not in the retrotubercle
      PTO group. CONCLUSIONS: Biplanar retrotubercle medial open-wedge osteotomy and
      monoplanar medial open-wedge osteotomy are both clinically effective for the
      treatment for varus gonarthrosis. Retrotubercle osteotomy also prevents patella
      infera and tibial slope changes radiologically.

PMID- 22644072
TI  - Reliability of the 6-min walk test after total knee arthroplasty.
AB  - PURPOSE: The 6-min walk test is a simple clinical outcome measure, which has been
      used frequently to assess functional performance in many different patient
      groups, including patients with total knee arthroplasty (TKA). The 6-min walk
      test measures the maximal distance a subject is able to walk in 6 min. The
      reliability is unknown in patients with TKA. Therefore, the purpose of the study
      was to assess the reliability of the 6-min walk test in patients with recent TKA.
      METHODS: Thirty-four patients with TKA performed 2 test trials the same day,
      separated by a 1-h seated rest. To assess reliability, intra-class correlation
      coefficient (ICC2,1), standard error of measurement (SEM), and smallest real
      difference (SRD) were calculated. RESULTS: The patients walked on average 14.1 m
      longer at the second (397.2 m) compared to the first (383.1 m) test trial. The
      ICC2,1, SEM, and SRD were 0.97, 13.0, and 36.1 m, respectively. CONCLUSIONS: The
      intra-tester reliability of the 6-min walk test was high in patients with TKA.
      The thresholds of the 6-min walk test to detect a real change are acceptable in
      research (SEM) and clinical settings (SRD). We recommend that the longest
      distance walked in 2 supervised test trials should be used.

PMID- 22644073
TI  - Significant effect of the posterior tibial slope and medial/lateral ligament
      balance on knee flexion in total knee arthroplasty.
AB  - PURPOSE: The intra-operative femorotibial joint gap and ligament balance, the
      predictors affecting these gaps and their balances, as well as the postoperative
      knee flexion, were examined. These factors were assessed radiographically after a
      posterior cruciate-retaining total knee arthroplasty (TKA). The posterior
      condylar offset and posterior tibial slope have been reported as the most
      important intra-operative factors affecting cruciate-retaining-type TKAs. The
      joint gap and balance have not been investigated in assessments of the posterior
      condylar offset and the posterior tibial slope. METHODS: The femorotibial gap and
      medial/lateral ligament balance were measured with an offset-type tensor. The
      femorotibial gaps were measured at 0 degrees , 45 degrees , 90 degrees  and 135
      degrees  of knee flexion, and various gap changes were calculated at 0 degrees 
      90 degrees  and 0 degrees -135 degrees . Cruciate-retaining-type arthroplasties
      were performed in 98 knees with varus osteoarthritis. RESULTS: The 0 degrees -90
      degrees  femorotibial gap change was strongly affected by the posterior condylar
      offset value (postoperative posterior condylar offset subtracted by the
      preoperative posterior condylar offset). The 0 degrees -135 degrees  femorotibial
      gap change was significantly correlated with the posterior tibial slope and the
      135 degrees  medial/lateral ligament balance. The postoperative flexion angle was
      positively correlated with the preoperative flexion angle, gamma angle and the
      posterior tibial slope. Multiple-regression analysis demonstrated that the
      preoperative flexion angle, gamma angle, posterior tibial slope and 90 degrees 
      medial/lateral ligament balance were significant independent factors for the
      postoperative knee flexion angle. The flexion angle change (postoperative flexion
      angle subtracted by the preoperative flexion angle) was also strongly correlated
      with the preoperative flexion angle, posterior tibial slope and 90 degrees 
      medial/lateral ligament balance. CONCLUSION: The postoperative flexion angle is
      affected by multiple factors, especially in cruciate-retaining-type TKAs.
      However, it is important to pay attention not only to the posterior tibial slope,
      but also to the flexion medial/lateral ligament balance during surgery. A
      cruciate-retaining-type TKA has the potential to achieve both stability and a
      wide range of motion and to improve the patients' activities of daily living.

PMID- 22644074
TI  - Triple tibial osteotomy for the correction of severe bilateral varus deformity in
      a patient with late-onset Blount's disease.
AB  - A 14-year-old girl suffering from severe bilateral late-onset Blount's disease
      was treated by triple proximal tibial osteotomy. Surgical procedures included
      dome, respectively, closing wedge valgus osteotomy of the tibia, elevating
      osteotomy of the medial tibial plateau and lateralising osteotomy of the anterior
      tibial tuberosity. Mechanical leg axis was restored close to normal, the
      depression of the medial tibial plateau corrected and the extensor apparatus of
      the knee realigned. At 7.5 (right side) and 5.5 (left side) months of follow-up,
      all osteotomies had radiologically consolidated and the patient did not complain
      of knee pain or instability. Level of evidence IV.

PMID- 22644075
TI  - Return to judo after joint replacement.
AB  - PURPOSE: The main purpose of this study was to investigate whether judo could be
      practised after joint replacement. METHODS: Two hundred and twelve questionnaires
      were sent to Judokas licensed at the French Judo Federation, over the age of 60,
      with at least a black belt 6th Dan. Out of 83 responses, 38 individuals, mean age
      72.8 +/- 7.9 years old, had at least one implant. The survey identified 36 total
      hip arthroplasties (THA) in 27 patients, 10 total knee arthroplasties (TKA) in 8
      patients and 3 total shoulder arthroplasties (TSA) in 3 patients. The main
      evaluation criterion was the return to judo after joint replacement. Secondary
      criteria were the level of judo after surgery, rate of surgical revision at the
      final follow-up and the level of patient satisfaction. RESULTS: Twenty-nine out
      of 38 patients who underwent joint replacement returned to judo practice (76.3 %)
      a mean 4.1 +/- 2.9 months after surgery. On the other hand, all patients stopped
      competitive judo. The surgeon recommended 65.8 % of these patients to stop
      practising judo. There were 2 surgical revisions in the THA group (5.5 %) for
      loosening at 6 and 9 years of follow-up. No dislocations or fractures were
      reported at the final follow-up. Thirty-two patients (84.2 %) were satisfied with
      their implant. CONCLUSION: The practice of judo does not seem to be limited by
      joint replacement. A clinical and radiological study should be performed to
      confirm these results.

PMID- 22644076
TI  - Dislocation arthropathy and drill hole appearance in a mid- to long-term follow
      up study after arthroscopic Bankart repair.
AB  - PURPOSE: The aim of this study was to perform a prospective mid- to long-term
      clinical and radiographic follow-up after arthroscopic Bankart repair using
      absorbable tacks with special emphasis on the development of dislocation
      arthropathy. METHODS: Thirty-four shoulders in 32 patients with post-traumatic
      shoulder instability were included in the study. Clinical and radiographic follow
      ups took place after approximately 2 and 8 years. RESULTS: Thirty-four of 34 (100
      %) shoulders in 32 patients returned for the follow-up examination after 95 (53
      129) months. Pre-operatively, none of the shoulders had any arthropathy changes.
      At follow-up, 8/34 (24 %) had minor changes, 6/34 (18 %) had moderate changes,
      and none had severe arthropathy changes, a significant increment compared with
      the pre-operative figures (p = 0.005). At follow-up, the drill holes in 24 % of
      the shoulders still had not healed radiographically. The failure rate in terms of
      stability was 3/34 (9 %) re-dislocations and 3/34 (9 %) subluxations. CONCLUSION:
      Eight years after arthroscopic Bankart repair using absorbable tacks, 41 % of the
      shoulders displayed some degree of radiographic arthropathy changes and in 24 %
      the drill holes had not yet radiographically healed. There was no correlation
      between clinical outcome or drill hole appearance and the development of
      arthropathy changes. LEVEL OF EVIDENCE: III.

PMID- 22644077
TI  - Depressive symptoms in addition to visual impairment, reduced strength and poor
      balance predict falls in older Taiwanese people.
AB  - OBJECTIVE: to determine whether depression is an important and independent
      predictor of falls in community-dwelling older people living in Taiwan. DESIGN:
      longitudinal study. SETTING: five randomly selected villages from Tainan city,
      Taiwan. PARTICIPANTS AND METHODS: in total, 280 community-dwelling people not
      taking anti-depressant medication aged 65-91 years (mean age 74.9). Participants
      completed the Geriatric Depression Scale and underwent a range of sensorimotor,
      balance and mobility tasks and were then followed up for 2 years with monthly
      telephone calls to determine falls incidence. RESULTS: of the 260 participants
      with complete follow-up data, 174 (66.9%) experienced no falls, 51 (19.6%) fell
      once and 35 (13.5%) fell two or more times. Depressive symptoms were
      significantly more prevalent in recurrent fallers (40.0%) and once-only fallers
      (27.5%) compared with non-fallers (16.1%). Negative binomial regression analysis
      identified depression, poor depth perception, reduced lower limb strength and
      increased sway as independent and significant predictors of falls. CONCLUSION:
      depressive symptoms were found to be common in older Taiwanese people and
      associated with an increased fall risk. These findings suggest that in addition
      to implementing approaches to maximise vision, strength and balance, fall
      prevention strategies should also include interventions to assess and treat
      depression.

PMID- 22644078
TI  - Predicting readmissions: poor performance of the LACE index in an older UK
      population.
AB  - INTRODUCTION: interventions to prevent hospital readmission depend on the
      identification of patients at risk. The LACE index predicts readmission (and
      death) and is in clinical use internationally. The LACE index was investigated in
      an older UK population. METHODS: randomly selected alive-discharge episodes were
      reviewed. A LACE score was calculated for each patient and assessed using
      receiver operator characteristic (ROC) curves. A logistic regression model was
      constructed, compared with the LACE and validated in a separate population.
      RESULTS: a total of 507 patients were included with a mean (SD) age of 85 (6.5)
      years; 17.8% were readmitted and 4.5% died within 30 days. The median LACE score
      of those readmitted compared with those who were not was 12.5 versus 12 (P =
      0.13). The Lace index was only a fair predictor of both 30-day readmission and
      death with c-statistics of 0.55 and 0.70, respectively. Only the emergency
      department visit was an independent predictor of readmission, with a c-statistic
      of 0.61 for readmission. In a validation cohort of 507 cases, the c-statistic of
      the regression model was 0.57. CONCLUSION: the LACE index is a poor tool for
      predicting 30-day readmission in older UK inpatients. The absence of a simple
      predictive model may limit the benefit of readmission avoidance strategies.

PMID- 22644079
TI  - Regulation of actin cytoskeleton by Rap1 binding to RacGEF1.
AB  - Rap1 is rapidly and transiently activated in response to chemoattractant
      stimulation and helps establish cell polarity by locally modulating
      cytoskeletons. Here, we investigated the mechanisms by which Rap1 controls actin
      cytoskeletal reorganization in Dictyostelium and found that Rap1 interacts with
      RacGEF1 in vitro and stimulates F-actin polymerization at the sites where Rap1 is
      activated upon chemoattractant stimulation. Live cell imaging using GFP-coronin,
      a reporter for F-actin, demonstrates that cells expressing constitutively active
      Rap1 (Rap1CA) exhibit a high level of F-actin uniformly distributed at the cortex
      including the posterior and lateral sides of the chemotaxing cell. Examination of
      the localization of a PH-domain containing PIP3 reporter, PhdA-GFP, and the
      activation of Akt/Pkb and other Ras proteins in Rap1CA cells reveals that
      activated Rap1 has no effect on the production of PIP3 or the activation of
      Akt/Pkb and Ras proteins in response to chemoattractant stimulation. Rac family
      proteins are crucial regulators in actin cytoskeletal reorganization. In vitro
      binding assay using truncated RacGEF1 proteins shows that Rap1 interacts with the
      DH domain of RacGEF1. Taken together, these results suggest that Rap1-mediated F
      actin polymerization probably occurs through the Rac signaling pathway by
      directly binding to RacGEF1.

PMID- 22644080
TI  - Clinical effectiveness of neuraminidase inhibitors--oseltamivir, zanamivir,
      laninamivir, and peramivir--for treatment of influenza A(H3N2) and A(H1N1)pdm09
      infection: an observational study in the 2010-2011 influenza season in Japan.
AB  - The clinical effectiveness of the newly released neuraminidase inhibitors (NAIs)
      laninamivir and peramivir has not been sufficiently evaluated in influenza
      infected patients in clinical and practical settings. In this study, we analyzed
      the clinical data of 211 patients infected with influenza A virus subtype H3N2
      (A(H3N2)) and 45 patients infected with influenza A virus subtype H1N1pdm
      (A(H1N1)pdm09) who received the NAIs oseltamivir, zanamivir, laninamivir, or
      peramivir during the 2010-2011 influenza season. The duration of fever from the
      first dose of the NAI to fever alleviation to <37.5  degrees C was evaluated as
      an indicator of the clinical effectiveness of the NAIs in the influenza-infected
      patients. For the A(H3N2)-infected patients, Kaplan-Meier analysis showed the
      peramivir treatment group had the fastest time of fever alleviation to <37.5 
      degrees C (median 17.0 h, 95 % confidence interval [CI] 7.2-26.8 h) of the four
      treatment groups. No significant difference was found in the time to fever
      alleviation among the other antivirals, oseltamivir, zanamivir, and laninamivir.
      Results of multivariate analysis, using a Cox proportional-hazards model (hazard
      ratio 3.321) adjusted for the factors age, sex, body weight, vaccination status,
      time from onset to the clinic visit, and body temperature showed significantly
      faster fever alleviation in the peramivir treatment group compared with the
      oseltamivir treatment group. For the A(H1N1)pdm09-infected patients, only the
      oseltamivir and zanamivir treatment groups were compared, and no significant
      difference in time to alleviation of fever was observed between the two groups.
      Based on a cycling probe real-time polymerase chain reaction (PCR) assay, none of
      the A(H1N1)pdm09 strains in this study had the H275Y mutation conferring
      oseltamivir resistance. Further evaluation of the clinical effectiveness of the
      newly released NAIs for influenza-infected patients, including those infected
      with A(H1N1)pdm09, is needed.

PMID- 22644081
TI  - Use of high-dose IV and aerosolized colistin for the treatment of multidrug
      resistant Acinetobacter baumannii ventilator-associated pneumonia: do we really
      need this treatment?
AB  - In this study we aimed to assess the safety and efficacy of high-dose IV colistin
      (COL) and aerosolized COL for the treatment of Acinetobacter baumannii ventilator
      associated pneumonia (VAP). Critically ill adult patients who received IV COL for
      multidrug-resistant A. baumannii VAP were evaluated retrospectively. A total of
      45 patients were evaluated [15 patients with high-dose COL (2.5 mg/kg every 6 h),
      20 patients with normal dose (2.5 mg/kg every 12 h), and 10 patients with low
      dose, determined according to creatine clearance]. Aerosolized COL was used in 29
      patients treated with parenteral COL and 16 patients received only parenteral
      COL. The clinical response rates on the fifth day were 50, 30, and 27 % with the
      normal, low, and high doses, respectively. However, the clinical response rates
      at the end of the therapy had declined to 30, 30, and 7 % with the normal, low,
      and high doses, respectively. The bacteriological clearance rates at the end of
      the therapy were 65, 75, and 64 %, with the normal, low, and high doses,
      respectively. With the aerosolized COL, the clinical response rates on the fifth
      day and at the end of the therapy were 35 and 14 %, whereas these rates were 44
      and 38 % without the aerosolized COL. Bacteriological clearance rates with and
      without the aerosolized COL were 76 and 69 %, respectively. The nephrotoxicity
      rate was 40 % for the high-dose COL, whereas it was 35 % for the normal dose, and
      20 % for the low-dose COL. In conclusion, higher doses of COL and aerosolized COL
      had no advantages over lower doses in alleviating multidrug-resistant A.
      baumannii VAP. Moreover, the higher doses and the aerosolized COL increased the
      nephrotoxicity risk and seemed not to be safe.

PMID- 22644082
TI  - Pharmacokinetics of ampicillin-sulbactam and the renal function-based
      optimization of dosing regimens for prophylaxis in patients undergoing
      cardiovascular surgery.
AB  - Surgical site infections are a major cause of postoperative morbidity and
      mortality in cardiovascular surgery. Proper antibiotic prophylaxis can reduce the
      rate of such infections, but the concentration of antibiotic must be maintained
      at an adequate level throughout the operation. This study aimed to use renal
      function to determine the most appropriate timing for intraoperative repeated
      dosing of ampicillin-sulbactam, a commonly used prophylactic antibiotic, to
      maintain adequate concentrations throughout the course of surgery. The mean
      volume of distribution, elimination rate constant, elimination half-life, and
      total clearance of ampicillin were 13.2 l, 0.652 h-1, 1.32 h, and 8.45 l/h,
      respectively. A statistically significant (P < 0.0001) correlation (r = 0.771)
      was observed between the total clearance of ampicillin and creatinine clearance
      of the patients. Plasma concentrations of ampicillin were simulated with the
      pharmacokinetic parameters obtained. We developed a nomogram for adjusting the
      dosing interval according to renal function and predicted ampicillin trough
      concentrations. We revealed the best dosage and dosing interval for
      cardiovascular surgery by analyzing the perioperative pharmacokinetics of
      ampicillin-sulbactam administered prophylactically. We suggest that the dosage
      and dosing interval for ampicillin-sulbactam should be adjusted to optimize
      treatment efficacy and safety, on the basis of the MIC90 of methicillin-sensitive
      Staphylococcus aureus (MSSA) in each institution. TRIAL REGISTRATION:
      UMIN000007356.

PMID- 22644083
TI  - The quality implementation framework: a synthesis of critical steps in the
      implementation process.
AB  - Implementation science is growing in importance among funders, researchers, and
      practitioners as an approach to bridging the gap between science and practice. We
      addressed three goals to contribute to the understanding of the complex and
      dynamic nature of implementation. Our first goal was to provide a conceptual
      overview of the process of implementation by synthesizing information from 25
      implementation frameworks. The synthesis extends prior work by focusing on
      specific actions (i.e., the "how to") that can be employed to foster high quality
      implementation. The synthesis identified 14 critical steps that were used to
      construct the Quality Implementation Framework (QIF). These steps comprise four
      QIF phases: Initial Considerations Regarding the Host Setting, Creating a
      Structure for Implementation, Ongoing Structure Once Implementation Begins, and
      Improving Future Applications. Our second goal was to summarize research support
      for each of the 14 QIF steps and to offer suggestions to direct future research
      efforts. Our third goal was to outline practical implications of our findings for
      improving future implementation efforts in the world of practice. The QIF's
      critical steps can serve as a useful blueprint for future research and practice.
      Applying the collective guidance synthesized by the QIF to the Interactive
      Systems Framework for Dissemination and Implementation (ISF) emphasizes that
      accountability for quality implementation does not rest with the practitioner
      Delivery System alone. Instead, all three ISF systems are mutually accountable
      for quality implementation.

PMID- 22644084
TI  - Swallowing in patients with Parkinson's disease: a surface electromyography
      study.
AB  - Our goal was to study deglutition of Parkinson's disease (PD) patients and normal
      controls (NC) using surface electromyography (sEMG). The study included 15
      patients with idiopathic PD and 15 age-matched normal controls. Surface
      electromyography was collected over the suprahyoid muscle group. Conditions were
      the following: swallow at once 10 and 20 ml of water and 5 and 10 ml of yogurt of
      firm consistency, and freely drink 100 ml of water. During swallowing, durations
      of sEMG were significantly longer in PD patients than in normal controls but no
      significant differences of amplitudes were found. Eighty percent of the PD
      patients and 20 % of the NC needed more than one swallow to consume 20 ml of
      water, while 70 % of the PD patients and none of the NC needed more than one
      swallow to consume 5 ml of yogurt. PD patients took significantly more time and
      needed significantly more swallows to drink 100 ml of water than normal controls.
      We conclude that sEMG might be a simple and useful tool to study and monitor
      deglutition in PD patients.

PMID- 22644085
TI  - Estimation of fetal age at death from the basilar part of the occipital bone.
AB  - The purposes of this study are to examine documented fetal skeletal remains of
      Japanese, to measure the basilar part of the occipital bone, and to develop
      diagnostic standards for estimating fetal age at death which can be applied to
      poorly preserved skeletons. The sample is composed of 272 Japanese individuals of
      the early to middle twentieth century, whose ages were recorded in months from
      gestations of 5 to 11 months. The measurement items used here are the length,
      breadth, and index of the basilar part. The regression equations of gestational
      age in months for one or two variables were calculated. The results indicated
      that it is possible to use the regression equations to estimate the age at death
      of fetuses directly from the basilar part measurements. Another indicator for
      estimating age at death from the basilar part is the ratio of the width to the
      length, which was here expressed as the index of the basilar part. The width
      exceeded the length at 7 months and the basilar part changed with age from an
      anteriorly posteriorly long shape to a bilaterally wide one. It is concluded that
      the basilar part is a good indicator for estimating the fetal age at death.

PMID- 22644086
TI  - The "inverted traffic light" obstetric difficult airway management algorithm.

PMID- 22644087
TI  - Serum leptin levels are associated with the presence of syndesmophytes in male
      patients with ankylosing spondylitis.
AB  - The aim of this study is to clarify the association between serum leptin levels
      and the presence of syndesmophytes in male patients with ankylosing spondylitis
      (AS). Seventy-two male patients with AS and 20 age-matched healthy male controls
      were included. Patients were stratified by the presence of syndesmophytes. Serum
      leptin levels were measured and adjusted for body mass index (BMI). In addition,
      bone-specific alkaline phosphatase (BALP), osteocalcin, and telopeptide of type I
      collagen were determined. Patients with syndesmophytes were associated with older
      age (p < 0.001), longer disease duration (p = 0.003), and higher BMI (p = 0.038).
      Serum leptin levels and leptin per BMI (leptin/BMI) ratio were not different
      between AS patients and healthy controls. However, serum leptin/BMI ratio was
      significantly higher in patients with syndesmophytes compared to those without (p
      = 0.010). In multivariate analysis, higher serum leptin/BMI ratio remained
      significantly associated with the presence of syndesmophytes (p = 0.029).
      Moreover, serum leptin/BMI ratio was positively correlated with serum BALP (gamma
      = 0.279, p = 0.039). However, there was no significant association between serum
      leptin/BMI ratio and bone mineral density. Serum leptin levels are elevated in
      male AS patients with syndesmophytes and were found to be correlated with bone
      formation marker, suggesting a potential role of leptin in new bone formation in
      AS.

PMID- 22644088
TI  - Beware of the biologicals--hospitals may die: the Rheumatism Foundation Hospital,
      Heinola, Finland (1951-2010).
AB  - The first patient entered the Rheumatism Foundation Hospital, Heinola, Finland in
      July 1951. From that point on, the hospital helped patients suffering from
      rheumatic disorders. Specialists in the hospital actively developed treatments
      and published a large number of scientific articles in international journals.
      The hospital was well known internationally among people working in the field.
      Progress in the development of disease-modifying medication (biological agents in
      particular) has dramatically improved the life of patients with rheumatic
      diseases, but all effective treatments may also have adverse effects. In this
      article, we briefly review the history of the Rheumatism Foundation Hospital,
      which was closed permanently in March 2010 due to bankruptcy. The economical
      difficulties were caused primarily by the progress made in disease-modifying
      therapy, which decreased the need of rehabilitation and operative treatment of
      patients with rheumatic diseases. It seems that a great success in biological
      agents can carry "serious adverse effects", which may kill hospitals. This is an
      important primary observation, which should be noticed when the future of
      specialised institutes is planned.

PMID- 22644089
TI  - Rituximab in a patient with ankylosing spondylitis with demyelinating disease: a
      case report and review of the literature.
AB  - Tumor necrosis factor inhibitors (TNFI) are novel therapies used to treat
      ankylosing spondylitis (AS). Demyelinating disease is a rare but serious
      complication of TNFI. We report a patient with a case of AS who developed
      demyelinating disease secondary to TNFI and was treated successfully with
      rituximab.

PMID- 22644090
TI  - Pauci-immune crescentic glomerulonephritis in limited cutaneous systemic
      sclerosis.
AB  - Pauci-immune necrotizing glomerulonephritis is a form of a rapidly progressive
      glomerulonephritis that is associated with the anti-neutrophil cytoplasmic
      antibodies (ANCA). ANCA-associated pauci-immune glomerulonephritis may be
      secondary to rheumatic diseases. We report on a patient with limited cutaneous
      systemic sclerosis who presented with subacute onset of nephritic syndrome and
      renal insufficiency. Her myeloperioxidase ANCA titer was elevated and renal
      biopsy confirmed pauci-immune crescentic glomerulonephritis, which was stabilized
      with high-dose glucocorticoid and cyclophosphamide. ANCA-associated necrotizing
      glomerulonephritis is rarely reported in systemic sclerosis and a systematic
      review is presented.

PMID- 22644091
TI  - High prevalence of winter 25-hydroxyvitamin D deficiency despite supplementation
      according to guidelines for hemodialysis patients.
AB  - BACKGROUND: There are seasonal variations in serum 25-hydroxyvitamin D (25OHD)
      levels related to sun exposure. Recent guidelines suggest a target serum 25OHD
      level >30 ng/ml in chronic kidney disease patients. However, vitamin D
      supplementation dosing and monitoring regimens are not well established in
      hemodialysis patients. The aim of this study was to assess the interplay between
      season and 25OHD supplementation according to guidelines on 25OHD levels in
      hemodialysis patients. METHODS: We retrospectively reviewed data collected
      prospectively over 12 months in 32 stable hemodialysis patients receiving 25OHD
      supplements (mean dose 30,600 IU/month) under routine clinical care following the
      Spanish Society of Nephrology guidelines. RESULTS: Higher serum 25OHD was
      observed during the summer, peaking in June and August. Despite a trend towards a
      higher 25OHD dose in winter the prevalence of 25OHD deficiency was still >40 % in
      winter. Furthermore, despite a higher dose of calcium-based phosphate binders,
      there was a trend toward lower serum calcium in winter. Season, together with
      residual diuresis and dry weight, was a significant independent contributor to a
      multivariate lineal regression model that explained 25 % of serum 25OHD
      variability, while a 25OHD dose did not contribute significantly in this 25OHD
      supplemented population. CONCLUSION: Winter vitamin D deficiency is prevalent in
      hemodialysis patients despite supplementation with 25OHD according to clinical
      guidelines. More intensive monitoring or pre-emptive winter dose increases should
      be evaluated to achieve guideline targets.

PMID- 22644092
TI  - Combined administration of low-dose prednisolone and cyclosporine in idiopathic
      membranous nephropathy: Tsukuba's regimen for IMN.

PMID- 22644093
TI  - Chronic toxicity of a laundry detergent to the freshwater flagellate Euglena
      gracilis.
AB  - Chronic toxicity of the common laundry detergent Ariel on the freshwater alga
      Euglena gracilis was investigated by growing the alga in a medium containing the
      detergent for 7 days. Cell density, motility, swimming velocity, gravitactic
      orientation, cell shape, photosynthesis and concentration of light-harvesting
      pigments were used as end point parameters for the assessment of toxicity. Cell
      density was significantly reduced at a concentration of 1 mg l(-1) or above.
      Among the other tested parameters, with the exception of cell shape, gravitaxis
      and chlorophyll b, all were adversely affected by the detergent at concentrations
      exceeding 1 mg l(-1). It is concluded that long-term (7-days) exposure to the
      detergent caused significant toxicity to E. gracilis. Furthermore, long-term
      tests with E. gracilis can be used as sensitive indicator for the toxicity
      assessment of laundry detergents in aquatic environments.

PMID- 22644095
TI  - Treatment of non-arteritic anterior ischemic optic neuropathy with high-dose
      systemic corticosteroids.

PMID- 22644094
TI  - Gene therapy for Leber congenital amaurosis: advances and future directions.
AB  - BACKGROUND: Leber congenital amaurosis (LCA) is a congenital retinal dystrophy
      that results in significant and often severe vision loss at an early age.
      Comprehensive analysis of the genetic mutations and phenotypic correlations in
      LCA patients has allowed for significant improvements in understanding molecular
      pathways of photoreceptor degeneration and dysfunction. The purpose of this
      article is to review the literature on the subject of retinal gene therapy for
      LCA, including historical descriptions, preclinical animal studies, and human
      clinical trials. METHODS: A literature search of peer-reviewed and indexed
      publications from 1996-2011 using the PubMed search engine was performed. Key
      terms included "Leber congenital amaurosis", LCA, RPE65, "cone-rod dystrophy",
      "gene therapy", and "human trials" in various combinations. Seminal articles
      prior to 1996 were selected from primary sources and reviews from the initial
      search. Articles were chosen based on pertinence to clinical, genetic, and
      therapeutic topics reviewed in this manuscript. Fundus photographs from LCA
      patients were obtained retrospectively from the clinical practice of one of the
      authors (R.A.S). RESULTS: Herein, we reviewed the literature on LCA as a genetic
      disease, the results of human gene therapy trials to date, and possible future
      directions towards treating inherited retinal diseases at the genetic level.
      Original descriptions of LCA by Theodor Leber and subsequent research demonstrate
      the severity of this disease with early-onset blindness. Discoveries of the
      causative heritable mutations revealed genes and protein products involved in
      photoreceptor development and visual transduction. Animal models have provided a
      means to test novel therapeutic strategies, namely gene therapy. Stemming from
      these experiments, three independent clinical trials tested the safety of
      subretinal delivery of viral gene therapy to patients with mutations in the RPE65
      gene. More recently, efficacy studies have been conducted with encouraging
      results. CONCLUSIONS: Initial safety studies indicated promising results of
      subretinal delivery of viral vector with subclinical immunologic or surgical
      sequelae. Overall, these initial studies demonstrate that viral vector gene
      therapy results are very promising, safe, and effective. Future studies measuring
      potential improvement in photoreceptor function may rely on recent advances in
      retinal imaging and electrophysiologic testing.

PMID- 22644096
TI  - Glaucoma in penetrating keratoplasty: risk factors, management and outcome.
AB  - INTRODUCTION: Glaucoma is a leading cause for graft failure. This retrospective
      study analyzes the risk factors, graft status, and treatment modalities in
      patients with post-penetrating keratoplasty glaucoma. METHODS: A retrospective
      analysis of case records of 1,848 penetrating keratoplasties carried out between
      2000 and 2005 was performed. A total of 160 patients (160 eyes) with post
      penetrating keratoplasty glaucoma were included; 112 cases were primary grafts,
      48 repeated grafts. The assessment included the pre-operative history of corneal
      disease and glaucoma, the lens status, and the anesthesiological techniques.
      Furthermore, the response to anti-glaucoma treatment, graft failure, and
      endothelial cell loss was evaluated. RESULTS: The incidence of post-penetrating
      keratoplasty glaucoma was 8.7 % (160/1,848). Preoperative glaucoma was the most
      important risk factor (62/160). Half of the patients (81 patients) responded to
      medical therapy (51 %) and the other half of patients (79 patients) to surgical
      therapy (49 %); of the latter, filtering surgery were performed in 16 %,
      cyclodestructive procedures in 66 % and both in 16 %. One patient received a
      glaucoma implant and cyclodestructive procedures (1 %). After 24 months, clear
      grafts were achieved in 94 eyes (59 %). Visual acuity after 24 months of 20/200
      (logMAR 1.0) or better was achieved in 77 eyes (46 %) and of 20/50 (logMAR 0.4)
      in 33 eyes (21 %). CONCLUSIONS: Careful and ongoing observation of IOP,
      especially in the first year after PK, is recommended for patients after
      penetrating keratoplasty and prompt treatment of IOP elevation when indicated.
      Early filtering surgery with a better outcome than other surgery procedures
      should be preferred if medical treatment is not sufficient. Despite anti-glaucoma
      therapy, good visual outcome can remain beyond expectations despite a clear
      graft. While there is a potential option for graft exchange, damage to the optic
      nerve from end-stage glaucoma leads immutably to visual loss.

PMID- 22644102
TI  - Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and
      predicts disease outcome in patients with dermatomyositis and rapidly progressive
      interstitial lung disease.
AB  - OBJECTIVES: We examined the relationship between disease activity and anti-CADM
      140/MDA5 titer measured by enzyme-linked immunosorbent assay (ELISA). METHODS:
      Sera from 63 patients with dermatomyositis (DM) [46 classic DM, 17 clinically
      amyopathic DM (CADM)] were screened for autoantibody using immunoprecipitation
      assay. Anti-CADM-140/MDA5-positive sera were examined for their titer by anti
      CADM-140/MDA5 ELISA. Potential associations between anti-CADM-140/MDA5 titer and
      clinical course or outcome were analyzed. RESULTS: Sera from 14 patients with DM
      (2 classic DM, 12 CADM) had anti-CADM-140/MDA5. Of ten patients with DM and
      rapidly progressive interstitial lung disease (RP-ILD), the mean titer of anti
      CADM-140/MDA5 before treatment was significantly lower in patients who responded
      to therapy and survived (responder group, n = 4) than in those who did not
      respond and died (nonresponder group, n = 6) (110.3 vs. 356.9, P = 0.019). In the
      responder group, the mean titer of anti-CADM-140/MDA5 significantly decreased
      down to below the cutoff level after treatment (n = 3, 113.4 vs. 1.6, P = 0.033),
      whereas that of the nonresponder group did not decrease sufficiently and
      sustained high level (n = 4, 372.5 vs. 198.4, P = 0.31). CONCLUSIONS: These
      results emphasize the clinical importance of anti-CADM-140/MDA5 antibody levels
      to predict outcomes of RP-ILD as well as to monitor disease activity in patients
      with DM and RP-ILD.

PMID- 22644097
TI  - Attentional bias in problem gambling: a systematic review.
AB  - Attentional bias has been the subject of extensive empirical investigation in
      connection with chemical addictions, and it has been demonstrated in users of
      several different substances. The findings show that substance users seem to
      notice and attend to substance-related stimuli more readily than non-substance
      related stimuli. Less is known, however, about attentional bias in pathological
      gambling. This systematic review investigates the existing empirical evidence on
      attentional bias in problem and pathological gamblers. Eleven studies were
      identified and evaluated following a literature search. Key findings are that
      problem and pathological gamblers seem to exhibit attentional bias toward
      gambling-related stimuli across different measuring paradigms, although some
      negative findings were reported. Recommendations aimed at improving research on
      this topic include better validation of measures, the inclusion of manipulations
      of craving level, and adding variations in gambling severity as a variable, as
      well as gambling preference. Research on therapeutic procedures aimed at reducing
      attentional bias is also recommended. 

PMID- 22644104
TI  - Optical CT scanner for in-air readout of gels for external radiation beam 3D
      dosimetry.
AB  - Optical CT scanners for a 3D readout of externally irradiated radiosensitive
      hydrogels currently require the use of a refractive index (RI) matching liquid
      bath to obtain suitable optical ray paths through the gel sample to the detector.
      The requirement for a RI matching liquid bath has been negated by the design of a
      plastic cylindrical gel container that provides parallel beam geometry through
      the gel sample for the majority of the projection. The design method can be used
      for various hydrogels. Preliminary test results for the prototype laser beam
      scanner with ferrous xylenol-orange gel show geometric distortion of 0.2 mm
      maximum, spatial resolution limited to beam spot size of about 0.4 mm and 0.8%
      noise (1 SD) for a uniform irradiation. Reconstruction of a star pattern
      irradiated through the cylinder walls demonstrates the suitability for external
      beam applications. The extremely simple and cost-effective construction of this
      optical CT scanner, together with the simplicity of scanning gel samples without
      RI matching fluid increases the feasibility of using 3D gel dosimetry for
      clinical external beam dose verifications.

PMID- 22644105
TI  - Functional investigation of beta-adrenoceptors in human isolated detrusor
      focusing on the novel selective beta3-adrenoceptor agonist KUC-7322.
AB  - This study aimed to characterize the beta-adrenoceptor (beta-AR) subtype
      mediating relaxation of isolated human bladder strips and to explore relaxation
      by the novel beta3-AR-selective agonist KUC-7322 for its relaxant effect on the
      human isolated detrusor and for its effect on the carbachol (CCh)-induced
      contractile response. In two parallel studies, relaxation of isolated human
      bladder strips was tested for the beta-AR agonists isoproterenol, clenbuterol,
      BRL 37344, and KUC-7322. For the isoproterenol and KUC-7322 responses, antagonism
      by CGP 20712A, ICI 118551, and SR59230A was determined. The potency and efficacy
      of the reference agonists for detrusor relaxation was in line with their known
      beta3-AR activity. KUC-7322 relative to isoproterenol was a full agonist with a
      pEC(50) of 5.95 +/- 0.09 and 5.92 +/- 0.11 in the two studies. SR59230A exhibited
      antagonism of the expected potency against isoproterenol (apparent pK (B) 7.2)
      but not against KUC-7322. Neither isoproterenol nor KUC-7322 nor forskolin
      significantly attenuated CCh-induced contraction. These results suggest that KUC
      7322 displays full agonistic activity in relaxing the human detrusor without
      inhibiting the contraction induced by cholinergic stimulation. These
      characteristics, if proven in vivo, may be beneficial for the treatment of
      overactive bladder, as increased bladder capacity with a negligible effect on
      voiding contractions may be anticipated.

PMID- 22644106
TI  - Inhibition of macrophage migration by C. botulinum exoenzyme C3.
AB  - C3-like exoenzymes are produced by various microorganism including Clostridium
      botulinum (C3bot), Bacillus cereus and Staphylococcus aureus. C3bot is the
      prototype of C3-like exoenzymes that specifically ADP-ribosylates and thereby
      inactivates Rho(A/B/C). C3-like exoenzymes are not yet regarded as virulence
      factors, as the lack of cell entry domains results in a poor accessibility of the
      C3-like exoenzymes to cells. In this study, the sensitivity of various cell lines
      to C3bot has been reinvestigated. Primary monocytes as well as cultured
      macrophage-like cells including J774A.1 cells and RAW macrophages exhibit a
      tenfold higher sensitivity to C3bot than fibroblasts and epithelial cells. RhoA
      ADP-ribosylation by C3bot resulted in the formation of pronounced bipolar
      protrusions based on defective tail retraction. The formation of bipolar
      protrusion resulted in inhibited macrophage migration. These findings suggested
      that macrophages appear to be target cells of C3bot. Migration of macrophage is a
      prerequiste for their recruitment to the site of pathogen invasion or tissue
      damage. Inhibition of macrophage migration likely preserves the survival of C3
      producing microorganisms. The observations of this study reinforce the paradigm
      of a role of C3-like exoenzymes as virulence factors.

PMID- 22644107
TI  - Intravenous immunoglobulin preparation attenuates LPS-induced production of pro
      inflammatory cytokines in human monocytic cells by modulating TLR4-mediated
      signaling pathways.
AB  - Intravenous immunoglobulin (IVIG) has been used for the treatment of inflammatory
      and autoimmune diseases. The ability to modulate cytokine production has been
      formerly described as one of the mechanisms of its action. This study aimed to
      investigate the effect of IVIG on the production of pro-inflammatory cytokines in
      lipopolysaccharide (LPS)-stimulated monocytic cells. Peripheral blood mononuclear
      cells (PBMCs) or THP-1 cells treated with phorbol myristate acetate (PMA) were
      stimulated with LPS. The protein levels of pro-inflammatory cytokines [tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6, and high-mobility group box 1
      (HMGB1)] in the culture supernatants were determined using appropriate enzyme
      linked immunosorbent assay kits. The mRNA of TNF-alpha was determined by reverse
      transcription-polymerase chain reaction. The phosphorylation of nuclear factor
      kappa B (NF-kappaB) and the mitogen-activated protein kinases was examined by
      Western blot analyses. IVIG suppressed the production of pro-inflammatory
      cytokines such as TNF-alpha and IL-6 in LPS-stimulated PBMCs. Furthermore, IVIG
      inhibited TNF-alpha, IL-6, and HMGB1 production from LPS-stimulated THP-1 cells
      treated with PMA. In addition, Fc fragment prepared from the IVIG inhibited
      production of these cytokines from the cells to the same degree as IVIG, whereas
      Fab and F(ab')(2) fragments inhibited this only partially. We showed that IVIG
      and Fc fragments suppressed LPS-induced signal transduction pathways involving
      phosphorylation of NF-kappaB, p38, and c-Jun N-terminal kinase (JNK). Taken
      together, our results suggest that IVIG attenuates LPS-induced cytokine
      production predominantly mediated by its Fc region. The activity might be
      regulated by inhibiting NF-kappaB, p38, and JNK pathways in human monocytic
      cells.

PMID- 22644109
TI  - Menopausal hormone therapy and risks of colorectal adenomas and cancers in the
      French E3N prospective cohort: true associations or bias?
AB  - Menopausal hormone therapy (MHT) use has been quite consistently associated with
      a decreased colorectal cancer risk; however, data regarding adenomas, types of
      MHT, or tumour site are limited. We investigated associations between MHT use and
      colorectal adenoma and cancer risks within the prospective E3N cohort study. In
      the adenoma study, we analyzed the 13,402 postmenopausal women who underwent a
      colonoscopy during follow-up (1993-2002), including 1,109 who were diagnosed a
      first colorectal adenoma. In the cancer study, 525 out of 77,375 postmenopausal
      women developed a colorectal cancer as the first malignant tumour during follow
      up (1992-2008). Ever use of MHT was not significantly associated with colorectal
      adenoma risk [Hazard Ratio (HR) = 1.13, 95 % Confidence Interval (CI) = 0.99,
      1.29], nor with colorectal cancer risk (HR = 0.86, 95 % CI = 0.71, 1.04).
      However, ever use of estrogens alone was associated with risks of colorectal
      adenoma and cancer in opposite directions (HR = 1.22, 95 % CI = 1.05, 1.41 and HR
      = 0.72, 95 % CI = 0.56, 0.94 respectively). Associations were strongest for non
      advanced, and for left colon adenomas. Duration, recency of use, type of
      progestagen or route of estrogen administration were not associated with
      colorectal tumour risk, nor was the use of estrogen-progestagen MHT. The
      association between estrogens alone and colorectal cancer risk was only observed
      in women with previous colonoscopy(ies), but the P value of the interaction test
      between estrogens alone use and history of colonoscopy was 0.06. Our data suggest
      a complex relationship between MHT use, colorectal tumour risk and screening
      strategies, which deserves further investigations in other settings.

PMID- 22644108
TI  - Estimating the alcohol-breast cancer association: a comparison of diet diaries,
      FFQs and combined measurements.
AB  - The alcohol-breast cancer association has been established using alcohol intake
      measurements from Food Frequency Questionnaires (FFQ). For some nutrients diet
      diary measurements are more highly correlated with true intake compared with FFQ
      measurements, but it is unknown whether this is true for alcohol. A case-control
      study (656 breast cancer cases, 1905 matched controls) was sampled from four
      cohorts in the UK Dietary Cohort Consortium. Alcohol intake was measured
      prospectively using FFQs and 4- or 7-day diet diaries. Both relied on fixed
      portion sizes allocated to given beverage types, but those used to obtain FFQ
      measurements were lower. FFQ measurements were therefore on average lower and to
      enable fair comparison the FFQ was "calibrated" using diet diary portion sizes.
      Diet diaries gave more zero measurements, demonstrating the challenge of
      distinguishing never-from episodic-consumers using short term instruments. To use
      all information, two combined measurements were calculated. The first is an
      average of the two measurements with special treatment of zeros. The second is
      the expected true intake given both measurements, calculated using a measurement
      error model. After confounder adjustment the odds ratio (OR) per 10 g/day of
      alcohol intake was 1.05 (95 % CI 0.98, 1.13) using diet diaries, and 1.13 (1.02,
      1.24) using FFQs. The calibrated FFQ measurement and combined measurements 1 and
      2 gave ORs 1.10 (1.03, 1.18), 1.09 (1.01, 1.18), 1.09 (0.99,1.20), respectively.
      The association was modified by HRT use, being stronger among users versus non
      users. In summary, using an alcohol measurement from a diet diary at one time
      point gave attenuated associations compared with FFQ.

PMID- 22644110
TI  - Body mass index and mortality in an ethnically diverse population: the
      Multiethnic Cohort Study.
AB  - Body mass index (BMI) has been strongly related to overall mortality, but the
      consistency of this association across diverse ethnic groups and the effects of
      early adult BMI versus BMI in later adulthood have not been adequately studied. A
      prospective analysis was performed using data from 183,211 adults aged 45-75 who
      enrolled the population-based Multiethnic Cohort Study by completing a
      questionnaire that included self-reported weight and height information in 1993
      1996. Participants were African Americans, Native Hawaiians, Japanese Americans,
      Latinos, and whites living in Hawaii and California. During an average 12.5 years
      of follow-up, 35,664 deaths were identified. To control for confounding caused by
      conditions that lead to weight loss and mortality, we excluded participants with
      a history of cancer or heart disease, who ever smoked, and who died within the
      first 3 years of follow-up. An increased risk of mortality was observed in
      participants with a BMI >= 27.5 in both men and women compared with the reference
      category of BMI 23.0-24.9; a BMI >= 35.0 carried a greater risk of mortality in
      men than in women. Although the findings were generally similar across ethnic
      groups, the association of higher BMI with mortality in Latino men appeared to be
      weaker than in the other groups. A BMI of 25.0-34.9 at age 21 showed a stronger
      positive association, with no further increase in risk for a BMI >= 35.0, than
      did BMI in later adulthood. These results indicate that the association of BMI
      with mortality is generally consistent across sex and ethnic groups, with some
      variation in the strength of the effect. Most notably, the effect of overweight
      in young adulthood appears to be much stronger than that of overweight in later
      adulthood on mortality in later life. This emphasizes the importance of weight
      management in childhood and adolescence.

PMID- 22644111
TI  - Proteomics pipeline for biomarker discovery of laser capture microdissected
      breast cancer tissue.
AB  - Mass spectrometry (MS)-based label-free proteomics offers an unbiased approach to
      screen biomarkers related to disease progression and therapy-resistance of breast
      cancer on the global scale. However, multi-step sample preparation can introduce
      large variation in generated data, while inappropriate statistical methods will
      lead to false positive hits. All these issues have hampered the identification of
      reliable protein markers. A workflow, which integrates reproducible and robust
      sample preparation and data handling methods, is highly desirable in clinical
      proteomics investigations. Here we describe a label-free tissue proteomics
      pipeline, which encompasses laser capture microdissection (LCM) followed by
      nanoscale liquid chromatography and high resolution MS. This pipeline routinely
      identifies on average ~10,000 peptides corresponding to ~1,800 proteins from sub
      microgram amounts of protein extracted from ~4,000 LCM breast cancer epithelial
      cells. Highly reproducible abundance data were generated from different technical
      and biological replicates. As a proof-of-principle, comparative proteome analysis
      was performed on estrogen receptor alpha positive or negative (ER+/-) samples,
      and commonly known differentially expressed proteins related to ER expression in
      breast cancer were identified. Therefore, we show that our tissue proteomics
      pipeline is robust and applicable for the identification of breast cancer
      specific protein markers.

PMID- 22644112
TI  - Isolation of mouse mammary epithelial subpopulations: a comparison of leading
      methods.
AB  - Isolation of mammary epithelial subpopulations, including stem and progenitor
      cells, has become a standard technique in recent years. However, a number of
      methods and approaches for this have developed and the relative benefits of the
      different approaches, and the reason for their development, have not always been
      clear. Here, three of the leading laboratories working on the separation of
      mammary cell subpopulations have summarised their methods, highlighted their
      differences and similarities and also discussed the reasoning behind the
      approaches they have taken. This article will assist workers establishing mammary
      cell separation protocols in their laboratories to make informed choices about
      the methods they should use.

PMID- 22644113
TI  - Empathic-like responding by domestic dogs (Canis familiaris) to distress in
      humans: an exploratory study.
AB  - Empathy covers a range of phenomena from cognitive empathy involving
      metarepresentation to emotional contagion stemming from automatically triggered
      reflexes. An experimental protocol first used with human infants was adapted to
      investigate empathy in domestic dogs. Dogs oriented toward their owner or a
      stranger more often when the person was pretending to cry than when they were
      talking or humming. Observers, unaware of experimental hypotheses and the
      condition under which dogs were responding, more often categorized dogs'
      approaches as submissive as opposed to alert, playful or calm during the crying
      condition. When the stranger pretended to cry, rather than approaching their
      usual source of comfort, their owner, dogs sniffed, nuzzled and licked the
      stranger instead. The dogs' pattern of response was behaviorally consistent with
      an expression of empathic concern, but is most parsimoniously interpreted as
      emotional contagion coupled with a previous learning history in which they have
      been rewarded for approaching distressed human companions.

PMID- 22644114
TI  - Are head cues necessary for goats (Capra hircus) in recognising group members?
AB  - In this study, we investigated whether goats can distinguish a member of their
      own group from one belonging to a different group even when the head of the goat
      in question cannot be seen. In the experiment, a total of 45 adult female goats
      (walkers) were trained to walk along a passageway at the end of which they learnt
      to expect food (trial run). Walking down this corridor, they passed another adult
      female goat (stimulus goat) whose trunk and hind legs alone were visible. Using
      19 individuals, ten pairs of stimulus goats consisting of one goat from the
      walker's group and one from a different group were matched in terms of body size,
      constitution, colour and coat length. In addition, the stimulus goat from the
      same group as the walker had to be higher ranking than the latter to avoid being
      attacked. The walkers completed two, four or six trial runs depending on the
      number of pairs suitable for a given walker. The walker's exploratory behaviour
      (observing and sniffing at the stimulus goat) was recorded. Data from 109 trial
      runs were analysed using generalised linear mixed-effects models with crossed
      random effects. On average, the walker spent a total of 8.7 s exploring the
      stimulus goat visually and olfactorily if the latter was from a different group
      and only about half as long (4.2 s) if it was from her own group. In particular,
      the time a walker spent observing a stimulus goat whilst approaching the latter
      was significantly longer if the stimulus goat belonged to a different group than
      to her own (2.5 s as opposed to 1.4 s). Moreover, a stimulus goat from a
      different group was sniffed at significantly longer (4.6 s) than one from the
      same group (1.9 s). Results suggest that goats can easily discriminate between
      members of their own group and those of a different group even when the latter's
      heads are hidden. Olfactory and visual cues are probably important for
      identifying group members.

PMID- 22644115
TI  - Problem solving in great apes (Pan paniscus, Pan troglodytes, Gorilla gorilla,
      and Pongo abelii): the effect of visual feedback.
AB  - What kind of information animals use when solving problems is a controversial
      topic. Previous research suggests that, in some situations, great apes prefer to
      use causally relevant cues over arbitrary ones. To further examine to what extent
      great apes are able to use information about causal relations, we presented three
      different puzzle box problems to the four nonhuman great ape species. Of primary
      interest here was a comparison between one group of apes that received visual
      access to the functional mechanisms of the puzzle boxes and one group that did
      not. Apes' performance in the first two, less complex puzzle boxes revealed that
      they are able to solve such problems by means of trial-and-error learning,
      requiring no information about the causal structure of the problem. However,
      visual inspection of the functional mechanisms of the puzzle boxes reduced the
      amount of time needed to solve the problems. In the case of the most complex
      problem, which required the use of a crank, visual feedback about what happened
      when the handle of the crank was turned was necessary for the apes to solve the
      task. Once the solution was acquired, however, visual feedback was no longer
      required. We conclude that visual feedback about the consequences of their
      actions helps great apes to solve complex problems. As the crank task matches the
      basic requirements of vertical string pulling in birds, the present results are
      discussed in light of recent findings with corvids.

PMID- 22644119
TI  - SiPM-PET with a short optical fiber bundle for simultaneous PET-MR imaging.
AB  - For positron emission tomography (PET) inserts to magnetic resonance imaging
      (MRI) applications, optical fibers have been used for some time to transfer
      scintillation photons to photomultiplier tubes positioned outside the fringe
      magnetic field. We previously proposed a novel utilization of an optical fiber
      for good radio frequency (RF) transmission from body coils to an imaging object.
      Optical fiber bundles between silicon photomultipliers (SiPM) and scintillation
      crystals provide an increased spacing between RF-shielded electronics boxes,
      facilitating RF passage from the body RF coils to imaging objects. In this paper,
      we present test results of a SiPM-PET system with a short optical fiber bundle
      for simultaneous PET-MR imaging. We built the SiPM-PET system which consisted of
      12 SiPM-PET modules; each module was assembled with a lutetium yttrium
      oxyorthosilicatecrystal block, a 31 mm optical fiber bundle, a Hamamatsu multi
      pixel photon counter S11064-050P and a signal processing box shielded with
      copper. The SiPM-PET system, with a face-to-face distance of 71 mm, was placed
      inside a 3 T MRI. A small surface coil placed inside the SiPM-PET system was used
      to receive the signal from phantoms while the body RF coil transmitted the RF
      pulses. The SiPM-PET system showed little performance degradation during the
      simultaneous PET-MR imaging and it caused no significant degradation of MR images
      with turbo spin echo (TSE), gradient echo or 3D spoiled gradient recalled
      sequences. Echo planar imaging MR images with and without the SiPM-PET inside the
      MR scanner were significantly worse than the images obtained with the TSE
      sequence.

PMID- 22644120
TI  - Sources and distribution of polycyclic aromatic hydrocarbons in street dust from
      the Chang-Zhu-Tan Region, Hunan, China.
AB  - Street dusts collected from 20 locations in the Chang-Zhu-Tan (Changsha, Zhuzhou,
      and Xiangtan) region, Hunan, China, in May to July 2006, were investigated for
      sources of polycylic aromatic hydrocarbons (PAHs). The individual PAH
      concentrations were in the range of 10-4316 ng g(-1), and ?PAHs(16) levels were
      in the range of 3,515-24,488 ng g(-1), with a mean of 8,760 ng g(-1). The high
      molecular-weight PAHs (four to six rings), ranging from 47.51 to 82.11 %, with a
      mean of 74.79 %, were the dominant PAH compounds in almost all of the dusts. The
      isomer ratios suggested a rather uniform mixture of coal combustion and petroleum
      PAH sources. Factor analysis and multiple linear regression analysis indicate
      that the main sources of the 16 PAHs were coal combustion/vehicle exhaust,
      coking/petroleum, and plant combustion, with contribution rates of 50.9, 35.01,
      and 14.08, respectively. The spatial distributions of PAH concentrations were
      significantly related to the distribution of industries, traffic circulation, and
      farmland in this region.

PMID- 22644121
TI  - Effect of fishing vessels on trace metal contamination in sediments of three
      harbors along Iranian Oman Sea coast.
AB  - In this study, the levels of natural and anthropogenic metal contamination
      (aluminum (Al), iron (Fe), manganese (Mn), arsenic (As), cadmium (Cd), chromium
      (Cr), copper (Cu), nickel (Ni), lead (Pb), and zinc (Zn)) in surface sediments of
      three harbors along the Iranian coast of Gulf of Oman were examined and reported
      for the first time. Effect of grain size, mineralogy, normalization technique
      using Fe concentrations, and different sediment quality guidelines were
      discussed. Data from the harbors were compared with other harbors worldwide.
      Sediments inside the harbors are characterized by moderate and high levels of
      pollution by trace metals Cu (12-287 MUg/g), Pb (11-1,780 MUg/g), Zn (38-547
      MUg/g), Cr (70-2,370 MUg/g), and Ni (31-116 MUg/g). However, As and Cd did not
      show considerable pollution inside and outside the harbors. Considering that
      there is no industrial activity around the study harbors, the major sources of
      contamination in the harbors are repairing, fueling, greasing, and painting of
      fishing ships and boats. Mineralogy of sediments in the study area as well as
      trace metal concentration in reference samples taken from onshore geological
      units confirmed that natural inputs of Cd, Cu, Pb, and Zn in the harbors are very
      low while most of Ni and Cr contamination in the study area comes from erosion of
      ophiolitic melange units at the North of Makran mountains.

PMID- 22644122
TI  - Assessment of metal pollution in urban road dusts from selected highways of the
      Greater Toronto Area in Canada.
AB  - Over the last several decades, there has been increased attention on the heavy
      metal contamination associated with highways because of the associated health
      hazards and risks. Here, the results are reported of an analysis of the content
      of metals in roadside dust samples of selected major highways in the Greater
      Toronto Area of Ontario, Canada. The metals analysed are lead (Pb), zinc (Zn),
      cadmium (Cd), nickel (Ni), chromium (Cr), copper (Cu), manganese (Mn), calcium
      (Ca), potassium (K), magnesium (Mg) and iron (Fe). In the samples collected, the
      recorded mean concentrations (in parts per million) are as follows: Cd (0.51), Cu
      (162), Fe (40,052), Cr (197.9), K (9647.6), Mg (577.4), Ca (102,349), Zn (200.3),
      Mn (1202.2), Pb (182.8) and Ni (58.8). The mean concentrations for the analysed
      samples in the study area are almost all higher than the average natural
      background values for the corresponding metals. The geo-accumulation index of
      these metals in the roadside dust under study indicates that they are not
      contaminated with Cr, Mn and Ca; moderately contaminate with Cd and K; strongly
      contaminated with Fe and Mg; strongly to extremely contaminated with Ni and Pb;
      and extremely contaminated with Cu and Zn. The pollution load index (PLI) is used
      to relate pollution to highway conditions, and the results show that PLI values
      are slightly low at different samples collected from Highways 401 and 404 and
      high in many samples collected from Highway 400 and the Don Valley Parkway.
      Highway 400 exhibits the highest PLI values.

PMID- 22644123
TI  - Time course of organochlorine pesticides and polychlorinated biphenyls in breast
      feeding mothers throughout the first 10 months of lactation in Tunisia.
AB  - Organochorine (OCs) residues were measured in human breast milk samples from four
      Tunisian women. Month-mix samples composed of weekly collected breast milk
      samples were analyzed over the lactation period between 3 days after delivery and
      10 months post-partum. The concentrations of dichlorodiphenytrichloroethane and
      its metabolites (DDTs), hexachlorobenzene (HCB), hexachlorocyclohexane isomers
      (HCHs), dieldrin, and 20 polychlorinated biphenyl congeners (PCBs) were
      determined by gas chromatography with electron capture detection. The variation
      of OC residue levels in human milk was investigated for each woman individually.
      The average p,p'-DDE and p,p'-DDT concentrations declined from 661- and 438-ng g(
      1) fat basis at day 3 to 77- and 106-ng g(-1) fat basis after 8 months,
      respectively. No essential changes in HCB, HCHs, dieldrin, and total PCBs
      concentrations in human breast milk occurred over the lactation periods
      investigated; the concentrations remained either relatively constant or show no
      significant weak decrease.

PMID- 22644124
TI  - Load estimation and source apportionment of nonpoint source nitrogen and
      phosphorus based on integrated application of SLURP model, ECM, and RUSLE: a case
      study in the Jinjiang River, China.
AB  - The nonpoint source (NPS) pollution is difficult to manage and control due to its
      complicated generation and formation. Load estimation and source apportionment
      are an important and necessary process for efficient NPS control. Here, an
      integrated application of semi-distributed land use-based runoff process (SLURP)
      model, export coefficients model (ECM), and revise universal soil loss equation
      (RUSLE) for the load estimation and source apportionment of nitrogen and
      phosphorus was proposed. The Jinjiang River (China) was chosen for the evaluation
      of the method proposed here. The chosen watershed was divided into 27 subbasins.
      After which, the SLURP model was used to calculate land use runoff and to
      estimate loads of dissolved nitrogen and phosphorus, and ECM was applied to
      estimate dissolved loads from livestock and rural domestic sewage. Next, the
      RUSLE was employed for load estimation of adsorbed nitrogen and phosphorus. The
      results showed that the 12,029.06 t a(-1) pollution loads of total NPS nitrogen
      (TN) mainly originated from dissolved nitrogen (96.24 %). The major sources of TN
      were land use runoff, which accounted for 45.97 % of the total, followed by
      livestock (32.43 %) and rural domestic sewage (17.83 %). For total NPS
      phosphorous (TP), its pollution loads were 570.82 t a(-1) and made up of
      dissolved and adsorbed phosphorous with 66.29 and 33.71 % respectively. Soil
      erosion, land use runoff, rural domestic sewage, and livestock were the main
      sources of phosphorus with contribution ratios of 33.71, 45.73, 14.32, and 6.24 %
      respectively. Therefore, land use runoff, livestock, and soil erosion were
      identified as the main pollution sources to influence loads of NPS nitrogen and
      phosphorus in the Jinjiang River and should be controlled first. The method
      developed here provided a helpful guideline for conducting NPS pollution
      management in similar watershed.

PMID- 22644125
TI  - Assessing implications of land use and land cover changes in forest ecosystems of
      NE Turkey.
AB  - Monitoring land use and land cover change (LUCC) and understanding forest cover
      dynamics is extremely important in sustainable development and management of
      forest ecosystems. This study analyzed the spatial and temporal pattern of LUCC
      in the Yalnizcam and Ugurlu forest planning units which are located in the
      northeast corner of Turkey. The investigation also evaluates the temporal changes
      of the spatial structure of forest conditions through the spatial analysis of
      forest-cover type maps from 1972 and 2005 using geographical information systems
      and FRAGSTATS(TM). As an overall change between 1972 and 2005, there was a net
      increase of 1,823 ha in forested areas, and cumulative forest improvement
      accounted for 2.06 %. In terms of spatial configuration, the landscape structure
      in the study area changed substantially over the 33-year study period, resulting
      in fragmentation of the landscape as indicated by large patch numbers and smaller
      mean patch sizes, owing to heavy grazing, illegal cutting, and uncontrolled stand
      treatments.

PMID- 22644126
TI  - Estimating reference nutrient criteria for Maryland ecoregions.
AB  - Management of stream nutrients is becoming increasingly important in order to
      protect both water quality and aquatic resources throughout the USA. Using an
      extensive water quality database from the long-term Maryland Biological Stream
      Survey (MBSS), we describe nutrient relationships to landscape characteristics as
      total nitrogen (TN) and total phosphorus (TP) of small-order, non-tidal streams
      in USEPA L2 and L3 ecoregions in Maryland and by MBSS stream order at the L2 and
      L3 ecoregion levels. To protect stream ecosystem integrity, preliminary reference
      nutrient estimates (TN and TP) as percentiles (25th of all stream reaches and
      75th of stream reference reaches) for the six Maryland L3 ecoregions are: Blue
      Ridge TN 0.29 and 0.64 mg/L, TP 0.0065 and 0.0090 mg/L; Central Appalachians TN
      0.40 and 1.0 mg/L, TP 0.0060 and 0.015 mg/L; Middle Atlantic Coastal Plains TN
      0.93 and 2.5 mg/L, TP 0.094 and 0.065 mg/L; Northern Piedmont TN 1.6 and 1.8
      mg/L, TP 0.010 and 0.015 mg/L; Ridge and Valley TN 0.40 and 0.98 mg/L, TP 0.0063
      and 0.012 mg/L; and Southeastern Plains TN 0.33 and 0.82 mg/L, TP 0.016 and 0.042
      mg/L. High levels of both TN and TP are present in many streams found in non
      tidal watersheds associated with all Maryland ecoregions, but are especially
      elevated in the Northern Piedmont and Middle Atlantic Coastal Plain ecoregions,
      with the latter second-order streams (average TN > 2.9 mg/L) significantly higher
      than all other ecoregion-order combinations. Across all six ecoregions, mean
      nutrient loading for both TN and TP was generally equivalent in first-order
      streams to nutrient concentrations seen in both second- and third-order streams,
      indicating a definite need to increase efforts in preventing nutrients from
      entering first-order streams. Small-order stream nutrient levels are the drivers
      for subsequent TN and TP inputs into the upper freshwater tidal reaches of the
      Chesapeake Bay, resulting in a potential risk for altered estuarine ecosystems.

PMID- 22644127
TI  - Altruism in time: social temporal discounting differentiates smokers from problem
      drinkers.
AB  - RATIONALE: Recent studies on reinforcer valuation in social situations have
      informed research on mental illness. Social temporal discounting may be a way to
      examine effects of social context on the devaluation of delayed reinforcers. In
      prior research with non-drug-using groups, we demonstrated that individuals
      discount delayed rewards less rapidly (i.e., value the future more) for a group
      of which they are a member than they do for themselves alone. OBJECTIVES: The
      current study examined how cigarette smoking and level of alcohol use relate to
      rates of delay and social temporal discounting. METHODS: In this study, we used
      crowd-sourcing technology to contact a large number of individuals (N = 796).
      Some of these individuals were hazardous-to-harmful drinkers (n = 269), whereas
      others were non-problem drinkers (n = 523); some were smokers (n = 182), whereas
      others were nonsmokers (n = 614). Delay discounting questionnaires for individual
      rewards (me now, me later) and for group rewards (we now, we later; me now, we
      later) were used to measure individuals' discounting rates across various social
      contexts. RESULTS: Our analyses found that smokers discounted delayed rewards
      more rapidly than controls under all conditions. However, hazardous-to-harmful
      drinkers discounted delayed rewards significantly more rapidly than the non
      problem drinkers under the individual condition, but not under the social
      conditions. CONCLUSIONS: This finding suggests that the use of different abused
      drugs may be associated with excessive discounting in the individual condition
      and has selective effects when discounting for a group in the social conditions.

PMID- 22644128
TI  - Reduced activity at the 5-HT(2C) receptor enhances reversal learning by
      decreasing the influence of previously non-rewarded associations.
AB  - RATIONALE: Reversal learning deficits are a feature of many human
      psychopathologies and their associated animal models and have recently been shown
      to involve the 5-HT(2C) receptor (5-HT(2C)R). Successful reversal learning can be
      reduced to two dissociable cognitive mechanisms, to dissipate associations of
      previous positive (opposed by perseverance) and negative (opposed by learned non
      reward) valence. OBJECTIVES: This study aims to explore the effect of reducing
      activity at the 5-HT(2C)R on the cognitive mechanisms underlying spatial reversal
      learning in the mouse. METHODS: Experiment 1 used the 5-HT(2C)R antagonist
      SB242084 (0.5 mg/kg) in a between-groups serial design, experiment 2 used 5
      HT(2C)R KO mice in a repeated measures design. Animals initially learned to
      discriminate between two lit nosepoke holes. This was followed by three
      conditions; (1) full reversal, where contingencies reversed; (2) perseverance,
      where the previous CS+ became CS- and the previous CS- was replaced by a novel
      CS+; (3) learned non-reward, where the previous CS- became CS+ and the previous
      CS+ was replaced by a novel CS-. RESULTS: SB242084 treated and 5-HT(2C)R KO mice
      showed enhanced reversal learning seen as a decrease in trials, correct
      responses, and omissions to criterion in the full reversal condition. Similar
      effects were observed in the learned non-reward condition but SB242084 treated
      and 5-HT(2C)R KO mice did not differ from controls in the perseverance condition.
      SB242084 treated, but not 5-HT(2C)R KO mice, showed decreases in all latency
      indices in every condition. CONCLUSION: Reducing activity at the 5-HT(2C)R
      facilitates reversal learning in the mouse by reducing the influence of
      previously non-rewarded associations.

PMID- 22644130
TI  - Designing patient-centered personal health records (PHRs): health care
      professionals' perspective on patient-generated data.
AB  - Currently, patients not only want access to various medical records their health
      care providers keep about them, but they also are willing to become active
      participants in managing their own health information and the health information
      of the ones they care for. Personal health records were developed to help fulfill
      this need. Health care professionals are instrumental in the successful adoption
      of PHRs. Nevertheless, a full understanding of different health care
      practitioners' views of PHRs, including how PHRs could fit into the existing
      health care system, is lacking. The purpose of this exploratory study is to
      investigate PHRs from the perspective of health care professionals. Twenty-one
      practitioners with 10 different specialties were interviewed. The results suggest
      that although PHRs were still a novel concept to the study participants, a
      majority of them did value information provided by patients and would recommend
      that patients keep such records. Participants with different specialties tended
      to look for different types of information to be included in PHRs, and wished the
      information to be presented in ways that supported their work, as well as
      supported knowledge discovery. The participants also expressed a need to share
      patient information, but had various concerns about sharing. The implications of
      the results of the study in regard to the design of future PHR systems are
      discussed.

PMID- 22644131
TI  - Determinants of the severity of comorbid migraine in multiple sclerosis.
AB  - A high co-morbidity between multiple sclerosis (MS) and migraine has been
      reported, especially in young female patients affected by a relapsing-remitting
      (RR) course of MS. In this study, we aimed to elucidate the determinants of the
      severity of comorbid migraine in MS. Demographic, clinical and psychometric
      variables were collected from a cohort of 205 RR-MS patients regularly attending
      to an Italian outpatient MS Centre. Of them, 102 (49.8 %) were diagnosed as
      affected by comorbid migraine. About one-third of MS patients with comorbid
      migraine have asked the attending neurologist a specific anti-migraine treatment.
      Despite this, only few MS patients (10.8 %) reported a prior use of prophylactic
      drugs, and even fewer (2.9 %) took triptans as pain killers; these proportions
      were significantly lower when compared with those of a control group of 63
      migraineurs subjects without MS (p < 0.0001 for both comparison). Factors
      associated with a moderate or severe disability (MIDAS grades III or IV) due to
      comorbid migraine in MS patients were the depressive state (OR = 4.294; p =
      0.001), the anxiety trait (OR = 5.786; p = 0.004) and an ongoing IFNB treatment
      (OR = 2.337; p = 0.028). Likewise, depression (OR = 3.453; p = 0.048) and anxiety
      (OR = 4.582; p = 0.014) were both independent predictors for having a MIDAS
      grades of III or IV also in migraineurs subjects without MS. Investigating the
      determinants of migraine severity may allow a better management of MS patients
      with comorbid migraine. In these patients, a tailored therapeutic approach is
      warranted to improve their quality of life and reduce the burden of these two
      chronic and disabling conditions.

PMID- 22644129
TI  - Effects of noradrenergic alpha-2 receptor antagonism or noradrenergic lesions in
      the ventral bed nucleus of the stria terminalis and medial preoptic area on
      maternal care in female rats.
AB  - RATIONALE: Maternal behavior in laboratory rats requires a network of brain
      structures including the ventral bed nucleus of the stria terminalis (BSTv) and
      medial preoptic area (mPOA). Neurotransmitter systems in the BSTv and mPOA
      influencing maternal behaviors are not well understood, although norepinephrine
      is an excellent candidate because the BSTv contains the densest noradrenergic
      fiber plexus in the forebrain and norepinephrine in the mPOA is known to
      influence other female reproductive functions. OBJECTIVES: We hypothesized that
      downregulated noradrenergic activity in the BSTv and mPOA is necessary for
      mothering. METHODS: Postpartum mother-litter interactions were observed after
      BSTv infusion of yohimbine (an alpha2 autoreceptor antagonist that increases
      norepinephrine release), and after BSTv or mPOA infusion of the more selective
      alpha2 autoreceptor antagonist idazoxan. Lastly, noradrenergic input to the
      BSTv/mPOA was selectively lesioned in nulliparous rats with anti-DBH-saporin to
      determine if this would facilitate mothering. RESULTS: BSTv yohimbine almost
      abolished retrieval of pups but did not significantly affect dams' ability to
      initiate contact, lick, or nurse them. BSTv idazoxan disrupted retrieval somewhat
      less than yohimbine, but significantly reduced nursing. mPOA idazoxan impaired
      retrieval more severely than that found after BSTv infusion. Anti-DBH-saporin
      almost eliminated noradrenergic terminals in the BSTv and reduced them by over
      60% in the mPOA, but did not promote maternal responding. It also did not affect
      females' anxiety-related behavior. CONCLUSIONS: Downregulated noradrenergic
      activity in the BSTv and mPOA is necessary for postpartum maternal behavior in
      rats, but eliminating this system alone is insufficient to promote maternal
      behaviors in nulliparous females.

PMID- 22644132
TI  - Periprocedural outcome for patients with carotid stenosis treated with
      endovascular therapy: a single center evaluation.
AB  - Endovascular procedures are a less invasive revascularization strategies than
      endoarterectomy for carotid stenosis, but to date Guidelines recommend surgery
      for a major periprocedural safety. Evidences come from randomized studies where
      operator's experience in endovascular group was not considered. We
      retrospectively evaluated 524 endovascular procedures (carotid angioplasty +/-
      stenting, CAS) performed between 1996 and 2010 on 486 patients (mean age 71.3 +/-
      7.8 years) with symptomatic or asymptomatic carotid stenosis from a single
      center. We evaluated efficacy (residual stenosis <=30 % after postprocedural
      angiography) and safety [minor (TIAs or myocardial infarcts) and major (stroke or
      death) complications in the first 30 days] of procedures and correlated them with
      the increasing experience of the operator. CAS was successful in 504/524 cases
      (96.2 %); unsuccessful procedures occurred more frequently in case of angioplasty
      alone rather than angioplasty and stenting (13/61, 21.3 % vs. 7/463, 1.5 %, OR
      17.64, 95 % CI 6.69-46.06). 17/524 (3.2 %) CAS met the combined safety endpoint:
      stroke in 2.4 % and death in 0.8 %; the rate of disabling stroke/death was 1.6 %.
      Center experience was inversely related to the rate of stroke/death (R (2) =
      0.9375), passing from 5.0 % after 100 CAS to 2.8 % after 500 CAS; for disabling
      stroke/death (R(2) = 0.9386), the rate was 4 % after 100 CAS and 1.6 % after 500
      CAS. CAS is an effective and safe revascularization procedure in both symptomatic
      and asymptomatic patients, if effected in experienced centers. The use of carotid
      artery stenting than angioplasty alone and emboli protection devices can much
      more improve the previous considerations.

PMID- 22644133
TI  - Confocal observations of late-acting self-incompatibility in Theobroma cacao L.
AB  - Cocoa (Theobroma cacao) has an idiosyncratic form of late-acting self
      incompatibility that operates through the non-fusion of incompatible gametes.
      Here, we used high-resolution confocal microscopy to define fine level changes to
      the embryo sac of the strongly self-incompatible cocoa genotype SCA 24 in the
      absence of pollination, and following compatible and incompatible pollination.
      All sperm nuclei had fused with the female nuclei by 48 h following compatible
      pollinations. However, following incompatible pollinations, we observed
      divergence in the behaviour of sperm nuclei following release into the embryo
      sac. Incomplete sperm nucleus migration occurred in approximately half of the
      embryo sacs, where the sperm nuclei had so far failed to reach the female gamete
      nuclei. Sperm nuclei reached but did not fuse with the female gamete nuclei in
      the residual cases. We argue that the cellular mechanisms governing sperm nucleus
      migration to the egg nucleus and those controlling subsequent nuclear fusion are
      likely to differ and should be considered independently. Accordingly, we
      recommend that future efforts to characterise the genetic basis of LSI in cocoa
      should take care to differentiate between these two events, both of which
      contribute to failed karyogamy. Implications of these results for continuing
      efforts to gain better understanding of the genetic control of LSI in cocoa are
      discussed.

PMID- 22644134
TI  - Stability of a charged drop near a conductor wall.
AB  - The effect of conductor boundaries on the deformation and stability of a charged
      drop is presented. The motivation for such a study is the occurrence of a charged
      conductor drop near a conductor wall in experiments (Millikan-like set-up in
      studies on Rayleigh break-up) and applications (such as electrospraying, ink-jet
      printing and ion mass spectroscopy). In the present work, analytical (linear
      stability analysis (LSA)) and numerical methods (boundary element method (BEM))
      are used to understand the instability. Two kinds of boundaries are studied: a
      spherical, conducting, grounded enclosure (similar to a spherical capacitor) and
      a planar conducting wall. The LSA of a charged drop placed at the center of a
      spherical cavity shows that the Rayleigh critical charge (corresponding to the
      most unstable l = 2 Legendre mode) is reduced as the non-dimensional distance d =
      (b - a)/a decreases, where a and b are the radii of the drop and spherical
      cavity, respectively. The critical charge is independent of the assumptions of
      constant charge or constant potential conditions. The trans-critical bifurcation
      diagram, constructed using BEM, shows that the prolate shapes are subcritically
      unstable over a much wider range of charge as [Formula: see text] decreases. The
      study is then extended to the stability of a charged conductor drop near a flat
      conductor wall. Analytical theory for this case is difficult and the stability as
      well as the bifurcation diagram are constructed using BEM. Moreover, the induced
      charges in the conductor wall lead to attraction of the drop to the wall, thereby
      making it difficult to conduct a systematic analysis. The drop is therefore
      assumed to be held at its position by an external force such as the electric
      field. The case when the applied field is much smaller than the field due to
      inherent charge on the drop ((a(3)rhog)/(3epsilon(0)Psi(2)) ? 1 is considered.
      The wall breaks the fore-aft symmetry in the problem, and equilibrium,
      predominantly prolate shapes corresponding to the legendre mode, l = 2 , are
      observed. The deformation increases with increasing charge on the drop. The
      breakup of the prolate equilibrium shapes is independent of the legendre modes of
      the initial perturbations. The prolate perturbations are subcritically unstable.
      Since the equilibrium prolate shapes cannot continuously exchange instability
      with equilibrium oblate shapes, an imperfect transcritical bifurcation is
      observed. A variety of highly deformed equilibrium oblate shapes are predicted by
      the BEM calculations.

PMID- 22644135
TI  - Spontaneous formation of densely packed shear bands of rotating fragments.
AB  - Appearance of self-similar space-filling ball bearings has been suggested to
      provide the explanation for seismic gaps, shear weakness, and lack of detectable
      frictional heat formation in mature tectonic faults (shear zones). As the
      material in a shear zone fractures and grinds, it could be thought to eventually
      form a conformation that allows fragments to largely roll against each other
      without much sliding. This type of space-filling "ball bearing" can be
      constructed artificially, but so far how such delicate structures may appear
      spontaneously has remained unexplained. It is demonstrated here that first
      principles simulations of granular packing with fragmenting grains indeed display
      spontaneous formation of shear bands with fragment conformations very similar to
      those of densely packed ball bearings.

PMID- 22644136
TI  - Relaxation dynamics of poly(vinylidene fluoride) studied by dynamical mechanical
      measurements and dielectric spectroscopy.
AB  - The aim of this study is to analyze the mobility of polymer chains in
      semicrystalline poly(vinylidene fluoride) (PVDF). PVDF crystallizes from the melt
      in the alpha crystalline phase. The transformation from the alpha phase to the
      electroactive beta phase can be induced by stretching at temperatures in the
      range between 80 and 140  degrees C. The spherulitic structure of the crystalline
      phase is deformed during stretching to form fibrils oriented in the direction of
      the strain. The amorphous phase confined among the crystalline lamellae is
      distorted as well and some degree of orientation of the polymer chains is
      expected. Dynamic-mechanical and dielectric spectroscopy measurements were
      performed in PVDF films stretched to strain ratios up to 5 at temperatures
      between 80 and 140  degrees C. Dynamic-mechanical measurements were conducted
      between -60  degrees C and melting and in this temperature range the relaxation
      spectra show the main relaxation of the amorphous phase (called beta-relaxation)
      and at higher temperatures a relaxation related to crystallites motions (alpha
      (c)-relaxation). Although the mean relaxation times of the beta-relaxation are
      nearly equal in PVDF before and after crystal phase transformation, a significant
      change of shape of the relaxation spectrum proves the effect of chain distortion
      due to crystal reorganization. In stretched PVDF the elastic modulus of the
      polymer in the direction of deformation is significantly higher than in the
      transversal one, as expected by chain and crystals fibril orientation. The
      recovery of the deformation when the sample is heated is related with the
      appearance of the alpha (c)-relaxation. Dielectric spectroscopy spectrum shows
      the main relaxation of the amorphous phase and a secondary process (gamma
      relaxation) at lower temperatures. Stretching produces significant changes in the
      relaxation processes, mainly in the strength and shape of the main relaxation
      beta. The Havriliak-Negami function has been applied to analyze the dielectric
      response.

PMID- 22644137
TI  - Template free synthesis of crystallized nanoporous F-Ta2O5 spheres for effective
      photocatalytic hydrogen production.
AB  - Crystallized and fluorinated nanoporous Ta(2)O(5) spheres were prepared by a
      combination of co-precipitation and hydrothermal methods in a NH(4)F-containing
      water solution. The as-prepared porous spheres, with a pore-size of around 7 nm
      and a large specific surface area of 132 m(2) g(-1), show superior photocatalytic
      hydrogen production activity over P25 and commercial-Ta(2)O(5).

PMID- 22644142
TI  - A multidisciplinary clinic for individualizing management of patients at
      increased risk for breast and gynecologic cancer.
AB  - Increasing awareness of the hereditary component of breast and ovarian cancer has
      driven interest in creating clinics for the patient population at high risk for
      these cancers. Identifying adequate space and appropriate staff, coordinating
      multiple providers' schedules, establishing referral criteria, and addressing
      billing and reimbursement concerns are just some of the issues that are involved
      in the creation of a multidisciplinary high risk breast and ovarian cancer
      program. We provide an overview of the clinic structure at the Magee-Womens
      Hospital High Risk Breast and Ovarian Cancer Program (HRBOCP), which was created
      in 2002 due to recognition of a need for a more coordinated model of providing
      care for women at increased risk for breast and ovarian cancer. The goals of the
      HRBOCP are to evaluate women at high risk for breast and ovarian cancer and to
      organize their clinical care in a multidisciplinary setting staffed by experts in
      the field; to provide updates on new data regarding screening recommendations,
      prevention options, and risk factors pertinent to an individual's cancer risk; to
      provide ongoing support to patients and to coordinate family communication when
      appropriate; and to facilitate enrollment in appropriate research studies and
      registries.

PMID- 22644144
TI  - Multidimensional nano-HPLC coupled with tandem mass spectrometry for analyzing
      biotinylated proteins.
AB  - Multidimensional high-performance liquid chromatography (HPLC) is a key method in
      shotgun proteomics approaches for analyzing highly complex protein mixtures by
      complementary chromatographic separation principles. Here, we describe an
      integrated 3D-nano-HPLC/nano-electrospray ionization quadrupole time-of-flight
      mass spectrometry system that allows an enzymatic digestion of proteins followed
      by an enrichment and subsequent separation of the created peptide mixtures. The
      online 3D-nano-HPLC system is composed of a monolithic trypsin reactor in the
      first dimension, a monolithic affinity column with immobilized monomeric avidin
      in the second dimension, and a reversed phase C18 HPLC-Chip in the third
      dimension that is coupled to a nano-ESI-Q-TOF mass spectrometer. The 3D-LC/MS
      setup is exemplified for the identification of biotinylated proteins from a
      simple protein mixture. Additionally, we describe an online 2D-nano-HPLC/nano-ESI
      LTQ-Orbitrap-MS/MS setup for the enrichment, separation, and identification of
      cross-linked, biotinylated species from chemical cross-linking of cytochrome c
      and a calmodulin/peptide complex using a novel trifunctional cross-linker with
      two amine-reactive groups and a biotin label.

PMID- 22644143
TI  - The IL-10 promoter haplotype and cancer risk: evidence from a meta-analysis.
AB  - Interleukin-10 (IL-10) plays a key role in immunosuppressive and anti-angiogenic
      process, suggesting its possible involvement in carcinogenesis. A haplotype
      formed by polymorphisms at positions -1082 G/A (rs1800896), -819 T/C (rs1800871),
      and -592 A/C (rs1800872) from the transcriptional start site in the promoter
      region of the IL-10 gene is a strong determinant for IL-10 production. We
      systematically reviewed the evidence of association between IL-10 promoter
      haplotype and cancer risk. Up to November 2011, databases including PubMed, and
      CNKI (China National Knowledge Infrastructure) were searched to access the
      relevant genetic association studies. Summary odds ratios and corresponding 95%
      confidence intervals (CIs) for this haplotype and cancer risk were estimated by
      using fixed or random-effect models when appropriate. Finally, 12 case-control
      studies with 2,090 cases and 4,224 controls were available for this study. The
      summary OR for cancer risk associated with the GCC haplotype was 1.47 (95 % CIs =
      1.25-1.72) when compared with ATA haplotype by random effects model. Similarly,
      significantly increased risks were observed both in Caucasian and in Non
      Caucasian. Our results suggested that haplotype in IL-10 promoter was involved in
      the development of cancer.

PMID- 22644145
TI  - Applications of stable isotope dimethyl labeling in quantitative proteomics.
AB  - Mass spectrometry has proven to be an indispensable tool for protein
      identification, characterization, and quantification. Among the possible methods
      in quantitative proteomics, stable isotope labeling by using reductive
      dimethylation has emerged as a cost-effective, simple, but powerful method able
      to compete at any level with the present alternatives. In this review, we briefly
      introduce experimental and software methods for proteome analysis using dimethyl
      labeling and provide a comprehensive overview of reported applications in the
      analysis of (1) differential protein expression, (2) posttranslational
      modifications, and (3) protein interactions.

PMID- 22644147
TI  - European Analytical Column no. 40.

PMID- 22644146
TI  - Bioreactor monitoring with spectroscopy and chemometrics: a review.
AB  - Biotechnological processes are crucial to the development of any economy striving
      to ensure a relevant position in future markets. The cultivation of
      microorganisms in bioreactors is one of the most important unit operations of
      biotechnological processes, and real-time monitoring of bioreactors is essential
      for effective bioprocess control. In this review, published material on the
      potential application of different spectroscopic techniques for bioreactor
      monitoring is critically discussed, with particular emphasis on optical fiber
      technology, reported for in situ bioprocess monitoring. Application examples are
      presented by spectroscopy type, specifically focusing on ultraviolet-visible,
      near-infrared, mid-infrared, Raman, and fluorescence spectroscopy. The spectra
      acquisition devices available and the major advantages and disadvantages of each
      spectroscopy are discussed. The type of information contained in the spectra and
      the available chemometric methods for extracting that information are also
      addressed, including wavelength selection, spectra pre-processing, principal
      component analysis, and partial least-squares. Sample handling techniques (flow
      and sequential injection analysis) that include transport to spectroscopic
      sensors for ex-situ on-line monitoring are not covered in this review.

PMID- 22644148
TI  - Probing a myth: does the younger generation of scientists have it easier?

PMID- 22644150
TI  - Potential of MALDI-TOF mass spectrometry as a rapid detection technique in plant
      pathology: identification of plant-associated microorganisms.
AB  - Plant diseases caused by plant pathogens substantially reduce crop production
      every year, resulting in massive economic losses throughout the world. Accurate
      detection and identification of plant pathogens is fundamental to plant pathogen
      diagnostics and, thus, plant disease management. Diagnostics and disease
      management strategies require techniques to enable simultaneous detection and
      quantification of a wide range of pathogenic and non-pathogenic microorganisms.
      Over the past decade, rapid development of matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) techniques
      for characterization of microorganisms has enabled substantially improved
      detection and identification of microorganisms. In the biological sciences, MALDI
      TOF MS is used to analyze specific peptides or proteins directly desorbed from
      intact bacteria, fungal spores, nematodes, and other microorganisms. The ability
      to record biomarker ions, in a broad m/z range, which are unique to and
      representative of individual microorganisms, forms the basis of taxonomic
      identification of microorganisms by MALDI-TOF MS. Recent advances in mass
      spectrometry have initiated new research, i.e. analysis of more complex microbial
      communities. Such studies are just beginning but have great potential for
      elucidation not only of the interactions between microorganisms and their host
      plants but also those among different microbial taxa living in association with
      plants. There has been a recent effort by the mass spectrometry community to make
      data from large scale mass spectrometry experiments publicly available in the
      form of a centralized repository. Such a resource could enable the use of MALDI
      TOF MS as a universal technique for detection of plant pathogens and non
      pathogens. The effects of experimental conditions are sufficiently understood,
      reproducible spectra can be obtained from computational database search, and
      microorganisms can be rapidly characterized by genus, species, or strain.

PMID- 22644151
TI  - Implementation of comprehensive two-dimensional gas chromatography-time-of-flight
      mass spectrometry for the simultaneous determination of halogenated contaminants
      and polycyclic aromatic hydrocarbons in fish.
AB  - In the presented study, comprehensive two-dimensional gas chromatography coupled
      to time-of-flight mass spectrometry (GC * GC-TOFMS) was shown to be a powerful
      tool for the simultaneous determination of various groups of contaminants
      including 18 polychlorinated biphenyls (PCBs), seven polybrominated diphenyl
      ethers (PBDEs), and 16 polycyclic aromatic hydrocarbons (PAHs). Since different
      groups of analytes (traditionally analyzed separately) were included into one
      instrumental method, significant time savings were achieved. Following the
      development of an integrated sample preparation procedure for an effective and
      rapid isolation of several groups of contaminants from fish tissue, the GC * GC
      TOFMS instrumental method was optimized to obtain the best chromatographic
      resolution and low quantification limits (LOQs) of all target analytes in a
      complex mixture. Using large-volume programmable temperature vaporization, the
      following LOQs were achieved-PCBs, 0.01-0.25 MUg/kg; PBDEs, 0.025-5 MUg/kg; PAHs
      0.025-0.5 MUg/kg. Furthermore, several capillary column combinations (BPX5,
      BPX50, and Rxi-17Sil-ms in the first dimension and BPX5, BPX50, Rt-LC35, and HT8
      in the second dimension) were tested during the experiments, and the optimal
      separation of all target analytes even of critical groups of PAHs (group (a):
      benz[a]anthracene, cyclopenta[cd]pyrene and chrysene; group (b):
      benzo[b]fluoranthene, benzo[j]fluoranthene and benzo[k]fluoranthene; group (c):
      dibenz[ah]anthracene, indeno[1,2,3-cd]pyrene and benzo[ghi]perylene) was observed
      on BPX5 * BPX50 column setup. Moreover, since the determination of target
      analytes was performed using TOFMS detector, further identification of other non
      target compounds in real life samples was also feasible.

PMID- 22644149
TI  - Beyond nC60: strategies for identification of transformation products of
      fullerene oxidation in aquatic and biological samples.
AB  - Owing to their exceptional properties and versatility, fullerenes are in
      widespread use for numerous applications. Increased production and use of
      fullerenes will inevitably result in accelerated environmental release. However,
      study of the occurrence, fate, and transport of fullerenes in the environment is
      complicated because a variety of surface modifications can occur as a result of
      either intentional functionalization or natural processes. To gain a better
      understanding of the effect and risk of fullerenes on environmental health, it is
      necessary to acquire reliable data on the parent compounds and their congeners.
      Whereas currently established quantification methods generally focus on analysis
      of unmodified fullerenes, we discuss in this review the occurrence and analysis
      of oxidized fullerene congeners (i.e., their corresponding epoxides and
      polyhydroxylated derivatives) in the environment and in biological specimens. We
      present possible strategies for detection and quantification of parent
      nanomaterials and their various derivatives.

PMID- 22644152
TI  - Chiral HPLC analysis of donepezil, 5-O-desmethyl donepezil and 6-O-desmethyl
      donepezil in culture medium: application to fungal biotransformation studies.
AB  - An high performance liquid chromatography (HPLC) method for the enantioselective
      determination of donepezil (DPZ), 5-O-desmethyl donepezil (5-ODD), and 6-O
      desmethyl donepezil (6-ODD) in Czapek culture medium to be applied to
      biotransformation studies with fungi is described for the first time. The HPLC
      analysis was carried out using a Chiralpak AD-H column with
      hexane/ethanol/methanol (75:20:5, v/v/v) plus 0.3 % triethylamine as mobile phase
      and UV detection at 270 nm. Sample preparation was carried out by liquid-liquid
      extraction using ethyl acetate as extractor solvent. The method was linear over
      the concentration range of 100-10,000 ng mL(-1) for each enantiomer of DPZ (r >=
      0.9985) and of 100-5,000 ng mL(-1) for each enantiomer of 5-ODD (r >= 0.9977) and
      6-ODD (r >= 0.9951). Within-day and between-day precision and accuracy evaluated
      by relative standard deviations and relative errors, respectively, were lower
      than 15 % for all analytes. The validated method was used to assess DPZ
      biotransformation by the fungi Beauveria bassiana American Type Culture
      Collection (ATCC) 7159 and Cunninghamella elegans ATCC 10028B. Using the fungus
      B. bassiana ATCC 7159, a predominant formation of (R)-5-ODD was observed while
      for the fungus C. elegans ATCC 10028B, DPZ was biotransformed to (R)-6-ODD with
      an enantiomeric excess of 100 %.

PMID- 22644153
TI  - In-air broad beam ionoluminescence microscopy as a tool for rocks and stone
      artworks characterisation.
AB  - Broad beam ionoluminescence (IL) microscopy is a promising technique for the non
      destructive characterisation of rocks and stone objects. Luminescence imaging by
      means of broad ion beams has been sporadically used by other authors but, to our
      knowledge, its potential has not yet been fully investigated, neither in
      geological science nor in other fields. The in-air broad beam IL microscope was
      developed and installed at the INFN-LABEC external microbeam in Florence. Similar
      to the cathodoluminescence (CL) microscope, the apparatus exploits a CCD colour
      camera collecting images (few square millimetres wide, with ~10-MUm spatial
      resolution) of the luminescence emitted by the sample hit by a defocused
      megaelectron volt (MeV) proton beam. The main differences with the well
      established and widespread CL are the possibility of working in air (no sampling
      or conductive coatings required) and the possibility of combining the analysis
      with microbeam analysis, such as, for example, MU-IL and MU-PIXE (particle
      induced X-ray emission). To show the potential of the technique, IL images of
      thin sections of lapis lazuli are compared with those obtained by means of an in
      vacuum cold CL. An application to the study of stone artworks is also reported.
      This technique and apparatus will provide a valuable help for interdisciplinary
      applications, e.g. in geological sciences and in the cultural heritage field.

PMID- 22644154
TI  - Development of a biosensor for human blood: new routes to body fluid
      identification.
AB  - The identification of human blood at a crime scene can provide crucial
      information to an investigation whilst also providing a source of nuclear
      material which can be targeted for DNA profiling. Here, we report on the
      development of an immunofluorescent biosensor for the identification of human
      blood which has the potential to overcome the drawbacks of the current body fluid
      identification techniques. An antibody (Ab) raised against human erythrocytes was
      conjugated to fluorescent semiconductor quantum dots (QDs) by sulfhydryl
      chemistry. The conjugation was verified by agarose gel electrophoresis and
      immunohistochemistry. Incubation of liquid blood samples with the conjugated
      nanocrystals was shown to quench the fluorescence emission spectra in a
      concentration-dependent manner. A different effect was observed with unconjugated
      QDs incubated in blood. Full profiles were obtained from blood samples previously
      treated with the Ab-QDs, demonstrating that the method does not interfere with
      DNA profiling. To our knowledge, this is the first example of a hybrid Ab-QD
      sensor that has the potential to be employed for the identification of human
      blood. The results of this study are expected to open up a new research direction
      in the field of body fluid detection.

PMID- 22644155
TI  - Real-time analysis of aromatics in combustion engine exhaust by resonance
      enhanced multiphoton ionisation time-of-flight mass spectrometry (REMPI-TOF-MS):
      a robust tool for chassis dynamometer testing.
AB  - Resonance-enhanced multiphoton ionisation time-of-flight mass spectrometry (REMPI
      TOF-MS) is a robust method for real-time analysis of monocyclic and polycyclic
      aromatic hydrocarbons in complex emissions. A mobile system has been developed
      which enables direct analysis on site. In this paper, we utilize a multicomponent
      calibration scheme based on the analytes' photo-ionisation cross-sections
      relative to a calibrated species. This allows semi-quantification of a great
      number of components by only calibrating one compound of choice, here toluene.
      The cross-sections were determined by injecting nebulised solutions of aromatic
      compounds into the TOF-MS ion source with the help of a HPLC pump. Then, REMPI
      TOF-MS was implemented at various chassis dynamometers and test cells and the
      exhaust of the following vehicles and engines investigated: a compression
      ignition light-duty (LD) passenger car, a compression ignition LD van, two spark
      ignition LD passenger cars, 2 two-stroke mopeds, and a two-stroke engine of a
      string gas trimmer. The quantitative time profiles of benzene are shown. The
      results indicate that two-stroke engines are a significant source for toxic and
      cancerogenic compounds. Air pollution and health effects caused by gardening
      equipment might still be underestimated.

PMID- 22644156
TI  - Influence of secondary preparative parameters and aging effects on PLGA particle
      size distribution: a sedimentation field flow fractionation investigation.
AB  - Poly(lactic-co-glycolic acid) particles in the 200-400-nm size range were
      formulated through nanoprecipitation and solvent evaporation methods. Different
      concentrations of the polymer and stabilizer (Pluronic(r) F 68) were tested in
      order to identify the best conditions for making poly(lactic-co-glycolic acid)
      particles of suitable size, stable in time, and to be used as carriers for brain
      targeting drugs. The particles with the best characteristics for delivery system
      design were those formulated by nanoprecipitation with an organic/water phase
      ratio of 2:30, a polymer concentration of 25 mg/mL, and a surfactant
      concentration of 0.83 mg/mL; their surface charge was reasonably negative
      (approximately -27 mV) and the average size of the almost monodisperse population
      was roughly 250 nm. Particle characterization was obtained through zeta-potential
      measurements, scanning electron microscope observations, and particle size
      distribution determinations; the latter achieved by both photon-correlation
      spectroscopy and sedimentation field flow fractionation. Sedimentation field flow
      fractionation, which is considered more reliable than photon-correlation
      spectroscopy in describing the possible particle size distribution modifications,
      was used to investigate the effects of 3 months of storage at 4  degrees C had on
      the lyophilized particles. Figure Particle size ditribution from the SdFFF and
      the PCS techniques.

PMID- 22644157
TI  - Sellar meningiomas: an endocrinologic perspective.
AB  - To review the clinical manifestations and outcomes of those with sellar
      meningiomas treated surgically at Mayo Clinic between 1975 and 2003. This is a
      retrospective chart and pathology review of 17 patients with a diagnosis of
      purely or largely intrasellar meningiomas treated surgically at our institution.
      Data in regards to presentation, endocrine hormonal status, surgical approach,
      pathology findings, outcome and adjunctive treatment were abstracted from the
      medical records. The majority of patients present with visual disturbances. All
      17 tumors were WHO grade I. Surgical cure was achieved in 53 % after initial
      surgery. Postsurgical hypopituitarism occurred with high frequency. A substantial
      proportion of patients required subsequent surgical intervention or adjunctive
      treatment with external beam radiation. Sellar meningiomas are technically
      challenging and carry a high risk for visual disturbance and pituitary hormonal
      abnormalities. Many patients experience persistent disease requiring further
      intervention. These patients require long-term follow-up for evaluation of
      recurrence or development of new pituitary hormonal insufficiencies.

PMID- 22644158
TI  - Synthetic control of framework zinc purinate crystallisation and properties of a
      large pore, decorated, mixed-linker RHO-type ZIF.
AB  - A novel form of mixed-linker ZIF with the RHO topology is one of four zinc
      imidazolate frameworks prepared with purine and 2-nitroimidazole. In this
      structure the linkers order to give a large pore solid with a high pore volume
      and an unusual symmetry and linker orientation. It possesses extra-framework zinc
      imidazolate units decorating the internal surface which can be removed to give
      high porosity.

PMID- 22644159
TI  - Pain stress and headache.
AB  - The association between pain and stress is an old one, but still it is not really
      clear who comes first. Pain induces stress, and stress induces pain. Pain is part
      of our homeostatic system and in this way is an emotion, i.e., it tells us that
      something is out-of-order (control), and emotion drives our behavior and one
      behavior is stress response. Stress comes from ourselves: the imagination we have
      or would like to have of us, from the image others give of us, from the goals we
      assume it is necessary to reach for our well-being or the goals others want us to
      fulfill. Stress comes from our social condition and the condition we would like,
      stress comes from dangerous situations we cannot control. Headache easily fits in
      the picture.

PMID- 22644160
TI  - Laboratory tools for assessing neuropathic pain.
AB  - Neuropathic pain, i.e. pain arising as a direct consequence of a lesion or
      disease of the somatosensory system, affects about the 7 % of the general
      population. In this short review, we describe the most reliable laboratory tools
      for assessing neuropathic pain, such as quantitative sensory testing, laser
      evoked potential recordings and skin biopsy, procedures that selectively assess
      nociceptive pathways.

PMID- 22644161
TI  - Allodynia and migraine.
AB  - An impaired processing of sensory afferents in the brainstem plays a key role in
      the development of migraine attack and for many of its clinical aspects. The
      repetition or prolonged of painful stimuli over time would be able to produce a
      prolonged and reversible increase of excitability and synaptic efficacy in the
      nociceptive pathways of the central nervous system. This phenomenon, known as
      sensitization, involves specifically the caudal trigeminal nucleus. Being an
      aspect of untreated migraine, allodynia is more common in patients with chronic
      migraine and migraine with aura, often associated with motor and sensory symptoms
      sometimes present during the attacks. The presence of allodynia in the course of
      migraine attack greatly increases the disability of the patient and its
      recognition, as well as from a therapeutic point of view, it is essential in the
      management of migraine patients.

PMID- 22644162
TI  - New prospects in the taxonomic classification of primary headaches.
AB  - In the field of primary headaches, we have a very useful classification tool for
      the clinical characterization of individual attacks, but we lack a classification
      tool for the characterization of primary headache patients. Just because the
      reasons for this lack have been partially overcome by the knowledge that has been
      gained in the meantime and because clinicians and researchers are increasingly
      pressed to find new and reliable ways to manage certain primary headache forms,
      including so-called chronic migraine, we now have an imperative commitment to
      provide a syndrome classification.

PMID- 22644163
TI  - A redefinition of primary headache: chronic migraine.
AB  - In the field of so-called chronic daily headache, it is not easy for migraine
      that worsens progressively until it becomes daily or almost daily to find a
      precise and universally recognized place within the current international
      headache classification systems. A proposal is advanced to differentiate between
      a form of high-frequency migraine without aura (10-20 days of headache per month
      for at least 3 months), to be considered as a migraine without aura subtype, and
      a form of transformed migraine (TM), to be considered as a complication of
      migraine. TM--a name that should be preferred to chronic migraine (CM)--would
      then replace the latter, from which it would distinguish itself by the more
      restrictive diagnostic criteria (at least 20 days of headache per month for at
      least 1 year, with no more than 5 consecutive days free of symptoms; same
      clinical features of migraine without aura for at least 10 of those 20 days).

PMID- 22644165
TI  - Medication overuse headache (MOH): complication of migraine or secondary
      headache?
AB  - In the field of chronic forms of headache, medication overuse headache (MOH)
      seems to be a problematic argument as the correct position of this clinical
      condition in the International Headache Society (IHS) classification is not clear
      yet. In 1988, when IHS organized the first classification of the different forms
      of headache, the clinical problem of medication overuse was included in the
      section eight of the IHS; during the last decades the criteria of the
      classification changed, and now this form is included in the classification
      system as a clinical condition distinguished from chronic migraine and other
      chronic forms of headache. The different models of classification are discussed
      and the clinical and practical aspects are considered in this paper.

PMID- 22644164
TI  - Sinus venous stenosis, intracranial hypertension and progression of primary
      headaches.
AB  - The recently advanced hypothesis that idiopathic intracranial hypertension
      without papilledema (IIHWOP) is a powerful risk factor for the progression of
      pain in individuals prone to episodic primary headache implies that IIHWOP is
      much more prevalent than it is believed to be in the general population and that
      it can run almost asymptomatic in most of the affected individuals. In this
      review, we discuss the evidence available supporting that: (a) sinus venous
      stenosis-associated IIHWOP is much more prevalent than believed in the general
      population and can run without symptoms or signs of raised intracranial pressure
      in most of individuals affected, (b) sinus venous stenosis is a very sensitive
      and specific predictor of intermittent or continuous idiopathic intracranial
      hypertension with or without papilledema, even in asymptomatic individuals, (c)
      in primary headache prone individuals, a comorbidity with a hidden stenosis
      associated IIHWOP represents a very common, although largely underestimated,
      modifiable risk factor for the progression and refractoriness of headache.

PMID- 22644166
TI  - Peripheral neuromodulation in chronic migraine.
AB  - Patients with chronic migraines are often refractory to medical treatment.
      Therefore, they might need other strategies to modulate their pain, according to
      their level of disability. Neuromodulation can be achieved with several tools:
      meditation, biofeedback, physical therapy, drugs and electric neurostimulation
      (ENS). ENS can be applied to the central nervous system (brain and spinal cord),
      either invasively (cortical or deep brain) or non-invasively [cranial
      electrotherapy stimulation, transcranial direct current stimulation and
      transcranial magnetic stimulation]. Among chronic primary headaches, cluster
      headaches are most often treated either through deep brain stimulation or
      occipital nerve stimulation because there is a high level of disability related
      to this condition. ENS, employed through several modalities such as
      transcutaneous electrical nerve stimulation, interferential currents and pulsed
      radiofrequency, has been applied to the peripheral nervous system at several
      sites. We briefly review the indications for the use of peripheral ENS at the
      site of the occipital nerves for the treatment of chronic migraine.

PMID- 22644167
TI  - Drug-resistant chronic migraine: the Italian GON project.
AB  - Chronic daily headache is a major problem due to severe disability and high socio
      economic costs. In the last years, some trials have shown potential benefit from
      new therapeutic approach by occipital neurostimulation techniques, already
      applied with some success for the treatment of chronic cluster headache. Due to
      the extremely heterogeneous population suffering from refractory chronic daily
      headaches, we propose a national multicenter experimental study involving Italian
      ANIRCEF Headache Centres with the aim to evaluate the efficacy of occipital
      neurostimulation in a selected group representative for the drug-resistant
      chronic migraine. Patients with chronic migraine according to Manzoni's modified
      IHS criteria-2011, with or without medication overuse headache, will be selected.
      Duration of illness should be at least 2 years and pharmacological refractoriness
      defined strictly for experimental-surgical purposes as those patients who have
      properly tried without success almost all available classes of prophylactic
      medications. Those presenting with medication overuse should have tried at least
      two previous detoxification treatments. A full psychopathological assessment will
      be performed by a psychiatrist, to exclude mainly psychotic disorder, ongoing
      severe status of an affective disorder, severe post traumatic stress disorder.
      Headache characteristics and abortive treatments used will be reported daily on a
      predisposed diary during 3-month baseline and continuously through the post
      implant follow up, while disability and QoL scale (MIDAS, SF-12) will be
      completed baseline, 6 and 12 months after implant.

PMID- 22644168
TI  - Migraine: risk factor and comorbidity.
AB  - The burden of migraine strongly increases considering its linkage with other
      psychiatric, neurological, cardiovascular and cerebrovascular diseases. Migraine
      is positively associated with many disorders: some are confirmed by several
      studies whereas others remain uncertain or controversial. The association with
      some disorders is not simply due to concomitance but it implies a linkage in
      terms of causality. Highlighting these relationships is important to improve
      treatment strategies, broaden our knowledge of the pathophysiology and understand
      if migraine is per se a modifiable risk factor for some disorders.

PMID- 22644169
TI  - Migraine and sleep disorders.
AB  - The burden of migraine strongly increases, considering its linkage with sleep
      disorders. Migraine is positively associated with many sleep-complaint disorders;
      some are confirmed by several studies, such as restless leg syndrome, whereas
      others still remain uncertain or controversial, e.g. narcolepsy. Many studies
      have investigated the association between headache and other sleep disturbances
      such as daytime sleepiness, insomnia, snoring and/or apnea, but only a few have
      focused on migraine. Highlighting the comorbidity between migraine and sleep
      disorders is important to improve treatment strategies and to extend the
      knowledge of migraine pathophysiology.

PMID- 22644170
TI  - Migraine and cardiovascular diseases.
AB  - Migraine has complex relationships with cerebrovascular and cardiovascular
      disorders but also with cardiac anomalies. Patients affected by migraine with
      aura have an increased prevalence of right-to-left shunt due to patent foramen
      ovale or pulmonary arteriovenous malformations. The association between ischemic
      heart disease, cardiovascular mortality and migraine remains unsettled. The
      debate focuses on a physiopathological link between migraine and cardiovascular
      diseases or a higher prevalence of risk factors in migraineurs.

PMID- 22644171
TI  - Migraine and small vessel diseases.
AB  - It is remarkable that migraine is a prominent part of the phenotype of several
      genetic vasculopathies affecting small cerebral vessels, including cerebral
      autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy, retinal vasculopathy with cerebral leukodystrophy and
      hereditary infantile hemiparesis, retinal arteriolar tortuosity and
      leucoencephalopathy. Moreover, several studies have reported an association
      between migraine and white matter lesions or clinically silent infarct-like
      abnormalities in the posterior circulation. In this review, we focus on genetic
      vasculopathies associated with migraine and speculate about the
      pathophysiological mechanism that can explain this comorbidity.

PMID- 22644172
TI  - Migraine and movement disorders.
AB  - A large series of clinical and experimental observations on the interactions
      between migraine and the extrapyramidal system are available. Some previous
      studies reported high frequency of migraine in some basal ganglia (BG) disorders,
      such as essential tremor (ET), Tourette's syndrome (TS), Sydenham's chorea and
      more recently restless legs syndrome (RLS). For example, the frequency of
      migraine headache in a clinic sample of TS patients was found nearly fourfold
      more than that reported in the general population. To the best of our knowledge,
      no controlled studies have been conducted to determine a real association. ET and
      migraine headache have been considered comorbid diseases on the basis of
      uncontrolled studies for many years. In a recent Italian study, this comorbid
      association has been excluded, reporting no significant differences in the
      frequency of lifetime and current migraine between patients with ET and controls.
      Among mostly common movement disorders, RLS has been recently considered as
      possibly comorbid with migraine. Studies in selected patient groups strongly
      suggest that RLS is more common in migraine patients than in control populations,
      although no population-based study of the coincidence of migraine and RLS has yet
      been identified. The exact mechanisms and contributing factors for a positive
      association between migraine and RLS remain unclear. A number of possible
      explanations have been offered for the association of RLS and primary headache,
      but the three most attractive ones are a hypothetical dopaminergic dysfunction
      and dysfunctional brain iron metabolism, a possible genetic linkage and a sleep
      disturbance. More recently, the role of BG in pain processing has been confirmed
      by functional imaging data in the caudate, putamen and pallidum in migraine
      patients. A critical appraisal of all these clinical and experimental data
      suggests that the extrapyramidal system is somehow related to migraine. Although
      the primary involvement of extrapyramidal system in the pathophysiology of
      migraine cannot as yet be proven, a more general role in the processing of
      nociceptive information and/or maybe part of the complex behavioral adaptive
      response that characterizes migraine may be suggested.

PMID- 22644173
TI  - Frovatriptan versus zolmitriptan for the acute treatment of migraine with aura: a
      subgroup analysis of a double-blind, randomized, multicenter, Italian study.
AB  - Migraine with aura affects ~20-30 % of migraineurs and it is much less common
      than migraine without aura. The aim of this study was to compare the efficacy of
      frovatriptan 2.5 mg and zolmitriptan 2.5 mg in the treatment of migraine with
      aura. Analysis was carried out in a subset of 18 subjects with migraine with aura
      (HIS criteria) out of the 107 enrolled in a multicenter, randomized, double
      blind, cross-over study. According to the study design, each patient had to treat
      three episodes of migraine in no more than 3 months with one drug, before
      switching to the other treatment. The rate of pain-free episodes at 2 h was
      significantly (p < 0.05) larger under frovatriptan (45.8 %) than under
      zolmitriptan (16.7 %). Pain free at 4 h, pain relief at 2 and 4 h and recurrent
      episodes were similar between the two treatments, while sustained pain-free
      episode was significantly (p < 0.05) more frequent during frovatriptan treatment
      (33.3 vs. 8.3 % zolmitriptan). Our study suggests that frovatriptan is superior
      to zolmitriptan in the immediate treatment of patients with migraine with aura,
      and it is capable of maintaining its acute analgesic effect over 48 h.

PMID- 22644174
TI  - Efficacy of frovatriptan versus other triptans in the acute treatment of
      menstrual migraine: pooled analysis of three double-blind, randomized, crossover,
      multicenter studies.
AB  - The objective of this study was to review the efficacy and safety of frovatriptan
      (F) versus rizatriptan (R), zolmitriptan (Z) and almotriptan (A), in women with
      menstrually related migraine (IHS criteria) through a pooled analysis of three
      individual studies. Subjects with a history of migraine with or without aura were
      randomized to F 2.5 mg or R 10 mg (study 1), F or Z 2.5 mg (study 2), and F or A
      12.5 mg (study 3). The studies had an identical multicenter, randomized, double
      blind, crossover design. After treating three episodes of migraine in no more
      than 3 months with the first treatment, patients had to switch to the next
      treatment for other 3 months. 346 subjects formed intention-to-treat population
      of the main study; 280 of them were of a female gender, 256 had regular menses
      and 187 were included in the menstrual migraine subgroup analysis. Rate of pain
      free at 2, 4 and 24 h was 23, 52 and 67 % with F and 30, 61 and 66 % with
      comparators (P = NS). Pain relief episodes at 2, 4 and 24 h were 37, 60 and 66 %
      for F and 43, 55 and 61 % for comparators (P = NS). Rate of recurrence was
      significantly (P < 0.05) lower under F either at 24 h (11 vs. 24 % comparators)
      or at 48 h (15 vs. 26 % comparators). Number of menstrual migraine attacks
      associated with drug-related adverse events was equally low (P = NS) between F (5
      %) and comparators (4 %).

PMID- 22644175
TI  - Is migraine a risk factor for the occurrence of eating disorders? Prevalence and
      biochemical evidences.
AB  - The eating disorders (ED), anorexia nervosa (AN) and bulimia nervosa (BN), are
      severe psychiatric and somatic conditions occurring mainly in young woman.
      Although the aetiology is largely unknown, same evidences suggest that biological
      and psychological factors play a relevant role in the pathogenesis, along with
      monoamine, indole and same hypothalamic hormonal dysfunctions. Migraine is
      characterized by similar metabolic and psychological anomalies suggesting that a
      possible relationship exists between the two pathological conditions. To
      understand the possible relationship between migraine and ED, we have
      investigated the prevalence of migraine and the other primary headaches in a
      large group of AN and BN patients. In addition, we have studied the role of
      tyrosine metabolism in the same group of AN and BN young woman sufferers. In
      particular, we measured plasma levels of elusive amines: tyramine (Tyr) and
      octopamine (Oct) and catecholamines: noradrenalin (NE), dopamine (DA). The
      results of this study show that the prevalence of migraine in the woman affected
      by ED is very high (<75 %). The levels of Tyr and DA were higher and levels of NE
      were lower in the ED patients in respect to the control subjects. These
      biochemical findings suggest that abnormalities of limbic and hypothalamic
      circuitries play a role in the pathogenesis of ED. The very high prevalence of
      migraine in our group of ED sufferers and the biochemical profile of migraine,
      similar to that of ED patients shown in this study, suggest that migraine may
      constitute a risk factor for the occurrence of ED in young females. This
      hypothesis is supported by the onset of migraine attacks that initiated, in the
      majority of the patients, before the occurrence of ED symptoms.

PMID- 22644176
TI  - Food as trigger and aggravating factor of migraine.
AB  - A relevant proportion of patients say that their migraine attacks may be
      precipitated by dietary items, the percentage of patients reporting foods as
      trigger ranging in different study from 12 to 60 %. Fasting, alcohol, chocolate
      and cheese are the dietary precipitating factors more frequently reported. The
      finding that diet-sensitive migraineurs are usually sensitive to several and
      different foods, lead to the hypothesis of antigenic similarities between these
      disparate foods or common chemical constituents, but a clear scientific
      explanation of the mechanisms implicated in the development of migraine attacks
      supposedly precipitated by food is still lacking. The possibility that the
      elimination diets based on the hypothesis of food hypersensivity IgE or IgG
      mediated improve migraine has been explored in different studies but the results
      are inconclusive. Fasting as trigger for migraine is frequently reported. Some
      migraineurs show reactive hypoglycaemia due to diet-induced hyperinsulinism. In
      conclusion, identification of environmental factors (including dietary factors)
      that consistently trigger migraine in some subjects may be helpful to reduce
      attacks frequency. The biological mechanism by means of triggers in general and
      food in particular precipitate migraine attacks remains obscure.

PMID- 22644177
TI  - Migraine and metabolism.
AB  - Migraine is a chronic disorder with complex pathophysiology involving both
      neuronal and vascular mechanisms. Migraine is associated with an increased risk
      of vascular disorders, such as stroke and coronary heart disease. Obesity and
      diabetes are metabolic disorders with a complex association with migraine.
      Insulin resistance, which represents the main causal factor of diseases involved
      in metabolic syndrome, is more common in patients with migraine. A better
      understanding of the relationship between metabolic syndrome and migraine may be
      of great clinical interest for migraine management.

PMID- 22644178
TI  - Headache, eating and sleeping behaviors and lifestyle factors in preadolescents
      and adolescents: preliminary results from an Italian population study.
AB  - Several dietary and lifestyle habits can be associated with headaches or with
      their progression to chronic forms in adults. We report the results of the first
      population study performed in Italy on a sample of preadolescent and adolescent
      students to assess the possible association between headache and specific habits
      and lifestyle factors. Preliminary data from 800 questionnaires showed that 365
      subjects had headaches, which were of moderate-severe intensity, associated with
      anorexia, and caused absence from school in more than 50 % of students. The main
      finding was the evidence of a clear association between headache and irregular
      intake of meals (especially irregular breakfast) and sleep disturbance with
      significant differences when subjects with and without headache were compared. If
      confirmed, these results are likely to influence clinical practice as well to
      address educational programs in preadolescents and adolescents.

PMID- 22644180
TI  - From neuroimaging to clinical setting: what have we learned from migraine pain?
AB  - In the last 15 years, the neuroimaging of patients suffering from migraine with
      or without aura has improved our understanding of the mechanisms underlying the
      pathophysiology of the disease. A great number of studies based on modern imaging
      techniques, such as structural imaging and functional imaging emphasize that in
      migraine patients suffering from repetitive pain attacks, both significant
      abnormalities of function and diffuse structural changes of brain white and gray
      matter become striking features of the disease. The hypothesis that migraine pain
      is due to a global brain disorder with substantial brainstem involvement leading
      to secondary blood flow changes in the posterior circulation is reinforced by
      several elegant studies. Clinical application of functional imaging findings in
      migraine is yet to be considered, since the specificity of some results has to be
      determined. Nevertheless, functional MRI techniques have a vast potential for
      exploring the pathophysiology of pain in migraine patients.

PMID- 22644179
TI  - Functional neuroimaging in migraine: usefulness for the clinical neurologist.
AB  - Migraine is a common, multifactorial disorder, typically characterized by
      recurrent attacks of throbbing unilateral headache, autonomic nervous system
      dysfunction and, in approximately one-third of cases, neurological transient
      symptoms (migraineous aura). The diagnosis of primary headaches is exclusively a
      clinical task but, for this reason, it is sometimes subjective and arbitrary.
      However, until today no single diagnostic tool is able to define, ensure or
      differentiate idiopathic headache syndromes, although, in the clinical setting,
      conventional neuroimaging techniques are often widely and improperly used in
      headache patients. Recent years have seen rapid growth of neuroimaging
      methodology which has provided new insights into functional brain organization of
      migraine patients. Although functional magnetic resonance imaging has today
      little or no value in clinical practice, clinicians role is crucial since without
      a proper clinical selection neuroimaging studies could generate inconclusive
      results. Likewise, functional neuroimaging is crucial for clinicians in order to
      further elucidate pathophysiological mechanisms underlying this complex and often
      disabling disease and to provide new therapeutical approaches for migraine
      patients.

PMID- 22644181
TI  - From neuroimaging to patients' bench: what we have learnt from trigemino
      autonomic pain syndromes.
AB  - Trigeminal autonomic cephalalgias (TACs) are primary headaches including cluster
      headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform
      headache attacks with conjunctival injection and tearing (SUNCT). A number of
      neuroimaging studies have been conducted in last decade showing involvement of
      brain areas included in the pain matrix. Apart from pain matrix involvement,
      other neuroimaging findings data deserve special attention. The hypothalamic
      activation reported in the course of TAC attacks coupled with the efficacy of
      hypothalamic neurostimulation to treat drug-resistant TAC forms clearly indicate
      the posterior hypothalamus as a crucial area in TAC pathophysiology. In animal
      models this brain area has been shown to modulate craniofacial pain; moreover,
      hypothalamic activation occurs in other pain conditions, suggesting that
      posterior hypothalamus has a more complex role in TAC pathophysiology rather than
      simply being considered as a trigger. In contrast, hypothalamic activation may
      serve as a crucial area in terminating rather than triggering attacks. It also
      could lead to a central condition facilitating initiation of TAC attacks.

PMID- 22644182
TI  - The pain in migraine beyond the pain of migraine.
AB  - Migraine is a complex and often disabling brain disorder that affects about 15 %
      of the population. The diagnosis of migraine is based on clinical features as
      proposed by the International Headache Society criteria but they are somewhat
      subjective and arbitrary. Functional neuroimaging of patients with migraine has
      been recently employed to study the underlying pathophysiology of headache. These
      studies have suggested that migraine involves functional and structural
      plasticity of both central and peripheral nervous system. Insights into the
      fundamental physiology of migraine have been limited by the lack of methods
      available to detect the pathophysiological background of critical moment of
      migraine attack onset that is greatly different from the onset of pain or pain
      phase of a migraine attack. In order to overcome methodological caveats in
      detecting "migraine origin" or a "migraine generator", functional brain imaging
      has been lately dominated by experimental acute-pain research. Along this
      research line functional imaging using experimental pain stimulation have greatly
      improved our knowledge about physiological or dysfunctional neuronal activity
      pattern in patients with migraine, but at the same time, it is important to
      emphasize that experimental pain is different from spontaneous migraine pain.

PMID- 22644183
TI  - Migraine and depression: bidirectional co-morbidities?
AB  - Even if the bidirectional co-morbidity between migraine and depression has been
      supported by epidemiological and genetic studies, many aspects of this
      association have not been completely understood. This may be due to the
      heterogeneous character of migraine and depression as well as to their
      multifactorial pathogenesis. In this review, we have briefly reported the more
      recent findings published about the co-morbidity between migraine and depression
      by discussing the above reported issues and the relative clinical and therapeutic
      implications.

PMID- 22644184
TI  - Premenstrual syndrome and migraine.
AB  - Premenstrual syndrome (PMS) includes a wide variety of physical, psychological,
      and cognitive symptoms that occur recurrently and cyclically during the luteal
      phase of the menstrual cycle and disappear soon after the onset of menstruation.
      Headache, often of migrainous type, is one of physical symptoms often reported in
      the diagnostic criteria for PMS. Menstrual migraine (MM) is a particular subtype
      of migraine occurring within the 2 days before and the 3 days after the onset of
      menses. According to this definition, therefore, some attacks of MM certainly
      occur in conjunction with the period of maximum exacerbation of PMS symptoms. The
      relationship between MM and PMS has been investigated through diary-based studies
      which have confirmed the possible correlation between these two conditions. In
      this paper we provide indications for the treatment of MM, making particular
      reference to those therapies that may be useful in the treatment of PMS symptoms.
      Even if triptans are the gold standard for the acute treatment, if symptomatic
      treatment is not sufficient one can resort to a short-term perimenstrual
      prophylaxis. Non-steroidal anti-inflammatory drugs have been demonstrated
      effective in MM prophylaxis. Among natural products there is some evidence of
      efficacy for magnesium, phytoestrogens, and ginkgolide B. Finally, also a
      combined oral contraceptive containing drospirenone, taken continuously for 168
      days, has shown promising results.

PMID- 22644185
TI  - Migraine and depression comorbidity: antidepressant options.
AB  - Migraine and mood depression demonstrate a high clinical relation and share, also
      with pain, neurobiological mechanisms, particularly neuro-transmettitorial and
      phlogistic ones. The choice of an antidepressant to treat both depression and
      migraine is determined by its efficacy, safety, and tolerability. Antidepressants
      share comparable effectiveness for the treatment of depressive disorders, but
      their efficacy on headache varies widely: Tricyclic antidepressants are more
      effective than SNRIs and SSRIs, but demonstrate dose-limiting side effects.

PMID- 22644186
TI  - The therapeutic future in headache.
AB  - There are many categories and individual types of headache and most have a
      variety of treatment protocols, while a few are best treated by just one
      medication. This paper will concentrate on acute care medications for migraine
      and discuss some new and future acute care treatments. There is not much to
      discuss about prevention, except that onabotulinumtoxinA has been approved for
      prevention of chronic migraine. Cluster headache will also be discussed, as there
      are some future treatments for acute care and prevention being studied at
      present. For the acute care of migraine in the US, we have seven triptans by
      tablet plus other routes and one non steroidal anti-inflammatory medication
      approved by the FDA that is currently available (Cambia brand of buffered
      diclofenac potassium for oral solution). There are several other acute care
      medications in various stages of development and there are three new methods of
      administering a triptan and others under investigation. The optimal acute care
      therapy for migraine should be faster, easier to use and more efficient with
      fewer adverse events than what is currently available. What follows is a brief
      review of the status in development for five of the many new acute care
      medications being investigated: the CGRP antagonist tablet telcagepant, the
      sumatriptan iontophoretic patch Zelrix, sumatriptan powder for use in the
      OptiNose apparatus, dihydroergotamine for oral inhalation (Levadex), civamide
      nasal solution for prevention of episodic cluster headache (Civanex) and
      sphenopalatine ganglion stimulation for acute cluster attacks in chronic cluster
      headaches. Other future treatments that will not be discussed include
      transcranial magnetic stimulation, a 5-HT(1F) agonist named alniditan, large
      conductance calcium-activated potassium channel openers, glial modulators or
      other medications and devices in early stages of development.

PMID- 22644187
TI  - Behavioral treatment of headaches: extending the reach.
AB  - Behavioral treatments (predominantly biofeedback, relaxation, and cognitive
      behavioral) have been utilized in headache management for many decades. Although
      effective, they have not been as widely implemented as desired, chiefly due to
      their time-intensive nature, special therapist qualifications, and patient costs.
      This paper focuses on ways to make these treatments more affordable and more
      readily accessible to patients. Various alternative delivery models have been
      explored. This paper reviews progress to date on three such approaches for
      treating recurrent headaches in adults--prudent limited office contact, Internet
      delivery, and mass media approaches. Clinical outcomes, advantages, and
      disadvantages of these approaches are reviewed in brief.

PMID- 22644188
TI  - Surgical treatment of primary headaches.
AB  - Neuromodulation for the treatment of drug-refractory cranial neuralgias
      constitutes an exciting field of research for physicians; in the last decade,
      several methodologies have been described which could help many patients to exit
      such desperate conditions; although the exact mechanisms of action of these
      techniques are still matter of debate, several experimental and neuroradiological
      modalities can help us to get near the concept of understanding them. In this
      paper, the authors summarize the most recent surgical procedures used to treat
      severe and pharmaco-resistant cranial painful conditions, along with brief
      descriptions of the results obtained in the several published so far.

PMID- 22644189
TI  - Future trends in drugs for migraine prophylaxis.
AB  - Migraine prevention hinges on a variety of non-specific drugs that mainly reduce
      neuronal hyperexcitability, the putative pathophysiological hallmark for
      migraine. The improved knowledge about migraine circuitry and neurobiology has
      prompted research to develop new specific migraine preventive medications
      targeted to innovative sites and mechanisms. Drugs designed to inhibit cortical
      spreading depression, for example tonabersat, might offer a useful option for the
      management of migraine with aura but not for migraine without aura. Inducible
      nitric-oxide synthase (iNOS) inhibition seems ineffective as a prophylactic
      strategy. Results are awaited from recent and ongoing phase II trials with
      glutamate receptor antagonists, third-generation antiepileptics, melatonin
      agonists, vitamin D3 and statins.

PMID- 22644190
TI  - Controversies in migraine: monotherapy.
AB  - Migraine patients with frequent and severe headaches need prophylaxis. The most
      used approach is monotherapy, i.e. one of the available preventive compounds is
      prescribed to the patient, testing its efficacy and tolerability during a
      treatment period of some months. Some clinicians use to add a second (or even a
      third) preventive compound to improve the effects of pharmacological prophylaxis,
      using an approach that can be defined as polytherapy. In this paper, the main
      advantages of monotherapy are briefly reviewed, taking into account several
      aspects: published evidence on polytherapy; the possibility to evaluate the
      adverse events of the prescribed treatment and to assess its real efficacy; the
      possibility of addressing different patient's needs, particularly the treatment
      of comorbidities and the development of an effective patient-physician
      communication.

PMID- 22644191
TI  - Polytherapy for migraine prophylaxis.
AB  - Migraine is a chronic neurological disorder with episodic manifestations,
      progressive in some individuals. Preventive treatment is recommended for patients
      with frequent or disabling attacks. A sizeable proportion of migraineurs in need
      of preventive treatment does not significantly benefit from monotherapy. This
      short review evaluates the role of pharmacological polytherapy in migraine
      prevention.

PMID- 22644192
TI  - Decision-making deficit in chronic migraine patients with medication overuse.
AB  - Patients with chronic migraine developing medication-overuse headache (MOH) show
      dependency-like behaviors such as loss of control over analgesics despite adverse
      consequences on headaches, high rates of relapse after withdrawal from
      symptomatic medications, and compromised social functioning. Neuroimaging
      research suggests a common pathophysiology between substance-use disorders and
      MOH, which involves functional alterations in fronto-striatal networks,
      particularly in the orbitofrontal region of prefrontal cortex. These findings
      could explain the impaired decision-making observed in substance-use disorders.
      We hypothesize that MOH could share fronto-striatal circuit dysfunction and
      relative decision-making deficit with addiction. We further examine whether this
      deficit is a persistent cognitive trait or a reversible consequence of medication
      overuse. This study shows a dataset of 50 patients with MOH before the
      detoxification. All patients underwent a complete neurological and psychiatric
      examination. Psychiatric examination consisted of a clinical interview,
      Structured Clinical Interview for DSM-IV TR Axis II Personality Disorders,
      Anxiety and Depression Hamilton Scales, Severity of Dependence Scale. The
      neurological examination included the migraine disability assessment
      questionnaire. Neuropsychological assessment of fronto-striatal circuits was
      investigated using the Iowa gambling task (IGT). Twenty patients monitored for
      any relapse into medication overuse had 12 months of follow-up. Our sample,
      characterized by high rates of disability and dependency-like behaviors,
      exhibited a deficit in IGT performance, indicating an overall impairment in
      decision-making. All the 20 patients showed neurological and psychiatric
      improvement at 12-month follow-up, notwithstanding the overuse relapse, but a
      persistent IGT deficit was found. To our knowledge this is the first study that
      assesses this cognitive function in patients with MOH. Medication-overuse
      headache seems to share a persistent decision-making deficit with substance abuse
      that confirms the orbitofrontal cortex hypometabolism described in literature
      from a neuropsychological perspective. Looking at these shared neurocognitive
      features, our results suggest that MOH could belong to the addiction spectrum.
      Fronto-striatal dysfunction could be a premorbid psychobiological condition of
      vulnerability explaining the clinical onset of medication overuse and recurrent
      relapses. We propose that IGT could be used to identify chronic migraine patients
      with higher risk for medication overuse and relapse.

PMID- 22644193
TI  - Late-onset cluster headache: some considerations about 73 cases.
AB  - Data in the literature on cluster headache (CH) indicate a mean age at onset of
      about 29-30 years; recently, however, cases have been reported with onset in old
      age. A review of age at onset in all CH patients (n = 693) followed at the
      University of Parma Headache Centre between 1976 and 2011 shows that 73 (10.5 %)
      patients began to suffer from CH after age 50. In these 73 patient, the gender
      (M:F) ratio was 1.4:1, while in the 620 patients with CH onset before age 50, it
      was 2.5:1. In the patients with CH onset after and before age 50, respectively,
      the distribution by CH subtype shows that the episodic-to-chronic ratio was 7.6:1
      and 7.9:1 in men and 1.5:1 and 7.8:1 in women. In episodic CH men with onset
      after 50 the average duration of active periods was 60 versus 39 days for those
      with onset before 50. In women, the duration was 80 and 42 days, respectively. In
      conclusion, our case review suggests that CH onset after age 50 is not rare,
      especially in women. Additionally, late onset represents a negative prognostic
      factor because, particularly in women, CH will more likely be a chronic form and
      even in episodic forms active periods will last longer.

PMID- 22644194
TI  - The real usefulness and indication for migraine diagnosis of neurophysiologic
      evaluation.
AB  - According to IHS criteria, a correct clinical history is fully adequate for a
      diagnosis of migraine. Patients usually perform many useless instrumental and
      laboratoristic exams and specialistic evaluations. In particular,
      electroencephalogram (EEG) is often prescribed as a first-line study in migraine
      patients. The objective is to analyze the indications of EEG in migraine and to
      evaluate whether its performance may negatively influence the time necessary to
      obtain a correct diagnosis. In particular, we compared the effects of EEG
      performance with those related to neuroradiological examinations in terms of time
      necessary to obtain a migraine diagnosis. 400 consecutive patients affected by
      migraine without aura were enrolled. Demographic and clinical data were
      collected. We used an ordinal regression model considering diagnostic delay as
      the main outcome and EEG and radiological examinations (in particular brain CT)
      as predictors. Delay was defined as a time to diagnosis greater than 1-year. Age,
      sex, number of specialists and examinations were included in the model as
      covariates. EEG represented the most often performed non-radiologic examination
      in our sample (20 %). It was associated with a significant risk of diagnostic
      delay [OR 1.66 (95 % CI 1.65-1.66, p < 0.001)]. An appropriate workup, including
      CT scan and early referral to a headache center was the most time-saving
      approach, being associated to the lowest probability of diagnostic delay [OR 0.72
      (95 % CI 0.63-0.82, p < 0.001)]. EEG is a frequently prescribed exam in migraine.
      Our data show that it can contribute to diagnostic delay, highlighting only
      uncertain and unspecific elements. These data confirm the usefulness of a wide
      application of IHS guidelines, not recommending this exam for migraine detection.

PMID- 22644195
TI  - Detection of possible factors favouring the evolution of migraine without aura
      into chronic migraine.
AB  - In a minority of cases, the natural history of migraine without aura (MO) is
      characterised over time by its evolution into a form of chronic migraine (CM). In
      order to detect the possible factors predicting this negative evolution of MO, we
      searched in our Headache Centre files for all clinical records that met the
      following criteria: (a) first visit between 1976 and 1998; (b) diagnosis of MO or
      of common migraine at the first observation, with or without association with
      other primary headache types; (c) <15 days per month of migraine at the first
      observation; and (d) at least one follow-up visit at least 10 years after the
      first visit. The patients thus identified were then divided into two groups based
      on a favourable/steady evolution (Group A: n = 243, 195 women and 48 men) or an
      unfavourable evolution (Group B: n = 72, 62 women and 10 men) of their migraine
      over time. In the two groups, we compared various clinical parameters that were
      present at the first observation or emerged at the subsequent follow-up visits.
      The parameters that were statistically significantly more frequent in Group B-
      and can therefore be considered possible negative prognostic factors--were: (a)
      >= 10 days per month of migraine at the first observation; (b) presence of
      depression at the first visit in males; and (c) onset of depression or arterial
      hypertension after the first observation but before transformation to CM in
      females. Based on these findings, in MO patients the high frequency of migraine
      attacks, comorbidity with depression, and the tendency to develop arterial
      hypertension should require particular attention and careful management to
      prevent evolution into CM.

PMID- 22644196
TI  - Disability and mood state in patients with episodic and chronic migraine
      associated to medication overuse.
AB  - This study aims to compare disability and mood state in patients with episodic
      (EM) and chronic migraine associated to medication overuse (CM-MO), and to assess
      the relationships between the two outcomes. Patients, matched for age and gender,
      were administered the MIDAS, the WHO-DAS-2 and BDI-2. Difference between EM and
      CM-MO was assessed with the Kolmogorov-Smirnov Test; difference in distribution
      of patients with severe disability and low mood was tested with contingency
      coefficient; the correlation between MIDAS, WHO-DAS-2 and BDI-2 was tested with
      Spearman's index. Seventy patients were enrolled: CM-MO patients reported higher
      BDI-2 scores and higher MIDAS and WHO-DAS-2 scores, and were more likely to have
      severe disability and low mood state than those with EM; BDI-2 scores were
      correlated with disability scores, particularly with WHO-DAS-2. The study shows
      that disability and mood state are negatively impacted by the presence of more
      frequent headaches and by the overuse of acute medications.

PMID- 22644197
TI  - Stroke risk and migraine: near-infrared spectroscopy study.
AB  - Migraine has been associated with an increased risk for ischemic stroke. A recent
      study suggests that a generalized peripheral vasoconstriction may represent one
      possible mechanism underlying the increased risk for ischemic stroke. The aim is
      to verify the presence of cerebral arteriolar vasoconstriction during the
      interictal period of migraine with (MA+) and without aura (MA-). We studied 10
      patients with MA+ (age 39.5 +/- 12.2 years), 10 with MA- (age 40.3 +/- 10.2
      years), according to ICHD-II criteria 2004, during the interictal period of
      migraine, and 15 age- and sex-matched healthy control subjects. At rest in all
      the participants, the time-delay in millisecond (ms), between the R-wave of an
      electrocardiogram and the arterial pulse wave of cerebral microcirculation
      detected by transcranial near-infrared spectroscopy (R-APWCMtd) on the frontal
      cortex of both side, was determined to evaluate the presence of cerebral
      arteriolar vasoconstriction. The patients with migraine had a significantly
      longer R-APWCMtd than the control subjects: the patients with MA+: +38.3 ms, p <
      0.0002; the patients with MA-: +34.7 ms, p < 0.0002. Our study seems to indicate
      that the migraine is independently associated with a mild vasoconstriction of
      cerebral arterioles that may represent one possible mechanism underlying the
      increased stroke risk especially in patients with MA+.

PMID- 22644198
TI  - Implementing gnathological and neuromuscular concepts in patients with chronic
      migraine.
AB  - Temporomandibular disorders are among the potential comorbidities of migraine,
      and recent reports showed that they may have a role in promoting its progression
      into chronic migraine (CM). In order to clarify the possible role of
      neuromuscular components of the stomatognathic system in patients with CM, we
      studied 18 patients admitted as inpatients at our Headache Unit to undergo a
      withdrawal protocol for medication overuse, who underwent orthosis, after
      clinical and instrumental gnathological evaluation. They were subsequently
      evaluated after 6 months. The values of electromyographic parameters as well as
      of pain outcomes showed a significant decrease after orthosis. The implementation
      of gnathological and neuromuscular concepts can have a relevant role in the
      management of CM patients, in the contest of a multidisciplinary approach.

PMID- 22644199
TI  - SPARTACUS: underdiagnosis of chronic daily headache in primary care.
AB  - Despite the burden of chronic daily headache (CDH), general practitioners' (GPs)
      ability to recognize it is unknown. This work is a sub-study of a population
      based study investigating GPs' knowledge on their CDH patients. Patients
      diagnosed with CDH through the screening questionnaire were interviewed by their
      GPs who indicated if subjects were known as patients suffering from CDH with
      medication overuse (MO), CDH without MO, episodic headache (EH) or non-headache
      sufferers. Our study showed that 64.37 % of CDH sufferers are misdiagnosed by
      their GPs. However, overusers are better known to GPs.

PMID- 22644200
TI  - Headache at high school: clinical characteristics and impact.
AB  - Although migraine (MH) and tension type headache (TTH) are the most common and
      important causes of recurrent headache in adolescents, they are poorly understood
      and not recognized by parents and teachers, delaying the first physician
      evaluation for correct diagnosis and management. The purpose of this study is to
      assess the knowledge about headache impact among the students of a Communication
      Private High School in Rimini city, and to evaluate the main different types of
      headaches interfering with school and social day activities. A self-administered
      questionnaire interview was given to students of the last 2 years of high school;
      ten items assessed the headache experience during the prior 12 months, especially
      during school time: the features and diagnosis of headaches types (based on the
      2004 IHS criteria), precipitating factors, disability measured using the migraine
      disability assessment (MIDAS); therapeutic intervention. Out of the 60 students,
      84 % experienced recurrent headache during the last 12 months. 79 % were females,
      aged 17-20 years; a family history was present in 74 % of headache students, in
      the maternal line; 45 % of subjects were identified as having MH and 27 % TTH; 25
      % had morning headache and 20 % in the afternoon; fatigue, emotional stress and
      lack of sleep were the main trigger factors for headache, respectively in 86, 50
      and 50 % of students; 92 % of headache students could not follow the lessons,
      could not participate in exercises and physical activity because of the headache;
      none had consulted a medical doctor and the 90 % of all students had never read,
      listened or watched television about headache. This study remarks on the need to
      promote headache educational programs, starting from high school, to increase
      communication between teachers-family-physician and patient-adolescents, with the
      goal to have an early appropriate therapeutic intervention, improvement of the
      quality of life and to prevent long-term headache disease in the adult age.

PMID- 22644201
TI  - Headache in patients with idiopathic intracranial hypertension: a pilot study to
      assess applicability of ICHD-2 diagnostic criteria.
AB  - Headache is one of the most common symptoms of idiopathic intracranial
      hypertension (IIH). The aim of this study was to investigate the applicability of
      the diagnostic criteria for "Headache attributed to IIH" included in the current
      classification of headache disorders, particularly as far as the main headache
      features. A consecutive clinical series of IIH patients with demonstration of
      increased intracranial pressure by lumbar puncture in the recumbent position were
      enrolled. Among a total of 22 patients, headache was reported by 14. The
      proportion of patients reporting the main headache features required by
      diagnostic criteria were: 93 % for daily or nearly-daily occurrence; 71.5 % for
      diffuse/non-pulsating pain; 57 % for aggravation by coughing/straining. Thus,
      these three headache features, at least one of which is required for diagnosis of
      headache attributed to IIH, were present in the vast majority of our sample,
      suggesting that their inclusion should be regarded as appropriate. The analysis
      of our results may suggest possible changes in the current ICDH-2 criteria for
      headache attributed to IIH, based on the following considerations: the existence
      of remarkable differences as far as the relative frequency of each headache
      feature; the fact that diffuse and non-pulsating pain-included in the current
      classification as a single requirement-were not always found together; the high
      frequency of migrainous associated symptoms (nausea or photophobia-phonophobia
      were present in 71.5 % cases).

PMID- 22644202
TI  - Triptans: over the migraine.
AB  - Migraine is a chronic, recurrent, disabling condition that affects millions of
      people worldwide. Proper acute care treatment for migraineurs is based on
      triptans, a class of specific medications approved over 20 years ago. Triptans
      are serotonin (5-HT1B/1D) receptor agonists that are generally effective, well
      tolerated and safe. Seven triptans are available worldwide, although not all are
      available in every country, with multiple routes of administration, giving to
      doctors and patients a wide choice. Despite the similarities of the available
      triptans, pharmacological heterogeneity offers slightly different efficacy
      profiles. Triptans are not pain medications, they are abortive migraine
      medications which cannot prevent migraines. In addition to migraine attacks,
      triptans are also helpful for cluster headaches. If they are useful in other
      primary headaches rather than migraine and cluster headache it is yet to be
      addressed. In the literature there are only limited controlled clinical data to
      support a migraine-selective activity for triptans. Reports are available about
      efficacy of triptans to stop attacks of other types of primary headache, such as
      tension type headache, hypnic headache and other rare forms of primary headaches.
      On the other hand, sumatriptan failed to treat the indomethacin-responsive
      primary headache disorders like chronic paroxysmal hemicrania and hemicrania
      continua, nor was it effective in the myofascial temporal muscle pain or in
      atypical facial pain. Why triptans are effective in so different types of primary
      headaches remain unclear. Up to date, it is not clear whether the antimigrainous
      activity of the triptans involves an action only in the periphery or in the CNS
      as well. Probably we should consider triptans as "pain killers" and not only as
      "migraine killers". We clearly need additional studies on triptans as putative
      analgesics in well-accepted animal and clinical models of acute and chronic
      somatic pain.

PMID- 22644203
TI  - Possible correlations between blood pressure, primary headaches and cutaneous
      allodynia.
AB  - Following an allostatic perspective, episodic migraine (M) may be considered as
      an adaptive behavioural response to endogenous or exogenous stressors, while its
      progression to a daily or nearly daily form (chronic migraine) may represent the
      failure of adaptive strategies. Multiple factors may enhance the
      progression/chronification of M, and among these the presence of cutaneous
      allodynia (CA) as well as alterations in blood pressure and in sleep. The working
      hypothesis of the study was that subjects with M, and particularly those with CA,
      could show a tendency towards high blood pressure levels and/or to alterations in
      the circadian rhythm of blood pressure. We studied 235 subjects consecutively
      attending a centre for blood pressure control for a blood pressure 24 h
      monitoring. Headache diagnosis was made according to the ICHD-II criteria. The
      presence of CA was evaluated through a semi-structured ad hoc questionnaire.
      Blood pressure 24 h monitoring was performed by an ambulatory blood pressure
      monitor (Space Labs) with its ad hoc software. Seventy-eight subjects had a
      history of headache (mean age 54.0 +/- 12.4 years, 18 men and 60 women); 56 of
      them had M, 22 had tension-type headache; among them, CA was found in 24/56
      subjects with M, and in 6/22 with tension-type headache; 157 subjects did not
      suffer from headache (mean age 60.5 +/- 11.5 years, 99 men and 58 women). No
      significant difference was observed between headache subjects and subjects
      without headache in terms of mean systolic and diastolic pressure, neither in the
      M nor in tension-type subgroups. With regard to the circadian rhythm of blood
      pressure, the physiological reduction during night (dipping) was more evident
      among headache subjects than in subjects without headache; this border-line
      difference was more strongly significant in subjects with CA than both non
      headache (p = 0.003) and non-CA (p = 0.05) ones. The difference between allodynic
      and non-allodynic subjects was present also in the M sub-group (7 dippers out of
      32 non-allodynic migraineurs vs. 12 dippers out of 24 allodynic migraineurs, p =
      0.03) notwithstanding the reduction of the sample size. Despite the initial
      hypothesis, subjects with primary headaches did not show differences in terms of
      mean blood pressure values and they showed a more physiologic blood pressure
      daily rhythm than those without headaches. Also the presence of CA, a marker of
      progression to chronic headache forms, was associated neither with hypertension
      nor with increased frequency of loss of dipping. M, particularly when associated
      with allodynia, may improve breathing during nocturnal sleep and consequently
      counteract possible blood pressure alterations, suggesting an allostatic function
      of allodynic headache.

PMID- 22644204
TI  - Alcohol as a dietary trigger of primary headaches: what triggering site could be
      compatible?
AB  - Alcoholic drinks (AD) have been known as migraine triggers in about one-third of
      migraine patients in retrospective studies. We have reviewed the studies
      concerning the role of AD in triggering the various types of primary headaches
      published after the International Headache Society classification of 1988. There
      are many studies showing that AD are triggers of migraine without aura (MO),
      migraine with aura (MA), cluster headache (CH) and tension-type headache (TH).
      About one-third of MO and half of CH patients reported AD as trigger factors.
      Some studies show that AD are triggers in MA and TH in a similar percentage to
      that found in MO, but there are also discordant findings. There are sparse
      reports that AD are also triggers of less frequent types of primary headache such
      as familial hemiplegic migraine, hemicrania continua and paroxysmal hemicrania.
      The mechanism of alcohol-provoking headache is debated and should be compatible
      with the principal pathogenetic theories of primary headaches. If AD are capable
      of triggering practically all primary headaches, they should act at a common
      pathogenetic level. Vasodilatation is unlikely to be compatible as common
      mechanism. An action at cortical or more likely at subcortical level is
      plausible.

PMID- 22644205
TI  - Acupressure in the control of migraine-associated nausea.
AB  - Migraine is a disabling neurological disorder, aggravated by accompanying
      symptomatology, such as nausea. One of the most interesting approaches to nausea
      adopted by traditional Chinese medicine is the stimulation of the acupoint PC6
      Neiguan. Actually there are no studies in medical literature as to the efficacy
      of treating PC6 acupoint for gastrointestinal symptoms in migraine attacks. Our
      study aimed at verifying if pressure applied to the acupoint PC6 was effective on
      nausea during migraine. Forty female patients suffering from migraine without
      aura were enrolled, if nausea was always present as accompanying symptomatology
      of their migraine. The patients were treated randomly for a total of six migraine
      attacks: three with the application of a device, the Sea-Band((r)) wristband,
      which applies continual pressure to the PC6 acupoint (phase SB), and three
      without it (phase C). The intensities of nausea at the onset, at 30, 60, 120 and
      240 min were evaluated on a scale from 0 to 10. The values were always
      significantly lower in phase SB than in phase C. Also the number of patients who
      reported at least a 50 % reduction in the nausea score was significantly higher
      in phase SB than in phase C at 30, 60 and 120 min. Moreover, the consistency of
      the treatment (response in at least two out of three treated attacks) was reached
      in 28 % patients at 60 min; in 40 % at 120 min and 59 % at 240 min. Our results
      encourage the application of PC6 acupressure for the treatment of migraine
      associated nausea.

PMID- 22644206
TI  - Obsessive-compulsive aspects as predictors of poor response to treatments in
      patients with chronic migraine and medication overuse.
AB  - Patients with chronic migraine (CM) and medication overuse (MO) have a high
      frequency of psychiatric comorbidity or psychopathological traits, the presence
      of which may have important implications for the course of the CM and the MO,
      both for response to treatment and possible relapses. Overuse of symptomatic
      drugs is regarded as one of the most important risk factor for the transformation
      of episodic migraine into CM and drug-seeking tendency due to fear of headache in
      chronic migraine patients shares with obsessive-compulsive disorder (OCD) the
      compulsive quality of the behavior. Aim of this study was to review the clinical
      history of a sample of CM patients with MO in which an obsessive-compulsive trait
      was identified, performing a comparison with a sample of patients without
      obsessive-compulsive trait. We selected 14 patients with positivity to Spectrum
      Project OBS (obsessive-compulsive disorder) questionnaire and other 14 patients
      with negativity to the same tool from among a sample of patients who were
      enrolled in a previous study on the psychopathological profile of patients
      suffering from CM with MO. According to data obtained from the clinical records
      referring to the previous 5 years, patients with OBS questionnaire positivity
      showed a worse clinical course and a tendency to early relapse in MO after
      symptomatic medication withdrawal. Our results show that the comorbidity of OCD
      should be always evaluated in patients with CM and MO as it may play a relevant
      role--particularly if not treated--among the risk factors favoring the
      progression of episodic migraine to the chronic form, and/or the tendency to a
      pathological behavior that prompts the overuse of symptomatic medications.

PMID- 22644213
TI  - Preparation of short cytosine-modified oligonucleotides by nicking enzyme
      amplification reaction.
AB  - A method for enzymatic production of short (10-20 nt) cytosine-modified
      oligonucleotides was developed by nicking enzyme amplification reaction using
      Vent(exo-) polymerase, Nt.BstNBI nicking endonuclease and 5-substituted dCTP
      derivatives. The methodology including isolation was scaled up to nanomolar
      amounts and was proved to be suitable for production of diverse base-modified
      short single-stranded oligonucleotides (inaccessible by other enzymatic methods)
      that are of potential interest as labelled primers or functionalized aptamers.

PMID- 22644214
TI  - Cost of healthcare for patients with migraine in five European countries: results
      from the International Burden of Migraine Study (IBMS).
AB  - Migraine is a disabling neurological disease that affects 14.7 % of Europeans.
      Studies evaluating the economic impact of migraine are complex to conduct
      adequately and with time become outdated as healthcare systems evolve. This study
      sought to quantify and compare direct medical costs of chronic migraine (CM) and
      episodic migraine (EM) in five European countries. Cross-sectional data collected
      via a web-based survey were screened for migraine and classified as CM (>=15
      headache days/month) or EM (<15 headache days/month), and included
      sociodemographics, resource use data and medication use. Unit cost data, gathered
      using publicly available sources, were analyzed for each type of service,
      stratified by migraine status. Univariate and multivariate log-normal regression
      models were used to examine the relationship between various factors and their
      impact on total healthcare costs. This economic analysis included data from
      respondents with migraine in the UK, France, Germany, Italy, and Spain. CM
      participants had higher level of disability and more prevalent psychiatric
      disorders compared to EM. CM participants had more provider visits, emergency
      department/hospital visits, and diagnostic tests; the medical costs were three
      times higher for CM than EM. Per patient annual costs were highest in the UK and
      Spain and lower in France and Germany. CM was associated with higher medical
      resource use and total costs compared to EM in all study countries, suggesting
      that treatments that reduce headache frequency could decrease the clinical and
      economic burden of migraine in Europe. Comparing patterns of care and outcomes
      among countries may facilitate the development of more cost-effective care, and
      bring greater recognition to patients affected by migraine.

PMID- 22644215
TI  - Refining clinical features and therapeutic options of new daily persistent
      headache: a retrospective study of 63 patients in India.
AB  - The aim of this retrospective study was to provide data on the clinical features
      and treatment outcomes of patients with NDPH (fulfilling Kung et al.'s criteria).
      A total of 63 patients were observed during a 5-yr period (2007-2012). More than
      one-third (35 %) patients had migrainous features; 65 % patients fulfilled the
      ICHD-II criteria. Both groups were similar in most clinical and epidemiological
      features. However, migrainous features were more common in patients with a prior
      history of episodic migraine (though statistically not significant). After a
      median follow-up of 9 months, 37 % patients showed "excellent" response (no or
      less than 1 headache per month). Another 30 % patients had "good" response (>50 %
      reduction in headache frequency or days per month). Excellent response was more
      in patients with a history of less than 6 months duration (statistically not
      significant). Patients with a recognized trigger showed better prognosis.
      Response was better in patients who received intravenous therapy of methyl
      prednisolone and sodium valproate. We suggest prospective and controlled studies
      to confirm our observations.

PMID- 22644216
TI  - Distressed, immobilized, or lacking employer support? A sub-classification of
      acute work-related low back pain.
AB  - INTRODUCTION: One possibility for reducing the disabling effects of low back pain
      (LBP) is to identify subgroups of patients who might benefit from different
      disability prevention strategies. The aim of this study was to test the ability
      to discern meaningful patient clusters for early intervention based on self
      reported concerns and expectations at the time of an initial medical evaluation.
      METHODS: Workers seeking an initial evaluation for acute, work-related LBP (N =
      496; 58 % male) completed self-report measures comprising of 11 possible risk
      factors for chronicity of pain and disability. Outcomes of pain, function, and
      return-to-work were assessed at 3-month follow-up. A K-means cluster analysis was
      used to derive patient subgroups based on risk factor patterns, and then these
      subgroups were compared with respect to 3-month outcomes. RESULTS: Eight of the
      11 measures showed significant associations with functional recovery and return
      to-work, and these were entered into the cluster analysis. A 4-cluster solution
      met criteria for cluster separation and interpretability, and the four clusters
      were labeled: (a) minimal risk (29 %), (b) workplace concerns (26 %); (c)
      activity limitations (27 %); and (d) emotional distress (19 %). Functional
      outcomes were best in the minimal risk group, poorest in the emotional distress
      group, and intermediate in the other two groups. A global severity index at
      baseline also showed highest overall risk in the emotional distressed group.
      CONCLUSIONS: Patterns of early disability risk factors from this study suggest
      patients have differential needs with respect to overcoming emotional distress,
      resuming normal activity, and obtaining workplace support. Classifying patients
      in this manner may improve the cost-benefit of early intervention strategies to
      prevent long-term sickness absence and disability due to LBP.

PMID- 22644217
TI  - [Guideline for the prevention and early detection of breast and ovarian cancer in
      high risk patients, particularly in women from HBOC (hereditary breast and
      ovarian cancer) families].
AB  - The Austrian guideline for prevention and early detection of breast and ovarian
      cancer in high risk patients--particularly in women from hereditary breast and
      ovarian cancer families--were established with particular consideration of the
      most recent position paper of the European Society of Breast Cancer Specialists
      (EUSOMA) by the authors mentioned above. The guideline is aimed at facilitating
      and standardizing the care and early detection strategies in women with an
      elevated life time risk for breast and ovarian cancer.

PMID- 22644219
TI  - [Researcher of the month, May 2012].

PMID- 22644231
TI  - Resveratrol induces downregulation of DNA repair genes in MCF-7 human breast
      cancer cells.
AB  - To gain insights into the antitumor mechanisms of resveratrol (RES), we carried
      out a DNA microarray analysis in the breast cancer cell line MCF-7 to study the
      global gene expression profile induced by RES treatment. The mRNA expression
      level of 19 734 well-characterized human genes from MCF-7 cells was determined
      using Affymetrix microarrays under two different RES treatments: 150 MUmol/l
      (IC(50)) and 250 MUmol/l during 48 h. A total of 1211 genes were found to have
      altered mRNA expression levels of two-fold or more in the 150 MUmol/l RES-treated
      group (518 upregulated and 693 downregulated genes). However, 2412 genes were
      found to have altered expression levels of two-fold or more in the 250 MUmol/l
      RES-treated group (651 genes upregulated and 1761 downregulated). Under both
      conditions of RES treatment, several genes of mismatch repair, DNA replication,
      homologous recombination (HR), and cell cycle were strongly inhibited.
      Consistently, we found decreased protein levels of the MRN complex (MRE11-NBS1
      RAD50), an important complex of the HR DNA repair pathway. The ability to inhibit
      the expression of DNA repair genes by RES could help to overcome drug resistance
      commonly shown by transformed cells and to provide a solid basis for carrying out
      clinical trials with RES, alone or in combination with other agents, to enhance
      treatment efficacy, reduce toxicity, and overcome chemoresistance. Remarkably,
      after RES treatment, we found a decrease in NBS1 and MRE11 protein levels, two
      major proteins involved in HR, which suggests that RES could be used to sensitize
      cancer cells to cell death in combination with anticancer drugs.

PMID- 22644232
TI  - Cancer prevention in Europe:  the Mediterranean diet as a protective choice.
AB  - In the coming years, European death rates because of cancer will further decline,
      but the overall number of cases will increase, mostly as a consequence of the
      ageing of the population. The target for cancer prevention in Europe will remain
      a healthy diet and control of obesity in addition to a decrease in smoking. A
      healthy diet model in European countries is the traditional Mediterranean diet,
      which is based on abundant and variable plant foods, high consumption of cereals,
      olive oil as the main (added) fat, low intake of (red) meat and moderate
      consumption of wine. The Mediterranean diet is associated with a reduced risk of
      cardiovascular disease and cancer. The biological mechanisms for cancer
      prevention associated with the Mediterranean diet have been related to the
      favourable effect of a balanced ratio of omega 6 and omega 3 essential fatty
      acids and high amounts of fibre, antioxidants and polyphenols found in fruit,
      vegetables, olive oil and wine. The Mediterranean diet also involves a
      'Mediterranean way of drinking', that is, regular, moderate consumption of wine
      mainly with food. This pattern of drinking increases longevity, reduces the risk
      of cardiovascular disease and does not appreciably influence the overall risk of
      cancer. However, heavy alcohol drinking is associated with digestive, upper
      respiratory tract, liver and breast cancers; therefore, avoidance or restriction
      of alcohol consumption to two drinks/day in men and one drink/day in women is a
      global public health priority.

PMID- 22644233
TI  - Why do smokers quit?
AB  - Scarce information is available, particularly from Europe, on why smokers quit.
      We analyzed this issue in a large dataset of Italian ex-smokers. Six population
      based surveys on smoking were annually conducted in 2005-2010 on a representative
      sample of the Italian adult population, which included more than 3000
      participants each year. A specific question on the main reason for quitting
      smoking was answered by a total of 3075 ex-smokers (1936 men and 1139 women).
      Overall, 43.2% of ex-smokers mentioned a current health condition as the main
      reason to stop smoking, 31.9% stopped to avoid future health problems, 6.3%
      stopped because of pregnancy or child birth, 4.0% because of imposition by the
      partner/family, 3.7% because of a physician's recommendation, 3.0% because of the
      economic cost, 0.5% because of smoking bans, and 4.6% because of other reasons.
      Statistically significant differences in the motivation to quit smoking have been
      found according to sex, age, social class, and smoking history. The majority of
      ex-smokers quit because of tobacco-related health conditions. Only a minority of
      ex-smokers quit to avoid future illness. Physicians should be encouraged to
      assist smokers to quit. The current prices of cigarettes in Italy are not
      sufficiently high to discourage people from continuing smoking.

PMID- 22644234
TI  - Ecological modulation of reproductive behaviour in the peacock blenny: a mini
      review.
AB  - The inter-populational variation in the reproductive behaviour of the peacock
      blenny Salaria pavo (Risso 1810), particularly the influence of the ecologic
      environment, was reviewed in the present work. Two populations of this species
      inhabiting contrasting environments were studied: the Ria Formosa population, a
      coastal lagoon with sandy/muddy substrate located in the south of Portugal, and
      the Gulf of Trieste, an area presenting rocky substrate located in the northern
      Adriatic sea. The remarkable differences in the mating system and reproductive
      behaviour between the two populations (namely sex-role reversal and high
      frequency of alternative reproductive tactics (ARTs) at the Ria Formosa vs
      typical sex roles and low frequency of ARTs at the Gulf of Trieste) are
      interpreted as a plastic behavioural and physiological response to contrasting
      ecological conditions. Androgens, namely 11-ketotestosterone, seem to act as
      mediators of this response. The expression and activity of the enzyme aromatase
      in the brain also seems to play a key role in fine-tuning the behavioural output
      in all male morphs as well as females.

PMID- 22644235
TI  - Perceptual and motor-based responses to hand actions on objects: evidence from
      ERPs.
AB  - We carried out a study examining the electrophysiological responses when
      participants made object decisions to objects and non-objects subject to
      congruent and incongruent hand-grip actions. Despite the grip responses being
      irrelevant to the task, event-related potentials were sensitive to the handgrip.
      There were effects of grip congruency on both P1 and N1 components, over both
      posterior and motor cortices, with the effects emerging most strongly for
      familiar objects. In addition, enhanced lateralized readiness potentials were
      observed for incongruent grips. The results suggest that there are increased
      perceptual and motor-based responses to objects and object-like stimuli that are
      grasped correctly, even when the grip is irrelevant to the task. This is
      consistent with the automatic coding of potential appropriate actions based on
      visual information from objects in the environment.

PMID- 22644237
TI  - Components of the neural signal underlying congenital nystagmus.
AB  - Congenital nystagmus is an involuntary bilateral horizontal oscillation of the
      eyes that develops soon after birth. In this study, the time constants of each of
      the components of the neural signal underlying congenital nystagmus were obtained
      by time series analysis and interpreted by comparison with those of the normal
      oculomotor system. In the neighbourhood of the fixation position, the system
      generating the neural signal is approximately linear with 3 degrees of freedom.
      The shortest time constant was in the range of 7-9 ms and corresponds to a normal
      saccadic burst signal. The other stable time constant was in the range of 22-70
      ms and corresponds to the slide signal. The final time constant characterises the
      unidentified neural mechanism underlying the unstable drift component of the
      oscillation cycle and ranges between 31 and 32 ms across waveforms. The
      characterisation of this unstable time constant poses a challenge for the
      modelling of both the normal and abnormal oculomotor control system. We
      tentatively identify the unstable component with the eye position signal supplied
      to the superior colliculus in the normal eye movement system and explore some of
      the implications of this hypothesis.

PMID- 22644236
TI  - Isolating early cortical generators of visual-evoked activity: a systems
      identification approach.
AB  - The VESPA (visual-evoked spread spectrum analysis) method estimates the impulse
      response of the visual system using a continuously varying stimulus. It has been
      used recently to address both basic cognitive and neurophysiologic questions as
      well as those surrounding clinical populations. Although the components of the
      average VESPA response are highly reminiscent of the early components of the
      visual-evoked potential (VEP) when measured over midline occipital locations, the
      two responses are acquired in different ways and, thus, they cannot be regarded
      as being equivalent. To further characterize the relationship between the VESPA
      and the VEP and the generative mechanisms underlying them, we recorded EEG from
      31 subjects in response to checkerboard-based VEP and VESPA stimuli. We found
      that, across subjects, the amplitudes of the VEP C1 component and the VESPA C1
      component were highly correlated, whereas the VEP P1 and the VESPA P1 bore no
      statistical relationship. Furthermore, we found that C1 and P1 amplitudes were
      significantly correlated in the VESPA but not in the VEP. We believe these
      findings point to the presence of common generators underlying the VESPA C1 and
      the VEP C1. We argue further that the VESPA P1, in light of its strong
      relationship to the VESPA C1, likely reflects further activation of the same
      cortical generators. Given the lack of correlation between the VEP P1 and each of
      these three other components, it is likely that the underlying generators of this
      particular component are more varied and widespread, as suggested previously. We
      discuss the implications of these relationships for basic and clinical research
      using the VESPA and for the assessment of additive-evoked versus phase-reset
      contributions to the VEP.

PMID- 22644238
TI  - The effects of transcranial magnetic stimulation on vibratory-induced presynaptic
      inhibition of the soleus H reflex.
AB  - A single-pulse transcranial magnetic stimulus (TMS) may induce contraction in
      many muscles of the body at the same time. This is specially the case when using
      the double-cone coil to obtain the motor evoked potentials in leg muscles. Even
      if intensity is kept below threshold for the soleus muscle, TMS induces
      facilitation of the soleus H reflex that is separated into two phases: the first,
      peaking at 10-20 ms and the second, peaking at 70-90 ms. We investigated the
      possibility that TMS-induced facilitation of the H reflex was related, at least
      in part, to the reafferentation volley reaching the alpha motoneuron after
      synchronized contraction of other muscles in the body. To test this hypothesis,
      we examined the effects of vibration on the TMS-induced facilitation of the
      soleus H reflex. As expected, vibration applied over the triceps tendon caused a
      significant reduction in H reflex amplitude: 42.4 +/- 6.4 % of control values.
      When conditioned by TMS at intervals corresponding to the first phase, the H
      reflex was facilitated to the same extent in both conditions: with and without
      vibration. However, at intervals corresponding to the second facilitation phase,
      there was a significantly reduced facilitation with vibration. These differential
      effects of vibration on the two phases of the TMS-induced facilitation of the H
      reflex indicate a different mechanism for each facilitation phase. The first
      phase could result from direct corticospinal excitatory input, while the second
      phase might depend on inputs via Ia afferents from heteronymous muscles.

PMID- 22644257
TI  - Exploiting sparsity and low-rank structure for the recovery of multi-slice breast
      MRIs with reduced sampling error.
AB  - It has been shown that, magnetic resonance images (MRIs) with sparsity
      representation in a transformed domain, e.g. spatial finite-differences (FD), or
      discrete cosine transform (DCT), can be restored from undersampled k-space via
      applying current compressive sampling theory. The paper presents a model-based
      method for the restoration of MRIs. The reduced-order model, in which a full
      system-response is projected onto a subspace of lower dimensionality, has been
      used to accelerate image reconstruction by reducing the size of the involved
      linear system. In this paper, the singular value threshold (SVT) technique is
      applied as a denoising scheme to reduce and select the model order of the inverse
      Fourier transform image, and to restore multi-slice breast MRIs that have been
      compressively sampled in k-space. The restored MRIs with SVT for denoising show
      reduced sampling errors compared to the direct MRI restoration methods via
      spatial FD, or DCT. Compressive sampling is a technique for finding sparse
      solutions to underdetermined linear systems. The sparsity that is implicit in
      MRIs is to explore the solution to MRI reconstruction after transformation from
      significantly undersampled k-space. The challenge, however, is that, since some
      incoherent artifacts result from the random undersampling, noise-like
      interference is added to the image with sparse representation. These recovery
      algorithms in the literature are not capable of fully removing the artifacts. It
      is necessary to introduce a denoising procedure to improve the quality of image
      recovery. This paper applies a singular value threshold algorithm to reduce the
      model order of image basis functions, which allows further improvement of the
      quality of image reconstruction with removal of noise artifacts. The principle of
      the denoising scheme is to reconstruct the sparse MRI matrices optimally with a
      lower rank via selecting smaller number of dominant singular values. The singular
      value threshold algorithm is performed by minimizing the nuclear norm of
      difference between the sampled image and the recovered image. It has been
      illustrated that this algorithm improves the ability of previous image
      reconstruction algorithms to remove noise artifacts while significantly improving
      the quality of MRI recovery.

PMID- 22644256
TI  - Assessing spatial resolution versus sensitivity from laser speckle contrast
      imaging: application to frequency analysis.
AB  - For blood perfusion monitoring, laser speckle contrast (LSC) imaging is a recent
      non-contact technique that has the characteristic of delivering noise-like
      speckled images. To exploit LSC images for quantitative physiological
      measurements, we developed an approach that implements controlled spatial
      averaging to reduce the detrimental impact of the noise and improve measurement
      sensitivity. By this approach, spatial resolution and measurement sensitivity can
      be traded-off in a flexible way depending on the quantitative prospect of the
      study. As an application, detectability of the cardiac activity from LSC images
      of forearm using power spectrum analysis is studied through the construction of
      spatial activity maps offering a window on the blood flow perfusion and its
      regional distribution. Comparisons with results obtained with signals of laser
      Doppler flowmetry probes are performed.

PMID- 22644258
TI  - Insertion of benzyne into the Pd-C bond. Synthesis of unnatural amino acid
      derivatives by sequential insertion of benzyne and CO: 2,2'-functionalized
      biaryls containing alkylamino and carboxymethyl substituents. Isolation of stable
      carbopalladated-benzyne intermediates.
AB  - Reaction of ortho-palladated derivatives of phentermine and homoveratrylamine
      with benzyne allows the synthesis of enlarged eight-membered palladacycles
      resulting from the insertion of the aryne into the Pd-C bond, which subsequently
      react with CO, to render unnatural amino acid derivatives.

PMID- 22644259
TI  - The impact of individual quality of life assessment on psychosocial attention in
      patients with chest malignancies: a randomized study.
AB  - PURPOSE: The aims of this study were to investigate the impact of individual
      health-related quality of life (HRQL) evaluation on the attention towards symptom
      control and psychosocial function in advanced cancer patients. METHODS: Patients
      with advanced lung cancer or mesothelioma who attended a pulmonary oncology
      outpatient clinic were randomized to either of two strategies for HRQL
      assessment. The experimental group (EG) answered the EORTC QLQ-C30 + LC13
      questionnaire using a digital table interface, with outprint of aggregated scale
      scores presented to the consulting physician as a support for evaluation. The
      control group (CG) answered a paper version of the same questionnaire, which was
      stored for later analysis. Consultations were audio-recorded. Outcome measures
      were a quantitative content analysis of audio-recorded consultations and medical
      and psychosocial interventions abstracted from clinical records. RESULTS: One
      hundred seventy-one patients were randomized and participated in the study.
      Issues regarding emotional function were more frequently discussed during
      consultations in the EG (p < 0.05). Similarly, interventions directed to
      emotional and social concerns were more frequent in the EG (p = 0.013 and p =
      0.0036, respectively). HRQL measures over time were similar across the groups.
      CONCLUSION: Individual HRQL assessment increased the attention to psychosocial
      functioning in patients with chest malignancies.

PMID- 22644260
TI  - Activities of daily living in Greek cancer patients treated in a palliative care
      unit.
AB  - GOALS OF WORK: To assess the psychometric properties of the Activities of Daily
      Living (ADL) scale on a Greek sample of advanced cancer patients. PATIENTS AND
      METHODS: The scale was translated with the forward-backward procedure to Greek.
      The ADL scale was administered to 136 advanced cancer patients. It was
      administered twice, with a 3-day interval, to 40 (of the 136) eligible patients
      with advanced cancer to assess the scale's stability. For the assessment of
      treatment effect, the index was administered to 90 (of the 136) patients 15 days
      later. Together with the ADL scale, the patients also completed the Instrumental
      Activities of Daily Living (IADL) scale. Confirmatory factor analysis was carried
      out using the AMOS 7.0 analysis. The reliability was assessed by the internal
      consistency (Cronbach's alpha co-efficients), and test/retest (Spearman's r
      value) of the instrument. Validity was assessed with construct validity using the
      IADL scale, treatment-effect, known groups, and convergent validity. MAIN
      RESULTS: The homogeneity of the scale proved to be satisfactory (cronbach alpha =
      0.88). Overall test-retest reliability was satisfactory. Construct validity has
      shown satisfactory correlations with IADL p < 0.0005. Convergent validity and
      treatment effect were satisfactory at p < 0.0005 and p < 0.05, respectively.
      Known groups validity detected differences according to patient's performance
      status (p < 0.0005). CONCLUSIONS: The results suggest that the Greek version of
      ADL administered in cancer patients treated in a palliative care unit is a
      reliable and valid clinical instrument.

PMID- 22644261
TI  - Interaction between serotonin reuptake inhibitors, 5-HT3 antagonists, and NK1
      antagonists in cancer patients receiving highly emetogenic chemotherapy: a case
      control study.
AB  - BACKGROUND: Previous reports suggested that selective serotonin reuptake
      inhibitors (SSRI) could decrease the activity of 5-hydroxytryptamine type 3 (5
      HT3) antagonists against acute chemotherapy-induced nausea and vomiting (CINV),
      possibly through serotonin accumulation for 5-HT3 receptors. PATIENTS AND
      METHODS: Chemonaive cancer patients receiving SSRI and antiemetic agents,
      including the 5-HT3 antagonist ondansetron and the neurokinin 1 (NK1) antagonist
      aprepitant for highly emetogenic chemotherapy (etoposide-platinum), were matched
      to control patients for the following variables: age, gender, primary tumor, past
      history of gestational emesis, chronic intake of benzodiazepines and/or
      corticosteroids, chronic alcohol intake, and aprepitant use. The primary
      evaluation criterion was the occurrence of acute vomiting during the first two
      cycles of treatment. RESULTS: Forty-four patients were eligible for this
      analysis. The proportion of patients, who experienced at least one episode of
      grade >= 1 acute vomiting in patients receiving SSRI, compared to patients who
      did not, was significantly higher (59.1 vs. 22.7%, respectively, p = 0.03, odds
      ratio 4.72, 95% confidence interval 1.13-22.88). Grade >= 2 acute vomiting was
      also significantly more frequent in patients receiving SSRI, even after the
      implementation of aprepitant to antiemetic prophylaxis (41.2 vs. 5.9%, p = 0.04).
      CONCLUSIONS: Our findings reinforce the hypothesis that SSRI decrease the
      antiemetic activity of the 5-HT3 serotonin antagonist ondansetron, resulting in
      higher rates of acute vomiting in cancer patients despite adequate antiemetic
      prophylaxis. Adding the NK1 antagonist aprepitant do not counterbalance the
      deleterious effect of SSRI, probably due to the synergistic effects of SSRI and
      NK1 antagonists on serotonin transmission.

PMID- 22644262
TI  - Psychological and immunological characteristics of fatigued women undergoing
      radiotherapy for early-stage breast cancer.
AB  - PURPOSE: The amelioration of fatigue in radiotherapy patients is limited by an
      equivocal aetiology and uncertainty regarding who is likely to experience
      significant fatigue. The research objective was to characterise fatigue in women
      undergoing radiotherapy for breast cancer, in order to evaluate associations with
      elevations in anxiety, depression and a marker of systemic inflammation. METHODS:
      Participants comprised 100 women, diagnosed with stages 0-IIA breast cancer and
      prescribed with 40 Gy in 15 fractions over 3 weeks. Fatigue was assessed at
      baseline between 10 and 22 days before radiotherapy, after 10 and 15 fractions of
      radiotherapy and 4 weeks after the completion of radiotherapy, using the
      Functional Assessment of Chronic Illness Therapy Fatigue Subscale. Psychological
      status was self-reported using the Hospital Anxiety and Depression Scale. Sera
      concentrations of interleukin-6-soluble receptor were established via enzyme
      linked immunosorbent assay. The contributions of pretreatment factors to fatigue
      were analysed using multivariable regression. RESULTS: Thirty-eight percent of
      participants experienced significant fatigue during radiotherapy, with the
      remainder little are affected. After controlling for baseline fatigue, anxiety
      before treatment was the strongest unique predictor of subsequent fatigue. During
      radiotherapy, interleukin-6-soluble receptor was significantly elevated in the
      fatigued group compared to the non-fatigued group (p = 0.01). This association
      was not mediated by depression. CONCLUSIONS: The data are consistent with the
      concept that psychological distress prior to radiotherapy relates to a distinct
      immunological and behavioural response during radiotherapy. Patients reporting
      elevated anxiety should benefit from interventions that appropriately address the
      underlying psychological distress and have the potential to ameliorate disabling
      treatment-related fatigue.

PMID- 22644263
TI  - Surrogate decision-making in Korean patients with advanced cancer: a longitudinal
      study.
AB  - PURPOSE: Although surrogate decision-making in cancer patients is well-known, few
      studies investigating the prevalence of surrogate decision-making over time have
      been reported. The objectives of this study were to investigate the level of
      surrogate decision-making in advanced cancer patients over time and the impact of
      demographic and clinical variables on surrogate decision-making. METHODS: The
      level of surrogate decision-making was measured in 572 consecutive cancer
      patients who died between January 1 and December 31, 2009. We reviewed 8,639
      informed consent forms of these patients, calculated the proportion of decisions
      made by a surrogate (PDS) for each patient, and analyzed the association of PDS
      with demographic and clinical variables. RESULTS: Surrogates completed 40.3 % of
      all consent forms. The prevalence of surrogate decision-making was higher in the
      end-of-life period (death <7 days, OR = 29.05; reference, >365 days). Surrogates
      signed consent forms more frequently for do-not-resuscitate directives, intensive
      care unit admission, emergency hemodialysis, surgery and invasive interventions
      compared with chemotherapy, radiotherapy, and diagnostic tests (OR = 3.88, P <
      0.001). Patients of older age (P = 0.036) and those with a shorter duration of
      management (P < 0.001) were independently associated with greater PDS.
      CONCLUSIONS: Surrogate decision-making was frequently observed among Korean
      cancer patients in this study, especially when the patient's death was imminent,
      and for decisions related to end-of-life care. Surrogates were also frequently
      involved in decisions for elderly or rapidly deteriorating patients. Healthcare
      professionals should consider the significant role of familial surrogates in the
      end-of-life period; comprehensive approaches are needed to preserve the best
      interest of the patients.

PMID- 22644264
TI  - Significantly higher procalcitonin levels could differentiate Gram-negative
      sepsis from Gram-positive and fungal sepsis.
AB  - Procalcitonin (PCT) levels can distinguish between infectious and non-infectious
      systemic inflammatory response. However, there are some differences between Gram
      negative (G-), Gram-positive (G+), and fungal bloodstream infections,
      particularly in different cytokine profiles, severity and mortality. The aim of
      current study was to examine whether PCT levels can serve as a distinguishing
      mark between G+, G-, and fungal sepsis as well. One hundred and sixty-six septic
      patients with positive blood cultures were examined on C-reactive protein (CRP)
      and PCT on the same date of blood culture evaluation. The median (interquartile
      range, IQR) of CRP and PCT in G+, G-, and fungal cohorts and comparison of
      measured values between groups were made using the Kruskal-Wallis test with
      subsequent Bonferroni's corrections, with p < 0.05. In 83/166 (50 %) of blood
      cultures, G+ microbes, 78/166 (47 %) G- rods, and 5/166 (3 %) fungi were
      detected. PCT concentrations (ng/ml) were significantly higher in G- compared to
      other cohorts: 8.90 (1.88; 32.60) in G-, 0.73 (0.22; 3.40) in G+, and 0.58 (0.35;
      0.73) in fungi (p < 0.00001). CRP concentrations did not differ significantly in
      groups. Significantly higher PCT levels could differentiate G- sepsis from G+ and
      fungemia. In contrast to CRP, PCT is a good discriminative biomarker in different
      bloodstream infections.

PMID- 22644266
TI  - Simultaneous determination of global DNA methylation and hydroxymethylation
      levels by hydrophilic interaction liquid chromatography-tandem mass spectrometry.
AB  - Methylation of DNA at the 5-position of cytosine (Cyt) is a well-studied
      epigenetic pathway implicated in gene silencing and embryogenesis. Recently, in
      addition to 5-methylcytosine (5mC), substantial amounts of 5
      hydroxymethylcytosine (5hmC) have been detected in certain mammalian tissues.
      Here, we developed and validated a hydrophilic interaction liquid chromatography
      tandem mass spectrometry (HILIC-MS/MS) method for the simultaneous determination
      of Cyt, 5mC, and 5hmC levels in biological samples. DNA was extracted with phenol
      chloroform, hydrolyzed using 88% formic acid at 140  degrees C, separated using a
      bridged ethylene hybrid HILIC column, and analyzed by tandem MS. The linearity
      was established over the concentration range of 1 to 500 ng/mL for Cyt, 0.2 to
      100 ng/mL for 5mC, and 0.1 to 50 ng/mL for 5hmC, and the correlation coefficients
      were all >0.99. Limits of detection were 1 pg/mL for Cyt, 45 pg/mL for 5mC, and
      57 pg/mL for 5hmC, and the limit of quantification values for Cyt, 5mC, and 5hmC
      were 2 pg/mL, 90 pg/mL, and 100 pg/mL, respectively. The relative standard
      deviation (RSD) of the intraday precision ranged from 1.87% to 4.84% and the
      interday precision from 2.69% to 4.98%. The recovery of the method varied from
      88.25% to 104.39%. The method was then applied to the analysis of DNA from
      biological samples, establishing its potential for helping researchers understand
      the roles of modified nucleobases in DNA.

PMID- 22644265
TI  - The development of a high-content screening binding assay for the smoothened
      receptor.
AB  - In this study, the development of an image-based high-content screening (HCS)
      binding assay for the seven-transmembrane (7TM) receptor Smoothened (Smo) is
      described. Using BacMam-based gene delivery of Smo, BODIPY-cyclopamine as a
      fluorescent probe, and a confocal imaging system, a robust 384-well assay that
      could be used for high-throughput compound profiling activities was developed.
      The statistically robust HCS binding assay was developed through optimization of
      multiple parameters, including cell transduction conditions, Smo expression
      levels, the image analysis algorithm, and staining procedures. Evaluation of
      structurally diverse compounds, including functional Smo activators, inhibitors,
      and related analogs, demonstrated good compound potency correlations between high
      content imaging binding, membrane fluorescence polarization binding, and gene
      reporter assays. Statistical analysis of data from a screening test set of
      compounds at a single 10-uM concentration suggested that the high-content imaging
      Smo binding assay is amenable for use in hit identification. The 384-well HCS
      assay was rapidly developed and met statistical assay performance targets, thus
      demonstrating its utility as a fluorescent whole-cell binding assay suitable for
      compound screening and profiling.

PMID- 22644267
TI  - An investigation of the bioactivation potential and metabolism profile of
      Zebrafish versus human.
AB  - The zebrafish model has been increasingly explored as an alternative model for
      toxicity screening of pharmaceutical drugs. However, little is understood about
      the bioactivation of drug to reactive metabolite and phase I and II metabolism of
      chemical in zebrafish as compared with human. The primary aim of our study was to
      establish the bioactivation potential of zebrafish using acetaminophen as a probe
      substrate. Our secondary aim was to perform metabolite profiling experiments on
      testosterone, a CYP3A probe substrate, in zebrafish and compare the metabolite
      profiles with that of human. The glutathione trapping assay of N-acetyl-p
      benzoquinone imine demonstrated that zebrafish generates the same reactive
      metabolite as humans from the bioactivation of acetaminophen. Zebrafish possesses
      functional CYP3A4/5-like and UDP-glucuronosyltransferase metabolic activities on
      testosterone. Differential testosterone metabolism was observed among the two
      species. In silico docking studies suggested that the zebrafish CYP3A65 was
      responsible for the bioactivation of acetaminophen and phase I hydroxylation of
      testosterone. Our findings reinforce the need to further characterize the drug
      metabolism phenotype of zebrafish before the model can fully achieve its
      potential as an alternative toxicity screening model in drug research.

PMID- 22644268
TI  - Identification of Rift Valley fever virus nucleocapsid protein-RNA binding
      inhibitors using a high-throughput screening assay.
AB  - Rift Valley fever virus (RVFV) is an emerging infectious pathogen that causes
      severe disease in humans and livestock and has the potential for global spread.
      Currently, there is no proven effective treatment for RVFV infection, and there
      is no licensed vaccine. Inhibition of RNA binding to the essential viral
      nucleocapsid (N) protein represents a potential antiviral therapeutic strategy
      because all of the functions performed by N during infection involve RNA binding.
      To target this interaction, we developed a fluorescence polarization-based high
      throughput drug-screening assay and tested 26 424 chemical compounds for their
      ability to disrupt an N-RNA complex. From libraries of Food and Drug
      Administration-approved drugs, druglike molecules, and natural product extracts,
      we identified several lead compounds that are promising candidates for medicinal
      chemistry.

PMID- 22644269
TI  - A homogeneous HTRF assay for the identification of inhibitors of the TWEAK-Fn14
      protein interaction.
AB  - The TWEAK-Fn14 pathway is upregulated in models of inflammation, autoimmune
      diseases, and cancer. Both TWEAK and Fn14 show increased expression also in the
      CNS in response to different stimuli, particularly astrocytes, microglia, and
      neurons, leading to activation of NF-kappaB and release of proinflammatory
      cytokines. Although neutralizing antibodies against these proteins have been
      shown to have therapeutic efficacy in animal models of inflammation, no small
      molecule therapeutics are yet available. Here, we describe the development of a
      novel homogeneous time-resolved fluorescence (HTRF)-based screening assay
      together with several counterassays for the identification of small-molecule
      inhibitors of this protein-protein interaction. Recombinant HIS-TWEAK and Fn14-Fc
      proteins as well as FLAG-TWEAK and Fn14-FLAG proteins and an anti-Fn14 antibody
      were used to establish and validate these assays and to screen a library of 60
      000 compounds. Two HTRF counterassays with unrelated proteins in the same assay
      format, an antiaggregation assay and a redox assay, were applied to filter out
      potential false-positive compounds. The novel assay and associated screening
      cascade should be useful for the discovery of small-molecule inhibitors of the
      TWEAK-Fn14 protein interaction.

PMID- 22644283
TI  - Impact of diverting general practitioner's after-hour calls to emergency medical
      dispatch centers in patients with acute myocardial infarction.
AB  - OBJECTIVE: The aim of this study was to analyze the impact of diverting off-hour
      calls to Emergency Medical Dispatch Centers (EMDC) on time delays and
      revascularization procedures for patients with ST-segment elevation myocardial
      infarction (STEMI) in a French region. METHODS: A total of 3376 consecutive
      patients admitted for acute STEMI were included from the RICO survey (a French
      regional survey for acute myocardial infarction). Patients were retrospectively
      classified into two groups: before (2001-2004) and after EMDC (2005-2008)
      implementation and followed up for mortality as primary outcomes. In addition, we
      examined the impact of the diversion on the delay to definitive care. RESULTS:
      During the study, 1781 (53%) patients were evaluated before and 1595 (47%) after
      the EMDC implementation. Access to healthcare facilities was similar for the two
      groups. The rate of off-hour calls remained stable over time. The median delay
      from first medical intervention to hospital admission decreased from 75 to 60
      min. The off-hour median interval from door to primary percutaneous coronary
      intervention dropped from 152 to 98 min. The multivariate analyses showed that
      EMDC implementing reduced preadmission delays even when adjusting for potential
      confounders. Moreover, EMDC implementing was associated with a fall in 30-day
      mortality by 60% in patients admitted during off hours and undergoing primary
      percutaneous coronary intervention (10 vs. 4%). CONCLUSION: In a real world
      setting, improving the quality of prehospital organization was effective not only
      on reducing delays but also on improving access to revascularization. Our results
      showed the beneficial impact of EMDC implementing on management of STEMI.

PMID- 22644284
TI  - Electroencephalographic findings in consecutive emergency department patients
      with altered mental status:  a preliminary report.
AB  - Electroencephalography (EEG) can help narrow the differential diagnosis of
      altered mental status (AMS) and is necessary to diagnose nonconvulsive seizure
      (NCS). The objective of this prospective observational study is to identify the
      prevalence of EEG abnormalities in emergency department patients with AMS.
      Patients of at least 13 years of age with AMS were enrolled, whereas those with
      an easily identifiable cause (e.g. hypoglycemia) underlying their AMS were
      excluded. Easily identifiable cause of AMS (e.g. hypoglycemia). A 30-min EEG with
      the standard 19 electrodes was performed on each patient. Descriptive statistics
      (%, 95% confidence interval) are used to report EEG findings of the first 50
      enrolled patients. Thirty-five EEGs (70%, 57-81%) were abnormal. The most common
      abnormality was slowing of background activities (46%, 33-60%), reflecting an
      underlying encephalopathy. NCS was diagnosed in three (6%, 1-17%), including one
      patient in nonconvulsive status epilepticus. Nine patients (18%, 10-31%) had
      interictal epileptiform abnormalities, indicating an increased risk of
      spontaneous seizure. Patients presenting to the emergency department with AMS
      have a high prevalence of EEG abnormalities, including NCS.

PMID- 22644285
TI  - Continuous occurrence of intra-individual chromosome rearrangements in the peach
      potato aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae).
AB  - Analysis of the holocentric mitotic chromosomes of the peach-potato aphid, Myzus
      persicae (Sulzer), from clones labelled 50, 51 and 70 revealed different
      chromosome numbers, ranging from 12 to 14, even within each embryo, in contrast
      to the standard karyotype of this species (2n = 12). Chromosome length
      measurements, combined with fluorescent in situ hybridization experiments, showed
      that the observed chromosomal mosaicisms are due to recurrent fragmentations of
      chromosomes X, 1 and 3. Contrary to what has generally been reported in the
      literature, X chromosomes were frequently involved in recurrent fragmentations,
      in particular at their telomeric ends opposite to the nucleolar organizer region.
      Supernumerary B chromosomes have been also observed in clones 50 and 51. The
      three aphid clones showed recurrent fissions of the same chromosomes in the same
      regions, thereby suggesting that the M. persicae genome has fragile sites that
      are at the basis of the observed changes in chromosome number. Experiments to
      induce males also revealed that M. persicae clones 50, 51 and 70 are obligately
      parthenogenetic, arguing that the reproduction by apomictic parthenogenesis
      favoured the stabilization and inheritance of the observed chromosomal fragments.

PMID- 22644293
TI  - Phase II study of NGR-hTNF in combination with doxorubicin in relapsed ovarian
      cancer patients.
AB  - BACKGROUND: The NGR-hTNF (asparagine-glycine-arginine-human tumour necrosis
      factor) is able to promote antitumour immune responses and to improve the
      intratumoural doxorubicin uptake by selectively damaging tumour blood vessels.
      METHODS: Patients progressing after >= 1 platinum/taxane-based regimen received
      NGR-hTNF 0.8 MUg m(-2) and doxorubicin 60 mg m(-2) every 3 weeks. Primary
      endpoint was a Response Evaluation Criteria in Solid Tumors-defined response rate
      with a target of more than 6 out of 37 responding patients. RESULTS: A total of
      37 patients with platinum-free interval lower than 6 months (PFI<6; n=25), or
      between 6 and 12 months (PFI=6-12; n=12) were enrolled. Median baseline
      peripheral blood lymphocyte count (PBLC) was 1.6 per ml (interquartile range, 1.2
      2.1). In all, 18 patients (49%) received more than 6 cycles. Febrile neutropaenia
      was registered in one patient (3%). Among 35 assessable patients, 8 (23%; 95% CI
      12-39%) had partial response (2 with PFI<6; 6 with PFI=6-12) and 15 (43%) had
      stable disease (10 with PFI<6; 5 with PFI=6-12). Median progression-free survival
      (PFS) was 5.0 months for all patients, 3.8 months for patients with PFI<6, and
      7.8 months for patients with PFI=6-12. Median overall survival (OS) was 17.0
      months. Patients with baseline PBLC higher than the first quartile had improved
      PFS (P=0.01) and OS (P=0.001). CONCLUSION: Tolerability and activity of this
      combination warrant further randomised testing in patients with PFI<6. The role
      of PBLC as a blood-based biomarker deserves further investigation.

PMID- 22644294
TI  - Prognosis and prognostic factors of patients with mesothelioma: a population
      based study.
AB  - BACKGROUND: It is important to regularly update survival estimates of patients
      with malignant mesothelioma as prognosis may vary according to epidemiologic
      factors and diagnostic and therapeutic management. METHODS: We assessed overall
      (baseline) survival as well as related prognostic variables in a large cohort of
      1353 patients with a confirmed diagnosis of malignant mesothelioma between 2005
      and 2008. RESULTS: About 50% of the patients were 70 years or older at diagnosis
      and the median latency time since start of asbestos exposure was 49 years. One
      year after diagnosis, 47% of the patients were alive, 20% after 2 years and 15%
      after 3 years. Prognostic variables independently associated with worse survival
      were: older age (HR=1.04 per year 95% CI (1.03-1.06)), sarcomatoid subtype
      (HR=2.45 95% CI (2.06-2.90)) and non-pleural localisation (HR=1.67 95% CI (1.26
      2.22)). CONCLUSION: Survival of patients with malignant mesothelioma is still
      limited and depends highly on patient age, mesothelioma subtype and localisation.
      In addition, a substantial part of the patients had a long latency time between
      asbestos exposure and diagnosis.

PMID- 22644295
TI  - Inhibition of transforming growth factor-beta-activated kinase-1 blocks cancer
      cell adhesion, invasion, and metastasis.
AB  - BACKGROUND: Tumour cell metastasis involves cell adhesion and invasion, processes
      that depend on signal transduction, which can be influenced by the tumour
      microenvironment. N-6 polyunsaturated fatty acids, found both in the diet and in
      response to inflammatory responses, are important components of this
      microenvironment. METHODS: We used short hairpin RNA (shRNA) knockdown of TGF
      beta-activated kinase-1 (TAK1) in human tumour cells to examine its involvement
      in fatty acid-stimulated cell adhesion and invasion in vitro. An in vivo model of
      metastasis was developed in which cells, stably expressing firefly luciferase and
      either a control shRNA or a TAK1-specific shRNA, were injected into the mammary
      fat pads of mice fed diets, rich in n-6 polyunsaturated fatty acids. Tumour
      growth and spontaneous metastasis were monitored with in vivo and in situ imaging
      of bioluminescence. RESULTS: Arachidonic acid activated TAK1 and downstream
      kinases in MDA-MB-435 breast cancer cells and led to increased adhesion and
      invasion. Knockdown of TAK1 blocked this activation and inhibited both cell
      adhesion and invasion in vitro. Tumour growth at the site of injection was not
      affected by TAK1 knockdown, but both the incidence and extent of metastasis to
      the lung were significantly reduced in mice injected with TAK1 knockdown cells
      compared with mice carrying control tumour cells. CONCLUSION: These data
      demonstrate the importance of TAK1 signalling in tumour metastasis in vivo and
      suggest an opportunity for antimetastatic therapies.

PMID- 22644297
TI  - Chromosome instability and benefit from adjuvant anthracyclines in breast cancer.
AB  - BACKGROUND: Duplication of the centromeric region of chromosome 17 (Ch17CEP) is
      associated with sensitivity to anthracyclines. An explanation may be chromosome
      instability (CIN); a frequent event in solid tumours associated with poor
      outcome. The predictive value of CIN seems to be drug dependent and CIN has been
      associated with both sensitivity and resistance to chemotherapy. METHODS: In this
      study, we used fluorescent in situ hybridisation for chromosomes 1, 7, 11, 17 and
      18 to identify patients with high tumour CIN% in 322 patients recruited into the
      BR9601 clinical trial. RESULTS: High tumour CIN% was correlated to Ch17CEP
      (P=3.68e-7) and is associated with a reduced RFS (P=0.0011) and OS (P=0.04).
      Patients with high CIN had a decreased risk of death on E-CMF compared with CMF.
      CONCLUSION: CIN is of prognostic significance and may be of predictive value in
      determining anthracycline response, although further testing is required.

PMID- 22644298
TI  - Postmenopausal endometrial cancer risk and body size in early life and middle
      age: prospective cohort study.
AB  - BACKGROUND: Greater adiposity in early life has been linked to increased
      endometrial cancer risk in later life, but the extent to which this association
      is mediated through adiposity in later life is unclear. METHODS: Among
      postmenopausal women who had never used menopausal hormone therapies and reported
      not having had a hysterectomy, adjusted relative risks (RRs) of endometrial
      cancer were estimated using Cox regression. RESULTS: Among 249 791 postmenopausal
      women with 7.3 years of follow-up on average (1.8 million person-years),
      endometrial cancer risk (n=1410 cases) was strongly associated with current body
      mass index (BMI) at baseline (RR=1.87 per 5 kg m(-2) increase in BMI, 95%
      confidence interval (CI): 1.77-1.96). Compared with women thinner than average at
      age 10, the increased risk among women plumper at age 10 (RR=1.27, 95% CI: 1.09
      1.49) disappeared after adjustment for current BMI (RR=0.90, 95% CI: 0.77-1.06).
      Similarly, compared with women with clothes size 12 or less at age 20, the
      increased risk among women with clothes size 16 or larger (RR=1.87, 95% CI: 1.61
      2.18) was not significant after adjustment for current BMI (RR=1.03, 95% CI: 0.88
      1.22). CONCLUSION: Among women who have never used hormone therapy for menopause,
      the association between body size in early life and endometrial cancer risk in
      postmenopausal women can be largely explained by women's current BMI.

PMID- 22644296
TI  - Splice variant PRKC-zeta(-PrC) is a novel biomarker of human prostate cancer.
AB  - BACKGROUND: Previously, using gene-knockdown techniques together with genome
      expression array analysis, we showed the gene protein Kinase C (PKC)-zeta (PRKCZ)
      to mediate the malignant phenotype of human prostate cancer. However, according
      to NCBI, the gene has undergone several major iterations. Therefore, to
      understand the relationship between its structure and biological activities, we
      have analysed its expressed sequence in prostate cancer cell lines and tissues.
      METHODS: Transcriptome-walking and targeted PCR were used to sequence the mRNA
      transcribed from PRKCZ. Hydropathy analysis was employed to analyse the
      hypothetical protein sequence subsequently translated and to identify an
      appropriate epitope to generate a specific monoclonal antibody. RESULTS: A novel
      sequence was identified within the 3'-terminal domain of human PRKCZ that, in
      prostate cancer cell lines and tissues, is expressed during transcription and
      thereafter translated into protein (designated PKC-zeta(-PrC)) independent of
      conventional PKC-zeta(-a). The monoclonal antibody detected expression of this 96
      kD protein only within malignant prostatic epithelium. INTERPRETATION:
      Transcription and translation of this gene sequence, including previous intronic
      sequences, generates a novel specific biomarker of human prostate cancer. The
      presence of catalytic domains characteristic of classic PKC-beta and atypical PKC
      iota within PKC-zeta(-PrC) provides a potential mechanism for this PRKCZ variant
      to modulate the malignant prostatic phenotype out-with normal cell-regulatory
      control.

PMID- 22644299
TI  - An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer.
AB  - BACKGROUND: Urinary biomarkers are needed to improve the care and reduce the cost
      of managing bladder cancer. Current biomarkers struggle to identify both high and
      low-grade cancers due to differing molecular pathways. Changes in microRNA (miR)
      expression are seen in urothelial carcinogenesis in a phenotype-specific manner.
      We hypothesised that urinary miRs reflecting low- and high-grade pathways could
      detect bladder cancers and overcome differences in genetic events seen within the
      disease. METHODS: We investigated urinary samples (n=121) from patients with
      bladder cancer (n=68) and age-matched controls (n=53). Fifteen miRs were
      quantified using real-time PCR. RESULTS: We found that miR is stable within
      urinary cells despite adverse handling and detected differential expression of 10
      miRs from patients with cancer and controls (miRs-15a/15b/24
      1/27b/100/135b/203/212/328/1224, ANOVA P<0.05). Individually, miR-1224-3p had the
      best individual performance with specificity, positive and negative predictive
      values and concordance of 83%, 83%, 75% and 77%, respectively. The combination of
      miRs-135b/15b/1224-3p detected bladder cancer with a high sensitivity (94.1%),
      sufficient specificity (51%) and was correct in 86% of patients (concordance).
      CONCLUSION: The use of this panel in patients with haematuria would have found
      94% of urothelial cell carcinoma, while reducing cystoscopy rates by 26%.
      However, two invasive cancers (3%) would have been missed.

PMID- 22644300
TI  - Luminal membrane expression of mesothelin is a prominent poor prognostic factor
      for gastric cancer.
AB  - BACKGROUND: Mesothelin is expressed in various types of malignant tumour, and we
      recently reported that expression of mesothelin was related to an unfavourable
      patient outcome in pancreatic ductal adenocarcinoma. In this study, we examined
      the clinicopathological significance of the mesothelin expression in gastric
      cancer, especially in terms of its association with the staining pattern.
      METHODS: Tissue specimens from 110 gastric cancer patients were
      immunohistochemically examined. The staining proportion and intensity of
      mesothelin expression in tumour cells were analysed, and the localisation of
      mesothelin was classified into luminal membrane and/or cytoplasmic expression.
      RESULTS: Mesothelin was positive in 49 cases, and the incidence of mesothelin
      expression was correlated with lymph-node metastasis. Furthermore, luminal
      membrane staining of mesothelin was identified in 16 cases, and the incidence of
      luminal membrane expression was also correlated with pT factor, pStage, lymphatic
      permeation, blood vessel permeation, recurrence, and poor patient outcome.
      Multivariate analysis showed that luminal membrane expression of mesothelin was
      an independent predictor of overall patient survival. CONCLUSION: We described
      that the luminal membrane expression of mesothelin was a reliable prognostic
      factor in gastric cancer, suggesting the functional significance of membrane
      localised mesothelin in the aggressive behaviour of gastric cancer cells.

PMID- 22644301
TI  - Men with cancer change their health behaviour: a prospective study from the
      Danish diet, cancer and health study.
AB  - BACKGROUND: Health behaviour changes may improve the quality of life and survival
      among cancer survivors. We prospectively examined changes in health behaviour
      among and between men with prostate cancer (PC), men with cancers other than PC
      and cancer-free men. METHODS: We analysed data for 20 914 men (50-65 years), 426
      with cancer, and 20 488 persons who were cancer-free between baseline (1993-1997)
      and follow-up (2000-2002) in multiple linear regression models to determine
      differences in changes in body mass index (BMI) and in alcohol and tobacco
      consumption. RESULTS: Body mass index and tobacco and alcohol consumption
      decreased significantly (P<0.001) between baseline and follow-up among both men
      with cancer and cancer-free men. Men with cancers other than PC significantly
      decreased their BMI (beta=-058; 95% confidence interval (CI): -0.77, -0.40) and
      tobacco consumption (beta=-1.36; 95% CI: -2.22, -0.49) compared with cancer-free
      men and were significantly more likely to quit smoking and lose weight.
      CONCLUSION: Men with cancers other than PC decreased their tobacco consumption
      and BMI significantly more than cancer-free men. Men with cancer do change their
      health behaviour; clinicians should take this into account in planning follow-up
      care for cancer survivors.

PMID- 22644302
TI  - MET in gastric carcinomas: comparison between protein expression and gene copy
      number and impact on clinical outcome.
AB  - BACKGROUND: The aim of this study was to compare gene copy number (GCN) and
      protein expression of MET and to evaluate their prognostic roles in gastric
      carcinomas. METHODS: MET protein expression and gene amplification (GA) status
      were determined by immunohistochemistry (IHC) and silver in-situ hybridisation
      (SISH), respectively, in a large series of gastric carcinoma. RESULTS: Protein
      overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in
      10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381,
      respectively. Direct comparison revealed a significant correlation between high
      level of protein expression and increased GCN. All cases with GA showed protein
      overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could
      be categorised as GA according to the ASCO/CAP guideline for human epidermal
      growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated
      with poor prognosis. CONCLUSION: MET IHC reflects well on GA, and therefore, it
      could be a primary screening test for patient selection for anti-MET therapy if
      GA is a major determinant of drug responsiveness. Also, the prognostic role of
      MET indicates that anti-MET therapy is a very promising modality in adjuvant
      treatment for gastric cancer.

PMID- 22644303
TI  - pHH3 and survivin are co-expressed in high-risk endometrial cancer and are
      prognostic relevant.
AB  - BACKGROUND: Phosphohistone-H3 (pHH3) is a promising reliable mitotic count
      biomarker. Our purpose was to study the relationship between the novel
      proliferation marker pHH3 and the established anti-apoptotic marker survivin and
      consider their prognostic relevance in endometrial cancer. METHODS: A total of
      106 patients with endometrial cancer (type I/endometrioid, n=81; type II
      carcinomas, n=18) and simple hyperplasia without atypia (n=7) were investigated.
      pHH3 and survivin expression were assessed using immunohistochemistry from
      paraffin-embedded tissue blocks. RESULTS: A strong positive correlation was
      observed between pHH3 and survivin expression (P<0.0001). Patients with high
      grade tumours and patients with type II carcinomas expressed significantly more
      pHH3 and survivin than low grade and endometrioid tumours (P<0.0001, P<0.0001,
      P<0.0001, and P<0.0001, respectively). In univariate survival analysis,
      overexpression of pHH3 and survivin were associated with increased recurrence and
      mortality (P<0.0001, P<0.0001, P<0.0001, and P<0.0001, respectively), in the
      multivariable Cox regression analyses both pHH3 and survivin could be identified
      as independent parameters for overall survival (P=0.004, and P=0.023,
      respectively). CONCLUSION: In endometrial cancer, pHH3 and survivin were strongly
      positive correlated and were both associated with type II and high-grade tumours.
      Increasing expression levels of pHH3 and survivin were associated with adverse
      prognostic factors.

PMID- 22644304
TI  - Pair-Box (PAX8) protein-positive expression is associated with poor disease
      outcome in women with endometrial cancer.
AB  - BACKGROUND: The Pax8 transcription factor genes have a role in cell
      differentiation and cell growth, and silencing of Pax8 in cell cultures results
      in cell death. The aims of this study were to determine the expression and
      correlation of Pax8 protein with several clinicopathological variables in
      patients with endometrial cancer. METHODS: The following clinical parameters from
      229 patients were used for correlation with Pax8 expression; age, histological
      subtype, myometrial depth of invasion, lymphovascular invasion (LVI), the
      International Federation of Gynecology and Obstetrics grade, lymph nodes status,
      and disease status. RESULTS: A positive association of Pax8(+) expression was
      found with high tumour grade (P=0.002), LVI+(P=0.0186), and type II tumour
      subtype (P<0.0001) in univariate analysis. Survival analysis showed an
      association of Pax8 and 5-year overall survival probability (P=0.01486), 80.04%
      for patients with Pax8(-) and 55.59% for patients with Pax8(+). There was also an
      association of Pax8 and 5-year disease-free survival probability (P=0.02028),
      72.12% for patients with Pax8(-) vs 49.88% for patients with Pax8(+). Finally, an
      association of Pax8(+) and shorter recurrence-free survival was also found
      (P=0.00203), with 74.36% for Pax8(-) and 52.11% for Pax8(+). CONCLUSION:
      Overexpression of Pax8 protein by endometrial cancer is associated with poor
      disease outcomes. Inhibition of Pax8 may be a very attractive targeted therapy
      for selective patients.

PMID- 22644305
TI  - Methylation of the calcium channel regulatory subunit alpha2delta-3 (CACNA2D3)
      predicts site-specific relapse in oestrogen receptor-positive primary breast
      carcinomas.
AB  - BACKGROUND: Calcium is an important intracellular messenger that mediates many
      biological processes that are relevant to the malignant process. Calcium ion
      channels are key in controlling the intracellular calcium, and little is known
      about their role in human cancer. METHODS: We used qPCR and pyrosequencing to
      investigate expression and epigenetic regulation of the calcium channel
      regulatory subunit alpha(2)delta-3 (CACNA2D3) in breast cancer cell lines,
      primary cancers and metastatic lesions. RESULTS: Expression of CACNA2D3 mRNA is
      regulated in breast cancer cell lines by methylation in the CpG island located in
      the 5' regulatory region of the gene. Expression is upregulated by azacytidine
      (AZA) in cells with CpG island methylation but unaffected in cells lacking
      methylation. In primary breast carcinomas, methylation is more common in cancers,
      which subsequently relapse with loco-regional and, particularly, visceral
      metastatic disease in both oestrogen receptor-alpha (ER)-positive and -negative
      cases. Furthermore, CACNA2D3 CpG island is frequently methylated in breast cancer
      that has metastasised to the central nervous system. CONCLUSION: Methylation
      dependent transcriptional silencing of CACNA2D3 may contribute to the metastatic
      phenotype of breast cancer. Analysis of methylation in the CACNA2D3 CpG island
      may have potential as a biomarker for risk of development of metastatic disease.

PMID- 22644306
TI  - CXCR4 activation maintains a stem cell population in tamoxifen-resistant breast
      cancer cells through AhR signalling.
AB  - BACKGROUND: Tamoxifen is commonly used for breast cancer therapy. However,
      tamoxifen resistance is an important clinical problem. Continuous treatment with
      conventional therapy may contribute to cancer progression in recurring cancers
      through the accumulation of drug-resistant cancer progenitors. METHODS: To
      investigate signalling mechanisms important for the maintenance and viability of
      drug-resistant cancer progenitors, we used microarray analysis, PCR array for
      genes involved in cancer drug resistance and metabolism, flow cytometry, soft
      agar colony formation assay, in vivo tumourigenicity assay and
      immunohistochemical analysis using tamoxifen-sensitive and tamoxifen-resistant
      breast cancer MCF7 cells. RESULTS: Downregulation of CXCR4 signalling by small
      molecule antagonist AMD3100 specifically inhibits growth of progenitor cell
      population in MCF7(TAM-R) cells both in vitro and in vivo. Microarray analysis
      revealed aryl hydrocarbon receptor (AhR) signalling as one of the top networks
      that is differentially regulated in MCF7(TAM-R) and MCF7 xenograft tumours
      treated with AMD3100. Further, small molecule antagonists of AhR signalling
      specifically inhibit the progenitor population in MCF7(TAM-R) cells and growth of
      MCF7(TAM-R) xenografts in vivo. CONCLUSION: The chemokine receptor CXCR4
      maintains a cancer progenitor population in tamoxifen-resistant MCF7 cells
      through AhR signalling and could be a putative target for the treatment of
      tamoxifen-resistant breast cancers.

PMID- 22644307
TI  - Identification of differentially expressed genes according to chemosensitivity in
      advanced ovarian serous adenocarcinomas: expression of GRIA2 predicts better
      survival.
AB  - BACKGROUND: The purpose of this study was to identify genes that are
      differentially expressed in chemosensitive serous papillary ovarian carcinomas
      relative to those expressed in chemoresistant tumours. METHODS: To identify novel
      candidate biomarkers, differences in gene expression were analysed in 26 stage
      IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14
      chemoresistant tumours). We subsequently investigated the immunohistochemical
      expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas.
      RESULTS: Microarray analysis revealed a total of 57 genes that were
      differentially expressed in chemoresistant and chemosensitive tumours. Of the 57
      genes, 39 genes were upregulated and 18 genes were downregulated in
      chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1,
      GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of
      GRIA2 was validated at the protein level by immunohistochemistry, and patients
      with GRIA2 expression showed a longer progression-free and overall survival
      (P=0.051 and P=0.031 respectively). CONCLUSIONS: We found 57 differentially
      expressed genes to distinguish between chemosensitive and chemoresistant tumours.
      We also demonstrated that the expression of GRIA2 among the differentially
      expressed genes provides better prognosis of patients with advanced serous
      papillary ovarian adenocarcinoma.

PMID- 22644308
TI  - Mammographic density and molecular subtypes of breast cancer.
AB  - BACKGROUND: Gene expression profiling has led to a subclassification of breast
      cancers independent of established clinical parameters, such as the Sorlie-Perou
      subtypes. Mammographic density (MD) is one of the strongest risk factors for
      breast cancer, but it is unknown if MD is associated with molecular subtypes of
      this carcinoma. METHODS: We investigated whether MD was associated with breast
      cancer subtypes in 110 women with breast cancer, operated in Stockholm, Sweden,
      during 1994 to 1996. Subtypes were defined using expression data from HGU133A+B
      chips. The MD of the unaffected breast was measured using the Cumulus software.
      We used multinomial logistic models to investigate the relationship between MD
      and Sorlie-Perou subtypes. RESULTS: Although the distribution of molecular
      subtypes differed in women with high vs low MD, this was statistically non
      significant (P=0.249), and further analyses revealed no association between the
      MD and Sorlie-Perou subtypes as a whole, nor with individual subtypes.
      CONCLUSION: These findings suggest that although MD is one of the strongest risk
      factors for breast cancer, it does not seem to be differentially associated with
      breast cancer molecular subtypes. However, larger studies with more comprehensive
      covariate information are needed to confirm these results.

PMID- 22644309
TI  - Epidemiology of eating disorders: incidence, prevalence and mortality rates.
AB  - Eating disorders are relatively rare among the general population. This review
      discusses the literature on the incidence, prevalence and mortality rates of
      eating disorders. We searched online Medline/Pubmed, Embase and PsycINFO
      databases for articles published in English using several keyterms relating to
      eating disorders and epidemiology. Anorexia nervosa is relatively common among
      young women. While the overall incidence rate remained stable over the past
      decades, there has been an increase in the high risk-group of 15-19 year old
      girls. It is unclear whether this reflects earlier detection of anorexia nervosa
      cases or an earlier age at onset. The occurrence of bulimia nervosa might have
      decreased since the early nineties of the last century. All eating disorders have
      an elevated mortality risk; anorexia nervosa the most striking. Compared with the
      other eating disorders, binge eating disorder is more common among males and
      older individuals.

PMID- 22644310
TI  - Addressing suicidality in primary care settings.
AB  - By design or by default, primary care providers (PCPs)are frequently the vanguard
      in the fight against suicide. Recent studies have highlighted programs to improve
      screening and prevention of suicidality in the medical home, particularly among
      high-risk patients, such as adolescents, the elderly, and veterans. Increasing
      efforts are also being paid to improving the PCP's skill in assessing for
      suicidality. However, it is becoming increasingly apparent that screening alone
      will not significantly lower suicide rates until it occurs within a well
      integrated system that facilitates timely referral to more intensive mental
      health services for those patients who need them. Unfortunately, such systems are
      sorely lacking in many, if not most, areas of the USA.

PMID- 22644312
TI  - Combined investigation of bulk diffusion and surface exchange parameters of
      silver catalyst coated yttrium-doped BSCF membranes.
AB  - The combined effect of minor yttrium doping and silver catalyst deposition on the
      surface kinetics (k(chem)) and bulk diffusion (D(chem)) of BSCF
      (Ba(0.5)Sr(0.5)Co(0.8)Fe(0.2)O(3-delta)) perovskite membranes was explored using
      electrical conductivity relaxation (ECR) and validated using oxygen permeation
      measurements. Yttrium doping of BSCF to form
      Ba(0.5)Sr(0.5)Co(0.8)Fe(0.175)Y(0.025)O(3-delta) (BSCFY) improved both the
      surface exchange kinetics and the bulk diffusion by an average of 44% and 177%
      respectively, supporting improved oxygen permeation measurements. The deposition
      of a silver catalyst on BSCFY further improved the surface kinetics by 63-450% at
      intermediate operating temperatures (600-750  degrees C), and reduced the
      activation energy from 163 to 90 kJ mol(-1). Interestingly, these improvements
      did not translate into enhanced oxygen fluxes for the silver coated thicker 0.5
      and 1 mm membranes, indicating that the oxygen ion transport was limited by bulk
      diffusion. However, oxygen permeation measurements on catalyst-coated 0.3 mm
      thick membranes yielded improvements of 20-35% in the range 600-900  degrees C.
      The silver catalyst was beneficial in overcoming surface kinetic limitations for
      the thinner 0.3 mm BSCFY membranes, thus suggesting that the critical thickness
      of BSCFY membranes lies around ~0.4 mm and validating the ECR measurements.

PMID- 22644311
TI  - Behavioral disturbance in dementia.
AB  - Behavioral disturbances are frequently the most challenging manifestations of
      dementia and are exhibited in almost all people with dementia. Common behavioral
      disturbances can be grouped into four categories: mood disorders (e.g.,
      depression, apathy, euphoria); sleep disorders (insomnia, hypersomnia, night-day
      reversal); psychotic symptoms (delusions and hallucinations); and agitation
      (e.g., pacing, wandering, sexual disinhibition, aggression). They are often
      persistent, greatly diminish quality of life of patients and their family
      caregivers, cause premature institutionalization, and pose a high economic burden
      on the patient, family, and society. Behavioral disturbances can be prevented and
      treated with a multifaceted approach that supports dignity and promotes comfort
      and quality of life of persons with dementia and their family members. Management
      involves prompt treatment of reversible factors and management of symptoms using
      primarily individualized nonpharmacological interventions. Pharmacological
      interventions need to be restricted to behavioral emergencies and for short-term
      treatment of behavioral disturbances that pose imminent danger to self or others.

PMID- 22644313
TI  - The histone H1 variant accumulates in response to water stress in the drought
      tolerant genotype of Gossypium herbaceum L.
AB  - We have optimized and improved the protocol for extraction of histone proteins
      from Gossypium herbaceum. Histone proteins were isolated by acid extraction
      method and fractionation of histone proteins were performed using RP-HPLC
      (reverse-phase high performance liquid chromatography). Analysis of histones from
      drought tolerant (Vagad) and drought sensitive genotype (RAHS-14) indicated that
      the tolerant genotype Vagad encodes a 29 kDa protein. Protein sequencing on MALDI
      TOF/TOF revealed that the 29 kDA protein shared sequence similarity with another
      drought-inducible linker histone-H1.S reported in tomato. This H1.S like linker
      histone was not found in RAHS-14 in our study. We further examined the expression
      of H1 variant at the transcript and protein levels and found that it was induced
      specifically in the tolerant genotype Vagad.

PMID- 22644314
TI  - Properties of lead deposits in cell walls of radish (Raphanus sativus) roots.
AB  - Various mechanisms are involved in detoxification of heavy metals such as lead
      (Pb) in plant cells. Most of the Pb taken up by plants accumulates in their
      roots. However, the detailed properties of Pb complexes in roots remain unclear.
      We have investigated the properties of Pb deposits in root cell walls of radish
      (Raphanus sativus L.) seedlings grown on glass beads bed containing Pb pellets,
      which are the source of Pb-contamination in shooting range soils. Pb deposits
      were tightly bound to cell walls. Cell wall fragments containing about 50,000 ppm
      Pb were prepared from the roots. After extracting Pb from the cell wall fragments
      using HCl, Pb ions were recombined with the Pb-extracted cell wall fragments in a
      solution containing Pb acetate. When the cell wall fragments were treated with
      pectinase (E.C. 3.2.1.15) and were chemically modified with 1-ethyl-3
      dimethylamino-propylcarboimide, the Pb-rebinding ability of the treated cell wall
      fragments decreased. When acid-treated cell wall fragments were incubated in a
      solution containing Pb(2+) and excess amounts of a chelating agent, Pb recombined
      with the cell wall fragments were measured to estimate the affinity between
      Pb(2+) and the cell wall fragments. Our data show that Pb(2+) binds to carboxyl
      groups of cell walls. The source of the carboxyl groups is suggested to be pectic
      compounds. A stability constant of the Pb-cell wall complex was estimated to be
      about 10(8). The role of root cell walls in the mechanism underlying heavy metal
      tolerance was discussed.

PMID- 22644315
TI  - Vertical variation in leaf gas exchange parameters for a Southeast Asian tropical
      rainforest in Peninsular Malaysia.
AB  - Vertical variation in leaf gas exchange characteristics of trees grown in a
      lowland dipterocarp forest in Peninsular Malaysia was investigated. Maximum net
      photosynthetic rate, stomatal conductance, and electron transport rate of leaves
      at the upper canopy, lower canopy, and forest floor were studied in situ with
      saturated condition photosynthetic photon flux density. The dark respiration rate
      of leaves at the various heights was also studied. Relationships among gas
      exchange characteristics, and also with nitrogen content per unit leaf area and
      leaf dry matter per area were clearly detected, forming general equations
      representing the vertical profile of several important parameters related to gas
      exchange. Numerical analysis revealed that the vertical distribution of gas
      exchange parameters was well determined showing both larger carbon gain for the
      whole canopy and at the same time positive carbon gain for the leaves of the
      lowest layer. For correct estimation of gas exchange at both leaf and canopy
      scales using multi-layer models, it is essential to consider the vertical
      distribution of gas exchange parameters with proper scaling coefficients.

PMID- 22644320
TI  - Dietary patterns in relation to bone mineral density among menopausal Iranian
      women.
AB  - The association of dietary patterns and bone health is not yet well known, and
      findings from the rare previous studies conducted on this issue are
      contradictory. We assessed the dietary patterns in relation to bone mineral
      density (BMD) in a sample of menopausal Iranian women. In this cross-sectional
      study, 160 menopausal women aged 50-85 were studied and their femoral neck and
      lumbar spine BMDs were measured by dual-energy X-ray absorptiometry. Dietary
      intakes were assessed with a validated 168-item food frequency questionnaire, and
      dietary patterns were identified by a principal component factor analysis method.
      Overall, six dietary patterns emerged, two of which had a significant association
      with BMD. After adjusting for potential confounders, women who had higher scores
      for the first (high in high-fat dairy products, organ meats, red or processed
      meats and nonrefined cereals) and the second (high in French fries, mayonnaise,
      sweets and desserts and vegetable oils) dietary patterns we identified were more
      likely to have BMD below the median in the lumbar spine (odds ratio 2.29; 95 %
      confidence interval 1.05-4.96; p = 0.04) and the femoral neck (odds ratio 2.83,
      95 % confidence interval 1.31-6.09; p < 0.01), respectively, compared to women
      with lower scores. Dietary patterns abundant in foods with high content of
      saturated fatty acids (similar to factor 1) or with low density of nutrients
      (similar to factor 2) are detrimental to bone health in menopausal Iranian women.
      These findings highlight the importance of proper food selection for maintaining
      bone health.

PMID- 22644321
TI  - Early response of bone marrow osteoprogenitors to skeletal unloading and
      sclerostin antibody.
AB  - Sclerostin functions as an antagonist to Wnt signaling and inhibits bone-forming
      activity. We studied the effects of skeletal unloading and treatment with
      sclerostin antibody (Scl-Ab) on mesenchymal stem cell, osteoprogenitor and
      osteoclast precursor pools, and their relationship to bone formation and
      resorption. Male C57BL/6 mice (5-months-old) were hind limb unloaded for 1 week
      or allowed normal ambulation and treated with Scl-Ab (25 mg/kg, s.c. injections
      on days 1 and 4) or placebo. Unloading decreased the serum concentration of bone
      formation marker P1NP (-35 %), number of colony-forming units (CFU) (-38 %),
      alkaline phosphatase-positive CFUs (CFU-AP+) (-51 %), and calcified nodules (-35
      %); and resulted in a fourfold increase in the number of osteoclast precursors.
      The effects of Scl-Ab treatment on unloaded and normally loaded mice were nearly
      identical; Scl-Ab increased serum P1NP and the number of CFU, CFU-AP+, and
      calcified nodules in ex vivo cultures; and increased osteoblast and bone
      mineralizing surfaces in vivo. Although the marrow-derived osteoclast precursor
      population increased with Scl-Ab, the bone osteoclast surface did not change, and
      the serum concentration of osteoclast activity marker TRACP5b decreased. Our data
      suggest that short-term Scl-Ab treatment can prevent the decrease in
      osteoprogenitor population associated with skeletal unloading and increase
      osteoblast surface and bone mineralizing surface in unloaded animals. The
      anabolic effects of Scl-Ab treatment on bone are preserved during skeletal
      unloading. These findings suggest that Scl-Ab treatment can both increase bone
      formation and decrease bone resorption, and provide a new means for prevention
      and treatment of disuse osteoporosis.

PMID- 22644322
TI  - Endogenous estradiol and the risk of incident fracture in postmenopausal women:
      the OPUS study.
AB  - Some, but not all, studies have found that low endogenous estradiol levels in
      postmenopausal women are predictive of fractures. The aim of this study was to
      examine the roles of endogenous estradiol (E(2)), sex hormone binding globulin
      (SHBG), and dehydroepiandrosterone sulfate (DHEAS) in the prediction of incident
      vertebral and nonvertebral fractures. The study subjects were 797 postmenopausal
      women from the population-based OPUS (Osteoporosis and Ultrasound Study) study.
      Spine radiographs and dual-energy X-ray absorptiometry scans were obtained for
      all subjects at baseline and 6-year follow-up. Nonfasting blood samples were
      taken at baseline for E(2), SHBG, DHEAS, and bone turnover markers. Incident
      nonvertebral fractures were self-reported and verified; vertebral fractures were
      diagnosed at a single center from spinal radiographs. Medical and lifestyle data
      were obtained by questionnaire at each visit. Thirty-nine subjects had an
      incident vertebral fracture and 119 a nonvertebral fracture. Estradiol in the
      lowest quartile predicted vertebral fracture independent of confounders including
      age, body mass index, bone mineral density, bone turnover, fracture history, and
      use of antiresorptive therapy, with an OR of 2.97 (95 % confidence interval [CI]
      1.52-5.82) by logistic regression. A calculated free estradiol index was not a
      stronger predictor than total E(2). Higher SHBG predicted vertebral fracture
      independently of age and body mass index, but not independently of E(2), bone
      mineral density, or prevalent fracture. Low DHEAS did not predict vertebral
      fracture. Nonvertebral fractures were not predicted by any of E(2), SHBG, or
      DHEAS, either in univariate or multivariate analyses. These findings suggest that
      there may be mechanistic differences in the protective effect of E(2) at
      vertebral compared with nonvertebral sites.

PMID- 22644323
TI  - Downregulation of the inflammatory response by CORM-3 results in protective
      effects in a model of postmenopausal arthritis.
AB  - CO-releasing molecules (CORMs) are a new class of drugs able to release small
      amounts of CO in biological systems. We have shown previously that one of these
      molecules, CORM-3, exerts anti-inflammatory effects in animal models. The aim of
      this study was to assess the effects of CORM-3 on bone metabolism in a model of
      postmenopausal rheumatoid arthritis osteoporosis. Ovariectomy was followed by
      collagen-induced arthritis in female DBA-1/J mice. Animals showing arthritis on
      day 22 after immunization were then randomized into control and treatment groups.
      CORM-3 was administered at 10 mg/kg, intraperitoneally, once a day. Alendronate
      was administered at 100 MUg/kg, orally, once a day. On days 36 and 50 after
      immunization, animals were killed and tissues analyzed. The arthritic score was
      significantly reduced by CORM-3 but not by alendronate treatment.
      Histopathological analyses indicated that both compounds reduced cellular
      infiltration and cartilage degradation. Local bone erosion and reduction in
      TNFalpha levels were seen for CORM-3 on day 50 and for alendronate on day 36.
      Serum levels of COMP, IL-6, MMP-3, CTX-I, alkaline phosphatase, and osteocalcin
      were decreased by both treatments, whereas TNFalpha levels were reduced by CORM-3
      and TRAP-5b by alendronate. Micro-computed tomographic analysis showed protective
      effects on trabecular bone, which were more prominent for CORM-3 on day 36 and
      for alendronate on day 50. Our results suggest that CORMs represent a novel anti
      inflammatory strategy to counteract joint bone erosion with partial protective
      effects on systemic bone loss in postmenopausal rheumatoid arthritis.

PMID- 22644324
TI  - Targeted disruption of TGFBI in mice reveals its role in regulating bone mass and
      bone size through periosteal bone formation.
AB  - Transforming growth factor-beta induced (TGFBI) and periostin are two closely
      related proteins in structure as well as in function. A previous study found that
      periostin positively regulates bone size. Here, we hypothesize that TGFBI has a
      similar function in bone development. To test this hypothesis, we employed TGFBI
      deficient mice, which were generated by targeted disruption of the TGFBI gene. We
      bred these mice with C57BL/6J mice to generate homozygous TGFBI-deficient (TGFBI(
      /-)) mice and homozygous wild-type littermates. All mice were raised to 12 weeks
      of age. Bone mass parameters were determined by PIXImus and micro-CT, bone
      strength parameters by three-point bending, and bone formation and resorption
      parameters by histomorphometry. We found that targeted disruption of TGFBI led to
      reduced body size, bone mass, bone size, and bone strength. This indicates that,
      like periostin, TGFBI also positively regulates bone size and that changes in
      bone size affect bone strength. Furthermore, there was also a significant
      decrease in periosteal, but not endosteal, bone formation rate of cortical bone
      in TGFBI(-/-) mice, suggesting that the observed effect of TGFBI on bone mass and
      bone size was largely caused by the effect of TGFBI on periosteal bone formation.

PMID- 22644325
TI  - BMP2 differentially regulates the expression of Gremlin1 and Gremlin2, the
      negative regulators of BMP function, during osteoblast differentiation.
AB  - Bone morphogenetic proteins (BMPs) control the expressions of many genes involved
      in bone formation. On the basis of our hypothesis that BMP2 stimulation-regulated
      gene expression plays a critical role in osteoblast differentiation, we performed
      genome-wide screening of messenger RNA from BMP2-treated and -untreated C2C12
      cells using a DNA microarray technique. We found that the expressions of Gremlin1
      and Gremlin2, which are known BMP antagonists, were bidirectionally regulated by
      BMP2. Gremlin1 was down-regulated by BMP2, while Gremlin2 was up-regulated in
      both time- and dose-dependent manners. Ablation of Gremlin1 or Gremlin2 enhanced
      osteoblast differentiation induced by BMP2. On the other hand, treatment with
      recombinant Gremlin1 inhibited BMP2-induced osteoblast differentiation.
      Furthermore, treatment with Smad4 siRNA and the p38 MAPK inhibitor SB203580
      suppressed BMP2-induced Gremlin2 gene expression. The differential regulation of
      Gremlin1 and Gremlin2 gene expressions by BMP2 may explain the critical function
      of these genes during osteoblast differentiation.

PMID- 22644326
TI  - MicroRNA-125a inhibits cell growth by targeting glypican-4.
AB  - Heparan sulfate proteoglycan (HSPG), such as glypican, plays a role as a co
      receptor for growth factor to influence cells proliferation. However the
      mechanism is still vague. Micro-RNAs (miRNAs) regulate cell proliferation. Their
      capacity to direct the translation and stability of targeted transcripts can
      dramatically influence cellular physiological function. To explore how the
      function of glypican is regulated involved in cell proliferation, glypican-4 was
      chosen with a bioinformatics search identifying targeting seed sequences for miR
      125a within the 3'-untranslated regions (3'UTR). Indeed, luciferase constructs
      containing the 3'UTR of glypican-4 demonstrated around 54% less activity in miR
      125a expressing cells relative to the controls. The expression of glypican-4 at
      both the transcript and protein level was down-regulated by transition
      trasfection of miR-125a in the human embryonic kidney cell line 293T (HEK293T).
      Although cell proliferation of HEK293T was not influenced by the silence of
      glypican-4, DNA synthesis in response to FGF2 in the cells was attenuated by
      knockdown of glypican-4 using siRNA technique. Further study showed that
      phosphorylation of ERK(1/2) and AKT was suppressed by overexpressing miR-125a,
      whereas the suppressed MAPK and AKT signaling could be recovered by anti-miR-125a
      treatment. Both DNA synthesis and cell proliferation were impaired by the
      inhibitor of ERK(1/2) signaling. MTT assay demonstrated that the cell
      proliferation was impaired by miR-125a overexpression, however, rescued by anti
      miR-125a in HEK293T cells. These results disclosed new function of miR-125a by
      targeting gene glypican-4 in cell growth process and illustrated the feasibility
      of using miRNAs as a therapeutic strategy to suppress cells proliferation.

PMID- 22644328
TI  - Health impact assessment in a network of European cities.
AB  - The methodology of health impact assessment (HIA) was introduced as one of four
      core themes for Phase IV (2003-2008) of the World Health Organization European
      Healthy Cities Network (WHO-EHCN). Four objectives for HIA were set at the
      beginning of the phase. We report on the results of the evaluation of introducing
      and implementing this methodology in cities from countries across Europe with
      widely differing economies and sociopolitical contexts. Two main sources of data
      were used: a general questionnaire designed for the Phase IV evaluation and the
      annual reporting template for 2007-2008. Sources of bias included the proportion
      of non-responders and the requirement to communicate in English. Main barriers to
      the introduction and implementation of HIA were a lack of skill, knowledge and
      experience of HIA, the newness of the concept, the lack of a legal basis for
      implementation and a lack of political support. Main facilitating factors were
      political support, training in HIA, collaboration with an academic/public health
      institution or local health agency, a pre-existing culture of intersectoral
      working, a supportive national policy context, access to WHO materials about or
      expertise in HIA and membership of the WHO-EHCN, HIA Sub-Network or a National
      Network. The majority of respondents did not feel that they had had the
      resources, knowledge or experience to achieve all of the objectives set for HIA
      in Phase IV. The cities that appear to have been most successful at introducing
      and implementing HIA had pre-existing experience of HIA, came from a country with
      a history of applying HIA, were HIA Sub-Network members or had made a commitment
      to implementing HIA during successive years of Phase IV. Although HIA was
      recognised as an important component of Healthy Cities' work, the experience in
      the WHO-EHCN underscores the need for political buy-in, capacity building and
      adequate resourcing for the introduction and implementation of HIA to be
      successful. 

PMID- 22644327
TI  - Sialidase significance for cancer progression.
AB  - Aberrant glycosylation is a characteristic feature of cancer cells. In
      particular, altered sialylation is closely associated with malignant properties,
      including invasiveness and metastatic potential. To elucidate the molecular
      mechanisms underlying the aberrancy, our studies have focused on mammalian
      sialidase, which catalyzes the removal of sialic acid residues from glycoproteins
      and glycolipids. The four types of mammalian sialidase identified to date show
      altered expression and behave in different manners during carcinogenesis. The
      present review briefly summarizes results on altered expression of sialidases and
      their possible roles in cancer progression. These enzymes are indeed factors
      defining cancer malignancy and thus potential targets for cancer diagnosis and
      therapy.

PMID- 22644329
TI  - The hunger-obesity paradox: obesity in the homeless.
AB  - Despite stereotypes of the homeless population as underweight, the literature
      lacks a rigorous analysis of weight status in homeless adults. The purpose of
      this study is to present the body mass index (BMI) distribution in a large adult
      homeless population and to compare this distribution to the non-homeless
      population in the United States. Demographic, BMI, and socioeconomic variables
      from patients seen in 2007-2008 were collected from the Boston Health Care for
      the Homeless Program (BHCHP). This population was compared to non-homeless adults
      from the National Health and Nutrition Examination Survey (NHANES). Among 5,632
      homeless adults, the mean BMI was 28.4 kg/m(2) and the prevalence of obesity was
      32.3 %. Only 1.6 % of homeless adults were underweight. Compared to mean BMI in
      NHANES (28.6 kg/m(2)), the difference was not significant in unadjusted analysis
      (p = 0.14). Adjusted analyses predicting BMI or likelihood of obesity also showed
      that the homeless had a weight distribution not statistically different from the
      general population. Although underweight has been traditionally associated with
      homelessness, this study suggests that obesity may be the new malnutrition of the
      homeless in the United States.

PMID- 22644330
TI  - Physiologically based pharmacokinetics joined with in vitro-in vivo extrapolation
      of ADME: a marriage under the arch of systems pharmacology.
AB  - Classic pharmacokinetics (PK) rarely takes into account the full knowledge of
      physiology and biology of the human body. However, physiologically based PK
      (PBPK) is built mainly from drug-independent "system" information. PBPK is not a
      new concept, but it has shown a very rapid rise in recent years. This has been
      attributed to a greater connectivity to in vitro-in vivo extrapolation (IVIVE)
      techniques for predicting drug absorption, distribution, metabolism, and
      excretion (ADME) and their variability in humans. The marriage between PBPK and
      IVIVE under the overarching umbrella of "systems biology" has removed many
      constraints related to cutoff approaches on prediction of ADME. PBPK-IVIVE linked
      models have repeatedly shown their value in guiding decisions when predicting the
      effects of intrinsic and extrinsic factors on PK of drugs. A review of the
      achievements and shortcomings of the models might suggest better strategies in
      extending the success of PBPK-IVIVE to pharmacodynamics (PD) and drug safety.

PMID- 22644331
TI  - Treatment algorithms for early psoriatic arthritis: do they depend on disease
      phenotype?
AB  - Psoriatic arthritis is a distinct inflammatory arthritis associated with
      psoriasis and characterized by a broad clinical phenotype. Associated with skin
      disease, patients may have differing patterns of peripheral joint disease,
      spondyloarthritis, enthesitis, dactylitis, and nail disease with overlap and
      transition between phenotypes. Research over the past decade has resulted in a
      wealth of data to guide management, and several treatment algorithms have
      recently been published with varying emphasis on disease phenotype. This review
      discusses the incorporation of phenotype in the treatment of early disease, with
      extended discussion of current research and new concepts in disease measurement
      that will impact the development of future algorithms.

PMID- 22644332
TI  - Improving the photocatalytic performance of graphene-TiO2 nanocomposites via a
      combined strategy of decreasing defects of graphene and increasing interfacial
      contact.
AB  - Incessant interest has been shown in the synthesis of graphene (GR)-semiconductor
      nanocomposites as photocatalysts aiming to utilize the excellent electron
      conductivity of GR to lengthen the lifetime of photoexcited charge carriers in
      the semiconductor and, hence, improve the photoactivity. However, research works
      focused on investigating how to make sufficient use of the unique electron
      conductivity of GR to design a more efficient GR-semiconductor photocatalyst have
      been quite lacking. Here, we show a proof-of-concept study on improving the
      photocatalytic performance of GR-TiO(2) nanocomposites via a combined strategy of
      decreasing defects of GR and improving the interfacial contact between GR and the
      semiconductor TiO(2). The GR-TiO(2) nanocomposite fabricated by this approach is
      able to make more sufficient use of the electron conductivity of GR, by which the
      lifetime and transfer of photoexcited charge carriers of GR-TiO(2) upon visible
      light irradiation will be improved more efficiently. This in turn leads to the
      enhancement of visible-light-driven photoactivity of GR-TiO(2) toward selective
      transformation of alcohols to corresponding aldehydes using molecular oxygen as a
      benign oxidant under ambient conditions. It is anticipated that our current work
      would inform ongoing efforts to exploit the rational design of smart, more
      efficient GR-semiconductor photocatalysts for conversion of solar to chemical
      energy by heterogeneous photocatalysis.

PMID- 22644337
TI  - Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins
      (HMGB1/HMGB2) antibodies and anti-Saccharomyces cerevisiae antibodies (ASCA):
      accuracy in differentially diagnosing UC and CD and correlation with inflammatory
      bowel disease phenotype.
AB  - BACKGROUND: The development of a supportive diagnostic method has long been
      required to differentially diagnose ulcerative colitis (UC) and Crohn's disease
      (CD). Several antibodies circulate in the sera of patients with inflammatory
      bowel disease. We previously identified the high mobility group box 1 and box 2
      non-histone chromosomal proteins (HMGB1 and HMGB2) as novel antigens of
      perinuclear type anti-neutrophil cytoplasmic antibodies (pANCA) and discovered
      anti-HMGB1/HMGB2 antibodies in sera from patients with UC. Here, we evaluated the
      ability of anti-HMGB1/HMGB2 antibodies combined with anti-Saccharomyces
      cerevisiae antibodies (ASCA) to differentially diagnose UC and CD. METHODS: We
      measured titers of anti-HMGB1/HMGB2 antibodies and ASCA in the sera of 213
      patients with UC and 93 with CD, using enzyme-linked immunosorbent assays.
      RESULTS: Among the patients with UC, 26.8% were positive for anti-HMGB1/HMGB2
      antibodies, with 85.0% specificity towards CD and a positive predictive value of
      80.3%. Corticosteroids significantly suppressed the titer of anti-HMGB1/HMGB2
      antibodies. Among the patients with CD, 24.7% were positive for ASCA, with 96.2%
      specificity towards UC and a positive predictive value of 74.2%. Interestingly,
      the positivity rate of anti-HMGB/HMGB2 antibodies was higher (35.7%) in patients
      with the ileitis type of CD than in patients with CD in the colon (6.2%;
      significant difference, P < 0.01). The specificity of anti-HMGB1/HMGB2 antibodies
      in UC for CD in the colon was 93.8%. CONCLUSIONS: CD in the colon and UC can be
      differentially diagnosed using anti-HMGB/HMGB2 antibodies combined with ASCA.

PMID- 22644338
TI  - Whitepapers on imaging infrastructure for research: Part 1: General workflow
      considerations.

PMID- 22644340
TI  - An evolution model for sequence length based on residue insertion-deletion
      independent of substitution: an application to the GC content in bacterial
      genomes.
AB  - We introduce here a gene evolution model which is an extension of the time
      continuous stochastic IDIS model (Lebre and Michel in J. Comput. Biol. Chem.
      34:259-267, 2010) to sequence length. This new IDISL (Insertion Deletion
      Independent of Substitution based on sequence Length) model gives an analytical
      expression of the residue occurrence probability p(l) at sequence length l
      depending on stochastically independent processes of substitution, insertion, and
      deletion. Furthermore, in contrast to all mathematical models in this research
      field, the substitution, insertion, and deletion parameters of the IDISL model
      are independent of each other. For any diagonalizable substitution matrix M, the
      residue occurrence probability p(l) is given as a function of the eigenvalues of
      M, the eigenvector matrix of M, a vector r of the residue insertion rates, a
      deletion rate d (unlike our previous IDIS model), and a vector of the initial
      residue occurrence probability p(l(0)) at sequence length l(0).As another
      difference with the classical evolution approaches which mainly focus on sequence
      alignment, the IDIS class of models allows a mathematical analysis of the
      behavior of the residue occurrence probability according to either evolution time
      or sequence length. The length parameter can be associated with any nucleotide
      regions: genes, genomes, introns, repeats, 5' and 3' regions, etc. Three
      properties of the IDISL model are given in relation with the sequence length l:
      parameter scale, inverse evolution, and residue equilibrium distribution.
      Nucleotide occurrence probabilities are given in the particular case of the IDISL
      HKY model, i.e. the IDISL model associated with the HKY asymmetric substitution
      matrix (Hasegawa et al. in J. Mol. Evol. 22:160-174, 1985).An application of the
      IDISL model is developed for a massive statistical analysis of GC content in all
      complete bacterial genomes available to date (894 non-anaerobic and anaerobic
      genomes). The IDISL-HKY model confirms the increase of the GC content with the
      genome length for two non-anaerobic taxonomic groups of bacterial genomes.
      Moreover, the non-linear modelling proposed by the IDISL model outperforms the
      most recent modelling of GC content in these bacterial genomes (Wang et al. in
      Biochem. Biophys. Res. Commun. 342:681-684, 2006; Musto et al. in Biochem.
      Biophys. Res. Commun. 347:1-3, 2006).

PMID- 22644339
TI  - Stevioside suppressed inflammatory cytokine secretion by downregulation of NF
      kappaB and MAPK signaling pathways in LPS-stimulated RAW264.7 cells.
AB  - Stevioside, a diterpene glycoside isolated from Stevia rebaudiana, has been
      reported to have anti-inflammatory properties. However, the underlying molecular
      mechanisms are not well understood. The objective of this study was to
      investigate the molecular mechanism of stevioside in modifying lipopolysaccharide
      (LPS)-induced signal pathways in RAW264.7 cells. RAW264.7 cells were stimulated
      with LPS in the presence or absence of stevioside. The expression of pro
      inflammatory cytokines was determined by enzyme-linked immunosorbent assay and
      quantitative real-time polymerase chain reaction. Nuclear factor-kappaB (NF
      kappaB), inhibitory kappa B (IkappaBalpha) protein, p38, extracellular signal
      regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) were determined by
      western blot. The results showed that stevioside dose-dependently inhibited the
      expression of tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta
      in LPS-stimulated RAW264.7 cells. Western blot analysis showed that stevioside
      suppressed LPS-induced NF-kappaB activation, IkappaBa degradation,
      phosphorylation of ERK, JNK, and P38. Our results suggest that stevioside exerts
      an anti-inflammatory property by inhibiting the activation of NF-kappaB and
      mitogen-activated protein kinase signaling and the release of proinflammatory
      cytokines. These findings suggest that stevioside may be a therapeutic agent
      against inflammatory diseases.

PMID- 22644341
TI  - The coalescence of intrahost HIV lineages under symmetric CTL attack.
AB  - Cytotoxic T lymphocytes (CTLs) are immune system cells that are thought to play
      an important role in controlling HIV infection. We develop a stochastic ODE model
      of HIV-CTL interaction that extends current deterministic ODE models. Based on
      this stochastic model, we consider the effect of CTL attack on intrahost HIV
      lineages assuming that CTLs attack several epitopes with equal strength. In this
      setting, we introduce a limiting version of our stochastic ODE under which we
      show that the coalescence of HIV lineages can be described through Poisson
      Dirichlet distributions. Through numerical experiments, we show that our results
      under the limiting stochastic ODE accurately reflect HIV lineages under CTL
      attack when the HIV population size is on the low end of its hypothesized range.
      Current techniques of HIV lineage construction depend on the Kingman coalescent.
      Our results give an explicit connection between CTL attack and HIV lineages.

PMID- 22644342
TI  - Effects of dosing interval on the pharmacokinetic and pharmacodynamic
      interactions between the oral adsorbent AST-120 and triazolam in humans.
AB  - OBJECTIVE: The objective of this study was to evaluate the pharmacokinetic and
      pharmacodynamic interactions between the oral adsorbent AST-120 and triazolam.
      METHODS: In this randomized, cross-over study, 12 healthy volunteers received a
      single oral dose of triazolam 0.25 mg alone or with AST-120 2 g given 0, 30 or 60
      min before triazolam administration. RESULTS: The area under the plasma triazolam
      concentration-time curve (AUC(0-infinity)) significantly decreased with
      simultaneous AST-120 + triazolam (alone vs simultaneous: 10.9 +/- 6.0 vs 6.4 +/-
      2.6 ng.h/mL, p = 0.003). Triazolam-induced impairment in psychomotor performance
      assessed by the digit symbol substitution test was significantly attenuated when
      AST-120 was administered simultaneously. No significant changes in
      pharmacokinetic and pharmacodynamic parameters were observed when AST-120 was
      given 30 or 60 min before triazolam administration. CONCLUSIONS: Administering
      AST-120 simultaneously with triazolam affects the pharmacokinetics and
      pharmacodynamics of triazolam. Dosing AST-120 at least 30 min before triazolam
      administration may avoid these interactions.

PMID- 22644343
TI  - Epidemiology and potential associated risk factors of drug-related problems in
      hospitalised children in the United Kingdom and Saudi Arabia.
AB  - AIM: Drug-related problems (DRP) are "an event or circumstance involving drug
      therapy that actually or potentially interferes with the desired health outcome".
      The extent and characteristics of DRPs in children in the UK and the Kingdom of
      Saudi Arabia (KSA) are unknown. Our aim was to determine the epidemiology of and
      identify risk factors for DRPs in hospitalised children. METHODS: A prospective
      cohort study was carried out in children aged 0-18 years, admitted to the medical
      ward, paediatric intensive care unit (PICU) and neonatal intensive care unit
      (NICU) during a 3-month period in two hospitals. Patients' charts, medical
      records and laboratory data were reviewed daily to identify DRPs; their
      preventability and severity were assessed. Logistic regression was used to
      analyse the potential risk factors associated with DRP incidence. RESULTS: Seven
      hundred and thirty-seven children (median age 2.3 years, interquartile range 6
      months to 8 years, 58.1% male) were included. Three hundred and thirty-three
      patients suffered from 478 DRPs. Overall DRP incidence was 45.2% (95% CI, 41.5
      48.8); KSA (51.1%; 95% CI, 45.8-56.3), UK (39.4%; 95% CI, 34.4-44.6). Incidence
      was highest in the PICU (59.7%; 95% CI, 47.0-71.5). Dosing problems were the most
      frequently reported DRPs (n = 258, 54%). 80.3% of DRP (n = 384) cases were
      preventable; 72.2% (n = 345) of DRPs were assessed as minor; 27% (n = 129) as
      moderate. Number of prescriptions and type of admission (transferred) were
      potential risk factors for DRP occurrence in children. CONCLUSIONS: Drug-related
      problems were common in the hospitalised children in this study; the most
      frequent were dosing problems and drug choice problems; the majority of them were
      preventable. Polypharmacy and transferred admission (another hospital or ward)
      were potential risk factors. To improve prescribing practices and minimise the
      risk of DRPs in hospitalised children, paediatric pharmacology and
      pharmacotherapy are important in medical education.

PMID- 22644344
TI  - Bevacizumab treatment in hereditary hemorrhagic teleangiectasia.

PMID- 22644345
TI  - Adverse drug reactions caused by drug-drug interactions in elderly outpatients: a
      prospective cohort study.
AB  - PURPOSE: Although the prevalence of drug-drug interactions (DDIs) in elderly
      outpatients is high, many potential DDIs do not have any actual clinical effect,
      and data on the occurrence of DDI-related adverse drug reactions (ADRs) in
      elderly outpatients are scarce. This study aimed to determine the incidence and
      characteristics of DDI-related ADRs among elderly outpatients as well as the
      factors associated with these reactions. METHODS: A prospective cohort study was
      conducted between 1 November 2010 and 31 November 2011 in the primary public
      health system of the Ourinhos micro-region, Brazil. Patients aged >=60 years with
      at least one potential DDI were eligible for inclusion. Causality, severity, and
      preventability of the DDI-related ADRs were assessed independently by four
      clinicians using validated methods; data were analysed using descriptive analysis
      and multiple logistic regression. RESULTS: A total of 433 patients completed the
      study. The incidence of DDI-related ADRs was 6 % (n = 30). Warfarin was the most
      commonly involved drug (37 % cases), followed by acetylsalicylic acid (17 %),
      digoxin (17 %), and spironolactone (17 %). Gastrointestinal bleeding occurred in
      37 % of the DDI-related ADR cases, followed by hyperkalemia (17 %) and myopathy
      (13 %). The multiple logistic regression showed that age >=80 years [odds ratio
      (OR) 4.4; 95 % confidence interval (CI) 3.0-6.1, p < 0.01], a Charlson
      comorbidity index >=4 (OR 1.3; 95 % CI 1.1-1.8, p < 0.01), consumption of five or
      more drugs (OR 2.7; 95 % CI 1.9-3.1, p < 0.01), and the use of warfarin (OR 1.7;
      95 % CI1.1-1.9, p < 0.01) were associated with the occurrence of DDI-related
      ADRs. With regard to severity, approximately 37 % of the DDI-related ADRs
      detected in our cohort necessitated hospital admission. All DDI-related ADRs
      could have been avoided (87 % were ameliorable and 13 % were preventable). The
      incidence of ADRs not related to DDIs was 10 % (n = 44). CONCLUSIONS: The
      incidence of DDI-related ADRs in elderly outpatients is high; most events
      presented important clinical consequences and were preventable or ameliorable.

PMID- 22644346
TI  - Presence of erythromycin and tetracycline resistance genes in lactic acid
      bacteria from fermented foods of Indian origin.
AB  - Lactic acid bacteria (LAB) resistant to erythromycin were isolated from different
      food samples on selective media. The isolates were identified as Enterococcus
      durans, Enterococcus faecium, Enterococcus lactis, Enterococcus casseliflavus,
      Lactobacillus salivarius, Lactobacillus reuteri, Lactobacillus plantarum,
      Lactobacillus fermentum, Pediococcus pentosaceus and Leuconostoc mesenteroides.
      Of the total 60 isolates, 88 % harbored the ermB gene. The efflux gene msrA was
      identified in E. faecium, E. durans, E. lactis, E. casseliflavus, P. pentosaceus
      and L. fermentum. Further analysis of the msrA gene by sequencing suggested its
      homology to msrC. Resistance to tetracycline due to the genes tetM, tetW, tetO,
      tetK and tetL, alone or in combination, were identified in Lactobacillus species.
      The tetracycline efflux genes tetK and tetL occurred in P. pentosaceus and
      Enterococcus species. Since it appeared that LAB had acquired these genes,
      fermented foods may be a source of antibiotic resistance.

PMID- 22644347
TI  - Multidimensional free energy volumes offer unique insights into reaction
      mechanisms, molecular conformation and association.
AB  - Free energy is a central measure in statistical mechanics and the means by which
      other thermodynamic properties of a system may be accessed. Using an efficient
      numerical method referred to as the Free Energy from Adaptive Reaction Coordinate
      Forces (FEARCF) method it is shown that multidimensional free energy volumes
      (FEVs) are computable and that they are critical to the understanding of
      reactions, conformational analysis and molecular association. Specifically the
      FEV of the hydrolysis reaction catalysed by a cellobiohydrolase I is shown to
      reveal molecular details of the reaction mechanism. The reaction is understood
      from a combination of the two dimensional reaction free energy surface, W(xi(1),
      xi(2)) and the three dimensional glucopyranose ring pucker FEV, W(xi(1), xi(2),
      xi(3)). These studies provide for the first time details of the evolution of the
      oxocarbenium ion, which is a key to characterizing transition state structures
      seen in carbohydrate chemistry. A long-standing challenge has been the
      unambiguous assignment of the relative orientation of molecular pairs in
      solution. Here we describe how the molecular association of the benzene dimer in
      water and their relative orientational attraction are found from four
      dimensional, FEVs W(xi(1), xi(2), xi(3), xi(4)).

PMID- 22644348
TI  - High-calcium, vitamin D fortified milk is effective in improving bone turnover
      markers and vitamin D status in healthy postmenopausal Chinese women.
AB  - BACKGROUND/OBJECTIVES: Risk for developing osteoporosis increases in Asia. The
      purpose of the study was to evaluate the impact of a high-calcium vitamin D
      fortified milk (HCM) intervention on parathyroid hormone (PTH) levels, vitamin D
      status and markers of bone turnover in postmenopausal Chinese women.
      SUBJECTS/METHODS: Sixty three women (>55 years) were assigned to receive two
      servings of either a calcium/vitamin D fortified milk or a control drink for 12
      weeks. PTH, serum 25 (OH)D levels, C-telopeptide of type I collagen (CTX) levels
      and procollagen type I N-terminal propeptide (PINP) were measured at baseline, 2,
      8 and 12 weeks of supplementation. RESULTS: Daily calcium intake at baseline
      ranged between 260 and 482 mg for the HCM, and 252 and 692 mg for the control
      group. HCM improved serum 25 (OH)D levels significantly (33.13-39.49 nmol/l),
      while remaining similar in the control group (29.27-28.21 nmol/l). The difference
      between the groups were significant at week 2, 8 and 12. The percentage change in
      PTH levels in the HCM group was significant from week 2 onwards compared to the
      control drink (P<0.017, P<0.05 and P<0.001 at weeks 2, 8 and 12, respectively).
      Plasma CTX of the HCM group reduced by 25% between weeks 0 and 2, remaining
      significantly lower and at similar levels up to week 12. The difference between
      the HCM and control group for PINP reached significance at weeks 8 (P=0.011) and
      12 (P=0.003). CONCLUSIONS: The HCM intervention significantly improved vitamin D
      status and reduced bone turnover over 12 weeks in postmenopausal Chinese women.

PMID- 22644349
TI  - Jewish ethical themes that should inform the national healthcare discussion: a
      prolegomenon.
AB  - Despite the passage of H.R. 3590 in the 111th Congress, the national healthcare
      debate in the United States continues, with repeal or modification of the Patient
      Protection and Affordable Care Act under ongoing consideration. Reference is
      often made to morality or ethics, but typically in general terms only. This paper
      elucidates themes from one system of moral theology, namely Jewish healthcare
      ethics, that would valuably inform this debate. Themes include "covenant,"
      "holiness," "justice," "mercy," "for the sake of peace," "to save a life,"
      "peoplehood," "repair of the world," "repentance," and "jubilee." Policy-related,
      economic, political, and moral challenges to acting on these principles are
      discussed.

PMID- 22644350
TI  - Management of the cardiorenal syndrome in acute heart failure.
AB  - OPINION STATEMENT: Interactions between the heart and kidney in the setting of
      acute heart failure are complex and have a substantial impact on patient care and
      outcomes. Further research is needed to better distinguish the different causes
      of kidney injury, allow its early and accurate prediction and detection, and
      identify therapeutic targets. Novel renal biomarkers could potentially provide a
      useful tool for this purpose. Restoration of optimal fluid status and resolution
      of renal venous congestion are important goals of therapy. Changes in serum
      creatinine, although an important marker of renal function, may not be associated
      with adverse outcomes, especially if they are transient and a consequence of more
      aggressive decongestion, or the appropriate titration of drugs affecting the
      renin-angiotensin-aldosterone axis. In addition to loop diuretics, a variety of
      drugs and strategies have been investigated in acute heart failure. Use of
      mineralocorticoid receptor antagonists and vasopressin antagonists may have
      potential benefits and should be further investigated. Inotropic agents should be
      limited in those clinical settings suggesting hypoperfusion. Ultrafiltration
      seems to provide a safe and effective tool to overcome diuretic resistance and
      optimize fluid status avoiding detrimental effects of diuretic therapy.

PMID- 22644351
TI  - The role of iron, omega-3 Fatty acids, and vitamins in heart failure.
AB  - OPINION STATEMENT: The high prevalence of iron deficiency in heart failure (HF),
      its easy detection, and its rapid treatment effects with intravenous compounds
      including, among other things, improved New York Heart Association class, quality
      of life, and exercise capacity, may offer a major new addition to the treatment
      of HF. Although more research is required in HF, iron deficiency has been
      recognized as a disease for over a century and there is no question that its
      correction is desirable for improving the health and the quality of life of the
      iron-deficient patient. Iron deficiency with or without an associated anemia
      should be routinely searched for and treated in HF patients. Controlled studies
      of omega-3 fish oils suggest that they are cardioprotective in HF. They also may
      have additional value as safe and highly effective analgesics and anti
      inflammatory agents in HF patients who often cannot take traditional nonsteroidal
      agents. The American Heart Association has recently recommended use of fish
      and/or fish supplements for all patients with cardiovascular disease. However,
      practical questions remain. For example, it is not clear what the optimal ratio
      of the two major components of fish oil, eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), should be in supplements. The role of other vitamins,
      such as vitamin D, in HF remains unclear.

PMID- 22644356
TI  - Propofol attenuates angiotensin II-induced vasoconstriction by inhibiting Ca2+
      dependent and PKC-mediated Ca 2+ sensitization mechanisms.
AB  - PURPOSE: Angiotensin II (Ang II)-induced vascular contraction is mediated by
      Ca(2+)-dependent mechanisms and Ca(2+) sensitization mechanisms. The
      phosphorylation of protein kinase C (PKC) regulates myofilament Ca(2+)
      sensitivity. We have previously demonstrated that sevoflurane inhibits Ang II
      induced vasoconstriction by inhibiting PKC phosphorylation, whereas isoflurane
      inhibits Ang II-induced vasoconstriction by decreasing intracellular Ca(2+)
      concentration ([Ca(2+)](i)) in vascular smooth muscle. Propofol also induces
      vasodilation; however, the effect of propofol on PKC-mediated myofilament Ca(2+)
      sensitivity is poorly understood. The aim of this study is to determine the
      mechanisms by which propofol inhibits Ang II-induced vascular contraction in rat
      aortic smooth muscle. METHODS: An isometric force transducer was used to
      investigate the effect of propofol on vasoconstriction, a fluorometer was used to
      investigate the change in [Ca(2+)](i), and Western blot testing was used to
      analyze Ang II-induced PKC phosphorylation. RESULTS: Ang II (10(-7) M) elicited a
      transient contraction of rat aortic smooth muscle, which was associated with an
      elevation of [Ca(2+)](i). Propofol (10(-6 )M) inhibited Ang II-induced vascular
      contraction (P < 0.01) and increase in [Ca(2+)](i) (P < 0.05) in rat aortic
      smooth muscle. Ang II also induced a rapid increase in [Ca(2+)](i) in cultured
      vascular smooth muscle cells, which was suppressed by propofol (P < 0.05).
      Propofol (10(-6) M) attenuated Ang II-stimulated PKC phosphorylation (P < 0.05).
      CONCLUSION: These results suggest that the inhibitory effect of propofol on Ang
      II-induced vascular contraction is mediated by the attenuation of a Ca(2+)
      dependent pathway and Ca(2+) sensitivity through the PKC signaling pathway.

PMID- 22644357
TI  - Buprenorphine added to levobupivacaine enhances postoperative analgesia of middle
      interscalene brachial plexus block.
AB  - PURPOSE: The aim of this study was to assess whether addition of epineural
      buprenorphine prolonged postoperative analgesia of middle interscalene brachial
      plexus block (MIB) with levobupivacaine. METHODS: One hundred and fifty
      consenting adult patients, scheduled for shoulder arthroscopic surgery for a
      rotator cuff tear under MIB with 29.5 ml of 0.75 % levobupivacaine, were
      randomized to receive additionally either saline or intramuscular buprenorphine
      0.15 mg or epineural buprenorphine 0.15 mg. Onset of sensory and motor blocks,
      duration of postoperative analgesia, and consumption of postoperative analgesics
      were compared among the groups. RESULTS: There were significant (P < 0.05)
      differences in the onset and the duration of the sensory block and in the
      duration of postoperative analgesia. Duration of both sensory block and
      postoperative analgesia was longer (P < 0.05) in patients who had received
      epineural buprenorphine (856.1 +/- 215.2 and 1,049.7 +/- 242.2 min) than in
      patients who had received intramuscular buprenorphine (693.6 +/- 143.4 and 820.3
      +/- 335.3 min) or saline (488.3 +/- 137.6 and 637.5 +/- 72.1 min). Requirement of
      postoperative rescue analgesics was lower in the epineural buprenorphine group
      than in the other two groups. Few complications occurred from MIB (<1 %) and none
      from buprenorphine. CONCLUSIONS: Epineural buprenorphine prolonged postoperative
      analgesia of MIB more effectively than intramuscular buprenorphine, which
      suggests that buprenorphine acts at a peripheral nervous system site of action.

PMID- 22644358
TI  - Altered anesthetic requirements and carbon dioxide setpoint in chronic airway
      obstruction.
AB  - Accidental ingestion of a foreign body into either tracheobronchial tree or
      esophagus is not an uncommon occurrence. However, there is limited literature
      available on sequelae of post foreign body ingestion--carbon dioxide set point
      and apneic threshold due to chronic respiratory acidosis. We report a case of
      chronic airway obstruction in a 14-month-old boy with prior history of battery
      ingestion and share our experience in the management.

PMID- 22644364
TI  - Solution and nanoscale structure selection: implications for the crystal energy
      landscape of tetrolic acid.
AB  - Solution and growth effects are in many cases critical in determining which
      crystal structure (polymorph) a molecule will adopt. Contemporary crystal
      structure prediction (CSP) rarely address formation and growth in a systematic
      way, relying instead on bulk thermodynamic stabilities. In this study, it is
      shown that analysis of simulated solutions of tetrolic acid in combination with
      calculation of stabilities for nanoscale clusters cut from bulk structures can
      distinguish between four computationally predicted crystal structures, including
      the two known forms and two speculative forms, rationalizing the formation of one
      structure rather than another on grounds other than bulk lattice energies. It is
      concluded that modelling of both solution-based supramolecular species and
      nanocrystal stabilities are necessary to explain the selection of one structure
      over another during crystal formation, and that they are sufficient for the
      specific case of tetrolic acid.

PMID- 22644368
TI  - Treatment compliance in veterans administration schizophrenia spectrum patients
      treated with risperidone long-acting injectable.
AB  - Risperidone is the first of the second-generation antipsychotics available in a
      long-acting injectable form (RLAI). This form of delivery has proven efficacy and
      safety in the treatment of schizophrenia. However, outcome studies in 'real
      world' clinical samples are lacking. We carried out a retrospective study using a
      computerized repository of clinical data from eight Veterans Affairs Medical
      Centers. Compliance with outpatient medication and metabolic monitoring frequency
      was evaluated in schizophrenia spectrum patients during treatment with oral
      risperidone (RispPO) and after switch to RLAI. Propensity scores were computed
      during baseline when both groups were on RispPO, and the two groups were matched
      on propensity scores. Matching on propensity score was successful: 132 RispPO
      patients were well matched to 132 RLAI patients during the RispPO Baseline
      Period. Days until medication discontinuation were longer in the RLAI group
      (679.2+/-499.3) than the RispPO group (403.7+/-365.1, P<0.0001). Days late for
      receiving medication were significantly shorter during the RLAI treatment (5.6+/
      6.2) than the RispPO treatment (8.2+/-8.6, P<0.004). Metabolic monitoring
      frequency was significantly greater for patients switched to RLAI for patients
      maintained on RispPO treatment. Outpatient medication compliance is enhanced
      during treatment with RLAI compared with treatment with RispPO, as is the rate of
      monitoring for metabolic measures.

PMID- 22644369
TI  - Antithrombotic therapy in patients with chronic kidney disease.

PMID- 22644370
TI  - Thrombolytic therapy of acute stroke.

PMID- 22644371
TI  - Global cardiovascular health promotion and disease prevention: 2011 and beyond.

PMID- 22644372
TI  - High-pressure loculated pericardial effusion in postpericardiotomy syndrome.

PMID- 22644373
TI  - Pulseless and alive: absence of all aortic arch branches in a healthy toddler.

PMID- 22644375
TI  - Letter by Wang and Ma regarding article, "Surgery in adults with congenital heart
      disease".

PMID- 22644376
TI  - CCDC134 interacts with hADA2a and functions as a regulator of hADA2a in
      acetyltransferase activity, DNA damage-induced apoptosis and cell cycle arrest.
AB  - Human transcriptional adaptor hADA2a is an important component of the general
      control nonderepressible 5 (GCN5) histone acetyltransferase complex. Here, we
      report that coiled-coil domain containing 134 (CCDC134), a novel nuclear protein,
      binds to hADA2a and enhances the stability of the hADA2a protein in unstressed
      conditions. Furthermore, CCDC134 was found to participate in the p300/CBP
      associated factor (PCAF) complex via hADA2a and affect the histone
      acetyltransferase activity of the complex. We also found that CCDC134 increased
      the PCAF-dependent K320 acetylation of p53 and p53 protein stability in the
      presence of hADA2a overexpression. Moreover, we demonstrated the biological
      significance of the interaction between CCDC134 and hADA2a. CCDC134 showed
      obvious nuclear accumulation after ultraviolet (UV) irradiation, and the
      knockdown of endogenous CCDC134 suppressed hADA2a-induced cell apoptosis activity
      and G1/S cell cycle arrest. Together, our findings indicate that CCDC134 might
      act as a novel regulator of hADA2a, and plays roles in the PCAF complex via
      hADA2a to affect its acetyltransferase activity and UV-induced DNA damage repair.

PMID- 22644377
TI  - An apical actin-rich domain drives the establishment of cell polarity during cell
      adhesion.
AB  - One of the most important questions in cell biology concerns how cells reorganize
      after sensing polarity cues. In the present study, we describe the formation of
      an actin-rich domain on the apical surface of human primary endothelial cells
      adhering to the substrate and investigate its role in cell polarity. We used
      confocal immunofluorescence procedures to follow the redistribution of proteins
      required for endothelial cell polarity during spreading initiation. Activated
      Moesin, vascular endothelial cadherin and partitioning defective 3 were found to
      be localized in the apical domain, whereas podocalyxin and caveolin-1 were
      distributed along the microtubule cytoskeleton axis, oriented from the centrosome
      to the cortical actin-rich domain. Moreover, activated signaling molecules were
      localized in the core of the apical domain in tight association with filamentous
      actin. During cell attachment, loss of the apical domain by Moesin silencing or
      drug disruption of the actin cytoskeleton caused irregular cell spreading and
      mislocalization of polarity markers. In conclusion, our results suggest that the
      apical domain that forms during the spreading process is a structural organizer
      of cell polarity by regulating trafficking and activation of signaling proteins.

PMID- 22644378
TI  - Myogenesis and muscle regeneration.
AB  - Skeletal muscle has received much attention with regard to developmental origin,
      control of cell differentiation and regeneration. In this article, early
      landmarks in skeletal muscle research are reviewed and recent findings on
      myogenesis are addressed with particular focus on novel regulatory molecules
      including miRNAs, as well as on the topographical heterogeneity of skeletal
      muscle origin. The latter has developed into a central theme of keen interest in
      the past years, particularly since overlaps in genetic and embryological
      background between head muscle subsets and heart muscle have been described. As
      embryonic myogenesis and regenerating myofibers employ common molecules, the
      heterogeneity in embryonic sources from which skeletal muscle groups in the
      vertebrate body take origin is closely reflected by differences in the
      susceptibility to particular muscle dystrophies as well as their regeneration
      potential. In the regeneration chapter of this review the progress that has been
      made in the field of muscle stem cell biology, with special focus on the
      satellite cells, is outlined. Satellite cells are considered the most promising
      source of muscle stem cells possessing a high regenerative potential. We shall
      discuss recent insights into the heterogeneous nature of these satellite cells
      not just in terms of their expression profile but also their regeneration
      potential. Latest findings about the motility of the satellite cell shall also be
      discussed. Furthermore, we shall outline the impact of an improved understanding
      of muscle stem cells within their environment, and of satellite cells in
      particular, on efficient stem cell replacement therapies for muscular
      dystrophies, putting embryological findings and stem cell approaches into
      context.

PMID- 22644379
TI  - Smad4 disruption accelerates keratinocyte reepithelialization in murine cutaneous
      wound repair.
AB  - Keratinocyte reepithelialization is a rate-limiting event in cutaneous wound
      repair, which involves the migration and proliferation of keratinocytes to cover
      the denuded dermal surface. Transforming growth factor-beta1 (TGF-beta1) has the
      ability to induce epithelial cell migration while inhibiting proliferation, and
      controversial results have been generated regarding the effect of TGF-beta
      signaling on reepithelialization. In this study, full-thickness skin wounds were
      made in keratinocyte-specific Smad4 knockout and the control mice. The wound
      closure, reepithelialization, keratinocyte proliferation, myofibroblast numbers
      and collagen deposition of were assessed. The results showed that the
      proliferation of keratinocytes increased, which accelerated the
      reepithelialization, and led to faster wound repair in the epidermis of Smad4
      mutant mice. Upregulation of keratin 17, 14-3-3 sigma and phosphorylated AKT in
      the hyperproliferative epidermis may be correlated with the accelerated
      reepithelialization. We conclude that Smad4 plays an inhibitory role in the
      keratinocyte-mediated reepithelialization of wound healing.

PMID- 22644380
TI  - Garlic (Allium sativum) down-regulates the expression of angiotensin II AT(1)
      receptor in adrenal and renal tissues of streptozotocin-induced diabetic rats.
AB  - The up-regulation of angiotensin II AT1 receptors has been implicated as a major
      mediator in the development of hypertension and progressive nephropathy in
      experimental diabetes. In spite of the documented potential of garlic treatments
      in ameliorating diabetic complications, the possible involvement of the
      angiotensin II AT1 receptor, as a central target for the anti-diabetic potential
      of garlic, has not been explored. Three groups of rats were studied after 8 weeks
      following diabetes induction: normal, streptozotocin-induced diabetic (control
      diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven
      specificity to the AT1 receptor, as verified by western blotting, indicated in
      immunohistochemical assays that AT1 receptor labeling was significantly increased
      in adrenal and renal tissues of control diabetic rats compared to the normal
      group. The increased AT1 receptor labeling involved all cortical zones and
      medullary chromaffin cells of the adrenal gland. Except for glomerulii, increased
      AT1 receptor labeling was also evident in proximal convoluted tubules in the
      renal cortex, and all tubular segments and interstitial cells outlining the vasa
      recta bundles in the inner stripe of the outer renal medulla. Compared with
      control diabetic rats, the labeling of the AT1 receptor in the garlic-treated
      diabetic group was significantly reduced throughout adrenal and renal regions to
      levels comparable to those observed in normal rats. The capacity of garlic to
      modulate diabetes-induced AT1 receptor up-regulation may be implicated in
      reversing the detrimental consequences of excessive Ang II signaling, manifested
      by the development of hypertension and nephropathy.

PMID- 22644381
TI  - Evidence for competition between Ixodes scapularis and Dermacentor albipictus
      feeding concurrently on white-tailed deer.
AB  - Competition among ticks, and among ectoparasites generally, has rarely been
      demonstrated. Ixodes scapularis and Dermacentor albipictus are both hard ticks
      commonly found feeding on deer harvested at Letterkenny Army Depot, in south
      central Pennsylvania, USA. The two species have contrasting life histories
      resulting in D. albipictus spending notably more time on the shared host. We
      hypothesized that this would give D. albipictus an advantage in locating and
      occupying optimal attachment sites (highly vascularized areas like the head and
      ears). Ticks were collected from 224 hunter-killed deer in December 2005 and
      November 2006 to determine if there is evidence of competition for attachment
      sites when these two species concurrently infest deer. A timed sample (3 min per
      region) of representative ticks was collected from the head (ears, face and neck
      regions) and body (axillae regions). Ixodes scapularis was more abundant and
      prevalent overall than D. albipictus. Dermacentor albipictus was found almost
      exclusively on the head, whereas I. scapularis was more evenly distributed, but
      somewhat more abundant on the body than on the head. The proportion of I.
      scapularis on the head was reduced at high D. albipictus abundances, but I.
      scapularis abundance did not alter the distribution of D. albipictus. This study
      supports the hypothesis of competition for preferred attachment sites between
      these two species of ticks, and suggests that D. albipictus may be competitively
      dominant over I. scapularis on the head region of concurrently infested white
      tailed deer.

PMID- 22644382
TI  - Biofilm establishment and heavy metal removal capacity of an indigenous mining
      algal-microbial consortium in a photo-rotating biological contactor.
AB  - An indigenous mining algal-microbial consortium was immobilised within a
      laboratory-scale photo-rotating biological contactor (PRBC) that was used to
      investigate the potential for heavy metal removal from acid mine drainage (AMD).
      The microbial consortium, dominated by Ulothrix sp., was collected from the AMD
      at the Sar Cheshmeh copper mine in Iran. This paper discusses the parameters
      required to establish an algal-microbial biofilm used for heavy metal removal,
      including nutrient requirements and rotational speed. The PRBC was tested using
      synthesised AMD with the multi-ion and acidic composition of wastewater
      (containing 18 elements, and with a pH of 3.5 +/- 0.5), from which the microbial
      consortium was collected. The biofilm was successfully developed on the PRBC's
      disc consortium over 60 days of batch-mode operation. The PRBC was then run
      continuously with a 24 h hydraulic residence time (HRT) over a ten-week period.
      Water analysis, performed on a weekly basis, demonstrated the ability of the
      algal-microbial biofilm to remove 20-50 % of the various metals in the order Cu >
      Ni > Mn > Zn > Sb > Se > Co > Al. These results clearly indicate the significant
      potential for indigenous AMD microorganisms to be exploited within a PRBC for AMD
      treatment.

PMID- 22644383
TI  - Horizontal gene transfer and gene conversion drive evolution of modular
      polyketide synthases.
AB  - Soil bacteria live in a very competitive environment and produce many secondary
      metabolites; there appears to be strong selective pressure for evolution of new
      compounds. Secondary metabolites are the most important source of chemical
      structures for the pharmaceutical industry and an understanding of the
      evolutionary process should help in finding novel chemical entities. Modular
      polyketide synthases are a particularly interesting case for evolutionary
      studies, because much of the chemical structure can be predicted from DNA
      sequence. Previous evolutionary studies have concentrated on individual modules
      or domains and were not able to study the evolution of orthologues. This study
      overcame this problem by considering complete clusters as "organisms", so that
      orthologous modules and domains could be identified and used to characterise
      evolutionary pathways. Seventeen modular polyketide synthase clusters were
      identified that fell into six classes. Gene conversion within clusters was very
      common (affecting about 15 % of domains) and was detected by discordance in
      phylogenetic trees. An evolutionary model is proposed in which a single cross
      over between two different clusters (i.e. horizontal gene transfer) would
      generate a cluster of very different architecture with radically different
      chemical products; subsequent gene conversion and deletions would explore
      chemical variants. Two probable examples of such recombination were found. This
      model suggests strategies for detecting horizontal gene transfer in cluster
      evolution.

PMID- 22644384
TI  - Multi-compartment heart segmentation in CT angiography using a spatially varying
      gaussian classifier.
AB  - OBJECTIVE: A fully automated and efficient method for segmenting ten major
      structures within the heart in Cardiac CT Angiography data for the purposes of
      display or cardiac functional analysis. MATERIALS AND METHODS: A spatially
      varying Gaussian classifier is a flexible model for segmentation, combining the
      advantages of atlas-based frameworks, with supervised intensity models. It is
      composed of an independent Gaussian classifier at each voxel and uses non-rigid
      registration for the initial spatial alignment. We show how this large model can
      be trained efficiently and present a novel smoothing technique based on
      normalised convolution to mitigate inherent overfitting issues. The 30 datasets
      used in this study are selected from a variety of different scanners in order to
      test the robustness and stability of the algorithm. The datasets were manually
      segmented by a trained clinician. RESULTS: The method was evaluated in a leave
      one-out fashion, and the results were compared to other state of the art methods
      in the field, with a mean surface-to-surface distance of between 0.61 and 2.12 mm
      for different compartments. CONCLUSION: The accuracy of this method is comparable
      to other state of the art methods in the field. Its benefits lie in its
      conceptual simplicity and its general applicability. Only one non-rigid
      registration is required, giving it a speed advantage over multi-atlas
      approaches. Further accuracy may be achievable through the incorporation of an
      explicit shape model.

PMID- 22644385
TI  - A study of porcine liver motion during respiration for improving targeting in
      image-guided needle placements.
AB  - PURPOSE: Liver motion due to respiration restricts targeting and needle placement
      accuracy during image-guided interventional procedures. Breath holds, imaging
      techniques, and navigation systems are used to improve targeting accuracy. Data
      of in-vivo liver behavior under respiration can enhance these approaches.
      METHODS: An experimental study was performed using the swine model to capture the
      dynamics of liver motion during respiration using needles tipped with
      electromagnetic sensors. The swine liver was segmented into four lobes (right
      lateral, right medial, left medial and left lateral), and two sensor-tipped
      needles were placed in each location to acquire representative displacement data.
      RESULTS: Maximum displacement was found to occur in the left medial and left
      lateral lobes, in the anterior-posterior direction. Significant lobe-dependent
      variation in motion behavior was recorded, but a variation within a lobe was
      minimal and independent of needle approach. Magnitude of displacement in all
      lobes was found to be monotonically correlated to breathing volume. Displacement
      of liver was found to be out of phase with breathing by approximately 2 Hz. The
      positioning of the animal was also found to influence direction and magnitude of
      liver displacement in different lobes. CONCLUSIONS: We have presented previously
      unavailable data and insight into the role of easily controllable parameters such
      as breathing volume, patient positioning, and lobe-specific heterogeneity in the
      displacement of liver due to respiration.

PMID- 22644386
TI  - Independent prognostic value of whole-body metabolic tumor burden from FDG-PET in
      non-small cell lung cancer.
AB  - PURPOSE: To determine whether whole-body metabolic tumor burden, measured as
      either metabolic tumor volume (MTVWB) or total lesion glycolysis (TLGWB), using
      FDG-PET/CT is an independent prognostic marker in non-small cell lung cancer
      (NSCLC). METHODS: 328 patients with histologically proven NSCLC were identified
      for this retrospective analysis. This study was approved by our Institutional
      Review Board. All patients underwent baseline (18)F-FDG-PET/CT scan imaging
      before therapy. The MTVWB, TLGWB, maximum standardized uptake value (SUVmaxWB)
      and mean standardized uptake value (SUVmeanWB) of tumors throughout the whole
      body were measured from FDG-PET images with semi-automated 3D contouring
      software. RESULTS: In univariate analysis, there was a statistically significant
      association of overall survival (OS) with the MTVWB (hazard ratio (HR) = 1.62, p
      < 0.001), TLGWB (HR = 1.47, p < 0.001). The patients with a MTVWB <= median of
      65.7 ml and TLGWB <= median of 205.11 SUVmean * ml had a median OS of 41.1 and
      35.4 months compared with 9.5 and 9.7 months for those with a MTVWB > 65.7 ml and
      TLGWB > 205.11 SUVmean * ml, respectively. From a series of multivariate Cox
      regression models, the MTVWB and TLGWB were significantly better than SUVmaxWB
      and SUVmeanWB at prognostication and significantly associated with patients' OS
      with HRs of 1.50 (p < 0.001) and 1.42 (p < 0.001), respectively, after adjustment
      for patient's age, gender and treatment intent as well as the tumor SUVmaxWB,
      histology and stage. CONCLUSIONS: MTVWB and TLGWB as metabolic tumor burden
      measurements in (18)F-FDG-PET/CT are independent prognostic markers and are
      significantly better than SUVmaxWB and SUVmeanWB at prognostication.

PMID- 22644387
TI  - Basic biology and mechanisms of neural ciliogenesis and the B9 family.
AB  - Although the discovery of cilia is one of the earliest in cell biology, the past
      two decades have witnessed an explosion of new insight into these enigmatic
      organelles. While long believed to be vestigial, cilia have recently moved into
      the spotlight as key players in multiple cellular processes, including brain
      development and homeostasis. This review focuses on the rapidly expanding basic
      biology of neural cilia, with special emphasis on the newly emerging B9 family of
      proteins. In particular, recent findings have identified a critical role for the
      B9 complex in a network of protein interactions that take place at the ciliary
      transition zone (TZ). We describe the essential role of these protein complexes
      in signaling cascades that require primary (nonmotile) cilia, including the sonic
      hedgehog pathway. Loss or dysfunction of ciliary trafficking and TZ function are
      linked to a number of neurologic diseases, which we propose to classify as neural
      ciliopathies. When taken together, the studies reviewed herein point to critical
      roles played by neural cilia, both in normal physiology and in disease.

PMID- 22644388
TI  - Molecular dynamics simulations of lipid membrane electroporation.
AB  - The permeability of cell membranes can be transiently increased following the
      application of external electric fields. Theoretical approaches such as molecular
      modeling provide a significant insight into the processes affecting, at the
      molecular level, the integrity of lipid cell membranes when these are subject to
      voltage gradients under similar conditions as those used in experiments. This
      article reports on the progress made so far using such simulations to model
      membrane-lipid bilayer-electroporation. We first describe the methods devised to
      perform in silico experiments of membranes subject to nanosecond, megavolt-per
      meter pulsed electric fields and of membranes subject to charge imbalance,
      mimicking therefore the application of low-voltage, long-duration pulses. We show
      then that, at the molecular level, the two types of pulses produce similar
      effects: provided the TM voltage these pulses create are higher than a certain
      threshold, hydrophilic pores stabilized by the membrane lipid headgroups form
      within the nanosecond time scale across the lipid core. Similarly, when the
      pulses are switched off, the pores collapse (close) within similar time scales.
      It is shown that for similar TM voltages applied, both methods induce similar
      electric field distributions within the membrane core. The cascade of events
      following the application of the pulses, and taking place at the membrane, is a
      direct consequence of such an electric field distribution.

PMID- 22644389
TI  - In vivo molecular imaging and histological analysis of changes induced by
      electric pulses used for plasmid DNA electrotransfer to the skin: a study in a
      dorsal window chamber in mice.
AB  - Electropermeabilization/electroporation (EP) is a physical method that by
      application of electric pulses to cells increases cell membrane permeability and
      enables the introduction of molecules into the cells. One of the uses of EP in
      vivo is plasmid DNA electrotransfer to the skin for DNA vaccination. EP of
      tissues induces reduction of blood flow and, in combination with plasmid DNA,
      induction of an immune response. One of the EP protocols for plasmid DNA
      electrotransfer to the skin is a combination of high-voltage (HV) and low-voltage
      (LV) pulses. However, the effects of this pulse combination on skin-vessel blood
      flow are not known. Therefore, using intravital microscopy in a dorsal window
      chamber in mice and fluorescently labeled dextrans, the effects of one HV and
      eight LV pulses on skin vasculature were investigated. In addition, a detailed
      histological analysis was performed. Image analysis of fluorescence intensity
      changes demonstrated that EP induces a transient constriction and increased
      permeability of blood vessels as well as a "vascular lock." Histological analysis
      revealed rounding up of endothelial cells and stacking up of erythrocytes at 1 h
      after EP. In addition, extravasation of erythrocytes and leukocyte infiltration
      accompanied by edema were determined up to 24 h after EP. In conclusion, our
      results show that blood flow modifying effects of EP in skin contribute to the
      infiltration of immune cells in the exposed area. When combined with plasmid DNA
      for vaccination, this could enable the initial and prolonged contact of immune
      cells with encoded therapeutic proteins.

PMID- 22644390
TI  - Isolation of chromatin DNA tightly bound to the nuclear envelope of HeLa cells.
AB  - Recent discovery of the role of nuclear pores in transcription, predicted by our
      early DNA-membrane complex (DMC) model, makes membrane-bound DNA (MBD) isolation
      from the cell nucleus and analysis of the MBD actual. The method of MBD isolation
      proposed by us retains DMC integrity during isolation. We used HeLa cells for DMC
      extraction. Changing the ionic composition of the isolation medium and replacing
      DNase I, used commonly for chromatin destruction, with a set of restriction
      enzymes allowed us to isolate the MBD. Treatment of a nuclear membrane with
      proteinase K and ultrasound has been used to increase the yield of MBD. Electron
      microscopic analysis of the purified fraction of isolated DMC supports our
      previous model of nuclear envelope lipid-chromatin interaction in the nuclear
      pore assembly.

PMID- 22644392
TI  - Structural and functional dissection of aminocoumarin antibiotic biosynthesis: a
      review.
AB  - Aminocoumarin antibiotics are natural products of soil-dwelling bacteria called
      Streptomycetes. They are potent inhibitors of DNA gyrase, an essential bacterial
      enzyme and validated drug target, and thus have attracted considerable interest
      as potential templates for drug development. To date, aminocoumarins have not
      seen widespread clinical application on account of their poor pharmacological
      properties. Through studying the structures and mechanisms of enzymes from their
      biosynthetic pathways we will be better informed to redesign these compounds
      through rational pathway engineering. Novobiocin, the simplest compound, requires
      at least seventeen gene products to convert primary metabolites into the mature
      antibiotic. We have solved the crystal structures of four diverse biosynthetic
      enzymes from the novobiocin pathway, and used these as three-dimensional
      frameworks for the interpretation of functional and mechanistic data, and to
      speculate about how they might have evolved. The structure determinations have
      ranged from the routine to the challenging, necessitating a variety of different
      approaches.

PMID- 22644393
TI  - TP Atlas: integration and dissemination of advances in Targeted Proteins Research
      Program (TPRP)-structural biology project phase II in Japan.
AB  - The Targeted Proteins Research Program (TPRP) promoted by the Ministry of
      Education, Culture, Sports, Science and Technology (MEXT) of Japan is the phase
      II of structural biology project (2007-2011) following the Protein 3000 Project
      (2002-2006) in Japan. While the phase I Protein 3000 Project put partial emphasis
      on the construction and maintenance of pipelines for structural analyses, the
      TPRP is dedicated to revealing the structures and functions of the targeted
      proteins that have great importance in both basic research and industrial
      applications. To pursue this objective, 35 Targeted Proteins (TP) Projects
      selected in the three areas of fundamental biology, medicine and pharmacology,
      and food and environment are tightly collaborated with 10 Advanced Technology
      (AT) Projects in the four fields of protein production, structural analyses,
      chemical library and screening, and information platform. Here, the outlines and
      achievements of the 35 TP Projects are summarized in the system named TP Atlas.
      Progress in the diversified areas is described in the modules of Graphical
      Summary, General Summary, Tabular Summary, and Structure Gallery of the TP Atlas
      in the standard and unified format. Advances in TP Projects owing to novel
      technologies stemmed from AT Projects and collaborative research among TP
      Projects are illustrated as a hallmark of the Program. The TP Atlas can be
      accessed at http://net.genes.nig.ac.jp/tpatlas/index_e.html .

PMID- 22644394
TI  - Genetic host-tree effects on the ectomycorrhizal community and root
      characteristics of Norway spruce.
AB  - A greenhouse experiment was used to study the effects of host genotype on short
      root formation and ectomycorrhizal (ECM) fungal community structure in Norway
      spruce (Picea abies (L.) Karst.). Rooted cuttings representing 55 clones were
      inoculated with a mix of vegetative hyphae of five ECM fungal species (Laccaria
      sp., Amphinema byssoides, Piloderma sp., Cadophora finlandia, Paxillus
      involutus). After one growing season, the ECM fungal community structure was
      determined by amplifying the fungal internal transcribed spacer (ITS) of
      ribosomal DNA directly from ECM root tips. Restriction profiles of obtained
      amplicons were then compared to those of the inoculated strains. Spruce clones
      differed in their ECM fungal community composition; we found a statistically
      significant clone-specific effect on ECM fungal diversity and dominating fungal
      species. Nevertheless, the broad sense heritabilities of the levels of Laccaria
      sp., Piloderma sp. and A. byssoides colonisations as well as the ECM fungal
      community structure were low (H(2) = 0.04-0.11), owing to the high within-clone
      variation. As nitrogen concentration of needles correlated negatively with ECM
      fungal richness, our results imply that in the experimental conditions nutrient
      acquisition of young trees may benefit from colonisation with only one or two ECM
      fungal species. The heritability of short root density was moderate (H(2) = 0.41)
      and highest among all the measured shoot and root growth characteristics of
      Norway spruce cuttings. We suggest that the genetic component determining root
      growth and short root formation is significant for the performance of young trees
      in natural environments as these traits drive the formation of the below-ground
      symbiotic interactions.

PMID- 22644403
TI  - Left ventricular pseudoaneurysm following aortic valve prosthesis endocarditis.
AB  - A 63-year-old man underwent aortic valve replacement and an early reoperation for
      recurrent endocarditis. Sixteen months later he presented with persistent fever
      and a 64-slice computed tomography (CT) scan revealed a subannular left
      ventricular pseudoaneurysm. He underwent successful left ventricular outflow
      tract reconstruction and aortic valve prosthesis, partial root and ascending
      aorta replacement.

PMID- 22644404
TI  - Clinical presentation and long-term follow-up of perimyocarditis.
AB  - BACKGROUND: The natural history of perimyocarditis (PMY) is not yet completely
      known. We aimed to analyse the clinical laboratory data of PMY at diagnosis and
      during follow-up, in order to assess the natural history and prognostic
      stratification of the disease (including different aetiology). METHODS: We
      enrolled 62 consecutive patients (men 79%, aged 38 +/- 18 years) with PMY (84%
      idiopathic, 8% autoimmune, 8% infective) from August 2002 to July 2010. The
      diagnosis has been made according to clinical and laboratory data (significant
      increase of troponin I in all patients). After at least 1 year (mean follow-up:
      1635 +/- 298 days), 59 patients (95%) had available data. RESULTS: Chest pain was
      present in 59 patients (95%), flu-like syndrome in 36 (58%) and pericardial rubs
      in 15 (24%). None of the patients showed heart failure at presentation. At
      admission, eight patients (13%) presented mild-moderate left ventricular systolic
      dysfunction, 13 (22%) showed wall motion abnormalities, and 10 (17%) showed mild
      pericardial effusion. At 1 year no patients died, developed heart failure or
      showed abnormal echocardiogram. NSAIDs were the first choice therapy in 61 (98%)
      patients with clinical resolution in 58 (95%) of them. Seven patients (12%)
      experienced intermittent recurrences without development of constrictive
      pericarditis or heart failure. CONCLUSION: This study underlines the benign mid-
      to long-term outcome of PMY regardless of clinical laboratory characteristics at
      presentation, different aetiology and possibility of relapses; minimizing the
      role of endomyocardial biopsy in these specific patients.

PMID- 22644405
TI  - Where should transcatheter aortic valve implantation go beyond 2012?
AB  - Although surgical aortic valve replacement (sAVR) remains the gold standard
      treatment for severe, symptomatic aortic stenosis in a low-risk population, the
      role of transcatheter aortic valve implantation (TAVI) has increased
      significantly in the past decade and has entered the 'clinical mainstream' for
      the treatment of high-risk, inoperable patients. The transcatheter technique has
      evolved and improved immeasurably since its introduction some years ago. Not only
      is valve design evolving, but access site, size/technology of delivery systems
      and procedural technique are also undergoing continuous refinement. New devices
      are now available to prevent complications such as cerebral embolization, and
      occlusion balloons and covered stents are used to manage vascular complications
      more expertly. Early experiences are being gained in the treatment of failing
      bioprostheses - so-called 'valve-in-valve' therapy, even in the mitral position.
      In this article, we discuss the new transcatheter alternatives to open heart
      valve surgery and review the most recent clinical evidence and the currently
      available and emerging technology in transcatheter treatment.

PMID- 22644406
TI  - Rationale for cardiopulmonary exercise test in the assessment of surgical risk.
AB  - Although in the past years a reduced mortality in peri-operative care has been
      observed, cardiovascular mortality and morbidity still is a major burden in
      patients undergoing noncardiac surgery and its evaluation is still a difficult
      task. An accurate risk stratification can improve quality of peri-operative care
      and may improve survival, while reducing healthcare costs. In clinical practice,
      we make our assessment of a patient's cardiac status based on history,
      examination and investigations, together with risks related to the surgical
      procedure, to generate an 'individualized cardiac risk assessment'. At the
      present, risk stratification with clinical risk score and cardiac testing have
      been shown to be suboptimal in identifying high-risk patients. Surgery, like
      exercise, increases oxygen consumption. Indeed, one of the key elements in
      determining risk assessment is exercise intolerance, but future research in this
      field is needed to clarify this statement. Cardiopulmonary exercise testing
      (CPET) provides a global assessment of functional capacity involving and
      integrating the physiological measurement during incremental exercise. The
      pattern of CPET's variables identifies the abnormal exercise capacity, often
      providing an objective evaluation of cause and, moreover, predicting outcomes in
      both apparently healthy and chronic disease populations. An anaerobic threshold
      VO2 above 11 ml/kg per min seems to identify individuals with a very low surgical
      risk even if undergoing major surgery. This review is focused on tools of risk
      assessment in patients undergoing noncardiac surgery and on the physiological
      basis for CPET in detecting patients 'at risk'.

PMID- 22644407
TI  - Work burden with remote monitoring of implantable cardioverter defibrillator:  is
      it time for reimbursement policies?
AB  - AIMS: The efficacy and accuracy, as well as patients' satisfaction, of device
      remote monitoring are well demonstrated. However, the workload of remote
      monitoring management has not been estimated and reimbursement schemes are
      currently unavailable in most European countries. This study evaluates the
      workload associated with remote monitoring systems. METHODS: A total of 154
      consecutive implantable cardioverter defibrillator patients (age 66+/-12 years;
      86.5% men) with a remote monitoring system were enrolled. Data on the clinician's
      workload required for the management of the patients were analyzed. RESULTS: A
      total of 1744 transmissions were received during a mean follow-up of 15.3+/-12.4
      months. Median number of transmissions per patient was 11.3. There were 993 event
      free transmissions, whereas 638 transmissions regarded one or more events (113
      missed transmissions, 141 atrial events, 132 ventricular episodes, 299 heart
      failure-related transmissions, 14 transmissions regarding lead malfunction and
      164 transmissions related to other events). In 402 cases telephonic contact was
      necessary, whereas in 68 cases an in-clinic visit was necessary and in 23 of them
      an in-clinic visit was prompted by the manufacturer due to technical issues of
      the transmitter. During follow-up, 316 work hours were required to manage the
      enrolled patients. Each month, a total of 14.9 h were spent on the remote
      monitoring of 154 patients (9.7 h for 100 patients monthly) with approximately
      1.1+/-0.15 h per year for each patient. CONCLUSION: The clinician's work burden
      is high in patients with remote monitoring. In order to expand remote monitoring
      in all patients, reimbursement policies should be considered.

PMID- 22644408
TI  - Cancer incidence among Swedish pulp and paper mill workers: a cohort study of
      sulphate and sulphite mills.
AB  - PURPOSE: Associations between various malignancies and work in the pulp and paper
      industry have been reported but mostly in analyses of mortality rather than
      incidence. We aimed to study cancer incidence by main mill pulping process,
      department and gender in a Swedish cohort of pulp and paper mill workers.
      METHODS: The cohort (18,113 males and 2,292 females, enrolled from 1939 to 1999
      with >1 year of employment) was followed up for cancer incidence from 1958 to
      2001. Information on the workers' department and employment was obtained from the
      mills' personnel files, and standardized incidence ratios (SIRs) were calculated
      using the Swedish population as reference. RESULTS: Overall cancer incidence, in
      total 2,488 cases, was not increased by work in any department. However, risks of
      pleural mesothelioma were increased among males employed in sulphate pulping
      (SIR, 8.38; 95 % CI, 3.37-17) and maintenance (SIR, 6.35; 95 % CI, 3.47-11), with
      no corresponding increase of lung cancer. Testicular cancer risks were increased
      among males employed in sulphate pulping (SIR, 4.14; 95 % CI, 1.99-7.61) and
      sulphite pulping (SIR, 2.59; 95 % CI, 0.95-5.64). Female paper production workers
      showed increased risk of skin tumours other than malignant melanoma (SIR, 2.92;
      95 % CI, 1.18-6.02). CONCLUSIONS: Incidence of pleural mesothelioma was increased
      in the cohort, showing that asbestos exposure still has severe health
      consequences, and highlighting the exigency of strict asbestos regulations and
      elimination. Testicular cancer was increased among pulping department workers.
      Shift work and endocrine disruptors could be of interest in this context.

PMID- 22644409
TI  - Symptoms of heat illness in surface mine workers.
AB  - OBJECTIVE: To assess the symptoms of heat illness experienced by surface mine
      workers. METHODS: Ninety-one surface mine workers across three mine sites in
      northern Australia completed a heat stress questionnaire evaluating their
      symptoms for heat illness. A cohort of 56 underground mine workers also
      participated for comparative purposes. Participants were allocated into
      asymptomatic, minor or moderate heat illness categories depending on the number
      of symptoms they reported. Participants also reported the frequency of symptom
      experience, as well as their hydration status (average urine colour). RESULTS:
      Heat illness symptoms were experienced by 87 and 79 % of surface and underground
      mine workers, respectively (p = 0.189), with 81-82 % of the symptoms reported
      being experienced by miners on more than one occasion. The majority (56 %) of
      surface workers were classified as experiencing minor heat illness symptoms, with
      a further 31 % classed as moderate; 13 % were asymptomatic. A similar
      distribution of heat illness classification was observed among underground miners
      (p = 0.420). Only 29 % of surface miners were considered well hydrated, with 61 %
      minimally dehydrated and 10 % significantly dehydrated, proportions that were
      similar among underground miners (p = 0.186). Heat illness category was
      significantly related to hydration status (p = 0.039) among surface mine workers,
      but only a trend was observed when data from surface and underground miners was
      pooled (p = 0.073). Compared to asymptomatic surface mine workers, the relative
      risk of experiencing minor and moderate symptoms of heat illness was 1.5 and 1.6,
      respectively, when minimally dehydrated. CONCLUSIONS: These findings show that
      surface mine workers routinely experience symptoms of heat illness and highlight
      that control measures are required to prevent symptoms progressing to medical
      cases of heat exhaustion or heat stroke.

PMID- 22644411
TI  - Detection of ATP by "in line" 31P magnetic resonance spectroscopy during
      oxygenated hypothermic pulsatile perfusion of pigs' kidneys.
AB  - OBJECT: To demonstrate that adenosine triphosphate (ATP), which provides a
      valuable biomarker for kidney viability in the context of donation after cardiac
      death (DCD) transplantation, can be detected by means of (31)P magnetic resonance
      spectroscopy (MRS) if kidneys are perfused with oxygenated hypothermic pulsatile
      perfusion (O(2)+HPP). MATERIALS AND METHODS: Porcine kidney perfusion was carried
      out using a home made, MR-compatible HPP-machine. Consequently, kidney perfusion
      could be performed continuously during magnetic resonance imaging and magnetic
      resonance spectroscopy recording. (31)P MR spectroscopy consisted of 3
      dimensional chemical shift imaging (CSI), which allowed for the detection of ATP
      level in line. (31)P CSI was performed at 3 tesla in 44 min with a nominal voxel
      size of 6.1 cc. RESULTS: (31)P CSI enabled the detection of renal ATP when pO(2)
      was equal to 100 kPa. With pO(2) of 20 kPa, only phosphomonoester, inorganic
      phosphate and nicotinamide adenine dinucleotide could be found. Semi-quantitative
      analysis showed that ATP level was 1.3 mM in normal kidney perfused with pO(2) of
      100 kPa. CONCLUSIONS: This combined technology may constitute a new advance in
      DCD organ diagnostics prior to transplantation, as it allows direct assessment of
      ATP concentration, which provides a reliable indicator for organ bioenergetics
      and viability. In this study, kidneys presenting no warm ischemia were tested in
      order to establish values in normal organs. The test could be easily integrated
      into the clinical environment and would not generate any additional delay into
      the transplantation clinical workflow.

PMID- 22644412
TI  - Hepatic arterial embolization for unresectable hepatocellular carcinomas: do
      technical factors affect prognosis?
AB  - PURPOSE: To evaluate retrospectively whether technical factors of hepatic
      arterial embolization affect the prognosis of patients with hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: Inclusion criteria of this study were the
      following: (1) patients received embolization as the initial treatment during
      2003-2004, (2) Child A or B liver profile, (3) five or fewer HCCs with maximum
      diameter of 7 cm or smaller, and (4) no extrahepatic metastasis. Patient data
      were gathered from 43 centers. Prognostic factors were evaluated using univariate
      and multivariate analyses. RESULTS: Eight hundred fifteen patients were enrolled.
      The 1-, 3-, 5-, and 7-year overall survival rates were 92.0 % (95 % CI 90.1
      93.9), 62.9 % (95 % CI 59.3-66.6), 39.0 % (95 % CI 35.1-43.0), and 26.7 % (95 %
      CI 22.6-30.8) in all patients. Univariate analysis showed a Child-Pugh class-A,
      alpha-fetoprotein level lower than 100 ng/ml, tumor size of 3 cm or smaller,
      tumor number of 3 or fewer, one-lobe tumor distribution, nodular tumor type,
      within the Milan criteria, stage I or II, no portal venous invasion, use of
      iodized oil, and selective embolization were significantly better prognostic
      factors. In the multivariate Cox model, the benefit to survival of selective
      embolization remained significant (hazard ratio 0.68; 95 % CI 0.48-0.97; p =
      0.033). CONCLUSION: Selective embolization contributes to survival in patients
      with HCCs.

PMID- 22644413
TI  - Giant cardiac fibroma: an unusual cause of failure to thrive.
AB  - Cardiac fibromas are extremely rare in the general pediatric population and may
      present with a wide spectrum of clinical signs, including life-threatening
      arrhythmias and sudden death. We report a 14-month-old boy who presented with
      failure to thrive as the only symptom. Echocardiography showed a large cardiac
      fibroma in the right ventricle. Cardiac magnetic resonance imaging confirmed the
      diagnosis. After complete surgical tumor resection, the boy showed normal catch
      up growth. This case underlines the diversity of clinical features of cardiac
      tumors, which implies that they should be considered early in the differential
      diagnosis of infants with failure to thrive.

PMID- 22644415
TI  - Iatrogenic aortopulmonary fistula occurring after pulmonary artery balloon
      angioplasty: a word of caution.
AB  - We describe the natural history of an adolescent patient who developed an
      aortopulmonary fistula (APF) after transcatheter stent placement for left
      pulmonary artery stenosis after neonatal repair of d-transposition of the great
      arteries. Due to its rarity, the APF was not initially diagnosed and treated
      until 4 months later. The APF was occluded with a covered stent. Because this is
      not an isolated report in the literature, we believe it should be considered as a
      potential complication in all patients after balloon dilation of stenotic
      pulmonary artery branches after arterial switch surgery.

PMID- 22644416
TI  - Catheter interventions in congenital heart disease without regular
      catheterization laboratory equipment: the chain of hope experience in Rwanda.
AB  - This report describes the feasibility and safety of cardiac catheterization in a
      developing country without access to a regular cardiac catheterization
      laboratory. The equipment used for imaging consisted of a monoplane conventional
      C-arm X-ray system and a portable ultrasound machine using the usual guidewires
      and catheters for cardiovascular access. In this study, 30 patients, including 17
      children younger than 2 years and 2 adults, underwent catheterization of the
      following cardiac anomalies: patent ductus arteriosus (20 patients) and pulmonary
      valve stenosis (9 patients, including 2 patients with critical stenosis and 3
      patients with a secundum atrial septal defect). Except for two cases requiring
      surgery, the patients were treated successfully without complications. They all
      were discharged from hospital, usually the day after cardiac catheterization, and
      showed significant clinical improvement in the follow-up evaluation. Cardiac
      catheterization can be performed safely and very effectively in a country with
      limited resources. If patients are well selected, this mode of treatment is
      possible without the support of a sophisticated catheterization laboratory.

PMID- 22644414
TI  - Outcome of extremely preterm infants (<1,000 g) with congenital heart defects
      from the National Institute of Child Health and Human Development Neonatal
      Research Network.
AB  - Little is known about the outcomes of extremely low birth weight (ELBW) preterm
      infants with congenital heart defects (CHDs). The aim of this study was to assess
      the mortality, morbidity, and early childhood outcomes of ELBW infants with
      isolated CHD compared with infants with no congenital defects. Participants were
      401-1,000 g infants cared for at National Institute of Child Health and Human
      Development Neonatal Research Network centers between January 1, 1998, and
      December 31, 2005. Neonatal morbidities and 18-22 months' corrected age outcomes
      were assessed. Neurodevelopmental impairment (NDI) was defined as moderate to
      severe cerebral palsy, Bayley II mental or psychomotor developmental index <70,
      bilateral blindness, or hearing impairment requiring aids. Poisson regression
      models were used to estimate relative risks for outcomes while adjusting for
      gestational age, small-for-gestational-age status, and other variables. Of 14,457
      ELBW infants, 110 (0.8 %) had isolated CHD, and 13,887 (96 %) had no major birth
      defect. The most common CHD were septal defects, tetralogy of Fallot, pulmonary
      valve stenosis, and coarctation of the aorta. Infants with CHD experienced
      increased mortality (48 % compared with 35 % for infants with no birth defect)
      and poorer growth. Surprisingly, the adjusted risks of other short-term neonatal
      morbidities associated with prematurity were not significantly different. Fifty
      seven (52 %) infants with CHD survived to 18-22 months' corrected age, and 49 (86
      %) infants completed follow-up. A higher proportion of surviving infants with CHD
      were impaired compared with those without birth defects (57 vs. 38 %, p = 0.004).
      Risk of death or NDI was greater for ELBW infants with CHD, although 20 % of
      infants survived without NDI.

PMID- 22644417
TI  - Dual right coronary arteries in transposition of great arteries.

PMID- 22644418
TI  - Heterotaxy syndrome: is a prophylactic Ladd procedure necessary in asymptomatic
      patients?
AB  - Heterotaxy syndrome (HS) is a complex disorder involving thoracic and abdominal
      asymmetries. Congenital heart disease is often accompanied by an intestinal
      rotation abnormality (IRA) that may predispose to bowel ischemia and infarction.
      There is controversy in the literature whether asymptomatic infants with HS must
      be screened for IRA and, if present, whether a prophylactic Ladd procedure should
      be performed. We performed a retrospective chart review of all patients who
      underwent a Ladd procedure from January 2007 to December 2010 at Stollery
      Children's Hospital, Edmonton, Canada. Twenty-nine patients underwent a Ladd
      procedure, 22 without HS but with symptomatic malrotation and 7 with HS and
      asymptomatic malrotation. Asymptomatic HS patients had a complication rate of 57
      % after a prophylactic Ladd procedure compared with a complication rate of 9 % in
      the symptomatic non-HS population. The management of asymptomatic IRA in patients
      with HS remains controversial. We suggest that HS patients be screened for IRA
      and that asymptomatic patients be managed conservatively.

PMID- 22644419
TI  - Large right ventricular fibroma in a 6-month-old infant.
AB  - This report describes the case of a 6-month-old girl with a large cardiac fibroma
      in the right ventricle. Ventricular tachycardia associated with the fibroma was
      successfully treated with amiodarone. At the age of 3 years, surgical resection
      was indicated because of right ventricular outflow tract obstruction caused by
      progression of the tumor. The fibroma was successfully resected, and further
      follow-up evaluation was uneventful.

PMID- 22644421
TI  - Edge loading has a paradoxical effect on wear in metal-on-polyethylene total hip
      arthroplasties.
AB  - BACKGROUND: Edge wear is an adverse factor that can negatively impact certain
      THAs. In some metal-on-metal THAs, it can lead to adverse tissue reactions
      including aseptic lymphocytic vasculitis-associated lesions and even to
      pseudotumor formation. In some ceramic-on-ceramic THAs, it can lead to squeaking
      and/or stripe wear. Edge wear in metal-on-metal and ceramic-on-ceramic THAs can
      also be associated with accelerated wear across the articulation of these joints.
      QUESTIONS/PURPOSES: I asked: Does edge wear occur in metal-on-polyethylene (MOP)
      articulations? And if so, does it increase joint wear? METHODS: I examined the
      evidence in the literature for edge wear occurring in MOP THA and then assessed
      the evidence in the literature for data supporting the concept that edge wear in
      MOP hips could accelerate wear across the articulation over time. RESULTS:
      Extensive data in the literature confirm edge wear is common in MOP THA.
      Surprisingly, the evidence does not support that it accelerates wear across the
      articulation. In fact, substantial data support the concept that it does not.
      CONCLUSIONS: These observations suggest, in terms of edge wear accelerating
      overall wear, MOP articulation may have a privileged position compared to hard-on
      hard THA articulations.

PMID- 22644420
TI  - What do we know about what happens to myometrial function as women age?
AB  - Much has been written about the effects of aging on reproductive function,
      especially female fertility. Much less is known about how aging may affect the
      contractility of the smooth muscle within the uterus, the myometrium. The
      myometrium is active through a woman's entire life, not just during pregnancy.
      Here we will discuss briefly the contractile functions of the uterus and the
      changes it undergoes throughout the stages of a woman's life from menstruation
      and the menopause, before evaluating the evidence for any changes in myometrial
      contractility and responses as women age, with a particular focus on women of
      advanced maternal age. We present original contractility analysis for the widest
      data set for human myometrium so far examined, and determine inherent spontaneous
      activity as well as responses to depolarisation and stimulation with oxytocin.
      Our data show that in the non-pregnant state there is a significant decrease in
      contractility for both spontaneous and depolarised-induced contractions, with
      age. We suggest that muscle atrophy and down regulation of Ca channels may
      account for this. Interestingly in pregnant myometrium we found a wide range of
      contractile ability between women and little evidence for decreased spontaneous
      activity between the ages of 25-40. Oxytocin responses appear to be more affected
      by aging, a finding that is consistent with previously reported clinical
      findings, and may partly be the result of membrane lipids such as cholesterol,
      increasing as women age. The marked differences between the age-related decline
      of force beyond age 30 in non-pregnant uterus, and the lack of difference in the
      pregnant state over this period, shows that the uterus retains its ability to
      respond to gestational hormones. The growth of the pregnant uterus and increase
      in content of myofibrillar proteins, may abolish any previous age-related force
      deficit. This finding is consistent with what is apparent for postmenopausal
      women in their 50s and 60s; that with the appropriate hormonal stimulation the
      uterus can allow an embryo to implant, and then without further intervention,
      carry the foetus to term. It is tempting therefore to speculate that unlike other
      well documented declines in female reproductive functions with age, the
      myometrium remains able to function into a woman's 7th decade.

PMID- 22644422
TI  - Head material influences survival of a cemented total hip prosthesis in the
      Norwegian Arthroplasty Register.
AB  - BACKGROUND: High prosthesis survival is reported for total hip prostheses with
      metal and alumina heads, but direct comparisons of a single prosthesis design
      with one of two different head materials has seldom been studied. Prostheses with
      zirconia heads are less commonly used than metal and alumina heads, and the few
      reports suggest variable results with zirconia heads. QUESTIONS/PURPOSES: We
      therefore asked: (1) Would metal heads provide better survival of a cemented
      total hip arthroplasty (THA) than alumina heads? (2) Would metal heads provide
      better survival of a cemented THA than zirconia heads? METHODS: We searched in
      the Norwegian Arthroplasty Register for cemented primary THA cup/stem
      combinations that simultaneously had been used with different head materials. The
      only THA that fulfilled these inclusion criteria was the cemented Reflection All
      Poly/Spectron EF (cup/stem) that had during 2001 to 2006 been used both with
      alumina (n = 448) and cobalt-chromium (n = 5229) heads; that implant had also
      been used with zirconia (n = 275) and cobalt-chromium heads (n = 3195) during
      1997 to 2003, and we included patients with this THA from these two time
      intervals in the study. All cups were conventional polyethylene. We estimated
      prosthesis survival and relative revision risks adjusting for age, sex, and
      diagnosis. The followup in the two study materials was until December 2010.
      RESULTS: The survival at 8 years of the Spectron EF/Reflection THAs, inserted
      with alumina and cobalt-chromium heads during 2001 to 2006, was 92.3% and 94.0%,
      respectively. The Reflection/Spectron EF THA had inferior survival with zirconia
      heads compared with cobalt-chromium heads (relative risk, 1.7). At 12 years, the
      survival rate was 88.1% with cobalt-chromium heads and 74.8% with zirconia heads.
      CONCLUSIONS: Alumina femoral heads provided no advantage over cobalt-chromium
      heads on midterm prosthesis survival. THAs with zirconia heads had inferior
      survival. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 22644423
TI  - Peripheral triangular fibrocartilage complex tears cause ulnocarpal instability:
      a biomechanical pilot study.
AB  - BACKGROUND: Instability at the ulnocarpal joint has many causes, but the common
      thread among these causes is the presence of abnormalities in the triangular
      fibrocartilage complex (TFCC). However, the biomechanical consequences at the
      ulnocarpal joint after detachment of the TFCC from the ulnar styloid are not
      clearly defined. Better delineation of whether peripheral TFCC detachments cause
      ulnocarpal instability will help to design surgical treatments.
      QUESTIONS/PURPOSES: We asked whether detachment of the peripheral TFCC from the
      ulnar styloid causes ulnocarpal instability. METHODS: Using 20 fresh-frozen below
      elbow cadaver specimens, the distal ulna was cycled volarly and dorsally with the
      carpus held firmly. The load-displacement curve was analyzed to determine the
      resistance of the ulnocarpal joint against dorsal-volar displacement of the ulna
      (stiffness) and the amount of dorsal-volar excursion with minimal resistance
      before reaching firm end points dorsally and volarly. A standardized 3-mm
      transection of the attachment of the TFCC from the ulnar styloid was created with
      a scalpel using arthroscopic observation. Mechanical testing was repeated and
      paired Student's t-tests conducted. RESULTS: The mean stiffness of the ulnocarpal
      joint was decreased after detachment. The amount of dorsal-volar excursion was
      similar after detachment of the peripheral TFCC. CONCLUSIONS: There is decreased
      stiffness at the ulnocarpal joint after detachment of the peripheral TFCC, but
      there is no biomechanically detectable difference in dorsal-volar excursion.
      CLINICAL RELEVANCE: The findings of the current study can be used to develop and
      evaluate innovative surgical techniques, such as capsulorraphy or ligamentous
      reconstruction, that specifically address laxity at the ulnocarpal joint after
      peripheral TFCC detachment.

PMID- 22644424
TI  - High failure rate with the GAP II ring and impacted allograft bone in severe
      acetabular defects.
AB  - BACKGROUND: Reconstruction rings and bone allografts have been proposed to manage
      severe acetabular bone loss. However, a high early failure rate of the Graft
      Augmentation Prosthesis (GAP) II reinforcement ring (Stryker Orthopaedics,
      Mahwah, NJ, USA) has been reported in one small series. QUESTIONS/PURPOSES: We
      therefore determined (1) the survival of this device in combination with impacted
      morselized allograft bone in patients with severe defects and (2) the
      complication rate. METHODS: We retrospectively reviewed 24 patients (21 aseptic
      and three septic) with severe acetabular bone loss (10 hips with Type III defects
      and 14 with Type IV defects according to the American Academy of Orthopaedic
      Surgeons classification). We determined function and numbers of failures. The
      minimum followup was 24 months (mean, 34 months; range, 24-72 months). RESULTS:
      At latest followup, the reconstruction had failed in nine of the 24 patients: six
      with aseptic loosening, three with infection. The average postoperative Merle
      d'Aubigne-Postel score of the patients whose reconstructions had not failed was
      16.6 points; at latest followup, these patients had radiographic evidence of
      incorporation and consolidation of bone allografts. Seven of the nine patients
      whose reconstructions had failed underwent reoperation. Fatigue fracture of the
      ring at the plate-cup union occurred in five patients at an average of 45 months
      postoperatively. All patients with failed reconstructions who underwent
      reoperation were treated with Trabecular Metal(TM) (Zimmer Inc, Warsaw, IN, USA)
      cups and were functioning well at latest followup. CONCLUSIONS: We observed a
      high rate (37%) of early catastrophic failures of the GAP II reconstruction ring,
      particularly in patients with Type IV defects. Due to this high failure rate, we
      have abandoned its use. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the
      Instructions for Authors for a complete description of levels of evidence.

PMID- 22644425
TI  - 2011 Mid-America Orthopaedic Association Dallas B. Phemister Physician in
      Training Award: Can musculoskeletal tumors be diagnosed with ultrasound fusion
      guided biopsy?
AB  - BACKGROUND: Percutaneous biopsy for musculoskeletal tumors commonly relies on
      imaging adjuncts including ultrasound (US), CT, or MRI. These modalities however
      have disadvantages (US) or are cumbersome, not universally available, and costly
      (CT and MRI). US fusion is a novel technique that fuses previously obtained CT or
      MRI data with real-time US, which allows biopsies to be performed in an US suite.
      It has proven useful in various body systems but musculoskeletal applications
      remain scarce. Our goal is to evaluate the fusion technology and determine its
      ability to diagnose musculoskeletal tumors. QUESTIONS/PURPOSES: We determined
      whether biopsies performed via US fusion compared with CT guidance provide
      equivalent diagnostic yield and accuracy and allow quicker biopsy scheduling and
      procedure times. METHODS: Forty-seven patients were assigned to undergo either US
      fusion (with MR, n = 16 or CT, n = 15) or CT-guided biopsies (n = 16). We
      evaluated adequacy of the histologic specimen (diagnostic yield) and correlation
      with surgical pathology (diagnostic accuracy). We determined scheduling times and
      lengths of the biopsy. RESULTS: US fusion and CT-guided biopsy groups had
      comparable diagnostic yields (CT = 94%; US/MRI = 94%; US/CT = 93%) and accuracy
      (CT = 83%; US/MRI = 90%; US/CT = 100%). US fusion biopsies were faster to
      schedule and perform. All procedures were safe with minimal complications.
      CONCLUSIONS: US fusion provides a high diagnostic yield and accuracy comparable
      to CT-guided biopsy while performed in the convenience of an US suite. This may
      have resulted in the observed faster scheduling and biopsy times. LEVEL OF
      EVIDENCE: Level II, diagnostic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 22644426
TI  - Violence exposure mediates the relation between callous-unemotional traits and
      offending patterns in adolescents.
AB  - The link between callous-unemotional (CU) traits in youth and delinquent,
      aggressive and violent behavior is well-replicated in the literature. However,
      the mediating effects of violence exposure on this relationship are unclear. The
      current study addresses this important gap in the literature with a sample of 88
      detained, primarily ethnic minority adolescent boys (M age = 15.57; SD = 1.28).
      Results indicate that exposure to violence fully mediated the relationship
      between CU traits and violent delinquency, and this pattern of mediation was
      accounted for by exposure to witnessed violence, but not direct violent
      victimization. Secondly, exposure to violence, both direct and witnessed forms,
      also mediated the relationship between CU traits and drug delinquency. These
      findings suggest that (a) the well-established link between CU traits and
      violence may be attributed to high rates of witnessed violence among this
      subpopulation, and (b) specific types of violence exposure may be important for
      predicting the offending patterns of youth high on CU traits. Theoretical and
      practical implications are discussed.

PMID- 22644427
TI  - Perinatal factors, parenting behavior, and reactive aggression: does cortisol
      reactivity mediate this developmental risk process?
AB  - Little is known about the mechanisms of action that link perinatal risk and the
      development of aggressive behavior. The aim of this study was to examine whether
      perinatal risk and parenting interacted to specifically predict reactive
      aggression, as opposed to general aggressive behavior, and to examine cortisol
      reactivity as a mediator of this developmental risk process. In a community
      sample of 99 elementary school-aged children, prenatal risk was measured by a
      count of minor physical anomalies (MPAs), reactive aggression was measured by
      laboratory observations of aggression in response to provocation, and general
      aggression was measured by parent report. Cortisol reactivity was not found to
      mediate the association between MPAs and reactive aggression or general
      aggression. However, MPAs were found to interact with parenting behaviors to
      predict reactive aggression and general aggression, as well as cortisol
      reactivity. Specifically, as the deficits in parenting increased, MPAs became
      more strongly and positively associated with reactive aggressive and general
      aggressive outcomes. Similarly, in cases of poor parenting behaviors, MPAs were
      positively associated with higher cortisol reactivity. Implications for theory
      and prevention are discussed.

PMID- 22644428
TI  - What should be the research agenda for developmental behavioral pediatrics?
AB  - This commentary recognizes the great accomplishment and future potential of
      research in developmental and behavioral pediatrics. It cautions against
      endorsing a longterm strategy of choosing relevant research topics based solely
      on today's population trends, as these are likely to change over time. The
      commentary supports DBPNet's own research emphases on autism and attention
      deficit disorder based on their own interests and the specific goals supported by
      their funding mechanism.

PMID- 22644429
TI  - Guidewire localization with transesophageal echocardiography: do not forget the
      left side.

PMID- 22644430
TI  - Failure of both suction catheter passage and bronchoscopy to diagnose an
      obstructing tracheal mucus plug.

PMID- 22644431
TI  - Shelf life of rechargeable laryngoscope batteries without recharging.

PMID- 22644432
TI  - Simulations of X-ray absorption spectra: the effect of the solvent.
AB  - We perform quantum mechanics/molecular mechanics molecular dynamics simulations
      on the [Pt(2)(P(2)O(5)H(2))(4)](4-) (abbreviated PtPOP) complex; in water,
      dimethylformamide and ethanol. These are used to calculate the ground state X-ray
      absorption spectrum of the complex. The structural parameters from X-ray spectra
      are usually extracted using a fit of the experimental data. In such simulations
      the solvent is neglected meaning that any effect of the local environment will be
      compensated for by structural changes of the solute, leading to possible
      discrepancies in the extracted structural parameters. Our simulations show a
      significant solvent effect on the spectra, which has important implications for
      the structural analysis of molecules in solution.

PMID- 22644433
TI  - Comparative analysis of complications of different reconstructive techniques
      following anterior decompression for multilevel cervical spondylotic myelopathy.
AB  - PURPOSE: Anterior approach was extensively used in surgical treatment of
      multilevel cervical spondylotic myelopathy. Following anterior decompression,
      many different reconstructive techniques (multilevel ACDF, hybrid construct and
      long corpectomy) all had satisfied outcomes. However, there are few studies
      focusing on the comparison of these three reconstructed techniques. The aim of
      this retrospective study was to analyze the complications of these three
      different methods. METHODS: This study retrospectively reviewed the complications
      in 286 consecutive patients with multilevel CSM who underwent anterior cervical
      surgery from 2005 to 2010. This case series had 166 men and 120 women whose mean
      age at surgery was 53.8 years (range from 33 to 74 years). Radiographic
      evaluation was taken the day after surgery, and the flexion-extension X-rays were
      added 3, 12 and 24 months postoperatively to evaluate the fusion condition.
      Preoperative versus postoperative neurologic function and clinical outcome were
      evaluated using scoring systems such as the Japanese Orthopedic Association (JOA
      score), Neck Disability Index (NDI score) and 36-Item Short-Form Health Survey
      (SF-36 score). RESULTS: There were no significant differences in JOA scores, NDI
      scores and SF-36 scores of the pairwise comparison among the three groups. The
      complications in our series included graft migration, collapse or displacement,
      hoarseness, dysphagia, C5 palsy, cerebral fluid leakage and wound infection.
      Sixty-one patients developed complications after surgery and the rate of
      complication was 21.33 %. Patients in the long corpectomy group had the highest
      rate of complications; the other two groups had a much lower rate of
      complications by the latest follow-up. The patients in the multilevel ACDF group
      had the highest fusion rate by the last follow-up. Patients who had C2-3 and C3-4
      segments involved had a higher rate of postoperative hoarseness and dysphagia.
      CONCLUSIONS: Most of the complications of the three reconstructive techniques
      subsided gradually after conservative treatment; none of them needed revision
      surgery. The multilevel ACDF approach has the lowest rate of non-union, but a
      slightly higher morbidity of the laryngeal nerve-related complication if proximal
      segments were involved. The long corpectomy approach should be selected prudently
      because of the high rate of complication.

PMID- 22644435
TI  - Anterior instrumentation (dual screws single rod system) for the surgical
      treatment of idiopathic scoliosis in the lumbar area: a prospective study on 33
      adolescents and young adults, based on a new system of classification.
AB  - OBJECTIVES/PURPOSE: The choice of anterior instrumentation in the treatment of
      lumbar scoliosis in adolescents and young adults is not a new topic for the
      authors. The first results achieved using the Dwyer surgical modality were
      reported by one of the authors followed by the results achieved using Zielke
      (VDS) instrumentation. Today, new techniques and new instrumentations have been
      developed that challenge the instrumentation choices. Here we describe how the
      new system of classification of scoliotic curves we developed has been used as a
      basis for treating idiopathic scoliosis in lumbar area in adolescents and young
      adults using an anterior approach. MATERIALS: A prospective study was carried out
      between 1998 and 2010 at two hospital centers on 33 adolescents and young adult
      with idiopathic lumbar scoliosis involving curves of three kinds, on whom
      surgical treatment was performed using a single solid rod. Topography of curves:
      our system of classification includes curves corresponding to the following three
      type of scoliosis: Type K I: double thoracic and lumbar curves (lumbar
      predominant) scoliosis (17 cases) mean age 16 years all female patients. Mean
      Cobb angle of lumbar curve 41 degrees . Mean Cobb angle of thoracic curve 28
      degrees . The lumbar curve was left hand convex in 15 cases and right hand convex
      in 2 cases. Horizontal tilting of L4 mean value 22 degrees . C7 offset mean value
      3 cm. Type K IV A: unbalanced thoracolumbar scoliosis (13 cases) mean age 17
      years, ten female patients and three male patients. Mean Cobb angle of
      thoracolumbar curve 39 degrees . The thoracolumbar curve was left hand convex 4
      times and right hand convex 9 times. Horizontal tilting of L4 mean value 18
      degrees . C 7 offset mean value 2.5 cm. Type K VI A: real lumbar (three cases).
      Age: 17, 15 and 13 years; all female patients. Cobb angle of the lumbar curve 66
      degrees , 29 degrees  and 70 degrees  (all LH convex). Horizontal tilting of L4:
      40 degrees , 20 degrees  and 46 degrees . C 7 offset: 7 cm, 1 cm and 4 cm.
      METHODS: Surgical instrumentation: We used the EUROS AZUR anterior
      instrumentation for all the procedures. Cages have been used on five patients at
      the lower stages. Number of vertebrae instrumented: mean five vertebrae. The
      patients did not wear postoperative orthosis. Mean duration of procedure: 3 h 50
      min. Mean blood loss: 350 cm(3). RESULTS: Type K I scoliosis (17 cases): Mean
      follow-up: 6 years. Correction of the lumbar curve Cobb angle: the mean angle has
      been corrected from 41 degrees  to 21 degrees . Number of vertebrae instrumented:
      4:6 times and 5:11 times. Correction of the upper thoracic curve Cobb angle: mean
      angle corrected from 28 degrees  to 19 degrees . Correction of L4 horizontal
      tilting: mean residual was 7 degrees . Correction of C 7 offset: mean 0.7 cm.
      Type K IV A scoliosis (13 cases): mean follow-up: 4 years. Correction of the
      lumbar curve Cobb angle: the mean angle has been corrected from 39 degrees  to 16
      degrees . Mean number of instrumented vertebrae: 5 (4:4 times, 5:6 times and 6:3
      times.) Correction of L4 horizontal tilting: mean residual 5 degrees . Correction
      of C 7 offset: mean 0.7 cm. Type K VI A scoliosis (three cases): mean follow-up:
      7, 2 and 4 years; Correction of the lumbar curve Cobb angle: the angles have been
      corrected from 66 degrees  to 15 degrees , from 29 degrees  to 11 degrees  and
      from 70 degrees  to 28 degrees . Number of instrumented vertebrae: 5, 4 and 6.
      Correction of L4 horizontal tilting: residual tilting of 8 degrees , 7 degrees 
      and 17 degrees . Correction of C 7 offset: 1 cm, 0 cm and 1 cm. COMPLICATIONS:
      There has been no report early or late septic or vascular or neurological
      complications. Instrumentation failure: there were three cases of screw breakage,
      all occurred on the lowest implant. Revision surgery was undertaken in both
      cases, only the last plate needed to be replaced and the rod could be kept
      without any other modification of the construct. In both cases, fusion has been
      achieved without any loss of correction. The mean loss of correction of the main
      curve was 2.5 degrees  for the three series. CONCLUSIONS: Anterior
      instrumentation of lumbar idiopathic scoliosis gives highly satisfactory
      morphological and functional results, since the lumbar musculature is spared and
      the instrumentation placed at the apex of the curvature has selective effects.
      Despite our preference and that of other surgeons throughout the world for
      anterior instrumentation, we are still a minority in comparison with the users of
      posterior instrumentation. There are several reasons for this reticence,
      including surgeons' training and ideas about pedicular screw fixation, but the
      main reason has been the lack of a sufficiently exact system of classification.
      Previous comparative studies between the anterior and posterior approaches have
      been biased by the use of an excessively restrictive mode of classification
      (lumbar/thoracolumbar) of the curves. Real lumbar scoliosis, unbalanced
      thoracolumbar scoliosis and thoracic and lumbar double curve (lumbar predominant)
      scoliosis should be properly defined before being compared.

PMID- 22644437
TI  - The effects of upper limb loading on spinal shrinkage during treadmill walking.
AB  - INTRODUCTION: Everyday activities such as walking may elicit spinal shrinkage in
      an order of magnitude that has been related to lower back pain. The present study
      aims to compare the effects of unloaded treadmill walking with walking carrying
      loads representing everyday shopping tasks. MATERIALS AND METHODS: Walking tasks
      were performed on seven healthy males and motion analysis was used to track four
      reflective markers at 100 Hz, dividing the spine into three segments. Static data
      was collected in 5-min intervals over a 30-min period. RESULTS: Total spinal
      length and lumbar segment decreased with respect to time (p < 0.001). Load
      affected the percentage length change at each spinal segment (p < 0.005), with
      the lumbar segment showing greatest height loss at the highest load. The upper
      and lower thoracic segments showed greater anterior lean with the heavier loads
      (p = 0.000) and the lumbar segment showed the opposite trend (p = 0.000).
      CONCLUSION: Results suggest that the body adopts less anterior lean with an
      immediate load-bearing demand, to decrease the necessary extension moment
      generated by the spinal extensors for spinal stability. Further postural
      alteration in the same direction is observed with prolonged loading. In
      combination with lumbar spinal shrinkage, such postural changes are likely to
      increase the loading on the facet joints and subsequently unload the discs which
      may be beneficial for those with low back pain.

PMID- 22644434
TI  - Influence of lumbar intervertebral disc degeneration on the outcome of total
      lumbar disc replacement: a prospective clinical, histological, X-ray and MRI
      investigation.
AB  - INTRODUCTION: The role of fusion of lumbar motion segments for the treatment of
      axial low back pain (LBP) from lumbar degenerative disc disease (DDD) without any
      true deformities or instabilities remains controversially debated. In an attempt
      to avoid previously published and fusion-related negative side effects, motion
      preserving technologies such as total lumbar disc replacement (TDR) have been
      introduced. The adequate extent of preoperative DDD for TDR remains unknown, the
      number of previously published studies is scarce and the limited data available
      reveal contradictory results. The goal of this current analysis was to perform a
      prospective histological, X-ray and MRI investigation of the index-segment's
      degree of DDD and to correlate these data with each patient's pre- and
      postoperative clinical outcome parameters from an ongoing prospective clinical
      trial with ProDisc II (Synthes, Paoli, U.S.A.). MATERIALS AND METHODS: Nucleus
      pulposus (NP) and annulus fibrosus (AF) changes were evaluated according to a
      previously validated quantitative histological degeneration score (HDS). X-ray
      evaluation included assessment of the mean, anterior and posterior disc space
      height (DSH). MRI investigation of DDD was performed on a 5-scale grading system.
      The prospective clinical outcome assessment included visual analogue scale (VAS),
      Oswestry Disability Index (ODI) scores as well as the patient's subjective
      satisfaction rates. RESULTS: Data from 51 patients with an average follow-up of
      50.5 months (range 6.1-91.9 months) were included in the study. Postoperative VAS
      and ODI scores improved significantly in comparison to preoperative levels (p <
      0.002). A significant correlation and interdependence was established between
      various parameters of DDD preoperatively (p < 0.05). Degenerative changes of NP
      tissue samples were significantly more pronounced in comparison to those of AF
      material (p < 0.001) with no significant correlation between each other (p >
      0.05). Preoperatively, the extent of DDD was not significantly correlated with
      the patient's symptomatology (p > 0.05). No negative influence was associated
      with increasing stages of DDD on the postoperative clinical outcome parameters
      following TDR (p > 0.05). Increasing stages of DDD in terms of lower DSH scores
      were not associated with inferior clinical results as outlined by postoperative
      VAS or ODI scores or the patient's subjective outcome evaluation at the last FU
      examination (p > 0.05). Conversely, some potential positive effects on the
      postoperative outcome were observed in patients with advanced stages of
      preoperative DDD. Patients with more severe preoperative HDS scores of NP samples
      demonstrated significantly lower VAS scores during the early postoperative course
      (p = 0.02). CONCLUSION: Increasing stages of DDD did not negatively impact on the
      outcome following TDR in a highly selected patient population. In particular, no
      preoperative DDD threshold value was identified from which an inferior
      postoperative outcome could have been deduced. Conversely, some positive effects
      on the postoperative outcome were detected in patients with advanced stages of
      DDD. Combined advantageous effects of progressive morphological structural
      rigidity of the index segment and restabilizing effects from larger distraction
      in degenerated segments may compensate for increasing axial rotational
      instability, one of TDR's perceived disadvantages. Our data reveal a "therapeutic
      window" for TDR in a cohort of patients with various stages of DDD as long as
      preoperative facet joint complaints or degenerative facet arthropathies can be
      excluded and stringent preoperative decision making criteria are adhered to.
      Previously published absolute DSH values as contraindication against TDR should
      be reconsidered.

PMID- 22644438
TI  - H3S2 (3 hooks, 2 screws) construct: a simple growing rod technique for early
      onset scoliosis.
AB  - PURPOSE: The purpose of this study was to review the preliminary results of an
      original fusionless method of treatment for progressive scoliosis in young
      children. METHODS: This study retrospectively reviewed the clinical records and
      radiographs of 23 children with progressive scoliosis who failed to respond to
      conservative treatment and underwent fusionless surgery using a single solid
      growing rod construct. All of them were ambulatory and had a follow-up of minimum
      2 years. Sixteen patients were treated by consecutive distraction of a single
      intramuscular rod, and seven patients with rodding and anterior apical convex
      fusion. The etiology of the scoliosis included 11 idiopathic, 6 syndromic, 4
      congenital, and 2 neurofibromatosis. At initial surgery, the average age was 9.3
      +/- 2.8 years, with a mean Cobb angle of 68 degrees  +/- 32 degrees . Six
      patients underwent progressive scoliosis correction in a Stagnara cast prior to
      surgery, and one patient with an external halo-pelvic Ilizarov device. RESULTS:
      Fusionless single rodding allowed to maintain scoliosis correction in all
      patients. At an average of 3.5 +/- 0.9 years after initial surgery, the 23
      patients showed a correction of 57 % in the magnitude of the original curvature.
      Trunk height increase was documented in all patients and ranged from 1.5 to 11.9
      cm. Rod failure was found in three patients and two patients had hardware
      infection. Only four cases of proximal junctional kyphosis were found at last
      follow-up. CONCLUSIONS: Preliminary results from these series of patients show
      that the presented fusionless single growing rod technique allows to maintain
      correction of progressive early onset scoliosis while permitting spinal growth,
      with low complication rate. With this technique, lengthening procedures are used
      only once in every 10 months and patients are more comfortable as no brace is
      needed in most cases. This technique does not require any specific spine device.
      The procedure is simple and efficacious as long as some guidelines are respected.

PMID- 22644439
TI  - Overexpression of CaTLP1, a putative transcription factor in chickpea (Cicer
      arietinum L.), promotes stress tolerance.
AB  - Dehydration is the most crucial environmental constraint on plant growth and
      development, and agricultural productivity. To understand the underlying
      mechanism of stress tolerance, and to identify proteins for improving such
      important trait, we screened the dehydration-responsive proteome of chickpea and
      identified a tubby-like protein, referred to as CaTLP1. The CaTLP1 was found to
      predominantly bind to double-stranded DNA but incapable of transcriptional
      activation. We investigated the gene structure and organization and demonstrated,
      for the first time, that CaTLP1 may be involved in osmotic stress response in
      plants. The transcripts are strongly expressed in vegetative tissues but weakly
      in reproductive tissues. CaTLP1 is upregulated by dehydration and high salinity,
      and by treatment with abscisic acid (ABA), suggesting that its stress-responsive
      function might be associated with ABA-dependent network. Overexpression of CaTLP1
      in transgenic tobacco plants conferred dehydration, salinity and oxidative stress
      tolerance along with improved shoot and root architecture. Molecular genetic
      analysis showed differential expression of CaTLP1 under normal and stress
      condition, and its preferential expression in the nucleus might be associated
      with enhanced stress tolerance. Our work suggests important roles of CaTLP1 in
      stress response as well as in the regulation of plant development.

PMID- 22644440
TI  - A novel rhodanese is required to maintain chloroplast translation in
      Chlamydomonas.
AB  - Rhodanese-domain proteins (RDPs) are widespread in plants and other organisms,
      but their biological roles are mostly unknown. Here we report on a novel RDP from
      Chlamydomonas that has a single rhodanese domain, and a predicted chloroplast
      transit peptide. The protein was produced in Escherichia coli with a His-tag, but
      lacking most of the N-terminal transit peptide, and after purification was found
      to have rhodanese activity in vitro. It was also used to elicit antibodies for
      western blot analysis, which showed that the native Chlamydomonas protein
      migrated slower on SDS gels (apparent M(r) =34 kDa) than its predicted size (27
      kDa), and co-fractionated with chloroplasts. To assess function in vivo, the
      tandem-RNAi approach was used to generate Chlamydomonas strains that had
      reductions of 30-70% for the mRNA and ~20-40% for the 34-kDa protein. These
      strains showed reduced growth under all trophic conditions, and were sensitive to
      even moderate light; properties reminiscent of chloroplast translation mutants.
      Pulse-labeling in the presence of cycloheximide indicated that chloroplast
      protein synthesis was broadly reduced in the RNAi strains, and transcript
      analysis (by RT-PCR and northern blotting) indicated the effect was mainly
      translational. These results identify a novel rhodanese-like protein that we have
      named CRLT, because it is required to maintain chloroplast translation.

PMID- 22644441
TI  - Ds transposon is biased towards providing splice donor sites for exonization in
      transgenic tobacco.
AB  - Insertion of transposed elements into introns can lead to their activation as
      alternatively spliced cassette exons, an event called exonization, which can
      enrich the complexity of transcriptomes and proteomes. In this study, the first
      exonization event was detected when the modified rice EPSPS marker gene was
      inserted with the Ac transposon 5' end, which provided a splice donor site to
      yield abundant novel transcripts. To assess the contribution of splice donor and
      acceptor sites of transposon sequences, we inserted a Ds element into each intron
      of the EPSPS marker gene. This process yielded 14 constructs, with the Ds
      transposon inserted in the forward and reverse direction in each of the 7 introns
      of the EPSPS marker gene. The constructs were transformed into tobacco plants,
      and novel transcripts were identified by RT-PCR with specific primers.
      Exonization of Ds in EPSPS was biased towards providing splice donor sites of the
      inserted Ds sequence. Additionally, when the Ds inserted in reverse direction, a
      continuous splice donor consensus region was determined by offering 4 donor sites
      in the same intron. Information on these exonization events may help enhance gene
      divergence and functional genomic studies.

PMID- 22644442
TI  - Functional screening of cDNA library from a salt tolerant rice genotype Pokkali
      identifies mannose-1-phosphate guanyl transferase gene (OsMPG1) as a key member
      of salinity stress response.
AB  - Salinity, one of the most deleterious stresses, affects growth and overall yield
      of crop plants. To identify new "candidate genes" having potential role in
      salinity tolerance, we have carried out 'functional screening' of a cDNA library
      (made from a salt tolerant rice-Pokkali). Based on this screening, we identified
      a cDNA clone that was allowing yeast cells to grow in the presence of 1.2 M NaCl.
      Sequencing and BLAST search identified it as mannose-1-phosphate guanyl
      transferase (OsMPG1) gene from rice. Analysis of rice genome sequence database
      indicated the presence of 3 additional genes for MPG. Out of four, three MPG
      genes viz. OsMPG1, 3 and 4 were able to functionally complement yeast MPG mutant 
      YDL055C. We have carried out detailed transcript profiling of all members of MPG
      family by qRT-PCR using two contrasting rice genotypes (IR64 and Pokkali) under
      different abiotic stresses (salinity, drought, oxidative stress, heat stress,
      cold or UV light). These MPG genes showed differential expression under various
      abiotic stresses with two genes (OsMPG1 and 3) showing high induction in response
      to multiple stresses. Analysis of rice microarray data indicated higher
      expression levels for OsMPG1 in specific tissues such as roots, leaves, shoot
      apical meristem and different stages of panicle and seed development, thereby
      indicating its developmental regulation. Functional validation of OsMPG1 carried
      out by overexpression in the transgenic tobacco revealed its involvement in
      enhancing salinity stress tolerance.

PMID- 22644443
TI  - OsYSL16 plays a role in the allocation of iron.
AB  - Graminaceous plants acquire iron by secreting mugineic acid family
      phytosiderophores into the rhizosphere and taking up complexes of iron and
      phytosiderophores through YSL (yellow stripe 1-like) transporters. Rice OsYSL15
      is a transporter of the iron(III)-2'-deoxymugineic acid complex. OsYSL16 has 85 %
      similarity to both OsYSL15 and the iron(II)-nicotianamine transporter OsYSL2. In
      the present study, we show that OsYSL16 functionally complemented a yeast mutant
      defective in iron uptake when grown on medium containing iron(III)-deoxymugineic
      acid, but not when grown on medium containing iron(II)-nicotianamine. OsYSL16
      knockdown seedlings were smaller than wild-type seedlings when only
      iron(III)chloride was supplied as an iron source. The iron concentration in
      shoots of OsYSL16-knockdown plants was similar to that of the wild type; however,
      they showed more severe chlorosis than wild-type plants under iron-deficient
      conditions. Furthermore, OsYSL16-knockdown plants accumulated more iron in the
      vascular bundles of the leaves. Expression of the OsYSL16 promoter fused to the
      beta-glucuronidase gene showed that OsYSL16 is expressed in the root epidermis
      and vascular bundles of whole plants. The expression was typically observed
      around the xylem. In the vascular bundles of unelongated nodes, it was detected
      in the xylem of old leaves and the phloem of new leaves. Graminaceous plants
      translocate iron from the roots to old leaves mainly via the xylem and to new
      leaves mainly via the phloem. Our results suggest that OsYSL16 plays a role in
      the allocation of iron(III)-deoxymugineic acid via the vascular bundles.

PMID- 22644444
TI  - Capillary bending of Janus carbon nanotube micropillars.
AB  - We present a scalable process for the fabrication of slanted carbon nanotube
      micropillar arrays by inclined metal deposition and capillary self-assembly.
      Local control of the micropillar angle from vertical to nearly horizontal is
      achieved, and is explained using a finite element model. These structures may be
      useful for microscale contacts and anisotropic smart surfaces.

PMID- 22644445
TI  - Modeling the cost-effectiveness of strategies for treating esophageal
      adenocarcinoma and high-grade dysplasia.
AB  - OBJECTIVE: This study aims to synthesize cost and health outcomes for current
      treatment pathways for esophageal adenocarcinoma and high-grade dysplasia (HGD)
      and to model comparative net clinical and economic benefits of alternative
      management scenarios. METHODS: A decision-analytic model of real-world practices
      for esophageal adenocarcinoma treatment by tumor stage was constructed and
      validated. The model synthesized treatment probabilities, survival, quality of
      life, and resource use extracted from epidemiological datasets, published
      literature, and expert opinion. Comparative analyses between current practice and
      five hypothetical scenarios for modified treatment were undertaken. RESULTS: Over
      5 years, outcomes across T stage ranged from 4.06 quality-adjusted life-years and
      costs of $3,179 for HGD to 1.62 quality-adjusted life-years and costs of $50,226
      for stage T4. Greater use of endoscopic mucosal resection for stage T1 and
      measures to reduce esophagectomy mortality to 0-3 % produced modest gains,
      whereas a 20 % reduction in the proportion of patients presenting at stage T3
      produced large incremental net benefits of $4,971 (95 % interval, $1,560-8,368).
      CONCLUSION: These findings support measures that promote earlier diagnosis, such
      as developing risk assessment processes or endoscopic surveillance of Barrett's
      esophagus. Incremental net monetary benefits for other strategies are relatively
      small in comparison to predicted gains from early detection strategies.

PMID- 22644446
TI  - Selective reoperation for locally recurrent or metastatic pancreatic ductal
      adenocarcinoma following primary pancreatic resection.
AB  - BACKGROUND: Resection of certain recurrent malignancies can prolong survival, but
      resection of recurrent pancreatic ductal adenocarcinoma is typically
      contraindicated because of poor outcomes. METHODS: All patients from 1992 to 2010
      with recurrent pancreatic cancer after intended surgical cure were
      retrospectively evaluated. Clinicopathologic features were compared from patients
      who did and did not undergo subsequent reoperation with curative intent to
      identify factors associated with prolonged survival. RESULTS: Twenty-one of 426
      patients (5 %) with recurrent pancreatic cancer underwent potentially curative
      reoperation for solitary local-regional (n = 7) or distant (n = 14) recurrence.
      The median disease-free interval after initial resection among reoperative
      patients was longer for those with lung or local-regional recurrence (52.4 and
      41.1 months, respectively) than for those with liver recurrence (7.6 months, p =
      0.006). The median interval between reoperation and second recurrence was longer
      in patients with lung recurrence (median not reached) than with liver or local
      regional recurrence (6 and 9 months, respectively, p = 0.023). Reoperative
      patients with an initial disease-free interval >20 months had a longer median
      survival than those who did not (92.3 versus 31.3 months, respectively; p =
      0.033). CONCLUSION: Patients with a solitary pulmonary recurrence of pancreatic
      cancer after a prolonged disease-free interval should be considered for
      reoperation, as they are more likely to benefit from resection versus other sites
      of solitary recurrence.

PMID- 22644447
TI  - Role of operative therapy in non-cirrhotic patients with metastatic
      hepatocellular carcinoma.
AB  - INTRODUCTION: We investigated the role of operative therapy in non-cirrhotic
      patients who developed metastatic hepatocellular carcinoma (HCC). METHODS: This
      retrospective cohort study included consecutive non-cirrhotic patients with
      metastatic HCC after a prior hepatectomy treated between 1990 and 2009. Patients
      were stratified by operative therapy (resection, ablation, transcatheter
      therapy). Kaplan-Meier analyses with log-rank comparisons tested effects of
      operative therapy on overall survival (OS) and progression-free survival (PFS).
      RESULTS: Of 195 non-cirrhotic patients treated for HCC during the study period,
      98 [median age 65, interquartile range (IQR) 53-71; 55 % male] subsequently
      developed metastatic HCC (55 intrahepatic only). Median time to development of
      metastases after the index operation was 10 months (IQR 5-20 months); median
      number of metastases was 3 (IQR 2-7). Half of these patients (n = 50) underwent
      operative treatment of metastases; 20 (40 %) underwent metastasectomy, 18 (36 %)
      ablation, and 12 (24 %) transcatheter therapy. Operative therapy was associated
      with improved OS (p < 0.001). Resection or ablation was associated with improved
      PFS and OS compared to transcatheter therapy (all p <= 0.006). Nine patients
      (seven resection, two ablation) are disease free at a median of 50 months (IQR 24
      80 months) posttreatment. CONCLUSIONS: Resection and ablation are associated with
      an improved PFS and long-term OS and should be considered in select patients with
      metastatic HCC.

PMID- 22644449
TI  - Intraocular pressure elevation after Descemet's stripping endothelial
      keratoplasty.
AB  - PURPOSE: To investigate the incidence of intraocular pressure (IOP) elevation
      after Descemet's stripping endothelial keratoplasty (DSEK) and associated
      clinical findings. METHODS: Forty-eight eyes of 46 patients who underwent DSEK
      were studied in this single-center retrospective study. IOP elevation was defined
      as the presence of an increase in IOP above 21 mmHg lasting at least two months,
      the need to introduce topical/oral antiglaucoma medications for at least two
      months, and the need for surgical therapy for uncontrolled IOP. Patients with pre
      existing glaucoma or patients who were using antiglaucoma drugs before DSEK were
      excluded according to the protocol of the study. The incidence of post-DSEK IOP
      elevation was investigated. RESULTS: The incidence of IOP elevation after DSEK
      was 16.7 %. Glaucoma therapy following DSEK was needed in eight eyes of eight
      patients. IOP elevations were diagnosed from two to ten months after DSEK. There
      was no statistical difference in the survival probabilities of patients with
      different preoperative diagnoses. Pre-op IOP was observed to be a risk factor of
      IOP elevation in this series. CONCLUSIONS: IOP elevation appears to be a common
      postoperative complication of DSEK. Patients without preexisting glaucoma but
      with higher pre-op IOP need to be followed up carefully after DSEK.

PMID- 22644450
TI  - The usefulness of infraorbital nerve enlargement on MRI imaging in clinical
      diagnosis of IgG4-related orbital disease.
AB  - PURPOSE: To investigate the frequency of infraorbital nerve enlargement (IONE) in
      orbital lymphoproliferative disorders, and to show that IONE can contribute to
      the clinical diagnosis of IgG4-related orbital diseases (IgG4-ROD). SUBJECTS AND
      METHODS: 71 cases in which orbital lymphoproliferative disorders were diagnosed
      at Okayama Medical Center and Mitoyo General Hospital from April, 2004 to March,
      2011 were investigated. The male-to-female ratio was 39:32, and the age range 27
      87 years old (average age 64.1 years). Whenever the coronal section of the
      infraorbital nerve was larger than that of the optic nerve on MRI, it was defined
      as IONE. RESULTS: The breakdown of the 71 cases was: 45 cases of non-Hodgkin
      lymphoma, 16 cases of IgG4-ROD, 5 cases of reactive lymphoid hyperplasia, and 5
      cases of idiopathic orbital inflammation. Of these, a total of 9 cases had IONE.
      The incidence of IONE was compared between the IgG4-ROD patient group and the non
      IgG4-ROD patient group and was significantly higher in the IgG4-ROD patient group
      (p < 0.0001). CONCLUSION: If IONE is observed in a case of orbital
      lymphoproliferative disorders on MRI, then it is highly possible that such a case
      is IgG4-ROD.

PMID- 22644448
TI  - Retinal remodeling.
AB  - Retinal photoreceptor degeneration takes many forms. Mutations in rhodopsin genes
      or disorders of the retinal pigment epithelium, defects in the adenosine
      triphosphate binding cassette transporter, ABCR gene defects, receptor tyrosine
      kinase defects, ciliopathies and transport defects, defects in both transducin
      and arrestin, defects in rod cyclic guanosine 3',5'-monophosphate
      phosphodiesterase, peripherin defects, defects in metabotropic glutamate
      receptors, synthetic enzymatic defects, defects in genes associated with
      signaling, and many more can all result in retinal degenerative disease like
      retinitis pigmentosa (RP) or RP-like disorders. Age-related macular degeneration
      (AMD) and AMD-like disorders are possibly due to a constellation of potential
      gene targets and gene/gene interactions, while other defects result in diabetic
      retinopathy or glaucoma. However, all of these insults as well as traumatic
      insults to the retina result in retinal remodeling. Retinal remodeling is a
      universal finding subsequent to retinal degenerative disease that results in
      deafferentation of the neural retina from photoreceptor input as downstream
      neuronal elements respond to loss of input with negative plasticity. This
      negative plasticity is not passive in the face of photoreceptor degeneration,
      with a phased revision of retinal structure and function found at the molecular,
      synaptic, cell, and tissue levels involving all cell classes in the retina,
      including neurons and glia. Retinal remodeling has direct implications for the
      rescue of vision loss through bionic or biological approaches, as circuit
      revision in the retina corrupts any potential surrogate photoreceptor input to a
      remnant neural retina. However, there are a number of potential opportunities for
      intervention that are revealed through the study of retinal remodeling, including
      therapies that are designed to slow down photoreceptor loss, interventions that
      are designed to limit or arrest remodeling events, and optogenetic approaches
      that target appropriate classes of neurons in the remnant neural retina.

PMID- 22644452
TI  - Protein aggregation: The secret recipe for RNA granules.

PMID- 22644453
TI  - Goodbye homunculus.

PMID- 22644451
TI  - Does nausea and vomiting of pregnancy play a role in the association found
      between maternal caffeine intake and fetal growth restriction?
AB  - The aim of this study was to explore the relationships between nausea and
      vomiting in pregnancy and (a) fetal growth restriction; and (b) maternal caffeine
      metabolism and fetal growth restriction. A cohort of 2,643 pregnant women, aged
      18-45 years, attending two UK maternity units between 8 and 12 weeks gestation,
      was recruited. A validated tool assessed caffeine intake at different stages of
      pregnancy and caffeine metabolism was assessed from a caffeine challenge test.
      Experience of nausea and vomiting of pregnancy was self-reported for each
      trimester. Adjustment was made for confounders, including salivary cotinine as a
      biomarker of current smoking status. There were no significant associations
      between fetal growth restriction and nausea and vomiting in pregnancy, even after
      adjustment for smoking and alcohol intake. There were no significant differences
      in the relationship between caffeine intake and fetal growth restriction between
      those experiencing symptoms of nausea and vomiting and those who did not, for
      either the first (p = 0.50) or second trimester (p = 0.61) after adjustment for
      smoking, alcohol intake and caffeine half-life. There were also no significant
      differences in the relationship between caffeine half-life and fetal growth
      restriction between those experiencing symptoms of nausea and vomiting and those
      who did not, for either the first trimester (p = 0.91) or the second trimester (p
      = 0.45) after adjusting for smoking, alcohol intake and caffeine intake. The
      results from this study show no evidence that the relationship between maternal
      caffeine intake and fetal growth restriction is modified by nausea and vomiting
      in pregnancy.

PMID- 22644454
TI  - Cardiac arrest following ketamine administration for rapid sequence intubation.
AB  - Given their relative hemodynamic stability, ketamine and etomidate are commonly
      chosen anesthetic agents for sedation during the endotracheal intubation of
      critically ill patients. As the use of etomidate has come into question
      particularly in patients with sepsis, due to its effect of adrenal suppression,
      there has been a shift in practice with more reliance on ketamine. However, as
      ketamine relies on a secondary sympathomimetic effect for its cardiovascular
      stability, cardiovascular and hemodynamic compromise may occur in patients who
      are catecholamine depleted. We present 2 critically ill patients who experienced
      cardiac arrest following the administration of ketamine for rapid sequence
      intubation (RSI). The literature regarding the use of etomidate and ketamine for
      RSI in critically ill patients is reviewed and options for sedation during
      endotracheal intubation in this population are discussed. 

PMID- 22644455
TI  - Tracheobronchomegaly following intrauterine tracheal occlusion for congenital
      diaphragmatic hernia.
AB  - BACKGROUND: Fetuses with severe congenital diaphragmatic hernia (CDH) and
      pulmonary hypoplasia may benefit from fetal endoluminal tracheal occlusion
      (FETO). Enlargement of the main bronchi and trachea appears to be a common
      complication of FETO. OBJECTIVE: To retrospectively evaluate the trachea and main
      bronchi of infants who underwent FETO for CDH and compare diameters with age
      matched references. MATERIAL AND METHODS: Postnatal and follow-up chest
      radiographs were performed in seven children with unilateral CDH treated by FETO.
      Additional CT was performed in six of these (one neonate died before CT could be
      performed). Images were acquired from 3 days to 23 months of age. For each child,
      radiographs and CT images with optimal visualisation of the airways were selected
      for retrospective analysis. Tracheal and bronchial morphology was assessed by two
      experienced paediatric radiologists, and the diameters of these structures
      measured and compared with age-matched references. RESULTS: Mean diameters of the
      trachea and main bronchi were above the age-matched normal range in all patients,
      regardless of the side of the hernia or the degree of lung hypoplasia.
      CONCLUSION: Enlargement of the trachea and main bronchi appears following FETO
      and persists at least to the age of 5 years.

PMID- 22644456
TI  - CT features of lymphobronchial tuberculosis in children, including complications
      and associated abnormalities.
AB  - BACKGROUND: Lymphobronchial tuberculosis (TB) is tuberculous lymphadenopathy
      involving the airways, which is particularly common in children. OBJECTIVE: To
      describe CT findings of lymphobronchial TB in children, the parenchymal
      complications and associated abnormalities. MATERIALS AND METHODS: CT scans of
      children with lymphobronchial TB were reviewed retrospectively. Lymphadenopathy,
      bronchial narrowing, parenchymal complications and associations were documented.
      RESULTS: Infants comprised 51% of patients. The commonest site of lymphadenopathy
      was the subcarinal mediastinum (97% of patients). Bronchial compression was seen
      in all children (259 bronchi, of these 28% the bronchus intermedius) with severe
      or complete stenosis in 23% of affected bronchi. Parenchymal complications were
      present in 94% of patients, including consolidation (88%), breakdown (42%), air
      trapping (38%), expansile pneumonia (28%), collapse (17%) and bronchiectasis
      (9%), all predominantly on the right side (63%). Associated abnormalities
      included ovoid lesions, miliary nodules, pleural disease and intracavitary
      bodies. CONCLUSION: Airway compression was more severe in infants and most
      commonly involved the bronchus intermedius. Numerous parenchymal complications
      were documented, all showing right-side predominance.

PMID- 22644461
TI  - From the editors' desk: Cognitive errors, and why we may or may not be as smart
      as we think we are (or would like to be).

PMID- 22644462
TI  - Outcomes for resident-identified high-risk patients and resident perspectives of
      year-end continuity clinic handoffs.
AB  - BACKGROUND: Many patients nationwide change their primary care physician (PCP)
      when internal medicine (IM) residents graduate. Few studies have examined this
      handoff. OBJECTIVE: To assess patient outcomes and resident perspectives after
      the year-end continuity clinic handoff DESIGN: Retrospective cohort PARTICIPANTS:
      Patients who underwent a year-end clinic handoff in July 2010 and a comparison
      group of all other resident clinic patients from 2009-2011. PGY2 IM residents
      surveyed from 2010-2011. MEASUREMENTS: Percent of high-risk patients after the
      clinic handoff scheduled for an appointment, who saw their assigned PCP, lost to
      follow-up, or had an acute visit (ED or hospitalization). Perceptions of PGY2 IM
      residents surveyed after receiving a clinic handoff. RESULTS: Thirty graduating
      residents identified 258 high-risk patients. While nearly all patients (97 %)
      were scheduled, 29 % missed or cancelled their first new PCP visit. Only 44 % of
      patients saw the correct PCP and six months later, one-fifth were lost to follow
      up. Patients not seen by a new PCP after the handoff were less likely to have
      appropriate follow-up for pending tests (0 % vs. 63 %, P<0.001). A higher mean no
      show rate (NSR) was observed among patients who missed their first new PCP visit
      (22 % vs. 16 % NSR, p<0.001) and those lost to follow-up (21 % vs. 17 % NSR,
      p=0.019). While 47 % of residents worried about missing important data during the
      handoff, 47 % reported that they do not perceive patients as "theirs" until they
      are seen by them in clinic. CONCLUSIONS: While most patients were scheduled for
      appointments after a clinic handoff, many did not see the correct resident and
      one-fifth were lost to follow-up. Patients who miss appointments are especially
      at risk of poor clinic handoff outcomes. Future efforts should improve patient
      attendance to their first new PCP visit and increase PCP ownership.

PMID- 22644463
TI  - Maternal psychological distress and parenting stress after gastrostomy placement
      in children.
AB  - OBJECTIVES: The aim of the study was to evaluate stress in mothers of children
      with feeding problems before and after gastrostomy placement, and to identify
      changes in child health and variables affecting maternal stress. METHODS:
      Psychological distress and parenting stress in 34 mothers of children referred
      for gastrostomy were assessed using general health questionnaire (GHQ) (overall
      psychological distress), impact of event scale (IES) (intrusive stress related to
      child's feeding problems), and parenting stress index (PSI) (stress related to
      parenting) before, 6, and 18 months after placement of a gastrostomy. Information
      of child health and long-term gastrostomy complications were recorded. A
      semistructured interview constructed for the present study explored maternal
      preoperative expectations and child's quality of life. RESULTS: Insertion of a
      gastrostomy did not significantly influence vomiting or the number of children
      with a low weight-for-height percentile. All of the children experienced
      peristomal complications. Despite this, mothers' overall psychological distress
      was significantly reduced after 6 and 18 months, and the majority of mothers
      (85%) reported that their preoperative expectations were fulfilled and that the
      child's quality of life was improved after gastrostomy placement. Maternal
      concerns for the child's feeding problems, measured as intrusive stress, had
      effect on maternal overall psychological distress. CONCLUSIONS: Despite frequent
      stomal complications the gastrostomy significantly reduced the mothers'
      psychological distress and improved the child's quality of life as reported by
      the mother.

PMID- 22644464
TI  - Autoimmune hepatitis in children in Eastern Denmark.
AB  - OBJECTIVES: Autoimmune hepatitis (AIH) in childhood is a progressive chronic
      inflammatory liver disease. The aim of this study was to compare the clinical and
      biochemical characteristics of 33 paediatric patients diagnosed as having AIH
      with earlier described cohorts, and to examine the effect of early treatment
      strategies on the course of disease. METHODS: A population-based cohort of
      patients from January 1993 to September 2009 was identified prospectively, and
      the patient data were collected by a retrospective examination of the files.
      RESULTS: Twenty-nine patients had type 1 AIH, 2 had type 2, and 2 could not be
      categorised. Among the 33 children, 16 (48.5%) were girls and 17 (51.5%) were
      boys. Twenty-three (69.7%) of the patients had symptoms at presentation
      indistinguishable from acute viral hepatitis, but in 16 (69.6%) of those the
      liver biopsy showed cirrhosis. Twenty (60.6%) patients were treated with
      prednisolone and azathioprine at the time of remission, whereas 8 (24.2%) were
      treated with prednisolone. One (3%) patient did not experience remission during
      the observation period. CONCLUSIONS: The patients in our study appeared similar
      to previously published cohorts, although a female predominance was not observed.
      Our data suggest that early treatment including both prednisolone and
      azathioprine could be more effective than prednisolone alone, even if randomised
      controlled paediatric studies comparing these 2 different treatment regimens are
      needed.

PMID- 22644465
TI  - Management of autoimmune hepatitis in children:  how many steps away from common
      agreement?

PMID- 22644466
TI  - Workshop report:  developing a pediatric inflammatory bowel diseases network and
      data platform in Canada.
AB  - The purpose of the workshop was to receive input from the Canadian pediatric
      inflammatory bowel diseases research community to develop a research funding
      opportunity for a Canadian pediatric inflammatory bowel diseases network and data
      platform supported by the Canadian Institutes for Health Research, in partnership
      with the Foundation for Children with Intestinal and Liver Disorders. Leaders
      from across the country came together, with the objectives of identifying the
      scientific goals for a Canadian pediatric inflammatory bowel disease network, the
      required infrastructure, and an appropriate governance structure needed to
      achieve such a network and data platform, as well as other elements needed to
      ensure the successful implementation of a network.

PMID- 22644467
TI  - Commentaries on "Workshop report: developing a pediatric inflammatory bowel
      diseases network and data platform in Canada": international networking in
      pediatric gastroenterology research: advancing science and medicine with
      collaborative efforts.

PMID- 22644468
TI  - Commentaries on "Workshop report: developing a pediatric inflammatory bowel
      diseases network and data platform in Canada": collaboration and networking: the
      name of the game in pediatric inflammatory bowel disease.

PMID- 22644469
TI  - Commentaries on "Workshop report: developing a pediatric inflammatory bowel
      diseases network and data platform in Canada": networking in pediatric
      inflammatory bowel disease: the French GETAID Pediatrique experience.

PMID- 22644470
TI  - Commentaries on "Workshop report: developing a pediatric inflammatory bowel
      diseases network and data platform in Canada": collaborative chronic care network
      (C3N) of the future.

PMID- 22644471
TI  - Commentaries on "Workshop report: developing a pediatric inflammatory bowel
      diseases network and data platform in Canada": networks of the future.

PMID- 22644472
TI  - Asymmetric Michael addition of boronic acids to a gamma-hydroxy-alpha,beta
      unsaturated aldehyde catalyzed by resin-supported peptide.
AB  - A resin-supported peptide catalyst effective for the asymmetric Michael addition
      of boronic acids to (E)-4-hydroxybut-2-enal was developed. From a spectral study,
      it was revealed that the optimum peptide consisted of both a beta-turn and helix.
      Such a combination of secondary structures was essential for achieving a high
      catalytic ability.

PMID- 22644473
TI  - Are psychopathological features relevant predictors of glucose control in
      patients with type 2 diabetes? A prospective study.
AB  - Type 2 diabetes has been associated with an increased prevalence of
      psychopathology, in comparison with matched non-diabetic controls. However, the
      cross-sectional design of most studies does not allow causal inferences. The aim
      of the present study is the exploration of this possible association in patients
      with type 2 diabetes, in a longitudinal fashion. This prospective observational
      study was conducted on a consecutive series of 250 type 2 diabetic outpatients
      and a 1-year follow-up period was performed. At enrollment, a complete medical
      history was collected and hemoglobin A1c was measured. General psychopathology
      was assessed using the Symptom Checklist 90-revised and the Eating Disorder
      Examination Questionnaire. Among the 187 patients available at follow-up, factors
      associated with unsatisfactory glycemic control at follow-up were baseline
      hemoglobin A1c, insulin therapy, a longer duration of diabetes, higher scores on
      the Eating behavior, and Somatization scales. At multivariate analysis, the
      attainment of hemoglobin A1c <= 7 % was associated with baseline hemoglobin A1c
      (p = 0.01), insulin therapy (p = 0.016), and Eating behavior (p = 0.02), whereas
      duration of diabetes and Somatization were no longer significant after adjusting
      for confounders. The results of the present study suggest that clinical features
      have a much greater impact on attainment of therapeutic goals than
      psychopathology. However, there are several aspects, such as temperament,
      motivation, self-efficacy, and well-being, not assessed in the present study,
      which could be crucial. These areas should be adequately explored for obtaining
      an overall picture of the psychological determinants of appropriate metabolic
      control in diabetes.

PMID- 22644474
TI  - Fungal foray.

PMID- 22644475
TI  - The time course of photoinactivation of photosystem II in leaves revisited.
AB  - Since photosystem II (PS II) performs the demanding function of water oxidation
      using light energy, it is susceptible to photoinactivation during photosynthesis.
      The time course of photoinactivation of PS II yields useful information about the
      process. Depending on how PS II function is assayed, however, the time course
      seems to differ. Here, we revisit this problem by using two additional assays:
      (1) the quantum yield of oxygen evolution in limiting, continuous light and (2)
      the flash-induced cumulative delivery of PS II electrons to the oxidized primary
      donor (P700(+)) in PS I measured as a 'P700 kinetics area'. The P700 kinetics
      area is based on the fact that the two photosystems function in series: when P700
      is completely photo-oxidized by a flash added to continuous far-red light,
      electrons delivered from PS II to PS I by the flash tend to re-reduce P700(+)
      transiently to an extent depending on the PS II functionality, while the far-red
      light photo-oxidizes P700 back to the steady-state concentration. The quantum
      yield of oxygen evolution in limiting, continuous light indeed decreased in a way
      that deviated from a single-negative exponential. However, measurement of the
      quantum yield of oxygen in limiting light may be complicated by changes in
      mitochondrial respiration between darkness and limiting light. Similarly, an
      assay based on chlorophyll fluorescence may be complicated by the varying depth
      in leaf tissue from which the signal is detected after progressive
      photoinactivation of PS II. On the other hand, the P700 kinetics area appears to
      be a reasonable assay, which is a measure of functional PS II in the whole leaf
      tissue and independent of changes in mitochondrial respiration. The P700 kinetics
      area decreased in a single-negative exponential fashion during progressive
      photoinactivation of PS II in a number of plant species, at least at functional
      PS II contents >=6 % of the initial value, in agreement with the conclusion of
      Sarvikas et al. (Photosynth Res 103:7-17, 2010). That is, the single-negative
      exponential time course does not provide evidence for photoprotection of
      functional PS II complexes by photoinactivated, connected neighbours.

PMID- 22644476
TI  - Relationships between the photochemical reflectance index (PRI) and chlorophyll
      fluorescence parameters and plant pigment indices at different leaf growth
      stages.
AB  - This study aimed to evaluate the photochemical reflectance index (PRI) for
      assessing plant photosynthetic performance throughout the plant life cycle. The
      relationships between PRI, chlorophyll fluorescence parameters, and leaf pigment
      indices in Solanum melongena L. (aubergine; eggplant) were studied using
      photosynthetic induction curves both in short-term (diurnal) and long-term
      (seasonal) periods under different light intensities. We found good correlations
      between PRI/non-photochemical quenching (NPQ) and PRI/electron transport rate
      (ETR) in the short term at the same site of a single leaf but these relationships
      did not hold throughout the life of the plant. In general, changes in PRI owing
      to NPQ or ETR variations in the short term were <20 % of those that occurred with
      leaf aging. Results also showed that PRI was highly correlated to plant pigments,
      especially chlorophyll indices measured by spectral reflectance. Moreover,
      relationships of steady-state PRI/ETR and steady-state PRI/photochemical yield of
      photosystem II (Phi(PSII)) measured at uniform light intensity at different life
      stages proved that overall photosynthesis capacity and steady-state PRI were
      better correlated through chlorophyll content than NPQ and xanthophylls. The
      calibrated PRI index  accommodated these pigments effects and gave better
      correlation with NPQ and ETR than PRI. Further studies of PRI indices based on
      pigments other than xanthophylls, and studies on PRI mechanisms in different
      species are recommended.

PMID- 22644477
TI  - The reaction center is the sensitive target of the mercury(II) ion in intact
      cells of photosynthetic bacteria.
AB  - The sensitivity of intact cells of purple photosynthetic bacterium Rhodobacter
      sphaeroides wild type to low level (<100 MUM) of mercury (Hg2+) contamination was
      evaluated by absorption and fluorescence spectroscopies of the
      bacteriochlorophyll-protein complexes. All assays related to the function of the
      reaction center (RC) protein (induction of the bacteriochlorophyll fluorescence,
      delayed fluorescence and light-induced oxidation and reduction of the
      bacteriochlorophyll dimer and energization of the photosynthetic membrane) showed
      prompt and later effects of the mercury ions. The damage expressed by decrease of
      the magnitude and changes of rates of the electron transfer kinetics followed
      complex (spatial and temporal) pattern according to the different Hg2+
      sensitivities of the electron transport (donor/acceptor) sites including the
      reduced bound and free cytochrome c2 and the primary reduced quinone. In contrast
      to the RC, the light harvesting system and the bc1 complex demonstrated much
      higher resistance against the mercury pollution. The 850 and 875 nm components of
      the peripheral and core complexes were particularly insensitive to the
      mercury(II) ions. The concentration of the photoactive RCs and the connectivity
      of the photosynthetic units decreased upon mercury treatment. The degree of
      inhibition of the photosynthetic apparatus was always higher when the cells were
      kept in the light than in the dark indicating the importance of metabolism in
      active transport of the mercury ions from outside to the intracytoplasmic
      membrane. Any of the tests applied in this study can be used for detection of
      changes in photosynthetic bacteria at the early stages of the action of
      toxicants.

PMID- 22644478
TI  - Protecting effect of phosphorylation on oxidative damage of D1 protein by down
      regulating the production of superoxide anion in photosystem II membranes under
      high light.
AB  - The physiological significance of photosystem II (PSII) core protein
      phosphorylation has been suggested to facilitate the migration of oxidative
      damaged D1 and D2 proteins, but meanwhile the phosphorylation seems to be
      associated with the suppression of reactive oxygen species (ROS) production, and
      it also relates to the degradation of PSII reaction center proteins. To more
      clearly elucidate the possible protecting effect of the phosphorylation on
      oxidative damage of D1 protein, the degradation of oxidized D1 protein and the
      production of superoxide anion in the non-phosphorylated and phosphorylated PSII
      membranes were comparatively detected using the Western blotting and electron
      spin resonance spin-trapping technique, respectively. Obviously, all of three ROS
      components, including superoxide anion, hydrogen peroxide and hydroxyl radical
      are responsible for the degradation of oxidized D1 protein, and the protection of
      the D1 protein degradation by phosphorylation is accompanied by the inhibition of
      superoxide anion production. Furthermore, the inhibiting effect of 3-(3,4
      dichlorophenyl)-1,1-dimethylurea (DCMU), a competitor to Q(B), on superoxide
      anion production and its protecting effect on D1 protein degradation are even
      more obvious than those of phosphorylation. Both DCMU effects are independent of
      whether PSII membranes are phosphorylated or not, which reasonably implies that
      the herbicide DCMU and D1 protein phosphorylation probably share the same target
      site in D1 protein of PSII. So, altogether it can be concluded that the
      phosphorylation of D1 protein reduces the oxidative damage of D1 protein by
      decreasing the production of superoxide anion in PSII membranes under high light.

PMID- 22644479
TI  - Oxygen evolution and chlorophyll fluorescence from multiple turnover light
      pulses: charge recombination in photosystem II in sunflower leaves.
AB  - Oxygen evolution and Chl fluorescence induction were measured during multiple
      turnover light pulses (MTP) of 630-nm wavelength, intensities from 250 to 8,000
      MUmol quanta m(-2) s(-1) and duration from 0.3 to 200 ms in sunflower leaves at
      22  degrees C. The ambient O(2) concentration was 10-30 ppm and MTP were applied
      after pre-illumination under far-red light (FRL), which oxidized plastoquinone
      (PQ) and randomized S-states because of the partial excitation of PSII. Electron
      (e ( - )) flow was calculated as 4.O(2) evolution. Illumination with MTP of
      increasing length resulted in increasing O(2) evolution per pulse, which was
      differentiated against pulse length to find the time course of O(2) evolution
      rate with sub-millisecond resolution. Comparison of the quantum yields, Y (IIO) =
      e ( - )/hnu from O(2) evolution and Y (IIF) = (F (m) - F)/F (m) from Chl
      fluorescence, detected significant losses not accompanied by fluorescence
      emission. These quantum losses are discussed to be caused by charge recombination
      between Q (A) (-) and oxidized TyrZ at a rate of about 1,000 s(-1), either
      directly or via the donor side equilibrium complex Q(A) -> P (D1) (+) <->
      TyrZ(ox), or because of cycling facilitated by Cyt b (559). Predicted from the
      suggested mechanism, charge recombination is enhanced by damage to the water
      oxidizing complex and by restricted PSII acceptor side oxidation. The rate of
      PSII charge recombination/cycling is fast enough for being important in
      photoprotection.

PMID- 22644480
TI  - Synaptic plasticity: ARC plays inverse tag at synapses.

PMID- 22644481
TI  - Ion channels: Metabolite targets sodium channels in diabetic pain.

PMID- 22644482
TI  - Volatile emissions from an epiphytic fungus are semiochemicals for eusocial
      wasps.
AB  - Microbes are ubiquitous on plant surfaces. However, interactions between
      epiphytic microbes and arthropods are rarely considered as a factor that affects
      arthropod behaviors. Here, volatile emissions from an epiphytic fungus were
      investigated as semiochemical attractants for two eusocial wasps. The fungus
      Aureobasidium pullulans was isolated from apples, and the volatile compounds
      emitted by fungal colonies were quantified. The attractiveness of fungal colonies
      and fungal volatiles to social wasps (Vespula spp.) were experimentally tested in
      the field. Three important findings emerged: (1) traps baited with A. pullulans
      caught 2750 % more wasps on average than unbaited control traps; (2) the major
      headspace volatiles emitted by A. pullulans were 2-methyl-1-butanol, 3-methyl-1
      butanol, and 2-phenylethyl alcohol; and (3) a synthetic blend of fungal volatiles
      attracted 4,933 % more wasps on average than unbaited controls. Wasps were most
      attracted to 2-methyl-1-butanol. The primary wasp species attracted to fungal
      volatiles were the western yellowjacket (Vespula pensylvanica) and the German
      yellowjacket (V. germanica), and both species externally vectored A. pullulans.
      This is the first study to link microbial volatile emissions with eusocial wasp
      behaviors, and these experiments indicate that volatile compounds emitted by an
      epiphytic fungus can be responsible for wasp attraction. This work implicates
      epiphytic microbes as important components in the community ecology of some
      eusocial hymenopterans, and fungal emissions may signal suitable nutrient sources
      to foraging wasps. Our experiments are suggestive of a potential symbiosis, but
      additional studies are needed to determine if eusocial wasp-fungal associations
      are widespread, and whether these associations are incidental, facultative, or
      obligate.

PMID- 22644483
TI  - Ecophysiology of an ammonia-oxidizing archaeon adapted to low-salinity habitats.
AB  - Ammonia oxidation in marine and terrestrial ecosystems plays a pivotal role in
      the cycling of nitrogen and carbon. Recent discoveries have shown that ammonia
      oxidizing archaea (AOA) are both abundant and diverse in these systems, yet very
      little is known about their physiology. Here we report a physiological analysis
      of a novel low-salinity-type AOA enriched from the San Francisco Bay estuary,
      Candidatus Nitrosoarchaeum limnia strain SFB1. N. limnia has a slower growth rate
      than Nitrosopumilus maritimus and Nitrososphaera viennensis EN76, the only pure
      AOA isolates described to date, but the growth rate is comparable to the growth
      of marine AOA enrichment cultures. The growth rate only slightly decreased when
      N. limnia was grown under lower-oxygen conditions (5.5 % oxygen in the
      headspace). Although N. limnia was capable of growth at 75 % of seawater
      salinity, there was a longer lag time, incomplete oxidation of ammonia to
      nitrite, and slower overall growth rate. Allylthiourea (ATU) only partially
      inhibited growth and ammonia oxidation by N. limnia at concentrations known to
      completely inhibit bacterial ammonia oxidation. Using electron microscopy, we
      confirmed the presence of flagella as suggested by various flagellar biosynthesis
      genes in the N. limnia genome. We demonstrate that N. limnia is representative of
      a low-salinity estuarine AOA ecotype and that more than 85 % of its proteins have
      highest identity to other coastal and estuarine metagenomic sequences. Our
      findings further highlight the physiology of N. limnia and help explain its
      ecological adaptation to low-salinity niches.

PMID- 22644486
TI  - Metformin interacts with AMPK through binding to gamma subunit.
AB  - Metformin acts as an energy regulator by activating 5'-adenosine monophosphate
      activated protein kinase (AMPK), which is a key player in the regulation of
      energy homeostasis, but it is uncertain whether AMPK is its direct target. This
      study aims to investigate the possible interaction between metformin and AMPK.
      First, we verified that metformin can promote AMPK activation and induce ACC
      inactivation in human HepG2 cells using western blot. Then we predicted that
      metformin may interact with the gamma subunit of AMPK by molecular docking
      analysis. The fluorescence spectrum and ForteBio assays indicated that metformin
      has a stronger binding ability to the gamma subunit of AMPK than to alpha
      subunit. In addition, interaction of metformin with gamma-AMPK resulted in a
      decrease in the alpha-helicity determined by CD spectra, but relatively little
      change was seen with alpha-AMPK. These results demonstrate that metformin may
      interact with AMPK through binding to the gamma subunit.

PMID- 22644487
TI  - Regulation of the transcriptional activation of CTRP3 in chondrocytes by c-Jun.
AB  - Although C1qTNF-related protein 3 (CTRP3) is highly expressed in cartilage and is
      involved in the proliferation and migration of chondrocytes, the molecular
      mechanism governing the transcriptional regulation of CTRP3 in chondrocytes is
      largely unknown. Here, we demonstrated the mechanism of transcriptional
      activation of the CTRP3 gene in chondrogenic cells. We observed that c-Jun
      stimulated CTRP3 promoter activity in ATDC5 cells. Deletion analysis of the CTRP3
      promoter showed that the c-Jun-responsive region is localized at the position
      between -359 and -176. Mutation of the AP-1 binding site in this region
      eliminated c-Jun-mediated CTRP3 promoter activity. A promoter enzyme immunoassay
      and a chromatin immunoprecipitation assay showed that c-Jun binds directly to the
      AP-1 binding site at the region -184/-177 of the mouse CTRP3 promoter. Thus,
      these results demonstrated that c-Jun is a cis-acting element for CTRP3
      regulation in chondrogenic cells.

PMID- 22644489
TI  - SHP-2 and PTP-pest induction during Rb-E2F associated apoptosis.
AB  - Apoptosis is intimately connected to cell cycle regulation via the Retinoblastoma
      (Rb)-E2F pathway and thereby serves an essential role in tumor suppression by
      eliminating aberrant hyperproliferative cells. Upon loss of Rb activity, an
      apoptotic response can be elicited through both p53-dependent and p53-independent
      mechanisms. While much of this apoptotic response has been attributed to the
      p19ARF/p53 pathway, increasing evidence has supported the role of protein
      tyrosine phosphatases (PTPs) in contributing to the initiation of the Rb-E2F
      associated apoptotic response. One protein tyrosine phosphatase, PTP-1B, which is
      induced by the Rb-E2F pathway, has been shown to contribute to a p53-independent
      apoptotic pathway by inactivating focal adhesion kinase. This report identifies
      two additional PTPs, SHP-2 and PTP-PEST, that are also directly activated by the
      Rb-E2F pathway and which can contribute to signal transduction during p53
      independent apoptosis.

PMID- 22644490
TI  - [Considerations about health services research].

PMID- 22644491
TI  - [Impending liver failure after chemoimmunotherapy-induced reactivation  of
      hepatitis B - successful treatment with entecavir].
AB  - HISTORY AND CLINICAL FINDINGS: An 83-year old woman had been treated with
      bendamustin and rituximab for prolymphocytic leukemia. Two weeks after cycle 6 of
      chemotherapy, signs and symptoms of a severe hepatitis occurred. INVESTIGATIONS:
      Highly elevated values for AST (1353 U/l) and bilirubin (27.8 mg/dl), impaired
      coagulation parameters (INR 1,68) and the detection of ascites led to the
      diagnosis of an impending liver failure induced by reactivation of a hitherto
      unknown hepatitis B (HBs antigen pos., HBe antigen pos., anti HBc IgG pos., HBV
      DNA 1,65 Mio copies/ml). TREATMENT AND COURSE: After an immediately started
      treatment with entecavir (0.5 mg/d po), symptoms and laboratory parameters
      rapidly improved. 4 months later liver chemistry was completely normal and HBV
      DNA was negative. After 8 months, a seroconversion to anti HBs was noted.
      CONCLUSION: In single cases, life threatening complications of chemotherapy
      induced reactivation of hepatitis B may be successfully treated by potent and
      stabile nucleosidanalogs.

PMID- 22644492
TI  - [84-year-old woman with suspected cardiac decompression].

PMID- 22644493
TI  - [The first 24 hours - the unconscious patient from the neurologist's viewpoint].
AB  - About 50 % of non-traumatic impairments of consciousness are caused by primary
      cerebral diseases such as epilepsy, intracerebral hemorrhage or
      meningoencephalitis. In addition to primary cerebral conditions, internal
      diseases can also lead to focal neurological symptoms or neuroimaging
      abnormalities. Anamnestic informations, body inspection, clinical neurological
      examination as well as laboratory and imaging findings have to be added and
      categorized by a multilevel composition to establish a conclusive diagnosis.
      Simultaneously therapeutic measures for suspected primary cerebral diseases must
      be initiated, for example a rapid antibiotic treatment in case of a possible
      bacterial meningitis. A fast and structured diagnostic approach is crucial for
      ensuring a good prognosis and helps to miss relevant diagnostic steps. Potential
      diagnostic and therapeutic pitfalls must be kept in mind.

PMID- 22644494
TI  - [Prevention of psychic disorders].
AB  - Prevention aims to avoid the occurrence of psychiatric illness and disability
      caused by psychic disorders. The relevant interventions refer to the individual,
      the family context and other environmental factors. Universal and primary
      prevention target the entire population or a part of this (i. e. students).
      Secondary and selective intervention should prevent the manifestation of
      psychiatric disorders in vulnerable individuals (i. e. children with behavioral
      problems). Tertiary measures aim at preventing the worsening or recurrence of
      symptoms in individuals who already suffer from mental illness. Within the past
      25 years protective and risk factors that reduce or increase the probability of
      occurrence of mental disorders have increasingly been identified. This results in
      improved prevention. The present article gives an overview of preventive measures
      against the most common mental disorders in the light of the current evidence
      base.

PMID- 22644495
TI  - [Paradigm shift of German medicine by introduction of nurse practicioners. Does
      it make sense in view of experience in the United Kingdom?].
AB  - Germany wants to introduce some models to allow nurses to work in medical roles.
      Although hospital nurses worked hard during the last couple of years to
      concentrate on pure patient care and to detach themselves from medicine, a short
      additional training of 6-12 months duration is planned to allow them to work
      independently in well defined areas of medicine (high blood pressure, wound care,
      dementia, diabetes). However, success of such models has only been tested in a
      few studies. Study results and experience with such models in the UK - where
      these developments are much more advanced - are not only positive. Generally,
      work of nurses in medical roles does not make patient care less expensive and
      doctor's work less onerous. The benefit lies more in an add-on effect to doctor's
      care. Therefore, a close scientific surveillance of such models must be
      guaranteed and results must be considered without any kind of ideology.

PMID- 22644496
TI  - [AMNOG: Importance of the identification of target parameters for evidence of
      clinical effectiveness of innovative drugs].

PMID- 22644498
TI  - Precipitation-driven self-sorting of imines.
AB  - Judicious choice of precipitation conditions can lead to self-sorting of
      equilibrating mixtures of aromatic aldehydes and substituted anilines into a
      handful of imine products. The selectivity of this process is caused by the
      solubility differences among possible imines in the EtOH-H(2)O solvent mixtures
      used in precipitation.

PMID- 22644500
TI  - Orientation and conformation of lipids in crystals of transmembrane proteins.
AB  - Orientational order parameters and individual dihedral torsion angles are
      evaluated for phospholipid and glycolipid molecules that are resolved in X-ray
      structures of integral transmembrane proteins in crystals. The order parameters
      of the lipid chains and glycerol backbones in protein crystals are characterised
      by a much wider distribution of orientational order than is found in fluid lipid
      bilayers and reconstituted lipid-protein membranes. This indicates that the
      lipids that are resolved in crystals of membrane proteins are mostly not
      representative of the entire lipid-protein interface. Much of the chain
      configurational disorder of the membrane-bound lipids in crystals arises from C-C
      bonds in energetically disallowed skew conformations. This suggests
      configurational heterogeneity of the lipids at a single binding site: eclipsed
      conformations occur also in the glycerol backbone torsion angles and the C-C
      torsion angles of the lipid head groups. Conformations of the lipid glycerol
      backbone in protein crystals are not restricted to the gauche C1-C2 rotamers
      found invariably in phospholipid bilayer crystals. Lipid head-group conformations
      in the protein crystals also do not conform solely to the bent-down conformation,
      with gauche-gauche configuration of the phosphodiester, that is characteristic of
      phospholipid bilayer membranes. Stereochemical violations in the protein-bound
      lipids are evidenced by ester carboxyl groups in non-planar configurations, and
      even in the cis configuration. Some lipids have the incorrect enantiomeric
      configuration of the glycerol backbone, and many of the branched methyl groups in
      the phytanyl chains associated with bacteriorhodopsin have the incorrect S
      configuration.

PMID- 22644501
TI  - NMR q-space analysis of canonical shapes of human erythrocytes: stomatocytes,
      discocytes, spherocytes and echinocytes.
AB  - q-Space plots obtained experimentally using pulsed field-gradient stimulated echo
      (PGSTE) nuclear magnetic resonance (NMR) spectroscopy from water diffusing in red
      blood cells (RBCs) of different canonical (distinct variant) morphologies have
      "signature" features. The experimental q-space plots from suspensions of
      stomatocytes, echinocytes and spherocytes generated chemically had no diffraction
      features; in contrast a sample of blood from a patient with hereditary
      spherocytosis showed diffraction minima. To understand the forms of q-space
      plots, mathematical/geometrical models of discocytes, stomatocytes, echinocytes
      and spherocytes were used as restricting boundaries in simulations of water
      diffusion with Monte Carlo random walks. These simulations indicated that
      diffusion-diffraction minima are expected for each of the cell shapes considered.
      The absence of diffusion-diffraction minima in stomatocytes generated by
      dithiothreitol treatment was surmised to be due to non-alignment of the cells
      with the magnetic field of the NMR spectrometer. Differential interference
      contrast microscopy images of the chemically generated spherocyte and echinocyte
      suspensions showed them to be heterogeneous in cell shape. Therefore, we
      concluded that the shape heterogeneity caused the loss of the diffusion
      diffraction features, which were observed in the more homogeneous sample from a
      patient with hereditary spherocytosis, and in the simulations of homogeneous cell
      suspensions. This understanding of factors that affect q-space plots from RBC
      suspensions will assist morphological studies of other cell and tissue types.

PMID- 22644502
TI  - Straight lines of neutron scattering in biology: a review of basic controls in
      SANS and EINS.
AB  - Neutron and X-ray beams in scattering experiments have similar wavelengths and
      explore the same length scale (~1 A or 0.1 nm). Data collection and analysis are
      also broadly similar for both radiation types. There are fundamental differences,
      however, between the interaction of X-rays and neutrons with matter, which makes
      them strongly complementary for structural studies in biology. The property of
      neutrons to distinguish natural abundance hydrogen from its deuterium isotope and
      the dispersion relation that leads to the energy of ~1 A neutrons being of the
      order of thermal energy are well known. They form the basis, respectively, of
      contrast variation on the one hand and energy-resolved scattering experiments to
      study macromolecular dynamics-neutron-specific scattering methods on the other.
      Interestingly, analysis procedures for the structural and dynamics experiments
      display common aspects that can be expressed as straight-line relationships.
      These not only act as controls of good sample preparation, but also yield model
      free parameters on an absolute scale that provide fundamental information on the
      structure and dynamics of the system under study.

PMID- 22644503
TI  - Analysis and critical review of the development of bioethics in Belarus.
AB  - The main trends of the bioethics development in Belarus have been analyzed on the
      basis of the materials collected by the Ethics Documentation Center (ISEU, Minsk,
      Belarus). A critical review of the most important publications in the field since
      2000 suggests that development of bioethics in Belarus has occurred in two
      parallel directions distantly connected to each other: a theoretical direction
      and a practical one. Despite there are objective and subjective reasons for
      introducing bioethics in Belarus as an institutionally-organized system based on
      liberal values such as individual rights and freedom, a range of essential
      problems could be identified. Non-equivalent regulation of ethical issues in
      health care and other fields of biomedical research has been emphasized, as well
      as the problem of unclear hierarchical relationships among institutions dealing
      with various aspects of bioethics in the country and low ethical and educational
      level of the social and professional groups involved in further expansion of
      bioethical knowledge. The contextual aspects of the development of bioethics in
      the country such as the consequences of the Chernobyl disaster, the prevalence of
      the authoritarian social morality and traditionally paternalistic nature of the
      relations between physicians and their patients are discussed.

PMID- 22644504
TI  - Dating mattersTM: the next generation of teen dating violence prevention.

PMID- 22644505
TI  - Clip ligation of unruptured intracranial aneurysms: a prospective midterm outcome
      study.
AB  - BACKGROUND: We conducted a prospective study to investigate the clinical and
      radiological outcome in a surgical case series of 176 patients with 203
      unruptured intracranial aneurysms (UIA). METHODS: The success of aneurysm
      obliteration was assessed within 2 weeks after surgery by digital subtraction
      angiography (DSA). Patients also underwent angiography 5 years after surgery.
      Clinical outcomes were assessed using the modified Rankin Scale (mRS). All
      predictors of poor surgical outcomes were assessed using an exact logistic
      regression. RESULTS: Overall, 83 % of the patients had a good outcome (mRS score
      0 or 1); 10.8 % of the patients had a slight disability (mRS score 2), and 6.2 %
      of the patients had a moderate or moderate-severe disability (mRS score 3 or 4).
      The mortality rate was 0 % overall. The most important predictors of outcome were
      presence of history of ischemic cerebrovascular disease and postoperative stroke.
      Complete aneurysm occlusion was achieved in 93.5 % of all aneurysms. Sixty
      percent of treated aneurysms were checked with late follow-up DSA. No cases of
      hemorrhage from a surgically obliterated UIA were documented in this series
      during the 7.3 +/- 1.4 (SD)-year follow-up period. CONCLUSIONS: If patients are
      carefully selected and individually assigned to their optimum treatment modality,
      IUAs can be obliterated by surgery with a low percentage of unfavorable outcomes.

PMID- 22644506
TI  - Efficacy of adjuvant chemotherapy after surgery when considered over all cancer
      types: a synthesis of meta-analyses.
AB  - BACKGROUND: Despite a large number of clinical trials having been conducted to
      assess the efficacy of adjuvant chemotherapy after surgery for various cancers,
      whether it is best to use this treatment remains a generally contentious issue
      for many common cancers. The purpose of this study was to ascertain whether any
      general conclusions can be drawn about the efficacy or inefficacy of this
      treatment within different cancer classifications. METHODS: Meta-analyses of
      randomized, controlled trials (RCTs) of adjuvant chemotherapy after surgery were
      synthesized over as many types of cancer as possible. Data sources were Medline,
      Embase, and the Cochrane library. Eligible meta-analyses were meta-analyses of
      RCTs for any type of cancer that compared surgery followed by adjuvant
      chemotherapy with surgery followed by no adjuvant chemotherapy. RESULTS: The
      literature search found 25 meta-analyses for 15 cancer types that satisfied the
      criteria necessary for detailed analysis within this study. The estimates of
      relative risk for all cause mortality were reported as being less than one
      (indicating adjuvant chemotherapy is beneficial) by all meta-analyses apart from
      a meta-analysis for colorectal cancer metastasized to the liver. Moreover, 15 of
      these meta-analyses also reported that the 95% confidence interval for this
      relative risk is less than one (indicating statistical significance at the 5%
      level). CONCLUSIONS: The results for all cancer types included in this study
      except for cancer metastasized to the liver can be thought of as supporting each
      other through the idea of there being a common treatment effect or at least a
      common range of effect across all (or most) of these cancer types. For example,
      with regard to cancer types where the evidence in favor of adjuvant chemotherapy
      after surgery is only moderately strong, the results of this study may encourage
      more clinicians to regard the use of this treatment as standard practice.

PMID- 22644507
TI  - Systematic pelvic and aortic lymphadenectomy in advanced ovarian cancer patients
      at the time of interval debulking surgery: a double-institution case-control
      study.
AB  - BACKGROUND: The prognostic role of systematic lymphadenectomy remains unclear in
      advanced ovarian cancer (AOC). Only few retrospective case series have
      investigated the percentage of lymph node metastases after neoadjuvant
      chemotherapy. This multi-institutional case-control study analyzed the prognostic
      role of systematic lymphadenectomy in AOC patients at the time of interval
      debulking surgery (IDS). METHODS: From January 2005 to December 2010, the records
      of patients with AOC admitted to IDS at the Catholic University of Rome (n = 101,
      controls) and at the University of Bologna (n = 50, cases) were retrospectively
      analyzed. The cases, routinely submitted to systematic pelvic and aortic
      lymphadenectomy, were matched 1:2 with the controls, who did not routinely
      undergo lymphadenectomy. To correctly assess the prognostic role of
      lymphadenectomy, only patients with optimally debulked disease were included.
      Progression-free survival and overall survival were analyzed by a log-rank test.
      RESULTS: After an overall mean follow-up of 36 months (95% confidence interval 33
      39), 35 and 63 recurrences (70.0 vs. 62.4%; p = NS) and 15 and 24 deaths due to
      disease (30 vs. 23.7%; p = NS) were observed in the case and controls,
      respectively. The 2-year progression-free survival rate was 36 versus 25% (p =
      0.834), and the 2-year overall survival rate was 69 versus 88% (p = 0.777), in
      the case and controls, respectively. The median operating time was longer, and
      the percentage of patients requiring blood transfusions was higher in the cases
      than in the controls (225 vs. 210 min, p = 0.023, and 54 vs. 22.8%, p = 0.0001,
      respectively). CONCLUSIONS: Lymphadenectomy at the time of IDS could be omitted,
      at least in high-risk patients.

PMID- 22644508
TI  - Comparison of laparoscopic-assisted radical vaginal hysterectomy and laparoscopic
      radical hysterectomy in the treatment of cervical cancer.
AB  - BACKGROUND: The aim of this study was to compare the surgical and oncologic
      outcomes of laparoscopic-assisted radical vaginal hysterectomy (LARVH) with that
      of laparoscopic radical hysterectomy (LRH) for early-stage cervical cancer.
      METHODS: Patients affected by invasive cervical cancer (FIGO stage I-IIA) who had
      received LARVH (n = 89) in our institute between September 2004 and December 2010
      were compared with patients treated by LRH (n = 105) during the same period. All
      patient information, surgical and pathological data, and oncological results were
      prospectively collected. Patients undergoing abdominal radical hysterectomy (ARH)
      were included for comparison of safety, morbidity, and recurrence rate. RESULTS:
      The mean estimated blood loss (EBL) and return of bowel activity were
      significantly reduced in the LRH group compared with the LARVH group (p = .011
      and p = .002, respectively). Intraoperative complications occurred in 10 patients
      (11.2 %) in the LARVH group, 6 (5.7 %) in the LRH group, and 3 (3.0 %) in the ARH
      group. Forest plot analyses of the previous studies showed higher incidence of
      intraoperative complication in the LARVH group than in LRH group (p = .02).
      Despite the similar overall recurrence rate, stump recurrence seems to be high in
      the LRH group in the forest plot analysis of previous studies (p = 0.08).
      CONCLUSIONS: Both LARVH and LRH are safe and effective therapeutic procedures for
      the management of early-stage cervical cancer, although LRH is characterized by
      less blood loss and shorter bowel recovery time. Possible higher stump recurrence
      in the LRH should be further evaluated.

PMID- 22644509
TI  - Robotic transperitoneal aortic lymphadenectomy in gynecologic cancer: a new
      robotic surgical technique and review of the literature.
AB  - BACKGROUND: Lymph node status is a prognostic factor for gynecologic cancer. We
      describe a new developing strategy for robotic transperitoneal aortic
      lymphadenectomy without relocating the robotic column or the patient. METHODS:
      Patients with histologically confirmed cervical cancer, early ovarian cancer, or
      endometrial carcinoma with suspected risk factors indicating aortic
      lymphadenectomy were eligible for the robotic transperitoneal aortic
      lymphadenectomy using the Da Vinci robotic system as part of the surgical
      treatment of gynecologic malignancies. RESULTS: The mean operating time was 224
      min (range 160-300 min), and the mean console time for aortic lymphadenectomy was
      43 min (range 30-75). The median hemoglobin fall was 1.3 g/dL range (0.8-2 g/dL),
      the median number of removed aortic lymph nodes was 12.5 (range 7-17), and the
      median length of the hospital stay was 2 days (range 1-4 days). We experienced an
      intraoperative complication, but no conversion to laparotomy was necessary. No
      patients received a blood transfusion. CONCLUSIONS: This initial experience
      demonstrates the feasibility of robotic aortic lymphadenectomy with good accuracy
      and safety without relocating the robotic column or the patient.

PMID- 22644510
TI  - Twenty-year outcomes after breast-conserving surgery and definitive radiotherapy
      for mammographically detected ductal carcinoma in situ.
AB  - BACKGROUND: Management of mammographically detected ductal carcinoma in situ
      (DCIS) at a single institution was reviewed to determine long-term clinical
      outcomes after treatment with breast-conserving therapy (BCT). METHODS: Data from
      all patient-cases with DCIS who received BCT between 1980 and 1993 were reviewed.
      Patient demographics and pathologic factors were analyzed for their effect on
      outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival. BCT
      included breast-conserving surgery followed by external-beam radiotherapy to the
      whole breast, with 86 % of patients receiving a lumpectomy cavity boost. The
      median dose to the whole breast was 50 Gy and 60.4 Gy to the lumpectomy cavity.
      RESULTS: A total of 129 cases were evaluated; the median follow-up was 19.3
      years. Twenty-one patients developed an ipsilateral breast tumor recurrence
      (IBTR), 76.2 % of which were invasive (n = 16). Fourteen recurrences (66 %) were
      within the same breast quadrant (true recurrence), while an additional 7 cases
      developed an IBTR elsewhere in the breast. True recurrences were more prevalent
      in women <45 years of age (20 %/24 % vs. 5.1 %/8 %) at 10 and 20 years (p =
      0.02). The 5-, 10-, 15-, and 20-year actuarial rates of IBTR for this cohort were
      8.7, 10.4, 12.1, and 16.3 % (IBTR), while overall survival at 5, 10, and 20 years
      was 97.6, 96.8, and 96.8 %, respectively. CONCLUSIONS: Mammographically detected
      DCIS remains a clinically distinct subset of noninvasive breast cancer. With 20
      year follow-up, local control and overall survival are excellent after BCT.

PMID- 22644511
TI  - FDG-PET SUVmax combined with IASLC/ATS/ERS histologic classification improves the
      prognostic stratification of patients with stage I lung adenocarcinoma.
AB  - BACKGROUND: We investigated the association between the newly proposed
      International Association for the Study of Lung Cancer (IASLC)/American Thoracic
      Society (ATS)/European Respiratory Society (ERS) classification and (18)F
      fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET), and
      whether the combination of these radiologic and pathologic factors can further
      prognostically stratify patients with stage I lung adenocarcinoma. METHODS: We
      retrospectively evaluated 222 patients with pathologic stage I lung
      adenocarcinoma who underwent FDG-PET scanning before undergoing surgical
      resection between 1999 and 2005. Patients were classified by histologic grade
      according to the IASLC/ATS/ERS classification (low, intermediate, or high grade)
      and by maximum standard uptake value (SUVmax) (low <3.0, high >=3.0). The
      cumulative incidence of recurrence (CIR) was used to estimate recurrence
      probabilities. RESULTS: Patients with high-grade histology had higher risk of
      recurrence (5-year CIR, 29% [n = 25]) than those with intermediate-grade (13% [n
      = 181]) or low-grade (11% [n = 16]) histology (p = 0.046). High SUVmax was
      associated with high-grade histology (p < 0.001) and with increased risk of
      recurrence compared to low SUVmax (5-year CIR, 21% [n = 113] vs. 8% [n = 109]; p
      = 0.013). Among patients with intermediate-grade histology, those with high
      SUVmax had higher risk of recurrence than those with low SUVmax (5-year CIR, 19%
      [n = 87] vs. 7% [n = 94]; p = 0.033). SUVmax was associated with recurrence even
      after adjusting for pathologic stage (p = 0.037). CONCLUSIONS: SUVmax on FDG-PET
      correlates with the IASLC/ATS/ERS classification and can be used to stratify
      patients with intermediate-grade histology, the predominant histologic subtype,
      into two prognostic subsets.

PMID- 22644512
TI  - Is serum alpha-fetoprotein useful for predicting recurrence and mortality
      specific to hepatocellular carcinoma after hepatectomy? A test based on
      propensity scores and competing risks analysis.
AB  - BACKGROUND: Serum alpha-fetoprotein (AFP) is frequently used to predict
      posthepatectomy outcomes in patients with hepatocellular carcinoma (HCC), but its
      predictive value is still not established. Therefore, we assessed the prognostic
      significance of AFP status. METHODS: Of 525 patients undergoing curative
      hepatectomy for HCC, 290 had preoperative AFP levels of >=20 ng/mL (AFP-positive
      group) and 235 had AFP levels of <20 ng/mL (AFP-negative group). We compared the
      2 groups with respect to time-to-recurrence, using the inverse probability of
      treatment weighted (IPTW) for the entire cohort and propensity score matching,
      and the cumulative incidence of HCC-specific mortality using competing risks
      regression. RESULTS: During follow-up (median duration 64 months, range 2-137
      months), HCC recurred in 54.9 % of the AFP-negative group and 52.4 % of the AFP
      positive group; there was no death without recurrence. After IPTW adjustment,
      time-to-recurrence did not differ in the 2 groups (hazard ratio [HR] 0.86, 95 %
      confidence interval [95 % CI] 0.66-1.12; P = 0.28). In a propensity-score matched
      cohort (152 pairs), time-to-recurrence data were similar to those obtained by
      IPTW adjustment (HR 0.91, 95 % CI 0.65-1.25; P = 0.55). There was no difference
      in recurrence pattern (site and stage) or treatment between the 2 groups even
      after propensity-score matching. The adjusted HR evaluating the impact of AFP
      positivity on the risk of HCC-specific mortality was 0.77 (95 % CI 0.54-1.08; P =
      0.13) A multivariable competing risks analysis also failed to reveal a
      significant correlation between baseline AFP level and HCC-specific mortality in
      the AFP-positive group. CONCLUSIONS: Preoperative AFP levels are not useful for
      predicting recurrence or survival endpoints following curative hepatectomy for
      HCC.

PMID- 22644513
TI  - Systematic review of sentinel lymph node mapping procedure in colorectal cancer.
AB  - BACKGROUND: The clinical impact of sentinel lymph node (SN) biopsy in colorectal
      cancer is still controversial. The aim of our study was to determine the accuracy
      of this procedure from published data and to identify factors that contribute to
      the conflicting reports. METHODS: A systematic search of the Medline, Embase, and
      Cochrane databases up to July 2011 revealed 98 potentially eligible studies, of
      which 57 were analyzed including 3,934 patients (3,944 specimens). RESULTS: The
      pooled SN identification rate was 90.7% (95% CI 88.2-93.3), with a significant
      higher identification rate in studies including more than 100 patients or studies
      using the ex vivo SN technique. The pooled sensitivity of the SN procedure was
      69.6% (95% CI 64.7-74.6). Including the immunohistochemical findings increased
      the pooled sensitivity of SN procedure to 80.2% (95% CI 4.7-10.7). Subgroups with
      significantly higher sensitivity could be identified: >=4 SNs versus <4 SNs (85.2
      vs. 66.3%, p = 0.003), colon versus rectal cancer (77.6 vs. 65.7%, p = 0.04),
      early T1 or T2 versus advanced T3 or T4 carcinomas (93.4 vs. 58.8%, p = 0.01).
      Serial sectioning and immunohistochemistry resulted in a mean upstaging of 18.9%
      (range 0-50%). True upstaging defined as micrometastases (pN1mi+) rather than
      isolated tumor cells (pN0itc+) was 7.7%. CONCLUSIONS: The SN procedure in
      colorectal cancer has an overall sensitivity of 70%, with increased sensitivity
      and refined staging in early-stage colon cancer. Because the ex vivo SN mapping
      is an easy technique it should be considered in addition to conventional
      resection in colon cancer.

PMID- 22644514
TI  - Expression of mesenchymal markers vimentin and fibronectin: the clinical
      significance in esophageal squamous cell carcinoma.
AB  - BACKGROUND: The importance of mesenchymal characteristics has not been fully
      elucidated in esophageal cancer. METHODS: Ten normal and 77 tumor specimens were
      collected. Microarray analysis was performed to analyze the expression patterns
      of epithelial markers, mesenchymal markers, epithelial mesenchymal transition
      (EMT)-related genes and stem cell markers. RT-PCR analysis was conducted to
      confirm the results of microarray analysis. Immunohistochemical analysis was
      performed to verify the level of protein expression. Statistical analysis was
      performed to investigate the correlation between selected genes and
      clinicopathological factors. RESULTS: Microarray analysis showed that epithelial
      markers were significantly down-regulated whereas mesenchymal markers and EMT
      transcription factors were up-regulated in cancer cells. Two types of gene
      expression patterns were found in the clustering analysis, type 1 tumors and type
      2 tumors. Type 1 tumor clusters did not reveal a fixed gene expression pattern
      whereas type 2 tumor clusters revealed up-regulation of mesenchymal markers EMT
      inducers and related genes. Vimentin and fibronectin were selected to distinguish
      between tumor types 1 and 2. Type 2 tumors showed significantly larger tumor
      sizes (p < 0.0001), wider ranges of lymph node metastasis (p = 0.0057), and a
      more severe clinical stage (p < 0.0001) than did type 1 tumors. The prognosis of
      patients with type 2 tumors was significantly worse than that of patients with
      type 1 tumors. Univariate and multivariate analyses revealed that classification
      of type 2 tumors was an independent prognostic factor. CONCLUSIONS: The analysis
      of mesenchymal markers in esophageal cancer is useful in distinguishing patients
      with a poor prognosis.

PMID- 22644515
TI  - CCR7 and VEGF-C: molecular indicator of lymphatic metastatic recurrence in pN0
      esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy?
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with a
      high incidence of lymph node metastasis. This study was undertaken to investigate
      the expression of CCR7 and VEGF-C in pN0 ESCC and its relationship with lymphatic
      metastatic recurrence. METHODS: The expression of CCR7 and VEGF-C was examined by
      RT-PCR and immunohistochemistry. The recurrence rates were calculated by the
      Kaplan-Meier method and their difference was determined by log rank analysis. Cox
      regression analysis was performed to determine the independent risk factors.
      RESULTS: In 99 patients, CCR7 mRNA expression was observed in 42 patients with a
      3 year recurrence rate of 57.1%; VEGF-C mRNA expression was observed in 52
      patients with a 3 year recurrence rate of 53.8%; and coexpression of CCR7 mRNA
      and VEGF-C mRNA was observed in 22 patients with a 3 year recurrence of 63.6%.
      Neither CCR7 mRNA nor VEGF-C mRNA expression was observed in 27 patients with a 3
      year recurrence rate of 22.2%. The recurrence rates of patients with positive
      expression of CCR7 mRNA and/or VEGF-C mRNA were significantly higher than in
      patients without expression of both CCR7 mRNA and VEGF-C mRNA. We achieved better
      concordance between RT-PCR and immunohistochemistry detection of both markers.
      The Cox regression analysis showed tumor T classification, positive expression of
      CCR7/VEGF-C mRNA, and positive expression of CCR7/VEGF-C protein in tumor tissues
      to be independent risk factors for 3 year recurrence. CONCLUSIONS: Patients with
      positive expression of CCR7 and/or VEGF-C have a higher recurrence rate than
      patients without expression of both CCR7 and VEGF-C. CCR7 and VEGF-C may become
      molecular indicators of disease in patients vulnerable to lymphatic metastatic
      recurrence.

PMID- 22644516
TI  - Robot-assisted Supraomohyoid neck dissection via a modified face-lift or
      retroauricular approach in early-stage cN0 squamous cell carcinoma of the oral
      cavity: a comparative study with conventional technique.
AB  - BACKGROUND: Supraomohyoid neck dissection (SOND) in clinical N0 (cN0) neck of
      oral cavity squamous cell carcinoma (SCC) is performed by many head and neck
      surgeons showing improved regional control and disease-specific survival.
      However, disfiguring neck scars have been accepted to be unavoidable. In this
      study, we sought to introduce and evaluate the feasibility of our surgical
      technique to hide the external scar of neck dissection using the robotic system
      via a modified face-lift or retroauricular approach. METHODS: Twenty-six patients
      with cN0 oral cavity SCC were divided into two groups of robot-assisted neck
      dissection and conventional neck dissection via external cervical incision. The
      operation time, amount and duration of drainage, length of hospital stay,
      complications, number of retrieved lymph nodes, and satisfaction scores were
      compared. RESULTS: Mean operation time was longer in the robot-assisted group
      (157 +/- 22 min) than the conventional group (78 +/- 16 min) (P < 0.001).
      However, the amount and duration of drainage, hospital stay, retrieved lymph
      nodes, and complications were comparable. Because the postoperative scar was
      hidden by the auricle and hair, the satisfaction score was significantly higher
      in the robot-assisted group (P < 0.001). CONCLUSIONS: Robot-assisted SOND via a
      modified face-lift or retroauricular approach in cN0 oral cavity SCC was feasible
      compared to conventional technique and showed a clear cosmetic benefit. Longer
      operation time remains the drawback of this procedure. However, it could be
      considered for patients who require SOND and prefer to avoid external neck scar.

PMID- 22644517
TI  - Evaluation of incomplete sentinel node biopsy procedures and sentinel node
      positivity rates as surgical quality-assurance parameters in melanoma patients.
AB  - BACKGROUND: There is little literature describing quality assurance (QA)
      validation of an individual surgeon's ability to perform sentinel node biopsy
      (SNB) in melanoma patients. This study aims to evaluate incomplete SNB rates and
      SNB positivity rates as potential QA parameters. METHODS: An institutional
      database identified 2,874 patients with primary melanoma who had SNB performed
      when there was lymphoscintigraphy drainage to a single lymphatic field.
      Lymphoscintigraphy data were obtained from another database. Lymphoscintigraphy
      utilized small-particle colloid, allowing visualization of channels entering
      sentinel nodes on early dynamic scanning. Incomplete SNB was defined as retrieval
      of fewer sentinel nodes than identified on lymphoscintigraphy. RESULTS: The
      overall rate of incomplete SNB was 17.7 % (including axilla 7.8 %, neck 23.3 %,
      and groin 28.8 %). Individual surgeons varied significantly in their proportion
      of SNBs performed in each region (p < 0.001). The surgeons' overall incomplete
      SNB rate varied significantly (p < 0.001). The surgeons' incomplete SNB rate in
      the axilla ranged 3-16 % (p < 0.001), median 6 %; groin 21-41 % (p = 0.002),
      median 26 %; and neck 19-43 % (p = 0.374), median 22 %. The respective axillary,
      groin, and neck SNB positivity rate for incomplete SNB patients were 10, 23, and
      18 % compared to "complete" SNB patients 14, 19, and 14 %. There were no
      significant differences between surgeons' SNB positivity rates. CONCLUSIONS:
      Incomplete SNB rates vary between surgeons in each region. SNB positivity rates
      do not vary commensurate with the incomplete SNB rates. The ranges described
      could be used as QA parameters, however because none of these experienced
      surgeons are outliers, the robustness of these parameters remains unproven.

PMID- 22644518
TI  - [Frontotemporal dementia and amyotrophic lateral sclerosis--two ends of the same
      phenotypical spectrum].

PMID- 22644519
TI  - [Innovations in neuro-monitoring using transcranial ultrasound].
AB  - This review describes transcranial ultrasound-based neuromonitoring by assessing
      changes of brain structures or cerebral blood flow over time. Some of the
      presented ultrasound techniques are still experimental. They are advantageous as
      they provide non-invasive and bed-side imaging. Thus, time, costs and potentially
      hazardous side effects due to transportation of acutely ill patients to CT or MRI
      scanners can be avoided. An assessment of increased cerebral pressure can be
      achieved by repeated determination of individual pulsatility index, cerebral
      venous blood flow, midline shift and transorbital optic sheath measurements.
      Moreover, transcranial duplex sonography offers the possibility to detect
      intracranial haemorrhage and to guide neurosurgical interventions. Finally, the
      value of measuring cerebral autoregulation and the current state of the art
      regarding sonothrombolysis in acute intracranial arterial thrombosis is
      presented.

PMID- 22644521
TI  - [Compulsive buying].

PMID- 22644520
TI  - [Inclusion body myositis, Paget's disease of the bone and frontotemporal
      dementia: early involvement of the heart and respiratory muscles].
AB  - Since valosin-containing protein mutations were reported as a cause of hereditary
      inclusion body myositis associated with Paget's disease of the bone and
      frontotemporal dementia, many new mutations have been described in the last
      decade. We report on a 46-year-old German male with a progressive tetraparesis
      and autosomal dominant inheritance pattern. Echocardiography revealed a beginning
      dilated cardiomyopathy and laboratory analyses showed increased alkaline
      phosphatase. Decreased verbal memory and an impairment of concept building were
      observed on neuropsychological examination. Muscle biopsy demonstrated a
      myopathic pattern, rimmed vacuoles, CD8+ T-cell infiltrates and positive MHC1
      muscle fibres. We found a heterozygote mutation in exon 5 of the valosin
      containing protein gene (c.464G > T p.Arg155Leu), which until now has been
      described only in an Australian family. We describe here the first German case
      with the above-mentioned mutation causing inclusion-body myositis associated with
      Paget's disease of the bone and fronto-temporal dementia. Here, we recommend
      regular controls of cardiac and respiratory functions.

PMID- 22644522
TI  - Exploring the allosteric mechanism of dihydrodipicolinate synthase by reverse
      engineering of the allosteric inhibitor binding sites and its application for
      lysine production.
AB  - Dihydrodipicolinate synthase (DHDPS, EC 4.2.1.52) catalyzes the first committed
      reaction of L-lysine biosynthesis in bacteria and plants and is allosterically
      regulated by L-lysine. In previous studies, DHDPSs from different species were
      proved to have different sensitivity to L-lysine inhibition. In this study, we
      investigated the key determinants of feedback regulation between two industrially
      important DHDPSs, the L-lysine-sensitive DHDPS from Escherichia coli and L-lysine
      insensitive DHDPS from Corynebacterium glutamicum, by sequence and structure
      comparisons and site-directed mutation. Feedback inhibition of E. coli DHDPS was
      successfully alleviated after substitution of the residues around the inhibitor's
      binding sites with those of C. glutamicum DHDPS. Interestingly, mutagenesis of
      the lysine binding sites of C. glutamicum DHDPS according to E. coli DHDPS did
      not recover the expected feedback inhibition but an activation of DHDPS by L
      lysine, probably due to differences in the allosteic signal transduction in the
      DHDPS of these two organisms. Overexpression of L-lysine-insensitive E. coli
      DHDPS mutants in E. coli MG1655 resulted in an improvement of L-lysine production
      yield by 46 %.

PMID- 22644523
TI  - An advanced PCR method for the specific detection of viable total coliform
      bacteria in pasteurized milk.
AB  - Pasteurized milk is a complex food that contains various inhibitors of polymerase
      chain reaction (PCR) and may contain a large number of dead bacteria, depending
      on the milking conditions and environment. Ethidium monoazide bromide (EMA)-PCR
      is occasionally used to distinguish between viable and dead bacteria in foods
      other than pasteurized milk. EMA is a DNA-intercalating dye that selectively
      permeates the compromised cell membranes of dead bacteria and cleaves DNA.
      Usually, EMA-PCR techniques reduce the detection of dead bacteria by up to 3.5
      logs compared with techniques that do not use EMA. However, this difference may
      still be insufficient to suppress the amplification of DNA from dead Gram
      negative bacteria (e.g., total coliform bacteria) if they are present in
      pasteurized milk in large numbers. Thus, false positives may result. We developed
      a new method that uses real-time PCR targeting of a long DNA template (16S-23S
      rRNA gene, principally 2,451 bp) following EMA treatment to completely suppress
      the amplification of DNA of up to 7 logs (10(7) cells) of dead total coliforms.
      Furthermore, we found that a low dose of proteinase K (25 U/ml) removed PCR
      inhibitors and simultaneously increased the signal from viable coliform bacteria.
      In conclusion, our simple protocol specifically detects viable total coliforms in
      pasteurized milk at an initial count of >=1 colony forming unit (CFU)/2.22 ml
      within 7.5 h of total testing time. This detection limit for viable cells
      complies with the requirements for the analysis of total coliforms in pasteurized
      milk set by the Japanese Sanitation Act (which specifies <1 CFU/2.22 ml).

PMID- 22644524
TI  - Cloning, sequencing, and characterization of lipase genes from a
      polyhydroxyalkanoate (PHA)-synthesizing Pseudomonas resinovorans.
AB  - Lipase (lip) and lipase-specific foldase (lif) genes of a biodegradable
      polyhydroxyalkanoate (PHA)-synthesizing Pseudomonas resinovorans NRRL B-2649 were
      cloned using primers based on consensus sequences, followed by polymerase chain
      reaction-based genome walking. Sequence analyses showed a putative Lip gene
      product (314 amino acids, a.a.) with its catalytic active site (Ser(111),
      Asp(258), and His(280)) identified. The foldase lif gene that is located 55 bp
      downstream of lip codes for a putative Lif (345 a.a.). To verify the biological
      function of the cloned lip gene for lipase expression in P. resinovorans, we
      constructed a lip knock-out mutant (lip::Tn5<KAN-2>) by transposon insertion.
      Complementation of the lip knock-out P. resinovorans mutant with a lipase
      expression plasmid (pBS29-P2-lip) was performed, and its effect on lipase
      expression was investigated. The wild-type P. resinovorans and the lip::Tn5<KAN
      2>[pBS29-P2-lip] recombinant (but not the lip::Tn5<KAN-2> mutant) showed
      fluorescence on rhodamine B plates indicative of lipase activity. The wild type
      exhibited extracellular lipase activity when grown on medium containing
      triacylglycerol substrates (tallow, olive oil, and tributyrin) as sole carbon
      sources, but the lip::Tn5<KAN-2> mutant did not show such activity. Lipase
      activity of various strains was also confirmed by TLC analysis of the composition
      of acylglycerols and free fatty acid in the extracts of the spent culture medium.
      We further found that tributyrin was more effective than olive oil in inducing
      lipase expression in P. resinovorans.

PMID- 22644525
TI  - Efficient heterologous expression and secretion in Aspergillus oryzae of a llama
      variable heavy-chain antibody fragment V(HH) against EGFR.
AB  - We have constructed a filamentous fungus Aspergillus oryzae that secretes a llama
      variable heavy-chain antibody fragment (V(HH)) that binds specifically to
      epidermal growth factor receptor (EGFR) in a culture medium. A major improvement
      in yield was achieved by fusing the V(HH) with a Taka-amylase A signal sequence
      (sTAA) and a segment of 28 amino acids from the N-terminal region of Rhizopus
      oryzae lipase (N28). The yields of secreted, immunologically active anti-EGFR
      V(HH) reached 73.8 mg/1 in a Sakaguchi flask. The V(HH) fragments were released
      from the sTAA or N28 proteins by an indigenous A. oryzae protease during
      cultivation. The purified recombinant V(HH) fragment was specifically recognized
      and could bind to the EGFR with a high affinity.

PMID- 22644526
TI  - The stability of almond beta-glucosidase during combined high pressure-thermal
      processing: a kinetic study.
AB  - The thermal and the combined high pressure-thermal inactivation kinetics of
      almond beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) were
      investigated at pressures from 0.1 to 600 MPa and temperatures ranging from 30 to
      80  degrees C. Thermal treatments at temperatures higher than 50  degrees C
      resulted in significant inactivation with complete inactivation after 2 min of
      treatment at 80  degrees C. Both the thermal and high pressure inactivation
      kinetics were described well by first-order model. Application of pressure
      increased the inactivation kinetics of the enzyme except at moderate temperatures
      (50 to 70  degrees C) and pressures between 0.1 and 100 MPa where slight pressure
      stabilisation of the enzyme against thermal denaturation was observed. The
      activation energy for the inactivation of the enzyme at atmospheric pressure was
      estimated to be 216.2+/-8.6 kJ/mol decreasing to 55.2+/-3.9 kJ/mol at 600 MPa.
      The activation volumes were negative at all temperature conditions excluding the
      temperature-pressure range where slight pressure stabilisation was observed. The
      values of the activation volumes were estimated to be -29.6+/-0.6, -29.8+/-1.7, 
      20.6+/-3.2, -41.2+/-4.8, -36.5+/-1.8, -39.6+/-4.3, -31.0+/-4.5 and -33.8+/-3.9
      cm3/mol at 30, 35, 40, 45, 50, 60, 65 and 70  degrees C, respectively, with no
      clear trend with temperature. The pressure-temperature dependence of the
      inactivation rate constants was well described by an empirical third-order
      polynomial model.

PMID- 22644527
TI  - Recombinant production of mGLP-1 by coupling of refolding and intein-mediated
      self-cleavage (CRIS).
AB  - Glucagon-like peptide-1 as an endogenous glucose-lowering peptide is a promising
      candidate for anti-diabetic drug development. Here, we developed a convenient
      method by coupling of refolding and intein-mediated self-cleavage (CRIS) to
      improve the recombinant production of a mutated glucagon-like peptide-1 (mGLP-1).
      Bacterial cell culture employing auto-induction was performed at 37  degrees C to
      avoid the intracellular self-cleavage of the intein fusion protein. The impacts
      of urea, pH, and temperature on the efficiency of CRIS were tested, and then, the
      optimized CRIS was established. Using the optimized method, we obtained the
      purified mGLP-1 with a yield of 3.41 mg peptide/g bacterial cells which was 5.6
      fold higher than before. After that, using chromatography, peptide
      electrophoresis, and mass spectrometry, we determined the purity and molecular
      weight of the purified peptide and then confirmed its glucose-lowering activity
      by performing glucose tolerance test in mice. These results suggest that CRIS is
      a relatively simple and efficacious method for the recombinant production of mGLP
      1, and as a general method, it can also be used for the recombinant preparation
      of some other proteins and peptides.

PMID- 22644528
TI  - Genome mining and motif modifications of glycoside hydrolase family 1 members
      encoded by Geobacillus kaustophilus HTA426 provide thermostable 6-phospho-beta
      glycosidase and beta-fucosidase.
AB  - Members of glycoside hydrolase family 1 (GH1) hydrolyze various glycosides and
      are widely distributed in organisms. With the aim of producing thermostable GH1
      catalysts with potential applications in biotechnology, three GH1 members encoded
      by the thermophile Geobacillus kaustophilus HTA426 (GK1856, GK2337, and GK3214)
      were characterized using 24 p-nitrophenyl glycosides as substrates. GK1856 and
      GK3214 exhibited 6-phospho-beta-glycosidase activity, while GK2337 did not.
      GK3214 was extremely thermostable and retained most of its activity during 7 days
      of incubation at 60  degrees C. GK3214 was found to have transglycosylation
      activity, a dimeric structure, and a possible motif that governed its substrate
      specificity. Substitution of the GK3214 motif with that of a beta-glucosidase
      resulted in the unexpected generation of a thermostable, highly specific beta
      fucosidase, concomitant with large increases in beta-glucosidase, beta
      cellobiosidase, alpha-arabinofuranosidase, beta-mannosidase, beta-glucuronidase,
      beta-xylopyranosidase, and beta-fucosidase activities and a dramatic decline in 6
      phospho-beta-glycosidase activity. This is the first report to identify a gene
      encoding thermostable 6-phospho-beta-glycosidase and to generate a thermostable
      beta-fucosidase. These results provided thermostable enzyme catalysts and also
      suggested a promising approach to develop novel GH1 biocatalysts.

PMID- 22644529
TI  - Transcripts of a heterologous gene encoding mite allergen Der f 7 are stabilized
      by codon optimization in Aspergillus oryzae.
AB  - We have previously demonstrated that transcripts of an AT-biased heterologous
      gene encoding mite allergen Der f 7 from Dermatophagoides farinae were
      polyadenylated prematurely within the coding region when native cDNA was
      expressed in Aspergillus oryzae, and that this premature polyadenylation was
      prevented by the codon optimization of the Der f 7 gene, resulting in increased
      steady-state mRNA levels. In this study, we tested the stability of transcription
      products derived from expression constructs of the native and codon-optimized Der
      f 7 gene in A. oryzae using 1,10-phenanthroline as a transcription inhibitor.
      Transcription products of native Der f 7 cDNA fused to the A. oryzae glucoamylase
      gene (glaA) were rapidly degraded; the half-life of the mRNA was approximately 13
      min. However, the half-life of codon-optimized Der f 7 mRNA fused to glaA was
      approximately 43 min, which was highly similar to that of endogenous glaA mRNA.
      These results indicate that Der f 7 mRNA is significantly stabilized by codon
      optimization. In addition, Der f 7 mRNA was stabilized by the codon optimization
      of only the 3'-half region, where premature polyadenylation sites were
      exclusively situated; the half-life of the chimeric Der f 7 mRNA was
      approximately 39 min. This suggested that destabilization of native Der f 7 mRNA
      is mainly triggered by premature polyadenylation within the coding region. To the
      best of our knowledge, this is the first report to provide experimental evidence
      that heterologous mRNA is significantly stabilized by codon optimization in
      eukaryotic cells.

PMID- 22644530
TI  - Degradation of paracetamol by pure bacterial cultures and their microbial
      consortium.
AB  - Three bacterial strains utilizing paracetamol as the sole carbon, nitrogen, and
      energy source were isolated from a paracetamol-degrading aerobic aggregate, and
      assigned to species of the genera Stenotrophomonas and Pseudomonas. The
      Stenotrophomonas species have not included any known paracetamol degraders until
      now. In batch cultures, the organisms f1, f2, and fg-2 could perform complete
      degradation of paracetamol at concentrations of 400, 2,500, and 2,000 mg/L or
      below, respectively. A combination of three microbial strains resulted in
      significantly improved degradation and mineralization of paracetamol. The co
      culture was able to use paracetamol up to concentrations of 4,000 mg/L, and
      mineralized 87.1 % of the added paracetamol at the initial of 2,000 mg/L. Two key
      metabolites of the biodegradation pathway of paracetamol, 4-aminophenol, and
      hydroquinone were detected. Paracetamol was degraded predominantly via 4
      aminophenol to hydroquinone with subsequent ring fission, suggesting new pathways
      for paracetamol-degrading bacteria. The degradation of paracetamol could thus be
      performed by the single isolates, but is stimulated by a synergistic interaction
      of the three-member consortium, suggesting a possible complementary interaction
      among the various isolates. The exact roles of each of the strains in the
      consortium need to be further elucidated.

PMID- 22644531
TI  - On the evolution of one-electron-oxidized deoxyguanosine in damaged DNA under
      physiological conditions: a DFT and ONIOM study on proton transfer and
      equilibrium.
AB  - Different deprotonation paths of the radical cation formed by one-electron
      oxidation of 2'-deoxyguanosine (2dG) sites in DNA have been studied using Density
      Functional Theory (M05-2X/6-31+G(d,p)) and ONIOM methodology (M05-2X/6
      31+G(d,p):PM6) in conjunction with the SMD model to include the solvent effects.
      Models of increased complexity have been used ranging from the isolated
      nucleoside to a three unit double-stranded oligomer including the sugar units,
      the base pairing with cytidine, and the phosphate linkage. The reported results
      correspond to aqueous solution, at room temperature, and pH = 7.4. Under such
      conditions it was found that the proton transfer (PT) within the base pair is a
      minor path compared to the PT between the base pair and the surrounding water. It
      was also found that the deprotonation of ground-state 2dG(+) sites mainly yields
      C centered radicals in the sugar unit, with the largest populations corresponding
      to C4' and C5', followed by C3'. The different aspects of the presented
      theoretical study have been validated with experimental results.

PMID- 22644532
TI  - Elastic and viscoelastic characterization of mouse oocytes using micropipette
      indentation.
AB  - This paper reports the first quantitative comparison study of elastic and
      viscoelastic properties of oocytes from young and aged mice. A force measurement
      technique, including a poly(dimethylsiloxane) (PDMS) cell holding device and a
      sub-pixel computer vision tracking algorithm, is utilized for measuring forces
      applied to an oocyte and resultant cell deformations in real time during oocyte
      manipulation. To characterize elastic and viscoelastic properties of the oocytes,
      a stress-relaxation indentation test is performed. A two-step, large-deformation
      mechanical model is developed to extract the mechanical properties of the oocytes
      from the measured force-deformation data. The experimental results demonstrate
      that the aged oocytes are significantly softer (instantaneous modulus: 2.2 vs.
      5.2 kPa in young oocytes) but more viscous (relaxation time: 4.1 vs. 2.3 s in
      young oocytes) than the young oocytes.

PMID- 22644533
TI  - HIV infection, pulmonary arterial hypertension and pregnancy: a fatal triad.
AB  - A 30-year-old pregnant HIV-seropositive woman presented with symptoms and signs
      suggestive of severe pulmonary arterial hypertension, with a fatal outcome.
      Histological features of pulmonary arterial hypertension were present at post
      mortem. This is the first report of histologically confirmed HIV-associated
      pulmonary arterial hypertension associated with pregnancy in Africa.

PMID- 22644536
TI  - Stereotactic radiation therapy for progressive residual pilocytic astrocytomas.
AB  - This report shows the results of stereotactic radiation therapy for progressive
      residual pilocytic astrocytomas. Medical records of patients who had undergone
      stereotactic radiation therapy for a progressive residual pilocytic astrocytoma
      were reviewed. Between 1995 and 2010, 12 patients with progression of a residual
      pilocytic astrocytoma underwent stereotactic radiation therapy at UCLA.
      Presentation was headache (4), visual defects (3), hormonal disturbances (2),
      gelastic seizures (2) and ataxia (1). MRI showed a cystic (9), mixed solid/cystic
      (2) or solid tumor (1); located in the hypothalamus (5), midbrain (3), thalamus
      (2), optic chiasm (1) or deep cerebellum (1). Median age was 21 years (range 5
      41). Nine tumors received stereotactic radiotherapy (SRT). Three tumors received
      stereotactic radiosurgery (SRS), two of them to their choline positive regions.
      SRT median total dose was 50.4 Gy (40-50.4 Gy) in a median of 28 fractions (20
      28), using a median fraction dose of 1.8 Gy (1.8-2 Gy) to a median target volume
      of 6.5 cm(3). (2.4-33.57 cm(3)) SRS median dose was 18.75 Gy (16.66-20 Gy) to a
      median target volume of 1.69 cm(3) (0.74-2.22 cm(3)). Median follow-up time was
      37.5 months. Actuarial long-term progression-free and disease-specific survival
      probabilities were 73.3 and 91.7 %, respectively. No radiation-induced
      complications were observed. Stereotactic radiation therapy is a safe and
      effective modality to control progressive residual pilocytic astrocytomas. Better
      outcomes are obtained with SRT to entire tumor volumes than with SRS targeting
      choline positive tumor regions.

PMID- 22644537
TI  - Neurocognitive and sociodemographic functioning of glioblastoma long-term
      survivors.
AB  - An increasing number of patients with glioblastoma multiforme live longer than 3
      years after diagnosis (long-term survivors). Even so, little is known about their
      everyday performance and quality of life. We studied 17 glioblastoma patients
      surviving for longer than 3 years. We assessed all patients using the
      computerized neurocognitive assessment instrument NeuroCog FX test, the EORTC QLQ
      C30, the EORTC QLQ-BN20, the Hospital Anxiety and Depression Scale, the Ten-Meter
      Walking Test, the Nine Hole Peg Test, the Boston Aphasia Severity Scale, and the
      Activities of Daily Living and Instrumental Activities of Daily Living forms. We
      included 9 female and 8 male glioblastoma long-term survivors with a median age
      of 51 years (24-71). The majority of the patients (10/17) scored normal in the
      NeuroCog FX test. However, financial difficulties, reduced social and cognitive
      functioning, and future uncertainty were frequently reported. Three patients
      showed conspicuous depression scores, two had noticeable anxiety results.
      Drowsiness and fatigue were the most often reported physical complaints. There
      were 12/17 patients who were fully independent concerning activities of daily
      living and 14 patients (82%) showed >=90 points in the Barthel Index, but 6
      patients (35%) were impaired in their manual dexterity, and 1 patient in
      mobility. Glioblastoma long-term survivors show moderate impairment in their
      cognitive functions and more often neurological symptoms. However, the majority
      of these patients are able to manage their daily routine independently.
      Nevertheless, future prospects remain poor and patients suffer from financial
      difficulties.

PMID- 22644538
TI  - Cognitive flexibility in juvenile anorexia nervosa patients before and after
      weight recovery.
AB  - Deficits in set-shifting abilities have been robustly described in adult patients
      with anorexia nervosa (AN). These deficits are associated with behavioral traits,
      such as rigidity and perfectionism, and are independent of starvation. However,
      little is known about neurocognitive deficits in juvenile patients with AN. The
      brain circuits that support set shifting are not fully mature in these patients.
      One possibility is that neuroendocrinological changes, such as elevated cortisol
      levels, contributing to alterations in cognitive performance in individuals with
      AN. Set-shifting abilities (Visual Set-Shifting Task), cortisol levels, self
      reported perfectionism and obsessive personality traits were assessed in 28
      female adolescent patients with AN before (T0) and after (T1) weight
      rehabilitation and compared with 27 age- and IQ-matched healthy controls (CG).
      Compared with the CG, AN patients showed increased reaction times (RT) in shift
      trials (p < 0.001) and reduced error rates in both shift and non-shift trials
      across time points (p < 0.05). Across all subjects, perfectionism was associated
      with increased RTs during shift trials at T1 (r = 0.35, p < 0.05). Subjects with
      lower cortisol levels showed increased RTs and more errors in non-shift trials (p
      < 0.05). In contrast to the findings in adult patients, adolescent patients with
      AN did not display a marked deficit in set-shifting abilities. Instead, they
      demonstrated a perfectionistic cognitive style that was characterized by
      increased RTs in shift trials but improved accuracy. One could speculate that the
      shorter duration of illness and the incomplete maturation of the prefrontal
      cortices contribute to these findings.

PMID- 22644539
TI  - A possible pathophysiological role of tyrosine hydroxylase in Parkinson's disease
      suggested by postmortem brain biochemistry: a contribution for the special 70th
      birthday symposium in honor of Prof. Peter Riederer.
AB  - Postmortem brain biochemistry has revealed that the main symptom of movement
      disorder in Parkinson's disease (PD) is caused by a deficiency in dopamine (DA)
      at the nerve terminals of degenerating nigro-striatal DA neurons in the striatum.
      Since tyrosine hydroxylase (TH) is the rate-limiting enzyme for the biosynthesis
      of DA, TH may play an important role in the disease process of PD. DA regulated
      by TH activity is thought to interact with alpha-synuclein protein, which results
      in intracellular aggregates called Lewy bodies and causes apoptotic cell death
      during the aging process. Human TH has several isoforms produced by alternative
      mRNA splicing, which may affect activation by phosphorylation of serine residues
      in the N-terminus of TH. The activity and protein level of TH are decreased to
      cause DA deficiency in the striatum in PD. However, the homo-specific activity
      (activity/enzyme protein) of TH is increased. This increase in TH homo-specific
      activity suggests activation by increased phosphorylation at the N-terminus of
      the TH protein for a compensatory increase in DA synthesis. We recently found
      that phosphorylation of the N-terminal portion of TH triggers proteasomal
      degradation of the enzyme to increase TH turnover. We propose a hypothesis that
      this compensatory activation of TH by phosphorylation in the remaining DA neurons
      may contribute to a further decrease in TH protein and activity in DA neurons in
      PD, causing a vicious circle of decreasing TH activity, protein level and DA
      contents. Furthermore, increased TH homo-specific activity leading to an increase
      in DA may cause toxic reactive oxygen species in the neurons to promote
      neurodegeneration.

PMID- 22644540
TI  - CT- and fluoroscopy-guided percutaneous discectomy for lumbar radiculopathy
      related to disc herniation: a comparative prospective study comparing lateral to
      medial herniated discs.
AB  - OBJECTIVE: To evaluate and compare two groups of patients with sciatica due to
      intervertebral disc herniation with no neurologic deficit. The groups consisted
      of patients with intervertebral disc herniation in a medial location (group 1)
      and those in a lateral location (group 2). MATERIALS AND METHODS: A total of 200
      patients were included in the study and were followed for a minimum of 6 months.
      In our series, we treated 80 postero-lateral herniated discs (40% of cases), 46
      postero-medial herniated discs (23%), and 74 foraminal herniated discs (37%).
      Level L3-L4 was treated in 30 cases (15%), L4-L5 in 98 cases (49%), and L5-S1 in
      72 cases (36%). The procedure was performed under dual guidance: fluoroscopic and
      CT. A helical probe was activated. It penetrates the herniated disc and causes
      the pulpous material to be mechanically evacuated through the probe. All 200
      patients were followed for a minimum of 6 months. RESULTS: In group 1, the
      patients had a mean pain score of 7.9 +/- 2.5 VAS units (range 6-10 units) prior
      to intervention. This was reduced to 3.2 +/- 2.1 VAS units (range 0-10 units) at
      48 h follow-up and increased to 3.9 +/- 1.2 VAS units (range 0-10 VAS units) at 1
      month follow-up and further reduced to 2.7 +/- 1.2 units (range 0-10 VAS units)
      at 6 month follow-up. In group 2, the patients had a mean pain score of 8.2 +/-
      3.2 VAS units (range 6-10 units) prior to intervention. This was reduced to 2.8
      +/- 1.5 VAS units (range 0-10 units) at 48 h follow-up and decreased to 1.5 +/-
      0.9 VAS units (range 0-10 units) at 1 month and further reduced to 1.1 +/- 0.5
      VAS units (range 0-10 units) at 6 months. CONCLUSION: Our study showed that
      results were more satisfactory for the hernia located laterally (postero-lateral,
      foraminal, and extra-foraminal) as compared to the hernia located
      posteromedially.

PMID- 22644541
TI  - Introduction of an alternative standardized radiographic measurement method to
      evaluate volar angulation in subcapital fractures of the 5th metacarpal.
AB  - OBJECTIVE: The purpose of the present study was to compare the intra- and
      interobserver reliability of two different measurement methods for volar
      angulation of the 5th metacarpal (MC) in an attempt to establish a new standard
      measurement method to reduce interobserver discrepancies for therapeutic
      decisions. MATERIALS AND METHODS: Twenty patients with subcapital fractures of
      the 5th MC were radiologically investigated. Imaging consisted of a radiographs
      in antero-posterior and precise lateral view in addition to a CT scan of the 5th
      MC. Measurement of volar angulation was accomplished using the conventional and
      the shaft articular surface (SAS) method. The measurements of five investigators
      were exported to a spreadsheet for statistical analysis to evaluate the intra-and
      interobserver reliability. RESULTS: The conventional technique showed large
      differences among the investigators and poor interobserver reliability (W = 0.328
      and 0.307) both at injury (p = 0.001) and at follow-up (p = 0.189). The
      intraobserver concordance of all investigators showed better results with the SAS
      than with the conventional technique. With the SAS technique, no statistically
      significant difference among the investigators could be detected at either the
      time of injury (p = 0.418) or at follow-up (p = 0.526) with excellent
      interobserver reliability (W = 0.051 and W = 0.041). Evaluation of volar
      angulation at follow-up using CT scans did not show any statistically significant
      difference between the techniques with better correlation among the observers
      with the SAS technique (p = 0.838). CONCLUSIONS: The interobserver correlation of
      volar angulation with lateral radiographs using the conventional technique was
      insufficient. Therefore, we recommend the use of the novel SAS technique as
      standardized measurement method which showed higher accuracy and interobserver
      reliability in order to facilitate the choice of adequate treatment option.
      CLINICAL RELEVANCE: A CT scan should be performed in cases with ambivalent
      treatment options. LEVEL OF EVIDENCE: Evidence-Based Medicine Level II.

PMID- 22644542
TI  - The feasibility and test-retest reliability of the Dutch Swal-Qol adapted
      interview version for dysphagic patients with communicative and/or cognitive
      problems.
AB  - PURPOSE: The adaptation of the Dutch Swal-Qol questionnaire to an interview
      format suitable for dysphagic patients with communicative and/or cognitive
      problems and evaluation of the feasibility and test-retest reliability. METHODS:
      An observational study with two measurements within a 2-week time period in a
      sample of 57 stroke patients with dysphagia in a nursing home environment. The
      interview version of the Swal-Qol was evaluated in the total group and in
      subgroups of patients with and without communicative and/or cognitive problems.
      RESULTS: The constructed interview version was considered feasible from an
      expert's and patient's point of view. The overall score and seven subscales of
      the Swal-Qol showed an excellent test-retest reliability (k > 0.75), and two
      subscales were considered good (k > 0.60). CONCLUSIONS: This study showed that
      using a structured, and at the same time flexible, interview format tailored to
      the individual needs of stroke patients enhances the feasibility and does not
      compromise the test-retest reliability.

PMID- 22644543
TI  - Assessing the effects of oral health-related variables on quality of life in
      Taiwanese adults.
AB  - PURPOSE: The impact of oral health status on Taiwanese adults' quality of life
      has not been measured definitively. This study evaluated the effects of oral
      health-related variables on quality of life among adults in Taiwan. METHODS: A
      cross-sectional study design with secondary database analysis was adopted.
      Information about oral health-related variables in adults aged 18-64 years was
      collected from the National Health Interview Survey and quality-of-life data from
      the Short-Form Health Survey (SF-36). Univariate and multivariate regression
      analysis was used to determine risk factors for oral health and associations
      between oral health and eight domains of quality of life defined by the SF-36.
      RESULTS: Gender (P < 0.001), marital status (P < 0.001), monthly income (P <
      0.001), disease history (P < 0.001), betel nut chewing (P < 0.001), oral hygiene
      (P < 0.001), oral health status (P < 0.001), and dental care utilization (P =
      0.001) had significant effects on general health as an aspect of quality of life;
      gender (P < 0.001), marital status (divorced, P < 0.001), income level (20,000
      80,000 NTD, P < 0.001), disease history (P < 0.001), oral hygiene, oral health
      related food choice limitations (P < 0.001), and dental care utilization (P <
      0.001) had significant effects on general mental health. Subjects who practiced
      dental self-care with tooth brushing had significantly higher social functioning
      scores than those who did not (P < 0.001). Significant differences were also
      found in scale items for physical functioning, role limitations due to physical
      health, bodily pain, vitality, and role limitations due to emotional problems
      (all P < 0.001). CONCLUSIONS: Demographic (i.e., age, gender, and marital status
      and income levels) and oral health-related factors (i.e., oral hygiene, dental
      visits, disease history, and lifestyle factors such as cigarette smoking, alcohol
      use, and betel nut chewing) are all significantly associated with oral health
      related quality of life in Taiwanese adults.

PMID- 22644544
TI  - Nephrotic syndrome.
AB  - The pathogenetic basis of idiopathic nephrotic syndrome, a common childhood
      glomerulopathy, is being explored. While initial evidence supported an imbalance
      of T helper responses, recent studies suggest alterations in both innate and
      adaptive immune responses, including evidence for impaired T regulatory function.
      The central role of the podocyte in causing proteinuria is confirmed by the
      observation of mutations in key podocyte proteins in steroid resistant nephrotic
      syndrome and experimental evidence of altered podocyte signaling and cytoskeletal
      organization. The outcome and management of idiopathic nephrotic syndrome in
      children is determined by the response to corticosteroids and the frequency of
      relapses. While patients with steroid sensitive nephrotic syndrome have a
      favorable long term outcome, almost half of them relapse frequently and are at
      risk of adverse effects of corticosteroids. Although various non-corticosteroid
      immunosuppressive agents are used to prolong disease remission, careful
      monitoring is required for the potential adverse effects. Calcineurin inhibitors
      have emerged as the choice of therapy in patients with steroid resistant
      nephrotic syndrome. However, the management of this form of the disease is
      particularly challenging because of the variable response to immunosuppression,
      therapy-related significant adverse effects and high rates of disease progression
      to end stage renal disease. Patients with both corticosteroid sensitive and
      resistant forms of the disease are at risk of complications of disease, and
      require close monitoring and repeated counseling.

PMID- 22644545
TI  - Addressing pediatric medical training needs in noncommunicable diseases.
AB  - The importance of addressing non-communicable diseases (NCDs) has been identified
      by health care leaders in India and around the world. Calls to action have been
      made to address this issue, including the creation of effective surveillance and
      research systems across South Asia. These efforts include collaboration within
      India at the local, regional, and national levels to support these initiatives.
      In addition to these efforts, it is critical to assess and strengthen medical
      training in NCDs. This can be done by providing clinicians with curriculum
      development tools to augment their clinical skills, as well as enabling them to
      advocate and role model as educators. The authors provide recommendations on how
      clinicians can address the threat of NCDs as educators, role models and advocates
      for improved pediatric NCD training.

PMID- 22644546
TI  - Anterograde episodic memory in Korsakoff syndrome.
AB  - A profound anterograde memory deficit for information, regardless of the nature
      of the material, is the hallmark of Korsakoff syndrome, an amnesic condition
      resulting from severe thiamine (vitamin B1) deficiency. Since the late nineteenth
      century when the Russian physician, S. S. Korsakoff, initially described this
      syndrome associated with "polyneuropathy," the observed global amnesia has been a
      primary focus of neuroscience and neuropsychology. In this review we highlight
      the historical studies that examined anterograde episodic memory processes in KS,
      present a timeline and evidence supporting the myriad theories proffered to
      account for this memory dysfunction, and summarize what is known about the
      neuroanatomical correlates and neural systems presumed affected in KS. Rigorous
      study of KS amnesia and associated memory disorders of other etiologies provide
      evidence for distinct mnemonic component processes and neural networks imperative
      for normal declarative and nondeclarative memory abilities and for mnemonic
      processes spared in KS, from whence emerged the appreciation that memory is not a
      unitary function. Debate continues regarding the qualitative and quantitative
      differences between KS and other amnesias and what brain regions and neural
      pathways are necessary and sufficient to produce KS amnesia.

PMID- 22644561
TI  - Unusually increased metaiodobenzylguanidine uptake in a gastrointestinal stromal
      tumor of the stomach.
AB  - A 70-year-old woman with a submucosal gastric tumor was referred to our hospital
      for surgical treatment. Upon examination, it was found that she had hypertension,
      and abdominal computed tomography revealed swelling on both adrenal glands. The
      patient was examined with gamma camera imaging and iodine-123
      metaiodobenzylguanidine (MIBG), because her hypertension was thought to be due to
      a suspected adrenomedullary tumor. The planar image showed an unexpected abnormal
      uptake of MIBG in the upper abdomen. On single-photon emission computed
      tomographic images, the area of abnormal tracer uptake was thought to correspond
      to the known gastric tumor. The surgical procedure and histological assessments
      revealed that the gastric tumor was a gastrointestinal stromal tumor (GIST). MIBG
      can accumulate in GISTs as well as in neuroendocrine tumors of the medulla of the
      adrenal glands. Although the cause of radiolabeled MIBG uptake in GISTs is
      uncertain, further studies are necessary to establish the significance of MIBG
      scintigraphy in GIST imaging.

PMID- 22644560
TI  - The utility of FDG-PET/CT as an effective tool for detecting recurrent colorectal
      cancer regardless of serum CEA levels.
AB  - PURPOSE: Tumor recurrence of colorectal cancers (CRC) is generally followed up by
      analyses of the serum carcinoembryonic antigen (CEA) levels. However, recent
      evidence suggests that tumor recurrence can also be visualized by 18F-fluoro
      deoxyglucose emission tomography/computed tomography (FDG-PET/CT) in patients
      with normal CEA levels. We retrospectively evaluated the diagnostic performance
      of FDG-PET/CT in patients with suspected recurrence of CRC by comparing PET/CT
      performance in patients with normal CEA levels with PET/CT performance in
      patients with elevated CEA levels. METHODS: A total of 235 patients with CRC who
      had been treated with surgery and/or chemotherapy/radiotherapy underwent PET/CT
      for the detection of tumor recurrence. The patients [96 females and 139 males;
      age (mean +/- SD) 59.9 +/- 12.6 years; range 18-85] were divided into 2 groups
      based on whether their CEA levels were normal (<5 ng/ml) (Group 1, n = 118) or
      elevated (>5 ng/ml) (Group 2, n = 117). All of the patients had suspected
      recurrence based on raised CEA levels, clinical symptoms, and/or tumor detection
      using other imaging modalities. RESULTS: Of the 235 patients, 172 (73.1 %) had
      disease recurrence confirmed by a pathological examination (either biopsy or
      surgical exploration) or clinical follow-up studies. The FDG-PET/CT study yielded
      a true positive in detecting recurrence in 169 (71.9 %) patients, a true negative
      in 53 (22.5 %) patients, a false negative in 3 (1.2 %) patients and a false
      positive in 10 (4.2 %) patients. CRC recurrence was detected in 64.4 % (76/118)
      and 88 % (103/117) patients in Group 1 and Group 2 with FDG-PET/CT, respectively.
      The sensitivity, specificity, positive predictive value (PPV), negative
      predictive value (NPV) and accuracy of the FDG-PET/CT study for establishing
      recurrence were 100, 84, 89.4, 100 and 93.2 %, respectively, for Group 1; by
      contrast, these parameters were 97.1, 84.6, 98, 78.5 and 95.7 %, respectively,
      for Group 2. The number of patients with hepatic and extra-hepatic metastases,
      such as lung and abdominal lymph node metastasis, detected with FDG-PET/CT was
      significantly different in Group 1 than in Group 2; however, the number of
      patients with local recurrence and peritoneal implants detected with FDG-PET/CT
      was not different between the two groups. CONCLUSIONS: FDG-PET/CT can accurately
      detect tumor recurrence in patients with suspected recurrent CRC, even for
      patients with normal CEA levels.

PMID- 22644562
TI  - Expression of stromal genes associated with the angiogenic response are not
      differentiated between human tumour xenografts with divergent vascular
      morphologies.
AB  - Human tumour xenografts have commonly been used to explore the mechanisms of
      tumour angiogenesis and the interaction of tumour cells with their
      microenvironment, as well as predict potential utility of anti-angiogenic
      inhibitors across different tumour types. To investigate how well human tumour
      xenografts can be used to differentiate the effects of stromal targeting agents
      we performed a comparative assessment of the murine angiogenic response across a
      panel of pre-clinical tumour xenografts. By analysing a panel of 22 tumour
      xenografts with a range of vascular morphologies, micro-vessel densities and
      levels of fibroblast and inflammatory infiltrate, we have examined the
      relationship between angiogenic stroma and human tumour models. These models were
      studied using a combination of immunohistochemistry and species specific mRNA
      profiling to differentiate the tumour and stromal transcript mRNA profiles.
      Principal Component Analysis (PCA) and regression analysis was used to
      investigate the transcriptional relationships between the individual models and
      the correlation with the stromal architecture. We found the human tumour cell
      expressed factors to be independent of the murine host responses such as
      microvessel density, and fibroblast or macrophage cellular infiltrate. Moreover
      mRNA profiling of the mouse stroma suggested that the host response to the
      different tumours was relatively uniform despite differences in stromal
      structures within the tumour. Supporting this, models with different stromal
      compositions responded similarly to cediranib, a small molecule inhibitor of VEGF
      signalling. The data indicate that although the angiogenic response to the tumour
      results in reproducible stromal architectures, these responses are not
      differentiated at the level of gene expression.

PMID- 22644563
TI  - Positron emission tomography imaging of tumor angiogenesis and monitoring of
      antiangiogenic efficacy using the novel tetrameric peptide probe 64Cu-cyclam-RAFT
      c(-RGDfK-)4.
AB  - 64Cu-cyclam-RAFT-c(-RGDfK-)4 is a novel multimeric positron emission tomography
      (PET) probe for alphaVbeta3 integrin imaging. Its uptake and alphaVbeta3
      expression in tumors showed a linear correlation. Since alphaVbeta3 integrin is
      strongly expressed on activated endothelial cells during angiogenesis, we aimed
      to determine whether 64Cu-cyclam-RAFT-c(-RGDfK-)4 PET can be used to image tumor
      angiogenesis and monitor the antiangiogenic effect of a novel multi-targeted
      tyrosine kinase inhibitor, TSU-68. Athymic nude mice bearing human hepatocellular
      carcinoma HuH-7 xenografts, which expressed negligible alphaVbeta3 levels on the
      tumor cells, received intraperitoneal injections of TSU-68 or the vehicle for 14
      days. Antiangiogenic effects were determined at the end of therapy in terms of
      64Cu-cyclam-RAFT-c(-RGDfK-)4 uptake evaluated using PET, biodistribution assay,
      and autoradiography, and they were compared with microvessel density (MVD)
      determined by CD31 immunostaining. 64Cu-cyclam-RAFT-c(-RGDfK-)4 PET enabled clear
      tumor visualization by targeting the vasculature, and the biodistribution assay
      indicated high tumor-to-blood and tumor-to-muscle ratios of 31.6 +/- 6.3 and 6.7
      +/- 1.1, respectively, 3 h after probe injection. TSU-68 significantly slowed
      tumor growth and reduced MVD; these findings were consistent with a significant
      reduction in the tumor 64Cu-cyclam-RAFT-c(-RGDfK-)4 uptake. Moreover, a linear
      correlation was observed between tumor MVD and the corresponding standardized
      uptake value (SUV) (r = 0.829, P = 0.011 for SUV(mean); r = 0.776, P = 0.024 for
      SUV(max)) determined by quantitative PET. Autoradiography and immunostaining
      showed that the distribution of intratumoral radioactivity and tumor vasculature
      corresponded. We concluded that 64Cu-cyclam-RAFT-c(-RGDfK-)4 PET can be used for
      in vivo angiogenesis imaging and monitoring of tumor response to antiangiogenic
      therapy.

PMID- 22644564
TI  - Wear resistant performance of highly cross-linked and annealed ultra-high
      molecular weight polyethylene against ceramic heads in total hip arthroplasty.
AB  - The purpose of this study was to examine the effects of ceramic femoral head
      material, size, and implantation periods on the wear of annealed, cross-linked
      ultra-high molecular weight polyethylene (UHMWPE) (XLPE) in total hip
      arthroplasty compared to non-cross-linked conventional UHMWPE (CPE). XLPE was
      fabricated by cross-linking with 60 kGy irradiation and annealing. Femoral heads
      made from zirconia and alumina ceramics and cobalt-chrome (CoCr) of 22 or 26 mm
      diameter were used. In this retrospective cohort study, the femoral head
      penetration into the cup was measured digitally on radiographs of 367 hips with
      XLPE and 64 hips with CPE. The average follow-up periods were 6.3 and 11.9 years,
      respectively. Both XLPE creep and wear rates were significantly lower than those
      of CPE (0.19 mm vs. 0.44 mm, 0.0001 mm/year vs. 0.09 mm/year, respectively).
      Zirconia displayed increased wear rates compared to alumina in CPE; however,
      there was no difference among head materials in XLPE (0.0008, 0.00007, and -0.009
      mm/year for zirconia, alumina, and CoCr, respectively). Neither head size or
      implantation period impacted XLPE wear. In contrast to CPE, XLPE displayed low
      wear rates surpassing the effects of varying femoral head material, size,
      implantation period, and patient demographics. Further follow-up is required to
      determine the long-term clinical performance of the annealed XLPE.

PMID- 22644565
TI  - Extremophilic Acinetobacter strains from high-altitude lakes in Argentinean Puna:
      remarkable UV-B resistance and efficient DNA damage repair.
AB  - High-Altitude Andean Lakes (HAAL) of the South American Andes are almost
      unexplored ecosystems of shallow lakes. The HAAL are recognized by a remarkably
      high UV exposure, strong changes in temperature and salinity, and a high content
      of toxic elements, especially arsenic. Being exposed to remarkably extreme
      conditions, they have been classified as model systems for the study of life on
      other planets. Particularly, Acinetobacter strains isolated from the HAAL were
      studied for their survival competence under strong UV-B irradiation. Clinical
      isolates, Acinetobacter baumannii and Acinetobacter johnsonii, served as
      reference material. Whereas the reference strains rapidly lost viability under UV
      B irradiation, most HAAL-derived strains readily survived this exposure and
      showed less change in cell number after the treatment. Controls for DNA repair
      activity, comparing dark repair (DR) or photo repair (PR), gave evidence for the
      involvement of photolyases in the DNA repair. Comparative measurements by HPLC
      mass spectrometry detected the number of photoproducts: bipyrimidine dimers under
      both PR and DR treatments were more efficiently repaired in the HAAL strains (up
      to 85 % PR and 38 % DR) than in the controls (31 % PR and zero DR ability).
      Analysis of cosmid-cloned total genomic DNA from the most effective DNA
      photorepair strain (Ver3) yielded a gene (HQ443199) encoding a protein with clear
      photolyase signatures belonging to class I CPD-photolyases. Despite the
      relatively low sequence similarity of 41 % between the enzymes from Ver3 and from
      E. coli (PDB 1DNPA), a model-building approach revealed a high structural
      homology to the CPD-photolyase of E. coli.

PMID- 22644567
TI  - Two different sources of water for the early solar nebula.
AB  - Water is essential for life. This is a trivial fact but has profound implications
      since the forming of life on the early Earth required water. The sources of water
      and the related amount of delivery depend not only on the conditions on the early
      Earth itself but also on the evolutionary history of the solar system. Thus we
      ask where and when water formed in the solar nebula-the precursor of the solar
      system. In this paper we explore the chemical mechanics for water formation and
      its expected abundance. This is achieved by studying the parental cloud core of
      the solar nebula and its gravitational collapse. We have identified two different
      sources of water for the region of Earth's accretion. The first being the
      sublimation of the icy mantles of dust grains formed in the parental cloud. The
      second source is located in the inner region of the collapsing cloud core - the
      so-called hot corino with a temperature of several hundred Kelvin. There, water
      is produced efficiently in the gas phase by reactions between neutral molecules.
      Additionally, we analyse the dependence of the production of water on the initial
      abundance ratio between carbon and oxygen.

PMID- 22644566
TI  - Inversion concept of the origin of life.
AB  - The essence of the inversion concept of the origin of life can be narrowed down
      to the following theses: 1) thermodynamic inversion is the key transformation of
      prebiotic microsystems leading to their transition into primary forms of life; 2)
      this transformation might occur only in the microsystems oscillating around the
      bifurcation point under far-from-equilibrium conditions. The transformation
      consists in the inversion of the balance "free energy contribution / entropy
      contribution", from negative to positive values. At the inversion moment the
      microsystem radically reorganizes in accordance with the new negentropy (i.e.
      biological) way of organization. According to this approach, the origin-of-life
      process on the early Earth took place in the fluctuating hydrothermal medium. The
      process occurred in two successive stages: a) spontaneous self-assembly of
      initial three-dimensional prebiotic microsystems composed mainly of hydrocarbons,
      lipids and simple amino acids, or their precursors, within the temperature
      interval of 100-300 degrees C (prebiotic stage); b) non-spontaneous synthesis of
      sugars, ATP and nucleic acids started at the inversion moment under the
      temperature 70-100 degrees C (biotic stage). Macro- and microfluctuations of
      thermodynamic and physico-chemical parameters able to sustain this way of
      chemical conversion have been detected in several contemporary hydrothermal
      systems. A minimal self-sufficient unit of life on the early Earth was a
      community of simplest microorganisms (not a separate microorganism).

PMID- 22644568
TI  - Perceived exertion as a tool to self-regulate exercise in individuals with
      tetraplegia.
AB  - The purpose of this investigation was to examine the use of subjective rating of
      perceived exertion (RPE) as a tool to self-regulate the intensity of wheelchair
      propulsive exercise in individuals with tetraplegia. Eight motor complete
      tetraplegic (C5/6 and below; ASIA Impairment Scale = A) participants completed a
      submaximal incremental exercise test followed by a graded exercise test to
      exhaustion to determine peak oxygen uptake (VO2(peak)) on a wheelchair ergometer.
      On a separate day, a 20-min exercise bout was completed at an individualised
      imposed power output (PO) equating to 70 % of VO2(peak). On a third occasion,
      participants were instructed to maintain a workload equivalent to the average RPE
      for the 20-min imposed condition. VO2(peak), heart rate (HR) and PO were measured
      at 1-min intervals and blood lactate concentration [BLa(-)] was measured at 0, 10
      and 20 min. No differences (P > 0.17) were found between mean VO2(peak), %
      VO2(peak), HR, % HR(peak), [BLa(-)], velocity or PO between the imposed and RPE
      regulated trials. No significant (P > 0.05) time-by-trial interaction was present
      for VO2(peak) data. A significant interaction (P < 0.001) for the PO data
      represented a trend for an increase in PO from 10 min to the end of exercise
      during the RPE-regulated condition. However, post hoc analysis revealed none of
      the differences in PO across time were significant (P > 0.05). In conclusion,
      these findings suggest that RPE can be an effective tool for self-regulating 20
      min of wheelchair propulsion in a group of trained participants with tetraplegia
      who are experienced in wheelchair propulsion.

PMID- 22644569
TI  - Heat stress attenuates the increase in arterial blood pressure during isometric
      handgrip exercise.
AB  - The purpose of this study was to examine arterial blood pressure responses during
      isometric handgrip (IHG) exercise performed at increasing levels of heat stress.
      Ten male subjects performed 1 min of IHG exercise at 60 % of maximal voluntary
      contraction under no heat stress (NHS), moderate heat stress [MHS, 0.6  degrees C
      increase in esophageal temperature (T (es))] and high heat stress (HHS, 1.4 
      degrees C increase in T (es)). For all conditions, IHG exercise significantly
      elevated mean arterial pressure (MAP) (NHS: 124 +/- 6 vs. 90 +/- 4 mmHg, MHS: 112
      +/- 6 vs. 89 +/- 6 mmHg, HHS: 107 +/- 7 vs. 91 +/- 5 mmHg, P <= 0.05) and cardiac
      output (CO) (NHS: 9.0 +/- 1.5 vs. 6.1 +/- 0.6 L/min, MHS: 9.8 +/- 1.8 vs. 7.6 +/-
      1.3 L/min, HHS: 10.0 +/- 2.0 vs. 8.5 +/- 1.9 L/min, P <= 0.05) relative to
      baseline, whereas no differences in total peripheral resistance (TPR) were
      observed (P > 0.05). However, the relative increases in MAP and CO were
      significantly reduced during MHS (MAP: 23 +/- 6 mmHg, CO: 2.1 +/- 0.9 L/min) and
      HHS (MAP: 16 +/- 7 mmHg, CO: 1.5 +/- 0.8 L/min) compared to NHS (34 +/- 5 mmHg,
      CO: 2.9 +/- 1.1 L/min, P <= 0.05). Furthermore, these elevations were
      significantly attenuated during HHS compared to MHS (P <= 0.05). Our findings
      show that heat stress attenuates the increase in arterial blood pressure during
      isometric handgrip exercise and this attenuation is cardiac output dependent,
      since TPR did not change during exercise for all heat stress conditions.

PMID- 22644570
TI  - Regenerative responses in slow- and fast-twitch muscles following moderate
      contusion spinal cord injury and locomotor training.
AB  - The aim of this study was to use the rat moderate spinal cord contusion model to
      investigate the effects of incomplete spinal cord injury (SCI) on the muscle
      regeneration process, comparing regeneration of slow-twitch plantarflexor soleus
      muscle and fast-twitch dorsiflexor tibialis anterior (TA) muscle. Additionally,
      we wanted to examine the effect of a week of locomotor training following
      incomplete SCI on the muscle regeneration process in these muscles and also
      determine if a week of similar locomotor training is sufficient to initiate
      muscle regeneration in control, non-injured rats. Thirty-two, adult, female,
      Sprague-Dawley rats were chosen for the study. Moderate, midthoracic contusion
      SCIs were produced using a NYU (New York University) impactor in all rats except
      controls. Animals were randomly assigned to treadmill training or untrained
      groups. Rats in the treadmill training group were manually treadmill trained
      starting at 1 week after SCI, for 10 bouts (2 sessions of 20 min of actual
      stepping) over 5 days and control rats in the training group received similar
      training. Our results indicate that a muscle regenerative response was initiated
      only in the slow-twitch soleus muscle in the initial 2 weeks following SCI, the
      addition of 1 week of locomotor treadmill training led to a significant increase
      in soleus regenerative process. No significant regenerative process was observed
      in the fast-twitch TA. Increased muscle regeneration in soleus is suggested by
      our findings of increased expression of (1) insulin-like growth factor-1,
      involved in the activation of satellite cells; (2) Pax7, a marker of satellite
      cell activation; (3) myogenin, a muscle regulatory protein; and (4) embryonic
      myosin, an indicator of new muscle fiber formation. Locomotor training in
      control, non-injured animals did not induce similar changes towards the
      regenerative process.

PMID- 22644571
TI  - Cleavage of Atg3 protein by caspase-8 regulates autophagy during receptor
      activated cell death.
AB  - Autophagy is an evolutionarily conserved mechanism contributing to cell survival
      under stress conditions including nutrient and growth factor deprivation.
      Connections and cross-talk between cell death mechanisms and autophagy is under
      investigation. Here, we describe Atg3, an essential regulatory component of
      autophagosome biogenesis, as a new substrate of caspase-8 during receptor
      mediated cell death. Both, tumor necrosis factor alpha and tumor necrosis factor
      related apoptosis inducing ligand induced cell death was accompanied by Atg3
      cleavage and this event was inhibited by a pan-caspase inhibitor (zVAD) or a
      caspase-8-specific inhibitor (zIETD). Indeed, caspase-8 overexpression led to
      Atg3 degradation and this event depended on caspase-8 enzymatic activity.
      Mutation of the caspase-8 cleavage site on Atg3 abolished its cleavage both in
      vitro and in vivo, demonstrating that Atg3 was a direct target of caspase-8.
      Autophagy was inactive during apoptosis and blockage of caspases or
      overexpression of a non-cleavable Atg3 protein reestablished autophagic activity
      upon death receptor stimulation. In this system, autophagy was important for cell
      survival since inhibition of autophagy increased cell death. Therefore, Atg3
      provides a novel link between apoptosis and autophagy during receptor-activated
      cell death.

PMID- 22644572
TI  - Label-free monitoring of apoptosis by surface plasmon resonance detection of
      morphological changes.
AB  - Apoptosis can be routinely characterized using biomolecular markers such as in
      the TUNEL and the annexin V assays or by using fluorescent caspase substrates.
      Apoptosis can also be semi-quantitatively characterized using microscopy, which
      targets morphological features such as cell rounding, nuclear condensation and
      fragmentation as well as cell membrane blebbing. This label-free approach
      provides a limited resolution for the evolution of these events in time and
      relies heavily on subjective identification of the morphological features. Here
      we propose a label-free assay based on surface plasmon resonance (SPR) detection
      of minute morphology changes occurring as a result of apoptosis induction in an
      endothelial cell model (EA.hy926). At first, annexin V assays confirmed that our
      cellular model was responsive to TRAIL over a 12-hour period. Then, we show that
      SPR allows accurate monitoring of apoptosis by measuring (1) the duration of the
      latency period during which the apoptotic signal is integrated by the initiator
      caspases and transmitted to the executioner caspases, (2) the rate of the
      execution phase in which death substrates are cleaved and morphological changes
      occur, and (3) the total extent of apoptosis. Using these parameters, we
      characterized the responses obtained with TRAIL (EA.hy926, HeLa, AD-293) and the
      anti-Fas antibody (HeLa) for the extrinsic pathways and UV exposure (HeLa) for
      the intrinsic pathways. By comparing the SPR time-course of apoptosis with phase
      contrast micrographs, we demonstrate that the cell morphological hallmarks of
      apoptosis are the major contributors to the SPR signal. Altogether, our results
      validate the use of SPR as an accurate label-free assay for the real-time
      monitoring of apoptosis-triggered cell morphological changes.

PMID- 22644575
TI  - Leading ladies: leadership of group movements in a pair-living, co-dominant,
      monomorphic primate across reproductive stages and fruit availability seasons.
AB  - For gregarious species, individuals must maintain cohesion while minimizing the
      costs of coordinated travel. Leaders of group movements potentially influence
      energy expenditure, energy intake, and predation risk for individuals in the
      group, which can have important fitness consequences. Models of pair-living
      species predict that energetic asymmetries lead to an emergent leader, with those
      in greater need leading. We investigated sex differences in leadership in pairs
      of red-bellied lemurs, Eulemur rubriventer, a monomorphic species with bisexual
      dispersal and no discernible hierarchy, to determine whether higher energetic
      requirements by adult females lead to female leadership. We collected leadership
      data in Ranomafana National Park, Madagascar on six groups of habituated E.
      rubriventer for 13 consecutive months between 2004-2005. To determine whether
      females led group movements more than males, we examined the difference in
      leadership frequencies of progressions in adult males and adult females within
      each group (n = 1,346 progressions). We further investigated the behavioral
      context (i.e. travel followed by feeding or not) and seasonal contexts (fruit
      availability, reproduction) of leadership. Group leadership was distributed, with
      different individuals leading the group at different times. However, females led
      significantly more than males, a pattern which was consistent in both feeding and
      non-feeding contexts and throughout all fruiting seasons and reproductive stages.
      While disparities in energetic status among the sexes may impact leadership in
      this species, leadership did not differ with changes in food availability or
      reproductive stage, and thus we were unable to determine whether female
      leadership might be related to changes in energetic status. Females may have
      higher energetic needs than males at all times, not merely seasonally, or female
      leadership may be unrelated to immediate energetic need. Rather, female
      leadership may be a legacy of female dominance not currently expressed in other
      contexts.

PMID- 22644576
TI  - Reductions in primate abundance and diversity in a multiuse protected area:
      synergistic impacts of hunting and logging in a congo basin forest.
AB  - This article explores spatial and temporal changes in diurnal primate abundance
      and behavior in response to hunting, logging, and conservation at the Dzanga
      Sangha Dense Forest Reserve (RDS), Central African Republic over time. We use a
      combination of line-transect surveys in 2002 and 2009 (N = 540 km) and
      ethnographic interviews (N = 210) to investigate changes in the status of
      cercopithecines and colobines at RDS, with additional comparisons to earlier
      work. This protected area was lightly logged in the 1970s and the park was
      gazetted in 1990, with multiple-use reserve sectors allocated. Since the park's
      inception, hunting and the trade of primates have increased, along with human
      migration, greater accessibility of arms, and reduction of preferred ungulate
      prey. Primates have declined in both the park and reserve sectors. Our data
      further suggest that at RDS hunting has had a greater impact on primate diversity
      and abundance than logging. We have identified changes in species-specific
      vulnerability to hunting over time, with Cercopithecus nictitans and Lophocebus
      albigena initially having appeared to be relatively resistant to hunting pressure
      in 2002. However, subsequently as gun hunting has increased at RDS, these species
      have become vulnerable. Although monkeys at RDS have been responding behaviorally
      to increased gun hunting, they are not able to keep pace with changing hunting
      practices. This study allows us to begin to understand synergistic impacts of
      hunting and logging, necessary if we are to recommend strategies to better secure
      the future of primates in multiuse protected areas.

PMID- 22644577
TI  - The effects of group size and reproductive status on vigilance in captive
      Callithrix jacchus.
AB  - Previous work on mammals and birds has often demonstrated a negative relationship
      between group size and individual vigilance. However, this relationship has
      received only weak support in nonhuman primates. This result may be due to the
      failure to distinguish different forms of vigilance such as antipredatory
      vigilance and social monitoring. Here, we tested the effects of group size,
      reproductive status (breeding vs. nonbreeding), and sex on antipredatory
      vigilance and social monitoring in captive common marmosets (Callithrix jacchus).
      Behavioral observations using one-zero sampling were conducted on adult members
      of three captive groups of small, medium, and large size. Data were analyzed
      using a series of general linear models (GLMs) analyses of covariance (ANCOVAs).
      We found an overall negative group size effect on antipredatory vigilance and
      that breeders, especially breeding males, were significantly more vigilant than
      nonbreeders. Conversely, we found that social monitoring increased with group
      size. Unlike the results for antipredatory vigilance, neither breeders and
      nonbreeders nor males and females differed in their amounts of social monitoring.
      However, the effect of group size appeared to differ for nonbreeding males
      compared to all other adults. Our results generally support the idea that
      individuals in larger groups are safer with breeding males likely playing a
      prominent role in protection from predation. The increase in social monitoring
      may be related to increased reproductive competition with the presence of adult
      offspring, but future studies need to clarify the target of social monitoring in
      both breeders and nonbreeders. Overall, the study underlines the importance of
      distinguishing different forms of vigilance and other factors as they may
      confound the effects of group size on antipredatory vigilance.

PMID- 22644578
TI  - High frequency of leaf swallowing and its relationship to intestinal parasite
      expulsion in "village" chimpanzees at Bulindi, Uganda.
AB  - Self-medication by great apes to control intestinal parasite infections has been
      documented at sites across Africa. Chimpanzees (Pan troglodytes) swallow the
      leaves of certain plant species whole, without chewing. Previous studies
      demonstrated a relationship between chimpanzee leaf swallowing and expulsion of
      nematode worms (Oesophagostomum sp.) and tapeworms (Bertiella sp.) in dung. We
      investigated the relationship between leaf swallowing and parasite expulsion in
      chimpanzees inhabiting a fragmented forest-farm mosaic at Bulindi, Uganda. During
      13 months whole undigested leaves occurred in chimpanzee dung at a considerably
      higher frequency (10.4% of dungs) than at other sites (0.4-4.0%). Leaf swallowing
      occurred year-round and showed no pronounced seasonality. Chimpanzees egested
      adults of multiple species of Oesophagostomum (including O. stephanostomum) and
      proglottids of two tapeworms-Bertiella sp. and probably Raillietina sp. The
      latter may not be a true infection, but the byproduct of predation on domestic
      fowl. Compared to previous studies, the co-occurrence of whole leaves and
      parasites in chimpanzee dung was low. Whereas the presence of leaves in dung
      increased the probability of adult nematode expulsion, no association between
      leaf swallowing and the shedding of tapeworm proglottids was apparent.
      Anthropogenic habitat changes have been linked to alterations in host-parasite
      interactions. At Bulindi, deforestation for agriculture has increased contact
      between apes and people. Elevated levels of leaf swallowing could indicate these
      chimpanzees are especially vulnerable to parasite infections, possibly due to
      environmental changes and/or increased stress levels arising from a high
      frequency of contact with humans. Frequent self-medication by chimpanzees in a
      high-risk environment could be a generalized adaptation to multiple parasite
      infections that respond differently to the behavior. Future parasitological
      surveys of apes and humans at Bulindi are needed for chimpanzee health monitoring
      and management, and to investigate the potential for disease transmission among
      apes, people, and domestic animals.

PMID- 22644579
TI  - Flexibility and persistence of chimpanzee (Pan troglodytes) foraging behavior in
      a captive environment.
AB  - As a result of environmental variability, animals may be confronted with
      uncertainty surrounding the presence of, or accessibility to, food resources at a
      given location or time. While individuals can rely on personal experience to
      manage this variability, the behavior of members of an individual's social group
      can also provide information regarding the availability or location of a food
      resource. The purpose of the present study was to measure how captive chimpanzees
      individually and collectively adjust their foraging strategies at an artificial
      termite mound, as the availability of resources provided by the mound varied over
      a number of weeks. As predicted, fishing activity at the mound was related to
      resource availability. However, chimpanzees continued to fish at unbaited
      locations on the days and weeks after a location had last contained food.
      Consistent with previous studies, our findings show that chimpanzees do not
      completely abandon previously learned habits despite learning individually and/or
      socially that the habit is no longer effective.

PMID- 22644580
TI  - From the mouths of monkeys: detection of Mycobacterium tuberculosis complex DNA
      from buccal swabs of synanthropic macaques.
AB  - Although the Mycobacterium tuberculosis complex (MTBC) infects a third of all
      humans, little is known regarding the prevalence of mycobacterial infection in
      nonhuman primates (NHP). For more than a century, tuberculosis has been regarded
      as a serious infectious threat to NHP species. Advances in the detection of MTBC
      open new possibilities for investigating the effects of this poorly understood
      pathogen in diverse populations of NHP. Here, we report results of a cross
      sectional study using well-described molecular methods to detect a nucleic acid
      sequence (IS6110) unique to the MTBC. Sample collection was focused on the oral
      cavity, the presumed route of transmission of MTBC. Buccal swabs were collected
      from 263 macaques representing 11 species in four Asian countries and Gibraltar.
      Contexts of contact with humans included free ranging, pets, performing monkeys,
      zoos, and monkey temples. Following DNA isolation from buccal swabs, the
      polymerase chain reaction (PCR) amplified IS6110 from 84 (31.9%) of the macaques.
      In general, prevalence of MTBC DNA was higher among NHP in countries where the
      World Health Organization reports higher prevalence of humans infected with MTBC.
      This is the first demonstration of MTBC DNA in the mouths of macaques. Further
      research is needed to establish the significance of this finding at both the
      individual and population levels. PCR of buccal samples holds promise as a method
      to elucidate the mycobacterial landscape among NHP, particularly macaques that
      thrive in areas of high human MTBC prevalence.

PMID- 22644586
TI  - Update of the pompe disease mutation database with 60 novel GAA sequence variants
      and additional studies on the functional effect of 34 previously reported
      variants.
AB  - Pompe disease is an autosomal recessive lysosomal glycogen storage disorder,
      characterized by progressive muscle weakness. Deficiency of acid alpha
      glucosidase (EC; 3.2.1.20/3) can be caused by numerous pathogenic variants in the
      GAA gene. The Pompe Disease Mutation Database at http://www.pompecenter.nl aims
      to list all variants and their effect. This update reports on 94 variants. We
      examined 35 novel and 34 known mutations by site-directed mutagenesis and
      transient expression in COS-7 cells or HEK293T cells. Each of these mutations was
      given a severity rating using a previously published system, based on the level
      of acid alpha-glucosidase activity in medium and transfected cells and on the
      quantity and quality of the different molecular mass species in the
      posttranslational modification and transport of acid alpha-glucosidase. This
      approach enabled to classify 55 missense mutations as pathogenic and 13 as likely
      nonpathogenic. Based on their nature and the use of in silico analysis (Alamut(r)
      software), 12 of the additional 25 novel mutations were predicted to be
      pathogenic including 4 splicing mutations, 6 mutations leading to frameshift, and
      2 point mutations causing stop codons. Seven of the additional mutations were
      considered nonpathogenic (4 silent and 3 occurring in intron regions), and 6 are
      still under investigation.

PMID- 22644588
TI  - Quality of life and measures of quality of life in patients with neuromuscular
      disorders.
AB  - In this review we present an overview of quality of life (QOL) and QOL measures
      in neuromuscular disorders. We discuss the characteristics of QOL measures used
      in neuromuscular research, highlighting differences between generic versus
      disease-specific and global versus health-related QOL instruments. The phenomenon
      of response shift is reviewed. Commonly used QOL instruments are reviewed for
      amyotrophic lateral sclerosis, muscle diseases, myasthenia gravis, and
      polyneuropathy. We also review some of what is known about QOL for patients with
      these neuromuscular disorders.

PMID- 22644587
TI  - Multisystemic therapy compared to telephone support for youth with poorly
      controlled diabetes: findings from a randomized controlled trial.
AB  - BACKGROUND: Few interventions have effectively improved health outcomes among
      youth with diabetes in chronic poor metabolic control. PURPOSE: This study aims
      to determine whether multisystemic therapy (MST), an intensive, home-based,
      tailored family treatment, was superior to weekly telephone support for improving
      regimen adherence and metabolic control among adolescents with chronic poor
      metabolic control. METHODS: A randomized controlled trial was conducted with 146
      adolescents with types 1 or 2 diabetes. Data were collected at baseline, 7 months
      (treatment termination), and 12 months (6 months follow-up). RESULTS: Adolescents
      receiving MST had significantly improved metabolic control at 7 (1.01 % decrease)
      and 12 months (0.74 % decrease) compared to adolescents in telephone support.
      Parents of adolescents receiving MST reported significant improvements in
      adolescent adherence. However, adolescent-reported adherence was unchanged.
      CONCLUSIONS: MST improved health outcomes among adolescents with chronic poor
      metabolic control when compared to telephone support. Home-based approaches may
      provide a viable means to improve access to behavioral interventions for such
      youth.

PMID- 22644589
TI  - Discrepancies in the P-glycoprotein-mediated transport of (18)F-MPPF: a
      pharmacokinetic study in mice and non-human primates.
AB  - PURPOSE: Several in vivo studies have found that the 5-HT(1A) PET radioligand
      (18)F-MPPF is a substrate of rodent P-glycoprotein (P-gp). However, in vitro
      assays suggest that MPPF is not a substrate of human P-gp. We have now tested the
      influence of inhibiting P-gp on the brain kinetics of (18)F-MPPF in mice and non
      human primates. METHODS: We measured the peripheral kinetics (arterial input
      function, metabolism, free fraction in plasma (f(P))) during (18)F-MPPF brain PET
      scanning in baboons with or without cyclosporine A (CsA) infusion. We measured
      (3)H-MPPF transport at the mouse BBB using in situ brain perfusion in P-gp/Bcrp
      deficient mice and after inhibiting P-gp with PSC833. RESULTS: There was an
      unexpected 1.9-fold increase in brain area under the curve in CsA-treated baboons
      (n = 4), with no change in radiometabolite-corrected arterial input. However,
      total volume of distribution corrected for f(P) (V(T)/f(P)) remained unchanged.
      In situ brain perfusion showed that P-gp restricted the permeability of the mouse
      BBB to (3)H-MPPF while Bcrp did not. CONCLUSION: These and previous in vitro
      results suggest that P-gp may not influence the permeability of human BBB to
      (18)F-MPPF. However, CsA treatment increased (18)F-MPPF free fraction, which is
      responsible for a misleading, P-gp unrelated enhanced brain uptake.

PMID- 22644590
TI  - New respirable and fast dissolving itraconazole dry powder composition for the
      treatment of invasive pulmonary aspergillosis.
AB  - PURPOSE: Novel itraconazole (ITZ)-based dry powders for inhalation (DPI) were
      optimized for aerodynamic and dissolution properties and contained excipients
      that are acceptable for inhalation. METHODS: The DPI were produced by spray
      drying solutions. The drug content, crystallinity state, and morphological
      evaluation of the dry powders were determined by high performance liquid
      chromatography, powder X-ray diffraction, differential scanning calorimetry, and
      scanning electron microscopy, respectively. A particle size analysis was
      conducted using laser light scattering. The aerodynamic behaviors of the powders
      were characterized by impaction tests. ITZ dissolution rates were evaluated using
      a dissolution method adapted to inhaled products. RESULTS: The DPI presented very
      high fine particle fractions that ranged from 46.9% to 67.0% of the nominal dose.
      The formulations showed very fast dissolution rates compared to unformulated
      crystalline ITZ with the possibility of modulating the dissolution rate by
      varying the quantity of phospholipids (PL) incorporated. ITZ remained amorphous
      while the mannitol was crystalline. The alpha, beta and delta-mannitol polymorph
      ratios varied depending on the formulation compositions. CONCLUSION: This
      formulation strategy could be an attractive alternative for treating invasive
      pulmonary aspergillosis. The ITZ and PL content are key characteristics because
      of their influence on the dissolution rate and aerosol performance.

PMID- 22644592
TI  - A conceptual model for the prediction of sexual intercourse in permanent couples.
AB  - The problem of the frequency of sexual intercourse in couples was investigated
      for the first time with a purely conceptual model. The model, based on a few
      axioms involving the notions of sexual appetite and erotic potential, was
      composed of two ordinary differential equations which turn out to be the same as
      those proposed almost one century ago in epidemiology. The model can be used to
      discuss the possibility of estimating strategic parameters from real data, as
      well as to criticize the rule of "the beans in the jar" proposed by Martin
      (1970).

PMID- 22644591
TI  - Dermal microdialysis technique to evaluate the trafficking of surface-modified
      lipid nanoparticles upon topical application.
AB  - PURPOSE: To evaluate the skin pharmacokinetics and tissue distribution of cell
      penetrating peptides (CPP) modified nano-structured lipid carrier (NLC) using an
      in vivo dermal microdialysis (MD) technique. METHODS: Celecoxib (Cxb)
      encapsulated NLCs (CXBN), CPP modified CXBN (CXBN-CPP) and Cxb-Solution (CXBS)
      formulations were prepared and tested for in vitro skin distribution. MD was used
      to assess pharmacokinetic parameters of Cxb after topical application of Cxb
      formulations. The effect of pre-treatment with Cxb formulations was evaluated for
      expression of prostaglandin-E2 (PGE(2)) and Interleukin-6 (IL-6) after exposure
      of xylene using MD. Allergic contact dermatitis (ACD) model was used to confirm
      in vivo therapeutic response of Cxb formulations. RESULTS: The cumulative
      permeation of Cxb in MD dialysate after 24 h for CXBN-CPP was significantly
      higher (p < 0.001) than CXBN and CXBS. Further, pre-treatment with CXBN-CPP
      significantly inhibited PGE(2) and IL-6 expression compared to CXBS and CXBN (p <
      0.001). In ACD model, CXBN-CPP showed significant reduction (p < 0.001) in ear
      thickness compared to controls. CONCLUSIONS: Surface modification of NLC with
      CPPs can enhance the skin permeation of Cxb and MD can be used to investigate
      pharmacokinetics of Cxb nanoparticles in the skin.

PMID- 22644593
TI  - Anthropological data regarding the adaptiveness of hebephilia.

PMID- 22644595
TI  - A sting in the tail of flexible molecules: spectroscopic and energetic challenges
      in the case of p-aminophenethylamine.
AB  - The neurotransmitter analogue p-aminophenethylamine (APEA) illustrates many of
      the pitfalls and challenges associated with spectroscopic and conformational
      analysis of flexible molecules. The combined experimental-theoretical study
      presented here resolves a long-standing controversy over its conformational
      energetic preferences. Jet-cooled resonance enhanced two-photon ionisation (R2PI)
      and IR-UV ion depletion techniques enabled conformer-specific IR spectra in the
      NH-CH stretch region to be measured for four distinct conformers of APEA.
      Comparison of spectra with theoretical calculations (including MP2, M06-2X and
      B3LYP with aug-cc-pVTZ basis sets) allows the two most populated conformers to be
      unambiguously identified as those having a gauche arrangement of the side chain,
      which facilitates an NH...pi type hydrogen bond. The other two observed
      conformers are assigned to structures with an anti-side chain. A fifth gauche
      conformer, predicted to be least stable, is not observed. Comparison with
      published conformer specific IR spectra of tyramine (Makara et al., J. Phys.
      Chem. A, 2008, 112, 13463-13469) and Raman spectra of phenylethylamine (Golan et
      al., J. Chem. Phys., 2009, 131, 024305) reveals an entirely consistent pattern of
      spectral signatures associated with the four specific conformations of the
      ethylamine side chain evident in APEA, and aids assignment of the associated CH
      and NH stretch fundamentals, some of which have very weak IR intensities.
      Extensive calculations of the relative energetic trends of the five conformers
      have been carried out. In comparison to the highest level of theory considered,
      CCSD(T)-F12b/cc-pVDZ-F12, MP2 overestimate the energy difference, whereas DFT
      significantly underestimates the energetic preference for NH...pi stabilised
      gauche conformers, although inclusion of dispersion (M06-2X, B3LYP-D3) improves
      the DFT results.

PMID- 22644596
TI  - Infant-directed communication in lowland gorillas (Gorilla gorilla): do older
      animals scaffold communicative competence in infants?
AB  - Infant-directed speech is a linguistic phenomenon in which adults adapt their
      language when addressing infants in order to provide them with more salient
      linguistic information and aid them in language acquisition. Adult-directed
      language differs from infant-directed language in various aspects, including
      speech acoustics, syntax, and semantics. The existence of a "gestural motherese"
      in interaction with infants, demonstrates that not only spoken language but also
      nonvocal modes of communication can become adapted when infants are recipients.
      Rhesus macaques are so far the only nonhuman primates where a similar phenomenon
      to "motherese" has been discovered: the acoustic spectrum of a particular
      vocalization of adult females may be altered when the addressees are infants. The
      present paper describes how gorillas adjust their communicative strategies when
      directing intentional, nonvocal play signals at infants in the sense of a
      "nonvocal motherese." Animals of ages above infancy use a higher rate of
      repetitions and sequences of the tactile sensory modality when negotiating play
      with infants. This indicates that gorillas employ a strategy of infant-specific
      communication.

PMID- 22644597
TI  - Hospital discharge database optimization in Guillain-Barre syndrome surveillance.
AB  - INTRODUCTION: Precise causes and risk factors for Guillain-Barre syndrome (GBS)
      remain incompletely understood, and monitoring its incidence remains important in
      public health. Active surveillance is not sustainable, but hospital discharge
      databases (HDDs) may be suitable for passive surveillance. METHODS: We optimized
      Tennessee's HDD of all ICD-9 codes of 357.0, from 2000 to 2010. Discharges for
      persons with a GBS diagnosis in a previous hospitalization in the database were
      excluded. HDD results were compared with the CDC's active surveillance program
      during the H1N1 vaccination program of 2009-2010. RESULTS: Of 2,659 records of
      Tennessee residents initially identified, 1077 (40%) had prior diagnoses of GBS.
      Adjusted annual rates ranged from 1.24 to 1.57 per 100,000 population. The
      sensitivity of the optimized HDD was 0.81 with a positive predictive value of
      0.45. CONCLUSIONS: Optimization of a HDD through exclusion of nonacute cases
      results in an acceptable and practical database for passive surveillance of GBS.

PMID- 22644598
TI  - Acute compartment syndrome: obtaining diagnosis, providing treatment, and
      minimizing medicolegal risk.
AB  - Acute compartment syndrome (ACS) is a surgical emergency. Diagnosis depends on a
      high clinical suspicion and an understanding of risk factors, pathophysiology and
      subtle physical exam findings. The typical high risk scenario for ACS is a male
      patient younger than 35 years of age, involved in a high energy sport or roadway
      collision, resulting in a tibial shaft fracture. He will go on to develop acute
      compartment syndrome of the leg in less than 10 hours and require emergent
      fasciotomy. Diagnosis of ACS in this patient is primarily a clinical one but can
      be confirmed with invasive intracompartmental pressure monitoring or non-invasive
      near infrared spectroscopy (NIRS). Delaying the diagnosis will likely result in
      some degree of permanent disability and places the surgeon at high risk for
      litigation. This article reviews the salient features of acute compartment
      syndrome that should be understood by all orthopaedic residents and surgeons.

PMID- 22644599
TI  - Proximal humerus fractures.
AB  - Proximal humeral fractures are extremely common injuries, and are one of the true
      osteoporotic fractures. Most fractures can be effectively treated nonoperatively,
      as the rich vascularity and broad cancellous surfaces impart a high propensity
      for healing. Additionally, many fracture patterns result in adequate bone contact
      and minimal displacement with acceptable alignment. Open reduction and internal
      fixation of displaced fractures can improve outcomes, depending on the pre-injury
      functional status of the patient. If operative treatment is selected, unique
      treatment challenges must be overcome, including obtaining and maintaining
      reduction of small bone fragments with strong muscle forces, often in
      osteoporotic bone. Many options are feasible, including plates, nails, sutures,
      and other novel devices. Locking plates are the most common device used, but
      technical detail is critical to minimize the risk of implant failure, loss of
      reduction, and reoperation.

PMID- 22644600
TI  - Storage and disposal of unused medications: knowledge, behavior, and attitudes
      among Serbian people.
AB  - BACKGROUND: Improper disposal of medications potentially poses a significant
      environmental risk and storage of expired and unused medications in households
      provides an increased risk of accidental childhood poisonings. OBJECTIVE: The
      objective of this study was to investigate the storage and disposal habits of
      medications amongst the population in the South Backa District of Serbia, and to
      gain insight into the attitudes and knowledge of the population about the proper
      disposal of medications. Setting Households in South Backa District. METHOD: The
      study was conducted during the 6-month period from February 2010 to July 2010 and
      involved a random sample of households. The questionnaire-based study was
      performed by a trained interviewer. MAIN OUTCOME MEASURE: number of expired and
      unused medications in families, behavior and knowledge about the disposal of
      medications. RESULTS: Of 230 families, 208 (108 urban and 100 rural) agreed to
      participate and complete the questionnaire(90 % response rate). The drugs were
      mostly kept in a specific place-home pharmacy (89.8 % [urban] and 89.0 %
      [rural]). Exposure of children to medications in the home environment was similar
      in urban and rural families (19.6 % [urban] and 23.1 % [rural]). The frequency of
      expired medications was not observed to be different between the urban and rural
      households (10.3 % [urban] and 11.8 % [rural]). The most common method for
      disposal of household medications is disposal in the garbage (85.6 % [urban] and
      74.5 % [rural]) or in the toilet (8.7 % [urban] and 6.4 % [rural]). However,
      inconsistent with disposal practices, half of the urban and rural participants
      thought that throwing medications in the garbage, toilet, or sink has a
      detrimental effect on the environment. CONCLUSION: Public services in Serbia,
      including government and health sectors, need to be more proactive about
      educating people on how to store and dispose medications, as well as finding a
      way for implementation of the law on medications wastage destruction.

PMID- 22644601
TI  - Primary closure versus T-tube drainage in laparoscopic common bile duct
      exploration: a meta-analysis of randomized clinical trials.
AB  - PURPOSE: To compare the safety and effectiveness of primary closure with those of
      T-tube drainage in laparoscopic common bile duct exploration (LCBDE) for
      choledocholithiasis. METHODS: A comprehensive search was performed in the PubMed,
      EmBase, and Cochrane Library databases. Only randomized controlled trials
      comparing primary closure with T-tube drainage in LCBDE were considered eligible
      for this meta-analysis. The analyzed outcome variables included postoperative
      mortality, overall morbidity, biliary complication rate, biliary leak rate,
      reoperation, operating time, postoperative hospital stay, time to abdominal drain
      removal, and retained stone. All calculations and statistical tests were
      performed using ReviewerManager 5.1.2 software. RESULTS: A total of 295 patients
      (148 patients with primary closure and 147 patients with T-tube drainage) from
      three trials were identified and analyzed. No deaths occurred in any of the
      trials. Primary closure showed significantly better results in terms of morbidity
      (risk ratio (RR), 0.51; 95% confidence interval (CI), 0.30 to 0.88), biliary
      complication without a combination of retained stone (RR, 0.44; 95% CI, 0.20 to
      0.97), reoperation (RR, 0.16; 95% CI, 0.03 to 0.87), operating time (mean
      difference (MD), -20.72; 95% CI, -29.59 to -11.85), postoperative hospital stay
      (MD, -3.24; 95% CI, -3.96 to -2.52), and time to abdominal drainage removal (MD, 
      0.45; 95% CI, -0.86 to -0.04). Statistically significant differences were not
      found between the two methods in terms of biliary leak, biliary complication, and
      retained stones. CONCLUSION: The current meta-analysis indicates that primary
      closure of the common bile duct is safer and more effective than T-tube drainage
      for LCBDE. Therefore, we do not recommend routine performance of T-tube drainage
      in LCBDE.

PMID- 22644602
TI  - Minimally invasive surgical treatment of sigmoid diverticulitis.
AB  - INTRODUCTION: Diverticular disease is very common in Western societies. However,
      there is a trend towards reducing indications for the surgical management of
      diverticulitis. Minimally invasive surgery offers many potential advantages to
      patients in the treatment of diverticulitis and may optimise surgical
      indications. METHODS: A systematic literature review of minimally invasive
      techniques was carried out for the treatment of diverticulitis. The following
      techniques were reviewed: laparoscopic, single-port, natural orifice specimen
      extraction, natural orifice transluminal endoscopic surgery and laparoscopic
      lavage for the treatment of diverticulitis. RESULTS: In total, 2,050 minimally
      invasive cases were reviewed. Of all the different minimally invasive techniques
      published regarding the management of diverticular disease, laparoscopic surgery
      is the only technique that has undergone the rigours of randomised controlled
      trials. The documented benefits are less blood loss, less pain and analgesic
      requirements, a reduction in major complications, a reduction in the frequency of
      drain usage, a reduction in the duration of postoperative ileus and shorter
      hospital stay. However, operative time does appear to be longer. It has also been
      demonstrated that elective laparoscopic surgery results in improved quality of
      life and social functioning. CONCLUSION: Minimally invasive surgery for the
      treatment of diverticular disease appears feasible and safe. The result of future
      randomised trials will more clearly define the role each minimally invasive
      technique will play in the future.

PMID- 22644603
TI  - Natural disease course and genotype-phenotype correlations in Complex I
      deficiency caused by nuclear gene defects: what we learned from 130 cases.
AB  - Mitochondrial complex I is the largest multi-protein enzyme complex of the
      oxidative phosphorylation system. Seven subunits of this complex are encoded by
      the mitochondrial and the remainder by the nuclear genome. We review the natural
      disease course and signs and symptoms of 130 patients (four new cases and 126
      from literature) with mutations in nuclear genes encoding structural complex I
      proteins or those involved in its assembly. Complex I deficiency caused by a
      nuclear gene defect is usually a non-dysmorphic syndrome, characterized by severe
      multi-system organ involvement and a poor prognosis. Age at presentation may
      vary, but is generally within the first year of life. The most prevalent symptoms
      include hypotonia, nystagmus, respiratory abnormalities, pyramidal signs,
      dystonia, psychomotor retardation or regression, failure to thrive, and feeding
      problems. Characteristic symptoms include brainstem involvement, optic atrophy
      and Leigh syndrome on MRI, either or not in combination with internal organ
      involvement and lactic acidemia. Virtually all children ultimately develop Leigh
      syndrome or leukoencephalopathy. Twenty-five percent of the patients died before
      the age of six months, more than half before the age of two and 75 % before the
      age of ten years. Some patients showed recovery of certain skills or are still
      alive in their thirties . No clinical, biochemical, or genetic parameters
      indicating longer survival were found. No clear genotype-phenotype correlations
      were observed, however defects in some genes seem to be associated with a better
      or poorer prognosis, cardiomyopathy, Leigh syndrome or brainstem lesions.

PMID- 22644604
TI  - Creatine metabolism in urea cycle defects.
AB  - Creatine (Cr) and phosphocreatine play an essential role in energy storage and
      transmission. Maintenance of creatine pool is provided by the diet and by de novo
      synthesis, which utilizes arginine, glycine and s-adenosylmethionine as
      substrates. Three primary Cr deficiencies exists: arginine:glycine
      amidinotransferase deficiency, guanidinoacetate methyltransferase deficiency and
      the defect of Cr transporter SLC6A8. Secondary Cr deficiency is characteristic of
      ornithine-aminotransferase deficiency, whereas non-uniform Cr abnormalities have
      anecdotally been reported in patients with urea cycle defects (UCDs), a disease
      category related to arginine metabolism in which Cr must be acquired by de novo
      synthesis because of low dietary intake. To evaluate the relationships between
      ureagenesis and Cr synthesis, we systematically measured plasma Cr in a large
      series of UCD patients (i.e., OTC, ASS, ASL deficiencies, HHH syndrome and
      lysinuric protein intolerance). Plasma Cr concentrations in UCDs followed two
      different trends: patients with OTC and ASS deficiencies and HHH syndrome
      presented a significant Cr decrease, whereas in ASL deficiency and lysinuric
      protein intolerance Cr levels were significantly increased (23.5 vs. 82.6
      MUmol/L; p < 0.0001). This trend distribution appears to be regulated upon
      cellular arginine availability, highlighting its crucial role for both
      ureagenesis and Cr synthesis. Although decreased Cr contributes to the
      neurological symptoms in primary Cr deficiencies, still remains to be explored if
      an altered Cr metabolism may participate to CNS dysfunction also in patients with
      UCDs. Since arginine in most UCDs becomes a semi-essential aminoacid, measuring
      plasma Cr concentrations might be of help to optimize the dose of arginine
      substitution.

PMID- 22644605
TI  - Functional and electrophysiological characterization of four non-truncating
      mutations responsible for creatine transporter (SLC6A8) deficiency syndrome.
AB  - Intellectual disability coupled with epilepsy are clinical hallmarks of the
      creatine (Cr) transporter deficiency syndrome resulting from mutations in the
      SLC6A8 gene. So far characterization of pathogenic mutations of SLC6A8 has been
      limited to Cr uptake. The aim of our study was to characterize the electrogenic
      and pharmacological properties of non truncating SLC6A8 mutations identified in
      patients presenting variable clinical severity. Electrophysiological and
      pharmacological properties of four mutants (including two novel ones) were
      studied in X. laevis oocyte expression system. Creatine uptake was assessed with
      [(14)C]-Cr in X. laevis and patients' fibroblasts. Subcellular localization was
      determined by immunofluorescence and western blot. All mutants were properly
      targeted to the plasma membrane in both systems. Mutations led to the complete
      loss of both electrogenic and transport activities in X. laevis and Cr uptake in
      patients' fibroblasts. Among the Cr analogs tested, guanidinopropionate induced
      an electrogenic activity with the normal SLC6A8 transporter similar to creatine
      whereas a phosphocreatine derivative, PCr-Mg-CPLX, resulted in partial activity.
      SLC6A8 mutants displayed no electrogenic activity with all Cr analogs tested in
      X. laevis oocytes. Although the mutations altered various domains of SLC6A8 Cr
      uptake and electrogenic properties were completely inhibited and could not be
      dissociated. Besides the metabolic functions of Cr, the loss of SLC6A8
      electrogenic activity, demonstrated here for the first time, may also play a role
      in the altered brain functions of the patients.

PMID- 22644614
TI  - Acute myeloid leukemia with mediastinal myeloid sarcoma refractory to acute
      myeloid leukemia therapy but responsive to L-asparaginase.
AB  - We report the case of a 14-year-old female with acute myeloid leukemia (AML) and
      myeloid sarcomas (MS) in the anterior mediastinum and around numerous bones.
      Laboratory tests showed a white blood cell count of 4.0 * 10(9)/l with 7.0 %
      blasts. Computed tomography revealed a mediastinal mass and pleural effusion;
      pleural effusion cytology was negative for malignant cells. In addition,
      disseminated intravascular coagulation (DIC) was present. Following DIC therapy,
      thoracoscopic and bone marrow biopsies were performed. Immunostaining and surface
      marker analysis revealed that the blast cells were positive for cytoplasmic
      myeloperoxidase, CD4, CD7, CD33, CD44, CD117, and HLA-DR, but negative for CD34
      and CD56. Karyotype was normal. MS associated with AML was diagnosed. Multidrug
      chemotherapy for AML was completely ineffective, and MS continued to progress.
      Immunohistochemistry revealed that the blasts were negative for asparagine
      synthetase (AS); therefore, chemotherapy including L: -asparaginase was
      initiated. After the first administration of L: -asparaginase, the patient's
      condition improved; however, she subsequently developed tumor lysis syndrome and
      sepsis, which eventually led to death. Aggressive MS in childhood is rare and
      refractory to existing AML chemotherapy. Chemotherapy including L: -asparaginase
      may prove to be effective in such cases, especially those in which blast cells
      show negative AS expression.

PMID- 22644615
TI  - Activation of oral trigeminal neurons by fatty acids is dependent upon
      intracellular calcium.
AB  - The chemoreception of dietary fat in the oral cavity has largely been attributed
      to activation of the somatosensory system that conveys the textural properties of
      fat. However, the ability of fatty acids, which are believed to represent the
      proximate stimulus for fat taste, to stimulate rat trigeminal neurons has
      remained unexplored. Here, we found that several free fatty acids are capable of
      activating trigeminal neurons with different kinetics. Further, a polyunsaturated
      fatty acid, linoleic acid (LA), activates trigeminal neurons by increasing
      intracellular calcium concentration and generating depolarizing receptor
      potentials. Ion substitution and pharmacological approaches reveal that
      intracellular calcium store depletion is crucial for LA-induced signaling in a
      subset of trigeminal neurons. Using pseudorabies virus (PrV) as a live cell
      tracer, we identified a subset of lingual nerve-innervated trigeminal neurons
      that respond to different subsets of fatty acids. Quantitative real-time PCR of
      several transient receptor potential channel markers in individual neurons
      validated that PrV labeled a subset but not the entire population of lingual
      innervated trigeminal neurons. We further confirmed that the LA-induced
      intracellular calcium rise is exclusively coming from the release of calcium
      stores from the endoplasmic reticulum in this subset of lingual nerve-innervated
      trigeminal neurons.

PMID- 22644616
TI  - RUNX1T1, a chromatin repression protein, is a candidate gene for autosomal
      dominant intellectual disability.

PMID- 22644617
TI  - Brief report: pointing cues facilitate word learning in children with autism
      spectrum disorder.
AB  - Children with autism spectrum disorder (ASD) reportedly have difficulty
      associating novel words to an object via the speaker's gaze. It has also been
      suggested that their performance is related to their gaze duration on the object
      and improves when the object moves and becomes more salient. However, there is a
      possibility that they have only relied on the object's movement and have not
      referenced the speaker's cue (i.e. gaze direction). The current study with
      children with ASD and typically developing children aged 6-11 years demonstrated
      that adding another speaker's cue (i.e. pointing) improves the performance of
      children with ASD. This suggests that additional speaker's cues may help
      referential word learning in children with ASD.

PMID- 22644618
TI  - Sleep duration, spot urinary 6-sulfatoxymelatonin levels and risk of breast
      cancer among Chinese women in Singapore.
AB  - We previously reported an inverse association between sleep duration and breast
      cancer risk in the prospective, population-based Singapore Chinese Health Study
      (SCHS) cohort (Wu et al., Carcinogenesis 2008;29:1244-8). Sleep duration was
      significantly positively associated with 6-sulfatoxymelatonin (aMT6s) levels
      determined in a spot urine, but aMT6s levels in breast cancer cases were lacking
      (Wu et al., Carcinogenesis 2008;29:1244-8). We updated the sleep duration-breast
      cancer association with 14 years of follow-up of 34,028 women in the SCHS. In a
      nested case-control study conducted within the SCHS, randomly timed,
      prediagnostic urinary aMT6s concentrations were compared between 248 incident
      breast cancer and 743 individually matched cohort controls. Three female controls
      were individually matched to each case on age at baseline interview (within 3
      years), dialect group, menopausal status, date of baseline interview (within 2
      years), date of urine sample collection (within 6 months) and timing of urine
      collection during the day (within 1 hr). Cox proportional hazards and conditional
      regression models with appropriate adjustment for confounders were used to
      examine the sleep- and aMT6s-breast cancer relationships. Breast cancer risk was
      not significantly associated with sleep duration; adjusted odds ratio (OR) for 9+
      vs. <= 6 hr is 0.89 [95% confidence interval (95% CI) = 0.64-1.22]. Prediagnostic
      aMT6s levels did not differ between breast cancer cases and matched controls;
      adjusted OR for highest versus lowest quartiles is 1.00 (95% CI = 0.64-1.54). We
      conclude that sleep duration is not significantly associated with breast cancer
      risk reduction. Melatonin levels derived from randomly timed spot urine are
      unrelated to breast cancer. Randomly timed, spot urine-derived melatonin levels
      are noninformative as surrogates of nocturnal melatonin production.

PMID- 22644619
TI  - Controlling nanostructures of mesoporous silica fibers by supramolecular assembly
      of genetically modifiable bacteriophages.
AB  - A useful virus: The synthesis of a new family of mesoporous silica fibers is
      reported. Monodisperse filamentous bacteriophages self-assembled into highly
      ordered hexagonal lattices that were used as templates for the formation of
      silica nanostructures. Removal of the bacteriophage assembly through calcination
      led to the formation of mesoporous silica fibers with pore structures precisely
      defined by the bacteriophage assembly (see picture).

PMID- 22644620
TI  - Pressure-driven orbital reorientations and coordination-sphere reconstructions in
      [CuF2(H2O)2(pyz)].

PMID- 22644621
TI  - Analysis of the regulatory and catalytic domains of PTEN-induced kinase-1
      (PINK1).
AB  - Mutations of the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1)
      gene can cause early-onset familial Parkinson disease (PD). PINK1 encodes a
      neuroprotective protein kinase localized at the mitochondria, and its involvement
      in regulating mitochondrial dynamics, trafficking, structure, and function is
      well documented. Owing to the lack of information on structure and biochemical
      properties for PINK1, exactly how PINK1 exerts its neuroprotective function and
      how the PD-causative mutations impact on PINK1 structure and function remain
      unclear. As an approach to address these questions, we conducted bioinformatic
      analyses of the mitochondrial targeting, the transmembrane, and kinase domains of
      PINK1 to predict the motifs governing its regulation and function. Our report
      sheds light on how PINK1 is targeted to the mitochondria and how PINK1 is cleaved
      by mitochondrial peptidases. Moreover, it includes a potential optimal
      phosphorylation sequence preferred by the PINK1 kinase domain. On the basis of
      the results of our analyses, we predict how the PD-causative mutations affect
      processing of PINK1 in the mitochondria, PINK1 kinase activity, and substrate
      specificity. In summary, our results provide a conceptual framework for future
      investigation of the structural and biochemical basis of regulation and the
      neuroprotective mechanism of PINK1.

PMID- 22644622
TI  - Preservation versus division of ilioinguinal nerve on open mesh repair of
      inguinal hernia: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Chronic groin pain after inguinal hernia repair, a serious problem,
      is caused by entrapment of the ilioinguinal nerve either by mesh or development
      of fibrosis. Division of the ilioinguinal nerve during hernioplasty has been
      found to reduce the incidence of chronic groin pain. However, the traditional
      approach favors preservation of the ilioinguinal nerve during open hernia repair.
      METHODS: We conducted a systematic review and meta-analysis of randomized
      controlled trials that compared the outcomes of preservation versus division of
      the ilioinguinal nerve during open mesh repair of inguinal hernia. The primary
      outcome was the incidence of groin pain; secondary outcomes were numbness and
      sensory loss. RESULTS: We reviewed six trials with 1,286 patients. We found no
      difference between the groups for the incidence of groin pain or numbness at 1,
      6, and 12 months after open mesh inguinal repair. The incidence of sensory loss
      or change was significantly higher in the division group than in the preservation
      group at 6 months [risk ratio (RR) 1.25; 95 % confidence interval (CI) 1.02-1.53]
      and at 12 months (RR 1.55; 95 % CI 1.01-2.37) postoperatively. No significant
      differences between the groups were noted at any other points in time.
      CONCLUSIONS: Preservation of the ilioinguinal nerve during open mesh repair of
      inguinal hernia is associated with a decreased incidence of sensory loss at 6 and
      12 months postoperatively compared with that of the division technique. No
      significant differences were found between the groups for chronic groin pain or
      numbness.

PMID- 22644623
TI  - Protective effect of rat pancreatic progenitors cells expressing Pdx1 and nestin
      on islets survival and function in vitro and in vivo.
AB  - To maintain islets survival and function is critical in successful pancreatic
      transplantation. Pancreatic progenitors cells (PPCs) with lineage potentials,
      giving rise to exocrine, endocrine, and duct cells, reside in developing and
      adult pancreas. As tissue-specific stem cells, they can produce pancreatic tissue
      specific matrix factors to promote islets survival and function. The aim of our
      research was to investigate the protective effect of rat pancreatic-duodenal
      homeobox 1 (Pdx1)(+)/nestin(+) PPCs on islets. In vitro, co-culturing islets with
      Pdx1(+)/nestin(+) PPCs prolonged the former survival from 7 to 14 days.
      Furthermore, with high glucose (300.8 mg/dl) stimuli, the yield of insulin in co
      cultures was significantly higher than that in control group (single islets
      group). In vivo, co-transplanting islets and Pdx1(+)/nestin(+) PPCs for 3 days,
      the blood glucose of diabetic rat was significantly decreased to normal level and
      sustained for 2 weeks. Without Pdx1(+)/nestin(+) PPCs in islets transplantation,
      hyperglycemia was reversed at day 7 and recovered at day 15. Pathology analysis
      showed that islets had remnants in co-transplantation at day 21, as complete
      graft rejection in alone islets transplantation. Our study showed that
      Pdx1(+)/nestin(+) PPCs displayed the ability of preserving islets viability and
      function in vitro and prolonging their survival in vivo.

PMID- 22644624
TI  - Depot-specific regulation of autotaxin with obesity in human adipose tissue.
AB  - Autotaxin (ATX) is a lysophospholipase D involved in synthesis of a bioactive
      mediator: lysophosphatidic. ATX is abundantly produced by adipocytes and exerts a
      negative action on adipose tissue expansion. In both mice and humans, ATX
      expression increases with obesity in association with insulin resistance. In the
      present study, fat depot-specific regulation of ATX was explored in human. ATX
      mRNA expression was quantified in visceral and subcutaneous adipose tissue in
      obese (BMI > 40 kg/m(2); n = 27) and non-obese patients (BMI < 25 kg/m(2); n =
      10). Whatever the weight status of the patients is, ATX expression was always
      higher (1.3- to 6-fold) in subcutaneous than in visceral fat. Nevertheless,
      visceral fat ATX was significantly higher (42 %) in obese than in non-obese
      patients, whereas subcutaneous fat ATX remained unchanged. In obese patients,
      visceral fat ATX expression was positively correlated with diastolic arterial
      blood pressure (r = 0.67; P = 0.001). This correlation was not observed with
      subcutaneous fat ATX. Visceral fat ATX was mainly correlated with leptin (r =
      0.60; P = 0.001), inducible nitric oxide synthase (r = 0.58; P = 0,007), and
      apelin receptor (r = 0.50; P = 0.007). These correlations were not observed with
      subcutaneous fat ATX. These results reveal that obesity-associated upregulation
      of human adipose tissue ATX is specific to the visceral fat depot.

PMID- 22644625
TI  - Iterative estimation of coherent-scattering profiles from given positions by use
      of a single-direction beam.
AB  - The coherent-scattering distribution is useful for characterization of materials
      in the medical field, and obtaining this information from a given position in the
      object is a useful new diagnostic approach. We propose a simpler geometric
      approach, which requires only a single-direction X-ray beam with no collimator in
      front of the detector. This method iteratively estimates coherent-scattering
      profiles from given positions along the beam path, based on the projections
      positioned at different object-to-detector distances. We confirmed the proposed
      calculation algorithm by numerical simulation and performed a simple experiment
      including attenuation correction. The accuracy of matching with the original
      profiles was dependent on the number of iterations, the distance between the
      first and second detectors, the distance between two objects, and the shape of
      the scattering profile. Whereas multiple scattering was the main problem in the
      experiment, the calculated scattering profiles matched well with the original
      profile. This technique indicates the feasibility of developing a coherent
      scatter imaging system.

PMID- 22644631
TI  - Cyclical parthenogenesis and viviparity in aphids as evolutionary novelties.
AB  - Evolutionary novelties represent challenges to biologists, particularly those who
      would like to understand the developmental and genetic changes responsible for
      their appearance. Most modern aphids possess two apparent evolutionary novelties:
      cyclical parthenogenesis (a life cycle with both sexual and asexual phases) and
      viviparity (internal development and live birth of progeny) in their asexual
      phase. Here I discuss the evolution of these apparent novelties from a
      developmental standpoint. Although a full understanding of the evolution of
      cyclical parthenogenesis and viviparity in aphids can seem a daunting task, these
      complex transitions can at least be broken down into a handful of steps. I argue
      that these should include the following: a differentiation of two developmentally
      distinct oocytes; de novo synthesis of centrosomes and modification of meiosis
      during asexual oogenesis; a loss or bypass of any cell cycle arrest and changes
      in key developmental events during viviparous oogenesis; and a change in how
      mothers specify the sexual vs. asexual fates of their progeny. Grappling with the
      nature of such steps and the order in which they occurred ought to increase our
      understanding and reduce the apparent novelty of complex evolutionary
      transitions.

PMID- 22644632
TI  - Contributing factors for the incidence of aneuploidy in older patients undergoing
      intracytoplasmic sperm injection cycles.
AB  - PURPOSE: To evaluate different factors that might affect the incidence of embryo
      aneuploidy in intracytoplasmic sperm injection cycles (ICSI). METHODS: One
      hundred and ninety ICSI cycles in conjunction with preimplantation genetic
      screening (PGS) were included. The influence of the following variables on the
      aneuploidy incidence was evaluated: (i) maternal and (ii) paternal ages, (iii)
      dose of FSH administered, (iv) dose of FSH per number of retrieved matured
      oocytes (FSH/MII), (v) serum 17beta-oestradiol levels on the ovulation trigger
      day, (vi) aspirated follicles and (vii) retrieved oocytes. RESULTS: A total of
      440 embryos were successfully biopsied, of which 240 were considered euploid and
      200 were considered aneuploid. The paternal age (Slope: 0.2, p = 0.372), total
      dose of FSH (Slope: 0.2, p = 0.218), FSH/MII (Slope: 0.1, p = 0.296) and 17beta
      oestradiol levels (Slope: 0.2, p = 0.378) were not correlated with the presence
      of aneuploidy. However, the maternal age (Slope: 1.7, p < 0.01), aspirated
      follicles (Slope: 1.9, p < 0.01) and retrieved oocytes (Slope: 2.6, p < 0.01)
      were negatively correlated with the incidence of aneuploidy. CONCLUSIONS: Even in
      older patients, lower oocyte yields may represent a more appropriate response to
      ovarian stimulation, allowing the most competent follicles and oocytes to develop
      and thereby reducing the occurrence of embryo aneuploidy.

PMID- 22644633
TI  - The effect of immature oocytes quantity on the rates of oocytes maturity and
      morphology, fertilization, and embryo development in ICSI cycles.
AB  - PURPOSE: The goal was to evaluate the role of the number of retrieved immature
      oocytes on mature oocyte counts and morphology, and also the rates of
      fertilization and embryo development in ICSI cycles. METHODS: 101 ICSI cycles
      were included in this prospective evaluation. Patients were divided into 2 groups
      of A (<= 2 immature oocytes) and B (> 2 immature oocytes). In sub-analysis, the
      impacts of the number of GV and MI oocytes were assessed on the rates of
      fertilization and embryo development. Also, correlations between the numbers of
      immature and mature oocytes, as well as maternal age between two groups were
      analyzed. Assessments of oocyte morphology, fertilization, embryo quality and
      development were done accordingly. RESULTS: There was no correlation between the
      immature oocytes quantity with the number of mature ones. There were
      insignificant differences for embryo development between two groups, but
      fertilization rate was higher in group A (P = 0.03). In sub-analysis,
      insignificant differences were observed between two groups of <= and >2 GV and MI
      oocytes for rates of fertilization and embryo development. Also, the rates of
      clinical pregnancy and delivery were insignificant between groups. The rate of
      morphologically abnormal oocytes had no significant difference between two
      groups, except for wide perivitelline space (PVS) which was higher in group A (P
      = 0.03). There was no significant difference for maternal age between two groups.
      CONCLUSIONS: In cases with few retrieved immature oocytes, rates of fertilization
      and incidence of wide PVS may increase, although immature oocytes may not have
      any negative impacts on early embryo development, or the rates on number of
      mature oocytes.

PMID- 22644634
TI  - Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced
      hypertension in Chinese population: a meta-analysis.
AB  - PURPOSE: There have been many studies concerning the associations of angiotensin
      converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T polymorphisms with
      pregnancy induced hypertension (PIH) among Chinese populations. However, the
      results were inconsistent, prompting the necessity of meta-analysis. METHODS:
      Studies published in English and Chinese were mainly searched in EMbase, PubMed
      and CBM up to January 2012. RESULTS: Twenty-three studies with 3,551 subjects for
      ACE I/D and seven studies with 1,296 subjects for AGT M235T were included.
      Significant associations were found between ACE I/D and PIH under dominant,
      recessive and allelic models. A separate analysis confined to preeclampsia
      suggested that ACE I/D was associated with preeclampsia under recessive model and
      allelic model, but not dominant model. Stratified analyses were conducted as meta
      regression analysis indicated that the sample size of case group was a
      significant source of heterogeneity, which suggested no significant association
      between ACE I/D and PIH in the subgroup of more than 100 cases. Associations were
      found between AGT M235T and PIH under dominant genetic model (OR = 1.59; 95 %CI:
      1.04-2.42), recessive genetic model (OR = 1.60; 95 %CI: 1.07-2.40), and allelic
      model (OR = 1.40; 95 %CI: 1.17-1.68). No publication bias was found in either
      meta-analysis. CONCLUSIONS: The present meta-analysis suggested significant
      associations between ACE I/D, AGT M235T and PIH in Chinese populations. However,
      no significant association was found between ACE I/D and PIH in the subgroup of
      more than 100 cases. Studies with larger sample sizes are necessary to
      investigate the associations between gene polymorphisms and PIH in Chinese
      populations.

PMID- 22644635
TI  - Does mtDNA copy number mean mitochondrial abundance?

PMID- 22644636
TI  - Outcome of in vitro fertilization in patients with proven poor ovarian
      responsiveness after early vs. mid-follicular LH exposure: a prospective,
      randomized, controlled study.
AB  - OBJECTIVE: To compare early vs. mid-follicular exposure to LH in patients with
      poor ovarian responsiveness undergoing in vitro fertilization (IVF). DESIGN:
      Prospective, randomized, controlled trial. SETTING: University Hospital,
      University-affiliated private Clinic. PATIENTS: Five hundred-thirty women with
      poor ovarian responsiveness during the first IVF cycle, undergoing their second
      IVF attempt. INTERVENTIONS: In a GnRH-analogue long protocol, ovarian stimulation
      with recombinant FSH (300 IU/day) plus randomly assigned addition of recombinant
      LH (150 IU/day) from day 1 (early LH exposure; n = 264) or from day 7 (late LH
      exposure; n = 266). MAIN OUTCOME MEASURE(S): Primary outcome was the number of
      oocytes retrieved. Secondary outcomes were: cancellation rate, total gonadotropin
      dose, duration of ovarian stimulation, number of embryos available for transfer,
      pregnancy rate per started cycle, per OPU and per embryo transfer, implantation
      rate, delivered/ongoing pregnancy rate. RESULTS: Apart from the totally
      administered LH dose, that was significantly higher in the group receiving it
      from day 1, all parameters related to IVF outcome were non significantly
      different in the two groups. CONCLUSIONS: Adding LH to FSH from day 1 or from day
      7 of ovarian stimulation in a GnRH-agonist long protocol exerts comparable
      effects on IVF outcome in poor responders.

PMID- 22644639
TI  - Bioactive compounds extracted from Ecklonia cava by using enzymatic hydrolysis
      protects high glucose-induced damage in INS-1 pancreatic beta-cells.
AB  - Pancreatic beta-cells are very sensitive to oxidative stress and this might play
      an important role in beta-cell death in diabetes. In the present study, we
      investigated whether the brown alga Ecklonia cava has protective effects against
      high glucose-induced damage in INS-1 pancreatic beta-cells. For that purpose, we
      prepared an enzymatic hydrolysate from E. cava (EHE) by using the carbohydrase,
      Celluclast. High-glucose (30 mM) treatment induced glucotoxicity, whereas EHE
      prevented cells from high glucose-induced damage then restoring cell viability
      was significantly increased. Furthermore, lipid peroxidation, intracellular
      reactive oxygen species (ROS) and nitric oxide (NO) were overproduced as the
      result of the treatment by high glucose; however, these lipid peroxidation, ROS
      and NO generations were effectively inhibited by addition of EHE in a dose
      dependent manner. Moreover, EHE treatment increased activities of antioxidant
      enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione
      peroxidase (GSH-px) in high glucose pretreated INS-1 pancreatic beta-cells. EHE
      slightly reduced the expression of pro-apoptotic protein Bax induced by high
      glucose but increased the expression of Bcl-2, an anti-apoptotic protein. These
      findings indicate that EHE might be used as potential nutraceutical agent which
      will protect the glucotoxicity caused by hyperglycemia-induced oxidative stress
      associated with diabetes.

PMID- 22644638
TI  - PAX7+ satellite cells in young and older adults following resistance exercise.
AB  - INTRODUCTION: Resistance exercise (RE) stimulates a muscle protein anabolic
      response partially through enhanced satellite cell (SC) activity, however, age-
      and gender-related changes in SC content over a 24-h time course are not known.
      METHODS: Ten young (27 +/- 2 years) men and women and 11 older (70 +/- 2 years)
      men and women performed an acute bout of RE. Myofiber and SC characteristics were
      determined from muscle biopsies of the vastus lateralis using
      immunohistochemistry. Immunoblotting was used to determine phosphorylation of
      cyclin-dependent kinase-2 and protein expression of p27(Kip1) and cyclin D1.
      RESULTS: Pax7+ SC were significantly increased in young men 24 h following RE.
      Percent SC were significantly increased in older women at 6 and 24 h following
      RE. Aging decreased myonuclear domain and increased protein expression of
      p27(Kip1) . CONCLUSIONS: An acute bout of RE increases SC content in young men at
      24 h and older women at 6 and 24 h.

PMID- 22644640
TI  - Velogenic newcastle disease virus as an oncolytic virotherapeutics: in vitro
      characterization.
AB  - Cancer is one of the killer diseases in humans and needs alternate curative
      measures despite recent improvement in modern treatment modalities. Oncolytic
      virotherapy seems to be a promising nonconventional way to treat cancers.
      Newcastle disease virus (NDV), a poultry virus, is nonpathogenic to human and
      domestic animals and has a long history of being used in oncotherapy research in
      several preclinical studies. The ability of NDV to successfully infect and
      destroy cancer cells is dependent on the strain and the pathotype of the virus.
      Adaptation of viruses to heterologous hosts without losing its replicative and
      oncolytic potential is prerequisite for use as cancer virotherapeutics. In the
      present study, velogenic NDV was adapted for replication in HeLa cells, and its
      cytotoxic potential was evaluated by observing morphological, biochemical, and
      nuclear landmarks of apoptosis. Our results indicated that the NDV-induced
      apoptosis in HeLa cells was dependent on upregulation of TNF-related apoptosis
      inducing ligand (TRAIL) and caspases activation. Different determinants of
      apoptosis evaluated in the present study indicated that this strain could be a
      promising candidate for cancer therapy in future.

PMID- 22644641
TI  - Amperometric vitamin C biosensor based on the immobilization of ascorbate oxidase
      into the biocompatible sandwich-type composite film.
AB  - Ascorbate oxidase (AO), a biologically active macromolecule, was successfully
      immobilized into a biocompatible sandwich-type composite film for developing the
      vitamin C (VC) biosensor, and the content of VC in commercial juices was
      amperometrically determined. The biocompatible and conducting poly(3,4
      ethylenedioxythiophene) composite film and highly stable and selective
      multiwalled carbon nanotubes -Nafion composite film were prepared as inner and
      outer films of biosensor. AO molecules were immobilized between these two
      composite films. The as-fabricated biosensor displayed an excellent
      bioelectrocatalytic performance towards the oxidation of VC, a fast current
      response, a low working potential, a high sensitivity, a wide linear range, and a
      low detection limit. Moreover, the working mechanism of the biosensor was
      proposed, and its kinetics was also discussed. In addition, the specificity,
      reproducibility, and feasibility of the as-fabricated biosensor were also
      evaluated. Good results of the VC determination in commercial juices indicated
      that the as-fabricated biosensor was a potential candidate for the
      electrochemical determination of VC in agricultural crops. Inner and outer films
      provided a promising platform for the immobilization of biologically active
      species.

PMID- 22644643
TI  - Optimization of a natural medium for cellulase by a marine Aspergillus niger
      using response surface methodology.
AB  - The components of a natural medium were optimized to produce cellulase from a
      marine Aspergillus niger under solid state fermentation conditions by response
      surface methodology. Eichhornia crassipes and natural seawater were used as a
      major substrate and a source of mineral salts, respectively. Mineral salts of
      natural seawater could increase cellulase production. Raw corn cob and raw rice
      straw showed a significant positive effect on cellulase production. The optimum
      natural medium consisted of 76.9 % E. crassipes (w/w), 8.9 % raw corn cob (w/w),
      3.5 % raw rice straw (w/w), 10.7 % raw wheat bran (w/w), and natural seawater
      (2.33 times the weight of the dry substrates). Incubation for 96 h in the natural
      medium increased the biomass to the maximum. The cellulase production was 17.80
      U/g the dry weight of substrates after incubation for 144 h. The natural medium
      avoided supplying chemicals and pretreating substrates. It is promising for
      future practical fermentation of environment-friendly producing cellulase.

PMID- 22644642
TI  - Chemical composition, antioxidant and anticancer effects of the seeds and leaves
      of indigo (Polygonum tinctorium Ait.) plant.
AB  - Seeds and leaves of indigo (Polygonum tinctorium Ait.) plant were investigated
      and compared with another medicinal plant named prolipid for their properties
      such as chemical composition, antioxidant, and anticancer effects by Fourier
      transform infrared, three-dimensional fluorescence spectroscopy, and electrospray
      ionization-MS in negative mode. It was found that polyphenols, flavonoids, and
      flavanols were significantly higher in prolipid (P<0.05), following by indigo
      mature leaves, immature leaves, and seeds. Methanol extract of mature indigo
      leaves in comparison with the ethyl acetate extract showed higher inhibition of
      proliferation. The interaction between polyphenol extracts of indigo mature
      leaves and BSA showed that indigo has a strong ability, as other widely used
      medicinal plants, to quench the intrinsic fluorescence of BSA by forming
      complexes. In conclusion, indigo mature leaves were compared with prolipid. High
      content of bioactive compounds, antioxidant, fluorescence, and antiproliferative
      properties of indigo justifies the use of this plant as a medicinal plant and a
      new source of antioxidants.

PMID- 22644644
TI  - Gamma-cyclodextrin production using cyclodextrin glycosyltransferase from
      Bacillus clarkii 7364.
AB  - The production of cyclodextrins (CDs) by cyclodextrin glycosyltransferase
      (CGTase) from Bacillus clarkii 7364 was studied. Forty-seven percent (w/w)
      conversion rate to gamma-CD was obtained in the process performed by reacting 5 U
      per gram of starch CGTase with 15 % (w/v) soluble starch in 0.025 M sodium
      phosphate-NaOH buffer (pH 12) at 55  degrees C in the presence of 2 % (w/v)
      glycyrrhizic acid. Meanwhile, the ratio of gamma:beta-CD was 89:11, with
      negligible formation of alpha-CD. Under these conditions, there is a significant
      increase in overall production of CDs and a marked change in product selectivity
      for gamma-CD. The possible mechanisms were discussed upon different product
      profiles with respect to the size and amount of CDs synthesized at different
      reaction conditions. The approach described here can be easily applied to an
      enzymatic process for the production of gamma-CD on an industrial scale, and such
      high selectivity, at high conversions, is especially attractive from a commercial
      perspective.

PMID- 22644645
TI  - Ag(I) ion mediated formation of a C-A mispair by DNA polymerases.
AB  - Silver turns up the A-C: In the presence of Ag(I) ions, a DNA polymerase
      incorporated deoxyadenosine (from dATP) at the site opposite cytosine in the
      template strand to afford the full-length product (see scheme), meaning that DNA
      polymerases prefer a C-Ag(I)-A base pair to the more thermodynamically stable C
      Ag(I)-C base pair.

PMID- 22644646
TI  - Internet-based self-management compared with usual care in adolescents with
      asthma: a randomized controlled trial.
AB  - INTRODUCTION: Asthma control often is poor in adolescents and this causes
      considerable morbidity. Internet-based self-management (IBSM) improves asthma
      related quality of life in adults. We hypothesized that IBSM improves asthma
      related quality of life in adolescents. METHODS: Adolescents (12-18 years) with
      persistent and not well-controlled asthma participated in a randomized controlled
      trial with 1 year follow-up and were allocated to IBSM (n = 46) or usual care
      (UC, n = 44). IBSM consisted of weekly asthma control monitoring with treatment
      advice by a web-based algorithm. Outcomes included asthma-related quality of life
      (Pediatric Asthma Quality of Life Questionnaire, PAQLQ) and asthma control
      (Asthma Control Questionnaire, ACQ) and were analyzed by a linear mixed-effects
      model. RESULTS: At 3 months, PAQLQ improved with 0.40 points (95% CI: 0.17-0.62,
      P < 0.01), by IBSM compared to 0.0 points for UC (P = 0.02 for the difference).
      At 12 months the between-group difference was -0.05 (95% CI: -0.50 to 0.41, P =
      0.85). At 3 months ACQ improved more in IBSM than in UC (difference: -0.32
      points; 95% CI: -0.56 to -0.079, P < 0.01). At 12 months the difference was -0.05
      (95% CI: -0.35 to 0.25, P = 0.75). CONCLUSION: IBSM improved asthma-related
      quality of life and asthma control in adolescents with not well-controlled asthma
      after 3 months, but not after 12 months.

PMID- 22644647
TI  - The mechanism of BH4 -responsive hyperphenylalaninemia--as it occurs in the
      ENU1/2 genetic mouse model.
AB  - The Pah(enu1/enu2) (ENU1/2) mouse is a heteroallelic orthologous model displaying
      blood phenylalanine (Phe) concentrations characteristic of mild
      hyperphenylalaninemia. ENU1/2 mice also have reduced liver phenylalanine
      hydroxylase (PAH) protein content (~20% normal) and activity (~2.5% normal). The
      mutant PAH protein is highly ubiquitinated, which is likely associated with its
      increased misfolding and instability. The administration of a single subcutaneous
      injection of l-Phe (1.1 mg l-Phe/g body weight) leads to an approximately twofold
      to threefold increase of blood Phe and phenylalanine/tyrosine (Phe/Tyr) ratio,
      and a 1.6-fold increase of both nonubiquitinated PAH protein content and PAH
      activity. It also results in elevated concentrations of liver 6R-l-erythro
      5,6,7,8-tetrahydrobiopterin (BH(4)), potentially through the influence of Phe on
      GTP cyclohydrolase I and its feedback regulatory protein. The increased BH(4)
      content seems to stabilize PAH. Supplementing ENU1/2 mice with BH(4) (50
      mg/kg/day for 10 days) reduces the blood Phe/Tyr ratio within the mild
      hyperphenylalaninemic range; however, PAH content and activity were not elevated.
      It therefore appears that BH(4) supplementation of ENU1/2 mice increases Phe
      hydroxylation levels through a kinetic rather than a chaperone stabilizing
      effect. By boosting blood Phe concentrations, and by BH(4) supplementation, we
      have revealed novel insights into the processing and regulation of the ENU1/2
      mutant PAH.

PMID- 22644648
TI  - The 2012 core content of medical toxicology.

PMID- 22644657
TI  - Bidirectional photocontrol of peptide conformation with a bridged azobenzene
      derivative.
AB  - It goes both ways: A thiol-reactive cross-linker based on a bridged azobenzene
      derivative permits photoreversible control of peptide conformation on irradiation
      with violet (407 nm) and green (500-550 nm) light (see picture) through
      isomerization of the cross-linker. The large separation of the absorbance bands
      of the cis (yellow) and trans (red) isomers enables complete bidirectional
      photoswitching.

PMID- 22644656
TI  - Upregulation of mucin4 in ER-positive/HER2-overexpressing breast cancer
      xenografts with acquired resistance to endocrine and HER2-targeted therapies.
AB  - We studied resistance to endocrine and HER2-targeted therapies using a xenograft
      model of estrogen receptor positive (ER)/HER2-overexpressing breast cancer. Here,
      we report a novel phenotype of drug resistance in this model. MCF7/HER2-18
      xenografts were treated with endocrine therapy alone or in combination with
      lapatinib and trastuzumab (LT) to inhibit HER2. Archival tumor tissues were
      stained with hematoxylin and eosin and with mucicarmine. RNA extracted from
      tumors at early time points and late after acquired resistance were analyzed for
      mucin4 (MUC4) expression by microarray and quantitative reverse transcriptase
      PCR. Protein expression of the MUC4, ER, and HER2 signaling pathways was measured
      by immunohistochemistry and western blotting. The combination of the potent anti
      HER2 regimen LT with either tamoxifen (Tam + LT) or estrogen deprivation (ED +
      LT) can cause complete eradication of ER-positive/HER2-overexpressing tumors in
      mice. Tumors developing resistance to this combination, as well as those
      acquiring resistance to endocrine therapy alone, exhibited a distinct
      histological and molecular phenotype-a striking increase in mucin-filled vacuoles
      and upregulation of several mucins including MUC4. At the onset of resistance,
      MUC4 mRNA and protein were increased. These tumors also showed upregulation and
      reactivation of HER2 signaling, while losing ER protein and the estrogen
      regulated gene progesterone receptor. Mucins are upregulated in a preclinical
      model of ER-positive/HER2-overexpressing breast cancer as resistance develops to
      the combination of endocrine and anti-HER2 therapy. These mucin-rich tumors
      reactivate the HER2 pathway and shift their molecular phenotype to become more ER
      negative/HER2-positive.

PMID- 22644658
TI  - Recent advances in azaborine chemistry.
AB  - The chemistry of organoboron compounds has been primarily dominated by their use
      as powerful reagents in synthetic organic chemistry. Recently, the incorporation
      of boron as part of a functional target structure has emerged as a useful way to
      generate diversity in organic compounds. A commonly applied strategy is the
      replacement of a CC unit with its isoelectronic BN unit. In particular, the BN/CC
      isosterism of the ubiquitous arene motif has undergone a renaissance in the past
      decade. The parent molecule of the 1,2-dihydro-1,2-azaborine family has now been
      isolated. New mono- and polycyclic B,N heterocycles have been synthesized for
      potential use in biomedical and materials science applications. This review is a
      tribute to Dewar's first synthesis of a monocyclic 1,2-dihydro-1,2-azaborine 50
      years ago and discusses recent advances in the synthesis and characterization of
      heterocycles that contain carbon, boron, and nitrogen.

PMID- 22644659
TI  - Folate-deficiency induced cell-specific changes in the distribution of
      lymphocytes and granulocytes in rats.
AB  - OBJECTIVE: Folate (vitamin B(9)) plays key roles in cell growth and proliferation
      through regulating the synthesis and stabilization of DNA and RNA, and its
      deficiency leads to lymphocytopenia and granulocytopenia. However, precisely how
      folate deficiency affects the distribution of a variety of white blood cell
      subsets, including the minor population of basophils, and the cell specificity of
      the effects remain unclear. Therefore, we examined the effects of a folate
      deficient diet on the circulating number of lymphocyte subsets [T-lymphocytes, B
      lymphocytes, and natural killer (NK) cells] and granulocyte subsets (neutrophils,
      eosinophils, and basophils) in rats. METHODS: Rats were divided into two groups,
      with one receiving the folate-deficient diet (FAD group) and the other a control
      diet (CON group). All rats were pair-fed for 8 weeks. RESULTS: Plasma folate
      level was dramatically lower in the FAD group than in the CON group, and the
      level of homocysteine in the plasma, a predictor of folate deficiency was
      significantly higher in the FAD group than in the CON group. The number of T
      lymphocytes, B-lymphocytes, and NK cells was significantly lower in the FAD group
      than in the CON group by 0.73-, 0.49-, and 0.70-fold, respectively, indicating
      that B-lymphocytes are more sensitive to folate deficiency than the other
      lymphocyte subsets. As expected, the number of neutrophils and eosinophils was
      significantly lower in the FAD group than in the CON group. However, the number
      of basophils, the least common type of granulocyte, showed transiently an
      increasing tendency in the FAD group as compared with the CON group. CONCLUSION:
      These results suggest that folate deficiency induces lymphocytopenia and
      granulocytopenia in a cell-specific manner.

PMID- 22644660
TI  - The antidiabetic effect of mesenchymal stem cells is unrelated to their
      transdifferentiation potential but to their capability to restore Th1/Th2 balance
      and to modify the pancreatic microenvironment.
AB  - Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that results from
      cell-mediated autoimmune destruction of insulin-producing cells. In T1DM animal
      models, it has been shown that the systemic administration of multipotent
      mesenchymal stromal cells, also referred as to mesenchymal stem cells (MSCs),
      results in the regeneration of pancreatic islets. Mechanisms underlying this
      effect are still poorly understood. Our aims were to assess whether donor MSCs
      (a) differentiate into pancreatic beta-cells and (b) modify systemic and
      pancreatic pathophysiologic markers of T1DM. After the intravenous administration
      of 5 * 10(5) syngeneic MSCs, we observed that mice with T1DM reverted their
      hyperglycemia and presented no donor-derived insulin-producing cells. In
      contrast, 7 and 65 days post-transplantation, MSCs were engrafted into secondary
      lymphoid organs. This correlated with a systemic and local reduction in the
      abundance of autoaggressive T cells together with an increase in regulatory T
      cells. Additionally, in the pancreas of mice with T1DM treated with MSCs, we
      observed a cytokine profile shift from proinflammatory to antinflammatory. MSC
      transplantation did not reduce pancreatic cell apoptosis but recovered local
      expression and increased the circulating levels of epidermal growth factor, a
      pancreatic trophic factor. Therefore, the antidiabetic effect of MSCs
      intravenously administered is unrelated to their transdifferentiation potential
      but to their capability to restore the balance between Th1 and Th2 immunological
      responses along with the modification of the pancreatic microenvironment. Our
      data should be taken into account when designing clinical trials aimed to
      evaluate MSC transplantation in patients with T1DM since the presence of
      endogenous precursors seems to be critical in order to restore glycemic control.

PMID- 22644661
TI  - Scientific workflow systems: Pipeline Pilot and KNIME.

PMID- 22644662
TI  - Leukocytes from wheezing infants release lower amounts of IL-12 and IFN-gamma
      compared to non-wheezing infants.
AB  - OBJECTIVE: This study investigated environmental endotoxin exposure during early
      life, sensitization to aeroallergens, the production of cytokines by LPS
      stimulated leukocytes, and the development of a wheezing phenotype in a
      prospective cohort of infants with high risk of developing allergic diseases.
      MATERIALS AND METHODS: Eighty-four infants were followed from birth until 30
      months of age. We assessed endotoxin concentration in house dust of their homes
      during the first 6 months of life. At age 30 months they were clinically
      evaluated to determine the development of wheezing and other clinical events,
      were skin prick tested, and had blood samples collected for the evaluation of
      cytokine release by LPS-stimulated peripheral blood mononuclear cells (PBMC).
      RESULTS: The level of endotoxin exposure during early life was not associated
      with development of a wheezing phenotype. On the other hand a higher incidence of
      respiratory infections occurred among recurrent wheezing (RW) infants. PBMC from
      RW children exposed to higher levels of environmental endotoxin (above 50 EU/mg)
      released less Interleukin (IL)-12p70 and IFN-gamma compared to the non-RW group.
      TNF-alpha, IL-10, IL-4, IL-5, and IL17 production by LPS-stimulated PBMC from RW
      and non-RW children was equivalent in both groups of environmental endotoxin
      exposure. CONCLUSION: In this prospective cohort of infants with high risk of
      developing allergic diseases we observed that RW and non-RW children were exposed
      to similar levels of endotoxin early in life. LPS-stimulated PBMC from RW infants
      exposed to higher levels of endotoxin released significantly less IL-12 and IFN
      gamma compared to non-RW infants.

PMID- 22644663
TI  - Testing inferences in developmental evolution: the forensic evidence principle.
AB  - Developmental evolution (DE) examines the influence of developmental mechanisms
      on biological evolution. Here we consider the question: "what is the evidence
      that allows us to decide whether a certain developmental scenario for an
      evolutionary change is in fact "correct" or at least falsifiable?" We argue that
      the comparative method linked with what we call the "forensic evidence principle"
      (FEP) is sufficient to conduct rigorous tests of DE scenarios. The FEP states
      that different genetically mediated developmental causes of an evolutionary
      transformation will leave different signatures in the development of the derived
      character. Although similar inference rules have been used in practically every
      empirical science, we expand this approach here in two ways: (1) we justify the
      validity of this principle with reference to a well-known result from
      mathematical physics, known as the symmetry principle, and (2) propose a specific
      form of the FEP for DE: given two or more developmental explanations for a
      certain evolutionary event, say an evolutionary novelty, then the evidence
      discriminating between these hypotheses will be found in the most proximal
      internal drivers of the derived character. Hence, a detailed description of the
      ancestral and derived states, and their most proximal developmental drivers are
      necessary to discriminate between various evolutionary developmental hypotheses.
      We discuss how this stepwise order of testing is necessary, establishes a formal
      test, and how skipping this order of examination may violate a more accurate
      examination of DE. We illustrate the approach with an example from avian digit
      evolution.

PMID- 22644664
TI  - Effects of long-term fixed orthodontic treatment on salivary nickel and chromium
      levels: a 1-year prospective cohort study.
AB  - Effect of long-term orthodontic treatment on salivary nickel and chromium has not
      been quite assessed except in few retrospective studies with controversial
      results. The aim of this prospective study was to measure salivary levels of
      these ions during 1 year of orthodontic treatment. Saliva samples were collected
      from 20 orthodontic patients, before treatment (control) and 6 and 12 months
      later. Nickel and chromium concentrations were determined using atomic absorption
      spectrophotometry. Data were analyzed using one- and two-way repeated-measures
      ANOVA, Bonferroni, Friedman (alpha = 0.05), and Wilcoxon signed-ranks tests
      (alpha = 0.016). Average nickel level changed from 9.75 +/- 5.02 to 10.37 +/-
      6.94 and then to 8.32 +/- 4.36 MUg/L in 1 year. Average chromium concentration
      changed from 3.86 +/- 1.34 to 4.6 +/- 6.11 and then to 2.04 +/- 1.66 MUg/L.
      Alterations in nickel values were not statistically significant [P = 0.468
      (ANOVA)], but fluctuations in chromium levels were [P = 0.021 (Friedman)]. The
      decrease in chromium concentration after 12 months was significant compared to
      the control [P = 0.004 (Wilcoxon)]. Although slightly increased after 6 months,
      the concentration of both ions dropped to levels slightly lower than the control
      groups after 12 months.

PMID- 22644665
TI  - Clustering of place of birth for women with breast cancer: differences by tumor
      characteristics.
AB  - PURPOSE: There is increasing evidence that exposures in early life affect breast
      cancer risk, and that breast cancer etiology differs by tumor subtype. If
      environmental exposures in early life contribute to risk, it is expected that
      there would be clustering of women with breast cancer by their place of birth,
      and that clustering might differ by subtype. We examined spatial associations
      between place of birth and breast cancer by subtype, using hormone receptor
      status and molecular profiles of breast tumors. METHODS: Data were drawn from the
      Western New York Exposures and Breast Cancer study, a population-based case
      control study of incident, pathologically confirmed breast cancer (1996-2001) in
      Erie and Niagara Counties. Included were women born in the study area (579 cases
      and 931 controls). Clustering of breast cancer subgroups relative to controls was
      examined by the k-function method in groups stratified by estrogen receptor (ER),
      progesterone receptor (PR), and HER2 status, and by DNA methylation status and
      p53 mutation status, and the k-function difference was used to compare relative
      spatial aggregation and spatial range of the difference between case subgroups
      and controls. RESULTS: We found a tendency to cluster among ER positive, PR
      positive, and HER2 negative cases (i.e., luminal A subtype), especially among
      premenopausal women, but not among the other groups defined by hormonal receptor
      status, or by either methylation or p53 mutation status. CONCLUSIONS: While our
      findings cannot rule out clustering of cases by birth place because of shared
      behaviors related to residence location, they also suggest that early life
      environmental exposures may affect subsequent breast cancer risk, and that
      premenopausal breast tumors of the luminal A subtype may be more affected by
      these early life exposures than other subtypes.

PMID- 22644666
TI  - Deconvoluting interspecies bacterial communication.
AB  - The universal bacterial signal molecule autoinducer-2 (AI-2) is derived from 4,5
      dihydroxy-2,3-pentanedione (DPD). DPD exists in a complex equilibrium between
      multiple forms, and NMR spectroscopy has now been used to establish that the
      extent of the structural diversity displayed by DPD over a broad pH range is even
      greater than previously posited.

PMID- 22644667
TI  - An electron-rich molybdenum-molybdenum quintuple bond spanned by one lithium
      atom.
AB  - Take five: A unique quintuply bonded dimolybdenum complex [Mo(2)(MU-Li){MU-HC(N
      2,6-Et(2)C(6)H(3))(2)}(3)] (see picture) was synthesized and characterized. The
      Mo-Mo interaction includes an unexpected bridging Li(+) ion. Calculations
      indicate the bridging Li(+) ion does not perturb the Mo-Mo bond length (2.0612(4)
      A), but results in a relatively small effective Mo-Mo bond order of 3.67.

PMID- 22644668
TI  - Structural characterization and surface activities of biogenic rhamnolipid
      surfactants from Pseudomonas aeruginosa isolate MN1 and synergistic effects
      against methicillin-resistant Staphylococcus aureus.
AB  - The aim of present work was to study chemical structures and biological
      activities of rhamnolipid biosurfactants produced by Pseudomonas aeruginosa MN1
      isolated from oil-contaminated soil. The results of liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) analysis revealed that total rhamnolipids (RLs)
      contained 16 rhamnolipid homologues. Di-lipid RLs containing C(10)-C(10) moieties
      were by far the most predominant congeners among mono-rhamnose (53.29 %) and di
      rhamnose (23.52 %) homologues. Mono-rhamnolipids form 68.35 % of the total
      congeners in the RLs. Two major fractions were revealed in the thin layer
      chromatogram of produced RLs which were then purified by column chromatography.
      The retardation factors (R (f)) of the two rhamnolipid purple spots were 0.71 for
      RL1 and 0.46 for RL2. LC-MS/MS analysis proved that RL1 was composed of mono-RLs
      and RL2 consisted of di-RLs. RL1 was more surface-active with the critical
      micelle concentration (CMC) value of 15 mg/L and the surface tension of 25 mN/m
      at CMC. The results of biological assay showed that RL1 is a more potent
      antibacterial agent than RL2. All methicillin-resistant Staphylococcus aureus
      (MRSA) strains were inhibited by RLs that were independent of their antibiotic
      susceptibility patterns. RLs remarkably enhanced the activity of oxacillin
      against MRSA strains and lowered the minimum inhibitory concentrations of
      oxacillin to the range of 3.12-6.25 MUg/mL.

PMID- 22644669
TI  - Amniotic fluid stem cells restore the muscle cell niche in a HSA-Cre, Smn(F7/F7)
      mouse model.
AB  - Mutations in the survival of motor neuron gene (SMN1) are responsible for spinal
      muscular atrophy, a fatal neuromuscular disorder. Mice carrying a homozygous
      deletion of Smn exon 7 directed to skeletal muscle (HSA-Cre, Smn(F7/F7) mice)
      present clinical features of human muscular dystrophies for which new therapeutic
      approaches are highly warranted. Herein we demonstrate that tail vein
      transplantation of mouse amniotic fluid stem (AFS) cells enhances the muscle
      strength and improves the survival rate of the affected animals. Second, after
      cardiotoxin injury of the Tibialis Anterior, only AFS-transplanted mice
      efficiently regenerate. Most importantly, secondary transplants of satellite
      cells (SCs) derived from treated mice show that AFS cells integrate into the
      muscle stem cell compartment and have long-term muscle regeneration capacity
      indistinguishable from that of wild-type-derived SC. This is the first study
      demonstrating the functional and stable integration of AFS cells into the
      skeletal muscle, highlighting their value as cell source for the treatment of
      muscular dystrophies.

PMID- 22644672
TI  - A tunable ratiometric pH sensor based on carbon nanodots for the quantitative
      measurement of the intracellular pH of whole cells.
AB  - The whole picture: Carbon nanodots labeled with two fluorescent dyes have been
      developed as a tunable ratiometric pH sensor to measure intracellular pH. The
      nanosensor shows good biocompatibility and cellular dispersibility. Quantitative
      determinations on intact HeLa cells and pH fluctuations associated with oxidative
      stress were performed.

PMID- 22644671
TI  - ACR Appropriateness Criteria(r) pulsatile abdominal mass, suspected abdominal
      aortic aneurysm.
AB  - Clinical palpation of a pulsating abdominal mass alerts the clinician to the
      presence of a possible abdominal aortic aneurysm (AAA). Generally an arterial
      aneurysm is defined as a localized arterial dilatation >=50% greater than the
      normal diameter. Imaging studies are important in diagnosing the cause of a
      pulsatile abdominal mass and, if an AAA is found, in determining its size and
      involvement of abdominal branches. Ultrasound (US) is the initial imaging
      modality of choice when a pulsatile abdominal mass is present. Noncontrast
      computed tomography (CT) may be substituted in patients for whom US is not
      suitable. When aneurysms have reached the size threshold for intervention or are
      clinically symptomatic, contrast-enhanced multidetector CT angiography (CTA) is
      the best diagnostic and preintervention planning study, accurately delineating
      the location, size, and extent of aneurysm and the involvement of branch vessels.
      Magnetic resonance angiography (MRA) may be substituted if CT cannot be
      performed. Catheter arteriography has some utility in patients with significant
      contraindications to both CTA and MRA. The American College of Radiology
      Appropriateness Criteria((r)) 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- 22644673
TI  - The significance of ionic bonding in sulfur dioxide: bond orders from X-ray
      diffraction data.

PMID- 22644674
TI  - Concise review: stem cell-derived erythrocytes as upcoming players in blood
      transfusion.
AB  - Blood transfusions have become indispensable to treat the anemia associated with
      a variety of medical conditions ranging from genetic disorders and cancer to
      extensive surgical procedures. In developed countries, the blood supply is
      generally adequate. However, the projected decline in blood donor availability
      due to population ageing and the difficulty in finding rare blood types for
      alloimmunized patients indicate a need for alternative red blood cell (RBC)
      transfusion products. Increasing knowledge of processes that govern
      erythropoiesis has been translated into efficient procedures to produce RBC ex
      vivo using primary hematopoietic stem cells, embryonic stem cells, or induced
      pluripotent stem cells. Although in vitro-generated RBCs have recently entered
      clinical evaluation, several issues related to ex vivo RBC production are still
      under intense scrutiny: among those are the identification of stem cell sources
      more suitable for ex vivo RBC generation, the translation of RBC culture methods
      into clinical grade production processes, and the development of protocols to
      achieve maximal RBC quality, quantity, and maturation. Data on size, hemoglobin,
      and blood group antigen expression and phosphoproteomic profiling obtained on
      erythroid cells expanded ex vivo from a limited number of donors are presented as
      examples of the type of measurements that should be performed as part of the
      quality control to assess the suitability of these cells for transfusion. New
      technologies for ex vivo erythroid cell generation will hopefully provide
      alternative transfusion products to meet present and future clinical
      requirements.

PMID- 22644677
TI  - Lung ultrasound in evaluation of pneumonia.

PMID- 22644676
TI  - Increased expression of Rab25 in breast cancer correlates with lymphatic
      metastasis.
AB  - Breast cancer is the most common cancer in women worldwide. Studies have
      suggested that Ras-related protein 25 (Rab25), a member of Rab small GTPase
      family, is involved in the pathogenesis of breast cancer. In this study, we
      investigated whether the expression of Rab25 correlated with lymphatic metastasis
      in breast cancer and whether the expression of Rab25 was positively correlated
      with oestrogen receptor (ER) and progesterone receptor (PR) expression in breast
      cancer. Breast cancer tissues from 42 invasive ductal breast cancer patients with
      or without lymphatic metastasis were collected and the levels of Rab25 mRNA and
      protein measured by quantitative real-time PCR and immunohistochemistry,
      respectively. The mRNA level of Rab25 was significantly increased in invasive
      ductal breast cancer with lymphatic metastasis compared to that in invasive
      ductal breast cancer without lymphatic metastasis. Immunohistochemical analysis
      demonstrated that Rab25 and vascular endothelial growth factor (VEGF) were highly
      expressed in invasive ductal breast cancer with lymphatic metastasis regardless
      of whether the cancer is ER and PR positive or negative. Higher expression of
      Rab25 positively correlated with VEGF expression. However, the expressions of
      Rab25 in ER and PR-positive cancers were much higher than ER and PR-negative
      cancers regardless of whether lymphatic metastasis occurred. These data suggest
      that higher level of Rab25 was associated with lymphatic metastasis, specifically
      in ER and PR-positive breast cancer. The better understanding of the mechanism of
      Rab25 may provide a basis for the development of a novel therapeutic target in
      breast cancer.

PMID- 22644675
TI  - MTA1 expression correlates significantly with ER-alpha methylation in breast
      cancer.
AB  - Metastasis tumor antigen 1 (MTA1), a novel candidate metastasis-associated gene,
      is known to increase the migration and invasion of various tumor cells in vitro.
      It also plays an important role in tumorigenesis and tumor aggressiveness of
      breast cancer. Estrogen receptor alpha (ERalpha) plays an important role in the
      etiology of breast cancer and has been widely accepted as a prognostic marker for
      breast cancer and a response predictor for endocrine therapy. The ERalpha gene
      methylation has been linked to the lack of ERalpha expression in breast cancer.
      The aim of the study is to assess the correlation between the ERalpha methylation
      and MTA1 expression in breast cancer and further to investigate whether the
      repressed ERalpha methylation can downregulate the expression of MTA1 in vitro.
      In general, we found ERalpha methylation had significant correlation with the
      MTA1 expression (p < 0.05) in female patients of breast cancer (n = 102) by
      methylation-specific polymerase chain reaction and immunohistochemistry. To gain
      a deeper insight into the molecular mechanism underlying the relation between
      MTA1 and ERalpha methylation, we treated the invasive breast cancer cell lines
      with the demethylating agent, found the downregulation of MTA1 protein
      expression, and mRNA with the unmethylation of ERalpha (p < 0.05). And the
      invasive ability of breast cancer cells was significantly positively associated
      with MTA1 expression. These unique findings have greatly extended our current
      knowledge about the relation between ERalpha methylation and MTA1 expression.
      These data strongly support the hypothesis that methylation is involved in the
      relation between MTA1 and ERalpha in breast cancer.

PMID- 22644678
TI  - Sonographic detection of unilateral hip dislocation in a spica cast after closed
      reduction for developmental dysplasia of the hip.
AB  - OBJECTIVES: To determine the value of sonography for evaluating unilateral hip
      dislocation in a spica cast after closed reduction for developmental dysplasia of
      the hip. METHODS: Seventy-three cases of unilateral hip dislocation were detected
      by sonography after closed reduction and monitored through the perineal opening
      of the cast during follow-up. The transinguinal approach was used first to
      determine the position of the femoral head. Then a sonogram of the bilateral hips
      was obtained by transverse scanning on the lower margin of the pubic symphysis.
      To determine the status of the affected femoral head, a bilateral comparison of
      the femoral head positions was made by measuring the horizontal distance from the
      medial rim of each femoral head to a center line through the pubic symphysis.
      RESULTS: In all 73 cases, the femoral head position after reduction could be
      identified by sonography. With the transinguinal approach, the reduction was
      successful in 69 cases and unsuccessful in 4. On the sonograms of the bilateral
      hips, the dislocated femoral heads were repositioned in the acetabular fossa in
      the successful cases and redislocated posterolaterally in the unsuccessful cases.
      Among the successful cases, the position differences were less than 2 mm in 61, 3
      to 4 mm in 7, and 5 mm in 1. In the unsuccessful cases, the positions of the
      bilateral hips were asymmetric; the differences were indecipherable after an
      unsuccessful first reduction but were 3 to 5 mm after a successful second
      reduction. During follow-up, the differences were never greater than 2 mm in the
      cases with initial differences of less than 2 mm and gradually decreased to less
      than 2 mm in those with initial differences of greater than 2 mm. CONCLUSIONS:
      Sonography can be considered as the first imaging tool for evaluating the effect
      of closed reduction for developmental dysplasia of the hip.

PMID- 22644679
TI  - Objective differential characteristics of cystic biliary atresia and choledochal
      cysts in neonates and young infants: sonographic findings.
AB  - OBJECTIVES: To prospectively evaluate the objective differential characteristics
      between cystic biliary atresia and choledochal cysts on sonography among neonates
      and young infants. METHODS: Twenty-three patients who had sonographic findings of
      a portal cyst and a final diagnosis were included. Their final diagnoses were
      cystic biliary atresia in 12 patients and choledochal cysts in 11. All of them
      underwent detailed sonographic scanning. Data for cystic biliary atresia and
      choledochal cyst groups were compared by the chi(2) test for categorical
      variables and an unpaired t test for continuous variables. RESULTS: The
      triangular cord sign was detected in 11 patients in the atresia group but in none
      in the cyst group (P < .001). Nine of 11 patients in the cyst group had
      dilatation of intrahepatic bile ducts, whereas none in the atresia group had that
      feature (P < .001). Sonography also showed sludge deposits in the cysts in 6 of
      11 patients in the cyst group, whereas none in the atresia group had sludge
      deposits (P = .005). The mean width and length of the cysts in the cyst group
      were significantly larger than those in the atresia group (P< .05 for both). The
      mean hepatic artery diameter was significantly larger in the atresia group than
      in the cyst group (P < .001). The difference in gallbladder abnormalities between
      the atresia (n = 11) and cyst (n = 0) groups was also significant (P < .001).
      When all specific sonographic features were used, all patients were correctly
      classified into the atresia and cyst groups. CONCLUSIONS: The triangular cord
      sign, intrahepatic bile duct dilatation, and echoic cysts might be regarded as
      objective sonographic features for differentiating cystic biliary atresia and
      choledochal cysts. Other sonographic features might be very supportive.

PMID- 22644680
TI  - Doppler sonography of patients with and without acute cellular rejection after
      right-lobe living donor liver transplantation.
AB  - OBJECTIVES: To compare percent interval changes in the portal blood flow velocity
      (%PBV) and venous pulsatility index (%VPI), as determined by Doppler sonography,
      in patients with and without acute cellular rejection after right-lobe living
      donor liver transplantation. METHODS: Forty-seven patients with biopsy-proven
      acute cellular rejection underwent Doppler sonography. The control group
      consisted of 47 age- and sex-matched patients without acute cellular rejection.
      Doppler spectrograms of the portal vein and right hepatic vein were used to
      calculate mean peak PBVs and VPIs for the first 3 days after right-lobe living
      donor liver transplantation, defined as PBV(Baseline) and VPI(Baseline). The PBV
      and VPI closest in time to biopsy in the patient group or at a matched time in
      the control group were determined as PBV(Event) and VPI(Event), and %PBV and %VPI
      values were calculated. RESULTS: The mean PBV(Baseline) values +/- SD in the
      rejection and control groups were 46.0 +/- 21.8 and 44.4 +/- 20.5 cm/s,
      respectively; the PBV(Event) values were 32.2 +/- 14.5 and 34.4 +/- 17.1 cm/s;
      and the %PBV values were 19.4% +/- 39.9% and 2.2% +/- 75.4% (P = .73; P = .38; P
      = .17, respectively). The VPI(Baseline) values were 0.92 +/- 0.34 and 0.93 P =
      .94; P < .001); and the +/- 0.38; the VPI(Event) values were 0.46 +/- 0.33 and
      0.84 +/- 0.44 (%VPI values were 45.5% +/- 40.1% and 5.6% +/- 47.3%, with a
      greater than 50% VPI observed more frequently in the rejection than in the
      control group (61.7% versus 12.8%; P < .001). CONCLUSIONS: The VPI(Event) was
      significantly lower and a greater than 50% VPI was significantly more frequent in
      patients with than without acute cellular rejection after right-lobe living donor
      liver transplantation.

PMID- 22644681
TI  - Neuroepithelial transforming protein 1 short interfering RNA-mediated gene
      silencing with microbubble and ultrasound exposure inhibits the proliferation of
      hepatic carcinoma cells in vitro.
AB  - OBJECTIVES: Short interfering RNA (siRNA) has been used to knock down the
      expression of targeted genes in a process known as RNA interference. However, the
      key to RNA interference is the efficient intracellular delivery of the siRNA. In
      this study, we sought to enhance the efficiency of transduction and find a novel
      therapy for hepatic carcinoma. METHODS: Three types of neuroepithelial
      transforming protein 1 (NET-1) siRNAs (labeled fluorescent) were designed and
      transduced into HepG2 cells. Then the most effective one in silencing NET-1 was
      determined. The HepG2 cells were divided into 5 groups: untreated control;
      delivery of siRNA; delivery of siRNA using Lipofectamine 2000 (Invitrogen,
      Carlsbad, CA; group L); delivery of siRNA using ultrasound exposure and
      microbubbles (group US); and delivery of siRNA using Lipofectamine, ultrasound
      exposure, and microbubbles (group LUS). The efficiency of siRNA transfer was
      determined by detection of luciferase activity on microscopy; NET-1 expression
      was assayed by reverse transcription-polymerase chain reaction and western
      blotting; and proliferation investigations of the HepG2 cells were performed.
      RESULTS- The transfection efficiency of microbubbles combined with ultrasound
      exposure was nearly equal to Lipofectamine-mediated transfection (P = .609). More
      importantly, the combination of Lipofectamine, microbubbles, and ultrasound
      exposure effectively reduced NET-1 expression compared with the other groups (P <
      .01). Furthermore, the proliferation of cells in groups L, US, and LUS was
      visibly inhibited between 24 and 72 hours. CONCLUSIONS: The use of a microbubble
      contrast agent combined with ultrasound exposure could be a potent physical
      method for increasing gene delivery efficiency. This technique is a promising
      nonviral approach that can be used in liver cancer.

PMID- 22644682
TI  - Effect of healthy tissue ablation surrounding VX2 rabbit liver tumors by high
      intensity focused ultrasound combined with an ultrasound contrast agent.
AB  - OBJECTIVES: The purpose of this study was to determine the minimum amount of
      healthy peripheral tissue that should be ablated when treating VX2 liver tumors
      with high-intensity focused ultrasound combined with an ultrasound contrast
      agent. METHODS: Fifty-one rabbits with hepatic tumors were established and
      randomly divided into the following groups: group A, which only had their tumors
      ablated; group B, which had their tumors and 2 mm of healthy adjacent tissue
      ablated; and group C, which had their tumors and 4 mm of healthy adjacent tissue
      ablated. The pathologic characteristics of the target tissue, serum alanine
      aminotransferase (ALT) level, presence of intrahepatic and distant metastases,
      and survival time between different groups were compared after high-intensity
      focused ultrasound treatment. RESULTS: After ablation, coagulative necrosis was
      observed in all targeted tissue. The serum ALT level in group C was the highest
      and the level in group A was the lowest on the third and fifth days after
      ablation (P < .05), respectively. Fourteen days later, the serum ALT level in
      groups B and C decreased to normal, whereas the level in group A was abnormal and
      significantly higher (P < .05). Compared with group A, the prevalence of
      metastases in groups B and C was significantly lower (P < .05), and the survival
      time was significantly longer (P < .05); there appeared to be no statistically
      significant difference between groups B and C (P > .05). CONCLUSIONS: Ablation of
      a tumor along with 2 mm of healthy surrounding tissue is a more effective
      strategy for treating hepatic cancer with high-intensity focused ultrasound
      coupled with an ultrasound contrast agent.

PMID- 22644684
TI  - Doppler velocimetry of the ophthalmic artery: reproducibility of blood flow
      velocity measurements.
AB  - OBJECTIVES: The aim of this study was to investigate the interobserver
      reliability for measuring ophthalmic artery Doppler indices. METHODS: Healthy
      women (n = 30) were evaluated. The resistive index, pulsatility index, and peak
      ratio were determined by two independent observers who were blind to each other.
      A paired t test was used for the comparison of paired samples in the cases of
      replication between observers. Pearson product-moment correlation was used to
      study the relationship between the samples. The Bland-Altman graphic approach was
      used to investigate the agreement between observers. RESULTS: No significant
      differences were found between the values obtained by the two independent
      observers for the resistive index and pulsatility index. The difference observed
      between the values obtained by the observers for the peak ratio was 0.02.
      CONCLUSIONS: Doppler velocimetry is a reproducible technique for evaluation of
      the resistive index and pulsatility index. For analysis of the peak ratio, an
      interval of +/-0.02 should be considered for the measurement.

PMID- 22644683
TI  - Sonographically guided radiofrequency ablation with and without a superficial
      saline injection to prevent skin burns in a rabbit model.
AB  - OBJECTIVES: Our aim was to determine whether sonographically guided
      radiofrequency ablation with superficial saline injection can minimize thermal
      injury of the skin without an influence on therapeutic efficacy. METHODS:
      Institutional Animal Care Committee approval was obtained. Twelve percutaneous
      radiofrequency ablation procedures were performed in the thighs of 6 rabbits
      (control, n = 6, right thigh; experimental, n = 6, left thigh). The ablation with
      local anesthesia was performed in the most superficial area of the thigh muscle.
      In the experimental group, 1 mL of saline was injected before the ablation at the
      tissue layer between the skin and ablated muscle. The duration and energy of the
      ablation were the same in the control and experimental groups. Rabbits were
      compared for their gross skin state and histopathologic findings after the
      ablation. RESULTS: The degree of thermal coagulation of the muscle was similar in
      both groups at pathologic examination. Grossly, skin redness was mild in the
      experimental group but moderate in the control group. Of the 6 rabbits, 5 tended
      to show more frequent histopathologic changes, including an inflammatory
      reaction, interruption of collagen fibers, injury of the skin adnexa, and
      fibrosis, in the control group when compared with the experimental group.
      However, there was no statistically significant difference (all P> .05). One
      rabbit that underwent ablation at higher energy had a partially dissected
      epidermis in the control group only. CONCLUSIONS: Sonographically guided
      radiofrequency ablation with a saline injection superficial to a tumor might
      prevent skin burns and provide equivalent therapeutic efficacy for ablating
      superficial lesions.

PMID- 22644685
TI  - New image processing technique for evaluating breast microcalcifications: a
      comparative study.
AB  - OBJECTIVES: The purpose of this study was to evaluate a new commercial image
      processing technique (MicroPure; Toshiba America Medical Systems, Tustin, CA) for
      identifying breast microcalcifications compared to gray scale ultrasound imaging
      (US) using mammography as the reference standard. METHODS: Twenty women, with
      breast calcifications identified mammographically, underwent gray scale US and
      MicroPure examinations of the breast. Still images and digital clips of the
      target area were acquired using gray scale US and MicroPure (at 3 different
      sensitivity levels: 0, 1, and 2). The images were analyzed by 4 independent and
      blinded readers (2 radiologists and 2 physicists) to determine the number of
      calcifications as well as to score image quality and artifacts. RESULTS: For all
      4 readers, there were significantly more calcifications seen with MicroPure (at
      the 2 highest sensitivity levels) compared to gray scale US (P < .009). Agreement
      between readers consistently increased from gray scale US to MicroPure imaging
      (gray scale intraclass correlation coefficient, 0.02-0.44; versus MicroPure
      intraclass correlation coefficient, 0.34-0.71). The agreement improved between
      mammography and MicroPure (13.2%-28.3%) when compared with mammography and gray
      scale US (1.7%-5.2%); the 2 radiologists saw a bigger improvement. Two readers
      preferred the MicroPure image quality over gray scale US (P < .001) and vice
      versa for the other 2 readers(P < .001). All 4 readers saw fewer artifacts with
      MicroPure (at level 2) than with gray scale US (P < .02). CONCLUSIONS: MicroPure
      imaging identified significantly more breast microcalcifications than gray scale
      US.

PMID- 22644686
TI  - Effects of precompression on elasticity imaging of the breast: development of a
      clinically useful semiquantitative method of precompression assessment.
AB  - OBJECTIVES: Elastography of the breast is a new technique for characterization of
      breast lesions. The reproducibility of elastographic techniques has been
      questioned. Precompression is known to effect elastographic results. This study
      determined the effect of precompression on clinical images and proposes a method
      to semiquantify the amount of precompression applied. METHODS: Ten patients with
      different breast tissue types were evaluated with shear wave and strain
      elastography with varying amounts of precompression. The changes in the shear
      wave speed and images were documented. A semiquantitative method for determining
      the amount of precompression applied is presented. The reproducibility of the
      technique was determine by repeated measurements by 3 sonographers. RESULTS:
      Precompression substantially changes the elastographic results of patient images
      on both strain and shear wave elastography. Fat can have the same elasticity as
      cancer with clinically possible amounts of precompression. The proposed method
      for determining the amount of precompression applied has variability of less than
      10%, which is within the error of the technique and would not affect clinical
      results. Four zones of precompression are identified, which are useful for
      explaining the effects of precompression on both strain and shear wave imaging.
      CONCLUSIONS: Precompression is a substantial factor in obtaining accurate results
      with elastography. A proposed simple, easily applied technique can be used to
      semiquantify the amount of precompression applied. Precompression should be
      minimized in obtaining breast clinical images.

PMID- 22644687
TI  - Contralateral enhancing lesions on magnetic resonance imaging in patients with
      breast cancer: role of second-look sonography and imaging findings of synchronous
      contralateral cancer.
AB  - OBJECTIVES: The purposes of this study were to assess the clinical utility of
      sonography for evaluation of contralateral suspicious lesions detected on
      magnetic resonance imaging (MRI) in patients with breast cancer and to compare
      imaging findings of the index and synchronous contralateral cancers. METHODS: We
      performed breast MRI on 853 consecutive patients with histologically confirmed
      breast cancer between January 2006 and December 2009. All patients underwent
      mammography and whole-breast sonography before MRI. We included 126 contralateral
      enhancing lesions in 98 patients who underwent second-look sonography. Lesions
      with sonographic correlation were biopsied using sonographic guidance, and
      lesions without sonographic correlation were biopsied using computed tomographic
      guidance or followed with imaging modalities. RESULTS: Of 126 suspicious lesions,
      81 (64%) were correlated on sonography, and 45 (36%) were not. Of 81 correlated
      lesions, 16 (20%) were malignant, and 65 (80%) were benign. Of 45 lesions that
      were not correlated on sonography, only 1 (2%) was malignant. Of 17 contralateral
      cancers, 11 were detected on initial sonography and 5 on second-look sonography.
      The index and contralateral cancers showed statistically significant differences
      in the sonographic boundary (P = .003) and posterior echogenicity (P = .013). The
      contralateral cancers detected on initial or second-look sonography showed
      significant differences in the echo pattern (P = .001). CONCLUSIONS: Magnetic
      resonance imaging is a reliable tool for detection of occult contralateral breast
      cancer. With second-look sonography, we can find additional contralateral cancer.
      When enhancing lesions on MRI are not correlated on sonography, MRI- or computed
      tomography-guided biopsy or short-term imaging follow-up should be done.

PMID- 22644688
TI  - Differences in sonographic features of papillary thyroid carcinoma between neck
      lymph node metastatic and nonmetastatic groups.
AB  - OBJECTIVES: The purpose of this study was to assess the differences in
      sonographic features of papillary thyroid carcinoma between neck lymph node
      metastatic and non-metastatic groups. METHODS: A total of 155 patients with 155
      papillary thyroid carcinoma nodules were included and divided into two groups:
      with neck lymph node metastases (52 cases) and without neck lymph node metastases
      (103 cases). The size, shape, border, margin, halo, internal architecture,
      echogenicity, echo homogeneity, calcifications, and contact extent between the
      nodule border and thyroid capsule were evaluated by gray scale sonography, and
      color Doppler sonography was applied to assess the vascularization distribution
      and vascularization degree in the nodules. The peak systolic velocity,
      pulsatility index, resistive index, peak systolic velocity difference,
      pulsatility index difference, and resistive index difference were measured by
      pulsed Doppler sonography in 80 lesions. The differences in the sonographic
      features of papillary thyroid carcinoma between the metastatic and nonmetastatic
      groups were investigated. RESULTS: The differences in the size, percentage of the
      nodule border that contacted the thyroid capsule, calcifications, vascularization
      degree, and resistive index difference of the lesions were statistically
      significant between the metastatic and nonmetastatic groups (P < .05).
      CONCLUSIONS: Our findings suggest that a larger size, a greater contact
      percentage, combined microcalcifications and macrocalcifications, a higher blood
      supply, and a higher resistive index difference were significantly more common in
      the metastatic group compared to the nonmetastatic group.

PMID- 22644689
TI  - Gene expression profiling of rat fetuses exposed to 2-dimensional ultrasound.
AB  - OBJECTIVES: This study evaluated the possible effects of ultrasound (US) on gene
      expression in brain tissue of rat embryos. METHODS: Four groups (n = 5 each) of
      pregnant Wistar Han rats were exposed to US for different durations (55, 100,
      145, and 195 seconds) via a multifrequency transducer in the 2-dimensional
      imaging mode with a pulse duration of 1.29 microseconds, a pulse repetition
      frequency of 1 kHz, and a derated spatial-peak pulse-average intensity of 222.4
      W/cm(2) on day 5, 9, 7, or 13 of gestation. Gene expression profiling was
      performed in fetal brain tissue (n = 5 per group) by quantitative reverse
      transcription-polymerase chain reaction arrays. RESULTS: The results indicated
      substantial alterations in gene expression. The most differentially expressed
      genes were Adamts5, Gadd45a, Npy2r, and Chrna1, which are implicated in important
      developmental signaling pathways. CONCLUSIONS: On the basis of our findings,
      routine short US examinations for monitoring fetal development are not
      contraindicated, but prolonged exposures should be used only when needed to
      obtain important diagnostic information.

PMID- 22644690
TI  - Reliability of 3-dimensional transvaginal sonographic measurement of lower
      uterine segment thickness.
AB  - OBJECTIVES: The purpose of this study was to report the intraobserver and
      interobserver reliability of transvaginal 3-dimensional (3D) sonographic
      measurement of lower uterine segment thickness. METHODS: A prospective study of
      60 pregnant women with previous low transverse cesarean deliveries was performed
      between 35 and 39 weeks' gestation. Two observers, blinded to the clinical data,
      independently measured the full lower uterine segment thickness by 2-dimensional
      (2D) transvaginal sonography. Three-dimensional volume data sets of the lower
      uterine segment were captured and analyzed more than 2 months later by both
      observers independently. Intraobserver, interobserver, and intermethod
      reliability was evaluated by median absolute differences, nonparametric limits of
      agreement, intraclass correlation coefficients (ICCs), and kappa coefficients.
      RESULTS: The median full lower uterine segment thickness was 3.6 mm (range, 0.9
      8.0 mm). Intraobserver reliability (median difference, 0.3 mm [interquartile
      range (IQR), 0.1-0.6 mm]; ICC, 0.88 [95% confidence interval (CI), 0.81-0.93];
      kappa, 0.87 [95% CI, 0.69-1.00]) and interobserver reliability (median
      difference, 0.3 mm [IQR, 0.1-0.5 mm]; ICC, 0.88 [95% CI, 0.81-0.93]; kappa, 0.86
      [95% CI, 0.66-1.00]) were excellent. Reliability between 3D and 2D sonography was
      moderate (median difference, 0.6 mm [IQR, 0.2-0.9 mm]; ICC, 0.78 [95% CI, 0.66
      0.86]; kappa, 0.56 [95% CI, 0.28-0.85]). However, intermethod reproducibility was
      improved when the full lower uterine segment thickness was less than 3.0 mm
      (median difference, 0.4 mm [IQR, 0.2-0.9 mm]). CONCLUSIONS: Full lower uterine
      segment thickness measured with 3D transvaginal sonographic data sets has
      excellent intraobserver and interobserver reliability. It also has good
      reproducibility with 2D sonography when the full lower uterine segment thickness
      is less than 3.0 mm.

PMID- 22644691
TI  - Suspected twin-twin transfusion syndrome: how often is the diagnosis correct and
      referral timely?
AB  - OBJECTIVES: The purpose of this study was to describe a single center's
      experience with referrals suspected to have twin-twin transfusion syndrome.
      METHODS: A retrospective review was performed for patients with suspected twin
      twin transfusion syndrome referred to a fetal treatment center between November
      1, 2006, and June 1, 2010. Data were collected regarding diagnosis, treatment,
      and follow-up. RESULTS: Of the 324 patients referred for twin-twin transfusion
      syndrome, the diagnosis was confirmed in 249 (77%): Quintero stage I in 28 (11%),
      stage II in 50 (20%), stage III in 150 (60%), stage IV in 15 (6%), and stage V in
      6 (2%). Ten patients presented too late for any intervention, including 6 cases
      of stage V disease with either single- or dual-twin death and 4 patients who
      imminently delivered. Of the 249 confirmed cases, 200 (84%) patients elected to
      undergo laser photocoagulation. The average gestational age +/- SD for referral
      evaluation for laser-treated cases was 20.9 +/- 5.7 weeks (median, 20.5 weeks).
      The other 75 patients who were referred for suspected twin-twin transfusion
      syndrome had a diagnosis of either a discordant amniotic fluid volume that did
      not meet the criteria for Quintero stage I twin-twin transfusion syndrome (56%)
      or selective intrauterine growth restriction (44%). CONCLUSIONS: Our data suggest
      that patients with confirmed twin-twin transfusion syndrome are referred with
      advanced stages of disease (69% stages III-V), with 59% of referrals made after
      20 weeks' gestation. Such a referral pattern calls into question the current
      frequency of sonographic surveillance used by many obstetricians. Revisions of
      current practice guidelines emphasizing the importance of more frequent
      examinations in monochorionic twin gestations beginning at 16 weeks' gestation
      should be considered.

PMID- 22644692
TI  - Fetal hydronephrosis as a predictor of neonatal urologic outcomes.
AB  - OBJECTIVES: The ability to predict surgically relevant fetal renal hydronephrosis
      is limited. We sought to determine the most efficacious second- and third
      trimester fetal renal pelvis anteroposterior diameter cutoffs to predict the need
      for postnatal surgery. METHODS: We retrospectively reviewed the medical records
      of mothers and neonates who had a prenatal sonographic examination in our
      Perinatal-Pediatric Urology Clinic and received follow-up care. Hydronephrosis
      was defined as a renal pelvis anteroposterior diameter of 5 mm or greater in the
      second trimester and 7 mm or greater in the third trimester. Hydronephrosis was
      subdivided into mild, moderate, and severe. RESULTS: Of 8453 fetuses, 96 met the
      criteria and were referred to our clinic. Isolated hydronephrosis was diagnosed
      in 74 fetuses, of which 53 received postnatal follow-up evaluations. The areas
      under the receiver operating characteristic curves for predicting postnatal
      surgery in the second and third trimesters were 0.770 and 0.899, respectively.
      The second-trimester renal anteroposterior diameter threshold that best predicted
      post-natal surgery was 9.5 mm (sensitivity, 71.4%; specificity, 81.1%). The third
      trimester threshold that best predicted postnatal surgery was 15.0 mm
      (sensitivity, 85.7%; specificity, 94.6%). CONCLUSIONS: The fetal renal
      anteroposterior diameter on second- and third-trimester sonography is predictive
      of an increased risk for neonatal urologic surgery. Surgical risk is best
      predicted by a third-trimester renal anteroposterior diameter threshold of 15 mm.

PMID- 22644693
TI  - Feasibility of measuring 3-dimensional renal parenchymal volume to predict
      postnatal renal function in near-term fetuses with congenital hydronephrosis: a
      preliminary study.
AB  - OBJECTIVES: The purposes of this study were to evaluate the feasibility of
      predicting kidney function using the fetal renal parenchymal volume as determined
      by prenatal 3-dimensional (3D) sonography and to determine the association among
      the prenatal renal pelvic diameter, renal parenchymal volume, and postnatal renal
      function in near-term fetuses with unilateral hydronephrosis. METHODS: This
      retrospective study included 42 kidneys (21 normal and 21 hydronephrotic) from 21
      fetuses between 30 and 39 weeks' gestation. We used the extended imaging virtual
      organ computer-aided analysis (XI VOCAL; 10 planes) technique for the prenatal
      volumetric measurements, and postnatal renal function was estimated using renal
      scintigraphy. An independent-samples Student ttest, Spearman's rank correlation,
      and simple linear regression were used for the statistical analyses.
      Reproducibility was confirmed with a paired Student t test and intraclass
      correlation coefficients. RESULTS: The renal pelvic diameter correlated well with
      the renal parenchymal volume Spearman rho = 0.765; P < .001). The postnatal renal
      function correlated with the adjusted 3D renal parenchymal volume (Spearman rho =
      -0.321; P = .043) but did not correlate with the prenatal renal pelvic diameter
      (Spearman rho = -0.291; P = .062). CONCLUSIONS: This preliminary study showed
      that 3D renal parenchymal volume could be a coparameter for predicting postnatal
      renal function with the renal pelvic diameter. Further studies in a larger
      population are required to obtain robust results.

PMID- 22644694
TI  - Antenatal diagnosis of velamentous cord insertion and vasa previa: preparing for
      a good outcome when the cervix is shortened.

PMID- 22644695
TI  - Prenatal hemodynamic assessment of dicephalus twins: sonographic-pathologic
      correlation.

PMID- 22644696
TI  - Double-outlet left ventricle in association with heterotaxy and left isomerism of
      the atrial appendages.

PMID- 22644697
TI  - Sonographic-pathologic correlation of epididymal changes in a suspected case of
      postvasectomy pain syndrome.

PMID- 22644698
TI  - The use of omega-3 poly-unsaturated fatty acids in heart failure: a preferential
      role in patients with diabetes.
AB  - PURPOSE: To review the evidence for a beneficial effect of omega-3 PUFAs in heart
      failure (HF) and its co-morbidities, their possible preferential effect in
      diabetes and the potential mechanism for their benefit. METHODS: We summarize the
      clinical studies which investigated the use of omega-3 PUFAs in patients with HF
      with an emphasis on diabetes. We briefly summarize the evidence for an effect of
      omega-3 PUFAs in patients with coronary artery disease (CAD), atrial fibrillation
      (AF) and ventricular arrhythmias. We also discuss the proposed mechanisms of
      omega-3 PUFA action in cardiovascular diseases. RESULTS: While there is emerging
      evidence for a beneficial effect of omega-3 PUFA supplementation in patients with
      HF, the evidence for other indications have been variable and conflicting. In HF
      patients with diabetes, omega-3 PUFAs may have a preferential therapeutic
      benefit. Randomized controlled trials did not show considerable beneficial
      effects of omega-3 PUFAs in other conditions such as CAD and AF. In a diabetic
      and insulin-resistant state, omega-3 PUFAs bind to the G-protein coupled
      receptor, GPR120, resulting in reduced cytokine production from inflammatory
      macrophages and improved signaling in adipocytes, leading to a reduction in
      insulin resistance. CONCLUSIONS: There is promising evidence showing that use of
      omega-3 PUFA supplementation improves clinical outcomes of HF patients with
      diabetes. Further clinical trials are needed in this regard.

PMID- 22644699
TI  - Clar's aromatic sextet and pi-electron distribution in nanographene.
AB  - Cut into pieces: The pi-electron distribution in nanographene fragments isolated
      between oxidized graphene areas is investigated using scanning probe microscopy
      (see picture). The edge-shape-dependent localization and migration of the Clar
      sextet explains the observed pi-state distributions and enables investigation of
      the electronic properties.

PMID- 22644700
TI  - Bioorthogonal imaging of aurora kinase A in live cells.

PMID- 22644701
TI  - Glucocorticoid receptor-mediated transcriptional regulation of N
      acetyltransferase 1 gene through distal promoter.
AB  - Human arylamine N-acetyltransferase 1, (HUMAN)NAT1, is a phase II xenobiotic
      metabolizing enzyme that plays an important role in drug and carcinogen
      biotransformation and cancer development. Its gene expression has been shown to
      be regulated by environmental factors. The purpose of the current study is to
      determine the involvement of nuclear receptors in transcriptional regulation of
      (HUMAN)NAT1 gene. We show that among the nuclear receptors examined, including
      the glucocorticoid receptor, retinoid acid receptor-related orphan receptor
      alpha, constitutive androstane receptor, pregnane X receptor, aryl hydrocarbon
      receptor, and retinoic acid receptor, the glucocorticoid receptor plays a
      dominant role in regulating (HUMAN)NAT1 gene expression through distal promoter
      (P3). The involvement of the glucocorticoid receptor in transcription regulation
      of (HUMAN)NAT1 gene expression was demonstrated by dexamethasone treatment,
      reporter assay using plasmid-containing 3 kbp of 5'-end region of promoter 3, and
      treatment of anti-glucocorticoid RU486 in primary culture of human hepatocytes
      and transfected HepG2 cells. In addition, translation inhibition did not affect
      dexamethasone-induced gene expression through P3, suggesting that dexamethasone
      effect is directly mediated by glucocorticoid receptor activation. Furthermore,
      deletion analysis revealed the presence of multiple responsive elements within
      the 3 kbp fragment of P3. Transfection assays in mice using hydrodynamics-based
      procedure and reporter gene assay in a mouse cell line revealed that
      glucocorticoid-induced NAT gene expression is species dependent. Dexamethasone
      treatment of transfected mice and mouse cell line decreased (MOUSE)Nat2 gene
      expression, (HUMAN)NAT1 homologue. These results suggest that glucocorticoids
      serve as a modulator for (HUMAN)NAT1 gene expression via the P3-containing 5'
      flanking region.

PMID- 22644702
TI  - The use of modeling tools to drive efficient oral product design.
AB  - Modeling and simulation of drug dissolution and oral absorption has been
      increasingly used over the last decade to understand drug behavior in vivo based
      on the physicochemical properties of Active Pharmaceutical Ingredients (API) and
      dosage forms. As in silico and in vitro tools become more sophisticated and our
      knowledge of physiological processes has grown, model simulations can provide a
      valuable confluence, tying-in in vitro data with in vivo data while offering
      mechanistic insights into clinical performance. To a formulation scientist, this
      unveils not just the parameters that are predicted to significantly impact
      dissolution/absorption, but helps probe explanations around drug product
      performance and address specific in vivo mechanisms. In formulation, development,
      in silico dissolution-absorption modeling can be effectively used to guide: API
      selection (form comparison and particle size properties), influence clinical
      study design, assess dosage form performance, guide strategy for dosage form
      design, and breakdown clinically relevant conditions on dosage form performance
      (pH effect for patients on pH-elevating treatments, and food effect). This
      minireview describes examples of these applications in guiding product
      development including those with strategies to mitigate observed clinical
      exposure liability or mechanistically probe product in vivo performance
      attributes.

PMID- 22644703
TI  - The effect of sterilization on the mechanical properties of intact rabbit humeri
      in three-point bending, four-point bending and torsion.
AB  - Load bearing bone allografts are used to replace the mechanical function of bone
      that has been removed or to augment bone that has been damaged in trauma. In
      order to minimize the risk of infection and immune response, the bone is
      delipidated and terminally sterilized prior to implantation. The optimal method
      for bone graft sterilization has been the topic of considerable research.
      Recently, supercritical carbon dioxide (SCCO(2)) treatments have been shown to
      terminally sterilize bone against a range of bacteria and viruses. This study
      aimed to evaluate the effect of SCCO(2) treatment compared with two doses of
      gamma irradiation, on the mechanical properties of whole bone. Paired rabbit
      humeri were dissected and randomly assigned into either SCCO(2) control, SCCO(2)
      additive or gamma irradiation at 10 or 25 kGy treatment groups. The bones were
      mechanically tested in three-point and four-point bending and torsion, with the
      lefts acting as controls for the treated rights. Maximum load, energy to failure
      and stiffness were evaluated. This study found that SCCO(2) treatment with or
      without additive did not alter maximum load, energy to failure or stiffness
      significantly under any loading modality. Gamma irradiation had a deleterious
      dose dependant effect, with statistically significant decreases in all mechanical
      tests at 25 kGy; while at 10 kGy there were reductions in all loading profiles,
      though only reaching statistical significance in torsion. This study highlights
      the expediency of SCCO(2) treatment for bone allograft processing as terminal
      sterilization can be achieved while maintaining the intrinsic mechanical
      properties of the graft.

PMID- 22644704
TI  - Mechanism and stem-cell activity of 5-carboxycytosine decarboxylation determined
      by isotope tracing.
AB  - Eraserhead: Stem cells seem to erase epigenetic information by decarboxylation of
      the newly discovered epigenetic base 5-carboxycytosine (caC; see picture). This
      reaction is likely to involve a nucleophilic attack of the C5-C6 double bond.

PMID- 22644705
TI  - Highly stereoselective synthesis of alpha-alkyl-alpha-hydroxycarboxylic acid
      derivatives catalyzed by a dinuclear zinc complex.
AB  - A dinuclear zinc-ProPhenol catalyst enables highly enantioselective nitro-Michael
      reactions with oxazol-4(5H)-ones as nucleophilic substrates (see scheme, Nap = 2
      naphthyl). This work highlights the utility of the ProPhenol family of ligands.
      The modular nature of these ligands proved crucial in the optimization of
      reaction conditions to achieve excellent stereoselectivities.

PMID- 22644706
TI  - Investigation of formulation variables and excipient interaction on the
      production of niosomes.
AB  - The aim of this study was to investigate the effects of formulation and process
      variables on the properties of niosomes formed from Span 40 as nonionic
      surfactant. A variety of formulations encapsulating Paclitaxel, a hydrophobic
      model drug, were prepared using different dicetyl phosphate (DCP) and Span 40
      cholesterol (1:1) amounts. Formulations were optimized by multiple regression
      analysis to evaluate the changes on niosome characteristics such as entrapment
      efficiency, particle size, polydispersity index, zeta potential and in vitro drug
      release. Multiple regression analysis revealed that as Span 40-cholesterol
      amounts in the formulations were increased, zeta potential and percent of drug
      released at 24th hour were decreased. Besides, DCP was found to be effective on
      increasing niosome size. As a process variable, the effect of sonication was
      observed and findings revealed an irreversible size reduction on Span 40 niosomes
      after probe sonication. Monodisperse small sized (133 +/- 6.01 nm) Span 40
      niosomes entrapping 98.2% of Paclitaxel with a weight percentage of 3.64% were
      successfully prepared. The drug-excipient interactions in niosomes were observed
      by differential scanning calorimetry and X-ray powder diffraction analysis. Both
      techniques suggest the conversion of PCTs' crystal structure to amorphous form.
      The thermal analyses demonstrate the high interaction between drug and surfactant
      that explains high entrapment efficiency. After 3-month storage, niosomes
      preserved their stability in terms of drug amount and particle size. Overall,
      this study showed that Span 40 niosomes with desired properties can be prepared
      by changing the content and production variables.

PMID- 22644707
TI  - Preparation and in vitro aerosol performance of spray-dried Shuang-Huang-Lian
      corrugated particles in carrier-based dry powder inhalers.
AB  - The development of dry powder inhalation (DPI) products of traditional Chinese
      medicine (TCM) remains to be a challenge due to chemical complexity and batch-to
      batch variations in constituent composition. This study was to investigate the
      feasibility of using spray-dried corrugated particles to improve the aerodynamic
      performance of a TCM, Shuang-Huang-Lian (SHL), in carrier-based DPI. Particles
      with different surface roughness were spray-dried by the addition of leucine and
      concomitant manipulation of spray-drying parameters. The surface roughness was
      determined by atomic force microscopy, whilst the aerodynamic performance of drug
      particle-mannitol/lactose blends was evaluated using a next-generation
      pharmaceutical impactor through a Cyclohaler. Although the emission efficiency
      for corrugated particle-based DPI was ~10% lower than that for smooth SHL, the
      fine particle fractions (FPF(<4.4 MUm)) of 32.4-36.8% for the former were
      significantly higher than those of 14.7-16.2% for the latter. In particular, the
      FPF and fraction of drug detached from the carrier appeared not to be
      significantly affected by the variation in constituent composition of SHL. This
      study demonstrates that the use of corrugated particles in carrier-based DPI
      improved aerosol performance by facilitating drug detachment from the carrier,
      independent of variation in constituent composition, and such particles were
      potentially applicable to the development of SHL DPI products.

PMID- 22644708
TI  - Insulin-loaded pH-sensitive hyaluronic acid nanoparticles enhance transcellular
      delivery.
AB  - In the present study, we developed novel insulin-loaded hyaluronic acid (HA)
      nanoparticles for insulin delivery. The insulin-loaded HA nanoparticles were
      prepared by reverse-emulsion-freeze-drying method. This method led to a
      homogenous population of small HA nanoparticles with average size of 182.2 nm and
      achieved high insulin entrapment efficiencies (approximately 95%). The pH
      sensitive HA nanoparticles as an oral delivery carrier showed advantages in
      protecting insulin against the strongly acidic environment of the stomach, and
      not destroying the junction integrity of epithelial cells which promise long-term
      safety for chronic insulin treatment. The results of transport experiments
      suggested that insulin-loaded HA nanoparticles were transported across Caco-2
      cell monolayers mainly via transcellular pathway and their apparent permeability
      coefficient from apical to basolateral had more than twofold increase compared
      with insulin solution. The efflux ratio of P (app) (B to A) to P (app) (A to B)
      less than 1 demonstrated that HA nanoparticle-mediated transport of insulin
      across Caco-2 cell monolayers underwent active transport. The results of
      permeability through the rat small intestine confirmed that HA nanoparticles
      significantly enhanced insulin transport through the duodenum and ileum. Diabetic
      rats treated with oral insulin-loaded HA nanoparticles also showed stronger
      hypoglycemic effects than insulin solution. Therefore, these HA nanoparticles
      could be a promising candidate for oral insulin delivery.

PMID- 22644709
TI  - A cremophor-free self-microemulsified delivery system for intravenous injection
      of teniposide: evaluation in vitro and in vivo.
AB  - In order to tackle the problems on low water solubility of teniposide,
      involvement of toxic surfactant in its injection, and the poor stability during
      infusion, a Cremophor-free teniposide self-microemulsified drug delivery system
      (TEN-SMEDDS) was prepared for the first time, characterized, and evaluated in
      comparison with teniposide injection (VUMON) in vitro and in vivo. The optimized
      formulation contained N, N-dimethylacetamide, medium-chain triglyceride,
      lecithin, and dehydrated alcohol besides teniposide. The TEN-SMEDDS could form
      fine droplets with mean diameter of 282 +/- 21 nm and zeta potential of -7.5 +/-
      1.7 mV after dilution with 5% glucose, which were stable within 4 h. The release
      of teniposide from TEN-SMEDDS and VUMON was similar. However, the pharmacokinetic
      behavior of TEN-SMEDDS in rats was different from that of VUMON, evidenced by the
      lower area under the concentration-time curve and larger volume of distribution
      in emulsion group. Finally, TEN-SMEDDS was found to distribute more teniposide in
      most tissues, especially in reticuloendothelial system, after intravenous
      administration to rats. Importantly, brain drug level in TEN-SMEDDS group was
      higher than or similar to that in control group, although the emulsion system had
      a lower plasma drug concentration. In conclusion, the novel SMEDDS prepared here,
      without toxic surfactant and as an oil solution before use, may be potential for
      clinical use due to its low toxicity and high store stability. It may be
      favorable for the treatment of some tumors like cerebroma, since it may achieve
      the relatively higher drug level in brain but lower blood concentration.

PMID- 22644710
TI  - Comment on Hsiao et al.: Correlation of early-phase 18F-florbetapir (AV
      45/Amyvid) PET images to FDG images: preliminary studies.

PMID- 22644712
TI  - Comment on Pepe et al.: somatostatin receptor SPECT.

PMID- 22644713
TI  - The role of early 18F-FDG PET/CT in prediction of progression-free survival after
      90Y radioembolization: comparison with RECIST and tumour density criteria.
AB  - PURPOSE: This study evaluated the ability of (18)F-FDG PET/CT imaging to predict
      early response to (90)Y-radioembolization in comparison with contrast-enhanced CT
      (CECT) using RECIST and lesion density (Choi) criteria. Progression-free survival
      (PFS) in patients with liver metastases at 2 years and decline in tumour markers
      were the primary end-points of the study. METHODS: A total of 121 liver lesions
      were evaluated in 25 patients (14 men, 11 women) with liver-dominant metastatic
      colorectal cancer who underwent (18)F-FDG PET/CT and CECT before and 6-8 weeks
      after treatment. Changes in SUV(max), tumour density measured in terms of
      Hounsfield units and the sum of the longest diameters (LD) were calculated for
      the target liver lesions in each patient. The patient responses to treatment were
      categorized using EORTC PET criteria, tumour density criteria (Hounsfield units)
      and RECIST, and were correlated with the responses of tumour markers and 2-year
      PFS using Kaplan-Meier plots and the log-rank test for comparison. Multivariate
      proportional hazards (Cox) regression analysis was performed to assess the effect
      of relevant prognostic factors on PFS. RESULTS: Using (18)F-FDG PET/CT response
      criteria, 15 patients had a partial response (PR) and 10 patients had stable
      disease (SD), while using RECIST only 2 patients had a PR and 23 had SD. Two
      patients had a PR, 21 SD and 2 progressive disease using tumour density criteria.
      The mean changes in SUV(max), sum of the LDs and tumour density after treatment
      were 2.9 +/- 2.6, 7.3 +/- 14.4 mm and 1.9 +/- 13.18 HU, respectively. Patients
      who had a PR on (18)F-FDG PET/CT had a mean decrease of 44.5 % in SUV(max)
      compared to those with SD who had a decrease of only 10.3 %. The decreases in
      SUV(max) and sum of the LDs were significant (p < 0.0001, p < 0.05, respectively)
      while the decrease in tumour density was not (p > 0.1065). The responses on the
      (18)F-FDG PET/CT studies were highly correlated with the responses of tumour
      markers (p < 0.0001 for LDH, p = 0.01 for CEA and p = 0.02 for Ca19-9), while the
      responses on the CECT studies using both RECIST and tumour density criteria were
      not significantly correlated with the responses of tumour markers. The responses
      on (18)F-FDG PET/CT studies also significantly predicted PFS (the median PFS in
      those with a PR was 12.0 months and in those with SD was 5 months, p < 0.0001),
      while RECIST and tumour density did not significantly predict PFS. Multivariate
      analysis demonstrated that responses on (18)F-FDG PET/CT studies and decreases in
      SUV(max) of <= 2.0 were the strongest predictors of PFS. CONCLUSION: Early
      response assessment to (90)Y-radioembolization using (18)F-FDG PET/CT is superior
      to RECIST and tumour density, demonstrating a correlation with tumour markers and
      significantly predicting PFS in patients with liver metastases. This could enable
      early response-adapted treatment strategies to be employed.

PMID- 22644715
TI  - Toward tailored medicine (and beyond): the phaeochromocytoma and paraganglioma
      model.

PMID- 22644714
TI  - iRENEX: a clinically informed decision support system for the interpretation of
      99mTc-MAG3 scans to detect renal obstruction.
AB  - PURPOSE: Decision support systems for imaging analysis and interpretation are
      rapidly being developed and will have an increasing impact on the practice of
      medicine. RENEX is a renal expert system to assist physicians evaluate suspected
      obstruction in patients undergoing mercaptoacetyltriglycine (MAG3) renography.
      RENEX uses quantitative parameters extracted from the dynamic renal scan data
      using QuantEMTMII and heuristic rules in the form of a knowledge base gleaned
      from experts to determine if a kidney is obstructed; however, RENEX does not have
      access to and could not consider the clinical information available to
      diagnosticians interpreting these studies. We designed and implemented a
      methodology to incorporate clinical information into RENEX, implemented motion
      detection and evaluated this new comprehensive system (iRENEX) in a pilot group
      of 51 renal patients. METHODS: To reach a conclusion as to whether a kidney is
      obstructed, 56 new clinical rules were added to the previously reported 60 rules
      used to interpret quantitative MAG3 parameters. All the clinical rules were
      implemented after iRENEX reached a conclusion on obstruction based on the
      quantitative MAG3 parameters, and the evidence of obstruction was then modified
      by the new clinical rules. iRENEX consisted of a library to translate parameter
      values to certainty factors, a knowledge base with 116 heuristic interpretation
      rules, a forward chaining inference engine to determine obstruction and a
      justification engine. A clinical database was developed containing patient
      histories and imaging report data obtained from the hospital information system
      associated with the pertinent MAG3 studies. The system was fine-tuned and tested
      using a pilot group of 51 patients (21 men, mean age 58.2 +/- 17.1 years, 100
      kidneys) deemed by an expert panel to have 61 unobstructed and 39 obstructed
      kidneys. RESULTS: iRENEX, using only quantitative MAG3 data agreed with the
      expert panel in 87 % (34/39) of obstructed and 90 % (55/61) of unobstructed
      kidneys. iRENEX, using both quantitative and clinical data agreed with the expert
      panel in 95 % (37/39) of obstructed and 92 % (56/61) of unobstructed kidneys. The
      clinical information significantly (p < 0.001) increased iRENEX certainty in
      detecting obstruction over using the quantitative data alone. CONCLUSION: Our
      renal expert system for detecting renal obstruction has been substantially
      expanded to incorporate the clinical information available to physicians as well
      as advanced quality control features and was shown to interpret renal studies in
      a pilot group at a standardized expert level. These encouraging results warrant a
      prospective study in a large population of patients with and without renal
      obstruction to establish the diagnostic performance of iRENEX.

PMID- 22644716
TI  - Simulated comparison of topical and oral formulations of 5-aminosalicylate for
      the treatment of ulcerative colitis.
AB  - BACKGROUND: 5-Aminosalicylate (5-ASA) formulations are approved for the treatment
      of ulcerative colitis (UC). Determination of the colonic pharmacokinetics of 5
      ASA is challenging. A dynamic model of 5-ASA colonic amounts after oral delayed
      release 5-ASA (Asacol), oral extended delayed-release 5-ASA (Lialda), 5-ASA enema
      (Rowasa), foam and suppositories (Canasa) was developed to determine the colonic
      kinetics of these agents. METHODS: We created a model with Stella software.
      Colonic 5-ASA in the right, transverse, descending, sigmoid colon, and rectum
      were estimated for adults after recommended doses of the above formulations.
      Simulations of active mild/moderate UC and in remission were performed and
      compared using Student's t-test for differences in means. RESULTS: For UC in
      remission, the highest amounts of 5-ASA were from Asacol in the right and
      transverse colon (P < 0.01), Lialda in the descending and sigmoid colon (P <
      0.01), and Rowasa in the rectum (P < 0.01). For active UC, sigmoid amounts were
      highest with foam (P < 0.01), and rectal amounts highest with Rowasa (P < 0.01).
      Differences in rectosigmoid amounts of 5-ASA from enemas and suppositories for UC
      in remission occurred based on the relationship between the timing of
      administration relative to the daily bowel movement (P < 0.01). CONCLUSIONS:
      Compared to Asacol, Lialda results in higher 5-ASA amounts in the left colon.
      Asacol with Rowasa provides highest 5-ASA amounts across the entire colon. Higher
      5-ASA amounts from topical formulations occur when the insertion occurs soon
      after the daily bowel movement. This model provides a rationale for further
      investigation.

PMID- 22644717
TI  - Single port-assisted fully laparoscopic abdominoperineal resection (APR) with
      immediate V-RAM flap reconstruction of the perineal defect.
AB  - Abdominoperineal resection (APR) of anorectal cancers after neoadjuvant
      chemoradiotherapy may incur significant perineal morbidity. While vertical rectus
      abdominis muscle (V-RAM) flaps can fill the pelvic resection space with health
      tissue, their use has previously been described predominantly in association with
      laparotomy. Here, we describe a means of combination laparoscopic APR with V-RAM
      flap reconstruction that allows structural preservation of the entire abdominal
      wall throughout the oncological resection and of the deep parietal layers after V
      RAM donation. Furthermore, a single port access device used at the end colostomy
      site allows a second senior surgeon assist with an additional two working
      instruments for the purpose of improved pelvic tissue retraction, especially
      useful in obese patients.

PMID- 22644718
TI  - A hybrid single-trocar VATS technique for extracorporeal wedge biopsy of the
      lingula in patients with diffuse lung disease.
AB  - Lung biopsy is the last option to obtain lung tissue for a precise diagnosis in
      patients with interstitial lung disease (ILD). Several surgical techniques have
      been reported. The successful application of a hybrid approach is herein
      reported. The procedure utilizes a single-trocar video-assisted thoracoscopic
      surgery technique to localize and withdraw the tip of the lingula outside the
      chest to perform a biopsy in the diagnosis of ILDs. The advantages of this
      technique over other commonly used methods have also been discussed.

PMID- 22644719
TI  - Dabigatran and left atrial appendage thrombus.
AB  - A 59-year-old white woman with previous history of arterial hypertension
      consulted because of palpitations. Atrial fibrillation of uncertain duration was
      diagnosed. She was not receiving anticoagulants. A trans-esophageal
      echocardiogram was performed, and a large left atrial appendage thrombus was
      detected. A strategy of rate control and anti-vitamin K treatment was started. On
      the subsequent days, we could not reach therapeutic INRs. Therefore, it was
      decided to stop warfarin and initiate dabigatran. We describe the evolution of
      the patient, the thrombus resolution, and a successful electrical cardioversion.
      In our comments, we summarize the natural history of left atrial thrombus, both
      with and without anticoagulant therapy. We also discuss the differences between
      warfarin and dabigatran.

PMID- 22644720
TI  - Paradoxical thrombosis, part 2: anticoagulant and antiplatelet therapy.
AB  - Arterial thrombosis is the leading causes of morbidity and mortality worldwide,
      whereas venous thrombosis is the most common preventable cause of hospital death.
      In either case, venous and arterial thrombosis should be considered autonomous
      entities, with only minor overlaps in terms of risk factors, predisposing
      conditions and pathogenesis. Besides the widespread perception of embolization
      originating from low-pressure venous system and triggering ischemic stroke or
      peripheral arterial occlusion, "paradoxical" thrombosis might also develop or
      occur within clinical or biological circumstances where the blood should be less
      predisposed to clot, and wherein this risk is mostly unpredictable or overlooked.
      In this article we review epidemiological evidence and potential pathogenetic
      mechanisms of paradoxical thrombosis developing during antithrombotic therapy
      with vitamin K antagonists and heparin (i.e. heparin-induced thrombocytopenia),
      or antiplatelet agents such as aspirin, glycoprotein IIb/IIIa inhibitors or
      clopidogrel, and mostly attributable to direct effect of the agent.

PMID- 22644721
TI  - PAR-1 antagonists: current state of evidence.
AB  - Vorapaxar (SCH 530348) and atopaxar (E5555) are oral protease-activated receptor
      1 (PAR-1) antagonists with high bioavailability. They inhibits thrombin induced
      platelet aggregation by competitively inhibiting PAR-1. We systematically
      evaluated the evidence for the efficacy and safety of all PAR-1 antagonists as
      well as for the individual drugs vorapaxar and atopaxar in different databases
      PubMed, EMBASE, Scopus, and Cochrane register of Controlled Clinical Trials
      (CENTRAL).We selected randomized controlled trials of PAR-1 antagonists that
      reported on cardiovascular mortality as a clinical outcome. The random-effects
      Mantel-Haenszel model was used to evaluate the effect of PAR-1 antagonists on
      cardiovascular mortality. Seven trials were selected (N = 42,355) for analysis.
      PAR-1 antagonists as a class, as well as individually, were associated with a non
      significant numerically lower risk of cardiovascular mortality than that seen
      with agents used in the control group; RR, 0.93; 95% CI, 0.83-1.04; P = 0.20). No
      heterogeneity was noted. However, PAR-1 antagonists also appeared to increase the
      risk of bleeding significantly. PAR-1 antagonists appear to be associated with
      some reduction in the risk of cardiovascular mortality; however the significantly
      higher bleeding risk noted with PAR-1 antagonists appear to mandate a very
      careful selection of patients that may benefit without a substantially increased
      risk of bleeds.

PMID- 22644722
TI  - Paradoxical thrombosis part 1: factor replacement therapy, inherited clotting
      factor deficiencies and prolonged APTT.
AB  - The pathogenesis of venous and arterial thrombosis is complex and multifaceted,
      entailing a multitude of risk factors, which only marginally overlap between the
      two vessels districts. Along with conventional and universally recognized risk
      factors, thrombosis might also develop as a consequence of unusual, atypical,
      unsuspected and even paradoxical conditions. Although the term "paradoxical
      embolism" is typically used to identify an embolization process that originates
      from the low-pressure venous system and may generate ischemic stroke or
      peripheral arterial occlusion through a cardiac or pulmonary shunt, there are
      additional clinical circumstances whereby the risk of thrombosis is surprising,
      unpredicted or even neglected. In this article we thereby analyze the prevalence,
      as well as the pathogenesis, of thrombosis associated with apparently paradoxical
      triggers such as during factor replacement therapy in haemophiliacs or in
      patients with von Willebrand disease; in patients with inherited clotting factor
      deficiencies especially involving factor XII, factor VII, fibrinogen; or in those
      with a prolonged activated partial thromboplastin time for the presence of lupus
      anticoagulant.

PMID- 22644725
TI  - Enantioselective total synthesis of marine diterpenoid clavulactone.
AB  - The key steps in the synthesis of clavulactone are formation of an enantiopure
      cyclopentane precursor by epoxide rearrangement and intramolecular carbonyl-ene
      reaction, construction of the 3,4-dihydro-2H-pyran ring by intermolecular hetero
      Diels-Alder reaction, closure of the eleven-membered ring, and finally generation
      of the lactone functionality by chemoselective allylic C(sp(3))-H oxidation.

PMID- 22644723
TI  - What do we know and we do not know about cardiovascular autonomic neuropathy in
      diabetes.
AB  - Cardiovascular autonomic neuropathy (CAN) in diabetes is generally overlooked in
      practice, although awareness of its serious consequences is emerging. Challenges
      in understanding the complex, dynamic changes in the modulation of the
      sympathetic/parasympathetic systems' tone and their interactions with physiologic
      mechanisms regulating the control of heart rate, blood pressure, and other
      cardiovascular functions in the presence of acute hyper-or-hypoglycemic stress,
      other stressors or medication, and challenges with sensitive evaluations have
      contributed to lower CAN visibility compared with other diabetes complications.
      Yet, CAN is a significant cause of morbidity and mortality, due to a high-risk of
      cardiac arrhythmias, silent myocardial ischemia and sudden death. While striving
      for aggressive risk factor control in diabetes practice seemed intuitive, recent
      reports of major clinical trials undermine established thinking concerning
      glycemic control and cardiovascular risk. This review covers current
      understanding and gaps in that understanding of the clinical implications of CAN
      and prevention and treatment of CAN.

PMID- 22644726
TI  - Complications of oncologic therapy in the abdomen and pelvis: a review.
AB  - Cancer therapy has significantly improved in the past few decades with
      development of various newer classes of cytotoxic chemotherapy as well as novel,
      molecularly targeted chemotherapy. Similar to chemotherapy, radiotherapy is
      another important therapeutic option used in the curative and palliative
      management of various abdominal malignancies. However, both these treatments
      affect the tumor as well as the normal tissues, leading to significant toxicity.
      These side effects range from mild to life threatening, and may involve multiple
      organs. Imaging plays an important role in the early identification of such
      complications, which may allow more effective patient management. The aim of this
      article is to discuss and illustrate the wide spectrum of chemotherapy and
      radiotherapy induced complications in the abdomen and pelvis.

PMID- 22644724
TI  - The vascular stem cell niche.
AB  - Stem cells in adult organs reside in specialized niches that regulate their
      proliferation and differentiation. Investigations during the last few years have
      unveiled a regulatory role for blood vessels in these microenvironments.
      Mesenchymal stem cells (MSCs) are located surrounding capillaries in a variety of
      tissues and have the capacity to differentiate into different mesodermal
      lineages. Angiogenic progenitor cells have also been found in the adventitial
      layer of large vessels. In the bone marrow, endothelial cells control
      hematopoietic stem cell (HSC) release, and in the brain, blood vessels regulate
      neural stem cell (NSC) self-renewal and neurogenesis. Similarly, perivascular
      progenitor cells have also been found in the heart. This intimate connection
      between stem cells and the vasculature contributes to tissue homeostasis and
      repair. In this review, we focus on the regulation of stem and progenitor cells
      in different adult niches by blood vessels and the few mechanisms that are known
      to mediate this interaction.

PMID- 22644727
TI  - Identification and molecular characterisation of HMW glutenin subunit 1By16* in
      wild emmer.
AB  - In this study, a novel y-type high molecular weight glutenin subunit (HMW-GS) in
      wild emmer wheat Triticum turgidum L. var. dicoccoides (Korn.) accession KU1952
      was identified by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS
      PAGE), capillary electrophoresis (CE) and matrix-assisted laser desorption
      ionisation/time-of-flight/mass spectrometry (MALDI-TOF-MS). Its electrophoretic
      mobility and molecular weight were similar to those of 1By16 and was designated
      as 1By16*. The complete coding sequence of the 1By16* gene isolated by allelic
      specific polymerase chain reaction (AS-PCR) consists of 2,157 bp, encoding 729
      amino acid residues. The real presence and authenticity of the 1By16* gene in
      KU1952 were further confirmed by liquid chromatography-tandem mass spectrometry
      (LC-MS/MS), heterologous expression and Western blotting. The molecular structure
      as well as phylogenetic analysis revealed that 1By16* had 21 single-nucleotide
      polymorphism (SNP) variations and possessed greater similarity with superior
      quality subunits 1By15 and 1By16 of common wheat. Secondary structure prediction
      displayed higher alpha-helix and beta-strand contents in the 1By16* subunit,
      which could form a superior gluten structure and, consequently, might have
      positive effects on dough quality. Our results suggest that 1By16* is expected to
      be a new potential gene for wheat quality improvement.

PMID- 22644728
TI  - Brain metastases in patients under 50 years of age: retrospective analysis.
AB  - Several previous publications suggested that younger patients with brain
      metastases have longer survival than older patients. However, detailed studies of
      younger patient groups are scarce. Therefore, a multi-institutional analysis of
      younger patients with brain metastases was performed (defined as adults with age
      <50 years). Prognostic factors for survival were examined by uni- and
      multivariate analyses and compared to those obtained in patients with age >=50
      years. Multivariate analysis of 106 patients (median age 44 years, range 23-49
      years) revealed three independent prognostic factors for survival: performance
      status, extracranial metastases and primary tumor control. Survival was
      significantly better in patients treated after the year 2000 (median 9.4 months)
      as compared to those treated before the year 2000 (median 5.1 months, p = 0.04).
      This improvement appeared to be related to an increased use of surgery or
      radiosurgery (SRS) and decreasing numbers of patients with uncontrolled primary
      tumor. Irrespective of management approach, survival beyond 5 years was uncommon
      (actuarial rate 6 %; 17 % in patients treated with upfront surgery or SRS). In
      conclusion, more intense multidisciplinary approaches aiming at control both in
      the brain, extracranial metastatic sites, and primary tumor site might have
      contributed to gradual survival improvements in recent years. Nevertheless,
      further efforts are necessary to improve long-term survival.

PMID- 22644730
TI  - Effect of hygiene and medication on preweaning survival and growth of Djallonke
      sheep in Atacora, Benin.
AB  - Low sheep productivity in North Benin hampers economic development, and
      improvement can contribute to reduction of rural poverty and food insecurity. To
      reduce one of the constraints to the productivity of Djallonke sheep, high
      mortality during suckling in full rainy and start dry season, we tested hygienic
      measures and medication in improved housing. The effect of the two treatments and
      their combination on lamb performance and the internal rate of return (IRR) were
      compared to a control. For each treatment, survival and growth were observed in
      20 lambs, living in 38 herds. Good housing and hygiene (daily cleaning and
      fortnightly disinfection of stable and water and feed troughs) reduced mortality
      and increased growth of suckling lambs until 3 months. Good housing plus
      medication (unique injection of vitamins and amino acids and with ivermectine for
      deworming, weekly tick treatment by spraying, and in case of diarrhea, antibiotic
      treatment) reduced mortality, but growth was not higher than the control.
      Accounting labor opportunity, the IRR was about equal for both, but capital
      investment was lower for the hygiene treatment which is thus more accessible to
      poor farmers. The combination of both treatments increased growth and benefits
      compared with the hygiene treatment, but decreased the IRR.

PMID- 22644731
TI  - Level and period of realimentation to assess improvement in body condition and
      carcass quality in cull ewes.
AB  - Improvement in body condition was assessed in 40 cull ewes (>6 years), equally
      distributed in two groups and realimented with ad libitum roughage (gram straw)
      and two levels of concentrate feeding, i.e., 2.5 % (T(1)) of live weight (LW) and
      ad libitum (T(2)). Five representative animals from an initial 45 were
      slaughtered at the initiation of the study (0 day) and five animals from each
      treatment at 44, 67, and 90 days of experiment for carcass attributes.
      Improvement in body condition score (BCS), nutrient utilization, feed efficiency,
      and carcass traits were assessed at 44, 67, and 90 days. Metabolism trial of 6
      day collection of feed, feces, and urine samples was conducted on five
      representative ewes from each group after 60 days of feeding. The level of
      concentrate feeding on LW gain and BCS was significant, and the duration of
      realimentation showed a linear improvement (P < 0.001). The digestibility and
      intake of dry matter, organic matter, and crude protein was higher (P < 0.05) in
      T(2). The N intake, absorption, and balance showed a similar trend. Increase (P <
      0.05) in total N, trichloroacetic acid precipitable N, and ammonia N was observed
      with extension of realimentation period. Blood metabolic profile also showed
      improvement (P < 0.05) from an undernourished state to normal after alimentation.
      Animals in T(2) accumulated higher LW with minimal expenditure of metabolizable
      energy (73.4 vs 79.1 MJ) and higher efficiency of feed conversion during 68 to 90
      days of realimentation. Linear improvement (P < 0.01) in carcass traits
      (preslaughter weight, empty live weight, hot carcass weight, dressing percentage,
      and amount of subcutaneous and intramuscular fat) and composition of longissimus
      dorsi muscle was observed. Ad lib concentrate supplementation for a period of 90
      days may thus be considered appropriate for achieving desired efficiency of gain
      and improvement in body condition of cull ewes for quality mutton production.

PMID- 22644732
TI  - Breeding objectives for indigenous chicken: model development and application to
      different production systems.
AB  - A bio-economic model was developed to evaluate the utilisation of indigenous
      chickens (IC) under different production systems accounting for the risk attitude
      of the farmers. The model classified the production systems into three categories
      based on the level of management: free-range system (FRS), where chickens were
      left to scavenge for feed resources with no supplementation and healthcare;
      intensive system (IS), where the chickens were permanently confined and supplied
      with rationed feed and healthcare; and semi-intensive system (SIS), a hybrid of
      FRS and IS, where the chickens were partially confined, supplemented with
      rationed feeds, provided with healthcare and allowed to scavenge within the
      homestead or in runs. The model allows prediction of the live weights and feed
      intake at different stages in the life cycle of the IC and can compute the
      profitability of each production system using both traditional and risk-rated
      profit models. The input parameters used in the model represent a typical IC
      production system in developing countries but are flexible and therefore can be
      modified to suit specific situations and simulate profitability and costs of
      other poultry species production systems. The model has the capability to derive
      the economic values as changes in the genetic merit of the biological parameter
      results in marginal changes in profitability and costs of the production systems.
      The results suggested that utilisation of IC in their current genetic merit and
      production environment is more profitable under FRS and SIS but not economically
      viable under IS.

PMID- 22644733
TI  - Prevalence of Neospora caninum antibodies in dairy cattle and water buffaloes and
      associated abortions in the plateau of Southern Peninsular India.
AB  - A seroprevalence study of bovine neosporosis was conducted among 1,927 dairy
      cattle and 341 water buffaloes from Karnataka and Andhra Pradesh states in
      plateau of southern peninsular India by employing competitive enzyme-linked
      immunosorbent assay. Overall, 12.61 and 9.97 % sera samples were found positive
      for the presence of Neospora caninum antibody, respectively, among cattle and
      water buffaloes. Out of 1,927 sera samples from cattle, 912 and 1,015 samples
      were collected from unorganized and organized herds, respectively. The cattle
      screened were of upgraded Holstein-Friesian and water buffaloes were of graded
      Surti breed. Significantly (p < 0.05) higher prevalence was found in the cattle
      in unorganized herds (16.66 %) in comparison to organized herds (8.96 %). The
      highest seroprevalence was recorded in the age group of 4 years and above in both
      type of cattle herds and water buffaloes. There was a significant variation of
      seroprevalence (p < 0.05) observed between different age groups of cattle. The
      rate of seroprevalence increased with the increment in the age of the animals
      suggesting a possibility of horizontal mode of transmission of the infection from
      the environment. The percentage of abortion history was more in seropositive
      group (51.65 %) in comparison to the seronegative group (5.84 %) and the
      seropositive cattle were 8.84 times more likely to experience abortion than the
      seronegative cattle. The occurrence of abortion among different age groups varied
      significantly (p < 0.05). The findings revealed the presence of neosporosis in
      the southern peninsular India among cattle and water buffaloes and a strong
      association between the seroprevalence and abortion.

PMID- 22644734
TI  - A survey of Toxoplasma gondii antibodies by latex agglutination assay in dairy
      goats in Northern Tanzania.
AB  - Food-borne parasitic diseases, such as toxoplasmosis, are increasingly becoming a
      global food safety concern. A cross-sectional study was conducted to investigate
      seroprevalence and risk factors of Toxoplasma gondii seropositivity in apparently
      healthy, unvaccinated dairy goat flocks reared under mixed smallholders, northern
      Tanzania between April and October 2011. Flock- and animal-level data were
      collected using a questionnaire. Sera (n = 337) collected from goats aged >= 6
      months and from 102 flocks, respectively, were analyzed using modified Eiken
      latex agglutination test. A flock was classified as T. gondii seropositive if at
      least one animal tested positive. Titers considered diagnostically significant
      (>= 1:16) were detected in 19.3 % of goats and 45.17 % of flocks, respectively.
      The antibody levels ranged from 1:16 to 1:2,048 and among the seropositive goats,
      the proportion of high antibody levels (>= 1:2,048), suggestive of acute
      infection, was 1.5 %. The study revealed that goats raised in Babati are at a
      lower risk of acquiring T. gondii infection (P = 0.00209) than those which are
      raised in Arumeru district. The prevalence of T. gondii antibody was
      significantly higher in crossbred (24.7 %) and Saanen (24.4 %) breed goats than
      in local (14.3 %) and Toggenburg (12.1 %) and in females than in males (P =
      0.043). No significant difference was observed among goats kept under various
      husbandry practices. The relatively high seroprevalence detected in this study
      suggests that toxoplasmosis may be posing a significant animal and human health
      risk and that the consumption of goat meat may play a role in the transmission of
      the disease to humans.

PMID- 22644735
TI  - Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and
      radiation therapy leads to a therapeutic response in a murine model of prostate
      cancer.
AB  - Radiation therapy (RT) is an integral part of prostate cancer treatment across
      all stages and risk groups. Immunotherapy using a live, attenuated, Listeria
      monocytogenes-based vaccines have been shown previously to be highly efficient in
      stimulating anti-tumor responses to impact on the growth of established tumors in
      different tumor models. Here, we evaluated the combination of RT and
      immunotherapy using Listeria monocytogenes-based vaccine (ADXS31-142) in a mouse
      model of prostate cancer. Mice bearing PSA-expressing TPSA23 tumor were divided
      to 5 groups receiving no treatment, ADXS31-142, RT (10 Gy), control Listeria
      vector and combination of ADXS31-142 and RT. Tumor growth curve was generated by
      measuring the tumor volume biweekly. Tumor tissue, spleen, and sera were
      harvested from each group for IFN-gamma ELISpot, intracellular cytokine assay,
      tetramer analysis, and immunofluorescence staining. There was a significant tumor
      growth delay in mice that received combined ADXS31-142 and RT treatment as
      compared with mice of other cohorts and this combined treatment causes complete
      regression of their established tumors in 60 % of the mice. ELISpot and
      immunohistochemistry of CD8+ cytotoxic T Lymphocytes (CTL) showed a significant
      increase in IFN-gamma production in mice with combined treatment. Tetramer
      analysis showed a fourfold and a greater than 16-fold increase in PSA-specific
      CTLs in animals receiving ADXS31-142 alone and combination treatment,
      respectively. A similar increase in infiltration of CTLs was observed in the
      tumor tissues. Combination therapy with RT and Listeria PSA vaccine causes
      significant tumor regression by augmenting PSA-specific immune response and it
      could serve as a potential treatment regimen for prostate cancer.

PMID- 22644736
TI  - High throughput detection of tetracycline residues in milk using graphene or
      graphene oxide as MALDI-TOF MS matrix.
AB  - In this work, a new pre-analysis method for tetracyclines (TCs) detection from
      the milk samples was established. As a good accomplishment for the existing
      accurate quantification strategies for TCs detection, the new pre-analysis method
      was demonstrated to be simple, sensitive, fast, cost effective, and high
      throughput, which would do a great favor to the routine quality pre-analysis of
      TCs from milk samples. Graphene or graphene oxide was utilized, for the first
      time, as a duel-platform to enrich and detect the TCs by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). All
      together, four TCs were chosen as models: tetracycline, oxytetracycline,
      demeclocycline, and chlortetracycline. Due to the excellent electronic, thermal,
      and mechanical properties, graphene and graphene oxide were successfully applied
      as matrices for MALDI-TOF MS with free background inference in low mass range.
      Meanwhile, graphene or graphene oxide has a large surface area and strong
      interaction force with the analytes. By taking the advantage of these features,
      TCs were effectively enriched with the limit of detection (LOD) as low as 2 nM.

PMID- 22644737
TI  - A negative ion mass spectrometry approach to identify cross-linked peptides
      utilizing characteristic disulfide fragmentations.
AB  - Chemical cross-linking combined with mass spectrometry (MS) is an analytical tool
      used to elucidate the topologies of proteins and protein complexes. However,
      identification of the low abundance cross-linked peptides and modification sites
      amongst a large quantity of proteolytic fragments remains challenging. In this
      work, we present a strategy to identify cross-linked peptides by negative ion MS
      for the first time. This approach is based around the facile cleavages of
      disulfide bonds in the negative mode, and allows identification of cross-linked
      products based on their characteristic fragmentations. MS(3) analysis of the
      cross-linked peptides allows for their sequencing and identification, with
      residue specific location of cross-linking sites. We demonstrate the
      applicability of the commercially available cystine based cross-linking reagent
      dithiobis(succinimidyl) propionate (DSP) and identify cross-linked peptides from
      ubiquitin. In each instance, the characteristic fragmentation behavior of the
      cross-linked species is described. The data presented here indicate that this
      negative ion approach may be a useful tool to characterize the structures of
      proteins and protein complexes, and provides the basis for the development of
      high throughput negative ion MS chemical cross-linking strategies.

PMID- 22644738
TI  - Unidentified genetic variants influence pancreatic cancer risk: an analysis of
      polygenic susceptibility in the PanScan study.
AB  - Genome-wide association (GWA) studies have identified several pancreatic cancer
      (PanCa) susceptibility loci. Methods for assessment of polygenic susceptibility
      can be employed to detect the collective effect of additional association signals
      for PanCa. Using data on 492,651 autosomal single nucleotide polymorphisms (SNPs)
      from the PanScan GWA study (2,857 cases, 2,967 controls), we employed polygenic
      risk score (PRS) cross-validation (CV) methods to (a) confirm the existence of
      unidentified association signals, (b) assess the predictive value of PRSs, and
      (c) assess evidence for polygenic effects in specific genomic locations (genic
      vs. intergenic). After excluding SNPs in known PanCa susceptibility regions, we
      constructed PRS models using a training GWA dataset and then tested the model in
      an independent testing dataset using fourfold CV. We also employed a "power
      replication" approach, where power to detect SNP associations was calculated
      using a training dataset, and power was tested for association with "replication
      status" in a testing dataset. PRS scores constructed using >= 10% of genome-wide
      SNPs showed significant association with PanCa (P< 0.05) across the majority of
      CV analyses. Associations were stronger for PRSs restricted to genic SNPs
      compared to intergenic PRSs. The power-replications approach produced weaker
      associations that were not significant when restricting to SNPs with low pairwise
      linkage disequilibrium, whereas PRS results were robust to such restrictions.
      Although the PRS approach will not dramatically improve PanCa prediction, it
      provides strong evidence for unidentified association signals for PanCa. Our
      results suggest that focusing association studies on genic regions and conducting
      larger GWA studies can reveal additional PanCa susceptibility loci.

PMID- 22644739
TI  - Transmural pressure loading enhances gastric mucosal cell proliferation.
AB  - AIM: Although increased intraluminal pressure in the stomach due to gastric
      outlet obstruction or functional gastric motor dysfunction, including
      gastroparesis, may affect gastric mucosal integrity, the direct effect of
      mechanical pressure on gastric mucosal cells has not yet been fully investigated.
      The aims of this study were to determine whether exposure to transmural pressure
      would affect the proliferation of gastric mucosal cells and to elucidate the
      intracellular signaling pathways involved. METHODS: Cellular proliferation and
      DNA synthesis were evaluated in rat gastric epithelial cells exposed to high
      transmural pressures. The levels of activation of 3 MAP kinases, ERK, JNK, and
      p38, were assessed, and the induction of immediate early gene expression was
      examined. The activation of nuclear factor activator protein-1 (AP-1) was
      evaluated by an electrophoretic mobility shift assay. RESULTS: Exposure to high
      transmural pressure significantly increased DNA synthesis within 24 h, with the
      most marked increase observed after exposure to a pressure of 80 mmHg, and this
      increase was inhibited by the MEK1 inhibitor PD98059. Early activation of ERK
      kinase, but not of JNK or p38 kinase, was detected after pressure loading. Early
      induction of the c-fos and c-myc genes and activation of the AP-1 transcription
      factor were also demonstrated within 3 h of exposure to 80 mmHg of pressure.
      CONCLUSION: Gastric mucosal cell proliferation induced by exposure to high
      transmural pressure may be related to early activation of ERK, the induction of c
      fos and c-myc, and the activation of AP-1.

PMID- 22644742
TI  - Bin1: a new player in IBD barrier dysfunction.

PMID- 22644741
TI  - Quantitative estimates of motility from videocapsule endoscopy are useful to
      discern celiac patients from controls.
AB  - BACKGROUND: Prior work has shown that videocapsule endoscopy image features are a
      useful tool for quantitatively distinguishing the intestinal mucosal surface of
      untreated celiac patients from that of controls. The use of dynamic estimates of
      wall motility may further help to improve classification. METHODS: Videocapsule
      endoscopy clips (200 frames each, 2 frames/s, 576 * 576 pixels/frame) were
      acquired at five small intestinal locations in 11 untreated celiac patients
      (celiacs) and ten controls. Color images were converted to grayscale and analyzed
      frame-by-frame. Variations in the position and width of the center of the small
      intestinal lumen were quantitatively estimated. The darkest grayscale pixels were
      used as an estimate of the lumen center. Over 200 frames, the standard deviation
      of the lumen center xy position and the mean and standard deviation in lumen
      center width were used as dynamic estimates of wall motility. These parameters
      were plotted in three-dimensional space, and the best discriminant function was
      used to classify celiacs versus controls at each of the following five locations:
      (1) duodenal bulb, (2) distal duodenum, (3) jejunum, (4) ileum, and (5) distal
      ileum. RESULTS: The overall sensitivity for the classification of celiacs versus
      controls at all five locations was 98.2 %, while the specificity was 96.0 %. From
      location 1 to 5, there was a tendency for the lumen center width to diminish in
      terms of frame-to-frame variability by 7.6 % in celiacs (r (2) = 0.4) and 9.7 %
      in controls (r (2) = 0.7). CONCLUSIONS: In addition to examining the mucosal
      surface, videocapsule endoscopy can assess small bowel intestinal motility and
      aid in distinguishing celiac patients from controls.

PMID- 22644743
TI  - Gabapentin versus pregabalin in improving sleep quality and depression in
      hemodialysis patients with peripheral neuropathy: a randomized prospective
      crossover trial.
AB  - PURPOSE: In dialysis patients, painful peripheral neuropathy (PPN) is associated
      with sleep disturbance and mood disorders. Our goal was to compare the effects of
      gabapentin and pregabalin on improving sleep quality and depression among
      hemodialysis patients with PPN. METHODS: Fifty hemodialysis patients with PPN
      were randomized into 2 groups, to receive gabapentin and pregabalin,
      respectively. After 6 weeks of treatment, patients underwent a 2-week washout
      period, followed by crossover and another 6 weeks of treatment. All patients
      underwent electromyography (EMG) at the outset and completed the modified Short
      Form of McGill Pain Questionnaire (SF-MPQ), the Beck Depression Inventory (BDI)
      and the Pittsburgh Sleep Quality (PSQI) assessment at baseline and at the end of
      the study. Forty out of 50 patients completed the 14-week study period. RESULTS:
      Thirty-one out of 40 patients (77.5 %) had EMG-proven PPN. Both gabapentin and
      pregabalin significantly improved SF-MPQ, BDI and PSQI scores at the end of the
      study compared with pretreatment scores (p < 0.001). There was no significant
      difference between the two drugs in any studied parameter. CONCLUSIONS: Our
      results showed for the first time a good and similar efficacy of both drugs on
      pain intensity, quality of sleep and depression in hemodialysis patients with
      PPN.

PMID- 22644744
TI  - Ethnic differences in 25-hydroxyvitamin D levels and response to treatment in
      CKD.
AB  - AIM: Nutritional vitamin D [25(OH)D] deficiency is common in patients with
      chronic kidney disease (CKD). No studies have specifically examined the
      differences between ethnic groups in response to ergocalciferol ("D2") therapy.
      METHODS: A retrospective analysis was performed to evaluate the effectiveness of
      D2 therapy as recommended by the KDOQI guidelines in 184 Hispanic and Caucasian
      nondialysis CKD patients. RESULTS: Low 25(OH)D levels (<75 nmol/L) were found in
      89.4 % of Hispanics versus 61.4 % of Caucasians, despite similar degrees of CKD.
      Treatment per KDOQI guidelines resulted in 85.5 % of treated Hispanics and 66.7 %
      of treated Caucasians remaining vitamin D-deficient. Although both Hispanics and
      Caucasians had significant (P < 0.0001) changes in 25(OH)D levels, absolute
      changes were modest (12.5 +/- 2.0 nmol/mL in Hispanics, 20.0 +/- 3.5 nmol/L in
      Caucasians). The increase seen in Caucasians was significantly greater than in
      Hispanics (P < 0.0001). In multiple logistic regression modeling, Hispanic
      ethnicity remained independently associated with poorer response to therapy (P =
      0.0055), even after adjustment for other factors. CONCLUSIONS: While both
      Hispanics and Caucasians demonstrated suboptimal response to the KDOQI-guided
      vitamin D repletion strategy, Hispanic ethnicity was significantly associated
      with poorer response. Our findings may have implications for other darker-skinned
      populations, even in solar-rich environments.

PMID- 22644745
TI  - Neuropsychiatric complications of aging with HIV.
AB  - Persons over age 50 are not only aging with human immunodeficiency virus (HIV)
      infection but also represent a high proportion of new HIV infections.
      Neuropsychiatric symptoms, including depression, cognitive impairment, and
      substance abuse, are very common in individuals infected with HIV. However, there
      is little understanding of the relationship between these HIV-related comorbid
      conditions in newly infected elderly patients compared to uninfected elderly and
      those who have survived after 20 years of HIV/AIDS. We summarize the current
      theories and research that link aging and HIV with psychiatric illnesses and
      identify emerging areas for improved research, treatment, and patient care.

PMID- 22644746
TI  - Genotype imputation for African Americans using data from HapMap phase II versus
      1000 genomes projects.
AB  - Genotype imputation provides imputation of untyped single nucleotide
      polymorphisms (SNPs) that are present on a reference panel such as those from the
      HapMap Project. It is popular for increasing statistical power and comparing
      results across studies using different platforms. Imputation for African American
      populations is challenging because their linkage disequilibrium blocks are
      shorter and also because no ideal reference panel is available due to admixture.
      In this paper, we evaluated three imputation strategies for African Americans.
      The intersection strategy used a combined panel consisting of SNPs polymorphic in
      both CEU and YRI. The union strategy used a panel consisting of SNPs polymorphic
      in either CEU or YRI. The merge strategy merged results from two separate
      imputations, one using CEU and the other using YRI. Because recent investigators
      are increasingly using the data from the 1000 Genomes (1KG) Project for genotype
      imputation, we evaluated both 1KG-based imputations and HapMap-based imputations.
      We used 23,707 SNPs from chromosomes 21 and 22 on Affymetrix SNP Array 6.0
      genotyped for 1,075 HyperGEN African Americans. We found that 1KG-based
      imputations provided a substantially larger number of variants than HapMap-based
      imputations, about three times as many common variants and eight times as many
      rare and low-frequency variants. This higher yield is expected because the 1KG
      panel includes more SNPs. Accuracy rates using 1KG data were slightly lower than
      those using HapMap data before filtering, but slightly higher after filtering.
      The union strategy provided the highest imputation yield with next highest
      accuracy. The intersection strategy provided the lowest imputation yield but the
      highest accuracy. The merge strategy provided the lowest imputation accuracy. We
      observed that SNPs polymorphic only in CEU had much lower accuracy, reducing the
      accuracy of the union strategy. Our findings suggest that 1KG-based imputations
      can facilitate discovery of significant associations for SNPs across the whole
      MAF spectrum. Because the 1KG Project is still under way, we expect that later
      versions will provide better imputation performance.

PMID- 22644747
TI  - Basic apoptotic and necrotic cell death in human liver carcinoma (HepG2 ) cells
      induced by synthetic azamacrocycle.
AB  - Treatment of diseases with synthetic materials has been an aspiration of mankind
      since the dawn of human development. In this research, three complex compounds of
      azamacrocycle (TD1, TD2, and TD3) were synthesized, and experiments were
      conducted to determine whether their toxicity to human liver carcinoma (HepG2 )
      cells is associated with apoptotic and/or necrotic cell death. Cell survival was
      determined by MTT assay. Apoptosis and necrosis were measured by annexin V
      FITC/PI assay using the flow cytometry and by propidium iodide (PI) assay using
      the cellometer vision. HepG2 cells were treated with different concentrations of
      azamacrocycles for 48 h. Results from MTT assay indicated that all the three
      azamacrocycles significantly (p < 0.05) reduce cell viability in a dose-dependent
      manner, showing 48 h-LD50 values of about 37.97, 33.60, and 19.29 MUM, for TD3,
      TD1 and TD2, respectively. Among the three compounds tested, TD2 showed the most
      pronounced cytotoxic activity against HepG2 cells, being about twofold more
      potent than TD3. The order of toxicity was TD2 > TD1 > TD3. Because TD2 exerted
      the most cytotoxic activity against HepG2 cells, it was used in the subsequent
      apoptosis and necrosis-related experiments. The flow cytometry assessment showed
      a strong dose-response relationship with regard to TD2 exposure and annexin V/PI
      positive cells. PI assay data indicated that TD2 exposure increased the
      proportion of fluorescence positive cells. Overall, our results indicate that
      azamacrocycle toxicity to HepG2 cells is associated with apoptotic and necrotic
      cell death resulting from phosphatidylserine externalization and loss of membrane
      integrity.

PMID- 22644759
TI  - Trait anxiety and the neural efficiency of manipulation in working memory.
AB  - The present study investigates the effects of trait anxiety on the neural
      efficiency of working memory component functions (manipulation vs. maintenance)
      in the absence of threat-related stimuli. For the manipulation of affectively
      neutral verbal information held in working memory, high- and low-anxious
      individuals (N = 46) did not differ in their behavioral performance, yet trait
      anxiety was positively related to the neural effort expended on task processing,
      as measured by BOLD signal changes in fMRI. Higher levels of anxiety were
      associated with stronger activation in two regions implicated in the goal
      directed control of attention--that is, right dorsolateral prefrontal cortex
      (DLPFC) and left inferior frontal sulcus--and with stronger deactivation in a
      region assigned to the brain's default-mode network--that is, rostral-ventral
      anterior cingulate cortex. Furthermore, anxiety was associated with a stronger
      functional coupling of right DLPFC with ventrolateral prefrontal cortex. We
      interpret our findings as reflecting reduced processing efficiency in high
      anxious individuals and point out the need to consider measures of functional
      integration in addition to measures of regional activation strength when
      investigating individual differences in neural efficiency. With respect to the
      functions of working memory, we conclude that anxiety specifically impairs the
      processing efficiency of (control-demanding) manipulation processes (as opposed
      to mere maintenance). Notably, this study contributes to an accumulating body of
      evidence showing that anxiety also affects cognitive processing in the absence of
      threat-related stimuli.

PMID- 22644760
TI  - A glass full of optimism: enrichment effects on cognitive bias in a rat model of
      depression.
AB  - Investigations of cognitive biases in animals are conceptually and
      translationally valuable because they contribute to animal welfare research and
      help to extend and refine our understanding of human emotional disorders, where
      biased information processing is a critical causal and maintenance factor. We
      employed the "learned helplessness" genetic rat model of depression in studying
      cognitive bias and its modification by environmental manipulations. Using a
      spatial judgment task, responses to ambiguous spatial cues were assessed before
      and after environmental enrichment to test whether this manipulation would cause
      an optimistic shift in emotional state. Twenty-four congenitally helpless and
      nonhelpless male rats were trained to discriminate two different locations,
      "rewarded" versus "aversive." After successful acquisition of this spatial
      discrimination, cognitive bias was probed by measuring responses to three
      ambiguous locations. Latencies to "reach" and to actively "choose" a goal pot
      were recorded alongside exploratory behaviors. An overall strain difference was
      observed, with helpless rats displaying longer "reach" latencies than nonhelpless
      rats. This implies a "pessimistic" response bias in helpless rats, underscoring
      their depressive-like phenotype. No strain differences were observed regarding
      other behavioral measures. Half of the animals were then transferred to enriched
      cages and retested. Environmental enrichment resulted in reduced "choose"
      latencies in both rat strains, associating enrichment with more optimistic
      interpretations of ambiguous cues. Our results emphasize the suitability of
      cognitive bias measurement for animal emotion assessment. They extend the
      methodological repertoire for characterizing complex phenotypes and bear
      implications for animal welfare research and for the use of animal models in
      preclinical research.

PMID- 22644762
TI  - Sequence analysis of the NSP2, ORF5, and ORF7 genes of 11 PRRS virus isolates
      from China.
AB  - During a tracing investigation of blue ear disease in China conducted from
      January to November 2008, 11 porcine reproductive and respiratory syndrome virus
      (PRRSV) isolates were collected from eight provinces including Liaoning, Jilin,
      Hebei, Shandong, Henan, Shanghai, Zhejiang, and Guangxi. The complete gene
      sequences of the NSP2, ORF5, and ORF7 genes from these 11 PRRSV isolates were
      amplified, cloned and detected by RT-PCR and then compared with the published
      sequences of other strains. The results showed that all of the isolates
      genotypically belonged to an American strain, but shared high homology with JXA1,
      the highly pathogenic strain endemic to China. All of the 11 PRRSV isolates
      demonstrated a 90-nucleotide deletion in the NSP2 gene, suggesting that the main
      epidemic of PRRSV in 2008 was due to this gene deletion isolate. More consistent
      mutations were found in specific regions of the ORF5 and ORF7 genes of the 11
      PRRSV isolates, such as the signal peptide and transmembrane regions of GP5 and
      the Pat 7 motif of the N protein. Whether these mutations influence nuclear
      localization of PRRSV requires confirmation by future studies.

PMID- 22644763
TI  - Cotton leaf curl Multan betasatellite strains cloned from Gossypium barbadense
      further supports selection due to host resistance.
AB  - The cotton leaf curl Multan betasatellite encodes an essential pathogenicity
      determinant involved in induction of disease symptoms. We have shown recently
      that a recombinant betasatellite with a satellite conserved region derived from
      the tomato leaf curl betasatellite, is prevalent in the Punjab province and is
      associated with the breakdown of resistance in cotton to cotton leaf curl
      disease. We intended to see if the betasatellite that was associated with the
      first epidemic is still being maintained in some other hosts. We cloned
      betasatellite from G. barbadense, a cotton species highly susceptible to the
      disease. We found that both the original and recombinant betasatellite are
      associated with this cotton species. These findings strengthen our hypothesis
      that the recombinant betasatellite now prevalent on commercial cotton has been
      selected due to its ability to cross the host resistance barrier.

PMID- 22644764
TI  - Troop size and human-modified habitat affect the ranging patterns of a chacma
      baboon population in the cape peninsula, South Africa.
AB  - Differences in group size and habitat use are frequently used to explain the
      extensive variability in ranging patterns found across the primate order.
      However, with few exceptions, our understanding of primate ranging patterns stems
      from studies of single groups and both intra- and inter-specific meta-analyses.
      Studies with many groups and those that incorporate whole populations are rare
      but important for testing socioecological theory in primates. We quantify the
      ranging patterns of nine chacma baboon troops in a single population and use
      Spearman rank correlations and generalized linear mixed models to analyze the
      effects of troop size and human-modified habitat (a proxy for good quality
      habitat) on home range size, density (individuals/km(2) ), and daily path length.
      Intrapopulation variation in home range sizes (1.5-37.7 km(2) ), densities (1.3
      12.1 baboons/km(2) ), and daily path lengths (1.80-6.61 km) was so vast that
      values were comparable to those of baboons inhabiting the climatic extremes of
      their current distribution. Both troop size and human-modified habitat had an
      effect on ranging patterns. Larger troops had larger home ranges and longer daily
      path lengths, while troops that spent more time in human-modified habitat had
      shorter daily path lengths. We found no effect of human-modified habitat on home
      range size or density. These results held when we controlled for the effects of
      both a single large outlier troop living exclusively in human-modified habitat
      and baboon monitors on our spatial variables. Our findings confirm the ability of
      baboons, as behaviorally adaptable dietary generalists, to not only survive but
      also to thrive in human-modified habitats with adjustments to their ranging
      patterns in accordance with current theory. Our findings also caution that
      studies focused on only a small sample of groups within a population of adaptable
      and generalist primate species may underestimate the variability in their
      respective localities.

PMID- 22644765
TI  - Overexpression of phytochrome A and its hyperactive mutant improves shade
      tolerance and turf quality in creeping bentgrass and zoysiagrass.
AB  - Phytochrome A (phyA) in higher plants is known to function as a far-red/shade
      light-sensing photoreceptor in suppressing shade avoidance responses (SARs) to
      shade stress. In this paper, the Avena PHYA gene was introduced into creeping
      bentgrass (Agrostis stolonifera L.) and zoysiagrass (Zoysia japonica Steud.) to
      improve turf quality by suppressing the SARs. In addition to wild-type PHYA, a
      hyperactive mutant gene (S599A-PHYA), in which a phosphorylation site involved in
      light-signal attenuation was removed, was also transformed into the turfgrasses.
      Phenotypic traits of the transgenic plants were compared to assess the
      suppression of SARs under a simulated shade condition and outdoor field
      conditions after three growth seasons. Under the shade condition, the S599A-PhyA
      transgenic creeping bentgrass plants showed shade avoidance-suppressing
      phenotypes with a 45 % shorter leaf lengths, 24 % shorter internode lengths, and
      twofold increases in chlorophyll concentrations when compared with control
      plants. Transgenic zoysiagrass plants overexpressing S599A-PHYA also showed shade
      tolerant phenotypes under the shade condition with reductions in leaf length (15
      %), internode length (30 %), leaf length/width ratio (19 %) and leaf area (22 %),
      as well as increases in chlorophyll contents (19 %) and runner lengths (30 %)
      compared to control plants. The phenotypes of transgenic zoysiagrass were also
      investigated in dense field habitats, and the transgenic turfgrass exhibited
      shade-tolerant phenotypes similar to those observed under laboratory shade
      conditions. Therefore, the present study suggests that the hyperactive phyA is
      effective for the development of shade-tolerant plants, and that the shade
      tolerance nature is sustained under field conditions.

PMID- 22644766
TI  - Xylem defense wood of Norway spruce compromised by the pathogenic white-rot
      fungus Heterobasidion parviporum shows a prolonged period of selective decay.
AB  - Heterobasidion parviporum, a common pathogenic white-rot fungus in managed Norway
      spruce forests in northern and central Europe, causes extensive decay columns
      within stem heartwood of the host tree. Infected trees combat the lateral spread
      of decay by bordering the heartwood with a fungistatic reaction zone
      characterized by elevated pH and phenol content. To examine the mode of fungal
      feeding in the reaction zone of mature Norway spruce trees naturally infected by
      H. parviporum, we conducted spatial profiling of pectin and hemicellulose
      composition, and established transcript levels of candidate fungal genes encoding
      enzymes involved in degradation of the different cell wall components of wood.
      Colonized inner heartwood showed pectin and hemicellulose concentrations similar
      to those of healthy heartwood, whereas the carbohydrate profiles of compromised
      reaction zone, irrespective of the age of fungal activity in the tissue,
      indicated selective fungal utilization of galacturonic acid, arabinose, xylose
      and mannose. These data show that the rate of wood decay in the reaction zone is
      slow. While the up-regulation of genes encoding pectinases and hemicellulases
      preceded that of the endoglucanase gene during an early phase of fungal
      interaction with xylem defense, the manganese peroxidase gene showed similar
      transcript levels during different phases of wood colonization. It seems
      plausible that the reaction zone components of Norway spruce interfere with both
      lignin degradation and the associated co-hydrolysis of hemicelluloses and pectin,
      resulting in a prolonged phase of selective decay.

PMID- 22644767
TI  - Characterization of the regulatory network of BoMYB2 in controlling anthocyanin
      biosynthesis in purple cauliflower.
AB  - Purple cauliflower (Brassica oleracea L. var. botrytis) Graffiti represents a
      unique mutant in conferring ectopic anthocyanin biosynthesis, which is caused by
      the tissue-specific activation of BoMYB2, an ortholog of Arabidopsis PAP2 or
      MYB113. To gain a better understanding of the regulatory network of anthocyanin
      biosynthesis, we investigated the interaction among cauliflower MYB-bHLH-WD40
      network proteins and examined the interplay of BoMYB2 with various bHLH
      transcription factors in planta. Yeast two-hybrid studies revealed that
      cauliflower BoMYBs along with the other regulators formed the MYB-bHLH-WD40
      complexes and BobHLH1 acted as a bridge between BoMYB and BoWD40-1 proteins.
      Different BoMYBs exhibited different binding activity to BobHLH1. Examination of
      the BoMYB2 transgenic lines in Arabidopsis bHLH mutant backgrounds demonstrated
      that TT8, EGL3, and GL3 were all involved in the BoMYB2-mediated anthocyanin
      biosynthesis. Expression of BoMYB2 in Arabidopsis caused up-regulation of AtTT8
      and AtEGL3 as well as a subset of anthocyanin structural genes encoding flavonoid
      3'-hydroxylase, dihydroflavonol 4-reductase, and leucoanthocyanidin dioxygenase.
      Taken together, our results show that MYB-bHLH-WD40 network transcription factors
      regulated the bHLH gene expression, which may represent a critical feature in the
      control of anthocyanin biosynthesis. BoMYB2 together with various BobHLHs
      specifically regulated the late anthocyanin biosynthetic pathway genes for
      anthocyanin biosynthesis. Our findings provide additional information for the
      complicated regulatory network of anthocyanin biosynthesis and the
      transcriptional regulation of transcription factors in vegetable crops.

PMID- 22644769
TI  - Letter from the guest editor.

PMID- 22644768
TI  - Molecular cloning and characterization of OsCHR4, a rice chromatin-remodeling
      factor required for early chloroplast development in adaxial mesophyll.
AB  - Mi-2 protein, the central component of the NuRD nucleosome remodeling and histone
      deacetylase complex, plays a role in transcriptional repression in animals. Mi-2
      like genes have been reported in Arabidopsis, though their function in monocots
      remains largely unknown. In the present study, a rice Mi-2-like gene, OsCHR4
      (Oryza sativa Chromatin Remodeling 4, LOC_Os07g03450), was cloned from a rice
      mutant with adaxial albino leaves. The Oschr4 mutant exhibited defective
      chloroplasts in adaxial mesophyll, but not in abaxial mesophyll. Ultrastructural
      observations indicated that proplastid growth and/or thylakoid membrane formation
      in adaxial mesophyll cells was blocked in the Oschr4 mutant. Subcellular
      localization revealed that OsCHR4::GFP fusion protein was targeted to the nuclei.
      OsCHR4 was mainly expressed in the root meristem, flower, vascular bundle, and
      mesophyll cells by promoter::GUS analysis in transgenic rice. The transcripts of
      some nuclear- and plastid-encoded genes required for early chloroplast
      development and photosynthesis were decreased in the adaxial albino mesophyll of
      the Oschr4 mutant. These observations provide evidence that OsCHR4, the rice Mi-2
      like protein, plays an important role in early chloroplast development in adaxial
      mesophyll cells. The results increase our understanding of the molecular
      mechanism underlying tissue-specific chloroplast development in plants.

PMID- 22644770
TI  - Psoriasis and its comorbidities.
AB  - Psoriasis is a multi-systemic chronic inflammatory skin disease targeting 2% to
      3% of the general population. It is a prototype of immune dysregulation mediated
      by TH1 proinflammatory cytokines such as TNF-?, IFN-Y, IL-6, and IL-12, to name a
      few. Psoriasis, traditionally viewed as an inflammatory skin disorder of unknown
      origin, is increasingly recognized as an inflammatory skin disease with far
      reaching systemic effects. There is growing and emerging evidence that psoriasis
      patients have a higher prevalence of associated comorbid disease with
      cardiometabolic dysfunction and psoriatic arthritis being at the forefront. It
      appears that psoriatic skin disease severity portends a serious risk for
      development of these comorbidities. As such, patients with moderate to severe
      psoriatic skin disease are found to have a higher association with these
      extracutaneous disease manifestations.

PMID- 22644771
TI  - Considerations when initiating psoriasis patients on biologic therapy.
AB  - Several types of systemic therapies exist to treat psoriasis. These include
      traditional immunosuppressive agents such as cyclosporine and methotrexate. Oral
      retinoids such as acitretin may also be appropriate in some patients. The scope
      of this paper, however, will focus on the use of targeted immunologic therapies,
      know as biologic agents.

PMID- 22644772
TI  - A prospective open-label clinical trial of efficacy of the every week
      administration of adalimumab in the treatment of hidradenitis suppurativa.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating disease refractory to
      treatment. As its impact on patients' quality of life is strong, it requires
      effective treatment. OBJECTIVES: To evaluate the efficacy and safety of
      adalimumab using a higher dosage regimen for HS treatment and establish the
      recurrence-free interval after treatment discontinuation. MATERIAL AND METHODS:
      Patients with moderate to severe HS were treated with 80 mg adalimumab at
      baseline, followed by 40 mg every week for 24 weeks. Subsequently, patients
      entered an observational period for another 24 weeks. Clinical evaluation took
      place every 4 weeks during the study period. Sartorius scoring system was used as
      assessment tool regarding disease activity. At the same time points patients
      evaluated disease activity by Visual Analogue Scale (VAS). They completed a
      Dermatology Life Quality Index (DLQI) questionnaire at baseline and at weeks 24
      and 48. RESULTS: Fifteen patients completed the study. Significant reduction in
      Sartorius score was obtained by week 24 with a marked improvement during the
      first month. Mean time to relapse was 11 weeks after treatment cessation, but
      even at the final visit Sartorius score was significantly lower than at baseline.
      VAS score and DLQI showed a significant decrease at week 24. There was
      significant worsening at week 48, however both scores remained significantly
      lower than baseline levels. CONCLUSIONS: Our study data demonstrate the
      significant efficacy of the once weekly regimen, as well as its benefit regarding
      time to recurrence. However, the question if benefit outweighs the risk of a long
      term anti-TNF-alpha antagonist's administration needs still to be answered.

PMID- 22644773
TI  - Quality of life of nursing-home residents with dementia subject to surveillance
      technology versus physical restraints: an explorative study.
AB  - OBJECTIVE: As physical restraints should only be used in exceptional cases, there
      is an urgent need for alternatives to restraint use. Surveillance technology
      could be such an alternative. This study explored whether nursing-home residents
      with dementia subjected to surveillance technology had better quality of life
      scores for mood, behavioral and societal dimensions than residents with physical
      restraints. METHODS: Quality of life was assessed longitudinally, with three
      measurements in six psychogeriatric nursing homes of residents with surveillance
      technology (n = 170) and residents with physical restraints (n = 22). QUALIDEM
      subscales were used to measure five dimensions of quality of life. Multilevel
      longitudinal univariate and multivariate regression techniques were used to
      analyze the data. RESULTS: Because physical restraints were almost exclusively
      used in residents with low activities of daily living (ADL) independency (18 of
      the 22), we restricted the regression analyses to residents with a Barthel Index
      score <= 5 (overall n = 53). Univariate results showed that highly ADL-dependent
      residents with surveillance technology had significantly more positive affect
      than highly ADL-dependent residents with physical restraints. However, this
      difference proved to be no longer significant after adjustment for the
      confounders: age, sex and stage of dementia. CONCLUSIONS: Quality of life of
      highly ADL-dependent nursing-home residents with dementia seems to be unrelated
      to the use of surveillance technology as opposed to physical restraints.

PMID- 22644774
TI  - The "pure-study" learning curve: the learning curve without cumulative testing.
AB  - The customary assumption in the study of human learning using alternating study
      and test trials is that learning occurs during study trials and that test trials
      are useful only to measure learning. In fact, tests seem to play little role in
      the development of learning, because the learning curve is similar even when the
      number of test trials varies widely (Tulving, Journal of verbal learning and
      verbal behavior 6:175-184, 1967). However, this outcome seems odd, because other
      research has shown that testing fosters greater long-term learning than does
      studying. We report three experiments addressing whether tests affect the shape
      of the learning curve. In two of the experiments, we examined this issue by
      varying the number of spaced study trials in a sequence and examining performance
      on only a single test trial at the end of the series (a "pure-study" learning
      curve). We compared these pure-study learning curves to standard learning curves
      and found that the standard curves increase more rapidly and reach a higher level
      in both free recall (exp. 1) and paired-associate learning (exp. 2). In
      Experiment 3, we provided additional study trials in the "pure-study" condition
      to determine whether the standard (study-test) condition would prove superior to
      a study-study condition. The standard condition still produced better retention
      on both immediate and delayed tests. Our experiments show that test trials play
      an important role in the development of learning using both free-recall (exps. 1
      and 3) and paired-associate (exp. 2) procedures. Theories of learning have
      emphasized processes that occur during study, but our results show that processes
      engaged during tests are also critical.

PMID- 22644775
TI  - Distinct functions of JNK and c-Jun in oxidant-induced hepatocyte death.
AB  - Overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling is a central
      mechanism of hepatocyte injury and death including that from oxidative stress.
      However, the functions of JNK and c-Jun are still unclear, and this pathway also
      inhibits hepatocyte death. Previous studies of menadione-induced oxidant stress
      demonstrated that toxicity resulted from sustained JNK/c-Jun activation as death
      was blocked by the c-Jun dominant negative TAM67. To further delineate the
      function of JNK/c-Jun signaling in hepatocyte injury from oxidant stress, the
      effects of direct JNK inhibition on menadione-induced death were examined. In
      contrast to the inhibitory effect of TAM67, pharmacological JNK inhibition by
      SP600125 sensitized the rat hepatocyte cell line RALA255-10G to death from
      menadione. SP600125 similarly sensitized mouse primary hepatocytes to menadione
      toxicity. Death from SP600125/menadione was c-Jun dependent as it was blocked by
      TAM67, but independent of c-Jun phosphorylation. Death occurred by apoptosis and
      necrosis and activation of the mitochondrial death pathway. Short hairpin RNA
      knockdowns of total JNK or JNK2 sensitized to death from menadione, whereas a
      jnk1 knockdown was protective. Jnk2 null mouse primary hepatocytes were also
      sensitized to menadione death. JNK inhibition magnified decreases in cellular ATP
      content and beta-oxidation induced by menadione. This effect mediated cell death
      as chemical inhibition of beta-oxidation also sensitized cells to death from
      menadione, and supplementation with the beta-oxidation substrate oleate blocked
      death. Components of the JNK/c-Jun signaling pathway have opposing functions in
      hepatocyte oxidant stress with JNK2 mediating resistance to cell death and c-Jun
      promoting death.

PMID- 22644776
TI  - Prognostic value of cetuximab-related skin toxicity in metastatic colorectal
      cancer patients and its correlation with parameters of the epidermal growth
      factor receptor signal transduction pathway: results from a randomized trial of
      the GERMAN AIO CRC Study Group.
AB  - Skin toxicity is a frequent adverse event of epidermal growth factor receptor
      (EGFR) targeting agents. Occurrence of cetuximab-induced skin toxicity (Cet-ST)
      correlates with better treatment response and longer survival times. Molecular
      markers predicting Cet-ST are still missing. This investigation analyzed the
      value of Cet-ST for treatment efficacy in a randomized trial comparing cetuximab
      plus capecitabine/irinotecan to cetuximab plus capecitabine/oxaliplatin as first
      line treatment of metastatic colorectal cancer. Patient characteristics and
      molecular parameters (KRAS mutation, EGFR-FISH, EGFR-IHC and EGFR intron-1
      polymorphism) of the tumour were correlated with response and Cet-ST. Cet-ST
      grade 0-1 was observed in 31%, grade 2-3 in 69% of patients. Outcome favoured
      patients with grade 2-3 Cet-ST with regard to overall response rate (62 vs. 41%),
      PFS (7.8 vs. 5.2 months) and overall survival (OS) (30.3 vs. 18.0 months). First
      cycle rash was observed in 66% of patients and corresponded with longer survival
      (30.7 vs. 20.2 months, p = 0.007). Patients without Cet-ST had a poor outcome
      (PFS, 1.9 months; OS, 11 months). The correlation of Cet-ST with survival was
      specifically evident in patients with KRAS codon-12-mutated tumours assumed to be
      cetuximab resistant. In multivariate analysis of patient characteristics, male
      gender and younger age were significantly correlated with Cet-ST. Among molecular
      parameters, no significant correlation with Cet-ST was found. Cet-ST is an early
      predictor of treatment efficacy in cetuximab-treated patients. This effect of Cet
      ST is independent of the KRAS mutation status, suggesting that Cet-ST rather
      relates to constitutional factors of the patient than alterations of the EGFR
      pathway in the tumour.

PMID- 22644777
TI  - The effects of childhood SNAP use and neighborhood conditions on adult body mass
      index.
AB  - The disproportionate number of individuals who are obese or overweight in the low
      income U.S. population has raised interest in the influence of neighborhood
      conditions and public assistance programs on weight and health. Generally,
      neighborhood effects and program participation effects have been explored in
      separate studies. We unite these two areas of inquiry, using the 1968-2005 Panel
      Study of Income Dynamics (PSID) to examine the long-term effects of childhood
      Supplemental Nutrition Assistance Program (SNAP) participation, neighborhood
      conditions, and the interaction of these two, on adult body mass index (BMI).
      Using sibling fixed-effects models to account for selection bias, we find that
      relative to children in other low-income families, children in SNAP-recipient
      households have higher average adult BMI values. However, the effects of
      childhood SNAP usage are sensitive to both residential neighborhood and age at
      receipt. For those growing up in advantaged neighborhoods, projected adult BMI is
      higher for children in SNAP-recipient households than for children in low-income,
      nonrecipient households. In contrast, for those growing up in less-advantaged
      areas, adult BMI differences between children in SNAP-recipient and those in low
      income, nonrecipient households are small. SNAP usage during preschool years (0
      to 4) has no impact on adult BMI scores. However, at later childhood ages, the
      time elapsed receiving SNAP income increases adult BMI values relative to a
      condition of low-income nonreceipt.

PMID- 22644778
TI  - Maternal Smad3 deficiency compromises decidualization in mice.
AB  - Transforming growth factor (TGF)-beta and activin, members of TGF-beta
      superfamily, are abundantly expressed in the endometrium and regulate
      decidualization of endometrial stroma. Smad2 and Smad3 are receptor-regulated
      Smads (R-Smads) that transduce extracellular TGF-beta/activin/Nodal signaling. In
      situ hybridization results showed that Smad3 was highly expressed in the decidual
      zone during the peri-implantation period in mice. By using artificial
      decidualization, we found that Smad3 null mice showed partially compromised
      decidualization. We therefore hypothesized that Smad2 might compensate for the
      function of Smad3 during the process of decidualization. Smad2 was also highly
      expressed in the decidual zone and phosphorylated Smad2 was much more abundantly
      increased in the deciduoma of Smad3 null mice than for wild-type (WT) mice. We
      further employed an in vitro uterine stromal cell decidualization model, and
      found that decidual prolactin-related protein (dPRP) and cyclin D3, which are
      well-known markers for decidual cells, were significantly down-regulated in Smad3
      null decidual cells, and were much more significantly reduced when the expression
      of Smad2 was simultaneously silenced by its siRNA (P < 0.05). However, the
      expression levels of dPRP and cyclin D3 remained the same when Smad2 was silenced
      in WT decidual cells. Collectively, these findings provide evidence for an
      important role of Smad3 in decidualization and suggest that Smad2 and Smad3 may
      have redundant roles in decidualization.

PMID- 22644779
TI  - Anatomical landmarks for transoral robotic tongue base surgery: comparison
      between endoscopic, external and radiological perspectives.
AB  - PURPOSE: To describe the transoral viewpoint of the tongue base anatomy, focusing
      on a superior to inferior perspective, which is less familiar to the head and
      neck surgeon but, at the same time, worthy to be known given the expanding
      interest and diffusion of the transoral robotic technique. METHODS: Seven heads
      were dissected, two with the Da Vinci((r)) robotic system, three by means of a
      transoral endoscopic approach and another two by means of a lateral "traditional"
      external approach. Ten normal patients, with normal oral cavity and oropharynx,
      were studied as control samples by means of a 3-T MRI scanner. RESULTS: Major
      neurovascular elements are placed laterally and deeply within the tongue base.
      Dissection within intrinsic and genioglossus muscles is safe because the main
      trunk of the lingual artery lies on the lateral surface of genioglossus muscle,
      covered by the hyoglossus muscle. The hypoglossal nerve, with its comitant vein,
      is more lateral, lying on the external surface of the hyoglossus muscle.
      Radiological evaluation can visualize important details of this complex anatomy.
      The position of the vessels can be directly identified, whereas major nerves are
      more difficult to be visualized unless they are surrounded by fibro-fatty tissue.
      CONCLUSIONS: A medial to lateral dissection of the tongue base can be considered
      safe. A strict collaboration with the radiologist is helpful in approaching these
      cases by means of a robotic technique and in improving a true 3D understanding of
      this complex anatomy.

PMID- 22644780
TI  - Recent advances in medical imaging: anatomical and clinical applications.
AB  - The aim of this paper was to present an overview of the most important recent
      advances in medical imaging and their potential clinical and anatomical
      applications. Dramatic changes have been particularly observed in the field of
      computed tomography (CT) and magnetic resonance imaging (MRI). Computed
      tomography (CT) has been completely overturned by the successive development of
      helical acquisition, multidetector and large area-detector acquisition.
      Visualising brain function has become a new challenge for MRI, which is called
      functional MRI, currently based principally on blood oxygenation level-dependent
      sequences, which could be completed or replaced by other techniques such as
      diffusion MRI (DWI). Based on molecular diffusion due to the thermal energy of
      free water, DWI offers a spectrum of anatomical and clinical applications,
      ranging from brain ischemia to visualisation of large fibrous structures of the
      human body such as the anatomical bundles of white matter with diffusion tensor
      imaging and tractography. In the field of X-ray projection imaging, a new low
      dose device called EOS has been developed through new highly sensitive detectors
      of X-rays, allowing for acquiring frontal and lateral images simultaneously.
      Other improvements have been briefly mentioned. Technical principles have been
      considered in order to understand what is most useful in clinical practice as
      well as in the field of anatomical applications. Nuclear medicine has not been
      included.

PMID- 22644781
TI  - Phosphorylation of signal transducer and activator of transcription 3 in soft
      tissue leiomyosarcoma is associated with a better prognosis.
AB  - Signal transducer and activator of transcription (STAT) 3 mediates a broad range
      of biological processes, including cell survival and proliferation, and STAT3 has
      generally been regarded as a pro-oncogenic transcription factor. We investigated
      the phosphorylation status of STAT3 and the protein expression of the suppressor
      of cytokine signaling 3 (SOCS3) by immunohistochemistry in 145 formalin-fixed,
      paraffin-embedded samples of soft tissue leiomyosarcoma (LMS), including 129
      primary tumors. Eight benign soft tissue smooth muscle tumors were also examined.
      Thirteen frozen LMS samples, which were paired with normal tissue samples, were
      assessed by Western blot analysis for the phosphorylation of STAT3 and SOCS3
      expression. Immunohistochemical study showed that the phosphorylation of STAT3
      was not a major event in LMS (37%). Moreover, phosphorylated STAT3 (pSTAT3)
      expression was significantly correlated with a better prognosis. Overexpression
      of SOCS3 was recognized in 52% of the cases and negatively correlated with pSTAT3
      expression. Among the benign tumors, 63 and 25% were positive for pSTAT3 and
      SOCS3, respectively. Immunoblotting detected pSTAT3 in all tumor samples, but at
      lower levels than in non-neoplastic tissue. SOCS3 was detected in 92% (12 out of
      13) of tumor tissues, but in none of the normal tissues. Contrary to the previous
      investigations of many other malignant tumors, STAT3 was inactivated in most LMS
      cases, likely owing to SOCS3 overexpression. STAT3 might not contribute to the
      progression of soft tissue LMS, and the phosphorylation status of STAT3 has the
      potential to be a favorable prognostic marker of LMS.

PMID- 22644782
TI  - Morphological changes of the epineurium in leprosy: a new finding detected by
      high-resolution sonography.
AB  - INTRODUCTION: From histopathological studies of peripheral nerves in leprosy, it
      is known that the epineurium can be thickened. We measured the epineurial
      thickness of the ulnar nerve by high resolution sonography (HRUS). METHODS: The
      epineurium of the ulnar nerve was measured above the elbow on transverse scan in
      25 healthy controls and 26 leprosy patients. RESULTS: The mean epineurial
      thickness was 0.77 mm (95% confidence interval [CI] 0.66-0.88) in symptomatic
      ulnar nerves (n = 20), 0.58 mm (CI 0.51-0.65) in asymptomatic nerves (n = 30),
      and 0.49 mm (CI 0.44-0.54) in healthy controls (n = 25) (P = 0.0001). This
      thickening was related to the cross-sectional area of the ulnar nerve, but not
      with increased blood flow. CONCLUSIONS: The epineurium of the ulnar nerve can be
      measured with the use of HRUS, and it is often strikingly thickened in leprosy
      patients, especially in those with ulnar involvement.

PMID- 22644783
TI  - Mitochondrial alteration in malignantly transformed human small airway epithelial
      cells induced by alpha-particles.
AB  - Human small airway epithelial cells (SAECs) immortalized with human telomerase
      reverse transcriptase were exposed to either a single or multiple doses of alpha
      particles. Irradiated cells showed a dose-dependent cytotoxicity and progressive
      neoplastic transformation phenotype. These included an increase in saturation
      density of growth, a greater resistance to N-phosphonoacetyl-L-aspartate, faster
      anchorage-independent growth, reinforced cell invasion and c-Myc expression. In
      addition, the transformed cells formed progressively growing tumors upon
      inoculation into athymic nude mice. Specifically, alpha-irradiation induced
      damage to both mitochondrial DNA (mtDNA) and mitochondrial functions in
      transformed cells as evidenced by increased mtDNA copy number and common
      deletion, decreased oxidative phosphorylation activity as measured by cytochrome
      C oxidase (COX) activity and oxygen consumption. There was a linear correlation
      between mtDNA copy number, common deletion, COX activity and cellular
      transformation represented by soft agar colony formation and c-Myc expression.
      These results suggest that mitochondria are associated with neoplastic
      transformation of SAEC cells induced by alpha-particles, and that the oncogenesis
      process may depend not only on the genomes inside the nucleus, but also on the
      mitochondrial DNA outside the nucleus.

PMID- 22644784
TI  - IL-1beta-mediated up-regulation of DEC1 in human gingiva cells via the Akt
      pathway.
AB  - Growing evidence indicates that inflammation is a contributing factor leading to
      cancer development. However, pathways involved in this progression are not well
      understood. The involvement of DEC1 in cancer prompted us to examine whether pro
      inflammatory cytokine interleukin-1beta (IL-1beta) induces the expression of DEC1
      in oral inflammation. We found that IL-1beta up-regulated DEC1 and hypoxia
      inducible factor-1alpha (HIF-1alpha) protein and elevated the HIF-1alpha
      responsive gene vascular endothelial growth factor (VEGF) expression in human
      primary gingival cells. HIF-1alpha and DEC1 immunoreactivity were significantly
      higher in the cases of gingival inflammation. We demonstrate that IL-1beta up
      regulates DEC1 and HIF-1alpha protein through a classical inflammatory signaling
      pathway involving Akt. Our data strongly suggest that PI-3K-Akt is an upstream
      participant in IL-1beta-mediated DEC1 and HIF-1alpha induction. This is supported
      by the following data: (1) IL-1beta induces 473 serine phosphorylation of Akt;
      (2) IL-1beta-mediated Akt activation occurs in a PI-3K-dependent manner, and
      specific inhibition of PI-3K prevents Akt phosphorylation; and (3) inhibition of
      Akt prevents IL-1beta-mediated DEC1 and HIF-1alpha induction. Taken together,
      these results suggest that DEC1 is one of the important transcription factors in
      inflammation.

PMID- 22644785
TI  - Intramuscular nerve distribution pattern of the adductor longus and gracilis
      muscles demonstrated with Sihler staining: guidance for botulinum toxin
      injection.
AB  - INTRODUCTION: The aims of this study were to clarify the intramuscular branching
      patterns and arborizing area of hip adductor muscles with reference to surface
      landmarks on the thigh and to thus suggest effective and safe injection points
      for botulinum neurotoxin (BoNT). METHODS: Ten gracilis and 10 adductor longus
      specimens were subjected to Sihler staining to reveal intramuscular nerve
      arborization patterns, and findings were matched with and referred to surface
      landmarks. Using these results, we determined the optimal location for BoNT
      injection in hip adductors in relation to the long axis of the femur. RESULTS:
      The corrected, most dense areas of innervation in adductor longus and gracilis
      were typically 30-50% and 40-50% from the anterior superior iliac spine (ASIS)
      along the vertical line of the femur, respectively. CONCLUSIONS: The most
      effective and safest point for BoNT injection into adductor muscles appears to be
      between 35% and 50% from ASIS, where neuromuscular junctions are most densely
      distributed.

PMID- 22644786
TI  - Potentiated activation of VLA-4 and VLA-5 accelerates proplatelet-like formation.
AB  - Fibronectin (FN) plays important roles in the proliferation, differentiation, and
      maintenance of megakaryocytic-lineage cells through FN receptors. However,
      substantial role of FN receptors and their functional assignment in proplatelet
      like formation (PPF) of megakaryocytes are not yet fully understood. Herein, we
      investigated the effects of FN receptors on PPF using the CHRF-288 human
      megakaryoblastic cell line, which expresses VLA-4 and VLA-5 as FN receptors. FN
      and phorbol 12-myristate 13-acetate (PMA) were essential for inducing PPF in CHRF
      288 cells. Blocking experiments using anti-beta1-integrin monoclonal antibodies
      indicated that the adhesive interaction with FN via VLA-4 and VLA-5 were required
      for PPF. PPF induced by FN plus PMA was accelerated when CHRF-288 cells were
      enforced adhering to FN by TNIIIA2, a peptide derived from tenascin-C, which we
      recently found to induce beta1-integrin activation. Adhesion to FN enhanced PMA
      stimulated activation of extracellular signal-regulated protein kinase 1 (ERK1)/2
      and enforced adhesion to FN via VLA-4 and VLA-5 by TNIIIA2-accelerated activation
      of ERK1/2 with FN plus PMA. However, c-Jun amino-terminal kinase 1 (JNK1), p38,
      and phosphoinositide-3 kinase (PI3K)/Akt were not stimulated by FN plus PMA, even
      with TNIIIA2. Thus, the enhanced activation of ERK1/2 by FN, PMA plus TNIIIA2 was
      responsible for acceleration of PPF with FN plus PMA.

PMID- 22644788
TI  - Synaptic conditions for auto-associative memory storage and pattern completion in
      Jensen et al.'s model of hippocampal area CA3.
AB  - Jensen et al. (Learn Memory 3(2-3):243-256, 1996b) proposed an auto-associative
      memory model using an integrated short-term memory (STM) and long-term memory
      (LTM) spiking neural network. Their model requires that distinct pyramidal cells
      encoding different STM patterns are fired in different high-frequency gamma
      subcycles within each low-frequency theta oscillation. Auto-associative LTM is
      formed by modifying the recurrent synaptic efficacy between pyramidal cells. In
      order to store auto-associative LTM correctly, the recurrent synaptic efficacy
      must be bounded. The synaptic efficacy must be upper bounded to prevent re-firing
      of pyramidal cells in subsequent gamma subcycles. If cells encoding one memory
      item were to re-fire synchronously with other cells encoding another item in
      subsequent gamma subcycle, LTM stored via modifiable recurrent synapses would be
      corrupted. The synaptic efficacy must also be lower bounded so that memory
      pattern completion can be performed correctly. This paper uses the original model
      by Jensen et al. as the basis to illustrate the following points. Firstly, the
      importance of coordinated long-term memory (LTM) synaptic modification. Secondly,
      the use of a generic mathematical formulation (spiking response model) that can
      theoretically extend the results to other spiking network utilizing threshold
      fire spiking neuron model. Thirdly, the interaction of long-term and short-term
      memory networks that possibly explains the asymmetric distribution of spike
      density in theta cycle through the merger of STM patterns with interaction of LTM
      network.

PMID- 22644790
TI  - A two-year prospective study of psychache and its relationship to suicidality
      among high-risk undergraduates.
AB  - OBJECTIVES: Edwin Shneidman's theory of suicide was tested by examining the
      relationships of depression, hopelessness, and psychache with suicide ideation,
      longitudinally. DESIGN: Forty-one high-risk students who were suicide ideators
      completed questionnaires measuring depression, hopelessness, psychache, and
      suicide ideation at baseline and 2 years later. RESULTS: Regression analyses
      showed that at baseline and at follow-up, psychache was the only unique
      contributor to the statistical prediction of suicide ideation. When examining
      change over time, change in psychache was the only factor that added significant
      unique variance to the prediction of change in suicide ideation. CONCLUSIONS:
      Results support Shneidman's assertion that other psychological factors, such as
      depression and hopelessness, are only important to suicide insofar as their
      relationship with psychache, and that psychache and suicide ideation co-vary over
      time.

PMID- 22644793
TI  - Three-dimensional pharmacophore design and biochemical screening identifies
      substituted 1,2,4-triazoles as inhibitors of the annexin A2-S100A10 protein
      interaction.
AB  - Protein interactions are increasingly appreciated as targets in small-molecule
      drug discovery. The interaction between the adapter protein S100A10 and its
      binding partner annexin A2 is a potentially important drug target. To obtain
      small-molecule starting points for inhibitors of this interaction, a three
      dimensional pharmacophore model was constructed from the X-ray crystal structure
      of the complex between S100A10 and annexin A2. The pharmacophore model represents
      the favourable hydrophobic and hydrogen bond interactions between the two
      partners, as well as spatial and receptor site constraints (excluded volume
      spheres). Using this pharmacophore model, UNITY flex searches were carried out on
      a 3D library of 0.7 million commercially available compounds. This resulted in
      568 hit compounds. Subsequently, GOLD docking studies were performed on these
      hits, and a set of 190 compounds were purchased and tested biochemically for
      inhibition of the protein interaction. Three compounds of similar chemical
      structure were identified as genuine inhibitors of the binding of annexin A2 to
      S100A10. The binding modes predicted by GOLD were in good agreement with their
      UNITY-generated conformations. We synthesised a series of analogues revealing
      areas critical for binding. Thus computational predictions and biochemical
      screening can be used successfully to derive novel chemical classes of protein
      protein interaction blockers.

PMID- 22644792
TI  - Gender differences in adiponectin modulation of cardiac remodeling in mice
      deficient in endothelial nitric oxide synthase.
AB  - Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a
      leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS),
      an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte
      derived secretory factor, are associated with cardiac remodeling. Deficiency of
      eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso
      protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized
      that increased levels of adiponectin would alleviate cardiac pathology resulting
      from eNOS deficiency, while decreased levels of adiponectin would exacerbate the
      pathology. Male and female mice, deficient in eNOS, and either lacking or over
      expressing adiponectin, were fed high fat diet (HFD) or normal chow. Cardiac
      magnetic resonance imaging was performed to serially assess heart morphology and
      function up to 40 weeks of age. Thirty-two weeks of HFD feeding led to
      significantly greater LV mass in male mice deficient in eNOS and either lacking
      or over-expressing adiponectin. Heart function was significantly reduced when the
      mice were deficient in either eNOS, adiponectin or both eNOS and adiponectin; for
      female mice, heart function was only reduced when both eNOS and adiponectin were
      lacking. Thus, while over-expression of adiponectin in the eNOS deficient HFD fed
      male mice preserved function at the expense of significantly increased LV mass,
      female mice were protected from decreased function and increased LVH by over
      expression of adiponectin. Our results demonstrate a sexual dimorphism in
      response of the heart to alterations in eNOS and adiponectin during high fat
      feeding and suggest that adiponectin might require eNOS for some of its metabolic
      effects.

PMID- 22644794
TI  - Risk factors associated with the need for a tracheostomy in extremely low birth
      weight infants.
AB  - In an attempt to determine the risk factors associated with the need for a
      tracheostomy in extremely low birth weight (ELBW) infants, a retrospective, case
      control study was conducted (each infant with a tracheostomy [case] was matched
      to two controls). Medical records were reviewed for patients' characteristics,
      risk factors for tracheostomy and outcome. During the study period (June 1996 to
      Dec 2010), 934 ELBW infants were admitted to our institution and nine infants had
      a tracheostomy and were matched to 18 controls. There were no differences in
      birth weight (BW) and gestation age (GA) between cases and controls (828.1 +/-
      136.2 g vs. 822.0 +/- 140.9 g [P = 0.91] and 26.6 +/- 1.8 weeks vs. 26.5 +/- 1.6
      weeks [P = 0.88], respectively). In comparison to their controls, infants with a
      tracheostomy had a higher rate of intubation (median 13 [11-15] vs. 3 [2-5], P <=
      0.001), a higher rate of total intubation attempts (median 18 [13-21] vs. 5.5 [3
      7], P = 0.001), and more days of mechanical ventilation prior to their
      tracheostomy (mean 100.7 +/- 27.7 vs. 29.2 +/- 19.8 days [P < 0.001]). Also
      infants with a tracheostomy had a higher rate of non-congenital upper airway
      obstruction (55% [5/9] vs. 0% [0/18]; P = 0.001), a higher rate of chronic lung
      disease (100% [9/9] vs. 5% [1/18]; P < 0.001) and a higher mortality (44% [4/9]
      vs. 0% [0/18]; P = 0.007) than their controls. In conclusion, chronic lung
      disease, multiple intubations and intubation attempts, duration of mechanical
      ventilation, and non-congenital upper airway obstruction are risk factors
      associated with tracheostomies in ELBW infants.

PMID- 22644795
TI  - Diffusion tensor MRI to assess skeletal muscle disruption following eccentric
      exercise.
AB  - INTRODUCTION: Structural evidence of exercise-induced muscle disruption has
      traditionally involved histological analysis of muscle tissue obtained by needle
      biopsy, however, there are multiple limitations with this technique. Recently,
      diffusion tensor magnetic resonance imaging (DT-MRI) has been successfully
      demonstrated to noninvasively assess skeletal muscle abnormalities induced by
      traumatic injury. METHODS: To determine the potential for DT-MRI to detect
      musculoskeletal changes after a bout of eccentric exercise, 10 healthy men
      performed 300 eccentric actions on an isokinetic dynamometer. DT-MRI measurements
      and muscle biopsies from the vastus lateralis were obtained before and 24 h post
      exercise. RESULTS: Z-band streaming was higher 24 h post-exercise compared with
      baseline (P < 0.05). The histological indices of damage coincided with changes in
      DT-MRI parameters of fractional anisotropy (FA) and apparent diffusion
      coefficient; reflecting altered skeletal muscle geometry (P < 0.05). Z-band
      streaming quantified per fiber correlated with FA (r = -0.512; P < 0.05).
      CONCLUSIONS: DT-MRI can detect changes in human skeletal muscle structure
      following eccentric exercise.

PMID- 22644789
TI  - A composite score for executive functioning, validated in Alzheimer's Disease
      Neuroimaging Initiative (ADNI) participants with baseline mild cognitive
      impairment.
AB  - The Alzheimer's Disease Neuroimaging Initiative (ADNI) measures abilities broadly
      related to executive function (EF), including WAIS-R Digit Symbol Substitution,
      Digit Span Backwards, Trails A and B, Category Fluency, and Clock Drawing. This
      study investigates whether a composite executive function measure based on these
      multiple indicators has better psychometric characteristics than the widely used
      individual components. We applied item response theory methods to 800 ADNI
      participants to derive an EF composite score (ADNI-EF) from the above measures.
      We then compared ADNI-EF with component measures in 390 longitudinally-followed
      participants with mild cognitive impairment (MCI) with respect to: (1) Ability to
      detect change over time; (2) Ability to predict conversion to dementia; (3)
      Strength of cross-sectional association with MRI-derived measures of structures
      involved in frontal systems, and (4) Strength of baseline association with
      cerebrospinal fluid (CSF) levels of amyloid beta1-42, total tau, and
      phosphorylated tau(181P). ADNI-EF showed the greatest change over time, followed
      closely by Category Fluency. ADNI-EF needed a 40 % smaller sample size to detect
      change. ADNI-EF was the strongest predictor of AD conversion. ADNI-EF was the
      only measure significantly associated with all the MRI regions, though other
      measures were more strongly associated in a few of the regions. ADNI-EF was
      associated with all the CSF measures. ADNI-EF appears to be a useful composite
      measure of EF in MCI, as good as or better than any of its composite parts. This
      study demonstrates an approach to developing a psychometrically sophisticated
      composite score from commonly-used tests.

PMID- 22644796
TI  - The impact of bevacizumab on temozolomide concentrations in intracranial U87
      gliomas.
AB  - PURPOSE: An important question in the sequencing of anti-cancer therapies in
      patients with glioblastoma (GBM) is whether concurrent anti-angiogenesis
      therapies improve or impair brain concentrations of concomitantly administered
      cytotoxic therapies. The purpose of this study is to assess the intratumoral
      disposition of temozolomide (TMZ) via microdialysis before and after bevacizumab
      in an intracranial GBM xenograft model. METHODS: Microdialysis probes were placed
      within tumor and contralateral brain in athymic rats bearing U87 intracerebral
      gliomas. TMZ (50 mg/kg oral) was administered 10 days thereafter. Extracellular
      fluid (ECF) was collected for 6 h. BEV was administered (10 mg/kg IV), and TMZ
      was re-dosed (50 mg/kg oral) 36 h thereafter with additional ECF collection. All
      ECF samples were assessed for TMZ concentration with liquid chromatography-tandem
      mass spectrometry. RESULTS: Tumor TMZ mean area under the concentration-time
      curve (AUC(0-infinity)) was 3.35 MUg h/mL pre-BEV. Post-BEV, tumor mean TMZ AUC(0
      infinity) was 3.98 MUg h/mL. In non-tumor brain, mean TMZ AUC(0-infinity) pre-BEV
      was 3.22 MUg h/mL and post-BEV was 3.34 MUg h/mL. CONCLUSIONS: There were no
      statistically significant changes in TMZ pharmacokinetics before or after BEV in
      the athymic rat U87 intracranial glioma model. BEV and TMZ are being investigated
      as a combination therapy in several ongoing studies for patients with glioma.
      These data reassuringly suggest that BEV does not significantly change the ECF
      tumor concentrations of TMZ in either tumor-bearing or normal brain when dosed 36
      h prior to TMZ.

PMID- 22644797
TI  - Evaluation of the effect of food on the pharmacokinetics of axitinib in healthy
      volunteers.
AB  - PURPOSE: To evaluate the effect of food on axitinib pharmacokinetics in healthy
      volunteers with two different crystal polymorphs. METHODS: Two separate open
      label, randomized, single-dose, three-period, crossover trials were conducted.
      Study I, conducted first using 5-mg axitinib Form IV film-coated immediate
      release (FCIR) tablets, enrolled 18 subjects to compare fed versus fasted states
      and 24 subjects to evaluate the effect of timing of food consumption on axitinib
      pharmacokinetics. Study II enrolled 30 subjects to assess the effect of food
      using 5-mg axitinib Form XLI FCIR tablets. Subjects received axitinib after
      overnight fasting, with limited fasting or, depending on the study design, after
      consuming high-fat, high-calorie or moderate-fat, standard-calorie meals.
      RESULTS: For Form IV FCIR, compared with overnight fasting, axitinib plasma
      exposure [area under the concentration curve (AUC)] was decreased 23 % when
      administered with food. For Form XLI FCIR, mean axitinib plasma AUC and maximum
      plasma concentration (C(max)) were 19 and 11 % higher, respectively, with a high
      fat, high-calorie meal compared with overnight fasting. When Form XLI FCIR was
      administered with moderate-fat, standard-calorie meal, AUC and C(max) were 10 and
      16 % lower compared with overnight fasting. Both formulations were well
      tolerated. Adverse events, mostly gastrointestinal (7 % with Form IV FCIR and 13
      % with Form XLI FCIR), were mild to moderate in both studies. CONCLUSIONS: While
      axitinib Form IV FCIR was associated with higher plasma exposure after overnight
      fasting, axitinib Form XLI FCIR can be administered with or without food as
      differences in axitinib pharmacokinetics under the two conditions were not
      clinically meaningful.

PMID- 22644798
TI  - Farletuzumab, an anti-folate receptor alpha antibody, does not block binding of
      folate or anti-folates to receptor nor does it alter the potency of anti-folates
      in vitro.
AB  - PURPOSE: Folate is a cofactor in the synthesis of purines and pyrimidines; folate
      analogs are potent cytotoxic drugs. Folate receptor alpha (FRalpha), a protein
      mediating cellular accumulation of folate (and anti-folates), has limited
      expression in normal tissues and is overexpressed by numerous carcinomas. Limited
      distribution and high affinity for folic acid have resulted in the development of
      antibodies or the use of folic acid coupled to toxins or radionuclides as
      therapeutic and imaging agents. Farletuzumab is an anti-FRalpha antibody in
      clinical trials for ovarian and non-small cell lung cancers. Our goal was to
      evaluate the effect of farletuzumab on binding and uptake of folates and anti
      folates and the potency of anti-folates in vitro. METHODS: Direct binding and
      uptake of radiolabeled folates and anti-folates and the assessments of drug
      concentration of drug that inhibited cell growth 50 % (IC(50)) in vitro in the
      presence or absence of antibody. RESULTS: Farletuzumab did not block membrane
      binding of radiolabeled folic acid, 5-methyltetrahydrofolate, pemetrexed, and
      other anti-folates; folic acid blocked >95 %. Farletuzumab had a minimal effect
      on the cytoplasmic accumulation of 5-methyltetrahydrofolate or pemetrexed; folic
      acid had a considerable but variable effect on the different cell lines. As a
      single agent, farletuzumab did not affect cell viability or the IC(50) of
      pemetrexed and other anti-folates in vitro. CONCLUSIONS: Farletuzumab does not
      block FRalpha binding of folates and anti-folates, minimally retards folate
      delivery via FRalpha-mediated transport, and minimally retards the growth of
      cells in vitro. Concomitant use of farletuzumab and pemetrexed is not
      contraindicated.

PMID- 22644799
TI  - A phase I study of temsirolimus plus carboplatin plus paclitaxel for patients
      with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC).
AB  - PURPOSE: The mammalian target of rapamycin complex 1 (mTORC1) is aberrantly
      activated in many head and neck squamous cell carcinomas (HNSCCs). This phase I
      study combines the mTORC1 inhibitor temsirolimus with carboplatin and paclitaxel.
      METHODS: This was a single institution phase I study for patients with R/M HNSCC
      with a standard 3 + 3 design. Three doses of temsirolimus were planned: 15, 20,
      and 25 mg. Due to excessive toxicity with the original study regimen, the
      protocol was amended to carboplatin AUC 1.5, paclitaxel 80 mg/m(2), and
      temsirolimus (according to dose escalation plan), all on days 1 and 8 of a 21-day
      cycle. RESULTS: 18 patients (14 male, 4 female) enrolled, with median age 56
      years (range 33-78). The most common toxicities were anemia, leukopenia,
      thrombocytopenia, and hyperglycemia. Among all patients treated, the confirmed
      objective partial response (cPR) rate was 22 %. DLT was not exceeded among 6
      patients treated at dose level 3 of the revised protocol, and 4 of 6 subjects
      treated at this dose level had cPRs. CONCLUSION: The phase II recommended regimen
      is temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m(2), all on
      days 1 and 8 of a 21-day cycle. A phase II study of this regimen in R/M HNSCC is
      ongoing.

PMID- 22644800
TI  - When a reference value makes all the difference.

PMID- 22644801
TI  - Implications of cavotricuspid isthmus block complicating ablation of a
      posteroseptal accessory pathway.

PMID- 22644802
TI  - Lifestyle after bariatric surgery: a multicenter, prospective cohort study in
      pregnant women.
AB  - BACKGROUND: To ensure a good pregnancy outcome after bariatric surgery, a healthy
      life-style and a multidisciplinary prenatal follow-up is recommended. The aim of
      this prospective multicenter trial was to compare diet quality and physical
      activity (PA) of pregnant women with bariatric surgery with current lifestyle
      recommendations. METHODS: Pregnant women (>18 years, prepregnancy BMI 28 +/- 6
      kg/m2, 39 % nulliparae, 25 % smokers) with a history of bariatric surgery were
      recruited and allocated to two groups according to surgery type: restrictive (N =
      18) and bypass group (N = 31). One 7-day dietary record and one Kaiser
      questionnaire on PA were collected during the first and second trimester. Dietary
      quality was assessed using the Healthy Eating Index. RESULTS: The diet quality
      did not change during pregnancy (restrictive group p = 0.050; bypass group p =
      0.975) and was comparable between groups (first trimester p = 0.426; second
      trimester p = 0.937). During the first trimester, 15 % of the pregnant women had
      a healthy diet quality, 82 % had a diet that needed improvement, and 3 % had a
      poor diet quality. This was independent of surgery type and was comparable in the
      second trimester (p = 0.525). No difference between groups was observed for the
      PA level, but the PA level in the bypass group significantly decreased from the
      first to the second trimester (p = 0.033). CONCLUSIONS: Nutritional advice and
      lifestyle coaching in this high-risk population seems recommendable since only 15
      % of the pregnant women had a healthy diet quality, 25 % was smoking at the
      beginning of pregnancy, and the reported PA levels were low.

PMID- 22644803
TI  - Ischemia-induced copper loss and suppression of angiogenesis in the pathogenesis
      of myocardial infarction.
AB  - Myocardial ischemia is a primary cause for the loss of vital components such as
      cardiomyocytes in the heart, leading to myocardial infarction and eventual
      cardiac dysfunction or heart failure. Suppressed angiogenesis plays a determinant
      role in the pathogenesis of myocardial infarction. In response to myocardial
      ischemia, hypoxia-inducible factor-1alpha and 2alpha (HIF-1alpha and HIF-2alpha)
      accumulate in cardiomyocytes and other cell types. This would up-regulate the
      expression of genes involved in angiogenesis such as vascular endothelial growth
      factor (VEGF); however, it is often observed that the angiogenic capacity is
      suppressed rather than enhanced. Ischemic toxicity, which has not been fully
      recognized, is highly responsible for the compromised angiogenic capacity. One of
      the toxic effects resulting from myocardial ischemia is the loss of copper
      content in the heart. Although the reason for this loss has not been elucidated,
      the essential role of copper in the regulation of HIF-1 transcriptional activity
      has been described. Copper does not affect the accumulation of HIF-1alpha in the
      cell, but is required for the HIF-1 transcriptional complex formation and its
      interaction with the hypoxia-responsive element in target genes. Copper
      supplementation can stimulate the transcriptional activity of HIF-1 and restore
      angiogenic capacity, leading to increased capillary density in the heart. The
      recognition of ischemic toxicity and the effort to overcome the toxic effect
      would help develop alternative approaches in the treatment of ischemic heart
      disease.

PMID- 22644804
TI  - PI3K/Akt pathway mediates high glucose-induced lipid accumulation in human renal
      proximal tubular cells via spliced XBP-1.
AB  - In the present study, we investigated the effect of X-box-binding protein-1 (XBP
      1) splicing on lipogenesis in high glucose-stimulated human renal proximal
      tubular cell line (HKC). The results revealed that high glucose promoted the
      splicing of XBP-1, concomitant with up-regulation of lipogenic genes including
      fatty acid synthase, acetyl-CoA carboxylase, adipocyte differentiation-related
      protein, and cellular triglyceride. Again, silence of XBP-1 with shRNA vector
      inhibited high glucose-caused increased lipogenesis. Furthermore, we confirmed
      that the inhibition of phosphotidyl inositol 3-kinase (PI3K)/Akt pathway with
      LY294002 or Akt shRNA vector blocked the effect of high glucose on XBP-1 splicing
      and cellular triglyceride. These above data suggest that spliced XBP-1 mediates
      high glucose-induced lipid accumulation in HKC cells and PI3K/Akt pathway may be
      involved in high glucose-caused XBP-1 splicing.

PMID- 22644805
TI  - Quantitative ultrasound of the tongue and submental muscles in children and young
      adults.
AB  - INTRODUCTION: The purpose of this study was to assess the feasibility of
      quantitative muscle ultrasound (QMUS) to visualize oral muscles and to establish
      normative data for muscle thickness and echo intensity of submental and tongue
      muscles in healthy children and young adults. The data were compared with those
      of 5 patients with Duchenne muscular dystrophy (DMD). METHODS: Ultrasound images
      from the suprahyoid region and from the surface of the tongue were made in 53
      healthy subjects aged 5 to 30 years. RESULTS: All measurements were feasible in
      all subjects and patients with good reproducibility except for the mylohyoid
      muscle. Muscle thickness depended on height, and echo intensity depended on
      weight. Our findings suggest gradual involvement of oral muscles in DMD.
      CONCLUSIONS: QMUS in oral muscles is feasible in healthy children, adults and
      patients with DMD. These data show that it is possible to differentiate between
      healthy persons and patients with DMD.

PMID- 22644806
TI  - Chordoid glioma: a rare suprasellar mass.

PMID- 22644807
TI  - An unusual presentation of a vein of Galen thrombosis.

PMID- 22644808
TI  - Effect of salicylate on the large GABAergic neurons in the inferior colliculus of
      rats.
AB  - Salicylate, the anti-inflammatory component of aspirin, induces transient
      tinnitus and hearing loss in clinical and animal experiments. However, the
      affected sites and mechanisms of generation remain unclear. Recently, down
      regulation of inhibitory transmission mediated by gamma-aminobutyric acid type A
      receptors was suggested to be crucial in generating tinnitus. However, the cell
      specific pathways involved in this process were far from being understood. Here,
      we describe changes of inhibitory neurotransmitter, receptor, and glutamatergic
      axosomatic terminals in certain large GABAergic neurons (LGNs) in the inferior
      colliculus of rats treated with high doses of salicylate. Based on these results,
      we suggest that salicylate may affect inhibitory projection pathways from the
      inferior colliculus to the auditory cortex and lead to neural hyperactivity,
      perhaps by affecting the function of the LGNs.

PMID- 22644809
TI  - Mesenchymal stromal cell phenotype is not influenced by confluence during culture
      expansion.
AB  - BACKGROUND: Accumulating preclinical and clinical evidence indicates that human
      mesenchymal stromal cells (MSCs) are good candidates for cell therapy. For
      clinical applications of MSCs extensive in vitro expansion is required to obtain
      an adequate number of cells. It is evident that the pursuit for cell quantity
      must not affect quality, but it is also a fact that in vitro culture conditions
      affect MSC phenotype. One possible variable is the degree of cell confluence
      during expansion. METHODS: We investigate the influence of cell density on
      homogeneity and differentiation during culture expansion of un-stimulated MSCs
      isolated from the bone marrow in DMEM and fetal bovine serum (FBS). MSC
      morphology, phenotype and differentiation were investigated weekly during 5 weeks
      culture expansion using electron microscopy, flow cytometry, immunocytochemistry,
      qualitative RT-PCR and quantitative Q-PCR. RESULTS: The morphological observation
      and the phenotypic analyses showed that MSCs after 3 weeks cultivation
      constituted a phenotypically homogenous MSC cell population, which at low levels
      expressed genes for different cell lineages, confirming their multilineage
      plasticity, without actual differentiation. This phenotype persisted independent
      of increasing cell densities. DISCUSSION: These data demonstrate that MSC
      characteristics and plasticity can be maintained during culture expansion from
      bone marrow mononuclear cells to MSCs and that a homogeneous phenotype of
      undifferentiated MSCs which persists independent of cell density can be used for
      clinical therapies.

PMID- 22644810
TI  - Analysis of fatty acids in 12 Mediterranean fish species: advantages and
      limitations of a new GC-FID/GC-MS based technique.
AB  - When fatty acids in fish are analyzed, results in percentage form (profile
      analysis) are mostly reported. However, the much more useful results expressed as
      mg/100 g (absolute analysis) is the main information required. Absolute methods
      based on calibration curves are of good accuracy but with a high degree of
      complexity if applied to a great number of analytes. Procedures based on the
      sequence profile analysis-total FA determination-absolute analysis may be
      suitable for routine use, but suffer from a number of uncertainties that have
      never been really resolved. These uncertainties are mainly related to the profile
      analysis. In fact, most profile analyses reported in the literature disagree
      about the number and type of fatty acids monitored as well as about the total
      percentage to assign to their sum so leading to possible inaccuracies; in
      addition the instrumental response factor for all FAME (fatty acid methyl esters)
      is often considered as a constant, but this is not exactly true. In this work, a
      set of 24 fatty acids was selected and studied on 12 fish species in the
      Mediterranean area (variable in lipid content and month of sampling): in our
      results, and in these species, this set constitutes, on average, 90 +/- 3 % of
      the total fatty acid content. Moreover the error derived from the assumption of a
      unique response factor was investigated. Two different detection techniques (GC
      FID and GC-MS) together with two capillary columns (different in length and
      polarity) were used in order to acquire complementary data on the same sample.
      With the protocol here proposed absolute analyses on the 12 cited species are
      easily achievable by the total FA determination procedure. The accuracy of this
      approach is good in general, but in some cases (DHA for example) is lower than
      the accuracy of calibration-based methods. The differences were evaluated on a
      case by case basis.

PMID- 22644811
TI  - Arrangement of nuclear structures is not transmitted through mitosis but is
      identical in sister cells.
AB  - Although it is well known that chromosomes are non-randomly organized during
      interphase, it is not completely clear whether higher-order chromatin structure
      is transmitted from mother to daughter cells. Therefore, we addressed the
      question of how chromatin is rearranged during interphase and whether
      heterochromatin pattern is transmitted after mitosis. We additionally tested the
      similarity of chromatin arrangement in sister interphase nuclei. We noticed a
      very active cell rotation during interphase, especially when histone
      hyperacetylation was induced or transcription was inhibited. This natural
      phenomenon can influence the analysis of nuclear arrangement. Using
      photoconversion of Dendra2-tagged core histone H4 we showed that the distribution
      of chromatin in daughter interphase nuclei differed from that in mother cells.
      Similarly, the nuclear distribution of heterochromatin protein 1beta (HP1beta)
      was not completely identical in mother and daughter cells. However, identity
      between mother and daughter cells was in many cases evidenced by nucleolar
      composition. Moreover, morphology of nucleoli, HP1beta protein, Cajal bodies,
      chromosome territories, and gene transcripts were identical in sister cell
      nuclei. We conclude that the arrangement of interphase chromatin is not
      transmitted through mitosis, but the nuclear pattern is identical in naturally
      synchronized sister cells. It is also necessary to take into account the
      possibility that cell rotation and the degree of chromatin condensation during
      functionally specific cell cycle phases might influence our view of nuclear
      architecture.

PMID- 22644812
TI  - Timing of the administration of suramin treatment after muscle injury.
AB  - INTRODUCTION: It has been reported that suramin treatment can improve muscle
      healing; however, details about optimizing the dosing requirements remain
      unclear. The purpose of this study was to determine the optimal timing of suramin
      administration and investigate the effects it had on the expression of myostatin,
      follistatin, and muscle vascularity after muscle injury. METHODS: Contusion
      injured muscles of mice were treated with suramin at 1, 2, or 3 weeks post-injury
      and evaluated histologically and physiologically at 1, 2, and 10 days after
      injection. RESULTS: Suramin treatment initiated at 2 weeks post-injury was
      observed to promote muscle regeneration and muscle strength, and to decrease
      fibrosis. Suramin reduced myostatin expression and increased follistatin
      expression and vascularity in injured skeletal muscle. CONCLUSIONS: Suramin's
      positive effect on muscle regeneration is thought to be due to its enhancement of
      follistatin expression which increases neoangiogenesis and inhibits myostatin's
      promotion of fibrosis.

PMID- 22644813
TI  - Apropos "Fatal dengue hemorrhagic fever imported into Germany".

PMID- 22644814
TI  - Socioeconomic status and stress in Mexican-American women: a multi-method
      perspective.
AB  - Stress is a hypothesized pathway in socioeconomic status (SES)-physical health
      associations, but the available empirical data are inconsistent. In part, this
      may reflect discrepancies in the approach to measuring stress across studies, and
      differences in the nature of SES-stress associations across demographic groups.
      We examined associations of SES (education, income) with general and domain
      specific chronic stressors, stressful life events, perceived stress, and
      stressful daily experiences in 318 Mexican-American women (40-65 years old).
      Women with higher SES reported lower perceived stress and fewer low-control
      experiences in everyday life (ps < .05), but greater chronic stress (education
      only, p < .05). Domain-specific analyses showed negative associations of income
      with chronic housing and financial stress (ps < .05), but positive associations
      of SES with chronic work and caregiving stress (all ps < .05 except for income
      and caregiving stress, p < .10). Sensitivity analyses showed that most SES-stress
      associations were consistent across acculturation levels. Future research should
      adopt a multi-dimensional assessment approach to better understand links among
      SES, stress, and physical health, and should consider the sociodemographic
      context in conceptualizing the role of stress in SES-related health inequalities.

PMID- 22644815
TI  - Arachidonic acid induces an increase of beta-1,4-galactosyltransferase I
      expression in MDA-MB-231 breast cancer cells.
AB  - Arachidonic acid (AA) is a common dietary n-6 cis polyunsaturated fatty acid that
      under physiological conditions is present in an esterified form in cell membrane
      phospholipids, and it might be present in the extracellular microenvironment. AA
      and its metabolites are implicated in FAK activation and cell migration in MDA-MB
      231 breast cancer cells, and an epithelial-to-mesenchymal-like transition process
      in mammary non-tumorigenic epithelial cells MCF10A. During malignant
      transformation is present an altered expression of glycosiltransferases, which
      promote changes on the glycosilation of cell-surface proteins. The beta-1,4
      galactosyltransferase I (GalT I) is an enzyme that participates in a variety of
      biological functions including cell growth, migration, and spreading. However,
      the participation of AA in the regulation of GalT I expression and the role of
      this enzyme in the cell adhesion process in breast cancer cells remains to be
      investigated. In the present study, we demonstrate that AA induces an increase of
      GalT I expression through a PLA2alpha, Src, ERK1/2, and LOXs activities-dependent
      pathway in MDA-MB-231 breast cancer cells. Moreover, MDA-MB-231 cells adhere to
      laminin via GalT I expression and pretreatment of cells with AA induces an
      increase of cell adhesion to laminin. In conclusion, our findings demonstrate,
      for the first time, that AA promotes an increase of GalT I expression through an
      AA metabolism, Src and ERK1/2 activities-dependent pathway, and that GalT I plays
      a pivotal role in cell adhesion to laminin in MDA-MB-231 breast cancer cells.

PMID- 22644816
TI  - A giant neuroendocrine tumor of the thymus gland causing superior vena cava
      syndrome.
AB  - We describe the case of a 37-year-old man with a rare giant thymic neuroendocrine
      tumor. The patient presented with a swelling of the neck associated with superior
      vena cava syndrome and underwent stent implantation in the right innominate vein
      (brachiocephalic vein). Computed tomography imaging revealed a large tumor of the
      mediastinum, measuring 15 * 10 * 12 cm. CT-guided core-needle biopsy for
      histology revealed a thymic carcinoid. Surgical resection of the tumor and repair
      with interposition of a 14-mm Gore-Tex prosthesis between the left innominate
      vein and the right atrial appendage were performed. Histopathological analysis
      classified the tumor as an atypical thymic carcinoid. Postoperative course was
      uneventful. Since complete resection could not be achieved, the patient received
      two cycles of peptide-receptor radionuclide therapy followed by conventional
      radiotherapy, and remains symptom-free at 12 months after surgery.

PMID- 22644817
TI  - Video-assisted thoracic surgery lobectomy for lung cancer in a patient with
      complete situs inversus.
AB  - Complete situs inversus is a rare abnormality of autosomal recessive inheritance;
      it requires particular care during surgery, because the viscus anatomy is a
      mirror image of the normal anatomy. Reports of surgery for lung cancer in cases
      of complete situs inversus are very rare. Here, we report a case of lobectomy for
      lung cancer of the right lower lobe performed using video-assisted thoracic
      surgery (VATS) in a patient with complete situs inversus. We emphasize the
      importance of careful examination of the relationship between the bronchus,
      pulmonary artery, and pulmonary vein in the hilum of the lung in cases of
      complete situs inversus requiring lung resection for cancer; this is even more
      necessary when VATS is performed.

PMID- 22644818
TI  - Hyperthemia after cardiac surgery due to ascariasis in a child: report of a case.
AB  - Ascaris lumbricoides is the most common parasite affecting humans, especially in
      countries and regions with lower socio-economic conditions. A 2-year-old female
      child underwent right pulmonary angioplasty using cardiopulmonary bypass. Serious
      hyperthermia continued after surgery, and, therefore, a re-exploration of the
      mediastinum was performed because mediastinitis was suspected. No evidence of
      wound infection was revealed. Ascaris lumbricoides was subsequently isolated from
      her stool. The patient had no further hyperthermia throughout her hospitalization
      and was discharged uneventfully on post-operative day 12. The probable origin of
      the fever was an A. lumbricoides infection and ascariasis may cause the
      occurrence of serious hyperthermia during the perioperative period. Ascaris
      lumbricoides infection may, therefore, cause high-grade fever after cardiac
      surgery.

PMID- 22644819
TI  - Case report and literature review: surgical treatment of a right atrial
      metastatic melanoma from a previously resected "advanced" primary site with
      regional lymph nodes involvement.
AB  - Although melanoma of the right atrium is a rare cardiac tumor, melanoma in
      general has a high propensity to involve the heart. Unfortunately, however, when
      the tumor is involving the heart, widespread metastasis ensues and hence surgery
      becomes a questionable option. We report a case of a young female who presented
      with an advanced skin primary melanoma and regional lymph node involvement and a
      metastasis into the right atrium. Postoperatively tumor dissemination was
      controlled with adjuvant chemotherapy. A vigorous attempt aiming at tumor
      clearance followed by adjuvant multimodality therapy along with a tumor
      surveillance program may improve survival even in advanced cases.

PMID- 22644820
TI  - Aspergillus endocarditis in a native valve without prior cardiac surgery.
AB  - Aspergillus native valve endocarditis continues to be a lethal disease, even when
      maximal therapeutic options are taken. We describe herein a patient with mitral
      valve endocarditis due to Aspergillus fumigatus following colon cancer and
      invasive pulmonary aspergillosis. Voriconazole was effective in controlling
      pulmonary and cerebral aspergillosis, despite the relative ineffectiveness for
      the vegetation. With the combination of aggressive medical and surgical therapy,
      the patient survived and remains without any evidence of infection 2 years later.

PMID- 22644821
TI  - Reoperation on a Starr-Edwards ball valve without structural deterioration.
AB  - Accurate measurement of pressure gradients on echocardiography across a Starr
      Edwards (SE) ball valve is difficult due to its unique flow pattern. The decision
      of indication for reoperation on the valve requires multifactorical evaluation.
      We report a surgical case with an aortic SE ball valve 43 years after
      implantation. There was no apparent structural deterioration on the ball per se,
      yet, remarkable pannus formation was noted beneath the sewing cuff in the left
      ventricular outflow tract.

PMID- 22644822
TI  - Repeat conduit replacement in the pulmonary position without sternal resplitting
      for the patient with repaired Tetralogy of Fallot and the absent inferior caval
      vein.
AB  - Recently, sternal reentry has been performed with low perioperative mortality and
      morbidity. In some patients, however, there are specific problems leading to life
      threatening events during sternal reentry. A 27-year-old woman with repaired
      Tetralogy of Fallot and the absent inferior caval vein was referred to our
      department for pulmonary conduit replacement. Preoperative computed tomography
      disclosed the dominant right coronary artery and the ascending aorta
      longitudinally running just beneath the midline of the sternum. Therefore, we
      selected bilateral antero-lateral thoracotomy as the alternative approach to
      avoid the injury of these vital organs. The left axillar and right femoral artery
      were used for arterial perfusion sites. Venous drainage could be obtained from
      the left superior caval vein and the isolated hepatic vein via the left antero
      lateral thoracotomy, and the right superior caval vein via the right antero
      lateral thoracotomy. We successfully performed the repeat conduit replacement via
      the right antero-lateral thoracotomy.

PMID- 22644823
TI  - [Hearing impairment and language development].
AB  - A child has the first 4 years of life in which to develop speech. The first 8-10
      months see the ability to distinguish sounds; later comes further linguistic
      ability. A hearing impairment more than 25 dB in the better ear in the speech
      frequencies (500-4 000 Hz) for more than 3 months has clear consequences,
      especially in the first 4 years of life. Therefore early diagnosis and treatment
      with rehabilitation of hearing loss is important for proper speech development.

PMID- 22644824
TI  - Novel role for prepatterned nicotinic acetylcholine receptors during myogenesis.
AB  - INTRODUCTION: Before the nerve contacts the skeletal muscle, the nicotinic
      acetylcholine receptors (nAChRs) form aggregates known as prepatterned clusters.
      We investigated their role in the occurrence of Ca(2+) spikes and twitching
      during myogenesis. METHODS: Cultured mouse myotubes were used as cell models.
      Cells were subjected to a combination of immunostaining, Ca(2+) imaging and
      electrophysiological analysis. RESULTS: A single prepatterned nAChR cluster per
      myotube was generally detected. A correlation between formation of the
      prepatterned clusters and occurrence of Ca(2+) spikes and twitching was observed.
      Increase in size of the prepatterned clusters raised the frequency of Ca(2+)
      spikes and twitching. Blockade of the electrical activity triggered by the
      autocrine activation of prepatterned nAChR induced over-numbered nAChR clusters.
      CONCLUSIONS: Prepatterned nAChR aggregation is required for Ca(2+) spikes and
      twitching of developing myotubes. Moreover, prepatterned nAChR-driven electrical
      activity preserves the distribution of nAChRs, mimicking the effect of synaptic
      activity before innervation.

PMID- 22644825
TI  - Comparative analysis of 2-D versus 3-D ultrasound estimation of the fetal adrenal
      gland volume and prediction of preterm birth.
AB  - OBJECTIVE: We aim to test the hypothesis that two-dimensional (2-D) fetal adrenal
      gland volume (AGV) measurements offer similar volume estimates as volume
      calculations based on 3-D technique. METHODS: Fetal AGV was estimated by three
      dimensional (3-D) ultrasound (VOCAL) in 93 women with signs/symptoms of preterm
      labor and 73 controls. Fetal AGV was calculated using an ellipsoid formula
      derived from 2-D measurements of the same blocks (0.523 * length * width *
      depth). Comparisons were performed by intraclass correlation coefficient (ICC),
      coefficient of repeatability, and Bland-Altman method. The corrected AGV (cAGV;
      AGV/fetal weight) was calculated for both methods and compared for prediction of
      preterm birth (PTB) within 7 days. RESULTS: Among 168 volumes, there was a
      significant correlation between 3-D and 2-D methods (ICC = 0.979; 95% confidence
      interval [CI]: 0.971 to 0.984). The coefficient of repeatability for the 3-D was
      superior to the 2-D method (intraobserver 3-D: 30.8, 2-D:57.6; interobserver 3
      D:12.2, 2-D: 15.6). Based on 2-D calculations, cAGV >= 433 mm3/kg was best for
      prediction of PTB (sensitivity: 75%, 95% CI = 59 to 87; specificity: 89%, 95% CI
      = 82 to 94). Sensitivity and specificity for the 3-D cAGV (cutoff >= 420 mm3/kg)
      was 85% (95% CI = 70 to 94) and 95% (95% CI = 90 to 98), respectively. In
      receiver-operating-curve curve analysis, 3-D cAGV was superior to 2-D cAGV for
      prediction of PTB (z = 1.99, p = 0.047). CONCLUSION: 2-D volume estimation of
      fetal adrenal gland using ellipsoid formula cannot replace 3-D AGV calculations
      for prediction of PTB.

PMID- 22644828
TI  - Infants weighing <1500 g: better born too small or too soon?
AB  - OBJECTIVE: To evaluate the influence of intrauterine growth on intact
      neurological outcome at 12 to 24 months in a cohort of infants weighing <1500 g
      at birth. STUDY DESIGN: This retrospective study was conducted in the Department
      of Obstetrics and Gynecology, University of Milano-Bicocca, San Gerardo Hospital,
      Monza, Italy. Perinatal variables were correlated with occurrence of composite
      adverse outcome, including neonatal death or adverse neurodevelopmental outcome
      (ANDO), at 12 to 24 months' follow-up, in 240 consecutive very low-birth-weight
      (VLBW) neonates prenatally classified as growth restricted (IUGR; n = 100) or
      appropriate for gestational age (n = 140). RESULTS: Among the 214 surviving
      neonates, neurological follow-up was available in 163. ANDO was present in 46
      children (28%). At multivariate analysis, only gestational age at delivery was
      independently related to the composite outcome (p < 0.001, odds ratio = 0.69, 95%
      confidence interval 0.59, 0.81), whereas diagnosis of IUGR was not. CONCLUSION:
      Only gestational age at delivery was significantly associated with composite
      adverse outcome in VLBW preterm infants.

PMID- 22644827
TI  - Cytokine and chemokine alterations in Down syndrome.
AB  - OBJECTIVE: Down syndrome (DS) is the leading genetic cause of intellectual
      disability, affecting ~1/800 newborns. Previously we have shown alterations in N
      methyl-D-aspartic acid (NMDA) receptors and neuropeptides (activity-dependant
      neuroprotective protein, glia fibrillary acidic protein) in a murine model of DS.
      Cytokines and chemokines have neuromodulatory and neurotransmitter roles and
      interact with the NMDA receptors. The objective of this study was to evaluate if
      cytokines and chemokines in the hippocampus and cerebellum are altered in this
      model. STUDY DESIGN: We used 8- to 10-month-old animals from the well
      characterized mouse model of DS (Ts65Dn). Learning and memory were assessed in
      the Morris water maze with the Ts65Dn animals demonstrating a learning deficit.
      After completion of the behavioral testing, the brains were removed and the
      hippocampus and cerebellum were separated by microdissection. A panel of
      cytokines, chemokines, and fractalkine were measured in the protein lysates using
      a microsphere-based multiplex immunoassay (Luminex xMAP, Millipore) and
      normalized to total protein concentration. Statistical analysis included the
      nonparametric Mann-Whitney U for the cytokine, chemokine, and fractalkine levels;
      p < 0.05 was considered significant. RESULTS: Levels (median [range]) of
      interleukin (IL)-1beta (6.95 [0.11 to 43.5] versus 14.2 [0.2 to 36.8] pg/mL);
      granulocyte-macrophage colony-stimulating factor (GM-CSF; 3.97 [0.19 to 19.6]
      versus 19.2 [0.2 to 31.1] pg/mL), and macrophage inflammatory protein (MIP)
      1alpha (20.3 [0.11 to 73.3] versus 37.0 [0.22 to 102.7] pg/mL) in the hippocampus
      from Ts65Dn were significantly lower compared with the euploid (control) animals.
      Many cytokines and chemokines were not detected in the hippocampus or cerebellum,
      and others were detectable but not different between the groups. CONCLUSION: We
      found a decreased in GM-CSF, IL-1beta, and MIP-1alpha in the hippocampus of DS
      pups. All three have known interactions with NMDA receptors and their decline may
      explain, in part, the learning deficits associated with DS.

PMID- 22644826
TI  - Relationship between fetal station and successful vaginal delivery in nulliparous
      women.
AB  - OBJECTIVE: To study the relationship between fetal station and successful vaginal
      delivery in nulliparous women. STUDY DESIGN: This was a secondary analysis from a
      previously reported trial of pulse oximetry. Vaginal delivery rates were
      evaluated and compared with respect to the fetal station. Spontaneous labor and
      induction of labor groups were evaluated separately. Multivariable logistic
      regression analysis was performed to adjust for confounding factors. RESULTS:
      Successful vaginal delivery was more frequent with an engaged vertex for
      spontaneous labor (86.2% versus 78.6%; p = 0.01) and induced labor (87.7% versus
      66.1%; p < 0.01). After adjustment, engaged fetal vertex was not associated with
      vaginal delivery for spontaneous labor (odds ratio [OR] 1.5; 95% confidence
      interval [CI] 0.95 to 2.3; p = 0.08) or for women with induced labor (OR 2.2; 95%
      CI 0.96 to 5.1; p = 0.06). CONCLUSION: Among nulliparous women enrolled in the
      FOX randomized trial in spontaneous labor or for labor induction, an engaged
      fetal vertex does not affect their vaginal delivery rate.

PMID- 22644829
TI  - The effect of maternal obesity on pregnancy outcomes of women with gestational
      diabetes controlled with diet only, glyburide, or insulin.
AB  - OBJECTIVE: To examine the effect of obesity on maternal and neonatal outcomes in
      women diagnosed with gestational diabetes mellitus (GDM) and managed with diet
      only, glyburide, or insulin. STUDY DESIGN: Women with singleton gestations
      enrolled for outpatient services diagnosed with GDM and without history of
      pregnancy-related hypertension at enrollment or in a prior pregnancy were
      identified in a database. Women with GDM controlled by diet only (n = 3918),
      glyburide (n = 873), or insulin without prior exposure to oral hypoglycemic
      agents (n = 2229) were included. Pregnancy outcomes were compared for obese
      versus nonobese women within each treatment group and also compared across
      treatment groups within the obese and nonobese populations. RESULTS: Within each
      treatment group, obesity was associated with higher rates of cesarean delivery,
      pregnancy-related hypertension, macrosomia, and hyperbilirubinemia (all p <
      0.05). Higher rates of pregnancy-related hypertension and hyperbilirubinemia were
      observed in women receiving glyburide. CONCLUSION: Obesity adversely affects
      pregnancy outcome in women with GDM. Higher rates of pregnancy-related
      hypertension and hyperbilirubinemia were observed in pregnant women receiving
      glyburide.

PMID- 22644830
TI  - An analysis of second-stage labor beyond 3 hours in nulliparous women.
AB  - OBJECTIVE: To analyze outcomes after second-stage labor beyond 3 hours and
      determine if prolonged second stages were intentional. STUDY DESIGN:
      Retrospective cohort analysis of maternal and neonatal outcomes in nulliparous
      women based on second-stage duration. Medical records were reviewed for
      management decisions in women with second stages >=4 hours; all other outcomes
      were accessed via computerized obstetric database. RESULTS: Second stage
      exceeding 3 hours occurred in 1489 (7%) of 21,991 pregnancies analyzed. Of the
      427 (2%) with second stages >=4 hours, 315 (74%) reached 4 hours unintentionally,
      after a decision for operative delivery had been made. Only 34 (8%) women were
      intentionally allowed to continue second-stage labor beyond 4 hours, and half of
      these ultimately required cesarean. Indices of maternal and neonatal morbidity
      were significantly increased when second stages exceeded 3 hours. CONCLUSION:
      Most second stages reaching 4 hours are unintentional, occurring while awaiting
      an previously decided upon operative delivery. Maternal and neonatal morbidities
      are significantly increased with second stages beyond 3 hours.

PMID- 22644831
TI  - In vitro myometrial contractility profiles of different pharmacological agents
      used for induction of labor.
AB  - OBJECTIVE: To investigate the effects of different pharmacological induction
      agents on myometrial contractility. STUDY DESIGN: Myometrial biopsies were
      obtained from 13 term nonlaboring women undergoing scheduled cesarean delivery.
      Tissue strips were suspended in organ chambers for isometric tension recording.
      The effects of cumulative doses (10-10 mol/L to 10-5 mol/L) of prostaglandin E1
      (PGE1), E2 (PGE2), and oxytocin on spontaneous uterine contractility were
      determined. Areas under the contraction curve were compared using one-way
      analysis of variance on ranks with Dunn post hoc test. RESULTS: Oxytocin-induced
      myometrial contractility was superior to PGE1, PGE2, and time controls (CTR) at
      all the concentrations tested. When only prostaglandins were compared with CTR,
      PGE1 10-5 mol/L increased myometrial contractility, and PGE2 had no effects.
      CONCLUSION: Oxytocin and prostaglandins have different effects on myometrial
      contractility accounting for different mechanisms of action and side effects. The
      increased uterine contractility observed with PGE1 as compared with PGE2 can
      contribute to explain the higher success of vaginal delivery.

PMID- 22644833
TI  - Hypoxia modulation of peroxisome proliferator-activated receptors (PPARs) in
      human glioblastoma stem cells. Implications for therapy.
AB  - Gliobastoma (GB), the most common adult brain tumor, infiltrates normal brain
      area rendering impossible the complete surgical resection, resulting in a poor
      median survival (14-15 months), despite the aggressive multimodality treatments
      post-surgery, such as radiation and chemo-therapy. GB is characterized by hypoxic
      and necrotic regions due to a poorly organized tumor vascularization, leading to
      inadequate blood supply and consequently to hypoxic and necrotic areas. We have
      previously shown that, under hypoxia GB primary cells increased the expression of
      stemness markers as well as the expression of the nuclear receptor peroxisome
      proliferator-activated receptor alpha (PPARalpha) and also the crucial role
      played by PPARs in mouse neural stem cells maintenance and differentiation. Due
      to the importance of lipid signaling in cell proliferation and differentiation,
      in this work, we analyzed the expression of PPARs in GB neurospheres both in
      normoxic and hypoxic conditions. The results obtained suggest a differential
      regulation of the three PPARs by hypoxia, thus indicating a possible therapeutic
      strategy to counteract GB recurrencies.

PMID- 22644832
TI  - Neonatal death in low- to middle-income countries: a global network study.
AB  - OBJECTIVE: To determine population-based neonatal mortality rates in low- and
      middle-income countries and to examine gestational age, birth weight, and timing
      of death to assess the potentially preventable neonatal deaths. METHODS: A
      prospective observational study was conducted in communities in five low-income
      countries (Kenya, Zambia, Guatemala, India, and Pakistan) and one middle-income
      country (Argentina). Over a 2-year period, all pregnant women in the study
      communities were enrolled by trained study staff and their infants followed to 28
      days of age. RESULTS: Between October 2009 and March 2011, 153,728 babies were
      delivered and followed through day 28. Neonatal death rates ranged from 41 per
      1000 births in Pakistan to 8 per 1000 in Argentina; 54% of the neonatal deaths
      were >37 weeks and 46% weighed 2500 g or more. Half the deaths occurred within 24
      hours of delivery. CONCLUSION: In our population-based low- and middle-income
      country registries, the majority of neonatal deaths occurred in babies >37 weeks'
      gestation and almost half weighed at least 2500 g. Most deaths occurred shortly
      after birth. With access to better medical care and hospitalization, especially
      in the intrapartum and early neonatal period, many of these neonatal deaths might
      be prevented.

PMID- 22644834
TI  - Moving beyond response criteria: new measures of success in the treatment of
      sarcomas.
AB  - There is an urgent need to develop new therapies for soft tissue sarcomas.
      Traditional cytotoxic therapies, such as doxorubicin and ifosfamide, have been
      the standard approach to this disease. However, newer paradigms are emerging that
      are less toxic while targeting dysregulated pathways, tumor hypoxia, and genetic
      translocations. These newer therapies require different measures of activity as
      standard response criteria may inaccurately measure their effectiveness. Serious
      consideration of select endpoints and measures of tumor response are crucial to
      make significant strides in the treatment of sarcomas. Current studies on soft
      tissue sarcomas are slowly abandoning response rates while employing progression
      free survival and time to progression as improved endpoints. With time and data,
      our understanding of the relative activity of these agents will grow and lead to
      improved benefits for our patients.

PMID- 22644835
TI  - Increase in serum pregnancy-associated plasma protein-A is correlated with
      increase in cardiovascular risk factors in adult patients with growth hormone
      deficiency.
AB  - Adult Growth Hormone Deficiency (AGHD) is correlated to many adverse effects on
      metabolism and increased cardiovascular risk. Pregnancy-associated plasma protein
      A (PAPP-A) is a protease that promotes IGF-I availability in vascular tissues in
      recent study, and PAPP-A levels have been proposed as an early predictor of
      cardiac events. The aim of our study was to compare PAPP-A levels in AGHD
      patients with that of healthy adult subjects to determine if there is a
      relationship between serum PAPP-A and glucose and lipid metabolism. Twenty AGHD
      patients and 20 healthy, age-matched and weight-matched persons were chosen for
      the study. Their weight, height, blood pressure, body mass index (BMI), body fat
      percentage, waist and hip circumference, and waist-hips ratio were assessed. An
      oral glucose tolerance test was performed and venous blood was collected from the
      each patient's cubital vein for biochemical analysis. Serum PAPP-A level in AGHD
      patients was significantly higher than that of the control group [(7.62 +/- 1.62
      vs. 6.54 +/- 1.31) p < 0.05], and PAPP-A was positively correlated to age, BMI,
      waist circumference and so on. After adjusting for the waist circumference, waist
      hip ratio, 2 h postprandial blood glucose, triglycerides, the serum PAPP-A in
      AGHD patients was positively correlated to the BMI (r = 0.728, p < 0.05) and
      fasting insulin (r = 0.433, p < 0.05). In a multiple step-wise regression
      analysis, BMI, 2 h postprandial glucose, fasting insulin, HOMA-IR were
      independently associated with serum PAPP-A in AGHD patients. The increase in
      serum PAPP-A levels is associated with abnormal glucose metabolism and increased
      risk of atherosclerosis in AGHD patients.

PMID- 22644836
TI  - Insulin resistance is not necessarily an essential element of metabolic syndrome.
AB  - Type 2 diabetes is frequently associated with metabolic syndrome (MetS). Insulin
      resistance (IR) is thought to be the underlying pathophysiology of MetS. The
      purpose of this study is to examine the association of MetS with IR and beta cell
      function. This is a cross-sectional study in NHANES 1999-2000 participants who
      were at least 18 years old, including 911 non-Hispanic whites (NHW), 398 non
      Hispanic blacks (NHB), and 595 Mexican-Americans (MA). MetS was defined based on
      the revised ATP III. IR and beta cell function were calculated using homeostasis
      model assessment (HOMA-IR and HOMA-B). The high-risk tertile was defined as the
      highest HOMA-IR and lowest HOMA-B. The odds ratio (OR) was calculated against the
      other two tertiles. The relationship of HOAM-IR and HOMA-B with the components of
      MetS was also examined. IR was a risk factor of MetS in all three ethnic groups
      (OR 4.17-12.01, P < 0.0001). Fasting glucose, triglycerides, and HDL cholesterol
      were associated with IR (P < 0.001) and correlated with HOMA-IR (P < 0.001),
      while inconsistent results were noted in blood pressure and waist circumference
      among three racial/ethnic groups. However, in the MetS subjects, 32 % of NHW, 28
      % of NHB, and 44 % of MA were not in the IR tertile and in the IR subjects, 25 %
      of NHW, 36 % NHB, and 30 % of MA did not have MetS. No relationship was found
      between beta cell function and MetS. Although IR is a risk factor for MetS, IR is
      neither necessary nor required for MetS.

PMID- 22644839
TI  - Practical evaluation of late-night salivary cortisol: a real-life approach.

PMID- 22644837
TI  - The incidence and prevalence of thyroid autoimmunity.
AB  - The thyroid gland is the most common organ affected by autoimmune disease. Other
      autoimmune diseases, most notably type 1 diabetes mellitus, are increasing in
      incidence. It is unknown whether autoimmune thyroid diseases are following the
      same pattern. This review summarizes studies of autoimmune thyroid disease
      incidence and prevalence since 1950, not only for these measures of occurrences,
      but also for commenting on identified risk factors for thyroid autoimmunity. We
      find that incidence of autoimmune thyroid disease is currently higher than in
      historic series although the studies are so variable in design, patient
      population, disease definition, and laboratory methods that it is impossible to
      tell whether this difference is real. Further research is required to assess the
      possibility of changing disease patterns of autoimmune thyroid disease as opposed
      to simple changes in diagnostic thresholds.

PMID- 22644838
TI  - Mutations in the AVPR2, AVP-NPII, and AQP2 genes in Turkish patients with
      diabetes insipidus.
AB  - The aim of this study was to identify mutations in three different genes, the
      arginine-vasopressin-neurophysin II (AVP-NPII) gene, the arginine-vasopressin
      receptor 2 (AVPR2) gene, and the vasopressin-sensitive water channel aquaporin-2
      (AQP2) gene in Turkish patients affected by central diabetes insipidus or
      nephrogenic diabetes insipidus. This study included 15 patients from unrelated
      families. Prospective clinical data were collected for all patients including the
      patients underwent a water deprivation-desmopressin test. The coding regions of
      the AVPR2, AQP2, and AVP-NPII genes were amplified by polymerase chain reaction
      and submitted to direct sequence analysis. Of the 15 patients with diabetes
      insipidus referred to Gulhane Military Medical Academy, Department of
      Endocrinology and Metabolism, eight patients have AVPR2 mutations, five patients
      have AQP2 mutations and two patients have AVP-NPII mutations. Of the patients,
      which have AVPR2 mutations, one is compound heterozygous for AVPR2 gene. Seven of
      these mutations are novel. Comparison of the clinical outcomes of these mutations
      may facilitate in understanding the functions of AVP-NPII, AQP2, and AVPR2 genes
      in future studies.

PMID- 22644840
TI  - Chronic autoimmune thyroiditis in industrial areas in Brazil: a 15-year survey.
AB  - PURPOSE: To investigate whether there is an increased incidence of chronic
      autoimmune thyroiditis (CAT) in individuals living in the vicinity of industrial
      plants that manufacture petroleum byproducts in the state of Sao Paulo, Brazil.
      METHODS: Between 1989 and 2004, 6,306 patients of both sexes, from 5 to 78 years
      old were divided in two groups according to their home location: Group 1: 3,356
      residents living near industrial plants that manufacture petroleum byproducts
      (Region A), and Group 2: 2,950 residents living far from Region A in an area with
      predominantly steel industries (Region B). For all patients, we measured the
      serum levels of antithyroglobulin antibody, antithyroperoxidase antibody,
      triiodothyronine, thyroxine, free thyroxine and thyrostimulating hormone.
      Sonographic scans of the thyroid gland were also conducted. RESULTS: The
      proportion of patients with CAT coming from Region A increased from 2.5 % (5
      patients with CAT/200 total patients) in 1992 to 57.6 % (106 patients with
      CAT/184 total patients) in 2001. This striking increase was highly significant (p
      < 0.001). Similar findings were not observed in Region B. The difference in the
      number of patients with CAT between 1989 and 2004 coming from Region A and Region
      B was highly significant (p < 0.001), with 905 CAT patients (83.95 %) in Region A
      and 173 CAT patients (16.05 %) in Region B. CONCLUSION: Our results showed a
      striking increase in the incidence of CAT in residents in the vicinity of large
      industrial plants that manufacture petroleum byproducts compared with residents
      living near steel industries, which opens the field to new areas of research.

PMID- 22644841
TI  - Cerebrospinal fluid BAFF and APRIL levels in neuromyelitis optica and multiple
      sclerosis patients during relapse.
AB  - BACKGROUND: BAFF (B-cell activating factor of the tumor necrosis factor family)
      and APRIL (a proliferation-inducing ligand) are two of the major survival factors
      for B cells. Many studies have shown that BAFF levels were elevated in MS
      patients. However, whether the levels of CSF BAFF/APRIL increased in NMO patients
      was still unclear. OBJECTIVE: To measure the CSF BAFF and APRIL concentration of
      in NMO patients, and explore their relationship with disease activity in NMO.
      METHODS: CSF BAFF and APRIL was measured by an enzyme-linked immunosorbent assay
      (ELISA) in NMO (n = 22), MS (n = 18) patients and controls (n = 14). RESULTS:
      Concentration of BAFF and APRIL in NMO patients were significantly higher than MS
      and controls. CSF BAFF and APRIL levels in controls were also lower than MS. Both
      NMO and MS revealed an increased disease disability with increased CSF BAFF. CSF
      APRIL was associated with EDSS scores in NMO, but not found in MS. CONCLUSIONS:
      BAFF/APRIL system considered important for aggressive B cells and T-cell
      responses, and may stimulates B cells and T cell activation in acute relapse of
      NMO and MS. In NMO patients, CSF BAFF and APRIL may be key factors of B cell
      immune response and reflect disease severity.

PMID- 22644842
TI  - A long-acting erythropoietin fused with noncytolytic human Fc for the treatment
      of anemia.
AB  - The Fc fusion technology has been introduced to generate long-acting antagonistic
      drugs such as Enbrel, Orencia and Amevive. Here, Genexine created a novel
      noncytolytic hybrid Fc (hyFc) as a carrier of agonistic protein drugs using
      naturally existing IgD and IgG4 Fcs without any mutation in the hyFc region. The
      erythropoietin (EPO) fused with hyFc exhibited little binding activity to
      FcgammaR and C1q molecules that are main mediators for death of target cells. The
      EPO-hyFc showed higher in vitro and in vivo bioactivities than EPOIgG1 Fc and
      highly glycosylated EPO (Aranesp). Phase I clinical trial with EPO-hyFc is
      currently undergoing in Korea.

PMID- 22644843
TI  - A flavonol triglycoside and investigation of the antioxidant and cell stimulating
      activities of Annona muricata Linn.
AB  - Chemical investigation on leaves of Annona muricata resulted in the isolation of
      the flavonol triglycoside, quercetin 3-O-alpha-rhamnosyl-(1"" -> 6")-beta
      sophoroside, together with twelve known phenolics. The structures of these
      compounds were established by 1D- and 2D-nuclear magnetic resonance spectroscopic
      techniques and mass spectrometry data. The in vitro antioxidant studies of the
      investigated aqueous ethanol extract and its column fractions were accomplished
      using the oxygen radical absorbance capacity (ORAC) method. A stimulating effect
      on HaCaT human keratinocytes by the leaf extract was also assessed. Il-6
      production after UV irradiation was not influenced by A. muricata leaf extract.

PMID- 22644844
TI  - Synthesis and anticancer activity of 5,6,8,13-tetrahydro-7H-naphtho[2,3-a][3]
      benzazepine-8,13-diones.
AB  - A series of naphthoquinones fused benzazepines, 5,6,8,13-tetrahydro-7H
      naphtho[2,3-a][3]-benzazepine-8,13-diones, were synthesized and evaluated for
      their anticancer activity against four cell lines; human breast carcinoma cell
      line, human cervix carcinoma cell line, human hepatocellular carcinoma cell line
      and human keratinocyte cell line. The results showed that 5,6,8,13-tetrahydro
      2,3,4,9-tetramethoxy-7H-naphtho[2,3-a][3]benzazepine-8,13-dione 4g and 5,6,8,13
      tetrahydro-2,3,9-trimethoxy-7H-naphtho[2,3-a][3]benzazepine-8,13-dione 4h have
      significant cytotoxicity against a hepatocellular carcinoma cell line with IC(50)
      = 3.5 MUg/mL and 3.0 MUg/mL, respectively.

PMID- 22644845
TI  - Bioactive cadinane-type compounds from the soft coral Sinularia scabra.
AB  - Two new cadinane-type sesquiterpenoids, scabralins A (1) and B (2) were obtained
      from the soft coral Sinularia scabra. Metabolite 1 was shown to exhibit moderate
      to weak cytotoxicity against MCF-7, WiDr, Daoy, and HEp 2 cancer cell lines.
      Also, incubation with 10 uM compound 1 significantly inhibited the accumulation
      of the pro-inflammatory inducible nitric oxide synthase protein in
      lipopolysaccharide-stimulated RAW264.7 macrophage cells.

PMID- 22644846
TI  - New topoisomerases inhibitors: synthesis of rutaecarpine derivatives and their
      inhibitory activity against topoisomerases.
AB  - A series of rutaecarpine derivatives were prepared by employing previously
      reported methods and their inhibitory activities against topoisomerase I and II
      were evaluated. Among them, strongly cytotoxic 10-bromorutaecarpine and 3
      chlororutaecarpine showed strong inhibitory activities against topo I and II.

PMID- 22644847
TI  - Anticancer activity of undecapeptide analogues derived from antimicrobial
      peptide, brevinin-1EMa.
AB  - In spite of great advances in cancer therapy, cancer remains the major cause of
      death throughout the world. The increasing resistance of cancer cells towards
      current anticancer drugs requires development of anticancer agents with a new
      mode of action. Some antimicrobial peptides have become therapeutic candidates as
      new anticancer agents. As part of an effort to develop new antimicrobial and/or
      anticancer agents from natural peptides with low molecular weights, we have
      investigated the shortest bioactive analogues, which were derived from a 24
      residue antimicrobial peptide, Brevinin-1EMa. Recently, we found four bioactive
      undecapeptides derived from a cationic, amphipathic alpha-helical, 11-residue
      peptide (named herein GA-W2: FLGWLFKWASK-NH(2)) (Won et al., 2011). In order to
      identify the potential of these peptides as anticancer agents, we investigated
      the anticancer activity of four undecapeptides against seven tumor cell lines
      such as A498 (kidney), A549 (lung), HCT116 (colon), MKN45 (stomach), PC-3
      (prostate), SK-MEL-2 (skin) and SK-OV-3 (ovary). GA-K4 (FLKWLFKWAKK-NH(2)), which
      had the most potent antimicrobial activity of the four undecapeptides, also
      exhibited the most potent anticancer activity and synergistic effect in
      combination with doxorubicin. Therefore, GA-K4 peptide may be a potentially
      useful candidate as an anticancer peptide agent.

PMID- 22644848
TI  - Bioassay-guided isolation of novel compound from Paeonia suffruticosa Andrews
      roots as an IL-1beta inhibitor.
AB  - The inhibition of Interleukin-1beta (IL-1beta) is of substantial interest for the
      treatment of rheumatoid arthritis. Using an in vitro assay with RAW 264.7 cells,
      oxo-acetic acid 2-ethoxy-4-(3-hydroxy-2-oxopropyl) phenyl ester (1) was isolated
      from the roots of Paeonia suffruticosa Andrews as an inhibitor of IL-1beta with
      an IC(50) value of 56 MUM. Compound 1 is a novel phenylesteric compound from P.
      suffruticosa Andrews. Compound 1 was shown to inhibit the production of pro
      inflammatory cytokines in RAW 264.7 cells. Thus, a possible new action of novel
      compound is provided explaining the anti-rheumatoid arthritic properties of P.
      suffruticosa Andrews.

PMID- 22644849
TI  - Synthesis of novel pyrazole and dihydropyrazoles derivatives as potential anti
      inflammatory and analgesic agents.
AB  - Novel dihydropyrazole 5-8, 10 and pyrazole derivatives 12, 14, 15, 17 were
      synthesized. The structures of the newly synthesized compounds were elucidated by
      spectral and elemental analyses. The anti-inflammatory activity of all new
      compounds was evaluated using the carrageenan-induced rat paw edema test using
      indomethacin and celecoxib as reference drugs. The most active derivatives as
      anti-inflammatory agents were accordingly tested for their analgesic activity
      using the p-benzoquinone-induced writhing method in mice and results revealed
      that these compounds had also good analgesic activity. The ulcerogenic liability
      of the selected compounds was also evaluated. Results showed that the selected
      derivatives had anti-inflammatory activity comparable to or slightly lower than
      the reference drugs, reaching about 82% inhibition with a considerable gastric
      safety profile.

PMID- 22644850
TI  - Anti-inflammatory and antioxidant activities of constituents isolated from
      Pueraria lobata roots.
AB  - In order to evaluate the anti-inflammatory and antioxidant activities of Pueraria
      lobata roots and its active components, in vitro inhibitory activities against
      lipopolysaccharide (LPS)-induced nitric oxide (NO) production, inducible nitric
      oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein expression, and tert
      butylhydroperoxide (t-BHP)-induced reactive oxygen species (ROS) generation in
      RAW 264.7 cells, as well as in vitro scavenging activities against 1,1-diphenyl-2
      picrylhydrazyl (DPPH), peroxynitrite (ONOO(-)), nitric oxide (NO.), superoxide
      anion (.O(2)(-)) and total ROS, and inhibitory activities against ONOO(-)
      mediated tyrosine nitration, were determined. Repeated column chromatography was
      performed to isolate four known compounds from the anti-inflammatory and
      antioxidant EtOAc fraction: daidzein; genistein; puerarin; (+)-puerarol B-2-O
      glucopyranoside; four known compounds from the anti-inflammatory n-hexane
      fraction: lupenone; lupeol; puerarol; coumestrol; seven known compounds from the
      antioxidant n-BuOH fraction: allantoin; 3'-hydroxypuerarin; daidzein 8-C-apiosyl
      (1->6)-glucoside; puerarin; genistin; 3'-methoxypuerarin; daidzin. Among these
      compounds, lupenone and lupeol reduced NO production, as well as iNOS and COX-2
      protein levels in LPS-stimulated RAW 264.7 cells. Furthermore, lupeol showed
      significant inhibitory activity against intracellular ROS generation by t-BHP.
      Meanwhile, 3'-hydroxypuerarin showed marked ONOO(-), NO., total ROS scavenging
      activities, and weak .O(2)(-) scavenging activity, while 3'-methoxypuerarin
      showed ONOO(-) scavenging activity and weak NO. and O(2)(-) scavenging
      activities, suggesting that existence of the 3'-hydroxyl group in puerarin plays
      an important role in the scavenging of ONOO(-), NO., and total ROS, as well as
      inhibiting the ONOO(-)-mediated tyrosine nitration mechanism. These results
      indicate that P. lobata roots and its constituents may be a useful therapeutic
      and preventive approach to various inflammatory diseases and oxidative stress
      related disease.

PMID- 22644851
TI  - Preparation and characterization of a novel pH-sensitive coated microsphere for
      duodenum-specific drug delivery.
AB  - The aim of this study is to develop a duodenum-specific drug delivery system on
      the basis of a pH-sensitive coating and a mucoadhesive inner core for eradication
      of Helicobacter pylori (H. pylori) in the ulcer duodenum. Hydroxypropyl
      methylcellulose acetate maleate (HPMCAM) was used as the pH-sensitive material,
      which dissolves around pH 3.0. The mucoadhesive microspheres loaded with
      furazolidone (FZD-ad-MS) were prepared by the emulsification-solvent evaporation
      method using Carbopol 971NP as the mucoadhesive polymer. The prepared pH
      sensitive coated mucoadhesive microspheres (AM-coated-MS) were characterized in
      regards to particle size, drug loading efficiency, morphological change, drug
      stability, drug release and in vitro anti-H. pylori activity. The particle size
      was 160.97 +/- 47.24 MUm and 336.44 +/- 129.34 MUm, and the drug content was
      42.33 +/- 3.43% and 10.96 +/- 1.29% for FZD-ad-MS and AM-coated-MS, respectively.
      The morphological changes in different pH media were characterized by scanning
      electron microscopy (SEM). HPMCAM coating improved the stability of the FZD-ad-MS
      and these particles were expected to remain intact until their arrival in the
      duodenum. The drug release was extremely suppressed at pH 1.2 for AM-coated-MS,
      but increased at pH 4.0 after regeneration of FZD-ad-MS. In addition, FZD-ad-MS
      exhibited excellent anti-H. pylori activity in vitro. Thus, the HPMCAM-coated
      microspheres developed in this study hold great promise for use as a duodenum
      specific drug delivery system for H. pylori clearance.

PMID- 22644852
TI  - Localized delivery of cisplatin for the effective management of squamous cell
      carcinoma from protransfersome formulation.
AB  - The present study is designed to investigate the local delivery of Cisplatin in
      cutaneous epithelial malignancies from protransfersome. Cisplatin-loaded
      protransfersome was prepared and characterized for size, zeta potential, surface
      morphology, percentage drug entrapment, in vitro drug permeation, vesicle-skin
      interaction, drug-excipients interaction, and stability study. An in vivo study
      was also performed to evaluate the efficacy of the proposed system. The size of
      the system was found to be 1115.56 +/- 254 nm with zeta potential of -61.1 mV.
      Morphological studies revealed the defined structure of vesicles. The percentage
      entrapment of Cisplatin was found to be 97.97 +/- 1.95% with skin permeation data
      of 560.20 +/- 7.89 MUg/cm(2). The presence of a fluorescence marker in the skin
      showed better skin penetration ability of the protransfersome. On comparison with
      IR spectra, it was clear that there was no significant interaction between the
      encapsulated drug and the excipients. In vivo performance of the system showed an
      increase in the therapeutic efficacy of drug with less systemic toxicity. The
      findings of the work appear to support improved, site-specific, and localized
      drug action, thus providing a better option to deal with skin-cited problems like
      squamous cell carcinoma. Further, the ultra-deformable nature of system seems to
      permit better delivery of the drug at the tumor site.

PMID- 22644853
TI  - Solid state of a new PDE-5 inhibitor DA-8159: characterization, dissolution,
      transformation.
AB  - The polymorphic forms of a new PDE-5 inhibitor DA-8159 were prepared and
      characterized by differential scanning calorimetry (DSC), powder X-ray
      diffractometry (PXRD) and thermogravimetric analysis (TG). Two crystal forms and
      one amorphous form of DA-8159 have been isolated by recrystallization and
      characterized by DSC, TG and PXRD. From the TG data it was confirmed that two
      crystal forms are neither solvates nor hydrates. The PXRD patterns of the two
      crystal forms were different. In the dissolution studies in simulated intestinal
      fluid at 37 +/- 0.5 degrees C, the solubility decreased in the order of amorphous
      form > Form 1 > Form 2. After storage of 60 days, Form 1 was transformed to Form
      2. Form 2 was not transformed. The amorphous form was transformed to Form 2 at
      52% R.H. and 95% R.H., but it did not transform at 0% R.H.

PMID- 22644854
TI  - Cell growth inhibition and induction of apoptosis by snake venom toxin in ovarian
      cancer cell via inactivation of nuclear factor kappaB and signal transducer and
      activator of transcription 3.
AB  - Snake venom toxin from Vipera lebetina turanica induces apoptosis in many cancer
      cell lines, but there is no study about the apoptotic effect of snake venom toxin
      on human ovarian cancer cells. In this study, we investigated the apoptotic
      effect of snake venom toxin in human ovarian cancer PA-1 and SK-OV3 cells. Snake
      venom toxin dose dependently (0~10 MUg/mL) inhibited ovarian cancer cell growth
      with IC(50) values 4.5 MUg/mL in PA-1 cells, and 6.5 MUg/mL in SK-OV3 cells. Our
      results also showed that apoptotic cell death increased by snake venom toxin in a
      dose dependent manner (0~10 MUg/mL). Consistent with increased cell death, snake
      venom toxin increased the expression of pro-apoptotic protein Bax and caspase-3,
      but down-regulated anti-apoptotic protein Bcl-2. Untreated ovarian cancer cells
      showed a high DNA binding activity of nuclear factor B (NF-kappaB), but it was
      inhibited by snake venom toxin accompanied by inhibition of p50 and p65
      translocation into the nucleus as well as phosphorylation of inhibitory kappaB.
      Snake venom toxin also inhibited DNA binding activity of the signal transducer
      and activator of transcription 3 (STAT3). Moreover, the combination treatment of
      NF-kappaB (salicylic acid, 1 or 5 MUM) and STAT3 (stattic, 1 MUM) with snake
      venom toxin (1 MUg/mL) further enhanced cell growth inhibitory effects of snake
      venom toxin. These results showed that snake venom toxin from Vipera lebetina
      turanica caused apoptotic cell death of ovarian cancer cells through the
      inhibition of NF-kappaB and STAT3 signal, and suggested that snake venom toxin
      may be applicable as an anticancer agent for ovarian cancer.

PMID- 22644855
TI  - Attenuation of aortic injury by ursolic acid through RAGE-Nox-NFkappaB pathway in
      streptozocin-induced diabetic rats.
AB  - Vascular complications are the leading causes of morbidity and mortality in
      diabetes mellitus (DM). The RAGE (receptor for advanced glycation end products)
      NADPH oxidase-NF-kappaB signal transduction pathway plays an important role in
      the development of oxidative stress-related vascular complications in DM. Ursolic
      acid (UA), a pentacyclic triterpenoid derived from plants, has been reported to
      have multiple pharmacological effects, including a potent antioxidant activity.
      This study aimed to investigate both the effect of UA on aortic injury in
      streptozotocin (STZ)-induced diabetic rats and the drug's mechanism of action.
      STZ-induced diabetic animals were randomized in one of the following 4 groups: no
      treatment (diabetic model group), aminoguanidine (AG, 100 mg/kg), high-dose UA
      (50 mg/kg), and low-dose UA (25 mg/kg). A non-diabetic control group was followed
      concurrently. After 8 weeks, the diabetic model rats exhibited: severe aortic
      arch injury, histologically elevated serum glucose, fructosamine, and
      glycosylated hemoglobin; and accumulation of advanced glycation end products
      (AGEs) in the arota. In addition, the levels of RAGE protein, transcription
      factor NF-kappaB p65, and the p22phox subunit of NADPH oxidase were increased, as
      were the serum levels of malondialdehyde and tumor necrosis factor-alpha (TNF
      alpha; p < 0.01 vs control), suggesting that the mechanisms of oxidative stress
      contributed to vascular injury in the diabetic model group. In contrast, rats
      treated with UA (50 mg/kg) had a markedly less vascular injury and significantly
      improved biochemical parameters. Oxidative balance was also normalized in the UA
      treated rats, and a marked reduction in the levels of RAGE and p22phox paralleled
      the reduced activation of NF-kappaB p65 and TNF-alpha (p < 0.01 and p < 0.05,
      respectively, vs diabetic model). These findings suggest that UA may suppress
      oxidative stress, thus blunting activation of the RAGE-NADPH oxidase-NF-kappaB
      signal transduction pathway, to ameliorate vascular injury in the STZ-induced DM
      rats.

PMID- 22644857
TI  - Inhibitory effects of Glycyrrhizae radix and its active component,
      isoliquiritigenin, on Abeta(25-35)-induced neurotoxicity in cultured rat cortical
      neurons.
AB  - This study investigated an ethanol extract from Glycyrrhizae radix (GR), the root
      of Glycyrrhiza uralensis (Leguminosae), for possible neuroprotective effects on
      neurotoxicity induced by amyloid beta protein (Abeta) (25-35) in cultured rat
      cortical neurons. Exposure of cultured cortical neurons to 10 MUM Abeta (25-35)
      for 36 h induced neuronal apoptotic death. GR (10-50 MUg/mL) prevented the Abeta
      (25-35)-induced neuronal apoptotic death, as assessed by a MTT assay and Hoechst
      33342 staining. Furthermore, GR decreased the expression of Bax and active
      caspase-3, proapoptotic proteins, and increased Bcl-2, an antiapoptotic protein.
      GR also significantly inhibited Abeta (25-35)-induced elevation of the
      intracellular Ca(2+) concentration ([Ca(2+)](i)) and generation of reactive
      oxygen species (ROS) measured by fluorescent dyes. Isoliquiritigenin (1-20 MUM),
      isolated from GR as an active component, inhibited Abeta (25-35)-induced neuronal
      apoptotic death, elevation of [Ca(2+)](i), ROS generation, and the change of
      apoptosis-associated proteins in cultured cortical neurons, suggesting that the
      neuroprotective effect of GR may be, at least partly, attributable to this
      compound. These results suggest that GR and isoliquiritigenin prevent Abeta (25
      35)-induced neuronal apoptotic death by interfering with the increases of
      [Ca(2+)](i) and ROS, and GR may have a possible therapeutic role for preventing
      the progression of neurodegenerative disease such as Alzheimer's disease.

PMID- 22644856
TI  - Chrysophanol-induced necrotic-like cell death through an impaired mitochondrial
      ATP synthesis in Hep3B human liver cancer cells.
AB  - Liver cancer is the most common form of cancer in Taiwan and it usually responds
      to chemotherapy. However, patients often have side effects to the
      chemotherapeutic drugs. Thus new agents are urgently required to treat liver
      cancer. Chrysophanol, one of the anthraquinone derivatives, was reported to
      inhibit some human cancer cell growth which may be due to the induction of
      apoptosis similar to other anthraquinone derivatives though such actions have not
      been reported. In the present study, we reported that chrysophanol inhibits cell
      growth in Hep3B liver cancer cells based on the following observations: 1) induc
      cell morphological changes; 2) decreased percentage of viable cells; 3) induced S
      phase arrest of cell cycle progression; 4) induced DNA damage as measured by
      comet assay and DAPI staining. Chrysophanol-induced cell death however, seems to
      be related to necrotic processes rather than typical apoptosis. Chrysophanol
      induced reactive oxygen species and Ca(2+) production and decreased mitochondrial
      membrane potential (DeltaPsim) and ATP levels in Hep3B cells. No effects were
      observed on known protein regulators of apoptosis such as Bax and Bcl-2.
      Chrysophanol-induced cell death took place independently of caspase-8 and -9.
      Based on our findings, we propose that chrysophanol reduces cellular ATP levels
      causing a drop in energy resulting in necrotic-like cell death.

PMID- 22644858
TI  - Competitive inhibition of cytosolic Ca2+-dependent phospholipase A2 by acteoside
      in RBL-2H3 cells.
AB  - The aim of this study was to investigate whether acteoside isolated from
      Clerodendron trichotomum Thunberg may act as a selective inhibitor of
      phospholipase A(2) in RBL-2H3 cells. Acteoside dose-dependently inhibited 0.5 MUM
      melittin-induced release of [(3)H]arachidonic acid, which was due to the
      inhibition of cytosolic Ca(2+)-dependent phospholipase A(2) (cPLA(2)) rather than
      secretory PLA(2) (sPLA(2)). In Dixon plots, the apparent K ( i ) value of
      acteoside on cPLA(2) was 5.9 MUM and the inhibitory pattern appeared to be a
      competitive inhibitor. The above data, suggests that acteoside acts as a
      competitive inhibitor of cPLA(2) in RBL-2H3 cells.

PMID- 22644860
TI  - Variability of gemcitabine accumulation and its relationship to expression of
      nucleoside transporters in peripheral blood mononuclear cells.
AB  - The concentrative nucleoside transporter CNT1 and equilibrated nucleoside
      transporter ENT1 mediate the cellular uptake of naturally occurring pyrimidine
      and purine nucleosides and many structurally diverse anticancer and antiviral
      nucleoside analogs, thereby regulating drug responses or toxicity at the target
      site. The objectives of this study were to analyze interindividual variations in
      the cellular accumulation of gemcitabine and to examine the correlation between
      the uptake of gemcitabine and expression levels of CNT1 and ENT1 transporters.
      Gemcitabine was a substrate for both CNT1 and ENT1 with higher affinity to CNT1
      than to ENT1. The difference in gemcitabine uptake was 4.8-fold in peripheral
      blood mononuclear cells (PBMCs) from 10 subjects. Among these, the CNT1- and ENT1
      mediated uptake of gemcitabine was 14.3- and 16.5-folds, respectively. CNT1
      mediated gemcitabine uptake showed a higher correlation with the CNT1 expression
      level than did ENT1-mediated uptake with ENT1 expression level. In conclusion,
      CNT1 seemed to be a major contributing factor to gemcitabine uptake in PBMCs and
      showed 14.3-fold inter-individual variations. However, ENT1-mediated uptake of
      gemcitabine might compensate for the total uptake of gemcitabine; therefore, the
      variation in the apparent accumulation of gemcitabine was smaller than that of
      the individual transporters.

PMID- 22644859
TI  - Effects of geranyl-phloroacetophenone on the induction of apoptosis and
      chemosensitization of adriamycin-resistant MCF-7 human breast cancer cells.
AB  - Polyphenols are known to induce apoptosis in many cancer cells and are proposed
      to be promising modulators of drug resistance. In the present study, we report
      that 3-geranyl-phloroacetophenone (3-GAP), a synthetic polyphenol, induces
      apoptosis and modulates drug resistance. In adriamycin-resistant MCF-7 human
      breast cancer (MCF-7/ADR) cells, which express a mutant form of p53, 3-GAP
      induced significant apoptosis, which was accompanied by no change in p53
      transcriptional activity, but an increase in Bax expression, cyt c release, and
      activation of caspase-9, 7, and 3. In addition, 3-GAP significantly decreased the
      activity and expression level of glutathione S-transferase pi (GSTpi), a factor
      that induces drug resistance. Along with GSTpi inhibition, 3-GAP also induced a
      marked depletion of GSH, an endogenous antioxidant. The GST-inhibitory activity
      of 3-GAP correlated with the sensitization of MCF-7/ADR cells to doxorubicin.
      Under serum withdrawal conditions, the JNK inhibitor SP600125 significantly
      decreased the viability of the parent MCF-7 cells but not of MCF-7/ADR cells. In
      addition, the viability of 3-GAP-treated MCF-7/ADR cells was similar to those of
      MCF-7 cells treated with SP600125 alone or MCF-7/ADR cells co-treated with
      SP600125 and 3-GAP. These results indicate that JNK activity in MCF-7/ADR cells
      is halted by high levels of GSTpi, and that 3-GAP releases JNK from GSTpi's
      inhibition. In conclusion, 3-GAP induces apoptosis in and sensitizes drug
      resistant MCF-7/ADR cells. These effects are mediated through p53-independent
      caspase-3 activation and reduction of the capacity for cellular antioxidants,
      such as GSTpi and GSH.

PMID- 22644861
TI  - Suppression of T cell functions by hydroxamic acid-based histone deacetylase
      inhibitors.
AB  - Histone deacetylase inhibitors (HDACis) have recently been shown to suppress
      inflammatory responses at much lower concentrations than that the concentrations
      that produce an antitumor effect. In the current study, the inhibitory activity
      of T cell functions by three different HDACis was compared, and the mechanisms
      underlying the inhibitory activity were demonstrated. Trichostatin-A (TSA) and
      scriptaid (ST) had potent inhibitory effects on the proliferation of T cells. TSA
      suppressed the synthesis of the T cell-activating cytokine, interleukin (IL)-2,
      and the T cell-derived cytokines, interferon (IFN)-gamma, IL-4, and IL-13. In
      addition, TSA induced inhibition of cell cycle progression and IL-2 receptor
      expression. On the whole, TSA had a stronger effect on T cell functions than
      other HDACis. Similarly, a longer duration of hyperacetylation was observed in
      the cells that had been exposed to TSA. Thus, the inhibition of histone
      deacetylation appears to be related to the inhibitory effect of TSA. These
      results are expected to serve as a guide for future studies on the ability of
      HDACis to inhibit acute and chronic inflammatory diseases provoked by T cells.

PMID- 22644862
TI  - The impact of AT1002 on the delivery of ritonavir in the presence of bioadhesive
      polymer, carrageenan.
AB  - New insights into the modification of the tight junctions theoretically offer the
      opportunity to regulate the diffusion barrier and then make it possible to
      investigate a permeation enhancer of low-bioavailability therapeutic agents.
      AT1002, a minimum biologically active fragment of zonula occludens toxin which
      reversibly opens intercellular tight junctions after binding to the Zonulin
      receptor, increased the transport of various molecular weight markers or low
      bioavailability agents. The objective of this study was continuously to evaluate
      the permeation-enhancing ability of AT1002 in the presence of the bioadhesive
      agent, carrageenan after intranasal administration of the antiretroviral drug,
      ritonavir, and the permeation enhancement ratio compared with the previous
      results. The permeation-enhancing effect of AT1002 was significantly promoted by
      the bioadhesive agent, carrageenan. The administration of ritonavir with AT1002
      and carrageenan resulted in a 2.55-fold increase in AUC(0-240min) and a 2.48-fold
      increase in C(max) compared with the control group. However, AT1002 in the
      absence of carrageenan did not produce a statistic enhancement in the absorption
      of ritonavir. Hence, AT1002 together with the addition of carrageenan may open a
      new approach of research in the tight junction modulated permeation enhancer, and
      allow the development of the mucosal drug delivery of therapeutic agents.

PMID- 22644863
TI  - Interleukin-11 increases cell motility and up-regulates intercellular adhesion
      molecule-1 expression in human chondrosarcoma cells.
AB  - Interleukin-11 (IL-11) was originally identified as the cytokine that could
      induce the proliferation of human cells. Recent studies have shown that IL-11
      plays a critical role in tumor growth, angiogenesis, and metastasis.
      Chondrosarcoma is a type of highly malignant tumor with a potent capacity to
      invade locally and cause distant metastasis. However, the effects of IL-11 on
      human chondrosarcoma cells are largely unknown. Here, we found that IL-11
      increased the migration and expression of intercellular adhesion molecule-1
      (ICAM)-1 in human chondrosarcoma cells. We also found that human chondrosarcoma
      tissues had significant expression of the IL-11 which was higher than that in
      primary chondrocytes. The phosphatidylinositol 3-kinase (PI3K), Akt, and NF
      kappaB pathways were activated by IL-11 treatment, and the IL-11-induced
      expression of ICAM-1 and migration activity were inhibited by the specific
      inhibitors and mutant forms of PI3K, Akt, and NF-kappaB cascades. Taken together,
      our results indicate that IL-11 enhanced the migration of the chondrosarcoma
      cells by increasing ICAM-1 expression through the IL-11Ralpha receptor, PI3K,
      Akt, and NF-kappaB signal transduction pathway.

PMID- 22644864
TI  - Does early feeding promote development of oral tolerance?
AB  - The prevalence of food allergy has continued to rise over the last 10-15 years,
      with building concern over the underlying causes and the best strategies to
      reverse this. Although it is still not clear if infant feeding practices play any
      significant role in either the aetiology of this epidemic or in its prevention,
      these have nonetheless been core to many previous prevention strategies. Early
      'allergen avoidance' strategies have not only failed, but have instead been
      increasingly associated with increased risk of allergic disease. Together with
      other observations in humans and animals, this suggests that earlier introduction
      of allergenic foods may be a more logical preventive strategy. Based on this,
      there are several randomised controlled trials world-wide assessing the merits of
      early introduction of complementary feeding and/or allergenic foods. Until the
      results of these studies are available it is difficult to provide definitive
      recommendations regarding the role of early feeding in the induction of oral
      tolerance and prevention of food allergy.

PMID- 22644865
TI  - Non-IgE-mediated gastrointestinal food allergies: distinct differences in
      clinical phenotype between Western countries and Japan.
AB  - Non-IgE-mediated gastrointestinal food allergies, including food-protein-induced
      enterocolitis, enteropathy, proctocolitis and allergic eosinophilic
      gastroenteritis, seem to be increasing in several regions in the world. However,
      unlike the case of IgE-mediated food allergy, development of diagnostic
      laboratory tests and our understanding of the immunological mechanisms involved
      in non-IgE-mediated gastrointestinal food allergies lag. Although the clinical
      entities in Western countries have been well established, the clinical phenotypes
      might differ somewhat among the human races and geographical regions. In Japan,
      non-IgE-mediated gastrointestinal food allergies have increased sharply since the
      late 1990s, and clinicians have sometimes experienced confusion because of
      differences in the clinical phenotypes from those seen in Western countries.
      Aiming to solve this problem, we performed clinical research and determined a
      useful method for dividing patients into four clusters with distinctive clinical
      symptoms. We are confident this method will help in diagnosing and treating these
      patients. We also tried to clarify the differences between these patients in
      Japan and Western countries.

PMID- 22644866
TI  - Role of cockroach proteases in allergic disease.
AB  - Allergic asthma is on the rise in developed countries, and cockroach exposure is
      a major risk factor for the development of asthma. In recent years, a number of
      studies have investigated the importance of allergen-associated proteases in
      modulating allergic airway inflammation. Many of the studies have suggested the
      importance of allergen-associated proteases as having a direct role on airway
      epithelial cells and dendritic cells. In most cases, activation of the protease
      activated receptor (PAR)-2 has been implicated as a mechanism behind the potent
      allergenicity associated with cockroaches. In this review, we focus on recent
      evidence linking cockroach proteases to activation of a variety of cells
      important in allergic airway inflammation and the role of PAR-2 in this process.
      We will highlight recent data exploring the potential mechanisms involved in the
      biological effects of the allergen.

PMID- 22644867
TI  - Semi-automated neuron boundary detection and nonbranching process segmentation in
      electron microscopy images.
AB  - Neuroscientists are developing new imaging techniques and generating large
      volumes of data in an effort to understand the complex structure of the nervous
      system. The complexity and size of this data makes human interpretation a labor
      intensive task. To aid in the analysis, new segmentation techniques for
      identifying neurons in these feature rich datasets are required. This paper
      presents a method for neuron boundary detection and nonbranching process
      segmentation in electron microscopy images and visualizing them in three
      dimensions. It combines both automated segmentation techniques with a graphical
      user interface for correction of mistakes in the automated process. The automated
      process first uses machine learning and image processing techniques to identify
      neuron membranes that deliniate the cells in each two-dimensional section. To
      segment nonbranching processes, the cell regions in each two-dimensional section
      are connected in 3D using correlation of regions between sections. The
      combination of this method with a graphical user interface specially designed for
      this purpose, enables users to quickly segment cellular processes in large
      volumes.

PMID- 22644868
TI  - Development of PowerMap: a software package for statistical power calculation in
      neuroimaging studies.
AB  - Although there are a number of statistical software tools for voxel-based
      massively univariate analysis of neuroimaging data, such as fMRI (functional
      MRI), PET (positron emission tomography), and VBM (voxel-based morphometry), very
      few software tools exist for power and sample size calculation for neuroimaging
      studies. Unlike typical biomedical studies, outcomes from neuroimaging studies
      are 3D images of correlated voxels, requiring a correction for massive multiple
      comparisons. Thus, a specialized power calculation tool is needed for planning
      neuroimaging studies. To facilitate this process, we developed a software tool
      specifically designed for neuroimaging data. The software tool, called PowerMap,
      implements theoretical power calculation algorithms based on non-central random
      field theory. It can also calculate power for statistical analyses with FDR
      (false discovery rate) corrections. This GUI (graphical user interface)-based
      tool enables neuroimaging researchers without advanced knowledge in imaging
      statistics to calculate power and sample size in the form of 3D images. In this
      paper, we provide an overview of the statistical framework behind the PowerMap
      tool. Three worked examples are also provided, a regression analysis, an ANOVA
      (analysis of variance), and a two-sample T-test, in order to demonstrate the
      study planning process with PowerMap. We envision that PowerMap will be a great
      aide for future neuroimaging research.

PMID- 22644869
TI  - Three-dimensional analysis of spiny dendrites using straightening and unrolling
      transforms.
AB  - Current understanding of the synaptic organization of the brain depends to a
      large extent on knowledge about the synaptic inputs to the neurons. Indeed, the
      dendritic surfaces of pyramidal cells (the most common neuron in the cerebral
      cortex) are covered by thin protrusions named dendritic spines. These represent
      the targets of most excitatory synapses in the cerebral cortex and therefore,
      dendritic spines prove critical in learning, memory and cognition. This paper
      presents a new method that facilitates the analysis of the 3D structure of spine
      insertions in dendrites, providing insight on spine distribution patterns. This
      method is based both on the implementation of straightening and unrolling
      transformations to move the analysis process to a planar, unfolded arrangement,
      and on the design of DISPINE, an interactive environment that supports the visual
      analysis of 3D patterns.

PMID- 22644870
TI  - Protein expression, aggregation, and triggered release from polymersomes as
      artificial cell-like structures.
AB  - Bringing droplets to life: A cytoskeletal protein (red dots, see scheme) is
      expressed in artificial cells composed of biocompatible polymersomes, which
      encapsulate expression machinery and amino acid building blocks. Release of the
      expressed proteins can be triggered by a negative osmotic shock.

PMID- 22644871
TI  - Mesenchymal stem cell-derived interleukin-6 and vascular endothelial growth
      factor promote breast cancer cell migration.
AB  - Several different cytokines and growth factors secreted by mesenchymal stem cells
      (MSCs) have been hypothesized to play a role in breast cancer progression. By
      using a small panel of breast cancer cell lines (MCF-7, T47D, and SK-Br-3 cells),
      we analyzed the role of interleukin-6 (IL-6) and vascular endothelial growth
      factor A (VEGF) in the cross-talk between MSCs and breast cancer cells. We
      performed migration assays in which breast cancer cells were allowed to migrate
      in response to conditioned medium from MSCs (MSCs-CM), in absence or in presence
      of the anti-VEGF antibody bevacizumab or an anti-IL-6 antibody, alone or in
      combination. We found that anti-VEGF and anti-IL-6 antibodies inhibited the
      migration of breast cancer cells and that the combination had an higher
      inhibitory effect. We next evaluated the effects of recombinant VEGF and IL-6
      proteins on breast cancer cell growth and migration. IL-6 and VEGF had not
      significant effects on the proliferation of breast carcinoma cells. In contrast,
      both VEGF and IL-6 significantly increased the ability to migrate of MCF-7, T47D
      and SK-Br-3 cells, with the combination showing a greater effect as compared with
      treatment with a single protein. The combination of VEGF and IL-6 produced in
      breast cancer cells a more significant and more persistent activation of MAPK,
      AKT, and p38MAPK intracellular signaling pathways. These results suggest that MSC
      secreted IL-6 and VEGF may act as paracrine factors to sustain breast cancer cell
      migration.

PMID- 22644872
TI  - Survey on recognition of post-mastectomy pain syndrome by breast specialist
      physician and present status of treatment in Japan.
AB  - BACKGROUND: Post-mastectomy pain syndrome (PMPS) is chronic pain after breast
      cancer surgery and is reported to influence quality of life (QOL). Although the
      results of a survey in Japan showed high incidence, at 21-65 %, many of the
      patients had never been treated for PMPS. One reason for this low treatment rate
      may be poor understanding of PMPS by medical personnel. In this study, we
      conducted the survey by using questionnaire to assess current treatment and the
      recognitions of the medical personnel. METHODS: We mailed a questionnaire to 647
      specialist members of the Breast Cancer Society. RESULTS: Of those, 34.7 %
      responsed. While PMPS was recognized by as much as 70.5 % of responding
      physicians, it was treated by as little as 47.7 % of the responders. In addition,
      while non-steroidal anti-inflammatory drugs (NSAIDs), which were ineffective in
      relieving PMPS, were used by 78.4 % of the responders, effective drugs were
      rarely used; therefore, treatment was considered ineffective by 69.5 %. This
      indicates that appropriate therapies are not widely used, and none of the current
      therapies are very effective. CONCLUSIONS: The results showed high recognition of
      PMPS pathology among physicians, but the treatment rate was as low as 47.7 %.
      NSAIDs were the main treatment, and the treatment effects were not satisfactory.
      It was revealed that currently appropriate treatment modalities have not been
      widely used. Education of physicians, distribution of treatment information and
      further studies are considered necessary for the spread of appropriate treatment
      modality.

PMID- 22644873
TI  - ACTH-secreting pheochromocytoma with false-negative ACTH immunohistochemistry.

PMID- 22644875
TI  - The risk of hematoma following extensive electromyography of the lumbar
      paraspinal muscles.
AB  - INTRODUCTION: The purpose of this study is to provide a controlled trial looking
      at the risk of paraspinal hematoma formation following extensive paraspinal
      muscle electromyography. METHODS: 54 subjects ages 55-80 underwent MRI of the
      lumbar spine before or shortly after electromyography using the paraspinal
      mapping technique. A neuroradiologist, blinded to the temporal relationship
      between the EMG and MRI, reviewed the MRIs to look for hematomas in or around the
      paraspinal muscles. RESULTS: Two MRIs demonstrated definite paraspinal hematomas,
      while 10 were found to have possible hematomas. All hematomas were < 15 mm, and
      none were close to any neural structures. There was no relationship between MRI
      evidence of hematoma and either the timing of the EMG or the use of aspirin or
      other nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Paraspinal
      electromyography can be considered safe in the general population and those
      taking nonsteroidal anti-inflammatory drugs.

PMID- 22644876
TI  - Palladium-catalyzed vicinal difunctionalization of internal alkenes:
      diastereoselective synthesis of diamines.
AB  - Internal affairs: the first general palladium-catalyzed intermolecular
      diamination of internal alkenes employs different nitrogen sources, which add to
      the alkene in a regio- and diastereoselective fashion. The resulting diamination
      products can be converted directly into a known ligand motif.

PMID- 22644874
TI  - Anti-fibrosis therapy and diabetic nephropathy.
AB  - Diabetes mellitus is rapidly becoming a global health issue that may overtake
      cancer during the next two decades as it covertly affects multiple organ systems
      that goes undiagnosed long after the onset. A number of complications are
      associated with poorly controlled hyperglycemia. Diabetic nephropathy is one of
      the most common complications of diabetes mellitus. Other than angiotensin
      converting enzyme (ACE) inhibitors and angiotensin receptor blocker (ARB) there
      is not much in the armamentarium with which to treat patients with overt diabetic
      nephropathy. Research points towards a multifactorial etiology and complex
      interplay of several pathogenic pathways that can contribute to the declining
      kidney function in diabetes. Patients with diabetic nephropathy (and with any
      chronic kidney disease) eventually develop kidney fibrosis. Despite the financial
      and labor investment spent on determining the basic mechanism of fibrosis, not
      much progress has been made in terms of therapeutic targets available to us
      today. This may be in part due to paucity in the experimental animal models
      available. However, there now seems to be a concerted effort from several
      pharmaceutical companies to develop a drug that would halt/delay the process of
      fibrosis, if not reverse it. This review discusses the current state of research
      in the field while staying within the context of diabetic nephropathy.

PMID- 22644877
TI  - Studies on gene polymorphisms in sports fancy fashion or important field of
      research?

PMID- 22644878
TI  - Hb(mass) for anti-doping purposes should be assessed in combination with
      hemoglobin and blood volume.

PMID- 22644879
TI  - Interaction of IFNlambdaR1 with TRAF6 regulates NF-kappaB activation and
      IFNlambdaR1 stability.
AB  - IFNlambdaR1 is a member of the class II cytokine receptor family, and it
      associates with IL-10R2 to form a functional receptor complex, IFNlambdaR. This
      receptor complex transduces signals from IFNlambdas (IFNlambda1, IFNlambda2, and
      IFNlambda3), promoting antiviral and antiproliferative activities similar to
      those of type I IFNs. In an effort to further understand signal transduction
      through IFNlambdaR1, we used bioinformatics analysis and identified a tumor
      necrosis factor receptor-associated factor 6 (TRAF6)-binding motif in the
      intracellular domain of IFNlambdaR1. In subsequent immunoprecipitation and GST
      pull-down assays, IFNlambdaR1 was shown to immunoprecipitate with TRAF6 and was
      pulled down by GST-TRAF6. Endogenous IFNlambdaR1 and TRAF-6 interaction implies
      that these proteins really interact in the cells. This interaction was abrogated
      upon mutation of the TRAF6-binding motif in IFNlambdaR1. Furthermore, the
      interaction between IFNlambdaR1 and TRAF6 inhibited TRAF6-induced NF-kappaB
      activation, likely due to a reduction in TRAF6 autoubiquitination. Moreover, co
      expression of IFNlambdaR1 with TRAF6 significantly increased the stability of
      IFNlambdaR1, thereby prolonging its half-life and enhancing its steady-state
      level in cultured cells.

PMID- 22644880
TI  - When is irritable bowel syndrome not irritable bowel syndrome? Diagnosis and
      treatment of chronic functional abdominal pain.
AB  - Functional abdominal pain syndrome (FAPS) is a distinct chronic gastrointestinal
      (GI) pain disorder characterized by the presence of constant or frequently
      recurring abdominal pain that is not associated with eating, change in bowel
      habits, or menstrual periods. The pain experience in FAPS is predominantly
      centrally driven as compared to other chronic painful GI conditions such as
      inflammatory bowel disease and chronic pancreatitis where peripherally acting
      factors play a major role in driving the pain. Psychosocial factors are often
      integrally associated with the disorder and can pose significant challenges to
      evaluation and treatment. Patients suffer from considerable loss of function,
      which can drive health care utilization. Treatment options are limited at best
      with most therapeutic regimens extrapolated from pain management of other
      functional GI disorders and chronic pain conditions. A comprehensive approach to
      management using a biopsychosocial construct and collaboration with pain
      specialists and psychiatry is most beneficial to the management of this disorder.

PMID- 22644881
TI  - Posterior spinal fusion in adolescent idiopathic scoliosis with or without
      intraoperative cell salvage system: a retrospective comparison.
AB  - This study investigates efficacy and safety of routine cell salvage system use in
      adolescent idiopathic scoliosis patients undergoing primary posterior spinal
      fusion surgery with segmental spinal instrumentation. Forty-five consecutive
      adolescent idiopathic scoliosis patients undergoing posterior spinal fusion by
      two surgeons at a single hospital were studied. Intraoperative cell salvage
      system was used in 23 patients, and the control group was 22 patients who
      underwent surgery without cell salvage system. The cell salvage system was the
      Haemonetics Cell Saver 5. The primary outcome measures were intraoperative and
      perioperative allogeneic transfusion rate, difference between preoperative and
      discharge Hg and Hct levels. Average patient age was 14.65 +/- 1.49 in cell saver
      group and 13.86 +/- 2.0 in control group. In cell saver group, average
      intraoperative autotransfusion was 382.1 +/- 175 ml. Average perioperative
      allogeneic blood transfusion need was 1.04 +/- 0.7 unit in cell saver group and
      2.5 +/- 1.14 unit in control group. No transfusion reactions occurred in either
      group. Average hemoglobin level in cell saver group was 10.7 +/- 0.86 and average
      hemoglobin level in control group was 10.7 +/- 0.82 on discharge. Cell saver
      reduces perioperative transfusion rate in patients undergoing posterior spinal
      fusion for adolescent idiopathic scoliosis.

PMID- 22644882
TI  - Suspected paradoxical undressing in a homicide case.
AB  - Paradoxical undressing is a phenomenon associated with fatalities due to severe
      hypothermia, which is characterized by the act of active undressing, despite low
      ambient temperatures, as a consequence of peripheral vasodilation. A 51-year-old
      man was found lying naked and inanimate on a road. Articles of his clothing were
      scattered in surrounding bushes. A nearby handrail showed a partially washed away
      bloodstain pattern. A forensic autopsy was used to distinguish whether death was
      due to a hypothermic fatality or whether the deceased was a victim of an accident
      or homicide. Medicolegal autopsy revealed craniofacial dissociation with injuries
      to the thorax and extremities and established choking/asphyxia due to deep
      aspiration of blood in combination with external blood loss as the cause of
      death. In the absence of hypothermia-related signs and toxicological findings the
      case was considered to be a homicide. Police investigation led to the conviction
      of a man who confessed to having kicked and hit the victim and forced him to take
      off his clothes in a humiliation-related scenario.

PMID- 22644883
TI  - Management of medicolegal natural deaths from hemopericardium or hemothorax using
      postmortem CT scanning.
AB  - At the Victorian Institute of Forensic Medicine the forensic pathologist provides
      expert medical advice to the Coroner. Cases of natural death from hemopericardium
      and hemothorax are reasonably common in the forensic setting and are readily
      identifiable on postmortem CT (PMCT) scanning. The management of these cases
      raises interesting and challenging issues for the forensic pathologist. We
      present three cases in which PMCT angiography was useful in the management of
      each individual case and illustrate the potential of the technique in medico
      legal death investigation.

PMID- 22644884
TI  - Chemoselective ligation of sulfinic acids with aryl-nitroso compounds.
AB  - Making a comeback: The inefficient condensation of sulfinic acid and aryl nitroso
      compounds has been transformed into a chemoselective process that converts
      sulfinic acid into stable cyclic sulfonamide analogues (see scheme). This
      ligation proceeds rapidly under aqueous conditions in high yield, and lays the
      groundwork for the development of sulfinic acid detection methods in biological
      systems.

PMID- 22644885
TI  - Genotoxic effects of glyphosate or paraquat on earthworm coelomocytes.
AB  - The potential genotoxicity (nuclear anomalies, damage to single-strand DNA) and
      pinocytic adherence activity of two (glyphosate-based and paraquat-based)
      commercial herbicides to earthworm coelomocytes (immune cells in the coelomic
      cavity) were assessed. Coelomocytes were extracted from earthworms (Pheretima
      peguana) exposed to concentrations <LC50 of glyphosate-based or paraquat-based
      herbicides on filter paper for 48 h. Three assays were performed: Micronucleus
      (light microscopy count of micronuclei, binuclei, and trinuclei), Comet
      (epifluorescent microscope and LUCIA image analyzer measure of tail DNA %, tail
      length, and tail moment), and Neutral Red (to detect phagocytic or pinocytic
      activity). The LC50 value for paraquat was 65-fold lower than for glyphosate
      indicating that paraquat was far more acutely toxic to P. peguana. There were
      significant (P < 0.05) differences from the control group in total coelomocyte
      micronuclei, binuclei, and trinuclei frequencies of earthworms exposed to
      glyphosate at 25 * 10(-1) (10(-3) LC50) and paraquat at 39 * 10(-5) (10(-4) LC50)
      MUg cm(-2) filter paper. In earthworms exposed to glyphosate, no differences in
      tail DNA%, tail length, and tail moment of coelomocytes were detected. In
      contrast, for paraquat at 10(-1) LC50 concentration, there were significant (P <
      0.05) differences between tail DNA % and tail length, and at LC50 concentration,
      tail moment was also significantly different when compared with controls. A
      decline in pinocytic adherence activity in coelomocytes occurred on exposure to
      glyphosate or paraquat at 10(-3) LC50 concentration. This study showed that, at
      concentrations well below field application rates, paraquat induces both
      clastogenic and aneugenic effects on earthworm coelomocytes whereas glyphosate
      causes only aneugenic effects and therefore does not pose a risk of gene mutation
      in this earthworm.

PMID- 22644886
TI  - Assessing the clinical needs for point of care technologies in neurologic
      emergencies.
AB  - BACKGROUND: Neurologic emergencies are common, frequently devastating, and
      benefit from timely diagnosis and treatment.  Point of care (POC) technologies
      have the potential to assist clinicians caring for these patients.  In order to
      prioritize development of new POC testing, a thorough assessment of clinical
      needs is required.  We describe the methods of the clinical needs assessment
      (CNA) process and provide the initial findings of a CNA for POC technologies in
      neurologic emergencies performed to support a National Institute of Biomedical
      Imaging and Bioengineering (NIBIB) initiative. METHODS: CNA is an iterative
      process.  An initial survey instrument was developed through consensus by a multi
      disciplinary panel and underwent internal validation through beta-testing and
      face-validity assessment.  This survey was distributed at the national meetings
      of several academic medical societies and results were used to redesign of the
      survey tool for broader distribution.  Analysis of responses from the revised
      survey supported the release of a request for proposals (RFP) in 2010.  Survey
      revision continues, and expanded CNA efforts with focus groups are being designed
      in anticipation of another RFP in 2012. RESULTS: The initial survey identified
      six areas of clinical need and two domains of interest.  The revised version
      gathered additional responses but no new domains or areas of clinical need were
      identified. The resultant RFP generated 23 letters of intent from industry and
      academic institutions, of which three were chosen for funding. CONCLUSIONS:
      Assessing clinical needs is a necessary first step in developing new
      technologies.  A multi-faceted approach assures that the views of interested
      stakeholders are represented and can influence success.

PMID- 22644887
TI  - Continuous cerebral blood flow autoregulation monitoring in patients undergoing
      liver transplantation.
AB  - BACKGROUND: Clinical monitoring of cerebral blood flow (CBF) autoregulation in
      patients undergoing liver transplantation may provide a means for optimizing
      blood pressure to reduce the risk of brain injury. The purpose of this pilot
      project is to test the feasibility of autoregulation monitoring with transcranial
      Doppler (TCD) and near-infrared spectroscopy (NIRS) in patients undergoing liver
      transplantation and to assess changes that may occur perioperatively. METHODS: We
      performed a prospective observational study in 9 consecutive patients undergoing
      orthotopic liver transplantation. Patients were monitored with TCD and NIRS. A
      continuous Pearson's correlation coefficient was calculated between mean arterial
      pressure (MAP) and CBF velocity and between MAP and NIRS data, rendering the
      variables mean velocity index (Mx) and cerebral oximetry index (COx),
      respectively. Both Mx and COx were averaged and compared during the dissection
      phase, anhepatic phase, first 30 min of reperfusion, and remaining reperfusion
      phase. Impaired autoregulation was defined as Mx >= 0.4. RESULTS: Autoregulation
      was impaired in one patient during all phases of surgery, in two patients during
      the anhepatic phase, and in one patient during reperfusion. Impaired
      autoregulation was associated with a MELD score >15 (p = 0.015) and postoperative
      seizures or stroke (p < 0.0001). Analysis of Mx categorized in 5 mmHg bins
      revealed that MAP at the lower limit of autoregulation (MAP when Mx increased to
      >= 0.4) ranged between 40 and 85 mmHg. Average Mx and average COx were
      significantly correlated (p = 0.0029). The relationship between COx and Mx
      remained when only patients with bilirubin >1.2 mg/dL were evaluated (p =
      0.0419). There was no correlation between COx and baseline bilirubin (p = 0.2562)
      but MELD score and COx were correlated (p = 0.0458). Average COx was higher for
      patients with a MELD score >15 (p = 0.073) and for patients with a neurologic
      complication than for patients without neurologic complications (p = 0.0245).
      CONCLUSIONS: These results suggest that autoregulation is impaired in patients
      undergoing liver transplantation, even in the absence of acute, fulminant liver
      failure. Identification of patients at risk for neurologic complications after
      surgery may allow for prompt neuroprotective interventions, including directed
      pressure management.

PMID- 22644888
TI  - Aggressive CSF diversion reverses delayed cerebral ischemia in aneurysmal
      subarachnoid hemorrhage: a case report.
AB  - BACKGROUND: External ventricular drain (EVD) placement temporarily provides
      cerebrospinal fluid (CSF) diversion and is indicated in patients with aneurysmal
      subarachnoid hemorrhage (aSAH) to relieve hydrocephalus. METHODS: Case report.
      RESULTS: A 56-year-old woman was admitted to our hospital with aSAH complicated
      by acute hydrocephalus. An EVD was placed and set to 15 mmHg. After nearly 72 h,
      she clinically deteriorated. A computed tomography (CT) perfusion scan showed
      hypoperfusion in the watershed regions in both hemispheres and CT angiogram
      showed mild segmental arterial narrowings. After the EVD was lowered to 5 mmHg,
      the radiologic perfusion abnormalities and clinical symptoms resolved.
      CONCLUSIONS: We postulate a mechanism by which CSF diversion could decrease the
      risk of delayed cerebral ischemia after aSAH: CSF drainage at low levels of
      intracranial pressure (e.g., 5 mmHg) could improve blood flow in the
      microcirculation, and thus improve tissue perfusion.

PMID- 22644890
TI  - Feasibility and benefits of a school-based academic and counseling program for
      older school-age students with asthma.
AB  - An asthma education program for older school-age students with asthma was
      developed in collaboration with school personnel, healthcare professionals, and
      community partners. Feasibility and benefits were evaluated using a single-group,
      prospective, quasi-experimental design. The convenience sample, consisting of 28
      grade 6 and 7 students with asthma, had 50% males, a diverse racial background,
      and a wide range of incomes. Feasibility and benefits were demonstrated by
      comparing pre-intervention to 1- and 12-month post-intervention evaluation of
      students who completed more than 70% of the 10 sessions. Statistically
      significant improvements in cognitive, behavioral, psychosocial, and quality of
      life outcomes were seen from pre-intervention to 1-month post-intervention (all p
      < .03). Severity of asthma significantly improved from 1- to 12-month post
      intervention (p= .04).

PMID- 22644891
TI  - Stereoselective total syntheses of herbicidin C and aureonuclemycin through late
      stage glycosylation.
AB  - Better late than never! Two herbicidins, members of an important family of
      nucleoside antibiotics, have been synthesized for the first time. The route
      integrates a stereoselective C-glycosylation with several reagent-controlled
      stereoselective transformations and a surprisingly facile and highly
      diastereoselective late-stage N-glycosylation.

PMID- 22644889
TI  - Body composition and skeletal health: too heavy? Too thin?
AB  - The relationship between body composition and skeletal metabolism has received
      growing recognition. Low body weight is an established risk factor for fracture.
      The effect of obesity on skeletal health is less well defined. Extensive studies
      in patients with anorexia nervosa and obesity have illuminated many of the
      underlying biologic mechanisms by which body composition modulates bone mass.
      This review examines the relationship between body composition and bone mass
      through data from recent research studies throughout the weight spectrum ranging
      from anorexia nervosa to obesity.

PMID- 22644892
TI  - Thrombotic thrombocytopenic purpura precipitated by thyrotoxicosis.
AB  - Thrombotic thrombocytopenic purpura (TTP) may be seen in association with
      autoimmune disorders such as immune hemolytic anemia and systemic lupus
      erythematosus, but rarely has it been associated with Graves' disease. We report
      one such case of a woman with new-onset thyrotoxicosis caused by Graves' disease,
      who abruptly developed TTP, confirmed by low serum ADAMTS-13 value. She had a
      dramatic response to plasma exchange, with remission of TTP. Definitive treatment
      with radioactive iodine resulted in euthyroidism and has prevented recurrence of
      TTP.

PMID- 22644900
TI  - Effects of PACAP on intracellular signaling pathways in human retinal pigment
      epithelial cells exposed to oxidative stress.
AB  - The integrity of retinal pigment epithelial cells is critical for photoreceptor
      survival and vision. Pituitary adenylate cyclase activating polypeptide (PACAP)
      exerts retinoprotective effects against several types of injuries in vivo,
      including optic nerve transection, retinal ischemia, excitotoxic injuries, UVA
      induced lesion, and diabetic retinopathy. In a recent study, we have proven that
      PACAP is also protective in oxidative stress-induced injury in human pigment
      epithelial cells (ARPE-19 cells). The aim of the present study was to investigate
      the possible mechanisms of this protection. ARPE cells were exposed to a 24-h
      hydrogen peroxide treatment. Expressions of kinases and apoptotic markers were
      studied by complex array kits and Western blot. Oxidative stress induced the
      activation of several apoptotic markers, including Bad, Bax, HIF-1alpha, several
      heat shock proteins, TNF-related apoptosis-inducing ligand, and Fas-associated
      protein with death domain, while PACAP treatment decreased them. The changes in
      the expression of MAP kinases showed that PACAP activated the protective ERK1/2
      and downstream CREB, and decreased the activation of the pro-apoptotic p38MAPK
      and c-Jun N-terminal kinase, an effect opposite to that observed with only
      oxidative stress. Furthermore, PACAP increased the activation of the protective
      Akt pathway. In addition, the effects of oxidative stress on several other
      signaling molecules were counteracted by PACAP treatment (Chk2, Yes, Lyn,
      paxillin, p53, PLC, STAT4, RSK). These play a role in cell death, cell cycle,
      inflammation, adhesion, differentiation and proliferation. In summary, PACAP,
      acting at several levels, influences the balance between pro- and anti-apoptotic
      factors in favor of anti-apoptosis, thereby providing protection in oxidative
      stress-induced injury of human retinal pigment epithelial cells.

PMID- 22644901
TI  - Developing effective cancer pain education programs.
AB  - Pain is prevalent, burdensome, and undertreated in individuals with cancer across
      the disease trajectory. Providing patients and family caregivers with
      psychosocial support and education to manage cancer pain is a core component of
      quality care that can result in significant clinical benefit. In this review, we:
      (1) outline an approach for developing and assessing the effectiveness of
      education programs for adults with cancer pain; (2) discuss considerations for
      tailoring programs to the needs of diverse populations and those with limited
      health literacy skills; (3) describe the resource needs and costs of developing a
      program; (4) highlight innovative approaches to cancer pain education. We
      conclude with recommendations for future research and the next generation of
      educational interventions.

PMID- 22644902
TI  - The role of corticosteroids in the treatment of pain in cancer patients.
AB  - Pain is one of the most frequent and most distressing symptoms in the course of
      cancer. The management of pain in cancer patients is based on the concept of the
      World Health Organization (WHO) analgesic ladder and was recently updated with
      the EAPC (European Association for Palliative Care) recommendations. Cancer pain
      may be relieved effectively with opioids administered alone or in combination
      with adjuvant analgesics. Corticosteroids are commonly used adjuvant analgesics
      and play an important role in neuropathic and bone pain treatment. However, in
      spite of the common use of corticosteroids, there is limited scientific evidence
      demonstrating their efficacy in cancer patients with pain. The use of
      corticosteroids in spinal cord compression, superior vena cava obstruction,
      raised intracranial pressure, and bowel obstruction is better established than in
      other nonspecific indications. This review aims to present the role of steroids
      in pain and management of other symptoms in cancer patients according to the
      available data, and discusses practical aspects of steroid use.

PMID- 22644903
TI  - Treatment of perimenstrual migraine with triptans: an update.
AB  - Pure menstrual migraine (PMM) and menstrually related migraine (MRM) are
      difficult challenges in migraine management. Triptans are a class of highly
      selective serotonin receptor agonists, which interfere with the pathogenesis of
      migraine and are effective in relieving the associated neurovegetative symptoms.
      In recent years triptans have been extensively proposed for the treatment of
      severe, disabling, and recurrent perimenstrual migraine attacks. This review
      summarizes the different levels of recommendations for the use of triptans in the
      treatment of perimenstrual migraine. This review is also intended to offer an
      updated reasonable guide to physicians treating perimenstrual migraine in daily
      practice.

PMID- 22644905
TI  - Biosupramolecular nanowires from chlorophyll dyes with exceptional charge
      transport properties.
AB  - Conductive tubes: Self-assembled nanotubes of a bacteriochlorophyll derivative
      are reminiscent of natural chlorosomal light-harvesting assemblies. After
      deposition on a substrate that consists of a non-conductive silicon oxide surface
      (see picture, brown) and contacting the chlorin nanowires to a conductive polymer
      (yellow), they show exceptional charge-transport properties.

PMID- 22644906
TI  - Prospective, multicenter European study of the GORE flow reversal system for
      providing neuroprotection during carotid artery stenting.
AB  - BACKGROUND: Embolic protection devices (EPDs) are used to provide protection
      against brain embolization during carotid artery stenting (CAS) to treat carotid
      artery stenosis, but the optimal type of EPD has not been determined. Distally
      positioned filters are commonly used but do not provide protection during
      crossing of the lesion. This prospective, multicenter study investigated a
      proximally placed device (GORE Flow Reversal System) that reverses blood flow in
      the internal carotid artery during CAS, thereby directing emboli away from the
      brain. METHODS: Outcomes in 122 patients (28% symptomatic), who underwent CAS
      using the flow reversal system were assessed (intention-to-treat analysis). The
      primary endpoint was a major adverse event (MAE; defined as death or stroke)
      within 30 days of CAS. The secondary endpoint was a myocardial infarction (MI) or
      nonstroke-related neurologic event within 30 days. RESULTS: The flow reversal
      system could not be used in one patient because of severe vessel tortuosity and
      in two patients (1.6%) because of intolerance. The 30-day MAE rate and the
      secondary endpoint rate were each 1.6%. No patient in the series died or had an
      MI within 30 days. No patient who was symptomatic before CAS had an MAE. One
      symptomatic and one asymptomatic patient had a transient ischemic attack.
      CONCLUSIONS: Use of the GORE Flow Reversal System during CAS had a high rate of
      technical success and low 30-day rates of adverse neurologic and cardiac events.

PMID- 22644907
TI  - P2X7 receptor activation leads to increased cell death in a radiosensitive human
      glioma cell line.
AB  - Gliomas are the most lethal tumors of central nervous system. ATP is an important
      signaling molecule in CNS and it is a selective P2X7 purinergic receptor ligand
      at high concentrations. Herein, we investigated whether the activation of P2X7R
      might be implicated in death of a radiosensitive human glioma lineage. The
      effects of P2X7R agonists (ATP and BzATP) and irradiation (2 Gy) on glioma cells
      were analyzed by MTT assay and annexin-V/PI determination, whereas mRNA and
      protein P2X7R expression was assessed by qRT-PCR and flow cytometry,
      respectively. P2X7R pore formation was functionality examined by analyzing
      ethidium bromide uptake. The human glioma cells U-138 MG and U-251 MG were
      resistant to death when treated with either ATP (5 mM) or BzATP (100 MUM), but
      the radiosensitive M059J glioma cells displayed a significant decrease of cell
      viability (32.4 +/- 4.1 % and 25.6 +/- 3.3 %, respectively). The M059J lineage
      expresses significantly higher mRNA P2X7R levels when compared to the U-138 MG
      and U-251 cell lines (0.40 +/- 0.00; 0.28 +/- 0.01, and 0.31 +/- 0.01,
      respectively), and irradiation upregulated P2X7R expression (0.55 +/- 0.08) in
      this lineage. Noteworthy, P2X7R protein doubled after irradiation on M059J
      lineage, and increased in 50 % and 42.6 % when comparing M059J-irradiated to
      irradiated U-138 MG and U-251 MG cells, respectively. Ethidium bromide uptake was
      significantly increased in 104 % and 77.8 % when comparing M059J to U-138 MG and
      U-251MG, respectively. Finally, the selective P2X7R antagonist A740003
      significantly decreased the cell death caused by irradiation. We provide novel
      evidence indicating that M059J human glioma cell line is ATP-P2X7R sensitive,
      pointing out the relevance of the purinergic P2X7R on glioma radiosensitivity.

PMID- 22644917
TI  - Growth arrest-specific homeobox is associated with poor survival in patients with
      hepatocellular carcinoma.
AB  - Growth arrest-specific homeobox (GAX) codes for a transcription factor and plays
      a crucial role in many human cancers. Previous tumor studies have shown GAX may
      act as a suppressor of growth, invasion, and metastasis. However, little is known
      as to its role in hepatocellular carcinoma (HCC). Our aim was to investigate the
      expression of GAX in HCC and to make correlations with clinicopathologic
      features. Twenty-five pairs of HCC and adjacent non-tumor tissues, and six normal
      liver tissues were collected for GAX detection by Western blotting and real-time
      PCR analysis. Immunohistochemistry was used to determine the expression of GAX in
      HCC and adjacent non-tumor tissues from 96 patients. Reduced expression of GAX
      was significantly associated with Edmondson stage, vascular invasion, and capsule
      invasion. Moreover, Kaplan-Meier curves showed that lower GAX expression was
      associated with shorter overall survival and disease-free survival in HCC
      patient. In conclusion, our study demonstrates for the first time that
      downregulated expression of GAX is an independent prognostic factor and is
      correlated with poor survival in HCC patients.

PMID- 22644919
TI  - Sex differences in the functional and structural neuroanatomy of dental phobia.
AB  - Although dental phobia is a common mental disorder, which afflicts both men and
      women, little is known about sex differences at the neural level. Patients
      suffering from dental phobia (20 men, 25 women) and healthy controls (18 men, 23
      women) participated in a functional magnetic resonance imaging (fMRI) experiment.
      They were shown pictures depicting dental treatment, generally fear-eliciting,
      disgust-eliciting and neutral contents. After the fMRI experiment, the
      participants rated the affective value of the pictures. Additionally, grey matter
      volume (GMV) was compared between patients and controls, as well as between the
      sexes. Male and female patients responded differently to the phobogenic pictures.
      Women showed greater activation of the caudate nucleus, whereas men exhibited
      enhanced dorsolateral prefrontal cortex (DLPFC) involvement. Their DLPFC
      activation was negatively correlated with experienced arousal. Dentophobic
      females were characterized by a greater caudate volume relative to phobic males.
      The GMV of this structure was positively correlated with experienced arousal
      during exposure and symptom severity, only in female patients. This study
      provides first evidence of sex-specific brain activation and structure in
      patients suffering from dental phobia. The neural pattern during symptom
      provocation as well as the brain structural specificity might mirror different
      attention and self-control strategies of both sexes. The consideration of such
      differences could contribute to greater effectiveness in treating dental phobia.

PMID- 22644920
TI  - Apoptosis contributes to placode morphogenesis in the posterior placodal area of
      mice.
AB  - In the embryonic head of vertebrates, neurogenic and non-neurogenic ectodermal
      placodes arise from the panplacodal primordium. Whether and how growth processes
      of the ectodermal layer, changes in the transcriptional precursor cell profile,
      or positional changes among precursor cells contribute to interplacodal boundary
      formation is subject to intense investigation. We demonstrate that large scale
      apoptosis in the multiplacodal posterior placodal area (PPA) of C57BL/6 mice
      assists in the segregation of otic and epibranchial placodes. Complex patterns of
      interplacodal apoptosis precede and parallel the structural individualization of
      high-grade thickened placodes, with the fundamental separation between otic and
      epibranchial precursor cells being seemingly prevalent. Interplacodal apoptosis
      between the emerging epibranchial placodes, which express Neurogenin2 prior to
      their complete structural individualization, comes out most strongly between the
      epibranchial placodes 1 and 2. Apoptosis then moves from interplacodal to
      intraplacodal positions in dorsal and, with a delay, ventral parts of the
      epibranchial placodes. Intraplacodal apoptosis appears to exert corrective
      actions among premigratory neuroblasts, and helps to eliminate the epibranchial
      placodes. The present findings confirm and extend earlier observations in Tupaia
      belangeri (Washausen et al. in Dev Biol 278:86-102, 2005), regarded as an
      intermediate between primates and other eutherian orders. Having now available
      maps of apoptosis in the PPA of embryonic mice, further investigations into the
      functions of inter- and intraplacodal apoptosis can be carried out in an
      experimentally and genetically more accessible mammalian model organism.

PMID- 22644918
TI  - Tumor microRNA-335 expression is associated with poor prognosis in human glioma.
AB  - MicroRNA-335 (miR-335), as a transcript of genomic region chromosome 7q32.2, acts
      as a tumor suppressor or tumor promoter in various human malignancies.
      Especially, it has been reportedly shown to be an oncogene in human glioma cell
      line in vitro, but its expression in human glioma tissues is not yet determined.
      The aim of this study was to investigate the clinical significance of miR-335
      expression in glioma. MiR-335 expression in human gliomas and nonneoplastic brain
      tissues was measured by real-time quantitative RT-PCR assay. The association of
      miR-335 expression with clinicopathological factors and prognosis of glioma
      patients was statistically analyzed. The expression level of miR-335 in glioma
      tissues was significantly higher than that in corresponding nonneoplastic brain
      tissues (P < 0.001). In addition, high miR-335 expression was significantly
      associated with a higher WHO grade (P = 0.001). Survival analysis demonstrated
      that patients with high miR-335 expression tumors had significantly shorter
      survival times than those with low miR-335 expression tumors (P = 0.01) and that
      miR-335 was an independent prognostic factor (P = 0.02). Especially, subgroup
      analyses according to tumor histologic grade revealed that the mean survival time
      of patients with high grade (III-IV) was significantly worse for high miR-335
      expression group than for low miR-335 expression group (P = 0.002), but no
      significant difference was found for patients with WHO grade I-II (P = 0.16).
      These results indicated that miR-335 expression was increased in human gliomas
      and was associated with advanced tumor progression. Furthermore, miR-335
      expression was demonstrated for the first time to be an independent marker for
      predicting the clinical outcome of patients with gliomas.

PMID- 22644921
TI  - Erroneous computer electrocardiogram interpretation of atrial fibrillation and
      its clinical consequences.
AB  - BACKGROUND: The aim of this study was to determine the frequency and nature of
      errors made by computer electrocardiogram (ECG) analysis of atrial fibrillation
      (AF), and the clinical consequences. HYPOTHESIS: Computer software for
      interpreting ECGs has advanced. METHODS: A total of 10279 ECGs were collected,
      automatically interpreted by the built-in ECG software, and then reread by 2
      cardiologists. AF-related ECGs were classified into 3 groups: overinterpreted AF
      (rhythms other than AF interpreted as AF), misinterpreted AF (AF interpreted as
      rhythms other than AF), and true AF (AF interpreted as AF by both computer ECG
      interpretation and cardiologists). RESULTS: There were 1057 AF-related ECGs from
      409 patients. Among these, 840 ECGs (79.5%) were true AF. Overinterpretation
      occurred in 98 (9.3%) cases. Sinus rhythm and sinus tachycardia with premature
      atrial contraction and/or baseline artifact and sinus arrhythmia were commonly
      overinterpreted as AF. Heart rate <=60 bpm and baseline artifact significantly
      increased the likelihood of overinterpreted AF. Misdiagnosis occurred in 119
      (11.3%) cases, in which AF was usually misdiagnosed as sinus or supraventricular
      tachycardia. The presence of tachycardia and low-amplitude atrial activity
      significantly increased the likelihood of misdiagnosis of AF. Among the erroneous
      computer ECG interpretations, 17 cases (7.8%) were not corrected by the ordering
      physicians and/or repeat computer-ECG interpretation; inappropriate follow-up
      studies or treatments of the patients were undertaken with no serious sequelae.
      CONCLUSIONS: Erroneous computer ECG interpretation of AF was not rare. Attention
      should be concentrated on educating physicians about ECG appearance and
      confounding factors of AF, along with ongoing quality control of built-in
      software for automatic ECG interpretation.

PMID- 22644922
TI  - Crystal-plane-dependent photoluminescence of pentacene 1D wire and 2D disk
      crystals.
AB  - Down to the wire: Pentacene exhibits crystal-plane-dependent photoluminescence
      (PL) activity, as demonstrated in highly crystalline 1D wires and 2D disks, which
      were selectively synthesized using the vaporization-condensation
      recrystallization (VCR) process. Although pentacene 1D wires and 2D disks have
      identical triclinic crystal structures, PL activity is observed only from
      pentacene 1D wires owing to the presence of "PL-active" (010) planes.

PMID- 22644923
TI  - Metabolomics has great potential for clinical and nutritional care and research
      with exotic animals.
AB  - This essay explores the potential of metabolomics for exotic animal research in a
      zoological setting. Metabolomics is a suite of analytical tools aimed at gaining
      a holistic understanding of animal metabolism without prior knowledge of the
      compounds to be measured. These metabolic fingerprints can be used to define
      normal metabolism for an unstudied species, to characterize the metabolic
      deviation of diseased animals from the normal state over time, to identify
      biomarker compounds that best capture such deviations, and to measure the
      metabolic impact of clinical and nutritional interventions. Two approaches,
      nuclear magnetic resonance (NMR) and mass spectrometry (MS) provide large amounts
      of complimentary pure and applied biological data. Metabolomic methods hold great
      potential for researchers, clinicians, and nutritionists studying exotic and
      aquatic animals because they can produce a huge data return on research effort,
      and because they do not require much a priori knowledge of the animals'
      metabolism, which is so often then case in zoological settings.

PMID- 22644933
TI  - Amplification of GC-rich DNA for high-throughput family-based genetic studies.
AB  - Researchers face a significant problem in PCR amplification of DNA fragments with
      high GC contents. Analysis of these regions is of importance since many
      regulatory regions of different genes and their first exons are GC-rich. There
      are a large number of protocols for amplification of GC-rich DNA, some of which
      perform well but are costly. Most of the economical protocols fail to perform
      consistently, especially on products with >80 % GC contents and a size of >300
      bp. One of these protocols requires multiple additions of DNA polymerase during
      thermal cycling which therefore rules out its utility if a large number of
      samples have to be amplified. We have established a method for simultaneous
      amplification of specific PCR products from a large number of human DNA samples
      using general laboratory reagents. These amplicons have GC contents ranging from
      65-85 % and sizes up to 870 bp. The protocol uses a PCR buffer containing co
      solvents including 2-mercaptoethanol and bovine serum albumin for amplification
      of DNA. A specific thermal cycling profile is also used which incorporates a high
      annealing temperature in the first 7 cycles of the reactions. The PCR products
      are suitable for different molecular biology applications including sequencing.

PMID- 22644934
TI  - Angiotensin-(1-7) reduces proliferation and angiogenesis of human prostate cancer
      xenografts with a decrease in angiogenic factors and an increase in sFlt-1.
AB  - BACKGROUND: Prostate cancer is the most frequently diagnosed malignancy and the
      second-leading cause of cancer death in men. The purpose of this study was to
      determine the anti-proliferative and anti-angiogenic efficacy of angiotensin-(1
      7) [Ang-(1-7)], an endogenous peptide hormone, in human prostate cancer
      xenografts. METHODS: Human LNCaP prostate cancer cells were injected into the
      flank of athymic mice and tumors were treated with Ang-(1-7) for 54 days. Tumor
      growth and angiogenesis were determined by immunohistochemistry and western blot
      hybridization. RESULTS: Ang-(1-7) markedly reduced the volume and wet weight of
      LNCaP xenograft tumors. Histological analysis of tumor sections from saline
      treated mice showed increased Ki67 immunoreactivity and enhanced phosphorylation
      of the MAP kinases ERK1/2 compared to tumors from Ang-(1-7)-treated mice,
      suggesting that the heptapeptide reduces cell proliferation. Intratumoral vessel
      density was decreased in Ang-(1-7)-treated mice with an associated reduction in
      vascular endothelial growth factor (VEGF) and placental growth factor (PlGF),
      suggesting that the heptapeptide attenuates vascularization by reducing
      angiogenic factors. Ang-(1-7) administration markedly increased the soluble
      fraction of VEGF receptor 1 (sFlt-1), with a concomitant reduction in VEGF
      receptors 1 and 2. sFlt-1 serves as a decoy receptor that traps VEGF and PlGF,
      making the ligands unavailable to membrane-bound VEGF receptors and preventing
      activation of pro-angiogenic signaling. CONCLUSIONS: The decrease in PlGF and
      VEGF coupled with the increase in sFlt-1 suggests that Ang-(1-7) may serve as a
      novel anti-angiogenic therapy for prostate cancer. Further, the pleiotropic
      mechanisms of action by Ang-(1-7) may limit angiogenic resistance that occurs
      with VEGF inhibitors or receptor blockers.

PMID- 22644939
TI  - Toward the establishment of standardized in vitro tests for lipid-based
      formulations, part 1: method parameterization and comparison of in vitro
      digestion profiles across a range of representative formulations.
AB  - The Lipid Formulation Classification System Consortium is an industry-academia
      collaboration, established to develop standardized in vitro methods for the
      assessment of lipid-based formulations (LBFs). In this first publication,
      baseline conditions for the conduct of digestion tests are suggested and a series
      of eight model LBFs are described to probe test performance across different
      formulation types. Digestion experiments were performed in vitro using a pH-stat
      apparatus and danazol employed as a model poorly water-soluble drug. LBF
      digestion (rate and extent) and drug solubilization patterns on digestion were
      examined. To evaluate cross-site reproducibility, experiments were conducted at
      two sites and highly consistent results were obtained. In a further refinement,
      bench-top centrifugation was explored as a higher throughput approach to
      separation of the products of digestion (and compared with ultracentrifugation),
      and conditions under which this method was acceptable were defined. Drug
      solubilization was highly dependent on LBF composition, but poorly correlated
      with simple performance indicators such as dispersion efficiency, confirming the
      utility of the digestion model as a means of formulation differentiation.

PMID- 22644940
TI  - Poly(2,5-dimercapto-1,3,4-thiadiazole) as a cathode for rechargeable lithium
      batteries with dramatically improved performance.
AB  - Organosulfur compounds with multiple thiol groups are promising for high
      gravimetric energy density electrochemical energy storage. We have synthesized a
      poly(2,5-dimercapto-1,3,4-thiadiazole) (PDMcT)/poly(3,4-ethylenedioxythiophene)
      (PEDOT) composite cathode for lithium-ion batteries with a new method and
      investigated its electrochemical behavior by charge/discharge cycles and cyclic
      voltammetry (CV) in an ether-based electrolyte. Based on a comparison of the
      electrochemical performance with a carbonate-based electrolyte, we found a much
      higher discharge capacity, but also a very attractive cycling performance of
      PDMcT by using a tetra(ethylene glycol) dimethyl ether (TEGDME)-based
      electrolyte. The first discharge capacity of the as-synthesized PDMcT/PEDOT
      composite approached 210 mAh g(-1) in the TEGDME-based electrolyte. CV results
      clearly show that the redox reactions of PDMcT are highly reversible in this
      TEGDME-based electrolyte. The reversible capacity remained around 120 mAh g(-1)
      after 20 charge/discharge cycles. With improved cycling performance and very low
      cost, PDMcT could become a very promising cathode material when combined with a
      TEGDME-based electrolyte. The poor capacity in the carbonate-based electrolyte is
      a consequence of the irreversible reaction of the DMcT monomer and dimer with the
      solvent, emphasizing the importance of electrolyte chemistry when studying
      molecular-based battery materials.

PMID- 22644941
TI  - FimH antagonists: structure-activity and structure-property relationships for
      biphenyl alpha-D-mannopyranosides.
AB  - Urinary tract infections (UTIs) are caused primarily by uropathogenic Escherichia
      coli (UPEC), which encode filamentous surface-adhesive organelles called type 1
      pili. FimH is located at the tips of these pili. The initial attachment of UPEC
      to host cells is mediated by the interaction of the carbohydrate recognition
      domain (CRD) of FimH with oligomannosides on urothelial cells. Blocking these
      lectins with carbohydrates or analogues thereof prevents bacterial adhesion to
      host cells and therefore offers a potential therapeutic approach for prevention
      and/or treatment of UTIs. Although numerous FimH antagonists have been developed
      so far, few of them meet the requirement for clinical application due to poor
      pharmacokinetics. Additionally, the binding mode of an antagonist to the CRD of
      FimH can switch from an in-docking mode to an out-docking mode, depending on the
      structure of the antagonist. In this communication, biphenyl alpha-D-mannosides
      were modified to improve their binding affinity, to explore their binding mode,
      and to optimize their pharmacokinetic properties. The inhibitory potential of the
      FimH antagonists was measured in a cell-free competitive binding assay, a cell
      based flow cytometry assay, and by isothermal titration calorimetry. Furthermore,
      pharmacokinetic properties such as log D, solubility, and membrane permeation
      were analyzed. As a result, a structure-activity and structure-property
      relationships were established for a series of biphenyl alpha-D-mannosides.

PMID- 22644942
TI  - Angiotensin-(1-7) attenuates metastatic prostate cancer and reduces
      osteoclastogenesis.
AB  - BACKGROUND: Angiotensin-(1-7) [Ang-(1-7)] is an endogenous, heptapeptide hormone
      with anti-proliferative and anti-angiogenic properties. The primary objective of
      this study was to determine whether Ang-(1-7) effectively reduces prostate cancer
      metastasis in mice. METHODS: Human PC3 prostate cancer cells were injected into
      the aortic arch via the carotid artery of SCID mice pre-treated with Ang-(1-7) or
      injected into the tibia of athymic mice, administered Ang-(1-7) for 5 weeks
      beginning 2 weeks post-injection. Tumor growth and volume were determined by
      bioluminescent and magnetic resonance imaging. The presence of tumors was
      confirmed by hematoxylin and eosin staining; TRAP histochemistry was used to
      identify osteolytic lesions. The effect of Ang-(1-7) on osteoclastogenesis was
      assessed in differentiated bone marrow cells. RESULTS: Pre-treatment with Ang-(1
      7) prevented metastatic tumor formation following intra-aortic injection of PC3
      cells, while 83% of untreated mice developed tumors in metastatic sites.
      Circulating VEGF was significantly higher in control mice compared to mice
      administered Ang-(1-7). A 5-week regimen of the heptapeptide hormone attenuated
      intra-tibial tumor growth; Ang-(1-7) was significantly higher in the tibia of
      treated mice than in control animals. Osteoclastogenesis was reduced by 50% in
      bone marrow cells differentiated in the presence of Ang-(1-7), suggesting that
      the heptapeptide hormone prevents the formation of osteolytic lesions to reduce
      tumor survival in the bone microenvironment. CONCLUSIONS: These findings suggest
      that Ang-(1-7) may serve as an anti-angiogenic and anti-metastatic agent for
      advanced prostate cancer. By extension, the heptapeptide hormone may provide
      effective therapy for bone metastasis produced from primary tumors of the lung
      and breast.

PMID- 22644947
TI  - Physicochemical characterization of a prodrug of a radionuclide decorporation
      agent for oral delivery.
AB  - Intravenously administered calcium and zinc complexes of
      diethylenetriaminepentaacetic acid (DTPA) are the agents of choice to treat
      individuals who have been contaminated with radioactive actinides. However, their
      use in a mass casualty scenario is hampered by the need for trained personnel to
      receive treatment. Because DTPA is a highly ionized molecule with permeability
      limited bioavailability, the penta-ethyl ester prodrug of DTPA is under
      evaluation as an orally bioavailable radionuclide decorporation agent. In this
      work, the physicochemical properties of DTPA penta-ethyl ester were characterized
      to assess its potential for oral delivery. DTPA penta-ethyl ester was determined
      to be a low-viscosity liquid with Newtonian flow characteristics. Consistent with
      the measured pK(a) values, which range from 2.93 to 10.87, this prodrug exhibits
      pH-dependent solubility and lipophilicity properties that are representative of a
      weak base and favorable for oral absorption. It is miscible in solvents that are
      nonpolar to moderately polar and is sufficiently stable to avoid premature
      hydrolysis during gastrointestinal transit. Therapeutic effects were demonstrated
      in an initial efficacy study wherein oral treatments of the prodrug were given to
      rats contaminated with 241Am, providing preliminary indications of successful
      oral delivery. The properties of the prodrug indicate that it is conducive to
      oral delivery and may offer therapeutic benefits over the standard DTPA therapy
      following radionuclide contamination.

PMID- 22644949
TI  - Insights into molecular mechanisms contributing to individual susceptibility to
      steatohepatitis: lessons learned from mouse models.

PMID- 22644948
TI  - Fast fluorescence switching within hydrophilic supramolecular assemblies.
AB  - We designed a supramolecular strategy to modulate fluorescence in water under
      optical control. It is based on the entrapment of fluorophore-photochrome dyads
      within the hydrophobic interior of an amphiphilic polymer. The polymeric envelope
      around the dyads protects them from the aqueous environment, while imposing
      hydrophilic character on the overall supramolecular construct. In the resulting
      assemblies, the photochromic component can be operated reversibly on a
      microsecond timescale under the influence of ultraviolet stimulations. In turn,
      the reversible transformations control the emission intensity of the adjacent
      fluorophore. As a result, the fluorescence of such nanostructured constructs can
      be photomodulated for hundreds of cycles in water with microsecond switching
      speeds. Thus, our protocol for fast fluorescence switching in aqueous solutions
      can eventually lead to the realization of functional probes for the investigation
      of biological samples.

PMID- 22644950
TI  - Interconversion of metallabenzenes and cyclic eta2-allene-coordinated complexes.
AB  - Treatment of the osmabenzene [Os{CHC(PPh(3))CHC(PPh(3))CH}Cl(2)(PPh(3))(2)]Cl (1)
      with excess 8-hydroxyquinoline produces monosubstituted osmabenzene [Os{CH
      C(PPh(3))CHC(PPh(3))CH}(C(9)H(6)NO)Cl(PPh(3))]Cl (2) or disubstituted osmabenzene
      [Os{CHC(PPh(3))CHC(PPh(3))CH}(C(9)H(6)NO)(2)]Cl (3) under different reaction
      conditions. Osmabenzene 2 evolves into cyclic eta(2)-allene-coordinated complex
      [Os{CH=C(PPh(3))CH=(eta(2)-C=CH(2))}(C(9)H(6)NO)(PPh(3))(2)]Cl (4) in the
      presence of excess PPh(3) and NaOH, presumably involving a P-C bond cleavage of
      the metallacycle. Reaction of 4 with excess 8-hydroxyquinoline under air affords
      the S(N) Ar product [(C(9)H(6)NO)Os{CHC(PPh(3))CHCHC}(C(9)H(6)NO)(PPh(3))]Cl (5).
      Complex 4 is fairly reactive to a nucleophile in the presence of acid, which
      could react with water to give carbonyl complex
      [Os{CH=C(PPh(3))CH=CH(2)}(C(9)H(6)NO)(CO)(PPh(3))(2)]Cl (6). Complex 4 also
      reacts with PPh(3) in the presence of acid and results in a transformation to
      [Os{CHC(PPh(3))CHCHC}(C(9)H(6)NO)Cl(PPh(3))(2)]Cl (7) and
      [Os{CH=C(PPh(3))CH=(eta(2)-C=CH(PPh(3)))}(C(9)H(6)NO)Cl(PPh(3))]Cl (8). Further
      investigation shows that the ratio of 7 and 8 is highly dependent on the amount
      of the acid in the reaction.

PMID- 22644951
TI  - In vivo iontophoretic delivery of salmon calcitonin across microporated skin.
AB  - The purpose of this study was to determine the effect of microneedle (MN)
      technology and its combination with iontophoresis (ITP) on the in vivo
      transdermal delivery of salmon calcitonin (sCT). Maltose MNs (500 um) were used
      to porate skin prior to application of the drug, with or without ITP. Micropores
      created by maltose MNs were characterized by histological sectioning and calcein
      imaging studies, which indicated uniformity of the created micropores. In vivo
      studies were performed in hairless rats to assess the degree of enhancement
      achieved by ITP (0.2 mA/cm2 for 1 h), MNs (81 MNs), and their combination. In
      vivo studies indicate a serum maximal concentration of 0.61 +/- 0.42 ng/mL, 1.79
      +/- 0.72 ng/mL, and 5.51 +/- 0.32 ng/mL for ITP, MNs, and combination treatment,
      respectively. MN treatment alone increased serum concentration 2.5-fold and the
      combination treatment increased the concentration ninefold as compared with
      iontophoretic treatment alone. Combination treatment of ITP and MNs resulted in
      the highest delivery of sCT and therapeutic levels were achieved within 5 min of
      administration.

PMID- 22644952
TI  - Dehydration of highly concentrated solutions of fructose to 5
      hydroxymethylfurfural in a cheap and sustainable choline chloride/carbon dioxide
      system.
AB  - Fete DES sciences: The dehydration of fructose and inulin to HMF is conveniently
      performed in a cheap and sustainable choline chloride/CO(2) deep eutectic solvent
      (DES) system. The medium is capable of converting high contents of fructose (>100
      wt %) without affecting the yield of HMF (up to 72 %). The purity of the
      recovered HMF is >98%, and the reaction medium can be recycled.

PMID- 22644953
TI  - Metal-leachate-induced conjugate protein instability.
AB  - During the scale-up of an ultrafiltration/diafiltration (UF/DF) step for a
      protein-based conjugate vaccine, significant precipitation was observed at room
      temperature. It was found that a specific type of metal hosebarb fitting used in
      the UF/DF system, when placed in the conjugate solution, caused the
      precipitation. Inductively Coupled Plasma Mass Spectrometry analysis showed
      significant amounts of Ni(II), Zn(II), and Cu(II) present in the conjugate
      solution. A kinetic study showed that the concentration of these metal ions
      gradually increased with increasing incubation time with a corresponding decrease
      in conjugate concentration. Direct spiking of trace amounts of NiCl2, ZnCl2, and
      CuCl2 into the conjugate solution also caused precipitation, and spiking studies
      showed that the metal ions caused precipitation of the conjugate but not of the
      carrier protein, antigen, or carrier protein + linker. The precipitation was
      found to be significantly dependent on buffer species but not solution pH and led
      to an irreversible loss of tertiary structure even after dissolution in and
      removal of guanidine hydrochloride. The precipitation is likely the result of
      formation of transition-metal complexes with histidine residues on the antigen
      peptide, which may involve both intraconjugate and interconjugate antigens. Such
      complexation may lead to formation of multimers that may exceed the solubility
      limit.

PMID- 22644954
TI  - Once daily oral mesalamine compared to conventional dosing for induction and
      maintenance of remission in ulcerative colitis: a systematic review and meta
      analysis.
AB  - We systematically reviewed and compared the efficacy and safety of once daily
      (OD) mesalamine to conventional dosing for induction and maintenance of remission
      in ulcerative colitis (UC). A literature search to January 2012 identified all
      applicable randomized trials. Study quality was evaluated using the Cochrane risk
      of bias tool. The GRADE criteria were used to assess the overall quality of the
      evidence. Studies were subgrouped by formulation for meta-analysis. Eleven
      studies that evaluated 4070 patients were identified. The risk of bias was low
      for most factors, although five studies were single-blind and one was open-label.
      No difference was observed between the dosing strategies in the proportion of
      patients with clinical remission (relative risk [RR] 0.95; 95% confidence
      interval [CI] 0.82-1.10), clinical improvement (RR 0.87 95% CI 0.68-1.10), or
      relapse at 6 (RR 1.10; 95% CI 0.83-1.46) or 12 months (RR 0.92; 95% CI 0.83
      1.03). Subgroup analyses showed no important differences in efficacy. No
      significant difference was demonstrated in rates of medication adherence or
      adverse events between OD and conventional dosing. OD mesalamine appears to be as
      effective and safe as conventional dosing for both the treatment of mild to
      moderately active UC and for maintenance of remission in quiescent UC. The
      failure to demonstrate a superior rate of adherence to OD dosing may be due to
      the high rate of adherence observed in the clinical trials environment. Future
      research should assess the value of OD dosing in community settings.

PMID- 22644955
TI  - Shearing mechanics and the influence of a flexible symphysis during oral food
      processing in Sphenodon (Lepidosauria: Rhynchocephalia).
AB  - The New Zealand tuatara, Sphenodon, has a specialized feeding system in which the
      teeth of the lower jaw close between two upper tooth rows before sliding forward
      to slice food apart like a draw cut saw. This shearing action is unique amongst
      living amniotes but has been compared with the chewing power stroke of mammals.
      We investigated details of the jaw movement using multibody dynamics analysis of
      an anatomically accurate three-dimensional computer model constructed from
      computed tomography scans. The model predicts that a flexible symphysis is
      necessary for changes in the intermandibular angle that permits prooral movement.
      Models with the greatest symphysial flexibility allow the articulation surface of
      the articular to follow the quadrate cotyle with the least restriction, and
      suggest that shearing is accompanied by a long axis rotation of the lower jaws.
      This promotes precise point loading between the cutting edges of particular
      teeth, enhancing the effectiveness of the shearing action. Given that Sphenodon
      is a relatively inactive reptile, we suggest that the link between oral food
      processing and endothermy has been overstated. Food processing improves feeding
      efficiency, a consideration of particular importance when food availability is
      unpredictable. Although this feeding mechanism is today limited to Sphenodon, a
      survey of fossil rhynchocephalians suggests that it was once more widespread.

PMID- 22644956
TI  - Organ extracts and the development of psychiatry: hormonal treatments at the
      Maudsley Hospital 1923-1938.
AB  - The use of organ extracts to treat psychiatric disorder in the interwar period is
      an episode in the history of psychiatry which has largely been forgotten. An
      analysis of case-notes from The Maudsley Hospital from the period 1923-1938 shows
      that the prescription of extracts taken from animal testes, ovaries, thyroids,
      and other organs was widespread within this London Hospital. This article
      explores the way in which Maudsley doctors justified these treatments by tying
      together psychological theories of the unconscious with experimental data drawn
      from laboratory studies of human organs. It explores the logic behind these
      treatments and examines beliefs about their efficacy. The connection between this
      historical episode and current research in endocrinology and psychology is
      explored. 

PMID- 22644958
TI  - Conditioned medium from chondrocyte/scaffold constructs induced chondrogenic
      differentiation of bone marrow stromal cells.
AB  - For the application of bone marrow stromal cells (BMSCs) in cartilage tissue
      engineering, it is imperative to develop efficient strategies for their
      chondrogenic differentiation. In this study, the conditioned media derived from
      chondrocyte/scaffold constructs were used to direct chondrogenic differentiation
      of BMSCs. The porcine articular chondrocytes were seeded on the PGA/PLA scaffolds
      to form chondrocyte/scaffold constructs and were cultured to form engineered
      cartilage in vitro. The culture media were collected as conditioned media and
      used for chondrogenic induction of BMSC pellets (experimental group, Exp.). The
      chondrocyte pellets and BMSC pellets were cultured routinely as positive control
      (PC) and negative control (NC), respectively. After 4 weeks, the wet weight and
      GAG content in Exp. group and PC group were significantly higher than that in NC
      group. Histological and immunohistochemical analysis showed that cartilaginous
      tissue was formed with typical cartilage lacuna structure and positive staining
      of collagen Type II (Col II) in the peripheral area of the BMSC pellets in Exp.
      group. Gene expression of Sox9, Col II, and COMP in Exp. group and PC group were
      significantly higher than that in NC group. The growth factors in the conditioned
      media derived from human costal chondrocytes-scaffold constructs were tested by
      protein microassay. The conditioned media contained low levels of TGF-beta1,2,3,
      IGF-1 and high levels of IGF-2, FGF-4, and IGFBP4,6, and so forth. The soluble
      factors derived from the engineered cartilage can induce chondrogenic
      differentiation of BMSCs independently. Many cytokines may function in
      chondrogenesis in a coordinated way.

PMID- 22644957
TI  - Endocytoscopy allows accurate in vivo differentiation of mucosal inflammatory
      cells in IBD: a pilot study.
AB  - BACKGROUND: Precise activity assessment of inflammatory bowel disease (IBD) is
      essential to determine extent and severity of disease for optimized therapy.
      Despite ongoing developments in endoscopy, final diagnosis still relies on the
      interpretation of histopathological features. Recently, endocytoscopy (EC) was
      introduced as a new endoscopic imaging modality, enabling in vivo microscopic
      imaging within the mucosal layer of the gut at a magnification up to 1400-fold.
      The aim of our study was to determine the reliability of EC for the
      discrimination of mucosal inflammatory cells and intestinal inflammatory disease
      activity in patients with IBD. METHODS: In all, 40 patients with IBD (Crohn's
      disease n = 19; ulcerative colitis n = 21) who underwent colonoscopy were
      prospectively included in this study. Methylene blue or toluidine blue was
      topically applied to enable EC. Data were digitally saved and analyzed blinded to
      clinical and endoscopic data. RESULTS: EC enabled visualization of different
      histopathological features. Based on these specifications, it was possible to
      reliably distinguish single inflammatory cells by EC with the following
      respective sensitivities and specificities: neutrophilic (60% and 95%),
      basophilic (74.43% and 94.44%), eosinophilic granulocytes (75% and 90.48%), and
      lymphocytes (88.89% and 93.33%). Interobserver agreement between two
      investigators was substantial (kappa 0.61-0.78), while intraobserver agreement
      was substantial to almost perfect (kappa 0.76-0.88). Concordance between EC and
      histopathology for grading intestinal disease activity was 100%. CONCLUSIONS: EC
      enabled the detection and discrimination of single mucosal inflammatory cells and
      inflammatory disease activity. Therefore, this technique has the potential to
      improve both in vivo diagnosis and clinical management of IBD patients.

PMID- 22644959
TI  - Liver fibrosis in elderly cadavers: localization of collagen types I, III, and
      IV, alpha-smooth muscle actin, and elastic fibers.
AB  - We have shown a high prevalence of liver fibrosis in elderly cadavers with
      diverse causes of death by Sirius red stain; however, the various collagen types
      in these samples have yet to be evaluated. To further characterize the
      histopathology of the fibrotic lesions in the livers of these elderly cadavers,
      this study used immunohistochemistry and histochemistry to identify the principal
      collagens produced in liver fibrosis, fibrogenic cells and elastic fibers.
      Collagen I and III immunoreactions were found to colocalize in collagen fibers of
      fibrotic central veins, perisinusoidal fibrotic foci, portal tract stroma, and
      fibrous septa. alpha-Smooth muscle actin-expressing perisinusoidal hepatic
      stellate cells (HSCs), as well as perivenular, portal, and septal myofibroblasts,
      were closely associated with collagen fibers, reflecting their fibrogenic
      functions. HSCs and myofibroblasts were also noted to express collagen IV, which
      may contribute to production of basal lamina-like structures. In fibrotic livers,
      the sinusoidal lining showed variable immunostaining for collagen IV. Collagen IV
      immunostaining revealed vascular proliferation and atypical ductular reaction at
      the portal-septal parenchymal borders, as well as capillary-like vessels in the
      lobular parenchyma. While elastic fibers were absent in the space of Disse, they
      were found to codistribute with collagens in portal tracts, fibrous septa and
      central veins. Our combined assessment of collagen types, HSCs, myofibroblasts,
      and elastic fibers is significant in understanding the histopathology of fibrosis
      in the aging liver.

PMID- 22644960
TI  - Nonsteroidal anti-inflammatory drugs and the risk of skin cancer: a population
      based case-control study.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent the
      development of cancer by inhibiting cyclooxygenase (COX) enzymes, which are
      involved in carcinogenesis. Therefore, the authors of this report examined the
      association between NSAID use and the risk of squamous cell carcinoma (SCC),
      basal cell carcinoma (BCC), and malignant melanoma (MM). METHODS: From 1991
      through 2009, all incident cases of SCC (n = 1974), BCC (n = 13,316), and MM (n =
      3242) in northern Denmark were identified. Approximately 10 population controls
      (n = 178,655) were matched to each case by age, gender, and county of residence.
      The use of aspirin, other nonselective NSAIDs, or selective COX-2 inhibitors was
      ascertained through a prescription database. Conditional logistic regression
      analyses adjusted for potential confounders were used to compute odds ratios as
      estimates of incidence rate ratios (IRRs). RESULTS: For NSAIDs overall, ever use
      (>2 prescriptions) compared with nonuse (<=2 prescriptions) was associated with a
      decreased risk of SCC (IRR, 0.85; 95% confidence interval [CI], 0.76-0.94) and MM
      (IRR, 0.87; 95% CI, 0.80-0.95), especially for long-term use (>=7 years) and high
      intensity use (>25% prescription coverage during the total duration of use).
      NSAID use was not associated with a reduced risk of BCC overall (IRR, 0.97; 95%
      CI, 0.93-1.01), but the risk of BCC at sites other than the head and neck was
      reduced in association with long-term use (IRR, 0.85; 95% CI, 0.76-0.95) and high
      intensity use (IRR, 0.79; 95% CI, 0.69-0.91). All estimates of reduced risk were
      driven primarily by the use of nonselective NSAIDs and older COX-2 inhibitors
      (diclofenac, etodolac, and meloxicam). CONCLUSIONS: The current results indicated
      that NSAID use may decrease the risk of SCC and MM.

PMID- 22644961
TI  - p38 inhibitor SB203580 sensitizes the resveratrol-induced apoptosis in human lung
      adenocarcinoma (A549) cells.
AB  - Based on our recent findings that resveratrol, a natural plant polyphenol found
      in red grape skins as well as other food products, induces apoptosis via a
      caspase-independent intrinsic pathway in human lung adenocarcinoma cells, this
      study is designed to explore whether SB203580, a p38 inhibitor, potentiates the
      resveratrol-induced apoptosis of human lung adenocarcinoma (A549) cells. We found
      that pretreatment with SB203580 enhanced the resveratrol-induced apoptosis by
      accelerating the intrinsic apoptotic pathway including Bax activation, loss of
      mitochondrial membrane potential, and activation of both caspase-9 and -3.
      Although treatment with resveratrol alone did not induce caspase-8 activation,
      cotreatment with both SB203580 and resveratrol not only enhanced FasL cleavage
      but also activated caspase-8, indicating that the extrinsic apoptotic pathway may
      be involved in the synergistic effect. Collectively, we for the first time
      demonstrate that SB203580 synergistically enhances the resveratrol-induced
      apoptosis by accelerating Bax-mediated intrinsic pathway and initiating extrinsic
      pathway, suggesting a possible alternative therapeutic strategy for human lung
      cancer.

PMID- 22644962
TI  - Gut stem cells in tissue renewal and disease: methods, markers, and myths.
AB  - Homeostasis in adult tissue is maintained by the activity of a minor population
      of long-lived resident stem cells. These adult stem cells are defined by two
      essential attributes, self-renewal and multipotency, and their physiological
      activity is regulated by a specialized microenvironment, the stem cell niche.
      These adult stem cells are generally considered to divide infrequently, and cell
      expansion is mainly achieved through the rapid proliferation of transit
      amplifying progenitors before they undergo terminal differentiation. Organs that
      operate in abrasive environments, such as the mucosa of the skin, intestine, and
      stomach, display a higher tissue turnover rate, which consequently places them at
      higher risk of developing cancer. Indeed, colorectal cancer (CRC) is one of the
      most frequent cancers worldwide, with over a million new cases every year. Our
      understanding of stem cell function in tissue homeostasis and their potential
      role in cancer development has been greatly hampered by the lack of reliable
      specific biomarkers, but recent discoveries of membrane bound biomarkers promise
      great progress in the field. Here we review the current advances toward
      identifying the stem cells of the gastrointestinal tract and in understanding
      their microenvironmental regulation, and also discuss their implications for
      human cancer.

PMID- 22644963
TI  - Microbiological etiology and susceptibility of bacterial conjunctivitis isolates
      from clinical trials with ophthalmic, twice-daily besifloxacin.
AB  - INTRODUCTION: Bacterial conjunctivitis is a contagious infection of the surface
      of the eye usually treated empirically with topical antibiotics. Since the
      etiologic agent is rarely identified, it is important to monitor which bacteria
      cause conjunctivitis and determine their antibacterial resistance profiles.
      METHODS: A total of 496 bacterial samples were isolated during a randomized,
      double-masked, vehicle-controlled, parallel-group study conducted in the United
      States with besifloxacin ophthalmic suspension 0.6% dosed twice daily. Species
      were determined by standard biochemical and/or molecular identification methods.
      Minimum inhibitory concentrations were determined according to Clinical and
      Laboratory Standards Institute standards. RESULTS: The most prevalent species was
      Haemophilus influenzae, followed by Staphylococcus epidermidis, Staphylococcus
      aureus, the Streptococcus mitis group, and Streptococcus pneumoniae. One species
      identified in this study, which was not previously noted as a common cause of
      bacterial conjunctivitis, was Dolosigranulum pigrum. Ampicillin resistance was
      common among H. influenzae isolates, while macrolide resistance was high among S.
      pneumoniae, S. epidermidis, and S. aureus. The latter two species also included a
      number of isolates resistant to methicillin and ciprofloxacin. CONCLUSION:
      Antibiotic resistance among isolates remains a concern and the appearance of an
      emerging ocular pathogen, D. pigrum, suggests the need for continued observation.
      The topical ophthalmic fluoroquinolones continue to provide a good balance of low
      to moderate (i.e., manageable) levels of resistance plus broad-spectrum coverage
      for empiric treatment of ocular infections.

PMID- 22644964
TI  - Real-world use of Permixon(r) in benign prostatic hyperplasia--determining
      appropriate monotherapy and combination treatment.
AB  - INTRODUCTION: Benign prostatic hyperplasia (BPH) is a major health concern for
      aging men. The resulting lower urinary tract symptoms may have a profound effect
      on a patient's quality of life and it is recognized that patient acceptability of
      treatment is key to decreasing the human and economic burden of the condition.
      Alphaadrenergic antagonists (alpha-blockers), 5-alphareductase inhibitors (5
      ARIs), and phytotherapy as monotherapy or in combination, form the mainstay of
      medical treatment. METHODS: The Adelphi Permixon Study, a cross-sectional study
      of representative consulting patients with BPH in two European countries, was
      undertaken to examine the reasons for choice of medication. Physicians completed
      patient record forms, and data were analyzed for clinical outcomes and their
      relationship with the choice of appropriate therapy. RESULTS: Patients receiving
      combination therapies for BPH are likely to be older and are more likely to be
      retired than those on monotherapy. Combination therapy is adopted in the real
      world setting as first-line therapy on a not-infrequent basis. The analyses
      demonstrated an association between choice of Permixon(r) (Pierre Fabre
      Medicament, Castres, France) as appropriate monotherapy or in combination with
      alpha-blockers, and the following: BPH severity; treatment of general urinary
      symptoms, including storage and voiding symptoms; improvement of urinary flow
      rate; lack of a risk of sexual problems; and reduction of inflammation. Permixon
      combination with an alpha-blocker is associated with benefits in terms of speed
      of onset of action, reduction of inflammation, and a positive benefit regarding
      sexual problems when compared with use of alpha-blocker monotherapy. CONCLUSION:
      In the real clinical world, Permixon is considered an appropriate treatment for
      BPH as both monotherapy and in combination with alpha-blockers. Prescribing
      Permixon in combination with alpha-blockers can be demonstrated to provide
      benefits beyond use of either therapy alone.

PMID- 22644965
TI  - Pupil and salivary indicators of autonomic dysfunction in autism spectrum
      disorder.
AB  - Dysregulated tonic pupil size has been reported in autism spectrum disorder
      (ASD). Among the possible sources of this dysregulation are disruptions in the
      feedback loop between norepinephrine (NE) and hypothalamic systems. In the
      current study, we examined afternoon levels of salivary alpha-amylase (sAA, a
      putative correlate of NE) and cortisol (used to assess stress-based responses) in
      two independent samples of children with ASD. We found a larger pupil size and
      lower sAA levels in ASD, compared to typical and clinical age-matched controls.
      This was substantiated at the individual level, as sAA levels were strongly
      correlated with tonic pupil size. Relatively little diurnal variation in sAA
      taken in the home environment in the ASD group was also observed, while typical
      controls showed a significant linear increase throughout the day. Results are
      discussed in terms of potential early biomarkers and the elucidation of
      underlying neural dysfunction in ASD.

PMID- 22644966
TI  - The effect of augmented real-time image guidance on task workload during
      endoscopic sinus surgery.
AB  - BACKGROUND: Due to proximity to critical structures, the need for spatial
      awareness during endoscopic sinus surgery (ESS) is essential. We have developed
      an augmented, real-time image-guided surgery (ART-IGS) system that provides live
      navigational data and proximity alerts to the operating surgeon during ablation.
      We wished to test the hypothesis that task workload would be reduced when using
      this technology. METHODS: A trial involved 8 otolaryngology residents and fellows
      performing ESS on cadaveric specimens; 1 side in a conventional method (control)
      and 1 side with ART-IGS. After computed tomography scanning, anatomical
      contouring, and registration of the head, a three-dimensional (3D) virtual
      endoscopic view, ablative tool tracking, and proximity alerts were enabled. Each
      subject completed ESS tasks and rated their workload during and after the
      exercise using the National Aeronautics and Space Administration (NASA) Task Load
      Index (TLX). A questionnaire and open feedback interview were completed after the
      procedure. RESULTS: There was a significant reduction in mental demand, temporal
      demand, effort, and frustration when using the ART-IGS system in comparison to
      the control (p < 0.02). Perceived performance was increased (p = 0.02). Most
      subjects agreed that the system was sufficiently accurate, caused minimal
      interruption, and increased confidence. Optical tracking line-of-sight issues
      were frequently cited as the main limitation early in the study; however, this
      was largely resolved. CONCLUSION: ART-IGS reduces task workload for trainees
      performing ESS. Live navigation and alert zones may be a valuable intraoperative
      teaching aid.

PMID- 22644968
TI  - Taliglucerase alfa approved for Gaucher disease.

PMID- 22644969
TI  - IOM calls for consistent, rigorous approach to drug safety.

PMID- 22644967
TI  - Effects of exercise and environmental complexity on deficits in trace and
      contextual fear conditioning produced by neonatal alcohol exposure in rats.
AB  - In rodents, voluntary exercise and environmental complexity increases hippocampal
      neurogenesis and reverses spatial learning and long-term potentiation deficits in
      animals prenatally exposed to alcohol. The present experiment extended these
      findings to neonatal alcohol exposure and to delay, trace, and contextual fear
      conditioning. Rats were administered either 5.25 g/kg/day alcohol via gastric
      intubation or received sham-intubations (SI) between Postnatal Day (PD) 4 and 9
      followed by either free access to a running wheel on PD 30-41 and housing in a
      complex environment on PD 42-72 (wheel-running plus environmental complexity;
      WREC) or conventional social housing (SHSH) from PD 30 to 72. Adult rats (PD 80
      +/- 5) received 5 trials/day of a 10-s flashing-light conditioned stimulus (CS)
      paired with .8 mA footshock either immediately (delay conditioning) or after a 10
      s trace interval (trace conditioning) for 2 days. Neonatal alcohol exposure
      impaired context and trace conditioning, but not short-delay conditioning. The
      WREC intervention did not reverse these deficits, despite increasing context
      related freezing in ethanol-exposed and SI animals.

PMID- 22644970
TI  - Low-performing drug plans will be terminated from Medicare Part D.

PMID- 22644972
TI  - Financial impact of a pharmacist-managed clinic for long-acting injectable
      antipsychotics.

PMID- 22644973
TI  - Cost-effectiveness of rasburicase over i.v. allopurinol for treatment of tumor
      lysis syndrome.

PMID- 22644974
TI  - Strategies to improve impact of volunteer pharmacists in sub-Saharan Africa.

PMID- 22644975
TI  - Including emergency departments in hospitals' bar-code-assisted medication
      administration system.

PMID- 22644976
TI  - Improving appropriateness of initial i.v. acyclovir doses in a computerized
      prescriber-order-entry system.

PMID- 22644977
TI  - Pharmacist-prepared dispensing guidelines for drugs used in clinical research.

PMID- 22644978
TI  - Pharmacists' requirement for continuity of the clinical narrative in the
      electronic medical record.

PMID- 22644979
TI  - New developments in management of oral mucositis in patients with head and neck
      cancer or receiving targeted anticancer therapies.
AB  - PURPOSE: Issues surrounding the prevention and management of severe oral
      mucositis in patients with head and neck cancer and patients receiving targeted
      anticancer therapies are reviewed. SUMMARY: Cancer therapy-related mucositis is
      associated with many negative and potentially life-threatening sequelae. Patients
      receiving chemoradiotherapy for head and neck cancer are at high risk for severe
      oral mucositis, but there are currently no definitive recommendations on
      pharmacologic preventive strategies. Recently published evidence on the use of
      palifermin to combat oral mucositis during chemoradiotherapy for head and neck
      cancer is encouraging, with two randomized controlled trials indicating an
      absolute risk reduction of about 15%; however, palifermin use was not associated
      with lower rates of mucositis-related treatment delays or chemotherapy dosage
      reductions, and concerns about optimal dosage and cost-benefit issues persist.
      Oral mucositis due to targeted therapies for renal cell carcinoma and other
      disorders (e.g., kinase inhibitors, mammalian target of rapamycin inhibitors) is
      generally less severe than mucositis caused by conventional cytotoxic
      chemotherapy. For both types of mucositis, recommended management strategies
      include good oral hygiene and optimal pain control. Research in this area
      continues to be complicated by investigators' use of varying terminology and
      mucositis classification schemes. CONCLUSION: Palifermin appears to reduce the
      frequency of oral mucositis in patients treated for head and neck cancer, but its
      place in therapy has not been determined. Although the oral complications of
      targeted therapies are clinically distinct from those of conventional cytotoxic
      therapy, the literature recommends similar palliative management strategies for
      both.

PMID- 22644980
TI  - Risk of hypotension with concomitant use of calcium-channel blockers and
      macrolide antibiotics.
AB  - PURPOSE: The literature describing the risk of hypotension in patients receiving
      concomitant therapy with a calcium-channel blocker (CCB) and a macrolide
      antibiotic is reviewed. SUMMARY: A literature search was conducted to identify
      studies and reports describing significant drug interactions between CCBs and
      macrolide antibiotics resulting in hypotension. One retrospective clinical trial,
      one pharmacokinetics study, and five case reports were found using MEDLINE. While
      both dihydropyridine and nondihydropyridine CCBs are cytochrome P-450 isoenzyme
      3A4 (CYP3A4) substrates, verapamil was the CCB implicated in three of the five
      case reports. Based on currently available literature, it is unknown whether the
      risk of clinically significant hypotension is higher for patients receiving
      nondihydropyridine CCBs; however, due to the drugs' effects on the coronary
      arteries, there is the potential for more-serious cardiac complications with
      these agents. Both erythromycin and clarithromycin have been shown to prolong the
      Q-T interval, an effect that appears to increase when these drugs are given with
      CYP3A4 inhibitors. The potential for Q-T interval prolongation by both
      erythromycin and clarithromycin may increase the risk of clinically relevant
      hypotension and even shock in patients taking CCBs, in particular
      nondihydropyridines. CONCLUSION: Potentially significant hypotension and shock
      may occur when macrolide antibiotics, particularly erythromycin and
      clarithromycin, are administered concomitantly with CCBs. The frequency of
      hypotension as a result of concomitant CCB and macrolide administration appears
      to be small, but the risk of adverse effects and the severity of the effects
      appear to be greater for those patients who are older and in those with multiple
      comorbidities.

PMID- 22644981
TI  - Combination exenatide-sitagliptin therapy used with glipizide in a patient with
      type 2 diabetes mellitus.
AB  - PURPOSE: The case of a patient with type 2 diabetes mellitus who received
      combination exenatide-sitagliptin with glipizide is reported. SUMMARY: A 55-year
      old, 204-lb Caucasian woman arrived at a clinic with polydipsia. Her blood
      glucose concentration was 450 mg/dL and her glycosylated hemoglobin (HbA(1c))
      value was 13.4%. She was diagnosed with type 2 diabetes mellitus and started on
      metformin hydrochloride 500 mg orally twice daily. Metformin was later
      discontinued due to elevated liver function test values. Sitagliptin 100 mg daily
      was substituted, and glipizide was later added and its dosage adjusted over the
      next several months. After six months, her HbA(1c) value had decreased to 9.3%
      and she had gained 14 lb. Exenatide was then added to her regimen, and the dosage
      was adjusted to 10 MUg subcutaneously twice daily. Two months after the
      initiation of sitagliptin, glipizide, and exenatide, the patient had lost 10 lb,
      reported significant improvements in self-monitored blood glucose readings, and
      required a reduction in glipizide dosage despite no reported therapeutic
      lifestyle changes. Seven months after the initiation of exenatide, sitagliptin,
      and glipizide, her HbA(1c) value was 7.4%. Triple therapy resulted in a total
      HbA(1c) value reduction of 1.9%, a weight loss of 11 lb, and normalized liver
      function test values. The patient's high blood pressure was treated with losartan
      and remained at goal throughout the duration of this report. CONCLUSION: In a
      patient with type 2 diabetes mellitus, the addition of the incretin mimetic
      exenatide and the dipeptidyl peptidase-4 inhibitor sitagliptin to glipizide
      therapy appeared effective and safe.

PMID- 22644982
TI  - Possible case of nafcillin-induced acute interstitial nephritis.
AB  - PURPOSE: To report a case of acute interstitial nephritis (AIN) secondary to
      nafcillin. SUMMARY: A 55-year-old Hispanic man (height, 63 in.; weight, 61.2 kg)
      with a history of deep vein thrombosis in the right lower extremity,
      hypertension, hyperlipidemia, and hepatitis C infection was admitted to the
      hospital with right-sided chest pain that radiated down his right arm and leg.
      The patient was diagnosed with methicillin-sensitive Staphylococcus aureus
      endocarditis. A renal ultrasound was performed on hospital day 9 after the
      patient developed acute renal failure and showed diffusely increasing
      echogenicity of the renal parenchymal bilaterally with an interpolar cyst in the
      left kidney. A urine analysis, serum chemistry panels, and complete blood counts
      were consistent with AIN. The patient received a total of seven days of
      nafcillin, and cefazolin was initiated. A renal ultrasound and renal biopsy were
      performed, which confirmed the diagnosis of AIN. The patient received short-term
      hemodialysis, after which his renal function slowly returned to baseline. He then
      underwent an aortic valve replacement and tricuspid valve repair. His antibiotics
      were changed to rifampin and vancomycin after methicillin-resistant S. aureus was
      found in an aortic valve culture on hospital day 26. Cefazolin was discontinued 3
      days after rifampin and vancomycin were added. The patient received 18 more days
      of antibiotics and was discharged on the last day of therapy (hospital day 45).
      CONCLUSION: A 55-year-old, critically ill man developed a possible case of
      nafcillin-induced AIN after receiving a 7-day course of treatment with the drug.

PMID- 22644983
TI  - A novel collaborative practice model for treatment of mental illness in indigent
      and uninsured patients.
AB  - PURPOSE: The implementation and evaluation of a collaborative practice model
      (CPM) of mental health care at a free clinic are described. SUMMARY: Since 2004,
      the mental health clinic of the Cape Fear Clinic in Wilmington, NC, has provided
      pharmacotherapy and psychotherapy services to a mostly female population of poor
      and uninsured patients (average age, about 45 years) under a CPM that includes a
      state-licensed Clinical Pharmacist Practitioner with prescribing privileges.
      Spanish is the primary language of about 28% of the clinic's patients. At patient
      intake and (when possible) six months later, three measures of physical and
      mental health are administered: the Short-Form Health Survey (SF-12), the
      physical and mental component summaries of the Patient Health Questionnaire for
      depression (PHQ-9), and the Alcohol Use Disorders Identification Test (AUDIT);
      psychological counseling, psychotropic medications, and laboratory monitoring are
      provided as appropriate. In 2009, the clinic's volunteer health care providers
      served 56 patients (a total of 316 office visits), providing about 165 hours of
      free clinical services valued at more than $15,000 and free prescription
      medications valued at about $123,000. Although the clinic's experience has
      demonstrated the feasibility of CPM-based mental health care for the indigent and
      uninsured, a comparison of pretest and posttest data on a sample of clinic
      patients did not show significant changes from mean baseline SF-12, PHQ-9, and
      AUDIT scores, possibly due in large part to sampling challenges resulting from
      the loss of many clinic patients to follow-up. CONCLUSION: A CPM that includes a
      pharmacist with prescribing authority and psychologists was implemented to
      provide care for a low-income, uninsured, partly Spanish-speaking patient
      population.

PMID- 22644984
TI  - Patient-centered medical home: developing, expanding, and sustaining a role for
      pharmacists.
AB  - PURPOSE: The development of a patient-centered medical home (PCMH) health care
      model and the role of pharmacists in PCMHs at the University of Michigan are
      described. SUMMARY: In 2009, Blue Cross Blue Shield of Michigan (BCBSM) provided
      financial incentives to physician groups to implement PCMH principles. A
      partnership was formed among the department of pharmacy, college of pharmacy, and
      faculty group practice at the University of Michigan Health System (UMHS) to
      integrate clinical pharmacists into the PCMH model at eight general medicine
      practices. The rationale was that PCMH pharmacists could assist in managing
      chronic conditions by substituting or augmenting physician care, help achieve
      quality indicators, and increase revenue by billing for their services. At the
      University of Michigan, PCMH pharmacists currently provide direct patient care
      services at eight general medicine health centers for patients with diabetes,
      hypertension, hyperlipidemia, and polypharmacy, which are billable using T codes,
      which are payable to UMHS by most BCBSM plans. In the first year, the number of
      PCMH pharmacist half-day clinics varied from one to six per health center, and
      the mean number of patients per half-day clinic ranged from 2.2 to 6. Pharmacists
      in four PCMHs made more medication changes per visit than the other four,
      particularly for patients with diabetes. CONCLUSION: At the University of
      Michigan, PCMH pharmacists currently provide direct patient care services at
      eight general medicine health centers for patients with diabetes, hypertension,
      hyperlipidemia, and polypharmacy via referral from physicians.

PMID- 22644985
TI  - Developing entry-level competencies in sterile product preparation: an emerging
      challenge for pharmacy schools and experiential practice sites.
AB  - PURPOSE: Factors influencing the decision of hospital experiential sites to allow
      advanced pharmacy practice education (APPE) students to compound parenteral
      admixtures during their rotation experience were evaluated. METHODS: A survey was
      sent via e-mail to APPE sites used by Illinois Pharmacy Coalition schools in
      spring 2011. One preceptor from each site was identified to complete the survey.
      RESULTS: Of the 166 surveys delivered, 89 responses (53.6%) were obtained, and 1
      participant opted out. Forty respondents (45%) reported an average daily census
      of <= 100 patients. The majority of respondents (n = 49, 55%) had an average
      daily census of at least 100 patients. The majority of the reporting facilities
      (n = 38, 43%) were classified as community nonteaching hospitals. All of the
      practice sites had a cleanroom, a compounding aseptic isolator (glove box), or
      both. A total of 19 respondents (21%) indicated that their facilities did not
      permit APPE students to prepare sterile admixtures. Extensive training
      requirements established by hospitals was the most common reason cited for not
      allowing students to prepare admixtures (63%), followed by liability concerns
      (56%) and the cost and time associated with media-fill and glove fingertip
      testing (38% and 31%, respectively). CONCLUSION: The results of a survey of
      preceptors at a sample of APPE practice sites indicated that 21% did not allow
      pharmacy students to prepare sterile admixtures. Extensive training requirements,
      liability concerns, and the cost and time associated with media-fill and glove
      fingertip testing were cited as the most common reasons for not allowing students
      to prepare admixtures.

PMID- 22644986
TI  - Investing in our human resources.

PMID- 22644987
TI  - Three-dimensional turbo-spin-echo amide proton transfer MR imaging at 3-Tesla and
      its application to high-grade human brain tumors.
AB  - PURPOSE: Amide proton transfer (APT) imaging is able to extend the achievable
      magnetic resonance imaging (MRI) contrast to the protein level. In this study, we
      demonstrate the feasibility of applying a turbo-spin-echo (TSE)-based, three
      dimensional (3D) APT sequence into routine clinical practice for patients with
      brain tumors. PROCEDURES: Experiments were performed on a Philips 3-Tesla (3-T)
      MRI scanner using an eight-channel phased-array coil for reception. A fast 3D APT
      sequence with a TSE acquisition was proposed (saturation power, 2 MUT; saturation
      time, 500 ms; 8 slices). The gradient echo (GRE)-based field-mapping technique or
      water-saturation-shift-referencing (WASSR) technique was used to acquire B(0)
      maps to correct for B(0)-induced artifacts in APT images. The test was performed
      on a box of homogenous protein solution, four healthy volunteers, and eight
      patients with high-grade gliomas. RESULTS: The experimental data from a
      homogenous, protein-containing phantom and healthy volunteers show that the
      sequence produced a uniform contrast across all slices. The average MTR(asym)(3.5
      ppm) values with GRE B(0)-corrected 3D APT imaging and WASSR-corrected 3D APT
      imaging were both comparable to the values obtained using the undemanding single
      slice acquisition. The average APT image intensity was consistently higher in the
      tumor core than in the peripheral edema and in the contralateral normal-appearing
      white matter (both P < 0.001). CONCLUSION: 3D APT imaging of brain tumors can be
      performed in about 5 min at 3-T using a routine, commercial eight-channel SENSE
      coil.

PMID- 22644988
TI  - Reproducibility of static and dynamic (18)F-FDG, (18)F-FLT, and (18)F-FMISO
      MicroPET studies in a murine model of HER2+ breast cancer.
AB  - PURPOSE: The objective of this study is to determine the reproducibility of
      static 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG), 3'-deoxy-3'
      [(18)F]fluorothymidine ((18)F-FLT), and [(18)F]-fluoromisonidazole ((18)F-FMISO)
      microPET measurements, as well as kinetic parameters returned from analyses of
      dynamic (18)F-FLT and (18)F-FMISO data. PROCEDURES: HER2+ xenografts were
      established in nude mice. Dynamic data were acquired for 60 min, followed by a
      repeat injection and second scan 6 h later. Reproducibility was assessed for the
      percent-injected dose per gram (%ID/g) for each radiotracer, and with kinetic
      parameters (K (1) -k (4) , K ( i )) for (18)F-FLT and (18)F-FMISO. RESULTS: The
      value needed to reflect a change in tumor physiology is given by the 95 %
      confidence interval (CI), which is +/-14, +/-5, and +/-6 % for (18)F-FDG (n =
      12), (18)F-FLT (n = 11), and (18)F-FMISO (n = 11) %ID/g, respectively. V ( d )
      (=K (1) /k (2)), k (3), and K (FLT) are the most reproducible (18)F-FLT (n = 9)
      kinetic parameters, with 95 % CIs of +/-18, +/-10, and +/-18 %, respectively. V (
      d ) and K (FMISO) are the most reproducible (18)F-FMISO kinetic parameters (n =
      7) with 95 % CIs of +/-16 and +/-14 %, respectively. CONCLUSIONS: Percent
      injected dose per gram measurements are reproducible and appropriate for
      detecting treatment-induced changes. Kinetic parameters have larger threshold
      values, but are potentially sufficiently reproducible to detect treatment
      response.

PMID- 22644989
TI  - Heterozygous deletion of Atbf1 by the Cre-loxP system in mice causes preweaning
      mortality.
AB  - ATBF1 is a large nuclear protein that contains multiple zinc-finger motifs and
      four homeodomains. In mammals, ATBF1 regulates differentiation, and its mutation
      and/or downregulation is involved in tumorigenesis in several organs. To gain
      more insight into the physiological functions of ATBF1, we generated and
      validated a conditional allele of mouse Atbf1 in which exons 7 and 8 were flanked
      by loxP sites (Atbf1(flox) ). Germline deletion of a single Atbf1 allele was
      achieved by breeding to EIIa-cre transgenic mice, and Atbf1 heterozygous mice
      displayed reduced body weight, preweaning mortality, increased cell
      proliferation, and attenuated cytokeratin 18 expression, indicating
      haploinsufficiency of Atbf1. Floxed Atbf1 mice will help us understand such
      biological processes as neuronal differentiation and tumorigenesis.

PMID- 22644990
TI  - Association between weight status and depressive symptoms in adolescents: role of
      weight perception, weight concern, and dietary restraint.
AB  - Adolescence obesity and depression are increasingly prevalent and are associated
      with various health complications. The aim of this study was to examine the
      association between weight status (normal weight, overweight, and obese) and
      depressive symptoms in adolescents and to explore the probable mediators,
      including overweight perception, greater weight concern, and dietary restraint.
      During the period October 2010 to January 2011, we recruited 869 adolescents (47
      % girls; median age, 15.7 years) from four randomly selected high schools in
      Taipei city. The students were stratified into normal weight, overweight, or
      obese groups according to age- and gender-specific body mass index standards.
      Depressive symptoms were defined in students with a score of 29 or greater on the
      Center for Epidemiologic Studies Depression Scale. Overall, weight status was
      significantly associated with depressive symptoms (P = 0.02). Weight status was
      strongly associated with perceived overweight, greater weight concern, and
      dietary restraint. Those three variables were also associated with depressive
      symptoms. The association between overweight and depressive symptoms (odds ratio,
      2.23; 95 % confidence interval, 1.30-3.82) became weaker after controlling for
      perceived overweight, greater weight concern, and dietary restraint. The
      association between weight status and depressive symptoms in adolescents was
      partly mediated by perceived overweight, greater weight concern, and dietary
      restraint. Further prospective cohort studies are needed to explore the
      association between weight status and depressive symptoms.

PMID- 22644991
TI  - The clinical and genetic heterogeneity of mixed gonadal dysgenesis: does
      "disorders of sexual development (DSD)" classification based on new Chicago
      consensus cover all sex chromosome DSD?
AB  - Clinical findings illustrate the wide spectrum of the phenotypic manifestations
      of 45,X/46,XY mosaicism in the sex chromosome disorders of sex differentiation
      (DSD). The objective of study is to evaluate the characteristics of 45,X/46,XY
      patients and questioning of their place within the DSD categorization. The
      clinical findings of 11 patients with 45,X/46,XY mosaicism are described
      including the presentation, gonadal morphology, genital anatomy, and the hormone
      levels among 285 patients with DSD evaluated. Sixty-seven patients were diagnosed
      with sex chromosome DSD (50 Turner, three Klinefelter, ten 45,X/46,XY gonadal
      disgenesis, one 45X/46,XY ovotesticular DSD, one 47,XYY ovotesticular DSD, and
      two 46,XX/46,XY ovotesticular DSD). The type and the percentage of patients with
      45,X/46,XY mosaicism were as follows: Four cases of mix gonadal dysgenesis, four
      cases of partial gonadal dysgenesis, two cases of complete gonadal dysgenesis,
      one case of ovotesticular DSD. On the other hand, another patient that has
      45,X/46,XX mosaicism was diagnosed with MGD with the presence of the streak gonad
      on the right side and the testis on the other side. CONCLUSION: We suggest that
      sex chromosome DSD categorization can include 45,X/46,XY PGD and 45,X/46,XY CGD.
      Mixed gonadal dysgenesis may be also placed among the disorders of testicular
      differentiation of 46,XY DSD subdivision.

PMID- 22644992
TI  - The Sensory Gating Inventory as a potential diagnostic tool for attention-deficit
      hyperactivity disorder.
AB  - Diagnoses of attention-deficit hyperactivity disorder (ADHD) are often made
      rapidly in physicians' offices without thorough assessment. We examined whether
      adults diagnosed with ADHD would score differently from controls on a modified
      Sensory Gating Inventory (SGI: Hetrick et al. in Schizophr Bull 38:178-191, 2012;
      Kisley et al. in Psychophysiol 41:604-612, 2004), which would facilitate rapid
      and easy preliminary assessment of ADHD status. The modified SGI was administered
      to 22 controls and 22 adults with physician diagnoses of ADHD. Analysis was
      performed on the 17 SGI items and the three categories to which they belong
      (Perceptual Modulation, Distractibility, and Over-Inclusion). The Distractibility
      category, and its individual items, showed large group differences. In spite of a
      relatively small sample size, we found large effect sizes between those with and
      without ADHD diagnoses. The SGI is a simple, quick, paper/pencil method that may
      be used to facilitate accurate diagnosis of individuals experiencing ADHD
      symptoms, which may be especially useful when evaluations are made in settings
      such as physicians' offices.

PMID- 22644993
TI  - Isolated splenic metastasis from carcinoma of the breast: a case report.
AB  - Breast carcinoma with visceral metastasis to the lungs, liver, and bone is
      common. However, isolated splenic metastases from breast carcinoma are rare. This
      has been rarely described in the medical literature. This case report presents a
      48-year-old woman with newly diagnosed breast cancer and an isolated splenic
      metastasis diagnosed by ultrasound-guided fine-needle aspiration (FNA).
      Radiologic staging revealed no involvement of other organs, such as lungs, liver,
      or bone. The pathogenesis of rare single splenic metastasis and the diagnostic
      role of FNA on the spleen lesion are discussed. This case is being reported due
      to its rare metastatic initial presentation and the role of FNA in achieving the
      diagnosis.

PMID- 22644994
TI  - Neonatal handling induces deficits in infant mother preference and adult partner
      preference.
AB  - Neonatal handling is an experimental procedure used to understand how early-life
      adversity can negatively affect neurobehavioral development and place animals on
      a pathway to pathology. Decreased preference for the maternal odor during infancy
      is one of many behavioral deficits induced by neonatal handling. Here, we
      hypothesize that deficits in maternal odor preference may interfere with partner
      preference in the adult. To test this hypothesis, we assessed infant maternal
      odor preference and adult partner preference in different reproductive stages in
      both male and female rats that received neonatal handling. Our results indicate
      that only neonatally handled females present deficits in maternal odor preference
      during infancy, but both male and females present deficits in adult partner
      preference. However, sexual experience was effective in rescuing partner
      preference deficits in males. These results indicate that, considering infant and
      adult social interactions, females are more susceptible to the effects of
      neonatal handling than males.

PMID- 22644995
TI  - Self-powered ultrasensitive nanowire photodetector driven by a hybridized
      microbial fuel cell.
AB  - An integrated system consisting of a carbon fiber-ZnO hybrid nanowire (NW)
      multicolor photodetector is driven by a microbial fuel cell (see picture; PMMA =
      poly(methyl methacrylate), E = electrode). The self-powered photodetector can
      detect at light levels of as little as nW cm(-2) intensity with a responsivity of
      more than 300 A W(-1).

PMID- 22644996
TI  - Change in platelet levels during radiotherapy with concurrent and adjuvant
      temozolomide for the treatment of glioblastoma: a novel prognostic factor for
      survival.
AB  - BACKGROUND: Radiotherapy plus concomitant and adjuvant temozolomide (RCAT) is now
      standard treatment for grade IV glioblastoma (GBM). We report the results from
      our 7 years experience of using RCAT, and the potential role of a change in
      platelet count as a prognostic factor. METHODS: We identified all patients with
      biopsy-proven GBM who received RCAT at the Royal Free Hospital between 2002 and
      2009. We extracted data on demographic, tumour and treatment variables and
      overall survival and conducted univariate analyses on the association of the
      baseline factors with survival, and included those that were significant in a
      multivariate model. We then conducted exploratory analyses on the impact of
      changes in haematological parameters and overall survival. RESULTS: A total of
      eighty-four patients were included in the final analysis. Median overall survival
      in our study was 17.6 months. Overall survival rate at 1 year and 2 years were 70
      and 36 %, respectively. Platelet counts were seen to fall when measured from
      baseline to beginning of week 6. A decrease in platelet count from baseline to
      week 6 was associated with longer survival (p = 0.006), and this remains
      significant when adjusted for known prognostic factors. CONCLUSION: Our study
      shows the survival benefit seen in the phase III trial is reproducible in
      clinical practice. In addition, decreased platelet count during concurrent
      radiotherapy and temozolomide appears to correlate with prolonged survival, a
      finding that warrants further investigation.

PMID- 22644997
TI  - XPD Asp312Asn polymorphism is a risk factor for prostate cancer.
AB  - PURPOSE: The association between Asp312Asn and Lys751Gln polymorphisms of
      Xeroderma pigmentosum Group D (XPD) and prostate cancer risk are still
      inconclusive. For better understanding of the effects of these two polymorphisms
      on prostate cancer risk, a meta-analysis was performed. METHODS: An extensive
      search was performed to identify all case-control studies investigating such
      association. The strength of association between these two polymorphisms and
      prostate cancer risk was assessed by odds ratio (OR) with the corresponding 95 %
      confidence interval (95 % CI). RESULTS: A total of seven case-control studies
      were identified, among which five studies (1,257 cases and 1,956 controls) were
      eligible for Asp312Asn polymorphism and six studies (1,451 cases and 2,375
      controls) were eligible for Lys751Gln polymorphism. Asp312Asn polymorphism was
      associated with an increased risk of prostate cancer in additive and recessive
      genetic models (additive model: OR = 1.68, 95 % CI = 1.28-2.22, P = 0.00;
      recessive model: OR = 1.65, 95 % CI = 1.27-2.15, P = 0.00). In the subgroup
      analysis, Asp312Asn polymorphism was associated with an increased risk of
      prostate cancer among Asians in all three genetic models (additive model: OR =
      2.09, 95 % CI = 1.39-3.14, P = 0.00; dominant model: OR = 1.49, 95 % CI = 1.12
      1.98, P = 0.01; recessive model: OR = 1.93, 95 % CI = 1.31-2.83, P = 0.00).
      However, no significant associations were found between Lys751Gln polymorphism
      and prostate cancer risk in the overall analyses or the subgroup analyses by
      ethnicity. CONCLUSIONS: The results of this meta-analysis indicate that the XPD
      Asp312Asn polymorphism is a risk factor for prostate cancer development.

PMID- 22644998
TI  - Highlighting nuclear membrane staining in thyroid neoplasms with emerin: review
      and diagnostic utility.
AB  - Immunohistochemical staining (IHC) with emerin, an integral inner nuclear
      membrane protein, highlights nuclear membrane details in papillary thyroid
      carcinoma (PTC). We evaluated emerin for highlighting nuclear shape, grooves,
      inclusions, circumferential nuclear membrane irregularities ("garlands"), deep
      "stellate" membrane invaginations, and crescents in 34 fine-needle aspiration
      (FNA) cell blocks, PTC (n = 24) and follicular neoplasms (FN) (n = 10). Tissue
      microarrays were also examined for 182 cases, PTC (n = 95) and non-PTC (n = 87).
      Emerin IHC of PTC revealed a predominantly oval nuclear shape in the majority of
      cases, with FN demonstrating round nuclei and FV of PTC showing a roughly equal
      distribution of round and oval shapes. In addition to oval nuclear shape, the
      presence of emerin-positive nuclear grooves, circumferential emerin nuclear
      "garlands," nuclear crescent shapes, and chromatin clearing on cell block H&E
      staining were significant predictors of PTC by regression analysis. Emerin IHC of
      thyroid FNA and surgical specimens serves as a useful adjunct to conventional H&E
      staining in the diagnosis of PTC and its distinction from FN by delineating
      diagnostic nuclear membrane irregularities ("garlands" and crescents), nuclear
      grooves, and a characteristic oval nuclear shape. In diagnostically challenging
      cases with limited cellularity, emerin staining can help to provide a more
      definitive diagnosis of PTC.

PMID- 22644999
TI  - Clinical cardiology consultation at non-cardiology departments: stepchild of
      patient care?
AB  - BACKGROUND: Although patient care in cardiology departments may be of high
      quality, patients with cardiac disease in other departments tend to receive less
      attention from cardiologists. Driven by the shorter duration of admission
      nowadays and the fact that consultations are often performed in between the daily
      work schedules, the amount of cardiac disease as well as the impact on the daily
      workload can be underestimated. We determined characteristics, prevalence of
      cardiac disease and in-hospital mortality of patients in whom cardiology
      consultation was requested. METHOD: In this prospective, observational study,
      individual data of all consecutive patients admitted to non-cardiology
      departments in whom cardiology consultation was requested were registered.
      RESULTS: During the study period, 264 patients were included. Mean age was 70
      years. Most patients were admitted to the internal medicine ward (37 %), followed
      by the surgical ward (30 %). The most common reasons for cardiology consultation
      were: suspected heart failure (20 %), suspected infective endocarditis (15 %),
      suspected rhythm abnormalities (14 %) and suspected acute coronary syndrome (13
      %). In 29 % of all consultations a cardiac diagnosis was found. Hospital
      mortality was 9.0 %. CONCLUSION: Patients who are admitted to a non-cardiology
      department and who need cardiology consultation are particularly elderly people
      with a high prevalence of cardiac disease and high in-hospital mortality. For
      these reasons cardiology consultation is an important part of clinical cardiology
      deserving a structured approach.

PMID- 22645000
TI  - Coupled beats in a boogie dance duet. What is the mechanism?

PMID- 22645001
TI  - Coupled beats in a boogie dance duet. What is the mechanism?

PMID- 22645002
TI  - Hepatitis E virus: neutralizing sites, diagnosis, and protective immunity.
AB  - There have been increased attentions on HEV and its associated diseases in recent
      years as a result of an increased number of reports on autochthonous patients
      from many developed countries. Vaccine development and better disease management
      are expected from protective immunity with increased knowledge on the
      pathogenesis and virology of HEV. This review summarizes the current
      understanding of the HEV virology, the key neutralization sites (epitopes) on the
      surface of the viral capsid, the host humoral immune responses for HEV infection,
      and the protective immunity conferred by natural infection and vaccination.
      Recombinant VLPs were prepared to mimic the protective and neutralizing epitopes
      on the virion surface, thus being capable of eliciting protective immunity when
      injected to nonhuman primates or human volunteers during preclinical tests and
      clinical trials. Four markers-viral RNA, anti-HEV IgM, anti-HEV IgG, and low
      avidity of anti-HEV IgG-are important in the diagnosis of HEV infection,
      particularly for patients presenting with acute hepatitis symptoms. This toolbox
      of genomic and immunological assays is valuable in furthering our understanding
      of the time course of HEV infection and the subsequent hepatitis during
      preclinical and clinical development of an efficacious vaccine. Two vaccine
      candidates had shown good tolerability, high immunogenicity, and high efficacy
      against symptomatic and/or asymptomatic HEV infection. One of them has been
      licensed in China recently. However, many issues need to be resolved before new
      technological progresses can benefit the people who need them most.

PMID- 22645003
TI  - Kinetics and equilibrium properties of the biosorption of Cu2+ by algae.
AB  - The purpose of this study was to examine the kinetics and equilibrium properties
      of freshwater algae with Cu(2+). This was a model system to explore using algae
      as biosensors for water quality. Methods included making luminescence
      measurements (fluorescence) and copper ion-selective electrode (CuISE)
      measurements vs. time to obtain kinetic data. Results were analyzed using a
      pseudo-first-order model to calculate the rate constants of Cu(2+) uptake by
      algae: k (p(Cu-algae)) = 0.0025 +/- 0.0006 s(-1) by CuISE and k (p(Cu-algae)) =
      0.0034 +/- 0.0011 s(-1) by luminescence. The binding constant of Cu-algae, K (Cu
      algae), was 1.62 +/- 0.07 * 10(7) M(-1). Fluorescence results analyzed using the
      Stern-Volmer relationship indicate that algae have two types of binding sites of
      which only one appears to affect quenching. The fluorescence-based method was
      found to be able to detect the reaction of algae with Cu(2+) quickly and at a
      detection limit of 0.1 mg L(-1).

PMID- 22645004
TI  - Responses of earthworm to aluminum toxicity in latosol.
AB  - Excess aluminum (Al) in soils due to acid rain leaching is toxic to water
      resources and harmful to soil organisms and plants. This study investigated
      adverse impacts of Al levels upon earthworms (Eisenia fetida) from the latosol
      (acidic red soil). Laboratory experiments were performed to examine the survival
      and avoidance of earthworms from high Al concentrations and investigate the
      response of earthworms upon Al toxicity at seven different Al concentrations that
      ranged from 0 to 300 mg kg(-1) over a 28-day period. Our study showed that the
      rate of the earthworm survival was 100 % within the first 7 days and decreased as
      time elapsed, especially for the Al concentrations at 200 and 300 mg kg(-1). A
      very good linear correlation existed between the earthworm avoidance and the soil
      Al concentration. There was no Al toxicity to earthworms with the Al
      concentration <= 50 mg kg(-1), and the toxicity started with the Al concentration
      >= 100 mg kg(-1). Low Al concentration (i.e., <50 mg kg(-1)) enhanced the growth
      of the earthworms, while high Al concentration (>100 mg kg(-1)) retarded the
      growth of the earthworms. The weight of earthworms and the uptake of Al by
      earthworms increased with the Al concentrations from 0 to 50 mg kg(-1) and
      decreased with the Al concentrations from 50 to 300 mg kg(-1). The protein
      content in the earthworms decreased with the Al concentrations from 0 to 100 mg
      kg(-1) and increased from 100 to 300 mg kg(-1). In contrast, the catalase (CAT)
      and superoxide dismutase (SOD) activities in the earthworms increased with the Al
      concentrations from 0 to 100 mg kg(-1) and decreased from 100 to 300 mg kg(-1).
      The highest CAT and SOD activities and lowest protein content were found at the
      Al concentration of 100 mg kg(-1). Results suggest that a high level of Al
      content in latosol was harmful to earthworms.

PMID- 22645006
TI  - Invertebrates control metal/metalloid sequestration and the quality of DOC/DON
      released during litter decay in slightly acidic environments.
AB  - Plant litter and organic sediments are a main sink for metals and metalloids in
      aquatic ecosystems. The effect of invertebrate shredder (a key species in litter
      decay) on metal/metalloid fixation by organic matter is described only under
      alkaline water conditions whereas for slightly acidic waters nothing can be
      found. Furthermore, less is known about the effect of invertebrate shredders on
      the quality of dissolved organic carbon (DOC) and nitrogen (DON) released during
      litter decay. We conducted an experiment to investigate the impact of
      invertebrate shredder (Gammarus pulex) on metal/metalloid fixation/remobilization
      and on the quality of DOC/DON released under slightly acidic water conditions.
      During decomposition of leaf litter, invertebrate shredder facilitated
      significantly the emergence of smaller particle sizes of organic matter. The
      capacity of metal fixation was significantly higher in smaller particles (POM
      2,000-63 MUm) compared to original leaf litter and litter residues. Thus, G.
      pulex enhanced metal fixation by organic partition of sediments by increasing the
      amount of smaller particle of organic matter in aquatic ecosystems. In contrast,
      the capacity of metal/metalloid fixation in the smallest fraction of POM (<63
      MUm) was lower compared with leaf residues in treatment without invertebrates.
      Remobilization of metals and metalloids was very low for all measured elements. A
      significant effect of invertebrates on quantitative formation of DOC/DON was
      confirmed. The quality of released DOC/DON, which may affect metal/metalloid
      remobilization, was also significantly affected by invertebrate shredders (e.g.,
      more carboxylates). Hence, invertebrate shredder enhanced significantly the
      fixation of metals/metalloids into POM in slightly acidic environments.

PMID- 22645005
TI  - Behaviour and variability of local and regional oxidant levels (OX = O3 + NO2)
      measured in a polluted area in central-southern of Iberian Peninsula.
AB  - The purpose of this work is to contribute to the understanding of the
      photochemical air pollution in central-southern of the Iberian Peninsula,
      analysing the behaviour and variability of oxidant levels (OX = O(3) + NO(2)),
      measured in a polluted area with the highest concentration of heavy industry in
      central Spain. A detailed air pollution database was observed from two monitoring
      stations. The data period used was 2008 and 2009, around 210,000 data, selected
      for its pollution and meteorological statistics, which are very representative of
      the region. Data were collected every 15 min, however hourly values were used to
      analyse the seasonal and daily ozone, NO, NO(2) and OX cycles. The variation of
      OX concentrations with NO(x) is investigated, for the first time, in the centre
      of the Iberian Peninsula. The concentration of OX was calculated using the sum of
      a NO(x)-independent 'regional' contribution (i.e. the O(3) background), and a
      linearly NO(x)-dependent 'local' contribution. Monthly dependence of regional and
      local OX concentration was observed to determine when the maximum values may be
      expected. The variation of OX concentrations with levels of NO(x) was also
      measured, in order to pinpoint the atmospheric sources of OX in the polluted
      areas. The ratios [NO(2)]/[OX] and [NO(2)]/[NO(x)] vs. [NO(x)] were analysed to
      find the fraction of OX in the form of NO(2), and the possible source of the
      local NO(x)-dependent contribution, respectively. The progressive increase of the
      ratio [NO(2)]/[OX] with [NO(x)] observed shows a greater proportion of OX in the
      form of NO(2) as the level of NO( x ) increases. The higher measured values in
      the ratio [NO(2)]/[NO(x)] should not be attributed to NO(x) emissions by
      vehicles; they could be explained by industrial emission, termolecular reactions
      or formaldehyde and HONO directly emitted by vehicles exhausts. We also estimate
      the rate of NO(2) photolysis, J (NO(2)) = 0.18-0.64 min(-1), a key atmospheric
      reaction that influence O(3) production and then the regional air quality. The
      first surface plot study of annual variation of the daily mean oxidant levels,
      obtained for this polluted area may be used to improve the atmospheric
      photochemical dynamic in this region of the Iberian Peninsula where there are
      undeniable air quality problems.

PMID- 22645007
TI  - Coupling of solar-assisted advanced oxidative and biological treatment for
      degradation of agro-residue-based soda bleaching effluent.
AB  - This study evaluates the effect of integrated solar-assisted advanced oxidation
      process (AOP) and biological treatment on the extent of degradation of effluents
      from chlorination (C) and first alkaline extraction (E(1)) stages of soda pulp
      bleaching in agro-residue-based pulp and paper mill. Biodegradation of the
      effluents was attempted in suspended mode using activated sludge from the
      functional pulp and paper industry effluent treatment plant acclimatized to
      effluents in question. The photocatalytic treatment was employed using zinc oxide
      (ZnO) in slurry mode for decontamination of effluents in a batch manner and the
      degradation was evaluated in terms of reduction in chemical oxygen demand. The
      biological treatment (24 h) of C and E(1) effluent resulted in 30 and 57 % of
      degradation, respectively. Solar-induced AOP of C and E(1) effluents resulted in
      53 and 43 % degradation under optimized conditions (2.5 g L(-1) ZnO at pH 8.0)
      after 6 h of exposure. For C effluent, a short duration of solar/ZnO (1 h) prior
      to biological treatment reduced the time required at biological step from 24 to
      12 h for almost same extent (92 %) of degradation. However, sequential biological
      treatment (24 h) followed by solar/ZnO (2 h) resulted in 85.5 % degradation. In
      contrast, in the case of E(1) effluent, sequential biological (24 h)-solar/ZnO (2
      h) system effectively degrades effluent to 95.4 % as compared to 84.8 %
      degradation achieved in solar/ZnO (2 h)-biological treatment (24 h) system. In
      the present study, the sequencing of photocatalysis with the biological treatment
      is observably efficient and technically viable process for the complete
      mineralization of the effluents.

PMID- 22645008
TI  - Multiparametric approach for assessing environmental quality variations in West
      African aquatic ecosystems using the black-chinned tilapia (Sarotherodon
      melanotheron) as a sentinel species.
AB  - The study highlights the potential of the black-chinned tilapia to be used as a
      sentinel to assess environmental contaminants based on the use of a set of
      biomarkers. The usefulness of fish species as sentinels for assessing aquatic
      environment contamination was tested using a set of biomarkers in Senegalese
      environments characterized by multi-pollution sources. The black-chinned tilapia
      (Sarotherodon melanotheron) was selected as a sentinel because of its abundance,
      wide distribution in all coastal aquatic ecosystems and physiological properties.
      The potential influence of confounding factors such as salinity on biomarker in
      the tilapia has been examined. Individuals were sampled during two seasons (dry
      and wet) in eight sites characterized by various degrees of anthropogenic
      contamination and different salinities (from 0 to 102 psu). Biomarkers-including
      growth rate (GR), condition factor (CF), biotransformation enzymes such as 7
      ethoxyresorufin-O-deethylase (EROD) and glutathione-S-transferase (GST), lipid
      peroxidation (TBARS) and acetylcholinesterase (AChE)-were measured. Chemical
      contaminant [polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls
      (PCBs) and organochlorine pesticides (OCPs)] levels showed different sources of
      contamination with relatively high concentrations of PAHs in the Hann Bay and
      Foundiougne locations. The most sensitive biomarker present in different sites
      according to the principal component analysis is EROD. Few variations of the AChE
      activity and TBARS levels were found. No clear relationship was found between
      biomarker responses and salinity, but GR and CF were lower in hypersaline
      conditions. Tilapia is responsive to environmental contaminants such as PAHs,
      OCPs and PCBs. The S. melanotheron multiparametric approach showed a better
      discrimination of sites.

PMID- 22645009
TI  - Response surface modelling of Cr6+ adsorption from aqueous solution by neem bark
      powder: Box-Behnken experimental approach.
AB  - The main aim of this study is to investigate the combined effect of different
      operating parameters like adsorbent dose, initial Cr(6+) concentration and pH on
      the removal of Cr(6+) from aqueous solution using neem bark powder (NBP). A
      series of batch experiments were performed to find out the adsorption isotherms
      and kinetic behaviour of Cr(6+) in the aqueous solution. The adsorption process
      was examined with three independent variables viz. NBP dosage, initial Cr(6+)
      concentrations and pH. Seventeen batch experiments designed by Box-Behnken using
      response surface methodology were carried out, and the adsorption efficiency was
      modelled using polynomial equation as the function of the independent variables.
      Based on the uptake capacity and economic use of adsorbent, the independent
      variables were optimized by two procedures. The desirability of first and second
      optimization procedures were found to be 1.00 and 0.84, respectively, which shows
      that the estimated function may well represent the experimental model. The
      kinetic study indicated that the rate of adsorption confirms to the pseudo-second
      order rate equation. Thermodynamics study indicated that the adsorption process
      was spontaneous and endothermic in nature. The surface texture changes in NBP
      were obtained from FT-IR analysis. The optimized result obtained from RAMP plots
      revealed that the NBP was supposed to be an effective and economically feasible
      adsorbent for the removal of Cr(6+) from an aqueous system.

PMID- 22645010
TI  - Laboratory assessment of uptake and toxicity of lanthanum (La) in the leaves of
      Hydrocharis dubia (Bl.) Backer.
AB  - Increasing amounts of lanthanum (La) is released into aquatic environments.
      However, little information is available on the influence of La on aquatic
      plants. In this study, physiological and ultrastructural responses of Hydrocharis
      dubia (Bl.) Backer leaves to elevated concentrations of La (up to 160 MUM) were
      investigated. The accumulation of La was found to be increased in a concentration
      dependent manner. La disturbed the intrinsic balance of nutrient elements (P, Mg,
      Ca, Fe, K, and Zn). Pigment content decreased with the rise of the La
      concentrations and the EC(50) value for chlorophyll was 20 MUM on day 7. The
      antioxidants (superoxide dismutase, peroxidase, catalase, reduced ascorbate, and
      reduced glutathione) exhibited varied response to the La treatments.
      Malondialdehyde content enhanced gradually at all La concentrations. The
      enhancement in proline content was found in a concentration-dependent manner. The
      amounts of three polypeptides with apparent molecular weights of 61.9, 51.5, and
      16.7 kDa, respectively, were gradually diminished, as well as one existing
      polypeptides with apparent molecular weight of 22.3 kDa, elevating in response to
      increasing La concentrations. Significant damage to the chloroplast,
      mitochondrion, and nucleus was imposed by La indicated a general disarray in the
      cellular functions. The negative effects of La on H. dubia unequivocally indicate
      that La could exert an adverse influence on aquatic ecosystem and should lead to
      a more careful discharge of such elements into water environment.

PMID- 22645011
TI  - Performance evaluation and application of surface-molecular-imprinted polymer
      modified TiO2 nanotubes for the removal of estrogenic chemicals from secondary
      effluents.
AB  - The removal of estrogenic chemicals during wastewater reclamation has been a
      great concern. Current advanced treatment processes are inefficient for the
      removal of estrogenic chemicals from secondary effluents of municipal wastewater
      treatment plants (WWTPs) due to the coexistence of other pollutants with less
      environmental significance which are also removed simultaneously. The search for
      highly selective and low-cost removal methods is warranted. Therefore, surface
      molecular-imprinted polymer-modified TiO(2) nanotube (S-MIP-TiO(2) NT)
      photocatalysts were fabricated, characterized, and tested for the removal of
      estrogenic pollutants from wastewater in this study for the first time. Scanning
      electron microscopy and Fourier-transform infrared spectroscopy studies showed
      that the TiO(2) NTs (with an average diameter of 60 nm) were successfully
      imprinted with functional groups (i.e., carboxyl). The adsorption selectivity and
      photocatalytic activity of the S-MIP-TiO(2) NTs towards template compound (17beta
      estradiol, E2) were improved, compared with neat TiO(2) NTs. Interestingly, S-MIP
      TiO(2) NTs exhibited higher adsorption intensity and photocatalytic selectivity
      at low concentrations (from 10 ng/L to 100 MUg/L, as normal estrogenic chemical
      concentrations in secondary effluents) of E2 than that at high concentrations
      (from 10 to 1,000 mg/L). It was also found that some representative estrogenic
      chemicals and estrogenic activity could be selectively and rapidly removed from
      secondary effluents of municipal wastewater treatment plants using S-MIP-TiO(2)
      NTs as photocatalysts. In addition, S-MIP-TiO(2) NT photocatalysts exhibited
      excellent regeneration characteristics. Photocatalytic treatment using S-MIP
      TiO(2) NTs could be a promising approach for the effective removal of estrogenic
      chemicals from secondary effluents of municipal WWTPs.

PMID- 22645012
TI  - Removal of Pb(II), Cd(II), Cu(II), and Zn(II) by hematite nanoparticles: effect
      of sorbent concentration, pH, temperature, and exhaustion.
AB  - Nanoparticles offer the potential to improve environmental treatment technologies
      due to their unique properties. Adsorption of metal ions (Pb(II), Cd(II), Cu(II),
      Zn(II)) to nanohematite was examined as a function of sorbent concentration, pH,
      temperature, and exhaustion. Adsorption experiments were conducted with 0.05,
      0.1, and 0.5 g/L nanoparticles in a pH 8 solution and in spiked San Antonio tap
      water. The adsorption data showed the ability of nanohematite to remove Pb, Cd,
      Cu, and Zn species from solution with adsorption increasing as the nanoparticle
      concentration increased. At 0.5 g/L nanohematite, 100 % Pb species adsorbed, 94 %
      Cd species adsorbed, 89 % Cu species adsorbed and 100 % Zn species adsorbed.
      Adsorption kinetics for all metals tested was described by a pseudo second-order
      rate equation with lead having the fastest rate of adsorption. The effect of
      temperature on adsorption showed that Pb(II), Cu(II), and Cd(II) underwent an
      endothermic reaction, while Zn(II) underwent an exothermic reaction. The
      nanoparticles were able to simultaneously remove multiple metals species (Zn, Cd,
      Pb, and Cu) from both a pH 8 solution and spiked San Antonio tap water.
      Exhaustion experiments showed that at pH 8, exhaustion did not occur for the
      nanoparticles but adsorption does decrease for Cd, Cu, and Zn species but not Pb
      species. The strong adsorption coupled with the ability to simultaneously remove
      multiple metal ions offers a potential remediation method for the removal of
      metals from water.

PMID- 22645013
TI  - Biodegradation kinetics of phenanthrene by a fusant strain.
AB  - The fusant strain (F14), which produced by protoplast fusion between Sphingomonas
      sp. GY2B (GenBank DQ139343) and Pseudomonas sp. GP3A (GenBank EU233280), was
      tested for phenanthrene biodegradation at 30  degrees C and pH of 7.0. The
      kinetics of phenanthrene biodegradation by F14 was investigated over a wide range
      of initial concentration (15-1,000 mg l(-1)). The rate and the extent of
      phenanthrene degradation increased with the increase of concentration up to 230
      mg l(-1), which indicated negligible inhibition effect at low concentrations. The
      non-competitive inhibition model was found to be fit for the process. GC-MS
      analysis showed that biodegradation of phenanthrene by F14 was via dioxygenation
      at both 1,2- and 3,4-positions and followed by 2-hydroxy-1-naphthoic acid and 1
      hydroxy-2-naphthoic acid. The relative intensity of 2-hydroxy-1-naphthoic acid
      was approximately 3-4 times higher than that of 1-hydroxy-2-naphthoic acid,
      indicating the 2-hydroxy-1-naphthoic acid was the predominant product in the
      phenanthrene degradation by fusant strain F14.

PMID- 22645014
TI  - Characterization of a newly isolated highly effective 3,5,6-trichloro-2-pyridinol
      degrading strain Cupriavidus pauculus P2.
AB  - A bacterial strain P2 capable of degrading 3,5,6-trichloro-2-pyridinol (TCP) was
      isolated and characterized. Phylogenetic analysis based on 16S rRNA gene sequence
      indicated that it belonged to the genus of Cupriavidus, because it showed the
      highest sequence similarity to Cupriavidus pauculus LMG 3413(T) (99.7 %) and DNA
      DNA relatedness value between strain P2 and C. pauculus LMG 3413(T) was 76.8 %.
      In combination with morphological, physiological and biochemical characters,
      strain P2 was identified as C. pauculus. It could use TCP as the sole carbon
      source and energy source for its growth. It showed a high average degradation
      rate of 10 mg/L h in mineral salt medium amended with TCP (50-800 mg/L). During
      TCP degradation, chloridion was released into the medium in two obvious
      discontinuous stages. Along with this, two colorful metabolites were produced.
      Finally, the molarity of the total released chloridion was three times that of
      the initial TCP in the medium. This is the first report of TCP-degrading strain
      from the genus of Cupriavidus and the detection of two colorful metabolites
      during TCP degradation. Strain P2 might be a promising candidate for its
      application in the bioremediation of TCP-polluted environments.

PMID- 22645015
TI  - Effects of xylitol on xylitol-sensitive versus xylitol-resistant Streptococcus
      mutans strains in a three-species in vitro biofilm.
AB  - We studied the effects of xylitol on biofilms containing xylitol-resistant (Xr)
      and xylitol-sensitive (Xs) Streptococcus mutans, Actinomyces naeslundii and S.
      sanguinis. The biofilms were grown for 8 and 24 h on hydroxyapatite discs. The
      viable microorganisms were determined by plate culturing techniques and
      fluorescence in situ hybridization (FISH) was performed using a S. mutans
      specific probe. Extracellular cell-bound polysaccharides (EPS) were determined by
      spectrofluorometry from single-species S. mutans biofilms. In the presence of 5 %
      xylitol, the counts of the Xs S. mutans decreased tenfold in the young (8 h)
      biofilm (p < 0.05) but no effect was seen in the mature (24 h) biofilm. No
      decrease was observed for the Xr strains, and FISH confirmed these results. No
      differences were detected in the EPS production of the Xs S. mutans grown with or
      without xylitol, nor between Xr and Xs S. mutans strains. Thus, it seems that
      xylitol did not affect the EPS synthesis of the S. mutans strains. Since the Xr
      S. mutans strains, not inhibited by xylitol, showed no xylitol-induced decrease
      in the biofilms, we conclude that growth inhibition could be responsible for the
      decrease of the counts of the Xs S. mutans strains in the clinically relevant
      young biofilms.

PMID- 22645017
TI  - One-pot controlled synthesis of hexagonal-prismatic Cu1.94S-ZnS, Cu1.94S-ZnS
      Cu1.94S, and Cu1.94S-ZnS-Cu1.94S-ZnS-Cu1.94S heteronanostructures.
AB  - Playing six-a-side: Complex hexagonal prism Cu(1.94)S-ZnS heteronanostructures
      were synthesized by a colloidal route. Cu(1.94)S-ZnS, Cu(1.94)S-ZnS-Cu(1.94)S,
      and Cu(1.94)S-ZnS-Cu(1.94)S-ZnS-Cu(1.94)S structures are formed with screw-,
      dumbbell-, and sandwich-like shapes by using CuI and [Zn(S(2)CNEt(2))(2)] as
      precursors in oleylamine.

PMID- 22645016
TI  - Real-time PCR detection of enteric viruses in source water and treated drinking
      water in Wuhan, China.
AB  - A total of 48 water samples were collected from six water treatment plants in
      Wuhan and analyzed by real-time PCR assay for viral identification of enterovirus
      (EV), rotavirus group A (RVA), human adenovirus (HAdV) as well as human
      adenovirus subgroup F (HAdVF) during the period from December 2010 to October
      2011. HAdV, HAdVF, and RVA were all positively detected in the samples of source
      water and treated drinking water. EV could be found in 46 % (11/24) of all the
      source water samples, but only 21 % (5/24) positive in treated drinking water.
      The concentrations of these three kinds of enteric viruses detected were as
      follows: HAdV > RVA > EV. The highest removal rate was EV (97 %), followed by RVA
      (82 %), HAdV (73 %), and HAdVF (72 %). HAdV and RVA have been abundant in
      untreated river water and finished water after conventional processes of water
      treatment plants, while bacterial indicators could not be detected in tap water,
      which met the standard of China for drinking water bacterial quality. Some
      factors that could affect the accuracy of qPCR detection are also discussed in
      this study.

PMID- 22645018
TI  - Curious encounters during cytopathological evaluation.

PMID- 22645019
TI  - An alfalfa (Medicago sativa L.) ethylene response factor gene, MsERF11, enhances
      salt tolerance in transgenic Arabidopsis.
AB  - A novel orthologue of ethylene response factor gene, MsERF11, was isolated from
      alfalfa in this study. It has an open reading frame of 807 bp, encoding a
      predicted polypeptide of 268 amino acids. Sequence similarity analysis clearly
      suggested that MsERF11 encoded an ethylene response factor protein. The results
      of transient expression of MsERF11 in onion epidermal cells indicated that
      MsERF11 is a nuclear protein. The expression pattern of MsERF11 gene was analyzed
      by real-time quantitative PCR and a higher level of expression was observed in
      leaves than was observed in roots, stems, flower buds and flowers. Furthermore,
      the expression was induced by PEG6000, NaCl, Al2(SO4)3 and six different
      hormones. Over-expressing MsERF11 resulted in enhanced tolerances to salt stress
      in transgenic Arabidopsis plants. This research indicates that MsERF11 has the
      potential to be used for improving crop's salt tolerance in areas where salinity
      is a limiting factor for agricultural productivity. KEY MESSAGE: MsERF11 was
      isolated from alfalfa. Its expression was induced by different abiotic stresses
      and hormones. Over-expressing MsERF11 resulted in enhanced salt tolerance in
      transgenic Arabidopsis plants.

PMID- 22645021
TI  - A tetrathiafulvalene-functionalized radiaannulene with multiple redox states.

PMID- 22645020
TI  - The constitutive expression of Chrysanthemum dichrum ICE1 in Chrysanthemum
      grandiflorum improves the level of low temperature, salinity and drought
      tolerance.
AB  - The quality and productivity of chrysanthemum are severely compromised by various
      abiotic stresses. Here, we describe the isolation of CdICE1 from Chrysanthemum
      dichrum using RACE PCR, which shared identical nucleotide of ICE1 ORF from
      Chrysanthemum grandiflorum variety 'Jinba'. CdICE1 contains a conserved bHLH
      domain, a nuclear localization domain, a S-rich motif and a ACT domain. The
      constitutive expression of CdICE1 in C. grandiflorum improved the tolerance of C.
      grandiflorum to low temperature/freezing, drought and salinity. When the
      transgene was inserted in the antisense direction, the expression of the
      endogenous ICE1 gene was down-regulated, and the level of the plant's sensitivity
      to abiotic stress increased. The level of expression of CgDREBa and CgDREBb,
      activities of superoxide dismutase and peroxidase and the proline content were
      enhanced in the sense transgenic lines, and lowered in the antisense ones under
      stresses. In conclusion, CdICE1 represents a promising candidate for a
      biotechnological approach to improve the level of crop abiotic stress tolerance.
      KEY MESSAGE: Overexpression of CdICE1 in C. grandiflorum confers the stress
      tolerance via its regulation of CgDREB involved in the oxidative and osmotic
      homeostasis pathways.

PMID- 22645022
TI  - Decreased oxidant profile and increased antioxidant capacity in naturally
      postmenopausal women.
AB  - Recent works have shown a dual side of estrogens, and research on the
      relationship between oxidative stress and menopausal status remains unclear and
      has produced controversial results. In this work, we aimed to evaluate by
      sensitive methods the oxidant and antioxidant changes that develop after natural
      menopause. Thirty premenopausal and 28 naturally postmenopausal women volunteered
      for this study. Blood was collected and plasma used. 17-OH estradiol levels in
      plasma were estimated. Plasma levels of advanced oxidation protein products
      (AOPP), lipid peroxidation products (such as hydroperoxides and malondialdehyde
      (MDA)), and nitrites were measured, and total radical antioxidant parameter
      testing was performed to determine the oxidant and antioxidant profiles,
      respectively. Estrogen levels were significantly increased (p < 0.02) in
      premenopausal women (54.28 +/- 9.34 pg/mL) as compared with postmenopausal women
      (18.10 +/- 1.49 pg/mL). Postmenopausal women had lower levels of lipid
      hydroperoxide oxidation (p < 0.0001), lipid hydroperoxide levels evaluated by the
      area under the curve (AUC; 1,366,000 +/- 179,400 AUC; p < 0.01), and
      hydroperoxides as measured by the ferrous oxidation-xylenol orange method (31.48
      +/- 2.7 MUM; p < 0.0001). The MDA levels did not differ between pre- and
      postmenopausal women whether measured by thiobarbituric acid-reactive substances
      or high-performance liquid chromatography assays. No differences in AOPP and
      nitrite levels were observed between pre- and postmenopausal women.
      Postmenopausal women also exhibited a higher total radical antioxidant level
      (0.89 +/- 0.08 MUM Trolox; p < 0.0001). Postmenopausal women demonstrated lower
      levels of oxidative damage and a higher antioxidant capacity than premenopausal
      women.

PMID- 22645023
TI  - Oral supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481
      enhances systemic immunity in elderly subjects.
AB  - Throughout life, there is an aging of the immune system that causes impairment of
      its defense capability. Prevention or delay of this deterioration is considered
      crucial to maintain general health and increase longevity. We evaluated whether
      dietary supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481
      could enhance the immune response in the elderly. This multi-center, double
      blind, and placebo controlled study enrolled 61 elderly volunteers who were
      randomly assigned to receive either placebo or probiotics. Each capsule of
      probiotics contained at least 3 * 10(7)  L. delbrueckii subsp. bulgaricus 8481.
      Individuals in the study were administered three capsules per day for 6 months.
      Blood samples were obtained at baseline (time 0), end of month 3, and month 6. We
      characterized cell subpopulations, measured cytokines by flow cytometry,
      quantified T cell receptor excision circle (TREC) by real-time PCR (RT-PCR), and
      determined human beta-defensin-2 (hBD-2) concentrations and human cytomegalovirus
      (CMV) titers by enzyme-linked immunosorbent assay (ELISA). Elderly responded to
      the intake of probiotic with an increase in the percentage of NK cells, an
      improvement in the parameters defining the immune risk profile (IRP), and an
      increase in the T cell subsets that are less differentiated. The probiotic group
      also showed decreased concentrations of the pro-inflammatory cytokine IL-8 but
      increased antimicrobial peptide hBD-2. These effects disappeared within 6 months
      of stopping the probiotic intake. Immunomodulation induced by L. delbrueckii
      subsp. bulgaricus 8481 could favor the maintenance of an adequate immune
      response, mainly by slowing the aging of the T cell subpopulations and increasing
      the number of immature T cells which are potential responders to new antigens.

PMID- 22645025
TI  - The regents versus the professors: Edward Tolman's role in the California loyalty
      oath controversy.
AB  - In 1950, the University of California Board of Regents approved a policy that all
      faculty members, as a condition for continued employment, were required to either
      sign an oath indicating that they were not members of the Communist Party or
      explain why they would not sign. A group of faculty members, led by psychologist
      Edward Tolman, refused to sign the oath and were fired. This article discusses
      how Tolman emerged as the leader of the faculty nonsigners and how his stature
      within psychology enabled him to recruit assistance from the American
      Psychological Association and the Society for the Psychological Study of Social
      Issues. 

PMID- 22645024
TI  - Caloric restriction-associated remodeling of rat white adipose tissue: effects on
      the growth hormone/insulin-like growth factor-1 axis, sterol regulatory element
      binding protein-1, and macrophage infiltration.
AB  - The role of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis in
      the lifelong caloric restriction (CR)-associated remodeling of white adipose
      tissue (WAT), adipocyte size, and gene expression profiles was explored in this
      study. We analyzed the WAT morphology of 6-7-month-old wild-type Wistar rats fed
      ad libitum (WdAL) or subjected to CR (WdCR), and of heterozygous transgenic dwarf
      rats bearing an anti-sense GH transgene fed ad libitum (TgAL) or subjected to CR
      (TgCR). Although less effective in TgAL, the adipocyte size was significantly
      reduced in WdCR compared with WdAL. This CR effect was blunted in Tg rats. We
      also used high-density oligonucleotide microarrays to examine the gene expression
      profile of WAT of WdAL, WdCR, and TgAL rats. The gene expression profile of WdCR,
      but not TgAL, differed greatly from that of WdAL. The gene clusters with the
      largest changes induced by CR but not by Tg were genes involved in lipid
      biosynthesis and inflammation, particularly sterol regulatory element binding
      proteins (SREBPs)-regulated and macrophage-related genes, respectively. Real-time
      reverse-transcription polymerase chain reaction analysis confirmed that the
      expression of SREBP-1 and its downstream targets was upregulated, whereas the
      macrophage-related genes were downregulated in WdCR, but not in TgAL. In
      addition, CR affected the gene expression profile of Tg rats similarly to wild
      type rats. Our findings suggest that CR-associated remodeling of WAT, which
      involves SREBP-1-mediated transcriptional activation and suppression of
      macrophage infiltration, is regulated in a GH-IGF-1-independent manner. 

PMID- 22645026
TI  - Contextualizing restorative justice for hate crime.
AB  - The application of restorative justice (RJ) with hate crime remains an
      underdeveloped field of research, policy, and practice. This article aims to
      advance the understanding of these two areas of inquiry: RJ and hate crime. It is
      known that while most hate incidents involve minor, punishable offenses, their
      impact can be long lasting and detrimental to victims and affected communities.
      The article investigates how RJ is conceptualized within the hate crime context.
      The findings are based on a 3-year research program, which combined theoretical
      analysis, literature review, and U.K.-focused field research that was carried out
      through a combination of qualitative methods. These included semistructured
      interviews with an expert sample of practitioners and policy makers as well as
      focus groups with young victims and offenders of hate incidents. Direct
      observation was also carried out with two RJ practices.

PMID- 22645027
TI  - The effects of age, authority, and gender on perceptions of statutory rape
      offenders.
AB  - Using a sample of 2,838 students from a Southwestern university in the United
      States, the authors examine the effect of respondent's gender, the adult's
      gender, the age gap between the adult and teen, and the adult's authority, on
      students' perceptions of vignettes describing adult-teen sexual relationships.
      Specifically, the authors investigate four dependent variables related to
      perceptions of the crime: the adult offender's emotional motivation, whether the
      adult is a sexual predator, whether the adult should have limited interactions
      with children, and whether the adult should be included on a sex offender
      registry. ANOVA analysis revealed that a large age gap between the adult and
      teen, the presence of authority in the relationship, and respondent's gender were
      significant predictors of perceptions of the offender as a predator and sex
      offender. The offender's gender significantly predicted respondents' perceived
      motivations but had no effect on opinions regarding sex offender registration.
      The authors discuss the implications of these findings for perceptions of
      statutory rape.

PMID- 22645028
TI  - The relevance of relationship satisfaction and continuation to the gender
      symmetry debate.
AB  - In prior research, Ackerman and Field (2011) found that intimate partner violence
      (IPV) affects the relationship satisfaction of females more than the relationship
      satisfaction of males. The current research replicated those findings on a
      different sample of men and women. In addition to confirming past findings, it
      also found that gendered patterns in IPV differed substantially for current
      versus former relationships. Subsequent analyses indicated that gendered
      differences in whether relationships are continued or terminated after IPV
      apparently explained these patterns. The current analyses illustrate how
      relationship continuation differences across gender can produce sample selection
      biases that substantially affect conclusions about whether partner violence is
      perpetrated equally by men and women. More specifically, the results of this
      research are consistent with the conclusion that female IPV victims are more
      likely than are male victims to become dissatisfied with aggressive opposite-sex
      partnerships and subsequently terminate their aggressive relationships. For this
      reason, research that relies only upon the analysis of current relationships will
      underestimate the amount of partner violence committed by men.

PMID- 22645029
TI  - The utility of risk assessment instruments for the prediction of recidivism in
      sexual homicide perpetrators.
AB  - To examine the predictive accuracy of four well established risk assessment
      instruments (PCL-R, HCR-20, SVR-20, and Static-99) in an important subgroup of
      sexual offenders, these instruments were assessed retrospectively based on
      information from forensic psychiatric court reports in a sample of 90 released
      male sexual homicide offenders (out of an original sample of 166) in Germany.
      Follow-up information about criminal reconvictions after release were obtained
      from the federal criminal records. Total scores as well as subscales and single
      items of these risk assessment instruments did not predict sexual recidivism, and
      only some of them had moderate predictive power regarding nonsexual violent
      recidivism. Possible explanations for these unexpected results are the
      retrospective study design with missing information about influences during the
      long duration of detention and time after release, the small sample size as well
      as the possibility that the risk assessment instruments investigated were valid
      for general sex offender samples, but not for the particular subgroup of
      offenders with sexually motivated homicides.

PMID- 22645030
TI  - Antigenotoxic properties of two newly synthesized beta-aminoketones against N
      methyl-N'-nitro-N-nitrosoguanidine and 9-aminoacridine-induced mutagenesis.
AB  - The aim of this study was to determine the antigenotoxic potential of two newly
      synthesized beta-aminoketones against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
      and 9-aminoacridine (9-AA)-induced mutagenesis. The mutant bacterial tester
      strains were MNNG-sensitive Escherichia coli WP2 uvrA and 9-AA-sensitive
      Salmonella typhimurium TA1537. Both test compounds showed significant
      antimutagenic activity at various tested concentrations. The inhibition rates
      ranged from 29.5% (compound 1: 2 mM/plate) to 47.5% (compound 2: 1.5 mM/plate)
      for MNNG and from 25.0% (compound 2: 1 mM/plate) to 52.1% (compound 2: 2.5
      mM/plate) for 9-AA genotoxicity. Moreover, the mutagenicity of the test compounds
      was investigated by using the same strains. Neither test compound has mutagenic
      properties on the bacterial strains at the tested concentrations. Thus, the
      findings of the present study give valuable information about chemical prevention
      from MNNG and 9-AA genotoxicity by using synthetic beta-aminoketones.

PMID- 22645031
TI  - Image registration for targeted MRI-guided transperineal prostate biopsy.
AB  - PURPOSE: To develop and evaluate image registration methodology for automated re
      identification of tumor-suspicious foci from preprocedural MR exams during MR
      guided transperineal prostate core biopsy. MATERIALS AND METHODS: A hierarchical
      approach for automated registration between planning and intra-procedural T2
      weighted prostate MRI was developed and evaluated on the images acquired during
      10 consecutive MR-guided biopsies. Registration accuracy was quantified at image
      based landmarks and by evaluating spatial overlap for the manually segmented
      prostate and sub-structures. Registration reliability was evaluated by simulating
      initial mis-registration and analyzing the convergence behavior. Registration
      precision was characterized at the planned biopsy targets. RESULTS: The total
      computation time was compatible with a clinical setting, being at most 2 min.
      Deformable registration led to a significant improvement in spatial overlap of
      the prostate and peripheral zone contours compared with both rigid and affine
      registration. Average in-slice landmark registration error was 1.3 +/- 0.5 mm.
      Experiments simulating initial mis-registration resulted in an estimated average
      capture range of 6 mm and an average in-slice registration precision of +/-0.3
      mm. CONCLUSION: Our registration approach requires minimum user interaction and
      is compatible with the time constraints of our interventional clinical workflow.
      The initial evaluation shows acceptable accuracy, reliability and consistency of
      the method.

PMID- 22645032
TI  - The effects of an abundant ectoparasite, the deer ked (Lipoptena cervi), on the
      health of moose (Alces alces) in Finland.
AB  - The deer ked (Lipoptena cervi, Diptera, Hippoboscidae) is a haematophagous
      parasitic fly of the moose (Alces alces) and other cervids, and it is very common
      in southern and central parts of Finland. The aim of this study was to determine
      how the intensive parasitism caused by the deer ked affects the health and
      welfare of the moose. Moose blood samples (n = 78) were collected from deer ked
      infested and ked-free regions at 62-68 degrees  N and analysed for haematology
      and clinical chemistry. In addition, tissue samples of moose (n = 23) were
      collected from a deer ked-infested region at 62 degrees  N to determine how the
      parasite load correlates to several physiological variables of the host. The
      differences in the blood and plasma values between the deer ked-free and ked
      infested animals were minor. In the infested regions, the moose had higher mean
      corpuscular haemoglobin concentrations unlikely to have been caused by the
      parasitism. The intensities of deer keds had no consistent correlations with the
      values of plasma clinical chemistry, endocrinology, amino acids, tissue enzyme
      activities or body energy stores. However, the hepatic percentages of several
      individual n-3 polyunsaturated fatty acids (PUFA) and the n-3 PUFA sum correlated
      inversely with the intensity and density of deer keds. Although a wide array of
      physiological variables was determined, only minor effects caused by the heavy
      deer ked parasitism could be detected, suggesting that the moose might tolerate
      this parasite relatively well.

PMID- 22645033
TI  - Molecular detection and identification of Babesia bovis and Babesia bigemina in
      cattle in northern Thailand.
AB  - Although Babesia bovis and Babesia bigemina infections cause economic losses in
      the cattle industry in northern Thailand, there is inadequate information on
      Babesia isolates present in the area. Therefore, to determine the prevalence and
      genetic relationship between Babesia isolates, we screened 200 blood samples of
      cattle from Chiang Rai, Chiang Mai, and Lumpang provinces of northern Thailand. A
      nested polymerase chain reaction using primers targeting B. bovis spherical body
      protein 2 (BboSBP2) and B. bigemina rhoptry-associated protein 1a (BbiRAP-1a)
      genes revealed a prevalence of 12 and 21 % for B. bovis and B. bigemina,
      respectively, while that of mixed infections was 6.5 % samples. The prevalences
      of B. bovis in Chiang Rai, Chiang Mai, and Lumpang were 9.5, 3.7, and 25.5 %,
      respectively. For B. bigemina, the prevalences were 15.8, 12.9, and 39.2 % in
      Chiang Rai, Chiang Mai, and Lumpang, respectively. Mixed infections with B. bovis
      and B. bigemina were 6.3 % in Chiang Rai, 1.9 % in Chiang Mai, and 13.7 % in
      Lumpang. The identical sequences of either BboSBP2 gene or BbiRAP-1a gene were
      shared among the Babesia isolates in the three provinces of northern Thailand.
      Further analysis using the internal transcribed spacer gene revealed at least
      four genotypes for B. bovis and five genotypes for B. bigemina in northern
      Thailand, while the sequences present great genetic diversities in the different
      isolates. Overall, we have demonstrated a high prevalence and polymorphism of
      Babesia parasites in northern Thailand calling for the need to design effective
      control programs for bovine babesiosis.

PMID- 22645035
TI  - Pulmonary adenofibroma: cytologic and clinicopathologic features of a rare benign
      primary lung lesion.
AB  - We report a case of pulmonary adenofibroma in a 29-year-old female found by CT
      scan during work-up for midline chest pain. To our knowledge, the cytological
      features of this entity have not been previously reported. Cytology demonstrated
      bland epithelial and stromal cells of varying size without karyorrhexis,
      pyknosis, or necrosis and with very rare mitoses. Stromal cells were present as
      either naked bipolar nuclei, as spindle cells with fragile eosinophilic
      cytoplasm, or as rare larger carrot shaped nuclei. Epithelial cells were present
      as small loosely cohesive groups with smooth round nuclei and moderate amounts of
      cytoplasm. Histologically, this lesion consisted of a leaf-like fibroepithelial
      pattern in which the clefts were lined by a single layer of cuboidal epithelium
      reminiscent of adenofibroma occurring in the female genital tract.
      Immunohistochemical analysis demonstrated epithelium that stained positively for
      pan-cytokeratin and TTF-1. The stroma stained positively for vimentin and desmin,
      and was weakly positive for SMA-1. The lesion was confirmed to be pulmonary
      adenofibroma with a smooth muscle component. The differential diagnosis for this
      lesion includes, but is not limited to, pulmonary hamartoma, pulmonary blastoma,
      adenomyofibroma, synovial sarcoma, and visceral metastases. It is important for
      cytopathologists to be aware of this benign entity because it can be encountered
      on lung FNA specimens. Considering this benign lesion in the differential
      diagnosis may help plan for minimal lung resection. Confirmatory intraoperative
      frozen section is a reasonable option.

PMID- 22645034
TI  - Phylogeny of fish-infecting Calyptospora species (Apicomplexa: Eimeriorina).
AB  - There are numerous species of apicomplexans that infect poikilothermic
      vertebrates, such as fishes, and possess unique morphological features that
      provide insight into the evolution of this important phylum of parasites. Here,
      the relationship of the fish-infecting Calyptospora species to other coccidians
      was investigated based on DNA sequence analysis. Genetic data from the small
      subunit ribosomal DNA region of the genome were obtained for three of the five
      nominal species in the genus Calyptospora. Phylogenetic analyses supported a
      monophyletic lineage sister to a group composed of mostly Eimeria species. The
      monophyly of Calyptospora species supports the validity of the family
      Calyptosporidae, but the sister relationship to Eimeria species might also
      suggest the Eimeriidae be expanded to encompass Calyptospora. The validity of the
      family Calyptosporidae has been questioned because it is delineated from the
      Eimeriidae largely based on life cycle characteristics and sporocyst morphology.
      In general, Eimeria species have a homoxenous life cycle, whereas the type
      species of Calyptospora is heteroxenous. In the absence of experimental
      transmission studies, it may be difficult to demonstrate whether all Calyptospora
      species are heteroxenous. Other distinct morphological characteristics of
      Calyptospora such as an incomplete sporocyst suture, an apical opening for
      sporozoite release, a thin veil surrounding sporocysts supported by sporopodia,
      and a lack of Stieda and sub-Stieda bodies suggest there may be adequate features
      to delineate these taxa. Even without life cycle data for all species, the
      morphology and genetic data provide a means to reliably classify Calyptospora
      species. Placement in either the Calyptosporidae or Eimeriidae is discussed,
      along with issues relating to the phylogeny of the genus Goussia.

PMID- 22645036
TI  - Caffeinated alcohol beverages: a public health concern.
AB  - Consumption of alcohol mixed with caffeinated energy drinks is becoming popular,
      and the number of pre-mixed caffeinated alcohol products on the worldwide market
      is increasing. There is public health concern and even occasional legal
      restriction relating to these drinks, due to associations with increased
      intoxication and harms. The precise nature and degree of the pharmacological
      relationship between caffeine and alcohol is not yet elucidated, but it is
      proposed that caffeine attenuates the sedative effects of alcohol intoxication
      while leaving motor and cognitive impairment unaffected. This creates a
      potentially precarious scenario for users who may underestimate their level of
      intoxication and impairment. While legislation in some countries has restricted
      production or marketing of pre-mixed products, many individuals mix their own
      energy drink-alcohol 'cocktails'. Wider dissemination of the risks might help
      balance marketing strategies that over-emphasize putative positive effects.

PMID- 22645037
TI  - Alterations of homocysteine serum levels during alcohol withdrawal are influenced
      by folate and riboflavin: results from the German Investigation on Neurobiology
      in Alcoholism (GINA).
AB  - AIMS: Various studies have shown that plasma homocysteine (HCY) serum levels are
      elevated in actively drinking alcohol-dependent patients a during alcohol
      withdrawal, while rapidly declining during abstinence. Hyperhomocysteinemia has
      been associated not only with blood alcohol concentration (BAC), but also with
      deficiency of different B-vitamins, particularly folate, pyridoxine and
      cobalamin. METHODS: Our study included 168 inpatients (110 men, 58 women) after
      admission for detoxification treatment. BAC, folate, cobalamin, pyridoxine,
      thiamine and riboflavin were obtained on admission (Day 1). HCY was assessed on
      Days 1, 7 and 11. RESULTS: HCY levels significantly declined during withdrawal.
      General linear models and linear regression analysis showed an influence of BAC,
      folate and riboflavin on the HCY levels on admission as well as on HCY changes
      occurring during alcohol withdrawal. No significant influence was found for
      thiamine, cobalamin and pyridoxine. CONCLUSIONS: These findings show that not
      only BAC and plasma folate levels, but also plasma levels of riboflavin influence
      HCY plasma levels in alcohol-dependent patients.

PMID- 22645038
TI  - Acute ethanol does not always affect delay discounting in rats selected to prefer
      or avoid ethanol.
AB  - AIMS: The purpose of this study was to determine whether animals predisposed to
      prefer alcohol possess an altered acute response to alcohol on a delay
      discounting task relative to animals predisposed to avoid alcohol. METHODS: We
      used rats selected to prefer or avoid alcohol to assess whether genotype
      moderates changes in delay discounting induced by acute ethanol exposure.
      Selectively bred rat lines of Sardinian alcohol-preferring (sP; n = 8) and non
      preferring (sNP; n = 8) rats, and alko alcohol (AA, n = 8) and alko non-alcohol
      (ANA, n = 8) rats were trained in an adjusting amount task to assess delay
      discounting. RESULTS: There were no significant effects of line on baseline
      discounting; however, both lines of alcohol-preferring rats exhibit slowed
      reaction times. Acute ethanol (0, 0.25, 0.5 g/kg) treatment also had no effect on
      delay discounting in any of the selectively bred rat lines. CONCLUSION: Our data
      indicate that in these lines of animals, alcohol preference or avoidance has no
      impact on delay discounting following acute ethanol exposure. It is possible that
      other genetic models or lines may be differentially affected by alcohol and
      exhibit qualitatively and quantitatively different responses in delay discounting
      tasks.

PMID- 22645039
TI  - Haemodynamic imaging of thoracic stent-grafts by computational fluid dynamics
      (CFD): presentation of a patient-specific method combining magnetic resonance
      imaging and numerical simulations.
AB  - OBJECTIVES: In the last decade, there was been increasing interest in finding
      imaging techniques able to provide a functional vascular imaging of the thoracic
      aorta. The purpose of this paper is to present an imaging method combining
      magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to obtain
      a patient-specific haemodynamic analysis of patients treated by thoracic
      endovascular aortic repair (TEVAR). METHODS: MRI was used to obtain boundary
      conditions. MR angiography (MRA) was followed by cardiac-gated cine sequences
      which covered the whole thoracic aorta. Phase contrast imaging provided the inlet
      and outlet profiles. A CFD mesh generator was used to model the arterial
      morphology, and wall movements were imposed according to the cine imaging. CFD
      runs were processed using the finite volume (FV) method assuming blood as a
      homogeneous Newtonian fluid. RESULTS: Twenty patients (14 men; mean age 62.2
      years) with different aortic lesions were evaluated. Four-dimensional mapping of
      velocity and wall shear stress were obtained, depicting different patterns of
      flow (laminar, turbulent, stenosis-like) and local alterations of parietal stress
      in-stent and along the native aorta. CONCLUSIONS: A computational method using a
      combined approach with MRI appears feasible and seems promising to provide
      detailed functional analysis of thoracic aorta after stent-graft implantation.
      KEY POINTS : * Functional vascular imaging of the thoracic aorta offers new
      diagnostic opportunities * CFD can model vascular haemodynamics for clinical
      aortic problems * Combining CFD with MRI offers patient specific method of aortic
      analysis * Haemodynamic analysis of stent-grafts could improve clinical
      management and follow-up.

PMID- 22645040
TI  - MR liver imaging with Gd-EOB-DTPA: a delay time of 10 minutes is sufficient for
      lesion characterisation.
AB  - OBJECTIVES: To assess whether, in patients with normal liver function, a
      hepatobiliary delay time of 10 min after Gd-EOB-DTPA injection is sufficient for
      lesion characterisation. METHODS: In 42 consecutive patients with suspected focal
      liver lesions, dynamic MRI was performed after intravenous Gd-EOB-DTPA, followed
      by hepatobiliary phases at 5, 10 and 20 min. The following items were assessed at
      each hepatobiliary phase: parenchymal enhancement, contrast agent excretion in
      bile ducts, lesion enhancement characteristics (hypo-, iso-, or hyperintensity,
      rim enhancement, central non-enhancement), and contrast- and signal-to-noise
      ratios, separately for hypo- and hyperintense lesions. RESULTS: Following
      enhancement, parenchymal signal intensity increased significantly up to 10 min
      (86.3%, P < 0.001), and subsequently stabilised (86.5% after 20 min, P = 0.223).
      Biliary contrast agent excretion was first observed in 2, 32 and 5 patients after
      5, 10 and 20 min respectively. Hepatobiliary lesion enhancement characteristics
      observed after 5 min persisted during later hepatobiliary phases. CNR and SNR
      ratios increased significantly (P < 0.05) up to 10 min after enhancement without
      further increase at 20 min, in hypo- and hyperintense lesions. CONCLUSIONS: If
      lesion characterisation is the primary reason for performing MRI, a hepatobiliary
      delay time of 10 min after Gd-EOB-DTPA injection is sufficient in patients with
      normal liver function. KEY POINTS : * Magnetic resonance imaging is now a first
      line of investigation of the liver. * Optimal CNR and SNR are achieved 10 min
      after Gd-EOB-DTPA injection. * Typical enhancement characteristics are observed
      early and do not change. * Ten-minute hepatobiliary delay is sufficient for
      characterisation of focal liver lesions.

PMID- 22645041
TI  - Prevalence of cartilage lesions and early osteoarthritis in patients with
      patellar dislocation.
AB  - OBJECTIVES: Assessment of cartilage lesions and osteoarthritis (OA) of the
      patellofemoral joint in patients following lateral patellar dislocation using
      magnetic resonance imaging (MRI). METHODS: MR images of 129 knees (mean age 26
      years, range 11-56) grouped as acute (A), recurrent (B), and chronic (C)
      dislocators were analysed regarding the prevalence and severity of patellofemoral
      cartilage lesions. Grades of OA were assessed using modified WORMS. RESULTS: In
      groups A, B, and C the prevalence of cartilage lesions was 71%, 82%, and 97%,
      respectively. Most lesions were located on the central patella in groups A and B
      (central 69% and 78%; medial 56% and 47%; lateral 31% and 42%), whereas group C
      revealed all regions affected (73%, 61%, and 67%). Of group A, 14% had mild OA
      and 64% of group B. Group C showed mild OA in 62% and moderate OA in 18%.
      Cartilage defect size and prevalence of OA was correlated with number of
      dislocations (r = 0.41 and r = 0.59; P < 0.001). CONCLUSIONS: Cartilage lesions
      and early OA are common after patellar dislocation and appear to increase with
      the frequency of dislocation. Both conditions should be considered when
      interpreting MRI in such patients, because of implications for treatment. KEY
      POINTS : * Cartilage lesions are very common after patellar dislocation. * The
      severity of cartilage lesions increases with number of dislocations. *
      Osteoarthritis is common after recurrent patellar dislocation, even in young
      patients. * Detecting cartilage lesions is important after patellar dislocation.

PMID- 22645042
TI  - Shear wave elastography of thyroid nodules in routine clinical practice:
      preliminary observations and utility for detecting malignancy.
AB  - OBJECTIVE: To evaluate real-time shear wave ultrasound elastography (SWE) for
      characterizing focal thyroid lesions in routine clinical practice. METHODS:
      Seventy-four patients with 81 focal thyroid lesions undergoing conventional US
      with needle cytology also underwent SWE. Absolute and relative SWE stiffness
      measurements on colour-coded elastograms were correlated with cytology and their
      discriminatory performances assessed. RESULTS: Seventeen nodules were malignant
      (13 papillary, 4 other cancers), 45 benign (43 hyperplastic nodules, 2 focal
      thyroiditis), 5 indeterminate ("follicular lesions"), and 5 had inadequate
      cytology. SWE results were higher in malignant than benign nodules (P values 0.02
      0.05) although their discriminatory performances were mediocre (AUCs 0.58-0.74).
      The most accurate SWE cut-off, 34.5 kPa for a 2-mm region of interest, achieved
      76.9 % sensitivity and 71.1 % specificity for discriminating papillary cancer
      from benign nodules. No thresholds produced high sensitivity without lowering
      specificity appreciably, and vice versa. Nodule size correlated with SWE for
      benign nodules (P < 0.01). Intranodular cystic change or calcification did not
      influence SWE. Qualitatively, elastographic artefacts and foci lacking colour
      elasticity signal occurred in some solid nodules. CONCLUSION: Although malignant
      nodules are generally stiffer than benign nodules, the precision results do not
      suggest a definitive role for SWE, at present, in identifying or excluding
      thyroid malignancy. KEY POINTS : * Shear wave ultrasound elastography (SWE)
      offers new insight into thyroid disease. * Papillary cancers have higher SWE
      indices (equating to higher stiffness) than benign nodules. * SWE appears limited
      in terms of identifying or excluding thyroid malignancy accurately. * Vertically
      aligned elastographic artefacts can occur in thyroid SWE. * Areas lacking SWE
      colour signal can occur in some solid thyroid nodules.

PMID- 22645043
TI  - Metallic artefact reduction with monoenergetic dual-energy CT: systematic ex vivo
      evaluation of posterior spinal fusion implants from various vendors and different
      spine levels.
AB  - OBJECTIVES: To evaluate optimal monoenergetic dual-energy computed tomography
      (DECT) settings for artefact reduction of posterior spinal fusion implants of
      various vendors and spine levels. METHODS: Posterior spinal fusion implants of
      five vendors for cervical, thoracic and lumbar spine were examined ex vivo with
      single-energy (SE) CT (120 kVp) and DECT (140/100 kVp). Extrapolated
      monoenergetic DECT images at 64, 69, 88, 105 keV and individually adjusted
      monoenergy for optimised image quality (OPTkeV) were generated. Two independent
      radiologists assessed quantitative and qualitative image parameters for each
      device and spine level. RESULTS: Inter-reader agreements of quantitative and
      qualitative parameters were high (ICC = 0.81-1.00, kappa = 0.54-0.77). HU values
      of spinal fusion implants were significantly different among vendors (P < 0.001),
      spine levels (P < 0.01) and among SECT, monoenergetic DECT of 64, 69, 88, 105 keV
      and OPTkeV (P < 0.01). Image quality was significantly (P < 0.001) different
      between datasets and improved with higher monoenergies of DECT compared with SECT
      (V = 0.58, P < 0.001). Artefacts decreased significantly (V = 0.51, P < 0.001) at
      higher monoenergies. OPTkeV values ranged from 123-141 keV. OPTkeV according to
      vendor and spine level are presented herein. CONCLUSIONS: Monoenergetic DECT
      provides significantly better image quality and less metallic artefacts from
      implants than SECT. Use of individual keV values for vendor and spine level is
      recommended. KEY POINTS: * Artefacts pose problems for CT following posterior
      spinal fusion implants. * CT images are interpreted better with monoenergetic
      extrapolation using dual-energy (DE) CT. * DECT extrapolation improves image
      quality and reduces metallic artefacts over SECT. * There were considerable
      differences in monoenergy values among vendors and spine levels. * Use of
      individualised monoenergy values is indicated for different metallic hardware
      devices.

PMID- 22645044
TI  - Evaluation of MR imaging with T1 and T2* mapping for the determination of hepatic
      iron overload.
AB  - OBJECTIVES: To evaluate MRI using T1 and T2* mapping sequences in patients with
      suspected hepatic iron overload (HIO). METHODS: Twenty-five consecutive patients
      with clinically suspected HIO were retrospectively studied. All underwent MRI and
      liver biopsy. For the quantification of liver T2* values we used a fat-saturated
      multi-echo gradient echo sequence with 12 echoes (TR = 200 ms, TE = 0.99 ms +  n
      * 1.41 ms, flip angle 20 degrees ). T1 values were obtained using a fast T1
      mapping sequence based on an inversion recovery snapshot FLASH sequence.
      Parameter maps were analysed using regions of interest. RESULTS: ROC analysis
      calculated cut-off points at 10.07 ms and 15.47 ms for T2* in the determination
      of HIO with accuracy 88 %/88 %, sensitivity 84 %/89.5 % and specificity 100 %/83
      %. MRI correctly classified 20 patients (80 %). All patients with HIO only had
      decreased T1 and T2* relaxation times. There was a significant difference in T1
      between patients with HIO only and patients with HIO and steatohepatitis (P =
      0.018). CONCLUSIONS: MRI-based T2* relaxation diagnoses HIO very accurately, even
      at low iron concentrations. Important additional information may be obtained by
      the combination of T1 and T2* mapping. It is a rapid, non-invasive, accurate and
      reproducible technique for validating the evidence of even low hepatic iron
      concentrations. KEY POINTS: * Hepatic iron overload causes fibrosis, cirrhosis
      and increases hepatocellular carcinoma risk. * MRI detects iron because of the
      field heterogeneity generated by haemosiderin. * T2* relaxation is very accurate
      in diagnosing hepatic iron overload. * Additional information may be obtained by
      T1 and T2* mapping.

PMID- 22645045
TI  - fMRI evaluation of cochlear implant candidacy in diffuse cortical cytomegalovirus
      disease.
AB  - Congenital cytomegalovirus infection is the most frequent nongenetic cause of
      pediatric hearing loss in the United States, affecting approximately 8,000
      children each year. Due in part to variable cytomegalic involvement of the
      auditory cortex, cochlear implantation outcomes have varied widely. Functional
      magnetic resonance imaging (fMRI) has the potential to assist in determining
      candidacy for cochlear implantation through the detection of intact auditory
      pathways including the cortex. We report a case of a 21-month-old girl with
      cytomegalovirus-related deafness and diffuse white matter involvement in which
      fMRI was a determining factor for cochlear implantation and side selection.

PMID- 22645046
TI  - Time-resolved MR angiography of renal artery stenosis in a swine model at 3 Tesla
      using gadobutrol with digital subtraction angiography correlation.
AB  - PURPOSE: To establish the minimum dose required for detection of renal artery
      stenosis using high temporal resolution, contrast enhanced MR angiography (MRA)
      in a porcine model. MATERIALS AND METHODS: Surgically created renal artery
      stenoses were imaged with 3 Tesla MR and digital subtraction angiography (DSA) in
      12 swine in this IACUC approved protocol. Gadobutrol was injected intravenously
      at doses of 0.5, 1, 2, and 4 mL for time-resolved MRA (1.5 * 1.5 mm(2) spatial
      resolution). Region of interest analysis was performed together with stenosis
      assessment and qualitative evaluation by two blinded readers. RESULTS: Mean
      signal to noise ratio (SNR) and contrast to noise ratio (CNR) values were
      statistically significantly less with the 0.5-mL protocol (P < 0.001). There were
      no statistically significant differences among the other evaluated doses. Both
      readers found 10/12 cases with the 0.5-mL protocol to be of inadequate diagnostic
      quality (kappa = 1.0). All other scans were found to be adequate for diagnosis.
      Accuracies in distinguishing between mild/insignificant (<50%) and higher grade
      stenoses (>50%) were comparable among the higher-dose protocols (sensitivities 73
      93%, specificities 62-100%). CONCLUSION: Renal artery stenosis can be assessed
      with very low doses (~0.025 mmol/kg bodyweight) of a high concentration, high
      relaxivity gadolinium chelate formulation in a swine model, results which are
      promising with respect to limiting exposure to gadolinium based contrast agents.

PMID- 22645047
TI  - Cytopathology: a useful technique for diagnosing oral lesions?: a systematic
      literature review.
AB  - Oropharyngeal cancer is the 11th most common cancer worldwide. The diagnostic
      method of choice for oral cavity lesions is biopsy and pathological examination.
      Cytopathology is a simple and inexpensive method, but it is not yet widespread
      among dental professionals. The aim of this study was to evaluate the evidence
      for the effectiveness of cytopathology in diagnosing oral lesions. We conducted a
      systematic literature review of randomized clinical trials that compared the
      diagnostic accuracies of oral lesion cytology and histopathology. We used the
      following search terms: cytology, oral lesions, and oral cancer. The meta
      analysis was performed according to Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses guidelines. Between 1967 and 2010, there were 80
      relevant articles in the literature, 14 of which were included in this study. The
      I-square for sensitivity was 80.2%, and the specificity value was 96.7%. The
      pooled sensitivity was 0.942 [95% confidence interval (CI): 0.926-0.955], and the
      pooled specificity was 0.970 (95% CI: 0.963-0.975). The area under the curve was
      0.9901. Our study suggests that cytology has good sensitivity and specificity for
      the diagnosis of oral lesions and allows the use of other associated techniques,
      such as DNA analysis, which may improve the accuracy of cytology.

PMID- 22645048
TI  - Probing cochlear tuning and tonotopy in the tiger using otoacoustic emissions.
AB  - Otoacoustic emissions (sound emitted from the ear) allow cochlear function to be
      probed noninvasively. The emissions evoked by pure tones, known as stimulus
      frequency emissions (SFOAEs), have been shown to provide reliable estimates of
      peripheral frequency tuning in a variety of mammalian and non-mammalian species.
      Here, we apply the same methodology to explore peripheral auditory function in
      the largest member of the cat family, the tiger (Panthera tigris). We measured
      SFOAEs in 9 unique ears of 5 anesthetized tigers. The tigers, housed at the Henry
      Doorly Zoo (Omaha, NE), were of both sexes and ranged in age from 3 to 10 years.
      SFOAE phase-gradient delays are significantly longer in tigers--by approximately
      a factor of two above 2 kHz and even more at lower frequencies--than in domestic
      cats (Felis catus), a species commonly used in auditory studies. Based on
      correlations between tuning and delay established in other species, our results
      imply that cochlear tuning in the tiger is significantly sharper than in domestic
      cat and appears comparable to that of humans. Furthermore, the SFOAE data
      indicate that tigers have a larger tonotopic mapping constant (mm/octave) than
      domestic cats. A larger mapping constant in tiger is consistent both with
      auditory brainstem response thresholds (that suggest a lower upper frequency
      limit of hearing for the tiger than domestic cat) and with measurements of
      basilar-membrane length (about 1.5 times longer in the tiger than domestic cat).

PMID- 22645049
TI  - Influence of smoking on the pharmacokinetics and toxicity profiles of taxane
      therapy.
AB  - PURPOSE: Cigarette smoke is known to interact with the metabolism of several
      anticancer drugs. It may also affect the incidence and severity of adverse events
      and efficacy of chemotherapy. The main objective of this study was to examine the
      effects of smoking on the pharmacokinetics and toxicities of patients treated
      with docetaxel or paclitaxel. EXPERIMENTAL DESIGN: Smoking status, toxicity
      profiles, and pharmacokinetic parameters (calculated by nonlinear mixed-effect
      modeling population analysis) were determined in 566 patients (429 nonsmokers and
      137 smokers) treated with docetaxel or paclitaxel. RESULTS: Smokers treated with
      docetaxel showed less grade IV neutropenia (35% vs. 52%; P = 0.01) than
      nonsmokers. Smokers treated with paclitaxel had less grade III-IV leukopenia than
      nonsmokers (12% vs. 25%; P = 0.03), and the white blood cell (WBC) nadir was
      lower in nonsmokers (median, 2.7 * 10(9)/L; range, 0.05 * 10(9) to 11.6 *
      10(9)/L) than in smokers (median, 3.3 * 10(9)/L; range 0.8 * 10(9) to 10.2 *
      10(9)/L; P = 0.02). Of interest, significantly lower WBC counts and absolute
      neutrophil counts at baseline were seen in nonsmoking patients treated with
      paclitaxel (P = 0.0001). Pharmacokinetic parameters were similar in smokers and
      nonsmokers for both taxanes. CONCLUSION: Cigarette smoking does not alter the
      pharmacokinetic determinants of docetaxel and paclitaxel. Smokers treated with
      docetaxel and paclitaxel have less neutropenia and leukopenia, but further
      research is warranted to elucidate this potential protective effect.

PMID- 22645050
TI  - Tumor-associated macrophages in pediatric classical Hodgkin lymphoma: association
      with Epstein-Barr virus, lymphocyte subsets, and prognostic impact.
AB  - PURPOSE: Tumor-infiltrating macrophages are associated with adverse outcome in
      adult classical Hodgkin lymphoma (cHL). We have previously shown age-related
      changes in the lymphocyte composition of pediatric cHL. We therefore hypothesized
      that the number, function, and prognostic impact of macrophages in pediatric cHL
      would be different from adult cases. EXPERIMENTAL DESIGN: We analyzed the number
      of macrophages and dendritic cells (DC) in the tumor microenvironment of
      pediatric cHL by immunohistochemistry. Results were analyzed in context of age,
      histologic characteristics, Epstein-Barr virus (EBV) status, clinical follow-up,
      and our previous study of T-cell populations in these cases. RESULTS: One hundred
      cHL cases were studied, including 69% nodular sclerosis and 23% mixed cellularity
      cases. A total of 44.8% of cases were EBV-positive. Patients <=10 years displayed
      more CD14(+) cells (P = 0.025). In comparison with nodular sclerosis, mixed
      cellularity was characterized by higher numbers of CD14(+), (P = 0.003) and
      CD163(+) cells (P = 0.027). EBV(+) cases exhibited higher numbers of CD14(+) (P <
      0.0005), CD68(+) (P = 0.005), and CD163(+) cells (P = 0.02). CD68-positive cells
      did not display an effect on outcome. Worse overall survival was observed in
      cases with CD163/CD8 ratio >=2 (P = 0.007). High numbers of CD163(+) cells were
      associated with worse progression-free survival (PFS; P = 0.015). Furthermore,
      high numbers of CD163(+) and granzyme B(+) cells were associated with worse PFS
      in EBV-negative (P = 0.005) but not in EBV-positive cases. CONCLUSION: Our
      results suggest that macrophage composition in pediatric cHL is distinct from
      adults. Functional status of macrophages and their value as prognostic indicators
      in pediatric cHL may depend on EBV status.

PMID- 22645051
TI  - Pyrophosphorolysis-activated polymerization detects circulating tumor DNA in
      metastatic uveal melanoma.
AB  - PURPOSE: To develop a molecular tool to detect circulating tumor-derived DNA
      (ctDNA) in the plasma from patients with uveal melanoma as a marker of tumor
      burden and monitor treatment efficacy. EXPERIMENTAL DESIGN: A real-time PCR was
      developed on the basis of bidirectional pyrophosphorolysis-activated
      polymerization (bi-PAP) for the quantification of ctDNA using 3'blocked primer
      pairs specific for the 3 recurrent mutually exclusive mutations of Galpha
      subunits GNAQ and GNA11. RESULTS: Sensitivity and specificity of bi-PAP were
      assessed on serial dilutions of tumor DNA in normal DNA for the 3 recurrent
      mutations. Each assay could detect a single mutated molecule per reaction,
      whereas 10(4) copies of normal DNA were not detected. The ctDNA was readily
      detected in plasma of mice bearing uveal melanoma xenografts in amounts
      proportional to circulating human DNA. Finally, plasma was almost always found
      positive (20 of 21 tested patients) in a prospective analysis of patients with
      metastatic uveal melanoma. CONCLUSIONS: Bi-PAP assays detect and quantify ctDNA
      in patients with metastatic uveal melanoma. A prospective study is ongoing to
      assess the clinical usefulness of ctDNA level in uveal melanoma.

PMID- 22645052
TI  - Phase I trial of combretastatin A4 phosphate (CA4P) in combination with
      bevacizumab in patients with advanced cancer.
AB  - PURPOSE: The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P)
      induces significant tumor necrosis as a single agent. Preclinical models have
      shown that the addition of an anti-VEGF antibody to a VDA attenuates the
      revascularization of the surviving tumor rim and thus significantly increases
      antitumor activity. EXPERIMENTAL DESIGN: Patients with advanced solid
      malignancies received CA4P at 45, 54, or 63 mg/m(2) on day 1, day 8, and then
      every 14 days. Bevacizumab 10 mg/kg was given on day 8 and at subsequent cycles
      four hours after CA4P. Functional imaging with dynamic contrast enhanced-MRI (DCE
      MRI) was conducted at baseline, after CA4P alone, and after cycle 1 CA4P +
      bevacizumab. RESULTS: A total of 63 mg/m(2) CA4P + 10 mg/kg bevacizumab q14 is
      the recommended phase II dose. A total of 15 patients were enrolled. Dose
      limiting toxicities were grade III asymptomatic atrial fibrillation and grade IV
      liver hemorrhage in a patient with a history of hemorrhage. Most common
      toxicities were hypertension, headache, lymphopenia, pruritus, and pyrexia.
      Asymptomatic electrocardiographic changes were seen in five patients. Nine of 14
      patients experienced disease stabilization. A patient with ovarian cancer had a
      CA125 response lasting for more than a year. DCE-MRI showed statistically
      significant reductions in tumor perfusion/vascular permeability, which reversed
      after CA4P alone but which were sustained following bevacizumab. Circulating
      CD34(+) and CD133(+) bone marrow progenitors increased following CA4P as did VEGF
      and granulocyte colony-stimulating factor levels. CONCLUSIONS: CA4P in
      combination with bevacizumab appears safe and well tolerated in this dosing
      schedule. CA4P induced profound vascular changes, which were maintained by the
      presence of bevacizumab.

PMID- 22645053
TI  - Wound botulism presenting as a deep neck space infection.
AB  - Otolaryngologists commonly evaluate patients with findings suspicious for deep
      space soft tissue infections of the neck. In this case, a woman with a history of
      injection drug use (IDU) presented with dysphagia, odynophagia, and neck pain.
      Multiple neck abscesses, too small to drain, were seen on imaging. Despite broad
      spectrum intravenous antibiotics, she unexpectedly and rapidly developed
      respiratory failure requiring intubation. Further work-up diagnosed wound
      botulism (WB). To our knowledge, this is the first report of WB presenting as a
      deep neck space infection, and illustrates the importance of considering this
      deadly diagnosis in patients with IDU history and bulbar symptoms.

PMID- 22645054
TI  - Aloe-emodin inhibits adipocyte differentiation and maturation during in vitro
      human mesenchymal stem cell adipogenesis.
AB  - In this study, we examined the effects of Aloe-emodin (AE) on the inhibition of
      adipocyte differentiation during 3-isobutyl-1-methylxanthine (IBMX)-induced
      adipocyte differentiation in human mesenchymal stem cells (hMSCs). AE treatment
      (5, 10, and 20 uM) of preadipocyte cells resulted in a significant (p < 0.05)
      decrease in glycerol phosphate dehydrogenase and triglyceride levels as well as
      an increase in lactate dehydrogenase activity and attenuated lipid accumulation
      compared with untreated differentiated adipocytes. Using quantitative reverse
      transcription polymerase chain reaction, we studied the mRNA expression levels of
      resistin, adiponectin, aP(2), lipoprotein lipase, PPARgamma, and tumor necrosis
      factor-alpha in hMSCs undergoing adipocyte differentiation; treatment with AE
      decreased the expression of these adipogenic genes and decreased adipocyte
      differentiation. In addition, AE suppresses the differentiation of hMSCs into
      adipocytes by downregulating PPARgamma and C/EBPalpha expressions. AE
      significantly inhibited hMSCs proliferation and preadipocyte differentiation
      within the first 2 days of treatment, indicating that the antiadipogenic effect.

PMID- 22645055
TI  - Fine-needle aspiration diagnosis of sclerosing hemangioma (pneumocytoma): report
      of a case and review of the literature.
AB  - Sclerosing hemangioma (pneumocytoma) is a rare benign lung tumor with uncertain
      histogenesis but characteristic histology. Reports of the cytopathology of this
      tumor are even rarer with only a handful of cases in the literature--many of
      these incorrectly diagnosed by cytology initially. Herein, we describe a case of
      sclerosing hemangioma diagnosed prima facie by fine-needle aspiration cytology. A
      cell block preparation with accompanying immunohistochemistry was instrumental in
      making the diagnosis. A review of the literature is also presented.

PMID- 22645056
TI  - Should I stay or should I go?: Physiological, metabolic and biochemical
      consequences of voluntary emersion upon aquatic hypoxia in the scaleless fish
      Galaxias maculatus.
AB  - Hypoxia represents a significant challenge to most fish, forcing the development
      of behavioural, physiological and biochemical adaptations to survive. It has been
      previously shown that inanga (Galaxias maculatus) display a complex behavioural
      repertoire to escape aquatic hypoxia, finishing with the fish voluntarily
      emerging from the water and aerially respiring. In the present study we evaluated
      the physiological, metabolic and biochemical consequences of both aquatic hypoxia
      and emersion in inanga. Inanga successfully tolerated up to 6 h of aquatic
      hypoxia or emersion. Initially, this involved enhancing blood oxygen-carrying
      capacity, followed by the induction of anaerobic metabolism. Only minor changes
      were noted between emersed fish and those maintained in aquatic hypoxia, with the
      latter group displaying a higher mean cell haemoglobin content and a reduced
      haematocrit after 6 h. Calculations suggest that inanga exposed to both aquatic
      hypoxia and air reduced oxygen uptake and also increased anaerobic contribution
      to meet energy demands, but the extent of these changes was small compared with
      hypoxia-tolerant fish species. Overall, these findings add to previous studies
      suggesting that inanga are relatively poorly adapted to survive aquatic hypoxia.

PMID- 22645057
TI  - Comparative effectiveness of donation after cardiac death versus donation after
      brain death liver transplantation: Recognizing who can benefit.
AB  - Due to organ scarcity and wait-list mortality, transplantation of donation after
      cardiac death (DCD) livers has increased. However, the group of patients
      benefiting from DCD liver transplantation is unknown. We studied the comparative
      effectiveness of DCD versus donation after brain death (DBD) liver
      transplantation. A Markov model was constructed to compare undergoing DCD
      transplantation with remaining on the wait-list until death or DBD liver
      transplantation. Differences in life years, quality-adjusted life years (QALYs),
      and costs according to candidate Model for End-Stage Liver Disease (MELD) score
      were considered. A separate model for hepatocellular carcinoma (HCC) patients
      with and without MELD exception points was constructed. For patients with a MELD
      score <15, DCD transplantation resulted in greater costs and reduced
      effectiveness. Patients with a MELD score of 15 to 20 experienced an improvement
      in effectiveness (0.07 QALYs) with DCD liver transplantation, but the incremental
      cost-effectiveness ratio (ICER) was >$2,000,000/QALY. Patients with MELD scores
      of 21 to 30 (0.25 QALYs) and >30 (0.83 QALYs) also benefited from DCD
      transplantation with ICERs of $478,222/QALY and $120,144/QALY, respectively.
      Sensitivity analyses demonstrated stable results for MELD scores <15 and >20, but
      the preferred strategy for the MELD 15 to 20 category was uncertain. DCD
      transplantation was associated with increased costs and reduced survival for HCC
      patients with exception points but led to improved survival (0.26 QALYs) at a
      cost of $392,067/QALY for patients without exception points. In conclusion, DCD
      liver transplantation results in inferior survival for patients with a MELD score
      <15 and HCC patients receiving MELD exception points, but provides a survival
      benefit to patients with a MELD score >20 and to HCC patients without MELD
      exception points.

PMID- 22645058
TI  - Magnetic resonance imaging based determination of body compartments with the
      versatile, interactive sparse sampling (VISS) method.
AB  - PURPOSE: To investigate the inhomogeneity of radiofrequency fields at higher
      field strengths that can interfere with established volumetric methods, in
      particular for the determination of visceral (VAT) and subcutaneous adipose
      tissue (SCAT). A versatile, interactive sparse sampling (VISS) method is proposed
      to determine VAT, SCAT, and also total body volume (TBV). MATERIALS AND METHODS:
      VISS is based on a separation of major components by contour lines, followed by a
      sparse sampling algorithm, and eventually a quick manual correction. T1-weighted
      whole body scans of 24 subjects were evaluated (12 at 1.5T, 12 at 3.0T). RESULTS:
      (a) Coefficients of variance (CV) and intra class correlation coefficients (ICC)
      determined within 3 raters (24 subjects) showed high consistency for SCAT (CV
      2.2%, ICC 0.993) and VAT (CV 4.9%, ICC 0.987), (b) comparison with an established
      volumetric method revealed good agreement (Bland-Altman, VAT -0.68L to 1.07L,
      SCAT -2.18L to 8.39L), and (c) comparison of weights calculated from TBV with
      values measured on a scale resulted in an even better accuracy for VISS (Bland
      Altman -1.98 kg to 4.09 kg) than for the reference method (-5.60 kg to 1.60 kg).
      CONCLUSION: VISS is reproducible in particular within the same rater, accurate as
      compared with established methods, and robust against low contrast and
      inhomogeneity artifacts.

PMID- 22645059
TI  - Positive effect of eplerenone treatment on endothelial progenitor cells in
      patients with chronic heart failure.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) are known to play a significant
      role in reendothelialization and vascular repair. Recently, a mineralocorticoid
      receptor was demonstrated to be expressed by EPCs. The study aimed to evaluate a
      potential influence of eplerenone treatment on the total number of EPCs in
      patients with chronic heart failure. METHODS: Eighty-seven male patients with
      chronic heart failure were included (age: 23-83 years; body mass index 29.1 +/-
      5.1 kg/m2; New York Heart failure classification (NYHA) I: 29 patients, NYHA II:
      32 patients, NYHA III: 26 patients). Numbers of circulating EPCs were quantified
      immediately using flow cytometry. Twenty-eight patients received therapy with
      eplerenone. Patients were further characterized by echocardiography, spirometry
      and laboratory markers. RESULTS: Patients with ongoing eplerenone administration
      showed higher levels of circulating cells expressing CD34+ (p<0.05) and CD34+KDR+
      (p<0.05) and CD34+CD133+KDR+ cells (p<0.05). The effects of eplerenone treatment
      could be shown to be independent of NYHA status, genesis of the underlying
      cardiovascular morbidity, left ventricular function and co-medication.
      CONCLUSION: Patients with chronic heart failure treated with eplerenone show
      higher numbers of EPCs. The clinical benefit for treatment with eplerenone has
      been demonstrated even for patients with mild heart failure and might be
      partially mediated by EPCs.

PMID- 22645060
TI  - Association study of angiotensin II type 1 receptor: A1166C (rs5186) polymorphism
      with coronary heart disease using systematic meta-analysis.
AB  - Angiotensin II type 1 receptor (AT1R) mediates the cardiovascular actions of
      angiotensin II. Growing studies have revealed the underlying association between
      AT1R-A1166C (rs5186) polymorphism and coronary heart disease (CHD) among the East
      Asia population. RESULTS: from these studies remain conflicting. We conducted
      this meta-analysis to estimate the overall CHD risk of AT1R-A1166C polymorphism
      regarding the East Asia population. We searched the PubMed, Embase and China
      National Knowledge Infrastructure (CNKI) databases for all articles within a
      range of published years from 1995 to 2011. The odds ratio (OR) corresponding to
      the 95% confidence interval (CI) was used to assess the different associations.
      The statistical heterogeneity among studies was assessed with the Q-test and I
      (2) statistics. Up to December 2011, 17 case-control studies, including 2,366
      cases and 2,414 controls, were available for our study. The C allele and the
      AC/CC genotypes were associated with significantly increased risk of CHD (OR =
      1.59, 95% CI = 1.22-2.06 for C versus A and OR = 1.57, 95% CI = 1.16-2.13 for
      AC/CC versus AA, respectively). Our result suggested that AT1R-A1166C
      polymorphism may be involved in the development of CHD.

PMID- 22645061
TI  - Left ventricle remodeling in men with moderate to severe volume-dependent
      hypertension.
AB  - We evaluated the influence of increased intravascular volume on the heart anatomy
      in salt-sensitive types of hypertension, represented by primary aldosteronism
      (PA) and low-renin essential hypertension (LREH). Echocardiography was performed
      in 128 males with moderate to severe or resistant hypertension: 44 patients had
      PA, 40 patients had LREH and 44 patients had normal-renin essential hypertension
      (NREH). Groups were comparable in demographic characteristics, blood pressure,
      duration of hypertension and previous antihypertensive treatment. Patients with
      PA and LREH, in comparison with NREH patients, showed both greater end-systolic
      (37.6+/-5.4 and 35.6+/-4.5 vs 32.6+/-4.4 mm, p<0.001 and p<0.05) and end
      diastolic (56.1+/-4.5 and 54.0+/-4.8 vs 50.4+/-5.1 mm; p<0.001 and p<0.01) left
      ventricle (LV) diameter. There were no significant differences either in LV wall
      thicknesses or LV mass, although a higher percentage of patients with PA and LREH
      met the criteria of eccentric hypertrophy (p<0.001 and p<0.05 respectively).
      Aldosterone concentration was positively related to LV cavity dimensions, whether
      wall thicknesses were rather associated with blood pressure levels. In
      conclusion, plasma volume overload was identified as an important factor
      influencing LV remodeling in PA and LREH, whether due to excessive aldosterone
      levels in PA or other pathophysiological mechanisms.

PMID- 22645062
TI  - Plasma leptin, neuropeptide Y, ghrelin, and adiponectin levels and carotid artery
      intima media thickness in epileptic children treated with valproate.
AB  - BACKGROUND: Weight gain is a common side effect of valproate (VPA) treatment,
      although the mechanism is not clear. Abnormal weight gain and obesity are
      associated with dyslipidemia, hypertension, and atherosclerosis. Measurement of
      the common carotid artery intima media thickness (CAIMT) gives a picture of early
      arterial wall alterations and, currently, is considered a noninvasive marker of
      premature atherosclerosis. The aim of the present study was to evaluate plasma
      insulin, leptin, neuropeptide Y (NPY), ghrelin, and adiponectin levels in
      children with epilepsy treated with VPA and to evaluate these parameters for
      early atherosclerosis. MATERIAL AND METHODS: Twenty prepubertal children with
      idiopathic epilepsy treated with VPA were enrolled in this study. Body mass index
      (BMI) and fasting insulin glucose ratio (FIGR) were calculated, and the plasma
      insulin, leptin, NPY, ghrelin, and adiponectin levels; the lipid profiles; and
      CAIMT were measured for all subjects before the treatment and after a follow-up
      period of 6 and 12 months. RESULTS: When pretreatment values were compared with
      those at the end of 6 and 12 months, the mean BMI values, plasma insulin, leptin,
      NPY levels, and FIGR were increased, whereas the plasma ghrelin and adiponectin
      levels, lipid profiles, and CAIMT did not change significantly at the end of 6
      and 12 months. CONCLUSION: These results suggest that weight gain during VPA
      treatment may be related to increases in insulin, leptin, and NPY levels.
      Additionally, in this study, no increase in the risk for early atherosclerosis
      was determined by CAIMT in children with epilepsy treated with VPA.

PMID- 22645063
TI  - Congenital paediatric atlantoaxial dislocation: clinico-radiological profile and
      surgical outcome.
AB  - INTRODUCTION: Congenital atlantoaxial dislocation (AAD) is the most common bony
      abnormality affecting the craniovertebral junction. The paediatric population has
      specific problems like preoperative diagnostic difficulties, precise neurological
      examination, radiological diagnosis, surgical problems including physical fitness
      to tolerate surgery (including problems of anaesthesia), technical difficulties
      in surgery and problems related to immobilization. MATERIAL AND METHODS: A total
      of 229 consecutive paediatric (<=18 years) patients of AAD visited our centre
      from the period of January 1997 to August 2011. Twenty-nine cases were excluded
      from the study as these cases were diagnosed as CVJ tuberculosis, 31 cases were
      excluded as they were traumatic and the remaining 169 cases were retrospectively
      analysed. These patients were operated by a single experienced surgeon (the
      senior author) at the Sanjay Gandhi Post Graduate Institute of Medical Sciences,
      Lucknow. The preoperative and the postoperative clinical evaluation of the
      patient was done by the Kumar and Kalra myelopathic scoring system. The score was
      recorded in the preoperative period, at the time of discharge, at 3 months follow
      up and at 6 months follow-up. RESULTS: Ninety-four were males and 75 were
      females. The age range was 4 to 18 years with mean age 9.96+/-3.78 years. The
      follow-up ranged from 3 to 120 months with mean follow-up being 39.03+/-13.38
      months. One hundred five cases were of fixed/irreducible AAD, and 64 were cases
      of mobile/reducible AAD. Majority of these cases presented with features of
      pyramidal tract involvement, and 108 cases had compromised pulmonary function
      test. One hundred thirty-seven cases had improved outcome, and 18 cases were in
      the same grade in the postoperative period with only 14 cases either deteriorated
      or died. CONCLUSIONS: Congenital paediatric AAD are a different subset of
      abnormalities and have a satisfactory outcome. Preoperative evaluation must also
      include identification of various syndromes associated with paediatric AAD and
      respiratory reserve. Cormack-Lehane grade can be helpful in selecting borderline
      cases for postoperative need of tracheostomy. Majority of the cases have a good
      outcome, and therefore, surgery should be offered even in severe grade.

PMID- 22645064
TI  - Chemoprophylaxis with isoniazid in liver transplant recipients.
AB  - A patient receiving a liver graft needs to be treated with immunosuppressive
      drugs to avoid rejection. These kinds of drugs predispose the patient to the
      reactivation of latent infections such as tuberculosis (TB). Therefore, it is
      necessary to establish treatment regimens to prevent this. We retrospectively
      analyzed all consecutive patients undergoing liver transplantation (LT) at our
      center between January 1, 2000 and December 31, 2010. Latent tuberculosis
      infections (LTBIs) were diagnosed with positive tuberculin skin test results.
      After LT, infected patients were treated with isoniazid for 6 months; the
      treatment began soon after transplantation, and the patients were followed until
      the end of the study. During this period, 53 patients had LTBI data. All these
      patients were treated with isoniazid after LT. The median observation period
      after LT was 52 months (range = 12-129 months). No cases of TB reactivation were
      reported during follow-up. Only 4 patients presented alterations in liver enzymes
      related to this treatment, and they showed clear improvement after the treatment
      was stopped. None of these patients showed severe graft dysfunction. In
      conclusion, preventive isoniazid appears to be a safe drug for use in LTBI
      patients after LT. The treatment may be established just after LT without
      important graft dysfunction or severe consequences for the patient.

PMID- 22645065
TI  - Caution should be used in applying propensity scores estimated in a full cohort
      to adjust for confounding in subgroup analyses: commentary on "Applying
      propensity scores estimated in a full cohort to adjust for confounding in
      subgroup analyses": Commentary on "Applying propensity scores estimated in a full
      cohort to adjust for confounding in subgroup analyses"

PMID- 22645066
TI  - Study on organochlorine pesticide levels in chronic kidney disease patients:
      association with estimated glomerular filtration rate and oxidative stress.
AB  - Nephrotoxicity of organochlorine pesticides (OCPs) has been established in
      experimental animal models. This study was designed to evaluate the relationship
      of the blood OCPs level with the estimated glomerular filtration rate (eGFR) and
      oxidative stress (OS) in chronic kidney disease (CKD) patients. Patients in
      different stages of CKD (n = 150) and age, sex matched healthy controls (n = 96)
      were recruited. The blood OCPs level were analyzed by gas chromatography, and
      plasma levels of several OS parameters such as malondialdehyde (MDA), protein
      carbonyl, advanced oxidation protein products (AOPP), and total thiols were
      quantified by standard spectrophotometric methods. We observed significantly
      higher levels of hexachlorocyclohexane (alpha, gamma), endosulfan, aldrin, p,p'
      dichlorodiphenyldichloroethylene (DDE), and total pesticides in CKD patients.
      Negative correlation was also observed for aldrin, p,p'-DDE and total pesticides
      (p < 0.05) with eGFR. Plasma levels of MDA and AOPP showed significant positive
      association with the total pesticides level, indicating augmentation of OS with
      increased accumulation of OCPs in CKD patients.

PMID- 22645067
TI  - Balance disorders in the elderly: epidemiology and functional impact.
AB  - OBJECTIVES/HYPOTHESIS: To quantify the prevalence and determine the impact of
      dizziness and balance disorders in the elderly. STUDY DESIGN: Cross-sectional
      analysis of a national database. METHODS: The balance problems survey module of
      the 2008 National Health Interview Survey was examined, and cases of reported
      dizziness or balance problems in persons >=65 years old were identified. The
      prevalence of balance disorders and associated symptoms and their impacts on self
      reported functional limitations were determined. The related impact on daily
      activities for elderly persons with balance problems was quantified. Sex-based
      differences in balance problems were determined. RESULTS: Among 37.3 +/- 0.9
      million elderly persons (mean age, 74.4 +/- 0.1 years; 56.9% +/- 0.9% female),
      7.0 +/- 0.2 million persons (19.6% +/- 0.7%) reported a problem with dizziness or
      balance in the preceding 12 months. Balance problems included difficulty with
      unsteadiness (68.0%), walking on uneven surfaces (54.8%), vertigo (30.1%), and
      faintness (29.6%). Prescription medication triggered the balance problem in
      18.7%. Among the 50.0% of elderly persons with balance problems who sought care,
      85.6%, 30.3%, 23.9%, and 16.8% saw a general practitioner, internist,
      neurologist, or otolaryngologist, respectively. Of this group, 27.4% reported
      that balance problems specifically prevented them from participating in
      activities including exercise (61.2%), social events (45.8%), and driving
      (47.1%). Females were more likely to experience balance problems than males
      (21.0% vs. 17.7%, P = .025). CONCLUSIONS: Approximately one in five elderly
      persons experiences annual problems with dizziness or balance. Given the
      significant prevalence and negative effect of balance problems on daily
      activities in the elderly, balance disorders merit special attention,
      particularly in the face of an aging population.

PMID- 22645068
TI  - Selenium distribution and speciation in the hyperaccumulator Astragalus
      bisulcatus and associated ecological partners.
AB  - The goal of this study was to investigate how plant selenium (Se)
      hyperaccumulation may affect ecological interactions and whether associated
      partners may affect Se hyperaccumulation. The Se hyperaccumulator Astragalus
      bisulcatus was collected in its natural seleniferous habitat, and x-ray
      fluorescence mapping and x-ray absorption near-edge structure spectroscopy were
      used to characterize Se distribution and speciation in all organs as well as in
      encountered microbial symbionts and herbivores. Se was present at high levels
      (704-4,661 mg kg(-1) dry weight) in all organs, mainly as organic C-Se-C
      compounds (i.e. Se bonded to two carbon atoms, e.g. methylselenocysteine). In
      nodule, root, and stem, up to 34% of Se was found as elemental Se, which was
      potentially due to microbial activity. In addition to a nitrogen-fixing symbiont,
      the plants harbored an endophytic fungus that produced elemental Se. Furthermore,
      two Se-resistant herbivorous moths were discovered on A. bisulcatus, one of which
      was parasitized by a wasp. Adult moths, larvae, and wasps all accumulated
      predominantly C-Se-C compounds. In conclusion, hyperaccumulators live in
      association with a variety of Se-resistant ecological partners. Among these
      partners, microbial endosymbionts may affect Se speciation in hyperaccumulators.
      Hyperaccumulators have been shown earlier to negatively affect Se-sensitive
      ecological partners while apparently offering a niche for Se-resistant partners.
      Through their positive and negative effects on different ecological partners,
      hyperaccumulators may influence species composition and Se cycling in
      seleniferous ecosystems.

PMID- 22645069
TI  - Environmental stresses of field growth allow cinnamyl alcohol dehydrogenase
      deficient Nicotiana attenuata plants to compensate for their structural
      deficiencies.
AB  - The organized lignocellulosic assemblies of cell walls provide the structural
      integrity required for the large statures of terrestrial plants. Silencing two
      CINNAMYL ALCOHOL DEHYDROGENASE (CAD) genes in Nicotiana attenuata produced plants
      (ir-CAD) with thin, red-pigmented stems, low CAD and sinapyl alcohol
      dehydrogenase activity, low lignin contents, and rubbery, structurally unstable
      stems when grown in the glasshouse (GH). However, when planted into their native
      desert habitat, ir-CAD plants produced robust stems that survived wind storms as
      well as the wild-type plants. Despite efficient silencing of NaCAD transcripts
      and enzymatic activity, field-grown ir-CAD plants had delayed and restricted
      spread of red stem pigmentation, a color change reflecting blocked lignification
      by CAD silencing, and attained wild-type-comparable total lignin contents. The
      rubbery GH phenotype was largely restored when field-grown ir-CAD plants were
      protected from wind, herbivore attack, and ultraviolet B exposure and grown in
      restricted rooting volumes; conversely, it was lost when ir-CAD plants were
      experimentally exposed to wind, ultraviolet B, and grown in large pots in growth
      chambers. Transcript and liquid chromatography-electrospray ionization-time-of
      flight analysis revealed that these environmental stresses enhanced the
      accumulation of various phenylpropanoids in stems of field-grown plants; gas
      chromatography-mass spectrometry and nuclear magnetic resonance analysis revealed
      that the lignin of field-grown ir-CAD plants had GH-grown comparable levels of
      sinapaldehyde and syringaldehyde cross-linked into their lignins. Additionally,
      field-grown ir-CAD plants had short, thick stems with normal xylem element
      traits, which collectively enabled field-grown ir-CAD plants to compensate for
      the structural deficiencies associated with CAD silencing. Environmental stresses
      play an essential role in regulating lignin biosynthesis in lignin-deficient
      plants.

PMID- 22645071
TI  - Socioeconomic disparities in the quality of life in children with cancer or brain
      tumors: the mediating role of family factors.
AB  - OBJECTIVE: This study aimed to determine if and to what extent (i) socioeconomic
      disparities exist in the health-related quality of life (QOL) of children with
      cancer or brain tumors and healthy children; and (ii) family functioning and
      burden mediate the relationship between socioeconomic status and children's QOL.
      METHODS: In this cross-sectional study, parents of children ages 2-18 with (n =
      71) and without (n = 135) cancer or brain tumors completed in-person interviewer
      assisted surveys assessing sociodemographics (including income and parental
      education), child QOL (measure: PedsQL), family functioning (measure: Family
      Adaptability and Cohesion Evaluation Scale IV) and burden (measure: Impact on the
      Family Scale). For children with cancer, clinical characteristics were captured
      through medical record abstraction. Multiple linear regression was used to
      determine the relationship between income and child QOL; the interaction between
      group status and income was assessed. Staged multivariate regression models were
      used to assess the role of family factors in this relationship among children
      with cancer. RESULTS: In multivariate analyses, the effect of income differed by
      cancer status; lower income was associated with worse QOL in children with cancer
      but not among healthy children. Among children with cancer, this relationship was
      significantly attenuated by family burden. CONCLUSIONS: Significant socioeconomic
      disparities exist in the QOL of children with cancer. Family factors partially
      explain the relationship between low income and poor QOL outcomes among these
      children. Lower-income families may have fewer resources to cope with their
      child's cancer. Increased support, monitoring, and referrals to reduce burden for
      these families may lead to improved QOL in children with cancer.

PMID- 22645070
TI  - Effect of arabinogalactan proteins from the root caps of pea and Brassica napus
      on Aphanomyces euteiches zoospore chemotaxis and germination.
AB  - Root tips of many plant species release a number of border, or border-like, cells
      that are thought to play a major role in the protection of root meristem.
      However, little is currently known on the structure and function of the cell wall
      components of such root cells. Here, we investigate the sugar composition of the
      cell wall of the root cap in two species: pea (Pisum sativum), which makes border
      cells, and Brassica napus, which makes border-like cells. We find that the cell
      walls are highly enriched in arabinose and galactose, two major residues of
      arabinogalactan proteins. We confirm the presence of arabinogalactan protein
      epitopes on root cap cell walls using immunofluorescence microscopy. We then
      focused on these proteoglycans by analyzing their carbohydrate moieties,
      linkages, and electrophoretic characteristics. The data reveal (1) significant
      structural differences between B. napus and pea root cap arabinogalactan proteins
      and (2) a cross-link between these proteoglycans and pectic polysaccharides.
      Finally, we assessed the impact of root cap arabinogalactan proteins on the
      behavior of zoospores of Aphanomyces euteiches, an oomycetous pathogen of pea
      roots. We find that although the arabinogalactan proteins of both species induce
      encystment and prevent germination, the effects of both species are similar.
      However, the arabinogalactan protein fraction from pea attracts zoospores far
      more effectively than that from B. napus. This suggests that root arabinogalactan
      proteins are involved in the control of early infection of roots and highlights a
      novel role for these proteoglycans in root-microbe interactions.

PMID- 22645072
TI  - Inhibition of vascular smooth muscle cell proliferation and migration in vitro
      and neointimal hyperplasia in vivo by adenoviral-mediated atrial natriuretic
      peptide delivery.
AB  - BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation and migration are
      important components of the remodeling process in atherosclerosis or following
      angioplasty. Atrial natriuretic peptide (ANP) inhibits the growth of VSMCs in
      vitro but this effect has not been proven in vivo. In the present study, we
      examined the effects of local overexpression of ANP following gene transfer on in
      vitro VSMC proliferation and migration and in vivo neointimal formation in a rat
      carotid artery model of vascular injury. METHODS: ANP gene transfer was performed
      using a recombinant adenovirus containing the ANP cDNA controlled by the Rous
      sarcoma virus (RSV) long terminal repeat (Ad-RSV-ANP). A recombinant adenovirus
      expressing the RSV-controlled beta-galactosidase gene (Ad-RSV-beta-gal) was used
      as the control. Rat VSMC culture was used for in vitro studies. In the in vivo
      experiments, carotid arteries were analyzed after balloon injury and local
      infusion of the viral solution. RESULTS: VSMCs transfected by Ad-RSV-ANP produced
      a significant amount of ANP detected by immunoreactive assay and accumulated
      about 6.5 times more cGMP than the viral control. VSMC proliferation stimulated
      with 10% fetal calf serum was reduced by 31% and migration by 25%. Fourteen days
      after injury, neointimal formation and the intima/media ratio were reduced by 25%
      and 28%, respectively, in the Ad-RSV-ANP-treated group compared to the control
      group. CONCLUSIONS: The present study demonstrates the efficacy of recombinant
      adenovirus Ad-RSV-ANP with respect to inhibiting rat VSMC proliferation and
      migration. Our findings also provide evidence that ANP is implicated in the
      modulation of vascular remodeling following endothelial injury.

PMID- 22645073
TI  - Otolaryngologists' perceptions of odontogenic maxillary sinusitis.
AB  - OBJECTIVES/HYPOTHESIS: Odontogenic maxillary sinusitis (OMS) is a common cause of
      chronic rhinosinusitis (CRS); however, the condition is infrequently mentioned in
      recent rhinosinusitis guidelines and often overlooked as a cause of sinusitis by
      otolaryngologists, dentists, and radiologists. The goal of this survey is to
      assess otolaryngologists' perceptions of the incidence, diagnosis, and treatment
      of OMS. STUDY DESIGN: Physician survey. METHODS: Ninety-three board certified
      otolaryngologists in the United States completed a 17-question survey on
      etiologies of CRS, which also included questions on alternative diagnoses and
      radiologic findings to reduce respondent bias toward the survey's focus on
      odontogenic sinusitis. Results were compared between self-reported general
      otolaryngologists and rhinologists. RESULTS: Both groups recognized an
      odontogenic source as a common cause of maxillary sinusitis and reported treating
      an average of 2.9 patients per year with OMS who were initially misdiagnosed.
      Most otolaryngologists surveyed perceived radiologists to never or rarely report
      on dental pathology in their sinus computed tomography (CT) interpretation.
      CONCLUSIONS: Both general otolaryngologists and rhinologists recognize
      odontogenic sinusitis is common, although often initially misdiagnosed. With
      increasing awareness of OMS, we believe that otolaryngologists and radiologists
      will review sinus CT scans for the presence of periapical abscesses and dental
      pathology. The otolaryngologist should suspect an odontogenic etiology of
      purulent maxillary CRS in patients failing to improve with antibiotics,
      regardless of a negative dental workup.

PMID- 22645074
TI  - Expression of vascular endothelial growth factor can predict distant metastasis
      and disease-free survival for clinical stage III rectal cancer following 30-Gy/10
      f preoperative radiotherapy.
AB  - PURPOSE: The purpose of this study was to analyze the prognostic value of
      vascular endothelial growth factor (VEGF) in patients with stage III rectal
      cancer treated with 30-Gy/10-fraction (f) preoperative radiotherapy and radical
      surgery. METHODS: One hundred and sixteen patients with clinical stage III rectal
      cancer were studied. All patients underwent radical surgery after 30-Gy/10-f
      preoperative radiotherapy. Immunohistochemical examination of VEGF was performed
      on the resected tumor specimen. An immunohistochemical score established from the
      extension and intensity of the markers was used for analysis. The log-rank test
      and proportional hazards regression analysis were used to calculate the
      probability that this biomarker was associated with patient outcomes. RESULTS:
      The expression of VEGF was identified among 74.1 % (86 of 116) of patients. We
      found an increased incidence of distant metastasis (19.8 vs. 3.3 %, p = 0.039)
      and a decreased 3-year disease-free survival rate (96.7 % vs. 72.7 %, p = 0.003)
      in patients with positive VEGF staining. In multivariate survival analysis,
      positive VEGF staining (hazard ratio (HR) = 9.364, 95 % confidence interval (CI)
      1.298-71.519, p = 0.027) and ypN+ stage (HR = 2.714, 95 % CI 1.419-3.331, p =
      0.000) were the independent prognostic factors for disease-free survival.
      Subgroup analyses showed that the expression of VEGF was significantly associated
      with increased distant metastasis rate and decreased DFS in patients with ypN+
      stage. CONCLUSIONS: VEGF expression may have potential value for predicting
      distant metastasis and disease-free survival in stage III rectal cancer after 30
      Gy/10-f preoperative radiotherapy. Inhibition of VEGF in combination with
      radiotherapy may improve the patient outcomes.

PMID- 22645075
TI  - Influence of size and complexity of the hospitals in an enhanced recovery
      programme for colorectal resection.
AB  - PURPOSE: The aim of this study was to see whether the application of the enhanced
      recovery programme for colorectal resection improves the results and, in turn,
      the influence of complexity and size of the hospitals in applying this and its
      results. METHODS: A multi-centric prospective study was controlled with a
      retrospective group. The prospective operation group included 300 patients with
      elective colorectal resection due to cancer. The centres were divided depending
      on size and complexity in large reference centres (group 1) and area and basic
      general hospitals (group 2). The retrospective control group included 201
      patients with the same characteristics attended before the application of the
      programme. Completion of categories of the protocol, complications, perioperative
      mortality and stay in hospital were recorded. RESULTS: The introduction of the
      programme achieved a reduction in mortality (1 vs. 4 %), morbidity (26 vs. 39 %)
      and preoperative (<24 h vs. 3 days) and postoperative (7 vs. 11 days) stays (p <
      0.01). There was greater fulfilment of protocol in group 2 with the mean number
      of items completed at 8.46 and 60 % completed compared with the hospitals in
      group 1 (7.70 completed items and 55 % completion). The size of the hospital had
      no relation to the rate of complications (21.3 vs. 26.5 %). In smaller sized and
      less complex hospitals, the average length of stay was 1.88 days less than in
      those of greater size (6.45 vs. 8.33 days). CONCLUSION: Patients treated
      according to an enhanced recovery programme develop significantly fewer
      complications and have a shorter hospital stay. The carrying out of protocol is
      greater in smaller and less complex hospitals and is directly related to a
      shorter stay in hospital.

PMID- 22645076
TI  - Multidisciplinary management of colorectal cancer enhances access to multimodal
      therapy and compliance with National Comprehensive Cancer Network (NCCN)
      guidelines.
AB  - PURPOSE: Multidisciplinary teams have become increasingly desirable for managing
      complex disease but little objective data exist to support this approach. The aim
      of our study was to determine the impact of a multidisciplinary clinic on the
      management of colorectal cancer. METHODS: Data were prospectively collected on
      all patients with newly diagnosed colorectal cancer referred to the
      multidisciplinary clinic at our institution in 2009 and compared to a control
      group of all patients managed outside the clinic from 2008 to 2009.
      Comprehensiveness of preoperative evaluation was determined by frequency of
      abdominal and chest CT, CEA testing, and transrectal ultrasound. Access to
      multimodal care was measured by frequency of oncology consultation and treatment,
      advanced pathology testing, genetics counseling, and trial enrollment. RESULTS:
      Two hundred eighty-eight patients met inclusion criteria; 88 patients were
      referred to the clinic (40 preoperative, 48 postoperative) and 200 patients were
      managed outside. Complete preoperative evaluation was accomplished three times
      more frequently in clinic patients (85 vs. 23 %, p < 0.0001) with significant
      improvements in all parameters. Enhanced access to multimodal therapy was
      demonstrated in clinic patients by increased frequency of oncology consultation
      (98.9 vs. 61.5 %, p < 0.0001) and treatment (62.5 vs. 41.5 %, p = 0.02), advanced
      pathology testing (29.6 vs. 10.6 %, p = 0.0001), and genetics counseling (6.8 vs.
      1.6 %, p = 0.28). Clinic patients also received significantly higher rates of
      neoadjuvant therapy for stage II or greater rectal cancer (82.6 vs. 30.9 %, p =
      0.0001). CONCLUSIONS: Multidisciplinary clinic management of colorectal cancer is
      associated with a significantly more complete preoperative evaluation as well as
      improved access to multimodal therapy.

PMID- 22645077
TI  - Genetic variation in insulin pathway genes and distal colorectal adenoma risk.
AB  - BACKGROUND: Insulin, glucose, and other insulin-related proteins that mediate
      insulin signaling are associated with colorectal neoplasia risk, but associations
      with common genetic variation in insulin axis genes are less clear. In this
      study, we used a comprehensive tag single-nucleotide polymorphisms (SNPs)
      approach to define genetic variation in six insulin axis genes (IGF1, IGF2,
      IGFBP1, IGFBP3, IRS1, and IRS2) and three genes associated with estrogen
      signaling (ESR1, ESR2, and PGR). METHODS: We assessed associations between SNPs
      and distal colorectal adenoma (CRA) risk in a case-control study of 1,351
      subjects. Cases were individuals with one or more adenomas diagnosed during
      sigmoidoscopy, and controls were individuals with no adenomas at the
      sigmoidoscopy exam. We used unconditional logistic regression assuming an
      additive model to assess SNP-specific risks adjusting for multiple comparisons
      with P (act). RESULTS: Distal adenoma risk was significantly increased for one
      SNP in IGF2 [per minor allele OR = 1.41; 95 % confidence interval (CI) = 1.16,
      1.67; P (act) = 0.005] and decreased for an ESR2 SNP (per minor allele OR = 0.78;
      95 % CI = 0.66, 0.91; P (act) = 0.041). There was no statistically significant
      heterogeneity of these associations by race, sex, BMI, physical activity, or, in
      women, hormone replacement therapy use. Risk estimates did not differ in the
      colon versus rectum or for smaller (<1 cm) versus larger (>1 cm) adenomas.
      CONCLUSIONS: These data suggest that selected genetic variability in IGF2 and
      ESR2 may be modifiers of CRA risk.

PMID- 22645078
TI  - Evidence-based practices in community mental health: outcome evaluation.
AB  - In 2003, questions were being raised relating to the lack of evidence-based
      treatments available in public mental health and whether the use of treatments
      found effective in research settings would be equally effective in real world
      situations. In response, one state passed a bill mandating a disease management
      model of service delivery and the use of evidence-based practices designed to
      obtain better clinical and functional outcomes, and to maximize the possibility
      for recovery for adults experiencing a serious mental illness. The purpose of
      this article is to provide an overview of the re-engineered public mental health
      system and report on findings of a longitudinal time-series study of the
      redesigned community mental health system. Findings of the study suggest using
      evidence-based practices and following a disease management model of mental
      health service delivery can be effective in real world settings for adults
      experiencing serious mental health symptoms and functional impairment.

PMID- 22645079
TI  - A Tn antigen binding lectin from Myrsine coriacea displays toxicity in human
      cancer cell lines.
AB  - The Tn antigen (GalNAc-O-Ser/Thr) is one of the most specific human cancer
      associated structures. In the present study we characterize the biochemical and
      functional properties of the Myrsine coriacea lectin (McL). We show that McL is
      an unusual high molecular weight highly glycosylated protein, which displays a
      strong Tn binding activity. The lectin exhibits in vitro inhibition of
      proliferation in the six cancer cell lines evaluated, in a dose-dependent manner
      (the strongest activity being against HT-29 and HeLa cells), whereas it does not
      exhibit toxicity against normal lymphocytes. McL could be exploited in the design
      of potential new tools for the diagnosis or treatment of cancer.

PMID- 22645081
TI  - Unveiling the beauty of Archaea.

PMID- 22645080
TI  - Protein tyrosine phosphatase 1B inhibitory activity of Indonesian herbal
      medicines and constituents of Cinnamomum burmannii and Zingiber aromaticum.
AB  - We screened water and methanol extracts of 28 Indonesian medicinal plants for
      their protein tyrosine phosphatase 1B (PTP1B) inhibitory activities. Nine water
      extracts, i.e., Alstonia scholaris leaf, Blumea balsamifera, Cinnamomum
      burmannii, Cymbopogon nardus, Melaleuca leucadendra, Phyllanthus niruri, Piper
      nigrum, Syzygium aromaticum, and Sy. polyanthum, exhibited >=70 % inhibition at
      25 MUg/mL, whereas 11 methanol extracts, i.e., Als. scholaris, Andrographis
      paniculata, B. balsamifera, Ci. burmannii, Curcuma heyneana, Glycyrrhiza glabra,
      M. leucadendra, Punica granatum, Rheum palmatum, Sy. polyanthum, and Z.
      aromaticum, exhibited >=70 % inhibition at 25 MUg/mL. Water extracts of B.
      balsamifera (IC50, 2.26 MUg/mL) and M. leucadendra (IC50, 2.05 MUg/mL), and
      methanol extracts of Ci. burmannii (IC50, 2.47 MUg/mL), Pu. granatum (IC50, 2.40
      MUg/mL), and Sy. polyanthum (IC50, 1.03 MUg/mL) exhibited strong inhibitory
      activity, which was comparable with that of the positive control, RK-682 (IC50,
      2.05 MUg/mL). The PTP1B inhibitory activity of the constituents of Ci. burmannii
      and Z. aromaticum was then evaluated. 5'-Hydroxy-5-hydroxymethyl-4",5"
      methylenedioxy-1,2,3,4-dibenzo-1,3,5-cycloheptatriene (2; IC50, 29.7 MUM) and
      trans-cinnamaldehyde (5; IC50, 57.6 MUM) were the active constituents of Ci.
      burmannii, while humulatrien-5-ol-8-one (21; IC50, 27.7 MUM), kaempferol-3,4'-di
      O-methyl ether (32; IC50, 17.5 MUM), and (S)-6-gingerol (33; IC50, 28.1 MUM) were
      those of Z. aromaticum. These results suggest that these medicinal plants may
      contribute to the treatment and/or prevention of type II diabetes and/or obesity
      through PTP1B inhibition.

PMID- 22645082
TI  - Archaeal chromatin proteins.
AB  - Archaea, along with Bacteria and Eukarya, are the three domains of life. In all
      living cells, chromatin proteins serve a crucial role in maintaining the
      integrity of the structure and function of the genome. An array of small,
      abundant and basic DNA-binding proteins, considered candidates for chromatin
      proteins, has been isolated from the Euryarchaeota and the Crenarchaeota, the two
      major phyla in Archaea. While most euryarchaea encode proteins resembling
      eukaryotic histones, crenarchaea appear to synthesize a number of unique DNA
      binding proteins likely involved in chromosomal organization. Several of these
      proteins (e.g., archaeal histones, Sac10b homologs, Sul7d, Cren7, CC1, etc.) have
      been extensively studied. However, whether they are chromatin proteins and how
      they function in vivo remain to be fully understood. Future investigation of
      archaeal chromatin proteins will lead to a better understanding of chromosomal
      organization and gene expression in Archaea and provide valuable information on
      the evolution of DNA packaging in cellular life.

PMID- 22645083
TI  - Rapid progress of DNA replication studies in Archaea, the third domain of life.
AB  - Archaea, the third domain of life, are interesting organisms to study from the
      aspects of molecular and evolutionary biology. Archaeal cells have a unicellular
      ultrastructure without a nucleus, resembling bacterial cells, but the proteins
      involved in genetic information processing pathways, including DNA replication,
      transcription, and translation, share strong similarities with those of
      Eukaryota. Therefore, archaea provide useful model systems to understand the more
      complex mechanisms of genetic information processing in eukaryotic cells.
      Moreover, the hyperthermophilic archaea provide very stable proteins, which are
      especially useful for the isolation of replisomal multicomplexes, to analyze
      their structures and functions. This review focuses on the history, current
      status, and future directions of archaeal DNA replication studies.

PMID- 22645084
TI  - Cellular and organellar membrane-associated proteins in haloarchaea: perspectives
      on the physiological significance and biotechnological applications.
AB  - Halophilic archaea (haloarchaea) inhabit hypersaline environments, tolerating
      extreme salinity, low oxygen and nutrient availability, and in some cases, high
      pH (soda lakes) and irradiation (saltern ponds). Membrane-associated proteins of
      haloarchaea, such as surface layer (S-layer) proteins, transporters, retinal
      proteins, and internal organellar membrane proteins including intracellular gas
      vesicle proteins and those associated with polyhydroxyalkanoate (PHA) granules,
      contribute greatly to their environmental adaptations. This review focuses on
      these haloarchaeal cellular and organellar membrane-associated proteins, and
      provides insight into their physiological significance and biotechnological
      potential.

PMID- 22645085
TI  - Psychrotolerant methanogenic archaea: diversity and cold adaptation mechanisms.
AB  - Because of their diversity and abundance in a wide range of environments,
      particularly in cold regions, cold-adaptive archaea are expected to play a
      pivotal role in material recycling in cold environments. Methanogenic archaea are
      ubiquitous on earth and produce a large amount of methane (CH(4)) as their main
      carbon metabolite. Methanogens are the most laboratory amendable archaea. The few
      psychrophilic archaea that have been cultured to date are mainly affiliated with
      methanogens, thus make them a good model for investigating mechanisms of archaeal
      cold adaptation. Studies of psychrotolerant methanogens have been ongoing since
      the 1990s. Using Methanococcoides burtonii, a methanogen isolated from Ace Lake
      in Antarctica, extensive studies on the genomic characteristics associated with
      cold adaptation have been carried out by the Cavicchioli laboratory. We recently
      analyzed the genome of another psychrophilic methanogen and identified the gene
      repertoire associated with cold adaptation. This review summarizes recent studies
      of psychroactive methanogens, particularly their diversity, the genomics and
      proteomics associated with their cold adaptation, and the cellular components and
      proteins likely involved in their cold protection.

PMID- 22645086
TI  - Archaeal viruses--novel, diverse and enigmatic.
AB  - Recent research has revealed a remarkable diversity of viruses in archaeal-rich
      environments where spindles, spheres, filaments and rods are common, together
      with other exceptional morphotypes never recorded previously. Moreover, their
      double-stranded DNA genomes carry very few genes exhibiting homology to those of
      bacterial and eukaryal viruses. Studies on viral life cycles are still at a
      preliminary stage but important insights are being gained especially from
      microarray analyses of viral transcripts for a few model virus-host systems.
      Recently, evidence has been presented for some exceptional archaeal-specific
      mechanisms for extra-cellular morphological development of virions and for their
      cellular extrusion. Here we summarise some of the recent developments in this
      rapidly developing and exciting research area.

PMID- 22645088
TI  - Relationship between triphasic mechanical properties of articular cartilage and
      osteoarthritic grade.
AB  - The purpose of this study was to explore the triphasic mechanical properties of
      osteoarthritic cartilage with different pathological grades. First, samples of
      cartilage from rabbits with different stages of osteoarthritis (OA) were graded.
      Following this, the cartilage was strained by a swelling experiment, and changes
      were measured using a high-frequency ultrasound system. The result, together with
      fixed charge density and water volume fraction of cartilage samples, was used to
      estimate the uniaxial modulus of the cartilage tissue, based on a triphasic
      model. For the control cartilage samples, the uniaxial elastic modulus on the
      cartilage surface was lower than those in the middle and deep layers. With an
      increase in the OA grade, the uniaxial elastic modulus of the surface, middle and
      deep layers decreased. A significant difference was found in the surface elastic
      modulus of different OA grades (P<0.01), while no significant differences were
      identified for OA cartilages of Grades 1 and 2 in the middle and deep layers
      (P<0.01). Compared with Grades 1 and 2, there was a significant reduction in the
      elastic modulus in the middle and deep layers of Grade 3 OA cartilage (P<0.05).
      Overall, this study may provide a new quantitative method to evaluate the
      severity of OA using the mechanical properties of cartilage tissue.

PMID- 22645087
TI  - The role of Eph receptors in lens function and disease.
AB  - Cataract is the single largest contributor to blindness in the world, with the
      disease having a strong genetic component. In recent years the Eph family of
      receptor tyrosine kinases has been identified as a key regulator in lens clarity.
      In this review we discuss the roles of the Eph receptors in lens biology and
      cataract development.

PMID- 22645089
TI  - De novo characterization of the root transcriptome of a traditional Chinese
      medicinal plant Polygonum cuspidatum.
AB  - Various active components have been extracted from the root of Polygonum
      cuspidatum. However, the genetic basis for their activity is virtually unknown.
      In this study, 25600002 short reads (2.3 Gb) of P. cuspidatum root transcriptome
      were obtained via Illumina HiSeq 2000 sequencing. A total of 86418 unigenes were
      assembled de novo and annotated. Twelve, 18, 60 and 54 unigenes were respectively
      mapped to the mevalonic acid (MVA), methyl-D-erythritol 4-phosphate (MEP),
      shikimate and resveratrol biosynthesis pathways, suggesting that they are
      involved in the biosynthesis of pharmaceutically important anthraquinone and
      resveratrol. Eighteen potential UDP-glycosyltransferase unigenes were identified
      as the candidates most likely to be involved in the biosynthesis of glycosides of
      secondary metabolites. Identification of relevant genes could be important in
      eventually increasing the yields of the medicinally useful constituents of the P.
      cuspidatum root. From the previously published transcriptome data of 19 non-model
      plant taxa, 1127 shared orthologs were identified and characterized. This
      information will be very useful for future functional, phylogenetic and
      evolutionary studies of these plants.

PMID- 22645091
TI  - A novel relay method for determining low-clearance values.
AB  - A novel relay method has been developed using cryopreserved human hepatocytes to
      measure intrinsic clearance of low-clearance compounds. The relay method involved
      transferring the supernatant from hepatocyte incubations to freshly thawed
      hepatocytes at the end of the 4-h incubation to prolong the exposure time to
      active enzymes in hepatocytes. An accumulative incubation time of 20 h or longer
      in hepatoctyes can be achieved using the method. The relay method was validated
      using seven commercial drugs (diazepam, disopyramide, theophylline, timolol,
      tolbutamide, S-warfarin, and zolmitriptan) that were metabolized by various
      cytochrome P450s with low human in vivo intrinsic clearance at approximately 2 to
      15 ml . min-1 . kg-1. The results showed that the relay method produced excellent
      predictions of human in vivo clearance. The difference between in vitro and in
      vivo intrinsic clearance was within 2-fold for most compounds, which is similar
      to the standard prediction accuracy for moderate to high clearance compounds
      using hepatocytes. The relay method is a straightforward, relatively low cost,
      and easy-to-use new tool to address the challenges of low clearance in drug
      discovery and development.

PMID- 22645090
TI  - Importance of liver biopsy findings in immunosuppression management: biopsy
      monitoring and working criteria for patients with operational tolerance.
AB  - Obstacles to morbidity-free long-term survival after liver transplantation (LT)
      include complications of immunosuppression (IS), recurrence of the original
      disease and malignancies, and unexplained chronic hepatitis and graft fibrosis.
      Many programs attempt to minimize chronic exposure to IS by reducing dosages and
      stopping steroids. A few programs have successfully weaned a highly select group
      of recipients from all IS without apparent adverse consequences, but long-term
      follow-up is limited. Patients subjected to adjustments in IS are usually
      followed by serial liver chemistry tests, which are relatively insensitive
      methods for detecting allograft damage. Protocol biopsy has largely been
      abandoned for hepatitis C virus-negative recipients, at least in part because of
      the inability to integrate routine histopathological findings into a rational
      clinical management algorithm. Recognizing a need to more precisely categorize
      and determine the clinical significance of findings in long-term biopsy samples,
      the Banff Working Group on Liver Allograft Pathology has reviewed the literature,
      pooled the experience of its members, and proposed working definitions for biopsy
      changes that (1) are conducive to lowering IS and are compatible with operational
      tolerance (OT) and (2) raise concern for closer follow-up and perhaps increased
      IS during or after IS weaning. The establishment of guidelines should help us to
      standardize analyses of the effects of various treatments and/or weaning
      protocols and more rigorously categorize patients who are assumed to show OT.
      Long-term follow-up using standardized criteria will help us to determine the
      consequences of lowering IS and to define and determine the incidence and
      robustness of OT in liver allografts.

PMID- 22645092
TI  - Selective mechanism-based inactivation of CYP3A4 by CYP3cide (PF-04981517) and
      its utility as an in vitro tool for delineating the relative roles of CYP3A4
      versus CYP3A5 in the metabolism of drugs.
AB  - CYP3cide (PF-4981517; 1-methyl-3-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-4
      [(3S)-3-piperidin-1-ylpyrrolidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine) is a potent,
      efficient, and specific time-dependent inactivator of human CYP3A4. When
      investigating its inhibitory properties, an extreme metabolic inactivation
      efficiency (k(inact)/K(I)) of 3300 to 3800 ml . min-1 . MUmol-1 was observed
      using human liver microsomes from donors of nonfunctioning CYP3A5 (CYP3A5 *3/*3).
      This observed efficiency equated to an apparent K(I) between 420 and 480 nM with
      a maximal inactivation rate (k(inact)) equal to 1.6 min-1. Similar results were
      achieved with testosterone, another CYP3A substrate, and other sources of the
      CYP3A4 enzyme. To further illustrate the abilities of CYP3cide, its partition
      ratio of inactivation was determined with recombinant CYP3A4. These studies
      produced a partition ratio approaching unity, thus underscoring the inactivation
      capacity of CYP3cide. When CYP3cide was tested at a concentration and
      preincubation time to completely inhibit CYP3A4 in a library of genotyped
      polymorphic CYP3A5 microsomes, the correlation of the remaining midazolam 1'
      hydroxylase activity to CYP3A5 abundance was significant (R2 value equal to 0.51,
      p value of <0.0001). The work presented here supports these findings by fully
      characterizing the inhibitory properties and exploring CYP3cide's mechanism of
      action. To aid the researcher, multiple commercially available sources of
      CYP3cide were established, and a protocol was developed to quantitatively
      determine CYP3A4 contribution to the metabolism of an investigational compound.
      Through the establishment of this protocol and the evidence provided here, we
      believe that CYP3cide is a very useful tool for understanding the relative roles
      of CYP3A4 versus CYP3A5 and the impact of CYP3A5 genetic polymorphism on a
      compound's pharmacokinetics.

PMID- 22645093
TI  - The use of ultrasonography to study teratogenicity in ruminants: evaluation of
      Ipomoea carnea in goats.
AB  - BACKGROUND: Ipomoea carnea (I. carnea) is a poisonous plant found in Brazil and
      other tropical countries that often poison livestock. The plant contains the
      alkaloids calystegines and mainly swainsonine, which inhibit cellular enzymes and
      cause systematic cell death. The objective of this study was to evaluate the
      perinatal effects of I. carnea in goats. METHODS: Forty-seven pregnant goats were
      randomly allocated into 5 treatment groups and given the following doses (g/kg
      BW) of I. carnea: 0 (IC0), 1.0 (IC1), 3.0 (IC3), 5.0 (IC5) and 7.5 (IC7). The
      treatment animals were given fresh I. carnea from day 27 of gestation to
      parturition. Weight gains and serum biochemistry were evaluated. Fetuses were
      evaluated using ultrasonographic measurements. RESULTS: Goats from the IC7 group
      showed clinical signs of poisoning. Ultrasound examination revealed that I.
      carnea feeding in all treatment groups reduced fetal movement compared to the
      controls. There was an increase in the total number of birth defects
      (retrognathia and arthrogyposis) in the IC7 and IC5 groups compared to the
      controls. CONCLUSION: The results show that I. carnea has teratogenic potential
      in goats. In addition, ultrasounds were useful in evaluating fetotoxicity and
      teratogenicity.

PMID- 22645094
TI  - Impact of a school-based sexual abuse prevention education program on the
      knowledge and attitude of high school girls.
AB  - Sexual abuse has been considered a public health issue because of the various
      health implications resulting from it. The school nurse has a responsibility in
      assisting the high school girl to prevent victimization. This study adopted a
      quasi-experimental design in which a sexual abuse prevention education package
      was developed and used to educate high school girls in a selected school in
      Nigeria. Evaluation of the impact of the package revealed a significant increase
      in the knowledge mean scores of the girls at first postintervention stage and
      this increase was maintained at second postintervention stage. No significant
      shift was observed for the attitude of the girls. Education is a significant tool
      that could be used in improving the knowledge of sexual abuse prevention among
      high school girls, but attitude supporting sexual abuse prevention can only be
      improved when myths of sexual abuse are corrected in the larger society.

PMID- 22645095
TI  - 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) evaluation of
      nodular lesions in patients with Neurofibromatosis type 1 and plexiform
      neurofibromas (PN) or malignant peripheral nerve sheath tumors (MPNST).
AB  - BACKGROUND: Individuals with Neurofibromatosis type 1 (NF1) are at risk for
      developing malignant peripheral nerve sheath tumors (MPNST), which frequently
      arise in preexisting plexiform neurofibromas (PN). Magnetic resonance imaging
      (MRI) with volumetric analysis and 18-fluorodeoxyglucose-positron emission
      tomography (FDG-PET) were utilized to monitor symptomatic nodular lesions.
      PROCEDURE: Patients with NF1 and PN on a NCI natural history trial were monitored
      for total body tumor volume (TTV) using volumetric MRI. FDG-PET was performed in
      individuals with a nodular well-demarcated lesion >=3 cm if they were growing,
      painful, or there was a prior history of MPNST (target lesions). Asymptomatic
      nodular lesions were evaluated as non-target lesions. RESULTS: Fifteen patients
      (8m, 7f) median age of 18.3 years (range, 10-45 years) had a single target and
      non-target (n = 46) nodular lesions identified on MRI. Target lesions arose
      within (n = 8) or outside (n = 3) a PN, and all but 1 had increased FDG uptake.
      FDG uptake was increased in non-target lesions but to a lesser degree. FDG uptake
      in the surrounding PN was low, similar to background activity. Pathologic
      evaluation performed in 11 patients demonstrated neurofibroma (n = 6), atypical
      neurofibroma (n = 2) and malignancy (n = 3). CONCLUSIONS: Nodular target lesions
      identified on MRI in individuals with NF1 and PN demonstrate increased FDG uptake
      similar to MPNST, but may be benign on biopsy. Nodular target lesions may be at
      greater risk for malignant transformation, but their biologic and clinical
      behavior has not been well studied. Careful longitudinal evaluation will be
      required to better understand the malignant potential of these lesions.

PMID- 22645097
TI  - The effects of domestication on the scaling of below- vs. aboveground biomass in
      four selected wheat (Triticum; Poaceae) genotypes.
AB  - PREMISE OF THE STUDY: Theory and empirical studies have shown that, on average,
      belowground biomass (M(B)) scales one-to-one (isometrically) with aboveground
      biomass (M(A)) within and across plant species both at the individual and
      population level, i.e., M(B) ? M(A)(alpha=1), where alpha is the scaling
      exponent. However, little is known about how domestication affects this
      relationship. METHODS: To examine the effects of domestication, we investigated
      the root vs. shoot biomass relationship during the first 30 d of growth of four
      wheat genotypes: two older genotypes, MO4 (T. monococcum, a diploid) and DM31 (T.
      dicoccum, a tetraploid) and two more recent genotypes, DX24 and L8275 (T.
      aestivum, both hexaploids). RESULTS: Biomass allocation to roots scaled more or
      less isometrically with respect to shoot biomass allocation during the first 30 d
      of growth for both of the older genotypes, whereas shoot biomass allocation
      exceeded root allocation for the two more recent genotypes. This difference was
      attributable to the first 15 d of growth. Although root biomass allocation
      exceeded shoot biomass allocation during the first 15 d of growth for the two
      older genotypes, shoot biomass exceeded root biomass allocation during this
      critical phase of development for the two more recent genotypes. CONCLUSIONS:
      Based on a very limited sample of wheat genotypes, these results indicate that
      domestication has resulted in an increased biomass allocation to shoots compared
      to root biomass allocation. This shift possibly reflects artificial selection
      under agricultural conditions (for which water and nutrients are not limiting)
      favoring higher crop yields.

PMID- 22645098
TI  - A reference microsatellite kit to assess for genetic diversity of Sorghum bicolor
      (Poaceae).
AB  - PREMISE OF THE STUDY: Discrepancies in terms of genotyping data are frequently
      observed when comparing simple sequence repeat (SSR) data sets across genotyping
      technologies and laboratories. This technical concern introduces biases that
      hamper any synthetic studies or comparison of genetic diversity between
      collections. To prevent this for Sorghum bicolor, we developed a control kit of
      48 SSR markers. METHODS AND RESULTS: One hundred seventeen markers were selected
      along the genome to provide coverage across the length of all 10 sorghum linkage
      groups. They were tested for polymorphism and reproducibility across two
      laboratories (Centre de Cooperation Internationale en Recherche Agronomique pour
      le Developpement [CIRAD], France, and International Crops Research Institute for
      the Semi-Arid Tropics [ICRISAT], India) using two commonly used genotyping
      technologies (polyacrylamide gel-based technology with LI-COR sequencing machines
      and capillary systems with ABI sequencing apparatus) with DNA samples from a
      diverse set of 48 S. bicolor accessions. CONCLUSIONS: A kit for diversity
      analysis (http://sat.cirad.fr/sat/sorghum_SSR_kit/) was developed. It contains
      information on 48 technically robust sorghum microsatellite markers and 10 DNA
      controls. It can further be used to calibrate sorghum SSR genotyping data
      acquired with different technologies and compare those to genetic diversity
      references.

PMID- 22645096
TI  - The evolutionary history of the white-rayed species of Melampodium (Asteraceae)
      involved multiple cycles of hybridization and polyploidization.
AB  - PREMISE OF THE STUDY: Polyploidy plays an important role in race differentiation
      and eventually speciation. Underlying mechanisms include chromosomal and genomic
      changes facilitating reproductive isolation and/or stabilization of hybrids. A
      prerequisite for studying these processes is a sound knowledge on the origin of
      polyploids. A well-suited group for studying polyploid evolution consists of the
      three species of Melampodium ser. Leucantha (Asteraceae): M. argophyllum, M.
      cinereum, and M. leucanthum. METHODS: The origin of polyploids was inferred using
      network and tree-based phylogenetic analyses of several plastid and nuclear DNA
      sequences and of fingerprint data (AFLP). Genome evolution was assessed via
      genome size measurements, karyotype analysis, and in situ hybridization of
      ribosomal DNA. KEY RESULTS: Tetraploid cytotypes of the phylogenetically distinct
      M. cinereum and M. leucanthum had, compared to the diploid cytotypes, doubled
      genome sizes and no evidence of gross chromosomal rearrangements. Hexaploid M.
      argophyllum constituted a separate lineage with limited intermixing with the
      other species, except in analyses from nuclear ITS. Its genome size was lower
      than expected if M. cinereum and/or M. leucanthum were involved in its origin,
      and no chromosomal rearrangements were evident. CONCLUSIONS: Polyploids in M.
      cinereum and M. leucanthum are of recent autopolyploid origin in line with the
      lack of significant genomic changes. Hexaploid M. argophyllum also appears to be
      of autopolyploid origin against the previous hypothesis of an allopolyploid
      origin involving the other two species, but some gene flow with the other species
      in early phases of differentiation cannot be excluded.

PMID- 22645099
TI  - Virus infections in wild plant populations are both frequent and often
      unapparent.
AB  - PREMISE OF THE STUDY: Pathogens are thought to regulate host populations. In
      agricultural crops, virus infection reduces yield. However, in wild plants little
      is known about the spatial and temporal patterns of virus prevalence. Thus,
      pathogen effects on plant population dynamics are unclear. Prevalence data
      provide necessary background for (1) evaluating the effects of virus infection on
      plant population size and dynamics and (2) improving risk assessment of virus
      resistant transgenic crops. METHODS: We used ELISA and RT-PCR to survey wild
      Cucurbita pepo populations over 4 years for five viruses, aphid-transmitted
      viruses of the genus Potyvirus as a group and PCR to survey for virus-resistance
      transgenes. In addition, we surveyed the literature for reports of virus
      prevalence in wild populations. KEY RESULTS: In 21 C. pepo populations, virus
      prevalence (0-74%) varied greatly among populations, years, and virus species. In
      samples analyzed by both ELISA and RT-PCR, RT-PCR detected 6-44% more viruses
      than did ELISA. Eighty percent of these infections did not cause any visually
      apparent symptoms. In our samples, the virus-resistance transgene was not
      present. In 30 published studies, 92 of 146 tested species were infected with
      virus, and infection rates ranged from 0.01-100%. Most published studies used
      ELISA, suggesting virus prevalence is higher than reported. CONCLUSIONS: In wild
      C. pepo, the demographic effects of virus are likely highly variable in space and
      time. Further, our literature survey suggests that such variation is probably
      common across plant species. Our results indicate that risk assessments for virus
      resistant transgenic crops should not rely on visual symptoms or ELISA and should
      include data from multiple populations over multiple years.

PMID- 22645100
TI  - The patient-centered medical home: a review of recent research.
AB  - The patient-centered medical home is an important innovation in health care
      delivery. There is a need to assess the scope and substance of published research
      on medical homes. This article reviews published evaluations of medical home care
      for the period 2007 to 2010. Chief findings from these evaluations as a whole
      include associations between the provision of medical home care and improved
      quality, in addition to decreased utilization associated with medical home care
      in high-cost areas such as emergency department use. However, fewer associations
      were found across evaluations between medical home care and enhanced patient or
      family experiences. The early medical home research appears to reflect both the
      wide variation in how medical homes are being designed and implemented in
      practice and in how researchers are choosing to evaluate patient-centered medical
      home design and implementation. While some aspects of medical home care show
      promise, continued evolution of medical home evaluative research is needed.

PMID- 22645101
TI  - A rare cause of cardiac decompensation in a patient with left ventricular
      hypertrophy.

PMID- 22645102
TI  - The role of endovascular expertise in carotid artery stenting: results from the
      ALKK-CAS-Registry in 5,535 patients.
AB  - PURPOSE: Several scientific committees have proposed an accentuation of operator
      minimal requirements before accreditation for carotid artery stenting is granted.
      The current study aims to identify potential effects from increasing site
      experience on periprocedural safety and outcome of carotid artery stenting (CAS).
      METHODS: Between 1996 and December 2009, 5,535 procedures have been entered into
      the prospective, controlled ALKK-CAS-Registry. The total cohort was divided in
      four subgroups according to the consecutive patient order at each participating
      center: patients 1-49 (n = 1,485), 50-99 (n = 1,118), 100-199 (n = 1,521) and
      >=200 (n = 1,411). RESULTS: The median age of all patients was 71 years; 52.8 %
      had a symptomatic carotid stenosis. A decline in the rates of in-hospital major
      stroke (2.1, 1.9, 1.6, 0.9, p for trend 0.014) and of ipsilateral strokes (3.1,
      2.4, 2.5, 1.6 %, p for trend 0.019) was substantiated with increasing site
      experience. This significant trend was preserved in the combined rate of major
      stroke and death (4.0, 3.2, 3.4, 2.4 %, p for trend 0.034). Apart from CAS
      experience, improvements in CAS technique, a decreasing number of symptomatic
      patients and an increasing number of procedures under embolic protection (each p
      for trend <0.05) might have contributed to these results. CONCLUSIONS: The
      results show a gradual reduction of in-hospital stroke rates with increasing
      center experience. Extensive supervision of CAS learners and further promotion of
      proctorship programs seem to be essential.

PMID- 22645103
TI  - A retrospective study of nurse-assisted propofol sedation in patients with
      amyotrophic lateral sclerosis undergoing percutaneous endoscopic gastrostomy.
AB  - BACKGROUND: Percutaneous endscopic gastrostomy (PEG) placement is standard in the
      care of patients with amyotrophic lateral sclerosis (ALS) unable to maintain
      adequate oral nutrition. This has been performed using conscious sedation with
      narcotics/benzodiazepines. However, recent studies suggest that propofol sedation
      is superior for other endoscopic procedures. In addition, endoscopic PEG
      placement is not recommended for patients with ALS with a forced vital capacity
      (FVC) <50%. The authors postulated that nurse-administered propofol sedation
      (NAPS) with the addition of bilevel positive airway pressure (BiPAP) would be
      superior to standard sedation with midazolam/fentanyl (M/F) in all patients with
      ALS regardless of FVC. Here the authors review their retrospective experience of
      PEG placements in patients with ALS using propofol +/- BiPAP vs traditional
      sedation +/- BiPAP. RESULTS: Thirty-one patients received M/F, and 29 received
      NAPS. BiPAP was used more often in the NAPS group (24/29 NAPS vs 6/31 M/F
      respectively, P < .0001). Twenty-nine of 31 PEG placements in the M/F group and
      27 of 29 PEG placements in the NAPS group were successful. Seven desaturation
      events occurred to <90% in the M/F group compared with 1 desaturation event in
      the NAPS group (P = .05). No other complications were noted. CONCLUSION: PEG
      placement can be performed safely in patients with ALS with FVC <50% using NAPS
      with BiPAP.

PMID- 22645104
TI  - Which is more effective to prevent enteral nutrition-related complications, high-
      or medium-viscosity thickened enteral formula in patients with percutaneous
      endoscopic gastrostomy?: a single-center retrospective chart review.
AB  - BACKGROUND: Administration of thickened enteral formula (TEF) through a
      percutaneous endoscopic gastrostomy (PEG) tube is becoming a common practice in
      Japan to prevent enteral nutrition (EN)-related complications. However, what
      constitutes an adequate viscosity of TEF remains unclear. The aim of this study
      was to examine the clinical effects of TEFs with different viscosities
      administered through PEG. METHODS: The subjects were 50 patients admitted to a
      single institution who underwent PEG placement. Viscosities of TEFs frequently
      administered to the patients were measured, and EN-related complications,
      nutrition intakes, and clinical outcomes were compared between high- and medium
      viscosity TEFs during the first 2 weeks after TEF feeding initiation. RESULTS:
      The measured viscosities of high- and medium-viscosity TEFs were 10,382 +/- 931
      and 3492 +/- 296 mPa.s, respectively. Protein and fluid intakes with TEF were
      significantly less in the high-viscosity group. There was no significant
      difference in EN-related complications, energy intakes, or clinical outcomes
      between high- and medium-viscosity TEFs. CONCLUSION: In this study, high
      viscosity TEFs showed no statistical difference in either EN-related
      complications or clinical outcomes, in comparison with medium-viscosity TEF.

PMID- 22645105
TI  - Overweight and obesity prevalence and determinants in Italy: an update to 2010.
AB  - PURPOSE: To provide updated information on trends and determinants of
      underweight, overweight, and obesity in Italian adults. METHODS: We considered
      data from 5 surveys conducted annually between 2006 and 2010, on a total of
      14,135 subjects aged 18 years or more (6,834 men and 7,301 women), representative
      of the Italian adult population, including self-reported information on height
      and weight. RESULTS: Overall, 3.1 % of the Italian adult population was
      underweight (body mass index, BMI, <18.5 kg/m(2); 0.8 % men, 5.3 % women), 31.8 %
      overweight (25<= BMI <30 kg/m(2); 39.8 % men, 24.4 % women), and 8.9 % obese (BMI
      >=30 kg/m(2); 8.5 % men, 9.4 % women). We observed no specific pattern of
      overweight/obesity across calendar years in men (multivariate prevalence ratios,
      PR, for 2010 vs 2006: 0.95; p for trend: 0.980) and a non-significant decreased
      trend in women (PR: 0.92; p for trend: 0.051). Prevalence of overweight/obesity
      significantly increased with age (PRs for >=65 vs 18-24 years: 2.01 in men, 2.65
      in women), decreased with education (PRs for high vs low education: 0.79 in men,
      0.54 in women), and was less frequent in single than in married adults (PRs: 0.85
      in men, 0.78 in women). Overweight/obesity was significantly more frequent in
      adults from southern versus northern Italy (PRs: 1.13 in men, 1.32 in women) and
      in former versus never smokers (PRs: 1.23 in men, 1.19 in women). CONCLUSIONS: In
      Italy, we did not find unfavorable trends in overweight and obesity prevalence
      across calendar years. However, there are specific subgroups of the population
      with elevated prevalence of overweight and obesity, mainly adults from southern
      Italy and less educated ones.

PMID- 22645106
TI  - De-alcoholised white and red wines decrease inflammatory markers and NF-kappaB in
      atheroma plaques in apoE-deficient mice.
AB  - AIMS OF THE STUDY: Wine polyphenols attenuate the development of atherosclerosis,
      which involves an inflammatory process. We studied the beneficial effect of de
      alcoholised white and red wines (DWW and DRW, respectively) on the development of
      atheroma plaques and on the expression of biomarkers. METHODS: We administered
      control or de-alcoholised wine-rich diets to apoE-deficient mice for 12 or 20
      weeks. We then used optical microscopy or immunofluorescence to examine
      atherosclerotic lesion development in the thoracic aorta and aortic root and
      assessed the presence of cytokines and adhesion molecules by qPCR and
      immunofluorescence in total aorta and aortic root, respectively. RESULTS:
      Atherosclerotic lesions in thoracic aorta were significantly decreased in mice
      supplemented with DWW (30 %) and DRW (62 %) for 20 weeks. In addition, the
      expressions of interferon-gamma, interleukin-1beta, the monocyte chemoattractant
      protein-1 and CD68 were reduced by DRW. The adhesion molecule P-selectin,
      vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 were
      decreased by 52, 76 and 45 %, respectively, in mice fed DRW for 12 weeks, whereas
      DWW reduced these parameters in a minor extent. The NF-kappaB expression in total
      aorta was significantly decreased in the mice treated with de-alcoholised wines
      for 12 weeks. CONCLUSIONS: DRW is shown to be more effective than DWW on
      cytokines and adhesion molecule expression, in the early stages of the
      inflammatory events associated with atherosclerosis development, probably due to
      the high phenolic content of red wine. Downregulation of NF-kappaB expression may
      be involved in the mechanism by which de-alcoholised wines modulate
      atherosclerosis.

PMID- 22645108
TI  - Resting state changes in functional connectivity correlate with movement recovery
      for BCI and robot-assisted upper-extremity training after stroke.
AB  - BACKGROUND: Robot-assisted training may improve motor function in some
      hemiparetic patients after stroke, but no physiological predictor of
      rehabilitation progress is reliable. Resting state functional magnetic resonance
      imaging (RS-fMRI) may serve as a method to assess and predict changes in the
      motor network. OBJECTIVE: The authors examined the effects of upper-extremity
      robot-assisted rehabilitation (MANUS) versus an electroencephalography-based
      brain computer interface setup with motor imagery (MI EEG-BCI) and compared
      pretreatment and posttreatment RS-fMRI. METHODS: In all, 9 adults with upper
      extremity paresis were trained for 4 weeks with a MANUS shoulder-elbow robotic
      rehabilitation paradigm. In 3 participants, robot-assisted movement began if no
      voluntary movement was initiated within 2 s. In 6 participants, MI-BCI-based
      movement was initiated if motor imagery was detected. RS-fMRI and Fugl-Meyer (FM)
      upper-extremity motor score were assessed before and after training. RESULTS: .
      The individual gain in FM scores over 12 weeks could be predicted from functional
      connectivity changes (FCCs) based on the pre-post differences in RS-fMRI
      measurements. Both the FM gain and FCC were numerically higher in the MI-BCI
      group. Increases in FC of the supplementary motor area, the contralesional and
      ipsilesional motor cortex, and parts of the visuospatial system with mostly
      association cortex regions and the cerebellum correlated with individual upper
      extremity function improvement. CONCLUSION: FCC may predict the steepness of
      individual motor gains. Future training could therefore focus on directly
      inducing these beneficial increases in FC. Evaluation of the treatment groups
      suggests that MI is a potential facilitator of such neuroplasticity.

PMID- 22645107
TI  - Evidence of altered biochemical composition in the hearts of adult intrauterine
      growth-restricted rats.
AB  - PURPOSE: Epidemiological studies clearly link intrauterine growth restriction
      with increased risk of cardiac disease in adulthood. The mechanisms leading to
      this increased risk are poorly understood; remodeling of the myocardium is
      implicated. The aim was to determine the effect of early life growth restriction
      on the biochemical composition of the left ventricular myocardium in adult rats.
      METHODS: Wistar Kyoto dams were fed either a low protein diet (LPD; 8.7 % casein)
      or normal protein diet (NPD; 20 % casein) during pregnancy and lactation; from
      weaning, the offspring were fed normal rat chow. At 18 weeks of age, the
      biochemical composition of the hearts of NPD control (n = 9) and LPD intrauterine
      growth-restricted (n = 7) offspring was analyzed using Fourier Transform Infrared
      (FTIR) micro-spectroscopy. RESULTS: Body weights at postnatal day 4 were
      significantly lower and remained lower throughout the experimental period in the
      LPD offspring compared to controls. FTIR analysis of the infrared absorption
      spectra across the whole "fingerprint" region (1,800-950 cm(-1)) demonstrated
      wider variation in absorbance intensity in the LPD group compared to controls. In
      particular, there were marked differences detected in the protein (1,540 cm(-1)),
      lipid (1,455 and 1,388 cm(-1)), proteoglycan (1,228 cm(-1)) and carbohydrate
      (1,038 cm(-1)) bands, indicating increased lipid, proteoglycan and carbohydrate
      content in the growth-restricted myocardium. CONCLUSION: In conclusion, changes
      in the biochemical composition of the myocardium provide a likely mechanism for
      the increased vulnerability to cardiovascular disease in offspring that were
      growth restricted in early life.

PMID- 22645109
TI  - Caspase inhibitors: prospective therapies for stroke.
AB  - In ischemic stroke, apoptosis persists for days to weeks after the onset of an
      ischemic event. Cysteine-ASPartic proteASEs (caspases) are key mediators of
      apoptosis and neurodegeneration in stroke. The impact of caspase activity is not
      restricted to neuronal death, as caspases can exacerbate inflammation and alter
      glial function. Thus, caspases are logical therapeutic targets for this disease,
      but they have never been clinically evaluated due to a paucity of ideal drug
      candidates. Recent developments in caspase inhibition and drug delivery offer
      novel neuroprotective strategies for stroke, which are deliberated in this
      review.

PMID- 22645110
TI  - Is slack an intrinsic seizure terminator?
AB  - Understanding how epileptic seizures are initiated and propagated across large
      brain networks is difficult, but an even greater mystery is what makes them stop.
      Failure of spontaneous seizure termination leads to status epilepticus-a state of
      uninterrupted seizure activity that can cause death or permanent brain damage.
      Global factors, like changes in neuromodulators and ion concentrations, are
      likely to play major roles in spontaneous seizure cessation, but individual
      neurons also have intrinsic active ion currents that may contribute. The recently
      discovered gene Slack encodes a sodium-activated potassium channel that mediates
      a major proportion of the outward current in many neurons. Although given little
      attention, the current flowing through this channel may have properties
      consistent with a role in seizure termination.

PMID- 22645111
TI  - A novel look at astrocytes: aquaporins, ionic homeostasis, and the role of the
      microenvironment for regeneration in the CNS.
AB  - Aquaporin-4 (AQP4) water channels are located at the basolateral membrane domain
      of many epithelial cells involved in ion transport and secretion. These
      epithelial cells separate fluid compartments by forming apical tight junctions.
      In the brain, AQP4 is located on astrocytes in a polarized distribution: At the
      border to blood vessels or the pial surface, its density is very high. During
      ontogeny and phylogeny, astroglial cells go through a stage of expressing tight
      junctions, separating fluid compartments differently than in adult mammals. In
      adult mammals, this barrier is formed by arachnoid, choroid plexus, and
      endothelial cells. The ontogenetic and phylogenetic barrier transition from glial
      to endothelial cells correlates with the regenerative capacity of neuronal
      structures: Glial cells forming tight junctions, and expressing no or unpolarized
      AQP4 are found in the fish optic nerve and the olfactory nerve in mammals both
      known for their regenerative ability. It is hypothesized that highly polarized
      AQP4 expression and the lack of tight junctions on astrocytes increase ionic
      homeostasis, thus improving neuronal performance possibly at the expense of
      restraining neurogenesis and regeneration.

PMID- 22645112
TI  - Myotubular myopathy and the neuromuscular junction: a novel therapeutic approach
      from mouse models.
AB  - Myotubular myopathy (MTM) is a severe congenital muscle disease characterized by
      profound weakness, early respiratory failure and premature lethality. MTM is
      defined by muscle biopsy findings that include centralized nuclei and
      disorganization of perinuclear organelles. No treatments currently exist for MTM.
      We hypothesized that aberrant neuromuscular junction (NMJ) transmission is an
      important and potentially treatable aspect of the disease pathogenesis. We tested
      this hypothesis in two murine models of MTM. In both models we uncovered evidence
      of a disorder of NMJ transmission: fatigable weakness, improved strength with
      neostigmine, and electrodecrement with repetitive nerve stimulation.
      Histopathological analysis revealed abnormalities in the organization, appearance
      and size of individual NMJs, abnormalities that correlated with changes in
      acetylcholine receptor gene expression and subcellular localization. We
      additionally determined the ability of pyridostigmine, an acetylcholinesterase
      inhibitor, to ameliorate aspects of the behavioral phenotype related to NMJ
      dysfunction. Pyridostigmine treatment resulted in significant improvement in
      fatigable weakness and treadmill endurance. In all, these results describe a
      newly identified pathological abnormality in MTM, and uncover a potential disease
      modifying therapy for this devastating disorder.

PMID- 22645113
TI  - Expression pattern of apurinic/apyrimidinic endonuclease in sinonasal squamous
      cell carcinoma.
AB  - OBJECTIVE: To evaluate the apurinic/apyrimidinic endonuclease 1 (APE1) expression
      in sinonasal squamous cell carcinomas (SCC) and to examine the correlation
      between APE1 expression patterns and various clinicopathological factors
      associated with sinonasal SCC that include SCC with inverted papilloma (SCCwIP)
      and SCC alone. STUDY DESIGN: Case-control study. SETTING: Chungnam National
      University Hospital. SUBJECTS AND METHODS: The expressions of APE1 were analyzed
      by means of immunohistochemistry in 30 sinonasal SCC, including 14 SCC patients
      associated with IP and 16 patients with SCC alone. A total of 19 patients who had
      been diagnosed with chronic rhinosinusitis with nasal polyposis and who required
      endoscopic sinus surgery were used as the control group. The degrees of APE1
      expression were analyzed with respect to the following clinicopathologic
      variables: age, sex, T stage, histologic differentiation, distant metastasis, and
      recurrence. RESULTS: Cytoplasmic staining of APE1 was significantly higher in SCC
      compared with SCCwIP (68.75% vs 14.29%). Cytoplasmic staining of APE1 was
      significantly associated with T stage (P = .044) in SCC and histologic grade (P =
      .0025) in sinonasal SCC. Nuclear staining of APE1 was significantly associated
      with distant metastasis (P = .022) in SCC. CONCLUSION: These results suggest that
      the nuclear and cytoplasmic expression of APE1 may be related to tumor
      invasiveness and prognosis in sinonasal SCC. The suppression of APE1 expression
      can potentially be a new target for future sinonasal SCC therapies.

PMID- 22645114
TI  - Mitomycin C-enhanced revision endoscopic dacryocystorhinostomy: a prospective
      randomized controlled trial.
AB  - OBJECTIVES: (1) To conduct an adequately powered randomized controlled trial
      investigating the safety and efficacy of mitomycin C-enhanced revision endoscopic
      dacryocystorhinostomy (DCR) and (2) to analyze causes of failure after primary
      endoscopic DCR. STUDY DESIGN: A randomized controlled study. SETTING: General
      hospital. SUBJECTS AND METHODS: Seventy-six revision endoscopic DCRs were
      randomized into 2 groups: endoscopic DCR with mitomycin (group I), where 0.5
      mg/mL mitomycin C was applied for 10 minutes, and endoscopic DCR without
      mitomycin (group II). Follow-up settings were done to document the patient's
      subjective improvement, to judge ostium patency on irrigation, and to record any
      complications. RESULTS: Causes of failure in the original 92 patients included
      canalicular obstruction (14%), small misplaced bony window (43%), very small
      nasolacrimal stoma due to development of synechia (23%), and complete closure of
      nasolacrimal stoma with tough fibrous tissue (63%). There was no significant
      difference between the 2 groups in subjective and objective success rates and
      adverse events. Group I demonstrated a significantly longer operative time and a
      significantly lower number of debridement sessions (mean of 1.2 vs 1.9).
      CONCLUSIONS: Recurrent nasolacrimal duct obstruction after primary endoscopic DCR
      is mainly due to reclosure of the nasolacrimal stoma with synechia and fashioning
      of the small misplaced bony window. Mitomycin C does not increase the success
      rate of revision endoscopic DCR. It is a safe procedure and may be of value only
      in patients inaccessible to strict follow-up because it induces a better healing
      profile in terms of mucosal recovery, wound healing, and less need for
      debridement sessions.

PMID- 22645115
TI  - Endodermal cell-cell contact is required for the spatial control of Casparian
      band development in Arabidopsis thaliana.
AB  - BACKGROUND AND AIMS: Apoplasmic barriers in plants fulfil important roles such as
      the control of apoplasmic movement of substances and the protection against
      invasion of pathogens. The aim of this study was to describe the development of
      apoplasmic barriers (Casparian bands and suberin lamellae) in endodermal cells of
      Arabidopsis thaliana primary root and during lateral root initiation. METHODS:
      Modifications of the endodermal cell walls in roots of wild-type Landsberg erecta
      (Ler) and mutants with defective endodermal development - scarecrow-3 (scr-3) and
      shortroot (shr) - of A. thaliana plants were characterized by light, fluorescent,
      confocal laser scanning, transmission and cryo-scanning electron microscopy. KEY
      RESULTS: In wild-type plant roots Casparian bands initiate at approx. 1600 um
      from the root cap junction and suberin lamellae first appear on the inner primary
      cell walls at approx. 7000-8000 um from the root apex in the region of developing
      lateral root primordia. When a single cell replaces a pair of endodermal and
      cortical cells in the scr-3 mutant, Casparian band-like material is deposited
      ectopically at the junction between this 'cortical' cell and adjacent pericycle
      cells. Shr mutant roots with an undeveloped endodermis deposit Casparian band
      like material in patches in the middle lamellae of cells of the vascular
      cylinder. Endodermal cells in the vicinity of developing lateral root primordia
      develop suberin lamellae earlier, and these are thicker, compared wih the
      neighbouring endodermal cells. Protruding primordia are protected by an
      endodermal pocket covered by suberin lamellae. CONCLUSIONS: The data suggest that
      endodermal cell-cell contact is required for the spatial control of Casparian
      band development. Additionally, the endodermal cells form a collet (collar) of
      short cells covered by a thick suberin layer at the base of lateral root, which
      may serve as a barrier constituting a 'safety zone' protecting the vascular
      cylinder against uncontrolled movement of water, solutes or various pathogens.

PMID- 22645116
TI  - Early Zn2+-induced effects on membrane potential account for primary heavy metal
      susceptibility in tolerant and sensitive Arabidopsis species.
AB  - BACKGROUND AND AIMS: Uptake of heavy metals by plant root cells depends on
      electro-physiological parameters of the plasma membrane. In this study, responses
      of the plasma membrane in root cells were analysed where early reactions to the
      metal ion-induced stress are localized. Three different Arabidopsis species with
      diverse strategies of their adaptation to heavy metals were compared: sensitive
      Arabidopsis thaliana and tolerant A. halleri and A. arenosa. METHODS: Plants of
      A. thaliana Col-0 ecotype and plants of A. arenosa and A. halleri originating
      from natural metallicolous populations were exposed to high concentrations of
      Zn(2+). Plants were tested for root growth rate, cellular tolerance, plant
      morphology and cell death in the root apex. In addition, the membrane potential
      (E(M)) of mature cortical root cells and changes in the pH of the liquid culture
      media were measured. KEY RESULTS: Primary roots of A. halleri and A. arenosa
      plants grew significantly better at increased Zn(2+) concentrations than A.
      thaliana plants. Elevated Zn(2+) concentrations in the culture medium induced
      rapid changes in E(M). The reaction was species-specific and concentration
      dependent. Arabidopsis halleri revealed the highest insensitivity of the plasma
      membrane and the highest survival rate under prolonged treatment with extra-high
      concentrations. Plants were able to effectively adjust the pH in the control, but
      much less at Zn(2+)-induced lower pH. CONCLUSIONS: The results indicate a similar
      mode of early reaction to Zn(2+), but with different extent in tolerant and
      sensitive species of Arabidopsis. The sensitivity of A. thaliana and a high
      tolerance of A. halleri and A. arenosa were demonstrated. Plasma membrane
      depolarization was lowest in the hyperaccumulator A. halleri and highest in A.
      thaliana. This indicates that rapid membrane voltage changes are an excellent
      tool to monitor the effects of heavy metals.

PMID- 22645117
TI  - Will genomic selection be a practical method for plant breeding?
AB  - BACKGROUND: Genomic selection or genome-wide selection (GS) has been highlighted
      as a new approach for marker-assisted selection (MAS) in recent years. GS is a
      form of MAS that selects favourable individuals based on genomic estimated
      breeding values. Previous studies have suggested the utility of GS, especially
      for capturing small-effect quantitative trait loci, but GS has not become a
      popular methodology in the field of plant breeding, possibly because there is
      insufficient information available on GS for practical use. SCOPE: In this
      review, GS is discussed from a practical breeding viewpoint. Statistical
      approaches employed in GS are briefly described, before the recent progress in GS
      studies is surveyed. GS practices in plant breeding are then reviewed before
      future prospects are discussed. CONCLUSIONS: Statistical concepts used in GS are
      discussed with genetic models and variance decomposition, heritability, breeding
      value and linear model. Recent progress in GS studies is reviewed with a focus on
      empirical studies. For the practice of GS in plant breeding, several specific
      points are discussed including linkage disequilibrium, feature of populations and
      genotyped markers and breeding scheme. Currently, GS is not perfect, but it is a
      potent, attractive and valuable approach for plant breeding. This method will be
      integrated into many practical breeding programmes in the near future with
      further advances and the maturing of its theory.

PMID- 22645118
TI  - Estimation of heritability, evolvability and genetic correlations of two pollen
      and pistil traits involved in a sexual conflict over timing of stigma receptivity
      in Collinsia heterophylla (Plantaginaceae).
AB  - BACKGROUND AND AIMS: Heritable genetic variation is crucial for selection to
      operate, yet there is a paucity of studies quantifying such variation in
      interactive male/female sexual traits, especially those of plants. Previous work
      on the annual plant Collinsia heterophylla, a mixed-mating species, suggests that
      delayed stigma receptivity is involved in a sexual conflict: pollen from certain
      donors fertilize ovules earlier than others at the expense of reduced maternal
      seed set and lower levels of pollen competition. METHODS: Parent-offspring
      regressions and sib analyses were performed to test for heritable genetic
      variation and co-variation in male and female interactive traits related to the
      sexual conflict. KEY RESULTS: SOME heritable variation and evolvability were
      found for the female trait (delayed stigma receptivity in presence of pollen),
      but no evidence was found for genetic variation in the male trait (ability to
      fertilize ovules early). The results further indicated a marginally significant
      correlation between a male's ability to fertilize early and early stigma
      receptivity in offspring. However, despite potential indirect selection of these
      traits, antagonistic co-evolution may not occur given the lack of heritability of
      the male trait. CONCLUSIONS: To our knowledge, this is the first study of a plant
      or any hermaphrodite that examines patterns of genetic correlation between two
      interactive sexual traits, and also the first to assess heritabilities of plant
      traits putatively involved in a sexual conflict. It is concluded that the ability
      to delay fertilization in presence of pollen can respond to selection, while the
      pollen trait has lower evolutionary potential.

PMID- 22645119
TI  - Hospital readmissions for catheter-related bloodstream infection and use of
      ethanol lock therapy: comparison of patients receiving parenteral nutrition or
      intravenous fluids in the home vs a skilled nursing facility.
AB  - BACKGROUND: Catheter-related bloodstream infection (CRBSI) is the most serious
      long-term infectious complication of long-term home parenteral nutrition (PN).
      Ethanol is being used more commonly as a catheter locking solution in the home PN
      setting for prevention of CRBSI; however, no current literature reports the use
      of ethanol lock (ETL) in skilled nursing facility (SNF) patients. METHODS: The
      authors evaluated the number of hospital readmissions for CRBSI and length of
      stay between SNF (not receiving ETL) and home patients (receiving or not
      receiving ETL) receiving PN or intravenous fluid therapy. RESULTS: SNF patients
      had a significantly longer length of stay (LOS) for CRBSI hospital admissions
      compared with patients receiving PN at home with or without ETL (P < .001; 16 vs
      8 vs 8 days). There was no LOS difference for CRBSI between home patients with or
      without ETL. Home PN patients not receiving ETL were more likely to have a CRBSI
      from Staphylococcus sp (48% vs 27%; P = .015), whereas SNF PN patients not
      receiving ETL were more likely to have a CRBSI from Enterococcus sp (16% vs 3%; P
      = .004). CONCLUSION: Despite different causative organisms and medical acuity
      likely affecting the differences observed in LOS, the SNF population is another
      setting ETL can be used to prevent CRBSI.

PMID- 22645120
TI  - Resting energy expenditure after fontan surgery in children with single-ventricle
      heart defects.

PMID- 22645121
TI  - Jonathan E. Rhoads lecture 2012: improving patient care with practice-based
      research.
AB  - Practice-based research plays a pivotal role for improving patient care as its
      primary intent is to solve a clinical dilemma or problem encountered in clinical
      practice. Its results are immediately applicable to day-to-day clinical practice
      and essential to the growth of an evidence-based clinical practice. This review
      emphasizes the importance of this type of research. In addition, it serves to
      identify common sources for project conception and gives examples based on
      personal experiences of the author as a clinical practitioner, educator, and
      researcher. Common barriers to practice-based research are discussed as well as
      potential solutions offered for consideration.

PMID- 22645122
TI  - Transcriptome analysis of a North American songbird, Melospiza melodia.
AB  - An effective way to understand the genomics of divergence in non-model organisms
      is to use the transcriptome to identify genes associated with divergence. We
      examine the transcriptome of the song sparrow (Melospiza melodia) and contrast it
      with the avian models zebra finch (Taeniopygia guttata) and chicken (Gallus
      gallus). We aimed to (i) obtain a functional annotation of a substantial portion
      of the song sparrow transcriptome; (ii) compare transcript divergence; (iii)
      efficiently characterize single nucleotide polymorphism/indel markers possibly
      fixed between song sparrow subspecies; and (iv) identify the most common set of
      transcripts in birds using the zebra finch as a reference. Using two individuals
      from each of three populations, whole-body mRNA was normalized and sequenced (110
      Mb total). The assembly yielded 38,539 contigs [N50 (the length-weighted median)
      = 482 bp]; 4574 were orthologous to both model genomes and 3680 are functionally
      annotated. This low-coverage scan of the song sparrow transcriptome revealed
      29,982 SNPs/indels, 1402 fixed between populations and subspecies. Referencing
      zebra finch and chicken, we identified 43 and 5 fast-evolving genes,
      respectively. We also identified the most common set of transcripts present in
      birds with respect to zebra finch. This study provides new insight into songbird
      transcriptomes, and candidate markers identified here may help research in
      songbirds (oscine Passeriformes), a frequently studied group.

PMID- 22645124
TI  - Ultrahigh and high resolution structures and mutational analysis of monomeric
      Streptococcus pyogenes SpeB reveal a functional role for the glycine-rich C
      terminal loop.
AB  - Cysteine protease SpeB is secreted from Streptococcus pyogenes and has been
      studied as a potential virulence factor since its identification almost 70 years
      ago. Here, we report the crystal structures of apo mature SpeB to 1.06 A
      resolution as well as complexes with the general cysteine protease inhibitor
      trans-epoxysuccinyl-l-leucylamido(4-guanidino)butane and a novel substrate
      mimetic peptide inhibitor. These structures uncover conformational changes
      associated with maturation of SpeB from the inactive zymogen to its active form
      and identify the residues required for substrate binding. With the use of a newly
      developed fluorogenic tripeptide substrate to measure SpeB activity, we
      determined IC(50) values for trans-epoxysuccinyl-l-leucylamido(4-guanidino)butane
      and our new peptide inhibitor and the effects of mutations within the C-terminal
      active site loop. The structures and mutational analysis suggest that the
      conformational movements of the glycine-rich C-terminal loop are important for
      the recognition and recruitment of biological substrates and release of
      hydrolyzed products.

PMID- 22645123
TI  - Down-regulation of NF-kappaB transcriptional activity in HIV-associated kidney
      disease by BRD4 inhibition.
AB  - NF-kappaB-mediated inflammation is the major pathology in chronic kidney
      diseases, including HIV-associated nephropathy (HIVAN) that ultimately progresses
      to end stage renal disease. HIV infection in the kidney induces NF-kappaB
      activation, leading to the production of proinflammatory chemokines, cytokines,
      and adhesion molecules. In this study, we explored selective inhibition of NF
      kappaB transcriptional activity by small molecule blocking NF-kappaB binding to
      the transcriptional cofactor BRD4, which is required for the assembly of the
      productive transcriptional complex comprising positive transcription elongation
      factor b and RNA polymerase II. We showed that our BET (Bromodomain and Extra
      Terminal domain)-specific bromodomain inhibitor MS417, designed to block BRD4
      binding to the acetylated NF-kappaB, effectively attenuates NF-kappaB
      transcriptional activation of proinflammatory genes in kidney cells treated with
      TNFalpha or infected by HIV. MS417 ameliorates inflammation and kidney injury in
      HIV-1 transgenic mice, an animal model for HIVAN. Our study suggests that BET
      bromodomain inhibition, targeting at the proinflammatory activity of NF-kappaB,
      represents a new therapeutic approach for treating NF-kappaB-mediated
      inflammation and kidney injury in HIVAN.

PMID- 22645125
TI  - Synthetic human monoclonal antibodies toward staphylococcal enterotoxin B (SEB)
      protective against toxic shock syndrome.
AB  - Staphylococcal enterotoxin B (SEB) is a potent toxin that can cause toxic shock
      syndrome and act as a lethal and incapacitating agent when used as a bioweapon.
      There are currently no vaccines or immunotherapeutics available against this
      toxin. Using phage display technology, human antigen-binding fragments (Fabs)
      were selected against SEB, and proteins were produced in Escherichia coli cells
      and characterized for their binding affinity and their toxin neutralizing
      activity in vitro and in vivo. Highly protective Fabs were converted into full
      length IgGs and produced in mammalian cells. Additionally, the production of anti
      SEB antibodies was explored in the Nicotiana benthamiana plant expression system.
      Affinity maturation was performed to produce optimized lead anti-SEB antibody
      candidates with subnanomolar affinities. IgGs produced in N. benthamiana showed
      characteristics comparable with those of counterparts produced in mammalian
      cells. IgGs were tested for their therapeutic efficacy in the mouse toxic shock
      model using different challenge doses of SEB and a treatment with 200 MUg of IgGs
      1 h after SEB challenge. The lead candidates displayed full protection from
      lethal challenge over a wide range of SEB challenge doses. Furthermore, mice that
      were treated with anti-SEB IgG had significantly lower IFNgamma and IL-2 levels
      in serum compared with mock-treated mice. In summary, these anti-SEB monoclonal
      antibodies represent excellent therapeutic candidates for further preclinical and
      clinical development.

PMID- 22645126
TI  - Reactive oxygen species-mediated immunity against Leishmania mexicana and
      Serratia marcescens in the sand phlebotomine fly Lutzomyia longipalpis.
AB  - Phlebotomine sand flies are the vectors of medically important Leishmania. The
      Leishmania protozoa reside in the sand fly gut, but the nature of the immune
      response to the presence of Leishmania is unknown. Reactive oxygen species (ROS)
      are a major component of insect innate immune pathways regulating gut-microbe
      homeostasis. Here we show that the concentration of ROS increased in sand fly
      midguts after they fed on the insect pathogen Serratia marcescens but not after
      feeding on the Leishmania that uses the sand fly as a vector. Moreover, the
      Leishmania is sensitive to ROS either by oral administration of ROS to the
      infected fly or by silencing a gene that expresses a sand fly ROS-scavenging
      enzyme. Finally, the treatment of sand flies with an exogenous ROS scavenger
      (uric acid) altered the gut microbial homeostasis, led to an increased commensal
      gut microbiota, and reduced insect survival after oral infection with S.
      marcescens. Our study demonstrates a differential response of the sand fly ROS
      system to gut microbiota, an insect pathogen, and the Leishmania that utilize the
      sand fly as a vehicle for transmission between mammalian hosts.

PMID- 22645127
TI  - Myb-binding protein 1a (Mybbp1a) regulates levels and processing of pre-ribosomal
      RNA.
AB  - Ribosomal RNA gene transcription, co-transcriptional processing, and ribosome
      biogenesis are highly coordinated processes that are tightly regulated during
      cell growth. In this study we discovered that Mybbp1a is associated with both the
      RNA polymerase I complex and the ribosome biogenesis machinery. Using a reporter
      assay that uncouples transcription and RNA processing, we show that Mybbp1a
      represses rRNA gene transcription. In addition, overexpression of the protein
      reduces RNA polymerase I loading on endogenous rRNA genes as revealed by
      chromatin immunoprecipitation experiments. Accordingly, depletion of Mybbp1a
      results in an accumulation of the rRNA precursor in vivo but surprisingly also
      causes growth arrest of the cells. This effect can be explained by the
      observation that the modulation of Mybbp1a protein levels results in defects in
      pre-rRNA processing within the cell. Therefore, the protein may play a dual role
      in the rRNA metabolism, potentially linking and coordinating ribosomal DNA
      transcription and pre-rRNA processing to allow for the efficient synthesis of
      ribosomes.

PMID- 22645128
TI  - Partial enzymatic deglycosylation preserves the structure of cleaved recombinant
      HIV-1 envelope glycoprotein trimers.
AB  - The trimeric envelope glycoprotein complex (Env) is the focus of vaccine
      development programs aimed at generating protective humoral responses to human
      immunodeficiency virus type 1 (HIV-1). N-Linked glycans, which constitute almost
      half of the molecular mass of the external Env domains, produce considerable
      structural heterogeneity and are a major impediment to crystallization studies.
      Moreover, by shielding the peptide backbone, glycans can block attempts to
      generate neutralizing antibodies against a substantial subset of potential
      epitopes when Env proteins are used as immunogens. Here, we describe the partial
      deglycosylation of soluble, cleaved recombinant Env trimers by inhibition of the
      synthesis of complex N-glycans during Env production, followed by treatment with
      glycosidases under conditions that preserve Env trimer integrity. The partially
      deglycosylated trimers are stable, and neither abnormally sensitive to
      proteolytic digestion nor prone to aggregation. Moreover, the deglycosylated
      trimers retain or increase their ability to bind CD4 and antibodies that are
      directed to conformational epitopes, including the CD4-binding site and the V3
      region. However, as expected, they do not react with glycan-dependent antibodies
      2G12 and PGT123, or the C-type lectin receptor DC-SIGN. Electron microscopic
      analysis shows that partially deglycosylated trimers have a structure similar to
      fully glycosylated trimers, indicating that removal of glycans does not
      substantially perturb the structural integrity of the trimer. The glycan-depleted
      Env trimers should be useful for structural and immunogenicity studies.

PMID- 22645129
TI  - Lewis X-carrying N-glycans regulate the proliferation of mouse embryonic neural
      stem cells via the Notch signaling pathway.
AB  - Neural stem cells (NSCs) possess high proliferative potential and the capacity
      for self-renewal with retention of multipotency to differentiate into brain
      forming cells. Several signaling pathways have been shown to be involved in the
      fate determination process of NSCs, but the molecular mechanisms underlying the
      maintenance of neural cell stemness remain largely unknown. Our previous study
      showed that human natural killer carbohydrate epitopes expressed specifically by
      mouse NSCs modulate the Ras-MAPK pathway, raising the possibility of regulatory
      roles of glycoprotein glycans in the specific signaling pathways involved in NSC
      fate determination. To address this issue, we performed comparative N
      glycosylation profiling of NSCs before and after differentiation in a
      comprehensive and quantitative manner. We found that Lewis X-carrying N-glycans
      were specifically displayed on undifferentiated cells, whereas pauci-mannose-type
      N-glycans were predominantly expressed on differentiated cells. Furthermore, by
      knocking down a fucosyltransferase 9 with short interfering RNA, we demonstrated
      that the Lewis X-carrying N-glycans were actively involved in the proliferation
      of NSCs via modulation of the expression level of Musashi-1, which is an
      activator of the Notch signaling pathway. Our findings suggest that Lewis X
      carbohydrates, which have so far been characterized as undifferentiation markers,
      actually operate as activators of the Notch signaling pathway for the maintenance
      of NSC stemness during brain development.

PMID- 22645130
TI  - GPR30 regulates glutamate transporter GLT-1 expression in rat primary astrocytes.
AB  - The G protein-coupled estrogen receptor GPR30 contributes to the neuroprotective
      effects of 17beta-estradiol (E2); however, the mechanisms associated with this
      protection have yet to be elucidated. Given that E2 increases astrocytic
      expression of glutamate transporter-1 (GLT-1), which would prevent excitotoxic
      induced neuronal death, we proposed that GPR30 mediates E2 action on GLT-1
      expression. To investigate this hypothesis, we examined the effects of G1, a
      selective agonist of GPR30, and GPR30 siRNA on astrocytic GLT-1 expression, as
      well as glutamate uptake in rat primary astrocytes, and explored potential
      signaling pathways linking GPR30 to GLT-1. G1 increased GLT-1 protein and mRNA
      levels, subject to regulation by both MAPK and PI3K signaling. Inhibition of TGF
      alpha receptor suppressed the G1-induced increase in GLT-1 expression. Silencing
      GPR30 reduced the expression of both GLT-1 and TGF-alpha and abrogated the G1
      induced increase in GLT-1 expression. Moreover, the G1-induced increase in GLT-1
      protein expression was abolished by a protein kinase A inhibitor and an NF-kappaB
      inhibitor. G1 also enhanced cAMP response element-binding protein (CREB), as well
      as both NF-kappaB p50 and NF-kappaB p65 binding to the GLT-1 promoter. Finally,
      to model dysfunction of glutamate transporters, manganese was used, and G1 was
      found to attenuate manganese-induced impairment in GLT-1 protein expression and
      glutamate uptake. Taken together, the present data demonstrate that activation of
      GPR30 increases GLT-1 expression via multiple pathways, suggesting that GPR30 is
      worthwhile as a potential target to be explored for developing therapeutics of
      excitotoxic neuronal injury.

PMID- 22645131
TI  - Signaling active CD95 receptor molecules trigger co-translocation of inactive
      CD95 molecules into lipid rafts.
AB  - The capability of soluble CD95L trimers to trigger CD95-associated signaling
      pathways is drastically increased by oligomerization. The latter can be achieved,
      for example, by antibodies recognizing a N-terminal epitope tag in recombinant
      CD95L variants or by genetic engineering-enforced formation of hexamers. Using
      highly sensitive and accurate binding studies with recombinant CD95L variants
      equipped with a Gaussia princeps luciferase reporter domain, we found that
      oligomerization of CD95L has no major effect on CD95 occupancy. This indicates
      that the higher activity of oligomerized CD95L trimers is not related to an
      avidity-related increase in apparent affinity and points instead to a crucial
      role of aggregation of initially formed trimeric CD95L-CD95 complexes in CD95
      activation. Furthermore, binding of soluble CD95L trimers was found to be
      insufficient to increase the association of CD95 with the lipid raft-containing
      membrane fraction. However, when Gaussia princeps luciferase-CD95L trimers were
      used as tracers to "mark" inactive CD95 molecules, increased association of these
      inactive receptors was observed upon activation of the remaining CD95 molecules
      by help of highly active hexameric Fc-CD95L or membrane CD95L. Moreover, in cells
      expressing endogenous CD95 and chimeric CD40-CD95 receptors, triggering of CD95
      signaling via endogenous CD95 resulted in co-translocation of CD40-CD95 to the
      lipid raft fraction, whereas vice versa activation of CD95-associated pathways
      with Fc-CD40L via CD40-CD95 resulted in co-translocation of endogenous CD95. In
      sum, this shows that signaling-active CD95 molecules not only enhance their own
      association with the lipid raft-containing membrane fraction but also those of
      inactive CD95 molecules.

PMID- 22645132
TI  - Monomer-monomer interactions propagate structural transitions necessary for pore
      formation by the cholesterol-dependent cytolysins.
AB  - The assembly of the cholesterol-dependent cytolysin (CDC) oligomeric pore complex
      requires a complex choreography of secondary and tertiary structural changes in
      domain 3 (D3) of the CDC monomer structure. A point mutation was identified in
      the archetype CDC, perfringolysin O, that blocks detectable D3 structural changes
      and traps the membrane-bound monomers in an early and reversible stage of
      oligomer assembly. Using this and other mutants we show that specific D3
      structural changes are propagated from one membrane-bound monomer to another.
      Propagation of these structural changes results in the exposure of a beta-strand
      in D3 that allows it to pair and form edge-on interactions with a second beta
      strand of a free membrane-bound monomer. Pairing of these strands establishes the
      final geometry of the pore complex and is necessary to drive the formation of the
      beta-barrel pore. These studies provide new insights into how structural
      information is propagated between membrane-bound monomers of a self-assembling
      system and the interactions that establish the geometry of the final pore
      complex.

PMID- 22645133
TI  - Mechanistic insights into regulated cargo binding by ACAP1 protein.
AB  - Coat complexes sort protein cargoes into vesicular transport pathways. An
      emerging class of coat components has been the GTPase-activating proteins (GAPs)
      that act on the ADP-ribosylation factor (ARF) family of small GTPases. ACAP1
      (ArfGAP with coiled-coil, ankyrin repeat, and PH domains protein 1) is an ARF6
      GAP that also acts as a key component of a recently defined clathrin complex for
      endocytic recycling. Phosphorylation by Akt has been shown to enhance cargo
      binding by ACAP1 in explaining how integrin recycling is an example of regulated
      transport. We now shed further mechanistic insights into how this regulation is
      achieved at the level of cargo binding by ACAP1. We initially defined a critical
      sequence in the cytoplasmic domain of integrin beta1 recognized by ACAP1 and
      showed that this sequence acts as a recycling sorting signal. We then pursued a
      combination of structural, modeling, and functional studies, which suggest that
      phosphorylation of ACAP1 relieves a localized mechanism of autoinhibition in
      regulating cargo binding. Thus, we have elucidated a key regulatory juncture that
      controls integrin recycling and also advanced the understanding of how regulated
      cargo binding can lead to regulated transport.

PMID- 22645135
TI  - Structural basis for activation of an integral membrane protease by
      lipopolysaccharide.
AB  - Omptins constitute a unique family of outer membrane proteases that are
      widespread in Enterobacteriaceae. The plasminogen activator (Pla) of Yersinia
      pestis is an omptin family member that is very important for development of both
      bubonic and pneumonic plague. The physiological function of Pla is to cleave
      (activate) human plasminogen to form the plasma protease plasmin. Uniquely,
      lipopolysaccharide (LPS) is essential for the catalytic activity of all omptins,
      including Pla. Why omptins require LPS for enzymatic activity is unknown. Here,
      we report the co-crystal structure of LPS-free Pla in complex with the activation
      loop peptide of human plasminogen, its natural substrate. The structure shows
      that in the absence of LPS, the peptide substrate binds deep within the active
      site groove and displaces the nucleophilic water molecule, providing an
      explanation for the dependence of omptins on LPS for enzymatic activity.

PMID- 22645134
TI  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein-induced
      lysosomal translocation of proapoptotic effectors is mediated by phosphofurin
      acidic cluster sorting protein-2 (PACS-2).
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis
      of liver cancer cell lines requires death receptor-5 (DR5)-dependent
      permeabilization of lysosomal membranes. Ligated DR5 triggers recruitment of the
      proapoptotic proteins Bim and Bax to lysosomes, releasing cathepsin B into the
      cytosol where it mediates mitochondria membrane permeabilization and activation
      of executioner caspases. Despite the requirement for lysosome membrane
      permeabilization during TRAIL-induced apoptosis, little is known about the
      mechanism that controls recruitment of Bim and Bax to lysosomal membranes. Here
      we report that TRAIL induces recruitment of the multifunctional sorting protein
      phosphofurin acidic cluster sorting protein-2 (PACS-2) to DR5-positive endosomes
      in Huh-7 cells where it forms an immunoprecipitatable complex with Bim and Bax on
      lysosomal membranes. shRNA-targeted knockdown of PACS-2 prevents recruitment of
      Bim or Bax to lysosomes, blunting the TRAIL-induced lysosome membrane
      permeabilization. Consistent with the reduced lysosome membrane permeabilization,
      shRNA knockdown of PACS-2 in Huh-7 cells reduced TRAIL-induced apoptosis and
      increased clonogenic cell survival. The determination that recombinant PACS-2
      bound Bim but not Bax in vitro and that shRNA knockdown of Bim blocked Bax
      recruitment to lysosomes suggests that TRAIL/DR5 triggers endosomal PACS-2 to
      recruit Bim and Bax to lysosomes to release cathepsin B and induce apoptosis.
      Together, these findings provide insight into the lysosomal pathway of apoptosis.

PMID- 22645136
TI  - A variant of the breast cancer type 2 susceptibility protein (BRC) repeat is
      essential for the RECQL5 helicase to interact with RAD51 recombinase for genome
      stabilization.
AB  - The BRC repeat is a structural motif in the tumor suppressor BRCA2 (breast cancer
      type 2 susceptibility protein), which promotes homologous recombination (HR) by
      regulating RAD51 recombinase activity. To date, the BRC repeat has not been
      observed in other proteins, so that its role in HR is inferred only in the
      context of BRCA2. Here, we identified a BRC repeat variant, named BRCv, in the
      RECQL5 helicase, which possesses anti-recombinase activity in vitro and
      suppresses HR and promotes cellular resistance to camptothecin-induced
      replication stress in vivo. RECQL5-BRCv interacted with RAD51 through two
      conserved motifs similar to those in the BRCA2-BRC repeat. Mutations of either
      motif compromised functions of RECQL5, including association with RAD51,
      inhibition of RAD51-mediated D-loop formation, suppression of sister chromatid
      exchange, and resistance to camptothecin-induced replication stress. Potential
      BRCvs were also found in other HR regulatory proteins, including Srs2 and Sgs1,
      which possess anti-recombinase activities similar to that of RECQL5. A point
      mutation in the predicted Srs2-BRCv disrupted the ability of the protein to bind
      RAD51 and to inhibit D-loop formation. Thus, BRC is a common RAD51 interaction
      module that can be utilized by different proteins to either promote HR, as in the
      case of BRCA2, or to suppress HR, as in RECQL5.

PMID- 22645137
TI  - Regulation of class I major histocompatibility complex (MHC) by nucleotide
      binding domain, leucine-rich repeat-containing (NLR) proteins.
AB  - Most of the nucleotide-binding domain, leucine-rich repeat (NLR) proteins
      regulate responses to microbial and damage-associated products. Class II
      transactivator (CIITA) has a distinct function as the master regulator of class
      II major histocompatibility complex (MHC-II) transcription. Recently, human NLRC5
      was found to regulate MHC-I in cell lines; however, a host of conflicting
      positive and negative functions has been attributed to this protein. To address
      the function of NLRC5 in a physiologic setting, we generated an Nlrc5(-/-) strain
      that contains a deletion in the exon that encodes the nucleotide-binding domain.
      We have not detected a role for this protein in cytokine induction by pathogen
      associated molecular patterns and viruses. However, Nlrc5(-/-) cells showed a
      dramatic decrease of classical (H-2K) and nonclassical (Tla) MHC-I expression by
      T/B lymphocytes, natural killer (NK) cells, and myeloid-monocytic lineages. As a
      comparison, CIITA did not affect mouse MHC-I expression. Nlrc5(-/-) splenocytes
      and bone marrow-derived macrophages were able to up-regulate MHC-I in response to
      IFN-gamma; however, the absolute levels of MHC-I expression were significantly
      lower than WT controls. Chromatin immunoprecipitation of IFN-gamma-treated cells
      indicates that Nlrc5 reduced the silencing H3K27me3 histone modification, but did
      not affect the activating AcH3 modification on a MHC-I promoter. In summary, we
      conclude that Nlrc5 is important in the regulation of MHC-I expression by
      reducing H3K27me3 on MHC-I promoter and joins CIITA as an NLR subfamily that
      controls MHC gene transcription.

PMID- 22645138
TI  - Solution structure of the phosphotyrosine binding (PTB) domain of human tensin2
      protein in complex with deleted in liver cancer 1 (DLC1) peptide reveals a novel
      peptide binding mode.
AB  - The protein deleted in liver cancer 1 (DLC1) interacts with the tensin family of
      focal adhesion proteins to play a role as a tumor suppressor in a wide spectrum
      of human cancers. This interaction has been proven to be crucial to the oncogenic
      inhibitory capacity and focal adhesion localization of DLC1. The phosphotyrosine
      binding (PTB) domain of tensin2 predominantly interacts with a novel site on
      DLC1, not the canonical NPXY motif. In this study, we characterized this
      interaction biochemically and determined the complex structure of tensin2 PTB
      domain with DLC1 peptide by NMR spectroscopy. Our HADDOCK-derived complex
      structure model elucidates the molecular mechanism by which tensin2 PTB domain
      recognizes DLC1 peptide and reveals a PTB-peptide binding mode that is unique in
      that peptide occupies the binding site opposite to the canonical NPXY motif
      interaction site with the peptide utilizing a non-canonical binding motif to bind
      in an extended conformation and that the N-terminal helix, which is unique to
      some Shc- and Dab-like PTB domains, is required for binding. Mutations of crucial
      residues defined for the PTB-DLC1 interaction affected the co-localization of
      DLC1 and tensin2 in cells and abolished DLC1-mediated growth suppression of
      hepatocellular carcinoma cells. This tensin2 PTB-DLC1 peptide complex with a
      novel binding mode extends the versatile binding repertoire of the PTB domains in
      mediating diverse cellular signaling pathways as well as provides a molecular and
      structural basis for better understanding the tumor-suppressive activity of DLC1
      and tensin2.

PMID- 22645139
TI  - Exploring the topology of the Gid complex, the E3 ubiquitin ligase involved in
      catabolite-induced degradation of gluconeogenic enzymes.
AB  - In the yeast Saccharomyces cerevisiae, key regulatory enzymes of gluconeogenesis
      such as fructose-1,6-bisphosphatase are degraded via the ubiquitin proteasome
      system when cells are replenished with glucose. Polyubiquitination is carried out
      by the Gid complex, a multisubunit ubiquitin ligase that consists of seven
      different Gid (glucose-induced degradation-deficient) proteins. Under
      gluconeogenic conditions the E3 ligase is composed of six subunits (Gid1/Vid30,
      Gid2/Rmd5, Gid5/Vid28, Gid7, Gid8, and Gid9/Fyv10). Upon the addition of glucose
      the regulatory subunit Gid4/Vid24 appears, binds to the Gid complex, and triggers
      ubiquitination of fructose-1,6-bisphosphatase. All seven proteins are essential
      for this process; however, nothing is known about the arrangement of the subunits
      in the complex. Interestingly, each Gid protein possesses several remarkable
      motifs (e.g. SPRY, LisH, CTLH domains) that may play a role in protein-protein
      interaction. We, therefore, generated altered versions of individual Gid proteins
      by deleting or mutating these domains and performed co-immunoprecipitation
      experiments to analyze the interaction between distinct subunits. Thus, we were
      able to create an initial model of the topology of this unusual E3 ubiquitin
      ligase.

PMID- 22645141
TI  - Short term high fat diet challenge promotes alternative macrophage polarization
      in adipose tissue via natural killer T cells and interleukin-4.
AB  - Inflammation in adipose tissue plays an important role in the pathogenesis of
      obesity-associated complications. However, the detailed cellular events
      underlying the inflammatory changes at the onset of obesity have not been
      characterized. Here we show that an acute HFD challenge is unexpectedly
      associated with elevated alternative (M2) macrophage polarization in adipose
      tissue mediated by Natural Killer T (NKT) cells. Upon 4d HFD feeding, NKT cells
      are activated, promote M2 macrophage polarization and induce arginase 1
      expression via interleukin (IL)-4 in adipose tissue, not in the liver. In NKT
      deficient CD1d(-/-) mice, M2 macrophage polarization in adipose tissue is reduced
      while systemic glucose homeostasis and insulin tolerance are impaired upon 4d HFD
      challenge. Thus, our study demonstrate, for the first time to our knowledge, that
      acute HFD feeding is associated with remarkably pronounced and dynamic immune
      responses in adipose tissue, and adipose-resident NKT cells may link acute HFD
      feeding with inflammation.

PMID- 22645140
TI  - The role of glycine residues 140 and 141 of subunit B in the functional
      ubiquinone binding site of the Na+-pumping NADH:quinone oxidoreductase from
      Vibrio cholerae.
AB  - The Na(+)-pumping NADH:quinone oxidoreductase (Na(+)-NQR) is the main entrance
      for electrons into the respiratory chain of many marine and pathogenic bacteria.
      The enzyme accepts electrons from NADH and donates them to ubiquinone, and the
      free energy released by this redox reaction is used to create an electrochemical
      gradient of sodium across the cell membrane. Here we report the role of glycine
      140 and glycine 141 of the NqrB subunit in the functional binding of ubiquinone.
      Mutations at these residues altered the affinity of the enzyme for ubiquinol.
      Moreover, mutations in residue NqrB-G140 almost completely abolished the electron
      transfer to ubiquinone. Thus, NqrB-G140 and -G141 are critical for the binding
      and reaction of Na(+)-NQR with its electron acceptor, ubiquinone.

PMID- 22645142
TI  - Variants of Toll-like receptor 4 predict cardiac recovery in patients with
      dilated cardiomyopathy.
AB  - The clinical course of patients with dilated cardiomyopathy (DCM) varies from
      cardiac recovery to end stage heart failure. The etiology of this variability is
      largely unknown. In this study, we investigated the impact of coding
      polymorphisms of the innate immune protein Toll-like receptor 4 (TLR4) on left
      ventricular performance in patients with DCM. Two variants of TLR4 (rs4986790,
      TLR4 c.1187A->G, p.299D->G and rs4986791,TLR4 c.1487C->T, p.T399I) were
      investigated in 158 patients with DCM. Other reasons for heart failure were
      excluded by coronary angiography, myocardial biopsy, and echocardiography. Risk
      factors, age, gender, or treatment did not differ among the groups. At the follow
      up evaluation (median 4.0-5.4 months), patients carrying the TLR4 wild type gene
      displayed cardiac recovery under intense medical heart failure therapy indexed by
      reduced left ventricular dilation, improved left ventricular ejection fraction,
      and reduced NT-probrain natriuretic peptide blood level when compared with the
      initial evaluation. In contrast, patients carrying both the rs4986790 and the
      rs4986791 variant showed significantly reduced improvement of left ventricular
      ejection fraction (p = 0.006) and left ventricular dilation (p = 0.015) at the
      follow-up evaluation when compared with carriers of the wild type gene under the
      same treatment conditions. In addition, NT-probrain natriuretic peptide level in
      carriers of both TLR4 variants did not change significantly at the follow up when
      compared with the first evaluation. Among patients with DCM, the presence of the
      TLR4 variants rs4986790 and rs4986791 predicts impaired cardiac recovery
      independently of medical treatment or cardiac risk factors.

PMID- 22645143
TI  - Leukemia inhibitory factor coordinates the down-regulation of the visual cycle in
      the retina and retinal-pigmented epithelium.
AB  - Leukemia inhibitory factor (LIF), an interleukin-6 family neurocytokine, is up
      regulated in response to different types of retinal stress and has
      neuroprotective activity through activation of the gp130 receptor/STAT3 pathway.
      We observed that LIF induces rapid, robust, and sustained activation of STAT3 in
      both the retina and retinal pigmented epithelium (RPE). Here, we tested whether
      LIF-induced STAT3 activation within the RPE can down-regulate RPE65, the central
      enzyme in the visual cycle that provides the 11-cis-retinal chromophore to
      photoreceptors in vivo. We generated conditional knock-out mice to specifically
      delete STAT3 or gp130 in RPE, retina, or both RPE and retina. After intravitreal
      injection of LIF, we analyzed the expression levels of visual cycle genes and
      proteins, isomerase activity of RPE65, levels of rhodopsin protein, and the rates
      of dark adaptation and rhodopsin regeneration. We found that RPE65 protein levels
      and isomerase activity were reduced and recovery of bleachable rhodopsin was
      delayed in LIF-injected eyes. In mice with functional gp130/STAT3 signaling in
      the retina, rhodopsin protein was also reduced by LIF. However, the LIF-induced
      down-regulation of RPE65 required a functional gp130/STAT3 cascade intrinsic to
      RPE. Our data demonstrate that a single cytokine, LIF, can simultaneously and
      independently affect both RPE and photoreceptors through the same signaling
      cascade to reduce the generation and utilization of 11-cis-retinal.

PMID- 22645144
TI  - Leucine stimulates insulin secretion via down-regulation of surface expression of
      adrenergic alpha2A receptor through the mTOR (mammalian target of rapamycin)
      pathway: implication in new-onset diabetes in renal transplantation.
AB  - The amino acid leucine is a potent secretagogue, capable of inducing insulin
      secretion. It also plays an important role in the regulation of mTOR activity,
      therefore, providing impetus to investigate if a leucine-sensing mechanism in the
      mTOR pathway is involved in insulin secretion. We found that leucine-induced
      insulin secretion was inhibited by both the mTOR inhibitor rapamycin as well as
      the adrenergic alpha2 receptor agonist clonidine. We also demonstrated that
      leucine down-regulated the surface expression of adrenergic alpha2A receptor via
      activation of the mTOR pathway. The leucine stimulatory effect on insulin
      secretion was attenuated in diabetic Goto-Kakizaki rats that overexpress
      adrenergic alpha2A receptors, confirming the role of leucine in insulin
      secretion. Thus, our data demonstrate that leucine regulates insulin secretion by
      modulating adrenergic alpha2 receptors through the mTOR pathway. The role of the
      mTOR pathway in metabolic homeostasis led us to a second important finding in
      this study; retrospective analysis of clinical data showed that co-administration
      of rapamycin and clonidine was associated with an increased incidence of new
      onset diabetes in renal transplantation patients over those receiving rapamycin
      alone. We believe that inhibition of mTOR by rapamycin along with activation of
      adrenergic alpha2 receptors by clonidine represents a double-hit to pancreatic
      islets that synergistically disturbs glucose homeostasis. This new insight may
      have important implications for the clinical management of renal transplant
      patients.

PMID- 22645145
TI  - Tracing determinants of dual substrate specificity in glycoside hydrolase family
      5.
AB  - Enzymes are traditionally viewed as having exquisite substrate specificity;
      however, recent evidence supports the notion that many enzymes have evolved
      activities against a range of substrates. The diversity of activities across
      glycoside hydrolase family 5 (GH5) suggests that this family of enzymes may
      contain numerous members with activities on multiple substrates. In this study,
      we combined structure- and sequence-based phylogenetic analysis with biochemical
      characterization to survey the prevalence of dual specificity for glucan- and
      mannan-based substrates in the GH5 family. Examination of amino acid profile
      differences between the subfamilies led to the identification and subsequent
      experimental confirmation of an active site motif indicative of dual specificity.
      The motif enabled us to successfully discover several new dually specific members
      of GH5, and this pattern is present in over 70 other enzymes, strongly suggesting
      that dual endoglucanase-mannanase activity is widespread in this family. In
      addition, reinstatement of the conserved motif in a wild type member of GH5
      enhanced its catalytic efficiency on glucan and mannan substrates by 175 and
      1,600%, respectively. Phylogenetic examination of other GH families further
      indicates that the prevalence of enzyme multispecificity in GHs may be greater
      than has been experimentally characterized. Single domain multispecific GHs may
      be exploited for developing improved enzyme cocktails or facile engineering of
      microbial hosts for consolidated bioprocessing of lignocellulose.

PMID- 22645147
TI  - The forkhead box transcription factor FOXC1 promotes breast cancer invasion by
      inducing matrix metalloprotease 7 (MMP7) expression.
AB  - Therapeutic options for treatment of basal-like breast cancers are limited and
      identification of molecular targets for novel therapies to treat this aggressive
      cancer is urgently needed. Recently, FOXC1, a forkhead box transcription factor,
      was identified as a functionally important biomarker of breast cancer
      aggressiveness and the basal-like breast cancer subtype. However, the mechanism
      through which FOXC1 controls aggressiveness of basal-like breast cancer remains
      to be elucidated. Here, we identify matrix metalloprotease 7 (MMP7) as a key
      downstream effector of FOXC1-mediated invasiveness. Expression of FOXC1 and MMP7
      is significantly correlated in breast cancer samples and cell lines at both the
      mRNA and protein levels. Transient expression of FOXC1 in nontransformed mammary
      epithelial cell lines resulted in significantly increased expression of MMP7 and
      an MMP7-dependent increase in invasiveness. In reciprocal experiments, silencing
      endogenous FOXC1 in basal-like breast cancer cell lines resulted in decreased
      expression of MMP7 without decreased expression of other matrix
      metalloproteinases. We also demonstrate that elevated co-expression of FOXC1 and
      MMP7 is an independent predictor of patient outcome in multivariate analyses of
      two breast cancer patient cohorts. Together, our findings identify MMP7 as a
      novel mechanism through which FOXC1 may regulate the basal-like breast cancer
      invasive phenotype and the propensity of these cancers to metastasize.
      Furthermore, our findings demonstrate for the first time a correlation between
      MMP7 expression and basal-like breast cancers, suggesting that MMP7 may be a
      useful therapeutic target for treatment of this disease.

PMID- 22645146
TI  - Inducible and conditional deletion of extracellular signal-regulated kinase 5
      disrupts adult hippocampal neurogenesis.
AB  - Recent studies have led to the exciting idea that adult-born neurons in the
      dentate gyrus of the hippocampus may play a role in hippocampus-dependent memory
      formation. However, signaling mechanisms that regulate adult hippocampal
      neurogenesis are not well defined. Here we report that extracellular signal
      regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinase
      family, is selectively expressed in the neurogenic regions of the adult mouse
      brain. We present evidence that shRNA suppression of ERK5 in adult hippocampal
      neural stem/progenitor cells (aNPCs) reduces the number of neurons while
      increasing the number of cells expressing markers for stem/progenitor cells or
      proliferation. Furthermore, shERK5 attenuates both transcription and neuronal
      differentiation mediated by Neurogenin 2, a transcription factor expressed in
      adult hippocampal neural progenitor cells. By contrast, ectopic activation of
      endogenous ERK5 signaling via expression of constitutive active MEK5, an upstream
      activating kinase for ERK5, promotes neurogenesis in cultured aNPCs and in the
      dentate gyrus of the mouse brain. Moreover, neurotrophins including NT3 activate
      ERK5 and stimulate neuronal differentiation in aNPCs in an ERK5-dependent manner.
      Finally, inducible and conditional deletion of ERK5 specifically in the
      neurogenic regions of the adult mouse brain delays the normal progression of
      neuronal differentiation and attenuates adult neurogenesis in vivo. These data
      suggest ERK5 signaling as a critical regulator of adult hippocampal neurogenesis.

PMID- 22645148
TI  - Chicken ovalbumin upstream promoter transcription factor II regulates renin gene
      expression.
AB  - This study aimed to investigate the possible involvement of the orphan nuclear
      receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII)
      in the regulation of renin gene expression. COUP-TFII colocalized with renin in
      the juxtaglomerular cells of the kidney, which are the main source of renin in
      vivo. Protein-DNA binding studies demonstrated that COUP-TFII binds to an
      imperfect direct repeat COUP-TFII recognition sequence (termed hereafter proxDR)
      in the proximal renin promoter. Because cAMP signaling plays a central role in
      the control of the renin gene expression, we suggested that COUP-TFII may
      modulate this cAMP effect. Accordingly, knockdown of COUP-TFII in the clonal
      renin-producing cell lines As4.1 and Calu-6 diminished the stimulation of the
      renin mRNA expression by cAMP agonists. In addition, the mutation of the proxDR
      element in renin promoter reporter gene constructs abrogated the inducibility by
      cAMP. The proxDR sequence was found to be necessary for the function of a
      proximal renin promoter cAMP-response element (CRE). Knockdown of COUP-TFII or
      cAMP-binding protein (CREB), which is the archetypal transcription factor binding
      to CRE, decreased the basal renin gene expression. However, the deficiency of
      COUP-TFII did not further diminish the renin expression when CREB was knocked
      down. In agreement with the cell culture studies, mutant mice deficient in COUP
      TFII have lower renin expression than their control strain. Altogether our data
      show that COUP-TFII is involved in the control of renin gene expression.

PMID- 22645150
TI  - Comparison of clinical outcome of breast cancer patients with T1-2 tumor and one
      to three positive nodes with or without postmastectomy radiation therapy.
AB  - OBJECTIVE: The value of postmastectomy radiation therapy for breast cancer
      patients with T1-2 tumor and one to three positive nodes remains controversial.
      The purpose of this retrospective study was to compare the clinical outcomes of
      breast cancer patients with T1-2 and one to three positive nodes with and without
      postmastectomy radiation therapy. METHODS: Between May 1990 and June 2008, of 318
      breast cancer patients with T1-2 and one to three positive nodes who had
      undergone modified radical mastectomy, 163 received postmastectomy radiation
      therapy and 155 did not. The clinico-pathologic characteristics were analyzed for
      clinical outcomes including loco-regional recurrence, distant metastasis, disease
      free survival and overall survival. RESULTS: During the median follow-up period
      of 102 months, the clinical outcomes in postmastectomy radiation therapy versus
      no-postmastectomy radiation therapy groups were as follows: loco-regional
      recurrence rate (3.1 versus 11.0%, P= 0.006); distant metastasis rate (20.9
      versus 27.7%, P= 0.152); 10-year disease-free survival rate (73.8 versus 61.3%,
      P= 0.001); and 10-year overall survival rate (82.1 versus 76.1%, P= 0.239).
      Through a multivariate analysis, a positive nodal ratio of >=25% (hazard ratio=
      4.571, P= 0.003) and positive lymphovascular invasion (hazard ratio= 2.738, P=
      0.028) were found to be independent poor prognostic predictors of loco-regional
      recurrence. The reduction in loco-regional recurrence (hazard ratio= 0.208, P=
      0.004) by postmastectomy radiation therapy was found to be significant.
      CONCLUSIONS: On the basis of our results, postmastectomy radiation therapy is
      highly recommended for breast cancer patients with T1-2 and one to three positive
      nodes, especially for high-risk subgroups with a positive nodal ratio of >=25%
      and positive lymphovascular invasion, not only for reducing loco-regional
      recurrence but also for improving disease-free survival.

PMID- 22645151
TI  - Porcine circovirus type 2 infection before and during an outbreak of postweaning
      multisystemic wasting syndrome on a pig farm in the UK.
AB  - The presence of porcine circovirus type 2 (PCV-2) and other pathogens before and
      during an outbreak of postweaning multisystemic wasting syndrome (PWMS) in pigs
      is evaluated in this study. At the time of the outbreak on a large commercial pig
      farm in the UK, serum samples and data were collected in two independent on-going
      research projects, one in weaned pigs and the other in sows. Serum samples of
      growing pigs and sows were PCV-2-antibody and PCR positive before and during the
      PMWS outbreak. Upon sequencing, PCV-2 isolates collected before the outbreak were
      identified as PCV-2a, and isolates collected during the outbreak were identified
      as PCV-2b, suggesting a shift of PCV-2 genotypes present on the farm. Pigs in the
      weaner study were from sows originating from different breeders and an
      association of sow origin and PCV-2 serostatus in offspring was found. Further,
      pigs had higher odds to be PCV-2 antigen positive if the sow was PCV-2 antibody
      positive around farrowing, the sow was of higher parity, and were less likely to
      test antigen positive if the sow was sourced from a particular breeder. The
      findings of this study highlight the potential role of the immune status of the
      sow on the occurrence of PMWS.

PMID- 22645149
TI  - Novel anti-inflammatory activity of epoxyazadiradione against macrophage
      migration inhibitory factor: inhibition of tautomerase and proinflammatory
      activities of macrophage migration inhibitory factor.
AB  - Macrophage migration inhibitory factor (MIF) is responsible for proinflammatory
      reactions in various infectious and non-infectious diseases. We have investigated
      the mechanism of anti-inflammatory activity of epoxyazadiradione, a limonoid
      purified from neem (Azadirachta indica) fruits, against MIF. Epoxyazadiradione
      inhibited the tautomerase activity of MIF of both human (huMIF) and malaria
      parasites (Plasmodium falciparum (PfMIF) and Plasmodium yoelii (PyMIF)) non
      competitively in a reversible fashion (K(i), 2.11-5.23 MUm). Epoxyazadiradione
      also significantly inhibited MIF (huMIF, PyMIF, and PfMIF)-mediated
      proinflammatory activities in RAW 264.7 cells. It prevented MIF-induced
      macrophage chemotactic migration, NF-kappaB translocation to the nucleus, up
      regulation of inducible nitric-oxide synthase, and nitric oxide production in RAW
      264.7 cells. Epoxyazadiradione not only exhibited anti-inflammatory activity in
      vitro but also in vivo. We tested the anti-inflammatory activity of
      epoxyazadiradione in vivo after co-administering LPS and MIF in mice to mimic the
      disease state of sepsis or bacterial infection. Epoxyazadiradione prevented the
      release of proinflammatory cytokines such as IL-1alpha, IL-1beta, IL-6, and TNF
      alpha when LPS and PyMIF were co-administered to BALB/c mice. The molecular basis
      of interaction of epoxyazadiradione with MIFs was explored with the help of
      computational chemistry tools and a biological knowledgebase. Docking simulation
      indicated that the binding was highly specific and allosteric in nature. The well
      known MIF inhibitor (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid
      methyl ester (ISO-1) inhibited huMIF but not MIF of parasitic origin. In
      contrast, epoxyazadiradione inhibited both huMIF and plasmodial MIF, thus bearing
      an immense therapeutic potential against proinflammatory reactions induced by MIF
      of both malaria parasites and human.

PMID- 22645152
TI  - Residual effects of Mycobacterium avium infection on susceptibility of sheep to
      copper toxicity and efficacy of treatment with tetrathiomolybdate.
AB  - Posthaemolytic copper poisoning (post-HCP) in one of six, one-year-old,
      uninfected sheep (group O) on a Mycobacterium avium experiment prompted an
      evaluation of copper status and hepatotoxicity in 17 surviving cohorts. Group O
      had higher mean plasma Cu and delta-glutamyl transferase (GGT) activity and more
      variable bile acid (BA) concentrations and glutamate dehydrogenase activities
      (GDH) than two groups infected with M avium soon after birth. Ammonium
      tetrathiomolybdate (TTM; 3 x 1.7 mg/kg LW) was given subcutaneously over seven
      days and the pelleted, complete diet replaced by hay, low in copper. Plasma BA
      immediately declined and was followed by GDH, but erythrocyte superoxide
      dismutase activity (ESOD) became severely inhibited and took 18 days to recover.
      Plasma BA and GDH rose sharply after 18 days in uninfected sheep and they became
      hypercupraemic. TTM treatment was repeated from day 42 and had removed all group
      differences by day 110 but only after further inhibition of ESOD. M avium
      infections probably lessened the severity of pre-HCP by reducing copper retention
      but may predispose grazing livestock to hypocupraemia. The capacity of TTM to
      reduce liver Cu has probably been overestimated and side effects on cuproenzyme
      activity underestimated.

PMID- 22645153
TI  - Risk of bovine tuberculosis for cattle sold out from herds during 2005 in
      Ireland.
AB  - A retrospective cohort study was conducted to determine the risk of bovine
      tuberculosis (TB) among animals sold out from herds that were free to trade
      animals during the year 2005 according to their bovine TB testing history during
      the year 2005. The present study sample comprised of 338,960 animals, of which
      124,360 animals were sold out from herds that were restricted from trading at
      some stage during 2005 (bovine TB 'exposed') and 214,600 animals that were sold
      from herds which did not have their trading status withdrawn in 2005 (bovine TB
      'non-exposed'). The overall risk of a diagnosis of bovine TB during the two-year
      period after the animals were sold out was 0.69 per cent. The odds of bovine TB
      were 1.91 higher for animals sold out from bovine TB 'exposed' herds compared
      with animals sold out from bovine TB 'non-exposed' herds (OR 95 per cent CI: 1.76
      to 2.07, P<0.0001). Ten per cent of animals identified during field surveillance
      with bovine TB did so less than two months after being sold out in 2005, and
      similarly, 10 per cent of the animals classified as bovine TB positive by finding
      a bovine TB lesion at slaughter did so within 25 days (or less) of being sold out
      in 2005.

PMID- 22645154
TI  - Detection of Mycoplasma hyopneumoniae in nasal swabs sampled from pig farmers.

PMID- 22645155
TI  - Pulmonary hypertension associated with Ehrlichia canis infection in a dog.

PMID- 22645156
TI  - Molluscum contagiosum in two donkeys.

PMID- 22645158
TI  - Heart rate variability parameters of myxomatous mitral valve disease in dogs with
      and without heart failure obtained using 24-hour Holter electrocardiography.
AB  - Time-domain heart rate variability (HRV) parameters and the correlation between
      echocardiography and Holter examinations in dogs with myxomatous mitral valve
      disease (MMVD) were determined. Holter examination was also performed at
      different time frames: an entire 24-hour period, a four-hour period during sleep,
      and a four-hour period while awake. Ten healthy (control group) and 28 MMVD dogs,
      15 with and 13 without heart failure, were evaluated. The SDANN (sd of the mean
      normal RR intervals for all five-minute segments during 24-hour Holter) and
      pNN(50) (percentage of differences between adjacent normal RR intervals that are
      >50 ms computed over 24-hour Holter) variables were significantly lower in the
      dogs with MMVD heart failure. The differences in HRV between the groups were only
      detected during the 24-hour evaluation period (P<0.05). There were high
      correlations (canonical analysis) between Holter and echocardiography
      examinations when considering pNN(50), SDANN, and LA/AO (left atrial to aortic
      root ratio) (r=0.92; P<0.05), indicating that both are important in evaluating
      MMVD dogs. SDANN and pNN(50) are measures of parasympathetic control of the
      heart, and thus, it is possible to infer that the MMVD dogs exhibit
      parasympathetic withdrawal during the development of heart failure.

PMID- 22645157
TI  - Identification of Tenacibaculum maritimum strains from marine farmed fish in
      Greece.

PMID- 22645159
TI  - Ultrasonographic findings in two calves with bone sequestration of an extremity.

PMID- 22645160
TI  - Genetic evidence of subaortic stenosis in the Newfoundland dog.
AB  - Subaortic stenosis (SAS) is a cardiac disorder with a narrowing of the descending
      aorta below the left ventricular outflow tract of the heart. It occurs in several
      species and breeds. The Newfoundland is one of the dog breeds where it is more
      common and usually leads to death at early adulthood. It is still discussed to
      which extent SAS has a genetic background and what its mode of inheritance could
      be. Extensive pedigree data comprising more than 230,000 Newfoundland dogs from
      the European and North American population reaching back to the 19th century
      including 6023 dogs with a SAS diagnosis were analysed for genetic factors
      influencing SAS affection. The incidence and prevalence of SAS in the analysed
      Newfoundland population sample were much higher than those reported in previous
      studies on smaller population samples. Assuming that some SAS-affected dogs
      remained undiscovered or were not reported, these figures may even be
      underestimated. SAS-affected Newfoundland dogs were more often inbred and closer
      related to each other than unaffected dogs, which is an indicator for a genetic
      background of SAS. The sex had no significant impact on SAS affectedness,
      pointing at an autosomal inheritance. The only simple mode of inheritance that
      fitted the data well was autosomal codominant with lethal homozygosity and a
      penetrance of 1/3 in the heterozygotes.

PMID- 22645161
TI  - Economic consequences of immediate or delayed insemination of a cow in oestrus.
AB  - Most dairy farmers are not certain whether immediate insemination or delaying the
      insemination is the best economic decision for a cow in oestrus. A model was
      developed for determining, based on herd and cow characteristics, the economic
      consequences of immediate or delayed insemination. The model was based on
      literature information and expert knowledge. In the model, the oestrus detection
      and conception rates were made cow-specific. The utility of the model was
      illustrated using a standard cow and data on 90 cows in oestrus (provided by 10
      Dutch dairy farmers). The model suggested that for the majority of cows, the best
      decision is to immediately inseminate the cow in oestrus, but for most heifers
      with a flatter lactation curve the best decision was to delay the insemination.
      The economic effect of delaying the insemination was however small, on average 
      ?18 per cow per year. Immediate insemination of an individual cow did result in
      relatively low economic benefits, but for a whole herd they can be substantial.
      This model can be used by farmers to help making the best economic decision for a
      cow in oestrus.

PMID- 22645162
TI  - Mental contrasting and the self-regulation of responding to negative feedback.
AB  - Mentally contrasting a desired future with impeding reality promotes goal pursuit
      when expectations of success are high and curbs goal pursuit when expectations of
      success are low. Four studies tested whether mental contrasting affects responses
      to goal-relevant negative feedback. Mental contrasting promoted the processing of
      negative feedback (Studies 1 and 2), which in turn helped participants to form
      plans beneficial for goal pursuit (Study 2). Mental contrasting also protected
      the self-view of competence against negative feedback (Study 3) and facilitated
      beneficial attributions for negative feedback (Study 4). All effects occurred in
      line with expectations of success. These results suggest that mental contrasting
      regulates effective responses to negative feedback by bringing goal pursuit in
      line with expectations of success.

PMID- 22645163
TI  - Social identity complexity and immigrants' attitude toward the host nation: the
      intersection of ethnic and religious group identification.
AB  - Social identity complexity refers to individual differences in the
      interrelationships among multiple ingroup identities. The present research
      conducted in the Netherlands examines social identity complexity in relation to
      Muslim immigrants' national identification and the attitude toward the host
      majority. Three studies are reported that focused on the interrelationship
      between ethnicity and religion and examined social identity complexity in
      different ways. Study 1 showed that lower social identity complexity is
      associated with lower national identification. Studies 2 and 3 examined the
      interaction between ethnic and religious group identification. For Muslim
      identifiers, higher ethnic identification was related to lower national
      identification and higher ingroup bias (Studies 2) and lower endorsement of
      national liberal practices (Study 3). In contrast, for those who did not strongly
      identify with Muslims, higher ethnic identification was associated with higher
      national identification, stronger endorsement of Dutch liberal practices, and
      more positive stereotypes about the Dutch outgroup (Study 3).

PMID- 22645164
TI  - Self-compassion increases self-improvement motivation.
AB  - Can treating oneself with compassion after making a mistake increase self
      improvement motivation? In four experiments, the authors examined the hypothesis
      that self-compassion motivates people to improve personal weaknesses, moral
      transgressions, and test performance. Participants in a self-compassion
      condition, compared to a self-esteem control condition and either no intervention
      or a positive distraction control condition, expressed greater incremental
      beliefs about a personal weakness (Experiment 1); reported greater motivation to
      make amends and avoid repeating a recent moral transgression (Experiment 2);
      spent more time studying for a difficult test following an initial failure
      (Experiment 3); exhibited a preference for upward social comparison after
      reflecting on a personal weakness (Experiment 4); and reported greater motivation
      to change the weakness (Experiment 4). These findings suggest that, somewhat
      paradoxically, taking an accepting approach to personal failure may make people
      more motivated to improve themselves.

PMID- 22645165
TI  - On the role of attention and emotion in morality: attentional control modulates
      unrelated disgust in moral judgments.
AB  - The emotion of disgust can influence people's moral judgments, even if this
      emotion objectively is unrelated to the moral judgment in question. The present
      work demonstrates that attentional control regulates this effect. In three
      studies, disgust was induced. In an unrelated part of the studies, participants
      then judged a moral transgression. Disgust resulted in more severe moral
      judgments when attentional control (either measured by means of individual
      predisposition or manipulated with experimental control) was weak as opposed to
      strong (Studies 1-3). Findings further showed that attentional control mediated
      the positive relation between the intensity of participants' disgust responses
      and the severity of their moral judgments (Study 2). Moreover, attentional
      control has its effects through the regulation of affective processing (Study 3).
      Taken together, the findings suggest that unrelated influences of disgust on
      moral judgments are contingent on the attention system.

PMID- 22645166
TI  - An integrated open framework for thermodynamics of reactions that combines
      accuracy and coverage.
AB  - MOTIVATION: The laws of thermodynamics describe a direct, quantitative
      relationship between metabolite concentrations and reaction directionality.
      Despite great efforts, thermodynamic data suffer from limited coverage, scattered
      accessibility and non-standard annotations. We present a framework for unifying
      thermodynamic data from multiple sources and demonstrate two new techniques for
      extrapolating the Gibbs energies of unmeasured reactions and conditions. RESULTS:
      Both methods account for changes in cellular conditions (pH, ionic strength,
      etc.) by using linear regression over the DeltaG(?) of pseudoisomers and
      reactions. The Pseudoisomeric Reactant Contribution method systematically infers
      compound formation energies using measured K' and pK(a) data. The Pseudoisomeric
      Group Contribution method extends the group contribution method and achieves a
      high coverage of unmeasured reactions. We define a continuous index that predicts
      the reversibility of a reaction under a given physiological concentration range.
      In the characteristic physiological range 3MUM-3mM, we find that roughly half of
      the reactions in Escherichia coli's metabolism are reversible. These new tools
      can increase the accuracy of thermodynamic-based models, especially in non
      standard pH and ionic strengths. The reversibility index can help modelers decide
      which reactions are reversible in physiological conditions. AVAILABILITY: Freely
      available on the web at: http://equilibrator.weizmann.ac.il. Website implemented
      in Python, MySQL, Apache and Django, with all major browsers supported. The
      framework is open-source (code.google.com/p/milo-lab), implemented in pure Python
      and tested mainly on Linux. CONTACT: ron.milo@weizmann.ac.il SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 22645167
TI  - A common ancestry for BAP1 and Uch37 regulators.
AB  - SUMMARY: To reveal how the polycomb repressive-deubiquitinase (PR-DUB) complex
      controls substrate selection specificity, we undertook a detailed computational
      sequence analysis of its components: additional sex combs like 1 (ASXL1) and
      BRCA1-associated protein 1 (BAP1) proteins. This led to the discovery of two
      previously unrecognized domains in ASXL1: a forkhead (winged-helix) DNA-binding
      domain and a deubiquitinase adaptor domain shared with two regulators of
      ubiquitin carboxyl-terminal hydrolase 37 (Uch37), namely adhesion regulating
      molecule 1 (ADRM1) and nuclear factor related to kappaB (NFRKB). Our analysis
      demonstrates a common ancestry for BAP1 and Uch37 regulators in PR-DUB, INO80
      chromatin remodelling and proteosome complexes. CONTACT:
      luis.sanchezpulido@dpag.ox.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 22645168
TI  - AS-EAST: a functional annotation tool for putative proteins encoded by
      alternatively spliced transcripts.
AB  - SUMMARY: Alternative Splicing Effects ASsessment Tools (AS-EAST) is an online
      tool for the functional annotation of putative proteins encoded by transcripts
      generated by alternative splicing (AS). When provided with a transcript sequence,
      AS-EAST identifies regions altered by AS events in the putative protein sequence
      encoded by the transcript. Users can evaluate the predicted function of the
      putative protein by inspecting whether functional domains are included in the
      altered regions. Moreover, users can infer the loss of inter-molecular
      interactions in the protein network according to whether the AS events affect
      interaction residues observed in the 3D structure of the reference isoform. The
      information obtained from AS-EAST will help to design experimental analyses for
      the functional significance of novel splice isoforms. AVAILABILITY: The online
      tool is freely available at http://as-alps.nagahama-i-bio.ac.jp/ASEAST/. CONTACT:
      m_shionyu@nagahama-i-bio.ac.jp.

PMID- 22645169
TI  - Gene polymorphisms and fiber-type composition of human skeletal muscle.
AB  - The ability to perform aerobic or anaerobic exercise varies widely among
      individuals, partially depending on their muscle-fiber composition. Variability
      in the proportion of skeletal-muscle fiber types may also explain marked
      differences in aspects of certain chronic disease states including obesity,
      insulin resistance, and hypertension. In untrained individuals, the proportion of
      slow-twitch (Type I) fibers in the vastus lateralis muscle is typically around
      50% (range 5-90%), and it is unusual for them to undergo conversion to fast
      twitch fibers. It has been suggested that the genetic component for the observed
      variability in the proportion of Type I fibers in human muscles is on the order
      of 40-50%, indicating that muscle fiber-type composition is determined by both
      genotype and environment. This article briefly reviews current progress in the
      understanding of genetic determinism of fiber-type proportion in human skeletal
      muscle. Several polymorphisms of genes involved in the calcineurin-NFAT pathway,
      mitochondrial biogenesis, glucose and lipid metabolism, cytoskeletal function,
      hypoxia and angiogenesis, and circulatory homeostasis have been associated with
      fiber-type composition. As muscle is a major contributor to metabolism and
      physical strength and can readily adapt, it is not surprising that many of these
      gene variants have been associated with physical performance and athlete status,
      as well as metabolic and cardiovascular diseases. Genetic variants associated
      with fiber-type proportions have important implications for our understanding of
      muscle function in both health and disease.

PMID- 22645170
TI  - Case study: nutritional strategies of a cyclist with celiac disease during an
      ultraendurance race.
AB  - Food intolerance is becoming increasingly prevalent, and increasing numbers of
      athletes have celiac disease. This poses challenges as dietary recommendations
      for exercise are largely based on gluten-containing carbohydrate-rich foods. The
      K4 cycle race covers 384 km around the Coromandel Peninsula, New Zealand. Lack of
      sleep, darkness, and temperature variations pose a number of nutritional
      challenges. Limited food choices present those with celiac disease with even
      greater challenges. This case study describes the intakes of one such athlete
      during training and competing in the K4. Nutritional intakes were obtained during
      training using weighed-food records and during the race via dietary recall and
      the weighing of foods pre- and post-race. As simple substitution of gluten
      containing foods for gluten-free foods leads to increased energy intake,
      alternatives need to be considered. During the race, insufficient energy was
      consumed to meet the nutritional guidelines for endurance performance. This was
      probably due to the nature of the course, racing conditions, the consistency of
      gluten-free food, and, toward the end of the race, sensory-specific satiety.

PMID- 22645171
TI  - Effects of a Lactobacillus salivarius probiotic intervention on infection, cold
      symptom duration and severity, and mucosal immunity in endurance athletes.
AB  - The purpose of this study was to examine the effects of a probiotic supplement
      during 4 mo of spring training in men and women engaged in endurance-based
      physical activities on incidence of upper respiratory tract infections (URTI) and
      mucosal immune markers. Sixty-six highly active individuals were randomized to
      probiotic (n = 33) or placebo (n = 33) groups and, under double-blind procedures,
      received probiotic (PRO: Lactobacillus salivarius, 2 * 1010 bacterium colony
      forming units) or placebo (PLA) daily for 16 wk. Resting blood and saliva samples
      were collected at baseline and after 8 and 16 wk. Weekly training and illness
      logs were kept. Fifty-four subjects completed the study (n = 27 PRO, n = 27 PLA).
      The proportion of subjects on PRO who experienced 1 or more wk with URTI symptoms
      was not different from that of those on PLA (PRO .58, PLA .59; p = .947). The
      number of URTI episodes was similar in the 2 groups (PRO 1.6 +/- 0.3, PLA 1.4 +/-
      0.3; p = .710). Severity and duration of symptoms were not significantly
      different between treatments. Blood leukocyte, neutrophil, monocyte, and
      lymphocyte counts; saliva IgA; and lysozyme concentrations did not change over
      the course of the study and were not different on PRO compared with PLA. Regular
      ingestion of L. salivarius does not appear to be beneficial in reducing the
      frequency of URTI in an athletic cohort and does not affect blood leukocyte
      counts or levels of salivary antimicrobial proteins during a spring period of
      training and competition.

PMID- 22645172
TI  - Influence of artistic gymnastics on iron nutritional status and exercise-induced
      hemolysis in female athletes.
AB  - This study evaluates the relationship between body iron losses and gains in
      artistic gymnastics female athletes. It shows that despite the low iron intake
      and exercise-induced hemolysis, iron deficiency or iron-deficiency anemia does
      not occur, but partial changes in the hematological profile do. The hypothesis
      that gymnasts' nutritional behavior contributes to anemia, which may be
      aggravated by exercise-induced hemolysis, led to this cross-sectional study,
      conducted with 43 female artistic gymnasts 6-16 yr old. The control group was
      formed by 40 nontraining girls, paired by age. Hemogram, serum iron, ferritin,
      soluble transferrin receptor, haptoglobin, total and fractional bilirubin, Type I
      urine, and parasitologic and occult fecal blood tests were evaluated. The
      athletes presented mean hematimetric and serum iron values (p = .020) higher than
      those of the control group. The bilirubin result discarded any hemolytic
      alteration in both groups. The haptoglobin results were lower in the athlete
      group (p = .002), confirming the incidence of exercise-induced hemolysis. Both
      groups presented low iron intake. The results suggest that artistic gymnastics
      practice leads to exercise-induced hemolysis and partially changes the
      hematological profile, although not causing iron deficiency or iron-deficiency
      anemia, even in the presence of low iron intake.

PMID- 22645173
TI  - Current role and future directions of hybrid repair of thoracoabdominal aortic
      aneurysms.
AB  - Hybrid procedures were introduced as a less invasive alternative to open
      conventional repair, avoiding thoracotomy, single-lung ventilation, and in many
      patients, aortic cross-clamping. Despite these potential advantages over open
      repair, results of hybrid repair have varied in the literature, with several
      reports indicating high morbidity and mortality rates. It is likely that once
      fenestrated and branched endografts receive approval from the Food and Drug
      Administration for clinical use, indications for hybrid repair of complex aortic
      aneurysms will further diminish. This article summarizes the current state of the
      art on patient selection, techniques, and results of hybrid procedures for the
      treatment of thoracoabdominal aortic aneurysms.

PMID- 22645174
TI  - Effects of water immersion on posttraining recovery in Australian footballers.
AB  - PURPOSE: The authors investigated the efficacy of a single exposure to 14 min of
      cold-water immersion (COLD) and contrast water therapy (CWT) on posttraining
      recovery in Australian football (AF). METHOD: Fourteen AF players participated in
      3 wk of standardized training. After week 1 training, all players completed a
      passive recovery (PAS). During week 2, COLD or CWT was randomly assigned. Players
      undertook the opposing intervention in week 3. Repeat-sprint ability (6 * 20 m),
      countermovement and squat jumps, perceived muscle soreness, and fatigue were
      measured pretraining and over 48 h posttraining. RESULTS: Immediately
      posttraining, groups exhibited similar performance and psychometric declines. At
      24 h, repeat-sprint time had deteriorated by 4.1% for PAS and 1.0% for CWT but
      was fully restored by COLD (0.0%). At 24 and 48 h, both COLD and CWT attenuated
      changes in mean muscle soreness, with COLD (0.6 +/- 0.6 and 0.0 +/- 0.4) more
      effective than CWT (1.9 +/- 0.7 and 1.0 +/- 0.7) and PAS having minimal effect
      (5.5 +/- 0.6 and 4.0 +/- 0.5). Similarly, after 24 and 48 h, COLD and CWT both
      effectively reduced changes in perceived fatigue, with COLD (0.6 +/- 0.6 and 0.0
      +/- 0.6) being more successful than CWT (0.8 +/- 0.6 and 0.7 +/- 0.6) and PAS
      having the smallest effect (2.2 +/- 0.8 and 2.4 +/- 0.6). CONCLUSIONS: AF
      training can result in prolonged physical and psychometric deficits persisting
      for up to 48 h. For restoring physical-performance and psychometric measures,
      COLD was more effective than CWT, with PAS being the least effective. Based on
      these results the authors recommend that 14 min of COLD be used after AF
      training.

PMID- 22645175
TI  - Speed and countermovement-jump characteristics of elite female soccer players,
      1995-2010.
AB  - PURPOSE: The purpose of this investigation was to compare sprint and
      countermovement-jump (CMJ) performance among female competitive soccer players as
      a function of performance level, field position, and age. In addition, the
      authors wanted to quantify the evolution of these physical characteristics among
      elite players over a 15-y period. METHODS: 194 female elite players (22+/- 4.1 y,
      63 +/- 5.6 kg), including an Olympic winning squad, tested 40-m sprint with
      electronic timing and CMJ on a force platform at the Norwegian Olympic training
      center from 1995 to 2010. RESULTS: Moderate to large velocity differences across
      performance levels and positions were observed. National-team players were 2%
      faster than 1st-division players (P = .027, d = 0.5) and 5% faster than 2nd
      division players (P < .001, d = 1.3) over 0-20 m. National-team players jumped 8
      9% higher than 1st-division players (P = .001, d = 0.6) and junior elite players
      (P = .023, d = 0.5). Forwards were 3-4% faster than midfielders (P < .001, d =
      0.8) and goalkeepers (P = .003, d = 0.9) over 0-20 m. No differences in velocity
      or CMJ height were observed among the age categories. Players from 2006-2010 were
      2% faster (P < .05, d = 0.6) than players from 1995-1999 over 20 m, whereas no
      differences in 20- to 40-m velocity or CMJ performance were observed.
      CONCLUSIONS: This study provides effect-magnitude estimates for the influence of
      performance level, age, and player position on sprint and CMJ performance in
      female soccer players. While 20- to 40-m velocity and CMJ performance have
      remained stable over the time, there has been a moderate but positive development
      in 0- to 20-m velocity among elite performers.

PMID- 22645176
TI  - Survivin is highly expressed in CD34(+)38(-) leukemic stem/progenitor cells and
      predicts poor clinical outcomes in AML.
AB  - Survivin, a member of the inhibitors of apoptosis protein family, plays important
      roles in cell proliferation and survival and is highly expressed in various
      malignancies, including leukemias. To better understand its role in acute myeloid
      leukemia (AML), we profiled survivin expression in samples obtained from 511
      newly diagnosed AML patients and in CD34(+)38(-) AML stem/progenitor cells using
      a validated reverse-phase protein array; we correlated its levels with clinical
      outcomes and with levels of other proteins in the same sample set. We found that
      survivin levels were higher in bone marrow than in paired peripheral blood
      leukemic cells (n = 140, P = .0001) and that higher survivin levels significantly
      predicted shorter overall (P = .016) and event-free (P = .023) survival in
      multivariate Cox model analysis. Importantly, survivin levels were significantly
      higher in CD34(+)38(-) AML stem/progenitor cells than in bulk blasts and total
      CD34(+) AML cells (P < .05). Survivin expression correlated with the expressions
      of multiple proteins involved with cell proliferation and survival. Particularly,
      its expression strongly correlated with HIF1alpha in the stem/progenitor cell
      compartment. These results suggest that survivin is a prognostic biomarker in AML
      and that survivin, which is overexpressed in AML stem/progenitor cells, remains a
      potentially important target for leukemia therapy.

PMID- 22645178
TI  - Allogeneic hematopoietic stem cell transplantation in thalassemia major: results
      of a reduced-toxicity conditioning regimen based on the use of treosulfan.
AB  - Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent
      allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation
      combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were
      assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to
      class 3; 12 patients were adults. Twenty patients were transplanted from an HLA
      identical sibling and 40 from an unrelated donor. The cumulative incidence of
      graft failure and transplantation-related mortality was 9% and 7%, respectively.
      Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being
      14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median
      follow-up of 36 months (range, 4-72), the 5-year probability of survival and
      thalassemia-free survival are 93% and 84%, respectively. Neither the class of
      risk nor the donor used influenced outcome. This treosulfan-based preparation
      proved to be safe and effective for thalassemia patients given allogeneic HSCT.

PMID- 22645177
TI  - TCL1: a shared tumor-associated antigen for immunotherapy against B-cell
      lymphomas.
AB  - Immunotherapy with therapeutic idiotype vaccines offers promise for treatment of
      B-cell malignancies. However, identification of novel immunogenic lymphoma
      associated antigens that are universally expressed is necessary to overcome the
      barriers of patient-specific idiotype vaccines. Here, we determined whether T
      cell leukemia/lymphoma 1 (TCL1) oncoprotein encoded by the TCL1 gene could be a
      target for immunotherapy of B-cell malignancies. We show that TCL1 mRNA and
      protein are selectively expressed in normal B cells but markedly hyperexpressed
      in multiple human B-cell lymphomas, including follicular lymphoma, chronic
      lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, and
      splenic marginal zone B-cell lymphoma. We demonstrated that TCL1-specific CD8(+)
      T cells can be generated from HLA-A*0201 (HLA-A2)(+) normal donors and identified
      TCL1(71-78) (LLPIMWQL) as the minimal epitope recognized by these T cells. More
      importantly, TCL1(71-78) peptide-specific T cells were present in the peripheral
      blood and tumor-infiltrating lymphocytes of lymphoma patients, could be expanded
      in vitro, and lysed autologous tumor cells but not normal B cells in an HLA-A2
      restricted manner. Our results suggest that TCL1 is naturally processed and
      presented on the surface of lymphoma cells for recognition by cytotoxic T cells
      and can serve as a novel target for development of immunotherapeutic strategies
      against common B-cell lymphomas.

PMID- 22645179
TI  - APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase
      dependent DNA repair.
AB  - APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA
      (ssDNA), providing innate protection against retroviral replication by inducing
      deleterious dC > dU hypermutation of replication intermediates. APOBEC3G
      expression is induced in mitogen-activated lymphocytes; however, no physiologic
      role related to lymphoid cell proliferation has yet to be determined. Moreover,
      whether APOBEC3G cytidine deaminase activity transcends to processing cellular
      genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G
      levels display efficient repair of genomic DNA double-strand breaks (DSBs)
      induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G
      transiently accumulated in the nucleus in response to ionizing radiation and was
      recruited to DSB repair foci. Consistent with a direct role in DSB repair,
      inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB
      repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced
      DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an
      integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G
      multimers associate with ssDNA termini, triggering multimer disassembly to
      multiple catalytic units. These results identify APOBEC3G as a prosurvival factor
      in lymphoma cells, marking APOBEC3G as a potential target for sensitizing
      lymphoma to radiation therapy.

PMID- 22645180
TI  - FGF-2 expands murine hematopoietic stem and progenitor cells via proliferation of
      stromal cells, c-Kit activation, and CXCL12 down-regulation.
AB  - Cytokine-induced expansion of hematopoietic stem and progenitor cells (HSPCs) is
      not fully understood. In the present study, we show that whereas steady-state
      hematopoiesis is normal in basic fibroblast growth factor (FGF-2)-knockout mice,
      parathyroid hormone stimulation and myeloablative treatments failed to induce
      normal HSPC proliferation and recovery. In vivo FGF-2 treatment expanded stromal
      cells, including perivascular Nestin(+) supportive stromal cells, which may
      facilitate HSPC expansion by increasing SCF and reducing CXCL12 via mir-31 up
      regulation. FGF-2 predominantly expanded a heterogeneous population of
      undifferentiated HSPCs, preserving and increasing durable short- and long-term
      repopulation potential. Mechanistically, these effects were mediated by c-Kit
      receptor activation, STAT5 phosphorylation, and reduction of reactive oxygen
      species levels. Mice harboring defective c-Kit signaling exhibited abrogated HSPC
      expansion in response to FGF-2 treatment, which was accompanied by elevated
      reactive oxygen species levels. The results of the present study reveal a novel
      mechanism underlying FGF-2-mediated in vivo expansion of both HSPCs and their
      supportive stromal cells, which may be used to improve stem cell engraftment
      after clinical transplantation.

PMID- 22645182
TI  - Predictive value of early molecular response in patients with chronic myeloid
      leukemia treated with first-line dasatinib.
AB  - Dasatinib is effective therapy for newly diagnosed patients with chronic myeloid
      leukemia, but not all patients respond well. We analyzed the outcome of patients
      treated with dasatinib as first-line therapy to identify patients who are more
      likely to fare poorly. The 8.6% of patients who at 3 months had a BCR-ABL1/ABL1
      ratio > 10% had a significantly worse 2-year cumulative incidence of complete
      cytogenetic response (58.8% vs 96.6%, P < .001) and molecular responses than the
      remaining patients with a lower transcript levels. The predictive value of the 3
      month transcript level could be improved using the dasatinib-specific transcript
      level cut-offs, namely, 2.2%, 0.92%, and 0.57% for complete cytogenetic response,
      3 log and 4.5 log reductions in the transcript level, respectively. The study was
      registered at www.clinicaltrials.gov as #NCT01460693.

PMID- 22645181
TI  - Proteasome inhibitors in multiple myeloma: 10 years later.
AB  - Proteasome inhibition has emerged as an important therapeutic strategy in
      multiple myeloma (MM). Since the publication of the first phase 1 trials of
      bortezomib 10 years ago, this first-in-class proteasome inhibitor (PI) has
      contributed substantially to the observed improvement in survival in MM patients
      over the past decade. Although first approved as a single agent in the relapsed
      setting, bortezomib is now predominantly used in combination regimens.
      Furthermore, the standard twice-weekly schedule may be replaced by weekly
      infusion, especially when bortezomib is used as part of combination regimens in
      frontline therapy. Indeed, bortezomib is an established component of induction
      therapy for patients eligible or ineligible for autologous stem cell
      transplantation. Bortezomib has also been incorporated into conditioning regimens
      before autologous stem cell transplantation, as well as into post-ASCT
      consolidation therapy, and in the maintenance setting. In addition, a new route
      of bortezomib administration, subcutaneous infusion, has recently been approved.
      Recently, several new agents have been introduced into the clinic, including
      carfilzomib, marizomib, and MLN9708, and trials investigating these "second
      generation" PIs in patients with relapsed/refractory MMs have demonstrated
      positive results. This review provides an overview of the role of PIs in the
      treatment of MM, focusing on developments over the past decade.

PMID- 22645183
TI  - Cell lineage analysis of acute leukemia relapse uncovers the role of replication
      rate heterogeneity and microsatellite instability.
AB  - Human cancers display substantial intratumoral genetic heterogeneity, which
      facilitates tumor survival under changing microenvironmental conditions. Tumor
      substructure and its effect on disease progression and relapse are incompletely
      understood. In the present study, a high-throughput method that uses neutral
      somatic mutations accumulated in individual cells to reconstruct cell lineage
      trees was applied to hundreds of cells of human acute leukemia harvested from
      multiple patients at diagnosis and at relapse. The reconstructed cell lineage
      trees of patients with acute myeloid leukemia showed that leukemia cells at
      relapse were shallow (divide rarely) compared with cells at diagnosis and were
      closely related to their stem cell subpopulation, implying that in these
      instances relapse might have originated from rarely dividing stem cells. In
      contrast, among patients with acute lymphoid leukemia, no differences in cell
      depth were observed between diagnosis and relapse. In one case of chronic myeloid
      leukemia, at blast crisis, most of the cells at relapse were mismatch-repair
      deficient. In almost all leukemia cases, > 1 lineage was observed at relapse,
      indicating that diverse mechanisms can promote relapse in the same patient. In
      conclusion, diverse relapse mechanisms can be observed by systematic
      reconstruction of cell lineage trees of patients with leukemia.

PMID- 22645184
TI  - Serum glucose levels for predicting death in patients admitted to hospital for
      community acquired pneumonia: prospective cohort study.
AB  - OBJECTIVE: To examine whether acute dysglycaemia predicts death in people
      admitted to hospital with community acquired pneumonia. DESIGN: Multicentre
      prospective cohort study. SETTING: Hospitals and private practices in Germany,
      Switzerland, and Austria. PARTICIPANTS: 6891 patients with community acquired
      pneumonia included in the German community acquired pneumonia competence network
      (CAPNETZ) study between 2003 and 2009. MAIN OUTCOME MEASURES: Univariable and
      multivariable hazard ratios adjusted for sex, age, current smoking status,
      severity of community acquired pneumonia using the CRB-65 score (confusion,
      respiratory rate >30/min, systolic blood pressure <= 90 mm Hg or diastolic blood
      pressure <= 60 mm Hg, and age >= 65 years), and various comorbidities for death
      at 28, 90, and 180 days according to serum glucose levels on admission. RESULTS:
      An increased serum glucose level at admission to hospital in participants with
      community acquired pneumonia and no pre-existing diabetes was a predictor of
      death at 28 and 90 days. Compared with participants with normal serum glucose
      levels on admission, those with mild acute hyperglycaemia (serum glucose
      concentration 6-10.99 mmol/L) had a significantly increased risk of death at 90
      days (1.56, 95% confidence interval 1.22 to 2.01; P<0.001), and this risk
      increased to 2.37 (1.62 to 3.46; P<0.001) when serum glucose concentrations were
      >= 14 mmol/L. In sensitivity analyses the predictive value of serum glucose
      levels on admission for death was confirmed at 28 days and 90 days. Patients with
      pre-existing diabetes had a significantly increased overall mortality compared
      with those without diabetes (crude hazard ratio 2.47, 95% confidence interval
      2.05 to 2.98; P<0.001). This outcome was not significantly affected by serum
      glucose levels on admission (P = 0.18 for interaction). CONCLUSIONS: Serum
      glucose levels on admission to hospital can predict death in patients with
      community acquired pneumonia without pre-existing diabetes. Acute hyperglycaemia
      may therefore identify patients in need of intensified care to reduce the risk of
      death from community acquired pneumonia.

PMID- 22645185
TI  - Preventing overdiagnosis: how to stop harming the healthy.

PMID- 22645186
TI  - Educating tomorrow's doctors.

PMID- 22645187
TI  - Cognition matters in cardiovascular disease and heart failure.

PMID- 22645188
TI  - The Notch pathway: a crossroad between the life and death of the endothelium.

PMID- 22645189
TI  - Acute myocardial infarction and swinging heart: not always a cardiac rupture-
      haemopericardium due to infiltrative lung cancer.

PMID- 22645190
TI  - Left atrial appendage invagination during MitraClip implantation.

PMID- 22645191
TI  - Diastolic stiffness as assessed by diastolic wall strain is associated with
      adverse remodelling and poor outcomes in heart failure with preserved ejection
      fraction.
AB  - AIMS: The pathophysiology of heart failure with preserved ejection fraction
      (HFpEF) is complex but increased left ventricular (LV) diastolic stiffness plays
      a key role. A load-independent, non-invasive, direct measure of diastolic
      stiffness is lacking. The diastolic wall strain (DWS) index is based on the
      linear elastic theory, which predicts that impaired diastolic wall thinning
      reflects resistance to deformation in diastole and thus, increased diastolic
      myocardial stiffness. The objectives of this community-based study were to
      determine the distribution of this novel index in consecutive HFpEF patients and
      healthy controls, define the relationship between DWS and cardiac structure and
      function and determine whether increased diastolic stiffness as assessed by DWS
      is predictive of the outcome in HFpEF. METHODS AND RESULTS: Consecutive HFpEF
      patients (n = 327, EF >= 50%) and controls (n = 528) from the same community were
      studied. Diastolic wall strain was lower in HFpEF (0.33 +/- 0.08) than in
      controls (0.40 +/- 0.07, P < 0.001). Within HFpEF, those with DWS <= median
      (0.33) had higher LV mass index, relative wall thickness, E/e', Doppler-estimated
      LV end-diastolic pressure to LV end-diastolic volume ratio, left atrial volume
      index, and brain natriuretic peptide (BNP) levels than those with DWS > median.
      Heart failure with preserved ejection fraction patients with DWS <= median had
      higher rate of death or HF hospitalization than those with DWS > median (P =
      0.003) even after the adjustment for age, gender, log BNP, LV geometry, or log
      E/e' (P < 0.01). CONCLUSION: These data suggest that DWS, a simple index, is
      useful in assessing diastolic stiffness and that more advanced diastolic
      stiffness is associated with worse outcomes in HFpEF.

PMID- 22645192
TI  - Reduced serum levels of vasostatin-2, an anti-inflammatory peptide derived from
      chromogranin A, are associated with the presence and severity of coronary artery
      disease.
AB  - AIMS: We here investigated the endothelial effects of the chromogranin A-derived
      peptide vasostatin-2 and its relation to coronary artery disease (CAD). METHODS
      AND RESULTS: We assessed the impact of recombinant vasostatin-1 and vasostatin-2
      on tumour necrosis factor-alpha (TNFalpha)-, angiotensin II-, and oxidized low
      density lipoprotein (oxLDL)-induced expression of adhesion molecules in human
      arterial endothelial cells. Vasostatin-1 and vasostatin-2 levels were examined in
      coronary endarterectomy specimens (n= 23), atherosclerotic aortas (n= 16), non
      significant-atherosclerotic internal mammary arteries (n= 30), and non
      atherosclerotic aortas (n= 10), as well as in peripheral blood mononuclear cells
      (PBMCs) from severe CAD patients (n= 50) and healthy volunteers (n= 21). Serum
      levels of vasostatin-2 were analysed in 968 consecutive patients undergoing
      coronary angiography. Vasostatin-1 and vasostatin-2 concentration-dependently
      inhibited TNFalpha-, angiotensin II-, and oxLDL-induced expression of adhesion
      molecules; and attenuated TNFalpha-induced adhesion of U937 monocytes to
      endothelial cells. Vasostatin-2 levels were significantly decreased in
      endarterectomy samples and atherosclerotic aortas compared with non
      atherosclerotic internal mammary arteries and aortas, as well as in PBMCs of
      severe CAD patients compared with healthy controls (all P< 0.05). Serum
      vasostatin-2 levels were significantly lower in CAD patients (diameter stenosis
      >= 50%, n= 554) than in controls (normal arteries or diameter stenosis <30%, n=
      281) (P< 0.001). Its concentrations correlated with the number of diseased
      coronary arteries and Syntax score in CAD patients (all P< 0.05). At
      multivariable regression analysis, decreased vasostatin-2 levels remained
      associated with CAD when other variables were taken into account. CONCLUSION:
      Vasostatin-2 has anti-inflammatory properties and is decreased in atherosclerotic
      plaque specimens and in PBMC of CAD patients. Decreased serum vasostatin-2 levels
      are associated with the presence and severity of CAD.

PMID- 22645193
TI  - Clinical significance of variants of J-points and J-waves: early repolarization
      patterns and risk.
AB  - The variations in the electrocardiographic patterns of J-point elevations, and
      the complex of J-points and J-waves in early repolarization (ER), in conjunction
      with disparities in associated sudden cardiac death (SCD) risk, have lead to a
      recognition of the need to carefully classify the spectrum of these observations.
      Many questions about the pathogenesis of J-wave patterns, and the associated
      magnitudes of risk, remain unanswered, especially in regard to the risk
      implications in certain high-prevalence subpopulations such as athletes,
      children, and adolescents. Interest in these electrocardiography (ECG) patterns
      has grown dramatically in recent years, in large part because of the frequency
      with which these patterns are observed on routine ECGs. In this review, we
      discuss the current knowledge on the prevalence of different J-point/J-wave
      patterns and estimates of the magnitude of mortality and SCD risk associated with
      J-point elevations and J-waves, in what has become known as ER patterns.

PMID- 22645195
TI  - Changes of whole-body power, muscle function, and jump performance with prolonged
      cycling to exhaustion.
AB  - PURPOSE: To quantify how whole-body power, muscle-function, and jump-performance
      measures change during prolonged cycling and recovery and determine whether there
      are relationships between the different fatigue measures. METHODS: Ten
      competitive or recreationally active male cyclists underwent repeated 20-min
      stages of prolonged cycling at 70% VO2peak until exhaustion. Whole-body peak
      power output (PPO) was assessed using an all-out 30-s sprint 17 min into each
      cycle stage. Ratings of perceived exertion (RPE) were recorded throughout.
      Isometric and isokinetic muscle-function tests were made between cycle stages,
      over ~6 min, and during 30-min recovery. Drop-jump measures were tested at
      exhaustion and during recovery. RESULTS: PPO initially increased or was
      maintained in some subjects but fell to 81% of maximum at exhaustion. RPE was
      near maximal (18.7) at exhaustion, with the time to exhaustion related to the
      rate of rise of RPE. PPO first started to decline only when RPE exceeded 16 (ie,
      hard). Peak isometric and concentric isokinetic torque (180 degrees /s) for the
      quadriceps fell to 86% and 83% of pretest at exhaustion, respectively. In
      contrast, the peak concentric isokinetic torque (180 degrees /s) of the
      hamstrings increased by 10% before declining to 93% of maximum. Jump height fell
      to 92% of pretest at exhaustion and was correlated with the decline in PPO (r =
      .79). Muscle-function and jump-performance measures did not recover over the 30
      min postexercise rest period. CONCLUSIONS: At exhaustion, whole-body power,
      muscle-function, and jump-performance measures had all fallen by 7-19%. PPO and
      drop-jump decrements were linearly correlated and are appropriate measures of
      maximal performance.

PMID- 22645196
TI  - Game location moderates the relationship between anticipatory testosterone
      changes and athletic performance.
AB  - The authors examined the extent to which changes in testosterone concentrations
      before competition would be associated with performance among elite male hockey
      players. Saliva samples were collected on 2 noncompetition days (baseline) and
      before 2 playoff games (1 home game, 1 away game). Individual performance was
      assessed by the coaching staff after each game. Results indicated that changes in
      testosterone before competition predicted performance, but this effect was
      influenced by game location. Unexpectedly, the authors found a significant
      negative relationship between a rise in testosterone and performance for the away
      game and a nonsignificant positive relationship for the home game. These findings
      indicate that game location should be considered in studies examining the
      neuroendocrine correlates of athletic competition.

PMID- 22645194
TI  - Mid-regional pro-atrial natriuretic peptide and pro-adrenomedullin testing for
      the diagnostic and prognostic evaluation of patients with acute dyspnoea.
AB  - AIMS: The aim of this study was to assess diagnostic and prognostic value of mid
      regional pro-atrial natriuretic peptide (MR-proANP) and adrenomedullin (MR
      proADM) for the evaluation of patients presenting to the emergency department
      with acute dyspnoea. METHODS AND RESULTS: A total of 560 patients from the pro-B
      type natriuretic peptide Investigation of Dyspnoea in the Emergency Department
      were evaluated; 180 had acutely decompensated heart failure (ADHF).
      Concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), MR
      proADM, and MR-proANP were measured, and patients were followed to 4 years for
      survival. Logistic regression evaluated utility of MR-proANP in ADHF diagnosis.
      Area under the curve (AUC), multivariate Cox regression, net reclassification
      improvement, and Kaplan-Meier survival analyses were used for mortality analyses.
      Mid-regional pro-atrial natriuretic peptide was higher in patients with ADHF
      (median 329 vs. 58 pmol/L; P < 0.001), and remained an independent predictor of
      HF diagnosis even when NT-proBNP was included as a covariate (odds ratio = 4.34,
      95% CI = 2.11-8.92; P < 0.001). In time-dependent analyses, MR-proADM had the
      highest AUC for death during the first year; after 1 year, MR-proANP and NT
      proBNP had a higher AUC. Both mid-regional peptides were independently prognostic
      and reclassified risk at 1 year [MR-proANP, hazard ratio (HR) = 2.99, MR-proADM,
      HR = 2.70; both P < 0.001] and at 4 years (MR-proANP, HR = 3.12, P < 0.001; MR
      proADM, HR = 1.51, P = 0.03) and in Kaplan-Meier curves both mid-regional
      peptides were associated with death out to 4 years, individually or in a
      multimarker strategy. CONCLUSION: Among patients with acute dyspnoea, MR-proANP
      is accurate for diagnosis of ADHF, while both MR-proANP and MR-proADM are
      independently prognostic to 4 years of the follow-up.

PMID- 22645197
TI  - Historical trends in the size of US Olympic female artistic gymnasts.
AB  - The lay press, scientists, and physicians appear to believe that gymnasts are
      continually getting smaller and that their "smallness" is a health risk. PURPOSE:
      To assess the historical changes in the size and age of the US women's Olympic
      gymnastics teams from 1956 to 2008. METHODS: The official records from the US
      Olympic Committee and USA Gymnastics of Olympic team members were assessed at 2
      levels: individual height, mass, age, and body-mass index (BMI) and the team
      performance scores and rankings. Fourteen Olympic teams with a total of 106 team
      members, including the alternates, were included. Trend analyses were conducted
      using linear and polynomial models. RESULTS: Simple linear correlations indicated
      that since 1956, height, mass, age, BMI, and team Olympic rank have been
      declining. However, second-order polynomial curve fits indicated that in the last
      4 Olympic Games the members of the US women's gymnastics teams have been getting
      larger. CONCLUSION: Women Olympic gymnasts were getting smaller through
      approximately the 1980s and early 1990s. Since then the size of these gymnasts
      has increased. The minimum-age rule modifications may have played a role in
      athlete size changes along with a shift from the near dominance of the former
      communist Eastern Bloc.

PMID- 22645198
TI  - Hydration status, fluid intake, and electrolyte losses in youth soccer players.
AB  - The purpose of the study was to determine the hydration status, fluid intake, and
      electrolyte losses of 21 male professional youth soccer players (age 17.1 +/- 0.7
      y) training in a cool environment. Pretraining and posttraining measurements of
      body mass, urine (freezing-point osmolality method), and sweat concentration
      (flame-emission spectroscopy) were collected. Fourteen players were found to be
      hypohydrated before training. The amount of fluid lost due to exercise equated to
      a 1.7% loss in body mass, which equated to a gross dehydration loss of 0.5%.
      Overall, the soccer players replaced 46% +/- 88% of sweat loss during training,
      and only 4 remained hypohydrated after training. No significant correlations
      between sweat loss and sweat concentrations of Na+ (r = -.11, P = .67) or K+ (r =
      .14, P = .58) were found, but there was a significant correlation with Mg2+ (r = 
      .58, P < .009). This study found large variability in pretraining hydration
      status that the players were able to rehydrate during the training sessions.
      However, given the numbers starting training in a hypohydrated state, adequate
      hydration status before training should be considered by youth players, coaches,
      and sports-science support staff.

PMID- 22645199
TI  - Progression of acromegalic arthropathy despite long-term biochemical control: a
      prospective, radiological study.
AB  - OBJECTIVE: Arthropathy is an invalidating complication of acromegaly, of which
      the prognosis and determinants are currently unknown in treated acromegaly.
      Therefore, the objective of the present study was to investigate the radiographic
      progression of arthropathy over a mean follow-up period of 2.6 years and
      determinants of outcome in patients with long-term, well-controlled acromegaly.
      DESIGN: Prospective follow-up study. METHODS: In a prospective cohort study we
      studied 58 patients (mean age 62, women 41%) with controlled acromegaly for a
      mean of 17.6 years. Radiographic progression of joint disease was defined by the
      Osteoarthritis Research Society International classification as a 1-point
      increase in joint space narrowing (JSN) or osteophyte scores on radiographs of
      the hands, knees, and hips obtained at the first study visit and after 2.6 years.
      Potential risk factors for progression were assessed. RESULTS: Progression of
      osteophytes and JSN was observed in 72 and 74% of patients respectively. Higher
      age predisposed for osteophyte progression. Patients with biochemical control by
      somatostatin (SMS) analogs had more progression of osteophytosis than surgically
      cured patients (odds ratio=18.9, P=0.025), independent of age, sex, BMI, baseline
      IGF1 SDS and exon 3 deletion of the GHR. This was also evident for JSN
      progression, as were higher age and higher baseline IGF1 SDS. CONCLUSIONS:
      Acromegalic patients have progressive JSN and osteophytosis, despite long-term
      biochemical control. Parameters reflecting GH/IGF1 activity were associated with
      progressive joint disease. Remarkably, biochemical control by SMS analogs was
      associated with more progression than surgical cure. Although the present study
      is not a randomized controlled trial, this may indicate insufficient GH control
      according to current criteria and the need for more aggressive therapy.

PMID- 22645200
TI  - Type 2 diabetes from pediatric to geriatric age: analysis of gender and obesity
      among 120,183 patients from the German/Austrian DPV database.
AB  - AIM: To characterize the clinical phenotype of type 2 diabetes mellitus (T2DM)
      with respect to age, gender, and BMI. METHOD: Anonymized data of 120,183 people
      with T2DM from the German/Austrian multicenter Diabetes Patienten
      Verlaufsdokumentation database were analyzed based on chronological age or age at
      diagnosis (0-19, 20-39, 40-59, 60-79, and >=80 years). Age, gender, and BMI
      comparisons with clinical phenotype were made using chi(2) and Kruskal-Wallis
      tests (SAS V9.2). RESULTS: Of all the patients, 51.3% were male, average age was
      67.112.7 years, and average disease duration was 9.99.1 years. More girls than
      boys were diagnosed during adolescence and more men than women during adulthood
      (2060 years). No gender differences existed when age at diagnosis was 60 years.
      Patients were obese on average (BMI: 30.5+/-6.1 kg/m(2)) and had significantly
      higher BMI values than German population peers. The BMI gap was widest in the
      younger age categories and closed with increasing age. Adult women were
      significantly more obese than men. Obese patients more often had elevated HbA1c
      (>=7.5%), hypertension or dyslipidemia (irrespective of age), microalbuminuria
      (adults), or retinopathy (elderly) than nonobese patients. More men than women
      (20-60 years) had hypertension, dyslipidemia, or microalbuminuria while more
      women than men (>=60 years) had hypertension or dyslipidemia. CONCLUSION: During
      puberty, more girls than boys were diagnosed with T2DM while during adulthood
      males predominated. T2DM manifested at comparatively lower BMI in males, and
      younger patients were more obese at diagnosis. Age, gender, and BMI were also
      associated with poor metabolic control and cardiovascular disease
      comorbidities/complications.

PMID- 22645201
TI  - Short-term effects of GH treatment on coagulation, fibrinolysis, inflammation
      biomarkers, and insulin resistance status in prepubertal children with GH
      deficiency.
AB  - OBJECTIVE: The aims of this study was to determine whether prepubertal GH
      deficiency (GHD) children showed any impairment in coagulation- and fibrinolysis
      related parameters and in inflammatory and insulin resistance markers and to
      evaluate the effect of short-term GH therapy on these parameters. DESIGN: This
      was a 6-month, prospective, observational, case-control study (36 prepubertal
      children with GHD and 38 healthy prepubertal children with no differences in
      BMI). Comparison of study parameter values in GHD AND control groups at baseline
      and after 6 months of GH treatment in the GHD group. The following were analyzed:
      glucose, insulin, fibrinogen, absolute plasminogen activator inhibitor type 1
      (aPAI-1), von Willebrand factor (vWF), homeostasis model assessment for insulin
      resistance (HOMA-IR) index, C-reactive protein (CRP), and interleukin 6 (IL6)
      levels. RESULTS: Children with GHD showed higher baseline levels of aPAI-1 and
      fibrinogen and lower levels of glucose, insulin, and HOMA-IR index than healthy
      controls. No intergroup differences were found for vWF. After 6 months of
      treatment, aPAI-1 levels were lower but no changes were observed in fibrinogen or
      vWF levels, which were similar to those of controls. Glucose levels increased,
      though not significantly, while insulin levels and HOMA-IR index rose to normal
      levels. A positive correlation was found between changes in insulin status/HOMA
      IR index and levels of aPAI-1, fibrinogen, vWF, CRP, and IL6. CONCLUSIONS: At
      early ages, GH therapy appears to exert beneficial effects on the amount of aPAI
      1. At the same time, it increases the state of insulin resistance (HOMA-IR index)
      without modifying the levels of fibrinogen, vWF, CRP, and IL6.

PMID- 22645202
TI  - Thyreotropin levels in diabetic patients on metformin treatment.
AB  - OBJECTIVE: A retrospective study to evaluate the changes in TSH concentrations in
      diabetic patients treated or not treated with metformin and/or L-thyroxine (L
      T(4)). METHODS: Three hundred and ninety three euthyroid diabetic patients were
      divided into three groups on the basis of metformin and/or L-T(4) treatment:
      Group (M-/L-), 119 subjects never treated with metformin and L-T(4); Group (M+/L
      ), 203 subjects who started metformin treatment at recruitment; and Group
      (M+/L+), 71 patients on L-T(4) who started metformin recruitment. RESULTS: The
      effect of metformin on serum TSH concentrations was analyzed in relation to the
      basal value of TSH (below 2.5 mIU/L (Q1) or between 2.51 and 4.5 mIU/L (Q2)). In
      patients of group M+/L+, TSH significantly decreased independently from the basal
      level (Q1, from 1.450.53 to 1.011.12 mU/L (P=0.037); Q2, from 3.600.53 to
      1.910.89 mU/L (P<0.0001)). In M+/L group, the decrease in TSH was significant
      only in those patients with a basal high-normal serum TSH (Q2: from 3.24+/-0.51
      to 2.27+/-1.28 mU/l (P=0.004)); in M-/L- patients, no significant changes in TSH
      levels were observed. In patients of group M+/L showing high-normal basal TSH
      levels, a significant decrease in TSH was observed independently from the
      presence or absence of thyroid peroxidase antibodies (ABTPO; Q2 ABTPO +: from
      3.38+/-0.48 to 1.87+/-1.08 mU/l (P<0.001); Q2 AbTPO -: from 3.21+/-0.52 to 2.34+/
      1.31 mU/l (P<0.001)). CONCLUSIONS: These data strengthen the known TSH-lowering
      effect of metformin in diabetic patients on L-T(4) treatment and shows a
      significant reduction of TSH also in euthyroid patients with higher baseline TSH
      levels independently from the presence of AbTPO.

PMID- 22645203
TI  - Myocardium at risk by magnetic resonance imaging: head-to-head comparison of T2
      weighted imaging and contrast-enhanced steady-state free precession.
AB  - AIMS: To determine the myocardial salvage index, the extent of infarction needs
      to be related to the myocardium at risk (MaR). Thus, the ability to assess both
      infarct size and MaR is of central clinical and scientific importance. The aim of
      the present study was to explore the relationship between T2-weighted cardiac
      magnetic resonance (CMR) and contrast-enhanced steady-state free precession (CE
      SSFP) CMR for the determination of MaR in patients with acute myocardial
      infarction. METHODS AND RESULTS: Twenty-one prospectively included patients with
      first-time ST-elevation myocardial infarction underwent CMR 1 week after primary
      percutaneous coronary intervention. For the assessment of MaR, T2-weighted images
      were acquired before and CE-SSFP images were acquired after the injection of a
      gadolinium-based contrast agent. For the assessment of infarct size, late
      gadolinium enhancement images were acquired. The MaR by T2-weighted imaging and
      CE-SSFP was 29 +/- 11 and 32 +/- 12% of the left ventricle, respectively. Thus,
      the MaR with T2-weighted imaging was slightly smaller than that by CE-SSFP (-3.0
      +/- 4.0%; P < 0.01). There was a significant correlation between the two MaR
      measures (r(2)= 0.89, P < 0.01), independent of the time after contrast agent
      administration at which the CE-SSFP was commenced (2-8 min). CONCLUSION: There is
      a good agreement between the MaR assessed by T2-weighted imaging and that
      assessed by CE-SSFP in patients with reperfused acute myocardial infarction 1
      week after the acute event. Thus, both methods can be used to determine MaR and
      myocardial salvage at this point in time.

PMID- 22645204
TI  - Left atrial eccentricity in chronic mitral regurgitation: relation to left atrial
      function.
AB  - AIMS: The aim of this study was to assess the changes in the left atrial (LA)
      shape and to identify the determinants of these changes in chronic mitral
      regurgitation (MR). METHODS AND RESULTS: We enrolled 125 consecutive patients (56
      +/- 16 years, 51% men) with chronic MR caused by myxomatous mitral valve disease
      in sinus rhythm and 45 control patients (54 +/- 15 years, 55% men) undergoing
      transthoracic Doppler echocardiography. The LA eccentricity index (LAEi) and the
      LA volume index (LAVi) were used to estimate the LA shape and size, respectively.
      There were significant decreases in LAEi (r= -0.723, P< 0.001) and increases in
      LAVi (r= 0.642, P< 0.001) with increasing severity of MR. In multivariate
      stepwise linear regression analysis, regurgitant fraction (RF) was an independent
      determinant of the LAE, whereas RF, left ventricular (LV) mass index and LV
      diastolic dysfunction grade were independent determinants of the LA volume. The
      LAEi was positively related to the velocity of A' in the entire population (r =
      0.238, P = 0.002). On the receiver operating characteristic (ROC) curve analysis,
      LAEi <=1.30 was the best cut-off value to reflect the LA systolic dysfunction (A'
      velocity <7 cm/s; area under the curve was 0.78, P < 0.001). CONCLUSION: LA
      becomes more spherical with increasing severity of MR, suggesting a decrease in
      LAE, which is mainly determined by the volume overload. LAE might be closely
      related to the LA systolic function in chronic MR.

PMID- 22645205
TI  - Intra-myocardial left ventricular lipoma associated with non-compaction
      cardiomyopathy.

PMID- 22645206
TI  - Assessment of subclinical atherosclerosis using contrast-enhanced ultrasound.
AB  - AIMS: The sensitivity of standard carotid ultrasound and colour Doppler for the
      detection of subclinical atherosclerotic plaques is suboptimal. The aim of this
      study is to assess whether contrast-enhanced ultrasound (CEUS) added to standard
      carotid ultrasound improves the detection of subclinical atherosclerosis. METHODS
      AND RESULTS: Carotid intima-media thickness (CIMT) measurement, standard carotid
      ultrasound including colour Doppler imaging, and CEUS were performed in 100
      asymptomatic patients with one or more risk factors for atherosclerosis. CEUS was
      performed using intravenous administration of SonoVueTM contrast agent (Bracco
      S.p.A., Milan, Italy). CIMT, standard ultrasound, colour Doppler, and CEUS were
      reviewed by two independent observers. Standard ultrasound, colour Doppler, and
      CEUS were scored for the presence of atherosclerotic plaques. Subclinical
      atherosclerosis was diagnosed if patients had a CIMT above their age-corrected
      threshold value or if atherosclerotic plaques were present on standard carotid
      ultrasound clips or CEUS clips. McNemar's test was performed to compare between
      groups. Twenty-one patients (21%) had a thickened CIMT value and were considered
      to have subclinical atherosclerosis. Standard carotid ultrasound including colour
      Doppler demonstrated atherosclerotic plaques in 77 patients (77%). The addition
      of CEUS to the standard ultrasound protocol demonstrated atherosclerotic plaques
      in 88 patients (88%). The incorporation of CEUS into the standard carotid
      ultrasound protocol resulted in a significantly improved detection of patients
      with subclinical atherosclerosis (P < 0.01). CONCLUSION: CEUS has an incremental
      value for the detection of subclinical atherosclerosis in the carotid arteries.
      Atherosclerotic plaques which were only detected with CEUS and not with standard
      carotid ultrasound and colour Doppler imaging were predominantly hypoechoic.

PMID- 22645207
TI  - Ventilator associated pneumonia.

PMID- 22645208
TI  - Relation between volume and outcome for patients with severe sepsis in United
      Kingdom: retrospective cohort study.
AB  - OBJECTIVE: To evaluate whether a relation exists between volume and outcome for
      admissions with severe sepsis to adult general critical care units in the United
      Kingdom. DESIGN: Retrospective cohort study using data from a pooled case mix and
      outcome database. SETTING: Adult general critical care units participating in the
      case mix programme. PARTICIPANTS: Consecutive admissions to participating units
      for the years 2008-09 meeting objective, standardised criteria for severe sepsis.
      MAIN OUTCOME MEASURES: Mortality at ultimate discharge from acute hospital.
      RESULTS: The primary exposure was volume of admissions with severe sepsis per
      unit per year. A multivariable logistic regression analysis, using generalised
      estimating equations, was used to assess the association between volume, modelled
      using fractional polynomials, and ultimate acute hospital mortality while
      adjusting for potential confounders. No relation was seen between volume and
      outcome for admissions with severe sepsis to adult, general critical care units
      in the UK. Subgroup analyses tested for interactions between the effect of volume
      and acute severity of illness or receipt of mechanical ventilation. No
      significant interactions were found. CONCLUSIONS: This study showed no relation
      between volume and outcome in admissions with severe sepsis treated in adult
      general critical care units in the UK.

PMID- 22645209
TI  - Severe sepsis in the UK and the case volume-outcome association.

PMID- 22645210
TI  - Gitelman syndrome.

PMID- 22645211
TI  - A doctor's lifelong campaign to revive the Olympic games.

PMID- 22645213
TI  - Safer sport, shock treatment, stroke care, and safety triumph at the BMJ Group
      awards.

PMID- 22645214
TI  - What's wrong with assisted dying.

PMID- 22645215
TI  - That joke isn't funny any more.

PMID- 22645216
TI  - What lies beneath: an unusual case of tuberculous osteomyelitis.

PMID- 22645217
TI  - Characteristics of patients transported by an air ambulance critical care team.
AB  - BACKGROUND: The aim of this study was to review patients conveyed by the Great
      Western Air Ambulance to its main receiving hospital. METHODS: Retrospective data
      were collected for all patients transferred to Frenchay Hospital by the Great
      Western Air Ambulance between 1 June 2008 and 1 March 2010. RESULTS: 115 patients
      were included in the review. Patients were conveyed up to 85 km, 79% bypassing
      the closest emergency department (ED). 51% of these patients had major trauma and
      35% were intubated at the scene. On arrival, the mean time to CT scan was 78 min,
      reduced to 63 min for those with a head injury. 16% of patients were discharged
      from the ED. CONCLUSIONS: This review provides an overview of the characteristics
      of patients transferred to a major receiving hospital by a prehospital critical
      care team.

PMID- 22645218
TI  - Diagnostic performance of procalcitonin for hospitalised children with acute
      pyelonephritis presenting to the paediatric emergency department.
AB  - OBJECTIVES: Urinary tract infection (UTI) is a common bacterial infection in
      children that can result in permanent renal damage. This study prospectively
      assessed the diagnostic performance of procalcitonin (PCT) for predicting acute
      pyelonephritis (APN) among children with febrile UTI presenting to the paediatric
      emergency department (ED). METHODS: Children aged <=10 years with febrile UTI
      admitted to hospital from the paediatric ED were prospectively studied. Blood
      PCT, C reactive protein (CRP) and white blood cell (WBC) count were measured in
      the ED. Sensitivity, specificity, predictive values, multilevel likelihood
      ratios, receiver operating characteristic (ROC) curve analysis and multivariate
      logistic regression were used to assess quantitative variables for diagnosing
      APN. RESULTS: The 136 enrolled patients (56 boys and 80 girls; age range 1 month
      to 10 years) were divided into APN (n=87) and lower UTI (n=49) groups according
      to (99m)Tc-dimercaptosuccinic acid scan results. The cut-off value for maximum
      diagnostic performance of PCT was 1.3 ng/ml (sensitivity 86.2%, specificity
      89.8%). By multivariate regression analysis, only PCT and CRP were retained as
      significant predictors of APN. Comparing ROC curves, PCT had a significantly
      greater area under the curve than CRP, WBC count and fever for differentiating
      between APN and lower UTI. CONCLUSIONS: PCT has better sensitivity and
      specificity than CRP and WBC count for distinguishing between APN and lower UTI.
      PCT is a valuable marker for predicting APN in children with febrile UTI. It may
      be considered in the initial investigation and therapeutic strategies for
      children presenting to the ED.

PMID- 22645219
TI  - Commission calls for city planners to consider health issues.

PMID- 22645220
TI  - Factors associated with inconsistent sun protection in first-degree relatives of
      melanoma survivors.
AB  - First-degree relatives (FDRs) of melanoma survivors are at heightened risk for
      developing melanoma, but use sun protection inconsistently. To develop
      appropriate interventions, in this article we identify factors related to sun
      protection inconsistency in melanoma FDRs using ethnographic decision tree
      modeling. We conducted in-home interviews with 25 melanoma FDRs balanced across
      gender and sunbathing attitudes and identified factors related to daily decision
      making about use of sunscreen, shade seeking, hats, and clothing. Results
      indicated primary facilitators for sun protection involved water settings and
      sunny weather. Physical activities such as exercise served to promote as well as
      inhibit sun protection. If participants anticipated shade cover, they tended to
      forgo other sun protection. The use of hats and clothing was often dictated by
      nonsun-protection goals. Understanding factors related to inconsistent sun
      protection with detail and nuance is an important prerequisite to interventions
      aimed to improve sun-protection maintenance in this population.

PMID- 22645221
TI  - Inner contradictions among men who bareback.
AB  - Barebacking, or intentional unprotected anal intercourse when HIV transmission
      can occur, emerged as a descriptive term in the 1990s, and marked greater
      acceptance by gay and bisexual men of dispensing with condom use under certain
      circumstances. In an exploratory study of men who used Internet sites to meet
      partners and reported recent episodes of barebacking, respondents outlined
      numerous strategies they deployed to avoid HIV infection instead of universal
      condom use. However, in interviews many participants acknowledged uneasiness with
      the flaws in their chosen strategies, and the contradiction between their urgent
      desire to remain HIV-free and their sexual practices. For some, the dissonance
      between the conflicting cognitions could be resolved through self-justification,
      mental compartmentalization, or invincibility beliefs so that barebacking could
      continue. For this subpopulation, continued reiteration of cognitive-based
      prevention messages has the potential to reinforce rather than undermine their
      attachment to inadequate strategies for disease avoidance.

PMID- 22645222
TI  - Caring for a parent with lung cancer: caregivers' perspectives on the role of
      communication.
AB  - We investigated communication and care in the context of lung cancer through
      qualitative interviews with 35 adult children. Participants described two core
      influences on communication: situational and relational influences. Participants
      also suggested that the ways in which support was communicated impacted how they
      managed challenges and how they were able to cope with the loss of their parent.
      This research adds to the literature on caregiving and communicating social
      support by exploring the experiences of families coping with lung cancer. We
      suggest theoretical and practical implications for the ways family members might
      communicate about illness.

PMID- 22645223
TI  - Body perceptions and health behaviors in an online bodybuilding community.
AB  - In this article we explore the social constructions, body perceptions, and health
      experiences of a serious recreational and competitive bodybuilder and powerlifter
      community. Data were obtained from a discussion forum appearing within an online
      community dedicated to muscular development. Forum postings for a period of 36
      months were transposed to QSR NVivo, in which a narrative-based analytical method
      employing Gee's coding approach was employed. We used a priori codes based on
      Bourdieu's multipronged conceptual categories of social field, habitus, and
      capital accumulation as a theoretical frame. Our results expose an extreme social
      reality held by a devoted muscle-building community with a fanatical obsession
      with muscular hypertrophy and any accouterment helpful in its acquisition, from
      nutrition and supplements to training regimes and anabolic androgenic substances.
      Few health costs were considered too severe in this muscular meritocracy, where
      the strong commanded deference and the massive dominated the social field.

PMID- 22645224
TI  - Using first nations children's perceptions of food and activity to inform an
      obesity prevention strategy.
AB  - Obesity and associated health risks disproportionately affect Aboriginal (First
      Nations) children in Canada. The purpose of this research study was to elicit
      First Nations children's perceptions of food, activity, and health to inform a
      community-based obesity prevention strategy. Fifteen 4th- and 5th-Grade students
      participated in one of three focus group interviews that utilized drawing and
      pile-sorting activities. We used an ecological lens to structure our findings.
      Analyses revealed that a variety of interdependent sociocultural factors
      influenced children's perceptions. Embedded within a cultural/traditional
      worldview, children indicated a preference for foods and activities from both
      contemporary Western and traditional cultures, highlighted family members as
      their main sources of health information, and described information gaps in their
      health education. Informed by children's perspectives, these findings offer
      guidance for developing an obesity prevention strategy for First Nations children
      in this community.

PMID- 22645226
TI  - "It's like we're grasping at anything": caregivers' education needs and preferred
      learning methods.
AB  - In this qualitative descriptive study, we explored caregivers' educational needs
      and preferred methods of information delivery. Descriptions are based on five
      focus groups (N = 29) conducted with ethnically diverse, current and past family
      caregivers, including those who had previously attended a structured educational
      program. Themes arose from verbatim data transcriptions and coded themes. Four
      categories of educational needs were identified: (a) respite, (b) caregiving
      essentials, (c) self-care, and (d) the emotional aspects of caregiving.
      Advantages and disadvantages of learning methods are discussed, along with
      reasons for and outcomes of attending caregiver workshops. An informed caregiver
      model is proposed. Health care providers must assess educational needs and strive
      to provide appropriate information as dictated by the care recipient's condition
      and caregiver's expressed desires. Innovative methods of delivering information
      that are congruent with different caregiving circumstances and learning
      preferences must be developed and tested.

PMID- 22645225
TI  - African American and non-African American patients' and families' decision making
      about renal replacement therapies.
AB  - We conducted focus group meetings of African American and non-African American
      patients with end-stage renal disease (six groups) and their family members (six
      groups), stratified by race/ethnicity and treatment. We elicited differences in
      participants' experiences with shared decision making about initiating renal
      replacement therapy (RRT; that is, hemodialysis, peritoneal dialysis, or a kidney
      transplant). Patients were often very sick when initiating RRT, and had little,
      if any, time to make a decision about what type of RRT to initiate. They also
      lacked sufficient information about alternative treatment options prior to
      initiation. Family members played supportive roles and shared in decision making
      when possible. Reports were similar for African American and non-African American
      participants. Our findings suggest that a greater emphasis on the improved
      engagement of patients and their families in shared decision making about RRT
      initiation is needed for both ethnic/racial minorities and nonminorities.

PMID- 22645227
TI  - Neuroendocrine tumor disease: an evolving landscape.
AB  - Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a
      heterogenous group of tumors arising from a variety of neuroendocrine cell types.
      The incidence and prevalence of GEP-NENs have markedly increased over the last
      three decades. Symptoms are often absent in early disease, or vague and
      nonspecific even in advanced disease. Delayed diagnosis is thus common.
      Chromogranin A is the most commonly used biomarker but has limitations as does
      the proliferative marker Ki-67%, which is often used for tumor grading and
      determination of therapy. The development of a multidimensional prognostic
      nomogram may be valuable in predicting tumor behavior and guiding therapy but
      requires validation. Identification of NENs that express somatostatin receptors
      (SSTR) allows for SSTR scintigraphy and positron emission tomography imaging
      using novel radiolabeled compounds. Complete surgical resection of limited
      disease or endoscopic ablation of small lesions localized in stomach or rectum
      can provide cure; however, the majority of GEP-NENs are metastatic (most
      frequently the liver and/or mesenteric lymph nodes) at diagnosis. Selected
      patients with metastatic disease may benefit from advanced surgical techniques
      including hepatic resection or liver transplantation. Somatostatin analogs are
      effective for symptomatic treatment and exhibit some degree of antiproliferative
      activity in small intestinal NENs. There is a place for streptozotocin,
      temozolomide, and capecitabine in the management of pancreatic NENs, while new
      agents targeting either mTOR (everolimus) or angiogenic (sunitinib) pathways have
      shown efficacy in these lesions.

PMID- 22645228
TI  - Expression of guanylyl cyclase-B (GC-B/NPR2) receptors in normal human fetal
      pituitaries and human pituitary adenomas implicates a role for C-type natriuretic
      peptide.
AB  - C-type natriuretic peptide (CNP/Nppc) is expressed at high levels in the anterior
      pituitary of rats and mice and activates guanylyl cyclase B receptors (GC-B/Npr2)
      to regulate hormone secretion. Mutations in NPR2/Npr2 can cause achondroplasia,
      GH deficiency, and female infertility, yet the normal expression profile within
      the anterior pituitary remains to be established in humans. The current study
      examined the expression profile and transcriptional regulation of NPR2 and GC-B
      protein in normal human fetal pituitaries, normal adult pituitaries, and human
      pituitary adenomas using RT-PCR and immunohistochemistry. Transcriptional
      regulation of human NPR2 promoter constructs was characterized in anterior
      pituitary cell lines of gonadotroph, somatolactotroph, and corticotroph origin.
      NPR2 was detected in all human fetal and adult pituitary samples regardless of
      age or sex, as well as in all adenoma samples examined regardless of tumor
      origin. GC-B immunoreactivity was variable in normal pituitary,
      gonadotrophinomas, and somatotrophinomas. Maximal transcriptional regulation of
      the NPR2 promoter mapped to a region within -214 bp upstream of the start site in
      all anterior pituitary cell lines examined. Electrophoretic mobility shift assays
      revealed that this region contains Sp1/Sp3 response elements. These data are the
      first to show NPR2 expression in normal human fetal and adult pituitaries and
      adenomatous pituitary tissue and suggest a role for these receptors in both
      pituitary development and oncogenesis, introducing a new target to manipulate
      these processes in pituitary adenomas.

PMID- 22645229
TI  - Offenders' attachment and sexual abuse onset: a test of theoretical propositions.
AB  - Confidential self-report data obtained on 107 adult male child sexual abusers
      were analyzed to test theoretical propositions concerning the role of attachment
      problems in the onset of sexual offending. Offenders' parent-child attachment
      relationships were most frequently characterized by affectionless control,
      reflecting low parental care and high overprotection and control. Offenders
      reported significantly less secure attachment with their fathers than with their
      mothers. Overall, weak continuity from childhood attachment to trait (general)
      adult attachment was found, with insecure attachment more stable than secure
      attachment. Childhood attachment problems, particularly with fathers, were more
      clearly reflected in state adult attachment (i.e., in the month preceding sexual
      offending onset) than in trait adult attachment. Offenders who were in an adult
      intimate relationship prior to their onset sexual offense reported significant
      state increases in attachment avoidance, and their onset offenses were more
      likely to involve a female familial victim. Offenders who were not in a
      relationship prior to offending onset were younger, and their onset sexual
      offenses occurred in much more diverse circumstances. These findings provide
      tentative evidence that directly and indirectly implicates offenders' attachment
      problems specifically in the onset of their sexual abuse behavior. Implications
      for developmental prevention and early intervention, situational prevention, and
      offender treatment are discussed.

PMID- 22645230
TI  - Predicting reoffense for community-based sexual offenders: an analysis of 30
      years of data.
AB  - This study contributes to the area of risk prediction by exploring whether the
      Static-99R is useful for predicting reoffense in community-based samples, and for
      noncontact offenders with and without identified victims. A total of 744
      participants drawn from an outpatient sex offender treatment program in a large
      metropolitan area were followed for a period of up to 30 years. Multiple Cox
      Regressions were run; covariates included length of treatment, status in
      treatment, Static-99R items, and number of technical probation violations.
      Overall, reoffending was an infrequent occurrence in this sample regardless of
      how it was defined, with sexual reoffenses identified in 13% of the sample and
      any criminal reoffense identified in 20% of the sample. Consistent with previous
      research, the Static-99R was a better predictor of sex-related reoffenses than of
      nonsexual reoffenses. However, in no case were more than a couple of the items
      significantly related to reoffending and these items differed depending on
      reoffense definition.

PMID- 22645232
TI  - Draft genome sequence of the yeast Pachysolen tannophilus CBS 4044/NRRL Y-2460.
AB  - A draft genome sequence of the yeast Pachysolen tannophilus CBS 4044/NRRL Y-2460
      is presented. The organism has the potential to be developed as a cell factory
      for biorefineries due to its ability to utilize waste feedstocks. The sequenced
      genome size was 12,238,196 bp, consisting of 34 scaffolds. A total of 4,463 genes
      from 5,346 predicted open reading frames were annotated with function.

PMID- 22645233
TI  - Genome sequence of an unclassified pleosporales species isolated from human
      nasopharyngeal aspirate.
AB  - Pleosporales is the largest order in the fungal class Dothideomycetes. We report
      the 36,814,818-bp draft genome sequence and gene annotation of UM1110, a
      Pleosporales isolate associated with unclassified genera that is potentially a
      new fungal species. Analysis of the genome sequence led to the finding of genes
      associated with fungal adhesive proteins, secreted proteases, allergens, and
      pseudohyphal development.

PMID- 22645235
TI  - Unusual use of a tip-versatile ablation catheter in the ablation of peri-nodal
      atrial tachycardia.

PMID- 22645234
TI  - High-degree atrioventricular block complicating ST-segment elevation myocardial
      infarction in the era of primary percutaneous coronary intervention.
AB  - AIMS: Primary percutaneous coronary intervention (pPCI) has replaced thrombolysis
      as treatment-of-choice for ST-segment elevation myocardial infarction (STEMI).
      However, the incidence and prognostic significance of high-degree
      atrioventricular block (HAVB) in STEMI patients in the pPCI era has been only
      sparsely investigated. The objective of this study was to assess the incidence,
      predictors and prognostic significance of HAVB in STEMI patients treated with
      pPCI. METHODS AND RESULTS: This study included 2073 STEMI patients treated with
      pPCI. The patients were identified through a hospital register and the Danish
      National Patient Register. Both registers were also used to establish the
      diagnosis of HAVB. All-cause mortality was the primary endpoint. During a median
      follow-up of 2.9 years [interquartile range (IQR) 1.8-4.0] 266 patients died.
      High-degree atrioventricular block was documented in 67 (3.2%) patients of whom
      25 died. Significant independent predictors of HAVB included right coronary
      artery occlusion, age >65 years, female gender, hypertension, and diabetes. The
      adjusted mortality rate was significantly increased in patients with HAVB
      compared to patients without HAVB [hazard ratio = 3.14 (95% confidence interval
      2.04-4.84), P< 0.001]. A landmark-analysis 30 days post-STEMI showed equal
      mortality rates in the two groups. CONCLUSION: The incidence of HAVB in STEMI
      patients treated with pPCI has been reduced compared with reports from the
      thrombolytic era. However, despite this improvement high-degree AV block remains
      a severe prognostic marker in the pPCI era. The mortality rate was only increased
      within the first 30 days. High-degree atrioventricular block patients who
      survived beyond this time-point thus had a prognosis equal to patients without
      HAVB.

PMID- 22645236
TI  - The relationship between avoidable hospitalization and accessibility to primary
      care: a systematic review.
AB  - BACKGROUND: Avoidable hospitalization (AH) has been widely studied as a possible
      measure of the performance of primary health care (PHC). However, studies
      examining the relationship between the efficiency and quality of PHC and AH have
      found mixed results. Our study aims at highlighting those factors related to the
      relationship between AH and accessibility to PHC in different countries. METHODS:
      We conducted a systematic search for peer-reviewed studies published between 1990
      and October 2010 in English, German, French, Italian or Spanish and indexed
      primary electronic databases. RESULTS: The final analysis was conducted on the
      basis of 51 papers. Of them, 72.5% revealed a significant inverse association
      between the indicator of PHC accessibility and rates of AH. Indicators of PHC
      calculated at individual level are more likely to reveal contradictory aspects of
      the relationship between rates of AH and indicators of quality and PHC
      accessibility. CONCLUSIONS: Most studies confirmed the expected relationship
      between indicators of PHC accessibility and hospitalization for ambulatory care
      sensitive conditions (ACSCs), showing lower hospitalization rates for ACSC in
      areas with greater access to PHC. The findings support the use of ACSC
      hospitalization as an indicator of primary care quality, with the precaution of
      applying appropriate adjustment factors.

PMID- 22645237
TI  - Exposure to paracetamol and asthma symptoms.
AB  - BACKGROUND: Paracetamol is one of the factors that have been associated with the
      observed increase in asthma prevalence in the last few years. The influence of
      environmental or genetic factors in this disease may be different in some
      countries than in others. The purpose of this study was to analyse the
      relationship between the paracetamol consumption and asthma prevalence in our
      community. METHODS: A cross-sectional study was conducted on more than 20,000
      children and adolescents in Galicia, Spain. The International Study of Asthma and
      Allergies in Childhood methodology was used to collect the information on asthma
      symptoms in children, paracetamol consumption, body mass index (BMI), pets in the
      home, education level of the mother and parental asthma and smoking habits. The
      influence of paracetamol consumption on the prevalence of asthma symptoms was
      calculated using logistic regression, adjusted for the other parameters included
      in the study. RESULTS: After adjusting for gender, BMI, having a cat or dog,
      maternal education, parental asthma and smoking, in 6- to 7-year-old children,
      the consumption of paracetamol during the first year of life is associated with
      asthma [odds ratio (OR) 2.04 (1.79-2.31) for wheezing at some time]. Paracetamol
      consumption in the previous year leads to a significant increase in the
      probability of wheezing at some time [OR 3.32 (2.51-4.41)] in young children and
      adolescents [OR 2.12 (1.68-2.67)]. CONCLUSIONS: Paracetamol consumption is
      associated with a significant increase in asthma symptoms. The effect is greater
      the more often the drug is taken.

PMID- 22645238
TI  - Small-area analysis of social inequalities in residential exposure to road
      traffic noise in Marseilles, France.
AB  - BACKGROUND: Few studies have focused on the social inequalities associated with
      environmental noise despite its significant potential health effects. This study
      analysed the associations between area socio-economic status (SES) and potential
      residential exposure to road traffic noise at a small-area level in Marseilles,
      second largest city in France. METHODS: We calculated two potential road noise
      exposure indicators (PNEI) at the census block level (for 24-h and night
      periods), with the noise propagation prediction model CadnaA. We built a
      deprivation index from census data to estimate SES at the census block level.
      Locally estimated scatterplot smoothing diagrams described the associations
      between this index and PNEIs. Since the extent to which coefficient values vary
      between standard regression models and spatial methods are sensitive to the
      specific spatial model, we analysed these associations further with various
      regression models controlling for spatial autocorrelation and conducted
      sensitivity analyses with different spatial weight matrices. RESULTS: We observed
      a non-linear relation between the PNEIs and the deprivation index: exposure
      levels were highest in the intermediate categories. All the spatial models led to
      a better fit and more or less pronounced reductions of the regression
      coefficients; the shape of the relations nonetheless remained the same.
      CONCLUSION: Finding the highest noise exposure in midlevel deprivation areas was
      unexpected, given the general literature on environmental inequalities. It
      highlights the need to study the diversity of the patterns of environmental
      inequalities across various economic, social and cultural contexts. Comparative
      studies of environmental inequalities are needed, between regions and countries,
      for noise and other pollutants.

PMID- 22645239
TI  - Micro- and meso-level influences on obesity in the former Soviet Union: a multi
      level analysis.
AB  - BACKGROUND: Limited evidence exists on obesity in the former Soviet Union (fSU),
      particularly its micro- and meso-level determinants. The objectives of this study
      were to determine age- and gender-adjusted prevalence of self-reported overweight
      and obesity in nine fSU countries; explore the relationship between individual
      and household (micro-level) factors and obesity; and explore the relationship
      between features of nutritional and physical environments (meso-level) and
      obesity. METHODS: Data were collected from 18,000 adults using household surveys
      and from 333 communities using community profiles in Azerbaijan, Armenia,
      Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia and Ukraine in 2010.
      Individual- and community-level determinants of self-reported obesity (body mass
      index >= 30 kg/m(2)) were analysed using multi-level random intercept logistic
      regression models. RESULTS: A total of 13% of the males and 18% of the females
      were categorized as obese. Factors associated with obesity in males were older
      age, increasing educational achievement, declining self-reported health, alcohol
      consumption and automobile ownership. Males who were current smokers, not married
      and perceived physical activity to be important were less likely to be obese. For
      females, obesity was associated with older age, completion of secondary-level
      education, declining self-reported health and average household financial
      situation. Unmarried women were less likely to be obese. Multi-level analysis
      indicated that individuals living in communities with higher presence of garbage
      were more likely to be obese. CONCLUSIONS: This is the first study to examine
      both micro- and meso-level influences on obesity in fSU using multi-level
      analysis. Findings indicate a similar obesity risk profile to countries in
      Western Europe and North America.

PMID- 22645240
TI  - Lifecourse SEP and tobacco and cannabis use.
AB  - BACKGROUND: Social inequalities in substance use have been well-documented;
      however, the impact of changes in socio-economic position from childhood to
      adulthood is unclear. We examined the relationship between intergenerational
      trajectories of social position and tobacco and cannabis use among young adults.
      METHODS: Data come from 1103 participants (mean age: 28.9 years) of the
      Trajectoires Epidemiologiques en Population (TEMPO) study and their parents,
      participants of the GAZEL study, France. Multinomial regression analyses were
      used to examine associations between lifecourse socio-economic position (SEP)
      assessed using the parent's reports of family income (1989 and 2002) and the
      participant's educational attainment, occupational grade and job stability in
      2009, with self-reported tobacco and cannabis use in 2009. RESULTS: Compared with
      participants with stable intermediate/high SEP, those with stable low SEP and
      those with declining SEP were more likely to use tobacco (age- and sex-adjusted
      ORs = 2.03 and 2.26). Participants who experienced declining SEP were also
      disproportionately likely to use and abuse cannabis (adjusted ORs = 2.22 and
      2.73). Associations remained significant after adjusting for family (parental
      smoking, alcohol use, ill health, unemployment, depression and divorce) and
      individual (early tobacco and cannabis use, academic difficulties, juvenile
      internalizing and externalizing problems) risk factors. CONCLUSIONS: Cross
      sectional studies indicate social inequalities in substance use. Our longitudinal
      findings suggest that individuals who experienced declining SEP from childhood to
      adulthood may be twice as likely to use tobacco and cannabis compared with
      individuals with a stable/high trajectory. Interventions targeting substance
      abuse should take into account lifecourse determinants including the interplay
      between individuals' socio-economic origins and later attainment.

PMID- 22645241
TI  - Longitudinal relation between weight change and quality of life in a community
      based population: a prospective cohort study.
AB  - BACKGROUND: Previous cross-sectional studies revealed that obesity is associated
      with lower health-related quality of life (HRQOL). This study aimed to
      investigate the longitudinal association between 5-year weight change and HRQOL.
      METHODS: Data from 2414 Dutch men and women was collected. HRQOL was measured
      with the RAND-36. Weight change was calculated as change in weight between 1998
      and 2003. Using generalized estimation equations, we primarily analyzed the
      influence of weight change on HRQOL for the total population and additionally, by
      change groups (weight losers, weight maintainers and weight gainers) using
      regression analysis. All analyses were stratified for gender. RESULTS: After 5
      years, 598 men (50%) and 646 women (54%) maintained their weight, 177 men (15%)
      and 163 women (14%) lost >2.5 kg and 410 men (35%) and 379 women (32%) gained
      >2.5 kg. Longitudinal associations of 5-year weight change and HRQOL were found
      for mental component score (MCS) in women (beta = 0.13; 95% CI: 0.02-0.24), and
      physical component score (PCS) in men (beta = -0.09; 95% CI: -0.17 to -0.00) and
      women (beta = -0.10; 95% CI: -0.19 to -0.01). Categorizing for 5-year weight
      change showed that weight gainers and weight losers did not significantly differ
      from weight maintainers on both MCS and PCS for both men and women. CONCLUSION:
      Weight change over 5 years leaded to a slight, though significant reduction on
      the PCS in both genders. In women, we found a positive association between weight
      change and MCS.

PMID- 22645242
TI  - A case of recurrent lacrimal gland tumor treated by orbital exenteration.

PMID- 22645243
TI  - Mortality attributable to tobacco by selected countries based on the WHO Global
      Report.

PMID- 22645244
TI  - miR-107: a toll-like receptor-regulated miRNA dysregulated in obesity and type II
      diabetes.
AB  - miRNAs are small noncoding RNAs that act as regulators of gene expression.
      Dysregulation of miRNAs has been shown to contribute to multiple disease
      processes. It has become apparent that miRNAs play a key role in the innate
      immune response, whereby a large number of miRNAs have been demonstrated to be
      regulated by TLRs, key initiators of the innate immune response to infection.
      Recently, the LPS receptor, TLR4, has been shown to down-regulate miR-107 in
      macrophages. In addition, miR-107 has been demonstrated to be dysregulated in
      murine and rodent models of obesity and insulin resistance, respectively, with
      miR-107 contributing to both conditions. With obesity and inflammation being so
      intrinsically associated, the link between the miR-107 expression levels,
      inflammation, and insulin resistance may be of particular importance in metabolic
      diseases. The decrease in miR-107 in response to TLR4 may be an attempt to limit
      insulin resistance, a feature of obesity-related inflammation. If this process is
      impaired, disease, such as T2D, might persist. This review aims to discuss a
      possible link between the molecular phenomena of obesity and inflammation and the
      role that miR-107 may contribute to these processes.

PMID- 22645245
TI  - Annexin A2 is critical for embryo adhesiveness to the human endometrium by RhoA
      activation through F-actin regulation.
AB  - Annexin A2 (ANXA2) is present in vivo in the mid- and late-secretory endometria
      and is mainly localized in the luminal epithelium. Our aim was to evaluate its
      function in regulating the human implantation process. With an in vitro adhesion
      model, constructed to evaluate how the mouse embryo and JEG-3 spheroids attach to
      human endometrial epithelial cells, we demonstrated that ANXA2 inhibition
      significantly diminishes embryo adhesiveness. ANXA2 is also implicated in
      endometrial epithelial cell migration and trophoblast outgrowth. ANXA2 was seen
      to be linked to the RhoA/ROCK pathway and to regulate cell adhesion. We noted
      that ANXA2 inhibition significantly reduces active RhoA, although RhoA
      inactivation does not alter the ANXA2 levels. RhoA inactivation and ROCK
      inhibition also moderate embryo adhesiveness to endometrial epithelial cells. We
      corroborated that the induction of constitutively active RhoA partially reverses
      the effects of ANXA2 inhibition on endometrial adhesiveness. These molecules
      colocalize on the plasma membrane of endometrial epithelial cells, and a large
      proportion of ANXA2 and RhoA are colocalized in the F-actin networks. The
      functional effects of ANXA2 inhibition and RhoA/ROCK inactivation are associated
      with significant alterations in F-actin organization and its depolymerization.
      ANXA2 may act upstream of the RhoA/ROCK pathway by regulating F-actin remodeling
      and is a key factor in human endometrial adhesiveness.

PMID- 22645246
TI  - Prostaglandin E2 increases fibroblast gene-specific and global DNA methylation
      via increased DNA methyltransferase expression.
AB  - Although alterations in DNA methylation patterns have been associated with
      specific diseases and environmental exposures, the mediators and signaling
      pathways that direct these changes remain understudied. The bioactive lipid
      mediator prostaglandin E(2) (PGE(2)) has been shown to exert a myriad of effects
      on cell survival, proliferation, and differentiation. Here, we report that PGE(2)
      also signals to increase global DNA methylation and DNA methylation machinery in
      fibroblasts. HumanMethylation27 BeadChip array analysis of primary fetal (IMR-90)
      and adult lung fibroblasts identified multiple genes that were hypermethylated in
      response to PGE(2). PGE(2), compared with nontreated controls, increased
      expression and activity (EC(50)~10(7) M) of one specific isoform of DNA
      methyltransferase, DNMT3a. Silencing of DNMT3a negated the ability of PGE(2) to
      increase DNMT activity. The increase in DNMT3a expression was mediated by PGE(2)
      signaling via its E prostanoid 2 receptor and the second messenger cAMP. PGE(2),
      compared with the untreated control, increased the expression and activity of Sp1
      and Sp3 (EC(50)~3*10(7) M), transcription factors known to increase DNMT3a
      expression, and inhibition of these transcription factors abrogated the PGE(2)
      increase of DNMT3a expression. These findings were specific to fibroblasts, as
      PGE(2) decreased DNMT1 and DNMT3a expression in RAW macrophages. Taken together,
      these findings establish that DNA methylation is regulated by a ubiquitous
      bioactive endogenous mediator. Given that PGE(2) biosynthesis is modulated by
      environmental toxins, various disease states, and commonly used pharmacological
      agents, these findings uncover a novel mechanism by which alterations in DNA
      methylation patterns may arise in association with disease and certain
      environmental exposures.

PMID- 22645247
TI  - The novel structure of a cytosolic M14 metallocarboxypeptidase (CCP) from
      Pseudomonas aeruginosa: a model for mammalian CCPs.
AB  - PaCCP is a metallocarboxypeptidase (MCP) of the M14 family from Pseudomonas
      aeruginosa, which belongs to a bacterial clade of carboxypeptidases that are
      homologous to the recently discovered M14D subfamily of human nonsecretory
      cytosolic carboxypeptidases (CCPs). CCPs are intracellular peptidases involved,
      among other roles, in the post-translational modifications of tubulin. Here we
      report the crystal structure of PaCCP at high resolution (1.6 A). Its 375
      residues are folded in a novel beta-sandwich N-terminal domain followed by the
      classical carboxypeptidase alpha/beta-hydrolase domain, this one in a shorter and
      more compact form. The former is unique in the whole family and does not have
      sequential or structural homology with other domains that are usually flanking
      the latter, like the prodomain of the M14A subfamily or the C-terminal
      transthyretin/prealbumin-like domains of the M14B subfamily. PaCCP does not
      display activity against small carboxypeptidase substrates, so in this form it
      might constitute an inactive precursor of the protease. Structural results
      derived from cocrystallization with well-known inhibitors of MCPs indicate that
      the enzyme might only possess C-terminal hydrolase activity against cellular
      substrates of particular specificity and/or when undergoes structural
      rearrangements. The derived PaCCP structure allows a first structural insight
      into the more complex and largely unknown mammalian CCP subfamily.

PMID- 22645248
TI  - The BUME method: a novel automated chloroform-free 96-well total lipid extraction
      method for blood plasma.
AB  - Lipid extraction from biological samples is a critical and often tedious
      preanalytical step in lipid research. Primarily on the basis of automation
      criteria, we have developed the BUME method, a novel chloroform-free total lipid
      extraction method for blood plasma compatible with standard 96-well robots. In
      only 60 min, 96 samples can be automatically extracted with lipid profiles of
      commonly analyzed lipid classes almost identically and with absolute recoveries
      similar or better to what is obtained using the chloroform-based reference
      method. Lipid recoveries were linear from 10-100 ul plasma for all investigated
      lipids using the developed extraction protocol. The BUME protocol includes an
      initial one-phase extraction of plasma into 300 ul butanol:methanol (BUME)
      mixture (3:1) followed by two-phase extraction into 300 ul heptane:ethyl acetate
      (3:1) using 300 ul 1% acetic acid as buffer. The lipids investigated included the
      most abundant plasma lipid classes (e.g., cholesterol ester, free cholesterol,
      triacylglycerol, phosphatidylcholine, and sphingomyelin) as well as less abundant
      but biologically important lipid classes, including ceramide, diacylglycerol, and
      lyso-phospholipids. This novel method has been successfully implemented in our
      laboratory and is now used daily. We conclude that the fully automated, high
      throughput BUME method can replace chloroform-based methods, saving both human
      and environmental resources.

PMID- 22645249
TI  - Involvement of AMP-activated protein kinase in thrombin-stimulated interleukin 6
      synthesis in osteoblasts.
AB  - We previously demonstrated that thrombin stimulates synthesis of interleukin 6
      (IL6), a potent bone resorptive agent, in part via p44/p42 MAP kinase and p38 MAP
      kinase but not through stress-activated protein kinase/c-Jun N-terminal kinase
      (SAPK/JNK) among the MAP kinase superfamily in osteoblast-like MC3T3-E1 cells. In
      this study, we investigated the involvement of AMP-activated protein kinase
      (AMPK), a regulator of energy metabolism, in thrombin-stimulated IL6 synthesis in
      MC3T3-E1 cells. The phosphorylation of p44/p42 MAP kinase, p38 MAP kinase,
      SAPK/JNK, or AMPK was determined by western blot analysis. The release of IL6 was
      determined by the measurement of IL6 concentration in the conditioned medium
      using an ELISA kit. The expression of IL6 mRNA was determined by RT-PCR. Thrombin
      time dependently induced the phosphorylation of AMPK alpha-subunit (Thr-172).
      Compound C, an inhibitor of AMPK, dose-dependently suppressed the thrombin
      stimulated IL6 release in the range between 0.3 and 10  MUM. Compound C reduced
      thrombin-induced acetyl-CoA carboxylase phosphorylation. The IL6 mRNA expression
      induced by thrombin was markedly reduced by compound C. Downregulation of AMPK by
      siRNA suppressed the thrombin-stimulated IL6 release. The thrombin-induced
      phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was inhibited by
      compound C, which failed to affect SAPK/JNK phosphorylation. These results
      strongly suggest that AMPK regulates thrombin-stimulated IL6 synthesis via
      p44/p42 MAP kinase and p38 MAP kinase in osteoblasts.

PMID- 22645250
TI  - Complementary role of frontoparietal activity and cortical pattern similarity in
      successful episodic memory encoding.
AB  - One central goal in cognitive neuroscience of learning and memory is to
      characterize the neural processes that lead to long-lasting episodic memory. In
      addition to the stronger frontoparietal activity, greater category- or item
      specific cortical representation during encoding, as measured by pattern
      similarity (PS), is also associated with better subsequent episodic memory.
      Nevertheless, it is unknown whether frontoparietal activity and cortical PS
      reflect distinct mechanisms. To address this issue, we reanalyzed previous data
      (Xue G, Dong Q, Chen C, Lu ZL, Mumford JA, Poldrack RA. 2010. Greater neural
      pattern similarity across repetitions is associated with better memory. Science.
      330:97, Experiment 3) using a novel approach based on combined activation-based
      and information-based analyses. The results showed that across items, stronger
      frontoparietal activity was associated with greater PS in distributed brain
      regions, including those where the PS was predictive of better subsequent memory.
      Nevertheless, the item-specific PS was still associated with later episodic
      memory after controlling the effect of frontoparietal activity. Our results
      suggest that one possible mechanism of frontoparietal activity on episodic memory
      encoding is via enhancing PS, resulting in more unique and consistent input to
      the medial temporal lobe. In addition, they suggest that PS might index
      additional processes, such as pattern reinstatement as a result of study-phase
      retrieval, that contribute to episodic memory encoding.

PMID- 22645251
TI  - The role of hippocampal iron concentration and hippocampal volume in age-related
      differences in memory.
AB  - The goal of this study was to examine the relationships between 2 age-sensitive
      indices of brain integrity--volume and iron concentration--and the associated age
      differences in memory performance. In 113 healthy adults (age 19-83 years), we
      measured the volume and estimated iron concentration in the hippocampus (HC),
      caudate nucleus (Cd), and primary visual cortex (VC) in vivo with T2* relaxation
      times, and assessed memory performance with multiple tests. We applied structural
      equation modeling to evaluate the contribution of individual differences in 2
      indices of integrity, volume and T2*, to age-related memory variance. The results
      show that in healthy adults, age differences in memory can be explained in part
      by individual differences in HC volume that in turn are associated with
      differences in HC iron concentration. Lower memory scores were linked to smaller
      HC and higher HC iron concentration. No such associations were noted for Cd and
      VC. We conclude that the association between age-related declines in memory and
      reduced hippocampal volume may reflect the impact of oxidative stress related to
      increase in free iron concentration. Longitudinal follow-up is needed to test
      whether altered iron homeostasis in the HC is an early marker for age-related
      cognitive decline.

PMID- 22645252
TI  - Dopamine-dependent architecture of cortico-subcortical network connectivity.
AB  - Maladaptive dopaminergic mediation of reward processing in humans is thought to
      underlie multiple neuropsychiatric disorders, including addiction, Parkinson's
      disease, and schizophrenia. Mechanisms responsible for the development of such
      disorders may depend on individual differences in neural signaling within large
      scale cortico-subcortical circuitry. Using a combination of functional
      neuroimaging and pharmacological challenges in healthy volunteers, we identified
      opposing dopamine agonistic and antagonistic neuromodulatory effects on
      distributed functional interactions between specific subcortical regions and
      corresponding neocortical "resting-state" networks, known to be involved in
      distinct aspects of cognition and reward processing. We found that, relative to a
      placebo, levodopa and haloperidol challenges, respectively, increased or
      decreased the functional connectivity between (1) the midbrain and a "default
      mode" network, (2) the right caudate and a right-lateralized frontoparietal
      network, and (3) the ventral striatum and a fronto-insular network. Further, we
      found drug-specific associations between brain circuitry reactivity to dopamine
      modulation and individual differences in trait impulsivity, revealing dissociable
      drug-personality interaction effects across distinct dopamine-dependent cortico
      subcortical networks. Our findings identify possible systems underlying
      pathogenesis and treatment efficacy in disorders of dopamine deficiency.

PMID- 22645254
TI  - Impact Commentaries. A modern perspective on the top 100 cited JNNP papers of all
      time: The relevance of the Lewy body to the pathogenesis of idiopathic
      Parkinson's disease: accuracy of clinical diagnosis of idiopathic Parkinson's
      disease.

PMID- 22645253
TI  - Impulsivity and the modular organization of resting-state neural networks.
AB  - Impulsivity is a complex trait associated with a range of maladaptive behaviors,
      including many forms of psychopathology. Previous research has implicated
      multiple neural circuits and neurotransmitter systems in impulsive behavior, but
      the relationship between impulsivity and organization of whole-brain networks has
      not yet been explored. Using graph theory analyses, we characterized the
      relationship between impulsivity and the functional segregation ("modularity") of
      the whole-brain network architecture derived from resting-state functional
      magnetic resonance imaging (fMRI) data. These analyses revealed remarkable
      differences in network organization across the impulsivity spectrum.
      Specifically, in highly impulsive individuals, regulatory structures including
      medial and lateral regions of the prefrontal cortex were isolated from
      subcortical structures associated with appetitive drive, whereas these brain
      areas clustered together within the same module in less impulsive individuals.
      Further exploration of the modular organization of whole-brain networks revealed
      novel shifts in the functional connectivity between visual, sensorimotor,
      cortical, and subcortical structures across the impulsivity spectrum. The current
      findings highlight the utility of graph theory analyses of resting-state fMRI
      data in furthering our understanding of the neurobiological architecture of
      complex behaviors.

PMID- 22645255
TI  - A 'web app' for diagnosing hemianopia.
AB  - BACKGROUND: Hemianopia commonly complicates stroke and, less frequently, head
      injury and brain tumours. Patients' activities of daily living are often affected
      although these can be ameliorated by appropriate behavioural therapy. Identifying
      a field defect is the first step in the rehabilitation process. An online visual
      field test (an 'app') was developed as part of a free to use web based therapy
      site for patients with hemianopic alexia, called Read-Right
      (http://www.readright.ucl.ac.uk). This study is an attempt to validate this test
      by comparing with a clinical 'gold standard'-the Humphrey automated visual field
      analyser. METHODS: 22 patients had their visual fields assessed with both
      techniques on the same day. The criterion validity of the Read-Right was examined
      by comparing it with Humphrey 10-2 and 24-2 perimetry using the following
      measures: (1) sensitivity and specificity; (2) kappa statistics; and (3)
      intraclass correlation. RESULTS: Read-Right demonstrated high sensitivity and
      specificity, particularly for the undamaged field. In the damaged field, kappa
      values were highly significant, especially for points along the horizontal
      meridian. The intraclass correlation score for the damaged field indicated
      excellent correlation between the two tests. Read-Right perimetry performed well
      on all measures. It had a tendency to under call damaged points offset from the
      horizontal meridian, and this and other aspects of the test will be revamped.
      CONCLUSION: Read-Right is not designed to replace standardised visual perimetry;
      it does, however, offer a quick and easy assessment that can be used to screen
      patients. The test is available as part of two free to use web based therapy
      applications.

PMID- 22645256
TI  - Disability in young people and adults after head injury: 12-14 year follow-up of
      a prospective cohort.
AB  - BACKGROUND: There is a need to establish how long term outcome evolves after head
      injury (HI) and factors related to this, to inform opportunities for
      intervention. OBJECTIVE: To determine late outcome in adults 12-14 years after
      hospital admission for HI and to examine relationships between injury, early and
      late factors, and disability. METHODS: A prospective cohort with HI, whose
      outcome was reported previously at 1 and 5-7 years after injury, were followed up
      after 12-14 years. Participants were assessed using structured and validated
      measures of disability (Glasgow Outcome Scale-Extended), psychological well
      being, alcohol use and health status. RESULTS: Of 219 survivors followed-up at 5
      7 years, 34 (15.5%) had died by 12-14 years. Disability remained common in
      survivors at 12-14 years (51%), as found at 1 and 5-7 years (53%). For those
      disabled at 1 year, outcome was poor, with 80% dead or disabled at 12-14 years.
      Older age at injury, a premorbid history of brain illness or physical disability
      and post-injury low self-esteem and stress were associated with disability at 12
      14 years. Disability changed between 5-7 and 12-14 years in 55% of survivors,
      improving in 23%. Late changes in disability between 5-7 and 12-14 years were
      associated with self-perceptions of locus of control as being 'powerful others'
      at 5-7 years. CONCLUSIONS: Disability is common 12-14 years after hospital
      admission with a HI. For some there is a dynamic process of change in disability
      over time that is associated with self-perceptions of control that could be a
      target for intervention based research.

PMID- 22645257
TI  - Visuospatial deficits in posterior cortical atrophy: structural and functional
      correlates.
AB  - OBJECTIVE: To determine the neural substrates of biased spatial orienting in
      posterior cortical atrophy (PCA) by using a combined structural and functional
      neuroimaging approach. BACKGROUND: Patients with spatial neglect typically bisect
      horizontal long lines towards their brain lesions but the precise neural
      substrates of this spatial bias remain controversial and poorly explored in
      neurodegenerative disorders such as PCA. METHODS: 15 patients with PCA underwent
      brain MRI and single photon emission computed tomography (SPECT) and were
      required to bisect five 20 cm long lines, each centred on an A4 horizontal sheet.
      Direct correlations between average deviations on the bisection task and both (1)
      the degree of grey matter density, as estimated by voxel based morphometry and
      (2) regional cerebral blood flow, as assessed by SPECT, were performed. RESULTS:
      Seven patients (47%) had pathological bias on the bisection task, deviating
      consistently towards the non-neglected side for each of the five lines. Rightward
      bias (sign of left-sided neglect) was more frequent and severe than leftward bias
      (sign of right-sided neglect). Correlation analyses showed that rightward
      deviations correlated with atrophy and hypoperfusion exclusively in the right
      hemisphere, involving a large scale fronto-parietal network; cortical atrophy was
      prominent in the parieto-temporal cortex but extended to the frontal region;
      hypoperfusion was substantial both in the middle frontal gyrus and in the
      postcentral region. No correlations emerged from leftward deviations. CONCLUSION:
      The results indicate that rightward bias (sign of left-sided neglect) in PCA
      depends on dysfunction of a large fronto-parietal network in the right
      hemisphere, related to both cortical atrophy and decreased cerebral perfusion.

PMID- 22645258
TI  - Random X inactivation in the mule and horse placenta.
AB  - In eutherian mammals, dosage compensation of X-linked genes is achieved by X
      chromosome inactivation. X inactivation is random in embryonic and adult tissues,
      but imprinted X inactivation (paternal X silencing) has been identified in the
      extra-embryonic membranes of the mouse, rat, and cow. Few other species have been
      studied for this trait, and the data from studies of the human placenta have been
      discordant or inconclusive. Here, we quantify X inactivation using RNA sequencing
      of placental tissue from reciprocal hybrids of horse and donkey (mule and hinny).
      In placental tissue from the equid hybrids and the horse parent, the allelic
      expression pattern was consistent with random X inactivation, and imprinted X
      inactivation can clearly be excluded. We characterized horse and donkey XIST gene
      and demonstrated that XIST allelic expression in female hybrid placental and
      fetal tissues is negatively correlated with the other X-linked genes chromosome
      wide, which is consistent with the XIST-mediated mechanism of X inactivation
      discovered previously in mice. As the most structurally and morphologically
      diverse organ in mammals, the placenta also appears to show diverse mechanisms
      for dosage compensation that may result in differences in conceptus development
      across species.

PMID- 22645259
TI  - Genomic characterization of the Bacillus cereus sensu lato species: backdrop to
      the evolution of Bacillus anthracis.
AB  - The key genes required for Bacillus anthracis to cause anthrax have been acquired
      recently by horizontal gene transfer. To understand the genetic background for
      the evolution of B. anthracis virulence, we obtained high-redundancy genome
      sequences of 45 strains of the Bacillus cereus sensu lato (s.l.) species that
      were chosen for their genetic diversity within the species based on the existing
      multilocus sequence typing scheme. From the resulting data, we called more than
      324,000 new genes representing more than 12,333 new gene families for this group.
      The core genome size for the B. cereus s.l. group was ~1750 genes, with another
      2150 genes found in almost every genome constituting the extended core. There was
      a paucity of genes specific and conserved in any clade. We found no evidence of
      recent large-scale gene loss in B. anthracis or for unusual accumulation of
      nonsynonymous DNA substitutions in the chromosome; however, several B. cereus
      genomes isolated from soil and not previously associated with human disease were
      degraded to various degrees. Although B. anthracis has undergone an ecological
      shift within the species, its chromosome does not appear to be exceptional on a
      macroscopic scale compared with close relatives.

PMID- 22645260
TI  - Polygenic cis-regulatory adaptation in the evolution of yeast pathogenicity.
AB  - The acquisition of new genes, via horizontal transfer or gene
      duplication/diversification, has been the dominant mechanism thus far implicated
      in the evolution of microbial pathogenicity. In contrast, the role of many other
      modes of evolution--such as changes in gene expression regulation-remains
      unknown. A transition to a pathogenic lifestyle has recently taken place in some
      lineages of the budding yeast Saccharomyces cerevisiae. Here we identify a module
      of physically interacting proteins involved in endocytosis that has experienced
      selective sweeps for multiple cis-regulatory mutations that down-regulate gene
      expression levels in a pathogenic yeast. To test if these adaptations affect
      virulence, we created a panel of single-allele knockout strains whose hemizygous
      state mimics the genes' adaptive down-regulations, and measured their virulence
      in a mammalian host. Despite having no growth advantage in standard laboratory
      conditions, nearly all of the strains were more virulent than their wild-type
      progenitor, suggesting that these adaptations likely played a role in the
      evolution of pathogenicity. Furthermore, genetic variants at these loci were
      associated with clinical origin across 88 diverse yeast strains, suggesting the
      adaptations may have contributed to the virulence of a wide range of clinical
      isolates. We also detected pleiotropic effects of these adaptations on a wide
      range of morphological traits, which appear to have been mitigated by
      compensatory mutations at other loci. These results suggest that cis-regulatory
      adaptation can occur at the level of physically interacting modules and that one
      such polygenic adaptation led to increased virulence during the evolution of a
      pathogenic yeast.

PMID- 22645261
TI  - A-to-I editing of microRNAs in the mammalian brain increases during development.
AB  - Adenosine-to-inosine (A-to-I) RNA editing targets double-stranded RNA stem-loop
      structures in the mammalian brain. It has previously been shown that miRNAs are
      substrates for A-to-I editing. For the first time, we show that for several
      definitions of edited miRNA, the level of editing increases with development,
      thereby indicating a regulatory role for editing during brain maturation. We use
      high-throughput RNA sequencing to determine editing levels in mature miRNA, from
      the mouse transcriptome, and compare these with the levels of editing in pri
      miRNA. We show that increased editing during development gradually changes the
      proportions of the two miR-376a isoforms, which previously have been shown to
      have different targets. Several other miRNAs that also are edited in the seed
      sequence show an increased level of editing through development. By comparing
      editing of pri-miRNA with editing and expression of the corresponding mature
      miRNA, we also show an editing-induced developmental regulation of miRNA
      expression. Taken together, our results imply that RNA editing influences the
      miRNA repertoire during brain maturation.

PMID- 22645262
TI  - Vibro- and electrotactile user feedback on hand opening for myoelectric forearm
      prostheses.
AB  - Many of the currently available myoelectric forearm prostheses stay unused
      because of the lack of sensory feedback. Vibrotactile and electrotactile
      stimulation have high potential to provide this feedback. In this study,
      performance of a grasping task is investigated for different hand opening
      feedback conditions on 15 healthy subjects and validated on three patients. The
      opening of a virtual hand was controlled by a scroll wheel. Feedback about hand
      opening was given via an array of eight vibrotactile or electrotactile
      stimulators placed on the forearm, relating to eight hand opening positions. A
      longitudinal and transversal orientation of the array and four feedback
      conditions were investigated: no feedback, visual feedback, feedback through
      vibrotactile or electrotactile stimulation, and addition of an extra stimulator
      for touch feedback. No influence of array orientation was shown for all outcome
      parameters (duration of the task, the percentage of correct hand openings, the
      mean position error, and the percentage deviations up to one position).
      Vibrotactile stimulation enhances the performance compared to the nonfeedback
      conditions. The addition of touch feedback further increases the performance, but
      at the cost of an increased duration. The same effects were found for the patient
      group, but the task duration was around 25% larger.

PMID- 22645263
TI  - Impact of model shape mismatch on reconstruction quality in electrical impedance
      tomography.
AB  - Electrical impedance tomography (EIT) is a low-cost, noninvasive and radiation
      free medical imaging modality for monitoring ventilation distribution in the
      lung. Although such information could be invaluable in preventing ventilator
      induced lung injury in mechanically ventilated patients, clinical application of
      EIT is hindered by difficulties in interpreting the resulting images. One source
      of this difficulty is the frequent use of simple shapes which do not correspond
      to the anatomy to reconstruct EIT images. The mismatch between the true body
      shape and the one used for reconstruction is known to introduce errors, which to
      date have not been properly characterized. In the present study we, therefore,
      seek to 1) characterize and quantify the errors resulting from a reconstruction
      shape mismatch for a number of popular EIT reconstruction algorithms and 2)
      develop recommendations on the tolerated amount of mismatch for each algorithm.
      Using real and simulated data, we analyze the performance of four EIT
      reconstruction algorithms under different degrees of shape mismatch. Results
      suggest that while slight shape mismatch is well tolerated by all algorithms,
      using a circular shape severely degrades their performance.

PMID- 22645264
TI  - MIQM: a multicamera image quality measure.
AB  - Although several subjective and objective quality assessment methods have been
      proposed in the literature for images and videos from single cameras, no
      comparable effort has been devoted to the quality assessment of multicamera
      images. With the increasing popularity of multiview applications, quality
      assessment of multicamera images and videos is becoming fundamental to the
      development of these applications. Image quality is affected by several factors,
      such as camera configuration, number of cameras, and the calibration process. In
      order to develop an objective metric specifically designed for multicamera
      systems, we identified and quantified two types of visual distortions in
      multicamera images: photometric distortions and geometric distortions. The
      relative distortion between individual camera scenes is a major factor in
      determining the overall perceived quality. In this paper, we show that such
      distortions can be translated into luminance, contrast, spatial motion, and edge
      based structure components. We propose three different indices that can quantify
      these components. We provide examples to demonstrate the correlation among these
      components and the corresponding indices. Then, we combine these indices into one
      multicamera image quality measure (MIQM). Results and comparisons with other
      measures, such as peak signal-to noise ratio, mean structural similarity, and
      visual information fidelity show that MIQM outperforms other measures in
      capturing the perceptual fidelity of multicamera images. Finally, we verify the
      results against subjective evaluation.

PMID- 22645265
TI  - Efficient image denoising method based on a new adaptive wavelet packet
      thresholding function.
AB  - This paper proposes a statistically optimum adaptive wavelet packet (WP)
      thresholding function for image denoising based on the generalized Gaussian
      distribution. It applies computationally efficient multilevel WP decomposition to
      noisy images to obtain the best tree or optimal wavelet basis, utilizing Shannon
      entropy. It selects an adaptive threshold value which is level and subband
      dependent based on analyzing the statistical parameters of subband coefficients.
      In the utilized thresholding function, which is based on a maximum a posteriori
      estimate, the modified version of dominant coefficients was estimated by optimal
      linear interpolation between each coefficient and the mean value of the
      corresponding subband. Experimental results, on several test images under
      different noise intensity conditions, show that the proposed algorithm, called
      OLI-Shrink, yields better peak signal noise ratio and superior visual image
      quality-measured by universal image quality index-compared to standard denoising
      methods, especially in the presence of high noise intensity. It also outperforms
      some of the best state-of-the-art wavelet-based denoising techniques.

PMID- 22645266
TI  - Foreground object detection using top-down information based on EM framework.
AB  - In this paper, we present a novel foreground object detection scheme that
      integrates the top-down information based on the expectation maximization (EM)
      framework. In this generalized EM framework, the top-down information is
      incorporated in an object model. Based on the object model and the state of each
      target, a foreground model is constructed. This foreground model can augment the
      foreground detection for the camouflage problem. Thus, an object's state-specific
      Markov random field (MRF) model is constructed for detection based on the
      foreground model and the background model. This MRF model depends on the latent
      variables that describe each object's state. The maximization of the MRF model is
      the M-step in the EM framework. Besides fusing spatial information, this MRF
      model can also adjust the contribution of the top-down information for detection.
      To obtain detection result using this MRF model, sampling importance resampling
      is used to sample the latent variable and the EM framework refines the detection
      iteratively. Besides the proposed generalized EM framework, our method does not
      need any prior information of the moving object, because we use the detection
      result of moving object to incorporate the domain knowledge of the object shapes
      into the construction of top-down information. Moreover, in our method, a kernel
      density estimation (KDE)-Gaussian mixture model (GMM) hybrid model is proposed to
      construct the probability density function of background and moving object model.
      For the background model, it has some advantages over GMM- and KDE-based methods.
      Experimental results demonstrate the capability of our method, particularly in
      handling the camouflage problem.

PMID- 22645267
TI  - Performance comparisons of contour-based corner detectors.
AB  - Corner detectors have many applications in computer vision and image
      identification and retrieval. Contour-based corner detectors directly or
      indirectly estimate a significance measure (e.g., curvature) on the points of a
      planar curve, and select the curvature extrema points as corners. While an
      extensive number of contour-based corner detectors have been proposed over the
      last four decades, there is no comparative study of recently proposed detectors.
      This paper is an attempt to fill this gap. The general framework of contour-based
      corner detection is presented, and two major issues-curve smoothing and curvature
      estimation, which have major impacts on the corner detection performance, are
      discussed. A number of promising detectors are compared using both automatic and
      manual evaluation systems on two large datasets. It is observed that while the
      detectors using indirect curvature estimation techniques are more robust, the
      detectors using direct curvature estimation techniques are faster.

PMID- 22645268
TI  - 3-D modeling from a single view of a symmetric object.
AB  - 3-D technologies are considered as the next generation of multimedia
      applications. Currently, one of the challenges faced by 3-D applications is the
      shortage of 3-D resources. To solve this problem, many 3-D modeling methods are
      proposed to directly recover 3-D geometry from 2-D images. However, these methods
      on single view modeling either require intensive user interaction, or are
      restricted to a specific kind of object. In this paper, we propose a novel 3-D
      modeling approach to recover 3-D geometry from a single image of a symmetric
      object with minimal user interaction. Symmetry is one of the most common
      properties of natural or manmade objects. Given a single view of a symmetric
      object, the user marks some symmetric lines and depth discontinuity regions on
      the image. Our algorithm first finds a set of planes to approximately fit to the
      object, and then a rough 3-D point cloud is generated by an optimization
      procedure. The occluded part of the object is further recovered using symmetry
      information. Experimental results on various indoor and outdoor objects show that
      the proposed system can obtain 3-D models from single images with only a little
      user interaction.

PMID- 22645269
TI  - Bayesian technique for image classifying registration.
AB  - In this paper, we address a complex image registration issue arising while the
      dependencies between intensities of images to be registered are not spatially
      homogeneous. Such a situation is frequently encountered in medical imaging when a
      pathology present in one of the images modifies locally intensity dependencies
      observed on normal tissues. Usual image registration models, which are based on a
      single global intensity similarity criterion, fail to register such images, as
      they are blind to local deviations of intensity dependencies. Such a limitation
      is also encountered in contrast-enhanced images where there exist multiple pixel
      classes having different properties of contrast agent absorption. In this paper,
      we propose a new model in which the similarity criterion is adapted locally to
      images by classification of image intensity dependencies. Defined in a Bayesian
      framework, the similarity criterion is a mixture of probability distributions
      describing dependencies on two classes. The model also includes a class map which
      locates pixels of the two classes and weighs the two mixture components. The
      registration problem is formulated both as an energy minimization problem and as
      a maximum a posteriori estimation problem. It is solved using a gradient descent
      algorithm. In the problem formulation and resolution, the image deformation and
      the class map are estimated simultaneously, leading to an original combination of
      registration and classification that we call image classifying registration.
      Whenever sufficient information about class location is available in
      applications, the registration can also be performed on its own by fixing a given
      class map. Finally, we illustrate the interest of our model on two real
      applications from medical imaging: template-based segmentation of contrast
      enhanced images and lesion detection in mammograms. We also conduct an evaluation
      of our model on simulated medical data and show its ability to take into account
      spatial variations of intensity dependencies while keeping a good registration
      accuracy.

PMID- 22645270
TI  - Optimized regression for efficient function evaluation.
AB  - In many applications of regression, one is concerned with the efficiency of the
      estimated function in addition to the accuracy of the regression. For efficiency,
      it is common to represent the estimated function as a rectangular lattice of
      values-a lookup table (LUT)-that can be linearly interpolated for any needed
      value. Typically, a LUT is constructed from data with a two-step process that
      first fits a function to the data, then evaluates that fitted function at the
      nodes of the lattice. We present an approach, termed lattice regression, that
      directly optimizes the values of the lattice nodes to minimize the post
      interpolation training error. Additionally, we propose a second-order difference
      regularizer to promote smoothness. We demonstrate the effectiveness of this
      approach on two image processing tasks that require both accurate regression and
      efficient function evaluations: inverse device characterization for color
      management and omnidirectional super-resolution for visual homing.

PMID- 22645271
TI  - Bi-exponential edge-preserving smoother.
AB  - Edge-preserving smoothers need not be taxed by a severe computational cost. We
      present, in this paper, a lean algorithm that is inspired by the bi-exponential
      filter and preserves its structure-a pair of one-tap recursions. By a careful but
      simple local adaptation of the filter weights to the data, we are able to design
      an edge-preserving smoother that has a very low memory and computational
      footprint while requiring a trivial coding effort. We demonstrate that our filter
      (a bi-exponential edge-preserving smoother, or BEEPS) has formal links with the
      traditional bilateral filter. On a practical side, we observe that the BEEPS also
      produces images that are similar to those that would result from the bilateral
      filter, but at a much-reduced computational cost. The cost per pixel is constant
      and depends neither on the data nor on the filter parameters, not even on the
      degree of smoothing.

PMID- 22645272
TI  - Feature selection with harmony search.
AB  - Many search strategies have been exploited for the task of feature selection
      (FS), in an effort to identify more compact and better quality subsets. Such work
      typically involves the use of greedy hill climbing (HC), or nature-inspired
      heuristics, in order to discover the optimal solution without going through
      exhaustive search. In this paper, a novel FS approach based on harmony search
      (HS) is presented. It is a general approach that can be used in conjunction with
      many subset evaluation techniques. The simplicity of HS is exploited to reduce
      the overall complexity of the search process. The proposed approach is able to
      escape from local solutions and identify multiple solutions owing to the
      stochastic nature of HS. Additional parameter control schemes are introduced to
      reduce the effort and impact of parameter configuration. These can be further
      combined with the iterative refinement strategy, tailored to enforce the
      discovery of quality subsets. The resulting approach is compared with those that
      rely on HC, genetic algorithms, and particle swarm optimization, accompanied by
      in-depth studies of the suggested improvements.

PMID- 22645273
TI  - Linearithmic time sparse and convex maximum margin clustering.
AB  - Recently, a new clustering method called maximum margin clustering (MMC) was
      proposed and has shown promising performances. It was originally formulated as a
      difficult nonconvex integer problem. To make the MMC problem practical, the
      researchers either relaxed the original MMC problem to inefficient convex
      optimization problems or reformulated it to nonconvex optimization problems,
      which sacrifice the convexity for efficiency. However, no approaches can both
      hold the convexity and be efficient. In this paper, a new linearithmic time
      sparse and convex MMC algorithm, called support-vector-regression-based MMC (SVR
      MMC), is proposed. Generally, it first uses the SVR as the core of the MMC. Then,
      it is relaxed as a convex optimization problem, which is iteratively solved by
      the cutting-plane algorithm. Each cutting-plane subproblem is further decomposed
      to a serial supervised SVR problem by a new global extended-level method (GELM).
      Finally, each supervised SVR problem is solved in a linear time complexity by a
      new sparse-kernel SVR (SKSVR) algorithm. We further extend the SVR-MMC algorithm
      to the multiple-kernel clustering (MKC) problem and the multiclass MMC (M3C)
      problem, which are denoted as SVR-MKC and SVR-M3C, respectively. One key point of
      the algorithms is the utilization of the SVR. It can prevent the MMC and its
      extensions meeting an integer matrix programming problem. Another key point is
      the new SKSVR. It provides a linear time interface to the nonlinear kernel
      scenarios, so that the SVR-MMC and its extensions can keep a linearthmic time
      complexity in nonlinear kernel scenarios. Our experimental results on various
      real-world data sets demonstrate the effectiveness and the efficiency of the SVR
      MMC and its two extensions. Moreover, the unsupervised application of the SVR-MKC
      to the voice activity detection (VAD) shows that the SVR-MKC can achieve good
      performances that are close to its supervised counterpart, meet the real-time
      demand of the VAD, and need no labeling for model training.

PMID- 22645274
TI  - An adaptive window-setting scheme for segmentation of bladder tumor surface via
      MR cystography.
AB  - This paper proposes an adaptive window-setting scheme for noninvasive detection
      and segmentation of bladder tumor surface in T(1)-weighted magnetic resonance
      (MR) images. The inner border of the bladder wall is first covered by a group of
      ball-shaped detecting windows with different radii. By extracting the candidate
      tumor windows and excluding the false positive (FP) candidates, the entire
      bladder tumor surface is detected and segmented by the remaining windows.
      Different from previous bladder tumor detection methods that are mostly focusing
      on the existence of a tumor, this paper emphasizes segmenting the entire tumor
      surface in addition to detecting the presence of the tumor. The presented scheme
      was validated by ten clinical T(1)-weighted MR image datasets (five volunteers
      and five patients). The bladder tumor surfaces and the normal bladder wall inner
      borders in the ten datasets were covered by 223 and 10,491 windows, respectively.
      Such a large number of the detecting windows makes the validation statistically
      meaningful. In the FP reduction step, the best feature combination was obtained
      by using receiver operating characteristics or ROC analysis. The validation
      results demonstrated the potential of this presented scheme in segmenting the
      entire tumor surface with high sensitivity and low FP rate. This study inherits
      our previous results of automatic segmentation of the bladder wall and will be an
      important element in our MR-based virtual cystoscopy or MR cystography system.

PMID- 22645275
TI  - Identification of novel ATP13A2 interactors and their role in alpha-synuclein
      misfolding and toxicity.
AB  - Lysosomes are responsible for degradation and recycling of bulky cell material,
      including accumulated misfolded proteins and dysfunctional organelles. Increasing
      evidence implicates lysosomal dysfunction in several neurodegenerative disorders,
      including Parkinson's disease and related synucleinopathies, which are
      characterized by the accumulation of alpha-synuclein (alpha-syn) in Lewy bodies.
      Studies of lysosomal proteins linked to neurodegenerative disorders present an
      opportunity to uncover specific molecular mechanisms and pathways that contribute
      to neurodegeneration. Loss-of-function mutations in a lysosomal protein, ATP13A2
      (PARK9), cause Kufor-Rakeb syndrome that is characterized by early-onset
      parkinsonism, pyramidal degeneration and dementia. While loss of ATP13A2 function
      plays a role in alpha-syn misfolding and toxicity, the normal function of ATP13A2
      in the brain remains largely unknown. Here, we performed a screen to identify
      ATP13A2 interacting partners, as a first step toward elucidating its function.
      Utilizing a split-ubiquitin membrane yeast two-hybrid system that was developed
      to identify interacting partners of full-length integral membrane proteins, we
      identified 43 novel interactors that primarily implicate ATP13A2 in cellular
      processes such as endoplasmic reticulum (ER) translocation, ER-to-Golgi
      trafficking and vesicular transport and fusion. We showed that a subset of these
      interactors modified alpha-syn aggregation and alpha-syn-mediated degeneration of
      dopaminergic neurons in Caenorhabditis elegans, further suggesting that ATP13A2
      and alpha-syn are functionally linked in neurodegeneration. These results
      implicate ATP13A2 in vesicular trafficking and provide a platform for further
      studies of ATP13A2 in neurodegeneration.

PMID- 22645277
TI  - Evidence for an oligogenic basis of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a
      substantial heritable component. In pedigrees affected by its familial form,
      incomplete penetrance is often observed. We hypothesized that this could be
      caused by a complex inheritance of risk variants in multiple genes. Therefore, we
      screened 111 familial ALS (FALS) patients from 97 families, and large cohorts of
      sporadic ALS (SALS) patients and control subjects for mutations in TAR DNA
      binding protein (TARDBP), fused in sarcoma/translated in liposarcoma (FUS/TLS),
      superoxide dismutase-1 (SOD1), angiogenin (ANG) and chromosome 9 open reading
      frame 72 (C9orf72). Mutations were identified in 48% of FALS families, 8% of SALS
      patients and 0.5% of control subjects. In five of the FALS families, we
      identified multiple mutations in ALS-associated genes. We detected FUS/TLS and
      TARDBP mutations in combination with ANG mutations, and C9orf72 repeat expansions
      with TARDBP, SOD1 and FUS/TLS mutations. Statistical analysis demonstrated that
      the presence of multiple mutations in FALS is in excess of what is to be expected
      by chance (P = 1.57 * 10(-7)). The most compelling evidence for an oligogenic
      basis was found in individuals with a p.N352S mutation in TARDBP, detected in
      five FALS families and three apparently SALS patients. Genealogical and haplotype
      analyses revealed that these individuals shared a common ancestor. We obtained
      DNA of 14 patients with this TARDBP mutation, 50% of whom had an additional
      mutation (ANG, C9orf72 or homozygous TARDBP). Hereby, we provide evidence for an
      oligogenic aetiology of ALS. This may have important implications for the
      interpretation of whole exome/genome experiments designed to identify new ALS
      associated genes and for genetic counselling, especially of unaffected family
      members.

PMID- 22645278
TI  - Bisphenol A and peripheral arterial disease: results from the NHANES.
AB  - BACKGROUND: Bisphenol A (BPA) is a common chemical used in the manufacture of
      polycarbonate plastics and epoxy resins, and > 93% of U.S. adults have detectable
      levels of urinary BPA. Recent animal studies have suggested that BPA exposure may
      have a role in several mechanisms involved in the development of cardiovascular
      disease (CVD), including weight gain, insulin resistance, thyroid dysfunction,
      endothelial dysfunction, and oxidative stress. However, few human studies have
      examined the association between markers of BPA exposure and CVD. Peripheral
      arterial disease (PAD) is a subclinical measure of atherosclerotic vascular
      disease and a strong independent risk factor for CVD and mortality. OBJECTIVE: We
      examined the association between urinary BPA levels and PAD in a nationally
      representative sample of U.S. adults. METHODS: We analyzed data from 745
      participants in the National Health and Nutritional Examination Survey 2003-2004.
      We estimated associations between urinary BPA levels (in tertiles) and PAD (ankle
      brachial index < 0.9, n = 63) using logistic regression models adjusted for
      potential confounders (age, sex, race/ethnicity, education, smoking, body mass
      index, diabetes mellitus, hypertension, urinary creatinine, estimated glomerular
      filtration rate, and serum cholesterol levels). RESULTS: We observed a
      significant, positive association between increasing levels of urinary BPA and
      PAD before and after adjusting for confounders. The multivariable-adjusted odds
      ratio for PAD associated with the highest versus lowest tertile of urinary BPA
      was 2.69 (95% confidence interval: 1.02, 7.09; p-trend = 0.01). CONCLUSIONS:
      Urinary BPA levels were significantly associated with PAD, independent of
      traditional CVD risk factors.

PMID- 22645276
TI  - ATOH7 mutations cause autosomal recessive persistent hyperplasia of the primary
      vitreous.
AB  - The vertebrate basic helix-loop-helix (bHLH) transcription factor ATOH7 (Math5)
      is specifically expressed in the embryonic neural retina and is required for the
      genesis of retinal ganglion cells (RGCs) and optic nerves. In Atoh7 mutant mice,
      the absence of trophic factors secreted by RGCs prevents the development of the
      intrinsic retinal vasculature and the regression of fetal blood vessels, causing
      persistent hyperplasia of the primary vitreous (PHPV). We therefore screened
      patients with hereditary PHPV, as well as bilateral optic nerve aplasia (ONA) or
      hypoplasia (ONH), for mutations in ATOH7. We identified a homozygous ATOH7
      mutation (N46H) in a large family with an autosomal recessive PHPV disease trait
      linked to 10q21, and a heterozygous variant (R65G, p.Arg65Gly) in one of five
      sporadic ONA patients. High-density single-nucleotide polymorphism analysis also
      revealed a CNTN4 duplication and an OTX2 deletion in the ONA cohort. Functional
      analysis of ATOH7 bHLH domain substitutions, by electrophoretic mobility shift
      and luciferase cotransfection assays, revealed that the N46H variant cannot bind
      DNA or activate transcription, consistent with structural modeling. The N46H
      variant also failed to rescue RGC development in mouse Atoh7-/- retinal explants.
      The R65G variant retains all of these activities, similar to wild-type human
      ATOH7. Our results strongly suggest that autosomal recessive persistent
      hyperplastic primary vitreous is caused by N46H and is etiologically related to
      nonsyndromic congenital retinal nonattachment. The R65G allele, however, cannot
      explain the ONA phenotype. Our study firmly establishes ATOH7 as a retinal
      disease gene and provides a functional basis to analyze new coding variants.

PMID- 22645279
TI  - Birth weight following pregnancy during the 2003 Southern California wildfires.
AB  - BACKGROUND: In late October 2003, a series of wildfires exposed urban populations
      in Southern California to elevated levels of air pollution over several weeks.
      Previous research suggests that short-term hospital admissions for respiratory
      outcomes increased specifically as a result of these fires. OBJECTIVE: We
      assessed the impact of a wildfire event during pregnancy on birth weight among
      term infants. METHODS: Using records for singleton term births delivered to
      mothers residing in California's South Coast Air Basin (SoCAB) during 2001-2005
      (n = 886,034), we compared birth weights from pregnancies that took place
      entirely before or after the wildfire event (n = 747,590) with those where
      wildfires occurred during the first (n = 60,270), second (n = 39,435), or third
      (n = 38,739) trimester. The trimester-specific effects of wildfire exposure were
      estimated using a fixed-effects regression model with several maternal
      characteristics included as covariates. RESULTS: Compared with pregnancies before
      and after the wildfires, mean birth weight was estimated to be 7.0 g lower [95%
      confidence interval (CI): -11.8, -2.2] when the wildfire occurred during the
      third trimester, 9.7 g lower when it occurred during the second trimester (95%
      CI: -14.5, -4.8), and 3.3 g lower when it occurred during the first trimester
      (95% CI: -7.2, 0.6). CONCLUSIONS: Pregnancy during the 2003 Southern California
      wildfires was associated with slightly reduced average birth weight among infants
      exposed in utero. The extent and increasing frequency of wildfire events may have
      implications for infant health and development.

PMID- 22645280
TI  - Practical advancement of multipollutant scientific and risk assessment approaches
      for ambient air pollution.
AB  - OBJECTIVES: The U.S. Environmental Protection Agency is working toward gaining a
      better understanding of the human health impacts of exposure to complex air
      pollutant mixtures and the key features that drive the toxicity of these
      mixtures, which can then be used for future scientific and risk assessments. DATA
      SOURCES: A public workshop was held in Chapel Hill, North Carolina, 22-24
      February 2011, to discuss scientific issues and data gaps related to adopting
      multipollutant science and risk assessment approaches, with a particular focus on
      the criteria air pollutants. Expert panelists in the fields of epidemiology,
      toxicology, and atmospheric and exposure sciences led open discussions to
      encourage workshop participants to think broadly about available and emerging
      scientific evidence related to multipollutant approaches to evaluating the health
      effects of air pollution. SYNTHESIS: Although there is clearly a need for novel
      research and analytical approaches to better characterize the health effects of
      multipollutant exposures, much progress can be made by using existing scientific
      information and statistical methods to evaluate the effects of single pollutants
      in a multipollutant context. This work will have a direct impact on the
      development of a multipollutant science assessment and a conceptual framework for
      conducting multipollutant risk assessments. CONCLUSIONS: Transitioning to a
      multipollutant paradigm can be aided through the adoption of a framework for
      multipollutant science and risk assessment that encompasses well-studied and
      ubiquitous air pollutants. Successfully advancing methods for conducting these
      assessments will require collaborative and parallel efforts between the
      scientific and environmental regulatory and policy communities.

PMID- 22645281
TI  - [A medical-pharmaceutical partnership model as a contributor to the success in
      conditioning regimen for allogenic hematopoietic stem cell transplantation in
      adults: a cross-reflection on our organizations].
AB  - Allogeneic hematopoietic stem-cell transplant (allo-SCT) remains the only cure
      for many hematological malignancies and some benign and congenital diseases.
      Busulfan, proposed in its injectable form, has quickly become a mainstay of
      pharmacological and myeloablative (or non-myeloablative) conditioning. This is
      following the outbreak in 2010 of a multicenter international clinical phase II
      trial, we tested the robustness and reliability of our organization in a complex
      model of organization and multifactorial partnership. In this type "BuCy2"
      protocol based on a classical treatment duration of 4 consecutive days, the
      administration of IV busulfan is given in one single daily infusion instead of
      the conventional 16 infusions, while keeping the same total dose. Under these
      conditions, the treatment is totally secured using a therapeutic drug monitoring
      of busulfan, applied in real-time. The process is technically complex and
      requires the very close cooperation of the teams involved. A strength, weakness,
      opportunity and threat (SWOT) analysis has been constructed; it fully supports
      continuous quality improvement to the triple benefit of the nursing chain, the
      patients and their environment. Several critical points were identified and
      corrected. The experiment strongly contributes to the safety and security of the
      medication circuit at the hospital and, improves the performance of allo-SCT. It
      also contributes to the protection of all actors in the health field and their
      working environment via a well-functioning quality management system.

PMID- 22645282
TI  - [Renal carcinoma: point on treatment of brain metastasis].
AB  - Prognosis of patients with renal carcinoma has improved since the advent of
      targeted therapies. These last years, due to the improvement of patients overall
      survival, the incidence of brain metastasis among renal carcinoma patients has
      increased. This worsens the prognosis of patients. The present revue aims to do a
      point on treatment of brain metastasis from renal carcinoma. It will address both
      locoregional (surgery, radiotherapy and stereotactic radiosurgery) and systemic
      (targeted therapies) treatments.

PMID- 22645284
TI  - Localization of Aggregatibacter actinomycetemcomitans cytolethal distending toxin
      subunits during intoxication of live cells.
AB  - The cytolethal distending toxin (Cdt), produced by some clinically important Gram
      negative bacterial species, is related to the family of AB-type toxins. Three
      heterologous proteins (CdtA, CdtB, and CdtC) and a genotoxin mode of action
      distinguish the Cdt from others in this toxin class. Crystal structures of
      several species-specific Cdts have provided a basis for predicting subunit
      interactions and functions. In addition, empirical studies have yielded
      significant insights into the in vivo interactions of the Cdt subunits. However,
      there are still critical gaps in information about the intoxication process. In
      this study, a novel protein tagging technology was used to localize the subunits
      in Chinese hamster ovary cells (CHO-K1). A tetracysteine motif was engineered in
      each subunit, and in subunits with mutations in predicted functional domains, to
      permit detection with the fluorescein arsenical hairpin binding (FlAsH) dye Lumio
      green. Live-cell imaging, in conjunction with confocal microscopy, was used to
      capture the locations of the individual subunits in cells intoxicated, under
      various conditions, with hybrid heterotrimers. Using this approach, we observed
      the following. (i) The CdtA subunit remains on the cell surface of CHO cells in
      association with cholesterol-containing and cholesterol-depleted membrane. (ii)
      The CdtB subunit is exclusively in the cytosol and, after longer exposure times,
      localizes to the nucleus. (iii) The CdtC subunit is present on the cell surface
      and, to a greater extent, in the cytosol. These observations suggest that CdtC,
      but not CdtA, functions as a chaperone for CdtB entry into cells.

PMID- 22645283
TI  - Pneumococcal interactions with epithelial cells are crucial for optimal biofilm
      formation and colonization in vitro and in vivo.
AB  - The human nasopharynx is the main reservoir for Streptococcus pneumoniae (the
      pneumococcus) and the source for both horizontal spread and transition to
      infection. Some clinical evidence indicates that nasopharyngeal carriage is
      harder to eradicate with antibiotics than is pneumococcal invasive disease, which
      may suggest that colonizing pneumococci exist in biofilm communities that are
      more resistant to antibiotics. While pneumococcal biofilms have been observed
      during symptomatic infection, their role in colonization and the role of host
      factors in this process have been less studied. Here, we show for the first time
      that pneumococci form highly structured biofilm communities during colonization
      of the murine nasopharynx that display increased antibiotic resistance.
      Furthermore, pneumococcal biofilms grown on respiratory epithelial cells
      exhibited phenotypes similar to those observed during colonization in vivo,
      whereas abiotic surfaces produced less ordered and more antibiotic-sensitive
      biofilms. The importance of bacterial-epithelial cell interactions during biofilm
      formation was shown using both clinical strains with variable colonization
      efficacies and pneumococcal mutants with impaired colonization characteristics in
      vivo. In both cases, the ability of strains to form biofilms on epithelial cells
      directly correlated with their ability to colonize the nasopharynx in vivo, with
      colonization-deficient strains forming less structured and more antibiotic
      sensitive biofilms on epithelial cells, an association that was lost when grown
      on abiotic surfaces. Thus, these studies emphasize the importance of host
      bacterial interactions in pneumococcal biofilm formation and provide the first
      experimental data to explain the high resistance of pneumococcal colonization to
      eradication by antibiotics.

PMID- 22645285
TI  - Urease activity represents an alternative pathway for Mycobacterium tuberculosis
      nitrogen metabolism.
AB  - Urease represents a critical virulence factor for some bacterial species through
      its alkalizing effect, which helps neutralize the acidic microenvironment of the
      pathogen. In addition, urease serves as a nitrogen source provider for bacterial
      growth. Pathogenic mycobacteria express a functional urease, but its role during
      infection has yet to be characterized. In this study, we constructed a urease
      deficient Mycobacterium tuberculosis strain and confirmed the alkalizing effect
      of the urease activity within the mycobacterium-containing vacuole in resting
      macrophages but not in the more acidic phagolysosomal compartment of activated
      macrophages. However, the urease-mediated alkalizing effect did not confer any
      growth advantage on M. tuberculosis in macrophages, as evidenced by comparable
      growth profiles for the mutant, wild-type (WT), and complemented strains. In
      contrast, the urease-deficient mutant exhibited impaired in vitro growth compared
      to the WT and complemented strains when urea was the sole source of nitrogen.
      Substantial amounts of ammonia were produced by the WT and complemented strains,
      but not with the urease-deficient mutant, which represents the actual nitrogen
      source for mycobacterial growth. However, the urease-deficient mutant displayed
      parental colonization profiles in the lungs, spleen, and liver in mice. Together,
      our data demonstrate a role for the urease activity in M. tuberculosis nitrogen
      metabolism that could be crucial for the pathogen's survival in nutrient-limited
      microenvironments where urea is the sole nitrogen source. Our work supports the
      notion that M. tuberculosis virulence correlates with its unique metabolic
      versatility and ability to utilize virtually any carbon and nitrogen sources
      available in its environment.

PMID- 22645286
TI  - Legionella pneumophila pathogenesis in the Galleria mellonella infection model.
AB  - Legionella pneumophila is a facultative intracellular human pathogen and the
      etiological agent of severe pneumonia known as Legionnaires' disease. Its
      virulence depends on protein secretion systems, in particular, the Dot/Icm type
      IV secretion system (T4SS), which is essential to establish a replication
      permissive vacuole in macrophages. The analysis of the role of these systems and
      their substrates for pathogenesis requires easy-to-use models which approximate
      human infection. We examined the effectiveness of the larvae of the wax moth
      Galleria mellonella as a new model for L. pneumophila infection. We found that
      the L. pneumophila strains 130b, Paris, and JR32 caused mortality of the G.
      mellonella larvae that was strain, infectious dose, growth phase, and T4SS
      dependent. Wild-type L. pneumophila persisted and replicated within the larvae,
      whereas T4SS mutants were rapidly cleared. L. pneumophila strain Lp02, which is
      attenuated in the absence of thymidine but has a functional T4SS, resisted
      clearance in G. mellonella up to 18 h postinfection without inducing mortality.
      Immunofluorescence and transmission electron microscopy revealed that L.
      pneumophila resided within insect hemocytes in a vacuole that ultrastructurally
      resembled the Legionella-containing vacuole (LCV) observed in macrophages. The
      vacuole was decorated with the T4SS effector and LCV marker SidC. Infection
      caused severe damage to the insect organs and triggered immune responses,
      including activation of the phenoloxidase cascade leading to melanization, nodule
      formation, and upregulation of antimicrobial peptides. Taken together, these
      results suggest that G. mellonella provides an effective model to investigate the
      interaction between L. pneumophila and the host.

PMID- 22645288
TI  - Lichen planus pemphigoides in a child.

PMID- 22645287
TI  - Identification of Coli Surface Antigen 23, a novel adhesin of enterotoxigenic
      Escherichia coli.
AB  - Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea, mainly
      in developing countries. Although there are 25 different ETEC adhesins described
      in strains affecting humans, between 15% and 50% of the clinical isolates from
      different geographical regions are negative for these adhesins, suggesting that
      additional unidentified adhesion determinants might be present. Here, we report
      the discovery of Coli Surface Antigen 23 (CS23), a novel adhesin expressed by an
      ETEC serogroup O4 strain (ETEC 1766a), which was negative for the previously
      known ETEC adhesins, albeit it has the ability to adhere to Caco-2 cells. CS23 is
      encoded by an 8.8-kb locus which contains 9 open reading frames (ORFs), 7 of them
      sharing significant identity with genes required for assembly of K88-related
      fimbriae. This gene locus, named aal (adhesion-associated locus), is required for
      the adhesion ability of ETEC 1766a and was able to confer this adhesive phenotype
      to a nonadherent E. coli HB101 strain. The CS23 major structural subunit, AalE,
      shares limited identity with known pilin proteins, and it is more closely related
      to the CS13 pilin protein CshE, carried by human ETEC strains. Our data indicate
      that CS23 is a new member of the diverse adhesin repertoire used by ETEC strains.

PMID- 22645289
TI  - Optimization of sample pretreatment methods for simultaneous determination of
      dolasetron and hydrodolasetron in human plasma by HPLC-ESI-MS.
AB  - A high-performance liquid chromatographic method coupled with electrospray mass
      spectrometry was developed for the simultaneous determination of dolasetron and
      its major metabolite, hydrodolasetron, in human plasma. A new sample pretreatment
      method, i.e., salt induced phase separation extraction (SIPSE), was proposed and
      compared with four other methods, i.e., albumin precipitation, liquid-liquid
      extraction, hydrophobic solvent-induced phase separation extraction and subzero
      temperature induced phase separation extraction. Among these methods, SIPSE
      showed the highest extraction efficiency and the lowest matrix interferences. The
      extraction recoveries obtained from the SIPSE method were all more than 96% for
      dolasetron, hydrodolasetron and ondansetron (internal standard). The SIPSE method
      is also very fast and easy because protein precipitation, analyte extraction and
      sample cleanup are combined into one simple process by mixing acetonitrile with
      plasma and partitioning with 2 mol/L sodium carbonate aqueous solution. The
      correlation coefficients of the calibration curves were all more than 0.997, in
      the range of 7.9-4750.0 ng/mL and 4.8-2855.1 ng/mL for dolasetron and
      hydrodolasetron, respectively. The limits of quantification were 7.9 and 4.8
      ng/mL for dolasetron and hydrodolasetron, respectively. The intra-day and inter
      day repeatability were all less than 10%. The method was successfully applied to
      the pharmacokinetic study of dolasetron.

PMID- 22645290
TI  - White sponge nevus caused by a missense mutation in the keratin 4 gene.

PMID- 22645291
TI  - Genetics and cardiovascular disease: a policy statement from the American Heart
      Association.

PMID- 22645292
TI  - Sustained ventricular tachycardia and ventricular fibrillation complicating non
      ST-segment-elevation acute coronary syndromes.
AB  - BACKGROUND: Ventricular arrhythmias remain a lethal complication of acute
      coronary syndromes (ACS). However, the incidence and prognosis of sustained
      ventricular tachycardia/ventricular fibrillation (VT/VF) in contemporary non-ST
      segment-elevation (NSTE) ACS populations are not well described. METHODS AND
      RESULTS: We examined the incidence of VT/VF and subsequent survival among 9211
      patients enrolled in the Early Glycoprotein IIb/IIIa Inhibition in NSTE ACS
      (EARLY ACS) trial. The cumulative incidence of VT/VF was 1.5% (n=141); 0.6%
      (n=55) had VT/VF <=48 hours after enrollment, and 0.9% (n=86) had VT/VF >48 hours
      after enrollment. Patients with VT/VF more frequently had prior heart failure, an
      ejection fraction <30%, and triple-vessel coronary artery disease. Predictors of
      sustained VT/VF were similar regardless of the timing of VT/VF (<=48 versus >48
      hours). Patients with VT/VF <=48 hours after enrollment had higher 30-day
      mortality than those who did not have VT/VF <=48 hours (13.0% versus 2.2%;
      adjusted odds ratio, 6.73; 95% confidence interval, 2.68-16.9). The increased
      risk of death associated with VT/VF <=48 hours persisted at 1 year. The risk of
      mortality, relative to patients without VT/VF, was greater for patients with
      VT/VF >48 hours (hazard ratio, 20.70; 95% confidence interval, 15.39-27.85) than
      for those with earlier VT/VF (hazard ratio, 7.45; 95% confidence interval, 4.60
      12.08; P=0.0003). The frequency of arrhythmic death was higher in patients with
      VT/VF than in those without VT/VF (26.4% versus 6.9%). CONCLUSIONS: Sustained
      VT/VF is infrequent after NSTE ACS but is as likely to occur after 48 hours as
      within the first 48 hours. The marked increase in all-cause death among NSTE ACS
      patients with both early and late sustained VT/VF raises important considerations
      for aggressive monitoring beyond 48 hours and interventions to prevent arrhythmic
      death in these patients. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00089895.

PMID- 22645293
TI  - Transcatheter aortic valve implantation in situs inversus totalis.
AB  - A frail 84-year old lady with situs inversus totalis and symptomatic aortic
      stenosis underwent a successful transcatheter aortic valve implantation (TAVI)
      after extensive diagnostic work-up. We show illustrative pre- and
      postintervention three-dimensional reconstruction imaging and describe how
      conventional and dedicated imaging software can support the planning and
      performance of TAVI.

PMID- 22645294
TI  - A fluorodeoxyglucose avid mediastinal parathyroid adenoma masquerading as
      metastatic bladder cancer.
AB  - A 64-year old male with a prior medical history of bladder transitional cell
      carcinoma treated with a cystoprostatectomy and adjuvant platinum-based
      chemotherapy 10 years earlier underwent a surveillance positron emission
      tomography (PET) scan that revealed a metabolically active 2-cm nodule in the
      superior mediastinum, anterior to the origin of the innominate artery. The lesion
      was removed due to concerns of metastatic disease using a cervical
      mediastinoscope. Final pathology revealed an ectopic mediastinal parathyroid
      adenoma. The combination of the rare presentation, uncommon surgical approach and
      pathology makes this case unique.

PMID- 22645295
TI  - Successful surgical treatment of a gigantic congenital coronary artery fistula
      immediately after birth.
AB  - A foetus was prenatally diagnosed with a gigantic (12 mm) coronary artery fistula
      (CAF) from the left anterior descending (LAD) coronary artery to right
      ventricular apex at 38 weeks of gestation. LAD was dilated to 10 mm with partial
      aneurysmal changes. Because of concern for sudden ischaemic cardiogenic shock
      soon after birth, the child was electively delivered by caesarean section, with
      surgical fistula closure subsequently performed 1 h after birth. We also highly
      suspected the presence of a clinically significant accessory diagonal branch just
      around the fistula, thus direct fistula closure from outside the heart without
      cardiopulmonary bypass was abandoned and cardiopulmonary bypass was initiated.
      The terminal end of LAD was carefully opened, and the fistula was directly closed
      with four pairs of 6-0 polypropylene mattress sutures under cardioplegic arrest,
      while the opened terminal end of LAD was also repaired with plegetted 6-0
      polypropylene mattress and over-and-over sutures. After 4 days of post-surgical
      extracorporeal life support for over-systemic pulmonary hypertension, the patient
      recovered without complications. Although postoperative echocardiography 5 months
      after the operation showed normal cardiac function without ventricular asynergy,
      the dilated and aneurysmal LAD remained unchanged.

PMID- 22645296
TI  - Relationship between intraprostatic tracer deposits and sentinel lymph node
      mapping in prostate cancer patients.
AB  - Intraprostatic injection of the hybrid tracer indocyanine green (ICG)-(99m)Tc
      nanocolloid enables both preoperative sentinel node (SN) identification and
      intraoperative visualization of the SN. Relating the fluorescence deposits in
      embedded prostate tissue specimens to the preoperatively detected SNs also
      provides the opportunity to study the influence of their placement on lymphatic
      drainage pattern. METHODS: Nineteen patients with prostate carcinoma scheduled
      for robot-assisted laparoscopic prostatectomy and lymph node (LN) dissection were
      included. ICG-(99m)Tc-nanocolloid was injected intraprostatically, guided by
      ultrasound. SN biopsy was performed using a combination of radioguidance and
      fluorescence guidance. Tracer distribution was visualized in paraffin-embedded
      prostate samples using ex vivo fluorescence imaging. This distribution was
      correlated to the number and location of the SNs identified on preoperative
      lymphoscintigraphy and SPECT/CT. RESULTS: ICG-(99m)Tc-nanocolloid helped guide
      surgical excision of the SNs. Ex vivo fluorescence imaging revealed a large
      variation in the locations of intraprostatic tracer deposits among patients.
      Tracer deposits in the peripheral zone correlated with a higher number of
      visualized LNs than deposits in the central zone (on average, 4.7 vs. 2.4 LNs per
      patient). Furthermore, tracer deposits in the mid gland correlated with a higher
      number of visualized LNs than deposits near the base or apex of the prostate (on
      average, 6 vs. 3.5 LNs per patient). CONCLUSION: The hybrid nature of the tracer
      not only enables surgical guidance but also provides an opportunity to study the
      correlation between the location of tracer deposits within the prostate and the
      number and location of preoperatively visualized SNs. These data suggest that the
      location at which a tracer deposit is placed influences the lymphatic drainage
      pattern.

PMID- 22645297
TI  - Comparing the hybrid fluorescent-radioactive tracer indocyanine green-99mTc
      nanocolloid with 99mTc-nanocolloid for sentinel node identification: a validation
      study using lymphoscintigraphy and SPECT/CT.
AB  - The purpose of this study was to compare the lymphoscintigraphic drainage
      patterns of a hybrid sentinel node tracer consisting of the fluorescent dye
      indocyanine green (ICG) and (99m)Tc-nanocolloid with the drainage pattern of
      (99m)Tc-nanocolloid alone, the current standard tracer in many European
      countries. METHODS: Twenty-five patients with a melanoma in the head and neck
      region (n = 10), a melanoma on the trunk (n = 6), or penile carcinoma (n = 9) who
      were scheduled for sentinel node biopsy were prospectively included. First, the
      standard (99m)Tc-nanocolloid procedure was performed. After injection at the
      lesion site, lymphoscintigraphy was performed with a 10-min dynamic study and
      static planar images at 10 min and 2 h after injection, followed by SPECT/CT. The
      same scintigraphic procedure was repeated after injection of hybrid ICG-(99m)Tc
      nanocolloid the same afternoon in 10 patients or the next morning in 15 patients.
      The paired images of both injections were evaluated, and count rates in the
      sentinel nodes were calculated and compared. Sentinel nodes were surgically
      localized using blue dye, a gamma-ray detection probe, a portable gamma-camera,
      and a fluorescence camera. RESULTS: Lymphatic drainage was visualized in all 25
      patients using (99m)Tc-nanocolloid, leading to the identification of 66 sentinel
      nodes in total. These same sentinel nodes were also identified during the second
      scintigraphic procedure with ICG-(99m)Tc-nanocolloid. Moreover, a high
      correlation between the radioactive counting rates in the sentinel nodes of both
      scintigraphic studies was observed (mean R(2) = 0.83). Intraoperatively (4-23 h
      after the second injection), all preoperatively identified sentinel nodes could
      be localized using radio- and fluorescence guidance combined. In total, 95% of
      the sentinel nodes could be intraoperatively visualized by means of fluorescence
      imaging, whereas merely 54% stained blue. Ex vivo, all radioactive sentinel nodes
      were fluorescent and vice versa. No adverse reactions were observed. CONCLUSION:
      The lymphatic drainage pattern of ICG-(99m)Tc-nanocolloid is identical to that of
      (99m)Tc-nanocolloid. This observation, together with the added value of
      intraoperative fluorescence guidance, warrants wider evaluation of hybrid ICG
      (99m)Tc-nanocolloid as a tracer for sentinel node procedures.

PMID- 22645298
TI  - Assessment of treatment response in patients with glioblastoma using O-(2-18F
      fluoroethyl)-L-tyrosine PET in comparison to MRI.
AB  - The assessment of treatment response in glioblastoma is difficult with MRI
      because reactive blood-brain barrier alterations with contrast enhancement can
      mimic tumor progression. In this study, we investigated the predictive value of
      PET using O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET PET) during treatment.
      METHODS: In a prospective study, 25 patients with glioblastoma were investigated
      by MRI and (18)F-FET PET after surgery (MRI-/FET-1), early (7-10 d) after
      completion of radiochemotherapy with temozolomide (RCX) (MRI-/FET-2), and 6-8 wk
      later (MRI-/FET-3). Maximum and mean tumor-to-brain ratios (TBR(max) and
      TBR(mean), respectively) were determined by region-of-interest analyses.
      Furthermore, gadolinium contrast-enhancement volumes on MRI (Gd-volume) and tumor
      volumes in (18)F-FET PET images with a tumor-to-brain ratio greater than 1.6
      (T(vol 1.6)) were calculated using threshold-based volume-of-interest analyses.
      The patients were grouped into responders and nonresponders according to the
      changes of these parameters at different cutoffs, and the influence on
      progression-free survival and overall survival was tested using univariate and
      multivariate survival analyses and by receiver-operating-characteristic analyses.
      RESULTS: Early after completion of RCX, a decrease of both TBR(max) and TBR(mean)
      was a highly significant and independent statistical predictor for progression
      free survival and overall survival. Receiver-operating-characteristic analysis
      showed that a decrease of the TBR(max) between FET-1 and FET-2 of more than 20%
      predicted favorable survival [corrected], with a sensitivity of 83% and a
      specificity of 67% (area under the curve, 0.75). Six to eight weeks later, the
      predictive value of TBR(max) and TBR(mean) was less significant, but an
      association between a decrease of T(vol 1.6) and PFS was noted. In contrast, Gd
      volume changes had no significant predictive value for survival. CONCLUSION: In
      contrast to Gd-volumes on MRI, changes in (18)F-FET PET may be a valuable
      parameter to assess treatment response in glioblastoma and to predict survival
      time.

PMID- 22645299
TI  - The expression of translocator protein in human thyroid cancer and its role in
      the response of thyroid cancer cells to oxidative stress.
AB  - The translocator protein (TSPO), formerly known as a peripheral benzodiazepine
      receptor, exerts pro-apoptotic function via regulation of mitochondrial membrane
      potential. We examined TSPO expression in human thyroid tumors (25 follicular
      adenomas (FA), 15 follicular cancers (FC), and 70 papillary cancers (PC)). The
      role of TSPO in the regulation of cell growth, migration, and apoptosis was
      examined in thyroid cancer cell lines after TSPO knockdown with siRNA and after
      treatment with TSPO antagonist (PK11195). Compared with normal thyroid, the level
      of TSPO expression was increased in FA, FC, and PC in 24, 26.6, and 55.7% of
      cases respectively. Thyroid cancer cell lines demonstrated variable levels of
      TSPO expression, without specific association with thyroid oncogene mutations.
      Treatment with inhibitors of PI3K/AKT or MEK/ERK signaling was not associated
      with changes in TSPO expression. Treatment with histone deacetylase inhibitor
      (valproic acid) increased TSPO expression in TSPO-deficient cell lines (FTC236
      cells). TSPO gene silencing or treatment with PK11195 did not affect thyroid
      cancer cell growth and migration but prevented depolarization of mitochondrial
      membranes induced by oxidative stress. Induction of TSPO expression by valproic
      acid was associated with increased sensitivity of FTC236 to oxidative stress
      inducible apoptosis. Overall, we showed that TSPO expression is frequently
      increased in PC. In vitro data suggested the role of epigenetic mechanism(s) in
      the regulation of TSPO in thyroid cells. Implication of TSPO in the thyroid
      cancer cell response to oxidative stress suggested its potential role in the
      regulation of thyroid cancer cell response to treatment with radioiodine and
      warrants further investigation.

PMID- 22645300
TI  - Expression of the proteoglycan syndecan-4 and the mechanism by which it mediates
      stress fiber formation in folliculostellate cells in the rat anterior pituitary
      gland.
AB  - Folliculostellate (FS) cells in the anterior pituitary gland appear to have
      multifunctional properties. FS cells connect to each other at gap junctions and
      thereby form a histological and functional network. We have performed a series of
      studies on network formation in FS cells and recently reported that FS cells
      markedly prolong their cytoplasmic processes and form numerous interconnections
      with neighboring FS cells in the presence of laminin, an extracellular matrix
      (ECM) component of the basement membrane. In this study, we investigated the
      mechanism of this extension of FS cell cytoplasmic processes under the influence
      of laminin and found that laminin promoted stress fiber formation within FS
      cells. Next, we noted that formation of stress fibers in FS cells was mediated by
      syndecan-4, a transmembrane proteoglycan that binds ECM and soluble factors via
      their extracellular glycosaminoglycan chain. We then observed that expressions of
      syndecan-4 and alpha-actinin (a microfilament bundling protein that cross-links
      actin stress fibers in FS cells) were upregulated by laminin. Using specific
      siRNA of syndecan-4, actin polymerization of FS cells was inhibited. Our findings
      suggest that FS cells received a signal from laminin-syndecan-4 interaction,
      which resulted in morphological changes, and that the formation of a
      morphological and functional network in FS cells was transduced by a syndecan-4
      dependent mechanism in the presence of ECM.

PMID- 22645301
TI  - Role of testosterone and photoperiod on seasonal changes in horn growth and sperm
      variables in the Iberian ibex: a model for polygynous wild bovids.
AB  - This work examines the effect of testosterone secretion and photoperiod on
      seasonal changes in horn growth and sperm variables in the Iberian ibex (Capra
      pyrenaica), here used as a model for polygynous wild bovids. The hypothesis that
      high levels of testosterone provide an endocrine signal that inhibits horn growth
      in autumn was tested by assessing the effect of cyproterone acetate (CA), an anti
      androgen, administered in October - coinciding with the period of natural
      increases in plasma testosterone concentrations - under different photoperiodic
      conditions (natural photoperiod and artificial long days). The persistence of
      horn growth during autumn in all ibexes held under the long-day photoperiodic
      conditions clearly shows that horn growth regulation in the mating season is
      primarily modulated by day length and not by a fall in testosterone
      concentration. A retrospectively designed second experiment involving
      testosterone propionate (TP) administration in April (when horns are growing) was
      then undertaken to confirm that high levels of testosterone do not inhibit horn
      growth. Overall, the results strongly suggest that the rise in testosterone
      secretion during the autumn mating season does not act as an endocrine signal for
      the arrest of horn growth, although the rate of horn growth before the mating
      season may be related to springtime testosterone levels. A direct relationship
      was seen between the rate of horn growth and the incidence of sperm
      abnormalities. Neither CA treatment in October nor TP administration in April
      affected the studied sperm variables. By contrast, CA treatment plus artificial
      long days in autumn had a negative effect on sperm motility and sperm morphology.

PMID- 22645302
TI  - Dynamic change of chromatin conformation in response to hypoxia enhances the
      expression of GLUT3 (SLC2A3) by cooperative interaction of hypoxia-inducible
      factor 1 and KDM3A.
AB  - Hypoxia-inducible factor 1 (HIF1) is a master regulator of adaptive gene
      expression under hypoxia. However, a role for HIF1 in the epigenetic regulation
      remains unknown. Genome-wide analysis of HIF1 binding sites (chromatin
      immunoprecipitation [ChIP] with deep sequencing) of endothelial cells clarified
      that HIF1 mainly binds to the intergenic regions distal from transcriptional
      starting sites under both normoxia and hypoxia. Next, we examined the temporal
      profile of gene expression under hypoxic conditions by using DNA microarrays. We
      clarified that early hypoxia-responsive genes are functionally associated with
      glycolysis, including GLUT3 (SLC2A3). Acetylated lysine 27 of histone 3 covered
      the HIF1 binding sites, and HIF1 functioned as an enhancer of SLC2A3 by
      interaction with lysine (K)-specific demethylase 3A (KDM3A). Knockdown of
      HIF1alpha and KDM3A showed that glycolytic genes are regulated by both HIF1 and
      KDM3A and respond to hypoxia in a manner independent of cell type specificity. We
      elucidated that both the chromatin conformational structure and histone
      modification change under hypoxic conditions and enhance the expression of SLC2A3
      based on the combined results of chromatin conformation capture (3C) and ChIP
      assays. KDM3A is recruited to the SLC2A3 locus in an HIF1-dependent manner and
      demethylates H3K9me2 so as to upregulate its expression. These findings provide
      novel insights into the interaction between HIF1 and KDM3A and also the
      epigenetic regulation of HIF1.

PMID- 22645303
TI  - Claudin-2 promotes breast cancer liver metastasis by facilitating tumor cell
      interactions with hepatocytes.
AB  - We previously identified claudin-2 as a functional mediator of breast cancer
      liver metastasis. We now confirm that claudin-2 levels are elevated in liver
      metastases, but not in skin metastases, compared to levels in their matched
      primary tumors in patients with breast cancer. Moreover, claudin-2 is
      specifically expressed in liver-metastatic breast cancer cells compared to
      populations derived from bone or lung metastases. The increased liver tropism
      exhibited by claudin-2-expressing breast cancer cells requires claudin-2-mediated
      interactions between breast cancer cells and primary hepatocytes. Furthermore,
      the reduction of the claudin-2 expression level, either in cancer cells or in
      primary hepatocytes, diminishes these heterotypic cell-cell interactions.
      Finally, we demonstrate that the first claudin-2 extracellular loop is essential
      for mediating tumor cell-hepatocyte interactions and the ability of breast cancer
      cells to form liver metastases in vivo. Thus, during breast cancer liver
      metastasis, claudin-2 shifts from acting within tight-junctional complexes to
      functioning as an adhesion molecule between breast cancer cells and hepatocytes.

PMID- 22645304
TI  - Evidence for DNA-binding domain--ligand-binding domain communications in the
      androgen receptor.
AB  - DNA binding as well as ligand binding by nuclear receptors has been studied
      extensively. Both binding functions are attributed to isolated domains of which
      the structure is known. The crystal structure of a complete receptor in complex
      with its ligand and DNA-response element, however, has been solved only for the
      peroxisome proliferator-activated receptor gamma (PPARgamma)-retinoid X receptor
      alpha (RXRalpha) heterodimer. This structure provided the first indication of
      direct interactions between the DNA-binding domain (DBD) and ligand-binding
      domain (LBD). In this study, we investigated whether there is a similar interface
      between the DNA- and ligand-binding domains for the androgen receptor (AR).
      Despite the structural differences between the AR- and PPARgamma-LBD, a
      combination of in silico modeling and docking pointed out a putative interface
      between AR-DBD and AR-LBD. The surfaces were subjected to a point mutation
      analysis, which was inspired by known AR mutations described in androgen
      insensitivity syndromes and prostate cancer. Surprisingly, AR-LBD mutations
      D695N, R710A, F754S, and P766A induced a decrease in DNA binding but left ligand
      binding unaffected, while the DBD-residing mutations K590A, K592A, and E621A
      lowered the ligand-binding but not the DNA-binding affinity. We therefore propose
      that these residues are involved in allosteric communications between the AR-DBD
      and AR-LBD.

PMID- 22645305
TI  - GDP-mannose-4,6-dehydratase is a cytosolic partner of tankyrase 1 that inhibits
      its poly(ADP-ribose) polymerase activity.
AB  - Tankyrase 1 is a poly(ADP-ribose) polymerase (PARP) that participates in a broad
      range of cellular activities due to interaction with multiple binding partners.
      Tankyrase 1 recognizes a linear six-amino-acid degenerate motif and, hence, has
      hundreds of potential target proteins. Binding of partner proteins to tankyrase 1
      usually results in their poly(ADP-ribosyl)ation (PARsylation) and can lead to
      ubiquitylation and proteasomal degradation. However, it is not known how
      tankyrase 1 PARP activity is regulated. Here we identify GDP-mannose 4,6
      dehydratase (GMD) as a binding partner of tankyrase 1. GMD is a cytosolic protein
      required for the first step of fucose synthesis. We show that GMD is complexed to
      tankyrase 1 in the cytosol throughout interphase, but its association with
      tankyrase 1 is reduced upon entry into mitosis, when tankyrase 1 binds to its
      other partners TRF1 (at telomeres) and NuMA (at spindle poles). In contrast to
      other binding partners, GMD is not PARsylated by tankyrase 1. Indeed, we show
      that GMD inhibits tankyrase 1 PARP activity in vitro, dependent on the GMD
      tankyrase 1 binding motif. In vivo, depletion of GMD led to degradation of
      tankyrase 1, dependent on the catalytic PARP activity of tankyrase 1. We
      speculate that association of tankyrase 1 with GMD in the cytosol sequesters
      tankyrase 1 in an inactive stable form that can be tapped by other target
      proteins as needed.

PMID- 22645306
TI  - RMI1 promotes DNA replication fork progression and recovery from replication fork
      stress.
AB  - RMI1 is a member of an evolutionarily conserved complex composed of BLM and
      topoisomerase IIIalpha (TopoIIIalpha). This complex exhibits strand passage
      activity in vitro, which is likely important for DNA repair and DNA replication
      in vivo. The inactivation of RMI1 causes genome instability, including elevated
      levels of sister chromatid exchange and accelerated tumorigenesis. Using
      molecular combing to analyze DNA replication at the single-molecule level, we
      show that RMI1 is required to promote normal replication fork progression. The
      fork progression defect in RMI1-depleted cells is alleviated in cells lacking
      BLM, indicating that RMI1 functions downstream of BLM in promoting replication
      elongation. RMI1 localizes to subnuclear foci with BLM and TopoIIIalpha in
      response to replication stress. The proper localization of the complex requires a
      BLM-TopoIIIalpha-RMI1 interaction and is essential for RMI1 to promote recovery
      from replication stress. These findings reveal direct roles of RMI1 in DNA
      replication and the replication stress response, which could explain the
      molecular basis for its involvement in suppressing sister chromatid exchange and
      tumorigenesis.

PMID- 22645307
TI  - STIM1-Ca(2+) signaling is required for the hypertrophic growth of skeletal muscle
      in mice.
AB  - Immediately after birth, skeletal muscle must undergo an enormous period of
      growth and differentiation that is coordinated by several intertwined growth
      signaling pathways. How these pathways are integrated remains unclear but is
      likely to involve skeletal muscle contractile activity and calcium (Ca(2+))
      signaling. Here, we show that Ca(2+) signaling governed by stromal interaction
      molecule 1 (STIM1) plays a central role in the integration of signaling and,
      therefore, muscle growth and differentiation. Conditional deletion of STIM1 from
      the skeletal muscle of mice (mSTIM1(-/-) mice) leads to profound growth delay,
      reduced myonuclear proliferation, and perinatal lethality. We show that muscle
      fibers of neonatal mSTIM1(-/-) mice cannot support the activity-dependent Ca(2+)
      transients evoked by tonic neurostimulation, even though excitation contraction
      coupling (ECC) remains unperturbed. In addition, disruption of tonic Ca(2+)
      signaling in muscle fibers attenuates downstream muscle growth signaling, such as
      that of calcineurin, mitogen-activated protein (MAP) kinases, extracellular
      signal-regulated kinase 1 and 2 (ERK1/2), and AKT. Based on our findings, we
      propose a model wherein STIM1-mediated store-operated calcium entry (SOCE)
      governs the Ca(2+) signaling required for cellular processes that are necessary
      for neonatal muscle growth and differentiation.

PMID- 22645308
TI  - Mus81-Mms4 functions as a single heterodimer to cleave nicked intermediates in
      recombinational DNA repair.
AB  - The formation of crossovers is a fundamental genetic process. The XPF-family
      endonuclease Mus81-Mms4 (Eme1) contributes significantly to crossing over in
      eukaryotes. A key question is whether Mus81-Mms4 can process Holliday junctions
      that contain four uninterrupted strands. Holliday junction cleavage requires the
      coordination of two active sites, necessitating the assembly of two Mus81-Mms4
      heterodimers. Contrary to this expectation, we show that Saccharomyces cerevisiae
      Mus81-Mms4 exists as a single heterodimer both in solution and when bound to DNA
      substrates in vitro. Consistently, immunoprecipitation experiments demonstrate
      that Mus81-Mms4 does not multimerize in vivo. Moreover, chromatin-bound Mus81
      Mms4 does not detectably form higher-order multimers. We show that Cdc5 kinase
      activates Mus81-Mms4 nuclease activity on 3' flaps and Holliday junctions in
      vitro but that activation does not induce a preference for Holliday junctions and
      does not induce multimerization of the Mus81-Mms4 heterodimer. These data support
      a model in which Mus81-Mms4 cleaves nicked recombination intermediates such as
      displacement loops (D-loops), nicked Holliday junctions, or 3' flaps but not
      intact Holliday junctions with four uninterrupted strands. We infer that Mus81
      dependent crossing over occurs in a noncanonical manner that does not involve the
      coordinated cleavage of classic Holliday junctions.

PMID- 22645309
TI  - Maintenance of very long telomeres by recombination in the Kluyveromyces lactis
      stn1-M1 mutant involves extreme telomeric turnover, telomeric circles, and
      concerted telomeric amplification.
AB  - Some cancers utilize the recombination-dependent process of alternative
      lengthening of telomeres (ALT) to maintain long heterogeneous telomeres. Here, we
      studied the recombinational telomere elongation (RTE) of the Kluyveromyces lactis
      stn1-M1 mutant. We found that the total amount of the abundant telomeric DNA in
      stn1-M1 cells is subject to rapid variation and that it is likely to be primarily
      extrachromosomal. Rad50 and Rad51, known to be required for different RTE
      pathways in Saccharomyces cerevisiae, were not essential for the production of
      either long telomeres or telomeric circles in stn1-M1 cells. Circles of DNA
      containing telomeric repeats (t-circles) either present at the point of
      establishment of long telomeres or introduced later into stn1-M1 cells each led
      to the formation of long tandem arrays of the t-circle's sequence, which were
      incorporated at multiple telomeres. These tandem arrays were extraordinarily
      unstable and showed evidence of repeated rounds of concerted amplification. Our
      results suggest that the maintenance of telomeres in the stn1-M1 mutant involves
      extreme turnover of telomeric sequences from processes including both large
      deletions and the copying of t-circles.

PMID- 22645310
TI  - Prolyl isomerase Pin1 regulates neuronal differentiation via beta-catenin.
AB  - The Wnt/beta-catenin pathway promotes proliferation of neural progenitor cells
      (NPCs) at early stages and induces neuronal differentiation from NPCs at late
      stages, but the molecular mechanisms that control this stage-specific response
      are unclear. Pin1 is a prolyl isomerase that regulates cell signaling uniquely by
      controlling protein conformation after phosphorylation, but its role in neuronal
      differentiation is not known. Here we found that whereas Pin1 depletion
      suppresses neuronal differentiation, Pin1 overexpression enhances it, without any
      effects on gliogenesis from NPCs in vitro. Consequently, Pin1-null mice have
      significantly fewer upper layer neurons in the motor cortex and severely impaired
      motor activity during the neonatal stage. A proteomic approach identified beta
      catenin as a major substrate for Pin1 in NPCs, in which Pin1 stabilizes beta
      catenin. As a result, Pin1 knockout leads to reduced beta-catenin during
      differentiation but not proliferation of NPCs in developing brains. Importantly,
      defective neuronal differentiation in Pin1 knockout NPCs is fully rescued in
      vitro by overexpression of beta-catenin but not a beta-catenin mutant that fails
      to act as a Pin1 substrate. These results show that Pin1 is a novel regulator of
      NPC differentiation by acting on beta-catenin and provides a new
      postphosphorylation signaling mechanism to regulate developmental stage-specific
      functioning of beta-catenin signaling in neuronal differentiation.

PMID- 22645311
TI  - Cells lacking the fumarase tumor suppressor are protected from apoptosis through
      a hypoxia-inducible factor-independent, AMPK-dependent mechanism.
AB  - Loss-of-function mutations of the tumor suppressor gene encoding fumarase (FH)
      occur in individuals with hereditary leiomyomatosis and renal cell cancer
      syndrome (HLRCC). We found that loss of FH activity conferred protection from
      apoptosis in normal human renal cells and fibroblasts. In FH-defective cells,
      both hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha accumulated, but
      they were not required for apoptosis protection. Conversely, AMP-activated
      protein kinase (AMPK) was activated and required, as evidenced by the finding
      that FH inactivation failed to protect AMPK-null mouse embryo fibroblasts (MEFs)
      and AMPK-depleted human renal cells. Activated AMPK was detected in renal cysts,
      which occur in mice with kidney-targeted deletion of Fh1 and in kidney cancers of
      HLRCC patients. In Fh1-null MEFs, AMPK activation was sustained by fumarate
      accumulation and not by defective energy metabolism. Addition of fumarate and
      succinate to kidney cells led to extracellular signal-regulated kinase 1/2
      (ERK1/2) and AMPK activation, probably through a receptor-mediated mechanism.
      These findings reveal a new mechanism of tumorigenesis due to FH loss and an
      unexpected pro-oncogenic role for AMPK that is important in considering AMPK
      reactivation as a therapeutic strategy against cancer.

PMID- 22645312
TI  - Histone methyltransferase NSD2/MMSET mediates constitutive NF-kappaB signaling
      for cancer cell proliferation, survival, and tumor growth via a feed-forward
      loop.
AB  - Constitutive NF-kappaB activation by proinflammatory cytokines plays a major role
      in cancer progression. However, the underlying mechanism is still unclear. We
      report here that histone methyltransferase NSD2 (also known as MMSET or WHSC1), a
      target of bromodomain protein ANCCA/ATAD2, acts as a strong coactivator of NF
      kappaB by directly interacting with NF-kappaB for activation of target genes,
      including those for interleukin-6 (IL-6), IL-8, vascular endothelial growth
      factor A (VEGFA), cyclin D, Bcl-2, and survivin, in castration-resistant prostate
      cancer (CRPC) cells. NSD2 is recruited to the target gene promoters upon
      induction and mediates NF-kappaB activation-associated elevation of histone
      H3K36me2 and H3K36me3 marks at the promoter, which involves its methylase
      activity. Interestingly, we found that NSD2 is also critical for cytokine-induced
      recruitment of NF-kappaB and acetyltransferase p300 and histone hyperacetylation.
      Importantly, NSD2 is overexpressed in prostate cancer tumors, and its
      overexpression correlates with NF-kappaB activation. Furthermore, NSD2 expression
      is strongly induced by tumor necrosis factor alpha (TNF-alpha) and IL-6 via NF
      kappaB and plays a crucial role in tumor growth. These results identify NSD2 to
      be a key chromatin regulator of NF-kappaB and mediator of the cytokine autocrine
      loop for constitutive NF-kappaB activation and emphasize the important roles
      played by NSD2 in cancer cell proliferation and survival and tumor growth.

PMID- 22645314
TI  - Dynamic association of ORCA with prereplicative complex components regulates DNA
      replication initiation.
AB  - In eukaryotes, initiation of DNA replication requires the assembly of a
      multiprotein prereplicative complex (pre-RC) at the origins. We recently reported
      that a WD repeat-containing protein, origin recognition complex (ORC)-associated
      (ORCA/LRWD1), plays a crucial role in stabilizing ORC to chromatin. Here, we find
      that ORCA is required for the G(1)-to-S-phase transition in human cells. In
      addition to binding to ORC, ORCA associates with Cdt1 and its inhibitor, geminin.
      Single-molecule pulldown experiments demonstrate that each molecule of ORCA can
      bind to one molecule of ORC, one molecule of Cdt1, and two molecules of geminin.
      Further, ORCA directly interacts with the N terminus of Orc2, and the stability
      of ORCA is dependent on its association with Orc2. ORCA associates with Orc2
      throughout the cell cycle, with Cdt1 during mitosis and G(1), and with geminin in
      post-G(1) cells. Overexpression of geminin results in the loss of interaction
      between ORCA and Cdt1, suggesting that increased levels of geminin in post-G(1)
      cells titrate Cdt1 away from ORCA. We propose that the dynamic association of
      ORCA with pre-RC components modulates the assembly of its interacting partners on
      chromatin and facilitates DNA replication initiation.

PMID- 22645313
TI  - Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes.
AB  - The E6AP ubiquitin ligase catalyzes the high-risk human papillomaviruses' E6
      mediated ubiquitylation of p53, contributing to the neoplastic progression of
      cells infected by these viruses. Defects in the activity and the dosage of E6AP
      are linked to Angelman syndrome and to autism spectrum disorders, respectively,
      highlighting the need for precise control of the enzyme. With the exception of
      HERC2, which modulates the ubiquitin ligase activity of E6AP, little is known
      about the regulation or function of E6AP normally. Using a proteomic approach, we
      have identified and validated several new E6AP-interacting proteins, including
      HIF1AN, NEURL4, and mitogen-activated protein kinase 6 (MAPK6). E6AP exists as
      part of several different protein complexes, including the proteasome and an
      independent high-molecular-weight complex containing HERC2, NEURL4, and MAPK6. In
      examining the functional consequence of its interaction with the proteasome, we
      found that UBE3C (another proteasome-associated ubiquitin ligase), but not E6AP,
      contributes to proteasomal processivity in mammalian cells. We also found that E6
      associates with the HERC2-containing high-molecular-weight complex through its
      binding to E6AP. These proteomic studies reveal a level of complexity for E6AP
      that has not been previously appreciated and identify a number of new cellular
      proteins through which E6AP may be regulated or functioning.

PMID- 22645315
TI  - Phosphatidylinositol-3-kinase C2beta and TRIM27 function to positively and
      negatively regulate IgE receptor activation of mast cells.
AB  - Cross-linking of the IgE receptor (FcepsilonRI) on mast cells plays a critical
      role in IgE-dependent allergy, including allergic rhinitis, asthma, anaphylaxis,
      and immediate-type hypersensitivity reactions. Previous studies have demonstrated
      that the K(+) channel, KCa3.1, plays a critical role in IgE-stimulated Ca(2+)
      entry and degranulation in both human and mouse mast cells. We now have shown
      that the class II phosphatidylinositol-3-kinase C2beta (PI3KC2beta) is necessary
      for FcepsilonRI-stimulated activation of KCa3.1, Ca(2+) influx, cytokine
      production, and degranulation of bone marrow-derived mast cells (BMMC). In
      addition, we found that the E3 ubiquitin ligase, tripartite motif containing
      protein 27 (TRIM27), negatively regulates FcepsilonRI activation of KCa3.1 and
      downstream signaling by ubiquitinating and inhibiting PI3KC2beta. TRIM27(-/-)
      mice are also more susceptible in vivo to acute anaphylaxis. These findings
      identify TRIM27 as an important negative regulator of mast cells in vivo and
      suggest that PI3KC2beta is a potential new pharmacologic target to treat IgE
      mediated disease.

PMID- 22645317
TI  - dbCAN: a web resource for automated carbohydrate-active enzyme annotation.
AB  - Carbohydrate-active enzymes (CAZymes) are very important to the biotech industry,
      particularly the emerging biofuel industry because CAZymes are responsible for
      the synthesis, degradation and modification of all the carbohydrates on Earth. We
      have developed a web resource, dbCAN
      (http://csbl.bmb.uga.edu/dbCAN/annotate.php), to provide a capability for
      automated CAZyme signature domain-based annotation for any given protein data set
      (e.g. proteins from a newly sequenced genome) submitted to our server. To
      accomplish this, we have explicitly defined a signature domain for every CAZyme
      family, derived based on the CDD (conserved domain database) search and
      literature curation. We have also constructed a hidden Markov model to represent
      the signature domain of each CAZyme family. These CAZyme family-specific HMMs are
      our key contribution and the foundation for the automated CAZyme annotation.

PMID- 22645316
TI  - Global identification and characterization of both O-GlcNAcylation and
      phosphorylation at the murine synapse.
AB  - O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic, reversible monosaccharide
      modifier of serine and threonine residues on intracellular protein domains.
      Crosstalk between O-GlcNAcylation and phosphorylation has been hypothesized.
      Here, we identified over 1750 and 16,500 sites of O-GlcNAcylation and
      phosphorylation from murine synaptosomes, respectively. In total, 135 (7%) of all
      O-GlcNAcylation sites were also found to be sites of phosphorylation. Although
      many proteins were extensively phosphorylated and minimally O-GlcNAcylated,
      proteins found to be extensively O-GlcNAcylated were almost always phosphorylated
      to a similar or greater extent, indicating the O-GlcNAcylation system is
      specifically targeting a subset of the proteome that is also phosphorylated. Both
      PTMs usually occur on disordered regions of protein structure, within which, the
      location of O-GlcNAcylation and phosphorylation is virtually random with respect
      to each other, suggesting that negative crosstalk at the structural level is not
      a common phenomenon. As a class, protein kinases are found to be more extensively
      O-GlcNAcylated than proteins in general, indicating the potential for crosstalk
      of phosphorylation with O-GlcNAcylation via regulation of enzymatic activity.

PMID- 22645318
TI  - METAGENassist: a comprehensive web server for comparative metagenomics.
AB  - With recent improvements in DNA sequencing and sample extraction techniques, the
      quantity and quality of metagenomic data are now growing exponentially. This
      abundance of richly annotated metagenomic data and bacterial census information
      has spawned a new branch of microbiology called comparative metagenomics.
      Comparative metagenomics involves the comparison of bacterial populations between
      different environmental samples, different culture conditions or different
      microbial hosts. However, in order to do comparative metagenomics, one typically
      requires a sophisticated knowledge of multivariate statistics and/or advanced
      software programming skills. To make comparative metagenomics more accessible to
      microbiologists, we have developed a freely accessible, easy-to-use web server
      for comparative metagenomic analysis called METAGENassist. Users can upload their
      bacterial census data from a wide variety of common formats, using either
      amplified 16S rRNA data or shotgun metagenomic data. Metadata concerning
      environmental, culture, or host conditions can also be uploaded. During the data
      upload process, METAGENassist also performs an automated taxonomic-to-phenotypic
      mapping. Phenotypic information covering nearly 20 functional categories such as
      GC content, genome size, oxygen requirements, energy sources and preferred
      temperature range is automatically generated from the taxonomic input data. Using
      this phenotypically enriched data, users can then perform a variety of
      multivariate and univariate data analyses including fold change analysis, t
      tests, PCA, PLS-DA, clustering and classification. To facilitate data processing,
      users are guided through a step-by-step analysis workflow using a variety of
      menus, information hyperlinks and check boxes. METAGENassist also generates
      colorful, publication quality tables and graphs that can be downloaded and used
      directly in the preparation of scientific papers. METAGENassist is available at
      http://www.metagenassist.ca.

PMID- 22645319
TI  - Duplicate gene enrichment and expression pattern diversification in
      multicellularity.
AB  - The enrichment of duplicate genes, and therefore paralogs (proteins coded by
      duplicate genes), in multicellular versus unicellular organisms enhances genomic
      functional innovation. This study quantitatively examined relationships among
      paralog enrichment, expression pattern diversification and multicellularity,
      aiming to better understand genomic basis of multicellularity. Paralog abundance
      in specific cells was compared with those in unicellular proteomes and the whole
      proteomes of multicellular organisms. The budding yeast, Saccharomyces cerevisiae
      and the nematode, Caenorhabditis elegans, for which the gene sets expressed in
      specific cells are available, were used as uni and multicellular models,
      respectively. Paralog count (K) distributions [P((k))] follow a power-law
      relationship [Formula in text] in the whole proteomes of both species and in
      specific C. elegans cells. The value of the constant alpha can be used as a gauge
      of paralog abundance; the higher the value, the lower the paralog abundance. The
      alpha-value is indeed lower in the whole proteome of C. elegans (1.74) than in S.
      cerevisiae (2.34), quantifying the enrichment of paralogs in multicellular
      species. We also found that the power-law relationship applies to the proteomes
      of specific C. elegans cells. Strikingly, values of alpha in specific cells are
      higher and comparable to that in S. cerevisiae. Thus, paralog abundance in
      specific cells is lower and comparable to that in unicellular species.
      Furthermore, how much the expression level of a gene fluctuates across different
      C. elegans cells correlates positively with its paralog count, which is further
      confirmed by human gene-expression patterns across different tissues. Taken
      together, these results quantitatively and mechanistically establish enrichment
      of paralogs with diversifying expression patterns as genomic and evolutionary
      basis of multicellularity.

PMID- 22645320
TI  - Integrative analysis of gene and miRNA expression profiles with transcription
      factor-miRNA feed-forward loops identifies regulators in human cancers.
AB  - We describe here a novel method for integrating gene and miRNA expression
      profiles in cancer using feed-forward loops (FFLs) consisting of transcription
      factors (TFs), miRNAs and their common target genes. The dChip-GemiNI (Gene and
      miRNA Network-based Integration) method statistically ranks computationally
      predicted FFLs by their explanatory power to account for differential gene and
      miRNA expression between two biological conditions such as normal and cancer.
      GemiNI integrates not only gene and miRNA expression data but also
      computationally derived information about TF-target gene and miRNA-mRNA
      interactions. Literature validation shows that the integrated modeling of
      expression data and FFLs better identifies cancer-related TFs and miRNAs compared
      to existing approaches. We have utilized GemiNI for analyzing six data sets of
      solid cancers (liver, kidney, prostate, lung and germ cell) and found that top
      ranked FFLs account for ~20% of transcriptome changes between normal and cancer.
      We have identified common FFL regulators across multiple cancer types, such as
      known FFLs consisting of MYC and miR-15/miR-17 families, and novel FFLs
      consisting of ARNT, CREB1 and their miRNA partners. The results and analysis web
      server are available at http://www.canevolve.org/dChip-GemiNi.

PMID- 22645321
TI  - Protein frustratometer: a tool to localize energetic frustration in protein
      molecules.
AB  - The frustratometer is an energy landscape theory-inspired algorithm that aims at
      quantifying the location of frustration manifested in protein molecules.
      Frustration is a useful concept for gaining insight to the proteins biological
      behavior by analyzing how the energy is distributed in protein structures and how
      mutations or conformational changes shift the energetics. Sites of high local
      frustration often indicate biologically important regions involved in binding or
      allostery. In contrast, minimally frustrated linkages comprise a stable folding
      core of the molecule that is conserved in conformational changes. Here, we
      describe the implementation of these ideas in a webserver freely available at the
      National EMBNet node-Argentina, at URL: http://lfp.qb.fcen.uba.ar/embnet/.

PMID- 22645322
TI  - How early renal biopsy has to be performed in children with isolated asymptomatic
      proteinuria?

PMID- 22645323
TI  - Steroid avoidance with early intensified dosing of enteric-coated mycophenolate
      sodium: a randomized multicentre trial in kidney transplant recipients.
AB  - BACKGROUND: Short-term intensified dosing using enteric-coated mycophenolate
      sodium (EC-MPS) reduces rejection after kidney transplantation without
      compromising safety and may facilitate steroid avoidance. METHODS: In a 6-month,
      multicentre open-label trial, 222 de novo kidney transplant recipients at low
      immunological risk were randomized to steroid avoidance or maintenance steroids
      with interleukin (IL)-2 receptor antibody (IL-2RA) induction, EC-MPS (2160 mg/day
      to Week 6, 1440 mg/day thereafter) and cyclosporine. RESULTS: The primary end
      point; treatment failure at Month 6 [biopsy-proven acute rejection (BPAR), graft
      loss, death or loss to follow-up], occurred in 17.9% (20/112) of steroid
      avoidance patients and 14.5% (16/110) of controls (difference 3.4%, 95%
      confidence interval -6.3 to 13.1, P = 0.47 for superiority testing). BPAR
      occurred in 11.6 and 7.3% of patients in the steroid-avoidance and control arms,
      respectively (P = 0.27). Creatinine clearance was similar at Month 6 (steroid
      avoidance 56 +/- 18 mL/min/1.73 m(2), controls 60 +/- 22 mL/min/1.73 m(2), P =
      0.34). Cytomegalovirus infection, as reported by investigators, occurred in 12.5%
      of steroid-avoidance patients and 22.7% of controls (P = 0.045). CONCLUSIONS: A
      regimen of early intensified EC-MPS dosing with calcineurin inhibitor and IL-2RA
      induction permits oral steroid avoidance in adult kidney transplant patients at
      low-immunological risk without compromising efficacy at 6 months' follow-up.

PMID- 22645324
TI  - Calcium nephrolithiasis, metabolic syndrome and the cardiovascular risk.

PMID- 22645325
TI  - Nested case-control study of night shift work and breast cancer risk among women
      in the Danish military.
AB  - OBJECTIVES: Growing but limited evidence suggests that night shift work is
      associated with breast cancer. The authors conducted a nationwide case-control
      study nested within a cohort of 18,551 female military employees born in 1929
      1968 to investigate the risk for breast cancer after night shift work and to
      explore the role of leisure time sun exposure and diurnal preference. METHODS:
      The authors documented 218 cases of breast cancer (1990-2003) and selected 899
      age-matched controls from the cohort by incidence density sampling. Information
      on shift work, sun exposure habits, diurnal preference and other potential
      confounders was obtained from a structured questionnaire. ORs were estimated by
      multivariate conditional logistic regression. RESULTS: Overall, the authors
      observed an adjusted OR of 1.4 (95% CI 0.9 to 2.1) among women with ever compared
      with never night shifts. The RR for breast cancer tended to increase with
      increasing number of years of night shift work (p=0.03) and with cumulative
      number of shifts (p=0.02),with a neutral risk for fewer than three night shifts
      per week. The OR for the group with the highest tertile of cumulative exposure
      was 2.3 (95% CI 1.2 to 4.6). The most pronounced effect of night shift work on
      breast cancer risk was observed in women with morning chronotype preference and
      intense night shifts (OR=3.9, 95% CI 1.6 to 9.5). Night shift workers tended to
      sunbathe more frequently than day workers. CONCLUSIONS: The results indicate that
      frequent night shift work increases the risk for breast cancer and suggest a
      higher risk with longer duration of intense night shifts. Women with morning
      preference who worked on night shifts tended to have a higher risk than those
      with evening preference.

PMID- 22645326
TI  - piggyBac transposition into primordial germ cells is an efficient tool for
      transgenesis in chickens.
AB  - Transgenic birds embody one of the most potent and exciting research tools in
      biotechnology for agriculture, medicine, and model animals. To date, retrovirus-
      or lentivirus-mediated transgenesis has been established in chickens and quail.
      However, despite having a valid technique for viral transduction to achieve
      transgenic birds, many obstacles exist for practical applications because of
      relatively low and variable rates of germ-line transmission and transgenic
      offspring showing transgene silencing, as well as safety issues related to viral
      vector use. Thus, the generation of transgenic poultry by nonviral integration is
      a prerequisite for the introduction of biotechnology to practical applications.
      Herein, we show that a germ-line-competent chicken primordial germ-cell (PGC)
      line was established with high efficiency of transmission to offspring and that
      piggyBac transposition into PGCs improved the efficiency of transgenic chicken
      production and led to high-level transgene expression. GFP transgene-expressing
      donor PGC-transferred recipient chickens produced donor-derived progenies, and
      the germ-line transmission efficiency of donor PGCs was 95.2% on average.
      Subsequently, half of the donor-derived offspring (52.2%) were transgenic chicks
      because GFP-expressing donor PGCs, in which a transgene was inserted into one
      chromosome 20, were heterozygous. In all of the transgenic chickens, GFP
      expression was constant and strong, regardless of age. Our results demonstrate
      that piggyBac transposition into the chicken PGC line could be the surest way to
      generate transgenic chickens safely for practical applications.

PMID- 22645327
TI  - Sex-lethal enables germline stem cell differentiation by down-regulating Nanos
      protein levels during Drosophila oogenesis.
AB  - Drosophila ovarian germ cells require Sex-lethal (Sxl) to exit from the stem cell
      state and to enter the differentiation pathway. Sxl encodes a female-specific RNA
      binding protein and in somatic cells serves as the developmental switch gene for
      somatic sex determination and X-chromosome dosage compensation. None of the known
      Sxl target genes are required for germline differentiation, leaving open the
      question of how Sxl promotes the transition from stem cell to committed daughter
      cell. We address the mechanism by which Sxl regulates this transition through the
      identification of nanos as one of its target genes. Previous studies have shown
      that Nanos protein is necessary for GSC self-renewal and is rapidly down
      regulated in the daughter cells fated to differentiate in the adult ovary. We
      find that this dynamic expression pattern is limited to female germ cells and is
      under Sxl control. In the absence of Sxl, or in male germ cells, Nanos protein is
      continuously expressed. Furthermore, this female-specific expression pattern is
      dependent on the presence of canonical Sxl binding sites located in the nanos 3'
      untranslated region. These results, combined with the observation that nanos RNA
      associates with the Sxl protein in ovarian extracts and loss and gain of function
      studies, suggest that Sxl enables the switch from germline stem cell to committed
      daughter cell by posttranscriptional down-regulation of nanos expression. These
      findings connect sexual identity to the stem cell self-renewal/differentiation
      decision and highlight the importance of posttranscriptional gene regulatory
      networks in controlling stem cell behavior.

PMID- 22645328
TI  - Cyanobacteria blooms produce teratogenic retinoic acids.
AB  - Deformed amphibians have been observed in eutrophic habitats, and some clues
      point to the retinoic acids (RAs) or RA mimics. However, RAs are generally
      thought of as vertebrate-specific hormones, and there was no evidence that RAs
      exist in cyanobacteria or algae blooms. By analyzing RAs and their analogs 4-oxo
      RAs in natural cyanobacteria blooms and cultures of cyanobacteria and algae, we
      showed that cyanobacteria blooms could produce RAs, which were powerful animal
      teratogens. Intracellular RAs and 4-oxo-RAs with concentrations between 0.4 and
      4.2 * 10(2) ng/L were detected in all bloom materials, and extracellular
      concentrations measured in water from Taihu Lake, China, were as great as 2.0 *
      10 ng/L, which might pose a risk to wildlife through chronic exposure. Further
      examination of 39 cyanobacteria and algae species revealed that 32 species could
      produce RAs and 4-oxo-RAs (1.6-1.4 * 10(3) ng/g dry weight), and the dominant
      cyanobacteria species in Taihu Lake, Microcystis flos-aquae and Microcystis
      aeruginosa, produced high amounts of RAs and 4-oxo-RAs with concentrations of 1.4
      * 10(3) and 3.7 * 10(2) ng/g dry weight, respectively. Most genera of
      cyanobacteria that could produce RAs and 4-oxo-RAs, such as Microcystis,
      Anabaena, and Aphanizomenon, often occur dominantly in blooms. Production of RAs
      and 4-oxo-RAs by cyanobacteria was associated with species, origin location, and
      growth stage. These results represent a conclusive demonstration of endogenous
      production of RAs in freshwater cyanobacteria blooms. The observation of
      teratogenic RAs in cyanobacteria is evolutionarily and ecologically significant
      because RAs are vertebrate-specific hormones, and cyanobacteria form extensive
      and highly visible blooms in many aquatic ecosystems.

PMID- 22645329
TI  - Erythropoietin-induced changes in brain gene expression reveal induction of
      synaptic plasticity genes in experimental stroke.
AB  - Erythropoietin (EPO) is a neuroprotective cytokine in models of ischemic and
      nervous system injury, where it reduces neuronal apoptosis and inflammatory
      cytokines and increases neurogenesis and angiogenesis. EPO also improves
      cognition in healthy volunteers and schizophrenic patients. We studied the effect
      of EPO administration on the gene-expression profile in the ischemic cortex of
      rats after cerebral ischemia at early time points (2 and 6 h). EPO treatment up
      regulated genes already increased by ischemia. Hierarchical clustering and
      analysis of overrepresented functional categories identified genes implicated in
      synaptic plasticity-Arc, BDNF, Egr1, and Egr2, of which Egr2 was the most
      significantly regulated. Up-regulation of Arc, BDNF, Dusp5, Egr1, Egr2, Egr4, and
      Nr4a3 was confirmed by quantitative PCR. We investigated the up-regulation of
      Egr2/Krox20 further because of its role in neuronal plasticity. Its elevation by
      EPO was confirmed in an independent in vivo experiment of cerebral ischemia in
      rats. Using the rat neuroblastoma B104, we found that wild-type cells that do not
      express EPO receptor (EPOR) do not respond to EPO by inducing Egr2. However, EPOR
      expressing B104 cells induce Egr2 early upon incubation with EPO, indicating that
      Egr2 induction is a direct effect of EPO and that EPOR mediates this effect.
      Because these changes occur in vivo before decreased inflammatory cytokines or
      neuronal apoptosis is evident, these findings provide a molecular mechanism for
      the neuroreparative effects of cytokines and suggest a mechanism of
      neuroprotection by which promotion of a plastic phenotype results in decreased
      inflammation and neuronal death.

PMID- 22645330
TI  - Human origins and the transition from promiscuity to pair-bonding.
AB  - A crucial step in recent theories of human origins is the emergence of strong
      pair-bonding between males and females accompanied by a dramatic reduction in the
      male-to-male conflict over mating and an increased investment in offspring. How
      such a transition from promiscuity to pair-bonding could be achieved is puzzling.
      Many species would, indeed, be much better off evolutionarily if the effort spent
      on male competition over mating was redirected to increasing female fertility or
      survivorship of offspring. Males, however, are locked in a "social dilemma,"
      where shifting one's effort from "appropriation" to "production" would give an
      advantage to free-riding competitors and therefore, should not happen. Here, I
      first consider simple models for four prominent scenarios of the human transition
      to pair-bonding: communal care, mate guarding, food for mating, and mate
      provisioning. I show that the transition is not feasible under biologically
      relevant conditions in any of these models. Then, I show that the transition can
      happen if one accounts for male heterogeneity, assortative pair formation, and
      evolution of female choice and faithfulness. This process is started when low
      ranked males begin using an alternative strategy of female provisioning. At the
      end, except for the top-ranked individuals, males invest exclusively in
      provisioning females who have evolved very high fidelity to their mates. My
      results point to the crucial importance of female choice and emphasize the need
      for incorporating between-individual variation in theoretical and empirical
      studies of social dilemmas and behaviors.

PMID- 22645331
TI  - BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA
      repression during human cytomegalovirus infection.
AB  - Cell proteins can restrict the replication of viruses. Here, we identify the
      cellular BclAF1 protein as a human cytomegalovirus restriction factor and
      describe two independent mechanisms the virus uses to decrease its steady-state
      levels. Immediately following infection, the viral pp71 and UL35 proteins, which
      are delivered to cells within virions, direct the proteasomal degradation of
      BclAF1. Although BclAF1 reaccumulates through the middle stages of infection, it
      is subsequently down-regulated at late times by miR-UL112-1, a virus-encoded
      microRNA. In the absence of BclAF1 neutralization, viral gene expression and
      replication are inhibited. These data identify two temporally and mechanistically
      distinct functions used by human cytomegalovirus to down-regulate a cellular
      antiviral protein.

PMID- 22645332
TI  - Community differentiation and kinship among Europe's first farmers.
AB  - Community differentiation is a fundamental topic of the social sciences, and its
      prehistoric origins in Europe are typically assumed to lie among the complex,
      densely populated societies that developed millennia after their Neolithic
      predecessors. Here we present the earliest, statistically significant evidence
      for such differentiation among the first farmers of Neolithic Europe. By using
      strontium isotopic data from more than 300 early Neolithic human skeletons, we
      find significantly less variance in geographic signatures among males than we
      find among females, and less variance among burials with ground stone adzes than
      burials without such adzes. From this, in context with other available evidence,
      we infer differential land use in early Neolithic central Europe within a
      patrilocal kinship system.

PMID- 22645333
TI  - Identification of an abscisic acid transporter by functional screening using the
      receptor complex as a sensor.
AB  - Movement of the plant hormone abscisic acid (ABA) within plants has been
      documented; however, the molecular mechanisms that regulate ABA transport are not
      fully understood. By using a modified yeast two-hybrid system, we screened
      Arabidopsis cDNAs capable of inducing interactions between the ABA receptor
      PYR/PYL/RCAR and PP2C protein phosphatase under low ABA concentrations. By using
      this approach, we identified four members of the NRT1/PTR family as candidates
      for ABA importers. Transport assays in yeast and insect cells demonstrated that
      at least one of the candidates ABA-IMPORTING TRANSPORTER (AIT) 1, which had been
      characterized as the low-affinity nitrate transporter NRT1.2, mediates cellular
      ABA uptake. Compared with WT, the ait1/nrt1.2 mutants were less sensitive to
      exogenously applied ABA during seed germination and/or postgermination growth,
      whereas overexpression of AIT1/NRT1.2 resulted in ABA hypersensitivity in the
      same conditions. Interestingly, the inflorescence stems of ait1/nrt1.2 had a
      lower surface temperature than those of the WT because of excess water loss from
      open stomata. We detected promoter activities of AIT1/NRT1.2 around vascular
      tissues in inflorescence stems, leaves, and roots. These data suggest that the
      function of AIT1/NRT1.2 as an ABA importer at the site of ABA biosynthesis is
      important for the regulation of stomatal aperture in inflorescence stems.

PMID- 22645334
TI  - Extra twist in magnetic bubbles.

PMID- 22645335
TI  - Nuclear export, enlightened.

PMID- 22645336
TI  - Ecological and evolutionary dynamics of coexisting lineages during a long-term
      experiment with Escherichia coli.
AB  - Closely related organisms usually occupy similar ecological niches, leading to
      intense competition and even extinction. Such competition also can promote rapid
      phenotypic evolution and ecological divergence. This process may end with the
      stable occupation of distinct niches or, alternatively, may entail repeated bouts
      of evolution. Here we examine two Escherichia coli lineages, called L and S, that
      coexisted for more than 30,000 generations after diverging from a common
      ancestor. Both lineages underwent sustained phenotypic evolution based on global
      transcription and resource utilization profiles, with L seeming to encroach over
      time on the catabolic profile of S. Reciprocal invasion experiments with L and S
      clones from the same or different generations revealed evolutionary changes in
      their interaction, including an asymmetry that confirmed the encroachment by L on
      the niche of the S lineage. In general, L and S clones from the same generation
      showed negative frequency-dependent effects, consistent with stable coexistence.
      However, L clones could invade S clones from both earlier and later generations,
      whereas S clones could invade only L clones from earlier generations. In this
      system, the long-term coexistence of competing lineages evidently depended on
      successive rounds of evolution, rather than on initial divergence followed by a
      static equilibrium.

PMID- 22645337
TI  - Profile of Ira Mellman. Interview by Prashant Nair.

PMID- 22645338
TI  - Joint control of Drosophila male courtship behavior by motion cues and activation
      of male-specific P1 neurons.
AB  - Sexual behaviors in animals are governed by inputs from multiple external sensory
      modalities. However, how these inputs are integrated to jointly control animal
      behavior is still poorly understood. Whereas visual information alone is not
      sufficient to induce courtship behavior in Drosophila melanogaster males, when a
      subset of male-specific fruitless (fru)- and doublesex (dsx)-expressing neurons
      that respond to chemosensory cues (P1 neurons) were artificially activated via a
      temperature-sensitive cation channel (dTRPA1), males followed and extended their
      wing toward moving objects (even a moving piece of rubber band) intensively. When
      stationary, these objects were not courted. Our results indicate that motion
      input and activation of P1 neurons are individually necessary, and under our
      assay conditions, jointly sufficient to elicit early courtship behaviors, and
      provide insights into how courtship decisions are made via sensory integration.

PMID- 22645339
TI  - Transcriptional repression via antilooping in the Drosophila embryo.
AB  - Transcriptional repressors are thought to inhibit gene expression by interfering
      with the binding or function of RNA Polymerase II, perhaps by promoting local
      chromatin condensation. Here, we present evidence for a distinctive mechanism of
      repression, whereby sequence-specific repressors prevent the looping of distal
      enhancers to the promoter. Particular efforts focus on the Snail repressor, which
      plays a conserved role in promoting epithelial-mesenchyme transitions in both
      invertebrates and vertebrates, including mesoderm invagination in Drosophila,
      neural crest migration in vertebrates, and tumorigenesis in mammals. Chromosome
      conformation capture experiments were used to examine enhancer looping at Snail
      target genes in wild-type and mutant embryos. These studies suggest that the
      Snail repressor blocks the formation of fruitful enhancer-promoter interactions
      when bound to a distal enhancer. This higher-order mechanism of transcriptional
      repression has broad implications for the control of gene activity in metazoan
      development.

PMID- 22645340
TI  - Position coding in the visual word form area.

PMID- 22645341
TI  - Ice-binding site of snow mold fungus antifreeze protein deviates from structural
      regularity and high conservation.
AB  - Antifreeze proteins (AFPs) are found in organisms ranging from fish to bacteria,
      where they serve different functions to facilitate survival of their host. AFPs
      that protect freeze-intolerant fish and insects from internal ice growth bind to
      ice using a regular array of well-conserved residues/motifs. Less is known about
      the role of AFPs in freeze-tolerant species, which might be to beneficially alter
      the structure of ice in or around the host. Here we report the 0.95-A high
      resolution crystal structure of a 223-residue secreted AFP from the snow mold
      fungus Typhula ishikariensis. Its main structural element is an irregular beta
      helix with six loops of 18 or more residues that lies alongside an alpha-helix.
      beta-Helices have independently evolved as AFPs on several occasions and seem
      ideally structured to bind to several planes of ice, including the basal plane. A
      novelty of the beta-helical fold is the nonsequential arrangement of loops that
      places the N- and C termini inside the solenoid of beta-helical coils. The ice
      binding site (IBS), which could not be predicted from sequence or structure, was
      located by site-directed mutagenesis to the flattest surface of the protein. It
      is remarkable for its lack of regularity and its poor conservation in homologs
      from psychrophilic diatoms and bacteria and other fungi.

PMID- 22645342
TI  - Noninvasive in vivo optical detection of biofilm in the human middle ear.
AB  - Otitis media (OM), a middle-ear infection, is the most common childhood illness
      treated by pediatricians. If inadequately treated, OM can result in long-term
      chronic problems persisting into adulthood. Children with chronic OM or recurrent
      OM often have conductive hearing loss and communication difficulties and require
      surgical treatment. Tympanostomy tube insertion, the placement of a small
      drainage tube in the tympanic membrane (TM), is the most common surgical
      procedure performed in children under general anesthesia. Recent clinical studies
      have shown evidence of a direct correspondence between chronic OM and the
      presence of a bacterial biofilm within the middle ear. Biofilms are typically
      very thin and cannot be recognized using a regular otoscope. Here we report the
      use of optical coherent ranging techniques to noninvasively assess the middle ear
      to detect and quantify biofilm microstructure. This study involves adults with
      chronic OM, which is generally accepted as a biofilm-related disease. Based on
      more than 18,537 optical ranging scans and 742 images from 13 clinically infected
      patients and 7 normal controls using clinical findings as the gold standard, all
      middle ears with chronic OM showed evidence of biofilms, and all normal ears did
      not. Information on the presence of a biofilm, along with its structure and
      response to antibiotic treatment, will not only provide a better fundamental
      understanding of biofilm formation, growth, and eradication in the middle ear,
      but also may provide much-needed quantifiable data to enable early detection and
      quantitative longitudinal treatment monitoring of middle-ear biofilms responsible
      for chronic OM.

PMID- 22645343
TI  - Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum
      HIV-1 inhibitor.
AB  - The natural history of HIV-1 infection is highly variable in different
      individuals, spanning from a rapidly progressive course to a long-term
      asymptomatic infection. A major determinant of the pace of disease progression is
      the in vivo level of HIV-1 replication, which is regulated by a complex network
      of cytokines and chemokines expressed by immune and inflammatory cells. The
      chemokine system is critically involved in the control of HIV-1 replication by
      virtue of the role played by specific chemokine receptors, most notably CCR5 and
      CXCR4, as cell-surface coreceptors for HIV-1 entry; hence, the chemokines that
      naturally bind such coreceptors act as endogenous inhibitors of HIV-1. Here, we
      show that the CXC chemokine CXCL4 (PF-4), the most abundant protein contained
      within the alpha-granules of platelets, is a broad-spectrum inhibitor of HIV-1
      infection. Unlike other known HIV-suppressive chemokines, CXCL4 inhibits
      infection by the majority of primary HIV-1 isolates regardless of their
      coreceptor-usage phenotype or genetic subtype. Consistent with the lack of viral
      phenotype specificity, blockade of HIV-1 infection occurs at the level of virus
      attachment and entry via a unique mechanism that involves direct interaction of
      CXCL4 with the major viral envelope glycoprotein, gp120. The binding site for
      CXCL4 was mapped to a region of the gp120 outer domain proximal to the CD4
      binding site. The identification of a platelet-derived chemokine as an endogenous
      antiviral factor may have relevance for the pathogenesis and treatment of HIV-1
      infection.

PMID- 22645344
TI  - Small RNA binding to the lateral surface of Hfq hexamers and structural
      rearrangements upon mRNA target recognition.
AB  - The bacterial Sm-like protein Hfq is a central player in the control of bacterial
      gene expression. Hfq forms complexes with small regulatory RNAs (sRNAs) that use
      complementary "seed" sequences to target specific mRNAs. Hfq forms hexameric
      rings, which preferably bind uridine-rich RNA 3' ends on their proximal surface
      and adenine-rich sequences on their distal surface. However, many reported
      properties of Hfq/sRNA complexes could not be explained by these RNA binding
      modes. Here, we use the RybB sRNA to identify the lateral surface of Hfq as a
      third, independent RNA binding surface. A systematic mutational analysis and
      competition experiments demonstrate that the lateral sites have a preference for
      and are sufficient to bind the sRNA "body," including the seed sequence.
      Furthermore, we detect significant structural rearrangements of the Hfq/sRNA
      complex upon mRNA target recognition that lead to a release of the seed sequence,
      or of the entire sRNA molecule in case of an unfavorable 3' end. Consequently, we
      propose a molecular model for the Hfq/sRNA complex, where the sRNA 3' end is
      anchored in the proximal site of Hfq, whereas the sRNA body, including the seed
      sequence, is bound by up to six of the lateral sites. In contrast to previously
      proposed arrangements, the presented model explains how Hfq can protect large
      parts of the sRNA body while still allowing a rapid recycling of sRNAs.
      Furthermore, our model suggests molecular mechanisms for the function of Hfq as
      an RNA chaperone and for the molecular events that are initiated upon mRNA target
      recognition.

PMID- 22645346
TI  - Pacific bluefin tuna transport Fukushima-derived radionuclides from Japan to
      California.
AB  - The Fukushima Dai-ichi release of radionuclides into ocean waters caused
      significant local and global concern regarding the spread of radioactive
      material. We report unequivocal evidence that Pacific bluefin tuna, Thunnus
      orientalis, transported Fukushima-derived radionuclides across the entire North
      Pacific Ocean. We measured gamma-emitting radionuclides in California-caught
      tunas and found (134)Cs (4.0 +/- 1.4 Bq kg(-1)) and elevated (137)Cs (6.3 +/- 1.5
      Bq kg(-1)) in 15 Pacific bluefin tuna sampled in August 2011. We found no (134)Cs
      and background concentrations (~1 Bq kg(-1)) of (137)Cs in pre-Fukushima bluefin
      and post-Fukushima yellowfin tunas, ruling out elevated radiocesium uptake before
      2011 or in California waters post-Fukushima. These findings indicate that Pacific
      bluefin tuna can rapidly transport radionuclides from a point source in Japan to
      distant ecoregions and demonstrate the importance of migratory animals as
      transport vectors of radionuclides. Other large, highly migratory marine animals
      make extensive use of waters around Japan, and these animals may also be
      transport vectors of Fukushima-derived radionuclides to distant regions of the
      North and South Pacific Oceans. These results reveal tools to trace migration
      origin (using the presence of (134)Cs) and potentially migration timing (using
      (134)Cs:(137)Cs ratios) in highly migratory marine species in the Pacific Ocean.

PMID- 22645345
TI  - Stress and aging induce distinct polyQ protein aggregation states.
AB  - Many age-related diseases are known to elicit protein misfolding and aggregation.
      Whereas environmental stressors, such as temperature, oxidative stress, and
      osmotic stress, can also damage proteins, it is not known whether aging and the
      environment impact protein folding in the same or different ways. Using polyQ
      reporters of protein folding in both Caenorhabditis elegans and mammalian cell
      culture, we show that osmotic stress, but not other proteotoxic stressors,
      induces rapid (minutes) cytoplasmic polyQ aggregation. Osmotic stress-induced
      polyQ aggregates could be distinguished from aging-induced polyQ aggregates based
      on morphological, biophysical, cell biological, and biochemical criteria,
      suggesting that they are a unique misfolded-protein species. The insulin-like
      growth factor signaling mutant daf-2, which inhibits age-induced polyQ
      aggregation and protects C. elegans from stress, did not prevent the formation of
      stress-induced polyQ aggregates. However, osmotic stress resistance mutants,
      which genetically activate the osmotic stress response, strongly inhibited the
      formation of osmotic polyQ aggregates. Our findings show that in vivo, the same
      protein can adopt distinct aggregation states depending on the initiating
      stressor and that stress and aging impact the proteome in related but distinct
      ways.

PMID- 22645347
TI  - Structure of the receptor-binding carboxy-terminal domain of bacteriophage T7
      tail fibers.
AB  - The six bacteriophage T7 tail fibers, homo-trimers of gene product 17, are
      thought to be responsible for the first specific, albeit reversible, attachment
      to Escherichia coli lipopolysaccharide. The protein trimer forms kinked fibers
      comprised of an amino-terminal tail-attachment domain, a slender shaft, and a
      carboxyl-terminal domain composed of several nodules. Previously, we expressed,
      purified, and crystallized a carboxyl-terminal fragment comprising residues 371
      553. Here, we report the structure of this protein trimer, solved using anomalous
      diffraction and refined at 2 A resolution. Amino acids 371-447 form a tapered
      pyramid with a triangular cross-section composed of interlocked beta-sheets from
      each of the three chains. The triangular pyramid domain has three alpha-helices
      at its narrow end, which are connected to a carboxyl-terminal three-blade beta
      propeller tip domain by flexible loops. The monomers of this tip domain each
      contain an eight-stranded beta-sandwich. The exact topology of the beta-sandwich
      fold is novel, but similar to that of knob domains of other viral fibers and the
      phage Sf6 needle. Several host-range change mutants have been mapped to loops
      located on the top of this tip domain, suggesting that this surface of the tip
      domain interacts with receptors on the cell surface.

PMID- 22645348
TI  - Robust cardiomyocyte differentiation from human pluripotent stem cells via
      temporal modulation of canonical Wnt signaling.
AB  - Human pluripotent stem cells (hPSCs) offer the potential to generate large
      numbers of functional cardiomyocytes from clonal and patient-specific cell
      sources. Here we show that temporal modulation of Wnt signaling is both essential
      and sufficient for efficient cardiac induction in hPSCs under defined, growth
      factor-free conditions. shRNA knockdown of beta-catenin during the initial stage
      of hPSC differentiation fully blocked cardiomyocyte specification, whereas
      glycogen synthase kinase 3 inhibition at this point enhanced cardiomyocyte
      generation. Furthermore, sequential treatment of hPSCs with glycogen synthase
      kinase 3 inhibitors followed by inducible expression of beta-catenin shRNA or
      chemical inhibitors of Wnt signaling produced a high yield of virtually (up to
      98%) pure functional human cardiomyocytes from multiple hPSC lines. The robust
      ability to generate functional cardiomyocytes under defined, growth factor-free
      conditions solely by genetic or chemically mediated manipulation of a single
      developmental pathway should facilitate scalable production of cardiac cells
      suitable for research and regenerative applications.

PMID- 22645349
TI  - Distinct CD4+ helper T cells involved in primary and secondary responses to
      infection.
AB  - Helper T cells are critical for protective immunity, CD8(+) T-cell memory, and
      CD4(+) recall responses, but whether the same or distinct CD4(+) T cells are
      involved in these responses has not been established. Here we describe two CD4(+)
      T cells, LLO118 and LLO56, specific for an immunodominant Listeria monocytogenes
      epitope, with dramatically different responses to primary and secondary
      infection. Comparing in vivo responses, LLO118 T cells proliferate more strongly
      to primary infection, whereas surprisingly, LLO56 has a superior CD4(+) recall
      response to secondary infection. LLO118 T cells provide more robust help for
      CD8(+) T-cell responses to secondary infection than LLO56. We found no detectable
      differences in antigen sensitivity, but naive LLO118 T cells have much lower
      levels of CD5 and their T-cell receptor levels are dramatically down-regulated
      after their strong primary response. Thus, distinct CD4(+) helper T cells are
      specialized to help either in primary or secondary responses to infection.

PMID- 22645350
TI  - Top performers are not the most impressive when extreme performance indicates
      unreliability.
AB  - The relationship between performance and ability is a central concern in the
      social sciences: Are the most successful much more able than others, and are
      failures unskilled? Prior research has shown that noise and self-reinforcing
      dynamics make performance unpredictable and lead to a weak association between
      ability and performance. Here we show that the same mechanisms that generate
      unpredictability imply that extreme performances can be relatively uninformative
      about ability. As a result, the highest performers may not have the highest
      expected ability and should not be imitated or praised. We show that whether
      higher performance indicates higher ability depends on whether extreme
      performance could be achieved by skill or requires luck.

PMID- 22645351
TI  - 3' Phosphatase activity toward phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2]
      by voltage-sensing phosphatase (VSP).
AB  - Voltage-sensing phosphatases (VSPs) consist of a voltage-sensor domain and a
      cytoplasmic region with remarkable sequence similarity to phosphatase and tensin
      homolog deleted on chromosome 10 (PTEN), a tumor suppressor phosphatase. VSPs
      dephosphorylate the 5' position of the inositol ring of both phosphatidylinositol
      3,4,5-trisphosphate [PI(3,4,5)P(3)] and phosphatidylinositol 4,5-bisphosphate
      [PI(4,5)P(2)] upon voltage depolarization. However, it is unclear whether VSPs
      also have 3' phosphatase activity. To gain insights into this question, we
      performed in vitro assays of phosphatase activities of Ciona intestinalis VSP (Ci
      VSP) and transmembrane phosphatase with tensin homology (TPTE) and PTEN
      homologous inositol lipid phosphatase (TPIP; one human ortholog of VSP) with
      radiolabeled PI(3,4,5)P(3). TLC assay showed that the 3' phosphate of
      PI(3,4,5)P(3) was not dephosphorylated, whereas that of phosphatidylinositol 3,4
      bisphosphate [PI(3,4)P(2)] was removed by VSPs. Monitoring of PI(3,4)P(2) levels
      with the pleckstrin homology (PH) domain from tandem PH domain-containing protein
      (TAPP1) fused with GFP (PH(TAPP1)-GFP) by confocal microscopy in amphibian
      oocytes showed an increase of fluorescence intensity during depolarization to 0
      mV, consistent with 5' phosphatase activity of VSP toward PI(3,4,5)P(3). However,
      depolarization to 60 mV showed a transient increase of GFP fluorescence followed
      by a decrease, indicating that, after PI(3,4,5)P(3) is dephosphorylated at the 5'
      position, PI(3,4)P(2) is then dephosphorylated at the 3' position. These results
      suggest that substrate specificity of the VSP changes with membrane potential.

PMID- 22645352
TI  - Groundwater depletion and sustainability of irrigation in the US High Plains and
      Central Valley.
AB  - Aquifer overexploitation could significantly impact crop production in the United
      States because 60% of irrigation relies on groundwater. Groundwater depletion in
      the irrigated High Plains and California Central Valley accounts for ~50% of
      groundwater depletion in the United States since 1900. A newly developed High
      Plains recharge map shows that high recharge in the northern High Plains results
      in sustainable pumpage, whereas lower recharge in the central and southern High
      Plains has resulted in focused depletion of 330 km(3) of fossil groundwater,
      mostly recharged during the past 13,000 y. Depletion is highly localized with
      about a third of depletion occurring in 4% of the High Plains land area.
      Extrapolation of the current depletion rate suggests that 35% of the southern
      High Plains will be unable to support irrigation within the next 30 y. Reducing
      irrigation withdrawals could extend the lifespan of the aquifer but would not
      result in sustainable management of this fossil groundwater. The Central Valley
      is a more dynamic, engineered system, with north/south diversions of surface
      water since the 1950s contributing to ~7* higher recharge. However, these
      diversions are regulated because of impacts on endangered species. A newly
      developed Central Valley Hydrologic Model shows that groundwater depletion since
      the 1960s, totaling 80 km(3), occurs mostly in the south (Tulare Basin) and
      primarily during droughts. Increasing water storage through artificial recharge
      of excess surface water in aquifers by up to 3 km(3) shows promise for coping
      with droughts and improving sustainability of groundwater resources in the
      Central Valley.

PMID- 22645353
TI  - Coordinated phenotype switching with large-scale chromosome flip-flop inversion
      observed in bacteria.
AB  - Genome inversions are ubiquitous in organisms ranging from prokaryotes to
      eukaryotes. Typical examples can be identified by comparing the genomes of two or
      more closely related organisms, where genome inversion footprints are clearly
      visible. Although the evolutionary implications of this phenomenon are huge,
      little is known about the function and biological meaning of this process. Here,
      we report our findings on a bacterium that generates a reversible, large-scale
      inversion of its chromosome (about half of its total genome) at high frequencies
      of up to once every four generations. This inversion switches on or off bacterial
      phenotypes, including colony morphology, antibiotic susceptibility, hemolytic
      activity, and expression of dozens of genes. Quantitative measurements and
      mathematical analyses indicate that this reversible switching is stochastic but
      self-organized so as to maintain two forms of stable cell populations (i.e.,
      small colony variant, normal colony variant) as a bet-hedging strategy. Thus,
      this heritable and reversible genome fluctuation seems to govern the bacterial
      life cycle; it has a profound impact on the course and outcomes of bacterial
      infections.

PMID- 22645354
TI  - Fibrogenic cell reversion underlies fibrosis regression in liver.

PMID- 22645355
TI  - Development of insulin resistance in mice lacking PGC-1alpha in adipose tissues.
AB  - Reduced peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC
      1alpha) expression and mitochondrial dysfunction in adipose tissue have been
      associated with obesity and insulin resistance. Whether this association is
      causally involved in the development of insulin resistance or is only a
      consequence of this condition has not been clearly determined. Here we studied
      the effects of adipose-specific deficiency of PGC-1alpha on systemic glucose
      homeostasis. Loss of PGC-1alpha in white fat resulted in reduced expression of
      the thermogenic and mitochondrial genes in mice housed at ambient temperature,
      whereas gene expression patterns in brown fat were not altered. When challenged
      with a high-fat diet, insulin resistance was observed in the mutant mice,
      characterized by reduced suppression of hepatic glucose output. Resistance to
      insulin was also associated with an increase in circulating lipids, along with a
      decrease in the expression of genes regulating lipid metabolism and fatty acid
      uptake in adipose tissues. Taken together, these data demonstrate a critical role
      for adipose PGC-1alpha in the regulation of glucose homeostasis and a potentially
      causal involvement in the development of insulin resistance.

PMID- 22645356
TI  - Heterogeneity in tuberculosis transmission and the role of geographic hotspots in
      propagating epidemics.
AB  - The importance of high-incidence "hotspots" to population-level tuberculosis (TB)
      incidence remains poorly understood. TB incidence varies widely across countries,
      but within smaller geographic areas (e.g., cities), TB transmission may be more
      homogeneous than other infectious diseases. We constructed a steady-state
      compartmental model of TB in Rio de Janeiro, replicating nine epidemiological
      variables (e.g., TB incidence) within 1% of their observed values. We estimated
      the proportion of TB transmission originating from a high-incidence hotspot (6.0%
      of the city's population, 16.5% of TB incidence) and the relative impact of TB
      control measures targeting the hotspot vs. the general community. If each case of
      active TB in the hotspot caused 0.5 secondary transmissions in the general
      community for each within-hotspot transmission, the 6.0% of people living in the
      hotspot accounted for 35.3% of city-wide TB transmission. Reducing the TB
      transmission rate (i.e., number of secondary infections per infectious case) in
      the hotspot to that in the general community reduced city-wide TB incidence by
      9.8% in year 5, and 29.7% in year 50-an effect similar to halving time to
      diagnosis for the remaining 94% of the community. The importance of the hotspot
      to city-wide TB control depended strongly on the extent of TB transmission from
      the hotspot to the general community. High-incidence hotspots may play an
      important role in propagating TB epidemics. Achieving TB control targets in a
      hotspot containing 6% of a city's population can have similar impact on city-wide
      TB incidence as achieving the same targets throughout the remaining community.

PMID- 22645357
TI  - Inhibition of S-phase kinase-associated protein 2 (Skp2) reprograms and converts
      diabetogenic T cells to Foxp3+ regulatory T cells.
AB  - Autoreactive pathogenic T cells (Tpaths) and regulatory T cells (Tregs) express a
      distinct gene profiles; however, the genes and associated genetic/signaling
      pathways responsible for the functional determination of Tpaths vs. Tregs remain
      unknown. Here we show that Skp2, an E3 ubiquitin ligase that affects cell cycle
      control and death, plays a critical role in the function of diabetogenic Tpaths
      and Tregs. Down-regulation of Skp2 in diabetogenic Tpaths converts them into
      Foxp3-expressing Tregs. The suppressive function of the Tpath-converted Tregs is
      dependent on increased production of TGF-beta/IL-10, and these Tregs are able to
      inhibit spontaneous diabetes in NOD mice. Like naturally arising Foxp3(+) nTregs,
      the converted Tregs are anergic cells with decreased proliferation and activation
      induced cell death. Skp2 down-regulation leads to Tpath-Treg conversion due at
      least in part to up-regulation of several genes involved in cell cycle control
      and genes in the Foxo family. Down-regulation of the cyclin-dependent kinase
      inhibitor p27 alone significantly attenuates the effect of Skp2 on Tpaths and
      reduces the suppressive function of converted Tregs; its effect is further
      improved with concomitant down-regulation of p21, Foxo1, and Foxo3. In
      comparison, Skp2 overexpression does not change Tpath function, but significantly
      decreases Foxp3 expression and abrogates the suppressive function of nTregs.
      These findings support the critical role of Skp2 in functional specification of
      Tpaths and Tregs, and demonstrate an important molecular mechanism mediating Skp2
      function in balancing immune tolerance during autoimmune disease development.

PMID- 22645358
TI  - Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection
      without accelerating the decay of latent infection.
AB  - HIV type 1 (HIV-1) persists within resting CD4(+) T cells despite antiretroviral
      therapy (ART). To better understand the kinetics by which resting cell infection
      (RCI) is established, we developed a mathematical model that accurately predicts
      (r = 0.65, P = 2.5 * 10(-4)) the initial frequency of RCI measured about 1 year
      postinfection, based on the time of ART initiation and the dynamic changes in
      viremia and CD4(+) T cells. In the largest cohort of patients treated during
      acute seronegative HIV infection (AHI) in whom RCI has been stringently
      quantified, we found that early ART reduced the generation of latently infected
      cells. Although RCI declined after the first year of ART in most acutely infected
      patients, there was a striking absence of decline when initial RCI frequency was
      less than 0.5 per million. Notably, low-level viremia was observed more
      frequently as RCI increased. Together these observations suggest that (i) the
      degree of RCI is directly related to the availability of CD4(+) T cells
      susceptible to HIV, whether viremia is controlled by the immune response and/or
      ART; and (ii) that two pools of infected resting CD4(+) T cells exist, namely,
      less stable cells, observable in patients in whom viremia is not well controlled
      in early infection, and extremely stable cells that are established despite early
      ART. These findings reinforce and extend the concept that new approaches will be
      needed to eradicate HIV infection, and, in particular, highlight the need to
      target the extremely small but universal, long-lived latent reservoir.

PMID- 22645359
TI  - Drug hypersensitivity caused by alteration of the MHC-presented self-peptide
      repertoire.
AB  - Idiosyncratic adverse drug reactions are unpredictable, dose-independent and
      potentially life threatening; this makes them a major factor contributing to the
      cost and uncertainty of drug development. Clinical data suggest that many such
      reactions involve immune mechanisms, and genetic association studies have
      identified strong linkages between drug hypersensitivity reactions to several
      drugs and specific HLA alleles. One of the strongest such genetic associations
      found has been for the antiviral drug abacavir, which causes severe adverse
      reactions exclusively in patients expressing the HLA molecular variant B*57:01.
      Abacavir adverse reactions were recently shown to be driven by drug-specific
      activation of cytokine-producing, cytotoxic CD8(+) T cells that required HLA
      B*57:01 molecules for their function; however, the mechanism by which abacavir
      induces this pathologic T-cell response remains unclear. Here we show that
      abacavir can bind within the F pocket of the peptide-binding groove of HLA
      B*57:01, thereby altering its specificity. This provides an explanation for HLA
      linked idiosyncratic adverse drug reactions, namely that drugs can alter the
      repertoire of self-peptides presented to T cells, thus causing the equivalent of
      an alloreactive T-cell response. Indeed, we identified specific self-peptides
      that are presented only in the presence of abacavir and that were recognized by T
      cells of hypersensitive patients. The assays that we have established can be
      applied to test additional compounds with suspected HLA-linked hypersensitivities
      in vitro. Where successful, these assays could speed up the discovery and
      mechanistic understanding of HLA-linked hypersensitivities, and guide the
      development of safer drugs.

PMID- 22645360
TI  - Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits
      the amyloid cascade.
AB  - The transthyretin amyloidoses (ATTR) are invariably fatal diseases characterized
      by progressive neuropathy and/or cardiomyopathy. ATTR are caused by aggregation
      of transthyretin (TTR), a natively tetrameric protein involved in the transport
      of thyroxine and the vitamin A-retinol-binding protein complex. Mutations within
      TTR that cause autosomal dominant forms of disease facilitate tetramer
      dissociation, monomer misfolding, and aggregation, although wild-type TTR can
      also form amyloid fibrils in elderly patients. Because tetramer dissociation is
      the rate-limiting step in TTR amyloidogenesis, targeted therapies have focused on
      small molecules that kinetically stabilize the tetramer, inhibiting TTR amyloid
      fibril formation. One such compound, tafamidis meglumine (Fx-1006A), has recently
      completed Phase II/III trials for the treatment of Transthyretin Type Familial
      Amyloid Polyneuropathy (TTR-FAP) and demonstrated a slowing of disease
      progression in patients heterozygous for the V30M TTR mutation. Herein we
      describe the molecular and structural basis of TTR tetramer stabilization by
      tafamidis. Tafamidis binds selectively and with negative cooperativity (K(d)s ~2
      nM and ~200 nM) to the two normally unoccupied thyroxine-binding sites of the
      tetramer, and kinetically stabilizes TTR. Patient-derived amyloidogenic variants
      of TTR, including kinetically and thermodynamically less stable mutants, are also
      stabilized by tafamidis binding. The crystal structure of tafamidis-bound TTR
      suggests that binding stabilizes the weaker dimer-dimer interface against
      dissociation, the rate-limiting step of amyloidogenesis.

PMID- 22645361
TI  - Domain activities of PapC usher reveal the mechanism of action of an Escherichia
      coli molecular machine.
AB  - P pili are prototypical chaperone-usher pathway-assembled pili used by Gram
      negative bacteria to adhere to host tissues. The PapC usher contains five
      functional domains: a transmembrane beta-barrel, a beta-sandwich Plug, an N
      terminal (periplasmic) domain (NTD), and two C-terminal (periplasmic) domains,
      CTD1 and CTD2. Here, we delineated usher domain interactions between themselves
      and with chaperone-subunit complexes and showed that overexpression of individual
      usher domains inhibits pilus assembly. Prior work revealed that the Plug domain
      occludes the pore of the transmembrane domain of a solitary usher, but the
      chaperone-adhesin-bound usher has its Plug displaced from the pore, adjacent to
      the NTD. We demonstrate an interaction between the NTD and Plug domains that
      suggests a biophysical basis for usher gating. Furthermore, we found that the NTD
      exhibits high-affinity binding to the chaperone-adhesin (PapDG) complex and low
      affinity binding to the major tip subunit PapE (PapDE). We also demonstrate that
      CTD2 binds with lower affinity to all tested chaperone-subunit complexes except
      for the chaperone-terminator subunit (PapDH) and has a catalytic role in
      dissociating the NTD-PapDG complex, suggesting an interplay between recruitment
      to the NTD and transfer to CTD2 during pilus initiation. The Plug domain and the
      NTD-Plug complex bound all of the chaperone-subunit complexes tested including
      PapDH, suggesting that the Plug actively recruits chaperone-subunit complexes to
      the usher and is the sole recruiter of PapDH. Overall, our studies reveal the
      cooperative, active roles played by periplasmic domains of the usher to initiate,
      grow, and terminate a prototypical chaperone-usher pathway pilus.

PMID- 22645362
TI  - Homologous chromosomes make contact at the sites of double-strand breaks in genes
      in somatic G0/G1-phase human cells.
AB  - Double-strand DNA breaks (DSBs) are continuously induced in cells by endogenously
      generated free radicals and exogenous genotoxic agents such as ionizing
      radiation. DSBs activate the kinase activity in sensor proteins such as ATM and
      DNA-PK, initiating a complex DNA damage response that coordinates various DNA
      repair pathways to restore genomic integrity. In this study, we report the
      unexpected finding that homologous chromosomes contact each other at the sites of
      DSBs induced by either radiation or the endonuclease I-PpoI in human somatic
      cells. Contact involves short segments of homologous chromosomes and is centered
      on a DSB in active genes but does not occur at I-PpoI sites in intergenic DNA. I
      PpoI-induced contact between homologous genes is abrogated by the transcriptional
      inhibitors actinomycin D and alpha-amanitin and requires the kinase activity of
      ATM but not DNA-PK. Our findings provide documentation of a common transcription
      related and ATM kinase-dependent mechanism that induces contact between allelic
      regions of homologous chromosomes at sites of DSBs in human somatic cells.

PMID- 22645363
TI  - Autophagy regulates Wolbachia populations across diverse symbiotic associations.
AB  - Wolbachia are widespread and abundant intracellular symbionts of arthropods and
      filarial nematodes. Their symbiotic relationships encompass obligate mutualism,
      commensalism, parasitism, and pathogenicity. A consequence of these diverse
      associations is that Wolbachia encounter a wide range of host cells and
      intracellular immune defense mechanisms of invertebrates, which they must evade
      to maintain their populations and spread to new hosts. Here we show that
      autophagy, a conserved intracellular defense mechanism and regulator of cell
      homeostasis, is a major immune recognition and regulatory process that determines
      the size of Wolbachia populations. The regulation of Wolbachia populations by
      autophagy occurs across all distinct symbiotic relationships and can be
      manipulated either chemically or genetically to modulate the Wolbachia population
      load. The recognition and activation of host autophagy is particularly apparent
      in rapidly replicating strains of Wolbachia found in somatic tissues of
      Drosophila and filarial nematodes. In filarial nematodes, which host a
      mutualistic association with Wolbachia, the use of antibiotics such as
      doxycycline to eliminate Wolbachia has emerged as a promising approach to their
      treatment and control. Here we show that the activation of host nematode
      autophagy reduces bacterial loads to the same magnitude as antibiotic therapy;
      thus we identify a bactericidal mode of action targeting Wolbachia that can be
      exploited for the development of chemotherapeutic agents against onchocerciasis,
      lymphatic filariasis, and heartworm.

PMID- 22645364
TI  - Revealing the microscale spatial signature of dengue transmission and immunity in
      an urban population.
AB  - It is well-known that the distribution of immunity in a population dictates the
      future incidence of infectious disease, but this process is generally understood
      at individual or macroscales. For example, herd immunity to multiple pathogens
      has been observed at national and city levels. However, the effects of population
      immunity have not previously been shown at scales smaller than the city (e.g.,
      neighborhoods). In particular, no study has shown long-term effects of population
      immunity at scales consistent with the spatial scale of person-to-person
      transmission. Here, we use the location of dengue patients' homes in Bangkok with
      the serotype of the infecting pathogen to investigate the spatiotemporal
      distribution of disease risk at small spatial scales over a 5-y period. We find
      evidence for localized transmission at distances of under 1 km. We also observe
      patterns of spatiotemporal dependence consistent with the expected impacts of
      homotypic immunity, heterotypic immunity, and immune enhancement of disease at
      these distances. Our observations indicate that immunological memory of dengue
      serotypes occurs at the neighborhood level in this large urban setting. These
      methods have broad applications to studying the spatiotemporal structure of
      disease risk where pathogen serotype or genetic information is known.

PMID- 22645365
TI  - Floral humidity as a reliable sensory cue for profitability assessment by nectar
      foraging hawkmoths.
AB  - Most research on plant-pollinator communication has focused on sensory and
      behavioral responses to relatively static cues. Floral rewards such as nectar,
      however, are dynamic, and foraging animals will increase their energetic profit
      if they can make use of floral cues that more accurately indicate nectar
      availability. Here we document such a cue--transient humidity gradients--using
      the night blooming flowers of Oenothera cespitosa (Onagraceae). The headspace of
      newly opened flowers reaches levels of about 4% above ambient relative humidity
      due to additive evapotranspirational water loss through petals and water
      saturated air from the nectar tube. Floral humidity plumes differ from ambient
      levels only during the first 30 min after anthesis (before nectar is depleted in
      wild populations), whereas other floral traits (scent, shape, and color) persist
      for 12-24 h. Manipulative experiments indicated that floral humidity gradients
      are mechanistically linked to nectar volume and therefore contain information
      about energy rewards to floral visitors. Behavioral assays with Hyles lineata
      (Sphingidae) and artificial flowers with appropriate humidity gradients suggest
      that these hawkmoth pollinators distinguish between subtle differences in
      relative humidity when other floral cues are held constant. Moths consistently
      approached and probed flowers with elevated humidity over those with ambient
      humidity levels. Because floral humidity gradients are largely produced by the
      evaporation of nectar itself, they represent condition-informative cues that
      facilitate remote sensing of floral profitability by discriminating foragers. In
      a xeric environment, this level of honest communication should be adaptive when
      plant reproductive success is pollinator limited, due to intense competition for
      the attention of a specialized pollinator.

PMID- 22645366
TI  - Anti-Arrhenius cleavage of covalent bonds in bottlebrush macromolecules on
      substrate.
AB  - Spontaneous degradation of bottlebrush macromolecules on aqueous substrates was
      monitored by atomic force microscopy. Scission of C ? C covalent bonds in the
      brush backbone occurred due to steric repulsion between the adsorbed side chains,
      which generated bond tension on the order of several nano-Newtons. Unlike
      conventional chemical reactions, the rate of bond scission was shown to decrease
      with temperature. This apparent anti-Arrhenius behavior was caused by a decrease
      in the surface energy of the underlying substrate upon heating, which results in
      a corresponding decrease of bond tension in the adsorbed macromolecules. Even
      though the tension dropped minimally from 2.16 to 1.89 nN, this was sufficient to
      overpower the increase in the thermal energy (k(B)T) in the Arrhenius equation.
      The rate constant of the bond-scission reaction was measured as a function of
      temperature and surface energy. Fitting the experimental data by a perturbed
      Morse potential V = V(0)(1 - e(-betax))(2) - fx, we determined the depth and
      width of the potential to be V(0) = 141 +/- 19 kJ/mol and beta(-1) = 0.18 +/-
      0.03 A, respectively. Whereas the V(0) value is in reasonable agreement with the
      activation energy E(a) = 80-220 kJ/mol of mechanical and thermal degradation of
      organic polymers, it is significantly lower than the dissociation energy of a C ?
      C bond D(e) = 350 kJ/mol. Moreover, the force constant K(x) = 2beta(2)V(0) = 1.45
      +/- 0.36 kN/m of a strained bottlebrush along its backbone is markedly larger
      than the force constant of a C ? C bond K(l) = 0.44 kN/m, which is attributed to
      additional stiffness due to deformation of the side chains.

PMID- 22645367
TI  - Templates are available to model nearly all complexes of structurally
      characterized proteins.
AB  - Traditional approaches to protein-protein docking sample the binding modes with
      no regard to similar experimentally determined structures (templates) of protein
      protein complexes. Emerging template-based docking approaches utilize such
      similar complexes to determine the docking predictions. The docking problem
      assumes the knowledge of the participating proteins' structures. Thus, it
      provides the possibility of aligning the structures of the proteins and the
      template complexes. The progress in the development of template-based docking and
      the vast experience in template-based modeling of individual proteins show that,
      generally, such approaches are more reliable than the free modeling. The key
      aspect of this modeling paradigm is the availability of the templates. The
      current common perception is that due to the difficulties in experimental
      structure determination of protein-protein complexes, the pool of docking
      templates is insignificant, and thus a broad application of template-based
      docking is possible only at some future time. The results of our large scale,
      systematic study show that, surprisingly, in spite of the limited number of
      protein-protein complexes in the Protein Data Bank, docking templates can be
      found for complexes representing almost all the known protein-protein
      interactions, provided the components themselves have a known structure or can be
      homology-built. About one-third of the templates are of good quality when they
      are compared to experimental structures in test sets extracted from the Protein
      Data Bank and would be useful starting points in modeling the complexes. This
      finding dramatically expands our ability to model protein interactions, and has
      far-reaching implications for the protein docking field in general.

PMID- 22645368
TI  - Heart wall myofibers are arranged in minimal surfaces to optimize organ function.
AB  - Heart wall myofibers wind as helices around the ventricles, strengthening them in
      a manner analogous to the reinforcement of concrete cylindrical columns by spiral
      steel cables [Richart FE, et al. (1929) Univ of Illinois, Eng Exp Stn Bull 190].
      A multitude of such fibers, arranged smoothly and regularly, contract and relax
      as an integrated functional unit as the heart beats. To orchestrate this motion,
      fiber tangling must be avoided and pumping should be efficient. Current models of
      myofiber orientation across the heart wall suggest groupings into sheets or
      bands, but the precise geometry of bundles of myofibers is unknown. Here we show
      that this arrangement takes the form of a special minimal surface, the
      generalized helicoid [Blair DE, Vanstone JR (1978) Minimal Submanifolds and
      Geodesics 13-16], closing the gap between individual myofibers and their
      collective wall structure. The model holds across species, with a smooth
      variation in its three curvature parameters within the myocardial wall providing
      tight fits to diffusion magnetic resonance images from the rat, the dog, and the
      human. Mathematically it explains how myofibers are bundled in the heart wall
      while economizing fiber length and optimizing ventricular ejection volume as they
      contract. The generalized helicoid provides a unique foundation for analyzing the
      fibrous composite of the heart wall and should therefore find applications in
      heart tissue engineering and in the study of heart muscle diseases.

PMID- 22645369
TI  - Accurate de novo structure prediction of large transmembrane protein domains
      using fragment-assembly and correlated mutation analysis.
AB  - A new de novo protein structure prediction method for transmembrane proteins
      (FILM3) is described that is able to accurately predict the structures of large
      membrane proteins domains using an ensemble of two secondary structure prediction
      methods to guide fragment selection in combination with a scoring function based
      solely on correlated mutations detected in multiple sequence alignments. This
      approach has been validated by generating models for 28 membrane proteins with a
      diverse range of complex topologies and an average length of over 300 residues
      with results showing that TM-scores > 0.5 can be achieved in almost every case
      following refinement using MODELLER. In one of the most impressive results, a
      model of mitochondrial cytochrome c oxidase polypeptide I was obtained with a TM
      score > 0.75 and an rmsd of only 5.7 A over all 514 residues. These results
      suggest that FILM3 could be applicable to a wide range of transmembrane proteins
      of as-yet-unknown 3D structure given sufficient homologous sequences.

PMID- 22645370
TI  - Flexibility of the metal-binding region in apo-cupredoxins.
AB  - Protein-mediated electron transfer is an essential event in many biochemical
      processes. Efficient electron transfer requires the reorganization energy of the
      redox event to be minimized, which is ensured by the presence of rigid donor and
      acceptor sites. Electron transfer copper sites are present in the ubiquitous
      cupredoxin fold, able to bind one or two copper ions. The low reorganization
      energy in these metal centers has been accounted for by assuming that the protein
      scaffold creates an entatic/rack-induced state, which gives rise to a rigid
      environment by means of a preformed metal chelating site. However, this notion is
      incompatible with the need for an exposed metal-binding site and protein-protein
      interactions enabling metallochaperone-mediated assembly of the copper site. Here
      we report an NMR study that reveals a high degree of structural heterogeneity in
      the metal-binding region of the nonmetallated Cu(A)-binding cupredoxin domain,
      arising from microsecond to second dynamics that are quenched upon metal binding.
      We also report similar dynamic features in apo-azurin, a paradigmatic blue copper
      protein, suggesting a general behavior. These findings reveal that the
      entatic/rack-induced state, governing the features of the metal center in the
      copper-loaded protein, does not require a preformed metal-binding site. Instead,
      metal binding is a major contributor to the rigidity of electron transfer copper
      centers. These results reconcile the seemingly contradictory requirements of a
      rigid, occluded center for electron transfer, and an accessible, dynamic site
      required for in vivo copper uptake.

PMID- 22645371
TI  - Thermal modulation of birefringence observed in a crystalline molecular gyrotop.
AB  - Recently, functional organic materials have been put into practical use. The
      application of molecular motions has the potential to create new molecule-based
      materials. For this reason, considerable attention has been focused on the
      chemistry and properties of molecular machines in which mechanical motions of
      parts of the molecules are observed. In particular, phenylene rotation in the
      crystalline state has been investigated using framed molecular gyrotops having a
      phenylene rotor encased in three long alkyl spokes. In this study, we show
      thermal modulation of birefringence in a crystal due to the states of dynamic
      equilibrium of a novel molecular gyrotop. A macrocage molecule having a bridged
      phenylene rotor was synthesized as a novel molecular gyrotop. Rapid rotation of
      the phenylene rotor of the molecular gyrotop was confirmed by solid-state (2)H
      NMR spectroscopy that showed changes in the optical properties of a single
      crystal, i.e., the thermal modulation of birefringence. These results are the
      first application of the dynamic states in a crystal causing an optical change.
      These phenomena were also confirmed by control experiments using a molecular
      gyrotop with a nonrotating xylene rotor. We anticipate our finding to be a
      starting point for the creation of a new field of material chemistry that will
      make use of the dynamic states of molecules.

PMID- 22645372
TI  - Molecular interactions in the priming complex of bacteriophage T7.
AB  - The lagging-strand DNA polymerase requires an oligoribonucleotide, synthesized by
      DNA primase, to initiate the synthesis of an Okazaki fragment. In the replication
      system of bacteriophage T7 both DNA primase and DNA helicase activities are
      contained within a single protein, the bifunctional gene 4 protein (gp4).
      Intermolecular interactions between gp4 and T7 DNA polymerase are crucial for the
      stabilization of the oligoribonucleotide, its transfer to the polymerase, and its
      extension by DNA polymerase. We have identified conditions necessary to assemble
      the T7 priming complex and characterized its biophysical properties using
      fluorescence anisotropy. In order to reveal molecular interactions that occur
      during delivery of the oligoribonucleotide to DNA polymerase, we have used four
      genetically altered gp4 to demonstrate that both the RNA polymerase and the zinc
      finger domains of DNA primase are involved in the stabilization of the priming
      complex and in sequence recognition in the DNA template. We find that the
      helicase domain of gp4 contributes to the stability of the complex by binding to
      the ssDNA template. The C-terminal tail of gp4 is not required for complex
      formation.

PMID- 22645373
TI  - Electronic properties of nanoentities revealed by electrically driven rotation.
AB  - Direct electric measurement via small contacting pads on individual quasi-one
      dimensional nanoentities, such as nanowires and carbon nanotubes, are usually
      required to access its electronic properties. We show in this work that 1D
      nanoentities in suspension can be driven to rotation by AC electric fields. The
      chirality of the resultantrotation unambiguously reveals whether the nanoentities
      are metal, semiconductor, or insulator due to the dependence of the Clausius
      Mossotti factor on the material conductivity and frequency. This contactless
      method provides rapid and parallel identification of the electrical
      characteristics of 1D nanoentities.

PMID- 22645374
TI  - Hierarchical nanostructured conducting polymer hydrogel with high electrochemical
      activity.
AB  - Conducting polymer hydrogels represent a unique class of materials that
      synergizes the advantageous features of hydrogels and organic conductors and have
      been used in many applications such as bioelectronics and energy storage devices.
      They are often synthesized by polymerizing conductive polymer monomer within a
      nonconducting hydrogel matrix, resulting in deterioration of their electrical
      properties. Here, we report a scalable and versatile synthesis of multifunctional
      polyaniline (PAni) hydrogel with excellent electronic conductivity and
      electrochemical properties. With high surface area and three-dimensional porous
      nanostructures, the PAni hydrogels demonstrated potential as high-performance
      supercapacitor electrodes with high specific capacitance (~480 F.g(-1)),
      unprecedented rate capability, and cycling stability (~83% capacitance retention
      after 10,000 cycles). The PAni hydrogels can also function as the active
      component of glucose oxidase sensors with fast response time (~0.3 s) and
      superior sensitivity (~16.7 MUA . mM(-1)). The scalable synthesis and excellent
      electrode performance of the PAni hydrogel make it an attractive candidate for
      bioelectronics and future-generation energy storage electrodes.

PMID- 22645375
TI  - Fluvial landscapes of the Harappan civilization.
AB  - The collapse of the Bronze Age Harappan, one of the earliest urban civilizations,
      remains an enigma. Urbanism flourished in the western region of the Indo-Gangetic
      Plain for approximately 600 y, but since approximately 3,900 y ago, the total
      settled area and settlement sizes declined, many sites were abandoned, and a
      significant shift in site numbers and density towards the east is recorded. We
      report morphologic and chronologic evidence indicating that fluvial landscapes in
      Harappan territory became remarkably stable during the late Holocene as
      aridification intensified in the region after approximately 5,000 BP. Upstream on
      the alluvial plain, the large Himalayan rivers in Punjab stopped incising, while
      downstream, sedimentation slowed on the distinctive mega-fluvial ridge, which the
      Indus built in Sindh. This fluvial quiescence suggests a gradual decrease in
      flood intensity that probably stimulated intensive agriculture initially and
      encouraged urbanization around 4,500 BP. However, further decline in monsoon
      precipitation led to conditions adverse to both inundation- and rain-based
      farming. Contrary to earlier assumptions that a large glacier-fed Himalayan
      river, identified by some with the mythical Sarasvati, watered the Harappan
      heartland on the interfluve between the Indus and Ganges basins, we show that
      only monsoonal-fed rivers were active there during the Holocene. As the monsoon
      weakened, monsoonal rivers gradually dried or became seasonal, affecting
      habitability along their courses. Hydroclimatic stress increased the
      vulnerability of agricultural production supporting Harappan urbanism, leading to
      settlement downsizing, diversification of crops, and a drastic increase in
      settlements in the moister monsoon regions of the upper Punjab, Haryana, and
      Uttar Pradesh.

PMID- 22645377
TI  - Fructose as a significant cause of gout is unfounded and premature.

PMID- 22645378
TI  - Cardioembolic stroke following a fractured transseptal wire.

PMID- 22645376
TI  - In vitro microvessels for the study of angiogenesis and thrombosis.
AB  - Microvascular networks support metabolic activity and define microenvironmental
      conditions within tissues in health and pathology. Recapitulation of functional
      microvascular structures in vitro could provide a platform for the study of
      complex vascular phenomena, including angiogenesis and thrombosis. We have
      engineered living microvascular networks in three-dimensional tissue scaffolds
      and demonstrated their biofunctionality in vitro. We describe the lithographic
      technique used to form endothelialized microfluidic vessels within a native
      collagen matrix; we characterize the morphology, mass transfer processes, and
      long-term stability of the endothelium; we elucidate the angiogenic activities of
      the endothelia and differential interactions with perivascular cells seeded in
      the collagen bulk; and we demonstrate the nonthrombotic nature of the vascular
      endothelium and its transition to a prothrombotic state during an inflammatory
      response. The success of these microvascular networks in recapitulating these
      phenomena points to the broad potential of this platform for the study of
      cardiovascular biology and pathophysiology.

PMID- 22645379
TI  - Incorporating global features of RNA motifs in predictions for an ensemble of
      secondary structures for encapsidated MS2 bacteriophage RNA.
AB  - The secondary structure of encapsidated MS2 genomic RNA poses an interesting RNA
      folding challenge. Cryoelectron microscopy has demonstrated that encapsidated MS2
      RNA is well-ordered. Models of MS2 assembly suggest that the RNA hairpin-protein
      interactions and the appropriate placement of hairpins in the MS2 RNA secondary
      structure can guide the formation of the correct icosahedral particle. The RNA
      hairpin motif that is recognized by the MS2 capsid protein dimers, however, is
      energetically unfavorable, and thus free energy predictions are biased against
      this motif. Computer programs called Crumple, Sliding Windows, and Assembly
      provide useful tools for prediction of viral RNA secondary structures when the
      traditional assumptions of RNA structure prediction by free energy minimization
      may not apply. These methods allow incorporation of global features of the RNA
      fold and motifs that are difficult to include directly in minimum free energy
      predictions. For example, with MS2 RNA the experimental data from SELEX
      experiments, crystallography, and theoretical calculations of the path for the
      series of hairpins can be incorporated in the RNA structure prediction, and thus
      the influence of free energy considerations can be modulated. This approach
      thoroughly explores conformational space and generates an ensemble of secondary
      structures. The predictions from this new approach can test hypotheses and models
      of viral assembly and guide construction of complete three-dimensional models of
      virus particles.

PMID- 22645380
TI  - RNASTAR: an RNA STructural Alignment Repository that provides insight into the
      evolution of natural and artificial RNAs.
AB  - Automated RNA alignment algorithms often fail to recapture the essential
      conserved sites that are critical for function. To assist in the refinement of
      these algorithms, we manually curated a set of 148 alignments with a total of
      9600 unique sequences, in which each alignment was backed by at least one crystal
      or NMR structure. These alignments included both naturally and artificially
      selected molecules. We used principles of isostericity to improve the alignments
      from an average of 83%-94% isosteric base pairs. We expect that this alignment
      collection will assist in a wide range of benchmarking efforts and provide new
      insight into evolutionary principles governing change in RNA structural motifs.
      The improved alignments have been contributed to the Rfam database.

PMID- 22645381
TI  - Estimation of specific absorbed fractions for selected organs due to photons
      emitted by activity deposited in the human respiratory tract using ICRP/ICRU male
      voxel phantom in FLUKA.
AB  - The ICRP/ICRU adult male reference voxel phantom incorporated in Monte Carlo code
      FLUKA is used for estimating specific absorbed fractions (SAFs) for photons due
      to the presence of internal radioactive contamination in the human respiratory
      tract (RT). The compartments of the RT, i.e. extrathoracic (ET1 and ET2) and
      thoracic (bronchi, bronchioles, alveolar interstitial) regions, lymph nodes of
      both regions and lungs are considered as the source organs. The nine organs
      having high tissue weighting factors such as colon, lungs, stomach wall, breast,
      testis, urinary bladder, oesophagus, liver and thyroid and the compartments of
      the RT are considered as target organs. Eleven photon energies in the range of 15
      keV to 4 MeV are considered for each source organ and the computed SAF values are
      presented in the form of tables. For the target organs in the proximity of the
      source organ including the source organ itself, the SAF values are relatively
      higher and decrease with increase in energy. As the distance between source and
      target organ increases, SAF values increase with energy and reach maxima
      depending on the position of the target organ with respect to the source organ.
      The SAF values are relatively higher for the target organs with smaller masses.
      Large deviations are seen in computed SAF values from the existing MIRD phantom
      data for most of the organs. These estimated SAF values play an important role in
      the estimation of equivalent dose to various target organs of a worker due to
      intake by inhalation pathway.

PMID- 22645382
TI  - Mass attenuation coefficients, effective atomic numbers and effective electron
      densities for some polymers.
AB  - In this study, the total mass attenuation coefficients (MU(m)) for some homo- and
      hetero-chain polymers, namely polyamide-6 (PA-6), poly-methyl methacrylate
      (PMMA), low-density polyethylene (LDPE), polypropylene (PP) and polystyrene (PS)
      were measured at 59.5, 511, 661.6, 1173.2, 1274.5 and 1332.5 keV photon energies.
      The samples were separately irradiated with (241)Am, (22)Na, (137)Cs and (60)Co
      (638 kBq) radioactive gamma sources. The measurements were made by performing
      transmission experiments with a 2"*2" NaI(Tl) scintillation detector having an
      energy resolution of 7 % at 662 keV gamma ray from the decay of (137)Cs. The
      effective atomic numbers (Z(eff)) and the effective electron densities (N(eff))
      were determined experimentally and theoretically using the obtained MU(m) values
      for the investigated samples. Furthermore, Z(eff) and N(eff) of each polymer were
      computed for total photon interaction cross-sections using theoretical data over
      a wide energy region from 1 keV to 10 MeV. The experimental values of the
      selected polymers were found to be in good agreement with the theoretical values.

PMID- 22645383
TI  - Comparison of radiation doses between newborns and 6-y-old children undergoing
      head, chest and abdominal CT examinations: a phantom study.
AB  - Radiation doses in paediatric computed tomography (CT) were investigated for
      various types of recent CT scanners with newborn and 6-y-old phantoms in which
      silicon-photodiode dosemeters were implanted at various organ positions. In the
      head, chest and abdominal CT for the newborn phantom, doses for organs within the
      scan region were 21-40, 3-8 and 3-12 mGy, respectively. The corresponding doses
      for the child phantom were 20-37, 2-11 and 4-17 mGy, respectively. In the head,
      chest and abdominal CT, the effective doses were respectively 2.1-3.3, 2.0-6.0
      and 2.2-10.0 mSv for the newborn, and 1.0-2.0, 1.2-6.6 and 2.9-11.8 mSv for the
      child. Radiation doses for the newborn were at the same levels as those for the
      child, excepting effective doses in head CT for the newborn, which were 1.8 times
      higher than those for the child.

PMID- 22645384
TI  - The investigation of radionuclide distributions in soil samples collected from
      Bursa, Turkey.
AB  - The distributions of (226)Ra, (232)Th, (40)K and (137)Cs activity concentrations
      were determined using a high-purity germanium detector in uncultivated surface
      soil samples collected from Bursa. The range of (226)Ra, (232)Th, (40)K and
      (137)Cs activity concentrations varied from 10+/-1 to 61+/-3 Bq kg(-1) (mean
      value 25+/-3 Bq kg(-1)), from 12+/-1 to 50+/-2 Bq kg(-1) (mean value 26+/-3 Bq
      kg(-1)), from 257+/-5 to 1010+/-11 Bq kg(-1) (mean value 435+/-44 Bq kg(-1)) and
      from 1.01+/-0.07 to 48.97+/-0.54 Bq kg(-1) (mean value 8.52+/-2.59 Bq kg(-1)),
      respectively. In addition, the mean outdoor absorbed dose rates in air, annual
      effective dose equivalent, radium equivalent activity and external hazard index
      were found to be 45 nGy h(-1), 56 MUSv y(-1), 96 Bq kg(-1) and 0.26,
      respectively. The gross beta activity concentrations were determined using a
      Tennelec LB 1000-PW detector. The range of gross beta activity concentrations
      varied from 46+/-9 to 1199+/-113 Bq kg(-1) with a mean value of 541+/-19 Bq kg(
      1).

PMID- 22645385
TI  - Calculation of patient effective dose and scattered dose for dental mobile
      fluoroscopic equipment: application of the Monte Carlo simulation.
AB  - The objective of this study was to evaluate the patient effective dose and
      scattered dose from recently developed dental mobile equipment in Korea. The
      MCNPX 2.6 (Los Alamos National Laboratory, USA) was used in a Monte Carlo
      simulation to calculate both the effective and scattered doses. The MCNPX code
      was constructed identically as in the general use of equipment and the effective
      dose and scattered dose were calculated using the KTMAN-2 digital phantom. The
      effective dose was calculated as 906 MUSv. The equivalent doses per organ were
      calculated via the MCNPX code, and were 32 174 and 19 MUSv in the salivary gland
      and oesophagus, respectively. The scattered dose of 22.5-32.6 MUSv of the tube
      side at 25 cm from the centre in anterior and posterior planes was measured as
      1.4-3 times higher than the detector side of 10.5-16.0 MUSv.

PMID- 22645386
TI  - Doses and risks from uranium are not increased significantly by interactions with
      natural background photon radiation.
AB  - The impact of depleted uranium (DU) on human health has been the subject of much
      conjecture. Both the chemical and radiological aspects of its behaviour in the
      human body have previously been investigated in detail, with the radiological
      impact being assumed to be linked to the alpha decay of uranium. More recently,
      it has been proposed that the accumulation in tissue of high-Z materials, such as
      DU, may give rise to enhanced local energy deposition in the presence of natural
      background photon radiation due to the high photoelectric interaction cross
      sections of high-Z atoms. It is speculated that, in addition to producing short
      range photoelectrons, these events will be followed by intense Auger and Coster
      Kronig electron emission, thereby causing levels of cell damage that are
      unaccounted for in conventional models of radiological risk. In this study, the
      physical and biological bases of these claims are investigated. The potential
      magnitudes of any effect are evaluated and discussed, and compared with the risks
      from other radiological or chemical hazards. Monte Carlo calculations are
      performed to estimate likely energy depositions due to the presence of uranium in
      human tissues in photon fields: whole body doses, organ doses in anthropomorphic
      phantoms and nano-/micro-dosimetric scenarios are each considered. The proposal
      is shown generally to be based on sound physics, but overall the impact on human
      health is expected to be negligible.

PMID- 22645387
TI  - Influence of age on the association of GIRK4 with metabolic syndrome.
AB  - BACKGROUND: G protein-coupled inward rectifier K+ channel 4 (GIRK4) gene
      expressions have been implicated in the development of obesity, a key feature of
      metabolic syndrome (MetS). We investigated whether sequence variants of GIRK4 may
      represent metabolic risk factors for the Uygur Chinese population. METHODS: The
      entire GIRK4 gene, including all exons, the promoter and untranslated regions
      from 48 MetS individuals, was studied in order to identify genetic variations
      associated with the disorder. Targeted genotyping of four common single
      nucleotide polymorphisms (SNPs: rs11221497, rs6590357, rs4937391 and rs2604204)
      and one novel missense mutation (M210I) was performed using the TaqMan polymerase
      chain reaction method for 443 MetS and 786 non-MetS subjects. RESULTS: When all
      MetS cases were compared against all non-MetS controls, no significant
      association was found between the three SNPs (rs2604204, rs4937391 and rs6590357)
      and MetS status or metabolic traits. After adjustment, rs11221497 was associated
      with MetS (odds ratio (OR) [95% CI]=0.731 [0.551-0.968], P=0.029). Interestingly,
      when the MetS group was stratified into subclasses by age, an association was
      found for the three SNPs (rs2604204, rs4937391 and rs6590357) having estimated
      false discovery rates<0.001 and age of <50 y. After adjustment, the SNPs
      rs2604204, rs4937391 and rs6590357 were also associated with MetS in younger
      subjects: ORs [95% CI]: 1.678 [1.149-2.450], 1.839 [1.204-2.809] and 0.602 [0.379
      0.958], respectively. All of the four SNPs showed a trend towards lower or higher
      metabolic traits (P<0.05) in younger subjects. In addition, a newly identified
      missense mutation (M210I) was not specifically related with MetS. CONCLUSIONS:
      GIRK4 sequence variants appear to associate with MetS in the Uygurian population,
      and this association may be influenced by age.

PMID- 22645388
TI  - Interference in the autoDELFIAR hAFP immunoassay and effect on second-trimester
      Down's syndrome screening.

PMID- 22645389
TI  - Meta-analysis on COPD: comment on 'Home telehealth for chronic obstructive
      pulmonary disease: a systematic review and meta-analysis. by J Polisena et al.'.

PMID- 22645390
TI  - Understanding trends in genital Chlamydia trachomatis can benefit from enhanced
      surveillance: findings from Australia.
AB  - OBJECTIVES: To determine trends and correlates of chlamydia positivity among
      young heterosexuals attending Australian sexual health services and to compare
      these with population-based notification data. METHODS: Data from 18 sexual
      health services and the national notification scheme were analysed. A chi2 test
      assessed trends in chlamydia positivity among young heterosexuals tested from
      2006 to 2010, and logistic regression was used to determine correlates of
      positivity. Nucleic acid amplification tests were used throughout the study
      period. RESULTS: During 2006-2010, 64 588 heterosexuals aged 15-29 years attended
      the sexual health services for the first time and the annual chlamydia testing
      rate was consistently >80%. Overall, chlamydia positivity increased by 12%, by
      8.3% in heterosexual men (from 13.2% in 2006 to 14.3% in 2010; p-trend=0.04) and
      by 15.9% in women (from 11.3% in 2006 to 13.1% in 2010; p-trend<0.01).
      Independent correlates of chlamydia positivity in sexual health service patients
      were being aged 15-24 years, residing in a regional/rural area, being Aboriginal
      and/or Torres Strait Islander, being a non-Australian resident and attending in
      2010 compared with 2006. Over the same period, the population-based notification
      rate increased by 43% against a background of a >100% increase in testing.
      CONCLUSIONS: The sexual health service network suggests a moderate increase in
      chlamydia prevalence in young heterosexuals tested at sexual health services, in
      contrast to the steep increase shown by notifications. This highlights the
      caution needed in interpreting chlamydia trends without a corresponding testing
      denominator.

PMID- 22645391
TI  - A cross-sectional study on the acceptability of self-collection for HPV testing
      among women in rural China.
AB  - OBJECTIVE: To assess the acceptability of using self-collection as a method of
      sampling for human papilloma virus testing in rural China. METHODS: 174 women
      from the national cervical cancer screening programme in Xiangyuan County, China,
      were enrolled in our study and underwent self-collection, clinician collection,
      colposcopy examination and were administered questionnaire. The questionnaire
      assessed the patients' preference and acceptability of collection method.
      RESULTS: The mean overall acceptability score for self-collection, although
      significantly less than the overall score for clinician collection (p<0.01),
      still is well above 4 (4.33 of 5), indicating high acceptability. The
      acceptability scores for self-collection and clinician collection were not
      significantly different on scales measuring comfort and convenience (p>0.05). The
      scores were significantly lower for self-collection on scales measuring trust,
      ability to collect specimen and perceived effects of testing compared with
      clinician collection (p<0.01). 74% of participants preferred clinician
      collection, and of these participants, 86% preferred it because they thought the
      results were more accurate. CONCLUSIONS: The study shows that self-collection was
      highly acceptable and that self-collection and clinician collection were equally
      comfortable and convenient; however, the participants still preferred clinician
      collection because of lack of trust in the results of self-collection. This
      indicates that self-collection is an acceptable potential method for screening
      but education programmes about the validity of self-collection that target
      general population may be needed prior to implementation.

PMID- 22645392
TI  - Secondary syphilis mimicking inflammatory bowel disease.
AB  - This study reports the case of a 15-year-old male patient with extensive anal
      inflammation, cobblestone-like mucosa and areas of ulceration, loose bloody stool
      and weight loss for 8 weeks, suggestive of inflammatory bowel disease. Genital
      lesions of syphilides were later observed and Venereal Disease Research
      Laboratory test was positive, thus benzyl penicillin treatment was prescribed
      with total resolution of genital and bowel symptoms.

PMID- 22645394
TI  - Patients' views on failure to gain expected clinical beneficial outcomes from
      participation in palliative medicine clinical trials.
AB  - REASON FOR THE STUDY: This study aims to understand patients' views on failing to
      gain expected beneficial outcomes from palliative medicine clinical trials. This
      is a qualitative study involving semistructured interviews. MAIN FINDINGS: Seven
      patients were interviewed. Despite loss of initial hope in benefiting themselves
      in terms of better disease or symptom control, patients interviewed still found
      joining clinical trials meaningful experience in terms of benefiting future
      patients and being valuable life experience. Experience in interacting with
      research staff partly formulated final impressions on clinical trial
      participation experience. PRINCIPAL CONCLUSIONS: Joining well-designed clinical
      trials unlikely causes harm to patients. Caring attitudes of researchers and
      maintaining good researcher-patient relationships can help patients in meaning
      finding process, especially if they have failed to gain anticipated clinical
      benefits.

PMID- 22645393
TI  - Quality of life valuations of HPV-associated cancer health states by the general
      population.
AB  - OBJECTIVES: To obtain health-related quality of life valuations (ie, utilities)
      for human papillomavirus (HPV)-related cancer health states of vulval, vaginal,
      penile, anal and oropharyngeal cancers for use in modelling cost-effectiveness of
      prophylactic HPV vaccination. METHODS: Written case descriptions of each HPV
      associated cancer describing the 'average' patient surviving after the initial
      cancer diagnosis and treatment were developed in consultation with oncology
      clinicians. A general overview, standard gamble questionnaire for each health
      state and a quiz was conducted in 120 participants recruited from the general
      population. RESULTS: In the included population sample (n=99), the average age
      was 43 years (range = 18-70 years) with 54% men, 44% never married/43% married,
      76% education beyond year 12 and 39% employed full-time. The utility values for
      the five health states were 0.57 (95% CI 0.52 to 0.62) for anal cancer, 0.58
      (0.53 to 0.63) for oropharyngeal cancer, 0.59 (0.54 to 0.64) for vaginal cancer,
      0.65 (0.60 to 0.70) for vulval cancer and 0.79 (0.74 to 0.84) for penile cancer.
      Participants demonstrated a very good understanding of the symptoms, diagnosis
      and treatment of these cancers with a mean score of 9 (SD=1.1) on a 10-item quiz.
      CONCLUSIONS: This study provides utility estimates for the specific HPV-related
      cancers of vulval, vaginal, penile, anal and oropharyngeal cancers valued by a
      general population sample using standard gamble. The results demonstrate
      considerable quality of life impact associated with surviving these cancers that
      will be important to incorporate into modelling cost-effectiveness of
      prophylactic HPV vaccination in different populations.

PMID- 22645395
TI  - Understanding the social costs of psychosis: the experience of adults affected by
      psychosis identified within the second Australian National Survey of Psychosis.
AB  - BACKGROUND: Social inclusion is a key priority of the Fourth National Mental
      Health Plan for Australia (2009-2014), with strong evidence for its protective
      impact on mental health. Social integration has been associated with enhanced
      well-being for people with mental illnesses such as psychosis. OBJECTIVE: To
      explore the impact of psychosis on an individual's social and community
      participation. METHOD: The second Australian national survey of psychosis was
      conducted across seven Australian sites. Semi-structured interviews with adults
      living with psychosis assessed mental health status, social and role functioning,
      life satisfaction and future goals. The cohort comprised 1825 adults with a
      psychotic illness (59.6% were male; 42.4% were aged 18-34 years; 31.5% had 12
      years or more of education) of whom 32.7% had been employed in the past year.
      RESULTS: Most adults indicated experiencing loneliness (80.1%) and a need for
      more friends (48.1%). Men were more likely to have never had a long-term
      relationship (59.4% M, 33.2% F). Even though women were more likely to experience
      anxiety in social situations [(chi(2)(1) = 8.95, p < 0.01)], they were more
      likely to have attended a social activity in the past year [chi(2)(2) = 11.84, p
      < 0.01]. Just over half of the survey participants (56.7%) reported having daily
      or nearly daily contact with family members. In the past year, 69% had not
      attended any social activity and 43% described stigma as a barrier. Although
      63.2% showed significant impairment in social functioning, only 29.5% had
      received help for this in the last year. Social isolation and loneliness were
      rated as major challenges by 37.2% of the cohort. CONCLUSIONS: Social isolation
      and dysfunction experienced by people with psychosis have not decreased since the
      last Australian national survey of people with psychosis. Alongside education and
      employment, social functioning and participation must be addressed to improve
      social inclusion for people with psychosis. Programs targeting social
      opportunities (befriending, peer support), social anxiety and social functioning
      for all stages of psychosis are warranted.

PMID- 22645396
TI  - Tobacco smoking among people living with a psychotic illness: the second
      Australian Survey of Psychosis.
AB  - OBJECTIVE: The aims of this study were to (a) describe patterns of tobacco
      smoking among Australians living with a psychotic illness and (b) explore the
      association between smoking and measures of psychopathology, psychiatric history,
      psychosocial functioning, physical health, substance use and demographic
      characteristics. METHODS: Data were from 1812 participants in the 2010 Australian
      Survey of High Impact Psychosis. Participants were aged 18-64 years and resided
      in seven mental health catchment sites across five states of Australia. Bivariate
      statistics were used to compare smokers with non-smokers on the measures of
      interest, and to compare ICD-10 diagnostic categories on measures of smoking
      prevalence, nicotine addiction and quitting history. Multivariate logistic
      regression was used to test whether (a) demographics and psychiatric history were
      associated with having ever smoked and (b) whether symptoms and psychosocial
      functioning were independently associated with current smoking, after controlling
      for demographics, psychiatric history and substance use. RESULTS: The prevalence
      of current tobacco smoking was 66.6% (72% of men and 59% of women); lifetime
      prevalence was 81%. In univariate analyses, individuals with a diagnosis of
      schizophrenia or schizoaffective disorder were most likely to be smoking tobacco
      (70%) and were more nicotine dependent. Smokers reported worse perceived physical
      health, lower body mass index and waist circumference, and more lifetime medical
      conditions. A younger age of illness onset, male gender and low education were
      associated with having ever smoked. Associations with current smoking included
      low education, male gender, no formal employment, worse negative symptoms, higher
      daily caffeine consumption, and alcohol dependence and substance
      abuse/dependence. CONCLUSIONS: The prevalence of tobacco smoking is high amongst
      people with a psychotic disorder, and is associated with adverse mental health
      symptoms as well as high rates of other substance use, poorer subjective physical
      health, and a higher risk of the many known health consequences of smoking.

PMID- 22645397
TI  - Depression and 5-year mortality in patients with acute myocardial infarction:
      analysis of the IDACC database.
AB  - OBJECTIVE: Symptoms of depression are highly prevalent and persistent following
      myocardial infarction (MI). Whether depression is a risk factor for long-term
      mortality following MI remains controversial. The present study aimed to
      determine whether depression during hospitalisation for acute MI (AMI) predicted
      5-year all-cause or cardiac mortality. METHOD: This study utilised the
      Identifying Depression as a Comorbid Condition (IDACC) database of 337
      hospitalised patients with AMI. Depressive symptoms were assessed using the
      Center for Epidemiologic Studies Depression scale (CES-D). Data were linked to a
      government administrative death registry to determine 5-year mortality. Survival
      data were analysed using Cox's proportional hazards model. RESULTS: The mean age
      during AMI hospitalisation was 59 years +/- 12, 74% of patients were men and
      depression (CES-D >= 16) was present in 132 patients (39.3%). The 5-year all
      cause mortality rate was 10.4% (35 deaths) and the cardiac mortality rate was
      6.5% (22 deaths). When depression was defined as a dichotomous variable, moderate
      to severe depression (defined by CES-D >= 27) at the time of AMI was associated
      with all-cause mortality (hazard ratio 2.54, 95% confidence interval 1.03 to
      6.28; p = 0.04) but not cardiac mortality. However, when depression was defined
      by three categories (no depression CES-D < 16, mild depression CES-D 16-26,
      moderate to severe depression CES-D >= 27), it was not found to predict
      mortality. In addition, perceived social support was a predictor of all-cause and
      cardiac mortality in AMI patients. CONCLUSIONS: Our results indicate that the
      relationship between mortality and depression severity is not linear and that the
      association only becomes evident when the severity reaches a threshold level of
      CES-D >= 27, consistent with major depression. Low power may have influenced the
      finding of a lack of association between depression and cardiac mortality.

PMID- 22645398
TI  - Moving beyond the intensive behavior treatment versus eclectic dichotomy:
      evidence-based and individualized programs for learners with ASD.
AB  - Professionals serving students with autism spectrum disorders (ASD) in inclusive
      classroom settings face the challenge of selecting and successfully implementing
      evidence-based intervention strategies. Many propose that Intensive Behavioral
      Treatment (IBT) is the most efficacious approach for learners with ASD. Evidence
      for this approach is often established by comparing the IBT model to a condition
      described as "eclectic". In this paper, authors examine the IBT vs. eclectic
      literature, acknowledge the potential efficacy of the IBT model with preschool
      aged children, suggest concerns about efficacy studies that have compared IBT and
      eclectic programs, point out that most of the studies were restricted in the age
      range of their participants, and note that few were implemented in inclusive
      settings. The authors propose that a technical eclectic approach can be
      beneficial for children and youth with ASD if it is conceptually grounded,
      incorporates evidence-based focused intervention practices, and is well
      implemented. A detailed example of such a technical eclectic program model is
      provided and the practicality of such an approach in inclusive settings for
      children and youth with ASD and their families is discussed.

PMID- 22645399
TI  - Improving generalization of peer socialization gains in inclusive school settings
      using initiations training.
AB  - Social engagement by children with autism spectrum disorder (ASD) in unstructured
      school settings generally occurs at very low levels, if at all. Although many
      interventions improve peer socialization, generalization and maintenance of such
      gains when interventions are faded are typically low. The present study employed
      a multiple baseline design across participants to target generalization in the
      absence of interventionists in elementary school children with ASD at recess.
      Teaching initiations has been suggested as one method to increase generalization.
      The results of the present study showed that when initiations were targeted
      during intervention for social play, the participants demonstrated generalized
      peer social engagement, increases in unprompted peer-directed initiations, and
      more positive affect during peer interactions. Results are discussed in terms of
      theoretical and applied implications of incorporating initiations training into
      social interventions.

PMID- 22645400
TI  - Video-mediated communication to support distant family connectedness.
AB  - It can be difficult to maintain family connections with geographically distant
      members. However, advances in computer-human interaction (CHI) systems, including
      video-mediated communication (VMC) are emerging. While VMC does not completely
      substitute for physical face-to-face communication, it appears to provide a sense
      of virtual copresence through the addition of visual and contextual cues to
      verbal communication between family members. The purpose of this study was to
      explore current patterns of VMC use, experiences, and family functioning among
      self-identified VMC users separated geographically from their families. A total
      of 341 participants (ages 18 to above 70) completed an online survey and Family
      APGAR. Ninty-six percent of the participants reported that VMC was the most
      common communication method used and 60% used VMC at least once/week. The most
      common reason cited for using VMC over other methods of communication was the
      addition of visual cues. A significant difference between the Family APGAR scores
      and the number of positive comments about VMC experience was also found. This
      exploratory study provides insight into the acceptance of VMC and its usefulness
      in maintaining connections with distant family members.

PMID- 22645401
TI  - Regional evidence-based practice fellowship program: impact on evidence-based
      practice implementation and barriers.
AB  - This quasi-experimental, pre- and posttest study evaluated the impact of a 9
      month collaborative regional evidence-based practice (EBP) fellowship program on
      practice, attitude, knowledge, and perceived barriers associated with
      implementation of EBP. Three annual cohorts (N=142) of nurses attending a
      fellowship program from 2008 to 2010 participated in this study. Paired t tests
      showed statistically significant increases in practice (+.82; p<.001) and
      knowledge/skills (+.78; p<.001) associated with EBP, but showed no change in
      attitude (+.16; p=.198). All four Barriers subscales showed statistically
      significant decreases (-.10 to -.31; p=.036 to <.001). Hierarchical multiple
      regression analyses showed that the barriers explained 6.8%, 8.9% and 13.9% of
      variances in practice, attitude and knowledge/skills, respectively. The
      collaborative regional fellowship program improved the practice and
      knowledge/skills associated with EBP. The barriers were significant predictors of
      the EBP implementation among the targeted group of nurses participating in the
      fellowship program.

PMID- 22645402
TI  - ICD deactivation: review of literature and clinical recommendations.
AB  - Implanted cardioverter defibrillators (ICDs) are an essential part of the
      management for patients at risk for life threatening arrhythmias. Despite new
      technologies, all patients ultimately will reach the end of their lives, either
      because of underlying cardiac disease or another terminal illness. Having an ICD
      at the end of life may deny a patient the chance of sudden cardiac death and
      result in a slower terminal disease and pain and anxiety due to shocks from their
      device. The purpose of this article is to present a focused literature review on
      the barriers surrounding deactivation of ICDs and to summarize the
      recommendations of the Heart Rhythm Society Consensus Statement on the management
      of ICDs in patients nearing end of life or requesting withdrawal of therapy.

PMID- 22645403
TI  - Making sense of skin color in clinical care.
AB  - The background of this article is that assessment and quantification of skin
      color is important to health care; color is one indicator of overall health and
      is linked to oxygenation, tissue perfusion, nutritional status, and injury. The
      purpose is to describe how skin color varies across racial/ethnic groups so that
      the information can be applied to clinical practice. The method used is cross
      sectional, descriptive design (n = 257). We recorded self-defined race/ethnicity
      and used a spectrophotometer to measure skin color at two anatomic sites. Skin
      color variables included L* (light/dark), a* (red/green), and b* (yellow/blue).
      As regards results, we found significant differences in L*, a*, and b* values by
      site and race/ethnicity in White, Asian, and Biracial participants. L*: F(3, 233)
      = 139.04, p < .01 and F(3, 233) = 118.47, p < .01. Black participants had
      significantly lower mean L* values and wider ranges of L*, a*, and b* as compared
      with other groups. In regard to application, these findings suggest that
      clinicians and researchers should plan and provide care based on skin color,
      rather than race/ethnicity.

PMID- 22645404
TI  - The role of a new arrhythmia specialist nurse in providing support to patients
      and caregivers.
AB  - In 2005, the English Department of Health developed a National Service Framework
      for the identification and treatment of Arrhythmia. A new specialist role was
      recommended, the Arrhythmia Care Co-ordinator (ACC), to guide patients through
      their illness and coordinate their care. In 2006, to implement this policy, the
      British Heart Foundation (BHF) sponsored 32 new nursing ACC staff posts across
      England and Wales. The BHF also sponsored an evaluation to investigate the impact
      of ACC support on patients and caregivers, with 30 patients (18 men, 22 women)
      and 10 caregivers being drawn from a purposive sample across seven arrhythmia
      treatment centres. Two main key themes emerged to describe the patients'
      experience of the new service: personalized coordinated care and learning to live
      with their condition.

PMID- 22645405
TI  - A new model for integrated heart failure and palliative advanced homecare-
      rationale and design of a prospective randomized study.
AB  - BACKGROUND: Guidelines have concluded that there is a great need for new models
      of integrated care, e.g., heart failure and palliative care, in order to
      facilitate equality of care for dying patients, regardless of diagnosis. We found
      no evidence in the literature concerning the advantages and effects of integrated
      heart failure and palliative advanced home care for patients with severe chronic
      heart failure. AIM: The primary aim is to study the effects of integrated
      Palliative advanced homecarRE and heart FailurE caRE (PREFER) on patients'
      symptom burden, quality of life, and activities of daily living (ADL) as compared
      to usual care. METHOD: Prospective, randomized study with an open-evaluation
      PROBE design. Optimally treated outpatients with chronic heart failure of varying
      aetiologies in New York Heart Association classes III-IV will be eligible to
      participate. CONCLUSION: The PREFER study is designed to investigate whether a
      new concept of managing patients with severe chronic heart failure by integrating
      palliative homecare and active heart failure treatment will reduce symptom
      burden, increase quality of life and ADL, and reduce the number of
      hospitalizations in patients with severe chronic heart failure.

PMID- 22645406
TI  - Bile duct leaks from the intrahepatic biliary tree: a review of its etiology,
      incidence, and management.
AB  - Bile leaks from the intrahepatic biliary tree are an important cause of morbidity
      following hepatic surgery and trauma. Despite reduction in mortality for hepatic
      surgery in the last 2 decades, bile leaks rates have not changed significantly.
      In addition to posted operative bile leaks, leaks may occur following drainage of
      liver abscess and tumor ablation. Most bile leaks from the intrahepatic biliary
      tree are transient and managed conservatively by drainage alone or endoscopic
      biliary decompression. Selected cases may require reoperation and enteric
      drainage or liver resection for management.

PMID- 22645408
TI  - Association between high-sensitivity C-reactive protein and N-Terminal Pro-B-Type
      Natriuretic Peptide in patients with hepatitis C virus infection.
AB  - BACKGROUND: Prior study showed HCV-infected patients have increased serum N
      Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and a possible left
      ventricular diastolic dysfunction. The objectives of the present paper were to
      investigate the characteristics of hs-CRP and its correlation with clinical
      profiles including NT-proBNP and echocardiographic variables in HCV-infected
      patients. METHODS AND RESULTS: A total of 106 HCV-infected patients and 106
      control healthy individuals were enrolled. The level of serum hs-CRP (median
      1.023 mg/L, range 0.03~5.379 mg/L) was significantly lower in all 106 patients
      than that in controls (median 3.147 mg/L, range 0.08~7.36 mg/L, P = 0.012).
      Although hs-CRP did not correlate significantly with NT-proBNP when all patients
      and controls were included (r = 0.169, P = 0.121), simple regression analysis
      demonstrated a statistically significant linear correlation between hs-CRP and NT
      proBNP in HCV-infected patients group (r = 0.392, P = 0.017). Independent
      correlates of hs-CRP levels (R(2) = 0.13) were older age (beta' = 0.031, P =
      0.025) and NT proBNP (beta' = 0.024, P = 0.017). CONCLUSIONS: Although the level
      of serum hs-CRP decreased significantly, there was a significant association
      between hs-CRP and NT-proBNP in HCV-infected patients.

PMID- 22645407
TI  - The deleterious influence of tenofovir-based therapies on the progression of
      atherosclerosis in HIV-infected patients.
AB  - We investigated the potential differential effects of antiretroviral therapies on
      unbalanced chemokine homeostasis and on the progression of atherosclerosis in HIV
      infected patients. A two-year prospective study was performed in 67 consecutive
      HIV-infected patients initiating antiretroviral therapy with abacavir/lamivudine
      or tenofovir/emtricitabine. Circulating levels of inflammatory biomarkers,
      progression of subclinical atherosclerosis and expression levels of selected
      chemokines genes in circulating leukocytes were assessed. Control subjects showed
      significantly lower plasma concentrations of CRP, tPA, IL-6, and MCP-1 than HIV
      infected patients at a baseline. After two years of followup, the observed
      decreases in plasma inflammatory biomarker levels were only significant for MCP
      1, tPA, and IL-6. The decrease in plasma MCP-1 concentration was associated with
      the progression of atherosclerosis, and this effect was negligible only in
      patients receiving TDF-based therapy. Multivariate analysis confirmed that
      treatment with TDF was positively and significantly associated with a higher
      likelihood of subclinical atherosclerosis progression. However, the expression
      levels of selected genes in blood cells only showed associations with the viral
      load and total and HDL-cholesterol levels. Current antiretroviral treatments may
      partially attenuate the influence of HIV infection on certain inflammatory
      pathways, though patients receiving TDF therapy must be carefully monitored with
      respect to the presence and/or progression of atherosclerosis.

PMID- 22645410
TI  - Tetrameranthus (Annonaceae) revisited including a new species.
AB  - The taxonomic revision of the infrequently collected genus Tetrameranthus by
      Westra (1985) is updated. A new species is described from French Guiana and
      Amapa, Brazil, increasing the number of species in this genus to seven.

PMID- 22645409
TI  - Molecular imaging of mesothelioma with (99m)Tc-ECG and (68)Ga-ECG.
AB  - We have developed ethylenedicysteine-glucosamine (ECG) as an alternative to (18)F
      fluoro-2-deoxy-D-glucose ((18)F-FDG) for cancer imaging. ECG localizes in the
      nuclear components of cells via the hexosamine biosynthetic pathway. This study
      was to evaluate the feasibility of imaging mesothelioma with (99m)Tc-ECG and
      (68)Ga-ECG. ECG was synthesized from thiazolidine-4-carboxylic acid and 1,3,4,6
      tetra-O-acetyl-2-amino-D-glucopyranose, followed by reduction in sodium and
      liquid ammonia to yield ECG (52%). ECG was chelated with (99m)Tc/tin (II) and
      (68)Ga/(69)Ga chloride for in vitro and in vivo studies in mesothelioma. The
      highest tumor uptake of (99m)Tc-ECG is 0.47 at 30 min post injection, and
      declined to 0.08 at 240 min post injection. Tumor uptake (%ID/g), tumor/lung,
      tumor/blood, and tumor/muscle count density ratios for (99m)Tc-ECG (30-240 min)
      were 0.47 +/- 0.06 to 0.08 +/- 0.01; 0.71 +/- 0.07 to 0.85 +/- 0.04; 0.47 +/-
      0.03 to 0.51 +/- 0.01, and 3.49 +/- 0.24 to 5.06 +/- 0.25; for (68)Ga-ECG (15-60
      min) were 0.70 +/- 0.06 to 0.92 +/- 0.08; 0.64 +/- 0.05 to 1.15 +/- 0.08; 0.42 +/
      0.03 to 0.67 +/- 0.07, and 3.84 +/- 0.52 to 7.00 +/- 1.42; for (18)F-FDG (30-180
      min) were 1.86 +/- 0.22 to 1.38 +/- 0.35; 3.18 +/- 0.44 to 2.92 +/- 0.34, 4.19 +/
      0.44 to 19.41 +/- 2.05 and 5.75 +/- 2.55 to 3.33 +/- 0.65, respectively. Tumor
      could be clearly visualized with (99m)Tc-ECG and (68)Ga-ECG in mesothelioma
      bearing rats. (99m)Tc-ECG and (68)Ga-ECG showed increased uptake in mesothelioma,
      suggesting they may be useful in diagnosing mesothelioma and also monitoring
      therapeutic response.

PMID- 22645411
TI  - Synopsis of Trichosanthes (Cucurbitaceae) based on recent molecular phylogenetic
      data.
AB  - The snake gourd genus, Trichosanthes, is the largest genus in the Cucurbitaceae
      family, with over 90 species. Recent molecular phylogenetic data have indicated
      that the genus Gymnopetalum is to be merged with Trichosanthes to maintain
      monophyly. A revised infrageneric classification of Trichosanthes including
      Gymnopetalum is proposed with two subgenera, (I) subg. Scotanthus comb. nov. and
      (II) subg. Trichosanthes, eleven sections, (i) sect. Asterospermae, (ii) sect.
      Cucumeroides, (iii) sect. Edulis, (iv) sect. Foliobracteola, (v) sect.
      Gymnopetalum, (vi) sect. Involucraria, (vii) sect. Pseudovariifera sect. nov.,
      (viii) sect. Villosae stat. nov., (ix) sect. Trichosanthes, (x) sect.
      Tripodanthera, and (xi) sect. Truncata. A synopsis of Trichosanthes with the 91
      species recognized here is presented, including four new combinations,
      Trichosanthes orientalis, Trichosanthes tubiflora, Trichosanthes scabra var.
      pectinata, Trichosanthes scabra var. penicaudii, and a clarified nomenclature of
      Trichosanthes costata and Trichosanthes scabra.

PMID- 22645412
TI  - A new species of Miconia (Melastomataceae, Miconieae) from the Ecuador-Peru
      border.
AB  - Miconia machinazana C.Ulloa & D.A. Neill, sp. nov.,a new species of
      Melastomataceae from the Ecuador-Peru border is described and illustrated. It is
      characterized by the narrow, decussate leaves, dense reddish brown indument,
      small flowers in short panicles, pale yellow petals, and anthers opening by two
      large terminal pores.

PMID- 22645413
TI  - A new species of Dorstenia (Moraceae) from southeastern Brazil.
AB  - Dorstenia stellaris is a new species from southeastern Brazil. This species is
      endemic to the region and differs from the others by its star shaped coenanthium
      and cordiform leaves. A description and illustration of this species is presented
      here. Dorstenia stellaris is found in moist and shady places, in small
      populations within the type locality, thus we recommend its inclusion in the
      endangered (EN) status of conservation.

PMID- 22645414
TI  - A new species of Camchaya (Asteraceae, Vernonieae) from Thailand.
AB  - Camchaya thailandica Bunwong, Chantar. & S.C.Keeley, sp. nov. from Phu Phrabat
      Historical Park, Udon Thani, Thailandis described as a new species. Plant of this
      new species are similar to Camchaya gracilis (Gagnep.) Bunwong & H.Rob. but
      differ in having ovate phyllaries without margin spines, 10-ribbed achenes, and
      broadly ovate leaves. This species is a rare endemic known only from the type
      collection and probably confined to open areas of sandstone hills in Udon Thani
      province.

PMID- 22645415
TI  - rAAV Vectors as Safe and Efficient Tools for the Stable Delivery of Genes to
      Primary Human Chondrosarcoma Cells In Vitro and In Situ.
AB  - Treatment of chondrosarcoma remains a major challenge in orthopaedic oncology.
      Gene transfer strategies based on recombinant adenoassociated viral (rAAV)
      vectors may provide powerful tools to develop new, efficient therapeutic options
      against these tumors. In the present study, we tested the hypothesis that rAAV is
      adapted for a stable and safe delivery of foreign sequences in human
      chondrosarcoma tissue by transducing primary human chondrosarcoma cells in vitro
      and in situ with different reporter genes (E. coli lacZ, firefly luc, Discosoma
      sp. RFP). The effects of rAAV administration upon cell survival and metabolic
      activities were also evaluated to monitor possibly detrimental effects of the
      gene transfer method. Remarkably, we provide evidence that efficient and
      prolonged expression of transgene sequences via rAAV can be safely achieved in
      all the systems investigated, demonstrating the potential of the approach of
      direct application of therapeutic gene vectors as a means to treat
      chondrosarcoma.

PMID- 22645416
TI  - Archaeal phospholipid biosynthetic pathway reconstructed in Escherichia coli.
AB  - A part of the biosynthetic pathway of archaeal membrane lipids, comprised of 4
      archaeal enzymes, was reconstructed in the cells of Escherichia coli. The genes
      of the enzymes were cloned from a mesophilic methanogen, Methanosarcina
      acetivorans, and the activity of each enzyme was confirmed using recombinant
      proteins. In vitro radioassay showed that the 4 enzymes are sufficient to
      synthesize an intermediate of archaeal membrane lipid biosynthesis, that is, 2,3
      di-O-geranylgeranyl-sn-glycerol-1-phosphate, from precursors that can be produced
      endogenously in E. coli. Introduction of the 4 genes into E. coli resulted in the
      production of archaeal-type lipids. Detailed liquid chromatography/electron spray
      ionization-mass spectrometry analyses showed that they are metabolites from the
      expected intermediate, that is, 2,3-di-O-geranylgeranyl-sn-glycerol and 2,3-di-O
      geranylgeranyl-sn-glycerol-1-phosphoglycerol. The metabolic processes, that is,
      dephosphorylation and glycerol modification, are likely catalyzed by endogenous
      enzymes of E. coli.

PMID- 22645417
TI  - Understanding autism in schizophrenia.
AB  - Detachment from external reality, distancing from others, closure into a sort of
      virtual hermitage, and prevalence of inner fantasies, are the descriptive aspects
      of autism. However, from an anthropological-phenomenological point of view, in
      schizophrenia, the autistic mode of life can arise from a person's being
      confronted with a pathological crisis in the obviousness of the intersubjective
      world, essentially a crisis in the intersubjective foundation of human presence.
      The "condition of possibility" of the autistic way of being is the deficiency of
      the operation that phenomenology call empathetic-intuitive constitution of the
      Other, an Other which is the naturalness of evidence of being a subject like me.
      The theme of the Other, of intersubjectivity, has become so central in the
      psychopathological analysis of schizophrenic disorders because the modifications
      of interhuman encounter cannot be seen as the secondary consequences of symptoms
      but constitute the fundamental disorder of schizophrenic alienation. Revision of
      the concept of autism from the original definition, centered on the prevalence of
      inner fantasies, leads to the profound change with the vision of autism as "loss"
      and "void." I call attention to possibility of phenomenological research to
      understand autistic world starting from this "void."

PMID- 22645418
TI  - Social competence as a positive youth development construct: a conceptual review.
AB  - Social competence is defined in terms of interpersonal relationships, self and
      group identities, and development of citizenship. While the focus of the author's
      previous research is on relationship and identity, the main focus of this paper
      is on the development of citizenship. A 4-stage developmental model of
      citizenship is proposed. A brief discussion of the educational implication of
      each of the stages is presented. The issues concerning the assessment of social
      competence are clearly delineated, and the discussion serves as a basis for
      future studies. Finally, five current issues concerning the launch of the "Moral
      and National Education (MNE) Subject" in Hong Kong primary and secondary schools
      are discussed.

PMID- 22645419
TI  - The involvement of angiotensin type 1 and type 2 receptors in estrogen-induced
      cell proliferation and vascular endothelial growth factor expression in the rat
      anterior pituitary.
AB  - The aim of our study was to examine the involvement of renin-angiotensin system
      (RAS) in estrogen-induced lactotropes proliferation and vascular endothelial
      growth factor (VEGF) expression in rat pituitary. The study was performed on
      Fisher 344 rats underwent 8-day treatment with diethylstilboestrol (DES). The
      proliferation index (PCNA) and VEGF expression in pituitary sections were
      estimated using immunohistochemical methods. Treatment with DES increased the
      number of PCNA-positive cells, VEGF-positive cells, and VEGF-positive blood
      vessels in pituitary. Stimulatory effect of estrogen on cell proliferation and
      VEGF expression in blood vessels was attenuated by losartan, PD123319, and
      captopril. VEGF immunoreactivity in pituitary cells of DES-treated rats was
      decreased by AT1 antagonist and not changed by AT2 blocker and ACE inhibitor. Our
      findings suggest the involvement of RAS in DES-induced cell proliferation and
      VEGF expression in pituitary. Both the AT1 and AT2 receptors appear to mediate
      the estrogen-dependent mitogenic and proangiogenic effects in rat pituitary.

PMID- 22645420
TI  - Enhanced morbidity of pectoralis major myocutaneous flap used for salvage after
      previously failed oncological treatment and unsuccessful reconstructive head and
      neck surgery.
AB  - INTRODUCTION: The reconstruction of complex cervicofacial defects arising from
      surgical treatment for cancer is a real challenge for head and neck surgeons,
      especially in salvage reconstruction surgery and/or failed previous
      reconstruction. The pectoralis major myocutaneous flap (PMMF) has been widely
      used in these specific situations due to its reliability and low rate of failure
      or complications. OBJECTIVES: Identify factors that determine complications and
      influence the final outcome of the reconstructions with PMMF in salvage cancer
      surgery or in salvage reconstruction. METHODS: A cross-sectional study design was
      used to evaluate a sample including 17 surgical patients treated over a period of
      ten years that met the inclusion criteria. RESULTS: Reconstruction was successful
      in 13 cases (76.5%), with two cases of partial flap loss and no case of total
      loss. Complications occurred in 13 cases (76.5%) and were specifically related to
      the flap in nine instances (52.9%). An association was identified between the
      development of major complications and reconstruction of the hypopharynx (P =
      0.013) as well as in patients submitted to surgery in association with radiation
      therapy as a previous cancer treatment (P = 0.002). The former condition is also
      associated with major reconstruction failure (P = 0.018). An even lower incidence
      of major complications was noted in patients under the age of 53 (P = 0.044).
      CONCLUSION: Older patients, with hypopharyngeal defects and submitted to previous
      surgery plus radiation therapy, presented a higher risk of complications and
      reconstruction failure with PMMF.

PMID- 22645421
TI  - Mid- and long-term results of endovascular treatment in thoracic aorta blunt
      trauma.
AB  - STUDY AIM: Evaluation of results in blunt injury of the thoracic aorta (BAI)
      endovascular treatment. MATERIALS AND METHODS: Sixteen patients were treated for
      BAI. Thirteen patients had associated polytrauma, 4 of these had a serious
      hypotensive status and 4 had an hemothorax. In the remaining 3, two had a post
      traumatic false aneurysm of the isthmus and 1 had a segmental dissection. In
      those 13 patients a periaortic hematoma was associated to hemothorax in 4. All
      patients were submitted to an endovascular treatment, in two cases the subclavian
      artery ostium was intentionally covered. RESULTS: One patient died for
      disseminated intravascular coagulation. No paraplegia was recorded. No ischemic
      complications were observed. A type I endoleak was treated by an adjunctive cuff.
      During the followup (1-9 years) 3 patients were lost. A good patency and no
      endoleaks were observed in all cases. One infolding and 1 migration of the
      endografts were corrected by an adjunctive cuff. CONCLUSION: The medium and long
      term results of the endovascular treatment of BAI are encouraging with a low
      incidence rate of mortality and complications. More suitable endo-suite and
      endografts could be a crucial point for the further improvement of these results.

PMID- 22645422
TI  - Influence of implantable hearing aids and neuroprosthesison music perception.
AB  - The identification and discrimination of timbre are essential features of music
      perception. One dominating parameter within the multidimensional timbre space is
      the spectral shape of complex sounds. As hearing loss interferes with the
      perception and enjoyment of music, we approach the individual timbre
      discrimination skills in individuals with severe to profound hearing loss using a
      cochlear implant (CI) and normal hearing individuals using a bone-anchored
      hearing aid (Baha). With a recent developed behavioral test relying on
      synthetically sounds forming a spectral continuum, the timbre difference was
      changed adaptively to measure the individual just noticeable difference (JND) in
      a forced-choice paradigm. To explore the differences in timbre perception
      abilities caused by the hearing mode, the sound stimuli were varied in their
      fundamental frequency, thus generating different spectra which are not completely
      covered by a CI or Baha system. The resulting JNDs demonstrate differences in
      timbre perception between normal hearing individuals, Baha users, and CI users.
      Beside the physiological reasons, also technical limitations appear as the main
      contributing factors.

PMID- 22645423
TI  - Self-efficacy as a positive youth development construct: a conceptual review.
AB  - Self-efficacy denotes people's beliefs about their ability to perform in
      different situations. It functions as a multilevel and multifaceted set of
      beliefs that influence how people feel, think, motivate themselves, and behave
      during various tasks. Self-efficacy beliefs are informed by enactive attainment,
      vicarious experience, imaginal experiences, and social persuasion as well as
      physical and emotional states. These beliefs are mediated by cognitive,
      motivational, affective, and selection processes to generate actual performance.
      Self-efficacy development is closely intertwined with a person's experiences,
      competencies, and developmental tasks in different domains at different stages in
      life. This paper reviews the literature to outline the definition and theoretical
      conceptualizations of the construct originally devised by Bandura that have
      flourished since the 1990s. Drawing from the studies of the construct to assess
      self-efficacy, and to inform positive youth development, the paper will present
      the determinants of the development of self-efficacy beliefs and identify the
      connection between self-efficacy and adolescent developmental outcomes. The paper
      will conclude with strategies to enhance youth self-efficacy and proposals for
      future research directions.

PMID- 22645425
TI  - Leukotrienes as modifiers of preclinical atherosclerosis?
AB  - Preclinical atherosclerosis represents a crucial period associated with several
      pathophysiological reactions in the vascular wall. Failure to diagnose
      preclinical atherosclerosis at this stage misses a major opportunity to prevent
      the long-term consequences of this disease. Surrogate biological and structural
      vascular markers are available to determine the presence and the extension of
      preclinical vascular injury in the general population. Examples of surrogate
      markers are carotid intima media thickness and biomarkers including high
      sensitivity C-reactive protein, cell adhesion molecules and matrix
      metalloproteinases, and leukotrienes. Recently, leukotrienes have been implicated
      as mediators, biomarkers, and possible therapeutic targets in the context of
      subclinical atherosclerosis. The aim of this short paper is to focus on the
      relation between preclinical atherosclerosis and leukotrienes, with particular
      attention to the recent development on the use of leukotriene modifiers in the
      treatment of atherosclerosis.

PMID- 22645424
TI  - Hypertonic saline in treatment of pulmonary disease in cystic fibrosis.
AB  - The pathogenesis of lung disease in cystic fibrosis is characterised by decreased
      airway surface liquid volume and subsequent failure of normal mucociliary
      clearance. Mucus within the cystic fibrosis airways is enriched in negatively
      charged matrices composed of DNA released from colonizing bacteria or
      inflammatory cells, as well as F-actin and elevated concentrations of anionic
      glycosaminoglycans. Therapies acting against airway mucus in cystic fibrosis
      include aerosolized hypertonic saline. It has been shown that hypertonic saline
      possesses mucolytic properties and aids mucociliary clearance by restoring the
      liquid layer lining the airways. However, recent clinical and bench-top studies
      are beginning to broaden our view on the beneficial effects of hypertonic saline,
      which now extend to include anti-infective as well as anti-inflammatory
      properties. This review aims to discuss the described therapeutic benefits of
      hypertonic saline and specifically to identify novel models of hypertonic saline
      action independent of airway hydration.

PMID- 22645427
TI  - Changes of peel essential oil composition of four Tunisian citrus during fruit
      maturation.
AB  - The present work investigates the effect of ripening stage on the chemical
      composition of essential oil extracted from peel of four citrus: bitter orange
      (Citrus aurantium), lemon (Citrus limon), orange maltaise (Citrus sinensis), and
      mandarin (Citrus reticulate) and on their antibacterial activity. Essential oils
      yields varied during ripening from 0.46 to 2.70%, where mandarin was found to be
      the richest. Forty volatile compounds were identified. Limonene (67.90-90.95%)
      and 1,8-cineole (tr-14.72%) were the most represented compounds in bitter orange
      oil while limonene (37.63-69.71%), beta-pinene (0.63-31.49%), gamma-terpinene
      (0.04-9.96%), and p-cymene (0.23-9.84%) were the highest ones in lemon. In the
      case of mandarin, the predominant compounds were limonene (51.81-69.00%), 1,8
      cineole (0.01-26.43%), and gamma-terpinene (2.53-14.06%). However, results showed
      that orange peel oil was dominated mainly by limonene (81.52-86.43%) during
      ripening. The results showed that ripening stage influenced significantly the
      antibacterial activity of the oils against Staphylococcus aureus, Escherichia
      coli, and Pseudomonas aeruginosa. This knowledge could help establish the optimum
      harvest date ensuring the maximum essential oil, limonene, as well as
      antibacterial compounds yields of citrus.

PMID- 22645426
TI  - CD40 Gene polymorphisms associated with susceptibility and coronary artery
      lesions of Kawasaki disease in the Taiwanese population.
AB  - BACKGROUND: Kawasaki disease (KD) is characterized by systemic vasculitis of
      unknown etiology. Our previous studies showed expression of CD40 ligand on CD4+ T
      cells correlated to the coronary artery lesion (CAL) and disease progress in KD.
      Other studies from Japan suggested the role of CD40L in the pathogenesis of CAL,
      and this might help explain the excessive number of males affected with KD but
      cannot be reproduced by Taiwanese population. This study was conducted to
      investigate the CD40 polymorphism in KD and CAL formation. METHODS: A total of
      950 subjects (381 KD patients and 569 controls) were investigated to identify 2
      tagging single-nucleotide polymorphisms (tSNPs) of CD40 (rs4810485 and rs1535045)
      by using the TaqMan allelic discrimination assay. RESULTS: A significant
      association was noted with regards to CD40 tSNPs (rs1535045) between controls and
      KD patients (P = 0.0405, dominant model). In KD patients, polymorphisms of CD40
      (rs4810485) showed significant association with CAL formation (P = 0.0436,
      recessive model). Haplotype analysis did not yield more significant results
      between polymorphisms of CD40 and susceptibility/disease activity of KD.
      CONCLUSIONS: This study showed for the first time that polymorphisms of CD40 are
      associated with susceptibility to KD and CAL formation, in the Taiwanese
      population.

PMID- 22645428
TI  - Engineering the production of major catechins by Escherichia coli carrying
      metabolite genes of Camellia sinensis.
AB  - A mimicked biosynthetic pathway of catechin metabolite genes from C. sinensis,
      consisting of flavanone 3 hydroxylase (F3H), dihydroflavonol reductase (DFR), and
      leucoanthocyanidin reductase (LCR), was designed and arranged in two sets of
      constructs: (a) single promoter in front of F3H and ribosome-binding sequences
      both in front of DFR and LCR; (b) three different promoters with each in the
      front of the three genes and ribosome-binding sequences at appropriate positions.
      Recombinant E. coli BL (DE3) harbouring the constructs were cultivated for 65 h
      at 26  degrees C in M9 medium consisting of 40 g/L glucose, 1 mM IPTG, and 3 mM
      eriodictyol. Compounds produced were extracted in ethyl acetate in alkaline
      conditions after 1 h at room temperature and identified by HPLC. Two of the four
      major catechins, namely, (-)-epicatechin (0.01) and (-)-epicatechin gallate (0.36
      mg/L), and two other types ((+)-catechin hydrate (0.13 mg/L) and (-)-catechin
      gallate (0.04 mg/L)) were successfully produced.

PMID- 22645429
TI  - The waterlogging tolerance of wheat varieties in western of Turkey.
AB  - This research was conducted to determine the wheat varieties against waterlogging
      which was clearly increased in recent years. For this purpose, this study was
      performed at Field Crops and Soil Science Department of Agricultural Faculty of
      Adnan Menderes University during wheat growth stages of 2007-2008. The
      experimental design was randomized complete block design with split split plot
      arrangements. The main plots were temperature applications (heat and normal), the
      growth periods (Zadoks scale; GS14, GS32, GS14 + GS32, and control) were split
      plots and varieties were split-split plots. The eight different wheat varieties
      were evaluated in the pots. The waterlogging was performed during GS14, GS32 and
      GS14 + GS32. In a pot experiment, plants were subjected to waterlogging to the
      soil surface for 10 days. All applications and varieties decreased the single
      plant yield. The waterlogging caused a yield loss compared with wheat grown on
      well-drained soil. In this study, the crop loss due to waterlogging is highly
      temperature dependent. The severity of the effects of the waterlogging depends on
      the growth stage of the plot. When all applications were compared with control by
      means of yield performance, Sagittario and Basribey varieties were less affected
      than the others.

PMID- 22645430
TI  - LOX Gene transcript accumulation in olive (Olea europaea L.) fruits at different
      stages of maturation: relationship between volatile compounds, environmental
      factors, and technological treatments for oil extraction.
AB  - The quality of olive oil is influenced by genetic and environmental factors and
      by the maturation state of drupes, but it is equally affected by technological
      treatments of the process. This work investigates the possible correlation
      between olive LOX gene transcript accumulation, evaluated in fruits collected at
      different stages of maturation, and chemical biomarkers of its activity. During
      olive fruit ripening, the same genotype harvested from two different farms shows
      a positive linear trend between LOX relative transcript accumulation and the
      content of volatile compounds present in the olive oil aroma. Interestingly, a
      negative linear trend was observed between LOX relative transcript accumulation
      and the content of volatile compounds present in the olive pastes obtained from
      olive fruits with and without malaxation. The changes in the olive LOX transcript
      accumulation reveal its environmental regulation and suggest differential
      physiological functions for the LOXs.

PMID- 22645431
TI  - Expressions of MMPs and TIMP-1 in gastric ulcers may differentiate H. pylori
      infected from NSAID-related ulcers.
AB  - BACKGROUND: Two major causes of gastric ulcers are Helicobacter pylori (H.
      pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) use. AIMS: This
      study aimed to determine if there were different expressions of matrix
      metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinase-1
      (TIMP-1) between H. pylori-infected and NSAID-related ulcers. METHODS: The 126
      gastric ulcer patients (H. pylori infected n = 46; NSAID related n = 30; combined
      with two factors n = 50) provided ulcer and nonulcer tissues for assessment of
      MMP-3, -7, and -9 and TIMP-1 expression by immunohistochemical staining. RESULTS:
      Gastric ulcer tissues had significantly higher MMP-3, -7, and -9 and TIMP-1
      expressions than nonulcer tissues (P < 0.05). H. pylori-infected gastric ulcers
      had even higher MMP-7, MMP-9, and TIMP-1 expressions in epithelial cells than
      NSAID-related gastric ulcers (P < 0.05). In patients with the two combined
      factors, gastric ulcers expressed similar proportions of antral ulcers and MMP-7
      and MMP-9 intensities to NSAID-related gastric ulcers, but lower MMP-9 and TIMP-1
      than H. pylori-infected gastric ulcers (P < 0.05). CONCLUSIONS: H. pylori
      infected gastric ulcers express higher MMP-7, MMP-9, and TIMP-1 than NSAID
      related ulcers. In patients with the two combined factors, ulcer location and MMP
      7 and MMP-9 intensities are similar to NSAID use.

PMID- 22645432
TI  - An evaluation of leaf biomass : length ratio as a tool for nondestructive
      assessment in eelgrass (Zostera marina L.).
AB  - The characterization of biomass and its dynamics provides valuable information
      for the assessment of natural and transplanted eelgrass populations. The need for
      simple, nondestructive assessments has led to the use of the leaf biomass-to
      length ratio for converting leaf-length measurements, which can be easily
      obtained, to leaf growth rates through the plastochrone method. Using data on
      leaf biomass and length collected in three natural eelgrass populations and a
      mesocosm, we evaluated the suitability of a leaf weight-to-length ratio for
      nondestructive assessments. For the data sets considered, the isometric scaling
      that sustains the weight-to-length proxy always produced inconsistent fittings,
      and for leaf-lengths greater than a threshold value, the conversion of leaf
      length to biomass generated biased estimations. In contrast, an allometric
      scaling of leaf biomass and length was highly consistent in all the cases
      considered. And these nondestructive assessments generated reliable levels of
      reproducibility in leaf biomass for all the ranges of variability in leaf
      lengths. We argue that the use of allometric scaling for the representation of
      leaf biomass in terms of length provides a more reliable approach for estimating
      eelgrass biomass.

PMID- 22645433
TI  - Effects of zearalenone on IL-2, IL-6, and IFN-gamma mRNA levels in the splenic
      lymphocytes of chickens.
AB  - Zearalenone (ZEN) is an estrogenic mycotoxin produced by several Fusarium
      species, which can contaminate food and feed. These compounds elicit a wide
      spectrum of toxic effects, including the capacity to alter normal immune
      function. In this study, the in vitro effects of the treatment of ConA-stimulated
      splenic lymphocytes with ZEN (0-25 MUg/mL) were examined. ZEN modulates the
      expression of IL-2, IL-6, and IFN-gamma. The IL-2 levels were up to fourfold
      higher (P < 0.05) compared with the levels in the control at toxin concentrations
      of 25 MUg/mL after 48 h of treatment. The IL-6 levels were critically suppressed
      at this concentration; these changes were very statistically significant (P <
      0.05). At lower ZEN concentrations (0.1, 0.4 and 1.6 MUg/mL), the IFN-gamma
      levels changed slightly; however at 6.25 and 25 MUg/mL, the IFN-gamma results
      reached statistical significance compared with the control levels (P < 0.05).
      These data suggest that ZEN has potent effects on the expression of chicken
      splenic lymphocytes cytokines at the mRNA level.

PMID- 22645434
TI  - Behavioral competence as a positive youth development construct: a conceptual
      review.
AB  - Behavioral competence is delineated in terms of four parameters: (a) Moral and
      Social Knowledge, (b) Social Skills, (c) Positive Characters and Positive
      Attributes, and (d) Behavioral Decision Process and Action Taking. Since Ma's
      other papers in this special issue have already discussed the moral and social
      knowledge as well as the social skills associated in detail, this paper focuses
      on the last two parameters. It is hypothesized that the following twelve positive
      characters are highly related to behavioral competence: humanity, intelligence,
      courage, conscience, autonomy, respect, responsibility, naturalness, loyalty,
      humility, assertiveness, and perseverance. Large-scale empirical future studies
      should be conducted to substantiate the predictive validity of the complete set
      of these positive characters. The whole judgment and behavioral decision process
      is constructed based on the information processing approach. The direction of
      future studies should focus more on the complex input, central control, and
      output subprocesses and the interactions among these sub-processes. The
      understanding of the formation of behavior is crucial to whole-person education
      and positive youth development.

PMID- 22645435
TI  - INVO procedure: minimally invasive IVF as an alternative treatment option for
      infertile couples.
AB  - Intravaginal culture (IVC), also called INVO (intravaginal culture of oocytes),
      is an assisted reproduction procedure where oocyte fertilization and early embryo
      development are carried out within a gas permeable air-free plastic device,
      placed into the maternal vaginal cavity for incubation. In the present study we
      assessed the outcome of the INVO procedure, using the recently designed INVOcell
      device, in combination with a mild ovarian stimulation protocol. A total of 125
      cycles were performed. On average 6.5 oocytes per cycle were retrieved, and a
      mean of 4.2 were placed per INVOcell device. The cleavage rate obtained after the
      INVO culture was 63%. The procedure yielded 40%, 31.2%, and 24% of clinical
      pregnancy, live birth, and single live birth rates per cycle, respectively. Our
      results suggest that the INVO procedure is an effective alternative treatment
      option in assisted reproduction that shows comparable results to those reported
      for existing IVF techniques.

PMID- 22645436
TI  - Central precocious puberty: treatment with triptorelin 11.25 mg.
AB  - BACKGROUND: Few data are available on quarterly 11.25 mg GnRH analog treatment in
      central precocious puberty (CPP). AIM: To assess the efficacy of triptorelin
      11.25 mg in children with CPP. PATIENTS: 17 patients (16 females) with CPP (7.9
      +/- 0.9 years) were treated with triptorelin 11.25 mg/90 days. METHODS:
      Gonadotropins, basal-, and GnRH-stimulated peak, gonadal steroids, and pubertal
      signs were assessed at preinclusion and at inclusion visit, 3 months, 6 months,
      and 12 months of treatment. Results. At 3, 6, and 12 months, all patients had
      suppressed LH peak (<3 IU/L after GnRH stimulation), as well as prepubertal
      oestradiol levels. Mean LH peak values after GnRH test significantly decreased
      from 25.7 +/- 16.5 IU/L at baseline to 0.9 +/- 0.5 IU/L at M3 (P < 0.0001); they
      did not significantly changed at M6 and M12. CONCLUSIONS: Triptorelin 11.25 mg/90
      days efficiently suppressed the pituitary-gonadal axis in children with CPP from
      first administration.

PMID- 22645437
TI  - Source apportionment of PM10 by positive matrix factorization in urban area of
      Mumbai, India.
AB  - Particulate Matter (PM(10)) has been one of the main air pollutants exceeding the
      ambient standards in most of the major cities in India. During last few years,
      receptor models such as Chemical Mass Balance, Positive Matrix Factorization
      (PMF), PCA-APCS and UNMIX have been used to provide solutions to the source
      identification and contributions which are accepted for developing effective and
      efficient air quality management plans. Each site poses different complexities
      while resolving PM(10) contributions. This paper reports the variability of four
      sites within Mumbai city using PMF. Industrial area of Mahul showed sources such
      as residual oil combustion and paved road dust (27%), traffic (20%), coal fired
      boiler (17%), nitrate (15%). Residential area of Khar showed sources such as
      residual oil combustion and construction (25%), motor vehicles (23%), marine
      aerosol and nitrate (19%), paved road dust (18%) compared to construction and
      natural dust (27%), motor vehicles and smelting work (25%), nitrate (16%) and
      biomass burning and paved road dust (15%) in Dharavi, a low income slum
      residential area. The major contributors of PM(10) at Colaba were marine aerosol,
      wood burning and ammonium sulphate (24%), motor vehicles and smelting work (22%),
      Natural soil (19%), nitrate and oil burning (18%).

PMID- 22645438
TI  - Robust optimization of alginate-Carbopol 940 bead formulations.
AB  - Formulation process is a very complex activity which sometimes implicates taking
      decisions about parameters or variables to obtain the best results in a high
      variability or uncertainty context. Therefore, robust optimization tools can be
      very useful for obtaining high quality formulations. This paper proposes the
      optimization of different responses through the robust Taguchi method. Each
      response was evaluated like a noise variable, allowing the application of Taguchi
      techniques to obtain a response under the point of view of the signal to noise
      ratio. A L(18) Taguchi orthogonal array design was employed to investigate the
      effect of eight independent variables involved in the formulation of alginate
      Carbopol beads. Responses evaluated were related to drug release profile from
      beads (t(50%) and AUC), swelling performance, encapsulation efficiency, shape and
      size parameters. Confirmation tests to verify the prediction model were carried
      out and the obtained results were very similar to those predicted in every
      profile. Results reveal that the robust optimization is a very useful approach
      that allows greater precision and accuracy to the desired value.

PMID- 22645439
TI  - Simultaneous determination of parathion, malathion, diazinon, and pirimiphos
      methyl in dried medicinal plants using solid-phase microextraction fibre coated
      with single-walled carbon nanotubes.
AB  - A reliable and sensitive headspace solid-phase microextraction gas chromatography
      mass spectrometry method for simultaneous determination of different
      organophosphorus pesticides in dried medicinal plant samples is described. The
      analytes were extracted by single-walled carbon nanotubes as a new solid-phase
      microextraction adsorbent. The developed method showed good performance. For
      diazinon and pirimiphos methyl calibration, curves were linear (r(2) >= 0.993)
      over the concentration ranges from 1.5 to 300 ng g(-1), and the limit of
      detection at signal-to-noise ratio of 3 was 0.3 ng g(-1). For parathion and
      malathion, the linear range and limit of detection were 2.5-300 (r(2) >= 0.991)
      and 0.5 ng g(-1), respectively. In addition, a comparative study between the
      single-walled carbon nanotubes and a commercial polydimethylsiloxane fibre for
      the determination of target analytes was carried out. Single-walled carbon
      nanotubes fibre showed higher extraction capacity, better thermal stability (over
      350  degrees C), and longer lifespan (over 250 times) than the commercial
      polydimethylsiloxane fibre. The developed method was successfully applied to
      determine target organophosphorus pesticides in real samples.

PMID- 22645440
TI  - Effects of glucomannan on the sacculus rotundus and peripheral blood lymphocytes
      in New Zealand rabbits during aflatoxicosis.
AB  - This study was aimed to determine the effects of the glucomannan added to
      aflatoxin- (AF-) contaminated diet on the sacculus rotundus and peripheral blood
      lymphocytes of New Zealand rabbits by histological and enzyme histochemical
      methods. Twenty-four adult rabbits of both sexes were divided into four equal
      groups, namely, as control, glucomannan 0.2 g/day, AF 125 MUg/kg/day, and
      glucomannan combined with AF. The animals in all groups were treated for 12 weeks
      by the above-mentioned diet. When compared to control, AF-treatment caused
      significant decrease in alpha-naphthyl acetate esterase- (ANAE-) positive
      peripheral blood lymphocyte (PBL) percentages. The addition of the glucomannan to
      AFcontaining diet recovered the adverse effects of AF on sacculus rotundus and
      increased the ANAE-positive PBL counts. These results suggested that glucomannan
      was effective against the negative effects of AF in rabbits.

PMID- 22645441
TI  - Prospective study of antibiotic prophylaxis for prostate biopsy involving >1100
      men.
AB  - We aimed to compare infection rates for two 3-day antibiotic prophylaxis regimens
      for transrectal ultrasound-guided prostate biopsy (TRUSgbp) and demonstrate local
      microbiological trends. In 2008, 558 men and, in 2009, 625 men had TRUSgpb.
      Regimen 1 (2008) comprised 400 mg Ofloxacin immediately before biopsy and 200 mg
      12-hourly for 3 days. Regimen 2 (2009) comprised Ofloxacin 200 mg 12-hourly for 3
      days commencing 24 hours before biopsy. 20/558 (3.6%) men had febrile episodes
      with regimen 1 and 10/625 (1.6%) men with regimen 2 (P = 0.03). E. coli was the
      most frequently isolated organism. Overall, 7/13 (54%) of positive urine cultures
      were quinolone resistant and (5/13) 40% were multidrug resistant. Overall, 5/9
      (56%) patients with septicaemia were quinolone resistant. All patients were
      sensitive to Meropenem. There was 1 (0.2%) death with regimen 1. Commencing
      Ofloxacin 24 hours before TRUSgpb reduced the incidence of febrile episodes
      significantly. We observed the emergence of quinolone and multidrug-resistant E.
      coli. Meropenem should be considered for unresolving sepsis.

PMID- 22645442
TI  - Novel ecdysteroids from Serratula wolffii.
AB  - Two new and one known ecdysteroids were identified in the methanolic extract of
      the roots of Serratula wolffii. The new compounds isolated were ponasterone A-22
      apioside (1) and 3-epi-shidasterone (3), together with the known 3-epi-22-deoxy
      20-hydroxyecdysone (2). The structures of compounds 1-3 were determined by
      extensive spectroscopic techniques, including one- and two-dimensional NMR
      methods.

PMID- 22645443
TI  - Distribution of mercury in rainbow trout tissues at embryo-larval and juvenile
      stages.
AB  - The aims of the study were to determine total mercury concentrations in "rainbow
      trout Oncorhynchus mykiss (Walbaum)" at their embryo-larval and juvenile stages
      and to assess mercury concentration dynamics in individual tissues. Samples of
      rainbow trout were collected at two-month intervals over a period of 18 months
      (one stock production cycle) at the Velka Losenice trout farm. Feedstuff samples
      were collected at the same time and analyzed for mercury concentrations. Tissue
      mercury concentrations were determined in muscle, liver, and kidneys. Analyses
      were performed using the AMA 254 atomic absorption spectrophotometer. The lowest
      mercury concentration was found in 14-day-old embryos (hard roe), and the highest
      concentrations in muscle tissue, liver, and kidneys at the end of monitoring,
      that is, in rainbow trout aged 18 months. The amount of mercury in feedstuffs
      showed an increasing trend and ranged between 0.0126 and 0.0859 mg kg(-1). A
      significant effect (P < 0.001) of mercury intake on mercury concentrations in
      muscle tissue, liver, and kidneys was demonstrated. Muscle mercury concentrations
      in 18-month-old market-ready rainbow trout of 0.128 +/- 0.048 mg kg(-1) met the
      criteria for fish meat hygiene.

PMID- 22645444
TI  - Leech-like parasites (Clitellata, Acanthobdellida) infecting native and endemic
      eastern Siberian salmon fishes.
AB  - Salmonoid fish bdellosis is caused by leech-like ectoparasites in the monogenetic
      order Acanthobdellida. Although Acanthobdella species have been known to infect
      several threatened species in Eurasia, little is known about their ecology and
      epidemiology. In this paper, we report on the mass affection (up to 70.7%) of
      fish in lower course of the Chechuj River, a right tributary of the Lena and
      provide information on finding Acanthobdella peledina on two of six salmonoid
      fish species inhabiting there: lenok and grayling. New and more specific data on
      morphological peculiarities and feeding strategy were obtained. The ratio of body
      length to width in studied acanthobdellid collection is significantly less than
      one provided for the A. livanowi and the rest A. peledina from other water
      systems of Eurasia. Biology and lifestyle of the parasite population are revealed
      for the first time.

PMID- 22645445
TI  - Molecular cloning of phd1 and comparative analysis of phd1, 2, and 3 expression
      in Xenopus laevis.
AB  - Intensive gene targeting studies in mice have revealed that prolyl hydroxylase
      domain proteins (PHDs) play important roles in murine embryonic development;
      however, the expression patterns and function of these genes during embryogenesis
      of other vertebrates remain largely unknown. Here we report the molecular cloning
      of phd1 and systematic analysis of phd1, phd2, and phd3 expression in embryos as
      well as adult tissues of Xenopus laevis. All three phds are maternally provided
      during Xenopus early development. The spatial expression patterns of phds genes
      in Xenopus embryos appear to define a distinct synexpression group. Frog phd2 and
      phd3 showed complementary expression in adult tissues with phd2 transcription
      levels being high in the eye, brain, and intestine, but low in the liver,
      pancreas, and kidney. On the contrary, expression levels of phd3 are high in the
      liver, pancreas, and kidney, but low in the eye, brain, and intestine. All three
      phds are highly expressed in testes, ovary, gall bladder, and spleen. Among three
      phds, phd3 showed strongest expression in heart.

PMID- 22645446
TI  - Isolation, characterization, and identification of biological control agent for
      potato soft rot in Bangladesh.
AB  - A total of 91 isolates of probable antagonistic bacteria of potato soft rot
      bacterium Erwinia carotovora subsp. carotovora (Ecc) were extracted from
      rhizospheres and endophytes of various crop plants, different soil varieties, and
      atmospheres in the potato farming areas of Bangladesh. Antibacterial activity of
      the isolated probable antagonistic bacteria was tested in vitro against the
      previously identified most common and most virulent soft rot causing bacterial
      strain Ecc P-138. Only two isolates E-45 and E-65 significantly inhibited the in
      vitro growth of Ecc P-138. Physiological, biochemical, and carbon source
      utilization tests identified isolate E-65 as a member of the genus Bacillus and
      the isolate E-45 as Lactobacillus sp. The stronger antagonistic activity against
      Ecc P-138 was found in E-65 in vitro screening and storage potatoes. E-65 reduced
      the soft rot infection to 22-week storage potatoes of different varieties by 32.5
      62.5% in model experiment, demonstrating its strong potential to be used as an
      effective biological control agent for the major pectolytic bacteria Ecc. The
      highest (62.5%) antagonistic effect of E-65 was observed in the Granola and the
      lowest (32.7%) of that was found in the Cardinal varieties of the Bangladeshi
      potatoes. The findings suggest that isolate E-65 could be exploited as a
      biocontrol agent for potato tubers.

PMID- 22645447
TI  - Phosphodiesterase inhibitors suppress Lactobacillus casei cell-wall-induced NF
      kappaB and MAPK activations and cell proliferation through protein kinase A--or
      exchange protein activated by cAMP-dependent signal pathway.
AB  - Specific strains of Lactobacillus have been found to be beneficial in treating
      some types of diarrhea and vaginosis. However, a high mortality rate results from
      underlying immunosuppressive conditions in patients with Lactobacillus casei
      bacteremia. Cyclic AMP (cAMP) is a small second messenger molecule that mediates
      signal transduction. The onset and progression of inflammatory responses are
      sensitive to changes in steady-state cAMP levels. L. casei cell wall extract
      (LCWE) develops arteritis in mice through Toll-like receptor-2 signaling. The
      purpose of this study was to investigate whether intracellular cAMP affects LCWE
      induced pathological signaling. LCWE was shown to induce phosphorylation of the
      nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK)
      signaling pathways and cell proliferation in mice fibroblast cells. Theophylline
      and phosphodiesterase inhibitor increased intracellular cAMP and inhibited LCWE
      induced cell proliferation as well as phosphorylation of NF-kappaB and MAPK.
      Protein kinase A inhibitor H89 prevented cAMP-induced MAPK inhibition, but not
      cAMP-induced NF-kappaB inhibition. An exchange protein activated by cAMP (Epac)
      agonist inhibited NF-kappaB activation but not MAPK activation. These results
      indicate that an increase in intracellular cAMP prevents LCWE induction of
      pathological signaling pathways dependent on PKA and Epac signaling.

PMID- 22645448
TI  - Magnetic resonance spectroscopy of the breast at 3T: pre- and post-contrast
      evaluation for breast lesion characterization.
AB  - PURPOSE: To determine whether in vivo proton magnetic resonance spectroscopy at
      3T can provide accurate breast lesion characterization, and to determine the
      effect of gadolinium on the resonance of tCho. METHODS: Twenty-four positive
      mammogram patients were examined on a 3T MR scanner. 1H-MRS was performed before
      and after gadolinium administration. tCho peak was qualitatively evaluated before
      and after contrast injection. RESULTS: Fourteen out of 27 lesions proved to be
      malignant after histopathological diagnosis. Using 1H-MRS, before contrast
      injection, 6/14 confirmed malignancies and 11/13 benign lesions were correctly
      classified; while, after contrast injection, 11/14 confirmed malignancies and
      12/13 benign processes were correctly classified. Post gadolinium 1H-MRS proved
      useful in picking up tCho signal, improving the overall accuracy, sensitivity,
      and specificity by 35%, 83%, and 9%, respectively. CONCLUSION: 1H-MRS overall
      accuracy, sensitivity, and specificity in detecting breast lesion's malignancy
      were increased after gadolinium administration. It is prudent to perform 1H-MRS
      before contrast injection in large breast lesions to avoid choline
      underestimation. In cases of small or non-mass lesions, it is recommended to
      perform 1H-MRS after contrast injection for better voxel prescription to enable a
      reliable preoperative diagnosis.

PMID- 22645449
TI  - The specific characteristics in children with obstructive sleep apnea and cor
      pulmonale.
AB  - BACKGROUND: The prevalence of obstructive sleep apnea (OSA) in the pediatric
      population is currently estimated at 1-2% of all children. The purpose of this
      study was to investigate the clinical and hemodynamic characteristics in
      pediatric patients with cor pulmonale and OSA. METHODS: Thirty children with the
      diagnosis of OSA were included. These patients consisted of 26 male and 4 female
      children with a mean age of 7 +/- 4 years old. Five of those children were found
      to be associated with cor pulmonale, and 25 had OSA but without cor pulmonale.
      RESULTS: The arousal index was much higher in children with OSA and cor
      pulmonale. The children with OSA and cor pulmonale had much lower mean and
      minimal oxygen saturation and a higher incidence of bradycardia events. All 5
      patients with OSA and cor pulmonale underwent an adenotonsillectomy, and the
      pulmonary arterial pressure dropped significantly after the surgery. CONCLUSION:
      This study demonstrated that the OSA pediatric patients with cor pulmonale had
      the different clinical manifestations and hemodynamic characteristics from those
      without cor pulmonale. The adenotonsillectomy had excellent results in both the
      OSA pediatric patients with and without cor pulmonale.

PMID- 22645450
TI  - GP's adherence to guidelines for cardiovascular disease among elderly: a quality
      development study.
AB  - BACKGROUND: Evidence-based guidelines should in most cases be followed also in
      the treatment of elderly. Older people are often suboptimally treated with the
      recommended drugs. OBJECTIVES: To describe how well general practitioners adhere
      to current guidelines in the treatment of elderly with cardiovascular disease and
      evaluate local education as a tool for improvement. METHOD: Data was collected
      from the medical records of patients aged >= 65, who visited a primary health
      care center in Sweden 2006 and had one or more of the following diagnoses:
      hypertension, ischemic heart disease, heart failure, chronic atrial fibrillation,
      or prior stroke. Local education was organized and included feed-back to the
      patient's doctor and discussion about regional guidelines. Repeated measurements
      were performed in 2008. RESULTS AND CONCLUSION: The adherence to guidelines was
      low. Approximately one-third of the patients with hypertension reached target
      blood pressure, stroke patients more often. More patients with heart failure were
      treated with angiotensin converting enzyme inhibitor than in other European
      countries, but still only 60%. Half of the patients with chronic atrial
      fibrillation were treated with Warfarin, although more than two-thirds had a
      CHADS(2) score indicating the need. Educational efforts appeared to increase the
      adherence and hence should be encouraged.

PMID- 22645451
TI  - Improving the s-shape solar radiation estimation method for supporting crop
      models.
AB  - In line with the critical comments formulated in relation to the S-shape global
      solar radiation estimation method, the original formula was improved via a 5-step
      procedure. The improved method was compared to four-reference methods on a large
      North-American database. According to the investigated error indicators, the
      final 7-parameter S-shape method has the same or even better estimation
      efficiency than the original formula. The improved formula is able to provide
      radiation estimates with a particularly low error pattern index (PI(doy)) which
      is especially important concerning the usability of the estimated radiation
      values in crop models. Using site-specific calibration, the radiation estimates
      of the improved S-shape method caused an average of 2.72 +/- 1.02 (alpha = 0.05)
      relative error in the calculated biomass. Using only readily available site
      specific metadata the radiation estimates caused less than 5% relative error in
      the crop model calculations when they were used for locations in the middle,
      plain territories of the USA.

PMID- 22645452
TI  - Experimental hyperthyroidism decreases gene expression and serum levels of
      adipokines in obesity.
AB  - AIMS: To analyze the influence of hyperthyroidism on the gene expression and
      serum concentration of leptin, resistin, and adiponectin in obese animals. MAIN
      METHODS: Male Wistar rats were randomly divided into two groups: control (C)-fed
      with commercial chow ad libitum-and obese (OB)-fed with a hypercaloric diet.
      After group characterization, the OB rats continued receiving a hypercaloric diet
      and were randomized into two groups: obese animals (OB) and obese with 25 MUg
      triiodothyronine (T(3))/100 BW (OT). The T(3) dose was administered every day for
      the last 2 weeks of the study. After 30 weeks the animals were euthanized.
      Samples of blood and adipose tissue were collected for biochemical and hormonal
      analyses as well as gene expression of leptin, resistin, and adiponectin.
      RESULTS: T(3) treatment was effective, increasing fT(3) levels and decreasing
      fT(4) and TSH serum concentration. Administration of T(3) promotes weight loss,
      decreases all fat deposits, and diminishes serum levels of leptin, resistin, and
      adiponectin by reducing their gene expression. CONCLUSIONS: Our results suggest
      that T(3) modulate serum and gene expression levels of leptin, resistin, and
      adiponectin in experimental model of obesity, providing new insights regarding
      the relationship between T(3) and adipokines in obesity.

PMID- 22645453
TI  - The relationship between coenzyme Q10, oxidative stress, and antioxidant enzymes
      activities and coronary artery disease.
AB  - A higher oxidative stress may contribute to the pathogenesis of coronary artery
      disease (CAD). The purpose of this study was to investigate the relationship
      between coenzyme Q10 concentration and lipid peroxidation, antioxidant enzymes
      activities and the risk of CAD. Patients who were identified by cardiac
      catheterization as having at least 50% stenosis of one major coronary artery were
      assigned to the case group (n = 51). The control group (n = 102) comprised
      healthy individuals with normal blood biochemical values. The plasma coenzyme
      Q10, malondialdehyde (MDA) and antioxidant enzymes activities (catalase (CAT),
      superoxide dismutase (SOD), glutathione peroxidase (GPx)) were measured. Subjects
      with CAD had significant lower plasma coenzyme Q10, CAT and GPx activities and
      higher MDA and SOD levels compared to those of the control group. The plasma
      coenzyme Q10 was positively correlated with CAT and GPx activities and negatively
      correlated with MDA and SOD. However, the correlations were not significant after
      adjusting for the potential confounders of CAD with the exception of SOD. A
      higher level of plasma coenzyme Q10 (>= 0.52 MUmol/L) was significantly
      associated with reducing the risk of CAD. Our results support the potential
      cardioprotective impact of coenzyme Q10.

PMID- 22645454
TI  - Natural Interactions between S. haematobium and S. guineensis in the Republic of
      Benin.
AB  - Schistosomiasis is a parasitic disease which affects millions of people around
      the world, particularly in Africa. In this continent, different species are able
      to interbreed, like Schistosoma haematobium and Schistosoma guineensis, two
      schistosome species infecting humans. The Republic of Benin is known to harbor S.
      haematobium, but its geographical situation in between Nigeria, Mali, and Burkina
      Faso, where S. guineensis was found, raises the question about the possible
      presence of S. haematobium/S. guineensis hybrids in this country. We conducted
      morphological analyses on schistosome eggs and molecular analyses on schistosome
      larvae (high resolution melting (HRM) analysis and gene sequencing) in order to
      detect any natural interaction between these two species of schistosomes. The
      morphological results showed the presence of three egg morphotypes (S.
      haematobium, S. guineensis, and intermediate). Three genotypes were detected by
      ITS2 rDNA HRM analysis: S. haematobium, S. guineensis, and hybrid, and their
      percentages confirmed the results of the morphological analysis. However,
      sequencing of the CO1 mtDNA gene showed that all the samples from Benin belonged
      to S. haematobium. Our results provide the first evidence of introgression of S.
      guineensis genes in S. haematobium in Benin.

PMID- 22645456
TI  - Elevation of matrix metalloproteinases in different areas of ascending aortic
      aneurysms in patients with bicuspid and tricuspid aortic valves.
AB  - Our aim is to investigate the elevation of matrix proteins in tissues obtained
      from distal, above the sinotubular junction (proximal), concave, and convex sites
      of aneurysms in the ascending aorta using a simultaneous multiplex protein
      detection system. Tissues were collected from 41 patients with ascending aortic
      aneurysms. A total of 31 patients had a bicuspid aortic valve (BAV), whereas 10
      had a tricuspid aortic valve (TAV). Concave and convex aortic site samples were
      collected from all patients, whereas proximal and distal convexity samples were
      obtained from 19 patients with BAV and 7 patients with TAV. Simultaneous
      detection of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) was
      performed at each of the four aortic sites. MMP-2 levels were higher in the
      concave aortic sites than in the convex aortic sites. In contrast, MMP-8 levels
      were higher in the convex sites than in the concave sites, as were MMP-9 levels.
      In both BAV and TAV patients, TIMP-3 levels were higher in the concave sites than
      in the convex sites. However, TIMP-2 and TIMP-4 levels were significantly
      elevated in the sinotubular proximal aorta of BAV patients. Simultaneous
      detection of MMPs and TIMPs revealed different levels at different aortic sites
      in the same patient.

PMID- 22645455
TI  - Assessment of the prevalence of pulp stones in a sample of Turkish Central
      Anatolian population.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of pulp stones
      (PS) in a Turkish dental patient population with respect to sexes and dental
      localization in relation between sex and this anomaly. MATERIALS METHODS: A
      retrospective study was performed using bitewing radiographs of 814 patients
      ranging in age from 15 to 65. All data (age, sex, and location) was obtained from
      the files. These patients were analyzed for pulp stones. Descriptive
      characteristics of sexes, jaws, and dental localization were recorded. The
      Pearson chi-squared test was used. RESULTS: Of the patients, 462 (56.8%) were
      female and 352 (43.2%) were male. Sixty (12%) had one or more teeth that
      contained pulp stones. Pulp stones were identified in 518 (63.6%) of the subjects
      and in 2391 (27.8%) of the teeth examined. Pulp stone occurrence was
      significantly more common in the females than in males. With the increasing of
      age, the prevalence of pulp stones increased. Molars had statistically more pulp
      stones than premolars. Pulp stones were significantly more common in the maxilla
      compared with mandible. CONCLUSION: Prevalence of pulp stones in Turkish
      population was 27.8% but further larger-scale studies are required to assess its
      prevalence in the general population to compare it with other ethnic groups.

PMID- 22645457
TI  - Low body mass index can identify majority of osteoporotic inflammatory bowel
      disease patients missed by current guidelines.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) are at high risk of
      developing osteoporosis. Our objective was to determine the usefulness of IBD
      guidelines in identifying patients at risk for developing osteoporosis. METHODS:
      We utilized institutional repository to identify patients seen in IBD center and
      extracted data on demographics, disease history, conventional, and
      nonconventional risk factors for osteoporosis and Dual Energy X-ray
      Absorptiometry (DXA) findings. RESULTS: 59% of patients (1004/1703) in our IBD
      cohort had at least one risk factor for osteoporosis screening. DXA was
      documented in 263 patients with indication of screening (provider adherence,
      26.2%), and of these, 196 patients had DXA completed ("at-risk" group). Ninety
      five patients not meeting guidelines-based risk factors also had DXA completed
      ("not at-risk" group). 139 (70.9%) patients in "at-risk" group had low BMD, while
      51 (53.7%) of "not-at-risk" patients had low BMD. Majority of the patients with
      osteoporosis (83.3%) missed by the current guidelines had low BMI. Multivariate
      logistic regression analysis showed that low BMI was the strongest risk factor
      for osteoporosis (OR 3.07; 95% CI, 1.47-6.42; P = 0.003). CONCLUSIONS: Provider
      adherence to current guidelines is suboptimal. Low BMI can identify majority of
      the patients with osteoporosis that are missed by current guidelines.

PMID- 22645458
TI  - Cardiac output and performance during a marathon race in middle-aged recreational
      runners.
AB  - PURPOSE: Despite the increasing popularity of marathon running, there are no data
      on the responses of stroke volume (SV) and cardiac output (CO) to exercise in
      this context. We sought to establish whether marathon performance is associated
      with the ability to sustain high fractional use of maximal SV and CO (i.e,
      cardiac endurance) and/or CO, per meter (i.e., cardiac cost). METHODS: We
      measured the SV, heart rate (HR), CO, and running speed of 14 recreational
      runners in an incremental, maximal laboratory test and then during a real
      marathon race (mean performance: 3 hr 30 min +/- 45 min). RESULTS: Our data
      revealed that HR, SV and CO were all in a high but submaximal steady state during
      the marathon (87.0 +/- 1.6%, 77.2 +/- 2.6%, and 68.7 +/- 2.8% of maximal values,
      respectively). Marathon performance was inversely correlated with an upward drift
      in the CO/speed ratio (mL of CO * m(-1)) (r = -0.65, P < 0.01) and positively
      correlated with the runner's ability to complete the race at a high percentage of
      the speed at maximal SV (r = 0.83, P < 0.0002). CONCLUSION: Our results showed
      that marathon performance is inversely correlated with cardiac cost and
      positively correlated with cardiac endurance. The CO response could be a
      benchmark for race performance in recreational marathon runners.

PMID- 22645459
TI  - Spectroscopic and thermooxidative analysis of organic okra oil and seeds from
      Abelmoschus esculentus.
AB  - With changes in human consumption from animal fats to vegetable oils, the search
      for seed types, often from unconventional vegetable sources has grown. Research
      on the chemical composition of both seed and oil for Brazilian Okra in South
      America is still incipient. In this study, flour and oil from organic Okra seeds
      (Abelmoschus esculentus L Moench), grown in northeastern Brazil were analyzed.
      Similar to Okra varieties from the Middle East and Central America, Brazilian
      Okra has significant amounts of protein (22.14%), lipids (14.01%), and high
      amounts of unsaturated lipids (66.32%), especially the oleic (20.38%) and
      linoleic acids (44.48%). Oil analysis through PDSC revealed an oxidation
      temperature of 175.2  degrees C, which in combination with low amounts of
      peroxide, demonstrates its resistance to oxidation and favors its use for human
      consumption.

PMID- 22645460
TI  - Antinociceptive activity of ethanol extract from Duguetia chrysocarpa Maas
      (Annonaceae).
AB  - The ethanol extract from the fruits of Duguetia chrysocarpa was evaluated for its
      antinociceptive activity in chemical and thermal models of nociception in mice.
      The intraperitoneal administration of the ethanol extract (100, 200, and 400
      mg/kg body weight) showed a dose-dependent inhibition of acetic-acid-induced
      abdominal writhes. The extract also produced a significant inhibition of both
      phases of the formalin test in all doses tested and increased the reaction time
      in hot-plate test at dose of 200 mg/kg. The data obtained suggest that the
      antinociceptive effect of the extract may be mediated via both peripheral and
      central mechanisms. The phytochemical investigation yielded the isolation of the
      benzenoid derivative 3-methoxy-4-ethoxy benzoic acid which is being reported for
      the first time in this genus.

PMID- 22645461
TI  - An optimized real-time PCR to avoid species-/tissue-associated inhibition for
      H5N1 detection in ferret and monkey tissues.
AB  - The real-time PCR diagnostics for avian influenza virus H5N1 in tissue specimens
      are often suboptimal, since naturally occurring PCR inhibitors present in
      samples, or unanticipated match of primer to unsequenced species' genome. With
      the principal aim of optimizing the SYBR Green real-time PCR method for detecting
      H5N1 in ferret and monkey (Chinese rhesus macaque) tissue specimens, we screened
      various H5N1 gene-specific primer pairs and tested their ability to sensitively
      and specifically detect H5N1 transcripts in the infected animal tissues, then we
      assessed RNA yield and quality by comparing Ct values obtained from the standard
      Trizol method, and four commonly used RNA isolation kits with small
      modifications, including Roche High Pure, Ambion RNAqueous, BioMIGA EZgene, and
      Qiagen RNeasy. The results indicated that a single primer pair exhibited high
      specificity and sensitivity for H5N1 transcripts in ferret and monkey tissues.
      Each of the four kits and Trizol reagent produced high-quality RNA and removed
      all or nearly all PCR inhibitors. No statistically significant differences were
      found between the Ct values from the isolation methods. So the optimized SYBR
      Green real-time PCR could avoid species- or tissue-associated PCR inhibition in
      detecting H5N1 in ferret and monkey tissues, including lung and small intestine.

PMID- 22645462
TI  - Animal bones char solubilization by gel-entrapped Yarrowia lipolytica on glycerol
      based media.
AB  - Citric acid was produced with free and k-carrageenan-entrapped cells of the yeast
      Yarrowia lipolytica in single and repeated batch-shake-flask fermentations on
      glycerol-based media. Simultaneous solubilization of hydroxyapatite of animal
      bone origin (HABO) was tested in all experiments. The highest citric acid
      production by free yeast cells of 20.4 g/L and 18.7 g/L was reached after 96 h of
      fermentation in the absence and presence of 3 g/L HABO, respectively. The maximum
      values for the same parameter achieved by gel-entrapped cells in conditions of
      single batch and repeated-batch fermentation processes were 18.7 g/L and 28.1 g/L
      registered after 96 h and the 3d batch cycle, respectively. The highest citric
      acid productivity of 0.58 g L(-1) h(-1) was obtained with immobilized cells in
      repeated batch mode of fermentation when the added hydroxyapatite of 3 g/L was
      solubilized to 399 mg/L whereas the maximum efficiency of 89.0% was obtained with
      1 g/L of HABO.

PMID- 22645463
TI  - Reducing greenhouse gas emissions in grassland ecosystems of the Central
      Lithuania: multi-criteria evaluation on a basis of the ARAS method.
AB  - N(2)O, CH(4), and CO(2) are potential greenhouse gas (GHG) contributing to
      climate change; therefore, solutions have to be sought to reduce their emission
      from agriculture. This work evaluates GHG emission from grasslands submitted to
      different mineral fertilizers during vegetation period (June-September) in two
      experimental sites, namely, seminatural grassland (8 treatments of mineral
      fertilizers) and cultural pasture (intensively managed) in the Training Farm of
      the Lithuanian University of Agriculture. Chamber method was applied for
      evaluation of GHG emissions on the field scale. As a result, soil chemical
      composition, compactness, temperature, and gravimetric moisture as well as
      biomass yield of fresh and dry biomass and botanical composition, were assessed
      during the research. Furthermore, a simulation of multi-criteria assessment of
      sustainable fertilizers management was carried out on a basis of ARAS method. The
      multicriteria analysis of different fertilizing regimes was based on a system of
      environmental and productivity indices. Consequently, agroecosystems of cultural
      pasture (N(180)P(120)K(150)) and seminatural grassland fertilizing rates
      N(180)P(120)K(150) and N(60)P(40)K(50) were evaluated as the most sustainable
      alternatives leading to reduction of emissions between biosphere-atmosphere and
      human-induced biogenic pollution in grassland ecosystems, thus contributing to
      improvement of countryside environment.

PMID- 22645464
TI  - Motion streaks do not influence the perceived position of stationary flashed
      objects.
AB  - In the present study, we investigated whether motion streaks, produced by fast
      moving dots Geisler 1999, distort the positional map of stationary flashed
      objects producing the well-known motion-induced position shift illusion (MIPS).
      The illusion relies on motion-processing mechanisms that induce local distortions
      in the positional map of the stimulus which is derived by shape-processing
      mechanisms. To measure the MIPS, two horizontally offset Gaussian blobs, placed
      above and below a central fixation point, were flashed over two fields of dots
      moving in opposite directions. Subjects judged the position of the top Gaussian
      blob relative to the bottom one. The results showed that neither fast (motion
      streaks) nor slow moving dots influenced the perceived spatial position of the
      stationary flashed objects, suggesting that background motion does not interact
      with the shape-processing mechanisms involved in MIPS.

PMID- 22645465
TI  - Different cardiovascular responses to a resistance training session in
      hypertensive women receiving propanolol compared with normotensive controls.
AB  - The aim of the present study was to compare the responses of blood pressure,
      heart rate, and rate-pressure product of hypertensive women using beta-blockers
      with healthy controls during resistance exercise (by the end of the concentric
      phase of the contractions) and in the postexercise period (5 and 30 minutes
      after). Ten untrained normotensive women (N) and 10 mildly hypertensive females
      receiving 40 mg/day of propanolol (H) were selected. Three sets of 10 repetitions
      at 80% of 10 repetitions maximum with 30 s rest interval were performed on the
      leg press exercise. The H group exhibited lower systolic blood pressure after the
      second set compared with N. Heart rate and rate-pressure product were lower in H
      in all analyzed periods compared with N. Propanolol attenuates the cardiovascular
      response to a leg press resistance exercise in mildly hypertensive women.

PMID- 22645466
TI  - Effect of human and bovine serum albumin on kinetic chemiluminescence of Mn (III)
      Tetrakis (4-sulfonatophenyl) porphyrin-luminol-hydrogen peroxide system.
AB  - The present work deals with an attempt to study the effect of human and bovine
      serum albumin on kinetic parameters of chemiluminescence of luminol-hydrogen
      peroxide system catalyzed by manganese tetrasulfonatophenyl porphyrin (MnTSPP).
      The investigated parameters involved pseudo-first-order rise and fall rate
      constant for the chemiluminescence burst, maximum level intensity, time to reach
      maximum intensity, total light yield, and values of the intensity at maximum CL
      which were evaluated by nonlinear least square program KINFIT. Because of
      interaction of metalloporphyrin with proteins, the CL parameters are drastically
      affected. The systems resulted in Stern-Volmer plots with k(Q) values of 3.17 *
      10(5) and 3.7 * 10(5) M(-1) in the quencher concentration range of 1.5 * 10(-6)
      to 1.5 * 10(-5) M for human serum albumin (HSA) and bovine serum albumin (BSA),
      respectively.

PMID- 22645467
TI  - Trypanosoma cruzi: seroprevalence detection in suburban population of Santiago de
      Queretaro (Mexico).
AB  - OBJECTIVES: To evaluate the potential of iron-oxide dismutase excreted (SODeCRU)
      by T. cruzi as the antigen fraction in the serodiagnosis of Chagas disease and
      compile new epidemiological data on the seroprevalence of this disease in the
      suburban population of the city of Santiago de Queretaro (Mexico). DESIGN AND
      METHODS: 258 human sera were analyzed by the techniques of ELISA and Western blot
      and using the homogenate and the SODeCRU. RESULTS: A total of 31 sera were
      positive against ELISA/SODeCRU (12.4%), while 30 sera proved positive by
      WB/SODeCRU (11.6%). The comparison between the technique of ELISA and WB showed a
      sensitivity of 93%, and a specificity of 99%. The positive predictive value was
      93% and the negative predictive value was 99%, with a Kappa (kappa) value of 1.
      CONCLUSIONS: These preliminary data reveal the degree of infection of nonrural
      areas of Mexico and demonstrated that SODeCRU is an antigen useful to diagnose
      Chagas disease.

PMID- 22645468
TI  - Current status of trace metal pollution in soils affected by industrial
      activities.
AB  - There is a growing public concern over the potential accumulation of heavy metals
      in soil, owing to rapid industrial development. In an effort to describe the
      status of the pollutions of soil by industrial activities, relevant data sets
      reported by many studies were surveyed and reviewed. The results of our analysis
      indicate that soils were polluted most significantly by metals such as lead,
      zinc, copper, and cadmium. If the dominant species are evaluated by the highest
      mean concentration observed for different industry types, the results were
      grouped into Pb, Zn, Ni, Cu, Fe, and As in smelting and metal production
      industries, Mn and Cd in the textile industry, and Cr in the leather industry. In
      most cases, metal levels in the studied areas were found to exceed the common
      regulation guideline levels enforced by many countries. The geoaccumulation index
      (I(geo)), calculated to estimate the enrichment of metal concentrations in soil,
      showed that the level of metal pollution in most surveyed areas is significant,
      especially for Pb and Cd. It is thus important to keep systematic and continuous
      monitoring of heavy metals and their derivatives to manage and suppress such
      pollution.

PMID- 22645470
TI  - Rainfall mechanisms for the dominant rainfall mode over Zimbabwe relative to ENSO
      and/or IODZM.
AB  - Zimbabwe's homogeneous precipitation regions are investigated by means of
      principal component analysis (PCA) with regard to the underlying processes
      related to ENSO and/or Indian Ocean Dipole zonal mode (IODZM). Station
      standardized precipitation index rather than direct rainfall values represent the
      data matrix used in the PCA. The results indicate that the country's rainfall is
      highly homogeneous and is dominantly described by the first principal mode (PC1).
      This leading PC can be used to represent the major rainfall patterns affecting
      the country, both spatially and temporarily. The current practice of subdividing
      the country into the two seasonal rainfall forecast zones becomes irrelevant.
      Partial correlation analysis shows that PC1 is linked more to the IODZM than to
      the traditional ENSO which predominantly demonstrates insignificant association
      with PC1. The pure IODZM composite is linked to the most intense rainfall
      suppression mechanisms, while the pure El Nino composite is linked to rainfall
      enhancing mechanisms.

PMID- 22645469
TI  - Mutation at the human D1S80 minisatellite locus.
AB  - Little is known about the general biology of minisatellites. The purpose of this
      study is to examine repeat mutations from the D1S80 minisatellite locus by
      sequence analysis to elucidate the mutational process at this locus. This is a
      highly polymorphic minisatellite locus, located in the subtelomeric region of
      chromosome 1. We have analyzed 90,000 human germline transmission events and
      found seven (7) mutations at this locus. The D1S80 alleles of the parentage trio,
      the child, mother, and the alleged father were sequenced and the origin of the
      mutation was determined. Using American Association of Blood Banks (AABB)
      guidelines, we found a male mutation rate of 1.04 * 10(-4) and a female mutation
      rate of 5.18 * 10(-5) with an overall mutation rate of approximately 7.77 * 10(
      5). Also, in this study, we found that the identified mutations are in close
      proximity to the center of the repeat array rather than at the ends of the repeat
      array. Several studies have examined the mutational mechanisms of the
      minisatellites according to infinite allele model (IAM) and the one-step stepwise
      mutation model (SMM). In this study, we found that this locus fits into the one
      step mutation model (SMM) mechanism in six out of seven instances similar to STR
      loci.

PMID- 22645471
TI  - Evaluation of the ecochemical status of the Danube in Serbia in terms of water
      quality parameters.
AB  - The Danube is an international river passing partly through Serbia. The
      protection of the environment and sustainable use of water resources is a primary
      task that implies constant monitoring of the quality status and evaluation of
      ecochemical status of the water in the Danube basin. The investigation includes
      calculation of all-inclusive water quality by the Serbian water quality index
      (SWQI) method and an evaluation of eco-chemical status of the Danube water in
      terms of water quality parameters from the entry to the exit point along its
      course through Serbia in the year of 2009. The results show that the overall
      quality of the Danube water on the territory of Serbia corresponds to the
      descriptive indicator of "very good" water. According to the Council
      Directive75/440/EEC, the evaluation of the ecostatus, with slight deviation of
      individual parameters at Pancevo, corresponds to A1 category of the surface water
      quality intended for the abstraction of drinking water supplies in member states.

PMID- 22645472
TI  - Identification of colitis and cancer in colon biopsies by Fourier Transform
      Infrared spectroscopy and chemometrics.
AB  - Cancer is a disease that does great harms to the health of human beings. FT-IR
      spectroscopy could identify variability at the molecular level in biological
      specimens. It is a rapid and noninvasive method, which could be used
      intraoperatively to modify surgical procedures. The aim of this paper is to
      identify and separate cancer from colitis in endoscopic colon biopsies through
      the use of FT-IR spectroscopy. A total of 88 endoscopic colon samples, including
      41 cases of colitis and 47 cases of colon cancer, were obtained. Specimens were
      placed on an ATR accessory linked to FT-IR spectrometer with a MCT detector for
      greater stability and sensitivity. Later, specimens were sent for the
      histological examination as the reference in the spectral analysis. 41 colitis
      and 47 cancer specimens were compared. Spectra preprocessed with smoothing and
      normalization were used for discrimination analysis. PCA was processed to
      simplify the spectrum data set. Naive Bayes classifier model was constructed for
      diagnostic classification. Leave-one-out cross-validation method was utilized to
      assess the discrimination results. The sensitivity of FT-IR detection for cancer
      achieves 97.6%. The results showed that colon cancer could be distinguished from
      colitis with high accuracy using FT-IR spectroscopy and chemometrics.

PMID- 22645473
TI  - Morphostructural characterization of rice grain (Oryza sativa L.) variety Morelos
      A-98 during filling stages.
AB  - The morphostructure of grain rice Morelos A-98 was characterized in five stages
      of physiological maturation, in order to generate morphometric information during
      the filling process. Micrographic images from optical and scanning electron
      microscopy coupled to a digital capture system were used. Images were digitally
      processed to measure different descriptors such as shape, fractal dimension, and
      surface texture. Results showed that, two weeks after anthesis, an accelerated
      grain filling was observed, particularly on those grains positioned in the distal
      panicle zone, compared to those located in the base of this one. As deposition of
      assimilates in the grain increased, the area and perimeter of the transversal cut
      of the grains also increased (P <= 0.05); meanwhile, the rounded shape factor
      tended to increase as well (P <= 0.05), while the elliptic shape factor
      decreased. As the dehydrated endosperm passed from "milky" to "doughy" stages,
      values of fractal dimension area and endosperm perimeter as well as surface
      texture values showed that grain borders tended to become smoother and that there
      was a greater structured endosperm area (P <= 0.05).

PMID- 22645474
TI  - Spectrofluorimetric determination of human serum albumin using terbium
      danofloxacin probe.
AB  - A spectrofluorimetric method is proposed for the determination of human serum
      albumin (HSA) and bovine serum albumin (BSA) using terbium-danofloxacin (Tb(3+)
      Dano) as a fluorescent probe. These proteins remarkably enhance the fluorescence
      intensity of the Tb(3+)-Dano complex at 545 nm, and the enhanced fluorescence
      intensity of Tb(3+)-Dano is proportional to the concentration of proteins (HSA
      and BSA). Optimum conditions for the determination of HSA were investigated and
      found that the maximum response was observed at: pH = 7.8, [Tb(3+)] = 8.5 * 10(
      5) mol L(-1), [Dano] = 1.5 * 10(-4) mol L(-1). The calibration graphs for
      standard solutions of BSA, HSA, and plasma samples of HSA were linear in the
      range of 0.2 * 10(-6) - 1.3 * 10(-6) mol L(-1), 0.2 * 10(-6) - 1.4 * 10(-6) mol
      L(-1), and 0.2 * 10(-6) - 1 * 10(-6) mol L(-1), respectively. The detection
      limits (S/N = 3) for BSA, HSA, and plasma sample of HSA were 8.7 * 10(-8) mol L(
      1), 6.2 * 10(-8) mol L(-1), and 8.1 * 10(-8) mol L(-1), respectively. The
      applicability of the method was checked using a number of real biological plasma
      samples and was compared with the UV spectrometric reference method. The results
      was showed that the method could be regarded as a simple, practical, and
      sensitive alternative method for determination of albumin in biological samples.

PMID- 22645475
TI  - HER-2 expression in immunohistochemistry has no prognostic significance in
      gastric cancer patients.
AB  - The role of HER-2 expression as a prognostic factor in gastric cancer (GC) is
      still controversial. The aim of the study was to asses HER-2 status, its
      correlations with clinicopathological parameters, and prognostic impact in GC
      patients. Tumor samples were collected from 78 patients who had undergone
      curative surgery. In order to evaluate the intensity of immunohistochemical (IHC)
      reactions two scales were applied: the immunoreactive score according to Remmele
      modified by the authors and standardised Hercep test score modified for GC by
      Hofmann et al. The HER-2 overexpression was detected by IHC in 23 (29.5%) tumors
      in Hercep test (score 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4-12). The
      overexpression of HER-2 was associated with poorly differentiated tumors, but
      this correlation was not significant (P = 0.064). No relationship was found
      between HER-2 expression and primary tumor size and degree of spread to regional
      lymph nodes. Both univariate and multivariate analyses revealed that TNM stage
      and patient's age were the crucial negative prognostic factors. No correlation
      was observed between patient survival and expression of HER-2 estimated using
      both scales. This research did not confirm HER-2 expression (evaluated with
      immunohistochemistry) value as a prognostic tool in GC.

PMID- 22645476
TI  - Prostatic relaxation induced by loperamide is reduced in spontaneously
      hypertensive rats.
AB  - This paper shows a new finding about the decrease of relaxative response to
      loperamide in prostate of spontaneously hypertensive rats (SHR) as compare to
      normal rats (WKY). Authors demonstrated the reduction of ATP-sensitive potassium
      channels is responsible for this change using immunoblotting analysis and the
      decrease of action induced by diazoxide. This view is not mentioned before and is
      the first one reporting this result.

PMID- 22645477
TI  - Increased NTPDase activity in lymphocytes during experimental sepsis.
AB  - We investigated in rats induced to sepsis the activity of ectonucleoside
      triphosphate diphosphohydrolase (NTPDase; CD39; E.C. 3.6.1.5), an enzyme involved
      in the modulation of immune responses. After 12 hours of surgery, lymphocytes
      were isolated from blood and NTPDase activity was determined. It was also
      performed the histology of kidney, liver, and lung. The results demonstrated an
      increase in the hydrolysis of adenosine-5'-triphosphate (ATP) (P < 0.01), but no
      changes regarding adenosine-5'-monophosphate (ADP) hydrolysis (P > 0.05).
      Histological analysis showed several morphological changes in the septic group,
      such as vascular congestion, necrosis, and infiltration of mononuclear cells. It
      is known that the intracellular milieu contains much more ATP nucleotides than
      the extracellular. In this context, the increased ATPasic activity was probably
      induced as a dynamic response to clean up the elevated ATP levels resulting from
      cellular death.

PMID- 22645478
TI  - The influence of Kinesio Taping on the effects of physiotherapy in patients after
      laparoscopic cholecystectomy.
AB  - Physiotherapy in patients after laparoscopic cholecystectomy (CHL) is impeded by
      postoperative pain which causes a decline in patients' activity, reduces
      respiratory muscles' function, and affects patients' ability to look after
      themselves. The objective of this work was to assess the influence of Kinesio
      Taping (KT) on pain level and the increase in effort tolerance in patients after
      CHL. The research included 63 patients after CHL. Test group and control group
      included randomly selected volunteers. Control group consisted of 32 patients (26
      females, 6 males), test group consisted of 31 patients (22 females, 9 males).
      Both groups were subjected to complex physiotherapy, and control group had
      additional KT applications. Before surgery, during and after physiotherapy,
      patients were given the following tests: 100-meter walk tests, subjective pain
      perception assessment, and pain relief medicines intake level assessment. The
      level of statistical significance for all tests was established at P < 0.05.
      Statistical analysis showed a significant decrease in the time required to cover
      a 100-meter distance and a decrease in pain perception presented by significantly
      lower painkillers' intake in the test group in comparison with the control group.
      The improvement in clinical condition observed in the research indicates the
      efficiency of KT as a method complementing physiotherapy in patients after
      laparoscopic cholecystectomy.

PMID- 22645479
TI  - Pollen, tapetum, and orbicule development in Colletia paradoxa and Discaria
      americana (Rhamnaceae).
AB  - Tapetum, orbicule, and pollen grain ontogeny in Colletia paradoxa and Discaria
      americana were studied with transmission electron microscopy (TEM). The
      ultrastructural changes observed during the different stages of development in
      the tapetal cells and related to orbicule and pollen grain formation are
      described. The proorbicules have the appearance of lipid globule, and their
      formation is related to the endoplasmic reticulum of rough type (ERr). This is
      the first report on the presence of orbicules in the family Rhamnaceae. Pollen
      grains are shed at the bicellular stage.

PMID- 22645480
TI  - Comparison of thunderstorm simulations from WRF-NMM and WRF-ARW models over East
      Indian Region.
AB  - The thunderstorms are typical mesoscale systems dominated by intense convection.
      Mesoscale models are essential for the accurate prediction of such high-impact
      weather events. In the present study, an attempt has been made to compare the
      simulated results of three thunderstorm events using NMM and ARW model core of
      WRF system and validated the model results with observations. Both models
      performed well in capturing stability indices which are indicators of severe
      convective activity. Comparison of model-simulated radar reflectivity imageries
      with observations revealed that NMM model has simulated well the propagation of
      the squall line, while the squall line movement was slow in ARW. From the model
      simulated spatial plots of cloud top temperature, we can see that NMM model has
      better captured the genesis, intensification, and propagation of thunder squall
      than ARW model. The statistical analysis of rainfall indicates the better
      performance of NMM than ARW. Comparison of model-simulated thunderstorm affected
      parameters with that of the observed showed that NMM has performed better than
      ARW in capturing the sharp rise in humidity and drop in temperature. This
      suggests that NMM model has the potential to provide unique and valuable
      information for severe thunderstorm forecasters over east Indian region.

PMID- 22645481
TI  - Two rare northern Entoloma species observed in Sicily under exceptionally cold
      weather conditions.
AB  - The biology and ecology of many Entoloma species is still poorly known as well as
      their geographical distribution. In Italy, there are no studies on the influence
      of weather on fungal abundance and richness and our knowledge on the ecology and
      distribution of Entoloma species needs to be improved. The discovery of two
      Entoloma species in Sicily (southern Italy), reported in the literature as
      belonging to the habitat of north European countries, was the basis leading to
      the assumption that anomalous climatic conditions could stimulate the growth of
      northern entolomas in the southernmost Mediterranean regions. The results of this
      study show that the presence of northern Entoloma species in Sicily is not
      influenced by the Mediterranean type of vegetation, by edaphic or altitudinal
      factors but by anomalous climatic trends of precipitations and temperatures which
      stimulate the fructification of basidiomata in correspondence with a thermal
      shock during autumn.

PMID- 22645482
TI  - Ultrastructure and glycoconjugate pattern of the foot epithelium of the abalone
      Haliotis tuberculata (Linnaeus, 1758) (Gastropoda, Haliotidae).
AB  - The foot epithelium of the gastropod Haliotis tuberculata is studied by light and
      electron microscopy in order to contribute to the understanding of the anatomy
      and functional morphology of the mollusks integument. Study of the external
      surface by scanning electron microscopy reveals that the side foot epithelium is
      characterized by a microvillus border with a very scant presence of small ciliary
      tufts, but the sole foot epithelium bears a dense field of long cilia.
      Ultrastructural examination by transmission electron microscopy of the side
      epithelial cells shows deeply pigmented cells with high electron-dense granular
      content which are not observed in the epithelial sole cells. Along the pedal
      epithelium, seven types of secretory cells are present; furthermore, two types of
      subepithelial glands are located just in the sole foot. The presence and
      composition of glycoconjugates in the secretory cells and subepithelial glands
      are analyzed by conventional and lectin histochemistry. Subepithelial glands
      contain mainly N-glycoproteins rich in fucose and mannose whereas secretory cells
      present mostly acidic sulphated glycoconjugates such as glycosaminoglycans and
      mucins, which are rich in galactose, N-acetyl-galactosamine, and N-acetyl
      glucosamine. No sialic acid is present in the foot epithelium.

PMID- 22645484
TI  - General analytical schemes for the characterization of pectin-based edible gelled
      systems.
AB  - Pectin-based gelled systems have gained increasing attention for the design of
      newly developed food products. For this reason, the characterization of such
      formulas is a necessity in order to present scientific data and to introduce an
      appropriate finished product to the industry. Various analytical techniques are
      available for the evaluation of the systems formulated on the basis of pectin and
      the designed gel. In this paper, general analytical approaches for the
      characterization of pectin-based gelled systems were categorized into several
      subsections including physicochemical analysis, visual observation,
      textural/rheological measurement, microstructural image characterization, and
      psychorheological evaluation. Three-dimensional trials to assess correlations
      among microstructure, texture, and taste were also discussed. Practical examples
      of advanced objective techniques including experimental setups for small and
      large deformation rheological measurements and microstructural image analysis
      were presented in more details.

PMID- 22645483
TI  - Small cages with insect couples provide a simple method for a preliminary
      assessment of mating disruption.
AB  - Mating disruption by sex pheromones is a sustainable, effective and widely used
      pest management scheme. A drawback of this technique is its challenging
      assessment of effectiveness in the field (e.g., spatial scale, pest density). The
      aim of this work was to facilitate the evaluation of field-deployed pheromone
      dispensers. We tested the suitability of small insect field cages for a pre
      evaluation of the impact of sex pheromones on mating using the grape moths
      Eupoecilia ambiguella and Lobesia botrana, two major pests in vineyards. Cages
      consisted of a cubic metal frame of 35 cm sides, which was covered with a
      mosquito net of 1500 MUm mesh size. Cages were installed in the centre of
      pheromone-treated and untreated vineyards. In several trials, 1 to 20 couples of
      grape moths per cage were released for one to three nights. The proportion of
      mated females was between 15 to 70% lower in pheromone-treated compared to
      untreated vineyards. Overall, the exposure of eight couples for one night was
      adequate for comparing different control schemes. Small cages may therefore
      provide a fast and cheap method to compare the effectiveness of pheromone
      dispensers under standardised semi-field conditions and may help predict the
      value of setting-up large-scale field trials.

PMID- 22645485
TI  - Integration of kinetic analysis of reaction curve with a proper classical
      approach for enzymatic analysis.
AB  - For enzymatic analysis to quantify a substrate or enzyme, kinetic analysis of
      reaction curve can be integrated with a proper classical approach. For their
      integration, they should have consistent slopes and intercepts of linear response
      and an overlapped region of analyte quantities measurable under optimized
      conditions. To quantify a substrate after optimizations of tool enzyme activity
      and reaction duration, the equilibrium method works when the reaction is
      completed within the reaction duration; otherwise, kinetic analysis of reaction
      curve applies providing at least seven data with sufficient consumption of
      substrate. To quantify an enzyme after optimizations of initial substrate
      concentration and reaction duration, the classical initial rate method works when
      an estimated initial rate locates within the linear range; otherwise, kinetic
      analysis of reaction curve applies after the conversion of the quantification
      index with optimized parameters. This integration strategy has ideal linear
      ranges and practical efficiency for quantifying an enzyme at moderate substrate
      levels and for quantifying a substrate at moderate cost on tool enzyme; it has
      promise to simultaneous assays of multiple enzymes in one reaction vessel each
      time and ,thus, potential applications to concurrently quantify multiple serum
      enzymes, screen inhibitors against multiple enzyme targets, and detect multiple
      serum components by enzymeimmunoassay.

PMID- 22645486
TI  - Ephedra alte (joint pine): an invasive, problematic weedy species in forestry and
      fruit tree orchards in Jordan.
AB  - A field survey was carried out to record plant species climbed by Ephedra alte in
      certain parts of Jordan during 2008-2010. Forty species of shrubs, ornamental,
      fruit, and forest trees belonging to 24 plant families suffered from the climbing
      habit of E. alte. Growth of host plants was adversely affected by E. alte growth
      that extended over their vegetation. In addition to its possible competition for
      water and nutrients, the extensive growth it forms over host species prevents
      photosynthesis, smothers growth and makes plants die underneath the extensive
      cover. However, E. alte did not climb all plant species, indicating a host
      preference range. Damaged fruit trees included Amygdalus communis, Citrus
      aurantifolia, Ficus carica, Olea europaea, Opuntia ficus-indica, and Punica
      granatum. Forestry species that were adversely affected included Acacia
      cyanophylla, Ceratonia siliqua, Crataegus azarolus, Cupressus sempervirens, Pinus
      halepensis, Pistacia atlantica, Pistacia palaestina, Quercus coccifera, Quercus
      infectoria, Retama raetam, Rhamnus palaestina, Rhus tripartita, and Zizyphus
      spina-christi. Woody ornamentals attacked were Ailanthus altissima, Hedera helix,
      Jasminum fruticans, Jasminum grandiflorum, Nerium oleander, and Pyracantha
      coccinea. Results indicated that E. alte is a strong competitive for light and
      can completely smother plants supporting its growth. A. communis, F. carica, R.
      palaestina, and C. azarolus were most frequently attacked.

PMID- 22645487
TI  - Climate impacts of deforestation/land-use changes in Central South America in the
      PRECIS regional climate model: mean precipitation and temperature response to
      present and future deforestation scenarios.
AB  - Deforestation/land-use changes are major drivers of regional climate change in
      central South America, impacting upon Amazonia and Gran Chaco ecoregions. Most
      experimental and modeling studies have focused on the resulting perturbations
      within Amazonia. Using the Regional Climate Model PRECIS, driven by ERA-40
      reanalysis and ECHAM4 Baseline model for the period 1961-2000 (40-year runs),
      potential effects of deforestation/land-use changes in these and other
      neighboring ecoregions are evaluated. Current 2002 and estimated 2030 land-use
      scenarios are used to assess PRECIS's response during 1960-2000. ERA-40 and
      ECHAM4 Baseline driven runs yield similar results. Precipitation changes for 2002
      and 2030 land-use scenarios, while significant within deforested areas, do not
      result in significant regional changes. For temperature significant changes are
      found within deforested areas and beyond, with major temperature enhancements
      during winter and spring. Given the current climate, primary effects of
      deforestation/land-use changes remain mostly confined to the tropical latitudes
      of Gran Chaco, and Amazonia.

PMID- 22645488
TI  - Toxic metals enrichment in the surficial sediments of a eutrophic tropical
      estuary (Cochin backwaters, Southwest Coast of India).
AB  - Concentrations and distributions of trace metals (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb,
      and Zn) in surficial sediments of the Cochin backwaters were studied during both
      monsoon and pre-monsoon periods. Spatial variations were in accordance with
      textural charaterstics and organic matter content. A principal component analysis
      distinguished three zones with different metal accumulation capacity: (i) highest
      levels in north estuary, (ii) moderate levels in central zone, and (iii) lowest
      levels in southern part. Trace metal enrichments are mainly due to anthropogenic
      contribution of industrial, domestic, and agricultural effluents, whose effect is
      enhanced by settling of metals due to organic flocculation and inorganic
      precipitation associated with salinity changes. Enrichments factors using Fe as a
      normalizer showed that metal contamination was the product of anthropogenic
      activities. An assessment of degree of pollution-categorized sediments as
      moderately polluted with Cu and Pb, moderately-to-heavily polluted with Zn, and
      heavily-to-extremely polluted with Cd. Concentrations at many sites largely
      exceed NOAA ERL (e.g., Cu, Cr, and Pb) or ERM (e.g., Cd, Ni, and Zn). This means
      that adverse effects for benthic organisms are possible or even highly probable.

PMID- 22645489
TI  - Use of fertigation and municipal solid waste compost for greenhouse pepper
      cultivation.
AB  - Municipal solid waste compost (MSWC) and/or fertigation used in greenhouse pepper
      (Capsicum annuum L.) cultivation with five different substrates with soil (S)
      and/or MSWC mixtures (0-5-10-20-40%) used with or without fertigation. Plants
      growth increased in 10-20% MSWC and fertigation enhanced mainly the plant height.
      Fruit number increased in S : MSWC 80 : 20 without fertilizer. Plant biomass
      increased as MSWC content increased. There were no differences regarding leaf
      fluoresces and plant yield. The addition of MSWC increased nutritive value (N, K,
      P, organic matter) of the substrate resulting in increased EC. Fruit fresh weight
      decreased (up to 31%) as plants grown in higher MSWC content. Fruit size
      fluctuated when different MSWC content used into the soil and the effects were
      mainly in fruit diameter rather than in fruit length. Interestingly, the scale of
      marketable fruits reduced as MSWC content increased into the substrate but
      addition of fertilizer reversed this trend and maintained the fruit
      marketability. MSWC affected quality parameters and reduced fruit acidity, total
      phenols but increased fruit lightness. No differences observed in fruit dry
      matter content, fruit firmness, green colour, total soluble sugars and EC of
      peppers and bacteria (total coliform and E. coli) units. Low content of MSWC
      improved plant growth and maintained fruit fresh weight for greenhouse pepper
      without affecting plant yield, while fertigation acted beneficially.

PMID- 22645490
TI  - Effects of visual deprivation on gait dynamic stability.
AB  - Vision can improve bipedal upright stability during standing and affect
      spatiotemporal parameters during walking. However, little is known about the
      effects of visual deprivation on gait dynamic stability. We have tested 28
      subjects during walking under two different visual conditions, full vision (FV)
      and no vision (NV), measuring their upper body accelerations. Lower accelerations
      were found in NV for the reduced walking speed. However, the normalized
      accelerations were higher in the NV than in the FV condition, both in
      anteroposterior (1.05 +/- 0.21 versus 0.88 +/- 0.16, P = 0.001) and laterolateral
      (0.99 +/- 0.26 versus 0.78 +/- 0.19, P < 0.001) directions. Vision also affected
      the gait anteroposterior harmony (P = 0.026) and, interacting with the
      environment, also the latero-lateral one (P = 0.017). Directly (as main factor of
      the ANOVA) or indirectly (by means of significant interactions with other
      factors), vision affected all the measured parameters. In conclusion,
      participants showed an environment-dependent reduction of upper body stability
      and harmony when deprived by visual feedback.

PMID- 22645492
TI  - Application of HPLC combined with laser induced fluorescence for protein profile
      analysis of tissue homogenates in cervical cancer.
AB  - A highly objective method, High Performance Liquid Chromatography with Laser
      Induced Fluorescence (HPLC-LIF) technique was used to study the protein profiles
      of normal and cervical cancer tissue homogenates. A total of 44 samples including
      normal cervical biopsy samples from the hysterectomy patients and the patients
      suffering from different stages of the cervical cancer were recorded by HPLC-LIF
      and analysed by Principle Component Analysis (PCA) to get statistical information
      on different tissue components. Discrimination of different stages of the samples
      was carried out by considering three parameters--scores of factor, spectral
      residual, and Mahalanobis Distance. Diagnostic accuracy of the method was
      evaluated using Receiver Operating Characteristic (ROC) analysis, and Youden's
      index (J) plots. The PCA results showed high sensitivity and specificity (~100)
      for cervical cancer diagnosis. ROC and Youden's index curves for both normal and
      malignant standard sets show good diagnostic accuracy with high AUC values. The
      statistical analysis has shown that the differences in protein profiles can be
      used to diagnose biochemical changes in the tissue, and thus can be readily
      applied for the detection of cervical cancer, even in situations where a
      histopathology examination is not easy because of nonavailability of experienced
      pathologists.

PMID- 22645491
TI  - A genetic approach to Spanish populations of the threatened Austropotamobius
      italicus located at three different scenarios.
AB  - Spanish freshwater ecosystems are suffering great modification and some
      macroinvertebrates like Austropotamobius italicus, the white-clawed crayfish, are
      threatened. This species was once widely distributed in Spain, but its
      populations have shown a very strong decline over the last thirty years, due to
      different factors. Three Spanish populations of this crayfish--from different
      scenarios--were analysed with nuclear (microsatellites) and mitochondrial markers
      (COI and 16S rDNA). Data analyses reveal the existence of four haplotypes at
      mitochondrial level and polymorphism for four microsatellite loci. Despite this
      genetic variability, bottlenecks were detected in the two natural Spanish
      populations tested. In addition, the distribution of the mitochondrial haplotypes
      and SSR alleles show a similar geographic pattern and the genetic differentiation
      between these samples is mainly due to genetic drift. Given the current risk
      status of the species across its range, this diversity offers some hope for the
      species from a management point of view.

PMID- 22645493
TI  - Concomitant administration of different doses of simvastatin with ivabradine
      influence on PAI-1 and heart rate in normo- and hypercholesterolaemic rats.
AB  - Ivabradine is a novel heart rate lowering agent that inhibits I(f) ionic current
      in the sinus node and demonstrates antiischaemic and antianginal activity. The
      aim of the paper was to investigate the effect its dose-dependent drug-drug
      interaction with simvastatin inhibitor HMGCo-A has on PAI-1 blood level, heart
      rate and blood pressure. The experiments were performed in hyper- and
      normocholesterolemic Wistar rats receiving simvastatin (1 and 20 mg * kg(-1) bw)
      with ivabradine (10 mg * kg(-1) bw) during a 4-week period. Ivabradine
      exacerbated the decrease of PAI-1 in normocholesterolemic animals receiving
      simvastatin at a dose of 1 mg/kg bw and was not observed to have any significant
      influence on the PAI-1 values in rats receiving 20 mg * kg(-1) bw simvastatin.
      Ivabradine, coadministered with simvastatin given at a dose of 20 mg * kg(-1) bw,
      significantly slowed the heart rate in normocholesterolaemic and
      hypercholesterolaemic groups as compared to the group receiving ivabradine alone.
      Conclusion. The administration of ivabradine to normocholesterolaemic and
      hypercholesterolaemic rats receiving simvastatin significantly exacerbated the
      slowing of heart rate with no effect on blood pressure. The administration of
      ivabradine has been shown to demonstrate different effects on PAI-1 values
      depending on lipid disorders.

PMID- 22645494
TI  - Availability, use, and cultivation of support networks as predictors of the well
      being of middle-aged and older Chinese: a panel study.
AB  - OBJECTIVES: To examine the impact of the availability, use, and cultivation of a
      support network on the well-being of community-dwelling, middle-aged, and older
      Chinese. METHODS: A total of 2,970 Hong Kong Chinese aged 40-74 years were
      interviewed using a structured questionnaire in 2004. Out of the original group
      of interviewees, 2,120 (71.4%) were interviewed again in 2005. RESULTS:
      Structural equation modeling revealed a good fit of the model employing Wave 1
      support network data and demographic characteristics to predict Wave 2 well
      being. As hypothesized, the availability of important social ties and the
      cultivation of one's support networks were found to predict well-being one year
      later, but not the use of support networks to meet emotional, financial, or
      companion needs after controlling for demographic variables and baseline well
      being. DISCUSSION: Cultivating support networks can be interpreted as positive
      and active coping. Such cultivation is in line with what socioemotional
      selectivity theory predicts; specifically, when people age, they become more
      selective and concentrate on strengthening their relationship with those they are
      emotionally close to. We argue that network cultivation deserves more attention
      in theory, practice, and research to strengthen the resilience and adaptability
      of individuals approaching and experiencing old age.

PMID- 22645495
TI  - Evolutionary pattern of Asian HIV-1 subtype B from 1990 to 2007: in silico
      analysis based on envelop protein.
AB  - HIV-1 envelop gene is a major target for vaccine development. Envelop protein and
      its V3 loop is shown to be important determinant of HIV-1 pathogenecity. Herein,
      the evolutionary pattern of most prevalent HIV-1 subtype B in Asia is determined
      by analyzing envelop protein and V3 domain based on the 40 randomly selected
      sequences of HIV-1 from database (Los Alamos), divided into four groups since
      1990-2007. Construction of envelop protein phylogeny by using MEGA 5 exhibit the
      active mutation pattern, increase in potential N-glycosylation sites which were
      predicted by using online software SignalP-NN. An online available tool Drawgram
      was used for multiple sequence alignment (MSA) of HIV-1 subtype B envelop region
      and V3 loop while the alignment was rechecked by using CLUSTAL W and further was
      analyzed for GPGX motif and conserved region in V3 loop. Variation at fourth
      position of the GPGX motif and 60% conservation was found in V3 loop. Hence, this
      diversifying pattern of envelop protein in the Asia formulates the HIV-1 strains
      more pathogenic during the period of 17 years. These findings might help in
      understanding significant structural and functional constrains of the mutant
      viral strains and ultimately in vaccine development.

PMID- 22645496
TI  - Influence of codon bias on heterologous production of human papillomavirus type
      16 major structural protein L1 in yeast.
AB  - Heterologous gene expression is dependent on multistep processes involving
      regulation at the level of transcription, mRNA turnover, protein translation, and
      posttranslational modifications. Codon bias has a significant influence on
      protein yields. However, sometimes it is not clear which parameter causes
      observed differences in heterologous gene expression as codon adaptation
      typically optimizes many sequence properties at once. In the current study, we
      evaluated the influence of codon bias on heterologous production of human
      papillomavirus type 16 (HPV-16) major structural protein L1 in yeast by
      expressing five variants of codon-modified open reading frames (OFRs) encoding
      HPV-16 L1 protein. Our results showed that despite the high toleration of various
      codons used throughout the length of the sequence of heterologously expressed
      genes in transformed yeast, there was a significant positive correlation between
      the gene's expression level and the degree of its codon bias towards the
      favorable codon usage. The HPV-16 L1 protein expression in yeast can be optimized
      by adjusting codon composition towards the most preferred codon adaptation, and
      this effect most probably is dependent on the improved translational elongation.

PMID- 22645497
TI  - Experimental infection and detection of necrotizing hepatopancreatitis bacterium
      in the American lobster Homarus americanus.
AB  - Necrotizing hepatopancreatitis bacterium (NHPB) is an obligated intracellular
      bacteria causing severe hepatopancreatic damages and mass mortalities in penaeid
      shrimp. The worldwide distribution of penaeid shrimp as alien species threatens
      the life cycle of other crustacean species. The aim of the experiment was to
      evaluate the possibility of experimentally infecting the American lobster
      (Homarus americanus) with NHPB extracted from shrimp hepatopancreas. Homogenates
      from infected shrimp were fed by force to lobsters. Other group of lobsters was
      fed with homogenates of NHPB-free hepatopancreas. After the 15th day from initial
      inoculation, the presence of NHPB was detected by polymerase chain reaction in
      feces and hepatopancreas from lobsters inoculated with infected homogenates.
      Necrotized spots were observed in the surface of lobster hepatopancreas. In
      contrast, lobsters fed on NHPB-free homogenates resulted negative for NHPB.
      Evidence suggests the plasticity of NHPB which can infect crustacean from
      different species and inhabiting diverse latitudes. Considering the results, the
      American lobster could be a good candidate to maintain available NHPB in vivo.

PMID- 22645498
TI  - Modeling rainfall variability over urban areas: a case study for Kuwait.
AB  - This study examines the spatial and temporal variability of monthly total
      rainfall data obtained from weather stations located in the urban areas of
      Kuwait. The rainfall data are analyzed by considering statistics on a seasonal
      basis and by means of periodogram technique to reveal the periods responsible for
      the variable pattern. The results demonstrate similarity implying that a point
      estimate of rainfall data can be considered spatially representative over the
      urban areas of Kuwait. A sinusoidal model triggering the influence of the
      detected periods is developed accordingly for the time duration from January 1965
      to December 2009. The model is capable of describing the rainfall data with some
      discrepancies between the actual and calculated values resulting from hidden
      periods that have not been taken into account. This finding suggests that the
      ability to construct a more reliable model would require a wider range of
      historical data to detect the other periods affecting the rainfall pattern.

PMID- 22645499
TI  - Mechanistic framework for establishment, maintenance, and alteration of cell
      polarity in plants.
AB  - Cell polarity establishment, maintenance, and alteration are central to the
      developmental and response programs of nearly all organisms and are often
      implicated in abnormalities ranging from patterning defects to cancer. By
      residing at the distinct plasma membrane domains polar cargoes mark the
      identities of those domains, and execute localized functions. Polar cargoes are
      recruited to the specialized membrane domains by directional secretion and/or
      directional endocytic recycling. In plants, auxin efflux carrier PIN proteins
      display polar localizations in various cell types and play major roles in
      directional cell-to-cell transport of signaling molecule auxin that is vital for
      plant patterning and response programs. Recent advanced microscopy studies
      applied to single cells in intact plants reveal subcellular PIN dynamics. They
      uncover the PIN polarity generation mechanism and identified important roles of
      AGC kinases for polar PIN localization. AGC kinase family members PINOID, WAG1,
      and WAG2, belonging to the AGC-3 subclass predominantly influence the polar
      localization of PINs. The emerging mechanism for AGC-3 kinases action suggests
      that kinases phosphorylate PINs mainly at the plasma membrane after initial
      symmetric PIN secretion for eventual PIN internalization and PIN sorting into
      distinct ARF-GEF-regulated polar recycling pathways. Thus phosphorylation status
      directs PIN translocation to different cell sides. Based on these findings a
      mechanistic framework evolves that suggests existence of cell side-specific
      recycling pathways in plants and implicates AGC3 kinases for differential PIN
      recruitment among them for eventual PIN polarity establishment, maintenance, and
      alteration.

PMID- 22645500
TI  - Antioxidant protection against curative and palliative doses of ionizing
      irradiation in human blood decreases with aging.
AB  - Reactive oxygen species (ROS) are independently recognized to play a significant
      role in radiation-induced damage on healthy tissue and in aging process. However,
      an age-related alteration of antioxidant (AO) system in radiation response in
      humans is poorly investigated. The aim of this paper was to evaluate the
      irradiation effects on the activities and expression of AO system in the blood of
      healthy women during aging. Blood samples were irradiated with curative and
      palliative doses of 2 Gy or 9 Gy gamma-rays. AO capacity for detoxification of
      O(2)*(-) and H(2)O(2) in response to 2 Gy gamma-irradiation decreases in women
      above 58 years, while in response to 9 Gy shows signs of weakening after 45 years
      of age. Due to reduction of AO capacity during aging, cytotoxic effects of
      curative and palliative doses of irradiation, mediated by ROS, may significantly
      increase in older subjects, while removal of H(2)O(2) excess could reduce them.

PMID- 22645501
TI  - Zinc affects differently growth, photosynthesis, antioxidant enzyme activities
      and phytochelatin synthase expression of four marine diatoms.
AB  - Zinc-supplementation (20 MUM) effects on growth, photosynthesis, antioxidant
      enzyme activities (superoxide dismutase, ascorbate peroxidase, catalase), and the
      expression of phytochelatin synthase gene were investigated in four marine
      diatoms (Amphora acutiuscula, Nitzschia palea, Amphora coffeaeformis and
      Entomoneis paludosa). Zn-supplementation reduced the maximum cell density. A
      linear relationship was found between the evolution of gross photosynthesis and
      total chlorophyll content. The Zn treatment decreased the electron transport rate
      except in A. coffeaeformis and in E. paludosa at high irradiance. A linear
      relationship was found between the efficiency of light to evolve oxygen and the
      size of the light-harvesting antenna. The external carbonic anhydrase activity
      was stimulated in Zn-supplemented E. paludosa but was not correlated with an
      increase of photosynthesis. The total activity of the antioxidant enzymes did not
      display any clear increase except in ascorbate peroxidase activity in N. palea.
      The phytochelatin synthase gene was identified in the four diatoms, but its
      expression was only revealed in N. palea, without a clear difference between
      control and Zn-supplemented cells. Among the four species, A. paludosa was the
      most sensitive and A. coffeaeformis, the most tolerant. A. acutiuscula seemed to
      be under metal starvation, whereas, to survive, only N. palea developed several
      stress responses.

PMID- 22645502
TI  - Evidence for directed evolution of larger size motif in Arabidopsis thaliana
      genome.
AB  - Transcription control of gene expression depends on a variety of interactions
      mediated by the core promoter region, sequence specific DNA-binding proteins, and
      their cognate promoter elements. The prominent group of cis acting elements in
      plants contains an ACGT core. The cis element with this core has been shown to be
      involved in abscisic acid, salicylic acid, and light response. In this study,
      genome-wide comparison of the frequency of occurrence of two ACGT elements
      without any spacers as well as those separated by spacers of different length was
      carried out. In the first step, the frequency of occurrence of the cis element
      sequences across the whole genome was determined by using BLAST tool. In another
      approach the spacer sequence was randomized before making the query. As expected,
      the sequence ACGTACGT had maximum occurrence in Arabidopsis thaliana genome. As
      we increased the spacer length, one nucleotide at a time, the probability of its
      occurrence in genome decreased. This trend continued until an unexpectedly sharp
      rise in frequency of (ACGT)N25(ACGT). The observation of higher probability of
      bigger size motif suggests its directed evolution in Arabidopsis thaliana genome.

PMID- 22645503
TI  - Alveolar overdistension as a cause of lung injury: differences among three animal
      species.
AB  - This study analyses characteristics of lung injuries produced by alveolar
      overdistension in three animal species. Mechanical ventilation at normal tidal
      volume (10 mL/Kg) and high tidal volume (50 mL/Kg) was applied for 30 min in each
      species. Data were gathered on wet/dry weight ratio, histological score, and area
      of alveolar collapse. Five out of six rabbits with high tidal volume developed
      tension pneumothorax, and the rabbit results were therefore not included in the
      histological analysis. Lungs from the pigs and rats showed minimal histological
      lesions. Pigs ventilated with high tidal volume had significantly greater oedema,
      higher neutrophil infiltration, and higher percentage area of alveolar collapse
      than rats ventilated with high tidal volume. We conclude that rabbits are not an
      appropriate species for in vivo studies of alveolar overdistension due to their
      fragility. Although some histological lesions are observed in pigs and rats, the
      lesions do not appear to be relevant.

PMID- 22645504
TI  - Ultrasound-assisted emulsification microextraction based on solidification
      floating organic drop trace amounts of manganese prior to graphite furnace atomic
      absorption spectrometry determination.
AB  - In the present study, an ultrasound-assisted emulsification microextraction based
      on solidification floating organic drop method is described for preconcentration
      of trace amounts of Mn (II). 2-(5-Bromo-2-pyridylazo)-5 diethylaminophenol was
      added to a solution of Mn(+2) at ph = 10.0. After this, 1-undecanol was added to
      the solution as an extraction solvent, and solution was stirred. Several factors
      influencing the microextraction efficiency, such as pH, the amount of chelating
      agent, nature and volume of extraction solvent, the volume of sample solution,
      stirring rate, and extraction time were investigated and optimized. Then sample
      vial was cooled by inserting into an ice bath, and the solidified was transferred
      into a suitable vial for immediate melting. Finally the sample was injected into
      a graphite furnace atomic absorption spectrometry. Under the optimum condition
      the linear dynamic range was 0.50-10.0 ng mL(-1) with a correlation coefficient
      of 0.9926, and the detection limit of 0.3 ng mL(-1) was obtained. The enrichment
      factor was 160. The proposed method was successfully applied for separation and
      determination of manganese in sea, rain, tap, and river water samples.

PMID- 22645505
TI  - Patients within the Broad Holoprosencephaly Spectrum have Distinct and Subtle
      Ophthalmologic Anomalies: Response to Khan.

PMID- 22645506
TI  - Grand challenges in pediatric endocrinology.

PMID- 22645507
TI  - Mode of action and functional significance of 7alpha-hydroxypregnenolone
      stimulating locomotor activity.
AB  - Previous studies over the past two decades have demonstrated that the brain and
      other nervous systems possess key steroidogenic enzymes and produces pregnenolone
      and other various neurosteroids in vertebrates in general. Recently, 7alpha
      hydroxypregnenolone, a novel bioactive neurosteroid, was identified in the brain
      of newts and quail. Importantly, this novel neurosteroid is produced from
      pregnenolone through the enzymatic activity of cytochrome P450(7alpha) and acts
      on brain tissue as a neuronal modulator to stimulate locomotor activity in these
      vertebrates. Subsequently, the mode of action of 7alpha-hydroxypregnenolone was
      demonstrated. 7alpha-Hydroxypregnenolone stimulates locomotor activity through
      activation of the dopaminergic system. To understand the functional significance
      of 7alpha-hydroxypregnenolone in the regulation of locomotor activity, diurnal,
      and seasonal changes in 7alpha-hydroxypregnenolone synthesis were further
      characterized. Melatonin derived from the pineal gland and eyes regulates 7alpha
      hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor
      changes. Prolactin, an adenohypophyseal hormone, regulates 7alpha
      hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor
      changes. In addition, 7alpha-hydroxypregnenolone mediates corticosterone action
      to modulate locomotor activity under stress. This review summarizes the current
      knowledge regarding the mode of action and functional significance of 7alpha
      hydroxypregnenolone, a newly identified bioactive neurosteroid stimulating
      locomotor activity.

PMID- 22645508
TI  - Sex differences in brain aromatase activity: genomic and non-genomic controls.
AB  - Aromatization of testosterone into estradiol in the preoptic area plays a
      critical role in the activation of male copulation in quail and in many other
      vertebrate species. Aromatase expression in quail and in other birds is higher
      than in rodents and other mammals, which has facilitated the study of the
      controls and functions of this enzyme. Over relatively long time periods (days to
      months), brain aromatase activity (AA), and transcription are markedly (four- to
      sixfold) increased by genomic actions of sex steroids. Initial work indicated
      that the preoptic AA is higher in males than in females and it was hypothesized
      that this differential production of estrogen could be a critical factor
      responsible for the lack of behavioral activation in females. Subsequent studies
      revealed, however, that this enzymatic sex difference might contribute but is not
      sufficient to explain the sex difference in behavior. Studies of AA,
      immunoreactivity, and mRNA concentrations revealed that sex differences observed
      when measuring enzymatic activity are not necessarily observed when one measures
      mRNA concentrations. Discrepancies potentially reflect post-translational
      controls of the enzymatic activity. AA in quail brain homogenates is rapidly
      inhibited by phosphorylation processes. Similar rapid inhibitions occur in
      hypothalamic explants maintained in vitro and exposed to agents affecting
      intracellular calcium concentrations or to glutamate agonists. Rapid changes in
      AA have also been observed in vivo following sexual interactions or exposure to
      short-term restraint stress and these rapid changes in estrogen production
      modulate expression of male sexual behaviors. These data suggest that brain
      estrogens display most if not all characteristics of neuromodulators if not
      neurotransmitters. Many questions remain however concerning the mechanisms
      controlling these rapid changes in estrogen production and their behavioral
      significance.

PMID- 22645509
TI  - Neurosteroid biosynthesis and function in the brain of domestic birds.
AB  - It is now established that the brain and other nervous systems have the
      capability of forming steroids de novo, the so-called "neurosteroids." The
      pioneering discovery of Baulieu and his colleagues, using rodents, has opened the
      door to a new research field of "neurosteroids." In contrast to mammalian
      vertebrates, little has been known regarding de novo neurosteroidogenesis in the
      brain of birds. We therefore investigated neurosteroid formation and metabolism
      in the brain of quail, a domestic bird. Our studies over the past two decades
      demonstrated that the quail brain possesses cytochrome P450 side-chain cleavage
      enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase
      (3beta-HSD), 5beta-reductase, cytochrome P450 17alpha-hydroxylase/c17,20-lyase
      (P450(17alpha,lyase)), 17beta-HSD, etc., and produces pregnenolone, progesterone,
      5beta-dihydroprogesterone (5beta-DHP), 3beta, 5beta-tetrahydroprogesterone
      (3beta, 5beta-THP), androstenedione, testosterone, and estradiol from
      cholesterol. Independently, Schlinger's laboratory demonstrated that the brain of
      zebra finch, a songbird, also produces various neurosteroids. Thus, the formation
      and metabolism of neurosteroids from cholesterol is now known to occur in the
      brain of birds. In addition, we recently found that the quail brain expresses
      cytochrome P450(7alpha) and produces 7alpha- and 7beta-hydroxypregnenolone,
      previously undescribed avian neurosteroids, from pregnenolone. This paper
      summarizes the advances made in our understanding of neurosteroid formation and
      metabolism in the brain of domestic birds. This paper also describes what are
      currently known about physiological changes in neurosteroid formation and
      biological functions of neurosteroids in the brain of domestic and other birds.

PMID- 22645511
TI  - Long term sequelae of pediatric craniopharyngioma - literature review and 20
      years of experience.
AB  - Craniopharyngioma are rare histologically benign brain tumors that develop in the
      pituitary-hypothalamic area. They may invade nearby anatomical structures causing
      significant rates of neurological, neurocognitive, and endocrinological
      complications including remarkable hypothalamic damage. Information regarding
      long term implications of the tumors and treatment in the pediatric population is
      accumulating, and treatment goals appear to be changing accordingly. In this
      review we aim to present data regarding long term complications of
      craniopharyngioma in children and adolescents and our experience from a large
      tertiary center. Hypothalamic dysfunction was noted to be the most significant
      complication, adversely affecting quality of life in survivors. Obesity, fatigue,
      and sleep disorders are the most notable manifestations of this dysfunction, and
      treatment is extremely difficult. Changes in management in recent years show a
      potential for improved long term outcomes; we found a trend toward less
      aggressive surgical management and increasing use of adjuvant treatment,
      accompanied by a decrease in complication rates.

PMID- 22645510
TI  - Beyond Leptin: Emerging Candidates for the Integration of Metabolic and
      Reproductive Function during Negative Energy Balance.
AB  - Reproductive status is tightly coupled to metabolic state in females, and ovarian
      cycling in mammals is halted when energy output exceeds energy input, a metabolic
      condition known as negative energy balance. This inhibition of reproductive
      function during negative energy balance occurs due to suppression of gonadotropin
      releasing hormone (GnRH) release in the hypothalamus. The GnRH secretagogue
      kisspeptin is also inhibited during negative energy balance, indicating that
      inhibition of reproductive neuroendocrine circuits may occur upstream of GnRH
      itself. Understanding the metabolic signals responsible for the inhibition of
      reproductive pathways has been a compelling research focus for many years. A
      predominant theory in the field is that the status of energy balance is conveyed
      to reproductive neuroendocrine circuits via the adipocyte hormone leptin. Leptin
      is stimulatory for GnRH release and lower levels of leptin during negative energy
      balance are believed to result in decreased stimulatory drive for GnRH cells.
      However, recent evidence found that restoring leptin to physiological levels did
      not restore GnRH function in three different models of negative energy balance.
      This suggests that although leptin may be an important permissive signal for
      reproductive function as indicated by many years of research, factors other than
      leptin must critically contribute to negative energy balance-induced reproductive
      inhibition. This review will focus on emerging candidates for the integration of
      metabolic status and reproductive function during negative energy balance.

PMID- 22645512
TI  - Papillary thyroid carcinoma and inflammation.

PMID- 22645513
TI  - THP-1 Macrophages and SGBS Adipocytes - A New Human in vitro Model System of
      Inflamed Adipose Tissue.
AB  - Obesity is associated with an accumulation of macrophages in adipose tissue. This
      inflammation of adipose tissue is a key event in the pathogenesis of several
      obesity-related disorders, particularly insulin resistance. Here, we summarized
      existing model systems that mimic the situation of inflamed adipose tissue in
      vitro, most of them being murine. Importantly, we introduce our newly established
      human model system which combines the THP-1 monocytic cell line and the
      preadipocyte cell strain Simpson-Golabi-Behmel syndrome (SGBS). THP-1 cells,
      which originate from an acute monocytic leukemia, differentiate easily into
      macrophages in vitro. The human preadipocyte cell strain SGBS was recently
      introduced as a unique tool to study human fat cell functions. SGBS cells are
      characterized by a high capacity for adipogenic differentiation. SGBS adipocytes
      are capable of fat cell-specific metabolic functions such as insulin-stimulated
      glucose uptake, insulin-stimulated de novo lipogenesis and beta-adrenergic
      stimulated lipolysis and they secrete typical adipokines including leptin,
      adiponectin, and RBP4. Applying either macrophage-conditioned medium or a direct
      co-culture of macrophages and fat cells, our model system can be used to
      distinguish between paracrine and cell-contact dependent effects. In conclusion,
      we propose this model as a useful tool to study adipose inflammation in vitro. It
      represents an inexpensive, highly reproducible human system. The methods
      described here can be easily extended for usage of primary human macrophages and
      fat cells.

PMID- 22645514
TI  - Surgical strategies in childhood craniopharyngioma.
AB  - Craniopharyngiomas are biologically benign lesions (WHO Grade 1) of the sellar
      and suprasellar region, associated with a serious morbidity. About 50% of these
      tumors become clinically apparent during childhood. Clinical symptoms include
      headaches, chiasm syndrome, hydrocephalus, pituitary insufficiencies, and
      obesity. Growth arrest is a typical symptom in children. The treatment of
      craniopharyngiomas includes surgery as well as radiotherapy. The goal of surgery
      varies according to the tumor location and extension and may range from complete
      resection to biopsy. Surgical complications are well known and cause constant
      evaluation of surgical strategies. Diencephalic obesity is related to surgical
      manipulation of hypothalamic tissue. Therefore, a classification system for
      craniopharyngiomas based on preoperative MRI is suggested by the authors.
      Recurrences are frequent in craniopharyngiomas, even after complete or gross
      total resection. Radiotherapy is therefore recommended to patients with
      incomplete resections. However, the ideal time for radiotherapy after surgery is
      under discussion. The treatment of craniopharyngiomas requires an
      interdisciplinary and multimodal approach. Each patient should receive an
      individually tailored treatment. Surgically, different approaches as well as
      different degrees of resection can be considered, depending on tumor location and
      tumor extension.

PMID- 22645516
TI  - Season of birth and the risk of hip fracture in danish men and women aged 65+.
AB  - Vitamin D status in pregnant women has been linked to childhood bone mineral
      density in their offspring but it is unclear if effects extend to fracture risk
      in adulthood or even old age. As vitamin D levels in the population show
      pronounced seasonal variation in Denmark, we performed an epidemiological
      analysis of hip fracture rates as a function of season of birth, age, and sex. We
      retrieved information on all hip fractures in the 9-year period between 1997 and
      2005 in all men and women aged 65-95, excluded hip fractures that occurred in
      current and recent prednisolone users, and subsequently calculated fracture rates
      and relative risks. The analysis covered 541,109 men and 691,522 women. In women,
      we observed a small but statistically significant difference between fracture
      rates by season of birth for all age intervals expect the youngest (age 65-69). A
      similar pattern was seen in men, but this was only statistically significant in
      the two oldest age groups (age 85-89 and 90-95). These findings suggest that
      vitamin D availability in the first and second trimester of intrauterine life
      could have a small but lasting impact on bone health and the risk of osteoporotic
      fractures. Further studies are needed.

PMID- 22645515
TI  - Recent topics on the regulatory mechanism of ecdysteroidogenesis by the
      prothoracic glands in insects.
AB  - Molting and metamorphosis are strictly regulated by steroid hormones known as
      ecdysteroids. It is now widely recognized that ecdysteroid biosynthesis
      (ecdysteroidogenesis) in the prothoracic gland (PG) is regulated by the tropic
      factor prothoracicotropic hormone (PTTH). However, the importance of PTTH in the
      induction of molting and metamorphosis remains unclear, and other mechanisms are
      thought to be involved in the regulation of ecdysteroidogenesis by the PG.
      Recently, new regulatory mechanisms, prothoracicostatic factors, and neural
      regulation have been explored using the silkworm, Bombyx mori, and two
      circulating prothoracicostatic factors, prothoracicostatic peptide (PTSP) and
      Bommo-myosuppressin (BMS), have been identified. Whereas PTTH and BMS are
      secreted from the brain, PTSP is secreted from the peripheral neurosecretory
      system - the epiproctodeal gland - during the molting stage. The molecular basis
      of neural regulation of ecdysteroidogenesis has been revealed for the first time
      in B. mori. The innervating neurons supply both Bommo-FMRF related peptide (BRFa)
      and orcokinin to maintain low levels of ecdysteroids during the feeding stage.
      These complex regulatory mechanisms - involving tropic and static factors,
      peripheral neurosecretory cells as well as the central neuroendocrine system, and
      neural regulation in addition to circulating factors collaborate to regulate
      ecdysteroidogenesis. Thus, together they create the finely tuned fluctuations in
      ecdysteroid titers needed in the hemolymph during insect development.

PMID- 22645517
TI  - Cardiometabolic complications after androgen deprivation therapy in a man with
      prostate cancer: effects of 3 years intermittent testosterone supplementation.
AB  - Androgen deprivation therapy (ADT) for prostate carcinoma (PCa) may cause
      cardiometabolic complications unless intermittent androgen blockade (IAB) is
      instituted. An 80-year-old caucasian man was diagnosed intermediate grade
      (Gleason 4 + 3) PCa and was treated with continuous ADT with triptorelin plus
      bicalutamide. After 6 months of treatment, he experienced an acute myocardial
      infarction and 1 month after hospitalization he came to our outpatient clinic for
      fatigue, weight gain, and hyperglycemia. Due to iatrogenic hypogonadism, we
      decided to proceed with IAB, but after 3 months ADT withdrawal his serum
      testosterone (T) was still 0.5 ng/mL. Due to very low concomitant PSA levels (0.1
      ng/mL) he was then proposed intermittent T-gel supplementation (Tostrex((r)))
      which was initiated according to the following scheme: 6 months on and 3 months
      off. T-gel dose was titrated tri-weekly in order to achieve T plasma levels below
      3.49 ng/mL. After 6 months on, his serum T raised to a mean value of about 2.0
      ng/mL without increments in PSA. After overall 12 months on, his serum T peaked
      to a mean value of 3.0 ng/mL while a delay in PSA rise was seen after 24 months
      (0.6 ng/mL) but remained stable until the last observation carried forward
      (LOCF), at 45 months. No clinical and biochemical PCa progression were observed
      at LOCF. Reversion of iatrogenic metabolic syndrome started after 6 months of T
      supplementation without using any add-on treatment. This case provides support
      that once regression of PCa growth is attained, T supplementation may be
      administered in well differentiated PCa, especially if IAB is not successful in
      reverting iatrogenic hypogonadism and its associated cardiac and metabolic
      complications.

PMID- 22645518
TI  - Differential roles of GnRH-I and GnRH-ii neurons in the control of the primate
      reproductive axis.
AB  - In vertebrates, gonadotropin-releasing hormone (GnRH) represents the primary
      neuroendocrine link between the brain and the reproductive axis, and in some
      species up to three different forms of GnRH have been detected. Until recently,
      it had been assumed that humans and non-human primates only express one form
      (GnRH-I), but it is now clear they also express a second form (GnRH-II). GnRH-II,
      like GnRH-I, is highly effective at stimulating gonadotropin release, both in
      vitro and in vivo, but the neurons that produce GnRH-II are completely distinct
      from those producing GnRH-I. Moreover, GnRH-II and GnRH-I producing neurons
      respond very differently to estradiol; specifically, estradiol stimulates GnRH-II
      gene expression in the former and inhibit GnRH-I gene expression in the latter.
      Consequently, the negative feedback action of estradiol may be mediated
      exclusively by the subpopulation of GnRH neurons that express GnRH-I, while the
      positive feedback action may be mediated exclusively by the subpopulation that
      expresses GnRH-II. Taken together, these findings raise the possibility that two
      completely different GnRH neuronal systems participate in the control of primate
      reproductive physiology. The primary role of GnRH-I neurons is likely to be
      focused on the maintenance and modulation of tonic pulsatile LH release, whereas
      the primary role of GnRH-II neurons is likely to be focused on the generation of
      the preovulatory LH surge. This functional segregation of the primate
      neuroendocrine reproductive axis lends itself for novel targeted approaches to
      fertility control and for treatment of human reproductive disorders.

PMID- 22645519
TI  - Variability in the heritability of body mass index: a systematic review and meta
      regression.
AB  - Evidence for a major role of genetic factors in the determination of body mass
      index (BMI) comes from studies of related individuals. Despite consistent
      evidence for a heritable component of BMI, estimates of BMI heritability vary
      widely between studies and the reasons for this remain unclear. While some
      variation is natural due to differences between populations and settings, study
      design factors may also explain some of the heterogeneity. We performed a
      systematic review that identified 88 independent estimates of BMI heritability
      from twin studies (total 140,525 twins) and 27 estimates from family studies
      (42,968 family members). BMI heritability estimates from twin studies ranged from
      0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher
      than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles:
      0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI
      heritability estimates were 0.07 (P = 0.001) higher in children than in adults;
      estimates increased with mean age among childhood studies (+0.012/year, P =
      0.002), but decreased with mean age in adult studies (-0.002/year, P = 0.002).
      Heritability estimates derived from AE twin models (which assume no contribution
      of shared environment) were 0.12 higher than those from ACE models (P < 0.001),
      whilst lower estimates were associated with self reported versus DNA-based
      determination of zygosity (-0.04, P = 0.02), and with self reported versus
      measured BMI (-0.05, P = 0.03). Although the observed differences in heritability
      according to aspects of study design are relatively small, together, the above
      factors explained 47% of the heterogeneity in estimates of BMI heritability from
      twin studies. In summary, while some variation in BMI heritability is expected
      due to population-level differences, study design factors explained nearly half
      the heterogeneity reported in twin studies. The genetic contribution to BMI
      appears to vary with age and may have a greater influence during childhood than
      adult life.

PMID- 22645520
TI  - Role of the wnt pathway in thyroid cancer.
AB  - Aberrant activation of Wnt signaling is involved in the development of several
      epithelial tumors. Wnt signaling includes two major types of pathways: (i) the
      canonical or Wnt/beta-catenin pathway; and (ii) the non-canonical pathways, which
      do not involve beta-catenin stabilization. Among these pathways, the Wnt/beta
      catenin pathway has received most attention during the past years for its
      critical role in cancer. A number of publications emphasize the role of the
      Wnt/beta-catenin pathway in thyroid cancer. This pathway plays a crucial role in
      development and epithelial renewal, and components such as beta-catenin and Axin
      are often mutated in thyroid cancer. Although it is accepted that altered Wnt
      signaling is a late event in thyroid cell transformation that affects anaplastic
      thyroid tumors, recent data suggest that it is also altered in papillary thyroid
      carcinoma (PTC) with RET/PTC mutations. Therefore, the purpose of this review is
      to summarize the main relevant data of Wnt signaling in thyroid cancer, with
      special emphasis on the Wnt/beta-catenin pathway.

PMID- 22645522
TI  - Identification of Smad Response Elements in the Promoter of Goldfish FSHbeta Gene
      and Evidence for Their Mediation of Activin and GnRH Stimulation of FSHbeta
      Expression.
AB  - As an essential hormone regulating gonads in vertebrates, the biosynthesis and
      secretion of follicle-stimulating hormone (FSH) is controlled by a variety of
      endocrine and paracrine factors in both mammalian and non-mammalian vertebrates.
      Activin was initially discovered in the ovary for its specific stimulation of FSH
      secretion by the pituitary cells. Our earlier studies in fish have shown that
      activin stimulates FSHbeta but suppresses LHbeta expression in both the goldfish
      and zebrafish. Further experiments showed that the regulation of FSHbeta in fish
      occurred at the promoter level involving Smads, in particular Smad3. To further
      understand the mechanisms by which activin/Smad regulates FSHbeta transcription,
      the present study was undertaken to analyze the promoter of goldfish FSHbeta gene
      (fshb) with the aim to identify potential cis-regulatory elements responsible for
      activin/Smad stimulation. Both serial deletion and site-directed mutagenesis were
      used, and the promoter activity was tested in the LbetaT-2 cells, a murine
      gonadotroph cell line. The reporter constructs of goldfish FSHbeta promoter-SEAP
      (secreted alkaline phosphatase) were co-transfected with an expression plasmid
      for Smads (2 or 3) followed by measurement of SEAP activity in the medium. Two
      putative Smad responsive elements were identified in the promoter at distal and
      proximal regions, respectively. The distal site contained a consensus Smad
      binding element (AGAC, -1675/-1672) whereas the proximal site (GACCTTGA, -212/
      205) was identical to an SF-1 binding site reported in humans, which was preceded
      by a sequence (AACACTGA) highly conserved between fish and mammals. The proximal
      site also seemed to be involved in mediating stimulation of FSHbeta expression by
      gonadotropin-releasing hormone and its potential interaction with activin. In
      conclusion, we have identified two potential cis-regulatory elements in the
      promoter of goldfish FSHbeta that are responsible for activin-induced expression
      of the gene. Since activin stimulation of FSHbeta expression is functionally
      conserved in fish and mammals, our findings contribute to the understanding of
      the fundamental mechanisms of this regulation across vertebrates.

PMID- 22645523
TI  - Nodal promotes glioblastoma cell growth.
AB  - Nodal is a member of the transforming growth factor-beta (TGF-beta) superfamily
      that plays critical roles during embryogenesis. Recent studies in ovarian,
      breast, prostate, and skin cancer cells suggest that Nodal also regulates cell
      proliferation, apoptosis, and invasion in cancer cells. However, it appears to
      exert both tumor-suppressing and tumor-promoting effects, depending on the cell
      type. To further understand the role of Nodal in tumorigenesis, we examined the
      effect of Nodal in glioblastoma cell growth and spheroid formation using U87 cell
      line. Treatment of U87 with recombinant Nodal significantly increased U87 cell
      growth. In U87 cells stably transfected with the plasmid encoding Nodal, Smad2
      phosphorylation was strongly induced and cell growth was significantly enhanced.
      Overexpression of Nodal also resulted in tight spheroid formation. On the other
      hand, the cells stably transfected with Nodal siRNA formed loose spheroids. Nodal
      is known to signal through activin receptor-like kinase 4 (ALK4) and ALK7 and the
      Smad2/3 pathway. To determine which receptor and Smad mediate the growth
      promoting effect of Nodal, we transfected siRNAs targeting ALK4, ALK7, Smad2, or
      Smad3 into Nodal-overexpressing cells and observed that cell growth was
      significantly inhibited by ALK4, ALK7, and Smad3 siRNAs. Taken together, these
      findings suggest that Nodal may have tumor-promoting effects on glioblastoma
      cells and these effects are mediated by ALK4, ALK7, and Smad3.

PMID- 22645524
TI  - Grand opportunities in plant science to address the grand challenges facing the
      planet.

PMID- 22645525
TI  - Dose-sensitivity, conserved non-coding sequences, and duplicate gene retention
      through multiple tetraploidies in the grasses.
AB  - Whole genome duplications, or tetraploidies, are an important source of increased
      gene content. Following whole genome duplication, duplicate copies of many genes
      are lost from the genome. This loss of genes is biased both in the classes of
      genes deleted and the subgenome from which they are lost. Many or all classes are
      genes preferentially retained as duplicate copies are engaged in dose sensitive
      protein-protein interactions, such that deletion of any one duplicate upsets the
      status quo of subunit concentrations, and presumably lowers fitness as a result.
      Transcription factors are also preferentially retained following every whole
      genome duplications studied. This has been explained as a consequence of protein
      protein interactions, just as for other highly retained classes of genes. We show
      that the quantity of conserved noncoding sequences (CNSs) associated with genes
      predicts the likelihood of their retention as duplicate pairs following whole
      genome duplication. As many CNSs likely represent binding sites for
      transcriptional regulators, we propose that the likelihood of gene retention
      following tetraploidy may also be influenced by dose-sensitive protein-DNA
      interactions between the regulatory regions of CNS-rich genes - nicknamed bigfoot
      genes - and the proteins that bind to them. Using grass genomes, we show that
      differential loss of CNSs from one member of a pair following the pre-grass
      tetraploidy reduces its chance of retention in the subsequent maize lineage
      tetraploidy.

PMID- 22645521
TI  - The Changes They are A-Timed: Metabolism, Endogenous Clocks, and the Timing of
      Puberty.
AB  - Childhood obesity has increased dramatically over the last several decades,
      particularly in industrialized countries, often accompanied by acceleration of
      pubertal progression and associated reproductive abnormalities (Biro et al.,
      2006; Rosenfield et al., 2009). The timing of pubertal initiation and progression
      in mammals is likely influenced by nutritional and metabolic state, leading to
      the hypothesis that deviations from normal metabolic rate, such as those seen in
      obesity, may contribute to observed alterations in the rate of pubertal
      progression. While several recent reviews have addressed the effects of metabolic
      disorders on reproductive function in general, this review will explore previous
      and current models of pubertal timing, outlining a potential role of endogenous
      timing mechanisms such as cellular circadian clocks in the initiation of puberty,
      and how these clocks might be altered by metabolic factors. Additionally, we will
      examine recently elucidated neuroendocrine regulators of pubertal progression
      such as kisspeptin, explore models detailing how the mammalian reproductive axis
      is silenced during the juvenile period and reactivated at appropriate
      developmental times, and emphasize how metabolic dysfunction such as childhood
      obesity may alter timing cues that advance or delay pubertal progression,
      resulting in diminished reproductive capacity.

PMID- 22645526
TI  - Phenotype Uniformity in Combined-Stress Environments has a Different Genetic
      Architecture than in Single-Stress Treatments.
AB  - For crop production it is desirable for the mapping between genotype and
      phenotype to be consistent, such that an optimized genotype produces uniform sets
      of individual plants. Uniformity is strongly selected in breeding programs,
      usually automatically, as harvest equipment eliminates severely non-uniform
      individuals. Uniformity is genetically controlled, is known to be increased by
      interplant competition, and is predicted to increase upon abiotic stress. We
      mapped maize loci controlling genotype by environment interaction in plant height
      uniformity. These loci are different than the loci controlling mean plant height.
      Uniformity decreases upon combining two abiotic stresses, with alleles conferring
      greater uniformity in a single stress showing little improvement in a combined
      stress treatment. The maize B73 and Mo17 inbreds do not provide segregating
      alleles for improvement in plant height uniformity, suggesting that the genetic
      network specifying plant height has a past history of selection for robustness.

PMID- 22645528
TI  - Hot and retro meet Arabidopsis.

PMID- 22645527
TI  - PD Trafficking of Potato Leaf Roll Virus Movement Protein in Arabidopsis Depends
      on Site-specific Protein Phosphorylation.
AB  - Many plant viruses encode for specialized movement proteins (MP) to facilitate
      passage of viral material to and through plasmodesmata (PD). To analyze
      intracellular trafficking of potato leaf roll virus (PLRV) movement protein
      (MP17) we performed GFP fusion experiments with distinct deletion variants of
      MP17. These studies revealed that the C-terminus of MP17 is essential but not
      sufficient for PD targeting. Interestingly, fusion of GFP to three C-terminal
      MP17 deletion variants resulted in the accumulation of GFP in chloroplasts. This
      indicates that MP17 harbors hidden plastid targeting sequences. Previous studies
      showed that posttranslational protein phosphorylation influences PD targeting of
      MP and virus spread. Analysis of MP17-derived phospho-peptides by mass
      spectrometry revealed four phosphorylated serine residues (S71, S79, S137, and
      S140). Site-directed mutagenesis of S71/S79 and S137/S140 showed that the C
      terminal serine residues S137/S140 are dispensable for PD targeting. However,
      exchange of S71/S79 to A71/A79 abolished PD targeting of the mutated MP17
      protein. To mimic phosphorylation of S71/S79 both amino acids were substituted by
      aspartic acid. The resulting D71/D79 variant of MP17 was efficiently targeted to
      PD. Further deletion analysis showed that PD targeting of MP17 is dependent on
      the C-terminus, phosphorylation of S71 and/or S79 and a N-terminal domain.

PMID- 22645529
TI  - The MADS Symphonies of Transcriptional Regulation.

PMID- 22645530
TI  - Adventures with cyanobacteria: a personal perspective.
AB  - Cyanobacteria, or the blue-green algae as they used to be called until 1974, are
      the oldest oxygenic photosynthesizers. We summarize here adventures with them
      since the early 1960s. This includes studies on light absorption by
      cyanobacteria, excitation energy transfer at room temperature down to liquid
      helium temperature, fluorescence (kinetics as well as spectra) and its
      relationship to photosynthesis, and afterglow (or thermoluminescence) from them.
      Further, we summarize experiments on their two-light reaction - two-pigment
      system, as well as the unique role of bicarbonate (hydrogen carbonate) on the
      electron-acceptor side of their photosystem II, PSII. This review, in addition,
      includes a discussion on the regulation of changes in phycobilins (mostly in
      PSII) and chlorophyll a (Chl a; mostly in photosystem I, PSI) under oscillating
      light, on the relationship of the slow fluorescence increase (the so-called S to
      M rise, especially in the presence of diuron) in minute time scale with the so
      called state-changes, and on the possibility of limited oxygen evolution in
      mixotrophic PSI (minus) mutants, up to 30 min, in the presence of glucose. We end
      this review with a brief discussion on the position of cyanobacteria in the
      evolution of photosynthetic systems.

PMID- 22645531
TI  - The iPlant Collaborative: Cyberinfrastructure for Plant Biology.
AB  - The iPlant Collaborative (iPlant) is a United States National Science Foundation
      (NSF) funded project that aims to create an innovative, comprehensive, and
      foundational cyberinfrastructure in support of plant biology research (PSCIC,
      2006). iPlant is developing cyberinfrastructure that uniquely enables scientists
      throughout the diverse fields that comprise plant biology to address Grand
      Challenges in new ways, to stimulate and facilitate cross-disciplinary research,
      to promote biology and computer science research interactions, and to train the
      next generation of scientists on the use of cyberinfrastructure in research and
      education. Meeting humanity's projected demands for agricultural and forest
      products and the expectation that natural ecosystems be managed sustainably will
      require synergies from the application of information technologies. The iPlant
      cyberinfrastructure design is based on an unprecedented period of research
      community input, and leverages developments in high-performance computing, data
      storage, and cyberinfrastructure for the physical sciences. iPlant is an open
      source project with application programming interfaces that allow the community
      to extend the infrastructure to meet its needs. iPlant is sponsoring community
      driven workshops addressing specific scientific questions via analysis tool
      integration and hypothesis testing. These workshops teach researchers how to add
      bioinformatics tools and/or datasets into the iPlant cyberinfrastructure enabling
      plant scientists to perform complex analyses on large datasets without the need
      to master the command-line or high-performance computational services.

PMID- 22645532
TI  - Calcium-dependent protein kinases from Arabidopsis show substrate specificity
      differences in an analysis of 103 substrates.
AB  - The identification of substrates represents a critical challenge for
      understanding any protein kinase-based signal transduction pathway. In
      Arabidopsis, there are more than 1000 different protein kinases, 34 of which
      belong to a family of Ca(2+)-dependent protein kinases (CPKs). While CPKs are
      implicated in regulating diverse aspects of plant biology, from ion transport to
      transcription, relatively little is known about isoform-specific differences in
      substrate specificity, or the number of phosphorylation targets. Here, in vitro
      kinase assays were used to compare phosphorylation targets of four CPKs from
      Arabidopsis (CPK1, 10, 16, and 34). Significant differences in substrate
      specificity for each kinase were revealed by assays using 103 different
      substrates. For example CPK16 phosphorylated Serine 109 in a peptide from the
      stress-regulated protein, Di19-2 with K(M) ~70 MUM, but this site was not
      phosphorylated significantly by CPKs 1, 10, or 34. In contrast, CPKs 1, 10, and
      34 phosphorylated 93 other peptide substrates not recognized by CPK16. Examples
      of substrate specificity differences among all four CPKs were verified by kinetic
      analyses. To test the correlation between in vivo phosphorylation events and in
      vitro kinase activities, assays were performed with 274 synthetic peptides that
      contained phosphorylation sites previously mapped in proteins isolated from
      plants (in vivo-mapped sites). Of these, 74 (27%) were found to be phosphorylated
      by at least one of the four CPKs tested. This 27% success rate validates a robust
      strategy for linking the activities of specific kinases, such as CPKs, to the
      thousands of in planta phosphorylation sites that are being uncovered by emerging
      technologies.

PMID- 22645533
TI  - Flux-balance modeling of plant metabolism.
AB  - Flux-balance modeling of plant metabolic networks provides an important
      complement to (13)C-based metabolic flux analysis. Flux-balance modeling is a
      constraints-based approach in which steady-state fluxes in a metabolic network
      are predicted by using optimization algorithms within an experimentally bounded
      solution space. In the last 2 years several flux-balance models of plant
      metabolism have been published including genome-scale models of Arabidopsis
      metabolism. In this review we consider what has been learnt from these models. In
      addition, we consider the limitations of flux-balance modeling and identify the
      main challenges to generating improved and more detailed models of plant
      metabolism at tissue- and cell-specific scales. Finally we discuss the types of
      question that flux-balance modeling is well suited to address and its potential
      role in metabolic engineering and crop improvement.

PMID- 22645534
TI  - Common Motifs in the Response of Cereal Primary Metabolism to Fungal Pathogens
      are not Based on Similar Transcriptional Reprogramming.
AB  - During compatible interactions with their host plants, biotrophic plant-pathogens
      subvert host metabolism to ensure the sustained provision of nutrient assimilates
      by the colonized host cells. To investigate, whether common motifs can be
      revealed in the response of primary carbon and nitrogen metabolism toward
      colonization with biotrophic fungi in cereal leaves, we have conducted a combined
      metabolome and transcriptome study of three quite divergent pathosystems, the
      barley powdery mildew fungus (Blumeria graminis f.sp. hordei), the corn smut
      fungus Ustilago maydis, and the maize anthracnose fungus Colletotrichum
      graminicola, the latter being a hemibiotroph that only exhibits an initial
      biotrophic phase during its establishment. Based on the analysis of 42 water
      soluble metabolites, we were able to separate early biotrophic from late
      biotrophic interactions by hierarchical cluster analysis and principal component
      analysis, irrespective of the plant host. Interestingly, the corresponding
      transcriptome dataset could not discriminate between these stages of biotrophy,
      irrespective, of whether transcript data for genes of central metabolism or the
      entire transcriptome dataset was used. Strong differences in the transcriptional
      regulation of photosynthesis, glycolysis, the TCA cycle, lipid biosynthesis, and
      cell wall metabolism were observed between the pathosystems. However, increased
      contents of Gln, Asn, and glucose as well as diminished contents of PEP and 3-PGA
      were common to early post-penetration stages of all interactions. On the
      transcriptional level, genes of the TCA cycle, nucleotide energy metabolism and
      amino acid biosynthesis exhibited consistent trends among the compared biotrophic
      interactions, identifying the requirement for metabolic energy and the
      rearrangement of amino acid pools as common transcriptional motifs during early
      biotrophy. Both metabolome and transcript data were employed to generate models
      of leaf primary metabolism during early biotrophy for the three investigated
      interactions.

PMID- 22645535
TI  - Mass spectra-based framework for automated structural elucidation of metabolome
      data to explore phytochemical diversity.
AB  - A novel framework for automated elucidation of metabolite structures in liquid
      chromatography-mass spectrometer metabolome data was constructed by integrating
      databases. High-resolution tandem mass spectra data automatically acquired from
      each metabolite signal were used for database searches. Three distinct databases,
      KNApSAcK, ReSpect, and the PRIMe standard compound database, were employed for
      the structural elucidation. The outputs were retrieved using the CAS metabolite
      identifier for identification and putative annotation. A simple metabolite
      ontology system was also introduced to attain putative characterization of the
      metabolite signals. The automated method was applied for the metabolome data sets
      obtained from the rosette leaves of 20 Arabidopsis accessions. Phenotypic
      variations in novel Arabidopsis metabolites among these accessions could be
      investigated using this method.

PMID- 22645536
TI  - Plant glutathione biosynthesis: diversity in biochemical regulation and reaction
      products.
AB  - In plants, exposure to temperature extremes, heavy metal-contaminated soils,
      drought, air pollutants, and pathogens results in the generation of reactive
      oxygen species that alter the intracellular redox environment, which in turn
      influences signaling pathways and cell fate. As part of their response to these
      stresses, plants produce glutathione. Glutathione acts as an anti-oxidant by
      quenching reactive oxygen species, and is involved in the ascorbate-glutathione
      cycle that eliminates damaging peroxides. Plants also use glutathione for the
      detoxification of xenobiotics, herbicides, air pollutants (sulfur dioxide and
      ozone), and toxic heavy metals. Two enzymes catalyze glutathione synthesis:
      glutamate-cysteine ligase, and glutathione synthetase. Glutathione is a
      ubiquitous protective compound in plants, but the structural and functional
      details of the proteins that synthesize it, as well as the potential biochemical
      mechanisms of their regulation, have only begun to be explored. As discussed
      here, the core reactions of glutathione synthesis are conserved across various
      organisms, but plants have diversified both the regulatory mechanisms that
      control its synthesis and the range of products derived from this pathway.
      Understanding the molecular basis of glutathione biosynthesis and its regulation
      will expand our knowledge of this component in the plant stress response network.

PMID- 22645537
TI  - Rewiring of the Jasmonate Signaling Pathway in Arabidopsis during Insect
      Herbivory.
AB  - Plant defenses against insect herbivores and necrotrophic pathogens are
      differentially regulated by different branches of the jasmonic acid (JA)
      signaling pathway. In Arabidopsis, the basic helix-loop-helix leucine zipper
      transcription factor (TF) MYC2 and the APETALA2/ETHYLENE RESPONSE FACTOR
      (AP2/ERF) domain TF ORA59 antagonistically control these distinct branches of the
      JA pathway. Feeding by larvae of the specialist insect herbivore Pieris rapae
      activated MYC2 transcription and stimulated expression of the MYC2-branch marker
      gene VSP2, while it suppressed transcription of ORA59 and the ERF-branch marker
      gene PDF1.2. Mutant jin1 and jar1-1 plants, which are impaired in the MYC2-branch
      of the JA pathway, displayed a strongly enhanced expression of both ORA59 and
      PDF1.2 upon herbivory, indicating that in wild-type plants the MYC2-branch is
      prioritized over the ERF-branch during insect feeding. Weight gain of P. rapae
      larvae in a no-choice setup was not significantly affected, but in a two-choice
      setup the larvae consistently preferred jin1 and jar1-1 plants, in which the ERF
      branch was activated, over wild-type Col-0 plants, in which the MYC2-branch was
      induced. In MYC2- and ORA59-impaired jin1-1/RNAi-ORA59 plants this preference was
      lost, while in ORA59-overexpressing 35S:ORA59 plants it was gained, suggesting
      that the herbivores were stimulated to feed from plants that expressed the ERF
      branch rather than that they were deterred by plants that expressed the MYC2
      branch. The feeding preference of the P. rapae larvae could not be linked to
      changes in glucosinolate levels. Interestingly, application of larval oral
      secretion into wounded leaf tissue stimulated the ERF-branch of the JA pathway,
      suggesting that compounds in the oral secretion have the potential to manipulate
      the plant response toward the caterpillar-preferred ERF-regulated branch of the
      JA response. Our results suggest that by activating the MYC2-branch of the JA
      pathway, plants prevent stimulation of the ERF-branch by the herbivore, thereby
      becoming less attractive to the attacker.

PMID- 22645539
TI  - Plant Breeding: A Success Story to be Continued Thanks to the Advances in
      Genomics.

PMID- 22645538
TI  - The metabolite transporters of the plastid envelope: an update.
AB  - The engulfment of a photoautotrophic cyanobacterium by a primitive mitochondria
      bearing eukaryote traces back to more than 1.2 billion years ago. This single
      endosymbiotic event not only provided the early petroalgae with the metabolic
      capacity to perform oxygenic photosynthesis, but also introduced a plethora of
      other metabolic routes ranging from fatty acids and amino acids biosynthesis,
      nitrogen and sulfur assimilation to secondary compounds synthesis. This
      implicated the integration and coordination of the newly acquired metabolic
      entity with the host metabolism. The interface between the host cytosol and the
      plastidic stroma became of crucial importance in sorting precursors and products
      between the plastid and other cellular compartments. The plastid envelope
      membranes fulfill different tasks: they perform important metabolic functions, as
      they are involved in the synthesis of carotenoids, chlorophylls, and
      galactolipids. In addition, since most genes of cyanobacterial origin have been
      transferred to the nucleus, plastidial proteins encoded by nuclear genes are post
      translationally transported across the envelopes through the TIC-TOC import
      machinery. Most importantly, chloroplasts supply the photoautotrophic cell with
      photosynthates in form of reduced carbon. The innermost bilayer of the plastidic
      envelope represents the permeability barrier for the metabolites involved in the
      carbon cycle and is literally stuffed with transporter proteins facilitating
      their transfer. The intracellular metabolite transporters consist of polytopic
      proteins containing membrane spans usually in the number of four or more alpha
      helices. Phylogenetic analyses revealed that connecting the plastid with the host
      metabolism was mainly a process driven by the host cell. In Arabidopsis, 58% of
      the metabolite transporters are of host origin, whereas only 12% are attributable
      to the cyanobacterial endosymbiont. This review focuses on the metabolite
      transporters of the inner envelope membrane of plastids, in particular the
      electrochemical potential-driven class of transporters. Recent advances in
      elucidating the plastidial complement of metabolite transporters are provided,
      with an update on phylogenetic relationship of selected proteins.

PMID- 22645541
TI  - Analysis of the compartmentalized metabolome - a validation of the non-aqueous
      fractionation technique.
AB  - With the development of high-throughput metabolic technologies, a plethora of
      primary and secondary compounds have been detected in the plant cell. However,
      there are still major gaps in our understanding of the plant metabolome. This is
      especially true with regards to the compartmental localization of these
      identified metabolites. Non-aqueous fractionation (NAF) is a powerful technique
      for the determination of subcellular metabolite distributions in eukaryotic
      cells, and it has become the method of choice to analyze the distribution of a
      large number of metabolites concurrently. However, the NAF technique produces a
      continuous gradient of metabolite distributions, not discrete assignments.
      Resolution of these distributions requires computational analyses based on marker
      molecules to resolve compartmental localizations. In this article we focus on
      expanding the computational analysis of data derived from NAF. Along with an
      experimental workflow, we describe the critical steps in NAF experiments and how
      computational approaches can aid in assessing the quality and robustness of the
      derived data. For this, we have developed and provide a new version (v1.2) of the
      BestFit command line tool for calculation and evaluation of subcellular
      metabolite distributions. Furthermore, using both simulated and experimental data
      we show the influence on estimated subcellular distributions by modulating
      important parameters, such as the number of fractions taken or which marker
      molecule is selected. Finally, we discuss caveats and benefits of NAF analysis in
      the context of the compartmentalized metabolome.

PMID- 22645542
TI  - Disruption of a Novel NADH-Glutamate Synthase2 Gene Caused Marked Reduction in
      Spikelet Number of Rice.
AB  - Inorganic ammonium ions are assimilated by a coupled reaction of glutamine
      synthetase and glutamate synthase (GOGAT). In rice, three genes encoding either
      ferredoxin (Fd)-GOGAT, NADH-GOGAT1, or NADH-GOGAT2, have been identified. OsNADH
      GOGAT2, a newly identified gene, was expressed mainly in fully expanded leaf
      blades and leaf sheaths. Although the distinct expression profile to OsNADH
      GOGAT1, which is mainly detected in root tips, developing leaf blades, and
      grains, was shown in our previous studies, physiological role of NADH-GOGAT2 is
      not yet known. Here, we isolated retrotransposon mediated-knockout mutants
      lacking OsNADH-GOGAT2. In rice grown under paddy field conditions, disruption of
      the OsNADH-GOGAT2 gene caused a remarkable decrease in spikelet number per
      panicle associated with a reductions in yield and whole plant biomass, when
      compared with wild-type (WT) plants. The total nitrogen contents in the senescing
      leaf blade of the mutants were approximately a half of the WT plants. Expression
      of this gene was mainly detected in phloem companion cells and phloem parenchyma
      cells associated with large vascular bundles in fully expanded leaf blades, when
      the promoter region fused with a beta-glucuronidase gene was introduced into the
      WT rice. These results suggest that the NADH-GOGAT2 is important in the process
      of glutamine generation in senescing leaves for the remobilization of leaf
      nitrogen through phloem to the panicle during natural senescence. These results
      also indicate that other GOGATs, i.e., NADH-GOGAT1 and ferredoxin-GOGAT are not
      able to compensate the function of NADH-GOGAT2.

PMID- 22645540
TI  - The stem cell state in plant development and in response to stress.
AB  - Stem cells are commonly defined by their developmental capabilities, namely, self
      renewal and multitype differentiation, yet the biology of stem cells and their
      inherent features both in plants and animals are only beginning to be elucidated.
      In this review article we highlight the stem cell state in plants with reference
      to animals and the plastic nature of plant somatic cells often referred to as
      totipotency as well as the essence of cellular dedifferentiation. Based on recent
      published data, we illustrate the picture of stem cells with emphasis on their
      open chromatin conformation. We discuss the process of dedifferentiation and
      highlight its transient nature, its distinction from re-entry into the cell cycle
      and its activation following exposure to stress. We also discuss the potential
      hazard that can be brought about by stress-induced dedifferentiation and its
      major impact on the genome, which can undergo stochastic, abnormal reorganization
      leading to genetic variation by means of DNA transposition and/or DNA
      recombination.

PMID- 22645543
TI  - The use of natural genetic diversity in the understanding of metabolic
      organization and regulation.
AB  - The study of metabolic regulation has traditionally focused on analysis of
      specific enzymes, emphasizing kinetic properties, and the influence of protein
      interactions and post-translational modifications. More recently, reverse genetic
      approaches permit researchers to directly determine the effects of a deficiency
      or a surplus of a given enzyme on the biochemistry and physiology of a plant.
      Furthermore, in many model species, gene expression atlases that give important
      spatial information concerning the quantitative expression level of metabolism
      associated genes are being produced. In parallel, "top-down" approaches to
      understand metabolic regulation have recently been instigated whereby broad
      genetic diversity is screened for metabolic traits and the genetic basis of this
      diversity is defined thereafter. In this article we will review recent examples
      of this latter approach both in the model species Arabidopsis thaliana and the
      crop species tomato (Solanum lycopersicum). In addition to highlighting examples
      in which this genetic diversity approach has proven promising, we will discuss
      the challenges associated with this approach and provide a perspective for its
      future utility.

PMID- 22645544
TI  - Geometric constraints and the anatomical interpretation of twisted plant organ
      phenotypes.
AB  - The study of plant mutants with twisting growth in axial organs, which normally
      grow straight in the wild-type, is expected to improve our understanding of the
      interplay among microtubules, cellulose biosynthesis, cell wall structure, and
      organ biomechanics that control organ growth and morphogenesis. However,
      geometric constraints based on symplastic growth and the consequences of these
      geometric constraints concerning interpretations of twisted-organ phenotypes are
      currently underestimated. Symplastic growth, a fundamental concept in plant
      developmental biology, is characterized by coordinated growth of adjacent cells
      based on their connectivity through cell walls. This growth behavior implies that
      in twisting axial organs, all cell files rotate in phase around the organ axis,
      as has been illustrated for the Arabidopsisspr1 and twd1 mutants in this work.
      Evaluating the geometry of such organs, we demonstrate that a radial gradient in
      cell elongation and changes in cellular growth anisotropy must occur in twisting
      organs out of geometric necessity alone. In-phase rotation of the different cell
      layers results in a decrease of length and angle toward organ axis from the outer
      cell layers inward. Additionally, the circumference of each cell layer increases
      in twisting organs, which requires compensation through radial expansion or an
      adjustment of cell number. Therefore, differential cell elongation and growth
      anisotropy cannot serve as arguments for or against specific hypotheses regarding
      the molecular cause of twisting growth. We suggest instead, that based on
      mathematical modeling, geometric constraints in twisting organs are indispensable
      for the explanation of the causal connection of molecular and biomechanical
      processes in twisting as well as normal organs.

PMID- 22645545
TI  - Protein-Protein and Protein-DNA Dosage Balance and Differential Paralog
      Transcription Factor Retention in Polyploids.

PMID- 22645546
TI  - Metabolite profile changes in xylem sap and leaf extracts of strategy I plants in
      response to iron deficiency and resupply.
AB  - The metabolite profile changes induced by Fe deficiency in leaves and xylem sap
      of several Strategy I plant species have been characterized. We have confirmed
      that Fe deficiency causes consistent changes both in the xylem sap and leaf
      metabolite profiles. The main changes in the xylem sap metabolite profile in
      response to Fe deficiency include consistent decreases in amino acids, N-related
      metabolites and carbohydrates, and increases in TCA cycle metabolites. In tomato,
      Fe resupply causes a transitory flush of xylem sap carboxylates, but within 1 day
      the metabolite profile of the xylem sap from Fe-deficient plants becomes similar
      to that of Fe-sufficient controls. The main changes in the metabolite profile of
      leaf extracts in response to Fe deficiency include consistent increases in amino
      acids and N-related metabolites, carbohydrates and TCA cycle metabolites. In
      leaves, selected pairs of amino acids and TCA cycle metabolites show high
      correlations, with the sign depending of the Fe status. These data suggest that
      in low photosynthesis, C-starved Fe-deficient plants anaplerotic reactions
      involving amino acids can be crucial for short-term survival.

PMID- 22645547
TI  - Molecular screening tools to study Arabidopsis transcription factors.
AB  - In the model plant Arabidopsis thaliana, more than 2000 genes are estimated to
      encode transcription factors (TFs), which clearly emphasizes the importance of
      transcriptional control. Although genomic approaches have generated large TF open
      reading frame (ORF) collections, only a limited number of these genes is
      functionally characterized, yet. This review evaluates strategies and methods to
      identify TF functions. In particular, we focus on two recently developed TF
      screening platforms, which make use of publically available GATEWAY((r))
      compatible ORF collections. (1) The Arabidopsis thalianaTF ORF over-Expression
      (AtTORF-Ex) library provides pooled collections of transgenic lines over
      expressing HA-tagged TF genes, which are suited for screening approaches to
      define TF functions in stress defense and development. (2) A high-throughput
      microtiter plate based protoplast transactivation (PTA) system has been
      established to screen for TFs which are regulating a given promoter:Luciferase
      construct in planta.

PMID- 22645548
TI  - Analysis of Organelle Targeting by DIL Domains of the Arabidopsis Myosin XI
      Family.
AB  - The Arabidopsis thaliana genome encodes 13 myosin XI motor proteins. Previous
      insertional mutant analysis has implicated substantial redundancy of function of
      plant myosin XIs in transport of intracellular organelles. Considerable
      information is available about the interaction of cargo with the myosin XI
      homologous yeast myosin V protein myo2p. We identified a region in each of 12
      myosin XI sequences that correspond to the yeast myo2p secretory-vesicle binding
      domain (the "DIL" domain). Structural modeling of the myosin DIL domain region of
      plant myosin XIs revealed significant similarity to the yeast myo2p and myo4p DIL
      domains. Transient expression of YFP fusions with the Arabidopsis myosin XI DIL
      domain resulted in fluorescent labeling of a variety of organelles, including the
      endoplasmic reticulum, peroxisomes, Golgi, and nuclear envelope. With the
      exception of the YFP::MYA1 DIL fusion, expression of the DIL-YFP fusions resulted
      in loss of motility of labeled organelles, consistent with a dominant-negative
      effect. Certain fusions resulted in localization to the cytoplasm, plasma
      membrane, or to unidentified vesicles. The same YFP-domain fusion sometimes
      labeled more than one organelle. Expression of a YFP fusion to a yeast myo2p DIL
      domain resulted in labeling of plant peroxisomes. Fusions with some of the myosin
      XI domains resulted in labeling of known cargoes of the particular myosin XI;
      however, certain myosin XI YFP fusions labeled organelles that had not previously
      been found to be detectably affected by mutations nor by expression of dominant
      negative constructs.

PMID- 22645549
TI  - At the Frontier; RXLR Effectors Crossing the Phytophthora-Host Interface.
AB  - Plants are constantly beset by pathogenic organisms. To successfully infect their
      hosts, plant pathogens secrete effector proteins, many of which are translocated
      to the inside of the host cell where they manipulate normal physiological
      processes and undermine host defense. The way by which effectors cross the
      frontier to reach the inside of the host cell varies among different classes of
      pathogens. For oomycete plant pathogens - like the potato late blight pathogen
      Phytophthora infestans - it has been shown that effector translocation to the
      host cell cytoplasm is dependent on conserved amino acid motifs that are present
      in the N-terminal part of effector proteins. One of these motifs, known as the
      RXLR motif, has a strong resemblance with a host translocation motif found in
      effectors secreted by Plasmodium species. These malaria parasites, that reside
      inside specialized vacuoles in red blood cells, make use of a specific protein
      translocation complex to export effectors from the vacuole into the red blood
      cell. Whether or not also oomycete RXLR effectors require a translocation complex
      to cross the frontier is still under investigation. For one P. infestans RXLR
      effector named IPI-O we have found a potential host target that could play a role
      in establishing the first contact between this effector and the host cell. This
      membrane spanning lectin receptor kinase, LecRK-I.9, interacts with IPI-O via the
      tripeptide RGD that overlaps with the RXLR motif. In animals, RGD is a well-known
      cell adhesion motif; it binds to integrins, which are membrane receptors that
      regulate many cellular processes and which can be hijacked by pathogens for
      either effector translocation or pathogen entry into host cells.

PMID- 22645551
TI  - The bZIP Transcription Factor PERIANTHIA: A Multifunctional Hub for Meristem
      Control.
AB  - As sessile organisms, plants are exposed to extreme variations in environmental
      conditions over the course of their lives. Since plants grow and initiate new
      organs continuously, they have to modulate the underlying developmental program
      accordingly to cope with this challenge. At the heart of this extraordinary
      developmental plasticity are pluripotent stem cells, which are maintained during
      the entire life-cycle of the plant and that are embedded within dynamic stem cell
      niches. While the complex regulatory principles of plant stem cell control under
      artificial constant growth conditions begin to emerge, virtually nothing is known
      about how this circuit adapts to variations in the environment. In addition to
      the local feedback system constituted by the homeodomain transcription factor
      WUSCHEL (WUS) and the CLAVATA signaling cascade in the center of the shoot apical
      meristem (SAM), the bZIP transcription factor PERIANTHIA (PAN) not only has a
      broader expression domain in SAM and flowers, but also carries out more diverse
      functions in meristem maintenance: pan mutants show alterations in environmental
      response, shoot meristem size, floral organ number, and exhibit severe defects in
      termination of floral stem cells in an environment dependent fashion. Genetic and
      genomic analyses indicate that PAN interacts with a plethora of developmental
      pathways including light, plant hormone, and meristem control systems, suggesting
      that PAN is as an important regulatory node in the network of plant stem cell
      control.

PMID- 22645550
TI  - Next generation quantitative genetics in plants.
AB  - Most characteristics in living organisms show continuous variation, which
      suggests that they are controlled by multiple genes. Quantitative trait loci
      (QTL) analysis can identify the genes underlying continuous traits by
      establishing associations between genetic markers and observed phenotypic
      variation in a segregating population. The new high-throughput sequencing (HTS)
      technologies greatly facilitate QTL analysis by providing genetic markers at
      genome-wide resolution in any species without previous knowledge of its genome.
      In addition HTS serves to quantify molecular phenotypes, which aids to identify
      the loci responsible for QTLs and to understand the mechanisms underlying
      diversity. The constant improvements in price, experimental protocols,
      computational pipelines, and statistical frameworks are making feasible the use
      of HTS for any research group interested in quantitative genetics. In this review
      I discuss the application of HTS for molecular marker discovery, population
      genotyping, and expression profiling in QTL analysis.

PMID- 22645552
TI  - Physiological limits to zinc biofortification of edible crops.
AB  - It has been estimated that one-third of the world's population lack sufficient Zn
      for adequate nutrition. This can be alleviated by increasing dietary Zn intakes
      through Zn biofortification of edible crops. Biofortification strategies include
      the application of Zn-fertilizers and the development of crop genotypes that
      acquire more Zn from the soil and accumulate it in edible portions. Zinc
      concentrations in roots, leaves, and stems can be increased through the
      application of Zn-fertilizers. Root Zn concentrations of up to 500-5000 mg kg(-1)
      dry matter (DM), and leaf Zn concentrations of up to 100-700 mg kg(-1) DM, can be
      achieved without loss of yield when Zn-fertilizers are applied to the soil. It is
      possible that greater Zn concentrations in non-woody shoot tissues can be
      achieved using foliar Zn-fertilizers. By contrast, Zn concentrations in fruits,
      seeds, and tubers are severely limited by low Zn mobility in the phloem and Zn
      concentrations higher than 30-100 mg kg(-1) DM are rarely observed. However,
      genetically modified plants with improved abilities to translocate Zn in the
      phloem might be used to biofortify these phloem-fed tissues. In addition,
      genetically modified plants with increased tolerance to high tissue Zn
      concentrations could be used to increase Zn concentrations in all edible produce
      and, thereby, increase dietary Zn intakes.

PMID- 22645553
TI  - Phosphate Import in Plants: Focus on the PHT1 Transporters.
AB  - The main source of phosphorus for plants is inorganic phosphate (Pi), which is
      characterized by its poor availability and low mobility. Uptake of this element
      from the soil relies heavily upon the PHT1 transporters, a specific family of
      plant plasma membrane proteins that were identified by homology with the yeast
      PHO84 Pi transporter. Since the discovery of PHT1 transporters in 1996, various
      studies have revealed that their function is controlled by a highly complex
      network of regulation. This review will summarize the current state of research
      on plant PHT1 multigenic families, including physiological, biochemical,
      molecular, cellular, and genetics studies.

PMID- 22645554
TI  - Hijacking of the Host SCF Ubiquitin Ligase Machinery by Plant Pathogens.
AB  - The SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex mediates
      polyubiquitination of proteins targeted for degradation, thereby controlling a
      plethora of biological processes in eukaryotic cells. Although this
      ubiquitination machinery is found and functional only in eukaryotes, many non
      eukaryotic pathogens also encode F-box proteins, the critical subunits of the SCF
      complex. Increasing evidence indicates that such non-eukaryotic F-box proteins
      play an essential role in subverting or exploiting the host ubiquitin/proteasome
      system for efficient pathogen infection. A recent bioinformatic analysis has
      identified more than 70 F-box proteins in 22 different bacterial species,
      suggesting that use of pathogen-encoded F-box effectors in the host cell may be a
      widespread infection strategy. In this review, we focus on plant pathogen-encoded
      F-box effectors, such as VirF of Agrobacterium tumefaciens, GALAs of Ralstonia
      solanacearum, and P0 of Poleroviruses, and discuss the molecular mechanism by
      which plant pathogens use these factors to manipulate the host cell for their own
      benefit.

PMID- 22645555
TI  - A genome-wide survey for Arabidopsis leucine-rich repeat receptor kinases
      implicated in plant immunity.
AB  - Receptor-like kinases (RLK) are among the largest gene families encoded by plant
      genomes. Common structural features of plant RLKs are an extracellular ligand
      binding domain, a membrane spanning domain, and an intracellular protein kinase
      domain. The largest subfamily of plant RLKs is characterized by extracellular
      leucine-rich repeat (LRR-RLK) structures that are known biochemical modules for
      mediating ligand binding and protein-protein interactions. In the frame of the
      Arabidopsis Functional Genomics Network initiative of the German Research
      Foundation (DFG) we have conducted a comprehensive survey for and functional
      characterization of LRR-RLKs potentially implicated in Arabidopsis thaliana
      immunity to microbial infection. Arabidopsis gene expression patterns suggested
      an important role of this class of proteins in biotic stress adaptation. Detailed
      biochemical and physiological characterization of the brassinosteroid insensitive
      1-associated receptor kinase 1 (BAK1) revealed brassinolide-independent roles of
      this protein in plant immunity, in addition to its well-established function in
      plant development. The LRR-RLK BAK1 has further been shown to form heteromeric
      complexes with various other LRR-RLKs in a ligand-dependent manner, suggesting a
      role as adapter or co-receptor in plant receptor complexes. Here, we review the
      current status of BAK1 and BAK1-interacting LRR-RLKs in plant immunity.

PMID- 22645556
TI  - Dynamic network-based epistasis analysis: boolean examples.
AB  - In this article we focus on how the hierarchical and single-path assumptions of
      epistasis analysis can bias the inference of gene regulatory networks. Here we
      emphasize the critical importance of dynamic analyses, and specifically
      illustrate the use of Boolean network models. Epistasis in a broad sense refers
      to gene interactions, however, as originally proposed by Bateson, epistasis is
      defined as the blocking of a particular allelic effect due to the effect of
      another allele at a different locus (herein, classical epistasis). Classical
      epistasis analysis has proven powerful and useful, allowing researchers to infer
      and assign directionality to gene interactions. As larger data sets are becoming
      available, the analysis of classical epistasis is being complemented with
      computer science tools and system biology approaches. We show that when the
      hierarchical and single-path assumptions are not met in classical epistasis
      analysis, the access to relevant information and the correct inference of gene
      interaction topologies is hindered, and it becomes necessary to consider the
      temporal dynamics of gene interactions. The use of dynamical networks can
      overcome these limitations. We particularly focus on the use of Boolean networks
      that, like classical epistasis analysis, relies on logical formalisms, and hence
      can complement classical epistasis analysis and relax its assumptions. We develop
      a couple of theoretical examples and analyze them from a dynamic Boolean network
      model perspective. Boolean networks could help to guide additional experiments
      and discern among alternative regulatory schemes that would be impossible or
      difficult to infer without the elimination of these assumption from the classical
      epistasis analysis. We also use examples from the literature to show how a
      Boolean network-based approach has resolved ambiguities and guided epistasis
      analysis. Our article complements previous accounts, not only by focusing on the
      implications of the hierarchical and single-path assumption, but also by
      demonstrating the importance of considering temporal dynamics, and specifically
      introducing the usefulness of Boolean network models and also reviewing some key
      properties of network approaches.

PMID- 22645557
TI  - When Double is not Twice as Much.
AB  - Gene and genome duplications provide a playground for various selective pressures
      and contribute significantly to genome complexity. It is assumed that the genomes
      of all major eukaryotic lineages possess duplicated regions that result from gene
      and genome duplication. There is evidence that the model plant Arabidopsis has
      been subjected to at least three whole-genome duplication events over the last
      150-200 million years. As a result, many cellular processes are governed by
      redundantly acting gene families. Plants pass through two distinct life phases
      with a haploid gametophytic alternating with a diploid sporophytic generation.
      This ontogenetic difference in gene copy number has important implications for
      the outcome of deleterious mutations, which are masked by the second gene copy in
      diploid systems but expressed in a dominant fashion in haploid organisms. As a
      consequence, maintaining the activity of duplicated genes might be particularly
      advantageous during the haploid gametophytic generation. Here, we describe the
      distinctive features associated with the alteration of generations and discuss
      how activity profiles of duplicated genes might get modulated in a life phase
      dependent fashion.

PMID- 22645558
TI  - Evidence for a DNA-Based Mechanism of Intron-Mediated Enhancement.
AB  - Many introns significantly increase gene expression through a process termed
      intron-mediated enhancement (IME). Introns exist in the transcribed DNA and the
      nascent RNA, and could affect expression from either location. To determine which
      is more relevant to IME, hybrid introns were constructed that contain sequences
      from stimulating Arabidopsis thaliana introns either in their normal orientation
      or as the reverse complement. Both ends of each intron are from the non
      stimulatory COR15a intron in their normal orientation to allow splicing. The
      inversions create major alterations to the sequence of the transcribed RNA with
      relatively minor changes to the DNA structure. Introns containing portions of
      either the UBQ10 or ATPK1 intron increased expression to a similar degree
      regardless of orientation. Also, computational predictions of IME improve when
      both intron strands are considered. These findings are more consistent with
      models of IME that act at the level of DNA rather than RNA.

PMID- 22645560
TI  - Gibberellin signaling in plants - the extended version.
AB  - The plant hormone gibberellin (GA) controls major aspects of plant growth such as
      germination, elongation growth, flower development, and flowering time. In recent
      years, a number of studies have revealed less apparent roles for GA in a
      surprisingly broad set of developmental as well as cell biological processes. The
      identification of GA receptor proteins on the one end of the signaling cascade,
      DELLA proteins as central repressors of the pathway and transcription regulators
      such as the phytochrome interacting factors and the GATA-type transcription
      factors GNC and CGA1/GNL on the current other end of the signaling cascade have
      extended our knowledge about how GA and DELLAs regulate a diverse set of plant
      responses.

PMID- 22645559
TI  - Defining the plant peroxisomal proteome: from Arabidopsis to rice.
AB  - Peroxisomes are small subcellular organelles mediating a multitude of processes
      in plants. Proteomics studies over the last several years have yielded much
      needed information on the composition of plant peroxisomes. In this review, the
      status of peroxisome proteomics studies in Arabidopsis and other plant species
      and the cumulative advances made through these studies are summarized. A
      reference Arabidopsis peroxisome proteome is generated, and some unique aspects
      of Arabidopsis peroxisomes that were uncovered through proteomics studies and
      hint at unanticipated peroxisomal functions are also highlighted. Knowledge
      gained from Arabidopsis was utilized to compile a tentative list of peroxisome
      proteins for the model monocot plant, rice. Differences in the peroxisomal
      proteome between these two model plants were drawn, and novel facets in rice were
      expounded upon. Finally, we discuss about the current limitations of experimental
      proteomics in decoding the complete and dynamic makeup of peroxisomes, and
      complementary and integrated approaches that would be beneficial to defining the
      peroxisomal metabolic and regulatory roadmaps. The synteny of genomes in the
      grass family makes rice an ideal model to study peroxisomes in cereal crops, in
      which these organelles have received much less attention, with the ultimate goal
      to improve crop yield.

PMID- 22645562
TI  - The Expression of Petunia Strigolactone Pathway Genes is Altered as Part of the
      Endogenous Developmental Program.
AB  - Analysis of mutants with increased branching has revealed the strigolactone
      synthesis/perception pathway which regulates branching in plants. However,
      whether variation in this well conserved developmental signaling system
      contributes to the unique plant architectures of different species is yet to be
      determined. We examined petunia orthologs of the ArabidopsisMAX1 and MAX2 genes
      to characterize their role in petunia architecture. A single ortholog of MAX1,
      PhMAX1 which encodes a cytochrome P450, was identified and was able to complement
      the max1 mutant of Arabidopsis. Petunia has two copies of the MAX2 gene, PhMAX2A
      and PhMAX2B which encode F-Box proteins. Differences in the transcript levels of
      these two MAX2-like genes suggest diverging functions. Unlike PhMAX2B, PhMAX2A
      mRNA levels change in leaves of differing age/position on the plant. Nonetheless,
      this gene functionally complements the Arabidopsismax2 mutant indicating that the
      biochemical activity of the PhMAX2A protein is not significantly different from
      MAX2. The expression of the petunia strigolactone pathway genes (PhCCD7, PhCCD8,
      PhMAX1, PhMAX2A, and PhMAX2B) was then further investigated throughout the
      development of wild-type petunia plants. Three of these genes showed changes in
      mRNA levels over a development series. Alterations to the expression patterns of
      these genes may influence the branching growth habit of plants by changing
      strigolactone production and/or sensitivity. These changes could allow both
      subtle and dramatic changes to branching within and between species.

PMID- 22645563
TI  - Protein Phylogenetic Analysis of Ca(2+)/cation Antiporters and Insights into
      their Evolution in Plants.
AB  - Cation transport is a critical process in all organisms and is essential for
      mineral nutrition, ion stress tolerance, and signal transduction. Transporters
      that are members of the Ca(2+)/cation antiporter (CaCA) superfamily are involved
      in the transport of Ca(2+) and/or other cations using the counter exchange of
      another ion such as H(+) or Na(+). The CaCA superfamily has been previously
      divided into five transporter families: the YRBG, Na(+)/Ca(2+) exchanger (NCX),
      Na(+)/Ca(2+), K(+) exchanger (NCKX), H(+)/cation exchanger (CAX), and
      cation/Ca(2+) exchanger (CCX) families, which include the well-characterized NCX
      and CAX transporters. To examine the evolution of CaCA transporters within higher
      plants and the green plant lineage, CaCA genes were identified from the genomes
      of sequenced flowering plants, a bryophyte, lycophyte, and freshwater and marine
      algae, and compared with those from non-plant species. We found evidence of the
      expansion and increased diversity of flowering plant genes within the CAX and CCX
      families. Genes related to the NCX family are present in land plant though they
      encode distinct MHX homologs which probably have an altered transport function.
      In contrast, the NCX and NCKX genes which are absent in land plants have been
      retained in many species of algae, especially the marine algae, indicating that
      these organisms may share "animal-like" characteristics of Ca(2+) homeostasis and
      signaling. A group of genes encoding novel CAX-like proteins containing an EF
      hand domain were identified from plants and selected algae but appeared to be
      lacking in any other species. Lack of functional data for most of the CaCA
      proteins make it impossible to reliably predict substrate specificity and
      function for many of the groups or individual proteins. The abundance and
      diversity of CaCA genes throughout all branches of life indicates the importance
      of this class of cation transporter, and that many transporters with novel
      functions are waiting to be discovered.

PMID- 22645561
TI  - Membrane traffic and fusion at post-Golgi compartments.
AB  - Complete sequencing of the Arabidopsis genome a decade ago has facilitated the
      functional analysis of various biological processes including membrane traffic by
      which many proteins are delivered to their sites of action and turnover. In
      particular, membrane traffic between post-Golgi compartments plays an important
      role in cell signaling, taking care of receptor-ligand interaction and
      inactivation, which requires secretion, endocytosis, and recycling or targeting
      to the vacuole for degradation. Here, we discuss recent studies that address the
      identity of post-Golgi compartments, the machinery involved in traffic and fusion
      or functionally characterized cargo proteins that are delivered to or pass
      through post-Golgi compartments. We also provide an outlook on future challenges
      in this area of research.

PMID- 22645564
TI  - Transport proteins regulate the flux of metabolites and cofactors across the
      membrane of plant peroxisomes.
AB  - In land plants, peroxisomes play key roles in various metabolic pathways,
      including the most prominent examples, that is lipid mobilization and
      photorespiration. Given the large number of substrates that are exchanged across
      the peroxisomal membrane, a wide spectrum of metabolite and cofactor transporters
      is required and needs to be efficiently coordinated. These peroxisomal transport
      proteins are a prerequisite for metabolic reactions inside plant peroxisomes. The
      entire peroxisomal "permeome" is closely linked to the adaption of photosynthetic
      organisms during land plant evolution to fulfill and optimize their new metabolic
      demands in cells, tissues, and organs. This review assesses for the first time
      the distribution of these peroxisomal transporters within the algal and plant
      species underlining their evolutionary relevance. Despite the importance of
      peroxisomal transporters, the majority of these proteins, however, are still
      unknown at the molecular level in plants as well as in other eukaryotic
      organisms. Four transport proteins have been recently identified and functionally
      characterized in Arabidopsis so far: one transporter for the import of fatty
      acids and three carrier proteins for the uptake of the cofactors ATP and NAD into
      plant peroxisomes. The transport of the three substrates across the peroxisomal
      membrane is essential for the degradation of fatty acids and fatty acids-related
      compounds via beta-oxidation. This metabolic pathway plays multiple functions for
      growth and development in plants that have been crucial in land plant evolution.
      In this review, we describe the current state of their physiological roles in
      Arabidopsis and discuss novel features in their putative transport mechanisms.

PMID- 22645565
TI  - TriAnnot: A Versatile and High Performance Pipeline for the Automated Annotation
      of Plant Genomes.
AB  - In support of the international effort to obtain a reference sequence of the
      bread wheat genome and to provide plant communities dealing with large and
      complex genomes with a versatile, easy-to-use online automated tool for
      annotation, we have developed the TriAnnot pipeline. Its modular architecture
      allows for the annotation and masking of transposable elements, the structural,
      and functional annotation of protein-coding genes with an evidence-based quality
      indexing, and the identification of conserved non-coding sequences and molecular
      markers. The TriAnnot pipeline is parallelized on a 712 CPU computing cluster
      that can run a 1-Gb sequence annotation in less than 5 days. It is accessible
      through a web interface for small scale analyses or through a server for large
      scale annotations. The performance of TriAnnot was evaluated in terms of
      sensitivity, specificity, and general fitness using curated reference sequence
      sets from rice and wheat. In less than 8 h, TriAnnot was able to predict more
      than 83% of the 3,748 CDS from rice chromosome 1 with a fitness of 67.4%. On a
      set of 12 reference Mb-sized contigs from wheat chromosome 3B, TriAnnot predicted
      and annotated 93.3% of the genes among which 54% were perfectly identified in
      accordance with the reference annotation. It also allowed the curation of 12
      genes based on new biological evidences, increasing the percentage of perfect
      gene prediction to 63%. TriAnnot systematically showed a higher fitness than
      other annotation pipelines that are not improved for wheat. As it is easily
      adaptable to the annotation of other plant genomes, TriAnnot should become a
      useful resource for the annotation of large and complex genomes in the future.

PMID- 22645566
TI  - Dynamic Remodeling of the Plastid Envelope Membranes - A Tool for Chloroplast
      Envelope in vivo Localizations.
AB  - Two envelope membranes delimit plastids, the defining organelles of plant cells.
      The inner and outer envelope membranes are unique in their protein and lipid
      composition. Several studies have attempted to establish the proteome of these
      two membranes; however, differentiating between them is difficult due to their
      close proximity. Here, we describe a novel approach to distinguish the
      localization of proteins between the two membranes using a straightforward
      approach based on live cell imaging coupled with transient expression. We base
      our approach on analyses of the distribution of GFP-fusions, which were aimed to
      verify outer envelope membrane proteomics data. To distinguish between outer
      envelope and inner envelope protein localization, we used AtTOC64-GFP and AtTIC40
      GFP, as respective controls. During our analyses, we observed membrane
      proliferations and loss of chloroplast shape in conditions of protein over
      expression. The morphology of the proliferations varied in correlation with the
      suborganellar distribution of the over-expressed proteins. In particular, while
      layers of membranes built up in the inner envelope membrane, the outer envelope
      formed long extensions into the cytosol. Using electron microscopy, we showed
      that these extensions were stromules, a dynamic feature of plastids. Since the
      behavior of the membranes is different and is related to the protein
      localization, we propose that in vivo studies based on the analysis of
      morphological differences of the membranes can be used to distinguish between
      inner and outer envelope localizations of proteins. To demonstrate the
      applicability of this approach, we demonstrated the localization of AtLACS9 to
      the outer envelope membrane. We also discuss protein impact on membrane behavior
      and regulation of protein insertion into membranes, and provide new hypotheses on
      the formation of stromules.

PMID- 22645567
TI  - Multiple Transport Pathways for Mediating Intracellular pH Homeostasis: The
      Contribution of H(+)/ion Exchangers.
AB  - Intracellular pH homeostasis is an essential process in all plant cells. The
      transport of H(+) into intracellular compartments is critical for providing pH
      regulation. The maintenance of correct luminal pH in the vacuole and in
      compartments of the secretory/endocytic pathway is important for a variety of
      cellular functions including protein modification, sorting, and trafficking. It
      is becoming increasingly evident that coordination between primary H(+) pumps,
      most notably the V-ATPase, and secondary ion/H(+) exchangers allows this
      endomembrane pH maintenance to occur. This article describes some of the recent
      insights from the studies of plant cation/H(+) exchangers and anion/H(+)
      exchangers that demonstrate the fundamental roles of these transporters in pH
      homeostasis within intracellular compartments.

PMID- 22645568
TI  - Model Misinterpretation within Biology: Phenotypes, Statistics, Networks, and
      Inference.
AB  - Models of myriad forms are rapidly becoming central to biology. These range from
      statistical models that are fundamental to the interpretation of experimental
      results to ordinary differential equation models that attempt to describe the
      results in a mechanistic format. Models will be more and more essential to
      biologists but this growing importance requires all model users to become more
      sophisticated about what is in a model and how that limits the usability of the
      model. This review attempts to relay the potential pitfalls that can lie within a
      model.

PMID- 22645569
TI  - The Nucleocapsid Protein of Potato Yellow dwarf Virus: Protein Interactions and
      Nuclear Import Mediated by a Non-Canonical Nuclear Localization Signal.
AB  - Potato yellow dwarf virus (PYDV) is the type species of the genus
      Nucleorhabdovirus and, like all members of this genus, replication and
      morphogenesis occurs inside the nuclei of infected cells. Protein localization
      prediction algorithms failed to identify a nuclear localization signal (NLS) in
      PYDV nucleocapsid (N) protein, although PYDV-N has been shown to localize
      exclusively to the nucleus when expressed as a green fluorescent protein (GFP):N
      fusion in plant cells. Deletion analysis using fragments of PYDV-N identified a
      karyophilic region in the carboxy-terminal 122 amino acids. Alanine-scanning
      mutagenesis was performed across this region in the context of the full-length N
      protein. Mutants were assayed for their ability to nuclear localize using live
      cell imaging and a yeast-based assay. Two amino acid motifs, (419)QKR(421) and
      (432)KR(433) were shown to be essential for nuclear import and interaction with
      importin-alpha. Additional bimolecular fluorescence complementation showed that
      the PYDV-N-NLS mutants cannot be ferried into the nucleus via interaction with
      PYDV-P or -M. In contrast, interaction with N-NLS mutants appeared to retard the
      nuclear import of PYDV-P. GFP fused to aa 419-434 established that the PYDV-N-NLS
      can function outside the context of this protein. Taken together, it was
      determined that PYDV-N contains the bipartite NLS (419)QKRANEEAPPAAQKR(433).

PMID- 22645570
TI  - Metabolomics as a Hypothesis-Generating Functional Genomics Tool for the
      Annotation of Arabidopsis thaliana Genes of "Unknown Function".
AB  - Metabolomics is the methodology that identifies and measures global pools of
      small molecules (of less than about 1,000 Da) of a biological sample, which are
      collectively called the metabolome. Metabolomics can therefore reveal the
      metabolic outcome of a genetic or environmental perturbation of a metabolic
      regulatory network, and thus provide insights into the structure and regulation
      of that network. Because of the chemical complexity of the metabolome and
      limitations associated with individual analytical platforms for determining the
      metabolome, it is currently difficult to capture the complete metabolome of an
      organism or tissue, which is in contrast to genomics and transcriptomics. This
      paper describes the analysis of Arabidopsis metabolomics data sets acquired by a
      consortium that includes five analytical laboratories, bioinformaticists, and
      biostatisticians, which aims to develop and validate metabolomics as a hypothesis
      generating functional genomics tool. The consortium is determining the
      metabolomes of Arabidopsis T-DNA mutant stocks, grown in standardized controlled
      environment optimized to minimize environmental impacts on the metabolomes.
      Metabolomics data were generated with seven analytical platforms, and the
      combined data is being provided to the research community to formulate initial
      hypotheses about genes of unknown function (GUFs). A public database
      (www.PlantMetabolomics.org) has been developed to provide the scientific
      community with access to the data along with tools to allow for its interactive
      analysis. Exemplary datasets are discussed to validate the approach, which
      illustrate how initial hypotheses can be generated from the consortium-produced
      metabolomics data, integrated with prior knowledge to provide a testable
      hypothesis concerning the functionality of GUFs.

PMID- 22645571
TI  - Diversification and Expression of the PIN, AUX/LAX, and ABCB Families of Putative
      Auxin Transporters in Populus.
AB  - Intercellular transport of the plant hormone auxin is mediated by three families
      of membrane-bound protein carriers, with the PIN and ABCB families coding
      primarily for efflux proteins and the AUX/LAX family coding for influx proteins.
      In the last decade our understanding of gene and protein function for these
      transporters in Arabidopsis has expanded rapidly but very little is known about
      their role in woody plant development. Here we present a comprehensive account of
      all three families in the model woody species Populus, including chromosome
      distribution, protein structure, quantitative gene expression, and evolutionary
      relationships. The PIN and AUX/LAX gene families in Populus comprise 16 and 8
      members respectively and show evidence for the retention of paralogs following a
      relatively recent whole genome duplication. There is also differential expression
      across tissues within many gene pairs. The ABCB family is previously undescribed
      in Populus and includes 20 members, showing a much deeper evolutionary history,
      including both tandem and whole genome duplication as well as probable gene loss.
      A striking number of these transporters are expressed in developing Populus stems
      and we suggest that evolutionary and structural relationships with known auxin
      transporters in Arabidopsis can point toward candidate genes for further study in
      Populus. This is especially important for the ABCBs, which is a large family and
      includes members in Arabidopsis that are able to transport other substrates in
      addition to auxin. Protein modeling, sequence alignment and expression data all
      point to ABCB1.1 as a likely auxin transport protein in Populus. Given that
      basipetal auxin flow through the cambial zone shapes the development of woody
      stems, it is important that we identify the full complement of genes involved in
      this process. This work should lay the foundation for studies targeting specific
      proteins for functional characterization and in situ localization.

PMID- 22645573
TI  - Epigenetic Modifications during Angiosperm Gametogenesis.
AB  - Angiosperms do not contain a distinct germline, but rather develop gametes from
      gametophyte initials that undergo cell division. These gametes contain cells that
      give rise to an endosperm and the embryo. DNA methylation is decreased in the
      vegetative nucleus (VN) and central cell nuclei (CCN) resulting in expression of
      transposable elements (TEs). It is thought that the siRNAs produced in response
      to TE expression are able to travel to the sperm cells and egg cells (EC) from VN
      and CCN, respectively, in order to enforce silencing there. Demethylation during
      gametogenesis helps ensure that even newly integrated TEs are expressed and
      therefore silenced by the resulting siRNA production. A final form of epigenetic
      control is modification of histones, which includes accumulation of the H3
      variant HTR10 in mature sperm that is then completely replaced following
      fertilization. In females, the histone isoforms present in the EC and CCN differ,
      potentially helping to differentiate the two components during gametogenesis.

PMID- 22645574
TI  - Molecular Evolution of Plant AAP and LHT Amino Acid Transporters.
AB  - Nitrogen is an essential mineral nutrient and it is often transported within
      living organisms in its reduced form, as amino acids. Transport of amino acids
      across cellular membranes requires proteins, and here we report the phylogenetic
      analysis across taxa of two amino acid transporter families, the amino acid
      permeases (AAPs) and the lysine-histidine-like transporters (LHTs). We found that
      the two transporter families form two distinct groups in plants supporting the
      concept that both are essential. AAP transporters seem to be restricted to land
      plants. They were found in Selaginella moellendorffii and Physcomitrella patens
      but not in Chlorophyte, Charophyte, or Rhodophyte algae. AAPs were strongly
      represented in vascular plants, consistent with their major function in phloem
      (vascular tissue) loading of amino acids for sink nitrogen supply. LHTs on the
      other hand appeared prior to land plants. LHTs were not found in chlorophyte
      algae Chlamydomonas reinhardtii and Volvox carterii. However, the characean alga
      Klebsormidium flaccidum encodes KfLHT13 and phylogenetic analysis indicates that
      it is basal to land plant LHTs. This is consistent with the hypothesis that
      characean algae are ancestral to land plants. LHTs were also found in both S.
      moellendorffii and P. patens as well as in monocots and eudicots. To date, AAPs
      and LHTs have mainly been characterized in Arabidopsis (eudicots) and these
      studies provide clues to the functions of the newly identified homologs.

PMID- 22645572
TI  - Deciphering the plant splicing code: experimental and computational approaches
      for predicting alternative splicing and splicing regulatory elements.
AB  - Extensive alternative splicing (AS) of precursor mRNAs (pre-mRNAs) in
      multicellular eukaryotes increases the protein-coding capacity of a genome and
      allows novel ways to regulate gene expression. In flowering plants, up to 48% of
      intron-containing genes exhibit AS. However, the full extent of AS in plants is
      not yet known, as only a few high-throughput RNA-Seq studies have been performed.
      As the cost of obtaining RNA-Seq reads continues to fall, it is anticipated that
      huge amounts of plant sequence data will accumulate and help in obtaining a more
      complete picture of AS in plants. Although it is not an onerous task to obtain
      hundreds of millions of reads using high-throughput sequencing technologies,
      computational tools to accurately predict and visualize AS are still being
      developed and refined. This review will discuss the tools to predict and
      visualize transcriptome-wide AS in plants using short-reads and highlight their
      limitations. Comparative studies of AS events between plants and animals have
      revealed that there are major differences in the most prevalent types of AS
      events, suggesting that plants and animals differ in the way they recognize exons
      and introns. Extensive studies have been performed in animals to identify cis
      elements involved in regulating AS, especially in exon skipping. However, few
      such studies have been carried out in plants. Here, we review the current state
      of research on splicing regulatory elements (SREs) and briefly discuss emerging
      experimental and computational tools to identify cis-elements involved in
      regulation of AS in plants. The availability of curated alternative splice forms
      in plants makes it possible to use computational tools to predict SREs involved
      in AS regulation, which can then be verified experimentally. Such studies will
      permit identification of plant-specific features involved in AS regulation and
      contribute to deciphering the splicing code in plants.

PMID- 22645575
TI  - SUT Sucrose and MST Monosaccharide Transporter Inventory of the Selaginella
      Genome.
AB  - Most metazoa use hexose transporters to acquire hexoses from their diet and as a
      transport form for distributing carbon and energy within their bodies; insects
      use trehalose, and plants use sucrose as their major form for translocation.
      Plant genomes contain at least three families of mono- and disaccharide
      transporters: monosaccharide/polyol transporters that are evolutionary closely
      related to the yeast and human glucose transporters, sucrose transporters of the
      SUT family, which similar to the hexose transporters belong to the major
      facilitator superfamily, but share only minimal amino acid sequence homology with
      the hexose transporters, and the family of SWEET sugar transporters conserved
      between animals and plants. Recently, the genome sequence of the spikemoss
      Selaginella has been determined. In order to study the evolution of sugar
      transport in plants, we carefully annotated of the complement of sugar
      transporters in Selaginella. We review the current knowledge regarding sugar
      transport in spikemoss and provide phylogenetic analyses of the complement of MST
      and SUT homologs in Selaginella (and Physcomitrella).

PMID- 22645576
TI  - Biochemical and Molecular-Genetic Characterization of SFD1's Involvement in Lipid
      Metabolism and Defense Signaling.
AB  - The Arabidopsis thaliana SFD1 (suppressor of fatty acid desaturase deficiency1)
      gene (also known as GLY1) is required for accumulation of 34:6 (i.e., 18:3-16:3)
      monogalactosyldiacylglycerol (MGDG) and for the activation of systemic acquired
      resistance (SAR), an inducible defense mechanism that confers resistance against
      a broad spectrum of pathogens. SFD1, which has been suggested to be involved in
      lipid-based signaling in SAR, contains a putative chloroplast transit peptide and
      has glycerol-3-phosphate synthesizing dihydroxyacetone phosphate (DHAP) reductase
      (also referred as glycerol-3-phosphate dehydrogenase) activity. The goals of this
      study were to determine if the DHAP reductase activity and chloroplast
      localization are required for SFD1's involvement in galactolipid metabolism and
      SAR signaling. The crystal structure of a Leishmania mexicana glycerol-3
      phosphate dehydrogenase was used to model SFD1 structure and identify Lys194,
      Lys279, and Asp332 as potential catalytic site residues in SFD1. Mutational
      analysis of SFD1 confirmed that Lys194, Lys279, and Asp332 are critical for
      SFD1's DHAP reductase activity, and its involvement in SAR. SFD1 proteins with
      these residues individually substituted by Ala lacked DHAP reductase activity and
      were unable to complement the SAR defect of the sfd1 mutant. The SFD1-Ala279
      protein was also unable to restore 34:6-MGDG content when expressed in the sfd1
      mutant. In vivo imaging of a green fluorescent protein-tagged SFD1 protein
      demonstrated that SFD1 is targeted to the chloroplast. The N-terminal 43 amino
      acids, which are required for proper targeting of SFD1 to the chloroplast, are
      also required for SFD1's function in lipid metabolism and SAR. Taken together,
      these results demonstrate that SFD1's DHAP reductase activity is required in the
      chloroplast for lipid metabolism and defense signaling.

PMID- 22645577
TI  - Future prospects for ascochyta blight resistance breeding in cool season food
      legumes.
AB  - Legume cultivation is strongly hampered by the occurrence of ascochyta blights.
      Strategies of control have been developed but only marginal successes achieved.
      Breeding for disease resistance is regarded the most cost efficient method of
      control. Significant genetic variation for disease resistance exists in most
      legume crops with numerous germplasm lines maintained, providing an excellent
      resource for plant breeders. Fast and reliable screening methods have been
      adjusted to fulfill breeding program needs. However, the complex inheritance
      controlled quantitatively by multiple genes, has been difficult to manipulate.
      Successful application of biotechnology to ascochyta blight resistance breeding
      in legume crops will facilitate a good biological knowledge both of the crops
      pathogen interaction and of the mechanisms underlying resistance. The current
      focus in applied breeding is leveraging biotechnological tools to develop more
      and better markers to speed up the delivery of improved cultivars to the farmer.
      To date, however, progress in marker development and delivery of useful markers
      has been slow in most legumes. The limited saturation of the genomic regions
      bearing putative QTLs in legume crops makes difficult to identify the most
      tightly linked markers and to determine the accurate position of QTLs. The
      application of next generation sequencing technologies will contribute to the
      development of new markers and the identification of candidate genes for
      ascochyta blight resistance.

PMID- 22645578
TI  - Maize provitamin a carotenoids, current resources, and future metabolic
      engineering challenges.
AB  - Vitamin A deficiency is a serious global health problem that can be alleviated by
      improved nutrition. Development of cereal crops with increased provitamin A
      carotenoids can provide a sustainable solution to eliminating vitamin A
      deficiency worldwide. Maize is a model for cereals and a major staple
      carbohydrate source. Here, we discuss maize carotenogenesis with regard to
      pathway regulation, available resources, and current knowledge for improving
      carotenoid content and levels of provitamin A carotenoids in edible maize
      endosperm. This knowledge will be applied to improve the nutritional composition
      of related Poaceae crops. We discuss opportunities and challenges for optimizing
      provitamin A carotenoid biofortification of cereal food crops.

PMID- 22645579
TI  - Plasmodesmata "in Communicado".
AB  - Cell-to-cell communication is fundamental to multicellular life. For this to
      occur effectively there must be pathways and dynamic networks for communication.
      These might depend upon electrical or chemical signals or the mass transfer of
      molecules between adjacent cells. Molecular communication occurs either via an
      extra-cellular pathway or through physical structures, called plasmodesmata, that
      connect the cytoplasm of neighboring cells. Plasmodesmata bridge the rigid
      physical barrier presented by the cell wall to extend the symplasm from single
      cells to tissue domains that have functional importance for tissue growth,
      development, and defense. Although recent years have seen advances in our
      knowledge of the physical nature of PD, the trafficked molecules, and of the
      wider processes they affect, our knowledge of PD structure and function is still
      relatively rudimentary. This article will consider the technical/experimental
      difficulties hindering PD research and suggest priorities in the future research
      effort that might advance the field at a significantly faster rate.

PMID- 22645580
TI  - Overexpression of Fatty Acid Amide Hydrolase Induces Early Flowering in
      Arabidopsis thaliana.
AB  - N-acylethanolamines (NAEs) are bioactive lipids derived from the hydrolysis of
      the membrane phospholipid N-acylphosphatidylethanolamine (NAPE). In animal
      systems this reaction is part of the "endocannabinoid" signaling pathway, which
      regulates a variety of physiological processes. The signaling function of NAE is
      terminated by fatty acid amide hydrolase (FAAH), which hydrolyzes NAE to
      ethanolamine and free fatty acid. Our previous work in Arabidopsis thaliana
      showed that overexpression of AtFAAH (At5g64440) lowered endogenous levels of
      NAEs in seeds, consistent with its role in NAE signal termination. Reduced NAE
      levels were accompanied by an accelerated growth phenotype, increased sensitivity
      to abscisic acid (ABA), enhanced susceptibility to bacterial pathogens, and early
      flowering. Here we investigated the nature of the early flowering phenotype of
      AtFAAH overexpression. AtFAAH overexpressors flowered several days earlier than
      wild type and AtFAAH knockouts under both non-inductive short day (SD) and
      inductive long day (LD) conditions. Microarray analysis revealed that the
      FLOWERING LOCUS T (FT) gene, which plays a major role in regulating flowering
      time, and one target MADS box transcription factor, SEPATALLA3 (SEP3), were
      elevated in AtFAAH overexpressors. Furthermore, AtFAAH overexpressors, with the
      early flowering phenotype had lower endogenous NAE levels in leaves compared to
      wild type prior to flowering. Exogenous application of NAE 12:0, which was
      reduced by up to 30% in AtFAAH overexpressors, delayed the onset of flowering in
      wild type plants. We conclude that the early flowering phenotype of AtFAAH
      overexpressors is, in part, explained by elevated FT gene expression resulting
      from the enhanced NAE hydrolase activity of AtFAAH, suggesting that NAE
      metabolism may participate in floral signaling pathways.

PMID- 22645581
TI  - High affinity ammonium transporters: molecular mechanism of action.
AB  - The importance of the family of high affinity ammonium transporters is
      demonstrated by the presence of these proteins in all domains of life, including
      bacteria, archaea, fungi, plants, and humans. The majority of the proteins that
      have been studied from this family show high affinity and selectivity for
      ammonium, are impermeable to alkaline cations, saturate rapidly at low millimolar
      concentrations and most of them, are also permeable to methylammonium.
      Crystallization of homologue proteins from bacteria and archaea has demonstrated
      that the functional entity corresponds to a trimer, with each monomer maintaining
      a conductive pore. Through molecular modeling, it has been demonstrated that even
      though the identity of the proteins between bacteria/archaea with those from
      plants is below 25%, the latter seem to maintain similar tertiary and quaternary
      structures, an observation that has helped to address the functionality of
      conserved residues by means of mutational analysis. Results have shown that
      changes in the extracellular binding site of some plant transporters may result
      in their inhibition or reduction in transport activity, while in Escherichia
      coli, dissimilar replacements like Phe/Ala or Ser/Leu that eliminate possible pi
      interactions or H-bonds with ammonium, respectively, lead to more active
      transporters. Active mutants with changes in the pair of conserved His in the
      center of the transporter suggest these residues are dispensable. Additional
      mutations have identified other important amino acids, both in the entrance of
      the pore and in cytoplasmic loops. Regulation of this family of transporters can
      be achieved by interactions of the C-terminal with cytoplasmic loops within the
      same monomer, or with a neighbor in the trimer. Depending on the interacting
      residues, these contacts may lead to the activation or inhibition of the protein.
      The aim of this review is to critically evaluate the newest findings on the role
      of the proposed amino acids that structure the ammonium pathway, as well as
      highlight the importance of additional residues that have been identified through
      mutational analyses.

PMID- 22645582
TI  - Plant development, auxin, and the subsystem incompleteness theorem.
AB  - Plant morphogenesis (the process whereby form develops) requires signal cross
      talking among all levels of organization to coordinate the operation of metabolic
      and genomic subsystems operating in a larger network of subsystems. Each
      subsystem can be rendered as a logic circuit supervising the operation of one or
      more signal-activated system. This approach simplifies complex morphogenetic
      phenomena and allows for their aggregation into diagrams of progressively larger
      networks. This technique is illustrated here by rendering two logic circuits and
      signal-activated subsystems, one for auxin (IAA) polar/lateral intercellular
      transport and another for IAA-mediated cell wall loosening. For each of these
      phenomena, a circuit/subsystem diagram highlights missing components (either in
      the logic circuit or in the subsystem it supervises) that must be identified
      experimentally if each of these basic plant phenomena is to be fully understood.
      We also illustrate the "subsystem incompleteness theorem," which states that no
      subsystem is operationally self-sufficient. Indeed, a whole-organism perspective
      is required to understand even the most simple morphogenetic process, because,
      when isolated, every biological signal-activated subsystem is morphogenetically
      ineffective.

PMID- 22645583
TI  - Mobility of Transgenic Nucleic Acids and Proteins within Grafted Rootstocks for
      Agricultural Improvement.
AB  - Grafting has been used in agriculture for over 2000 years. Disease resistance and
      environmental tolerance are highly beneficial traits that can be provided through
      use of grafting, although the mechanisms, in particular for resistance, have
      frequently been unknown. As information emerges that describes plant disease
      resistance mechanisms, the proteins, and nucleic acids that play a critical role
      in disease management can be expressed in genetically engineered (GE) plant
      lines. Utilizing transgrafting, the combination of a GE rootstock with a wild
      type (WT) scion, or the reverse, has the potential to provide pest and pathogen
      resistance, impart biotic and abiotic stress tolerance, or increase plant vigor
      and productivity. Of central importance to these potential benefits is the
      question of to what extent nucleic acids and proteins are transmitted across a
      graft junction and whether the movement of these molecules will affect the
      efficacy of the transgrafting approach. Using a variety of specific examples,
      this review will report on the movement of organellar DNA, RNAs, and proteins
      across graft unions. Attention will be specifically drawn to the use of small
      RNAs and gene silencing within transgrafted plants, with a particular focus on
      pathogen resistance. The use of GE rootstocks or scions has the potential to
      extend the horticultural utility of grafting by combining this ancient technique
      with the molecular strategies of the modern era.

PMID- 22645584
TI  - The physical chemistry of the enigmatic phospholipid diacylglycerol
      pyrophosphate.
AB  - Phosphatidic acid (PA) is a lipid second messenger that is formed transiently in
      plants in response to different stress conditions, and plays a role in recruiting
      protein targets, ultimately enabling an adequate response. Intriguingly, this
      increase in PA concentration in plants is generally followed by an increase in
      the phospholipid diacylglycerolpyrophosphate (DGPP), via turnover of PA. Although
      DGPP has been shown to induce stress-related responses in plants, it is unclear
      to date what its molecular function is and how it exerts its effect. Here, we
      describe the physicochemical properties, i.e., effective molecular shape and
      charge, of DGPP. We find that unlike PA, which imparts a negative curvature
      stress to a (phospho)lipid bilayer, DGPP stabilizes the bilayer phase of
      phosphatidylethanolamine (PE), similar to the effect of phosphatidylcholine (PC).
      DGPP thus has zero curvature. The pKa(2) of the phosphomonoester of DGPP is 7.44
      +/- 0.02 in a PC bilayer, compared to a pKa(2) of 7.9 for PA. Replacement of half
      of the PC with PE decreases the pKa(2) of DGPP to 6.71 +/- 0.02, similar to the
      behavior previously described for PA and summarized in the electrostatic-hydrogen
      bond switch model. Implications for the potential function of DGPP in
      biomembranes are discussed.

PMID- 22645585
TI  - Oxylipin Signaling: A Distinct Role for the Jasmonic Acid Precursor cis-(+)-12
      Oxo-Phytodienoic Acid (cis-OPDA).
AB  - Oxylipins are lipid-derived compounds, many of which act as signals in the plant
      response to biotic and abiotic stress. They include the phytohormone jasmonic
      acid (JA) and related jasmonate metabolites cis-(+)-12-oxo-phytodienoic acid (cis
      OPDA), methyl jasmonate, and jasmonoyl-L-isoleucine (JA-Ile). Besides the defense
      response, jasmonates are involved in plant growth and development and regulate a
      range of processes including glandular trichome development, reproduction, root
      growth, and senescence. cis-OPDA is known to possess a signaling role distinct
      from JA-Ile. The non-enzymatically derived phytoprostanes are structurally
      similar to cis-OPDA and induce a common set of genes that are not responsive to
      JA in Arabidopsis thaliana. A novel role for cis-OPDA in seed germination
      regulation has recently been uncovered based on evidence from double mutants and
      feeding experiments showing that cis-OPDA interacts with abscisic acid (ABA),
      inhibits seed germination, and increases ABA INSENSITIVE5 (ABI5) protein
      abundance. Large amounts of cis-OPDA are esterified to galactolipids in A.
      thaliana and the resulting compounds, known as Arabidopsides, are thought to act
      as a rapidly available source of cis-OPDA.

PMID- 22645587
TI  - Mass spectrometry for characterizing plant cell wall polysaccharides.
AB  - Mass spectrometry is a selective and powerful technique to obtain identification
      and structural information on compounds present in complex mixtures. Since it
      requires only small sample amount it is an excellent tool for researchers
      interested in detecting changes in composition of complex carbohydrates of
      plants. This mini-review gives an overview of common mass spectrometry techniques
      applied to the analysis of plant cell wall carbohydrates. It presents examples in
      which mass spectrometry has been used to elucidate the structure of
      oligosaccharides derived from hemicelluloses and pectins and illustrates how
      information on sequence, linkages, branching, and modifications are obtained from
      characteristic fragmentation patterns.

PMID- 22645586
TI  - Leveraging proteomics to understand plant-microbe interactions.
AB  - Understanding the interactions of plants with beneficial and pathogenic microbes
      is a promising avenue to improve crop productivity and agriculture
      sustainability. Proteomic techniques provide a unique angle to describe these
      intricate interactions and test hypotheses. The various approaches for proteomic
      analysis generally include protein/peptide separation and identification, but can
      also provide quantification and the characterization of post-translational
      modifications. In this review, we discuss how these techniques have been applied
      to the study of plant-microbe interactions. We also present some areas where this
      field of study would benefit from the utilization of newly developed methods that
      overcome previous limitations. Finally, we reinforce the need for expanding,
      integrating, and curating protein databases, as well as the benefits of combining
      protein-level datasets with those from genetic analyses and other high-throughput
      large-scale approaches for a systems-level view of plant-microbe interactions.

PMID- 22645588
TI  - Does a similar metabolic reprogramming occur in fe-deficient plant cells and
      animal tumor cells?

PMID- 22645589
TI  - A role for phosphoinositides in regulating plant nuclear functions.
AB  - Nuclear localized inositol phospholipids and inositol phosphates are important
      for regulating many essential processes in animal and yeast cells such as DNA
      replication, recombination, RNA processing, mRNA export and cell cycle
      progression. An overview of the current literature indicates the presence of a
      plant nuclear phosphoinositide (PI) pathway. Inositol phospholipids, inositol
      phosphates, and enzymes of the PI pathway have been identified in plant nuclei
      and are implicated in DNA replication, chromatin remodeling, stress responses and
      hormone signaling. In this review, the potential functions of the nuclear PI
      pathway in plants are discussed within the context of the animal and yeast
      literature. It is anticipated that future research will help shed light on the
      functional significance of the nuclear PI pathway in plants.

PMID- 22645591
TI  - Ion induced changes in the structure of bordered pit membranes.
AB  - Ion-mediated changes in xylem hydraulic resistance are hypothesized to result
      from hydrogel like properties of pectins located in the bordered pit membranes
      separating adjacent xylem vessels. Although the kinetics of the ion-mediated
      changes in hydraulic resistance are consistent with the swelling/deswelling
      behavior of pectins, there is no direct evidence of this activity. In this report
      we use atomic force microscopy (AFM) to investigate structural changes in
      bordered pit membranes associated with changes in the ionic concentration of the
      surrounding solution. When submerged in de-ionized water, AFM revealed bordered
      pit membranes as relatively smooth, soft, and lacking any sharp edges surface, in
      contrast to pictures from scanning electron microscope (SEM) or AFM performed on
      air-dry material. Exposure of the bordered pit membranes to 50 mM KCl solution
      resulted in significant changes in both surface physical properties and elevation
      features. Specifically, bordered pit membranes became harder and the fiber edges
      were clearly visible. In addition, the membrane contracted and appeared much
      rougher due to exposed microfibers. In neither solution was there any evidence of
      discrete pores through the membrane whose dimensions were altered in response to
      the ionic composition of the surrounding solution. Instead the variable hydraulic
      resistance appears to involve changes in the both the permeability and the
      thickness of the pit membrane.

PMID- 22645590
TI  - Traversing the Cell: Agrobacterium T-DNA's Journey to the Host Genome.
AB  - The genus Agrobacterium is unique in its ability to conduct interkingdom genetic
      exchange. Virulent Agrobacterium strains transfer single-strand forms of T-DNA (T
      strands) and several Virulence effector proteins through a bacterial type IV
      secretion system into plant host cells. T-strands must traverse the plant wall
      and plasma membrane, traffic through the cytoplasm, enter the nucleus, and
      ultimately target host chromatin for stable integration. Because any DNA sequence
      placed between T-DNA "borders" can be transferred to plants and integrated into
      the plant genome, the transfer and intracellular trafficking processes must be
      mediated by bacterial and host proteins that form complexes with T-strands. This
      review summarizes current knowledge of proteins that interact with T-strands in
      the plant cell, and discusses several models of T-complex (T-strand and
      associated proteins) trafficking. A detailed understanding of how these
      macromolecular complexes enter the host cell and traverse the plant cytoplasm
      will require development of novel technologies to follow molecules from their
      bacterial site of synthesis into the plant cell, and how these transferred
      molecules interact with host proteins and sub-cellular structures within the host
      cytoplasm and nucleus.

PMID- 22645592
TI  - Benzalacetone synthase.
AB  - Benzalacetone synthase, from the medicinal plant Rheum palmatum (RpBAS), is a
      plant-specific chalcone synthase (CHS) superfamily of type III polyketide
      synthase (PKS). RpBAS catalyzes the one-step, decarboxylative condensation of 4
      coumaroyl-CoA with malonyl-CoA to produce the C(6)-C(4) benzalacetone scaffold.
      The X-ray crystal structures of RpBAS confirmed that the diketide-forming
      activity is attributable to the characteristic substitution of the conserved
      active-site "gatekeeper" Phe with Leu. Furthermore, the crystal structures
      suggested that RpBAS employs novel catalytic machinery for the thioester bond
      cleavage of the enzyme-bound diketide intermediate and the final decarboxylation
      reaction to produce benzalacetone. Finally, by exploiting the remarkable
      substrate tolerance and catalytic versatility of RpBAS, precursor-directed
      biosynthesis efficiently generated chemically and structurally divergent,
      unnatural novel polyketide scaffolds. These findings provided a structural basis
      for the functional diversity of the type III PKS enzymes.

PMID- 22645593
TI  - Grand challenges in plant biotechnology.

PMID- 22645594
TI  - Arabidopsis Seed Coat Mucilage is a Specialized Cell Wall that Can be Used as a
      Model for Genetic Analysis of Plant Cell Wall Structure and Function.
AB  - Arabidopsis seed coat epidermal cells produce a large quantity of mucilage that
      is extruded upon exposure to water. Chemical analyses and cell biological
      techniques suggest that this mucilage represents a specialized type of secondary
      cell wall composed primarily of pectin with lesser amounts of cellulose and
      xyloglucan. Once extruded, the mucilage capsule has a distinctive structure with
      an outer non-adherent layer that is easily removed by shaking in water, and an
      inner adherent layer that can only be removed with strong acid or base. Most of
      the cellulose in the mucilage is present in the inner layer and is responsible at
      least in part for its adherence to the seed. There are also differences in the
      pectin composition between the two layers that could contribute to the difference
      in adherence. The Arabidopsis seed coat epidermis and its mucilage are not
      essential for seed viability or germination. This dispensability, combined with
      the fact that the epidermal cells synthesize an accessible pectin-rich cell wall
      at a specific time in development, makes them well suited as a genetic model for
      studying cell wall biogenesis, function, and regulation. Mutants defective in
      seed mucilage identified by both forward and reverse genetic analyses are proving
      useful in establishing connections between carbohydrate structure and cell wall
      properties in vivo. In the future, genetic engineering of seed coat mucilage
      carbohydrates should prove useful for testing hypotheses concerning cell wall
      structure and function.

PMID- 22645595
TI  - Dynamic Light Regulation of Translation Status in Arabidopsis thaliana.
AB  - Light, a dynamic environmental parameter, is an essential regulator of plant
      growth and development. Light-regulated transcriptional networks are well
      documented, whereas light-regulated post-transcriptional regulation has received
      limited attention. In this study, dynamics in translation of cytosolic mRNAs were
      evaluated at the genome-level in Arabidopsis thaliana seedlings grown under a
      typical light/dark diurnal regime, shifted to darkness at midday, and then re
      illuminated. One-hour of unanticipated darkness reduced levels of polysomes by
      17% in a manner consistent with inhibition of initiation of translation. This
      down-regulation of translation was reversed within 10 min of re-illumination.
      Quantitative comparison of the total cellular population of transcripts (the
      transcriptome) to those associated with one or more 80S ribosome (the
      translatome) identified over 1600 mRNAs that were differentially translated in
      response to light availability. Unanticipated darkness limited both transcription
      and translation of mRNAs encoding components of the photosynthetic machinery.
      Many mRNAs encoding proteins associated with the energy demanding process of
      protein synthesis were stable but sequestered in the dark, in a rapidly
      reversible manner. A meta-analysis determined these same transcripts were
      similarly and coordinately regulated in response to changes in oxygen
      availability. The dark and hypoxia translationally repressed mRNAs lack highly
      supported candidate RNA-regulatory elements but are characterized by G + C-rich
      5'-untranslated regions. We propose that modulation of translation of a subset of
      cellular mRNAs functions as an energy conservation mechanism.

PMID- 22645596
TI  - Endoplasmic reticulum-associated degradation of glycoproteins in plants.
AB  - In all eukaryotes the endoplasmic reticulum (ER) has a central role in protein
      folding and maturation of secretory and membrane proteins. Upon translocation
      into the ER polypeptides are immediately subjected to folding and modifications
      involving the formation of disulfide bridges, assembly of subunits to multi
      protein complexes, and glycosylation. During these processes incompletely folded,
      terminally misfolded, and unassembled proteins can accumulate which endanger the
      cellular homeostasis and subsequently the survival of cells and tissues.
      Consequently, organisms have developed a quality control system to cope with this
      problem and remove the unwanted protein load from the ER by a process
      collectively referred to as ER-associated degradation (ERAD) pathway. Recent
      studies in Arabidopsis have identified plant ERAD components involved in the
      degradation of aberrant proteins and evidence was provided for a specific role in
      abiotic stress tolerance. In this short review we discuss our current knowledge
      about this important cellular pathway.

PMID- 22645597
TI  - Effects of four different restoration treatments on the natural abundance of
      (15)n stable isotopes in plants.
AB  - delta(15)N signals in plant and soil material integrate over a number of
      biogeochemical processes related to nitrogen (N) and therefore provide
      information on net effects of multiple processes on N dynamics. In general little
      is known in many grassland restoration projects on soil-plant N dynamics in
      relation to the restoration treatments. In particular, delta(15)N signals may be
      a useful tool to assess whether abiotic restoration treatments have produced the
      desired result. In this study we used the range of abiotic and biotic conditions
      provided by a restoration experiment to assess to whether the restoration
      treatments and/or plant functional identity and legume neighborhood affected
      plant delta(15)N signals. The restoration treatments consisted of hay transfer
      and topsoil removal, thus representing increasing restoration effort, from no
      restoration measures, through biotic manipulation to major abiotic manipulation.
      We measured delta(15)N and %N in six different plant species (two non-legumes and
      four legumes) across the restoration treatments. We found that restoration
      treatments were clearly reflected in delta(15)N of the non-legume species, with
      very depleted delta(15)N associated with low soil N, and our results suggest this
      may be linked to uptake of ammonium (rather than nitrate). The two non-legume
      species differed considerably in their delta(15)N signals, which may be related
      to the two species forming different kinds of mycorrhizal symbioses. Plant
      delta(15)N signals could clearly separate legumes from non-legumes, but our
      results did not allow for an assessment of legume neighborhood effects on non
      legume delta(15)N signals. We discuss our results in the light of what the
      delta(15)N signals may be telling us about plant-soil N dynamics and their
      potential value as an indicator for N dynamics in restoration.

PMID- 22645598
TI  - The ER/Golgi Interface - Is There Anything in-between?

PMID- 22645599
TI  - Co-expression of cell-wall related genes: new tools and insights.
AB  - Global transcript analyses based on publicly available microarray dataset have
      revealed that genes with similar function tend to be transcriptionally
      coordinated. Indeed, many genes involved in the formation of cellulose,
      hemicelluloses, and lignin have been identified using co-expression approaches in
      Arabidopsis. To facilitate these transcript analyses, several web-based tools
      have been developed that allow researchers to investigate co-expression
      relationships of their gene(s) of interest. In addition, several tools now also
      provide the possibility of comparative transcriptional analyses across species,
      which potentially increases the predictive power. In this short review, we
      describe recent developments and updates of plant-related co-expression tools,
      and summarize studies that have successfully used expression profiling in cell
      wall research. Finally, we illustrate the value of comparative co-expression
      relationships across species using genes involved in lignin biosynthesis.

PMID- 22645600
TI  - RiceRBP: A Resource for Experimentally Identified RNA Binding Proteins in Oryza
      sativa.
AB  - RNA binding proteins (RBPs) play an important role not only in nuclear gene
      expression, but also in cytosolic events, including RNA transport, localization,
      translation, and stability. Although over 200 RBPs are predicted from the
      Arabidopsis genome alone, relatively little is known about these proteins in
      plants as many exhibit no homology to known RBPs in other eukaryotes.
      Furthermore, RBPs likely have low expression levels making them difficult to
      identify and study. As part of our continuing efforts to understand plant
      cytosolic gene expression and the factors involved, we employed a combination of
      affinity chromatography and proteomic techniques to enrich for low abundance RBPs
      in developing rice seed. Our results have been compiled into RiceRBP
      (http://www.bioinformatics2.wsu.edu/RiceRBP), a database that contains 257
      experimentally identified proteins, many of which have not previously been
      predicted to be RBPs. For each of the identified proteins, RiceRBP provides
      information on transcript and protein sequence, predicted protein domains,
      details of the experimental identification, and whether antibodies have been
      generated for public use. In addition, tools are available to analyze expression
      patterns for the identified genes, view phylogentic relationships and search for
      orthologous proteins. RiceRBP is a valuable tool for the community in the study
      of plant RBPs.

PMID- 22645601
TI  - Hepatic Cerebroside Sulfotransferase Is Induced by PPARalpha Activation in Mice.
AB  - Sulfatides are one of the major sphingoglycolipids in mammalian serum and are
      synthesized and secreted mainly from the liver as a component of lipoproteins.
      Recent studies revealed a protective role for serum sulfatides against
      arteriosclerosis and hypercoagulation. Although peroxisome proliferator-activated
      receptor (PPAR) alpha has important functions in hepatic lipoprotein metabolism,
      its association with sulfatides has not been investigated. In this study,
      sulfatide levels and the expression of enzymes related to sulfatide metabolism
      were examined using wild-type (+/+), Ppara-heterozygous (+/-), and Ppara-null (-/
      ) mice given a control diet or one containing 0.1% fenofibrate, a clinically used
      hypolipidemic drug and PPARalpha activator. Fenofibrate treatment increased serum
      and hepatic sulfatides in Ppara (+/+) and (+/-) mice through a marked induction
      of hepatic cerebroside sulfotransferase (CST), a key enzyme in sulfatide
      synthesis, in a PPARalpha-dependent manner. Furthermore, increases in CST mRNA
      levels were correlated with mRNA elevations of several known PPARalpha target
      genes, and such changes were not observed for other sulfatide-metabolism enzymes
      in the liver. These results suggest that PPARalpha activation enhances hepatic
      sulfatide synthesis via CST induction and implicate CST as a novel PPARalpha
      target gene.

PMID- 22645602
TI  - Prevention of diabetic complications by activation of Nrf2: diabetic
      cardiomyopathy and nephropathy.
AB  - Diabetic cardiomyopathy and nephropathy are two major causes of death of patients
      with diabetes. Extra generation of reactive oxygen species (ROS), induced by
      hyperglycemia, is considered as the main reason for the development of these
      diabetic complications. Transcription factor, NFE2-related factor 2 (Nrf2), is a
      master regulator of cellular detoxification response and redox status, and also
      provides a protective action from various oxidative stresses and damages.
      Recently we have demonstrated its important role in determining the
      susceptibility of cells or tissues to diabetes-induced oxidative stress and/or
      damage. Therefore, this review will specifically summarize the information
      available regarding the effect of Nrf2 on the diabetic complications with a focus
      on diabetic cardiomyopathy and nephropathy. Given the feature that Nrf2 is easily
      induced by several compounds, we also discussed the role of different Nrf2
      activators in the prevention or therapy of various diabetic complications. These
      findings suggest that Nrf2 has a potential application in the clinic setting for
      diabetic patients in the short future.

PMID- 22645603
TI  - Increased oxidative stress and imbalance in antioxidant enzymes in the brains of
      alloxan-induced diabetic rats.
AB  - Diabetes Mellitus (DM) is associated with pathological changes in the central
      nervous system (SNC) as well as alterations in oxidative stress. Thus, the main
      objective of this study was to evaluate the effects of the animal model of
      diabetes induced by alloxan on memory and oxidative stress. Diabetes was induced
      in Wistar rats by using a single injection of alloxan (150 mg/kg), and fifteen
      days after induction, the rats memory was evaluated through the use of the object
      recognition task. The oxidative stress parameters and the activity of antioxidant
      enzymes, superoxide dismutase (SOD), and catalase (CAT) were measured in the rat
      brain. The results showed that diabetic rats did not have alterations in their
      recognition memory. However, the results did show that diabetic rats had
      increases in the levels of superoxide in the prefrontal cortex, and in
      thiobarbituric acid reactive species (TBARS) production in the prefrontal cortex
      and in the amygdala in submitochondrial particles. Also, there was an increase in
      protein oxidation in the hippocampus and striatum, and in TBARS oxidation in the
      striatum and amygdala. The SOD activity was decreased in diabetic rats in the
      striatum and amygdala. However, the CAT activity was increased in the hippocampus
      taken from diabetic rats. In conclusion, our findings illustrate that the animal
      model of diabetes induced by alloxan did not cause alterations in the animals'
      recognition memory, but it produced oxidants and an imbalance between SOD and CAT
      activities, which could contribute to the pathophysiology of diabetes.

PMID- 22645604
TI  - Mannan-binding lectin in diabetic kidney disease: the impact of mouse genetics in
      a type 1 diabetes model.
AB  - BACKGROUND. Mannan-binding lectin (MBL) is involved in the development of
      diabetic nephropathy. MBL is a part of the innate immune system where it can
      activate the complement system. Serum MBL level predicts later renal impairment
      in diabetes patients. Direct involvement of MBL in the development of diabetic
      kidney disease is observed in one animal strain. However, this involvement may
      differ among the animal strains. We thus examined the impact of the genetic
      background on the role of MBL in diabetic nephropathy. MATERIALS/METHODS:
      C57BL/6JBomTac and 129S6/SvEvTac mice were compared. In both strains,
      experimental type 1 diabetes was induced in wild-type (WT) and MBL-knockout (MBL
      KO) mice by streptozotocin. Nondiabetic WT and MBL-KO mice were used as controls.
      We tested if MBL modified the diabetes-induced kidney changes by two-way ANOVA
      allowing for interaction. RESULTS: MBL aggravated diabetes-induced kidney growth
      and glomerulus enlargement in C57BL/6JBomTac mice. MBL did not modify diabetes
      effects on glomerular basement membrane thickness or mesangial volume in any
      strain. Diabetes-induced changes in renal gene transcription of growth factors
      and matrix components were unaffected by MBL. CONCLUSIONS: Strain-specific MBL
      effects were found on downstream diabetic kidney changes. This emphasizes the
      importance of genetic background in this model of diabetic complications.

PMID- 22645605
TI  - Prevention of Peritoneal Metastases from Colon Cancer in High-Risk Patients:
      Preliminary Results of Surgery plus Prophylactic HIPEC.
AB  - The study compared the outcome in patients with advanced colonic cancer at high
      risk of peritoneal metastases (mucinous or signet-ring cell) without peritoneal
      or systemic spread, treated with standard colectomy or a more aggressive combined
      surgical approach. The study included patients with colonic cancer with clinical
      T3/T4, any N, M0, and mucinous or signet ring cell histology. The 25 patients in
      the experimental group underwent hemicolectomy, omentectomy, bilateral
      adnexectomy, hepatic round ligament resection, and appendectomy, followed by
      HIPEC. The control group comprised 50 patients treated with standard surgical
      resection during the same period in the same hospital by different surgical
      teams. Outcome data, morbidity, peritoneal recurrence rate, and overall, and
      disease-free survival, were compared. Peritoneal recurrence developed in 4% of
      patients in the experimental group and 22% of controls without increasing
      morbidity (P < 0.05). Actuarial overall survival curves disclosed no significant
      differences, whereas actuarial disease-free survival curves showed a significant
      difference between groups (36.8 versus 21.9 months, P < 0.01). A more aggressive
      preventive surgical approach combined with HIPEC reduces the incidence of
      peritoneal recurrence in patients with advanced mucinous colonic cancer and also
      significantly increases disease-free survival compared with a homogeneous control
      group treated with a standard surgical approach without increasing morbidity.

PMID- 22645606
TI  - Advancements in laparoscopic partial nephrectomy: expanding the feasibility of
      nephron-sparing.
AB  - Partial nephrectomy (PN) offers equivalent oncologic outcomes to radical
      nephrectomy (RN) but has greater preservation of renal function and less risk of
      chronic kidney disease and cardiovascular disease. Laparoscopic PN remains
      underutilized likely because it is a technically challenging operation with
      higher rates of perioperative complications compared to open PN and laparoscopic
      RN. A review of the latest PN literature demonstrates that recent advancements in
      laparoscopic approaches, imaging modalities, ischemic mitigating strategies,
      renorrhaphy techniques, and hemostatic agents will likely allow greater
      utilization of LPN and expand its usage to increasingly more complex tumors.

PMID- 22645608
TI  - Nutrition in severe dementia.
AB  - An increasing proportion of older adults with Alzheimer's disease or other
      dementias are now surviving to more advanced stages of the illness. Advanced
      dementia is associated with feeding problems, including difficulty in swallowing
      and respiratory diseases. Patients become incompetent to make decisions. As a
      result, complex situations may arise in which physicians and families decide
      whether artificial nutrition and hydration (ANH) is likely to be beneficial for
      the patient. The objective of this paper is to present methods for evaluating the
      nutritional status of patients with severe dementia as well as measures for the
      treatment of nutritional disorders, the use of vitamin and mineral
      supplementation, and indications for ANH and pharmacological therapy.

PMID- 22645607
TI  - Surveillance and treatment of non-muscle-invasive bladder cancer in the USA.
AB  - Seventy percent of newly diagnosed bladder cancers are classified as non-muscle
      invasive bladder cancer (NMIBC) and are often associated with high rates of
      recurrence that require lifelong surveillance. Currently available treatment
      options for NMIBC are associated with toxicities that limit their use, and actual
      practice patterns vary depending upon physician and patient characteristics. In
      addition, bladder cancer has a high economic and humanistic burden in the United
      States (US) population and has been cited as one of the most costly cancers to
      treat. An unmet need exists for new treatment options associated with fewer
      complications, better patient compliance, and decreased healthcare costs.
      Increased prevention of recurrence through greater adherence to evidence-based
      guidelines and the development of novel therapies could therefore result in
      substantial savings to the healthcare system.

PMID- 22645609
TI  - Ion channels and zinc: mechanisms of neurotoxicity and neurodegeneration.
AB  - Ionotropic glutamate receptors, such as NMDA, AMPA and kainate receptors, are
      ligand-gated ion channels that mediate much of the excitatory neurotransmission
      in the brain. Not only do these receptors bind glutamate, but they are also
      regulated by and facilitate the postsynaptic uptake of the trace metal zinc. This
      paper discusses the role of the excitotoxic influx and accumulation of zinc, the
      mechanisms responsible for its cytotoxicity, and a number of disorders of the
      central nervous system that have been linked to these neuronal ion channels and
      zinc toxicity including ischemic brain injury, traumatic brain injury, and
      epilepsy.

PMID- 22645610
TI  - Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT-Part II:
      Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment.
AB  - Recently, a variety of physiologically based pharmacokinetic (PBPK) models have
      been developed for the essential element manganese. This paper reviews the
      development of PBPK models (e.g., adult, pregnant, lactating, and neonatal rats,
      nonhuman primates, and adult, pregnant, lactating, and neonatal humans) and
      relevant risk assessment applications. Each PBPK model incorporates critical
      features including dose-dependent saturable tissue capacities and asymmetrical
      diffusional flux of manganese into brain and other tissues. Varied influx and
      efflux diffusion rate and binding constants for different brain regions account
      for the differential increases in regional brain manganese concentrations
      observed experimentally. We also present novel PBPK simulations to predict
      manganese tissue concentrations in fetal, neonatal, pregnant, or aged
      individuals, as well as individuals with liver disease or chronic manganese
      inhalation. The results of these simulations could help guide risk assessors in
      the application of uncertainty factors as they establish exposure guidelines for
      the general public or workers.

PMID- 22645611
TI  - Methylation-mediated molecular dysregulation in clinical oral malignancy.
AB  - Herein we provide a concise review of the state of methylation research as it
      pertains to clinical oral cancerous and precancerous tissues. We provide context
      for ongoing research efforts in this field and describe technologies that are
      presently being applied to analyze clinical specimens. We also discuss the
      various recurrent methylation changes that have been reported for oral malignancy
      (including those genes frequently silenced by promoter methylation and the small
      RNAs with activity modulated by methylation changes) and describe surrogate
      disease markers identified via epigenetic analysis of saliva and blood specimens
      from patients with oral cancer.

PMID- 22645612
TI  - Advancements in the Treatment of Metastatic Breast Cancer (MBC): The Role of
      Ixabepilone.
AB  - Successful management of breast cancer in the metastatic setting is often
      confounded by resistance to chemotherapeutics, in particular anthracyclines and
      taxanes. The limited number of effective treatment options for patients with more
      aggressive biological subtypes, such as triple-negative metastatic breast cancer,
      is especially concerning. As such, a therapy clinically proven to be effective in
      this subtype would be of great value. Ixabepilone, a novel synthetic lactam
      analog of epothilone B, demonstrated better clinical outcomes in metastatic
      disease, particularly in triple-negative breast cancer. Most recently, studies
      have shown the activity of ixabepilone in the neoadjuvant setting, suggesting a
      role for this drug in primary disease. Notably, treating in the neoadjuvant
      setting might allow clinicians to explore the predictive value of biomarkers and
      response to treatment, as pharmacogenomic approaches to therapy continue to
      evolve. In this article, we review the efficacy and safety data of ixabepilone as
      a monotherapy and as a component of combination therapy for metastatic and
      primary breast cancer.

PMID- 22645614
TI  - Cardiovascular risk in patients with psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis.
      In addition to skin and joint involvement, there is increasing evidence
      suggesting that patients with PsA also have an increase in risk of clinical and
      subclinical cardiovascular diseases, mostly due to accelerating atherosclerosis.
      Both conventional and nonconventional cardiovascular risk factors contribute to
      the increased cardiovascular risk in PsA. Chronic inflammation plays a pivotal
      role in the pathogenesis of atherosclerosis in PsA, acting independently and/or
      synergistically with the conventional risk factors. In this paper, we discuss the
      current literature indicating that patients with PsA are at risk of
      cardiovascular diseases.

PMID- 22645615
TI  - Placental Pathology and Blood Pressure's Level in Women with Hypertensive
      Disorders in Pregnancy.
AB  - Objective. The aim of this study was to investigate the extent of placental
      lesions associated with blood pressure (BP) levels in pregnancies complicated by
      hypertension. Methods. 55 singleton pregnancies complicated by mild hypertension
      were recruited and compared to 55 pregnancies complicated by severe hypertension.
      The histological assessment was carried out with regard to the following aspects:
      vessels number/field of vision, infarction, villous fibrinoid necrosis, villous
      hypermaturity, avascular villi, calcifications, lymphohistiocytic villitis, and
      thickened vessels. Statistical analysis was performed by SPSS. Results. All
      placental lesions were observed more often in the severe hypertension group.
      Vessels number was significantly decreased, and infarction and villous fibrinoid
      necrosis were significantly increased in the placentas of the severe hypertension
      group compared to the mild hypertension group (P < 0.001). Conclusion. This study
      supports that the extent of placental lesions in hypertensive pregnancies is
      correlated with hypertension level and so highlights blood pressure level as a
      mirror of placental function.

PMID- 22645613
TI  - Epigenetic dysregulation in laryngeal squamous cell carcinoma.
AB  - Laryngeal carcinoma is a common head and neck cancer with poor prognosis.
      Patients with laryngeal carcinoma usually present late leading to the reduced
      treatment efficacy and high rate of recurrence. Despite the advance in the use of
      molecular markers for monitoring human cancers in the past decades, there are
      still no reliable markers for use to screen laryngeal carcinoma and follow the
      patients after treatment. Epigenetics emerged as an important field in
      understanding the biology of the human malignancies. Epigenetic alterations refer
      to the dysregulation of gene, which do not involve the alterations of the DNA
      sequence. Major epigenetic changes including methylation imbalance, histone
      modification, and small RNA dysregulation could play a role in the development of
      human malignancies. Global epigenetic change is now regarded as a molecular
      signature of cancer. The characteristics and behavior of a cancer could be
      predicted based on the specific epigenetic pattern. We here provide a review on
      the understanding of epigenetic dysregulation in laryngeal carcinoma. Further
      knowledge on the initiation and progression of laryngeal carcinoma at epigenetic
      level could promote the translation of the knowledge to clinical use.

PMID- 22645616
TI  - Epidemiology, etiology, diagnosis, and management of placenta accreta.
AB  - Placenta accreta is a severe pregnancy complication and is currently the most
      common indication for peripartum hysterectomy. It is becoming an increasingly
      common complication mainly due to the increasing rate of cesarean delivery. Main
      risk factor for placenta accreta is a previous cesarean delivery particularly
      when accompanied with a coexisting placenta previa. Antenatal diagnosis seems to
      be a key factor in optimizing maternal outcome. Diagnosis can be achieved by
      ultrasound in the majority of cases. Women with placenta accreta are usually
      delivered by a cesarean section. In order to avoid an emergency cesarean and to
      minimize complications of prematurity it is acceptable to schedule cesarean at 34
      to 35 weeks. A multidisciplinary team approach and delivery at a center with
      adequate resources, including those for massive transfusion are both essential to
      reduce neonatal and maternal morbidity and mortality. The optimal management
      after delivery of the neonate is vague since randomized controlled trials and
      large cohort studies are lacking. Cesarean hysterectomy is probably the
      preferable treatment. In carefully selected cases, when fertility is desired,
      conservative management may be considered with caution. The current review
      discusses the epidemiology, predisposing factors, pathogenesis, diagnostic
      methods, clinical implications and management options of this condition.

PMID- 22645617
TI  - A five-year followup of human seminal plasma allergy in an 18-year-old woman.
AB  - Case reports of women with the rare condition of human seminal plasma allergy
      have indicated that the condition may be associated with life-threatening
      anaphylactic reactions in relation to coitus. Few observations, if any, of long
      term outcome of the condition are available. The aim of this paper was to present
      a case diagnosed in an 18-year-old girl who presented with generalized urticaria,
      nasal congestion and secretion, conjunctivitis, and periorbital and labial oedema
      6-8 hours after coitus. During five years of followup the condition improved
      clinically significantly. Due to intimacy concerns and the low prevalence of the
      condition robust long term data on the natural course of the condition are
      difficult to obtain. The present case suggests that in some patients the
      condition may improve over time.

PMID- 22645618
TI  - Mutation in the Prothrombin Gene G20210A as a Cause of Cerebral Venous
      Thrombosis.
AB  - Introduction. Cerebral venous sinus thrombosis (CVST) is a rare form of
      cerebrovascular disease, which may manifest clinically by a wide variety of signs
      and symptoms. It has been associated with multiple risk factors including genetic
      or acquired blood disorders, infections, and trauma. Case Report. Man of 17 years
      who presented with 10 days of intense global headache with nausea and vomiting
      and subsequent onset of mild hemiparesis and hypoesthesia in right hemibody.
      Studies show venous thrombosis of the superior longitudinal sinus. It was
      identified a gene mutation in prothrombin G20210A as a probable cause of the
      thrombosis. Conclusions. Substitution of guanine for adenine at nucleotide 20210
      in the coding region of the prothrombin gene is the second most common primary
      thrombophilia. Multiple cases of CVST have been associated with this mutation. In
      the presence of CVST must be considered the primary studies for thrombophilia
      gene mutations, including prothrombin G20210A.

PMID- 22645620
TI  - Promoting appropriate use of drugs in children.
AB  - Promotion of appropriate and safe drugs in children is the need of the hour
      globally. Pediatric population by itself is a spectrum of different physiologies
      with significant variation in pharmacodynamics and pharmacokinetics.
      Unfortunately, 50-90% of drugs used in children today have never been actually
      studied in this population, and the results of drug studies done in adults are
      often extrapolated for use in children. Many medicines in pediatrics are off
      label or unlicensed. There is a spurt in drug resistance due to the overzealous
      prescription of antimicrobials not indicated, such as, using inadequate dosage or
      duration of drug regime leading to partially treated infections, using the wrong
      antimicrobial due to ignorance of causative organism, and finally using
      indigenous, irrational combinations. Availability of properly labeled and safe
      pediatric formulations, regular audit by pharmacists, judicious prescriptions,
      proper counseling about drug administration, surveillance of adverse effects, and
      pediatric drug trials can be the best possible interventions to offer appropriate
      medicines to children and thereby save millions of lives.

PMID- 22645619
TI  - Ex vivo expansion of human mesenchymal stem cells in defined serum-free media.
AB  - Human mesenchymal stem cells (hMSCs) are presently being evaluated for their
      therapeutic potential in clinical studies to treat various diseases, disorders,
      and injuries. To date, early-phase studies have indicated that the use of both
      autologous and allogeneic hMSCs appear to be safe; however, efficacy has not been
      demonstrated in recent late-stage clinical trials. Optimized cell bioprocessing
      protocols may enhance the efficacy as well as safety of hMSC therapeutics.
      Classical media used for generating hMSCs are typically supplemented with ill
      defined supplements such as fetal bovine serum (FBS) or human-sourced
      alternatives. Ideally, culture media are desired to have well-defined serum-free
      formulations that support the efficient production of hMSCs while maintaining
      their therapeutic and differentiation capacity. Towards this objective, we review
      here current cell culture media for hMSCs and discuss medium development
      strategies.

PMID- 22645621
TI  - Cigarette design features in low-, middle-, and high-income countries.
AB  - Previous studies have shown that country income grouping is correlated with
      cigarette engineering. Cigarettes (N = 111 brands) were purchased during 2008
      2010 from 11 low-, middle-, and high-income countries to assess physical
      dimensions and an array of cigarette design features. Mean ventilation varied
      significantly across low- (7.5%), middle- (15.3%), and high-income (26.2%)
      countries (P <= 0.001). Differences across income groups were also seen in
      cigarette length (P = 0.001), length of the tipping paper (P = 0.01), filter
      weight (P = 0.017), number of vent rows (P = 0.003), per-cigarette tobacco weight
      (P = 0.04), and paper porosity (P = 0.008). Stepwise linear regression showed
      ventilation and tobacco length as major predictors of ISO tar yields in low
      income countries (P = 0.909, 0.047), while tipping paper (P < 0.001), filter
      length (P < 0.001), number of vent rows (P = 0.014), and per-cigarette weight (P
      = 0.015) were predictors of tar yields in middle-income countries. Ventilation (P
      < 0.001), number of vent rows (P = 0.009), per-cigarette weight (P < 0.001), and
      filter diameter (P = 0.004) predicted tar yields in high-income countries. Health
      officials must be cognizant of cigarette design issues to provide effective
      regulation of tobacco products.

PMID- 22645623
TI  - Autoimmunity and extrahepatic manifestations in treatment-naive children with
      chronic hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection has been associated with autoimmunity and
      extrahepatic manifestations in adults. Few data are available on these topics in
      children. Nonorgan specific auto-antibodies development is part of the natural
      course of chronic hepatitis C in children. Smooth muscle autoantibody is the most
      common autoantibody found, while liver-kidney microsomal type-1 antibody
      positivity is the most peculiar autoimmune feature of children with HCV
      infection. The clinical significance of non-organ specific autoantibodies in the
      course of paediatric chronic hepatitis C is still debated. Autoantibody
      positivity can be considered neutral for most patients, while it can be
      associated with negative connotations for others, especially those positive for
      liver-kidney microsomal type-1 autoantibody. Subclinical hypothyroidism but not
      autoimmune thyroiditis has been demonstrated in HCV infection in children, while
      only few cases of HCV-associated membranoproliferative glomerulonephritis have
      been described. Single reports are available in the literature reporting the
      anecdotal association between chronic hepatitis C and other extrahepatic
      manifestations such as myopathy and opsoclonus-myoclonus syndrome. Despite the
      low incidence of extrahepatic manifestations of chronic hepatitis C in children,
      overall, available data suggest a careful monitoring.

PMID- 22645622
TI  - Psoriatic disease and tuberculosis nowadays.
AB  - Psoriasis is a chronic, relapsing and remitting inflammatory skin and joint
      disease that has a prevalence of 2-3% in the world's population, whereas of 1-2%
      in Europe. The traditional concept of psoriasis as the "healthy people's" disease
      has been recently revised because of ever-increasing reports of associations with
      various pathological conditions (hypertension, Crohn's disease, type II diabetes
      mellitus, obesity, dyslipidemia, metabolic syndrome, infectious conditions).
      Particularly, advances in psoriasis therapies have introduced biologic agents.
      All the tumor necrosis factor-alpha inhibitors are associated with an increased
      risk of developing active disease in patients with latent tuberculosis infection,
      because of TNF-alpha key role against Mycobacterium tuberculosis. For this
      reason, exclusion of active tuberculosis and treatment of latent tuberculosis
      infection are clinical imperatives prior to starting this therapy. Moreover
      active surveillance for a history of untreated or partially treated tuberculosis
      or latent form has already been shown to be effective in reducing the number of
      incident tuberculosis cases.

PMID- 22645624
TI  - Abeta damages learning and memory in Alzheimer's disease rats with kidney-yang
      deficiency.
AB  - Previous studies demonstrated that Alzheimer's disease was considered as the
      consequence produced by deficiency of Kidney essence. However, the mechanism
      underlying the symptoms also remains elusive. Here we report that spatial
      learning and memory, escape, and swimming capacities were damaged significantly
      in Kidney-yang deficiency rats. Indeed, both hippocampal Abeta(40) and 42
      increases in Kidney-yang deficiency contribute to the learning and memory
      impairments. Specifically, damage of synaptic plasticity is involved in the
      learning and memory impairment of Kidney-yang deficiency rats. We determined that
      the learning and memory damage in Kidney-yang deficiency due to synaptic
      plasticity impairment and increases of Abeta(40) and 42 was not caused via NMDA
      receptor internalization induced by Abeta increase. beta-Adrenergic receptor
      agonist can rescue the impaired long-term potential (LTP) in Kidney-yang rats.
      Taken together, our results suggest that spatial learning and memory inhibited in
      Kidney-yang deficiency might be induced by Abeta increase and the decrease of
      beta(2) receptor function in glia.

PMID- 22645626
TI  - The Protective Effect of Apamin on LPS/Fat-Induced Atherosclerotic Mice.
AB  - Apamin, a peptide component of bee venom (BV), has anti-inflammatory properties.
      However, the molecular mechanisms by which apamin prevents atherosclerosis are
      not fully understood. We examined the effect of apamin on atherosclerotic mice.
      Atherosclerotic mice received intraperitoneal (ip) injections of
      lipopolysaccharide (LPS, 2 mg/kg) to induce atherosclerotic change and were fed
      an atherogenic diet for 12 weeks. Apamin (0.05 mg/kg) was administered by ip
      injection. LPS-induced THP-1-derived macrophage inflammation treated with apamin
      reduced expression of tumor necrosis factor (TNF)-alpha, vascular cell adhesion
      molecule (VCAM)-1, and intracellular cell adhesion molecule (ICAM)-1, as well as
      the nuclear factor kappa B (NF-kappaB) signaling pathway. Apamin decreased the
      formation of atherosclerotic lesions as assessed by hematoxylin and elastic
      staining. Treatment with apamin reduced lipids, Ca(2+) levels, and TNF-alpha in
      the serum from atherosclerotic mice. Further, apamin significantly attenuated
      expression of VCAM-1, ICAM-1, TGF-beta1, and fibronectin in the descending aorta
      from atherosclerotic mice. These results indicate that apamin plays an important
      role in monocyte/macrophage inflammatory processing and may be of potential value
      for preventing atherosclerosis.

PMID- 22645625
TI  - Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the
      Pregnane X Receptor Activation.
AB  - Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are
      common causes of adverse drug effects in some drugs with a narrow therapeutic
      index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is
      predominantly regulated by a nuclear receptor, pregnane X receptor (PXR).
      Sesamin, a major lignan constituent in sesame seeds and oil, exhibits a variety
      of biological functions; however, the effect of sesamin on the modulation of
      CYP3A4 is not well understood. In this study, the effects of sesamin on the PXR
      CYP3A4 pathway were characterized, as well as the underlying mechanisms of those
      effects. Sesamin potently attenuated CYP3A4 induction in a dose-dependent manner
      by blocking the activation of PXR. The PXR inducer-mediated inhibition of CYP3A4
      was further evidenced by the ability of sesamin to attenuate the effects of
      several PXR ligands in the CYP3A4 reporter assay. Further mechanistic studies
      showed that sesamin inhibited PXR by interrupting the interacting with
      coregulators. These results may lead to the development of new therapeutic and
      dietary approaches to reduce the frequency of inducer-drug interaction. Sesamin
      was established as a novel inhibitor of PXR and may be useful for modulating DMEs
      expression and drug efficacies. Modification of CYP3A4 expression and activity by
      consumption of sesamin may have important implications for drug safety.

PMID- 22645627
TI  - In Vitro Cytotoxic Potential of Essential Oils of Eucalyptus benthamii and Its
      Related Terpenes on Tumor Cell Lines.
AB  - Eucalyptus L. is traditionally used for many medicinal purposes. In particular,
      some Eucalyptus species have currently shown cytotoxic properties. Local
      Brazilian communities have used leaves of E. benthamii as a herbal remedy for
      various diseases, including cancer. Considering the lack of available data for
      supporting this cytotoxic effect, the goal of this paper was to study the in
      vitro cytotoxic potential of the essential oils from young and adult leaves of E.
      benthamii and some related terpenes (alpha-pinene, terpinen-4-ol, and gamma
      terpinene) on Jurkat, J774A.1 and HeLa cells lines. Regarding the cytotoxic
      activity based on MTT assay, the essential oils showed improved results than
      alpha-pinene and gamma-terpinene, particularly for Jurkat and HeLa cell lines.
      Terpinen-4-ol revealed a cytotoxic effect against Jurkat cells similar to that
      observed for volatile oils. The results of LDH activity indicated that cytotoxic
      activity of samples against Jurkat cells probably involved cell death by
      apoptosis. The decrease of cell DNA content was demonstrated due to inhibition of
      Jurkat cells proliferation by samples as a result of cytotoxicity. In general,
      the essential oils from young and adult leaves of E. benthamii presented
      cytotoxicity against the investigated tumor cell lines which confirms their
      antitumor potential.

PMID- 22645628
TI  - Ecklonia cava Inhibits Glucose Absorption and Stimulates Insulin Secretion in
      Streptozotocin-Induced Diabetic Mice.
AB  - Aims of study. Present study investigated the effect of Ecklonia cava (EC) on
      intestinal glucose uptake and insulin secretion. Materials and methods.
      Intestinal Na(+)-dependent glucose uptake (SGU) and Na(+)-dependent glucose
      transporter 1 (SGLT1) protein expression was determined using brush border
      membrane vesicles (BBMVs). Glucose-induced insulin secretion was examined in
      pancreatic beta-islet cells. The antihyperglycemic effects of EC, SGU, and SGLT1
      expression were determined in streptozotocin (STZ)-induced diabetic mice.
      Results. Methanol extract of EC markedly inhibited intestinal SGU of BBMV with
      the IC(50) value of 345 MUg/mL. SGLT1 protein expression was dose dependently
      down regulated with EC treatment. Furthermore, insulinotrophic effect of EC
      extract was observed at high glucose media in isolated pancreatic beta-islet
      cells in vitro. We next conducted the antihyperglycemic effect of EC in STZ
      diabetic mice. EC supplementation markedly suppressed SGU and SGLT1 abundance in
      BBMV from STZ mice. Furthermore, plasma insulin level was increased by EC
      treatment in diabetic mice. As a result, EC supplementation improved postprandial
      glucose regulation, assessed by oral glucose tolerance test, in diabetic mice.
      Conclusion. These results suggest that EC play a role in controlling dietary
      glucose absorption at the intestine and insulinotrophic action at the pancreas
      contributing blood glucose homeostasis in diabetic condition.

PMID- 22645629
TI  - Ethanol Extract of Dianthus chinensis L. Induces Apoptosis in Human
      Hepatocellular Carcinoma HepG2 Cells In Vitro.
AB  - Dianthus chinensis L. is used to treat various diseases including cancer;
      however, the molecular mechanism by which the ethanol extract of Dianthus
      chinensis L. (EDCL) induces apoptosis is unknown. In this study, the apoptotic
      effects of EDCL were investigated in human HepG2 hepatocellular carcinoma cells.
      Treatment with EDCL significantly inhibited cell growth in a concentration- and
      time-dependent manner by inducing apoptosis. This induction was associated with
      chromatin condensation, activation of caspases, and cleavage of poly (ADP-ribose)
      polymerase protein. However, apoptosis induced by EDCL was attenuated by caspase
      inhibitor, indicating an important role for caspases in EDCL responses.
      Furthermore, EDCL did not alter the expression of bax in HepG2 cells but did
      selectively downregulate the expression of bcl-2 and bcl-xl, resulting in an
      increase in the ratio of bax:bcl-2 and bax:bcl-xl. These results support a
      mechanism whereby EDCL induces apoptosis through the mitochondrial pathway and
      caspase activation in HepG2 cells.

PMID- 22645630
TI  - Korean red ginseng improves blood pressure stability in patients with
      intradialytic hypotension.
AB  - Introduction. Intradialytic hypotension (IDH) is a common complication during
      hemodialysis which may increase mortality risks. Low dose of Korean red ginseng
      (KRG) has been reported to increase blood pressure. Whether KRG can improve
      hemodynamic stability during hemodialysis has not been examined. Methods. The 8
      week study consisted of two phases: observation phase and active treatment phase.
      According to prehemodialysis blood pressure (BP), 38 patients with IDH were
      divided into group A (BP >= 140/90 mmHg, n = 18) and group B (BP < 140/90 mmHg, n
      = 20). Patients were instructed to chew 3.5 gm KRG slices at each hemodialysis
      session during the 4-week treatment phase. Blood pressure changes, number of
      sessions disturbed by symptomatic IDH, plasma levels of vasoconstrictors, blood
      biochemistry, and adverse effects were recorded. Results. KRG significantly
      reduced the degree of blood pressure drop during hemodialysis (P < 0.05) and the
      frequency of symptomatic IDH (P < 0.05). More activation of vasoconstrictors
      (endothelin-1 and angiotensin II) during hemodialysis was found. The postdialytic
      levels of endothelin-1 and angiotensin II increased significantly (P < 0.01).
      Conclusion. Chewing KRG renders IDH patients better resistance to acute BP
      reduction during hemodialysis via activation of vasoconstrictors. Our results
      suggest that KRG could be an adjuvant treatment for IDH.

PMID- 22645631
TI  - Dexmedetomidine protects against lipid peroxidation and erythrocyte deformability
      alterations in experimental hepatic ischemia reperfusion injury.
AB  - BACKGROUND: Hepatic ischemia-reperfusion injury is a common clinical problem in
      hepatic surgery and transplantation. Several cellular and tissue structural and
      functional alterations are observed in such injury. The aim of this study was to
      evaluate the effect of dexmedetomidine on lipid peroxidation and erythrocyte
      deformability during ischemia-reperfusion injury in rats. METHODS: Twenty-four
      Wistar Albino rats were randomly separated into three groups as control (C),
      ischemia-reperfusion injury (I/R) and dexmedetomidine group (I/R-D). Ischemia was
      induced with portal clampage for 45 min and reperfusion period was 45 min after
      declampage. Group I/R-D received dexmedetomidine 100 ug/kg i.p. 30 min before
      portal clampage. Serum malondialdehyde and superoxide dismutase activities to
      document lipid peroxidation and erythrocyte deformability index were
      investigated. RESULTS: Serum superoxide dismutase and malondialdehyde activity
      levels were significantly higher and erythrocyte deformability index was
      decreased in hepatic ischemia-reperfusion group. However, these changes were
      observed to be prevented with dexmedetomidine treatment when given before portal
      clampage. CONCLUSION: These findings clearly indicate that erythrocyte
      deformability index is decreased in hepatic ischemia reperfusion injury and has a
      potential role to prevent these alterations. The protective effect of
      dexmedetomidine on hepatic I/R injury is also decreased lipid peroxidation.
      Further experimental and clinical investigations may clarify the molecular
      mechanisms and clinical significance of these findings.

PMID- 22645632
TI  - Multiple cells of origin in cholangiocarcinoma underlie biological,
      epidemiological and clinical heterogeneity.
AB  - Recent histological and molecular characterization of cholangiocarcinoma (CCA)
      highlights the heterogeneity of this cancer that may emerge at different sites of
      the biliary tree and with different macroscopic or morphological features.
      Furthermore, different stem cell niches have been recently described in the liver
      and biliary tree, suggesting this as the basis of the heterogeneity of
      intrahepatic (IH)- and extrahepatic (EH)-CCAs, which are two largely different
      tumors from both biological and epidemiological points of view. The complexity of
      the organization of the liver stem cell compartments could underlie the CCA
      clinical-pathological heterogeneity and the criticisms in classifying primitive
      liver tumors. These recent advances highlight a possible new classification of
      CCAs based on cells of origin and this responds to the need of generating
      homogenous diagnostic, prognostic and, hopefully, therapeutic categories of IH-
      and EH-CCAs.

PMID- 22645633
TI  - Relationship between HER-2 overexpression and brain metastasis in esophageal
      cancer patients.
AB  - AIM: To study if HER-2 overexpression by locally advanced esophageal cancers
      increase the chance of brain metastasis following esophagectomy. METHODS: We
      retrospectively reviewed the medical records of esophageal cancer patients who
      underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000
      and 2010. Data analyzed consisted of demographic and clinical variables. The
      brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA
      approved DAKO Hercept Test((r)). RESULTS: One hundred and forty two patients were
      reviewed. Median age was 64 years (36-86 years). Eighty eight patients (62%)
      received neoadjuvant chemoradiotherapy. Pathological complete and partial
      responses were achieved in 17 (19%) and 71 (81%) patients. Cancer relapsed in
      43/142 (30%) patients. The brain was the first site of relapse in 9/43 patients
      (21%, 95% CI: 10%-36%). HER-2 immunohistochemistry testing of the brain
      metastasis tissue showed that 5/9 (56%) cases overexpressed HER-2 (3+ staining).
      CONCLUSION: HER-2 overexpression might be associated with increased risk of brain
      metastasis in esophageal cancer patients following esophagectomy. Further studies
      will be required to validate this observation.

PMID- 22645634
TI  - Analysis of liver metastasis after resection for pancreatic ductal
      adenocarcinoma.
AB  - AIM: To investigate the risk factors affecting the liver metastasis (LM) of
      pancreatic ductal adenocarcinoma (PDAC) after resection. METHODS: We
      retrospectively analyzed 101 PDAC patients who underwent surgical resection at
      the Samsung Medical Center between January 2000 and December 2004. Forty one
      patients with LM were analyzed for the time of metastasis, prognostic factors
      affecting LM, and survival. RESULTS: LM was found in 40.6%. The median time of
      the LM (n = 41) was 6.0 +/- 4.6 mo and most LM occurred within 1 year. In
      univariate analysis, tumor size, preoperative carbohydrate antigen 19-9, and
      perineural invasion were factors affecting LM after resection. In multivariate
      analysis, tumor size was the most important factor for LM. In univariate
      analysis, tumor cell differentiation was significant to LM in low-risk groups.
      CONCLUSION: LM after resection of PDAC occurs early and shows poor survival.
      Tumor size is the key indicator for LM after resection.

PMID- 22645635
TI  - A case of severe acalculous cholecystitis associated with sorafenib treatment for
      advanced hepatocellular carcinoma.
AB  - Sorafenib, a multikinase inhibitor, is the first and only drug, which improves
      significantly the overall survival in patients with advanced hepatocellular
      carcinoma (HCC). However, many patients experience diverse side effects, some of
      them severe and unexpected. To date, acute acalculous cholecystitis has not been
      documented in association with a HCC patient treated with sorafenib. Here, we
      report the case of a 43-year-old woman with hepatitis C virus-related advanced
      HCC. She received sorafenib, and later complained of a sudden onset of severe
      right hypocondrial pain with rebound tenderness and muscle defense. Laboratory
      examination showed mild elevation of transaminases, biliary enzymes, bilirubin,
      inflammation markers, and a marked peripheral eosinophilia. Abdominal computed
      tomography (CT) revealed a swollen gallbladder with exudate associated with
      severe inflammation without stones or debris. Consequently, sorafenib treatment
      was stopped immediately, and steroid-pulse therapy was performed. Steroid therapy
      drastically improved all clinical manifestations along with normalization of CT
      findings, eosinophilia, and liver functions. In summary, we herein report a rare
      case of acute severe acalculous cholecystitis associated with sorafenib in the
      patient with advanced HCC.

PMID- 22645636
TI  - Greater omentum gastrointestinal stromal tumor with PDGFRA-mutation and
      hemoperitoneum.
AB  - Although gastrointestinal stromal tumor (GIST) occurs generally in the digestive
      tract, omental GIST is very rare. We report the first case of an adult greater
      omental GIST with a new platelet-derived growth factor receptor alpha gene
      (PDGFRA)-mutation with hemoperitoneum. A 43-year-old man was admitted to our
      hospital complaining of acute abdominal pain. Abdominal contrast-enhanced
      computed tomography revealed a huge mass in the right abdominal cavity, and a
      large accumulation of fluid in the pelvic cavity, suggesting hemoperitoneum. We
      diagnosed the rupture as an intra-abdominal tumor, and an emergency tumorectomy
      was performed with resection of the greater omentum. This tumor was located in
      the distal right side of the greater omentum, and showed no continuity with the
      gastric wall. The tumor occurred primarily in the greater omentum. The resected
      tumor was about 19 cm * 12 cm * 14 cm in diameter, and weighed 1529 g.
      Histologically, the tumor was composed of epithelioid-shaped cells with high
      cellularity, and was positive for CD117 and CD34, and negative for S-100, alpha
      smooth muscle actin. The mitosis was 6/50 under high power field. This case
      showed exon 18 mutation of PDGFRA with 846 (Asp to Glu) substitution, 848 (Asn to
      Lys) substitution. This is the first report of this PDGFRA mutation in omental
      GIST, and this might play an important role in the tumorigenesis of this case.
      Based on these findings, the tumor was diagnosed as high risk GIST primarily
      occurring in the greater omentum. The patient was treated with imatinib at a dose
      of 400 mg/d as adjuvant chemotherapy, and has been followed up for 24 mo with no
      evidence of recurrence.

PMID- 22645638
TI  - Curcumin attenuates Nrf2 signaling defect, oxidative stress in muscle and glucose
      intolerance in high fat diet-fed mice.
AB  - AIM: To investigate the signaling mechanism of anti-oxidative action by curcumin
      and its impact on glucose disposal. METHODS: Male C57BL/6J mice were fed with
      either a normal diet (n = 10) or a high fat diet (HFD) (n = 20) to induce obesity
      and insulin resistance. After 16 wk, 10 HFD-fed mice were further treated with
      daily curcumin oral gavage at the dose of 50 mg/kg body weight (BW) (HFD +
      curcumin group). After 15 d of the curcumin supplementation, an intraperitoneal
      glucose tolerance test was performed. Fasting blood samples were also collected
      for insulin and glucose measurements. Insulin-sensitive tissues, including
      muscle, adipose tissue and the liver, were isolated for the assessments of
      malondialdehyde (MDA), reactive oxygen species (ROS) and nuclear factor erythroid
      2-related factor-2 (Nrf2) signaling. RESULTS: We show here that in a HFD mouse
      model, short-term curcumin gavage attenuated glucose intolerance without
      affecting HFD-induced BW gain. Curcumin also attenuated HFD-induced elevations of
      MDA and ROS in the skeletal muscle, particularly in its mitochondrial fraction,
      but it had no such an effect in either adipose tissue or the liver of HFD-fed
      mice. Correspondingly, in skeletal muscle, the levels of total or nuclear content
      of Nrf2, as well as its downstream target, heme oxygenase-1, were reduced by HFD
      feeding. Curcumin intervention dramatically reversed these defects in Nrf2
      signaling. Further analysis of the relationship of oxidative stress with glucose
      level by a regression analysis showed a positive and significant correlation
      between the area under the curve of a glucose tolerance test with MDA levels
      either in muscle or muscular mitochondria. CONCLUSION: These findings suggest
      that the short-term treatment of curcumin in HFD-fed mice effectively ameliorates
      muscular oxidative stress by activating Nrf2 function that is a novel mechanism
      for its effect in improving glucose intolerance.

PMID- 22645639
TI  - Lipoprotein(a) in type 2 diabetic subjects and its relationship to diabetic
      microvascular complications.
AB  - AIM: To estimate the level of serum lipoprotein (a) [Lp (a)] in type 2 diabetes
      mellitus patients and to determine the relationship between Lp(a) in type 2
      diabetes mellitus patients and micro-vascular complications. METHODS: A cross
      sectional study was performed that enrolled 144 subjects with type 2 diabetes
      mellitus above the age of 25 years attending outpatient clinic of Government
      Medical College, Kozhikode. Lp(a) levels were measured quantitatively in venous
      samples using Turbidimetric Immunoassay in all subjects. Each patient was
      evaluated for micro vascular complications, namely diabetic retinopathy,
      nephropathy and neuropathy. The relationship between Lp(a) levels and the micro
      vascular complications was assessed by univariate analysis. RESULTS: Mean age of
      cases was 53.93 +/- 10.74 years with a male to female ratio of 1.3:1. Mean
      duration of diabetes was 9.53 +/- 7.3 years. Abnormal Lp(a) levels (>= 30 mg/dL)
      were observed in 38 (26.4%) diabetic subjects. Seventy-eight (54.16%) cases had
      diabetic nephropathy and significantly higher Lp(a) levels were found among these
      cases [Median 28.2 mg/dL (Interquartile range; IQR 24.4-33.5) vs 19.3 mg/dL (IQR
      14.7-23.5); P < 0.05]. Retinopathy was present among 66 (45.13%) cases and
      peripheral neuropathy was detected among 54 (37.5%) cases. However, Lp(a) levels
      were not significantly different among those with or without retinopathy and
      neuropathy. Positive correlation was found between higher Lp(a) levels and
      duration of diabetes (r = 0.165, P < 0.05) but not with HbA1c values (r = -
      0.083). CONCLUSION: Abnormal Lp(a) levels were found among 26.4% of diabetic
      subjects. Patients with diabetic nephropathy had higher Lp(a) levels. No
      association was found between Lp(a) levels and diabetic retinopathy or
      neuropathy. Longer duration of diabetes correlated with higher Lp(a) levels.

PMID- 22645637
TI  - Diabetes-related alterations in the enteric nervous system and its
      microenvironment.
AB  - Gastric intestinal symptoms common among diabetic patients are often caused by
      intestinal motility abnormalities related to enteric neuropathy. It has recently
      been demonstrated that the nitrergic subpopulation of myenteric neurons are
      especially susceptible to the development of diabetic neuropathy. Additionally,
      different susceptibility of nitrergic neurons located in different intestinal
      segments to diabetic damage and their different levels of responsiveness to
      insulin treatment have been revealed. These findings indicate the importance of
      the neuronal microenvironment in the pathogenesis of diabetic nitrergic
      neuropathy. The main focus of this review therefore was to summarize recent
      advances related to the diabetes-related selective nitrergic neuropathy and
      associated motility disturbances. Special attention was given to the findings on
      capillary endothelium and enteric glial cells. Growing evidence indicates that
      capillary endothelium adjacent to the myenteric ganglia and enteric glial cells
      surrounding them are determinative in establishing the ganglionic
      microenvironment. Additionally, recent advances in the development of new
      strategies to improve glycemic control in type 1 and type 2 diabetes mellitus are
      also considered in this review. Finally, looking to the future, the recent and
      promising results of metagenomics for the characterization of the gut microbiome
      in health and disease such as diabetes are highlighted.

PMID- 22645640
TI  - Hair organ regeneration via the bioengineered hair follicular unit
      transplantation.
AB  - Organ regenerative therapy aims to reproduce fully functional organs to replace
      organs that have been lost or damaged as a result of disease, injury, or aging.
      For the fully functional regeneration of ectodermal organs, a concept has been
      proposed in which a bioengineered organ is developed by reproducing the embryonic
      processes of organogenesis. Here, we show that a bioengineered hair follicle
      germ, which was reconstituted with embryonic skin-derived epithelial and
      mesenchymal cells and ectopically transplanted, was able to develop
      histologically correct hair follicles. The bioengineered hair follicles properly
      connected to the host skin epithelium by intracutaneous transplantation and
      reproduced the stem cell niche and hair cycles. The bioengineered hair follicles
      also autonomously connected with nerves and the arrector pili muscle at the
      permanent region and exhibited piloerection ability. Our findings indicate that
      the bioengineered hair follicles could restore physiological hair functions and
      could be applicable to surgical treatments for alopecia.

PMID- 22645641
TI  - Muscle or liver-specific Sirt3 deficiency induces hyperacetylation of
      mitochondrial proteins without affecting global metabolic homeostasis.
AB  - Sirt3 is a mitochondrial sirtuin, predominantly expressed in highly metabolic
      tissues. Germline ablation of Sirt3 has major metabolic consequences, including
      increased susceptibility to metabolic damage and oxidative stress after high fat
      feeding. In order to determine the contribution of liver and skeletal muscle to
      these phenotypes, we generated muscle-specific Sirt3 (Sirt3(skm-/-)) and liver
      specific Sirt3 (Sirt3(hep-/-)) knock-out mice. Despite a marked global
      hyperacetylation of mitochondrial proteins, Sirt3(skm-/-) and Sirt3(hep-/-) mice
      did not manifest any overt metabolic phenotype under either chow or high fat diet
      conditions. Similarly, there was no evidence for increased oxidative stress in
      muscle or liver when Sirt3 was ablated in a tissue-specific manner. These
      observations suggest that the mitochondrial hyperacetylation induced by Sirt3
      deletion in a tissue specific manner is not necessarily linked to mitochondrial
      dysfunction and does not recapitulate the metabolic abnormalities observed in the
      germline Sirt3 knock-out mice.

PMID- 22645642
TI  - Observation of superconductivity at 30~46 K in A(x)Fe2Se2(A = Li, Na, Ba, Sr, Ca,
      Yb, and Eu).
AB  - New iron selenide superconductors by intercalating smaller-sized alkali metals
      (Li, Na) and alkaline earths using high-temperature routes have been pursued ever
      since the discovery of superconductivity at about 30 K in KFe2Se2, but all have
      failed so far. Here we demonstrate that a series of superconductors with enhanced
      T(c) = 30~46 K can be obtained by intercalating metals, Li, Na, Ba, Sr, Ca, Yb,
      and Eu in between FeSe layers by the ammonothermal method at room temperature.
      Analysis on their powder X-ray diffraction patterns reveals that all the main
      phases can be indexed based on body-centered tetragonal lattices with a~3.755
      3.831 A while c~15.99-20.54 A. Resistivities show the corresponding sharp
      transitions at 45 K and 39 K for NaFe2Se2 and Ba0.8Fe2Se2, respectively,
      confirming their bulk superconductivity. These findings provide a new starting
      point for studying the properties of these superconductors and an effective
      synthetic route for the exploration of new superconductors as well.

PMID- 22645643
TI  - Porous iron oxide ribbons grown on graphene for high-performance lithium storage.
AB  - A well-designed nanostructure of transition metal oxides has been regarded as a
      key to solve their problems of large volume changes during lithium insertion
      desertion processes which are associated with pulverization of the electrodes and
      rapid capacity decay. Here we report an effective approach for the fabrication of
      porous iron oxide ribbons by controlling the nucleation and growth of iron
      precursor onto the graphene surface and followed by an annealing treatment. The
      resultant iron oxide ribbons possess large aspect ratio, porous structure, thin
      feature and enhanced open-edges. These characteristics are favorable for the fast
      diffusion of lithium ions and electrons, and meanwhile can effectively
      accommodate the volume change of iron oxides during the cycling processes. As a
      consequence, the graphene-induced porous iron oxide ribbons exhibit a high
      reversible capacity and excellent cycle stability for lithium storage.

PMID- 22645644
TI  - siRNA off-target effects in genome-wide screens identify signaling pathway
      members.
AB  - We introduce a method for analyzing small interfering RNA (siRNA) genetic screens
      based entirely on off-target effects. Using a screen for members of the Wnt
      pathway, we demonstrate that this method identifies known pathway components,
      some of which are not present in the screening library. This technique can be
      applied to siRNA screen results retroactively to confirm positives and identify
      genes missed using conventional methods for on-target gene selection.

PMID- 22645645
TI  - Computer-assisted and fractal-based morphometric assessment of microvascularity
      in histological specimens of gliomas.
AB  - Fractal analysis is widely applied to investigate the vascular system in
      physiological as well as pathological states. We propose and examine a computer
      aided and fractal-based image analysis technique to quantify the microvascularity
      in histological specimens of WHO grade II and III gliomas. A computer-aided and
      fractal-based analysis was used to describe the microvessels and to quantify
      their geometrical complexity in histological specimens collected from 17
      patients. The statistical analysis showed that the fractal-based indexes are the
      most discriminant parameters to describe the microvessels. The computer-aided
      quantitative analysis also showed that grade III gliomas are generally more
      vascularized than grade II gliomas. The fractal parameters are reliable
      quantitative indicators of the neoplastic microvasculature, making them potential
      surrogate biomarkers. The qualitative evaluation currently performed by the
      neuropathologist can be combined with the computer-assisted quantitative analysis
      of the microvascularity to improve the diagnosis and optimize the treatment of
      patients with brain cancer.

PMID- 22645647
TI  - Combined high-resolution genotyping and geospatial analysis reveals modes of
      endemic urban typhoid fever transmission.
AB  - Typhoid is a systemic infection caused by Salmonella Typhi and Salmonella
      Paratyphi A, human-restricted bacteria that are transmitted faeco-orally.
      Salmonella Typhi and S. Paratyphi A are clonal, and their limited genetic
      diversity has precluded the identification of long-term transmission networks in
      areas with a high disease burden. To improve our understanding of typhoid
      transmission we have taken a novel approach, performing a longitudinal spatial
      case-control study for typhoid in Nepal, combining single-nucleotide polymorphism
      genotyping and case localization via global positioning. We show extensive
      clustering of typhoid occurring independent of population size and density. For
      the first time, we demonstrate an extensive range of genotypes existing within
      typhoid clusters, and even within individual households, including some resulting
      from clonal expansion. Furthermore, although the data provide evidence for direct
      human-to-human transmission, we demonstrate an overwhelming contribution of
      indirect transmission, potentially via contaminated water. Consistent with this,
      we detected S. Typhi and S. Paratyphi A in water supplies and found that typhoid
      was spatially associated with public water sources and low elevation. These
      findings have implications for typhoid-control strategies, and our innovative
      approach may be applied to other diseases caused by other monophyletic or
      emerging pathogens.

PMID- 22645649
TI  - Cell cycle commitment in budding yeast emerges from the cooperation of multiple
      bistable switches.
AB  - The start-transition (START) in the G1 phase marks the point in the cell cycle at
      which a yeast cell initiates a new round of cell division. Once made, this
      decision is irreversible and the cell is committed to progressing through the
      entire cell cycle, irrespective of arrest signals such as pheromone. How
      commitment emerges from the underlying molecular interaction network is poorly
      understood. Here, we perform a dynamical systems analysis of an established cell
      cycle model, which has never been analysed from a commitment perspective. We show
      that the irreversibility of the START transition and subsequent commitment can be
      consistently explained in terms of the interplay of multiple bistable molecular
      switches. By applying an existing mathematical model to a novel problem and by
      expanding the model in a self-consistent manner, we achieve several goals: we
      bring together a large number of experimental findings into a coherent
      theoretical framework; we increase the scope and the applicability of the
      original model; we give a systems level explanation of how the START transition
      and the cell cycle commitment arise from the dynamical features of the underlying
      molecular interaction network; and we make clear, experimentally testable
      predictions.

PMID- 22645648
TI  - The reverse, but coordinated, roles of Tor2 (TORC1) and Tor1 (TORC2) kinases for
      growth, cell cycle and separase-mediated mitosis in Schizosaccharomyces pombe.
AB  - Target of rapamycin complexes (TORCs), which are vital for nutrient utilization,
      contain a catalytic subunit with the phosphatidyl inositol kinase-related kinase
      (PIKK) motif. TORC1 is required for cell growth, while the functions of TORC2 are
      less well understood. We show here that the fission yeast Schizosaccharomyces
      pombe TORC2 has a cell cycle role through determining the proper timing of Cdc2
      Tyr15 dephosphorylation and the cell size under limited glucose, whereas TORC1
      restrains mitosis and opposes securin-separase, which are essential for
      chromosome segregation. These results were obtained using the previously isolated
      TORC1 mutant tor2-L2048S in the phosphatidyl inositol kinase (PIK) domain and a
      new TORC2 mutant tor1-L2045D, which harbours a mutation in the same site. While
      mutated TORC1 and TORC2 displayed diminished kinase activity and FKBP12/Fkh1
      dependent rapamycin sensitivity, their phenotypes were nearly opposite in
      mitosis. Premature mitosis and the G2-M delay occurred in TORC1 and TORC2
      mutants, respectively. Surprisingly, separase/cut1-securin/cut2 mutants were
      rescued by TORC1/tor2-L2048S mutation or rapamycin addition or even Fkh1
      deletion, whereas these mutants showed synthetic defect with TORC2/tor1-L2045D.
      TORC1 and TORC2 coordinate growth, mitosis and cell size control, such as Wee1
      and Cdc25 do for the entry into mitosis.

PMID- 22645650
TI  - Labile disulfide bonds are common at the leucocyte cell surface.
AB  - Redox conditions change in events such as immune and platelet activation, and
      during viral infection, but the biochemical consequences are not well
      characterized. There is evidence that some disulfide bonds in membrane proteins
      are labile while others that are probably structurally important are not exposed
      at the protein surface. We have developed a proteomic/mass spectrometry method to
      screen for and identify non-structural, redox-labile disulfide bonds in leucocyte
      cell-surface proteins. These labile disulfide bonds are common, with several
      classes of proteins being identified and around 30 membrane proteins regularly
      identified under different reducing conditions including using enzymes such as
      thioredoxin. The proteins identified include integrins, receptors, transporters
      and cell-cell recognition proteins. In many cases, at least one cysteine residue
      was identified by mass spectrometry as being modified by the reduction process.
      In some cases, functional changes are predicted (e.g. in integrins and cytokine
      receptors) but the scale of molecular changes in membrane proteins observed
      suggests that widespread effects are likely on many different types of proteins
      including enzymes, adhesion proteins and transporters. The results imply that
      membrane protein activity is being modulated by a 'redox regulator' mechanism.

PMID- 22645651
TI  - Discovery of catalytically active orthologues of the Parkinson's disease kinase
      PINK1: analysis of substrate specificity and impact of mutations.
AB  - Missense mutations of the phosphatase and tensin homolog (PTEN)-induced kinase 1
      (PINK1) gene cause autosomal-recessive Parkinson's disease. To date, little is
      known about the intrinsic catalytic properties of PINK1 since the human enzyme
      displays such low kinase activity in vitro. We have discovered that, in contrast
      to mammalian PINK1, insect orthologues of PINK1 we have investigated-namely
      Drosophila melanogaster (dPINK1), Tribolium castaneum (TcPINK1) and Pediculus
      humanus corporis (PhcPINK1)-are active as judged by their ability to
      phosphorylate the generic substrate myelin basic protein. We have exploited the
      most active orthologue, TcPINK1, to assess its substrate specificity and
      elaborated a peptide substrate (PINKtide, KKWIpYRRSPRRR) that can be employed to
      quantify PINK1 kinase activity. Analysis of PINKtide variants reveal that PINK1
      phosphorylates serine or threonine, but not tyrosine, and we show that PINK1
      exhibits a preference for a proline at the +1 position relative to the
      phosphorylation site. We have also, for the first time, been able to investigate
      the effect of Parkinson's disease-associated PINK1 missense mutations, and found
      that nearly all those located within the kinase domain, as well as the C-terminal
      non-catalytic region, markedly suppress kinase activity. This emphasizes the
      crucial importance of PINK1 kinase activity in preventing the development of
      Parkinson's disease. Our findings will aid future studies aimed at understanding
      how the activity of PINK1 is regulated and the identification of physiological
      substrates.

PMID- 22645652
TI  - The Adenomatous polyposis coli tumour suppressor is essential for Axin complex
      assembly and function and opposes Axin's interaction with Dishevelled.
AB  - Most cases of colorectal cancer are linked to mutational inactivation of the
      Adenomatous polyposis coli (APC) tumour suppressor. APC downregulates Wnt
      signalling by enabling Axin to promote the degradation of the Wnt signalling
      effector beta-catenin (Armadillo in flies). This depends on Axin's DIX domain
      whose polymerization allows it to form dynamic protein assemblies
      ('degradasomes'). Axin is inactivated upon Wnt signalling, by
      heteropolymerization with the DIX domain of Dishevelled, which recruits it into
      membrane-associated 'signalosomes'. How APC promotes Axin's function is unclear,
      especially as it has been reported that APC's function can be bypassed by
      overexpression of Axin. Examining apc null mutant Drosophila tissues, we
      discovered that APC is required for Axin degradasome assembly, itself essential
      for Armadillo downregulation. Degradasome assembly is also attenuated in APC
      mutant cancer cells. Notably, Axin becomes prone to Dishevelled-dependent plasma
      membrane recruitment in the absence of APC, indicating a crucial role of APC in
      opposing the interaction of Axin with Dishevelled. Indeed, co-expression
      experiments reveal that APC displaces Dishevelled from Axin assemblies, promoting
      degradasome over signalosome formation in the absence of Wnts. APC thus empowers
      Axin to function in two ways-by enabling its DIX-dependent self-assembly, and by
      opposing its DIX-dependent copolymerization with Dishevelled and consequent
      inactivation.

PMID- 22645653
TI  - Chronic pulmonary cavitary tuberculosis in rabbits: a failed host immune
      response.
AB  - The molecular determinants of the immune response to Mycobacterium tuberculosis
      HN878 infection in a rabbit model of pulmonary cavitary tuberculosis were
      studied. Aerosol infection of rabbits resulted in a highly differentially
      expressed global transcriptome in the lungs at 2 weeks, which dropped at 4 weeks
      and then gradually increased. While IFNgamma was progressively upregulated
      throughout the infection, several other genes in the IFNgamma network were not. T
      cell activation network genes were gradually upregulated and maximally induced at
      12 weeks. Similarly, the IL4 and B-cell activation networks were progressively
      upregulated, many reaching high levels between 12 and 16 weeks. Delayed peak
      expression of genes associated with macrophage activation and Th1 type immunity
      was noted. Although spleen CD4(+) and CD8(+) T cells showed maximal tuberculosis
      antigen-specific activation by 8 weeks, macrophage activation in lungs, lymph
      nodes and spleen did not peak until 12 weeks. In the lungs, infecting bacilli
      grew exponentially up to 4 weeks, followed by a steady-state high bacillary load
      to 12 weeks that moderately increased during cavitation at 16 weeks. Thus, the
      outcome of HN878 infection of rabbits was determined early during infection by a
      suboptimal activation of innate immunity and delayed T-cell activation.

PMID- 22645654
TI  - Opposing role of condensin hinge against replication protein A in mitosis and
      interphase through promoting DNA annealing.
AB  - Condensin is required for chromosome dynamics and diverse DNA metabolism. How
      condensin works, however, is not well understood. Condensin contains two
      structural maintenance of chromosomes (SMC) subunits with the terminal globular
      domains connected to coiled-coil that is interrupted by the central hinge.
      Heterotrimeric non-SMC subunits regulate SMC. We identified a novel fission yeast
      SMC hinge mutant, cut14-Y1, which displayed defects in DNA damage repair and
      chromosome segregation. It contains an amino acid substitution at a conserved
      hinge residue of Cut14/SMC2, resulting in diminished DNA binding and annealing. A
      replication protein A mutant, ssb1-418, greatly alleviated the repair and mitotic
      defects of cut14-Y1. Ssb1 protein formed nucleolar foci in cut14-Y1 cells, but
      the number of foci was diminished in cut14-Y1 ssb1-418 double mutants. Consistent
      with the above results, Ssb1 protein bound to single-strand DNA was removed by
      condensin or the SMC dimer through DNA reannealing in vitro. Similarly, RNA
      hybridized to DNA may be removed by the SMC dimer. Thus, condensin may wind up
      DNA strands to unload chromosomal components after DNA repair and prior to
      mitosis. We show that 16 suppressor mutations of cut14-Y1 were all mapped within
      the hinge domain, which surrounded the original L543 mutation site.

PMID- 22645655
TI  - Structure and function of the transketolase from Mycobacterium tuberculosis and
      comparison with the human enzyme.
AB  - The transketolase (TKT) enzyme in Mycobacterium tuberculosis represents a novel
      drug target for tuberculosis treatment and has low homology with the orthologous
      human enzyme. Here, we report on the structural and kinetic characterization of
      the transketolase from M. tuberculosis (TBTKT), a homodimer whose monomers each
      comprise 700 amino acids. We show that TBTKT catalyses the oxidation of donor
      sugars xylulose-5-phosphate and fructose-6-phosphate as well as the reduction of
      the acceptor sugar ribose-5-phosphate. An invariant residue of the TKT consensus
      sequence required for thiamine cofactor binding is mutated in TBTKT; yet its
      catalytic activities are unaffected, and the 2.5 A resolution structure of full
      length TBTKT provides an explanation for this. Key structural differences between
      the human and mycobacterial TKT enzymes that impact both substrate and cofactor
      recognition and binding were uncovered. These changes explain the kinetic
      differences between TBTKT and its human counterpart, and their differential
      inhibition by small molecules. The availability of a detailed structural model of
      TBTKT will enable differences between human and M. tuberculosis TKT structures to
      be exploited to design selective inhibitors with potential antitubercular
      activity.

PMID- 22645656
TI  - Drosophila poly suggests a novel role for the Elongator complex in insulin
      receptor-target of rapamycin signalling.
AB  - Multi-cellular organisms need to successfully link cell growth and metabolism to
      environmental cues during development. Insulin receptor-target of rapamycin (InR
      TOR) signalling is a highly conserved pathway that mediates this link. Herein, we
      describe poly, an essential gene in Drosophila that mediates InR-TOR signalling.
      Loss of poly results in lethality at the third instar larval stage, but only
      after a stage of extreme larval longevity. Analysis in Drosophila demonstrates
      that Poly and InR interact and that poly mutants show an overall decrease in InR
      TOR signalling, as evidenced by decreased phosphorylation of Akt, S6K and 4E-BP.
      Metabolism is altered in poly mutants, as revealed by microarray expression
      analysis and a decreased triglyceride : protein ratio in mutant animals.
      Intriguingly, the cellular distribution of Poly is dependent on insulin
      stimulation in both Drosophila and human cells, moving to the nucleus with
      insulin treatment, consistent with a role in InR-TOR signalling. Together, these
      data reveal that Poly is a novel, conserved (from flies to humans) mediator of
      InR signalling that promotes an increase in cell growth and metabolism.
      Furthermore, homology to small subunits of Elongator demonstrates a novel,
      unexpected role for this complex in insulin signalling.

PMID- 22645657
TI  - Interleukin-2 signalling is modulated by a labile disulfide bond in the CD132
      chain of its receptor.
AB  - Certain disulfide bonds present in leucocyte membrane proteins are labile and can
      be reduced in inflammation. This can cause structural changes that result in
      downstream functional effects, for example, in integrin activation. Recent
      studies have shown that a wide range of membrane proteins have labile disulfide
      bonds including CD132, the common gamma chain of the receptors for several
      cytokines including interleukin-2 and interleukin-4 (IL-2 and IL-4). The Cys(183)
      Cys(232) disulfide bond in mouse CD132 is susceptible to reduction by enzymes
      such as thioredoxin (TRX), gamma interferon-inducible lysosomal thiolreductase
      and protein disulfide isomerase, which are commonly secreted during immune
      activation. The Cys(183)-Cys(232) disulfide bond is also reduced in an in vivo
      lipopolysaccharide (LPS)-induced acute model of inflammation. Conditions that
      lead to the reduction of the Cys(183)-Cys(232) disulfide bond in CD132 inhibit
      proliferation of an IL-2-dependent T cell clone and concomitant inhibition of the
      STAT-5 signalling pathway. The same reducing conditions had no effect on the
      proliferation of an IL-2-independent T cell clone, nor did they reduce disulfide
      bonds in IL-2 itself. We postulate that reduction of the Cys(183)-Cys(232)
      disulfide in CD132 inhibits IL-2 binding to the receptor complex. Published data
      show that the Cys(183)-Cys(232) disulfide bond is exposed at the surface of CD132
      and in close contact with IL-2 and IL-4 in their respective receptor complexes.
      In addition, mutants in these Cys residues in human CD132 lead to
      immunodeficiency and loss of IL-2 binding. These results have wider implications
      for the regulation of cytokine receptors in general, as their activity can be
      modulated by a 'redox regulator' mechanism caused by the changes in the redox
      environment that occur during inflammation and activation of the immune system.

PMID- 22645658
TI  - Spatiotemporal dynamics of Spc105 regulates the assembly of the Drosophila
      kinetochore.
AB  - The formation of kinetochores shortly before each cell division is a prerequisite
      for proper chromosome segregation. The synchronous mitoses of Drosophila
      syncytial embryos have provided an ideal in vivo system to follow kinetochore
      assembly kinetics and so address the question of how kinetochore formation is
      regulated. We found that the nuclear exclusion of the Spc105/KNL1 protein during
      interphase prevents precocious assembly of the Mis12 complex. The nuclear import
      of Spc105 in early prophase and its immediate association with the Mis12 complex
      on centromeres are thus the first steps in kinetochore assembly. The cumulative
      kinetochore levels of Spc105 and Mis12 complex then determine the rate of Ndc80
      complex recruitment commencing only after nuclear envelope breakdown. The carboxy
      terminal part of Spc105 directs its nuclear import and is sufficient for the
      assembly of all core kinetochore components and CENP-C, when localized
      ectopically to centrosomes. Super-resolution microscopy shows that carboxy
      terminus of Spc105 lies at the junction of the Mis12 and Ndc80 complexes on
      stretched kinetochores. Our study thus indicates that physical accessibility of
      kinetochore components plays a crucial role in the regulation of Drosophila
      kinetochore assembly and leads us to a model in which Spc105 is a licensing
      factor for its onset.

PMID- 22645659
TI  - A modular and optimized single marker system for generating Trypanosoma brucei
      cell lines expressing T7 RNA polymerase and the tetracycline repressor.
AB  - Here, we present a simple modular extendable vector system for introducing the T7
      RNA polymerase and tetracycline repressor genes into Trypanosoma brucei. This
      novel system exploits developments in our understanding of gene expression and
      genome organization to produce a streamlined plasmid optimized for high levels of
      expression of the introduced transgenes. We demonstrate the utility of this novel
      system in bloodstream and procyclic forms of Trypanosoma brucei, including the
      genome strain TREU927/4. We validate these cell lines using a variety of
      inducible experiments that recapture previously published lethal and non-lethal
      phenotypes. We further demonstrate the utility of the single marker (SmOx)
      TREU927/4 cell line for in vivo experiments in the tsetse fly and provide a set
      of plasmids that enable both whole-fly and salivary gland-specific inducible
      expression of transgenes.

PMID- 22645660
TI  - A brain-derived metric for preferred kinetic stimuli.
AB  - We here address the question of whether there is any correlation between
      subjective preference for simple configurations within a specific visual domain
      such as motion and strength of activity in visual areas in which that domain is
      emphasized. We prepared several distinctive patterns of dots in motion with
      various characteristics and asked humans to rate them according to their
      preference, before and while scanning the activity in their brains with
      functional magnetic resonance imaging. For simplicity, we restricted ourselves to
      motion in the fronto-parallel plane. Moving patterns produced activity in areas
      V1, V2, the V3 complex (V3, V3A, V3B) and V5, but only in areas V5, V3A/B and
      parietal cortex did the preferred kinetic patterns produce stronger activity when
      compared with the non-preferred ones. In addition, preferred patterns produced
      activity within field A1 of medial orbito-frontal cortex (mOFC), which is not
      otherwise activated by kinetic stimuli. Hence, for these areas, stronger neural
      activity correlated with subjective preference. We conclude that configurations
      of kinetic stimuli that are subjectively preferred correlate with stronger
      activity within early visual areas and within mOFC. This opens up the possibility
      of more detailed studies to relate subjective preferences to strength of activity
      in early visual areas and to relate activity in them to areas whose activity
      correlates with the subjective experience of beauty.

PMID- 22645662
TI  - Hexanucleotide motifs mediate recruitment of the RNA elimination machinery to
      silent meiotic genes.
AB  - The selective elimination system blocks the accumulation of meiosis-specific
      mRNAs during the mitotic cell cycle in fission yeast. These mRNAs harbour a
      region, the determinant of selective removal (DSR), which is recognized by a YTH
      family RNA-binding protein, Mmi1. Mmi1 directs target transcripts to destruction
      in association with nuclear exosomes. Hence, the interaction between DSR and Mmi1
      is crucial to discriminate mitosis from meiosis. Here, we show that Mmi1
      interacts with repeats of the hexanucleotide U(U/C)AAAC that are enriched in the
      DSR. Disruption of this 'DSR core motif' in a target mRNA inhibits its
      elimination. Tandem repeats of the motif can function as an artificial DSR. Mmi1
      binds to it in vitro. Thus, a core motif cluster is responsible for the DSR
      activity. Furthermore, certain variant hexanucleotide motifs can augment the
      function of the DSR core motif. Notably, meiRNA, which composes the nuclear Mei2
      dot required to suppress Mmi1 activity during meiosis, carries numerous copies of
      the core/augmenting motifs on its tail and is indeed degraded by the Mmi1/exosome
      system, indicating its likely role as decoy bait for Mmi1.

PMID- 22645664
TI  - Islet Transplantation & beta-Cell Replacement Therapies for Diabetes.

PMID- 22645663
TI  - Structure and function of FusB: an elongation factor G-binding fusidic acid
      resistance protein active in ribosomal translocation and recycling.
AB  - Fusidic acid (FA) is a bacteriostatic antibiotic that locks elongation factor G
      (EF-G) to the ribosome after GTP hydrolysis during elongation and ribosome
      recycling. The plasmid pUB101-encoded protein FusB causes FA resistance in
      clinical isolates of Staphylococcus aureus through an interaction with EF-G.
      Here, we report 1.6 and 2.3 A crystal structures of FusB. We show that FusB is a
      two-domain protein lacking homology to known structures, where the N-terminal
      domain is a four-helix bundle and the C-terminal domain has an alpha/beta fold
      containing a C4 treble clef zinc finger motif and two loop regions with conserved
      basic residues. Using hybrid constructs between S. aureus EF-G that binds to FusB
      and Escherichia coli EF-G that does not, we show that the sequence determinants
      for FusB recognition reside in domain IV and involve the C-terminal helix of S.
      aureus EF-G. Further, using kinetic assays in a reconstituted translation system,
      we demonstrate that FusB can rescue FA inhibition of tRNA translocation as well
      as ribosome recycling. We propose that FusB rescues S. aureus from FA inhibition
      by preventing formation or facilitating dissociation of the FA-locked EF-G
      ribosome complex.

PMID- 22645665
TI  - Medical gases: a novel strategy for attenuating ischemia-reperfusion injury in
      organ transplantation?
AB  - Ischemia reperfusion injury (IRI) is an inevitable clinical consequence in organ
      transplantation. It can lead to early graft nonfunction and contribute to acute
      and chronic graft rejection. Advanced molecular biology has revealed the highly
      complex nature of this phenomenon and few definitive therapies exist. This paper
      reviews factors involved in the pathophysiology of IRI and potential ways to
      attenuate it. In recent years, inhaled nitric oxide, carbon monoxide, and
      hydrogen sulfide have been increasingly explored as plausible novel medical gases
      that can attenuate IRI via multiple mechanisms, including microvascular
      vasorelaxation, reduced inflammation, and mitochondrial modulation. Here, we
      review recent advances in research utilizing inhaled nitric oxide, carbon
      monoxide, and hydrogen sulfide in animal and human studies of IRI and postulate
      on its future applications specific to solid organ transplantation.

PMID- 22645666
TI  - The association of obesity with walking independent of knee pain: the multicenter
      osteoarthritis study.
AB  - Practice guidelines recommend addressing obesity for people with knee OA,
      however, the association of obesity with walking independent of pain is not
      known. We investigated this association within the Multicenter Osteoarthritis
      Study, a cohort of older adults who have or are at high risk of knee OA. Subjects
      wore a StepWatch to record steps taken over 7 days. We measured knee pain from a
      visual analogue scale and obesity by BMI. We examined the association of obesity
      with walking using linear regression adjusting for pain and covariates. Of 1788
      subjects, the mean steps/day taken was 8872.9 +/- 3543.4. Subjects with a BMI
      >=35 took 3355 fewer steps per day independent of knee pain compared with those
      with a BMI <=25 (95% CI -3899, -2811). BMI accounted for 9.7% of the variability
      of walking while knee pain accounted for 2.9%. BMI was associated with walking
      independent of knee pain.

PMID- 22645668
TI  - Correlation of oxidative stress with serum trace element levels and antioxidant
      enzyme status in Beta thalassemia major patients: a review of the literature.
AB  - Beta thalassemia major is an inherited disease resulting from reduction or total
      lack of beta globin chains. Patients with this disease need repeated blood
      transfusion for survival. This may cause oxidative stress and tissue injury due
      to iron overload, altered antioxidant enzymes, and other essential trace element
      levels. The aim of this review is to scrutinize the relationship between
      oxidative stress and serum trace elements, degree of damage caused by oxidative
      stress, and the role of antioxidant enzymes in beta thalassemia major patients.
      The findings indicate that oxidative stress in patients with beta thalassemia
      major is mainly caused by tissue injury due to over production of free radical by
      secondary iron overload, alteration in serum trace elements and antioxidant
      enzymes level. The role of trace elements like selenium, copper, iron, and zinc
      in beta thalassemia major patients reveals a significant change of these trace
      elements. Studies published on the status of antioxidant enzymes like catalase,
      superoxide dismutase, glutathione, and glutathione S-transferase in beta
      thalassemia patients also showed variable results. The administration of
      selective antioxidants along with essential trace elements and minerals to reduce
      the extent of oxidative damage and related complications in beta thalassemia
      major still need further evaluation.

PMID- 22645667
TI  - When things are not as they appear: assessing the adequacy of cluster
      randomization when outcome events are rare at baseline.
AB  - The present study randomly assigned 15 Bahamian elementary schools to one of
      three intervention conditions. To assess the adequacy of cluster randomization,
      we examined two concerns identified by the local research team: inequality of
      gender distribution and environmental risk among groups. Baseline significant
      differences in risk and protective behaviors were minimal. There were
      significantly more males in the intervention group. Males had higher rates of
      risk behavior at all assessments. Poor school performance was also higher among
      the intervention condition and was significantly associated with increased rates
      of many but not all risk behaviors. Prior to adjusting for gender and school
      performance, several risk behaviors appeared to be higher after intervention
      among intervention youth. Adjusting for gender and school performance eradicated
      the group differences in risk behavior rates. Results demonstrate the importance
      of adequate randomization where outcomes of interest are rare events at baseline
      or differ by gender and there is an unequal gender distribution and the
      importance of the local research team's knowledge of potential inequalities in
      environmental risk (i.e., school performance). Not considering such individual
      differences could impact the integrity of trial outcomes.

PMID- 22645669
TI  - Sonographic lobe localization of alveolar-interstitial syndrome in the critically
      ill.
AB  - Introduction. Fast and accurate diagnosis of alveolar-interstitial syndrome is of
      major importance in the critically ill. We evaluated the utility of lung
      ultrasound (US) in detecting and localizing alveolar-interstitial syndrome in
      respective pulmonary lobes as compared to computed tomography scans (CT).
      Methods. One hundred and seven critically ill patients participated in the study.
      The presence of diffuse comet-tail artifacts was considered a sign of alveolar
      interstitial syndrome. We designated lobar reflections along intercostal spaces
      and surface lines by means of sonoanatomy in an effort to accurately localize
      lung pathology. Each sonographic finding was thereafter grouped into the
      respective lobe. Results. From 107 patients, 77 were finally included in the
      analysis (42 males with mean age = 61 +/- 17 years, APACHE II score = 17.6 +/-
      6.4, and lung injury score = 1.0 +/- 0.7). US exhibited high sensitivity and
      specificity values (ranging from over 80% for the lower lung fields up to over
      90% for the upper lung fields) and considerable consistency in the diagnosis and
      localization of alveolar-interstitial syndrome. Conclusions. US is a reliable,
      bedside method for accurate detection and localization of alveolar-interstitial
      syndrome in the critically ill.

PMID- 22645670
TI  - Change in Ratio of Observed-to-Expected Deaths in Pediatric Patients after
      Implementing a Closed Policy in an Adult ICU That Admits Children.
AB  - Backgrounds. We examined the effect on the prognosis of critically ill pediatric
      patients after a closed ICU policy was implemented into an adult ICU that
      admitted children. Materials and Methods. We assessed the Pediatric Index of
      Mortality 2 (PIM2) score of pediatric patients (<=15 y.o.) admitted to the ICU
      from 2001 to 2009. In our teaching hospital, the department for intensive care
      was established in January 2004. Since then, for critical care patients, we have
      followed a closed ICU policy with full-time intensivists. We subsequently
      compared PIM2 scores and the ratio of observed-to-expected deaths (O/E ratio) for
      three three-year periods: 2001-2003 (before closed policy), 2004-2006, and 2007
      2009. Results. Data was collected from 532 pediatric patients. While the PIM2
      score statistically significantly increased from 0.066 +/- 0.130 for 2001-2003 to
      0.114 +/- 0.239 for 2004-2006 and 0.086 +/- 0.147 for 2007-2009, the O/E ratio
      decreased from 1.49 for 2001-2003 to 0.82 for 2004-2006 and remained at 0.82 for
      2007-2009. Conclusion. The O/E ratio for critically ill pediatric patients
      improved after the establishment of a closed policy in an adult ICU that admitted
      children.

PMID- 22645671
TI  - Relationships between Depression and High Intellectual Potential.
AB  - This paper proposes to analyse the relationships between depression and high
      intellectual potential through a multidisciplinary and original approach. Based
      on their respective experience in psychology and child psychiatry, the authors
      will focus their analysis on creative potential. First, relationships between
      creativity (literary, artistic, or scientific creativity) and melancholy
      ("melancholy" comes from the Greek words for "black" ("melas") and "bile"
      ("khole")) will be examined from antiquity to modern times. Aristotle introduced
      a quantitative factor, asserting that levels of melancholy and black bile are
      positively correlated; however, under a given threshold of black bile, it can
      give rise to an exceptional being. Second, the case study of Blaise Pascal
      (scientific and philosophical creativity associated with major depressive
      episodes from childhood) will be presented and discussed. This case study sheds
      light on the paradoxical role of depression in the overinvestment in intellectual
      and creative spheres as well as on the impact of traumatic events on high
      intellectual potential. Third, observations will be reported based on a study
      conducted on 100 children with high intellectual potential (6-12 years old).
      Finally, based on these different levels of analysis, it appears that
      heterogeneity of mental functioning in children with high intellectual potential
      is at the center of the creative process and it has related psychological
      vulnerability.

PMID- 22645672
TI  - Additional gastrectomy after endoscopic submucosal dissection for early gastric
      cancer patients with comorbidities.
AB  - Purpose. We investigated the clinicopathologic features of early gastric cancer
      (EGC) patients who have undergone additional gastrectomy after endoscopic
      submucosal dissection (ESD) because of their comorbidities. Methods. Eighteen
      (7.1%) of 252 GC patients were gastrectomized after prior ESD. Reasons for
      further surgery, preoperative and postoperative problems, and the clinical
      outcome were determined. Results. The 18 patients had submucosal EGC and several
      co-morbidities. Other primary cancers were observed in 8 (44.4%). Histories of
      major abdominal operations were observed in 6 (33.3%). Fourteen patients (77.8%)
      hoped for endoscopic treatment. Due to additional gastrectomy, residual cancer
      was suspected in 10, and node metastasis was suspected in 11. A cancer remnant
      was histologically observed in one. Node metastasis was detected in 3 (16.7%).
      Small EGC was newly detected in 4. Consequently, additional gastrectomy was
      necessary for the one third. No patient showed GC recurrence. However, 9 (50%)
      had new diseases, and 4 (22.2%) died of other diseases. The overall survival
      after surgery in these patients with additional gastrectomy was poorer than those
      with routine gastrectomy for submucosal EGC (P = 0.0087). Conclusions. Additional
      gastrectomy was safely performed in EGC patients with co-morbidities. However,
      some issues, including presence of node metastasis and other death after surgery,
      remain.

PMID- 22645673
TI  - The effect of mentoring on career satisfaction of registered nurses and intent to
      stay in the nursing profession.
AB  - Mentoring is important in the career development of novice and experienced
      nurses. With the anticipated shortage in nursing, it is important to explore
      factors such as mentoring that may contribute to career satisfaction and intent
      to stay in the profession. This study explored the effects of mentoring on career
      satisfaction and intent to stay in nursing, and the relationship between career
      satisfaction and intent to stay in nursing. It was conducted through a mailed
      survey of RNs 55 years or younger currently in practice, education,
      administration, or research. Career satisfaction was measured through the use of
      the newly developed Mariani Nursing Career Satisfaction Scale. Findings revealed
      no statistically significant effect of mentoring on career satisfaction and
      intent to stay in nursing. There was a statistically significant relationship
      between career satisfaction and intent to stay in nursing. The majority of nurses
      reported participating in a mentoring relationship. Although the findings related
      to mentoring, career satisfaction, and intent to stay were not statistically
      significant, there was a prevalence of mentoring in nursing, thus suggesting the
      need for future research to identify outcomes of mentoring. In addition, the
      study contributed a newly developed instrument to measure the concept of career
      satisfaction in nursing.

PMID- 22645674
TI  - Stakeholder focus groups to inform a technology-based strategy of preceptor
      support.
AB  - While preceptors are a vital link in student nurse practice education, ongoing
      support beyond an initial orientation is often lacking. It has been reported in
      the literature that preceptors experience stress related to difficulties in
      handling preceptee situations. They are frustrated by negative experiences
      centered on preceptor-identified hallmarks of unsafe practice including the
      inability to demonstrate knowledge and skills; attitude problems; unprofessional
      behavior; and poor communication skills. Their unrealized expectations for
      novices threaten their commitment to their preceptor role. As part of a larger
      study testing the effectiveness of podcasts as an ongoing method of preceptor
      support, this paper addresses the developmental stage of the podcasts. A team of
      academic and acute care nurse educators developed scripts for eventual filming of
      four podcasts focusing on unsafe practice issues, designed to provide continual
      support through web-based availability. The use of podcast technology is
      consistent with the learning styles of digital natives and is a demonstrated and
      valuable educational resource to review, reinforce, and clarify difficult
      concepts. These podcasts were informed through preceptor focus groups to address
      situational and environmental realism for student behaviors and preceptor
      responses.

PMID- 22645675
TI  - Single-port laparascopic cholecystectomy: scarless cholecystectomy.
AB  - Objective. Single-incision laparoscopic surgery is a new advanced technology to
      further minimize the invasiveness of laparoscopy through a single small incision
      hidden in the umbilicus. The objective is to describe short and long-term
      outcomes of SILS cholecystectomy. Methodology. Patients with gallbladder
      pathologies were unselectively enrolled and were prospectively studied between
      April 2009 and April 2010 and completed a post-operative follow-up for 12 months.
      Results. There were 22 women and 8 men. Mean age was 46 years. Twenty-one
      patients had biliary colic, seven had acute cholecystitis, one had gallbladder
      polyp, and another had resolving acute pancreatitis. Mean operative time was
      104.3 +/- 44 minutes. Mean BMI was 30.42 and the average pain score was 3.2 +/-
      1.1. One more port was inserted to help in finishing the procedure in one
      patient. There was no conversion to a standard laparoscopic or open technique.
      There was one post-operative bile collection from a missed cyctic duct of
      Luschka. Mean hospital stay was 1.2 days. Conclusion. Single-port laparoscopic
      cholecystectomy is feasible. Early conversion to a standard laparoscopic
      technique is advised to avoid serious complications. The procedure has an obvious
      cosmetic benefit. Additional prospective trials are necessary to define the
      benefits of single-port laparoscopic cholecystectomy.

PMID- 22645676
TI  - Objective assessment of the core laparoscopic skills course.
AB  - Objective. The demand for laparoscopic surgery has led to the core laparoscopic
      skills course (CLSC) becoming mandatory for trainees in UK. Virtual reality
      simulation (VR) has a great potential as a training and assessment tool of
      laparoscopic skills. The aim of this study was to determine the role of the CLSC
      in developing laparoscopic skills using the VR. Design. Prospective study.
      Doctors were given teaching to explain how to perform PEG transfer and clipping
      skills using the VR. They carried out these skills before and after the course.
      During the course they were trained using the Box Trainer (BT). Certain
      parameters assessed. Setting. Between 2008 and 2010, doctors attending the CLSC
      at St Georges Hospital. Participants. All doctors with minimal laparoscopic
      experience attending the CLSC. Results. Forty eight doctors were included. The
      time taken for the PEG skill improved by 52%, total left hand and right hand
      length by 41% and 48%. The total time in the clipping skill improved by 57%.
      Improvement in clips applied in the marked area was 38% and 45% in maximum vessel
      stretch. Conclusions. This study demonstrated that CLSC improved some aspects of
      the laparoscopic surgical skills. It addresses Practice-based Learning and
      patient care.

PMID- 22645677
TI  - Bariatric surgery in the Caribbean: is it safe in a low-volume, third world
      setting?
AB  - Bariatric surgery is a well-recognized modality of management of obesity. In
      addition to obesity, it effectively controls diabetes mellitus, and hypertension.
      It has been recommended that bariatric surgery should be done in "designated
      centers" of excellence where there is a high volume of case turnover. Caribbean
      nations are not spared from the global spread of the obesity epidemic; however,
      not many patients get the benefits of bariatric surgery. This study aimed to
      establish that bariatric surgery could be safely and efficiently undertaken in a
      low-volume center outside the "designated centers" with comparable patient
      outcomes even in a third world setting. Though "patient numbers" generally imply
      better outcome, in an environment where these numbers cannot be achieved,
      patients should not be denied the access to surgery once good outcomes are
      achieved.

PMID- 22645678
TI  - Dabigatran for stroke prevention in nonvalvular atrial fibrillation: answers to
      challenging "real-world" questions.
AB  - Dabigatran etexilate is a novel, oral, reversible, direct thrombin inhibitor that
      constitutes a major breakthrough for stroke prevention in patients with
      nonvalvular atrial fibrillation (AF). Dabigatran was the first new oral
      anticoagulant approved in Europe and became available in Portugal, for stroke
      prevention in nonvalvular AF, earlier than in most European countries. This paper
      is the joint effort of a panel of experts from different specialties and provides
      information on the use of dabigatran, in anticipation of the challenges that will
      come with increased usage.

PMID- 22645679
TI  - A Quantitative Examination of Extreme Facial Pain Expression in Neonates: The
      Primal Face of Pain across Time.
AB  - Many pain assessment tools for preschool and school-aged children are based on
      facial expressions of pain. Despite broad use, their metrics are not rooted in
      the anatomic display of the facial pain expression. We aim to describe
      quantitatively the patterns of initiation and maintenance of the infant pain
      expression across an expressive cycle. We evaluated the trajectory of the pain
      expression of three newborns with the most intense facial display among 63
      infants receiving a painful stimulus. A modified "point-pair" system was used to
      measure movement in key areas across the face by analyzing still pictures from
      video recording the procedure. Point-pairs were combined into "upper face" and
      "lower face" variables; duration and intensity of expression were standardized.
      Intensity and duration of expression varied among infants. Upper and lower face
      movement rose and overlapped in intensity about 30% into the expression. The
      expression reached plateau without major change for the duration of the
      expressive cycle. We conclude that there appears to be a shared pattern in the
      dynamic trajectory of the pain display among infants expressing extreme
      intensity. We speculate that these patterns are important in the communication of
      pain, and their incorporation in facial pain scales may improve current metrics.

PMID- 22645680
TI  - Intravascular Talcosis due to Intravenous Drug Use Is an Underrecognized Cause of
      Pulmonary Hypertension.
AB  - Intravenous injection of illegal drugs or medications meant for oral
      administration can cause granulomatous disease of the lung. This intravascular
      talcosis results in pulmonary fibrosis and pulmonary hypertension. Nine cases of
      histologically confirmed intravascular talcosis were reviewed with specific
      attention given to the clinical histories in these patients. Five autopsy cases
      were included in this series with detailed investigation in the anatomic features
      associated with intravascular talcosis and pulmonary hypertension. All nine
      patients showed perivascular and/or intravascular deposition of polarizable
      foreign material in their lungs. Intravascular talcosis as a result of previous
      intravenous drug use was not clinically suspected in any patient despite
      clinically diagnosed pulmonary hypertension in five. All patients showed
      dilatation of the right and left heart, but none had dilatation of the aortic
      valve. Congestive heart failure with hepatosplenomegaly was also common. We
      conclude that intravascular talcosis is an underdiagnosed cause of pulmonary
      hypertension in patients with known history of intravenous drug use.

PMID- 22645681
TI  - From genetics to genomics of epilepsy.
AB  - The introduction of DNA microarrays and DNA sequencing technologies in medical
      genetics and diagnostics has been a challenge that has significantly transformed
      medical practice and patient management. Because of the great advancements in
      molecular genetics and the development of simple laboratory technology to
      identify the mutations in the causative genes, also the diagnostic approach to
      epilepsy has significantly changed. However, the clinical use of molecular
      cytogenetics and high-throughput DNA sequencing technologies, which are able to
      test an entire genome for genetic variants that are associated with the disease,
      is preparing a further revolution in the near future. Molecular Karyotype and
      Next-Generation Sequencing have the potential to identify causative genes or loci
      also in sporadic or non-familial epilepsy cases and may well represent the
      transition from a genetic to a genomic approach to epilepsy.

PMID- 22645682
TI  - Activation of Right Ventral Prefrontal Cortex Using a Predictive Cue during
      Visual Spatial Orienting of Attentional Processes: An fMRI Study.
AB  - Visual spatial orienting of attention can be investigated with location-cueing
      paradigms in which a cue provides correct information about the location of the
      upcoming target. Target detection is facilitated when the target appears at the
      expected cued location. In this study, we examined the brain activation of the
      spatial orienting response based on attentional "benefits." During an fMRI
      experiment, two types of attentional tasks were used. Both predictive and
      nonpredictive cues were used and followed by an upcoming target. Behavioral data
      showed a faster reaction time with the predictive cue when compared with that of
      the nonpredictive cue. The fMRI results of these two tasks were compared, whereby
      isolated brain areas activated when the targets appeared at the attended position
      after a specific spatial expectation was induced by the cue were compared with
      when equivalent targets appeared after no spatial expectation was induced by the
      cue. The results showed that the right ventral prefrontal cortex was activated to
      a similar degree as the dorsal frontoparietal spatial attentional network.

PMID- 22645684
TI  - Strength-duration time constant in peripheral nerve: no abnormality in multiple
      sclerosis.
AB  - Objectives. To investigate the properties of the strength-duration time constant
      (SDTC) in multiple sclerosis (MS) patients. Methods. The SDTC and rheobase in 16
      MS patients and 19 healthy controls were obtained following stimulation of the
      right median nerve at the wrist. Results. SDTC and rheobase values were 408.3 +/-
      60.0 MUs and 4.0 +/- 1.8 mA in MS patients, versus 408.0 +/- 62.4 MUs and 3.8 +/-
      2.1 mA in controls. The differences were not significant in SDTC or rheobase
      values between the patients and controls (P = 0.988 for SDTC and P = 0.722 for
      rheobase). Conclusion. Our study showed no abnormality in relapsing remitting MS
      patients in terms of SDTC, which gives some indirect information about peripheral
      Na(+) channel function. This may indicate that alterations in the Na(+) channel
      pattern in central nervous system (CNS) couldnot be shown in the peripheral
      nervous system (PNS) in the MS patients by SDTC. The opinion that MS can be a
      kind of channelopathy might be proven by performing other axonal excitability
      tests or SDTC in progressive forms of MS.

PMID- 22645683
TI  - Urinary markers of glomerular injury in diabetic nephropathy.
AB  - Diabetic nephropathy, the leading cause of renal failure worldwide, affects
      approximately one-third of all people with diabetes. Microalbuminuria is
      considered the first sign and the best predictor of progression to renal failure
      and cardiovascular events. However, albuminuria has several limitations.
      Therefore, earlier, more sensitive and specific biomarkers with greater
      predictability are needed. The aim of this paper is to discuss the current
      literature on biomarkers of glomerular injury that have been implicated in
      diabetic kidney disease.

PMID- 22645685
TI  - Effectiveness of the gaze direction recognition task for chronic neck pain and
      cervical range of motion: a randomized controlled pilot study.
AB  - We developed a mental task with gaze direction recognition (GDR) by which
      subjects observed neck rotation of another individual from behind and attempted
      to recognize the direction of gaze. A randomized controlled trial was performed
      in test (n = 9) and control (n = 8) groups of subjects with chronic neck pain
      undergoing physical therapy either with or without the GDR task carried out over
      12 sessions during a three-week period. Primary outcome measures were defined as
      the active range of motion and pain on rotation of the neck. Secondary outcome
      measures were reaction time (RT) and response accuracy in the GDR task group.
      ANOVA indicated a main effect for task session and group, and interaction of
      session. Post hoc testing showed that the GDR task group exhibited a significant
      simple main effect upon session, and significant sequential improvement of neck
      motion and relief of neck pain. Rapid effectiveness was significant in both
      groups. The GDR task group had a significant session-to-session reduction of RTs
      in correct responses. In conclusion, the GDR task we developed provides a
      promising rehabilitation measure for chronic neck pain.

PMID- 22645687
TI  - Outcome for patients with triple-negative breast cancer is not dependent on
      race/ethnicity.
AB  - Introduction. Triple negative breast cancer (TNBC) is biologically aggressive and
      is associated with a worse prognosis. To understand the impact of race/ethnicity
      on outcome for patients with TNBC, confounding factors such as socioeconomic
      status (SES) need to be controlled. We examined the impact of race/ethnicity on a
      cohort of patients of low SES who have TNBC. Methods. 786 patients with Stage 0
      III breast cancer were evaluated. Of these, 202 patients had TNBC (26%). Primary
      endpoints were cancer recurrence and death. ZIP code-based income tract and
      institutional financial data were used to assess SES. Data were analyzed using
      Kaplan-Meier survival analysis, log-rank tests, Cox Proportional hazard
      regression, chi square test, and t-tests. A P value <=0.05 was considered
      statistically significant. Results. Of the 468 African-Americans (60%) in the
      database, 138 had TNBC; 64 of 318 Caucasians had TNBC. 80% of patients had an
      annual income of <=$20,000. The 5-year overall survival was 77% for African
      American women versus 72% for Caucasian women (P = 0.95). On multivariate
      analysis, race/ethnicity had an impact on disease-free survival (P = 0.027) but
      not on overall survival (P = 0.98). Conclusion. In a predominantly indigent
      population, race/ethnicity had no impact on overall survival for patients with
      triple negative breast cancer.

PMID- 22645686
TI  - Poly(ethylene glycol)-Prodrug Conjugates: Concept, Design, and Applications.
AB  - Poly(ethylene glycol) (PEG) is the most widely used polymer in delivering
      anticancer drugs clinically. PEGylation (i.e., the covalent attachment of PEG) of
      peptides proteins, drugs, and bioactives is known to enhance the aqueous
      solubility of hydrophobic drugs, prolong circulation time, minimize nonspecific
      uptake, and achieve specific tumor targetability through the enhanced
      permeability and retention effect. Numerous PEG-based therapeutics have been
      developed, and several have received market approval. A vast amount of clinical
      experience has been gained which has helped to design PEG prodrug conjugates with
      improved therapeutic efficacy and reduced systemic toxicity. However, more
      efforts in designing PEG-based prodrug conjugates are anticipated. In light of
      this, the current paper highlights the synthetic advances in PEG prodrug
      conjugation methodologies with varied bioactive components of clinical relevance.
      In addition, this paper discusses FDA-approved PEGylated delivery systems, their
      intended clinical applications, and formulations under clinical trials.

PMID- 22645688
TI  - Tissue reactions to various suture materials used in oral surgical interventions.
AB  - A variety of suture materials are available for primary wound closure following
      oral surgical procedures. The aim was to review the tissue reactions to the
      various suture materials used in oral surgical interventions. Databases were
      searched using the following keywords: cotton, nylon, polyglecaprone 25,
      polytetrafluoroethylene (ePTFE), Polyglactin 910, polyglycolic acid (PGA),
      polylactic acid, silk, surgery, suture, and tissue reaction. Articles published
      only in English language were included. Seventeen studies were included. Two
      studies reported that polyglecaprone 25 had positive effects on wound-healing as
      compared to silk. Six studies reported that silk elicits more intense tissue
      inflammatory response and delayed wound healing as compared to other suture
      materials (including ePTFE, polyglecaprone-25, PGA, and nylon). Polyglactin 910
      sutures were associated with the development of stitch abscess in one clinical
      study. Eight studies reported that tissue reactions are minimal with nylon
      sutures. Tissue reactions to suture materials used for oral surgical
      interventions may vary depending on the surface properties and bacterial
      adherence properties of the material.

PMID- 22645689
TI  - The management of type 2 diabetic patients with hypoglycaemic agents.
AB  - Type 2 Diabetes Mellitus (T2DM) is characterized by chronic hyperglycemia with
      disturbance in carbohydrate, lipid, and protein metabolism due to insulin
      resistance and beta cell dysfunction. Epidemiological studies have confirmed a
      global pandemic of T2DM, which has created an enormous burden on society, with
      regard to morbidity, mortality, and health care expenditures. Life style
      modifications are fundamental not only in early stages of disease management but
      need to be intensified as disease progresses. United Kingdom Prospective Diabetes
      Study (UKPDS) has demonstrated the progressive nature of T2DM, and as disease
      progresses, a combination agents-oral antidiabetic drugs (OAD) and insulin-are
      needed in order to maintain good sugar control. The general consensus of HbA1c
      target for most patients is less than 7%, and various guidelines and algorithms
      have provided guidance in patient management to keep patient at goal. As our
      understanding of pathophysiological defects advances, targeting treatment at
      underlying defects not only enables us to achieve HbA1c goal but also reduces
      morbidities, mortalities, and progression of the disease. Traditional oral agents
      like metformin and sulfonylureas have failed to arrest the progression of T2DM.
      New agents such as TZD, DPP-4 inhibitor, and SGLT-2 may increase our
      armamentariums against T2DM.

PMID- 22645690
TI  - Abnormal Movements of Japanese Infants following Treatment with Midazolam in a
      Neonatal Intensive Care Unit: Incidence and Risk Factors.
AB  - Background. This study was conducted to investigate the incidence of, and factors
      associated with, myoclonus-like abnormal movements of Japanese infants following
      treatment with midazolam in a neonatal intensive care unit (NICU). Methods. We
      retrospectively investigated abnormal movements and associated risk factors in
      Japanese infants (less than 1 year old) who received continuous intravenous
      midazolam treatment in the NICU of the Neonatal Medical Center, Kumamoto City
      Hospital, Japan, between April 2007 and March 2009. Results. The study included
      94 infants who received 119 sessions of midazolam treatment in total. Nine
      infants (9.6%) developed abnormal movements attributable to midazolam. These nine
      patients had a significantly lower gestational age at birth, a significantly
      lower number of weeks after conception at the start of midazolam treatment, and
      significantly lower body weight compared with patients free of abnormal
      movements. Logistic regression analysis revealed neonatal asphyxia as a factor
      associated with an elevated risk of abnormal movements (P = 0.03). Conclusion.
      The incidence of abnormal movements after midazolam treatment was about 9.6%
      among the Japanese NICU infants. This result suggests that neonatal asphyxia may
      be involved in the onset of abnormal movements in infants treated with midazolam.

PMID- 22645691
TI  - (99m)Tc-DMSA (V) in Evaluation of Osteosarcoma: Comparative Studies with (18)F
      FDG PET/CT in Detection of Primary and Malignant Lesions.
AB  - To evaluate the role of (99m)Tc-DMSA (V) and [(18)F]FDG PET-CT in management of
      patients with osteosarcoma, 22 patients were included in our study. All patients
      underwent both (99m)Tc-DMSA (V) and whole-body [(18)F]FDG PET-CT scans within an
      interval of 1 week. 555-740 MBq of (99m)Tc-DMSA (V) was injected i.v. the whole
      body planar, SPECT images of primary site and chest were performed after 3-4
      hours. [(18)F]FDG PET-CT images were obtained 60 minutes after i.v. injection of
      370 MBq of F-18 FDG. Both FDG PET-CT (mean SUV(max) = 7.1) and DMSA (V) scans
      showed abnormal uptake at primary site in all the 22 patients (100% sensitivity
      for both). Whole-body PET-CT detected metastasis in 11 pts (lung mets in 10 and
      lung + bone mets in 1 patient). Whole-body planar DMSA (V) and SPECT detected
      bone metastasis in one patient, lung mets in 7 patients and LN in 1 patient. HRCT
      of chest confirmed lung mets in 10 patients and inflammatory lesion in one
      patient. 7 patients positive for mets on DMSA (V) scan had higher uptake in lung
      lesions as compared to FDG uptake on PET-CT. Three patients who did not show any
      DMSA uptake had subcentimeter lung nodule. Resuts of both (99m)Tc-DMSA (V) (whole
      body planar and SPECT imaging) and [(18)F]FDG PET-CT were comparable in
      evaluation of primary site lesions and metastatic lesions greater than 1 cm.
      Though (99m)Tc-DMSA (V) had higher uptake in the lesions as compared to
      [(18)F]FDG PET-CT, the only advantage [(18)F]FDG PET-CT had was that it could
      also detect subcentimeter lesions.

PMID- 22645692
TI  - Hippocampal dendritic spines modifications induced by perinatal asphyxia.
AB  - Perinatal asphyxia (PA) affects the synaptic function and morphological
      organization. In previous works, we have shown neuronal and synaptic changes in
      rat neostriatum subjected to hypoxia leading to long-term ubi-protein
      accumulation. Since F-actin is highly concentrated in dendritic spines,
      modifications in its organization could be related with alterations induced by
      hypoxia in the central nervous system (CNS). In the present study, we investigate
      the effects of PA on the actin cytoskeleton of hippocampal postsynaptic densities
      (PSD) in 4-month-old rats. PSD showed an increment in their thickness and in the
      level of ubiquitination. Correlative fluorescence-electron microscopy
      photooxidation showed a decrease in the number of F-actin-stained spines in
      hippocampal excitatory synapses subjected to PA. Although western blot analysis
      also showed a slight decrease in beta-actin in PSD in PA animals, the difference
      was not significant. Taken together, this data suggests that long-term actin
      cytoskeleton might have role in PSD alterations which would be a spread
      phenomenon induced by PA.

PMID- 22645693
TI  - Growing teratoma syndrome: a rare case report and review of the literature.
AB  - Growing teratoma syndrome is rare and usually it occurs in the younger aged
      group. The use of chemotherapy following initial surgical resection will yield
      the diagnosis following tumour enlargement. Complete resection is usually
      curative and renders better prognosis.

PMID- 22645696
TI  - Association of Self-Reported Weight Change and Quality of Life, and Exercise and
      Weight Management Behaviors Among Adults with Type 2 Diabetes Mellitus: The
      SHIELD Study.
AB  - Purpose. This study examined the association between self-reported weight change
      and quality of life, and exercise and weight management behaviors among
      individuals with type 2 diabetes mellitus (T2DM). Methods. In the US SHIELD
      study, respondents reported whether they had lost or gained weight compared with
      1 year earlier and completed the SHIELD-WQ-9 quality of life questionnaire as
      well as provided information on their exercise and weight management behaviors in
      the past 12 months. Results. Sixteen percent of the respondents reported gaining
      weight (n = 460), and 30% reported losing weight (n = 895). More respondents who
      reported losing weight exercised regularly, limited calorie and fat intake, and
      increased fiber, fruit, and vegetable intake compared with respondents who
      reported gaining weight (P < 0.01). For all nine aspects of daily life, a
      significantly greater proportion of respondents who reported losing weight
      reported improved well-being (12%-44%) compared with respondents who reported
      gaining weight (P < 0.0001). Conclusions. Self-reported weight loss was
      associated with improved well-being, better exercise, and weight management
      behaviors among individuals with T2DM.

PMID- 22645695
TI  - Diverse spectrum of presentation of coronary slow flow phenomenon: a concise
      review of the literature.
AB  - The coronary slow flow phenomenon (CSFP) is a disease entity characterized by
      slow progression of angiographic contrast in the coronary arteries in the absence
      of stenosis in the epicardial vessels. CSFP has a diverse presentation from mild
      chest discomfort to ST-segment elevation myocardial infarction. It can also have
      severe morbidity and mortality implications and can significantly hamper the
      quality of life of those affected. In this paper we present two patients with
      CSFP highlighting the diverse spectrum of presentation. A concise review of the
      literature is also provided emphasizing the epidemiology, pathogenesis,
      diagnostic parameters, treatment modalities, and clinical significance of this
      phenomenon.

PMID- 22645694
TI  - Targeted In Situ Gene Correction of Dysfunctional APOE Alleles to Produce
      Atheroprotective Plasma ApoE3 Protein.
AB  - Cardiovascular disease is the leading worldwide cause of death. Apolipoprotein E
      (ApoE) is a 34-kDa circulating glycoprotein, secreted by the liver and
      macrophages with pleiotropic antiatherogenic functions and hence a candidate to
      treat hypercholesterolaemia and atherosclerosis. Here, we describe
      atheroprotective properties of ApoE, though also potential proatherogenic
      actions, and the prevalence of dysfunctional isoforms, outline conventional gene
      transfer strategies, and then focus on gene correction therapeutics that can
      repair defective APOE alleles. In particular, we discuss the possibility and
      potential benefit of applying in combination two technical advances to repair
      aberrant APOE genes: (i) an engineered endonuclease to introduce a double-strand
      break (DSB) in exon 4, which contains the common, but dysfunctional, epsilon2 and
      epsilon4 alleles; (ii) an efficient and selectable template for homologous
      recombination (HR) repair, namely, an adeno-associated viral (AAV) vector, which
      harbours wild-type APOE sequence. This technology is applicable ex vivo, for
      example to target haematopoietic or induced pluripotent stem cells, and also for
      in vivo hepatic gene targeting. It is to be hoped that such emerging technology
      will eventually translate to patient therapy to reduce CVD risk.

PMID- 22645698
TI  - The Relationship between Different Assays for Detection and Quantification of
      Amyloid Beta 42 in Human Cerebrospinal Fluid.
AB  - Alzheimer's disease (AD), which is characterized by a degeneration of neurons and
      their synapses, is one of the most common forms of dementia. CSF levels of
      amyloid beta(42) (Abeta(42)) have been recognized as a strong candidate to serve
      as an AD biomarker. There are a number of commercial assays that are routinely
      employed for measuring Abeta(42); however, these assays give diverse ranges for
      the absolute levels of CSF Abeta(42). In order to employ CSF Abeta(42) as a
      biomarker across multiple laboratories, studies need to be performed to
      understand the relationship between the different platforms. We have analyzed CSF
      samples from both diseased and nondiseased subjects with two different widely
      used assay platforms. The results showed that different values for the levels of
      CSF Abeta(42) were reported, depending on the assay used. Nonetheless, both
      assays clearly demonstrated statistically significant differences in the levels
      of Abeta(42) in CSF from AD relative to age-matched controls (AMC). This paper
      provides essential data for establishing the relationship between these assays
      and provides an important step towards the validation of Abeta(42) as a biomarker
      for AD.

PMID- 22645697
TI  - Microglial Amyloid-beta1-40 Phagocytosis Dysfunction Is Caused by High-Mobility
      Group Box Protein-1: Implications for the Pathological Progression of Alzheimer's
      Disease.
AB  - In Alzheimer disease (AD) patient brains, the accumulation of amyloid-beta
      (Abeta) peptides is associated with activated microglia. Abeta is derived from
      the amyloid precursor protein; two major forms of Abeta, that is, Abeta1-40
      (Abeta40) and Abeta1-42 (Abeta42), exist. We previously reported that rat
      microglia phagocytose Abeta42, and high mobility group box protein 1 (HMGB1), a
      chromosomal protein, inhibits phagocytosis. In the present study, we investigated
      the effects of exogenous HMGB1 on rat microglial Abeta40 phagocytosis. In the
      presence of exogenous HMGB1, Abeta40 markedly increased in microglial cytoplasm,
      and the reduction of extracellular Abeta40 was inhibited. During this period,
      HMGB1 was colocalized with Abeta40 in the cytoplasm. Furthermore, exogenous HMGB1
      inhibited the degradation of Abeta40 induced by the rat microglial cytosolic
      fraction. Thus, extracellular HMGB1 may internalize with Abeta40 in the
      microglial cytoplasm and inhibit Abeta40 degradation by microglia. This may
      subsequently delay Abeta40 clearance. We further confirmed that in AD brains, the
      parts of senile plaques surrounded by activated microglia are composed of
      Abeta40, and extracellular HMGB1 is deposited on these plaques. Taken together,
      microglial Abeta phagocytosis dysfunction may be caused by HMGB1 that accumulates
      extracellularly on Abeta plaques, and it may be critically involved in the
      pathological progression of AD.

PMID- 22645699
TI  - Evolution of lysine biosynthesis in the phylum deinococcus-thermus.
AB  - Thermus thermophilus biosynthesizes lysine through the alpha-aminoadipate (AAA)
      pathway: this observation was the first discovery of lysine biosynthesis through
      the AAA pathway in archaea and bacteria. Genes homologous to the T. thermophilus
      lysine biosynthetic genes are widely distributed in bacteria of the Deinococcus
      Thermus phylum. Our phylogenetic analyses strongly suggest that a common ancestor
      of the Deinococcus-Thermus phylum had the ancestral genes for bacterial lysine
      biosynthesis through the AAA pathway. In addition, our findings suggest that the
      ancestor lacked genes for lysine biosynthesis through the diaminopimelate (DAP)
      pathway. Interestingly, Deinococcus proteolyticus does not have the genes for
      lysine biosynthesis through the AAA pathway but does have the genes for lysine
      biosynthesis through the DAP pathway. Phylogenetic analyses of D. proteolyticus
      lysine biosynthetic genes showed that the key gene cluster for the DAP pathway
      was transferred horizontally from a phylogenetically distant organism.

PMID- 22645700
TI  - Activated Protein C Does Not Alleviate the Course of Systemic Inflammation in the
      APCAP Trial.
AB  - The study aimed to determine the effect of the activated protein C on the course
      of systemic inflammation in the APCAP (activated protein C in acute pancreatitis)
      trial where we randomized 32 patients with severe acute pancreatitis to receive
      either recombinant activated protein C (drotrecogin alfa activated) (n = 16) or
      placebo (n = 16) for 96 hours. In the present study, we present the time course
      of the patients' plasma or serum levels of soluble markers (IL-8, IL-6, IL-10, IL
      1ra, sE-selectin, PCT) and monocyte and neutrophil cell surface (CD11b, CD14,
      CD62L, HLA-DR) markers of systemic inflammatory response during the first 14 days
      after the randomization. The results of the intervention and placebo groups were
      comparable showing that recombinant APC treatment did not alter the course of
      systemic inflammation in severe acute pancreatitis. Our finding is in accordance
      with the clinical findings in the APCAP trial indicating that the intervention
      did not affect evolution of multiple organ dysfunctions.

PMID- 22645701
TI  - Surgical Approach and Laser Applications in BRONJ Osteoporotic and Cancer
      Patients.
AB  - Bisphosphonates-related Osteonecrosis of the Jaw (BRONJ) has been reported with
      increasing frequency in literature over last years, but its therapy is still a
      dilemma. One hundred ninety patients affected by BRONJ were observed between
      January 2004 and November 2011 and 166 treated sites were subdivided in five
      groups on the basis of the therapeutical approach (medical or surgical,
      traditional or laser-assisted approach, with or without Low Level Laser Therapy
      (LLLT)). Clinical success has been defined for each treatment performed as
      clinical improvement or complete mucosal healing. Combination of antibiotic
      therapy, conservative surgery performed with Er:YAG laser and LLLT applications
      showed best results for cancer and noncancer patients. Nonsurgical approach
      performed on 69 sites induced an improvement in 35 sites (50.7%) and the complete
      healing in 19 sites (27.5%), while surgical approach on 97 sites induced an
      improvement in 84 sites (86.6%) and the complete healing in 78 sites (80.41%).
      Improvement and healing were recorded in 31 (81.5%) and 27 (71.5%) out of the 38
      BRONJ sites treated in noncancer patients and in 88 (68.75%) and in 69 (53.9%)
      out of the 128 in cancer patients.

PMID- 22645702
TI  - Recommendations for management of patients with carotid stenosis.
AB  - Stroke is a one of the leading causes of morbidity and mortality in the world.
      Carotid atherosclerosis is recognized as an important factor in stroke
      pathophysiology and represents a key target in stroke prevention; multiple
      treatment modalities have been developed to battle this disease. Multiple
      randomized trials have shown the efficacy of carotid endarterectomy in secondary
      stroke prevention. Carotid stenting, a newer treatment option, presents a less
      invasive alternative to the surgical intervention on carotid arteries. Advances
      in medical therapy have also enabled further risk reduction in the overall
      incidence of stroke. Despite numerous trials and decades of clinical research,
      the optimal management of symptomatic and asymptomatic carotid disease remains
      controversial. We will attempt to highlight some of the pivotal trials already
      completed, discuss the current controversies and complexities in the treatment
      decision-making, and postulate on what likely lies ahead. This paper will
      highlight the complexities of decision-making optimal treatment recommendations
      for patients with symptomatic and asymptomatic carotid stenosis.

PMID- 22645703
TI  - Racial differences by ischemic stroke subtype: a comprehensive diagnostic
      approach.
AB  - Background. Previous studies have suggested that black populations have more
      small-vessel and fewer cardioembolic strokes. We sought to analyze racial
      differences in ischemic stroke subtype employing a comprehensive diagnostic
      workup with magnetic resonance-imaging-(MRI-) based evaluation including
      diffusion-weighted imaging (DWI). Methods. 350 acute ischemic stroke patients
      admitted to an urban hospital with standardized comprehensive diagnostic
      evaluations were retrospectively analyzed. Ischemic stroke subtype was determined
      by three Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification
      systems. Results. We found similar proportions of cardioembolic and lacunar
      strokes in the black and white cohort. The only subtype category with a
      significant difference by race was "stroke of other etiology," more common in
      whites. Black stroke patients were more likely to have an incomplete evaluation,
      but this did not reach significance. Conclusions. We found similar proportions by
      race of cardioembolic and lacunar strokes when employing a full diagnostic
      evaluation including DWI MRI. The relatively high rate of cardioembolism may have
      been underappreciated in black stroke patients when employing a CT approach to
      stroke subtype diagnosis. Further research is required to better understand the
      racial differences in frequency of "stroke of other etiology" and explore
      disparities in the extent of diagnostic evaluations.

PMID- 22645704
TI  - A note from the Editor-in-Chief.

PMID- 22645706
TI  - Greasing the protein biosynthesis machinery of photoreceptor neurons: Role for
      postprenylation processing of proteins.
AB  - Daily phagocytosis of outer segments (OS) places extraordinary demands on protein
      biosynthesis and trafficking in photoreceptor neurons. While the members and
      roles of the phototransduction pathway in the OS are well characterized, details
      about protein trafficking are just beginning to emerge. Phosphodiesterase6
      (PDE6), the effector enzyme in phototransduction cascade, serves as an example of
      the steps multimeric proteins must pass through to achieve their functional state
      in the OS. Genetic model systems have recently provided snapshots of various
      steps in the pathway, as experimental difficulties such as an inability to
      maintain ciliated photoreceptor outer segments or express functional PDE6
      holoenzyme in vitro necessitate in vivo studies. We will highlight the
      significant findings, their implications to blinding diseases, as well as discuss
      the gaps requiring further investigation.

PMID- 22645705
TI  - Searching for gold beyond mitosis: Mining intracellular membrane traffic in
      Aspergillus nidulans.
AB  - The genetically tractable filamentous ascomycete fungus Aspergillus nidulans has
      been successfully exploited to gain major insight into the eukaryotic cell cycle.
      More recently, its amenability to in vivo multidimensional microscopy has fueled
      a potentially gilded second age of A. nidulans cell biology studies. This review
      specifically deals with studies on intracellular membrane traffic in A. nidulans.
      The cellular logistics are subordinated to the needs imposed by the polarized
      mode of growth of the multinucleated hyphal tip cells, whereas membrane traffic
      is adapted to the large intracellular distances. Recent work illustrates the
      usefulness of this fungus for morphological and biochemical studies on endosome
      and Golgi maturation, and on the role of microtubule-dependent motors in the long
      distance movement of endosomes. The fungus is ideally suited for genetic studies
      on the secretory pathway, as mutations impairing secretion reduce apical
      extension rates, resulting in phenotypes detectable by visual inspection of
      colonies.

PMID- 22645707
TI  - The role of non-canonical SNAREs in synaptic vesicle recycling.
AB  - An increasing number of studies suggest that distinct pools of synaptic vesicles
      drive specific forms of neurotransmission. Interspersed with these functional
      studies are analyses of the synaptic vesicle proteome which have consistently
      detected the presence of so-called "non-canonical" SNAREs that typically function
      in fusion and trafficking of other subcellular structures within the neuron. The
      recent identification of certain non-canonical vesicular SNAREs driving
      spontaneous (e.g., VAMP7 and vti1a) or evoked asynchronous (e.g., VAMP4) release
      integrates and corroborates existing data from functional and proteomic studies
      and implies that at least some complement of non-canonical SNAREs resident on
      synaptic vesicles function in neurotransmission. Here, we discuss the specific
      roles in neurotransmission of proteins homologous to each member of the classical
      neuronal SNARE complex consisting of synaptobrevin2, syntaxin-1, and SNAP-25.

PMID- 22645709
TI  - Mapping ubiquitin modifications reveals new functions for the yeast nuclear pore
      complex.
AB  - Covalent attachment of ubiquitin to target proteins, or ubiquitylation, has
      emerged as one of the most prevalent posttranslational modifications (PTMs),
      regulating nearly every cellular pathway. The diversity of functions associated
      with this particular PTM stems from the myriad ways in which a target protein can
      be modified by ubiquitin, e.g., monoubiquitin, multi-monoubiquitin, and
      polyubiquitin linkages. In the current study, we took a systematic approach to
      analyze the ubiquitylation profiles of the yeast Saccharomyces cerevisiae nuclear
      pore complex (NPC) proteins or nucleoporins. We found the yeast NPC to be
      extensively modified by ubiquitin with highly variable ubiquitylation profiles,
      suggesting that dissection of these modifications may provide new insights into
      the regulation of NPC functions and reveal additional roles for nucleoporins
      beyond nuclear transport.

PMID- 22645708
TI  - The SMS domain of Trs23p is responsible for the in vitro appearance of the TRAPP
      I complex in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae transport protein particle (TRAPP) is a family of
      related multisubunit complexes required for endoplasmic reticulum-to-Golgi
      transport (TRAPP I), endosome-to-Golgi transport (TRAPP II) or cytosol to vacuole
      targeting (TRAPP III). To gain insight into the relationship between these
      complexes, we generated random and targeted mutations in the Trs23p core subunit.
      Remarkably, at physiological salt concentrations only two peaks (TRAPP I and a
      high molecular weight peak) are detected in wild-type cells. As the salt was
      raised, the high molecular weight peak resolved into TRAPP II and III peaks.
      Deletion of a Saccharomycotina-specific domain of Trs23p resulted in
      destabilization of TRAPP I but had no effect on TRAPP II or III. This mutation
      had no observable growth phenotype, normal levels of Ypt1p-directed guanine
      nucleotide exchange factor activity in vivo and did not display any in vivo nor
      in vitro blocks in membrane traffic. Biochemical analysis indicated that TRAPP I
      could be produced from the TRAPP II/III peak in vitro by increasing the salt
      concentration. Our data suggest that the SMS domain of Trs23p is responsible for
      the in vitro appearance of TRAPP I in S. cerevisiae. The implications of these
      findings are discussed.

PMID- 22645710
TI  - Mutual cross-talk between fibronectin integrins and the EGF receptor: Molecular
      basis and biological significance.
AB  - Extension of the plasma membrane is one of the first steps in cell migration.
      Understanding how cells "choose" between various types of membrane protrusion
      enhances our knowledge of both normal and cancer cell physiology. The EGF
      receptor is a paradigm for understanding how transmembrane receptor tyrosine
      kinases regulate intracellular signaling following ligand stimulation. Evidence
      from the past decade indicates that EGF receptors also form macromolecular
      complexes with integrin receptors leading to EGF receptor transactivation during
      cell adhesion. However, relatively little is known about how these complexes form
      and impact cell migration. Our recent work characterized a molecular complex
      between EGF receptor and beta3 integrin which recognizes RGD motifs in
      extracellular matrix proteins. Complex formation requires a dileucine motif (679
      LL) in the intracellular juxtamembrane region of the EGF receptor that also
      controls whether or not the receptor undergoes Src kinase-dependent
      phosphorylation at Tyr-845. In contrast to wild-type receptors, mutant EGF
      receptors defective for Tyr-845 phosphorylation form complexes with beta1
      integrin that also binds RGD motifs. In addition, we have discovered that EGF
      receptor antagonizes small GTPase RhoA by mediating membrane recruitment of its
      regulatory GAP p190RhoGAP. In this addendum we discuss a potential new role for
      Src-dependent EGF receptor transactivation in integrin/EGF receptor complex
      formation. We also discuss how our study fits with previous observations linking
      p190RhoGAP to RhoA-dependent cytoskeletal rearrangements involved in cell
      migration, and provide new data that the EGF receptor is compartmentalized to
      relatively immature zyxin-poor focal adhesions which are the likely site of
      p190RhoGAP signaling.

PMID- 22645711
TI  - Radiation oncology: today and tomorrow.

PMID- 22645713
TI  - Radiation Dose Escalation in Stage III Non-Small-Cell Lung Cancer.
AB  - For patients with stage III non-small-cell lung cancer with unresectable or
      inoperable tumors, definitive chemoradiotherapy is often utilized. Historically,
      local control and overall survival rates have been poor. In an effort to improve
      local control, new chemotherapeutic agents in combination with higher doses of
      radiotherapy have been investigated. Early dose escalation trials date back to
      the 1980s, and the feasibility and efficacy of dose escalation for patients with
      inoperable stage III lung cancer continue to be topics of investigation. Herein,
      we review the evolution of chemotherapy as it relates to treatment of
      unresectable stage III lung cancer, and we outline the early and the more recent
      dose escalation studies. While dose escalation appears to provide a modest
      benefit in terms of preventing local failure and improving overall survival,
      advances in diagnostic imaging and radiotherapy treatment have possibly resulted
      in selection of a more favorable patient population. These variables make
      statements regarding the benefit of dose escalation challenging.

PMID- 22645712
TI  - Molecular targets for radiation oncology in prostate cancer.
AB  - Recent selected developments of the molecular science of prostate cancer (PrCa)
      biology and radiation oncology are reviewed. We present potential targets for
      molecular integration treatment strategies with radiation therapy (RT), and
      highlight potential strategies for molecular treatment in combination with RT for
      patient care. We provide a synopsis of the information to date regarding
      molecular biology of PrCa, and potential integrated research strategy for
      improved treatment of PrCa. Many patients with early-stage disease at
      presentation can be treated effectively with androgen ablation treatment,
      surgery, or RT. However, a significant portion of men are diagnosed with advanced
      stage/high-risk disease and these patients progress despite curative therapeutic
      intervention. Unfortunately, management options for these patients are limited
      and are not always successful including treatment for hormone refractory disease.
      In this review, we focus on molecules of extracellular matrix component,
      apoptosis, androgen receptor, RUNX, and DNA methylation. Expanding our knowledge
      of the molecular biology of PrCa will permit the development of novel treatment
      strategies integrated with RT to improve patient outcome.

PMID- 22645715
TI  - Xenobiotic metabolizing gene variants and renal cell cancer: a multicenter study.
AB  - BACKGROUND: The countries of Central and Eastern Europe have among the highest
      worldwide rates of renal cell cancer (RCC). Few studies have examined whether
      genetic variation in xenobiotic metabolic pathway genes may modify risk for this
      cancer. METHODS: The Central and Eastern Europe Renal Cell Cancer study was a
      hospital-based case-control study conducted between 1998 and 2003 across seven
      centers in Central and Eastern Europe. Detailed data were collected from 874
      cases and 2053 controls on demographics, work history, and occupational exposure
      to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases,
      NAD(P)H: quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH),
      catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase
      (UGT)] were selected for the present analysis based on their putative role in
      xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios
      and 95% confidence intervals were estimated by unconditional logistic regression
      adjusted for country of residence, age, sex, smoking, alcohol intake, obesity,
      and hypertension. RESULTS: We observed an increased risk of RCC with one SNP.
      After adjustment for multiple comparisons it did not remain significant. Neither
      NAT1 nor NAT2 slow acetylation was associated with disease. CONCLUSION: We
      observed no association between this pathway and renal cell cancer.

PMID- 22645716
TI  - Stereotactic body radiation therapy for patients with heavily pretreated liver
      metastases and liver tumors.
AB  - We present our initial experience with CyberKnife stereotactic body radiation
      therapy (SBRT) in a heavily pretreated group of patients with liver metastases
      and primary liver tumors. From October 2007 to June 2009, 48 patients were
      treated at the Philadelphia CyberKnife Center for liver metastases or primary
      liver tumors. We report on 30 patients with 41 discrete lesions (1-4 tumors per
      patient) who received an ablative radiation dose (BED >= 79.2 Gy10 = 66 Gy EQD2).
      The treatment goal was to achieve a high SBRT dose to the liver tumor while
      sparing at least 700 cc of liver from radiation doses above 15 Gy. Twenty-three
      patients were treated with SBRT for metastatic cancer to the liver; the remainder
      (n = 7) were primary liver tumors. Eighty-seven percent of patients had prior
      systemic chemotherapy with a median 24 months from diagnosis to SBRT; 37% had
      prior liver directed therapy. Local control was assessed for 28 patients (39
      tumors) with 4 months or more follow-up. At a median follow-up of 22 months
      (range, 10-40 months), 14/39 (36%) tumors had documented local failure. A
      decrease in local failure was found with higher doses of SBRT (p = 0.0237); 55%
      of tumors receiving a BED <= 100 Gy10 (10/18) had local failure compared with 19%
      receiving a BED > 100 Gy10 (4/21). The 2-year actuarial rate of local control for
      tumors treated with BED > 100 Gy10 was 75% compared to 38% for those patients
      treated with BED <= 100 Gy10 (p = 0.04). At last follow-up, 22/30 patients (73%)
      had distant progression of disease. Overall, seven patients remain alive with a
      median survival of 20 months from treatment and 57 months from diagnosis. To
      date, no patient experienced persistent or severe adverse effects. Despite the
      heavy pretreatment of these patients, SBRT was well tolerated with excellent
      local control rates when adequate doses (BED > 100 Gy10) were used. Median
      survival was limited secondary to development of further metastatic disease in
      the majority of patients.

PMID- 22645714
TI  - Immunotherapy targets in pediatric cancer.
AB  - Immunotherapy for cancer has shown increasing success and there is ample evidence
      to expect that progress gleaned in immune targeting of adult cancers can be
      translated to pediatric oncology. This manuscript reviews principles that guide
      selection of targets for immunotherapy of cancer, emphasizing the similarities
      and distinctions between oncogene-inhibition targets and immune targets. It
      follows with a detailed review of molecules expressed by pediatric tumors that
      are already under study as immune targets or are good candidates for future
      studies of immune targeting. Distinctions are made between cell surface antigens
      that can be targeted in an MHC independent manner using antibodies, antibody
      derivatives, or chimeric antigen receptors versus intracellular antigens which
      must be targeted with MHC restricted T cell therapies. Among the most advanced
      immune targets for childhood cancer are CD19 and CD22 on hematologic
      malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of
      synovial sarcomas, but several other molecules reviewed here also have properties
      which suggest that they too could serve as effective targets for immunotherapy of
      childhood cancer.

PMID- 22645717
TI  - Radiotherapy and erlotinib combined: review of the preclinical and clinical
      evidence.
AB  - Epidermal growth factor receptor (EGFR) is often overexpressed in tumors and has
      been associated with poor prognosis in some cancer types. The introduction of
      inhibitors of EGFR, such as erlotinib, represents an important recent advance in
      the targeted treatment of cancer. Several studies have evaluated inhibitors of
      EGFR in combination with radiotherapy, and a strong biologic rationale exists for
      the use of this combination in certain cancer types, including head and neck
      squamous cell carcinoma, non-small cell lung cancer, glioblastoma, esophageal
      cancer, and pancreatic cancer. Preclinical and clinical studies are underway to
      evaluate the combination of erlotinib with radiotherapy. To date, the results
      suggest that this approach is at least feasible and may result in modest
      improvement in outcomes compared with either modality alone.

PMID- 22645718
TI  - Fiducial-free CyberKnife stereotactic body radiation therapy (SBRT) for single
      vertebral body metastases: acceptable local control and normal tissue tolerance
      with 5 fraction approach.
AB  - This retrospective analysis examines the local control and toxicity of five
      fraction fiducial-free CyberKnife stereotactic body radiation therapy (SBRT) for
      single vertebral body (VB) metastases. All patients had favorable performance
      status (ECOG 0-1), oligometastatic disease, and no prior spine irradiation. A
      prescribed dose of 30-35 Gy was delivered in five fractions to the planning
      target volume (PTV) using the CyberKnife with X-sight spine tracking. Suggested
      maximum spinal cord and esophagus point doses were 30 and 40 Gy, respectively. A
      median 30 Gy (IQR, 30-35 Gy) dose was delivered to a median prescription isodose
      line of 70% (IQR, 65-77%) to 20 patients. At 34 months median follow-up (IQR, 25
      40 months) for surviving patients, the 1- and 2-year Kaplan-Meier local control
      estimates were 80 and 73%, respectively. Two of the five local failures were
      infield in patients who had received irradiation to the gross tumor volume and
      three were paravertebral failures just outside the PTV in patients with prior
      corpectomy. No local failures occurred in patients who completed VB radiation
      alone. The 1- and 2-year Kaplan-Meier overall survival estimates were 80 and 57%,
      respectively. Most deaths were attributed to metastatic disease; one death was
      attributed to local recurrence. The mean maximum point doses were 26.4 Gy (SD,
      5.1 Gy) to the spinal cord and 29.1 Gy (SD, 8.9 Gy) to the esophagus. Patients
      receiving maximum esophagus point doses greater than 35 Gy experienced acute
      dysphagia (Grade I/II). No spinal cord toxicity was documented. Five-fraction
      fiducial-free CyberKnife SBRT is an acceptable treatment option for newly
      diagnosed VB metastases with promising local control rates and minimal toxicity
      despite the close proximity of such tumors to the spinal cord and esophagus. A
      prospective study aimed at further enhancing local control by targeting the
      intact VB and escalating the total dose is planned.

PMID- 22645719
TI  - Confocal Laser Endomicroscopy for Diagnosis of Barrett's Esophagus.
AB  - Barrett's esophagus (BE) is established as a premalignant condition in the distal
      esophagus. Current surveillance guidelines recommend random biopsies every 1-2 cm
      at intervals of 3-5 years. Advanced endoscopic imaging of BE underwent several
      technical revolutions within the last decade including broad-field (red-flag)
      techniques (e.g., chromoendoscopy) and small-field techniques with confocal laser
      endomicroscopy (CLE) at the forefront. In this review we will focus on advanced
      endoscopic imaging using CLE for the diagnosis and characterization of BE and
      associated neoplasia. In addition, we will critically discuss the technique of
      CLE and provide some tricks and hints for the daily routine practice of CLE for
      diagnosis of BE.

PMID- 22645720
TI  - Aflibercept for the treatment of neovascular age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) can have devastating effects on vision,
      especially in its neovascular form. In the last decade, the use of intravitreal
      pharmacotherapy targeted to vascular endothelial growth factor (VEGF) has
      significantly improved the visual outcomes in patients with neovascular AMD.
      Although we have become accustomed to these unprecedented improvement outcomes,
      maintaining good visual results with anti-VEGF therapy requires tremendous
      effort, time and cost, typically involving monthly clinic visits and intravitreal
      injections. The introduction of aflibercept, an anti-VEGF drug that targets all
      isoforms of VEGF as well as placenta growth factor, has shown promise throughout
      recent clinical trials as an equally effective treatment for neovascular AMD that
      requires less frequent dosing than either ranibizumab or bevacizumab. Based on
      clinical trial results, the U.S. Food and Drug Administration approved
      aflibercept in November 2011 for use in neovascular AMD, giving patients the hope
      of alleviating some of the burden associated with treatment.

PMID- 22645721
TI  - Tafamidis for transthyretin amyloidosis.
AB  - Tafamidis meglumine (Vyndaqel(r), Pfizer) is a novel, first-in-class drug for the
      treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP), a rare
      neurodegenerative disorder characterized by progressive sensory, motor and
      autonomic impairment that is ultimately fatal. Pathogenic mutations in the
      transthyretin (TTR) protein lead to destabilization of its tetrameric structure
      and subsequent formation of amyloid aggregates. Tafamidis is a small-molecule
      inhibitor that binds selectively to TTR in human plasma and kinetically
      stabilizes the tetrameric structure of both wild-type TTR and a number of
      different mutants. Clinical trials indicate that tafamidis slows disease
      progression in patients with TTR-FAP and reduces the burden of disease,
      demonstrating improvement in small and large nerve fiber function, modified body
      mass index and lower extremity neurological examination. Tafamidis has been
      granted marketing authorization by the European Commission for the treatment of
      TTR-FAP and the U.S. Food and Drug Administration is currently reviewing this
      drug for the same indication.

PMID- 22645722
TI  - Inhaled antibiotics for lower respiratory tract infections: focus on
      ciprofloxacin.
AB  - The administration of antibiotics by the inhaled route offers an appealing and
      logical approach to treating infectious respiratory conditions. Studies in the
      cystic fibrosis (CF) population have established the efficacy of this therapeutic
      concept and inhaled antibiotic therapy is now one of the pillars of management in
      CF. There are now a number of new inhaled antibiotic formulations that have shown
      impressive preliminary evidence for efficacy in CF and are commencing phase III
      efficacy studies. Translation of this paradigm into the non-CF bronchiectasis
      population has proven difficult thus far, apparently due to problems with
      tolerability of inhaled formulations. Inhaled versions of ciprofloxacin have
      shown good tolerability and microbiological efficacy in preliminary studies,
      suggesting that effective inhaled antibiotics are finally on the horizon for this
      previously neglected patient population. The increased use of long-term inhaled
      antibiotics for a wider range of non-CF indications presents risks to the broader
      community of greater antimicrobial resistance development that must be carefully
      weighed against any demonstrated benefits.

PMID- 22645723
TI  - Current status of beta-blockers for the treatment of hypertension: an update.
AB  - beta-Adrenoceptor blockers (beta-blockers) are one of the oldest classes of
      cardiovascular drugs still in use. Several short- and long-term clinical outcomes
      studies have demonstrated their effectiveness and safety for the treatment of
      hypertension, coronary artery disease, myocardial infarction, heart failure and
      sudden cardiac death. Due to their safety and efficacy, beta-blockers have been
      recommended by several national and international committees as first-line
      therapy of hypertension. However, despite their proven benefits, their use as
      first-line treatment for hypertension has come under criticism lately. Because of
      these recent developments, several authors have recommended that beta-blockers no
      longer be used as first-line therapy for hypertension. In this review, evidence
      based information will be presented, which will demonstrate that beta-blockers
      are an effective and safe class of antihypertensive and cardiovascular drugs for
      most patients with the exception of black and elderly hypertensive patients in
      whom the beta-blockers are less effective compared to other classes of drugs. In
      addition, evidence will be presented from several major meta-analyses that beta
      blockers are equally effective in reducing blood pressure and cardiovascular
      complications. This review will also discuss differences in the mechanism of
      action of older and newer (third-generation) beta-blockers and provide evidence
      that newer agents should be preferred over the older ones in the treatment of
      hypertensive patients with certain comorbidities.

PMID- 22645724
TI  - A report from the American Academy of Dermatology 70th Annual Meeting (March 16
      20, 2012--San Diego, California, USA).
AB  - Hydrating the skin to maintain its healthy appearance and prevent diseases is a
      basic concern of all dermatologists, although all the rain persistently falling
      over San Diego during this year's American Academy of Dermatology (AAD) meeting
      seemed to point towards prevention of moisture-associated diseases rather than a
      need for skin hydration. Nevertheless, the rooms were gray inside the convention
      center, wherein scientific presentations and technical exhibits fought to attract
      the over 10,000 attendees to the meeting crowding rooms, aisles and floors. The
      following report briefly reviews news reported on therapies for skin diseases,
      focused mostly on new clinical research and the results of randomized, controlled
      trials.

PMID- 22645725
TI  - Do pragmatic esthetics make sense?

PMID- 22645726
TI  - Esthetic management of mucogingival defects after total excision in a case of
      pyogenic granuloma.
AB  - PURPOSE: Pyogenic granuloma is a relatively rare hyperplastic lesion of the oral
      tissues. Clinically it is heterogeneous and can be similar to malignant
      epithelial and mesenchymal neoplasms. The treatment of choice is the surgical
      excision of the lesion. This approach often results in unpleasant gingival
      defects, especially when the pyogenic granuloma is located in the esthetic zone.
      MATERIALS AND METHODS: This report describes the clinical and histological
      findings of pyogenic granuloma diagnosed in the maxilla of a 24-year-old female,
      as well as the successful treatment of the mucogingival defect that occurred
      following excision of the lesion, by placement of a subepithelial free connective
      tissue graft with the envelope-technique concurrently with the biopsy procedure.
      RESULTS: One-year postoperative complete root coverage of tooth 11 was achieved
      with a harmonious gingival contour, and no further recurrence was noted.
      CONCLUSION: Early diagnosis of pyogenic granuloma, and consequent therapy with
      adequate excision in a safe distance of at least 1 mm, is essential for
      prevention of neighboring structures and minimizing the risk of a relapse.
      Histopathological evaluation is obligatory to confirm the tentative clinical
      diagnosis and to exclude malignant neoplasms. The immediate esthetic
      rehabilitation with free connective tissue grafts presents a complementary
      procedure in the treatment of mucogingival defects after total excision of
      oralmucosal diseases.

PMID- 22645727
TI  - Root coverage with a modified lateral sliding flap - a case series.
AB  - The necessity of surgical root coverage is often encountered in daily clinical
      practice, mainly because of esthetic reasons. Despite the variety of available
      surgical techniques, delicate clinical scenarios may require refined surgical
      therapy approaches. The presented double sliding flap technique is designed to
      meet the special requirements encountered in the often-fragile incisal mandibular
      area. This surgical approach combines two laterally repositioned flaps with the
      dissection of the frenulum, to cover two deep neighboring recessions in the area
      of the central incisors. Providing that correct indication and adequate surgical
      tissue handling are used, this complex and advanced technique may have the
      potential to achieve complete longterm root coverage and an esthetically
      satisfying treatment outcome.

PMID- 22645728
TI  - Re-establishing esthetics of fluorosis-stained teeth using enamel microabrasion
      and dental bleaching techniques.
AB  - Dental fluorosis manifests itself as white stains on the enamel of teeth exposed
      to excessive doses of fluoride during their formation. Fluorosis usually occurs
      as a result of the ingestion of dentifrices, gels and fluoridated solutions. It
      may be diagnosed as mild, moderate or severe, and in some cases, it may cause the
      loss of the surface structure of dental enamel. The aim of this study was to
      report the clinical case of a female patient of 18 years with moderate fluorosis,
      whose smile was reestablished by the use of an enamel microabrasion technique,
      followed by in-office bleaching. A microabrasion technique with 6% hydrochloric
      acid associated with silica carbide showed to be a safe and efficient method for
      removing white fluorosis stains, while dental bleaching was useful for obtaining
      a uniform tooth shade. The association of these techniques presented excellent
      results and the patient was satisfied. Both techniques are painless, fast and
      easy to perform, in addition to preserving the dental structure. Treatment showed
      immediate and permanent results; this technique must be divulged among
      professionals and their patients.

PMID- 22645729
TI  - Survival of ceramic veneers made of different materials after a minimum follow-up
      period of five years: a systematic review and meta-analysis.
AB  - PURPOSE: The purpose of this systematic review was to compare the survival and
      complication rates of ceramic veneers produced with different techniques and
      materials after a minimum follow-up time of 5 years. MATERIALS AND METHODS: A
      literature search was conducted, using electronic databases, relevant references,
      citations and journal researching, for clinical studies reporting on the survival
      of ceramic veneers fabricated with different techniques and materials with a mean
      followup time of at least 5 years. The search period spanned from January 1980 up
      to October 2010. Event rates were calculated for the following complications
      associated with ceramic veneers: fracture, debonding, marginal discoloration,
      marginal integrity, and caries. Summary estimates, and 5-year event rates were
      reported. Comparison between subgroups of different materials, as well as
      statistical significance, was calculated using a mixed effects model. RESULTS:
      Nine studies were selected for final analysis over an initial yield of 409
      titles. No study directly compared the incidence of complications between ceramic
      veneers fabricated from different materials. Four of the included studies
      reported on the survival of ceramic veneers made out of feldspathic ceramics;
      four studies were on glass-ceramic veneers and one study included veneers
      fabricated from both materials. The mean observation time ranged between 5 and 10
      years. Overall, the 5-year complication rates were low, with the exception of
      studies reporting on extended ceramic veneers. The most frequent complication
      reported was marginal discoloration (9% at 5 years), followed by marginal
      integrity (3.9-7.7% at 5 years). There was no statistically significant
      difference in the event rates between the subgroups of different materials
      (feldspathic vs. glass-ceramic). CONCLUSION: The results of this systematic
      review showed that ceramic veneers fabricated from feldspathic or glass-ceramics
      have an adequate clinical survival for at least 5 years of clinical service, with
      very low complication rates.

PMID- 22645730
TI  - Immediate bonding to bleached enamel treated with 10% sodium ascorbate gel: a
      case report with one-year follow-up.
AB  - It is generally not recommended that bonded restoration treatment should be
      carried out immediately after bleaching treatment. However, the use of
      antioxidants such as sodium ascorbate can be useful to avoid a waiting period.
      This article is a brief review about in vitro proposals to overcome low bond
      strength values to bleached dental surfaces. It shows a one-year follow-up case
      report of a young female presenting agenesis of maxillary lateral incisors
      reshaped with direct resin composite immediately after dental bleaching. Teeth
      were bleached with a combination of in-office and at-home whitening protocols,
      followed by the application of a 10% sodium ascorbate gel for one hour, to allow
      the immediate reshaping with direct resin composite restoration. After one year,
      the clinical performance of the restoration was successful. The use of sodium
      ascorbate gel can help the clinician to perform bonding procedures immediately
      after bleaching treatments.

PMID- 22645731
TI  - Early bond strength to low-pressure sandblasted zirconia: evaluation of a self
      adhesive cement.
AB  - The debonding of a densely sintered zirconia prosthesis is a clinically reported,
      and undesirable event. A standardized, affordable adhesive cementation protocol
      for zirconia-based restorations is not yet available. The aim of this
      investigation was to assess the influence of several surface treatments on the
      initial shear bond strength of self-adhesive resin cement to densely sintered
      zirconia ceramic. Thirty densely sintered zirconia cylinders were divided into
      three groups (n = 10). Each of them received a different surface treatment:
      control (No_T), with the zirconia surface unconditioned; low pressure air
      abrasion (Sand_S) (50 um, 1 bar); and standardized air abrasion (Sand_H) (50 um,
      2.8 bar). Three more surface-treated only specimens were addressed to scanning
      electron microscope (SEM) for qualitative observations. After specimen
      fabrication, self-adhesive cementceramic interface was analyzed using SBS (shear
      bond strength) test. Mean shear bond strengths (MPa) obtained for Sand_H and
      Sand_S were 16.24 +/- 2.95 and 16.01 +/- 2.68, respectively; no statistically
      significant difference (P = 0.8580) was found between sandblasted groups. Low
      pressure air abrasion positively affected the initial self-adhesive cement
      adhesion to zirconia with respect to the No_T control group; however it did not
      prevent scratches and the formation of microcracks on the ceramic surfaces.

PMID- 22645732
TI  - Evaluation of ultrasound and light sources as bleaching catalysts - an in vitro
      study.
AB  - PURPOSE: To evaluate the efficacy of tooth bleaching with high concentration
      agents, varying the catalyst sources and exposure times. MATERIALS AND METHODS:
      Stained human third molar fragments were randomized and placed into 8 groups (n =
      5). G1: Whiteness HP Maxx (FGM, Joinville, SC, Brazil) 35% (HP)/5 min on enamel
      surface without external catalyst source; G2: HP/15 min without external catalyst
      association; G3: HP/5 min with Quartz Tungstein Halogen (QTH: Optilux 501C,
      Demetron/Kerr, Danbury, CT, USA) as a catalyst; G4: HP/15 min with QTH as a
      catalyst; G5: HP/5 min with LED/laser as a catalyst; G6: HP/15 min with LED/
      laser as a catalyst; G7: HP/5 min with ultrasound as a catalyst; G8: HP/15 min
      with ultrasound as a catalyst. The efficacy of bleaching was measured using a
      spectrophotometer (initial fotoreflectance analysis, after artificial staining
      with black tea, and after each of the bleaching sessions). Three bleaching
      sessions were performed. Data were submitted to Analysis of Variance and Tukey
      Kramer tests (P < 0.05). RESULTS: No significant differences were found between
      the catalyst sources as related to the factor of exposure time and within each
      evaluation time. For the 15 min exposure, the best result was achieved in the
      second bleaching session, except for the LED/laser group. For the 5 min exposure,
      the best result was achieved in the third session, except for ultrasound. The 15
      min of exposure time showed higher reflectance than 5 min for LED/laser and
      ultrasound in all bleaching sessions and for halogen in the second bleaching
      session. CONCLUSION: Light sources did not increase the catalytic efficiency of
      bleaching, and allowing a longer time for gel exposure on the enamel achieves
      faster results.

PMID- 22645733
TI  - Proceedings of the 2011 Autumn Meeting of the EAED (Active Members' Meeting) -
      Versailles, October 20-22nd, 2011.

PMID- 22645734
TI  - A highly sensitive sensor for Cu2+ with unmodified gold nanoparticles and DNAzyme
      by using the dynamic light scattering technique.
AB  - Copper ion (Cu(2+)) plays an important role in many biological reactions, and a
      suitable level of Cu(2+) is necessary for the regular metabolism of life. Thus
      developing a sensitive and simple method for determination of Cu(2+) is
      essential. Here, a novel and sensitive Cu(2+) sensor was developed based on
      detecting the average hydrodynamic diameter of AuNPs by using dynamic light
      scattering (DLS). Cu(2+)-specific DNAzyme was double-strand and could not adsorb
      on the surface of AuNPs, accordingly AuNPs aggregation would occur with the
      addition of NaCl. However, Cu(2+) could cleave DNAzyme and release single
      stranded DNA (ssDNA) fragments, which could adsorb on the surface of AuNPs and
      prevent them from aggregation. Such differences in DNA adsorption ability on
      AuNPs before and after the addition of Cu(2+) affected the disperse state of
      AuNPs directly, and then affected their average hydrodynamic diameter, which
      could be detected with the DLS technique. Based upon the above mentioned
      principle, detection of Cu(2+) could be realized over the range from 100 pM to
      2.0 nM, with a linear regression equation of D = 306.73 - 89.66C (C: nM, R =
      0.9953) and a detection limit of 60 pM (3delta/slope). Moreover, satisfactory
      results were obtained when the assay was applied in the detection of Cu(2+) in
      water samples.

PMID- 22645735
TI  - Chiral recognition of 2-alkyl alcohols with porphyrin J-nanoaggregates at the
      liquid-liquid interface.
AB  - The J-aggregate of diprotonated tetraphenylporphyrin (H(4)TPP(2+)) formed at the
      dodecane-water interface showed circular dichroism spectra corresponding to the
      chirality of 2-alkyl alcohols, longer than 2-butanol, added to the dodecane
      phase. The phenomenon suggested the preferential interaction between the nano
      sized J-aggregates and the chiral alcohols at the interface, and provided a
      potential use of the J-nanoaggregate as a chiral recognition probe.

PMID- 22645736
TI  - A fluorescent turn-on probe for bisulfite based on hydrogen bond-inhibited C=N
      isomerization mechanism.
AB  - A fluorescence turn-on probe for bisulfite has been developed by taking advantage
      of the specific reaction of bisulfite and aldehyde in combination with the
      hydrogen bond inhibited C=N isomerization mechanism. The practical value of this
      selective and sensitive fluorescent probe was confirmed by its application to
      detection of bisulfite in granulated sugar.

PMID- 22645738
TI  - An unusual cause of unilateral urinary tract obstruction.

PMID- 22645737
TI  - Using a nanopore for single molecule detection and single cell transfection.
AB  - We assert that it is possible to trap and identify proteins, and even
      (conceivably) manipulate proteins secreted from a single cell (i.e. the
      secretome) through transfection via electroporation by exploiting the exquisite
      control over the electrostatic potential available in a nanopore. These
      capabilities may be leveraged for single cell analysis and transfection with
      single molecule resolution, ultimately enabling a careful scrutiny of tissue
      heterogeneity.

PMID- 22645739
TI  - Turkey wins plaudits for tobacco control.

PMID- 22645740
TI  - Undercover medicine: treating Syria's wounded.

PMID- 22645741
TI  - Profile: Children of the 90s comes of age.

PMID- 22645742
TI  - The theriac in antiquity.

PMID- 22645743
TI  - Naegleria fowleri meningoencephalitis.

PMID- 22645744
TI  - Syringe access programs.

PMID- 22645745
TI  - Syringe prescription for injection drug users to prevent disease.

PMID- 22645746
TI  - [Minimal invasive, endoscopic technique of electrode placement in a cochlear
      implant].

PMID- 22645747
TI  - VEGF is clearly an exciting point of attack in the treatment of neovascular
      diseases of the retina and choroid.

PMID- 22645748
TI  - [Recent advance in carbohydrate-based cancer vaccines].
AB  - The abnormal glycans expressing on the surface of tumor cells are good targets to
      develop carbohydrate-based anti-cancer vaccines. However, one of the major
      problems is that carbohydrate antigens possess weak immunogenicity. This review
      summarizes the recent efforts to overcome this problem: glycoconjugates produced
      by coupling the carbohydrate antigens and proper carrier proteins improve their
      immunogenicity, many glycoconjugates have entered clinical trials; the vaccines
      become chemically well-defined when coupling the carbohydrate antigens with a T
      cell peptide epitope and an immunostimulant to form fully synthetic multi
      component glycoconjugate vaccines; the modification of carbohydrate antigens in
      combination with the technology of metabolic oligosaccharide engineering of tumor
      cells induces a strong immune response; and the fact that the antibodies elicited
      against the unnatural carbohydrate antigens can recognize the native carbohydrate
      antigens on tumor cells provides a new promising strategy for the development of
      anti-cancer vaccines.

PMID- 22645750
TI  - [Chemical approaches for trapping protein thiols and their oxidative
      modification].
AB  - Redox signal transduction, especially the oxidative modification of proein
      thiols, correlates with many diseases and becomes an expanding research area.
      However, there was rare method for quick and specific detection of protein thiols
      and their oxidative modification in living cells. In this article, we review the
      current chemical strategies for the detection and quantification of protein
      thiols and related cysteine oxidation. We also look into the future of the
      development of fluorescent probes for protein thiols and their potential
      application in the research of reactive cysteine proteomes and early detection of
      redox-related diseases.

PMID- 22645749
TI  - [Progress in the study of some important natural bioactive cyclopeptides].
AB  - Natural cyclopeptides are hot spots in chemical and pharmaceutical fields because
      of the wide spreading bio-resources, complex molecular structures and various
      bioactivities. Bio-producers of cyclopeptides distribute over almost every
      kingdom from bacteria to plants and animals. Many cyclopeptides contain non-coded
      amino acids and non-pepditic bonds. Most exciting characteristic of cyclopeptides
      is a range of interesting bioactivities such as antibiotics gramicidin-S (2),
      vancomycin (3) and daptomycin (4), immunosuppressive cyclosporin-A (1) and astin
      C (8), and anti-tumor aplidine (5), RA-V (6) and RA-VII (7). Compounds 1-4 are
      being used in clinics; compounds 5-8 are in the stages of clinical trial or as a
      candidate for drug research. In this review, the progress in chemical and
      bioactive studies on these important natural bioactive cyclopeptides 1-8 are
      introduced, mainly including discovery, bioactivity, mechanism, QSAR and
      synthesis.

PMID- 22645751
TI  - [Research progress of graphene-based materials in the application to
      biomedicine].
AB  - Graphene is a kind of atomic crystal with two-dimensional polycyclic aromatic
      hydrocarbons planes, which is of great concern in various fields. This paper
      reviews the latest development of graphene-based materials in biomedical research
      fields in the recent years, including in vitro and in vivo toxicity, drug
      loading, targeting controlled release, as well as photodynamic therapy. These
      researches validate that the graphene-based materials indicate promising
      prospects in the application to biomedicine.

PMID- 22645752
TI  - [The application of small molecule bioactive probes in the identification of
      cellular targets].
AB  - Identification of the cellular targets of bioactive compounds is a major
      challenge and a key issue in chemical biology and drug discovery. As an important
      technology in functional proteomics, small molecule probes play a pivotal role in
      the identification of cellular targets of bioactive compounds. This review is
      intended to introduce the application principles and structural design philosophy
      of chemical probes for the purpose of mechanistic study. Recent cases of
      successful application were also discussed to further demonstrate the principles
      and significance ofbioactive small molecule-based probes.

PMID- 22645753
TI  - [Activity of cyclic diguanylate (c-di-GMP) in bacteria and the study of its
      derivatives].
AB  - Cyclic diguanylate (c-di-GMP) is a ubiquitous second messenger present in a wide
      variety of bacteria, which is responsible for cell differentiation, biofilm
      formation, pathogenic factor generation, and so on. The level of c-di-GMP in
      bacteria is regulated by two opposing active domains, diguanylate cyclase (DGC)
      and phosphodiesterase (PDE), which are present in the same bifunctional protein,
      and in charge of the synthesis and the degradation of c-di-GMP, respectively. The
      target of c-di-GMP in the bacterial cell consists of PilZ domain and GEMM
      riboswitch, the only riboswitch that involved in signal transduction. This
      article gives an overview of c-di-GMP, focusing on its metabolic pathway,
      regulatory mechanism, biological function of c-di-GMP, and the synthesis of c-di
      GMP analogues and their biological activity.

PMID- 22645754
TI  - [Design of acetylcholinesterase inhibitor for Alzheimer's disease therapy: from
      multi-binding site inhibitors to multi-target directed ligands].
AB  - Alzheimer's disease (AD) is a complex neurodegenerative disorder which seriously
      causes the dementia in elderly people and afflicts millions of people worldwide.
      Drug discovery for Alzheimer's disease therapy has been a hot research area and a
      big challenge, in which development of acetylcholinesterase (AChE) inhibitors
      design was the most active and some AChE inhibitors are commercially available
      for AD medication already. However, practical using of commercial AChE inhibitors
      showed their limited usefulness and related adverse effects. Thus, it is
      extremely urgent to find novel AChE inhibitors with higher potency and less
      adverse effects. Based on the accurate crystallographic studies about AChE,
      strategies for multi-binding site AChE inhibitors have been formed, followed by
      design of the multi-target directed ligands. In this review, the structures and
      binding modes of commercial AChE inhibitors were briefly discussed, together with
      the development of AChE inhibitor design for AD therapy: from multi-binding site
      inhibitors to multi-target directed ligands.

PMID- 22645755
TI  - [Current applications of high-throughput DNA sequencing technology in antibody
      drug research].
AB  - Since the publication of a high-throughput DNA sequencing technology based on PCR
      reaction was carried out in oil emulsions in 2005, high-throughput DNA sequencing
      platforms have been evolved to a robust technology in sequencing genomes and
      diverse DNA libraries. Antibody libraries with vast numbers of members currently
      serve as a foundation of discovering novel antibody drugs, and high-throughput
      DNA sequencing technology makes it possible to rapidly identify functional
      antibody variants with desired properties. Herein we present a review of current
      applications of high-throughput DNA sequencing technology in the analysis of
      antibody library diversity, sequencing of CDR3 regions, identification of potent
      antibodies based on sequence frequency, discovery of functional genes, and
      combination with various display technologies, so as to provide an alternative
      approach of discovery and development of antibody drugs.

PMID- 22645756
TI  - [Research progress of layer-by-layer self-assembly technique in drug delivery].
AB  - Now the layer-by-layer self-assembling (LbL) technique has become an attention
      getting reparative methodology for ultrathin film formation. Many scientists in
      different academic areas including bioengieering, medical science, drug
      controlled release, optoelectronics dive into this technology. Among of them,
      carriers with structures which can be flexibly controlled are more useful since
      functional structure units can be assembled in layer-by-layer fashion, which is
      simplicity, chemical mildness, concealment, can achieve targeted drug delivery
      and so on. In this review, we have discussed the advantage, development,
      influential factors and applications of LbL. We have focused on reviewing the
      applications and perspective of nanoparticles, microgels and capsules were both
      fabricated via the LbL assembling at drug delivery.

PMID- 22645757
TI  - [Advances in the study of synergistic effect of anti-biofilm agents].
AB  - Biofilms are communities of surface-associated bacteria or fungi embedded in a
      self-produced extracellular polymeric matrix that are notoriously difficult to be
      eradicated and are sources of many recalcitrant infections. Treatment for biofilm
      infection with any individual drug is always less effective, while the
      combinations of different types of drugs are superior to monotherapy concerning
      the removing of biofilms. This paper focus on research progress in recent years
      for synergistic effect of drugs in combination against biofilms formed by
      Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis,
      Escherichia coli and Candida albicans.

PMID- 22645758
TI  - [Research progress of the relationship between microglia and cerebral ischemia].
AB  - Microglia are the principal immune effectors in brain and participate in a series
      ofneurodegenerative diseases. The microglial shapes are highly plastic. The
      morphology is closely related with their activation status and biological
      functions. Cerebral ischemia could induce microglial activation, and microglial
      activation is subjected to precise regulation. Microglia could play either
      protective or neurotoxic roles in cerebral ischemia. Therefore, regulating the
      expression of receptors or protein molecules on microglia, inhibiting the
      excessive activation of microglia and production of pro-inflammatory factors,
      promoting the release of neuroprotective substances might be beneficial to the
      treatment of cerebral ischemia. The study about relationship between microglia
      and cerebral ischemia will shed a light on the treatment of cerebral ischemia.
      This paper is a review of microglial activation and regulation during cerebral
      ischemia as well as related therapeutic methods.

PMID- 22645759
TI  - Multi-substituted N-phenyl-2, 2-dichloroacetamide analogues as anti-cancer drugs:
      design, synthesis and biological evaluation.
AB  - Our earlier research has shown that mono-substituted N-phenyl-2, 2
      dichloroacetamide exhibited much higher anti-cancer activity than the lead
      compound sodium dichloroacetate (DCA). In this paper, a variety of multi
      substituted N-phenyl-2, 2-dichloroacetamides were synthesized and biologically
      evaluated. The results showed that 3, 5-disubstituted N-phenyl-2, 2
      dichloroacetamide analogues had satisfactory potency. Among them, N-(3, 5
      diiodophenyl)-2, 2-dichloroacetamide had an IC50 of 2.84 micromol x L(-1) against
      non-small cell lung cancer cell line A549 and could induce cancer cell apoptosis.

PMID- 22645760
TI  - Sesquiterpenes and an intermediate 1alpha, 6beta, 11-eudesmanetriol in the
      biosynthesis of geosmin from Streptomyces sp.
AB  - One new sesquiterpene was isolated from the fermentation broth of Streptomyces
      sp. and the structure was elucidated by spectral analysis as caryolane-1, 6beta
      diol (1). An intermediate 1alpha, 6beta, 11-eudesmanetriol (2) in the
      biosynthesis of geosmin was also found in this strain which proved sequence for
      the reactions, especially bicyclization preceding dealkylation.

PMID- 22645761
TI  - [Design, synthesis and evaluation of malonic acid-based PTP1B inhibitors].
AB  - Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of
      diabetes and obesity. Phosphotyrosine (pTyr) is the substrate for PTP1B
      dephosphorylation. Malonic acid moiety was used herein as a mimic of the
      phosphate group in pTyr, and novel malonic acid derivatives 1-7 were designed,
      synthesized and evaluated as PTP1B inhibitors. Results from enzymatic assays
      indicated that compounds 3 and 4 exhibited potent inhibition against human
      recombinant PTP1B with IC50 values of 7.66 and 1.88 micromol x L(-1),
      respectively.

PMID- 22645762
TI  - [ESI fragmentation studies of six unusual nucleotide sugars].
AB  - Unusual dTDP-sugars are key intermediate in many pathogenic bacteria. In this
      study, negative-ion electrospray tandem mass spectrometry (ESI-MS-MS) with
      collision-induced dissociation (CID) was used to study the fragmentation
      characteristics of six unusual nucleotide diphosphate sugars. The results
      indicated the major fragment of the six unusual nucleoside sugars observed in the
      ESI-MS-MS spectra resulted from cleavage of diphosphate moiety and their
      characteristic fragment ions at m/z 401, 383, and 321, correspond to [TDP-H]
      together with fragment ions resulting from the loss of water and phosphate
      moiety, respectively. Furthermore, 4-position substituted change of unusual sugar
      rings affected the stability of two important characteristic fragment ions of
      [glycosyl-1"-PO3](-) and [glycosyl-1"-P2O6](-).

PMID- 22645763
TI  - [Synthesis of diethylenetriamine polydentate ligands and their DNA-cleaving
      activity].
AB  - A series of multinuclear diethylenetriamine ligands were synthesized and used as
      artificial nuclease enzyme model. Target compounds were characterized by 1H NMR,
      13C NMR, IR and ESI-MS. Preliminary studies on the cleavage of pUC19 DNA in the
      presence of metal complexes have also been performed and the results revealed
      that these complexes could act as powerful catalysts for the cleavage of pUC19
      DNA after 48 h under physiological conditions. The hydrolytic cleavage mechanism
      of DNA plasmid by title compound was confirmed by T4 DNA ligase experiment.

PMID- 22645764
TI  - [Binding mechanism of traditional Chinese medicine active component 5
      hydroxymethyl-furfural and HSA or BSA].
AB  - A combination of spectral experiment and molecular modeling techniques has been
      used to characterize the binding mechanism between an active component 5
      hydroxymethyl-furfural (5-HMF) of traditional Chinese medicine and human serum
      albumin (HSA) or bovine serum albumin (BSA). The interaction mechanism of 5-HMF
      binding with HSA/BSA is analyzed. Although the drug can bind with HSA/BSA to form
      stable complexes, there are some differences in the bond strength. The values of
      binding distances (r) are different and low, which indicated the occurrence of
      energy transfer. The drug had conformational effect on HSA/BSA, which resulted in
      different changes of hydrophobic environment of the binding domain in HSA/BSA.
      The 'phase diagram' of fluorescence revealed that the changes on the
      conformational pattern of proteins have been affected by drug conformed to the
      "all-or-none" pattern. The interactions between drug and protein influenced by
      Co(II) were also discussed. Its effects acting on 5-HMF-HSA/BSA interactions are
      different. The computational modeling method was used to study the interaction
      between 5-HMF and HSA/BSA. The results of molecular model studies revealed that
      the binding modes for drug-serum albumin systems are mainly hydrophobic
      interactions and hydrogen bonding. These results are in accordance with spectral
      results. The research results have given a better theoretical reference for the
      study of pharmacological mechanism of 5-hydroxymethyl-furfural.

PMID- 22645766
TI  - [Cu2+ and Zn2+-induced aggregation of amyloid-beta peptide].
AB  - To study the effect of Cu2+ and Zn2+ on amyloid-beta peptides (Abeta)
      aggregation, the morphology, size and cell toxicity of Abeta40 aggregates formed
      with the metal ions have been observed by the methods including ultraviolet
      spectroscopy, fluorescence spectroscopy and transmission electron microscopy. The
      results showed that Cu2+ and Zn2+ can accelerate Abeta40 aggregation, and both
      changed the morphology and size of Abeta40 aggregates. Zn2+ induced Abeta40 to
      form fibrous Abeta40 aggregates, while the amorphous and fibrous aggregates were
      produced by the interaction between Cu2+ and Abeta40. In addition, H2O2 was
      produced when Abeta40 reduced Cu2+. The relationship between metal ions and
      Abeta40 aggregates was analyzed, and the function of metal ions in Alzheimer's
      disease (AD) was illustrated in the research.

PMID- 22645765
TI  - [Preparation and characterization of mono PEGylated recombinant human interferon
      omega].
AB  - The amino group PEGylation of rhIFNomega with monomethoxy polyethylene glycol
      succinimidyl succinate (mPEG-SS, 20 000) was investigated, and the modified
      mixture was separated and purified by ion exchange chromatography and gel
      filtration chromatography. Under the optimized purification conditions, the
      average content ofmono PEG-rhIFNomega in the collect liquid reached 182 microg x
      mL(-1). The average purified yield of mono PEG-rhIFNomega exceed to 22%, and the
      purity of mono PEG-rhIFNomega was greater than 98% by SDS-PAGE and RP-HPLC.
      Relative molecular mass of mono PEG-rhIFNomega was 43 790 detected by MALDI-TOF
      MS. The apparent molecular mass measured by SDS-PAGE was about 60 810. The
      purified PEG-rhIFNomega has the characteristics of typical PEGylated protein.
      Activity reservation rate of mono PEG-rhIFNomega was 15.0%, while the
      antigenicity decreased by at least 64 folds. In addition, the acid stability,
      thermal stability and stability in serum and trypsin solution of mono PEG
      rhIFNomega were markedly better than those of the rhIFNomega. The pharmacological
      properties of mono PEG-rhIFNomega were significantly improved. The prepared PEG
      rhIFNomega might be developed to a novel safe and long-acting interferon.

PMID- 22645767
TI  - [NNIspm, a polyamine derivative, induces cellular senescence of human hepatoma
      HepG2 cells and its molecular mechanism].
AB  - This study is to examine the effects of NNIspm-mediated cellular senescence of
      HepG2 cells and elucidate its potential molecular mechanism. Cellular senescence
      was detected with senescence-associated beta-galactosidase staining. Cell cycle
      distribution, intracellular fluorescence intensity and accumulation of
      intracellular reactive oxygen species (ROS) were detected by high content
      screening (HCS). Protein expression was detected by Western blotting. Polyamines
      content was analyzed by high performance liquid chromatography (HPLC). The
      results demonstrated that NNIspm significantly induced HepG2 cells senescence.
      This effect was due to the decrease of intracellular polyamines, the arrest at
      G0/G1 phase and an increase of ROS level. The molecular senescence marker p21
      increased significantly after NNIspm treatment. In contrast, the protein
      expressions of Cyclin E and CDK2 were obvious down-regulation. The results
      indicated that cellular senescence induced by NNIspm was one of its antitumor
      mechanisms.

PMID- 22645768
TI  - [Differential proteins in esophageal squamous cell line EC9706/CDDP identified by
      SILAC quantitative proteomic approach].
AB  - Multidrug resistance (MDR) is one of the main causes leading to the failure in
      cancer treatment. Differential proteins between esophageal squamous cell
      carcinoma (ESCC) cell line EC9706 and its cisdiamminedichloroplatinum (CDDP)
      resistant subline EC9706/CDDP revealed by quantitative analysis may provide
      deeper insights into the molecular mechanisms of MDR implicated in ESCC.
      EC9706/CDDP was generated by exposure of its parental sensitive EC9706 to a step
      wise increase of CDDP concentration during EC9706 cultivation. The stable isotope
      labeling with amino acids in cell culture (SILAC) was used to label EC9706 and
      EC9706/CDDP with heavy and light medium, separately. Mixed peptides derived from
      EC9706 and EC9706/CDDP were analyzed by high performance liquid chromatography
      electrospray ionization-mass spectrometry (HPLC-ESI-MS/MS) and subsequently
      subjected to bioinformatics analysis to identify differential proteins between
      EC9706 and EC9706/CDDP. Compared to parental EC9706, EC9706/CDDP manifested
      phenotypes of slow proliferation, cell pleomorphology, atypia and increased
      resistant-index 3.23. Seventy-four differential proteins identified in the
      present study belongs to various families with multiple functions, such as
      cytoskeleton (20%), energy metabolism (11%), transcription regulation and DNA
      repair (11%), redox homeostasis (9.5%), protein biosynthesis and mRNA processing
      (12%), ribosome constituent (8.1%), molecular chaperone (8.1%),
      immunity/inflammation (5.4%), intracellular transport (5.4%) and nucleosome
      assembly (2.7%), which indicated that development of MDR is a complicated process
      involving dysregulation of multiple molecules and pathways. The data is of great
      value for in-depth elucidation of molecular mechanisms of the MDR implicated in
      ESCC and may represent potential molecular targets for future therapeutic
      development.

PMID- 22645770
TI  - [Nursing scientist could advance to first lady].

PMID- 22645769
TI  - [Setting the tempo].

PMID- 22645771
TI  - Bone mineral density testing: how often? A new study suggests that many older
      women don't need frequent testing.

PMID- 22645773
TI  - Prevention.  Researchers call for better education on condom use.

PMID- 22645772
TI  - Treating pelvic organ prolapse.  Options range from doing nothing to surgical
      repair.

PMID- 22645774
TI  - Research.  HIV in injection drug users down, but fewer are tested for virus.

PMID- 22645775
TI  - Policy.  New guidelines to optimize entry, retention in HIV/AIDS care.

PMID- 22645776
TI  - Offer HIV tests to patients with certain disease, cancers.

PMID- 22645778
TI  - Grants.  Planned Parenthood granted injunction in grant dispute.

PMID- 22645777
TI  - SSI.  ALJ properly considered vocational testimony before denial.

PMID- 22645779
TI  - Criminal.  Conviction of man who failed to reveal HIV status affirmed.

PMID- 22645780
TI  - Insurance.  Allegations that man used imposter for policy 'speculative'.

PMID- 22645781
TI  - [15th world congress of psychiatry].

PMID- 22645782
TI  - [In Process Citation].

PMID- 22645783
TI  - [In Process Citation].

PMID- 22645785
TI  - [In Process Citation].

PMID- 22645784
TI  - [In Process Citation].

PMID- 22645786
TI  - Orientation of horizontal cell axon terminals in the streak of the turtle retina.

PMID- 22645787
TI  - Myenteric ganglia from the adult guinea-pig small-intestine in tissue-culture.
AB  - Myenteric ganglia dissociated from the small intestine of adult guinea-pigs
      survived in long-term culture (1-2 months) and progressed to structural
      organization resembling the myenteric plexus in situ. Developmental changes were
      similar to cultures derived from neonatal intestine. After one week, the neurons
      gathered into clusters on a glial cell carpet. Processes from the neurons
      branched and ramified over the glial substrate. As the cultures matured, the
      processes joined into tracts and the neurons and glia formed compact aggregates
      reminiscent of ganglia interconnected by fibre bundles. Injection of dye revealed
      characteristic Dogiel I and II neuronal morphology. Electrical recording
      identified electrical and synaptic behaviour comparable to intact myenteric
      plexus, longitudinal muscle preparations, except slow synaptic excitation was
      absent. Pharmacological responses to forskolin and 5-hydroxytryptamine were
      essentially the same as in freshly dissected preparations. Lucifer yellow
      injected into single glial cells spread to a broad population indicative of the
      dye coupling found among glia in the myenteric plexus in situ. The results
      suggest that adult myenteric ganglia in culture are a useful model for
      investigation of aspects of enteric neurobiology including: (a) formation of
      connections in microcircuits; (b) cellular neurophysiology of enteric neurons;
      (c) neuropharmacology; and (4) cell biology of neuronal-glial interactions in the
      myenteric plexus.

PMID- 22645788
TI  - Pathology consultation on vitamin D testing: clinical indications for 25(OH)
      vitamin D measurement.

PMID- 22645789
TI  - An audit of shade reproduction of fixed metal ceramic prostheses.
AB  - This investigation aimed to evaluate the colour difference between metal ceramic
      restorations and their corresponding shades and any reasons for a colour mismatch
      in the dental laboratory. The colour of 50 consecutive metal ceramic restorations
      produced in a laboratory was measured using a spectrophotometer and compared to
      the shade tabs. Colour reproduction was optimal at porcelain thicknesses between
      1.4-1.6 mm, varied between technicians within the same laboratory and was better
      for shades in the 2M group. Most crowns were above the threshold for a clinically
      acceptable shade match and almost all crowns were lighter than the corresponding
      shade tab.

PMID- 22645790
TI  - An evidence based approach for the provision of resin-bonded bridgework.
AB  - Resin bonded bridgework (RBB) is a technique often overlooked by practitioners
      despite a large amount of evidence supporting the technique. In Cork University
      Dental School an evidence-based, standardised approach for the delivery of RBB by
      undergraduate students has been developed over the past 10 years. The aim of this
      study was to evaluate the success of this standardised approach on the delivery
      of RBB by students. 222 bridges were reviewed which had been delivered over a 6
      year time period between 2002 and 2007. A success rate of 84.1% was achieved with
      a mean survival time of 41 months. This study illustrates that predictable and
      highly successful RBB can be delivered by inexperienced clinicians using an
      evidence-based, standardised approach.

PMID- 22645791
TI  - The influence of storage on dimensional changes in maxillary acrylic denture
      bases and the effect on tooth displacement.
AB  - This study investigated the influence of both room temperature storage and water
      storage on tooth displacement in complete dentures. Thirty maxillary dentures
      were manufactured and processed using 3 different curing cycles; long, short
      conventional and microwaved. Distances between fixed points on teeth were
      measured and the dentures stored at room temperature for 24 weeks. After storage,
      the distances were measured again and the dentures then stored in water at 37
      degrees C for 24 weeks, when the distances were re-evaluated. Anteroposterior
      distances demonstrated contraction in all acrylic resins. Incisor-incisor (air = 
      8.5% and water = -7.0%) and molar-molar (room = -1.8% and water = -1.1%) distance
      changes were greater in the Onda-Cryl resin (p < 0.05), whereas the premolar
      premolar (room = -2.2% and water = -1.7%) distance was higher in the QC-20 resin
      (p < 0.05).

PMID- 22645792
TI  - In vitro failure of crowns produced by two CAD/CAM systems.
AB  - Previous laboratory studies have demonstrated satisfactory fracture resistance of
      all-ceramic crowns placed using a resin-composite luting material and a dentine
      bonding system. This study investigated the fracture resistance of teeth restored
      using CAD/CAM technology, namely, Zirconia Based crowns and Cerec produced
      feldspathic porcelain crowns, both luted with a self adhesive resin luting
      material (RelyX Unicem Clicker 3M ESPE). Standardized preparations were carried
      out on two groups often sound, unrestored, maxillary premolar teeth. Ceramic
      crowns were constructed to have a thickness of 2mm at their midline fissure.
      Compressive fracture resistance was determined for each group using a Universal
      Testing Machine. The failure modes were also examined visually and interpreted
      according to a chosen scale. Mean Compressive fracture resistance of 746 (147)N
      and 1630 (175)N were recorded for the Cerec and Lava groups respectively;
      differences were statistically significant (p < 0.001). The fracture resistance
      of teeth restored with Lava crowns is significantly greater than a similar group
      of teeth restored with Cerec crowns.

PMID- 22645793
TI  - Splinting effect on posterior implants under various loading modes: a 3D finite
      element analysis.
AB  - This three-dimensional finite element study compared stresses, intensities and
      displacements of three mandibular posterior implants restored with cemented
      crowns (two molars and a premolar in straight line), splinted versus non
      splinted. Hundred newton occlusal loads were vertically or horizontally applied,
      either on one single crown or on all of them. Maximal stresses and implants
      displacements were higher under horizontal loading. Splinting major effects
      appeared under single horizontal load with a decrease in stresses (34-49%) and
      displacements (16-19%) of the loaded crown. Splinting seems more appropriate for
      implant-supported restorations submitted to frequent single horizontal or oblique
      loads than vertical ones.

PMID- 22645794
TI  - The effect on cast post dimensions of casting investment and airborne particle
      abrasion.
AB  - Cast posts can sometimes prove difficult to seat fully during fitting. This study
      compared two different liquid/water dilutions for phosphate bonded investment and
      the effect of controlled airborne particle abrasion on resulting post diameter.
      After measuring polymeric post patterns (n = 18), 3 groups were invested using
      concentrated solution and 3 groups using dilute solution. After casting they were
      weighed and remeasured then exposed to airborne particle abrasion. Both solutions
      produced oversized cast posts. Mean diameter reduction during airborne particle
      abrasion was 8 microm/10s taking an average of 41s to reach precast size. Where a
      post pattern fits tightly, airborne particle abrasion for 70s should reduce the
      casting sufficiently to accommodate the cement lute.

PMID- 22645795
TI  - Immediate replacement complete dentures: pitfalls of ignoring traditional
      teaching and established practice.
AB  - A thirty-year-old female had immediate replacement dentures made by a general
      practitioner and her teeth extracted and the dentures fitted under general
      anaesthetic by her local oral surgeon three months previously. Anterior and
      posterior teeth had been extracted and no attempt had been made to smooth or
      shape the ridges. Both dentures were constructed with gum fitted anterior teeth
      without labial flanges. This treatment differs from traditional immediate
      replacement complete denture teaching. Traditionally, when possible the posterior
      teeth would have been extracted first and then once there had been a period of
      healing the immediate replacement complete dentures would have been made
      replacing the remaining anterior teeth. A trans-septal alveolotomy would have
      been performed, which would reduce the labial undercut on the edentulous ridge so
      that the denture could have a labial flange which would enable a border seal to
      be established to enhance retention but would not displace the lip. Care would
      have been taken to ensure that the fit surface of the denture would reflect the
      change in ridge shape that would follow healing. The divergence of this treatment
      management from a traditional approach raises important questions. In the past
      oral surgeons were well versed in pre-prosthetic surgery. As demand for this type
      of treatment has declined, so has the opportunity for oral surgery trainees, who
      themselves may have limited experience in prosthetic dentistry, to learn the
      techniques involved. Teaching of this form of removable prosthetic dentistry has
      been reduced reflecting the reduced frequency of this presenting condition.

PMID- 22645796
TI  - Acrylic strengthened casts for removable partial denture for occlusion
      equilibration.
AB  - A removable partial denture (RPD) remount cast must resist wear or breakage,
      present a rigid surface, and ensure a solid support for an accurate equilibration
      of the occlusion for a RPD. This article describes a procedure of processing a
      thin layer of tooth colored acrylic resin over the dental plaster to present wear
      and fracture-resistant incisal/occlusal surfaces without involving a third
      material.

PMID- 22645797
TI  - Effect of two different disinfectants on dimensional stability of newer alginate
      impression materials over five days.
AB  - The effect of two different disinfectants on the dimensional stability of two
      alginate impression materials over five days was investigated. 60 impressions
      were made under standardised conditions, 30 with each alginate, of which ten were
      disinfected in each disinfectant and ten were controls. Impressions were stored
      over a period of five days in a container with 100% humidity. Measurements were
      made between four points. Two-way analysis of variance indicated no differences
      in the change from baseline to day 5 between any of the combinations of alginate
      and disinfectant. Only two of the changes between baseline and day 5 reached
      statistical significance at the p < 0.01 level. Therefore it can be concluded
      that within the limitations of this study when newer alginate impression
      materials are disinfected they remain stable over 5 days.

PMID- 22645798
TI  - Prosthetic rehabilitation of an individual papillary unit: a clinical report.
AB  - This article is a clinical and technical report to illustrate the prosthetic
      correction of an individual interdental papilla, which had been lost due to
      periodontal disease. The patient presented with localised aggressive
      periodontitis and was successfully treated non-surgically. As a result of the
      periodontal disease and its management, the interdental papilla between the 11
      and 21 were lost and prosthetically replaced. The clinical details of the case
      and the technical procedures are fully illustrated within this article.

PMID- 22645799
TI  - Evaluation of sorption, solubility and staining of universal and silorane resin
      based composites.
AB  - Resin-based composite staining is a multifactoral phenomenon and can be caused by
      intrinsic and extrinsic factors. The purpose of this study was to compare
      staining, sorption and solubility of silorane resin-based and universal resin
      based composites. Five different resin-based composites (4 Seasons, Charisma,
      Filtek Silorane, Filtek Supreme and Grandio) were tested. Twenty five specimens
      were prepared (10 mm diameter and 1.5 mm thick). To staining test, the specimens
      were divided into 3 groups (n = 5): distilled water (control), coffee and red
      wine. The specimens were immersed in one of the solutions at 37 degrees C for 7
      days. Using the values of L*, a*, b*, color variation (CIEDE2000) was determined.
      For sorption and solubility test, the specimens were divided into 2 groups (n =
      5): with previous desiccation (Group 1) and with no previous desiccation (Group
      2). The methodology used for sorption and solubility test was based on ISO
      4049:2000. The results presented no significant difference in staining between
      composites. In sorption and solubility test, Filtek Silorane presented the
      smallest values, followed by Grandio. Under tested experimental conditions, it is
      not possible to assert the dependence of staining in sorption that composites are
      undergone. There was no significant correlation between colour change and
      sorption values.

PMID- 22645801
TI  - Dynamic functional impression technique for severely resorbed alveolar ridges.
AB  - The process of bone resorption can reduce the volume of the alveolar crest, which
      makes may make difficult impression taking of the alveolar tissue and the
      subsequent fit of a new denture. This clinical report describes a fast and simple
      technique for impressions of edentulous ridges to replace complete dentures,
      using a temporary tissue conditioner material on the denture base. The existing
      denture must cover the whole supporting area and should be in harmony with the
      adjacent oral structures. This technique reduces the number of steps involved and
      minimizes treatment time and expenses.

PMID- 22645800
TI  - Fragment reattachment associated with pulpotomy in a posterior tooth with
      incomplete root formation.
AB  - This article reports a case of preserving pulp vitality combined with aesthetics
      and functional reconstruction of an immature permanent molar extensively
      destroyed because of a carious lesion. After a pulpotomy using calcium hydroxide,
      the tooth crown was restored by bonding a dental fragment obtained from an
      extracted tooth from another individual. Aspects of diagnosis and treatment that
      directly affect the prognosis of the techniques are discussed. Radiographic and
      clinical follow-up for two years showed complete root development and a very
      satisfactory restoration with regard to aesthetics and function.

PMID- 22645802
TI  - Dimensional stability of elastomeric impression materials: a critical review of
      the literature.
AB  - The aim of the present paper was to review the literature concerning the
      dimensional stability of dental elastomeric impression materials, to support
      recommendations to control the variables that influence the accuracy of these
      materials. An electronic search of the Scopus and PubMed databases was performed
      in November 2010. Articles were selected according to the following inclusion
      criteria: investigation of the dimensional stability of dental elastomers, an
      experimental study, sample size reported, laboratory tests described, and
      published in an English language peer-reviewed journal. The search resulted in 47
      articles published between 1958 and 2008; of these, 24 were selected for
      inclusion in the present study. Great variability was discovered in the
      experimental methodologies used, such as different working times, temperatures
      and storage mediums for the impressions, impression techniques, material
      thicknesses, tray types, and methods of evaluation. Despite the lack of
      standardization among the studies, this review supports the following
      recommendations to control the dimensional stability: impressions should be
      stored at temperatures between 21 +/- 2 degrees C; polyether impressions should
      be stored in an environment with a relative humidity below 50%; time until
      pouring has been settled for each elastomer material.

PMID- 22645803
TI  - Performance assessment of Vita Easy Shade spectrophotometer on colour measurement
      of aesthetic dental materials.
AB  - Four different shades were used to produce 20 samples of resin-based composite
      and 20 samples of porcelain to evaluate the performance ability of an intra oral
      test spectrophotometer compared to a reference spectrophotometer. The absolute
      colour coordinates CIELAB values measured with both spectrophotometers were
      significantly different (p < 0.001). However, a high correlation was found (p <
      0.001) despite the low concordance noticed. The colour difference deltaE* values
      calculated between different shades also were significantly different between
      both spectrophotometers (p < 0.05). Therefore, the Easy Shade can be used in
      dental practice and dental research with some limitations.

PMID- 22645804
TI  - Modified technique of resection denture prosthesis fabrication for a patient with
      segmental mandibulectomy--a case report.
AB  - The rehabilitation of patients following maxillary & mandibular resection is
      challenging. A prosthesis supported with dental implants is often the treatment
      of choice, but implants cannot be used predictably in all clinical situations. A
      tissue supported post resection denture is usually the most acceptable treatment
      option left in these situations. This case report describes management of a
      patient who had undergone segmental mandibulectomy & subsequently rehabilitated
      with resection denture prosthesis. Conventional treatment planning was modified
      at various stages of fabrication to improve the quality of the final prosthesis.

PMID- 22645805
TI  - Use of mineral trioxide aggregate (MTA by postgraduates in restorative dentistry
      in the UK.
AB  - All postgraduate trainees in Restorative Dentistry within the United Kingdom were
      contacted by e-mail and invited toparticipate in a structured on-line
      questionnaire regarding MTA usage. Responses were received from 46/65 (70.8%)
      postgraduate trainees. MTA was used by 15/46 (32.6%) trainees in the primary
      dentition and 46/46 (100%) in the permanent dentition. Barriers to the use of MTA
      in the permanent dentition related to material cost and in the primary dentition,
      the lack of an evidence base. Overall, 32/46 (69.6%) had received tuition during
      their postgraduate programme and 21/46 (45.7%) indicated an interest in further
      educational opportunities in material use.

PMID- 22645806
TI  - Pressure pain threshold of mucosa after tooth extraction under removable denture
      bases.
AB  - This study explored the pressure pain threshold (PPT) of the mucosa after tooth
      extraction. The PPTs of the wounded mucosa of eight volunteer subjects were
      observed at 7, 30, and 90 days after tooth extraction. The PPTs at 30 days and 90
      days were approximately two and three times higher respectively, than those at 7
      days. As time passed, the values for the PPTs after tooth extraction increased in
      all regions. At 90 days after tooth extraction, the PPTs are about 97% recovered
      compared to the PPTs of the contralateral points.

PMID- 22645807
TI  - Identification of distinct movement patterns in Pacific leatherback turtle
      populations influenced by ocean conditions.
AB  - Interactions with fisheries are believed to be a major cause of mortality for
      adult leatherback turtles (Dermochelys coriacea), which is of particular concern
      in the Pacific Ocean, where they have been rapidly declining. In order to
      identify where these interactions are occurring and how they may be reduced, it
      is essential first to understand the movements and behavior of leatherback
      turtles. There are two regional nesting populations in the East Pacific (EP) and
      West Pacific (WP), comprising multiple nesting sites. We synthesized tracking
      data from the two populations and compared their movement patterns. A switching
      state-space model was applied to 135 Argos satellite tracks to account for
      observation error, and to distinguish between migratory and area-restricted
      search behaviors. The tracking data, from the largest leatherback data set ever
      assembled, indicated that there was a high degree of spatial segregation between
      EP and WP leatherbacks. Area-restricted search behavior mainly occurred in the
      southeast Pacific for the EP leatherbacks, whereas the WP leatherbacks had
      several different search areas in the California Current, central North Pacific,
      South China Sea, off eastern Indonesia, and off southeastern Australia. We also
      extracted remotely sensed oceanographic data and applied a generalized linear
      mixed model to determine if leatherbacks exhibited different behavior in relation
      to environmental variables. For the WP population, the probability of area
      restricted search behavior was positively correlated with chlorophyll-a
      concentration. This response was less strong in the EP population, but these
      turtles had a higher probability of search behavior where there was greater Ekman
      upwelling, which may increase the transport of nutrients and consequently prey
      availability. These divergent responses to oceanographic conditions have
      implications for leatherback vulnerability to fisheries interactions and to the
      effects of climate change. The occurrence of leatherback turtles within both
      coastal and pelagic areas means they have a high risk of exposure to many
      different fisheries, which may be very distant from their nesting sites. The EP
      leatherbacks have more limited foraging grounds than the WP leatherbacks, which
      could make them more susceptible to any temperature or prey changes that occur in
      response to climate change.

PMID- 22645808
TI  - The Scotia Sea krill fishery and its possible impacts on dependent predators:
      modeling localized depletion of prey.
AB  - The nature and impact of fishing on predators that share a fished resource is an
      important consideration in ecosystem-based fisheries management. Krill (Euphausia
      superba) is a keystone species in the Antarctic, serving as a fundamental forage
      source for predators and simultaneously being subject to fishing. We developed a
      spatial multispecies operating model (SMOM) of krill-predator fishery dynamics to
      help advise on allocation of the total krill catch among 15 small-scale
      management units (SSMUs) in the Scotia Sea, with a goal to reduce the potential
      impact of fishing on krill predators. The operating model describes the
      underlying population dynamics and is used in simulations to compare different
      management options for adjusting fishing activities (e.g., a different spatial
      distribution of catches). The numerous uncertainties regarding the choice of
      parameter values pose a major impediment to constructing reliable ecosystem
      models. The pragmatic solution proposed here involves the use of operating models
      that are composed of alternative combinations of parameters that essentially try
      to bound the uncertainty in, for example, the choice of survival rate estimates
      as well as the functional relationships between predators and prey. Despite the
      large uncertainties, it is possible to discriminate the ecosystem impacts of
      different spatial fishing allocations. The spatial structure of the model is
      fundamental to addressing concerns of localized depletion of prey in the vicinity
      of land-based predator breeding colonies. Results of the model have been
      considered in recent management deliberations for spatial allocations of krill
      catches in the Scotia Sea and their associated impacts on dependent predator
      species.

PMID- 22645809
TI  - What are we protecting? Fisher behavior and the unintended consequences of
      spatial closures as a fishery management tool.
AB  - Spatial closures like marine protected areas (MPAs) are prominent tools for
      ecosystem-based management in fisheries. However, the adaptive behavior of
      fishermen, the apex predator in the ecosystem, to MPAs may upset the balance of
      fishing impacts across species. While ecosystem-based management (EBM) emphasizes
      the protection of all species in the environment, the weakest stock often
      dominates management attention. We use data before and after the implementation
      of large spatial closures in a North Pacific trawl fishery to show how closures
      designed for red king crab protection spurred dramatic increases in Pacific
      halibut bycatch due to both direct displacement effects and indirect effects from
      adaptations in fishermen's targeting behavior. We identify aspects of the
      ecological and economic context of the fishery that contributed to these
      surprising behaviors, noting that many multispecies fisheries are likely to share
      these features. Our results highlight the need either to anticipate the
      behavioral adaptations of fishermen across multiple species in reserve design, a
      form of implementation error, or to design management systems that are robust to
      these adaptations. Failure to do so may yield patterns of fishing effort and
      mortality that undermine the broader objectives of multispecies management and
      potentially alter ecosystems in profound ways.

PMID- 22645810
TI  - Effects of sex change on the implications of marine reserves for fisheries.
AB  - Marine reserves have become widely used in biodiversity conservation and are
      increasingly proposed as fisheries management tools. Previous modeling studies
      have found that reserves may increase or decrease yields, depending on local
      environmental conditions and on the specific life-history traits of the fishery
      species. Sex-changing (female-to-male) fish are targets of some of the most
      important commercial and recreational fisheries in the world. The potential for
      disproportionate removal of the larger, older sex of such species requires new
      theory to facilitate our understanding of how reserves will affect the yields of
      surrounding fisheries, relative to fishes with separate sexes. We investigated
      this question by modeling the effects of marine reserves on a non-sex-changing
      and a sex-changing population. We used demographic parameter estimates for the
      common coral trout as a baseline, and we conducted extensive sensitivity analyses
      to determine how sustainable yields of sex-changing species are likely to be
      affected by reserves across a broad range of life-history parameters. Our
      findings indicate that fisheries for sex-changing species are unlikely to receive
      the same yield-enhancing benefit that non-sex-changing fisheries enjoy from
      marine reserves, and that often reserves tend to reduce sustainable yields for a
      given overall population size. Specifically, the increased egg production and
      high fertilization success within reserves is more than offset by the reduced egg
      production and fertilization success in the fished areas, relative to a system in
      which fishing mortality is distributed more evenly over the entire system. A key
      reason for this appears to be that fertilization success is reduced, on average,
      when males are unevenly distributed among subpopulations, as is the case when
      reserves are present. These findings suggests that, for sex-changing populations,
      reserves are more suited to rebuilding overfished populations and sustaining
      fishery viability, rather than enhancing fishery yields. These results are robust
      over a range of sex-change regimes, stock-recruitment relationships, adult
      mortality rates, individual growth strategies, and fertilization-success
      functions. Our findings highlight the importance of considering the different
      contributions of males and females to population growth and fishery yields when
      evaluating the efficacy of marine reserves for enhancement of fished species.

PMID- 22645811
TI  - Multi-scale marine biodiversity patterns inferred efficiently from habitat image
      processing.
AB  - Cost-effective proxies of biodiversity and species abundance, applicable across a
      range of spatial scales, are needed for setting conservation priorities and
      planning action. We outline a rapid, efficient, and low-cost measure of spectral
      signal from digital habitat images that, being an effective proxy for habitat
      complexity, correlates with species diversity and requires little image
      processing or interpretation. We validated this method for coral reefs of the
      Great Barrier Reef (GBR), Australia, across a range of spatial scales (1 m to 10
      km), using digital photographs of benthic communities at the transect scale and
      high-resolution Landsat satellite images at the reef scale. We calculated an
      index of image-derived spatial heterogeneity, the mean information gain (MIG),
      for each scale and related it to univariate (species richness and total abundance
      summed across species) and multivariate (species abundance matrix) measures of
      fish community structure, using two techniques that account for the hierarchical
      structure of the data: hierarchical (mixed-effect) linear models and distance
      based partial redundancy analysis. Over the length and breadth of the GBR, MIG
      alone explained up to 29% of deviance in fish species richness, 33% in total fish
      abundance, and 25% in fish community structure at multiple scales, thus
      demonstrating the possibility of easily and rapidly exploiting spatial
      information contained in digital images to complement existing methods for
      inferring diversity and abundance patterns among fish communities. Thus, the
      spectral signal of unprocessed remotely sensed images provides an efficient and
      low-cost way to optimize the design of surveys used in conservation planning. In
      data-sparse situations, this simple approach also offers a viable method for
      rapid assessment of potential local biodiversity, particularly where there is
      little local capacity in terms of skills or resources for mounting in-depth
      biodiversity surveys.

PMID- 22645812
TI  - Quantifying and comparing size selectivity among Alaskan sockeye salmon
      fisheries.
AB  - Quantifying long-term size-selective harvest patterns is necessary for
      understanding the potential evolutionary effects on exploited species. The
      comparison of fishery selection patterns on the same species subject to different
      gear types, in different areas, and over multi-decadal periods can reveal the
      factors influencing selection. In this study we quantified and compared size
      selective harvest by nine Alaskan sockeye salmon (Oncorhynchus nerka) fisheries
      to understand overall patterns. We calculated length-specific linear selection
      differentials (the difference in average length of fish before vs. after
      fishing), which are produced by different combinations of exploitation rates and
      length-selectivity values, and nonlinear standardized differentials, describing
      disruptive selection, across all years for each fishery. Selection differentials
      varied among years, but larger fish were caught in 73% of years for males and 84%
      of years for females, leaving smaller fish to spawn. Disruptive selection was
      observed on female and male fish in 84% and 92% of years, respectively. Linear
      selection was stronger on females than males in 77% of years examined, and
      disruptive selection was stronger on males in 71% of years. Selection pressure
      was influenced by a combination of factors under and beyond management control;
      analyses using mixed-effects models indicated that fisheries were less size
      selective in years when fish were larger than average and had lower exploitation
      rates. The observed harvest of larger than average sockeye salmon is consistent
      with the hypothesis that size-selective fishing contributes to decreasing age and
      length at maturation trends over time, but temporal variability in selection and
      strong disruptive selection suggests that the overall directional pressure is
      weaker than is often assumed in evolutionary models.

PMID- 22645813
TI  - Eradication via destratification: whole-lake mixing to selectively remove rainbow
      smelt, a cold-water invasive species.
AB  - Invasive species can have severe effects on aquatic ecosystems. After invasions
      occur, eradication should be considered whenever the potential loss of ecosystem
      services outweighs the cost of the eradication method. Here we evaluate the
      possibility of destratifying Crystal Lake, Wisconsin, USA, to eradicate the
      invasive fish rainbow smelt (Osmerus mordax). We modeled the effects of three
      destratification scenarios (non-, low-, and high-mixing) using both physical and
      biological models. Field observations were used to calibrate the models. Water
      temperatures estimated from 18 unique DYRESM simulations were used in a
      bioenergetics model to estimate growth of five age classes of rainbow smelt under
      normal and destratified conditions. Our simulations indicate that
      destratification can eliminate optimal rainbow smelt thermal habitat resulting in
      mortality. Destratified lake temperatures also surpassed several physiological
      critical temperatures. Bioenergetics simulations predicted a weight loss of 45
      55% in yearling and adult rainbow smelt. We found that destratification is
      potentially effective for eradicating cold-water species in temperate lakes.

PMID- 22645814
TI  - Invasive salmonids and lake order interact in the decline of puye grande Galaxias
      platei in western Patagonia lakes.
AB  - Salmonid fishes, native to the northern hemisphere, have become naturalized in
      many austral countries and appear linked to the decline of native fishes,
      particularly galaxiids. However, a lack of baseline information and the potential
      for confounding anthropogenic stressors have led to uncertainty regarding the
      association between salmonid invasions and galaxiid declines, especially in
      lakes, as these have been much less studied than streams. We surveyed 25 lakes in
      the Aysen region of Chilean Patagonia, including both uninvaded and salmonid
      invaded lakes. Abundance indices (AI) of Galaxias platei and salmonids (Salmo
      trutta and Oncorhynchus mykiss) were calculated using capture-per-unit-effort
      data from gillnets, minnow traps, and electrofishing. We also measured additional
      environmental variables, including deforestation, lake morphometrics, altitude,
      and hydrological position (i.e., lake order). An information-theoretic approach
      to explaining the AI of G. platei revealed that by far the strongest effect was a
      negative association with the AI of salmonids. Lake order was also important, and
      using structural equation modeling, we show that this is an indirect effect
      naturally constraining the salmonid invasion success in Patagonia. Supporting
      this conclusion, an analysis of an independent data set from 106 mountain lakes
      in western Canada showed that introduced salmonids are indeed less successful in
      low-order lakes. Reproductive failure due to insufficient spawning habitat and
      harsh environmental conditions could be the cause of these limits to salmonid
      success. The existence of this effect in Chilean Patagonia suggests that low
      order lakes are likely to provide natural ecological refugia for G. platei.
      Finally, pristine, high-order lakes should be actively protected as these have
      become rare and irreplaceable unspoiled references of the most diverse, natural
      lake ecosystems in Patagonia.

PMID- 22645815
TI  - Aquatic and terrestrial organic matter in the diet of stream consumers:
      implications for mercury bioaccumulation.
AB  - The relative contribution of aquatic vs. terrestrial organic matter to the diet
      of consumers in fluvial environments and its effects on bioaccumulation of
      contaminants such as mercury (Hg) remain poorly understood. We used stable
      isotopes of carbon and nitrogen in a gradient approach (consumer isotope ratio
      vs. periphyton isotope ratio) across temperate streams that range in their pH to
      assess consumer reliance on aquatic (periphyton) vs. terrestrial (riparian
      vegetation) organic matter, and whether Hg concentrations in fish and their prey
      were related to these energy sources. Taxa varied in their use of the two
      sources, with grazing mayflies (Heptageniidae), predatory stoneflies (Perlidae),
      one species of water strider (Metrobates hesperius), and the fish blacknose dace
      (Rhinichthys atratulus) showing strong connections to aquatic sources, while
      Aquarius remigis water striders and brook trout (Salvelinus fontinalis) showed a
      weak link to in-stream production. The aquatic food source for consumers,
      periphyton, had higher Hg concentrations in low-pH waters, and pH was a much
      better predictor of Hg in predatory invertebrates that relied mainly on this food
      source vs. those that used terrestrial C. These findings suggest that stream
      biota relying mainly on dietary inputs from the riparian zone will be partially
      insulated from the effects of water chemistry on Hg availability. This has
      implications for the development of a whole-system understanding of nutrient and
      material cycling in streams, the choice of taxa in contaminant monitoring
      studies, and in understanding the fate of Hg in stream food webs.

PMID- 22645816
TI  - Genetic structure among coastal tailed frog populations at Mount St. Helens is
      moderated by post-disturbance management.
AB  - Catastrophic disturbances often provide "natural laboratories" that allow for
      greater understanding of ecological processes and response of natural
      populations. The 1980 eruption of the Mount St. Helens volcano in Washington,
      USA, provided a unique opportunity to test biotic effects of a large-scale
      stochastic disturbance, as well as the influence of post-disturbance management.
      Despite severe alteration of nearly 600 km2 of habitat, coastal tailed frogs
      (Ascaphus truei) were found within a portion of the blast area five years after
      eruption. We investigated the genetic source of recolonization within the blast
      area and tested whether post-eruption salvage logging and subsequent tree
      planting influenced tailed frog movement patterns. Our results support widespread
      recolonization across the blast area from multiple sources, as all sites are
      grouped into one genetic cluster. Landscape genetic models suggest that gene flow
      through the unmanaged portion of the blast area is influenced only by distance
      between sites and the frost-free period (r2 = 0.74). In contrast, gene flow
      pathways within the blast area where salvage logging and replanting occurred post
      eruption are strongly limited (r2 = 0.83) by the physiologically important
      variables of heat load and precipitation. These data suggest that the lack of
      understory and coarse wood (downed and standing dead tree boles) refugia in
      salvaged areas may leave frogs more susceptible to desiccation and mortality than
      those frogs moving through the naturally regenerated area. Simulated populations
      based on the landscape genetic models show an increase in the inbreeding
      coefficient in the managed area relative to the unmanaged blast area. In sum, we
      show surprising resilience of an amphibian species to a catastrophic disturbance,
      and we suggest that, at least for this species, naturally regenerating habitat
      may better maintain long-term genetic diversity of populations than actively
      managed habitat.

PMID- 22645817
TI  - Geologic processes influence the effects of mining on aquatic ecosystems.
AB  - Geologic processes strongly influence water and sediment quality in aquatic
      ecosystems but rarely are geologic principles incorporated into routine
      biomonitoring studies. We test if elevated concentrations of metals in water and
      sediment are restricted to streams downstream of mines or areas that may
      discharge mine wastes. We surveyed 198 catchments classified as "historically
      mined" or "unmined," and based on mineral-deposit criteria, to determine whether
      water and sediment quality were influenced by naturally occurring mineralized
      rock, by historical mining, or by a combination of both. By accounting for
      different geologic sources of metals to the environment, we were able to
      distinguish aquatic ecosystems limited by metals derived from natural processes
      from those due to mining. Elevated concentrations of metals in water and sediment
      were not restricted to mined catchments; depauperate aquatic communities were
      found in unmined catchments. The type and intensity of hydrothermal alteration
      and the mineral deposit type were important determinants of water and sediment
      quality as well as the aquatic community in both mined and unmined catchments.
      This study distinguished the effects of different rock types and geologic sources
      of metals on ecosystems by incorporating basic geologic processes into reference
      and baseline site selection, resulting in a refined assessment. Our results
      indicate that biomonitoring studies should account for natural sources of metals
      in some geologic environments as contributors to the effect of mines on aquatic
      ecosystems, recognizing that in mining-impacted drainages there may have been
      high pre-mining background metal concentrations.

PMID- 22645818
TI  - Population dynamics and control of invasive Spartina alterniflora: inference and
      forecasting under uncertainty.
AB  - Managing invaded ecosystems entails making decisions about control strategies in
      the face of scientific uncertainty and ecological stochasticity. Statistical
      tools such as model selection and Bayesian decision analysis can guide decision
      making by estimating probabilities of outcomes under alternative management
      scenarios, but these tools have seldom been applied in invasion ecology. We
      illustrate the use of model selection and Bayesian methods in a case study of
      smooth cordgrass (Spartina alterniflora) invading Willapa Bay, Washington. To
      address uncertainty in model structure, we quantified the weight of evidence for
      two previously proposed hypotheses, that S. alterniflora recruitment varies with
      climatic conditions (represented by sea surface temperature) and that recruitment
      is subject to an Allee effect due to pollen limitation. By fitting models to time
      series data, we found strong support for climate effects, with higher per capita
      seedling production in warmer years, but no evidence for an Allee effect based on
      either the total area invaded or the mean distance between neighboring clones. We
      used the best-supported model to compare alternative control strategies,
      incorporating uncertainty in parameter estimates and population dynamics. For a
      fixed annual removal effort, the probability of eradication in 10 years was
      highest, and final invaded area lowest, if removals targeted the smallest clones
      rather than the largest or randomly selected clones. The relationship between
      removal effort and probability of eradication was highly nonlinear, with a sharp
      threshold separating -0% and -100% probability of success, and this threshold was
      95% lower in simulations beginning early rather than late in the invasion. This
      advantage of a rapid response strategy is due to density-dependent population
      growth, which produces alternative stable equilibria depending on the initial
      invasion size when control begins. Our approach could be applied to a wide range
      of invasive species management problems where appropriate data are available.

PMID- 22645819
TI  - Potential aboveground biomass in drought-prone forest used for rangeland
      pastoralism.
AB  - The restoration of cleared dry forest represents an important opportunity to
      sequester atmospheric carbon. In order to account for this potential, the
      influences of climate, soils, and disturbance need to be deciphered. A data set
      spanning a region defined the aboveground biomass of mulga (Acacia aneura) dry
      forest and was analyzed in relation to climate and soil variables using a
      Bayesian model averaging procedure. Mean annual rainfall had an overwhelmingly
      strong positive effect, with mean maximum temperature (negative) and soil depth
      (positive) also important. The data were collected after a recent drought, and
      the amount of recent tree mortality was weakly positively related to a measure of
      three-year rainfall deficit, and maximum temperature (positive), soil depth
      (negative), and coarse sand (negative). A grazing index represented by the
      distance of sites to watering points was not incorporated by the models. Stark
      management contrasts, including grazing exclosures, can represent a substantial
      part of the variance in the model predicting biomass, but the impact of
      management was unpredictable and was insignificant in the regional data set.
      There was no evidence of density-dependent effects on tree mortality. Climate
      change scenarios represented by the coincidence of historical extreme rainfall
      deficit with extreme temperature suggest mortality of 30.1% of aboveground
      biomass, compared to 21.6% after the recent (2003-2007) drought. Projections for
      recovery of forest using a mapping base of cleared areas revealed that the
      greatest opportunities for restoration of aboveground biomass are in the higher
      rainfall areas, where biomass accumulation will be greatest and droughts are less
      intense. These areas are probably the most productive for rangeland pastoralism,
      and the trade-off between pastoral production and carbon sequestration will be
      determined by market forces and carbon-trading rules.

PMID- 22645820
TI  - Hierarchical analysis of vegetation dynamics over 71 years: soil-rainfall
      interactions in a Chihuahuan Desert ecosystem.
AB  - Proliferation of woody plants in grasslands and savannas is a persistent problem
      globally. This widely observed shift from grass to shrub dominance in rangelands
      worldwide has been heterogeneous in space and time largely due to cross-scale
      interactions among soils, climate, and land-use history. Our objective was to use
      a hierarchical framework to evaluate the relationship between spatial patterns in
      soil properties and long-term shrub dynamics in the northern Chihuahuan Desert of
      New Mexico, USA. To meet this objective, shrub patch dynamics from 1937 to 2008
      were characterized at patch and landscape scales using historical imagery and a
      recent digital soils map. Effects of annual precipitation on patch dynamics on
      two soils revealed strong correlations between shrub growth on deep sandy soils
      and above-average rainfall years (r = 0.671, P = 0.034) and shrub colonization
      and below-average rainfall years on shallow sandy soils (r = 0.705, P = 0.023).
      Patch-level analysis of demographic patterns revealed significant differences
      between shrub patches on deep and shallow sandy soils during periods of above-
      and below-average rainfall. Both deep and shallow sandy soils exhibited low shrub
      cover in 1937 (1.0% +/- 2.3% and 0.3% +/- 1.3%, respectively [mean +/- SD]) and
      were characterized by colonization or appearance of new patches until 1960.
      However, different demographic responses to the cessation of severe drought on
      the two soils and increased frequency of wet years after 1960 have resulted in
      very different endpoints. In 2008 a shrubland occupied the deep sandy soils with
      cover at 19.8% +/- 9.1%, while a shrub-dominated grassland occurred on the
      shallow sandy soils with cover at 9.3% +/- 7.2%. Present-day shrub vegetation
      constitutes a shifting mosaic marked by the coexistence of patches at different
      stages of development. Management implications of this long-term multi-scale
      assessment of vegetation dynamics support the notion that soil properties may
      constrain grassland remediation. Such efforts on sandy soils should be focused on
      sites characterized by near-surface water-holding capacity, as those lacking
      available water-holding capacity in the shallow root zone pose challenges to
      grass recovery and survival.

PMID- 22645821
TI  - Can initial intraspecific spatial aggregation increase multi-year coexistence by
      creating temporal priority?
AB  - Both intraspecific spatial aggregation and temporal priority effects have the
      potential to increase long-term species coexistence. Theory and models suggest
      that intraspecific aggregation can facilitate coexistence via limited dispersal
      or asymmetric interaction distances. During community assembly, intraspecific
      aggregation may also delay interactions between more and less competitive
      species, thus creating opportunities for priority effects to facilitate longer
      term coexistence. Few empirical studies have tested predictions about aggregation
      and coexistence, especially in the context of community assembly or ecological
      restoration. We investigated (1) impacts of intraspecific aggregation on the
      assembly of eight-species communities over three years, (2) the scale dependence
      of these impacts, and (3) implications for California prairie restoration. We
      planted eight native species in each of 19, 5 m wide, octagonal plots. Species
      were either interspersed throughout the plot or aggregated into eight, 2.2-m(2),
      wedge-shaped, monospecific sectors. Over three years, species diversity declined
      more quickly in interspersed plots than in aggregated plots. Two species had
      higher cover or increased more in interspersed than aggregated plots and were
      identified as "aggressives." Four species had higher cover or increased more in
      aggregated than interspersed plots and were identified as "subordinates." Within
      aggregated plots, aggressive species expanded beyond the sector in which they
      were originally seeded. Cover of aggressive species increased faster and reached
      higher values in sectors that were adjacent to the originally planted sector,
      compared to nonadjacent sectors. Cover of aggressive species also increased more
      and faster near plot centers, compared to plot edges. Areas near plot centers
      were representative of smaller aggregation patches since species were planted
      closer to heterospecific neighbors. Two subordinate species maintained higher
      cover near plot edges than near plot centers. Moreover, two subordinate species
      maintained higher cover when seeded in sectors farther away from aggressive
      species. These results suggest that initial intraspecific aggregation can
      facilitate species coexistence for at least three years, and larger aggregation
      patches may be more effective than smaller ones in the face of dispersing
      dominants. The creation of temporal priority effects may represent an
      underappreciated pathway by which intraspecific aggregation can increase
      coexistence. Restorationists may be able to maintain more diverse communities by
      planting in a mosaic of monospecific patches.

PMID- 22645822
TI  - Corridors promote fire via connectivity and edge effects.
AB  - Landscape corridors, strips of habitat that connect otherwise isolated habitat
      patches, are commonly employed during management of fragmented landscapes. To
      date, most reported effects of corridors have been positive; however, there are
      long-standing concerns that corridors may have unintended consequences. Here, we
      address concerns over whether corridors promote propagation of disturbances such
      as fire. We collected data during prescribed fires in the world's largest and
      best replicated corridor experiment (Savannah River Site, South Carolina, USA),
      six -50-ha landscapes of open (shrubby/herbaceous) habitat within a pine
      plantation matrix, to test several mechanisms for how corridors might influence
      fire. Corridors altered patterns of fire temperature through a direct
      connectivity effect and an indirect edge effect. The connectivity effect was
      independent of fuel levels and was consistent with a hypothesized wind-driven
      "bellows effect." Edges, a consequence of corridor implementation, elevated leaf
      litter (fuel) input from matrix pine trees, which in turn increased fire
      temperatures. We found no evidence for corridors or edges impacting patterns of
      fire spread: plots across all landscape positions burned with similar
      probability. Impacts of edges and connectivity on fire temperature led to changes
      in vegetation: hotter-burning plots supported higher bunch grass cover during the
      field season after burning, suggesting implications for woody/herbaceous species
      coexistence. To our knowledge, this represents the first experimental evidence
      that corridors can modify landscape-scale patterns of fire intensity. Corridor
      impacts on fire should be carefully considered during landscape management, both
      in the context of how corridors connect or break distributions of fuels and the
      desired role of fire as a disturbance, which may range from a management tool to
      an agent to be suppressed. In our focal ecosystem, longleaf pine woodland,
      corridors might provide a previously unrecognized benefit during prescribed
      burning activities, by promoting fire intensity, which may assist in promoting
      plant biodiversity.

PMID- 22645823
TI  - Experimental tree removal in tallgrass prairie: variable responses of flora and
      fauna along a woody cover gradient.
AB  - Woody plant encroachment is a worldwide phenomenon in grassland and savanna
      systems whose consequence is often the development of an alternate woodland
      state. Theoretically, an alternate state may be associated with changes in system
      state variables (e.g., species composition) or abiotic parameter shifts (e.g.,
      nutrient availability). When state-variable changes are cumulative, such as in
      woody plant encroachment, the probability of parameter shifts increases as system
      feedbacks intensify over time. Using a Before-After Control-Impact (BACI) design,
      we studied eight pairs of grassland sites undergoing various levels of eastern
      redcedar (Juniperus virginiana) encroachment to determine whether responses of
      flora and fauna to experimental redcedar removal differed according to the level
      of pretreatment redcedar cover. In the first year after removal, herbaceous plant
      species diversity and evenness, woody plant evenness, and invertebrate family
      richness increased linearly with pretreatment redcedar cover, whereas increases
      in small-mammal diversity and evenness were described by logarithmic trends. In
      contrast, increases in woody plant diversity and total biomass of terrestrial
      invertebrates were accentuated at levels of higher pretreatment cover. Tree
      removal also shifted small-mammal species composition toward a more grassland
      associated assemblage. During the second year postremoval, increases in
      herbaceous plant diversity followed a polynomial trend, but increases in most
      other metrics did not vary along the pretreatment cover gradient. These changes
      were accompanied by extremely high growing-season precipitation, which may have
      homogenized floral and faunal responses to removal. Our results demonstrate that
      tree removal increases important community metrics among grassland flora and
      fauna within two years, with some responses to removal being strongly influenced
      by the stage of initial encroachment and modulated by climatic variability. Our
      results underscore the importance of decisive management for reversing the
      effects of woody plant encroachment in imperiled grassland ecosystems.

PMID- 22645824
TI  - Uncertainty in invasive alien species listing.
AB  - Lists of invasive alien species (IAS) are essential for preventing, controlling,
      and reporting on the state of biological invasions. However, these lists suffer
      from a range of errors, with serious consequences for their use in science,
      policy, and management. Here we (1) collated and classified errors in IAS listing
      using a taxonomy of uncertainty; and (2) estimated the size of these errors using
      data from a completed listing exercise, with the purpose of better understanding,
      communicating, and dealing with them. Ten errors were identified. Most result
      from a lack of knowledge or measurement error (epistemic uncertainty), although
      two were a result of context dependence and vagueness (linguistic uncertainty).
      Estimates of the size of the effects of these errors were substantial in a number
      of cases and unknown in others. Most errors, and those with the largest estimated
      effect, result in underestimates of IAS numbers. However, there are a number of
      errors where the size and direction of the effect remains poorly understood. The
      effect of differences in opinion between specialists is potentially large,
      particularly for data-poor taxa and regions, and does not have a clearly
      directional or consistent effect on the size and composition of IAS lists. Five
      tactics emerged as important for reducing uncertainty in IAS lists, and while
      uncertainty will never be removed entirely, these approaches will significantly
      improve the transparency, repeatability, and comparability of IAS lists.
      Understanding the errors and uncertainties that occur during the process of
      listing invasive species, as well as the potential size and nature of their
      effects on IAS lists, is key to improving the value of these lists for
      governments, management agencies, and conservationists. Such understanding is
      increasingly important given positive trends in biological invasion and the
      associated risks to biodiversity and biosecurity.

PMID- 22645825
TI  - Plant diversity partitioning in Mediterranean croplands: effects of farming
      intensity, field edge, and landscape context.
AB  - Farmland biodiversity is affected by factors acting at various spatial scales.
      However, most studies to date have focused on the field or farm scales that only
      account for local (alpha) diversity, and these may underestimate the contribution
      of other diversity components (beta diversity) to total (gamma) farmland
      diversity. In this work, we aimed to identify the most suitable management
      options and the scale at which they should be implemented to maximize benefits
      for diversity. We used a multi-scale additive partitioning approach, with data on
      plant diversity from 640 plots in 32 cereal crop fields from three agricultural
      regions of central Spain that differed in landscape configuration. We analyzed
      the relative contribution to overall plant diversity of different diversity
      components at various spatial scales and how these diversity components responded
      to a set of local (application of agri-environment schemes [AES] and position
      within the field) and landscape (field size and landscape connectivity and
      composition) factors. Differences in species composition among regions and then
      among fields within regions contributed most to overall plant diversity. Positive
      edge effects were found on all diversity components at both the field- and
      regional scales, whereas application of AES benefited all diversity components
      only at the field scale. Landscape factors had strong influences on plant
      diversity, especially length of seminatural boundaries, which increased species
      richness at both the field and the regional scales. In addition, positive effects
      of percentage of nonproductive land-uses in the landscape were found on all
      diversity components at the regional scale. Results showed that components that
      contributed most to overall plant diversity were not benefited by current AES. We
      conclude that agri-environmental policies should incorporate and prioritize
      measures aimed at the maintenance of seminatural boundaries and patches of
      nonproductive habitats within agricultural landscapes, through landscape
      planning, cross-compliance, or high nature-value farmland programs. These options
      will help to conserve overall plant diversity at regional scales, as well as the
      spillover of plant species from such seminatural elements into crops, especially
      in Mediterranean areas that still harbor extensive farming and relatively complex
      landscapes.

PMID- 22645826
TI  - Controlling annual weeds in cereals by deploying crop rotation at the landscape
      scale: Avena sterilis as an example.
AB  - Weed control through crop rotation has mainly been studied in a nonspatial
      context. However, weed seeds are often spread beyond the crop field by a variety
      of vectors. For weed control to be successful, weed management should thus be
      evaluated at the landscape level. In this paper we assess how seed dispersal
      affects the interactions between crop rotation and landscape heterogeneity
      schemes with regard to weed control. A spatially explicit landscape model was
      developed to study both short- and long-term weed population dynamics under
      different management scenarios. We allowed for both two- and three-crop species
      rotations and three levels of between-field weed seed dispersal. All rotation
      scenarios and seed dispersal fractions were analyzed for both completely
      homogeneous landscapes and heterogeneous landscapes in which more than one crop
      was present. The potential of implementing new weed control methods was also
      analyzed. The model results suggest that, like crop rotation at the field level,
      crop rotation implemented at the landscape level has great potential to control
      weeds, whereby both the number of crop species and the cropping sequence within
      the crop rotation have significant effects on both the short- and long-term weed
      population densities. In the absence of seed dispersal, weed populations became
      extinct when the fraction of each crop in the landscape was randomized. In
      general, weed seed densities increased in landscapes with increasing similarity
      in crop proportions, but in these landscapes the level of seed dispersal affected
      which three-crop species rotation sequence was most efficient at controlling the
      weed densities. We show that ignoring seed dispersal between fields might lead to
      the selection of suboptimal tactics and that homogeneous crop field patches that
      follow a specific crop rotation sequence might be the most sustainable method of
      weed control. Effective weed control through crop rotation thus requires
      coordination between farmers with regard to cropping sequences, crop allocation
      across the landscape, and/ or the fraction of each crop across the landscape.

PMID- 22645827
TI  - Assessing aboveground tropical forest biomass using Google Earth canopy images.
AB  - Reducing Emissions from Deforestation and Forest Degradation (REDD) in efforts to
      combat climate change requires participating countries to periodically assess
      their forest resources on a national scale. Such a process is particularly
      challenging in the tropics because of technical difficulties related to large
      aboveground forest biomass stocks, restricted availability of affordable,
      appropriate remote-sensing images, and a lack of accurate forest inventory data.
      In this paper, we apply the Fourier-based FOTO method of canopy texture analysis
      to Google Earth's very-high-resolution images of the wet evergreen forests in the
      Western Ghats of India in order to (1) assess the predictive power of the method
      on aboveground biomass of tropical forests, (2) test the merits of free Google
      Earth images relative to their native commercial IKONOS counterparts and (3)
      highlight further research needs for affordable, accurate regional aboveground
      biomass estimations. We used the FOTO method to ordinate Fourier spectra of 1436
      square canopy images (125 x 125 m) with respect to a canopy grain texture
      gradient (i.e., a combination of size distribution and spatial pattern of tree
      crowns), benchmarked against virtual canopy scenes simulated from a set of known
      forest structure parameters and a 3-D light interception model. We then used 15 1
      ha ground plots to demonstrate that both texture gradients provided by Google
      Earth and IKONOS images strongly correlated with field-observed stand structure
      parameters such as the density of large trees, total basal area, and aboveground
      biomass estimated from a regional allometric model. Our results highlight the
      great potential of the FOTO method applied to Google Earth data for biomass
      retrieval because the texture-biomass relationship is only subject to 15%
      relative error, on average, and does not show obvious saturation trends at large
      biomass values. We also provide the first reliable map of tropical forest
      aboveground biomass predicted from free Google Earth images.

PMID- 22645828
TI  - Downscaling species occupancy from coarse spatial scales.
AB  - The measurement and prediction of species' populations at different spatial
      scales is crucial to spatial ecology as well as conservation biology. An
      efficient yet challenging goal to achieve such population estimates consists of
      recording empirical species' presence and absence at a specific regional scale
      and then trying to predict occupancies at finer scales. So far the majority of
      the methods have been based on particular species' distributional features deemed
      to be crucial for downscaling occupancy. However, only a minority of them have
      dealt explicitly with specific spatial features. Here we employ a wide class of
      spatial point processes, the shot noise Cox processes (SNCP), to model species
      occupancies at different spatial scales and show that species' spatial
      aggregation is crucial for predicting population estimates at fine scales
      starting from coarser ones. These models are formulated in continuous space and
      locate points regardless of the arbitrary resolution that one employs to study
      the spatial pattern. We compare the performances of nine models, calibrated at
      regional scales and demonstrate that a very simple class of SNCP, the Thomas
      process, is able to outperform other published models in predicting occupancies
      down to areas four orders of magnitude smaller than the ones employed for the
      parameterization. We conclude by explaining the ability of the approach to infer
      spatially explicit information from spatially implicit measures, the potential of
      the framework to combine niche and spatial models, and the possibility of
      reversing the method to allow upscaling.

PMID- 22645829
TI  - Inconsistent definitions of "urban" result in different conclusions about the
      size of urban carbon and nitrogen stocks.
AB  - There is conflicting evidence about the importance of urban soils and vegetation
      in regional C budgets that is caused, in part, by inconsistent definitions of
      "urban" land use. We quantified urban ecosystem contributions to C stocks in the
      Boston (Massachusetts, USA) Metropolitan Statistical Area (MSA) using several
      alternative urban definitions. Development altered aboveground and belowground C
      and N stocks, and the sign and magnitude of these changes varied by land use and
      development intensity. Aboveground biomass (live trees, dbh > or = 5 cm) for the
      MSA was 7.2 +/- 0.4 kg C/m2 (mean +/- SE), reflecting a high proportion of forest
      cover. Vegetation C was highest in forest (11.6 +/- 0.5 kg C/m2), followed by
      residential (4.6 +/- 0.5 kg C/m2), and then other developed (2.0 +/- 0.4 kg C/m2)
      land uses. Soil C (0-10 cm depth) followed the same pattern of decreasing C
      concentration from forest, to residential, to other developed land uses (4.1 +/-
      0.1, 4.0 +/- 0.2, and 3.3 +/- 0.2 kg C/m2, respectively). Within a land use type,
      urban areas (which we defined as > 25% impervious surface area [ISA] within a 1
      km(2) moving window) generally contained less vegetation C, but slightly more
      soil C, than nonurban areas. Soil N concentrations were higher in urban areas
      than nonurban areas of the same land use type, except for residential areas,
      which had similarly high soil N concentrations. When we compared our definition
      of urban to other commonly used urban extents (U.S. Census Bureau, Global Rural
      Urban Mapping Project [GRUMP], and the MSA itself), we found that urban soil (1 m
      depth) and vegetation C stocks spanned a wide range, from 14.4 +/- 0.8 to 54.5 +/
      3.4 Tg C and from 4.2 +/- 0.4 to 27.3 +/- 3.2 Tg C, respectively. Conclusions
      about the importance of urban soils and vegetation to regional C and N stocks are
      very sensitive to the definition of urban used by the investigators. Urban areas,
      regardless of definition, are rapidly expanding in their extent; a systematic
      understanding of how our development patterns influence ecosystems is necessary
      to inform future development choices.

PMID- 22645830
TI  - Economic-based projections of future land use in the conterminous United States
      under alternative policy scenarios.
AB  - Land-use change significantly contributes to biodiversity loss, invasive species
      spread, changes in biogeochemical cycles, and the loss of ecosystem services.
      Planning for a sustainable future requires a thorough understanding of expected
      land use at the fine spatial scales relevant for modeling many ecological
      processes and at dimensions appropriate for regional or national-level policy
      making. Our goal was to construct and parameterize an econometric model of land
      use change to project future land use to the year 2051 at a fine spatial scale
      across the conterminous United States under several alternative land-use policy
      scenarios. We parameterized the econometric model of land-use change with the
      National Resource Inventory (NRI) 1992 and 1997 land-use data for 844 000 sample
      points. Land-use transitions were estimated for five land-use classes (cropland,
      pasture, range, forest, and urban). We predicted land-use change under four
      scenarios: business-as-usual, afforestation, removal of agricultural subsidies,
      and increased urban rents. Our results for the business-as-usual scenario showed
      widespread changes in land use, affecting 36% of the land area of the
      conterminous United States, with large increases in urban land (79%) and forest
      (7%), and declines in cropland (-16%) and pasture (-13%). Areas with particularly
      high rates of land-use change included the larger Chicago area, parts of the
      Pacific Northwest, and the Central Valley of California. However, while land-use
      change was substantial, differences in results among the four scenarios were
      relatively minor. The only scenario that was markedly different was the
      afforestation scenario, which resulted in an increase of forest area that was
      twice as high as the business-as-usual scenario. Land-use policies can affect
      trends, but only so much. The basic economic and demographic factors shaping land
      use changes in the United States are powerful, and even fairly dramatic policy
      changes, showed only moderate deviations from the business-as-usual scenario.
      Given the magnitude of predicted land-use change, any attempts to identify a
      sustainable future or to predict the effects of climate change will have to take
      likely land-use changes into account. Econometric models that can simulate land
      use change for broad areas with fine resolution are necessary to predict trends
      in ecosystem service provision and biodiversity persistence.

PMID- 22645831
TI  - Emerging prion disease drives host selection in a wildlife population.
AB  - Infectious diseases are increasingly recognized as an important force driving
      population dynamics, conservation biology, and natural selection in wildlife
      populations. Infectious agents have been implicated in the decline of small or
      endangered populations and may act to constrain population size, distribution,
      growth rates, or migration patterns. Further, diseases may provide selective
      pressures that shape the genetic diversity of populations or species. Thus,
      understanding disease dynamics and selective pressures from pathogens is crucial
      to understanding population processes, managing wildlife diseases, and conserving
      biological diversity. There is ample evidence that variation in the prion protein
      gene (PRNP) impacts host susceptibility to prion diseases. Still, little is known
      about how genetic differences might influence natural selection within wildlife
      populations. Here we link genetic variation with differential susceptibility of
      white-tailed deer to chronic wasting disease (CWD), with implications for fitness
      and disease-driven genetic selection. We developed a single nucleotide
      polymorphism (SNP) assay to efficiently genotype deer at the locus of interest
      (in the 96th codon of the PRNP gene). Then, using a Bayesian modeling approach,
      we found that the more susceptible genotype had over four times greater risk of
      CWD infection; and, once infected, deer with the resistant genotype survived 49%
      longer (8.25 more months). We used these epidemiological parameters in a multi
      stage population matrix model to evaluate relative fitness based on genotype
      specific population growth rates. The differences in disease infection and
      mortality rates allowed genetically resistant deer to achieve higher population
      growth and obtain a long-term fitness advantage, which translated into a
      selection coefficient of over 1% favoring the CWD-resistant genotype. This
      selective pressure suggests that the resistant allele could become dominant in
      the population within an evolutionarily short time frame. Our work provides a
      rare example of a quantifiable disease-driven selection process in a wildlife
      population, demonstrating the potential for infectious diseases to alter host
      populations. This will have direct bearing on the epidemiology, dynamics, and
      future trends in CWD transmission and spread. Understanding genotype-specific
      epidemiology will improve predictive models and inform management strategies for
      CWD-affected cervid populations.

PMID- 22645832
TI  - Safety and efficacy of bilateral topical application of rocuronium bromide for
      mydriasis in European kestrels (Falco tinnunculus).
AB  - The avian iris is mainly composed of striated muscle fibers, and the topical
      parasympatholytic drugs used in mammals to induce pupil dilation are ineffective
      in birds. The achievement of mydriasis in conscious birds is only possible by
      using neuromuscular blocking agents such as curariform drugs. To determine the
      efficacy of the neuromuscular blocking agent rocuronium bromide as a mydriatic
      agent in European kestrels (Falco tinnunculus) and to assess possible adverse
      effects due to its use, 10 kestrels received a single topical instillation with a
      pipette of 0.12 mg of rocuronium in each eye (total dose, 0.24 mg/bird). Pupil
      diameter was measured with a pupillary gauge, and pupillary light reflex was
      assessed by using a standard light source from time zero (Tbase) to 250 minutes
      after application (T250). Baseline pupil size (Tbase) was 3.30 (0.71) mm in both
      eyes. Maximal mydriasis was achieved at T90 minutes with a mean (SD) pupillary
      diameter of 6.30 (0.42) mm and 6.35 (0.41) mm in the right eye and left eye,
      respectively. At the dose used, rocuronium bromide induced a consistent bilateral
      simultaneous mydriasis without noticeable adverse effects, and it can be
      considered a reliable and safe topical mydriatic agent in kestrels.

PMID- 22645833
TI  - Marbofloxacin disposition after intravenous administration of a single dose in
      wild mallard ducks (Anas platyrhynchos).
AB  - Marbofloxacin, a fluoroquinolone developed specifically for veterinary use, has
      demonstrated considerable pharmokinetic variation among avian species. The goal
      of this study was to determine the disposition kinetics of marbofloxacin in
      mallard ducks (Anas platyrhynchos) after a single intravenous injection. Six wild
      mallard ducks were used in the study. Marbofloxacin was injected at a dose of 2
      mg/kg into the basilic vein, and blood was subsequently collected at regular
      intervals from each bird. Plasma marbofloxacin concentrations were determined by
      using high-performance liquid chromatography. The volume of distribution at
      steady state was 1.78 +/- 0.37 L/kg, and the total plasma clearance was 0.59 +/-
      0.08 L/kg per hour. Marbofloxacin had a relatively short permanence, with a
      elimination half-life of 2.81 +/- 1.20 hours, a terminal half-life of 2.43 +/-
      0.61 hours, and a mean residence time of 2.99 +/- 0.52 hour. The maximum observed
      concentration (Cmax) and area under the curve (AUC) were 1.34 +/- 0.27 microg/mL
      and 3.75 +/- 0.56 microg x h/mL, respectively. Values of minimum inhibitory
      concentration (MIC), Cmax, and AUC have been used to predict the clinical
      efficacy of a drug in treating bacterial infections, with a Cmax: MIC value of 10
      and an AUC: MIC ratio of 125-250 associated with optimal bactericidal effects. By
      using the study data and MIC breakpoints of 0.125 microg/mL or 0.2 microg/mL,
      values derived for Cmax: MIC were 9.37 +/- 0.99 and 5.85 +/- 0.62, respectively,
      and for AUC: MIC were 29.99 +/- 4.51 and 18.74 +/- 2.82, respectively. By using
      MIC values of 0.125 and 0.2 microg/mL and a target AUC: MIC = 125, the calculated
      optimal daily marbofloxacin dosages for mallard ducks were 9.24 and 14.78 mg/kg,
      respectively. These results suggest that, primarily because of the high total
      plasma clearance observed, the marbofloxacin dose for treatment of bacterial
      diseases in mallard ducks should be increased after intravenous administration.
      Intravenous doses of 10-15 mg/kg should be assessed by studying their potential
      toxicity and efficacy in sick birds.

PMID- 22645834
TI  - Aneurysmal bone cyst on the carpus of an African collared dove (Streptopelia
      roseogrisea).
AB  - An adult female African collared dove (Streptopelia roseogrisea) was presented
      for examination of a mass on the medial surface of the left wing. The mass had
      been present for 2 months but had grown rapidly over the previous 2 weeks. One
      week after presentation, the mass was surgically excised and the involved alular
      bone was removed. Results of histologic examination of the mass were consistent
      with an aneurysmal bone cyst. No underlying factor could be found in this case.
      The wound healing was uneventful, and no mass recurrence was observed during the
      following year. To our knowledge, this is the first report of an aneurysmal bone
      cyst in a columbiform bird.

PMID- 22645835
TI  - Magnesium therapy in a hypocalcemic African grey parrot (Psittacus erithacus).
AB  - Hypocalcemic-induced seizure activity is a clinical entity that is commonly
      diagnosed in neurologic African grey parrots (Psittacus erithacus). Plasma
      calcium levels are typically less than 6.0 mg/dL at the time of seizure activity,
      and although the underlying cause of the hypocalcemia has not yet been
      determined, many theories have been proposed. An African grey parrot that had
      been fed a seed diet for 8 years was presented with hypocalcemia and seizures and
      exhibited precipitously declining plasma calcium levels, despite aggressive
      calcium and vitamin A, D, and E supplementation for 4 days. Baseline magnesium
      levels in this parrot were determined to be 1.9 mg/dL; therefore, magnesium
      sulfate was administered at a dose of 20 mg/kg IM once. Twenty-four hours after
      supplementation, the plasma magnesium level was 3.3 mg/dL, and no further seizure
      activity was observed. We believe that a primary dietary magnesium deficiency may
      have been present in this African grey parrot, similar to a syndrome in leghorn
      chicks, which is frequently characterized by progressive hypocalcemia that is
      unable to be corrected by calcium supplementation alone.

PMID- 22645836
TI  - Neuronal ceroid lipofuscinosis in a mallard duck (Anas platyrhynchos).
AB  - A 3-year-old male, hybrid mallard duck (Anas platyrhynchos) was presented with a
      2-year history of progressive, ascending paresis and paralysis. On presentation,
      the bird was in sternal recumbency and displayed intermittent focal seizures and
      intention tremors. Proprioceptive deficits and absent withdrawal reflexes were
      observed in both pelvic limbs, wing extension was limited, and reflexes were
      diminished bilaterally. Other findings included emaciation and dehydration.
      Results of a complete blood count and plasma biochemical analysis revealed
      anemia, hypoproteinemia, hypoglycemia, and hyperuricemia. Radiographs were
      unremarkable and results of an Aspergillus antibody were weakly positive. The
      duck went into cardiopulmonary arrest and died approximately 1 hour after
      initiating treatment with intravenous crystalloid fluids. A postmortem diagnosis
      of neuronal ceroid lipofuscinosis (NCL) was made based on the presence of
      neuronal granular cytoplasmic material that was autofluorescent and stained with
      periodic acid-Schiff and Luxol fast blue. To our knowledge, this is only the
      second case report of NCL in an avian species and the first in waterfowl.

PMID- 22645837
TI  - Cutaneous mast cell tumor and mastocytosis in a black-masked lovebird (Agapornis
      personata).
AB  - A 12-year-old female black-masked lovebird (Agapornis personata) with a cobalt
      color mutation was presented for self-mutilation of a mass located on the right
      lateral neck. Cytologic evaluation of the soft tissue mass revealed a
      predominance of poorly stained mast cells with metachromatic intracytoplasmic
      granules. The presumptive diagnosis was cutaneous mast cell tumor. Clinical
      evaluation, results of a complete blood cell count and biochemical analysis, and
      radiographs did not reveal systemic manifestation of mast cell disease. The mass
      was surgically resected, but surgical margins were limited because of the
      location of the mass and the small size of the patient. The lovebird died the day
      after surgery. Gross postmortem examination revealed splenomegaly, multifocal
      pinpoint white nodules throughout the liver parenchyma, severe thickening and
      yellow coloration of the great vessels, and pale pink swelling of the caudal
      right kidney. Histopathologic analysis of the resected mass revealed sheets of
      round cells that contain metachromatic granules, defined as neoplastic mast
      cells, within a fine fibrovascular stroma. Similar neoplastic cells were seen in
      the right kidney, hepatic sinusoids, splenic pulp, periovarian connective tissue,
      and bone marrow. The histopathologic diagnosis was a cutaneous mast cell tumor
      and disseminated mast cell disease, or mastocytosis. To the authors' knowledge,
      this is the first reported case of a cutaneous mast cell tumor and mastocytosis
      in a psittacine bird.

PMID- 22645838
TI  - Filarial tenosynovitis caused by Pelecitus species (Spirurida, Filarioidea,
      Onchocercidae) in the legs of a channel-billed toucan (Ramphastos vitellinus).
AB  - An adult channel-billed toucan (Ramphastos vitellinus), imported from Surinam,
      South America, 18 months earlier, was found dead in its cage. At necropsy, the
      hock joints were swollen bilaterally and had a reduced range of motion. Small
      curled worms were present in subcutaneous tissue around the joints, with edema
      and fibrin formation. These worms were classified as the filarioid nematode,
      Pelecitus species. Blood-borne microfilariae were seen in cytologic impression
      smears of the lung and the leg lesions.

PMID- 22645839
TI  - Taking stock in the new year: what would you change?

PMID- 22645840
TI  - What is your diagnosis? Chronic lymphocytic leukemia.

PMID- 22645841
TI  - Moving on up: Structuring career ladders for employee advancement.

PMID- 22645842
TI  - Training coders to transition to ICD-10.

PMID- 22645843
TI  - System-wide flow initiative slashes patient wait times in the ED, boosts volume
      by 25%.
AB  - Emergency department administrators at Cambridge Health Alliance, a three
      hospital health care organization in Cambridge, MA, implemented a system-wide
      flow initiative that has reduced the average length-of-stay for rapid assessment
      patients from three hours to just over an hour. Under the approach, patients are
      immediately placed in a room, and providers and registration staff come to the
      patients rather than the traditional approach of having patients constantly move
      from place to place with wait times in between each interval of care. The
      approach relies on "patient partners," non-clinical personnel who are trained in
      customer service, to greet and quick-register patients who present to the ED for
      care. Administrators say 97% of patients who present to the ED are in a room
      within five minutes, and over 90% of them are seen by a provider within 14
      minutes. The leave-without-being-seen (LWBS) rate has been slashed from 4.5% to
      0.6%. System-wide ED volume, which was dropping before the new approach was
      implemented, has gone from 77,000 patients per year to nearly 100,000 patients
      per year.

PMID- 22645844
TI  - Leverage front-line expertise to maximize trauma prevention efforts.
AB  - The trauma prevention program at Geisinger Wyoming Valley (GWV) Medical Center in
      Wilkes-Barre, PA, has enlisted the assistance of an experienced paramedic and ED
      tech to spend part of his time targeting prevention education toward populations
      that have been experiencing high rates of traumatic injuries. While community
      outreach has long been a priority for the trauma prevention program, the new
      position is enabling GWV to boost the magnitude of its prevention efforts, and to
      reach out to referring facilities as well. Program administrators say a similar
      outreach effort aimed at EMS providers has strengthened relationships and helped
      to improve trauma care at the facility. The new trauma injury prevention outreach
      coordinator has focused his first efforts on fall prevention and curbing motor
      vehicle accidents among very young and very mature driving populations. Data from
      GWV's trauma registry suggest that its fall prevention efforts are having an
      effect. The incidence of falls among patients over the age 65 is down by about
      10% at the facility since it began targeting education at the community's senior
      population. Administrators say a monthly lecture series aimed at the prehospital
      community has gone a long way toward nurturing ties with EMS providers. Called
      "EMS Night Out," the series covers a range of topics, but the most popular
      programs involve case reviews.

PMID- 22645845
TI  - Real-time tracking data drive process improvements, even while ED volumes
      continue to climb.
AB  - Christiana Hospital in Newark, DE, has been able to dramatically reduce length-of
      stay in the ED by making use of data derived from a real-time location system
      (RTLS) that tracks the movements of patients, providers, and staff.
      Administrators say that while some efficiencies are gained from the system alone,
      most of the positive impact is derived from using the RTLS data to focus on
      specific processes and make refinements. Within one year of implementing the RTLS
      technology, LOS in the ED was reduced by 40 minutes for admitted patients and 18
      to 20 minutes for the treated-and-released population. A work group focused on
      process improvements in the ED's fast track section reduced the average LOS from
      2.5 hours to 60 minutes or less. Similarly, a work group focused on the ESI 3
      population reduced the average treatment time for this population from 5 or 6
      hours to 3.4 hours. Administrators say key steps toward a successful RTLS
      implementation are careful planning for how you want to use the technology, and
      alleviating staff concerns about why their movements are being tracked.

PMID- 22645846
TI  - Computational finite element analyses to optimize graft sizing during aortic
      valve-sparing procedure.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic valve-sparing (AVS) procedures have been
      introduced to treat ascending aorta dilatation and aortic valve insufficiency in
      the presence of preserved native aortic valve leaflets. Although the surgical
      technique has been standardized, the choice of best type and size of Dacron graft
      to be used remains a matter of debate. Herein are presented preliminary results
      based on a patient-specific finite element model aimed at optimizing the Dacron
      prosthesis size and shape. Previously, finite element analysis (FEA) has been
      applied to investigate medical problems and, in particular, to better evaluate
      the pathophysiology of the aortic root. To date, however, such methodology has
      not been applied to the patient-specific evaluation of AVS postoperative results.
      METHODS: The framework of the FEA study included four steps: (i) the creation of
      a mathematic model of the patient's aortic root; (ii) the creation of a model for
      two different Dacron grafts (the standard straight graft and a Valsalva graft),
      with sizes of each type ranging from 24 to 30 mm; (iii) a virtual computer-based
      simulation of the AVS procedure, using each graft; and (iv) a virtual computer
      based simulation of the diastolic closure of the repaired valve and an evaluation
      of post-implant physiology, based on three parameters: the height of coaptation
      ratio (H(C)R); the length of coaptation ratio (L(C)R); and the distance between
      the central point of coaptation and the ideal geometrical centre (D(C)). RESULTS:
      The simulation results of post-implant performance of the aortic valve revealed
      that both H(C)R and L(C)R were decreased as the graft size was increased, but no
      significant differences were identified between two types of graft. In contrast,
      the Valsalva graft, when compared to the standard straight graft, led to a
      significant reduction in D(C). The results in terms of H(C)R, L(C)R and D(C)
      recommended unequivocally, for the specific case under investigation, that a 30
      mm straight graft and a 28 mm Valsalva graft would ensure the most physiological
      valve behavior for the patient under investigation. CONCLUSION: In evaluating the
      potential of a preoperative prediction of the optimal graft size, using FEA, the
      virtual simulation of the AVS procedure proved to be feasible and useful in
      predicting the postoperative physiology of the aortic root. In particular, this
      finite element model might have a clinical impact as may be used to optimize the
      surgeon's choice of prosthesis size.

PMID- 22645847
TI  - Conventional aortic valve replacement remains a safe option in patients aged > or
      = 70 years: a 20-year experience.
AB  - BACKGROUND AND AIM OF THE STUDY: Increased life expectancy has resulted in the
      elderly frequently presenting with severe aortic stenosis. It has therefore
      become important to define indications for conventional aortic valve replacement
      (AVR) and transcatheter aortic valve implantation (TAVI) in this patient
      population. Thus, patients aged > or = 70 years undergoing conventional isolated
      AVR were evaluated for predictors of early and late mortality. METHODS: A
      retrospective analysis was conducted of prospectively collected data available
      from 1,061 consecutive patients (age range: 70-94 years) who underwent isolated
      AVR between 1982 and 2002. The patient age groups were 70-74 years (n = 466), 75
      79 years (n = 367), and > or = 80 years (n = 228). The mean follow up was 6.0 +/-
      4.4 years, and the total follow up 6,390 patient-years. Twenty-two variables were
      considered as potential risk factors for early and late mortality. RESULTS: Early
      mortality was higher in patients aged > or = 80 years than in those aged 70-79
      years. Early mortality in patients aged > or = 80 years was lower between 1998
      and 2002 than between 1982 and 1997. Multivariate predictors of early mortality
      were age > or = 80 years, operative status, previous intervention, renal failure,
      and mitral regurgitation. The early nonfatal complication rate was similar for
      patients aged 70-79 years and > or = 80 years, but late mortality was lower
      between 1998 and 2002 than between 1982 and 1997 in patients aged 70-79 years,
      and in those aged > or = 80 years. The 10-year actuarial survivals after AVR in
      patients aged 70-74, 75-79, and > or = 80 years were 54 +/- 3.0%, 43 +/- 3.8% and
      17 +/- 3.9%, respectively. Multivariate predictors of late mortality were age 75
      79 years, age > or = 80 years, peripheral vascular disease (PVD) and chronic
      obstructive pulmonary disease (COPD). Female gender was shown to be protective.
      CONCLUSION: Early mortality was higher in patients aged > or = 80 years
      undergoing AVR, though this has declined recently and is currently at an
      acceptable level. Other important predictors of mortality in elderly patients
      undergoing AVR are operative status, previous interventions, renal failure,
      mitral regurgitation, male gender, PVD, and COPD. Thus, conventional AVR remains
      a safe treatment option for the elderly patient.

PMID- 22645848
TI  - Critical aortic stenosis: one more vulnerable group for patient-prosthesis
      mismatch.

PMID- 22645849
TI  - Impact of aortic stenosis severity and its interaction with prosthesis-patient
      mismatch on operative mortality following aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: The optimal timing of aortic valve replacement
      (AVR) in patients with severe aortic stenosis (AS) is a source of debate.
      Moreover, it has been shown previously that prosthesis-patient mismatch (PPM) is
      an independent predictor of operative mortality after AVR. The study aim was to
      assess the effect of the preoperative severity of AS and its interaction with PPM
      with respect to operative mortality after AVR. METHODS: The data were analyzed
      from 2,104 consecutive patients who had undergone AVR for severe AS. The patients
      were allocated to tertiles according to their preoperative indexed aortic valve
      area (AVAi) as: < 0.35 cm2/m2, 0.35 to 0.43 cm2/m2, and > 0.43 cm2/m2. PPM was
      defined as a projected postoperative indexed effective orifice area (EOAi) of the
      implanted prosthesis < 0.85 cm2/m2. RESULTS: The operative mortality was 5.7% (n
      = 120). On multivariate analysis, an independent association was identified
      between the preoperative severity of AS and operative mortality (odds ratio [OR]
      = 2.00, p = 0.03 for AVAi < 0.35 cm2/m2; OR = 1.39, p = 0.32 for AVAi 0.35-0.43
      cm2/m2). Notably, the impact of PPM was more important in patients with more
      severe AS (p = 0.046 for AVAi x EOAi interaction). CONCLUSION: The study results
      confirmed that very severe AS (AVAi < 0.35 cm2/m2) is independently associated
      with operative mortality after AVR. The results also emphasized the importance of
      avoiding PPM in these patients.

PMID- 22645850
TI  - Sutureless aortic valve replacement through a right minithoracotomy.
AB  - During the past decade, interest in the development of less-invasive cardiac
      valve surgery has undergone a steady increase, with many surgeons having
      supplanted full sternotomy with minimal-access incisions. While the minimally
      invasive approaches for the treatment of mitral disease have been standardized,
      the preferred route for aortic valve replacement (AVR) remains a matter of
      debate. Although AVR through a right minithoracotomy avoids opening the sternum,
      it does require a greater surgical ability and may be a challenging procedure,
      even for expert surgeons. By simplifying the valve implantation, the availability
      of sutureless prostheses might provide an important incentive for the diffusion
      of this approach. Herein are reported the details of three patients who received
      a 3f-Enable sutureless aortic bioprosthesis via a right minithoracotomy. The
      advantages and possible improvements of this procedure are also discussed.

PMID- 22645851
TI  - An acute animal model of aortic stenosis: initial attempts at leaflet
      modification.
AB  - BACKGROUND AND AIM OF THE STUDY: Percutaneous valve insertion is an emerging
      treatment for aortic stenosis (AS). To date, no large animal model exists that
      replicates human calcific AS; moreover, the absence of any valve pathology in
      currently available animal models prevents their use in any realistic assessment
      of percutaneous aortic valve therapy. Hence, the aim of the present study was to
      create an acute large animal model in which human calcific AS could be simulated.
      METHODS: Ten domestic swine underwent open-heart surgery utilizing
      cardiopulmonary bypass (CPB) and cardioplegic arrest. The aortic valve annulus
      and leaflets were injected with cyanoacrylate, after which epicardial
      echocardiography was used to assess the creation of AS. At the time of animal
      sacrifice, the hearts were harvested for gross and histopathological examination.
      RESULTS: The leaflet and annular injections were performed successfully in all
      animals. Subsequently, seven animals were weaned from CPB and underwent post
      procedural echocardiographic evaluations, whereby the treated valves were
      harvested for gross and histological examination. CONCLUSION: Cyanoacrylate can
      be injected into the porcine aortic valve and annulus to create a model that
      resembles human calcific AS in the acute setting. Additional long-term follow up
      studies must be conducted, however, before this model can be utilized in the
      development of percutaneous valve therapy.

PMID- 22645852
TI  - Valve-sparing aortic root replacement for patients with a Fontan circulation.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic root aneurysm is an emerging disease
      related to the treatment of patients with hypoplastic left heart syndrome (HLHS)
      and other single-ventricle physiology. The authors' experience with valve-sparing
      aortic root replacement and concomitant procedures in patients with a single
      ventricle was reviewed. METHODS: Four patients aged 11 to 19 years presented with
      progressive aortic root dilatation. All had undergone a Fontan completion: two
      patients for HLHS, one patient for tricuspid valve atresia, and one for pulmonary
      atresia with a ventricular septal defect. Two patients developed more than grade
      2+ aortic valve insufficiency, and one patient developed symptomatic left
      anterior descending coronary artery compression. The preoperative root dimension
      ranged from 38 to 56 mm (mean 45mm). A valve-sparing aortic root replacement,
      annular reduction and ascending aorta replacement was performed in all patients.
      Two patients underwent a Fontan revision, two an aortic valve repair, and one
      patient a tricuspid valve repair. RESULTS: At a mean follow up of 2.6 years, all
      four patients were in NYHA functional class I. Two patients underwent neo-aortic
      valve replacement at about two years after aortic root replacement and valve
      repair, as they had developed severe neo-aortic valve insufficiency. Both of
      these patients had HLHS. In the other two patients, the most recent
      echocardiography demonstrated grade 0 to 1+ aortic insufficiency, with good
      function of the single ventricle. CONCLUSION: Aortic root reimplantation is an
      effective treatment for aortic root dilatation in patients with a single
      ventricle. However, if associated with significant aortic insufficiency, then a
      long-term freedom from valve replacement is questionable.

PMID- 22645853
TI  - Aortic root distensibility after subcoronary stentless valve implantation.
AB  - BACKGROUND AND AIM OF THE STUDY: The preservation of aortic root dynamics is
      considered important for the durability of aortic valve bioprostheses. Stentless
      heart valves are believed to support physiologic biomechanics. To date, dynamic
      analysis has been limited to the full root prosthesis, and exclusively in the
      radial direction. The study aim was to investigate and compare the radial and
      longitudinal aortic root distensibilities of subcoronary stentless valves, and of
      stented and native pig valves. METHODS: Stented pericardial (Mitroflow) or
      stentless (Solo, Toronto SPV) valve prostheses, or native porcine valves, were
      investigated in 32 pigs. Postoperatively, 12 sonomicrometry crystals were placed
      on the aortic root in order to measure aortic root distensibility, in both radial
      and longitudinal directions. RESULTS: Sonomicrometry data were obtained from 23
      pigs (72%). At the annular level, the native and Solo valves were significantly
      more distensible in a radial direction than the Mitroflow valve (p = 0.04).
      However, at the level of the sinotubular junction (STJ), commissures and aorta,
      the native valve was significantly more distensible than all of the artificial
      valves (p = 0.006, p = 0.006, and p = 0.02, respectively). The Solo valve
      exhibited less longitudinal distensibility than the Toronto SPV and Mitroflow
      valves. The Toronto SPV initiated a radial expansion at the STJ significantly
      later in the cardiac cycle than did both the Solo and native valves (p = 0.03),
      but showed no difference compared to the Mitroflow valve. Longitudinal expansion
      between the annulus and the STJ started significantly earlier for the Solo valve
      than for both the Toronto SPV (p = 0.03) and Mitroflow (p = 0.02) valves.
      CONCLUSION: The Solo valve proved to be superior in maintaining annular
      distensibility immediately following implantation when compared to the Mitroflow
      valve. The Solo valve did not, however, preserve longitudinal distensibility as
      well as the other investigated valves. Finally, the Solo valve appeared to
      provide a more physiologic aortic root expansion pattern than its prosthetic
      counterparts.

PMID- 22645854
TI  - Aortic elastic properties and left ventricular diastolic function in patients
      with isolated bicuspid aortic valve.
AB  - BACKGROUND AND AIM OF THE STUDY: Bicuspid aortic valve (BAV) is one of the most
      common congenital heart defects. BAV disease is not only a disorder of
      valvulogenesis, but also represents a genetic disorder of aorta and cardiac
      development. Recent studies have shown that BAV is associated with abnormal
      aortic elasticity, and that a reduced distensibility of the aortic root may have
      a negative impact on left ventricular function. Hence, the study aim was to
      investigate left ventricular diastolic function and its relationship to aortic
      elasticity in this patient group. METHODS: Thirty-nine patients with isolated BAV
      with a normal left ventricular ejection fraction, and 29 age- and gender-matched
      healthy (control) subjects, were studied prospectively. In none of the patients
      with BAV was the aortic velocity >2m/s, and no aortic regurgitation (other than
      mild) was present. Parameters of aortic elasticity (aortic strain, distensibility
      index, stiffness index and elastic modulus), left ventricular diastolic
      parameters (E, A, E/a, deceleration time, E', ratio of E/E', left atrial volume
      index) and valvulo-arterial impedance were calculated in all patients. RESULTS:
      Aortic strain and distensibility were lower, and aortic stiffness index and
      aortic modulus higher, in patients with BAV than in controls. Compared to
      controls, the E/E' ratio and left atrial volume index were significantly higher
      in BAV patients (E/E' ratio 8.26 +/- 2.56 versus 6.85 +/- 1.45, p = 0.01; left
      atrium volume index 24.23 +/- 5.78 versus 21.68 +/- 4.11 ml/m2, p = 0.04).
      However, no significant correlations were identified between the aortic
      elasticity parameters, valvulo-arterial impedance, and left ventricular diastolic
      parameters. CONCLUSION: These findings indicated that BAV is associated with an
      increased left atrial volume and a decreased E/E' ratio. In addition, these
      parameters did not correlate with any parameters of aortic elasticity, nor
      valvulo-arterial impedance. These data suggest that BAV disease might have
      subclinical cardiac dysfunction, and further studies are required to confirm
      these findings and any causal relationship.

PMID- 22645855
TI  - Mid-term results of different aortic valve-sparing procedures in Marfan syndrome.
AB  - BACKGROUND AND AIM OF THE STUDY: Marfan patients with aortic root aneurysm are
      typically treated with the Bentall procedure, though aortic valve-sparing
      procedures (AVSPs) are also possible. The study aim was to compare the authors'
      experience with two such techniques performed at their institution, namely a
      reimplantation according to David (David I) and remodeling according to Yacoub.
      METHODS: Between 1996 and 2009, a total of 37 Marfan patients underwent an AVSP
      at the authors' institution. Of these patients, 25 (mean age 32 +/- 14.9 years)
      underwent surgery according to David (group D), and 12 (mean age 35 +/- 10.9
      years) according to Yacoub (group Y). The patients underwent both clinical and
      echocardiographic follow up examinations at a mean of 42.0 +/- 36.4 months after
      surgery. RESULTS: One patient from each group had moved abroad and was lost to
      follow up. The remaining 35 patients were alive at follow up, and none presented
      with any major neurological or bleeding complications. In addition, no
      significant differences were noted between the groups in terms of NYHA
      classification, left ventricular function, or left ventricular diameter. At
      follow up, aortic valve function was also comparable between groups, with a
      peak/mean gradient of 9.4 +/- 6.4/5.3 +/- 3.5 mmHg and 5.1 +/- 3.3/2.8 +/- 1.5
      mmHg for groups D and Y, respectively (p = 0.081/0.058). The measured mean grades
      of aortic valve regurgitation were comparable in groups D and Y (0.6 +/- 0.7 and
      1.1 +/- 0.6, respectively; p = 0.055). However, aortic root dimensions obtained
      via M-mode were smaller in group D patients (29.6 +/- 2.3 mm) than in group Y
      patients (36.1 +/- 6.6 mm) (p = 0.027). Only three patients from group Y required
      reoperation on the aortic valve due to valvular regurgitation (p = 0.028); two of
      these had presented with aortic dissection at the first operation. CONCLUSION:
      Both types of AVSP can be performed with comparably good interim clinical
      results, and also low mortality and morbidity, in patients with Marfan syndrome.

PMID- 22645856
TI  - Hemodynamic assessment of mitral stenosis: mitral valve resistance as an
      echocardiographic index.
AB  - BACKGROUND AND AIM OF THE STUDY: Although mitral valve (MV) resistance has been
      proposed as a new index for the determination of hemodynamic consequence in
      patients with mitral stenosis (MS), the relationship between this resistance and
      signs of hemodynamic deterioration, such as the elevation of pulmonary artery
      pressure and plasma levels of brain natriuretic peptide (BNP), has not yet been
      investigated. METHODS: The study population comprised 33 consecutive patients
      (nine males, 24 females; mean age 39 +/- 6 years) with moderate and severe MS (MV
      area (MVA) <1.5 cm2). The cause of MS in all patients was rheumatic valvular
      disease. A comprehensive echocardiographic evaluation was performed, with MVA,
      mean MV pressure gradient (MVPG), systolic pulmonary artery pressure (sPAP) and
      mitral valve resistance being calculated for all patients, in addition to plasma
      BNP levels. RESULTS: Both, plasma BNP level and sPAP correlated better with MV
      resistance (r = 0.75, p < 0.001 and r = 0.52, p = 0.002, respectively) than with
      MVA by pressure half-time method (MVA-PHT) (r = -0.68, p < 0.001 and r = -0.55, p
      = 0.001, respectively) and mean MVPG (r = 0.62, p < 0.001 and r = 0.69, p <
      0.001, respectively). A comparison of MV resistance and conventional stenotic
      indices showed that MV resistance correlated best with mean MVPG (r = 0.70, p <
      0.001), and correlated least with MVA-PHT (r = -0.45, p = 0.009). Patients with
      sPAP >50 mmHg and plasma BNP level >150 pg/ml had a significantly higher MV
      resistance than patients with sPAP < 50 mmHg and plasma BNP level <150 pg/ml.
      CONCLUSION: MV resistance appeared to be better correlated with elevated sPAP and
      plasma BNP levels than with conventional stenosis indices.

PMID- 22645857
TI  - Percutaneous closure of mitral paravalvular leaks: a systematic review and meta
      analysis.
AB  - BACKGROUND AND AIM OF THE STUDY: The percutaneous closure of mitral paravalvular
      leak (PVL) is emerging as an alternative treatment for high-risk surgical
      candidates. Several cases have been reported, and a few small studies have been
      conducted to investigate the outcome of the technique. A meta-analysis of the
      combined data would be considered helpful in deriving more powerful data; hence,
      the study aim was to conduct a meta-analysis of the percutaneous closure of
      mitral PVLs, as reported in the medical literature. METHODS: Searches were
      conducted of the PubMed, Embase, and CINAHL databases for reports of mitral PVL
      percutaneous closure. The data were extracted by two reviewers, who aggregated
      the information by using a random-effects model. RESULTS: Eight studies were
      included in the meta-analysis, with a total of 100 patients. The percutaneous
      closure of mitral PVLs was associated with a 15% cardiovascular mortality during
      the first year of follow up. Clinical success was noted in 48% of patients, while
      52% failed to show any clinical improvement. Failures were mainly attributed
      either to deployment failure (18%), to the presence of a persistent leak, to
      hemolysis, or both (31%). Procedure-related complications (e.g., bleeding,
      stroke, endocarditis) were observed in 16% of patients. CONCLUSION: The
      percutaneous closure of mitral PVLs carries a 15% risk of cardiovascular
      mortality. The reported mortality rates for surgically treated patients ranged
      from 12% to 37%, but most patients who underwent percutaneous closure were
      considered high-risk surgical candidates with multiple comorbidities. While
      percutaneous closure appears promising, the development of lesion-specific
      occluders, standardized imaging techniques and parameters, and the design of
      randomized clinical trials to compare the outcome of surgical versus percutaneous
      intervention, are required before any final judgment may be made.

PMID- 22645859
TI  - The effects of dynamic saddle annulus and leaflet length on transmitral flow
      pattern and leaflet stress of a bileaflet bioprosthetic mitral valve.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to determine the effect of
      mitral saddle annulus and leaflet length on peak leaflet stress and transmitral
      flow pattern when utilizing a novel bileaflet bioprosthetic valve. METHODS: A
      novel valve, which closely mimics the saddle annulus motion of the mitral valve
      was developed. A series of computational analyses and in-vitro hemodynamic
      studies was performed to assess the effect of annulus dynamics and leaflet length
      on stress distribution at the leaflet tips as well as the transmitral flow
      pattern downstream of the valve. RESULTS: The analysis showed that the dynamic
      annulus may significantly reduce stress along the tip of the leaflets compared to
      the rigid annulus in a standard trileaflet valve. The leaflet length may also
      significantly alter stress distribution over the leaflets by affecting the
      annulus dynamics. It was shown in vitro that the interaction between the leaflet
      and the ventricular results in fundamentally distinct transmitral vortex
      formation patterns. CONCLUSION: Motion of the mitral saddle annulus along with
      the leaflet length is a critical factor that minimizes stress distribution at the
      tips of the leaflets due to a dampening of the pressure load exerted over the
      valve during the cardiac cycle. The length of the leaflets, and their proximity
      to the ventricular wall, have been shown to have significant effects on
      transmitral vortex formation and energy dissipation during blood transfer from
      the left atrium towards the aorta via left ventricle.

PMID- 22645858
TI  - Persistence of mitral regurgitation following ring annuloplasty: is the papillary
      muscle outside or inside the ring?
AB  - BACKGROUND AND AIM OF THE STUDY: Ischemic mitral regurgitation (IMR) often
      persists, despite annular ring reduction. It has been hypothesized that
      persistent IMR following ring annuloplasty was related to a continued tethering
      of the mitral leaflets, as defined by the distance by which the papillary muscles
      (PMs) were displaced outside the mitral annular ring. METHODS: Seven sheep (four
      acute, three chronic) with persistent mitral regurgitation (MR) following ring
      annuloplasty for IMR were studied using three-dimensional (3D) echocardiography
      to examine the mitral valve geometry. The three stages examined were: Stage 1,
      baseline; Stage 2, post myocardial infarction (via ligation of the obtuse
      marginal branches); and Stage 3, post undersized ring annuloplasty. The 3D
      echocardiography measurements included mitral annular area, tethering distance
      from the ischemic PM to the anterior annulus, and the outside displacement of the
      PM relative to ring PM displacement. RESULTS: Persistent moderate MR remained in
      these seven sheep following undersized ring annuloplasty (MR vena contracta
      change (pre versus post ring): 7.0 versus 5.8 +/- 2.4 mm, p = NS), despite a
      reduction in the mitral annular area of 50 +/- 18% (10.3 +/- 6.3 versus 4.7 +/-
      1.3 cm2). Ring annuloplasty shifted the posterior annulus towards the anterior
      annulus, such that the infarcted PM became displaced outside the mitral annulus.
      The projected displacement distance of the PM outside versus inside the annular
      ring was 8.4 +/- 2.4 mm outside mitral annulus post ring versus 3.6 +/- 2.5 mm
      within mitral annulus pre ring, p < 0001). The displacement distance from the
      infarcted PM to the mitral annulus restricted the ability of the posterior
      leaflet to move anteriorly, preventing effective coaptation. By multivariate
      analysis, this displacement distance was an important determinant of residual MR
      (p < 0.02). CONCLUSION: Persistent MR following ring annuloplasty for IMR relates
      to persistently abnormal leaflet tethering, with restricted posterior leaflet
      motion due to PM displacement outside of the mitral annulus.

PMID- 22645860
TI  - Valvular heart diseases in the developing world: developmental biology takes
      center stage.
AB  - Heart valve disease is a significant and increasing global problem of which, in
      the developing world, the primary sufferers are the children and young adults
      regarded as the critical 'engine' of future economic growth. Yet, up to 10 times
      the current number of known sufferers remain undiagnosed in these countries.
      Among the most prevalent and neglected diseases are rheumatic heart disease and
      endomyocardial fibrosis. The etiologies of these diseases can be described in
      part as a dysregulation or reactivation of developmental biology pathways.
      Consequently, connecting mechanisms of valvulogenesis and disease etiology may
      represent an excellent strategy to identify therapeutic targets. These local
      diseases require local solutions tailored to local resources; therefore,
      collaboration with experienced research groups should be encouraged as a way of
      accelerating the creation of relevant knowledge, and its clinical translation.

PMID- 22645861
TI  - The pathology of TRI-Tech valve leaflet escape.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to investigate leaflet escape
      in the TRI-Tech mechanical valve, as reported in three patients. METHODS: Among
      the three patients, one patient with a mitral prosthesis from which leaflet
      escape occurred underwent a successful reoperation. However, two patients with an
      aortic prosthesis from which leaflet escape occurred died suddenly. In addition,
      150 unimplanted TRI-Tech valve prostheses were evaluated. RESULTS: Tab fracture
      was observed in all of the escaped leaflets, with a height asymmetry of 0.33 mm
      in the mitral valve, and 0.55 and 0.41 mm, respectively, in the two aortic
      valves. Height tab asymmetry was present in all unimplanted valves: this was
      <0.20 mm in 90% of valves, and >0.20 mm in 10% (in one valve the asymmetry was
      >0.35 mm). Height asymmetry was greatest in valves sized 21 to 25 mm. A review of
      data provided by the TRI-Tech quality control unit failed to demonstrate any
      reference to checking for tab symmetry. CONCLUSION: Significant tab malalignment
      was observed in the TRI-Tech valves in which tab fracture and leaflet escape had
      occurred. Tab asymmetry was also present in all unimplanted valves; this was
      >0.20 mm in 10% of units, and in one case was as high as in valves that had
      undergone leaflet escape. As tolerance for tab asymmetry is unknown and the risk
      of rupture is unpredictable, an interruption of the implant program with
      prophylactic replacement of the implanted TRI-Tech valves must be considered
      judicious.

PMID- 22645863
TI  - The role of the sewing ring in tissue healing: a pathologic study of explanted
      mechanical heart valves.
AB  - BACKGROUND AND AIM OF THE STUDY: Serious complications may occur after heart
      valve replacement, and many such patients will require reoperation. The study aim
      was to identify the pattern of tissue response around the sewing ring of those
      valves that have been explanted as a result of various valve-associated
      complications. METHODS: A total of 51 mechanical heart valves (MHVs) was
      explanted from 45 patients who had undergone reoperation for valve-related
      complications. The examination of the valves included an analysis of the
      operative findings, macroscopic findings, histopathology, and dissection of the
      sewing ring. RESULTS: The extent of tissue hyperplasia was variable around the
      sewing rings of valves explanted for various pathologies. In pannus, the
      hyperplastic tissue extended into the valve orifice and produced an obstruction
      to flow, whereas in thrombosed valves the thrombus was attached to the tissue at
      the annulus. In non-infective pathologies, the histology revealed cellular
      infiltration that was limited to the peripheral fabric layers of the sewing ring,
      though the extent of infiltration was not increased with the duration of
      implantation. In prosthetic valve endocarditis (PVE), the surrounding
      hyperplastic tissue was granulomatous, but cellular infiltration into the sewing
      ring was absent. The dissection of various models of explanted valves revealed
      that different types of filler and fixing mechanisms had increased the bulk of
      the sewing ring. CONCLUSION: Tissue hyperplasia of varying extent occurs around
      the sewing ring after MHV implantation. The cellular elements grow into the
      peripheral layers, but not the deeper layers, of the sewing ring. In PVE, there
      was an absence of cellular infiltration into the sewing ring.

PMID- 22645864
TI  - Pasteurella multocida endocarditis.
AB  - Pasteurella multocida is a Gram-negative rod that forms part of the natural oral
      flora of cats and dogs. It is usually associated with skin and soft tissue
      infections, as a result of bites and scratches. Although invasive and serious
      infections by P. multocida are rare, there are limited reports of pneumonia and
      sepsis. Infective endocarditis (IE) is extremely rare. The case is reported of an
      82-year-old male who presented with a productive cough, fever, and shortness of
      breath, and who was initially diagnosed with pneumonia. Further work-up revealed
      P. multocida bacteremia and an aortic valve lesion consistent with endocarditis.
      The patient was treated with antibiotics, and showed significant clinical
      recovery on follow up.

PMID- 22645862
TI  - An ovine model of pulmonary insufficiency and right ventricular outflow tract
      dilatation.
AB  - BACKGROUND AND AIM OF THE STUDY: The treatment of pulmonary insufficiency (PI)
      following reconstructive surgery of the right ventricular outflow tract (RVOT) in
      repair of the tetralogy of Fallot remains a significant challenge. The study aim
      was to establish an ovine model of dilated RVOT and PI, and to quantify the
      degree of PI and right ventricular remodeling over an eight-week period, using
      magnetic resonance imaging (MRI). METHODS: Five sheep underwent baseline MRI
      scanning and catheterization. The weight-indexed right and left ventricular end
      diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection
      fraction (EF) and pulmonary regurgitant fraction (RF) were measured at baseline.
      The animals then underwent pulmonary valvectomy and transannular patch repair of
      the RVOT. Repeat MRI and hemodynamic measurements were obtained after an eight
      week period. RESULTS: The indexed RVEDV increased from 49 +/- 4.0 ml/m2 at
      baseline to 80 +/- 10.3 ml/m2 at eight weeks after valvectomy (p = 0.01), while
      the indexed RVESV increased from 13 +/- 3.4 ml/m2 to 33 +/- 8.8 ml/m2 (p = 0.01).
      The indexed RVSV increased from 36 +/- 3.7 ml/m2 to 47 +/- 1.7 ml/m2 (p = 0.01).
      The RVEF at baseline was 74 +/- 6%, and this decreased to 59 +/- 5% at follow up
      (p = 0.02). The RF at baseline was 0 +/- 0% and was increased to 37 +/- 3% at
      eight weeks after valvectomy (p < 0.001). The left ventricular (LV) function was
      also diminished: LVEF at baseline was 67 +/- 2%, versus 49 +/- 10% at follow up
      (p = 0.01). Both, the RV and LV end-diastolic pressures were significantly
      elevated at follow up. CONCLUSION: All five animals developed pulmonary
      regurgitation sufficient to cause significant RV dilatation and diminished RV and
      LV functions. This model may be used to investigate novel therapeutic approaches
      in the treatment of this difficult clinical problem.

PMID- 22645865
TI  - An interrupted suture technique for ascending aortic replacement concomitant to
      aortic valve repair.
AB  - While running suture anastomoses represent the mainstay of thoracic aortic
      surgery, advantages may exist for interrupted techniques in selected cases,
      especially with ascending aortic replacement and concomitant aortic valve repair.
      Interrupted suture anastomoses precisely reconstruct the sinotubular geometry in
      dissections, and allow the proximal suture line to be placed close to the
      coronary arteries and aortic valve posts. With aneurysm extension into the aortic
      arch, interrupted suture techniques allow hemi-arch replacement without the need
      for aortic clamp removal and circulatory arrest. By 'sandwiching' all layers of
      the aortic wall between a Dacron graft on the inside and a Teflon strip on the
      outside, quite hemostatic anastomoses can be performed, even with poor-quality
      tissues. Any tearing of the aortic wall adjacent to individual sutures will not
      loosen the entire suture line, and can be repaired simply by extra suture
      placement. Thus, in selected situations, interrupted suture methods can be useful
      for ascending aortic replacement.

PMID- 22645866
TI  - Double freestyle valve replacement in a patient with a prior Ross procedure.
AB  - Following a Ross procedure, patients may require reintervention for valvular
      stenosis or insufficiency of either the pulmonary autograft or the pulmonary
      homograft. Herein is reported a double use of the Medtronic Freestyle stentless
      bioprosthesis in a patient who previously had undergone a Ross procedure.

PMID- 22645867
TI  - Tricuspid valvar regurgitation in congenital absence of the pericardium.
AB  - Congenital absence of the pericardium (CAP) is a rare disorder in which most
      patients are asymptomatic. The association between this condition and the
      development of significant tricuspid valvar regurgitation (TR) has been reported,
      but the causal relationship between them is not clear. Herein is provided a
      review of all reported cases of CAP associated with TR, and the potential
      pathogenetic mechanisms behind this association are discussed. Finally, it is
      suggested that blunt chest trauma might play be a link between these two isolated
      findings.

PMID- 22645868
TI  - Mitral regurgitation as a late complication of stroke prevention by the WATCHMAN
      device.

PMID- 22645869
TI  - Lambl's excrescence: recapitulation of a human phenotype in a mouse.

PMID- 22645870
TI  - Increasing numbers of suicide within the Army has been a growing problem for the
      last ten years paralleling the Wars in Iraq and Afghanistan.

PMID- 22645871
TI  - Is there a role for peer support delivered interventions in the treatment of
      veterans with post-traumatic stress disorder?

PMID- 22645872
TI  - Practice guidelines for the diagnosis and management of patients with Q fever by
      the Armed Forces Infectious Diseases Society.
AB  - This issue in the series Current Topics in Military Tropical Medicine focuses on
      Q Fever. Q fever is a zoonotic infection caused by the bacterium Coxiella
      burnetii. Over 150 confirmed cases have occurred among U.S. military personnel
      deployed to Iraq since 2007. Acute Q fever is underdiagnosed because of a myriad
      of possible clinical presentations but typically presents as a flu-like illness.
      The most common chronic manifestation is endocarditis. Most providers are not
      familiar with the diagnosis, treatment, or appropriate follow-up of this disease.
      In order to facilitate the care of patients infected with C. burnetii, the Armed
      Forces Infectious Diseases Society convened a panel of experts in the field to
      develop practical guidelines for those caring for infected patients. The
      recommendations and rationale are reviewed in this article.

PMID- 22645873
TI  - Chemical terrorism for the intensivist.
AB  - The use of chemical agents for terrorist attacks or military warfare is a major
      concern at the present time. Chemical agents can cause significant morbidity, are
      relatively inexpensive, and are easy to store and use. Weaponization of chemical
      agents is only limited by the physicochemical properties of some agents. Recent
      incidents involving toxic industrial chemicals and chemical terrorist attacks
      indicate that critical care services are frequently utilized. For obvious
      reasons, the critical care literature on chemical terrorism is scarce. This
      article reviews the clinical aspects of diagnosing and treating victims of
      chemical terrorism while emphasizing the critical care management. The
      intensivist needs to be familiar with the chemical agents that could be used in a
      terrorist attack. The military classification divides agents into lung agents,
      blood agents, vesicants, and nerve agents. Supportive critical care is the
      cornerstone of treatment for most casualties, and dramatic recovery can occur in
      many cases. Specific antidotes are available for some agents, but even without
      the antidote, aggressive intensive care support can lead to favorable outcome in
      many cases. Critical care and emergency services can be overwhelmed by a
      terrorist attack as many exposed but not ill will seek care.

PMID- 22645874
TI  - Mental health care use by soldiers conducting counterinsurgency operations.
AB  - Counterinsurgency (COIN) has become the cornerstone of the military's strategy to
      combat terrorist threats. COIN operations are complex and often expose soldiers
      to unfamiliar stressors as they fight the enemy while developing and maintaining
      rapport with the local populace. Utilizing a retrospective record review
      protocol, we examined 282 mental health files of soldiers assigned to a brigade
      combat team that operated from a large forward operating base in Iraq during the
      counterinsurgency campaign. Most reported sleep disturbance, depression, anxiety,
      irritability, and conflict with supervisors related to either operational stress,
      exposure to direct combat, or home front concerns. Most received brief individual
      supportive therapy or attended solution-focused group counseling emphasizing life
      skills training, post-traumatic stress treatment, women's support, or
      relationship skills. Psychopharmacologic treatment was an essential adjunct to
      the counseling program. Results indicate that supporting a COIN deployment
      requires a comprehensive mental health program that can respond to a wide range
      of mental health problems.

PMID- 22645875
TI  - Making mental health aerovac decisions in Afghanistan: a field report.
AB  - This article focuses on the clinical and administrative decision-making processes
      involved in medevacing psychiatric patients from Kandahar Airfield, Afghanistan,
      during major surge operations. This article highlights organizational realities
      pertaining to the medevac process and offers recommendations for incoming
      providers to optimize their effectiveness in managing at-risk patients in a
      combat zone.

PMID- 22645876
TI  - Impact on mental health of deploying as an individual augmentee in the U.K. Armed
      Forces.
AB  - Armed Forces personnel who deploy as individual augmentees (IAs), with a unit
      other than their formed unit, often fill shortages or provide specialized
      knowledge or skill sets. This article examined the effect of deploying as an IA
      on mental health outcomes and unit cohesion. A U.K. military cohort study was
      used to compare IAs (n = 1352) with personnel who had deployed with a formed unit
      (n = 2980). Differences between the groups in questionnaire assessed symptoms of
      post-traumatic stress disorder (PTSD Checklist-Civilian Version), common mental
      disorders (General Health Questionnaire-12) and alcohol misuse (Alcohol Use
      Disorders Identification Test) were examined with logistic and negative-binomial
      regression analyses. There was no difference between IAs and those who deployed
      with a formed unit in level of unit cohesion, symptoms of post-traumatic stress
      disorder or common mental disorder. Deployment as an IA was associated with less
      alcohol misuse (Odds Ratio 0.77, 95% Confidence Interval 0.63-0.94). IAs appeared
      able to integrate with the group they deployed with as levels of unit cohesion
      were similar to personnel who deployed with a formed unit. IAs were also at a
      lower risk of alcohol misuse compared to personnel who deployed with a formed
      unit.

PMID- 22645877
TI  - Psychological hardiness and coping style as risk/resilience factors for alcohol
      abuse.
AB  - Alcohol abuse is a growing problem in the military, and a costly one. The present
      study evaluates the potential role of psychological hardiness, an individual
      resilience resource, to stress-related problem drinking in a military population.
      We assess the association of psychological hardiness and avoidance coping style
      with alcohol use patterns in a large national sample of Norwegian military
      defense personnel. Results show that low hardiness and high avoidance coping are
      significant predictors of alcohol abuse. Also, the challenge facet of hardiness
      predicts risk of alcohol abuse among respondents with recent deployment
      experience, and this effect is greater for those with harsh deployment
      experiences. Older defense workers are also at higher risk, suggesting cumulative
      occupational stress may take a toll. This research indicates that hardiness and
      avoidance coping measures may serve as useful adjunct screening tools for alcohol
      abuse in the military.

PMID- 22645878
TI  - Postdeployment behavioral health screening: face-to-face versus virtual
      behavioral health interviews.
AB  - Virtual behavioral health (VBH) services are used frequently to address the high
      demand for behavioral health (BH) services in the military. Few studies have
      investigated the relationship between the use of VBH services and BH outcomes or
      preferences for the use of VBH technologies. In this article, we evaluated BH
      interviews conducted via video teleconferencing (VTC) or face-to-face in terms of
      BH symptoms, satisfaction rates, stigma, barriers to care, and preferences for
      future use of BH care. Soldiers (n = 307) from the headquarters element of an
      operational unit were surveyed 4 months following a 12-month deployment to Iraq.
      There were no significant differences in satisfaction rates based on interview
      modality, but significantly more soldiers preferred face-to-face interviews over
      VTC interviews in the future. Soldiers who preferred face-to-face interviews also
      reported higher levels of anxiety and depression symptoms than those who
      preferred VTC interviews. No significant age differences were found in terms of
      interview modality satisfaction or preference. Soldiers with greater deployment
      experience were more likely to report that they would not like using VTC if
      seeking BH care in the future than soldiers with less deployment experience.
      These findings highlight the importance of promoting choice in type of BH
      interview modality.

PMID- 22645879
TI  - Former combatants in Liberia: the burden of possible traumatic brain injury among
      demobilized combatants.
AB  - OBJECTIVE: To provide a better understanding of any associations between
      Disarmament, Demobilization, and Reintegration, previous head injury, and mental
      health symptoms among former combatants in Liberia. METHODS: A cluster-sampled
      national survey of the adult household-based Liberian population. FINDINGS:
      Former combatants with reported head injury were more likely to experience major
      depressive disorder symptoms, suicidal ideation and attempts, and current
      substance abuse. Former combatants with head injury are 2.83 times more likely to
      have major depressive disorder symptoms, and those with suspected traumatic brain
      injury are five times more likely to have post-traumatic stress disorder.
      INTERPRETATION: The poor mental health of former combatants in Liberia, both
      child and adult, might be mitigated if Disarmament, Demobilization, and
      Reintegration programming assessed participants for head trauma and traumatic
      brain injury using simple screening methods. The specific health and mental
      health needs of ex-combatants--a highly vulnerable group--will need to be
      addressed by Liberia. If left untreated, ex-combatants with high rates of
      suicidal ideation and post-traumatic stress disorder might be susceptible to re
      recruitment into new conflicts in the region.

PMID- 22645881
TI  - Evaluating the Joint Theater Trauma Registry as a data source to benchmark
      casualty care.
AB  - Just as data from civilian trauma registries have been used to benchmark and
      evaluate civilian trauma care, data contained within the Joint Theater Trauma
      Registry (JTTR) present a unique opportunity to benchmark combat care. Using the
      iterative steps of the benchmarking process, we evaluated data in the JTTR for
      suitability and established benchmarks for 24-hour mortality in casualties with
      polytrauma and a moderate or severe blunt traumatic brain injury (TBI). Mortality
      at 24 hours was greatest in those with polytrauma and a severe blunt TBI. No
      mortality was seen in casualties with polytrauma and a moderate blunt TBI.
      Secondary insults after TBI, especially hypothermia and hypoxemia, increased the
      odds of 24-hour mortality. Data contained in the JTTR were found to be suitable
      for establishing benchmarks. JTTR data may be useful in establishing benchmarks
      for other outcomes and types of combat injuries.

PMID- 22645880
TI  - Therapeutic alliance building during the child psychiatric intake: does VTC make
      a difference?
AB  - This study examined potential changes in perceptions of therapeutic ("working")
      alliance during a child's initial diagnostic interview from the parent's
      perspective. The major study objective was to determine whether parental
      perceptions of alliance vary by group (video teleconferencing [VTC], face-to-face
      [FTF]) over time (Pre, Post intake). It was predicted that parental alliance
      would be more favorable after an FTF encounter relative to a VTC intervention.
      Participants were recruited and enrolled in two study cohorts between August 2000
      and October 2005. Parents completed the Parental Perceptions of Alliance
      Questionnaire (PPAQ) immediately before (pre-PPAQ) and after (post-PPAQ) their
      interview. Analysis of variance (ANOVA) tests showed that the mean PPAQ scores of
      FTF groups being higher than that of VTC groups (controlling for time) was
      statistically significant, F (1,144) = 4.14, p = 0.04. However, upon further
      analysis, the interaction effect was not significant, F (1,144) = 1.20, p = 0.28.
      Findings from the current exploratory study suggest that, at least following an
      intake child psychiatric examination, parents' perceptions of therapeutic
      alliance are stronger than they were before intake for those conducted in an FTF
      format as well as through VTC.

PMID- 22645882
TI  - Physical training injuries and interventions for military recruits.
AB  - Low physical fitness levels are associated with increased musculoskeletal injury
      risk and attrition among military recruits. The authors review physical fitness
      trends, injury risk factors, and Department of the Army initiatives to address
      recruit fitness, injuries, and attrition. Initiatives include the Fitness
      Assessment Program, which reduced injury risk and attrition among low-fit
      trainees, and the Assessment of Recruit Motivation and Strength, which enabled
      the Army to enlist individuals exceeding body composition accession standards
      without increasing attrition. Physical Readiness Training (PRT) is the Army's
      primary initiative to address training-related injuries and attrition. PRT's
      inherent injury control and exercise progression components are designed to
      address low fitness levels across entry-level training. PRT has been shown to
      decrease injury rates, but low-fit recruits remain at increased risk regardless
      of program design. The authors recommend resuming pre-enlistment fitness
      screening and fitness programming before low-fit recruits begin entry-level
      training. The decision whether to screen for fitness before beginning entry-level
      training could be based upon the existing recruiting environment in terms of
      applicant supply and the demand for recruits. However, the Army should anticipate
      increased injury and attrition rates when discontinuing screening and/or fitness
      programming for low-fit recruits.

PMID- 22645883
TI  - Effects of different types of respiratory muscle training on exercise performance
      in runners.
AB  - To compare two different types of respiratory muscle training on exercise
      performance, a protocol was devised consisting of a combination of a 4-week, 12
      session resistive respiratory muscle training (RRMT) followed by a 4-week, 12
      session voluntary isocapnic hyperpnea training (VIHT) and conducted in
      experienced runners (4 men, 4 women). Measurements before and 5 days after
      training included: pulmonary function (spirometry), maximal inspiratory and
      expiratory mouth pressures, respiratory endurance time, maximal oxygen uptake
      (V(o2)max), running time to voluntary exhaustion at 80% V(o2)max, blood lactate
      concentration, and minute ventilation. There were no statistically significant
      differences in pulmonary functions and V(o2)max post-RRMT and post-VIHT compared
      to pre-RMT. Following RRMT the inspiratory muscle strength had improved by 23.8
      +/- 30% and 18.7 +/- 21.4% at rest and immediately after the running test,
      respectively. RRMT did not increase the time intense voluntary isocapnic
      ventilation could be maintained during rest while VIHT increased it (237 +/-
      207.8%). The duration of the endurance run was extended 17.7 +/- 6.5% after RRMT
      and 45.5 +/- 14.3% after VIHT.

PMID- 22645884
TI  - The effects of prophylactic ankle bracing on dynamic reach distance and obstacle
      course performance in military cadets.
AB  - Ankle braces can protect the ankle joint from ligament sprains and fractures
      during high-risk military activities such as physical training and parachuting.
      Although braces are recommended for injury prevention purposes, the impact of
      braces on physical performance is unknown. This study evaluated lace-up ankle
      braces, worn inside the boots, across three conditions: no brace, unilateral
      brace, and bilateral brace on the dependent variables of dynamic lower extremity
      reach and obstacle course performance. Thirty-seven military cadets were tested
      over 3 days. Ankle bracing had a small effect upon anterior and composite lower
      extremity reach distances. Bracing had no effect upon obstacle course performance
      times. Inside-the-boot ankle bracing restricts lower extremity reaching and
      mildly impacts mobility, however, no restrictions were observed with running,
      climbing, jumping, or negotiating obstacles. Lace-up ankle braces can be used in
      conjunction with combat boots to protect the ankle during high-risk activities
      without having an impact upon tactical movements.

PMID- 22645885
TI  - Effect of initial projectile speed on contamination distribution in a lower
      extremity surrogate "wound track".
AB  - This article presents an experimental study that examines the relationship
      between initial projectile speed and bacterial distribution along a wound track
      due to surface contamination. A ballistic gelatin cylinder was used as a lower
      extremity surrogate, and surface contamination was simulated using circular
      filter paper moistened with a solution containing Escherichia coli strain K-12
      that was previously transformed to express green fluorescent protein and be
      resistant to ampicillin. An 11.43-mm caliber round-nose lead projectile was shot
      through the contaminated area and into the extremity surrogate at firing
      velocities ranging from 61 to 199 m/s. The "wound track" was extracted and cut
      into 10 evenly spaced slices. Then, the permanent cavity was removed from each
      slice using a biopsy punch, liquefied, and grown on selective agar containing
      ampicillin. Direct and normalized bacterial colony counts and normalized extents
      of area covered by bacteria colonies were used to compare the differences between
      distribution trends corresponding to different projectile speeds. The results
      obtained showed that, for the cases considered, an increase in projectile speed
      resulted in a significant shift in the percentage of contamination from the
      "wound" entrance region to the "wound" exit region.

PMID- 22645886
TI  - The effect of simulated field storage conditions on the accuracy of rapid user
      friendly blood pathogen detection kits.
AB  - Being able to test for the presence of blood pathogens at forward locations could
      reduce morbidity and mortality in the field. Rapid, user-friendly blood typing
      kits for detecting Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV),
      and Hepatitis B Virus (HBV) were evaluated to determine their accuracy after
      storage at various temperatures/humidities. Rates of positive tests of control
      groups, experimental groups, and industry standards were compared (Fisher's exact
      chi2, p < or = 0.05). Compared to the control group, 2 of 10 HIV detection
      devices were adversely affected by exposure to high temperature/high humidity or
      high temperature/low humidity. With one exception, none of the environmentally
      exposed HCV or HBV detection devices exhibited significant differences compared
      to those stored under control conditions. For HIV, HCV, and HBV devices, there
      were differences compared to the industry standard. Collectively, this evaluation
      of pathogen detection kits revealed that diagnostic performance varies among
      products and storage conditions, and that the tested products cannot be
      considered to be approved for use to screen blood, plasma, cell, or tissue
      donors.

PMID- 22645887
TI  - Air Force Hearing Conservation Program data 1998-2008: a cross-sectional analysis
      of positive threshold shifts.
AB  - BACKGROUND: Noise-induced hearing loss is an area of concern for military
      personnel. The purpose of this study was to conduct an analysis of hearing loss
      in military and civilian personnel enrolled in the Air Force Hearing Conservation
      Program between January 1, 1998 and December 31, 2008. METHODS: The research
      employed a cross-sectional design. Data stored in the Defense Occupational and
      Environmental Health Readiness System-Data Repository was analyzed. RESULTS:
      Among military personnel, the logistic regression model demonstrated a protective
      effect for enlisted members (OR = 0.78, p < 0.0001) and women (OR = 0.63, p <
      0.0001) and an increased odds of having a positive threshold shift (PTS) with
      increasing age group (OR = 1.919, p < 0.001). Among civilians, the logistic
      regression model demonstrated a protective effect for women (OR = 0.52, p <
      0.0001) and increased odds of having a PTS with increasing age group (OR = 1.73,
      p < 0.001). When compared to military personnel, civilian personnel had increased
      risk for PTS (RR = 1.68, 95% CI = 1.67-1.69). CONCLUSIONS: Increasing age and
      being male were associated with higher PTS rates. PTS rates were higher in
      officers than in enlisted military members. When compared to military personnel,
      civilian personnel were found to have an increased risk for PTS.

PMID- 22645888
TI  - Estimated incidence of multiple sclerosis among United States Armed Forces
      personnel using the Defense Medical Surveillance System.
AB  - BACKGROUND: The comprehensive longitudinal medical records of the U.S. Armed
      Forces provide a valuable tool to study the epidemiology of multiple sclerosis
      (MS) in persons from a diverse demography. OBJECTIVE: This study's objectives
      were to estimate the frequencies, incidence rates (IRs), trends, and correlates
      of MS among active component U.S. military members from 2000 to 2009. METHODS: An
      International Classification of Diseases, 9th Revision, code algorithm was used
      to identify MS cases from the Defense Medical Surveillance System database. IRs
      were determined by dividing the number of cases of MS by the total person-time of
      the active component during each year. RESULTS: During the 10-year period, there
      were 1,827 incident cases of MS with an overall IR of 12.9 per 100,000 person
      years (p-yrs). Black non-Hispanics had a higher IR: (18.3 per 100,000 p-yrs) than
      White non-Hispanics (12.5 per 100,000 p-yrs). The incidence of MS by birth month
      and geographic home did not show a clear trend of seasonality or latitudinal
      gradient. CONCLUSIONS: This investigation is the first longitudinal study of MS
      incidence in U.S. Armed Forces personnel. The study demonstrates higher IRs than
      seen in other populations and reveals a novel pattern of MS incidence by race.

PMID- 22645889
TI  - Descriptive epidemiology of intraocular pressure and corneal hysteresis among
      U.S. veterans.
AB  - PURPOSE: Several reports have revealed a difference in various populations
      regarding the variability of intraocular pressure (IOP) and corneal hysteresis
      (CH). This retrospective study was created to determine a profile for U.S.
      Veterans in a large outpatient clinical setting. OVERVIEW AND METHODOLOGY: The
      objective was to evaluate a random cohort of patient records in this clinical
      setting to determine the mean and standard deviation (SD) of the following
      parameters: Goldmann-correlated IOP (IOPg), CH, waveform score, and central
      corneal thickness from the Reichert Ocular Response Analyzer. RESULTS: All
      patient records were reviewed by Veteran Health Affairs Eye clinical staff which
      resulted in data collected on 538 eyes. The mean IOP of this cohort for IOPg was
      17.39 (SD 10.08). The mean for CH was calculated at 9.61 (SD 3.04) with a
      waveform score mean of 5.66 (SD 2.18) and central corneal thickness for 207 eyes
      was a mean of 545.09 (SD 51.09) nm. CONCLUSION: From the results, IOPg appears to
      be significantly higher and CH significantly lower than other populations
      reported in the literature. This information provides an accurate baseline for
      the evaluation of the U.S. veteran population for future.

PMID- 22645890
TI  - Occult femoral neck fracture associated with vitamin D deficiency diagnosed by
      MRI: case report.
AB  - Hip fractures in the young are exceedingly rare and are usually seen in instances
      of high energy trauma or metabolically altered bone states. In this case report,
      we present an occult femoral neck fracture, diagnosed by magnetic resonance
      imaging, in an otherwise healthy, young, active duty male patient with an
      isolated vitamin D deficiency treated using cannulated percutaneous screws.

PMID- 22645891
TI  - Enhanced U.S. Army HIV diagnostic algorithm used to diagnose acute HIV infection
      in a deployed soldier.
AB  - Antibody screening alone may fail to detect human immunodeficiency virus (HIV) in
      recently infected individuals. By U.S. Army regulation, HIV-infected soldiers are
      not permitted to deploy to areas of conflict, including Iraq and Afghanistan. We
      report here the first case of acute HIV infection (AHI) in a soldier in a combat
      area of operation detected by an enhanced U.S. Army HIV testing algorithm and
      discuss features of the tests which aided in clinical diagnosis. We tested the
      sample from the AHI case with a third generation HIV-1/HIV-2 plus O enzyme
      immunoassay, HIV-1 Western Blot, and a qualitative HIV-1 ribonucleic acid
      molecular diagnostic assay. Risk factors for HIV acquisition were elicited in an
      epidemiologic interview. Evaluation of the blood sample for AHI indicated an
      inconclusive serologic profile and a reactive HIV-1 ribonucleic acid result. The
      main risk factor for acquisition reported was unprotected sexual intercourse with
      casual strangers in the U.S. while on leave during deployment. The clinical
      diagnosis of AHI in a combat area of operation is important. Diagnosis of HIV is
      key to preventing adverse effects to the infected soldier from deployment
      stressors of deployment and further transmission via parenteral or sexual
      exposures.

PMID- 22645892
TI  - The use of recombinant activated factor VII in a patient with penetrating chest
      trauma and ongoing pulmonary hemorrhage.
AB  - A case is described where recombinant activated factor VII was used to control
      pulmonary hemorrhage in a patient who had sustained a high-velocity gunshot wound
      to the chest, in the deployed medical setting, allowing onward transfer of the
      patient to the United Kingdom for further management.

PMID- 22645893
TI  - Septic subacromial bursitis caused by Mycobacterium kansasii in an
      immunocompromised host.
AB  - Mycobacterium kansasii is a common cause of pulmonary infection as a result of
      nontuberculous mycobacteria, but is less commonly described as a cause of an
      orthopedic infection. We present the first case of M. kansasii subacromial septic
      bursitis in an immunocompromised host. This case demonstrates the diagnostic and
      treatment challenges associated with orthopedic infections caused by M. kansasii.

PMID- 22645894
TI  - Health insurance reform: labor versus health perspectives.
AB  - The Ministry of Labor (MOL) has submitted to the Council of Ministers a social
      security reform plan. The Ministry of Public Health (MOPH) considers that health
      financing should be dealt with as part of a more comprehensive health reform plan
      that falls under its prerogatives. While a virulent political discussion is
      taking place, major stakeholders' inputs are very limited and civil society is
      totally put away from the whole policy making process. The role of the media is
      restricted to reproducing political disputes, without meaningful substantive
      debate. This paper discusses health insurance reform from labor market as well as
      public health perspectives, and aims at launching a serious public debate on this
      crucial issue that touches the life of every citizen.

PMID- 22645895
TI  - [Risk factors of pneumothorax and hemorrhage in lung biopsy: a single institution
      experience].
AB  - OBJECTIVES: CT-guided transthoracic lung biopsy is widely used in pulmonary
      lesions diagnosis. This technique rarely entails severe complications such as
      pneumothorax and pulmonary hemorrhage which call for adequate candidates
      screening. The aim of our study is to statistically assess risk factors related
      to these two main complications, and determine the best diagnostic workup.
      MATERIALS AND METHODS: This retrospective study includes 110 patients who
      underwent CT-guided transthoracic biopsy of a pulmonary lesion. Rates of
      pneumothorax and pulmonary hemorrhage, as well as their severity, were evaluated,
      and a correlation with factors related to patients, lesions and biopsy technique
      were statistically analyzed. RESULTS: Higher rates of complications are
      significantly found with multiple punctures (pneumothorax risk multiplied by
      7.4), longer intra-parenchymal needle tract (5 and 7% higher risk of pneumothorax
      and hemorrhage for every 1 mm increase in depth), and with smaller lesions (2 and
      5% lower risk respectively for pneumothorax and hemorrhage for every 1 cm
      increase in lesion size). The presence of an interposing rib is associated with a
      higher rate of hemorrhage. CONCLUSION: Transthoracic lung biopsy is a minimally
      invasive technique. However, the presence of associated risk factors must lead to
      consider another diagnostic method.

PMID- 22645896
TI  - [Parental smoking during early pregnancy and congenital heart defects].
AB  - OBJECTIVES: Analyze the possible role that can play parental smoking during early
      pregnancy on the occurrence of different types of congenital heart defects (CHD).
      MATERIALS AND METHODS: Over a period of 4.5 years (between January 1, 2006 and
      June 30, 2010), data on all children who had an echocardiography were collected
      and entered in the National Register of Paediatric and Congenital Heart Disease,
      Lebanese Society of Cardiology, Beirut. Patients were divided into two groups:
      group I without CHD, and group II with CHD. Variables recorded were: age of
      mother, place of residence, parental smoking, the type of CHD, the sex of the
      child and consanguinity of the parents. We used nonparametric tests for comparing
      the two populations. The p value was considered significant when inferior to
      0.05. RESULTS: Group I consisted of 2466 patients and group II of 793 patients.
      Only valvar pulmonary stenosis (VPS) was highly associated with mothers who
      smoked 20 cigarettes or more per day (p = 0.03). When the mother and father
      consumed at least 20 cigarettes per day, VPS and coarctation of the aorta were
      associated with a significant p-value (0.03 and 0.02 respectively). CONCLUSION:
      Parental smoking in early pregnancy can be considered a risk factor for valvar
      pulmonary stenosis and coarctation of the aorta. Cessation of smoking by the
      parents before pregnancy could reduce the risk of their occurrence.

PMID- 22645897
TI  - Incidence of piriformis tendon preservation on the dislocation rate of total hip
      replacement following the posterior approach: a series of 226 cases.
AB  - BACKGROUND: Dislocation is a feared complication following total hip replacement
      (THR). While repairing the piriformis tendon after THR reduces dislocation, we
      analyze in this study the effect of piriformis tendon preservation on reducing
      the dislocation rate. MATERIAL AND METHODS: 226 THRs were done following the
      usual posterior approach and by the same surgeon. All patients received the same
      prosthetic design. All cases were primary THR. After reaching the external
      rotators, the piriformis muscle was identified and dissected on its inferior
      border from the gemellus superior and elevated by a retractor. Further stages
      were performed in the usual manner. Patients were followed up for a mean of 3
      years. RESULTS: 226 THRs were done for 217 patients, 118 of whom were females and
      99 were males with a mean age of 62. Nine patients received bilateral THRs. 112
      procedures were performed on the right side and 114 on the left side. THR was
      performed in 70 cases following femoral neck fractures and in 156 cases due to
      osteoarthritis. No intraoperative or long-term complications were found while
      preserving the piriformis. Postoperative hip X-rays showed good positioning of
      both the femoral and acetabular components. No cases of dislocation were
      identified after a mean follow-up of 3 years. CONCLUSION: Preservation of the
      piriformis tendon during the postero-lateral approach in THR is a possible
      surgical technique that is easy to use and reproducible in both arthritic and
      traumatic conditions. It follows an anatomical intermuscular plan and permits
      full exposure of both the proximal femur and the acetabulum. Compared to the
      literature, preserving the piriformis tendon seems to be superior to repairing it
      in terms of dislocation of THR.

PMID- 22645898
TI  - Acquired and genetic risk factors for deep vein thrombosis of lower extremities
      among Lebanese patients.
AB  - AIM: Venous thrombosis results from the interaction of environmental and genetic
      risk factors. These factors vary according to the ethnic and geographic
      distribution of the populations. The aim of this study is to define the role of
      acquired and genetic risk factors for venous thrombosis of lower extremities
      among Lebanese patients assessed in a university hospital and to discuss them
      according to the international literature. MATERIAL AND METHODS: From January
      2005 to January 2010, 166 patients (72 males and 94 females) were diagnosed with
      lower extremity deep vein thrombosis. Mean age was 67 years (range: 25 to 96
      years). RESULTS: The most frequently reported acquired risk factors for venous
      thrombosis in this study were advanced age, obesity, history of venous
      thromboembolism, immobilization, surgery, varicose veins and malignancy.
      Screening for prothrombotic genetic abnormalities was requested in patients with
      conditions highly suggestive of hypercoagulation state such as young patients,
      patients with spontaneous, recurrent or extensive venous thrombosis, patients
      with family history, oral contraceptives, air travel and pregnancy. All the 45
      patients (27.1%) tested for thrombophilia were positive and were carriers for
      factors V-Leiden (17.4%), MTHFR C 677 T (16.8%), MTHFR A 1298 C (4.8%), II G
      20210 A (1.8%) and V H 1299 R (1.2%) mutation. Twelve patients (7.2%) had
      increased homocysteine level. CONCLUSION: Advanced age is the most common risk
      factor for venous thrombosis in these series. Thrombophilia is the second most
      frequently observed risk factor and is related to the high prevalence of factor V
      Leiden and MTHFR C 677 T mutation among the Lebanese population.

PMID- 22645899
TI  - Influence of the weight status on hip bone strength indices in a group of
      sedentary adolescent girls.
AB  - OBJECTIVE: The aim of this study was to compare femoral shaft and
      intertrochanteric geometry in overweight and normal weight adolescent girls.
      METHODS AND RESULTS: This study included 22 overweight (Body mass index (BMI) >
      25 kg/m2) adolescent girls (15.4 +/- 2.4 years old) and 20 maturation-matched
      (15.2 +/- 1.9 years old) controls (BMI < 25 kg/m2). Body composition and BMD were
      assessed by dual-energy X-ray absorptiometry (DXA). To evaluate bone geometry,
      DXA scans were analyzed at the femoral shaft and the intertrochanteric region by
      the Hip Structure Analysis (HSA) program. Cross-sectional area (CSA), an index of
      axial compression strength, section modulus (Z), an index of bending strength,
      cross-sectional moment of inertia (CSMI), cortical thickness (CT) and buckling
      ratio (BR) were measured from bone mass profiles. Lean mass, body weight, fat
      mass and BMI were higher in overweight girls compared to controls (p < 0.001).
      CSA, Z, CSMI and CT were higher in overweight girls compared to controls (p <
      0.05) at the two regions (femoral shaft and intertrochanteric). After adjustment
      for maturation index (years since menarche), CSA, Z, CSMI and CT of the
      intertrochanteric region and CSA of the femoral shaft were higher in overweight
      girls compared to controls (p < 0.05). After adjustment for either body weight,
      lean mass or BMI, using a one-way analysis of covariance (ANCOVA), there were no
      differences between the two groups (overweight and controls) regarding the HSA
      variables (CSA, CSMI, Z, CT and BR) at the femoral shaft and the
      intertrochanteric. CONCLUSION: This study suggests that overweight adolescent
      girls have greater indices of bone axial and bending strength in comparison to
      controls at the intertrochanteric after adjustment for maturation index.

PMID- 22645900
TI  - Medication prescribing errors: data from seven Lebanese hospitals.
AB  - INTRODUCTION: Medication prescribing errors are made all over the world. However,
      exact data about them are lacking in Lebanon. Our objective was to describe
      medication errors, including drug-drug interactions in medication orders given to
      patients admitted to Lebanese hospitals. METHODS: A prospective study was carried
      out on 313 patients taken from seven Lebanese hospitals; 1826 medication orders
      were assessed for errors and 456 drug-drug interactions were found. Data was
      entered and analyzed on SPSS. RESULTS: Around 40% of medication orders were
      judged to comprise at least one prescribing error, mainly no ordering of
      parameters monitoring (20%), unnecessary medication (9%), and no indication (7%).
      Errors occurred mainly in the pediatrics (50%) and internal medicine wards (40%).
      Having an infectious or gastrointestinal problem almost doubled the risk of
      medication prescribing error. Antiulcer agents, NSAIDs, antibiotics and steroidal
      agents were the medications mainly involved. Meanwhile, 12 adverse medication
      events were reported, with an odds ratio of association to a medication error of
      7.4 (p = 0.004). As for drug-drug interaction (DDI), prescriptions comprised zero
      to 29 interactions, involving medications with low margin of safety such as
      acenocoumarol, amiodarone and valproate. Pharmacodynamic interactions were mainly
      found (60%). The majority of DDI were of high clinical significance and well
      documented (80%), with moderate (59%) to major (17%) severity. CONCLUSION: These
      results highlight the urgency of an intervention to improve patients' outcomes
      and avoid deleterious impact of inadequate medication use in Lebanon. The
      presence of a clinical pharmacist, the inclusion of computerized systems and the
      application of drug management policies are suggested to decrease medication
      prescribing errors and enhance the physician attention to DDI.

PMID- 22645902
TI  - Osteomyelitis: review of pathophysiology, diagnostic modalities and therapeutic
      options.
AB  - Osteomyelitis can affect every bone and is heterogeneous in its pathophysiology
      and presentation. When the diagnosis is clinically suspected, further studies
      such as serum inflammatory markers and imaging studies should be performed.
      Magnetic resonance imaging can be very useful in establishing the diagnosis and
      determining the extent of infection. When possible, bone specimens should be
      obtained and cultured prior to the initiation of antimicrobial therapy. Surgical
      debridement is often required for chronic or contiguous osteomyelitis for
      successful eradication of the infection. The ultimate test-of-cure is the lack of
      clinical relapse after the discontinuation of antimicrobials.

PMID- 22645901
TI  - Use of herbal medications and their perceived effects among adults in the Greater
      Beirut area.
AB  - OBJECTIVES: To measure the magnitude of use of so-called "herbal medications"
      with or without prescribed drugs and to assess the benefits and adverse effects
      perceived by herbal users in the Greater Beirut area. METHODS: A sample survey of
      480 adults (18-65) in the Greater Beirut (GB) area was conducted over a one-month
      period in 2009. RESULTS: The estimated weighted prevalence of herbal use in the
      previous 12 months in GB was 58.9% (56.7-61.2). Most of the 293 users (72.4%)
      believed that their use had been of no benefit, but 70% thought use was
      relatively safe. Of users, 53% were concomitantly using conventional drugs for a
      chronic condition yet only 45% had thought of informing their physician about
      herbal use. Among the "concomitant users" 60% had suffered some form of adverse
      effects. CONCLUSIONS: There is a relatively high prevalence of herbal medicine
      use in Greater Beirut, with an important rate of self-reported adverse effects,
      especially among those who suffer chronic conditions, and little exchange of
      information on this between patients and doctors. Data indicate the need to
      educate patients about realities associated with abusive use, expected benefits
      and potential drug-herb interaction. Patients on chronic medications should not
      be left to actually experience adverse effects in order to discover that herbal
      medicines are not always effective or innocuous.

PMID- 22645903
TI  - [Medical teaching in the 19th century in the Middle East through one of the
      pioneers of Lebanese medicine ].

PMID- 22645904
TI  - A preliminary study of the dental implant therapy--initial osteogenesis of human
      mesenchymal stem (HMS0014) cells on titanium discs with different surface
      modifications.
AB  - HMS0014 cells were GBR-engineered to proliferate and differentiate into mature
      osteoblast(Ob)-like cells, which initiated hard tissue matrix deposition in both
      monolayer and PuraMatrix 3-D cultures. Subsequently, the osteogenesis initiated
      with attachment/adhesion of HMS0014 cells on either Titanium (Ti) or Ti alloy
      discs modified with osteoconductive/ osteoinductive surface textures/substrates
      (e.g., Disc-AO, Disc-HA, Disc-SPI) was histologically assessed. The results
      obtained were as follows: 1) The HMS0014 cells actively proliferated and
      differentiated into mature Obs to initiate mineralisation of the ECM since day 1
      in both monolayer and 3-D cultures; mineralization was prominently progressed
      between day 7 and day 14 of cultures. 2) The SEM of 60-minute(min)s specimens
      demonstrated a loose distribution of proliferating spherical-to-polygonal (10 to
      40 microm in diameter, avg.) cells with a bulging cell body sending out many
      minute filopodia and some lamellipodia to attach with the substrate in the
      concavities. 3) In the 180-min specimens, the cultured HMS0014 cells actively
      proliferated and spread into flat, large polygonal cells with prominent
      lamellipodia and dendritic filopodia (30 microm x 90 microm to 100 microm x 200
      microm, approx.) to employ cell-to-substrate and intercellular attachments. 4) On
      the other hand, the present immunohistochemistry of the attached HMS0014 cells
      demonstrated the co-expression of F-actin (actin filaments of the cytoskeleton)
      and CD51 (aV integrin) in both the 60-min and 180-min specimens. We concluded
      that the present GBR method enhanced HMS0014 cells to initiate an osteogenesis
      process with a direct bone-to-substratum contact on Ti discs which were subject
      to different surface modifications.

PMID- 22645905
TI  - Cell- and region-specific expression of sugar chains in the mouse epididymal
      epithelium using lectin histochemistry combined with immunohistochemistry.
AB  - To understand the cytochemical properties of epididymal epithelial cells, the
      characteristics of glycoconjugates in the mouse epididymis were examined using
      the technique of lectin histochemistry combined with immunohistochemistry.
      Characteristic staining patterns depending on the type of lectins were observed
      in the epididymal epithelium. Principal cells expressed N-acetyl-D-galactosamine
      (GalNAc), N-acetyl-D-glucosamine (GlcNAc), and Fucose in the proximal region of
      the epididymis and Mannose, Glucose, and Galactose in the distal region of the
      epididymis. Basal cells expressed Mannose, Glucose, Galactose, and GlcNAc in the
      proximal region and Galactose in the distal region. On the other hand, clear
      cells expressed various sugar residues and differences among regions were not
      observed. Interestingly, principal cells, clear cells, and basal cells
      specifically reacted with Ulex Europaeus-Agglutinin I (UEA-I lectin), Maackia
      Amurensis-Lectin I (MAL-I lectin), and Griffonia simplicifolia Lectin I-B4 (GS-I
      B lectin), respectively. These findings indicate that the selectivity in lectin
      reactivity for distinct cell types and segment-dependent staining in the
      epididymis may be related to cellular and regional differences in function.
      Furthermore, because some lectins stain particular cells or cellular compartments
      selectively, these lectins could be useful markers for histopathological
      evaluation of diseases or diagnosis of male infertility.

PMID- 22645906
TI  - Double inferior vena cava with interiliac vein: a case report and literature
      review.
AB  - The duplication of the inferior vena cava (IVC) is a rare, but well-recognized
      anomaly. Duplicated IVC has a significant relevance for retroperitoneal surgery
      and venous interventional radiology. We report a case of duplicated IVC, which
      was observed during routine dissection of an 84-year-old Japanese female cadaver.
      The interiliac vein between the duplicated IVC ran obliquely upwards from left to
      right. We performed systematic literature review of published reports based on
      Pubmed and Medline from 1967 to 2011. Of 109 cases with IVC anomalies identified
      by the literature search, 22 cases (20.2%) displayed no interiliac anastomosis.
      The interiliac vein connecting duplicated IVC existed in 74 cases (67.9%).
      According to the running direction of the interiliac vein, we found that the vein
      ran from left to right in 42 cases, coursed from right to left in 19 cases, and
      ran horizontally in 13 cases. Thirteen left IVC displayed symmetrical-to-normal
      connection with the bilateral common iliac veins. Awareness of these venous
      variations is necessary to reduce surgical risk and to determine strategy in
      interventional radiology.

PMID- 22645907
TI  - Changes in lectin-binding sites on epididymal cells during postnatal development
      of the mouse.
AB  - Using lectin histochemistry combined with immunohistochemistry, we recently
      demonstrated that the principal, clear, and basal cells in the adult mouse
      epididymis specifically react with UEA-I, MAL-I, and GS-IB lectins, respectively.
      The present study examined the distribution of the lectin-binding sites for some
      lectins on the epididymal epithelium during postnatal development. Galactose
      staining with GS-IB was first detected in some of the undifferentiated epithelial
      cells in mice aged 1 week, and this characteristic became specific to basal cells
      in mice aged 2 weeks and above. Fucose staining with UEA-I was first detected in
      the principal cells in mice aged 3 weeks. Staining of sialic acid with MAL-I was
      first detected in all undifferentiated epithelial cells in mice aged 1 week, and
      this characteristic became specific to the narrow and clear cells in all regions
      and to the principal cells in regions IV and V in mice aged 3 weeks. The results
      indicate that epididymal differentiation is characterized by the expression of
      cell- and region-specific sugar chains that appear early during postnatal
      development before the sperm arrives in the epididymis.

PMID- 22645909
TI  - [Quality of life in patients with coronary artery disease after stem cell
      therapy].
AB  - The main group included 17 patients with distal lesion of the coronary bed in
      whom the performance of complete direct myocardium revascularization was not
      possible. The autologous bone marrow mononuclears were administered to the main
      group patients at the period from 2008 to 2010. The control group consisted of 10
      patients given standard medicamentous therapy. A year later in the main group
      patients there was a decrease of median of the functional stenocardia class,
      median of metabolic units by the data of loading tests, median of the number of
      nitroglycerin pills for a week taken by the patients as compared with the control
      group. By the data of OECT and PECT a year later in the main group there was an
      improved perfusion in all the myocardium segments. In the control group on the
      contrary there was negative dynamics in all the indices in question.

PMID- 22645908
TI  - [Surgical treatment of chronic thrombo-embolic pulmonary hypertension with
      floating thrombi in the right heart ventricle].
AB  - A 31 years old male patient was admitted to a resuscitation unit with severe
      dyspnea (MMRC 4 grade). The patient had the dyspnea for 3 months.The diagnosis of
      chronic thrombo-embolic pulmonary hypertension with floating thrombi in the right
      heart ventricle was established. On the sixth day of admission after IVC filter
      insertion, the patient underwent thromboectomy with pulmonary endarterectomy. For
      an access to segmentary pulmonary arteries during operation SVC and the aorta had
      been cross-clamped. The duration of deep hypothermic (20 degrees C) circulatory
      arrest was 54 minutes. The patient was discharged in satisfactory condition on
      the 17th day. At the check-up at 3 months the dyspnea was absent and heart
      hemodynamic parameters had been normalized.

PMID- 22645910
TI  - [The value of intraoperative Doppler-flowmetry in assessment of blood flow after
      the hepatic artery reconstruction during the orthotopic liver transplantation].
AB  - The practical relevance of volumetric blood flow in the hepatic artery during
      orthotopic liver transplantation was determined. From May 2009 to January 2011 25
      patients underwent orthotopic liver transplantation. Volumetric blood flow in the
      hepatic artery is routinely measured using a Doppler flow meter during the
      operation. In 15 cases out of 25 (60%) the blood flow rate immediately after the
      formation of arterial anastomosis was 150 ml/min (190 +/- 40 ml/min) and
      increased to adequate with repeated measurements. In 2 cases out of 25 (8%) the
      blood flow rate reduced in repeated measurements, but by the end of operation the
      blood flow to the hepatic artery was at the satisfactory level. Blood flow less
      than 150ml/min immediately after the formation of arterial anastomosis was found
      in 8 cases out of 25 (32%). The cause of inadequate blood flow was identified and
      corrected. There were no cases of hepatic artery thrombosis at the early
      postoperative period. The routine use of intraoperative blood flow measurements
      allows timely determination of insufficient arterial blood supply of the
      transplant and elimination of its causes.

PMID- 22645911
TI  - [Roentgenoendovascular hemostasis of arterial bleeding after major surgery for
      pancreatic cancer].
AB  - The efficacy of angiographic hemostasis in cases of massive arterial bleeding
      after major pancreatic resection was evaluated. Late life-threatening arterial
      hemorrhage developed in 3 out of 65 patients (4.6%) within 12, 20 and 42 days
      after pancreatic carcinoma resection. In all cases emergency
      roentgenoendovascular procedures were fulfilled for hemostasis. Six therapeutic
      angiographic procedures (from one to three per a patient) were performed. All of
      them were clinically and technically successful. Depending on the bleeding
      localization and the character of vascular lesion, the embolization (n = 5) or
      stent-grafting (n = 1) were used. The further prognosis was dependent on the
      success of treatment of complications and the course of the malignant disease.
      The emergency angiography with endovascular hemostasis appears to be the method
      of choice in treatment of postoperative visceral bleedings especially in patients
      with high surgical risk.

PMID- 22645912
TI  - [Bleedings after surgery on the thyroid gland requiring reoperations].
AB  - The results of using improved methods of prophylactics of postoperative bleedings
      in operations on the thyroid gland are described. It was shown that a hypertonic
      test from 0.5 ml of 1.0% solution of Mezaton made before the end of operation as
      well a decrease of the volume of the ablated gland bed using an original fascio
      tracheopexy allowed reduction of frequency of bleedings in the thyroid gland bed
      from 0.36% per 2750 operations in 2005-2007 to 0.16% per 826 surgical procedures
      at the period 2008-2010. The symptoms of bleedings in the thyroid gland bed are
      enumerated and efficient actions of the personnel and surgeons for prevention of
      asphyxia and cardiac arrest.

PMID- 22645913
TI  - [Differential diagnostics of ovarial neoplasms and hydatids of pelvic
      localization in girls].
AB  - An analysis of differential diagnostics and results of treatment of hydatids in
      pelvis is described. For 36 year exploration and operations were fulfilled in 465
      patients with hydatids of different localization, in 6 (1.3%) of them there was
      pelvic localization. Cystic formations of the ovaries were found in 211 girls, in
      5 (2.4%) it was pelvic localization of hydatids. In 2 cases an isolated lesion of
      the small pelvis organs was noted, in 4 patients small pelvis hydatids were
      combined with lesions of other organs. The authors propose a scheme of
      differential diagnostics with neoplasms of the ovaries. All the patients
      underwent organ-saving operations. There were no relapses.

PMID- 22645915
TI  - [The application of antiadhesive means in prevention of peritoneal commissures].
AB  - The article presents our experience with using antiadhesive means "Seprafilm",
      "Interceed" and "Adept" in patients with abdominal adhesive disease. "Seprafilm"
      was applied in 18 patients, among them 13 underwent laparoscopic and 5 open
      adhesiolysis. Liquid antiadhesive barrier "Adept" was used in 53 patients (in 33-
      laparoscopically and in 20--by laparotomy). "Interceed" mesh was used in 16
      patients in open adhesiolysis. The combination of laparoscopy and antiadhesive
      barrier allows receiving good results by minimization of the operative trauma and
      influencing the process of adhesion formation. During laparoscopic interventions
      the application of liquid antiadhesive means is technically more convenient.

PMID- 22645914
TI  - [Diagnostics and surgical treatment of liver echinococcosis in Latvia].
AB  - The results of treatment of 44 patients (during the period 1996 - 2010) with
      liver echinococcosis (LE) were analysed. Echinococcosis hydatid (EH) cyst was
      found in 15 patients, alveolar echinococcosis (AE)--in 29 patients, 11.3% of
      cases were asymptomatical, different clinical symptoms were found in 36.4% of
      patients and 52.3% of patients were admited due to severe complications. Surgical
      treatment was performed in 41 patients. Among 15 patients with hydatid liver cyst
      3--underwent liver resection, 8--pericystechinococcectomy, 4--guided percutaneous
      treatment--PAIR. No complications or recurrences were noted. Radical operations
      were performed in 12 patients with AE (41.3%), 11 of them had asymptomatical or
      noncomplicated disease. Recurrence appeared in one patient (8.3%). Nonradical or
      palliative operations due to AE complications were performed in 15 patients
      (51.7%). Complication at the postoperative periods occurred in 17% of patients
      with AE and lethality rate came to 3.4%. The diagnosis made at the early
      asymptomatic state and the following selection of combination of surgical
      approach and medicamental treatment (albendazol) can improve the results of
      treatment of patients with liver echinococcosis.

PMID- 22645916
TI  - [Reconstructive-restorative operations by the method of invagination in
      colorectal surgery].
AB  - The authors made an analysis of results of surgical treatment of 41 patients who
      underwent reconstructive large bowel anastomosis by the Hartman procedure. In 19
      (46.3%) patients the anastomoses were performed by traditional methods (end-to
      end and end-to-side) using a two-row suture. In 22 (53.7) patients the
      anastomoses were made by one-row sutures. The authors conclude that the results
      of formation of invaginated colorectal anastomosis depend on the method of
      forming anastomosis, with the performing of colorectal anastomosis by traditional
      method fraught with the development of the content reflux in the outlet. The
      authors proposed a method of forming colorectal anastomoses by invagination using
      a one-row suture. The obtained function of the valve prevents regurgitation of
      the intestinal content and is considered to be a measure for preventing reflux.

PMID- 22645917
TI  - [Minimally invasive two-stage treatment of cholecystocholedocholithiasis].
AB  - Two groups of patients in whom two-stage treatment of
      cholecystocholedocholithiasis was performed with different succession of using
      endoscopic papillosphincterotomy (EPST) and laparoscopic cholecystectomy (LCE)
      were compared. In 59 patients (1st group) EPST was used as the first stage, in 67
      patients (2nd group) LCE and drainage of choledochus preceded the endoscopic
      intervention. The effectiveness of EPST was 93.3 and 95.5% correspondingly in the
      first and second groups. There were no considerable differences in the frequency
      of complications, period of treatment at the hospital in the two groups.
      Lythextraction was obtained considerably more often at the first attempt in the
      second group of patients (79.1% versus 59.9%, p < 0.05). Due to inefficiency of
      EPST in three cases in the second group of patients reoperations were required.
      Thus, EPST should be performed before LCE for the rationally planned further
      treatment in case of its inefficiency.

PMID- 22645918
TI  - [A case of successful surgical correction of posttraumatic aneurysm of the left
      ventricle].

PMID- 22645919
TI  - [Ileotyphlitis].

PMID- 22645920
TI  - [Successful surgical and roentgen-endovascular treatment of a patient with
      repeated vascular complications after transplantation of the liver].

PMID- 22645921
TI  - [Gas-gangrene of the liver as a manifestation of endogenous clostridial sepsis].

PMID- 22645922
TI  - [Prophylactics and treatment of peritoneal commissures].
AB  - The means for using prophylactic measures for prevention of the development of
      the adhesion process in the abdominal cavity are divided by the authors into two
      groups: for primary and secondary prophylactics. The mechanism of action of means
      for primary prophylactics is directed to restoration of the peritoneum
      mesothelium and its function; secondary prophylactics--to prevention of adhesions
      of scarry regenerated leaves of the parietal and visceral peritoneum. The
      findings are analyzed. The authors give recommendations for using means against
      adhesions. The necessity to choose the means for prophylactics depending on the
      state of the abdominal cavity is grounded (first operation or reoperation,
      planned or emergency operation). On the basis of the personal experience the
      authors recommend measures of the primary and secondary prophylactics of the
      adhesion process.

PMID- 22645923
TI  - [Investigation of the method of electric welding of organs and tissues on the
      models of clinical operations in experiment].
AB  - A new method of sutureless connection of tissues during surgical procedures was
      developed. Potentialities of the method of electric welding of biological tissues
      in abdominal surgery are studied. For this purpose an investigation of
      regeneration processes in the area of using electric welding on the large
      intestine as well as the liver under conditions of intact tissues and against the
      background of hyperglycemia and atherosclerosis model was performed.

PMID- 22645924
TI  - [Monitoring of preliminary medico-economical standards for management of the
      quality of the advanced technology onconeuro-surgical care].

PMID- 22645925
TI  - [Pathogenesis of the formation and results of surgical treatment of intestinal
      fistulas in patients with pancreatonecrosis].

PMID- 22645926
TI  - ["Severe complications of nematodoses"].

PMID- 22645927
TI  - [Combined operative interventions in lung cancer with involvement of the major
      vessels and atrium].

PMID- 22645929
TI  - [Behcet's disease: no longer blinding].

PMID- 22645928
TI  - [Autodermoplasty as an alternative to alloplastic prosthesis of the anterior
      abdominal wall].

PMID- 22645930
TI  - [Effects of laser in situ keratomileusis on intraocular pressure measurements in
      Japanese myopic eyes].
AB  - PURPOSE: To prospectively compare preoperative and postoperative measurements of
      intraocular pressure (IOP) using Goldmann applanation tonometry (GAT), noncontact
      tonometer (NCT), and Dynamic contour tonometer (DCT) in eyes undergoing myopic
      laser in situ keratomileusis (LASIK) and to examine the effects of preoperative
      corneal curvature and IOP, and the change in central corneal thickness (CCT).
      METHODS: One hundred six eyes of 53 patients underwent myopic LASIK with -5.3 +/-
      2.3 (mean +/- SD) diopters. Within 4 weeks before and at 1 month after LASIK, IOP
      using GAT, NCT and DCT and CCT were measured. RESULTS: Postoperatively, although
      IOP was reduced in the three measurements, IOP changes in DCT (-0.9 +/- 1.7 mmHg)
      were significantly lower than in the GAT (-3.6 +/- 2.1 mmHg) and in the NCT (-4.7
      +/- 1.9 mmHg) measurements (p < 0.001, Tukey test). In all the measurements, the
      decrease in the IOP increased with the higher preoperative IOP (p < 0.001).
      Changes in the CCT were significantly correlated in the GAT and NCT measurements
      (p < 0.015). CONCLUSIONS: IOP measurements using DCT minimized the changes in IOP
      readings after myopic LASIK in Japanese eye. This demonstrated that the DCT was
      effective for IOP monitoring after LASIK.

PMID- 22645931
TI  - [Indications and surgical outcomes of amniotic membrane transplantation].
AB  - PURPOSE: To evaluate the indications and surgical outcomes of amniotic membrane
      transplantation (AMT) for ocular-surface disease. SUBJECTS AND METHODS: This
      study involved 304 AMTs performed at Kyoto Prefectural University of Medicine
      between April 1998 and March 2008. Preoperative diagnoses, clinical features,
      surgical procedures and postoperative outcomes were analyzed retrospectively.
      RESULTS: Of 304 cases, 145 cases had a pterygium (48 primary, 82 recurrent, and
      15 pseudo-pterygium). The recurrence rate at one year was 6.1% among the 99 cases
      of pterygium followed for at least one year postoperatively. Ninety-three cases
      had severe ocular surface diseases including ocular pemphigoid (30), chemical or
      thermal burn (29), Stevens-Johnson syndrome (23), and others (11) AMT and
      epithelial transplantation was combined in 64 cases, and successful ocular
      surface reconstruction was obtained in 88 cases (94.6%). Neoplasia was observed
      in 22 cases (12 benign, 10 malignant). The ocular-surface was successfully
      reconstructed in all cases by AMT combined with complete tumor resection. Other
      preoperative diagnoses included persistent epithelial defects (PED) (15),
      conjunctival chalasis (12) and uncontrollable glaucoma (11). No cases experienced
      any AMT-related complication. CONCLUSIONS: AMT proved effective for preventing
      the recurrence of pterygium and for ocular-surface reconstruction in patients
      with severe ocular-surface disease or ocular-surface neoplasia.

PMID- 22645932
TI  - [Relationship between the extent of subarachnoid hemorrhage and intraocular
      hemorrhages in patients with subarachnoid hemorrhage].
AB  - PURPOSE: To examine the relationship between the extent of subarachnoid
      hemorrhage and intraocular hemorrhages in patients with subarachnoid hemorrhage.
      SUBJECTS AND METHOD: A total, of 63 patients (25 men and 38 women, mean age 58
      years). The subarachnoid hemorrhage quantity was graded according to the Fisher
      scale and compared with hemorrhages in the ocular fundus. RESULTS: Either
      vitreous or preretinal hemorrhages in either one or both eyes (vitreous
      hemorrhages) were present in 16 patients (25%). Retinal hemorrhages in either one
      or both eyes (retinal hemorrhages) were present in 12 patients (19%). Intraocular
      hemorrhage was absent in the other 35 patients (56%). The incidence of vitreous
      hemorrhage tended to be higher than the incidence of retinal hemorrhage or of the
      absence of hemorrhage as the rate of subarachnoid hemorrhage increased (Kruskal
      Wallis, p < 0.05). There was no significant correlation between retinal
      hemorrhages and the absence of hemorrhage in the Fisher grade IV chi2, p > 0.05).
      CONCLUSION: The onset of vitreous hemorrhage appears to be related to the extent
      of subarachnoid hemorrhage but the onset of retinal hemorrhage is not.

PMID- 22645933
TI  - [Comparison of central visual field visualization while using a combination of
      spherical intraocular lenses with vitreous contact lenses].
AB  - OBJECTIVE: To investigate intraocular lens (IOL) and vitreous contact lens (VCL)
      combinations that provide good central visual field visualization in vitreous
      surgery. METHOD: ZEMAX optical design software was used to perform optical
      simulations using the ray tracing method on a Gullstrand eye model. The implanted
      IOL was assumed to consist of material with a refractive index of 1.550 (high
      refractive index acrylic IOL), 1.470 (low refractive index acrylic IOL) and 1.413
      (silicon IOL), and was set as a biconvex spherical lens (optical diameter 6 mm,
      23.5 D). The VCL was assumed to have a refractive index of 1.900 (HEMA VCL),
      1.490 (PMMA VCL) and 1.413 (silicon VCL), and was set as a concave lens (optical
      diameter 10 mm) with a flat anterior surface and a posterior surface with a
      radius of curvature of 7.70 mm. The spherical aberration of the overall optical
      system, including the IOL-implanted eyeball and the VCL, was calculated. RESULTS:
      Spherical aberration was lowest with the silicon VCL for the high refractive
      index acrylic IOL and with the PMMA VCL for the low refractive index acrylic and
      silicon IOLs. CONCLUSION: The combinations providing the best central visual
      field visualization in vitreous surgery are a silicon VCL for implantation of a
      high refractive index acrylic IOL and a PMMA VCL for implantation of a low
      refractive index acrylic or silicon IOL.

PMID- 22645934
TI  - [Guidelines for glaucoma tube-shunt surgery].

PMID- 22645935
TI  - [Guidelines for the clinical management of ocular Behcet's disease ].

PMID- 22645936
TI  - [A review 50. Recent progress in corneal transplantation].

PMID- 22645937
TI  - [Health care delivery system in Japan: features, challenges and perspectives].

PMID- 22645938
TI  - Alzheimer's disease: diagnosis by different methods of voxel-based morphometry.
AB  - PURPOSE: The purpose of this study was to determine the optimal computational
      options in voxel-based morphometry (VBM) for discrimination between Alzheimer's
      disease (AD) patients and healthy control (HC) subjects. MATERIALS AND METHODS:
      Structural magnetic resonance images of 24 AD patients and 26 HC subjects were
      analyzed using VBM to determine brain regions with significant gray matter (GM)
      loss due to AD. The VBM analyses were performed with 4 different computational
      options: gray matter concentration (GMC) analysis with and without global
      normalization, and gray matter volume (GMV) analysis, with and without global
      normalization. Statistical maps calculated with the 4 computational options were
      obtained at 3 different P-value thresholds (P < 0.001, P < 0.0005, and P <
      0.0001, uncorrected for multiple comparisons), yielding a total of 12 sets of
      maps, from which regions-of-interest (ROI) were generated for subsequent analyses
      of performance in terms of discrimination between AD patients and HC subjects as
      based on the mean value of either the GMC or GMV within the ROI for each of the
      12 maps. Discrimination performance was evaluated by means of comparing the area
      under-the-curve derived from the receiver-operating characteristic analysis as
      well as on the accuracy of the discrimination. RESULTS: Discrimination based on
      GMC analysis resulted in better performance than that based on GMV analysis. The
      best discrimination performance was achieved with GMC analysis either with or
      without proportional global normalization. CONCLUSION: The findings suggested
      that GMC-based VBM is better suited than GMV-based VBM for discrimination between
      AD patients and HC subjects.

PMID- 22645939
TI  - [Role of receptor transactivation in the cardioprotective effects of
      preconditioning and postconditioning].
AB  - Analysis of published data indicates that the activity of receptors for
      adenosine, opioids, bradykinin, calcitonin-gene related peptides (CGRP) and
      epidermal growth factor (EGF) play important role in triggering the
      cardioprotective effects of ischemic preconditioning. Cannabinoids mimic the
      infarct-sparing effects of preconditioning. Endogenous adenosine, opioids,
      bradykinin and CGRP have also been implicated in infarct-reduction with ischemic
      postconditioning. Again, cannabinoids also mimic the protective effect of
      postconditioning. Recent works support heterodimerization of G-protein coupled
      receptors (GPCRs), and GPCR transactivation of EGF receptors. It was found that
      cross-talk between delta(j)-opioid receptors and adenosine A(1)-receptors is
      essential to cardiac protection. Furthermore, evidence implicates EGF receptor
      transactivation in cardioprotective effect of multiple GPCrs including adenosine,
      acetylcholine, bradykinin, and opioid receptors. Such findings support a
      convergent pathway in which multiple GPCRs may interact (or function
      independently) to transactivate EGF receptor-dependent kinase signaling and
      cytoprotection.

PMID- 22645940
TI  - [Influence of D2-receptor blockade on the nitrergic system activity of the
      nucleus accumbens].
AB  - In Sprague-Dawley rats, by means of in vivo microdialysis combined with HPLC
      analysis it was shown that the infusion into the n. accumbens of the D2-receptor
      antagonist raclopride (20, 100 microM) did not affect extracellular level
      ofcitrulline (an NO co-product) in this brain area. The intraaccumbal infusion of
      NMDA, an NMDA receptor agonist (100 microM) caused a rise of the extracellular
      citrulline level in this brain area. This rise was prevented by intraaccumbal
      infusion of 0.5 mM 7-nitroindazole, a neuronal NO-synthase inhibitor, and it was
      significantly reduced by the infusion of raclopride (20, 100 microM) into this
      brain area. The data obtained suggest that the D2-receptors of the n. accumbens
      are implicated in the regulation of neuronal NO-synthase activity induced by
      local NMDA receptor stimulation.

PMID- 22645941
TI  - [Peripheral acting mediators pain and analgesia potentiate the central analgesic
      action of fentanyl and dipyrone].
AB  - Intramuscular (i.m.) administration of the central analgesics fentanyl and
      dipyrone, and also mediators of pain such as L-glutamate, CCK, ATP, phenylephine
      and analgesic mediator adenosine, slightly penetrating in CNS, in the minimum
      effective dose (MED) cause the maximal analgesic effect in the tail flick test in
      rats. MED of dipyrone and fentanyl are decreased 50-220-fold after combined i.m.
      administration of each analgesic with L-glutamate, CCK, adenosine, ATP and
      phenylephrine in threshold, independently noneffective doses. The intragastric
      administration of lidocaine and also subdiaphragmatic vagotomy completely
      eliminate analgesic effects of the above mentioned combinations. CONCLUSION: the
      peripherically acting mediators of pain and analgesia after systemic
      administration potentiate central analgesic action of fentanyl and dipyrone as a
      result of the stimulation of vagal afferents of gastric mucosa.

PMID- 22645942
TI  - [Transgenerational consequences of acute antenatal stress in pregnant rats].
AB  - The aim of the present study was to investigate the effects of acute hypobaric
      hypoxia in early organogenesis on three following generations including pregnant
      females (FO) and two generations of their posterity (F1 and F2). Animals of all
      generations mentioned above demonstrated marked changes in motor and exploratory
      activity as well as in anxiety level while the litter of F1 and F2 generations
      showed also changes in learning ability. Besides, acute hypobaric hypoxia
      interfered in maternal behavior of females of the FO and F1 generations. The
      revealed changes kept till pubertal period. Possible mechanisms of gestational
      stress influence are discussed.

PMID- 22645943
TI  - [The pulmonary hemodynamics changes under experimental myocardial ischemia in
      rabbits following increased arterial pressure].
AB  - In acute experiments in anesthetized rabbits, changes of the pulmonary
      hemodynamics following myocardial ischemia in the region of the descendent left
      coronary artery were studied in control animals and after the infusion of
      adrenaline and phenylephrine. The pulmonary artery pressure was increased
      following infusion of these drugs; however, it decreased to normal level in the
      condition of myocardial ischemia. Meanwhile the pulmonary vascular resistance was
      elevated to the same level in both cases. Following adrenaline infusion, the
      pulmonary artery blood flow and venous return increased and, in the condition of
      myocardial ischemia, they decreased to normal level, but the left atrial pressure
      was decreased. Following phenylephrine infusion, the pulmonary artery blood flow
      and venous return did not change and, in the condition of myocardial ischemia,
      these parameters decreased lower than normal level but the left atrial pressure
      was elevated. Thus we concluded that equal values of the pulmonary artery
      pressure in both cases were caused by changes of different character in the left
      atrial pressure. The differences of the changes character and values of the
      pulmonary artery flow under experimental myocardial ischemia following the
      infusion of adrenaline and phenylephrine were caused by different shifts of the
      venous return.

PMID- 22645944
TI  - [The effect of noradrenaline on the neurogenic vasoreactivity at various
      frequencies of the electrical field stimulation].
AB  - The effect of 0.03-10.0 microM noradrenaline on the response to electrical field
      stimulation (EFS) of the juvenile rat tail artery segment was studied. At
      frequencies of the EFS equal to 10 or 40 Hz, noradrenaline was shown to cause
      much more pronounced potentiation or--at higher concentration--much less
      pronounced inhibition of the EFS-evoked constriction in arteries characterized by
      spontaneous decrease in the constriction value in the course of experiments as
      compared with arteries which were not characterized by such a decrease. At
      frequencies of the EFS equal to 3 or 5 Hz, the value and/or direction of the
      change in the neurogenic vasoconstriction in the presence of noradrenaline
      depends on the presence of the spontaneous decrease in the constriction evoked by
      EFS at 10 Hz, rather than at 3 or 5 Hz. It is concluded that the character of the
      change in the neurogenic vasoreactivity is a factor of a great importance for the
      prediction of the further change in the reactivity in the presence of
      noradrenaline.

PMID- 22645945
TI  - [Diet and water-salt balance in rats].
AB  - We compared parameters of water-salt balance in Wistar female rats fed normal
      chows during more than 2 weeks. Potassium content was 1.4-fold higher in diet I
      than in diet II, and sodium end water content was 3.3- and 7.5-fold higher in
      diet II than in diet I. Blood osmolality and concentration of Na+, K+, Mg2+ were
      equal in rats fed different chow. In water-loaded rats (5 ml of water/100 bw per
      os) fed different chow, urine flow rate did not differ, but solute-free water
      excretion was higher by 40.2% in the rats fed diet II vs. diet I. The sort of
      diet did not affect the renal sodium excretion during oral administration of 5 ml
      0.9% NaCl per 100 g bw to rats. After vasopressin injection solute-free water
      reabsorption was 1.5-fold higher in rats fed diet II. Natriuretic and hydruretic
      effect of exenatide, glucagon-like peptide 1 mimetic, was weaker in rats fed diet
      I. The data obtained indicate that organism can effectively maintain blood
      parameters. The modulation of hormone regulatory effects on water and sodium
      balance was found to depend on the state of organism under diet consumed
      continuously.

PMID- 22645946
TI  - [Expression of the genes Egf and Egfr in renal tissue of the hypertensive rats of
      the ISIAH strain].
AB  - Activation of the epidermal growth factor receptors (EGFR) plays an important
      role in the regulation of the kidney blood circulation and ion transport. The
      mRNA content of the epidermal growth factor (Egf) and its receptor (Egfr) genes
      were studied in the cortical and medullar parts of the kidney of rats with stress
      sensitive arterial hypertension (ISIAH strain) and normotensive WAG rats. There
      were no differences in the Egf expression between the rat strains at rest and
      under emotional stress in both the cortical and medullary kidney zones. As for
      Egfr transcription, it was significantly higher in the cortical and medullary
      parts of the ISIAH kidneys at rest as compared to the control WAG. Emotional
      stress induced no significant changes in the Egfr transcription in the cortical
      kidney parts of both rat strains. But prominent enhancement of Egfr transcription
      after emotional stress was observed in the kidney medulla of the WAG rats: it
      became the same as in the ISIAH rats at rest. It was suggested that the stress
      hormones might be involved in the regulation of Egfr transcription, and this
      connection between stress and Egfr gene activity might play a significant role in
      the kidney involvement in pathogenesis of stress sensitive arterial hypertension.

PMID- 22645947
TI  - [Characterization of depression-like behavior in prenatally stressed female rats
      during ovary cycle].
AB  - The aim of the present work was a comparative analysis of dynamics of depression
      like behavior in prenatally stressed and non-prenatally stressed female rats in
      the key phases of the ovary cycle. It was found that non-stressed female rats
      demonstrated high level of depression-like behavior in proestrous phase as
      compared to the diestrous phase, whereas these rats showed low level of
      depression-like behavior in estrous phase in Porsolt's test. On the contrary,
      there were no significant differences in extent of depression-like behavior
      between prenatally stressed rats in the diestrous and proestrous, although in the
      phase of estrous in these animals an increase in level of depression-like
      behavior was noted. Thus, the results of this study indicated pronounced effects
      of prenatal stress on the character of depression-like behavior of females in
      different phases of ovary cycle. This study revealed leveling and reversed action
      of prenatal stress on depression-like behavior in key phases of sexual cycle in
      female rats.

PMID- 22645948
TI  - [Effect of nitric oxide on 1 ml: peritoneal macrophages activity in normal
      pregnancy in white rats].
AB  - The activity of peritoneal macrophages, nitrotyrosine concentration and condition
      of free radical processes in normal pregnancy in white rats against the
      background of the introduction of donator (sodium nitrite) and inhibitor (Nw
      nitro-L-arginine methyl ester) of nitric oxide was studied. During normal
      pregnancy in animals, nitrotyrosine concentration, the activity of free radical
      processes, and phagocytosis increase. With the introduction of nitric oxide
      donator, NO level increases and after the injection of antagonist of nitric oxide
      it is reduced. These changes are accompanied by increased lipid peroxidation and
      activation of phagocytic activity of macrophages.

PMID- 22645949
TI  - [Mechanisms of human osteopenia and some peculiarities of bone metabolism in
      weightlessness conditions].
AB  - Systematically results and new analysis data on the investigation of human bone
      system in space flight, the orbital station Mir and International Space Station,
      are presented. The bone mineral density, bone mineral content, identified as bone
      mass and body composition using dual energy X-ray absorptiometry were measured.
      Theoretically, an expected bone mass loss in trabecular tissue of lower skeletal
      half may by described as a quickly developing but reversible osteopenia and
      considered as evidence of functional adaptation of bone tissue to the changing
      mechanical load. A hypothesis of main mechanisms of osteopenia in microgravity is
      presented. High individual variability of bone mass losses and stability of
      individual pattern of correlation between bone mass losses in different skeletal
      segments were found. It is not possible to identify the relationship between bone
      mass losses and duration of space missions. Therefore it is not a sufficient
      ground to calculate the probability of reaching the critical level of bone
      demineralization by prolonged space flight. The same relates to the probability
      of prognosis of bone quality changes. There is data about dual energy X-ray
      absorptiometry that is insufficient for this prognosis. The main direction of
      investigations is presented which might optimize the interplanetary mission from
      the point of view of skeletal mechanical functions preservation.

PMID- 22645950
TI  - [Infradian rhythmics of markers of physiologic and metabolic processes in Wistar
      male rats].
AB  - This work presents the results of the amplitude-phase structure of the
      physiological rhythms (locomotor activity) and steroid hormones production
      (common testosterone and cortisole) in gelded and intact Wistar male rats as well
      as rats exposed to an information load. The markers have been shown to depend on
      the social state of the animal. It was proved that there was a phase coincidence
      of the periods of the biological rhythms of common testosterone (intact rats),
      cortisole and locomotor activity for animals with different individualand
      typological features. It was shown that the oscillation period of infradian
      rhythms of the measured markers of physiologic and metabolic processes in the
      animals of all groups amounted to 4 days. It was found that infradian rhythms
      were not sensitive to factors of various genesis.

PMID- 22645951
TI  - [The effect of psychoemotional state on Lewis lung carcinoma metastasis].
AB  - The effect of a depression-like status formed by chronic stress on development of
      Lewis lung carcinoma metastases in C57Bl/6J mice was investigated. Two types of
      acute stress (restraint and social stress) were used for comparison. The
      depression-like status was induced by eight-week exposure to repeated but
      unpredictable stressors (chronic mild stress model) and was assessed in the
      forced swim test. Tumor cells were inoculated an hour after the onset of social
      stressor or immediately after physical or chronic stressor impacts. The number of
      metastases was counted 17 days after the inoculation. The results indicate that
      chronic mild stress provokes the development of a depression-like state in mice
      and causes a twofold increase in the number of metastases in the lungs, while
      both types of acute stress have no such effects. Thus, a depression-like
      psychoemotional status of animals enhances the metastasis of Lewis lung
      carcinoma.

PMID- 22645952
TI  - [Dependence of haemostasis system response from initial blood coagulation
      activity under total joints replacement].
AB  - Effect of the initial state of the plasma hemostasis on the hemocoagulation
      changes after the total arthroplasty surgery was studied in 100 patients with
      osteoarthritis. Indicators of coagulation, fibrinolysis, and physiological
      anticoagulants were determined before and after completion of the surgery, at
      days 1, 3, 7, and 13-14 postoperatively. Increased coagulation activity befor
      surgery enhanced blood clotting within three days after the surgery. Enhanced
      consumption of physiological anticoagulants reduced the ability to recover their
      level a week after arthroplasty. The raised activity of the fibrinolysis
      inhibitor retained the effect during three postoperative days. Initial
      abnormalities in plasma hemostasis enhance blood coagulation dysfunction caused
      by surgical intervention on the large joints.

PMID- 22645953
TI  - [The use of biological cardiac valve prostheses in modern cardiosurgery].
AB  - The present review is devoted to the problem of bioprosthetics of cardiac valves
      with special reference to its methodological and technological aspects including
      peculiarities of the most extensively used varieties of biological prostheses,
      current tends in the choice of indications for their application in the treatment
      of various congenital valvular diseases and for their implantation to the
      specific groups of patients. The main causes and mechanisms underlying structural
      degradation of bioprostheses depending on the technological processes of their
      manufacture and the patterns of calcium salt accumulation in the fixed tissues
      are considered Physiological consequences and delayed results of bioprosthetics
      are discussed.

PMID- 22645954
TI  - [The prospects for the use of chronomodulated chemo- and radiotherapy in
      oncology].
AB  - We have analysed the available worlds scientific literature concerning
      chronotherapy of malignant neoplasms of different localization. The review is
      focused on the results of multicenter investigations into this problem organized
      by the chronotherapy group in the framework of EORTC that have demonstrated a
      higher antiblastoma activity and improved tolerability of preparations applied in
      the chronomodulated regimen in comparison with the traditional treatment. Our
      original observations and recommendations ensuing from our many-year experience
      with the use of chemo- and radiotherapy of rectal and cervical cancer in the
      optimal time of day for the normal tissues constitute a basis for the more
      extensive introduction of chronobiological techniques to clinical practice.

PMID- 22645955
TI  - [The state of the digestive system in psoriasis].
AB  - Many authors emphasize the close relationship between skin lesions and digestive
      disorders in the patients suffering from psoriasis. The present literature review
      is focused on the results of investigations carried out in the recent years. The
      most detailed information concerns lesions in the stomach, small and large
      intestines, pancreas, and hepatobiliary system of psoriatic patients. The data
      obtained indicate that the treatment of skin pathology associated with psoriasis
      should be prescribed with due regard for the state of the digestive system.

PMID- 22645956
TI  - [Current views of etiopathogenetic mechanisms underlying the development of
      chronic pyelonephritis in subjects of different age].
AB  - A literature review of the issues pertinent to etiology and pathogenesis of
      chronic pyelonephritis is presented. Different aspects of pathogenesis of the
      disease in selected age groups of the patients (from childhood to senility) are
      considered and analysed with special reference to the etiology of acute and
      chronic pyelonephritis as well as the risk factors of this disease.

PMID- 22645957
TI  - [Cytomorphological analysis of remodeling of the bronchial wall in different
      types of bronchial asthma].
AB  - The objective of the present work was to search for the tissue and cellular
      markers of remodeling of bronchial mucosa in the patients with different clinical
      forms of bronchial asthma (BA). The use of up-to-date morphometric techniques has
      demonstrated that mild and moderately severe forms of bronchial asthma are
      accompanied by the development of Th2-immune response associated with increased
      production of interleukin-4 and marked degranulation of eosinophilic granulocytes
      resulting in desquamation of epithelium and goblet cell hyperplasia. The severe
      BA phenotype of "chronic asthma with fixed obstruction" is associated with the
      development of non-atopic inflammation in the bronchial mucous membrane that
      manifests itself as the increased concentration of interleukin-8 in bronchial
      mucosa and its neutrophilic infiltration leading to the development of pronounced
      subepithelial fibrosis, thickening of the basal membrane, and atrophy of
      epithelium. Specific structural changes in bronchial mucosa of the patients
      presenting with BA underlie functional disturbances that cause severe bronchial
      obstructive syndrome.

PMID- 22645958
TI  - [Obstructive sleep apnea syndrome, arterial hypertension, and obesity: clinical
      and functional aspects].
AB  - A total of 196 patients with increased body mass index (BMI) were included in the
      study designed to elucidate specific features of arterial hypertension (AH) and
      obstructive sleep apnea syndrome (OSAS). 65 of them did not experience OSAS
      episodes. All the patients were examined using 24-hour ECG and respiration
      monitoring combined with veloergometry (VEM). It was shown that OSAS alone in the
      absence of AH was associated with a 1.17-fold decrease of the physical load
      threshold compared with the respective control values. In the patients suffering
      AH and having high BMI, this parameter further decreased (by 1.22 and 1.35 times,
      respectively). In addition, they experienced changes in the period of recovery
      from veloergometry when their heart rate decreased but insignificantly by the end
      of the first minute after the termination of exercises. It is concluded that OSAS
      and AH influence tolerability, of physical exercises especially in the patients
      with elevated BMI.

PMID- 22645959
TI  - [Melatonin as a marker of intensity of structural and functional changes in the
      heart and vessels of the patients presenting with metabolic syndrome].
AB  - It is known that pathological characteristics of cardiac rhythm variability,
      endothelial dysfunction, and left ventricular hypertrophy may be used as
      independent predictors of cardiovascular complications; their combination with
      metabolic disorders increases severalfold the risk of cardiovascular
      catastrophes. The patients presenting with metabolic syndrome are characterized
      by the interrelation between melatonin hypersecretion, parameters of
      hyperactivity of the sympathetic component of the nervous system, and
      prognostically unfavourable variants of cardiac and vascular remodeling
      (including endothelial dysfunction, concentric remodeling and concentric
      myocardial ventricular hypertrophy). These correlations have age-specific
      peculiarities.

PMID- 22645960
TI  - [The character of alterations of electrophysiological properties of myocardium in
      the patients with arterial hypertension associated with type 2 diabetes
      mellitus].
AB  - The present study was designed to elucidate the character and severity of
      electrophysiological disturbances in the patients presenting with arterial
      hypertension (AH) associated with type 2 diabetes mellitus (DM). It included 55
      patients with AH (mean age 50.4 +- 4.7 years) allocated to two groups. Group 1
      was comprised of 25 patients with arterial hypertension and concomitant type 2
      diabetes mellitus. Group 2 (n = 30) consisted of the patients with AH in the
      absence of diabetes. All the patients were examined using 12-lead ECG and high
      resolution ECG (HR-ECG) supplemented by the analysis of late ventricular
      potentials (LVP) and cardiac rhythm variability (CRV). The study has demonstrated
      that diabetes mellitus in the patients suffering AH aggravates the disturbances
      in electrophysiological properties of myocardium compared with the patients
      having no metabolic disorders. These disturbances include changes of both
      repolarization and depolarization of myocardium. The patients with AH and
      concomitant diabetes mellitus had much higher values of dispersion and duration
      of QT-interval. Analysis of the results of HR-ECG in the two groups has revealed
      a significantly higher occurrence of late ventricular potentials in the patients
      with AH and concomitant type 2 DM (52% and 27% respectively; x2 = 4.43, p =
      0.03). Analysis of rhythmograms showed progressive deterioration of temporal and
      spectral characteristics of CRV in the group of patients with AH and concomitant
      type 2 DM. Moreover; these patients were characterized by the reduction of
      sympathetic and parasympathetic influences on myocardium.

PMID- 22645961
TI  - [Ulcer disease in schizophrenic patients as a model for the estimation of
      neurogenic factors predisposing to a somatic disease].
AB  - The objective of the present study was to elucidate specific clinical features of
      ulcer disease (UD), diseases associated with Helicobacter pylori infection, and
      motor disturbances in the upper portion of the gastrointestinal tract in the
      patients presenting with schizophrenia (n = 35). Their observation was based at a
      psychiatric hospital and a psychiatric dispensary, The control group was
      comprised of 80 psychically healthy subjects suffering ulcer disease. The program
      of examination included endoscopic and histological studies in conjunction with
      pathologoanatomic expertise. It was shown that ulcer disease in the patients with
      schizophrenia was characterized by the prevalence of gastric and combined forms
      of pathology (p = 0.001), the development of rare forms of ulcers of duodenal
      localization (p = 0.009), and motor disturbances in the upper portion of the
      gastrointestinal tract (p = 0.001) in conjunction with the impaired activity of
      Helicobacter pylori-associated gastritis (p < 0.05) when the development of the
      somatic disease preceded the onset of psychosis that, in its turn, was not
      precipitated by chronic alcoholism. Both the primary manifestation and the
      relapse of UD occurred either in the absence of a marked personality defect in
      the psychically ill patient or in the presence of chronic alcoholism concomitant
      with schizophrenia.

PMID- 22645962
TI  - [The role of epitheliocytes secreting vascular endothelial growth factor,
      pancreatic polypeptide and glucagon in the development of oncological diseases of
      the stomach].
AB  - The present study included 104 patients with gastric disorders associated with
      Helicobacter pylori infection. Thirty of them presented with chronic atrophic
      gastritis (CAG), 30 with gastric ulcer (GU), 20 with adenomatous gastric polyps
      (AGP), and 24 with gastric cancer (GC). The control group was comprised of 12
      practically healthy subjects. We elucidated the role of vascular endothelial
      growth factor (VEGF) and endocrine cells of gastric mucosa producing glucagon
      (GC) and pancreatic polypeptide (PPP) in the patients with GAG, GU, AGP and GC
      prior to and after the surgical intervention and following eradication therapy.
      It was shown that GAG, AGP, and GC were associated with the persistence of
      Helicobacter pylori infection and accompanied by hyperplasia of GC and PPP
      secreting endocrine cells of gastric mucosa. GU was characterized by hypolasia of
      VEGF-secreting epithelial cells of the stomach and GC and PPP-secreting endocrine
      cells of gastric mucosa. The levels of VEGF, GC and PPP that directly or
      indirectly realize their pathological properties through H. pylori, Bcl-2, and
      proapoptotic protein BAX proved to be of high prognostic value as regards the
      evolvement and clinical course of gastric disorders associated with Helicobacter
      pylori infection. The study demonstrated that adequate eradication therapy in
      patients with H. pylori-associated diseases of the stomach significantly reduces
      the number of gastric cells secreting VEGF and has practically no effect on the
      amount of GC and PPP-producing endocrine cells of gastric mucosa.

PMID- 22645964
TI  - [Antihypertensive efficacy of a low-dose combination of amlodipine and lisinopril
      in the treatment of arterial hypertension in postmenopausal women].
AB  - The present study had the objective to estimate the antihypertensive efficacy of
      a low-dose combination of amlodipine (5 mg) and lisinopril (equator, Gedeon
      Richter, Hungary; 10 mg) as well as its influence on the diastolic left
      ventricular function in the women presenting with arterial hypertension in the
      postmenopausal period A total of 60 postmenopausal women with grade II arterial
      hypertension available for the examination were allocated to two groups to be
      maintained on different therapeutic regimens. The study group was comprised of 40
      patients treated with equator, and the control group included 20 patients
      receiving metoprolol and enalapril (12.5 mg and 10 mg respectively). In the
      beginning and the end of the study (total duration 6 months), all the patients
      underwent a comprehensive clinical and instrumental examination that included
      evaluation of their general clinical condition, 24-hour arterial blood pressure
      monitoring (BPM), electrocardiography (ECG), and doppleroechocardiography. It was
      shown that therapy with equator significantly decreased systolic and diastolic
      arterial pressure (SAP and DAP). Comparative analysis of the results of repeated
      doppleroechocardiography revealed the improvement of left ventricular diastolic
      function in the majority of the patients of group 1 (83%). It is concluded that
      systematic treatment with equator produces a stable hypotensive effect and
      normalizes circadian rhythms of arterial pressure. Moreover, adequate
      antihypertensive therapy improves diastolic left ventricular function. Treatment
      with equator is well tolerated by the patients and causes no serious adverse
      effects.

PMID- 22645963
TI  - [The efficacy of cytoflavin used for the correction of psychoemotional and
      neuroimmune disturbances in the patients presenting with eczema].
AB  - Eczema is a commonest dermatological disease considered as classical
      psychosomatic cutaneous pathology with a neurological component. A total of 70
      patients with different forms of eczema were studied to estimate the effect of
      standard therapy on neuroimmunological laboratory characteristics, quality of
      life, psychoemotional status, clinical picture and its dynamics. The results were
      compared with the effects of cytoflavine, a substrate antihypoxant with
      antioxidative and neurotropic properties. Standard treatment did not eliminate
      psychoemotional and neuroimmune disturbances associated with eczema. Cytoflavine
      therapy yielded positive clinical and laboratory results giving reason to
      recommend this approach for the management of eczema in clinical practice.

PMID- 22645965
TI  - [Peculiarities of management of the elderly patients suffering from chronic
      obstructive pulmonary disease].
AB  - The authors present the results of an open prospective study undertaken to
      elucidate the influence of combined treatment of 72 patients presenting with
      chronic obstructive pulmonary disease (COPD). It was shown that traditional
      therapy supplemented by physical rehabilitation procedures, psychotherapy, and
      patient education during 6 months resulted in significant improvement of physical
      working capacity and mobility of the patients; moreover, it reduced the severity
      of apnea in the elderly subjects. The combined treatment of patients with COPD
      modulated the neuroimuunoendocrine status of their respiratory apparatus,
      enhanced the production of signal bronchodilatory molecules of vasoactive
      intestinal peptide, and decreased the level of bronchoconstrictor endothelin-1.
      It is concluded that the observed positive clinical and neuroimmunoendocrine
      effects of combined therapy give reason to recommend the use of this approach
      when providing the medical care for the elderly patients presenting with
      moderately severe COPD.

PMID- 22645966
TI  - [The frequency and structure of cardiac rhythm disturbances in the women
      presenting with abdominal obesity during the postmenopausal period].
AB  - We have studied the frequency and structure of cardiac rhythm (CR) disturbances
      in the women presenting with abdominal obesity (AO) in the postmenopausal period.
      The single-step study involved 210 postmenopausal women (median age 57 years) who
      were examined by 24-hour ECG monitoring, measurement of arterial pressure, body
      mass index, and the relationship between waist and hip circumferences. CR
      disturbances were revealed in all 159 women with abdominal obesity, ischemia in
      16.9%, supraventricular extrasystole in 89.3%, ventricular extrasystole (VE) in
      58.5%, high-grade extrasystole in 23.9%, paroxysms of supraventricular
      tachycardia in 1.9%, periods of asystole in 1.3%, synoatrial and atrioventricular
      blockade in 9.9%, His bundle branch block in 3.3%, sinus tachycardia in 48.8%,
      and sinus brachycardia in 23.9% of the patients. The risk of development of VE in
      the women with AO increased by 3.8 times in the presence of concomitant coronary
      heart disease and by 2.9 times in case of chronic cardiac failure. The frequency
      of VE was significantly higher in the patients with abdominal obesity than
      without it (odds ratio 2.2). It is concluded that women presenting with abdominal
      obesity during the postmenopausal period are characterized by the high frequency
      of cardiac rhythm disturbances and ischemia, with each fourth patient being at
      high risk of sudden death. The elevated risk of ventricular extrasystole in the
      postmenopausal period is associated with AO, coronary heart disease, and chronic
      heart failure. The frequency of VE is unrelated to ulcer disease, chronic
      cholecystitis, cholelithiasis, chronic pancreatitis, and impaired function of the
      thyroid gland.

PMID- 22645967
TI  - [The onset of myasthenia in a patient presenting with essential
      thrombocytopenia].
AB  - This paper describes the onset of a generalized form of myasthenia in a patient
      presenting with essential thrombocytopenia. Clinical features of myasthenia are
      considered. It is hypothesized that immunological disorders in the preceding
      period play an important role in the mechanisms triggering the onset of
      myasthenia.

PMID- 22645968
TI  - [Mixt: cases of hemorrhagic fever with hepatic syndrome and leptospirosis in a
      region of the Russian Federation endemic for these infections].

PMID- 22645969
TI  - [Evolution of metabolic syndrome: from polymetabolic disturbances to formation of
      nosological forms of the disease].

PMID- 22645970
TI  - [Memorable and milestone dates in the history of clinical medicine in 2011].

PMID- 22645971
TI  - [Olfactory system of crustaceans: structural, functional organization and
      perspectives of ecologo-toxicological studies].
AB  - Based on our own studies and literature data, we considered peculiarities of the
      structural-functional organization of the crustacean olfactory system and effect
      of pollutants on it. There are described changes of behavioral reactions based on
      chemoreception under conditions of pollution of the aquatic medium. Expedience of
      study of the crustacean olfactory system as a perspective object for ecologo
      toxicological studies is substantiated.

PMID- 22645972
TI  - [A modern viewpoint on structure and evolution of collagens. I. Fibrillar
      collagens].
AB  - This review summarizes current data on structure of the most representative group
      of the collagen family--fibrillar collagens. Attention has been focused on
      structural organization of individual domains and their functional role in the
      hierarchical stacking of alpha-chains of collagens. There is presented
      characteristics of the main stages of biosynthesis and of supramolecular
      processing of fibrillar collagens. Also considered are some aspects of evolution
      of fibrillar collagens. The role of duplication of genome and genes, intergene
      rearrangements, and exon shuffling in evolution of collagen genes is discussed.

PMID- 22645973
TI  - [Effect of temperature on proteinase activities of enteral microbiota and
      intestinal mucosa of fish of different ecological group].
AB  - Effect of temperature on proteinases activities of enteral microbiota and of
      intestinal mucosa was studied in five fish species (roach Rutilus rutilus,
      crucian carp Carassius carassius, common perch Perca fluviatilis, pike-perch
      Zander lucioperca, and pike Esox lucius) belonging by the nutrition type to
      different ecological groups. Essential differences of temperature characteristics
      of proteinases of intestinal mucosa and of enteral microbiota are revealed in
      fish belonging by the nutrition type to different ecologic groups. The character
      of the t0-function of proteinases of intestinal mucosa and enteral microbiota by
      casein and hemoglobin as a rule is different. The highest values of relative
      proteinases activities for casein in the zone of low temperatures (38 and 45.3 %
      of the maximal activity) are found at study of proteinases of enteral microbiota
      in common perch and crucian carp. The latter indicates a significant adaptability
      of the enteral microbiota proteinases of common perch and crucial carp to
      functioning at low temperatures.

PMID- 22645974
TI  - [Age-related changes in blood plasma antioxidant activity in population of the
      southern Altai].
AB  - The blood plasma antioxidant activity was studied in the Russian and Kazakh
      aborigines of the southern Altai low and high mountains. There was established a
      decrease of the blood plasma antioxidant activity with age and a relatively low
      plasma antioxidant activity in the mid-mountain population; in its senior age
      groups, the gender differences of this parameter were revealed.

PMID- 22645975
TI  - [Peculiarity of brain mechanisms of regulation of level of wakefulness and of
      cognitive activity in children with retardation of psychic development and in
      healthy children of the same AGF].
AB  - The work opens possibilities of the of modifications of the developed at the
      Laboratory systemic-integrative psychophysiological approach to study of the age
      related organization or of deviation from norm in formation of superslow
      informational-controlling brain systems participating in mechanisms of regulation
      of the wakefulness level and of cognitive activity in the 5-7-year old healthy
      children and in children of the same age group with retardation of psychic and
      speech development of the cerebral-organic genesis. There are disclosed
      peculiarities of organization of: (a) cortical-brainstem and limbic-reticular
      mechanisms of regulation of the level of wakefulness; (b) suprasegmentary
      mechanisms of autonomic, hemodynamic, and oxygen-dependent energy supply of the
      wakefulness level in the examined children's contingent. There are substantiated
      concepts about interrelations of peculiarities of the level of actual development
      of emotional and cognitive spheres with age-related peculiarities or disturbances
      of formation of mechanisms of regulation of the wakefulness level, its autonomic
      and hemodynamic provision as well as of the oxygen-dependent energetic potential.

PMID- 22645976
TI  - [Osmoregulatory reactions of frog erythrocytes under conditions of activation and
      blockade of Ca2+-channels].
AB  - The kinetics of cell osmoregulatory reactions under conditions of activation and
      blockade of Ca2+-channels was studied on a model of frog polyfunctional nuclear
      erythrocyte. Both activation and blockade of Ca2+-channels has been established
      to promote swelling of nuclei and an increase of the nuclear-cytoplasmic ratios
      under conditions of hypotonic exposure. The osmoregulatory cell reactions after
      activation of Ca2+-channels are expressed as a decrease of the cell volume. The
      blockator of Ca2+-channels verapamil produces an alternated increase and decrease
      of the erythrocyte volume with time intervals of 30 and 60 s. The clearly
      expressed functional activity of the nuclear membrane in response to the
      hypotonic action under conditions of activation and blockade of Ca2+-channels
      indicates participation of Ca2+ ions in mechanisms of the nuclear-cytoplasmic
      transfer.

PMID- 22645977
TI  - [A new model of depression induced by psychogenenic stress].
AB  - A new depression model has been obtained, based on use of stressors of the
      psychogenic nature. The laboratory rats in a special stress-camera turned out to
      be unable to induce the bilateral reaction of active avoidance, with subsequently
      led to formation of depression in the animals. Analysis of the tests sensitive to
      depression--a forceful swimming and a hanging by tail as well as of dynamics of
      the animals' body mass and of the behavior on the whole confirms development of
      their depression. This model has turned out to be sensitive to a selective
      inhibitor of the serotonin reuptake--fluoxetine; this also indicates our obtained
      model to be a model of depression.

PMID- 22645978
TI  - [Dynamics of folliculogenesis of sexually mature and neonatal ovarian tissue
      under conditions of long-term heterotopical transplantation].
AB  - In this work, a comparative analysis of dynamics of morphological development and
      endocrine function of transplants of sexually mature and neonatal ovarian tissue
      was performed under conditions of bilateral ovariectomy of animals-recipients. It
      has been established that at transplantation of the sexually mature ovarian
      tissue there were observed all stages of folliculogenesis and preservation of
      endocrine function at long-term observation (up to 100 days). At transplantation
      of neonatal ovarian tissue there was revealed a pathological picture of its
      development: hyperplasia of stromal structure and formation of cysts and
      cystomae. Follicles of different degree of maturity were revealed in 30 % of
      animals at the 30th day of observation. A significant increase of concentration
      of sex hormones as compared with ovariectomied animals has been shown only at
      early stages after implantation (30 days).

PMID- 22645979
TI  - [NO- and H2S-synthesizing neurons in thoracic ganglion of crabs Eriocheir
      japonicus and Pugettia quadreidens (Decapoda)].
AB  - By methods of histochemical marking of NADPH-diaphorase and immunohistochemical
      marking of cystathionine-beta-synthase (CBS), the presence and distribution of NO
      and H2S-synthesizing elements in thoracic ganglion are shown in two crab species
      Eriocheir japonicus and Pugettia quadreidens. In the thoracic ganglion, NO and
      H2S have been established to be synthesized by different neurons. The high CBS
      activity in efferent elements--segmentary motoneurons, interneurons, and nerve
      fibers in the extremity neuropil--indicates involvement of hydrogen sulfide in
      organization of the crustacean motor behavior. The presence of H2S-synthesizing
      neurons in the wall of sternal artery in E. japonicus allows suggesting
      participation of H2S in regulation of vascular tonus.

PMID- 22645980
TI  - [Comparative evaluation of morphofunctional organization of vertebrate nuclear
      blood cells].
AB  - Morphometrical parameters, osmoregulatory possibilities, and the membrane reserve
      value of nuclear hemocytes (leukocytes and erythrocytes) were studied in the main
      classes of vertebrates by using method of hypoosmotic loads. It has been
      established that in the fish--mammals line in erythrocytes the absolute reserve
      of the plasmalemma decreases and the relative area of the cell surface increases.
      Evolution of leukocytes is accompanied by an increase of the membrane reserve and
      of the surface area due to a decrease of volume and to a rise of folding of the
      plasmalemma.

PMID- 22645981
TI  - [Evolution of pulmonary respiration in mammals].

PMID- 22645982
TI  - [Structure of autorhythmical activity of contractile systems].
AB  - In the autorhythmical activity underlying many visceral and in early ontogenesis
      also somatomotor systems, three kinds of rhythms are to be distinguished: basic,
      reflecting activity of individual organs and of systems of organs, the secondary
      ones representing result of the frequency and amplitude modulation of the basic
      rhythms, and the rhythmical periodic activity whose distinguishing feature is
      alternation of the activity and rest phases. Each kind has principally different
      frequency characteristics, different organization and localization of sources.
      The frequency of basic rhythms is determined by the generator inserted into the
      system. It serves an individual characteristics of the current state of function
      of the organ, the degree of maturity of its motor apparatus. The secondary rhythm
      and the rhythm of the periodic activity cycles are provided by oscillatory
      processes common to the whole organism. Universality of these rhythms promotes
      integration of functions.

PMID- 22645983
TI  - [Cell technologies and the development of skin substitutes].
AB  - Large skin lesions might be of different cause and sometime resistant to the
      conventional and surgical treatment. For many years, skin grafting used to serve
      one of the most important methods to treat large and deep skin lesions. However,
      a limited availability of the substrate for transplantation restricts wider
      application of the approach. Utilization of wound covers and skin replacements of
      various types (including synthetic, biological and biosynthetic ones) provides an
      alternative. Skin substitutes--biosynthetic covers of the complex structure-
      constitute the most important niche in a wide spectrum of wound covers developed
      and actively utilized by today. Cell substrates used in the former include dermal
      fibroblasts, neonatal foreskin fibroblasts and keratinocytes. In the current
      review, key properties of the modern skin substitutes, structure features of the
      most widespread types. and principle of the work with the particular cell types
      are analyzed. Comparative analysis of the efficiency of wound covers is provided.

PMID- 22645985
TI  - [Analysis of the cell cycle duration of cells of permanent line L-929].
AB  - The direct measurement of the cell cycle duration in L-929 cells was performed
      using time-lapse photography. The cell cycle duration was 15.77 +/- 0.08 h with a
      standard deviation of 1.54 +/- 0.06 h. The experimental value fit to a normal
      distribution with a correlation coefficient 0.999. High homogeneity of this
      parameter and a wide range of variability of the karyotype (58-66 chromosomes)
      indicate that there is no correlation between these characteristics of L-929
      cells. It is also shown that the difference between cell cycle durations of
      daughter cells tent to zero and fits by an exponent.

PMID- 22645984
TI  - [The role of chromatoid bodies and cytoskeleton for differentiation of rat
      spermatozoids].
AB  - The ultrastructural and immunocytochemical study of rat male germ cells on
      different developing stages has been made. The investigation of morphological
      changes of spermatogenic cells has demonstrated the presence of tight connections
      between chromatoid bodies (CBs) and other cell organelles, particularly with the
      nucleus and Golgi apparatus; has revealed the association of manchette
      noncentrosomal microtubules (MT) with spermatid perinuclear ring plasma membrane
      (PM) in the zone of the adhesion intercellular contact--zonula adhaerens (ZA).
      The comparison of the results obtained in this work with available literary data
      has given possibility to analyze expected pathways of noncentrosomal MT
      nucleation in the late spermatids. This paper puts the supposition that
      noncentrosomal MTs are nucleated on the sites of perinuclear ring ZA. The
      immunocytochemical analysis discovered two novel proteins for these cells--BASP1
      and MARCKS. It has been shown that these proteins present in the CBs in the early
      spermatids. During the spermatozoid differentiation these proteins are revealed
      along the outer dense fibers (ODFs) of the sperm tail. BASP1 and MARCKS are
      supposed to involve in the processes of calcium accumulation in the CBs and ODFs.
      Calcium ions seem to play the significant role in RNA processing and protein
      synthesis in spermatids. Calcium is also necessary for the mobility of sperms
      which is mainly determined by ODFs.

PMID- 22645986
TI  - [Chromatin in diapause of the silkworm Bombyx mori L.: thermal parthenogenesis
      and normal development].
AB  - Having used hematoxylin as a stain, some features of silkworm embryo chromatin in
      diapause have been studied in normal and parthenogenetic development. With found
      direct correlation between the number of interphase chromatin grains and the
      number of chromosomes in the nucleus, we examined cell polyploidization in the
      embryo at diapause stage. Polyploidization by parthenogenesis is not reducible to
      endomitotic doubling of the chromosome set because it comprises 6n-nuclei.
      Explanation of more diverse range of polyploid cells in parthenogenesis needs to
      consider the fusion of cleavage nuclei that is carried out by the cytoplasmic
      karyogamic mechanism in the absence of fertilization. For the first time on
      squash preparations, in diapausing embryo, we have identified primary germ cells
      (PGC) that are characterized by less compact chromatin, especially in the zygotic
      form of development, a larger size of the nucleus and cytoplasm, and irregular
      number and size of nucleoli. Evaluation of PGC ploidy in parthenogenesis by
      calculation of "loose" chromatin grains in diapause is possible and testifies
      polyploidization in embryo germ-line. This explains the inevitable admixture of
      tetraploid eggs in diploid parthenoclone grain and its absence in normal
      development. Cytological method used has revealed a spiral arrangement of
      chromatin grains on the inner surface of the nucleus at different levels of
      ploidy.

PMID- 22645987
TI  - [Antineoplastic effect of hydrogel prospidin on Seidel ascites hepatoma used as a
      model].
AB  - Antineoplastic effect of hydrogel dextran phosphate, hydrogel prospidin, and
      prospidin in an injectable preparation has been assessed using Seidel ascites
      hepatoma as a model. Injectable and hydrogel prospidin in doses from 250, 500 to
      1000 mg/kg and hydrogel phosphate dextran in doses of 500 and 1000 mg/kg were
      administered to rats intraperitoneally in a single dose in a volume of 1 or 2 ml
      per each 100 g of animal body weight. The study has shown that irrespective of
      rats with Seidel ascites hepatoma and significantly increase in the dosage of
      prospidin preparations and hydrogel dextran phosphate results in a longer average
      life expectancy of rats Compared with its injectable variant, hydrogel prospidin
      appears to produce more than twice as high antineoplastic effect, and is found to
      provide prolonged therapeutic effects, as well as cure of animals in more than 60
      % of cases.

PMID- 22645988
TI  - [Response of Calliphora vicina larval hemocytes to abiotic and biotic foreign
      particles injection].
AB  - Human erythrocytes injection into the body cavity of Calliphora vicina
      postfeeding larvae results to their fast binding by thrombocytoidal fragments
      with agglutinates formation. There were almost none sites of lysis and
      degradation of erythrocytes in agglutinates even after shape modification and
      strands generation. Exceptions are zones of agglutinates with juvenile hemocytes,
      where destruction of erythrocytes is seen. The sequential injection of
      erythrocytes and charcoal particles leads to charcoal adhesion at first to
      agglutinates periphery and later to more deep stratum of cytoplasm between the
      erythrocytes. Under such conditions agglutinate formation period is accompanied
      with morphology variations which do not influence the intensity of agglutinating
      reaction. Juvenile plasmatocytes phagocytized the charcoal particles regardless
      of their concentration and duration of previous contact with erythrocytes. When
      mixture of abiotic and biotic particles was injected into post feeding larvae,
      crythrocytes and charcoal generate independent aggregations in the range of
      separate agglutinates. At the same time plasmatocytes form nodules consisting of
      temporary cell aggregations covered with cores of non phagocytized charcoal
      particles. These data testified that presumably lectin receptors responsible for
      foreign biotic and abiotic particles recognition are very near but not identical
      for different types of hemocytes. They may be specifical (for plasmatocytes) or
      integrated to different parts of cellular membrane (in thrombocytoids).

PMID- 22645989
TI  - [Functions of Calliphora vomitotia larval hemocytes in recognition and
      elimination from hemolymph human erythrocytes and charcoal particles].
AB  - Investigation of Calliphora vomitotia hemocyte defense reaction to human
      erythrocytes shows that erythrocytes are recognized mainly by thrombocytoids.
      Adhesion to plasmatocytes and subsequent phagocytosis also takes place, but in a
      less degree. Agglutination of erythrocytes by thrombocytoids is increased after
      feeding cessation and remains at a high level during all the period of crop
      emptying. Entrapped erythrocytes not later than after five to eight minutes show
      signs of destruction and disintegrate into fragments. Later structureless masses
      can arise. The results of secondary injections of charcoal particles reveal that
      both thrombocytoidal agglutinates and plasmatocytes can engulf additional abiotic
      invaders even after filling by erythrocytes. Meanwhile despite the changing
      morphology of agglutinates their capability to adhere new batches of aliens
      remains unchanged at enough high level. These agglutinates and plasmatocytes
      phagocytized the charcoal particles independently of previous erythrocyte
      exposition. Injection of charcoal and erythrocytes mixture leads to appearance of
      agglutinates with erythrocytes and charcoal mixed together. We guess that foreign
      receptors obtain wide spectrum of affinity to all kinds of invaders.

PMID- 22645990
TI  - [Effect of the liposomal form of taxifolin complexes with metals of variable
      valence on skin regeneration after chemical burn].
AB  - The effect of the liposomal form formed by taxifolin and metals of variable
      valency was investigated. It was shown that the application of preparations based
      on the free flavonoid and its complexes with Fe(II/III) and Cu(II) ions after
      chemical burns results in a more effective skin regeneration and the repair of
      hair follicles and sebaceous glands. A tendency for a more effective wound
      healing after the applications of taxifolin-Cu(II) and taxifolin-Fe(III)
      liposomal complexes versus control was observed. It was assumed that the
      mechanism of action of these preparations is based on the oxidative
      polymerization and conjugation of the flavonoid, which results in the utilization
      of toxic metabolites and lipid peroxidation products.

PMID- 22645991
TI  - [Mechanisms of radioresistance in terminally differentiated cells of mature
      retina].
AB  - Retinopathy of animals is induced by many agents damaging DNA. This fact shows
      that DNA lesions may initiate retinal degeneration. The aim of our work was to
      study the effects of gamma and proton irradiation, and methylnitrosourea (MNU) on
      mice retina. We evaluated morphological changes, DNA damage and repair in retina,
      and expression of 5 proteins participating in apoptosis: p53, ATM, FasR, PARP and
      caspase 3 active. Dose of 14 Gy is equitoxic in terms of induction of DNA single
      strand breaks by both gamma and proton irradiation. But protons were 2 fold more
      effective than gamma-rays in induction of DNA double strand breaks. All breaks
      were repaired within < or =10 h. Irradiation resulted in increased expression of
      p53 and ATM. But no sings of cell death and retinal degeneration were observed
      during 7 days after irradiation. Proton irradiation in dose of 25 Gy resulted in
      increasing over time destructive changes localized mainly in photoreceptor layer
      of retina. These changes were followed by increased expression of proapoptotic
      proteins. A single systemic administration of MNU (70 mg/kg) increased
      intracellular levels of p53, PARP, FasR, caspase 3 active, which was followed by
      destructive changes in retina with sings of apoptosis of photoreceptors. As in
      the case of irradiation, the 2-fold dose reduction of MNU abrogated cytotoxic
      effect of MNU on retina. High level of spontaneous DNA damage such as apurine and
      apyrimidine sites were observed in mouse retina. The results of our study
      demonstrate the occurrence of genotoxic threshold in the initiation of retinal
      cell death in vivo. Topoisomerase 2 of retina is suggested to translate primary
      DNA damage to cytotoxic effect.

PMID- 22645992
TI  - [The study of molecular mechanisms of action of natural amino acids and serotonin
      on adenylyl and guanylyl cyclases of the ciliates].
AB  - It has been previously shown that some amino acids and their derivatives are
      capable of regulating the activity of adenylyl cyclase (AC) and guanylate cyclase
      (GC) in free-living ciliates Dileptus anser and Tetrahymena. The aim of this work
      was to study the molecular mechanisms of action of methionine, tyrosine, alanine
      and neurohormone serotonin on the activity of enzymes-cyclases and the
      identification of their specific receptors in D. anser and T. pyriformis.
      Methionine and serotonin significantly increased the basal AC activity in both
      ciliates, and the AC effect of serotonin in T. pyriformis was carried out with
      the participation of Ca2+-dependent form of AC and heterotrimetic G proteins. AC
      stimulating effect of tyrosine and alanine was expressed weakly and only detected
      in D. anser. Serotonin is both ciliates and alanine in D. anser stimulated GC
      activity, whereas methionine and tyrosine had no effect on GC. Methionine and
      serotonin bind to surface receptors of the ciliates with high affinity. K(D) for
      [methyl-3H] methionine binding to D. anser and T. pyriformis were 7.5 and 35.6
      nM, and for [3H] serotonin binding were 2.7 and 4.7 nM, respectively. Alanine and
      tyrosine bind to the ciliates with low affinity. Thus, ciliates D. anser and T.
      pyriformis have chemosignaling systems regulated by amino acids and their
      derivatives and including the enzymes with cyclase activity. There is an
      assumption that these systems are similar to hormonal signaling systems of higher
      eukaryotes and are their predecessors.

PMID- 22645993
TI  - [Monocytic chemotaxic protein-1 and beta2-microglobulin: a role in estimation of
      renal parenchyma damage in surgical treatment of nephrolithiasis].
AB  - To estimate renal damage and intensity of tubulointerstitial fibrosis basing on
      the data of modern molecular markers in surgical treatment of nephrolithiasis, we
      examined the results of surgical treatment of 200 nephrolithiasis patients
      divided into 5 groups by the method of surgery. We estimated content of molecular
      mediators of nephrofibrosis in the urine and severity of renal dysfunction. We
      were the first to follow up urinary excretion of proinflammatory and profibrotic
      monocytic chemoattractant protein-1 (MCP-1) and low-molecular protein beta-2
      microglobulin which is a reliable indicator of tubular impairment. Our study
      demonstrated the highest efficacy and low traumatic risk of percutaneous
      nephrolithotripsy. We determined diagnostic levels of the studied laboratory
      indices which can be used for identification of impacts on nephrofibrosis
      processes.

PMID- 22645994
TI  - [Particular features of detection of patients with urogenital tuberculosis and
      their management].
AB  - The rate and trend in extrapulmonary tuberculosis (TB) incidence including
      urogenital tuberculosis (UTB) were estimated in population of the Sverdlovsk
      region for the last 25 years. Long-term results of treatment of 591 patients with
      different forms of UTB (renal parenchyma TB, tuberculosis papillitis,
      monocavernous and polycavernous renal TB, male genital TB) were studied. Ureter
      was involved in tuberculosis process in 24.7% of UTB cases, urinary bladder--in
      20.1%, renal TB combined with male genital TB. Early (non-destructive) forms
      incidence increased 2.8-fold while advanced forms incidence decreased 1.7-fold.
      This shows an increased level of detection. Total number of patients operated in
      state hospitals with undetected, mostly complicated urogenital male tuberculosis
      remains high--from 7.3 to 16% from all newly detected patients.

PMID- 22645995
TI  - [Methods of diagnosis and treatment of asymptomatic bacteriuria in postmenopausal
      women suffering from type 2 diabetes mellitus].
AB  - We studied prophylactic potential of local use of estriol in respect of urinary
      infections (UI) in postmenopausal women with asymptomatic bacteriuria (AB)
      suffering from type 2 diabetes mellitus (DM). A two-stage trial has been
      conducted. Stage one (a prospective study) was made to detect AB in DM women with
      AB. Of 414 female examinees AB was detected in 87 women. At stage two these women
      were randomized into two groups: group 1 received 0.5 mg estriol as vaginal
      cream, group 2 (control) received no prophylactic treatment. After 9 months of
      the trial AB was detected in 19.4% women of group 1 and 68.4% of the control
      group (p<0.001). Clinically significant UI was detected in 8.3 and 18.4%
      examinees (p<0.001), respectively. No correlation was found between AB
      development and a HbA1c level. Estriol treatment resulted in a rise of vaginal
      health index (VHI), appearance of lactobacteria in the vaginal smear, lowering of
      atrophic vaginitis detection rate. No significant changes were registered in the
      controls. Thus, local estriol administration effectively prevents and treats UI
      in postmenopausal females.

PMID- 22645996
TI  - [Combined action of levofloxacin and DNAase on biofilms of urogenital infection
      pathogens].
AB  - The effect of antibiotics and DNAase on biofilms of unrelated gram-positive and
      gram-negative bacteria was studied on strains isolated from patients with
      infectious and inflammatory urinary diseases. It was found that destruction of
      extracellular DNA biofilms by DNAase increases sensitivity of the bacteria to
      environmental factors including antibacterial drugs. DNAase addition to forming
      and formed biofilms created by unrelated bacteria leads to similar dose-dependent
      changes This evidences for universal action of the enzyme. A synergetic effect
      occurs in combined action of antibiotic biofilm and DNAase on bacteria.

PMID- 22645997
TI  - [Changes in plasmic and platelet hemostasis in patients with chronic renal
      failure in hemodialysis].
AB  - Plasmic and platelet components of hemostasis were examined in 50 patients with
      terminal chronic renal failure (CRF) aged 23 to 67 years and 30 healthy controls
      of the same age. A plasmic hemostasis component was studied basing on 11
      parameters of coagulogram. A platelet hemostasis component was studied by
      platelet aggregation: spontaneous and induced by ADP (in concentration 1.25, 2.5
      and 5.0 mkg/ml), collagen, adrenalin and ristomycin. All CRF patients before
      hemodialysis had a significant alterations of 6 indices of a plasmic component of
      hemostasis: activated partial thromboplastic time, content of soluble
      fibrinmonomeric complexes, thrombine time; of 3 from 7 tests of aggregatogram
      (ADP, collagen, ristomycin induced aggregation). After hemodialysis severity of
      the above pathological shifts deteriorated (1.5 to 5 times). Thus, CRF patients
      on hemodialysis showed aggrevation of impairment of all hemostasis components.
      They are at risk of hypercoagulation, DIC-syndrome, massive thromboembolism. The
      above impairment of hemostasis should be considered in prescription of
      anticoagulant therapy to CRF patients. Monitoring of hemodialysis and adequate
      correction of the hemostasis system defects may contribute to improvement of
      quality of life of patients with terminal CRF and lowering of their mortality
      rate.

PMID- 22645998
TI  - [Complications of mesh-vaginopexy: results of a multicenter trial].
AB  - A retrospective multicenter trial with participation of 7 large clinics of Moscow
      and Moscow Region has been performed to characterize complications after
      correction of genital prolapse with application of the PROLIFT system. The trial
      enrolled women with uterine and vaginal prolapse of stage II-IV by POP-Q
      classification. The women also had anatomic and functional defects of the
      adjacent organs. From January 2005 to March 2008 all the patients have undergone
      vaginal extraperitoneal colpopexy using Prolift system. The results of the trial
      showed that extraperitoneal colpopexy with application of the Prolift system
      should not be considered as a low-invasive intervention and therefore it is not
      valid to use this technique as a routine method of genital prolapse treatment as
      in 29.5% cases the operation is accompanied with complications of different
      severity.

PMID- 22645999
TI  - [The role of dysfunction of the autonomic nervous system in idiopathic overactive
      urinary bladder in women].
AB  - A complex urological and neurological examination of female patients with
      idiopathic overactive bladder (IOAB) has detected clinical signs and
      neurophysiological correlates of vegetative dysfunction in the form of disturbed
      sympatho-parasympathic interrelations, failure of segmental and compensatory
      enhancement of suprasegmental mechanisms of regulation of lower urinary tract
      activity. The treatment with selective inhibitors of serotonin re-entry reduced
      severity ofpsychovegetative syndrome and symptoms of the lower urinary tract.
      This confirms an essential role of the autonomic nervous system in pathogenetic
      mechanisms of IOAB development and gives grounds for recommending selective
      inhibitors of serotonin re-entry for combined treatment of IOAB patients.

PMID- 22646000
TI  - [ICIQ-SF questionnaire in women with urinary incontinence].
AB  - The ICIQ-SF questionnaire is used for evaluation of clinical manifestations in
      patients with urinary incontinence (UI) alone and combination of UI with lower
      urinary tract symptoms as well as assessment of quality of life in females with
      UI. Our study with ICIQ-SF questionnaire showed that UI was present in 23.8%
      responders. UI once a week or less often was marked most frequently by 11.6%
      women from all the age groups. Any volume of UI was marked by 24.5% women, most
      frequent volumes of urine loss were 15.9% and 7.1% in all age groups. Stress UI
      was prevalent in all the age groups (52.6%), the rate of urgent UI declined with
      age of women (16.3%), mixed UI rate, on the contrary, increased with age (26.7%).
      Significant frequency and volume of urine loss have the highest influence on
      quality of everyday women's life. Mixed UI reduced quality of life more
      significantly than stress and urgent UI. Thus, in view of high prevalence of UI
      among women, low compliance of the patients, the ICIQ-SF questionnaire can be
      recommended to therapists, gynecologists and urologists of the outpatient clinics
      for detection of UI in women. Response to ICIQ-SF questionnaire is a simple, easy
      to-make and cheap method of preliminary UI diagnosis and assessment of UI impact
      on quality of life.

PMID- 22646001
TI  - [Relations between red cell structure, function and immune homeostasis in
      prostatic diseases].
AB  - Patients with chronic prostatitis alone and in combination with prostatic adenoma
      have changes in the activity of the complement system, neutrophil function and
      content of pro- and anti-inflammatory cytokines. Abnormal representation of the
      proteins of the red cell membrane in patients with prostatic diseases affects
      structural and functional activity of erythrocytes in these patients. Dynamic
      changes in immune status of patients with chronic prostatitis and prostatic
      adenoma correlate with changes in functional red cell activity. This fact helps
      better understanding of pathogenesis of chronic prostatitis and prostatic
      adenoma.

PMID- 22646002
TI  - [Effects of L-carnitine on ejaculate parameters in males from infertile couples].
AB  - The aim of our investigation was detection of molecular mechanisms of an
      antioxidant action of L-carnitine (a transmembrane carrier of long-chain fatty
      acids) in idiopathic pathospermia. We treated 60 males from infertile couples
      with karniton (1 g/day). L-carnitine impact on ejaculate antioxidant status was
      assessed by registration of chemiluminescence and total antioxidant activity by
      colorimetric method according to changes in the color of ABTS chromogen. High
      dose-dependent antioxidant activity of the drug was found in testing on model
      systems in vitro. In vivo trials showed that patients given L-carnitine
      demonstrated a significant increase of the number of mobile spermatozoa of A
      category, positive changes in parameters of luminal-dependent and Fe2+ induced
      chemiluminescence of ejaculate in elevated antioxidant capacity of spermoplasma.
      After karniton treatment of the husbands 23% of their wives got pregnant. The
      treatment efficacy may be due to normalization of antioxidant status of
      ejaculate.

PMID- 22646003
TI  - [Urogenital diseases in men working "in shifts" in the oil fields of the Tyumen
      region].
AB  - Our study shows that urological health of men working in shifts in the oil fields
      of the Tyumen region is worse than mean national and regional characteristics.
      Newly diagnosed chronic bacterial prostatitis was prevalent among urogenital
      diseases. This situation can be explained by professional working and rest
      conditions for workers in the oil fields engaged in turn, by examination of the
      urologist participating in the health check-up team. Males with diagnosed
      prostatitis received treatment with the drug vitaprost plus produced in Russia
      with a good result.

PMID- 22646004
TI  - [Prostatic cancer detected at surgical treatment for prostatic adenoma].
AB  - We examined 408 patients operated for prostatic adenoma and estimated frequency
      of detection of incidental prostatic cancer (PC), determined PC clinical and
      pathological characteristics in patients exposed to preoperative prostatic biopsy
      and patients with no indications for such biopsy. The most significant factor in
      prognosis of the risk of cancer detection for patients exposed to biopsy is
      evidence obtained at finger rectal examination, transrectal ultrasound
      investigation, age; for patients unexposed to biopsy - PSA level is significant.

PMID- 22646005
TI  - [Retropubic adenomectomy in patients with a high level of prostate-specific
      antigen after prostatic biopsy].
AB  - Results of examination and treatment were analysed for 58 patients after
      retropubic adenomectomy performed from February 2008 to June 2010. The
      examination protocol included assessment of a total score of the scales IPSS and
      QoL, parameters of uroflowmetry, total PSA, the size of the prostate, number of
      prostatic biopsies in a high PSA level. The removed adenomatous tissue was
      examined histologically. By a PSA level, all the patients were divided into 3
      groups. Group 1 - 18 patients with a preoperative PSA level above 10 ng/ml, group
      2 - 23 patients with a PSA level from 4 to 10 ng/ml, group 3 - 17 control
      patients with PSA under 4 ng/ml. Mean age of the examinees was 67.7 +/- 7, 68.7
      +/- 7.7, 67.9 +/- 8.9 years (p>0.05), respectively. A mean PSA level was 20.9
      (10.3-53), 6.6 (4.1-9.9) and 2.4 (1.3-3.9) ng/ml (p<0.01), respectively. A mean
      size of the prostate was larger in group 1 patients than in the controls: 127.3
      (82-185) cm3 versus 100.7 (81-134) cm3 (p<0.05). Median of the number of
      transrectal multifocal biopsies was 2 (1-7), 1 (1-2) and 0 in groupl, 2 and 3,
      respectively. Histological examination of the adenomatous tissue detected
      prostatic adenocarcinoma in 0, 1(4.3%) and 1(5.9%) patients, respectively, while
      chronic prostatitis at different stages was diagnosed in 6(33.3%), 7(30.3%) and
      7(41.2%) patients, respectively. Thus, the above protocol of examination of
      patients with prostatic adenoma including measurement of a PSA level, conduction
      of finger rectal examination followed by prostatic biopsy (transrectal saturation
      procedure is preferable) provides performance of adenomectomy without a risk to
      miss a clinically significant prostatic cancer even in a PSA level above 10
      ng/ml.

PMID- 22646007
TI  - [Infertility in males with spinal cord trauma: state of the art].

PMID- 22646006
TI  - [Percutaneous puncture nephrolithotripsy in patients with horseshoe kidney].
AB  - To ascertain efficacy and specific features of percutaneous puncture
      nephrolithotripsy (TPNT) in concrements of the horseshoe kidney (HSK), we
      analysed the results of polyposition x-ray examination of 19 patients with HSK,
      modeling of percutaneous intervention on 3 cadever HSK and TPNT in 56 patients
      with concrements of HSK. The analysis showed that TPNT alone or in combination
      with extracorporeal lithotripsy destroyed the concrements which completely
      eliminated from the HSK in 48 (85.7%) patients. Specific features of TPNT in HSK
      concrements and relevant complications are characterized. Thus, TPNT in HSK
      concrements is an effective and low traumatic operation in patients with severe
      kidney anomalies.

PMID- 22646008
TI  - [Urgent andrological care in Moscow: current status and perspectives of the
      service].

PMID- 22646009
TI  - [The role of apoptosis Fas and Fasl markers in spermatogenesis].

PMID- 22646010
TI  - [Urological Clinic of the M. F. Vladimirsky Moscow Region Research Clinical
      Institute (1931-2011): per aspera ad nostrum].

PMID- 22646011
TI  - [Memorable dates in the history of urology and allied areas in 2012].

PMID- 22646012
TI  - Simple replacement reaction for the preparation of ternary Fe(1-x)PtRu(x)
      nanocrystals with superior catalytic activity in methanol oxidation reaction.
AB  - The finding of new metal alloyed nanocrystals (NCs) with high catalytic activity
      and low cost to replace PtRu NCs is a critical step toward the commercialization
      of fuel cells. In this work, a simple cation replacement reaction was utilized to
      synthesize a new type of ternary Fe(1-x)PtRu(x) NCs from binary FePt NCs. The
      detailed structural transformation from binary FePt NCs to ternary Fe(1-x)PtRu(x)
      NCs was analyzed by X-ray absorption spectroscopy (XAS). Ternary
      Fe(35)Pt(40)Ru(25), Fe(31)Pt(40)Ru(29), and Fe(17)Pt(40)Ru(43) NCs exhibit
      superior catalytic ability to withstand CO poisoning in methanol oxidation
      reaction (MOR) than do binary NCs (FePt and J-M PtRu). Also, the
      Fe(31)Pt(40)Ru(29) NCs had the highest alloying extent and the lowest onset
      potential among the ternary NCs. Furthermore, the origin for the superior CO
      resistance of ternary Fe(1-x)PtRu(x) NCs was investigated by determining the
      adsorption energy of CO on the NCs' surfaces and the charge transfer from Fe/Ru
      to Pt using a simulation based on density functional theory. The simulation
      results suggested that by introducing a new metal into binary PtRu/PtFe NCs, the
      anti-CO poisoning ability of ternary Fe(1-x)PtRu(x) NCs was greatly enhanced
      because the bonding of CO-Pt on the NCs' surface was weakened. Overall, our
      experimental and simulation results have indicated a simple route for the
      discovery of new metal alloyed catalysts with superior anti-CO poisoning ability
      and low usage of Pt and Ru for fuel cell applications.

PMID- 22646014
TI  - Discovery, development and effectiveness of coagulation-inhibiting drugs for
      stroke therapy.
AB  - INTRODUCTION: Stroke is the third leading cause of death in the US and the
      leading cause of major disability. A large variety of drugs and new therapeutic
      strategies are the basis for modern stroke therapy. There is scientific evidence
      for the effectiveness of only a few coagulation-inhibiting drugs for stroke
      prevention and treatment, but a lot of clinical trials have been conducted or are
      ongoing in order to gain more scientific data on stroke management and therapy.
      AREAS COVERED: This paper gives a general overview of modern coagulation
      inhibiting drugs discovered and investigated for prevention or acute stroke
      therapy and offers prospects of future therapy options. EXPERT OPINION: Without
      the development of more cost-effective future therapies and implementation of
      extended prevention programs, stroke will remain the leading cause of disability.
      There is still a strong need for the discovery of novel drug therapies that
      effectively avoid blood clotting and stroke without increasing the risk of
      hemorrhage.

PMID- 22646013
TI  - Aminoglycoside multiacetylating activity of the enhanced intracellular survival
      protein from Mycobacterium smegmatis and its inhibition.
AB  - The enhanced intracellular survival (Eis) protein improves the survival of
      Mycobacterium smegmatis (Msm) in macrophages and functions as the
      acetyltransferase responsible for kanamycin A resistance, a hallmark of
      extensively drug-resistant (XDR) tuberculosis, in a large number of Mycobacterium
      tuberculosis (Mtb) clinical isolates. We recently demonstrated that Eis from Mtb
      (Eis_Mtb) efficiently multiacetylates a variety of aminoglycoside (AG)
      antibiotics. Here, to gain insight into the origin of substrate selectivity of AG
      multiacetylation by Eis, we analyzed AG acetylation by Eis_Msm, investigated its
      inhibition, and compared these functions to those of Eis_Mtb. Even though for
      several AGs the multiacetylation properties of Eis_Msm and Eis_Mtb are similar,
      there are three major differences. (i) Eis_Msm diacetylates apramycin, a
      conformationally constrained AG, which Eis_Mtb cannot modify. (ii) Eis_Msm
      triacetylates paromomycin, which can be only diacetylated by Eis_Mtb. (iii)
      Eis_Msm only monoacetylates hygromycin, a structurally unique AG that is
      diacetylated by Eis_Mtb. Several nonconserved amino acid residues lining the AG
      binding pocket of Eis are likely responsible for these differences between the
      two Eis homologues. Specifically, we propose that because the AG-binding pocket
      of Eis_Msm is more open than that of Eis_Mtb, it accommodates apramycin for
      acetylation in Eis_Msm, but not in Eis_Mtb. We also demonstrate that inhibitors
      of Eis_Mtb that we recently discovered can inhibit Eis_Msm activity. These
      observations help define the structural origins of substrate preference among Eis
      homologues and suggest that Eis_Mtb inhibitors may be applied against all
      pathogenic mycobacteria to overcome AG resistance caused by Eis upregulation.

PMID- 22646015
TI  - Strategies to optimize the brain availability of central nervous system drug
      candidates.
AB  - INTRODUCTION: Access to the CNS is essential for most neurotherapeutics to elicit
      their effects. Leveraging design strategies incorporating physicochemical
      properties, in vitro and in vivo assays to predict and measure brain penetration,
      and brain delivery approaches may enable the drug discovery community to improve
      access of drug candidates into the CNS compartment. AREAS COVERED: This article
      reviews aspects of the most recent molecular design, in vitro and in vivo
      strategies, and delivery technologies to optimize the unbound brain
      concentrations (C (b,u)) of CNS molecules. Through this, the article provides
      insight into recent ideas and concepts in CNS drug molecule design, methods for
      evaluating CNS drug exposures and alternative approaches to maximize drug access
      to neurocompartments. EXPERT OPINION: The most pharmacologically relevant measure
      in assessing a compound's pharmacodynamic response in the CNS is its C (b,u). The
      utilization of emerging design strategies, together with in vitro and in vivo
      assays, may enable the design of molecules with optimal C (b,u):C (p,u) (C (p,u),
      unbound plasma concentration) and appropriate C (b,u,) to elicit a biological
      response from the neurotherapeutic target. Where drug properties intrinsically
      render a compound CNS impaired, using novel CNS delivery approaches may result in
      sufficient C (b,u) to furnish a biological response.

PMID- 22646016
TI  - Integrating fragmented software applications into holistic solutions: focus on
      drug discovery.
AB  - INTRODUCTION: Current advances in software development and global molecular
      profiling technologies allow the development of holistic software solutions for
      drug discovery. Such solutions must streamline in silico drug and therapy
      development by integrating all types of data into one knowledge base and also by
      enabling continuous analysis workflows uninterrupted by manual restructuring of
      inputs and outputs from workflow components. They must provide a collaborative
      environment for data sharing between multiple users and allow importing of all
      types of experimental data for subsequent analysis. AREAS COVERED: The reader is
      provided with a review of disparate software applications currently used in drug
      development and a discussion of existing organizational challenges for
      development of holistic software solutions. The reader is also provided with a
      proposed conceptual framework for integration of software components and some
      details for its implementation are suggested. EXPERT OPINION: Holistic solutions
      can undoubtedly affect the speed, quality and cost of drug development and
      personalized therapy. However, it must be constantly evolved to rapidly adopt new
      experimental and statistical methods, incorporate advances in software
      technologies and allow perpetual optimization of its components. Perpetual
      improvements in data structure, data quality, statistical algorithms and other
      mathematical approaches for computer modeling can gradually shift financial and
      cultural emphasis in the pharmaceutical industry away from traditional
      experimental approaches and towards computational approaches.

PMID- 22646017
TI  - Next generation histone deacetylase inhibitors: the answer to the search for
      optimized epigenetic therapies?
AB  - INTRODUCTION: HDAC inhibitors have demonstrated potent anticancer activities in
      preclinical and clinical studies. Currently, two drugs (SAHA and romidepsin) have
      gained the FDA approval for the treatment of cutaneous T-cell lymphoma. Clinical
      efficacy of HDAC inhibitors has been observed in advanced hematological
      malignancies, while response in other cancers has been in most cases
      unpredictable and often rather limited. The search for new molecules with the
      potential to overcome the limitations of the first HDAC inhibitors has become a
      primary goal in the field of epigenetic drug discovery as well as drugs acting on
      other chromatin modifying enzymes. AREAS COVERED: The article shortlists seven
      new HDAC inhibitors that have recently entered clinical studies as representative
      examples of next generation drugs. The most recently published preclinical
      profile is reviewed, together with the first clinical data for these compounds.
      The article then focuses on challenges faced during the progress of first
      generation HDAC inhibitors and analyzes whether these new compounds are likely to
      provide a solution to the existing issues and needs. EXPERT OPINION: Next
      generation HDAC inhibitors have the 'best-in-class' potential, particularly
      regarding potency and in vivo exposure. However, several issues remain
      unresolved. For example, none of the presented compounds appears to have a
      significantly different selectivity profile towards various HDAC isoforms and,
      thus, none of them may provide a further elucidation between the toxicity seen in
      more advanced HDAC inhibitors and isoform selectivity. Additionally, a need for a
      continuous effort on target validation is seen as a necessary requirement for
      further progress in the field.

PMID- 22646018
TI  - Non-stoichiometric inhibition in biochemical high-throughput screening.
AB  - INTRODUCTION: Over the last 2 decades, high-throughput screening (HTS) has become
      one of the key strategies for the generation of new leads. Non-stoichiometric
      inhibition is one of the most extensively studied mechanisms responsible for the
      large percentage of hit compounds from biochemical screens that cannot be
      developed into leads. Therefore, HTS hit lists need to be sorted rapidly and
      efficiently into stoichiometrically binding inhibitors and compounds that affect
      enzyme activity non-stoichiometrically. AREAS COVERED: This article explores the
      non-stoichiometric inhibition of enzymatic activity in biochemical screens,
      particularly by compound aggregation, and the authors explain the terminology
      they use to describe such compound behavior. The paper then provides a short
      historical overview of both academic and industrial research on compound
      aggregation specifically. Finally, the article discusses the implications for
      industrial drug discovery and the measures that can be taken to identify non
      stoichiometric and aggregating inhibitors early in this process. EXPERT OPINION:
      The most pragmatic approach in a lead finding campaign is to focus on the early
      identification of selective and stoichiometric inhibitors. The combination of
      multiple approaches (assessing both activity and binding) allows the enrichment
      of stoichiometric inhibitors at each stage of the flowchart.

PMID- 22646019
TI  - Human immunodeficiency virus-1 gp120 V3 loop for anti-acquired immune deficiency
      syndrome drug discovery: computer-aided approaches to the problem solving.
AB  - INTRODUCTION: The V3 loop on gp120 from HIV-1 is a focus of many research groups
      involved in anti-AIDS drug development because this region of the protein is the
      principal target for neutralizing antibodies and determines the preference of the
      virus for T-lymphocytes or primary macrophages. AREAS COVERED: This review
      summarizes findings related to the 3D structure, conformational mobility,
      function, antigenicity and immunogenicity of the HIV-1 V3 loop. Particular
      consideration is given to the V3 loop core sequence Gly-Pro-Gly-Arg/Gln-Ala-Phe,
      which forms the HIV-1 gp120 immunogenic tip, the role of which has not been
      completely determined in the virus pathogenesis. New computer-aided approaches
      for designing potential HIV-1 entry inhibitors are illustrated by a series of
      examples in which promising basic structures for the V3-based anti-AIDS drug
      researches have been constructed. Special focus is given to recent studies aimed
      at defining the structurally conservative V3 sites that may present the HIV-1
      weak points most suitable for therapeutic intervention. Finally, the article also
      discusses how this information can be used to develop novel, potent and broad
      anti-AIDS agents. EXPERT OPINION: Data on the structure and function of the HIV-1
      V3 loop prove convincingly that, in spite of disappointing progress > 20 years,
      this mysterious site of gp120 (comprising at least three structural motifs
      recurring in various viral isolates) still remains one of the most attractive
      targets for the anti-AIDS drug development.

PMID- 22646020
TI  - A drug discovery case history of 'delta-9-tetrahydrocannabinol, cannabidiol'.
AB  - INTRODUCTION: Although the Cannabis sativa herb has been known for its
      therapeutic benefit for centuries, the interest in the clinical potential of
      cannabinoid-based drugs escalated after the discovery of the endocannabinoid
      system. The understanding of their actions at the molecular level indicates that
      the therapeutic applications of cannabinoids (plant-derived or synthetic) may be
      diverse. Several drugs containing cannabinoids are currently used in the therapy
      of emesis, pain and spasticity. AREAS COVERED: This drug discovery case history
      reviews the preclinical and clinical development of Sativex ('delta-9
      tetrahydrocannabinol, cannabidiol'; nabiximols). Sativex is the first licensed
      phytocannabinoid-based drug approved, or in the process of approval, as therapy
      for indications such as MS-associated spasticity or chronic pain. Sativex
      contains a combination of two cannabinoids in approximately equal quantities
      (delta-9-tetrahydrocannabinol and cannabidiol) and is administered via an
      oromucosal pump spray, aiming at minimising psychotropic side effects and first
      pass effect. Pivotal clinical safety and efficacy data that led to Sativex's
      approval are discussed, as well as issues that have arisen with its clinical
      usage. EXPERT OPINION: Although pleiotrophic effects of cannabinoids may raise
      complex issues beyond their symptomatic effects, standardised pharmaceutical
      cannabinoids may constitute a useful addition to the pharmacotherapeutic
      armamentarium in chronic conditions insufficiently alleviated by existing drugs.

PMID- 22646021
TI  - The 18th European symposium on quantitative structure-activity relationships.
AB  - The 18th European Symposium on Quantitative Structure-Activity Relationships
      (QSAR) took place in Rhodes, Greece, on 19 - 24 September 2010. It was organized
      by the Hellenic Society of Medicinal Chemistry and the Cheminformatics and QSAR
      Society, and co-sponsored by the European Federation of Medicinal Chemistry. The
      conference was thematically dedicated to discovery informatics and drug design
      and addressed the impact of informatics in all its variants (chemoinformatics,
      bioinformatics, pharmacoinformatics) on drug discovery in the broader context of
      biological complexity. The latest scientific and technological advances in QSAR
      as tools for the discovery of new, safer and more efficacious drugs were
      discussed during the meeting. This paper highlights the most important outcomes
      of the symposium, commenting briefly on some of the key presentations.

PMID- 22646022
TI  - Adipokines and the cardiovascular system: mechanisms mediating health and
      disease.
AB  - This review focuses on the role of adipokines in the maintenance of a healthy
      cardiovascular system, and the mechanisms by which these factors mediate the
      development of cardiovascular disease in obesity. Adipocytes are the major cell
      type comprising the adipose tissue. These cells secrete numerous factors, termed
      adipokines, into the blood, including adiponectin, leptin, resistin, chemerin,
      omentin, vaspin, and visfatin. Adipose tissue is a highly vascularised endocrine
      organ, and different adipose depots have distinct adipokine secretion profiles,
      which are altered with obesity. The ability of many adipokines to stimulate
      angiogenesis is crucial for adipose tissue expansion; however, excessive blood
      vessel growth is deleterious. As well, some adipokines induce inflammation, which
      promotes cardiovascular disease progression. We discuss how these 7
      aforementioned adipokines act upon the various cardiovascular cell types
      (endothelial progenitor cells, endothelial cells, vascular smooth muscle cells,
      pericytes, cardiomyocytes, and cardiac fibroblasts), the direct effects of these
      actions, and their overall impact on the cardiovascular system. These were
      chosen, as these adipokines are secreted predominantly from adipocytes and have
      known effects on cardiovascular cells.

PMID- 22646023
TI  - OLSVis: an animated, interactive visual browser for bio-ontologies.
AB  - BACKGROUND: More than one million terms from biomedical ontologies and controlled
      vocabularies are available through the Ontology Lookup Service (OLS). Although
      OLS provides ample possibility for querying and browsing terms, the visualization
      of parts of the ontology graphs is rather limited and inflexible. RESULTS: We
      created the OLSVis web application, a visualiser for browsing all ontologies
      available in the OLS database. OLSVis shows customisable subgraphs of the OLS
      ontologies. Subgraphs are animated via a real-time force-based layout algorithm
      which is fully interactive: each time the user makes a change, e.g. browsing to a
      new term, hiding, adding, or dragging terms, the algorithm performs smooth and
      only essential reorganisations of the graph. This assures an optimal viewing
      experience, because subsequent screen layouts are not grossly altered, and users
      can easily navigate through the graph. URL: http://ols.wordvis.com CONCLUSIONS:
      The OLSVis web application provides a user-friendly tool to visualise ontologies
      from the OLS repository. It broadens the possibilities to investigate and select
      ontology subgraphs through a smooth visualisation method.

PMID- 22646024
TI  - Preventing injury from child aggression: a single-case evaluation of the effects
      of staff-worn protective equipment.
AB  - OBJECTIVE: This single-case study of a boy with autism and high-frequency
      aggression concerned the effects of classroom teachers wearing protective
      equipment (gloves) on injuries produced to their hands as well as injuries
      sustained to non-protected areas of the body. METHODS: A reversal-type design was
      used to evaluate the effects of protective equipment relative to a baseline (no
      protective equipment) phase, a low-demand activity phase without protective
      equipment and a low-demand activity phase with protective equipment. RESULTS: The
      protective equipment intervention eliminated hand injuries, did not result in
      other types of injuries, was not associated with increased aggression and was
      rated favourably by the classroom teachers. CONCLUSION: The findings suggest that
      staff-worn protective equipment may be a valuable component of comprehensive
      clinical safety programmes within service settings for children with intellectual
      and developmental disabilities.

PMID- 22646026
TI  - Man and molecules.

PMID- 22646025
TI  - A New ACS Audio Course to help you understand and solve industrial and municipal
      waste-water problems ....

PMID- 22646028
TI  - Letters.

PMID- 22646029
TI  - Manuscript processing time.

PMID- 22646030
TI  - Washington.

PMID- 22646032
TI  - Science.

PMID- 22646031
TI  - International.

PMID- 22646034
TI  - Industry.

PMID- 22646033
TI  - States.

PMID- 22646036
TI  - Environmental dispute resolution.

PMID- 22646035
TI  - Technology.

PMID- 22646037
TI  - Exposure pathways of workplace contaminants.

PMID- 22646039
TI  - Quality control in water analyses.

PMID- 22646038
TI  - EPA's cancer policy.

PMID- 22646041
TI  - Literature.

PMID- 22646040
TI  - Products.

PMID- 22646043
TI  - Courses.

PMID- 22646045
TI  - professional consulting services directory.

PMID- 22646046
TI  - Index to the advertisers in this issue.

PMID- 22646047
TI  - The role of surface charge of nucleation agents on the crystallization behavior
      of poly(vinylidene fluoride).
AB  - The effect of the surface charge of nucleation agents on the crystallization
      behavior of poly(vinylidene fluoride) (PVDF) has been investigated. Ion-dipole
      interaction between the positive surface of nucleation agents and the partially
      negative CF(2) dipoles of PVDF is established as a main factor for further
      lowering the free energy barrier for nucleation, and thus increasing
      significantly the crystallization kinetics. This is in contrast to the behavior
      observed for nucleation agents possessing either negative surface or neutral
      charges. Positive nucleation agents led to a remarkable increase in the
      crystallization temperature of PVDF (lower supercooling) as compared with that of
      neat PVDF. The dispersion of each type of nucleation agent is also important. The
      melting temperatures of nucleation agents need to be higher than the melting
      temperature of PVDF. The melting point and degree of crystallinity of PVDF can
      also be raised by using specific nucleation agents. The detailed crystallization
      kinetics and conformational changes of the PVDF chain have been investigated.
      With the addition of positive nucleation agents, the gamma and beta chain
      conformations, instead of the alpha phase, dominate.

PMID- 22646049
TI  - Unboosted atazanavir for treatment of HIV infection: rationale and
      recommendations for use.
AB  - Atazanavir (Reyataz(r)) is a protease inhibitor (PI) for the treatment of HIV
      infection. Several trials have demonstrated the good efficacy and toxicity
      profile of atazanavir boosted by ritonavir (atazanavir/r). However, several
      toxicity events and pharmacokinetic issues due to drug-to-drug interactions
      (partly related to ritonavir) may complicate atazanavir/r therapy. This is why
      regimens with unboosted atazanavir have been experimented with and are used in
      clinical practice. The aim of this article is to identify the clinical settings
      in which unboosted atazanavir may be a safe and effective option for the long
      term control of HIV replication. Despite the fact that a favourable lipid profile
      and good gastrointestinal tolerability have been reported in comparative trials,
      unboosted atazanavir should not be considered an optimal choice for treatment
      naive patients. In fact, boosting with ritonavir produces higher atazanavir
      plasma levels, which are beneficial in terms of efficacy, especially in untreated
      patients with high plasma HIV RNA. Clinical data indicate that, in patients with
      sustained undetectable HIV RNA and without previous virological failure or HIV
      drug resistance-associated mutations, a switch to unboosted atazanavir-based
      regimens is a feasible option to control and prevent toxicity events, especially
      in patients who cannot tolerate ritonavir and in those with severe
      hyperbilirubinaemia on atazanavir/r. Moreover, while unboosted atazanavir must
      not be used in pregnant women, it is a recommended option in special populations,
      such as patients with moderate liver insufficiency. Lastly, unboosted atazanavir
      in combination with raltegravir may allow the construction of a well tolerated
      and effective regimen without nucleoside reverse transcriptase inhibitors in
      patients for whom these drugs are contraindicated. In conclusion, there is a good
      rationale, significant clinical interest and accumulating clinical experience
      with unboosted atazanavir-based regimens, although this formulation should be
      used only in specific situations and as a maintenance strategy. Moreover,
      therapeutic drug monitoring could be useful in specific circumstances (such as in
      patients with liver impairment or in case of potential drug-drug interactions).

PMID- 22646050
TI  - Inferior progression-free survival for Thai patients with diffuse large B-cell
      lymphoma treated under Universal Coverage Scheme: the impact of rituximab
      inaccessability.
AB  - The impact of health insurance with inequitable rituximab coverage on the
      survival of patients with diffuse large B-cell lymphoma (DLBCL) has never been
      reported. We conducted a nationwide multicenter analysis on the outcome of 553
      adult patients consecutively diagnosed with DLBCL between July 2003 and June
      2006, in whom treatment cost was reimbursed under the Civil Servant Medical
      Benefit Scheme (CSMBS) (n =201) or the Universal Coverage Scheme (UCS) (n =352).
      The international prognostic index was comparable between the two payment groups.
      Rituximab-based therapy was administered in 45.3% and 3.1% of CSMBS and UCS
      patients, respectively (p <0.001). With a median follow-up of 24.6 months, the 6
      year progression-free survival (PFS) was superior for CSMBS patients (34.2 vs.
      23.2%, p =0.005). "Not treated with rituximab-based therapy" was the strongest
      adverse prognostic feature indicating a short PFS (hazard ratio 2.1, p <0.001).
      It is concluded that lack of access to rituximab is the principal factor
      accounting for the inferior PFS observed in Thai patients with DLBCL who are
      treated under the UCS.

PMID- 22646051
TI  - Real-time observation of the swelling and hydrolysis of a single crystalline
      cellulose fiber catalyzed by cellulase 7B from Trichoderma reesei.
AB  - The biodegradation of cellulose involves the enzymatic action of cellulases
      (endoglucanases), cellobiohydrolases (exoglucanases), and beta-glucosidases that
      act synergistically. The rate and efficiency of enzymatic hydrolysis of
      crystalline cellulose in vitro decline markedly with time, limiting the large
      scale, cost-effective production of cellulosic biofuels. Several factors have
      been suggested to contribute to this phenomenon, but there is considerable
      disagreement regarding the relative importance of each. These earlier
      investigations were hampered by the inability to observe the disruption of
      crystalline cellulose and its subsequent hydrolysis directly. Here, we show the
      application of high-resolution atomic force microscopy to observe the swelling of
      a single crystalline cellulose fiber and its-hydrolysis in real time directly as
      catalyzed by a single cellulase, the industrially important cellulase 7B from
      Trichoderma reesei. Volume changes, the root-mean-square roughness, and rates of
      hydrolysis of the surfaces of single fibers were determined directly from the
      images acquired over time. Hydrolysis dominated the early stage of the
      experiment, and swelling dominated the later stage. The high-resolution images
      revealed that the combined action of initial hydrolysis followed by swelling
      exposed individual microfibrils and bundles of microfibrils, resulting in the
      loosening of the fiber structure and the exposure of microfibrils at the fiber
      surface. Both the hydrolysis and swelling were catalyzed by the native cellulase;
      under the same conditions, its isolated carbohydrate-binding module did not cause
      changes to crystalline cellulose. We anticipate that the application of our AFM
      based analysis on other cellulolytic enzymes, alone and in combination, will
      provide significant insight into the process of cellulose biodegradation and
      greatly facilitate its application for the efficient and economical production of
      cellulosic ethanol.

PMID- 22646052
TI  - Mean platelet volume/platelet count ratio in anemia.

PMID- 22646055
TI  - Relationship between interleukin-6 and ammonia in patients with minimal hepatic
      encephalopathy due to liver cirrhosis.
AB  - AIM:   Previous studies have shown significantly elevated levels of interleukin
      (IL)-6 in cirrhotic patients with minimal hepatic encephalopathy (MHE), but the
      relationship between circulating levels of IL-6 and ammonia is unclear. The aim
      of this study is to investigate the relationship between both variables in
      cirrhotic patients with MHE. METHODS:   Psychometric tests including number
      connection test part A (NCT-A) and digit symbol test (DST) were performed to
      diagnose MHE in 85 cirrhotic patients. Simultaneously, circulating levels of IL-6
      and ammonia were measured. RESULTS:   Thirty-two (37.6%) cirrhotic patients were
      diagnosed with MHE. IL-6 and ammonia were the independent predictors of the
      presence of MHE (P < 0.05 for both variables). Circulating levels of IL-6 and
      ammonia correlated with the severity of MHE represented by results of NCT-A (r =
      0.56, P < 0.05 and r = 0.39, P < 0.05, respectively) and DST (r = -0.48, P < 0.05
      and r = -0.47, P < 0.05, respectively). Moreover, there was a significant
      correlation between circulating levels of IL-6 and those of ammonia in patients
      with MHE (r = 0.61, P < 0.05), and a positive additive interaction was found
      between IL-6 and ammonia on the presence of MHE, with a significant synergy index
      of 1.51 (95% confidence interval = 1.12-3.46). CONCLUSION:   The present study
      demonstrates a significant correlation and a positive additive interaction
      between IL-6 and ammonia in cirrhotic patients with MHE, suggesting that IL-6 may
      have a potential synergistic relationship with ammonia in the induction of MHE.

PMID- 22646056
TI  - Effect of positioning from supine and left lateral positions to left lateral tilt
      on maternal blood flow velocities and waveforms in full-term parturients.
AB  - Positioning the parturient from supine to the left lateral tilt position (supine
      to-tilt) may not effectively displace the gravid uterus, but turning from the
      left lateral position to the left lateral tilt position (left lateral-to-tilt)
      may keep the gravid uterus displaced and prevent aortocaval compression. Fifty
      one full-term parturients were randomly placed in the left lateral position,
      supine-to-tilt and left lateral-to-tilt positions using a Crawford wedge. Femoral
      vein area, femoral vein velocity, femoral artery area, pulsatility index,
      resistance index and right arm mean arterial blood pressure and heart rate were
      recorded. Our results showed a lower mean (SD) femoral vein area (82.2 (14.9) vs
      96.2 (16.4) mm(2)), a lower pulsatility index (3.83 (1.3) vs 5.8 (2.2)), a lower
      resistance index (0.93 (0.06) vs 0.98 (0.57)), a higher femoral artery area (33.3
      (3.8) vs 30.9 (4.4) mm(2)) and a higher femoral vein velocity (7.9 (1.2) vs 6.1
      (1.6) cm.s(-1)) with left lateral-to-tilt when compared with supine-to-tilt (all
      p < 0.001). Our results suggest that moving a full-term parturient from the full
      left lateral to the lateral tilt position may prevent aortocaval compression in
      full-term parturients more efficiently than when positioning the parturient from
      a supine to left lateral tilt position.

PMID- 22646057
TI  - Concentration-dependent mechanisms of cell penetration and killing by the de novo
      designed antifungal hexapeptide PAF26.
AB  - Recent evidence indicates that antimicrobial peptides can kill microbes in more
      complex ways than just by membrane permeabilization. In this study, the mechanism
      of internalization of the de novo designed cationic hexapeptide PAF26 has been
      characterized in detail using Neurospora crassa. Live-cell imaging of
      fluorescently labelled PAF26, organelle probes and mutants indicate that the
      peptide is endocytically internalized at low fungicidal concentrations (2.0-5
      uM). At these concentrations, PAF26 initially accumulated in vacuoles that
      expanded, and then was actively transported into the cytoplasm, which coincided
      with cell death. Deletion mutants of the endocytic proteins RVS-161, RVS-167 and
      RAB-5 exhibited reduced rates of PAF26 internalization and fungicidal activity.
      Pharmacological experiments with live-cell probes showed that PAF26
      internalization and antifungal action at low fungicidal concentrations was energy
      dependent, primarily actin-mediated, and disrupted intracellular calcium
      homeostasis. PAF26 antifungal activity at low concentrations was shown to rely on
      its endocytic internalization. PAF26 also induced plasma membrane depolarization
      which, however, was independent of peptide internalization and killing of fungal
      cells. At high fungicidal concentrations (20 uM), PAF26 internalization was
      energy-independent, suggesting the involvement of passive peptide translocation.
      Our results provide new mechanistic insights into the mode-of-action of small
      cationic antimicrobial peptides that should facilitate improvements in their
      design.

PMID- 22646058
TI  - Phenotypic selection to increase floral scent emission, but not flower size or
      colour in bee-pollinated Penstemon digitalis.
AB  - Fragrance is a putatively important character in the evolution of flowering
      plants, but natural selection on scent is rarely studied and thus poorly
      understood. We characterized floral scent composition and emission in a common
      garden of Penstemon digitalis from three nearby source populations. We measured
      phenotypic selection on scent as well as floral traits more frequently examined,
      such as floral phenology, display size, corolla pigment, and inflorescence
      height. Scent differed among populations in a common garden, underscoring the
      potential for scent to be shaped by differential selection pressures. Phenotypic
      selection on flower number and display size was strong. However, selection
      favoured scent rather than flower size or colour, suggesting that smelling
      stronger benefits reproductive success in P. digitalis. Linalool was a direct
      target of selection and its high frequency in floral-scent bouquets suggests that
      further studies of both pollinator- and antagonist-mediated selection on this
      compound would further our understanding of scent evolution. Our results indicate
      that chemical dimensions of floral display are just as likely as other components
      to experience selective pressure in a nonspecialized flowering herb. Therefore,
      studies that integrate visual and chemical floral traits should better reflect
      the true nature of floral evolutionary ecology.

PMID- 22646060
TI  - IGF2/H19 hypomethylation in a patient with very low birthweight, preocious
      pubarche and insulin resistance.
AB  - BACKGROUND: Insulin like growth factor 2 (IGF2) is an imprinted gene, which has
      an important role in fetal growth as established in mice models. IGF2 is
      downregulated through hypomethylation of a differentially methylated region (DMR)
      in Silver Russell syndrome (SRS), characterised by growth restriction. We have
      previously reported that severe pre- and post-natal growth restriction associated
      with insulin resistance and precocious pubarche in a woman without body asymmetry
      or other SRS features resulted from a balanced translocation affecting the
      regulation of her IGF2 gene expression. We hypothesised that severe pre- and post
      natal growth restriction associated with insulin resistance and precocious
      pubarche in the absence of SRS are also caused by downregulation of IGF2 through
      hypomethylation, gene mutation or structural chromosomal abnormalities. METHODS:
      We performed routine karyotyping, IGF2 gene sequencing and investigated DNA
      methylation of the IGF2 differentially methylated region (DMR)0 and H19 DMR using
      pyrosequencing, in four women selected for very low birth weight (<-3 SDS for
      gestational age), precocious pubarche, short adult stature (<-2 SDS), and insulin
      resistance (defined as HOMA-IS < 80%); and compared their methylation results to
      those of 95 control subjects. RESULTS: We identified a 20 year old woman with
      severe hypomethylation at both DMRs. She was the smallest at birth (birthweight
      SDS,-3.9), and had the shortest adult height (143 cm). The patient was diagnosed
      with polycystic ovarian syndrome at the age of 15 years, and had impaired fasting
      glucose in the presence of a low BMI (19.2 kg/m2). CONCLUSIONS: Our case of
      growth restriction, premature pubarche and insulin resistance in the absence of
      body asymmetry or other features of SRS adds to the expanding phenotype of
      IGF2/H19 methylation abnormalities. Further studies are needed to confirm whether
      growth restriction in association with premature pubarche and insulin resistance
      is a specific manifestation of reduced IGF2 expression.

PMID- 22646061
TI  - Awareness and opinions of non-alcoholic fatty liver disease by hospital
      specialists.
AB  - BACKGROUND/AIM: Subjects with metabolic risk factors for non-alcoholic fatty
      liver disease (NAFLD) are commonly seen by hospital specialists other than
      gastroenterologists/hepatologists. The aim of this study was to assess the
      awareness of NAFLD and opinions regarding management among non-hepatologists at
      two major tertiary hospitals in Brisbane. METHODS: A face-to-face questionnaire
      assessing current beliefs and practices regarding NAFLD was administered to
      specialists and specialists-in-training across six specialties (internal
      medicine, cardiology/cardiac surgery, endocrinology, thoracic medicine,
      rheumatology and nephrology). RESULTS: One hundred clinicians were surveyed with
      99% returning completed questionnaires (>89% questions answered). The majority of
      respondents (75%) believe the prevalence of NAFLD in the general population to be
      <= 10%, although two-thirds feel that its incidence will rise markedly. The vast
      majority (>90%) appreciate that traditional cardiovascular risk factors (obesity,
      hypertriglyceridaemia and diabetes) are risk factors for NAFLD and acknowledge
      that these are common in non-hepatology patients. Despite this, most believe that
      NAFLD is uncommon in their own patients (89% indicated a prevalence <= 30%). The
      vast majority (93%) agree that non-alcoholic steatohepatitis (NASH) is associated
      with increased overall mortality, but 60% also believe that simple steatosis
      confers increased liver-related mortality. Most (74%) agree that a diagnosis of
      NASH cannot be made using liver enzymes, but 67% support 6-monthly liver function
      tests as the most effective way to monitor progression of NAFLD. Most respondents
      (71%) make no referrals to hepatology for suspected NAFLD. CONCLUSIONS: Non
      hepatologists appreciate the seriousness of NAFLD but appear to underestimate its
      prevalence, especially among their own patients despite known risk factors.
      Attitudes regarding simple steatosis versus NASH and appropriate monitoring of
      suspected NAFLD suggest that more can be done to improve the understanding of
      this disease among non-hepatologists. This has implications for targeting 'at
      risk' populations and appropriate referral of patients to hepatology clinics.

PMID- 22646063
TI  - Lessons drawn from research utilization in the maternal iodine supplementation
      policy development in Thailand.
AB  - In this paper, the authors share their experience on evidence utilization in the
      development of Thailand's maternal iodine supplementation policy in 2009-2010.
      Observations and reflections on their experience of engaging with research for
      policymaking are illustrated. The case study indicates that rapid approaches in
      conducting research, namely a targeted literature review and cross-sectional
      survey of professionals' opinions and current practices were efficient in
      achieving the timeliness of evidence provision. In addition pro-activity, trust
      and interaction between researchers and policymakers enhanced the research-policy
      integration. The Thai experience may be useful for other developing countries
      which pursue evidence-informed policymaking, despite differences in the health
      system context.

PMID- 22646062
TI  - A Fur-like protein PerR regulates two oxidative stress response related operons
      dpr and metQIN in Streptococcus suis.
AB  - BACKGROUND: Metal ions are important micronutrients in cellular metabolism, but
      excess ions that cause toxic reactive oxygen species are harmful to cells. In
      bacteria, Fur family proteins such as Fur, Zur and PerR manage the iron and zinc
      uptake and oxidative stress responses, respectively. The single Fur-like protein
      (annotated as PerR) in Streptococcus suis has been demonstrated to be involved in
      zinc and iron uptake in previous studies, but the reports on oxidative stress
      response and gene regulation are limited. RESULTS: In the present study, the perR
      gene deletion mutant DeltaperR was constructed in Streptococcus suis serotype 2
      strain SC-19, and the mutant strain DeltaperR exhibited less sensitivity to H2O2
      stress compared to the wild-type. The dpr and metQIN were found to be upregulated
      in the DeltaperR strain compared with SC-19. Electrophoretic mobility shift
      assays showed that the promoters of dpr and metQIN could be bound by the PerR
      protein. These results suggest that dpr and metQIN are members of the PerR
      regulon of S. suis. dpr encodes a Dps-like peroxide resistance protein, and the
      dpr knockout strains (Deltadpr and DeltadprDeltaperR) were highly sensitive to
      H2O2. MetQIN is a methionine transporter, and the increased utilization of
      methionine in the DeltaperR strain indirectly affected the peroxide resistance.
      Using a promoter-EGFP gene fusion reporting system, we found that the PerR
      regulon was induced by H2O2, and the induction was modulated by metal ions.
      Finally, we found that the pathogenicity of the perR mutant was attenuated and
      easily cleared by mice. CONCLUSIONS: These data strongly suggest that the Fur
      like protein PerR directly regulates dpr and metQIN and plays a crucial role in
      oxidative stress response in S. suis.

PMID- 22646064
TI  - Comparison of patient acceptance of sodium phosphate versus polyethylene glycol
      plus sodium picosulfate for colon cleansing in Japanese.
AB  - BACKGROUND AND AIM: In Japan, patient acceptance of bowel preparation methods
      before colonoscopy remains unknown. This study was conducted to evaluate the
      patient acceptance of sodium phosphate (NaP) tablets and polyethylene glycol
      solution (PEG) with sodium picosulfate. METHODS: One hundred patients were
      randomized into one of the following two groups: the NaP tablet first-use group
      or the PEG with sodium picosulfate first-use group in a crossover design trial.
      Patient acceptance and incidence of adverse events were evaluated using a
      questionnaire. Colon-cleansing effectiveness was also evaluated. RESULTS:
      Patients' overall impressions of the preparations were significantly different
      between the NaP tablet (77.9%, 67/86) and PEG with sodium picosulfate (60.5%,
      52/86; P = 0.001). Nausea incidence as an adverse event was significantly
      different between the two regimens (P = 0.03). Colon-cleansing effectiveness was
      not significantly different between the two regimens. CONCLUSIONS: The results of
      this crossover study showed that patient acceptance was similar to those
      previously reported in a parallel-group comparison. In Japanese patients,
      preference for and acceptance of NaP tablets was significantly higher than that
      for PEG with sodium picosulfate solution.

PMID- 22646059
TI  - Diversification and phylogeographic structure in widespread Azteca plant-ants
      from the northern Neotropics.
AB  - The Neotropical myrmecophytic tree Cordia alliodora hosts symbiotic Azteca ants
      in most of its widespread range. The taxonomy of the genus Azteca is notoriously
      difficult, which has frequently obscured species identity in ecological studies.
      We used sequence data from one mitochondrial and four nuclear loci to infer
      phylogenetic relationships, patterns of geographic distribution, and timing of
      diversification for 182 colonies of five C. alliodora-dwelling Azteca species
      from Mexico to Colombia. All morphological species were recovered as
      monophyletic, but we identified at least five distinct genetic lineages within
      the most abundant and specialized species, Azteca pittieri. Mitochondrial and
      nuclear data were concordant at the species level, but not within species.
      Divergence time analyses estimated that C. alliodora-dwelling Azteca shared a
      common ancestor approximately 10-22million years ago, prior to the proposed
      arrival of the host tree in Middle America. Diversification in A. pittieri
      occurred in the Pleistocene and was not correlated with geographic distance,
      which suggests limited historical gene flow among geographically restricted
      populations. This contrasts with the previously reported lack of phylogeographic
      structure at this spatial scale in the host tree. Climatic niches, and
      particularly precipitation-related variables, did not overlap between the sites
      occupied by northern and southern lineages of A. pittieri. Together, these
      results suggest that restricted gene flow among ant populations may facilitate
      local adaptation to environmental heterogeneity. Differences in population
      structure between the ants and their host trees may profoundly affect the
      evolutionary dynamics of this widespread ant-plant mutualism.

PMID- 22646065
TI  - The impact of cerebrospinal fluid biomarkers on the diagnosis of Alzheimer's
      disease.
AB  - The cerebrospinal fluid (CSF) biomarkers beta-amyloid(1-42) (Abeta(1-42)), total
      tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau(181P)) are
      gradually finding their way into routine clinical practice as an affirmative
      diagnostic tool for Alzheimer's disease (AD). These biomarkers have also been
      implemented in the revised diagnostic criteria for AD. The combination of the CSF
      biomarkers Abeta(1-42), T-tau, and P-tau(181P) leads to high (around 80%) levels
      of sensitivity, specificity, and diagnostic accuracy for discrimination between
      AD and controls (including psychiatric disorders like depression) and can be
      applied for diagnosing AD in the predementia phases of the disease (mild
      cognitive impairment). The added value of CSF biomarkers could lie within those
      cases in which the clinical diagnostic work-up is not able to discriminate
      between AD and non-AD dementias. However, their discriminatory power for the
      differential diagnosis of dementia is suboptimal. Other CSF biomarkers,
      especially those that are reflective of the pathology of non-AD dementia
      etiologies, could improve the accuracy of differential dementia diagnosis. CSF
      biomarkers will be of help to establish a correct and early AD diagnosis, even in
      the preclinical stages of the disease, which will be of importance once disease
      modifying drugs for AD become available. Variation in biomarker measurements
      still jeopardize the introduction of CSF biomarkers into routine clinical
      practice and clinical trials, but several national and international
      standardization initiatives are ongoing.

PMID- 22646068
TI  - The ISBT 700 series of low-incidence and 901 series of high-incidence blood group
      antigens.
AB  - The International Society of Blood Transfusion Working Party on Terminology for
      Red Cell Surface Antigens developed a terminology that brought order to the chaos
      of antigen names. They classified antigens into three categories: systems,
      collections, and series. This review summarizes the early decisions of the
      Working Party with an emphasis on the 700 series of low-incidence antigens and
      901 series of high-incidence antigens.

PMID- 22646067
TI  - Glycopyrrolate oral solution: for chronic, severe drooling in pediatric patients
      with neurologic conditions.
AB  - Chronic drooling (sialorrhea) is a common dysfunction in children with neurologic
      disorders such as cerebral palsy. Glycopyrrolate oral solution, an
      anticholinergic agent, is the first drug treatment approved in the US for
      drooling in children with neurologic conditions. This article reviews the
      clinical efficacy and tolerability of glycopyrrolate oral solution in pediatric
      patients with neurologic conditions and provides an overview of the
      pharmacological properties of the drug. In a phase III, randomized, double-blind,
      multicenter trial, children (aged 3-16 years; n = 36) with problem drooling
      associated with neurologic conditions and receiving glycopyrrolate oral solution
      had a significantly (p < 0.01) greater modified Teacher's Drooling Scale (mTDS)
      response rate at 8 weeks (primary endpoint) than those receiving placebo (73.7%
      vs 17.6%). At 24 weeks in an additional, noncomparative, phase III study, 52.3%
      of glycopyrrolate oral solution recipients (aged 3-18 years; n = 137) had an mTDS
      response (primary endpoint); the response rate was consistently above 50% at all
      4-weekly timepoints, aside from the first assessment at week 4 (40.3%). In
      general, glycopyrrolate oral solution was well tolerated in clinical trials. The
      majority of adverse events were within expectations as characteristic
      anticholinergic outcomes.

PMID- 22646069
TI  - The LW blood group system: a review.

PMID- 22646070
TI  - Determination of optimal method for antibody identification in a reference
      laboratory.
AB  - Methods commonly used for antibody identification are hemagglutination (tube),
      column agglutination (gel), and solid-phase red cell adherence. Our AABB
      immunohematology reference laboratory (IRL) conducted a study to determine which
      antibody identification testing method was optimal for detecting all clinically
      significant antibodies. Patient specimens were sent to our IRL from August 2008
      to September 2009. Routine testing was performed by tube method and then by
      manual gel and manual solid-phase methods. Of the 254 samples tested, 115 showed
      agreement in antibody identification with all three methods. The tube method
      identified all but six clinically significant antibodies. The gel method did not
      identify 59 clinically significant antibodies. Fifty-six clinically significant
      antibodies were not identified by solid-phase testing. Tube testing identified 27
      clinically insignificant antibodies, primarily cold autoantibodies. Gel and solid
      phase methodologies identified two and three cold autoantibodies, respectively.
      Solid-phase testing failed to detect 12 examples of anti-K. No identifiable
      pattern of reactivity was found in 13 samples using gel testing compared with 6
      for solid-phase and none for tube methodologies. Hemagglutination tube method was
      the best choice for our IRL because it missed the fewest number of clinically
      significant alloantibodies. Benefits also included the ability to use various
      potentiating factors, incubation times, and temperature phases to enhance
      antibody identification. The tube method provided critical data for determining
      antibody clinical significance.

PMID- 22646071
TI  - Preoperative coagulation studies to predict blood component usage in coronary
      artery bypass graft surgery.
AB  - Bleeding remains a serious complication of cardiac surgery. Studies indicate that
      preoperative fibrinogen concentration is an independent predictor of blood loss
      during coronary artery bypass graft (CABG) surgery. This study evaluates whether
      fibrinogen concentration is a better predictor of blood usage than the
      prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests.
      Patients not taking clopidogrel bisulfate who underwent CABG surgery during a 3
      month period at a 350-bed community hospital were included in this prospective
      study. The parameters evaluated included patient's age, preoperative coagulation
      test results (PT, international normalized ratio [INR], aPTT, fibrinogen), and
      number of blood components transfused. A probability value of less than 0.05 was
      deemed significant. Thirty-five patients were included in this study. Mean blood
      usage was 6 units. Patient's age approached significance as a predictor of blood
      usage, and fibrinogen levels trended toward significance more than the other
      coagulation parameters. In this study, the increased age of the patient and low
      plasma concentrations of fibrinogen were associated with increased blood usage.
      Although no indicators clearly demonstrated statistical significance, the vast
      difference in the probability values for patients' ages and fibrinogen levels
      indicated that there was a trend toward significance in blood usage for CABG
      patients. Further studies with larger patient populations are indicated.

PMID- 22646072
TI  - Prospects for neurodegenerative and psychiatric disorder drug discovery.
AB  - The discovery of CNS-active drugs has, to a major extent, resulted from clinical
      serendipity. Once targets for such compounds were identified, conventional
      mechanism-based approaches were used to identify new chemical entities for the
      treatment of neurological and psychiatric disorders. Most of these have, however,
      failed to display any greater efficacy than existing psychotherapeutics and may,
      in fact, be less efficacious because of side effect liabilities. Among the
      reasons for this lack of success in drug discovery include a lack of fundamental
      knowledge regarding the causes of CNS disorders, the absence of biomarkers for
      diagnosing and monitoring these conditions, a paucity of animal models that are
      congruent with the human disease state and the increasing likelihood that CNS
      conditions are multifactorial in their etiology. These challenges force the
      inclusion of a Phase IIa proof of concept trial as a component of the drug
      discovery program. Unlike other therapeutic areas, serendipity is a major factor
      in the CNS translational medicine interface requiring a close collaboration
      between preclinical and clinical scientists trained to appreciate unusual
      behavioral phenotypes. When combined with conventional target-based drug
      discovery technologies, this increases the likelihood of identifying truly novel
      drugs for the treatment of CNS disorders.

PMID- 22646074
TI  - In silico screening strategies for novel inhibitors of parasitic diseases.
AB  - INTRODUCTION: Parasitic diseases are a major global problem causing long-term
      disability and death, with severe medical and psychological consequences around
      the world. Despite the prevalence of parasitic disease, the treatment options for
      many of these illnesses are still inadequate and there is a dire need for new
      antiparasitic drugs. In silico screening techniques, which are powerful
      strategies for hit generation, are widely being applied in the design of new
      ligands for parasitic diseases. AREAS COVERED: This article analyses the
      application of ligand- and structure-based virtual screening strategies against a
      variety of parasitic diseases and discusses the benefits of the integration
      between computational and experimental approaches toward the discovery of new
      antiparasitic agents. The analysis is illustrated by recent examples, with
      emphasis on the strategies reported within the past 2 years. EXPERT OPINION:
      Virtual screening techniques are powerful tools commonly used in drug discovery
      against parasitic diseases, which have provided new opportunities for the
      identification of several novel compound classes with antiparasitic activity.

PMID- 22646073
TI  - Lessons from high-throughput protein crystallization screening: 10 years of
      practical experience.
AB  - INTRODUCTION: X-ray crystallography provides the majority of our structural
      biological knowledge at a molecular level and, in terms of pharmaceutical design,
      is a valuable tool to accelerate discovery. It is the premier technique in the
      field, but its usefulness is significantly limited by the need to grow well
      diffracting crystals. It is for this reason that high-throughput crystallization
      has become a key technology that has matured over the past 10 years through the
      field of structural genomics.     Areas covered  :     The authors describe their
      experiences in high-throughput crystallization screening in the context of
      structural genomics and the general biomedical community. They focus on the
      lessons learnt from the operation of a high-throughput crystallization-screening
      laboratory, which to date has screened over 12,500 biological macromolecules.
      They also describe the approaches taken to maximize the success while minimizing
      the effort. Through this, the authors hope that the reader will gain an insight
      into the efficient design of a laboratory and protocols to accomplish high
      throughput crystallization on a single-, multiuser laboratory or industrial
      scale.     Expert opinion  :     High-throughput crystallization screening is
      readily available but, despite the power of the crystallographic technique,
      getting crystals is still not a solved problem. High-throughput approaches can
      help when used skillfully; however, they still require human input in the
      detailed analysis and interpretation of results to be more successful.

PMID- 22646076
TI  - Making sense of therapeutics using antisense technology.
AB  - INTRODUCTION: Antisense oligonucleotides (ASOs) are short synthetic single
      stranded DNA sequences that bind to and induce the cleavage of homologous
      stretches of mRNA sequences. These result in targeted destruction of mRNA and
      correction of genetic aberrations. ASOs thus can act as drug molecules and
      potentially rectify many disease conditions. The broad range of applications
      reported in the literature highlights the advances in the field. AREAS COVERED:
      This review covers different areas in which use of ASOs has been shown to have
      therapeutic effects. Some drugs in different stages of preclinical and clinical
      trials are discussed in detail. The problems faced and the strategies to surmount
      them are also described. The readers will gain an understanding of the recent
      developments in the field of ASOs with emphasis on their therapeutic
      applications. They will also become aware of the different strategies used for
      targeted delivery of ASOs and their stabilization, which may be useful for their
      work in this field, or in the area of nucleic acid therapeutics in general.
      EXPERT OPINION: The design and application of ASOs for recognition of target mRNA
      sequences have become a fairly straightforward protocol. The main problem lies in
      designing ASOs which are stable in in vivo milieu. The delivery and
      bioavailability of the oligonucleotide to the site of action continue to be
      hurdles in the development of ASOs and therapeutic molecules.

PMID- 22646075
TI  - The design and screening of drugs to prevent acquired sensorineural hearing loss.
AB  - INTRODUCTION: Sensorineural hearing loss affects a high percentage of the
      population. Ototoxicity is a serious and pervasive problem in patients treated
      with cisplatin. Strategies to ameliorate ototoxicity without compromising on
      antitumor activity of treatments are urgently needed. Similar problems occur with
      aminoglycoside antibiotic therapy for infections. Noise-induced hearing loss
      affects a large number of people. The use of ear protection is not always
      possible or effective. The prevention of hearing loss with drug therapy would
      have a huge impact in reducing the number of people with hearing loss from these
      major causes. AREAS COVERED: This review discusses significant research findings
      dealing with the use of protective agents against hearing loss caused by
      cisplatin, aminoglycoside antibiotics and noise trauma. The efficacy in animal
      studies and the application of these protective agents in clinical trials that
      are ongoing are presented. EXPERT OPINION: The reader will gain new insights into
      current and projected future strategies to prevent sensorineural hearing loss
      from cisplatin chemotherapy, aminoglycoside antibiotic therapy and noise
      exposure. The future appears to offer numerous agents to prevent hearing loss
      caused by cisplatin, aminoglycoside antibiotics and noise. Novel delivery systems
      will provide ways to guide these protective agents to the desired target areas in
      the inner ear and circumvent problems with therapeutic interference of antitumor
      and antibiotics agents as well as minimize undesired side effects.

PMID- 22646077
TI  - New opportunities in drug design of metalloproteinase inhibitors: combination
      between structure-function experimental approaches and systems biology.
AB  - INTRODUCTION: MMPs (matrix metalloproteinases) and ADAMs (a disintegrin and
      metalloproteinases) are endopeptidases central to the degradation and remodeling
      of the extracellular matrix. These proteases also exhibit regulatory activity in
      cell signaling pathways and thus tissue homeostasis under normal conditions and
      in many diseases. Consequently, individual members of the MMP and ADAM protein
      families were identified as important therapeutic targets. However, designing
      effective inhibitors in vivo for this class of enzymes appears to be extremely
      challenging. This is attributed to the broad structural similarity of their
      active sites and to the dynamic functional interconnectivity of MMPs with other
      proteases, their inhibitors, and substrates (the so-called degradome) in healthy
      and disease tissues. AREAS COVERED: The article covers the progress in designing
      metalloproteinase inhibitors, based on recent advancements in our understanding
      of enzyme structures and their function as master regulators. It also discusses
      the potential of utilizing structure-based drug design strategies in conjunction
      with systems biology experimental approaches for designing potent and
      therapeutically effective metalloproteinase inhibitors. EXPERT OPINION: We
      highlight the use of protein-based drug design strategies, for example,
      antibodies and protein scaffolds, targeting extracatalytic domains, which are
      central to proteolytic and non-proteolytic enzyme functions. Such rationally
      designed function-blocking inhibitors may create new opportunities in disease
      management and in emerging therapies that require control of dysregulated MMP
      activity without causing severe side effects. Importantly, the lessons learned
      from studying these protein-based inhibitors can be implemented to design new and
      effective small or medium sized synthetic antagonists.

PMID- 22646079
TI  - 99mTc-albumin can replace 125I-albumin to determine plasma volume repeatedly.
AB  - OBJECTIVE: Plasma volume assessment may be of importance in several disorders.
      The purpose of the present study was to compare the reliability of plasma volume
      measurements by technetium-labeled human serum albumin ((99m)Tc-HSA) with a
      simultaneously performed plasma volume determination with iodine-labeled human
      serum albumin ((125)I-HSA). MATERIALS AND METHODS: In 15 healthy volunteers,
      simultaneous plasma volume measurements with (99m)Tc-HSA and (125)I-HSA were
      performed after 1/2 hour in the supine position. Blood samples were obtained 10,
      15, 20, and 30 minutes after the injection for accurate retropolation from the
      plasma counts to time zero to correct for leakage of the isotopes from the
      circulation. RESULTS: The mean difference (bias) between plasma volume measured
      with (125)I-albumin and (99m)Tc-albumin was 8 ml (0.1 ml/kg) with limits of
      agreement (bias +/-1.96 SD) ranging from -181-196 ml (-2.3-2.5 ml/kg). The tracer
      disappearance rate was significantly higher with (99m)Tc-albumin (-23.1+/-7.1%/h)
      than with (125)I-albumin (-6.7+/-3.6%/h) (p <0.001). CONCLUSION: This study
      demonstrates that (99m)Tc-HSA can replace (125)I-HSA for single measurements of
      plasma volume in healthy volunteers. It needs to be emphasized however, that
      repeated blood sampling for 1/2 hour after injection of the tracer is required to
      correct for the disappearance of (99m)Tc and (99m)Tc-HSA from the circulation.

PMID- 22646080
TI  - Understanding native Russian listeners' errors on an English word recognition
      test: model-based analysis of phoneme confusion.
AB  - OBJECTIVE: Word recognition is a basic component in a comprehensive hearing
      evaluation, but data are lacking for listeners speaking two languages. This study
      obtained such data for Russian natives in the US and analysed the data using the
      perceptual assimilation model (PAM) and speech learning model (SLM). DESIGN:
      Listeners were randomly presented 200 NU-6 words in quiet. Listeners responded
      verbally and in writing. Performance was scored on words and phonemes (word
      initial consonants, vowels, and word-final consonants). STUDY SAMPLE: Seven
      normal-hearing, adult monolingual English natives (NM), 16 English-dominant (ED),
      and 15 Russian-dominant (RD) Russian natives participated. ED and RD listeners
      differed significantly in their language background. RESULTS: Consistent with the
      SLM, NM outperformed ED listeners and ED outperformed RD listeners, whether
      responses were scored on words or phonemes. NM and ED listeners shared similar
      phoneme error patterns, whereas RD listeners' errors had unique patterns that
      could be largely understood via the PAM. RD listeners had particular difficulty
      differentiating vowel contrasts /i-I/, /ae-epsilon/, and /alpha-Lambda/, word
      initial consonant contrasts /p-h/ and /b-f/, and word-final contrasts /f-v/.
      CONCLUSIONS: Both first-language phonology and second-language learning history
      affect word and phoneme recognition. Current findings may help clinicians
      differentiate word recognition errors due to language background from hearing
      pathologies.

PMID- 22646078
TI  - Approaches to the rational design of selective melanocortin receptor antagonists.
AB  - INTRODUCTION: When establishing the physiological roles of specific receptors in
      normal and disease states, it is critical to have selective antagonist ligands
      for each receptor in a receptor system with several subtypes. The melanocortin
      receptors have five subtypes referred to as the melanocortin 1 receptor,
      melanocortin 2 receptor, melanocortin 3 receptor, melanocortin 4 receptor and
      melanocortin 5 receptor, and they are of critical importance for many aspects of
      human health and disease. AREAS COVERED: This article reviews the current efforts
      to design selective antagonistic ligands for the five human melanocortin
      receptors summarizing the currently published orthosteric and allosteric
      antagonists for each of these receptors. EXPERT OPINION: Though there has been
      progress, there are still few drugs available that address the many significant
      biological activities and diseases that are associated with these receptors,
      which is possibly due to the lack of receptor selectivity that these designed
      ligands are currently showing. The authors believe that further studies into the
      antagonists' 3D conformational and topographical properties in addition to future
      mutagenesis studies will provide greater insight into these ligands which could
      play a role in the treatment of various diseases in the future.

PMID- 22646082
TI  - Neurodevelopmental outcomes in children with Angelman syndrome after 1 year of
      behavioural intervention.
AB  - OBJECTIVE: To examine the impact of teaching approaches based on the principles
      of applied behaviour analysis (ABA) on neurodevelopmental outcomes in children
      with Angelman syndrome (AS). METHODS: A non-randomized pre-test-post-test control
      group design was used. The intervention group consisted of four children with AS
      aged 3.1-9.2 years. Controls were other children with AS who were individually
      matched on the basis of chronological age, gender and molecular sub-type.
      Children in the intervention group were provided two-to-three ABA-based therapy
      sessions per week over a 1-year period. Standardized measures of cognitive,
      adaptive and language functioning were administered at baseline and after 1 year.
      RESULTS: There were no statistically significant differences between the two
      groups at baseline or after 1 year. However, positive trends were observed in the
      intervention group for some cognitive and adaptive measures. CONCLUSION: ABA
      based intervention improved aspects of neurodevelopment for some children with AS
      and warrants further study.

PMID- 22646081
TI  - Mechanical environment modulates biological properties of oligodendrocyte
      progenitor cells.
AB  - Myelination and its regenerative counterpart remyelination represent one of the
      most complex cell-cell interactions in the central nervous system (CNS). The
      biochemical regulation of axon myelination via the proliferation, migration, and
      differentiation of oligodendrocyte progenitor cells (OPCs) has been characterized
      extensively. However, most biochemical analysis has been conducted in vitro on
      OPCs adhered to substrata of stiffness that is orders of magnitude greater than
      that of the in vivo CNS environment. Little is known of how variation in
      mechanical properties over the physiological range affects OPC biology. Here, we
      show that OPCs are mechanosensitive. Cell survival, proliferation, migration, and
      differentiation capacity in vitro depend on the mechanical stiffness of polymer
      hydrogel substrata. Most of these properties are optimal at the intermediate
      values of CNS tissue stiffness. Moreover, many of these properties measured for
      cells on gels of optimal stiffness differed significantly from those measured on
      glass or polystyrene. The dependence of OPC differentiation on the mechanical
      properties of the extracellular environment provides motivation to revisit
      results obtained on nonphysiological, rigid surfaces. We also find that OPCs
      stiffen upon differentiation, but that they do not change their compliance in
      response to substratum stiffness, which is similar to embryonic stem cells, but
      different from adult stem cells. These results form the basis for further
      investigations into the mechanobiology of cell function in the CNS and may
      specifically shed new light on the failure of remyelination in chronic
      demyelinating diseases such as multiple sclerosis.

PMID- 22646083
TI  - Mean platelet volume in patients with increased procalcitonin level.

PMID- 22646085
TI  - Synthesis, characterization, and evaluation of five coordinated copper(II)
      complexes as antibacterial, artificial nuclease, and SOD mimics.
AB  - The copper(II) complexes with ciprofloxacin (CFLH), levofloxacin (LFLH),
      norfloxacin (NFLH), and neutral bidentate ligands have been synthesized and
      characterized. The complexes have been evaluated for their antibacterial activity
      against selective species. Complexes have been also checked for their interacting
      behavior with DNA, and were found to have two different modes of interaction,
      classical and partial intercalation. Tested complexes were found to be better
      antioxidants with their IC(50) values ranging from 0.51 to 0.97 MUM.

PMID- 22646084
TI  - Systematic comprehensive geriatric assessment in elderly patients on chronic
      dialysis: a cross-sectional comparative and feasibility study.
AB  - BACKGROUND: Elderly dialysis patients are prone to disabilities and functional
      decline. This aggravates their last period of life. It would be valuable to be
      able to preserve daily function and quality of life. Identification of domains
      requiring additional attention is not common practice in standard care.
      Therefore, we performed a systematic Comprehensive Geriatric Assessment (CGA) to
      assess physical and psychosocial function and tested its feasibility in daily
      practice. The CGA is used more frequently in the assessment of elderly cancer
      patients, and we therefore compared the outcomes to this group. METHODS: A cross
      sectional, multicenter study, between June 1st and September 31st, 2009, in four
      Dutch outpatient dialysis units. Fifty patients aged 65 years or above who
      received dialysis because of end-stage renal disease (ESRD) were randomly
      included. We assessed the CGA during a systematic interview with patients and
      their caregivers. The cancer patients had had a similar CGA in an earlier study.
      We compared prevalences between groups. RESULTS: In the dialysis population
      (68.0% 75 years or above, 76.6% on haemodialysis) caregivers often observed
      behavioral changes, such as deviant eating habits (34.0%) and irritability
      (27.7%). In 84.4%, caregivers felt overburdened by the situation of their family
      member. Somatic and psychosocial conditions were frequently found (polypharmacy
      (94.6%), depression (24.5%)) and prevalence of most geriatric conditions was
      comparable to those in elderly cancer patients. CONCLUSIONS: Geriatric conditions
      were highly prevalent among elderly dialysis patients and prevalences were
      comparable in both populations. The CGA proved feasible for recognition of these
      conditions and of overburdened caregivers. This could prevent further functional
      decline and preserve quality of life.

PMID- 22646086
TI  - Effects of halides on reaction of nucleosides with ozone.
AB  - Ozone (O(3)), a major component of photochemical oxidants, is used recently as a
      deodorizer in living spaces. It has been reported that O(3) can directly react
      with DNA, causing mutagenesis in human cells and carcinogenesis in mice. However,
      little is known about the effects of coexistent ions in the reaction of O(3). In
      the present study, we analyzed the effects of halides on the reaction of O(3)
      with nucleosides using reversed-phase high-performance liquid chromatography with
      ultraviolet detection. When aqueous O(3) solution was added to a nucleoside
      mixture in potassium phosphate buffer (pH 7.3), the nucleosides were consumed
      with the following decreasing order of importance: dGuo > Thd > dCyd > dAdo. The
      effects of addition of fluoride and chloride in the system were slight. Bromide
      suppressed the reactions of dGuo, Thd, and dAdo but enhanced the reaction of
      dCyd. The major products were 5-hydroxy-2'-deoxycytidine, 5-bromo-2'
      deoxycytidine, and 8-bromo-2'-deoxyguanosine. The time course and pH dependence
      of the product yield indicated formation of hypobromous acid as the reactive
      agent. Iodide suppressed all the reactions effectively. The results suggest that
      bromide may alter the mutation spectrum by O(3) in humans.

PMID- 22646087
TI  - Antiproliferative activity of kinetin riboside on HCT-15 colon cancer cell line.
AB  - Cytokinins and cytokinin nucleosides are purine derivatives with potential
      anticancer activity both in vitro and in vivo. N(6)-furfuryladenosine (kinetin
      riboside, KR) displays antiproliferative and apoptogenic activity against various
      human cancer cell lines and has recently been shown to suppress tumor growth in
      murine xenograft models of human leukemia and melanoma. In this study, we
      demonstrate that KR is able to inhibit the proliferation in HCT-15 human colon
      cancer cells in a dose-dependent manner with a concentration of 2.5 MUM, which
      causes 50% inhibition of cell viability. The cell cycle analysis by flow
      cytometry showed that KR arrested cell cycle progression in the S Phase by
      blocking through G(2)/M and G(0)/G(1) phase in HCT-15 colon cells. Moreover,
      suppression of clonogenic activity occurs after exposure to KR at a concentration
      of 2.5 MUM for HCT-15.

PMID- 22646088
TI  - Synthesis and cytotoxic activity of novel 5-substituted-1-(beta-L
      arabinofuranosyl) pyrimidine nucleosides.
AB  - A series of new 5-halogeno-1-(beta-L-arabinofuranosyl)uracils and their cytosine
      analogues were synthesized by halogenation of ara-L-uridine and ara-L-cytidine,
      respectively. The 5-(2-thienyl) and 5-halogenothienyl derivatives of both series
      were also prepared in excellent yields by Stille coupling followed by
      halogenation. All of these syntheses were based on benzoyl-protected derivatives.
      In vitro cytotoxicity experiments carried out using L1210 mouse leukemia cells
      showed that 5-(2-thienyl)-ara-L-uridine was the most potent compound of the new
      compounds; the majority of the analogues were not effective up to 200 MUM
      concentrations.

PMID- 22646090
TI  - MergeAlign: improving multiple sequence alignment performance by dynamic
      reconstruction of consensus multiple sequence alignments.
AB  - BACKGROUND: The generation of multiple sequence alignments (MSAs) is a crucial
      step for many bioinformatic analyses. Thus improving MSA accuracy and identifying
      potential errors in MSAs is important for a wide range of post-genomic research.
      We present a novel method called MergeAlign which constructs consensus MSAs from
      multiple independent MSAs and assigns an alignment precision score to each
      column. RESULTS: Using conventional benchmark tests we demonstrate that on
      average MergeAlign MSAs are more accurate than MSAs generated using any single
      matrix of sequence substitution. We show that MergeAlign column scores are
      related to alignment precision and hence provide an ab initio method of
      estimating alignment precision in the absence of curated reference MSAs. Using
      two novel and independent alignment performance tests that utilise a large set of
      orthologous gene families we demonstrate that increasing MSA performance leads to
      an increase in the performance of downstream phylogenetic analyses. CONCLUSION:
      Using multiple tests of alignment performance we demonstrate that this novel
      method has broad general application in biological research.

PMID- 22646091
TI  - Crystal structures of Trypanosoma cruzi UDP-galactopyranose mutase implicate
      flexibility of the histidine loop in enzyme activation.
AB  - Chagas disease is a neglected tropical disease caused by the protozoan parasite
      Trypanosoma cruzi. Here we report crystal structures of the galactofuranose
      biosynthetic enzyme UDP-galactopyranose mutase (UGM) from T. cruzi, which are the
      first structures of this enzyme from a protozoan parasite. UGM is an attractive
      target for drug design because galactofuranose is absent in humans but is an
      essential component of key glycoproteins and glycolipids in trypanosomatids.
      Analysis of the enzyme-UDP noncovalent interactions and sequence alignments
      suggests that substrate recognition is exquisitely conserved among eukaryotic
      UGMs and distinct from that of bacterial UGMs. This observation has implications
      for inhibitor design. Activation of the enzyme via reduction of the FAD induces
      profound conformational changes, including a 2.3 A movement of the histidine loop
      (Gly60-Gly61-His62), rotation and protonation of the imidazole of His62, and
      cooperative movement of residues located on the si face of the FAD.
      Interestingly, these changes are substantially different from those described for
      Aspergillus fumigatus UGM, which is 45% identical to T. cruzi UGM. The importance
      of Gly61 and His62 for enzymatic activity was studied with the site-directed
      mutant enzymes G61A, G61P, and H62A. These mutations lower the catalytic
      efficiency by factors of 10-50, primarily by decreasing k(cat). Considered
      together, the structural, kinetic, and sequence data suggest that the middle Gly
      of the histidine loop imparts flexibility that is essential for activation of
      eukaryotic UGMs. Our results provide new information about UGM biochemistry and
      suggest a unified strategy for designing inhibitors of UGMs from the eukaryotic
      pathogens.

PMID- 22646092
TI  - Insights on biology and pathology of HIF-1alpha/-2alpha, TGFbeta/BMP, Wnt/beta
      catenin, and NF-kappaB pathways in osteoarthritis.
AB  - Osteoarthritis (OA) constitutes a major health problem. Different signaling
      pathways are involved that impair homeostasis, but the cross-talk between them
      (although well investigated and partly understood), remains unclear. HIF-1alpha
      promotes chondrocyte differentiation and survival, while HIF-2alpha coactivates
      with beta-catenin and NF-kappaB pathways to promote chondrocyte apoptosis and
      endochondral ossification. Depending on the ALK1/ALK5 ratio in chondrocytes, the
      TGFbeta pathway can play an anabolic or catabolic role. TGFbeta1 can activate the
      beta-catenin signaling pathway via ALK5, Smad3, PI3K, and PKA pathways. The
      mediator Axins balance TGF-beta and Wnt/beta-catenin signaling during chondrocyte
      proliferation and maturation. However, the biological functions of Wnt/beta
      catenin signaling are still controversial. Both excessive and insufficient beta
      catenin levels may impair the homeostasis of articular chondrocytes by enhancing
      pathological maturation and apoptosis, respectively; loss- and gain-of-functions
      of beta-catenin cause apoptosis at the center of the joint and chondrocyte
      maturation at the periphery, depending on the vascularity. The NF-kappaB
      transcription factor can be triggered by a host of stress-related stimuli
      including pro-inflammatory cytokines. The recent discovery of functional cross
      regulation between these pathways has shown complex roles for HIF-1alpha/HIF
      2alpha, TGFbeta/BMP, Wnt/beta-catenin, and NF-kappaB signaling pathways in the
      pathogenesis of OA. This has important implications for potential therapeutic
      agents directed at these pathways.  This review attempts to cover the literature
      of the past three years dealing with the biology and pathology of the HIF-1alpha/
      2alpha, TGFbeta/BMP, Wnt/beta-catenin, and NF-kappaB/cytokines signaling pathways
      in OA.

PMID- 22646093
TI  - A homeobox protein Phx1 regulates long-term survival and meiotic sporulation in
      Schizosaccharomyces pombe.
AB  - BACKGROUND: In the fission yeast Schizosaccharomyces pombe, the phx1+ (pombe
      homeobox) gene was initially isolated as a multi-copy suppressor of lysine
      auxotrophy caused by depletion of copper/zinc-containing superoxide dismutase
      (CuZn-SOD). Overproduction of Phx1 increased the synthesis of homocitrate
      synthase, the first enzyme in lysine biosynthetic pathway, which is labile to
      oxidative stress. Phx1 has a well conserved DNA-binding domain called homeodomain
      at the N-terminal region and is predicted to be a transcription factor in S.
      pombe. However, its role has not been revealed in further detail. Here we
      examined its expression pattern and the phenotype of its null mutant to get clues
      on its function. RESULTS: Fluorescence from the Phx1-GFP expressed from a
      chromosomal fusion gene demonstrated that it is localized primarily in the
      nucleus, and is distinctly visible during the stationary phase. When we replaced
      the N-terminal homeobox domain of Phx1 with the DNA binding domain of Pap1, a
      well-characterized transcription factor, the chimeric protein caused the
      elevation of transcripts from Pap1-dependent genes such as ctt1+ and trr1+,
      suggesting that Phx1 possesses transcriptional activating activity when bound to
      DNA. The amount of phx1+ transcripts sharply increased as cells entered the
      stationary phase and was maintained at high level throughout the stationary
      phase. Nutrient shift down to low nitrogen or carbon sources caused phx1+
      induction during the exponential phase, suggesting that cells need Phx1 for
      maintenance function during nutrient starvation. The Deltaphx1 null mutant showed
      decreased viability in long-term culture, whereas overproduction of Phx1
      increased viability. Decrease in long-term survival was also observed for
      Deltaphx1 under N- or C-starved conditions. In addition, Deltaphx1 mutant was
      more sensitive to various oxidants and heat shock. When we examined sporulation
      of the Deltaphx1/Deltaphx1 diploid strain, significant decrease in the formation
      of meiotic spores was observed. CONCLUSIONS: Phx1 is a transcriptional regulator
      whose synthesis is elevated during stationary phase and by nutrient starvation in
      S. pombe. It supports long-term survival and stress tolerance against oxidation
      and heat, and plays a key role in the formation of meiotic spores.

PMID- 22646094
TI  - Effects of ethanol and dimethyl sulfoxide on the molecular organization of H2O as
      probed by 1-propanol.
AB  - We characterized the effects of ethanol (ET) and dimethyl sulfoxide (DMSO) on
      H(2)O within a limited H(2)O-rich region by the 1-propanol (1P)-probing
      methodology developed by us earlier. The results are displayed on a two
      dimensional map with twin coordinates: one pertaining to hydrophobicity and the
      other to hydrophilicity. The locus of ET on this map was at a point in between
      methanol (ME) and 2-propanol (2P) as expected from our earlier findings by
      thermodynamic studies. That for DMSO, however, was surprisingly more hydrophilic
      than ME. Similar to N-methyl groups discussed recently (J. Phys. Chem. B 2011,
      115, 2995), it was argued that the methyl groups attached to the S atom are made
      susceptible for direct hydrogen bonding to the surrounding H(2)O molecules due
      possibly to the electronegativity of the S atom. In view of these findings, we
      suggest caution to be exercised for the conventional general trend of taking any
      methyl groups to be "hydrophobic."

PMID- 22646095
TI  - Women show a closer association between educational level and hypertension or
      diabetes mellitus than males: a secondary analysis from the Austrian HIS.
AB  - BACKGROUND: Lifestyle diseases and cardiovascular complications are dramatically
      increasing, but little is known about the impact of educational level and health
      behaviour in men and women in different populations. Therefore, we aimed to
      investigate the association between educational level (EL) and self-reported
      chronic diseases and health behaviour in both sexes. METHODS: Data were derived
      from the Austrian Health Interview Surveys 2006/2007, which includes 13 558
      persons (50.9% females). The associations between EL and the risk of obesity,
      hypertension, diabetes, myocardial infarction, stroke and anxiety disorders or
      depression, nutrition, exercise, and smoking were evaluated. University education
      served as the reference category (EL4), the lowest educational level was required
      schooling only (EL0). RESULTS: Only among women did the risk for diabetes
      mellitus and hypertension increase with decreasing educational level with the
      highest rates for EL0 OR [95% CI] adjusted for age, income, family status and
      lifestyle: 3.7 [1.7-8.0], and 2.5 [1.8-3.5], respectively. Only among the men,
      however, did the risk for stroke increase with decreasing educational level
      adjusted OR for EL0: 8.5 [1.7-42.7]. For anthropometric measures and lifestyle
      factors in both sexes the risk increased with decreasing EL. CONCLUSION: EL
      affects lifestyle, overweight and obesity in both sexes. The apparent sex
      specific differences in the association between the prevalence of some chronic
      disease with EL call for further investigation.

PMID- 22646096
TI  - Psychological partner violence and women's vulnerability to depression, stress,
      and anxiety.
AB  - Psychological partner violence is a considerable problem, despite its invisible
      outcomes on victims' physical health. Focusing on mental health, the present
      study looked at differences in mental illness, such as depression, stress, and
      anxiety, among victims and non-victims of psychological violence. A convenience
      sample of women (n = 267) visiting health-care centres in refugee camps in Jordan
      provided data about their experiences of psychological violence and their mental
      health status. The results indicated that, compared to their non-victimized
      counterparts, women reporting psychological violence had significantly higher
      mean scores of depression (t = -4.92), stress (t = -3.73), and anxiety (t = 
      4.22), with P < 0.0001 for all results. It was suggested that factors that have
      significant roles in determining poor mental health status included victims' low
      self-esteem; poor socioeconomic profile, in terms of education level and income;
      and responsibilities associated with child and family requirements. The impacts
      of these factors on victims' mental health status are discussed.

PMID- 22646097
TI  - Mesoporous silica nanoparticles capped with disulfide-linked PEG gatekeepers for
      glutathione-mediated controlled release.
AB  - Hybrid mesoporous silica nanoparticles (MSNs), which were synthesized using the
      co-condensation method and engineered with unique redox-responsive gatekeepers,
      were developed for studying the glutathione-mediated controlled release. These
      hybrid nanoparticles constitute a mesoporous silica core that can accommodate the
      guests (i.e., drug, dye) and the PEG shell that can be connected with the core
      via disulfide-linker. Interestingly, the PEG shell can be selectively detached
      from the inner core at tumor-relevant glutathione (GSH) levels and facilitate the
      release of the encapsulated guests at a controlled manner. The structure of the
      resulting hybrid nanoparticles (MSNs-SS-mPEG) was comprehensively characterized
      by transmission electron microscopy (TEM), Fourier transform infrared
      spectroscopy (FTIR), powder X-ray diffraction (XRD), and nitrogen
      adsorption/desorption isotherms analysis. The disulfide-linked PEG chains
      anchored on MSNs could serve as efficient gatekeepers to control the on-off of
      the pores. Compared with no GSH, fluorescein dye as the model drug loaded into
      MSNs showed rapid release in 10 mM GSH, indicating the accelerated release after
      the opening of the pores regulated by GSH. Confocal microscopy images showed a
      clear evidence of the dye-loaded MSNs-SS-mPEG nanoparticles endocytosis into MCF
      7 cells and releasing guest molecules from the pore inside cells. Moreover, in
      vitro cell viability test using MTT assay indicated that MSNs-SS-mPEG
      nanoparticles had no obvious cytotoxicity. These results indicate that MSNs-SS
      mPEG nanoparticles can be used in the biomedical field. 

PMID- 22646098
TI  - Ultrahigh nanoparticle stability against salt, pH, and solvent with retained
      surface accessibility via depletion stabilization.
AB  - For many applications, it is desirable to stabilize colloids over a wide range of
      buffer conditions while still retaining surface accessibility for adsorption and
      reaction. Commonly used charge or steric stabilization cannot achieve this goal
      since the former is sensitive to salt and the latter blocks the particle surface.
      We use depletion stabilization in the presence of high molecular weight
      polyethylene glycol (PEG) to stabilize a diverse range of nanomaterials,
      including gold nanoparticles (from 10 to 100 nm), graphene oxide, quantum dots,
      silica nanoparticles, and liposomes in the presence of Mg(2+) (>1.6 M), heavy
      metal ions, extreme pH (pH 1-13), organic solvents, and adsorbed nucleosides and
      drugs. At the same time, the particle surface remains accessible for adsorption
      of both small molecules and macromolecules. Based on this study, high loading of
      thiolated DNA was achieved in one step with just 2% PEG 20,000 in 2 h.

PMID- 22646100
TI  - TSCA's Impact on Society and Chemical Industry.

PMID- 22646099
TI  - Sirrine.

PMID- 22646102
TI  - Normandeau associates, inc.

PMID- 22646103
TI  - Letters.

PMID- 22646104
TI  - William ruckleshaus and the u.s. EPA.

PMID- 22646105
TI  - International.

PMID- 22646106
TI  - Washington.

PMID- 22646108
TI  - Science.

PMID- 22646107
TI  - States.

PMID- 22646110
TI  - Technology.

PMID- 22646109
TI  - Industry.

PMID- 22646111
TI  - Risks: How to get more science in assessments.

PMID- 22646113
TI  - Alcohol fuels from biomass.

PMID- 22646112
TI  - A legislative proposal for "SENSE".

PMID- 22646114
TI  - Products.

PMID- 22646117
TI  - Classified section.

PMID- 22646116
TI  - Courses.

PMID- 22646119
TI  - international light inc.

PMID- 22646120
TI  - Climatronics corp.

PMID- 22646121
TI  - Nternational.

PMID- 22646122
TI  - professional consulting services directory.

PMID- 22646124
TI  - Index to the advertisers in this issue.

PMID- 22646125
TI  - Dietary phosphorus in bone health and quality of life.
AB  - Awareness of phosphorus intake is important because both phosphorus deficiency
      and overloading impair bone health and quality of life. Phosphorus consumption is
      increasing in many countries. Most dietary phosphorus is contained in protein
      rich foods such as meat, milk, cheese, poultry, fish, and processed foods that
      contain phosphate-based additives to improve their consistency and appearance.
      Elevation of extracellular phosphorus levels causes endothelial dysfunction and
      medial calcification, which are closely associated with the development of
      cardiovascular disease (CVD). Long-term excessive phosphorus loading, even if it
      does not cause hyperphosphatemia, can be a risk factor for CVD. In
      epidemiological studies, higher levels of phosphorus intake have been associated
      with reduced blood pressure. Interestingly, when examined further, phosphorus
      from dairy products, but not from other sources, was usually associated with
      lower blood pressure. A dietary approach to phosphorus reduction is particularly
      important to prevent bone impairment and CVD in patients with chronic kidney
      disease. In order to improve bone health and quality of life in the general
      population, the impact of phosphorous, including in processed foods, should be
      considered, and measures to indicate the amount of phosphorous in food products
      should be implemented.

PMID- 22646126
TI  - Systematic review and meta-analysis of energy and macronutrient intakes during
      pregnancy in developed countries.
AB  - Research reporting diet during pregnancy in nationally representative samples is
      limited. This review summarizes the dietary intakes of pregnant women in
      developed countries and compares them with national recommendations. A systematic
      search without date limits was conducted. All studies reporting the macronutrient
      intakes of pregnant women were considered, irrespective of design. Two authors
      independently identified the studies to be included and assessed the
      methodological quality. Nutritional adequacy was summarized, with confounding
      factors considered. Meta-analysis data are reported for developed countries
      collectively, by geographical region, and by dietary methodology. Energy and
      macronutrient intakes of pregnant women do not match national recommendations.
      Energy and fiber intakes were consistently below recommendations, while total fat
      and saturated fat intakes were generally above recommendations and carbohydrate
      and polyunsaturated fat intakes were below to borderline low compared with
      recommendations. A mismatch between dietary practices and macronutrient
      recommendations in pregnant women is widespread and not well quantified. The
      implications of these practices are unknown until further research compares
      maternal diet with short-term and long-term maternal and offspring health
      outcomes.

PMID- 22646127
TI  - Dietary aspects of migraine trigger factors.
AB  - The significance of dietary factors as triggers for migraines is controversial,
      and the assessment of this topic is complex and inconclusive. In order to
      evaluate the published evidence on dietary triggers, a critical review of the
      literature was performed by conducting a search for food item descriptors linked
      to migraines in the PubMed and SciELO databases. Reviews and relevant references
      cited within the articles that resulted from the search were also included. Of
      the 45 studies reviewed, 16 were population studies that involved the association
      between migraines and eating habits or the prevalence of related dietary factors;
      12 involved interventions or analyzed observational prospective cohorts; and 17
      were retrospective studies. Approximately 30 dietary triggers were explored in
      total, although only seven of these were addressed experimentally. In the
      prospective studies, patients were instructed to keep a diary; two of these
      studies involved dietary interventions. Conclusions that are based on
      nonpharmacological prophylactic strategies with a scientific basis and that show
      an association between certain dietary factors and the triggering of migraines
      are limited by the lack of prospective studies with clear experimental designs.
      Nevertheless, the high frequency of possible specific dietary triggers validates
      efforts to elucidate the involvement of food-related factors in precipitating
      migraines.

PMID- 22646128
TI  - Niacin: chemical forms, bioavailability, and health effects.
AB  - Elevated low-density lipoprotein cholesterol (LDL-C) has been the main target of
      lipid-altering therapy to reduce cardiovascular risk associated with
      dyslipidemia. Residual cardiovascular risk remains, however, after achievement of
      goal LDL-C levels and is associated in part with other risk markers of
      cardiovascular disease, including low high-density lipoprotein cholesterol (HDL
      C), high lipoprotein a, and hypertriglyceridemia. Niacin is considered a valuable
      agent for therapy to modify high LDL-C as well as low HDL-C, high lipoprotein a,
      and hypertriglyceridemia. The forms of niacin available in the marketplace
      include unbound niacin, or free nicotinic acid (NA); extended-release NA, a form
      of NA that is released gradually over a period of time; inositol hexanicotinate,
      six molecules of NA covalently bonded to one molecule of inositol; and
      nicotinamide, or niacinamide, the amide form of NA, which is readily
      bioavailable. This review is designed to assist healthcare professionals in
      evaluating the form(s) of niacin best suited for a particular therapeutic goal.
      Further, it provides a literature-based evaluation of risk for NA, extended
      release NA, inositol hexanicotinate, and nicotinamide.

PMID- 22646129
TI  - Inorganic nitrate: a major player in the cardiovascular health benefits of
      vegetables?
AB  - Epidemiological evidence suggests a higher consumption of vegetables confers a
      protective effect against the risk of cardiovascular disease. Impaired
      bioavailability of nitric oxide (NO), which is a critical regulator of vascular
      homeostasis, in the vasculature is thought to be a major problem in
      cardiovascular disease. Classically, vascular endothelium is suggested to be the
      sole source of bioactive NO in the vasculature. Emerging literature, however,
      associates the nitrate-nitrite-NO pathway, in which endogenous nitrate undergoes
      reduction to nitrite and then to NO in various tissues, including blood, with the
      production of bioactive NO. Indeed, NO generated from the nitrate-nitrite-NO
      pathway has recently been associated with the maintenance of NO homeostasis in
      the body. Endogenous nitrate originates mostly from NO oxidation in the
      biological milieu and from exposure to dietary nitrate. Consumption of vegetables
      accounts for approximately 80-85% of daily nitrate exposure in humans, thereby
      establishing inorganic nitrate as a promising factor in the cardiovascular health
      benefits of vegetables. At this point in time, however, the benefit : hazard
      ratio of inorganic nitrate and its active metabolite nitrite remains less clear
      and must be studied in prospective controlled studies. This brief review
      discusses the potential role of inorganic dietary nitrate in the cardiovascular
      health benefits of vegetables.

PMID- 22646131
TI  - A zinc(II) phthalocyanine conjugated with an oxaliplatin derivative for dual
      chemo- and photodynamic therapy.
AB  - A novel zinc(II) phthalocyanine substituted with an oxaliplatin derivative via a
      triethylene glycol linker has been synthesized. The two components work in a
      cooperative manner in the antitumor action. The conjugate shows a cytotoxic
      effect in the dark due to the cytostatic oxaliplatin moiety and an enhanced
      cytotoxicity upon illumination due to the photosensitizing phthalocyanine unit
      against the HT29 human colon adenocarcinoma cells. The IC(50) value of the
      conjugate is as low as 0.11 MUM, which is 5-fold lower than that of the reference
      compound without the platinum complex. The high photodynamic activity of the
      conjugate can be attributed to its high cellular uptake and efficiency in
      generating intracellular reactive oxygen species. The conjugate also shows
      preferential localization in the lysosomes of the cells and induces cell death
      mainly through apoptosis.

PMID- 22646132
TI  - Intraventricular rituximab and systemic chemotherapy for treatment of central
      nervous system post-transplant lymphoproliferative disorder after kidney
      transplantation.
AB  - PTLD of the CNS is a rare complication of solid organ transplantation, and there
      are only case reports/series available in the literature. Current literature
      suggests that CNS PTLD carries a worse prognosis than PTLD outside the CNS, and
      most are of B-cell lineage, predominantly monomorphic, and are associated with
      EBV infection. Because this disorder is so rare, there is no standard
      chemotherapy for pediatric patients with CNS PTLD and reported therapies for EBV
      associated CNS PTLD are heterogeneous with mixed results. Since outcomes of CNS
      PTLD are historically poor, we attempted to develop a novel therapeutic treatment
      regimen. Based on a review of the literature and with the help of a
      multidisciplinary team, we created a regimen of chemotherapy that included
      dexamethasone and high-dose methotrexate in addition to intravenous and
      intraventricular Rituximab in two pediatric patients. The intraventricular
      chemotherapy succeeded in shrinking the tumor in both of our patients; however,
      as shown in the second case, the clinical outcome depends on the location of the
      tumor. Systemic and intraventricular therapies hold promise in the management of
      EBV-associated CNS PTLD; however the rarity of this entity prevents the
      development of well-designed studies necessary for the establishment of an
      evidence-based treatment standard.

PMID- 22646134
TI  - Deficits in two versions of a sustained attention test in adolescents with
      cerebral palsy.
AB  - OBJECTIVE: To evaluate sustained attention in adolescents with cerebral palsy
      (CP). CP affects motor control as well as certain cognitive processes such as
      attention, but its influence on the latter remains largely unexplored. METHODS:
      Manual (Experiment 1) and oculomotor (Experiment 2) versions of the Continuous
      Performance Test were performed by adolescents with spastic CP and healthy age
      matched controls (n = 10 per group in each experiment). RESULTS: In both
      experiments, patients with CP showed more omissions and their reaction time was
      more variable than controls. In Experiment 2, patients also showed more
      commissions. This problem was not observed in Experiment 1, possibly because of
      the presence of a hand movement deficit in CP. CONCLUSION: Taken together, the
      results show that sustained attention and inhibition capabilities are affected in
      CP. The present study also proposes that eye movements could constitute an
      interesting alternative for measuring sustained attention when hand movement is
      affected.

PMID- 22646133
TI  - Tioguanine in the treatment of refractory coeliac disease--a single centre
      experience.
AB  - BACKGROUND: Refractory coeliac disease type I is a complicated form of coeliac
      disease characterised by primary or secondary resistance to a gluten-free diet
      with persisting or reoccurring intestinal villous atrophy and symptoms of
      malabsorption. Besides corticosteroids, azathioprine has been advocated for the
      treatment of refractory coeliac disease type I. However, tioguanine (TG) might be
      better tolerated and more efficacious owing to a simpler metabolism towards
      bioactivation. AIM: To evaluate tolerability and effectiveness of the
      nonconventional thiopurine derivative TG in refractory coeliac disease type I.
      METHODS: Refractory coeliac disease type I patients treated with TG between June
      2001 and November 2010 with a follow-up period of at least 1 year were included.
      Adverse events, laboratory values, 6-thioguanine nucleotide concentrations and
      rates of both clinical and histological response were evaluated at baseline and
      during follow-up. RESULTS: Twelve adult refractory coeliac disease type I
      patients were included. The median TG treatment duration was 14 months. Ten
      patients tolerated TG treatment on the long term, whereas two patients withdrew
      treatment due to adverse events. No nodular regenerative hyperplasia of the liver
      was observed. During follow-up clinical and histological response was observed in
      83% and 78%, respectively. Corticosteroid dependency decreased by 50%.
      CONCLUSION: Tioguanine appears to be a convenient drug for the treatment of
      refractory coeliac disease type I based on higher histological and similar
      clinical response rates as compared with historical conventional therapies.

PMID- 22646135
TI  - Chains of evidence, mosaics of data: does estrogen 'cause' breast cancer? How
      would we know?
AB  - There appears to be a broad consensus that estrogen is a cause of breast cancer.
      Proof of cause and effect in clinical medicine requires a different approach for
      an epidemiological exposure (a 'mosaic' approach) than for an infectious agent
      suspected of causing a particular disease (a 'chain of evidence' approach). This
      paper discusses the differences between these two approaches in determining the
      relationship between a risk factor and a disease, and assesses the strength of
      the data linking estrogen with breast cancer. Analysis of existing data,
      including findings from the Women's Health Initiative, finds that all nine of the
      criteria necessary for confirming the epidemiological strength of a risk factor
      are not met in the case of estrogen, raising serious questions about the validity
      of this widespread assumption.

PMID- 22646136
TI  - Prevalence of nonspecific cutaneous vascular lesions and association with
      antiphospholipid antibodies in patients with systemic lupus erythematosus.

PMID- 22646137
TI  - Umbilical cord versus bone marrow-derived mesenchymal stromal cells.

PMID- 22646138
TI  - Psychological well-being using the 12-item General Health Questionnaire (GHQ12)
      and age in Japanese working men.

PMID- 22646139
TI  - On the molecular mechanism of stabilization of proteins by cosolvents: role of
      Lifshitz electrodynamic forces.
AB  - Several ionic and nonionic additives are known to affect structural stability of
      proteins in aqueous solutions. At a fundamental level, the mechanism of
      stabilization or destabilization of proteins by cosolvents must be related to
      three-body interactions between the protein, additive, and the water medium. In
      this study, the role of the Lifshitz-van der Waals electrodynamic interaction
      between various additives (sucrose, glycerol, urea, poly(ethylene glycol)-200,
      betaine, taurine, proline, and valine) and bovine serum albumin (BSA) in water
      medium was examined. The electrodynamic interaction energy was attractive for all
      of the additives studied here when both far ultraviolet and infrared relaxations
      of the additives were included in their dielectric susceptibility
      representations. However, when only the infrared contribution was included for
      structure stabilizers and both far ultraviolet and infrared contributions for the
      structure destabilizers, the resulting electrodynamic interaction energy (E/kT)
      followed the structure stabilizing and/or destabilizing behavior of the
      additives; that is, the interaction was attractive for urea and PEG200 (structure
      destabilizers), whereas it was repulsive for sucrose, glycerol, betaine, taurine,
      alanine, valine, and proline (structure stabilizers). The electrodynamic
      interaction energy E/kT at any given surface-to-surface separation distance
      between the additives and BSA was positively correlated (r(2) = 0.92) with the
      experimental thermal denaturation temperature (T(d)) of BSA in 1 M solutions of
      the additives. These analyses provided a mechanistic basis for the experimental
      observations of exclusion of the structure-stabilizing additives from the protein
      water interface and binding of the structure-destabilizing additives to the
      protein surface. The role of water structure in the three-body electrodynamic
      interaction is discussed. It is hypothesized that in the case of additives that
      enhance water structure the hydration shells formed around the additives
      effectively dampen the contribution of ultraviolet frequencies to the dielectric
      susceptibility of the additives and thus impart repulsive electrodyanamic
      interaction between the additive and the protein, whereas the opposite occurs in
      the case of additives that breakdown the hydrogen-bonded structure of water.

PMID- 22646140
TI  - Effect of intravenous proton pump inhibitor regimens and timing of endoscopy on
      clinical outcomes of peptic ulcer bleeding.
AB  - BACKGROUND AND AIM: The most effective schedule of proton pump inhibitor (PPI)
      administration and the optimal timing of endoscopy in acute peptic ulcer bleeding
      remain uncertain. The aim of this study was to determine the most efficient PPI
      regimen and optimal timing of endoscopy. METHODS:   Consecutive patients with
      suspected bleeding peptic ulcers were enrolled and randomized to receive either a
      standard regimen or a high-dose intensive intravenous regimen. Only patients with
      bleeding peptic ulcers diagnosed at initial endoscopy continued the study. High
      risk patients received endoscopic hemostasis. The primary outcome measure of
      recurrent bleeding was compared between the two dosage regimens and between early
      and late endoscopy. Secondary outcome measures compared included need for
      endoscopic treatment, blood transfusion, hospital stay, surgery and mortality.
      RESULTS: A total of 875 patients completed the study. Recurrent bleeding occurred
      in 11.0% in the standard regimen group, statistically higher than that in the
      intensive regimen group (6.4%, P=0.02). Mean units of blood transfused and
      duration of hospital stay were also higher in the standard regimen group (P<0.001
      for each compared to intensive regimen group). However, no significant
      differences were noted between the two groups in the need for endoscopic
      hemostasis, need for surgery, and mortality. Recurrence of bleeding was similar
      between the early and late endoscopy groups. Units of blood transfused and length
      of hospital stay were both significantly reduced with early endoscopy.
      CONCLUSION: High-dose PPI infusion is more efficacious in reducing rebleeding
      rate, blood transfusion requirements and hospital stay. Early endoscopy is safe
      and more effective than late endoscopy.

PMID- 22646142
TI  - Antigen-matched red blood cell transfusions for patients with sickle cell disease
      at The Johns Hopkins Hospital.

PMID- 22646141
TI  - Caffeic acid phenethyl ester prevents detrimental effects of remote ischemia
      reperfusion injury on healing of colonic anastomoses.
AB  - PURPOSE: We aimed to investigate whether caffeic acid phenethyl ester (CAPE)
      prevents detrimental systemic effects of intestinal ischemia-reperfusion (IR)
      injury on colonic anastomotic wound healing. METHODS: This experimental study was
      conducted on 48 male Wistar albino rats. The rats were randomly allocated into
      four groups and a left colonic anastomosis was performed in all rats: (i) sham
      operated group (n = 12), laparatomy without intestinal IR injury; (ii) sham +
      CAPE group (n = 12), identical to Group 1 except for CAPE treatment (10 MUmol/kg,
      intravenously); (iii) intestinal IR group (n = 12), 60 min of superior mesenteric
      ischemia followed by reperfusion; and (iv) IR + CAPE-treated group (n = 12) (10
      MUmol/kg, intravenously, 30 min before the construction of colonic anastomosis).
      On the postoperative day 7, the rats were subjected to relaparotomy for in vivo
      measurement of the colonic anastomotic bursting pressure. A colonic segment
      including the anastomotic site was resected for histopathological evaluation and
      biochemical analyses. The plasma proinflammatory cytokine levels were measured.
      Body weight changes were examined. RESULTS: CAPE treatment significantly
      increased colonic anastomotic bursting pressures, and colonic anastomotic tissue
      hydroxyproline contents and antioxidant parameters (p < .05), and significantly
      decreased oxidative stress markers in colonic anastomotic tissues and plasma
      proinflammatory cytokine levels (p < .05). Histopathological scores were
      significantly better due to CAPE administration (p < .05). CONCLUSIONS: This
      study clearly showed that CAPE treatment prevented the delaying effects of remote
      IR injury on colonic anastomotic wound healing. Further clinical studies are
      required to determine whether CAPE has a useful role in the enhancement of
      gastrointestinal anastomotic wound healing during particular surgeries in which
      IR-induced organ injury occurs.

PMID- 22646143
TI  - Directed blood donor program decreases donor exposure for children with sickle
      cell disease requiring chronic transfusion.
AB  - In children with sickle cell disease (SCD), primary and secondary prevention of
      strokes require indefinite regular blood transfusion therapy. The risks
      associated with repeated transfusions include alloimmunization and increased
      donor exposure. The Charles Drew Program is a directed blood donor program
      designed to lower donor exposure, decreasing the associated complications of
      transfusion; however, no evidence exists demonstrating the magnitude of the
      benefit to the recipient. Further, the use of extended red blood cell (RBC)
      antigen matching for C, E, and K has been well documented in a clinical trial
      setting but not extensively evaluated in a standard care setting. The goal of
      this study is to assess the effectiveness in reducing alloimmunization when
      matching for C, E, and K and the magnitude of the decrease in donor exposure in a
      directed blood donor program. The rate of alloimmunization and reduction of donor
      exposure were determined during the course of 1 year in a cohort of children with
      SCD who received regular directed donor blood transfusions. A total of 24
      recipients were in the program, 16 females and 8 males, 4 to 20 years of age.
      During 2008, alloimmunization was 0 percent and donor exposure was reduced by 20
      percent, compared with usual care. Extended RBC antigen matching has the same
      benefit as in a clinical trial setting for patients with SCD receiving blood
      transfusion therapy. Despite significant effort, we only achieved a modest
      decrease in donor exposure and cannot determine the immediate benefit of a
      directed blood donor program.

PMID- 22646144
TI  - Transfusion protocol for patients with sickle hemoglobinopathies at Children's
      National Medical Center.

PMID- 22646145
TI  - Transfusions for patients with sickle cell disease at Children's Hospital Boston.

PMID- 22646146
TI  - The prevention and management of alloimmunization in sickle cell disease: the
      benefit of extended phenotypic matching of red blood cells.

PMID- 22646147
TI  - Transfusion practices for patients with sickle cell disease at major academic
      medical centers participating in the Atlanta Sickle Cell Consortium.
AB  - The Atlanta Sickle Cell Consortium represents more than 2600 pediatric and adult
      patients with sickle cell disease (SCD) in the metropolitan Atlanta, Georgia,
      area receiving care at four major locations, each providing comprehensive care 24
      hours a day, 7 days a week. Both transfusion services that support these sites
      use two levels of prospective phenotype matching to decrease the rates of
      alloimmunization. Although exact rates are unknown and are currently under
      investigation, alloimmunization occurs infrequently with the exception of
      chronically transfused SCD patients, who represent the minority of active SCD
      patients. With increasing availability, red blood cell genotyping will be used in
      the near future both for determination of predicted patient phenotypes and for
      provision of genotypically matched donor units.

PMID- 22646148
TI  - Transfusion practices for patients with sickle cell disease at the Children's
      Hospital of Philadelphia.

PMID- 22646149
TI  - Phylogeography of Asian wild rice, Oryza rufipogon: a genome-wide view.
AB  - Asian wild rice (Oryza rufipogon) that ranges widely across the eastern and
      southern part of Asia is recognized as the direct ancestor of cultivated Asian
      rice (O. sativa). Studies of the geographic structure of O. rufipogon, based on
      chloroplast and low-copy nuclear markers, reveal a possible phylogeographic
      signal of subdivision in O. rufipogon. However, this signal of geographic
      differentiation is not consistently observed among different markers and studies,
      with often conflicting results. To more precisely characterize the phylogeography
      of O. rufipogon populations, a genome-wide survey of unlinked markers,
      intensively sampled from across the entire range of O. rufipogon is critical. In
      this study, we surveyed sequence variation at 42 genome-wide sequence tagged
      sites (STS) in 108 O. rufipogon accessions from throughout the native range of
      the species. Using Bayesian clustering, principal component analysis and amova,
      we conclude that there are two genetically distinct O. rufipogon groups, Ruf-I
      and Ruf-II. The two groups exhibit a clinal variation pattern generally from
      north-east to south-west. Different from many earlier studies, Ruf-I, which is
      found mainly in China and the Indochinese Peninsula, shows genetic similarity
      with one major cultivated rice variety, O. satvia indica, whereas Ruf-II, mainly
      from South Asia and the Indochinese Peninsula, is not found to be closely related
      to cultivated rice varieties. The other major cultivated rice variety, O. sativa
      japonica, is not found to be similar to either O. rufipogon groups. Our results
      support the hypothesis of a single origin of the domesticated O. sativa in China.
      The possible role of palaeoclimate, introgression and migration-drift balance in
      creating this clinal variation pattern is also discussed.

PMID- 22646151
TI  - Curvature changes of bilayer membranes studied by computer simulations.
AB  - The deformation behaviors and corresponding curvature changes of bilayer
      membranes composed of amphiphiles are of biological importance and have potential
      industrial applications. Here, we study the curvature changes of bilayer
      membranes under the area-difference and spontaneous curvature effects with
      dissipative particle dynamics. By varying the relative quantity of the
      amphiphiles in two monolayers or the head-head interaction between the
      amphiphiles within each monolayer, rich morphological responses of the membranes
      are obtained. We find that some important factors such as the ability of
      amphiphiles to change their configurations in different membrane (crowded or
      sparse) environments and the coupling between the two monolayers, which are not
      included in the theoretical models, actually affect the deformation behavior of
      the membrane. Furthermore, the relationship between membrane deformation and
      fission (such as the transition from budding to scission of the bilayer) is also
      discussed, which is helpful in deeply understanding the fission event of the cell
      membrane.

PMID- 22646150
TI  - A closer look at the spectroscopic properties of possible reaction intermediates
      in wild-type and mutant (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase.
AB  - (E)-4-Hydroxy-3-methylbut-2-enyl diphosphate reductase (IspH or LytB) catalyzes
      the terminal step of the MEP/DOXP pathway where it converts (E)-4-hydroxy-3
      methylbut-2-enyl diphosphate (HMBPP) into the two products, isopentenyl
      diphosphate and dimethylallyl diphosphate. The reaction involves the reductive
      elimination of the C4 hydroxyl group, using a total of two electrons. Here we
      show that the active form of IspH contains a [4Fe-4S] cluster and not the [3Fe
      4S] form. Our studies show that the cluster is the direct electron source for the
      reaction and that a reaction intermediate is bound directly to the cluster. This
      active form has been trapped in a state, dubbed FeS(A), that was detected by
      electron paramagnetic resonance (EPR) spectroscopy when one-electron-reduced IspH
      was incubated with HMBPP. In addition, three mutants of IspH have been prepared
      and studied, His42, His124, and Glu126 (Aquifex aeolicus numbering), with
      particular attention paid to the effects on the cluster properties and possible
      reaction intermediates. None of the mutants significantly affected the properties
      of the [4Fe-4S](+) cluster, but different effects were observed when one-electron
      reduced forms were incubated with HMBPP. Replacing His42 led to an increased K(M)
      value and a much lower catalytic efficiency, confirming the role of this residue
      in substrate binding. Replacing the His124 also resulted in a lower catalytic
      efficiency. In this case, however, the enzyme showed the loss of the [4Fe-4S](+)
      EPR signal upon addition of HMBPP without the subsequent formation of the FeS(A)
      signal. Instead, a radical-type signal was observed in some of the samples,
      indicating that this residue plays a role in the correct positioning of the
      substrate. The incorrect orientation in the mutant leads to the formation of
      substrate-based radicals instead of the cluster-bound intermediate complex
      FeS(A). Replacing the Glu126 also resulted in a lower catalytic efficiency, with
      yet a third type of EPR signal being detected upon incubation with HMBPP. (31)P
      and (2)H ENDOR measurements of the FeS(A) species incubated with regular and (2)H
      C4-labeled HMBPP reveal that the substrate binds to the enzyme in the proximity
      of the active-site cluster with C4 adjacent to the site of linkage between the
      FeS cluster and HMBPP. Comparison of the spectroscopic properties of this
      intermediate to those of intermediates detected in (E)-4-hydroxy-3-methylbut-2
      enyl diphosphate synthase and ferredoxin:thioredoxin reductase suggests that
      HMBPP binds to the FeS cluster via its hydroxyl group instead of a side-on
      binding as previously proposed for the species detected in the inactive Glu126
      variant. Consequences for the IspH reaction mechanism are discussed.

PMID- 22646152
TI  - Progress in structure-based drug design against influenza A virus.
AB  - INTRODUCTION: The 2009-H1N1 influenza pandemic has prompted new global efforts to
      develop new drugs and drug design techniques to combat influenza viruses. While
      there have been a number of attempts to provide drugs to treat influenza, drug
      resistance has been a major problem with only four drugs currently approved by
      the FDA for its treatment. AREAS COVERED: In this review, the drug-resistant
      problem of influenza A viruses is discussed and summarized. The article also
      introduces the experimental and computational structures of drug targeting
      proteins, neuraminidases, and of the M2 proton channel. Furthermore, the article
      illustrates the latest drug candidates and techniques of computer-aided drug
      design with examples of their application, including virtual in silico screening
      and scoring, AutoDock and evolutionary technique AutoGrow. EXPERT OPINION:
      Structure-based drug design is the inventive process for finding new drugs based
      on the structural knowledge of the biological target. Computer-aided drug design
      strategies and techniques will make drug discovery more effective and economical.
      It is anticipated that the recent advances in structure-based drug design
      techniques will greatly help scientists to develop more powerful and specific
      drugs to fight the next generation of influenza viruses.

PMID- 22646153
TI  - Update on apelin peptides as putative targets for cardiovascular drug discovery.
AB  - INTRODUCTION: The physiological importance of GPCR/ligand pathways is highlighted
      by the fact that numerous pathologies are attributed to their signaling
      dysfunction. Over 50% of the pharmaceutical drugs currently used to treat human
      disease are based on compounds that interact with GPCRs. Apelin/APJ constitutes a
      novel endogenous peptide/GPCR system proposed to be involved in a wide range of
      physiological functions. Early evidence suggests that apelin/APJ may hold promise
      as a target for development of novel therapeutic agents which may counteract a
      number of pathologies including cardiovascular disease. Despite advances in
      treatment of cardiovascular disease, incidence, prevalence, morbidity and
      economic costs remain high necessitating the development of new treatment
      paradigms. AREAS COVERED: This review summarizes apelin/APJ structure,
      distribution and regulation; presents evidence for a role of apelin in
      pressure/volume homeostasis and in the pathophysiology of cardiovascular disease;
      summarizes data on beneficial effects of apelin in preclinical, animal models of
      cardiovascular disease and measurement of plasma levels of apelin across the full
      spectrum of cardiovascular disease in humans; and notes the first studies
      describing bioactivity of apelin peptides in human healthy volunteers and
      patients with heart failure. EXPERT OPINION: More clarity is needed on the
      precise physiological/pathophysiological role of the apelin/APJ system in human
      health and disease. Nonetheless, preclinical studies and initial studies in
      humans show that APJ antagonism may represent a novel therapeutic target for
      patients with cardiovascular disease. Development of appropriately validated
      assays for apelin will clarify circulating levels of the peptide in health and
      disease. Development of suitable agonists/antagonists will pave the way for much
      needed future studies essential for advancing this promising field of drug
      discovery.

PMID- 22646154
TI  - Fluorescence lifetime assays: current advances and applications in drug
      discovery.
AB  - INTRODUCTION: Fluorescence lifetime assays complement the portfolio of
      established assay formats available in drug discovery, particularly with the
      recent advances in microplate readers and the commercial availability of novel
      fluorescent labels. Fluorescence lifetime assists in lowering complexity of
      compound screening assays, affording a modular, toolbox-like approach to assay
      development and yielding robust homogeneous assays. AREAS COVERED: To date,
      materials and procedures have been reported for biochemical assays on proteases,
      as well as on protein kinases and phosphatases. This article gives an overview of
      two assay families, distinguished by the origin of the fluorescence signal
      modulation. EXPERT OPINION: The pharmaceutical industry demands techniques with a
      robust, integrated compound profiling process and short turnaround times.
      Fluorescence lifetime assays have already helped the drug discovery field, in
      this sense, by enhancing productivity during the hit-to-lead and lead
      optimization phases. Future work will focus on covering other biochemical
      molecular modifications by investigating the detailed photo-physical mechanisms
      underlying the fluorescence signal.

PMID- 22646155
TI  - The anti-mitochondrial antifungal assay for the discovery and development of new
      drugs.
AB  - INTRODUCTION: New targets and drugs are constantly searched for to effectively
      combat fungal infections and diseases such as cancer. Mitochondria, as the main
      powerhouses of eukaryotic cells, must be regarded as important targets for the
      development of new therapies. This has lead to the development of a fungal assay
      that shows potential in the selection of new antifungal and anticancer drugs as
      well as the identification of compounds that are toxic to human mitochondria.
      AREAS COVERED: In this review the authors discuss the development of a potential
      method of drug discovery that targets mitochondrial function. The authors cover
      the application of new nanotechnology as well as fungal systematic research where
      the link between fungal fruiting structures, cell growth, increased mitochondrial
      activity and susceptibility to a variety of anti-mitochondrial drugs is assessed.
      EXPERT OPINION: This assay shows potential to select anti-mitochondrial drugs as
      a first screen. This should be followed up by more specific in vitro and in vivo
      tests to pinpoint the type of anti-mitochondrial activity exerted by these drugs,
      if any. This is because the possibility exists that compounds regarded as anti
      mitochondrial may not inhibit mitochondrial function but other fruiting structure
      developmental stages and therefore yield false positives. To enhance our
      knowledge on how these drugs act at the structural level, the authors recommend
      Nano Scanning Auger Microscopy as the tool of choice.

PMID- 22646156
TI  - Lipid production in batch and fed-batch cultures of Rhodosporidium toruloides
      from 5 and 6 carbon carbohydrates.
AB  - BACKGROUND: Microbial lipids are a potential source of bio- or renewable diesel
      and the red yeast Rhodosporidium toruloides is interesting not only because it
      can accumulate over 50% of its dry biomass as lipid, but also because it utilises
      both five and six carbon carbohydrates, which are present in plant biomass
      hydrolysates. METHODS: R. toruloides was grown in batch and fed-batch cultures in
      0.5 L bioreactors at pH 4 in chemically defined, nitrogen restricted (C/N 40 to
      100) media containing glucose, xylose, arabinose, or all three carbohydrates as
      carbon source. Lipid was extracted from the biomass using chloroform-methanol,
      measured gravimetrically and analysed by GC. RESULTS: Lipid production was most
      efficient with glucose (up to 25 g lipid L(-1), 48 to 75% lipid in the biomass,
      at up to 0.21 g lipid L(-1) h(-1)) as the sole carbon source, but high lipid
      concentrations were also produced from xylose (36 to 45% lipid in biomass). Lipid
      production was low (15-19% lipid in biomass) with arabinose as sole carbon source
      and was lower than expected (30% lipid in biomass) when glucose, xylose and
      arabinose were provided simultaneously. The presence of arabinose and/or xylose
      in the medium increased the proportion of palmitic and linoleic acid and reduced
      the proportion of oleic acid in the fatty acids, compared to glucose-grown cells.
      High cell densities were obtained in both batch (37 g L(-1), with 49% lipid in
      the biomass) and fed-batch (35 to 47 g L(-1), with 50 to 75% lipid in the
      biomass) cultures. The highest proportion of lipid in the biomass was observed in
      cultures given nitrogen during the batch phase but none with the feed. However,
      carbohydrate consumption was incomplete when the feed did not contain nitrogen
      and the highest total lipid and best substrate consumption were observed in
      cultures which received a constant low nitrogen supply. CONCLUSIONS: Lipid
      production in R. toruloides was lower from arabinose and mixed carbohydrates than
      from glucose or xylose. Although high biomass and lipid production were achieved
      in both batch and fed-batch cultures with glucose as carbon source, for lipid
      production from mixtures of carbohydrates fed-batch cultivation was preferable.
      Constant feeding was better than intermittent feeding. The feeding strategy did
      not affect the relative proportion of different fatty acids in the lipid, but the
      presence of C5 sugars did.

PMID- 22646157
TI  - Clopidogrel plus indobufen in acute coronary syndrome patients with
      hypersensitivity to aspirin undergoing percutaneous coronary intervention.
AB  - The prescription of aspirin (acetylsalicylic acid (ASA)) to patients with a
      history of hypersensitivity to this drug could prove harmful. The aim of the
      study was to assess the antiplatelet activity and safety of a combined
      antiplatelet treatment with indobufen and clopidogrel in acute coronary syndrome
      (ACS) patients with hypersensitivity to aspirin, undergoing coronary stenting.
      Forty-two consecutive ACS patients treated with stent implantation were randomly
      assigned to receive clopidogrel 75 mg daily (loading dose 300 mg) plus indobufen
      100 mg twice a day (group A), or clopidogrel 75 mg daily, after 300 mg of loading
      dose (group B). Platelet activity and safety were monitored in both groups at 1,
      3, 6, 12, and 18 months with laboratory and clinical evaluation. A lower value of
      max % platelet aggregation to arachidonic acid and collagen was found in group A
      compared to group B (31.79 +/- 27.33 vs. 73.67 +/- 19.92; p < 0.0001 and 28.53 +/
      21.32 vs. 73.58 +/- 17.71; p < 0.0001, respectively). There was no difference in
      max % of platelet inhibition to adenosine diphosphate between the two groups
      (14.23 +/- 18.92 vs. 10.30 +/- 18.97; p = 0.23). In the population that was under
      indobufen treatment, the serum thromboxane B2 (TXB2) production at 1 week and 1
      month was very low (2.6 +/- 1.6 ng/ml and 3.0 +/- 2.7 ng/ml, respectively; p =
      0.82). The combined treatment was well tolerated in group A patients. This study
      suggests that the combined antiplatelet treatment with clopidogrel and indobufen
      could be a good option in ACS patients with hypersensitivity to aspirin
      undergoing coronary stenting.

PMID- 22646159
TI  - Overestimation of the probability of death on peritoneal dialysis by the Kaplan
      Meier method: advantages of a competing risks approach.
AB  - BACKGROUND: In survival analysis, patients on peritoneal dialysis are confronted
      with three different outcomes: transfer to hemodialysis, renal transplantation,
      or death. The Kaplan-Meier method takes into account one event only, so whether
      it adequately considers these different risks is questionable. The more recent
      competing risks method has been shown to be more appropriate in analyzing such
      situations. METHODS: We compared the estimations obtained by the Kaplan-Meier
      method and the competing risks method (namely the Kalbfleisch and Prentice
      approach), in 383 consecutive incident peritoneal dialysis patients. By means of
      simulations, we then compared the Kaplan-Meier estimations obtained in two
      virtual centers where patients had exactly the same probability of death. The
      only difference between these two virtual centers was whether renal
      transplantation was available or not. RESULTS: At five years, 107 (27.9%)
      patients had died, 109 (28.4%) had been transferred to hemodialysis, 91 (23.8%)
      had been transplanted, and 37 (9.7%) were still alive on peritoneal dialysis;
      before five years, 39 (10.2%) patients were censored alive on peritoneal
      dialysis. The five-year probabilities estimated by the Kaplan-Meier and the
      competing risks methods were respectively: death: 50% versus 30%; transfer to
      hemodialysis: 59% versus 32%; renal transplantation: 39% versus 26%; event-free
      survival: 12% versus 12%. The sum of the Kaplan-Meier estimations exceeded 100%,
      implying that patients could experience more than one event, death and
      transplantation for example, which is impossible. In the simulations, the
      probability of death estimated by the Kaplan-Meier method increased as the
      probability of renal transplantation increased, although the probability of death
      actually remained constant. CONCLUSION: The competing risks method appears more
      appropriate than the Kaplan-Meier method for estimating the probability of events
      in peritoneal dialysis in the context of univariable survival analysis.

PMID- 22646158
TI  - Functional and genetic interactions of TOR in the budding yeast Saccharomyces
      cerevisiae with myosin type II-deficiency (myo1Delta).
AB  - BACKGROUND: Yeast has numerous mechanisms to survive stress. Deletion of myosin
      type II (myo1Delta) in Saccharomyces cerevisiae results in a cell that has
      defective cytokinesis. To survive this genetically induced stress, this budding
      yeast up regulates the PKC1 cell wall integrity pathway (CWIP). More recently,
      our work indicated that TOR, another stress signaling pathway, was down regulated
      in myo1Delta strains. Since negative signaling by TOR is known to regulate PKC1,
      our objectives in this study were to understand the cross-talk between the TOR
      and PKC1 signaling pathways and to determine if they share upstream regulators
      for mounting the stress response in myo1Delta strains. RESULTS: Here we proved
      that TORC1 signaling was down regulated in the myo1Delta strain. While a
      tor1Delta mutant strain had increased viability relative to myo1Delta, a combined
      myo1Deltator1Delta mutant strain showed significantly reduced cell viability.
      Synthetic rescue of the tor2-21(ts) lethal phenotype was observed in the
      myo1Delta strain in contrast to the chs2Delta strain, a chitin synthase II null
      mutant that also activates the PKC1 CWIP and exhibits cytokinesis defects very
      similar to myo1Delta, where the rescue effect was not observed. We observed two
      pools of Slt2p, the final Mitogen Activated Protein Kinase (MAPK) of the PKC1
      CWIP; one pool that is up regulated by heat shock and one that is up regulated by
      the myo1Delta stress. The cell wall stress sensor WSC1 that activates PKC1 CWIP
      under other stress conditions was shown to act as a negative regulator of TORC1
      in the myo1Delta mutant. Finally, the repression of TORC1 was inversely
      correlated with the activation of PKC1 in the myo1Delta strain. CONCLUSIONS:
      Regulated expression of TOR1 was important in the activation of the PKC1 CWIP in
      a myo1Delta strain and hence its survival. We found evidence that the PKC1 and
      TORC1 pathways share a common upstream regulator associated with the cell wall
      stress sensor WSC1. Surprisingly, essential TORC2 functions were not required in
      the myo1Delta strain. By understanding how yeast mounts a concerted stress
      response, one can further design pharmacological cocktails to undermine their
      ability to adapt and to survive.

PMID- 22646161
TI  - The role of GlpR repressor in Pseudomonas putida KT2440 growth and PHA production
      from glycerol.
AB  - Pseudomonas putida KT2440 has evolved a tightly regulated system for metabolizing
      glycerol implying a prolonged growth lag-phase. We have learnt that this fact can
      be avoided by the addition of small amounts of some growth precursors. The
      addition of 1 mM octanoic acid as co-feeder completely eliminated the lag-phase,
      resulting in an improvement, in terms of invested time, of both growth and
      polyhydroxyalkanoates (PHA) accumulation. To investigate this phenomenon, we have
      followed co-metabolic approaches combined with mutations of the specific and
      global regulatory networks that connect glycerol catabolism and PHA synthesis. By
      using mutant strains in metabolic genes from the PHA and tricarboxylic acid (TCA)
      cycles, we have demonstrated that the co-feeding effect is independent of PHA
      accumulation, but driven on active glyoxylate shunt and Entner-Doudoroff (ED)
      routes. These findings suggested that the effect of octanoate on glycerol
      metabolism could rely, either on a global activation of the cell energy state, or
      on the generation of specific metabolites or cofactors needed for the activation
      of glycerol metabolism. Our results addressed GlpR as the key factor controlling
      the efficient utilization of glycerol as growth precursor in P. putida KT2440.
      Accordingly, a glpR knockout mutant of P. putida KT2440 showed an elimination of
      the lag-phase when cultured on glycerol in the absence of co-feeder. Besides, the
      production of PHA in this strain was increased near twofold, resulting in a
      higher final yield in terms of PHA accumulation. The repressor activity of the
      GlpR protein over the glp genes in the absence of glycerol was finally
      demonstrated by qRT-PCR. This work contributed to unravel the physiological
      causes of the long lag-phase produced by glycerol in the model strain P. putida
      KT2440 that hinders its use as carbon source in biotechnological applications for
      generating valuable products.

PMID- 22646160
TI  - Gene expression profiling of Mycobacterium avium subsp. paratuberculosis in
      simulated multi-stress conditions and within THP-1 cells reveals a new kind of
      interactive intramacrophage behaviour.
AB  - BACKGROUND: Recent studies have identified in Mycobacterium avium subsp.
      paratuberculosis (MAP), already known as a pathogen in ruminants, a potential
      zoonotic agent of some autoimmune diseases in humans. Therefore, considering the
      possible risk for public health, it is necessary a thorough understanding of
      MAP's gene expression during infection of human host as well as the
      identification of its immunogenic and/or virulence factors for the development of
      appropriate diagnostic and therapeutic tools. RESULTS: In order to characterize
      MAP's transcriptome during macrophage infection, we analyzed for the first time
      the whole gene expression of a human derived strain of MAP in simulated
      intraphagosomal conditions and after intracellular infection of the human
      macrophage cell line THP-1 by using the DNA-microarray technology. Results showed
      that MAP shifts its transcriptome to an adaptive metabolism for an anoxic
      environment and nutrient starvation. It up-regulates several response factors to
      oxidative stress or intracellular conditions and allows, in terms of
      transcription, a passive surface peptidoglycan spoliation within the macrophage
      along with an intensification of the anabolic activity for lipidic membrane
      structures. CONCLUSIONS: These results indicate a possible interactive system
      between MAP and its host cell based on the internal mimicry unlike other
      intracellular pathogens, bringing new hypothesis in the virulence and
      pathogenicity of MAP and its importance in human health.

PMID- 22646162
TI  - Facile preparation route for nanostructured composites: surface-initiated ring
      opening polymerization of epsilon-caprolactone from high-surface-area nanopaper.
AB  - In this work, highly porous nanopaper, i.e., sheets of papers made from non
      aggregated nanofibrillated cellulose (NFC), have been surface-grafted with
      poly(epsilon-caprolactone) (PCL) by surface-initiated ring-opening polymerization
      (SI-ROP). The nanopaper has exceptionally high surface area (~300 m(2)/g). The
      "grafting from" of the nanopapers was compared to "grafting from" of cellulose in
      the form of filter paper, and in both cases either titanium n-butoxide (Ti(On
      Bu)4) or tin octoate (Sn(Oct)2) was utilized as a catalyst. It was found that a
      high surface area leads to significantly higher amount of grafted PCL in the
      substrates when Sn(Oct)2 was utilized as a catalyst. Up to 79 wt % PCL was
      successfully grafted onto the nanopapers as compared to filter paper where only 2
      3 wt % PCL was grafted. However, utilizing Ti(On-Bu)4 this effect was not seen
      and the grafted amount was essentially similar, irrespectively of surface area.
      The mechanical properties of the grafted nanopaper proved to be superior to those
      of pure PCL films, especially at elevated temperatures. The present bottom-up
      preparation route of NFC-based composites allows high NFC content and provides
      excellent nanostructural control. This is an important advantage compared with
      some existing preparation routes where dispersion of the filler in the matrix is
      challenging. 

PMID- 22646163
TI  - Kinetics of the interaction between anti-FVIII antibodies and FVIII from
      therapeutic concentrates, with and without von Willebrand factor, assessed by
      surface plasmon resonance.
AB  - The presence of VWF in plasma-derived FVIII (pdFVIII/VWF) products has been
      pointed out as a key difference with recombinant FVIII (rFVIII) products with
      regard to immunogenicity. A Surface Plasmon Resonance (SPR) study was designed to
      characterize in detail the interaction between anti-FVIII (IgGs) from a severe
      haemophilia A patient, and FVIII from concentrates of different sources. Full
      length rFVIII (preincubated or not with purified VWF), B domain-deleted (BDD)
      rFVIII and pdFVIII/VWF were analysed. To ensure reproducible conditions for
      accurate determination of kinetic constants, a capture-based assay format was
      developed using protein G surfaces for specific and reversible coupling of
      endogenous anti-FVIII antibodies. Concentration ranges (nm) of FVIII products
      tested were 9-0.03 (rFVIII) and 6-0.024 (pdFVIII/VWF). The association with
      antibodies was monitored for 3-5 min, whereas dissociation of the complex was
      followed for 5-20-240 min. A strong interaction of rFVIII and BDD-rFVIII with
      patient's IgG was detected with the K (D) values in the low picomolar range (5.9
      +/- 3.0 and 12.7 +/- 6.9 pm, respectively) and very slow dissociation rates,
      while pdFVIII/VWF showed only marginal binding signals. The VWF complexed rFVIII
      displayed reduced binding signals compared with uncomplexed rFVIII, but the K (D)
      was still in the picomolar range (4.1 +/- 1.9 pm) indicating insufficient complex
      formation. rFVIII, alone or bound to exogenously added VWF, showed high affinity
      for anti-FVIII IgGs from a severe haemophilia A patient whereas pdFVIII/VWF did
      not. These results are in agreement with those studies that point towards rFVIII
      concentrates to be more immunogenic than pdFVIII concentrates.

PMID- 22646164
TI  - Alternative donor HSCT in refractory acquired aplastic anemia: the time has come.

PMID- 22646165
TI  - Expression of NOS isoforms in internal spermatic veins of infertile men with
      varicocele.
AB  - Although varicocele is a relatively common entity encountered in the evaluation
      of infertile men, the exact pathophysiology still remains unclear. Recently, as
      previously widely investigated in various parts of human circulatory system,
      nitric oxide synthase (NOS) and its product, nitric oxide (NO) have been thought
      to play a role in the development of varicocele and thus male infertility. In
      this study, we determined the concentration of NO metabolite and the expression
      of NOS isoforms in the internal spermatic (ISV) and superficial branch of
      inferior epigastric veins of infertile men with varicocele. The study included 60
      infertile men with clinically unilateral or bilateral varicocele. Expression of
      inducible and endothelial NOS (iNOS and eNOS) isoforms were investigated in
      tissue arrays of internal spermatic and superficial branch of inferior epigastric
      veins with immunohistochemistry. NO metabolite (nitrite) levels were measured
      using the calorimetric method. A significantly higher expression of eNOS was
      observed in the varicose veins (mean score: 2.25 and 1.55, respectively; p =
      0.0001). However, statistically, there was no significant difference for
      expression of iNOS between varicose and control veins (p = 0.094). The nitrite
      concentration and NOS expression were not found to be correlated with clinical
      variables (varicocele grade, maximum varicose vein diameter, and sperm
      concentration, motility, and morphology) (p > 0.05). As a result, the
      significantly higher expression of eNOS in ISV may be responsible for the
      development of varicocele, although this finding is not accompanied by an
      increase in NO concentration. Still, the pattern of the relationship between
      varicocele and increased eNOS expression warrants further investigation.

PMID- 22646168
TI  - What do these nobel laureates have in common?

PMID- 22646169
TI  - The obligation to publish.

PMID- 22646167
TI  - Randomised clinical trial: simvastatin as adjuvant therapy improves significantly
      the Helicobacter pylori eradication rate--a placebo-controlled study.
AB  - BACKGROUND: The eradication rate of Helicobacter pylori with standard treatments
      are decreasing worldwide. AIM: To determine whether adding simvastatin as
      adjuvant to triple regimen in patients with H. pylori infection will improve the
      eradication rate. METHODS: We conducted a double-blind, placebo-controlled,
      randomised clinical trial comparing a 7-day, triple eradication regimen
      consisting of two antibiotics (clarithromycin 500 mg and amoxicillin 1 g, all
      twice per day) plus a proton pump inhibitor (omeprazole 20 mg twice daily)
      supplemented with simvastatin 20 mg (CAO + S) or a comparable placebo (CAO + P).
      Both the simvastatin and the placebo were taken orally twice daily for 1 week in
      113 patients with H. pylori infection. The presence of H. pylori was determined
      by positive rapid urease test and histology. Eradication was confirmed by 13C
      urea breath test at least 1 month after treatment. Adverse effects were assessed
      by questionnaire. RESULTS: A total of 113 patients underwent randomisation.
      Intention-to-treat analysis (ITT; n = 113) eradication rates were: CAO + S (86%;
      95% CI: 78-92%), CAO + P (69%; 95% CI: 64-74%). Per protocol analysis (PP; n =
      108) eradication rates were: CAO + S (91%; 95% CI: 84-94%), CAO + P (72%; 95% CI:
      65-78%). Eradication rates were higher with CAO + S than CAO + P in PP and ITT (P
      = 0.03, P = 0.04 respectively). No differences were demonstrated between the two
      groups concerning compliance or adverse effects. CONCLUSION: In this randomised
      clinical trial simvastatin as adjuvant to standard therapy improves significantly
      the H. pylori eradication rate.

PMID- 22646166
TI  - The RNA-binding protein CUG-BP1 increases survivin expression in oesophageal
      cancer cells through enhanced mRNA stability.
AB  - Survivin, a member of the IAP (inhibitor of apoptosis protein) family, plays
      important roles in maintaining cellular homoeostasis and regulating cell-cycle
      progression. This IAP is overexpressed in oesophageal cancer cells, leading to
      uncontrolled cell growth and resistance to apoptosis. CUG-BP1 (CUG-binding
      protein 1) is an RNA-binding protein that regulates the stability and
      translational efficiency of target mRNAs. In the present paper, we report that
      CUG-BP1 is overexpressed in oesophageal cancer cell lines and human oesophageal
      cancer specimens. CUG-BP1 associates with the 3'-untranslated region of survivin
      mRNA, thereby stabilizing the transcript and elevating its expression in
      oesophageal cancer cells. Our results show that overexpression of CUG-BP1 in
      oesophageal epithelial cells results in increased survivin mRNA stability and
      consequently survivin protein expression. Conversely, silencing CUG-BP1 in
      oesophageal cancer cells destabilizes survivin mRNA, lowering the level of
      survivin protein. In addition, we have found that altering CUG-BP1 expression
      modulates susceptibility to chemotherapy-induced apoptosis. Overexpression of CUG
      BP1 in oesophageal epithelial cells increases resistance to apoptosis, whereas
      silencing CUG-BP1 makes oesophageal cancer cells more susceptible to chemotherapy
      induced apoptosis. Co-transfection experiments with small interfering RNA
      directed against survivin suggest that the anti-apoptotic role for CUG-BP1 is not
      entirely dependent on its effect on survivin expression.

PMID- 22646170
TI  - States.

PMID- 22646171
TI  - Washington.

PMID- 22646173
TI  - Science.

PMID- 22646172
TI  - International.

PMID- 22646175
TI  - Industry.

PMID- 22646174
TI  - Technology.

PMID- 22646176
TI  - Focuses on the ways polymers.

PMID- 22646177
TI  - Reviews recent progress in plutonium.

PMID- 22646178
TI  - Exposure to chemical waste sites.

PMID- 22646180
TI  - Chlorinated hydrocarbon wastes.

PMID- 22646179
TI  - Singer named associate editor.

PMID- 22646182
TI  - Revamping RCRA.

PMID- 22646181
TI  - We're not the new kid on the block anymore.

PMID- 22646183
TI  - Acid deposition and forest decline.

PMID- 22646185
TI  - Regulatory information systems.

PMID- 22646184
TI  - Space is Money.

PMID- 22646186
TI  - Atmospheric ozone-olefin reactions.

PMID- 22646187
TI  - Products.

PMID- 22646188
TI  - Electric power research institute.

PMID- 22646189
TI  - Literature.

PMID- 22646193
TI  - professional consulting services directory.

PMID- 22646192
TI  - Classified section.

PMID- 22646194
TI  - International.

PMID- 22646197
TI  - Research priorities for preventing depression.

PMID- 22646196
TI  - Cardiac changes in horses with atypical myopathy.
AB  - BACKGROUND: Atypical myopathy (AM) is an acute, fatal rhabdomyolysis in grazing
      horses that mainly affects skeletal muscles. Postmortem examinations have shown
      that myocardial damage also occurs. Limited information is available on the
      effect of AM on cardiac function in affected and surviving horses. OBJECTIVES: To
      describe electrocardiographic and echocardiographic changes associated with AM in
      the acute stage of the disease and after follow-up. ANIMALS: Horses (n = 12)
      diagnosed with AM in which cardiac ultrasound examination and ECG recording were
      available. METHODS: All horses underwent clinical examinations, serum
      biochemistry, electrocardiography, and echocardiography. Four surviving horses
      underwent the same examinations after 2-10 weeks. RESULTS: All but 1 horse had
      increased cardiac troponin I concentrations and 10 horses had ventricular
      premature depolarizations (VPDs). All horses had prolonged corrected QT (QT(cf) )
      intervals on the day of admission and abnormal myocardial wall motion on
      echocardiography. One of the surviving horses still had VPDs and prolonged QT(cf)
      at follow-up after 10 weeks. CONCLUSIONS AND CLINICAL IMPORTANCE: The AM results
      in characteristic electrocardiographic and echocardiographic changes and may be
      associated with increased cardiac troponin I concentrations and VPDs. In
      survivors, abnormal cardiac function still may be found at follow-up after 10
      weeks. Additional research in a larger group of horses is necessary to identify
      the long-term effects of AM on cardiac function.

PMID- 22646198
TI  - Gay children and suicidality: the importance of professional nurturance.
AB  - Suicidality among young people is a global concern, with international studies
      demonstrating an increased prevalence among young gay men. Being gay is not
      inevitably linked to mental illness, but growing up gay in a heterosexist society
      can compromise mental well being. This qualitative study, using free association
      narrative interviewing, offers an in-depth understanding of gay men's experience.
      One shared experience that emerged was "knowing and not knowing," the story of
      gay children growing up in a heterosexist society. This story provides valuable
      insights for mental health nurses becoming more attuned to the importance of
      providing professional nurturing of gay children.

PMID- 22646199
TI  - Helpful and challenging support encounters in the aftermath of HPV infection and
      diagnosis.
AB  - Infection and diagnosis with HPV create significant support needs, yet the
      support experiences and evaluations of women with HPV remain unexplored. This
      study identified supportive communication behavior perceived as helpful or
      problematic by women with HPV. Interviews with 25 participants revealed that
      women find it helpful when supportive others: (a) provide reassurance,
      information, and validation; (b) attend appointments; (c) facilitate
      reappraisals; and, (d) listen. Findings also highlighted support challenges, such
      as disclosure difficulties and problems locating and accessing support groups.
      The discussion focuses on explanations for and implications of variations in
      enacted support quality for women with HPV and others managing chronic illnesses.

PMID- 22646200
TI  - Preliminary validity and reliability of the Sickle Cell Disease Health-Related
      Stigma Scale.
AB  - There have been no published studies that measure health-related stigma in
      individuals with sickle cell disease (SCD). This study provides preliminary
      validity and reliability of the Sickle Cell Disease Health-Related Stigma Scale
      (SCD-HRSS). Using a sample of 77 young adults with SCD, ages 18-35 years, the
      results support the reliability of the SCD-HRSS with an overall Cronbach's alpha
      reliability of 0.84 and construct validity with a positive correlation between
      SCD-HRSS and a measure of depressive symptoms. Participants reported the highest
      levels of perceived stigma from the general public, then doctors, and lastly
      family. Limitations and directions for future research are discussed.

PMID- 22646201
TI  - Marital adjustment and depressive symptoms in Korean Americans.
AB  - The purpose of this study was to explore the relationship between the quality of
      marital adjustment and depressive symptoms in Korean American couples. Fifty
      three wives and 19 husbands reported on the Dyadic Adjustment Scale and the
      Center for Epidemiologic Studies for Depression Scale. Results from linear
      regression indicated a negative relationship between marital adjustment and
      depressive symptoms at a significant level for wives and near significant for
      husbands. The model explained 15% of the variance in wives' depressive symptoms.
      The negative impact of marital adjustment on depressive symptoms indicates that
      Korean American couples' marital adjustments need to be addressed.

PMID- 22646202
TI  - Unveiling new dimensions: a hermeneutic exploration of perinatal mood disorder
      and infant feeding.
AB  - In this hermeneutic study, six women from the local Perinatal Mental Health
      Program were interviewed about their experiences with infant feeding. None of the
      women in the study were breastfeeding their infants. The research question
      centered on their experience of formula feeding with a view to gaining better
      insight about the issues that women face when feeding practices do not conform to
      best-practice (i.e., breastfeeding) promotional standards. We also considered the
      needs of nurses working in the mental health setting, who may face conflicting
      recommendations concerning the treatment of a mental health crisis in the
      presence of current infant feeding best-practice guidelines. Our findings support
      concerns that current guidelines overlook the special needs of women who live
      with perinatal mood disorder. We speculate that breastfeeding challenges may
      present a risk for postpartum depression in women who are biologically
      vulnerable. The need for ongoing assessment for emerging depression among women
      who are experiencing breastfeeding challenges is identified. The importance of
      deepened understanding among mental health nurses is highlighted.

PMID- 22646203
TI  - Basic attitudes toward life expressed by persons with long-term mental illness
      living in a Swedish community.
AB  - Previous research has shown that persons with long-term mental illness who
      require prolonged treatment and social support wish to, yet find it difficult to,
      find meaning or quality in life. A descriptive qualitative design using self
      photography and in-depth interviews was used for data collection. The aim of this
      study was to explore basic attitudes to life as expressed by nine persons with
      long-term mental illness living in the community. The findings provide insight
      into the values of relationships, work, and the home for persons with long-term
      mental illness and indicate that they are cognizant of social norms yet have
      difficulty integrating these in their daily lives. The study also illuminates the
      informants' difficulties in creating satisfying and supporting relationships with
      others.

PMID- 22646204
TI  - Beginning the recovery journey in acute psychiatric care: using concepts from
      Orem's Self-Care Deficit Nursing Theory.
AB  - A national agenda has been established for mental health systems to move toward a
      recovery model of care. Recovery principles are embedded in the foundations of
      nursing science and practice. Orem's Self-Care Deficit Nursing Theory (SCDNT) is
      in alignment with the ideals of recovery and can provide a structure for changing
      cultures on inpatient psychiatric units. SCDNT can guide research activities that
      link a patient's self-care abilities to improved recovery model outcomes. This
      paradigm shift is an opportunity for psychiatric nursing to return to its roots
      and deliver care that is patient-centered and conducive to recovering from mental
      illness.

PMID- 22646206
TI  - Death bed promise: burden or blessing?

PMID- 22646208
TI  - Does thinking and doing the same thing amount to involved participation?
      Empirical explorations for finding a measure of intensity for a third ICF-CY
      qualifier.
AB  - BACKGROUND: Participation as involvement in a situation includes two dimensions;
      doing the activity and the experience of involvement. OBJECTIVES: The ICF-CY only
      measures doing using the capacity and performance qualifiers, a dimension
      measuring the experience is needed; a third qualifier. HYPOTHESIS: The
      experienced involvement of pupils in school activities is higher when thinking
      and doing coincided. METHODS: By comparing self-reported experiences of
      involvement of children, data about what children were thinking and doing during
      activities were gathered from 21 children with and 19 without disabilities in
      inclusive classrooms. RESULTS: A relationship exists between an index of the
      subjective experience of involvement and whether children were thinking and doing
      the same things. CONCLUSION: This index can be constructed using measures of
      concentration, control, involvement, and motivation. Choice is influential, as
      knowledge about why an activity is undertaken affects involvement. Additionally,
      increased subjective experience of involvement gives better psychological health
      and well-being.

PMID- 22646209
TI  - Two cases of cervical artery dissection with cerebral ischemic recurrences due to
      heparin-induced thrombocytopenia.

PMID- 22646210
TI  - An iron-sulfur cluster loop motif in the Archaeoglobus fulgidus uracil-DNA
      glycosylase mediates efficient uracil recognition and removal.
AB  - The family 4 uracil-DNA glycosylase from the hyperthermophilic organism
      Archaeoglobus fulgidus (AFUDG) is responsible for the removal of uracil in DNA as
      the first step in the base excision repair (BER) pathway. AFUDG contains a large
      solvent-exposed peptide region containing an alpha helix and loop anchored on
      each end via ligation of two cysteine thiolates to a [4Fe-4S](2+) cluster. We
      propose that this region plays a similar role in DNA damage recognition as a
      smaller iron-sulfur cluster loop (FCL) motif in the structurally unrelated BER
      glycosylases MutY and Endonuclease III and therefore refer to this region as the
      "pseudo-FCL" in AFUDG. In order to evaluate the importance of this region, three
      positively charged residues (Arg 86, Arg 91, Lys 100) and the anchoring Cys
      residues (Cys 85, Cys 101) within this motif were replaced with alanine, and the
      effects of these replacements on uracil excision in single- and double-stranded
      DNA were evaluated. These results show that this region participates and allows
      for efficient recognition and excision of uracil within DNA. Notably, R86A AFUDG
      exhibited reduced activity for uracil removal only within double-stranded DNA,
      suggesting an importance in duplex disruption and extrusion of the base as part
      of the excision process. In addition, mutation of the [4Fe-4S](2+) cluster
      cysteine ligands at the ends of the pseudo-FCL to alanine reduced the uracil
      excision efficiency, suggesting the importance of anchoring the loop via
      coordination to the cluster. In contrast, K100A AFUDG exhibited enhanced uracil
      excision activity, providing evidence for the importance of the loop conformation
      and flexibility. Taken together, the results herein provide evidence that the
      pseudo-FCL motif is involved in DNA binding and catalysis, particularly in duplex
      DNA contexts. This work underscores the requirement of an ensemble of
      interactions, both distant and in proximity to the damaged site, for accurate and
      efficient uracil excision.

PMID- 22646211
TI  - Strategies of multi-objective optimization in drug discovery and development.
AB  - INTRODUCTION: Drug discovery and development is a typical multi-objective problem
      and its successes or failures depend on the simultaneous control of numerous,
      often conflicting, molecular and pharmacological properties. Multi-objective
      optimization strategies represent a new approach to capture the occurrence of
      varying optimal solutions based on trade-offs among the objectives taken into
      account. In view of this, multi-objective optimization aims to discover a set of
      satisfactory compromises that may in turn be used to find the global optimal
      solution by optimizing numerous dependent properties simultaneously. AREAS
      COVERED: The authors review the potential of multi-objective strategies in a
      number of fields including: drug library design; substructure mining; the
      derivation of quantitative structure-activity relationship models; ranking of
      docking poses. The authors also discuss the potential of multi-objective
      strategies in controlling competing properties for absorption, distribution,
      metabolism and elimination/toxicity optimization. EXPERT OPINION: It is very
      clear to those who work in drug discovery and development that the success of
      rational drug design is largely dependent on the control of a number of, often
      conflicting, objectives. Therefore, multi-objective optimization methods, which
      have recently been introduced to the field of molecular discovery, represent the
      ultimate frontier in chemoinformatics. The widespread use of these multi
      objective techniques has provided new opportunities in medicinal chemistry as
      seen through its use in a number of applications for chemoinformatics both within
      academia and the pharmaceutical industry.

PMID- 22646212
TI  - Web-based services for drug design and discovery.
AB  - INTRODUCTION: Reviews of the development of drug discovery through the 20(th)
      century recognised the importance of chemistry and increasingly bioinformatics,
      but had relatively little to say about the importance of computing and networked
      computing in particular. However, the design and discovery of new drugs is
      arguably the most significant single application of bioinformatics and
      cheminformatics to have benefitted from the increases in the range and power of
      the computational techniques since the emergence of the World Wide Web, commonly
      now referred to as simply 'the Web'. Web services have enabled researchers to
      access shared resources and to deploy standardized calculations in their search
      for new drugs. AREAS COVERED: This article first considers the fundamental
      principles of Web services and workflows, and then explores the facilities and
      resources that have evolved to meet the specific needs of chem- and bio
      informatics. This strategy leads to a more detailed examination of the basic
      components that characterise molecules and the essential predictive techniques,
      followed by a discussion of the emerging networked services that transcend the
      basic provisions, and the growing trend towards embracing modern techniques, in
      particular the Semantic Web. EXPERT OPINION: In the opinion of the authors, the
      issues that require community action are: increasing the amount of chemical data
      available for open access; validating the data as provided; and developing more
      efficient links between the worlds of cheminformatics and bioinformatics. The
      goal is to create ever better drug design services.

PMID- 22646213
TI  - Lessons learned from the preclinical drug discovery of asoprisnil and ulipristal
      for non-surgical treatment of uterine leiomyomas.
AB  - INTRODUCTION: Uterine leiomyoma is the most common benign tumor in women during
      the reproductive years. Menorrhagia is the common symptom and accounts for the
      most frequent indication for hysterectomy. Thus, development of a novel drug for
      non-surgical treatment of uterine leiomyoma is needed for the betterment of
      women's health. AREA COVERED: This review introduces a translational research
      initiated by use of the levonorgestrel-releasing intrauterine system (LNG-IUS)
      for contraceptive purposes. During follow-up, a patient informed that heavy
      menstrual bleeding caused by uterine myoma was strikingly reduced after the
      insertion of device. The patient's unexpected comment led the authors to perform
      clinical trials of LNG-IUS for the management of menorrhagia in women with
      uterine myomas and striking reduction in menorrhagia was obtained by the use of
      LNG-IUS. MRI examination, however, revealed that the volume of myomas decreased
      in some, but increased in the other instances. This unexpected finding with MRI
      directed the authors to characterize the effects of progesterone (P4) and
      progesterone receptor modulators (PRMs) on uterineleiomyoma cell growth in vitro.
      EXPERT OPINION: In consistence with the in vitro data obtained, randomized
      controlled clinical trials of PRMs in patients with uterine leiomyomas at several
      institutions have demonstrated that oral administration of PRMs (asoprisnil and
      ulipristal) for 3 months reduced leiomyoma volume, resulting in a significant
      improvement of the associated symptoms. However, a novel pattern of PRM
      associated endometrial changes was recognized in the endometrial pathology,
      demonstrating unusual epithelial types not seen in the normal menstrual cycle of
      a premenstrual woman. Thus, follow-up studies to determine whether the novel
      endometrial changes remain, disappear or progress to something else are needed
      for the possible long-term use of PRMs for the treatment of uterine leiomyoma.

PMID- 22646214
TI  - Application of drug efficiency index in drug discovery: a strategy towards low
      therapeutic dose.
AB  - INTRODUCTION: The ultimate objective of optimizing adsorption, distribution,
      metabolism and excretion (ADME) parameters in drug discovery is to maximize the
      unbound concentration at the site of action for a given dose level. This has the
      added benefit of minimizing the efficacious dose, reducing the potential for
      attrition related to drug burden and direct organ toxicity. The concept of drug
      efficiency was formulated as a tool to obtain a balanced profile between target
      affinity and ADME properties during lead optimization. AREAS COVERED: The authors
      discuss how it is possible to maximize the in vivo pharmacological potential
      addressing whether drug efficiency adds value to the decision-making process and
      whether it is possible to introduce a single optimization parameter, the drug
      efficiency index (DEI), linking target affinity and ADME properties, as a marker
      of in vivo efficacy. EXPERT OPINION: In the absence of a clear hypothesis-driven
      approach at the beginning of the program (i.e., pharmacokinetic-pharmacodynamic
      link), the objective to select molecules with a low therapeutic dose is still a
      major hurdle in drug discovery. The authors believe that a greater strategic
      focus on mechanistically relevant measures of the determinants of receptor
      occupancy would help the optimization and selection process. In this respect, the
      introduction of the DEI, which can be seen as a correction of target affinity by
      the in vivo pharmacokinetic potential, may help drug discovery to select and
      promote those molecules with the highest probability to interact with the
      biological target and with the best balance between target affinity and ADME
      properties.

PMID- 22646215
TI  - Recent advances in protein-protein interaction prediction: experimental and
      computational methods.
AB  - INTRODUCTION: Proteins within the cell act as part of complex networks, which
      allow pathways and processes to function. Therefore, understanding how proteins
      interact is a significant area of current research. AREAS COVERED: This review
      aims to present an overview of key experimental techniques (yeast two-hybrid,
      tandem affinity purification and protein microarrays) used to discover protein
      protein interactions (PPIs), as well as to briefly discuss certain computational
      methods for predicting protein interactions based on gene localization,
      phylogenetic information, 3D structural modeling or primary protein sequence
      data. Due to the large-scale applicability of primary sequence-based methods, the
      authors have chosen to focus on this strategy for our review. There is an
      emphasis on a recent algorithm called Protein Interaction Prediction Engine
      (PIPE) that can predict global PPIs. The readers will discover recent advances
      both in the practical determination of protein interaction and the strategies
      that are available to attempt to anticipate interactions without the time and
      costs of experimental work. EXPERT OPINION: Global PPI maps can help understand
      the biology of complex diseases and facilitate the identification of novel drug
      target sites. This study describes different techniques used for PPI prediction
      that we believe will significantly impact the development of the field in a new
      future. We expect to see a growing number of similar techniques capable of large
      scale PPI predictions.

PMID- 22646216
TI  - Stabilized helical peptides: overview of the technologies and therapeutic
      promises.
AB  - INTRODUCTION: Helical structures in proteins and naturally occurring peptides
      play a major role in a variety of biological processes by mediating interactions
      with proteins and other macromolecules such as nucleic acids and lipid membranes.
      The use of short synthetic peptides encompassing helical segments to modulate or
      disrupt such interactions, when associated with human diseases, represents great
      pharmacological interest. AREAS COVERED: Multiple chemical approaches have been
      developed to increase the conformational and metabolic stabilities of helical
      peptides and to improve their biomedical potential. After a brief overview of
      these technologies and the most recent developments, this review will focus on
      the main therapeutic areas and targets and will discuss their promise. EXPERT
      OPINION: Potential benefits associated with increased helix stability extend
      beyond simple affinity enhancement. Some peptidomimetic helices are being endowed
      with features desirable for cellular activity such as increased resistance to
      proteolysis and/or cell permeability. Recent advances in the field of peptide and
      related peptidomimetic helices are not just conceptual, but are likely to be of
      practical utility in the process of optimizing peptides as clinical candidates,
      and developing medium-size therapeutics.

PMID- 22646217
TI  - Report of the 2nd Chagas Drug Discovery Consortium meeting, held on 3 November
      2010; Atlanta GA, USA.
AB  - Chagas disease is an infectious disease with the highest impact in Latin America
      and a growing worldwide problem. Chagas disease is the result of long-term,
      persistent infection with the protozoan parasite Trypanosoma cruzi. The current
      therapies for treating T. cruzi infection and thus preventing Chagas disease
      often have adverse effects, unpredictable efficacy and require long courses of
      treatment. Development of new therapies has been very limited, in part due to
      lack of interest but also as a result of poor support and inappropriate models
      for discovering and evaluating candidate drugs. The Chagas Drug Discovery
      Consortium (CDDC) was created with funding from the US National Institutes of
      Health to help address some of these issues. The goals of the CDDC are to
      discover and evaluate new candidate drugs and develop rigorous assays of drug
      efficacy. This report summarizes the second meeting of the CDDC in November 2010.

PMID- 22646218
TI  - Binding characteristics of [3H]-JSM10292: a new cell membrane-permeant non
      peptide bradykinin B2 receptor antagonist.
AB  - BACKGROUND AND PURPOSE: A (3) H-labelled derivative of the novel small-molecule
      bradykinin (BK) B(2) receptor antagonist JSM10292 was used to directly study its
      binding properties to human and animal B(2) receptors in intact cells and to
      closely define its binding site. EXPERIMENTAL APPROACH: Equilibrium binding,
      dissociation and competition studies with various B(2) receptor ligands and [(3)
      H]-JSM10292 were performed at 4 degrees C and 37 degrees C. The experiments were
      carried out using HEK293 cells stably (over)expressing wild-type and mutant B(2)
      receptors of human and animal origin. KEY RESULTS: [(3) H]-JSM10292 bound to B(2)
      receptors at 4 degrees C and at 37 degrees C with the same high affinity. Its
      dissociation strongly depended on the temperature and increased when unlabelled
      B(2) receptor agonists or antagonists were added. [(3) H]-JSM10292 is cell
      membrane-permeant and thus also bound to intracellular, active B(2) receptors, as
      indicated by the different 'nonspecific' binding in the presence of unlabelled
      JSM10292 or of membrane-impermeant BK. Equilibrium binding curves with [(3) H]
      JSM10292 and competition experiments with unlabelled JSM10292 and [(3) H]-BK
      showed a different affinity profile for the wild-type B(2) receptor in different
      species (man, cynomolgus, rabbit, mouse, rat, dog, pig, guinea pig).
      Characterization of B(2) receptor mutants and species orthologues combined with
      homology modelling, using the CXCR4 as template, suggests that the binding site
      of JSM10292 is different from that of BK but overlaps with that of MEN16132,
      another small non-peptide B(2) receptor ligand. CONCLUSIONS AND IMPLICATIONS:
      [(3) H]-JSM10292 is a novel, cell membrane-permeant, high-affinity B(2) receptor
      antagonist that allows direct in detail studies of active, surface and
      intracellularly located wild-type and mutant B(2) receptors.

PMID- 22646219
TI  - Effect of desvenlafaxine on mood and climacteric symptoms in menopausal women
      with moderate to severe vasomotor symptoms.
AB  - OBJECTIVE: To assess effects of desvenlafaxine (administered as desvenlafaxine
      succinate) on secondary outcomes of mood, climacteric symptoms, and treatment
      satisfaction in postmenopausal women with moderate to severe menopausal vasomotor
      symptoms (VMS). METHODS: A 12-week, multicenter, double-blind, placebo-controlled
      trial was conducted in postmenopausal women with >= 50 moderate to severe hot
      flushes per week. Participants were randomly assigned to desvenlafaxine 100
      mg/day, desvenlafaxine 150 mg/day, or placebo. Secondary outcome efficacy
      variables included Profile of Mood States (POMS), Greene Climacteric Scale (GCS),
      and Menopausal Symptoms Treatment Satisfaction Questionnaire (MS-TSQ) scores.
      Change from baseline in POMS total mood disturbance (TMD) score and subdomain
      scores were evaluated using analysis of covariance, adjusting for treatment and
      study site as factors and baseline score. GCS total and subdomain scores were
      analyzed similarly. Treatment satisfaction was analyzed using the row mean score
      test. RESULTS: A total of 458 women were enrolled. At week 12, desvenlafaxine 100
      mg/day significantly improved POMS TMD scores (p <0.001) and four of six POMS
      subdomains compared with placebo (all p <= 0.005). Women taking desvenlafaxine
      100 mg/day experienced significantly greater improvement in GCS total scores (p
      <0.001) and five of six subdomains (all p <= 0.029) compared with placebo.
      Treatment with desvenlafaxine 100 mg/day resulted in significantly greater
      treatment satisfaction overall and in six of seven additional MS-TSQ items (all p
      <=0.042). Desvenlafaxine 150-mg/day results were similar. CONCLUSIONS:
      Desvenlafaxine treatment improved mood and climacteric symptoms in postmenopausal
      women with moderate to severe VMS compared with placebo, and more women were
      satisfied with desvenlafaxine treatment than with placebo.

PMID- 22646220
TI  - Barcoding success as a function of phylogenetic relatedness in Viburnum, a clade
      of woody angiosperms.
AB  - BACKGROUND: The chloroplast genes matK and rbcL have been proposed as a "core"
      DNA barcode for identifying plant species. Published estimates of successful
      species identification using these loci (70-80%) may be inflated because they may
      have involved comparisons among distantly related species within target genera.
      To assess the ability of the proposed two-locus barcode to discriminate closely
      related species, we carried out a hierarchically structured set of comparisons
      within Viburnum, a clade of woody angiosperms containing ca. 170 species (some 70
      of which are currently used in horticulture). For 112 Viburnum species, we
      evaluated rbcL + matK, as well as the chloroplast regions rpl32-trnL, trnH-psbA,
      trnK, and the nuclear ribosomal internal transcribed spacer region (nrITS).
      RESULTS: At most, rbcL + matK could discriminate 53% of all Viburnum species,
      with only 18% of the comparisons having genetic distances >1%. When comparisons
      were progressively restricted to species within major Viburnum subclades, there
      was a significant decrease in both the discriminatory power and the genetic
      distances. trnH-psbA and nrITS show much higher levels of variation and potential
      discriminatory power, and their use in plant barcoding should be reconsidered. As
      barcoding has often been used to discriminate species within local areas, we also
      compared Viburnum species within two regions, Japan and Mexico and Central
      America. Greater success in discriminating among the Japanese species reflects
      the deeper evolutionary history of Viburnum in that area, as compared to the
      recent radiation of a single clade into the mountains of Latin America.
      CONCLUSIONS: We found very low levels of discrimination among closely related
      species of Viburnum, and low levels of variation in the proposed barcoding loci
      may limit success within other clades of long-lived woody plants. Inclusion of
      the supplementary barcodes trnH-psbA and nrITS increased discrimination rates but
      were often more effective alone rather than in combination with rbcL + matK. We
      surmise that the efficacy of barcoding in plants has often been overestimated
      because of the lack of comparisons among closely related species. Phylogenetic
      information must be incorporated to properly evaluate relatedness in assessing
      the utility of barcoding loci.

PMID- 22646222
TI  - Mesenchymal stem cells in a polycaprolactone conduit promote sciatic nerve
      regeneration and sensory neuron survival after nerve injury.
AB  - Despite the fact that the peripheral nervous system is able to regenerate after
      traumatic injury, the functional outcomes following damage are limited and poor.
      Bone marrow mesenchymal stem cells (MSCs) are multipotent cells that have been
      used in studies of peripheral nerve regeneration and have yielded promising
      results. The aim of this study was to evaluate sciatic nerve regeneration and
      neuronal survival in mice after nerve transection followed by MSC treatment into
      a polycaprolactone (PCL) nerve guide. The left sciatic nerve of C57BL/6 mice was
      transected and the nerve stumps were placed into a biodegradable PCL tube leaving
      a 3-mm gap between them; the tube was filled with MSCs obtained from GFP+ animals
      (MSC-treated group) or with a culture medium (Dulbecco's modified Eagle's medium
      group). Motor function was analyzed according to the sciatic functional index
      (SFI). After 6 weeks, animals were euthanized, and the regenerated sciatic nerve,
      the dorsal root ganglion (DRG), the spinal cord, and the gastrocnemius muscle
      were collected and processed for light and electron microscopy. A quantitative
      analysis of regenerated nerves showed a significant increase in the number of
      myelinated fibers in the group that received, within the nerve guide, stem cells.
      The number of neurons in the DRG was significantly higher in the MSC-treated
      group, while there was no difference in the number of motor neurons in the spinal
      cord. We also found higher values of trophic factors expression in MSC-treated
      groups, especially a nerve growth factor. The SFI revealed a significant
      improvement in the MSC-treated group. The gastrocnemius muscle showed an increase
      in weight and in the levels of creatine phosphokinase enzyme, suggesting an
      improvement of reinnervation and activity in animals that received MSCs.
      Immunohistochemistry documented that some GFP+ -transplanted cells assumed a
      Schwann-cell-like phenotype, as evidenced by their expression of the S-100
      protein, a Schwann cell marker. Our findings suggest that using a PCL tube filled
      with MSCs is a good strategy to improve nerve regeneration after a nerve
      transection in mice.

PMID- 22646223
TI  - A direct SAXS approach for the determination of specific surface area of clay in
      polymer-layered silicate nanocomposites.
AB  - The interfacial area between the matrix and the filler is a key parameter which
      shapes the performance of polymer-based composites and nanocomposites, even
      though it is difficult to quantify. A very easy SAXS method, based on the Porod
      equation, is proposed for measuring the specific surface area of nanofillers
      embedded in a polymer matrix. In order to assess its reliability, this approach
      was applied to natural rubber- or styrene butadiene-based samples containing
      different types of montmorillonite clay. A wide range of specific surfaces was
      detected. SAXS data were compared to complementary X-ray diffraction and TEM
      information, obtaining a good agreement. Interpretation of the tensile properties
      by theoretical models and comparison with the literature corroborated the
      validity of the specific surface area measurement. The possibility to quantify
      this feature of composites allows the rational design of such materials to be
      improved.

PMID- 22646221
TI  - Discovery, structure-activity relationship, and biological evaluation of
      noninhibitory small molecule chaperones of glucocerebrosidase.
AB  - A major challenge in the field of Gaucher disease has been the development of new
      therapeutic strategies including molecular chaperones. All previously described
      chaperones of glucocerebrosidase are enzyme inhibitors, which complicates their
      clinical development because their chaperone activity must be balanced against
      the functional inhibition of the enzyme. Using a novel high throughput screening
      methodology, we identified a chemical series that does not inhibit the enzyme but
      can still facilitate its translocation to the lysosome as measured by
      immunostaining of glucocerebrosidase in patient fibroblasts. These compounds
      provide the basis for the development of a novel approach toward small molecule
      treatment for patients with Gaucher disease.

PMID- 22646227
TI  - An Interview with Lauren Broyles, PhD, RN, Nurse Researcher. Interview by Joan
      Kub.

PMID- 22646229
TI  - Facile method for the preparation of water dispersible graphene using sulfonated
      poly(ether-ether-ketone) and its application as energy storage materials.
AB  - A simple and effective method for the preparation of water dispersible graphene
      using sulfonated poly(ether-ether-ketone) (SPEEK) has been described. The SPEEK
      macromolecules are noncovalently adsorbed on the surface of graphene through pi
      pi interactions. The SPEEK-modified graphene (SPG) forms an aqueous dispersion
      that is stable for more than six months. An analysis of the ultraviolet-visible
      spectra shows that the aqueous dispersion of SPG obeys Beer's law and the molar
      extinction coefficient has been found to be 149.03 mL mg(-1) cm(-1). Fourier
      transform infrared, Raman, and X-ray photoelectron spectroscopy analyses confirm
      successful reduction and surface modification of graphene. An atomic force
      microscopy (AFM) analysis reveals the formation of a single layer of
      functionalized graphene. Transmission electron microscopy results are also in
      good agreement with the AFM analysis and support the formation of single-layer
      graphene. SPG shows good electrochemical cyclic stability during cyclic
      voltammetry and charge/discharge process when used as a supercapacitor electrode.
      A specific capacitance of 476 F g(-1) at a current density of 6.6 A g(-1) is
      observed for SPG materials.

PMID- 22646228
TI  - Comparative genome analysis of 19 Ureaplasma urealyticum and Ureaplasma parvum
      strains.
AB  - BACKGROUND: Ureaplasma urealyticum (UUR) and Ureaplasma parvum (UPA) are sexually
      transmitted bacteria among humans implicated in a variety of disease states
      including but not limited to: nongonococcal urethritis, infertility, adverse
      pregnancy outcomes, chorioamnionitis, and bronchopulmonary dysplasia in neonates.
      There are 10 distinct serotypes of UUR and 4 of UPA. Efforts to determine whether
      difference in pathogenic potential exists at the ureaplasma serovar level have
      been hampered by limitations of antibody-based typing methods, multiple cross
      reactions and poor discriminating capacity in clinical samples containing two or
      more serovars. RESULTS: We determined the genome sequences of the American Type
      Culture Collection (ATCC) type strains of all UUR and UPA serovars as well as
      four clinical isolates of UUR for which we were not able to determine serovar
      designation. UPA serovars had 0.75-0.78 Mbp genomes and UUR serovars were 0.84
      0.95 Mbp. The original classification of ureaplasma isolates into distinct
      serovars was largely based on differences in the major ureaplasma surface antigen
      called the multiple banded antigen (MBA) and reactions of human and animal sera
      to the organisms. Whole genome analysis of the 14 serovars and the 4 clinical
      isolates showed the mba gene was part of a large superfamily, which is a phase
      variable gene system, and that some serovars have identical sets of mba genes.
      Most of the differences among serovars are hypothetical genes, and in general the
      two species and 14 serovars are extremely similar at the genome level.
      CONCLUSIONS: Comparative genome analysis suggests UUR is more capable of
      acquiring genes horizontally, which may contribute to its greater virulence for
      some conditions. The overwhelming evidence of extensive horizontal gene transfer
      among these organisms from our previous studies combined with our comparative
      analysis indicates that ureaplasmas exist as quasi-species rather than as stable
      serovars in their native environment. Therefore, differential pathogenicity and
      clinical outcome of a ureaplasmal infection is most likely not on the serovar
      level, but rather may be due to the presence or absence of potential
      pathogenicity factors in an individual ureaplasma clinical isolate and/or patient
      to patient differences in terms of autoimmunity and microbiome.

PMID- 22646231
TI  - Quantifying population structure on short timescales.
AB  - Quantifying the contribution of the various processes that influence population
      genetic structure is important, but difficult. One of the reasons is that no
      single measure appropriately quantifies all aspects of genetic structure. An
      increasing number of studies is analysing population structure using the
      statistic D, which measures genetic differentiation, next to G(ST) , which
      quantifies the standardized variance in allele frequencies among populations. Few
      studies have evaluated which statistic is most appropriate in particular
      situations. In this study, we evaluated which index is more suitable in
      quantifying postglacial divergence between three-spined stickleback (Gasterosteus
      aculeatus) populations from Western Europe. Population structure on this short
      timescale (10 000 generations) is probably shaped by colonization history,
      followed by migration and drift. Using microsatellite markers and anticipating
      that D and G(ST)  might have different capacities to reveal these processes, we
      evaluated population structure at two levels: (i) between lowland and upland
      populations, aiming to infer historical processes; and (ii) among upland
      populations, aiming to quantify contemporary processes. In the first case, only D
      revealed clear clusters of populations, putatively indicative of population
      ancestry. In the second case, only G(ST)  was indicative for the balance between
      migration and drift. Simulations of colonization and subsequent divergence in a
      hierarchical stepping stone model confirmed this discrepancy, which becomes
      particularly strong for markers with moderate to high mutation rates. We conclude
      that on short timescales, and across strong clines in population size and
      connectivity, D is useful to infer colonization history, whereas G(ST)  is
      sensitive to more recent demographic events.

PMID- 22646230
TI  - Severe hypoglycemia symptoms, antecedent behaviors, immediate consequences and
      association with glycemia medication usage: Secondary analysis of the ACCORD
      clinical trial data.
AB  - BACKGROUND: Hypoglycemia is a common complication of diabetes treatment. This
      paper describes symptoms, predecessors, consequences and medications associated
      with the first episode of severe hypoglycemia among ACCORD participants with type
      2 diabetes, and compares these between intensive (Int: goal A1C <6.0%) and
      standard (Std, goal A1C 7-7.9%) glycemia intervention groups. METHODS:
      Information about symptoms, antecedents, and consequences was collected at the
      time participants reported an episode of severe hypoglycemia. Data on medications
      prescribed during the clinical trial was used to determine the association of
      particular diabetes drug classes and severe hypoglycemia. RESULTS: The most
      frequently reported symptoms in both glycemia group were weakness/fatigue (Int
      29%; Std 30%) and sweating (Int 26%; Std 27%), followed by
      confusion/disorientation (Int 22%; Std 29%) and shakiness (Int 21%; Std 19%).
      Approximately half of all events were preceded by a variation in food intake (Int
      48%; Std 58%). The most common consequences were confusion (Int 37%; Std 34%),
      loss of consciousness (Int 25%; Std 25%), and hospitalization (Int 18%; Std 24%).
      The highest rates of hypoglycemia were found among those participants treated
      with insulin only (Int 6.09/100 person yrs; Std 2.64/100 person yrs) while the
      lowest were among those prescribed oral agents only (Int 1.93/100 person yrs; Std
      0.20/100 person yrs). CONCLUSIONS: Severe hypoglycemia episodes were frequently
      preceded by a change in food intake, making many episodes potentially
      preventable. Symptoms of confusion/disorientation and loss of consciousness were
      frequently seen. The highest rates of hypoglycemia were seen with prescription of
      insulin, either alone or in combination with other medications. CLINICAL TRIAL
      REGISTRATION: Number: NCT00000620.

PMID- 22646232
TI  - Facile photochemical synthesis of graphene-pt nanoparticle composite for counter
      electrode in dye sensitized solar cell.
AB  - A low temperature route to synthesize graphene oxide-Pt nanoparticle hybrid
      composite by light assisted spontaneous coreduction of graphene oxide and
      chloroplatinic acid without reducing agent is demonstrated. Analysis indicates
      the importance of light as energy provider and ethanol as hole scavenger in the
      formation of small Pt nanoparticles (~3 nm) on graphene oxide as well as graphene
      oxide reduction. Spray coating was used to deposit the hybrid material as a
      counter electrode in dye sensitized solar cells (DSCs). An efficiency of 6.77%
      for the hybrid graphene counter electrode has been obtained, higher than the
      control device made by low temperature sputtered Pt as counter electrode.
      Compatibility of the hybrid material with flexible plastic substrates was
      demonstrated yielding DSCs of an efficiency of 4.05%. 

PMID- 22646234
TI  - Fitness-compensatory mutations in rifampicin-resistant RNA polymerase.
AB  - Mutations in rpoB (RNA polymerase beta-subunit) can cause high-level resistance
      to rifampicin, an important first-line drug against tuberculosis. Most rifampicin
      resistant (Rif(R)) mutants selected in vitro have reduced fitness, and resistant
      clinical isolates of M. tuberculosis frequently carry multiple mutations in RNA
      polymerase genes. This supports a role for compensatory evolution in global
      epidemics of drug-resistant tuberculosis but the significance of secondary
      mutations outside rpoB has not been demonstrated or quantified. Using Salmonella
      as a model organism, and a previously characterized Rif(R) mutation (rpoB R529C)
      as a starting point, independent lineages were evolved with selection for
      improved growth in the presence and absence of rifampicin. Compensatory mutations
      were identified in every lineage and were distributed between rpoA, rpoB and
      rpoC. Resistance was maintained in all strains showing that increased fitness by
      compensatory mutation was more likely than reversion. Genetic reconstructions
      demonstrated that the secondary mutations were responsible for increasing growth
      rate. Many of the compensatory mutations in rpoA and rpoC individually caused
      small but significant reductions in susceptibility to rifampicin, and some
      compensatory mutations in rpoB individually caused high-level resistance. These
      findings show that mutations in different components of RNA polymerase are
      responsible for fitness compensation of a Rif(R) mutant.

PMID- 22646233
TI  - Monozygotic twins concordant for Kleine-Levin syndrome.
AB  - BACKGROUND: Kleine-Levin syndrome is a rare sleep disorder of unknown etiology.
      It is characterized by intermittent periods of excessive sleepiness, cognitive
      disturbances and behavioral abnormalities. Nine cases of familial Kleine-Levin
      syndrome have been identified, but there are no reported cases describing twins
      that are affected by the syndrome. CASE PRESENTATION: We report the cases of 16
      year-old monozygotic twin boys who both suffered from Kleine-Levin syndrome. In
      both cases, the onset of the first episode was preceded by an influenza
      infection. During symptomatic periods they slept for the entire day except for
      meals and bathroom visits. Actimetry recordings revealed that during symptomatic
      periods, daily activity was lower than that of asymptomatic periods, on the other
      hand, activity during the night was significantly higher in symptomatic periods
      than asymptomatic periods. Polysomnography (PSG) data during symptomatic periods
      revealed a decrease in sleep efficiency. Human leukocyte antigen (HLA) typing
      revealed no DQB1*02 loci. They were administered lithium carbonate but the
      beneficial effect was limited. CONCLUSIONS: Our observations suggest that Kleine
      Levin syndrome may be due to genetic and autoimmune processes, although etiologic
      relationship to specific HLA type remains controversial.

PMID- 22646235
TI  - A comprehensive 4-year survey of adverse drug reactions using a network-based
      hospital system.
AB  - WHAT IS KNOWN AND OBJECTIVE: Spontaneous Adverse Drug Reaction Reporting Systems
      (ADRRS) provide early warnings or 'signals' for adverse drug reactions (ADRs).
      Our aim was to survey reports of ADRs made through our teaching-hospital-based
      pharmacovigilance system to identify the drugs most commonly associated with
      allergies and the types of immunological reactions reported. METHODS: Adverse
      drug reactions records were retrieved from our network-based electronic
      notification system. RESULTS AND DISCUSSION: Four hundred and seventy four
      reports of adverse drug effects were studied. 37.3% of the reactions were immune
      mediated drug hypersensitivity reactions. True drug hypersensitivity reactions
      involving IgE-mediated drug allergies accounted for 15% of all reactions. Of the
      drug hypersensitivity reactions, more than half (67%) were morbilliform skin
      eruptions, whereas cases of urticaria accounted for 20%. Antibiotics (33% of
      cases) were the most commonly reported drug allergies, followed by non-steroidal
      anti-inflammatory drugs (13%) and anti-epileptic agents (10%). WHAT IS NEW AND
      CONCLUSIONS: A hospital-based ADR reporting system can generate useful data. In
      our study, antibiotics accounted for the majority of drug allergies, particularly
      anaphylactic reactions. More cases of drug allergies were owing to cephalosporin
      allergies than penicillins. Anti-epileptic agents caused most of the severe drug
      hypersensitivity syndromes.

PMID- 22646236
TI  - The incidence, clinical features, and treatment of type 2 diabetes in children
      <15 yr in a population-based cohort from Auckland, New Zealand, 1995-2007.
AB  - BACKGROUND: The incidence of type 2 diabetes mellitus (T2DM) is increasing in
      adolescents in most western countries. The time-course of glycemic control and
      impact of early treatment remain poorly understood. OBJECTIVES: To determine the
      change in incidence of T2DM, and the time-course of glycemic control in a
      regional pediatric cohort with T2DM. METHODS: Retrospective analysis of
      prospectively collected data on 52 patients with T2DM from a population-based
      treatment referral cohort from 1 January 1995 to 31 December 2007. RESULTS: The
      annual incidence of new cases of T2DM in children <15 yr increased fivefold in
      the Auckland region of New Zealand from 1995 [0.5/100,000; 95% confidence
      interval (CI) 0.0-2.2] to 2007 (2.5/100,000; 95% CI 1.0-5.5). The average annual
      incidence per 100,000 over the entire period was 1.3 (95% CI 1.0-1.8) overall,
      0.1 (0.0-0.4) in Europeans, and 3.4 in both Maori (2.0-5.3) and Pacifica (2.2
      5.0). Fifty-seven percent of children were symptomatic at presentation. Fifty
      eight percent of patients were treated with insulin from diagnosis, most of whom
      were symptomatic (p = 0.003). Follow-up data were available for 48 patients with
      a mean of 2.4 yr. Although insulin therapy was associated with a greater fall in
      HbA1c values in the first 12 months of treatment (to a nadir of 7.1 vs. 8.1%, p <
      0.05), there was a rapid deterioration after 12 months, and subsequent mean HbA1c
      values were >9% in both groups. Therapy did not affect body mass index standard
      deviation score (BMI SDS). CONCLUSIONS: The incidence of T2DM in childhood or
      adolescence increased markedly over a 13-yr period in the Auckland region. Long-

PMID- 22646237
TI  - Long-term follow-up of concomitant treatment with romiplostim and warfarin in a
      patient with immune thrombocytopenia and severe cardiac comorbidities.

PMID- 22646238
TI  - Systematic evolution from uranyl(VI) phosphites to uranium(IV) phosphates.
AB  - Six new uranium phosphites, phosphates, and mixed phosphate-phosphite compounds
      were hydrothermally synthesized, with an additional uranyl phosphite synthesized
      at room temperature. These compounds can contain U(VI) or U(IV), and two are
      mixed-valent U(VI)/U(IV) compounds. There appears to be a strong correlation
      between the starting pH and reaction duration and the products that form. In
      general, phosphites are more likely to form at shorter reaction times, while
      phosphates form at extended reaction times. Additionally, reduction of uranium
      from U(VI) to U(IV) happens much more readily at lower pH and can be slowed with
      an increase in the initial pH of the reaction mixture. Here we explore the in
      situ hydrothermal redox reactions of uranyl nitrate with phosphorous acid and
      alkali-metal carbonates. The resulting products reveal the evolution of compounds
      formed as these hydrothermal redox reactions proceed forward with time.

PMID- 22646239
TI  - Identification of CHD7S as a novel splicing variant of CHD7 with functions
      similar and antagonistic to those of the full-length CHD7L.
AB  - CHD7 is one of the nine members of the chromodomain helicase DNA-binding family
      of ATP-dependent chromatin remodeling enzymes. Mutations in CHD7 give rise to
      CHARGE syndrome, a human condition characterized by malformation of various
      organs. We have now identified a novel transcript of CHD7 that is generated by
      alternative splicing of exon 6. The protein encoded by this variant transcript
      (termed CHD7S) lacks one of the two chromodomains as well as the helicase/ATPase
      domain, DNA-binding domain and BRK domains of the full-length protein (CHD7L).
      CHD7S was found to localize specifically to the nucleolus in a manner dependent
      on a nucleolar localization signal. Over-expression of CHD7S, as well as that of
      CHD7L, resulted in an increase in 45S precursor rRNA production. Conversely,
      depletion of both CHD7S and CHD7L by RNA interference inhibited both 45S
      precursor rRNA production and cell proliferation to a greater extent than did
      depletion of CHD7L alone. Furthermore, we found that, like CHD7L, CHD7S binds to
      Sox2 in the nucleoplasm. Unexpectedly, however, whereas over-expression of CHD7L
      promoted Sox2-mediated transcriptional regulation, over-expression of CHD7S
      suppressed it. These results indicate that CHD7S functions cooperatively or
      antagonistically with CHD7L in the nucleolus and nucleoplasm, respectively.

PMID- 22646240
TI  - Effects of prasugrel on platelet inhibition during systemic endotoxaemia: a
      randomized controlled trial.
AB  - P2Y(12) receptor antagonists have become a mainstay for the treatment of CVD
      (cardiovascular diseases). However, they have rarely been evaluated under
      pathophysiological conditions apart from arterial diseases. We hypothesized
      interactions between prasugrel and enhanced vWF (von Willebrand Factor) release
      in a model of systemic inflammation, and compared the pharmacodynamic effects of
      prasugrel against placebo on agonist-induced platelet aggregation and shear
      induced platelet plug formation. A total of 20 healthy male volunteers were
      enrolled in a double-blind placebo-controlled two-way crossover trial. Each
      volunteer received either placebo or a 60 mg loading dose of prasugrel 2 h before
      endotoxin or placebo infusion. Platelet inhibition was measured with MEA
      (multiple electrode aggregometry), the PFA-100 system and the VASP (vasodilator
      stimulated phosphoprotein) phosphorylation assay. Prasugrel blunted various
      platelet aggregation pathways, including those induced by ADP (-81%), AA
      (arachidonic acid) (-60%), ristocetin (-75%; P<0.001 for all) and, to a lesser
      degree, collagen or TRAP (thrombin-receptor-activating peptide). Prasugrel
      decreased shear-induced platelet plug formation, but vWF release during
      endotoxaemia partly antagonized the inhibitory effect of prasugrel as measured
      with the PFA-100 system. Endotoxaemia acutely decreased ristocetin and TRAP
      induced platelet aggregation, and enhanced ristocetin-induced aggregation after
      24 h. Strong in vivo blockade of P2Y(12) inhibits a broad spectrum of platelet
      aggregation pathways. However, vWF release may reduce prasugrel's effects under
      high-shear conditions.

PMID- 22646241
TI  - Evaluation of a quality-of-life tool for dogs with diabetes mellitus.
AB  - BACKGROUND: Diabetes mellitus (DM) management primarily focuses on improvement in
      blood glucose concentrations and clinical signs. A tool to assess the
      psychological and social impact of DM and its treatment on quality of life (QoL)
      previously has only been validated for feline DM. HYPOTHESIS/OBJECTIVES: To
      validate a diabetic pet and owner-centered individualized measure of impact of DM
      (DIAQoL-pet) for diabetic dogs and their owners. ANIMALS/SUBJECTS: A total of 101
      owners of insulin-treated diabetic dogs were recruited to complete the DIAQoL
      pet. METHODS: Discussions and pilot surveys with clinicians and owners of
      diabetic pets led to the design of 29 specific DM-associated QoL questions. Each
      item was scored according to impact frequency and perceived importance. An Item
      Weighted-Impact-Score (IWIS) for each item was calculated, as was an Average
      Weighted-Impact-Score (AWIS) by averaging all IWISs. Principal component analysis
      and Cronbach's alpha calculation assessed the measure's reliability. RESULTS: The
      DIAQoL-pet showed high reliability (Communalities >=0.5; Cronbach's alpha 0.85).
      The AWIS was -2.74 +/- 1.7 (mean +/- SD). Areas reported as most negatively
      impacting QoL included: "worry" (IWIS +/- SD: -5.92 +/- 4.3), "difficulties
      leaving dog with friends or family" (-5.68 +/- 5.1), "worry vision" (-5.58 +/-
      4.6), "boarding difficulties" (-5.18 +/- 5.2), "worry hypoglycemia" (-4.95 +/-
      4.3), "social life" (-4.82 +/- 4.4), "costs" (-4.11 +/- 4.7), and "future care"(
      4.07 +/- 4.6). Eighty-four percent of owners reported negative impact of DM on
      QoL. CONCLUSIONS AND CLINICAL IMPORTANCE: The DIAQoL-pet proved robust when used
      by owners of insulin-treated diabetic dogs and identified specific areas most
      negatively impacting dogs' and their owners' QoL. This tool could be used as an
      additional assessment parameter in clinical and research settings.

PMID- 22646242
TI  - Cell preparation method with trypsin digestion for counting of colony forming
      units in Candida albicans-infected mucosal tissues.
AB  - Colony forming units (CFU) of Candida albicans in cell suspensions or homogenates
      prepared from C. albicans-infected tissues are not always accurate indicators of
      the severity of infection in mucosal tissues. In order to improve the reliability
      of CFU counts in the murine oral candidiasis model, we developed a new cell
      preparation method in which a dispersal process involving trypsin digestion was
      included in the processing of Candida albicans-infected tongue tissues. Trypsin
      digestion, which was added to the conventional method for preparing Candida
      suspension from tongue homogenates, improved the recovery yield as evidenced by
      an increase in Candida CFU's. This method also increased the number of planktonic
      Candida cells which could pass through a mesh filter, perhaps because the trypsin
      contributed to the break up of the complex mass of tissue-debris and C.albicans
      cells. Using this trypsin digestion technique, we confirmed the protective action
      of farnesol by a relative decrease in the number of viable Candida cells in
      homogenates of infected tongues, which was correlated with improvement of the
      symptoms of oral candidiasis. These results indicate that our new method of
      trypsin digestion is valuable in that it reflects the protective activity of some
      bioactive substances against mucosal candidiasis.

PMID- 22646243
TI  - Blastomycosis in India: report of an imported case and current status.
AB  - We report a case of disseminated blastomycosis in a female resident of Delhi, who
      acquired the infection during travel to the USA, which was successfully treated
      with oral itraconazole. In addition, we present a critical literature review,
      indicating that blastomycosis is endemic in India but its areas of endemicity,
      prevalence, and the natural habitat of the etiologic agent, remain undetermined.
      The diagnosis of blastomycosis was made by examination of Gomori's methenamine
      silver stained sections of tissue obtained from a biopsy of a subcutaneous,
      abdominal nodular. These studies revealed thick-walled, broad-based budding yeast
      cells compatible with Blastomyces dermatitidis, and consistent with the isolation
      of the fungus in cultures inoculated with posterior auricular lymph node
      aspirate. Microscopically, the isolate had thin, septate hyphae and
      characteristic spherical to pyriform, smooth-walled microconidia. Its identity
      was confirmed by conversion to its typical yeast form on pea seed agar at 37
      degrees C and by DNA sequencing of ITS and BAD 1 promoter regions.

PMID- 22646244
TI  - Up-regulation of antioxidants in tobacco by low concentrations of H2O2 suppresses
      necrotic disease symptoms.
AB  - Pretreatment of tobacco leaves with low concentrations (5 to 10 mM) of H2O2
      suppressed hypersensitive-type necrosis associated with resistance to Tobacco
      mosaic virus (TMV) or Pseudomonas syringae pv. phaseolicola. The same
      pretreatment resulted in suppression of normosensitive necrosis associated with
      susceptibility to Botrytis cinerea. This type of H2O2-mediated, induced disease
      symptom resistance correlated with enhanced host antioxidant capacity, i.e.,
      elevated enzymatic activities of catalase (CAT), ascorbate peroxidase (APX), and
      guaiacol peroxidase (POX) after viral and bacterial infections. Induction of
      genes that encode the antioxidants superoxide dismutase (SOD), CAT, and APX was
      also enhanced early after TMV infection. Artificial application of SOD and CAT
      suppressed necroses caused by viral, bacterial, or fungal pathogens similarly as
      H2O2 pretreatment, implying that H2O2-mediated symptom resistance operates
      through enhancement of plant antioxidant capacity. Pathogen multiplication was
      not significantly affected in H2O2-pretreated plants. Salicylic acid (SA), a
      central component of plant defense, does not seem to function in this type of
      H2O2-mediated symptom resistance, indicated by unchanged levels of free and bound
      SA and a lack of early up-regulation of an SA glucosyltransferase gene in TMV
      infected H2O2-pretreated tobacco. Taken together, H2O2-mediated, induced
      resistance to necrotic symptoms in tobacco seems to depend on enhanced
      antioxidant capacity.

PMID- 22646245
TI  - Dynamics of phenanthrenequinone on carbon nano-onion surfaces probed by
      quasielastic neutron scattering.
AB  - We used quasielastic neutron scattering (QENS) to study the dynamics of
      phenanthrenequinone (PQ) on the surface of onion-like carbon (OLC), or so-called
      carbon onions, as a function of surface coverage and temperature. For both the
      high- and low-coverage samples, we observed two diffusion processes; a faster
      process and nearly an order of magnitude slower process. On the high-coverage
      surface, the slow diffusion process is of long-range translational character,
      whereas the fast diffusion process is spatially localized on the length scale of
      ~4.7 A. On the low-coverage surface, both diffusion processes are spatially
      localized; on the same length scale of ~4.7 A for the fast diffusion and a
      somewhat larger length scale for the slow diffusion. Arrhenius temperature
      dependence is observed except for the long-range diffusion on the high-coverage
      surface. We attribute the fast diffusion process to the generic localized in-cage
      dynamics of PQ molecules, and the slow diffusion process to the long-range
      translational dynamics of PQ molecules, which, depending on the coverage, may be
      either spatially restricted or long-range. On the low-coverage surface, uniform
      surface coverage is not attained, and the PQ molecules experience the effect of
      spatial constraints on their long-range translational dynamics. Unexpectedly, the
      dynamics of PQ molecules on OLC as a function of temperature and surface coverage
      bears qualitative resemblance to the dynamics of water molecules on oxide
      surfaces, including practically temperature-independent residence times for the
      low-coverage surface. The dynamics features that we observed may be universal
      across different classes of surface adsorbates.

PMID- 22646247
TI  - Primary sclerosing cholangitis: providing a safe and effective treatment.

PMID- 22646246
TI  - H. pylori clinical isolates have diverse babAB genotype distributions over
      different topographic sites of stomach with correlation to clinical disease
      outcomes.
AB  - BACKGROUND: Intragenomic recombination between babA and babB mediates antigenic
      variations and may help H. pylori colonization. This study determined whether
      variable genotypes of babA and babB correlate to different clinical disease
      outcomes, and can distribute over the different gastric niches. RESULTS: This
      study enrolled 92 clinical strains (45 from peptic ulcer, 27 from gastritis, and
      20 from gastric cancer) to detect whether the babA and babB are at locus A or B
      by PCR reactions using the primers designed from the upstream and variable region
      of the babA and babB genes. Four genotypes of babA and babB (A B, AB B, A AB, AB
      AB) were found. The distribution of the 4 genotypes in 92 clinical strains was
      significantly different among patients with different gastric diseases (p <
      0.05). The isolates from gastric cancer patients had a higher rate of AB AB
      genotype than those from non-cancer patients (40.0% vs. 9.7%, p < 0.05). The AB
      AB genotype was associated with a higher intensity of intestinal metaplasia (p <
      0.05), but did not correlate with a higher inflammation and colonization density
      in gastric histology (p > 0.05). Besides, the study enrolled 19 patients to
      verify whether variable genotypes of babAB existed in the different gastric
      niches. Among the patients infected with more than one babAB genotypes over
      antrum and corpus, there were higher rate of genotypes as A B or AB AB in
      isolates from antrum than in those from corpus (75.0 % vs. 16.7%, p < 0.05).
      CONCLUSIONS: The H. pylori isolate with the AB AB genotype correlates with an
      increased gastric cancer risk, and colonize in an antrum predominant manner.

PMID- 22646250
TI  - Effect of ethnicity on the clinical presentation and outcome of autoimmune
      hepatitis.
AB  - Autoimmune hepatitis (AIH) is a progressive inflammatory disorder affecting
      children and adults of both sexes. Although AIH is known to occur in all
      geographical areas, racial differences have not been studied systematically. The
      paper by Wong et al. reports a retrospective study analyzing AIH epidemiology
      among ethnically different populations referred to a tertiary-care hospital. A
      total of 183 patients were included and divided according to their ethnicity into
      Hispanic, Asian and Caucasian groups. Age at diagnosis and sex distribution was
      similar in all three groups. Compared with Caucasians, Asian patients had a
      higher international normalized ratio, whereas, in addition to higher
      international normalized ratio, Hispanics also showed lower levels of albumin and
      platelets, as well as higher prevalence of biopsy-proven cirrhosis at
      presentation. Despite this, Kaplan-Meier analysis showed that Hispanics had the
      best survival outcomes, followed by Caucasians. Asians had the poorest survival
      outcome.

PMID- 22646248
TI  - Focusing on the patient: impact of new UK guidelines on treatment of chronic
      hepatitis C.

PMID- 22646251
TI  - Reducing complications in upper gastrointestinal endoscopy.
AB  - This article reviews the principal aspects related to sedation in endoscopy and
      to the prevention of adverse events in some of the most frequently performed
      therapeutic upper gastrointestinal (GI) endoscopic procedures (esophageal
      dilation and stenting, endoscopic resection of upper GI early neoplasia,
      hemostasis of upper GI bleeding and percutaneous endoscopic gastrostomy
      insertion). These procedures have an inherent risk of negative outcomes that
      cannot be entirely avoided. Endoscopic procedures are best performed by well
      trained, competent and thoughtful endoscopists in facilities suited to provide
      for patient safety. Attention to clinical risk management may effectively reduce
      the frequency and intensity of adverse events, enhance recognition and early
      detection, and improve responsiveness.

PMID- 22646252
TI  - Endoscopic therapies for Barrett's-associated dysplasia: a new paradigm for a new
      decade.
AB  - The emergence of endoscopic therapies for Barrett's esophagus (BE)-associated
      dysplasia has significantly altered the management of this complex disease. Over
      the past decade, there has been a paradigm shift from that of pure surveillance
      to a more therapeutic approach in eradicating dysplastic BE. This strategy
      includes less invasive options than esophagectomy for high-grade dysplasia and
      early eradication of confirmed low-grade dysplasia. Although multiple modalities
      exist for endoscopic therapy, endoscopic mucosal resection coupled with
      radiofrequency ablation appears to be the most effective therapy, with minimal
      complications. Recent advances in endoscopic eradication therapies for dysplastic
      BE have fueled excitement for a significant weapon against the rising incidence
      of esophageal cancer.

PMID- 22646253
TI  - Screening for colorectal cancer: what fits best?
AB  - Colorectal cancer (CRC) screening has been shown to be effective in reducing CRC
      incidence and mortality. There are currently a number of screening modalities
      available for implementation into a population-based CRC screening program. Each
      screening method offers different strengths but also possesses its own
      limitations as a population-based screening strategy. We review the current
      evidence base for accepted CRC screening tools and evaluate their merits
      alongside their challenges in fulfilling their role in the detection of CRC. We
      also aim to provide an outlook on the demands of a low-risk population-based CRC
      screening program with a view to providing insight as to which modality would
      best suit current and future needs.

PMID- 22646254
TI  - Chromogranin A: a sensitive biomarker for the detection and post-treatment
      monitoring of gastroenteropancreatic neuroendocrine tumors.
AB  - Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are a heterogeneous group
      of neoplasms that arise from neuroendocrine cells of the GI tract and pancreas.
      Due to the lack of symptoms in the early stage of the disease and the frequency
      of nonspecific gastrointestinal symptoms, GEP-NET are difficult to diagnose. This
      delay in diagnosis often results in patients presenting with advanced disease and
      thus a poor prognosis. There is an unmet medical need for earlier, more
      definitive GEP-NET diagnosis. Identification of effective biomarkers to improve
      GEP-NET diagnosis, as well as to assess treatment efficacy, relapse and
      prognosis, is important for improving outcomes in GEP-NET. Chromogranin A is
      currently the most useful general biomarker for the assessment of GEP-NET. This
      review summarizes the biochemical characteristics of chromogranin A, its
      specificity and sensitivity for GEP-NET diagnosis, and its use in monitoring
      treatment effectiveness, disease progression and prognosis.

PMID- 22646255
TI  - Understanding the genetic basis of gastric cancer: recent advances.
AB  - Two major gastric cancer histological subtypes are recognized with distinct
      morphology, epidemiology, pathogenesis and clinical behavior. Genetically, the
      intestinal and diffuse subtypes are also characterized by distinct germline
      susceptibility patterns and somatic aberrations. Helicobacter pylori is strongly
      associated with both Lauren's subtypes, although the underlying carcinogenic
      mechanisms are unique. Risk is modulated by strain-specific virulence factors,
      host responses and specific host-microbe interactions. Somatic aberrations in
      gastric cancer are driven by three major mechanisms, namely chromosomal
      instability, microsatellite instability and epigenetic alterations. These
      processes drive carcinogenesis in both Lauren's subtypes; however, the relative
      contribution of these processes and the specific genes aberrated differ. Moving
      beyond Lauren's subtypes, next-generation techniques have identified major
      genomic subtypes that have prognostic impact and exhibit distinct response
      patterns to standard cytotoxics.

PMID- 22646256
TI  - Nanotechnology advances in upper gastrointestinal, liver and pancreatic cancer.
AB  - Cancers of the upper GI tract, liver and pancreas have some of the poorest
      prognoses of any malignancies. Advances in diagnosis and treatment are sorely
      needed to improve the outcomes of patients. Nanotechnology offers the potential
      for constructing tailor-made therapies capable of targeting specific cancers. The
      particles themselves may be endowed with multifunctional properties that can be
      exploited for both diagnosis and treatment. Although development of therapies is
      still in the early stages, the use of nanoparticles (NPs) is widespread in
      diagnostic applications and will probably involve all areas of medicine in the
      future. Research into NPs is ongoing for upper gastrointestinal, liver and
      pancreatic cancers, and their use is becoming increasingly popular as contrast
      media for radiological investigations. Although more sophisticated technologies
      capable of active targeting are still in the early stages of assessment for
      clinical use, a small number of NP-based therapies are in clinical use.

PMID- 22646257
TI  - Treatment options for unresectable neuroendocrine liver metastases.
AB  - Hepatic metastases develop in 85% of patients with gastroenteropancreatic
      neuroendocrine tumors. Radical surgery, which involves resection of the primary
      and liver metastases, is the mainstay of treatment, with 60-70% 5-year survival
      and 35% 10-year survival rates. However, less than 15% of neuroendocrine tumor
      liver metastases (NETLMs) are resectable, owing either to multifocality or the
      inability to preserve sufficient parenchyma following resection. This article
      deals with the therapeutic modalities available for nonresectable liver
      metastases, and the therapeutic options available for management of nonresectable
      NETLMs are discussed. Targeted therapies for NETLMs include hepatic artery
      embolization, transcatheter arterial chemoembolization, radiolabeled/drug-eluting
      microspheres, radiofrequency ablation, cryoablation and phenol injection. Hepatic
      artery embolization/transcatheter arterial chemoembolization is associated with
      75-100% symptom relief and an objective tumor response varying from 33 to 80%.
      Other modalities, such as biotherapy, peptide receptor therapy and chemotherapy,
      target both the primary and metastatic disease. Their effects on NETLMs as a
      subgroup have not been evaluated. Various therapeutic options are available for
      the treatment of unresectable NETLMs. Most offer significant symptomatic relief,
      with only a few comparative studies showing survival benefit. Most of the
      available evidence is based on retrospective and prospective case series rather
      than randomized controlled trials. Well-designed studies on existing treatment
      modalities and the search for newer therapeutic options are required.

PMID- 22646258
TI  - Basic answers to complicated questions for the course of chronic hepatitis C
      treatment.
AB  - Hepatitis C virus infection is a long-lasting disease, which causes chronic
      hepatitis, liver cirrhosis and hepatocellular carcinoma, thus leading to liver
      related death. Currently, the optimal treatment for chronic hepatitis C infection
      is the combination of pegylated interferon and ribavirin. The aim of this review
      is to assess the long-term clinical outcomes of interferons alone or in
      combination with ribavirin in the management of chronic hepatitis C.

PMID- 22646259
TI  - Intestinal microbiota, pathophysiology and translation to probiotic use in
      patients with irritable bowel syndrome.
AB  - Probiotic agents have received growing attention in recent years as an
      alternative therapeutic tool in the management of irritable bowel syndrome. In
      this article, we will discuss the rationale that support this indication,
      including the role of intestinal microbiota in gastrointestinal function in both
      human and animal models, potential links between an impaired microbiota imbalance
      and the psycho-immunopathophysiology of irritable bowel syndrome, and the results
      of the available clinical trials to date.

PMID- 22646261
TI  - Chymase inhibition as a pharmacological target: a role in inflammatory and
      functional gastrointestinal disorders?
AB  - Chymase has been extensively studied with respect to its role in the
      pathophysiology of cardiovascular disease, and is notable for its role in the
      generation of angiotensin II, a mediator crucial in vascular remodelling.
      However, in more recent years, an association between chymase and several
      inflammatory diseases, including gastrointestinal (GI) disorders such as
      inflammatory bowel diseases (IBD) have been described. Such studies, to date,
      with respect to IBD at least, are descriptive in the clinical context;
      nonetheless, preclinical studies implicate chymase in the pathogenesis of gut
      inflammation. However, studies to elucidate the role of chymase in functional
      bowel disease are in their infancy, but suggest a plausible role for chymase in
      contributing to some of the phenotypic changes observed in such disorders, namely
      increased epithelial permeability. In this short review, we have summarized the
      current knowledge on the pathophysiological role of chymase and its inhibition
      with reference to inflammation and tissue injury outside of the GI tract and
      discussed its potential role in GI disorders. We speculate that chymase may be a
      novel therapeutic target in the GI tract, and as such, inhibitors of chymase
      warrant preclinical investigation in GI diseases.

PMID- 22646262
TI  - Questions on the significance of "indefinite for dysplasia" in Barrett
      metaplasia.

PMID- 22646264
TI  - Personalized medicine? Who has the tissue?

PMID- 22646265
TI  - Reevaluation and identification of the best immunohistochemical panel (pVHL,
      Maspin, S100P, IMP-3) for ductal adenocarcinoma of the pancreas.
AB  - CONTEXT: Differentiation of ductal adenocarcinoma of the pancreas from
      nonneoplastic pancreatic tissues can be challenging, especially in small biopsy
      and fine-needle aspiration specimens. OBJECTIVE: To investigate the utility of 26
      immunohistochemical markers (CAM 5.2, CK [cytokeratin] 7, CK20, CK17, CK19, MUC1,
      MUC2, MUC4, MUC5AC, MUC6, p53, DPC4/SMAD4, CDX2, pVHL [von Hippel-Lindau tumor
      suppressor gene protein], S100P, IMP-3 [insulin-like growth factor 2 messenger
      RNA binding protein 3], maspin, mesothelin, claudin 4, claudin 18, annexin A8,
      fascin, PSCA [prostate stem cell antigen], MOC31, CEA [carcinoembryonic antigen],
      and CA19-9 [cancer antigen 19-9]) in the diagnosis of ductal adenocarcinoma of
      the pancreas. DESIGN: Immunohistochemical staining for these markers was
      performed in 60 cases of pancreatic ductal adenocarcinoma on routine and tissue
      microarray sections. In addition, immunohistochemical staining for maspin, S100P,
      IMP-3, and pVHL was performed on cell blocks from 67 pancreatic fine-needle
      aspiration cases, including 44 cases of pancreatic ductal adenocarcinoma.
      RESULTS: The results demonstrated that (1) more than 90% of cases of ductal
      adenocarcinoma were positive for maspin, S100P, and IMP-3; (2) nearly all
      adenocarcinoma cases were negative for pVHL, whereas nonneoplastic ducts and
      acini were positive for pVHL in all cases; (3) normal/reactive pancreatic ducts
      were frequently positive for CK7, CK19, MUC1, MUC6, CA19-9, MOC31, PSCA,
      mesothelin, annexin A8, claudin 4, and claudin 18; (4) normal pancreatic ducts
      were usually negative for IMP-3, maspin, S100P, CK17, MUC2, MUC4, and MUC5AC; (5)
      60% of adenocarcinomas were negative for DPC4/SMAD4; and (6) strong background
      staining was frequently seen with fascin, PSCA, and annexin A8. CONCLUSIONS:
      pVHL, maspin, S100P, and IMP-3 constitute the best diagnostic panel of
      immunomarkers for confirming the diagnosis of pancreatic ductal adenocarcinoma in
      both surgical and fine-needle aspiration specimens.

PMID- 22646266
TI  - Quantitation of HER2/neu expression in primary gastroesophageal adenocarcinomas
      using conventional light microscopy and quantitative image analysis.
AB  - CONTEXT: Human epidermal growth factor receptor 2 (HER2/neu) is overexpressed in
      a proportion of gastroesophageal (GE) adenocarcinomas, and trastuzumab treatment
      results in significant improvement in overall survival in patients with HER2/neu
      overexpressing GE tumors. Grading of HER2/neu expression in GE tumors and its
      clinical application is different from that of breast cancer. HER2/neu
      immunohistochemistry (IHC) image analysis (IA), widely used in breast cancer, has
      not been studied in GE tumors. OBJECTIVE: To evaluate the correlation between
      manual HER2/neu IHC scoring and HER2/neu IHC image analysis in GE adenocarcinomas
      with characterization of associated clinicopathologic features. DESIGN: Tumor
      grade, growth pattern, and stage were evaluated in 116 cases of primary GE
      adenocarcinoma biopsy and resection specimens. Using anti-HER2/neu antibody and
      the proposed HER2/neu scoring system for gastric cancer, HER2/neu IHC expression
      was recorded after manual scoring and automated IA interpretation. RESULTS:
      HER2/neu overexpression (IHC 3+) was detected in 19% (10 of 54) of gastric
      tumors, and overall correlation between manual HER2/neu IHC interpretation and IA
      interpretation was 78% (42 of 54). HER2/neu overexpression (IHC 3+) was detected
      in 26% (16 of 62) of GE junction tumors, and the overall correlation between
      manual HER2/neu IHC interpretation and IA interpretation was 84% (52 of 62).
      CONCLUSIONS: The HER2/neu IHC scoring system for GE adenocarcinomas differs from
      that of breast carcinoma. Automated IA, validated for scoring of HER2/neu IHC in
      breast cancer, has a low correlation between HER2/neu IHC 2+ and IHC 3+ cases
      scored by conventional light microscopy and cannot be reliably used in the
      interpretation of HER2/neu IHC expression in GE adenocarcinomas.

PMID- 22646267
TI  - A histopathologic pattern of centrilobular hepatocyte injury suggests 6
      mercaptopurine-induced hepatotoxicity in patients with inflammatory bowel
      disease.
AB  - CONTEXT: Hepatotoxicity is an important side effect of thiopurine analog
      treatment for inflammatory bowel disease. A variety of histopathologic findings
      have been observed in patients with inflammatory bowel disease with thiopurine
      induced hepatotoxicity, including nodular regenerative hyperplasia, vascular
      injury, and cholestasis. OBJECTIVE: To describe the histologic features shared by
      3 cases of thiopurine-induced hepatotoxicity in patients with inflammatory bowel
      disease. DESIGN: We identified 3 patients with inflammatory bowel disease who
      developed hepatotoxicity due to 6-mercaptopurine from the educational files of
      the Department of Pathology at Massachusetts General Hospital (Boston). Histology
      slides (stained with hematoxylin-eosin, trichrome, periodic-acid Schiff with
      diastase digestion, and iron stains) and patients' medical records were reviewed
      retrospectively. RESULTS: All 3 patients were receiving 6-mercaptopurine
      monotherapy at therapeutic doses, had normal thiopurine metabolite levels, and
      presented with elevated aminotransferase levels. Biopsies from all 3 cases
      exhibited a pattern of centrilobular hepatocyte injury characterized by ceroid
      laden macrophages, hepatocyte anisonucleosis, and increased lipofuscin pigment,
      as well as centrilobular steatosis. Aminotransferase levels trended downward and
      either normalized or remained at borderline elevated levels after 6
      mercaptopurine dose was reduced (in 1 patient) or discontinued (in 2 patients).
      CONCLUSIONS: Recognition of a pattern of centrilobular injury enables
      pathologists to suggest thiopurine-induced liver injury as the cause of elevated
      aminotransferases in patients with inflammatory bowel disease.

PMID- 22646268
TI  - ALK-1 protein expression and ALK gene rearrangements aid in the diagnosis of
      inflammatory myofibroblastic tumors of the female genital tract.
AB  - CONTEXT: Inflammatory myofibroblastic tumor is a predominantly benign, spindle
      cell, mesenchymal neoplasm with myxoid areas that occurs rarely in the female
      genital tract and may be confused with other spindle cell lesions, particularly
      leiomyosarcoma. OBJECTIVE: To investigate the utility of detecting anaplastic
      lymphoma kinase-1 protein expression and ALK gene rearrangements in the diagnosis
      of inflammatory myofibroblastic tumors in the female genital tract. DESIGN: Eight
      inflammatory myofibroblastic tumors arising in the female genital tract and seen
      in consultation (from 2004 to 2011) were reviewed. Immunohistochemistry for
      anaplastic lymphoma kinase-1 and fluorescence in-situ hybridization studies for
      ALK gene rearrangements were performed. RESULTS: The anatomic sites included
      myometrium (4 cases) and endometrium, fallopian tube, cervix, and a cervical
      polyp (1 each), with a patient age range from 25 to 52 years. Histologic features
      ranged from bland spindle cells to striking cytologic atypia, embedded in a
      prominent myxoid background. Anaplastic lymphoma kinase-1 immunohistochemistry
      was positive in 7 cases. Fluorescence in-situ hybridization studies detected ALK
      gene rearrangements in 5 cases. Five cases had both immunopositivity and
      fluorescence in-situ hybridization abnormalities, 2 cases had immunopositivity
      only, and 1 case was negative by both methods. CONCLUSIONS: This is the first
      report, to our knowledge, of ALK gene rearrangements in inflammatory
      myofibroblastic tumors in the female genital tract. If a myxoid background is
      appreciated in a spindle cell lesion of the female genital tract, especially if
      inflammatory cells are present, anaplastic lymphoma kinase-1 staining along with
      fluorescence in situ hybridization studies, for ALK gene rearrangements, may aid
      in distinguishing inflammatory myofibroblastic tumors from their malignant
      mimics.

PMID- 22646269
TI  - Automated quantification of MART1-verified Ki67 indices by digital image analysis
      in melanocytic lesions.
AB  - CONTEXT: The proliferation marker Ki67 is an important diagnostic and prognostic
      aid in surgical pathology. However, manual quantification in a counting frame to
      accurately establish the proliferation rate (Ki67 index) is cumbersome and time
      consuming. Instead, digital image analysis of Ki67/MART1 double stains may
      provide fast and novel index computations for entire tumor sections. OBJECTIVES:
      To design and compare image analysis protocols that compute Ki67 indices of
      Ki67/MART1 double stains, to compare automated indices with previously published
      manual indices, and to compare the total number of proliferating cells (mimicking
      a Ki67 single stain) with the number of MART1-verified proliferating cells.
      DESIGN: Whole slide images were captured from 48 melanomas and 77 nevi stained
      with an immunohistochemical cocktail against Ki67 and MART1. Ki67 indices were
      determined by digital image analysis and different equations based on number or
      area. RESULTS: The differences between mean indices of melanomas and nevi were
      significant (P < .001) in all index computations. Number-based image analysis of
      lesions with more than 250 melanocytic cells misclassified 1 of 42 melanomas and
      4 of 53 nevi, numbers comparable with manual counting. Automated indices were
      significantly higher than manual indices, as were indices of mimicked Ki67 single
      stains compared with MART1-verified Ki67 indices (P < .001). CONCLUSIONS: Ki67
      indices established by digital image analysis of Ki67/MART1 double stains
      demonstrated excellent abilities to discriminate melanomas from nevi with
      diagnostic performances equal to manually performed indices. Testing different
      definitions of the automated MART1-verified Ki67 index, no single definition
      stood out; thus, a variety of definitions may be used.

PMID- 22646270
TI  - Lymphovascular invasion in micropapillary urothelial carcinoma: a study of 22
      cases.
AB  - CONTEXT: Micropapillary urothelial carcinoma (MPUC) is a known aggressive variant
      of urothelial carcinoma. However, the reasons for its aggressiveness remain
      unclear. OBJECTIVE: To investigate the frequency of lymphovascular invasion in 22
      cases of MPUC. DESIGN: Consecutive tissue sections were stained with D2-40 and
      CD34 to highlight lymphovascular channels associated with MPUC. Spaces containing
      tumor cells were scored as positive for lymphovascular invasion if the staining
      pattern on immunohistochemistry was distinct and circumferential. RESULTS: Of 22
      cases, 21 (95%) had lymphovascular invasion on immunohistochemical staining, with
      91% lymphatic invasion and 4% vascular invasion. Interestingly, 8 cases were
      originally signed out as negative for lymphovascular invasion on the basis of
      hematoxylin-eosin-stained sections; of these, 7 (88%) had focal lymphovascular
      invasion evident on immunohistochemical staining. CONCLUSIONS: Our results
      confirm that micropapillary lacunae are not lymphovascular channels. However,
      nearly all MPUC tumors (95% in this series) have evidence of lymphovascular
      invasion by immunohistochemical analysis. Our data support the use of
      micropapillary features as a morphologic marker for lymphovascular invasion and
      MPUC as an adverse histologic type of urothelial carcinoma.

PMID- 22646271
TI  - Endovascular infections caused by Histoplasma capsulatum: a case series and
      review of the literature.
AB  - CONTEXT: Endovascular infection is an uncommon but devastating manifestation of
      histoplasmosis, which is often diagnosed late in disease. OBJECTIVES: To evaluate
      the clinical and pathologic characteristics of patients with endovascular
      infections caused by Histoplasma capsulatum. DESIGN: All cases of patients with
      documented endovascular histoplasmosis at a single tertiary care center in an
      endemic region during the period 1993-2010 were reviewed. RESULTS: Patients
      presented with a subacute febrile illness and a history of endovascular devices.
      All patients had positive Histoplasma serology. Routine bacterial culture results
      were negative for all patients. In addition to yeast forms typical of
      histoplasmosis, pathologic findings also revealed mycelial forms in 4 of 5
      patients. Inflammation was scant. Urinary antigen detection was positive in 4 of
      5 patients and Histoplasma blood culture results were positive for 3 of 5
      patients. Four patients were treated with a combination of surgical and medical
      therapy, which consisted of amphotericin B followed by itraconazole; these 4
      patients had complete resolution of symptoms and no documented relapse. One
      patient died before planned surgery. CONCLUSIONS: Histoplasma capsulatum
      endovascular infections are clinically characterized by a subacute febrile
      illness with negative bacterial cultures in patients with prosthetic endografts
      or valves. Noninvasive diagnostics are often the initial clue to the diagnosis.
      Combined medical and surgical treatment is associated with survival. On
      histopathologic examination both mycelial and yeast forms are often observed,
      with absent to minimal tissue inflammatory reaction.

PMID- 22646272
TI  - NLRP7 mutation analysis in sporadic hydatidiform moles in Tunisian patients:
      NLRP7 and sporadic mole.
AB  - CONTEXT: Hydatidiform mole, an aberrant human pregnancy, is commonly a
      nonrecurrent disease. Recently, a rare autosomal recessive form of familial
      and/or recurrent molar pregnancies was associated with mutations in the NLRP7
      gene. OBJECTIVE: To investigate whether NLRP7 mutations exist in Tunisian women
      with sporadic hydatidiform moles. DESIGN: Genomic DNA from 38 unrelated Tunisian
      patients with sporadic hydatidiform moles were screened by sequencing all NLRP7
      exons. A high-resolution melting curve analysis was performed on 170 DNA controls
      to analyze new sequence variants. RESULTS: More than 13% of these patients were
      heterozygous for NLRP7 mutations. We found 2 novel missense mutations in the
      heterozygous state, c.544G>A (p.Val182Met) in 1 patient and c.1480G>A
      (p.Ala494Thr) in 2 patients, and 2 already reported mutations, c.1532A>G
      (p.Lys511Arg) and c.2156C>T (p.Ala719Val), in 2 patients. None of these mutations
      were identified in 170 controls except for 1 woman who was heterozygous for
      p.Val182Met. CONCLUSION: As homozygous NLRP7 mutations are associated with
      recurrent hydatidiform mole or conception loss, the heterozygous state could
      represent a risk factor for nonrecurrent mole.

PMID- 22646273
TI  - Structured electronic template for histopathology reporting on colorectal
      carcinoma resections: five-year follow-up shows sustainable long-term quality
      improvement.
AB  - CONTEXT: To improve quality, pathology organizations have published guidelines
      with key parameters for histopathology reporting on cancer resections. Checklists
      or structured templates improve upon the presence of key parameters in
      histopathology reports, but data are lacking on long-term sustainability of such
      reporting. From 2003 to 2006, the Cancer Registry of Norway and the Norwegian
      Society of Pathology collaborated on the development of a structured electronic
      template for histopathology reporting on colorectal carcinoma resections.
      OBJECTIVE: To investigate use and long-term effect of this structured template in
      one of the first laboratories implementing the template for routine diagnostic
      work. DESIGN: All histopathology reports (n =123) in the 1-year period prior to
      implementation were evaluated with respect to presence of key parameters.
      Likewise, all histopathology reports (n =1186) in the 5-year period after
      implementation were evaluated with respect to template use and presence of key
      parameters. RESULTS: The electronic template had been used in 1089 (91.8%) of the
      1186 cases. Template use was stable in the entire 5-year period, and had
      significantly improved upon the presence of data on 7 of 11 key parameters valid
      for both the pre-implementation and the post-implementation period. Eight hundred
      and twenty-two (75.5%) of the 1089 template reports contained information on all
      key parameters, compared to just 20 (16.3%) of the 123 free text reports in the 1
      year pre-implementation period. CONCLUSION: Electronic template reporting has a
      significant and sustainable long-term, positive effect upon the quality of
      histopathology reports.

PMID- 22646274
TI  - CD68 immunostaining in the evaluation of chronic histiocytic intervillositis.
AB  - CONTEXT: Chronic histiocytic intervillositis is an uncommon and poorly recognized
      lesion associated with poor perinatal outcomes, including intrauterine growth
      retardation and stillbirth. It has a high recurrence rate. OBJECTIVE: To evaluate
      utility of CD68 immunostaining in the evaluation of chronic histiocytic
      intervillositis. DESIGN: Institutional review board-approved retrospective review
      was performed. Cases were selected from the departmental archives of University
      Hospital, Newark, New Jersey, between 2002 and 2009. Controls were from second
      trimester pregnancies with chromosomal abnormalities or multiple severe
      anomalies. RESULTS: There were 9 cases and 11 controls. The mean CD68(+) count
      per high-power field for the cases was 88 +/- 23 (range, 51-180) and for the
      controls, 8 +/- 5 (range, 0-24), P < .001. CONCLUSIONS: This study establishes a
      range for histiocyte counts in chronic histiocytic intervillositis and
      pregnancies without chronic histiocytic intervillositis, and suggests that CD68
      staining may have utility in the diagnosis, particularly for nonperinatal
      pathologists, who may be less familiar with this lesion.

PMID- 22646275
TI  - Evaluation of an automated digital imaging system, Nextslide Digital Review
      Network, for examination of peripheral blood smears.
AB  - CONTEXT: Several automated digital imaging systems have been introduced in recent
      years to improve turnaround time and proficiency in examining peripheral blood
      smears in hematology laboratories. OBJECTIVE: To evaluate a new automated digital
      imaging system, Nextslide Digital Review Network (Nextslide), for examination of
      peripheral blood smears. DESIGN: We evaluated 479 peripheral blood smears, of
      which 247 (51.6%) were included for comparison of Nextslide and manual white
      blood cell differential counts and morphology evaluation, 204 (42.6%) were
      included for comparison of Nextslide and CellaVision (DM96) differential counts,
      and 28 (5.8%) were neonatal samples examined for enumeration of nucleated red
      blood cells. RESULTS: Results from both method comparisons showed excellent
      correlation for all major white blood cell classes with correlation coefficients
      ranging from 0.70 to 0.99. Evaluation of white blood cell, red blood cell, and
      platelet morphology also showed good correlation among methods. White blood cell
      preclassification capability in the system was evaluated for rate and accuracy.
      Leukopenic samples demonstrated markedly decreased review time with Nextslide.
      Enumeration of nucleated red blood cells showed good correlation among methods.
      CONCLUSIONS: Our evaluation of Nextslide shows excellent correlation when
      compared with conventional manual differentials and CellaVision (DM96)
      differentials for evaluation of peripheral blood smears.

PMID- 22646276
TI  - Biospecimens and biorepositories for the community pathologist.
AB  - Pathologists have long served as custodians of human biospecimens collected for
      diagnostic purposes. Rapid advancements in diagnostic technologies require that
      pathologists change their practices to optimize patient care. The proper handling
      of biospecimens creates opportunities for pathologists to improve their diagnoses
      while assessing prognosis and treatment. In addition, the growing need for high
      quality biorepositories represents an opportunity for community pathologists to
      strengthen their role within the health care team, ensuring that clinical care is
      not compromised while facilitating research. This article provides a resource to
      community pathologists learning how to create high-quality biorepositories and
      participating in emerging opportunities in the biorepository field. While a
      variety of topics are covered to provide breadth of information, the intent is to
      facilitate a level of understanding that permits community pathologists to make
      more informed choices in identifying how best their skills and practice may be
      augmented to address developments in this field.

PMID- 22646277
TI  - Necrotizing palisading granuloma of the bladder in an otherwise healthy young
      man.
AB  - We describe a case of a vesical mass in a young patient, histologically
      characterized by an intramural lesion composed of spindle and epithelioid
      histiocytes arranged in a palisaded pattern, with central necrosis similar to a
      rheumatoid nodule. There was no clinical history of autoimmunity or previous
      bladder procedures, infections, or trauma. However, the smooth muscle actin and
      desmin positivities seen in residual ghost cells within necrotic areas argued
      against a granulomatous process. Reactive processes, such as myofibroblastic
      proliferations, can overlap neoplastic disorders, including true smooth muscle
      tumors. We did not observe atypia in the viable cells and mitotic figures. These
      features did not support a diagnosis of malignancy. The fascicular pattern,
      spindle cell morphology, lack of marked cytologic atypia, and smooth muscle actin
      and desmin reactivities, with a lack of other lineage marker expression, all
      supported a diagnosis of an infarcted leiomyoma. The intramural location in the
      bladder also favored the diagnosis.

PMID- 22646278
TI  - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive
      to steroids following influenza vaccination.
AB  - Inflammatory processes within the central nervous system are challenging for the
      clinician, radiologist, and pathologist alike. They often can mimic other more
      well-known and defined disease processes. We present the case of a patient with a
      newly described inflammatory process that primarily involves the pons and
      adjacent structures, which is called chronic lymphocytic inflammation with
      pontine perivascular enhancement responsive to steroids (CLIPPERS). An 80-year
      old man presented with numbness of his right hand that ultimately progressed to
      involve both lower extremities and face and was associated with mild dysarthria
      and ataxia. He had received the influenza vaccination 2 weeks prior. The biopsy
      revealed primarily reactive T-cell lymphocytic infiltrates with macrophages and
      gliosis. Treatment required long-term immunosuppressive therapy. CLIPPERS is a
      recently described central nervous system inflammatory condition that should be
      considered in the differential diagnosis when a prominent lymphocytic
      inflammatory infiltrate is encountered in brainstem, spinal cord, midbrain, or
      cerebellar biopsies.

PMID- 22646279
TI  - Renal primitive neuroectodermal tumors.
AB  - Primitive neuroectodermal tumors exist as a part of the Ewing sarcoma/primitive
      neuroectodermal tumor family. These tumors most commonly arise in the chest wall
      and paraspinal regions; cases with a renal origin are rare entities, but have
      become increasingly reported in recent years. Although such cases occur across a
      wide age distribution, the average age for a patient with a renal primitive
      neuroectodermal tumor is the mid- to late 20s, with both males and females
      susceptible. Histologically, these tumors are characterized by pseudorosettes.
      Immunohistochemically, CD99 is an important diagnostic marker. Clinically, these
      are aggressive tumors, with an average 5-year disease-free survival rate of only
      45% to 55%. Given that renal primitive neuroectodermal tumor bears many
      similarities to other renal tumors, it is important to review the histologic
      features, immunostaining profile, and genetic abnormalities that can be used for
      its correct diagnosis.

PMID- 22646280
TI  - HER2/neu gene amplification and protein overexpression in gastric and
      gastroesophageal junction adenocarcinoma: a review of histopathology, diagnostic
      testing, and clinical implications.
AB  - Amplification of the human epidermal growth factor receptor 2/neu (HER2/neu) gene
      and overexpression of the HER2 protein (HER2) have been shown to occur in gastric
      and gastroesophageal junction adenocarcinoma in a number of studies. With a
      dismal survival rate, patients with these cancers stand to benefit from the
      identification of possible molecular targets such as HER2 for both prognostic and
      therapeutic purposes. Although these and other carcinomas that overexpress HER2
      may have a poorer prognosis and exhibit resistance to conventional chemotherapy,
      they have also recently been shown to respond to targeted therapy with the anti
      HER2 antibody trastuzumab. Here, we briefly review the molecular biology,
      histopathology, diagnostic techniques, and interpretation, as well as the
      clinical implications, of HER2 amplification/overexpression in gastric and
      gastroesophageal adenocarcinoma.

PMID- 22646281
TI  - Reliability of genetic bottleneck tests for detecting recent population declines.
AB  - The identification of population bottlenecks is critical in conservation because
      populations that have experienced significant reductions in abundance are subject
      to a variety of genetic and demographic processes that can hasten extinction.
      Genetic bottleneck tests constitute an appealing and popular approach for
      determining if a population decline has occurred because they only require
      sampling at a single point in time, yet reflect demographic history over multiple
      generations. However, a review of the published literature indicates that, as
      typically applied, microsatellite-based bottleneck tests often do not detect
      bottlenecks in vertebrate populations known to have experienced declines. This
      observation was supported by simulations that revealed that bottleneck tests can
      have limited statistical power to detect bottlenecks largely as a result of
      limited sample sizes typically used in published studies. Moreover, commonly
      assumed values for mutation model parameters do not appear to encompass variation
      in microsatellite evolution observed in vertebrates and, on average, the
      proportion of multi-step mutations is underestimated by a factor of approximately
      two. As a result, bottleneck tests can have a higher probability of 'detecting'
      bottlenecks in stable populations than expected based on the nominal significance
      level. We provide recommendations that could add rigor to inferences drawn from
      future bottleneck tests and highlight new directions for the characterization of
      demographic history.

PMID- 22646282
TI  - [2,3]-Sigmatropic rearrangement of ynamides: preparation of alpha-amino
      allenephosphonates.
AB  - alpha-Amino allenephosphonates were easily prepared in two steps from protected
      amines, propargyl alcohols, and chlorophosphites. First, ynamides were
      synthesized from unprotected 1-bromopropargyl alcohols using a copper(II)
      catalyzed coupling reaction. In the second step, the previously prepared ynamides
      were transformed directly to allenes through a [2,3]-sigmatropic rearrangement of
      propargyl phosphites. This efficient method led to the formation of a series of
      alpha-amino allenephosphonates with diverse substituents on the amine, the
      phosphonate, and the allene moieties.

PMID- 22646283
TI  - Multivalent ligand displayed on plant virus induces rapid onset of bone
      differentiation.
AB  - Viruses are monodispersed biomacromolecules with well-defined 3-D structures at
      the nanometer level. The relative ease to manipulate viral coat protein gene to
      display numerous functional groups affords an attractive feature for these
      nanomaterials, and the inability of plant viruses to infect mammalian hosts poses
      little or no cytotoxic concerns. As such, these nanosized molecular tools serve
      as powerful templates for many pharmacological applications ranging as
      multifunctional theranostic agents with tissue targeting motifs and imaging
      agents, potent vaccine scaffolds to induce cellular immunity and for probing
      cellular functions as synthetic biomaterials. The results herein show that
      combination of serum-free, chemically defined media with genetically modified
      plant virus induces rapid onset of key bone differentiation markers for bone
      marrow derived mesenchymal stem cells within two days. The xeno-free culture is
      often a key step toward development of ex vivo implants, and the early onset of
      osteocalcin, BMP-2 and calcium sequestration are some of the key molecular
      markers in the progression toward bone formation. The results herein will provide
      some key insights to engineering functional materials for rapid bone repair. 

PMID- 22646284
TI  - Detection of MAGE-A expression predicts malignant transformation of oral
      leukoplakia.
AB  - The study aimed at checking if MAGE-A expression in oral leukoplakia (OLP)
      lesions is related to malignant transformation. The 48 samples of OLP that
      transformed to oral squamous cell carcinoma (OSCC) (group 1) and 50 samples of
      OLP that did not transform to OSCC (group 2) were included in the study. The
      expression of MAGE-A was restricted to group 1. The correlation between malignant
      transformation and MAGE-A occurrence in OLP was statistically significant (p <
      .0001). Detection of MAGE-A may allow identifying OLP with a high risk of
      malignant transformation giving a view to a new approach to prevention of oral
      cancer.

PMID- 22646285
TI  - The influence of piezoelectric scaffolds on neural differentiation of human
      neural stem/progenitor cells.
AB  - Human neural stem/progenitor cells (hNSCs/NPCs) are a promising cell source for
      neural tissue engineering because of their ability to differentiate into various
      neural lineages. In this study, hNSC/NPC differentiation was evaluated on
      piezoelectric, fibrous scaffolds. These smart materials have an intrinsic
      material property where transient electric potential can be generated in the
      material upon minute mechanical deformation. hNSCs/NPCs cultured on the scaffolds
      and films differentiated into beta-III tubulin-positive cells, a neuronal cell
      marker, with or without the presence of inductive factors. In contrast,
      hNSCs/NPCs cultured on laminin-coated plates were predominantly nestin positive,
      a NSC marker, in the control medium. Gene expression results suggest that the
      scaffolds may have promoted the formation of mature neural cells exhibiting
      neuron-like characteristics. hNSCs/NPCs differentiated mostly into beta-III
      tubulin-positive cells and had the greatest average neurite length on micron
      sized, annealed (more piezoelectric), aligned scaffolds, demonstrating their
      potential for neural tissue-engineering applications.

PMID- 22646286
TI  - Sesamin stimulates osteoblast differentiation through p38 and ERK1/2 MAPK
      signaling pathways.
AB  - BACKGROUND: Osteoporosis is a worldwide health problem predominantly affecting
      post-menopausal women. Therapies aimed at increasing bone mass in osteoporetic
      patients lag behind comparable investigation of therapeutic strategies focusing
      on the bone resorption process. Sesamin, a major lignan compound found in Sesamun
      indicum Linn., has a variety of pharmacological effects, though its activity on
      bone cell function is unclear. Herein we examine the effect of this lignan on
      osteoblast differentiation and function. METHOD: Cell cytotoxicity and
      proliferative in hFOB1.19 were examined by MTT and alamar blue assay up to 96 h
      of treatment. Gene expression of COL1, ALP, BMP-2, Runx2, OC, RANKL and OPG were
      detected after 24 h of sesamin treatment. ALP activity was measured at day 7, 14
      and 21 of cultured. For mineralized assay, ADSCs were cultured in the presence of
      osteogenic media supplement with or without sesamin for 21 days and then stained
      with Alizarin Red S. MAPK signaling pathway activation was observed by using
      western blotting. RESULTS: Sesamin promoted the gene expression of COL1, ALP,
      OCN, BMP-2 and Runx2 in hFOB1.19. On the other hand, sesamin was able to up
      regulate OPG and down-regulate RANKL gene expression. ALP activity also
      significantly increased after sesamin treatment. Interestingly, sesamin induced
      formation of mineralized nodules in adipose derived stem cells (ADSCs) as
      observed by Alizarin Red S staining; this implies that sesamin has anabolic
      effects both on progenitor and committed cell stages of osteoblasts. Western
      blotting data showed that sesamin activated phosphorylation of p38 and ERK1/2 in
      hFOB1.19. CONCLUSIONS: The data suggest that sesamin has the ability to trigger
      osteoblast differentiation by activation of the p38 and ERK MAPK signaling
      pathway and possibly indirectly regulate osteoclast development via the
      expression of OPG and RANKL in osteoblasts. Therefore, sesamin may be a promising
      phytochemical that could be developed for supplementation of osteoporotic
      therapy.

PMID- 22646288
TI  - Membrane traffic and synaptic cross-talk during host cell entry by Trypanosoma
      cruzi.
AB  - It is widely accepted that Trypanosoma cruzi can exploit the natural exocytic
      response of the host to cell damage, utilizing host cell lysosomes as important
      effectors. It is, though, increasingly clear that the parasite also exploits
      endocytic mechanisms which allow for incorporation of plasma membrane into the
      parasitophorous vacuole. Further, that these endocytic mechanisms are involved in
      cross-talk with the exocytic machinery, in the recycling of vesicles and in the
      manipulation of the cytoskeleton. Here we review the mechanisms by which T. cruzi
      exploits features of the exocytic and endocytic pathways in epithelial and
      endothelial cells and the evidence for cross-talk between these pathways.

PMID- 22646287
TI  - One misdated sequence of rabbit hemorrhagic disease virus prevents accurate
      estimation of its nucleotide substitution rate.
AB  - BACKGROUND: The literature is ripe with phylogenetic estimates of nucleotide
      substitution rates, especially of measurably evolving species such as RNA
      viruses. However, it is not known how robust these rate estimates are to
      inaccuracies in the data, particularly in sampling dates that are used for
      molecular clock calibration. Here we report on the rate of evolution of the
      emerging pathogen Rabbit hemorrhagic disease virus (RHDV), which has
      significantly different rates of evolution for the same outer capsid (VP60) gene
      published in the literature. In an attempt to reconcile the conflicting data and
      further elucidate details of RHDV 's evolutionary history, we undertook fresh
      Bayesian analyses and employed jackknife control methods to produce robust
      substitution rate and time to most recent common ancestor (TMRCA) estimates for
      RHDV based on the VP60 and RNA-dependent RNA polymerase genes. RESULTS: Through
      these control methods, we were able to identify a single misdated taxon, a
      passaged lab strain used for vaccine production, which was responsible for
      depressing the RHDV capsid gene's rate of evolution by 65%. Without this isolate,
      the polymerase and the capsid protein genes had nearly identical rates of
      evolution: 1.90x10-3 nucleotide substitutions/site/year, ns/s/y, (95% highest
      probability density (HPD) 1.25x10-3-2.55x10-3) and 1.91x10-3 ns/s/y (95% HPD
      1.50x10-3-2.34x10-3), respectively. CONCLUSIONS: After excluding the misdated
      taxon, both genes support a significantly higher substitution rate as well as a
      relatively recent emergence of RHDV, and obviate the need for previously
      hypothesized decades of unobserved diversification of the virus. The control
      methods show that using even one misdated taxon in a large dataset can
      significantly skew estimates of evolutionary parameters and suggest that it is
      better practice to use smaller datasets composed of taxa with unequivocal
      isolation dates. These jackknife controls would be useful for future tip
      calibrated rate analyses that include taxa with ambiguous dates of isolation.

PMID- 22646289
TI  - Coffee and caffeine protect against liver injury induced by thioacetamide in male
      Wistar rats.
AB  - Coffee intake has been inversely related to the incidence of liver diseases,
      although there are controversies on whether these beneficial effects on human
      health are because of caffeine or other specific components in this popular
      beverage. Thus, this study evaluated the protective effects of coffee or caffeine
      intake on liver injury induced by repeated thioacetamide (TAA) administration in
      male Wistar rats. Rats were randomized into five groups: one untreated group (G1)
      and four groups (G2-G5) treated with the hepatotoxicant TAA (200 mg/kg b.w.,
      i.p.) twice a week for 8 weeks. Concomitantly, rats received tap water (G1 and
      G2), conventional coffee (G3), decaffeinated coffee (G4) or 0.1% caffeine (G5).
      After 8 weeks of treatment, rats were killed and blood and liver samples were
      collected. Conventional and decaffeinated coffee and caffeine intake
      significantly reduced serum levels of alanine aminotransferase (ALT) (p < 0.001)
      and oxidized glutathione (p < 0.05), fibrosis/inflammation scores (p < 0.001),
      collagen volume fraction (p < 0.01) and transforming growth factor beta-1 (TGF
      beta1) protein expression (p <= 0.001) in the liver from TAA-treated groups. In
      addition, conventional coffee and caffeine intake significantly reduced
      proliferating cellular nuclear antigen (PCNA) S-phase indexes (p < 0.001), but
      only conventional coffee reduced cleaved caspase-3 indexes (p < 0.001), active
      metalloproteinase 2 (p <= 0.004) and the number of glutathione S-transferase
      placental form (GST-P)-positive preneoplastic lesions (p < 0.05) in the liver
      from TAA-treated groups. In conclusion, conventional coffee and 0.1% caffeine
      intake presented better beneficial effects than decaffeinated coffee against
      liver injury induced by TAA in male Wistar rats.

PMID- 22646290
TI  - Heparin-induced acute adverse reaction--case report of a patient with acute
      trauma and a genetic predisposition to thrombotic events: a concurrence of
      events.
AB  - WHAT IS KNOWN AND OBJECTIVE: The most common complication of heparin therapy is
      bleeding. Allergic reactions to heparin are rare, and the mechanisms are poorly
      understood. We report on a case of acute systemic reaction after subcutaneous
      injections of a low-molecular-weight heparin (LMWH) in a patient with a genetic
      predisposition to thrombotic events and review the literature on heparin-induced
      acute adverse reaction. CASE SUMMARY: A 57-year-old diabetic,
      hypertriglyceridemic and hypercholesterolemic man was admitted with a fractured
      right malleolus sustained while driving. He was prescribed parnaparin sodium 4250
      IU subcutaneously once a day. During the third injection, the patient developed
      widespread pain, sickness and facial rash, followed by a state of stupor (Glasgow
      Coma Scale 8) and was hospitalized in Neurological Unit. He was found to be a
      carrier of two genetic mutations (i.e. prothrombin G20210A and MTHFR mutation)
      associated with an increased risk of thrombotic events. Discontinuation of
      parnaparin and supportive care led to a sufficient recovery of the patient to be
      discharged 6 days after admission. WHAT IS NEW AND CONCLUSION: Treatment for
      heparin-related hypersensitivity reactions is largely supportive and symptomatic.
      Clinicians should be aware of these rare but potentially serious adverse events.
      Prothrombin gene mutations are quite common, and guidelines on anticoagulant
      therapy for affected patients are needed.

PMID- 22646291
TI  - Ferrocene-dithiolene hybrids: control of strong donor-acceptor electronic
      communication to reverse the charge transfer direction.
AB  - We prepared a novel class of ferrocene-dithiolene hybrid molecules, FcS4dt(Me)2
      and FcS4dt[Pt((t)Bu2bpy)] (where FcS4dt indicates 2-(1,3-dithia[3]ferrocenophane
      2-ylidene)-1,3-dithiole-4,5-dithiolate and (t)Bu2bpy indicates 4,4'-di-tert-butyl
      2,2'-bipyridine), in which the ferrocene moiety was bound to the planar
      conjugated dithiolene skeleton via two sulfur atoms such that the
      cyclopentadienyl rings were perpendicular to the dithiolene backbone. The
      physical properties and electronic structures of the complexes and their oxidized
      species [FcS4dt(Me)2](*+) and [FcS4dt[Pt((t)Bu2bpy)]](*+) were investigated by
      means of single-crystal X-ray diffraction (XRD) analysis, cyclic voltammetry,
      electron paramagnetic resonance (EPR), and UV-vis near infrared (UV-vis-NIR)
      spectroscopy. The electron density distributions of the highest occupied
      molecular orbitals (HOMOs) of FcS4dt(Me)2 and FcS4dt[Pt((t)Bu2bpy)] differed
      remarkably in that the HOMO of the former was ferrocene-based whereas that of the
      latter was dithiolene-based. The differences in the HOMO distributions originated
      from the energy level of the dithiolene-based pi-orbital in each of the
      complexes, which was controlled by changing R in FcS4dt(R)2 (R = Me for
      FcS4dt(Me)2; 2R = Pt((t)Bu2bpy) for FcS4dt[Pt((t)Bu2bpy)]). We succeeded in
      analyzing the crystal structure of [FcS4dt[Pt((t)Bu2bpy)]](F4TCNQ).C6H14.CH2Cl2
      (where F4TCNQ indicates 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane),
      which provided a rare example of the crystal structure of a
      [Pt(diimine)(dithiolate)](*+) ion-based complex. A comparison of the bond lengths
      in FcS4dt[Pt((t)Bu2bpy)] and [FcS4dt[Pt((t)Bu2bpy)]](*+) suggested that the
      latter complex displayed a conjugated dithiolene-based pi-radical character.
      These considerations agreed well with the electronic structures calculated using
      density functional theory (DFT) and time-dependent(TD)-DFT methods. Significant
      electronic communication between the ferrocene and dithiolene moieties was
      detected for both [FcS4dt(Me)2](*+) and [FcS4dt[Pt((t)Bu2bpy)]](*+) in the
      appearance of an intramolecular charge transfer band, which was hardly observed
      for previously reported ferrocene-dithiolene hybrid molecules. The charge
      transfer direction was reversed between the two cations. The electron coupling
      parameter HAB and the potential energy curves of the oxidized complexes were
      estimated based on the classical two-state Marcus-Hush theory. These results
      suggest that FcS4dt-based metalladithiolenes can exhibit controllable electronic
      structures expressed as double-minimum potential energy curves. 

PMID- 22646292
TI  - Ligand-dependent nucleo-cytoplasmic shuttling of peroxisome proliferator
      activated receptors,  PPARalpha  and  PPARgamma.
AB  - Peroxisome proliferator-activated receptors (PPARs) play important roles in
      diverse biological processes including metabolisms of sugars and lipids and
      differentiation of cells such as adipocytes. PPARs are transcription factors
      belonging to the ligand-dependent hormone receptor group. To function as
      transcription factors, PPARs translocate into nucleus where they associate with
      transcription apparatus. However, mechanisms underlying nuclear transport of
      PPARs remain enigmatic. We show here that PPARalpha and PPARgamma dynamically
      shuttle between nucleus and cytoplasm, although they constitutively and
      predominantly appear in nucleus. With a series of truncation mutants, we identify
      that PPAR nuclear transport is mediated by at least two nuclear localization
      signals (NLSs) in DNA-binding domain (DBD)-hinge and activation function 1 (AF1)
      regions and their respective receptors including importinalpha/beta, importin 7,
      and an unidentified receptor. PPARs also harbor two nuclear export signals in DBD
      and ligand-binding domain regions that are recognized by distinct export
      receptors, calreticulin and CRM1. Moreover, we show that nuclear-cytoplasmic
      shuttling of PPARs is regulated by respective PPAR ligands and Ca2+
      concentration. Taken together, we suggest that the multiple pathways for the
      nuclear-cytoplasmic transport of PPARs regulate the biological functions of PPARs
      in response to external signals.

PMID- 22646293
TI  - Neurologic disease attributed to a pituitary adenoma in an alpaca.

PMID- 22646294
TI  - Platelet lysate 3D scaffold supports mesenchymal stem cell chondrogenesis: an
      improved approach in cartilage tissue engineering.
AB  - Articular lesions are still a major challenge in orthopedics because of
      cartilage's poor healing properties. A major improvement in therapeutics was the
      development of autologous chondrocytes implantation (ACI), a biotechnology
      derived technique that delivers healthy autologous chondrocytes after in vitro
      expansion. To obtain cartilage-like tissue, 3D scaffolds are essential to
      maintain chondrocyte differentiated status. Currently, bioactive 3D scaffolds are
      promising as they can deliver growth factors, cytokines, and hormones to the
      cells, giving them a boost to attach, proliferate, induce protein synthesis, and
      differentiate. Using mesenchymal stem cells (MSCs) differentiated into
      chondrocytes, one can avoid cartilage harvesting. Thus, we investigated the
      potential use of a platelet-lysate-based 3D bioactive scaffold to support
      chondrogenic differentiation and maintenance of MSCs. The MSCs from adult rabbit
      bone marrow (n = 5) were cultivated and characterized using three antibodies by
      flow cytometry. MSCs (1 * 10(5)) were than encapsulated inside 60 ul of a rabbit
      platelet-lysate clot scaffold and maintained in Dulbecco's Modified Eagle Medium
      Nutrient Mixture F-12 supplemented with chondrogenic inductors. After 21 days,
      the MSCs-seeded scaffolds were processed for histological analysis and stained
      with toluidine blue. This scaffold was able to maintain round-shaped cells,
      typical chondrocyte metachromatic extracellular matrix deposition, and isogenous
      group formation. Cells accumulated inside lacunae and cytoplasm lipid droplets
      were other observed typical chondrocyte features. In conclusion, the usage of a
      platelet-lysate bioactive scaffold, associated with a suitable chondrogenic
      culture medium, supports MSCs chondrogenesis. As such, it offers an alternative
      tool for cartilage engineering research and ACI.

PMID- 22646295
TI  - Long-term adjuvant therapy for the prevention of postoperative endometrioma
      recurrence: a systematic review and meta-analysis.
AB  - Ovulation seems crucial in the pathogenesis of ovarian endometriomas. Therefore,
      suppression of ovulation should be protective against cyst relapse after
      excision. The objective of this systematic review was to assess the effect of
      long-term postoperative medical treatment on the risk of endometrioma recurrence.
      A MEDLINE search was conducted to identify all the comparative studies published
      in the last 12 years in the English language literature on the relation between
      long-term postoperative adjuvant therapy and risk of endometrioma recurrence. Of
      the 12 articles assessed in detail, four were finally selected based on surgery
      for endometriotic cysts, postoperative medical treatment use for >= 12 months vs.
      expectant management, and ultrasonographic and/or histological diagnosis of
      endometrioma recurrence. A total of 965 women were enrolled, 726 of whom were in
      three cohort studies and 239 in one randomized controlled trial. Oral
      contraceptives (OCs) were always used as postoperative adjuvant treatment. The
      absolute effect of postoperative OC use was assessed by comparing "always" and
      "never" users. A recurrent endometrioma was identified in 33 of 423 (8%) "always"
      OC users and in 117 of 341 (34%) women who underwent expectant management (pooled
      odds ratio 0.12; 95% confidence interval 0.05-0.29). To define the effect of
      duration of use, "always" users were compared with "ever" users, and "ever" with
      "never" users, with a pooled odds ratio of, respectively, 0.21 (95% confidence
      interval 0.11-0.40) and 0.39 (95% confidence interval 0.23-0.66). Postoperative
      OC use dramatically decreased the risk of ovarian endometrioma recurrence,
      especially in women who used OCs regularly and for prolonged periods.

PMID- 22646296
TI  - Psychiatry training in Europe: views from the trenches.
AB  - BACKGROUND: In the majority of European countries, postgraduate psychiatry
      training schemes are developed and evaluated by national bodies in accordance
      with national legislation. In order to harmonise training in psychiatry across
      Europe, the European Union of Medical Specialists (UEMS) issued a number of
      recommendations for effective implementation of training programs in psychiatry.
      AIMS: To describe the structure and quality assurance mechanisms of postgraduate
      psychiatric training in Europe. METHOD: The European Federation of Psychiatry
      Trainees (EFPT) conducted a survey, which was completed by the representatives of
      29 member national psychiatric associations. RESULTS: In most countries (N = 19),
      the duration of the training programme is 5 years or more. Twenty-six countries
      have adapted a basic training programme that includes the 'common trunk'
      (according to UEMS definition) or a modified version of it. In 25 countries,
      trainees are evaluated several times during their training with a final exam at
      the end. In 25 countries, official quality assurance mechanisms exist. However,
      results demonstrate great variations in their implementation. CONCLUSIONS:
      Overall, psychiatric training programmes and assessment methods are largely
      compatible with one another across Europe. Quality assurance mechanisms, however,
      vary significantly. These should receive adequate attention by national and
      international educational policy makers.

PMID- 22646297
TI  - Direct correlation of radiologic and cadaveric structures in a gross anatomy
      course.
AB  - BACKGROUND: Radiologic imaging is increasingly utilized as supplemental material
      in preclinical gross anatomy courses, but few studies have investigated its
      utility as a fully integrated instructional tool. AIMS: Establish the benefit of
      a teaching method that simultaneously correlates cadaveric and radiologic
      structures for learning human anatomy. METHOD: We performed a mixed-methods
      randomized controlled trial and one-way cross-over study comparing exam grades
      and subjective student perception in a gross anatomy course. The intervention
      consisted of daily direct correlation small group sessions in which students
      simultaneously identified and correlated radiologic and cadaveric structures. The
      control method utilized identical laboratory and teaching conditions but students
      did not simultaneously correlate structures. Spatial relationships of structures
      within each respective media (gross or radiologic) were emphasized in both
      groups. RESULTS: No significant differences in radiology, gross, or written exam
      scores were observed between the intervention and control groups. The cross-over
      group preferred the intervention and control methods equally. The correlation
      teaching sessions ranked equally with active dissection as the most important
      instructional components of the course. CONCLUSION: Direct, simultaneous
      correlation of radiologic and cadaveric structures did not affect exam scores or
      student preference but helped students understand anatomical concepts in
      comparison with other course components.

PMID- 22646298
TI  - From theory to actual practice: creation and application of milestones in an
      internal medicine residency program, 2004-2010.
AB  - BACKGROUND: In the USA, the Accreditation Council of Graduate Medical Education,
      Educational Innovations Project is a partner in reshaping residency training to
      meet increasingly complex systems of health care delivery. AIM: We describe the
      creation and implementation of milestones as a vehicle for translating
      educational theory into practice in preparing residents to provide safe,
      autonomous patient care. METHOD: Six program faculty leaders, all with advanced
      medical education training, met in an iterative process of developing,
      implementing, and modifying milestones until a final set were vetted. RESULTS: We
      first formed the profile of a Master Internist. We then translated it into
      milestone language and implemented its integration across the program. Thirty
      seven milestones were applied in all settings and rotations to reach explicit
      educational outcomes. We created three types of milestones: Progressive, build
      one on top of the other to mastery; additive, adding multiple behaviors together
      to culminate in mastery; and descriptive, using a proscribe set of complex,
      predetermined steps toward mastery. CONCLUSIONS: Using milestones, our program
      has enhanced an educational model into explicit, end of training goals. Milestone
      implementation has yielded positive results toward competency-based training and
      others may adapt our strategies in a similar effort.

PMID- 22646299
TI  - An evaluation of the '5 Minute Medicine' video podcast series compared to
      conventional medical resources for the internal medicine clerkship.
AB  - BACKGROUND: '5 Minute Medicine' (5MM) is a series of video podcasts, that in
      approximately 5 min, each explain a core objective of the internal medicine
      clerkship that all clinical clerks should understand. Video podcasts are
      accessible at www.5minutemedicine.com AIM: The aim of this study was to
      investigate how well received 5MM video podcasts are as an educational tool for
      clinical clerks to use while on call. METHODS: Clinical clerks rotating through
      their internal medicine clerkship rotation were asked to use the 5MM video
      podcasts or conventional resources to prepare themselves prior to seeing
      patients. Questionnaires were distributed to students to determine effectiveness,
      appropriateness and time-efficiency of the resources students used. RESULTS:
      Students almost unanimously strongly agreed or agreed that the 5MM video podcasts
      were effective learning tools, appropriate for clinical clerks and time
      efficient, more so than conventionally used resources. The vast majority of
      clerks selected the 5MM videos as their preferred resource of all resources
      available to them. Most clerks felt the 5MM videos were better than textbooks and
      conventional online resources. CONCLUSION: Video podcasts such as the 5MM videos
      are welcomed as educational tools and may have a role in the future of
      undergraduate medical education.

PMID- 22646300
TI  - Curriculum Navigator: aspiring towards a comprehensive package for curriculum
      planning.
AB  - BACKGROUND: Insightful frameworks for curriculum development were described in
      the literature. There is a need, however, to outline the approach we prefer,
      sometime unconsciously, in curriculum planning. AIMS: This article describes a
      novel conceptual framework called Curriculum Navigator, to explore our attitudes
      towards the current curriculum, focus of interest, perception of rules and
      resources, flexibility to reform, style of communication and pattern of decision
      making in curriculum-related issues. METHODS: The Curriculum Navigator integrates
      well-known approaches with 13 new ones into a comprehensive conceptual framework
      to explore the curriculum planning process and provides an original framework to
      plan and direct the route of curriculum development. This article provides a
      manual to use the inventory and further explains how to integrate Curriculum
      Navigator with other well-established frameworks to aspire towards a
      comprehensive package for curriculum development. RESULTS: The Curriculum
      Navigator analyses our approach to curriculum planning and design in 10
      dimensions. Each dimension is represented in a four-point continuum between two
      styles: lawyer/detective, bird's eye/ant's eye, non-human/human resources,
      bureaucratic/activist, dogmatic/fashionable, authoritative/collaborative decision
      making, spy/salesman, magician/mentor, shopping/crafting and public
      relations/quality assurance. CONCLUSION: This article draws a visual portray of
      curriculum planning, design, management and reform in a particular school in one
      illustration.

PMID- 22646301
TI  - The educational theory basis of team-based learning.
AB  - BACKGROUND: Health care providers require the ability to use critical thinking
      skills and work effectively in a team as a part of an overall set of
      competencies. Therefore, educational programs should use appropriate methods
      based in educational theory to effectively graduate learners with these
      abilities. Team-based learning (TBL) is a method that has been introduced in
      healthcare education to foster critical thinking skills while students work in
      high functioning teams. AIMS: This article will show how TBL follows the
      principles of constructivist learning theory. METHOD: The principles of
      constructivist learning theory are discussed in relation to the teaching method
      of team-based learning. The effectiveness of TBL in healthcare education is then
      reviewed. RESULTS: TBL is learner centered with the teacher acting as an expert
      facilitator and also provides students with opportunities to expose
      inconsistencies between their current understandings and new experiences thus
      stimulating development of new personal mental frameworks built upon previous
      knowledge. The learning is active using relevant problems and group interaction.
      Teamwork skills are strengthened by focused reflection on new experiences during
      the group sessions and on teamwork success by providing feedback to group
      members. CONCLUSION: Since these aspects are all essential components of
      constructivist educational theory, TBL is solidly grounded in the theory and is a
      promising method to strengthen healthcare education.

PMID- 22646302
TI  - Proxyfan acts as a neutral antagonist of histamine H3 receptors in the feeding
      related hypothalamic ventromedial nucleus.
AB  - BACKGROUND AND PURPOSE: Centrally acting histamine H(3) receptor ligands are
      proposed as potential treatments for obesity, although the value of inverse
      agonists at these receptors is still debated. Functional inhibition of H(3)
      autoreceptors activates neurones in a hypothalamic 'satiety' centre. The H(3)
      receptor antagonist, proxyfan was used as a tool to assess the action of
      histaminergic compounds in this model. EXPERIMENTAL APPROACH: We compared the
      actions of histamine on feeding with those of an H(3) receptor agonist (imetit)
      and inverse agonist (thioperamide) in rats and mice. Sites of action were
      identified by immunohistochemistry and the hypothalamic ventromedial nucleus
      (VMN) was investigated using electrophysiological techniques. KEY RESULTS:
      Central histamine or thioperamide decreased fast-induced feeding, whereas imetit
      increased feeding. Systemic thioperamide entered the brain to activate
      hypothalamic feeding centres and to reduce feeding without causing any adverse
      behaviours. Thioperamide activated neurones in the VMN through an action on
      histamine autoreceptors, whilst imetit had the opposite effect. Proxyfan
      administered alone did not affect either feeding or electrical activity. However,
      it blocked the actions of both thioperamide and imetit, acting as a neutral
      antagonist in this system. CONCLUSIONS AND IMPLICATIONS: The H(3) receptor
      inverse agonist, thioperamide, potently reduced appetite without adverse
      behavioural effects. This action was blocked by proxyfan, acting as a neutral
      antagonist in this model and, therefore, this compound is useful in determining
      the selectivity of H(3) receptor-directed drugs. A major action of thioperamide
      is through presynaptic autoreceptors, inducing stimulation by endogenous
      histamine of postsynaptic H(1 ) receptors on anorectic hypothalamic neurones.

PMID- 22646303
TI  - Time to failure of oral therapy in children with type 2 diabetes: a single center
      retrospective chart review.
AB  - There are no data in children with type 2 diabetes (T2D) regarding the durability
      of glycemic control with oral medication. Therefore, we assessed the likelihood
      of and time to failure of oral therapy in children and adolescents diagnosed with
      T2D. Charts of patients presenting to our large tertiary-care children's hospital
      between January 2000 and June 2007 with a new diagnosis of diabetes (n = 1625)
      were reviewed to identify those with T2D (n = 184). Subjects' initial therapy,
      hemoglobin A1c (HbA1c), body mass index, age, gender, and antibody status were
      documented, as well as subsequent therapies and HbA1c values, to determine
      whether baseline characteristics predicted future insulin dependence. Kaplan
      Meier survival curves and Cox proportional hazards analysis demonstrated time to
      failure of oral therapy. Eighty-nine patients remained on insulin throughout the
      study. Baseline characteristics that determined future insulin dependence
      included being placed on insulin initially, initial HbA1c and race (whites less
      likely to be insulin dependent at study conclusion). Patients who failed oral
      therapy were more often reported to be non-compliant or unable to tolerate
      metformin than those who continued on oral therapy. The median time to failure of
      oral therapy (metformin monotherapy in 84/95) was not significantly different for
      patients initially treated with oral therapy (42 months) and insulin (35 months).
      Thus, children with T2D appear to fail oral therapy more quickly than what is
      reported in adults. It is not yet known if improving compliance with treatment
      might allow more children to remain on oral medications.

PMID- 22646305
TI  - Usefulness of thrombelastography platelet mapping assay to measure the
      antiplatelet effect of P2Y(12) receptor inhibitors and high on-treatment platelet
      reactivity.

PMID- 22646306
TI  - A lack of correlation between mast cells, angiogenesis, and outcome in non-small
      cell lung cancer.
AB  - Although a direct association between mast cells and cancer tumors is generally
      accepted, the exact nature of this relationship appears contradictory. The aim of
      this study was to clarify the effect of mast cells on tumor angiogenesis and
      outcome in Non-small cell lung cancer (NSCLC) patients. The tissue specimens
      evaluated were from patients with NSCLC who had undergone resection with curative
      intent at the Medical University of Bialystok Hospital. Of the 90 patients
      studied, 67 were men. Average age at surgery was 59.68 years. Study population
      included 29 cases of adenocarcinoma, 44 cases of squamous cell carcinoma, and 17
      cases of large cell carcinoma. The authors counted mast cells and microvessels in
      tumor sections. Mast cells were observed in small groups around vessels and in
      the cancer parenchyma. At a magnification of 200*, the number of mast cells was
      28.90 +/- 16.6. Intramural microvessels in endothelial cells were found in small
      groups, mostly at the margin. At a magnification of 200*, the number of
      microvessels was 221.69 +/- 120.36. Spearman correlation was observed in patients
      with adenocarcinoma, and also in patients with stage II disease. This study did
      not show correlation between mast cells count and survival rate, and correlation
      between microvessel count and survival rate. In this study, mast cells
      infiltration of the tumor islets was not associated with patients' survival. The
      authors did not find correlation between mast cells count and angiogenesis,
      except only in patients with adenocarcinoma, and in patients with stage II
      disease.

PMID- 22646304
TI  - Stillbirths and newborn deaths in slum settlements in Mumbai, India: a
      prospective verbal autopsy study.
AB  - BACKGROUND: Three million babies are stillborn each year and 3.6 million die in
      the first month of life. In India, early neonatal deaths make up four-fifths of
      neonatal deaths and infant mortality three-quarters of under-five mortality.
      Information is scarce on cause-specific perinatal and neonatal mortality in urban
      settings in low-income countries. We conducted verbal autopsies for stillbirths
      and neonatal deaths in Mumbai slum settlements. Our objectives were to classify
      deaths according to international cause-specific criteria and to identify major
      causes of delay in seeking and receiving health care for maternal and newborn
      health problems. METHODS: Over two years, 2005-2007, births and newborn deaths in
      48 slum areas were identified prospectively by local informants. Verbal autopsies
      were collected by trained field researchers, cause of death was classified by
      clinicians, and family narratives were analysed to investigate delays on the
      pathway to mortality. RESULTS: Of 105 stillbirths, 65 were fresh (62%) and
      obstetric complications dominated the cause classification. Of 116 neonatal
      deaths, 87 were early and the major causes were intrapartum-related (28%),
      prematurity (23%), and severe infection (22%). Bereavement was associated with
      socioeconomic quintile, previous stillbirth, and number of antenatal care visits.
      We identified 201 individual delays in 121/187 birth narratives (65%). Overall,
      delays in receiving care after arrival at a health facility dominated and were
      mostly the result of referral from one institution to another. Most delays in
      seeking care were attributed to a failure to recognise symptoms of complications
      or their severity. CONCLUSIONS: In Mumbai's slum settlements, early neonatal
      deaths made up 75% of neonatal deaths and intrapartum-related complications were
      the greatest cause of mortality. Delays were identified in two-thirds of
      narratives, were predominantly related to the provision of care, and were often
      attributable to referrals between health providers. There is a need for clear
      protocols for care and transfer at each level of the health system, and an
      emphasis on rapid identification of problems and communication between health
      facilities. TRIAL REGISTRATION: ISRCTN96256793.

PMID- 22646307
TI  - Insight into the structure of photosynthetic LH2 aggregate from spectroscopy
      simulations.
AB  - Using the electrostatic model of intermolecular interactions, we obtain the
      Frenkel exciton Hamiltonian parameters for the chlorophyll Qy band of a
      photosynthetic peripheral light harvesting complex LH2 of a purple bacteria
      Rhodopseudomonas acidophila from structural data. The intermolecular couplings
      are mostly determined by the chlorophyll relative positions, whereas the
      molecular transition energies are determined by the background charge
      distribution of the whole complex. The protonation pattern of titratable residues
      is used as a tunable parameter. By studying several protonation state scenarios
      for distinct protein groups and comparing the simulated absorption and circular
      dichroism spectra to experiment, we determine the most probable configuration of
      the protonation states of various side groups of the protein.

PMID- 22646309
TI  - Supra-molecular ecobionanocomposites based on polylactide and cellulosic
      nanowhiskers: synthesis and properties.
AB  - Successful filler dispersion and establishment of good interfacial contact with
      the surrounding matrix are essential for optimized reinforcement in polymeric
      nanocomposites. In particular, in renewable-based composites this can be
      challenging, where hydrophilic attractions between nanofillers facilitate
      aggregation. Here an innovative approach to prepare cellulosic nanowhisker (CNW)
      reinforced polylactide (PLA) is presented. The lactide ring-opening
      polymerization is initiated from CNW surface hydroxyl groups after partial
      acetylation to control the grafting density. Grafting of PLA chains is verified
      by Fourier transform infrared spectroscopy. The resulting nanocomposites display
      exceptional properties; a heat distortion temperature of 120  degrees C is
      achieved at 10 wt % CNW loading and can be further enhanced to reach 150  degrees
      C at 15 wt % CNW. The formation of a percolating network is verified by
      comparison of modulus data with an established theoretical model. Additionally,
      nucleation by CNWs reduces the crystallization half-time to 15 s compared with 90
      s for PLA. Melt-pressed films retain transparency indicating good filler
      dispersion.

PMID- 22646308
TI  - Sequence analysis for detection of first-line drug resistance in Mycobacterium
      tuberculosis strains from a high-incidence setting.
AB  - BACKGROUND: Drug resistance displays a problem for the therapy of Mycobacterium
      tuberculosis infections. For molecular resistance testing, it is essential to
      have precise knowledge on genomic variations involved in resistance development.
      However, data from high-incidence settings are only sparely available. Therefore
      we performed a systematic approach and analyzed a total of 97 M. tuberculosis
      strains from previously treated patients in Sierra Leone for mutations in katG,
      rpoB, rrs, rpsL, gidB, embB, pncA and where applicable in inhA and ahpC. Of the
      strains investigated 50 were either mono- or poly-resistant to isoniazid,
      rifampin, streptomycin, ethambutol and pyrazinamide or MDR and 47 fully
      susceptible strains served as controls. RESULTS: The majority of isoniazid and
      rifampin resistant strains had mutations in katG315 (71.9%) and rpoB531 (50%).
      However, rpoB mutations in codons 511, 516 and 533 were also detected in five
      rifampin susceptible strains. MIC determinations revealed low-level rifampin
      resistance for those strains. Thus, the sensitivity and specificity of sequencing
      of katG for detection of drug resistance were 86.7% and 100% and for sequencing
      of rpoB 100% and 93.8%, respectively.Strikingly, none of the streptomycin
      resistant strains had mutations in rrs, but 47.5% harboured mutations in rpsL.
      Further changes were detected in gidB. Among ethambutol resistant strains 46.7%
      had mutations at embB306. Pyrazinamide resistant strains displayed a variety of
      mutations throughout pncA. The specificities of sequencing of rpsL, embB and pncA
      for resistance detection were high (96-100%), whereas sensitivities were lower
      (48.8%, 73.3%, 70%). CONCLUSIONS: Our study reveals a good correlation between
      data from molecular and phenotypic resistance testing in this high-incidence
      setting. However, the fact that particular mutations in rpoB are not linked to
      high-level resistance is challenging and demonstrates that careful interpretation
      of molecular resistance assays is mandatory. In addition, certain variations,
      especially in gidB, appear to be phylogenetically informative polymorphisms
      rather than markers for drug resistance.

PMID- 22646310
TI  - Human bone marrow-derived mesenchymal stem cells produced TGFbeta contributes to
      progression and metastasis of prostate cancer.
AB  - Human mesenchymal stem cells (hMSCs) play an important role in the development of
      human cancers. In the present study, we observed that hMSCs promoted human
      prostate cancer (PCa) cell PC-3 growth in vivo and in vitro. The conditional
      medium of hMSCs promoted the proliferation, migration, and invasion of PC-3
      cells. The expression of MMP-2 and MMP-9 in PC-3 was upregulated by conditional
      medium of hMSCs. In addition, blocking tumor transformation factor beta (TGFbeta)
      blunted the pro-oncogenic function of hMSCs. These results suggest that hMSCs may
      play a pro-oncogenic role in the growth of human prostate caner by producing
      TGFbeta.

PMID- 22646311
TI  - Chemical control of semiconductor nanowire kinking and superstructure.
AB  - We show that methylgermane (GeH(3)CH(3)) can induce a transition from 111 to 110
      oriented growth during the vapor-liquid-solid synthesis of Ge nanowires. This
      hydride-based chemistry is subsequently leveraged to rationally fabricate kinking
      superstructures based on combinations of 111 and 110 segments. The addition of
      GeH(3)CH(3) also eliminates sidewall tapering and enables Ge nanowire growth at
      temperatures exceeding 475  degrees C, which greatly expands the process window
      and opens new avenues to create Si/Ge heterostructures.

PMID- 22646312
TI  - Creating water vapor barrier coatings from hydrophilic components.
AB  - The preparation of water vapor barrier coatings composed of polyelectrolyte/clay
      multilayers using the layer-by-layer technique is reported. The suitability of
      different synthetic and renewable polyelectrolytes for the preparation of barrier
      coatings in combination with montmorillonite (MMT) platelets as well as the
      influence of the ionic strength and the number of bilayers on the coating
      performance was investigated. Highly hydrophilic and permeable cellulose films
      were used as substrate for determining the influence of the coatings on the water
      vapor transmission rate (WVTR). Improved barrier properties were realized by the
      use of polyethylene imine (PEI) or 2-hydroxy-3-trimethylammonium propyl chloride
      starch (HPMA starch) in combination with MMT. After the application of only 5
      bilayers of PEI and MMT (thickness ~40 nm) on each side of the cellulose film,
      the WVTR was significantly reduced. By the deposition of 40 PEI/MMT bilayers, the
      WVTR transmission rate was reduced by 68%. However, HPMA starch containing
      coatings led to vapor transmission reduction of up to 32% at the same number of
      coating steps. A strong correlation between the barrier properties of the
      coatings and the layer thickness was observed. The barrier properties of the
      coatings could be increased using higher ionic strengths. These results represent
      unprecedented water vapor barrier properties for coatings prepared from
      hydrophilic materials. 

PMID- 22646314
TI  - Pharmacological dosage concepts: how useful are they for educators and speech
      language pathologists?
AB  - The first part of this response to Baker (2012) examines studies that have
      attempted to determine the optimum treatment intensity of reading interventions
      associated with a Response to Intervention (RTI) model of service delivery. In
      general, the findings indicated that differences in broad measures of intensity
      (duration and scheduling) did not result in differences in reading outcomes.
      These non-significant findings and Baker's excellent discussion of all of the
      factors that impact treatment outcomes led me to question how useful
      pharmacological dosage concepts are for educators and speech-language
      pathologists (SLPs). This commentary concludes by acknowledging that the more
      information available about the active ingredients of treatment episodes, the
      better able one will be to design effective and efficient interventions to
      improve speech, language, and literacy.

PMID- 22646313
TI  - Computational challenges and human factors influencing the design and use of
      clinical research participant eligibility pre-screening tools.
AB  - BACKGROUND: Clinical trials are the primary mechanism for advancing clinical care
      and evidenced-based practice, yet challenges with the recruitment of participants
      for such trials are widely recognized as a major barrier to these types of
      studies. Data warehouses (DW) store large amounts of heterogenous clinical data
      that can be used to enhance recruitment practices, but multiple challenges exist
      when using a data warehouse for such activities, due to the manner of collection,
      management, integration, analysis, and dissemination of the data. A critical step
      in leveraging the DW for recruitment purposes is being able to match trial
      eligibility criteria to discrete and semi-structured data types in the data
      warehouse, though trial eligibility criteria tend to be written without concern
      for their computability. We present the multi-modal evaluation of a web-based
      tool that can be used for pre-screening patients for clinical trial eligibility
      and assess the ability of this tool to be practically used for clinical research
      pre-screening and recruitment. METHODS: The study used a validation study,
      usability testing, and a heuristic evaluation to evaluate and characterize the
      operational characteristics of the software as well as human factors affecting
      its use. RESULTS: Clinical trials from the Division of Cardiology and the
      Department of Family Medicine were used for this multi-modal evaluation, which
      included a validation study, usability study, and a heuristic evaluation. From
      the results of the validation study, the software demonstrated a positive
      predictive value (PPV) of 54.12% and 0.7%, respectively, and a negative
      predictive value (NPV) of 73.3% and 87.5%, respectively, for two types of
      clinical trials. Heuristic principles concerning error prevention and
      documentation were characterized as the major usability issues during the
      heuristic evaluation. CONCLUSIONS: This software is intended to provide an
      initial list of eligible patients to a clinical study coordinators, which
      provides a starting point for further eligibility screening by the coordinator.
      Because this software has a high "rule in" ability, meaning that it is able to
      remove patients who are not eligible for the study, the use of an automated tool
      built to leverage an existing enterprise DW can be beneficial to determining
      eligibility and facilitating clinical trial recruitment through pre-screening.
      While the results of this study are promising, further refinement and study of
      this and related approaches to automated eligibility screening, including
      comparison to other approaches and stakeholder perceptions, are needed and future
      studies are planned to address these needs.

PMID- 22646315
TI  - Effects of immediate feedback on learning auditory perceptual voice quality
      evaluation.
AB  - The study investigated the effect of immediate feedback in training listeners to
      perceive subtle differences in voice quality, a perceptual skill that is
      important for speech-language pathologists. Sixty naive listeners were randomly
      assigned to a feedback group (Group F), a no feedback group (Group NF), and a no
      training group acting as a control group (Group C). The task was to evaluate the
      severity of a perceptual voice quality (breathiness) by using a reference
      matching paradigm. All participants took part in three rating sessions (pre
      training, 2 days after training and 1 week after training). Group F and Group NF
      participated in a training session immediately after the first rating session,
      where Group F practiced with immediate feedback given and Group NF practice with
      no immediate feedback given. The results showed that Group F and Group NF had
      significant improvement after training, but Group F did not retain the
      improvement in the third rating session. The use of a reference-matching training
      paradigm without giving frequent immediate feedback is suggested for auditory
      perceptual voice evaluation training. The most effective frequency of immediate
      feedback is yet to be determined.

PMID- 22646316
TI  - Studying the impact of intensity is important but complicated.
AB  - This commentary suggests that the most commonly studied aspect intensity (dose
      frequency) on overall rate of response to treatment may often be weak or
      conditional. To improve statistical power of tests of weak effects additive
      statistical models have typically been used. However, multiplicative models may
      be a more productive route to understanding dose frequency effects on children's
      speech and language development. To illustrate, recent findings are presented
      that dose frequency effects on vocabulary development varied by two child
      characteristics. Finally, it is suggested that spacing of teaching episodes
      within an intervention session be included as a variable in the multi-dimensional
      model of treatment intensity. Spacing teaching episodes may eventually prove to
      be one of the more powerful aspects of intensity.

PMID- 22646317
TI  - Effects of vicariant barriers, habitat stability, population isolation and
      environmental features on species divergence in the south-western Australian
      coastal reptile community.
AB  - Identifying explicit hypotheses regarding the factors determining genetic
      structuring within species can be difficult, especially in species distributed in
      historically dynamic regions. To contend with these challenges, we use a
      framework that combines species distribution models, environmental data and multi
      locus genetic data to generate and explore phylogeographic hypotheses for reptile
      species occupying the coastal sand-dune and sand-plain habitats of the south
      western Australian biodiversity hotspot, a community which has both a high
      diversity of endemics and has varied dramatically in spatial extent over time. We
      use hierarchical amova, summary statistic and distance-based analyses to
      explicitly test specific phylogeographic hypotheses. Namely, we test if
      biogeographic vicariance across barriers, habitat stability, population isolation
      along a linear habitat or fragmentation across different environments can explain
      genetic divergence within five co-distributed squamate reptile species. Our
      results show that patterns of genetic variation reflect complex and species
      specific interactions related to the spatial distribution of habitats present
      currently and during repeated glacial minima, as opposed to being associated with
      historical factors such as habitat stability between glacial and inter-glacial
      periods or vicariant barriers. We suggest that the large impact of habitat
      characteristics over time (i.e. relative levels of habitat connectivity, climatic
      gradients and spatial heterogeneity of soil types) reflects the ecological
      restrictions of the sand-dune and sand-plain reptile communities and may explain
      the lack of concordance across taxa. The study demonstrates the general utility
      of the approach for assemblage-level, as well as single species, phylogeographic
      study, including its usefulness for exploring biologically informed hypotheses
      about what factors have influenced patterns of genetic variation.

PMID- 22646318
TI  - Exploring the evolution of protein function in Archaea.
AB  - BACKGROUND: Despite recent progress in studies of the evolution of protein
      function, the questions what were the first functional protein domains and what
      were their basic building blocks remain unresolved. Previously, we introduced the
      concept of elementary functional loops (EFLs), which are the functional units of
      enzymes that provide elementary reactions in biochemical transformations. They
      are presumably descendants of primordial catalytic peptides. RESULTS: We analyzed
      distant evolutionary connections between protein functions in Archaea based on
      the EFLs comprising them. We show examples of the involvement of EFLs in new
      functional domains, as well as reutilization of EFLs and functional domains in
      building multidomain structures and protein complexes. CONCLUSIONS: Our analysis
      of the archaeal superkingdom yields the dominating mechanisms in different
      periods of protein evolution, which resulted in several levels of the
      organization of biochemical function. First, functional domains emerged as
      combinations of prebiotic peptides with the very basic functions, such as
      nucleotide/phosphate and metal cofactor binding. Second, domain recombination
      brought to the evolutionary scene the multidomain proteins and complexes. Later,
      reutilization and de novo design of functional domains and elementary functional
      loops complemented evolution of protein function.

PMID- 22646319
TI  - Can simulation replace part of clinical time? Two parallel randomised controlled
      trials.
AB  - CONTEXT: Education in simulated learning environments (SLEs) has grown rapidly
      across health care professions, yet no substantive randomised controlled trial
      (RCT) has investigated whether SLEs can, in part, substitute for traditional
      clinical education. METHODS: Participants were physiotherapy students (RCT 1, n =
      192; RCT 2, n = 178) from six Australian universities undertaking clinical
      education in an ambulatory care setting with patients with musculoskeletal
      disorders. A simulated learning programme was developed as a replica for clinical
      education in musculoskeletal practice to replace 1 week of a 4-week clinical
      education placement. Two SLE models were designed. Model 1 provided 1 week in the
      SLE, followed by 3 weeks in clinical immersion; Model 2 offered training in the
      SLE in parallel with clinical immersion during the first 2 weeks of the 4-week
      placement. Two single-blind, multicentre RCTs (RCT 1, Model 1; RCT 2, Model 2)
      were conducted using a non-inferiority design to determine if the clinical
      competencies of students part-educated in SLEs would be any worse than those of
      students educated fully in traditional clinical immersion. The RCTs were
      conducted simultaneously, but independently. Within each RCT, students were
      stratified on academic score and randomised to either the SLE group or the
      control ('Traditional') group, which undertook 4 weeks of traditional clinical
      immersion. The primary outcome measure was a blinded assessment of student
      competency conducted over two clinical examinations at week 4 using the
      Assessment of Physiotherapy Practice (APP) tool. RESULTS: Students' achievement
      of clinical competencies was no worse in the SLE groups than in the Traditional
      groups in either RCT (Margin [Delta] >= 0.4 difference on APP score; RCT 1: 95%
      CI - 0.07 to 0.17; RCT 2: 95% CI - 0.11 to 0.16). CONCLUSIONS: These RCTs provide
      evidence that clinical education in an SLE can in part (25%) replace clinical
      time with real patients without compromising students' attainment of the
      professional competencies required to practise.

PMID- 22646321
TI  - Identification of the novel HLA allele, HLA-B*40:159, in a Taiwanese
      hematopoietic stem cell donor and the probable HLA haplotype in an association
      with B*40:159.
AB  - Using a sequence-based typing method, we found a new HLA-B*40 variant, B*40:159,
      in a Taiwanese hematopoietic stem cell donor. The sequence of B*40:159 is
      identical to the sequence of B*40:06:01:01 in exons 2 and 3 except the
      nucleotides at positions 412 (A -> G) and 429 (A -> C). The sequence variation
      caused two amino acid exchanges at residue 114 (N -> D) and residue 116 (Y -> S).
      The probable HLA-A, HLA-B, HLA-C and HLA-DRB1 haplotype in association with
      B*40:159 may be deduced as HLA-A*02:06-B*40:159-C*08:01-DRB1*08:03. The
      generation of B*40:159 is thought as the result of a sequence recombination event
      where B*46:01:01:01, B*15:01:01 or B*15:02:01 donated a minimum length of the DNA
      sequence from residue 412 to residue 419 to the recipient sequence of
      B*40:06:01:01.

PMID- 22646320
TI  - Cryptococcus neoformans phospholipase B1 activates host cell Rac1 for traversal
      across the blood-brain barrier.
AB  - Cryptococcus neoformans penetration into the central nervous system (CNS)
      requires traversal of the blood-brain barrier that is composed of a single layer
      of human brain microvascular endothelial cells (HBMEC), but the underlying
      mechanisms of C. neoformans traversal remain incompletely understood. C.
      neoformans transcytosis of HBMEC monolayer involves rearrangements of the host
      cell actin cytoskeleton and small GTP-binding Rho family proteins such as Rac1
      are shown to regulate host cell actin cytoskeleton. We, therefore, examined
      whether C. neoformans traversal of the blood-brain barrier involves host Rac1.
      While the levels of activated Rac1 (GTP-Rac1) in HBMEC increased significantly
      upon incubation with C. neoformans strains, pharmacological inhibition and down
      modulation of Rac1 significantly decreased C. neoformans transcytosis of HBMEC
      monolayer. Also, Rac1 inhibition was efficient in preventing C. neoformans
      penetration into the brain. In addition, C. neoformans phospholipase B1 (Plb1)
      was shown to contribute to activating host cell Rac1, andSTAT3 was observed to
      associate with GTP-Rac1 in HBMEC that were incubated with C. neoformans strain
      but not with its Deltaplb1 mutant. These findings demonstrate for the first time
      that C. neoformans Plb1 aids fungal traversal across the blood-brain barrier by
      activating host cell Rac1 and its association with STAT3, and suggest that
      pharmacological intervention of host-microbial interaction contributing to
      traversal of the blood-brain barrier may prevent C. neoformans penetration into
      the brain.

PMID- 22646322
TI  - The role of anti-Mullerian hormone in female fertility and infertility - an
      overview.
AB  - Anti-Mullerian hormone (AMH) plasma levels reflect the continuous non-cyclic
      growth of small follicles, thereby mirroring the size of the resting primordial
      follicle pool and thus acting as a useful marker of ovarian reserve. Anti
      Mullerian hormone seems to be the best endocrine marker for assessing the age
      related decline of the ovarian pool in healthy women; thus, it has a potential
      ability to predict future reproductive lifespan. The most established role for
      AMH measurements is before in vitro fertilization is initiated, because AMH can
      be predictive of the ovarian response, namely poor and hyper-responses. However,
      recent research has also highlighted the use of AMH in a variety of ovarian
      pathological conditions, including polycystic ovary syndrome, granulosa cell
      tumors and premature ovarian failure. A new commercial enzyme-linked
      immunosorbent assay for measuring AMH levels has been developed, making results
      from different studies more comparable. Nevertheless, widespread clinical
      application awaits an international standard for AMH, so that results using
      future assays can be reliably compared.

PMID- 22646469
TI  - Mean platelet volume in biopsy-proven non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as the most
      common cause of chronic liver disease worldwide. It has been shown that NAFLD has
      a strong association with metabolic syndrome and its component like insulin
      resistance (IR). Cardiovascular disease has a relation with NAFLD. Platelet
      volume is an indicator of platelet function and activation. Mean platelet volume
      (MPV) has been reported as a risk factor for atherothrombosis. In our study, we
      aimed to investigate the relation of MPV with NAFLD and IR in the NAFLD patients.
      A total of 54 patients with histologically proven NAFLD and 41 healthy age
      matched control subject were enrolled in this study. The NAFLD subjects were
      divided into two subgroups: 42 patients in the insulin resistant group (median
      age 39.5, females 22 [52%]) and 12 patients in the insulin sensitive group
      (median age 38, females 5 [41.7%]). MPV were significantly higher in the NAFLD
      group in univariate analysis (p < 0.05). In the NAFLD patients, we did not find
      any relation between steatosis grade, lobular inflammation, hepatocellular
      ballooning, NAFLD activity score and fibrosis with MPV value. Among the insulin
      resistant and sensitive groups in the NAFLD patients MPV values were similar. The
      results of this study showed that MPV, an indicator of platelet activation,
      increased in biopsy proven NAFLD patients but MPV is not correlated with the
      increase of IR in NAFLD patients. MPV is not related with inflammation and
      steatosis degree, hepatocellular ballooning and fibrosis in NAFLD patients.

PMID- 22646470
TI  - Selective acceleration of the protonated merocyanine-spiropyran photochromic
      transformation by inclusion in cucurbit[7]uril.
AB  - The effect of cucurbit[7]uril (CB7) on the spiropyran-merocyanine photochromic
      interconversion was studied in acidic and alkaline aqueous solutions. The
      merocyanine (MC) isomer was found to be the thermodynamically most stable form
      both in water and in the presence of CB7. A preferential binding of the
      protonated merocyanine (MCH(+)) to CB7 was observed with an equilibrium constant
      of 7.4*10(4) m(-1), and the complex formation led to significant diminution of
      acidity of the guest. The photoinduced transformation of MCH(+) to the spiropyran
      isomer was accelerated 2.3-fold upon addition of CB7, whereas the rates of the
      other photochromic processes were not affected. The partial inclusion of MCH(+)
      in CB7 led to dual fluorescence due to the incomplete deprotonation in the
      singlet-excited state.

PMID- 22646471
TI  - The effects of retinoids on secondary wound healing: biometrical and
      histopathological study in rats.
AB  - OBJECTIVE: A wound healing is a complex process, and the role of retinoids in
      this process is debated and controversial. In this study, the effect of topical
      tretinoin and oral acitretin on wound healing process was investigated in full
      thickness skin lesions on rat model. METHOD: A circular full-thickness wound was
      created by 6 mm punch biopsy on the back side of 32 male rats. The rats were
      seperated into four equal. The first group was assigned as a control group and
      was observed with no treatment. The second group was administered dexpanthenol
      once a day over wound area. In the third group, 0.1% tretinoin cream was applied
      daily. In the fourth group, 2.5 mg/kg/day acitretin was given daily.
      Additionally, the biopsies were taken from wounds for the histopathologic
      examination. RESULTS: The complete recovery time was remarkably longer in the
      tretionin group than the control group and the dexpantenol group (p < 0.05). The
      average complete recovery time was significantly longer in the acitretin group
      than the control and dexpanthenol groups whereas it was statistically shorter in
      the acitrein group than the tretionin group (p < 0.05). CONCLUSION: Based on our
      findings, topical tretinoin and oral acitretin can delay secondary wound healing,
      epithelization and angiogenesis.

PMID- 22646472
TI  - Role of intercellular adhesion molecule-2 in osteoclastogenesis.
AB  - Osteoclasts, multinucleated bone-resorbing cells, are specialized cells derived
      from the monocyte/macrophage lineage. Therefore, it is essential for mononuclear
      precursors to find a fusion partner during its differentiation. Our previous
      study showed an important role of cell communication via Mac-1 (CD11b/CD18)
      during osteoclastogenesis. However, the counter receptor of Mac-1 was still
      unknown. Flow cytometric analysis showed that bone marrow-derived mononuclear
      cells, used as osteoclast precursors, expressed intercellular adhesion molecule-1
      and -2. Quantitative RT-PCR analysis revealed that expression level of ICAM-2 was
      higher than that of ICAM-1 in bone marrow cells. The osteoclastogenesis induced
      by receptor activator of NF-kappaB ligand (RANKL) was inhibited by anti-ICAM-2
      neutralizing antibody but not by anti-ICAM-1 neutralizing antibody. The
      inhibitory effect of anti-ICAM-2 antibody on osteoclastogenesis was enhanced by
      simultaneous treatment of anti-CD11b neutralizing antibody. Furthermore,
      osteoclastogenesis induced by tumor necrosis factor alpha (TNFalpha) was also
      inhibited by anti-ICAM-2 neutralizing antibody. The involvement of lymphocytes in
      osteoclastogenesis was excluded, because anti-ICAM-2 antibody inhibited
      osteoclastogenesis using bone marrow-derived cells from immunodeficiency mice.
      Immunocytochemical staining demonstrated colocalization of ICAM-2 and Mac-1
      during osteoclastogenesis; however, Mac-1 immunoreactivity was lost in
      differentiated multinucleated osteoclast. These results suggest the important
      role of ICAM-2/Mac-1 binding in osteoclastogenesis induced by either RANKL or
      TNFalpha.

PMID- 22646473
TI  - Budesonide inhibits interleukin-32 expression in a rat model of chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder
      of the lung, and is the fifth leading cause of morbidity worldwide. A novel
      proinflammatory factor, interleukine-32 (IL-32), is suggested as a risk factor of
      COPD. Budesonide is widely used for COPD treatment as anti-inflammatory drug.
      However, the inflammatory inhibition mechanism of budesonide is not fully
      understood. In this study, we used a rat model with COPD to investigate the
      effect of budesonide on IL-32 expression in lung tissue. We found that cigarette
      smoking (CS) strongly induced IL-32 expression in lung tissue, seriously weakened
      lung function, and damaged pulmonary tissue. Budesonide inhibited the expression
      of IL-32 in lung tissue. In budesonide-treated rats, we observed no repair of
      damaged lung tissue but the pulmonary function was partly recovered. To our
      knowledge, this is the first report that budesonide inhibits the expression of IL
      32 in lung tissues, which is strongly induced by CS.

PMID- 22646474
TI  - Rapid, covalent addition of phosphine to dithiolene in a molybdenum
      tris(dithiolene). A new structural model for dimethyl sulfoxide reductase.
AB  - Triphenylphosphine (PPh(3)) rapidly and reversibly adds to the bdt ligand in the
      molybdenum tris(dithiolene) complex Mo(tfd)(2)(bdt) [tfd = S(2)C(2)(CF(3))(2);
      bdt = S(2)C(6)H(4)], turning chelating bdt into the monodentate zwitterionic
      ligand SC(6)H(4)SPPh(3). A second PPh(3) molecule fills the newly created open
      site in the crystallographically characterized product
      Mo(tfd)(2)(SC(6)H(4)SPPh(3))(PPh(3)), which is a structural model for dimethyl
      sulfoxide (DMSO) reductase. While the complex is only a precatalyst for reduction
      of DMSO by PPh(3) (the initially low catalytic rate increases with time),
      Mo(tfd)(2)(SMe(2))(2) was found to be catalytically active without an induction
      period.

PMID- 22646476
TI  - Nanowire substrate-based laser scanning cytometry for quantitation of circulating
      tumor cells.
AB  - We report on the development of a nanowire substrate-enabled laser scanning
      imaging cytometry for rare cell analysis in order to achieve quantitative,
      automated, and functional evaluation of circulating tumor cells. Immuno
      functionalized nanowire arrays have been demonstrated as a superior material to
      capture rare cells from heterogeneous cell populations. The laser scanning
      cytometry method enables large-area, automated quantitation of captured cells and
      rapid evaluation of functional cellular parameters (e.g., size, shape, and
      signaling protein) at the single-cell level. This integrated platform was first
      tested for capture and quantitation of human lung carcinoma cells from a mixture
      of tumor cells and leukocytes. We further applied it to the analysis of rare
      tumor cells spiked in fresh human whole blood (several cells per mL) that emulate
      metastatic cancer patient blood and demonstrated the potential of this technology
      for analyzing circulating tumor cells in the clinical settings. Using a high
      content image analysis algorithm, cellular morphometric parameters and
      fluorescence intensities can be rapidly quantitated in an automated, unbiased,
      and standardized manner. Together, this approach enables informative
      characterization of captured cells in situ and potentially allows for
      subclassification of circulating tumor cells, a key step toward the
      identification of true metastasis-initiating cells. Thus, this nanoenabled
      platform holds great potential for studying the biology of rare tumor cells and
      for differential diagnosis of cancer progression and metastasis.

PMID- 22646475
TI  - Evaluating patient values and preferences for thromboprophylaxis decision making
      during pregnancy: a study protocol.
AB  - BACKGROUND: Pregnant women with prior venous thromboembolism (VTE) are at risk of
      recurrence. Low molecular weight heparin (LWMH) reduces the risk of pregnancy
      related VTE. LMWH prophylaxis is, however, inconvenient, uncomfortable, costly,
      medicalizes pregnancy, and may be associated with increased risks of obstetrical
      bleeding. Further, there is uncertainty in the estimates of both the baseline
      risk of pregnancy-related recurrent VTE and the effects of antepartum LMWH
      prophylaxis. The values and treatment preferences of pregnant women, crucial when
      making recommendations for prophylaxis, are currently unknown. The objective of
      this study is to address this gap in knowledge. METHODS: We will perform a multi
      center cross-sectional interview study in Canada, USA, Norway and Finland. The
      study population will consist of 100 women with a history of lower extremity deep
      vein thrombosis (DVT) or pulmonary embolism (PE), and who are either pregnant,
      planning pregnancy, or may in the future consider pregnancy (women between 18 and
      45 years). We will exclude individuals who are on full dose anticoagulation or
      thromboprophylaxis, who have undergone surgical sterilization, or whose partners
      have undergone vasectomy. We will determine each participant's willingness to
      receive LMWH prophylaxis during pregnancy through direct choice exercises based
      on real life and hypothetical scenarios, preference-elicitation using a visual
      analog scale ("feeling thermometer"), and a probability trade-off exercise. The
      primary outcome will be the minimum reduction (threshold) in VTE risk at which
      women change from declining to accepting LMWH prophylaxis. We will explore
      possible determinants of this choice, including educational attainment, the
      characteristics of the women's prior VTE, and prior experience with LMWH. We will
      determine the utilities that women place on the burden of LMWH prophylaxis,
      pregnancy-related DVT, pregnancy-related PE and pregnancy-related hemorrhage. We
      will generate a "personalized decision analysis" using participants' utilities
      and their personalized risk of recurrent VTE as inputs to a decision analytic
      model. We will compare the personalized decision analysis to the participant's
      stated choice. DISCUSSION: The preferences of pregnant women at risk of VTE with
      respect to the use of antithrombotic therapy remain unexplored. This research
      will provide explicit, quantitative expressions of women's valuations of health
      states related to recurrent VTE and its prevention with LMWH. This information
      will be crucial for both guideline developers and for clinicians.

PMID- 22646477
TI  - In vitro approach to assess the potential for risk of idiosyncratic adverse
      reactions caused by candidate drugs.
AB  - Idiosyncratic adverse drug reactions (IADRs) in humans can result in a broad
      range of clinically significant toxicities leading to attrition during drug
      development as well as postlicensing withdrawal or labeling. IADRs arise from
      both drug and patient related mechanisms and risk factors. Drug related risk
      factors, resulting from parent compound or metabolites, may involve multiple
      contributory mechanisms including organelle toxicity, effects related to compound
      disposition, and/or immune activation. In the current study, we evaluate an in
      vitro approach, which explored both cellular effects and covalent binding (CVB)
      to assess IADR risks for drug candidates using 36 drugs which caused different
      patterns and severities of IADRs in humans. The cellular effects were tested in
      an in vitro Panel of five assays which quantified (1) toxicity to THLE cells
      (SV40 T-antigen-immortalized human liver epithelial cells), which do not express
      P450s, (2) toxicity to a THLE cell line which selectively expresses P450 3A4, (3)
      cytotoxicity in HepG2 cells in glucose and galactose media, which is indicative
      of mitochondrial injury, (4) inhibition of the human bile salt export pump, BSEP,
      and (5) inhibition of the rat multidrug resistance associated protein 2, Mrp2. In
      addition, the CVB Burden was estimated by determining the CVB of radiolabeled
      compound to human hepatocytes and factoring in both the maximum prescribed daily
      dose and the fraction of metabolism leading to CVB. Combining the aggregated
      results from the in vitro Panel assays with the CVB Burden data discriminated,
      with high specificity (78%) and sensitivity (100%), between 27 drugs, which had
      severe or marked IADR concern, and 9 drugs, which had low IADR concern, we
      propose that this integrated approach has the potential to enable selection of
      drug candidates with reduced propensity to cause IADRs in humans.

PMID- 22646478
TI  - An emigration versus a globalization perspective of the Lebanese physician
      workforce: a qualitative study.
AB  - BACKGROUND: Lebanon is witnessing an increased emigration of physicians. The
      objective of this study was to understand the perceptions of Lebanese
      policymakers of this emigration, and elicit their proposals for future policies
      and strategies to deal with this emigration. METHODS: We conducted semi
      structured individual interviews with the deans of Lebanon's seven medical
      schools, the presidents of the two physicians professional associations, and
      governmental officials. We analyzed the results qualitatively. RESULTS:
      Participants differed in the assessment of the extent and gravity of emigration.
      Lebanon has a surplus of physicians, driven largely by the over-production of
      graduates by a growing number of medical schools. Participants cited advantages
      and disadvantages of the emigration on the personal, financial, medical education
      system, healthcare system, and national levels. Proposed strategies included
      limiting the number of students entering medical schools, creating job
      opportunities for graduating students, and implementing quality standards. Most
      participants acknowledged the globalization of the Lebanese physician workforce,
      including exchanges with the Gulf region, exchanges with developed countries, and
      the involvement of North American medical education institutions in the region.
      CONCLUSION: Many Lebanese policy makers, particularly deans of medical schools,
      perceive the emigration of the physician workforce as an opportunity in the
      context of the globalization of the profession.

PMID- 22646480
TI  - Diverse effects of cyclic AMP variants on osteogenic and adipogenic
      differentiation of human mesenchymal stromal cells.
AB  - Osteogenic differentiation of human mesenchymal stromal cells (hMSCs) may
      potentially be used in cell-based bone tissue-engineering applications to enhance
      the bone-forming potential of these cells. Osteogenic differentiation and
      adipogenic differentiation are thought to be mutually exclusive, and although
      several signaling pathways and cues that induce osteogenic or adipogenic
      differentiation, respectively, have been identified, there is no general
      consensus on how to optimally differentiate hMSCs into the osteogenic lineage.
      Some pathways have also been reported to be involved in both adipogenic and
      osteogenic differentiation, as for example, the protein kinase A (PKA) pathway,
      and the aim of this study was to investigate the role of cAMP/PKA signaling in
      differentiation of hMSCs in more detail. We show that activation of this pathway
      with dibutyryl-cAMP results in enhanced alkaline phosphatase expression, whereas
      another cAMP analog induces adipogenesis in long-term mineralization cultures.
      Adipogenic differentiation, induced by 8-bromo-cAMP, was accompanied by stronger
      PKA activity and higher expression of cAMP-responsive genes, suggesting that
      stronger activation correlates with adipogenic differentiation. In addition, a
      whole-genome expression analysis showed an increase in expression of adipogenic
      genes in 8-br-cAMP-treated cells. Furthermore, by means of quantitative
      polymerase chain reaction, we show differences in peroxisome proliferator
      activated receptor-gamma activation, either alone or in combination with
      dexamethasone, thus demonstrating differential effects of the PKA pathway, most
      likely depending on its mode of activation.

PMID- 22646479
TI  - MicroRNA-mRNA interactions in a murine model of hyperoxia-induced
      bronchopulmonary dysplasia.
AB  - BACKGROUND: Bronchopulmonary dysplasia is a chronic lung disease of premature
      neonates characterized by arrested pulmonary alveolar development. There is
      increasing evidence that microRNAs (miRNAs) regulate translation of messenger
      RNAs (mRNAs) during lung organogenesis. The potential role of miRNAs in the
      pathogenesis of BPD is unclear. RESULTS: Following exposure of neonatal mice to
      80% O2 or room air (RA) for either 14 or 29 days, lungs of hyperoxic mice
      displayed histological changes consistent with BPD. Comprehensive miRNA and mRNA
      profiling was performed using lung tissue from both O2 and RA treated mice,
      identifying a number of dynamically regulated miRNAs and associated mRNA target
      genes. Gene ontology enrichment and pathway analysis revealed that hyperoxia
      modulated genes involved in a variety of lung developmental processes, including
      cell cycle, cell adhesion, mobility and taxis, inflammation, and angiogenesis.
      MiR-29 was prominently increased in the lungs of hyperoxic mice, and several
      predicted mRNA targets of miR-29 were validated with real-time PCR, western
      blotting and immunohistochemistry. Direct miR-29 targets were further validated
      in vitro using bronchoalveolar stem cells. CONCLUSION: In newborn mice, prolonged
      hyperoxia induces an arrest of alveolar development similar to that seen in human
      neonates with BPD. This abnormal lung development is accompanied by significant
      increases in the levels of multiple miRNAs and corresponding decreases in the
      levels of predicted mRNA targets, many of which have known or suspected roles in
      pathways altered in BPD. These data support the hypothesis that dynamic
      regulation of miRNAs plays a prominent role in the pathophysiology of BPD.

PMID- 22646482
TI  - Complementation between inactive fragments of SssI DNA methyltransferase.
AB  - BACKGROUND: Silencing mammalian genes by targeted DNA (cytosine-5) methylation of
      selected CG sites in the genome would be a powerful technique to analyze
      epigenomic information and to study the roles of DNA methylation in physiological
      and pathological states. A promising approach of targeted DNA methylation is
      based on the ability of split fragments of a monomeric DNA methyltransferase (C5
      MTase) to associate and form active enzyme. A few C5-MTases of different
      specificities have been shown to possess the ability of fragment complementation,
      but a demonstration of this phenomenon for a C5-MTase, which has CG specificity
      and thus can be targeted to methylate any CG site, has been lacking. The purpose
      of this study was to test whether the CG-specific prokaryotic C5-MTase M.SssI
      shows the phenomenon of fragment complementation. RESULTS: We show that truncated
      inactive N-terminal fragments of M.SssI can assemble with truncated inactive C
      terminal fragments to form active enzyme in vivo when produced in the same E.
      coli cell. Overlapping and non-overlapping fragments as well as fragments
      containing short appended foreign sequences had complementation capacity. In
      optimal combinations C-terminal fragments started between conserved motif VIII
      and the predicted target recognizing domain of M.SssI. DNA methyltransferase
      activity in crude extracts of cells with the best complementing fragment pairs
      was ~ 4 per cent of the activity of cells producing the full length enzyme.
      Fusions of two N-terminal and two C-terminal fragments to 21.6 kDa zinc finger
      domains only slightly reduced complementation ability of the fragments.
      CONCLUSIONS: The CG-specific DNA methyltransferase M.SssI shows the phenomenon of
      fragment complementation in vivo in E. coli. Fusion of the split fragments to six
      unit zinc finger domains does not substantially interfere with the formation of
      active enzyme. These observations and the large number of complementing fragment
      combinations representing a wide range of MTase activity offer the possibility to
      develop M.SssI into a programmable DNA methyltransferase of high specificity.

PMID- 22646483
TI  - Self-injury and disordered eating: expressing emotion dysregulation through the
      body.
AB  - Previous research has suggested that emotion dysregulation, body-related
      concerns, and depressive symptoms are associated with nonsuicidal self-injury
      (NSSI) and disordered eating (DE) separately and in combination. However, it has
      been difficult to ascertain to what extent these constructs contribute to NSSI
      and DE given the relatively small number of studies examining their co
      occurrence, particularly among nonclinical samples. Based on responses to self
      report questionnaires, college-aged women who completed the study were divided
      into three groups: NSSI only; DE only; and NSSI + DE based on clinical cutoff
      criteria. Results support hypotheses that emotion dysregulation is a shared
      vulnerability and that body-related concerns and depression exhibit unique
      patterns of association across the three groups. It appears that NSSI is best
      understood as a response to negative affective states relative to DE, which is
      best understood as a set of behaviors motivated by body image concerns. The
      presence of both NSSI and DE is primarily influenced by emotion dysregulation and
      the dominant difficulties linked to each behavior; depression and body
      dissatisfaction. These findings suggest that treatment and prevention efforts
      should emphasize emotion regulation skills and differentially target body
      concerns or depressive symptoms according to the primary behavioral dysfunction
      that is present.

PMID- 22646484
TI  - Cell division and DNA segregation in Streptomyces: how to build a septum in the
      middle of nowhere?
AB  - Streptomycetes are antibiotic-producing filamentous microorganisms that have a
      mycelial life style. In many ways streptomycetes are the odd ones out in terms of
      cell division. While the basic components of the cell division machinery are
      similar to those found in rod-shaped bacteria such as Escherichia coli and
      Bacillus subtilis, many aspects of the control of cell division and its co
      ordination with chromosome segregation are remarkably different. The rather
      astonishing fact that cell division is not essential for growth makes these
      bacteria unique. The fundamental difference between the cross-walls produced
      during normal growth and sporulation septa formed in aerial hyphae, and the role
      of the divisome in their formation are discussed. We then take a closer look at
      the way septum site localization is regulated in the long and multinucleoid
      Streptomyces hyphae, with particular focus on actinomycete-specific proteins and
      the role of nucleoid segregation and condensation.

PMID- 22646481
TI  - Alzheimer's disease, beta-amyloid, glutamate, NMDA receptors and memantine-
      searching for the connections.
AB  - beta-amyloid (Abeta) is widely accepted to be one of the major pathomechanisms
      underlying Alzheimer's disease (AD), although there is presently lively debate
      regarding the relative roles of particular species/forms of this peptide. Most
      recent evidence indicates that soluble oligomers rather than plaques are the
      major cause of synaptic dysfunction and ultimately neurodegeneration. Soluble
      oligomeric Abeta has been shown to interact with several proteins, for example
      glutamatergic receptors of the NMDA type and proteins responsible for maintaining
      glutamate homeostasis such as uptake and release. As NMDA receptors are
      critically involved in neuronal plasticity including learning and memory, we felt
      that it would be valuable to provide an up to date review of the evidence
      connecting Abeta to these receptors and related neuronal plasticity. Strong
      support for the clinical relevance of such interactions is provided by the NMDA
      receptor antagonist memantine. This substance is the only NMDA receptor
      antagonist used clinically in the treatment of AD and therefore offers an
      excellent tool to facilitate translational extrapolations from in vitro studies
      through in vivo animal experiments to its ultimate clinical utility.

PMID- 22646486
TI  - Thermally evaporated SiO thin films as a versatile interlayer for plasma-based
      OLED passivation.
AB  - Silicon monoxide (SiO) thin films were introduced as an efficient interlayer for
      achieving plasma-based organic light-emitting diode (OLED) surface passivation.
      The SiO thin films could be consecutively formed via thermal evaporation, without
      breaking the vacuum, after deposition of the OLED cathode. The plasma resistivity
      and UV-blocking characteristics of the SiO interlayer protected the OLED devices
      against electrical and optical degradation during the plasma-enhanced atomic
      layer deposition (PEALD) and plasma-enhanced chemical vapor deposition (PECVD)
      passivation processes. In addition, the nonconformal deposition and hydroxyl
      group-rich surface characteristics of the SiO thin films yielded enhanced surface
      pinhole coverage and a higher initial film density in the subsequently deposited
      PEALD-based Al2O3 barrier film. As a result, the OLEDs with a SiO/Al2O3 bilayer
      passivation layer displayed a remarkably increased device shelf life compared to
      devices prepared using Al2O3-only passivation. A MOCON test showed that the water
      vapor transmission rate (WVTR) of the SiO/Al2O3 bilayer film was 0.0033 g/(m(2)
      day), 2.3 times lower than the rate of a single Al2O3 barrier film. The results
      of our study demonstrated the multipurpose role of a SiO interlayer in plasma
      based OLED passivation. The layer acted as a damage-free protective layer for the
      underlying OLED devices and an assistant layer to improve the upper barrier film
      performance. 

PMID- 22646485
TI  - Association between genetic variants in adhesion molecules and outcomes after
      hematopoietic cell transplants.
AB  - Allogeneic hematopoietic cell transplant (HCT) is associated with a high
      morbidity and mortality. Adhesion molecules play an important role in endothelial
      activation and initiation of inflammatory response. We hypothesized that single
      nucleotide polymorphisms (SNPs) in the endothelial molecules may contribute to
      heterogeneity in HCT outcomes. We evaluated the association of 4 SNPs in ICAM1
      (rs5498), PECAM1 (rs668 and rs1131012) and SELL (rs2229569) genes with acute and
      chronic graft-versus-host disease (GvHD) and those experiencing transplant
      related mortality (TRM) within 1 year among 425 allogeneic HCT recipient-donor
      pairs. Using a Fine and Gray proportional hazards model to evaluate the
      association between genetic variants and clinical outcomes, after adjustment for
      recipient age, race, diagnosis, disease status, gender mismatch, cytomegalovirus
      serostatus, gender, donor type, conditioning regimen and year of transplant, only
      rs5498 in the ICAM1 gene among both recipients and donors was associated with a
      decreased risk of TRM (P <= 0.02). None of the SNPs were associated with acute or
      chronic GvHD risk. These findings suggest that genetic variants in the vascular
      adhesion molecules may be used to identify patients at high risk for TRM.

PMID- 22646487
TI  - Transcriptional analysis of differentially expressed genes in response to stem
      inclination in young seedlings of pine.
AB  - The gravitropic response in trees is a widely studied phenomenon, however
      understanding of the molecular mechanism involved remains unclear. The purpose of
      this work was to identify differentially expressed genes in response to
      inclination using a comparative approach for two conifer species. Young seedlings
      were subjected to inclination and samples were collected at four different times
      points. First, suppression subtractive hybridisation (SSH) was used to identify
      differentially regulated genes in radiata pine (Pinus radiata D. Don). cDNA
      libraries were constructed from the upper and lower part of inclined stems in a
      time course experiment, ranging from 2.5 h to 1 month. From a total of 3092
      sequences obtained, 2203 elements were assembled, displaying homology to a public
      database. A total of 942 unigene elements were identified using bioinformatic
      tools after redundancy analysis. Of these, 614 corresponded to known function
      genes and 328 to unknown function genes, including hypothetical proteins.
      Comparative analysis between radiata pine and maritime pine (Pinus pinaster Ait.)
      was performed to validate the differential expression of relevant candidate genes
      using qPCR. Selected genes were involved in several functional categories:
      hormone regulation, phenylpropanoid pathway and signal transduction. This
      comparative approach for the two conifer species helped determine the molecular
      gene pattern generated by inclination, providing a set of Pinus gene signatures
      that may be involved in the gravitropic stress response. These genes may also
      represent relevant candidate genes involved in the gravitropic response and
      potentially in wood formation.

PMID- 22646488
TI  - Use of analgesic drugs and risk of ovarian cancer: results from a Danish case
      control study.
AB  - OBJECTIVE: The role of analgesic drug use in development of ovarian cancer is not
      fully understood. We examined the association between analgesic use and risk of
      ovarian cancer. In addition, we examined whether the association differed
      according to histological types. DESIGN: Population-based case-control study.
      SETTING: Denmark in the period 1995-1999. POPULATION: We included 756 women with
      epithelial ovarian cancer and 1564 randomly selected control women aged 35-79
      years. METHODS: Information on analgesic drug use was collected from personal
      interviews. Analgesic drugs were divided into the following categories: any
      analgesics; aspirin; non-aspirin non-steroidal anti-inflammatory drugs;
      paracetamol; and other analgesic drugs. The association between analgesic drug
      use and ovarian cancer risk was analysed using multiple logistic regression
      models. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. MAIN
      OUTCOME MEASURES: Epithelial ovarian cancer. RESULTS: Women with a regular use of
      any analgesics (OR = 0.79; 95% CI 0.62 - 1.01) or aspirin (OR = 0.68; 95% CI 0.46
      - 1.02) had a decreased risk of ovarian cancer, although not statistically
      significant. Regular use of non-aspirin non-steroidal anti-inflammatory drugs,
      paracetamol or other analgesics did not decrease ovarian cancer risk. Use of any
      analgesics (OR = 0.72; 95% CI 0.53-0.98) or aspirin (OR = 0.60; 95% CI 0.36-1.00)
      resulted in a statistically significant decreased risk of serous ovarian cancer
      but not mucinous or other ovarian tumors. CONCLUSION: In accordance with most
      previous studies, our results indicate a possible inverse association between
      analgesic use, particularly aspirin, and ovarian cancer risk.

PMID- 22646489
TI  - Analysis of US Veterans Health Administration comprehensive evaluations for
      traumatic brain injury in Operation Enduring Freedom and Operation Iraqi Freedom
      Veterans.
AB  - OBJECTIVE: To describe neurobehavioural symptoms in Iraq and Afghanistan war
      veterans evaluated for traumatic brain injury (TBI) through the Veterans Health
      Administration (VHA) TBI screening and evaluation programme. DESIGN: An
      observational study based on VHA administrative data for all veterans who
      underwent TBI Comprehensive Evaluation between October 2007 and June 2010.
      RESULTS: 55,070 predominantly white, non-Hispanic, male Veterans with a positive
      TBI screen had comprehensive TBI evaluations completed during the study period.
      Moderate-to-severe symptoms were common in the entire sample, both in those with
      and without a clinician-diagnosed TBI. However, the odds of reporting symptoms of
      this severity were significantly higher in those diagnosed with TBI compared to
      those without a TBI diagnosis, with odds ratios ranging from 1.35-2.21. TBI
      specialty clinicians believed that in the majority of diagnosed TBI cases both
      behavioural health conditions and TBI contributed to patients' symptom
      presentation. CONCLUSIONS: The VHAs TBI screening and evaluation process is
      identifying individuals with ongoing neurobehavioural symptoms. Moderate-to
      severe symptoms were more prevalent in veterans with TBI-specialty clinician
      determined TBI. However, the high rate of symptom reporting also present in
      individuals without a confirmed TBI suggest that symptom aetiology may be multi
      factorial in nature.

PMID- 22646490
TI  - Do blood collection methods influence whole-blood platelet function analysis?
AB  - Pre-analytical variables interact with standard coagulation parameters. How these
      variables affect the platelet function analysis is not completely known. How
      collection site and puncture method affect multiple electrode aggregometry (MEA)
      and platelet function analyzer (PFA-100(r)) was compared regarding contact
      activation. First, volunteers scheduled for elective cardiac surgery had blood
      collected from four lines: venous, arterial, central venous and by venipuncture.
      MEA and PFA-100(r) were analysed blinded for site origin. Second, two samples
      (citrate, Corn Trypsin Inhibitor, CTI) were collected in syringe or vacuum tubes.
      Thrombin generation (TG) was determined. MEA was triggered by adenosine
      diphosphate (ADP, 6.4 uM), arachidonic acid (ASPI, 0.5 mM), collagen (Col, 3.2
      ug/ml), ristocetin (Risto, 0.2 mg/ml) and thrombin receptor-activating peptide
      (TRAP, 32 uM). PFA-100(r) was triggered by collagen/epinephrine and collagen/ADP.
      TG was assessed in platelet-poor plasma with 1 pM tissue factor and 4 uM
      phospholipids and without trigger. Data were analysed using a two-way mixed
      effects model for the intraclass correlation (ICC) and by the Mann-Whitney U
      test. MEA and PFA-100(r) revealed good correlation (ICC) between the sites. CTI
      inhibited TG significantly more effective than citrate. Contact activation was
      independent of the collection method. Only the MEA ASPI test revealed significant
      differences between the two collection methods. Blood sampling from all lines for
      MEA and PFA-100(r) assays is justified. Contact activation is always present.
      Apparently this does not influence platelet function test results. Collection
      methods do not seem relevant, although, one should always consider using a
      standardized method.

PMID- 22646491
TI  - High viscosity of imidazolium ionic liquids with the hydrogen sulfate anion: a
      Raman spectroscopy study.
AB  - Ionic liquids based on 1-alkyl-3-methylimidazolium cations and the hydrogen
      sulfate (or bisulfate) anion, HSO(4)(-), are much more viscous than ionic liquids
      with alkyl sulfates, RSO(4)(-). The structural origin of the high viscosity of
      HSO(4)(-) ionic liquids is unraveled from detailed comparison of the anion Raman
      bands in 1-ethyl-3-methylimidazolium hydrogen sulfate and 1-butyl-3
      methylimidazolium hydrogen sulfate with available data for simple HSO(4)(-) salts
      in crystalline phase, molten phase, and aqueous solution. Two Raman bands at 1046
      and 1010 cm(-1) have been assigned as symmetric stretching modes nu(s)(S?O) of
      HSO(4)(-), the latter being characteristic of chains of hydrogen-bonded anions.
      The intensity of this component increases in the supercooled liquid phase. For
      comparison purposes, Raman spectra of 1-ethyl-3-methylimidazolium ethyl sulfate
      and 1-butyl-3-methylimidazolium methyl sulfate have been also obtained. There is
      no indication of difference in the strength of hydrogen bond interactions of
      imidazolium cations with HSO(4)(-) or RSO(4)(-) anions. Raman spectra at high
      pressures, up to 2.6 GPa, are also discussed. Raman spectroscopy provides
      evidence that hydrogen-bonded anions resulting in anion-anion interaction is the
      reason for the high viscosity of imidazolium ionic liquids with HSO(4)(-). If the
      ionic liquid is exposed to moisture, these structures are disrupted upon
      absorption of water from the atmosphere.

PMID- 22646492
TI  - Evaluation of the role of the new INNOVANCE PFA P2Y test cartridge in detection
      of clopidogrel resistance.
AB  - Light transmittance aggregometry (LTA) has been extensively used in monitoring
      clopidogrel therapy. However, the availability of simple and rapid point-of-care
      platelet function assays is of great clinical importance. Thus, the manufacturer
      of the Platelet Function Analyzer (PFA)-100 System has recently produced the
      INNOVANCE PFA P2Y test cartridge. We assessed the ability of this new test to
      reliably detect clopidogrel resistance. We enrolled 90 consecutive patients with
      coronary artery disease receiving chronic clopidogrel maintenance therapy in
      combination with aspirin. Twenty healthy volunteers served as controls.
      Clopidogrel resistance was simultaneously analysed by the INNOVANCE PFA P2Y test
      cartridge, ADP-induced LTA, the flow-cytometric vasodilator-stimulated
      phosphoprotein (VASP)-phosphorylation assay and the multiple electrode
      aggregometry (Multiplate). Agreement among the four platelet function methods by
      two was assessed using Cohen's kappa coefficient. According to the cut-off points
      for clopidogrel resistance proposed by the literature, agreement was fair between
      INNOVANCE PFA-100 P2Y and LTA (74.4%) and Multiplate (75.6%), while poor
      agreement was noticed in VASP assay (63.3%). Based on cut-off points indicating a
      higher thrombotic risk, agreement between the PFA-100 System and the other three
      methods did not significantly differ compared to the previous cut-offs (72.2%,
      71.1% and 55.1%, respectively). The INNOVANCE PFA-100 P2Y test seems to be
      comparable to other established platelet function assays in detecting clopidogrel
      resistance. However, the modest agreement among platelet function methods makes
      the performance of platelet function testing crucial with more than one technique
      in order to reliably identify poor responders to clopidogrel treatment.

PMID- 22646502
TI  - Climate oscillation during the Quaternary associated with landscape heterogeneity
      promoted allopatric lineage divergence of a temperate tree Kalopanax septemlobus
      (Araliaceae) in East Asia.
AB  - We investigated the biogeographic history of Kalopanax septemlobus, one of the
      most widespread temperate tree species in East Asia, using a combined
      phylogeographic and palaeodistribution modelling approach. Range-wide genetic
      differentiation at nuclear microsatellites (G'(ST) = 0.709; 2205 samples
      genotyped at five loci) and chloroplast DNA (G(ST) = 0.697; 576 samples sequenced
      for 2055 bp at three fragments) was high. A major phylogeographic break in
      Central China corresponded with those of other temperate species and the spatial
      delineation of the two temperate forest subkingdoms of East Asia, consistent with
      the forests having been isolated within both East and West China for multiple
      glacial-interglacial cycles. Evidence for multiple glacial refugia was found in
      most of its current range in China, South Japan and the southernmost part of the
      Korean Peninsula. In contrast, lineage admixture and absence of private alleles
      and haplotypes in Hokkaido and the northern Korean Peninsula support a
      postglacial origin of northernmost populations. Although palaeodistribution
      modelling predicted suitable climate across a land-bridge extending from South
      Japan to East China during the Last Glacial Maximum, the genetic differentiation
      of regional populations indicated a limited role of the exposed sea floor as a
      dispersal corridor at that time. Overall, this study provides evidence that
      differential impacts of Quaternary climate oscillation associated with landscape
      heterogeneity have shaped the genetic structure of a wide-ranging temperate tree
      in East Asia.

PMID- 22646504
TI  - UV-B radiation: from generic stressor to specific regulator.

PMID- 22646503
TI  - Chlamydial infection induces host cytokinesis failure at abscission.
AB  - Chlamydia trachomatis is an obligate intracellular bacteria and the infectious
      agent responsible for the sexually transmitted disease Chlamydia. Infection with
      Chlamydia can lead to serious health sequelae such as pelvic inflammatory disease
      and reproductive tract scarring contributing to infertility and ectopic
      pregnancies. Additionally, chlamydial infections have been epidemiologically
      linked to cervical cancer in patients with a prior human papilomavirus (HPV)
      infection. Chlamydial infection of cultured cells causes multinucleation, a
      potential pathway for chromosomal instability. Two mechanisms that are known to
      initiate multinucleation are cell fusion and cytokinesis failure. This study
      demonstrates that multinucleation of the host cell by Chlamydia is entirely due
      to cytokinesis failure. Moreover, cytokinesis failure is due in part to the
      chlamydial effector CPAF acting as an anaphase promoting complex mimic causing
      cells to exit mitosis with unaligned and unattached chromosomes. These lagging
      and missegregated chromosomes inhibit cytokinesis by blocking abscission, the
      final stage of cytokinesis.

PMID- 22646505
TI  - Can agricultural cultivation methods influence the healthfulness of crops for
      foods?
AB  - The aim of the current study was to investigate if there are any health effects
      of long-term consumption of organically grown crops using a rat model. Crops were
      retrieved over two years from a long-term field trial at three different
      locations in Denmark, using three different cultivation systems (OA, organic
      based on livestock manure; OB, organic based on green manure; and C, conventional
      with mineral fertilizers and pesticides) with two field replicates. The
      cultivation system had an impact on the nutritional quality, affecting gamma
      tocopherol, some amino acids, and fatty acid composition. Additionally, the
      nutritional quality was affected by harvest year and location. However, harvest
      year and location rather than cultivation system affected the measured health
      biomarkers. In conclusion, the differences in dietary treatments composed of
      ingredients from different cultivation systems did not lead to significant
      differences in the measured health biomarkers, except for a significant
      difference in plasma IgG levels.

PMID- 22646506
TI  - Protein phosphatase 1 is involved in IL-2-induced IL-5 and IL-13 expression in
      human T cells.
AB  - IL-2 plays an important role in immunological and other biological functions.
      This cytokine directly induces the production of several cytokines, such as IL-5
      and IL-13. The mechanisms of IL-2-mediated cytokine synthesis are mostly unclear;
      however, the involvement of IL-2 receptor (IL-2R)beta has been suggested. In this
      study, the signaling molecule downstream of IL-2Rbeta was investigated, employing
      a proteomic approach. Full-length IL-2Rbeta and its mutant in which the
      intracellular component was truncated were introduced in an IL-2Ralpha- and IL
      2Rgamma-stably transfected T cell hybridoma, S1. The differential phosphorylation
      profiles of protein tyrosine residues in these cells upon IL-2 stimulation were
      examined by two-dimensional gel electrophoresis. The candidate phosphoproteins of
      interest were re-covered, in-gel digested and mass spectrometry fingerprinted.
      Among proteins specifically phosphorylated in full-length IL-2Rbeta-expressing
      cells in response to IL-2 stimulation, protein phosphatase (PP)1beta and FK506
      binding protein 4 were identified. Particularly, PP1beta augmented IL-5 and IL-13
      expression stimulated by IL-2 but not by anti-CD3 antibody in human peripheral
      CD4+ T cells upon ectopic expression. IL-2-induced cytokine expression was
      suppressed by overexpression of PP1 regulatory subunit 2. A PP1 inhibitor,
      tautomycin, but not a PP2A inhibitor, okadaic acid, also inhibited the IL-2R
      mediated responses. It was conclusively shown that PP1 is crucially involved in
      IL-2-mediated IL-5 and IL-13 synthesis in human T cells.

PMID- 22646507
TI  - Pharmacogenomic biomarkers in dermatologic drugs.
AB  - Biomarkers are becoming increasingly important when considering the efficacy,
      toxicology, mechanism of action, and risk of adverse events in certain drugs. As
      availability of bio-genomic information increases, more treatments can be
      tailored to specific individuals, with a net effect of improved health outcomes.
      Many dermatology drugs have pharmacogenomic information on their labels. Knowing
      the risks and benefits associated with genomic biomarkers can aid physicians to
      make more knowledgeable decisions when identifying treatments for their patients.

PMID- 22646508
TI  - Pathological complete response and accelerated drug approval in early breast
      cancer.

PMID- 22646509
TI  - Medication reconciliation for controlled substances--an "ideal" prescription-drug
      monitoring program.

PMID- 22646510
TI  - Two hundred years of cancer research.

PMID- 22646511
TI  - Residents' response to duty-hour regulations--a follow-up national survey.

PMID- 22646512
TI  - Rationale and design of a multicenter prospective cohort study for the eVALuation
      and monitoring of HPV infections and relATEd cervical diseases in high-risk women
      (VALHIDATE study).
AB  - BACKGROUND: Pap screening, an effective method for cervical cancer prevention, is
      now supported by molecular human papillomavirus (HPV) testing. Recently
      commercialised preventive vaccines also provide new tools for the primary
      prevention of cervical cancer. To determine appropriate prevention strategies,
      the Health General Direction, Lombardy Region, funded a project that aims to
      characterize and monitor HPV infections and related cervical diseases in high
      risk women. METHODS/DESIGN: VALHIDATE is a 5-year multicentre open prospective
      cohort study. It will recruit 7000 consenting women aged 13-65 years to provide
      information about the local biomolecular epidemiology of HPV infection and
      cervical diseases in high-risk women recruited from nine clinical centres and one
      faith-based organisation. The study will estimate the overall and type-specific
      prevalence of HPV infection and cervical abnormalities. It also aims to compare
      standard Pap screening with biomolecular screening, and to assist in the design
      of targeted regional prevention programs directed specifically at high-risk
      groups. Three groups of high-risk women: 1000 HIV-infected women (aged 26-65
      years), 1000 recent migrant women (aged 26-65 years) and 3000 young women (aged
      13-26 years) and 1 control group: 2000 women (aged 26-45 years) attending a
      spontaneous screening program, will be recruited. Sample sizes will be revised
      after the first year. Adult participants will undergo conventional cervical
      cytology, HPV DNA screening and genotyping. Paediatric participants will undergo
      HPV DNA testing and genotyping of urine samples. HPV DNA, cytological
      abnormalities and HPV types will be analysed according to demographic,
      epidemiological, behavioural, and clinical data collected in an electronic case
      report form. Overall and stratified prevalences will be estimated to analyse the
      associations between HPV infection and selected characteristics. Logistic
      regression models will be used to estimate crude and adjusted odds ratios. Cox
      proportional hazard models will be used to estimate hazard ratios over time and
      between groups. DISCUSSION/MAIN EXPECTED RESULTS: This study will provide
      substantial insight into HPV infections and related cervical diseases in high
      risk groups and will help determine appropriate regional cervical cancer
      prevention strategies.

PMID- 22646513
TI  - Structure and electronic transport in graphene wrinkles.
AB  - Wrinkling is a ubiquitous phenomenon in two-dimensional membranes. In particular,
      in the large-scale growth of graphene on metallic substrates, high densities of
      wrinkles are commonly observed. Despite their prevalence and potential impact on
      large-scale graphene electronics, relatively little is known about their
      structural morphology and electronic properties. Surveying the graphene landscape
      using atomic force microscopy, we found that wrinkles reach a certain maximum
      height before folding over. Calculations of the energetics explain the
      morphological transition and indicate that the tall ripples are collapsed into
      narrow standing wrinkles by van der Waals forces, analogous to large-diameter
      nanotubes. Quantum transport calculations show that conductance through these
      "collapsed wrinkle" structures is limited mainly by a density-of-states
      bottleneck and by interlayer tunneling across the collapsed bilayer region. Also
      through systematic measurements across large numbers of devices with wide "folded
      wrinkles", we find a distinct anisotropy in their electrical resistivity,
      consistent with our transport simulations. These results highlight the coupling
      between morphology and electronic properties, which has important practical
      implications for large-scale high-speed graphene electronics.

PMID- 22646514
TI  - Effect of temporal predictability on the neural processing of self-triggered
      auditory stimulation during vocalization.
AB  - BACKGROUND: Sensory consequences of our own actions are perceived differently
      from the sensory stimuli that are generated externally. The present event-related
      potential (ERP) study examined the neural responses to self-triggered stimulation
      relative to externally-triggered stimulation as a function of delays between the
      motor act and the stimulus onset. While sustaining a vowel phonation, subjects
      clicked a mouse and heard pitch-shift stimuli (PSS) in voice auditory feedback at
      delays of either 0 ms (predictable) or 500-1000 ms (unpredictable). The motor
      effect resulting from the mouse click was corrected in the data analyses. For the
      externally-triggered condition, PSS were delivered by a computer with a delay of
      500-1000 ms after the vocal onset. RESULTS: As compared to unpredictable
      externally-triggered PSS, P2 responses to predictable self-triggered PSS were
      significantly suppressed, whereas an enhancement effect for P2 responses was
      observed when the timing of self-triggered PSS was unpredictable. CONCLUSIONS:
      These findings demonstrate the effect of the temporal predictability of stimulus
      delivery with respect to the motor act on the neural responses to self-triggered
      stimulation. Responses to self-triggered stimulation were suppressed or enhanced
      compared with the externally-triggered stimulation when the timing of stimulus
      delivery was predictable or unpredictable. Enhancement effect of unpredictable
      self-triggered stimulation in the present study supports the idea that sensory
      suppression of self-produced action may be primarily caused by an accurate
      prediction of stimulus timing, rather than a movement-related non-specific
      suppression.

PMID- 22646515
TI  - Multiple lessons from the multiple functions of a regulator of type III secretion
      system assembly in the plant pathogen Pseudomonas syringae.
AB  - The assembly of type III secretion systems (T3SSs), which inject bacterial
      effector proteins into the cytosol of animal and plant hosts, is a highly
      regulated process. Animal pathogens use a length-control protein to produce T3SS
      needles of fixed length and then a second regulator, such as YopN in Yersinia
      spp, to mediate host contact-dependent effector delivery. For Pseudomonas
      syringae and other plant pathogens, regulation of the assembly process differs
      because the T3SS pilus must grow through variably thick plant cell walls before
      contacting the host plasma membrane. In this issue of Molecular Microbiology,
      Crabill et al. (2012) report evidence that the YopN homologue HrpJ is a
      multifunctional regulator of T3SS assembly in DC3000. A hrpJ mutant hyper
      secretes pilus protein and no longer secretes four translocator proteins in
      culture, and it fails to inject effectors in planta. As with other proteins in
      this class, HrpJ is itself a T3SS substrate, but secretion-incompetent forms
      retain regulatory function. However, HrpJ is unusual in suppressing innate immune
      responses within host cells, as demonstrated with transgenic plants. The multiple
      capabilities of HrpJ appear to couple host contact sensing with pilus length
      control and translocator secretion while also contributing to immunity
      suppression early in the interaction.

PMID- 22646516
TI  - Pharmacological comparison of novel synthetic fenamate analogues with econazole
      and 2-APB on the inhibition of TRPM2 channels.
AB  - BACKGROUND AND PURPOSE: Fenamate analogues, econazole and 2-aminoethoxydiphenyl
      borate (2-APB) are inhibitors of transient receptor potential melastatin 2
      (TRPM2) channels and are used as research tools. However, these compounds have
      different chemical structures and therapeutic applications. Here we have
      investigated the pharmacological profile of TRPM2 channels by application of
      newly synthesized fenamate analogues and the existing channel blockers.
      EXPERIMENTAL APPROACH: Human TRPM2 channels in tetracycline-regulated pcDNA4/TO
      vectors were transfected into HEK293 T-REx cells and the expression was induced
      by tetracycline. Whole cell currents were recorded by patch-clamp techniques.
      Ca(2+) influx or release was monitored by fluorometry. KEY RESULTS: Flufenamic
      acid (FFA), mefenamic acid (MFA) and niflumic acid (NFA) concentration
      dependently inhibited TRPM2 current with potency order FFA > MFA = NFA.
      Modification of the 2-phenylamino ring by substitution of the trifluoromethyl
      group in FFA with -CH(3), -F, -CF(3), -OCH(3), -OCH(2)CH(3), -COOH, and -NO(2) at
      various positions, reduced channel blocking potency. The conservative
      substitution of 3-CF(3) in FFA by -CH(3) (3-MFA), however, gave the most potent
      fenamate analogue with an IC(50) of 76 uM, comparable to that of FFA, but unlike
      FFA, had no effect on Ca(2+) release. 3-MFA and FFA inhibited the channel
      intracellularly. Econazole and 2-APB showed non-selectivity by altering cytosolic
      Ca(2+) movement. Econazole also evoked a non-selective current. CONCLUSION AND
      IMPLICATIONS: The fenamate analogue 3-MFA was more selective than other TRPM2
      channel blockers. FFA, 2-APB and econazole should be used with caution as TRPM2
      channel blockers, as these compounds can interfere with intracellular Ca(2+)
      movement.

PMID- 22646517
TI  - Suicidal ideation, depression, and conduct disorder in a sample of adolescent and
      young adult twins.
AB  - The co-occurrence of suicidal ideation, depression, and conduct disturbance is
      likely explained in part by correlated genetic and environmental risk factors.
      Little is known about the specific nature of these associations. Structured
      interviews on 2,814 twins from the Virginia Twin Study of Adolescent Behavioral
      Development (VTSABD) and Young Adult Follow-Up (YAFU) yielded data on symptoms of
      depression, conduct disorder, and adolescent and young adult suicidal ideation.
      Univariate analyses revealed that the familial aggregation for each trait was
      explained by a combination of additive genetic and shared environmental effects.
      Suicidal ideation in adolescence was explained in part by genetic influences, but
      predominantly accounted for by environmental factors. A mixture of genetic and
      shared environmental influences explained ideation occurring in young adulthood.
      Multivariate analyses revealed that there are genetic and shared environmental
      effects common to suicidal ideation, depression, and conduct disorder. The
      association between adolescent suicidal ideation and CD was attributable to the
      same genetic and environmental risk factors for depression. These findings
      underscore that prevention and intervention strategies should reflect the
      different underlying mechanisms involving depression and conduct disorder to
      assist in identifying adolescents at suicidal risk.

PMID- 22646518
TI  - Design and fabrication of a biodegradable, covalently crosslinked shape-memory
      alginate scaffold for cell and growth factor delivery.
AB  - The successful use of transplanted cells and/or growth factors for tissue repair
      is limited by a significant cell loss and/or rapid growth factor diffusion soon
      after implantation. Highly porous alginate scaffolds formed with covalent
      crosslinking have been used to improve cell survival and growth factor release
      kinetics, but require open-wound surgical procedures for insertion and have not
      previously been designed to readily degrade in vivo. In this study, a
      biodegradable, partially crosslinked alginate scaffold with shape-memory
      properties was fabricated for minimally invasive surgical applications. A mixture
      of high and low molecular weight partially oxidized alginate modified with RGD
      peptides was covalently crosslinked using carbodiimide chemistry. The scaffold
      was compressible 11-fold and returned to its original shape when rehydrated.
      Scaffold degradation properties in vitro indicated ~85% mass loss by 28 days. The
      greater than 90% porous scaffolds released the recombinant growth factor insulin
      like growth factor-1 over several days in vitro and allowed skeletal muscle cell
      survival, proliferation, and migration from the scaffold over a 28-day period.
      The compressible scaffold thus has the potential to be delivered by a minimally
      invasive technique, and when rehydrated in vivo with cells and/or growth factors,
      could serve as a temporary delivery vehicle for tissue repair.

PMID- 22646519
TI  - Demographic and economic predictors of mental health problems and contact with
      treatment resources among adults in a low-income primary care setting.
AB  - The purpose of this study was to examine the prevalence of mental health-related
      problems in a low-income primary care setting, as well as the demographic and
      economic variables associated with these problems and contact with treatment
      resources. A total of 346 patient records were randomly selected among patients
      at an urban Iowa primary care clinic serving lower-income and uninsured
      individuals. Logistic models examined relationships among demographic factors,
      poverty level, and insurance status and three outcomes: Lifetime mental health
      problems, receipt of pharmacological intervention, and contact with psychosocial
      services. Female gender was associated with reporting mental health problems, and
      age and ethnicity interacted to predict reported mental health problems. Among
      those reporting mental health problems, female gender was predictive of contact
      with psychosocial services, while female gender with Caucasian ethnicity was
      predictive of receiving pharmacological intervention. Results support the need
      for primary care providers working with lower-income individuals to be active in
      discussing mental health issues with patients.

PMID- 22646520
TI  - Recalling semantic information about newly learned faces and voices.
AB  - Several findings showed that semantic information is more likely to be retrieved
      from recognised faces than from recognised voices. Earlier experiments, which
      investigated the recall of biographical information following person recognition,
      used stimuli that were pre-experimentally familiar to the participants, such as
      famous people's voices and faces. We propose an alternative method to compare the
      participants' ability to associate semantic information with faces and voices.
      The present experiments allowed a very strict control of frequency of exposure to
      pre-experimentally unfamiliar faces and voices and ensured the absence of
      identity clues in the spoken extracts. In Experiment 1 semantic information was
      retrieved from the presentation of a name. In Experiment 2 semantic and lexical
      information was retrieved from faces and/or voices. A memory advantage for faces
      over voices was again observed.

PMID- 22646521
TI  - Changes to the financial responsibility for juvenile court ordered psychiatric
      evaluations reduce inpatient services utilization: an interrupted time series
      study.
AB  - BACKGROUND: The purpose of the current study was to evaluate the impact of a July
      2008 Tennessee Court of Appeals opinion that shifted financial responsibility for
      juvenile court ordered psychiatric evaluations from the State to the County.
      METHODS: We used de-identified administrative data from the Tennessee Department
      of Mental Health and mid-year population estimates from the U.S. Census Bureau
      from July 1, 2006 to June 30, 2010, and an interrupted time series design with
      segmented regression analysis to quantify the impact of the implementation of the
      Court opinion. RESULTS: In the study period, there were 2,176 referrals for
      juvenile court ordered psychiatric evaluations in Tennessee; of these, 74.1% were
      inpatient evaluations. The Court opinion was associated with a decrease of 9.4
      (95% C.I. = 7.9-10.8) inpatient and increase of 1.2 (95% C.I. = 0.4-2.1)
      outpatient evaluations per 100,000 Tennessee youth aged 12 to 19 years per month.
      CONCLUSIONS: The Court opinion that shifted financial responsibility for juvenile
      court ordered psychiatric evaluations from the State to the County was associated
      with a sudden and significant decrease in inpatient psychiatric evaluations, and
      more modest increase in outpatient evaluations.

PMID- 22646522
TI  - Comparison of Atlantic salmon individuals with different outcomes of
      cardiomyopathy syndrome (CMS).
AB  - BACKGROUND: Cardiomyopathy syndrome (CMS) is a severe disease of Atlantic salmon
      (Salmo salar L.) associated with significant economic losses in the aquaculture
      industry. CMS is diagnosed with a severe inflammation and degradation of
      myocardial tissue caused by a double-stranded RNA virus named piscine myocarditis
      virus (PMCV), with structural similarities to the Totiviridae family. In the
      present study we characterized individual host responses and genomic determinants
      of different disease outcomes. RESULTS: From time course studies of
      experimentally infected Atlantic salmon post-smolts, fish exhibited different
      outcomes of infection and disease. High responder (HR) fish were characterized
      with sustained and increased viral load and pathology in heart tissue. Low
      responder (LR) fish showed declining viral load from 6-10 weeks post infection
      (wpi) and absence of pathology. Global gene expression (SIQ2.0 oligonucleotide
      microarray) in HR and LR hearts during infection was compared, in order to
      characterize differences in the host response and to identify genes with
      expression patterns that could explain or predict the different outcomes of
      disease. Virus-responsive genes involved in early antiviral and innate immune
      responses were upregulated equally in LR and HR at the first stage (2-4 wpi),
      reflecting the initial increase in virus replication. Repression of heart muscle
      development was identified by gene ontology enrichment analyses, indicating the
      early onset of pathology. By six weeks both responder groups had comparable viral
      load, while increased pathology was observed in HR fish. This was reflected by
      induced expression of genes implicated in apoptosis and cell death mechanisms,
      presumably related to lymphocyte regulation and survival. In contrast, LR fish
      showed earlier activation of NK cell-mediated cytotoxicity and NOD-like receptor
      signaling pathways. At the late stage of infection, increased pathology and viral
      load in HR was accompanied by a broad activation of genes involved in adaptive
      immunity and particularly T cell responses, probably reflecting the increased
      infiltration and homing of virus-specific T cells to the infected heart. This was
      in sharp contrast to LR fish, where recovery and reduced viral load was
      associated with a significantly reduced transcription of adaptive immunity genes
      and activation of genes involved in energy metabolism. CONCLUSIONS: In contrast
      to LR, a stronger and sustained expression of genes involved in adaptive immune
      responses in heart tissue of HR at the late stage of disease probably reflected
      the increased lymphocyte infiltration and pathological outcome. In addition to
      controlled adaptive immunity and activation of genes involved in cardiac energy
      metabolism in LR at the late stage, recovery of this group could also be related
      to an earlier activation of NOD-like receptor signaling and NK cell-mediated
      cytotoxicity pathways.

PMID- 22646523
TI  - Flowering dynamics and pollination system of the sedge Rhynchospora ciliata
      (Vahl) Kukenth (Cyperaceae): does ambophily enhance its reproductive success?
AB  - Cyperaceae are characteristically anemophilous, but there are some reports of
      species re-adapted to entomophily, such as Rhynchospora ciliata. Our objective
      was to investigate: (1) the distribution pattern of flowers in inflorescences of
      Rhynchospora ciliata; (2) the dynamics of its anthesis; and (3) whether R.
      ciliata is pollinated by bees, by wind or by both. Additionally, we tested the
      hypotheses: (i) the hypsophylls and/or anthers attract pollinators, and (ii)
      biotic vectors enhance the reproductive success of R. ciliata. We analysed floral
      biology, dynamics of anthesis, frequency and behaviour of insects visiting
      flowers; we also carried out experiments on flower attractiveness, pollination by
      wind and reproductive success. Rhynchospora ciliata has flowers with anemophilous
      attributes, including anthers exposed during anthesis; however, the anthers (here
      considered a mixed trait) together with the white hypsophylls can be considered
      as attributes that favour entomophily. Both wind and four species of bee were
      considered as pollen vectors of R. ciliata. Through flower attractiveness tests,
      we observed that the hypsophylls do not affect the frequency of pollinating bees
      and that the absence of exposed anthers affects the average number of visits,
      probably because pollen is the only floral resource. Reproductive tests indicate
      that R. ciliata is self-incompatible and that ambophily enhances its reproductive
      success.

PMID- 22646524
TI  - Talking about alcohol consumption: health campaigns, conversational valence, and
      binge drinking intentions.
AB  - OBJECTIVES: Although research has shown that whether people talk about health
      issues influences health campaign effects, no evidence exists on whether
      conversational valence fulfils a mediating role within health campaign effects.
      In the context of alcohol consumption, this two-wave experimental research
      studies the effects of exposure to an anti-alcohol message on conversational
      valence about alcohol. Further, it investigates whether valence subsequently
      affects alcohol consumption intentions. DESIGN: Eighty-four undergraduate
      students, in dyads, were randomly assigned to one of two conditions (anti-alcohol
      message vs. no alcohol message exposure). METHODS: A baseline measure of the
      intention to refrain from binge drinking was assessed in advance. Two weeks
      later, half of the participants were exposed to an anti-alcohol message, after
      which all pairs engaged in a conversation about alcohol and binge drinking
      followed by an assessment of conversational valence and again the intention to
      refrain from binge drinking. RESULTS: An indirect effect of health message
      exposure on the intention to refrain from binge drinking through conversational
      valence was revealed. When participants viewed an anti-alcohol message, they
      reported significantly more negative conversations about alcohol. Subsequently, a
      more negative conversational valence about alcohol increased the intention to
      refrain from binge drinking. CONCLUSIONS: These findings suggest that
      conversational valence is relevant for health campaign effects. By demonstrating
      that health messages can influence this valence, important implications arise in
      terms of health promotion. Future research should focus on how to design
      effective health campaigns that are able to guide conversational valence in the
      desired direction.

PMID- 22646525
TI  - Habituation of rapid sympathetic response to aversive timbre eliminated by change
      in basal sympathovagal balance.
AB  - We studied the difference in the habituation of the rapid sympathetic response to
      slightly and highly aversive timbres in 68 males. We measured the decrease in the
      blood volume pulse amplitude (BVP response) as the rapid sympathetic response and
      the low- (0.04-0.15 Hz) to high- (0.15-0.40 Hz) frequency (LF/HF) ratio of heart
      rate variability as the sympathovagal balance. The BVP response was suppressed
      for slightly aversive timbres that had been presented once before, but not for a
      highly aversive timbre. In contrast, the prior presentation of a highly aversive
      timbre enhanced the BVP response to a slightly aversive timbre. Only a highly
      aversive timbre reduced the LF/HF ratio. We suggest that the lack of habituation
      of the rapid sympathetic response to an aversive timbre is the result of the
      balance between the effects of the increase caused by the change in sympathovagal
      balance to vagal dominance and the decrease caused by classical habituation.

PMID- 22646526
TI  - New developments in the treatment of osteoporosis.
AB  - The last 25 years have seen the development of a plethora of new, effective
      agents for the treatment of osteoporosis. These agents reduce the risk of spine
      fractures by up to 70%, hip fractures by 40-50% and non-vertebral fractures by up
      to 50-80%. Amino-bisphosphonates, taken orally or intravenously, remain the
      dominant treatment modalities for osteoporosis. These so-called anti-resorptive
      or anti-catabolic agents stabilize the skeleton and reduce fracture risk in
      osteoporotic as well as osteopenic individuals. A monoclonal antibody against
      receptor activator of nuclear factor kappaB ligand, Denosumab, constitutes a new
      anti-resorptive agent recently approved worldwide. In younger postmenopausal
      women, low-dose estrogen or estrogen/progestin still has a place for short-term
      (up to 5 years) preservation of bone mass, especially in women with menopausal
      symptoms. Likewise, selective estrogen receptor modulators should be considered
      in younger postmenopausal women, especially those at increased risk of breast
      cancer. Anabolic (bone forming) regimens, of which parathyroid hormone is the
      only agent currently available, aid in the build up of new bone, increase bone
      mass and improve bone architecture. In cancellous bone, 30-60% increases of bone
      mass have been documented, but cortical bone thickness also increases. These
      improvements lead to profound reduction in fracture rates in both the axial and
      appendicular skeleton. Owing to cost and the need for parenteral administration,
      in most countries these agents are reserved for severe osteoporosis with multiple
      fractures.

PMID- 22646527
TI  - Efficacy and safety of sclerotherapy for digital mucous cysts.
AB  - BACKGROUND: Digital mucous cysts (DMCs) are common tumor of the adjacent distal
      interphalangeal joint that causes leakage of mucinous material from the joint.
      There are various treatment modalities for DMCs, among which sclerotherapy has
      been reported as an effective alternative treatment. OBJECTIVES: To evaluate the
      safety and efficacy of sclerotherapy for DMC. PATIENTS AND METHODS: We
      retrospectively reviewed 12 patients with DMC treated with sclerotherapy. 0.5%
      Sodium tetradecyl sulfate 0.2-0.3 cc was injected into the pseudocystic lesions
      after the complete evacuation of mucinous material. RESULTS: Eleven of 12 lesions
      regressed successfully, including four lesions that resolved after a single
      treatment. The mean number of treatments was 2.4. The mean follow-up period was
      18.3 months after the last treatment. There was one case of recurrence after the
      last treatment. Complications such as mild edema, inflammation and pain were
      noted in three patients, which resolved within few days. CONCLUSIONS: According
      to the results of the present study, sclerotherapy is a feasible alternative
      treatment modality for DMCs. Treatment was well tolerated with few side effects,
      and resulted in high cure rate. Due to its less invasive nature, high
      accessibility and favorable outcomes, sclerotherapy should be considered a
      satisfactory option for the treatment of DMC.

PMID- 22646528
TI  - Capability of Lactobacillus plantarum IFPL935 to catabolize flavan-3-ol compounds
      and complex phenolic extracts.
AB  - Lactobacillus plantarum IFPL935 was incubated with individual monomeric flavan-3
      ols and dimeric A- and B-type procyanidins to identify new metabolites and to
      determine the effect of compound structural features on bacterial growth and
      catabolism. Complex extracts rich in A-type proanthocyanidins and phenolic acids
      from cranberry were also tested. The results showed that L. plantarum IFPL935
      exhibited higher resistance to nongalloylated monomeric flavan-3-ols, A-type
      dimeric procyanidins, and cranberry extract than to (-)-epicatechin-3-O-gallate
      and B-type dimeric procyanidins. Despite these findings, the strain was capable
      of rapidly degrading (-)-epicatechin-3-O-gallate, but not A- or B-type dimeric
      procyanidins. However, it was able to produce large changes in the phenolic
      profile of the cranberry extract mainly due to the catabolism of hydroxycinnamic
      and hydroxybenzoic acids. Of most relevance was the fact that L. plantarum
      IFPL935 cleaved the heterocyclic ring of monomeric flavan-3-ols, giving rise to 1
      (3',4'-dihydroxyphenyl)-3-(2",4",6"-trihydroxyphenyl)propan-2-ol, activity
      exhibited by only a few human intestinal bacteria.

PMID- 22646529
TI  - Synthesis of indolines, indoles, and benzopyrrolizidinones from simple aryl
      azides.
AB  - A simple approach to prepare indolines and benzopyrrolizidinones from ortho
      azidoallylbenzenes via a tandem radical addition/cyclization is described. The
      use of triethylborane to initiate and sustain the process provides the best
      results. Indolines are easily converted into the corresponding indoles by
      oxidation with manganese dioxide.

PMID- 22646530
TI  - Genetic assessment of population structure and connectivity in the threatened
      Mediterranean coral Astroides calycularis (Scleractinia, Dendrophylliidae) at
      different spatial scales.
AB  - Understanding dispersal patterns, population structure and connectivity among
      populations is helpful in the management and conservation of threatened species.
      Molecular markers are useful tools as indirect estimators of these
      characteristics. In this study, we assess the population genetic structure of the
      orange coral Astroides calycularis in the Alboran Sea at local and regional
      scale, and at three localities outside of this basin. Bayesian clustering
      methods, traditional F-statistics and D(est) statistics were used to determine
      the patterns of genetic structure. Likelihood and coalescence approaches were
      used to infer migration patterns and effective population sizes. The results
      obtained reveal a high level of connectivity among localities separated by as
      much as 1 km and moderate levels of genetic differentiation among more distant
      localities, somewhat corresponding with a stepping-stone model of gene flow and
      connectivity. These data suggest that connectivity among populations of this
      coral is mainly driven by the biology of the species, with low dispersal
      abilities; in addition, hydrodynamic processes, oceanographic fronts and the
      distribution of rocky substrate along the coastline may influence larval
      dispersal.

PMID- 22646531
TI  - Mean platelet volume in Korean patients with hepatic diseases.

PMID- 22646532
TI  - Combining GLP-1 receptor agonists with insulin: therapeutic rationales and
      clinical findings.
AB  - Due to the increasing prevalence of type 2 diabetes mellitus (T2DM), the emergent
      trend towards diagnosis in younger patients and the progressive nature of this
      disease, many more patients than before now require insulin to maintain glycaemic
      control. However, there is a degree of inertia among physicians and patients
      regarding the initiation and intensification of insulin therapy, in part due to
      concerns about the associated weight gain and increased risk of hypoglycaemia.
      Glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase insulin release and
      suppress glucagon secretion in a glucose-dependent manner, thus conferring
      glycaemic control with a low incidence of hypoglycaemia. GLP-1RAs also promote
      weight loss, and have beneficial effects on markers of beta cell function, lipid
      levels, blood pressure and cardiovascular risk markers. However, the durability
      of their effectiveness is unknown and, compared with insulin, the
      antihyperglycaemic efficacy of GLP-1RAs is limited. The combination of a GLP-1RA
      and insulin might thus be highly effective for optimal glucose control,
      ameliorating the adverse effects typically associated with insulin. Data from
      clinical studies support the therapeutic potential of GLP-1RA-insulin combination
      therapy, typically showing beneficial effects on glycaemic control and body
      weight, with a low incidence of hypoglycaemia and, in established insulin
      therapy, facilitating reductions in insulin dose. In this review, the
      physiological and pharmacological rationale for using GLP-1RA and insulin
      therapies in combination is discussed, and data from clinical studies that have
      assessed the efficacy and safety of this treatment strategy are outlined.

PMID- 22646535
TI  - Strategic design and recent fabrication techniques for bioengineered tissue
      scaffolds to improve peripheral nerve regeneration.
AB  - Bioengineered tissue scaffolds are a potential tool for improving regenerative
      repair of damaged peripheral nerves. Novel modes of fabrication coupled with
      scaffold design strategies that are based on an understanding of the biology of
      nerve injury offer the prospect of intervention at a more sophisticated level. We
      review the etiology and incidence of peripheral nerve injury and the biological
      events that unfold during nerve regeneration after an injury. Newly available
      tissue scaffold fabrication technologies using bioplotting and laser-based
      techniques are described. Scaffold design strategies are also discussed,
      including the incorporation of living cells during scaffold fabrication,
      inclusion of neurotrophic gradients, use of electric stimulation, inclusion of
      antioxidant compounds to counteract neural apotosis, and promotion of
      angiogenesis. Use of these advanced fabrication techniques and incorporation of
      one or more of these active biological strategies may eventually lead to a
      greater success in peripheral nerve tissue engineering.

PMID- 22646534
TI  - Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer
      invasion.
AB  - BACKGROUND: Membrane-anchored heparin-binding epidermal growth factor-like growth
      factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor
      receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF)
      after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed
      proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate
      from the plasma membrane to the nucleus and regulate cell cycle after shedding
      stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric
      cancer is unclear. METHODS: We investigated the relationship between
      intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer
      patients treated with gastrectomy. Moreover, we established stable gastric cancer
      cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF
      mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility
      between these 2 gastric cancer cell lines was investigated using a transwell
      invasion assay and a wound healing assay. RESULTS: Of the 96 gastric cancer
      cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm
      in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear
      immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors
      compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P < 0.01). The
      growth of wt-HB-EGF- and HB-EGF-mC-expressing cells significantly increased
      compared with control cells, but the growth of HB-EGF-mC-expressing cells was
      significantly decreased compared with wt-HB-EGF-expressing cells. Gastric cancer
      cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in
      HB-EGF-mC-expressing cells showed a slight increase compared with control cells.
      Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing,
      but had no significant effect in HB-EGF-mC-expressing cells. CONCLUSIONS: Both
      the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear
      translocation induce gastric cancer growth, whereas HB-EGF-C nuclear
      translocation independently plays a critical role in gastric cancer invasion. The
      present study demonstrated that HB-EGF-C nuclear translocation might be crucial
      in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic
      marker and a new molecular target for gastric cancer therapy.

PMID- 22646533
TI  - The antinociceptive triterpene beta-amyrin inhibits 2-arachidonoylglycerol (2-AG)
      hydrolysis without directly targeting cannabinoid receptors.
AB  - BACKGROUND AND PURPOSE: Pharmacological activation of cannabinoid CB(1) and CB(2)
      receptors is a therapeutic strategy to treat chronic and inflammatory pain. It
      was recently reported that a mixture of natural triterpenes alpha- and beta
      amyrin bound selectively to CB(1) receptors with a subnanomolar K(i) value (133
      pM). Orally administered alpha/beta-amyrin inhibited inflammatory and persistent
      neuropathic pain in mice through both CB(1) and CB(2) receptors. Here, we
      investigated effects of amyrins on the major components of the endocannabinoid
      system. EXPERIMENTAL APPROACH: We measured CB receptor binding interactions of
      alpha- and beta-amyrin in validated binding assays using hCB(1) and hCB(2)
      transfected CHO-K1 cells. Effects on endocannabinoid transport in U937 cells and
      breakdown using homogenates of BV2 cells and pig brain, as well as purified
      enzymes, were also studied. KEY RESULTS: There was no binding of either alpha- or
      beta-amyrin to hCB receptors in our assays (K(i) > 10 uM). The triterpene beta
      amyrin potently inhibited 2-arachidonoyl glycerol (2-AG) hydrolysis in pig brain
      homogenates, but not that of anandamide. Although beta-amyrin only weakly
      inhibited purified human monoacylglycerol lipase (MAGL), it also inhibited
      alpha,beta-hydrolases and more potently inhibited 2-AG breakdown than alpha
      amyrin and the MAGL inhibitor pristimerin in BV2 cell and pig brain homogenates.
      CONCLUSIONS AND IMPLICATIONS: We propose that beta-amyrin exerts its analgesic
      and anti-inflammatory pharmacological effects via indirect cannabimimetic
      mechanisms by inhibiting the degradation of the endocannabinoid 2-AG without
      interacting directly with CB receptors. Triterpenoids appear to offer a very
      broad and largely unexplored scaffold for inhibitors of the enzymic degradation
      of 2-AG. LINKED ARTICLES: This article is part of a themed section on
      Cannabinoids. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2012.167.issue-8.

PMID- 22646536
TI  - Drawing perseveration in neglect: effects of target density.
AB  - In cancellation tasks, patients with unilateral spatial neglect typically fail to
      mark targets within the side of the sheet contralateral to the side of the lesion
      (contralesional). Moreover, they can show a perseverative behaviour, which
      consists in repeatedly cancelling stimuli, mainly in the side of the display
      ipsilateral to the side of the lesion (ipsilesional). We investigated in 13 right
      brain-damaged patients with left spatial neglect and perseverative behaviour
      whether and how different densities of horizontal targets modulated omission and
      perseverative errors. We found that the density of targets modulated the
      patients' distribution of neglect (area of omission), but not its extent, as
      indexed by the percentage of omissions. Specifically, the area of omissions
      tightened when target density increased leftwards. On the other hand, target
      density did not affect the distribution of perseverative behaviour (area of
      perseveration), as well as its extent, as indexed by the percentage of
      perseverations. Correlation analyses showed that both the extent and the
      distribution of omissions were positively correlated to clinical measures of
      spatial neglect. Conversely, perseverations did not show such a correlation.
      These findings support the view that two different pathological mechanisms might
      be involved in left spatial neglect and in ipsilesional perseverative behaviour.

PMID- 22646628
TI  - Home: palliation for dying undocumented immigrants.

PMID- 22646629
TI  - Outbreak of salmonellosis linked to live poultry from a mail-order hatchery.
AB  - BACKGROUND: Outbreaks of human salmonella infections are increasingly associated
      with contact with live poultry, but effective control measures are elusive. In
      2005, a cluster of human salmonella Montevideo infections with a rare pattern on
      pulsed-field gel electrophoresis (the outbreak strain) was identified by
      PulseNet, a national subtyping network. METHODS: In cooperation with public
      health and animal health agencies, we conducted multistate investigations
      involving patient interviews, trace-back investigations, and environmental
      testing at a mail-order hatchery linked to the outbreak in order to identify the
      source of infections and prevent additional illnesses. A case was defined as an
      infection with the outbreak strain between 2004 and 2011. RESULTS: From 2004
      through 2011, we identified 316 cases in 43 states. The median age of the patient
      was 4 years. Interviews were completed with 156 patients (or their caretakers)
      (49%), and 36 of these patients (23%) were hospitalized. Among the 145 patients
      for whom information was available, 80 (55%) had bloody diarrhea. Information on
      contact with live young poultry was available for 159 patients, and 122 of these
      patients (77%) reported having such contact. A mail-order hatchery in the western
      United States was identified in 81% of the trace-back investigations, and the
      outbreak strain was isolated from samples collected at the hatchery. After
      interventions at the hatchery, the number of human infections declined, but
      transmission continued. CONCLUSIONS: We identified a prolonged multistate
      outbreak of salmonellosis, predominantly affecting young children and associated
      with contact with live young poultry from a mail-order hatchery. Interventions
      performed at the hatchery reduced, but did not eliminate, associated human
      infections, demonstrating the difficulty of eliminating salmonella transmission
      from live poultry.

PMID- 22646630
TI  - Preoperative chemoradiotherapy for esophageal or junctional cancer.
AB  - BACKGROUND: The role of neoadjuvant chemoradiotherapy in the treatment of
      patients with esophageal or esophagogastric-junction cancer is not well
      established. We compared chemoradiotherapy followed by surgery with surgery alone
      in this patient population. METHODS: We randomly assigned patients with
      resectable tumors to receive surgery alone or weekly administration of
      carboplatin (doses titrated to achieve an area under the curve of 2 mg per
      milliliter per minute) and paclitaxel (50 mg per square meter of body-surface
      area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days
      per week), followed by surgery. RESULTS: From March 2004 through December 2008,
      we enrolled 368 patients, 366 of whom were included in the analysis: 275 (75%)
      had adenocarcinoma, 84 (23%) had squamous-cell carcinoma, and 7 (2%) had large
      cell undifferentiated carcinoma. Of the 366 patients, 178 were randomly assigned
      to chemoradiotherapy followed by surgery, and 188 to surgery alone. The most
      common major hematologic toxic effects in the chemoradiotherapy-surgery group
      were leukopenia (6%) and neutropenia (2%); the most common major nonhematologic
      toxic effects were anorexia (5%) and fatigue (3%). Complete resection with no
      tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients
      in the chemoradiotherapy-surgery group versus 69% in the surgery group (P<0.001).
      A pathological complete response was achieved in 47 of 161 patients (29%) who
      underwent resection after chemoradiotherapy. Postoperative complications were
      similar in the two treatment groups, and in-hospital mortality was 4% in both.
      Median overall survival was 49.4 months in the chemoradiotherapy-surgery group
      versus 24.0 months in the surgery group. Overall survival was significantly
      better in the chemoradiotherapy-surgery group (hazard ratio, 0.657; 95%
      confidence interval, 0.495 to 0.871; P=0.003). CONCLUSIONS: Preoperative
      chemoradiotherapy improved survival among patients with potentially curable
      esophageal or esophagogastric-junction cancer. The regimen was associated with
      acceptable adverse-event rates. (Funded by the Dutch Cancer Foundation [KWF
      Kankerbestrijding]; Netherlands Trial Register number, NTR487.).

PMID- 22646632
TI  - Drowning.

PMID- 22646633
TI  - Images in clinical medicine. Splenic spirals.

PMID- 22646634
TI  - Case records of the Massachusetts General Hospital. Case 17-2012. A 54-year-old
      man with visual-field loss and a mass in the brain.

PMID- 22646631
TI  - Childhood outcomes after hypothermia for neonatal encephalopathy.
AB  - BACKGROUND: We previously reported early results of a randomized trial of whole
      body hypothermia for neonatal hypoxic-ischemic encephalopathy showing a
      significant reduction in the rate of death or moderate or severe disability at 18
      to 22 months of age. Long-term outcomes are now available. METHODS: In the
      original trial, we assigned infants with moderate or severe encephalopathy to
      usual care (the control group) or whole-body cooling to an esophageal temperature
      of 33.5 degrees C for 72 hours, followed by slow rewarming (the hypothermia
      group). We evaluated cognitive, attention and executive, and visuospatial
      function; neurologic outcomes; and physical and psychosocial health among
      participants at 6 to 7 years of age. The primary outcome of the present analyses
      was death or an IQ score below 70. RESULTS: Of the 208 trial participants,
      primary outcome data were available for 190. Of the 97 children in the
      hypothermia group and the 93 children in the control group, death or an IQ score
      below 70 occurred in 46 (47%) and 58 (62%), respectively (P=0.06); death occurred
      in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38
      (41%) and 53 (60%) (P=0.03). Other outcome data were available for the 122
      surviving children, 70 in the hypothermia group and 52 in the control group.
      Moderate or severe disability occurred in 24 of 69 children (35%) and 19 of 50
      children (38%), respectively (P=0.87). Attention-executive dysfunction occurred
      in 4% and 13%, respectively, of children receiving hypothermia and those
      receiving usual care (P=0.19), and visuospatial dysfunction occurred in 4% and 3%
      (P=0.80). CONCLUSIONS: The rate of the combined end point of death or an IQ score
      of less than 70 at 6 to 7 years of age was lower among children undergoing whole
      body hypothermia than among those undergoing usual care, but the differences were
      not significant. However, hypothermia resulted in lower death rates and did not
      increase rates of severe disability among survivors. (Funded by the National
      Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research
      Network; ClinicalTrials.gov number, NCT00005772.).

PMID- 22646635
TI  - The spread of neurodegenerative disease.

PMID- 22646637
TI  - Colorectal-cancer screening.

PMID- 22646638
TI  - Colorectal-cancer screening.

PMID- 22646639
TI  - Colorectal-cancer screening.

PMID- 22646640
TI  - Colorectal-cancer screening.

PMID- 22646642
TI  - Intratumor heterogeneity and branched evolution.

PMID- 22646643
TI  - Intratumor heterogeneity and branched evolution.

PMID- 22646644
TI  - Intratumor heterogeneity and branched evolution.

PMID- 22646646
TI  - Pasireotide in Cushing's disease.

PMID- 22646647
TI  - Pasireotide in Cushing's disease.

PMID- 22646648
TI  - The emerging threat of untreatable gonococcal infection.

PMID- 22646649
TI  - Lower-extremity lymphedema and elevated body-mass index.

PMID- 22646653
TI  - Images in clinical medicine. Palisaded neutrophilic and granulomatous dermatitis.

PMID- 22646654
TI  - The use of cephalosporins for gonorrhea: an update on the rising problem of
      resistance.
AB  - INTRODUCTION: Over the last several years, Neisseria gonorrhoeae has developed
      decreased susceptibility to extended-spectrum cephalosporins worldwide.
      Gonococcal antimicrobial surveillance programs in multiple regions have
      documented the rise in N. gonorrhoeae isolates' minimum inhibitory concentrations
      to cephalosporins, and the first cases of ceftriaxone treatment failure have been
      reported. These developments have prompted the use of the term 'superbug' and
      concerns about the emergence of untreatable gonococcal infections. AREAS COVERED:
      Since the publication of the last detailed review of the use of cephalosporins
      for gonorrhea in 2009, several new developments have occurred, which are detailed
      in this review. A variety of treatment strategies have been proposed in response
      to this 'superbug' threat, including increasing the dose or providing multiple
      doses of cephalosporins, multidrug therapy, rotating therapeutic regimens and
      individualized treatment based on susceptibility testing. EXPERT OPINION: A
      robust public health response is needed that includes better diagnosis and
      treatment of pharyngeal gonorrhea, improved surveillance of antimicrobial
      resistance, informed treatment approaches and reduction of the global burden of
      gonococcal infections.

PMID- 22646655
TI  - Historical habitat connectivity affects current genetic structure in a grassland
      species.
AB  - Many recent studies have explored the effects of present and past landscape
      structure on species distribution and diversity. However, we know little about
      the effects of past landscape structure on distribution of genetic diversity
      within and between populations of a single species. Here we describe the
      relationship between present and past landscape structure (landscape connectivity
      and habitat size estimated from historical maps) and current genetic structure in
      a perennial herb, Succisa pratensis. We used allozymes as co-dominant markers to
      estimate genetic diversity and deviation from Hardy-Weinberg equilibrium in 31
      populations distributed within a 5 km(2) agricultural landscape. The results
      showed that current genetic diversity of populations was related to habitat
      suitability, habitat age, habitat size and habitat connectivity in the past. The
      effects of habitat age and past connectivity on genetic diversity were in most
      cases also significant after taking the current landscape structure into account.
      Moreover, current genetic similarity between populations was affected by past
      connectivity after accounting for current landscape structure. In both cases, the
      oldest time layer (1850) was the most informative. Most populations showed
      heterozygote excess, indicating disequilibrium due to recent gene flow or
      selection against homozygotes. These results suggest that habitat age and past
      connectivity are important determinants of distribution of genetic diversity
      between populations at a scale of a few kilometres. Landscape history may
      significantly contribute to our understanding of distribution of current genetic
      structure within species and the genetic structure may be used to better
      understand landscape history, even at a small scale.

PMID- 22646657
TI  - Interpreting semantic clustering effects in free recall.
AB  - The order in which participants choose to recall words from a studied list of
      randomly selected words provides insights into how memories of the words are
      represented, organised, and retrieved. One pervasive finding is that when a pair
      of semantically related words (e.g., "cat" and "dog") is embedded in the studied
      list, the related words are often recalled successively. This tendency to
      successively recall semantically related words is termed semantic clustering
      (Bousfield, 1953; Bousfield & Sedgewick, 1944; Cofer, Bruce, & Reicher, 1966).
      Measuring semantic clustering effects requires making assumptions about which
      words participants consider to be similar in meaning. However, it is often
      difficult to gain insights into individual participants' internal semantic
      models, and for this reason researchers typically rely on standardised semantic
      similarity metrics. Here we use simulations to gain insights into the expected
      magnitudes of semantic clustering effects given systematic differences between
      participants' internal similarity models and the similarity metric used to
      quantify the degree of semantic clustering. Our results provide a number of
      useful insights into the interpretation of semantic clustering effects in free
      recall.

PMID- 22646656
TI  - Phage shock proteins B and C prevent lethal cytoplasmic membrane permeability in
      Yersinia enterocolitica.
AB  - The bacterial phage shock protein (Psp) stress response system is activated by
      events affecting the cytoplasmic membrane. In response, Psp protein levels
      increase, including PspA, which has been implicated as the master effector of
      stress tolerance. Yersinia enterocolitica and related bacteria with a defective
      Psp system are highly sensitive to the mislocalization of pore-forming secretin
      proteins. However, why secretins are toxic to psp null strains, whereas some
      other Psp inducers are not, has not been explained. Furthermore, previous work
      has led to the confounding and disputable suggestion that PspA is not involved in
      mitigating secretin toxicity. Here we have established a correlation between the
      amount of secretin toxicity in a psp null strain and the extent of cytoplasmic
      membrane permeability to large molecules. This leads to a morphological change
      resembling cells undergoing plasmolysis. Furthermore, using novel strains with
      dis-regulated Psp proteins has allowed us to obtain unequivocal evidence that
      PspA is not required for secretin-stress tolerance. Together, our data suggest
      that the mechanism by which secretin multimers kill psp null cells is by causing
      a profound defect in the cytoplasmic membrane permeability barrier. This allows
      lethal molecular exchange with the environment, which the PspB and PspC proteins
      can prevent.

PMID- 22646658
TI  - Limitations of the rhesus macaque draft genome assembly and annotation.
AB  - Finished genome sequences and assemblies are available for only a few
      vertebrates. Thus, investigators studying many species must rely on draft
      genomes. Using the rhesus macaque as an example, we document the effects of
      sequencing errors, gaps in sequence and misassemblies on one automated gene model
      pipeline, Gnomon. The combination of draft genome with automated gene finding
      software can result in spurious sequences. We estimate that approximately 50% of
      the rhesus gene models are missing, incomplete or incorrect. The problems
      identified in this work likely apply to all draft vertebrate genomes annotated
      with any automated gene model pipeline and thus represent a pervasive challenge
      to the analysis of draft genomes.

PMID- 22646659
TI  - An exploratory randomised controlled trial using short messaging service to
      facilitate insulin administration in young adults with type 1 diabetes.
AB  - This exploratory randomised controlled trial examined the effectiveness of a
      novel short messaging service intervention underpinned by the theory of planned
      behaviour (TPB) in improving insulin administration in young adults with type 1
      diabetes and the role of moderating variables. Those in the intervention
      condition (N = 8) received one daily text message underpinned by TPB constructs:
      Attitudes, subjective norms, perceived behavioural control and intention. Those
      in the control condition (N = 10) received weekly general health messages. Self
      reported insulin administration was the main outcome measure; conscientiousness
      and consideration of future consequences (CFC) were measured as potential
      moderators. Analyses of covariance revealed no main effects of condition for
      morning and afternoon injections but a marginally significant effect for evening
      injections (p = .08). This main effect was qualified by significant interactions
      of condition with conscientiousness (p = .001), CFC (p = .007) and a three-way
      interaction among condition, conscientiousness and CFC (p = .009). Exploration of
      the interactions indicated the intervention significantly improved evening
      injection rates only in the low conscientiousness and low CFC groups. This effect
      was particularly strong among those low in both conscientiousness and CFC.
      Further investigation is warranted, using more objective measures of insulin
      adherence in a larger sample.

PMID- 22646660
TI  - Steric restrictions of RISC in RNA interference identified with size-expanded RNA
      nucleobases.
AB  - Understanding the interactions between small interfering RNAs (siRNAs) and the
      RNA-induced silencing complex (RISC), the key protein complex of RNA interference
      (RNAi), is of great importance to the development of siRNAs with improved
      biological and potentially therapeutic function. Although various chemically
      modified siRNAs have been reported, relatively few studies with modified
      nucleobases exist. Here we describe the synthesis and hybridization properties of
      siRNAs bearing size-expanded RNA (xRNA) nucleobases and their use as a novel and
      systematic set of steric probes in RNAi. xRNA nucleobases are expanded by 2.4 A
      using benzo-homologation and retain canonical Watson-Crick base-pairing groups.
      Our data show that the modified siRNA duplexes display small changes in melting
      temperature (+1.4 to -5.0  degrees C); substitutions near the center are somewhat
      destabilizing to the RNA duplex, while substitutions near the ends are
      stabilizing. RNAi studies in a dual-reporter luciferase assay in HeLa cells
      revealed that xRNA nucleobases in the antisense strand reduce activity at some
      central positions near the seed region but are generally well tolerated near the
      ends. Most importantly, we observed that xRNA substitutions near the 3'-end
      increased activity over that of wild-type siRNAs. The data are analyzed in terms
      of site-dependent steric effects in RISC. Circular dichroism experiments show
      that single xRNA substitutions do not significantly distort the native A-form
      helical structure of the siRNA duplex, and serum stability studies demonstrated
      that xRNA substitutions protect siRNAs against nuclease degradation.

PMID- 22646661
TI  - Analysis of bisphenol A and alkylphenols in cereals by automated on-line solid
      phase extraction and liquid chromatography tandem mass spectrometry.
AB  - An on-line solid-phase extraction (SPE) following a liquid chromatography
      electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was
      established for the simultaneous analysis of bisphenol A (BPA), nonylphenol (NP),
      and octylphenol (OP) in cereals (including rice, maize, and wheat). The target
      compounds were extracted by acetonitrile, purified by an automated on-line SPE
      cartridge, and analyzed by LC-MS/MS under the negative-ion mode. Mean recoveries
      fortified at three concentration levels ranged from 81.6 to 115.7%, and the
      coefficient of variation ranged from 4.6 to 19.9% (n = 6). The limits of
      quantification (LOQs) of the method were 0.5, 0.5, and 0.25 MUg/kg for BPA, NP,
      and OP, respectively, in both rice and maize, while the LOQs in wheat were 0.5,
      1.25, and 0.5 MUg/kg for BPA, NP, and OP, respectively. This method was applied
      in the analysis of rice, maize, and wheat from a local market. As a result, NP
      occurred in all cereal samples at the concentration range of 9.4-1683.6 MUg/kg
      and BPA was detected in a few samples.

PMID- 22646662
TI  - Prenatal and perinatal risk factors of schizophrenia.
AB  - Schizophrenia could be considered the most severe of all psychiatric disorders.
      It shows a heterogeneous clinical picture and presents an etiopathogenesis that
      is not cleared sufficiently. Even if the etiopathogenesis remains a puzzle, there
      is a scientific consensus that it is an expression of interaction between
      genotype and environmental factors. In the present article, following a study of
      literature and the accumulated evidence, the role of prenatal and perinatal
      factors in the development of schizophrenia will be revised and synthesized. We
      think that better knowledge of the risk factors could be helpful not only for
      better comprehension of the pathogenesis but especially to optimize interventions
      for prevention of the disorder.

PMID- 22646663
TI  - Novel variants of HMW glutenin subunits from Aegilops section Sitopsis species in
      relation to evolution and wheat breeding.
AB  - BACKGROUND: High molecular weight glutenin subunits (HMW-GSs), encoded by the
      genes at Glu-1 loci in wheat and its related species, are significant in the
      determination of grain processing quality. However, the diversity and variations
      of HMW-GSs are relatively low in bread wheat. More interests are now focused on
      wheat wild relatives in Triticeae. The genus Aegilops represents an important
      germplasm for novel HWM-GSs and other useful genes for wheat genetic improvement.
      RESULTS: Six novel Glu-1 alleles and HMW-GSs were identified and characterized
      from three species of Aegilops section Sitopsis (S genome). Both open reading
      frames (ORFs) and promoter regions of these Glu-1 alleles were sequenced and
      characterized. The ORFs of Sitopsis Glu-1 genes are approximately 2.9 kb and 2.3
      kb for x-type and y-type subunits, respectively. Although the primary structures
      of Sitopsis HMW-GSs are similar to those of previously reported ones, all six x
      type or y-type subunits have the large fragment insertions. Our comparative
      analyses of the deduced amino acid sequences verified that Aegilops section
      Sitopsis species encode novel HMW-GSs with their molecular weights larger than
      almost all other known HMW-GSs. The Glu-1 promoter sequences share the high
      homology among S genome. Our phylogenetic analyses by both network and NJ tree
      indicated that there is a close phylogenetic evolutionary relationship of x-type
      and y-type subunit between S and D genome. CONCLUSIONS: The large molecular
      weight of HMW-GSs from S genome is a unique feature identified in this study.
      Such large subunits are resulted from the duplications of repetitive domains in
      Sitopsis HMW-GSs. The unequal crossover events are the most likely mechanism of
      variations in glutenin subunits. The S genome-encoded subunits, 1Dx2.2 and
      1Dx2.2* have independent origins, although they share similar evolutionary
      mechanism. As HMW-GSs play a key role in wheat baking quality, these large
      Sitopsis glutenin subunits can be used as special genetic resources for wheat
      quality improvement.

PMID- 22646664
TI  - The diagnostic yield of the first episode of a periodic health evaluation: a
      descriptive epidemiology study.
AB  - BACKGROUND: The benefits of a periodic health evaluation remain debatable. The
      incremental value added by such evaluations beyond the delivery of age
      appropriate screening and preventive medicine recommendations is unclear.
      METHODS: We retrospectively collected data on a cohort of consecutive patients
      presenting for their first episode of a comprehensive periodic health evaluation.
      We abstracted data on new diagnoses that were identified during this single
      episode of care and that were not trivial (i.e., required additional testing or
      intervention). RESULTS: The cohort consisted of 491 patients. The rate of new
      diagnoses per this single episode of care was 0.9 diagnoses per patient. The
      majority of these diagnoses was not prompted by patients' complaints (71%) and
      would not have been identified by screening guidelines (51%). Men (odds ratio
      2.67; 95% CI, 1.76, 4.03) and those with multiple complaints at presentation
      (odds ratio 1.12; 95% CI, 1.05, 1.19) were more likely to receive a clinically
      relevant diagnosis at the conclusion of the visit. Age was not a predictor of
      receiving a diagnosis in this cohort. CONCLUSION: The first episode of a
      comprehensive periodic health evaluation may reveal numerous important diagnoses
      or risk factors that are not always identified through routine screening.

PMID- 22646665
TI  - Depression, anxiety and quality-of-life among relatives of patients with severe
      brain injury: the acute phase.
AB  - PRIMARY OBJECTIVE: To investigate the emotional well-being of relatives of
      patients with a severe brain injury in the acute setting, as well as risk factors
      associated with high anxiety and depression scores and impaired quality-of-life.
      RESEARCH DESIGN: Clinical convenience sample. METHODS AND PROCEDURES:
      Participants included 45 relatives of patients with severe brain injury recruited
      at a NICU. All relatives completed selected scales from the SCL-90-R and SF-36 ~
      14 days after injury. Data concerning the condition of the patient were also
      collected. MAIN OUTCOME AND RESULTS: Of the relatives, 51% and 69% reported
      anxiety and depression, respectively, as well as significantly impaired quality
      of-life compared to normal reference populations. Regression analysis revealed
      that up to 20% of the variance in depression and anxiety scores could be
      explained by the CRASH 2 Mortality prediction. CONCLUSIONS: The majority of the
      relatives had severely impaired quality-of-life and symptoms of anxiety and
      depression during the patient's NICU stay. Future research is required to explore
      stressors and evaluate effects of psychological intervention in the acute
      setting.

PMID- 22646666
TI  - Involvement of the endogenous hydrogen sulfide/Ca(v) 3.2 T-type Ca2+ channel
      pathway in cystitis-related bladder pain in mice.
AB  - BACKGROUND AND PURPOSE: Hydrogen sulfide (H(2) S), generated by enzymes such as
      cystathionine-gamma-lyase (CSE) from L-cysteine, facilitates pain signals by
      activating the Ca(v) 3.2 T-type Ca(2+) channels. Here, we assessed the
      involvement of the CSE/H(2) S/Ca(v) 3.2 pathway in cystitis-related bladder pain.
      EXPERIMENTAL APPROACH: Cystitis was induced by i.p. administration of
      cyclophosphamide in mice. Bladder pain-like nociceptive behaviour was observed
      and referred hyperalgesia was evaluated using von Frey filaments. Phosphorylation
      of ERK in the spinal dorsal horn was determined immunohistochemically following
      intravesical administration of NaHS, an H(2) S donor. KEY RESULTS:
      Cyclophosphamide caused cystitis-related symptoms including increased bladder
      weight, accompanied by nociceptive changes (bladder pain-like nociceptive
      behaviour and referred hyperalgesia). Pretreatment with DL-propargylglycine, an
      inhibitor of CSE, abolished the nociceptive changes and partly prevented the
      increased bladder weight. CSE protein in the bladder was markedly up-regulated
      during development of cystitis. Mibefradil or NNC 55-0396, blockers of T-type
      Ca(2+) channels, administered after the symptoms of cystitis appeared, reversed
      the nociceptive changes. Further, silencing of Ca(v) 3.2 protein by repeated
      intrathecal administration of mouse Ca(v) 3.2-targeting antisense
      oligodeoxynucleotides also significantly attenuated the nociceptive changes, but
      not the increased bladder weight. Finally, the number of cells staining positive
      for phospho-ERK was increased in the superficial layer of the L6 spinal cord
      after intravesical administration of NaHS, an effect inhibited by NNC 55-0396.
      CONCLUSION AND IMPLICATIONS: Endogenous H(2) S, generated by up-regulated CSE,
      caused bladder pain and referred hyperalgesia through the activation of Ca(v) 3.2
      channels, one of the T-type Ca(2+) channels, in mice with cyclophosphamide
      induced cystitis.

PMID- 22646667
TI  - Examining the impact of psychiatric diagnosis and comorbidity on the medical
      lethality of adolescent suicide attempts.
AB  - Specific psychiatric diagnoses and comorbidity patterns were examined to
      determine if they were related to the medical lethality of suicide attempts among
      adolescents presenting to an urban general hospital (N=375). Bivariate analysis
      showed that attempters with substance abuse disorders had higher levels of
      lethality than attempters without substance abuse. Regression results indicated
      having depression comorbid with any other diagnosis was not associated with
      medical lethality. However, having a substance abuse disorder was associated with
      higher suicide attempt lethality, highlighting the importance of substance abuse
      as a risk factor for lethal suicide attempts in adolescents. This finding
      stimulates critical thinking around the understanding of suicidal behavior in
      youth and the development and implementation of treatment strategies for suicidal
      adolescents with substance abuse disorders.

PMID- 22646668
TI  - Block periodization of high-intensity aerobic intervals provides superior
      training effects in trained cyclists.
AB  - The purpose of this study was to compare the effect of two different methods of
      organizing endurance training in trained cyclists. One group of cyclists
      performed block periodization, wherein the first week constituted five sessions
      of high-intensity aerobic training (HIT), followed by 3 weeks of one weekly HIT
      session and focus on low-intensity training (LIT) (BP; n = 10, VO2max  = 62 +/- 2
      mL/kg/min). Another group of cyclists performed a more traditional organization,
      with 4 weeks of two weekly HIT sessions interspersed with LIT (TRAD; n = 9,
      VO2max  = 63 +/- 2 mL/kg/min). Similar volumes of both HIT and LIT was performed
      in the two groups. While BP increased VO2max , peak power output (Wmax) and power
      output at 2 mmol/L [la(-)] by 4.6 +/- 3.7%, 2.1 +/- 2.8%, and 10 +/- 12%,
      respectively (P < 0.05), no changes occurred in TRAD. BP showed relative
      improvements in VO2max compared with TRAD (P < 0.05). Mean effect size (ES) of
      the relative improvement in VO2max , Wmax , and power output at 2 mmol/L [la(-)]
      revealed large to moderate effects of BP training compared with TRAD training (ES
      = 1.34, ES = 0.85, and ES = 0.71, respectively). The present study suggests that
      block periodization of training provides superior adaptations to traditional
      organization during a 4-week endurance training period, despite similar training
      volume and intensity.

PMID- 22646669
TI  - HPLC-assisted automated oligosaccharide synthesis.
AB  - A standard HPLC was adapted to polymer supported oligosaccharide synthesis.
      Solution-based reagents are delivered using a software-controlled solvent
      delivery system. The reaction progress and completion can be monitored in real
      time using a standard UV detector. All steps of oligosaccharide assembly
      including loading, glycosylation, deprotection, and cleavage can be performed
      using this setup.

PMID- 22646671
TI  - Variability in disease burden and management of rheumatic fever and rheumatic
      heart disease in two regions of tropical Australia.
AB  - BACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD)
      contribute to Aboriginal Australian and Torres Strait Islander health
      disadvantage. At the time of this study, specialist ARF/RHD care in the Kimberley
      region of Western Australia was delivered by a broad range of providers. In
      contrast, in Far North Queensland (FNQ), a single-provider model was used as part
      of a coordinated RHD control programme. AIMS: To review ARF/RHD management in the
      Kimberley and FNQ to ascertain whether differing models of service delivery are
      associated with different disease burden and patient care. METHODS: An audit of
      ARF/RHD management. Classification and clinical management data were abstracted
      from health records, specialist letters, echocardiograms and regional registers
      using a standardised data collection tool. RESULTS: Four hundred and seven
      patients were identified, with 99% being Aboriginal and/or Torres Strait
      Islanders. ARF without RHD was seen in 0.4% of Aboriginal and/or Torres Strait
      Islander residents and RHD in 1.1%. The prevalence of RHD was similar in both
      regions but with more severe disease in the Kimberley. More FNQ RHD patients had
      specialist review within recommended time frames (67% vs 45%, chi(2) , P <
      0.001). Of patients recommended benzathine penicillin secondary prophylaxis,
      17.7% received >=80% of scheduled doses in the preceding 12 months. Prescription
      and delivery of secondary prophylaxis was greater in FNQ. CONCLUSIONS: FNQ's
      single-provider model of specialist care and centralised RHD control programme
      were associated with improved patient care and may partly account for the fewer
      cases of severe disease and reduced surgical procedures and other interventions
      observed in this region.

PMID- 22646670
TI  - Detection of circulating tumor cells in blood of metastatic breast cancer
      patients using a combination of cytokeratin and EpCAM antibodies.
AB  - BACKGROUND: Circulating tumor cells (CTCs) are detectable in peripheral blood of
      metastatic breast cancer patients (MBC). In this paper we evaluate a new CTC
      separation method based on a combination of anti-EpCAM- and anti-cytokeratin
      magnetic cell separation with the aim to improve CTC detection with low target
      antigen densities. METHODS: Blood samples of healthy donors spiked with breast
      cancer cell line HCC1937 were used to determine accuracy and precision of the
      method. 10 healthy subjects were examined to evaluate specificity. CTC counts in
      59 patients with MBC were measured to evaluate the prognostic value on overall
      survival. RESULTS: Regression analysis of numbers of recovered vs. spiked HCC1937
      cells yielded a coefficient of determination of R(2) = 0.957. The average
      percentage of cell recovery was 84%. The average within-run coefficient of
      variation for spiking of 185, 85 and 30 cells was 14%. For spiking of 10 cells
      the within-run CV was 30%. No CTCs were detected in blood of 10 healthy subjects
      examined. A standard threshold of 5 CTC/7.5 ml blood as a cut-off point between
      risk groups led to a highly significant prognostic marker (p < 0.001). To assess
      the prognostic value of medium CTC levels we additionally considered a low (CTC
      L: 0 CTC), a medium (CTC-M: 1-4 CTC) and a high risk group (CTC-H: >=5 CTC). The
      effect of this CTC-LMH marker on overall survival was significant as well (p <
      0.001). A log-ratio test performed to compare the model with 3 vs. the model with
      2 risk groups rejected the model with 2 risk groups (p = 0.026). For CTC as a
      count variable, we propose an offset reciprocal transformation 1/(1 + x) for
      overall survival prediction (p < 0.001). CONCLUSIONS: We show that our CTC
      detection method is feasible and leads to accurate and reliable results. Our data
      suggest that a refined differentiation between patients with different CTC levels
      is reasonable.

PMID- 22646672
TI  - Mean platelet volume in pediatric chronic kidney diseases.

PMID- 22646685
TI  - Top-down and bottom-up approaches to motor skill assessment of children: are
      child-report and parent-report perceptions predictive of children's performance
      based assessment results?
AB  - BACKGROUND/ AIM: Therapists use different types of tests, scales, and instruments
      to assess children's motor skills, including those classified as being top-down
      and bottom-up. The aim of the study was to investigate the ability of measures of
      children's motor skill performance from the perspectives of children and parents
      (a type of top-down assessment) to predict children's performance-based motor
      ability test results (a type of bottom-up assessment). METHODS: A convenience
      sample of 38 children and parents was recruited from Victoria, Australia. Motor
      skill performance was evaluated from a top-down perspective using the Physical
      Self-Description Questionnaire (PSDQ) and the Movement Assessment Battery for
      Children--Second Edition (MABC-2) Checklist to measure children's and parents'
      perspectives respectively. Motor skill performance was also evaluated from a
      bottom-up approach using the Bruininks-Oseretsky Test of Motor Proficiency-
      Second Edition (BOT-2). Data were analyzed using multiple linear regression
      analysis to determine whether the PSDQ or MABC-2 Checklist was predictive of the
      children's BOT-2 performance results. RESULTS: Two predictive relationships were
      identified based on parents' perspectives, where the total score of the MABC-2
      Checklist was found to be a significant predictor of the BOT-2 Manual
      Coordination motor composite score, accounting for 8.35% of its variance, and the
      BOT-2 Strength and Agility motor composite score, accounting for 11.6% of its
      variance. No predictive relationships were identified between the children's self
      report PSDQ perspectives and the BOT-2 performance scores. CONCLUSIONS:
      Therapists are encouraged to utilize a combination of top-down and bottom-up
      approaches and purposefully to seek parents' and children's perspectives when
      evaluating children's motor skill performance.

PMID- 22646686
TI  - Alcohol licensing in Scotland: a historical overview.
AB  - AIM:   This paper provides a historical overview of licensing law in Scotland. It
      seeks to put important contemporary policy developments into their historical
      context and to draw attention to key themes in licensing policy debates across
      the United Kingdom. DESIGN:   Based on a survey of statutes, commissions of
      enquiry and consumption and retail data, this paper draws together historical
      evidence to present a synopsis of Scottish licensing history. SETTINGS:   The
      article focuses on Scotland, but also discusses UK-wide licensing policy over a
      250-year period. FINDINGS:   Scottish licensing has diverged from licensing in
      England and Wales and has addressed some historical licensing weaknesses,
      including problems of accountability, overprovision and systemic oversight
      regarding off-sales. Distinctive features of current Scottish legislation include
      public health protection as a statutory licensing objective; local Licensing
      Forums and Licensing Standards Officers; a requirement for explicit policies on
      the 'overprovision' of licensed premises; mandatory restrictions on price
      promotions in the on- and off-trades; and limitations on opening hours for off
      licences. CONCLUSION:   Scotland has developed alcohol policies several times
      addressing long-standing licensing weaknesses throughout the United Kingdom. Some
      Scottish alcohol policies have later become the norm in England and Wales.

PMID- 22646687
TI  - Haemorrhoids: 21st-century management.

PMID- 22646688
TI  - Human skin model containing melanocytes: essential role of keratinocyte growth
      factor for constitutive pigmentation-functional response to alpha-melanocyte
      stimulating hormone and forskolin.
AB  - To study human skin pigmentation in a physiological in vitro model, we developed
      a pigmented reconstructed skin reproducing the three-dimensional architecture of
      the melanocyte environment and the interactions of melanocyte with its cellular
      partners, keratinocytes, and fibroblasts. Co-seeding melanocytes and
      keratinocytes onto a fibroblast-populated collagen matrix led to a correct
      integration of melanocytes within the epidermal basal layer, but melanocytes
      remained amelanotic even after supplementation with promelanogenic factors.
      Interestingly, normalization of keratinocyte differentiation using keratinocyte
      growth factor instead of epidermal growth factor finally allowed an active
      pigmentary system to develop, as shown by the expression of key melanogenic
      markers, the production, and transfer of melanosome-containing melanin into
      keratinocytes. Various degrees of constitutive pigmentation were reproduced using
      melanocytes from different skin phenotypes. Furthermore, induction of
      pigmentation was achieved by treatment with known propigmenting molecules,
      alphaMSH and forskolin, thus demonstrating the functionality of the pigmentary
      system. This pigmented full-thickness skin model therefore represents a highly
      relevant tool to study the role of cell-cell, cell-matrix, and mesenchymal
      epithelial interactions in the control of skin pigmentation.

PMID- 22646689
TI  - Allosteric mutants show that PrfA activation is dispensable for vacuole escape
      but required for efficient spread and Listeria survival in vivo.
AB  - The transcriptional regulator PrfA controls key virulence determinants of the
      facultative intracellular pathogen Listeria monocytogenes. PrfA-dependent gene
      expression is strongly induced within host cells. While the basis of this
      activation is unknown, the structural homology of PrfA with the cAMP receptor
      protein (Crp) and the finding of constitutively activated PrfA* mutants suggests
      it may involve ligand-induced allostery. Here, we report the identification of a
      solvent-accessible cavity within the PrfA N-terminal domain that may accommodate
      an activating ligand. The pocket occupies a similar position to the cAMP binding
      site in Crp but lacks the cyclic nucleotide-anchoring motif and has its entrance
      on the opposite side of the beta-barrel. Site-directed mutations in this pocket
      impaired intracellular PrfA-dependent gene activation without causing extensive
      structural/functional alterations to PrfA. Two substitutions, L48F and Y63W,
      almost completely abolished intracellular virulence gene induction and thus
      displayed the expected phenotype for allosteric activation-deficient PrfA
      mutations. Neither PrfA(allo) substitution affected vacuole escape and initial
      intracellular growth of L. monocytogenes in epithelial cells and macrophages but
      caused defective cell-to-cell spread and strong attenuation in mice. Our data
      support the hypothesis that PrfA is allosterically activated during intracellular
      infection and identify the probable binding site for the effector ligand. They
      also indicate that PrfA allosteric activation is not required for early
      intracellular survival but is essential for full Listeria virulence and
      colonization of host tissues.

PMID- 22646691
TI  - Two photon dissociation dynamics of NO2 and NO2 + H2O.
AB  - To explore the dynamics of OH formation from two photon absorbed NO(2) with
      H(2)O, a high-level multiconfigurational perturbation theory was used to map the
      potential energy profiles of NO(2) dissociation to O ((1)D) + NO (X(2)Pi), and
      subsequent hydrogen abstraction producing 2OH (X(2)Pi) + NO (X(2)Pi) in the
      highly excited S(PP) (E(2)A', (2)pipi*) state. The ground state NO(2) is promoted
      to populate in the S(NP1) (A(2)A", (2)npi*) intermediate state by one photon
      absorption at ~440 nm, one thousandth of which is further excited to S(PP)
      (E(2)A', (2)pipi*) state and undergoes a medium-sized barrier (~11.0 kcal/mol) to
      give rise to OH radicals. In comparison with the hydrogen abstraction reaction in
      highly vibrationally excited NO(2) ground state, two photon absorption
      facilitates NO(2) dissociation to O ((1)D) and O ((1)D) + H(2)O -> 2OH (X(2)Pi)
      but results in low quantum yield of NO(2)** since there is a weak absorption upon
      the second beam light at ~440 nm. It can be concluded that the reaction of two
      photon absorbed NO(2) with H(2)O makes negligible contributions to the formation
      of OH radicals. In contrast, single photon absorption at <554 nm is a possible
      process on the basis of the present and previous computations.

PMID- 22646690
TI  - Examining electrodermal hyporeactivity as a marker of externalizing
      psychopathology: a twin study.
AB  - Literature suggests that reduced electrodermal reactivity (EDR) is related to
      externalizing problems. However, the genetic and environmental etiology of this
      association is unknown. Using a standard habituation paradigm, we measured
      responses to 15 loud tones in four cohorts of adolescent twins (N = 2,129). We
      quantified EDR as the average size of elicited responses (amplitude) and by
      counting the number of skin conductance responses (frequency). Externalizing
      liability was indexed through a general factor underlying substance-related
      problems and antisocial behavior. Response frequency, but not mean amplitude, was
      inversely associated with externalizing liability in each twin cohort. Biometric
      modeling revealed that most of the overlap between response frequency and
      externalizing liability was due to genetic influences common to both phenotypes.
      It is argued that neurological mechanisms involved in habituation may shed light
      on the etiology of psychopathology.

PMID- 22646692
TI  - Complications in postacute care are associated with persistent delirium.
AB  - OBJECTIVES: To investigate whether complications in postacute care (PAC) are
      associated with delirium persistence 30 days after PAC admission. DESIGN:
      Observational cohort study. SETTING: Eight Boston-area PAC facilities.
      PARTICIPANTS: Three hundred fifty individuals with delirium at PAC admission.
      MEASUREMENTS: Participants were interviewed at PAC admission and 30 days later.
      Delirium presence was determined using the Confusion Assessment Method. Medical
      record reviews were performed to ascertain new cardiac, noncardiac, and geriatric
      syndrome complications in PAC. Complication status was also determined 30 days
      after admission or at PAC discharge, whichever came first. RESULTS: Participants
      (mean age 83.6, 66% female) experienced the following incidence of PAC
      complications: cardiac complications (7%), noncardiac complications (21%), and
      geriatric syndrome complications (39%). Delirium persisted in 56% of participants
      1 month after PAC admission. Neither cardiac nor noncardiac complications were
      associated with delirium persistence. Delirium persistence at 1 month was
      significantly greater in participants, with more geriatric syndrome complications
      (no complications, 51%; one complication 61%; >= 2 complications, 100%, adjusted
      P = .048). There was also a trend toward greater delirium persistence in
      participants with unresolved geriatric syndrome complications (no complications,
      51%; resolved complication, 61%; unresolved complication, 68%; adjusted P = .10).
      CONCLUSION: Geriatric syndrome complications are common in individuals admitted
      to PAC with delirium and are associated with persistence of delirium 1 month
      later. Proactively addressing risk factors for geriatric syndromes may improve
      outcomes of vulnerable individuals in PAC.

PMID- 22646693
TI  - Dietary supplementation with Ipomoea aquatica (whole leaf powder) attenuates
      maternal and fetal oxidative stress in streptozotocin-diabetic rats.
AB  - BACKGROUND: The rate of congenital anomalies, as well as morbidity and mortality
      of both the mother and fetus, is increased in diabetic pregnancy. Oxidative
      stress (OS) has been implicated in these effects because of the beneficial
      effects of several antioxidants in diabetic embryopathy. In the present study, we
      assessed attenuation of maternal and fetal OS and diabetic embryopathy by Ipomoea
      aquatica Forsk. (Convolvulaceae). METHODS: Pregnant rats were divided into four
      groups: Group I, untreated non-diabetic control; Group II, rats fed a 2%I.
      aquatica (IA)-supplemented diet; Group III, streptozotocin (STZ)-diabetic rats
      fed a normal diet; Group IV, STZ-diabetic rats fed an IA-supplemented diet. Rats
      were rendered diabetic with a single injection of STZ (40 mg/kg) on gestational
      day (GD) 4. Dams were killed on GD20 and markers of OS were determined in the
      maternal liver and fetal brain and liver. RESULTS: Embryopathy increased
      significantly in STZ-diabetic rats (by 40% versus control), but IA
      supplementation provided significant protection (36% reduction in embryopathy in
      the IA group versus the STZ-diabetic group). Interestingly, IA supplementation
      significantly offset diabetes-associated OS in the maternal liver, as evidenced
      by reductions in malondialdehyde (MDA; 25% reduction versus STZ-diabetes) and
      reactive oxygen species (ROS; 72% reduction) and increases in glutathione (53%
      reduction) and total thiols (45% reduction). In addition, IA supplementation
      offered significant protection against diabetes-induced OS in the fetal brain and
      liver, as evidenced by increased levels of antioxidant molecules and enzymes and
      reductions in ROS and MDA compared with fetuses from STZ-diabetic rats.
      CONCLUSIONS: The data suggest that IA supplementation during pregnancy provides
      considerable protection against diabetes-induced OS in the mother and fetus.
      Thus, I. aquatica may be an effective therapeutic supplement.

PMID- 22646694
TI  - Influence of gallic acid and tannic acid on the mechanical and barrier properties
      of wheat gluten films.
AB  - Vital wheat gluten, a byproduct of wheat starch production, is a highly
      functional ingredient having a unique viscoelasticity that makes it ideal for the
      production of edible biodegradable films. However, its functional properties must
      be modified to ensure sufficient strength and elasticity, in addition to water
      vapor barrier properties. In this study, vital gluten was modified using tannic
      and gallic acid. It was found that the addition of tannic acid resulted in
      stiffer, more resistant, and less resilient and flexible films, having as well
      decreased water vapor permeability. Tannic acid containing films became reddish
      brown, whereas gallic acid addition did not have an influence on the film
      appearance. Films containing gallic acid became more elastic. Gallic acid was
      found to potentially act like a plasticizer. Scanning electron microscopy was
      used to investigate the ultrastructure of the produced films.

PMID- 22646695
TI  - A new stoichiometric miniaturization strategy for screening of industrial
      microbial strains: application to cellulase hyper-producing Trichoderma reesei
      strains.
AB  - BACKGROUND: During bioprocess development, secondary screening is a key step at
      the boundary between laboratory and industrial conditions. To ensure an effective
      high-throughput screening, miniaturized laboratory conditions must mimic
      industrial conditions, especially for oxygen transfer, feeding capacity and pH
      stabilization. RESULTS: A feeding strategy has been applied to develop a simple
      screening procedure, in which a stoichiometric study is combined with a standard
      miniaturization procedure. Actually, the knowledge of all nutriments and base or
      acid requirements leads to a great simplification of pH stabilization issue of
      miniaturized fed-batch cultures. Applied to cellulase production by Trichoderma
      reesei, this strategy resulted in a stoichiometric mixed feed of carbon and
      nitrogen sources. While keeping the pH between shake flask and stirred bioreactor
      comparable, the developed shake flask protocol reproduced the strain behaviour
      under stirred bioreactor conditions. Compared to a an already existing
      miniaturized shake flasks protocol, the cellulase concentration was increased 5
      fold, reaching about 10 g L-1. Applied to the secondary screening of several
      clones, the newly developed protocol succeeded in selecting a clone with a high
      industrial potential. CONCLUSIONS: The understanding of a bioprocess
      stoichiometry contributed to define a simpler and more effective miniaturization.
      The suggested strategy can potentially be applied to other fed-batch processes,
      for the screening of either strain collections or experimental conditions.

PMID- 22646697
TI  - OX40 ligand and OX40 are increased in atopic dermatitis lesions but do not
      correlate with clinical severity.
AB  - BACKGROUND: The interaction between the OX40 ligand (OX40L) and OX40 has been
      suggested to have pathogenetic significance in atopic dermatitis (AD). OBJECTIVE:
      The purpose of this study was to investigate the expression and relevance of
      OX40L and OX40 in AD skin. METHODS: OX40L and OX40 were stained
      immunohistochemically on the cryosections of the lesional and non-lesional skin
      of 17 subjects with moderate-to-severe AD and of 10 patients with psoriasis
      vulgaris. Phorbol myristate acetate (PMA) stimulated keratinocytes and cell
      membrane preparations from PMA-stimulated keratinocytes or LAD-2 mast cells were
      incubated with peripheral blood mononuclear cells (PBMC) in the presence or
      absence of blocking monoclonal antibodies to OX40L, CD30L or ICAM-1. RESULTS: We
      show for the first time that the staining intensity of OX40L and the number of
      OX40(+) cells are significantly greater in the lesional dermis than in the
      healthy-looking dermis in AD (P < 0.001 in both comparisons) and also in
      psoriasis (P = 0.01 and P < 0.001 respectively), but neither molecule correlate
      significantly with the clinical severity of AD. Living keratinocytes and cell
      membranes from LAD-2 mast cells and keratinocytes increased the PBMC
      proliferation response. Anti-OX40L antibody inhibited, in a similar fashion as
      anti-ICAM-1 and anti-CD30L, PBMC proliferation induced by LAD-2 membranes, but
      stimulated that induced by keratinocytes. CONCLUSION: Our findings provide
      evidence for the involvement of OX40 and OX40L in the pathogenesis of AD though
      they are not specific to AD and in vitro results suggest complex interaction.

PMID- 22646696
TI  - Identification of ligand analogues that control c-di-GMP riboswitches.
AB  - Riboswitches for the bacterial second messenger c-di-GMP control the expression
      of genes involved in numerous cellular processes such as virulence, competence,
      biofilm formation, and flagella synthesis. Therefore, the two known c-di-GMP
      riboswitch classes represent promising targets for developing novel modulators of
      bacterial physiology. Here, we examine the binding characteristics of circular
      and linear c-di-GMP analogues for representatives of both class I and II c-di-GMP
      riboswitches derived from the pathogenic bacterium Vibrio choleae (class I) and
      Clostridium difficile (class II). Some compounds exhibit values for apparent
      dissociation constant (K(D)) below 1 MUM and associate with riboswitch RNAs
      during transcription with a speed that is sufficient to influence riboswitch
      function. These findings are consistent with the published structural models for
      these riboswitches and suggest that large modifications at various positions on
      the ligand can be made to create novel compounds that target c-di-GMP
      riboswitches. Moreover, we demonstrate the potential of an engineered allosteric
      ribozyme for the rapid screening of chemical libraries for compounds that bind c
      di-GMP riboswitches.

PMID- 22646698
TI  - The selective sphingosine 1-phosphate receptor modulator BAF312 redirects
      lymphocyte distribution and has species-specific effects on heart rate.
AB  - BACKGROUND AND PURPOSE: BAF312 is a next-generation sphingosine 1-phosphate (S1P)
      receptor modulator, selective for S1P(1)  and S1P(5 ) receptors. S1P(1) 
      receptors are essential for lymphocyte egress from lymph nodes and a drug target
      in immune-mediated diseases. Here, we have characterized the immunomodulatory
      potential of BAF312 and the S1P receptor-mediated effects on heart rate using
      preclinical and human data. EXPERIMENTAL APPROACH: BAF312 was tested in a rat
      experimental autoimmune encephalomyelitis (EAE) model. Electrophysiological
      recordings of G-protein-coupled inwardly rectifying potassium (GIRK) channels
      were carried out in human atrial myocytes. A Phase I multiple-dose trial studied
      the pharmacokinetics, pharmacodynamics and safety of BAF312 in 48 healthy
      subjects. KEY RESULTS: BAF312 effectively suppressed EAE in rats by internalizing
      S1P(1)  receptors, rendering them insensitive to the egress signal from lymph
      nodes. In healthy volunteers, BAF312 caused preferential decreases in CD4(+)  T
      cells, T(naive) , T(central memory)  and B cells within 4-6 h. Cell counts
      returned to normal ranges within a week after stopping treatment, in line with
      the elimination half-life of BAF312. Despite sparing S1P(3)  receptors
      (associated with bradycardia in mice), BAF312 induced rapid, transient (day 1
      only) bradycardia in humans. BAF312-mediated activation of GIRK channels in human
      atrial myocytes can fully explain the bradycardia. CONCLUSION AND IMPLICATIONS:
      This study illustrates species-specific differences in S1P receptor specificity
      for first-dose cardiac effects. Based on its profound but rapidly reversible
      inhibition of lymphocyte trafficking, BAF312 may have potential as a treatment
      for immune-mediated diseases.

PMID- 22646699
TI  - Update on immunomodulatory drugs (IMiDs) in hematologic and solid malignancies.

PMID- 22646702
TI  - Positive changes in Japanese breast cancer survivors: a qualitative study.
AB  - Despite traumatic experiences of cancer, survivors often report positive changes.
      Since little research has been conducted into such changes among Japanese breast
      cancer survivors, our knowledge is minimal. This qualitative study aimed to
      explore the nature of the positive changes among this group. A thematic analysis
      suggested that participants had experienced seven types of positive change:
      Attitudinal changes towards life, strengthening trust in family and friends,
      increased appreciation of life, self-development, future perspectives, education
      for friends, and efforts towards bodily change. Awareness of vulnerability in
      life, received social support and social comparisons appear to trigger some of
      the positive changes.

PMID- 22646701
TI  - Neural correlates of being imitated: an EEG study in preverbal infants.
AB  - A foundational aspect of early social-emotional development is the ability to
      detect and respond to the actions of others who are coordinating their behavior
      with that of the self. Behavioral work in this area has found that infants show
      particular preferences for adults who are imitating them rather than adults who
      are carrying out noncontingent or mismatching actions. Here, we explore the
      neural processes related to this tendency of infants to prefer others who act
      like the self. Electroencephalographic (EEG) signals were recorded from 14-month
      old infants while they were observing actions that either matched or mismatched
      the action the infant had just executed. Desynchronization of the EEG mu rhythm
      was greater when infants observed an action that matched their own most recently
      executed action. This effect was strongest immediately prior to the culmination
      of the goal of the observed action, which is consistent with recent ideas about
      the predictive nature of brain responses during action observation.

PMID- 22646700
TI  - Transcriptome of the adult female malaria mosquito vector Anopheles albimanus.
AB  - BACKGROUND: Human Malaria is transmitted by mosquitoes of the genus Anopheles.
      Transmission is a complex phenomenon involving biological and environmental
      factors of humans, parasites and mosquitoes. Among more than 500 anopheline
      species, only a few species from different branches of the mosquito evolutionary
      tree transmit malaria, suggesting that their vectorial capacity has evolved
      independently. Anopheles albimanus (subgenus Nyssorhynchus) is an important
      malaria vector in the Americas. The divergence time between Anopheles gambiae,
      the main malaria vector in Africa, and the Neotropical vectors has been estimated
      to be 100 My. To better understand the biological basis of malaria transmission
      and to develop novel and effective means of vector control, there is a need to
      explore the mosquito biology beyond the An. gambiae complex. RESULTS: We
      sequenced the transcriptome of the An. albimanus adult female. By combining
      Sanger, 454 and Illumina sequences from cDNA libraries derived from the midgut,
      cuticular fat body, dorsal vessel, salivary gland and whole body, we generated a
      single, high-quality assembly containing 16,669 transcripts, 92% of which mapped
      to the An. darlingi genome and covered 90% of the core eukaryotic genome.
      Bidirectional comparisons between the An. gambiae, An. darlingi and An. albimanus
      predicted proteomes allowed the identification of 3,772 putative orthologs. More
      than half of the transcripts had a match to proteins in other insect vectors and
      had an InterPro annotation. We identified several protein families that may be
      relevant to the study of Plasmodium-mosquito interaction. An open source
      transcript annotation browser called GDAV (Genome-Delinked Annotation Viewer) was
      developed to facilitate public access to the data generated by this and future
      transcriptome projects. CONCLUSIONS: We have explored the adult female
      transcriptome of one important New World malaria vector, An. albimanus. We
      identified protein-coding transcripts involved in biological processes that may
      be relevant to the Plasmodium lifecycle and can serve as the starting point for
      searching targets for novel control strategies. Our data increase the available
      genomic information regarding An. albimanus several hundred-fold, and will
      facilitate molecular research in medical entomology, evolutionary biology,
      genomics and proteomics of anopheline mosquito vectors. The data reported in this
      manuscript is accessible to the community via the VectorBase website
      (http://www.vectorbase.org/Other/AdditionalOrganisms/).

PMID- 22646703
TI  - Increase in nephrology advanced trainee numbers in Australia and associated
      reduction in clinical exposure over the past decade.
AB  - BACKGROUND: Advanced training in nephrology should provide broad experience in
      all aspects of nephrology. In Australia, the Specialist Advisory Committee in
      Nephrology oversees nephrology training, and recent increases in advanced trainee
      numbers have led to concern about dilution of training experience. No study has
      examined variations in clinical exposure for nephrology trainees in Australia.
      AIM: To assess the changes in nephrology advanced training in Australia with
      respect to trainee numbers and exposure to patients and procedures over the past
      10 years. METHODS: A retrospective study was performed by obtaining all available
      Royal Australasian College of Physician supervisor reports from 2000 to 2010 to
      determine differences in clinical exposure and procedures performed by nephrology
      trainees. RESULTS: Five hundred and forty-two reports were reviewed involving 208
      nephrology trainees in Australia across 53 different training sites. In 2000, 22
      trainees were undertaking a core clinical year of training. Trainee numbers have
      steadily risen from 33 in 2004 to 84 in 2010. The greatest increases have
      occurred in New South Wales, Victoria and Queensland (sixfold, threefold and
      fivefold increases respectively). Trainee exposure to dialysis patients has
      gradually decreased in the past decade. The average number per trainee per year
      in 2000 compared with 2010 were 66 versus 43 (P = 0.02) and 28 versus 16 (P =
      0.01) for haemodialysis and peritoneal dialysis respectively. Acute kidney injury
      cases per trainee showed a gradual nonsignificant reduction over time and average
      procedural numbers per trainee decreased significantly from 2000 to 2010 with
      fewer temporary dialysis catheters inserted per year (39 vs 10, P < 0.01) and
      fewer renal biopsies performed per year (65 vs 41, P < 0.01). The proportion of
      trainees working in a hospital that does not provide exposure to acute
      transplantation has steadily increased from 15% in 2003 to 44% in 2010.
      CONCLUSIONS: There has been a dramatic and significant increase in nephrology
      advanced trainee numbers over the past decade at a more rapid rate than the
      growth in dialysis and transplant patient numbers. This study suggests that
      training experience has diminished over the past decade and supports a 3-year
      core clinical nephrology training programme in Australia.

PMID- 22646704
TI  - New class of tetradentate beta-diketonate-europium complexes that can be
      covalently bound to proteins for time-gated fluorometric application.
AB  - Luminescent lanthanide complexes that can be covalently bound to proteins have
      shown great utility as biolabels for highly sensitive time-gated luminescence
      bioassays in clinical diagnostics and biotechnology discoveries. In this work,
      three new tetradentate beta-diketonate-europium complexes that can be covalently
      bound to proteins to display strong and long-lived Eu(3+) luminescence, 1,2
      bis[4'-(1",1",1",2",2",3",3"-heptafluoro-4",6"-hexanedion-6"-yl)-benzyl]-4
      chlorosulfobenzene-Eu(3+) (BHHBCB-Eu(3+)), 1,2-bis[4'-(1",1",1",2",2"-pentafluoro
      3",5"-pentanedion-5"-yl)-benzyl]-4-chlorosulfobenzene-Eu(3+) (BPPBCB-Eu(3+)), and
      1,2-bis[4'-(1",1",1"-trifluoro-2",4"-butanedion-4"-yl)-benzyl]-4
      chlorosulfobenzene-Eu(3+) (BTBBCB-Eu(3+)), have been designed and synthesized as
      biolabels for time-gated luminescence bioassay applications. The luminescence
      spectroscopy characterizations of the aqueous solutions of three complex-bound
      bovine serum albumin reveal that BHHBCB-Eu(3+) has the strongest luminescence
      with the largest quantum yield (40%) and longest luminescence lifetime (0.52 ms)
      among the complexes, which is superior to the other currently available europium
      biolabels. The BHHBCB-Eu(3+)-labeled streptavidin was prepared and used for both
      the time-gated luminescence immunoassay of human prostate specific antigen and
      the time-gated luminescence microscopy imaging of a pathogenic microorganism
      Cryptosporidium muris . The results demonstrated the practical utility of the new
      Eu(3+) complex-based biolabel for time-gated luminescence bioassay applications.

PMID- 22646705
TI  - Assessment of the selected biochemical markers in predicting preterm labour.
AB  - OBJECTIVE: The differential diagnosis between preterm and false labour remains
      one of the most challenging issues in perinatal medicine. AIM: To assess the
      prognostic importance of the selected biochemical markers in predicting preterm
      labour. MATERIAL AND METHODS: 74 patients hospitalized due to threatening preterm
      labour. 51 women gave birth prematurely; the remaining 23 were diagnosed with
      false labour. We used ELISA arrays to study 13 proteins: IGFBP-1, IGFBP-2, BDNF,
      L-Selectin, E-Selectin, ICAM-1, PECAM, VCAM-1, MIP-1 delta (MIP-1d) MIP-3beta
      (MIP-3b), Eotaxin-1, Eotaxin-2, BLC. RESULTS: An increased risk of preterm labour
      should be expected when the serum concentration for: IGFBP-1 > 158.83 pg/ml
      (sens. 0.608, sp. 0.609, p < 0.0001); MIP-1d < 27.66 pg/ml (sens. 0.627, sp.
      0.627, p = 0.021); BDNF >36.54 pg/ml (sens. 0.630, sp. 0.647, p = 0.002); BLC
      >25.46 pg/ml (sens. 0.588, sp. 0.609, p < 0.001); Eotaxin-1 >1.16 pg/ml (sens.
      0.633, sp. 0.652). CONCLUSION: There have been reported statistically significant
      differences in serum concentrations of selected proteins in women with preterm
      labour and false labour.

PMID- 22646707
TI  - Gluten-free foods and the cost of prescriptions.

PMID- 22646706
TI  - Effects of yeast trehalose-6-phosphate synthase 1 on gene expression and
      carbohydrate contents of potato leaves under drought stress conditions.
AB  - BACKGROUND: The development of drought-tolerant, elite varieties of potato
      (Solanum tuberosum L.) is a challenging task, which might be achieved by
      introducing transgenic lines into breeding. We previously demonstrated that
      strains of the White Lady potato cultivar that express the yeast trehalose-6
      phosphate synthase (TPS1) gene exhibit improved drought tolerance. RESULTS: We
      investigated the responses of the drought-sensitive potato cultivar White Lady
      and the drought-tolerant TPS1 transgenic variant to prolonged drought stress at
      both the transcriptional and metabolic levels. Leaf mRNA expression profiles were
      compared using the POCI microarray, which contains 42,034 potato unigene probes.
      We identified 379 genes of known function that showed at least a 2-fold change in
      expression across genotypes, stress levels or the interaction between these
      factors. Wild-type leaves had twice as many genes with altered expression in
      response to stress than TPS1 transgenic leaves, but 112 genes were differentially
      expressed in both strains. We identified 42 transcription factor genes with
      altered expression, of which four were uniquely up-regulated in TPS1 transgenic
      leaves. The majority of the genes with altered expression that have been
      implicated in photosynthesis and carbohydrate metabolism were down-regulated in
      both the wild-type and TPS1 transgenic plants. In agreement with this finding,
      the starch concentration of the stressed leaves was very low. At the metabolic
      level, the contents of fructose, galactose and glucose were increased and
      decreased in the wild-type and TPS1 transgenic leaves, respectively, while the
      amounts of proline, inositol and raffinose were highly increased in both the wild
      type and TPS1 transgenic leaves under drought conditions. CONCLUSIONS: To our
      knowledge, this study is the most extensive transcriptional and metabolic
      analysis of a transgenic, drought-tolerant potato line. We identified four genes
      that were previously reported as drought-responsive in non-transgenic Andean
      potato cultivars. The substantial increases in proline, inositol and raffinose
      contents detected in both the wild-type and TPS1 transgenic leaves appears to be
      a general response of potatoes to drought stress. The four transcription factors
      uniquely up-regulated in TPS1 transgenic leaves are good candidates for future
      functional analyses aimed at understanding the regulation of the 57 genes with
      differential expression in TPS1 transgenic leaves.

PMID- 22646708
TI  - N,N-Diarylammonium pyrosulfate as a highly effective reverse micelle-type
      catalyst for hydrolysis of esters.
AB  - Reverse micelle-type N,N-diarylammonium pyrosulfate (3-5 mol %) efficiently
      catalyzes the hydrolysis of esters (up to 100 mmol scale) under organic solvent
      free conditions. The present method is successfully applied to the hydrolysis of
      various esters without the decomposition of the base-sensitive moieties and
      without any loss of optical purity for alpha-heterosubstituted carboxylic acids.

PMID- 22646709
TI  - Sympathetic ophthalmia after proton beam irradiation for choroidal melanoma.
AB  - PURPOSE: To determine the incidence and to discuss pathogenic mechanisms of
      sympathetic ophthalmia in patients treated for choroidal melanoma. DESIGN:
      Retrospective. METHODS: We analyzed the clinical and pathological data of 4867
      patients, treated for choroidal melanoma at Institute Curie-Orsay, between 1998
      and 2011. Were involved patients with uveitis of the adelphe eye filling clinical
      and angiographic criteria of sympathetic ophthalmia. Extensive work-up was
      undertaken to rule out another etiology of the inflammation. RESULTS: Three
      patients developed sympathetic ophthalmia respectively 7, 4 and 3 years after
      protontherapy.The incidence of this complication was 6.1 per 10000 patients
      treated by proton beam radiation. Ocular perforating injury was ruled out and
      radioactive effect of treatment was incriminated in the occurrence of sympathetic
      ophthalmia. CONCLUSION: Sympathetic ophthalmia remains a rare complication which
      must be treated promptly and aggressively to prevent blindness.Proton beam
      irradiation could induce disruption of uveal tissue which enhances auto immune
      reactions.

PMID- 22646710
TI  - Effects of sleep apnea syndrome on delayed memory and executive function in
      elderly adults.
AB  - OBJECTIVES: To identify differences in cognitive function between elderly adults
      with sleep apnea syndrome (SAS) and healthy controls. DESIGN: Cross-sectional.
      SETTING: Sleep laboratory at Seoul National University Bundang Hospital.
      PARTICIPANTS: Sixty-three elderly adults (26 female; mean age 68.2 +/- 4.8)
      without cognitive disorders. MEASUREMENTS: Sleep-laboratory polysomnography
      findings and cognitive function results determined using the Korean version of
      the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological
      Assessment Battery. RESULTS: When the control group (apnea-hypopnea index (AHI) <
      15) was compared with the groups with mild to moderate (15 <= AHI < 30) and
      severe (AHI >= 30) SAS, significant differences in delayed recall (P = .003) and
      errors on the Trail-Making Test Part B (TMT B; P = .009) were observed, with
      participants with severe SAS showing greater impairment on both tests than
      controls (P = .02 and P = .01, respectively). Stepwise multiple regression showed
      that oxygen desaturation index (beta = -0.37, P = .003) and educational level
      (beta = 0.24, P = .04) determined delayed recall impairment (adjusted coefficient
      of determination (R (2)) = 17.8%, P = .003). TMT B errors were independently
      associated with educational level (beta = -0.41, P = .001) and AHI (beta = 0.31,
      P = .007; adjusted R (2) = 25.7%, P = .001). CONCLUSION: Severe SAS is associated
      with measures of delayed recall and executive function in cognitively healthy
      older adults. Although further study is needed, this evidence may provide further
      rationale for the treatment of SAS in older adults. Moreover, the role of SAS as
      a risk factor for cognitive disorders needs to be determined.

PMID- 22646711
TI  - Anal skin tags: removal made simple.
AB  - AIM: Anal skin tags are a common finding. They are found in one-third of patients
      with bening anal disorders. We describe a simple method of anal skin tag removal
      during stapled anopexy. This involves utilizing the circular anal dilator
      provided with the stapling kit. METHOD: Skin tags are brought through the
      perforations of the circular anal dilator of the stapling kit. The skin tags are
      removed by cautery. RESULTS: Minimal pain has been noticed in patients under
      going this procedure. CONCLUSION: Anal skin tags can be removed in a simple
      manner using components provided with the stapling kit. We decribe a simple
      method of anal skin tag removal during stapled anopexy. This involves utilizing
      the circular anal dilator provided with the stapling kit.

PMID- 22646712
TI  - Mean platelet volume: an important predictor of coronary collateral development.
AB  - Collaterals, which develop in response to ischemic stimuli derived from coronary
      artery disease (CAD), contribute to reduction of infarct size, left ventricular
      dysfunction, and mortality. However, there is considerable variation among
      patients with coronary heart disease regarding the extent of coronary collateral
      development (CCD). In this study, we aimed to investigate the association of the
      degree of platelet activation via mean platelet volume (MPV) with coronary
      collateral circulation. Therefore, 210 patients who underwent coronary
      angiography and had coronary stenosis >=50 % in at least one coronary artery were
      included in the study. Clinical information and analyses of blood samples were
      obtained from a review of the patients' chart. Blood samples for MPV were
      analyzed by K3 EDTA and collateral vessels were graded according to the Rentrop
      classification. In the study group, 150 of the 210 patients were found to have
      inadequate CCD. Although there was no difference between the two groups with
      regard to platelet count, MPV levels were significantly higher in the patients
      who had inadequate CCD (11.3 +/- 1.0 fl vs. 9.5 +/- 1.5 fl, p < 0.001).
      Furthermore, the Gensini score was significantly lower in patients who had
      inadequate CCD (45 +/- 46 vs. 91 +/- 35, p < 0.001). MPV, Gensini score, age,
      female gender, total cholesterol, red cell distribution width, triglyceride, and
      fasting glucose levels were found to have univariate association with poor CCD.
      In multivariate logistic regression model, MPV (OR = 2.45, p < 0.001) and Gensini
      score (OR = 0.98, p < 0.001) were found to be the independent predictors of
      impaired CCD. In receiver operator characteristic curve analysis, optimal cut-off
      value of MPV to predict inadequate CCD was found as >9.6 fl, with 96% sensitivity
      and 84.7% positive predictive value. In conclusion, we can say that MPV is an
      important, simple, effortless, and cost effective tool and can be useful in
      predicting the CCD in patients with significant CAD.

PMID- 22646713
TI  - Suicide by cop in film and society: dangerousness, depression, and justice.
AB  - Provoking police officers to kill oneself or "suicide by cop" (SBC) has received
      scholarly as well as public attention. The extent to which film representations
      of SBC reflect SBC in society in relation to danger, depression, and other
      features was assessed in this study. Data on cinematic portrayals of SBC are from
      16 American films; corresponding data on SBC in the real world are taken from 19
      empirical studies. While the demographic features of SBC in the real world are
      largely reflected in film, major differences exist on motivations and incident
      characteristics. Motives for cinematic SBC were unlike SBC in society, wherein,
      respectively, 0% vs. 35% had attempted suicide in the past, 6% vs. 47% were
      chronically depressed, and 77% vs. 7% had recently killed someone. Cinematic SBC
      events disproportionately involve murderous, dangerous persons who are not
      depressed, and their deaths convey a sense of justice. While such media
      distortions can be profitable and entertain the audience, they also contribute to
      public misunderstandings of the nature of deviance and hinder the development of
      effective suicide and violence prevention programs.

PMID- 22646714
TI  - Contrasting medical models of alcohol problems in Victoria around 1900.
AB  - AIMS: This paper examines four specialist medical inebriety institutions in
      Victoria, Australia between 1870 and 1930, which positioned themselves in
      distinct ways. It analyses how the treatment in each institution was located
      within wider medical approaches and contemporary medical ideas and practice.
      METHODS: Medical journals and texts, newspaper articles, government reports and
      institutional archives are used in the analysis. FINDINGS AND CONCLUSIONS:
      Alcohol treatment institutions in the late 19th and early 20th centuries were of
      several types, differentiated according to treatment approaches and their
      underlying premises as to the nature of the disease being treated, the particular
      patient groups for which they catered and their funding models and capacity to
      take patients committed for treatment under legislation. The institutional types
      identified in other Anglophone countries in this period can be extended to
      Australia, with some local variations in the timing of the appearance of the
      models, the longevity of institutions and gender of patients. In Australia there
      was no tradition of mutual patient support, as seen at the time in the United
      States. Each institution represented itself differently, in particular in terms
      of its particular medical model, although the treatments in practice differed
      less than in theory. The models employed allowed each institution to position
      itself in relation to trends in medical theory and practice, in particular to
      different conceptualizations of the type of disease being treated. Evaluating
      treatment models for alcohol problems in terms of medical theory and practice of
      the time can explain contrasting approaches.

PMID- 22646715
TI  - The role of mesenchymal stem cells in veterinary therapeutics - a review.
AB  - Adult mammalian tissue contains a population of cells known as mesenchymal stem
      cells (MSC), that possess the capability to secrete regenerative cytokines and to
      differentiate into specialised cell types. When transplanted to a site of injury
      MSC embed in damaged tissue and repair and regenerate the tissue by secreting
      cytokines. The immuno-privileged and immuno-regulatory capabilities of MSC
      enhance their therapeutic potential not only in autologous but also allogeneic
      recipients. Studies have demonstrated the beneficial effects of MSC in the
      treatment of a variety of clinical conditions including osteoarthritis, tendon
      injuries, and atopic dermatitis in domestic animals. Studies using animal models
      have shown promising results following MSC or MSC secretion therapy for induced
      injury in musculoskeletal and nervous systems and some organ diseases. This
      review describes the stem cell types relevant to regenerative medicine and the
      procedures used for isolation, identification, expansion, enrichment and
      differentiation of these cells. We also review the use of MSC in animal models of
      disease as well as diseases in the clinical veterinary setting.

PMID- 22646718
TI  - Comparative proteomic analysis of mushroom cell wall proteins among the different
      developmental stages of Pleurotus tuber-regium.
AB  - Cell wall proteins (CWPs) play a vital role in the development of the different
      morphological stages including mycelium, fruiting body, and sclerotium in
      mushrooms which are important human food sources. Using fractionation by
      detergents and reducing agents, mushroom cell wall fractions from the different
      developmental stages of Pleurotus tuber-regium (PTR) were prepared. Using one
      dimensional gel electrophoresis coupled with LC-MS, there were 103, 91, and 48
      noncovalently linked CWPs identified in the cell wall fractions of the PTR
      mycelium, fruiting body, and sclerotium, respectively. Comparing the CWPs in
      these cell wall fractions, 19 of them were in common, among which 17 belonged to
      the functional categories of translation, ribosomal structure, and biogenesis.
      This is the first study to provide important biochemical insights into the
      different developmental stages of PTR mediated by CWPs, and the identified CWPs
      helped to explain the morphological changes of PTR mushrooms during cultivation.

PMID- 22646717
TI  - Effects on human transcriptome of mutated BRCA1 BRCT domain: a microarray study.
AB  - BACKGROUND: BRCA1 (breast cancer 1, early onset) missense mutations have been
      detected in familial breast and ovarian cancers, but the role of these variants
      in cancer predisposition is often difficult to ascertain. In this work, the
      molecular mechanisms affected in human cells by two BRCA1 missense variants,
      M1775R and A1789T, both located in the second BRCT (BRCA1 C Terminus) domain,
      have been investigated. Both these variants were isolated from familial breast
      cancer patients and the study of their effect on yeast cell transcriptome has
      previously provided interesting clues to their possible role in the pathogenesis
      of breast cancer. METHODS: We compared by Human Whole Genome Microarrays the
      expression profiles of HeLa cells transfected with one or the other variant and
      HeLa cells transfected with BRCA1 wild-type. Microarray data analysis was
      performed by three comparisons: M1775R versus wild-type (M1775RvsWT-contrast),
      A1789T versus wild-type (A1789TvsWT-contrast) and the mutated BRCT domain versus
      wild-type (MutvsWT-contrast), considering the two variants as a single mutation
      of BRCT domain. RESULTS: 201 differentially expressed genes were found in
      M1775RvsWT-contrast, 313 in A1789TvsWT-contrast and 173 in MutvsWT-contrast. Most
      of these genes mapped in pathways deregulated in cancer, such as cell cycle
      progression and DNA damage response and repair. CONCLUSIONS: Our results
      represent the first molecular evidence of the pathogenetic role of M1775R,
      already proposed by functional studies, and give support to a similar role for
      A1789T that we first hypothesized based on the yeast cell experiments. This is in
      line with the very recently suggested role of BRCT domain as the main effector of
      BRCA1 tumor suppressor activity.

PMID- 22646719
TI  - Single cell oil of oleaginous fungi from the tropical mangrove wetlands as a
      potential feedstock for biodiesel.
AB  - BACKGROUND: Single cell oils (SCOs) accumulated by oleaginous fungi have emerged
      as a potential alternative feedstock for biodiesel production. Though fungi from
      mangrove ecosystem have been reported for production of several lignocellulolytic
      enzymes, they remain unexplored for their SCO producing ability. Thus, these
      oleaginous fungi from the mangrove ecosystem could be suitable candidates for
      production of SCOs from lignocellulosic biomass. The accumulation of lipids being
      species specific, strain selection is critical and therefore, it is of importance
      to evaluate the fungal diversity of mangrove wetlands. The whole cells of these
      fungi were investigated with respect to oleaginicity, cell mass, lipid content,
      fatty acid methyl ester profiles and physicochemical properties of
      transesterified SCOs in order to explore their potential for biodiesel
      production. RESULTS: In the present study, 14 yeasts and filamentous fungi were
      isolated from the detritus based mangrove wetlands along the Indian west coast.
      Nile red staining revealed that lipid bodies were present in 5 of the 14 fungal
      isolates. Lipid extraction showed that these fungi were able to accumulate > 20%
      (w/w) of their dry cell mass (4.14 - 6.44 g L-1) as lipids with neutral lipid as
      the major fraction. The profile of transesterified SCOs revealed a high content
      of saturated and monounsaturated fatty acids i.e., palmitic (C16:0), stearic
      (C18:0) and oleic (C18:1) acids similar to conventional vegetable oils used for
      biodiesel production. The experimentally determined and predicted biodiesel
      properties for 3 fungal isolates correlated well with the specified standards.
      Isolate IBB M1, with the highest SCO yield and containing high amounts of
      saturated and monounsaturated fatty acid was identified as Aspergillus terreus
      using morphotaxonomic study and 18 S rRNA gene sequencing. Batch flask cultures
      with varying initial glucose concentration revealed that maximal cell biomass and
      lipid content were obtained at 30gL-1. The strain was able to utilize cheap
      renewable substrates viz., sugarcane bagasse, grape stalk, groundnut shells and
      cheese whey for SCO production. CONCLUSION: Our study suggests that SCOs of
      oleaginous fungi from the mangrove wetlands of the Indian west coast could be
      used as a potential feedstock for biodiesel production with Aspergillus terreus
      IBB M1 as a promising candidate.

PMID- 22646720
TI  - Right frontal cortical asymmetry predicts empathic reactions: support for a link
      between withdrawal motivation and empathy.
AB  - Depression, diminished positive affect, and exaggerated negative affect have all
      been linked to right frontal cortical asymmetry as measured by
      electroencephalography (EEG). Emerging evidence, however, suggests that right
      frontal EEG asymmetry might be linked to empathic responding. EEG was used to
      assess baseline asymmetries in frontal brain activity. Participants viewed images
      associated with a charity and then rated their sadness, personal distress,
      perspective-taking, and empathic concern towards the images. We found that
      baseline measures of right frontal asymmetry were a significant predictor of
      empathic concern, a relationship that was mediated by feelings of sadness. These
      results provide a more complex view of right frontal asymmetry and suggest that
      this pattern of brain activity might facilitate sensitivity towards the suffering
      of others.

PMID- 22646721
TI  - Depositional ice nucleation on monocarboxylic acids: effect of the O:C ratio.
AB  - The heterogeneous ice nucleation efficiency of a series of thin C3-C6
      monocarboxylic acid films between 180 and 200 K has been investigated using a
      Knudsen cell flow reactor. At each temperature, the critical ice saturation ratio
      for depositional nucleation as well as the effective contact angle was found to
      be strongly dependent on the chemical nature of the film. For the organic acids
      used in this study, increasing the O:C ratio lowered the supersaturation required
      for the onset of heterogeneous ice nucleation and decreased the effective angle
      of contact. This could be the result of an increase in surface hydrophilicity,
      which allows the film to better adsorb a metastable, icelike layer of water that
      serves as a template for the new phase of ice. These ice nucleation results are
      in excellent agreement with ice nucleation on laboratory generated alpha-pinene
      secondary organic aerosol as well as on predominantly organic particles collected
      in Mexico City.

PMID- 22646722
TI  - Study of vancomycin resistance in faecal enterococci from healthy humans and dogs
      in Spain a decade after the avoparcin ban in Europe.
AB  - One hundred and 26 faecal samples from healthy dogs (2009) and 157 faecal samples
      from healthy humans (2007) from La Rioja region (Spain) were tested to know the
      carriage of vancomycin-resistant enterococci (VRE). VRE with intrinsic resistance
      (vanC) were found in 12% of healthy dogs and humans (29 Enterococcus gallinarum
      and four Enterococcus casseliflavus). Nevertheless, VRE with acquired mechanism
      of resistance were not detected among these samples. Four Enterococcus faecalis
      isolates with vancomycin MIC of 8-16 mg L(-1) were recovered in human samples,
      but no single organism with known mechanism of acquired resistance could be
      identified. These 37 VRE isolates (33 E. gallinarum/E. casseliflavus and four E.
      faecalis) of dog and human origin were further characterized (PCR detection of
      antibiotic resistance, virulence and bacteriocin genes). High prevalence of
      tetracycline resistance was identified (70%), especially among dog isolates
      harbouring tet(M) +/- tet(L) genes; erythromycin resistance was also higher among
      isolates from dogs and they harboured the erm(B) gene, associated with erm(A)
      gene in one case. Virulence genes were only identified among E. faecalis isolates
      of human origin (agg, cpd and/or gelE) and never among E. gallinarum/E.
      casseliflavus of human or dog origin. Five E. gallinarum isolates of dog and
      three E. faecalis of human origin expressed bacteriocin activity; among them,
      only one E. faecalis presented activity against Listeria monocytogenes. The
      bacteriocin structural gene ef1097 was identified in 3 bacteriocin-producing E.
      faecalis isolates, associated with ent1071 in one of them.

PMID- 22646723
TI  - Clinical, dermoscopic and histopathologic features of genital and extragenital
      lichen sclerosus.
AB  - BACKGROUND: Little is currently known about the dermoscopic patterns of genital
      and extragenital lichen sclerosus (LS). In order to evaluate and compare the
      dermoscopic and histopathologic patterns of genital and extragenital lichen
      sclerosus, a retrospective analysis of clinical, dermoscopic and histopathologic
      features of genital and extragenital LS, collected between March 2010 and
      December 2011 at four dermatology clinics in Greece, Italy, Serbia and Uruguay
      was performed. OBSERVATIONS: A total of 29 lesions from 14 (mean age 62.8 years)
      and 12 (mean age 53.5 years) patients with genital and extragenital LS,
      respectively were analyzed. Mean duration of disease was 3.5 years for genital
      and 1.8 years for extragenital LS. White-yellowish structureless areas were seen
      in all cases of genital and extragenital LS; however linear vessels occurred at
      higher frequency in genital than in extragenital lesions (85.7% vs. 33.3%,
      respectively). Extragenital LS revealed two different time-related patterns:
      keratotic plugs were more prevalent in lesions with short duration (<2 years),
      whereas longer persisting lesions appeared atrophic and revealed fine chrysalis
      structures. CONCLUSIONS: Our morphologic study provides novel insights into the
      morphologic diversity of LS at different body sites and different stages of
      progression.

PMID- 22646724
TI  - A genomic overview of short genetic variations in a basal chordate, Ciona
      intestinalis.
AB  - BACKGROUND: Although the Ciona intestinalis genome contains many allelic
      polymorphisms, there is only limited data analyzed systematically. Establishing a
      dense map of genetic variations in C. intestinalis is necessary not only for
      linkage analysis, but also for other experimental biology including molecular
      developmental and evolutionary studies, because animals from natural populations
      are typically used for experiments. RESULTS: Here, we identified over three
      million candidate short genomic variations within a 110 Mb euchromatin region
      among five C. intestinalis individuals. The average nucleotide diversity was
      approximately 1.1%. Genetic variations were found at a similar density in
      intergenic and gene regions. Non-synonymous and nonsense nucleotide substitutions
      were found in 12,493 and 1,214 genes accounting for 81.9% and 8.0% of the entire
      gene set, respectively, and over 60% of genes in the single animal encode non
      identical proteins between maternal and paternal alleles. CONCLUSIONS: Our
      results provide a framework for studying evolution of the animal genome, as well
      as a useful resource for a wide range of C. intestinalis researchers.

PMID- 22646725
TI  - Labeling lysosomes and tracking lysosome-dependent apoptosis with a cell
      permeable activity-based probe.
AB  - In this study, we describe a new strategy for labeling and tracking lysosomes
      with a cell-permeable fluorescent activity-based probe (CpFABP) that is
      covalently bound to select lysosomal proteins. Colocalization studies that
      utilized LysoTracker probes as standard lysosomal markers demonstrated that our
      novel probe is effective in specifically labeling lysosomes in various kinds of
      live cells. Furthermore, our studies revealed that this probe has the ability to
      label fixed cells, permeabilized cells, and NH4Cl-treated cells, unlike
      LysoTracker probes, which show ineffective labeling under the same conditions.
      Remarkably, when applied to monitor the process of lysosome-dependent apoptosis,
      our probe not only displayed the expected release of lysosomal cathepsins from
      lysosomes into the cytosol but also revealed additional information about the
      location of the cathepsins during apoptosis, which is undetectable by other
      chemical lysosome markers. These results suggest a wide array of promising
      applications for our probe and provide useful guidelines for its use as a
      lysosome marker in lysosome-related studies. 

PMID- 22646729
TI  - Colorectal smartphone apps: opportunities and risks.
AB  - AIM: The increased utilization of smartphones within the clinical environment
      together with connected applications (apps) provides opportunity for doctors,
      including coloproctologists, to integrate such technology into clinical practice.
      However, the reliability of unregulated medical apps has recently been called
      into question. Here, we review contemporary medical apps specifically themed
      towards colorectal diseases and assess levels of medical professional involvement
      in their design and content. METHOD: The most popular smartphone app stores
      (iPhone, Android, Blackberry, Nokia, Windows and Samsung) were searched for
      colorectal disease themed apps, using the disease terms colorectal cancer,
      Crohn's disease, ulcerative colitis, diverticulitis, haemorrhoids, anal fissure,
      bowel incontinence and irritable bowel syndrome. RESULTS: A total of 68
      individual colorectal themed apps were identified, amongst which there were five
      duplicates. Only 29% of colorectal apps had had customer satisfaction ratings and
      32% had named medical professional involvement in their development or content.
      CONCLUSION: The benefits of apps are offset by lack of colorectal specification.
      There is little medical professional involvement in their design. Increased
      regulation is required to improve accountability of app content.

PMID- 22646728
TI  - Design, synthesis, and spectroscopic properties of extended and fused pyrrolo-dC
      and pyrrolo-C analogs.
AB  - The syntheses of four fluorescent nucleoside analogs, related to pyrrolo-C (PyC)
      and pyrrolo-dC (PydC) through the conjugation or fusion of a thiophene moiety,
      are described. A thorough photophysical analysis of the nucleosides, in
      comparison to PyC, is reported.

PMID- 22646730
TI  - Inhibition of phenylpropanoid biosynthesis increases cell wall digestibility,
      protoplast isolation, and facilitates sustained cell division in American elm
      (Ulmus americana).
AB  - BACKGROUND: Protoplast technologies offer unique opportunities for fundamental
      research and to develop novel germplasm through somatic hybridization, organelle
      transfer, protoclonal variation, and direct insertion of DNA. Applying protoplast
      technologies to develop Dutch elm disease resistant American elms (Ulmus
      americana L.) was proposed over 30 years ago, but has not been achieved. A
      primary factor restricting protoplast technology to American elm is the
      resistance of the cell walls to enzymatic degradation and a long lag phase prior
      to cell wall re-synthesis and cell division. RESULTS: This study suggests that
      resistance to enzymatic degradation in American elm was due to water soluble
      phenylpropanoids. Incubating tobacco (Nicotiana tabacum L.) leaf tissue, an
      easily digestible species, in aqueous elm extract inhibits cell wall digestion in
      a dose dependent manner. This can be mimicked by p-coumaric or ferulic acid,
      phenylpropanoids known to re-enforce cell walls. Culturing American elm tissue in
      the presence of 2-aminoindane-2-phosphonic acid (AIP; 10-150 MUM), an inhibitor
      of phenylalanine ammonia lyase (PAL), reduced flavonoid content, decreased tissue
      browning, and increased isolation rates significantly from 11.8% (+/-3.27) in
      controls to 65.3% (+/-4.60). Protoplasts isolated from callus grown in 100 MUM
      AIP developed cell walls by day 2, had a division rate of 28.5% (+/-3.59) by day
      6, and proliferated into callus by day 14. Heterokaryons were successfully
      produced using electrofusion and fused protoplasts remained viable when embedded
      in agarose. CONCLUSIONS: This study describes a novel approach of modifying
      phenylpropanoid biosynthesis to facilitate efficient protoplast isolation which
      has historically been problematic for American elm. This isolation system has
      facilitated recovery of viable protoplasts capable of rapid cell wall re
      synthesis and sustained cell division to form callus. Further, isolated
      protoplasts survived electrofusion and viable heterokaryons were produced.
      Together, these results provide the first evidence of sustained cell division,
      callus regeneration, and potential application of somatic cell fusion in American
      elm, suggesting that this source of protoplasts may be ideal for genetic
      manipulation of this species. The technological advance made with American elm in
      this study has potential implications in other woody species for fundamental and
      applied research which require availability of viable protoplasts.

PMID- 22646731
TI  - Examining a brief suicide screening tool in older adults engaging in risky
      alcohol use.
AB  - Alcohol misuse increases risk of suicidal behavior in older adults. The
      Depressive Symptom Inventory-Suicidality Subscale (DSI-SS; Metalsky & Joiner,
      1997) and its relation to suicide attempt history was examined to see if it
      differed for older adults as a function of their alcohol use. Structural equation
      modeling was used in a sample (N=1,061) of older adult outpatients to examine the
      scale's measurement invariance and population heterogeneity and its relation to
      suicide attempt history. Analyses supported the equivalence of the DSI-SS in
      risky and nonrisky drinkers. The DSI-SS significantly predicted past suicide
      attempts. Findings support the viability of the DSI-SS as suicide screening tool
      for older adults.

PMID- 22646732
TI  - Strikingly low prevalence of atrial fibrillation in elderly Tanzanians.
AB  - OBJECTIVES: To determine the prevalence of atrial fibrillation (AF) in
      individuals aged 70 and older in a rural African community. DESIGN: Community
      based cross-sectional survey. SETTING: A demographic surveillance site (DSS)
      within the rural Hai district of northern Tanzania. PARTICIPANTS: Approximately
      one-quarter (N = 2,232) of the population aged 70 and older of the DSS.
      MEASUREMENTS: Participants were screened for AF using 12-lead
      electrocardiography; demographic and 1-year mortality data were collected; and
      functional status, body mass index, and blood pressure were recorded. The sex
      specific prevalence of AF in each 5-year age band was determined. RESULTS:
      Fifteen of 2,232 participants (12 women, 3 men) had AF, giving a crude prevalence
      rate of 0.67% (95% confidence interval (CI) = 0.33-1.01) and an age-adjusted
      prevalence of 0.64% (95% CI = 0.31-0.97). Prevalence was 0.96% (95% CI = 0.42
      1.49) in women and 0.31% (95% CI = -0.04 to 1.24) in men. Prevalence increased
      with age, from 0.46% (95% CI = 0.01-0.90) in those aged 70-74-1.30% (95% CI =
      0.17-2.42) in those aged 85 and older. One-year mortality was 50% in women and
      66.6% in men. CONCLUSIONS: This is the first published community-based AF
      prevalence study from sub-Saharan Africa. The prevalence rate of AF is strikingly
      lower than in other elderly populations studied, yet the 1-year mortality rate
      was exceedingly high.

PMID- 22646733
TI  - Relationships between leisure factors and health-related stress among older
      adults.
AB  - This study examined the relationships between leisure autonomy, leisure
      competence, and leisure social support and health-related stress among older
      adults. It also examined whether an increase in age moderated the relationships
      between these three leisure factors and health-related stress. Two hundred fifty
      six older adults living in Keelung City, Taiwan were randomly selected as
      participants at the first year. At the second year, 195 of them continued to
      respond to the questionnaire of the study that included leisure autonomy, leisure
      competence, leisure social support, and health-related stress scales. The
      questionnaire data were analyzed using a regression analysis. The results of this
      analysis showed that leisure autonomy, leisure competence, and leisure social
      support were significantly negatively related to health-related stress and that
      an increase in age moderated the relationship between leisure competence and
      health-related stress. Implications of the results are discussed.

PMID- 22646734
TI  - Role of plasma EBV DNA levels in predicting recurrence of nasopharyngeal
      carcinoma in a Western population.
AB  - BACKGROUND: Loco-regionally advanced nasopharyngeal carcinomas can be cured by
      the combination of chemotherapy and radiotherapy. In Eastern countries, plasma
      levels of viral Epstein-Barr deoxyribonucleic acid (DNA) are accurate in
      predicting recurrence, but few data are available in Western populations. The aim
      of this prospective study was to evaluate the relationship between viral Epstein
      Barr DNA copy numbers in plasma and the response rate, progression-free survival
      and overall survival in a cohort of Western patients with stage IIb-IVb
      nasopharyngeal cancer. METHODS: We evaluated plasma samples from 36 consecutive
      patients treated with induction chemotherapy followed by chemoradiation. EBV copy
      numbers were determined after DNA extraction using real-time quantitative
      polymerase chain reaction. Survival curves were estimated using the Kaplan-Meier
      method. RESULTS: Circulating Epstein-Barr virus DNA levels were measured before
      treatment, at the end of concomitant chemo- and radiotherapy, and during the
      follow-up period. Pre-treatment levels significantly correlated with the initial
      stage and probability of relapse. Their increase was 100% specific and 71.3%
      sensitive in detecting loco-regional or metastatic recurrence (an overall
      accuracy of 94.4%). Three-year progression-free and overall survival were
      respectively 78.2% and 97.1%. CONCLUSIONS: The results of this study confirm that
      patients from a Western country affected by loco-regionally advanced
      nasopharyngeal carcinoma have high plasma Epstein-Barr virus DNA levels at
      diagnosis. The monitoring of plasma levels is sensitive and highly specific in
      detecting disease recurrence and metastases.

PMID- 22646735
TI  - Extracts from Trifolium pallidum and Trifolium scabrum aerial parts as modulators
      of blood platelet adhesion and aggregation.
AB  - A growing number of reports indicate that some species of clover (Trifolium) may
      have remarkable medical importance; however, the effects of these plants on blood
      platelets and hemostasis are inadequately recognized. This work was designed to
      study the effects of Trifolium pallidum and Trifolium scabrum extracts on the
      functions of human blood platelets in vitro. Platelet suspensions were
      preincubated with extracts from aerial parts of T. pallidum (phenolic fraction
      and clovamide fraction) and T. scabrum (phenolic fraction) at the final
      concentrations of 12.5, 25, and 50 ug/ml. Then, for platelet activation thrombin
      (0.1 U/ml), thrombin receptor activating peptide (TRAP; 20 uM), or adenosine
      diphosphate (ADP; 1 uM) were used. The effects of Trifolium extracts on adhesion
      of blood platelets to fibrinogen and collagen were determined by enzyme-linked
      immunosorbent assay (ELISA) method. Platelet aggregation was monitored on a dual
      channel Chronolog aggregometer. In these studies, we also compared the action of
      tested plant extracts with the effects of another antiplatelet plant-derived
      compound - resveratrol (3,4',5-trihydroxystilbene). The performed assays
      demonstrated that the tested extracts might influence the platelet functions in
      vitro. The inhibitory, concentration-dependent effects of all tested extracts on
      adhesion of thrombin-stimulated platelets to collagen was found. Both extracts
      from T. pallidum and from T. scabrum reduced the thrombin-induced platelet
      adhesion to fibrinogen. Furthermore, in the presence of all three extracts, the
      platelet aggregation induced by thrombin was slightly inhibited. Our results also
      indicate that the tested plant extracts (at the highest concentrations used of 50
      ug/ml), similar to purified resveratrol, inhibit selected steps of platelet
      activation stimulated by both proteolytic (thrombin) and nonproteolytic agonists
      (TRAP or ADP). In the comparative studies, T. pallidum and T. scabrum extracts
      was not found to be more effective antiaggregatory factor, than resveratrol.
      Extracts from T. pallidum and T. scabrum aerial parts reveal antiplatelet
      properties: the antiadhesive effect was similar to that of the reference compound
      resveratrol, whereas the antiaggregant effect was less marked. The results
      obtained suggest that these plants may be a promising source of natural
      compounds, valuable in the prevention of the enhanced activity of blood platelets
      in numerous cardiovascular diseases, observed in menopausal or postmenopausal
      women.

PMID- 22646736
TI  - Reliability and validity of the Functional Assessment of Human Immunodeficiency
      Virus Infection (FAHI) in patients with drug and alcohol use disorders.
AB  - Human Immunodeficiency Virus (HIV) and substance use disorders can both
      significantly impact a patient's quality of life (QOL), and it is, therefore,
      important to assess QOL throughout treatments for these chronic conditions. This
      study evaluated the psychometric properties of the Functional Assessment of Human
      Immunodeficiency Virus Infection (FAHI) in 170 HIV-positive patients who
      participated in a substance abuse treatment study. Internal consistency of the
      FAHI was good. Convergent and discriminant validity were generally supported with
      comparisons to other patient-reported measures. FAHI scores were not
      significantly associated with viral loads or CD4 counts, and they were similar in
      patients with and without AIDS. Patients who achieved longer durations of drug
      and alcohol abstinence during treatment reported better QOL post-treatment. The
      FAHI appears to be a reliable and valid measure for assessing QOL in HIV-positive
      patients with concurrent drug and alcohol use disorders.

PMID- 22646738
TI  - Minding our methods: how choice of time series, reference dates, and statistical
      approach can influence the representation of temperature change.

PMID- 22646739
TI  - Blindness in a pulseless young woman: lessons learned.
AB  - PURPOSE: To report a young woman who presented with blindness secondary to ocular
      ischemic syndrome (OIS) as the initial presenting feature of Takayasu arteritis
      (TA). DESIGN: Case report. METHODS: Computer tomography (CT) aortogram showed
      severely stenosed aortic branches. Fundus fluorescein angiography showed diffuse
      capillary nonperfusion. RESULTS: With conventional medical therapy of initial
      pulse of intravenous methylprednisolone followed by oral steroids and
      methotrexate, her headache, fatigued feeling, and inflammatory markers improved.
      However, the visual recovery remained poor. CONCLUSIONS: OIS in TA may present
      subacutely and the visual outcome can be poor despite aggressive
      immunosuppressive therapy.

PMID- 22646737
TI  - KCa 3.1 channels maintain endothelium-dependent vasodilatation in isolated
      perfused kidneys of spontaneously hypertensive rats after chronic inhibition of
      NOS.
AB  - BACKGROUND AND PURPOSE: The purpose of the study was to investigate renal
      endothelium-dependent vasodilatation in a model of severe hypertension associated
      with kidney injury. EXPERIMENTAL APPROACH: Changes in perfusion pressure were
      measured in isolated, perfused kidneys taken from 18-week-old Wistar-Kyoto rat
      (WKY), spontaneously hypertensive rats (SHR) and SHR treated for 2 weeks with
      N(omega) -nitro-L-arginine methyl ester in the drinking water (L-NAME-treated
      SHR, 6 mg.kg(-1) .day(-1) ). KEY RESULTS: Acetylcholine caused similar dose
      dependent renal dilatation in the three groups. In vitro administration of
      indomethacin did not alter the vasodilatation, while the addition of N(w) -nitro
      L-arginine (L-NA) produced a differential inhibition of the vasodilatation,
      (inhibition in WKY > SHR > L-NAME-treated SHR). Further addition of ODQ, an
      inhibitor of soluble guanylyl cyclase, abolished the responses to sodium
      nitroprusside but did not affect the vasodilatation to acetylcholine. However,
      the addition of TRAM-34 (or charybdotoxin) inhibitors of Ca(2+) -activated K(+)
      channels of intermediate conductance (K(Ca) 3.1), blocked the vasodilatation to
      acetylcholine, while apamin, an inhibitor of Ca(2+) -activated K(+) channels of
      small conductance (K(Ca) 2.3), was ineffective. Dilatation induced by an opener
      of K(Ca) 3.1/K(Ca) 2.3 channels, NS-309, was also blocked by TRAM-34, but not by
      apamin. The magnitude and duration of NS-309-induced vasodilatation and the renal
      expression of mRNA for K(Ca) 3.1, but not K(Ca) 2.3, channels followed the same
      ranking order (WKY < SHR < L-NAME-treated SHR). CONCLUSIONS AND IMPLICATIONS: In
      SHR kidneys, an EDHF-mediated response, involving activation of K(Ca) 3.1
      channels, contributed to the mechanism of endothelium-dependent vasodilatation.
      In kidneys from L-NAME-treated SHR, up-regulation of this pathway fully
      compensated for the decrease in NO availability.

PMID- 22646740
TI  - Arthrotomy for the treatment of chronic purulent septic gonitis with subchondral
      osteolysis in two calves.
AB  - CASE HISTORY: A 6-week-old German Holstein heifer calf (Case 1) and a 4-week-old
      Charolais bull calf (Case 2) were referred because of unilateral hind limb
      lameness. Both had been treated with systemic antibiotics by the referring
      veterinarian. CLINICAL FINDINGS AND DIAGNOSIS: Based on the results of clinical,
      radiographic and ultrasonographic examination, a diagnosis of chronic purulent
      septic gonitis with subchondral osteolysis of the lateral femoral condyle was
      made in both calves. In Case 2 the lateral tibial condyle also showed osteolysis.
      TREATMENT AND OUTCOME: Treatment consisted of arthrotomy with debridement of
      abnormal bone and cartilage via a craniolateral and a caudolateral approach. Case
      1 was discharged from with grade 1/5 lameness 60 days after surgery. In a follow
      up 15 months postoperatively, the owner reported that it had been bred at 14
      months, was not lame and the affected stifle joint appeared normal. Case 2 had
      grade 2/5 lameness 52 days after surgery, but was sound at the time of slaughter
      at 22 months of age. CLINICAL RELEVANCE: Arthrotomy via a caudolateral approach
      is a suitable method for the treatment of septic purulent gonitis with osteolysis
      of the lateral femoral and tibial condyles in calves. In these cases, this
      treatment resulted in the elimination of localised inflammation, prevented
      clinically relevant spread of infection to other organs, and restored normal
      joint function.

PMID- 22646741
TI  - A systematic review of the role of adjuvant and neoadjuvant pharmacotherapy in
      patients undergoing radical prostatectomy.
AB  - INTRODUCTION: Between 25 and 30% of patients with newly diagnosed prostate cancer
      are classified as high risk for an adverse prognosis. A significant number of
      these will progress to biochemical or clinical relapse. As there is no consensus
      regarding the optimal treatment of these cases, a multimodal therapeutic
      approach, including radical prostatectomy, remains an option. AREAS COVERED: The
      Pubmed/Medline database was searched to identify trials that have evaluated
      adjuvant and neoadjuvant pharmaceutical protocols combined with radical
      prostatectomy and provided information regarding efficacy and safety. EXPERT
      OPINION: Improvements in adverse pathological findings, following operations in
      patients who received neoadjuvant treatment, have been reported in the majority
      of the reviewed studies. Furthermore, the addition of pharmacotherapy to radical
      prostatectomy has produced beneficial results in survival surrogates. However, no
      benefits in overall survival were observed with adjuvant or neoadjuvant protocols
      and toxicity was a concern, especially in combination regimens. New studies on
      the effects of current pharmacotherapy and of new agents on overall survival and
      quality of life, after defining well-established criteria for patient
      stratification and inclusion, are required urgently.

PMID- 22646742
TI  - Terahertz spectroscopy of the explosive taggant 2,3-dimethyl-2,3-dinitrobutane.
AB  - The terahertz spectrum of the crystalline explosive taggant 2,3-dimethyl-2,3
      dinitrobutane (C(6)H(12)N(2)O(4)) has been investigated as an alternative means
      of detecting solid-state explosives. The room-temperature spectrum exhibits two
      broad absorption features centered at 38.3 and 49.2 cm(-1). Once the sample is
      cooled to liquid-nitrogen temperatures, the resolution of three additional peaks
      occurs, with absorption maxima now appearing at 40.1, 47.5, 56.6, 63.9, and 73.6
      cm(-1). Solid-state density functional theory simulations, both with and without
      London force dispersion corrections, have been used for the assignment of the
      experimental cryogenic THz spectrum to specific molecular motions in the
      crystalline solid. The B3LYP hybrid density functional paired with the 6
      311G(2d,2p) basis set provides an excellent reproduction of the experimental data
      revealing that the THz spectrum arises from a mixture of intramolecular torsional
      vibrations localized primarily in the nitro groups and intermolecular lattice
      vibrations composed of rigid molecular rotations.

PMID- 22646743
TI  - A medical staff peer review system in a public teaching hospital--an internal
      quality improvement tool.
AB  - Peer review of the quality of care of the medical staff in a healthcare delivery
      system, properly executed and utilized, can bring about changes that improve the
      quality and safety of patient care, enhance clinical performance, and augment
      physician education. Although all healthcare facilities are mandated to conduct
      peer reviews, the process of how it is conducted, reported, and utilized varies
      widely. In 2007, our institution, a large public teaching acute care facility,
      developed and implemented an electronic Medical Staff Peer Review System (MS-PRS)
      that replaced the existing paper-based system and created a centralized database
      for all peer review activities. Despite limited resources and mounting known
      challenges, we have developed and implemented a system that includes 100%
      mortality reviews, an ongoing random review for reappointment and operative
      procedures, and morbidity peer reviews. Parallel to the 4-year implementation of
      the system, we observed a steady, significant downward trend in the medical
      malpractice claim rate, which can be attributable in part to the implementation
      of MS-PRS. In this paper, we share our experiences in the development, outcomes,
      challenges encountered, and lessons learned from MS-PRS and provide our
      recommendations to similar institutions for the development of such a system. 

PMID- 22646744
TI  - Glycosidically bound aroma compounds and impact odorants of four strawberry
      varieties.
AB  - This paper reports the determination of glycosidically bound aroma compounds and
      the olfactometric analysis in four strawberry varieties (Fuentepina, Camarosa,
      Candonga and Sabrina). Different hydrolytic strategies were also studied. The
      results showed significant differences between acid and enzymatic hydrolysis. In
      general terms, the greater the duration of acid hydrolysis, the higher was the
      content of norisoprenoids, volatile phenols, benzenes, lactones, Furaneol, and
      mesifurane. A total of 51 aglycones were identified, 38 of them unreported in
      strawberry. Olfactometric analyses revealed that the odorants with higher
      modified frequencies were Furaneol, gamma-decalactone, ethyl butanoate, ethyl
      hexanoate, ethyl 3-methylbutanoate, diacetyl, hexanoic acid, and (Z)-1,5-octadien
      3-one. This last compound, described as geranium/green/pepper/lettuce (linear
      retention index = 1378), was identified for the first time. Differences with
      regard to fruity, sweet, floral, and green aroma characters were observed among
      varieties. In Candonga and Fuentepina, the green character overpowered the sweet.
      In the other two strawberry varieties sweet attributes were stronger than the
      rest.

PMID- 22646745
TI  - 'But is it a question worth asking?' A reflective case study describing how
      public involvement can lead to researchers' ideas being abandoned.
AB  - BACKGROUND: It is good practice for the public to be involved in developing
      research ideas into grant applications. Some positive accounts of this process
      have been published, but little is known about when their reactions are negative
      and when researchers' ideas are abandoned. OBJECTIVE: To present a case study
      account of when an academic-led idea for funding was not supported by stroke
      survivors and carers who were asked to contribute to its development, together
      with a reflection on the implications of the case from all the stakeholders
      involved. DESIGN: A reflective case study of a research idea, developed by an
      academic researcher, on which stakeholders were consulted. PARTICIPANTS:
      University researchers, clinicians, public involvement managers, and stroke
      survivors and carers from the NIHR's Stroke Research Network. FINDINGS: Although
      the idea met with the approval of health professionals, who were keen to develop
      it into a funding bid, the stroke survivors and carers did not think the idea
      worth pursuing. This lack of patient and carer support led to the idea being
      abandoned. Reflecting on this, those involved in the consultation believed that
      the savings accrued from abandoning the idea, in terms of ensuring that public
      money is not wasted, should be seen as an important benefit of public involvement
      in the research process. CONCLUSION: Little is known about the role of the public
      in the abandonment of research ideas. We recommend that further research is
      undertaken into this important contribution that patients and the public can make
      to health research.

PMID- 22646747
TI  - Neuroblastoma: the impact of biology and cooperation leading to personalized
      treatments.
AB  - Neuroblastoma is the most common extra-cranial solid tumor in children. It is a
      heterogeneous disease, consisting of neural crest-derived tumors with remarkably
      different clinical behaviors. It can present in a wide variety of ways, including
      lesions which have the potential to spontaneously regress, or as an extremely
      aggressive form of metastatic cancer which is resistant to all forms of modern
      therapy. They can arise anywhere along the sympathetic nervous system. The median
      age of presentation is approximately 18 months of age. Urinary catecholamines
      (HVA and VMA) are extremely sensitive and specific tumor markers and are used in
      diagnosis, treatment response assessment and post-treatment surveillance. The
      largest national treatment groups from North America, Europe and Japan have
      formed the International Neuroblastoma Risk Group Task Force (INRG) to identify
      prognostic factors, to understand the mechanisms of tumorigenesis in this rare
      disease and to develop multi-modality therapies to improve outcomes and decrease
      treatment-related toxicities. This international cooperation has resulted in a
      significant leap in our understanding of the molecular pathogenesis of
      neuroblastoma. Lower staged disease can be cured if the lesion is resectable.
      Treatment of unresectable disease (loco-regional and metastatic) is stratified
      depending on clinical features (age at presentation, staging investigations) and
      specific tumor biological markers that include histopathological analyses,
      chromosomal abnormalities and the quantification of expression of an oncogene
      (MYCN). Modern treatment of high-risk neuroblastoma is the paradigm for the
      evolution of therapy in pediatric oncology. Outcomes have improved substantially
      with multi-modality therapy, including chemotherapy, surgery, radiation therapy,
      myeloablative therapy with stem cell transplant, immunotherapy and
      differentiation therapy; these comprise the standard of care worldwide. In
      addition, newer targeted therapies are being tested in phase I/II trials. If
      successful these agents will be incorporated into mainstream treatment programs.

PMID- 22646746
TI  - Transcriptome profiling of the demosponge Amphimedon queenslandica reveals genome
      wide events that accompany major life cycle transitions.
AB  - BACKGROUND: The biphasic life cycle with pelagic larva and benthic adult stages
      is widely observed in the animal kingdom, including the Porifera (sponges), which
      are the earliest branching metazoans. The demosponge, Amphimedon queenslandica,
      undergoes metamorphosis from a free-swimming larva into a sessile adult that
      bears no morphological resemblance to other animals. While the genome of A.
      queenslandica contains an extensive repertoire of genes very similar to that of
      complex bilaterians, it is as yet unclear how this is drawn upon to coordinate
      changing morphological features and ecological demands throughout the sponge life
      cycle. RESULTS: To identify genome-wide events that accompany the pelagobenthic
      transition in A. queenslandica, we compared global gene expression profiles at
      four key developmental stages by sequencing the poly(A) transcriptome using SOLiD
      technology. Large-scale changes in transcription were observed as sponge larvae
      settled on the benthos and began metamorphosis. Although previous systematics
      suggest that the only clear homology between Porifera and other animals is in the
      embryonic and larval stages, we observed extensive use of genes involved in
      metazoan-associated cellular processes throughout the sponge life cycle. Sponge
      specific transcripts are not over-represented in the morphologically distinct
      adult; rather, many genes that encode typical metazoan features, such as cell
      adhesion and immunity, are upregulated. Our analysis further revealed gene
      families with candidate roles in competence, settlement, and metamorphosis in the
      sponge, including transcription factors, G-protein coupled receptors and other
      signaling molecules. CONCLUSIONS: This first genome-wide study of the
      developmental transcriptome in an early branching metazoan highlights major
      transcriptional events that accompany the pelagobenthic transition and point to a
      network of regulatory mechanisms that coordinate changes in morphology with
      shifting environmental demands. Metazoan developmental and structural gene
      orthologs are well-integrated into the expression profiles at every stage of
      sponge development, including the adult. The utilization of genes involved in
      metazoan-associated processes throughout sponge development emphasizes the
      potential of the genome of the last common ancestor of animals to generate
      phenotypic complexity.

PMID- 22646748
TI  - Quantification of multiple infections of Plasmodium falciparum in vitro.
AB  - BACKGROUND: Human malaria infections caused by the parasite Plasmodium falciparum
      often contain more than one genetically distinct parasite. Despite this fact,
      nearly all studies of multiple strain P. falciparum infections have been limited
      to determining relative densities of each parasite within an infection. In light
      of this, new methods are needed that can quantify the absolute number of
      parasites within a single infection. METHODS: A quantitative PCR (qPCR) method
      was developed to track the dynamic interaction of P. falciparum infections
      containing genetically distinct parasite clones in cultured red blood cells.
      Allele-specific primers were used to generate a standard curve and to quantify
      the absolute concentration of parasite DNA within multi-clonal infections.
      Effects on dynamic growth relationships between parasites under drug pressure
      were examined by treating mixed cultures of drug sensitive and drug resistant
      parasites with the anti-malarial drug chloroquine at different dosing schedules.
      RESULTS: An absolute quantification method was developed to monitor the dynamics
      of P. falciparum cultures in vitro. This method allowed for the observation of
      competitive suppression, the reduction of parasites numbers due to the presence
      of another parasite, and competitive release, the improved performance of a
      parasite after the removal of a competitor. These studies demonstrated that the
      presence of two parasites led to the reduction in density of at least one
      parasite. The introduction of drug to a mixed culture containing both a drug
      resistant and drug sensitive parasites resulted in an increased proportion of the
      drug resistant parasite. Moreover, following drug treatment, the resistant
      parasite experienced competitive release by exhibiting a fitness benefit greater
      than simply surviving drug treatment, due to the removal of competitive
      suppression by the sensitive parasite. CONCLUSIONS: The newly developed assay
      allowed for the examination of the dynamics of two distinct clones in vitro; both
      competitive suppression and release were observed. A deeper understanding of the
      dynamic growth responses of multiple strain P. falciparum infections, with and
      without drug pressure, can improve the understanding of the role of parasite
      interactions in the spread of drug resistant parasites, perhaps suggesting
      different treatment strategies.

PMID- 22646749
TI  - Engineering of Aerococcus viridans L-lactate oxidase for site-specific
      PEGylation: characterization and selective bioorthogonal modification of a S218C
      mutant.
AB  - A defined bioconjugate of Aerococcus viridans L-lactate oxidase and poly(ethylene
      glycol) 5000 was prepared and characterized in its structural and functional
      properties in comparison to the unmodified enzyme. Because the L-lactate oxidase
      in the native form does not contain cysteines, we introduced a new site for
      chemical modification via thiol chemistry by substituting the presumably surface
      exposed serine-218, a nonconserved residue in the amino acid sequence, with
      cysteine. The resulting S218C mutant was isolated from Escherichia coli and shown
      in kinetic assays to be similarly (i.e., about half as) active as the native
      enzyme, thus validating the structure-guided design of the mutation. Using
      maleimide-activated methoxypoly(ethylene glycol) 5000 in about 10-fold molar
      excess over protein, the S218C mutant was converted in high yield (94%) into
      PEGylated derivative, while the native enzyme was totally unreactive under
      equivalent conditions. PEGylation caused only a relatively small decrease (30%)
      in the specific activity of the S218C mutant, and it did not change the protein
      stability. PEGylation went along with enhancement of the apparent size of the
      homotetrameric L-lactate oxidase in gel permeation chromatography, from 170 kDa
      to 250 kDa. The protein hydrodynamic diameter determined by dynamic light
      scattering increased from 11.9 nm in unmodified S218C mutant to 16.4 nm in the
      PEGylated form. Site-selective PEGylation of the mutated L-lactate oxidase, using
      orthogonal maleimide-thiol coupling, could therefore facilitate incorporation of
      the enzyme into biosensors currently employed for determination of blood L
      lactate levels, and it could also support different applications of the enzyme in
      applied biocatalysis.

PMID- 22646750
TI  - Screening for cognitive impairment: comparing the performance of four instruments
      in primary care.
AB  - OBJECTIVES: To determine whether brief cognitive screening tests perform as well
      as a longer screening test in diagnosis of cognitive impairment, no dementia
      (CIND) or dementia. DESIGN: A cross-sectional comparison of cognitive screening
      tests to an independent criterion standard evaluation using Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
      Performance of the cognitive screening tests for identifying dementia, and
      separately for identifying dementia or CIND, was characterized using sensitivity,
      specificity, likelihood ratios, and diagnostic odds ratios. SETTING: Three
      Department of Veterans Affairs primary care clinics. PARTICIPANTS: Of 826
      independently living veterans aged 65 and older without a prior diagnosis of
      dementia, 639 participated and 630 were assigned a research diagnosis.
      MEASUREMENTS: Screening tests included the modified Mini-Mental State Examination
      (3MS; average time to administer, 17 minutes) and three brief instruments: the
      Memory Impairment Screen (MIS; 4 minutes), the Mini-Cog (3 minutes), and a novel
      two-item functional memory screen (MF-2; 1.5 minutes). RESULTS: Participants were
      aged 74.8 on average and were mostly white or black. They were mostly male
      (92.9%) and had been prescribed a mean of 7.7 medications for chronic conditions.
      The prevalence of dementia and CIND was 3.3% and 39.2%, respectively. Sensitivity
      and specificity for dementia were 86% and 79% for the 3MS, 76% and 73% for the
      Mini-Cog, 43% and 93% for the MIS, and 38% and 87% for the MF-2, respectively.
      CONCLUSION: In individuals without a prior diagnosis of cognitive impairment, the
      prevalence of dementia was low, but the prevalence of CIND was high. The 3MS and
      Mini-Cog had reasonable performance characteristics for detecting dementia, but a
      definitive diagnosis requires additional evaluation.

PMID- 22646751
TI  - Ruthenium-catalyzed highly regioselective cyclization of ketoximes with alkynes
      by C-H bond activation: a practical route to synthesize substituted
      isoquinolines.
AB  - Aromatic and heteroaromatic ketoximes underwent cyclization with alkynes in the
      presence of a catalytic amount of [{RuCl(2)(p-cymene)}(2)] and NaOAc to give
      isoquinoline derivatives in good to excellent yields in a highly regioselective
      manner.

PMID- 22646752
TI  - Improved local control of rectal cancer reduces distant metastases.
AB  - AIM: The purpose of the present national study was to determine whether improved
      local control has been accompanied by a change in the incidence of metastases.
      METHOD: The data were from a national population-based rectal cancer registry and
      included all 6501 rectal cancer patients treated for cure. The study periods were
      1993-1997, 1998-2000, 2001-2003 and 2004-2006. RESULTS: Major changes in the
      handling of rectal cancer from the first to the last study period included an
      increased use of MRI from zero to 81% and the use of preoperative radiotherapy
      from 5% to 20%. The proportion of patients with circumferential resection margin
      (CRM) <=2mm decreased from 23% to 13%. The 4-year rate of local recurrence
      decreased from 13% to 8% (P<0.001), the overall survival increased from 65% to
      73% (P<0.001) and the incidence of distant metastases decreased from 25% to 19%
      (P<0.001) from the first to the last period. The risk of metastases decreased by
      29% (hazard ratio 0.71, 95% CI 0.60-0.84). CONCLUSION: Improved diagnostics and
      treatment of rectal cancer aiming at better local control and survival have
      resulted in a significant reduction in the incidence of distant metastases.

PMID- 22646753
TI  - The fate of ZnO nanoparticles administered to human bronchial epithelial cells.
AB  - A particular challenge for nanotoxicology is the evaluation of the biological
      fate and toxicity of nanomaterials that dissolve in aqueous fluids. Zinc oxide
      nanomaterials are of particular concern because dissolution leads to release of
      the toxic divalent zinc ion. Although zinc ions have been implicated in ZnO
      cytotoxicity, direct identification of the chemical form of zinc taken up by
      cells exposed to ZnO nanoparticles, and its intracellular fate, has not yet been
      achieved. We combined high resolution X-ray spectromicroscopy and high elemental
      sensitivity X-ray microprobe analyses to determine the fate of ZnO and less
      soluble iron-doped ZnO nanoparticles following exposure to cultures of human
      bronchial epithelial cells, BEAS-2B. We complemented two-dimensional X-ray
      imaging methods with atomic force microscopy of cell surfaces to distinguish
      between nanoparticles that were transported inside the cells from those that
      adhered to the cell exterior. The data suggest cellular uptake of ZnO
      nanoparticles is a mechanism of zinc accumulation in cells. Following uptake, ZnO
      nanoparticles dissolved completely generating intracellular Zn(2+) complexed by
      molecular ligands. These results corroborate a model for ZnO nanoparticle
      toxicity that is based on nanoparticle uptake followed by intracellular
      dissolution.

PMID- 22646754
TI  - Improving quality of delirium care in a general medical service with established
      interdisciplinary care: a controlled trial.
AB  - BACKGROUND: Clinical practice guidelines have been developed to improve
      screening, prevention and management of delirium. AIMS: To implement delirium
      guidelines in general medical patients to reduce incidence and duration of
      delirium and improve outcomes in delirious patients. METHODS: Implementation was
      led by a multidisciplinary team of clinicians and project staff on one medical
      ward. Evaluation was undertaken as a controlled trial in patients aged 65 years
      or older with/at risk of delirium, compared with a control medical ward.
      Interventions included risk screening, delirium detection, multidisciplinary
      education, ward modifications including a four-bed delirium bay, behaviour and
      medication protocols, and use of nursing assistant and volunteers. Primary
      outcome measures were incidence and duration of delirium; secondary outcomes were
      length of stay, mortality, falls and discharge destination in delirious subgroup.
      Process measures included ward moves, use of neuroleptics, allied health review
      and delirium bay use. RESULTS: Of 206 consenting older medical patients, 22% were
      delirious at admission and 44% were at risk. No incident cases of delirium were
      identified. In the delirious subgroup, significantly fewer intervention
      participants were discharged with persistent delirium (32% vs 71%, P = 0.016),
      with trends to reduced inpatient mortality (0% vs 18.5%, P = 0.07) and falls (11%
      vs 22%, P = 0.16), at the expense of a longer medical ward stay (16 days vs 8
      days, P = 0.01). CONCLUSIONS: Low incidence of new delirium may reflect the
      established interdisciplinary care environment. Improved outcomes in the
      delirious group are encouraging although implementation was costly, including
      increased length of acute ward stay.

PMID- 22646755
TI  - The effect of fractional carbon dioxide lasers on idiopathic guttate
      hypomelanosis: a preliminary study.
AB  - BACKGROUND: Idiopathic guttate hypomelanosis (IGH) is a commonly acquired
      leucoderma that is characterized by discrete, round or oval porcelain-white
      macules ~2-5 mm in diameter that increases in number with age. A variety of
      therapies with variable success rates, including cryotherapy, superficial
      abrasion and topical retinoids are currently being used. OBJECTIVES: The effects
      of fractional CO(2) laser therapy on IGH were investigated in this pilot study.
      PATIENTS AND METHODS: A total of 40 patients with IGH were enrolled. The
      hypopigmented lesions were treated using a 10 600-nm carbon dioxide fractional
      laser (CO(2) FL). Two months after a single treatment, physicians' clinical
      assessments were performed and the patients' overall satisfaction was evaluated.
      RESULTS: The mean age of enrolled patients was 57.5 +/- 10.9 years and the gender
      ratio was 7 : 33. The face was the most commonly treated area, although the
      extremities are epidemiologically the most frequently affected areas. Two months
      after treatment, objective assessments performed by two independent
      dermatologists indicated more than 50% improvement in 36 patients (90%), compared
      with baseline. In addition, 33 patients (82.5%) were very satisfied or satisfied
      with just one session of CO(2) FL treatment. Although a few patients complained
      of long-standing erythema and postinflammatory hyperpigmentation, these problems
      spontaneously resolved within 2 months after the assessments. No other noticeable
      side effects were observed. CONCLUSION: CO(2) FL might be a very convenient and
      effective modality for treating IGH without significant side effects.

PMID- 22646756
TI  - Intra-seasonal dynamics in metabolic processes of 13C/12C and 18O/16O in
      components of Scots pine twigs from southern Siberia interpreted with a
      conceptual framework based on the Carbon Metabolism Oscillatory Model.
AB  - BACKGROUND: Carbon isotope data from conifer trees play an important role in
      research on the boreal forest carbon reservoir in the global carbon cycle. Carbon
      isotopes are routinely used to study interactions between the environment and
      tree growth. Moreover, carbon isotopes became an essential tool for the
      evaluation of carbon assimilation and transport from needles into reserve pools,
      as well as the allocation of stored assimilates within a tree. The successful
      application and interpretation of carbon isotopes rely on the coherence of
      isotopic fractionation modeling. This study employs a new Carbon Metabolism
      Oscillatory Model (CMOM) to interpret the experimental data sets on metabolic
      seasonal dynamics of 13C/12 C and 18O/16O ratios measured in twig components of
      Scots pine growing in southern Siberia (Russia). RESULTS: The dynamics of carbon
      isotopic variables were studied in components of Pinus sylvestris L. in light and
      in dark chambers during the vegetation period from 14 June to 28 July 2006. At
      the beginning of this period water-soluble organic matter, mostly labile sugars
      (including sucrose as the main component) and newly formed bulk needle material,
      displayed relatively "light" delta13C values (depletion in 13 C). Then, 13 C
      content increased again with noticeable "depletion" events in the middle of the
      growth period. A gradual 13 C accumulation took place in the second half of the
      vegetation period. Similar effects were observed both in the light and in the
      dark with some temporal shifts. Environmental factors did not influence the
      delta13C values. A gradual 12C-depletion effect was noticed in needles of the
      previous year. The delta13C values of sucrose and proteins from needle biomass
      altered independently from each other in the light chamber. A distinct negative
      correlation between delta13C and delta18O values was revealed for all studied
      variables. CONCLUSIONS: The abrupt 13C depletion recorded by all tested trees for
      the period from June to July provides clear evidence of the transition from the
      dominant role of reserve carbohydrate pool (RCP) during the first half of the
      growth season to the preferable current year carbohydrate pool (CCP) consumption
      by new needles during its second half. The investigation of the isotopic
      signatures of Pinus sylvestris L. emphasizes the pivotal role of the intra
      seasonal dynamics in carbon metabolism through the transport of assimilates from
      autotrophic (needles) to heterotrophic (twigs) organs of the studied trees. This
      provides an explanation for changes of carbon isotopic values observed within the
      growth season. The CMOM-based results support the hypothesis of the integration
      of three carbohydrate pools by photosynthesizing cells. The fluctuations of the
      carbon isotope ratios in different carbohydrate pools underlie various
      physiological processes in the tree metabolism. The possible mechanisms and
      pathways of formation of these carbohydrate pools are further discussed. Hence,
      CMOM provides a reasonable explanation for the absence of the impact of
      environmental conditions on the needle isotopic variables, the 12C-depletion
      effects and the use of RCP in needles. The model explains the negative
      connections between delta13C and delta18O values in all studied variables.

PMID- 22646757
TI  - Risk factors in the occurrence of molar-incisor hypomineralization amongst a
      group of Iraqi children.
AB  - BACKGROUND.  Despite the worldwide increasing interest in the prevalence studies
      of molar-incisor hypomineralization (MIH), there is still insufficient evidence
      to verify the aetiological factors of this condition. AIMS.  To investigate risk
      factors involved in the development of MIH in a group of school-aged Iraqi
      children. DESIGN.  Seven- to nine-year-old school children (823 of 1000 eligible,
      response rate of 82.3%) had their first permanent molars and incisors evaluated
      using the European Academy of Paediatric Dentistry evaluation criteria for MIH.
      Mothers completed a medical history questionnaire-based interview performed in
      the schools by a trained examiner. RESULTS.  For children with MIH, 6% reported
      no relevant medical history; the remaining 94% reported various medical
      conditions putatively associated with MIH compared with 70% for the non-affected
      group. Post-natal medical conditions (33.3%) were most frequently reported. When
      data were split into the possible risk effect groups, maternal psychological
      stress (OR, 3.24), frequent exposure to ultrasonic scans during the last
      gestational trimester (OR, 2.51) and birth order as a fourth sibling or later
      (OR, 3.17 and 5.73, respectively) were previously unreported significant risk
      factors and postulated as contributing to, or causing the defect. CONCLUSIONS. 
      Children with MIH had experienced a greater number of medical conditions than
      their unaffected peers with no single health event identified as a risk factor.

PMID- 22646758
TI  - Comparison of two IGRT correction strategies in postoperative head-and-neck IMRT
      patients.

PMID- 22646759
TI  - Inactivation of thioredoxin f1 leads to decreased light activation of ADP-glucose
      pyrophosphorylase and altered diurnal starch turnover in leaves of Arabidopsis
      plants.
AB  - Chloroplast thioredoxin f (Trx f) is an important regulator of primary metabolic
      enzymes. However, genetic evidence for its physiological importance is largely
      lacking. To test the functional significance of Trx f in vivo, Arabidopsis
      mutants with insertions in the trx f1 gene were studied, showing a drastic
      decrease in Trx f leaf content. Knockout of Trx f1 led to strong attenuation in
      reductive light activation of ADP-glucose pyrophosphorylase (AGPase), the key
      enzyme of starch synthesis, in leaves during the day and in isolated
      chloroplasts, while sucrose-dependent redox activation of AGPase in darkened
      leaves was not affected. The decrease in light-activation of AGPase in leaves was
      accompanied by a decrease in starch accumulation, an increase in sucrose levels
      and a decrease in starch-to-sucrose ratio. Analysis of metabolite levels at the
      end of day shows that inhibition of starch synthesis was unlikely due to shortage
      of substrates or changes in allosteric effectors. Metabolite profiling by gas
      chromatography-mass spectrometry pinpoints only a small number of metabolites
      affected, including sugars, organic acids and ethanolamine. Interestingly,
      metabolite data indicate carbon shortage in trx f1 mutant leaves at the end of
      night. Overall, results provide in planta evidence for the role played by Trx f
      in the light activation of AGPase and photosynthetic carbon partitioning in
      plants.

PMID- 22646760
TI  - Animal biowarfare research: historical perspective and potential future attacks.
AB  - A biological attack on livestock or poultry could result in the loss of valuable
      animals, costs related to the containment of outbreaks and the disposal of
      carcasses, lost trade and other economic effects involving suppliers,
      transporters, distributors and restaurants; however, it is not possible to secure
      all livestock, and livestock are much less well guarded than human targets. Thus,
      the vulnerability of the livestock industry to the introduction of biological
      agents varies for the following reasons: (i) the majority of lethal and
      contagious biological agents are environmentally resilient, endemic in foreign
      countries and harmless to humans, making it easier for terrorists to acquire,
      handle and deploy these pathogens, (ii) with animals concentrated in fewer
      production facilities and frequently transported between these facilities, a
      single pathogen introduction could cause widespread infection and (iii) the
      extent of human travel around the globe makes it difficult to exclude exotic
      animal diseases as possible biological agents. Historically, many governments
      have developed and planned to use biological agents for direct attacks on
      livestock or poultry. In the past, developed nations have actively developed
      biological weapons to target animals. The potential spectrum of bioterrorism
      ranges from isolated acts against individuals by individuals to tactical and
      strategic military attacks and state-sponsored international terrorism intended
      to cause mass casualties in animals, humans or both. This review provides an
      overview of the past development and use of biological weapons and describes
      potential future attacks.

PMID- 22646761
TI  - Generation of a new bioluminescent model for visualisation of mammary tumour
      development in transgenic mice.
AB  - BACKGROUND: Numerous transgenic models have been generated to study breast
      cancer. However, despite many advantages, traditional transgenic models for
      breast cancer are also burdened with difficulties in early detection and
      longitudinal observation of transgene-induced tumours, which in most cases are
      randomly located and occur at various time points. Methods such as palpation
      followed by mechanical measurement of the tumours are of limited value in
      transgenic models. There is a crucial need for making these previously generated
      models suitable for modern methods of tumour visualisation and monitoring, e.g.
      by bioluminescence-based techniques. This approach was successfully used in the
      current study. RESULTS: A new mouse strain (MMTV-Luc2 mice) expressing Luc2
      luciferase primarily in mammary tissue in females, with low-level background
      expression in internal organs, was generated and bred to homozygosity. After
      these mice were intercrossed with MMTV-PyVT mice, all double transgenic females
      developed mammary tumours by the age of 10 weeks, the localisation and
      progression of which could be effectively monitored using the luminescence-based
      in vivo imaging. Luminescence-based readout allowed for early visualisation of
      the locally overgrown mammary tissue and for longitudinal evaluation of local
      progression of the tumours. When sampled ex vivo at the age of 10 weeks, all
      tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent
      signal. CONCLUSIONS: We have created a novel transgenic strain for visualisation
      and longitudinal monitoring of mammary tumour development in transgenic mice as
      an addition and/or a new and more advanced alternative to manual methods.
      Generation of this mouse strain is vital for making many of the existing mammary
      tumour transgenic models applicable for in vivo imaging techniques.

PMID- 22646762
TI  - Bidirectional crosstalk between platelets and monocytes initiated by Toll-like
      receptor: an important step in the early defense against fungal infections?
AB  - Monocytes are important in the defense against fungal infections due to their
      phagocytic and immunoregulatory functions. Platelets also contribute in such
      immune responses through their release of soluble mediators, including chemokines
      as well as several other soluble mediators. Both monocytes and platelets express
      several Toll-like receptors (TLRs) that can recognize fungal molecules and thus
      initiate intracellular signaling events. TLR ligation on monocytes and platelets
      may thereby be an early immunological event and function as an initiator of a
      local proinflammatory crosstalk between platelets and monocytes resulting in (i)
      monocyte-induced increase of platelet activation and (ii) platelet-associated
      enhancement of the monocyte activation/function. These effects may have clinical
      implications both for the efficiency of antifungal treatment and for the
      predisposition to fungal infections, for example, increased predisposition in
      patients with thrombocytopenia/monocytopenia due to chemotherapy- or disease
      induced bone marrow failure.

PMID- 22646763
TI  - Regulators of the hypoxic response: a growing family.

PMID- 22646765
TI  - BRIM-1, -2 and -3 trials: improved survival with vemurafenib in metastatic
      melanoma patients with a BRAF(V600E) mutation.
AB  - Following Phase I and II studies revealing vemurafenib to be a safe potent
      inhibitor of mutated BRAF in patients with metastatic melanoma, a multicenter
      randomized Phase III trial was carried out to compare vemurafenib with
      dacarbazine in treatment-naive patients. The interim analysis results from this
      trial, BRIM-3, were sufficient for an independent data and safety monitoring
      board to recommend crossover from dacarbazine to vemurafenib, vemurafenib being
      associated with a relative risk reduction of 63% in the risk of death and 74% in
      the risk of death or disease progression compared with dacarbazine (p < 0.001 for
      both comparisons) with an acceptable toxicity profile. Such striking results have
      prompted analysis of our approach to the classification and treatment of
      metastatic melanoma in an age of molecular markers and targeted therapy.

PMID- 22646766
TI  - Vemurafenib (RG67204, PLX4032): a potent, selective BRAF kinase inhibitor.
AB  - Vemurafenib is a potent inhibitor of the mutated BRAF kinase. Phase I and II
      clinical trials of vemurafenib showed response rates of more than 50% in patients
      with metastatic melanoma and BRAF mutation. A Phase III study comparing
      vemurafenib with dacarbazine in 675 previously untreated patients revealed
      overall survival to be 84% (95% CI: 78-89) in the vemurafenib group and 64% (95%
      CI: 56-73) in the dacarbazine group. Vemurafenib was associated with a relative
      reduction of 63% in the risk of death and 74% in the risk of either death or
      disease progression, as compared with dacarbazine (p < 0.001). Progression-free
      survival was longer in those treated with vemurafenib (median: 5.3 vs 1.6 months;
      hazard ratio: 0.26; 95% CI: 0.20-0.33). Response rates were 48% for vemurafenib
      and 5% for dacarbazine. After review of the interim analysis by an independent
      data and safety monitoring board, crossover from dacarbazine to vemurafenib was
      recommended.

PMID- 22646767
TI  - Retinoblastoma tumorigenesis: genetic and epigenetic changes walk hand in hand.
AB  - The rate-limiting step in retinoblastoma tumorigenesis is inactivation of both
      RB1 alleles, but it has remained unclear how this tumor acquires the additional
      changes that constitute a malignant phenotype. Zhang et al. characterized the
      genetic and epigenetic alterations in four retinoblastomas using whole-genome
      analysis techniques. In these samples, the retinoblastoma genome was found to be
      remarkably stable genetically, although recurrent mutations in BCOR were
      identified in 13% of patients. However, an approach that integrated the results
      of ChIP, methylation and expression analysis identified multiple, more frequent
      alterations of the epigenetic landscape. One of the leading genes on the list the
      authors obtained was SYK, a kinase epigenetically upregulated. Knockdown of this
      gene and exposure to small molecules inhibiting the kinase function stopped tumor
      growth in vitro and in vivo, thus offering a new therapeutic target for the
      treatment of retinoblastoma.

PMID- 22646768
TI  - Inhibition of non-small-cell lung cancer growth by combined fulvestrant and
      vandetanib.
AB  - Targeting the EGF receptor (EGFR) with tyrosine kinase inhibitors (TKIs) shows
      clinical efficacy for some non-small-cell lung cancer (NSCLC) patients. Recent
      studies have demonstrated that NSCLCs express estrogen receptors and that
      fulvestrant, an antiestrogen that reduces estrogen receptor protein, inhibits
      cell proliferation. Combination of a TKI targeting EGFR and fulvestrant shows
      greater efficacy than TKI or fulvestrant alone. This study demonstrated that
      treatment of NSCLC cells with vandetanib, a TKI of EGFR and VEGF receptor, and
      fulvestrant showed greater efficacy for inhibition of cell proliferation in vitro
      or xenograft tumor growth in vivo than either drug alone. These preclinical data
      provide rationale for a clinical trial to test efficacy in NSCLC patients.

PMID- 22646769
TI  - The emerging harm of antioxidants in carcinogenesis.
AB  - Early epidemiologic studies have hinted at an anticancer role for multiple
      antioxidant compounds that are present in fresh produce. These substances target
      reactive oxygen and nitrogen species and potentially reduce oxidative damage to
      DNA that results in mutagenic change and potentially the initiation of cancer,
      disease and aging. It is tempting to believe that these compounds, through their
      in vitro actions as observed in cancer cell lines and certain animal experiments,
      may have the same anticarcinogenic role in humans. This article summarizes the
      relationship between fresh produce and antioxidant supplements and cancer risks
      from recent epidemiologic studies as well as identifying worrying trends and
      future directions for research into this most controversial field. Recent
      molecular data suggest that certain antioxidants may contribute towards
      oncogenesis.

PMID- 22646770
TI  - Differences in molecular genetics between pediatric and adult malignant
      astrocytomas: age matters.
AB  - The microscope - the classical tool for the investigation of cells and tissues -
      remains the basis for the classification of tumors throughout the body. Nowhere
      has this been more true than in the grading of astrocytomas. In spite of the fact
      that our parents warned us not to judge a book by its cover, we have continued to
      assume that adult and pediatric malignant gliomas that look the same, will have
      the same mutations, and thus respond to the same therapy. Rapid advances in
      molecular biology have permitted us the opportunity to go inside the cell and
      characterize the genetic events that underlie the true molecular heterogeneity of
      adult and pediatric brain tumors. In this paper, we will discuss some of the
      important clinical differences between pediatric and adult gliomas, with a focus
      on the molecular analysis of these different age groups.

PMID- 22646771
TI  - New oral multitargeted antiangiogenics in non-small-cell lung cancer treatment.
AB  - Non-small-cell lung cancer is a particularly aggressive cancer. Combination
      chemotherapy remains the standard therapy for patients with advanced or
      metastatic disease. However, despite the available treatment options for patients
      who progress beyond first-line therapy, prognosis remains poor. Angiogenesis is a
      tightly regulated process controlled by a delicate balance between pro- and
      antiangiogenic factors and their receptors; tumors induce angiogenesis by
      disrupting this balance and secreting various growth factors. Inhibition of tumor
      related angiogenesis has become an attractive target for anticancer therapy.
      Antiangiogenic strategy includes monoclonal antibodies against VEGF and VEGF
      receptor and small molecule inhibitors of VEGF tyrosine kinase activity (tyrosine
      kinase inhibitors). Tyrosine kinase inhibitors are orally active, small molecules
      that represent a new class of drugs with a relatively high safety profile. They
      are targeted therapies that play their anticancer role interfering with specific
      cell signaling. This review focuses on such oral antiangiogenic agents that have
      been approved and are in advanced clinical development for the treatment of
      patients with advanced non-small-cell lung cancer.

PMID- 22646772
TI  - BCR-ABL1-negative chronic myeloid neoplasms: an update on management techniques.
AB  - Recent discoveries concerning mutations associated with chronic
      myeloproliferative neoplasms have modified our understanding of the biology of
      these incurable diseases and guided us to the development of inhibitors active on
      the constitutively activated JAK-STAT pathway. Concurrently, numerous studies
      dealt with clinical issues; it led to a revised WHO classification; clarified the
      role of mutated JAK2 and leukocytosis in the pathogenesis of cardiovascular
      events; allowed the development of risk prognostic scores and tools for
      monitoring response to therapy; and resulted in completion of Phase III trials
      with JAK2 inhibitor in myelofibrosis. All these results hold the promise of
      improving patient prognostication and therapeutic approach, with the aim of
      efficiently preventing disease-associated complications and, hopefully, to
      improve the dismal survival associated with myelofibrosis. This review discusses
      how to manage, according to current clinical practice, the steps of diagnosis,
      prognostication and therapeutic choices in myeloproliferative neoplasm patients.

PMID- 22646773
TI  - Cryopreservation of ovarian tissue for fertility preservation in young female
      oncological patients.
AB  - Girls and women suffering from a cancer that requires treatment with gonadotoxic
      drugs may experience cessation of reproductive function as a side effect due to
      obliteration of the ovarian pool of follicles. Techniques are now available for
      fertility preservation, such as cryopreservation of mature oocytes, embryos or
      ovarian cortical tissue. Whereas collection of mature oocytes and embryos
      requires at least a 2-week period, ovarian tissue may on short notice be frozen
      prior to treatment and can be transplanted back into women with ovarian failure.
      Transplanted frozen/thawed tissue supports survival and growth of follicles,
      giving rise to menstrual cycles and hormone production for several years.
      Worldwide, the procedure has resulted in the birth of 15 healthy children. Many
      cancer patients including girls and young women want fertility preservation, and
      the techniques are now being further developed and implemented in several
      centers.

PMID- 22646774
TI  - Appropriate management of cutaneous adverse events maximizes compliance with
      sorafenib treatment: a single-center experience.
AB  - AIMS: This report describes a positive experience of adverse event (AE)
      management of a multidisciplinary clinical team and 18 patients with late-stage
      renal cell carcinoma and hepatocellular carcinoma attending the Day Hospital Unit
      of the 'Centro Catanese di Oncologia Humanitas' (Italy) over a 2-year period.
      METHODS: The management strategy was based on preventive measures for reducing
      the development of cutaneous AEs, including pain, risk of infection and patient
      discomfort, while avoiding the discontinuation or the reduction of the sorafenib
      dosage. RESULTS: As of July 2011, eight patients were still under treatment with
      sorafenib; seven patients experienced cutaneous AEs and two reported severe
      cutaneous AEs. CONCLUSION: Our treatment approach seemed to reduce the incidence
      and/or severity of AEs, keeping patients in treatment, which is essential for
      good treatment outcomes.

PMID- 22646775
TI  - Efficacy and safety of sunitinib in Chinese patients with imatinib-resistant or 
      intolerant gastrointestinal stromal tumors.
AB  - AIMS: To assess the efficacy and safety of sunitinib in Chinese patients with
      imatinib-resistant or -intolerant gastrointestinal stromal tumors (GISTs), and
      evaluate the impact of genotype on sunitinib efficacy. MATERIALS & METHODS: In a
      single-arm retrospective study, 55 patients with recurrent or metastatic GISTs
      who were resistant or intolerant to prior imatinib treatment received sunitinib
      for at least one treatment cycle. RESULTS: The median progression-free survival
      was 35 weeks (95% CI: 24.6-45.4) in patients who received sunitinib 37.5 mg/day
      as a continuous daily dose versus 30 weeks (95% CI: 12.8-47.2) in those who
      received sunitinib 50 mg/day as a 4-weeks-on, 2-weeks-off (4/2) schedule (p =
      0.707). The median overall survival of all patients was 86 weeks (95% CI: 75.0
      97.0). Patients with KIT exon 9 mutations had a significantly longer progression
      free survival compared with those with KIT exon 11 mutations and patients with
      wild-type GISTs (p = 0.022). Sunitinib therapy was well tolerated, with most
      adverse events rated as grade 1 or 2 in severity. The sunitinib 37.5 mg/day
      continuous daily dose schedule was better tolerated by Chinese GIST patients than
      the 50 mg/day 4/2 schedule. CONCLUSION: Sunitinib was effective and well
      tolerated in Chinese patients with imatinib-resistant or -intolerant GISTs.
      Patients with KIT exon 9 mutations showed the best efficacy. A 37.5 mg/day
      continuous daily dose sunitinib dosing schedule appears to be the optimal choice
      for Chinese patients due to a decreased incidence of adverse events.

PMID- 22646776
TI  - Tetanus toxoid reactive lymphadenopathy masquerading as T-cell lymphoma.
AB  - We report a case in which a patient with persistent reactive lymphadenopathy post
      tetanus toxoid vaccination was initially diagnosed as having T-cell
      lymphoma/leukemia. A florid CD4+ T-cell proliferation and pathology
      interpretation, in the absence of complete clinical information, that these cells
      co-expressed CD8 led to the initial diagnosis. Better integration of the clinical
      and pathologic data may have led more rapidly to the final diagnosis.
      Postvaccination responses can mimic lymphoma.

PMID- 22646778
TI  - Adiponectin in breast milk: relation to serum adiponectin concentration in
      lactating mothers and their infants.
AB  - AIMS:   The aims of the study were to determine human breast milk adiponectin
      concentration and to investigate its relationship with serum adiponectin
      concentration in lactating mothers and their infants and also to evaluate the
      relationship between serum adiponectin concentration and anthropometric
      parameters in nurses and infants. METHODS:   We enrolled 60 healthy term
      breastfed (BF) infants and their lactating mothers. Adiponectin was determined by
      radioimmunoassay test in serum and by enzyme-linked immunosorbent assay test in
      human milk (HM). Infants' and mothers' anthropometric parameters were measured.
      RESULTS:   Median (250/00, 750/00) adiponectin concentration in HM was 9.99
      (3.59, 20.52) ng/mL. Serum adiponectin concentration in infants was 60.49 (45.76,
      74.24) MUg/mL and in lactating mothers 21.14 (12.61, 29.66) MUg/mL. Adiponectin
      concentration in HM correlated positively with adiponectin in mothers' serum; r =
      0.60 (p < 0.001) and in infants' serum r = 0.37 (p = 0.015). Adiponectin in HM
      correlated negatively with infants' age r = -0.3 (p = 0.04). Infants' serum
      adiponectin correlated negatively with their weight r = -0.35 (p = 0.005), length
      r = -0.35 (p = 0.006) and age r = -0.46 (p < 0.001) and mothers' serum
      adiponectin with their weight r = -0.37 (p = 0.02) and body mass index r = -0.45
      (p = 0.004). CONCLUSIONS:   The observed correlations between adiponectin in
      mothers, HM and BF infants may be suggestive for a metabolic link between nurses
      and infants through milk.

PMID- 22646780
TI  - Many quantitative trait loci for feather growth in an F(2) broiler * layer cross
      collocate with body weight loci.
AB  - 1. A genome-wide scan of 467 F(2) progeny of a broiler x layer cross was
      conducted to identify quantitative trait loci (QTL) affecting the rate of growth
      of the tail, wing and back feathers, and the width of the breast feather tract,
      at three weeks of age.   2. Correlations between the traits ranged from 0.36 to
      0.61. Males had longer tail and wing feathers and shorter back feathers than
      females. Breast feather tract width was greater in females than males.   3. QTL
      effects were generally additive and accounted for 11 to 45% of sex average
      feather lengths of the breeds, and 100% of the breast feather tract width.
      Positive and negative alleles were inherited from both lines, whereas the layer
      allele was larger than the broiler allele after adjusting for body weight.   4. A
      total of 4 genome-significant and 4 suggestive QTL were detected. At three or 6
      weeks of age, 5 of the QTL were located in similar regions as QTL for body
      weight.   5. Analysis of a model with body weight at three weeks as a covariate
      identified 5 genome significant and 6 suggestive QTL, of which only two were
      coincident with body weight QTL. One QTL for feather length at 148 cM on GGA1 was
      identified at a similar location in the unadjusted analysis.   6. The results
      suggest that the rate of feather growth is largely controlled by body weight QTL,
      and that QTL specific for feather growth also exist.

PMID- 22646779
TI  - Effects of a high oil and fibre diet and supplementary roughage on performance,
      injurious pecking and foraging activities in two layer hybrids.
AB  - 1. The study investigated the feeding of a high oil and fibre diet containing 260
      g/kg organically produced cold pressed sunflower cake or supplemental roughage to
      aviary-housed Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB) layers
      between 20 and 74 weeks of age with outdoor access during summer. 2. Feeding
      roughage was associated with reduced vent injuries, a tendency to improve plumage
      condition, and was accompanied by improved FCR compared with controls. Feeding
      the high oil and fibre diet tended to improve FCR compared with the control diet.
      3. The dry matter of faeces was reduced in both treatments compared with
      controls. Foot pad cleanliness and the proportion of dirty eggs were negatively
      affected by the high oil and fibre diet. Foot health was superior in LB compared
      to LSL. 4. LB used the outdoor hen-runs more than LSL, but LSL consumed more
      litter indoors. Fewer LB hens fed on the control feed were recorded in the
      outdoor hen-runs. Supplemental roughage tended to decrease litter consumption. 5.
      In conclusion, supplemental roughage reduced vent injuries and was correlated
      with foraging activities. Feeding 260 g/kg sunflower cake negatively affected
      hygiene in aviary hens. Sunflower cake is nevertheless a promising alternative
      feedstuff to fulfil the protein requirement in organic layers.

PMID- 22646781
TI  - Head-cloaca controlled current stunning: assessment of brain and heart activity
      and meat quality.
AB  - 1. Behavioural and neural responses of 65 broilers to head-to-cloaca electrical
      stunning were evaluated and meat quality was assessed on two groups of 25
      broilers stunned either head to cloaca, or in a conventional water bath method.
      2. On the EEG recordings, a general epileptiform insult was observed when
      applying a current of 100 mA (100 Hz) or 70 mA (70 Hz) for 1.5 s. This general
      epileptiform insult shows a tonic, clonic and exhaustion phase followed by spikes
      of alpha, beta, theta and delta waves with duration of on average 34 +/- 12 s and
      39 +/- 23 s respectively. These birds may have been unconscious for 20 s or
      longer, according to the correlation dimension analyses. 3. The heart rate
      decreased significantly (P < 0.05) after stunning and recovered after 60 s. 4.
      Within a confidence limit of 95%, taking into account the number of animals with
      a reliable EEG, the chance of an effective stun of all broilers lies between 0.9
      and 1.0 with a current of 70 mA (100 Hz for 1.5 s; n = 28) and with 100 mA (100
      Hz for 1.5 s; n = 27). 5. The shear force of breast fillets was slightly lower (P
      < 0.01) 4 d post mortem compared with the conventional water bath stunned group
      (set at 100 mA, 100 Hz for 10 s). The percentage of fillets and legs without
      blood splashes was higher, and the percentage with severe blood splashes lower-to
      none, for carcases stunned head-cloaca. 6. It can be concluded that broilers are
      effectively stunned with the head-cloaca method by using a controlled current of
      70 mA or 100 mA for 1.5 s. The fillets and legs of bird stunned head-cloaca
      showed fewer blood splashes in the muscles compared with birds stunned in a
      conventional water bath.

PMID- 22646782
TI  - Interaction of transport distance and body weight on preslaughter stress and
      breast meat quality of broilers.
AB  - 1. The objective of the study was to investigate the effect of transport distance
      on blood metabolites and breast meat quality of broilers slaughtered at different
      weights.   2. The study was conducted on Ross 308 broilers from 27 different
      flocks reared under similar conditions. Slaughter weight was classified as <2.0
      kg, 2.0-2.4 kg, and >2.4 kg. Transport distance was categorised as short (65 km),
      medium (115 km) and long (165 km) distance representing 90, 155 and 220 minutes
      at an average 45 km/h speed, for each slaughter weight.   3. Higher heterophils
      and heterophil:lymphocyte (H/L) ratios were obtained for broilers transported
      over a long distance. Long distance transport increased blood albumin, glucose,
      and triglycerides levels for <2.0 kg broilers, which did not differ from broilers
      slaughtered at >2.4 kg after long-distance transport.   4. Broilers slaughtered
      at >2.4 kg after long-distance transport had lower pH(u), and paler and tougher
      breast meat, than those broilers slaughtered at <2.0 kg after long-distance
      transport.   5. A negative correlation was obtained between pH(u) and L*, thawing
      loss and texture. The L* value was negatively correlated with a*; and positively
      correlated with b*, thawing and cooking losses.   6. It was concluded that the
      effect of transport distance could not be evaluated independently of slaughter
      weight. The interaction between transport distance and slaughter weight
      contributes to preslaughter stress and meat quality.

PMID- 22646783
TI  - In vitro screening of lactobacilli isolated from chicken excreta to control
      Salmonella Enteritidis and Typhimurium.
AB  - 1. The aim of this work was to select lactic acid bacteria (LAB) strains from
      chicks and hens of egg-laying strains for potential use to control Salmonellae.  
      2. Nineteen LAB strains obtained from culture collections, and 24 strains
      isolated from excreta of laying hens and chicks, were evaluated for inhibitory
      capacities against two Salmonella serotypes using a "Spot-the-lawn" technique and
      other in vitro properties that could be predictive of antimicrobial activity.  
      3. The size of the inhibition zone differed slightly between Salmonella
      serotypes, however, the mean size of the Salmonella inhibition zone differed
      greatly among the LAB strains. Lactobacillus salivarius, L. plantarum, L.
      rhamnosus and L. reuteri exhibited powerful inhibitory effects to each Salmonella
      strain.   4. The result of the acid tolerance test showed that all L. salivarius,
      L. kitasatonis strains and each of L. ingluviei cannot survive in a low pH
      environment. In the bile acid tolerance assay, growth was inhibited in all
      strains, except L. kitasatonis HE4, and a large inhibition was observed in most
      of the L. salivarius and L. crispatus strains.   5. The results demonstrate that
      some LAB of poultry origin were able to inhibit the growth of Salmonella and
      survive simulated passage through the gastrointestinal tract. The selected LAB
      could act in the lower gastrointestinal tract to prevent salmonellosis in
      poultry.

PMID- 22646784
TI  - Cloning, expression and bioinformatics analysis of the duck TLR 4 gene.
AB  - 1. Toll-like receptors (TLRs) are type I transmembrane proteins that play an
      essential role in the innate immune system. Studies on the structure and function
      of TLRs can be applied to the development of new approaches to control diseases
      of humans and animals.   2. A 3432-bp cDNA encoding duck toll-like receptor 4
      (duTLR4) was cloned from duck splenic lymphocytes using RT-PCR and rapid
      amplification of cDNA ends.   3. The encoded protein, which was predicted to
      contain 843 amino acids, had a molecular weight of 96.01 kDa and included an
      archetypal toll/interleukin-1 receptor domain, a transmembrane domain, and a
      distinctive arrangement of extracellular leucine-rich repeat regions similar to
      chicken TLR4, human TLR4, and mouse TLR4. The duTLR4 showed 82.1% amino acid
      sequence identity with previously described chicken TLR4, and 43.2-45.2% sequence
      identity with mammalian homologs.   4. RT-qPCR analysis indicated that the duTLR4
      gene was strongly expressed in the liver, kidney, spleen, intestine, and brain.

PMID- 22646785
TI  - Effects of high fat diets or prednisolone treatment on femoral head separation in
      chickens.
AB  - 1. The effects of high fat diets and prednisolone treatment were studied to
      understand the etiology of femoral head separation (FHS) in fast growing broiler
      chickens. Dietary effects on production parameters such as growth, feed
      conversion ratio (FCR) and blood chemistry were also measured.   2. Three groups
      of chickens, consisting of 30 birds each, in two replicate pens, were fed
      isonitrogenous diets containing 40 (control), 60, or 80 g poultry fat supplements
      per kg feed. The birds were fed a starter diet containing the fat supplements for
      the first three weeks, then switched to a grower diet containing the same
      supplements for the rest of the experimental period. Two groups of birds were
      also raised with the control diets, but were administered either cholesterol or
      prednisolone intramuscularly at 30 and 32 days of age to evaluate their effects
      on FHS incidences.   3. The chickens were euthanised and necropsied at 37 d of
      age. The presence of femoral head weakness was determined by applying mild
      pressure on the pelvic joint to cause the growth plate to become detached from
      its articular cartilage in affected cases.   4. High fat diets did not change FHS
      incidences, but increased 28 d body weights (BW) and FCR. At 37 d of age the BW
      differences were not significant but the FCR (gain: feed ratio) remained higher
      in high fat fed groups. Prednisolone treatment, by contrast, resulted in
      decreased BW, decreased feed efficiency, increased FHS index, and elevated blood
      lipid levels.   5. The results suggest that high dietary fats do not affect FHS
      incidence in broilers. Prednisolone treatment causes hyperlipidaemia and
      increases FHS index, and may therefore provide a suitable experimental model of
      FHS pathogenesis in growing chickens.

PMID- 22646786
TI  - The effects of phytase and root hydroalcoholic extract of Withania somnifera on
      productive performance and bone mineralisation of laying hens in the late phase
      of production.
AB  - 1. A 6-week study was conducted to investigate the effects of phytase and
      hydroalcoholic extract of Withania somnifera root (WS) on productive performance
      and bone mineralisation of laying hens in the late phase of production.   2.
      Diets were arranged factorially (3 * 2 * 2) and consisted of a positive control
      with adequate Ca (4.37%) and nonphytate P (NPP; 0.39%) and a negative control
      diet with Ca (4.06%) and NPP (0.36 %); three concentrations of Withania somnifera
      (0, 65 and 130 mg/kg diet); and two concentrations of microbial phytase (0 and
      300 U/kg diet).   3. A total of 144 72-week-old Hy-Line W36 laying hens were
      randomly assigned to the 12 treatment groups. Each treatment was replicated 4
      times (4 x 3 hens). Egg production and egg weight were recorded daily, while feed
      intake and egg quality traits were recorded every two weeks. Bone quality traits
      were evaluated at the end of experiment.   4. Withania somnifera supplementation
      increased egg production and lowered egg weight only in the second two weeks of
      the experiment. Addition of phytase significantly depressed specific gravity of
      the eggs for the entire experiment period. No dietary treatment effects were
      observed on egg shell thickness and yolk weight.   5. Withania somnifera at 130
      mg/kg did not affect feed intake. The hens fed on the positive control diet had
      higher albumen weight than the negative control diet in the second two-week
      period. Supplementation of the positive control diet with 65 mg/kg Withania
      somnifera in the absence of phytase significantly improved shell weight compared
      with the negative control (5.779 vs. 5.273 g respectively).   6. Supplementing
      Withania somnifera significantly improved Ca and P retention in tibia bone. In
      addition, an increase in tibia bone P was observed with phytase supplementation.
      There were significant interactions between Withania somnifera content and
      phytase for tibia bone Ca and P.   7. The results of this experiment indicated
      that dietary Withania somnifera has beneficial effects on tibia bone Ca and P
      content, and phytase improved tibia bone P retention without adverse effects on
      productive performance.

PMID- 22646787
TI  - Effects of fermented plant product on growth performance, some blood variables,
      carcase characteristics, and intestinal histology in broilers.
AB  - 1. Fermented plant product (FPP) is a natural fermented food which is produced
      from a mixture of fermented fruit and vegetables, and rice bran (1:9).   2. To
      investigate the effects of FPP on growth performance, some blood variables,
      carcase characteristics and intestinal histology were determined in 192 broilers.
      They were divided into 4 groups, with 4 replicates of 12 chicks each; the chicks
      were provided ad libitum access to a diet consisting of 0, 0.5, 2.0 and 4.0%
      dietary FPP.   3. The crude protein and metabolisable energy concentrations of
      these diets were adjusted to 230 g CP/kg and 13.40 MJ ME/kg for the 7 to 21 d old
      chicks, and 200 g CP/kg and 13.40 MJ ME/kg for the 22 to 49 d old chicks,
      respectively.   4. At 49 d of age, feed intake, body weight gain and feed
      efficiency tended to increase with increase in FPP concentrations. Feed intake
      increased in the 4.0% dietary FPP group, BW gain increased in the 2.0% and 4.0%
      dietary FPP groups and feed efficiency increased in all experimental groups.   5.
      There were no differences among diets in the blood variables and carcase
      characteristics, except for total visceral organ weight, increased in all
      experimental groups.   6. Most of the intestinal villus heights, villus areas,
      epithelial cell areas and cell mitosis tended to increase with increase in FPP
      concentrations; duodenal villus height and cell mitosis in the 2.0 and 4.0%
      dietary FPP groups, and jejunal cell mitosis in all experimental groups were
      significantly increased. Compared with flat cells on the villus apical surface in
      the 0% FPP group, all experimental groups had protuberant cells in all intestinal
      parts.   7. In conclusion, hypertrophy of the villi and epithelial cells was
      observed in the present study, indicating improved growth performance, especially
      in the 4.0% dietary FPP group. Furthermore, increased total visceral organ
      weights suggested that FPP has no harmful effects on broilers.

PMID- 22646788
TI  - The thermostable beta-1,3-1,4-glucanase from Clostridium thermocellum improves
      the nutritive value of highly viscous barley-based diets for broilers.
AB  - 1. Microbial beta-1,3-1,4-glucanases improve the nutritive value of barley-based
      diets for poultry by effectively decreasing the degree of polymerisation of the
      anti-nutritive soluble beta-glucans. Glycoside hydrolases (GHs) acting on
      recalcitrant polysaccharides display a modular architecture comprising a
      catalytic domain linked to one or more non-catalytic Carbohydrate-Binding Modules
      (CBMs).   2. GHs and CBMs have been classified in different families based on
      primary structure similarity (see CAZy webpage at  http://www.cazy.org ). The
      role of CBMs is to anchor the appended GHs into their target substrates,
      therefore eliciting the efficient hydrolysis of structural carbohydrates.   3.
      Here we describe the biochemical properties of the family 16 GH from Clostridium
      thermocellum, termed CtGlc16A. CtGlc16A is a thermostable enzyme that
      specifically acts on beta-1,3-1,4-glucans with a remarkable catalytic activity
      (38000 U/mg protein).   4. CtGlc16A, individually or fused to the family 11 beta
      glucan-binding domain of cellulase CtLic26A-Cel5E of C. thermocellum, was used to
      supplement a highly viscous barley-based diet for broilers.   5. The data showed
      that birds fed on diets supplemented with the recombinant enzymes displayed an
      improved performance when compared with birds given diets not supplemented with
      exogenous enzymes. However, inclusion of the non-catalytic CBMs had no influence
      on the capacity of CtGlc16A to reduce the anti-nutritive effects of soluble beta
      1,3-1,4-glucans.   6. The data suggest that at elevated dosage rates, CBMs might
      be unable to potentiate the catalytic activity of appended catalytic domains;
      this effect may only be revealed when feed enzymes are incorporated at low
      levels.

PMID- 22646789
TI  - Effects of diet acidification and xylanase supplementation on performance,
      nutrient digestibility, duodenal histology and gut microflora of broilers fed
      wheat based diet.
AB  - 1. The objective of this experiment was to study the influences of xylanase and
      citric acid on the performance, nutrient digestibility, digesta viscosity,
      duodenal histology, and gut microflora of broilers fed on a wheat based diet.  
      2. The experiment was carried out as a 2 * 3 factorial arrangement with two
      concentrations of xylanase (0 and 200 mg/kg) and three concentrations of citric
      acid (0, 20 and 40 g/kg). A total of 408 one-day-old chickens with similar body
      weight were distributed into 24 pens with 17 birds/pen. Each dietary treatment
      was given to 4 replicate pens from 0 to 24 d of age. To determine the apparent
      nutrient digestibility, chromic oxide (3 g/kg) was added to the diets as an
      indigestible marker.   3. Xylanase significantly increased body weight gain at 24
      d of age by 1.4% and improved gain-to-feed (G:F) by 3.6%. The inclusion of 40
      g/kg citric acid decreased feed intake and body weight gain by 15.4% and 11.8%,
      respectively. The inclusion of 20 g/kg of citric acid decreased feed intake, but
      it did not affect body weight gain of broilers at 24 d of age. The inclusion of
      20 and 40 g/kg citric acid improved G:F by 3.8 and 4.3% respectively. Xylanase
      significantly decreased the viscosity of digesta and improved retention of DM,
      CP, and energy.   4. Xylanase and citric acid did not have any effect on the
      histo-morphology of the duodenum and intestinal microbial population.   5. In
      conclusion, citric acid at 20 g/kg decreased feed intake, did not have a negative
      effect on body weight gain, and improved G:F. Xylanase decreased digesta
      viscosity, increased nutrient retention and consequently improved performance of
      broilers fed on a wheat based diet.

PMID- 22646790
TI  - The effects of kale (Brassica oleracea ssp. acephala), basil (Ocimum basilicum)
      and thyme (Thymus vulgaris) as forage material in organic egg production on egg
      quality.
AB  - 1. In organic egg production, forage material as part of the diet for laying hens
      is mandatory. The purpose of the present study was to examine the effect of
      feeding with forage materials including maize silage, herbs or kale on egg
      production and various egg quality parameters of the shell, yolk colour, egg
      albumen, sensory properties, fatty acid and carotenoid composition of the egg
      yolk.   2. A total of 5 dietary treatments were tested for 5 weeks, consisting of
      a basal organic feed plus 120 g/hen.d of the following forage materials: 1) maize
      silage (control), 2) maize silage incl. 15 g/kg basil, 3) maize silage incl. 30
      g/kg basil, 4) maize silage incl. 15 g/kg thyme, or 5) fresh kale leaves. Each
      was supplied to three replicates of 20 hens. A total of 300 hens was used.   3.
      Feed intake, forage intake and laying rate did not differ with treatment, but egg
      weight and egg mass produced increased significantly with the kale treatment.  
      4. The egg shell strength tended to be higher with the kale treatment, and egg
      yolk colour was significantly more red with the kale treatment and more yellow
      with basil and kale treatments. The albumen DM content and albumen gel strength
      were lowest with the thyme treatment. By sensory evaluation, the kale treatment
      resulted in eggs with less sulphur aroma, higher yolk colour score, and more
      sweet and less watery albumen taste. Furthermore, the eggs of the kale treatment
      had significantly higher lutein and beta-carotene content. Also, violaxanthin, an
      orange xanthophyll, tended to be higher in kale and eggs from hens receiving
      kale.   5. In conclusion, forage material, especially basil and kale, resulted in
      increased egg production and eggs of high and differentiable quality.

PMID- 22646791
TI  - Pharmacokinetics of gatifloxacin in broiler chickens following intravenous and
      oral administration.
AB  - 1. The pharmacokinetics of gatifloxacin were investigated following intravenous
      and oral administration of a single dose at a rate of 10 mg/kg body weight in
      broiler chicks.   2. Drug concentration in plasma was determined using High
      Performance Liquid Chromatography with ultraviolet detection on samples collected
      at frequent intervals after drug administration.   3. Following intravenous
      administration, the drug was rapidly distributed (t(1/2alpha): 0.33 +/- 0.008 h)
      and eliminated (t(1/2beta): 3.62 +/- 0.03 h; Cl(B): 0.48 +/- 0.002 l/h/kg) from
      the body.   4. After oral administration, the drug was rapidly absorbed (C (max):
      1.74 +/- 0.024 ug/mL; T (max): 2 h) and slowly eliminated (t(1/2beta): 3.81 +/-
      0.07 h) from the body. The apparent volume of distribution (V(d(area))), total
      body clearance (Cl(B)) and mean residence time (MRT) were 3.61 +/- 0.04 l/kg,
      0.66 +/- 0.01 l/h/kg and 7.16 +/- 0.08 h, respectively. The oral bioavailability
      of gatifloxacin was 72.96 +/- 1.10 %.   5. Oral administration of gatifloxacin at
      10 mg/kg is likely to be highly efficacious against susceptible bacteria in
      broiler chickens.

PMID- 22646792
TI  - Interaction between ascites susceptibility and CO(2) during the second half of
      incubation of two broiler lines: the effect on post-hatch development and ascites
      mortality.
AB  - 1. The aim of this study was to investigate if genetic predisposition to ascites
      interacts with changed incubation conditions, and how this might affect the post
      hatch performance and ascites susceptibility.   2. An ascites sensitive (A) and
      resistant (E) broiler line were incubated under standard or high CO(2) conditions
      (up to 4%) from embryonic d 10 onwards. After hatch, chicks were exposed to cold
      from the 15th day of the rearing period to increase the incidence of ascites.  
      3. The A line had a higher post-hatch body weight from week three, higher blood
      pCO(2) from d 21, higher haematocrit at d 35 and d 42, and higher plasma
      corticosterone concentration from d 21 onwards, compared with the E line,
      regardless of incubation conditions, supporting the given selection criteria.
      Ascites mortality did not, however, differ between lines.   4. Incubation under
      high CO(2) conditions during the second half of incubation increased the ascites
      mortality, decreased body weight from week 4 onwards, affected venous blood
      pCO(2), decreased blood pO(2) from d 31, increased haematocrit at d 35 and d 42,
      and lowered the thyroxine and triiodothyronine concentrations at most sampling
      days. These effects were observed in both lines. The results suggested a
      metabolic programming of CO(2) incubated chickens which affected ascites
      susceptibility.

PMID- 22646793
TI  - Rhodanese activity in different tissues of the ostrich.
AB  - 1. The purpose of this investigation was to determine the activity, and compare
      the pattern of distribution, of rhodanese (thiosulphate: cyanide
      sulphurtransferase, EC. 2.8.1.1) in different tissues of male and female
      ostriches.   2. Tissue samples from male and female Blue Neck ostriches were
      assayed for rhodanese activity by the determination of thiocyanate formed by the
      action of the enzyme on thiosulphate and KCN.   3. Rhodanese was present in all
      tissues, and the highest activity was observed in the kidney and liver. Other
      tissues which contained significant activities of rhodanese were the duodenum,
      pancreas, heart, caecum and rectum.   4. Unlike other birds, the proventiculus
      does not appear to have an important role in cyanide detoxification in ostrich
      and, like mammals, the kidney and liver perform this function.   5. The results
      suggest that the main organs harbouring high rhodanese activity in the ostrich
      are associated with sites likely to be required in rhodanese mediated cyanide
      detoxification.

PMID- 22646794
TI  - Modified corrections for London forces in solid-state density functional theory
      calculations of structure and lattice dynamics of molecular crystals.
AB  - Dispersion forces are critical for defining the crystal structures and
      vibrational potentials of molecular crystals. It is, therefore, important to
      include corrections for these forces in periodic density functional theory (DFT)
      calculations of lattice vibrational frequencies. In this study, DFT was augmented
      with a correction term for London-type dispersion forces in the simulations of
      the structures and terahertz (THz) vibrational spectra of the dispersion-bound
      solids naphthalene and durene. The parameters of the correction term were
      modified to best reproduce the experimental crystal structures and THz spectra.
      It was found that the accurate reproduction of the lattice dimensions by
      adjusting the magnitude of the applied dispersion forces resulted in the highest
      quality fit of the calculated vibrational modes with the observed THz
      absorptions. The method presented for the modification of the dispersion
      corrections provides a practical approach to accurately simulating the THz
      spectra of molecular crystals, accounting for inherent systematic errors imposed
      by computational and experimental factors.

PMID- 22646796
TI  - Toward an integrative understanding of narrative and emotion processes in Emotion
      focused therapy of depression: implications for theory, research and practice.
AB  - This paper addresses the fundamental contributions of client narrative disclosure
      in psychotherapy and its importance for the elaboration of new emotional meanings
      and self understanding in the context of Emotion-focused therapy (EFT) of
      depression. An overview of the multi-methodological steps undertaken to
      empirically investigate the contributions of client story telling, emotional
      differentiation and meaning-making processes (Narrative Processes Coding System;
      Angus et al., 1999) in EFT treatments of depression is provided, followed by a
      summary of key research findings that informed the development of a narrative
      informed approach to Emotion-focused therapy of depression (Angus & Greenberg,
      2011). Finally, the clinical practice and training implications of adopting a
      research-informed approach to working with narrative and emotion processes in EFT
      are described, and future research directions discussed.

PMID- 22646795
TI  - Reconciling cladistic and genetic analyses in choreotrichid ciliates (Ciliophora,
      Spirotricha, Oligotrichea).
AB  - Fifty-six features of halteriid, oligotrichid, and choreotrichid ciliates are
      cladistically analysed, including an updated hypothesis about the evolution of
      the somatic ciliary patterns. Based on its morphology, Lynnella clusters with
      Parastrombidinopsis, Parastrombidium, and Strombidinopsis, while it is basal to
      the other choreotrichids in the molecular phylogenies. The two clusters of
      Favella species in small subunit rRNA gene trees are supported by morphological
      features, justifying a separation at genus and family level. The genus Favella
      has a smooth lorica surface and a somatic ciliary pattern comprising a left and
      lateral ciliary field as well as two dorsal kineties and a monokinetidal ventral
      kinety abutting on the right ciliary field. The new genus Schmidingerella n.
      gen., established for the second Favella cluster, groups with Metacylis and
      Rhabdonella in the molecular trees. It differs from Favella in (i) a lorica wall
      with reticulate surface ridges and minute openings and (ii) a ventral kinety that
      is distinctly apart from the right ciliary field and composed of a monokinetidal
      anterior and a dikinetidal posterior portion. The genera Codonaria, Codonella,
      and Codonellopsis are affiliated with the family Dictyocystidae, whose diagnosis
      is improved to include the lorica sac.

PMID- 22646798
TI  - Belimumab  for the management of systemic lupus erythematosus.
AB  - INTRODUCTION: In 2011, Belimumab , a fully humanized monoclonal antibody against
      B lymphocyte stimulator, became the first biological agent to be licensed by the
      United States Food and Drug Administration (FDA) and the European Medicines
      Evaluation Agency (EMEA) for the use in auto-antibody positive adult Systemic
      Lupus Erythematosus (SLE). AREAS COVERED: An overview of the clinical trial data,
      review of the medical and scientific literature following a MEDLINE search forms
      the basis of this expert opinion on biological therapy review. The Belimumab
      International SLE Study Phase III randomized placebo-controlled trials, BLISS-52
      and BLISS-76, met the primary endpoint based on the SLE responder index (SRI) at
      week 52. The trials reported that belimumab 10 mg/kg infusions with standard
      therapy significantly reduced SLE disease activity compared with placebo with
      standard therapy. EXPERT OPINION: The clinical efficacy, safety and tolerability
      of belimumab indicates a potential role for this drug in achieving disease
      control, reducing severity of recurrent flares, reducing morbidity and in the
      long-term achieving a positive long-term impact on quality of life. Belimumab is
      now being introduced in clinical practice and over the next 5 years data on its
      use outside the clinical trials will determine its place in SLE management.

PMID- 22646799
TI  - In situ determination of interfacial energies between heterogeneously nucleated
      CaCO3 and quartz substrates: thermodynamics of CO2 mineral trapping.
AB  - The precipitation of carbonate minerals--mineral trapping--is considered one of
      the safest sequestration mechanisms ensuring long-term geologic storage of CO(2).
      However, little is known about the thermodynamic factors controlling the extent
      of heterogeneous nucleation at mineral surfaces exposed to the fluids in porous
      reservoirs. The goal of this study is to determine the thermodynamic factors
      controlling heterogeneous nucleation of carbonate minerals on pristine quartz
      (100) surfaces, which are assumed representative of sandstone reservoirs. To
      probe CaCO(3) nucleation on quartz (100) in solution and with nanoscale
      resolution, an in situ grazing incidence small-angle X-ray scattering technique
      has been utilized. With this method, a value of alpha' = 36 +/- 5 mJ/m(2) for the
      effective interfacial free energy governing heterogeneous nucleation of CaCO(3)
      has been obtained by measuring nucleation rates at different solution
      supersaturations. This value is lower than the interfacial energy governing
      calcite homogeneous nucleation (alpha ~ 120 mJ/m(2)), suggesting that
      heterogeneous nucleation of calcium carbonate is favored on quartz (100) at
      ambient pressure and temperature conditions, with nucleation barriers between
      2.5% and 15% lower than those expected for homogeneous nucleation. These
      observations yield important quantitative parameters readily usable in reactive
      transport models of nucleation at the reservoir scale.

PMID- 22646800
TI  - Multiple anti-inflammatory pathways triggered by resveratrol lead to amelioration
      of staphylococcal enterotoxin B-induced lung injury.
AB  - BACKGROUND AND PURPOSE: Inhalation of the superantigen,staphylococcal enterotoxin
      B (SEB), leads to the activation of the host T and invariant natural killer (iNK)
      T cells, thereby resulting in acute lung inflammation and respiratory failure but
      the underlying mechanism(s) of disease remain elusive, with limited treatment
      options. In this study, we investigated the therapeutic effectiveness of
      resveratrol, a plant polyphenol, during SEB-induced lung inflammation.
      EXPERIMENTAL APPROACH: C57BL/6 mice were exposed to SEB (50 ug.per mouse),
      administered intranasally, and were treated with resveratrol (100 mg.kg(-1))
      before or after SEB exposure. Lung injury was studied by measuring vascular
      permeability, histopathological examination, nature of infiltrating cells,
      inflammatory cytokine induction in the bronchoalveolar fluid (BALF), apoptosis in
      SEB-activated T cells and regulation of SIRT1 and NF-kappaB signalling pathways.
      KEY RESULTS: Pretreatment and post-treatment with resveratrol significantly
      reduced SEB-induced pulmonary vascular permeability, and inflammation.
      Resveratrol significantly reduced lung infiltrating cells and attenuated the
      cytokine storm in SEB-exposed mice, which correlated with increased caspase-8
      dependent apoptosis in SEB-activated T cells. Resveratrol treatment also markedly
      up-regulated Cd11b+ and Gr1+ myeloid-derived suppressor cells (MDSCs) that
      inhibited SEB-mediated T cell activation in vitro. In addition, resveratrol
      treatment was accompanied by up-regulation of SIRT1 and down-regulation of NF
      kappaB in the inflammatory cells of the lungs. CONCLUSIONS AND IMPLICATIONS: The
      current study demonstrates that resveratrol may constitute a novel therapeutic
      modality to prevent and treat SEB-induced lung inflammation inasmuch because it
      acts through several pathways to reduce pulmonary inflammation.

PMID- 22646801
TI  - Genome-wide analysis of acetivibrio cellulolyticus provides a blueprint of an
      elaborate cellulosome system.
AB  - BACKGROUND: Microbial degradation of plant cell walls and its conversion to
      sugars and other byproducts is a key step in the carbon cycle on Earth. In order
      to process heterogeneous plant-derived biomass, specialized anaerobic bacteria
      use an elaborate multi-enzyme cellulosome complex to synergistically deconstruct
      cellulosic substrates. The cellulosome was first discovered in the cellulolytic
      thermophile, Clostridium thermocellum, and much of our knowledge of this
      intriguing type of protein composite is based on the cellulosome of this
      environmentally and biotechnologically important bacterium. The recently
      sequenced genome of the cellulolytic mesophile, Acetivibrio cellulolyticus,
      allows detailed comparison of the cellulosomes of these two select cellulosome
      producing bacteria. RESULTS: Comprehensive analysis of the A. cellulolyticus
      draft genome sequence revealed a very sophisticated cellulosome system. Compared
      to C. thermocellum, the cellulosomal architecture of A. cellulolyticus is much
      more extensive, whereby the genome encodes for twice the number of cohesin- and
      dockerin-containing proteins. The A. cellulolyticus genome has thus evolved an
      inflated number of 143 dockerin-containing genes, coding for multimodular
      proteins with distinctive catalytic and carbohydrate-binding modules that play
      critical roles in biomass degradation. Additionally, 41 putative cohesin modules
      distributed in 16 different scaffoldin proteins were identified in the genome,
      representing a broader diversity and modularity than those of Clostridium
      thermocellum. Although many of the A. cellulolyticus scaffoldins appear in
      unconventional modular combinations, elements of the basic structural scaffoldins
      are maintained in both species. In addition, both species exhibit similarly
      elaborate cell-anchoring and cellulosome-related gene- regulatory elements.
      CONCLUSIONS: This work portrays a particularly intricate, cell-surface
      cellulosome system in A. cellulolyticus and provides a blueprint for examining
      the specific roles of the various cellulosomal components in the degradation of
      complex carbohydrate substrates of the plant cell wall by the bacterium.

PMID- 22646803
TI  - Altered expression of dermokine in skin disorders.
AB  - BACKGROUND: Although dermokine-beta, a glycoprotein expressed in epithelial
      cells, does not have significant homology to other proteins, its carboxyl
      terminal domain shares a high pI value with many cytokines, suggesting similar
      functions. OBJECTIVE: To better understand the biology of dermokine, we here
      determined its localization under pathological conditions and examined factors
      that regulate its expression. METHODS: We generated an anti-human dermokine
      beta/gamma monoclonal antibody cross-reacting with the mouse protein. Using this
      antibody, immunohistological staining and Western blotting of dermokine
      beta/gamma were performed with various tissue samples. RESULTS: Although human
      dermokine-beta/gamma was expressed in almost all granular layers, upper spinous
      layers of the skin were also stained with anti-dermokine-beta/gamma antibody in
      inflammatory skin disorders. Dermokine-beta/gamma was expressed in
      keratoacanthoma and a part of well-differentiated squamous cell carcinoma (SCC).
      However, dermokine-beta/gamma was not detected in poorly differentiated SCC or
      tumours derived from non-keratinocytes. In mice, dermokine-beta/gamma-expressed
      keratinocytes were increased in models of contact hypersensitivity, ultraviolet
      irradiated skin injury and wound healing. Consistent with expanded distribution
      in inflammatory skin diseases, proinflammatory cytokines such as interleukin
      1beta, interleukin-12, and tumour necrosis factor-alpha augmented dermokine
      beta/gamma expression in cultured human keratinocytes. In contrast, growth
      factors including epidermal growth factor, insulin-like growth factor-I,
      keratinocyte growth factor and transforming growth factor-alpha significantly
      reduced dermokine expression. CONCLUSION: These results provide novel insights
      into the physiological and pathological significance of dermokine in the
      epidermis.

PMID- 22646802
TI  - Avoiding piecemeal research on participation in cervical cancer screening: the
      advantages of a social identity framework.
AB  - BACKGROUND: Cervical cancer screening research has predominantly focused on one
      type of participation, namely compliance with medical recommendations, and has
      largely ignored other types of participation. While there is some research that
      has taken a different approach, findings in this research area are not well
      integrated under a theoretical framework. OBJECTIVE: The aim of this study is to
      show how consideration of a broader definition of participation and better
      integration of the theoretical conceptualization of participation in cervical
      cancer screening are both possible and desirable to enable a better understanding
      of women's experiences of cervical cancer screening specifically and to improve
      women's health generally. MAIN CONCLUSION: It is suggested that alternative types
      of participation in cervical cancer screening warrant further investigation and
      that a social identity theoretical approach offers one way of integrating such
      conceptualizations of participation. The paper also argues for more explicit
      consideration of the role of social processes and of the variables, such as
      power, social identity and relational justice, which are involved in
      participation in cervical cancer screening.

PMID- 22646804
TI  - Obesity and pulmonary disease: unanswered questions.
AB  - Obesity is associated with risk of pulmonary disease, and adversely affects lung
      function. The parallel increase in obesity and asthma suggests the two conditions
      are linked; indeed, they can worsen each other. Obesity and inadequate asthma
      control are associated with poor quality of life, and place a high economic
      burden on public health. Although the obesity-lung interaction is a major issue
      for basic research and clinical studies, various questions remain unanswered. Do
      intrauterine and early life factors impact on the development of obesity and lung
      disease? If so, can this be prevented? Asthma is generally more severe in obese
      subjects, but is adiposity a driver of a new asthma phenotype that features
      greater morbidity and mortality, worse control and decreased response to
      medications? Obese individuals have small lung volumes, hence their airway
      calibre is reduced and airway resistance is increased. What puzzles physicians is
      whether peripheral airways undergo remodelling, which would increase
      bronchoconstriction. Obese asthmatics respond suboptimally to anti-inflammatory
      treatment, which raises the question: 'what drug for what patient?' Life
      expectancy is decreased in obesity and in chronic pulmonary disorders, but does
      obesity protect against or trigger chronic obstructive pulmonary disease? The
      time has come to find answers to these questions.

PMID- 22646805
TI  - Fluorescent nanoaggregates of pentacenequinone derivative for selective sensing
      of picric acid in aqueous media.
AB  - Novel pentacenequinone derivative 3 has been synthesized using the Suzuki-Miyaura
      coupling protocol which forms fluorescent nanoaggregates in aqueous media due to
      its aggregation-induced emission enhancement attributes and selectively senses
      picric acid with a detection limit of 500 ppb.

PMID- 22646806
TI  - Pivotal factors interfering in 24-hour blood pressure fluctuation and arterial
      stiffness in a community of Chinese elderly hypertensive patients.
AB  - AIMS AND OBJECTIVES: To explore which sociodemographic and clinical factors could
      interfere in the parameters of ambulatory blood pressure monitoring and determine
      the affecting factors of Ambulatory Arterial Stiffness Index. BACKGROUND:
      Although the clinical relevance of ambulatory blood pressure monitoring and
      Ambulatory Arterial Stiffness Index have been studied, the explanation of their
      role and related interfering factors remains controversial in patients with
      different disease or age, etc. DESIGN: Cross-sectional study. METHODS: The study
      was carried out between October 2008-October 2009. A convenience sample of
      hypertensive patients over 60 years old was recruited in China. Twenty-four hour
      ambulatory blood pressure monitoring was carried out on the non-dominant arm
      using an oscillometric device. RESULTS: (1) All 95 patients completed the study
      and their ages ranged from 60-76 years. (2) There were statistical differences
      for certain parameters of ambulatory blood pressure monitoring between different
      characteristics of patients. Financial status was an important factor interfering
      in patients' BP fluctuation, especially daytime and 24 hours systolic pressure.
      The higher body mass index the patients had, the higher the pressure was. (3)
      Multiple variants logistic analysis of Ambulatory Arterial Stiffness Index showed
      statistical differences only in coefficient variation of 24-hour diastolic
      pressure and daytime systolic blood pressure. CONCLUSIONS: There are more factors
      that interfered with systolic pressure and diastolic pressure during the day than
      night. Patients who have less nocturnal dipping may have a higher night time
      systolic pressure and diastolic pressure. The coefficient of variation of 24
      hours diastolic pressure and daytime systolic pressure contribute more to
      Ambulatory Arterial Stiffness Index which should arouse practitioners' attention.
      RELEVANCE TO CLINICAL PRACTICE: Ambulatory blood pressure monitoring should be
      used as a routine procedure, as well as Ambulatory Arterial Stiffness Index
      calculated for older hypertensive patients. The findings may be used to guide
      community health providers to pay more attention to the factors that may
      influence BP fluctuation and Ambulatory Arterial Stiffness Index according to
      individual's characteristics.

PMID- 22646807
TI  - Clinical model for ethical cardiopulmonary resuscitation decision-making.
AB  - BACKGROUND: Decisions to withhold cardiopulmonary resuscitation (CPR) for future
      cardiac arrest continue to be problematic, with a lack of consistency in how
      doctors approach this decision. AIMS: To develop a clinical model that can be
      used in education to improve consistency in CPR decision-making. METHODS: A
      qualitative study, using semistructured interviews with a total of 33 senior
      doctors, junior doctors and nurses from two Melbourne hospitals explored how
      decisions to withhold CPR are made. Interviews explored: issues arising; how
      doctors learn to make these decisions; how they deal with disagreement and their
      experiences of performing CPR. The transcripts were coded and analysed
      thematically. RESULTS: Three major themes were identified: CPR as a life-and
      death decision; good and bad dying; and trust. The research also defined the two
      elements to a CPR decision: (i) technical and (ii) ethical. CONCLUSIONS: Applying
      ethical principles commonly used in medicine, a model for ethical CPR decision
      making has been developed that identifies four patient groups, each with a
      different discussion aim. This approach simplifies the complexities of the CPR
      decision, providing a structured way to teach CPR decision-making to doctors and
      thereby achieve greater consistency in the decisions made.

PMID- 22646808
TI  - Glomangioleiomyoma of the orbit--a case report.
AB  - Soft-tissue glomus tumours are benign lesions derived from the glomus bodies,
      which are specialized arteriovenous shunts that serve a thermoregulatory function
      and are concentrated in the distal extremities of the dermis. Glomangioleiomyoma
      is rarely found in the orbit, most likely because of the paucity of smooth muscle
      and glomus bodies in this location. We report the case of a woman with
      exophthalmos in whom computerized tomography and magnetic resonance imaging
      showed a large, lobulated mass in the right intraconal space.

PMID- 22646810
TI  - Short-term effects of CO(2)  and O(2)  on citrate metabolism in illuminated
      leaves.
AB  - Although there is now a considerable literature on the inhibition of leaf
      respiration (CO(2)  evolution) by light, little is known about the effect of
      other environmental conditions on day respiratory metabolism. In particular,
      CO(2)  and O(2)  mole fractions are assumed to cause changes in the tricarboxylic
      acid pathway (TCAP) but the amplitude and even the direction of such changes are
      still a matter of debate. Here, we took advantage of isotopic techniques, new
      simple equations and instant freeze sampling to follow respiratory metabolism in
      illuminated cocklebur leaves (Xanthium strumarium L.) under different CO(2) /O(2)
      conditions. Gas exchange coupled to online isotopic analysis showed that CO(2) 
      evolved by leaves in the light came from 'old' carbon skeletons and there was a
      slight decrease in (13) C natural abundance when [CO(2) ] increased. This
      suggested the involvement of enzymatic steps fractionating more strongly against
      (13) C and thus increasingly limiting for the metabolic respiratory flux as
      [CO(2) ] increased. Isotopic labelling with (13) C(2) -2,4-citrate lead to (13) C
      enriched Glu and 2-oxoglutarate (2OG), clearly demonstrating poor metabolism of
      citrate by the TCAP. There was a clear relationship between the ribulose-1,5
      bisphosphate oxygenation-to-carboxylation ratio (v(o) /v(c) ) and the (13) C
      commitment to 2OG, demonstrating that 2OG and Glu synthesis via the TCAP is
      positively influenced by photorespiration.

PMID- 22646809
TI  - Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory
      cytokines are associated with severe malaria in Mozambican children: a case
      control study.
AB  - BACKGROUND: The factors involved in the progression from Plasmodium falciparum
      infection to severe malaria (SM) are still incompletely understood. Altered
      antibody and cellular immunity against P. falciparum might contribute to increase
      the risk of developing SM. METHODS: To identify immune responses associated with
      SM, a sex- and age-matched case-control study was carried out in 134 Mozambican
      children with SM (cerebral malaria, severe anaemia, acidosis and/or respiratory
      distress, prostration, hypoglycaemia, multiple seizures) or uncomplicated malaria
      (UM). IgG and IgM against P. falciparum lysate, merozoite antigens (MSP-119, AMA
      1 and EBA-175), a Duffy binding like (DBL)-alpha rosetting domain and antigens on
      the surface of infected erythrocytes were measured by ELISA or flow cytometry.
      Plasma concentrations of IL-12p70, IL-2, IFN-gamma, IL-4, IL-5, IL-10, IL-8, IL
      6, IL-1beta, TNF, TNF-beta and TGF-beta1 were measured using fluorescent bead
      immunoassays. Data was analysed using McNemar's and Signtest. RESULTS: Compared
      to UM, matched children with SM had reduced levels of IgG against DBLalpha (P <
      0.001), IgM against MSP-119 (P = 0.050) and AMA-1 (P = 0.047), TGF-beta1 (P <
      0.001) and IL-12 (P = 0.039). In addition, levels of IgG against P. falciparum
      lysate and IL-6 concentrations were increased (P = 0.004 and P = 0.047,
      respectively). Anti-DBLalpha IgG was the only antibody response associated to
      reduced parasite densities in a multivariate regression model (P = 0.026).
      CONCLUSIONS: The lower levels of antibodies found in children with SM compared to
      children with UM were not attributable to lower exposure to P. falciparum in the
      SM group. IgM against P. falciparum and specific IgG against a rosetting PfEMP1
      domain may play a role in the control of SM, whereas an imbalanced pro
      inflammatory cytokine response may exacerbate the severity of infection. A high
      overlap in symptoms together with a limited sample size of different SM clinical
      groups reduced the power to identify immunological correlates for particular
      forms of SM.

PMID- 22646811
TI  - Hospitalized cardiovascular events in patients with diabetic macular edema.
AB  - BACKGROUND: Microvascular and macrovascular complications in diabetes stem from
      chronic hyperglycemia and are thought to have overlapping pathophysiology. The
      aim of this study was to investigate the incidence rate of hospitalized
      myocardial infarctions (MI) and cerebrovascular accidents (CVA) in patients with
      diabetic macular edema (DME) compared with diabetic patients without retinal
      diseases. METHODS: This was a retrospective cohort study of a commercially
      insured population in an administrative claims database. DME subjects (n = 3519)
      and diabetes controls without retinal disease (n = 10557) were matched by age and
      gender. Healthcare claims were analyzed for the study period from 1 January 2002
      to 31 December 2005. Incidence and adjusted rate ratios of hospitalized MI and
      CVA events were then calculated. RESULTS: The adjusted rate ratio for MI was 2.50
      (95% CI: 1.83-3.41, p < 0.001) for DME versus diabetes controls. Predictors of MI
      events were heart disease, history of acute MI, and prior use of antiplatelet or
      anticoagulant drugs. The adjusted rate ratio for CVA was 1.98 (95% CI: 1.39-2.83,
      p < 0.001) for DME versus diabetes controls. Predictors of CVA events were
      cardiac arrhythmia, Charlson comorbidity scores, history of CVA, hyperlipidemia,
      and other cerebrovascular diseases. CONCLUSION: Event rates of MI or CVA were
      higher in patients with DME than in diabetes controls. This study is one of few
      with sufficient sample size to accurately estimate the relationship between DME
      and cardiovascular outcomes.

PMID- 22646812
TI  - Balancing of sulfur storage in maize seed.
AB  - BACKGROUND: A balanced composition of amino acids in seed flour is critical
      because of the demand on essential amino acids for nutrition. However, seed
      proteins in cereals like maize, the crop with the highest yield, are low in
      lysine, tryptophan, and methionine. Although supplementation with legumes like
      soybean can compensate lysine deficiency, both crops are also relatively low in
      methionine. Therefore, understanding the mechanism of methionine accumulation in
      the seed could be a basis for breeding cultivars with superior nutritional
      quality. RESULTS: In maize (Zea mays), the 22- and 19-kDa alpha-zeins are the
      most prominent storage proteins, nearly devoid of lysine and methionine. Although
      silencing synthesis of these proteins through RNA interference (RNAi) raises
      lysine levels in the seed, it fails to do so for methionine. Computational
      analysis of annotated gene models suggests that about 57% of all proteins exhibit
      a lysine content of more than 4%, whereas the percentage of proteins with
      methionine above 4% is only around 8%. To compensate for this low representation,
      maize seeds produce specialized storage proteins, the 15-kDa beta-, 18-kDa and 10
      kDa delta-zeins, rich in methionine. However, they are expressed at variant
      levels in different inbred lines. A654, an inbred with null delta-zein alleles,
      methionine levels are significantly lower than when the two intact delta-zein
      alleles are introgressed. Further silencing of beta-zein results in dramatic
      reduction in methionine levels, indicating that beta- and delta-zeins are the
      main sink of methionine in maize seed. Overexpression of the 10-kDa delta-zein
      can increase the methionine level, but protein analysis by SDS-PAGE shows that
      the increased methionine levels occur at least in part at the expense of
      cysteines present in beta- and gamma-zeins. The reverse is true when beta- and
      gamma-zein expression is silenced through RNAi, then 10-kDa delta-zein
      accumulates to higher levels. CONCLUSIONS: Because methionine receives the sulfur
      moiety from cysteine, it appears that when seed protein synthesis of cysteine
      rich proteins is blocked, the synthesis of methionine-rich seed proteins is
      induced, probably at the translational level. The same is true, when methionine
      rich proteins are overexpressed, synthesis of cysteine-rich proteins is reduced,
      probably also at the translational level. Although we only hypothesize a
      translational control of protein synthesis at this time, there are well known
      paradigms of how amino acid concentration can play a role in differential gene
      expression. The latter we think is largely controlled by the flux of reduced
      sulfur during plant growth.

PMID- 22646814
TI  - Introduction to the special section on biopsychosocial moderators of the stress
      response.

PMID- 22646813
TI  - Spontaneous inflammatory pain model from a mouse line with N-ethyl-N-nitrosourea
      mutagenesis.
AB  - BACKGROUND: N-ethyl-N-nitrosourea mutagenesis was used to induce a point mutation
      in C57BL/6 J mice. Pain-related phenotype screening was performed in 915 G3 mice.
      We report the detection of a heritable recessive mutant in meiotic recombinant
      N1F1 mice that caused an abnormal pain sensitivity phenotype with spontaneous
      skin inflammation in the paws and ears. METHODS: We investigated abnormal sensory
      processing, neuronal peptides, and behavioral responses after the induction of
      autoinflammatory disease. Single-nucleotide polymorphism (SNP) markers and
      polymerase chain reaction product sequencing were used to identify the mutation
      site. RESULTS: All affected mice developed paw inflammation at 4-8 weeks.
      Histological examinations revealed hyperplasia of the epidermis in the inflamed
      paws and increased macrophage expression in the spleen and paw tissues.
      Mechanical and thermal nociceptive response thresholds were reduced in the
      affected mice. Locomotor activity was decreased in affected mice with inflamed
      hindpaws, and this reduction was attributable to the avoidance of contact of the
      affected paw with the floor. Motor strength and daily activity in the home cage
      in the affected mice did not show any significant changes. Although Fos
      immunoreactivity was normal in the dorsal horn of affected mice, calcitonin gene
      related peptide immunoreactivity significantly increased in the deep layer of the
      dorsal horn. The number of microglia increased in the spinal cord, hippocampus,
      and cerebral cortex in affected mice, and the proliferation of microglia was
      maintained for a couple of months. Two hundred eighty-five SNP markers were used
      to reveal the affected gene locus, which was found on the distal part of
      chromosome 18. A point mutation was detected at A to G in exon 8 of the pstpip2
      gene, resulting in a conserved tyrosine residue at amino acid 180 replaced by
      cysteine (Y180 C). CONCLUSIONS: The data provide definitive evidence that a
      mutation in pstpip2 causes autoinflammatory disease in an N-ethyl-N-nitrosourea
      mutagenesis mouse model. Thus, our pstpip2 mutant mice provide a new model for
      investigating the potential mechanisms of inflammatory pain.

PMID- 22646815
TI  - On the origin of matrix metalloproteinase-2 and -9 in blood platelets.
AB  - To date, several matrix metalloproteinases (MMPs) have been identified in human
      platelets. In most research studies, the platelets are obtained using the
      isolation method from plasma by centrifugation and washing. The metalloproteinase
      content in the platelets can be affected by the isolation technique and the
      leukocyte contamination. In this work, we studied the influence of the isolation
      method on the detection of platelet MMPs and explore the expression of these
      enzymes in megakaryoblastic MEG-01 cells. We investigated the expression of mRNAs
      encoding for MMP-2 and -9 in platelets and MEG-01 cells. Using gelatin zymography
      and western blotting, we examined the expression and release of MMP-2 and 9 by
      platelets and MEG-01 cells and checked whether the amount of the released MMPs
      depends on the volume of tested platelet and leukocyte contamination. To
      investigate the MMP-2 expression profile, we used zymography and flow cytometry.
      Platelets, in contrast to the MEG-01 cells, neither contain mRNA for MMP-2 nor 
      9. The platelets contain pro-MMP-2 and release it during the activation. The
      population of uncontaminated (leukocytes<0.02%) platelets contained no MMP-9 or
      the active form of MMP-2. We have observed that the activity of MMP-2 in platelet
      lysate is proportional to their mean volume and that the MMP-2 activity may not
      be detected if very small platelets are examined. We conclude that the detection
      of gelatinases in platelets depends on platelet isolation techniques and the
      degree of leukocyte contamination.

PMID- 22646816
TI  - Chronic lymphocytic leukemia in African Americans.
AB  - Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the United
      States with almost 4390 attributable deaths per year. Epidemiologic data compiled
      by the Surveillance, Epidemiology and End Results (SEER) program identifies
      important differences in incidence and survival for African Americans with CLL.
      Although the incidence of CLL is lower among African Americans than among
      Caucasians (4.6 and 6.2 per 100 000 men, respectively), age-adjusted survival is
      inferior. African American patients with CLL are almost twice as likely to die
      from a CLL-related complication in the first 5 years after diagnosis as are
      Caucasian patients with CLL. The biologic basis for these observations is almost
      entirely unexplored, and a comprehensive clinical analysis of African American
      patients with CLL is lacking. This is the subject of the present review.

PMID- 22646817
TI  - Lipophilic extractives from the cortex and pith of elephant grass ( Pennisetum
      purpureum Schumach.) stems.
AB  - The composition of lipophilic extractives in the cortex and pith of elephant
      grass ( Pennisetum purpureum  Schumach.) stems was thoroughly studied by gas
      chromatography-mass spectrometry. The predominant compounds were fatty acids
      followed by sterols (in free and conjugated forms as esters and glycosides).
      Other steroid compounds, as steroid hydrocarbons and ketones, were also present.
      Additionally, important amounts of mono-, di-, and triglycerides were identified.
      Other aliphatic series such as n-alkanes, n-fatty alcohols, and n-alkyl
      ferulates, together with tocopherols and a series of high molecular weight
      esters, were also found, although in minor amounts. The analyses also revealed
      the presence of a beta-diketone (12,14-tritriacontanedione), which was
      particularly abundant in the cortex. Finally, two lignans, matairesinol and
      syringaresinol, were also detected. In general terms, the abundances of the
      different classes of compounds were higher in the pith, except for the series of
      n-fatty alcohols, n-alkyl ferulates, beta-diketones, and lignans, which were more
      prominent in the cortex.

PMID- 22646818
TI  - Provider views about responsibility for medication adherence and content of
      physician-older patient discussions.
AB  - OBJECTIVES: To investigate provider opinions about responsibility for medication
      adherence and examine physician-patient interactions to illustrate how adherence
      discussions are initiated. DESIGN: Focus group discussions with healthcare
      providers and audio taped outpatient office visits with a separate group of
      providers. SETTING: Focus group participants were recruited from multispecialty
      practice groups in New Jersey and Washington, District of Columbia. Outpatient
      office visits were conducted in primary care offices in Northern California.
      PARTICIPANTS: Twenty-two healthcare providers participated in focus group
      discussions. One hundred patients aged 65 and older and 28 primary care
      physicians had their visits audio taped. MEASUREMENTS: Inductive content analysis
      of focus groups and audio taped encounters. RESULTS: Focus group analyses
      indicated that providers feel responsible for assessing medication adherence
      during office visits and for addressing mutable factors underlying nonadherence,
      but they also believed that patients were ultimately responsible for taking
      medications and voiced reluctance about confronting patients about nonadherence.
      The 100 patients participating in audio taped encounters were taking a total of
      410 medications. Of these, 254 (62%) were discussed in a way that might address
      adherence; physicians made simple inquiries about current patient medication use
      for 31.5%, but they made in-depth inquiries about adherence for only 4.3%. Of 39
      identified instances of nonadherence, patients spontaneously disclosed 51%.
      CONCLUSION: The lack of intrusive questions about medication taking during office
      visits may reflect poor provider recognition of the questions needed to assess
      adherence fully. Alternatively, provider beliefs about patient responsibility for
      adherence may hinder detailed queries. A paradigm of joint provider-patient
      responsibility may be needed to better guide discussions about medication
      adherence.

PMID- 22646819
TI  - Tacrolimus without or with the addition of conventional immunosuppressive
      treatment in juvenile autoimmune hepatitis.
AB  - AIM: To investigate tacrolimus (Tac)-based treatment in juvenile autoimmune
      hepatitis (AIH). Twenty patients (13 girls; age, 8-17 years; median, 13.25 years)
      with AIH were treated with two daily oral doses of Tac. Six of them had advanced
      liver disease and/or cirrhosis. METHODS: Drug concentrations in blood were
      measured regularly, and the target trough levels were 2.5-5 ng/mL. The patients
      were followed up for 1 year. Their clinical, biochemical, immunological and
      histological status was obtained at baseline and after 1 year. RESULTS: In three
      cases, Tac alone led to complete remission. In 14 cases, additional low doses of
      prednisolone or azathioprine were used for a short time to achieve remission. In
      two cases, the treatment was discontinued: in one because of therapeutic failure,
      in another because of a suspected but unverified adverse event. Ten patients
      reported headache and/or recurrent abdominal pain. Two patients developed
      inflammatory bowel disease. Renal function remained intact. CONCLUSION: Tac is a
      promising alternative first line of treatment for AIH. Although monotherapy with
      Tac is usually not sufficient to achieve complete remission, the prednisolone and
      azathioprine doses can be drastically reduced, and most of their side effects
      avoided.

PMID- 22646820
TI  - Metallic adhesion layer induced plasmon damping and molecular linker as a
      nondamping alternative.
AB  - Drastic chemical interface plasmon damping is induced by the ultrathin (~2 nm)
      titanium (Ti) adhesion layer; alternatively, molecular adhesion is implemented
      for lithographic fabrication of plasmonic nanostructures without significant
      distortion of the plasmonic characteristics. As determined from the homogeneous
      linewidth of the resonance scattering spectrum of individual gold nanorods, an
      ultrathin Ti layer reduces the plasmon dephasing time significantly, and it
      reduces the plasmon scattering amplitude drastically. The increased damping rate
      and decreased plasmon amplitude are due to the dissipative dielectric function of
      Ti and the chemical interface plasmon damping where the conduction electrons are
      transferred across the metal-metal interface. In addition, a pronounced red shift
      due to the Ti adhesion layer, more than predicted using electromagnetic
      simulation, suggests the prevalence of interfacial reactions. By extending the
      experiment to conductively coupled ring-rod nanostructures, it is shown that a
      sharp Fano-like resonance feature is smeared out due to the Ti layer.
      Alternatively, vapor deposition of (3-mercaptopropyl)trimethoxysilane on gently
      cleaned and activated lithographic patterns functionalizes the glass surface
      sufficiently to link the gold nanostructures to the surface by sulfur-gold
      chemical bonds without observable plasmon damping effects.

PMID- 22646821
TI  - An exploration of patient-reported symptoms in systemic lupus erythematosus and
      the relationship to health-related quality of life.
AB  - OBJECTIVE: The aim of this study was to explore the most distressing symptoms of
      systemic lupus erythematosus (SLE) and determine how these relate to health
      related quality of life (HRQoL), anxiety/depression, patient demographics, and
      disease characteristics (duration, activity, organ damage). METHODS: In a cross
      sectional study, patients with SLE (n = 324, age 18-84 years) gave written
      responses regarding which SLE-related symptoms they experienced as most
      difficult. Their responses were categorized. Within each category, patients
      reporting a specific symptom were compared with non-reporters and analysed for
      patient demographics, disease duration, and results from the following
      questionnaires: the Medical Outcomes Study 36-item Short Form Health Survey (SF
      36), the Hospital Anxiety and Depression Scale (HADS), the Systemic Lupus
      Activity Measure (SLAM), the SLE Disease Activity Index (SLEDAI), and the
      Systemic Lupus International Collaboration Clinics/American College of
      Rheumatology (SLICC/ACR) damage index. RESULTS: Twenty-three symptom categories
      were identified. Fatigue (51%), pain (50%), and musculoskeletal distress (46%)
      were most frequently reported. Compared with non-reporters, only patients
      reporting fatigue showed a statistically significant impact on both mental and
      physical components of HRQoL. Patients with no present symptoms (10%) had higher
      HRQoL (p < 0.001) and lower levels of depression (p < 0.001), anxiety (p < 0.01),
      and disease activity (SLAM) (p < 0.001). CONCLUSION: Fatigue, pain, or
      musculoskeletal distress dominated the reported symptoms in approximately half of
      the patients. Only patients reporting fatigue scored lower on both mental and
      physical aspects of HRQoL. Our results emphasize the need for further support and
      interventions to ease the symptom load and improve HRQoL in patients with SLE.
      Our findings further indicate that this need is particularly urgent for patients
      with symptoms of pain or fatigue.

PMID- 22646822
TI  - Resonantly enhanced multiphoton ionization and zero kinetic energy photoelectron
      spectroscopy of chrysene: a comparison with tetracene.
AB  - We report the electronic and vibrational spectroscopy of chrysene using
      resonantly enhanced multiphoton ionization (REMPI) and zero kinetic energy (ZEKE)
      photoelectron spectroscopy. As an isomer of tetracene, chrysene contains a kink
      in the middle of the four fused hexagonal rings, which complicates not just the
      symmetry but, more importantly, the molecular orbitals and hence vibronic
      transitions. Incidentally, the two nearby electronically excited states of
      chrysene have the same symmetry, and vibronic coupling introduces no out-of-plane
      vibrational modes. As a result, the REMPI spectrum of chrysene contains
      essentially only in-plane ring deformation modes, similar to that of tetracene.
      However, density functional calculations using gaussian even after the inclusion
      of vibronic coupling can only duplicate the observed REMPI spectrum in a
      qualitative sense, and the agreement is considerably worse than our recent work
      on a few pericondensed polycyclic aromatic hydrocarbons and on tetracene. The
      ZEKE spectrum of chrysene via the origin band of the intermediate electronic
      state S(1), however, can be qualitatively reproduced by a straightforward Franck
      Condon calculation. The ZEKE spectra from vibrationally excited states of the
      S(1), on the other hand, demonstrate some degree of mode selectivity: the overall
      intensity of the ZEKE spectrum can vary by an order of magnitude depending on the
      vibrational mode of the intermediate state. A scaling factor in the theoretical
      vibrational frequency for the cation is also needed to compare with the
      experimental result, unlike tetracene and pentacene.

PMID- 22646823
TI  - Mapping of pharmacological space.
AB  - The analysis of pharmacological space is becoming highly relevant in light of the
      emerging polypharmacology paradigm, that is, the increasing evidence that many
      drugs elicit therapeutic effects and adverse drug reactions through interactions
      with multiple targets. To better understand desired and undesired
      polypharmacology and identify new targets for existing drugs, computational
      methods are of critical importance. Herein we provide an overview of
      computational approaches for analyzing pharmacological space and put their
      opportunities and limitations in perspective. Insights into computational
      approaches for the study of target-ligand interactions and polypharmacology are
      provided and put into scientific context. The interplay between computational and
      experimental approaches is rationalized. Computational methods have become
      indispensable tools for the systematic analysis of drug-target interactions.
      Because currently most prominent predictive methods are knowledge-based, they are
      affected by data bias and sparseness. Predictions of drug-target interactions are
      already carried out on a large scale, but experimentally validated to a much
      lesser extent. In order to demonstrate true utility of pharmacological space
      analysis for drug discovery, it will be essential to closely interface
      computational and experimental target profiling efforts.

PMID- 22646824
TI  - Harnessing the power of genomics and immunoinformatics to produce improved
      vaccines.
AB  - The role of cellular immunity as a mediator of protection against disease is
      gaining recognition, particularly with regard to the many pathogens for which we
      presently lack effective vaccines. As a result, there is an ever-increasing need
      to understand the T-cell populations induced by vaccination and, therefore, T
      cell epitopes responsible for triggering their activation. Although the
      characterization and harnessing of cellular immunity for vaccine development is
      an active area of research interest, the field still needs to rigorously define T
      cell epitope specificities, above all, on a genomic level. New immunoinformatic
      epitope mapping tools now make it possible to identify pathogen epitopes and
      perform comparisons against human and microbial genomic data sets. Such
      information will help to determine whether adaptive immune responses elicited by
      a vaccine are both pathogen-specific and protective, but not crossreactive
      against host or host-associated sequences that could jeopardize self-tolerance
      and/or human microbiome-host homeostasis. Here, we discuss advances in genomics
      and vaccine design and their relevance to the development of safer, more
      effective vaccines.

PMID- 22646825
TI  - Recent developments of transgenic and xenograft mouse models of pancreatic cancer
      for translational research.
AB  - IMPORTANCE OF THE FIELD: Pancreatic cancer is a devastating disease associated
      with near uniform mortality. Usually diagnosed at advanced, metastatic stages
      when surgical resection with curative intention is not possible any more, most
      patients succumb to progressive disease after a few months. Despite recent
      advances in understanding pancreatic carcinogenesis and continuous efforts in
      translational research, so far these results failed to translate into clinically
      relevant improvements of patient survival. AREAS COVERED IN THIS REVIEW:
      Preclinical evaluation of drug candidates and novel therapeutic strategies rely
      on in vitro and in vivo model systems to predict response in patients. This
      article reviews mouse models of pancreatic cancer, their respective applications
      in translational research and discusses their potential to predict clinical
      responses in patients. WHAT THE READER WILL GAIN: This article provides a
      profound overview of individual strength as well as of shortcomings of mouse
      models of pancreatic cancer currently available for translational research. TAKE
      HOME MESSAGE: Considerable progress in designing mouse models of pancreatic
      cancer has been made over the last decade and several xenograft as well as
      genetically engineered mouse models faithfully recapitulating human disease
      development has been developed. Taken together, these newly developed in vivo
      model systems provide powerful tools likely to boost preclinical evaluation and
      bench-to-bedside transition of novel therapeutic approaches directed against this
      dire malady.

PMID- 22646826
TI  - Preclinical drug development for childhood cancer.
AB  - IMPORTANCE OF THE FIELD: More effective drugs are needed to treat poor prognosis
      paediatric malignancies. Development of anticancer agents for childhood cancers
      faces several unique challenges compared with their adult counterparts. AREAS
      COVERED IN THIS REVIEW: We demonstrate how recent advances in preclinical drug
      development may overcome these difficulties and challenges. We explain the role
      of academia, regulators and industry in this field, address issues with
      preclinical models and illustrate several examples of biology-driven drug
      development in childhood cancers. WHAT THE READER WILL GAIN: Increased knowledge
      about preclinical drug development in paediatric oncology including different
      preclinical models, established preclinical research networks, and relationships
      among academia, industry and regulators, as illustrated by several examples of
      targeted agents in childhood solid malignancies. TAKE HOME MESSAGE: It is
      anticipated that emerging advanced preclinical models and testing platforms will
      provide a more efficient, biologically-driven rationale to support the use of
      targeted therapies in several malignancies such as neuroblastoma, medulloblastoma
      or high grade glioma which account for the majority of deaths related to
      childhood cancer.

PMID- 22646827
TI  - Accounting for water molecules in drug design.
AB  - IMPORTANCE OF THE FIELD: Water molecules often appear around ligands in protein
      crystal structures. Reliable prediction of the effects of water on ligand binding
      remains a challenge. Solvation effects are crucial for lead optimization where a
      100-fold difference in binding affinity is significant but correspond to only ~3
      kcal/mol in binding free energy. Well-known examples, such as nonpeptidic urea
      inhibitors of HIV protease, prove that careful examination of water molecules and
      their energetics can contribute significantly to a successful drug design
      campaign. AREAS COVERED IN THIS REVIEW: In this review, we examine methods to
      account for the effect of water in ligand binding at two stages of drug
      discovery: lead identification via docking calculations and lead optimization. We
      provide a survey of the models and techniques available to account for water in
      drug design. WHAT THE READER WILL GAIN: The reader will become aware of common
      practices and pitfalls in dealing with water molecules in structure-based drug
      design. TAKE HOME MESSAGE: Although solvation effects are not fully understood,
      some pragmatic recommendations at the end of the article provide guidance for
      modelers in this area as well as new practitioners.

PMID- 22646828
TI  - Strategies for the discovery of anti-aging compounds.
AB  - IMPORTANCE OF THE FIELD: Life expectancy has increased across the globe and the
      number of aged people is increasing rapidly. With the rise in the average age of
      people, the prevalence of age related pathologies has also increased and thus the
      strategies to find anti-aging molecules assume significance. Anti-aging basically
      concerns the prevention or delaying the alterations taking place as a function of
      age which are manifested as age-associated illnesses. AREAS COVERED IN THIS
      REVIEW: This review covers anti-aging strategies involving supplementation of
      dietary antioxidants such as polyphenols, vitamins E and C, lipoic acid, acetyl
      carnitine, carnosine and cysteine along with the application of mammalian target
      of rapamycin inhibitors and plasma membrane redox system activators. It also
      presents the use of different hormone supplementation, for example, melatonin,
      dehydroepiandrosterone, growth hormone and sex hormones as a tool against aging.
      The use of caloric restriction and calorie restriction mimetics as an anti-aging
      intervention is also reviewed. WHAT THE READER WILL GAIN: The concept, use and
      efficacy of different anti-aging approaches. TAKE HOME MESSAGE: Despite a lot of
      research and sustained ongoing efforts, finding a viable anti-aging therapy which
      can extend the maximum human lifespan remains elusive. However, several
      interventions aimed towards a longer healthy life seem promising.

PMID- 22646829
TI  - Unilateral seminoma in a dromedary camel.
AB  - A 10-year-old, clinically healthy, male dromedary camel had presented a history
      of progressive unilateral testicular enlargement over the past 5 years. The
      animal had mated with 32 females during that period; all had conceived. The sex
      ratio of his offspring was one male to 31 females. Ultrasound examination of the
      right testicle revealed a diffusely heterogeneous parenchyma with no identifiable
      normal testicular tissue. The enlarged testicle was surgically removed.
      Macroscopically, the testicle had a glistening pink surface and contained
      multiple soft, bulging nodules. Histopathologically, a well-differentiated,
      diffuse seminoma was diagnosed. In conclusion, this study describes the
      fertility, sex ratio, clinical findings and ultrasonographic imaging in a male
      dromedary camel affected with unilateral testicular seminoma.

PMID- 22646830
TI  - Using an in vitro model of lipid deposition to assess the efficiency of hydrogen
      peroxide solutions to remove lipid from various contact lens materials.
AB  - PURPOSE: To test the ability of two commercially available hydrogen peroxide
      disinfection solutions, one containing a surfactant and one without, to remove
      lipid from various contact lens materials using in vitro radiochemical
      experiments. METHODS: Etafilcon A, senofilcon A and balafilcon A contact lens
      materials were incubated in an artificial tear solution (ATS) containing a
      mixture of lipids, proteins, mucin and either (14)C-cholesterol or (14)C
      phosphatidylcholine for 8 h. Following incubation, the lenses were removed,
      rinsed, and placed for 16 h in either a surfactant-containing peroxide solution
      (ClearCare(r)), a peroxide solution devoid of a surfactant (AOSept(r)) or stored
      without solution (control). This process was repeated every day for 1 week. The
      lenses were extracted with a previously optimized extraction protocol,
      evaporated, re-suspended, fluor added and counted for their radioactive signals.
      Masses of lipids deposited were calculated based on standard calibration curves,
      the disinfection solutions were compared and repeated measures ANOVA and post hoc
      statistical analysis was completed using Statistica 9. RESULTS: The results of
      this experiment found that daily disinfection with hydrogen peroxide solutions
      reduced the amount of cholesterol and phosphatidylcholine deposited on the three
      contact lens materials examined, however in many cases the reduction in
      deposition was less than 15% when compared to the control. Disinfection with the
      solution containing the surfactant (ClearCare), resulted in the least deposited
      cholesterol and phosphatidylcholine for all materials, however not all of the
      comparisons were statistically significant. CONCLUSIONS: Overall, ClearCare
      hydrogen peroxide disinfection solution containing Pluronic 17R4 removed the most
      lipid from lenses when compared to the non-surfactant containing AOSept or the
      control, for both lipids and all lens materials. However, the differences found
      were quite small at times and whether these differences are clinically
      significant are yet to be determined.

PMID- 22646831
TI  - Fifty years of Weibel-Palade bodies: the discovery and early history of an
      enigmatic organelle of endothelial cells.
AB  - In 1962, a rod-shaped cytoplasmic organelle of endothelial cells, later called
      the Weibel-Palade body, was serendipitously discovered by electron microscopy. It
      contains a set of parallel tubules and is wrapped in a membrane. Subsequent
      studies in the following decades established the unique localization of this
      organelle in endothelial cells of all vertebrates studied, meaning that it could
      serve as a marker of endothelial cells in tissue cultures. However, these studies
      did not reveal its functional significance, except for an indication that it
      could be related to an undefined thromboplastic substance. Twenty years after its
      discovery as a structural entity, it was shown by others that it houses von
      Willebrand factor and is thus clearly related to the coagulation system. In this
      review, I provide a personal historical account of the discovery and the
      subsequent limited work that I carried out on the organelle, putting it in the
      perspective of the current state of knowledge after half a century of research by
      many scientists.

PMID- 22646833
TI  - Novel analysis of clinically relevant diagnostic errors in point-of-care devices:
      a rebuttal.

PMID- 22646832
TI  - Comparison of the Villalta post-thrombotic syndrome score in the ipsilateral vs.
      contralateral leg after a first unprovoked deep vein thrombosis.
AB  - BACKGROUND: Post-thrombotic syndrome (PTS) is the most frequent complication of a
      deep vein thrombosis (DVT). International guidelines recommend assessing PTS with
      the Villalta scale, a clinical measure that incorporates venous symptoms and
      signs in the leg ipsilateral to a DVT. However, these signs and symptoms are not
      specific for PTS and their prevalence and relevance in the contralateral leg have
      not previously been studied. METHODS: Using data from the REVERSE prospective
      multicentre cohort study, we compared the Villalta total score and prevalence of
      venous signs and symptoms in the ipsilateral vs. contralateral leg in patients
      with a first, unilateral DVT 5 to 7 months previously. RESULTS: Among the 367
      patients analyzed, the mean Villalta score was higher in the ipsilateral than in
      the contralateral leg (mean +/- standard deviation [SD] 3.7 [3.4] vs. 1.9 [2.5],
      respectively; P<0.0001). Villalta scores in the ipsilateral and contralateral
      legs were strongly correlated (r=0.68; P<0.0001). Ipsilateral PTS (defined by a
      Villalta total score >4) was present in 31.6% (n=116) of patients. Among these,
      39.7% (n=46) of patients had a Villalta score >4 in the contralateral leg, and
      the distribution of Villalta symptoms and signs components was similar between
      the legs. CONCLUSIONS: Villalta scores in the ipsilateral and contralateral legs
      are strongly correlated. Almost half of cases considered to be PTS might reflect
      pre-existing symptomatic chronic venous disease. Alternatively, patients with pre
      existing chronic venous disease might be more prone to developing PTS after a
      DVT. Performing a bilateral assessment of Villalta scores at the acute phase of
      DVT could be of clinical interest from a diagnostic, prognostic and therapeutic
      point of view.

PMID- 22646836
TI  - Reliable determination of amidicity in acyclic amides and lactams.
AB  - Two independent computational methods have been used for determination of amide
      resonance stabilization and amidicities relative to N,N-dimethylacetamide for a
      wide range of acyclic and cyclic amides. The first method utilizes carbonyl
      substitution nitrogen atom replacement (COSNAR). The second, new approach
      involves determination of the difference in amide resonance between N,N
      dimethylacetamide and the target amide using an isodesmic trans-amidation process
      and is calibrated relative to 1-aza-2-adamantanone with zero amidicity and N,N
      dimethylacetamide with 100% amidicity. Results indicate excellent coherence
      between the methods, which must be regarded as more reliable than a recently
      reported approach to amidicities based upon enthalpies of hydrogenation. Data for
      acyclic planar and twisted amides are predictable on the basis of the degrees of
      pyramidalization at nitrogen and twisting about the C-N bonds. Monocyclic lactams
      are predicted to have amidicities at least as high as N,N-dimethylacetamide, and
      the beta-lactam system is planar with greater amide resonance than that of N,N
      dimethylacetamide. Bicyclic penam/em and cepham/em scaffolds lose some amidicity
      in line with the degree of strain-induced pyramidalization at the bridgehead
      nitrogen and twist about the amide bond, but the most puckered penem system still
      retains substantial amidicity equivalent to 73% that of N,N-dimethylacetamide.

PMID- 22646835
TI  - Bench and mathematical modeling of the effects of breathing a helium/oxygen
      mixture on expiratory time constants in the presence of heterogeneous airway
      obstructions.
AB  - BACKGROUND: Expiratory time constants are used to quantify emptying of the lung
      as a whole, and emptying of individual lung compartments. Breathing low-density
      helium/oxygen mixtures may modify regional time constants so as to redistribute
      ventilation, potentially reducing gas trapping and hyperinflation for patients
      with obstructive lung disease. In the present work, bench and mathematical models
      of the lung were used to study the influence of heterogeneous patterns of
      obstruction on compartmental and whole-lung time constants. METHODS: A two
      compartment mechanical test lung was used with the resistance in one compartment
      held constant, and a series of increasing resistances placed in the opposite
      compartment. Measurements were made over a range of lung compliances during
      ventilation with air or with a 78/22% mixture of helium/oxygen. The resistance
      imposed by the breathing circuit was assessed for both gases. Experimental
      results were compared with predictions of a mathematical model applied to the
      test lung and breathing circuit. In addition, compartmental and whole-lung time
      constants were compared with those reported by the ventilator. RESULTS: Time
      constants were greater for larger minute ventilation, and were reduced by
      substituting helium/oxygen in place of air. Notably, where time constants were
      long due to high lung compliance (i.e. low elasticity), helium/oxygen improved
      expiratory flow even for a low level of resistance representative of healthy,
      adult airways. In such circumstances, the resistance imposed by the external
      breathing circuit was significant. Mathematical predictions were in agreement
      with experimental results. Time constants reported by the ventilator were well
      correlated with those determined for the whole-lung and for the low-resistance
      compartment, but poorly correlated with time constants determined for the high
      resistance compartment. CONCLUSIONS: It was concluded that breathing a low
      density gas mixture, such as helium/oxygen, can improve expiratory flow from an
      obstructed lung compartment, but that such improvements will not necessarily
      affect time constants measured by the ventilator. Further research is required to
      determine if alternative measurements made at the ventilator level are predictive
      of regional changes in ventilation. It is anticipated that such efforts will be
      aided by continued development of mathematical models to include pertinent
      physiological and pathophysiological phenomena that are difficult to reproduce in
      mechanical test systems.

PMID- 22646837
TI  - Adaptation of an osmotically pumped continuous in situ water sampler for
      application in riverine environments.
AB  - We present the design of an osmotic water sampler that is adapted to and
      validated in freshwater. The sample is drawn into and stored in a continuous
      narrow bore tube. This geometry and slow pump rate (which is temperature
      dependent: 0.8 mL/d at 4  degrees C to 2.0 mL/d at 28  degrees C) minimizes
      sample dispersion. We have implemented in situ time-stamping which enables
      accurate study of pump rates and sample time defining procedures in field
      deployments and comparison with laboratory measurements. Temperature variations
      are common in rivers, and without an accurate time-stamping, or other defining
      procedure, time of sampling is ambiguous. The sampler was deployed for one month
      in a river, and its performance was evaluated by comparison with manually
      collected samples. Samples were analyzed for major ions using Ion Chromatography
      and collision reaction Inductively Couple Mass Spectrometry. Despite the
      differences of the two sampling methods (osmotic sampler averages, while manual
      samples provide snapshots), the two data sets show good agreement (average R(2) ~
      0.7), indicating the reliability of the sampler and at the same time highlighting
      the advantages of high frequency sampling in dynamic environments.

PMID- 22646838
TI  - Four-state folding of a SH3 domain: salt-induced modulation of the stabilities of
      the intermediates and native state.
AB  - Unstable intermediates on the folding pathways of proteins can be stabilized
      sufficiently so that they accumulate to detectable extents by the addition of a
      suitable cosolute. Here, the effect of sodium sulfate (Na(2)SO(4)) on the folding
      of the SH3 domain of PI3 kinase was investigated in the presence of guanidine
      hydrochloride  (GdnHCl) using intrinsic tyrosine fluorescence and 1
      anilinonaphthalene-8-sulfonate (ANS) binding. The free energy of unfolding in
      water of the native state (N) increases linearly with Na(2)SO(4) concentration,
      indicating stabilization via the Hofmeister effect. The addition of 0.5 M
      Na(2)SO(4) causes accumulation of an early intermediate L, which manifests itself
      as (1) a sub-millisecond change in tyrosine and ANS fluorescence and (2) a
      curvature in the chevron plot. It is shown that L is a specific structural
      component of the initially collapsed ensemble. An intermediate, M, also
      accumulates in unfolding studies conducted in the presence of 0.5 M Na(2)SO(4)
      and manifests itself by causing a curvature in the unfolding arm of the chevron.
      M is shown to be a wet molten globule that binds to ANS under unfolding
      conditions and is stabilized to the same extent as N in the presence of
      Na(2)SO(4). A four-state U <-> L <-> M <-> N scheme satisfactorily modeled the
      kinetic data. Thus, the folding of the PI3K SH3 domain in the presence of salt
      commences via the formation of a structured intermediate ensemble L, which
      accumulates before the rate-limiting step of folding. L subsequently proceeds to
      N via the late intermediate M that forms after the rate-limiting transition of
      folding.

PMID- 22646839
TI  - Diastereo- and enantioselective synthesis of (E)-2-Methyl-1,2-syn- and (E)-2
      Methyl-1,2-anti-3-pentenediols via allenylboronate kinetic resolution with
      ((d)Ipc)2BH and aldehyde allylboration.
AB  - Enantioselective hydroboration of racemic allenylboronate (+/-)-1 with 0.48 equiv
      of ((d)Ipc)(2)BH at -25  degrees C proceeds with efficient kinetic resolution and
      provides allylborane (R)-Z-4. When heated to 95  degrees C, allylborane (R)-Z-4
      isomerizes to the thermodynamically more stable allylborane isomer (S)-E-7.
      Subsequent allylboration of aldehydes with (R)-Z-4 or (S)-E-7 at -78  degrees C
      followed by oxidative workup provides 1,2-syn- or 1,2-anti-diols, 2 or 3,
      respectively, in 87-94% ee.

PMID- 22646840
TI  - Gluten sensitivity and veterinary medicine.

PMID- 22646841
TI  - Investigation of serum amino acid and serum amyloid A concentrations in chickens
      with amyloid arthropathy.
AB  - BACKGROUND: Increased proteolytic cleavage of serum amyloid A (SAA) may
      potentially contribute to the development of AA amyloid deposition. OBJECTIVE: To
      study the possible relationship between amyloid artropathy and expression of SAA
      and some serum amino acids. ANIMALS AND METHODS: Values of 15 serum amino acids
      and SAA were investigated in chickens with experimentally induced amyloid
      arthropathy. Thirty-four, 5-week-old chicks were allocated into two groups: one
      group was injected intra-articularly with 0.25 mL complete Freund's adjuvant at
      the left tibio-metatarsal joint to induce amyloid arthropathy, whereas the other
      group served as control. All pullets were necropsied 13 weeks after injection.
      Collected tissue samples were examined histopathologically. Blood samples were
      collected and SAA concentrations were measured with enzyme-linked immunosorbent
      assay. High-performance liquid chromatography was used to assess the amino acid
      concentrations in serum. RESULTS: Amyloid accumulation in joints occurred only in
      the experimental group (89%). SAA concentrations of 166 +/- 17 and 423 +/- 39
      (SD) ng/mL were found in the control and experimental groups, respectively (p <
      0.001). In the experimental group, an increase was observed in all examined amino
      acid concentrations except for citrulline. The most significant (p < 0.001)
      increases were noticed in serine (from 159 +/- 15 to 360 +/- 29 umol/L), glycine
      (from 151 +/- 20 to 279 +/- 16 umol/L), isoleucine (from 48 +/- 2 to 80 +/- 6
      umol/L), and phenylalanine (from 49 +/- 2 to 90 +/- 3 umol/L). CONCLUSION: The
      results of this study suggest that there is a positive correlation between some
      serum amino acid values, especially serine, glycine, isoleucine, and
      phenylalanine, and the high concentrations of SAA in chickens with amyloid
      arthropathy.

PMID- 22646842
TI  - Therapeutic options to decrease actinic keratosis and squamous cell carcinoma
      incidence and progression in solid organ transplant recipients: a practical
      approach.
AB  - BACKGROUND: Solid organ transplant recipients (SOTRs) have a 50 to 250 times
      greater risk of squamous cell carcinoma (SCC) than the general population and
      experience higher rates of invasive and metastatic disease. These greater risks
      are a product of the tumorigenic effects of their immunosuppressive medications.
      As the number of transplantations and the life expectancy of SOTRs increase, SCCs
      are becoming a major source of morbidity and mortality. OBJECTIVE: To present a
      practical approach for busy practicing clinicians to the care of SOTRs who are
      developing SCCs. Topics include assessment and treatment of new and neglected
      SOTRs; the dermatologist's role with the transplantation team; and practical
      considerations in the choice of topical agents, systemic agents, and
      immunosuppressive therapy manipulation. METHODS AND MATERIALS: An extensive
      literature search of the understanding of SCC pathophysiology and treatment in
      SOTRs was conducted. RESULTS: Presented here is a logical, concise guide to the
      care of SOTRs who are developing actinic keratoses and SCCs. CONCLUSION: Proper
      assessment of patients, understanding therapeutic alternatives and their
      application, and early institution of preventative and adjuvant therapies can
      help to decrease skin cancer-related morbidity and mortality in SOTRs.

PMID- 22646843
TI  - Consumer perspectives about weight management services in a community pharmacy
      setting in NSW, Australia.
AB  - BACKGROUND: Obesity is a public health challenge faced worldwide. Community
      pharmacists may be well placed to manage Australia's obesity problem owing to
      their training, accessibility and trustworthiness. However, determining
      consumers' needs is vital to the development of any new services or the
      evaluation of existing services. OBJECTIVE: To explore Australian consumers'
      perspectives regarding weight management services in the community pharmacy
      setting, including their past experiences and willingness to pay for a specific
      pharmacy-based service. DESIGN: An online cross-sectional consumer survey was
      distributed through a marketing research company. The survey instrument comprised
      open-ended and closed questions exploring consumers' experiences of and
      preferences for weight management services in pharmacy. It also included an
      attitudinal measure, the Consumer Attitude to Pharmacy Weight Management Services
      (CAPWMS) scale. SETTING AND PARTICIPANTS: A total of 403 consumers from New South
      Wales, Australia, completed the survey. RESULTS: The majority of respondents had
      previously not sought a pharmacist's advice regarding weight management. Those
      who had previously consulted a pharmacist were more willing to pay for and
      support pharmacy-based services in the future. Most consumers considered
      pharmacists' motivations to provide advice related to gaining profit from selling
      a product and expressed concerns about the perceived conflicts of interest.
      Participants also perceived pharmacists as lacking expertise and time.
      CONCLUSION: Although Australian consumers were willing to seek pharmacists'
      advice about weight management, they perceived several barriers to the provision
      of weight management services in community pharmacy. If barriers are addressed,
      community pharmacies could be a viable and accessible setting to manage obesity.

PMID- 22646844
TI  - New insights into the pathology of white matter tracts in cerebral palsy from
      diffusion magnetic resonance imaging: a systematic review.
AB  - AIM: Structural connectivity analysis using diffusion magnetic resonance imaging
      (dMRI) and tractography has become the method of choice for studying white matter
      pathology and reorganization in children with congenital hemiplegia. To evaluate
      its role in the research domain, we systematically reviewed the literature about
      children with cerebral palsy (CP) to document common findings and identify
      strengths and possible limitations of this neuroimaging technology. METHOD: A
      literature search was performed for peer-reviewed studies pertaining to dMRI and
      CP. RESULTS: Twenty-two studies met the inclusion criteria. The corticospinal
      tract was studied in greatest detail (18/22). The most common finding was
      decreased fractional anisotropy and/or increased mean diffusivity, indicating
      significant loss in the integrity of these corticomotor pathways. Fewer studies
      assessed ascending sensorimotor pathways including the posterior and superior
      thalamic radiations, which also showed decreased fractional anisotropy.
      Anisotropy indices (fractional anisotropy, mean diffusivity) obtained for both
      corticomotor and sensorimotor tracts were repeatedly shown to correlate with
      clinical measures. Other tracts studied included commissural and association
      fibres, which showed conflicting results. INTERPRETATION: There is sound evidence
      that dMRI-based connectivity techniques are useful for improving our
      understanding of the structure-function relationships of corticomotor and
      sensorimotor neural networks in CP.

PMID- 22646845
TI  - Direct visualization of transient thermal response of a DNA origami.
AB  - The DNA origami approach enables the construction of complex objects from DNA
      strands. A fundamental understanding of the kinetics and thermodynamics of DNA
      origami assembly is extremely important for building large DNA structures with
      multifunctionality. Here both experimental and theoretical studies of DNA origami
      melting were carried out in order to reveal the reversible
      association/disassociation process. Furthermore, by careful control of the
      temperature cycling via in situ thermally controlled atomic force microscopy, the
      self-assembly process of a rectangular DNA origami tile was directly visualized,
      unveiling key mechanisms underlying their structural and thermodynamic features.

PMID- 22646846
TI  - Identification of chemosensory receptor genes in Manduca sexta and knockdown by
      RNA interference.
AB  - BACKGROUND: Insects detect environmental chemicals via a large and rapidly
      evolving family of chemosensory receptor proteins. Although our understanding of
      the molecular genetic basis for Drosophila chemoreception has increased
      enormously in the last decade, similar understanding in other insects remains
      limited. The tobacco hornworm, Manduca sexta, has long been an important model
      for insect chemosensation, particularly from ecological, behavioral, and
      physiological standpoints. It is also a major agricultural pest on solanaceous
      crops. However, little sequence information and lack of genetic tools has
      prevented molecular genetic analysis in this species. The ability to connect
      molecular genetic mechanisms, including potential lineage-specific changes in
      chemosensory genes, to ecologically relevant behaviors and specializations in M.
      sexta would be greatly beneficial. RESULTS: Here, we sequenced transcriptomes
      from adult and larval chemosensory tissues and identified chemosensory genes
      based on sequence homology. We also used dsRNA feeding as a method to induce RNA
      interference in larval chemosensory tissues. CONCLUSIONS: We report
      identification of new chemosensory receptor genes including 17 novel odorant
      receptors and one novel gustatory receptor. Further, we demonstrate that systemic
      RNA interference can be used in larval olfactory neurons to reduce expression of
      chemosensory receptor transcripts. Together, our results further the development
      of M. sexta as a model for functional analysis of insect chemosensation.

PMID- 22646847
TI  - Efficacy of olanzapine long-acting injection in patients with acutely exacerbated
      schizophrenia: an insight from effect size comparison with historical oral data.
AB  - BACKGROUND: To treat acute schizophrenia, a long-acting injectable antipsychotic
      needs a rapid onset of action and therapeutic profile similar to that of oral
      agents. The present post-hoc analyses compared results from a randomized, double
      blind, placebo-controlled trial of olanzapine long-acting injection (LAI) for
      acute schizophrenia with those observed in similarly designed trials of oral
      olanzapine. METHODS: Six-week results from the olanzapine LAI study (N = 404)
      were compared with those of 3 oral studies (study 1: olanzapine vs. haloperidol
      vs. placebo [N = 335]; study 2: olanzapine vs. haloperidol vs. low-dose
      olanzapine [N = 431]; study 3: olanzapine vs. placebo vs. low-dose olanzapine [N
      = 152]). All patients had baseline Brief Psychiatric Rating Scale (BPRS) scores
      >=24 (0-6 scale). Six-week effect sizes were calculated. Efficacy onset,
      pharmacokinetics, discontinuations, weight gain, and extrapyramidal symptoms were
      also assessed. RESULTS: At 6 weeks, mean BPRS scores decreased by 14 to 15 points
      for olanzapine LAI (405 mg/4 weeks, 210 or 300 mg/2 weeks), by 8 to 16 for oral
      olanzapine (10 +/- 2.5 or 15 +/- 2.5 mg/day), and by 12 to 13 for haloperidol (15
      +/- 5 mg/day). For those same dose groups, effect sizes vs. placebo for the BPRS
      were 0.7 to 0.8 for olanzapine LAI, 0.5 to 0.7 for oral olanzapine, and 0.6 for
      haloperidol. The first statistically significant separation from placebo on the
      BPRS occurred at 3 days for the olanzapine LAI groups and at 1 week for oral
      olanzapine and haloperidol (15 +/- 5 mg/day) in oral study 1 although as late as
      week 6 for the 10-mg/day olanzapine dose in oral study 3. Olanzapine
      concentrations were similar across studies. Weight gain >=7% of baseline occurred
      in up to 35% of olanzapine LAI and oral patients versus up to 12% of haloperidol
      and placebo patients. Extrapyramidal symptoms were lowest in the olanzapine LAI
      groups and significantly greater in the haloperidol groups. No post-injection
      delirium/sedation syndrome events occurred in the olanzapine LAI study.
      CONCLUSIONS: Patients treated acutely with olanzapine LAI showed a similar
      pattern of improvement to that seen historically with oral olanzapine. With the
      exception of injection-related adverse events, the efficacy and tolerability
      profile of olanzapine LAI is similar to oral olanzapine. TRIAL REGISTRATION:
      ClinicalTrials.gov ID; URL: http://http//www.clinicaltrials.gov/: NCT00088478;
      ClinicalStudyResults.org ID; URL: http://www.clinicalstudyresults.org/: 917, 978,
      982, and 5984.

PMID- 22646848
TI  - A mHealth cardiac rehabilitation exercise intervention: findings from content
      development studies.
AB  - BACKGROUND: Involving stakeholders and consumers throughout the content and study
      design ensures interventions are engaging and relevant for end-users. The aim of
      this paper is to present the content development process for a mHealth (mobile
      phone and internet-based) cardiac rehabilitation (CR) exercise intervention.
      METHODS: An innovative mHealth intervention was developed with patient input
      using the following steps: conceptualization, formative research, pre-testing,
      and pilot testing. Conceptualization, including theoretical and technical
      aspects, was undertaken by experts. For the formative component, focus groups and
      interviews with cardiac patients were conducted to discuss their perceptions of a
      mHealth CR program. A general inductive thematic approach identified common
      themes. A preliminary library of text and video messages were then developed.
      Participants were recruited from CR education sessions to pre-test and provide
      feedback on the content using an online survey. Common responses were extracted
      and compiled. An iterative process was used to refine content prior to pilot
      testing and conduct of a randomized controlled trial. RESULTS: 38 CR patients and
      3 CR nurses participated in the formative research and 20 CR patients
      participated in the content pre-testing. Participants perceived the mHealth
      program as an effective approach to inform and motivate patients to exercise. For
      the qualitative study, 100% (n = 41) of participants thought it to be a good
      idea, and 11% of participants felt it might not be useful for them, but would be
      for others. Of the 20 participants who completed the online survey, 17 out of 20
      (85%) stated they would sign up to a program where they could receive information
      by video messages on a website, and 12 out of 20 (60%) showed interest in a
      texting program. Some older CR patients viewed technology as a potential barrier
      as they were unfamiliar with text messaging or did not have mobile phones. Steps
      to instruct participants to receive texts and view the website were written into
      the study protocol. Suggestions to improve videos and wording of texts were fed
      back to the content development team and refined. CONCLUSIONS: Most participants
      thought a mHealth exercise program was an effective way to deliver exercise-based
      CR. The results were used to develop an innovative multimedia exercise
      intervention. A randomized controlled trial is currently underway. TRIAL
      REGISTRATION: ACTRN12611000117910.

PMID- 22646850
TI  - Proteomic analysis of hepatitis C virus (HCV) core protein transfection and host
      regulator PA28gamma knockout in HCV pathogenesis: a network-based study.
AB  - Hepatitis C virus (HCV) causes chronic liver disease worldwide. HCV Core protein
      (Core) forms the viral capsid and is crucial for HCV pathogenesis and HCV-induced
      hepatocellular carcinoma, through its interaction with the host factor proteasome
      activator PA28gamma. Here, using BD-PowerBlot high-throughput Western array, we
      attempt to further investigate HCV pathogenesis by comparing the protein levels
      in liver samples from Core-transgenic mice with or without the knockout of
      PA28gamma expression (abbreviated PA28gamma(-/-)CoreTG and CoreTG, respectively)
      against the wild-type (WT). The differentially expressed proteins integrated into
      the human interactome were shown to participate in compact and well-connected
      cellular networks. Functional analysis of the interaction networks using a newly
      developed data warehouse system highlighted cellular pathways associated with
      vesicular transport, immune system, cellular adhesion, and cell growth and death
      among others that were prominently influenced by Core and PA28gamma in HCV
      infection. Follow-up assays with in vitro HCV cell culture systems validated
      VTI1A, a vesicular transport associated factor, which was upregulated in CoreTG
      but not in PA28gamma(-/-)CoreTG, as a novel regulator of HCV release but not
      replication. Our analysis provided novel insights into the Core-PA28gamma
      interplay in HCV pathogenesis and identified potential targets for better anti
      HCV therapy and potentially novel biomarkers of HCV infection.

PMID- 22646851
TI  - Babesia microti in rodents and raccoons from northeast Florida.
AB  - Human babesiosis in the United States is caused most commonly by the
      intraerythrocytic protozoan parasite, Babesia microti . Although a few reports
      have described evidence of Babesia species in animals in Florida, to date Babesia
      microti specifically has not been reported from Florida or most other southern
      states. To determine if the organism is present in vertebrates in the region,
      small mammals were trapped and sampled at 2 sites in northeastern Florida, and
      DNA extracts from blood samples were screened for B. microti DNA via PCR assays
      targeting portions of the nuclear small subunit rRNA (18S rDNA) and beta-tubulin
      genes. Amplified fragments from representative samples of PCR-positive hosts were
      sequenced and compared phylogenetically to reference strains of Babesia species.
      The B. microti strains found in cotton rats ( Sigmodon hispidus ) most closely
      resembles B. microti sensu stricto strains that are pathogenic to humans, and
      strains found in raccoons ( Procyon lotor ) most closely resembles previously
      described raccoon-related strains of B. microti sensu lato. The results of this
      study suggest that B. microti is prevalent among cotton rats and raccoons at some
      sites in northeast Florida and may pose a risk to humans in the region.

PMID- 22646852
TI  - Why older patients of lower clinical urgency choose to attend the emergency
      department.
AB  - BACKGROUND/AIMS: To examine non-clinical factors associated with emergency
      department (ED) attendance by lower urgency older patients. METHODS: An
      exploratory descriptive study comprising structured interviews with lower urgency
      community-dwelling patients aged >=70 years presenting to a tertiary metropolitan
      Melbourne public hospital ED. Demographical and clinical characteristics, self
      reported feelings of social connectedness, perceived accessibility to primary
      care, reason for attending ED were measured. RESULTS: One hundred patients were
      interviewed: mean age 82 years, 56% female, 57% lived alone; 73% presented during
      business hours, 58% arrived by ambulance, 80% presented for illness, and 65% were
      discharged home within 48 h. Fifty-six per cent of patients reported feeling
      socially disconnected, comprising 49% living alone compared with 65% who lived
      with their spouse/family. All patients attended a regular general practitioner,
      31% reporting regular review appointments. Thirty-five per cent reported waiting
      times >2-3 days for urgent problems; 59% stated accessing care 'after hours'
      without attending ED as difficult, with 20% having attended ED 3-6 times in the
      previous 12 months. Reasons for attending ED were referral by a third party,
      difficulty with accessibility to primary care, patient preferences for timely
      care and fast-track access to specialist care. CONCLUSIONS: Most older patients
      of lower clinical urgency presented to ED because of perceived access block to
      primary or specialist services, alongside an expectation of more timely and
      specialised care. This suggests that EDs should be redesigned and/or integrated
      community-based models of care developed to meet the specific needs of this age
      group who have growing demand for acute care.

PMID- 22646853
TI  - Fall prevention using olfactory stimulation with lavender odor in elderly nursing
      home residents: a randomized controlled trial.
AB  - OBJECTIVES: To investigate the effects of lavender olfactory stimulation
      intervention on fall incidence in elderly nursing home residents. DESIGN:
      Randomized placebo-controlled trial. SETTING: Three randomly selected nursing
      homes in northern Japan. PARTICIPANTS: One hundred and forty-five nursing home
      residents aged 65 and older. INTERVENTION: Participants were randomly assigned to
      the lavender (n = 73) or placebo group (n = 72) for a 360-day study period. The
      lavender group received continuous olfactory stimulation from a lavender patch.
      The placebo group received an unscented patch. MEASUREMENT: The primary outcome
      measure was resident falls. Other measurements taken at baseline and 12 months
      included functional ability (assessed using the Barthel Index), cognitive
      function (Mini-Mental State Examination (MMSE)), and behavioral and psychological
      problems associated with dementia (Cohen-Mansfield Agitation Inventory (CMAI)).
      RESULTS: There were fewer fallers in the lavender group (n = 26) than in the
      placebo group (n = 36) (hazard ratio (HR)=0.57, 95% confidence interval (CI) =
      0.34-0.95) and a lower incidence rate in the lavender group (1.04 per person
      year) than in the placebo group (1.40 per person-year) (incidence rate ratio =
      0.51, 95% CI = 0.30-0.88). The lavender group also had a significant decrease in
      CMAI score (P = .04) from baseline to follow-up in a per protocol analysis.
      CONCLUSION: Lavender olfactory stimulation may reduce falls and agitation in
      elderly nursing home residents; further research is necessary to confirm these
      findings.

PMID- 22646854
TI  - Resistance to high-maintenance dose of prasugrel treated by ticagrelor: a case
      report.
AB  - We describe a case of a 34-year-old woman with chronic renal failure under
      haemodialysis. The patient exhibited high on-treatment platelet reactivity to
      gradually stronger thienopyridine regimens, including standard and high
      maintenance doses of prasugrel. Platelet function was monitored by VerifyNow
      assay and genotyping for various single-nucleotide polymorphisms was performed.
      Treatment with ticagrelor 180 mg/day was effective in reducing the platelet
      reactivity.

PMID- 22646855
TI  - Assessment of body fluid status in hemodialysis patients using the body
      composition monitor measurement technique.
AB  - AIMS AND OBJECTIVES: The main objective of the study was to correlate the target
      dry weight in haemodialysis (HD) patients as assessed clinically by nephrologists
      to those measured by the Body Composition Monitor (BCM - Fresenius) machine. The
      second objective was to compare pre and postdialysis changes of extracellular
      fluid and clinical parameters. BACKGROUND: Clinical assessment of target dry
      weight in HD patients remains problematic. Inaccurate dry weight resulted in
      hypovolaemic or overhydration states. The BCM (Fresenius) utilises bioimpedance
      technology for body fluid monitoring and has been extensively validated. DESIGN:
      This was a prospective cross-sectional study on consecutive patients who
      underwent HD and gave informed consent. Methods.  The target dry weights of these
      patients were first assessed by their attending nephrologists and appropriate
      ultrafiltration prescribed. Their body fluid statuses were then measured with the
      BCM before and after HD treatment. RESULTS: Eighty HD patients (37 men, 43 women)
      with a mean age of 55 +/- 13 years and a mean duration on HD of 71 +/- 56 months
      were studied. The dry weight measured by BCM significantly correlated with dry
      weight assessed by the nephrologists. The mean dry weight was higher when
      assessed by the nephrologists compared to that by BCM. Only systolic blood
      pressure and not other components of blood pressure reduced after HD treatments.
      CONCLUSION: The BCM is a rapid and easy-to-use tool that can help HD nursing
      staffs to adjust patients' dry weights between nephrologists' reviews thus
      optimising HD therapy and patient outcomes. RELEVANCE TO CLINICAL PRACTICE: We
      propose that experienced HD nursing staff be trained in the use of the BCM or
      other simple bioimpedance machines to help monitor patient overhydration and
      approximate dry weight in consultation with the nephrologists responsible for the
      care of these patients so as to obviate excessive residual overhydration between
      nephrology reviews.

PMID- 22646856
TI  - Chronic lymphocytic leukemia specific T-cell subset alterations are clone-size
      dependent and not present in monoclonal B lymphocytosis.
AB  - In patients with chronic lymphocytic leukemia (CLL), effector and memory CD4 +
      and CD8 + T cells are expanded. We investigated whether these CLL specific T-cell
      expansions also occur in monoclonal B lymphocytosis (MBL), the pre-leukemic state
      of CLL, which is currently distinguished from CLL by an arbitrarily chosen cut
      off value of CD19 of 5.0 * 10(9)/L. Whereas an increase in effector and memory
      CD4 + and CD8 + T cells was found in CLL, these expansions could not be found in
      MBL. Although a significant correlation was found between absolute B cell count
      (CD19) and T cell numbers, correlation coefficients were rather low. Therefore,
      we analyzed whether an optimal threshold for CD19 number could be defined which
      best related to an expansion of T cells. The B-cell threshold that best predicted
      expansion of CD3 +, CD4 + and CD8 + T cells, respectively, was 10 * 10(9)/L. Our
      study indicates that a higher cut-off value than the current 5.0 * 10(9)/L
      relates better to the biological impact of CLL.

PMID- 22646857
TI  - Enhanced thrombin generation and depressed anticoagulant function in children
      with pneumonia.
AB  - AIMS: To clarify the status of the coagulation system in children with community
      acquired pneumonia. METHODS: Coagulation activation markers (prothrombin fragment
      F1 + 2, thrombin-antithrombin complexes, D-dimer), the natural anticoagulants
      (antithrombin, protein C and S) and tissue factor were measured in 28 consecutive
      children with pneumonia on admission to the hospital. Patients were divided into
      those with either bacterial-type pneumonia (at least two of the following three
      criteria: plasma C-reactive protein (CRP) >80 mg/L, white blood cell count >15 *
      10(9) /L and alveolar infiltrates on the chest radiograph) or viral-type
      pneumonia. RESULTS: The majority of the patients (79%) showed elevation of at
      least one of the three coagulation activation markers. Plasma CRP concentration
      correlated with F1 + 2 (R = 0.44, p < 0.05) and D-dimer (R = 0.71, p < 0.0001).
      Patients with bacterial-type pneumonia (n = 17) had higher D-dimer levels (p <
      0.05) and lower levels of antithrombin (p = 0.005) and protein C (p = 0.08) than
      the patients with viral-type pneumonia. CONCLUSIONS: Children with community
      acquired bacterial-type pneumonia show distinctive changes in their coagulation
      system. The finding of coagulation system activation and depressed function of
      natural anticoagulants in uncomplicated pneumonia helps to understand the rapid
      and unpredictable changes observed in the coagulation status in patients with
      more severe forms of disease.

PMID- 22646859
TI  - Computational approaches for drug target identification in pathogenic diseases.

PMID- 22646858
TI  - Comprehensive data-driven analysis of the impact of chemoinformatic structure on
      the genome-wide biological response profiles of cancer cells to 1159 drugs.
AB  - BACKGROUND: Detailed and systematic understanding of the biological effects of
      millions of available compounds on living cells is a significant challenge. As
      most compounds impact multiple targets and pathways, traditional methods for
      analyzing structure-function relationships are not comprehensive enough.
      Therefore more advanced integrative models are needed for predicting biological
      effects elicited by specific chemical features. As a step towards creating such
      computational links we developed a data-driven chemical systems biology approach
      to comprehensively study the relationship of 76 structural 3D-descriptors
      (VolSurf, chemical space) of 1159 drugs with the microarray gene expression
      responses (biological space) they elicited in three cancer cell lines. The
      analysis covering 11350 genes was based on data from the Connectivity Map. We
      decomposed the biological response profiles into components, each linked to a
      characteristic chemical descriptor profile. RESULTS: Integrated analysis of both
      the chemical and biological space was more informative than either dataset alone
      in predicting drug similarity as measured by shared protein targets. We
      identified ten major components that link distinct VolSurf chemical features
      across multiple compounds to specific cellular responses. For example, component
      2 (hydrophobic properties) strongly linked to DNA damage response, while
      component 3 (hydrogen bonding) was associated with metabolic stress. Individual
      structural and biological features were often linked to one cell line only, such
      as leukemia cells (HL-60) specifically responding to cardiac glycosides.
      CONCLUSIONS: In summary, our approach identified several novel links between
      specific chemical structure properties and distinct biological responses in cells
      incubated with these drugs. Importantly, the analysis focused on chemical
      biological properties that emerge across multiple drugs. The decoding of such
      systematic relationships is necessary to build better models of drug effects,
      including unanticipated types of molecular properties having strong biological
      effects.

PMID- 22646860
TI  - Monitoring Gq-coupled receptor response through inositol phosphate quantification
      with the IP-One assay.
AB  - INTRODUCTION: G-protein-coupled receptors (GPCRs) are transmembrane proteins that
      play a key role in the signal transduction of extracellular stimuli. GPCRs
      associate to a complex assembly of intracellular proteins regulating a large
      variety of signaling pathways. In particular, the production of inositol 1,4,5
      triphosphate (IP3) signs the activation of Gq-coupled receptors. However, its
      very short half-life makes its assessment too challenging for drug screening
      operations and the monitoring of calcium release, triggered by IP3, has been
      extensively used as a downstream readout of this signaling pathway. Recently, a
      new homogeneous time-resolved fluorescence (HTRF) assay, detecting a downstream
      metabolite of IP3, inositol monophosphate (IP1), has overcome the drawbacks of
      the IP3 quantification, allowing its use in primary or secondary screening. AREAS
      COVERED: This review provides an overview of the use of the IP-One assay in
      screening processes, providing comparisons with results obtained with other
      existing techniques traditionally used to investigate Gq-coupled receptors.
      Moreover, the review highlights two key features of the IP-One assay, the
      discrimination of slow acting compounds and the characterization of inverse
      agonists, which are impossible to achieve using calcium release. EXPERT OPINION:
      The IP-One assay is well established to perform screening in the pharmaceutical
      industry. A number of criteria can be taken into account, including the impact of
      the sensitivity improvement of the assay, to position the IP-One assay in the
      different stages of the drug screening process. Moreover, the IP-One assay can be
      used as a valuable solution to investigate new research concepts such as ligand
      biased signaling or receptor heteromerization.

PMID- 22646861
TI  - Cannabinoid 1 G protein-coupled receptor (periphero-)neutral antagonists:
      emerging therapeutics for treating obesity-driven metabolic disease and reducing
      cardiovascular risk.
AB  - INTRODUCTION: Obesity and related cardiometabolic derangements are spiraling
      global health problems urgently in need of safe, effective and durable
      pharmacotherapy. AREAS COVERED: As an orexigenic and anabolic biosignaling
      network, the endocannabinoid system interacts with other information-transducing
      pathways to help ensure metabolic homeostasis. Hyperphagia stimulates reinforcing
      neuronal circuits favoring energy intake and conservation, inviting
      overweight/obesity and cardiometabolic risk factors ('metabolic syndrome').
      Associated increases in cannabinoid 1 G protein-coupled receptor (CB1R)
      activity/expression further exacerbate food consumption and the metabolic shift
      toward fat production and accumulation. The role of CB1R activity in hyperphagia
      and weight gain spurred the development of rimonabant (SR141716; Acomplia), the
      first-in-class CB1R antagonist/inverse agonist weight-loss drug. Rimonabant and
      similar CB1R inverse agonists also exert pleiotropic actions in addition to
      weight-loss effects that help correct obesity-related metabolic derangements and
      reduce cardiovascular risk in humans. The medicinal utility of these agents was
      crippled by clinically significant central and peripheral adverse effects that
      appear to reflect CB1R inverse agonists as a class. Consequently, increased
      attention is being given to CB1R neutral antagonists, CB1R blockers with
      intrinsically weak, if any, functional potency to elicit the negative-efficacy
      responses associated with inverse agonists. Laboratory studies demonstrate that
      CB1R neutral antagonists - whether readily accessible to the central nervous
      system or not (i.e., 'periphero-neutral' antagonists) - retain the salient
      therapeutic effects of CB1R inverse agonists on hyperphagia, weight-gain, and
      obesity-driven metabolic abnormalities with the distinct advantage of being
      associated with significantly less preclinical adverse events than are
      conventional CB1R inverse agonists such as rimonabant. EXPERT OPINION: CB1R
      (periphero-)neutral antagonists merit continued analysis of their molecular
      pharmacology and evaluation of their therapeutic significance and translational
      potential as new-generation medicines for obesity-related derangements, including
      nonalcoholic fatty liver disease and type 2 diabetes, if not obesity itself.

PMID- 22646862
TI  - Identifying and testing potential new anti-asthma agents.
AB  - INTRODUCTION: Inhaled corticosteroids alone or with long-acting beta-2 agonists
      (LABA) are the basic treatment for stable asthma. While the majority of patients
      are controllable, some patients retain chronic severe disease and develop
      permanent alterations in airway function. For patients such as these it is
      important to better understand the mechanisms of asthma so that alternative
      approaches can be developed. AREA COVERED: Based on data from in vitro cell
      culture, animal models and clinical trials, this review discusses potential
      agents targeting either key effector cells, mediators and their receptors in
      asthma pathogenesis or their signaling cascade molecules. EXPERT OPINION: As
      targeting single Th2 cytokines and their receptors has been shown to have limited
      clinical benefit, it is important to identify and test potential new therapeutic
      agents. Recent studies suggest that blockade of IgE synthesis, its interaction
      with its receptors and downstream signaling, identification of molecular targets
      in innate immune and airways structural cells, and fresh anti-neutrophil
      strategies should be prominent among these. Further studies are required to
      clarify the relationship between airways remodeling and asthma severity so that
      appropriate patients may be targeted.

PMID- 22646863
TI  - The design of semi-synthetic and synthetic glycoconjugate vaccines.
AB  - INTRODUCTION: Glycoconjugate vaccines are among the safest and most efficacious
      vaccines developed during the last 30 years. They are a potent tool for
      prevention of life-threatening bacterial infectious diseases like meningitis and
      pneumonia. The concept of hapten-carrier conjugation is now being extended to
      other disease areas. AREAS COVERED: This is an overview of the history and
      current status of glycoconjugate vaccines. The authors discuss the approaches for
      their preparation and quality control as well as those variables which might
      affect their product profile. The authors also look at the potential to develop
      fully synthetic conjugate vaccines based on the progress of organic chemistry.
      Additionally, new applications of conjugate vaccines technology in the field of
      non-infectious diseases are discussed. Through this review, the reader will have
      an insight regarding the issues and complexities involved in the preparation and
      characterization of conjugate vaccines, the variables that might affect their
      immunogenicity and the potential for future applications. EXPERT OPINION: The
      immunogenicity of weak T-independent antigens can be increased in quantity and
      quality by conjugation to protein carriers, which provide T-cell help.
      Glycoconjugate vaccines are among the safest and most efficacious vaccines
      developed so far. Various conjugation procedures and carrier proteins can be
      used. Many variables impact on the immunogenicity of conjugate vaccines and a
      tight control through physicochemical tests is important to ensure manufacturing
      and clinical consistency. New and challenging targets for conjugate vaccines are
      represented by cancer and other non-infectious diseases.

PMID- 22646864
TI  - The successes and failures of HIV drug discovery.
AB  - INTRODUCTION: To date, several anti-human immunodeficiency virus (HIV) drugs,
      including reverse transcriptase inhibitors and protease inhibitors, have been
      developed and used clinically for the treatment of patients infected with HIV.
      Recently, novel drugs have been discovered which have different mechanisms of
      action from those of the above inhibitors, including entry inhibitors and
      integrase (IN) inhibitors; the clinical use of three of these inhibitors has been
      approved. Other inhibitors are still in development. AREAS COVERED: This review
      article summarizes the history of the development of anti-HIV drugs and also
      focuses on successes in the development of these entry and IN inhibitors, along
      with looking at exploratory approaches for the development of other inhibitors.
      EXPERT OPINION: Currently used highly active antiretroviral therapy can be
      subject to a loss of efficacy, due to the emergence of multi-drug resistant (MDR)
      strains; a change of regimens of the drug combination is required to combat this,
      along with careful monitoring of the virus and CD4 in the blood, by methods such
      as cellular tropism testing. In such a situation, entry inhibitors such as
      CCR5/CXCR4 antagonists, CD4 mimics, fusion inhibitors and IN inhibitors might be
      optional agents for an expansion of the drug repertoire available to patients at
      all stages of HIV infection.

PMID- 22646865
TI  - New approaches for pediatric rhabdomyosarcoma drug discovery: targeting
      combinatorial signaling.
AB  - INTRODUCTION: Rhabdomyosarcomas (RMS) are rare heterogeneous pediatric tumors
      that are treated by surgery, chemotherapy and irradiation. New therapeutic
      approaches are needed, especially in the advanced stages to target the pro
      oncogenic signals. Exploring the molecular interactions of the regulatory signals
      and their roles in the developmental aspects of different subtypes of RMS is
      essential to identify potential targets and develop new therapeutic drugs. AREAS
      COVERED: Insights into different drug discovery approaches are discussed with
      specific emphasis on gene expression profiling, fusion protein, role of small
      interfering RNA (siRNA)- and microRNA (miRNA)-based discovery approaches,
      targeting cancer stem cells, and in vitro and in vivo model systems. Targeting
      some overexpressed signals along with the possibilities of combination therapy of
      validated drug targets is discussed. Additionally, methods to overcome the
      limitations of discovery-based research are briefly discussed. EXPERT OPINION:
      Due to drug resistance, ineffective therapy in advanced stages and relapse, there
      is a demand to explore new drug targets and discovery approaches. Implementing
      miRNA-based profiling would reveal the extent of miR-based regulation, various
      biomarkers and potential targets in RMS. A suitable combination of innovative
      techniques and the use of model systems might assist the identification and
      validation of novel targets and drug discovery methods. Combining specific drugs
      along with type-specific target inhibition of overexpressed mRNAs through siRNA
      approaches would enable the development of personalized therapy.

PMID- 22646866
TI  - Effect of very early treatment in rheumatoid arthritis on bone oedema and
      synovitis, using magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the magnetic resonance imaging (MRI) findings of hand
      involvement before and 1 year after treatment in patients with early rheumatoid
      arthritis (RA). METHOD: MRI of the dominant hand was performed in 22 patients
      fulfilling the new criteria for early RA. The patients were divided into three
      groups. Nine had very early RA (VERA; disease duration < 3 months), seven had
      early RA (ERA; disease duration < 6 months), and six had established RA (ESTRA;
      disease duration > 12 months). The MRI protocol consisted of fat-suppressed T2,
      and plain and contrast-enhanced T1-weighted sequences. Assessment of bone marrow
      oedema, synovitis, and bone erosions was performed by the OMERACT RA MRI scoring
      system. Patients were treated with methotrexate (MTX) 0.2 mg/kg/body weight/week
      and prednisone 7.5 mg/day. Clinical assessment was evaluated using the Disease
      Activity Score for 28 joint indices (DAS28). RESULTS: After treatment, a
      significant decrease was observed: (a) in DAS28 of VERA (6.2 +/- 0.9 vs. 2.4 +/-
      1.2), ERA (5.3 +/- 0.8 vs. 2.8 +/- 1.0), and ESTRA patients (5.7 +/- 8.0 vs. 2.7
      +/- 0.7; p < 0.05); (b) in bone oedema (16.77 +/- 13.78 vs. 5.88 +/- 6.31) and
      synovitis (12.44 +/- 6.44 vs. 2.88 +/- 3.25) of VERA patients; and (c) in
      synovitis (7.57 +/- 6.32 vs. 1.42 +/- 1.81) of ERA patients (p < 0.05). No
      significant difference was found in erosions in any group. CONCLUSION: Bone
      marrow oedema and synovitis decrease significantly when RA is diagnosed and
      treated early. MRI is useful in the early detection of these changes. MTX
      treatment resulted in a significant decrease in DAS28 score and significant
      improvement in bone oedema and synovitis.

PMID- 22646867
TI  - Single-step assembly of cationic lipid-polymer hybrid nanoparticles for systemic
      delivery of siRNA.
AB  - The clinical success of therapeutics of small interfering RNA (siRNA) is still
      hindered by its delivery systems. Cationic polymer or lipid-based vehicles as the
      major delivery systems of siRNA cannot sufficiently satisfy siRNA therapeutic
      applications. It is hypothesized that cationic lipid-polymer hybrid nanoparticles
      may take advantage of both polymeric and lipid-based nanoparticles for siRNA
      delivery, while diminishing the shortcomings of both. In this study, cationic
      lipid-polymer hybrid nanoparticles were prepared by a single-step
      nanoprecipitation of a cationic lipid (N,N-bis(2-hydroxyethyl)-N-methyl-N-(2
      cholesteryloxycarbonyl aminoethyl) ammonium bromide, BHEM-Chol) and amphiphilic
      polymers for systemic delivery of siRNA. The formed hybrid nanoparticles
      comprised a hydrophobic polylactide core, a hydrophilic poly(ethylene glycol)
      shell, and a cationic lipid monolayer at the interface of the core and the shell.
      Such hybrid nanoparticles exhibited excellent stability in serum and showed
      significantly improved biocompatibility compared to that of pure BHEM-Chol
      particles. The hybrid nanoparticles were capable of delivering siRNA into BT474
      cells and facilitated the escape of loaded siRNA from the endosome into the
      cytoplasm. The hybrid nanoparticles carrying polo-like kinase 1 (Plk1)-specific
      siRNA (siPlk1) remarkably and specifically downregulated expression of the
      oncogene Plk1 and induced cancer cell apoptosis both in vitro and in vivo and
      significantly suppressed tumor growth following systemic administration. We
      demonstrate that this system is stable, nontoxic, highly efficient, and easy to
      scale up, bringing the clinical application of siRNA therapy one important step
      closer to reality.

PMID- 22646870
TI  - Swan song.

PMID- 22646868
TI  - Mead CompuChem(r).

PMID- 22646871
TI  - EPA's fiscal 1983 budget.

PMID- 22646873
TI  - The foxboro company.

PMID- 22646872
TI  - Nuclear waste disposal.

PMID- 22646874
TI  - Bird cover.

PMID- 22646875
TI  - Response to Dr. Riordan's rebuttal.

PMID- 22646876
TI  - Washington.

PMID- 22646877
TI  - Science.

PMID- 22646878
TI  - Technology.

PMID- 22646879
TI  - States.

PMID- 22646880
TI  - Industry.

PMID- 22646881
TI  - Racal-decca survey, inc.

PMID- 22646882
TI  - The marine environment.

PMID- 22646883
TI  - Beckman.

PMID- 22646885
TI  - American chemical society publications.

PMID- 22646884
TI  - Herbicides in agriculture.

PMID- 22646886
TI  - Biggs moves on.

PMID- 22646887
TI  - Comtex scientific corporation.

PMID- 22646888
TI  - Today, trade publications available to.

PMID- 22646890
TI  - Fugacity revisited.

PMID- 22646889
TI  - Nuclear waste disposal.

PMID- 22646891
TI  - Products.

PMID- 22646892
TI  - Literature.

PMID- 22646894
TI  - Based on a symposium jointly sponsored.

PMID- 22646895
TI  - International.

PMID- 22646897
TI  - The pesticide chemist and modern toxicology.

PMID- 22646898
TI  - Courses.

PMID- 22646899
TI  - professional consulting services directory.

PMID- 22646900
TI  - Classified section.

PMID- 22646901
TI  - Index to the advertisers in this issue.

PMID- 22646902
TI  - Taking things apart & putting things together.

PMID- 22646903
TI  - Computations of 36 tautomer/isomer equilibria of different lactams.
AB  - Gas-phase energies of 36 tautomer/isomer pairs of 18 six-membered N-heterocyclic
      compounds were computed quantum chemically. Among the considered B3LYP, BH&HLYP,
      BH&HLYP(G), and PW6B95 DFT functionals, the latter two provide accurate
      tautomer/isomer pair energies with root-mean-square deviations (rmsd) relative to
      experiments of 0.2 and 0.3 kcal/mol, respectively. Since only few (namely five)
      experimental data are available, 15 tautomer/isomer pair energies were computed
      with the very precise QCISD(T)(quadruple-zeta) method serving as reference.
      Relative to this reference the PW6B95 DFT functional is slightly superior to the
      BH&HLYP(G) functional, yielding an rmsd of 0.7 and 0.8 kcal/mol, respectively. In
      contrast to BH&HLYP(G), the PW6B95 DFT functional yields also accurate
      tautomer/isomer pair energies if zwitterionic structures are involved. The
      tautomer/isomer pair states possess different amounts of aromaticity. This is
      characterized by nucleus-independent chemical shift (NICS) values. The
      tautomer/isomer pair reference energies, from which the energies computed with
      PW6B95 are subtracted, correlate linearly with the corresponding differences in
      the NICS values. This correlation is used to construct a correction term for the
      pair energies computed with PW6B95, yielding tautomer/isomer pair energies with
      rmsd of 0.3 kcal/mol with respect to the more CPU time demanding
      QCISD(T)(quadruple-zeta) method.

PMID- 22646904
TI  - The EGFR tyrosine kinase inhibitor tyrphostin AG-1478 causes hypomagnesemia and
      cardiac dysfunction.
AB  - We determined whether the epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor (TKI) N-(3-chlorophenyl)-6,7-dimethoxy-4-quinazolinamine (tyrphostin AG
      1478) causes hypomagnesemia and cardiac dysfunction in rats. Tyrphostin was
      administered (3 times per week, intraperitoneal injection, to achieve 21.4 mg.(kg
      body mass)(-1).day(-1)) to normomagnesemic rats for 5 weeks. Levels of magnesium
      in the plasma of the tyrphostin-treated rats decreased significantly by the
      following amount: 17% at week 1, 27% at week 2, and 26%-35% between weeks 3 to 5.
      Levels of the plasma lipid peroxidation marker 8-isoprostane rose significantly:
      by 58% at week 1, 168% at week 3, and 113% at week 5. At week 5, blood
      neutrophils from the tyrphostin-treated group displayed a 2.26-fold higher basal
      level of O(2)(.-) generation; the ratio of oxidized glutathione (glutathione
      disulfide; GSSG) to reduced glutathione (GSH) in the red blood cells increased
      2.5-fold. At week 5, echocardiography revealed that TKI treatment resulted in
      significant cardiac systolic dysfunction, with impaired diastolic function and
      dilated cardiomyopathy. Since hypomagnesemia alone can trigger oxidative stress
      and cardiac injury, we suggest that inhibition of EGFR-TK caused magnesium
      wasting, which partly contributed to decreased cardiac contractility.

PMID- 22646905
TI  - Identification and characterization of pig embryo microRNAs by Solexa sequencing.
AB  - MicroRNAs (miRNAs) are a class of small, non-coding RNAs of approximately 22
      nucleotides in length that regulate gene expression by binding to the 3'
      untranslated regions of target mRNAs. It is now clear that miRNAs are involved in
      many biological processes, including proliferation, differentiation and
      regulation of gene expression during early embryonic development. The miRBase
      16.0 (2010) shows that there are 175, 673, 408 and 1048 annotated miRNAs for
      Caenorhabditis elegans, Mus musculus, Rattus norvegicus and Homo sapiens,
      respectively. However, there are only 211 miRNAs described for Sus scrofa. In
      particular, the full set of miRNAs and their expression patterns are still poorly
      understood in the embryo. Therefore, we combined Solexa sequencing with
      computational techniques to analyse the sequences and relative expression levels
      of S. scrofa miRNAs at embryonic day 33 (E33). Of the distinct miRNAs identified,
      76 previously known miRNAs and 194 candidate miRNAs were identified in head, and
      77 known miRNAs and 130 predicted candidate miRNAs were identified in organ
      region. Furthermore, we performed additional investigation for identifying the
      potential target mRNAs using PicTar and TargetScan. Concurrent function analysis
      suggested that highly expressed miRNAs are mostly involved in the development of
      nerves, cerebrum, muscle and organs. Our results provide useful information for
      the investigation into embryonic miRNAs of pig and provide a valuable resource
      for investigators interested in the regulation of embryonic development in pigs
      and other animals.

PMID- 22646907
TI  - An algorithm for management of deep brain stimulation battery replacements:
      devising a web-based battery estimator and clinical symptom approach.
AB  - OBJECTIVE: Deep brain stimulation (DBS) is an effective technique that has been
      utilized to treat advanced and medication-refractory movement and psychiatric
      disorders. In order to avoid implanted pulse generator (IPG) failure and
      consequent adverse symptoms, a better understanding of IPG battery longevity and
      management is necessary. BACKGROUND: Existing methods for battery estimation lack
      the specificity required for clinical incorporation. Technical challenges prevent
      higher accuracy longevity estimations, and a better approach to managing end of
      DBS battery life is needed. METHODS: The literature was reviewed and DBS battery
      estimators were constructed by the authors and made available on the web at
      http://mdc.mbi.ufl.edu/surgery/dbs-battery-estimator. A clinical algorithm for
      management of DBS battery life was constructed. The algorithm takes into account
      battery estimations and clinical symptoms. RESULTS: Existing methods of DBS
      battery life estimation utilize an interpolation of averaged current drains to
      calculate how long a battery will last. Unfortunately, this technique can only
      provide general approximations. There are inherent errors in this technique, and
      these errors compound with each iteration of the battery estimation. Some of
      these errors cannot be accounted for in the estimation process, and some of the
      errors stem from device variation, battery voltage dependence, battery usage,
      battery chemistry, impedance fluctuations, interpolation error, usage patterns,
      and self-discharge. We present web-based battery estimators along with an
      algorithm for clinical management. We discuss the perils of using a battery
      estimator without taking into account the clinical picture. CONCLUSION: Future
      work will be needed to provide more reliable management of implanted device
      batteries; however, implementation of a clinical algorithm that accounts for both
      estimated battery life and for patient symptoms should improve the care of DBS
      patients.

PMID- 22646906
TI  - Association of rs2072183 SNP and serum lipid levels in the Mulao and Han
      populations.
AB  - BACKGROUND: Niemann-pick C1-like 1 (NPC1L1) is a key protein for intestinal
      cholesterol transportation. Common single nucleotide polymorphisms (SNPs) in the
      NPC1L1 gene have been associated with cholesterol absorption and serum lipid
      levels. The present study was undertaken to explore the possible association of
      NPC1L1 rs2072183 1735 C > G SNP and several environmental factors with serum
      lipid levels in the Mulao and Han populations. METHODS: Genotyping of the
      rs2072183 SNP was performed in 688 subjects of Mulao and 738 participants of Han
      Chinese. The interactions between NPC1L1 1735 C > G polymorphism and several
      environmental factors on serum lipid phenotypes were tested using the factorial
      design covariance analysis after controlling for potential confounders. RESULTS:
      The frequency of G allele was lower in Mulao than in Han (29.72% vs. 37.26%, P <
      0.001). The frequency of CC, CG and GG genotypes was 49.85%, 40.84% and 9.31% in
      Mulao, and 39.30%, 46.88% and 13.82% in Han (P < 0.001); respectively. The levels
      of low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) B and the
      ratio of ApoAI/ApoB in Han but not in Mulao were different among the three
      genotypes (P < 0.05 for all), the subjects with GG and CG genotypes had higher
      LDL-C, ApoB levels and lower ApoAI/ApoB ratio than the subjects with CC genotype.
      Subgroup analysis showed that the G allele carriers in Han had higher total
      cholesterol (TC), LDL-C and ApoB levels in males (P < 0.05) and lower ApoAI/ApoB
      ratio in both sexes (P < 0.05) than the G allele noncarriers. The G allele
      carriers in Mulao had higher TC and LDL-C levels in males (P < 0.05) and lower
      high-density lipoprotein cholesterol (HDL-C) levels in both sexes (P < 0.05) than
      the G allele noncarriers. Serum TC, LDL-C, ApoB levels and ApoAI/ApoB ratio were
      correlated with genotypes in Han males (P < 0.05) but not in females. Serum lipid
      parameters were also correlated with several environmental factors. The genotypes
      of rs2072183 SNP were interacted with gender or cigarette smoking to influence
      serum TC and HDL-C levels in Mulao, whereas the genotypes of rs2072183 SNP were
      interacted with several environmental factors to influence all seven lipid traits
      in Han (P < 0.05-0.01). CONCLUSIONS: The present study suggests that the
      rs2072183 SNP in NPC1L1 gene and its association with serum lipid profiles are
      different between the Mulao and Han populations. The difference in serum lipid
      profiles between the two ethnic groups might partly result from different
      rs2072183 SNP or NPC1L1 gene-environmental interactions.

PMID- 22646908
TI  - Intraspecific variability of the essential oil of Calamintha nepeta subsp. nepeta
      from Southern Italy (Apulia).
AB  - The essential oil of 46 spontaneous plants of Calamintha nepeta (L.) Savi subsp.
      nepeta growing wild in Sud, Italy (Salento, Apulia), were investigated by GC/MS.
      Fifty-seven components were identified in the oil representing over the 98% of
      the total oil composition. Four chemotypes were identified: piperitone oxide,
      piperitenone oxide, piperitone-menthone and pulegone.

PMID- 22646909
TI  - A new stereocontrolled synthetic route to (-)-echinosporin from D-glucose via
      Padwa allenylsulfone [3 + 2]-anionic cycloadditive elimination.
AB  - A new formal total synthesis of (-)-echinosporin has been developed based upon
      the Padwa [3 + 2]-cycloadditive elimination reaction of allenylsulfone 4 with the
      D-glucose-derived enone 14 which provides cycloadduct 12.

PMID- 22646910
TI  - Bipolar disorders and Wilson's disease.
AB  - BACKGROUND: The aim of this study was to determine the risk for Bipolar Disorder
      (BD) in Wilson's disease (WD) and to measure the impaired Quality of Life (QL) in
      BD with WD using standardized psychiatric diagnostic tools and a case control
      design. METHODS: This was a case control study. The cases were 23 consecutive
      patients with WD treated at the University Hospital in Cagliari, Italy, and the
      controls were 92 sex- and age-matched subjects with no diagnosis of WD who were
      randomly selected from a database used previously for an epidemiological study.
      Psychiatric diagnoses according to DSM-IV criteria were determined by physicians
      using structured interview tools (ANTAS-SCID). QL was measured by means of SF-12.
      RESULTS: Compared to controls, WD patients had lower scores on the SF-12 and
      higher lifetime prevalence of DSM-IV major depressive disorders (OR = 5.7, 95% CI
      2.4-17.3) and bipolar disorders (OR = 12.9, 95% CI 3.6-46.3). BD was associated
      with lower SF-12 in WD patients. CONCLUSIONS: This study was the first to show an
      association between BD and WD using standardized diagnostic tools and a case
      control design. Reports in the literature about increased schizophrenia-like
      psychosis in WD and a lack of association with bipolar disorders may thus have
      been based on a more inclusive diagnosis of schizophrenia in the past. Our
      findings may explain the frequent reports of loss of emotional control,
      hyperactivity, loss of sexual inhibition, and irritability in WD patients. This
      study was limited by a small sample size.

PMID- 22646911
TI  - Evaluation of the propensity score methods for estimating marginal odds ratios in
      case of small sample size.
AB  - BACKGROUND: Propensity score (PS) methods are increasingly used, even when sample
      sizes are small or treatments are seldom used. However, the relative performance
      of the two mainly recommended PS methods, namely PS-matching or inverse
      probability of treatment weighting (IPTW), have not been studied in the context
      of small sample sizes. METHODS: We conducted a series of Monte Carlo simulations
      to evaluate the influence of sample size, prevalence of treatment exposure, and
      strength of the association between the variables and the outcome and/or the
      treatment exposure, on the performance of these two methods. RESULTS: Decreasing
      the sample size from 1,000 to 40 subjects did not substantially alter the Type I
      error rate, and led to relative biases below 10%. The IPTW method performed
      better than the PS-matching down to 60 subjects. When N was set at 40, the PS
      matching estimators were either similarly or even less biased than the IPTW
      estimators. Including variables unrelated to the exposure but related to the
      outcome in the PS model decreased the bias and the variance as compared to models
      omitting such variables. Excluding the true confounder from the PS model
      resulted, whatever the method used, in a significantly biased estimation of
      treatment effect. These results were illustrated in a real dataset. CONCLUSION:
      Even in case of small study samples or low prevalence of treatment, PS-matching
      and IPTW can yield correct estimations of treatment effect unless the true
      confounders and the variables related only to the outcome are not included in the
      PS model.

PMID- 22646912
TI  - A modest rise of mTWA during HD, which showed a weak correlation with rise of
      heart rate.

PMID- 22646913
TI  - Relation of psychological distress to the international normalized ratio in
      patients with venous thromboembolism with and without oral anticoagulant therapy.
AB  - BACKGROUND: Psychological distress might affect the international normalized
      ratio (INR), but effects might vary depending on oral anticoagulant (OAC)
      therapy. OBJECTIVES: To investigate the association of psychological distress
      with INR and clotting factors of the extrinsic pathway in patients with and
      without OAC therapy. PATIENTS AND METHODS: We studied 190 patients with a
      previous venous thromboembolism (VTE); 148 had discontinued OAC therapy and 42
      had ongoing OAC therapy. To assess psychological distress, all patients completed
      validated questionnaires to measure symptoms of depression, anxiety, worrying,
      anger and hostility. INR, fibrinogen, factor (F)II:C, FV:C, FVII:C and FX:C were
      measured as part of outpatient thrombophilia work-up. RESULTS: In VTE patients
      without OAC therapy, the odds of a reduced INR (< 1.00) were significantly
      increased from 1.5 to 1.8 times for an increase of 1 standard deviation (SD) in
      symptoms of depression, anxiety, worrying and anger, respectively, after
      adjusting for gender, age, body mass index, socioeconomic status, hematocrit and
      C-reactive protein. Worrying, anger and hostility also showed significant direct
      associations with FVII:C. In patients with OAC therapy, INR was unrelated to a
      negative affect; however, lower FVII:C related to anxiety and worrying as well as
      lower FX:C related to anger and hostility were observed in patients with OAC
      therapy compared with those without OAC therapy. CONCLUSIONS: Psychological
      distress was associated with a reduced INR in VTE patients without OAC therapy.
      The direction of the association between psychological distress and activity in
      some clotting factors of the extrinsic coagulation pathway might differ depending
      on whether VTE patients are under OAC therapy or not.

PMID- 22646916
TI  - Crowding alters the folding kinetics of a beta-hairpin by modulating the
      stability of intermediates.
AB  - Crowded environments inside cells exert significant effects on protein structure,
      stability, and function, but their effects on (pre)folding dynamics and kinetics,
      especially at molecular levels, remain ill-understood. Here, we examine the
      latter for, as an initial candidate, a small de novo beta-hairpin using extensive
      all-atom molecular dynamics simulations for crowder volume fractions phi up to
      40%. We find that crowding does not introduce new folding intermediates or
      misfolded structures, although, as expected, it promotes compact structures and
      reduces the accessible conformational space. Furthermore, while hydrophobic
      collapse-mediated folding is slightly enhanced, the turn-directed zipper
      mechanism (dominant in crowder-free situations) increases many-fold, becoming
      even more dominant. Interestingly, phi influences the stability of the folding
      intermediates (FI(1) and FI(2)) in an apparently counterintuitive manner, which
      can be understood only by considering specific intrachain interactions and
      intermediate (and hierarchical) structural transitions. For phi values <20%,
      native-turn formation is enhanced, and FI(1), characterized by a hairpin
      structure but slightly mismatched hydrophobic contacts, increases in frequency,
      thus enhancing eventual folding. However, higher phi values impede native-turn
      formation, and FI(2), which lacks native turns, re-emerges and increasingly acts
      as a kinetic trap. The change in the stability of these intermediates with phi
      strongly correlates with the hierarchical folding stages and their kinetics. The
      results show that crowding assists intermediate structural changes more by
      impeding backward transitions than by promoting forward transitions and that a
      delicate competition between reduction in configuration space and introduction of
      kinetic traps along the folding route is key to understanding folding kinetics
      under crowded conditions.

PMID- 22646917
TI  - Interaction of dopamine transporter (DAT1) genotype and maltreatment for ADHD: a
      latent class analysis.
AB  - BACKGROUND: Although the association of the dopamine transporter (DAT1) gene and
      attention-deficit/hyperactivity disorder (ADHD) has been widely studied, far less
      is known about its potential interaction with environmental risk factors. Given
      that maltreatment is a replicated risk factor for ADHD, we explored the
      interaction between DAT1 and maltreatment with ADHD symptoms defined
      dimensionally and using latent class analysis (LCA). METHOD: We tested the
      association of the 40 base-pair variable number of tandem repeats polymorphism in
      DAT1, maltreatment, and their interaction in 2,488 boys and girls from the
      National Longitudinal Study of Adolescent Health. RESULTS: In boys, ADHD symptoms
      were optimally defined by four classes (Combined, Hyperactive/Impulsive,
      Inattentive, and Normal), whereas in girls, ADHD symptoms were defined by three
      classes (Combined, Combined-Mild, Normal). A significant DAT1 * maltreatment
      interaction revealed that maltreated girls homozygous for the 10-repeat allele
      had more symptoms of ADHD, and were also 2.5 times more likely to be classified
      in the Combined ADHD group than in the Normal Group. CONCLUSIONS: The underlying
      structure of ADHD symptoms differed between boys and girls and DAT1 interacted
      with maltreatment to predict ADHD symptoms and ADHD status derived from LCA.
      Interactive exchanges between maltreatment and DAT1 for ADHD symptoms, and their
      implications for intervention, are discussed.

PMID- 22646918
TI  - Theoretical study on HF elimination and aromatization mechanisms: a case of
      pyridoxal 5' phosphate-dependent enzyme.
AB  - Pyridoxal 5-phosphate (PLP), the phosphorylated and the oxidized form of vitamin
      B6 is an organic cofactor. PLP forms a Schiff base with the epsilon-amino group
      of a lysine residue of PLP-dependent enzymes. gamma-Aminobutyric acid (GABA)
      aminotransferase is a PLP-dependent enzyme that degrades GABA to succinic
      semialdehyde, while reduction of GABA concentration in the brain causes
      convolution besides several neurological diseases. The fluorine-containing
      substrate analogues for the inactivation of the GABA-AT are synthesized
      extensively in cases where the inactivation mechanisms involve HF elimination.
      Although two proposed mechanisms are present for the HF elimination, the details
      of the base-induced HF elimination are not well identified. In this density
      functional theory (DFT) study, fluorine-containing substrate analogue, 5-amino-2
      fluorocyclohex-3-enecarboxylic acid, is particularly chosen in order to explain
      the details of the HF elimination reactions. On the other hand, the experimental
      studies revealed that aromatization competes with Michael addition mechanism in
      the presence of 5-amino-2-fluorocyclohex-3-enecarboxylic acid. The results
      allowed us to draw a conclusion for the nature of HF elimination, besides the
      elucidation of the mechanism preference for the inactivation mechanism.
      Furthermore, the solvent phase calculations carried out in this study ensure that
      the proton transfer steps should be assisted either by a water molecule or a base
      for lower activation energy barriers.

PMID- 22646919
TI  - On defensive decision making: how doctors make decisions for their patients.
AB  - BACKGROUND: In the past decade, the number of lawsuits for medical malpractice
      has risen significantly. This could affect the way doctors make decisions for
      their patients. OBJECTIVE: To investigate whether and why doctors practice
      defensive medicine with their patients. DESIGN: A questionnaire study was
      conducted in general practice departments of eight metropolitan hospitals in
      Spain, between January and February 2010. SETTING AND PARTICIPANTS: Eighty
      general practitioners (48% men; mean age 52 years) with an average of 15.3 years
      of experience and their 80 adult patients (42% men; mean age 56 years)
      participated in the study. MAIN OUTCOME MEASUREMENTS: Participants completed a
      self-administered questionnaire involving choices between a risky and a
      conservative treatment. One group of doctors made decisions for their patients.
      Another group of doctors predicted what their patients would decide for
      themselves. Finally, all doctors and patients made decisions for themselves and
      described the factors they thought influenced their decisions. RESULTS: Doctors
      selected much more conservative medical treatments for their patients than for
      themselves. Most notably, they did so even when they accurately predicted that
      the patients would select riskier treatments. When asked about the reasons for
      their decisions, most doctors (93%) reported fear of legal consequences.
      DISCUSSION AND CONCLUSIONS: Doctors' decisions for their patients are strongly
      influenced by concerns of possible legal consequences. Patients therefore cannot
      blindly follow their doctor's advice. Our study, however, suggests a plausible
      method that patients could use to get around this problem: They could simply ask
      their doctor what he or she would do in the patient's situation.

PMID- 22646921
TI  - Risk factors for birth-related perineal trauma: a cross-sectional study in a
      birth centre.
AB  - AIM AND OBJECTIVES: To identify maternal, newborn and obstetric factors
      associated with birth-related perineal trauma in one independent birth centre.
      BACKGROUND: Risk factors for birth-related perineal trauma include episiotomy,
      maternal age, ethnicity, parity and interventions during labour including use of
      oxytocin, maternal position at time of birth and infant birth weight.
      Understanding more about these factors could support the management of vaginal
      birth to prevent spontaneous perineal trauma, in line with initiatives to reduce
      routine use of episiotomy. DESIGN: Cross-sectional study. METHODS: Data were
      retrospectively collected from one independent birth centre in Brazil, during
      2006-2009. The dependent variable (perineal trauma) was classified as: (1) intact
      perineum or first-degree laceration, (2) second-degree laceration and (3)
      episiotomy (right mediolateral or median). RESULTS: There were 1079 births during
      the study period. Parity, use of oxytocin during labour, position at time of
      giving birth and infant birth weight were associated with second-degree
      lacerations and episiotomies. After adjusting for parity, oxytocin, maternal
      position at the expulsive stage of labour and infant birth weight influenced
      perineal outcomes among primiparae only. CONCLUSIONS: Although the overall rate
      of episiotomies in this study was low compared with national data, it was
      observed that younger women were most vulnerable to this intervention. In this
      age group in particular, the use of oxytocin as well as semi-upright positions at
      the time of birth was associated with second-degree lacerations and episiotomies.
      RELEVANCE TO CLINICAL PRACTICE: The use of upright alternative positions for
      birth and avoidance of use of oxytocin could reduce the risk of perineal trauma
      from lacerations and need to perform episiotomy.

PMID- 22646920
TI  - High-throughput comparison of gene fitness among related bacteria.
AB  - BACKGROUND: The contribution of a gene to the fitness of a bacterium can be
      assayed by whether and to what degree the bacterium tolerates transposon
      insertions in that gene. We use this fact to compare the fitness of syntenic
      homologous genes among related Salmonella strains and thereby reveal differences
      not apparent at the gene sequence level. RESULTS: A transposon Tn5 derivative was
      used to construct mutants in Salmonella Typhimurium ATCC14028 (STM1) and
      Salmonella Typhi Ty2 (STY1), which were then grown in rich media. The locations
      of 234,152 and 53,556 integration sites, respectively, were mapped by sequencing.
      These data were compared to similar data available for a different Ty2 isolate
      (STY2) and essential genes identified in E. coli K-12 (ECO). Of 277 genes
      considered essential in ECO, all had syntenic homologs in STM1, STY1, and STY2,
      and all but nine genes were either devoid of transposon insertions or had very
      few. For three of these nine genes, part of the annotated gene lacked transposon
      integrations (yejM, ftsN and murB). At least one of the other six genes, trpS,
      had a potentially functionally redundant gene encoded elsewhere in Salmonella but
      not in ECO. An additional 165 genes were almost entirely devoid of transposon
      integrations in all three Salmonella strains examined, including many genes
      associated with protein and DNA synthesis. Four of these genes (STM14_1498,
      STM14_2872, STM14_3360, and STM14_5442) are not found in E. coli. Notable
      differences in the extent of gene selection were also observed among the three
      different Salmonella isolates. Mutations in hns, for example, were selected
      against in STM1 but not in the two STY strains, which have a defect in rpoS
      rendering hns nonessential. CONCLUSIONS: Comparisons among transposon integration
      profiles from different members of a species and among related species, all grown
      in similar conditions, identify differences in gene contributions to fitness
      among syntenic homologs. Further differences in fitness profiles among shared
      genes can be expected in other selective environments, with potential relevance
      for comparative systems biology.

PMID- 22646922
TI  - Expression of messenger RNA for transforming growth factor-beta1 and for
      transforming growth factor-beta receptors in peripheral blood of immune
      thrombocytopenic purpura.

PMID- 22646923
TI  - Photodegradable polyurethane self-assembled nanoparticles for photocontrollable
      release.
AB  - Light-responsive drug delivery systems are particularly appealing that are
      capable of releasing active molecules at the appropriate site and rate. We
      synthesized a series of photodegradable polymers that can form nanoparticles for
      drug encapsulation. These particles in aqueous solutions are stable in buffers
      with different pHs or at evaluated temperatures, while light can trigger the
      crash of particles and the release of encapsulated substances. The release
      efficiency can reach up to 90% based on Nile red fluorescence intensity upon 15
      min light irradiation. Nanoparticle uptake by phagocytic cells and light
      triggered release in cells were observed by fluorescence emission of the
      hydrolyzed fluorescein diacetate upon photoinduced degradation of these
      nanoparticles. No significant toxicity of these nanoparticles was found at the
      concentrations up to 1000 MUg/mL before or after light irradiation. Further
      encapsulation and triggered release of a bioactive model drug (Tagalsin G) was
      evaluated for RAW 264.7 cells. Tagalsin G encapsulated in nanoparticles did not
      show cytotoxity to cells, while light triggered the release of Tagalsin G
      increasing cell death dramatically from 9% to 67%. Our model studies show a new
      promising strategy to trigger drug release in cells.

PMID- 22646924
TI  - Haploidentical bone marrow transplants for haematological malignancies using non
      myeloablative conditioning therapy and post-transplant immunosuppression with
      cyclophosphamide: results from a single Australian centre.
AB  - AIMS: To demonstrate safety and efficacy of haploidentical bone marrow
      transplantation with non-myeloablative conditioning and high-dose post-transplant
      cyclophosphamide in adult patients with leukaemia or lymphoma. BACKGROUND: Human
      leukocyte antigen haploidentical bone marrow transplantation is a treatment
      option in patients with haematological malignancies who have no available human
      leukocyte antigen-matched donor but is limited by conditioning regimen toxicity,
      graft failure, relapse and graft-versus-host disease (GvHD). METHODS: Twelve
      patients, median age of 51 years, underwent transplantation with T cell replete
      bone marrow from a haplotype-matched relative. The conditioning regimen consisted
      of cyclophosphamide, fludarabine and low-dose total body irradiation. Post
      transplant immunosuppression consisted of a single dose of cyclophosphamide 50
      mg/kg on day 3, followed by oral tacrolimus and mycophenolate mofetil. Outcomes
      reported are overall survival, engraftment and chimerism, toxicity, and clinical
      outcome. RESULTS: All patients had neutrophil recovery (median 14.5 days), and 11
      of 12 had platelet engraftment (median 17 days). Two patients had autologous
      reconstitution. Seven of nine assessable patients had complete donor chimerism.
      Four patients had grades II-III GvHD, and none had grade IV GvHD. Four patients
      developed limited stage chronic GvHD. Five patients with acute myeloid leukaemia
      relapsed. Two patients died of nonrelapse causes, both from other malignancies,
      and five patients remain alive and relapse free. Median overall survival was 324
      days (range 88-1163). CONCLUSION: This regimen is feasible and well tolerated in
      older patients with high-risk leukaemia or lymphoma, with minimal short-term
      toxicity and low rates of GvHD. The proportion of disease-free survivors
      indicates a graft-versus-malignancy effect is present in survivors.

PMID- 22646925
TI  - Essential fatty acids: food for mind and body.

PMID- 22646926
TI  - National Institute on Aging at middle age--its past, present, and future.
AB  - The National Institute on Aging (NIA) at the National Institutes of Health (NIH)
      leads the federal effort conducting and supporting research on aging. It is also
      designated as the lead within NIH for research on Alzheimer's disease. Since
      NIA's establishment in 1974, it has grown to a billion dollar enterprise
      featuring a balanced program of basic, clinical, and behavioral and social
      science. Investigator-initiated research and strategic investments have been
      critical to the NIA's success in bringing new insights and understandings to
      aging processes and diseases and conditions associated with advancing age. In
      recent years, constraints in the growth of resources have posed new challenges as
      the NIA and NIH leadership seek to maintain a robust and productive program. This
      article will review the history of the NIA, discuss current programs and
      priorities, and point to new directions in research, looking ahead.

PMID- 22646927
TI  - In vivo clearance and toxicity of monodisperse iron oxide nanocrystals.
AB  - Thermal decomposition of organometallic precursors has been found to generate
      highly crystalline iron oxide (IO) nanocrystals that display superior MR contrast
      and lower polydispersity than IO nanocrystals synthesized by aqueous
      precipitation. In the present study, the in vivo characteristics of IO
      nanocrystals prepared by the thermal decomposition route and then coated with a
      phospholipid containing a pendant poly(ethylene glycol) chain are examined. The
      size and surface chemistry of the IO nanocrystal influence the biodistibution,
      the rate of biodegradation and bioclearance, and the biodegradation products. We
      conclude that the in vivo fate of PEGylated monodisperse IO nanocrystals and the
      iron, phospholipid, and oleic acid biodegradation products may influence the
      cellular environments in the organs and blood that can determine their safety in
      the body.

PMID- 22646928
TI  - Heat shock protein-90 inhibitor, NVP-AUY922, is effective in combination with
      fludarabine against chronic lymphocytic leukemia cells cultured on CD40L-stromal
      layer and inhibits their activated/proliferative phenotype.
AB  - Chronic lymphocytic leukemia (CLL) involves disease infiltration into active
      proliferation centers within the lymph nodes and marrow. Successful treatment of
      CLL must involve targeting the leukemic cells in these supportive
      microenvironments. Our recent data suggest that inhibition of heat shock protein
      90 (Hsp90) may be an effective treatment for CLL. We sought to further these data
      to determine whether the Hsp90 inhibitor, AUY922 (Novartis), is effective against
      CLL cells in a supportive in vitro environment. AUY922 significantly attenuated
      changes in immunophenotype and signal transducer and activator of transcription 3
      (STAT3) signaling induced by CD40L-fibroblast co-culture but had no effect on the
      viability of CLL cells in this model. However, AUY922 in combination with
      fludarabine was significantly more effective at inducing apoptosis in cells in co
      culture than either drug alone, an effect that was irrespective of ATM/TP53
      dysfunction. In conclusion, our data suggest that further studies and clinical
      trials of AUY922 in combination with fludarabine may be warranted.

PMID- 22646929
TI  - The effects of trait and state anxiety on attention to emotional images: an eye
      tracking study.
AB  - Attentional biases for threatening stimuli have been implicated in the
      development of anxiety disorders. However, little is known about the relative
      influences of trait and state anxiety on attentional biases. This study examined
      the effects of trait and state anxiety on attention to emotional images. Low,
      mid, and high trait anxious participants completed two trial blocks of an eye
      tracking task. Participants viewed image pairs consisting of one emotional
      (threatening or positive) and one neutral image while their eye movements were
      recorded. Between trial blocks, participants underwent an anxiety induction.
      Primary analyses examined the effects of trait and state anxiety on the
      proportion of viewing time on emotional versus neutral images. State anxiety was
      associated with increased attention to threatening images for participants,
      regardless of trait anxiety. Furthermore, when in a state of anxiety, relative to
      a baseline condition, durations of initial gaze and average fixation were longer
      on threat versus neutral images. These findings were specific to the threatening
      images; no anxiety-related differences in attention were found with the positive
      images. The implications of these results for future research, models of anxiety
      related information processing, and clinical interventions for anxiety are
      discussed.

PMID- 22646930
TI  - Vg instruments inc.

PMID- 22646931
TI  - Ert.

PMID- 22646932
TI  - Rockwell international.

PMID- 22646933
TI  - Guidelines for GC/MS identification.

PMID- 22646934
TI  - Envied med laboratories, inc.

PMID- 22646936
TI  - Research appliance company.

PMID- 22646935
TI  - The lead debate.

PMID- 22646937
TI  - Sierra instruments, inc.

PMID- 22646938
TI  - International.

PMID- 22646939
TI  - Washington.

PMID- 22646941
TI  - Carl zeiss, inc.

PMID- 22646940
TI  - Industry.

PMID- 22646943
TI  - Taking things apart & putting things together.

PMID- 22646942
TI  - The global 2000 report to the president.

PMID- 22646944
TI  - Environmental quality standards development.

PMID- 22646946
TI  - Not just a book... A Celebration!

PMID- 22646945
TI  - Leeds & northrup.

PMID- 22646947
TI  - EPA seeks to amend Clean Water Act.

PMID- 22646948
TI  - Effects of acid precipitation.

PMID- 22646950
TI  - Products.

PMID- 22646949
TI  - Baseball shirts & chemist-tees.

PMID- 22646952
TI  - Literature.

PMID- 22646953
TI  - Monsanto research corporation.

PMID- 22646954
TI  - Bioanalytical systems inc.

PMID- 22646956
TI  - Learn the latest from the.

PMID- 22646957
TI  - Thermo Electron CORPORATION.

PMID- 22646959
TI  - ULTRA Scientific Inc.

PMID- 22646958
TI  - Federal energy systems inc.

PMID- 22646960
TI  - Chemistry T-shirts.

PMID- 22646961
TI  - Courses.

PMID- 22646962
TI  - Project SEED.

PMID- 22646963
TI  - Great plains gasification associates.

PMID- 22646964
TI  - Classified section.

PMID- 22646965
TI  - professional consulting services directory.

PMID- 22646966
TI  - Index to the advertisers in this issue.

PMID- 22646968
TI  - International.

PMID- 22646969
TI  - The effect of total spinal anesthesia on cardiac function in a large animal model
      of brain death.
AB  - Brain death (BD) causes cardiac dysfunction in organ donors, attributable to the
      catecholamine storm that occurs with raised intracerebral pressure (ICP). However
      the direct contribution of the spinal sympathetics has not been well described.
      We examined the effect of total spinal anesthesia (TSA) on cardiac function in a
      large animal model of BD. Eighteen pigs were allocated to 3 experimental groups:
      Group 1, the saline-treated control group; Group 2, TSA administered prior to BD;
      and Group 3, TSA administered 30 min after BD. Inflation of an intracerebral
      balloon-tipped catheter was used to induce BD. Ventricular function was assessed
      using a pressure-volume loop catheter and magnetic resonance imaging. Serum
      catecholamine levels were assessed with high performance liquid chromatography.
      Inflation of the intracerebral balloon-tipped catheter was associated with a
      dramatic rise in heart rate and blood pressure, along with increased
      concentrations of serum epinephrine and norepinephrine. This phenomenon was not
      observed in Group 2. In Group 1, there was a significant decline in
      contractility, whereas groups 2 and 3 saw no change. Group 2 had greater
      contractile reserve than groups 1 and 3. Our data demonstrate the central role of
      spinal sympathetics in the hemodynamic response to raised ICP. Further work is
      required to determine the utility of TSA in reversing cardiac dysfunction in BD
      donors.

PMID- 22646971
TI  - Site-specific modification of amino acids and peptides by aldehyde-alkyne-amine
      coupling under ambient aqueous conditions.
AB  - A highly efficient method for the direct, site-specific functionalization of
      amino acids and peptides, under ambient conditions, is described. In aqueous,
      nearly solvent-free conditions, copper(I) chloride catalyzed the aldehyde-alkyne
      amine (A(3)) coupling of amino acids to form dipropargylated products in moderate
      to excellent yields. The propargylamine functionality provides a convenient
      handle for further structural modifications, demonstrated by a subsequent one-pot
      deprotection and "click" reaction and a solution-phase peptide coupling.

PMID- 22646970
TI  - Epstein-Barr virus early antigen diffuse (EBV-EA/D)-directed immunoglobulin A
      antibodies in systemic lupus erythematosus patients.
AB  - OBJECTIVE: We sought to determine whether the serological response towards lytic
      cycle antigens of Epstein-Barr virus (EBV) is altered in systemic lupus
      erythematosus (SLE) patients. METHOD: We used enzyme-linked immunosorbent assay
      (ELISA) to investigate the prevalence of EBV early antigen diffuse (EBV-EA/D)
      antibodies in sera from 60 patients with SLE, 40 with scleroderma (SSc), 20 with
      primary Sjogren's syndrome (pSS), 20 with rheumatoid arthritis (RA), 20 healthy
      controls, and also subjects with various circulating autoantibodies. Samples from
      patients were obtained from clinics specialized within the diseases in Denmark
      and Sweden and samples from healthy controls were obtained from volunteers.
      RESULTS: A significant elevated titre of immunoglobulin (Ig)A, IgG, and IgM EBV
      EA/D antibodies was found in SLE patients compared to healthy controls, a finding
      not explained by immunosuppressive treatment or disease activity. The largest
      difference was observed for IgA EBV-EA/D antibodies (p = 0.0013) with a
      seropositive rate of 58% in SLE patients and 0% in healthy controls. RA and SSc
      patients and individuals seropositive for anti-Scl-70 were additionally found to
      have elevated titres of IgA EBV-EA/D antibodies (40%, p = 0.014; 60%, p = 0.015;
      and 38.5%, p = 0.045, respectively). However, the titres were generally lower
      than in SLE patients. CONCLUSION: Our findings support an association between EBV
      and SLE. The elevated titre of EBV-EA/D-directed IgA antibodies found in SLE
      patients could suggest reactivation of EBV in epithelial cells or reinfection of
      epithelial cells after reactivation in B cells, indicating lack of control of the
      latent infection.

PMID- 22646972
TI  - A cross-sectional study assessing the self-reported weight loss strategies used
      by adult Australian general practice patients.
AB  - BACKGROUND: Obesity is a significant public health concern. General practitioners
      (GPs) see a large percentage of the population and are well placed to provide
      weight management advice. There has been little examination of the types of
      weight loss strategies used in Australian general practice patients. This cross
      sectional study aimed to describe the proportion of normal weight, overweight and
      obese general practice patients who report trying to lose weight in the past 12
      months, the types of weight loss strategies and diets used as well as the
      proportion consulting their GP prior to trying to lose weight. METHODS: Adult
      patients completed a touchscreen computer survey while waiting for their
      appointment. Responses from 1335 patients in twelve Australian practices are
      reported. RESULTS: A larger proportion of obese patients had tried to lose weight
      in the past 12 months (73%) compared to those who were overweight (55%) and
      normal weight (33%). The most commonly used strategy used was changing diet and
      increasing exercise in all BMI categories. Less than 10% used strategies such as
      prescription medication, over the counter supplements and consulted a weight loss
      specialist. Low calorie and low fat diets were the most frequently reported diets
      used to lose weight in those who were normal weight, overweight and obese.
      Overall, the proportion seeking GP advice was low, with 12% of normal weight, 15%
      of overweight and 43% of obese patients consulting their GP prior to trying to
      lose weight. CONCLUSIONS: A large proportion of overweight or obese patients have
      tried to lose weight and utilized strategies such as changing diet and increasing
      exercise. Most attempts however were unassisted, with low rates of consultation
      with GPs and weight loss specialists. Ways to assist overweight and obese general
      practice patients with their weight loss attempts need to be identified.

PMID- 22646973
TI  - Prospective model-based comparison of different laryngoscopes for difficult
      intubation in infants.
AB  - BACKGROUND: Difficult intubation in infants is uncommon but may be a challenge
      for the anesthesiologist. Many optical-assisted techniques are available to ease
      endotracheal placement of tube but have not been systemically evaluated for
      pediatric practice. AIM: The study was performed to compare conventional
      pediatric Macintosh - with different optical laryngoscopes in difficult
      endotracheal intubation in infants. We hypothesized that inexperienced
      anesthetists would perform more successful with optical devices and that
      differences between the devices would be found. METHODS/MATERIALS: In this
      randomized controlled study, 30 anesthesia residents performed endotracheal
      intubation in an infant model of difficult airway presenting with airway
      obstruction and neck immobilization. Primary endpoints were intubation success
      rate and intubation time. Beyond that glottis view, dental trauma and difficulty
      of technique were evaluated and measured by a study observer. Macintosh,
      Airtraq((r)), Storz DCI((r)) -, and Gyrus Infant Bullard((r)) laryngoscopes were
      used in random order. After standardized briefing every resident had three
      attempts of at most 120 s with every device to place a 3-mm tube into the
      trachea. Glottis view and difficulty of technique were rated by the residents
      using classification of Cormack/Lehane and Visual Analogue Scale (VAS; 0 = easy
      to 10 = very difficult). RESULTS: Success rate was 41% with conventional
      Macintosh, 43% with Airtraq((r)), 62% with Storz DCI((r)), and 100% with
      Bullard((r)) laryngoscopes. Median time from passing the lips to first
      ventilation was 67 s (Storz DCI((r)) laryngoscope), 54 s (Macintosh
      laryngoscope), 45 s (Airtraq((r)) laryngoscope), and 21 s (Bullard((r))
      laryngoscope), respectively. Dental trauma did not occur with Bullard((r))
      laryngoscope and was frequent with Storz DCI((r)) laryngoscope (39%) and
      Macintosh laryngoscope (42%). Glottis view was best with Bullard((r))
      laryngoscope (Grade 1 in 100%) and worst with Macintosh laryngoscope (Grade 1 in
      2%). Difficulty of technique was rated with a VAS score of 2 (Bullard((r))
      laryngoscope), 4.5 (Storz DCI((r)) laryngoscope) and 6 (Airtraq((r)) - and
      Macintosh laryngoscopes). CONCLUSIONS: Inexperienced anesthetists have higher
      success rates and shorter intubation times with optical-assisted laryngoscopes
      compared with conventional Macintosh laryngoscope. Gyrus Infant Bullard((r))
      laryngoscope significantly undertakes best success rate and shortest intubation
      time with mildest impact to maxillary dents and easiest technique. Our findings
      support the hypothesis that optical laryngoscopes can be used successfully by
      inexperienced anesthetists in simulated difficult pediatric airway conditions.

PMID- 22646974
TI  - Attitudes toward concordance in psychiatry: a comparative, cross-sectional study
      of psychiatric patients and mental health professionals.
AB  - BACKGROUND: Concordance and Shared Decision-Making (SDM) are considered measures
      of the quality of care that improves communication, promotes patient
      participation, creates a positive relationship with the healthcare professional,
      and results in greater adherence with the treatment plan. METHODS: This study
      compares the attitudes of 225 mental health professionals (125 psychiatrists and
      100 psychiatry registrars) and 449 psychiatric outpatients towards SDM and
      concordance in medicine taking by using the "Leeds Attitude toward Concordance
      Scale" (LATCon). RESULTS: The internal consistency of the scale was good in all
      three samples (Cronbach's alpha: patients = 0.82, psychiatrists = 0.76, and
      registrars = 0.82). Patients scored significantly lower (1.96 +/- 0.48) than
      professionals (P < .001 in both cases), while no statistically significant
      differences between psychiatrists (2.32 +/- 0.32) and registrars (2.23 +/- 0.35)
      were registered; the three groups showed a positive attitude towards concordance
      in most indicators. Patients are clearly in favor of being informed and that
      their views and preferences be taken into account during the decision-making
      process, although they widely consider that the final decision must be the
      doctor's responsibility. Among mental health professionals, the broader
      experience provides a greater conviction of the importance of the patient's
      decision about treatment. CONCLUSIONS: We observed a positive attitude towards
      concordance in the field of psychotropic drugs prescription both in professionals
      and among patients, but further studies are needed to address the extent to which
      this apparently accepted model is reflected in the daily practice of mental
      health professionals.

PMID- 22646975
TI  - Effects of guided imagery with relaxation training on anxiety and quality of life
      among patients with inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory Bowel Disease (IBD) impacts quality of life (QoL).
      Psychological factors influence the course of the disease and should be targeted
      for intervention. METHODS: Our study was a prospective, randomised control trial.
      Fifty-six outpatients were randomly chosen and allocated to a treatment group or
      a waiting-list control group. Treatment group patients attended three relaxation
      training sessions and received an audio disc for home practice. Evaluations
      performed pre and post-treatment: state anxiety was assessed with the State-Trait
      Anxiety Inventory, QoL with the IBD Questionnaire. The Visual Analogue Scale
      assessed pain, depression, stress and mood. Patients completed a symptom
      monitoring diary. The control group's symptoms were monitored without study
      related treatment. RESULTS: Thirty-nine subjects completed the study and were
      included in the data analysis. Following the relaxation-training intervention,
      the treatment group's (n = 18) measured results showed a statistically
      significant improvement as compared to the control group (n = 21) (time by
      treatment interaction): anxiety levels decreased (p < 0.01), QoL and mood
      improved (p < 0.05), while levels of pain and stress decreased (p < 0.01).
      CONCLUSIONS: Findings indicate IBD patients may benefit from relaxation training
      in their holistic care. New studies as well as further investigation of the
      subject are warranted.

PMID- 22646976
TI  - Coupled cluster and density functional theory calculations of atomic hydrogen
      chemisorption on pyrene and coronene as model systems for graphene hydrogenation.
AB  - Ab initio coupled cluster and density functional theory studies of atomic
      hydrogen addition to the central region of pyrene and coronene as molecular
      models for graphene hydrogenation were performed. Fully relaxed potential energy
      curves (PECs) were computed at the spin-unrestricted B3LYP/cc-pVDZ level of
      theory for the atomic hydrogen attack of a center carbon atom (site A), the
      midpoint of a neighboring carbon bond (site B), and the center of a central
      hexagon (site C). Using the B3LYP/cc-pVDZ PEC geometries, we evaluated energies
      at the PBE density functional, as well as ab initio restricted open-shell ROMP2,
      ROCCSD, and ROCCSD(T) levels of theory, employing cc-pVDZ and cc-pVTZ basis sets,
      and performed a G2MS extrapolation to the ROCCSD(T)/cc-pVTZ level of theory. In
      agreement with earlier studies, we find that only site A attack leads to
      chemisorption. The G2MS entrance channel barrier heights, binding energies, and
      PEC profiles are found to agree well with a recent ab initio multireference wave
      function theory study (Bonfanti et al. J. Chem. Phys.2011, 135, 164701),
      indicating that single-reference open-shell methods including B3LYP are
      sufficient for the theoretical treatment of the interaction of graphene with a
      single hydrogen atom.

PMID- 22646977
TI  - The 'porin-cytochrome' model for microbe-to-mineral electron transfer.
AB  - Many species of bacteria can couple anaerobic growth to the respiratory reduction
      of insoluble minerals containing Fe(III) or Mn(III/IV). It has been suggested
      that in Shewanella species electrons cross the outer membrane to extracellular
      substrates via 'porin-cytochrome' electron transport modules. The molecular
      structure of an outer-membrane extracellular-facing deca-haem terminus for such a
      module has recently been resolved. It is debated how, once outside the cells,
      electrons are transferred from outer-membrane cytochromes to insoluble electron
      sinks. This may occur directly or by assemblies of cytochromes, perhaps
      functioning as 'nanowires', or via electron shuttles. Here we review recent work
      in this field and explore whether it allows for unification of the electron
      transport mechanisms supporting extracellular mineral respiration in Shewanella
      that may extend into other genera of Gram-negative bacteria.

PMID- 22646978
TI  - Molecular ecological network analyses.
AB  - BACKGROUND: Understanding the interaction among different species within a
      community and their responses to environmental changes is a central goal in
      ecology. However, defining the network structure in a microbial community is very
      challenging due to their extremely high diversity and as-yet uncultivated status.
      Although recent advance of metagenomic technologies, such as high throughout
      sequencing and functional gene arrays, provide revolutionary tools for analyzing
      microbial community structure, it is still difficult to examine network
      interactions in a microbial community based on high-throughput metagenomics data.
      RESULTS: Here, we describe a novel mathematical and bioinformatics framework to
      construct ecological association networks named molecular ecological networks
      (MENs) through Random Matrix Theory (RMT)-based methods. Compared to other
      network construction methods, this approach is remarkable in that the network is
      automatically defined and robust to noise, thus providing excellent solutions to
      several common issues associated with high-throughput metagenomics data. We
      applied it to determine the network structure of microbial communities subjected
      to long-term experimental warming based on pyrosequencing data of 16 S rRNA
      genes. We showed that the constructed MENs under both warming and unwarming
      conditions exhibited topological features of scale free, small world and
      modularity, which were consistent with previously described molecular ecological
      networks. Eigengene analysis indicated that the eigengenes represented the module
      profiles relatively well. In consistency with many other studies, several major
      environmental traits including temperature and soil pH were found to be important
      in determining network interactions in the microbial communities examined. To
      facilitate its application by the scientific community, all these methods and
      statistical tools have been integrated into a comprehensive Molecular Ecological
      Network Analysis Pipeline (MENAP), which is open-accessible now
      (http://ieg2.ou.edu/MENA). CONCLUSIONS: The RMT-based molecular ecological
      network analysis provides powerful tools to elucidate network interactions in
      microbial communities and their responses to environmental changes, which are
      fundamentally important for research in microbial ecology and environmental
      microbiology.

PMID- 22646979
TI  - Atrioventricular conduction disturbance?

PMID- 22646980
TI  - DNA-nanoparticle assemblies go organic: macroscopic polymeric materials with
      nanosized features.
AB  - BACKGROUND: One of the goals in the field of structural DNA nanotechnology is the
      use of DNA to build up 2- and 3-D nanostructures. The research in this field is
      motivated by the remarkable structural features of DNA as well as by its unique
      and reversible recognition properties. Nucleic acids can be used alone as the
      skeleton of a broad range of periodic nanopatterns and nanoobjects and in
      addition, DNA can serve as a linker or template to form DNA-hybrid structures
      with other materials. This approach can be used for the development of new
      detection strategies as well as nanoelectronic structures and devices. METHOD:
      Here we present a new method for the generation of unprecedented all-organic
      conjugated-polymer nanoparticle networks guided by DNA, based on a hierarchical
      self-assembly process. First, microphase separation of amphiphilic block
      copolymers induced the formation of spherical nanoobjects. As a second ordering
      concept, DNA base pairing has been employed for the controlled spatial definition
      of the conjugated-polymer particles within the bulk material. These networks
      offer the flexibility and the diversity of soft polymeric materials. Thus, simple
      chemical methodologies could be applied in order to tune the network's
      electrical, optical and mechanical properties. RESULTS AND CONCLUSIONS: One- two-
      and three-dimensional networks have been successfully formed. Common to all
      morphologies is the integrity of the micelles consisting of DNA block copolymer
      (DBC), which creates an all-organic engineered network.

PMID- 22646981
TI  - Lesbian, gay, bisexual, and transgender parents seeking health care for their
      children: a systematic review of the literature.
AB  - BACKGROUND: Few studies have examined the issues faced by lesbian, gay, bisexual,
      and transgender (LGBT)-parented families in relation to their access to and
      satisfaction with healthcare services for their children. It is thought that LGBT
      individuals have experienced negative interactions with the healthcare
      environment. AIMS: To systematically review the literature investigating the
      experience of LGBT parents seeking health care for their children. METHODS: A
      search of the following databases: Cochrane Library, CINAHL, Embase, Google
      Scholar, Medline, PsychInfo, Science Direct, Sociological Abstracts, Proquest,
      Scopus, and Web of Science was conducted. Using the PRISMA flow chart and
      processes of the United Kingdom Centre for Reviews and Dissemination, we selected
      and analysed relevant studies. FINDINGS: Four studies that met the inclusion
      criteria were identified. Studies showed that while the experience of LGBT
      parents seeking health care was largely positive, strategies need to be
      implemented to improve the quality of healthcare services for LGBT families and
      ensure that their needs are met. DISCUSSION: Although many LGBT parents have
      positive experiences of health care, some still experience discrimination and
      prejudice. IMPLICATIONS FOR PRACTICE: Specific educational interventions are
      needed to support LGBT parents seeking health care for their children.
      CONCLUSIONS: Further research is required to explore LGBT-parented families'
      experiences of healthcare services, and this should include children's
      experiences.

PMID- 22646983
TI  - Application of nitric oxide in drug discovery and development.
AB  - INTRODUCTION: It is becoming increasingly clear that many diseases are
      characterized or associated with perturbations in nitric oxide (NO)
      production/signaling. Therapeutics or strategies designed to restore normal NO
      homeostasis will likely have broad application and utility in human health. This
      highly complex and multi-step pathway for NO production and subsequent target
      activation provides many steps in the endogenous pathway that may be useful
      targets for drug development. Important therapeutic areas for NO-based therapies
      are inflammatory disorders, cardiovascular diseases, erectile dysfunction and
      metabolic disorders. AREAS COVERED: The following review will discuss the
      endogenous NO pathway, highlight the current market and indications for NO-based
      therapeutics, as well as identify pathway targets currently under drug
      development. Each step along the NO pathway will be discussed including exogenous
      sources of NO, use of precursors to promote NO production and downstream pathways
      affected by NO production with advantages and disadvantages highlighted for each.
      EXPERT OPINION: Development of NO-based therapeutics is and will continue to be a
      major focus of biotech and pharmaceutical companies. Understanding and utilizing
      dietary and nutritional strategies to restore NO homeostasis could allow for
      safer, quicker marketing of products that may be just as efficacious as drugs
      designed against specific targets.

PMID- 22646982
TI  - The preclinical discovery of amyotrophic lateral sclerosis drugs.
AB  - INTRODUCTION: Amyotrophic lateral sclerosis (ALS), also referred to as Lou
      Gehrig's disease, is characterized by the progressive loss of cells in the brain
      and spinal cord that leads to debilitation and death in 3 - 5 years. Only one
      therapeutic drug, riluzole, has been approved for ALS and this drug improves
      survival by 2 - 3 months. The need for new therapeutics that can postpone or slow
      the progression of the motor deficits and prolong survival is still a strong
      unmet medical need. AREAS COVERED: Although there are a number of drugs currently
      in clinical trials for ALS, this review provides an overview of the most
      promising biological targets and preclinical strategies that are currently being
      developed and deployed. The list of targets for ALS was compiled from a variety
      of websites including individual companies that have ALS programs and include
      those from the author's experience. EXPERT OPINION: Progress is being made in the
      identification of possible new therapeutics for ALS with recent efforts in
      understanding the genetic causes of the disease, susceptibility factors and the
      development of additional preclinical animal models. However, many challenges
      remain in the identification of new ALS therapeutics including: the use of
      relevant biomarkers, the need for an earlier diagnosis of the disease and
      additional animal models. Multiple strategies need to be tested in the clinic in
      order to determine what will be effective in patients.

PMID- 22646984
TI  - Searching for new cardiovascular drugs: towards improved systems for drug
      screening?
AB  - INTRODUCTION: The pharmaceutical industry urgently needs new ways of profiling
      the safety and efficacy of new cardiovascular (CV) drugs and more effectively
      transitioning these compounds through the stages of CV drug screening. This
      article reviews new technologies and methodological innovations and assesses
      whether these frameworks offer improved solutions to the problems facing the
      contemporary CV drug development. AREAS COVERED: The article comprises literature
      derived from a systematic search (from 2000 onwards) using the US patent office
      and ESP@CENET search engines as well as through multiple Boolean terms. The
      article focuses on patents relating to technologies and resources and categorises
      the patents according to their niche in the CV drug screening landscape. EXPERT
      OPINION: The CV drug pipeline is stalling due to the inability of many
      contemporary drug screening frameworks to discriminate between safe, efficacious
      therapy and hazardous off-target effect. Given the current limitations of drug
      screening frameworks, there is little scope for expanding the CV drug portfolio
      with newer, safer drugs with improved mechanisms of action. New screening
      modalities are urgently needed. Searches reveal that there are few examples of
      truly new technologies and systems in the patent literature. This apparent
      failure to revamp facets of the CV drug screening process can only perpetuate the
      inability of current platforms to improve the CV drug pipeline. Consequently,
      with few exceptions, there is stagnation in pre-clinical assay design that limits
      the pharmaceutical industry's ability to search for new drugs in new and more
      effective ways.

PMID- 22646985
TI  - Current possibilities and unresolved issues of drug target validation in
      Mycobacterium tuberculosis.
AB  - INTRODUCTION: Target driven drug discovery is a long and arduous task requiring a
      huge investment of time, energy and resources. Therefore, it is very important to
      select targets which provide the maximum chance of obtaining inhibitors that will
      be efficacious in animal models and finally in tuberculosis (TB) patients. AREAS
      COVERED: The article discusses the necessity for new targets in Mycobacterium
      tuberculosis (Mtb) drug discovery and how the functional redundancy of putative
      targets in Mtb adds a new dimension to the complexity of validation. The article
      also reviews survival kinetics using conditional knockout (KO) or knockdown (KD)
      strains and discusses how this has provided crucial information on target
      vulnerability. Furthermore, the article also comments on how the chemical
      validation of new targets using specific inhibitors has greatly supplemented the
      genetic validation efforts. EXPERT OPINION: Because of complexity of pathogenesis
      of TB, the putative drug targets need to be validated under multiple
      physiological conditions. Target protein depletion can mimic chemical inhibition
      and, therefore, will be a valuable tool in predicting the vulnerability of a
      target. Conditional KO or KD makes it possible to study the phenotypes of Mtb
      strains under a variety of physiological states. The phenotype of these strains
      should also be tested in animal models which mimic human TB more closely.
      Finally, inhibitors with confirmed mode of action can be important tools for
      validating Mtb drug targets.

PMID- 22646986
TI  - The discovery of new anesthetics by targeting GABA(A) receptors.
AB  - INTRODUCTION: Many of the general anesthetics, currently used in clinical
      practice, work through interactions with GABA(A) receptors. The last 2 decades
      has witnessed substantial progress in defining the molecular mechanisms by which
      general anesthetics interact with GABA(A) receptor sites. However, despite
      progress in the basic scientific understanding of the mechanism of action of
      general anesthetics, introduction of novel general anesthetic agents into
      clinical practice has proven quite challenging. AREAS COVERED: The focus of this
      review is on the potential for translating basic science advances into the design
      of new and improved anesthetics. The authors review general anesthetics in
      current practice as well as anesthetic drug candidates in development and discuss
      the potential for novel anesthetic drug development. EXPERT OPINION:
      Opportunities for the discovery of new anesthetics include: computational-based
      ligand-design, structure-based design, re-exploration of old structure-activity
      data, absorption, distribution, metabolism, excretion and toxicity predictions
      and high-throughput screening. The authors believe a lack of high-resolution
      three-dimensional structures of mammalian GABA(A) receptors remains a significant
      limiting factor in structure-based anesthetic drug design.

PMID- 22646987
TI  - Ambroxol: a multifaceted molecule with additional therapeutic potentials in
      respiratory disorders of childhood.
AB  - INTRODUCTION: Mucoactive drugs are currently used to cleanse the respiratory
      tract following disturbance of the normal mucociliary clearance due to mucous
      hyperproduction and/or modification of its physicochemical characteristics.
      However, in addition to possessing the ability to perform specific actions on
      airway secretion, these compounds have the capability to modulate the mechanisms
      involved in abnormal secretions. Indeed, over the years, in the postmarketing
      phase, a large number of studies have been published showing interesting
      pharmacological activities in addition to their secretagogue activity. AREAS
      COVERED: This article collates available data on ambroxol (2-amino-3,5-dibromo-N
      [trans-4-hydroxycyclohexyl]benzylamine), a metabolite of bromhexine, used as a
      secretagogue in the treatment of childhood airway diseases. This article goes
      beyond the mucoactive aspects of the drug covering its multiple pharmacological
      properties. EXPERT OPINION: The non-mucoactive functions exhibited by the
      compound may provide beneficial effects on airway structure and function in
      health and disease. Beyond the mucokinetic and secretagogue effects, ambroxol
      showed great antioxidant, anti-inflammatory, local anesthetic and surfactant
      synthesis stimulatory activities. Moreover, some antiviral and antibacterial
      activities were shown. These findings may better explain the clinical results
      observed in a variety of airway disorders and suggest additional therapeutic
      potential. Further studies are needed to better define the clinical relevance of
      these non-mucolytic activities.

PMID- 22646988
TI  - Comparative analysis of pharmacophore screening tools.
AB  - The pharmacophore concept is of central importance in computer-aided drug design
      (CADD) mainly because of its successful application in medicinal chemistry and,
      in particular, high-throughput virtual screening (HTVS). The simplicity of the
      pharmacophore definition enables the complexity of molecular interactions between
      ligand and receptor to be reduced to a handful set of features. With many
      pharmacophore screening softwares available, it is of the utmost interest to
      explore the behavior of these tools when applied to different biological systems.
      In this work, we present a comparative analysis of eight pharmacophore screening
      algorithms (Catalyst, Unity, LigandScout, Phase, Pharao, MOE, Pharmer, and POT)
      for their use in typical HTVS campaigns against four different biological targets
      by using default settings. The results herein presented show how the performance
      of each pharmacophore screening tool might be specifically related to factors
      such as the characteristics of the binding pocket, the use of specific
      pharmacophore features, and the use of these techniques in specific
      steps/contexts of the drug discovery pipeline. Algorithms with rmsd-based scoring
      functions are able to predict more compound poses correctly as overlay-based
      scoring functions. However, the ratio of correctly predicted compound poses
      versus incorrectly predicted poses is better for overlay-based scoring functions
      that also ensure better performances in compound library enrichments. While the
      ensemble of these observations can be used to choose the most appropriate class
      of algorithm for specific virtual screening projects, we remarked that
      pharmacophore algorithms are often equally good, and in this respect, we also
      analyzed how pharmacophore algorithms can be combined together in order to
      increase the success of hit compound identification. This study provides a
      valuable benchmark set for further developments in the field of pharmacophore
      search algorithms, e.g., by using pose predictions and compound library
      enrichment criteria.

PMID- 22646989
TI  - Cell-selective metabolic glycan labeling based on ligand-targeted liposomes.
AB  - A cell-specific metabolic glycan labeling strategy has been developed using
      azidosugars encapsulated in ligand-targeted liposomes. The ligands are designed
      to bind specific cell-surface receptors that are only expressed or up-regulated
      in target cells, which mediates the intracellular delivery of azidosugars. The
      delivered azidosugars are metabolically incorporated into cell-surface glycans,
      which are then imaged via a bioorthogonal reaction.

PMID- 22646990
TI  - Patient participation in the discussions of options in Spanish primary care
      consultations.
AB  - OBJECTIVES: To determine patients' participation in the discussion of options in
      primary care consultations. Identify the patients' wish to participate and their
      perceptions of their participation and explore the potential factors that may
      influence these. DESIGN: Cross-sectional study. Setting. Ninety-seven general
      practices. Participants. six hundred and fifty-eight patients who went to their
      doctors for unselected reasons. Measurements. All the encounters were videoed,
      patient participation in decision making (DM) was assessed with two tools. After
      the consultation, GPs completed a questionnaire about biomedical and relational
      information. Patients' preferences and perception of participation was explored
      with different type of questions. RESULTS: Encounters successfully videoed: 638.
      Of these, only 90 interviews clearly showed patient participation. In 161 other
      interviews, patient participation was considered possible. Questionnaires
      collected: 645. In 60% of the situations (390 encounters), patients wished they
      could have stated their views about the proposed option(s), but they perceived
      this did not happen. The degree of participation at the consultation did not
      relate significantly with the physician's ideas about the type of problem,
      evolution and treatment. Neither did any of the considered variables influence
      either the patients' wish to participate in the discussion of the suggested
      option or their perception of this. CONCLUSIONS: GPs ask patients for their
      opinion and promote discussion about the suggested plan in few encounters.
      Patients perceive this, including many patients that previously had declared not
      to be interested in being involved in decisions. These results revealed an
      important mismatch between what patients wish and what they perceive.

PMID- 22646991
TI  - Prevalence of child and adolescent mental disorders in Chile: a community
      epidemiological study.
AB  - BACKGROUND:  In Latin America, there is limited research on the prevalence of
      mental disorders in children and adolescents. This Chilean survey is the first
      national representative survey in the Latin American region to examine the
      prevalence of diagnostic and statistical manual-IV (DSM-IV) psychiatric disorders
      in the region in children and adolescents. METHODS:  Subjects aged 4-18 were
      selected using a stratified multistage design. The diagnostic interview schedule
      for children version IV (DISC-IV) was used to obtain 12-month DSM-IV diagnoses of
      affective, anxiety, conduct and substance use disorders, and supplemented with
      questionnaires examining family risk factors, family income, and service
      utilization. The parent or the primary caretaker was interviewed for children,
      aged 4-11, using the DISC-IV; however, adolescents, aged 12-18, were directly
      interviewed. RESULTS: A sample of 1558 children and adolescents was evaluated.
      Using the most stringent DISC-IV impairment algorithm, the prevalence rate for
      any psychiatric disorders was 22.5% (19.3% for boys and 25.8% for girls). The
      prevalence rate was higher among the children, aged 4-11, in comparison with
      adolescents, aged 12-18 (27.8% and 16.5%, respectively). Less than half of the
      subjects in need of services sought some form of assistance. Nearly a quarter of
      those using services did not present with a psychiatric diagnosis in the past
      year. Comorbidity was found in 24.8% of those with a disorder, but only 6.3% had
      three or more diagnoses. CONCLUSIONS: The prevalence of psychiatric disorders in
      Chile is high among children and adolescents. This study highlights the
      increasing need to reevaluate mental health services provided to children and
      adolescents in Latin America.

PMID- 22646993
TI  - Phase behavior, rheological property, and transmutation of vesicles in
      fluorocarbon and hydrocarbon surfactant mixtures.
AB  - We present a detailed study of a salt-free cationic/anionic (catanionic)
      surfactant system where a strongly alkaline cationic surfactant
      (tetradecyltrimethylammonium hydroxide, TTAOH) was mixed with a single-chain
      fluorocarbon acid (nonadecafluorodecanoic acid, NFDA) and a hyperbranched
      hydrocarbon acid [di-(2-ethylhexyl)phosphoric acid, DEHPA] in water. Typically
      the concentration of TTAOH is fixed while the total concentration and mixing
      molar ratio of NFDA and DEHPA is varied. In the absence of DEHPA and at a TTAOH
      concentration of 80 mmol.L(-1), an isotropic L(1) phase, an L(1)/L(alpha) two
      phase region, and a single L(alpha) phase were observed successively with
      increasing mixing molar ratio of NFDA to TTAOH (n(NFDA)/n(TTAOH)). In the NFDA
      rich region (n(NFDA)/n(TTAOH) > 1), a small amount of excess NFDA can be
      solubilized into the L(alpha) phase while a large excess of NFDA eventually leads
      to phase separation. When NFDA is replaced gradually by DEHPA, the mixed system
      of TTAOH/NFDA/DEHPA/H(2)O follows the same phase sequence as that of the
      TTAOH/NFDA/H(2)O system and the phase boundaries remain almost unchanged.
      However, the viscoelasticity of the samples in the single L(alpha) phase region
      becomes higher at the same total surfactant concentration as characterized by
      rheological measurements. Cryo-transmission electron microscopic (cryo-TEM)
      observations revealed a microstructural evolution from unilamellar vesicles to
      multilamellar ones and finally to gaint onions. The size of the vesicle and
      number of lamella can be controlled by adjusting the molar ratio of NFDA to
      DEHPA. The dynamic properties of the vesicular solutions have also been
      investigated. It is found that the yield stress and the storage modulus are time
      dependent after a static mixing process between the two different types of
      vesicle solutions, indicating the occurrence of a dynamic fusion between the two
      types of vesicles. The microenvironmental changes induced by aggregate
      transitions were probed by (19)F NMR as well as (31)P NMR measurements. Upon
      replacement of NFDA by DEHPA, the signal from the (19)F atoms adjacent to the
      hydrophilic headgroup disappears and that from the (19)F atoms on the main chain
      becomes sharper. This could be interpreted as an increase of microfluidity in the
      mixed vesicle bilayers at higher content of DEHPA, whose alkyl chains are
      expected to have a lower chain melting point. Our results provide basic knowledge
      on vesicle formation and their structural evolution in salt-free catanionic
      surfactant systems containing mixed ion pairs, which may contribute to a deeper
      understanding of the rules governing the formation and properties of surfactant
      self-assembly.

PMID- 22646992
TI  - Meta-analysis of amiodarone versus beta-blocker as a prophylactic therapy against
      atrial fibrillation following cardiac surgery.
AB  - BACKGROUND: Current guidelines recommend beta-blocker as the first-line
      preventive treatment of atrial fibrillation (AF) after cardiac surgery; if beta
      blocker therapy is contraindicated, then amiodarone is recommended. There is
      still lack of strong evidence of directly comparing the efficacy of amiodarone
      and beta-blocker in preventing postoperative AF (POAF). AIM: This meta-analysis
      was to determine whether amiodarione and beta-blocker are equally effective and
      safe, or one is superior in preventing POAF. METHODS: We searched the Medline,
      Web of Science, Cochrane Library databases and clinical trial databases for
      related articles published from January 1990 to October 2011. The primary outcome
      was development of AF after cardiac surgery. We used random-effects model when
      there was significant heterogeneity between trials and fixed-effects method when
      heterogeneity was negligible. Moreover, subgroup and sensitivity analyses were
      also performed. RESULTS: We identified totally six trials, which involved 1033
      patients. The amiodarone group did not significantly differ from the beta-blocker
      group in AF occurrence (risk ratio 0.77, 95% confidence interval 0.55 to 1.06, P
      = 0.11) or the length of hospital stay (weighted mean difference -0.05 day, 95%
      confidence interval -0.64 to 0.54, P = 0.86). Subgroup analysis stratified by
      different beta-blockers revealed that amiodarone significantly improved POAF as
      compared with propranolol. In addition, there was no difference in adverse events
      after operation. CONCLUSION: These data indicate that the occurrence of AF and
      length of hospital stay after surgery are similar in the amiodarone and beta
      blocker groups.

PMID- 22646994
TI  - Identification of differentially expressed genes and pathways for intramuscular
      fat deposition in pectoralis major tissues of fast-and slow-growing chickens.
AB  - BACKGROUND: Intramuscular fat (IMF) is one of the important factors influencing
      meat quality, however, for chickens, the molecular regulatory mechanisms
      underlying this trait have not yet been determined. In this study, a systematic
      identification of candidate genes and new pathways related to IMF deposition in
      chicken breast tissue has been made using gene expression profiles of two
      distinct breeds: Beijing-you (BJY), a slow-growing Chinese breed possessing high
      meat quality and Arbor Acres (AA), a commercial fast-growing broiler line.
      RESULTS: Agilent cDNA microarray analyses were conducted to determine gene
      expression profiles of breast muscle sampled at different developmental stages of
      BJY and AA chickens. Relative to d 1 when there is no detectable IMF, breast
      muscle at d 21, d 42, d 90 and d 120 (only for BJY) contained 1310 differentially
      expressed genes (DEGs) in BJY and 1080 DEGs in AA. Of these, 34-70 DEGs related
      to lipid metabolism or muscle development processes were examined further in each
      breed based on Gene Ontology (GO) analysis. The expression of several DEGs was
      correlated, positively or negatively, with the changing patterns of lipid content
      or breast weight across the ages sampled, indicating that those genes may play
      key roles in these developmental processes. In addition, based on KEGG pathway
      analysis of DEGs in both BJY and AA chickens, it was found that in addition to
      pathways affecting lipid metabolism (pathways for MAPK & PPAR signaling), cell
      junction-related pathways (tight junction, ECM-receptor interaction, focal
      adhesion, regulation of actin cytoskeleton), which play a prominent role in
      maintaining the integrity of tissues, could contribute to the IMF deposition.
      CONCLUSION: The results of this study identified potential candidate genes
      associated with chicken IMF deposition and imply that IMF deposition in chicken
      breast muscle is regulated and mediated not only by genes and pathways related to
      lipid metabolism and muscle development, but also by others involved in cell
      junctions. These findings establish the groundwork and provide new clues for
      deciphering the molecular mechanisms underlying IMF deposition in poultry.
      Further studies at the translational and posttranslational level are now required
      to validate the genes and pathways identified here.

PMID- 22646995
TI  - Gold-catalyzed simultaneous formation of C-C, C?O, and C-F bonds in the presence
      of Selectfluor: a synthesis of fluoroindenes from allene esters.
AB  - An approach for the synthesis of fluorinated indene derivatives has been
      developed via a gold-catalyzed three-component tandem reaction between allene
      esters, Selectfluor, and water.

PMID- 22646997
TI  - Nanosized multifunctional polyplexes for receptor-mediated siRNA delivery.
AB  - Although our understanding of RNAi and our knowledge on designing and
      synthesizing active and safe siRNAs significantly increased during the past
      decade, targeted delivery remains the major limitation in the development of
      siRNA therapeutics. On one hand, practical considerations dictate robust
      chemistry reproducibly providing precise carrier molecules. On the other hand,
      the multistep delivery process requires dynamic multifunctional carriers of
      substantial complexity. We present a monodisperse and multifunctional carrier
      system, synthesized by solid phase supported chemistry, for siRNA delivery in
      vitro and in vivo. The sequence-defined assembly includes a precise cationic
      (oligoethanamino)amide core, terminated at the ends by two cysteines for
      bioreversible polyplex stabilization, at a defined central position attached to a
      monodisperse polyethylene glycol chain coupled to a terminal folic acid as cell
      targeting ligand. Complexation with an endosomolytic influenza peptide-siRNA
      conjugate results in nanosized functional polyplexes of 6 nm hydrodynamic
      diameter. The necessity of each functional substructure of the carrier system for
      a specific and efficient gene silencing was confirmed. The nanosized polyplexes
      showed stability in vivo, receptor-specific cell targeting, and silencing of the
      EG5 gene in receptor-positive tumors. The nanosized appearance of these particles
      can be precisely controlled by the oligomer design (from 5.8 to 8.8 nm diameter).
      A complete surface charge shielding together with the high stability result in
      good tolerability in vivo and the absence of accumulation in nontargeted tissues
      such as liver, lung, or spleen. Due to their small size, siRNA polyplexes are
      efficiently cleared by the kidney.

PMID- 22647000
TI  - Not with ERT on the.

PMID- 22646996
TI  - Interleukin-37 reduces liver inflammatory injury via effects on hepatocytes and
      non-parenchymal cells.
AB  - BACKGROUND AND AIM: The purpose of the present study was to determine the effects
      of interleukin-37 (IL-37) on liver cells and on liver inflammation induced by
      hepatic ischemia/reperfusion (I/R). METHODS: Mice were subjected to I/R. Some
      mice received recombinant IL-37 (IL-37) at the time of reperfusion. Serum levels
      of alanine aminotransferase, and liver myeloperoxidase content were assessed.
      Serum and liver tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory
      protein-2 (MIP-2) and keratinocyte chemokine (KC) were also assessed. Hepatic
      reactive oxygen species (ROS) levels were assessed. For in vitro experiments,
      isolated hepatocytes and Kupffer cells were treated with IL-37 and inflammatory
      stimulants. Cytokine and chemokine production by these cells were assessed.
      Primary hepatocytes underwent induced cell injury and were treated with IL-37
      concurrently. Hepatocyte cytotoxicity and Bcl-2 expression were determined.
      Isolated neutrophils were treated with TNF-alpha and IL-37 and neutrophil
      activation and respiratory burst were assessed. RESULTS: IL-37 reduced hepatocyte
      injury and neutrophil accumulation in the liver after I/R. These effects were
      accompanied by reduced serum levels of TNF-alpha and MIP-2 and hepatic ROS
      levels. IL-37 significantly reduced MIP-2 and KC productions from
      lipopolysaccharide-stimulated hepatocytes and Kupffer cells. IL-37 significantly
      reduced cell death and increased Bcl-2 expression in hepatocytes. IL-37
      significantly suppressed TNF-alpha-induced neutrophil activation. CONCLUSIONS: IL
      37 is protective against hepatic I/R injury. These effects are related to the
      ability of IL-37 to reduce proinflammatory cytokine and chemokine production by
      hepatocytes and Kupffer cells as well as having a direct protective effect on
      hepatocytes. In addition, IL-37 contributes to reduce liver injury through
      suppression of neutrophil activity.

PMID- 22647002
TI  - The Clean Air Act review: Good show! Missed opportunity?

PMID- 22646999
TI  - Splenic marginal zone lymphoma with villous lymphocytes in patients with human
      immunodeficiency virus.

PMID- 22647004
TI  - Inhalable particulate matter.

PMID- 22647003
TI  - The lead debate continues.

PMID- 22647006
TI  - Prevention of significant deterioration.

PMID- 22647005
TI  - The lead debate: a response.

PMID- 22647007
TI  - O.I.corporation.

PMID- 22647008
TI  - Beckman.

PMID- 22647009
TI  - International.

PMID- 22647011
TI  - States.

PMID- 22647010
TI  - Washington.

PMID- 22647012
TI  - Science.

PMID- 22647013
TI  - Technology.

PMID- 22647014
TI  - Industry.

PMID- 22647015
TI  - Conflict over the EPA budget.

PMID- 22647016
TI  - Immobilization and teachability of hazardous wastes.

PMID- 22647019
TI  - Disposal of liquid hazardous waste.

PMID- 22647017
TI  - N-nitroso compounds.

PMID- 22647020
TI  - The effects of waste disposal on the coastal waters of Southern California.

PMID- 22647021
TI  - Particle sampling and measurement.

PMID- 22647022
TI  - The Annual ACS LabGuide- the Definitive Source for.

PMID- 22647023
TI  - Products.

PMID- 22647024
TI  - Literature.

PMID- 22647026
TI  - International.

PMID- 22647030
TI  - Chemical & engineering news.

PMID- 22647027
TI  - Courses.

PMID- 22647031
TI  - Index to the advertisers in this issue.

PMID- 22647032
TI  - Cyclophilin-A: a potential screening marker for vascular disease in type-2
      diabetes.
AB  - The pathophysiology of vascular disease in diabetes involves abnormalities in
      endothelial cells, vascular smooth muscle cells, and monocytes. The metabolic
      abnormalities that characterize diabetes, such as hyperglycemia, increased free
      fatty acids, and insulin resistance, each provoke molecular mechanisms that
      contribute to vascular dysfunction. Several molecules have been identified as
      risk markers, and have been studied to prevent progression of disease and long
      term complications. Markers such as C-reactive protein and monocyte
      chemoattractant protein-1 are used to assess risk for adverse cardiac events, but
      elevated levels are possible due to the presence of other risk factors as part of
      the natural physiological defense mechanism. In this review we discuss potential
      of cyclophilin-A, a secreted oxidative-stress-induced immunophilin with diverse
      functions. We present evidence for a significant role of cyclophilin-A in the
      pathogenesis of atherosclerosis in diabetes, and its potential as a marker for
      vascular disease in type-2 diabetes.

PMID- 22647033
TI  - The effect of aspirin on mean platelet volume in patients with paroxysmal atrial
      fibrillation.
AB  - Aspirin is one of the preferred therapies in the primary prevention of ischemic
      stroke in paroxysmal atrial fibrillation (PAF). Mean platelet volume (MPV) is a
      marker of platelet size and activation. Increased MPV reflects active and large
      platelets. The present observational study was designed to investigate whether
      aspirin treatment does affect MPV levels in patients with PAF. The study included
      101 patients who were detected to have PAF by 24-hour Holter monitoring and
      divided into two groups based on aspirin treatment [ASA (+) and ASA (-)]. MPV was
      measured. Patients with aortic and mitral stenosis, hyperthyroidism,
      hypothyroidism, malignancy, infection, and pregnancy were excluded from the
      study. Of the 101 patients, 50 had no antiplatelet therapy and 51 had daily
      aspirin (100 mg) intake. Mean age of the patients was 66 +/- 10 years and 35
      (68%) were male in ASA (+) group. There was no difference in median levels of MPV
      (9.9 vs. 10.2 fl, respectively; p = 0.9) between groups. Both uni- and
      multivariate logistic regression analyses did not show an association between MPV
      and ASA use. Our results indicate that MPV as a predictive marker of platelet
      size and activity is not affected by aspirin use in patients with PAF.

PMID- 22647034
TI  - Calibration and verification of instruments.

PMID- 22647035
TI  - Daily experiences and well-being: do memories of events matter?
AB  - Retrospective subjective well-being (SWB) refers to self-reported satisfaction
      and emotional experience over the past few weeks or months. Two studies
      investigated the mechanisms linking daily experiences to retrospective SWB.
      Participants reported events each day for 21 days (Study 1) or twice a week for
      two months (Study 2). The emotional intensity of each event was rated: (1) when
      it had recently occurred (proximal intensity); and (2) at the end of the event
      reporting period (distal intensity). Both sets of ratings were then aggregated
      across events and used to predict retrospective SWB at the end of the study. Path
      analyses showed that proximal intensity predicted retrospective SWB whereas
      distal intensity did not. The effect remained even after controlling for trait
      happiness and neuroticism. These results suggest that daily experiences influence
      retrospective SWB primarily through abstract representations of the past few
      weeks or months (as measured by aggregated proximal intensity ratings) rather
      than the explicit recollection of individual events during the same period (as
      measured by aggregated distal intensity ratings). Retrospective SWB, in turn,
      mediated the effect of daily experiences on global SWB (i.e., self-reported
      satisfaction and emotional experiences in general).

PMID- 22647036
TI  - Parentage-based pedigree reconstruction reveals female matrilineal clusters and
      male-biased dispersal in nongregarious Asian great apes, the Bornean orang-utans
      (Pongo pygmaeus).
AB  - Philopatry and sex-biased dispersal have a strong influence on population genetic
      structure, so the study of species dispersal patterns and evolutionary mechanisms
      shaping them are of great interest. Particularly nongregarious mammalian species
      present an underexplored field of study: despite their lower levels of sociality
      compared to group-living species, interactions among individuals do occur,
      providing opportunities for cryptic kin selection. Among the least gregarious
      primates are orang-utans (genus: Pongo), in which preferential associations among
      females have nevertheless been observed, but for which the presence of kin
      structures was so far unresolved because of the equivocal results of previous
      genetic studies. To clarify relatedness and dispersal patterns in orang-utans, we
      examined the largest longitudinal set of individuals with combined genetic,
      spatial and behavioural data. We found that males had significantly higher
      mitochondrial DNA (mtDNA) variation and more unique haplotypes, thus underscoring
      their different maternal ancestries compared to females. Moreover, pedigree
      reconstruction based on 24 highly polymorphic microsatellite markers and mtDNA
      haplotypes demonstrated the presence of three matrilineal clusters of generally
      highly related females with substantially overlapping ranges. In orang-utans and
      possibly other nongregarious species, comparing average biparental relatedness
      (r) of males and females to infer sex-biased dispersal is extremely problematic.
      This is because the opportunistic sampling regime frequently employed in
      nongregarious species, combined with overlapping space use of distinct
      matrilineal clusters, leads to a strong downward bias when mtDNA lineage
      membership is ignored. Thus, in nongregarious species, correct inferences of
      dispersal can only be achieved by combining several genetic approaches with
      detailed spatial information.

PMID- 22647037
TI  - Human microbiota. [corrected].

PMID- 22647038
TI  - The microbiome as a human organ.
AB  - The human organism is a complex structure composed of cells belonging to all
      three domains of life on Earth, Eukarya, Bacteria and Archaea, as well as their
      viruses. Bacterial cells of more than a thousand taxonomic units are condensed in
      a particular functional collective domain, the intestinal microbiome. The
      microbiome constitutes the last human organ under active research. Like other
      organs, and despite its intrinsic complexity, the microbiome is readily
      inherited, in a process probably involving 'small world' power law dynamics of
      construction in newborns. Like any other organ, the microbiome has physiology and
      pathology, and the individual (and collective?) health might be damaged when its
      collective population structure is altered. The diagnostic of microbiomic
      diseases involves metagenomic studies. The therapeutics of microbiome-induced
      pathology include microbiota transplantation, a technique increasingly available.
      Perhaps a new medical specialty, microbiomology, is being born.

PMID- 22647039
TI  - Metamobilomics--expanding our knowledge on the pool of plasmid encoded traits in
      natural environments using high-throughput sequencing.
AB  - A metamobilome is defined as a metagenome of circular genetic elements within a
      certain community. Metagenomic analyses of plasmids provide insights into the
      composition and structure of environmental plasmid communities. It is a promising
      method that will provide information about the types of plasmids that are present
      within environmental samples, and will give overviews about occurrences of
      plasmids as well as accessory genetic elements carried on these plasmids. A
      metamobilome library was constructed by combining multiple displacement
      amplification with pyrosequencing. This method provided a fast, efficient and
      unbiased strategy to investigate the communal gene pool of circular genetic
      elements (the metamobilome). We compared our wastewater metamobilome library with
      a wastewater metagenome library, against chromosomes, plasmids, phages and IS
      element databases, respectively. This showed that very few strictly chromosomal
      reads were present in our metamobilome library. Furthermore, data analysis showed
      that our library was strongly enriched for genes encoding plasmid-selfish traits,
      such as stability and conjugation, and most strikingly several hundred new
      putative plasmid replicases have been recovered.

PMID- 22647040
TI  - Spatial and temporal variability of the human microbiota.
AB  - The knowledge that our bodies are home to microbes is not new; van Leeuwenhoek
      first saw the microbes of the mouth and gut over three centuries ago. However,
      next generation sequencing technologies are enabling us to characterize our
      microbial consortia on an unprecedented scale, and are providing new insights
      into the range of variability of our microbiota and their contributions to our
      health. The microbiota far outnumber the human component of our selves, with 10
      times more cells and at least 100 times more genes. Moreover, while individuals
      share over 99.9% of their human genome sequence, there are vast differences in
      the microbiome (the collection of genes of our associated microbes). This raises
      the question of the extent to which our microbial community determines our human
      physiological responses and susceptibility to disease. In order to develop
      technologies that allow us to manipulate the microbiome to improve health we must
      first understand the factors that influence spatial and temporal variation,
      stability in response to perturbation, and conditions that induce community-wide
      changes.

PMID- 22647042
TI  - The adult intestinal core microbiota is determined by analysis depth and health
      status.
AB  - High-throughput molecular methods are currently exploited to characterize the
      complex and highly individual intestinal microbiota in health and disease.
      Definition of the human intestinal core microbiota, i.e. the number and the
      identity of bacteria that are shared among different individuals, is currently
      one of the main research questions. Here we apply a high-throughput phylogenetic
      microarray, for a comprehensive and high-resolution microbiota analysis, and a
      novel computational approach in a quantitative study of the core microbiota in
      over 100 individuals. In the approach presented we study how the criteria for the
      phylotype abundance or prevalence influence the resulting core in parallel with
      biological variables, such as the number and health status of the study subjects.
      We observed that the core size is highly conditional, mostly depending on the
      depth of the analysis and the required prevalence of the core taxa. Moreover, the
      core size is also affected by biological variables, of which the health status
      had a larger impact than the number of studied subjects. We also introduce a
      computational method that estimates the expected size of the core, given the
      varying prevalence and abundance criteria. The approach is directly applicable to
      sequencing data derived from intestinal and other host-associated microbial
      communities, and can be modified to include more informative definitions of core
      microbiota. Hence, we anticipate its utilization will facilitate the conceptual
      definition of the core microbiota and its consequent characterization so that
      future studies yield conclusive views on the intestinal core microbiota,
      eliminating the current controversy.

PMID- 22647041
TI  - Human milk oligosaccharide consumption by intestinal microbiota.
AB  - Human milk oligosaccharides (HMO) constitute the third most abundant class of
      molecules in breast milk. Since infants lack the enzymes required for milk glycan
      digestion, this group of carbohydrates passes undigested to the lower part of the
      intestinal tract, where they can be consumed by specific members of the infant
      gut microbiota. We review proposed mechanisms for the depletion and metabolism of
      HMO by two major bacterial genera within the infant intestinal microbiota,
      Bifidobacterium and Bacteroides.

PMID- 22647043
TI  - Metagenomics and development of the gut microbiota in infants.
AB  - The establishment of a balanced intestinal microbiota is essential for numerous
      aspects of human health, yet the microbial colonization of the gastrointestinal
      tract of infants is both complex and highly variable among individuals. In
      addition, the gastrointestinal tract microbiota is often exposed to antibiotics,
      and may be an important reservoir of resistant strains and of transferable
      resistance genes from early infancy. We are investigating by means of diverse
      metagenomic approaches several areas of microbiota development in infants,
      including the deployment of functional capabilities at the community level, the
      presence of antibiotic resistances and the population dynamics of the most
      abundant genera.

PMID- 22647044
TI  - Metagenomics and antibiotics.
AB  - Most of the bacterial species that form part of the biosphere have never been
      cultivated. In this situation, a comprehensive study of bacterial communities
      requires the utilization of non-culture-based methods, which have been named
      metagenomics. In this paper we review the use of different metagenomic techniques
      for understanding the effect of antibiotics on microbial communities, to
      synthesize new antimicrobial compounds and to analyse the distribution of
      antibiotic resistance genes in different ecosystems. These techniques include
      functional metagenomics, which serves to find new antibiotics or new antibiotic
      resistance genes, and descriptive metagenomics, which serves to analyse changes
      in the composition of the microbiota and to track the presence and abundance of
      already known antibiotic resistance genes in different ecosystems.

PMID- 22647045
TI  - Metagenomics and probiotics.
AB  - The development of extensive sequencing methods has allowed metagenomic studies
      on the human gut microbiome to be carried out. This has tremendously increased
      our knowledge on gut microbiota composition and activity, allowing microbiota
      aberrations related to different diseases to be identified. These aberrations
      constitute targets for the development of probiotics directed to correct them.
      Probiotics are extensively used to modulate gut microbiota. Nevertheless,
      metagenomic studies on the effects of probiotics are still very scarce. In the
      near future, the use of metagenomics promises to expand our understanding of
      probiotic action.

PMID- 22647046
TI  - Elucidating metabolic pathways and digging for genes of unknown function in
      microbial communities: the riboswitch approach.
AB  - In the current post-genomic era, only 3% of all genes have been annotated based
      on experimental evidence. Even though functions can readily be predicted for many
      genes, 25% of these are likely to be wrong. The most widely used methods for
      function prediction rely on sequence similarity, which might be misleading in
      many cases. Other methods such as genomic context or phylogenetic profiles have
      been developed to increase gene annotation accuracy; nevertheless these are only
      efficient when complete genome sequences are available. Here we propose a new
      approach based on riboswitch identification. Riboswitches are highly conserved
      regulators of gene expression located in the 5' untranslated region of certain
      genes. When transcribed they adopt three-dimensional structures that recognize
      their ligands with great affinity and specificity. This specificity is a key
      issue for our method, allowing functional assignment with great accuracy.

PMID- 22647048
TI  - Changes in the intestinal microbiota from adulthood through to old age.
AB  - The human intestinal microbiota comprises a complex community whose composition
      has been resolved in fine detail by recent culture-independent methodologies. The
      adult intestinal microbiota is stable within individuals, and individual specific
      when examined at high resolution. Infants and older persons, however, represent
      stages of life in which the microbiota is in flux. Since changes in the
      intestinal microbiota are associated with certain diseases or health issues, we
      have examined the composition and function of the intestinal microbiota in 500
      subjects over 65 years of age in Ireland. Medical, biochemical and immunological
      parameters were measured for all subjects. Faecal microbiota was measured by
      amplicon pyrosequencing. The data revealed significant inter-individual
      variation, especially in the proportions of some major bacterial phyla, and
      significant differences in the microbiota compared with younger adults. These
      data support the notion of modulating the intestinal microbiota of older people
      to promote enhanced nutrition utilization and to improve general health.

PMID- 22647047
TI  - Evolution of genetic diversity using networks: the human gut microbiome as a case
      study.
AB  - In order to study complex microbial communities and their associated mobile
      genetic elements, such as the human gut microbiome, evolutionists could explore
      their genetic diversity with shared sequence networks. In particular, the
      detection of remarkable structures in gene networks of the gut microbiome could
      serve to identify important functions within the community, and would ease
      comparison of data sets from microbiomes of various sources (human, ape, mouse
      etc.) in a single analysis.

PMID- 22647049
TI  - Metagenomics of human microbiome: beyond 16s rDNA.
AB  - The gut microbiota presents a symbiotic relationship with the human host playing
      a beneficial role in human health. Since its establishment, the bacterial
      community is subjected to the influence of many different factors that shape its
      composition within each individual. However, an important convergence is observed
      at functional level in the gut microbiota. A metatranscriptomic study of healthy
      individuals showed homogeneity in the composition of the active microbiota that
      increased further at functional level.

PMID- 22647050
TI  - Crosstalk between the gut microbiota and the endocannabinoid system: impact on
      the gut barrier function and the adipose tissue.
AB  - Obesity is associated with type 2 diabetes, insulin resistance and low grade
      inflammation. The gut microbiota is now considered as one of the most important
      environmental factors impacting on host physiology and metabolism. We have
      recently pointed out the role of this 'organ' on the onset of insulin resistance
      and the low grade inflammatory tone characterizing obesity. Among the mechanisms,
      we have introduced the novel concept of metabolic endotoxaemia as factor
      triggering low grade inflammation and associated disorders. More recently, two
      novel mechanisms involved in the development of gut permeability and adipose
      tissue plasticity have been identified. Specific attention has been paid to the
      role of the glucagon-like peptide 2 and the endocannabinoid system. This review
      briefly discusses the role of prebiotics as a key tool to modulate the gut
      microbiota, the gut barrier function, inflammation and the insulin resistance
      associated with obesity.

PMID- 22647051
TI  - Identifying a healthy oral microbiome through metagenomics.
AB  - We present the results of an exploratory study of the bacterial communities from
      the human oral cavity showing the advantages of pyrosequencing complex samples.
      Over 1.6 million reads from the metagenomes of eight dental plaque samples were
      taxonomically assigned through a binning procedure. We performed clustering
      analysis to discern if there were associations between non-caries and caries
      conditions in the community composition. Our results show a given bacterial
      consortium associated with cariogenic and non-cariogenic conditions, in agreement
      with the existence of a healthy oral microbiome and giving support to the idea of
      dental caries being a polymicrobial disease. The data are coherent with those
      previously reported in the literature by 16S rRNA amplification, thus giving the
      chance to link gene functions with taxonomy in further studies involving larger
      sample numbers.

PMID- 22647052
TI  - Tetracycline resistance genes and mobile genetic elements from the oral
      metagenome.
AB  - Tetracycline resistance genes are common in the human oral cavity. However, a
      complete understanding of tetracycline resistance and the vectors responsible for
      spread of resistance requires that we understand the contribution of organisms
      that cannot be cultivated in the laboratory. To do this, metagenomic approaches
      have been applied and this has allowed the isolation of novel tetracycline
      resistance genes and mobile genetic elements.

PMID- 22647053
TI  - Gut microbiota correlates with energy gain from dietary fibre and appears to be
      associated with acute and chronic intestinal diseases.
AB  - Improvements in high-throughput sequencing technologies have spurred a large
      number of studies aimed at obtaining a better understanding of the composition
      and the dynamics in gut microbiota and its associations with various human
      diseases, especially those in the intestinal tract. Here we briefly summarize
      results from three different such studies from our group, all of which used 454
      based high-throughput 16S rRNA sequence analysis combined with other microbiota
      profiling methods to determine faecal microbiota composition. In the first study,
      a controlled feeding trial, we establish that energy gain from the consumption of
      up to 50 g/day of a resistant maltodextrin depends on the prevalent microbiota
      composition. Over time, resistant maltodextrin supplementation increased the
      proportion of total faecal bacteria as well as potentially beneficial
      bifidobacteria. Thus, energy gain from resistant maltodextrin in an individual
      appears to vary over time and depend on the adaptation of gut microbiota. We then
      illustrate the power of molecular tools for identifying (i) distortions in early
      microbiota development in pre-term infants and the presence of potentially novel
      pathogens contributing to necrotizing enterocolitis and (ii) a specific
      microbiota signature, based on discriminant analysis of the 16S rRNA sequences,
      that correlates with the prevalence of an early risk marker associated with
      colorectal carcinogenesis, intestinal adenoma, in elderly adults.

PMID- 22647054
TI  - Metagenomic epidemiology: a public health need for the control of antimicrobial
      resistance.
AB  - The intestine is an 'environment', a shared space where the interior and the
      exterior of the organism merge. The complexity of the intestinal microbiome
      modulates such interaction, and reflects the coordinated evolution of animals and
      intestinal microbes. The intestinal microbiome is exposed to the environmental
      resistome, to intestinal organisms from other hosts and also to microbiome
      damaging agents, such as antibiotics. The result is a 'genetic-genomic
      metagenomic reactor' where resistance genes flow among different biological units
      of different hierarchical levels, such as integrons, transposons, plasmids,
      clones, species or genetic exchange communities. Metagenomics provides the
      possibility to explore the presence of antibiotic resistance genes in all these
      biological and evolutionary units, and to identify possible 'high risk
      associations'. Multi-layered metagenomic epidemiology is required to understand
      and eventually to predict and apply interventions aiming to limit antibiotic
      resistance.

PMID- 22647056
TI  - The definition of the applicability domain relevant to skin sensitization for the
      aromatic nucleophilic substitution mechanism.
AB  - This study outlines how a glutathione reactivity assay (so-called in chemico
      data) can be used to define the applicability domain for the nucleophilic
      aromatic substitution (S(N)Ar) reaction for benzenes. This reaction is one of the
      six mechanistic domains that have been shown to be important in toxicological
      endpoints in which the ability to bind covalently to a protein is a key molecular
      initiating event. This study has analysed the experimental data, allowing a clear
      and interpretable structure-activity relationship to be developed for the S(N)Ar
      domain. The applicability domain has resulted in a series of structural alerts.
      The definition of the applicability domain for the S(N)Ar reaction and the
      resulting structural alerts are likely to be beneficial in the development of
      computational tools for category formation and read-across. The study concludes
      with how this information can be used in the development of adverse outcome
      pathways.

PMID- 22647055
TI  - Protective role of 1,25(OH)2 vitamin D3 in the mucosal injury and epithelial
      barrier disruption in DSS-induced acute colitis in mice.
AB  - BACKGROUND: Intestinal hyper-permeability plays a critical role in the
      etiopathogenesis of inflammatory bowel disease (IBD) by affecting the penetration
      of pathogens, toxic compounds and macromolecules. 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3], the active form of vitamin D, has been shown to be an important
      regulator of IBD and recent epidemiology suggests that patients with IBD have an
      impaired vitamin D status. The purpose of this study is to investigate the
      possible protective effects of 1,25(OH)2D3 on mucosal injury and epithelial
      barrier disruption on dextran sulfate sodium (DSS)-induced acute colitis model.
      METHODS: We used DSS-induced acute colitis model to investigate the protective
      effects of 1,25(OH)2D3 on mucosal injury and epithelial barrier integrity.
      Severity of colitis was evaluated by disease activity index (DAI), body weight
      (BW) change, colon length, histology, myeloperoxidase (MPO) activity, and
      proinflammatory cytokine production including tumor necrosis factor-alpha (TNF
      alpha) and interferon-gamma (IFN-gamma). In vitro the protective role of
      1,25(OH)2D3 was assessed by incubating Caco-2 cells with or without DSS and
      measuring transepithelial electrical resistance (TEER) and fluorescein
      isothiocyanate dextran (FITC-D). The intestinal permeability was analyzed by FITC
      D, bacterial translocation and measurement of lipopolysaccharide (LPS).
      Ultrastructural features of the colon tissue and Caco-2 cell monolayer were
      observed by electron microscopy. Expressions of tight junction (TJ) proteins in
      the colon mucosa and Caco-2 cells were detected by immunohistochemistry,
      immunofluorescence, Western blot and real-time fluorescent quantitative PCR,
      respectively. RESULTS: DSS-induced acute colitis model was characterized by a
      reduced BW, AUC of BW, serum calcium, higher DAI, AUC of DAI, shortened colon
      length, elevated MPO activity, worsened histologic inflammation, increased
      mononuclear cell numbers in mesenteric lymph nodes (MLNs) and colonic lamina
      propria (LP), and enhanced proteins and mRNA levels of TNF-alpha and IFN-gamma.
      1,25(OH)2D3 markedly increased expressions of TJ proteins and mRNA and decreased
      the FITC-D permeability and the level of LPS. Furthermore, 1,25(OH)2D3 abrogated
      bacterial translocation to MLNs and ameliorated ultrastructural features of the
      colon epithelium by scanning electron microscopy (SEM). In vitro, 1,25(OH)2D3
      increased TEER, TJ proteins and mRNA expressions, decreased the FITC-D
      permeability, and preserved structural integrity of the TJ in Caco-2 cells.
      CONCLUSIONS: 1,25(OH)2D3 may play a protective role in mucosal barrier
      homeostasis by maintaining the integrity of junction complexes and in healing
      capacity of the colon epithelium. 1,25(OH)2D3 may represent an attractive and
      novel therapeutic agent for the adjuvant therapy of IBD.

PMID- 22647057
TI  - Detection and correction of probe-level artefacts on microarrays.
AB  - BACKGROUND: A recent large-scale analysis of Gene Expression Omnibus (GEO) data
      found frequent evidence for spatial defects in a substantial fraction of
      Affymetrix microarrays in the GEO. Nevertheless, in contrast to quality
      assessment, artefact detection is not widely used in standard gene expression
      analysis pipelines. Furthermore, although approaches have been proposed to detect
      diverse types of spatial noise on arrays, the correction of these artefacts is
      mostly left to either summarization methods or the corresponding arrays are
      completely discarded. RESULTS: We show that state-of-the-art robust summarization
      procedures are vulnerable to artefacts on arrays and cannot appropriately correct
      for these. To address this problem, we present a simple approach to detect
      artefacts with high recall and precision, which we further improve by taking into
      account the spatial layout of arrays. Finally, we propose two correction methods
      for these artefacts that either substitute values of defective probes using
      probeset information or filter corrupted probes. We show that our approach can
      identify and correct defective probe measurements appropriately and outperforms
      existing tools. CONCLUSIONS: While summarization is insufficient to correct for
      defective probes, this problem can be addressed in a straightforward way by the
      methods we present for identification and correction of defective probes. As
      these methods output CEL files with corrected probe values that serve as input to
      standard normalization and summarization procedures, they can be easily
      integrated into existing microarray analysis pipelines as an additional pre
      processing step. An R package is freely available from
      http://www.bio.ifi.lmu.de/artefact-correction.

PMID- 22647058
TI  - Evaluation of behavioral changes and subjective distress after exposure to
      coercive inpatient interventions.
AB  - BACKGROUND: There is a lack of evidence to underpin decisions on what constitutes
      the most effective and least restrictive form of coercive intervention when
      responding to violent behavior. Therefore we compared ratings of effectiveness
      and subjective distress by 125 inpatients across four types of coercive
      interventions. METHODS: Effectiveness was assessed through ratings of patient
      behavior immediately after exposure to a coercive measure and 24 h later.
      Subjective distress was examined using the Coercion Experience Scale at
      debriefing. Regression analyses were performed to compare these outcome variables
      across the four types of coercive interventions. RESULTS: Using univariate
      statistics, no significant differences in effectiveness and subjective distress
      were found between the groups, except that patients who were involuntarily
      medicated experienced significant less isolation during the measure than patients
      who underwent combined measures. However, when controlling for the effect of
      demographic and clinical characteristics, significant differences on subjective
      distress between the groups emerged: involuntary medication was experienced as
      the least distressing overall and least humiliating, caused less physical adverse
      effects and less sense of isolation. Combined coercive interventions, regardless
      of the type, caused significantly more physical adverse effects and feelings of
      isolation than individual interventions. CONCLUSIONS: In the absence of
      information on individual patient preferences, involuntary medication may be more
      justified than seclusion and mechanical restraint as a coercive intervention. Use
      of multiple interventions requires significant justification given their
      association with significant distress.

PMID- 22647060
TI  - Pacing mode and minimizing ventricular pacing.

PMID- 22647059
TI  - Malignant triton tumor of the retroperitoneum: a case report and review of the
      literature.
AB  - BACKGROUND: Malignant triton tumors are relatively rare and highly aggressive
      tumors in which malignant schwannoma cells coexist with rhabdomyoblasts. Their
      occurrence in the retroperitoneum is uncommon and has been rarely reported. CASE
      PRESENTATION: We present the case of a patient with a retroperitoneal malignant
      triton tumor. A 32-year-old male was referred with epigastric pain and an
      abdominal mass. Computed tomography revealed a huge soft tissue retroperitoneal
      mass that involved adjacent organs and vessels. Complete resection was
      undertaken. Pathological examination confirmed the presence of a malignant triton
      tumor. The patient died two and a half months after surgery, as a result of local
      recurrence. CONCLUSION: Malignant triton tumors are uncommon sarcomas that are
      associated with a high incidence of developing local recurrence and distant
      metastases. Immunohistochemical staining showing nerve sheath differentiation
      with rhabdomyoblastic cells confirms the diagnosis. Complete excision of the
      tumor is the most effective treatment strategy for these retroperitoneal tumors.

PMID- 22647061
TI  - A physical approach to specifically improve the mobility of alkane liquid drops.
AB  - Seamless control of resistance to liquid drop movement for polar (water) and
      nonpolar alkane (n-hexadecane, n-dodecane, and n-decane) probe liquids on
      substrate surfaces was successfully demonstrated using molten linear
      poly(dimethylsiloxane) (PDMS) brush films with a range of different molecular
      weights (MWs). The ease of movement of liquid drops critically depended on
      polymer chain mobility as it relates to both polymer MW and solvent swelling on
      these chemically- and topographically identical surfaces. Our brush films
      therefore displayed lower resistances to liquid drop movement with decreasing
      polymer MW and surface tension of probe liquid as measured by contact angle (CA)
      hysteresis and tilt angle measurements. Subsequently, while mobility of water
      drops was inferior and became worse at higher MWs, n-decane drops were found to
      experience little resistance to movement on these polymer brush films.
      Calculating CA hysteresis as Deltatheta(cos) = cos theta(R) - cos theta(A)
      (theta(A) and theta(R) are the advancing and receding CAs, respectively) rather
      than the standard Deltatheta = theta(A) - theta(R) was found to be advantageous
      for estimation of the actual dynamic dewetting behavior of various probe liquids
      on an inclined substrate.

PMID- 22647062
TI  - Strategies to generate biological reagents for kinase drug discovery.
AB  - INTRODUCTION: High-throughput screening (HTS) has been and is likely to remain
      one of the most widely used tools for Hit identification in the pharmaceutical,
      biotechnology and academic sectors. It has evolved into a highly integrated and
      automated process enabling the screening of millions of compounds in a timely
      manner. It is of paramount importance that appropriate biological reagents are
      utilized in an HTS campaign as their quality and physiological relevance will
      influence the likelihood of the activities of any identified Hits translating in
      vivo. AREAS COVERED: This article covers the strategies that can be used to
      efficiently design and generate biological reagents for the development of kinase
      assays and their subsequent use in HTS campaigns. The authors describe the
      variety of molecular biology and expression methodologies available to yield
      biological reagents of high quality, physiological relevance and amenable to
      kinase drug discovery. EXPERT OPINION: The techniques now available for gene
      cloning and protein expression are vast and can be overwhelming. Therefore, we
      provide guidelines for the most effective route to generate high quality,
      physiologically relevant biological reagents for kinase drug discovery. The
      methods available for the generation of biological reagents have undergone
      significant advances and some of these have been driven by the requirements of
      HTS campaigns. If the approaches described herein are implemented, it is
      anticipated they will result in the generation of suitable biological reagents
      for the development of kinase assays for HTS campaigns.

PMID- 22647063
TI  - Computational methods for the discovery of mood disorder therapies.
AB  - INTRODUCTION: Despite the significant progress, research is still needed to
      reveal details of the complex and dynamic chemical processes operating in the
      central nervous system (CNS) and their relationship to psychological effects such
      as mood disorders. The incidence of behavioral depression is widely spread
      worldwide, with an estimated 14.8 million adults diagnosed yearly in the United
      States alone. The efficacy of current antidepressants on 50 - 60% of patients,
      their slow onset of action and the prevalence of adverse side effects highlight
      the need for developing a new generation of improved antidepressants.
      Computational methods have the potential to aid in the discovery of mood
      modulators. AREAS COVERED: This review contains three main sections: historical
      evolution of marketed antidepressants, physicochemical and structural properties
      of antidepressant compounds reported in the ChEMBL database and recent efforts in
      the design and discovery of antidepressants using computational methods. The
      authors provide details of the computational methods employed, from
      chemoinformatic analyses to molecular modeling. EXPERT OPINION: While there have
      been numerous and important findings in depression research, the high cost and
      time spent on research into new therapies for brain disorders is a risky
      undertaking. Computational methodologies can be employed to speed up the
      discovery of new antidepressants and to detect new sources of chemical compounds
      with potential antidepressant activity. Compound collections containing compounds
      already approved in the pharmaceutical and food industries that cover the
      property space and complement the structural space of CNS drugs represent a
      promising starting point for the discovery of new antidepressant agents.

PMID- 22647064
TI  - Peptide and peptoid foldamers in medicinal chemistry.
AB  - INTRODUCTION: Proteins and other biologics comprise emerging therapeutic class
      with efficacies against targets for which development of small-molecule
      antagonists has been unsuccessful. The biological function of a protein is
      intimately tied to its sequence-dependent folding. A variety of unnatural
      oligomer backbones show folding behavior analogous to proteins. Often termed
      'foldamers,' these compounds have the potential to provide the benefits of
      existing protein therapeutics while overcoming some drawbacks, such as protease
      susceptibility. AREAS COVERED: This review surveys work toward the development of
      foldamer therapeutics based on beta-peptides, alpha-peptoids, beta-peptoids and
      heterogeneous backbones composed of mixtures of these monomers with natural alpha
      residues. Bioactivities targeted by foldamers are diverse but can be broadly
      divided into two categories: i) functions that require the simple separation of
      charged and hydrophobic functional groups and ii) functions that require a
      precise and complex three-dimensional display of side chains in the folded state.
      EXPERT OPINION: A long-term goal in research on foldamers is to recreate the
      entire range of structure and function manifested by natural proteins on
      unnatural backbones. Successes in the development of bioactive foldamers not only
      show their promise, but also highlight the challenges associated with the
      invention of general and reliable design strategies. While there is still a long
      way to go to a clinically used foldamer drug, significant advances in recent
      years demonstrate the potential of such scaffolds for use in the discovery of new
      therapeutics.

PMID- 22647065
TI  - The role of long-range intermolecular interactions in discovery of new drugs.
AB  - INTRODUCTION: Long-range intermolecular interactions (interactions at distances
      between 100 and 1000 A) play an important role in the interaction between drugs
      and therapeutic targets, and design techniques based on this concept could
      significantly improve and accelerate new drug discovery. Understanding these long
      range intermolecular interactions will also help further our understanding of the
      molecular mechanisms and the underlying basic biological processes. AREAS
      COVERED: This article looks at the physical bases of long-range intermolecular
      interactions in biological systems with a brief review of the literature data to
      support this concept. The article also gives some examples of techniques used in
      drug discovery that were based on the long-range intermolecular interaction
      concept. EXPERT OPINION: The electron-ion interaction potential (EIIP) and
      average quasivalence number (AQVN) concepts shed new light on the role of long
      range intermolecular interactions in biological systems. Further research of
      physicochemical mechanisms underlying long-range interactions between biological
      molecules is necessary for a better understanding of the basic biological
      processes. The addition of the computer-aided design techniques based on the
      EIIP/AQVN concept to the research and development will lead not only to a
      significant reduction in cost but also to an acceleration in the development of
      new drugs.

PMID- 22647066
TI  - Animal models for glioma drug discovery.
AB  - INTRODUCTION: High-grade gliomas are among the most deadly of all cancer types
      and are also the most common malignant primary tumors of the CNS. Large-scale
      studies that have analyzed the transcriptional and translational expression
      patterns of glioma have found that the majority of these tumors can be
      categorized based on specific genomic anomalies. Genetically engineered mouse
      models (GEMMs) that represent the molecular subgroups of the human disease harbor
      a variety of molecular alterations that have been proven to drive gliomagenesis.
      These models provide an opportunity to assess the effects of novel therapies in
      the presence of specific molecular defects. Research using GEMMs, which are
      associated with these subclasses, allow researchers to assess drug efficacy by
      subclass. AREAS COVERED: In this review, the authors discuss the histological and
      molecular characteristics of malignant gliomas, the therapies used to treat them
      and the animal models that closely recapitulate them. EXPERT OPINION: It is
      likely that GEMMs that recapitulate the molecular character of human tumors will
      provide a more accurate prediction of individuals who may be more or less likely
      to benefit from specific therapies. This knowledge can be then used to drive
      clinical trial design and this, in turn, could lead to better therapeutic
      outcomes.

PMID- 22647067
TI  - The development of label-free cellular assays for drug discovery.
AB  - INTRODUCTION: The need to improve drug research and development productivity
      continues to drive innovation in pharmacological assays. Technologies that can
      leverage the advantages of both molecular and phenotypic assays would hold great
      promise for discovery of new medicines. AREAS COVERED: This article briefly
      reviews current label-free platforms for cell-based assays and is primarily
      focused on fundamental aspects of these assays using dynamic mass redistribution
      technology as an example. The article also presents strategies for relating label
      free profiles to molecular modes of actions of drugs. EXPERT OPINION: Emerging
      evidence suggests that label-free cellular assays are phenotypic in nature, yet
      permit molecular mechanistic deconvolution. Together with unique competency in
      throughput, sensitivity and pathway coverages, label-free cellular assays allow
      users to screen drugs against endogenous receptors in native cells (including
      disease relevant primary cells) and determine the molecular modes of action of
      drug molecules. However, there are challenges for label-free in both basic
      research and drug discovery: the deconvolution of the cellular and molecular
      mechanisms for the biosensor signatures of receptor-drug interactions, new
      methodologies for data analysis and the development of new biosensor
      technologies. These challenges will need to be met for the wide adoption of these
      assays in drug discovery.

PMID- 22647068
TI  - Advances and challenges in high-throughput microscopy for live-cell subcellular
      imaging.
AB  - INTRODUCTION: Fluorescence microscopy has seen a spectacular expansion in the
      biomedical sciences due to the advent of new probes, new contrast techniques and
      the development of super-resolution that allows imaging biological structure and
      function beyond the diffraction limit. By far, most current research microscopes
      are 'low-throughput' instruments and - in this respect - do not differ much from
      their counterparts a 100 years ago. In a context of costly clinical trials and
      depleted pipelines, compound design and candidate selection could benefit from
      microscopy-based 'screening by imaging' approaches. AREAS COVERED: The article
      identifies some of the obvious and sometimes not-so-evident bottlenecks for going
      'high-throughput' with imaging-based protocols. The article focuses on recent
      (2007 - 2010) studies, with an emphasis on live-cell screening with subcellular
      resolution and takes both instrumentation and experimental design into
      consideration. Given that most screens from pharmaceutical high-throughput
      microscopy are never disclosed, this review is necessarily biased toward
      published (academic) work. EXPERT OPINION: Despite high expectations on imaging
      based drug-discovery strategies, both robotic subcellular imaging itself and data
      mining still present major challenges that will need to be overcome to make high
      throughput microscopy as versatile and as powerful as high-end research
      microscopes. Going high throughput while keeping the high information content of
      fluorescence microscopic imaging will need concerted developments of hardware,
      image analysis and segmentation software, but probably most important is the
      design of live-cell assays that generate interpretable data. Also the
      physiological and disease relevance of the biological models amenable to high
      throughput microscopies must be critically evaluated.

PMID- 22647069
TI  - Quantification of bacterial species of the vaginal microbiome in different groups
      of women, using nucleic acid amplification tests.
AB  - BACKGROUND: The vaginal microbiome plays an important role in urogenital health.
      Quantitative real time Polymerase Chain Reaction (qPCR) assays for the most
      prevalent vaginal Lactobacillus species and bacterial vaginosis species G.
      vaginalis and A. vaginae exist, but qPCR information regarding variation over
      time is still very limited. We set up qPCR assays for a selection of seven
      species and defined the temporal variation over three menstrual cycles in a
      healthy Caucasian population with a normal Nugent score. We also explored
      differences in qPCR data between these healthy women and an 'at risk' clinic
      population of Caucasian, African and Asian women with and without bacterial
      vaginosis (BV), as defined by the Nugent score. RESULTS: Temporal stability of
      the Lactobacillus species counts was high with L. crispatus counts of 108
      copies/mL and L. vaginalis counts of 106 copies/mL. We identified 2 types of
      'normal flora' and one 'BV type flora' with latent class analysis on the combined
      data of all women. The first group was particularly common in women with a normal
      Nugent score and was characterized by a high frequency of L. crispatus, L. iners,
      L. jensenii, and L. vaginalis and a correspondingly low frequency of L. gasseri
      and A. vaginae. The second group was characterized by the predominance of L.
      gasseri and L. vaginalis and was found most commonly in healthy Caucasian women.
      The third group was commonest in women with a high Nugent score but was also seen
      in a subset of African and Asian women with a low Nugent score and was
      characterized by the absence of Lactobacillus species (except for L. iners) but
      the presence of G. vaginalis and A. vaginae. CONCLUSIONS: We have shown that the
      quantification of specific bacteria by qPCR contributes to a better description
      of the non-BV vaginal microbiome, but we also demonstrated that differences in
      populations such as risk and ethnicity also have to be taken into account. We
      believe that our selection of indicator organisms represents a feasible strategy
      for the assessment of the vaginal microbiome and could be useful for monitoring
      the microbiome in safety trials of vaginal products.

PMID- 22647071
TI  - Access to C(sp3)-C(sp2) and C(sp2)-C(sp2) bond formation via sequential
      intermolecular carbopalladation of multiple carbon-carbon bonds.
AB  - A synthetic strategy of 4-benzyl-substituted 1,3-butadiene derivatives through Pd
      catalyzed three-component coupling reaction of benzyl chlorides, alkynes, and
      monosubstituted alkenes is described. This tandem coupling reaction forms a
      C(sp(3))-C(sp(2)) bond and a C(sp(2))-C(sp(2)) bond sequentially in a single-step
      operation.

PMID- 22647072
TI  - Bulk heterojuction solar cells containing 6,6-dicyanofulvenes as n-type
      additives.
AB  - P3HT/PC(61)BM bulk heterojunction solar cells containing varying amounts of
      different 6,6-dicyanofulvenes (DCFs) were fabricated and characterized.
      Photovoltaic cells containing ternary mixtures of P3HT, 0.5 equiv of PC(61)BM,
      and 0.5 equiv of 1,4-dimethyl-2,3-diphenyl-DCF (by weight) displayed average
      power conversion efficiencies of up to 4.5% under AM 1.5 irradiation, compared to
      2.9% for reference P3HT-PC(61)BM solar cells. It was found that 1,4-dimethyl-2,3
      diphenyl-6,6-dicyanofulvene could replace up to 50 wt % of PC(61)BM in 1:1 P3HT
      PC(61)BM solar cells without sacrificing device performance.

PMID- 22647070
TI  - Pharmacotherapy for parents with attention-deficit hyperactivity disorder (ADHD):
      impact on maternal ADHD and parenting.
AB  - Given the high heritability of the disorder, attention-deficit hyperactivity
      disorder (ADHD) is common among parents of children with ADHD. Parental ADHD is
      associated with maladaptive parenting, negative parent-child interaction patterns
      and a diminished response to behavioural parent training. We describe our
      previous research demonstrating that stimulant medications for mothers with ADHD
      are associated with reductions in maternal ADHD symptoms. Although limited
      beneficial effects on self-reported parenting were also found in our study, the
      impact of ADHD medications on functional outcomes related to parenting and family
      interactions may not be sufficient for many families. Many questions remain with
      regard to how best to treat multiplex ADHD families in which a parent and child
      have ADHD. In particular, future studies are needed: (1) to evaluate how best to
      sequence pharmacotherapy, psychosocial treatment for adult ADHD and behavioural
      parenting interventions; (2) to determine the best approach to maintaining
      treatment effects over the long term for both parents and children; and (3) to
      identify individual predictors of treatment response.

PMID- 22647073
TI  - High serum levels of free cortisol indicate severity of cirrhosis in
      hemodynamically stable patients.
AB  - BACKGROUND AND AIM: We investigated: (i) the association between severity of
      cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC),
      measured before and 30 min after (T(30)) the low-dose 1-ug short synacthen test
      (LD-SST); and (ii) the prognostic value of SFC and STC. METHODS: Consecutive,
      hemodynamically stable, cirrhotic patients (34 Child-Pugh class A, 29B, and 32C)
      underwent the LD-SST. Patients were followed for at least 12 months to assess non
      transplant-related mortality. RESULTS: Child-Pugh class C patients had
      significantly higher basal levels of SFC than Child-Pugh class A or B patients.
      Prevalence of suspected adrenal dysfunction ranged between 7.4% (T(0) STC < 138
      nmol/L) and 49.4% (change in STC < 250 nmol/L) according to the threshold used.
      In receiver-operator curve analysis, the area-under-the-curve values were 0.67
      for T(30) SFC (0.51-0.79), 0.81 for Child-Pugh score (0.70-0.88), and 0.79 for
      albumin level (0.63-0.88). During the follow-up period, 16 patients with high
      T(30) SFC (>= 78.9 nmol/L) (26.2%) and one patient with low T(30) SFC (< 78.9
      nmol/L) (3.4%) died (P = 0.027 for high vs low T(30) SFC, log-rank test). Albeit
      not statistically significant, the risk of death for patients with T(30) SFC >=
      78.9 nmol/L was fivefold higher than for patients with lower levels after
      adjusting for cirrhosis severity and level of albumin. CONCLUSIONS: One-year, non
      transplant-related mortality is high among patients with T(30) levels of SFC >=
      78.9 nmol/L (26.2%). These findings might result from latent inflammatory stress
      in hemodynamically stable cirrhotic patients, detected by adrenal testing.

PMID- 22647075
TI  - Simultaneous patterning of nanoparticles and polymers using an evaporation driven
      flow in a vapor permeable template.
AB  - Nanoparticles and polymers have great potential for lowering cost and increasing
      functionality of printed sensors and electronics. However, creation of practical
      devices requires that many of these materials be patterned on a single substrate,
      and many current patterning processes can only handle a single material at a
      time, necessitating alignment of serial processing steps. Higher throughput and
      lower cost can be achieved by patterning multiple materials simultaneously. To
      this end, the microfluidic molding process is adapted to pattern various
      nanoparticle and polymer inks simultaneously, in a completely additive manner,
      with three-dimensional control and high relative positional accuracy between the
      different materials. A differential template distortion observed in channels
      containing different inks is analyzed and found to result from pressure force in
      the template due to flow of a highly viscous and highly concentrated ink in small
      channels. The resulting optimization between patterning speed and dimensional
      fidelity is discussed.

PMID- 22647074
TI  - Childhood ADHD is strongly associated with a broad range of psychiatric disorders
      during adolescence: a population-based birth cohort study.
AB  - BACKGROUND: To evaluate associations between attention-deficit/hyperactivity
      disorder (ADHD) and comorbid psychiatric disorders using research-identified
      incident cases of ADHD and population-based controls. METHODS: Subjects included
      a birth cohort of all children born 1976-1982 remaining in Rochester, MN after
      age five (n = 5,718). Among them we identified 379 ADHD incident cases and 758
      age-gender matched non-ADHD controls, passively followed to age 19 years. All
      psychiatric diagnoses were identified and abstracted, but only those confirmed by
      qualified medical professionals were included in the analysis. For each
      psychiatric disorder, cumulative incidence rates for subjects with and without
      ADHD were estimated using the Kaplan-Meier method. Corresponding hazard ratios
      (HR) were estimated using Cox models adjusted for gender and mother's age and
      education at the subject's birth. The association between ADHD and the likelihood
      of having an internalizing or externalizing disorder was summarized by estimating
      odds ratios (OR). RESULTS: Attention-deficit/hyperactivity disorder was
      associated with a significantly increased risk of adjustment disorders (HR =
      3.88), conduct/oppositional defiant disorder (HR = 9.54), mood disorders (HR =
      3.67), anxiety disorders (HR = 2.94), tic disorders (HR = 6.53), eating disorders
      (HR = 5.68), personality disorders (HR = 5.80), and substance-related disorders
      (HR = 4.03). When psychiatric comorbidities were classified on the
      internalization-externalization dimension, ADHD was strongly associated with
      coexisting internalizing/externalizing (OR = 10.6), or externalizing-only (OR =
      10.0) disorders. CONCLUSION: This population-based study confirms that children
      with ADHD are at significantly increased risk for a wide range of psychiatric
      disorders. Besides treating the ADHD, clinicians should identify and provide
      appropriate treatment for psychiatric comorbidities.

PMID- 22647076
TI  - Swedish translation, adaptation and psychometric evaluation of the Context
      Assessment Index (CAI).
AB  - BACKGROUND: The strength of and relationship between the fundamental elements
      context, evidence and facilitation of the PARIHS framework are proposed to be key
      for successful implementation of evidence into healthcare practice. A better
      understanding of the presence and strength of contextual factors is assumed to
      enhance the opportunities of adequately developing an implementation strategy for
      a specific setting. A tool for assessing context-The Context Assessment Index
      (CAI)-was developed and published 2009. A Swedish version of the instrument was
      developed and evaluated among registered nurses. This work forms the focus of
      this paper. PURPOSE: The purpose of this study was to translate the CAI into
      Swedish, adapt the instrument for use in Swedish healthcare practice and assess
      its psychometric properties. METHODS: The instrument was translated and back
      translated to English. The feasibility of items and response scales were
      evaluated through think aloud interviews with clinically active nurses.
      Psychometric properties were evaluated in a sample of registered nurses (n = 373)
      working in a variety of healthcare organisations in the Stockholm area. Item and
      factor analyses and Cronbach's alpha were computed to evaluate internal structure
      and internal consistency. RESULT: Sixteen items were modified based on the think
      aloud interviews and to adapt the instrument for use in acute care. A ceiling
      effect was observed for many items and the originally identified 37 item five
      factor model was not confirmed. Item analyses showed an overlap between factors
      and indicated a one-dimensional scale. DISCUSSION: The Swedish version of the CAI
      has a wider application than the original instrument. This might have contributed
      to the differences in factor structure. Different opportunities for further
      development of the scale are discussed. CONCLUSIONS: Further evaluation of the
      psychometric properties of the CAI is required.

PMID- 22647078
TI  - Prognostic features of patients with myelodysplastic syndromes aged < 50 years:
      update of a single-institution experience.
AB  - Fewer than 10% of patients with myelodysplastic syndromes (MDS) are younger than
      50 years. A series of 91 younger patients (median age 44 years with female
      prevalence) are reported and compared with elderly patients. Frequent karyotypic
      changes were trisomy 8 (9.8%) and monosomy 7 (5%). Twenty-three patients had
      occupational exposure to potential mutagens (benzene and solvents), with a male
      predominance, higher frequency of refractory cytopenia with multilineage
      dysplasia (RCMD) (52%) and higher frequency of monosomy 7 (21.7%). At a median
      follow-up of 72 months, 22 patients (24%) evolved to acute leukemia, with higher
      frequency being observed among the exposed cohort (39% vs. 19% non-exposed).
      Unfavorable factors for overall survival were: age > 40 years, > 5% of blasts,
      trilinear bone marrow involvement and intermediate-high World Health Organization
      Prognostic Scoring System (WPSS) risk. The present results suggest that younger
      MDS could be identified as a distinct subset. For patients belonging to the
      low/intermediate-I risk group, due to a low transformation rate, aggressive
      approaches should rarely be recommended.

PMID- 22647079
TI  - Multi-objective evolutionary design of adenosine receptor ligands.
AB  - A novel multiobjective evolutionary algorithm (MOEA) for de novo design was
      developed and applied to the discovery of new adenosine receptor antagonists.
      This method consists of several iterative cycles of structure generation,
      evaluation, and selection. We applied an evolutionary algorithm (the so-called
      Molecule Commander) to generate candidate A1 adenosine receptor antagonists,
      which were evaluated against multiple criteria and objectives consisting of high
      (predicted) affinity and selectivity for the receptor, together with good ADMET
      properties. A pharmacophore model for the human A1 adenosine receptor (hA1AR) was
      created to serve as an objective function for evolution. In addition, three
      support vector machine models based on molecular fingerprints were developed for
      the other adenosine receptor subtypes (hA2A, hA2B, and hA3) and applied as
      negative objective functions, to aim for selectivity. Structures with a higher
      evolutionary fitness with respect to ADMET and pharmacophore matching scores were
      selected as input for the next generation and thus developed toward overall
      fitter ("better") compounds. We finally obtained a collection of 3946 unique
      compounds from which we derived chemical scaffolds. As a proof-of-principle, six
      of these templates were selected for actual synthesis and subsequently tested for
      activity toward all adenosine receptors subtypes. Interestingly, scaffolds 2 and
      3 displayed low micromolar affinity for many of the adenosine receptor subtypes.
      To further investigate our evolutionary design method, we performed systematic
      modifications on scaffold 3. These modifications were guided by the substitution
      patterns as observed in the set of generated compounds that contained scaffold 3.
      We found that an increased affinity with appreciable selectivity for hA1AR over
      the other adenosine receptor subtypes was achieved through substitution of the
      scaffold; compound 3a had a Ki value of 280 nM with approximately 10-fold
      selectivity with respect to hA2AR, while 3g had a 1.6 MUM affinity for hA1AR with
      negligible affinity for the hA2A, hA2B, and hA3 receptor subtypes.

PMID- 22647077
TI  - Haematogenous abdominal wall metastasis of differentiated, alpha-fetoprotein
      negative hepatocellular carcinoma after previous antiandrogen therapy within a
      site of lipoma manifestation since childhood.
AB  - BACKGROUND: Cases with subcutaneous metastasis of differentiated hepatocellular
      carcinoma to the abdominal wall without prior seeding as a consequence of local
      interventions with a negative or normal alpha-fetoprotein level in the serum are
      extremely rare. CASE REPORT: This is the first report of a case with AFP
      negative, differentiated hepatocellular carcinoma metastasis to the abdominal
      wall within a pre-existing subcutaneous lipoma since childhood after antiandrogen
      therapy with leuprorelin and buserelin acetate for prostate cancer without
      seeding. METHODS: Clinical features including histology, immunohistochemistry,
      clinical course and surgical approach are presented. RESULTS: Histological
      examination revealed a hepatocellular carcinoma with a trabecular and
      pseudoglandular growth pattern with moderately atypical hepatocytes with
      multifocal bile formation within a lipoma. The postoperative course of abdominal
      wall reconstruction with a monocryl-prolene mesh and a local flap after
      potentially curative resection was uncomplicated. DISCUSSION AND CONCLUSION: It
      may be that previous antiandrogen treatment for prostate carcinoma contributed to
      the fact that our patient developed alpha-fetoprotein-negative and androgen
      receptor-negative subcutaneous abdominal wall metastasis within a pre-existing
      lipoma since childhood.

PMID- 22647080
TI  - Two case study evaluations of an arts-based social skills intervention for
      adolescents with childhood brain disorder.
AB  - OBJECTIVE: Arts-based programmes have been shown to be useful for individuals
      with disturbances in cognitive and behavioural functioning. The current case
      studies examined the feasibility and effectiveness of a theatre skills training
      programme to facilitate social skills and participation for adolescents with
      childhood brain disorder. METHODS: A case study approach was used with two
      adolescent participants. Focus groups were conducted immediately post
      intervention, while a battery of quantitative measures were administered pre- and
      post-treatment, as well as 8 months post-treatment. RESULTS: Perceived and
      documented improvements in social skills and participation were observed from pre
      to post-intervention and at follow-up. CONCLUSION: Results support the use of an
      arts-based intervention for youth with brain injuries to facilitate social skills
      and participation. Findings also highlight the need for more sensitive measures
      of these skills for youth with childhood brain disorder, who may have impaired
      awareness of their abilities and/or impairments in memory and language
      comprehension.

PMID- 22647081
TI  - The role of platelet-rich plasma in tissue regeneration.
AB  - Platelet-rich plasma (PRP), an autologous derivative of whole blood that contains
      a supraphysiological concentration of platelets, has gained increasing attention
      in both the scientific literature and the wider media for its potential
      application in the treatment of traumatic musculoskeletal injury. The theoretical
      benefit of PRP in providing a local environment for tissue regeneration which is
      rich in growth factors and other cytokines has been supported by in vitro and
      animal studies which suggest a positive influence on the migration and
      proliferation of a number of cell types. However, the reported clinical use of
      PRP is largely confined to the last two decades and initially centred around its
      application in dental and maxillofacial surgery. More recently, developments in
      research of the regenerative effects of PRP in a range of tissue types including
      bone, cartilage, tendon and muscle, particularly in the context of traumatic
      injury, have attracted interest in fields such as orthopaedic and plastic surgery
      where effective union of sometimes poorly vascularised and damaged tissue is a
      critical determinant of successful clinical outcome. Despite the lack of high
      quality trial data, results from clinical studies have been encouraging, and PRP
      administration remains an attractive strategy given its cost-effective and
      minimally invasive nature. In this review, we summarise the current literature on
      the use of PRP and highlight areas of controversy and emerging clinical
      applications.

PMID- 22647082
TI  - Idiopathic thrombocytopenic purpura in childhood: twenty years of experience in a
      single center.
AB  - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder
      with a variable clinical course. METHODS: A retrospective analysis was carried
      out of ITP patients presenting to a pediatric hematology-oncology department
      during a period of 20 years, with a focus on treatment and outcome. RESULTS: One
      hundred and twenty-four cases were recorded (mean patient age, 8.4 years). Forty
      nine children (39.5%) had platelet counts <10,000/uL at diagnosis. No episode of
      severe bleeding was observed. Peak incidence was observed during spring and
      summer. Respiratory infections proceeded in 58% of cases. Treatment consisted of
      i.v. immunoglobulin (IVIG) in 93 children at four dosing schedules. Sixteen
      children received corticosteroids, 10 children received anti-D immunoglobulin and
      14 received no treatment. Recovery was observed in 67% of children on IVIG and in
      50% on anti-D globulin. Eight patients did not respond initially and received
      corticosteroids. Three children with refractory thrombocytopenia received anti
      CD20 (rituximab). Fourteen children (11%) had persistent/chronic disease. In 10
      of them recovery was observed in 13 months-8 years. Splenectomy was performed in
      six children with resistant/chronic disease. CONCLUSION: ITP has a benign course
      in the majority of cases. Anti-D globulin can effectively be used as an
      alternative first-line treatment. Rituximab can successfully be used in
      refractory cases, while splenectomy has currently limited indications.

PMID- 22647083
TI  - Identification and recombinant analysis of botrocetin-2, a snake venom cofactor
      for von Willebrand factor-induced platelet agglutination.
AB  - Botrocetin is a heterodimer snake venom protein that induces von Willebrand
      factor (VWF)- and platelet glycoprotein Ib (GPIb)-dependent platelet
      agglutination in vitro. We have cloned cDNAs for a botrocetin-2 from a cDNA
      library of the venom gland of Bothrops jararaca having a high similarity with
      botrocetin subunits. Recombinant botrocetin-2, expressed in 293T cells, showed
      cofactor activity comparable to natural botrocetin. In a single subunit
      expression experiment, a dimer of the beta subunit was obtained, and it showed
      reduced, but apparent, platelet agglutination activity. Ala scanning mutagenesis
      showed that substitutions at Asp62, Asp70, Arg115, or Lys117 in the beta subunit
      reduced platelet agglutination activity. The 3D homology modeling of botrocetin-2
      complexed with the VWF A1 domain and GPIbalpha indicated that Asp62, Arg115, and
      Lys117 of the beta subunit are located near Arg218 and Asp222 of GPIbalpha,
      respectively, and that Aspbeta70 is in proximity to Gln1391 of the A1 domain. Our
      results indicate that these charged amino acid residues in the beta subunit have
      a preferential role in the activity of botrocetin-2. Since it has been time
      consuming and difficult to obtain homogeneous botrocetin from natural venom,
      recombinant botrocetin-2 has potential benefits for clinical and basic
      investigations into hemostasis and thrombosis as a standard reagent.

PMID- 22647084
TI  - Spin density projection-assisted R2 magnetic resonance imaging of the liver in
      the management of body iron stores in patients receiving multiple red blood cell
      transfusions: an audit and retrospective study in South Australia.
AB  - AIM: To assess the impact of non-invasive monitoring of liver iron concentration
      (LIC) on management of body iron stores in patients receiving multiple blood
      transfusions. METHOD: A retrospective audit was conducted on clinical data from
      40 consecutive subjects with haemolytic anaemias or ineffective haematopoiesis
      who had been monitored non-invasively for LIC over a period of at least 1 year.
      LIC was measured with spin density projection-assisted proton transverse
      relaxation rate-magnetic resonance imaging. RESULTS: Nineteen clinical decisions
      were explicitly documented in the case notes as being based on LIC results.
      Decisions comprised initiation of chelation therapy, increasing chelator dose,
      decreasing chelator dose and change of mode of delivery of deferioxamine from
      subcutaneous to intravenous. The geometrical mean LIC for the cohort dropped
      significantly (P= 0.008) from 6.8 mg Fe/g dry tissue at initial measurement to
      4.8 mg Fe/g dry tissue at final measurement. The proportion of subjects with LIC
      in the range associated with greatly increased risk of cardiac disease and death
      (>15 mg Fe/g dry tissue) dropped significantly (P= 0.01) from 14 of 40 subjects
      at initial measurement to 5 of 40 subjects at final measurement. No significant
      changes in the geometrical mean of serum ferritin or the proportion of subjects
      with serum ferritin above 2500 or 1500 ug/L were observed. CONCLUSIONS: The data
      are consistent with previous observations that introduction of non-invasive
      monitoring of LIC can contribute to a decreased body iron burden through improved
      clinical decision making and improved feedback to patients and hence improved
      adherence to chelation therapy.

PMID- 22647085
TI  - Views on traditional Chinese medicine amongst Chinese population: a systematic
      review of qualitative and quantitative studies.
AB  - BACKGROUND: Health-care professionals worldwide have started to appreciate
      patients' perspectives on the use of complementary and alternative medicine (CAM)
      particularly given its popularity. However, cultural perspectives may vary and it
      may not be possible to apply research findings on the use of CAM from the west to
      the east. OBJECTIVE: This systematic review aims to synthesize usage patterns of
      traditional Chinese medicine (TCM) amongst Chinese populations in different parts
      of the world and explore potential geographical variations. SEARCH STRATEGY: Six
      international and four Chinese databases were searched, and manual searches of
      relevant monographs and government publications were carried out. INCLUSION
      CRITERIA: Quantitative, qualitative or mixed-method research that aimed to
      investigate Chinese patients' perception of, and perspectives on, TCM was
      included. DATA EXTRACTION AND SYNTHESIS: For each study included, texts under the
      headings of 'results' or 'findings' were extracted and subjected to analysis. A
      thematic synthesis approach was adopted for synthesizing qualitative and
      quantitative studies. MAIN RESULTS: Amongst the 28 studies included, twenty were
      quantitative surveys, six were qualitative studies and two were mixed-method
      studies. The overall methodological quality was mediocre. Data synthesis
      suggested that patients from all regions share a common cultural affinity to TCM
      and consider it to be an effective complement to western medicine (WM) for
      treating chronic or serious diseases. However, heterogeneous views on (i)
      disclosing TCM use to WM doctors and (ii) the potential harm of herbs emerged
      across different study locations. DISCUSSION AND CONCLUSIONS: Future research
      should explore how variation in health systems may influence patients' perception
      of CAM in different countries.

PMID- 22647086
TI  - Family functioning in the aftermath of a natural disaster.
AB  - BACKGROUND: Increased understanding of the complex determinants of adverse child
      mental health outcomes following acute stress such as natural disasters has led
      to a resurgence of interest in the role of parent psychopathology and parenting.
      The authors investigated whether family functioning in the post-disaster
      environment would be impaired relative to a non-exposed sample and potential
      correlates with family functioning such as disaster-related exposure and child
      posttraumatic mental health symptoms. METHODS: Three months after a category 5
      tropical cyclone that impacted north Queensland Australia, school-based screening
      was undertaken to case identify children who may benefit from a mental health
      intervention. Along with obtaining informed consent, parents completed a measure
      of family functioning. RESULTS: Of 145 families of children aged 8 to 12 years,
      28.3% met criteria for dysfunction on the Family Adjustment Device, double the
      frequency in a community sample. The dysfunction group was significantly more
      likely to have experienced more internalising (anxiety/depression) symptoms.
      However, in an adjusted logistic regression model this group were not more likely
      to have elevated disaster-related exposure nor did children in these families
      validate more PTSD symptoms. CONCLUSIONS: The implications of post-disaster
      discordant family functioning and possible different causal pathways for
      depressive and PTSD-related symptomatic responses to traumatic events are
      discussed.

PMID- 22647087
TI  - PyMS: a Python toolkit for processing of gas chromatography-mass spectrometry (GC
      MS) data. Application and comparative study of selected tools.
AB  - BACKGROUND: Gas chromatography-mass spectrometry (GC-MS) is a technique
      frequently used in targeted and non-targeted measurements of metabolites. Most
      existing software tools for processing of raw instrument GC-MS data tightly
      integrate data processing methods with graphical user interface facilitating
      interactive data processing. While interactive processing remains critically
      important in GC-MS applications, high-throughput studies increasingly dictate the
      need for command line tools, suitable for scripting of high-throughput,
      customized processing pipelines. RESULTS: PyMS comprises a library of functions
      for processing of instrument GC-MS data developed in Python. PyMS currently
      provides a complete set of GC-MS processing functions, including reading of
      standard data formats (ANDI- MS/NetCDF and JCAMP-DX), noise smoothing, baseline
      correction, peak detection, peak deconvolution, peak integration, and peak
      alignment by dynamic programming. A novel common ion single quantitation
      algorithm allows automated, accurate quantitation of GC-MS electron impact (EI)
      fragmentation spectra when a large number of experiments are being analyzed. PyMS
      implements parallel processing for by-row and by-column data processing tasks
      based on Message Passing Interface (MPI), allowing processing to scale on
      multiple CPUs in distributed computing environments. A set of specifically
      designed experiments was performed in-house and used to comparatively evaluate
      the performance of PyMS and three widely used software packages for GC-MS data
      processing (AMDIS, AnalyzerPro, and XCMS). CONCLUSIONS: PyMS is a novel software
      package for the processing of raw GC-MS data, particularly suitable for scripting
      of customized processing pipelines and for data processing in batch mode. PyMS
      provides limited graphical capabilities and can be used both for routine data
      processing and interactive/exploratory data analysis. In real-life GC-MS data
      processing scenarios PyMS performs as well or better than leading software
      packages. We demonstrate data processing scenarios simple to implement in PyMS,
      yet difficult to achieve with many conventional GC-MS data processing software.
      Automated sample processing and quantitation with PyMS can provide substantial
      time savings compared to more traditional interactive software systems that
      tightly integrate data processing with the graphical user interface.

PMID- 22647088
TI  - Tumour size measurement in a mouse model using high resolution MRI.
AB  - BACKGROUND: Animal models are frequently used to assess new treatment methods in
      cancer research. MRI offers a non-invasive in vivo monitoring of tumour tissue
      and thus allows longitudinal measurements of treatment effects, without the need
      for large cohorts of animals. Tumour size is an important biomarker of the
      disease development, but to our knowledge, MRI based size measurements have not
      yet been verified for small tumours (10-2-10-1 g). The aim of this study was to
      assess the accuracy of MRI based tumour size measurements of small tumours on
      mice. METHODS: 2D and 3D T2-weighted RARE images of tumour bearing mice were
      acquired in vivo using a 7 T dedicated animal MR system. For the 3D images the
      acquired image resolution was varied. The images were exported to a PC
      workstation where the tumour mass was determined assuming a density of 1 g/cm(3),
      using an in-house developed tool for segmentation and delineation. The resulting
      data were compared to the weight of the resected tumours after sacrifice of the
      animal using regression analysis. RESULTS: Strong correlations were demonstrated
      between MRI- and necropsy determined masses. In general, 3D acquisition was not a
      prerequisite for high accuracy. However, it was slightly more accurate than 2D
      when small (<0.2 g) tumours were assessed for inter- and intraobserver variation.
      In 3D images, the voxel sizes could be increased from 1603 MUm(3) to 2403 MUm(3)
      without affecting the results significantly, thus reducing acquisition time
      substantially. CONCLUSIONS: 2D MRI was sufficient for accurate tumour size
      measurement, except for small tumours (<0.2 g) where 3D acquisition was necessary
      to reduce interobserver variation. Acquisition times between 15 and 50 minutes,
      depending on tumour size, were sufficient for accurate tumour volume measurement.
      Hence, it is possible to include further MR investigations of the tumour, such as
      tissue perfusion, diffusion or metabolic composition in the same MR session.

PMID- 22647090
TI  - Vg instruments inc.

PMID- 22647091
TI  - Allis-chalmers coal gas corporation.

PMID- 22647089
TI  - Effects of caffeine on time trial performance in sedentary men.
AB  - It is not known if ergogenic effects of caffeine ingestion in athletic groups
      occur in the sedentary. To investigate this, we used a counterbalanced, double
      blind, crossover design to examine the effects of caffeine ingestion (6 mg . kg-1
      body-mass) on exercise performance, substrate utilisation and perceived exertion
      during 30 minutes of self-paced stationary cycling in sedentary men. Participants
      performed two trials, one week apart, after ingestion of either caffeine or
      placebo one hour before exercise. Participants were instructed to cycle as
      quickly as they could during each trial. External work (J . kg-1) after caffeine
      ingestion was greater than after placebo (P = 0.001, effect size [ES] = 0.3).
      Further, heart rate, oxygen uptake and energy expenditure during exercise were
      greater after caffeine ingestion (P = 0.031, ES = 0.4; P = 0.009, ES = 0.3 and P
      = 0.018, ES = 0.3; respectively), whereas ratings of perceived exertion and
      respiratory exchange ratio values did not differ between trials (P = 0.877, ES =
      0.1; P = 0.760, ES = 0.1; respectively). The ability to do more exercise after
      caffeine ingestion, without an accompanying increase in effort sensation, could
      motivate sedentary men to participate in exercise more often and so reduce
      adverse effects of inactivity on health.

PMID- 22647092
TI  - Rockwell international.

PMID- 22647093
TI  - Atmospheric chemistry.

PMID- 22647094
TI  - 1983 WHO fellowships.

PMID- 22647095
TI  - Cost of air pollution control.

PMID- 22647096
TI  - Research support.

PMID- 22647098
TI  - Foremost-McKesson Environmental Services.

PMID- 22647097
TI  - Trace analyses.

PMID- 22647099
TI  - Monsanto research corporation.

PMID- 22647100
TI  - Martek instruments, inc.

PMID- 22647101
TI  - Columbia scientific industries corporation.

PMID- 22647102
TI  - International.

PMID- 22647103
TI  - Washington.

PMID- 22647105
TI  - State.

PMID- 22647104
TI  - Science.

PMID- 22647106
TI  - Technology.

PMID- 22647107
TI  - Industry.

PMID- 22647108
TI  - Foxboro.

PMID- 22647109
TI  - Nuclear waste disposal.

PMID- 22647110
TI  - Analyses from the Pittsburgh conference.

PMID- 22647112
TI  - Sierra instruments, inc.

PMID- 22647111
TI  - American chemical society.

PMID- 22647113
TI  - A National Contingency Plan for hazardous waste.

PMID- 22647114
TI  - Integrated pest management.

PMID- 22647115
TI  - Chemical & engineering news.

PMID- 22647116
TI  - Melvin calvin: impact on betaiotaomicron-organic chemistry.

PMID- 22647118
TI  - Short-lived radionuclides in chemistry and biology.

PMID- 22647117
TI  - Chlorinated hydrocarbons: oxidation in the biosphere.

PMID- 22647119
TI  - Products.

PMID- 22647120
TI  - Literature.

PMID- 22647121
TI  - American geological institute.

PMID- 22647122
TI  - American geological institute.

PMID- 22647123
TI  - Spring 1982 ACS NEW TITLES.

PMID- 22647125
TI  - HiaC/ROYCO INSTRUMENTS DIVISION.

PMID- 22647126
TI  - Courses.

PMID- 22647127
TI  - International.

PMID- 22647128
TI  - Classified section.

PMID- 22647129
TI  - professional consulting services directory.

PMID- 22647130
TI  - Index to the advertisers in this issue.

PMID- 22647131
TI  - Integration of distributed computing into the drug discovery process.
AB  - Grid computing offers an opportunity to gain massive computing power at low
      costs. We give a short introduction into the drug discovery process and exemplify
      the use of grid computing for image processing, docking and 3D pharmacophore
      descriptor calculations. The principle of a grid and its architecture are briefly
      explained. More emphasis is laid on the issues related to a company-wide grid
      installation and embedding the grid into the research process. The future of grid
      computing in drug discovery is discussed in the expert opinion section. Most
      needed, besides reliable algorithms to predict compound properties, is embedding
      the grid seamlessly into the discovery process. User friendly access to powerful
      algorithms without any restrictions, that is, by a limited number of licenses,
      has to be the goal of grid computing in drug discovery.

PMID- 22647132
TI  - Using Drosophila models of neurodegenerative diseases for drug discovery.
AB  - INTRODUCTION: Neurodegenerative diseases such as Alzheimer's disease, Parkinson's
      disease and Huntington's disease are increasing in prevalence as our aging
      population increases in size. Despite this, currently there are no disease
      modifying drugs available for the treatment of these conditions. Drosophila
      melanogaster is a highly tractable model organism that has been successfully used
      to emulate various aspects of these diseases in vivo. These Drosophila models
      have not been fully exploited in drug discovery and design strategies. AREAS
      COVERED: This review explores how Drosophila models can be used to facilitate
      drug discovery. Specifically, we review their uses as a physiologically-relevant
      medium to high-throughput screening tool for the identification of therapeutic
      compounds and discuss how they can aid drug discovery by highlighting disease
      mechanisms that may serve as druggable targets in the future. The reader will
      appreciate how the various attributes of Drosophila make it an unsurpassed model
      organism and how Drosophila models of neurodegeneration can contribute to drug
      discovery in a variety of ways. EXPERT OPINION: Drosophila models of human
      neurodegenerative diseases can make a significant contribution to the unmet need
      of disease-modifying therapeutic intervention for the treatment of these
      increasingly common neurodegenerative conditions.

PMID- 22647133
TI  - The use of Xenopus oocytes in drug screening.
AB  - INTRODUCTION: The physiological roles of ion channels are receiving increased
      interest in both basic research and drug discovery, and a demand for
      pharmacological approaches that can characterize or screen ion channels and their
      ligands with higher throughput has emerged. Traditionally, screening of compound
      libraries at ion channel targets has been performed using assays such as binding
      assays, fluorescence-based assays and flux assays that allow high-throughput, but
      sacrifice high data quality. The use of these assays with ion channel targets can
      also be problematic, emphasizing the usefulness of automated Xenopus oocyte
      electrophysiological assays in drug screening. AREAS COVERED: This review
      summarizes the use of Xenopus oocytes in drug screening, presents the advantages
      and disadvantages of the use of Xenopus oocytes as expression system, and
      addresses the options available for automated two-electrode voltage-clamp
      recordings from Xenopus oocytes. EXPERT OPINION: Automated and manual Xenopus
      oocyte two-electrode voltage-clamp recordings are useful and important techniques
      in drug screening. Although they are not compatible with high-throughput
      experimentation, these techniques are excellent in combination or as alternatives
      to fluorescence-based assays for hit validation, screening of focused compound
      libraries and safety screening on ion channels with their high flexibility for
      the choice of molecular targets, quality of data and reproducibility.

PMID- 22647134
TI  - Discovery and development of lantibiotics; antimicrobial agents that have
      significant potential for medical application.
AB  - INTRODUCTION: Antimicrobial drug resistance is driving the need for novel
      therapeutics. Amongst the most promising antibacterial agents that are being
      investigated as replacements for current therapeutic antibiotics are
      antibacterial peptides, such as the lanthionine-containing peptide antibiotics
      (lantibiotics). AREAS COVERED: This review focuses on the current methods used
      for discovery of potentially exploitable lantibiotics for medical applications
      and discusses relevant recent innovations that will have a positive impact on the
      discovery of useful lantibiotics. EXPERT OPINION: Recent technological advances
      in a number of fields mean that increased research into the identification and
      characterisation of new lantibiotics is feasible. We need to increase our
      understanding of the various mechanisms of antibacterial action exhibited by
      lantibiotics and apply this knowledge to peptide engineering or novel practical
      applications. The advent of next-generation sequencing approaches now negate the
      need for extensive reverse genetics and employment of bioinformatics approaches
      is greatly assisting the identification of potentially useful inhibitors in the
      genomes of a range of clinically significant bacteria. These advances in genetic
      analysis and engineering will facilitate increased exploitation of lantibiotics
      in medical therapy.

PMID- 22647135
TI  - Descriptors for antimicrobial peptides.
AB  - INTRODUCTION: A frightening increase in the number of isolated multidrug
      resistant bacterial strains linked to the decline in novel antimicrobial drugs
      entering the market is a great cause for concern. Cationic antimicrobial peptides
      (AMPs) have lately been introduced as a potential new class of antimicrobial
      drugs, and computational methods utilizing molecular descriptors can
      significantly accelerate the development of new peptide drug candidates. AREAS
      COVERED: This paper gives a broad overview of peptide and amino-acid scale
      descriptors available for AMP modeling and highlights which of these are
      currently being used in quantitative structure-activity relationship (QSAR)
      studies for AMP optimization. Additionally, some key commercial computational
      tools are discussed, and both successful and less successful studies are
      referenced, illustrating some of the challenges facing AMP scientists. Through
      examples of different peptide QSAR studies, this review highlights some of the
      missing links and illuminates some of the questions that would be interesting to
      challenge in a more systematic fashion. EXPERT OPINION: Computer-aided peptide
      QSAR using molecular descriptors may provide the necessary edge to peptide drug
      discovery, enabling successful design of a new generation anti-infective drug
      molecules. However, if this wonderful scenario is to play out, computational
      chemists and peptide microbiologists would need to start playing together and not
      just side by side.

PMID- 22647136
TI  - Motexafin gadolinium: a promising radiation sensitizer in brain metastasis.
AB  - INTRODUCTION: Motexafin gadolinium is a radiation sensitizer that is in the class
      of drugs known as texaphyrins. Though this drug is currently not FDA approved in
      the management of brain tumors, several prospective studies have been done
      showing promise with this agent, which this review highlights. AREAS COVERED:
      This paper provides a clinical context by reviewing the background of
      radiosensitizers, followed by a review of the preclinical discovery of motexafin
      gadolinium and its clinical testing. We also highlight its most promising
      applications and comment on the reasons for the observed clinical outcomes.
      EXPERT OPINION: Motexafin gadolinium is a novel radiosensitizer with clearly
      documented efficacy, particularly in patients with brain metastases. If this
      agent had been tested upfront in patients diagnosed with brain metastases from
      NSCLC who had not been delayed by the administration of systemic chemotherapy, it
      may have become part of the standard of care in this setting. Continued
      investigations using this agent are under way and remain promising.

PMID- 22647137
TI  - Lasofoxifene, from the preclinical drug discovery to the treatment of
      postmenopausal osteoporosis.
AB  - INTRODUCTION: Estrogen replacement is traditionally seen as the gold standard for
      preventing osteoporotic fractures in postmenopausal women as well as for the
      management of menopausal symptoms. However, estrogen may lead to an increased
      risk of breast and, when unopposed by progestins, endometrial cancers.
      Alternative therapies include bisphosphonates and raloxifene, a selective
      estrogen receptor modulator (SERM). While the former have been associated with
      suboptimal adherence, the latter is considerably less potent than estrogen and
      its effect in the prevention of nonvertebral fractures remains uncertain. Hence,
      there is a need for additional effective medications to prevent fractures in
      postmenopausal women that provide additional benefits. AREAS COVERED: This
      article reviews lasofoxifene, a new SERM for the treatment of postmenopausal
      osteoporosis and urogenital atrophy. The medical literature is reviewed for
      articles containing the terms 'lasofoxifene' and 'SERMs'. The manuscript reviews
      the discovery strategies and preclinical development of lasofoxifene as well as
      its clinical development. EXPERT OPINION: Recent evidence suggests that the ideal
      SERM profile for one patient may be far from ideal for another. Thus, it could be
      favorable that different SERMs may be available in the future, each with a
      somewhat different profile that may be rationally applied to various patients
      with a spectrum of needs. In this context, lasofoxifene, while retaining some of
      the adverse effects of other SERMs (i.e., hot flushes and risk of venous
      thromboembolic events), may offer an improved skeletal efficacy over raloxifene,
      addressing other postmenopausal conditions, including reduction in breast cancer
      risk and treatment of vaginal atrophy.

PMID- 22647139
TI  - Clinical relevance of systematic human papillomavirus (HPV) diagnosis in oral
      squamous cell carcinoma.
AB  - Head & Neck Cancer (HNC) is one of the most common malignancies worldwide and
      among oral neoplasias about 90-92% are squamous cell carcinomas (OSCC). Alcohol
      and tobacco consumption have been recognized as the main risk factors for
      development of OSCC. However, 10 to 20% of patients suffering from OSCC have no
      history of use of these substances. Clinico-pathological evidence suggests that
      we are dealing with virally-induced cancers, and that HPV should not be a
      relevant candidate. A systematic search of HPV in OSCC has no real relevance in
      current clinical practice even although it is still relevant in organized
      research protocols. Further studies are ongoing, with the aim of identifying
      other infectious agents, including viruses, in OSCC.

PMID- 22647140
TI  - Single chirality extraction of single-wall carbon nanotubes for the encapsulation
      of organic molecules.
AB  - The hollow inner spaces of single-wall carbon nanotubes (SWCNTs) can confine
      various types of molecules. Many remarkable phenomena have been observed inside
      SWCNTs while encapsulating organic molecules (peapods). However, a mixed
      electronic structure state of the surrounding SWCNTs has impeded a detailed
      understanding of the physical/chemical properties of peapods and their device
      applications. We present a single-chirality purification method for SWCNTs that
      can encapsulate organic molecules. A single-chiral state of (11,10) SWCNTs with a
      diameter of 1.44 nm, which is large enough for molecular encapsulation, was
      obtained after a two-step purification method: metal-semiconductor sorting and
      cesium-chloride sorting. The encapsulation of C(60) to the (11,10) SWCNTs was
      also succeeded, promising a route toward single-chirality peapod devices.

PMID- 22647138
TI  - Percutaneous microwave coagulation for eradication of VX2 tumors subcutaneously
      in rabbits.
AB  - BACKGROUND: Percutaneous microwave coagulation (PMC) has been accepted as a
      promising modality in the treatment of tumors in well-vascularized tissues such
      as liver tumors and hysteromyoma. However, PMC for treatment of tumors in low
      blood-flow tissues has been seldom reported. The aim of this study was to
      determine the feasibility and safety of PMC for the treatment of tumors in low
      blood-flow tissues in a rabbit model. METHODS: Fifteen rabbits with VX2 tumors
      implanted subcutaneously underneath the right second nipple were divided into a
      PMC group (n = 9) and a control group (n = 6). PMC was performed with output
      power of 40 W for one to two minutes. The therapeutic efficacy was evaluated by
      magnetic resonance imaging (MRI), physical examinations, survival rate, and
      histology. The cosmetic outcome after PMC was also assessed. RESULTS: In the PMC
      group, tumor eradication was achieved in six rabbits (66.7%) without any evidence
      of tumor recurrence and metastasis as proven by MRI and histological
      examinations. The mean greatest and shortest tumor diameters of these six rabbits
      were 1.83 and 1.33 cm, respectively. Slight epidermal burns, which proved
      reversible, were found in seven rabbits (77.8%). The PMC group had a
      significantly longer survival than those in the control group (P = 0.0097). The
      four rabbits with coagulated tumors survived more than three months with their
      tumors becoming nonpalpable and undetectable by MRI and histological
      examinations. CONCLUSIONS: PMC is feasible and safe in the treatment of tumors in
      low blood-flow tissues in a rabbit model. Attention should be paid to avoid skin
      burns with PMC.

PMID- 22647141
TI  - Better estimates of survival for patients considering adjuvant chemotherapy after
      surgery for early non-small-cell lung cancer.
AB  - INTRODUCTION: The aim of this study was to summarise and describe survival data
      from contemporary randomised trials of platinum-based adjuvant chemotherapy for
      patients with non-small-cell lung cancer (NSCLC). The goal was to assist
      clinicians to provide better estimates of survival for patients considering
      adjuvant chemotherapy following surgical resection for NSCLC. METHODS: Randomised
      trials of cisplatin-based adjuvant chemotherapy for resected NSCLC were
      identified. Survival rates at 1, 2, 5, 7 and 10 years and the following
      percentiles (scenario): 90th (worst case), 75th (lower typical), median, 25th
      (upper typical) and 10th (best case) were extracted from each overall survival
      (OS) curve. RESULTS: Thirty-eight OS curves from 19 trials (7042 patients) were
      analysed. With adjuvant chemotherapy, the median OS rate (interquartile range) at
      1 year was 91% (85-95), 2 years was 73% (69-88), 5 years was 61% (45-65) and 7
      years was 49% (38-65). With observation only, the median OS rate (interquartile
      range) at 1 year was 88% (83-92), 2 years was 74% (65-82), 5 years was 55% (42
      58) and 7 years was 40% (34-45). In both arms, survival rates at 2, 5 and 7 years
      were well estimated by raising the 1-year survival rate to the power of two, five
      and seven respectively. Few trials reported survival rates at 10 years.
      CONCLUSION: Simple percentages and their powers provide a useful starting point
      for estimating and describing survival to patients considering adjuvant
      chemotherapy after surgery for NSCLC.

PMID- 22647142
TI  - Design and synthesis of 1,2,3-triazole-fused chiral medium-ring benzo
      heterocycles, scaffolds mimicking benzolactams.
AB  - Based on "amide-triazole bioequivalence" principle, 1,2,3-triazole-fused chiral
      medium ring benzo-heterocycles capable of mimicking benzolactams were designed.
      Their syntheses were accomplished by cycloaddition of different sugar-derived
      azidoalkynes. While triazole-fused eight-membered benzo-heterocycles were formed
      by exclusive intramolecuclar [3 + 2] cycloaddition, attempted preparation of
      seven-membered analogues led to some intermolecular cycloaddition resulting in a
      dimeric macrocyclic product, in addition to intramolecular cycloaddition
      furnishing the expected heterocycle.

PMID- 22647143
TI  - Information on pros and cons of prostate-specific antigen testing to men prior to
      blood draw: a study from the National Prostate Cancer Register (NPCR) of Sweden.
AB  - OBJECTIVE: Recent guidelines on serum testing of prostate-specific antigen (PSA)
      levels in asymptomatic men emphasize the importance of an informed decision. This
      study assessed the proportion of men who had received written or oral information
      on the possible consequences of testing of serum levels of PSA before blood draw.
      MATERIAL AND METHODS: From the National Prostate Cancer Register (NPCR) in
      Sweden, 600 men per year were randomly selected out of all men with T1c prostate
      cancer who were diagnosed in the work-up of a PSA test as a part of health
      examination in 2006-2008. In a mailed questionnaire these men were asked whether
      and how they had been informed about the pros and cons of a PSA test prior to
      blood draw. RESULTS: In total, 1621 out of 1800 men (90.1%) responded to the
      questionnaire; 39/1563 (2.5%) reported that they had received only written
      information before testing, 179/1563 (11.5%) had received both oral and written
      information, 763/1563 (48.8%) had received oral information only, 423/1563
      (27.1%) had not received any information and 159/1563 (10.2%) were not aware of
      that a PSA test had been performed. CONCLUSIONS: The proportion of men who had
      received written information on the pros and cons of a PSA test before blood draw
      in the setting of a health examination was low. Improved routines for giving
      information to the patient before a PSA test are warranted.

PMID- 22647144
TI  - Control over position, orientation, and spacing of arrays of gold nanorods using
      chemically nanopatterned surfaces and tailored particle-particle-surface
      interactions.
AB  - The synergy of self- and directed-assembly processes and lithography provides
      intriguing avenues to fabricate translationally ordered nanoparticle
      arrangements, but currently lacks the robustness necessary to deliver complex
      spatial organization. Here, we demonstrate that interparticle spacing and local
      orientation of gold nanorods (AuNR) can be tuned by controlling the Debye length
      of AuNR in solution and the dimensions of a chemical contrast pattern.
      Electrostatic and hydrophobic selectivity for AuNR to absorb to patterned regions
      of poly(2-vinylpyridine) (P2VP) and polystyrene brushes and mats was demonstrated
      for AuNR functionalized with mercaptopropane sulfonate (MS) and poly(ethylene
      glycol), respectively. For P2VP patterns of stripes with widths comparable to the
      length of the AuNR, single- and double-column arrangements of AuNR oriented
      parallel and perpendicular to the P2VP line were obtained for MS-AuNR.
      Furthermore, the spacing of the assembled AuNR was uniform along the stripe and
      related to the ionic strength of the AuNR dispersion. The different AuNR
      arrangements are consistent with predictions based on maximization of packing of
      AuNR within the confined strip.

PMID- 22647145
TI  - Quantification of clinical scores through physiological recordings in low
      responsive patients: a feasibility study.
AB  - Clinical scores represent the gold standard in characterizing the clinical
      condition of patients in vegetative or minimally conscious state. However, they
      suffer from problems of sensitivity, specificity, subjectivity and inter-rater
      reliability.In this feasibility study, objective measures including physiological
      and neurophysiological signals are used to quantify the clinical state of 13 low
      responsive patients. A linear regression method was applied in nine patients to
      obtain fixed regression coefficients for the description of the clinical state.
      The statistical model was extended and evaluated with four patients of another
      hospital. A linear mixed models approach was introduced to handle the challenges
      of data sets obtained from different locations.Using linear backward regression
      12 variables were sufficient to explain 74.4% of the variability in the change of
      the clinical scores. Variables based on event-related potentials and
      electrocardiogram account for most of the variability.These preliminary results
      are promising considering that this is the first attempt to describe the clinical
      state of low-responsive patients in such a global and quantitative way. This new
      model could complement the clinical scores based on objective measurements in
      order to increase diagnostic reliability. Nevertheless, more patients are
      necessary to prove the conclusions of a statistical model with 12 variables.

PMID- 22647146
TI  - Genetic therapeutic approaches for Duchenne muscular dystrophy.
AB  - Despite an expansive wealth of research following the discovery of the DMD gene
      25 years ago, there is still no curative treatment for Duchenne muscular
      dystrophy. However, there are currently many promising lines of research,
      including cell-based therapies and pharmacological reagents to upregulate
      dystrophin via readthrough of nonsense mutations or by upregulation of the
      dystrophin homolog utrophin. Here we review genetic-based therapeutic strategies
      aimed at the amelioration of the DMD phenotype. These include the reintroduction
      of a copy of the DMD gene into an affected tissue by means of a viral vector;
      correction of the mutated DMD transcript by antisense oligonucleotide-induced
      exon skipping to restore the open reading frame; and direct modification of the
      DMD gene at a chromosomal level through genome editing. All these approaches are
      discussed in terms of the more recent advances, and the hurdles to be overcome if
      a comprehensive and effective treatment for DMD is to be found. These hurdles
      include the need to target all musculature of the body. Therefore any potential
      treatment would need to be administered systemically. In addition, any treatment
      needs to have a long-term effect, with the possibility of readministration, while
      avoiding any potentially detrimental immune response to the vector or transgene.

PMID- 22647147
TI  - Evaluation of serum high-density lipoprotein cholesterol levels as a prognostic
      factor in gastric cancer patients.
AB  - BACKGROUND AND AIM: Although there are some reports of an adverse effect of low
      serum high-density lipoprotein cholesterol (HDL-C) levels on gastrointestinal
      cancers, the specific correlation between serum HDL-C levels and gastric cancer
      remains unknown. METHODS: Preoperative serum HDL-C levels were retrospectively
      examined in 184 patients who had undergone gastrectomy. The patients who had
      undergone gastrectomy were divided into two groups: the normal-HDL-C group and
      the low-HDL-C group. We examined the characteristics and outcomes of these two
      groups. Univariate and multivariate analyses were performed to investigate the
      association between serum HDL-C levels and gastric cancer. RESULTS: There was no
      significant difference between the groups in terms of the progression of gastric
      cancer. In the low-HDL-C group, lymphatic and vascular invasion was significantly
      increased. The prognosis of the patients in the normal-HDL-C group was
      significantly better than those in the low-HDL-C group. CONCLUSIONS: In this
      study, a positive correlation between low preoperative serum HDL-C levels and
      prognosis for gastric cancer was demonstrated. Serum HDL-C level may be a
      clinical prognostic factor for gastric cancer patients.

PMID- 22647148
TI  - Evaluation of a newly developed media-supported 4-step approach for basic life
      support training.
AB  - OBJECTIVE: The quality of external chest compressions (ECC) is of primary
      importance within basic life support (BLS). Recent guidelines delineate the so
      called 4"-step approach" for teaching practical skills within resuscitation
      training guided by a certified instructor. The objective of this study was to
      evaluate whether a "media-supported 4-step approach" for BLS training leads to
      equal practical performance compared to the standard 4-step approach. MATERIALS
      AND METHODS: After baseline testing, 220 laypersons were either trained using the
      widely accepted method for resuscitation training (4-step approach) or using a
      newly created "media-supported 4-step approach", both of equal duration. In this
      approach, steps 1 and 2 were ensured via a standardised self-produced podcast,
      which included all of the information regarding the BLS algorithm and
      resuscitation skills. Participants were tested on manikins in the same mock
      cardiac arrest single-rescuer scenario prior to intervention, after one week and
      after six months with respect to ECC-performance, and participants were surveyed
      about the approach. RESULTS: Participants (age 23 +/- 11, 69% female) reached
      comparable practical ECC performances in both groups, with no statistical
      difference. Even after six months, there was no difference detected in the
      quality of the initial assessment algorithm or delay concerning initiation of
      CPR. Overall, at least 99% of the intervention group (n = 99; mean 1.5 +/- 0.8; 6
      point Likert scale: 1 = completely agree, 6 = completely disagree) agreed that
      the video provided an adequate introduction to BLS skills. CONCLUSIONS: The
      "media-supported 4-step approach" leads to comparable practical ECC-performance
      compared to standard teaching, even with respect to retention of skills.
      Therefore, this approach could be useful in special educational settings where,
      for example, instructors' resources are sparse or large-group sessions have to be
      prepared.

PMID- 22647149
TI  - Prevalence and associations for abnormal bleeding times in patients with renal
      insufficiency.
AB  - Platelet dysfunction and associated hemorrhagic complications are often
      encountered in patients with chronic kidney disease. This study aimed to evaluate
      the prevalence and associations for abnormal bleeding time (BT) in patients with
      renal dysfunction. Hemoglobin, hematocrit, platelet, blood urea nitrogen,
      creatinine, and parathyroid hormone levels were determined in 1716 patients
      (55.18 +/- 17.19 years, men 50.8%). For these patients, BTs were estimated using
      a platelet function analyzer-100. Glomerular filtration rates (GFRs) were
      estimated using the Chronic Kidney Disease Epidemiology Collaboration equation.
      The study population was divided into six groups according to the estimated GFR
      (eGRF): group I, eGFR >= 90 ml/min/1.73 m(2); group II, 60 <= eGFR < 90
      ml/min/1.73 m(2); group III, 30 <= eGFR < 60 ml/min/1.73 m(2); group IV, 15 <=
      eGFR < 30 ml/min/1.73 m(2); group V, eGFR < 15 ml/min/1.73 m(2); and group VI,
      undergoing regular hemodialysis. Renal insufficiency was defined as eGFR < 60
      ml/min/1.73 m(2). To further investigate the role of inflammatory cytokines,
      nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) were measured in a
      327-patient subset of the total patient population (52.82 +/- 18.3 years, men
      60.9%). Abnormal BT occurred in 11.8% of group I, 15.3% of group II, 29.1% of
      group III, 37.5% of group IV, 35.0% of group V, and 32.1% of group VI. By Pearson
      correlation coefficient, eGFR (r = -0.089), hemoglobin (r = -0.127), platelet (r
      = -0.054) were correlated with BT. Multivariate analysis revealed that age [odds
      ratio (OR), 1.013; 95% CI, 1.004-1.022], renal insufficiency (eGFR < 60
      ml/min/1.73 m(2); OR, 2.271; 95% CI, 1.672-3.083), anemia (hemoglobin < 120 g/l;
      OR, 1.486; 95% CI, 1.089-2.027), and thrombocytopenia (platelet < 150 * 10(9)/l;
      OR, 1.445; 95% CI, 1.089-1.918) were independently associated with prolonged BT.
      Plasma levels of NO and TNF-alpha were increased in patients with renal
      insufficiency (eGFR < 60 ml/min/1.73 m(2)). Plasma levels of NO in renal
      insufficiency group were higher in prolonged BT than those in normal BT. A
      significant positive correlation was noted between BTs and NO levels (r = 0.152,
      p = 0.009) but not with TNF-alpha levels. The prevalence of abnormal BTs was
      higher as eGFR declined. Old age, renal insufficiency, anemia, and
      thrombocytopenia were independent associations for abnormal BT.

PMID- 22647153
TI  - Wiley-interscience.

PMID- 22647150
TI  - Proteomic profiling of Rhizobium tropici PRF 81: identification of conserved and
      specific responses to heat stress.
AB  - BACKGROUND: Rhizobium tropici strain PRF 81 (= SEMIA 4080) has been used in
      commercial inoculants for application to common-bean crops in Brazil since 1998,
      due to its high efficiency in fixing nitrogen, competitiveness against indigenous
      rhizobial populations and capacity to adapt to stressful tropical conditions,
      representing a key alternative to application of N-fertilizers. The objective of
      our study was to obtain an overview of adaptive responses to heat stress of
      strain PRF 81, by analyzing differentially expressed proteins when the bacterium
      is grown at 28 degrees C and 35 degrees C. RESULTS: Two-dimensional gel
      electrophoresis (2DE) revealed up-regulation of fifty-nine spots that were
      identified by MALDI-TOF/TOF-TOF. Differentially expressed proteins were
      associated with the functional COG categories of metabolism, cellular processes
      and signaling, information storage and processing. Among the up-regulated
      proteins, we found some related to conserved heat responses, such as molecular
      chaperones DnaK and GroEL, and other related proteins, such as translation
      factors EF-Tu, EF-G, EF-Ts and IF2. Interestingly, several oxidative stress
      responsive proteins were also up-regulated, and these results reveal the
      diversity of adaptation mechanisms presented by this thermotolerant strain,
      suggesting a cross-talk between heat and oxidative stresses. CONCLUSIONS: Our
      data provide valuable protein-expression information relevant to the ongoing
      genome sequencing of strain PRF 81, and contributes to our still-poor knowledge
      of the molecular determinants of the thermotolerance exhibited by R. tropici
      species.

PMID- 22647151
TI  - Liver analysis using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid
      enhanced magnetic resonance imaging: Correlation with histological grading and
      quantitative liver evaluation prior to hepatectomy.
AB  - AIM:   To examine the effectiveness of gadolinium-ethoxybenzyl-diethylenetriamine
      pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in the
      assessment of parenchymal liver fibrosis and quantitative liver function prior to
      hepatectomy. METHODS:   Between July 2008 and September 2011, the data of 93
      consecutive patients undergoing preoperative Gd-EOB-DTPA-enhanced MRI were
      analyzed, including serum fibrosis marker levels (hyaluronic acid, type IV
      collagen), 15-min retention rates of indocyanine green (ICG-R15) in the ICG
      clearance test, and technetium-99m galactosyl serum albumin scintigraphy results.
      Liver intensity values were obtained by calculating the differences between the
      intensity of the liver and that of other organs in the hepatobiliary phase.
      Degrees of liver fibrosis were quantitatively assessed (F0-4). MRI data were
      correlated with the prospectively acquired clinical data. RESULTS:   Varying
      degrees of liver fibrosis were detected in 31 of the 93 patients. The intensity
      ratio of the liver to spinal cord on MRI negatively correlated with hepatic
      fibrosis (R = -0.479, P < 0.001) and ICG-R15 (R = -0.492, P < 0.001). When
      patients with F0-2 (normal/moderate) and F3-4 (severe) liver fibrosis were
      compared, the intensity ratio of the enhanced liver to spinal cord (IRLS) on MRI
      was significantly lower in the F3-4 group than in the F0-2 group. IRLS was
      correlated with liver fibrosis, and, when an IRLS criterion of less than 1.702
      was used, severe liver fibrosis could be predicted with 68.8% sensitivity and
      93.5% specificity. CONCLUSION:   Preoperative Gd-EOB-DTPA-enhanced MRI analysis
      can detect quantitative indicators of liver fibrosis and function, thus aiding
      the assessment of hepatic remnants prior to hepatectomy.

PMID- 22647154
TI  - Kurz.

PMID- 22647156
TI  - Rockwell international.

PMID- 22647158
TI  - Trace analyses.

PMID- 22647157
TI  - Design for sustainability and survivability.

PMID- 22647159
TI  - Airborne dusts.

PMID- 22647160
TI  - Research support.

PMID- 22647161
TI  - The global future.

PMID- 22647162
TI  - Editorial excellence.

PMID- 22647163
TI  - Washington.

PMID- 22647164
TI  - International.

PMID- 22647165
TI  - States.

PMID- 22647166
TI  - Science.

PMID- 22647168
TI  - Industry.

PMID- 22647167
TI  - Technology.

PMID- 22647169
TI  - Martek instruments, inc.

PMID- 22647171
TI  - Oil recovery systems, inc.

PMID- 22647170
TI  - Acid deposition.

PMID- 22647172
TI  - Quality assurance, analytical methods, and hazardous wastes.

PMID- 22647173
TI  - EPA's new bubble and banking policies.

PMID- 22647174
TI  - Airborne remote sensing.

PMID- 22647176
TI  - Products.

PMID- 22647175
TI  - Specialized environmental equipment, inc.

PMID- 22647177
TI  - Foxboro.

PMID- 22647178
TI  - CHEMetrics, Inc.

PMID- 22647179
TI  - LIFE SUPPORT SYSTEMS Div. of Searle Medical Products USA, Inc.

PMID- 22647182
TI  - The Annual ACS LabGuide- the Definitive Source for.

PMID- 22647180
TI  - Isco.

PMID- 22647184
TI  - International.

PMID- 22647183
TI  - Courses.

PMID- 22647186
TI  - professional consulting services directory.

PMID- 22647187
TI  - Index to the advertisers in this issue.

PMID- 22647189
TI  - Qualitative and quantitative approaches in comprehensive two-dimensional gas
      chromatography.
AB  - Comprehensive two-dimensional gas chromatography (GC*GC) offers advantages over
      one-dimensional gas chromatography (GC) including, high peak capacity, signal
      enhancement, and structured chromatograms. These advantages have been exploited
      to solve several analytical problems that are difficult to achieve in GC. In this
      review, qualitative and quantitative approaches of GC*GC are explored, including
      targeted, non-targeted, group, and fingerprinting analysis.

PMID- 22647188
TI  - Development of a multi-residue method using acetonitrile-based extraction
      followed by liquid chromatography-tandem mass spectrometry for the analysis of
      steroids and veterinary and human drugs at trace levels in soil.
AB  - The aim of this study was to develop an analytical method for the analysis of
      traces of hormonal steroids and veterinary and human drugs in soil. Thus, 31
      substances were selected, including 14 veterinary products, 11 hormonal steroids
      and 6 other well-known human contaminant compounds. The procedure inspired by the
      quick, easy, cheap, effective, rugged and safe (QuEChERS) extraction method was
      developed. First the acetonitrile-based extraction was optimized. This step was
      followed by a solid-phase extraction (SPE) clean-up using both a strong anion
      exchange cartridge and a polymeric cartridge. The analysis was then performed
      using liquid chromatography coupled to a triple quadrupole analyser operated with
      tandem mass spectrometry. This analytical procedure was validated using the
      ICH/2005 standard by evaluating the linearity (from 0.01 ng/g to 1000 ng/g-
      R2>0.99), the intra-day precision (relative standard deviation (RSD)<20%), the
      inter-day precision (RSD<30%), recoveries (40-110% for most of the compounds) and
      limits of detection and quantification. This method allowed for the determination
      of the target analytes in the lower ng/g concentration range. The methodology was
      then applied to real soil samples collected in several areas of France that
      received different manure or sludge treatments. Some target compounds were
      detected at very low level (inferior to the ng/g). Veterinary antibiotics, mainly
      from the sulfonamide family, were found in soils treated by manure (0.02-0.12
      ng/g). On the other hand, pharmaceuticals usually used by humans (carbamazepine,
      ibuprofen) were detected in soils treated by domestic sludge.

PMID- 22647190
TI  - Characterization and use of hydrophilic interaction liquid chromatography type
      stationary phases in supercritical fluid chromatography.
AB  - All stationary phase chemistries are useful to achiral packed-column
      supercritical fluid chromatography (pSFC), but the majority of recent
      applications are based on polar stationary phases of the type used in normal
      phase HPLC. Some manufacturers have recently introduced pSFC-tailored stationary
      phases, while others simply advocate the use of selected HPLC columns among their
      brands for SFC use. Indeed, any column developed for HPLC use can be used with
      supercritical fluids. Besides, hydrophilic interaction liquid chromatography
      (HILIC) is facing an increasing interest. Consequently, a number of HILIC-devoted
      stationary phases are now commercialized by most column manufacturers. As HILIC
      stationary phases are polar, their possible use in pSFC seems obvious, although
      literature examples are not numerous. However, whether they provide acceptable
      peak shapes in SFC conditions is a serious concern for them to find
      applicability. Indeed, columns optimized for HILIC mobile phases may not be
      optimum for SFC mobile phases. We present the characterization of eleven HILIC
      type stationary phases used with carbon dioxide-methanol mobile phases in the
      isocratic mode. The columns are compared in terms of their retention and
      separation characteristics assessed by the solvation parameter model, and based
      on peak shapes. For this purpose, hundred and forty-six low molecular weight
      molecules, comprising neutral, basic and acidic compounds, were eluted on each
      column. Data analysis is carried out with hierarchical cluster analysis and
      principal component analysis in order to define three clusters of columns with
      similar selectivity: the first cluster comprises neutral stationary phases like
      amide and diol phases; the second one comprises basic stationary phases like
      aminopropyl-bonded silica; the last cluster comprises bare silica stationary
      phases. Sample applications with three different test mixtures relevant to
      pharmaceutical applications (barbiturates, benzodiazepines and propionic acids)
      are presented to assess the complementarity of some selected columns.

PMID- 22647191
TI  - Preparation and characterization of ceramic/carbon coated Fe3O4 magnetic
      nanoparticle nanocomposite as a solid-phase microextraction adsorbent.
AB  - A novel solid-phase microextraction (SPME) fiber based on a glass tube coated
      with ceramic/carbon coated Fe3O4 magnetic nanoparticle nanocomposite (C-Fe3O4/C
      MNP) was prepared by sol-gel technique. The carbon coated Fe3O4 magnetic
      nanoparticles were synthesized by a simple hydrothermal reaction and the
      resultant powder was mixed with sol-gel precursors to prepare C-Fe3O4/C MNP. The
      prepared C-Fe3O4/C MNP was deposited on surface of glass tubes as new substrate
      with a simple method. The results revealed that this procedure was a simple and
      reproducible technique for the preparation of SPME fibers coated with magnetic
      nanoparticles. The scanning electron micrographs of the fiber surface revealed a
      three-dimensional structure which is suitable as SPME adsorbents. Some polycyclic
      aromatic hydrocarbons (PAHs) were selected as model compounds for evaluating
      performance of the designed SPME fiber. The analytes were extracted with SPME,
      and desorbed using acetonitrile via ultrasonication. The extracts were analyzed
      by high performance liquid chromatography (HPLC) with fluorescence detection. The
      results demonstrated that the proposed method based on the C-Fe3O4/C MNP fiber
      had wide dynamic linear range (0.01-350 MUg L-1) with good linearity (R2>0.990)
      and low detection limits (0.7-50 pg mL-1). The relative standard deviation ranged
      from 6.9% to 12.2% for inter-day variations. These fibers were successfully used
      for the analysis of spiked water samples, which demonstrating the applicability
      of the home-made C-Fe3O4/C MNP fibers.

PMID- 22647193
TI  - Water evaporation on highly viscoelastic polymer surfaces.
AB  - Results are reported for a study on the evaporation of water droplets from a
      highly viscoelastic acrylic polymer surface. These are contrasted with those
      collected for the same measurements carried out on polydimethylsiloxane (PDMS).
      For PDMS, the evaporation process involves the expected multistep process
      including constant drop area, constant contact angle, and finally a combination
      of these steps until the liquid is gone. In contrast, water evaporation from the
      acrylic polymer shows a constant drop area mode throughout. Furthermore, during
      the evaporation process, the drop area actually expands on the acrylic polymer.
      The single mode evaporation process is consistent with formation of wetting
      structures, which cannot be propagated by the capillary forces. Expansion of the
      drop area is attributed to the influence of the drop capillary pressure.
      Furthermore, the rate of drop area expansion is shown to be dependent on the
      thickness of the polymer film.

PMID- 22647194
TI  - Predicting active school travel: the role of planned behavior and habit strength.
AB  - BACKGROUND: Despite strong support for predictive validity of the theory of
      planned behavior (TPB) substantial variance in both intention and behavior is
      unaccounted for by the model's predictors. The present study tested the extent to
      which habit strength augments the predictive validity of the TPB in relation to a
      currently under-researched behavior that has important health implications,
      namely children's active school travel. METHOD: Participants (N = 126 children
      aged 8-9 years; 59 % males) were sampled from five elementary schools in the west
      of Scotland and completed questionnaire measures of all TPB constructs in
      relation to walking to school and both walking and car/bus use habit. Over the
      subsequent week, commuting steps on school journeys were measured objectively
      using an accelerometer. Hierarchical multiple regressions were used to test the
      predictive utility of the TPB and habit strength in relation to both intention
      and subsequent behavior. RESULTS: The TPB accounted for 41 % and 10 % of the
      variance in intention and objectively measured behavior, respectively. Together,
      walking habit and car/bus habit significantly increased the proportion of
      explained variance in both intention and behavior by 6 %. Perceived behavioral
      control and both walking and car/bus habit independently predicted intention.
      Intention and car/bus habit independently predicted behavior. CONCLUSIONS: The
      TPB significantly predicts children's active school travel. However, habit
      strength augments the predictive validity of the model. The results indicate that
      school travel is controlled by both intentional and habitual processes. In
      practice, interventions could usefully decrease the habitual use of motorized
      transport for travel to school and increase children's intention to walk (via
      increases in perceived behavioral control and walking habit, and decreases in
      car/bus habit). Further research is needed to identify effective strategies for
      changing these antecedents of children's active school travel.

PMID- 22647192
TI  - Catalytic transitions in the human MDR1 P-glycoprotein drug binding sites.
AB  - Multidrug resistance proteins that belong to the ATP-binding cassette family like
      the human P-glycoprotein (ABCB1 or Pgp) are responsible for many failed cancer
      and antiviral chemotherapies because these membrane transporters remove the
      chemotherapeutics from the targeted cells. Understanding the details of the
      catalytic mechanism of Pgp is therefore critical to the development of inhibitors
      that might overcome these resistances. In this work, targeted molecular dynamics
      techniques were used to elucidate catalytically relevant structures of Pgp.
      Crystal structures of homologues in four different conformations were used as
      intermediate targets in the dynamics simulations. Transitions from conformations
      that were wide open to the cytoplasm to transition state conformations that were
      wide open to the extracellular space were studied. Twenty-six nonredundant
      transitional protein structures were identified from these targeted molecular
      dynamics simulations using evolutionary structure analyses. Coupled movement of
      nucleotide binding domains (NBDs) and transmembrane domains (TMDs) that form the
      drug binding cavities were observed. Pronounced twisting of the NBDs as they
      approached each other as well as the quantification of a dramatic opening of the
      TMDs to the extracellular space as the ATP hydrolysis transition state was
      reached were observed. Docking interactions of 21 known transport ligands or
      inhibitors were analyzed with each of the 26 transitional structures. Many of the
      docking results obtained here were validated by previously published biochemical
      determinations. As the ATP hydrolysis transition state was approached, drug
      docking in the extracellular half of the transmembrane domains seemed to be
      destabilized as transport ligand exit gates opened to the extracellular space.

PMID- 22647195
TI  - DNA damage and biochemical toxicity of antibiotics in soil on the earthworm
      Eisenia fetida.
AB  - DNA damage and changes in enzyme activities were used as biomarkers to evaluate
      the genotoxicity and oxidative stress of tetracycline and chlortetracycline on
      the earthworm Eisenia fetida. The results showed that both antibiotics induced
      significant genotoxicity on earthworms in a dose-dependent manner (p<0.01) with
      chlortetracycline having a stronger effect than tetracycline in the short term.
      The tests on the activities of superoxide dismutase (SOD) and catalase (CAT)
      enzymes further indicated biochemical stresses induced by the antibiotics. An N
      shaped activity pattern was noted with the enzyme activities being stimulated
      first, then inhibited, and stimulated again with increasing concentration. The
      induced activity of SOD or CAT could scavenge oxygen free radicals and protect
      the organisms against oxidative stress by alleviating the corresponding DNA
      damage. Compared to enzyme activities, DNA damage as a biomarker was more
      sensitive and is thus more suitable for detecting low concentration exposure and
      diagnosing the genotoxicity of contaminants in terrestrial environment.

PMID- 22647196
TI  - Biodegradation of pentaerythritol tetranitrate (PETN) by anaerobic consortia from
      a contaminated site.
AB  - This study examined the role of denitrifying and sulfate-reducing bacteria in
      biodegradation of pentaerythritol tetranitrate (PETN). Microbial inocula were
      obtained from a PETN-contaminated soil. PETN degradation was evaluated using
      nitrate and/or sulfate as electron acceptors and acetate as a carbon source.
      Results showed that under different electron acceptor conditions tested, PETN was
      sequentially reduced to pentaerythritol via the intermediary formation of tri-,
      di- and mononitrate pentaerythritol (PETriN, PEDN and PEMN). The addition of
      nitrate enhanced the degradation rate of PETN by stimulating greater microbial
      activity and growth of nitrite reducing bacteria that were responsible for
      degrading PETN. However, a high concentration of nitrite (350mgL(-1)) accumulated
      from nitrate reduction, consequently caused self-inhibition and temporarily
      delayed PETN biodegradation. In contrast, PETN degraded at very similar rates in
      the presence and absence of sulfate, while PETN inhibited sulfate reduction. It
      is apparent that denitrifying bacteria possessing nitrite reductase were capable
      of using PETN and its intermediates as terminal electron acceptors in a
      preferential utilization sequence of PETN, PETriN, PEDN and PEMN, while sulfate
      reducing bacteria were not involved in PETN biodegradation. This study
      demonstrated that under anaerobic conditions and with sufficient carbon source,
      PETN can be effectively biotransformed by indigenous denitrifying bacteria,
      providing a viable means of treatment for PETN-containing wastewaters and PETN
      contaminated soils.

PMID- 22647197
TI  - Developing leadership capacity for guideline use: a pilot cluster randomized
      control trial.
AB  - SIGNIFICANCE: The importance of leadership to influence nurses' use of clinical
      guidelines has been well documented. However, little is known about how to
      develop and evaluate leadership interventions for guideline use. PURPOSE: The
      purpose of this study was to pilot a leadership intervention designed to
      influence nurses' use of guideline recommendations when caring for patients with
      diabetic foot ulcers in home care nursing. This paper reports on the feasibility
      of implementing the study protocol, the trial findings related to nursing process
      outcomes, and leadership behaviors. METHODS: A mixed methods pilot study was
      conducted with a post-only cluster randomized controlled trial and descriptive
      qualitative interviews. Four units were randomized to control or experimental
      groups. Clinical and management leadership teams participated in a 12-week
      leadership intervention (workshop, teleconferences). Participants received
      summarized chart audit data, identified goals for change, and created a team
      leadership action. Criteria to assess feasibility of the protocol included:
      design, intervention, measures, and data collection procedures. For the trial,
      chart audits compared differences in nursing process outcomes. PRIMARY OUTCOME: 8
      item nursing assessments score. Secondary outcome: 5-item score of nursing care
      based on goals for change identified by intervention participants. Qualitative
      interviews described leadership behaviors that influenced guideline use. RESULTS:
      Conducting this pilot showed some aspects of the study protocol were feasible,
      while others require further development. Trial findings observed no significant
      difference in the primary outcome. A significant increase was observed in the 5
      item score chosen by intervention participants (p = 0.02). In the experimental
      group more relations-oriented leadership behaviors, audit and feedback and
      reminders were described as leadership strategies. CONCLUSIONS: Findings suggest
      that a leadership intervention has the potential to influence nurses' use of
      guideline recommendations, but further work is required to refine the
      intervention and outcome measures. A taxonomy of leadership behaviors is proposed
      to inform future research.

PMID- 22647199
TI  - Computational study of the enantioselective deprotonation of a
      cyclopropanecarboxamide with an alkyllithium in the presence of sparteine.
AB  - The enantioselective deprotonation of N,N-diisopropy-1
      methylcyclopropanecarboxamide (2) with i-PrLi-(-)-sparteine has been studied at
      theoretical levels up through B3LYP/6-311+G*. Thirty-six conformationally
      flexible intermediate complexes involving i-PrLi-(-)-sparteine and 2 were located
      via geometry optimizations The lowest energy complex would lead to abstraction of
      the pro-S hydrogen from 2, and several higher energy complexes would lead to loss
      of the pro-R hydrogen. The lowest energy complex was found to have the lowest
      activation energy leading to loss of the pro-S hydrogen of 2 as observed
      experimentally. The results demonstrate that the conformations of the N,N
      diisopropyl groups in the amide moiety of 2 have a large effect on the
      enantioselectivity of the lithiation.

PMID- 22647198
TI  - Current routines for transrectal ultrasound-guided prostate biopsy: a web-based
      survey by the Swedish Urology Network.
AB  - OBJECTIVE: This study aimed to survey current Swedish practices for performing
      and handling transrectal ultrasound-guided prostate biopsies. MATERIAL AND
      METHODS: A Swedish Urology Network (SUNe) was organized for the distribution of
      information, survey studies and research collaborations. A web-based
      questionnaire was distributed to the members in 2011. RESULTS: In this first SUNe
      survey, 137 (91%) of the 151 members replied. All used antibiotic prophylaxis
      (84% ciprofloxacin, 12% trimethoprim-sulfamethoxazole), most commonly (63%) as a
      single dose of ciprofloxacin. Local anaesthesia was used by 87%. Half of the
      respondents only used a "side-fire" probe, whereas 17% always used an "end-fire"
      probe. Most (84%) routinely took 10 or more biopsy cores. About three-quarters
      started with the right base of the prostate and did not routinely take midline
      biopsies. More than one-third never or rarely sampled the anterior part of the
      prostate. There was great variability in how biopsy location was reported, but
      71% considered a national standardized coordinate system desirable. Fine-needle
      aspiration was used occasionally by 39%, in more than 10% of cases by 6% and
      always by 2%. Most urologists mounted the biopsy cores on paper before fixation
      (78%), put only one core per jar (75%) and used flat-bottomed jars (70%).
      CONCLUSIONS: Most routines for handling of prostate biopsies, antibiotic
      prophylaxis, local anaesthesia and number of cores were uniform. However, there
      is still a need for standardization of the performance of ultrasound-guided
      biopsies. Although the method used to specify biopsy location varied greatly,
      most urologists would prefer a national standardized system.

PMID- 22647200
TI  - How can we enable drug discovery informatics for personalized healthcare?
AB  - Individualized treatment selection based on scientific results is set to be the
      future of healthcare. It will not only have a significant favorable impact on the
      health of patients suffering from various diseases, but also on how drug
      discovery is performed. Previously unobserved information will be generated,
      facilitating much deeper disease insight on an individual level than was feasible
      before. Without a doubt, this will also lead to major consequences for
      informatics as it is necessary to deal with numerous novel and constantly
      changing information types and requirements. One central concern will be
      addressing the scale of data flooding in, but much more important will be
      bringing together the complexity of available data enabling scientists to
      successfully generate meaningful hypotheses and results. This will then help in
      aiming for an understanding of disease phenomena as a whole, and not only
      fragments within drug discovery. Informatics needs to be the key enabler for the
      entire process. This contribution aims to show a possible route for approaching
      this in a future-proof way, leveraging and adapting knowledge-sharing approaches.

PMID- 22647201
TI  - The quest for novel chemical matter and the contribution of computer-aided de
      novo design.
AB  - Identifying novel chemical matter is the focus of many drug discovery efforts.
      Through these efforts, computer-based de novo design of drug-like molecules,
      which aim to build an entire molecule 'from scratch', has emerged as a valuable
      approach to identify novel chemical matter. In this paper, the author discusses
      the recent research efforts that aim to build, in silico, more chemically
      accessible molecules, sample more efficiently the chemical space and rank the
      proposed molecules. The author reviews de novo design algorithms developed
      between 2008 and 2010 and the issue of validation, and highlights some recent
      successful applications of de novo design to drug discovery projects. Although
      research has addressed the lack of synthetic accessibility of the molecules
      proposed by the first generation of de novo design tools, the lack of accurate
      scoring function remains a major limitation of structure-based de novo design.
      However, de novo design is a valuable approach to generate either chemical
      starting points or ideas.

PMID- 22647202
TI  - Nonhuman primates as models for the discovery and development of ebolavirus
      therapeutics.
AB  - INTRODUCTION: Ebolaviruses are human pathogenic Category A priority pathogens for
      which no vaccines or therapeutics are currently licensed; however, several
      therapeutic agents have shown promising efficacy in nonhuman primate models of
      infection and are potential candidates for use in humans. Demonstration of
      efficacy in nonhuman primate models of ebolavirus infection will probably be
      central to the development and eventual licensure of ebolavirus medical
      countermeasures given the ethical and feasibility constraints of human efficacy
      assessments. AREAS COVERED: The authors describe ebolavirus hemorrhagic fever
      (EHF), with an emphasis on comparing human and nonhuman primate pathophysiology.
      Published data examining human and animal clinical disease parameters,
      histopathological findings, and immune responses in fatal and nonfatal cases are
      synthesized and evaluated. Importantly, the authors also introduce and describe
      the FDA Animal Efficacy Rule as well as recent advances in antiviral drug
      development strategies for the treatment of EHF. EXPERT OPINION: Well
      characterized models of ebolavirus infection are currently under development and
      scrutiny as to their accuracy and utility for modeling fatal infection in humans.
      The advanced development and eventual licensure of therapeutic agents will
      require demonstration that mechanisms conferring protection in nonhuman primate
      models of infection are predictive of protective responses in humans.

PMID- 22647203
TI  - The concept of privileged structures in rational drug design: focus on acridine
      and quinoline scaffolds in neurodegenerative and protozoan diseases.
AB  - INTRODUCTION: For nearly 20 years, privileged structures have offered an optimal
      source of core scaffolds and capping fragments for the design of combinatorial
      libraries directed at a broad spectrum of targets. From describing structures
      promiscuous within a given target family, the concept has evolved to include
      frameworks that can modulate proteins lacking a strict target class relation.
      AREAS COVERED: Based on a literature search from 2000 to 2010, we discuss how two
      privileged motifs, quinolines and acridines, are particularly recurrent in
      compounds active against two quite different pathologies, neurodegenerative and
      protozoan diseases. EXPERT OPINION: As privileged structures, quinolines and
      acridines could improve the productivity of drug discovery projects in the field
      of neurodegenerative and protozoan diseases. They could be particularly relevant
      for protozoan diseases because of the importance of cost-effective strategies and
      less stringent intellectual property concerns. Furthermore, because of their
      inherent affinity for various targets, privileged structures could offer a viable
      starting point in the search for novel multi-target ligands. Finally, from a
      broader perspective, they can serve as effective probes for investigating unknown
      but interrelated mechanisms of action.

PMID- 22647204
TI  - Small interfering ribonucleic acid design strategies for effective targeting and
      gene silencing.
AB  - INTRODUCTION: Gene silencing mediated by siRNAs is becoming a promising
      therapeutic approach. Although many strategies and technologies have been applied
      to siRNA design, a key issue lies in the selection of efficient design
      predictors. Furthermore, the development of systemic siRNA delivery strategies,
      which would enhance the therapeutic effect, remains a central issue. AREAS
      COVERED: The review discusses the basic principles of the sequence-specific
      design criteria of functional siRNAs and possible chemical modifications. Some of
      the most recent advances in the development of siRNA design algorithms and
      delivery strategies are also presented. Emphasis is given to the important design
      rule sets and predictors which determine the functionality of an efficient siRNA.
      EXPERT OPINION: The potential and limitations of efficient design predictors
      obtained from computational algorithms play a crucial role in the development of
      target-specific siRNAs. Furthermore, the future success of RNA interference
      therapeutics will depend on their ability to efficiently cross the physiological
      barriers, selectively target cells-of-interest and finally silence the gene-of
      interest without any side effects.

PMID- 22647205
TI  - Techniques for the discovery and evaluation of drugs against alopecia.
AB  - INTRODUCTION: Hair care, color and style play an important role in physical
      appearance and self-perception. Hair loss or alopecia is a common dermatological
      and affective disorder. Factors contributing to alopecia include genetic
      predisposition, hormonal factors, disease status, side effects of
      chemotherapeutic agents and stress. To keep pace with the demand for drugs for
      alopecia, attempts are being made to explore drugs with hair-growth-promotion
      activity. To explore and evaluate these, it is necessary to be familiar with the
      basics and the availability and suitability of techniques and experimental models
      of hair growth activity assessment. AREAS COVERED: Basic and advanced techniques
      and models for assessing hair growth activity. A variety of pharmacological
      models of hair growth are reviewed. This review will help in selecting a
      suitable, relevant, inexpensive, easy and reliable model for hair growth
      assessment. EXPERT OPINION: There is a need to identify the genes involved in
      hair follicle growth for the production of more effective animal models of the
      disorder. Standardization of pharmacological models will also be essential for
      better comparison and validation of results. Recently developed hair follicle
      organ culture models are a suitable, relevant and inexpensive alternative to
      traditional whole-animal pharmacological models and will, largely, replace whole
      animal systems in the future.

PMID- 22647206
TI  - Research and innovation in the development of everolimus for oncology.
AB  - INTRODUCTION: The critical role of increased activity of mammalian target of
      rapamycin (mTOR) in the pathophysiology of multiple diseases is well established.
      Inhibition of the mTOR pathway may block disease progression and improve patient
      outcomes. Everolimus, an mTOR inhibitor, began in clinical development as part of
      a regimen (Certican, Zortress) for prevention of organ transplant rejection and
      is now an approved oncology agent. AREAS COVERED: The objective of this review is
      to discuss the history of key findings and innovative cancer research undertaken
      to successfully develop everolimus as an oncology therapy (Afinitor) now approved
      for patients with advanced renal cell carcinoma (RCC) and for subependymal giant
      cell astrocytomas (SEGAs) associated with tuberous sclerosis. In addition, data
      for the use of everolimus in the treatment of other cancers and rare diseases are
      also discussed. A PubMed search of English articles without time restrictions was
      conducted using the search terms 'everolimus or rapamycin' and 'cancer'.
      Bibliographies of retrieved articles were manually searched for additional
      relevant articles. Major cancer congresses were also searched. EXPERT OPINION:
      The clinical efficacy of everolimus alone and in combination with other agents
      has been observed in recently completed Phase II-III studies in a wide spectrum
      of tumors, including RCC, neuroendocrine tumors, tuberous sclerosis complex,
      SEGAs and angiomyolipomas, lymphoma and gastric, breast and hepatocellular
      cancers. These findings emphasize the importance of mTOR in diverse cancers and
      rare diseases and underscore the potential role for everolimus as an effective
      agent in multiple indications.

PMID- 22647207
TI  - Three-dimensional structure generators of drug-like compounds: DG-AMMOS, an open
      source package.
AB  - INTRODUCTION: Drug discovery is a time consuming and costly process. Thus, a
      trend towards the use of in silico approaches such as structure- and ligand-based
      virtual screening methods to speed up the process has gained significant momentum
      in recent years. Most of these in silico applications require a good quality 3D
      structure of the small drug-like molecules as input. AREAS COVERED: This article
      reviews the algorithm and validation of the open-source software DG-AMMOS, a tool
      that generates the 3D conformation of small molecules using distance geometry
      construction and molecular mechanics optimization comparing its performance with
      some related free and commercial packages. EXPERT OPINION: The number of
      chemo/bioinformatics free and/or open-source tools assisting drug discovery
      projects is increasing, and many successful contributions making use of these
      computer programs have been reported. DG-AMMOS is an efficient 3D structure
      generator engine that provides fast and reliable generation of 3D structures and
      contributes to the preparation of a compound collection. DG-AMMOS can still be
      improved and an increased speed and user-friendly interface in addition to the
      implementation of workflow engines will increase its effectiveness.

PMID- 22647209
TI  - The subtleties of scientific writing.

PMID- 22647210
TI  - The effect of neutering on the risk of mammary tumours in dogs--a systematic
      review.
AB  - A commonly-stated advantage of neutering bitches is a significant reduction in
      the risk of mammary tumours, however the evidence for this has not previously
      been assessed by systematic review. The objectives of this study were to estimate
      the magnitude and strength of evidence for any effect of neutering, or age of
      neutering, on the risk of mammary tumours in bitches. A systematic review was
      conducted based on Cochrane guidelines. Peer-reviewed analytic journal articles
      in English were eligible and were assessed for risk of bias by two reviewers
      independently. Of 11,149 search results, 13 reports in English-language peer
      reviewed journals addressed the association between neutering/age at neutering
      and mammary tumours. Nine were judged to have a high risk of bias. The remaining
      four were classified as having a moderate risk of bias. One study found an
      association between neutering and a reduced risk of mammary tumours. Two studies
      found no evidence of an association. One reported "some protective effect" of
      neutering on the risk of mammary tumours, but no numbers were presented. Due to
      the limited evidence available and the risk of bias in the published results, the
      evidence that neutering reduces the risk of mammary neoplasia, and the evidence
      that age at neutering has an effect, are judged to be weak and are not a sound
      basis for firm recommendations.

PMID- 22647208
TI  - AlzPathway: a comprehensive map of signaling pathways of Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia among
      the elderly. To clarify pathogenesis of AD, thousands of reports have been
      accumulating. However, knowledge of signaling pathways in the field of AD has not
      been compiled as a database before. DESCRIPTION: Here, we have constructed a
      publicly available pathway map called "AlzPathway" that comprehensively catalogs
      signaling pathways in the field of AD. We have collected and manually curated
      over 100 review articles related to AD, and have built an AD pathway map using
      CellDesigner. AlzPathway is currently composed of 1347 molecules and 1070
      reactions in neuron, brain blood barrier, presynaptic, postsynaptic, astrocyte,
      and microglial cells and their cellular localizations. AlzPathway is available as
      both the SBML (Systems Biology Markup Language) map for CellDesigner and the high
      resolution image map. AlzPathway is also available as a web service (online map)
      based on Payao system, a community-based, collaborative web service platform for
      pathway model curation, enabling continuous updates by AD researchers.
      CONCLUSIONS: AlzPathway is the first comprehensive map of intra, inter and extra
      cellular AD signaling pathways which can enable mechanistic deciphering of AD
      pathogenesis. The AlzPathway map is accessible at http://alzpathway.org/.

PMID- 22647211
TI  - Conventional and Doppler ultrasound for the differentiation of benign and
      malignant canine mammary tumours.
AB  - OBJECTIVES: The aim of this study was to evaluate the sensitivity of conventional
      and Doppler ultrasound for differentiation of benign and malignant mammary
      tumours in female dogs. METHODS: Mammary tumours were evaluated from 60 animals
      and divided into two distinct groups, group 1 (benign tumours) and group 2
      (malignant tumours). The tumours were assessed by conventional ultrasound,
      Doppler ultrasound mode, histopathology and immunohistochemical detection of
      vascular endothelial growth factor. RESULTS: Conventional ultrasound examination
      was found to be ineffective in separating tumours into the two experimental
      groups. Similarly, using colour-flow Doppler ultrasound, no correlation was found
      between the presence of vascularisation and its characteristics between the two
      groups. Triplex Doppler ultrasound yielded average maximum velocities of 28.71
      cm/s for malignant and 19.91 cm/s for benign tumours, which were significantly
      different (P=0.01). For vascular endothelial growth factor, an average score of
      2.22 was found for group 2 and 1.66 for group 1 (P=0.03). Positive correlations
      were found between vascular endothelial growth factor and presence of
      vascularisation (P=0.04 and r=0.3658) and between vascular endothelial growth
      factor and maximum velocity (P=0.03 and r=0.3913). CLINICAL SIGNIFICANCE: Doppler
      evaluation may be used to predict malignancy of mammary tumours in bitches.

PMID- 22647212
TI  - Static hydraulic urethral sphincter for treatment of urethral sphincter mechanism
      incompetence in 11 dogs.
AB  - OBJECTIVE: To review the postoperative results and complications associated with
      urethral sphincter mechanism incompetence managed with a static hydraulic
      urethral sphincter. METHODS: Case records and a telephone owner questionnaire
      were retrospectively used to assess postoperative urinary continence scores (1 -
      dripping constantly to 10 - completely dry) and presence and frequency of
      complications. RESULTS: Eleven spayed females were included. Median continence
      score/10 (range) awarded preoperatively was 3 (2 to 6), and scores at two weeks,
      three and six months were 8 (4 to 10), 9 (4 to 10) and 8 (4 to 10), respectively.
      At the last survey, the median continence score of 9 (5 to 10) was significantly
      better (P=0.004) than before surgery. Complete continence was achieved in 36.4%
      of dogs. The median (range) follow-up time was 412 (118 to 749) days.
      Complications occurred in 9 of 11 dogs and included dysuria (n=7), bacterial
      cystitis (n=7), longer urination time (n=8), urinary retention (n=3), haematuria
      (n=1), pain (n=3) and incisional seroma (n=3). CLINICAL SIGNIFICANCE: Static
      hydraulic urethral sphincter was frequently associated with minor complications
      but no major complications (i.e. those requiring further surgery). Continence
      scores were significantly improved compared with those before surgery, with the
      possibility of further improvement following inflation of the sphincter.

PMID- 22647213
TI  - Clinical evaluation of cochlear hearing status in dogs using evoked otoacoustic
      emissions.
AB  - OBJECTIVES: Evoked otoacoustic emission testing is the preferred test in human
      patients for sensorineural deafness screening in neonates and cochlear outer hair
      cell function monitoring in adults. This study evaluated evoked otoacoustic
      emission testing for cochlear function assessment in dogs within a clinical
      setting. METHODS: Two populations of anaesthetised dogs were included. In group 1
      the evoked otoacoustic emission response was compared to the brainstem auditory
      evoked response in 10 dogs having hearing assessment. Group 2 comprised 43
      presumed normal dogs, in which the suitability of two types of evoked otoacoustic
      emissions, transient-evoked and distortion product otoacoustic emissions, were
      evaluated (brainstem auditory evoked response was not performed in this group).
      RESULTS: Valid transient-evoked otoacoustic emission and distortion-product
      otoacoustic emission responses were successfully recorded within the clinical
      setting and correctly identified deaf and hearing ears. Within presumed healthy
      dogs, normal otoacoustic emission response was demonstrated in more than 80% of
      dogs using a single, short distortion-product otoacoustic emission run and in 78%
      of dogs with valid transient-evoked otoacoustic emission responses using a series
      of three repeated transient-evoked otoacoustic emission short runs. CLINICAL
      SIGNIFICANCE: Transient-evoked otoacoustic emission and distortion-product
      otoacoustic emission testing provided a rapid, non-invasive frequency-specific
      assessment of cochlear function. Transient-evoked otoacoustic emission and
      distortion product otoacoustic emission testing is suitable as a screening
      procedure to detect loss of cochlear function in dogs, although further
      investigation is needed.

PMID- 22647214
TI  - Adult-onset nemaline myopathy in a dog presenting with persistent atrial
      standstill and primary hypothyroidism.
AB  - A nine-year-old neutered female mixed breed dog presented for evaluation
      following a five-day history of lethargy, inappetence, weakness, abdominal
      distension and generalised muscle atrophy. Persistent vatrial standstill with a
      junctional rhythm was identified on electrocardiogram. Echocardiogram identified
      moderate dilation of all cardiac chambers and mild thickening of the mitral and
      tricuspid valves. Serology was negative for Neospora caninum and Toxoplasma
      gondii. Permanent pacemaker implantation was performed in addition to
      endomyocardial and skeletal muscle biopsies. Cryosections from the biceps femoris
      muscle showed numerous nemaline rod bodies while endomyocardial biopsies were
      possibly consistent with end-stage myocarditis. Rod bodies have rarely been
      reported in the veterinary literature. To the authors' knowledge, this is the
      first report of adult-onset nemaline rod myopathy and hypothyroidism with
      concurrent cardiac disease in a dog.

PMID- 22647215
TI  - Rhinolithiasis in two miniature dogs.
AB  - This case report describes two dogs, a Chihuahua and a Pekingese each with
      rhinolithiasis. Both dogs were presented with chronic nasal obstruction and
      discharge. Rhinoliths were noted on computed tomography scans in both animals,
      and removed via endoscopic extraction in one case and laser-assisted endoscopic
      surgery in the other. The stone from the Chihuahua comprised calcium carbonate. A
      potential exogenous nidus in the form of plant material was identified in the
      Pekingese. To the authors' knowledge, this is the first report of rhinolithiasis
      in veterinary medicine.

PMID- 22647217
TI  - Discovery and structure-activity analysis of selective estrogen receptor
      modulators via similarity-based virtual screening.
AB  - A number of selective estrogen receptor modulators (SERMs) were discovered from
      the SPECS database via a simple protocol. Based on two reference SERMs we
      identified via structure-based virtual screening previously, ligand-based
      similarity search and molecular docking filtering were conducted to identify
      novel SERMs from SPECS library. Among the 36 purchased compounds, 21 were
      confirmed to be active by in vitro assays, and 10 showed dual profile properties,
      namely as antagonists of ERalpha and agonists of ERbeta. The anti-proliferative
      potency of these ligands was also evaluated against MCF-7 cell lines. Further
      investigation of the anti-proliferative mechanism of compound 3a suggested that
      it induced a G1 cell cycle arrest in ERalpha positive MCF-7 cell through ERalpha
      mediated cyclin D1 down-regulation.

PMID- 22647218
TI  - Heterocycle-functional gramine analogues: solvent- and catalyst-free synthesis
      and their inhibition activities against cell proliferation.
AB  - A series of novel gramine analogues were designed and synthesized via a
      convenient three-component reaction, and which were evaluated for their
      inhibition activities against cell proliferation. Their structures were confirmed
      by satisfactory spectra analyses mainly including (1)H NMR, and ESI-MS analyses.
      The preliminary assays indicated that some of the newly synthesized compounds
      displayed significantly good inhibition activities against human lung cancer (NCI
      H460), hepatocellular liver carcinoma (HepG2), gastric cancer (SGC-7901 and BGC
      823) cell lines compared with the control 5-Fluorouracil (5-FU), which might be
      developed as novel lead scaffold for potential anticancer agents.

PMID- 22647219
TI  - Docking, synthesis and pharmacological activity of novel urea-derivatives
      designed as p38 MAPK inhibitors.
AB  - p38 mitogen-activated protein kinase (p38 MAPK) is an important signal
      transducing enzyme involved in many cellular regulations, including signaling
      pathways, pain and inflammation. Several p38 MAPK inhibitors have been developed
      as drug candidates to treatment of autoimmune disorders, such as rheumatoid
      arthritis. In this paper we reported the docking, synthesis and pharmacological
      activity of novel urea-derivatives (4a-e) designed as p38 MAPK inhibitors. These
      derivatives presented good theoretical affinity to the target p38 MAPK, standing
      out compound 4e (LASSBio-998), which showed a better score value compared to the
      prototype GK-00687. This compound was able to reduce in vitro TNF-alpha
      production and was orally active in a hypernociceptive murine model sensible to
      p38 MAPK inhibitors. Otherwise, compound 4e presented a dose-dependent analgesic
      effect in a model of antigen (mBSA)-induced arthritis and anti-inflammatory
      profile in carrageenan induced paw edema, indicating its potential as a new
      antiarthritis prototype.

PMID- 22647220
TI  - In vitro and in vivo biological evaluation of new 4,5-disubstituted 1,2,3
      triazoles as cis-constrained analogs of combretastatin A4.
AB  - To find new and better antivascular agents for cancer therapy, a series of
      combretastatin A4 (CA4) analogs were prepared from 1,3-diaryl-2-nitroprop-1-enes
      (6-12) obtained in a two-step synthesis from appropriate arylaldehydes and 2-aryl
      1-nitroethanes (4 or 5). Treatment of these 1,3-diaryl-2-nitroprop-1-enes 6-12 by
      sodium azide in DMSO yielded the targeted compounds. The synthesized 1,2,3
      triazoles disubstituted in 4- and 5-positions by one benzyl group and one aryl
      nucleus have also been tested for biological activities involved in antivascular
      action. It was found that several new compounds exhibited interesting biological
      activities in the nanomolar or low micromolar range, in terms of rounding up of
      endothelial cells, inhibition of tubulin polymerization, and cytotoxicity on B16
      melanoma cancer cells. In silico docking studies of 11 and 19 within the active
      site of tubulin were also carried out in order to rationalize the inhibitory
      properties of these compounds and further understand their inhibition mechanism.
      In vivo evaluation of compounds 11 and 19 in mice bearing colon 26 carcinoma
      indicated modest anticancer activity.

PMID- 22647221
TI  - Synthesis and pharmacological activity of N-(2,2-dimethyl-3,4-dihydro-2H-1
      benzopyran-4-yl)-4H-1,2,4-benzothiadiazine-3-carboxamides 1,1-dioxides on rat
      uterus, rat aorta and rat pancreatic beta-cells.
AB  - N-(2,2-Dimethyl-3,4-dihydro-2H-1-benzopyran-4-yl)-4H-1,2,4-benzothiadiazine-3
      carboxamides 1,1-dioxides were prepared and evaluated on rat uterus, rat aortic
      rings and rat pancreatic beta-cells. Pharmacological studies conducted on rat
      uterus indicated that several of these original hybrid compounds displayed a
      strong myorelaxant activity. The most active compounds hold a bromine atom at the
      6-position of the dihydrobenzopyran ring. Moreover, the compounds failed to
      display a marked inhibitory effect on insulin secretion and vascular myogenic
      activity. These features suggest that the 6-bromo compounds could be relatively
      selective towards the uterine smooth muscle.

PMID- 22647222
TI  - Synthesis and biological evaluation of new homocamptothecin analogs.
AB  - In order to increase the stability of E-ring of homocamptothecins, the electron
      withdrawing group -OH or -OAc was induced to alpha position of ring-E lactone.
      Ten new homocamptothecin analogs were synthesized. Most compounds showed potent
      in vitro anticancer activity and potent Topo I inhibition, which was equal or
      superior to that of CPT, SN-38 and 10-HCPT. The stability studies of this series
      also displayed significant improvement of the stability.

PMID- 22647224
TI  - Multi-Lorentzian representation of deuterium spectrum to study water spin
      magnetization exchange in MCM-41.
AB  - Water behavior on the pore surface of nano-silica MCM-41, at a hydration level
      corresponding to one water molecule per OH group, is studied using (2)H NMR
      spectra in the temperature range 213 to 313 K. In an earlier study [J. Hassan, E.
      Reardon, H. Peemoeller, Microporous Mesoporous Materials, 122 (2009) 121-127] it
      was shown that at this hydration level, deuterons of water at single OH sites
      exhibit a Lorentzian line shape and deuterons of water at hydrogen-bonded OH
      sites exhibit a powder pattern. Here it is shown that magnetization exchange
      occurs between these two deuteron spin groups. This exchange cannot be described
      using the common, two-site exchange model, involving two Lorentzians. We
      successfully apply a multi-Lorentzian exchange model, prompted by Woessner's work
      [D. E. Woessner, Mol. Phys. 34, 4, (1977) 899-920] on the effects of motion on
      the shape of water spin resonance lines exhibiting doublet splitting. For this
      low hydration sample the rate of magnetization exchange out of the hydration
      site, where the water deuterons exhibit a Lorentzian line in the (2)H spectra, is
      1.3 ms(-1) and the activation energy for the exchange is found to be 3.4+/-0.1
      kcal/mole.

PMID- 22647223
TI  - Metabolism-based synthesis, biologic evaluation and SARs analysis of O-methylated
      analogs of quercetin as thrombin inhibitors.
AB  - In blood, quercetin is mainly found in metabolized forms. In order to study the
      activities of these quercetin metabolites in cardiovascular disease, 17
      methylquercetin derivatives were synthesized based on metabolism in vivo, their
      thrombin inhibition activity were evaluated through the analyzation of
      prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin
      time (TT) and fibrinogen (FIB). The results showed that 6 methylquercetin
      derivatives had stronger inhibitory activities than that of quercetin.
      Preliminary SARs analysis showed that hydroxyl groups at C-3' and C-4' position
      in the B-ring and hydroxyl group at C-3 position in the C-ring played key roles
      in the thrombin inhibitory activity. The findings of this study would provide
      information for the exploitation and utilization of quercetin as thrombin
      inhibitor for thrombotic disease treatment.

PMID- 22647225
TI  - POLG mutations in Australian patients with mitochondrial disease.
AB  - BACKGROUND/AIM: The nuclear POLG gene encodes the catalytic subunit of DNA
      polymerase gamma (polgamma), the only polymerase involved in the replication and
      proofreading of mitochondrial DNA. As a consequence, POLG mutations can cause
      disease through impaired replication of mitochondrial DNA. To date, over 150
      different mutations have been identified, with a growing number of associated
      phenotypes described. The aim of this study was to determine the prevalence of
      POLG mutations in an adult population of Australian patients with mitochondrial
      disease, displaying symptoms commonly associated with POLG-related diseases.
      METHODS: The clinical presentations of 322 patients from a specialist adult
      mitochondrial disease clinic were reviewed. Nineteen exhibited a cluster of three
      or more predefined clinical manifestations suggestive of POLG-related disease:
      progressive external ophthalmoplegia, seizures and/or an abnormal
      electroencephalogram, neuropathy, ataxia, liver function abnormalities, migraine
      or dysphagia/dysarthria. Patients were screened for mutations by direct
      nucleotide sequencing of the coding and exon-flanking intronic regions of POLG.
      RESULTS: Five of the 19 patients (26%) displaying a phenotype suggestive of POLG
      related disease were found to have informative POLG coding mutations (p.T851A,
      p.N468D, p.Y831C, p.G517V and novel p.P163S variant). Literature and analysis of
      these mutations revealed that two of these patients had pathogenic mutations
      known to cause POLG-related disease (patient #1: p.T851A and p.P163S; patient #2:
      p.T851A and p.N468D). CONCLUSIONS: We conclude that the prevalence of pathogenic
      POLG mutations in our selected adult Australian cohort with suggestive clinical
      manifestations was 10%. A further 16% of patients had POLG variants but are
      unlikely to be responsible for causing their disease.

PMID- 22647226
TI  - Older people dying with dementia: a nationwide study.
AB  - BACKGROUND: Large-scale nationwide data describing the end-of-life
      characteristics of older people with dementia are lacking. This paper describes
      the dying process and end-of-life care provided to elderly people with mild or
      severe dementia in Belgium. It compares with elderly people dying without
      dementia. METHODS: A nationwide retrospective mortality study was conducted, via
      representative network of general practitioners (GPs) in 2008 in Belgium, with
      weekly registration of all deaths (aged >= 65) using a standardized form. GPs
      reported on diagnosis and severity of dementia, aspects of end-of-life care and
      communication, and on the last week of life in terms of symptoms that caused
      distress as judged by the GP, and the patients' physical and cognitive abilities.
      RESULTS: Thirty-one percent of our sample (1,108 deaths) had dementia (43%
      mildly, 57% severely). Of those, 26% died suddenly, 59% in care home, and 74%
      received palliative treatment, versus 37%, 19%, and 55% in people without
      dementia. GP-patient conversations were less frequent among those with (45%) than
      those without (73%) dementia, and 11% of both groups had a proxy decision-maker.
      During the last week of life, physical and psychological distress was common in
      both groups. Of older people with dementia, 83% were incapable of decision-making
      and 83% were bedridden; both significantly higher percentages than found in the
      group without dementia (24% and 52%). CONCLUSIONS: Several areas of end-of-life
      care provision could be improved. Early communication and exploration of wishes
      and appointment of proxy decision-makers are important components of an early
      palliative care approach which appears to be initiated too infrequently.

PMID- 22647227
TI  - [A woman with a chronic wound on the clavicle].
AB  - A 49-year-old woman, who was treated several times with radiotherapy for breast
      cancer, developed a chronic wound on her right clavicle.

PMID- 22647228
TI  - [Merkel cell carcinoma during treatment with TNF-alpha inhibitors: coincidence or
      warning?].
AB  - BACKGROUND: Increasing numbers of patients are being treated with TNF-alpha
      inhibitors. Two patients in our outpatient clinic developed Merkel cell carcinoma
      during treatment with TNF alpha inhibitors. Since this is a very rare malignancy,
      this is a remarkable observation. CASE DESCRIPTION: A 70-year-old male with
      rheumatoid arthritis had been treated with etanercept for two years when he
      discovered a nodule on his elbow that started growing rapidly. It was diagnosed
      as Merkel cell carcinoma. Despite treatment, the patient died 2 years later.
      CONCLUSION: Merkel cell carcinoma is an aggressive malignancy with a clinically
      benign aspect. Patients treated with TNF-alpha inhibitors possibly have an
      increased risk of developing this malignancy.

PMID- 22647229
TI  - [Chewing gum to prevent postoperative ileus].
AB  - Postoperative ileus is a commonly occurring complication after abdominal surgery.
      Reduced well-being and ileus related complications lead to extension of hospital
      stay. An early commencement of postoperative feeding to stimulate the digestive
      system is not always achievable in practice. Recent studies suggest that use of
      chewing gum can be effective in preventing postoperative ileus by a similar
      mechanism of action to early postoperative feeding. However, these studies were
      small in size and of varying quality. Recently the "Chewing gum study"
      ("Kauwgomstudie") to investigate the effect of general use of chewing gum after
      abdominal surgery has been started in the Netherlands.

PMID- 22647230
TI  - DHEA administration and exercise training improves insulin resistance in obese
      rats.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) is precursor of sex steroid hormone. We
      demonstrated that acute DHEA injection to type 1 diabetes model rats induced
      improvement of hyperglycemia. However, the effect of the combination of DHEA
      administration and exercise training on insulin resistance is still unclear. This
      study was undertaken to determine whether 6-weeks of DHEA administration and/or
      exercise training improve insulin resistance in obese male rats. METHODS: After
      14 weeks of a high-sucrose diet, obese male Wistar rats were assigned randomly to
      one of four groups: control, DHEA administration, exercise training, and a
      combination of DHEA administration and exercise training (n = 10 each group).
      RESULTS: After 6-weeks of DHEA administration and/or exercise training, rats in
      the combination group weighed significantly less and had lower serum insulin
      levels than rats in the other groups. Moreover, the rats treated with DHEA alone
      or DHEA and exercise had significantly lower fasting glucose levels (combination,
      84 +/- 6.5 mg/dL; DHEA, 102 +/- 9.5 mg/dL; control, 148 +/- 10.5 mg/dL). In
      addition, insulin sensitivity check index showed significant improvements in the
      combination group (combination, 0.347 +/- 0.11; exercise, 0.337 +/- 0.16%; DHEA,
      0.331 +/- 0.14; control, 0.308 +/- 0.12). Muscular DHEA and 5alpha
      dihydrotestosterone (DHT) concentrations were significantly higher in the
      combination group, and closely correlated with the quantitative insulin
      sensitivity check index (DHEA: r = 0.71, p < 0.01; DHT: r = 0.69, p < 0.01).
      CONCLUSION: These results showed that a combination of DHEA administration and
      exercise training effectively improved fasting blood glucose and insulin levels,
      and insulin sensitivity, which may reflect increased muscular DHEA and DHT
      concentrations.

PMID- 22647231
TI  - Improving carbon fixation pathways.
AB  - A recent resurgence in basic and applied research on photosynthesis has been
      driven in part by recognition that fulfilling future food and energy requirements
      will necessitate improvements in crop carbon-fixation efficiencies.
      Photosynthesis in traditional terrestrial crops is being reexamined in light of
      molecular strategies employed by photosynthetic microbes to enhance the activity
      of the Calvin cycle. Synthetic biology is well-situated to provide original
      approaches for compartmentalizing and enhancing photosynthetic reactions in a
      species independent manner. Furthermore, the elucidation of alternative carbon
      fixation routes distinct from the Calvin cycle raises possibilities that novel
      pathways and organisms can be utilized to fix atmospheric carbon dioxide into
      useful materials.

PMID- 22647232
TI  - Heavy metals and polycyclic aromatic hydrocarbons: pollution and ecological risk
      assessment in street dust of Tehran.
AB  - 50 street dust samples from four major streets in eastern and southern Tehran,
      the capital of Iran, were analyzed for metal pollution (Cu, Cr, Pb, Ni, Cd, Zn,
      Fe, Mn and Li). Hakanson's method was used to determine the Risk Index (RI) and
      ecological risks. Amongst these samples, 21 were also analyzed for polycyclic
      aromatic hydrocarbons (PAHs). Correlation, cluster and principal component
      analyses identified probable natural and anthropogenic sources of contaminants.
      The dust had elevated concentrations of Pb, Cd, Cu, Cr, Ni, Zn, Fe and PAHs.
      Enrichment factors of Cu, Pb, Cd and Zn showed that the dust is extremely
      enriched in these metals. Multivariate statistical analyses revealed that Cu, Pb,
      Zn, Fe and PAHs and, to a lesser extent, Cr and Ni have common anthropogenic
      sources. While Mn and Li were identified to have natural sources, Cd may have
      different anthropogenic origins. All samples demonstrated high ecological risk.
      Traffic and related activities, petrogenic and pyrogenic sources are likely to be
      the main anthropogenic sources of heavy metals and PAHs in Tehran dust.

PMID- 22647233
TI  - Arsenic remediation from drinking water by synthesized nano-alumina dispersed in
      chitosan-grafted polyacrylamide.
AB  - An arsenic adsorbent comprising alumina nanoparticles dispersed in polymer matrix
      was developed and its removal potential studied. Alumina nanoparticles were
      prepared by reverse microemulsion technique and these were immobilized on
      chitosan grafted polyacrylamide matrix by in situ dispersion. The loading
      capacity of this new synthesized adsorbent was found to be high (6.56 mg/g).
      Batch adsorption studies were performed as a function of contact time, initial
      arsenic concentration, pH and presence of competing anions. The removal was found
      to be pH dependent, and maximum removal was obtained at pH 7.2 while the
      equilibrium time was 6h. The equilibrium adsorption data fitted very well with
      Freundlich isotherm. However, the D-R isotherm studies indicated that
      chemisorptions might play an important role. This was also confirmed by the FTIR
      study of the arsenic loaded adsorbent. A mechanism of arsenic sorption by the new
      polymeric adsorbent has been proposed. The regeneration study of the adsorbent
      resulted in retention of 94% capacity in the fifth cycle. An optimum pH of 7.2,
      operation at normal temperature, high adsorption capacity and good recycle
      potential of this new adsorbent would make it an ideal material for removal of
      arsenic from drinking water.

PMID- 22647234
TI  - Removal of iopromide and degradation characteristics in electron beam irradiation
      process.
AB  - The aim of this study is to evaluate the removal efficiency of iopromide using
      electron beam (E-beam) irradiation technology, and its degradation
      characteristics with hydroxyl radical (OH) and hydrated electron (e(aq)(-)).
      Studies are conducted with different initial concentrations of iopromide in pure
      water and in the presence of hydrogen peroxide, bicarbonate ion, or sulfite ion.
      E-beam absorbed dose of 19.6 kGy was required to achieve 90% degradation of 100
      MUM iopromide and the E-beam/H(2)O(2) system increased the removal efficiency by
      an amount of OH. generation. In the presence of OH scavengers (10 mM sulfite
      ion), the required dose for 90% removal of 100 MUM iopromide was only 0.9 kGy.
      This greatly enhanced removal was achieved in the presence of OH. scavengers,
      which was rather unexpected and unlike the results obtained from most advanced
      oxidation process (AOP) experiments. The reasons for this enhancement can be
      explained by a kinetic study using the bimolecular rate constants of each
      reaction species. To explore the reaction scheme of iopromide with OH. or e(aq)(
      ) and the percent of mineralization for the two reaction paths, the total organic
      carbon (TOC), released iodide, and intermediates were analyzed.

PMID- 22647235
TI  - Squamous cell carcinoma of the oral cavity and the oropharynx in patients less
      than 40 years of age: a 20-year analysis.
AB  - BACKGROUND: Squamous cell carcinoma mainly afflicts patients older than 40 years
      of age however, few cases are seen in younger patients. The aim of this study
      therefore was to determine the incidence of squamous cell carcinoma of the oral
      cavity and oropharynx in patients less than 40 years of age with a view to
      assessing the prognosis over a period of time. METHODS: This was a 20 years
      retrospective review of patients who were histologically diagnosed with squamous
      cell carcinoma of the oral cavity and the oropharynx at the Department of Cranio
      Maxillo-Facial Surgery of the Hannover Medical School, Germany and had not
      received treatment anywhere else. Records of these patients were analysed for age
      and sex distribution, tumour staging and differentiation, location, treatment
      given, recurrences and metastasis, time between diagnosis and death or last
      contact with patient, and possible cause of death. Comparisons were also made
      with patients older than 40 years of age. RESULTS AND DISCUSSION: A total of 977
      patients treated for squamous cell carcinoma of the oral cavity and the
      oropharynx in the 20-year period of this study were included. Thirty eight (3.9
      %) of the overall patient population were under 40 years of age. Among these, 30
      (78.9%) were males and 8 (21.1%) were females. The incidence was highest in the
      30-39 year age group accounting for 31 (81.6%) of the 38 patients. The moderately
      differentiated carcinoma was commonest (24; 63.2%). The floor of the mouth had
      the highest number of tumours (15; 39.5%), but none was seen in the oropharynx.
      Surgery alone was the main stay of treatment given to 26 (68.4%) patients. At the
      end of the study period, 13 (34.2%) patients had died of the tumour and the 5
      year survival rate was 66.2%. In the older patient group (>40 years), 42.7% died
      from the tumour and the 5-year survival rate was 57.6%. CONCLUSION: The results
      from the present study showed that young adults may have a better prognosis
      especially in terms of long term overall survival from oral and oropharyngeal
      carcinoma.

PMID- 22647236
TI  - Expression of TRPV1 in cortical lesions from patients with tuberous sclerosis
      complex and focal cortical dysplasia type IIb.
AB  - Tuberous sclerosis complex (TSC) and focal cortical dysplasia type IIb (FCDIIb)
      are recognized as causes of intractable epilepsy. Transient receptor potential
      vanilloid receptor 1 (TRPV1), a member of the transient receptor potential
      family, is the capsaicin receptor and is known to be involved in peripheral
      nociception. Recent evidence suggested that TRPV1 may be a contributing factor in
      epileptogenicity. Here, we evaluated the expression of TRPV1 in the cortical
      lesions of TSC and FCDIIb relative to normal control cortex. TRPV1 was studied in
      epilepsy surgery cases with TSC (cortical tubers; n=12) and FCDIIb (n=12) using
      immunocytochemistry, confocal analysis, and Western blotting (WB).
      Immunohistochemical location of the TRPV1 was predominately detected in the
      abnormal cell types, such as dysmorphic neurons, balloon cells (BCs) and giant
      cells. Co-localization assays further revealed that cells expressing TRPV1 mainly
      had a neuronal lineage, apart from some BCs in FCDIIb, which obviously were of
      astrocytic lineage. The increased TRPV1 expression within the dysplastic cortex
      of TSC and FCDIIb was confirmed by WB. Interestingly, both immunohistochemical
      and WB data indicated that TRPV1 might have both cytoplasm and nuclear
      distribution, suggesting a potential nuclear role of TRPV1. The over-expression
      of TRPV1 in cortical lesions of TSC and FCDIIb suggested the possible involvement
      of TRPV1 in the intrinsic and increased epileptogenicity of malformations of
      cortical development associated epilepsy diseases and may represent a potential
      antiepileptogenic target. However, the current data are merely descriptive, and
      further electrophysiological investigation is needed in the future.

PMID- 22647237
TI  - Synthesis of silver nanoplates by two-dimensional oriented attachment.
AB  - Synthesis of silver nanoplates was studied in the modified polyol method, where
      the nucleation and seed stage occurred in a poly(ethylene glycol) (PEG)-water
      mixture solution, and the growth stage happened in the PEG environment. The
      morphological evolution of nanoplates was characterized using UV, SEM, and TEM.
      Interestingly, plane nanostructures with unusual jagged edges were finally formed
      in our modified polyol method. Using TEM, we observed the medium state of fusion
      between two nanoplates, resulting in generating unusual jagged edges. Therefore,
      a novel two-dimensional oriented attachment occurred in our modified polyol
      method, which involves smaller nanoplates as the building blocks. Further control
      experiments showed that the presence of water could break this kinetic preferred
      reactivity, leading to the formation of nanoparticles.

PMID- 22647238
TI  - High expression of p300 is linked to aggressive features and poor prognosis of
      nasopharyngeal carcinoma.
AB  - BACKGROUND: Increased expression of transcriptional coactivator p300 has been
      observed in a variety of human cancers. However, the expression status of p300
      protein/mRNA in nasopharyngeal carcinoma (NPC) tissues and its
      clinicopathologic/prognostic implication are poorly understood. METHODS: In our
      study, mRNA and protein expression levels of p300 was explored by reverse
      transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and
      immunohistochemistry (IHC) in nasopharyngeal mucosal and NPC tissues. The data
      were analyzed by receiver operating characteristic (ROC) curve analysis,
      spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards
      regression model. RESULTS: Up-regulated expression of p300 mRNA/p300 protein was
      detected in NPC tissues by RT-PCR and WB, when compared to nasopharyngeal mucosal
      tissues. Based on ROC curve analysis, the cutoff score for p300 high expression
      was defined when more than 35% of the tumor cells were positively stained. High
      expression of p300 was observed in 127/209 (60.7%) of NPCs. In NPCs, high
      expression of p300 was positively associated with later T classification, later N
      classification, distant metastasis and later clinical stage (P < 0.05). In
      univariate survival analysis, overexpression of p300 was found to be an indicator
      of progression-free (P = 0.002) and overall survival (P = 0.001) in NPCs. More
      importantly, p300 expression was evaluated as an independent prognostic factor
      for NPC in multivariate analysis (P = 0.036). CONCLUSIONS: Our findings support
      that high expression of p300 protein might be important in conferring a more
      aggressive behavior, and is an independent molecular marker for shortened
      survival time of patients with NPC.

PMID- 22647239
TI  - Inverse relationship between fat intake and blood lead levels in the Korean adult
      population in the KNHANES 2007-2009.
AB  - OBJECTIVES: Blood lead levels (BLLs) in the Korean adult population are about
      twofold higher than those in the US adult population, which may be related to
      nutrient intake. We examined which nutritional factors might be associated with
      decreased BLL. METHODS: This study was based on Korean National Health and
      Nutrition Examination Survey data obtained over 3 years (2007-2009) using a
      rolling sampling design involving a complex, stratified, multistage, probability
      cluster survey of a representative sample of the non-institutionalized civilian
      population of South Korea. RESULTS: A multiple regression analysis after
      controlling for covariates indicated that dietary fat and protein were
      significant opposite predictors of BLL in five different models; fat and protein
      intake had negative and positive associations with BLL, respectively. Covariates
      used in the analysis were sex, age, regional area, education level, smoking and
      drinking status, hypertension, use of antihypertensive drugs, diabetes, use of
      antidiabetic drugs, use of cholesterol-lowering drugs, hemoglobin level, and
      exposure to chemical substances during daily life. Intake levels of other
      nutrients, such as dietary fiber, carbohydrates, and calcium, did not show any
      significant effect on BLL. Gender was also an important predictor: BLL was
      significantly higher in men than women. However, total femur T-score, which
      represents bone mass, was unaffected by BLL. When calculating adjusted predicted
      marginal values of blood lead according to dietary fat percentage, BLL was lower
      by 5.3% and 8.0% in men when fat intake was increased from 10% to 20% and 25%,
      respectively. This effect of fat intake on BLL was minimal in women. CONCLUSION:
      The accumulation of body stores of lead from lead exposure may be reduced by
      increasing dietary fat consumption to 25% of energy intake, especially in men.
      However, this must be weighed against possible cardiovascular risks of higher fat
      diets.

PMID- 22647240
TI  - Solar photocatalytic treatment of trimethoprim in four environmental matrices at
      a pilot scale: transformation products and ecotoxicity evaluation.
AB  - The pilot-scale solar degradation of trimethoprim (TMP) in different water
      matrices (demineralized water: DW, simulated natural freshwater: SW; simulated
      wastewater: SWW; and real effluent: RE) was investigated in this study. DOC
      removal was lower in the case of SW compared to DW, which can be attributed to
      the presence of inorganic anions which may act as scavengers of the HO..
      Furthermore, the presence of organic carbon and higher salt content in SWW and RE
      led to lower mineralization per dose of hydrogen peroxide compared to DW and SW.
      Toxicity assays in SWW and RE were also performed indicating that toxicity is
      attributed to the compounds present in RE and their by-products formed during
      solar Fenton treatment and not to the intermediates formed by the oxidation of
      TMP. A large number of compounds generated by the photocatalytic transformation
      of TMP were identified by UPLC-QToF/MS. The degradation pathway revealed
      differences among the four matrices; however hydroxylation, demethylation and
      cleavage reactions were observed in all matrices. To the best of our knowledge
      this is the first time that TMP degradation products have been identified by
      adopting a solar Fenton process at a pilot-scale set-up, using four different
      aqueous matrices.

PMID- 22647241
TI  - Comparison of interannual removal variation of various constructed wetland types.
AB  - Seven mesocosm-scale (1m(2)) constructed wetlands (CWs) of different
      configurations were operated outdoors for thirty-nine months under the same
      conditions to assess their ability to remove organic matter and nutrients from
      urban wastewaters. CWs differed in some design parameters, namely the presence of
      plants, the species chosen (i.e., Typha angustifolia or Phragmites australis),
      the flow configuration (i.e., surface flow or subsurface flow) and the
      presence/absence of a gravel bed. It was observed that, in general, removal
      efficiencies decreased with the aging of the system and that seasonality had a
      great influence on CWs. A comparison was made in order to figure out which kind
      of CW was more efficient for the removal of every pollutant in the long term.
      Planted systems were clearly better than unplanted systems even in winter.
      Efficiency differences among CWs were not extremely great, especially after a few
      years. However, some types of CWs were more adequate for the removal of certain
      pollutants. The effect of the aging on the main parameters involved in pollutant
      removal in CWs (temperature, pH, conductivity, dissolved oxygen concentration and
      redox potential) was assessed. The efficiency of CWs should not be evaluated
      based on short monitoring periods (1-2 years) after the start-up of the systems,
      but on longer periods.

PMID- 22647242
TI  - Short-term effects of ambient air pollution on stroke: who is most vulnerable?
AB  - Several studies have demonstrated positive associations between day-to-day
      increases in air pollution and stroke. These findings have been inconsistent, and
      the influence of patient characteristics has been largely ignored. In this study,
      we investigated the short-term effects of air pollution on stroke using a time
      stratified case-crossover design. Data for hospital visits for stroke were
      extracted from 5927 medical charts of patients who presented to emergency
      departments between 2003 and 2009 in Edmonton, Canada. Daily concentrations of
      five air pollutants (NO(2), PM (2.5), CO, O(3), and SO(2)) were obtained from
      fixed-site monitors. Relative humidity and temperature were obtained from a
      metrological station operating at the city's airport. Chart data included:
      disease history, medication use, and smoking status. Conditional logistic
      regression was used to estimate the odds ratio (OR) of stroke in relation to an
      increase in the interquartile range for each pollutant. Positive associations
      were observed between ischemic stroke and air pollution during the 'warm' season
      (April through September). Specifically, the OR for an increase in 9.4 ppb in the
      3-day average of NO(2) was 1.50 (95% CI: 1.12, 2.01). There were no statistically
      significant associations with any of the other pollutants after adjusting for
      NO(2) concentrations. Associations with ischemic stroke were stronger for those
      with a history of stroke (OR=2.31; 95% CI: 1.39, 3.83), heart disease (OR=1.99;
      95% CI: 1.20, 3.28), and taking medication for diabetes (OR=2.03; 95% CI: 1.14,
      3.59). Temperature was inversely associated with ischemic stroke during the
      'warm' season, but no associations were evident with the other stroke subtypes.
      Air pollution was not associated with hemorrhagic stroke or transient ischemic
      attacks. The findings suggest that specific patient characteristics modify
      associations between air pollution and ischemic stroke.

PMID- 22647243
TI  - A yearly spraying of olive mill wastewater on agricultural soil over six
      successive years: impact of different application rates on olive production,
      phenolic compounds, phytotoxicity and microbial counts.
AB  - Olive mill wastewater (OMW) spraying effects onto olive-tree fields were
      investigated. Three OMW levels (50, 100 and 200 m(3)ha(-1)year(-1)) were applied
      over six successive years. Olive-crop yields, phenolic compounds progress,
      phytotoxicity and microbial counts were studied at different soil depths. Olive
      yield showed improvements with OMW level applied. Soil polyphenolic content
      increased progressively in relation to OMW levels in all the investigated layers.
      However, no significant difference was noted in lowest treatment rate compared to
      the control field. In the soil upper-layers (0-40 cm), five phenolic compounds
      were identified over six consecutive years of OMW-spraying. In all the soil
      layers, the radish germination index exceeded 85%. However, tomato germination
      test values decreased with the applied OMW amount. For all treatments, microbial
      counts increased with OMW quantities and spraying frequency. Matrix correlation
      showed a strong relationship between soil polyphenol content and microorganisms,
      and a negative one to tomato germination index.

PMID- 22647244
TI  - Identifying targets of multiple co-regulating transcription factors from
      expression time-series by Bayesian model comparison.
AB  - BACKGROUND: Complete transcriptional regulatory network inference is a huge
      challenge because of the complexity of the network and sparsity of available
      data. One approach to make it more manageable is to focus on the inference of
      context-specific networks involving a few interacting transcription factors (TFs)
      and all of their target genes. RESULTS: We present a computational framework for
      Bayesian statistical inference of target genes of multiple interacting TFs from
      high-throughput gene expression time-series data. We use ordinary differential
      equation models that describe transcription of target genes taking into account
      combinatorial regulation. The method consists of a training and a prediction
      phase. During the training phase we infer the unobserved TF protein
      concentrations on a subnetwork of approximately known regulatory structure.
      During the prediction phase we apply Bayesian model selection on a genome-wide
      scale and score all alternative regulatory structures for each target gene. We
      use our methodology to identify targets of five TFs regulating Drosophila
      melanogaster mesoderm development. We find that confident predicted links between
      TFs and targets are significantly enriched for supporting ChIP-chip binding
      events and annotated TF-gene interations. Our method statistically significantly
      outperforms existing alternatives. CONCLUSIONS: Our results show that it is
      possible to infer regulatory links between multiple interacting TFs and their
      target genes even from a single relatively short time series and in presence of
      unmodelled confounders and unreliable prior knowledge on training network
      connectivity. Introducing data from several different experimental perturbations
      significantly increases the accuracy.

PMID- 22647245
TI  - Additional weight influences the reaching behavior of low-risk preterm infants.
AB  - The authors investigated the influence of additional weight in the reaching
      behavior of preterm infants. Nine low-risk preterm and 10 full-term infants age 5
      7 months participated. A toy was presented in two procedures: (a) baseline and
      (b) additional weight (bracelet with weight of 20% of the infant's upper limb
      mass). The additional weight reduced the straightness index at 5 months,
      increased the mean velocity and decreased the movement units at all months, and
      increased unsuccessful grasps at 5 and 7 months in preterm infants. Preterm
      infants showed less movement units at all months and less unsuccessful grasps at
      6 months compared with full-term infants. Weight disturbance seems to change the
      intrinsic dynamics involved in reaching movements of 5-7-month-old preterm
      infants.

PMID- 22647246
TI  - Kinematic motion analysis and muscle activation patterns of continuous reaching
      in survivors of stroke.
AB  - Coordinated reaching requires continuous interaction between the efferent motor
      output and afferent feedback; this interaction may be significantly compromised
      following a stroke. The authors sought to characterize how survivors of stroke
      generate continuous, goal-directed reaching. Sixteen survivors of stroke
      completed functional testing of the stroke-affected side and a continuous
      reaching task between 2 targets with both sides. Motion analysis and
      electromyography data were collected to determine segmental contributions to
      reach (e.g., amount of compensatory trunk), spatiotemporal parameters (e.g., peak
      velocities), and muscle activation patterns (MAP). Repeated measures analyses of
      variance compared how survivors of stroke reach with the stroke-affected versus
      less affected sides. Correlations were determined between kinematic outcomes and
      functional ability. Participants used significantly more trunk movement and less
      shoulder flexion and elbow extension when reaching with the stroke-affected side.
      This corresponded with less muscle activity in the proximal musculature including
      the anterior, middle, and posterior deltoid on the stroke-affected side. There
      were significant correlations between the segmental contributions to reach,
      functional ability, and MAPs. Survivors of stroke generate reduced MAPs in the
      stroke-affected side corresponding to altered segmental kinematics and function
      ability. These findings suggest that impairments in the ability to generate
      sufficient MAPs may contribute to the difficulty in generating continuous
      reaching motions.

PMID- 22647247
TI  - A randomised study on the effects of fish protein supplement on glucose
      tolerance, lipids and body composition in overweight adults.
AB  - The popularity of high-protein diets for weight reduction is immense. However,
      the potential benefits from altering the source of dietary protein rather than
      the amount is scarcely investigated. In the present study, we examined the
      effects of fish protein supplement on glucose and lipid metabolism in overweight
      adults. A total of thirty-four overweight adults were randomised to 8 weeks'
      supplementation with fish protein or placebo tablets (controls). The intake of
      fish protein supplement was 3 g/d for the first 4 weeks and 6 g/d for the last 4
      weeks. In this study, 8 weeks of fish protein supplementation resulted in lower
      values of fasting glucose (P< 0.05), 2 h postprandial glucose (P< 0.05) and
      glucose-area under the curve (AUC) (five measurements over 2 h, P< 0.05) after
      fish protein supplementation compared to controls. Glucose-AUC was decreased
      after 8 weeks with fish protein supplement compared to baseline (P< 0.05),
      concomitant with increased 30 min and decreased 90 min and 2 h insulin C-peptide
      level (P< 0.05), and reduced LDL-cholesterol (P< 0.05). Body muscle % was
      increased (P< 0.05) and body fat % was reduced (P< 0.05) after 4 weeks'
      supplementation. Physical activity and energy and macronutrients intake did not
      change during the course of the study. In conclusion, short-term daily
      supplementation with a low dose of fish protein may have beneficial effects on
      blood levels of glucose and LDL-cholesterol as well as glucose tolerance and body
      composition in overweight adults. The long-term effects of fish protein
      supplementation is of interest in the context of using more fish as a protein
      source in the diet, and the effects of inclusion of fish in the diet of
      individuals with low glucose tolerance should be evaluated.

PMID- 22647248
TI  - Why do patients and their families not use services for dementia? Perspectives
      from a developed Asian country.
AB  - BACKGROUND: Despite the need for community services to support the intensive
      levels of care provided by dementia family caregivers, findings consistently
      indicate low rates of service utilization. This study aims to explore the extent
      of service use and examine the factors that may influence the use of services in
      a sample of family caregivers of Persons With Dementia (PWD). METHODS: Two
      hundred and seventy-two family caregivers completed a questionnaire assessing
      caregiver burden, knowledge and use of services, dementia severity, frequency of
      problem behaviors and socio-demographic characteristics. RESULTS: The rate of
      service use was modest with 39.9% using any of the available services. Reasons
      for non-use included lack of time (26.2%), perceived lack of need (18.5%), and
      presence of domestic help (21%). Separate regression models were evaluated to
      identify factors associated with caregiver service use and PWD service-use.
      Caregiver employment status (OR = 0.53, CI = 0.30-0.94) and knowledge of
      available services (OR = 4.22, CI = 2.23-7.98) contributed significantly to the
      model distinguishing caregiver service users from non-users. Knowledge of
      available services (OR = 2.14, CI = 1.23-3.71) was the only significant predictor
      of service use targeted at the PWD. CONCLUSIONS: Given that knowledge
      significantly increased the odds of service use, strategies should be designed to
      raise awareness about the availability of dementia support services in the
      community and provide a deeper understanding about the value of such services.
      Future research should employ larger sample sizes and explore factors not
      measured in this study that might potentially better explain use of services.

PMID- 22647249
TI  - The insulinogenic effect of whey protein is partially mediated by a direct effect
      of amino acids and GIP on beta-cells.
AB  - BACKGROUND: Whey protein increases postprandial serum insulin levels. This has
      been associated with increased serum levels of leucine, isoleucine, valine,
      lysine, threonine and the incretin hormone glucose-dependent insulinotropic
      polypeptide (GIP). We have examined the effects of these putative mediators of
      whey's action on insulin secretion from isolated mouse Langerhans islets.
      METHODS: Mouse pancreatic islets were incubated with serum drawn from healthy
      individuals after ingestion of carbohydrate equivalent meals of whey protein
      (whey serum), or white wheat bread (control serum). In addition the effect of
      individual amino acid combinations on insulin secretion was also tested.
      Furthermore, the stimulatory effects of whey serum on insulin secretion was
      tested in vitro in the absence and presence of a GIP receptor antagonist
      ((Pro(3))GIP[mPEG]). RESULTS: Postprandial amino acids, glucose-dependent
      insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) responses
      were higher after whey compared to white wheat bread. A stimulatory effect on
      insulin release from isolated islets was observed with serum after whey obtained
      at 15 min (+87%, P < 0.05) and 30 min (+139%, P < 0.05) postprandially, compared
      with control serum. The combination of isoleucine, leucine, valine, lysine and
      threonine exerted strong stimulatory effect on insulin secretion (+270%, P <
      0.05), which was further augmented by GIP (+558% compared to that produced by
      glucose, P < 0.05). The stimulatory action of whey on insulin secretion was
      reduced by the GIP-receptor antagonist (Pro(3))GIP[mPEG]) at both 15 and 30 min (
      56% and -59%, P < 0.05). CONCLUSIONS: Compared with white wheat bread meal, whey
      causes an increase of postprandial insulin, plasma amino acids, GIP and GLP-1
      responses. The in vitro data suggest that whey protein exerts its insulinogenic
      effect by preferential elevation of the plasma concentrations of certain amino
      acids, GIP and GLP-1.

PMID- 22647250
TI  - Reducing ligation bias of small RNAs in libraries for next generation sequencing.
AB  - BACKGROUND: The use of nucleic acid-modifying enzymes has driven the rapid
      advancement in molecular biology. Understanding their function is important for
      modifying or improving their activity. However, functional analysis usually
      relies upon low-throughput experiments. Here we present a method for functional
      analysis of nucleic acid-modifying enzymes using next generation sequencing.
      FINDINGS: We demonstrate that sequencing data of libraries generated by RNA
      ligases can reveal novel secondary structure preferences of these enzymes, which
      are used in small RNA cloning and library preparation for NGS. Using this
      knowledge we demonstrate that the cloning bias in small RNA libraries is RNA
      ligase-dependent. We developed a high definition (HD) protocol that reduces the
      RNA ligase-dependent cloning bias. The HD protocol doubled read coverage, is
      quantitative and found previously unidentified microRNAs. In addition, we show
      that microRNAs in miRBase are those preferred by the adapters of the main
      sequencing platform. CONCLUSIONS: Sequencing bias of small RNAs partially
      influenced which microRNAs have been studied in depth; therefore most previous
      small RNA profiling experiments should be re-evaluated. New microRNAs are likely
      to be found, which were selected against by existing adapters. Preference of
      currently used adapters towards known microRNAs suggests that the annotation of
      all existing small RNAs, including miRNAs, siRNAs and piRNAs, has been biased.

PMID- 22647252
TI  - Biological activities and volatile constituents of Daucus muricatus L. from
      Algeria.
AB  - BACKGROUND: In order to find new bioactive natural products, the antimicrobial
      and antioxidant activities of essential oil components extracted from the
      separated organs of the Algerian medicinal and aromatic plant Daucus muricatus L.
      were studied. RESULTS: The chemical composition of essential oils obtained by
      hydrodistillation (HD) was investigated using Gas Chromatography-Retention
      Indices (GC-RI) and GC-Mass Spectrometry (GC-MS). Two types of essential oils
      were produced by D. muricatus: (i) The oil from roots is mainly composed by
      nonterpenic oxygenated compounds (59.8 g/100 g), and (ii) the aerial part oils
      (i.e., the leaves, stems, flowers, and umbels) was mainly composed by terpenic
      hydrocarbon compounds (62.3-72.2 g/100 g). The chemical composition of the
      volatile fraction isolated from different organs of Daucus muricatus were studied
      by HS-SPME/GC-RI and GC-MS after optimization of Solid Phase MicroExtraction
      parameters. For all organs studied, the main volatiles emitted by the plant were
      hydrocarbon compounds (60.7-82.2 g/100 g). Only quantitative differences between
      the volatiles of the separated organs studied were observed. In addition, the
      activity of the oil of D. muricatus against eight bacterial strains and one yeast
      was investigated. The oil from roots revealed active against S. aureus, while the
      essential oil obtained from the aerial parts was active against the yeast C.
      albicans. CONCLUSIONS: Daucus muricatus essential oil seems be a promising source
      of natural products with potential antimicrobial activity.

PMID- 22647251
TI  - Routine physical activity and mortality in Mexican Americans aged 75 and older.
AB  - OBJECTIVES: To examine the association between routine physical activity and risk
      of 3-year mortality in Mexican Americans aged 75 and older. DESIGN: Longitudinal
      study involving a population-based survey. SETTING: Hispanic Established
      Population for the Epidemiologic Study of the Elderly (H-EPESE) survey conducted
      in the southwestern United States (TX, CO, AZ, NM, CA). PARTICIPANTS: Mexican
      American men and women aged 75 and older (N = 948) participating in the H-EPESE.
      MEASUREMENTS: Responses to the Physical Activity Scale for the Elderly (PASE)
      were assessed in 2005-06. Mortality was determined according to report of
      relatives at 3-year follow-up and from the National Death Index. Covariates
      included sociodemographic characteristics, financial strain, smoking status, body
      mass index, activities of daily living, depressive symptoms, cognitive function,
      and comorbid conditions. RESULTS: The mean age of the sample was 82.2 +/- 4.5.
      Cox proportional hazard regression estimated that the hazard ratios of death for
      persons in the low, moderate, and high quartiles of physical activity (PASE
      scale) ranged from 0.36 (95% confidence interval (CI) = 0.21-0.62) to 0.50 (95%
      CI = 0.31-0.82) compared to persons in the sedentary quartile after adjusting for
      covariates. CONCLUSION: Routine physical activity involving household and leisure
      activities was associated with lower 3-year risk of mortality in a sample of
      older Mexican Americans living in the community.

PMID- 22647253
TI  - Anomalous luminescence phenomena of indium-doped ZnO nanostructures grown on Si
      substrates by the hydrothermal method.
AB  - In recent years, zinc oxide (ZnO) has become one of the most popular research
      materials due to its unique properties and various applications. ZnO is an
      intrinsic semiconductor, with a wide bandgap (3.37 eV) and large exciton binding
      energy (60 meV) making it suitable for many optical applications. In this
      experiment, the simple hydrothermal method is used to grow indium-doped ZnO
      nanostructures on a silicon wafer, which are then annealed at different
      temperatures (400 degrees C to 1,000 degrees C) in an abundant oxygen atmosphere.
      This study discusses the surface structure and optical characteristic of ZnO
      nanomaterials. The structure of the ZnO nanostructures is analyzed by X-ray
      diffraction, the superficial state by scanning electron microscopy, and the
      optical measurements which are carried out using the temperature-dependent
      photoluminescence (PL) spectra. In this study, we discuss the broad peak energy
      of the yellow-orange emission which shows tendency towards a blueshift with the
      temperature increase in the PL spectra. This differs from other common
      semiconductors which have an increase in their peak energy of deep-level emission
      along with measurement temperature.

PMID- 22647254
TI  - Impaired LTP- but not LTD-like cortical plasticity in Alzheimer's disease
      patients.
AB  - In animal models of Alzheimer's disease (AD), amyloid-beta fragments interfere
      with mechanisms of cortical plasticity such as long-term potentiation (LTP) and
      long-term depression (LTD). In the current study, we applied repetitive
      transcranial magnetic stimulation over the primary motor cortex (M1) in AD
      patients and in age-matched healthy controls, using protocols of theta burst
      stimulation (TBS) that are known to induce plastic changes resembling the LTP and
      LTD mechanisms described in animal models. AD patients showed consistent LTD-like
      effects that were comparable to those obtained in healthy controls when submitted
      to 40 seconds of continuous TBS. Conversely, AD patients did not show any LTP
      like after effect when submitted to two different TBS protocols that induced an
      LTP-like effect in healthy controls such as intermittent TBS and 20 seconds of
      continuous TBS followed by one minute of muscular contraction. These results
      demonstrate the impairment of LTP-like together with normal LTD-like cortical
      plasticity in AD patients.

PMID- 22647255
TI  - Midlife rheumatoid arthritis increases the risk of cognitive impairment two
      decades later: a population-based study.
AB  - Inflammation has been associated with Alzheimer's disease (AD) and dementia. The
      association between rheumatoid arthritis (RA) or arthritis and dementia/AD has
      been investigated in several case-control or hospital- and register-based studies
      with mixed results. This long-term population-based study investigates the
      association between presence of joint disorders (RA and other joint disorders) in
      midlife and cognitive status later in life. 1,449 participants were first
      evaluated in 1972, 1977, 1982, and 1987 and follow-up was performed after 21
      years. A self-administered questionnaire including questions on joint disorders
      was used at both evaluations. Cognitive status (control, mild cognitive
      impairment, dementia/AD) was assessed at follow-up. The presence of any joint
      disorder in midlife was significantly associated with a worse cognitive status
      later in life: OR (95% CI) in an ordinal logistic regression analysis adjusted
      for age, gender, follow-up time, education, APOEepsilon4, body mass index,
      smoking, drug treatment, and diabetes was 1.96 (1.17-3.28). For RA only, OR (95%
      CI) was 2.77 (1.26-6.10). The correlation remained significant for RA when AD was
      considered instead of dementia OR (95% CI) 2.49 (1.09-5.67). The presence of
      joint disorders, especially RA, at midlife seems to be associated with a worse
      cognitive status later in life. Given the chronic inflammatory component of RA,
      this study suggests that inflammatory mechanisms may have an important role in
      increasing the risk of cognitive impairment and dementia/AD.

PMID- 22647256
TI  - Independent deficits of visual word and motion processing in aging and early
      Alzheimer's disease.
AB  - We tested whether visual processing impairments in aging and Alzheimer's disease
      (AD) reflect uniform posterior cortical decline, or independent disorders of
      visual processing for reading and navigation. Young and older normal controls
      were compared to early AD patients using psychophysical measures of visual word
      and motion processing. We find elevated perceptual thresholds for letters and
      word discrimination from young normal controls, to older normal controls, to
      early AD patients. Across subject groups, visual motion processing showed a
      similar pattern of increasing thresholds, with the greatest impact on radial
      pattern motion perception. Combined analyses show that letter, word, and motion
      processing impairments are independent of each other. Aging and AD may be
      accompanied by independent impairments of visual processing for reading and
      navigation. This suggests separate underlying disorders and highlights the need
      for comprehensive evaluations to detect early deficits.

PMID- 22647257
TI  - Serum progranulin levels in patients with frontotemporal lobar degeneration and
      Alzheimer's disease: detection of GRN mutations in a Spanish cohort.
AB  - Progranulin gene (GRN) mutations cause frontotemporal lobar degeneration (FTLD)
      with TDP43-positive inclusions, although its clinical phenotype is heterogeneous
      and includes patients classified as behavioral variant-FTLD (bvFTLD), progressive
      non-fluent aphasia (PNFA), corticobasal syndrome, Alzheimer's disease (AD), or
      Parkinson's disease (PD). Our main objective was to study if low serum
      progranulin protein (PGRN) levels may detect GRN mutations in a Spanish cohort of
      patients with FTLD or AD. Serum PGRN levels were measured in 112 subjects: 17
      bvFTLD, 20 PNFA, 4 semantic dementia, 34 sporadic AD, 9 AD-PSEN1 mutation
      carriers, 10 presymptomatic-PSEN1 mutation carriers, and 18 control individuals.
      We detected 5 patients with PGRN levels below 94 ng/mL: two of them had a
      clinical diagnosis of bvFTLD, two of PNFA, and one of AD. The screening for GRN
      mutations detected two probable pathogenic mutations (p.C366fsX1 and a new
      mutation: p.V279GfsX5) in three patients and one mutation of unclear pathogenic
      nature (p.C139R) in one patient. The other patient showed a normal GRN sequence
      but carried a PRNP gene mutation. We observed no differences in serum PGRN levels
      between controls (mean = 145.5 ng/mL, SD = 28.5) and the other neurodegenerative
      diseases, except for the carriers of pathological GRN gene mutations (mean = 50.5
      ng/mL, SD = 21.2). Null GRN mutation carriers also showed lower serum PGRN levels
      than the patient who was a carrier of p.C139R (92.3 ng/mL) and the one who was a
      carrier of the PRNP mutation (76.9 ng/mL). In conclusion, we detected GRN null
      mutations in patients with severely reduced serum PGRN levels, but not in
      patients with slightly reduced PGRN levels.

PMID- 22647258
TI  - Physical activity in middle-age and dementia in later life: findings from a
      prospective cohort of men in Caerphilly, South Wales and a meta-analysis.
AB  - Previous studies suggest that physical activity may be protective for dementia
      and cognitive impairment. We report findings comparing leisure-time and work
      related physical activity from the Caerphilly Prospective study (CaPS) with
      dementia and cognitive impairment not dementia (CIND) after around 16 years of
      follow-up. We synthesized our results with a meta-analysis specifically testing
      if length of follow-up was associated with the size of any association. Age
      adjusted models found no real association with dementia, and if anything
      increased risk for CIND (odds ratio (OR) highest versus lowest tertile 2.61, 95%
      CI 1.58 to 4.31), though this was attenuated after adjustment for other
      confounders (OR highest versus lowest tertile 1.38, 95% CI 0.78 to 2.44). There
      was no evidence that this differed by type (vascular versus non-vascular) of
      cognitive disease. Meta-analysis of other published effect estimates showed a
      protective effect of physical activity on cognitive impairment (OR 0.66, 95% CI
      0.52 to 0.85) but with significant heterogeneity which was partially explained by
      length of follow up (p = 0.03). A protective association was also seen for
      dementia (OR 0.78, 95% CI 0.65, 0.94), which did not appear to be related to
      follow-up length but there was evidence of small study bias (p = 0.002)
      suggesting an absence of small null studies. The apparent protective effects of
      physical activity on cognitive health may partially reflect reverse causation and
      current estimates may be overly optimistic in terms of cognitive benefits.

PMID- 22647259
TI  - Additive microglia-mediated neuronal injury caused by amyloid-beta and bacterial
      TLR agonists in murine neuron-microglia co-cultures quantified by an automated
      image analysis using cognition network technology.
AB  - Activated microglia is considered to be involved in the progression of
      Alzheimer's disease (AD). We investigated the effect of amyloid-beta(1-40)
      (Abeta(40) and exogenous agonists of Toll-like receptor (TLR) 1/2 (Pam(3)CSK(4))
      and TLR4 (LPS) on neurons in primary murine neuron-microglia co-cultures.
      Neuronal viability, assessed by quantifying the number of intact neuronal
      extensions and their crossings using a newly developed Definiens Cognition
      Network Technology-based method, was significantly decreased after treatment with
      Pam(3)CSK(4), LPS, and Abeta(40). Combined treatment with Abeta(40) and
      Pam(3)CSK(4) or LPS had an additive effect. Hence, in patients with AD,
      synergistic microglial activation by Abeta and bacterial products during
      infections might contribute to disease progression.

PMID- 22647260
TI  - Astrocytic adenosine A2A receptors control the amyloid-beta peptide-induced
      decrease of glutamate uptake.
AB  - Alzheimer's disease (AD) is characterized by a progressive cognitive impairment
      tightly correlated with the accumulation of amyloid-beta (Abeta) peptides (mainly
      Abeta(1-42)). There is a precocious disruption of glutamatergic synapses in AD,
      in line with an ability of Abeta to decrease astrocytic glutamate uptake.
      Accumulating evidence indicates that caffeine prevents the burden of AD, likely
      through the antagonism of A(2A) receptors (A(2A)R) which attenuates Abeta-induced
      memory impairment and synaptotoxicity. Since A(2A)R also modulate astrocytic
      glutamate uptake, we now tested if A(2A)R blockade could prevent the decrease of
      astrocytic glutamate uptake caused by Abeta. In cultured astrocytes, Abeta(1-42).
      (1 MUM for 24 hours) triggered an astrogliosis typified by an increased density
      of GFAP, which was mimicked by the A(2A)R agonist, CGS 26180 (30 nM), and
      prevented by the A(2A)R antagonist, SCH 58261 (100 nM). Abeta1-42 also decreased
      D-aspartate uptake by 28 +/- 4%, an effect abrogated upon genetic inactivation or
      pharmacological blockade of A(2A)R. In accordance with the long term control of
      glutamate transporter expression by A(2A)R, Abeta(1-42). enhanced the expression
      and density of astrocytic A(2A)R and decreased GLAST and GLT-I expression in
      astrocytes from wild type, but not from A(2A)R knockout mice. This impact of
      Abeta(1-42). on glutamate transporters and uptake, dependent on A(2A)R function,
      was also confirmed in an ex vivo astrocyte preparation (gliosomes) from rats
      intracerebroventricularly (icv) injected with Abeta(1-42). . These results
      provide the first demonstration for a direct key role of astrocytic A(2A)R in the
      ability of Abeta-induced impairment of glutamate uptake, which may underlie
      glutamatergic synaptic dysfunction and excitotoxicity in AD.

PMID- 22647261
TI  - Selected findings from the Religious Orders Study and Rush Memory and Aging
      Project.
AB  - The Religious Orders Study and the Rush Memory and Aging Project are both cohort
      studies of aging and dementia that include organ donation at death. Together,
      more than 2,700 persons have agreed to annual clinical evaluation and brain
      donation at death. A subset of participants also participated in a substudy that
      included ante-mortem imaging. We highlight recent findings that have been highly
      cited over the past five years. The findings fall into three general categories.
      The first relates to the neuropathology of probable Alzheimer's disease, mild
      cognitive impairment, and those without dementia or mild cognitive impairment.
      The second relates to risk factors for Alzheimer's disease and neuropathology.
      The third are clinical and imaging studies of mild cognitive impairment. The
      findings illustrate the range of insights that can be gained into cognitive aging
      by incorporating neuropathologic indices into well designed, prospective cohort
      studies.

PMID- 22647263
TI  - Imaging the onset and progression of Alzheimer's disease: implications for
      prevention trials.
AB  - Excess neuronal loss--atrophy--is an inevitable feature of Alzheimer's disease
      (AD). Following studies in the early 1990 s demonstrating that non-invasive
      imaging can be used to visualize excess volume loss, i.e., the consequences of
      atrophy in AD, a major interest has been improving and validating methods to
      quantify measures of atrophy from serially acquired magnetic resonance imaging.
      Here we summarize our experience of measuring the extent and pattern of atrophy
      to understand disease pathogenesis, particularly through studies of individuals
      with or destined to develop familial AD; to aid diagnosis; and as an outcome
      measure for treatment trials. As the field moves toward earlier diagnosis and
      prevention, we outline the important roles that we believe structural imaging
      will play alongside other biomarkers both in identifying individuals in the
      earliest stages of neurodegeneration and assessing the effects of novel
      therapies.

PMID- 22647262
TI  - Structural brain atlases: design, rationale, and applications in normal and
      pathological cohorts.
AB  - Structural magnetic resonance imaging (MRI) provides anatomical information about
      the brain in healthy as well as in diseased conditions. On the other hand,
      functional MRI (fMRI) provides information on the brain activity during
      performance of a specific task. Analysis of fMRI data requires the registration
      of the data to a reference brain template in order to identify the activated
      brain regions. Brain templates also find application in other neuroimaging
      modalities, such as diffusion tensor imaging and multi-voxel spectroscopy.
      Further, there are certain differences (e.g., brain shape and size) in the brains
      of populations of different origin and during diseased conditions like in
      Alzheimer's disease (AD), population and disease-specific brain templates may be
      considered crucial for accurate registration and subsequent analysis of fMRI as
      well as other neuroimaging data. This manuscript provides a comprehensive review
      of the history, construction and application of brain atlases. A chronological
      outline of the development of brain template design, starting from the Talairach
      and Tournoux atlas to the Chinese brain template (to date), along with their
      respective detailed construction protocols provides the backdrop to this
      manuscript. The manuscript also provides the automated workflow-based protocol
      for designing a population-specific brain atlas from structural MRI data using
      LONI Pipeline graphical workflow environment. We conclude by discussing the scope
      of brain templates as a research tool and their application in various
      neuroimaging modalities.

PMID- 22647264
TI  - From molecule to clinic and community for neurodegeneration: research to bridge
      translational gaps.
AB  - Six papers based on studies with particular epidemiological designs are presented
      here which have been selected on the basis of their visibility in the literature.
      The designs are intended to provide robust evidence on risk, natural history, and
      underpinning neurobiology and outcomes relevant to aging populations. There is a
      large case control study (the Late Onset Alzheimer's Disease study), a case
      cohort study of Parkinson's Disease (the CamPaIGN study), and the Medical
      Research Council Cognitive Function and Ageing Study. Each study has included
      genetic investigation and risk, and the latter two include investigation of the
      clinical syndromes and their natural histories in relation to underlying
      pathology. Each aimed to provide results which were as generalizable to usual
      older populations as possible and each has produced findings which have
      contributed to current understanding of genetic risk, the heterogeneity of the
      syndrome of Parkinson's disease, and the underlying neuropathology of dementia in
      older population. They have influenced thinking about future directions, and the
      cohorts on which the findings are based will continue to provide an important
      resource for novel areas of research and future health care planning.

PMID- 22647265
TI  - Reduction of dietary glycaemic load modifies the expression of microRNA
      potentially associated with energy balance and cancer pathways in pre-menopausal
      women.
AB  - Energy metabolism, insulin resistance and adiposity have been implicated in
      breast cancer, but dietary interventions to reduce breast cancer morbidity and
      mortality have had limited success. MicroRNA (miRNA) are short, non-coding RNA
      that participate in the control of metabolic processes through the post
      transcriptional modification of RNA. We investigated the effect of a low
      glycaemic load dietary intervention on miRNA expression, with subsequent
      bioinformatics pathway analyses to explore metabolic pathways potentially
      affected by the diet. Total RNA, including miRNA, was isolated from the serum of
      fourteen otherwise healthy pre-menopausal women with a high breast cancer risk
      participating in a 12-month dietary intervention designed to lower glycaemic load
      by at least 15% from baseline. Genome-wide miRNA expression was conducted using
      Illumina BeadChips. In the intervention subjects, three differentially expressed
      miRNA were validated by real-time (RT)-PCR, and in the twenty control
      participants, four top differentially expressed miRNA were evaluated to confirm a
      diet effect. In post-intervention v. baseline serum, twenty miRNA were found to
      be differentially expressed, with twelve up-regulated and eight down-regulated.
      These differentially expressed miRNA were predicted to be potentially associated
      with energy balance and cancer pathways based on exploratory enrichment analysis.
      Quantitative RT-PCR validations in the controls confirmed that the observed miRNA
      differential expression was dietary intervention induced. Manipulation of dietary
      glycaemic load has the potential to modify the expression of multiple miRNA
      predicted to be involved in energy balance and cancer pathways. Further research
      is necessary to confirm the role of these miRNA in the control of energy
      metabolism and relationships with cancer-related processes.

PMID- 22647266
TI  - Prodrome of delirium among long-term care residents: what clinical changes can be
      observed in the two weeks preceding a full-blown episode of delirium?
AB  - BACKGROUND: Delirium among long-term care (LTC) residents is frequent and is
      associated with increased morbidity and mortality. Identification of clinical
      changes during the prodromal phase of delirium could lead to prevention of a full
      blown episode and perhaps limit the deleterious consequences of this syndrome.
      The aim of the present study was to identify clinical changes observable in the 2
      week period prior to the onset of full-blown delirium. METHODS: Long-term care
      (LTC) residents aged 65 years and over, with or without dementia were eligible
      for this nested case-control study. Delirium was assessed weekly over a 6-month
      period using the Confusion Assessment Method. Cases with incident delirium were
      matched by time since enrollment to one or more controls without delirium.
      RESULTS: When compared to the controls, LTC residents who developed delirium
      (cases = 85) were more likely to have new-onset perceptual disturbances (OR =
      4.75; 95% CI 1.65-13.66) and disorganized thinking (OR = 3.09; 95% CI 1.33-7.19)
      and a worsening of the Mini-Mental State Examination (MMSE) item measuring
      registration (OR = 2.59; 95% CI 1.24-5.41) during the preceding 2 weeks. However,
      the frequency of these changes was low. Residents with at least 3 clinical
      changes were more likely to develop delirium than those without any clinical
      change (OR = 2.52; 95% CI 1.08-5.87). CONCLUSIONS: This study provides evidence
      of clinical changes during the prodromal phase of delirium among LTC residents.
      More studies are needed to further explore the role and relevance of these
      clinical changes as warning signs of imminent delirium.

PMID- 22647268
TI  - Combined dietary folate, vitamin B-12, and vitamin B-6 intake influences plasma
      docosahexaenoic acid concentration in rats.
AB  - BACKGROUND: Folate, vitamin B-12, and vitamin B-6 are essential nutritional
      components in one-carbon metabolism and are required for methylation capacity.
      The availability of these vitamins may therefore modify methylation of
      phosphatidylethanolamine (PE) to phosphatidylcholine (PC) by PE-N
      methyltransferase (PEMT) in the liver. It has been suggested that PC synthesis by
      PEMT plays an important role in the transport of polyunsaturated fatty acids
      (PUFAs) like docosahexaenoic acid (DHA) from the liver to plasma and possibly
      other tissues. We hypothesized that if B-vitamin supplementation enhances PEMT
      activity, then supplementation could also increase the concentration of plasma
      levels of PUFAs such as DHA. To test this hypothesis, we determined the effect of
      varying the combined dietary intake of these three B-vitamins on plasma DHA
      concentration in rats. METHODS: In a first experiment, plasma DHA and plasma
      homocysteine concentrations were measured in rats that had consumed a B-vitamin
      poor diet for 4 weeks after which they were either continued on the B-vitamin
      poor diet or switched to a B-vitamin-enriched diet for another 4 weeks. In a
      second experiment, plasma DHA and plasma homocysteine concentrations were
      measured in rats after feeding them one of four diets with varying levels of B
      vitamins for 4 weeks. The diets provided 0% (poor), 100% (normal), 400%
      (enriched), and 1600% (high) of the laboratory rodent requirements for each of
      the three B-vitamins. RESULTS: Plasma DHA concentration was higher in rats fed
      the B-vitamin-enriched diet than in rats that were continued on the B-vitamin
      poor diet (P = 0.005; experiment A). Varying dietary B-vitamin intake from
      deficient to supra-physiologic resulted in a non-linear dose-dependent trend for
      increasing plasma DHA (P = 0.027; experiment B). Plasma DHA was lowest in rats
      consuming the B-vitamin-poor diet (P > 0.05 vs. normal, P < 0.05 vs. enriched and
      high) and highest in rats consuming the B-vitamin-high diet (P < 0.05 vs. poor
      and normal, P > 0.05 vs. enriched). B-vitamin deficiency significantly increased
      plasma total homocysteine but increasing intake above normal did not
      significantly reduce it. Nevertheless, in both experiments plasma DHA was
      inversely correlated with plasma total homocysteine. CONCLUSION: These data
      demonstrate that dietary folate, vitamin B-12, and vitamin B-6 intake can
      influence plasma concentration of DHA.

PMID- 22647269
TI  - Medical students' perceptions of an emergency medicine clerkship: an analysis of
      self-assessment surveys.
AB  - BACKGROUND: No studies have been performed that evaluate the perceptions of
      medical students completing an emergency medicine (EM) clerkship. Given the
      variability of exposure to EM in medical schools nationwide, assessment of the
      student rotation may inform the structure and content of new and existing
      clerkships, particularly in relation to student's acquisition of the core
      competencies. OBJECTIVES: To investigate whether undergraduate medical students
      rotating through an EM clerkship improved their understanding and abilities in
      core content areas and common procedural skills; to evaluate whether improvement
      was affected by rotation length. METHODS: All students participating in an EM
      clerkship over a 12-month period were asked to complete an anonymous voluntary
      pre- and post-rotation survey. Confidence with patient assessment, diagnosis, and
      management plans; trauma and medical resuscitations; formal and informal
      presentations; basic procedure skills and understanding of the modern practice of
      EM were self assessed using a Likert scale. Group mean scores on each question on
      the pre- and post-clerkship surveys were calculated and compared. The mean scores
      on each survey item, both pre- and post-clerkship, were compared between 2- and 4
      week clerkship rotation groups. RESULTS: Two hundred thirty-nine students
      participated in the rotation during the 12 months of the study. One hundred sixty
      one (161), or 67.4%, completed the pre-rotation survey, and 96 (40.2%) completed
      the post-rotation survey. Overall, students showed significant mean gains in
      confidence with initial patient assessment, diagnosis, and management plans (p <
      0.01, 0.02, <0.01) and with basic procedure skills (p < 0.01 for all). Students
      completing a 2-week rotation did not differ significantly from f4week rotators in
      confidence levels, except in the area of formal presentation skills (p = 0.01),
      where the 4-week students demonstrated a statistically significant advantage. The
      2-week clerkship participants were significantly less confident in all procedures
      except EKG interpretation, splinting, and venipuncture (p = 0.28, 0.22, 0.05).
      Regardless of rotation length, students generally felt they had sufficient
      exposure to patients and opportunities for hands-on learning and practice, and
      overwhelmingly would recommend the EM clerkship to a fellow student, regardless
      of their chosen specialty. CONCLUSIONS: Medical students show significant gains
      in confidence with acute care knowledge, disease management, and procedure skills
      after completion of an EM clerkship. Although a 4-week clerkship may be
      preferable to expose students to the widest variety of patients and procedures,
      all students can benefit and improve in core competencies after an EM
      undergraduate experience.

PMID- 22647270
TI  - Enhanced influenza virus-like particle vaccines containing the extracellular
      domain of matrix protein 2 and a Toll-like receptor ligand.
AB  - The extracellular domain of matrix protein 2 (M2e) is conserved among influenza A
      viruses. The goal of this project is to develop enhanced influenza vaccines with
      broad protective efficacy using the M2e antigen. We designed a membrane-anchored
      fusion protein by replacing the hyperimmunogenic region of Salmonella enterica
      serovar Typhimurium flagellin (FliC) with four repeats of M2e (4.M2e-tFliC) and
      fusing it to a membrane anchor from influenza virus hemagglutinin (HA). The
      fusion protein was incorporated into influenza virus M1-based virus-like
      particles (VLPs). These VLPs retained Toll-like receptor 5 (TLR5) agonist
      activity comparable to that of soluble FliC. Mice immunized with the VLPs by
      either intramuscular or intranasal immunization showed high levels of systemic M2
      specific antibody responses compared to the responses to soluble 4.M2e protein.
      High mucosal antibody titers were also induced in intranasally immunized mice.
      All intranasally immunized mice survived lethal challenges with live virus, while
      intramuscularly immunized mice showed only partial protection, revealing better
      protection by the intranasal route. These results indicate that a combination of
      M2e antigens and TLR ligand adjuvants in VLPs has potential for development of a
      broadly protective influenza A virus vaccine.

PMID- 22647267
TI  - Global heterochromatin loss: a unifying theory of aging?
AB  - The aging field is replete with theories. Over the past years, many distinct, yet
      overlapping mechanisms have been proposed to explain organismal aging. These
      include free radicals, loss of heterochromatin, genetically programmed
      senescence, telomere shortening, genomic instability, nutritional intake and
      growth signaling, to name a few. The objective of this Point-of-View is to
      highlight recent progress on the "loss of heterochromatin" model of aging and to
      propose that epigenetic changes contributing to global heterochromatin loss may
      underlie the various cellular processes associated with aging.

PMID- 22647271
TI  - Prevalence of serum bactericidal antibody to serogroup C Neisseria meningitidis
      in England a decade after vaccine introduction.
AB  - Serogroup C meningococcal disease incidence and carriage declined rapidly in the
      United Kingdom after infant serogroup C conjugate vaccination was introduced in
      1999, with catch-up vaccination for children under 18 years. Antibody levels and
      effectiveness waned quickly in children vaccinated at 2, 3, and 4 months of age.
      Therefore, in 2006, the current revised schedule of doses at 3, 4, and 12 months
      was introduced. This study assessed age-specific protection in 2009 compared with
      data from historical prevaccination and early postvaccination studies. Rabbit
      complement serum bactericidal antibody (SBA) was measured in anonymously banked
      serum samples collected in England in 2009 (n = 1,174), taking titers of >= 8 as
      protective. Age-stratified proportions of SBA titers that were >= 8 and geometric
      mean titers were compared. SBA titers varied markedly by birth cohort and time
      since vaccination. Overall, 35% of samples (95% confidence interval [CI], 33 to
      38%) had titers that were >= 8. Only in cohorts eligible for catch-up vaccination
      did the majority of individuals have protective antibody levels. Antibody levels
      were higher in children eligible for vaccination at primary and secondary school
      ages, compared to those eligible below the age of 5 years. In those eligible for
      completed vaccination under the current schedule, protective levels were very
      modest and there was no evidence of superiority to cohorts that were eligible for
      the previous schedule. This supports a need for older childhood or adolescent
      booster vaccination in those previously eligible for vaccination during the
      infant, toddler, or preschool periods, to maintain direct protection and
      potentially enhance population immunity.

PMID- 22647272
TI  - Schiff bases of indoline-2,3-dione (isatin) with potential antiproliferative
      activity.
AB  - BACKGROUND: Cancer is one of the most dreaded diseases and it is a leading cause
      of mankind death worldwide. Recent reports documented a remarkable
      antiproliferative activity of isatin nucleus against various cancer cell lines.
      The current work describes the antiproliferative activity of Schiff bases of
      combinatorial mixtures of the isatin derivatives M1-M22 as well as the individual
      compounds 1-11(A-K) of these combinatorial mixtures. RESULTS: The designed
      combinatorial library composed from eleven hydrazides A-K and eleven isatin
      derivatives 1-11 has been synthesized to formally generate 22 mixtures, M1-M22 of
      121 Schiff bases, and their antiproliferative activity against K562 chronic
      myelogenous leukemia cells was evaluated. The indexed method of analysis of the
      prepared library was applied to elucidate the active components in the tested
      mixtures M1-M22. The predictions from the crossing procedure was validated
      through evaluation of the antiproliferative activity of individual compounds 1
      11(A-K) of the library. Individual compounds 1-11(A-K) were also evaluated
      against the non-tumorigenic MCF-12A cell line to investigate their selectivity. A
      pharmacophore model was developed to further optimize the antiproliferative
      activity among this series of compounds. CONCLUSIONS: Variable antiproliferative
      activity was revealed with the investigated mixtures M1-M22 and the individual
      compounds 1-11(A-K). Most of the tested mixtures and several individual Schiff
      bases displayed high potency with IC50 values in the low micromolar range. A
      considerable selectivity of some individual compounds to the tumorigenic K562
      cell line compared with the non-tumorigenic MCF-12A cell line was observed as
      indicated by their selectivity index (SI).

PMID- 22647274
TI  - Differences in early acetaminophen hepatotoxicity between obese ob/ob and db/db
      mice.
AB  - Clinical investigations suggest that hepatotoxicity after acetaminophen (APAP)
      overdose could be more severe in the context of obesity and nonalcoholic fatty
      liver disease. The pre-existence of fat accumulation and CYP2E1 induction could
      be major mechanisms accounting for such hepatic susceptibility. To explore this
      issue, experiments were performed in obese diabetic ob/ob and db/db mice.
      Preliminary investigations performed in male and female wild-type, ob/ob, and
      db/db mice showed a selective increase in hepatic CYP2E1 activity in female db/db
      mice. However, liver triglycerides in these animals were significantly lower
      compared with ob/ob mice. Next, APAP (500 mg/kg) was administered in female wild
      type, ob/ob, and db/db mice, and investigations were carried out 0.5, 2, 4, and 8
      h after APAP intoxication. Liver injury 8 h after APAP intoxication was higher in
      db/db mice, as assessed by plasma transaminases, liver histology, and terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. In db/db
      mice, however, the extent of hepatic glutathione depletion, levels of APAP
      protein adducts, c-Jun N-terminal kinase activation, changes in gene expression,
      and mitochondrial DNA levels were not greater compared with the other genotypes.
      Furthermore, in the db/db genotype plasma lactate and beta-hydroxybutyrate were
      not specifically altered, whereas the plasma levels of APAP-glucuronide were
      intermediary between wild-type and ob/ob mice. Thus, early APAP-induced
      hepatotoxicity was greater in db/db than ob/ob mice, despite less severe fatty
      liver and similar basal levels of transaminases. Hepatic CYP2E1 induction could
      have an important pathogenic role when APAP-induced liver injury occurs in the
      context of obesity and related metabolic disorders.

PMID- 22647273
TI  - Morphine withdrawal activates hypothalamic-pituitary-adrenal axis and heat shock
      protein 27 in the left ventricle: the role of extracellular signal-regulated
      kinase.
AB  - The negative affective states of withdrawal involve the recruitment of brain and
      peripheral stress circuitry [e.g., noradrenergic activity, induction of the
      hypothalamo-pituitary-adrenocortical (HPA) axis, and the expression and
      activation of heat shock proteins (Hsps)]. The present study investigated the
      role of extracellular signal-regulated protein kinase (ERK) and beta-adrenoceptor
      on the response of stress systems to morphine withdrawal by the administration of
      [amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile
      (SL327), a selective inhibitor of ERK activation, or propranolol (a beta
      adrenoceptor antagonist). Dependence on morphine was induced by a 7-day
      subcutaneous implantation of morphine pellets. Morphine withdrawal was
      precipitated on day 8 by the injection of naloxone (2 mg/kg s.c.). Plasma
      concentrations of adrenocorticotropin and corticosterone were determined by
      radioimmunoassay; noradrenaline (NA) turnover in left ventricle was determined by
      high-performance liquid chromatography; and catechol-O-methyl transferase (COMT)
      and Hsp27 expression and phosphorylation at Ser82 were determined by quantitative
      blot immunolabeling. Morphine-withdrawn rats showed an increase of NA turnover
      and COMT expression in parallel with an enhancement of adrenocorticotropin and
      plasma corticosterone concentrations. In addition, we observed an enhancement of
      Hsp27 expression and phosphorylation. Pretreatment with SL327 or propranolol
      significantly reduced morphine withdrawal-induced increases of plasma
      adrenocorticotropin and Hsp27 phosphorylation at Ser82 without any changes in
      plasma corticosterone levels. The present findings demonstrate that morphine
      withdrawal is capable of inducing the activation of HPA axis in parallel with an
      enhancement of Hsp27 expression and Hsp27 phosphorylation at Ser82 and suggest a
      role for beta-adrenoceptors and ERK pathways in mediating morphine-withdrawal
      activation of the HPA axis and cellular stress response.

PMID- 22647275
TI  - Biodegradable nanoparticles of methoxy poly(ethylene glycol)-b-poly( d, l
      lactide)/methoxy poly(ethylene glycol)- b-poly(epsilon-caprolactone) blends for
      drug delivery.
AB  - The effects of blend weight ratio and polyester block length of methoxy
      poly(ethylene glycol)-b-poly( d, l-lactide) (MPEG- b-PDLL)/methoxy poly(ethylene
      glycol)- b-poly(epsilon-caprolactone) (MPEG- b-PCL) blends on nanoparticle
      characteristics and drug release behaviors were evaluated. The blend
      nanoparticles were prepared by nanoprecipitation method for controlled release of
      a poorly water-soluble model drug, indomethacin. The drug-loaded nanoparticles
      were nearly spherical in shape. The particle size and drug loading efficiency
      slightly decreased with increasing MPEG- b-PCL blend weight ratio. Two distinct
      thermal decomposition steps from thermogravimetric analysis suggested different
      blend weight ratios. Thermal transition changes from differential scanning
      calorimetry revealed miscible blending between MPEG- b-PDLL and MPEG- b-PCL in an
      amorphous phase. An in vitro drug release study demonstrated that the drug
      release behaviors depended upon the PDLL block length and the blend weight ratios
      but not on PCL block length.

PMID- 22647276
TI  - Food choices in the presence of 'healthy' and 'unhealthy' eating partners.
AB  - Eating with others has been shown to influence the amount of food eaten in a meal
      or snack. We examined whether choosing food in the presence of another person who
      is choosing either predominantly low-energy-dense or high-energy-dense foods
      affects food choices. A between-subjects laboratory-based study was used. A group
      of 100 young females selected a lunch-time meal from a buffet consisting of a
      range of high-energy-dense and low-energy-dense foods, in the presence of an
      'unhealthy' eating partner (who chose predominantly high-energy-dense foods) or a
      'healthy' eating partner (who chose predominantly low-energy-dense foods) or when
      alone. Participants in the 'unhealthy' eating partner condition were
      significantly less likely to choose and consume a low-energy-dense food item
      (carrots), than when choosing alone or in the presence of a 'healthy' eater.
      Choice of high-energy-dense food did not differ across the conditions, nor did
      the total energy consumed. These data suggest that social influences on food
      choice are limited in this context but the presence of an 'unhealthy' eating
      partner may undermine intentions to consume low-energy-dense foods. 

PMID- 22647277
TI  - Functional assessment of the muscle-bone unit in the lower leg.
AB  - Based on the mechanostat theory and the muscle-bone hypothesis, a methodological
      assessment of the musculoskeletal status in health and disease should relate
      maximum muscle force in relation to bone mass and geometry. While useful (i.e.
      three-dimensional) measures of tibial bone parameters can be obtained by
      peripheral quantitative computed tomography (pQCT), intrinsic plantarflexor
      muscle force cannot be directly measured under in vivo condition in humans.
      Instead, tissue size, torque and ground reaction force have been used as proxy
      markers of intrinsic muscle force. However, most of these proxy markers are not
      or insufficiently representative of maximum force. Based on our recent research,
      we describe a novel approach for the assessment of the lower leg muscle-bone unit
      in health and disease. It incorporates multiple one-legged hopping (m1LH) to
      assess maximum voluntary ground reaction force acting on the forefoot (F(m1LH))
      and bone mineral content at the 14%-site of tibia length (vBMC(14%)) as assessed
      by pQCT. Using the quantitative relationship between these two variables in
      conjunction with F(m1LH) per body weight, we present a two-step quantitative
      diagnostic algorithm to discriminate between primary and secondary bone disorders
      in children and adults.

PMID- 22647278
TI  - Effects of jumping exercise on maximum ground reaction force and bone in 8- to 12
      year-old boys and girls: a 9-month randomized controlled trial.
AB  - OBJECTIVES: To assess adaptations of the lower leg muscle-bone unit in 8- to 12
      year-old children following a randomized controlled jumping exercise intervention
      for 9 months. METHODS: Twelve boys and 10 girls (INT) performed a supervised
      jumping protocol during the first 10 min of their regularly scheduled physical
      education class twice a week, while 11 boys and 12 girls (CON) completed the
      regular curriculum. We assessed maximum voluntary ground reaction force during
      multiple one-legged hopping (F(m1LH)), and tibial bone strength/geometry by
      peripheral quantitative computed tomography (pQCT) at the 4-, 14-, 38- and 66%
      site pre, intermediate, and post intervention. RESULTS: Whether increases in
      F(m1LH) (+2.1% points, P= 0.752), nor changes in bone strength/geometry (+1 to
      +3% points, 0.169<P<0.861), were significantly different for INT relative to CON.
      The relationship between F(m1LH) and volumetric bone mineral content at the 14%
      site (vBMC(14%)) was very strong for both groups, pre and post intervention
      (0.51<=R(2)<=0.88). However, changes in F(m1LH) and vBMC(14%) were not
      correlated. CONCLUSIONS: In children, growth and exercise did not increase
      maximum muscle force and bone strength in proportion to each other, meaning that
      the adaptive processes were not tightly coupled or follow different time courses.

PMID- 22647279
TI  - Effect of different collegiate sports on cortical bone in the tibia.
AB  - OBJECTIVES: The purpose of this study was to determine the effect of sports
      participation on cortical bone in the tibia. METHODS: 53 female collegiate
      athletes (25 cross-country, 16 soccer, and 12 volleyball) and 20 inactive
      controls had the left distal 20% tibia scanned by pQCT. Cortical volumetric BMD
      (vBMD) was measured within the cortical shell at the anterior, posterior, medial,
      and lateral regions and standard deviations were calculated. RESULTS: Total vBMD
      was greater in the control group (1161+/-5 mg/mm(3)) than each of the sports
      (p<0.05). Soccer players (1147+/-5 mg/mm(3)) had greater vBMD than volleyball
      players (1136+/-7 mg/mm(3)) (p<0.05), but similar to cross-country runners
      (1145+/-5 mg/mm(3)). Cortical thickness was greatest in soccer players (4.1+/-0.1
      mm), while cross-country and control subjects (3.8+/-0.1 mm) had greater
      thickness than volleyball players (3.4+/-0.1 mm)(p<0.05). Periosteal
      circumference was greater in volleyball players (71+/-1.4 mm) than soccer, cross
      country, and control subjects (68+/-0.9, 69+/-0.8, and 66+/-1 mm, respectively;
      all, p<0.05). vBMD variation within the cortical shell was greater among control
      subjects (70+/-6 mg/cm(3)) than each of the athlete groups, with soccer players
      having lower variation than cross country runners (within-in person SD 36+/-6
      mg/cm(3) and 54+/-5 mg/cm(3) respectively; p<0.05). CONCLUSION: These results
      indicate bone geometry and distribution within the cortical shell of the tibia
      varies depending upon sporting activities of young women.

PMID- 22647280
TI  - Chair rising exercise is more effective than one-leg standing exercise in
      improving dynamic body balance: a randomized controlled trial.
AB  - A randomized controlled trial was conducted to compare the effect of a one-leg
      standing exercise and a chair-rising exercise on body balance in patients with
      locomotive disorders. Thirty ambulatory patients (mean age: 66.6 years) were
      randomly divided into two groups (n=15 in each group): a one-leg standing
      exercise group and a chair-rising exercise group. All the participants performed
      calisthenics of the major muscles, a tandem gait exercise, and a stepping
      exercise. The exercises were performed 3 days per week, and the study period was
      5 months. Physical function was evaluated at baseline and at one-month intervals.
      No significant differences in the baseline characteristics were observed between
      the two groups. After the 5-month exercise program, the timed up and go, one-leg
      standing time, and tandem gait time improved significantly in the one-leg
      standing exercise group, while the walking time and chair-rising time in addition
      to above parameters improved significantly in the chair-rising exercise group.
      The improvements in the walking time, chair-rising time, and tandem gait time
      were significantly greater in the chair-rising exercise group than in the one-leg
      standing exercise group. The present study showed that the chair-rising exercise
      was more effective than the one-leg standing exercise for improving walking
      velocity and dynamic body balance.

PMID- 22647281
TI  - Muscle force and power in obese and overweight children.
AB  - The study investigated differences in skeletal muscle function between obese and
      non-obese children using a force platform. Forty obese children and adolescents
      (age range 8 to 18 years; 21 girls) and 40 age- and sex-matched controls
      performed two tests: (1) single two-legged jump, a countermovement jump for
      maximal height; (2) multiple one-legged hopping on the forefoot, a test of
      maximal force. In the single two-legged jump, obese subjects had higher absolute
      peak force (1.62 kN vs 1.09 kN) and peak power (2.46 kW vs 2.06 kW), but lower
      body weight-related peak force (2.10 vs 2.33) and lower peak power per body mass
      (30.9 W/kg vs 41.6 W/kg). Jump height (29.3 cm vs 37.5 cm) and maximal vertical
      velocity (1.92 ms(-1) vs 2.31 ms(-1)) were reduced in obese children. In multiple
      one-legged hopping, obese subjects had 72% and 84% higher absolute peak force on
      the left and right foot, respectively. However, forces relative to body weight
      were 24% and 23% lower in the obese group than in the control group. In
      conclusion, obese children and adolescents have increased muscle force and power.
      This partly compensates for the effect of high body weight on muscle performance.

PMID- 22647282
TI  - Serum leptin levels negatively correlate with trabecular bone mineral density in
      high-fat diet-induced obesity mice.
AB  - OBJECTIVES: This study evaluated the influence of diet-induced obesity on bone
      tissue quantity and quality in the proximal tibiae of growing mice and also
      examined the relationships between the serum total cholesterol, leptin, and
      adiponectin levels and trabecular and cortical bone mineral parameters. METHODS:
      Six-week-old male C57BL/6J mice were divided into two groups; one received a
      control diet, and the other received a high-fat-diet. After treatment for 4, 8,
      or 12 weeks, the bone quantity and quality were analyzed using peripheral
      quantitative computed tomography (pQCT), micro-computed tomography and
      histomorphometry. RESULTS: In the early stages, trabecular bone density decreased
      with an increase in the number of adipocytes and the deterioration of trabeculae.
      In contrast, although cortical bone formation was slower in obese mice compared
      with control mice, bone formation on the periosteal surface increased with age.
      Serum leptin levels were correlated with trabecular, but not cortical bone
      density, whereas neither the adiponectin nor total cholesterol level was
      correlated with bone mass in mice with diet-induced obesity. CONCLUSIONS: We
      conclude that bone loss at these two sites is differentially regulated in mice.
      Furthermore, we demonstrate that serum leptin may be a useful indicator of risk
      for osteoporosis associated with diet-induced obesity.

PMID- 22647283
TI  - Pressure pain thresholds at the diabetic Charcot-foot: an exploratory study.
AB  - OBJECTIVE: Painless mechanical trauma is believed to induce neuroosteoarthropathy
      at the neuropathic foot in diabetes (diabetic Charcot-foot). To investigate
      pressure nociception at the diabetic foot, we measured the pain perception
      thresholds for deep pressure (DPPPT, using Algometer II(r)) and cutaneous
      pressure (CPPPT, using calibrated monofilaments). METHODS: In 24 diabetic
      patients with painless neuropathy (11 with a chronic, inactive Charcot-foot and a
      history of foot ulcer, and 13 control patients who never had an ulcer), and in 20
      healthy subjects, CPPPT (at palmar and plantar digital skinfolds) and DPPPT (over
      musculus abductor pollicis, musculus hallucis longus, and over
      metacarpophalangeal and metatarsophalangeal joints) was measured. RESULTS: At the
      hands, DPPPT and CPPPT were similar in patients and healthy subjects. At the
      feet, CPPPT was above the upper safety limit of measurement (512 mN) in 2/20
      healthy subjects, and in 11/11 Charcot patients compared to 6/13 neuropathic
      controls (p=0.005). At the feet, median DPPPT was similar in all groups. In
      Charcot patients only, DPPPT was higher over metatarsophalangeal joint than over
      m. hallucis longus (p=0.048). CONCLUSION: Perception thresholds for cutaneous
      pressure pain, but not for deep pressure pain, may be extremely elevated at the
      diabetic neuropathic foot, and particularly at the Charcot-foot.

PMID- 22647285
TI  - Anxiety symptoms and suicidal feelings in a population sample of 70-year-olds
      without dementia.
AB  - BACKGROUND: The role of anxiety in late-life suicidal behavior has received
      relatively little attention. The aim was to explore the association between
      anxiety symptoms and suicidal feelings in a population sample of 70-year-olds
      without dementia, and to test whether associations would be independent of
      depression. METHODS: Face-to-face interviews (N = 560) were carried out by
      psychiatric nurses and past month symptoms were rated with the Comprehensive
      Psychopathological Rating Scale (CPRS). The Brief Scale for Anxiety (BSA) was
      derived from the CPRS to quantify anxiety symptom burden. Past month suicidal
      feelings were evaluated with the Paykel questions. RESULTS: Anxiety symptom
      burden was associated with suicidal feelings and the association remained after
      adjusting for major depression. One individual BSA item (Inner tension) was
      independently associated with suicidal feelings in a multivariate regression
      model. The association did not remain, however, in a final model in which
      depression symptoms replaced depression diagnosis. CONCLUSIONS: Results from this
      population study suggest an association between anxiety and suicidal feelings in
      older adults. The role of anxiety and depression symptoms needs further
      clarification in the study of suicidal behavior in late life.

PMID- 22647286
TI  - Psychosocial treatments for ADHD: a systematic appraisal of the evidence.
AB  - OBJECTIVE: Children with learning disabilities often experience comorbid ADHD,
      impacting on the effectiveness of interventions for those children. In addition
      to pharmacologic intervention, clinicians and educators employ a variety of
      psychosocial methods to address the behavioral and social issues that arise in
      children with ADHD, including those with co-occurring learning disabilities.
      Numerous systematic reviews and meta-analyses have been conducted examining
      treatment studies using psychosocial interventions for children with ADHD.
      Because of the importance of such reviews to evidence based clinical and
      educational practice, it is essential that reviews be conducted with rigorous
      methodologies to avoid bias in conclusions (Schlosser, Wendt, & Sigafoos, 2007).
      The purpose of this study was to evaluate the quality of systematic reviews and
      meta-analyses conducted for psychosocial treatments of ADHD in children. METHOD:
      Electronic databases were searched for peer-reviewed, English language studies of
      psychosocial treatments for ADHD in children up to 18-years-old from 1998 to
      2010. Twenty-one studies were identified that met inclusion criteria (13
      systematic reviews, 8 meta-analyses). Independent examiners used the quality
      rating scale proposed by Auperin, Pignon, and Pynard (1997) to rate the
      characteristics of good systematic reviews and meta-analyses. RESULTS: Results
      indicated that certain methodological characteristics were common across trials
      reviewed, yet shortcomings were common among most reviews, including inadequate
      descriptions of data extraction methods and lack of quality ratings for trials
      included in the reviews. CONCLUSION: Synthesis of findings from the five top
      rated reviews and the literature on ADHD suggest that psychosocial treatments
      contribute to improvements on behavioral and social outcomes. How ADHD and LD
      interplay in treatment outcomes is largely unexplored.

PMID- 22647287
TI  - An open trial of a metacognitive executive function training for young children
      with ADHD.
AB  - OBJECTIVE: Executive functioning is impaired in children with ADHD and putatively
      related to the pathogenesis of ADHD. The authors developed an innovative
      treatment teaching parents to administer a metacognitive executive function
      training intervention with children, promoting positive interactions during
      activities designed to improve attention and self-regulation. METHOD: A total of
      24 young children with ADHD and their parents participated in an 8-week open
      trial of the intervention designed to assess feasibility and initial efficacy.
      RESULTS: The intervention is feasible and accepted by parents as shown by high
      attendance/adherence, low attrition, and satisfaction ratings. Improvements in
      executive functions (visual/auditory attention, working memory, and cognitive
      flexibility) with corresponding improvements in parent ratings of executive
      functioning were observed. Reduced inattention symptoms were reported.
      CONCLUSION: Executive functioning training is a promising approach to treating
      young children with ADHD and holds promise for generalizability because parents
      are trained to be interventionists and coached to apply the strategies to
      alternative domains.

PMID- 22647288
TI  - Nonpharmacological treatments for ADHD: a meta-analytic review.
AB  - OBJECTIVE: The authors replicated and expanded on Fabiano et al.'s meta-analysis
      of behavioral treatments for ADHD, systematically comparing the efficacy of 7
      nonpharmacological interventions. METHOD: A total of 14 controlled treatment
      studies conducted post-1994-evaluating behavior modification, neurofeedback
      therapy, multimodal psychosocial treatment, school-based programs, working memory
      training, parent training, and self-monitoring-were identified, primarily by
      searching electronic English-language databases. The results were meta-analyzed:
      mean-weighted effect sizes for the treatment outcomes of 625 participants (382
      treatment, 243 controls) were calculated, and moderator analyses examined
      contributions of gender, ADHD subtype, and treatment "dosage" to outcome.
      RESULTS: Behavior modification and neurofeedback treatments were most supported
      by this evidence. Interventions were generally more efficacious for girls, and
      least efficacious for the "combined" ADHD subtype. The authors found no dose or
      age effects. CONCLUSION: Based on the small, published literature, this study
      supports some nonpharmacological interventions for ADHD, and indicates directions
      for more evaluation research into psychological treatments.

PMID- 22647289
TI  - Modulating epigenetic mechanisms: the diverse functions of Ski during cortical
      development.
AB  - In the developing forebrain, neural stem and progenitor cells generate a large
      variety of neurons with specific functions in the mature cortex. A central issue
      is to understand the roles of transcriptional networks and regulatory pathways
      that control these complex developmental processes. The proto-oncogene Ski is a
      transcriptional regulator linked to the human 1p36 deletion syndrome, which
      involves a set of phenotypes including nervous system defects. Ski shows a
      dynamic expression pattern during cortical development and, accordingly, the
      phenotype of Ski-deficient cortices is complex, involving altered cell cycle
      characteristics of neural progenitors, disturbed timing of neurogenesis and mis
      specification of projection neurons. Ski is likely to play a role in various
      pathways by virtue of its ability to interact with a range of signaling
      molecules, thereby modulating transcriptional activity of corresponding target
      genes. Ski regulates proliferation and differentiation of various cell types, and
      more recent data from my laboratory demonstrates that Ski is also involved in the
      specification of cortical projection neurons. This Point-of-View elucidates the
      role of Ski as an essential linker between sequence-specific transcription
      factors and non-DNA binding cofactors with chromatin modifying activities. In
      particular, it puts forward the hypothesis that the diverse functions of Ski as a
      co-repressor might be related to its association with distinct HDAC-complexes.

PMID- 22647290
TI  - Self-help materials for the prevention of smoking relapse: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Most people who stop smoking successfully for a few weeks will return
      to smoking again in the medium term. There are few effective interventions to
      prevent this relapse and none used routinely in clinical practice. A previous
      exploratory meta-analysis suggested that self-help booklets may be effective but
      requires confirmation. This trial aims to evaluate the effectiveness and cost
      effectiveness of a set of self-help educational materials to prevent smoking
      relapse in the National Health Service (NHS) Stop Smoking Service.
      METHODS/DESIGN: This is an open, randomized controlled trial. The target
      population is carbon monoxide (CO) verified quitters at four weeks in the NHS
      stop smoking clinic (total sample size N = 1,400). The experimental intervention
      tested is a set of eight revised Forever Free booklets, including an introduction
      booklet and more extensive information on all important issues for relapse
      prevention. The control intervention is a leaflet that has no evidence to suggest
      it is effective but is currently given to some patients using NHS stop smoking
      services. Two follow-up telephone interviews will be conducted at three and 12
      months after the quit date. The primary outcome will be prolonged abstinence from
      months four to 12 with no more than five lapses, confirmed by a CO test at the 12
      month assessment. The secondary outcomes will be seven-day self-report point
      prevalence abstinence at three months and seven-day biochemically confirmed point
      prevalence abstinence at 12 months. To assess cost-effectiveness, costs will be
      estimated from a health service perspective and the EQ-5D will be used to
      estimate the QALY (Quality Adjusted Life Year) gain associated with each
      intervention. The comparison of smoking abstinence rates (and any other binary
      outcomes) between the two trial arms will be carried out using odds ratio as the
      outcome statistic and other related statistical tests. Exploratory subgroup
      analyses, including logistic regression analyses with interaction terms, will be
      conducted to investigate possible effect-modifying variables. DISCUSSION: The
      possible effect of self-help educational materials for the prevention of smoking
      relapse has important public health implications. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN36980856.

PMID- 22647291
TI  - Three-dimensional quantitative structure activity relationship (QSAR) of
      cytotoxic active 3,5-diaryl-4,5-dihydropyrazole analogs: a comparative molecular
      field analysis (CoMFA) revisited study.
AB  - In vitro antitumor evaluation of the synthesized 46 compounds of 3,5-diaryl-4,5
      dihydropyrazoles against EAC cell lines and 3D QSAR study using pharmacophore and
      Comparative Molecular Field Analysis (CoMFA) methods were described. CoMFA
      derived QSAR model shows a good conventional squared correlation coefficient r2
      and cross validated correlation coefficient r2cv 0.896 and 0.568 respectively. In
      this analysis steric and electrostatic field contribute to the QSAR equation by
      70% and 30% respectively, suggesting that variation in biological activity of the
      compounds is dominated by differences in steric (van der Waals) interactions. To
      visualize the CoMFA steric and electrostatic field from partial least squares
      (PLS) analysis, contour maps are plotted as percentage contribution to the QSAR
      equation and are associated with the differences in biological activity.
      BACKGROUND: Pyrazole derivatives exhibit a wide range of biological properties
      including promising antitumor activity. Furthermore, Aldol condensation assisted
      organic synthesis has delivered rapid routes to N-containing heterocycles,
      including pyrazoles. Combining these features, the use of chalconisation-assisted
      processes will provide rapid access to a targeted dihydropyrazoles library
      bearing a hydrazino 3D QSAR study using pharmacophore and Comparative Molecular
      Field Analysis (CoMFA) methods were described for evaluation of antioxidant
      properties. RESULTS: Chalcones promoted 1 of the 2 steps in a rapid, convergent
      synthesis of a small library of hydrazinyl pyrazole derivatives, all of which
      exhibited significant antitumor activity against Ehrlich Ascites Carcinoma (EAC)
      human tumor cell line comparable to that of the natural anticancer doxorubicin,
      as a reference standard during this study. In order to understand the observed
      pharmacological properties, quantitative structure-activity relationship (3D
      QSAR) study was initiated. CONCLUSIONS: Chalcones heating provides a rapid and
      expedient route to a series of pyrazoles to investigate their chracterization
      scavenging properties. Given their favorable properties, in comparison with known
      anticancer, these pyrazole derivatives are promising leads for further
      development and optimization.

PMID- 22647292
TI  - Mechanisms of protein degradation in mantle muscle and proposed gill remodeling
      in starved Sepia officinalis.
AB  - Cephalopods have relatively high rates of protein synthesis compared to rates of
      protein degradation, along with minimal carbohydrate and lipid reserves. During
      food deprivation on board protein is catabolized as a metabolic fuel. The aim of
      the current study was to assess whether biochemical indices of protein synthesis
      and proteolytic mechanisms were altered in cuttlefish, Sepia officinalis, starved
      for 7 days. In mantle muscle, food deprivation is associated with a decrease in
      protein synthesis, as indicated by a decrease in the total RNA level and
      dephosphorylation of key signaling molecules, such as the eukaryote binding
      protein, 4E-BP1 (regulator of translation) and Akt. The ubiquitination-proteasome
      system (UPS) is activated as shown by an increase in the levels of proteasome
      beta-subunit mRNA, polyubiquitinated protein, and polyubiquitin mRNA. As well,
      cathepsin activity levels are increased, suggesting increased proteolysis through
      the lysosomal pathway. Together, these mechanisms could supply amino acids as
      metabolic fuels. In gill, the situation is quite different. It appears that
      during the first stages of starvation, both protein synthesis and protein
      degradation are enhanced in gill. This is based upon increased phosphorylation of
      4E-BP1 and enhanced levels of UPS indicators, especially 20S proteasome activity
      and polyubiquitin mRNA. It is proposed that an increased protein turnover is
      related to gill remodeling perhaps to retain essential hemolymph-borne compounds.

PMID- 22647293
TI  - Role of small conductance calcium-activated potassium channels expressed in PVN
      in regulating sympathetic nerve activity and arterial blood pressure in rats.
AB  - Small conductance Ca(2+)-activated K(+) (SK) channels regulate membrane
      properties of rostral ventrolateral medulla (RVLM) projecting hypothalamic
      paraventricular nucleus (PVN) neurons and inhibition of SK channels increases in
      vitro excitability. Here, we determined in vivo the role of PVN SK channels in
      regulating sympathetic nerve activity (SNA) and mean arterial pressure (MAP). In
      anesthetized rats, bilateral PVN microinjection of SK channel blocker with
      peptide apamin (0, 0.125, 1.25, 3.75, 12.5, and 25 pmol) increased splanchnic SNA
      (SSNA), renal SNA (RSNA), MAP, and heart rate (HR) in a dose-dependent manner.
      Maximum increases in SSNA, RSNA, MAP, and HR elicited by apamin (12.5 pmol, n =
      7) were 330 +/- 40% (P < 0.01), 271 +/- 40% (P < 0.01), 29 +/- 4 mmHg (P < 0.01),
      and 34 +/- 9 beats/min (P < 0.01), respectively. PVN injection of the nonpeptide
      SK channel blocker UCL1684 (250 pmol, n = 7) significantly increased SSNA (P <
      0.05), RSNA (P < 0.05), MAP (P < 0.05), and HR (P < 0.05). Neither apamin
      injected outside the PVN (12.5 pmol, n = 6) nor peripheral administration of the
      same dose of apamin (12.5 pmol, n = 5) evoked any significant changes in the
      recorded variables. PVN-injected SK channel enhancer 5,6-dichloro-1-ethyl-1,3
      dihydro-2H-benzimidazol-2-one (DCEBIO, 5 nmol, n = 4) or N-cyclohexyl-N-[2-(3,5
      dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidin]amine (CyPPA, 5 nmol, n = 6) did not
      significantly alter the SSNA, RSNA, MAP, and HR. Western blot and RT-PCR analysis
      of punched PVN tissue showed abundant expression of SK1-3 channels. We conclude
      that SK channels expressed in the PVN play an important role in the regulation of
      sympathetic outflow and cardiovascular function.

PMID- 22647294
TI  - Possible role of brain salt-inducible kinase 1 in responses to central sodium in
      Dahl rats.
AB  - In Dahl salt-sensitive (S) rats, Na(+) entry into the cerebrospinal fluid (CSF)
      and sympathoexcitatory and pressor responses to CSF Na(+) are enhanced. Salt
      inducible kinase 1 (SIK1) increases Na(+)/K(+)-ATPase activity in kidney cells.
      We tested the possible role of SIK1 in regulation of CSF [Na(+)] and responses to
      Na(+) in the brain. SIK1 protein and activity were lower in hypothalamic tissue
      of Dahl S (SS/Mcw) compared with salt-resistant SS.BN13 rats.
      Intracerebroventricular infusion of the protein kinase inhibitor staurosporine at
      25 ng/day, to inhibit SIK1 further increased mean arterial pressure (MAP) and HR
      but did not affect the increase in CSF [Na(+)] or hypothalamic aldosterone in
      Dahl S on a high-salt diet. Intracerebroventricular infusion of Na(+)-rich
      artificial CSF caused significantly larger increases in renal sympathetic nerve
      activity, MAP, and HR in Dahl S vs. SS.BN13 or Wistar rats on a normal-salt diet.
      Intracerebroventricular injection of 5 ng staurosporine enhanced these responses,
      but the enhancement in Dahl S rats was only one-third that in SS.BN13 and Wistar
      rats. Staurosporine had no effect on MAP and HR responses to
      intracerebroventricular ANG II or carbachol, whereas the specific protein kinase
      C inhibitor GF109203X inhibited pressor responses to intracerebroventricular
      Na(+)-rich artificial CSF or ANG II. These results suggest that the SIK1
      Na(+)/K(+)-ATPase network in neurons acts to attenuate sympathoexcitatory and
      pressor responses to increases in brain [Na(+)]. The lower hypothalamic SIK1
      activity and smaller effect of staurosporine in Dahl S rats suggest that impaired
      activation of neuronal SIK1 by Na(+) may contribute to their enhanced central
      responses to sodium.

PMID- 22647295
TI  - Hypertension in response to CD4(+) T cells from reduced uterine perfusion
      pregnant rats is associated with activation of the endothelin-1 system.
AB  - We have shown that adoptive transfer of CD4(+) T cells from placental ischemia
      (reduction in uteroplacental perfusion, RUPP) rats causes hypertension and
      elevated inflammatory cytokines during pregnancy. In this study we tested the
      hypothesis that adoptive transfer of RUPP CD4(+) T cells was associated with
      endothelin-1 activation as a mechanism to increase blood pressure during
      pregnancy. CD4(+) T cells from RUPP or normal pregnant (NP) rats were adoptively
      transferred into NP rats on gestational day 13. Mean arterial pressure (MAP) was
      analyzed on gestational day 19, and tissues were collected for endothelin-1
      analysis. MAP increased in placental ischemic RUPP rats versus NP rats (124.1 +/-
      3 vs. 96.2 +/- 3 mmHg; P = 0.0001) and increased in NP recipients of RUPP CD4(+)
      T cells (117.8 +/- 2 mmHg; P = 0.001 compared with NP). Adoptive transfer of RUPP
      CD4(+) T cells increased placental preproendothelin-1 mRNA 2.1-fold compared with
      NP CD4(+) T cell rats and 1.7-fold compared with NP. Endothelin-1 secretion from
      endothelial cells exposed to NP rat serum was 52.2 +/- 1.9 pg.mg(-1).ml(-1), 77.5
      +/- 4.3 pg.mg(-1).ml(-1) with RUPP rat serum (P = 0.0003); 47.2 +/- .16 pg.mg(
      1).ml(-1) with NP+NP CD4(+) T cell serum, and 62.2 +/- 2.1 pg.mg(-1).ml(-1) with
      NP+RUPP CD4(+) T cell serum (P = 0.002). To test the role of endothelin-1 in RUPP
      CD4(+) T cell-induced hypertension, pregnant rats were treated with an endothelin
      A (ET(A)) receptor antagonist (ABT-627, 5 mg/kg) via drinking water. MAP was 92
      +/- 2 mmHg in NP+ET(A) blockade and 108 +/- 3 mmHg in RUPP+ET(A) blockade; 95 +/-
      5 mmHg in NP+NP CD4(+) T cells+ET(A) blockade and 102 +/- 2 mmHg in NP+RUPP
      CD4(+) T cells+ET(A) blockade. These data indicate the importance of endothelin-1
      activation to cause hypertension via chronic exposure to activated CD4(+) T cells
      in response to placental ischemia.

PMID- 22647296
TI  - From A to Z: a potential role for grid cells in spatial navigation.
AB  - Since their discovery, the strikingly regular and spatially stable firing of
      entorhinal grid cells has attracted the attention of experimentalists and
      theoreticians alike. The bulk of this work has focused either on the assumption
      that the principal role of grid cells is to support path integration or the
      extent to which their multiple firing locations can drive the sparse activity of
      hippocampal place cells. Here, we propose that grid cells are best understood as
      part of a network that combines self-motion and environmental cues to accurately
      track an animal's location in space. Furthermore, that grid cells - more so than
      place cells - efficiently encode self-location in allocentric coordinates.
      Finally, that the regular structure of grid firing fields represents information
      about the relative structure of space and, as such, may be used to guide goal
      directed navigation.

PMID- 22647297
TI  - Transcriptional regulation of cholesterol and bile acid metabolism after dietary
      soyabean meal treatment in Atlantic salmon (Salmo salar L.).
AB  - Inclusion of plant protein sources such as soyabean meal (SBM) in aquafeeds is
      associated with decreased lipid digestibility, reduced bile acid levels and
      hypocholesterolaemia. The mechanism for these metabolic abnormalities is unknown.
      The present study aimed at gaining further insight into how cholesterol and bile
      acid metabolism is modulated by SBM feeding by quantifying a number of mRNA
      species corresponding to key proteins involved in cholesterol and bile acid
      metabolism using quantitative real-time PCR. A 21 d feeding trial with sequential
      sampling at ten time points following initiation of 20% SBM exposure was
      conducted on Atlantic salmon. A histological evaluation confirmed distal
      intestinal enteritis after 5 d of dietary exposure to the SBM, whereas diminished
      glycogen/lipid deposition was the only relevant finding observed in the liver.
      SBM inclusion resulted in reduced body pools of cholesterol and bile acids.
      Hepatic gene expression profiles revealed up-regulation of genes encoding rate
      limiting enzymes in cholesterol (3-hydroxy-3-methyl-glutaryl-CoA reductase;
      HMGCR) and bile acid (cytochrome P4507A1 (CYP7A1)) biosynthesis, as well as up
      regulation of their associated transcription factors (sterol regulatory element
      binding proteins 1 and 2, liver X receptor, farnesoid X receptor and PPAR
      isoforms). Hepatic gene expressions of cholesterol (ATP binding cassette G5
      (ABCG5)) and bile acid (ATP binding cassette B11 (ABCB11)) transporters were, by
      and large, not influenced by the SBM, but distal intestinal expression patterns
      of ABCG5 and apical Na-dependent bile acid transporter indicated impaired
      cholesterol and bile acid reabsorption. In conclusion, hepatic gene expression
      profiles indicated that the capacity for cholesterol and bile acid synthesis was
      up-regulated, whereas the indicated impaired cholesterol and bile acid
      reabsorption probably occurred as a direct result of distal intestinal
      inflammation.

PMID- 22647298
TI  - Analysis of coronary flow haemodynamics in homozygous familial
      hypercholesterolaemic adolescents with aortic supravalvular stenosis.
AB  - OBJECTIVE: To study coronary artery haemodynamics in adolescents with homozygous
      familial hypercholesterolaemia and aortic supravalvular stenosis. METHODS:
      Patients diagnosed with familial hypercholesterolaemia who were younger than 16
      years and who had undergone transthoracic echocardiography from 2007 to 2010 were
      included in this study. We included patients with homozygous familial
      hypercholesterolaemia and aortic supravalvular stenosis and those with
      heterozygous familial hypercholesterolaemia. All patients underwent stress
      echocardiography, and left anterior descending coronary artery flow was
      successfully detected. Coronary flow velocity reserve was calculated as the ratio
      of hyperaemic mean diastolic flow velocity after injection of adenosine to basal
      mean diastolic flow velocity. Changes in coronary haemodynamics and the
      relationship between lipid concentrations were determined. RESULTS: A total of 11
      patients with homozygous familial hypercholesterolaemia were enrolled in this
      study. Lipid concentrations were measured, and the mean coronary flow velocity
      reserve was 1.97 plus or minus 0.51. Seven children were included in the group of
      patients with heterozygous familial hypercholesterolaemia. In these children, the
      mean coronary flow velocity reserve was 3.08 plus or minus 0.84. CONCLUSION: The
      coronary flow velocity reserve of homozygous familial hypercholesterolaemic
      patients is lower than that of heterozygous familial hypercholesterolaemic
      patients, and it is associated with a high concentration of low-density
      lipoprotein cholesterol. Aortic stenosis and plaques compromised the ostia of the
      coronary artery and caused increased basal mean diastolic coronary velocity with
      blunted increase in peak velocity, which decreased the coronary flow velocity
      reserve.

PMID- 22647299
TI  - Brain PET imaging in obesity and food addiction: current evidence and hypothesis.
AB  - The ongoing epidemics of obesity is one main health concern of the present time.
      Overeating in some obese individuals shares similarities with the loss of control
      and compulsive behavior observed in drug-addicted subjects, suggesting that
      obesity may involve food addiction. Here, we review the contributions provided by
      the use of positron emission tomography to the current understanding of the
      cerebral control of obesity and food intake in humans. The available studies have
      shown that multiple areas in the brain are involved with the reward properties of
      food, such as prefrontal, orbitofrontal, somatosensory cortices, insula,
      thalamus, hypothalamus, amygdala, and others. This review summarizes the current
      evidence, supporting the concepts that i) regions involved in the somatosensory
      response to food sight, taste, and smell are activated by palatable foods and may
      be hyperresponsive in obese individuals, ii) areas controlling executive drive
      seem to overreact to the anticipation of pleasure during cue exposure, and iii)
      those involved in cognitive control and inhibitory behavior may be resistant to
      the perception of reward after food exposure in obese subjects. All of these
      features may stimulate, for different reasons, ingestion of highly palatable and
      energy-rich foods. Though these same regions are similarly involved in drug
      abusers and game-addicted individuals, any direct resemblance may be an
      oversimplification, especially as the heterogeneities between studies and the
      prevalent exclusion of sensitive groups still limit a coherent interpretation of
      the findings. Further work is required to comprehensively tackle the multifaceted
      phenotype of obesity and identify the role of food dependency in its
      pathophysiology.

PMID- 22647301
TI  - Towards an animal model of food addiction.
AB  - The dramatically increasing prevalence of obesity, associated with potentially
      life-threatening health problems, including cardiovascular diseases and type II
      diabetes, poses an enormous public health problem. It has been proposed that the
      obesity epidemic can be explained by the concept of 'food addiction'. In this
      review we focus on possible similarities between binge eating disorder (BED),
      which is highly prevalent in the obese population, and drug addiction. Indeed,
      both behavioral and neural similarities between addiction and BED have been
      demonstrated. Behavioral similarities are reflected in the overlap in DSM-IV
      criteria for drug addiction with the (suggested) criteria for BED and by food
      addiction-like behavior in animals after prolonged intermittent access to
      palatable food. Neural similarities include the overlap in brain regions involved
      in food and drug craving. Decreased dopamine D2 receptor availability in the
      striatum has been found in animal models of binge eating, after cocaine self
      administration in animals as well as in drug addiction and obesity in humans. To
      further explore the neurobiological basis of food addiction, it is essential to
      have an animal model to test the addictive potential of palatable food. A
      recently developed animal model for drug addiction involves three behavioral
      characteristics that are based on the DSM-IV criteria: i) extremely high
      motivation to obtain the drug, ii) difficulty in limiting drug seeking even in
      periods of explicit non-availability, iii) continuation of drug-seeking despite
      negative consequences. Indeed, it has been shown that a subgroup of rats, after
      prolonged cocaine self-administration, scores positive on these three criteria.
      If food possesses addictive properties, then food-addicted rats should also meet
      these criteria while searching for and consuming food. In this review we discuss
      evidence from literature regarding food addiction-like behavior. We also suggest
      future experiments that could further contribute to our understanding of
      behavioral and neural commonalities and differences between obesity and drug
      addiction.

PMID- 22647300
TI  - Does food addiction exist? A phenomenological discussion based on the psychiatric
      classification of substance-related disorders and addiction.
AB  - The relationship between overeating, substance abuse and (behavioral) addiction
      is controversial. Medically established forms of addiction so far pertain to
      substance use disorders only. But the preliminary Diagnostic and Statistical
      Manual for Mental Disorders V (DSM V) suggests replacing the previous category
      'Substance-Related Disorders' with 'Addiction and Related Disorders', thus for
      the first time allowing the diagnosis of behavioral addictions. In the past
      psychiatrists and psychologists have been reluctant to systematically delineate
      and classify the term behavioral addiction. However, there is a broad overlap
      between chemical and behavioral addiction including phenomenological,
      therapeutic, genetic, and neurobiological aspects. It is of interest to point out
      that the hormone leptin in itself has a pronounced effect on the reward system,
      thus suggesting an indirect link between overeating and 'chemical' addiction.
      Thus, leptin-deficient individuals could be classified as fulfilling criteria for
      food addiction. In our overview we first review psychological findings in
      chemical (substance-based) and subsequently in behavioral addiction to analyze
      the overlap. We discuss the diagnostic validity of food addiction, which in
      theory can be chemically and/or behaviorally based.

PMID- 22647302
TI  - The opioid system and food intake: homeostatic and hedonic mechanisms.
AB  - Opioids are important in reward processes leading to addictive behavior such as
      self-administration of opioids and other drugs of abuse including nicotine and
      alcohol. Opioids are also involved in a broadly distributed neural network that
      regulates eating behavior, affecting both homeostatic and hedonic mechanisms. In
      this sense, opioids are particularly implicated in the modulation of highly
      palatable foods, and opioid antagonists attenuate both addictive drug taking and
      appetite for palatable food. Thus, craving for palatable food could be considered
      as a form of opioid-related addiction. There are three main families of opioid
      receptors (u, K, and delta) of which u-receptors are most strongly implicated in
      reward. Administration of selective u-agonists into the NAcc of rodents induces
      feeding even in satiated animals, while administration of u-antagonists reduces
      food intake. Pharmacological studies also suggest a role for K- and delta-opioid
      receptors. Preliminary data from transgenic knockout models suggest that mice
      lacking some of these receptors are resistant to high-fat diet-induced obesity.

PMID- 22647303
TI  - Neural substrates underlying interactions between appetite stress and reward.
AB  - Neurobiological mechanisms that normally control food intake and energy
      expenditure can be overcome by environmental cues and by stress. Of particular
      importance is the influence of the mesolimbic reward pathway. In genetically
      susceptible individuals, problematic over-eating likely reflects a changing
      balance in the control exerted by homeostatic versus reward circuits that are
      strongly influenced by environmental factors such as stress. Both stress and
      activation of the reward pathway have been shown to increase food intake and
      promote a preference for palatable, high-energy foods. Recent research has
      focused on the important role of circulating and central neuropeptides that
      powerfully regulate the brain response to food cues. For example, ghrelin has a
      potent positive effect on the motivational aspects of food intake, and central
      oxytocin may be involved in satiety. Thus, the decision to eat, or indeed to over
      eat, involves a complex integrated neurobiology that includes brain centres
      involved in energy balance, reward and stress and their regulation by metabolic
      and endocrine factors.

PMID- 22647304
TI  - Dietary factors affect food reward and motivation to eat.
AB  - The propensity to indulge in unhealthy eating and overconsumption of palatable
      food is a crucial determinant in the rising prevalence of obesity in today's
      society. The tendency to consume palatable foods in quantities that exceed energy
      requirements has been linked to an addiction-like process. Although the existence
      of 'food addiction' has not been conclusively proven, evidence points to
      alterations in the brain reward circuitry induced by overconsumption of palatable
      foods that are similar to those seen in drug addiction. The diet-induced obesity
      paradigm is a common procedure to replicate features of human obesity in rodents.
      Here we review data on the effect of various obesogenic diets (high-fat,
      EnsureTM, cafeteria type, sucrose) on the extent of leptin resistance,
      hypothalamic-neuropeptidergic adaptations and changes in feeding behavior. We
      also discuss to what extent such diets and properties such as macronutrient
      composition, physical structure, sensory stimuli, and post-ingestive effects
      influence the brain-reward pathways. Understanding the interaction between
      individual components of diets, feeding patterns, and brain reward pathways could
      facilitate the design of diets that limit overconsumption and prevent weight
      gain.

PMID- 22647305
TI  - Functional neuroimaging in craniopharyngioma: a useful tool to better understand
      hypothalamic obesity?
AB  - OBJECTIVE: To use functional magnetic resonance imaging (fMRI) in
      craniopharyngioma (CP) patients to examine the hypothesis that hypothalamic
      damage due to CP and its treatment results in enhanced perception of food reward
      and/or impaired central satiety processing. METHODS: Pre- and post-meal responses
      to visual food cues in brain regions of interest (ROI; bilateral nucleus
      accumbens, bilateral insula, and medial orbitofrontal cortex) were assessed in 4
      CP patients versus 4 age- and weight-matched controls. Stimuli consisted of
      images of high- ('fattening') and low-calorie ('non-fattening') foods in blocks,
      alternating with non-food object blocks. After the first fMRI scan, subjects
      drank a high-calorie test meal to suppress appetite, then completed a second fMRI
      scan. Within each ROI, we calculated mean z-scores for activation by fattening as
      compared to non-fattening food images. RESULTS: Following the test meal, controls
      showed suppression of activation by food cues while CP patients showed trends
      towards higher activation. CONCLUSION: These data, albeit in a small group of
      patients, support our hypothesis that perception of food cues may be altered in
      hypothalamic obesity (HO), especially after eating, i.e. in the satiated state.
      The fMRI approach is encouraging for performing future mechanistic studies of the
      brain response to food cues and satiety in patients with hypothalamic or other
      forms of childhood obesity.

PMID- 22647306
TI  - Severe obesity: the neglected epidemic.
AB  - Severe obesity (SO) is increasing faster than obesity in adults and in children.
      Because it is associated with numerous comorbidities, SO accounts for more health
      care expenditures than any other medical condition. Furthermore, it is associated
      with poor pregnancy outcomes for mother, fetus, and infant and a high risk of
      offspring obesity carried into adulthood. Bariatric surgery is the treatment of
      choice for SO because nonoperative methods fail to provide medically significant
      durable weight loss and because it is both preventive and therapeutic. The number
      of operations has sharply increased globally, yet only a small fraction of
      eligible patients are referred for surgical treatment demonstrating the need for
      improved access, especially for those disproportionately affected by SO. The
      risks of surgery mandate careful postoperative long-term multidisciplinary follow
      up care. Education is critical for truly informed consent and must continue
      postoperatively, especially for women with reproductive potential. Even so,
      surgical treatment of SO remains cost-effective compared to conventional
      nonoperative treatment, which also requires long-term care. Just as obesity
      affects all medical disciplines (from allergology and immunology to oncology,
      urology and women's health), so does postoperative management of bariatric
      surgery patients. We offer wide-ranging recommendations for policymakers and
      others to consider in addressing SO.

PMID- 22647307
TI  - The impact of type 2 diabetes on circulating adipokines in patients with
      metabolic syndrome.
AB  - AIM: The aim of the study was to investigate, whether type 2 diabetes
      independently influences adipokines and inflammatory markers in patients with
      metabolic syndrome. METHODS: 36 patients with metabolic syndrome without type 2
      diabetes and 39 patients with metabolic syndrome with type 2 diabetes, carefully
      matched for age, sex, and BMI, were investigated. Primary outcome measures were
      circulating adipokines and inflammatory markers (adiponectin, leptin, visfatin,
      vaspin, resistin, TNF-alpha, IL-6, monocyte chemoattractant protein-1 (MCP-1),
      retinol binding protein 4 (RBP-4), growth differentiation factor-15 (GDF-15)). In
      addition, we determined parameters of glucose and lipid metabolism. RESULTS:
      Patients with metabolic syndrome and type 2 diabetes had significantly lower
      levels of plasma total cholesterol, low-density lipoprotein cholesterol and
      triglycerides (p < 0.05). They displayed higher GDF-15 concentrations (1,113 +/-
      135 vs. 656 +/- 63 pg/ml, p = 0.005) and lower visfatin concentrations (3.7 +/-
      0.3 vs. 4.8 +/- 0.2 ng/ml, p = 0.009). There were no differences in other
      adipokines and inflammatory markers between both groups. CONCLUSIONS: In patients
      with metabolic syndrome, type 2 diabetes leads to decreased visfatin and
      increased GDF-15 serum levels when compared to carefully matched non-diabetic
      subjects. Whether the increase in GDF-15 is an indicator or a causal factor for
      the increased cardiovascular risk in diabetic subjects remains to be investigated
      in further studies.

PMID- 22647308
TI  - Stress and eating behaviour: implications for obesity.
AB  - BACKGROUND: This report outlines our strategy to examine the influence of
      workplace stress on eating behaviour, discussing the current literature which
      explores the relationship between stress and eating behaviour. This research aims
      to add to and develop the current understanding of the links between stress and
      eating behaviour. Specifically the aims are to examine the effect of workplace
      stress in both day workers and shift workers and their subsequent eating
      behaviour. METHODS: The effect of healthy working environment initiatives on
      stress and eating behaviour will also be examined by comparing a workplace with
      such an initiative to one with no such initiative. The role of personality on
      both eating behaviour and stress susceptibility will be examined. In order to
      achieve this, 450 individuals from 3 public sector workplaces will be recruited.
      Anthropometric measurements (waist-hip ratio, BMI, visceral fat percentage) will
      be assessed, as well as personality, eating behaviour profiles, food intake (7
      day weighed intake food diary) and both individual daily stressors as well as
      workplace stress assessed using the demand/control model of job strain will be
      assessed. CONCLUSIONS: Implications for policy and future research are also
      discussed.

PMID- 22647309
TI  - Shining the 'spotlight' on obesity.

PMID- 22647310
TI  - NeuroFAST - the integrated neurobiology of food intake, addiction and stress.

PMID- 22647311
TI  - What is the value of obesity research? - Comment on Blundell JE, Hebebrand J,
      Oppert JM. What is the value of obesity research? Obes Facts 2010;3:279-282.

PMID- 22647312
TI  - (Zn,H)-codoped copper oxide nanoparticles via pulsed laser ablation on Cu-Zn
      alloy in water.
AB  - Nanosized (5 to 10 nm) amorphous and crystalline nanocondensates, i.e., metallic
      alpha-phase of Zn-Cu alloy in face-centered cubic structure and (Zn,H)-codoped
      cuprite (Cu2O) with high-pressure-favored close-packed sublattice, were formed by
      pulsed laser ablation on bulk Cu65Zn35 in water and characterized by X
      ray/electron diffractions and optical spectroscopy. The as-fabricated hybrid
      nanocondensates are darkish and showed photoluminescence in the whole visible
      region. Further dwelling of such nanocondensates in water caused progressive
      formation of a rice-like assembly of (Zn,H)-codoped tenorite (CuO) nanoparticles
      with (001), (100), and {111} preferred orientations, (111) tilt boundary,
      yellowish color, and minimum bandgap narrowing down to ca. 2.7 eV for potential
      photocatalytic applications.

PMID- 22647313
TI  - A big new job for small GTPases.
AB  - Members of the Ras superfamily of small guanosine triphosphatases (GTPases)
      function as key nodes within signaling networks in a remarkable range of cellular
      processes, including cell proliferation, differentiation, growth, cell-cell
      adhesion and apoptosis. We recently described a novel role for the Ras-like small
      GTPases Rap1 and Ral in regulating cortical polarity and spindle orientation
      during asymmetric neuroblast division in Drosophila. The participation of these
      proteins in promoting cell polarization seems to be a common theme throughout
      evolution.

PMID- 22647315
TI  - Synthesis and antifungal activity of novel pyrazolecarboxamide derivatives
      containing a hydrazone moiety.
AB  - BACKGROUND: The plant pathogenic fungus (such as Gibberella zeae, Fusarium
      oxysporum and Cytospora mandshurica) causes devastating disease in agriculture.
      The pathogenic fungus is responsible for billions of dollars in economic losses
      worldwide each year. In order to discover new fungicidal molecule with good
      fungicidal activity against G. zeae, F. oxysporum, and C. mandshurica, we sought
      to combine the active sub-structure of hydrazone and pyrazole amide derivatives
      together to design and synthesize novel pyrazole amide derivatives containing a
      hydrazone moiety. RESULTS: A series of novel pyrazole amide derivatives bearing
      hydrazone moiety were synthesized. Their structures were characterized by 1 H
      NMR, 13 C-NMR, IR, and elemental analysis. The preliminary biological assays
      revealed that most of the synthesized compounds exhibit favorable antifungal
      activities against G. zeae. The activity of compounds 7a, 7f, 7g, 7h, 7i, 7j, 7l
      and 7q were 40.82%, 47.78%, 50.32%, 40.82%, 49.05%, 48.73%, 40.19% and 45.89%,
      respectively, and the synthesized compounds showed certain antifungal activities
      against F. oxysporum and C.mandshurica. CONCLUSION: A practical synthetic route
      to pyrazole amide derivatives containing a hydrazone moiety were synthesized by
      the condensation of intermediates 5-chloro-N-(4-subsititued-2-(hydrazinecarbonyl)
      6-methylphenyl)-1,3-dimethyl-1 H-pyrazole-4-carboxamide with different aldehydes
      or ketones in ethanol at room temperature is presented, the results of the study
      suggested that the pyrazole amide derivatives containing hydrazone moieties could
      inhibit the growth of G. zeae, F. oxysporium and C. mandshurica to a certain
      extent.

PMID- 22647314
TI  - Transfer of manualized CBT for social phobia into clinical practice (SOPHO-PRAX):
      a study protocol for a cluster-randomized controlled trial.
AB  - BACKGROUND: Cognitive-behavioral therapy (CBT) is generally known to be
      efficacious in the treatment of social phobia when applied in RCTs, namely when
      the treatment manual is based on the Clark-Wells approach. However, little is
      known about the efficacy of manualized treatments in routine clinical practice
      (Phase IV of psychotherapy research). The present study (SOPHO-PRAX) is a
      continuation of a large multicenter randomized clinical trial (SOPHO-NET) and
      analyzes the extent to which additional training practitioners in manualized
      procedures enhances treatment effect. METHODS/DESIGN: Thirty-six private
      practitioners will be included in three treatment centers and randomly designated
      to either training in manualized CBT or no specific training. The treatment
      effects of the therapies conducted by both groups of therapists will be compared.
      A total of 162 patients (n=116 completers; n=58 per condition) will be enrolled.
      Liebowitz Social Anxiety Scale (LSAS) will serve as primary outcome measure.
      Remission from social phobia is defined as LSAS total <= 30 points. Data will be
      collected at treatment begin, after 8, 15, and 25 sessions (50 min each), at
      treatment completion, as well at 6 and 12 months post-treatment. DISCUSSION: The
      present CBT trial combines elements of randomized controlled trials and
      naturalistic studies in an innovative way. It will directly inform about the
      incremental effects of procedures established in a controlled trial into clinical
      practice. Study results are relevant to healthcare decisions and policy. They may
      serve to improve quality of treatment, and shorten the time frame between the
      development and widespread dissemination of effective methods, thereby reducing
      health cost expenditure.The results of this study will not only inform about the
      degree to which the new methods lead to an improvement of treatment course and
      outcome, but also about whether the effects of routine psychotherapeutic
      treatment are comparable to those of the controlled, strictly manualized
      treatments of the SOPHO-NET study. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT01388231. This study was funded by the German Federal Ministry of
      Education and Research (SOPHO-NET: BMBF 01GV0607; SOPHO-PRAX: BMBF 01GV1001).

PMID- 22647316
TI  - Use of cognitive enhancers for mild cognitive impairment: protocol for a
      systematic review and network meta-analysis.
AB  - BACKGROUND: Elderly individuals who have memory problems without significant
      limitations in activities of daily living are often diagnosed as having mild
      cognitive impairment (MCI). Some of these individuals progress to dementia.
      Several cognitive enhancers (for example donepezil, galantamine, rivastigmine,
      memantine) have been approved for use in people with Alzheimer's dementia but
      their use in patients with MCI is unclear. We aimed to determine the comparative
      effectiveness, safety, and cost of cognitive enhancers for MCI through a
      systematic review and network (that is, indirect comparisons) meta-analysis.
      DESIGN/METHODS: We will include studies that examine the use of cognitive
      enhancers compared to placebo, supportive care, or other cognitive enhancers
      among patients diagnosed with MCI. Outcomes of interest include cognition and
      function (primary outcomes), as well as behavior, quality of life, safety, and
      cost (secondary outcomes). We will include all experimental studies (randomized
      controlled trials, quasi-randomized controlled trials, controlled clinical
      trials), quasi-experimental studies (controlled before-after, interrupted time
      series), and observational studies (cohort, case-control). Studies will be
      included regardless of publication status (that is, we will include unpublished
      studies), year, or language of dissemination.To identify potentially relevant
      material, we will search the following electronic databases from inception
      onwards: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL,
      and Ageline. The electronic database search will be supplemented by scanning the
      reference lists of included studies, searching Google and organization websites
      for unpublished or difficult to locate material literature, and contacting
      experts.Two reviewers will independently screen the studies for inclusion using
      the eligibility criteria established a priori and independently extract data.
      Risk of bias will be assessed using the Cochrane Risk of Bias tool for
      experimental and quasi-experimental studies and the Newcastle Ottawa Scale for
      observational epidemiology studies. Meta-analysis and network meta-analysis are
      planned, if the studies are deemed statistically, methodologically, and
      clinically homogenous. DISCUSSION: Our systematic review will provide important
      information regarding the benefits, costs, and harms of cognitive enhancers for
      patients with MCI. This information can be used to assist healthcare providers,
      policy-makers, MCI patients and their family regarding the use of these agents.
      PROSPERO REGISTRY NUMBER: CRD42012002234.

PMID- 22647317
TI  - Karyotype variations in Italian populations of the peach-potato aphid Myzus
      persicae (Hemiptera: Aphididae).
AB  - In this study, we present cytogenetic data regarding 66 Myzus persicae strains
      collected in different regions of Italy. Together with the most common 2n = 12
      karyotype, the results showed different chromosomal rearrangements: 2n = 12 with
      A1-3 reciprocal translocation, 2n = 13 with A1-3 reciprocal translocation and A3
      fission, 2n = 13 with A3 fission, 2n = 13 with A4 fission, 2n = 14 with X and A3
      fissions. A 2n = 12-13 chromosomal mosaicism has also been observed. Chromosomal
      aberrations (and in particular all strains showing A1-3 reciprocal translocation)
      are especially frequent in strains collected on tobacco plants, and we suggest
      that a clastogenic effect of nicotine, further benefited by the holocentric
      nature of aphid chromosomes, could be at the basis of the observed phenomenon.

PMID- 22647318
TI  - Validation and extension of a simple questionnaire to assess physical activity in
      pre-school children.
AB  - OBJECTIVE: To (i) validate a recently proposed questionnaire tool for the simple
      assessment of physical activity (PA) in pre-school children by comparison with
      accelerometry and heart-rate recordings; and (ii) extend the tool by adding more
      questions to improve validity and to refine the classification from two to three
      categories (PA low, medium, high). SETTING: Baseline data of an intervention
      evaluation study. SUBJECTS: Pre-school children. DESIGN: Children were
      categorized as either physically active or non-active, based on their parents'
      answers to the five-item questionnaire. Activity and heart rate were recorded for
      6 d (Actiheart device; CamNtech, Cambridge, UK). Nightly sleeping periods were
      removed and mean accelerometry counts (MACT), time spent in moderate-to-vigorous
      intensity physical activity (MVPA) and time spent in sedentary behaviour (SB)
      were computed. In a second step, additional questions that improved validity were
      added, resulting in an extended seven-item questionnaire. RESULTS: For 748 (90.4
      %) of the participating children aged 2.3-6.7 years, the questionnaires were
      filled out sufficiently for classification. Children classified as physically
      active showed 9.6 % higher MACT (P < 0.0003), spent more time in MVPA and
      insignificantly less time in SB. Using the extended questionnaire, children with
      PA classified as medium (reference: low) showed 11.0 % more MACT, spent 11.8 %
      more time in MVPA and 4.8 % less time in SB. Children with PA classified as high
      showed 16.9 % more MACT, spent 20.2 % more time in MVPA and 7.2 % less time in
      SB. CONCLUSIONS: With validated PA questionnaires for pre-school children
      lacking, the proposed questionnaire might be a reasonable option to include for
      PA assessment in epidemiological studies where more elaborate measurements are
      unavailable.

PMID- 22647319
TI  - Effect of Ag/Al co-doping method on optically p-type ZnO nanowires synthesized by
      hot-walled pulsed laser deposition.
AB  - Silver and aluminum-co-doped zinc oxide (SAZO) nanowires (NWs) of 1, 3, and 5
      at.% were grown on sapphire substrates. Low-temperature photoluminescence (PL)
      was studied experimentally to investigate the p-type behavior observed by the
      exciton bound to a neutral acceptor (A0X). The A0X was not observed in the 1 at.%
      SAZO NWs by low-temperature PL because 1 at.% SAZO NWs do not have a Ag-O
      chemical bonding as confirmed by XPS measurement. The activation energies (Ea) of
      the A0X were calculated to be about 18.14 and 19.77 meV for 3 and 5 at.% SAZO
      NWs, respectively, which are lower than the activation energy of single Ag-doped
      NW which is about 25 meV. These results indicate that Ag/Al co-doping method is a
      good candidate to make optically p-type ZnO NWs.

PMID- 22647320
TI  - Analysis of active chromatin modifications in early mammalian embryos reveals
      uncoupling of H2A.Z acetylation and H3K36 trimethylation from embryonic genome
      activation.
AB  - Early embryonic development is characterized by dramatic changes in cell potency
      and chromatin organization. The role of histone variants in the context of
      chromatin remodeling during embryogenesis remains under investigated. In
      particular, the nuclear distribution of the histone variant H2A.Z and its
      modifications have not been examined. Here we investigated the dynamics of
      acetylation of H2A.Z and two other active chromatin marks, H3K9ac and H3K36me3,
      throughout murine and bovine pre-implantation development. We show that H2A.Z
      distribution is dynamic during the earliest stages of mouse development, with
      protein levels significantly varying across stages and lowest at the 2-cell
      stage. When present, H2A.Z localizes preferentially to euchromatin at all stages
      analyzed. H2A.Z is acetylated in pre-implantation blastomeres and is
      preferentially localized to euchromatin, in line with the known role of H2A.Zac
      in transcriptional activation. Interestingly, however, H2A.Zac is undetectable in
      mouse embryos at the 2-cell stage, the time of major embryonic genome activation
      (EGA). Similarly, H3K36me3 is present exclusively in the maternal chromatin
      immediately after fertilization but becomes undetectable in interphase nuclei at
      the 2-cell stage, suggesting uncoupling of these active marks with global
      embryonic transcription activation. In bovine embryos, which undergo EGA at the 8
      cell stage, H2A.Zac can be detected in zygotes, 4-, 8- and 16-cell stage embryos
      as well as in blastocysts, indicating that the dynamics of H2A.Zac is not
      conserved in mammals. In contrast, H3K36me3 displays mostly undetectable and
      heterogeneous localization pattern throughout bovine pre-implantation
      development. Thus, our results suggest that 'canonical' active chromatin marks
      exhibit a dynamic behavior in embryonic nuclei, which is both stage- and species
      specific. We hypothesize that chromatin of early embryonic nuclei is subject to
      fine-tuning through differential acquisition of histone marks, allowing for
      proper chromatin remodeling and developmental progression in a species-specific
      fashion.

PMID- 22647322
TI  - Short bowel syndrome presenting with re-feeding syndrome in a Han Chinese
      patient: a case report.
AB  - INTRODUCTION: Re-feeding syndrome is common in patients with long-term
      starvation. To the best of our knowledge this case is the first to report a
      patient with short bowel syndrome developing re-feeding syndrome 12 years after
      the bowel resection. CASE PRESENTATION: A 33-year-old Chinese Han man underwent
      small bowel resection leaving only 40 cm of bowel, without an ileocecal valve, 12
      years previously. At that time he was weaned from total parenteral nutrition and
      had a normal diet. He later developed features of severe malnutrition, and when
      parenteral nutrition was given, he developed re-feeding syndrome. CONCLUSION:
      Although re-feeding syndrome is a common complication in patients with any kind
      of nutritional support, and known to us for many years, high risk patients still
      need more attention and monitoring. Re-feeding syndrome in this case was not only
      a macronutrients deficiency but also a micronutrient deficient, and prompt
      supplement therapy and organ function support proved to be successful.

PMID- 22647323
TI  - [The correlation between the intraoperative flow of coronary artery bypass grafts
      and the patency of grafts at midterm follow-up].
AB  - We evaluated the correlation between the intraoperative flow of coronary artery
      bypass grafting (CABG) and the patency of grafts at midterm follow-up. When
      internal mammary arteries were used as grafts, there was no correlation between
      graft flow rate and graft patency rate. On the other hand, when saphenous vein
      was used, the greater graft flow was associated with better graft patency.
      Receiver operator characteristic( ROC) analysis identified the optimum threshold
      for the intraoperative flow rate to predict the patency at midterm follow-up as
      23 ml/min (sensitivity 78%, specificity 71%). The difference in the correlation(
      of flow rate with patency rate) between the 2 graft types was attributed to the
      difference of physiological reaction of each type of grafts.

PMID- 22647321
TI  - Cognitive behavioural therapy versus multidisciplinary rehabilitation treatment
      for patients with chronic fatigue syndrome: study protocol for a randomised
      controlled trial (FatiGo).
AB  - BACKGROUND: Patients with chronic fatigue syndrome experience extreme fatigue,
      which often leads to substantial limitations of occupational, educational, social
      and personal activities. Currently, there is no consensus regarding the
      treatment. Patients try many different therapies to overcome their fatigue.
      Although there is no consensus, cognitive behavioural therapy is seen as one of
      the most effective treatments. Little is known about multidisciplinary
      rehabilitation treatment, a combination of cognitive behavioural therapy with
      principles of mindfulness, gradual increase of activities, body awareness therapy
      and pacing. The difference in effectiveness and cost-effectiveness between
      multidisciplinary rehabilitation treatment and cognitive behavioural therapy is
      as yet unknown. The FatiGo (Fatigue-Go) trial aims to compare the effects of both
      treatment approaches in outpatient rehabilitation on fatigue severity and quality
      of life in patients with chronic fatigue syndrome. METHODS: One hundred twenty
      patients who meet the criteria of chronic fatigue syndrome, fulfil the inclusion
      criteria and sign the informed consent form will be recruited. Both treatments
      take 6 months to complete. The outcome will be assessed at 6 and 12 months after
      the start of treatment. Two weeks after the start of treatment, expectancy and
      credibility will be measured, and patients will be asked to write down their
      personal goals and score their current performance on these goals on a visual
      analogue scale. At 6 and 14 weeks after the start of treatment, the primary
      outcome and three potential mediators-self-efficacy, causal attributions and
      present-centred attention-awareness-will be measured. Primary outcomes are
      fatigue severity and quality of life. Secondary outcomes are physical activity,
      psychological symptoms, self-efficacy, causal attributions, impact of disease on
      emotional and physical functioning, present-centred attention-awareness, life
      satisfaction, patient personal goals, self-rated improvement and economic costs.
      The primary analysis will be based on intention to treat, and longitudinal
      analysis of covariance will be used to compare treatments. DISCUSSION: The
      results of the trial will provide information on the effects of cognitive
      behavioural therapy and multidisciplinary rehabilitation treatment at 6 and 12
      months follow-up, mediators of the outcome, cost-effectiveness, cost-utility, and
      the influence of treatment expectancy and credibility on the effectiveness of
      both treatments in patients with chronic fatigue syndrome. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN77567702.

PMID- 22647324
TI  - [Initial clinical experience of early cardiac rehabilitation for very elderly
      patients over 85 years old following open heart surgery].
AB  - In this study, we evaluated the initial clinical experience of early cardiac
      rehabilitation( CR) for very elderly patients over 85 years old after open heart
      surgery. From September 2007 to January 2011, 7 consecutive patients (85~90
      years, mean 85.9 years, male:female=4:3) who underwent cardiac surgery in our
      institute were selected. Preoperative activity of daily living (ADL) scores were
      similar in all cases, and 1 patient used a cane for walking. Preoperative New
      York Heart Association (NYHA) classification was class III :3, class IV:4. Three
      patients were admitted for acute congestive heart failure approximately 1 month
      prior to surgery. Standard open heart surgery using bioprosthesis was performed:
      3 patients underwent mitral valve replacement( MVR), 3 had aortic valve
      replacement( AVR), and 1 had tricuspid valve replacement (TVR). Postoperative
      clinical course was uneventful, and the mean time of ventilator support was 12.1
      hours. Thereafter, early CR was introduced at the intensive care unit( ICU) in
      all patients, and the mean time of introduction of early rehabilitation was 1.7
      days. In the last 4 cases, early CR was done the 1st day following surgery. CR
      was effectively performed in all cases without any problems or cardiac events,
      and all patients improved enough to leave their beds at 3~7 days, a mean of 4.4
      days after surgery. The mean hospital stay after surgery was 30.9 days( 23 ~ 42
      days), almost all patients were able to walk independently, and ADL scores at
      discharge were improved. Only 2 patients required a cane for walking.
      Postoperative NYHA classification was improved to class I :5, class II :2. From
      these results, early CR for very elderly patients over 85 years old could be a
      safe and effective tool to improve and maintain the ADL and quality of life
      following surgical intervention.

PMID- 22647325
TI  - [Breast deformities caused by the operation for congenital heart disease].
AB  - Breast deformities are seen as one of the late postoperative complications in
      thoracotomy, but there are very few reports in the literature. We investigated
      causes and treatments in 5 patients who have consulted to our department after
      operations for congenital heart disease between April 1989 and March 2011. The
      injured breast bud in the cardiac operation resulted in hypoplastic deformities,
      and deformities became apparent during puberty with breast growth. These patients
      required release of the scar contracture to lead to normal breast development,
      and also have to been treated chest deformity. After stopping at breast growth in
      adolescence, some augmentations were necessary if bilateral asymmetry had been
      remained. Breast deformities are very important issue in the viewpoints of
      patients' quality of life (QOL), though not relating directly to vital prognosis.
      We'd like to introduce these complications and some choices about breast
      reconstruction to thoracic surgeons.

PMID- 22647326
TI  - [Total port-access robot-assisted lobectomy for lung cancer].
AB  - We reported 2 cases of total port-access right lower lobectomy with hilar and
      mediastinal lymph nodal dissection using the da Vinci surgical system through
      subcostal trans-diaphragmatic approach. In case 1, the operating time was 6 hours
      00 minutes, and the total blood loss was little. In case 2, the operating time
      was 6 hours 30 minutes, and the total blood loss was little. The da Vinci
      surgical system provides a high-resolution stereoscopic image and allows remote,
      tremor-free, and scaled control of endoscopic surgical instruments with 7 degrees
      of freedom. Minimally invasive robot-assisted lobectomy is an effective procedure
      and may add benefits for both surgeon and patients.

PMID- 22647327
TI  - [Leiomyosarcoma of pulmonary artery origin diagnosed preoperatively].
AB  - A 59-year-old woman was pointed out isotope uptake at the right pulmonary hilum
      by positron emission tomography/computed tomography (PET/CT) performed for
      postoperative follow up of thyroid cancer. Chest enhanced CT showed a mass in the
      right pulmonary artery, which was diagnosed as sarcoma of pulmonary artery origin
      by a transcatheter biopsy. Chemotherapy by doxorubicin with anticoagulation
      therapy was started 1st due to the secondary pulmonary hypertension. Pulmonary
      hypertension was improved, but the size of the tumor enlarged. She underwent
      right pneumonectomy with mediastinal dissection. The tumor was completely
      resected, but brain metastases developed. Postoperative pathological diagnosis
      was leiomyosarcoma. A rare case of preoperatively diagnosed pulmonary arterial
      sarcoma was reported.

PMID- 22647328
TI  - [Thymic carcinoid associated with multiple endocrine neoplasia type 1].
AB  - We report a case of a thymic carcinoid associated with multiple endocrine
      neoplasia type 1( MEN-1). A 37-year-old man was referred to our hospital for
      further examination of an abnormal chest shadow. A chest computed tomography (CT)
      showed an anterior mediastinal mass measuring 6.5 cm in diameter. A pathological
      diagnosis of thymic carcinoid was made from a CT-guided needle biopsy specimen.
      Preoperative workup including endocrinological examination revealed a pituitary
      adenoma and hyperparathyroidism, and MEN-1 was clinically diagnosed. We performed
      total parathyroidectomy with autotransplantation and thymectomy with lymph node
      dissection through cervical collar incision and median sternotomy. The diagnosis
      of MEN-1 was confirmed by the genomic analysis postoperatively. Since 25% of
      thymic carcinoids are MEN-1 related and 95% of MEN-1 patients develop
      hyperparathyroidism, it should be kept in mind that this condition can be treated
      by thymectomy and concurrent parathyroidectomy.

PMID- 22647329
TI  - [Acute aortic dissection with anomalous coronary artery].
AB  - A 38-year-old man was diagnosed with acute type A aortic dissection and severe
      aortic regurgitation, and taken immediately to the operating room for repair of
      the ascending aorta using the Bentall procedure. The presence of the anomalous
      right coronary artery was revealed at the time of the procedure, and was repaired
      with single coronary button technique. Some case reports have described anomalous
      coronary artery in association with acute myocardiac infarction or angina
      pectoris. This report describes a case of anomalous coronary artery diagnosed
      during an emergency operation for aortic dissection.

PMID- 22647330
TI  - [Combined valve surgery in end-stage renal disease patient with porcelain aorta
      and mitral annulus calcification].
AB  - A 66-year-old woman, who had been receiving regular hemodialysis for 11 years,
      was referred to our hospital because of heart failure due to combined valve
      disease complicated by porcelain aorta and mitral annulus calcification. We
      performed ascending aortic replacement under hypothermic arrest, and double valve
      replacement and tricuspid valve annuloplasty during rewarming. It was noted that
      the annulus of P3 of mitral valve had been replaced with atherosclerotic plaque
      containing calcification. We did not perform debridement. We placed non-everted
      horizontal mattress sutures from the left ventricle to the atrium on the anterior
      annulus and P1 to P2 annulus, and everted horizontal mattress sutures on the left
      atrial wall close to the calcified P3 annulus. Then, we successfully replaced the
      mitral valve with a 23-mm St. Jude Medical valve in a supra-annular position. The
      patient was discharged from the hospital 44 days after the operation.

PMID- 22647331
TI  - [Prosthetic valve re-replacement one year after the surgery using a mosaic
      bioprosthesis].
AB  - A 69-year-old man underwent aortic valve replacement with a 21 mm-Mosaic
      bioprosthetic valve for the treatment of aortic valve stenosis and resulting
      syncope. One year after the 1st operation, syncope recurred. Echocardiography
      showed non-symmetrical enlargement( ASH) of the ventricular septum as well as
      turbulence and increase of the pressure gradient in the left ventricular outlet.
      Prosthetic valve dysfunction was diagnosed. At the 2nd operation, tears on 2
      coronary cusps of the bioprosthetic valve and a subvalvular overgrown pannus were
      revealed. Aortic valve re-replacement with a 19 mm-SJM Regent valve and the
      Morrow operation were performed. On analysis of the explanted bioprothesis,
      distortion of the valvular stent was found. We speculated that distortion of the
      bioprosthetic stent due to ASH caused the contact of the stent-post and the
      valvular leaflets, and 2 tears of the leaflets occurred. Pannus formation was
      thought to have resulted from the fast turbulence caused by ASH and the
      distortion of the stent.

PMID- 22647332
TI  - [Cardiac angiosarcoma resected after definitive diagnosis by thoracoscope
      assisted biopsy].
AB  - A 31-year-old woman presented with cardiac tamponade. Contrast-enhanced chest
      computed tomography(CT) revealed an inhomogeneously-enhanced soft tissue mass
      measuring 50*35*30 mm, which was in contact with the right atrial wall. The mass
      was definitely diagnosed as cardiac angiosarcoma by thoracoscope-assisted biopsy.
      The right atrial wall, including the tumor, was extensively resected, and then
      reconstructed with the equine pericardium. Postoperative radiation therapy was
      performed, but the patient developed malignant ascites with an intra-pericardial
      ectopic tumor recurrence. Additional radiation therapy was performed, but she
      died 177 days after the operation. Although thoracoscopeassisted biopsy is
      considered to be a useful diagnostic method for cardiac tumors on the surface of
      the heart, it carries the risk of spreading tumor cells. In the present case, the
      tumor should have been resected immediately after the prompt pathological
      diagnosis.

PMID- 22647333
TI  - [Thymic carcinoma with vascular resection].
AB  - Thymic carcinomas are rare neplasm. The standard treatment for advanced thymic
      carcinoma has not yet been established, and the prognosis is poor. We report 3
      cases of thymic carcinoma involving major vessely. Case 1:The aortic arch and the
      innominate vein were involved. Case 2:The left brachiocephalic vein was involved.
      Case 3:Tumor invaded to superior vena cava. Complete resection of the tumor was
      possible with vascular reconstruction.

PMID- 22647334
TI  - [Pulmonary cryptococcosis preoperatively diagnosed as lung cancer].
AB  - A 60-year-old woman was referred to our hospital with an abnormal shadow on chest
      radiography. Chest computed tomography( CT) showed a nodular shadow 1 cm in
      diameter with spiculation at S6a of the right inferior lobe. The patient was
      diagnosed as having a class V squamous cell carcinoma by bronchoscopic
      exfoliative cytology and was thus hospitalized for surgery. The nodule was
      resected by partial resection of the lung for intraoperative rapid pathology.
      Since the diagnosis was an inflammatory node, further procedure was not
      performed. Histopathological examination of the permanent specimen revealed a
      diagnosis of pulmonary cryptococcosis.

PMID- 22647335
TI  - [Bioprosthetic valve endocarditis associated with rapid progression of valvular
      stenosis;report of a case].
AB  - Long-term durability and stability of the hemodynamic performance of commercially
      available 2nd generation Carpentier-Edwards stented bovine pericardial aortic
      bioprostheses (Perimount valve) is reported based on echocardiographic follow-up
      examinations. Prosthetic valve deterioration of the Perimount valve usually
      occurs late and is age-dependent. We describe bioprosthetic valve deterioration
      of a Perimount valve with severe stenotic change 1 month postoperatively that
      developed in an infective endocarditis patient. Although preoperative
      echocardiography showed no signs of valve dehiscence or vegetation on the
      prosthesis, valve stenosis alone had progressed extremely rapidly during 2 weeks
      of febrile symptom. The valve leaflet was found at explant to be infiltrated with
      a cellular material fibrin other than bacteria or leukocytes. This rare
      occurrence needs to be reported in the literature to forewarn clinicians of an
      early manifestation of endocarditis that may not be recognized yet.

PMID- 22647336
TI  - [Aortic arch and valve replacement in a hemodialysis patient with a porcelain
      aorta;report of a case].
AB  - We report a case of thoracic aortic aneurysm and aortic valve stenosis with
      chronic renal failure requiring hemodialysis. A 75-year-old man complained of
      back pain and hoarseness. He had been on dialysis for 15 years. A computed
      tomography scan of the chest showed marked calcification in the thoracic aortic
      arch, which is known as a porcelain aorta, and a distal arch aneurysm.
      Echocardiographic examination showed moderate aortic valve stenosis with
      calcification. An operation was scheduled, and both the aortic valve and the
      aortic arch aneurysm were successfully replaced with a mechanical valve and a
      prosthetic graft. Cardiovascular surgery for patients complicated by a porcelain
      aorta requires extra cares for the establishment of cardiopulmonary bypass and
      anastomoses of the aorta.

PMID- 22647337
TI  - [Mediastinal lymph node carcinoma of unknown primary site; report of a case].
AB  - A 71-year-old woman was admitted to our hospital because of a mediastinal mass.
      Chest computed tomography (CT) and fluorodeoxyglucose-positron emission
      tomography (FDG-PET) showed only 1 swollen mediastinal lymph node. Serum levels
      of carcinoembryonic antigen (CEA) were found to be elevated. Preoperative
      examination did not detect the primary lesion. A mediastinal lymphadenectomy was
      performed, and histologically, the tumor demonstrated poorly differentiated
      adenocarcinoma. Immunohistochemical staining for cytokine( CK) 7 and thyroid
      transcription factor( TTF) -1 were positive but were negative for CK20,
      suggesting a pulmonary origin. During 2-years postoperative follow-up, no signs
      of primary site growth can be detected. Surgical resection of mediastinal lymph
      node carcinoma of unknown primary site has the possibility of a good prognosis.

PMID- 22647338
TI  - [Mediastinal cystic lymphangioma; report of a case].
AB  - A cystic lymphangioma is a rare mediastinal benign tumor. A 38-year-old male was
      referred to our hospital because of an mediastinal mass incidentally detected on
      chest X-ray. The mass had enlarged rapidly during the course of 1 year. Computed
      tomography (CT) of the chest showed a 7 cm well defined cystic tumor in the left
      anterior mediastinum. Magnetic resonance imaging (MRI) demonstrated a mass with
      heterogeneous high signal intensity on enhanced T2-weighted images. The cystic
      tumor, localized in the mediastinal adipose tissue, was completely resected by a
      thoracoscopic procedure. A pathological examination confirmed the diagnosis of a
      cystic lymphangioma.

PMID- 22647339
TI  - [Benign metastasizing leiomyoma; report of a case].
AB  - We report very rare case of benign mestasizing leiomyoma (BML). A 42-year-old
      female was referred to our hospital presenting with abnormal shadows revealed by
      a chest X-ray film. Chest computed tomography (CT) scan revealed multiple well
      defined nodules in bilateral lung field, suggesting metastatic lung tumor.
      Further examination could not detect any suspicious primary lesion. Several tumor
      markers were all within normal limits. Surgical resection was performed to
      establish diagnosis and treatment. Pathological diagnosis was BML from the uterus
      myoma which had been resected 5 years before.

PMID- 22647340
TI  - Urea for treatment of acute SIADH in patients with subarachnoid hemorrhage: a
      single-center experience.
AB  - BACKGROUND: Hyponatremia occurring as a result of the syndrome of inappropriate
      antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome is a
      common complication in patients with subarachnoid hemorrhage (SAH). The efficacy
      and safety of urea as treatment for SIADH-induced hyponatremia has not been
      reported in this population. METHODS: This is a retrospective analysis of all
      patients admitted to our department for nontraumatic SAH between January 2003 and
      December 2008 (n = 368). All patients with SIADH-induced hyponatremia (plasma
      sodium < 135 mEq/L, urine sodium > 20 mEq/L, and osmolality > 200 mOsm/kg;
      absence of overt dehydration or hypovolemia; no peripheral edema or renal
      failure; no history of adrenal or thyroid disease) routinely received urea per os
      when hyponatremia was associated with clinical deterioration or remained less
      than 130 mEq/L despite saline solution administration. RESULTS: Forty-two
      patients developed SIADH and were treated with urea. Urea was started after a
      median of 7 (IQR, 5-10) days and given orally at doses of 15-30 g tid or qid for
      a median of 5 (IQR, 3-7) days. The median plasma sodium increase over the first
      day of treatment was 3 (IQR, 1-6) mEq/L. Hyponatremia was corrected in all
      patients, with median times to Na+ >130 and >135 mEq/L of 1 (IQR, 1-2) and 3
      (IQR, 2-4) days, respectively. Urea was well tolerated, and no adverse effects
      were reported. CONCLUSIONS: Oral urea is an effective and well-tolerated
      treatment for SIADH-induced hyponatremia in SAH patients.

PMID- 22647341
TI  - Oviposition strategies of temporary pool mosquitoes in relation to weather, tidal
      regime and land use in a temperate wetland.
AB  - Wetlands have traditionally been associated with harbouring mosquitoes, a well
      known nuisance and vectors of diseases. Within mosquito life cycle, oviposition
      is a determinant event by shaping their individual fitness and vectorial
      capacity. The study was conducted in one of the main temperate wetlands in South
      America. We used Generalized Linear Models to study the relation between
      temperature, precipitation, tidal regime, land use, microenvironment, and the
      occurrence of floodwater (Ochlerotatus and Psorophora spp.) and raft-laying
      (Culex and Uranotaenia spp.) mosquitoes using temporary pools as larval habitats.
      Pool occurrence was negatively associated with temperature, and positively
      related to precipitation and high tides. As regards the land use, it was lowest
      in domestic areas and plantations, intermediate in secondary forests, and highest
      in marshes. Each oviposition strategy was best modelled as a function of
      different environmental factors. The occurrence of floodwater mosquitoes was
      positively associated with high cumulative precipitation and low tide records.
      Raft-laying mosquitoes were related to low temperature records, while the effect
      of flooding varied with the land use. In view of these results, physical (water
      inputs and movement), chemical, and biological (egg and larval flushing, and
      predatory interactions) considerations are given to provide insight in the
      oviposition patterns of mosquitoes occurring in this complex wetland. We finally
      propose the generation of a tidal flow as a control measure against floodwater
      mosquitoes, which are the most anthropophilic in the study area.

PMID- 22647342
TI  - Evidence on the prevalence and geographic distribution of major cardiovascular
      risk factors in Italy.
AB  - OBJECTIVE: To assess the prevalence and geographic distribution of major
      cardiovascular risk factors in a large community-wide sample of the Italian
      population. DESIGN: A cross-sectional survey. Standardized methods were used to
      collect and measure cardiovascular risk factors. Data were adjusted for survey
      weightings. Qualitative and quantitative variables were compared with parametric
      and non-parametric tests, as appropriate. SETTING: Towns (n 193) across different
      Italian regions. SUBJECTS: Unselected adults (n 24 213; 12 626 men; 11 587 women)
      aged 18-98 years (mean age 56.9 (sd 15.3) years), who volunteered to participate
      in a community-wide screening programme over a 2 d period in 2007. RESULTS:
      Overall, the prevalence of major cardiovascular risk factors was: obesity, 22.7 %
      (women 18.9 %, men 26.1 %); overweight, 44.7 % (women 31.6 %, men 56.7 %);
      hypertension, 59.6 % (women 48.3 %, men 70.0 %); dyslipidaemia, 59.1 % (women
      57.7 %, men 60.3 %); diabetes, 15.3 % (women 11.2 %, men 19.0 %) and smoking,
      19.8 % (women 14.0 %, men 25.2 %). We found a high prevalence of unhealthy eating
      habits; fruit and vegetable consumption was below the recommended range in 60 %
      of the study population. Ninety per cent of the study population had more than
      one cardiovascular risk factor and 84 % had between two and five cardiovascular
      risk factors. There were differences among Italian macro-areas mainly for
      obesity, hypertension, dyslipidaemia and diabetes. CONCLUSIONS: The study
      provides alarming evidence on current prevalence data for major cardiovascular
      risk factors in a large sample of the Italian population. Particularly, obesity
      and hypertension represent a relevant public health problem. There is a pressing
      need for effective preventive health measures which must also take into account
      the differences among Italian macro-areas.

PMID- 22647343
TI  - Effects of acidity on the size of polyaniline-poly(sodium 4-styrenesulfonate)
      composite particles and the stability of corresponding colloids in water.
AB  - The practical application of polyaniline-poly(sodium 4-styrenesulfonate) (PANI
      PSS) composite particles has been held back by the low stability of their
      dispersed state in water. In this work, we present a general oxidation approach
      to prepare PANI-PSS composite nanoparticles that can form highly stable colloids
      in water or buffer over a wide range of pH from 1 to 11. We demonstrate that the
      size of the PANI-PSS composite particles can be controlled by the acidity of
      precursor solutions. It is hypothesized that the number of negatively charged
      sites on PSS, which can be affected by the acidity of the precursor solutions,
      plays an important role in determining the size of the PANI-PSS composite
      particles and the stability of corresponding colloids in water.

PMID- 22647344
TI  - Micelle to vesicle transitions of N-dodecyl-1, omega-diaminoalkanes: effects of
      pH, temperature and salt.
AB  - The self-assembly behavior of pH-sensitive amphiphiles N-dodecyl-1, 2
      diaminoethane (C12N2N), N-dodecyl-1, 3-diaminopropane (C12N3N) and N-dodecyl-1, 4
      diaminobutane (C12N4N) has been studied in aqueous solutions. Light scattering,
      viscosity and cryo-transmission electronic microscopy (cryo-TEM) results revealed
      that the aggregates transferred from spherical micelles to vesicles (MVT) via
      wormlike micelles as the pH was gradually varied from acidic to basic conditions.
      pH-dependent zeta potential and (1)H NMR studies confirmed these transitions.
      Interestingly, the formed wormlike micelles could transform into vesicles upon
      heating, which was studied by cryo-TEM, light scattering and viscosity techniques
      in detail. It is concluded that the pH and thermal MVT are a general phenomenon
      in all three amphiphiles investigated. Furthermore, NaCl induced a wormlike
      micelle to vesicle transition was also observed in C12N2N solution.

PMID- 22647345
TI  - Quasi-classical modeling of molecular quantum-dot cellular automata multidriver
      gates.
AB  - Molecular quantum-dot cellular automata (mQCA) has received considerable
      attention in nanoscience. Unlike the current-based molecular switches, where the
      digital data is represented by the on/off states of the switches, in mQCA
      devices, binary information is encoded in charge configuration within molecular
      redox centers. The mQCA paradigm allows high device density and ultra-low power
      consumption. Digital mQCA gates are the building blocks of circuits in this
      paradigm. Design and analysis of these gates require quantum chemical
      calculations, which are demanding in computer time and memory. Therefore,
      developing simple models to probe mQCA gates is of paramount importance. We
      derive a semi-classical model to study the steady-state output polarization of
      mQCA multidriver gates, directly from the two-state approximation in electron
      transfer theory. The accuracy and validity of this model are analyzed using full
      quantum chemistry calculations. A complete set of logic gates, including
      inverters and minority voters, are implemented to provide an appropriate test
      bench in the two-dot mQCA regime. We also briefly discuss how the QCADesigner
      tool could find its application in simulation of mQCA devices.

PMID- 22647346
TI  - Dreaming without REM sleep.
AB  - To test whether mental activities collected from non-REM sleep are influenced by
      REM sleep, we suppressed REM sleep using clomipramine 50mg (an antidepressant) or
      placebo in the evening, in a double blind cross-over design, in 11 healthy young
      men. Subjects were awakened every hour and asked about their mental activity. The
      marked (81%, range 39-98%) REM-sleep suppression induced by clomipramine did not
      substantially affect any aspects of dream recall (report length, complexity,
      bizarreness, pleasantness and self-perception of dream or thought-like
      mentation). Since long, complex and bizarre dreams persist even after suppressing
      REM sleep either partially or totally, it suggests that the generation of mental
      activity during sleep is independent of sleep stage.

PMID- 22647347
TI  - Stereotactic conformal radiotherapy in non-small cell lung cancer - an overview.
AB  - Stereotactic conformal radiotherapy is an established technique in treating
      cranial lesions and has made significant inroads in the treatment of extracranial
      sites as well. Early stage non-small cell lung cancer is one such site. This
      overview assesses the results that have been achieved with stereotactic conformal
      radiotherapy in non-small cell lung cancer so far and compares its efficacy with
      surgical and other non-surgical modalities.

PMID- 22647348
TI  - [Cerebral lesions].

PMID- 22647349
TI  - Automated image analysis of cyclin D1 protein expression in invasive lobular
      breast carcinoma provides independent prognostic information.
AB  - The emergence of automated image analysis algorithms has aided the enumeration,
      quantification, and immunohistochemical analyses of tumor cells in both whole
      section and tissue microarray samples. To date, the focus of such algorithms in
      the breast cancer setting has been on traditional markers in the common invasive
      ductal carcinoma subtype. Here, we aimed to optimize and validate an automated
      analysis of the cell cycle regulator cyclin D1 in a large collection of invasive
      lobular carcinoma and relate its expression to clinicopathologic data. The image
      analysis algorithm was trained to optimally match manual scoring of cyclin D1
      protein expression in a subset of invasive lobular carcinoma tissue microarray
      cores. The algorithm was capable of distinguishing cyclin D1-positive cells and
      illustrated high correlation with traditional manual scoring (kappa=0.63). It was
      then applied to our entire cohort of 483 patients, with subsequent statistical
      comparisons to clinical data. We found no correlation between cyclin D1
      expression and tumor size, grade, and lymph node status. However, overexpression
      of the protein was associated with reduced recurrence-free survival (P=.029), as
      was positive nodal status (P<.001) in patients with invasive lobular carcinoma.
      Finally, high cyclin D1 expression was associated with increased hazard ratio in
      multivariate analysis (hazard ratio, 1.75; 95% confidence interval, 1.05-2.89).
      In conclusion, we describe an image analysis algorithm capable of reliably
      analyzing cyclin D1 staining in invasive lobular carcinoma and have linked
      overexpression of the protein to increased recurrence risk. Our findings support
      the use of cyclin D1 as a clinically informative biomarker for invasive lobular
      breast cancer.

PMID- 22647350
TI  - Pathologic significance of immunoglobulin G4-positive plasma cells in
      extrahepatic cholangiocarcinoma.
AB  - Immunoglobulin G4-related sclerosing cholangitis is histologically characterized
      by the infiltration of immunoglobulin G4-positive plasma cells and sclerosing
      change. Moreover, several cases of carcinoma accompanied by immunoglobulin G4
      positive cells in tissue and increased serum immunoglobulin G4 levels have been
      reported, but the association between cancer-associated immunity and an
      immunoglobulin G4 reaction is still unclear. In this study, we examined the
      infiltration of immunoglobulin G4-positive cells in extrahepatic
      cholangiocarcinoma and the pathologic significance of the immunoglobulin G4
      reaction found in cancer tissues in terms of the evasion of immune surveillance
      by regulatory T cells. Immunohistochemistry for immunoglobulin G4, forkhead box
      P3, CD4, and CD8 was performed using 68 surgical specimens from patients with
      extrahepatic cholangiocarcinoma, and positive cells were investigated,
      particularly within and around cancerous tissues. Consequently, although
      immunoglobulin G4+ cells were few (average, <10 cells/high-power field) in most
      cases, 10 or more and 50 or more cells were found in 37% and 6% of cases,
      respectively. Immunoglobulin G4+ cells were predominantly found in the invasive
      front of carcinoma tissue. In the cases with 10 or more immunoglobulin G4+ cells,
      forkhead box P3+ regulatory T cells were also distinguishable, and a positive
      correlation was found between the forkhead box P3+/CD4+ ratio and immunoglobulin
      G4+ cell count, but few CD8+ cells invaded cancer cells (<10 cells). In
      conclusion, extrahepatic cholangiocarcinomas are often accompanied by the
      significant infiltration of immunoglobulin G4+ cells, and the immunoglobulin G4
      reaction showed a positive and negative correlation with forkhead box P3+ and
      CD8+ cells, respectively, suggesting the evasion of immune surveillance
      associated with CD8+ cytotoxic T cells via the regulatory function of forkhead
      box P3+ regulatory T cells.

PMID- 22647351
TI  - Argonaute, Dicer, and Drosha are up-regulated along tumor progression in serous
      ovarian carcinoma.
AB  - MicroRNAs are posttranscriptional regulators of messenger RNA synthesis that are
      intracellularly processed and transferred by the microRNA-regulating machinery
      consisting of Drosha, Dicer, and Argonaute. The present study analyzed the
      expression and clinical role of the microRNA-regulating machinery in advanced
      stage ovarian carcinoma. Drosha, Dicer, Argonaute 1, and Argonaute 2 messenger
      RNA levels were analyzed in 144 specimens (82 effusions, 33 primary carcinomas,
      and 29 solid metastases) using quantitative polymerase chain reaction. Dicer,
      Argonaute 1, and Argonaute 2 protein levels were analyzed in 103 of the above
      specimens by Western blotting. Argonaute 1, Argonaute 2, and Drosha messenger
      RNAs were overexpressed in effusions compared with primary carcinomas and solid
      metastases (P<.001), whereas Argonaute 1 protein expression was highest in solid
      metastases (P=.004). Significantly higher expression of all 4 messenger RNAs was
      found in effusions compared with primary carcinomas (P<.001 to P=.006), whereas
      Argonaute 2 messenger RNA (P=.002), Drosha messenger RNA (P=.009), and Dicer
      protein (P=.006) were overexpressed in solid metastases compared with primary
      carcinomas. Drosha, Dicer, Argonaute 1, and Argonaute 2 messenger RNAs and
      protein levels in effusions were unrelated to clinicopathologic parameters. In
      primary carcinomas, higher levels of 3 messenger RNAs were significantly
      associated with high-grade histology (P=.003 for Dicer and P=.01 for Drosha and
      Argonaute 1). Higher Argonaute 2 messenger RNA levels in prechemotherapy
      effusions were related to shorter progression-free survival (P=.049), a finding
      that retained its significance in multivariate Cox analysis (P=.046). In
      conclusion, Drosha, Dicer, Argonaute 1, and Argonaute 2 are differentially
      expressed at different metastatic sites in ovarian carcinoma compared with
      primary carcinomas, suggesting a role for these molecules in tumor progression.
      Their clinical role in metastatic ovarian carcinoma merits further research.

PMID- 22647353
TI  - Therapeutic targets and recent advances in protein immunotoxins.
AB  - Targeted therapy has replaced the conventional methods of disease management with
      the advances in recombinant technology and increased understanding of molecular
      mechanisms of diseases. The immunotoxin strategy for diseases like cancer and a
      variety of autoimmune disorders has been used successfully in the past since its
      discovery. Since bacterial, fungal and plant toxins have various limitations like
      toxicity and immunogenicity, studies on fully humanized immunotoxins have gained
      attraction recently, which reduced toxicity significantly. Improved methods of
      antibody engineering have led to the emergence of various new formats of
      immunotoxins. This review summarizes the target moieties used in immunotoxin
      constructs in different diseases and describes the recent advances in immunotoxin
      targeting.

PMID- 22647352
TI  - Glomerulitis and endothelial cell enlargement in C4d+ and C4d- acute rejections
      of renal transplant patients.
AB  - In acute rejection after renal transplant, glomerulitis is characterized by
      mononuclear cells in glomerular capillaries and endothelial cell enlargement. In
      association with C4d deposition in peritubular capillaries, glomerulitis is a
      feature of acute antibody-mediated rejection. Prognosis in C4d(+) rejection is
      poorer than in C4d(-) rejection. We measured the glomerular endothelial cell area
      in C4d(+) and C4d(-) acute rejections by morphometry. In 90 acute rejection
      biopsies, glomerulitis was present in 36 cases (group G) and absent in 54 (group
      G0). In biopsies without rejections and in C4d(-) biopsies of group G0,
      glomerular endothelial cell area was not significantly different. In C4d(-) and
      C4d(+) biopsies of group G, the area in inflamed glomeruli was greater than that
      in C4d(-) biopsies of group G0 (P < .02 and P < .006, respectively). In C4d(+)
      biopsies of group G0, it was, unexpectedly, greater than in C4d(-) biopsies of
      group G (P < .01). Circulating posttransplant anti-human leukocyte antigen class
      I and class II antibodies correlated with increased endothelial cell area (P <
      .02). Glomerulitis was associated with diffuse C4d deposition (odds ratio [OR],
      4.27; P < .004); C4d deposition was associated with steroid resistance (OR, 4.97;
      P < .002). Only in C4d(+) rejections did the presence of glomerulitis increase
      this association (OR, 9.17; P < .02). In conclusion, we quantified an increase of
      endothelial cell area in glomerulitis of C4d(+) and C4d(-) acute rejections
      (group G). An increase of this area in C4d(+) biopsies without glomerulitis
      (group G0) suggests complement-mediated damage in the absence of mononuclear cell
      margination.

PMID- 22647354
TI  - The autophagy community.
AB  - There are various definitions of community. A definition that I found in one of
      my dictionaries is the following: "A social, religious, occupational, or other
      group sharing common characteristics or interests and perceived or perceiving
      itself as distinct in some respect from the larger society within which it
      exists." Thus, I think it is fair to say that there is a worldwide autophagy
      community. That is, there is a group of researchers (our occupation), whose
      members share an interest in autophagy (our common characteristic), and that
      group is distinct from the larger society (I do not want to begin describing the
      many ways this applies). But do we feel like a community, and do we need a
      community? I suggest that a community is indeed beneficial, and I propose one
      mechanism for enhancing the development of the autophagy community.

PMID- 22647355
TI  - Facklamia sourekii necrotizing gangrene.

PMID- 22647356
TI  - Introduction to the role of microRNAs in cancer diagnosis, prognosis, and
      treatment.

PMID- 22647357
TI  - Causes and consequences of microRNA dysregulation.
AB  - It is currently well recognized that microRNA deregulation is a hallmark of human
      cancer, and an aberrant expression of these tiny regulatory RNA molecules in
      several cell types is not just a random association, but it also plays a causal
      role in different steps of the tumorigenic process, from the initiation and
      development to progression toward the acquisition of a metastatic phenotype.
      Different regulatory mechanisms can control microRNA expression at a genetic or
      epigenetic level as well as involve the biogenesis machinery or the recruitment
      of specific transcription factors. The tumorigenic process implies a substantial
      alteration of these mechanisms, thus disrupting the equilibrium within the cell
      and leading to a global change in microRNA expression, with loss of
      oncosuppressor microRNAs and overexpression of oncomiRNAs. We review the main
      mechanisms regulating microRNAs and the consequences of their aberrant expression
      in cancer, with a glance at the possible implications at a clinical point of
      view.

PMID- 22647358
TI  - Cross talk between microRNA and coding cancer genes.
AB  - MicroRNAs (miRNAs) are a class of noncoding RNAs (ncRNAs) and posttranscriptional
      gene regulators shown to be involved in pathogenesis of all types of human
      cancers. Their aberrant expression as tumor suppressors can lead to
      cancerogenesis by inhibiting malignant potential, or when acting as oncogenes, by
      activating malignant potential. Differential expression of miRNA genes in
      tumorous tissues can occur owing to several factors including positional effects
      when mapping to cancer-associated genomic regions, epigenetic mechanisms, and
      malfunctioning of the miRNA processing machinery, all of which can contribute to
      a complex miRNA-mediated gene network misregulation. They may increase or
      decrease expression of protein-coding genes, can target 3'-UTR or other genic
      regions (5'-UTR, promoter, coding sequences), and can function in various
      subcellular compartments, developmental, and metabolic processes. Because
      expanding research on miRNA-cancer associations has already produced large
      amounts of data, our main objective here was to summarize main findings and
      critically examine the intricate network connecting the miRNAs and coding genes
      in regulatory mechanisms and their function and phenotypic consequences for
      cancer. By examining such interactions, we aimed to gain insights for the
      development of new diagnostic markers as well as identification of potential
      venues for more selective tumor therapy. To enable efficient examination of the
      main past and current miRNA discoveries, we developed a Web-based miRNA timeline
      tool that will be regularly updated (http://www.integratomics
      time.com/miRNA_timeline). Further development of this tool will be directed at
      providing additional analyses to clarify complex network interactions between
      miRNAs, other classes of ncRNAs, and protein-coding genes and their involvement
      in development of diseases including cancer. This tool therefore provides curated
      relevant information about the miRNA basic research and therapeutic application
      all at hand on one site to help researchers and clinicians in making informed
      decision about their miRNA cancer-related research or clinical practice.

PMID- 22647360
TI  - MicroRNA expression signatures in solid malignancies.
AB  - An ongoing challenge in cancer research is represented by the identification of
      new specific clinical molecular markers and pharmacological targets. During the
      last 10 years, microRNAs (miRNAs) have become one of the hottest subjects in the
      area of cancer genomics. MicroRNAs are single-stranded RNAs of 19 to 24
      nucleotides in length generated through a complex maturation process. Recent
      studies have demonstrated that microRNAs can have an oncogene or tumor suppressor
      role by regulating the expression of target genes. Therefore, microRNAs are
      highly related to cancer processes, including initiation, growth, apoptosis,
      invasion, and metastasis. In this panorama, several high-through put technologies
      studies have revealed miRNA roles in classifying tumors and predicting patient
      outcome with high accuracy. We provide a review highlighting recent progress on
      the understanding of the cellular function of human microRNAs and their
      expression in solid tumors.

PMID- 22647359
TI  - The duality of oncomiR addiction in the maintenance and treatment of cancer.
AB  - It has long been established that cancers can become addicted to particular
      oncogenes. Despite the genetic complexity that governs tumorigenesis, certain
      cancers can exhibit a critical dependency on the expression of a single oncogene,
      which when removed leads to death of the cancer cell. Recent observations on the
      relationships between regulatory RNAs and cancer have revealed that this concept
      of oncogene addiction extends to microRNAs (miRNAs) as well. Certain cancers
      exhibit a dependency on the expression of a single oncogenic miRNA, or oncomiR.
      The field of miRNA biology and its involvement in diseases such as cancer have
      seen tremendous advances over the past decade. However, little is known about the
      phenomenon of oncomiR addiction. In this review, we introduce the concept of
      proto-oncomiRs, or miRNAs that gain oncogenic activity after an initiating event.
      Furthermore, by highlighting the role of proto-oncomiRs in generating malignant
      phenotypes, we glean possible insights into the mechanisms that guide oncomiR
      addiction. In addition, toward the realization of genetically driven personalized
      medicine, some of the most clinically successful anticancer strategies have
      involved targeting addictive oncogenes such as HER2, BCR/ABL, EGFR, and VEGF.
      Elucidating how addictive miRNAs can perpetuate cancer may reveal additional
      critical molecular targets to exploit for therapeutic purposes. Therefore, in
      this review, we also summarize the field of anti-miRNA therapeutics, in which
      antisense and nanoscale delivery technologies are the driving force. Addictive
      oncomiRs are a double-edged sword; addicted cancers are dependent on oncomiRs
      that are highly potent therapeutic targets. Dissection of this phenomenon may
      reveal the mechanisms through which lynchpin miRNAs can perpetuate cancer and
      present a new paradigm for miRNA-based cancer therapy.

PMID- 22647362
TI  - MicroRNAs and prostate cancer: from preclinical research to translational
      oncology.
AB  - The management of prostate cancer patients is rapidly changing. The extended
      survival seen in randomized phase III trials with new molecules has significantly
      enriched the therapeutic armamentarium, and ongoing clinical trials are assessing
      whether the integration of these active drugs within established therapeutic
      regimens results in a further benefit for patients. This complex scenario is
      raising the need for the identification and validation of biomarkers able to
      drive the decision-making process during the course of the disease. Compelling
      evidence has documented the role of microRNAs in cancer biology, and their
      multifaceted biological activity makes them an attractive candidate as
      diagnostic, prognostic, and predictive biomarkers. This review summarizes the
      current knowledge about microRNA deregulation in prostate cancer, how these
      molecules have been investigated in the clinical setting, and strategies
      investigators should consider for sharpening their potential.

PMID- 22647361
TI  - The role of microRNAs in colorectal cancer.
AB  - During the last decade, it has become clear that aberrant microRNA expression has
      a functional role in the initiation and progression of colorectal cancer (CRC).
      Specific microRNAs can act as either tumor suppressors or oncogenes depending on
      the cellular environment in which they are expressed. The expression of microRNAs
      is reproducibly altered in CRC, and their expression patterns are associated with
      diagnosis, prognosis, and therapeutic outcome in CRC. Studies have begun to
      examine the association of microRNA-related polymorphisms and their association
      with CRC incidence and prognosis as well as the possibility of using circulating
      microRNAs or fecal microRNA expression as noninvasive early detection biomarkers.
      These data suggest that microRNAs may be potential molecular classifiers, early
      detection biomarkers, and therapeutic targets for CRC. Here, we will review the
      evidence demonstrating a role of microRNAs in CRC.

PMID- 22647364
TI  - Role of microRNAs in lung cancer: microRNA signatures in cancer prognosis.
AB  - Lung cancer-related mortality is the most common cause of cancer death worldwide.
      Detecting lung cancer at an earlier stage and, ideally, predicting who will
      develop the disease and particularly the most aggressive forms of cancer are the
      biggest challenge. MicroRNAs (miRNAs) are short, noncoding RNA molecules with
      regulatory function on protein-coding genes. Because of their fundamental role in
      development and differentiation, their involvement in the biological mechanisms
      underlying tumorigenesis, as well as their low complexity, stability, and easy
      detection, they represent a promising class of tissue- and blood-based biomarkers
      of cancer. We summarize the current literature on the use of microRNAs as
      diagnostic and prognostic tools in lung cancer and discuss the relevant clinical
      implications of these findings.

PMID- 22647363
TI  - The microRNA-17-92 family of microRNA clusters in development and disease.
AB  - Overwhelming experimental evidence accumulated over the past decade indicates
      that microRNAs (miRNAs) are key regulators of gene expression in animals and
      plants and play important roles in development, homeostasis, and disease. The miR
      17-92 family of miRNA clusters is composed of 3 related, highly conserved,
      polycistronic miRNA genes that collectively encode for a total of 15 miRNAs. We
      discuss recent studies demonstrating that these miRNAs are essential for
      vertebrate development and homeostasis. We also show how their mutation or
      deregulation contributes to the pathogenesis of a variety of human diseases,
      including cancer and congenital developmental defects. Finally, we discuss the
      current evidence suggesting how the different miRNAs encoded by these 3 clusters
      can functionally cooperate to fine-tune signaling and developmental pathways.

PMID- 22647365
TI  - The therapeutic potential of microRNAs in cancer.
AB  - MicroRNAs (miRNAs) have been uncovered as important posttranscriptional
      regulators of nearly every biological process in the cell. Furthermore, mounting
      evidence implies that miRNAs play key roles in the pathogenesis of cancer and
      that many miRNAs can function either as oncogenes or tumor suppressors. Thus,
      miRNAs have rapidly emerged as promising targets for the development of novel
      anticancer therapeutics. The development of miRNA-based cancer therapeutics
      relies on restoring the activity of tumor suppressor miRNAs using double-stranded
      miRNA mimics or inhibition of oncogenic miRNAs using single-stranded antisense
      oligonucleotides, termed antimiRs. In the present review, we focus on recent
      advancements in the discovery and development of miRNA-based cancer therapeutics
      using these 2 approaches. In addition, we summarize selected studies, in which
      modulation of miRNA activity in preclinical cancer models in vivo has
      demonstrated promising therapeutic potential.

PMID- 22647366
TI  - The 22nd ion channel meeting, september 2011, france.
AB  - The 22(nd) Ion Channel Meeting was organized by the French Ion Channel Society
      (Association Canaux Ioniques) from the 25(th) to the 28(th) of September 2011 on
      the French Riviera (Giens). This year again, more than one hundred researchers
      from France, Europe and extra-European countries gathered to present and discuss
      their recent advances and future challenges in the ion channels and transporters
      field. The scientific committee organized a plenary lecture and five thematic
      symposia by inviting international researchers to present their recent
      outstanding work on themes as diverse as muscular channelopathies, regulation of
      channels by extracellular matrix, receptor-channels interactions, localization
      and distribution of ion channels, their involvement in the cell life and death,
      and finally how they participate in the evolution and adaptability of cellular
      excitability. These presentations are summarized in this meeting report. Two
      sessions of oral communications selected from submitted abstracts and two poster
      sessions were also organized to present the ongoing work of young researchers
      worldwide.

PMID- 22647367
TI  - Growth promotion and colonization of switchgrass (Panicum virgatum) cv. Alamo by
      bacterial endophyte Burkholderia phytofirmans strain PsJN.
AB  - BACKGROUND: Switchgrass is one of the most promising bioenergy crop candidates
      for the US. It gives relatively high biomass yield and can grow on marginal
      lands. However, its yields vary from year to year and from location to location.
      Thus it is imperative to develop a low input and sustainable switchgrass
      feedstock production system. One of the most feasible ways to increase biomass
      yields is to harness benefits of microbial endophytes. RESULTS: We demonstrate
      that one of the most studied plant growth promoting bacterial endophytes,
      Burkholderia phytofirmans strain PsJN, is able to colonize and significantly
      promote growth of switchgrass cv. Alamo under in vitro, growth chamber, and
      greenhouse conditions. In several in vitro experiments, the average fresh weight
      of PsJN-inoculated plants was approximately 50% higher than non-inoculated
      plants. When one-month-old seedlings were grown in a growth chamber for 30 days,
      the PsJN-inoculated Alamo plants had significantly higher shoot and root biomass
      compared to controls. Biomass yield (dry weight) averaged from five experiments
      was 54.1% higher in the inoculated treatment compared to non-inoculated control.
      Similar results were obtained in greenhouse experiments with transplants grown in
      4-gallon pots for two months. The inoculated plants exhibited more early tillers
      and persistent growth vigor with 48.6% higher biomass than controls. We also
      found that PsJN could significantly promote growth of switchgrass cv. Alamo under
      sub-optimal conditions. However, PsJN-mediated growth promotion in switchgrass is
      genotype specific. CONCLUSIONS: Our results show B. phytofirmans strain PsJN
      significantly promotes growth of switchgrass cv. Alamo under different
      conditions, especially in the early growth stages leading to enhanced production
      of tillers. This phenomenon may benefit switchgrass establishment in the first
      year. Moreover, PsJN significantly stimulated growth of switchgrass cv. Alamo
      under sub-optimal conditions, indicating that the use of the beneficial bacterial
      endophytes may boost switchgrass growth on marginal lands and significantly
      contribute to the development of a low input and sustainable feedstock production
      system.

PMID- 22647370
TI  - A single mutation in capsid protein VP1 (Q145E) of a genogroup C4 strain of human
      enterovirus 71 generates a mouse-virulent phenotype.
AB  - We modified the capsid protein of a human enterovirus 71 (HEV71) belonging to
      subgenogroup C4 (HEV71-C4) to generate a mouse virulent strain, based on the
      genetic information derived from our previous subgenogroup B3 mouse-adapted
      virus. Infectious clone-derived mutant virus populations containing the capsid
      protein mutations VP1-Q145E and VP1-Q145G were generated by site-directed
      mutagenesis of an infectious clone of a subgenogroup C4 strain. Viruses
      expressing the VP1-Q145E were virulent in 5-day-old BALB/c mice with 100 %
      mortality rate observed. Skeletal muscle appears to be the primary site of
      replication of this virus with limb muscle showing severe myositis. Virus was
      also isolated from spleen, liver, heart and brain of infected mice. This study
      demonstrates that introducing a key mutation into the HEV71 VP1 capsid protein is
      able to generate a mouse virulent HEV71 strain from a different genogroup as well
      as providing an alternative strategy for the generation of mouse virulent HEV71.

PMID- 22647371
TI  - The cysteine-rich proteins of beet necrotic yellow vein virus and tobacco rattle
      virus contribute to efficient suppression of silencing in roots.
AB  - Many plant viruses encode proteins that suppress RNA silencing, but little is
      known about the activity of silencing suppressors in roots. This study examined
      differences in the silencing suppression activity of different viruses in leaves
      and roots of Nicotiana benthamiana plants. Infection by tobacco mosaic virus,
      potato virus Y and cucumber mosaic virus but not potato virus X (PVX) resulted in
      strong silencing suppression activity of a transgene in both leaves and roots,
      whereas infection by beet necrotic yellow vein virus (BNYVV) and tobacco rattle
      virus (TRV) showed transgene silencing suppression in roots but not in leaves.
      For most viruses tested, viral negative-strand RNA accumulated at a very low
      level in roots, compared with considerable levels of positive-strand genomic RNA.
      Co-inoculation of leaves with PVX and either BNYVV or TRV produced an increase in
      PVX negative-strand RNA and subgenomic RNA (sgRNA) accumulation in roots. The
      cysteine-rich proteins (CRPs) BNYVV p14 and TRV 16K showed weak silencing
      suppression activity in leaves. However, when either of these CRPs was expressed
      from a PVX vector, there was an enhancement of PVX negative-strand RNA and sgRNA
      accumulation in roots compared with PVX alone. Such enhancement of PVX sgRNAs was
      also observed by expression of CRPs of other viruses and the well-known
      suppressors HC-Pro and p19 but not of the potato mop-top virus p8 CRP. These
      results indicate that BNYVV- and TRV-encoded CRPs suppress RNA silencing more
      efficiently in roots than in leaves.

PMID- 22647372
TI  - A doxycycline-dependent human immunodeficiency virus type 1 replicates in vivo
      without inducing CD4+ T-cell depletion.
AB  - A novel genetic approach for the control of virus replication was used for the
      design of a conditionally replicating human immunodeficiency virus (HIV) variant,
      HIV-rtTA. HIV-rtTA gene expression and virus replication are strictly dependent
      on the presence of a non-toxic effector molecule, doxycycline (dox), and thus can
      be turned on and off at will in a graded and reversible manner. The in vivo
      replication capacity, pathogenicity and genetic stability of this HIV-rtTA
      variant were evaluated in a humanized mouse model of haematopoiesis that harbours
      lymphoid and myeloid components of the human immune system (HIS). Infection of
      dox-fed BALB Rag/gammac HIS (BRG-HIS) mice with HIV-rtTA led to the establishment
      of a productive infection without CD4(+) T-cell depletion. The virus did not show
      any sign of escape from dox control for up to 10 weeks after the onset of
      infection. No reversion towards a functional Tat-transactivating responsive (TAR)
      RNA element axis was observed, confirming the genetic stability of the HIV-rtTA
      variant in vivo. These results demonstrate the proof of concept that HIV-rtTA
      replicates efficiently in vivo. HIV-rtTA is a promising tool for fundamental
      research to study virus-host interactions in vivo in a controlled fashion.

PMID- 22647374
TI  - Complete coding sequence and molecular epidemiological analysis of Sindbis virus
      isolates from mosquitoes and humans, Finland.
AB  - Sindbis virus (SINV) is an arthropod-borne alphavirus, which causes rash
      arthritis, particularly in Finland. SINV is transmitted by mosquitoes in Finland
      but thus far no virus has been isolated from mosquitoes. In this study, we report
      the isolation of the first SINV strain from mosquitoes in Finland and its full
      length protein-coding sequence. We furthermore describe the full-length coding
      sequence of six SINV strains previously isolated from humans in Finland and from
      a mosquito in Russia. The strain isolated from mosquitoes (Ilomantsi-2005M) was
      very closely related to all the other Northern European SINV strains. We found 9
      aa positions, of which five in the nsP3 protein C terminus, to be distinctive
      signatures for the Northern European strains that may be associated with vector
      or host species adaptation. Phylogenetic analyses further indicate that SINV has
      a local circulation in endemic regions in Northern Europe and no novel strains
      are frequently being introduced.

PMID- 22647373
TI  - Application of next-generation sequencing technologies in virology.
AB  - The progress of science is punctuated by the advent of revolutionary technologies
      that provide new ways and scales to formulate scientific questions and advance
      knowledge. Following on from electron microscopy, cell culture and PCR, next
      generation sequencing is one of these methodologies that is now changing the way
      that we understand viruses, particularly in the areas of genome sequencing,
      evolution, ecology, discovery and transcriptomics. Possibilities for these
      methodologies are only limited by our scientific imagination and, to some extent,
      by their cost, which has restricted their use to relatively small numbers of
      samples. Challenges remain, including the storage and analysis of the large
      amounts of data generated. As the chemistries employed mature, costs will
      decrease. In addition, improved methods for analysis will become available,
      opening yet further applications in virology including routine diagnostic work on
      individuals, and new understanding of the interaction between viral and host
      transcriptomes. An exciting era of viral exploration has begun, and will set us
      new challenges to understand the role of newly discovered viral diversity in both
      disease and health.

PMID- 22647375
TI  - Natural interspecies recombinant bovine/porcine enterovirus in sheep.
AB  - Members of the genus Enterovirus (family Picornaviridae) are believed to be
      common and widespread among humans and different animal species, although only a
      few enteroviruses have been identified from animal sources. Intraspecies
      recombination among human enteroviruses is a well-known phenomenon, but only a
      few interspecies examples have been reported and, to our current knowledge, none
      of these have involved non-primate enteroviruses. In this study, we report the
      detection and complete genome characterization (using RT-PCR and long-range PCR)
      of a natural interspecies recombinant bovine/porcine enterovirus (ovine
      enterovirus type 1; OEV-1) in seven (44 %) of 16 faecal samples from 3-week-old
      domestic sheep (Ovis aries) collected in two consecutive years. Phylogenetic
      analysis of the complete coding region revealed that OEV-1 (ovine/TB4
      OEV/2009/HUN; GenBank accession no. JQ277724) was a novel member of the species
      Porcine enterovirus B (PEV-B), implying the endemic presence of PEV-B viruses
      among sheep. However, the 5' UTR of OEV-1 showed a high degree of sequence and
      structural identity to bovine enteroviruses. The presumed recombination
      breakpoint was mapped to the end of the 5' UTR at nucleotide position 814 using
      sequence and SimPlot analyses. The interspecies-recombinant nature of OEV-1
      suggests a closer relationship among bovine and porcine enteroviruses, enabling
      the exchange of at least some modular genetic elements that may evolve
      independently.

PMID- 22647376
TI  - Not all autophagy is equal.
AB  - Autophagy is an important mechanism in cancer cell survival and tumor growth and
      plays both pro- and anti-oncogenic roles. However, the biochemical basis for
      these diverse functions is not well understood. Our work provides new evidence
      for the existence of two separate autophagic programs regulated in an opposite
      manner by the von Hippel-Lindau tumor suppressor (VHL). These programs, marked by
      differential requirements for LC3B vs. LC3C, play tumor-promoting and tumor
      suppressing roles in renal cancer.

PMID- 22647377
TI  - A comparison of three methods for integrating historical information for Bayesian
      model averaged benchmark dose estimation.
AB  - The benchmark dose (BMD) approach has been accepted as a valuable tool for risk
      assessment but still faces significant challenges associated with combining
      environmental hazard information from multiple sources and selecting an
      appropriate BMD/BMDL estimate from the results of a set of acceptable dose
      response models. The main objective of this study is to compare and examine how
      historical information, especially incompatible data, can impact the Bayesian
      model averaged BMD estimate through different integration methods. Based on the
      Bayesian model averaging (BMA) for the benchmark dose estimation, three methods
      of integration are investigated: (1) pooled data analysis, which combines all
      dose groups into one dataset; (2) the Bayesian hierarchical model, which takes
      both between-study and within-study uncertainty into account by building multiple
      levels of distributions to quantitatively describe parameters in dose-response
      models; and (3) the power prior method, which allows researchers to weigh the
      prior information incorporated through a power parameter. Combined historical
      information can have different levels of impact on the current model weight and
      BMD estimates depending on the method of integration. The pooled data analysis,
      which has the largest impact on the current BMA BMD estimate, has limited
      applicability and might be statistically and biologically flawed. The Bayesian
      hierarchical model, with a reasonable structure to combine information, can
      slightly change the current estimates of the model weights and BMD. The power
      prior method has little influence on current estimates when data are highly
      incompatible even if the prior information is fully considered.

PMID- 22647378
TI  - The tumor suppressor HINT1 regulates MITF and beta-catenin transcriptional
      activity in melanoma cells.
AB  - Histidine triad nucleotide-binding protein 1 (HINT1) is a haploinsufficient tumor
      suppressor gene that inhibits the Wnt/beta-catenin pathway in colon cancer cells
      and Microphthalmia-associated transcription factor (MITF) activity in human mast
      cells. MITF and beta-catenin play a central role in melanocyte and melanoma cell
      survival, and this study aimed to investigate the effects of HINT1 on the MITF
      and beta-catenin pathways in malignant melanoma cells. We found that HINT1
      inhibits MITF and beta-catenin transcriptional activity, and both proteins can be
      co-immunoprecipitated with an anti-HINT1-specific antibody in melanoma cell
      lines. Stable, constitutive overexpression of the HINT1 protein in human melanoma
      cells significantly impaired cell proliferation in vitro and tumorigenesis in
      vivo. These effects were associated with a decreased expression of cyclin D1 and
      BCL2, well known MITF and beta-catenin transcription targets, respectively. We
      also demonstrated that BCL2 and cyclin D1 can partially rescue the HINT1-driven
      phenotype. Moreover, we found in ChIP assays that HINT1 binds the chromatin at
      MITF and beta-catenin sites in BCL2 and cyclin D1 promoters, respectively, and
      that mSIN3a and HDAC1, well known transcriptional repressors, can be co
      immunoprecipitated with an anti-HINT1-specific antibody. These findings support
      the tumor suppressor activity of HINT1 gene in melanoma cells by promoting the
      formation of non-functional complexes with oncogenic transcription factors like
      MITF and beta-catenin.

PMID- 22647379
TI  - VEGF-A engages at least three tyrosine kinases to activate PI3K/Akt.

PMID- 22647380
TI  - Sarcopenia is more prevalent in men than in women after hip fracture: a cross
      sectional study of 591 inpatients.
AB  - Our aim was to compare the prevalence of sarcopenia in men and women with hip
      fracture. We studied 591 of 630 hip fracture inpatients consecutively admitted to
      our Rehabilitation ward. All the patients underwent a Dual-Energy X-Ray
      Absorptiometry (DXA) scan 18.4 +/- 8.7 (mean +/- SD) days after hip fracture
      occurrence. Sarcopenia was defined when appendicular lean mass divided by height
      squared was less than two standard deviations below the mean of the young
      reference group obtained from population based studies. Using normative data from
      the New Mexico Elder Health Study, 340 of the 531 women (64.0%), and 57 of the 60
      men (95.0%) had sarcopenia. Using normative data from the survey performed in
      Rochester, Minnesota, 116 of the 531 women (21.8%), and 52 of the 60 men (86.7%)
      had sarcopenia. After adjustment for age, time between fracture occurrence and
      DXA scan, number of medications in use, and number of concomitant diseases, men
      had a significantly higher prevalence of sarcopenia than women (p < 0.001). The
      adjusted odds ratio was either 10.54 (95% CI from 3.25 to 34.16) or 23.64 (from
      10.8 to 51.6) depending on the reference population adopted. Our data shows a
      high proportion of sarcopenic subjects after hip-fracture. Sarcopenia was
      significantly more prevalent in men than in women. Relevancy of prevention and
      treatment of muscle loss is emphasized, particularly in men.

PMID- 22647381
TI  - The prevalence of stroke and the association between stroke and depression among
      a very old population.
AB  - There are few studies comparing those who have had and have not had a stroke
      among those aged 80 years and over, the very old. The aim of this paper was to
      investigate the prevalence of stroke and the association between stroke and
      depression in a very old population. This paper is based on cross-sectional data
      from a population-based study performed between 2005 and 2007. Half of those aged
      85 years, all 90-, and 95-year-olds and older in eight urban and rural
      municipalities in northern Sweden and Finland were invited to participate. A
      sample of 601 individuals who participated fully in the study was selected. Data
      were collected through assessments, structured interviews and investigation of
      medical charts. A specialist in geriatric medicine determined disease status for
      depression based on medical records and results from the Geriatric Depression
      Scale (GDS)-15, the Montgomery Asberg Depression Rating Scale (MADRS) and the
      Organic Brain Syndrome (OBS) scale, and for stroke based on medical records and
      reported disease. The prevalence of stroke was 21.5%. The prevalence of
      depression was 50.4% among those with stroke compared to 34.3% among those
      without stroke (OR 1.944, p<0.001). In a logistic regression model adjusted for
      several demographic variables, diseases and functional level, stroke was
      independently associated with depression (OR 1.644, p=0.038). A large proportion
      of those with depression, both with and without stroke, were not receiving
      antidepressant medication. In conclusion, the stroke prevalence was high and
      stroke showed a strong association with depression among very old people.

PMID- 22647382
TI  - Social health and nutrition impacts of community kitchens: a systematic review.
AB  - OBJECTIVE: Community kitchens have been implemented by communities as a public
      health strategy to prevent food insecurity through reducing social isolation,
      improving food and cooking skills and empowering participants. The aim of the
      present paper was to investigate whether community kitchens can improve the
      social and nutritional health of participants and their families. DESIGN: A
      systematic review of the literature was conducted including searches of seven
      databases with no date limitations. SETTING: Community kitchens internationally.
      SUBJECTS: Participants of community kitchens across the world. RESULTS: Ten
      studies (eight qualitative studies, one mixed-method study and one cross
      sectional study) were selected for inclusion. Evidence synthesis suggested that
      community kitchens may be an effective strategy to improve participants' cooking
      skills, social interactions and nutritional intake. Community kitchens may also
      play a role in improving participants' budgeting skills and address some concerns
      around food insecurity. Long-term solutions are required to address income
      related food insecurity. CONCLUSIONS: Community kitchens may improve social
      interactions and nutritional intake of participants and their families. More
      rigorous research methods, for both qualitative and quantitative studies, are
      required to effectively assess the impact of community kitchens on social and
      nutritional health in order to confidently recommend them as a strategy in
      evidence-based public health practice.

PMID- 22647383
TI  - Efficient driver drowsiness detection at moderate levels of drowsiness.
AB  - Previous research on driver drowsiness detection has focused primarily on lane
      deviation metrics and high levels of fatigue. The present research sought to
      develop a method for detecting driver drowsiness at more moderate levels of
      fatigue, well before accident risk is imminent. Eighty-seven different driver
      drowsiness detection metrics proposed in the literature were evaluated in two
      simulated shift work studies with high-fidelity simulator driving in a controlled
      laboratory environment. Twenty-nine participants were subjected to a night shift
      condition, which resulted in moderate levels of fatigue; 12 participants were in
      a day shift condition, which served as control. Ten simulated work days in the
      study design each included four 30-min driving sessions, during which
      participants drove a standardized scenario of rural highways. Ten straight and
      uneventful road segments in each driving session were designated to extract the
      87 different driving metrics being evaluated. The dimensionality of the overall
      data set across all participants, all driving sessions and all road segments was
      reduced with principal component analysis, which revealed that there were two
      dominant dimensions: measures of steering wheel variability and measures of
      lateral lane position variability. The latter correlated most with an independent
      measure of fatigue, namely performance on a psychomotor vigilance test
      administered prior to each drive. We replicated our findings across eight curved
      road segments used for validation in each driving session. Furthermore, we showed
      that lateral lane position variability could be derived from measured changes in
      steering wheel angle through a transfer function, reflecting how steering wheel
      movements change vehicle heading in accordance with the forces acting on the
      vehicle and the road. This is important given that traditional video-based lane
      tracking technology is prone to data loss when lane markers are missing, when
      weather conditions are bad, or in darkness. Our research findings indicated that
      steering wheel variability provides a basis for developing a cost-effective and
      easy-to-install alternative technology for in-vehicle driver drowsiness detection
      at moderate levels of fatigue.

PMID- 22647385
TI  - Distribution of Nd3+ ions in oxyfluoride glass ceramics.
AB  - It has been an open question whether Nd3+ ions are incorporated into the
      crystalline phase in oxyfluoride glass ceramics or not. Moreover, relative
      research has indicated that spectra characters display minor differences between
      before and after heat treatment in oxyfluoride glass compared to similar Er3+-,
      Yb3+-, Tm3+-, Eu3+-, etc.-doped materials. Here, we have studied the distribution
      of Nd3+ ions in oxyfluoride glass ceramics by X-ray diffraction quantitative
      analysis and found that almost none of the Nd3+ ions can be incorporated into the
      crystalline phase. In order to confirm the rationality of the process, the
      conventional mathematical calculation and energy-dispersive spectrometry line
      scanning are employed, which show good consistency. The distribution of Nd3+ ions
      in oxyfluoride glass ceramics reported here is significant for further optical
      investigations and applications of rare-earth doped oxyfluoride glass ceramics.

PMID- 22647384
TI  - Whether, when and how chronic inflammation increases the risk of developing late
      onset Alzheimer's disease.
AB  - Neuropathological studies have revealed the presence of a broad variety of
      inflammation-related proteins (complement factors, acute-phase proteins, pro
      inflammatory cytokines) in Alzheimer's disease (AD) brains. These constituents of
      innate immunity are involved in several crucial pathogenic events of the
      underlying pathological cascade in AD, and recent studies have shown that innate
      immunity is involved in the etiology of late-onset AD. Genome-wide association
      studies have demonstrated gene loci that are linked to the complement system.
      Neuropathological and experimental studies indicate that fibrillar amyloid-beta
      (Abeta) can activate the innate immunity-related CD14 and Toll-like receptor
      signaling pathways of glial cells for pro-inflammatory cytokine production. The
      production capacity of this pathway is under genetic control and offspring with a
      parental history of late-onset AD have a higher production capacity for pro
      inflammatory cytokines. The activation of microglia by fibrillar Abeta deposits
      in the early preclinical stages of AD can make the brain susceptible later on for
      a second immune challenge leading to enhanced production of pro-inflammatory
      cytokines. An example of a second immune challenge could be systemic inflammation
      in patients with preclinical AD. Prospective epidemiological studies show that
      elevated serum levels of acute phase reactants can be considered as a risk factor
      for AD. Clinical studies suggest that peripheral inflammation increases the risk
      of dementia, especially in patients with preexistent cognitive impairment, and
      accelerates further deterioration in demented patients. The view that peripheral
      inflammation can increase the risk of dementia in older people provides scope for
      prevention.

PMID- 22647386
TI  - Morphology and phylogeny of Reticulitermes sp. (Isoptera, Rhinotermitidae) from
      Cyprus.
AB  - Taxonomy and phylogeny of termites of the genus Reticulitermes in central and
      eastern Mediterranean lands are poorly understood, partly due to insufficient
      sampling. This study aims to contribute to the knowledge of east Mediterranean
      termites by presenting morphological and molecular data on Reticulitermes from
      Cyprus. Samples from 15 colonies were collected throughout the island.
      Qualitative and quantitative morphological characters were analyzed for alate and
      soldier castes. Partial sequences of the mitochondrial genes COII and 16S were
      used to evaluate genetic diversity of Cypriot colonies and to determine their
      phylogenetic relationships with taxa from central and eastern Mediterranean
      areas. Cypriot alates have some morphological features in common with the Israeli
      R. clypeatus: an enlarged postclypeus and a wide unpigmented margin of the eye.
      They are larger than R. clypeatus but smaller than western European species, such
      as R. banyulensis, R. lucifugus corsicus and R. grassei. For Cypriot soldiers,
      two size groups were identified, possibly in relation with the age of their
      mother colonies. Phylogenetic analysis shows that, contrary to what might be
      expected, the samples with the highest affinity with Cypriot samples are not
      those from the nearby mainland (south Turkey, Israel), but from north-eastern
      Greece. Comprehensive sampling in the nearby mainland is lacking, so the
      possibility that populations exist it that region with an affinity towards
      Cypriot Reticulitermes sp. cannot be ruled out. Together with samples from the
      Halkidiki peninsula, north-eastern Greece, northern Turkey and Crete, Cypriot
      Reticulitermes form a well-supported north-eastern Mediterranean clade.

PMID- 22647388
TI  - Air pollution and hospitalization for acute complications of diabetes in Chile.
AB  - Exposure to air pollution has been shown to cause insulin resistance in mice. To
      determine the relevance to humans, we tested the association between daily air
      pollution concentrations and daily hospitalization for acute serious
      complications of diabetes, coma and ketoacidosis, in Santiago between 2001 and
      2008, using generalized linear models with natural splines to control for long
      term trends. For an interquartile range (IQR) increase in air pollutant, the
      relative risks (95% CI) of hospitalization for diabetes were: 1.15 (1.10, 1.20)
      for carbon monoxide (IQR=1.00); 1.07 (0.98, 1.16) for ozone (IQR=63.50); 1.14
      (1.06, 1.22) for sulfur dioxide (IQR=5.88); 1.12(1.05, 1.20) for nitrogen dioxide
      (IQR=27.94); 1.11 (1.07, 1.15) for particulate matter<=10 MUm
      diameter(IQR=34.00); and 1.11 (1.06, 1.16) for fine particulate matter <=2.5 MUm
      diameter (IQR=18.50). Results were similar when stratified by age, sex and
      season. Air pollution appears to increase the risk of acute complications of
      diabetes requiring hospitalization, suggesting that improvements in air quality
      may reduce morbidity from diabetes.

PMID- 22647387
TI  - Design and current status of CONTINT: continuous versus interrupted abdominal
      wall closure after emergency midline laparotomy - a randomized controlled
      multicenter trial [NCT00544583].
AB  - BACKGROUND: The optimal strategy for abdominal wall closure has been an issue of
      ongoing debate. Available studies do not specifically enroll patients who undergo
      emergency laparotomy and thus do not consider the distinct biological
      characteristics of these patients. The present randomized controlled trial
      evaluates the efficacy and safety of two commonly applied abdominal wall closure
      strategies in patients undergoing primary emergency midline laparotomy.
      METHODS/DESIGN: The CONTINT trial is a multicenter, open label, randomized
      controlled trial with a two-group parallel design. Patients undergoing a primary
      emergency midline laparotomy are enrolled in the trial. The two most commonly
      applied strategies of abdominal wall closure after midline laparotomy are
      compared: the continuous, all-layer suture technique using slowly absorbable
      monofilament material (two Monoplus loops) and the interrupted suture technique
      using rapidly absorbable braided material (Vicryl sutures). The primary endpoint
      within the CONTINT trial is an incisional hernia within 12 months or a burst
      abdomen within 30 days after surgery. As reliable data on this primary endpoint
      is not available for patients undergoing emergency surgery, an adaptive interim
      analysis will be conducted after the inclusion of 80 patients, allowing early
      termination of the trial if necessary or modification of design characteristics
      such as recalculation of sample size. DISCUSSION: This is a randomized controlled
      multicenter trial with a two-group parallel design to assess the efficacy and
      safety of two commonly applied abdominal wall closure strategies in patients
      undergoing primary emergency midline laparotomy. TRIAL REGISTRATION: NCT00544583.

PMID- 22647389
TI  - A high throughput capillary electrophoresis method to obtain pharmacokinetics and
      quality attributes of a therapeutic molecule in circulation.
AB  - Therapeutic proteins circulating in blood are in a highly crowded, redox
      environment at high temperatures of ~37 degrees C. These molecules circulate in
      the presence of enzymes and other serum proteins making it difficult to predict
      from in vitro studies the stability, aggregation or pharmacokinetics of a
      therapeutic protein in vivo. Here, we describe use of a high throughput capillary
      electrophoresis based microfluidic device (LabChip GXII) to obtain
      pharmacokinetics (PK) of a fluorescently labeled human mAb directly from serum.
      The non-labeled and labeled mAbs were evaluated in single dose rat PK studies
      using a traditional ELISA method or LabChip GXII, respectively. The fluorescent
      dye did not significantly alter clearance of this particular mAb, and PK
      parameters were comparable for labeled and unlabeled molecules. Further, from the
      CE profile we concluded that the mAb was resistant to fragmentation or
      aggregation during circulation. In a follow-up experiment, dimers were generated
      from the mAb using photo-induced cross-linking of unmodified proteins (PICUP) and
      labeled with the same fluorophore. The extent of dimerization was incomplete and
      some monomer and higher molecular weight species were found in the preparation.
      In rat PK studies, the serum concentration-time profile of the three entities
      present in the dimer preparation could be followed simultaneously with the GXII
      technology. While further studies are warranted, we believe this method could be
      adapted to obtain PK of different forms of antibodies (oxidized, deamidated or
      various glycosylated species) and other proteins.

PMID- 22647390
TI  - Meeting the health and social care needs of pregnant asylum seekers; midwifery
      students' perspectives: part 3; "the pregnant woman within the global context";
      an inclusive model for midwifery education to address the needs of asylum seeking
      women in the UK.
AB  - AIM: to describe the conceptualisation and development of an inclusive
      educational model. The model is designed to facilitate pre-registration midwifery
      students' learning around the health and social care needs of pregnant women
      seeking asylum in the United Kingdom. BACKGROUND: current literature has
      identified a concern about the standard of maternity care experienced by asylum
      seeking women accessing maternity services in the United Kingdom. In response to
      this, a doctorate study was undertaken which focused on examining the way in
      which a group of midwifery students approached the provision of care for asylum
      seekers. This study revealed difficulties that these students had both in
      identifying these women's needs and also in the wider care issues in practice.
      Consequently, one of the recommendations was to ameliorate these difficulties
      through midwifery education. METHODS: the key findings from this study were used
      together with relevant supporting literature to construct "the pregnant woman
      within the global context" model for midwifery education. RESULTS: The model is
      designed to facilitate a holistic assessment of need rather than focusing on the
      physical assessment at the expense of other aspects of care. It incorporates
      wider factors, on a global level, which could impact on the health and social
      care needs of a pregnant woman seeking asylum. It also prompts students to
      consider the influence of dominant discourses on perceptions of asylum seek;ing
      and is designed to encourage students' to question these discourses.
      RECOMMENDATIONS: this model can be used in midwifery education to prepare
      students in caring for pregnant women seeking asylum. It may be especially
      helpful when students have close contact with pregnant women seeking asylum, for
      example through caseloading. Further research is recommended to evaluate the
      effectiveness of this model in enhancing the care of asylum seeking women in the
      United Kingdom.

PMID- 22647391
TI  - Naturally occurring endo-siRNA silences LINE-1 retrotransposons in human cells
      through DNA methylation.
AB  - Long interspersed nuclear element 1 (LINE-1) retrotransposons are mutagens that
      are capable of generating deleterious mutations by inserting themselves into
      genes and affecting gene function in the human genome. In normal cells, the
      activity of LINE-1 retrotransposon is mostly repressed, maintaining a stable
      genome structure. In contrast, cancer cells are characterized by aberrant
      expression of LINE-1 retrotransposons, which, in principle, have the potential to
      contribute to genomic instability. The mechanistic pathways that regulate LINE-1
      expression remain unclear. Using deep-sequencing small RNA analysis, we
      identified a subset of differentially expressed endo-siRNAs that directly
      regulate LINE-1 expression. Detailed analyses suggest that these endo-siRNAs are
      significantly depleted in human breast cancer cells compared with normal breast
      cells. The overexpression of these endo-siRNAs in cancer cells markedly silences
      endogenous LINE-1 expression through increased DNA methylation of the LINE-1 5'
      UTR promoter. The finding that endo-siRNAs can silence LINE-1 activity through
      DNA methylation suggests that a functional link exists between the expression of
      endo-siRNAs and LINE-1 retrotransposons in human cells.

PMID- 22647392
TI  - Arsenic and associated trace-elements in groundwater from the Chaco-Pampean
      plain, Argentina: results from 100 years of research.
AB  - The Chaco-Pampean plain, Argentina, is a vast geographical unit (1,000,000 km2)
      affected by high arsenic (As) concentrations in universal oxidizing groundwater.
      The socio-economic development of the region is restricted by water availability
      and its low quality caused by high salinity and hardness. In addition, high As
      and associated trace-elements (F, U, V, B, Se, Sb, Mo) concentrations of geogenic
      origin turn waters unsuitable for human consumption. Shallow groundwater with
      high As and F concentrations (ranges: <10-5300 MUg As/L; 51-7,340 MUg F/L)
      exceeding the WHO guideline values (As: 10 MUg/L; F: 1,500 MUg/L) introduces a
      potential risk of hydroarsenicism disease in the entire region and fluorosis in
      some areas. The rural population is affected (2-8 million inhabitants).
      Calcareous loess-type sediments and/or intercalated volcanic ash layers in
      pedosedimentary sequences hosting the aquifers are the sources of contaminant
      trace-elements. Large intra and interbasin variabilities of trace-element
      concentrations, especially between shallow and deep aquifers have been observed.
      All areas of the Chaco-Pampean plain were affected in different grades: the Chaco
      Saltena plain (in the NNE of the region) and the northern La Pampa plain (in the
      center-south) have been shown the highest concentrations. The ranges of As and F
      contents in loess-sediments are 6-25 and 534-3340 mg/kg, respectively in the Sali
      River basin. Three key processes render high As concentrations in shallow
      aquifers: i) volcanic glass dissolution and/or hydrolysis and leaching of
      silicates minerals hosted in loess; ii) desorption processes from the surface of
      Al-, Fe- and Mn-oxi-hydroxides (coating lithic fragments) at high pH and
      mobilization as complex oxyanions (As and trace elements)in Na-bicarbonate type
      groundwaters; and iii) evaporative concentration in areas with semiarid and arid
      climates. Local factors play also an important role in the control of high As
      concentrations, highly influenced by lithology-mineralogy, soils-geomorphology,
      actual climate and paleoclimates, hydraulic parameters, and residence time of
      groundwaters.

PMID- 22647393
TI  - Oxidative degradation of alternative gasoline oxygenates in aqueous solution by
      ultrasonic irradiation: mechanistic study.
AB  - Widespread pollution has been associated with gasoline oxygenates of branched
      ethers methyl tert-butyl ether (MTBE), di-isopropyl ether (DIPE), ethyl tert
      butyl ether (ETBE), and tert-amyl ether (TAME) which enter groundwater. The
      contaminated plume develops rapidly and treatment for the removal/destruction of
      these ethers is difficult when using conventional methods. Degradation of MTBE,
      with biological methods and advanced oxidation processes, are rather well known;
      however, fewer studies have been reported for degradation of alternative
      oxygenates. Degradation of alternative gasoline oxygenates (DIPE, ETBE, and TAME)
      by ultrasonic irradiation in aqueous oxygen saturation was investigated to
      elucidate degradation pathways. Detailed degradation mechanisms are proposed for
      each gasoline oxygenate. The common major degradation pathways are proposed to
      involve abstraction of alpha-hydrogen atoms by hydroxyl radicals generated during
      ultrasound cavitation and low temperature pyrolytic degradation of ETBE and TAME.
      Even some of the products from beta-H abstraction overlap with those from high
      temperature pyrolysis, the effect of beta-H abstraction was not shown clearly
      from product study because of possible 1,5 H-transfer inside cavitating bubbles.
      Formation of hydrogen peroxide and organic peroxides was also determined during
      sonolysis. These data provide a better understanding of the degradation pathways
      of gasoline oxygenates by sonolysis in aqueous solutions. The approach may also
      serve as a model for others interested in the details of sonolysis.

PMID- 22647394
TI  - Determination and stability assessment of clarithromycin in human plasma using RP
      LC with electrochemical detection.
AB  - A selective, sensitive and stability-indicating reversed-phase high-performance
      liquid chromatography method was developed and validated for the determination of
      clarithromycin antibiotic in human plasma. Liquid chromatography was performed on
      a 5-um (100 * 4.6 mm) C8 column at 40 degrees C. The mobile phase consisted of
      acetonitrile with 0.045M H(3)PO(4) (37:63, v/v) adjusted to pH 6.7 and pumped at
      a flow rate of 1.2 mL/min. Detections were monitored on an electrochemical
      detector operated at a potential of 0.85 V with glassy carbon electrode against
      Ag/AgCl reference electrode. Each analysis required 13 min and quantification
      over the range of 0.05-5.0 ug/mL of plasma was linear, as indicated by a
      correlation coefficient (R(2)), 0.9999. The method was validated according to
      international guidelines. Data with respect to accuracy, within-run and between
      run, were close to 100% with 4% precision. Absolute recovery was 95%. The limit
      of quantification was 0.05 ug/mL. Neither endogenous substances nor commonly used
      drugs were found to interfere with the retention times of analytes. Stock
      solutions and calibration standards of the drug and quality control preparations
      were demonstrated to be stable at room temperature and -20 degrees C for long and
      short periods of time. Eventually, the proposed method was successfully applied
      to quantify clarithromycin in spiked human plasma and real samples from healthy
      volunteers, indicating the utility and throughput of this method for clinical and
      bioavailability studies.

PMID- 22647395
TI  - Comment to "characteristics of autoimmune pancreatitis based on serum IgG4
      level".

PMID- 22647396
TI  - Defining the severity of liver dysfunction in patients with hepatocellular
      carcinoma by the model for end-stage liver disease-derived systems.
AB  - BACKGROUND: The model for end-stage liver disease (MELD) and serum sodium (Na)
      are important markers for liver functional reserve in patients with
      hepatocellular carcinoma. We aimed to determine the best model to define the
      severity of liver dysfunction in terms of outcome prediction among the 4
      currently used systems (MELD, MELDNa, MELD-Na and ReFit MELDNa). METHODS: A total
      of 2308 prospectively enrolled patients with hepatocellular carcinoma were
      analysed. The prognostic ability was compared by the Akaike information
      criterion. RESULTS: MELDNa had the best prognostic accuracy overall, and for
      patients receiving curative and non-curative treatments, followed by MELD-Na,
      MELD and ReFit MELDNa. When patients were categorized into <8, 8-12, 12-16, 16-20
      and >20, the adjusted risk ratios for MELDNa were 1.065 (p=0.46), 0.996
      (p=0.973), 1.38 (p=0.048) and 1.563 (p=0.003) for the scores of 8-12, 12-16, 16
      20 and >20, respectively, compared to the group with scores <8. The adjusted risk
      ratio for MELDNa was 1.014 (95% confidence interval, 1.001-1.027; p=0.034) per
      unit score increment in the Cox model. CONCLUSIONS: The MELDNa is the best marker
      to define the severity of liver dysfunction in hepatocellular carcinoma patients
      independent of treatment strategy. The ReFit MELDNa does not enhance the
      predictive accuracy of the MELD.

PMID- 22647397
TI  - A systematic comparison of quantitative high-resolution DNA methylation analysis
      and methylation-specific PCR.
AB  - Assessment of DNA methylation has become a critical factor for the
      identification, development and application of methylation based biomarkers. Here
      we describe a systematic comparison of a quantitative high-resolution mass
      spectrometry-based approach (MassARRAY), pyrosequencing and the broadly used
      methylation-specific PCR (MSP) technique analyzing clinically relevant
      epigenetically silenced genes in acute myeloid leukemia (AML). By MassARRAY and
      pyrosequencing, we identified significant DNA methylation differences at the ID4
      gene promoter and in the 5' region of members of the SFRP gene family in 62 AML
      patients compared with healthy controls. We found a good correlation between data
      obtained by MassARRAY and pyrosequencing (correlation coefficient R(2) = 0.88).
      MSP-based assessment of the identical samples showed less pronounced differences
      between AML patients and controls. By direct comparison of MSP-derived and
      MassARRAY-based methylation data as well as pyrosequencing, we could determine
      overestimation of DNA methylation data by MSP. We found sequence-context
      dependent highly variable cut-off values of quantitative DNA methylation values
      serving as discriminator for the two MSP methylation categories. Moreover, good
      agreements between quantitative methods and MSP could not be achieved for all
      investigated loci. Significant correlation of the quantitative assessment but not
      of MSP-derived methylation data with clinically important characteristics in our
      patient cohort demonstrated clinical relevance of quantitative DNA methylation
      assessment. Taken together, while MSP is still the most commonly applied
      technique for DNA methylation assessment, our data highlight advantages of
      quantitative approaches for precise characterization and reliable biomarker use
      of aberrant DNA methylation in primary patient samples, particularly.

PMID- 22647398
TI  - Isolated trigeminal nerve palsy with motor involvement as a presenting
      manifestation of multiple sclerosis in an equatorial region - a case report.
AB  - INTRODUCTION: Isolated cranial nerve palsies are considered to be an uncommon
      presenting feature of multiple sclerosis. Involvement of the trigeminal nerve,
      particularly its motor component as part of a clinically isolated syndrome of
      multiple sclerosis has rarely been reported in equatorial regions and no cases
      have been described in Sri Lanka thus far. CASE PRESENTATION: We report a case of
      isolated right sided trigeminal nerve palsy (Motor and Sensory) in a 34 year old
      previously well lady from urban Sri Lanka who was found to have characteristic
      lesions on Magnetic Resonance Imaging highly suggestive of multiple sclerosis.
      CONCLUSIONS: Multiple sclerosis should be considered in the differential
      diagnosis of patients who present with isolated cranial nerve palsies. Clinicians
      should have a high index of suspicion when evaluating such patients especially in
      low prevalence regions close to the equator. Early recognition and treatment of
      such a "Clinically Isolated Syndrome" may prevent early relapse.

PMID- 22647400
TI  - Interactions of aptamers with sera albumins.
AB  - The interactions of two short aptamers to human and bovine serum albumins were
      studied by fluorescence spectroscopic techniques. Intrinsic fluorescence of BSA
      and HSA were measured by selectively exciting their tryptophan residues. Gradual
      quenching was observed by titration of both proteins with aptamers. Aptamers are
      oligonucleic acid or peptide molecules that bind a specific target and can be
      used for both biotechnological and clinical purposes, since they present
      molecular recognition properties like that commonly found in antibodies. Two
      aptamers previously selected against the MUC1 tumour marker were used in this
      study, one selected for the protein core and one for the glycosylated MUC1. Stern
      Volmer graphs were plotted and quenching constants were estimated. Plots obtained
      from experiments carried out at 25  degrees C and 37  degrees C showed the
      quenching of fluorescence of by aptamers to be a collisional phenomenon. Stern
      Volmer constants estimated for HSA quenched by aptamer A were 1.68 * 10(5) (+/- 5
      * 10(3))M(-1) at 37  degrees C, and 1.37 * 10(5) (+/- 10(3))M(-1) at 25  degrees
      C; and quenched by aptamer B were 1.67 * 10(5) (+/- 5 * 10(3))M(-1) at 37 
      degrees C, and 1.32 * 10(5) (+/- 10(3))M(-1) at 25  degrees C. Results suggest
      that the primary binding site for aptamers on albumin is close to tryptophan
      residues in sub domain IIA.

PMID- 22647402
TI  - [Directorate of Health following a merger].

PMID- 22647401
TI  - A sensitive localized surface plasmon resonance sensor for determining
      mercury(II) ion using noble metal nanoparticles as probe.
AB  - The noble metal nanoparticles (NPs), including gold nanorods (AuNRs), gold
      nanospheres (AuNSs) and silver nanoplates (AgNPTs), were synthesized and Tween 20
      stabilized NPs (Tween 20-NPs) were used as the probes for determining Hg(2+).
      Hg(2+) was determined based on the strong affinity between Au (Ag) and Hg. Hg(2+)
      was reduced to Hg in the presence of sodium borohydride. Hg interacts with the
      NPs and the diameter of the NPs decreases with the increase of Hg(2+)
      concentration, which causes the shift in absorption peak of Tween 20-NPs. The
      peak shifts are linearly related to Hg(2+) concentrations. Compared with AuNSs
      and AgNPTs, when the AuNRs was used, the sensitivity for determining Hg(2+) was
      higher. The developed method shows a good selectivity for Hg(2+) and can be
      applied to the determination of Hg(2+) in water samples.

PMID- 22647403
TI  - [Should other health professionals than doctors be allowed to prescribe hormonal
      contraception?].

PMID- 22647406
TI  - [Successful resuscitation of a pulseless young woman with pulmonary embolus in
      rural Iceland].
AB  - A 27 year old woman suffered a witnessed cardiac arrest in rural Iceland and
      regained pulse after one hour's resuscitation. She was transported by an air
      ambulance to a tertiary medical center in Reykjavik where she was diagnosed with
      a large pulmonary embolus. After 24 hours therapeutic hypothermia she was
      rewarmed and extubated two days later. She was discharged from the hospital after
      two weeks neurologically intact. This case illustrates that even in rural
      circumstances the chain of survival works if all the links are strong, with early
      access, early resuscitation and early advanced care.

PMID- 22647405
TI  - [Body composition, aerobic fitness, physical activity and metabolic profile among
      18 year old Icelandic high-school students].
AB  - OBJECTIVE: The purpose of the study was to examine metabolic risk factors among
      18 year old high-school students and compare students attending vocational and
      traditional schools. MATERIAL AND METHODS: Participants (147 boys and 130 girls)
      were randomly selected. Physical activity (PA) was measured with pedometers and
      aerobic fitness (fitness) with maximal oxygen uptake test on a treadmill. Height,
      weight, waist circumference (WC), and body mass index (BMI) were measured and
      percentage body fat (%Fat) assessed with dual energy X-ray absorptiometry.
      Resting blood pressure (BP) and serum lipids and glucose were measured. RESULTS:
      According to BMI, 23% of the students were overweight/obese, 20% had elevated WC,
      and 51% increased %Fat. In addition, 11% of the students had high-density
      lipoprotein below recommended levels, and 8% had low-density lipoprotein and 9%
      triglycerides above advised values. Finally, 10% had borderline or high systolic
      BP. In contrast, 84% of the students had fair or higher levels of fitness,
      although only 34% reached recommended levels of daily PA. According to %Fat, a
      higher proportion of boys (33%) than girls (22%) were classified as obese
      (p=0.042) but a higher proportion of boys (57%) were very fit (57 vs. 24%,
      p<<0.001). Vocational students had lower levels of fitness (Cohen's d (Cd)=0.7)
      and PA (Cd=0.7), and higher %Fat (Cd=0.5), WC (Cd=0.6), and BP (Cd=0.3, p<0.05).
      CONCLUSION: Although fitness among 18 year old Icelandic high-school students
      seems generally good, their PA is low and %Fat elevated. Serum lipids and
      systolic BP are also increased in about 10% of the teenagers. Vocational students
      measure worse on most metabolic risk factors than traditional students.

PMID- 22647404
TI  - [Intensive care unit admissions following lobectomy or sublobar resections for
      non-small cell lung cancer].
AB  - INTRODUCTION: Following resection for non-small cell lung cancer (NSCLC),
      patients are usually admitted to the post-anesthesia care unit (PACU)for a few
      hours before admission to a general ward (GW). However, some patients need ICU
      admission, either immediately post-surgery or from the PACU or GW. The aim of
      this study was to investigate the indications and risk factors for ICU-admission.
      MATERIAL AND METHODS: A retrospective study of 252 patients who underwent
      lobectomy, wedge resection or segmentectomy for NSCLC in Iceland during 2001
      2010. Data was retrieved from medical records and patients admitted to the ICU
      compared to patients not admitted. RESULTS: Altogether 21 patients (8%) were
      admitted to the ICU, median length-of-stay being one day (range 1-68). In 11
      cases (52%) the reasons for admission were intraoperative problems, usually
      hypotension or excessive bleeding. Ten patients were admitted from the GW (n=4)
      or PACU (n=6), due to hypotension (n=4), heart and/or respiratory failure (n=4)
      and reoperation for bleeding (n=2). There were three ICU-readmissions. Patients
      admitted to the ICU were six years older (p=0.004) and more often had chronic
      obstructive pulmonary disease and/or coronary artery disease. Tumor size, pTNM
      stage, length of operation and the ratio of patients receiving TEA (thoracic
      epidural anaesthesia) were similar between groups. Over two-thirds of the ICU
      patients had minor complications and around half had major complications,
      compared to 30% and 4%, respectively, for controls. CONCLUSION: ICU-admissions
      are infrequent following non-pneumonectomy lung resections for NSCLC, these
      patients being older with cardiopulmonary comorbidities. In half of the cases,
      admission to the ICU directly follows surgery and ICU-readmissions are few.

PMID- 22647407
TI  - [Case of the month: patient with septic shock and massive intravascular
      haemolysis].

PMID- 22647408
TI  - Facile synthesis of hollow Cu2O octahedral and spherical nanocrystals and their
      morphology-dependent photocatalytic properties.
AB  - Herein, we report that octahedral and spherical Cu2O samples with hollow
      structures are synthesized in high yield by reducing Cu(EDA)22+ complex with
      hydrazine. A series of experiments are carried out to investigate the factors
      which impact on the morphology of the Cu2O samples. It is observed that
      ethylenediamine (EDA) serves as a molecular template in the formation of hollow
      structure. Octahedral Cu2O with solid structure is prepared without EDA. When EDA
      is added, Cu2O sample with hollow structure is formed. Different morphologies of
      Cu2O such as spherical and octahedral could be obtained by adjusting the
      concentration of EDA and NaOH. The temporal crystal growth mechanism is proposed.
      Furthermore, the photocatalytic activities of the as-prepared Cu2O nanoparticles
      are evaluated by monitoring two dyes (methyl orange and congo red) using UV
      visible spectrophotometer. Results show that the order of photocatalytic activity
      of Cu2O with different morphologies is as follows: hollow octahedral morphology >
      hollow sphere morphology > solid octahedral morphology. The hollow octahedral
      Cu2O nanoparticles would be a promising material on applications for
      photocatalytic degradation of organic pollutants.

PMID- 22647409
TI  - Fatty-acid oxidation and calcium homeostasis are involved in the rescue of
      bupivacaine-induced cardiotoxicity by lipid emulsion in rats.
AB  - OBJECTIVES: Lipid emulsion has been shown to be effective in resuscitating
      bupivacaine-induced cardiac arrest but its mechanism of action is not clear. Here
      we investigated whether fatty-acid oxidation is required for rescue of
      bupivacaine-induced cardiotoxicity by lipid emulsion in rats. We also compared
      the mitochondrial function and calcium threshold for triggering of mitochondrial
      permeability transition pore opening in bupivacaine-induced cardiac arrest before
      and after resuscitation with lipid emulsion. DESIGN: Prospective, randomized
      animal study. SETTING: University research laboratory. SUBJECTS: Adult male
      Sprague-Dawley rats. INTERVENTIONS: Asystole was achieved with a single dose of
      bupivacaine (10 mg/kg over 20 secs, intravenously) and 20% lipid emulsion
      infusion (5 mL/kg bolus, and 0.5 mL/kg/min maintenance), and cardiac massage
      started immediately. The rats in CVT-4325 (CVT) group were pretreated with a
      single dose of fatty-acid oxidation inhibitor CVT (0.5, 0.25, 0.125, or 0.0625
      mg/kg bolus intravenously) 5 mins prior to inducing asystole by bupivacaine
      overdose. Heart rate, ejection fraction, fractional shortening, the threshold for
      opening of mitochondrial permeability transition pore, oxygen consumption, and
      membrane potential were measured. The values are mean +/- SEM. MEASUREMENTS AND
      MAIN RESULTS: Administration of bupivacaine resulted in asystole. Lipid Emulsion
      infusion improved the cardiac function gradually as the ejection fraction was
      fully recovered within 5 mins (ejection fraction=64+/-4% and fractional
      shortening=36+/-3%, n=6) and heart rate increased to 239+/-9 beats/min (71%
      recovery, n=6) within 10 mins. Lipid emulsion was only able to rescue rats
      pretreated with low dose of CVT (0.0625 mg/kg; heart rate~181+/-11 beats/min at
      10 mins, recovery of 56%; ejection fraction=50+/-1%; fractional shortening=26+/
      0.6% at 5 mins, n=3), but was unable to resuscitate rats pretreated with higher
      doses of CVT (0.5, 0.25, or 0.125 mg/kg). The calcium-retention capacity in
      response to Ca2+ overload was significantly higher in cardiac mitochondria
      isolated from rats resuscitated with 20% lipid emulsion compared to the group
      that did not receive Lipid Emulsion after bupivacaine overdose (330+/-42 nmol/mg
      vs. 180+/-8.2 nmol/mg of mitochondrial protein, p<.05, n=3 in each group). The
      mitochondrial oxidative rate and membrane potential were similar in the
      bupivacaine group before and after resuscitation with lipid emulsion infusion.
      CONCLUSIONS: Fatty-acid oxidation is required for successful rescue of
      bupivacaine-induced cardiotoxicity by lipid emulsion. This rescue action is
      associated with inhibition of mitochondrial permeability transition pore opening.

PMID- 22647411
TI  - Catastrophic result of a huge right atrial mass.

PMID- 22647410
TI  - Intestinal ischemia/reperfusion enhances microglial activation and induces
      cerebral injury and memory dysfunction in rats.
AB  - OBJECTIVE: The mortality of critically ill patients associated with intestinal
      ischemia/reperfusion remains very high, which results from multiorgan dysfunction
      or failure due to intestinal injury induced by intestinal ischemia/reperfusion.
      This study was carried out to investigate whether intestinal ischemia/reperfusion
      can cause cerebral injury and concomitant memory dysfunction, and explore the
      potential mechanisms. DESIGN: Prospective, controlled, and randomized animal
      study. SETTING: University research laboratory. SUBJECTS: Male, adult Sprague
      Dawley rats (weighing 250-300 g). INTERVENTIONS: Intestinal ischemia/reperfusion
      was established by clamping the superior mesenteric artery for 90 mins followed
      by different reperfusion durations (2, 6, 12, 24, or 48 hrs). The sham surgical
      preparation including isolation of the superior mesenteric artery without
      occlusion was performed as control. MEASUREMENTS AND MAIN RESULTS: In comparison
      with sham control, intestinal ischemia/reperfusion caused severe intestinal
      injury, accompanied by notable cerebral damage evidenced by increased wet-to-dry
      brain weight ratio reflecting brain edema and neuronal cell apoptosis manifested
      by increased apoptotic cell number and cleaved caspase-3 protein expressions. All
      these changes were concomitant with reduced survival rates as well as impaired
      memory function determined by Morris water maze test at 24 and 48 hrs after
      reperfusion. In addition, intestinal ischemia/reperfusion resulted in significant
      increases in the levels of tumor necrosis factor-alpha and interleukin-6 both in
      the serum and in cortices and hippocampal Cornu Ammonis area 1 regions,
      concomitant with the activation of microglia, a key cellular mediator involved in
      neuroinflammation and neurodegeneration, which was evidenced by increased protein
      expressions of ionized calcium binding adaptor molecule 1. Furthermore, the
      releases of reactive oxygen species evidenced by increased malondialdehyde levels
      and decreased superoxide dismutase activities in cortices and hippocampal Cornu
      Ammonis area 1 regions were found after reperfusion. CONCLUSIONS: These findings
      indicate that intestinal ischemia/reperfusion-induced intestinal injury can lead
      to cerebral damage and memory dysfunction partly via microglia activation which
      further facilitates oxidative injury, inflammatory response, and neuronal cell
      apoptosis.

PMID- 22647412
TI  - The edge vascular response following implantation of a fully bioresorbable
      device: 'a miss always counts'.

PMID- 22647413
TI  - Amlodipine/valsartan 5/160 mg versus valsartan 160 mg in Chinese hypertensives.
AB  - BACKGROUND: A majority of hypertensives require treatment with >=2
      antihypertensive therapies to achieve blood pressure (BP) goals. Single-pill
      combinations (SPC) may improve convenience and adherence to therapy and reduce
      health care resource use and costs. The antihypertensive effects of amlodipine
      and valsartan are well established. This study evaluated the efficacy and safety
      of amlodipine/valsartan 5/160 mg SPC for the treatment of hypertension in
      predominantly Chinese patients not adequately controlled on valsartan 160 mg
      alone. METHODS: In this multicentre study (24 centres), adults with stage 1 or 2
      hypertension not adequately controlled with valsartan monotherapy were randomised
      to receive double-blind amlodipine/valsartan 5/160 mg SPC or valsartan 160 mg
      once daily for 8 weeks. RESULTS: The least-square mean change (standard error)
      from baseline to endpoint in mean sitting diastolic blood pressure (MSDBP) at
      trough, the primary efficacy variable, was -10.3 (0.39) mm Hg with
      amlodipine/valsartan and -6.6 (0.40) mm Hg with valsartan (difference: -3.7
      [0.54] mm Hg, p<0.0001). The corresponding results for mean sitting systolic
      blood pressure (MSSBP) were -14.9 (0.61) mm Hg and -7.0 (0.61) mm Hg,
      respectively (difference: -7.9 [0.84] mm Hg, p<0.0001). A significantly greater
      proportion of patients achieved overall BP control (MSSBP/MSDBP<140/90 mm Hg)
      with combination therapy (61.3%) versus monotherapy (39.3%; p<0.0001). Both
      treatments were well tolerated. CONCLUSION: Amlodipine/valsartan 5/160 mg SPC is
      a safe and effective therapy for lowering BP in predominantly Chinese adults with
      stage 1 or 2 hypertension not adequately controlled with valsartan 160 mg
      monotherapy.

PMID- 22647414
TI  - Health-related quality of life and anemia in hospitalized patients with heart
      failure.
AB  - BACKGROUND: Anemia is a serious and highly prevalent co-morbidity in chronic
      heart failure (HF) patients. Its influence on health-related quality of life (HR
      QoL) has rarely been studied, and no data is available regarding the role it
      plays in hospitalized HF patients. METHODS: Baseline data from the COACH study
      (Coordinating study evaluating Outcomes of Advising and Counselling in Heart
      Failure) were used. HR-QoL was assessed by means of generic and disease-specific
      questionnaires. Analyses were performed using ANOVA and ANCOVA, with covariates
      of age, gender, eGFR, diabetes, and NYHA class. RESULTS: In total, 1013
      hospitalized patients with a mean age of 71 (SD 11) years were included; 70% of
      these patients had no anemia (n=712), 14% had mild anemia (n=141), and 16% had
      moderate-to-severe anemia (n=160). Independent associations were found between
      anemia and physical functioning (p=0.019), anemia and role limitations due to
      physical functioning (p=0.002), anemia and general health (p=0.024), and anemia
      and global well-being (p=0.003). CONCLUSION: In addition to the burden of HF
      itself, anemia is an important factor which influences HR-QoL in hospitalized HF
      patients, and one that is most pronounced in the domain related to physical
      functioning and general health.

PMID- 22647415
TI  - Host feeding patterns of Culicoides species (Diptera: Ceratopogonidae) within the
      Picos de Europa National Park in northern Spain.
AB  - Blood meal identification can provide information about the natural host-feeding
      patterns or preferences of Culicoides species. Such information could indirectly
      provide data indicating which reservoirs are significant in associated vector
      borne diseases. We positively identified the host species through DNA sequencing
      of the cytochrome b gene in 144 of the 170 (84.7%) blood meal specimens tested.
      In the remaining samples, identification of the blood-meal source was
      unsuccessful, possibly due to the post-ingestion time prior to sampling or the
      availability of the species-specific cytochrome b gene sequences in the database.
      The majority of identified blood meals were derived from mammalian blood (95.8%),
      and only six contained chicken blood. We identified five species as mammalian
      hosts for Culicoides spp.: sheep (87.7%), human (6.5%), cattle (3.7%) and Savi's
      Pine Vole (Micrototus savii) (2.1%). The results suggested that large mammals,
      specifically ruminants, were most frequently fed upon by biting midges
      (Culicoides spp.), but evidence of opportunistic feeding behaviour was also
      found. Host feeding behaviour of Culicoides species may also be influenced by the
      relative abundance of a particular host species in the area being studied. In
      this sense, Savi's Pine Vole, a wild species, was found to be a locally relevant
      host and a putative reservoir for viruses transmitted by species of biting midges
      belonging to the Culicoides genus. Finally, feeding on multiple potential host
      species was observed. One midge acquired blood meals from human and chicken
      hosts, while four other midges fed on two different sheep.

PMID- 22647399
TI  - A multi-element psychosocial intervention for early psychosis (GET UP PIANO
      TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol
      for a pragmatic cluster randomized controlled trial.
AB  - BACKGROUND: Multi-element interventions for first-episode psychosis (FEP) are
      promising, but have mostly been conducted in non-epidemiologically representative
      samples, thereby raising the risk of underestimating the complexities involved in
      treating FEP in 'real-world' services. METHODS/DESIGN: The Psychosis early
      Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a
      larger research program (Genetics, Endophenotypes and Treatment: Understanding
      early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness
      of a multi-component psychosocial intervention versus treatment as usual (TAU) in
      a large epidemiologically based cohort of patients with FEP and their family
      members recruited from all public community mental health centers (CMHCs) located
      in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of
      Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster
      randomized controlled design. The randomized units (clusters) are the CMHCs, and
      the units of observation are the centers' patients and their family members.
      Patients in the experimental group will receive TAU plus: 1) cognitive behavioral
      therapy sessions, 2) psycho-educational sessions for family members, and 3) case
      management. Patient enrollment will take place over a 1-year period. Several
      psychopathological, psychological, functioning, and service use variables will be
      assessed at baseline and follow-up. The primary outcomes are: 1) change from
      baseline to follow-up in positive and negative symptoms' severity and subjective
      appraisal; 2) relapse occurrences between baseline and follow-up, that is,
      episodes resulting in admission and/or any case-note records of re-emergence of
      positive psychotic symptoms. The expected number of recruited patients is about
      400, and that of relatives about 300. Owing to the implementation of the
      intervention at the CMHC level, the blinding of patients, clinicians, and raters
      is not possible, but every effort will be made to preserve the independency of
      the raters. We expect that this study will generate evidence on the best
      treatments for FEP, and will identify barriers that may hinder its feasibility in
      'real-world' clinical settings, patient/family conditions that may render this
      intervention ineffective or inappropriate, and clinical, psychological,
      environmental, and service organization predictors of treatment effectiveness,
      compliance, and service satisfaction.

PMID- 22647416
TI  - Dietary patterns derived from principal component- and k-means cluster analysis:
      long-term association with coronary heart disease and stroke.
AB  - BACKGROUND AND AIMS: Studies comparing dietary patterns derived from different a
      posteriori methods in view of predicting disease risk are scarce. We aimed to
      explore differences between dietary patterns derived from principal component-
      (PCA) and k-means cluster analysis (KCA) in relation to their food group
      composition and ability to predict CHD and stroke risk. METHODS AND RESULTS: The
      study was conducted in the EPIC-NL cohort that consists of 40,011 men and women.
      Baseline dietary intake was measured using a validated food-frequency
      questionnaire. Food items were consolidated into 31 food groups. Occurrence of
      CHD and stroke was assessed through linkage with registries. After 13 years of
      follow-up, 1,843 CHD and 588 stroke cases were documented. Both PCA and KCA
      extracted a prudent pattern (high intakes of fish, high-fiber products, raw
      vegetables, wine) and a western pattern (high consumption of French fries, fast
      food, low-fiber products, other alcoholic drinks, soft drinks with sugar) with
      small variation between components and clusters. The prudent component was
      associated with a reduced risk of CHD (HR for extreme quartiles: 0.87; 95%-CI:
      0.75-1.00) and stroke (0.68; 0.53-0.88). The western component was not related to
      any outcome. The prudent cluster was related with a lower risk of CHD (0.91; 0.82
      1.00) and stroke (0.79; 0.67-0.94) compared to the western cluster. CONCLUSION:
      PCA and KCA found similar underlying patterns with comparable associations with
      CHD and stroke risk. A prudent pattern reduced the risk of CHD and stroke.

PMID- 22647417
TI  - The human MTHFR rs4846049 polymorphism increases coronary heart disease risk
      through modifying miRNA binding.
AB  - BACKGROUND AND AIMS: Abnormal functioning of 5,10-methylenetetrahydrofolate
      reductase (MTHFR) enhances the risk for coronary heart disease (CHD). Here, we
      tested whether a single-nucleotide polymorphism (SNP) located in the 3'
      untranslated region (UTR) of MTHFR was associated with CHD susceptibility by
      affecting microRNAs binding. METHODS AND RESULTS: We first analyzed in silico the
      SNPs localized in the 3' UTR of MTHFR for their ability to modify miRNA binding.
      We observed that rs4846049 (G > T) was a potential candidate SNP to modulate
      miRNAs:MTHFR mRNA complex, with the greatest changed binding free energy for has
      miR-149. Based on luciferase analysis, hsa-miR-149 inhibited the activity of the
      reporter vector carrying -T allele, but not -G allele. We further conducted a
      case-control study (654 vs 455) in a Chinese Han population. rs4846049 was
      significantly associated with increased risk for CHD. In addition, the T allele
      was associated with decreased levels of HDL-cholesterol and apoA. Finally, we
      observed a reduced MTHFR protein level in peripheral blood mononuclear cells of
      CHD patients with TT carriers compared to GG carriers of rs4846049. CONCLUSION:
      Our results suggest that rs4846049 (G > T) of MTHFR is associated with increased
      risk for CHD. We also identified a potentially pathogenetic mechanism of SNP
      modified posttranscriptional gene regulation by miRNAs to MTHFR.

PMID- 22647418
TI  - Estimation of percent body fat based on anthropometric measurements in children
      and adolescents with congenital adrenal hyperplasia due to 21-hydroxylase
      deficiency.
AB  - BACKGROUND & AIM: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
      is associated with a high risk for obesity. Anthropometric measures are simple
      and inexpensive methods to assess body fat. However, the accuracy of alternative
      methods in these patients is unknown. This study aim to develop and evaluate the
      accuracy of predictive anthropometric equations in the estimation of percent body
      fat in individuals with congenital adrenal hyperplasia due to 21-hydroxylase
      deficiency. METHODS: A total of 31 female and 22 male patients, aged 7-20 years,
      were evaluated. Dual-energy X-ray absorptiometry was used as the reference method
      for body fat, and anthropometric measurements were performed. RESULTS: Three new
      predictive equations showed similar results: Equation (1) (R2 = 0.85; SEE =
      2.89%), Equation (2) (R2 = 0.86; SEE = 2.82%), and Equation (3) (R2 = 0.86; SEE =
      2.81%). Internal cross-validation procedures showed a high R2 (range, 0.84-0.85)
      and low SEE (<3%). The limits of agreement ranged from -5.6% to 5.6% and no trend
      was observed. CONCLUSION: In children and adolescents with congenital adrenal
      hyperplasia due to 21-hydroxylase deficiency, three new predictive equations were
      validated for the estimation of percent body fat, with dual-energy X-ray
      absorptiometry as the reference method.

PMID- 22647420
TI  - Factors affecting the rate of false positive marks in CAD in full-field digital
      mammography.
AB  - OBJECTIVE: To assess the effect of breast density, fibroglandular tissue volume,
      and breast volume on the rate of false-positive marks of a computer-assisted
      detection software in digital mammography. MATERIALS AND METHODS: 222 patients
      with normal digital mammograms and a minimum follow-up of 22 months were
      retrospectively identified. MLO and CC views were analyzed using a CAD software
      with three operating points ('specific', 'balanced', 'sensitive'). False-positive
      marks were recorded. Images were analyzed by a volumetric breast density
      assessment software, yielding estimates of percentage density, fibroglandular
      tissue volume, and breast volume. Statistical analysis was performed using the
      Mann-Whitney U-test, the t-test for independent samples and the Poisson
      regression model. RESULTS: Patients with high fibroglandular tissue volumes had a
      higher mean number of false-positive mass marks than patients with low
      fibroglandular tissue volumes (specific setting: 0.50 vs. 0.35, respectively;
      balanced setting: 0.70 vs. 0.40, respectively, p<0.05; sensitive setting: 0.89
      vs. 0.58, respectively, p<0.05). Relative risk for a false-positive mass marker
      increased by 1.43 (p<0.05), 1.63 (p<0.001) and 1.50 (p<0.01) per 100ml of
      fibroglandular tissue for the specific, balanced and sensitive settings,
      respectively. No significant effects of percentage density or breast volume on
      the number or the relative risk of false-positive mass marks were observed.
      CONCLUSION: The volume of fibroglandular tissue present, but not the percentage
      density of the breast, affected the specificity for masses of the CAD software
      investigated. This may have implications for improving the performance of CAD
      systems, as the specificity of CAD may be improved by adjusting the algorithm
      threshold depending on the volume of fibroglandular tissue present. Considering
      both factors, fibroglandular tissue volume and percentage density, independently,
      could improve overall CAD performance in subgroups of patients, e.g. those with
      small, dense breasts or large breasts with low density.

PMID- 22647421
TI  - Value of contrast-enhanced sonographic micro flow imaging for prostate cancer
      detection with t-PSA level of 4-10 ng/mL.
AB  - OBJECTIVES: To compare the efficiency of contrast-enhanced ultrasonographic micro
      flow imaging (MFI) with conventional transrectal ultrasound (TRUS) in detecting
      prostate cancer with serum total prostate-specific antigen (t-PSA) of 4.0-10.0
      ng/mL. To evaluate the value of contrast-enhanced ultrasonographic MFI in
      detecting prostate cancer with t-PSA in diagnostic gray zone. METHODS: 47
      patients with t-PSA 4.0-10.0 ng/mL underwent gray scale, power Doppler TRUS and
      MFI examinations before ultrasound guided biopsies. Biopsies were performed at
      twelve sites in the base, the mid-gland and the apex of the prostate in each
      patient, when there was no abnormal ultrasound finding. When an abnormality was
      present at MFI, the biopsy specimen from the corresponding site was directed
      toward the abnormal finding. With histological results of prostate biopsy as
      reference standards, we assessed the cancer detection of these three methods.
      RESULTS: 564 specimens were collected in this study, in which 101 were prostate
      cancer confirmed histologically. 152 of 564 specimens were demonstrated abnormal
      on MFI images, in which 71 were malignant and 81 were benign confirmed
      histologically. The sensitivity, specificity, accuracy, positive predictive value
      (PPV) and negative predictive value (NPV) for MFI in detecting prostate caner
      were 70.3%, 82.5%, 80.3%, 46.7% and 92.7%, respectively. The sensitivity and NPV
      for MFI were significantly better than gray scale (38.6%, 86.9%) and power
      Doppler (32.7%, 86.0%) (P<0.001) TRUS. CONCLUSIONS: Contrast-enhanced
      ultrasonographic MFI could significantly improve the detection rate of prostate
      cancer with t-PSA in diagnostic gray zone (4-10 ng/mL) than conventional
      ultrasound.

PMID- 22647419
TI  - Normal protein anabolic response to hyperaminoacidemia in insulin-resistant
      patients with lung cancer cachexia.
AB  - BACKGROUND & AIMS: Insulin resistance of protein anabolism has been speculated to
      underlie the skeletal muscle wasting characteristic of cancer cachexia. We tested
      whether insulin resistance is present in cachectic lung cancer patients and if a
      sustained, physiological elevation of amino acids with hyperinsulinemia would
      compensate for it. METHODS: Whole-body [(13)C]leucine and [(3)H]glucose kinetics
      were assessed in 10 male non-small cell lung cancer (NSCLC) patients and 10
      healthy matched controls during a euglycemic, hyperinsulinemic clamp under
      conditions of isoaminoacidemia followed by hyperaminoacidemia. RESULTS:
      Postabsorptive glucose and protein kinetics were comparable between groups.
      Glucose uptake was significantly lower in NSCLC patients during hyperinsulinemia.
      During concurrent isoaminoacidemia, protein breakdown was suppressed in both, but
      rates were elevated in NSCLC; rates of synthesis did not change, resulting in
      reduced net protein balance (synthesis - breakdown) in response to insulin in
      NSCLC. With subsequent hyperaminoacidemia, synthesis increased significantly with
      no further change in breakdown, resulting in similar increase in net balance
      between groups. CONCLUSIONS: NSCLC patients with moderate cachexia showed
      considerable insulin resistance of glucose and of whole-body protein anabolism.
      Their anabolic protein response was stimulated normally by hyperaminoacidemia.
      Thus, ample provision of amino acids is a feasible strategy to overcome the
      protein anabolic failure of cancer cachexia.

PMID- 22647422
TI  - Medical students' skills in image interpretation before and after training: a
      comparison between 3rd-year and 6th-year students from two different medical
      curricula.
AB  - The purpose of this study was to assess student's performance in the
      interpretation of images before and after training in radiology, by comparing two
      groups, 6th-year and 3rd-year students, from two different medical curricula.
      Students participated in an anonymous evaluation consisting of the interpretation
      of 12 radiological images accompanied with the salient history and clinical data
      by answering 60 open-ended questions about technique, anatomy, semiology, and
      clinics. The number of correct, incorrect and blank responses of each group was
      used to compare pre- and post-training results. Unpaired two-sample t-test was
      used to evaluate differences between groups. A significant increase in correct
      responses was found in both groups after training. The comparison between both
      groups did not show differences for incorrect answers of the whole test and
      correct answers about anatomy in the pre-training evaluation. The percentage of
      correct answers to the median question improved from 15.5% to 53.3% for 6th-year
      students and from 8.3% to 41.1% for 3rd-year students. The post-training
      evaluation showed a significant increase of correct answers of 6th-year students
      with respect to 3rd-year students (mean +/- standard deviation 53.6 +/- 31.3% and
      38.7 +/- 29.9% respectively), mainly due to differences in technical and clinical
      questions. This study provides objective and quantitative evidence of pre- and
      post-training student skills in image interpretation. The similarities found in
      the previous level of knowledge and skills of both groups emphasizes the suitable
      change of the first-time training in radiology, from the 6th to the 3rd year
      course in medical curricula.

PMID- 22647423
TI  - Split-bolus CT-urography using dual-energy CT: feasibility, image quality and
      dose reduction.
AB  - PURPOSE: To prospectively evaluate the feasibility of dual-energy (DE) split
      bolus CT-urography (CTU) and the quality of virtual non-enhanced images (VNEI)
      and DE combined nephrographic-excretory phase images (CNEPI), and to estimate
      radiation dose reduction if true non-enhanced images (TNEI) could be omitted.
      PATIENTS AND METHODS: Between August and September 2011, 30 consecutive patients
      with confirmed or suspected urothelial cancer or with hematuria underwent DE CT.
      Single-energy TNEI and DE CNEPI were obtained. VNEI was reconstructed from CNEPI.
      Image quality of CNEPI and VNEI was evaluated using a 5-point scale. The
      attenuation of urine in the bladder on TNEI and VNEI was measured. The CT dose
      index volume (CTDI (vol)) of the two scans was recorded. RESULTS: The mean image
      quality score of CNEPI and VNEI was 4.7 and 3.3, respectively. The mean
      differences in urine attenuation between VNEI and TNEI were 14+/-15 [SD] and 
      16+/-29 in the anterior and posterior parts of the bladder, respectively. The
      mean CTDI (vol) for TNEI and CNEPI was 11.8 and 10.9 mGy, respectively. Omission
      of TNEI could reduce the total radiation dose by 52%. CONCLUSION: DE split-bolus
      CTU is technically feasible and can reduce radiation exposure; however, an
      additional TNEI scan is necessary when the VNEI quality is poor or quantitative
      evaluation of urine attenuation is required.

PMID- 22647424
TI  - Bioactive polyphenol antioxidants protect oral fibroblasts from ROS-inducing
      agents.
AB  - BACKGROUND: Oxidative damage to soft oral tissues may result from exposure to the
      chemicals or biochemicals found in teeth-whitening products, dental restorations,
      tobacco, and alcohol. Our working hypothesis is that oral tissues are susceptible
      to the toxic effects of stressors such as hydrogen peroxide (H(2)O(2)), ethanol
      (EtOH) and nicotine (Nic), which decrease cell viability/DNA synthesis and
      elevate reactive oxygen species (ROS). In this study, we investigated specific
      polyphenols and turmeric derivative antioxidants (AO) in combinations that
      counteracted the effects of these stressors on cultured oral fibroblast
      proliferation and ROS production. METHODS: Oral fibroblasts were exposed to
      stressors for 30 min and then treated with 10(-5) M of bioactive AO mixtures
      [resveratrol, ferulic acid and tetrahydrocurcuminoid (RFT), phloretin, ferulic
      acid and resveratrol (PFR), phloretin, ferulic acid and tetrahydrocurcuminoid
      (PFT)] for 24 h. Cell viability and DNA synthesis were monitored using
      incorporated 3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4
      sulphophenyl]-2H-tetrazolium (MTS) and 5-bromo-2-deoxyuridine (BrdU) assays,
      respectively. Total ROS was measured with dichlorodihydrofluorescein diacetate
      (H(2)DCFDA). RESULTS: Incubation of oral fibroblasts in the stressors for 30 min
      resulted in a dose-dependent decrease of DNA synthesis and number of viable
      cells, and an increased total ROS activity. AO treatment counteracted the insults
      by restoring DNA synthesis levels and cell viability, and decreasing the total
      ROS activity. CONCLUSION: The AO combinations of RFT, PFR and PFT protected the
      oral fibroblasts from the detrimental effects of H(2)O(2), EtOH and Nic by
      decreasing total ROS and increasing cell viability and DNA synthesis.

PMID- 22647425
TI  - Taurodontism in Brazilian patients with tooth agenesis and first and second
      degree relatives: a case-control study.
AB  - AIM: An association between tooth agenesis and taurodontism has been suggested.
      To verify if tooth agenesis and taurodontism are associated within families and
      specific patterns of tooth agenesis, this study aims to compare the frequency of
      taurodontism in patients with nonsyndromic familial tooth agenesis, their first
      and second-degree relatives with complete permanent dentition and a control group
      of unrelated healthy individuals with complete permanent dentition. MATERIALS AND
      METHODS: Panoramic radiographs of patients with nonsyndromic familial tooth
      agenesis, their first and second-degree relatives and a control group of
      individuals with complete permanent dentition were examined. Taurodontism was
      assessed on permanent mandibular first molars. The difference in the frequency of
      taurodontism among the studied groups was tested with Fisher's Exact Test.
      RESULTS: Seventeen families with nonsyndromic familial tooth agenesis were
      studied. The frequency of taurodontism was 29% in patients with tooth agenesis,
      10.3% in their first and second degree relatives, and 6.6% in the control group.
      A significant statistical difference among the studied groups was observed
      (p=0.002). Taurodontism was proportionally more frequent in patients with a
      higher number of absent teeth. It was mainly observed in patients from families
      in which the proband was diagnosed with oligodontia. CONCLUSIONS: Taurodontism is
      more frequent in nonsyndromic familial tooth agenesis. Individuals in families
      with second premolar and molar oligodontia are more likely to have taurodontism,
      even the individuals with complete dentition. This association could define a
      subphenotype for future genetic studies of dental development.

PMID- 22647426
TI  - Saliva increases the availability of lipophilic polyphenols as antioxidants and
      enhances their retention in the oral cavity.
AB  - OBJECTIVE: Lipophilic polyphenols in fruit beverages can avidly bind to surfaces
      of microorganisms and to blood cells and to impart upon them enhanced oxidant
      scavenging abilities (OSA). However, since many of the polyphenols are actually
      not fully soluble in water, they are therefore not available to act as effective
      antioxidant agents. We hypothesized that whole saliva, proteins such as albumin
      and mucin, human red blood cells and platelets, may all increase the "solubility"
      and availability of lipophilic antioxidant polyphenols thus increasing the OSA of
      whole saliva. DESIGN: The OSA of whole un-stimulated human saliva, obtained from
      healthy donors and of combinations among saliva, mucin, blood cells, fruit
      beverages and reagent polyphenols were quantified by chemiluminescence, DPPH
      radical and tetrazolium reduction assays. Kinetics of the clearance of
      polyphenols from saliva after holding in the mouth for 30s of an extract from
      beverages cinnamon was assayed by the Folin Ciocalteu's and the luminescence
      assays. RESULTS: OSA of fruit beverages and of reagent polyphenols were markedly
      increased by whole saliva, mucin and by red blood cells. Polyphenols associated
      with a cinnamon extract were retained in the oral cavity for several hours as
      measured by luminescence and Folin reagent techniques. CONCLUSIONS: A new
      approach to explain the additional role of saliva and salivary proteins and of
      blood cells as enhancers of OSA of lipophilic polyphenols is presented. This
      might have a significant importance to assess complex interactions among
      polyphenols from nutrients, salivary antioxidants, salivary proteins and blood
      cells extravasated from injure capillaries during infection and inflammation.

PMID- 22647427
TI  - Human beta-defensin 2 and protease activated receptor-2 expression in patients
      with chronic periodontitis.
AB  - OBJECTIVE: Some previous studies have shown that gingipains, trypsin-like
      proteases produced by Porphyromonas gingivalis, up-regulate human beta defensin-2
      (HBD-2) mRNA expression through protease-activated receptor-2 (PAR(2)) in
      gingival epithelial cells. This study aimed at investigating salivary HBD-2
      levels and crevicular PAR(2) mRNA expression in human chronic periodontitis and
      evaluating whether periodontal treatment affected this process. METHODS: Salivary
      and gingival crevicular fluid (GCF) samples were collected from periodontally
      healthy (control) and chronic periodontitis patients at baseline and 50 days
      after non-surgical periodontal treatment. Salivary HBD-2, and GCF TNF-alpha
      levels were analysed by ELISA, and PAR(2) mRNA at the GCF was evaluated by RT
      PCR. RESULTS: P. gingivalis was significantly (p<0.05) more prevalent in patients
      with chronic periodontitis when compared to controls. This prevalence decreased
      after periodontal therapy (p<0.0001). The control group showed statistically
      significant lower levels of HBD-2, TNF-alpha, and PAR(2) expression when compared
      to the chronic periodontitis group. In addition, periodontal treatment
      significantly reduced PAR(2) expression and HBD-2 levels in chronic periodontitis
      patients (p<0.001). CONCLUSIONS: Our results suggest that salivary HBD-2 levels
      and PAR(2) mRNA expression from GCF are higher in subjects with chronic
      periodontitis than in healthy subjects, and that periodontal treatment decreases
      both HBD-2 levels and PAR(2) expression.

PMID- 22647428
TI  - White matter brain and trigeminal nerve abnormalities in temporomandibular
      disorder.
AB  - Temporomandibular disorder (TMD) is a prevalent chronic pain disorder that
      remains poorly understood. Recent imaging studies reported functional and gray
      matter abnormalities in brain areas implicated in sensorimotor, modulatory, and
      cognitive function in TMD, but it is not known whether there are white matter
      (WM) abnormalities along the trigeminal nerve (CNV) or in the brain. Here, we
      used diffusion tensor imaging, and found that, compared to healthy controls, TMD
      patients had 1) lower fractional anisotropy (FA) in both CNVs; 2) a negative
      correlation between FA of the right CNV and pain duration; and 3) diffuse
      abnormalities in the microstructure of WM tracts related to sensory, motor,
      cognitive, and pain functions, with a highly significant focal abnormality in the
      corpus callosum. Using probabilistic tractography, we found that the corpus
      callosum in patients had a higher connection probability to the frontal pole, and
      a lower connection probability to the dorsolateral prefrontal cortex, compared to
      controls. Finally, we found that 1) FA in tracts adjacent to the ventrolateral
      prefrontal cortex and tracts coursing through the thalamus negatively correlated
      with pain intensity; 2) FA in the internal capsule negatively correlated with
      pain intensity and unpleasantness; and 3) decreases in brain FA were associated
      with increases in mean diffusivity and radial diffusivity, markers of
      inflammation and oedema. These data provide novel evidence for CNV
      microstructural abnormalities that may be caused by increased nociceptive
      activity, accompanied by abnormalities along central WM pathways in TMD.

PMID- 22647429
TI  - Differentiating between heat pain intensities: the combined effect of multiple
      autonomic parameters.
AB  - Although it is well known that pain induces changes in autonomic parameters, the
      extent to which these changes correlate with the experience of pain is under
      debate. The aim of the present study was to compare a combination of multiple
      autonomic parameters and each parameter alone in their ability to differentiate
      among 4 categories of pain intensity. Tonic heat stimuli (1minute) were
      individually adjusted to induce no pain, low, medium, and high pain in 45 healthy
      volunteers. Electrocardiogram, photoplethysmogram, and galvanic skin response
      were recorded, and the following parameters were calculated: heart rate; heart
      rate variability-high frequency (0.15 to 0.4Hz) spectral power; skin conductance
      level; number of skin conduction fluctuations; and photoplethysmographic pulse
      wave amplitude. A combination of parameters was created by fitting an ordinal
      cumulative logit model to the data and using linear coefficients of the model.
      Friedman test with post-hoc Wilcoxon test were used to compare between pain
      intensity categories for every parameter alone and for their linear combination.
      All of the parameters successfully differentiated between no pain and all other
      pain categories. However, none of the parameters differentiated between all 3
      pain categories (i.e., low and medium; medium and high; low and high). In
      contrast, the linear combination of parameters significantly differentiated not
      only between pain and no pain, but also between all pain categories (P<.001 to
      .02). These results suggest that multiparameter approaches should be further
      investigated to make progress toward reliable autonomic-based pain assessment.

PMID- 22647430
TI  - A typical working-day breakfast among children, adolescents and adults belonging
      to the middle and upper socio-economic classes in Mumbai, India - challenges and
      implications for dietary change.
AB  - OBJECTIVE: Breakfast has been linked to several aspects of health, yet breakfast
      skipping is rampant across the globe. Studies in India have focused mostly on
      children. Hence the present study examined breakfast behaviour across different
      age and gender groups. DESIGN: Cross-sectional sample, purposive sampling.
      Nutrient intakes of the participants derived from 24 h dietary recall and 3 d
      breakfast record data were compared with RDA values prescribed by the Indian
      Council of Medical Research using Student's t test, with P < 0.05 taken to
      indicate significance. SETTING: Mumbai, India. SUBJECTS: Participants (n 1027)
      aged 8 years and above. RESULTS: Nutritional adequacy of the breakfast meal and
      that of the day's diet were the main outcome measures. Eighty-one per cent of the
      participants had a nutritionally inadequate breakfast. Intakes of Fe and dietary
      fibre were notably low. Consumption of just milk or milk plus a milk food-based
      drink among schoolchildren (49 %) and increased breakfast skipping among
      adolescents (37 %) were seen. CONCLUSIONS: The study identifies both
      irregularities and/or nutritional inadequacies with respect to the breakfast
      meal. Age- and gender-specific challenges in breakfast behaviour need to be
      addressed. Development of 'nutrient-dense' breakfast foods that can be prepared
      easily, school breakfast programmes and education on the importance of breakfast
      are the needs of the hour.

PMID- 22647431
TI  - Defining cut-off values for disease activity states and improvement scores for
      patient-reported outcomes: the example of the Rheumatoid Arthritis Impact of
      Disease (RAID).
AB  - INTRODUCTION: The Rheumatoid Arthritis Impact of Disease (RAID) is a patient
      reported outcome measure evaluating the impact of rheumatoid arthritis (RA) on
      patient quality of life. It comprises 7 domains that are evaluated as continuous
      variables from 0 (best) to 10 (worst). The objective was to define and identify
      cut-off values for disease activity states as well as improvement scores in order
      to present results at the individual level (for example, patient in acceptable
      state, improved patient). METHODS: Patients with definite active RA requiring
      anti-tumour necrosis factor (anti-TNF) therapy were seen at screening, baseline
      and after 4 and 12 weeks of etanercept therapy. Answers to "Gold standard"
      questions on improvement (MCII: Minimum Clinically Important Improvement) and an
      acceptable status (PASS: Patient Acceptable Symptom State) were collected as well
      as the RAID score and Disease Activity Score 28- erythrocyte sedimentation rate
      (DAS28-ESR). Cut-offs were defined by different techniques including empirical,
      measurement error and gold standard anchors. The external validity of these cut
      offs was evaluated using the positive likelihood ratio (LR) based on the
      patient's perspective (for example, patient's global) and on low disease activity
      status (such as DAS28-ESR). RESULTS: Ninety-seven (97) of the 108 recruited
      patients (age: 54 +/- 13 years old, female gender: 75%, rheumatoid factor
      positive: 81%, disease duration: 8 +/- 7 years, CRP: 18 +/- 30 mg/l, DAS28-ESR:
      5.4 +/- 0.8) completed the 12 weeks of the study. The different techniques
      suggested thresholds ranging from 0.2 to 3 (absolute change) and from 6 to 50%
      (relative change) for defining MCII and thresholds from less than 1 to less than
      4.2 for defining PASS. The evaluation of external validity (LR+) showed the
      highest LR+ was obtained with thresholds of 3 for absolute change; 50% for
      relative change and less than 2 for an acceptable status. CONCLUSIONS: This study
      showed that thresholds defined for continuous variables are closely related to
      the methodological technique, justifying a systematic evaluation of their
      validity. Our results suggested that a change of at least 3 points (absolute) or
      50% (relative) in the RAID score should be used to define a MCII and that a
      maximal value of 2 defines an acceptable status. TRIAL REGISTRATION:
      Clinicaltrial.gov: NCT004768053.

PMID- 22647432
TI  - Comparison of antithrombotic and haemorrhagic effects of edoxaban, an oral direct
      factor Xa inhibitor, with warfarin and enoxaparin in rats.
AB  - INTRODUCTION: Factor Xa (FXa) is a key serine protease in the coagulation cascade
      and a promising target for a new antithrombotic agent. Edoxaban is an oral,
      selective and direct FXa inhibitor. The objective of this study was to compare
      the antithrombotic and haemorrhagic effects of edoxaban with clinically available
      anticoagulants, warfarin and enoxaparin, in rat models of thrombosis and
      haemorrhage. METHODS: Rats were treated with single oral administration of
      edoxaban, repeated oral dosing of warfarin for 4 days and single subcutaneous
      administration of enoxaparin before thrombosis or haemorrhage induction.
      Thrombosis was induced by the insertion of a platinum wire into the inferior vena
      cava for 60 min. Tail template bleeding time was measured after making an
      incision on the tail. RESULTS: Edoxaban at 0.3, 1 and 3mg/kg exerted dose
      dependent and significant inhibition of venous thrombus formation. The 50%
      thrombus inhibition dose (ED(50)) was 1.9 mg/kg. At supra-therapeutic doses (10
      and 20mg/kg), edoxaban significantly but moderately (less than 2-fold) prolonged
      bleeding time. Warfarin and enoxaparin also dose-dependently inhibited venous
      thrombosis and prolonged bleeding time. The ED(50) values of warfarin and
      enoxaparin were 0.12 mg/kg and 500 IU/kg, and the 2-fold bleeding time
      prolongation doses (BT2) were 0.16 mg/kg and 1700 IU/kg, respectively. The safety
      margin (ratio of BT2 to ED(50)) of edoxaban (>10.5) was greater than those of
      warfarin (1.3) and enoxaparin (3.4). CONCLUSIONS: Edoxaban inhibited venous
      thrombosis comparably to warfarin and enoxaparin, and the attendant bleeding risk
      of edoxaban was lower than that of warfarin and enoxaparin in rats.

PMID- 22647433
TI  - [Other causes of abdominal pain: acute rhabdomyolysis associated with physical
      exercise].

PMID- 22647434
TI  - Impact of frequent nocturnal hemodialysis on myocardial mechanics and
      cardiomyocyte gene expression.
AB  - BACKGROUND: Regression of left ventricular mass with nocturnal hemodialysis has
      been observed. The influence of nocturnal hemodialysis on myocardial mechanics
      and cardiomyocyte gene expression is unknown. METHODS AND RESULTS: Forty-two
      patients (30 male:12 female; age, 44 +/- 12 years [mean +/- SD]) with end-stage
      renal disease were followed for 3.1 +/- 1.8 years before and after conversion to
      nocturnal hemodialysis and were compared with 29 normal subjects (18 male:11
      female; age, 48 +/- 13 years). Myocardial mechanics were assessed by 2
      dimensional velocity vector imaging. Uremic plasma (10%) was added to cultures of
      neonatal Sprague-Dawley rat ventricular myocytes. Total RNA was isolated from
      cell cultures and subjected to differential gene expression profiling with
      specific interest in genes affecting apoptosis and fibrosis. Left ventricular
      mass index and left atrial volume index decreased from 122.6 +/- 42.6 to 98.5 +/-
      34.9 g/m(2) (P<0.001) and 25.9 +/- 9.1 to 22.5 +/- 9.6 cm(3)/m(2) (P=0.005),
      respectively. Left ventricular apical circumferential strain and basal rotation
      improved after conversion to nocturnal hemodialysis and approximated normal
      values. Nocturnal hemodialysis increased sessional dialysis dose and lowered
      parathyroid hormone levels (from 51 +/- 67 to 24 +/- 37 pmol/L, P<0.05) and
      phosphate. Under conventional hemodialysis conditions, there was an upregulation
      of genes leading to apoptosis and fibrosis in cardiomyocytes. The change in left
      ventricle rotation was associated with the change in parathyroid hormone values
      (r=0.37, P=0.02) and to the change in left ventricle mass (r=0.31, P=0.046).
      CONCLUSIONS: Frequent hemodialysis is associated with improvement in myocardial
      mechanics and cardiac gene expression profile, which warrants prognostic
      validation.

PMID- 22647436
TI  - Study on the luminescence behavior of sulfobutylether-beta-cyclodextrin with
      risperidone and its analytical application.
AB  - The interaction of sulfobutylether-beta-cyclodextrin (SBE-beta-CD) with
      risperidone (RISP) was first described with luminol-SBE-beta-CD chemiluminescence
      (CL) system by flow injection analysis (FIA). In luminol-SBE-beta-CD CL system,
      the 1:1 SBE-beta-CD...luminol(*) complexation could enhance CL intensity of
      luminol and produce the effect of complexation enhancement of CL (CEC). It was
      found that RISP could quench the CL intensity of SBE-beta-CD...luminol(*) and
      caused the effect of complexation enhancement of quenching (CEQ), the formation
      constant K(R-CD) 3.4*10(4) L mol(-1) and the stoichiometric ratio 1:1 of
      RISP...SBE-beta-CD complex were obtained by the proposed CL model. Association
      degree alpha 0.036 of RISP...SBE-beta-CD complex was also given by CL method.
      Based on the linear relationship to the decrement of luminol-SBE-beta-CD-RISP CL
      intensity and the logarithm of RISP concentration, RISP also can be quantified in
      the linear range of 3.0-500.0 nmol L(-1) with a detection limit of 1.0 nmol L(-1)
      (3sigma). The proposed method was successfully applied to monitoring excreted
      RISP in human urine. It was found that RISP reached its maximum after oral
      administration for 1.5 h with the total excretion of 14.26% within 8.5 h; the
      elimination rate constant k and half-life time t(1/2) were 0.474 and 1.5 h,
      respectively.

PMID- 22647435
TI  - Expression and biological characterization of an anti-CD20 biosimilar candidate
      antibody: a case study.
AB  - The CD20 molecule is a non-glycosylated protein expressed mainly on the surface
      of B lymphocytes. In some pathogenic B cells, it shows an increased expression,
      thus becoming an attractive target for diagnosis and therapy. Rituximab is a
      chimeric antibody that specifically recognizes the human CD20 molecule. This
      antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune
      diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this
      work, we describe the stable expression and biological evaluation of an anti-CD20
      biosimilar antibody. While rituximab is produced in fed-batch culture of
      recombinant Chinese hamster ovary (CHO) cells, our biosimilar antibody expression
      process consists of continuous culture of recombinant murine NS0 myeloma cells.
      The ability of the purified biosimilar antibody to recognize the CD20 molecule on
      human tumor cell lines, as well as on peripheral blood mononuclear cells from
      humans and primates, was demonstrated by flow cytometry. The biosimilar antibody
      induced complement-dependent cytotoxicity, antibody-dependent cell-mediated
      cytotoxicity and apoptosis on human cell lines with high expression of CD20. In
      addition, this antibody depleted CD20-positive B lymphocytes from peripheral
      blood in monkeys. These results indicate that the biological properties of the
      biosimilar antibody compare favorably with those of the innovator product, and
      that it should be evaluated in future clinical trials.

PMID- 22647437
TI  - Vibrational spectra and natural bond orbital analysis of organic crystal L
      prolinium picrate.
AB  - Vibrational spectral analysis and quantum chemical computations based on density
      functional theory (DFT) have been performed on the organic crystal L-prolinium
      picrate (LPP). The equilibrium geometry, various bonding features and harmonic
      vibrational wavenumbers of LPP have been investigated using B3LYP method. The
      calculated molecular geometry has been compared with the experimental data. The
      detailed interpretation of the vibrational spectra has been carried out with the
      aid of VEDA 4 program. The various intramolecular interactions confirming the
      biological activity of the compound have been exposed by natural bond orbital
      analysis. The distribution of Mulliken atomic charges and bending of natural
      hybrid orbitals associated with hydrogen bonding also reflects the presence of
      intramolecular hydrogen bonding thereby enhancing bioactivity. The analysis of
      the electron density of HOMO and LUMO gives an idea of the delocalization and low
      value of energy gap indicates electron transport in the molecule and thereby
      bioactivity. Vibrational analysis reveals the presence of strong O-H...O and N
      H...O interaction between L-prolinium and picrate ions providing evidence for the
      charge transfer interaction between the donor and acceptor groups and is
      responsible for its bioactivity.

PMID- 22647438
TI  - Novel salicylic acid-oriented thiourea-type receptors as colorimetric
      chemosensor: synthesis, characterizations and selective naked-eye recognition
      properties.
AB  - Based on the salicylic acid backbone, three highly sensitive and selective
      colorimetric chemosensors with an acylthiourea binding unit have been designed,
      synthesized and characterized. These chemosensors have been utilized for
      selective recognition of fluoride anions in dry DMSO solution by typical
      spectroscopic titration techniques. Furthermore, the obtained chemosensors AR1-3
      have shown naked-eye sensitivity for detection of biologically important fluoride
      ion over other anions in solution.

PMID- 22647440
TI  - Saliva samples are a viable alternative to blood samples as a source of DNA for
      high throughput genotyping.
AB  - BACKGROUND: The increasing trend for incorporation of biological sample
      collection within clinical trials requires sample collection procedures which are
      convenient and acceptable for both patients and clinicians. This study
      investigated the feasibility of using saliva-extracted DNA in comparison to blood
      derived DNA, across two genotyping platforms: Applied Biosystems TaqmanTM and
      Illumina BeadchipTM genome-wide arrays. METHOD: Patients were recruited from the
      Pharmacogenetics of Breast Cancer Chemotherapy (PGSNPS) study. Paired blood and
      saliva samples were collected from 79 study participants. The Oragene DNA Self
      Collection kit (DNAgenotek(r)) was used to collect and extract DNA from saliva.
      DNA from EDTA blood samples (median volume 8 ml) was extracted by Gen-Probe,
      Livingstone, UK. DNA yields, standard measures of DNA quality, genotype call
      rates and genotype concordance between paired, duplicated samples were assessed.
      RESULTS: Total DNA yields were lower from saliva (mean 24 MUg, range 0.2-52 MUg)
      than from blood (mean 210 MUg, range 58-577 MUg) and a 2-fold difference remained
      after adjusting for the volume of biological material collected. Protein
      contamination and DNA fragmentation measures were greater in saliva DNA. 78/79
      saliva samples yielded sufficient DNA for use on Illumina Beadchip arrays and
      using Taqman assays. Four samples were randomly selected for genotyping in
      duplicate on the Illumina Beadchip arrays. All samples were genotyped using
      Taqman assays. DNA quality, as assessed by genotype call rates and genotype
      concordance between matched pairs of DNA was high (>97%) for each measure in both
      blood and saliva-derived DNA. CONCLUSION: We conclude that DNA from saliva and
      blood samples is comparable when genotyping using either Taqman assays or genome
      wide chip arrays. Saliva sampling has the potential to increase participant
      recruitment within clinical trials, as well as reducing the resources and
      organisation required for multicentre sample collection.

PMID- 22647441
TI  - [Evaluation of thromboprophylactic therapy at Landspitali - The National
      University Hospital of Iceland; a cross-sectional study on acute wards].
AB  - OBJECTIVE: Venous thromboembolic disease is a serious and often fatal
      complication following hospital admission. Studies show that thromboprophylactic
      therapy for this condition is often underutilized. The aim of this study was to
      evaluate the performance of thromboprophylactic therapy at Landspitali - The
      University Hospital of Iceland in adult patients admitted to acute wards. METHODS
      AND MATERIALS: On 2 December 2009 hospital charts of admitted patients on acute
      wards were reviewed and assessed for appropriate thromboprophylactic treatment
      according to the 2008 guidelines from The American College of Chest Physicians.
      The results were compared to those of other countries from the multinational
      Endorse study from 2008. RESULTS: 251 patient were included of whom 47% were
      considered at risk for venous thromboembolic disease. Of those 57% received
      appropriate thromboprophylactic treatment or 78% of surgical and 26% of medical
      patients. CONCLUSIONS: Adherence to clinical guidelines for thromboprophylactic
      treatment at surgical wards of Landspitali - The National University Hospital of
      Iceland was good and well above the average compared to the results of the
      Endorse study. Performance on the medical wards was on the other hand below
      average. Our results show that application of thromoboprophylactic treatment at
      Landspitali could be improved and thereby enhance patient safety.

PMID- 22647442
TI  - [Icelandic General Practice crisis].

PMID- 22647439
TI  - Intranasal fentanyl versus intravenous morphine in the emergency department
      treatment of severe painful sickle cell crises in children: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Children with sickle cell disease (SCD) frequently and unpredictably
      present to the emergency department (ED) with pain. The painful event is the
      hallmark acute clinical manifestation of SCD, characterised by sudden onset and
      is usually bony in origin. This study aims to establish if 1.5mcg/kg of
      intranasal fentanyl (INF; administered via a Mucosal Atomiser Device, MADTM) is
      non-inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain.
      METHODS/DESIGN: This study is a randomised,double-blind, double-dummy active
      control trial of children (weighing more than 10 kg) between 1 year and 21 years
      of age with severe painful sickle cell crisis. Severe pain is defined as rated
      seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent.
      The trial will be conducted in a single tertiary urban paediatric ED in Dublin,
      Ireland. Each patient will receive a single active agent and a single placebo via
      the intravenous and intranasal routes. All clinical and research staff, patients
      and parents will be blinded to the treatment allocation. The primary endpoint is
      severity of pain scored at 10 min from administration of the study medications.
      Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and
      120 min after the administration of analgesia, proportion of patients requiring
      rescue analgesia and incidence of adverse events. The trial ends at 120 min after
      the administration of the study drugs. A clinically meaningful difference in
      validated pain scores has been defined as 13 mm. Setting the permitted threshold
      to 50% of this limit (6 mm) and assuming both treatments are on average equal, a
      sample size of 30 patients (15 per group) will provide at least 80% power to
      demonstrate that INF is non-inferior to IV morphine with a level of significance
      of 0.05. DISCUSSION: This clinical trial will inform of the role of INF 1.5mcg/kg
      via MAD in the acute treatment of severe painful sickle cell crisis in children
      in the ED setting. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67469672
      and EudraCT no. 2011-005161-20.

PMID- 22647443
TI  - [Thoughts about pension].

PMID- 22647444
TI  - [Loco-regional therapy for liver malignancy in Iceland].
AB  - BACKGROUND AND AIMS: Transarterial chemoembolization (TACE) is a loco-regional
      therapy performed to treat tumors in the liver. The branch of the hepatic artery
      supplying the tumor is catheterized and a mixture of iodized oil,
      chemotherapeutic agents and PVA embolic materials infused. TACE is a palliative
      treatment of unresectable cancer in the liver but can also be employed as
      adjunctive therapy to liver resection and/or radiofrequency ablation. The
      procedure can in certain instances downstage the disease and provide a bridge to
      liver transplantation. The aim of this study was to evaluate outcome in patients
      that have undergone loco-regional therapy in Iceland and the frequency and
      severity of complications related to the procedure. MATERIAL AND METHODS: All
      Icelandic patients that had undergone TACE, transarterial chemotherapy or bland
      embolization of liver tumors between 1 May 2007 and 1 March 2011 were included in
      the study. RESULTS: Eighteen TACE, six transarterial chemotherapy treatments and
      two bland embolizations were performed on nine patients with hepatocellular
      carcinoma (HCC), and three patients with carcinoid metastases in the liver. Mean
      survival of patients with HCC was 15.2 months. Survival of patients with
      carcinoid metastases was between 61 and 180 months. Complete response was
      achieved twice and partial response four times. The disease remained stable after
      eleven procedures but progressed after three procedures. Minor complications were
      diagnosed in 6 of 26 procedures and one major complication. No patient suffered
      from liver failure due to the procedure. Of the 9 HCC patients, 1 patient was on
      the liver transplant list before TACE and later underwent successful
      transplantation. Additionally, 3 of the remaining 8 patients were downstaged and
      put on to the transplant list.

PMID- 22647445
TI  - [Prevalence of smoking and chronic obstructive pulmonary disease among patients
      at the Akureyri Primary Care Center].
AB  - INTRODUCTION: Even though smoking has decreased significantly over the last few
      years, the majority of Icelanders 40 years of age or older have a history of
      smoking. Limited information is available on respiratory symptoms and diagnosis
      of chronic obstructive lung diseases (COPD) in this group. MATERIAL AND METHODS:
      During a four week period at the Akureyri Primary Care Center all individuals
      above the age of 40 were given a questionnaire on smoking, respiratory symptoms
      and medical treatment. There were a total of 416 individuals and the response
      rate was 63%. Spirometry was done on those who had smoked. RESULTS: Of the 259
      responders, 150 (57,9%) had a history of smoking. In this group 117 (45,2%) had
      quit but 33 (12,7%) were still smoking. Of those that had a history of smoking
      16% had COPD according to spirometry results and 2/3 did not have a previous
      diagnosis. Respiratory symptoms were more common with increasing obstruction. Of
      the smokers 26% had never been advised by a physician to stop smoking. A total of
      14,3% of the whole group had a previous diagnosis of emphysema, chronic
      obstructive pulmonary disease or chronic bronchitis. Altogether 23,5% had
      previously been diagnosed with asthma, asthmatic bronchitis or allergic
      bronchitis. CONCLUSION: A history of smoking was common among the primary care
      patients. One in six who had a smoking history were found to have COPD and the
      majority were unaware of the diagnosis. Respiratory diagnoses were common. By
      spirometric evaluation many smokers are diagnosed with previously unknown COPD.

PMID- 22647446
TI  - [Ehlers-Danlos syndrome type IV. Case study and clinical findings].
AB  - We describe Ehlers-Danlos syndrome type IV in adult patients with a confirmed
      diagnosis and a systematic review of expected clinical findings in the disease.
      Serious complications were found in four individuals, two with gastrointestinal
      perforation at the age of 32 years, two had died from an aortic rupture (34 and
      44 years old) and one has been diagnosed with aortic root dilatation. Most had
      also less severe clinical features such as varicose veins, easy bruising, thin
      and translucent skin, chronic joint subluxation or dislocation or pes planus.
      None of the females had uterine rupture or premature birth. Management and
      surveillance options were reviewed.

PMID- 22647447
TI  - Exposure to perfluorinated compounds and human semen quality in Arctic and
      European populations.
AB  - BACKGROUND: Perfluorinated compounds (PFCs) have been suspected to adversely
      affect human reproductive health. The aim of this study was to investigate the
      associations between PFC exposure and male semen quality. METHODS: PFCs were
      measured in serum from 588 partners of pregnant women from Greenland, Poland and
      Ukraine who provided a semen sample, using liquid chromatography tandem mass
      spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA),
      perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) could be
      detected in >97% of the samples. The associations between levels of these
      compounds and semen volume, sperm concentration, total sperm count, motility and
      morphology were assessed. RESULTS: Across countries, sperm concentration, total
      sperm count and semen volume were not consistently associated with PFOS, PFOA,
      PFHxS or PFNA levels. The proportion of morphologically normal cells was 35%
      lower [95% confidence interval (CI): 4-66%) for the third tertile of PFOS
      exposure as compared with the first. A similar reduction was found in relation to
      increasing PFHxS levels. At the third PFOA exposure tertile, the percentage of
      motile spermatozoa was 19% (95% CI: 1 to 39%) higher than in the first.
      CONCLUSIONS: The most robust finding in the present study was the negative
      associations between PFOS exposure and sperm morphology suggesting adverse
      effects of PFOS on semen quality, possibly due to interference with the endocrine
      activity or sperm membrane function. It cannot be excluded that this association
      and the positive association between PFOA and semen motility, which was not
      consistent across countries, might represent a chance finding due to the multiple
      statistical tests being performed.

PMID- 22647448
TI  - Uterine autotransplantation in cynomolgus macaques: the first case of pregnancy
      and delivery.
AB  - BACKGROUND: For women with congenital uterine infertility, or for those who have
      undergone hysterectomy, uterine transplantation is one of the potential
      treatments to regain fertility. In this study, we utilized a primate model of
      uterine transplantation, and evaluated the patency of our microsurgical
      anastomoses, and the perfusion of the transplanted uterus. METHODS: Two female
      cynomolgus monkeys underwent surgery. We anastomosed two arteries and one vein in
      Case 1 and two arteries and two veins in Case 2. The arteries used were the
      uterine arteries and the anastomosis was done to the external iliac artery. We
      used one of the ovarian veins in both animals, but resected the ovary from the
      Fallopian tube. Uterine arterial blood flow and uterine size were determined by
      intraoperative indocyanine green (ICG) angiography and ultrasonography. The
      biopsy of the uterine cervix was performed after surgery. RESULTS: ICG
      angiography showed that the unilateral uterine artery perfused the bilateral
      uterine bodies and cervix. In Case 1, ICG angiography showed the occlusion of one
      of the anastomosed arteries during the operation and the uterus appeared
      atrophied 2 months after operation. In Case 2, the transplanted uterus survived
      and normal menstruation occurred. The animal achieved a natural pregnancy and was
      delivered by the Caeserean section due to early separation of the placenta. The
      newborn suffered fetal distress. CONCLUSIONS: These results show the anastomosis
      of at least the bilateral uterine arteries and the unilateral ovarian vein is
      required for uterus transplantation. This is the first report of a natural
      pregnancy in a primate following uterine autotransplantation.

PMID- 22647449
TI  - Assessment of long-term function of heterotopic transplants of vitrified ovarian
      tissue in cynomolgus monkeys.
AB  - BACKGROUND: Ovarian tissue cryopreservation by rapid cooling (vitrification) is a
      convenient fertility preservation option. However, the progress of vitrified
      ovarian tissue after transplantation is not well understood in primates. METHODS:
      For tissues from cynomolgus monkeys, we used closed straw vitrification and open
      cryosupport vitrification in which tissues are immersed directly into liquid
      nitrogen. Following warming, ovarian cortical pieces were autotransplanted and
      their function was monitored by computed tomography (CT), hormone assays and
      oocyte recovery, ICSI and embryo transfers (ETs). RESULTS: Hormone cycles were
      restored in 6 of 7 animals in a mean of 126 days with no significant difference
      between the two vitrification regimens. The presence of new blood vessels
      supplying the grafted ovarian tissue was confirmed by contrast-enhanced CT.
      Oocyte retrieval from two monkeys after transplantation of the ovarian cortex
      vitrified by cryosupport vitrification yielded a total of nine oocytes of which
      six fertilized after ICSI, but ETs did not lead to any pregnancies. CONCLUSIONS:
      This work shows that CT can give insight into ovarian function after heterotopic
      transplantation, and that heterotopic autografts of vitrified ovarian cortex can
      give rise to long-term ovarian function and embryos in a primate model. It
      remains to be established how outcomes following rapid vitrification compared
      with outcomes following conventional slow cooling procedures.

PMID- 22647450
TI  - The use of follicle flushing during oocyte retrieval in assisted reproductive
      technologies: a systematic review and meta-analysis.
AB  - STUDY QUESTION: Does follicular flushing during assisted reproductive
      technologies (ART) improve the number of oocytes retrieved? SUMMARY ANSWER:
      Follicular flushing during ART does not result in a greater number of oocytes in
      normal responders. WHAT IS KNOWN ALREADY: Despite limited evidence supporting the
      use of follicular flushing, it continues to be a common procedure in many ART
      clinics. Prior studies have provided conflicting results regarding the routine
      use of flushing during oocyte retrieval. STUDY DESIGN, SIZE, DURATION: Systematic
      review and meta-analysis of 518 patients who participated in 6 randomized trials
      over 20 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Literature searches were
      conducted to retrieve randomized controlled trials on follicle or ovarian
      flushing in ART. Databases searched included PubMed, EMBASE, Web of Science and
      the Cochrane Database of Clinical Trials (CENTRAL). Six trials that included 518
      subjects matched the inclusion criteria. Studies included were limited to trials
      that were published, randomized trials comparing oocyte retrieval with a single
      lumen pick-up needle versus follicle flushing after direct aspiration with a
      multi-channel oocyte pick-up needle in ART patients. MAIN RESULTS AND THE ROLE OF
      CHANCE: In each of the trials, measures of the oocyte yield (oocytes retrieved
      divided by follicles aspirated), total oocytes retrieved, fertilization or
      pregnancy were not different when comparing direct aspiration with follicle
      flushing. Four trials reported a higher operative time with follicle flushing.
      Results of the meta-analysis indicated no significant differences in the oocytes
      retrieved [weighted mean difference: 0.07, 95% confidence interval (CI): -0.13 to
      0.29] or the oocyte yield (odds ratio: 1.06, 95% CI: 0.95-1.18) between the non
      flushing and flushing groups. LIMITATIONS, REASONS FOR CAUTION: All trials
      featured an open label design and the majority of patients in this meta-analysis
      were normal responders. The applications of these results to poor responders,
      patients undergoing natural cycle ART or minimal stimulation ART should be made
      with caution. WIDER IMPLICATIONS OF THE FINDINGS: Follicle flushing does not
      improve ART outcomes in normal-responding patients and should not be performed.
      This meta-analysis should solidify this recommendation as it includes the largest
      trial published on the subject and is consistent with a recently published
      Cochrane review. STUDY FUNDING/COMPETING INTEREST(S): This work was supported, in
      part, by the Program in Reproductive and Adult Endocrinology, NICHD, NIH,
      Bethesda, MD. The authors have no competing interests to declare. TRIAL
      REGISTRATION NUMBER: N/A.

PMID- 22647451
TI  - Safety evaluation of commonly used Chinese herbal medicines during pregnancy in
      mice.
AB  - BACKGROUND: It is unclear how safe the use of Chinese herbal medicine is during
      pregnancy and if the herbal medicines do any harm to pregnancy, embryo-fetal
      development and prenatal and post-natal growth. A large-scale preclinical study
      was conducted to detect the adverse effects of Chinese herbal medicines during
      pregnancy. METHODS: Twenty of the most commonly used Chinese herbal medicines
      prescribed for pregnancy were selected and the crude extract was administered to
      pregnant mice at clinical doses during five different gestational stages, namely
      post-implantation, gastrulation, organogenesis, maturation and whole gestation
      periods. Maternal effects on side effects, weight loss, litter reduction,
      implantation failure and fetal resorption and perinatal effects on growth
      restriction, developmental delay, congenital malformations and post-natal
      mortality were determined. RESULTS: Adverse pregnancy outcomes were commonly
      observed after maternal exposure to the herbal medicines, particularly during
      early pregnancy. Major events included maternal and perinatal mortality were
      recorded. Maternal weight gain, embryo growth and post-natal weight gain were
      significantly decreased. Fetal resorption and skeletal malformations were
      significantly increased. CONCLUSIONS: Reproductive toxicity of Chinese herbal
      medicines commonly used during pregnancy was identified in mice. Caution should
      be taken in the clinical use of herbal medicines during pregnancy.

PMID- 22647452
TI  - Higher clusterin immunolabeling and sperm DNA damage levels in hypertensive men
      compared with controls.
AB  - BACKGROUND: Clusterin, a heterodimeric glycoprotein found at several sites in the
      human male reproductive tract, could be a marker of morphologically abnormal
      spermatozoa, while TUNEL positivity indicates DNA fragmentation. Metabolic
      disorders such as diabetes mellitus and obesity may compromise sperm quality and
      fertility of men; however, little evidence specifically links hypertension with
      the impairment of male reproductive function. METHODS: By flow cytometric,
      immunofluorescence (TUNEL assay and clusterin immunolabeling) and
      immunohistochemical (peroxidase-streptavidin method) analyses, we have compared
      both clusterin- and TUNEL labeling in ejaculated spermatozoa from healthy
      normotensive donors and hypertensive subjects with the purpose to reveal possible
      differences between the two conditions. RESULTS: Data analysis from the
      normotensive (n=25) and hypertensive subjects (n=25) demonstrate a significant
      correlation between high levels of clusterin immunolabeling and the presence of
      sperm DNA damage, which is often associated with abnormal morphology. In the
      normotensive subjects, a low percentage (15.3+/-4.5) of spermatozoa positive for
      high levels of clusterin was detected; however, this percentage significantly
      increased (30.9+/-13.0) (P<0.01) in hypertensive subjects. Standard semen
      evaluations does not reveal any significant differences between the two groups of
      subjects, except for a reduced forward motility and lower sperm vitality in the
      hypertensive subjects. CONCLUSIONS: This pilot study strongly suggests a
      relationship between hypertension and markers indicative of poor sperm quality.
      In hypertensive subjects, high levels of clusterin immunolabeling identified a
      consistent fraction of ejaculated spermatozoa carrying both DNA fragmentation and
      strong morphological alterations, which was not correlated with age or with sperm
      cell mortality. The alternative possibility that sperm damage observed is due to
      adverse effects of anti-hypertensive drugs does not find support in the
      literature nor in the drug data sheets. The relationship observed between
      hypertension and human semen represents a novel and possibly relevant information
      to be considered in the study of male fertility.

PMID- 22647453
TI  - Day 3 embryo selection by metabolomic profiling of culture medium with near
      infrared spectroscopy as an adjunct to morphology: a randomized controlled trial.
AB  - STUDY QUESTION: Is the selection of a single Day 3 embryo by metabolomic
      profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct
      to morphology able to improve live birth rates in IVF, compared with embryo
      selection by morphology alone? SUMMARY ANSWER: The live birth rate after embryo
      selection by NIR spectroscopy and morphology is not significantly different
      compared with the live birth rate after embryos were selected by morphology
      alone. WHAT IS KNOWN ALREADY: The elevated incidence of pregnancy and neonatal
      problems associated with a high-twinning rate after IVF can only be successfully
      reduced by the transfer of one embryo. Current embryo assessment methods are
      unable to accurately predict the reproductive potential of an individual embryo.
      Today, a number of techniques are said to be more accurate at selecting the best
      embryo. One of these new technologies is metabolomic profiling of spent embryo
      culture media with the use of NIR spectroscopy. STUDY DESIGN, SIZE AND DURATION:
      A double-blind, randomized controlled trial was conducted between 2009 and 2011,
      and included 417 couples undergoing IVF with a single embryo transfer.
      Randomization was performed centrally just before Ovum Pick-Up (OPU), using a
      computerized randomization program. Both patient and physician were unaware of
      the treatment allocation. To ensure blinding, the allocations were placed in
      consecutively numbered, opaque envelopes. Patients were randomized (1:1) into
      either the control group (embryo selection by morphology only) or the treatment
      group (embryo selection by morphology plus NIR spectroscopy of embryo culture
      medium). PARTICIPANTS/MATERIALS, SETTING AND METHODS: At OPU, 208 patients were
      randomized to the morphology only group and 209 patients were randomized to the
      morphology plus viability score group. On Day 3, 163 patients in the control
      group and 146 patients in the treatment group met the inclusion criteria. The
      study was conducted in an academic hospital with IVF laboratory and three non
      academic hospitals. MAIN RESULTS AND THE ROLE OF CHANCE: Patient demographics and
      baseline characteristics were distributed equally over the two groups, except for
      embryo fragmentation, which was significantly higher in the treatment group. In
      the intention to treat analysis, the live birth rates were 31.7 and 26.8% for the
      control group and the treatment group, respectively (relative risk 0.84; 95%
      confidence interval 0.63-1.14, P=0.27). In the per protocol analysis, the live
      birth rates were 31.3 and 29.5% for the control group and the treatment group,
      respectively (relative risk 0.94; 95% confidence interval 0.67-1.32, P=0.73). For
      the treatment group, the embryological technician's independent choice (by
      morphology) of which embryo to transfer was recorded 138 times. In 75.4% (104 of
      138) of the transfers, the embryo with the best morphology did not have the
      highest viability score. The live birth rate of these 104 transferred embryos was
      30.8%. LIMITATIONS, REASONS FOR CAUTION: A possible limitation of our study is
      the pre-selection of all embryos by morphology and dividing the cohort of
      available embryos into two groups: good quality embryos and poor quality embryos.
      As a consequence, we have probably selected for a better prognosis patient group.
      WIDER IMPLICATIONS OF THE FINDINGS: To avoid the use of incompetent embryo
      selection tools at the expense of the patient, an evidence-based proof of
      clinical usefulness is essential before the implementation of new diagnostic
      tools in IVF laboratories. TRIAL REGISTRATION NUMBERS: Dutch Trial Registry,
      registry number NTR1178.

PMID- 22647454
TI  - The FAST study: Fertility ASsessment and advice Targeting lifestyle choices and
      behaviours: a pilot study.
AB  - BACKGROUND: Lifestyle has been shown to affect fertility in both males and
      females, with compelling evidence that smoking and being under or overweight
      impairs natural and assisted fertility, and other factors such as stress and
      caffeine have also been implicated. The objective of this study was to determine
      whether providing infertile couples with individualized lifestyle assessments and
      ongoing support facilitates positive lifestyle changes enhancing healthy
      fertility. METHODS: We conducted a prospective cohort pilot study of 23 infertile
      couples attending an Adelaide-based fertility clinic for advice and treatment
      relating to infertility. The intervention was a comprehensive assessment
      interview with the couple, focused on health and lifestyle. Motivational
      interviewing techniques were used and ongoing support provided. The assessment
      was repeated after 4 months and included an exit questionnaire. The main outcome
      measure(s) was self-reported lifestyle changes, including increased exercise,
      modified diet, reduced caffeine and alcohol consumption, ceased or reduced
      smoking and decreased psychological stress. RESULTS: Following the initial
      lifestyle assessment interview, all participants reported adverse lifestyle
      behaviour. CONCLUSIONS: The results suggest that the FAST (Fertility ASsessment
      and advice Targeting lifestyle choices and behaviours) approach of an
      individualized assessment of current lifestyle practice followed by ongoing one
      to two weekly telephone support is effective in promoting healthy lifestyle
      change. Larger studies using this methodology are now required.

PMID- 22647455
TI  - Controlled reduction for size selective synthesis of thiolate-protected gold
      nanoclusters Aun(n = 20, 24, 39, 40).
AB  - This work presents a controlled reduction method for the selective synthesis of
      different sized gold nanoclusters protected by thiolate (SR = SC2H4Ph). Starting
      with Au(III) salt, all the syntheses of Aun(SR)m nanoclusters with (n, m) = (20,
      16), (24, 20), (39, 29), and (40, 30) necessitate experimental conditions of slow
      stirring and slow reduction of Au(I) intermediate species. By controlling the
      reaction kinetics for the reduction of Au(I) into clusters by NaBH4, different
      sized gold nanoclusters are selectively obtained. Two factors are identified to
      be important for the selective growth of Au20, Au24, and Au39/40 nanoclusters,
      including the stirring speed of the Au(I) solution and the NaBH4 addition speed
      during the step of Au(I) reduction to clusters. When comparing with the synthesis
      of Au25(SC2H4Ph)18 nanoclusters, we further identified that the reduction degree
      of Au(I) by NaBH4 also plays an important role in controlling cluster size.
      Overall, our results demonstrate the feasibility of attaining new sizes of gold
      nanoclusters via a controlled reduction route.

PMID- 22647456
TI  - Effect of silymarin on bladder overactivity in cyclophosphamide-induced cystitis
      rat model.
AB  - The purpose of this study was to investigate the effects of silymarin, a
      phytotherapeutic agent, on bladder overactivity in a cyclophosphamide (CYP)
      induced cystitis rat model. Female Wistar Albino rats received a single
      intraperitoneal injection of CYP (150 mg/kg) or saline and after 72 h, bladder
      function was evaluated by in vitro preparations of whole bladders and cystometry
      with continuous saline infusion under urethane anesthesia. Silymarin or a vehicle
      was orally given for 7 days in rats. CYP was injected on the 5th day of silymarin
      or vehicle treatment and then the animals were killed on the 8th day. CYP
      treatment dramatically potentiated the basal spontaneous contractions of isolated
      whole bladders compared to control rats. In anesthetized rats, during continuous
      infusion cystometry, intercontraction interval (ICI) was significantly shorter,
      but bladder voiding pressure was not significantly changed in CYP-injected rats
      compared to control rats. In the CYP-injected group, silymarin treatment
      significantly decreased the amplitude, frequency (contractions/min) and area
      under the curve of spontaneous contractions, but failed to change carbachol
      induced contraction in isolated whole bladder. Also, silymarin treatment
      significantly increased the ICI in comparison to the vehicle treatment. In the
      saline-injected group, no significant changes in the bladder function were
      observed between the silymarin and vehicle-treated groups. Histopathological
      examination showed that CYP-induced bladder inflammation tended to be lower in
      the silymarin+CYP-treated group. In conclusion, the oral administration of
      silymarin suppressed CYP-induced bladder overactivity. Silymarin may be
      considered as an attractive treatment for CYP-induced bladder overactivity.

PMID- 22647457
TI  - Brain oscillatory complexity across the life span.
AB  - OBJECTIVE: Considering the increasing use of complexity estimates in
      neuropsychiatric populations, a normative study is critical to define the
      'normal' behaviour of brain oscillatory complexity across the life span. METHOD:
      This study examines changes in resting-state magnetoencephalogram (MEG)
      complexity - quantified with the Lempel-Ziv complexity (LZC) algorithm - due to
      age and gender in a large sample of 222 (100 males/122 females) healthy
      participants with ages ranging from 7 to 84 years. RESULTS: A significant
      quadratic (curvilinear) relationship (p<0.05) between age and complexity was
      found, with LZC maxima being reached by the sixth decade of life. Once that peak
      was crossed, complexity values slowly decreased until late senescence. Females
      exhibited higher LZC values than males, with significant differences in the
      anterior, central and posterior regions (p<0.05). CONCLUSIONS: These results
      suggest that the evolution of brain oscillatory complexity across the life span
      might be considered a new illustration of a 'normal' physiological rhythm.
      SIGNIFICANCE: Previous and forthcoming clinical studies using complexity
      estimates might be interpreted from a more complete and dynamical perspective.
      Pathologies not only cause an 'abnormal' increase or decrease of complexity
      values but they actually 'break' the 'normal' pattern of oscillatory complexity
      evolution as a function of age.

PMID- 22647459
TI  - Shivajiella indica gen. nov., sp. nov., a marine bacterium of the family
      "Cyclobacteriaceae" with nitrate reducing activity.
AB  - Novel orange pigmented, Gram-negative-staining, rod-shaped, non-motile, strictly
      aerobic strains designated NIO-S1(T) and NIO-S2 were isolated from the water
      sample of a pond adjacent to the coast and an algal mat from a fish pond,
      respectively, at Kakinada, India. Both strains were positive for oxidase,
      catalase and beta-galactosidase activities. The predominant fatty acids in NIO
      S1(T) were iso-C(15:0) (39.6%), anteiso-C(15:0) (9.9%), iso-C(17:0) 3OH (10.9%)
      and C(16:1)omega7c/C(16:1)omega6c (summed feature 3) (5.7%). The strains
      contained MK-7 as the major respiratory quinine, and diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine and three unidentified lipids as
      the polar lipids. Phylogenetic analysis indicated that strain NIO-S1(T) was a
      member of the family "Cyclobacteriaceae" of the class "Sphingobacteriia" and it
      clustered with the genera Fontibacter, Cecembia and Aquiflexum with phylogenetic
      distances of 6.8, 9.0 and 12.2% (93.2, 91.0 and 87.8% similarity), respectively.
      DNA-DNA hybridization between strains NIO-S1(T) and NIO-S2 showed a relatedness
      of 93% and rep-PCR banding patterns were similar. Based on data from the current
      polyphasic study, it is proposed that the new isolates be placed in a new genus
      and species with the name Shivajiella indica gen. nov., sp. nov. The type strain
      of Shivajiella indica is NIO-S1(T) (= KCTC 19812(T)=MTCC 11065(T)).

PMID- 22647458
TI  - A checklist for assessing the methodological quality of studies using
      transcranial magnetic stimulation to study the motor system: an international
      consensus study.
AB  - In the last decade transcranial magnetic stimulation (TMS) has been the subject
      of more than 20,000 original research articles. Despite this popularity, TMS
      responses are known to be highly variable and this variability can impact on
      interpretation of research findings. There are no guidelines regarding the
      factors that should be reported and/or controlled in TMS studies. This study
      aimed to develop a checklist to be recommended to evaluate the methodology and
      reporting of studies that use single or paired pulse TMS to study the motor
      system. A two round international web-based Delphi study was conducted.
      Panellists rated the importance of a number of subject, methodological and
      analytical factors to be reported and/or controlled in studies that use single or
      paired pulse TMS to study the motor system. Twenty-seven items for single pulse
      studies and 30 items for paired pulse studies were included in the final
      checklist. Eight items related to subjects (e.g. age, gender), 21 to methodology
      (e.g. coil type, stimulus intensity) and two to analysis (e.g. size of the
      unconditioned motor evoked potential). The checklist is recommended for inclusion
      when submitting manuscripts for publication to ensure transparency of reporting
      and could also be used to critically appraise previously published work. It is
      envisaged that factors could be added and deleted from the checklist on the basis
      of future research. Use of the TMS methodological checklist should improve the
      quality of data collection and reporting in TMS studies of the motor system.

PMID- 22647461
TI  - Use of a long acting injectable formulation of moxidectin to control the
      periparturient rise in faecal Teladorsagia circumcincta egg output of ewes.
AB  - A field study was conducted in a sheep flock in the south east of Scotland with a
      history of ivermectin resistance in Teladorsagia circumcincta. The objective of
      the study was to compare the effects of single anthelmintic treatments in ewes
      before turn-out onto pasture that was contaminated with a moderate level of
      overwintered, ivermectin resistant, T. circumcincta infective larvae. The ewes
      were treated according to label directions with either a long acting injectable
      formulation of moxidectin (1mg/kg; affording up to 14 weeks persistent action
      against macrocyclic lactone (ML)-susceptible T. circumcincta) or an oral
      formulation of moxidectin (0.2mg/kg; affording up to 5 weeks persistent action
      against ML-susceptible T. circumcincta). The lambs were enrolled in the normal
      management of the farm, and received a total of three oral ivermectin treatments
      during the 16 week study. The efficacy of both treatment strategies in
      controlling the periparturient rise in faecal nematode worm egg counts and
      subsequent pasture contamination was assessed from the faecal worm egg counts of
      the ewes and their lambs between lambing and weaning. Ewes that were treated with
      the oral formulation of moxidectin shed approximately 3.5 times more T.
      circumcincta eggs between lambing and weaning than ewes that were treated with
      the long acting formulation of moxidectin. This difference was reflected in the
      faecal worm egg counts of the lambs that were grazed alongside the different
      treatment groups of ewes. The results of the current study demonstrate persistent
      efficacy of the long acting formulation of moxidectin against an ivermectin
      resistant T. circumcincta population. The decreased pasture contamination after
      treatment could lead to improved lamb growth and a need for fewer anthelmintic
      treatments, thus potentially reducing one possible selection pressure for
      anthelmintic resistance. However, treatment with the long acting formulation of
      moxidectin would give rise to fewer susceptible nematodes being present in
      refugia, which could increase another possible selection pressure for
      anthelmintic resistance, depending on the subsequent grazing management of that
      pasture. The rationale for use of a persistent anthelmintic drug to control the
      periparturient rise in faecal ML-resistant T. circumcincta egg output of the ewes
      is discussed and potential differences in selection for macrocyclic lactone
      anthelmintic resistance using the different formulations of moxidectin are
      acknowledged.

PMID- 22647460
TI  - HER2 expression in Brazilian patients with estrogen and progesterone receptor
      negative breast carcinoma.
AB  - The aim of the study was to evaluate the relationship between clinical and
      pathological factors and survival in patients with double negative HER2
      overexpressing carcinoma and triple negative carcinoma. One hundred and sixty-one
      (161) patients diagnosed with breast cancer negative for estrogen receptor (ER)
      and progesterone receptor (PR) were included. Of the total, 58 patients had
      double negative HER2-overexpressing (ER/PR-negative and HER2-positive) and 103
      had triple negative (ER-negative, PR-negative and HER2-negative). ER and PR
      expression was assessed through immunohistochemistry (IHC) and HER2 expression
      was measured by immunohistochemistry and Fluorescent in situ Hybridization (FISH)
      analysis in tissue microarray. More than 80% had stages II and III disease and
      histologic grade III and nuclear grade 3. Patients with triple negative breast
      carcinoma had undifferentiated histologic types in 11% of cases and vascular
      invasion in 14.5%. Both groups had more than 50% visceral metastases. HER2
      expression (p=0.42) and vascular invasion (p=0.05) did not interfere with
      survival. Survival of patients with Stages I-II disease was significantly longer
      than in those with Stage III disease both for double negative HER2-overexpressing
      carcinomas (p<0.0001) and triple negative carcinomas (p=0.03). The study shows
      that hormone receptor-negative breast carcinomas were undifferentiated and
      diagnosed at advanced stages and that HER2 expression was not associated with
      overall survival.

PMID- 22647462
TI  - Tolerance to low temperatures of Toxocara cati larvae in chicken muscle tissue.
AB  - Infectivity of Toxocara cati larvae in muscle tissue of chickens after storage at
      4 degrees C and -25 degrees C was assessed in a mouse bioassay to provide
      information on the risk of meat-borne toxocarosis. Muscle tissue samples of 30
      day old T. cati infections were stored at 4 degrees C for 14 and 28 days and at 
      25 degrees C for 12, 24 and 48 h, whereafter, larvae were released by digestion.
      For each experimental group, the released larvae were inoculated in six mice.
      After 15 days, mice were euthanized and larval burden was assessed by digestion.
      In the control group (no storage of the infected chicken meat), 47.9% of the
      inoculated larvae established in mice, whereas storage of meat at 4 degrees C for
      14 days or 28 days reduced the recovery to 24.1% or 3.3%, respectively. Muscle
      larvae exposed to -25 degrees C for 12, 24 or 48h did not establish in the mice.
      The observation that larvae retain infective after refrigeration at exposure in 4
      degrees C for 28 days, emphasize the zoonotic potential of poultry meat as a
      causative agent of human toxocarosis.

PMID- 22647463
TI  - Survey of pyrethroid and organophosphate resistance in Brazilian field
      populations of Rhipicephalus (Boophilus) microplus: detection of C190A mutation
      in domain II of the para-type sodium channel gene.
AB  - The cattle tick Rhipicephalus (Boophilus) microplus causes expressive damage to
      livestock in Brazil and other countries. Its control is becoming more difficult
      due to the development of resistance in populations. Early detection of
      resistance can help in developing effective control strategies. This study
      evaluated the susceptibility of R. microplus to cypermethrin and chlorpyriphos
      and was the first attempt to identify the mechanism of resistance (target site
      insensitivity) in cattle tick populations from Minas Gerais state (Southeastern
      Brazil). Engorged female ticks were collected from 10 ranches within the state of
      Minas Gerais, and susceptibility was evaluated with the larval packet test (LPT)
      using technical grade cypermethrin and chlorpyriphos. It was possible to analyze
      LPT results of seven populations. Target site insensitivity was investigated in
      all 10 isolates by using molecular approaches for detection of the T2134A
      substitution within the domain III S6 segment and the C190A in the domain II S4-5
      linker from the para-type sodium channel gene. LPT showed that all seven
      populations were resistant to cypermethrin with resistance ratio (RR) ranging
      from 16.0 to 25.0 and 85.7% were resistant to chlorpyriphos (RR=2.2-15.6).
      Although the T2134A mutation was not detected, the C190A mutation was highly
      prevalent, being present in 82-100% of the alleles sampled in field populations.
      A significant correlation was found between the LC50 values for cypermethrin and
      the frequency of the C190A mutation suggesting that it might be responsible for
      the phenotypic resistance detected.

PMID- 22647464
TI  - Phylogenetic analysis of benign Theileria species based on major piroplasm
      surface protein (MPSP) genes from ticks of grazing cattle in Korea.
AB  - Complete major piroplasm surface protein (MPSP) gene sequences of benign
      Theileria parasites were isolated from ticks of grazing cattle in Korea. A total
      of 556 tick samples were collected in five provinces: Chungbuk, Jeonbuk, Jeonnam,
      Gyeongbuk, and Jeju during 2010-2011. Fifteen samples from Chungbuk and Jeonnam
      were positive for the Theileria MPSP gene by PCR amplification using a specific
      primer set. A phylogenetic tree was constructed with the amplified gene sequences
      and 26 additional sequences published in GenBank. The benign Theileria parasites
      were classified into eight types, those isolated from Korean cattle ticks
      belonged to Types 1 (Ikeda), 2 (Chitose), 4, and 8. Types 2 and 4 were the most
      common types, with the rate of 40%, followed by Types 1 and 8 (with the rate of
      13% and 7%, respectively). Nucleotide sequence identities of 23 theilerial MPSP
      sequences (15 MPSP gene sequences amplified and 8 sequences published) ranged
      from 67.3 to 99.8%. Multiple alignments of the deduced amino acid sequences also
      showed that each type was characterized by specific amino acids: 7 for Type 1, 9
      for Type 2, 4 for Type 4, and 3 for Type 8.

PMID- 22647465
TI  - Assessing resistance against macrocyclic lactones in gastro-intestinal nematodes
      in cattle using the faecal egg count reduction test and the controlled efficacy
      test.
AB  - The main objective of the present study was to evaluate the accuracy of the
      faecal egg count reduction test (FECRT) to assess the resistance status of
      ivermectin (IVM)-resistant isolates of the cattle nematodes Ostertagia ostertagi
      and Cooperia oncophora, using the controlled efficacy test (worm counts) as a
      reference. The second objective was to investigate whether both IVM-resistant
      isolates showed side-resistance against moxidectin (MOX) under controlled
      conditions. Thirty male Holstein calves were experimentally infected with 25,000
      L3 of an IVM-resistant O. ostertagi isolate and 25,000 L3 of an IVM-resistant C.
      oncophora isolate. Twenty-eight days later the calves were randomly divided into
      2 treatment groups and 1 untreated control group. Animals in groups 1 and 2
      received MOX (Cydectin((r)) 1%, Pfizer) and IVM (Ivomec((r)) 1%, Merial)
      respectively, by subcutaneous injection at a dose rate of 0.2mg/kg bodyweight.
      Faecal samples were collected 7 and 14 days after treatment and animals were
      necropsied 14/15 days post-treatment. Both the FECRT and the controlled efficacy
      test demonstrated that the O. ostertagi and C. oncophora isolates were resistant
      against IVM, with efficacies below 90%. The IVM-resistant O. ostertagia isolate
      was still susceptible to MOX treatment, as shown by over 99% reduction in egg
      counts and worm burden. The FECRT suggested borderline resistance against MOX in
      the IVM-resistant C. oncophora isolate, with egg count reductions between 97%
      (95% CI: 76; 100) at day 7 and 86% (95% CI: 49; 96) at day 14. However, the
      controlled efficacy test clearly showed MOX-resistance, with a decrease of only
      31% (95% CI: -12; 57) in C. oncophora worm numbers. After MOX treatment, a
      significantly lower number of eggs per female C. oncophora worms was counted
      compared to the control group (43% reduction). Due to this reduced fecundity, the
      FECRT may fail to detect MOX-resistance.

PMID- 22647466
TI  - Species and sexual differences in behavioural responses of a specialist and
      generalist parasitoid species to host-related volatiles.
AB  - The relationship between the degree of specialization of parasitoids and their
      responses to host-related volatiles is an important and current evolutionary
      question. Specialist parasitoids which have evolved to attack fewer host species
      are predicted to be more responsive to host-related volatiles than generalists.
      We tested the above prediction by comparing behavioural responses of both sexes
      of two parasitoids (Hymenoptera: Braconidae) with different degrees of host
      specificity, Microplitis croceipes (Cresson) (specialist) and Cotesia
      marginiventris (generalist), to different suites of synthetic host-related
      volatile compounds. The compounds tested at two doses (1 and 100 MUg) include two
      green leaf volatiles (GLVs: hexanal and (Z)-3-hexen-1-ol) and four herbivore
      induced plant volatiles (HIPVs: (Z)-3-hexenyl acetate, linalool, (Z)-3-hexenyl
      butyrate and (E,E)-alpha-farnesene). Two hypotheses were tested: (i) M. croceipes
      (specialist) would show relatively greater behavioural responses to the HIPVs,
      whereas C. marginiventris (generalist) would show greater behavioural responses
      to the GLVs, and (ii) females of both species would show greater responses than
      conspecific males to the host-related volatiles. At the low dose (1 MUg), females
      of the specialist showed significantly greater responses than females of the
      generalist to three of the tested HIPVs, (Z)-3-hexenyl acetate, linalool and (Z)
      3-hexenyl butyrate. In contrast, females of the generalist showed relatively
      greater responses to the GLVs. The same trends were recorded at the high dose but
      fewer significant differences were detected. In general, similar results were
      recorded for males, with the exception of linalool (an HIPV) which elicited
      significantly greater response in the generalist than the specialist. Comparing
      the sexes, females of both species showed greater responses than conspecific
      males to most of the tested volatiles. The ecological significance of these
      findings is discussed.

PMID- 22647467
TI  - [Regulation of sleep and wakefulness through the monoaminergic and cholinergic
      systems].
AB  - Sleep and wakefulness are regulated in the brainstem and hypothalamus. Classical
      brain dissecting or stimulating studies have proposed the concept of an ascending
      reticular activating system, presently known as the wakefulness center, located
      in the caudal midbrain/rostral pontine (mesopontine) areas, comprising the
      serotonergic, noradrenergic and cholinergic neural populations. These neural
      groups, in association with the histaminergic and orexinergic neurons in the
      hypothalamus, activate the cerebral the cortex through the thalamus or basal
      forebrain. This activating (waking) system is controlled by the slow wave sleep
      (SWS) generating system in the preoptic area, which receives inhibitory signals
      from the waking center. The mesopontine area is also involved in the regulation
      of rapid eye movement (REM) sleep. Reciprocal interactions between the
      cholinergic/glutamatergic excitatory systems and the aminergic/GABAergic
      inhibitory systems are crucial for the regulation of REM sleep. In the REM
      activating system, mutual excitatory interactions between cholinergic and
      glutamatergic neurons serve to maintain the state of REM sleep. The REM
      activating system in the mesopontine area receives GABAergic inhibitory signals
      from several neural groups in the periaqueductal gray and the medulla. Thus,
      sleep and wakefulness are controlled by the interplay of various neural
      populations located in several areas in the central nervous system.

PMID- 22647468
TI  - [Recent progress of neuroimaging studies on sleeping brain].
AB  - Although sleep is a familiar phenomenon, its functions are yet to be elucidated.
      Understanding these functions of sleep is an important focus area in
      neuroscience. Electroencephalography (EEG) has been the predominantly used method
      in human sleep research but does not provide detailed spatial information about
      brain activation during sleep. To supplement the spatial information provided by
      this method, researchers have started using a combination of EEG and various
      advanced neuroimaging techniques that have been recently developed, including
      positron emission tomography (PET) and magnetic resonance imaging (MRI). In this
      paper, we will review the recent progress in sleep studies, especially studies
      that have used such advanced neuroimaging techniques. First, we will briefly
      introduce several neuroimaging techniques available for use in sleep studies.
      Next, we will review the spatiotemporal brain activation patterns during non
      rapid eye movement (NREM) and rapid eye movement (REM) sleep, the dynamics of
      functional connectivity during sleep, and the consolidation of learning and
      memory during sleep; studies on the neural correlates of dreams, which have not
      yet been identified, will also be discussed. Lastly, possible directions for
      future research in this area will be discussed.

PMID- 22647469
TI  - [Sleep-wake regulation by prostaglandin D2 and adenosine].
AB  - Prostaglandin (PG) D2 and adenosine are potent endogenous somnogens that
      accumulate in the brain during prolonged wakefulness. Lipocalin-type PGD synthase
      (L-PGDS) catalyzes the isomerization of PGH2, a common precursor of various
      prostanoids, to produce PGD2. L-PGDS is localized in the leptomeninges, choroid
      plexus, and oligodendrocytes of the central nervous system. PGD2 stimulates DP1
      receptors localized in the basal forebrain and increases the local extracellular
      concentration of adenosine, a paracrine signaling molecule, to promote sleep.
      Adenosine activates adenosine A2A receptor-expressing neurons in the basal
      forebrain and ventrolateral preoptic area (VLPO) and inhibits adenosine A1
      receptor-possessing arousal neurons. Sleep-promoting neurons in the VLPO send
      inhibitory signals to suppress the histaminergic neurons in the tuberomammillary
      nucleus (TMN); the histaminergic neurons contribute to arousal through histamine
      H1 receptors. GABAergic inhibition of TMN is involved in the induction of non
      rapid eye movement (non-REM) sleep by PGD2 and adenosine A2A agonists. The neural
      network between the VLPO and TMN is considered to play a key role in regulation
      of vigilance states. Administering an L-PGD inhibitor (SeCl4), DP1 antagonist
      (ONO-4127Na), or adenosine A2A receptor antagonist (caffeine) suppresses both non
      REM and REM sleep, indicating that the PGD2-adenosine system is crucial for
      maintaining physiological sleep. Selective gene-deletion strategies based on
      Cre/loxP technology and focal RNA interference have been used for silencing the
      expression of the A2A receptor by local infection with adeno-associated virus
      carrying Cre-recombinase or short hairpin RNA. The results of these studies have
      shown that the A2Asubreceptors in the shell region of the nucleus accumbens are
      responsible for the effect of caffeine on wakefulness.

PMID- 22647470
TI  - [Hypothalamic neuropeptides implicated in the regulation of sleep/wakefulness
      states].
AB  - Several neuropeptides, including galanin, orexin, melanin-concentrating hormone
      (MCH), urocortin-2, pituitary adenylate cyclase activating protein, and
      vasoactive intestinal peptide, have been implicated in the regulation of
      sleep/wakefulness states. In particular, neuropeptides produced in the
      hypothalamus, including galanin, orexin, and MCH, have been shown to play crucial
      roles. Galanin is localized to the prepotic area of the hypothalamus and is
      likely to be involved in the promotion and maintenance of sleep. MCH, which is
      expressed by neurons in the lateral hypothalamic area (LHA), seems to be
      implicated in rapid eye movement sleep regulation. Orexins are also localized in
      the LHA and have been established as one of the most important factors in the
      regulation of sleep/wakefulness states. A series of studies have suggested that
      orexin deficiency causes narcolepsy in humans and other mammalian species,
      highlighting the roles of this hypothalamic neuropeptide in the regulation of
      sleep and wakefulness. Studies of efferent and afferent systems of orexin
      producing neurons have shown that the orexin neuronal system has close
      interactions with the systems that regulate emotion, energy homeostasis, reward,
      and arousal. These observations suggest that orexin neurons are involved in
      sensing the body's external and internal environments and regulate vigilance
      states accordingly.

PMID- 22647471
TI  - [Biological clock and sleep].
AB  - Under temporal isolation, the human sleep-wake cycle occasionally desynchronizes
      from the circadian rhythms in deep body temperature and plasma melatonin. Such
      internal desynchronization is observed even in the real world. Two distinct
      models are advanced for the sleep-wake cycle; one is a two-oscillator model and
      the other is a two-process model. However, our recent studies in human subjects
      under temporal isolation support the former model. Internal desynchronization is
      unique to the human sleep-wake cycle and has been never observed in other mammal
      species. Therefore, a specific animal model for the human sleep-wake cycle is
      needed to explore the brain mechanism. By chronic treatment with methamphetamine
      (MAP), a stimulant of the central dopaminergic system, in drinking water, rats
      showed behavioral rhythms which were independent of the circadian pacemaker in
      the suprachiasmatic nucleus (SCN), the central clock entraining to light-dark
      cycles. Furthermore, MAP treatment induces internal desynchronization between the
      MAP-induced behavioral rhythms and the circadian rhythms of clock gene expression
      in the SCN, suggesting a presence of a secondary pacemaker outside the SCN that
      regulates the sleep-wake cycle. These findings are consistent with the two
      oscillator model mentioned previously. According to the current understanding of
      the circadian system in mammals, there are a number of so-called peripheral
      clocks in the body which are regulated by the central clock in the SCN. Taking
      advantage of the MAP-induced internal desynchronization, attempts have been made
      to identity the peripheral clock(s) regulating the sleep-wake cycle. The
      nigrostriatal dopaminergic system is a possible site of the behavior-associated
      peripheral clock.

PMID- 22647472
TI  - [Circadian regulation of sleep-wake cycles and food anticipation].
AB  - The circadian clock is crucial for efficient physiological function and drives
      the temporal regulation of the sleep-wake state, metabolism, and behavior. The
      timing of food intake and the accompanying behavior are both controlled by the
      internal clock, which is located in the suprachiasmatic nucleus (SCN) of the
      anterior hypothalamus. The SCN is considered as the master clock because the
      circadian rhythms for most physiological and behavioral processes are terminated
      after SCN ablation. The molecular framework of circadian oscillations can be best
      studied in the SCN. A "core" set of circadian clock genes form autoregulatory
      transcription-translation feedback loops that are believed to drive daily rhythms
      in individual cells. These clock genes are expressed in a circadian manner not
      only in the SCN but also in other parts of the brain and many peripheral tissues.
      Mammals can anticipate a predictable daily mealtime through entrainment of
      circadian oscillators. Because the restriction of food availability to a specific
      time of the day elicits anticipatory behavior even after ablation of the SCN,
      such behaviour is assumed to be controlled by another circadian oscillator. In
      this paper, we have (1) reviewed studies involving the identification of the
      circadian clock and (2) aimed to elucidate the complex mechanism underlying
      feeding-associated rhythms by achieving a deep understanding of the circadian
      phenotypes of the SCN.

PMID- 22647473
TI  - [Neurobiology of imprinting].
AB  - Imprinting is an example of learning and memory acquisition in infancy. In the
      case of precocial birds, such as geese, ducks, and chickens, the baby birds learn
      the characteristics of the first moving object that they see within a critical
      period, and they imprint on it and follow it around. We analyzed the neural basis
      of this behavior in order to understand the neural mechanism of learning and
      memory in infancy. Information pertaining to a visual imprinting stimulus is
      recognized and processed in the visual Wulst, a region that corresponds to the
      mammalian visual cortex. It is then transmitted to the posterior region of the
      telencephalon, followed by the core region of the hyperpallium densocellulare
      (HDCo), periventricular region of the hyperpallium densocellulare (HDPe), and
      finally, the intermediate medial mesopallium (IMM), a region similar to the
      mammalian association cortex. Memory is stored in the IMM. After imprint
      training, plastic changes are observed in the visual Wulst as well as in the
      neurons of this circuit. HDCo cells, located at the center of this circuit,
      express N-methyl-D-aspartate (NMDA) receptors containing the NMDA receptor (NR)
      2B subunit; the expression of this receptor increased after the imprint training.
      Inhibition of this receptor in the cells of the HDCo region leads to failure of
      imprinting and inactivation of this circuit. Thus, NMDA receptors bearing the
      NR2B subunit play a critical role in plastic changes in this circuit and in
      induction of imprinting.

PMID- 22647474
TI  - [Can prion-like propagation occur in neurodegenerative diseases?: in view of
      transmissible systemic amyloidosis].
AB  - Common neurodegenerative diseases, including Alzheimer's disease (AD) and
      Parkinson's disease (PD), are now considered as "protein misfolding diseases,"
      because the misfolding of a small number of proteins is a key event in the
      pathogenesis and progression of these diseases. Proteins that are prone to
      misfolding and thereby associated with neurodegenerative diseases include amyloid
      beta (AD), tau (AD and tauopathy), alpha-synuclein (PD, dementia with Lewy
      bodies, etc.), polyglutamine proteins (Huntington's disease, spinocerebellar
      ataxia, etc.), and superoxide dismutase 1 (amyotrophic lateral sclerosis). These
      proteins share certain essential properties with prions. Similar to abnormal
      prions, misfolded proteins function as a template to catalyze the misfolding of
      the native proteins and assemble into insoluble, beta-sheet-rich, fibrillar
      aggregates termed as "amyloids." Furthermore, there is enough evidence supporting
      the intercellular transfer of misfolded protein aggregates. The transmission of
      these aggregates from one cell to another may be in accordance with the concept
      that neuropathological changes propagate along neuronal circuits in
      neurodegenerative diseases. Prion-like propagation mechanisms have been
      extensively analyzed in connection with systemic amyloidoses such as amyloid A
      (AA) amyloidosis and amyloid apolipoprotein AII (AApoAII) amyloidosis. Studies
      have shown that AA and AApoAII amyloidoses are transmitted from one organism to
      another through amyloid fibrils. However, studies have not yet proved that
      protein misfolding diseases, except for prion diseases, are infectious. Given the
      intercellular transfer of misfolded protein aggregates, we cannot ignore the
      possibility that disease-specific, misfolded proteins can be transmitted between
      individuals through surgical procedures or tissue transplantation. Importantly,
      cell non-autonomous mechanisms underlying the pathogenesis of neurodegenerative
      diseases may represent a more readily accessible target for novel disease
      modifying therapies. In the present review, we discuss some aspects of the prion
      like propagation of neurodegenerative diseases, taking into consideration the
      accumulated evidence supporting the transmissibility of systemic amyloidoses.

PMID- 22647475
TI  - [Are neurodegenerative diseases "protein cancers"?].
AB  - In the last 30 years, the elucidation of the molecular pathogenesis of
      neurodegenerative diseases has undergone remarkable progress, including the
      discoveries of the causative genes and risk factors of Alzheimer's disease,
      Parkinson's disease, and amyotrophic lateral sclerosis. However, the fundamental
      questions of why different neurons degenerate in different diseases and why these
      diseases are progressive have received little attention. I have proposed the
      "protein cancer" hypothesis, which states that abnormal or malignant proteins-
      such as prion proteins--generated in a cell grow and propagate from cell to cell
      by converting normal proteins, and this propagation causes disease progression,
      analogous to the metastasis of cancer cells to multiple different tissues during
      cancer progression. Intracellular filamentous inclusions composed of amyloid-like
      proteins, such as tau, alpha-synuclein, and TDP-43, are common neuropathological
      features of many neurodegenerative disorders, and the extent of the abnormal
      protein pathologies is closely related to disease progression. Recent results of
      experimental model studies as well as biochemical analyses of abnormal proteins
      in patients have provided support for this hypothesis. Therefore, small molecules
      or antibodies that can inhibit the intra- and intercellular propagation of
      abnormal proteins are expected to be promising candidates for clinical therapy.

PMID- 22647476
TI  - [Frequency of the use of vagus nerve stimulation for the treatment of intractable
      epilepsy during the first year of public health insurance coverage with in Kyushu
      Rosai Hospital and other areas in Japan].
AB  - Vagus nerve stimulation (VNS) is a palliative treatment for medically intractable
      epilepsy and has been covered by public health insurance in Japan since July 1,
      2010. The frequency of the use of VNS during the first year of insurance coverage
      was determined by assessing the number of cases for which VNS was performed in
      Kyushu Rosai Hospital, the number of registered cases, and the questionnaire
      survey filled by 68 surgeons who are board certified as both epileptologists and
      neurosurgeons. VNS devices were placed in 98 patients from July 2010 to June
      2011. These devices were placed in an average of 4.4 patients per month from July
      2010 to November 2010 and in an average of 10.9 patients from December 2010 to
      June 2011. However, we did not observe an increasing trend. Almost all of the
      surgeries were performed in the Kanto (56 patients in 8 institutes) and Tokai (24
      patients in 2 institutes) areas. VNS was not performed in many institutes
      primarily because VNS was not indicated for any of the patients. The
      questionnaire survey indicated that the use of VNS was likely to increase with an
      increase in the number of neurologists who decide on performing VNS
      preoperatively and regulate the conditions of the vagus nerve stimulator
      postoperatively. In conclusion, VNS is currently being applied in a limited
      number of institutes in the Kanto and Tokai areas, and a close association
      between the epileptologists and neurologists during preoperative and
      postoperative periods will increase the use of VNS.

PMID- 22647478
TI  - [Auditory hallucination as an initial sign of frontotemporal dementia].
AB  - A 58-year-old right-handed man presented with a 9-year history of stereotyped
      behaviors and auditory hallucinations. At 49 years of age, he began to complain
      about auditory hallucinations that said offensive things about him, and around
      the same time, he began exhibiting stereotyped behaviors. For example, he
      traveled the same long route from his office to home every evening. Disinhibitory
      behavior occurred at 53 years of age, and he was forced to retire at 54 years of
      age. After retirement, the patient stayed in bed or showed a stereotyped behavior
      of repeatedly going to a nearby shrine every day. The complaint of auditory
      hallucinations disappeared around this time. At 57 years of age, he began using a
      day service, and soon after, several stereotyped behaviors appeared in this
      setting as well. Brain magnetic resonance imaging at 59 years of age showed
      severe atrophy and knife-blade-like appearance in the bilateral temporal poles. A
      clinical diagnosis of frontotemporal dementia (FTD) was made based on the
      neurobehavioral, neuropsychological, and neuroimaging findings. FTD patients have
      been reported to show hallucinations very rarely. However, recent studies have
      reported that frontotemporal lobar degeneration (FTLD) patients with ubiquitin
      positive and transactive response-DNA-binding protein-43 (TDP-43)-positive
      pathologies (FTLD-U-TDP) and FTD patients with progranulin gene mutations often
      develop hallucinations. The current patient may belong to this group of patients
      with similar neuropathological and molecular biological bases.

PMID- 22647477
TI  - [Solitary actinomycotic brain abscess: case report].
AB  - Actinomycotic brain abscess is a rare condition with uncertain clinical features.
      Here we report the case of a 66-year-old immune-competent woman with an
      actinomycotic brain abscess who presented with sensory aphasia and mild right
      hemiparesis. She had no febrile episode or headache. Moreover, she did not have
      any periodontal or oto-rhino-laryngological disease, and the results of
      laboratory tests were normal. A computed tomography scan showed an irregular, low
      density area in the left parietal lobe. Subsequent magnetic resonance imaging
      showed low-signal intensity in a T1 weighted image, high-signal intensity in a T2
      weighted image, and mixed intensity on a diffusion weighted image. Thallium-201
      chloride scintigraphy showed definite accumulation of thallium in the lesion and
      the patient's condition gradually deteriorated. Ten days after gadolinium
      administration, a T1 weighted image showed a multi- lobulated irregular mass in
      the left parietal lobe. The patient subsequently underwent craniotomy and
      evacuation of the yellowish abscess. Gram staining of the tissue showed the
      presence of gram-positive filamentous rods, and abscess cultures were positive
      for Actinomyces and Prevotella disiens. The abscess resolved after treatment with
      a high dose of intravenous penicillin G (24 million units/day) for 8 weeks,
      followed by an oral dose of amoxicillin for 4 months. The patient was discharged
      with a rudimentary limitation of the visual field.

PMID- 22647479
TI  - Subcellular metal partitioning in larvae of the insect Chaoborus collected along
      an environmental metal exposure gradient (Cd, Cu, Ni and Zn).
AB  - Larvae of the phantom midge Chaoborus are common and widespread in lakes
      contaminated by metals derived from mining and smelting activities. To explore
      how this insect is able to cope with potentially toxic metals, we determined
      total metal concentrations and subcellular metal partitioning in final-instar
      Chaoborus punctipennis larvae collected from 12 lakes situated along gradients in
      aqueous Cd, Cu, Ni and Zn concentrations. Concentrations of the non-essential
      metals Cd and Ni were more responsive to aqueous metal gradients than were larval
      concentrations of the essential metals Cu and Zn; these latter metals were better
      regulated and exhibited only 2-3-fold increases between the least and the most
      contaminated lakes. Metal partitioning was determined by homogenization of larvae
      followed by differential centrifugation, NaOH digestion and heat denaturation
      steps so as to separate the metals into operationally defined metal-sensitive
      fractions (heat-denaturable proteins (HDP), mitochondria, and
      lysosomes/microsomes) and metal-detoxified fractions (heat stable proteins (HSP)
      and NaOH-resistant or granule-like fractions). Of these five fractions, the HSP
      fraction was the dominant metal-binding compartment for Cd, Ni and Cu. The
      proportions and concentrations of these three metals in this fraction increased
      along the metal bioaccumulation gradient, which suggests that metallothionein
      like proteins play an important role in metal tolerance of Chaoborus living in
      metal-contaminated environments. Likewise, a substantial proportion of larval Zn
      was in the HSP fraction, but its contribution did not increase progressively
      along the metal gradient. Despite the increases in Cd, Ni and Cu in the HSP
      fraction along the metal bioaccumulation gradient, some accumulation of non
      essential metals (Cd and Ni) was observed in putative metal-sensitive fractions
      (e.g., HDP, mitochondria), suggesting that metal detoxification was incomplete.
      In the case of Cd, there appears to be a threshold body concentration of about 50
      nmol Cd g(-1) dry weight, above which Cd detoxification becomes more effective
      and below which Chaoborus does not "turn on" its detoxification machinery to the
      fullest extent. We speculate that acclimation or adaptation of Chaoborus to these
      highly metal-contaminated environments may have resulted in a capacity to
      tolerate some metal spillover without comprising essential biological functions
      such as growth and reproduction.

PMID- 22647480
TI  - Small incision lenticule extraction (SMILE) versus laser in-situ keratomileusis
      (LASIK): study protocol for a randomized, non-inferiority trial.
AB  - BACKGROUND: Small incision lenticule extraction or SMILE is a novel form of
      'flapless' corneal refractive surgery that was adapted from refractive lenticule
      extraction (ReLEx). SMILE uses only one femtosecond laser to complete the
      refractive surgery, potentially reducing surgical time, side effects, and cost.
      If successful, SMILE could potentially replace the current, widely practiced
      laser in-situ keratomileusis or LASIK. The aim of this study is to evaluate
      whether SMILE is non-inferior to LASIK in terms of refractive outcomes at 3
      months post-operatively. METHODS/DESIGN: Single tertiary center, parallel group,
      single-masked, paired-eye design, non-inferiority, randomized controlled trial.
      Participants who are eligible for LASIK will be enrolled for study after informed
      consent. Each participant will be randomized to receive SMILE and LASIK in each
      eye. Our primary hypothesis (stated as null) in this non-inferiority trial would
      be that SMILE differs from LASIK in adults (>21 years old) with myopia (> -3.00
      diopter (D)) at a tertiary eye center in terms of refractive predictability at 3
      months post-operatively. Our secondary hypothesis (stated as null) in this non
      inferiority trial would be that SMILE differs from LASIK in adults (>21 years
      old) with myopia (> -3.00 D) at a tertiary eye center in terms of other
      refractive outcomes (efficacy, safety, higher-order aberrations) at 3 months post
      operatively. Our primary outcome is refractive predictability, which is one of
      several standard refractive outcomes, defined as the proportion of eyes achieving
      a postoperative spherical equivalent (SE) within +/-0.50 D of the intended
      target. Randomization will be performed using random allocation sequence
      generated by a computer with no blocks or restrictions, and implemented by
      concealing the number-coded surgery within sealed envelopes until just before the
      procedure. In this single-masked trial, subjects and their caregivers will be
      masked to the assigned treatment in each eye. DISCUSSION: This novel trial will
      provide information on whether SMILE has comparable, if not superior, refractive
      outcomes compared to the established LASIK for myopia, thus providing evidence
      for translation into clinical practice. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01216475.

PMID- 22647481
TI  - Consensus in silico computational modelling of the p22phox subunit of the NADPH
      oxidase.
AB  - The p22(phox) protein is an essential subunit of the cytochrome b(558) of the
      NADPH oxidase (Nox) complex which by generating reactive oxygen species (ROS)
      plays important role in regulating cellular function. p22(phox) stabilises the
      Nox enzyme, assists in catalytic core maturation and in the meantime provides an
      anchoring site for cytosolic regulatory subunits to bind. However, the protein
      structure of the p22(phox) is still uncertain. In this study we use an in silico
      computational bioinformatic approach to produce a consensus 3-dimensional model
      of the p22(phox). Based on published protein sequence data of human p22(phox) and
      by using transmembrane specific protein prediction algorithms, we found that
      p22(phox) consists of two domains: an N-terminal transmembrane domain (124 a.a.)
      and a C-terminal cytoplasmic domain (71 a.a.). In its predicted most stable form,
      p22(phox) contains three transmembrane helices leading to an extracellular N
      terminus and an extensive (39 a.a.) extracellular loop between helices 2 and 3.
      Furthermore, we locate the cytosolic domain phosphorylation site at
      threonine(147) which literature shows is capable of priming the p22(phox), in
      order to accept its binding partners. Our results are consistent with the
      biological characterisation of p22(phox) derived from experiments using specific
      antibody or genetic manipulation. Our 3-D protein model provides insights into
      the biological function of p22(phox) and cytochrome b(558), and can be used as
      tool to investigate the regulatory mechanism of Nox isoforms.

PMID- 22647482
TI  - Optimal BMI cut-off values for predicting diabetes, hypertension and
      hypercholesterolaemia in a multi-ethnic population.
AB  - OBJECTIVE: To determine the optimal cut-offs of BMI for Malaysian adults. DESIGN:
      Population-based, cross-sectional study. Receiver operating characteristic curves
      were used to determine the cut-off values of BMI with optimum sensitivity and
      specificity for the detection of three cardiovascular risk factors: diabetes
      mellitus, hypertension and hypercholesterolaemia. Gender-specific logistic
      regression analyses were used to examine the association between BMI and these
      cardiovascular risk factors. SETTING: All fourteen states in Malaysia. SUBJECTS:
      Malaysian adults aged >=18 years (n 32 703) who participated in the Third
      National Health and Morbidity Survey in 2006. RESULTS: The optimal BMI cut-off
      value for predicting the presence of diabetes mellitus, hypertension,
      hypercholesterolaemia or at least one of these cardiovascular risk factors varied
      from 23.3 to 24.1 kg/m2 for men and from 24.0 to 25.4 kg/m2 for women. In men and
      women, the odds ratio for having diabetes mellitus, hypertension,
      hypercholesterolaemia or at least one cardiovascular risk factor increased
      significantly as BMI cut-off point increased. CONCLUSIONS: Our findings indicate
      that BMI cut-offs of 23.0 kg/m2 in men and 24.0 kg/m2 in women are appropriate
      for classification of overweight. We suggest that these cut-offs can be used by
      health professionals to identify individuals for cardiovascular risk screening
      and weight management programmes.

PMID- 22647483
TI  - Treatment with the arginase inhibitor Nw-hydroxy-nor-L-arginine restores
      endothelial function in rat adjuvant-induced arthritis.
AB  - INTRODUCTION: Endothelial dysfunction (ED) participates to atherogenesis
      associated to rheumatoid arthritis. We recently reported increased arginase
      activity/expression in vessels from adjuvant-induced arthritis (AIA) rats. In the
      present study, we investigated the effects of a curative treatment with the
      arginase inhibitor Nw-hydroxy-nor-L-arginine (nor-NOHA) on vascular dysfunction
      in AIA rats. METHODS: AIA rats were treated with nor-NOHA (40 mg/kg/d, ip) for 21
      days after the onset of arthritis. A group of untreated AIA rats and a group of
      healthy rats served as controls. ED was assessed by the vasodilatory effect of
      acetylcholine (Ach) on aortic rings. The role of superoxide anions, prostanoids,
      endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide synthase (NOS)
      pathway was studied. Plasma levels of IL-6 and vascular endothelial growth factor
      (VEGF) were determined by ELISA kits. Arthritis severity was estimated by a
      clinical, radiological and histological analysis. RESULTS: Nor-NOHA treatment
      fully restored the aortic response to Ach to that of healthy controls. The
      results showed that this beneficial effect is mediated by an increase in NOS
      activity and EDHF and reduced superoxide anion production as well as a decrease
      in the activity of cyclooxygenase (COX)-2, thromboxane and prostacyclins
      synthases. In addition, nor-NOHA decreased IL-6 and VEGF plasma levels in AIA
      rats. By contrast, the treatment did not modify arthritis severity in AIA rats.
      CONCLUSIONS: The treatment with an arginase inhibitor has a potent effect on ED
      in AIA independently of the severity of the disease. Our results suggest that
      this new pharmacological approach has the potential as a novel add-on therapy in
      the treatment of RA.

PMID- 22647484
TI  - Overweight and obesity are increased in childhood-onset cerebrovascular disease.
AB  - The objective of this work was to determine whether overweight/obesity is a risk
      factor for cerebrovascular disease in children. The study included 53 children
      with non-neonatal-onset cerebral sinovenous thrombosis or arterial ischemic
      stroke. The prevalence of overweight/obesity was compared between this cohort and
      healthy children from the National Health and Nutrition Examination Survey. In
      addition, cerebral sinovenous thrombosis patients were compared to a group of
      matched hospitalized controls. The prevalence of overweight/obesity was
      significantly higher in the cerebral sinovenous thrombosis cohort (55%), but not
      the arterial ischemic stroke cohort (36%), relative to national controls (32%; P
      = .04 and P = .81, respectively). Similarly, the prevalence of overweight/obesity
      was significantly higher in the cerebral sinovenous thrombosis cohort than in
      Colorado controls (25%; P = .02). In conclusion, the prevalence of
      overweight/obese was significantly increased in cerebral sinovenous thrombosis
      patients as compared to both national and local controls. Results should be
      evaluated in a larger multi-institutional cohort.

PMID- 22647485
TI  - Central pontine and extrapontine myelinolysis in children: a review of 76
      patients.
AB  - This study aimed to identify the causes and contributing factors, neurologic
      presentation, and outcomes of central pontine and extrapontine myelinolysis and
      to examine any trends in the presentation and course of these disorders over the
      past 50 years. Seventy-six pediatric cases were identified in the literature.
      Age, sex, decade of diagnosis, neurologic presentation, outcome, and attributed
      causes were extracted. The results showed that the diagnosis, course, and
      outcomes of central pontine and extrapontine myelinolysis clearly have changed
      over the past few decades. Early cases generally were diagnosed at autopsy as
      opposed to computed tomography or magnetic resonance imaging more recently.
      Ninety-four percent of cases prior to 1990 and only 7% of cases from 1990 onward
      resulted in patient mortality. The decade in which the case was reported was the
      strongest predictor of outcome (P < .001), followed by sodium dysregulation (P =
      .045) and dehydration (P = .07).

PMID- 22647486
TI  - A shortcut from GPCR signaling to Rac-mediated actin cytoskeleton through an
      ELMO/DOCK complex.
AB  - Chemotaxis, chemoattractant-guided directional cell migration, plays major roles
      in human innate immunity and in development of a model organism Dictyostelium
      discoideum. Human leukocytes and D. disscoideum share remarkable similarities in
      the molecular mechanisms that control chemotaxis. These cells use G-Protein
      Coupled Receptors (GPCRs), such as chemokine receptors, to control a signaling
      network that carries out chemotactic gradient sensing and directs cell migration.
      Diverse chemokines bind to their receptors to activate small G protein Rac
      through an evolutionarily conserved mechanism. Elmo and Dock180 proteins form
      ELMO/Dock180 complexes functioning as guanine nucleotide exchange factors (GEFs)
      for Rac activation. However, the linkage between GPCR to Elmo/Dock180 for Rac
      activation that controls F-actin dynamics remained unclear. Recently, we
      discovered a novel function of an ELMO protein in Dictyostelium discoideum
      linking GPCR signaling from Gbeta to actin dynamics through regulating Rac
      activation during chemotaxis.

PMID- 22647487
TI  - MAPK14/p38alpha confers irinotecan resistance to TP53-defective cells by inducing
      survival autophagy.
AB  - Recently we have shown that the mitogen-activated protein kinase (MAPK)
      MAPK14/p38alpha is involved in resistance of colon cancer cells to camptothecin
      related drugs. Here we further investigated the cellular mechanisms involved in
      such drug resistance and showed that, in HCT116 human colorectal adenocarcinoma
      cells in which TP53 was genetically ablated (HCT116-TP53KO), overexpression of
      constitutively active MAPK14/p38alpha decreases cell sensitivity to SN-38 (the
      active metabolite of irinotecan), inhibits cell proliferation and induces
      survival-autophagy. Since autophagy is known to facilitate cancer cell resistance
      to chemotherapy and radiation treatment, we then investigated the relationship
      between MAPK14/p38alpha, autophagy and resistance to irinotecan. We demonstrated
      that induction of autophagy by SN38 is dependent on MAPK14/p38alpha activation.
      Finally, we showed that inhibition of MAPK14/p38alpha or autophagy both
      sensitizes HCT116-TP53KO cells to drug therapy. Our data proved that the two
      effects are interrelated, since the role of autophagy in drug resistance required
      the MAPK14/p38alpha. Our results highlight the existence of a new mechanism of
      resistance to camptothecin-related drugs: upon SN38 induction, MAPK14/p38alpha is
      activated and triggers survival-promoting autophagy to protect tumor cells
      against the cytotoxic effects of the drug. Colon cancer cells could thus be
      sensitized to drug therapy by inhibiting either MAPK14/p38 or autophagy.

PMID- 22647488
TI  - Back to past leeches: repeated phlebotomies and cardiovascular risk.
AB  - In patients with metabolic syndrome, body iron overload exacerbates insulin
      resistance, impairment of glucose metabolism, endothelium dysfunction and
      coronary artery responses. Conversely, iron depletion is effective to ameliorate
      glucose metabolism and dysfunctional endothelium. Most of its effectiveness seems
      to occur through the amelioration of systemic and hepatic insulin resistance. In
      a study published by BMC Medicine, Michalsen et al. demonstrated a dramatic
      improvement of blood pressure, serum glucose and lipids after removing 550 to 800
      ml of blood in subjects with metabolic syndrome. This effect was apparently
      independent of changes in insulin resistance, in contrast to previous cross
      sectional and cohort studies investigating the association between iron overload,
      insulin resistance and cardiovascular disease. Despite drawbacks in the study
      design, its findings may lead the way to investigations aimed at exploring iron
      dependent regulatory mechanisms of vascular tone in healthy individuals and
      patients with metabolic disease, thus providing a rationale for novel preventive
      and therapeutic strategies to counteract hypertension. Please see related
      article: http://www.biomedcentral.com/1741-7015/10/54.

PMID- 22647489
TI  - The use of high-frequency jet ventilation for out of operating room anesthesia.
AB  - PURPOSE OF REVIEW: High-frequency jet ventilation is a novel technique for
      providing mechanical ventilation in the out of operating room (OOR) setting. Case
      reports and a small series of patients have shown it to be useful in patients
      undergoing cardiac arrhythmia ablations, interventional radiology procedures, and
      extracorporeal shock wave lithotripsy. Recently, interest in the technique has
      grown tremendously as the ability to provide superior surgical conditions may
      lead to improved efficiency and less side-effects in a variety of procedures.
      RECENT FINDINGS: Atrial fibrillation ablation procedures, liver tumor ablations,
      and extracorporeal shock wave lithotripsy are all the procedures that benefit
      from minimal movement of the heart, liver, and kidney, respectively, during the
      procedure. Although randomized controlled trials are lacking, increasing data
      suggest that by maintaining the thoracic and abdominal structures relatively
      immobile throughout the respiratory cycle, the efficiency and safety of these
      procedures may be improved. SUMMARY: Technological advances are allowing an
      increasing number of surgical procedures to be performed in the OOR setting. Such
      procedures often depend on the precise application of ablation catheters or shock
      waves. High-frequency jet ventilation facilitates the improved accuracy of
      catheter and shock wave placement, as well as efficiency of a variety of
      procedures. Improved efficiency, with fewer side-effects, has tremendous
      implications for the growth of such procedures in the OOR setting.

PMID- 22647490
TI  - Computational genetic discoveries that could improve perioperative medicine.
AB  - PURPOSE OF REVIEW: The review examines the rationale and translational utility of
      computational genetic studies using murine models of biomedical traits. RECENT
      FINDINGS: Computational genetic mapping studies have identified the genetic basis
      for biomedical trait differences in 16 different murine models, including several
      that are of importance to perioperative medicine. SUMMARY: The results have
      generated new treatments for alleviating incisional pain and narcotic drug
      withdrawal symptoms, which are now in clinical trials. A recent study identified
      allelic differences affecting chronic pain responses in mice and humans, which
      may enable a new 'personalized' approach to treating chronic pain.

PMID- 22647491
TI  - Pediatric dermatologic procedures performed outside the operating room.
AB  - PURPOSE OF REVIEW: Pediatric dermatologic procedures performed outside of the
      operating room are often painful and frequently require general anesthesia. Laser
      procedures constitute a relatively small but significant group of the growing
      number of these encounters. This article reviews relevant dermatological
      pathophysiology, current treatment modalities and collates currently available
      evidence to inform the best practice in anesthetic care of these patients. RECENT
      FINDINGS: There is a paucity of recently published data pertaining to this group;
      most earlier studies were reported in the dermatological literature and may not
      be familiar to anesthesiologists. One very large study has reported on the safety
      of various anesthetic techniques in similar out-of-operating room circumstances.
      SUMMARY: Anesthesiologists are increasingly providing care for children
      undergoing dermatologic out-of-operating room procedures. Similar general
      considerations for out-of-operating room anesthesia equally apply to children
      undergoing these procedures. There are few recently reported data pertaining to
      this patient population and further work is needed.

PMID- 22647492
TI  - Molecular detection of respiratory viruses in immunocopromised ICU patients:
      incidence and meaning.
AB  - PURPOSE: Prospective single-center study to assess the sensitivity and clinical
      relevance of molecular testing for respiratory viruses in critically ill
      immunocompromised patients with acute respiratory failure (ARF). METHODS: 100
      consecutive critically ill immunocompromised patients with ARF in 2007-2009.
      Among them, 65 had hematologic malignancies (including 14 hematopoietic stem cell
      transplant recipients), 22 had iatrogenic immunosuppression, and 13 had solid
      malignancies. A multiplex molecular assay (MMA) was added to the usual battery of
      tests performed to look for causes of ARF. RESULTS: Nasopharyngeal aspirates
      and/or bronchoalveolar lavage fluid were tested for respiratory viruses using
      both the MMA and immunofluorescence. A virus was detected in 47 (47%) patients
      using the MMA and 8 (8%) patients using immunofluorescence (P = 0.006). MMA
      positive and MMA-negative patients had similar clinical and radiographic
      presentations and were not significantly different for the use of ventilatory
      support (58% vs. 76%, P = 0.09), occurrence of shock (43% vs. 53%, P = 0.41), use
      of renal replacement therapy (26% vs. 23%, P = 0.92), SAPS II (35 [26-44] vs. 38
      [27-50], P = 0.36), time spent in the ICU (6 vs. 7 days, P = 0.35), or ICU
      mortality (17% vs. 28%, P = 0.27). Using MMA, a virus was found in 6 of the 12
      patients with no diagnosis at the end of the etiologic investigations.
      CONCLUSIONS: In critically ill immunocompromised patients, an MMA was far more
      sensitive than immunofluorescence for respiratory virus detection. Patients with
      RVs detected in the respiratory tract had the same clinical characteristics and
      outcomes as other patients.

PMID- 22647494
TI  - Photographic assessment of burn wounds: a simple strategy in a resource-poor
      setting.
AB  - OBJECTIVE: To validate the use of photographic burn wound assessment in
      evaluation of burn size and wound characteristics. METHODS: Feasibility study of
      agreement between methods of measurement of burn size and characteristics, in
      patients admitted to the burn unit at Kamuzu Central Hospital (KCH), Malawi, over
      two months in 2011. Burn wounds were photographed and assessed clinically,
      concurrently, by an experienced clinician. Photographs reviewed by two blinded
      burn clinicians after 4-6 weeks. Correlation between clinical assessment and
      photographic evaluation was calculated using kappa score and Pearson's
      correlation coefficient. RESULTS: Thirty-nine patients were included in
      evaluation of TBSA, and fifty wounds assessed for their characteristics.
      Pearson's correlation coefficient for agreement of TBSA between clinical exam and
      photograph review by expert#1, and #2, was 0.96, 0.93 (p<0.001), respectively.
      Pearson's correlation coefficients comparing expert#1 and #2 to the gold standard
      were: proportion of full-thickness burn (0.88 and 0.81, p<0.001), and
      epithelialized superficial burn (0.89 and 0.55, p<0.001). Kappa scores were
      significant for wound evolution (expert#1 0.57, expert#2 0.64, p<0.001), and
      prognosis (expert#1 0.80, expert#2 0.80, p<0.001). CONCLUSIONS: Burn assessment
      with digital photography is a valid and affordable alternative to direct clinical
      exam, alleviating access issues to burn care in developing countries.

PMID- 22647493
TI  - Human exposure to anopheline mosquitoes occurs primarily indoors, even for users
      of insecticide-treated nets in Luangwa Valley, South-east Zambia.
AB  - BACKGROUND: Current front line malaria vector control methods such as indoor
      residual spraying (IRS) and long-lasting insecticidal nets (LLINs), rely upon the
      preference of many primary vectors to feed and/or rest inside human habitations
      where they can be targeted with domestically-applied insecticidal products. We
      studied the human biting behaviour of the malaria vector Anopheles funestus Giles
      and the potential malaria vector Anopheles quadriannulatus Theobald in Luangwa
      valley, south-east Zambia. METHODS: Mosquitoes were collected by human landing
      catch in blocks of houses with either combined use of deltamethrin-based IRS and
      LLINs or LLINs alone. Human behaviour data were collected to estimate how much
      exposure to mosquito bites indoors and outdoors occurred at various times of the
      night for LLIN users and non-users. RESULTS: Anopheles funestus and An.
      quadriannulatus did not show preference to bite either indoors or outdoors: the
      proportions [95% confidence interval] caught indoors were 0.586 [0.303, 0.821]
      and 0.624 [0.324, 0.852], respectively. However, the overwhelming majority of
      both species were caught at times when most people are indoors. The proportion of
      mosquitoes caught at a time when most people are indoors were 0.981 [0.881,
      0.997] and 0.897 [0.731, 0.965], respectively, so the proportion of human
      exposure to both species occuring indoors was high for individuals lacking LLINs
      (An. funestus: 0.983 and An. quadriannulatus: 0.970, respectively). While LLIN
      users were better protected, more than half of their exposure was nevertheless
      estimated to occur indoors (An. funestus: 0.570 and An. quadriannulatus: 0.584).
      CONCLUSIONS: The proportion of human exposure to both An. funestus and An.
      quadriannulatus occuring indoors was high in the area and hence both species
      might be responsive to further peri-domestic measures if these mosquitoes are
      susceptible to insecticidal products.

PMID- 22647495
TI  - Pulmonary microvascular hyperpermeability and expression of vascular endothelial
      growth factor in smoke inhalation- and pneumonia-induced acute lung injury.
AB  - INTRODUCTION: Acute lung injury (ALI) and sepsis are major contributors to the
      morbidity and mortality of critically ill patients. The current study was
      designed further evaluate the mechanism of pulmonary vascular hyperpermeability
      in sheep with these injuries. METHODS: Sheep were randomized to a sham-injured
      control group (n=6) or ALI/sepsis group (n=7). The sheep in the ALI/sepsis group
      received inhalation injury followed by instillation of Pseudomonas aeruginosa
      into the lungs. These groups were monitored for 24 h. Additional sheep (n=16)
      received the injury and lung tissue was harvested at different time points to
      measure lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA
      and protein expression as well as 3-nitrotyrosine protein expression in lung
      homogenates. RESULTS: The injury induced severe deterioration in pulmonary gas
      exchange, increases in lung lymph flow and protein content, and lung water
      content (P<0.01 each). These alterations were associated with elevated lung and
      plasma nitrite/nitrate concentrations, increased tracheal blood flow, and
      enhanced VEGF mRNA and protein expression in lung tissue as well as enhanced 3
      nitrotyrosine protein expression (P<0.05 each). CONCLUSIONS: This study describes
      the time course of pulmonary microvascular hyperpermeability in a clinical
      relevant large animal model and may improve the experimental design of future
      studies.

PMID- 22647496
TI  - Sleep hygiene and problem behaviors in snoring and non-snoring school-age
      children.
AB  - OBJECTIVES: The effects of sleep-disordered breathing, sleep restriction,
      dyssomnias, and parasomnias on daytime behavior in children have been previously
      assessed. However, the potential relationship(s) between sleep hygiene and
      children's daytime behavior remain to be explored. The primary goal of this study
      was to investigate the relationship between sleep hygiene and problematic
      behaviors in non-snoring and habitually snoring children. METHODS: Parents of 100
      5- to 8-year-old children who were reported to snore "frequently" to "almost
      always," and of 71 age-, gender-, and ethnicity-matched children who were
      reported to never snore participated in this study. As part of a larger, ongoing
      study, children underwent nocturnal polysomnography and parents were asked to
      complete the Children's Sleep Hygiene Scale (CSHS) and the Conners' Parent Rating
      Scales-Revised (CPRS-R:L). RESULTS: In the snoring group, strong negative
      correlations (r=-.39, p<.001) between the CSHS overall sleep hygiene score and
      the CPRS-R:L DSM-IV total scores emerged. Additionally, several subscales of the
      CSHS and CPRS-R:L were significantly correlated (p-values from <.000 to .004) in
      snoring children. No significant correlations were observed between the CSHS and
      the CPRS-R:L in the non-snoring children. CONCLUSIONS: Parental reports of
      behavioral patterns in snoring children indicate that poorer sleep hygiene is
      more likely to be associated with behavior problems, including hyperactivity,
      impulsivity, and oppositional behavior. In contrast, no significant relationships
      between sleep hygiene and problem behaviors emerged among non-snoring children.
      These results indicate that children at risk for sleep disordered breathing are
      susceptible to daytime behavior impairments when concurrently coupled with poor
      sleep hygiene practices.

PMID- 22647497
TI  - Differential effects of sleep disordered breathing on polysomnographic
      characteristics in preschool and school aged children.
AB  - OBJECTIVE: Childhood sleep disordered breathing (SDB) peaks in the preschool
      years. We aimed to compare the effects of SDB on polysomnographic characteristics
      between preschool and school aged children. PARTICIPANTS AND METHODS: One hundred
      and fifty-two preschool (3-5 y) and 105 school-aged (7-12 y) children, referred
      for assessment of SDB, plus controls (39, 3-5 y and 34, 7-12 y) with no history
      of snoring underwent overnight polysomnography. Subjects were grouped by their
      obstructive apnea hypopnea index (AHI) into those with primary snoring, mild
      obstructive sleep apnea (OSA), and moderate/severe OSA. The effects of SDB
      severity on sleep architecture and respiratory characteristics were compared
      between the age cohorts using quantile regression. RESULTS: There was an average
      reduction in median sleep efficiency of 3.5% (p=0.004) and an average increase in
      median WASO of 2% (p=0.08) between the age cohorts across the severity groups,
      with sleep efficiency falling and WASO increasing with increasing SDB severity in
      the school-aged, but not the preschool, cohort. There was an average difference
      in median central AHI of 0.6 events/h (p<0.001) between the age cohorts across
      the severity groups, with the 3-5 y old cohort but not the 7-12 y old cohort
      having more central apneas with increasing SDB severity. CONCLUSIONS: We have
      demonstrated clinically important, age-related differences in sleep architecture
      in children with SDB. Preschool children with SDB maintain sleep efficiency and
      awaken fewer times throughout the night than do school aged children with a
      comparable severity of SDB, but experience more central apneas. This may have
      implications for the outcomes and treatment of SDB in children of different ages.

PMID- 22647498
TI  - Cysteinyl leukotriene receptors in tonsillar B- and T-lymphocytes from children
      with obstructive sleep apnea.
AB  - OBJECTIVES: Cysteinyl leukotrienes have been implicated in the pathogenesis of
      adenotonsillar hypertrophy in children with obstructive sleep apnea (OSA). This
      study aimed to quantify the expression of cysteinyl leukotriene receptors
      (CysLT(1), CysLT(2)) by tonsillar lymphocyte subpopulations from children with
      OSA and to make comparisons to lymphocyte subpopulations from control subjects
      with recurrent tonsillitis (RT). METHODS: Tonsillar tissue from children with OSA
      or RT was studied for CysLT(1) and CysLT(2) expression by RT-PCR, flow cytometry
      (FC), and immunofluorescence. RESULTS: Ten children with OSA and 10 control
      subjects were recruited. In OSA participants, CysLT(1)+ fraction of small-size
      CD19+ B-lymphocytes was similar to the CysLT(1)+ CD3+ T-lymphocytes fraction (FC:
      36.5 [16.5-55.4] vs. 14 [2.8-22.1]) (p>0.05) and higher than the CysLT(1)+
      moderate/large-size CD19+ B-lymphocytes fraction (6.6 [1.5-14.4]) (p<0.01).
      Similar trends were recognized for CysLT(2). CysLT(1) and CysLT(2)
      immunoreactivity was detected by immunofluorescence in the tonsillar mantle zones
      (small B-lymphocytes) and the extrafollicular areas (T-lymphocytes). Compared to
      subjects with RT, children with OSA had significantly higher expression of
      CysLT(1) in small-size CD19+ B-lymphocytes (FC) and in CD3+ T-lymphocytes (RT-PCR
      and FC) (p<0.05). CONCLUSIONS: Increased expression of leukotriene receptors by
      immunologically active tonsillar areas in children with OSA is a potential
      therapeutic target for pediatric sleep apnea.

PMID- 22647499
TI  - Validation of an LC-ESI-MS/MS method for the quantitation of phosphodiesterase-5
      inhibitors and their main metabolites in rat serum and brain tissue samples.
AB  - This work proposes a liquid chromatography-electrospray ionization ion trap mass
      spectrometry (LC-ESI-ITMS) method, for the quantification of sildenafil (SDF),
      tadalafil (TDF) and vardenafil (VDF) and their metabolites N-desmethylSDF, O
      desethylSDF and N-desethylVDF, preceded by a sample preparation step based on
      protein and phospholipid elimination. A C8 column (150 mm * 4.6 mm, 5 MUm) with
      ammonium formate (20mM) and acetonitrile as the mobile phase components have been
      used. This method has been validated, obtaining limits of quantification ranged
      from 1 to 2.5 ng/mL and 2 to 5 ng/g in serum and brain tissue respectively, while
      limits of detection ranged from 0.3 to 0.9 ng/mL in serum and 0.6 to 1.9 ng/g in
      brain tissue. Assay recoveries for low level QC samples were higher than 83% and
      the matrix effect ranged between 91% and 108% in serum and between 98% and 107%
      in brain tissue. The method has been applied to the quantification of these
      compounds in the serum and brain tissue of rats treated intraperitoneally with 10
      mg/kg of SDF, TDF or VDF.

PMID- 22647500
TI  - Sand box experiments with bioclogging of porous media: hydraulic conductivity
      reductions.
AB  - Tracer experiments during clogging and de-clogging experiments in a 2D sand box
      were via an image analysis used to establish a data set on the relation between
      changes in hydraulic conductivity (K) and relative porosity (beta). Clogging
      appears to create a finger-like tracer transport, which could be caused by an
      initial heterogeneous distribution of biomass in the sand box. De-clogging occurs
      at a slower rate possibly due to the presence of inert biomass that is not
      affected by the starvation conditions by sudden removal of the substrate source.
      The tracer front was observed to get disturbed closer and closer to the substrate
      source during the experiments suggesting that the zone of clogging moved
      upstream. Three clogging models, K(beta), from the literature were tested for
      their ability to describe the temporal changes in clogging at the scale of the
      sand box; the model of Clement et al. (1996) that makes no assumption on biomass
      distribution, the plug formation model of Thullner et al. (2002a), and the
      biofilm-plug formation model of Vandevivere (1995). The plug formation and
      biofilm-plug formation models both match the observed changes between the
      hydraulic conductivity of the sand box and the relative porosity. Unfortunately
      our experiments did not reach low relative porosities where the two models
      predict different behaviors. The model by Clement et al. (1996) underestimates
      clogging.

PMID- 22647501
TI  - Evaluating joint-space narrowing and cartilage loss in rheumatoid arthritis by
      using MRI.
AB  - INTRODUCTION: Magnetic resonance imaging (MRI) has been shown to be superior to
      radiography (XR) for assessing synovitis, osteitis, and bone erosion in
      rheumatoid arthritis (RA), particularly in clinical trials. However, relatively
      little has been reported on the ability of MRI to evaluate articular cartilage
      loss, or joint-space narrowing (JSN), in the hands and wrists. In a previous
      study, we adapted the nine-point Genant-modified Sharp XR-JSN score for use with
      MRI (MRI-JSN). In this study, we compare MRI-JSN with XR-JSN by using images from
      two multicenter clinical trials. METHODS: Baseline XR and 1.5-Tesla MR images of
      one hand and wrist from each of 47 subjects with RA enrolled in one of two
      multicenter clinical trials were evaluated by using the XR-JSN and MRI-JSN
      methods by a single radiologist experienced in the two methods. Radiographs and
      MR images were read independently on different occasions. RESULTS: In total, 575
      of 611 joints were compared (one metacarpophalangeal joint of the thumb and 35
      proximal interphalangeal joints were outside the MRI field of view and could not
      be assessed). The 22 (47%) subjects showed JSN with both XR and MRI, and 25 (53%)
      subjects showed no JSN with either method. No subject showed JSN with only one or
      the other method. MRI showed high agreement with XR (intraclass correlation
      coefficient = 0.83). Sensitivity of MRI for JSN, by using XR as the gold
      standard, was 0.94; specificity was 0.91; accuracy was 0.91; positive predictive
      value was 0.64; and negative predictive value was 0.99. CONCLUSIONS: This
      validation exercise suggests that MRI JSN scoring may offer a viable alternative
      to XR JSN scoring in multicenter clinical trials of RA. However, the relative
      longitudinal sensitivity of MRI to change and the ability to discriminate
      therapeutic effect on JSN were not evaluated in this study.

PMID- 22647502
TI  - Environmental sustainability comparison of a hypothetical pneumatic waste
      collection system and a door-to-door system.
AB  - Waste collection is one of the life cycle phases that influence the environmental
      sustainability of waste management. Pneumatic waste collection systems represent
      a new way of arranging waste collection in densely populated urban areas.
      However, limited information is available on the environmental impacts of this
      system. In this study, we compare the environmental sustainability of
      conventional door-to-door waste collection with its hypothetical pneumatic
      alternative. Furthermore, we analyse whether the size of the hypothetical
      pneumatic system, or the number of waste fractions included, have an impact on
      the results. Environmental loads are calculated for a hypothetical pneumatic
      waste collection system modelled on an existing dense urban area in Helsinki,
      Finland, and the results are compared to those of the prevailing, container
      based, door-to-door waste collection system. The evaluation method used is the
      life-cycle inventory (LCI). In this study, we report the atmospheric emissions of
      greenhouse gases (GHG), SO(2) and NO(x). The results indicate that replacing the
      prevailing system with stationary pneumatic waste collection in an existing urban
      infrastructure would increase total air emissions. Locally, in the waste
      collection area, emissions would nonetheless diminish, as collection traffic
      decreases. While the electricity consumption of the hypothetical pneumatic system
      and the origin of electricity have a significant bearing on the results,
      emissions due to manufacturing the system's components prove decisive.

PMID- 22647503
TI  - Leaching studies for tin recovery from waste e-scrap.
AB  - Printed circuit boards (PCBs) are the most essential components of all electrical
      and electronic equipments, which contain noteworthy quantity of metals, some of
      which are toxic to life and all of which are valuable resources. Therefore,
      recycling of PCBs is necessary for the safe disposal/utilization of these metals.
      Present paper is a part of developing Indo-Korean recycling technique consists of
      organic swelling pre-treatment technique for the liberation of thin layer of
      metallic sheet and the treatment of epoxy resin to remove/recover toxic soldering
      material. To optimize the parameters required for recovery of tin from waste
      PCBs, initially the bench scale studies were carried out using fresh solder
      (containing 52.6% Sn and 47.3% Pb) varying the acid concentration, temperature,
      mixing time and pulp density. The experimental data indicate that 95.79% of tin
      was leached out from solder material using 5.5M HCl at fixed pulp density 50 g/L
      and temperature 90 degrees C in mixing time 165 min. Kinetic studies followed the
      chemical reaction controlled dense constant size cylindrical particles with
      activation energy of 117.68 kJ/mol. However, 97.79% of tin was found to be
      leached out from solder materials of liberated swelled epoxy resin using 4.5M HCl
      at 90 degrees C, mixing time 60 min and pulp density 50 g/L. From the leach
      liquor of solder materials of epoxy resin, the precipitate of sodium stannate as
      value added product was obtained at pH 1.9. The Pb from the leach residue was
      removed by using 0.1M nitric acid at 90 degrees C in mixing time 45 min and pulp
      density 10g/L. The metal free epoxy resin could be disposed-of safely/used as
      filling material without affecting the environment.

PMID- 22647504
TI  - How do chemotherapeutic agents damage the ovary?
AB  - BACKGROUND: Chemotherapy treatment in premenopausal women is associated with an
      increased risk of premature ovarian failure (POF) but the exact mechanism through
      which this occurs is uncertain. In this review we examine the current evidence
      for the direct action of chemotherapeutic agents on the ovary and discuss
      possible molecular pathways through which follicle loss may occur. METHODS: A
      systemic search of the databases, PubMed and Google Scholar, was made for all
      English language articles through to 2011 in each subject area discussed.
      RESULTS: POF results from the loss of primordial follicles but this is not
      necessarily a direct effect of the chemotherapeutic agents. Instead, the
      disappearance of primordial follicles could be due to an increased rate of growth
      initiation to replace damaged developing follicles. Likewise, the loss of oocytes
      need not necessarily be a direct result of damage: evidence suggests that
      chemotherapy drugs can also induce oocyte death indirectly via damage to somatic
      cells. Specific molecular mechanisms and likely ovarian targets are discussed for
      some of the anti-cancer drugs most commonly used to treat premenopausal women.
      Finally, we consider current and prospective methods of preserving fertility.
      CONCLUSIONS: It is likely that different chemotherapeutic drugs act through a
      range of mechanisms and on different target cells. More research into the
      cellular mechanisms underpinning chemotherapy-induced follicle loss could lead to
      the generation of treatments specifically designed to prevent POF.

PMID- 22647505
TI  - Impact of fertility transmission and other sociodemographic factors on
      reproductive success and coalescent trees.
AB  - Summary Fertility transmission (FT) is a phenomenon with a cultural and/or
      genetic basis, whereby a positive correlation exists between the number of
      offspring of an individual and that of his/her parents. Theoretical studies using
      a haploid individual-based model have shown that FT increases the variance and
      intergenerational correlation in reproductive success and results in an imbalance
      in the coalescent tree of sampled genes. This phenomenon has been documented in
      several demographic studies conducted on the correlation in fertility between
      generations, or through the reconstruction of the genealogical trees of
      mitochondrial DNA sequences. However, as mtDNA is a single locus, potentially
      subject to other forces (e.g. natural selection), it is of interest to extend the
      theory of FT to nuclear loci. We show that because random mating between
      individuals leads to a mixing of their fertility profiles, FT in these cases will
      have less influence on the variance and intergenerational correlation of
      reproductive success. This, in turn, results in less impact on the shape of the
      coalescent trees. Nevertheless, in the presence of FT, high heterogeneity in
      reproductive success and homogamy for family size will increase the imbalance in
      the coalescent tree. Thus, FT should be easier to detect when occurring in
      conjunction with these other factors. We also show the utility of analysing
      different kinds of loci (X-linked, Y-linked, mitochondrial and autosomal) to
      assess whether FT is matrilineal, patrilineal or biparental. Finally, we
      demonstrate that the shape of the coalescent tree depends upon population size,
      in contrast to the classical Kingman's model.

PMID- 22647506
TI  - A key role of toll-like receptor 3 in tissue factor activation through
      extracellular signal regulated kinase 1/2 pathway in a murine hypoxia model.
AB  - Hypoxemia in the circulation can lead to venous thrombosis (VT) through tissue
      factor (TF) activation, but the mechanism of TF activation in hypoxia remains
      obscure. Ligands released from damaged tissues or cells due to hypoxia are
      identified by various pattern-recognition receptors (PRR), including Toll-like
      receptor3 (TLR3). In the present study, we investigated the mechanism of TF
      activation during acute hypoxia in a rat model. The expression of TLR3 and TF was
      analyzed by immunoblotting and RT-PCR. The TF activity was evaluated by two-stage
      chromogenic assay and fibrin deposition was detected by immunohistochemistry. The
      expression of TLR3, TF, and TF activity was increased significantly 6 h post
      acute hypoxia and then decreased gradually. The contribution of TLR3 in TF
      activation was investigated by poly I:C and TLR3 neutralizing antibody. We also
      found increased ERK phosphorylation both in acute hypoxia and poly I:C treatment.
      We further showed that the pre-treatment of TLR3 neutralizing antibody or ERK
      inhibitor (PD98059) 2 h prior to acute hypoxia or poly I:C treatment completely
      abrogated ERK phosphorylation and TF activation. The pre-treatment of TLR3
      neutralizing antibody also inhibited fibrin deposition in lung vasculature. These
      data indicate that acute hypoxia induced TF activation is mediated through TLR3
      ERK1/2 pathway.

PMID- 22647507
TI  - Dynamics of radiation exposure to marine biota in the area of the Fukushima NPP
      in March-May 2011.
AB  - Estimates of radiation dose rates are presented for marine biota in March-May
      2011 in the coastal zone near Fukushima NPP, and in the open sea. Calculations of
      fish contamination were made using two methods: a concentration factor approach,
      and a dynamic model. For representative marine organisms (fish and molluscs) the
      radiation dose rates did not exceed the reference level of 10 mGy/day. At a
      distance 30 km from the NPP, in the open sea the radiation doses for marine biota
      were much lower than those in the coastal zone near the NPP. Comparative
      estimates are presented for radiation doses to aquatic organisms in the exclusion
      zones of the Eastern Urals Radioactive Trail, and the Chernobyl NPP.

PMID- 22647508
TI  - [Topics for antiangiogenic therapy for glioblastoma].

PMID- 22647509
TI  - [Multidisciplinary treatment of leptomeningeal metastasis in patients with lung
      adenocarcinoma: the triple modality combination of EGFR-TKI, VP shunt and
      irradiation].
AB  - BACKGROUND: Leptomeningeal metastasis (LM) is a devastating complication of
      systemic cancers. New therapies that have beneficial effects on primary cancers
      outside the central nervous system (CNS) have underscored the significance of LM.
      Intrathecal chemotherapy plus radiation therapy are less effective for LM from
      lung adenocarcinoma. We retrospectively studied outcomes of patients with LM from
      lung adenocarcinoma who underwent multidisciplinary treatments in our institute.
      METHODS: Four patients with LM from lung adenocarcinoma treated with EGFR-TKI, VP
      shunt and irradiation. Of those four, two presented with increased intracranial
      pressure, one with epilepsy, and the other with truncal ataxia. Treatment was
      indicated when LM was confirmed by MR images or cytology, and Karnofsky
      Performance Status scale was more than 40%, and life expectancy was more than
      three months if LM was controlled. EGFR mutation was not examined, because of the
      unsettled approval of Japanese public health insurance at the time of this study.
      The patients selected for treatment by EGFR-TKI were all Asian women who had
      never smoked. Treatment sequence was based on clinical symptoms depending on the
      individual situation. RESULT: The mean time from diagnosis of lung adenocarcinoma
      to LM onset was 28 (24 to 36) months. Mean survival time from LM diagnosis was 9
      months. All patients died of LM. No patients suffered from peritoneal
      carcinomatosis or infection after VP shunt. CONCLUSION: The triple modality
      combination of EGFR-TKI, VP shunt and radiation therapy may improve outcomes and
      symptoms of patients with LM from lung adenocarcinoma.

PMID- 22647510
TI  - [Laparoscopy-assisted ventriculoperitoneal and lumboperitoneal shunt surgery].
AB  - Recently, laparoscopy (also referred to as minimally invasive surgery) has been
      used during peritoneal catheter implantation in shunt placement for
      hydrocephalus; however, the procedure and devices for this technique have not yet
      been well established. We adopted umbilical and paraumbilical laparoscopy for
      peritoneal catheter insertion. In this paper, we describe the technique we used
      and its clinical results and benefits. Ten consecutive patients with
      hydrocephalus who underwent laparoscopic shunt surgery (6 cases of
      ventriculoperitoneal shunt and 4 of lumboperitoneal shunt) were enrolled for this
      study. The follow-up period ranged from 21 to 434 days (mean, 263 days). After a
      standard cranial/spinal procedure, an approximately 5-mm incision was made in the
      lateral side of the umbilicus, where the abdominal catheter was introduced
      subcutaneously. Thereafter, we inserted a laparoscope into the peritoneal cavity
      via a small incision beneath or just on the umbilicus. A shunt catheter was
      laparoscopically inserted through a peel-off cannula and placed after taking note
      of the outflow of cerebrospinal fluid (CSF) from the catheter tip. In all
      patients, the shunt was inserted with no complications, and good patency was
      achieved. Laparoscopy allows implantation of the catheter into the peritoneal
      cavity, and the outflow of CSF can be confirmed intraoperatively. Furthermore,
      the abdominal surgical wounds are minimal, even for obese patients, and
      fascia/muscle incisions are not needed. Laparoscopy-assisted shunt surgery for
      hydrocephalus is effective and safe and also has cosmetic advantages.

PMID- 22647512
TI  - [Syringosubarachnoid shunt for noncommunicating syringomyelia associated with
      spinal lipoma: a case report].
AB  - Noncommunicating syringomyelia may complicate repeated untethering procedures in
      patients with spinal lipomas. Surgical intervention is indicated when
      syringomyelia is symptomatic. However, the preferred surgical procedure for
      noncommunicating syringomyelia associated with spinal lipomas has not been
      established. The authors report a case of noncommunicating syringomyelia
      associated with a spinal lipoma which was successfully treated with a
      syringosubarachnoid (S-S) shunt. The patient was a 9-year-old girl with a past
      history of an excision of a dermal sinus at the age of three months and an
      untethering of the spinal cord at the age of five. She developed a gait
      disturbance in the year prior to surgery, and a magnetic resonance imaging (MRI)
      study demonstrated syringomyelia from the second thoracic vertebra to the fourth
      lumbar vertebra. S-S shunt surgery successfully addressed the syringomyelia
      without adverse events, and a follow-up MRI study showed reduction of the size of
      the lesion. S-S shunt placement was therefore considered to be an effective
      treatment option for noncommunicating syringomyelia associated with a spinal
      lipoma.

PMID- 22647511
TI  - [A case of vein of Galen aneurysmal malformation with a newly developed dural
      arteriovenous fistula after successful embolization].
AB  - We report a case of vein of Galen aneurysmal malformation (VGAM) with a newly
      developed dural arteriovenous fistula (AVF) subsequent to successful
      embolization. A male neonate diagnosed as VGAM with prenatal ultrasonography and
      MRI presented severe cardiac and respiratory failure soon after birth. Five
      sessions of transarterial embolization using NBCA were performed during the first
      6 months of his life. The shunt flow was effectively reduced and heart failure
      was resolved after the treatment. Follow-up angiography performed 2.5 years after
      the last embolization revealed complete obliteration of VGAM and newly developed
      small dural AVF on the wall of the thrombosed falcorial sinus. We believe that
      the dural AVF in this case was caused by local venous hypertension or induction
      of angiogenic factor during the thrombosing process of VGAM.

PMID- 22647513
TI  - [A case of combined glossopharyngeal and trigeminal neuralgia].
AB  - It is well-known that idiopathic neuralgias of the trigeminal and
      glossopharyngeal nerves are caused by vascular compression at the root entry zone
      of the cranial nerves. Because they are functional diseases, initial treatment is
      medical, especially with carbamazepine. However, if medical therapy fails to
      adequately manage the pain, microvascular decompression (MVD) is prescribed.
      Glossopharyngeal neuralgia is rare, and combined trigeminal and glossopharyngeal
      neuralgia is an extremely rare disorder. A 70-year-old woman presented herself to
      Hokkaido Neurosurgical Memorial Hospital because of paroxysms of lancinating pain
      in her left pharynx and another lancinating pain in her left cheek.
      Carbamazepine, which was prescribed at another hospital, favorably relieved the
      pain; however, drug eruption compelled her to discontinue the medication. The
      multi-volume method revealed that a root entry zone of the left glossopharyngeal
      nerve was compressed by the left posterior inferior cerebellar artery, and the
      left trigeminal artery was compressed by the left superior cerebellar artery. MVD
      for both nerves was performed employing a left lateral suboccipital craniotomy.
      She experienced complete relief of pain immediately after MVD.  Combined
      trigeminal and glossopharyngeal neuralgia is extremely rare, but some groups
      noted a relatively high incidence of concurrent trigeminal neuralgia in patients
      with glossopharyngeal neuralgia up until the 1970's. Glossopharyngeal neuralgia
      includes pain near the gonion; therefore, there is an overlap of symptoms between
      glossopharyngeal and trigeminal neuralgias. By virtue of recent progress in
      imaging technology, minute preoperative evaluations of microvascular compression
      are possible. Until the 1970's, there might have been some misunderstanding
      regarding the overlap of symptoms because of lack of the concept of microvascular
      compression as a cause of neuralgia and rudimentary imaging technology. Minute
      evaluations of both symptoms and imaging are very important.

PMID- 22647514
TI  - [Intracardiac migration of a ventriculoatrial shunt catheter treated by
      endovascular transvenous retrieval].
AB  - The authors report a case of intracardiac migration of a ventriculoatrial (VA)
      shunt catheter and transvenous retrieval of the migrated shunt catheter. A 67
      year-old male, who had previously undergone a VA shunt for hydrocephalus after
      subarachnoid hemorrhage, presented disorientation, memory disturbance and gait
      disturbance without any cardiopulmonary symptom. Head CT scan revealed
      ventriculomegaly that indicated hydrocephalus due to shunt malfunction. Radiogram
      revealed that the caudal segment of the broken atrial catheter had migrated into
      the heart (right ventricle). The migrated shunt catheter was retrieved by a
      transfemoral approach with a pigtail catheter and a snare retriever catheter,
      although the rostral catheter segment partially remained because of tight
      adhesion. The VA shunt was then reconstructed. Postoperatively, symptoms due to
      recurrent hydrocephalus were markedly improved and the VA shunt functioned well.
      Transvenous catheter retrieval was a less invasive and effective method for VA
      shunt catheter migration.

PMID- 22647516
TI  - [Surgery for unruptured anterior cerebral artery aneurysms].
AB  - In Japan, a large number of surgical treatments for unruptured intracranial
      aneurysms have been performed. On the other hands, it is known that surgical
      treatment for unruptured intracranial aneurysms is the most frequent source of
      lawsuits in the neurosurgical field. Neurosurgeons have the duty to disclose all
      risks and consequences of a proposed surgical procedure to each patient.
      Moreover, precise knowledge of surgical risks would be helpful in preventing
      complications from occurring. However, it is almost impossible that a single
      surgeon or an institute have experiences with all possible surgical complications
      because there is limitation of the number of surgery. In this review series, we
      attempted an exhaustive bibliographic survey of the possible surgical
      complications including exceptional ones, and then, determined the frequency of
      each complications as far as possible quantitatively. In this paper, we focused
      on the complications of surgical treatment for anterior cerebral artery
      aneurysms.

PMID- 22647517
TI  - Effects of phlebotomy-induced reduction of body iron stores on metabolic
      syndrome: results from a randomized clinical trial.
AB  - BACKGROUND: Metabolic syndrome (METS) is an increasingly prevalent but poorly
      understood clinical condition characterized by insulin resistance, glucose
      intolerance, dyslipidemia, hypertension, and obesity. Increased oxidative stress
      catalyzed by accumulation of iron in excess of physiologic requirements has been
      implicated in the pathogenesis of METS, but the relationships between cause and
      effect remain uncertain. We tested the hypothesis that phlebotomy-induced
      reduction of body iron stores would alter the clinical presentation of METS,
      using a randomized trial. METHODS: In a randomized, controlled, single-blind
      clinical trial, 64 patients with METS were randomly assigned to iron reduction by
      phlebotomy (n = 33) or to a control group (n = 31), which was offered phlebotomy
      at the end of the study (waiting-list design). The iron-reduction patients had
      300 ml of blood removed at entry and between 250 and 500 ml removed after 4
      weeks, depending on ferritin levels at study entry. Primary outcomes were change
      in systolic blood pressure (SBP) and insulin sensitivity as measured by
      Homeostatic Model Assessment (HOMA) index after 6 weeks. Secondary outcomes
      included HbA1c, plasma glucose, blood lipids, and heart rate (HR). RESULTS: SBP
      decreased from 148.5 +/- 12.3 mmHg to 130.5 +/- 11.8 mmHg in the phlebotomy
      group, and from 144.7 +/- 14.4 mmHg to 143.8 +/- 11.9 mmHg in the control group
      (difference -16.6 mmHg; 95% CI -20.7 to -12.5; P < 0.001). No significant effect
      on HOMA index was seen. With regard to secondary outcomes, blood glucose, HbA1c,
      low-density lipoprotein/high-density lipoprotein ratio, and HR were significantly
      decreased by phlebotomy. Changes in BP and HOMA index correlated with ferritin
      reduction. CONCLUSIONS: In patients with METS, phlebotomy, with consecutive
      reduction of body iron stores, lowered BP and resulted in improvements in markers
      of cardiovascular risk and glycemic control. Blood donation may have beneficial
      effects for blood donors with METS. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01328210 Please see related article: http://www.biomedcentral.com/1741
      7015/10/53.

PMID- 22647518
TI  - A randomized, double-blind, active-controlled phase 2 trial to evaluate a novel
      selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus
      clopidogrel in patients undergoing nonurgent percutaneous coronary intervention:
      the INNOVATE-PCI trial.
AB  - BACKGROUND: We evaluated the safety, efficacy, and tolerability of elinogrel, a
      competitive, reversible intravenous and oral P2Y(12) inhibitor that does not
      require metabolic activation, in patients undergoing nonurgent percutaneous
      coronary intervention. METHODS AND RESULTS: In a randomized, double-blind, dose
      ranging phase 2b trial, 652 patients received either 300 or 600 mg of clopidogrel
      pre-percutaneous coronary intervention followed by 75 mg daily or 80 or 120 mg of
      IV elinogrel followed by 50, 100, or 150 mg oral elinogrel twice daily. Numerous
      exploratory safety and efficacy end points were assessed and, as such, had no
      prespecified primary end point, and the study was not powered to conclusively
      evaluate its objectives. Thrombolysis in myocardial infarction combined bleeding
      was increased with elinogrel (hazard ratio, 1.98; 95% confidence interval, 1.10
      to 3.57), related largely to increased bleeding requiring medical attention
      (elinogrel 47/408 [11.5%] versus clopidogrel 13/208 [6.3%]) and occurring
      primarily at the percutaneous coronary intervention access site. Efficacy end
      points and postprocedure cardiac enzyme were similar, but there was a
      nonsignificant higher frequency of periprocedural myocardial infarctions in the
      elinogrel arms (OR, 1.59; 95% confidence interval, 0.79 to 3.48). There was an
      increased incidence of dyspnea (elinogrel 50/408 [12.3%] versus clopidogrel 8/208
      [3.8%]) and transaminase elevation (alanine transferase/aspartate transferase >3*
      the upper limit of normal; elinogrel 18/408 [4.4%] versus clopidogrel 2/208
      [1.0%]) in the elinogrel arms, but there were no cases of heart block,
      bradycardia, hypotension, or liver failure. CONCLUSIONS: In patients undergoing
      nonurgent percutaneous coronary intervention and in comparison with clopidogrel,
      intravenous and oral elinogrel therapy did not significantly increase
      thrombolysis in myocardial infarction major or minor bleeding, although bleeding
      requiring medical attention was more common. The significance of these findings
      will need to be more definitively determined in future Phase 3 studies. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00751231.

PMID- 22647519
TI  - Comparison of hyperemic efficacy between central and peripheral venous adenosine
      infusion for fractional flow reserve measurement.
AB  - BACKGROUND: Maximal hyperemia is a prerequisite for the accurate measurement of
      fractional flow reserve (FFR). Although continuous infusion of adenosine via the
      femoral vein is considered to be the gold standard, this requires an additional
      invasive procedure for femoral vein access and is difficult to use during
      transradial coronary catheterization. We performed this prospective study to
      evaluate the feasibility and efficacy of peripheral intravenous infusion of
      adenosine for FFR measurement. METHODS AND RESULTS: Seventy-one patients were
      prospectively enrolled, and FFR was measured using a 0.014-inch coronary pressure
      wire. Hyperemic efficacy of adenosine was compared among intracoronary bolus
      injection and continuous IV infusion (140 MUg/min/kg) via the femoral and via the
      forearm vein. In 20 patients, hyperemic mean transit time and index of
      microcirculatory resistance were also measured. Mean FFR after bolus
      administration of adenosine was 0.81+/-0.10. As compared with femoral vein
      infusion (FFR: 0.80+/-0.10), hyperemic efficacy of forearm vein infusion of
      adenosine (FFR: 0.80+/-0.11) was not inferior (P for noninferiority=0.01). The
      number of functionally significant stenoses (FFR <0.75) was also not different
      between the 2 methods (femoral vein versus forearm vein; 17 (25.0%) versus 17
      (25.0%), P=1.0). Both hyperemic mean transit time and index of microcirculatory
      resistance were not different between the 2 routes of adenosine infusion.
      Additional bolus injection of adenosine during IV infusion did not improve the
      hyperemic efficacy but increased the risk of atrioventricular block. CONCLUSIONS:
      This study suggests that continuous intravenous infusion of adenosine via the
      forearm vein is a convenient and effective way to induce steady-state hyperemia
      for invasive physiological measurements. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01070420.

PMID- 22647520
TI  - Comparison of invasive and noninvasive assessment of aortic stenosis severity in
      the elderly.
AB  - BACKGROUND: Aortic valve area (AVA) in aortic stenosis (AS) can be assessed
      noninvasively or invasively, typically with similar results. These techniques
      have not been validated in elderly patients, where common assumptions make them
      most prone to error. Accurate assessment of AVA is crucial to determine which
      patients are appropriate candidates for aortic valve replacement. METHODS AND
      RESULTS: Fifty elderly patients (mean 86 years, 46% female) referred for cardiac
      catheterization to evaluate AS also underwent transthoracic echocardiography
      within 24 hours. To minimize assumptions all patients had 3-dimensional
      echocardiography (Echo-3D), and at catheterization using directly measured oxygen
      consumption (Cath-mVo(2)) and thermodilution cardiac output (Cath-TD).
      Correlation between Cath-mVo(2) and Echo-3D AVA was poor (r=0.41). Cath-TD AVA
      had a moderate correlation with Echo-3D AVA (r=0.59). Cath-mVo(2) (AVA=0.69
      cm(2)) and Cath-TD (AVA=0.66 cm(2)) underestimated AVA compared with Echo-3D
      (AVA=0.76 cm(2;) P=0.08 for comparison with Cath-mVo(2); P=0.001 for Cath-TD).
      Compared with Echo-3D, the sensitivity and specificity for determining critical
      disease (AVA <0.8 cm(2)) were 81% and 42% for Cath-mVo(2), and 97% and 53% for
      Cath-TD. The only independent predictor of the difference between noninvasive and
      invasive AVA was stroke volume index (P<0.01). Resistance, a less flow-dependent
      measure, showed a stronger correlation between Echo-3D and Cath-mVo(2) (r=0.69),
      and Echo-3D and Cath-TD (r=0.77). CONCLUSIONS: Standard techniques of AVA
      assessment for AS show poor correlation in elderly patients, with frequent
      misclassification of critical AS. Less flow-dependent measures, such as
      resistance, should be considered to ensure that only appropriate patients are
      treated with aortic valve replacement.

PMID- 22647521
TI  - Oxytocin enhances resting-state connectivity between amygdala and medial frontal
      cortex.
AB  - The neuropeptide oxytocin (OXT) plays an important role in complex socio
      affective behaviours such as affiliation, attachment, stress and anxiety.
      Previous studies have focused on the amygdala as an important target of OXT's
      effects. However, the effects of OXT on connectivity of the amygdala with
      cortical regions such as medial frontal cortex, an important mediator of social
      cognition and emotion regulation, remain unexplored. In a randomized, double
      blind, cross-over design, 15 volunteers received intranasal OXT or placebo prior
      to resting-state functional magnetic resonance imaging. OXT significantly
      increased connectivity between both amygdalae and rostral medial frontal cortex
      (rmFC), while having only negligible effects on coupling with other brain
      regions. These results demonstrate that OXT is a robust and highly selective
      enhancer of amygdala connectivity with rmFC, a region critical to social
      cognition and emotion regulation, and add to our understanding of the neural
      mechanisms by which OXT modulates complex social and cognitive behaviours.

PMID- 22647522
TI  - Elevated interleukin-18 serum levels in chronic schizophrenia: Association with
      psychopathology.
AB  - BACKGROUND: Schizophrenia is associated with various abnormalities in the immune
      system including elevated levels of Interleukin-18 (IL-18), a potent inflammatory
      cytokine in T-helper 1 (Th1) responses. The aim of this study was to assess the
      clinical significance of serum IL-18 levels in various stages of schizophrenia.
      METHODS: We measured serum IL-18 levels using a sandwich enzyme-linked
      immunosorbent assay (ELISA) from 78 never-medicated first-episode schizophrenia,
      79 medicated chronic schizophrenia and 78 healthy control subjects. The symptoms
      of schizophrenia were assessed by the Positive and Negative Syndrome Scale
      (PANSS). RESULTS: The chronic patients had significantly greater serum IL-18
      levels than both first-episode patients and controls. Serum IL-18 was also
      positively correlated with the PANSS general psychopathology subscore in chronic
      schizophrenic patients. CONCLUSIONS: Our results showed elevated IL-18 pathway
      activity may be involved in the psychopathology of schizophrenia.

PMID- 22647523
TI  - 'Impulsive compulsivity' in obsessive-compulsive disorder: a phenotypic marker of
      patients with poor clinical outcome.
AB  - Although traditionally obsessive-compulsive disorder (OCD) and impulse control
      disorders (ICD) have represented opposing ends of a continuum, recent research
      has demonstrated a frequent co-occurrence of impulsive and compulsive behaviours,
      which may contribute to a worse clinical picture of some psychiatric disorders.
      We hypothesize that individuals with 'impulsive' OCD as characterized by poor
      insight, low resistance, and reduced control towards their compulsions will have
      a deteriorative course, greater severity of hoarding and/or symmetry/ordering
      symptoms, and comorbid ICD and/or substance use disorders (SUD). The sample
      consisted of 869 individuals with a minimum score of 16 on the Yale-Brown
      Obsessive Compulsive Scale (Y-BOCS). Of these, 65 had poor insight, low
      resistance, and reduced control towards compulsions ('poor IRC') and 444 had
      preserved insight, greater resistance and better control over compulsions ('good
      IRC'). These two groups were compared on a number of clinical and demographic
      variables. Individuals with poor IRC were significantly more likely to have a
      deteriorative course (p < 0.001), longer duration of obsessions (p = 0.017),
      greater severity of symmetry/ordering (p < 0.001), contamination/cleaning (p <
      0.001) and hoarding (p = 0.002) symptoms, and comorbid intermittent explosive
      disorder (p = 0.026), trichotillomania (p = 0.014) and compulsive buying (p =
      0.040). Regression analysis revealed that duration of obsessions (p = 0.037) and
      hoarding severity (p = 0.005) were significant predictors of poor IRC. In the
      absence of specific measures for impulsivity in OCD, the study highlights the
      utility of simple measures such as insight, resistance and control over
      compulsions as a phenotypic marker of a subgroup of OCD with impulsive features
      demonstrating poor clinical outcome.

PMID- 22647524
TI  - ANK3 and CACNA1C--missing genetic link for bipolar disorder and major depressive
      disorder in two German case-control samples.
AB  - Recent genome-wide association studies (GWAS) and metaanalyses revealed genetic
      associations for ANK3 (ankyrin 3) and CACNA1C (alpha 1C subunit of the L-type
      voltage gated calcium channel) with bipolar disorder (BPD). Several findings from
      clinical, epidemiological, and genetic studies point towards a common biological
      background of BPD and major depressive disorder (MDD). We were interested whether
      this also applies for ANK3 and CACNA1C and tested associations of single
      nucleotide polymorphisms (SNPs) in these genes with MDD in two Caucasian case
      control samples. Sample 1 (Munich Antidepressant Response Signature Project/MARS 
      MDD) consisted of 720 depressed inpatients and 542 psychiatric healthy controls.
      Sample 2 (unipolar recurrent depression (URD)) consisted of 827 patients with URD
      and 860 psychiatric healthy controls. After stringent quality control we analyzed
      262 SNPs (sample 1) and 504 SNPs (sample 2) and imputed further 5771 SNPs (sample
      1) and 5534 SNPs (sample 2) from Hapmap Phase 2 data in the ANK3 and CACNA1C gene
      regions. Additionally, a metaanalysis of both samples was performed. Several SNPs
      in both genes were nominally associated with MDD with the highest association in
      the 3'-region of ANK3 (rs10994143, nominal p = 3.3*10(-4)) in the metaanalysis of
      both samples. None of these results remained significant after correction for
      multiple testing. No association of MDD with SNPs previously reported in BPD
      studies could be detected. By analyzing the LD-structure, our highest associated
      SNPs could not be linked to the SNPs previously reported in BPD. Regarding ANK3
      and CACNA1C, our findings do not support a strong genetic link between BPD and
      MDD for these two genes.

PMID- 22647525
TI  - A gene-protein assay for human epidermal growth factor receptor 2 (HER2):
      brightfield tricolor visualization of HER2 protein, the HER2 gene, and chromosome
      17 centromere (CEN17) in formalin-fixed, paraffin-embedded breast cancer tissue
      sections.
AB  - BACKGROUND: The eligibility of breast cancer patients for human epidermal growth
      factor receptor 2 (HER2)-directed therapies is determined by the HER2 gene
      amplification and/or HER2 protein overexpression status of the breast tumor as
      determined by in situ hybridization (ISH) or immunohistochemistry (IHC),
      respectively. Our objective was to combine the US Food and Drug Administration
      (FDA)-approved HER2 & chromosome 17 centromere (CEN17) brightfield ISH (BISH) and
      HER2 IHC assays into a single automated HER2 gene-protein assay allowing
      simultaneous detection of all three targets in a single tissue section. METHODS:
      The HER2 gene-protein assay was optimized using formalin-fixed, paraffin-embedded
      (FFPE) samples of the xenograft tumors MCF7 [HER2 negative (non-amplified gene,
      protein negative)] and Calu-3 [HER2 positive (amplified gene, protein positive)].
      HER2 IHC was performed using a rabbit monoclonal anti-HER2 antibody (clone 4B5)
      and a conventional 3,3'-diaminobenzidine IHC detection. The HER2 & CEN17 BISH
      signals were visualized using horseradish peroxidase-based silver and alkaline
      phosphatase-based red detection systems, respectively with a cocktail of 2,4
      dinitrophenyl-labeled HER2 and digoxigenin-labeled CEN17 probes. The performance
      of the gene-protein assay on tissue microarray slides containing 189 randomly
      selected FFPE clinical breast cancer tissue cores was compared to that of the
      separate HER2 IHC and HER2 & CEN17 BISH assays. RESULTS: HER2 protein detection
      was optimal when the HER2 IHC protocol was used before (rather than after) the
      BISH protocol. The sequential use of HER2 IHC and HER2 & CEN17 BISH detection
      steps on FFPE xenograft tumor sections appropriately co-localized the HER2
      protein, HER2 gene, and CEN17 signals after mitigating the silver background
      staining by using a naphthol phosphate-containing hybridization buffer for the
      hybridization step. The HER2 protein and HER2 gene status obtained using the
      multiplex HER2 gene-protein assay demonstrated high concordance with those
      obtained using the separate HER2 IHC and HER2 & CEN17 BISH assays, respectively.
      CONCLUSIONS: We have developed a protocol that allows simultaneous visualization
      of the HER2 IHC and HER2 & CEN17 BISH targets. This automated protocol
      facilitated the determination of HER2 protein and HER2 gene status in randomly
      selected breast cancer samples, particularly in cases that were equivocal or
      exhibited tumor heterogeneity. The HER2 gene-protein assay produced results
      virtually equivalent to those of the single FDA-approved HER2 IHC and HER2 &
      CEN17 BISH assays. VIRTUAL SLIDES: The virtual slides for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/2041964038705297.

PMID- 22647526
TI  - Mechanisms for differentiation between cognate and near-cognate ligands by purine
      riboswitches.
AB  - Riboswitches are elements in the 5'-untranslated region of mRNAs that regulate
      gene expression by directly interacting with metabolites related to their own
      gene products. A remarkable feature of this gene regulation mechanism is the high
      specificity of riboswitches for their cognate ligands. In this study, we used a
      combination of static and time-resolved NMR-spectroscopic methods to investigate
      the mechanisms for ligand specificity in purine riboswitches. We investigate the
      xpt-aptamer domain from a guanine-responsive riboswitch and the mfl-aptamer
      domain from a 2'-deoxyguanosine-responsive riboswitch. The xpt-aptamer binds the
      purine nucleobases guanine/hypoxanthine with high affinity, but, unexpectedly,
      also the nucleoside 2'-deoxyguanosine. On the other hand, the mfl-aptamer is
      highly specific for its cognate ligand 2'-deoxyguanosine, and does not bind
      purine ligands. We addressed the question of aptamer's ligand specificity by real
      time NMR spectroscopy. Our studies of ligand binding and subsequently induced
      aptamer folding revealed that the xpt-aptamer discriminates against non-cognate
      ligands by enhanced life-times of the cognate complex compared with non-cognate
      complexes, whereas the mfl-aptamer rejects non-cognate ligands at the level of
      ligand association, employing a kinetic proofreading mechanism.

PMID- 22647527
TI  - Satellite DNA-associated siRNAs as mediators of heat shock response in insects.
AB  - Conversion of environmental signals into epigenetic information is thought to
      occur widely but has been poorly studied as yet. It is proposed that changes in
      the expression of molecules involved in chromatin modifications might play a role
      in this process. Here we study the expression of abundant satellite DNA TCAST
      that makes up 35% of genome of the red flour beetle Tribolium castaneum and is
      located within the constitutive pericentromeric heterochromatin. RNA polymerase
      II promotes the transcription of TCAST satellite DNA from both strands, and long
      primary transcripts are rapidly processed into 21-30 nt siRNAs. Expression of
      TCAST satellite DNA-associated siRNAs is developmentally regulated, the most
      intense being at specific stages of embryogenesis. Moreover, the expression is
      strongly induced following heat shock and is accompanied by increase in
      repressive epigenetic modifications of histones at TCAST regions. Upon recovery
      from heat stress, the expression of satellite DNA-associated siRNAs as well as
      histone modifications is quickly restored. Our results indicate that satellite
      DNA-associated siRNAs, transiently activated after heat shock, affect epigenetic
      state of constitutive heterochromatin in Tribolium. It can be hypothesized that
      transient remodeling of heterochromatin is part of a physiological gene
      expression program activated under stress conditions in insects.

PMID- 22647529
TI  - RNA polymerase V-dependent small RNAs in Arabidopsis originate from small,
      intergenic loci including most SINE repeats.
AB  - In plants, heterochromatin is maintained by a small RNA-based gene silencing
      mechanism known as RNA-directed DNA methylation (RdDM). RdDM requires the non
      redundant functions of two plant-specific DNA-dependent RNA polymerases (RNAP),
      RNAP IV and RNAP V. RNAP IV plays a major role in siRNA biogenesis, while RNAP V
      may recruit DNA methylation machinery to target endogenous loci for silencing.
      Although small RNA-generating regions that are dependent on both RNAP IV and RNAP
      V have been identified previously, the genomic loci targeted by RNAP V for siRNA
      accumulation and silencing have not been described extensively. To characterize
      the RNAP V-dependent, heterochromatic siRNA-generating regions in the Arabidopsis
      genome, we deeply sequenced the small RNA populations of wild-type and RNAP V
      null mutant (nrpe1) plants. Our results showed that RNAP V-dependent siRNA
      generating loci are associated predominately with short repetitive sequences in
      intergenic regions. Suppression of small RNA production from short repetitive
      sequences was also prominent in RdDM mutants including dms4, drd1, dms3 and rdm1,
      reflecting the known association of these RdDM effectors with RNAP V. The genomic
      regions targeted by RNAP V were small, with an estimated average length of 238
      bp. Our results suggest that RNAP V affects siRNA production from genomic loci
      with features dissimilar to known RNAP IV-dependent loci. RNAP V, along with RNAP
      IV and DRM1/2, may target and silence a set of small, intergenic transposable
      elements located in dispersed genomic regions for silencing. Silencing at these
      loci may be actively reinforced by RdDM.

PMID- 22647530
TI  - Efficacy of an imidacloprid/flumethrin collar against fleas, ticks, mites and
      lice on dogs.
AB  - BACKGROUND: The studies reported here were conducted to ascertain the efficacy of
      imidacloprid/flumethrin incorporated in a slow-release matrix collar, against
      infestations of dogs by fleas, ticks, mites and lice. Efficacy was evaluated
      against the flea Ctenocephalides felis felis, the ticks Rhipicephalus sanguineus,
      Ixodes ricinus, Ixodes scapularis, Dermacentor reticulatus and Dermacentor
      variabilis, the mite Sarcoptes scabiei and the biting louse Trichodectes canis.
      METHODS: Groups of collar-treated dogs (n = 7-10) were infested with fleas and/or
      ticks at monthly intervals at least, over a period of up to 8 months. Efficacy
      against fleas was evaluated 24 to 48 h after treatment and 24 h after each re
      infestation. Efficacy against ticks was evaluated at 48 h (acaricidal), 6 h
      (repellent) and 48 h (sustained) after infestation. The effect of regular
      shampooing or immersion in water on the efficacy of the collars was also tested.
      Efficacy against flea larvae was assessed by incubating blanket samples after dog
      contact with viable flea eggs. Effectiveness against lice and mites was evaluated
      after treatment of naturally infested animals. With the exception of the mites,
      efficacy was calculated by comparison with untreated negative control groups.
      RESULTS: Efficacy against fleas (24 h) generally exceeded 95%, and against flea
      larvae it exceeded 99% for 8 months. Sustained acaricidal (48 h) efficacy,
      covering a period of 8 months was 100% against I. ricinus, starting 2 days after
      treatment (in vivo), and 100% against I. scapularis (in vitro), above 97% against
      R. sanguineus, generally above 97% against D. reticulatus and above 90% for D.
      variabilis.Repellent (6 h) efficacy 2 days after treatment and continuing for 8
      months was consistently 100% against I. ricinus, and above 90% against R.
      sanguineus.Regular shampooing affected efficacy against fleas and ticks to a
      lesser extent than regular immersion in water.The collars eliminated Trichodectes
      canis within 2 days and Sarcoptes scabiei within 3 months. CONCLUSION: The rapid
      insecticidal and acaricidal properties of the medicated collars against newly
      acquired infestations of fleas and ticks and their sustained high levels of
      preventive efficacy have been clearly shown. Consequently they have the potential
      to prevent the transmission of vector-borne diseases and other conditions
      directly associated with infestation throughout an entire season of parasite
      abundance.

PMID- 22647531
TI  - Chitosan encapsulated quantum dots platform for leukemia detection.
AB  - We report results of the studies relating to electrophoretic deposition of
      nanostructured composite of chitosan (CS)-cadmium-telluride quantum dots (CdTe
      QDs) onto indium-tin-oxide coated glass substrate. The high resolution
      transmission electron microscopic studies of the nanocomposite reveal molecular
      level coating of the CdTe-QDs with CS molecules in the colloidal dispersion
      medium. This novel composite platform has been explored to fabricate an
      electrochemical DNA biosensor for detection of chronic myelogenous leukemia (CML)
      by immobilizing amine terminated oligonucleotide probe sequence containing 22
      base pairs, identified from BCR-ABL fusion gene. The results of differential
      pulse voltammetry reveal that this nucleic acid sensor can detect as low as 2.56
      pM concentration of complementary target DNA with a response time of 60s.
      Further, the response characteristics show that this fabricated bioelectrode has
      a shelf life of about 6 weeks and can be used for about 5-6 times. The results of
      experiments conducted using clinical patient samples reveal that this sensor can
      be used to distinguish CML positive and the negative control samples.

PMID- 22647532
TI  - Rapid detection of avian influenza H5N1 virus using impedance measurement of
      immuno-reaction coupled with RBC amplification.
AB  - Avian influenza virus (AIV) subtype H5N1 was first discovered in the 1990 s and
      since then its emergence has become a likely source of a global pandemic and
      economic loss. Currently accepted gold standard methods of influenza detection,
      viral culture and rRT-PCR, are time consuming, expensive and require special
      training and laboratory facilities. A rapid, sensitive, and specific screening
      method is needed for in-field or bedside testing of AI virus to effectively
      implement quarantines and medications. Therefore, the objective of this study was
      to improve the specificity and sensitivity of an impedance biosensor that has
      been developed for the screening of AIV H5. Three major components of the
      developed biosensor are immunomagnetic nanoparticles for the separation of AI
      virus, a microfluidic chip for sample control and an interdigitated
      microelectrode for impedance measurement. In this study polyclonal antibody
      against N1 subtype was immobilized on the surface of the microelectrode to
      specifically bind AIV H5N1 to generate more specific impedance signal and chicken
      red blood cells (RBC) were used as biolabels to attach to AIV H5N1 captured on
      the microelectrode to amplify impedance signal. RBC amplification was shown to
      increase the impedance signal change by more than 100% compared to the protocol
      without RBC biolabels, and was necessary for forming a linear calibration curve
      for the biosensor. The use of a second antibody against N1 offered much greater
      specificity and reliability than the previous biosensor protocol. The biosensor
      was able to detect AIV H5N1 at concentrations down to 10(3) EID(50)ml(-1) in less
      than 2h.

PMID- 22647533
TI  - CuO thin film based uric acid biosensor with enhanced response characteristics.
AB  - An efficient reagentless uric acid biosensor has been realized using a copper
      oxide (CuO) thin film matrix grown onto platinum (Pt) coated corning glass
      substrates by pulsed laser deposition (PLD) technique. The p-type CuO matrix
      successfully introduces redox property in the electrode and provides enhanced
      electron communication features. Sensing response obtained by the
      bioelectrocatalytic oxidation of uric acid by uricase/CuO/Pt/glass electrode was
      studied without any external mediator using cyclic voltammetry (CV) and
      photometric assay. The studies reveal that the uricase/CuO/Pt/glass bio-electrode
      exhibits good linearity over a wide range of 0.05 mM to 1.0mM uric acid
      concentration with enhanced response of 2.7 mA/mM and high shelf life (>14
      weeks). A low Michaelis-Menten constant (K(m)) of 0.12 mM, indicate that the
      immobilized enzyme (uricase) has enhanced affinity towards its analyte (uric
      acid). The results confirm promising application of the p-type CuO thin film
      matrix for the realization of a reagentless integrated implantable biosensor.

PMID- 22647534
TI  - A SERS-based immunoassay with highly increased sensitivity using gold/silver core
      shell nanorods.
AB  - An immunoassay based on surface enhanced Raman scattering (SERS) has been
      developed using immuno-gold/silver core-shell nanorods with a high sensitivity.
      The features of these nanoparticles were characterized by UV-vis extinction
      spectra, TEM images, EDX analyses and SERS spectra. It was found that the
      obtained gold/silver core-shell nanorods showed a much higher SERS activity than
      uncoated gold nanorods. After the gold/silver core-shell nanorods were modified
      with antibody and employed in immunoassay, the antigen concentration-dependent
      SERS spectra and dose-response calibration curves were obtained. By comparison,
      it can be concluded that the detection limit of gold/silver core-shell nanorods
      based immunoassay reaches 70 fM, which is 10(4) times lower than gold nanorods
      based detection. As a result, SERS probes fabricated with gold/silver core-shell
      nanorods are demonstrated to be advantageous to those synthesized with gold
      nanorods due to their highly increased sensitivity in sandwich immunoassay, which
      also indicates the potential use of these gold/silver core-shell nanorods in
      other biological sensing applications.

PMID- 22647535
TI  - Highly sensitive visible light activated photoelectrochemical biosensing of
      organophosphate pesticide using biofunctional crossed bismuth oxyiodide flake
      arrays.
AB  - A new, highly sensitive and selective biosensor for the photoelectrochemical
      (PEC) detection of organophosphate pesticides (OPs) has been developed, whereby
      newly synthesized crossed bismuth oxyiodide (BiOI) nanoflake arrays (BiOINFs) are
      fabricated as a photoactive electrode via a successive ionic layer adsorption and
      reaction (SILAR) approach. The smart integration of BiOINFs with biomolecules
      acetylcholinesterase (AChE) yields a novel AChE-BiOINFs hybrid, constructing a
      three-dimensional (3D) porous network biosensing platform. The composition and
      surface structure of the sensor were carefully characterized by X-ray diffraction
      (XRD), scanning electron microscopy (SEM), and various electrochemical
      techniques. Such interlaced network architectures, providing better mass
      transport and allowing more AChE loading per unit area, as well as the
      intrinsically strong visible light-harvesting effect from BiOI, greatly
      facilitate the PEC responses. On the basis of the effect of OPs on the
      photocurrent of AChE-BiOINFs/ITO, a highly sensitive visible light-activated
      photoelectrochemical biosensor was developed for biosensing OPs. The conditions
      for OPs detection were optimized by using methyl parathion (MP) as a model OP
      compound. Under the optimized experimental conditions, our results show that such
      a newly designed AChE-BiOINFs/ITO photoactive electrode provides remarkably
      improved sensitivity and selectivity for the biosensing of OPs. The detection
      limit was found to be as low as about 0.04 ng mL(-1) (S/N=3). Toward the goal for
      practical applications, the resulting sensor was further evaluated by monitoring
      MP in spiked vegetable samples, showing fine applicability for the detection of
      MP in real samples.

PMID- 22647536
TI  - Associations of current and remitted major depressive disorder with brain
      atrophy: the AGES-Reykjavik Study.
AB  - BACKGROUND: To examine whether lifetime DSM-IV diagnosis of major depressive
      disorder (MDD), including age at onset and number of episodes, is associated with
      brain atrophy in older persons without dementia. METHOD: Within the population
      based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 4354 persons
      (mean age 76 +/- 5 years, 58% women) without dementia had a 1.5-T brain magnetic
      resonance imaging (MRI) scan. Automated brain segmentation total and regional
      brain volumes were calculated. History of MDD, including age at onset and number
      of episodes, and MDD in the past 2 weeks was diagnosed according to DSM-IV
      criteria using the Mini-International Neuropsychiatric Interview (MINI). RESULTS:
      Of the total sample, 4.5% reported a lifetime history of MDD; 1.5% had a current
      diagnosis of MDD (including 75% with a prior history of depression) and 3.0% had
      a past but no current diagnosis (remission). After adjusting for multiple
      covariates, compared to participants never depressed, those with current MDD
      (irrespective of past) had more global brain atrophy [B = -1.25%, 95% confidence
      interval (CI) -2.05 to -0.44], including more gray- and white-matter atrophy in
      most lobes, and also more atrophy of the hippocampus and thalamus. Participants
      with current, first-onset MDD also had more brain atrophy (B = -1.62%, 95% CI 
      3.30 to 0.05) whereas those remitted did not (B = 0.06%, 95% CI -0.54 to 0.66).
      CONCLUSIONS: In older persons without dementia, current MDD, irrespective of
      prior history, but not remitted MDD was associated with widespread gray- and
      white-matter brain atrophy. Prospective studies should examine whether MDD is a
      consequence of, or contributes to, brain volume loss and development of dementia.

PMID- 22647537
TI  - Immunohistochemical detection of cytoplasmic LC3 puncta in human cancer
      specimens.
AB  - Autophagy is an evolutionarily conserved catabolic process that involves the
      entrapment of cytoplasmic components within characteristic vesicles for their
      delivery to and degradation within lysosomes. Alterations in autophagic signaling
      are found in several human diseases including cancer. Here, we describe a
      validated immunohistochemical protocol for the detection of LC3 puncta in human
      formalin-fixed, paraffin-embedded cancer specimens that can also be applied to
      mouse tissues. In response to systemic chemotherapy, autophagy-competent mouse
      tumors exhibited LC3 puncta, which did not appear in mouse cancers that had been
      rendered autophagy-deficient by the knockdown of Atg5 or Atg7. As compared with
      normal tissues, LC3 staining was moderately to highly elevated in the large
      majority of human cancers studied, albeit tumors of the same histological type
      tended to be highly heterogeneous in the number and intensity of LC3 puncta per
      cell. Moreover, tumor-infiltrating immune cells often were highly positive for
      LC3. Altogether, this protocol for LC3 staining appears suitable for the specific
      detection of LC3 puncta in human specimens, including tissue microarrays. We
      surmise that this technique can be employed for retrospective or prospective
      studies involving large series of human tumor samples.

PMID- 22647538
TI  - Specific elevation of DcR3 in sera of sepsis patients and its potential role as a
      clinically important biomarker of sepsis.
AB  - Because of its potentially important role in the pathogenesis of sepsis, the
      expression of soluble decoy receptor 3 (DcR3) was investigated in sera of sepsis
      patients. The serum levels of DcR3 and its tumor necrosis factor-like ligand TL1A
      and homologous decoy receptor OPG were quantified by ELISA. The values of DcR3 to
      diagnose sepsis were analyzed by receiver-operating characteristic (ROC) curves.
      The results showed that DcR3 was significantly elevated in sepsis compared to
      systemic inflammatory response syndrome (SIRS), a condition similar to sepsis but
      resulting from noninfectious insults. DcR3 showed superior area under the ROC
      curve (AUC, 0.958) compared to poor AUCs of TL1A and OPG. At a cut-off of 3.24
      ng/mL, DcR3 predicted sepsis from SIRS with 96% sensitivity and 82.6%
      specificity. DcR3 also predicted sepsis from cancer and inflammatory bowel
      disease with equally excellent values. Therefore, DcR3 serum level has the
      potential to serve as a reliable biomarker of sepsis.

PMID- 22647539
TI  - Clinical islet transplantation:  where immunity and metabolism intersect?
AB  - PURPOSE OF REVIEW: The dramatic results of the Edmonton Protocol in 2000
      triggered tremendous excitement over the application of pancreatic islet
      transplantation as a viable approach to achieving consistent insulin independence
      in type 1 diabetic patients. However, this optimism in the field was tempered by
      follow-up studies showing frequent attrition of graft function commonly requiring
      a return to exogenous insulin therapy within 1-3 years after transplant. The
      purpose of this review is to put these initial studies in perspective and to
      highlight progress and challenges in this important field. RECENT FINDINGS:
      Recent clinical and experimental findings demonstrate a progressive improvement
      in the function and durability of islet allografts. Induction therapies targeting
      T lymphocytes and costimulatory pathways have been highly effective at promoting
      islet transplant function. It is also apparent that islet injury associated with
      metabolic distress provides a nonimmune barrier to islet transplant outcomes.
      SUMMARY: Newer therapeutic interventions show great promise for attenuating the
      adaptive immune response to islet allografts. Also, clarifying the mechanisms of
      metabolic-related tissue distress may provide additional potential targets for
      improving islet graft outcomes.

PMID- 22647540
TI  - Urinary levoglucosan levels in Austrian communities differing in agrarian quota.
AB  - Levoglucosan is a sugar anhydride produced by combustion of carbohydrates. In
      ambient monitoring it serves as an indicator for wood smoke. Its use in human
      biomonitoring, however, is not yet widespread. This study investigated whether
      levoglucosan in urine is a suitable biomarker for regional differences in wood
      smoke exposure in the winter season. Within the first Austrian biomonitoring
      survey, pooled urine samples from mothers as well as children of five communities
      of different size (two-stage random stratified sampling) were analysed by HPLC.
      As an indicator of exposure to polycyclic aromatic hydrocarbons (PAH) that are
      also prevalent in wood smoke, 1-hydroxypyrene was determined. In each town
      levoglucosan was found in higher levels in the pooled children's samples than in
      the pooled mothers' samples. It correlated well with the agrarian quota. 1
      Hydroxypyrene concentrations were higher in areas with higher population density.
      Correlation of urinary levoglucosan concentrations with the agrarian quota may be
      explained by higher wood smoke exposure in communities with higher agrarian
      quota. To our knowledge this study is the first investigation on this issue in
      Europe. It indicates that human biomonitoring of levoglucosan may be suitable to
      detect differences in regional exposure to wood smoke.

PMID- 22647541
TI  - Long bone metastasis from squamous cell carcinoma of the base of the tongue.
AB  - We report a case of a 79-year-old woman with squamous cell carcinoma (SCC) of the
      tongue with metastasis to the greater trochanter.

PMID- 22647542
TI  - Purification, characterization, and action mode of a chitosanase from
      Streptomyces roseolus induced by chitin.
AB  - Chitosanase (EC3.2.1.132) catalyzes the hydrolysis of beta-1,4-glycosidic bonds
      in chitosan, converting it into chitooligosaccharides, which exhibit versatile
      application potentials in food, pharmaceutical, and agricultural areas. In this
      paper we present a new inducible chitosanase, isolated, and purified from a
      bacterial culture medium of Streptomyces roseolus DH by precipitation with
      ammonium sulfate and combined column chromatographies. The SDS-PAGE results show
      its molecular mass is around 41 kDa, with a purity of more than 95%. The purified
      chitosanase exhibits optimum activity at 50 degrees C, pH 5.0. It is stable
      between 30 and 60 degrees C and at pH values between 5 and 7. It shows the
      highest activity towards colloidal chitosan and breaks down glycol chitosan and
      glycol chitin weakly. The enzyme is significantly inhibited by Cu(2+), Co(2+),
      Mn(2+), Zn(2+), and EDTA, but slightly activated by Mg(2+). Further action mode
      analysis based on chitosan oligomers and a polymer reveals that the chitosanase
      could split chitooligosaccharides with degree of polymerization (DP) >4 and
      chitosan in an endolytic manner. The resultant hydrolytes are mainly
      chitotrisaccharides, indicating it is suitable for the uniform bioconversion of
      chitosan and its derivatives with high efficiency.

PMID- 22647543
TI  - Bench-to-bedside review: Rapid molecular diagnostics for bloodstream infection--a
      new frontier?
AB  - Among critically ill patients, the diagnosis of bloodstream infection poses a
      major challenge. Current standard bacterial identification based on blood culture
      platforms is intrinsically time-consuming and slow. The continuous evolvement of
      molecular techniques has the potential of providing a faster, more sensitive and
      direct identification of causative pathogens without prior need for cultivation.
      This may ultimately impact clinical decision-making and antimicrobial treatment.
      This review summarises the currently available technologies, their strengths and
      limitations and the obstacles that have to be overcome in order to develop a
      satisfactory bedside point-of-care diagnostic tool for detection of bloodstream
      infection. 

PMID- 22647544
TI  - Heterotrimeric G protein-dependent WNT-5A signaling to ERK1/2 mediates distinct
      aspects of microglia proinflammatory transformation.
AB  - BACKGROUND: WNT-5A signaling in the central nervous system is important for
      morphogenesis, neurogenesis and establishment of functional connectivity; the
      source of WNT-5A and its importance for cellular communication in the adult
      brain, however, are mainly unknown. We have previously investigated the
      inflammatory effects of WNT/beta-catenin signaling in microglia in Alzheimer's
      disease. WNT-5A, however, generally recruits beta-catenin-independent signaling.
      Thus, we aim here to characterize the role of WNT-5A and downstream signaling
      pathways for the inflammatory transformation of the brain's macrophages, the
      microglia. METHODS: Mouse brain sections were used for immunohistochemistry.
      Primary isolated microglia and astrocytes were employed to characterize the WNT
      induced inflammatory transformation and underlying intracellular signaling
      pathways by immunoblotting, quantitative mRNA analysis, proliferation and
      invasion assays. Further, measurements of G protein activation by [gamma
      (35)S]GTP binding, examination of calcium fluxes and cyclic AMP production were
      used to define intracellular signaling pathways. RESULTS: Astrocytes in the adult
      mouse brain express high levels of WNT-5A, which could serve as a novel astroglia
      microglia communication pathway. The WNT-5A-induced proinflammatory microglia
      response is characterized by increased expression of inducible nitric oxide
      synthase, cyclooxygenase-2, cytokines, chemokines, enhanced invasive capacity and
      proliferation. Mapping of intracellular transduction pathways reveals that WNT-5A
      activates heterotrimeric G(i/o) proteins to reduce cyclic AMP levels and to
      activate a G(i/o) protein/phospholipase C/calcium-dependent protein
      kinase/extracellular signal-regulated kinase 1/2 (ERK1/2) axis. We show further
      that WNT-5A-induced ERK1/2 signaling is responsible for distinct aspects of the
      proinflammatory transformation, such as matrix metalloprotease 9/13 expression,
      invasion and proliferation. CONCLUSIONS: Thus, WNT-5A-induced and G protein
      dependent signaling to ERK1/2 is important for the regulation of proinflammatory
      responses in mouse primary microglia cells. We show for the first time that WNT
      5A/G protein signaling mediates physiologically important processes in primary
      mammalian cells with natural receptor and G protein stochiometry. Consequently,
      WNT-5A emerges as an important means of astrocyte-microglia communication and we,
      therefore, suggest WNT-5A as a new player in neuroinflammatory conditions, such
      as neurodegenerative disease, hypoxia, stroke, injury and infection.

PMID- 22647545
TI  - Fetal and neonatal germ cell tumors.
AB  - Germ cell tumors (GCTs) arise from the 'germline' - the primordial germ cells
      which are destined to become either the egg or the sperm. GCTs can be challenging
      to understand because their intrinsic pluripotency results in a wide spectrum of
      histologies and biologic behaviors. However, the histology of GCTs in the fetus
      and neonate is more restricted and the clinical spectrum more narrow than when
      these tumors occur later in life. GCTs in the fetus and neonate are predominately
      mature and immature teratomas, usually curable with surgery alone. And, given the
      efficacy of cisplatin-based regimens in GCTs, cure is likely even for those
      patients whose tumors contain the more malignant histologies, which in the
      neonate is usually yolk sac tumor. Recent advances in understanding the
      underlying aberrations in germline development continue to shed light on the
      genesis of these tumors and possible new avenues for treatment.

PMID- 22647546
TI  - Therapy management with sunitinib in patients with metastatic renal cell
      carcinoma: key concepts and the impact of clinical biomarkers.
AB  - Targeted agents have improved prognosis for patients with metastatic renal cell
      carcinoma (mRCC), and they are changing therapeutic expectations with respect to
      long-term clinical outcomes for these patients. However, in order to obtain the
      maximum clinical benefit from targeted agents, effective therapy management is
      essential and includes optimization of dosing and treatment duration, as well as
      adequate side-effect management. Sunitinib has demonstrated efficacy for the
      treatment of patients with mRCC and is a reference standard of care for first
      line therapy. However, in clinical practice, it is difficult to determine the
      best treatment strategy with targeted agents due to long-term tolerability and
      the development of resistance. An individualized therapeutic strategy in RCC
      requires a comprehensive understanding of the biology of response and resistance
      to targeted therapy. Here we review the clinical data regarding the efficacy and
      safety for sunitinib and highlight the importance of therapy management, as well
      as the potential use of clinical biomarkers in order to maximize the clinical
      benefit from sunitinib treatment in patients with mRCC.

PMID- 22647548
TI  - Metal immobilization and soil amendment efficiency at a contaminated sediment
      landfill site: a field study focusing on plants, springtails, and bacteria.
AB  - Metal immobilization may contribute to the environmental management strategy of
      dredged sediment landfill sites contaminated by metals. In a field experiment,
      amendment effects and efficiency were investigated, focusing on plants,
      springtails and bacteria colonisation, metal extractability and sediment
      ecotoxicity. Conversely to hydroxylapatite (HA, 3% DW), the addition of Thomas
      Basic Slag (TBS, 5% DW) to a 5-yr deposited sediment contaminated with Zn, Cd,
      Cu, Pb and As resulted in a decrease in the 0.01 M Ca(NO(3))(2)-extractable
      concentrations of Cd and Zn. Shoot Cd and Zn concentration in Calamagrostis
      epigejos, the dominant plant species, also decreased in the presence of TBS. The
      addition of TBS and HA reduced sediment ecotoxicity and improved the growth of
      the total bacterial population. Hydroxylapatite improved plant species richness
      and diversity and decreased antioxidant enzymes in C. Epigejos and Urtica dioica.
      Collembolan communities did not differ in abundance and diversity between the
      different treatments.

PMID- 22647547
TI  - Compromised autophagy by MIR30B benefits the intracellular survival of
      Helicobacter pylori.
AB  - Helicobacter pylori evade immune responses and achieve persistent colonization in
      the stomach. However, the mechanism by which H. pylori infections persist is not
      clear. In this study, we showed that MIR30B is upregulated during H. pylori
      infection of an AGS cell line and human gastric tissues. Upregulation of MIR30B
      benefited bacterial replication by compromising the process of autophagy during
      the H. pylori infection. As a potential mechanistic explanation for this
      observation, we demonstrate that MIR30B directly targets ATG12 and BECN1, which
      are important proteins involved in autophagy. These results suggest that
      compromise of autophagy by MIR30B allows intracellular H. pylori to evade
      autophagic clearance, thereby contributing to the persistence of H. pylori
      infections.

PMID- 22647549
TI  - Invasive salivary duct carcinoma ex pleomorphic adenoma of the parotid gland: a
      teaching case giving rise to the genuine diagnostic difficulty on an inadequate
      cytology specimen.
AB  - A history of a recent rapid increase in long-standing swelling mass was presented
      in the right parotid gland of an 85-year-old male. The inadequate cytologic
      specimens contained few small clusters of three-dimensional malignant epithelial
      cells having hyperchromatic pleomorphic nuclei and prominent nucleoli, adjacent
      to a cluster of benign monomorphic myoepithelial cells. We first interpreted it
      merely as an adenocarcinoma, not otherwise specified. A radical parotidectomy was
      performed, and gross examination revealed an encapsulated and firm tumor lesion,
      looking grayish-blue to yellowish-white, focally associated with extracapsular
      invasion. On microscopic examination, the tumor was predominantly composed of a
      proliferation of highly atypical epithelial cells having abundant eosinophilic
      cytoplasm, often arranged in a Roman-bridge appearance with foci of comedo
      necrosis, alternating with extensive infiltration to adjacent stroma in a
      trabecular or alveolar fashion with severe vessel permeation. Within the
      background of pleomorphic adenoma, the carcinoma cells sometimes replaced ductal
      luminal cells while retaining an intact-like myoepithelial layer. Therefore, we
      finally made a diagnosis of invasive salivary duct carcinoma ex pleomorphic
      adenoma. We should be aware that owing to its characteristic features,
      cytopathologists might be able to determine correct diagnosis, based on multiple
      and adequate samplings. VIRTUAL SLIDES: The virtual slide(s) for this article can
      be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2126158270695815.

PMID- 22647550
TI  - Physician do no harm.

PMID- 22647551
TI  - Molecular chaperone heat shock protein 70 participates in the labile phase of the
      development of behavioural sensitization induced by a single morphine exposure in
      mice.
AB  - De-novo protein synthesis is required in the development of behavioural
      sensitization. A prior screening test from our laboratory has implicated heat
      shock protein 70 (Hsp70) as one of the proteins required in this behavioural
      plasticity. Thus, this study was designed to extend our understanding of the role
      of Hsp70 in the development of behavioural sensitization induced by a single
      morphine exposure in mice. First, by employing transcription inhibitor
      actinomycin D (AD) and protein synthesis inhibitor cycloheximide (CHX), we
      identified a protein synthesis-dependent labile phase (within 4 h after the first
      morphine injection) in the development of behavioural sensitization to a single
      morphine exposure. Second, Hsp70 protein expression in the nucleus accumbens
      correlated positively with locomotor responses of sensitized mice and, more
      importantly, the expression of Hsp70 increased within 1 h after the first
      morphine injection. Third, AD and CHX both prevented expression of Hsp70 and
      disrupted the development of the single morphine induced behavioural
      sensitization, which further implied Hsp70 was highly associated with behavioural
      sensitization. Finally, the selective Hsp70 inhibitor pifithrin-MU (PES) i.c.v.
      injected in mice prevented the development of behavioural sensitization and,
      critically, this inhibitory effect occurred only when PES was given within 1 h
      after the first morphine injection, which was within the labile phase of the
      development period. Taken together, we draw the conclusion that Hsp70 is
      crucially involved in the labile phase of the development of behavioural
      sensitization induced by a single morphine exposure, probably functioning as a
      molecular chaperone.

PMID- 22647552
TI  - Age-related differences in hepatic ischemia/reperfusion: gene activation, liver
      injury, and protective effect of melatonin.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) causes functional and structural damage to
      liver cells, this being more pronounced with increasing age of the tissue.
      Melatonin is a pineal indole that has been shown to play an important role as a
      free radical scavenger and anti-inflammatory molecule. MATERIAL AND METHODS: The
      age-dependent responses to I/R were compared in 2-mo-old and 14-mo-old male
      Wistar rats. After 35 min of hepatic ischemia followed by 36 h of reperfusion,
      rats were sacrificed. Sham-operated control rats underwent the same protocol
      without real vascular occlusion. Animals were intraperitoneally injected with 10
      mg/kg melatonin 24 h before the operation, at the time of surgery, and 12 and 24
      h after it. The tissues were submitted to histopathologic evaluation. The levels
      of ALT and AST were analyzed in plasma. The expression of TNF-alpha, IL-1beta, IL
      10, MCP-1, IFN-gamma, iNOS, eNOS, Bad, Bax, Bcl2, AIF, PCNA, and NFKB1 genes were
      detected by RT-PCR in hepatic tissue. RESULTS: I/R was associated with
      significant increases in the expression of pro-inflammatory and pro-apoptotic
      genes in liver. Older rats submitted to I/R were found to respond with increased
      liver damage as compared with young rats, with serum ALT and AST levels
      significantly higher than in young animals. Mature rats also showed more evident
      increases in expression of pro-inflammatory cytokines (IL-1beta, MCP-1, and IFN
      gamma) as well as a decrease in the mRNA expression of IL-10 as compared with
      young animals. Pro-apoptotic genes (Bax, Bad, and AIF) were significantly
      enhanced in liver after I/R, without differences between young and mature
      animals. However, the expression of Bcl2 gene did not show any change. Melatonin
      treatment was able to lower the expression of pro-inflammatory cytokines and pro
      apoptotic genes and to improve liver function, as indicated by normalization of
      plasma AST and ALT levels and by reduction of necrosis and microsteatosis areas.
      CONCLUSIONS: Melatonin treatment was able to reduce the I/R-stimulated pro
      inflammatory and pro-apoptotic genes in the rat liver. Since older animals showed
      a more marked increase in inflammation and in liver injury, the treatment was
      more effective in those subjects.

PMID- 22647553
TI  - Comparative effectiveness of population interventions to improve access to
      reperfusion for ST-segment-elevation myocardial infarction in Australia.
AB  - BACKGROUND: Improving timely access to reperfusion is a major goal of ST-segment
      elevation myocardial infarction care. We sought to compare the population impact
      of interventions proposed to improve timely access to reperfusion therapy in
      Australia. METHODS AND RESULTS: Australian hospitals, population, and road
      network data were integrated using Geographical Information Systems. Hospitals
      were classified into those that provided primary percutaneous coronary
      intervention (PPCI) or fibrinolysis. Population impact of interventions proposed
      to improve timely access to reperfusion (PPCI, fibrinolysis, or both) were
      modeled and compared. Timely access to reperfusion was defined as the proportion
      of the population capable of reaching a fibrinolysis facility <=60 minutes or a
      PPCI facility <=120 minutes from emergency medical services activation. The
      majority (93.2%) of the Australian population has timely access to reperfusion,
      mainly (53%) through fibrinolysis. Only 40.2% of the population had timely access
      to PPCI, and access to PPCI services is particularly limited in regional and
      nonexistent in remote areas. Optimizing the emergency medical services' response
      or increasing PPCI services resulted in marginal improvement in timely access
      (1.8% and 3.7%, respectively). Direct transport to PPCI facilities and
      interhospital transfer for PPCI improves timely access to PPCI for 19.4% and
      23.5% of the population, respectively. Prehospital fibrinolysis markedly improved
      access to timely reperfusion in regional and remote Australia. CONCLUSIONS:
      Significant gaps in timely provision of reperfusion remain in Australia.
      Systematic implementation of changes in service delivery has potential to improve
      timely access to PPCI for a majority of the population and improve access to
      fibrinolysis to those living in regional and remote areas.

PMID- 22647554
TI  - Classification of inflammatory bowel disease:  the old and the new.
AB  - PURPOSE OF REVIEW: Inflammatory bowel diseases (IBDs) are disorders of
      multifactorial cause that present as a multitude of phenotypes, clinical
      behaviours and severity. Crohn's disease and ulcerative colitis are considered as
      the two extremes of what is believed to be a spectrum of chronic gut inflammation
      and this separation is still the first classification used when confronted with
      an IBD patient. An accurate classification within IBD has several benefits, with
      respect to patient counselling, assessing risk for disease progression, and
      particularly with respect to choosing the most appropriate therapy for an
      individual patient. Basic scientists on the other hand prefer classifications
      that would allow to better understand the pathophysiology of the different
      manifestations of Crohn's disease and ulcerative colitis. RECENT FINDINGS:
      Attempts to reclassify IBD based on recent genetic, serologic or immunologic
      findings have been made. Most, however, have not been translated to daily
      practice and need confirmation first. SUMMARY: Clinicians should apply a
      systematic approach to their patients by using existing phenotypic
      classifications such as Montreal or Paris. They should further recognize clinical
      and endoscopic features of bad outcome such as perianal disease, deep ulcers on
      colonoscopy and extensive small bowel involvement.

PMID- 22647555
TI  - Integration of podiatric surgery within an orthopaedic department: an audit of
      patient satisfaction with labour force implications.
AB  - BACKGROUND: Podiatric surgery is well established in the National Health Service
      (NHS) in the UK with over 50 podiatric surgery units. This paper aimed to
      evaluate patient experience and satisfaction following foot surgery within a NHS
      orthopaedic department before and after the appointment of a podiatric surgeon.
      It highlights relevant labour force issues. METHODOLOGY: 88 patients operated on
      by a podiatric surgeon were asked to complete an anonymous foot surgery
      satisfaction questionnaire. The same questionnaire was sent to another random
      selection of 88 orthopaedic patients matched by Office of Population, Censuses
      and Surveys Classification of Surgical Operations and Procedures code (OPCS).
      RESULTS: Of the 88 questionnaires sent to each group 56 (63.6%) were returned to
      the (podiatric group) and 60 (68.2%) the (orthopaedic). Patient satisfaction was
      rated as excellent 63.7%, moderate/good 23.6% and poor 12.7% of podiatric
      respondents and excellent 43.4%, moderate 17% and poor 39.6% of orthopaedic
      respondents. CONCLUSION: The results suggest that patient satisfaction following
      foot surgery rose significantly following appointment of a podiatric surgeon.
      Improvements were identified in the overall outcome of the surgery and other
      aspects of the patients' journey. To date we are not aware of any study that has
      reviewed outcomes of an integrated approach and, as such provides a historical
      benchmark.

PMID- 22647556
TI  - Seasonal variation in the incidence rate of tuberculous meningitis is associated
      with sunshine hours.
AB  - Tuberculous meningitis (TBM) is a severe complication of tuberculosis and occurs
      mainly during early childhood. The incidence rate of TBM varies with season, and
      serum vitamin D levels, which are dependent on sunlight, might play a role. We
      studied the association between TBM incidence rate and hours of sunshine in Cape
      Town, South Africa and found a significant association between the incidence rate
      of TBM and hours of sunshine 3 months earlier (incidence rate ratio per 100
      sunshine hours 0.69, 95% confidence interval 0.54-0.88, P = 0.002). The
      association supports the hypothesis that vitamin D might play a role in the
      pathophysiology of TBM. Further prospective studies in which vitamin D status is
      measured are necessary to determine causality.

PMID- 22647557
TI  - Seasonal performance of a malaria rapid diagnosis test at community health
      clinics in a malaria-hyperendemic region of Burkina Faso.
AB  - BACKGROUND: Treatment of confirmed malaria patients with Artemisinin-based
      Combination Therapy (ACT) at remote areas is the goal of many anti-malaria
      programs. Introduction of effective and affordable malaria Rapid Diagnosis Test
      (RDT) in remote areas could be an alternative tool for malaria case management.
      This study aimed to assess performance of the OptiMAL dipstick for rapid malaria
      diagnosis in children under five. METHODS: Malaria symptomatic and asymptomatic
      children were recruited in a passive manner in two community clinics (CCs).
      Malaria diagnosis by microscopy and RDT were performed. Performance of the tests
      was determined. RESULTS: RDT showed similar ability (61.2%) to accurately
      diagnose malaria as microscopy (61.1%). OptiMAL showed a high level of
      sensitivity and specificity, compared with microscopy, during both transmission
      seasons (high & low), with a sensitivity of 92.9% vs. 74.9% and a specificity of
      77.2% vs. 87.5%. CONCLUSION: By improving the performance of the test through
      accurate and continuous quality control of the device in the field, OptiMAL could
      be suitable for use at CCs for the management and control of malaria.

PMID- 22647558
TI  - Interprofessional SDM train-the-trainer program "Fit for SDM": provider
      satisfaction and impact on participation.
AB  - OBJECTIVE: The aim of the study was to evaluate the interprofessional SDM
      training program "Fit for SDM" in medical rehabilitation, which was implemented
      in two steps: (1) university staff trained providers in executive positions as
      trainers and (2) the providers trained their staff. METHODS: For the evaluation
      of the first step a questionnaire for shared decision-making (SDM) skills and
      satisfaction with the training was completed by the providers in executive
      positions. A staff survey was used in a cluster-randomized controlled study to
      determine the overall impact of the train-the-trainer program on internal and
      external participation in the team. RESULTS: The providers in the six clinics
      evaluated their SDM competences and satisfaction very positively after training
      (step 1). External participation was enhanced by application of the training
      content, with significant changes recorded for females and nurses in particular.
      However, it had no direct influence on internal participation. CONCLUSIONS: This
      is the first interprofessional SDM train-the-trainer program in Germany to bridge
      interprofessionalism (internal participation) and SDM (external participation);
      it was implemented successfully and evaluated positively. PRACTICE IMPLICATIONS:
      Establishing interprofessional SDM training programs should be encouraged for all
      health care professionals. Implementation in the interprofessional setting should
      consider interprofessional team factors.

PMID- 22647559
TI  - Effects of left ventricular assist device (LVAD) placement on myocardial
      oxidative stress markers.
AB  - PURPOSE: The primary purpose of this study was to examine the changes in
      myocardial oxidative stress during the support of a left ventricular assist
      device (LVAD). METHODS: Myocardial tissue was collected from the lower left
      ventricle of 15 adult subjects with class IV heart failure (HF) during LVAD
      placement (n=9) or LVAD removal (Post-LVAD; n=6). Each tissue sample was
      separated into cytosolic and myofibrillar subfractions and analysed for protein
      content and carbonylation. RESULTS: The myofibrillar proteins in the HF subjects
      had a significantly lower (p=0.008) level of protein carbonylation when compared
      to the myofibrillar proteins in Post-LVAD patients at 1.630+/-0.277 and 3.075+/
      0.413 optical density, respectively. The level of protein carbonylation in myosin
      and actin were lower in HF (myosin: 1406.22+/-218.45, actin: 436+/-79.72 optical
      density) subjects compared to Post-LVAD (myosin: 2280.5+/-441.26, actin: 804.67+/
      155.71 optical density) subjects (p=0.035 and p=0.018, respectively). However,
      once the extent of carbonylation in the myosin and actin bands were normalised to
      the amount of protein content, all significant difference was lost (HF moysin:
      1823.89+/-413.42, Post-LVAD myosin: 1330.33+/-297.10 optical density, p=0.199 and
      HF actin: 3755.78+/-349.59, Post-LVAD actin: 4402.83+/-666.51 optical density,
      p=0.182). There was no significant difference in the cytosolic subfractions
      before or after normalisation of protein content. CONCLUSION: Carbonylation is
      elevated in the myocardium of HF and Post-LVAD subjects and it appears that LVAD
      support does not affect the level of myocardial oxidative stress.

PMID- 22647560
TI  - Does treatment of SDB in children improve cardiovascular outcome?
AB  - Sleep disordered breathing (SDB) is a common disorder in both adults and children
      and is caused by the obstruction of the upper airway during sleep. Unlike adults,
      most cases of paediatric SDB are due to the presence of enlarged tonsils and
      adenoids, thus the main treatment option is adenotonsillectomy (T&A). It is well
      known that obstructive sleep apnoea in adults increases the risk for
      hypertension, coronary artery disease and stroke, and there is now mounting
      evidence that SDB also has a significant impact on the cardiovascular system in
      children with reports of elevated blood pressure, endothelial dysfunction and
      altered autonomic cardiovascular control. As there is now substantial evidence
      that elevated blood pressure in childhood is carried on to adulthood it is
      important to know if treatment of SDB improves cardiovascular outcomes. Studies
      in adults have shown that treatment of SDB leads to improvements in
      cardiovascular function, including a reduction in pulmonary artery pressure,
      systemic blood pressure and endothelial dysfunction. However, studies exploring
      the outcomes of treatment of SDB in children on the cardiovascular system are
      limited and varied in their methodology and outcome measures. As a number of
      cardiovascular disturbances are sequelae of SDB, early detection and management
      could result in the reduction of elevated blood pressure in children, and
      consequently a reduction in cardiovascular morbidity in adulthood. The aim of
      this review is to summarise the findings of studies to date which have
      investigated the cardiovascular outcomes in children treated for SDB and to make
      recommendations for future management of this very common disease.

PMID- 22647561
TI  - Clinical validation of a new thermodilution system for the assessment of cardiac
      output and volumetric parameters.
AB  - INTRODUCTION: Transpulmonary thermodilution is used to measure cardiac output
      (CO), global end-diastolic volume (GEDV) and extravascular lung water (EVLW). A
      system has been introduced (VolumeView/EV1000TM system, Edwards Lifesciences,
      Irvine CA, USA) that employs a novel algorithm for the mathematical analysis of
      the thermodilution curve. Our aim was to evaluate the agreement of this method
      with the established PiCCOTM method (Pulsion Medical Systems SE, Munich, Germany,
      clinicaltrials.gov identifier: NCT01405040) METHODS: Seventy-two critically ill
      patients with clinical indication for advanced hemodynamic monitoring were
      included in this prospective, multicenter, observational study. During a 72-hour
      observation period, 443 sets of thermodilution measurements were performed with
      the new system. These measurements were electronically recorded, converted into
      an analog resistance signal and then re-analyzed by a PiCCO2TM device (Pulsion
      Medical Systems SE). RESULTS: For CO, GEDV, and EVLW, the systems showed a high
      correlation (r(2) = 0.981, 0.926 and 0.971, respectively), minimal bias (0.2
      L/minute, 29.4 ml and 36.8 ml), and a low percentage error (9.7%, 11.5% and
      12.2%). Changes in CO, GEDV and EVLW were tracked with a high concordance between
      the two systems, with a traditional concordance for CO, GEDV, and EVLW of 98.5%,
      95.1%, and 97.7% and a polar plot concordance of 100%, 99.8% and 99.8% for CO,
      GEDV, and EVLW, respectively. Radial limits of agreement for CO, GEDV and EVLW
      were 0.31 ml/minute, 81 ml and 40 ml, respectively. The precision of GEDV
      measurements was significantly better using the VolumeViewTM algorithm compared
      to the PiCCOTM algorithm (0.033 (0.03) versus 0.040 (0.03; median (interquartile
      range), P = 0.000049). CONCLUSIONS: For CO, GEDV, and EVLW, the agreement of both
      the individual measurements as well as measurements of change showed the
      interchangeability of the two methods. For the VolumeView method, the higher
      precision may indicate a more robust GEDV algorithm. TRIAL REGISTRATION:
      clinicaltrials.gov NCT01405040.

PMID- 22647562
TI  - Contextualization of HIV and HPV risk and prevention among Pacific Islander young
      adults in Southern California.
AB  - HIV and sexually transmitted human papillomavirus (HPV) are associated with each
      other and with the development of comorbid cancer. Current epidemiology indicates
      that among Pacific Islanders in the United States, young adults are at highest
      risk of HIV and HPV. In our inductive community based participatory research
      study, we used focus groups and key informant interviews (March-August 2010) with
      young adults, parents, community leaders, and providers (n = 95) to identify and
      contextualize factors that shape HIV and HPV risk and prevention among young
      adults in Chamorro and Tongan communities in Southern California. We identified
      nine themes that incorporated the following principal factors: misinformation and
      otherization; dominant concerns regarding premarital pregnancy; restricted
      intergenerational communication; family shame and privacy; gendered
      manifestations of religio-cultural norms; barriers impeding access to sexual
      health resources; parents' role in prevention; community vs. individual
      responsibility; and family and ethnic pride. Our thematic findings fit well with
      Rhodes' "risk and enabling environment" heuristic (2009), which we used to
      contextualize risk and prevention at micro and macro levels of physical, social,
      economic, and policy environments. We propose the addition of a separate cultural
      environment to the heuristic and conclude that a focus on applying individual and
      community agency at the micro-level would be an approachable starting point for
      intervention for our local Pacific Islander communities and groups in similar
      ecological contexts globally. Enhanced community-led education programs and
      engagement of religious and other community leaders to facilitate
      intergenerational communication could counteract taboos that obstruct prevention.

PMID- 22647563
TI  - Socioeconomic equity in amenable mortality in Finland 1992-2008.
AB  - This study presents an approach to assess socioeconomic equity in the
      effectiveness of health services. As an indicator of health system performance we
      use amenable mortality which captures premature deaths that should not occur in
      the presence of effective and timely health care. Data on amenable deaths by
      income groups in Finland in 1992-2008 came from the National Causes of Death
      Register which was linked to sociodemographic data in population registers. We
      evaluate the extent of and trends in socioeconomic differences with two widely
      used inequity indices, the concentration index and the slope index of inequality,
      and also for different categories of amenable mortality. By categorizing
      conditions according to the level of intervention associated with the conditions
      it is possible to evaluate the effect of types of health interventions. Causes of
      death attributable to specialized and primary care interventions comprise the
      main groups. By this approach of decomposing equity in amenable mortality in
      Finland we detected major and increasing socioeconomic inequities and also
      greater inequity among deaths amenable to specialized health care interventions.
      Moreover, we saw that inequity increased at a faster pace among deaths amenable
      to specialized health care interventions yet primary health care interventions
      made a greater contribution to overall inequity. Although the overall rate of
      amenable mortality decreased notably during the follow-up, the time trends of
      socioeconomic differences in amenable health care indicate a substantial increase
      in inequities in health care in Finland.

PMID- 22647565
TI  - Revisiting "her" infertility: medicalized embodiment, self-identification and
      distress.
AB  - Prior research emphasizes women's distress and responsibility for a couple's
      infertility because of gendered, pronatalist norms. Yet some studies suggest that
      being personally diagnosed and/or undergoing treatment differentially shapes
      reactions. We focused on differences in women's experiences with diagnosis and
      treatment, conceptualized as the medicalized embodiment of infertility. Using
      regression analysis, we examined two psychosocial outcomes (self-identification
      as infertile and fertility-specific distress) in a sample of 496 heterosexual,
      U.S. women from the National Survey of Fertility Barriers. Medicalized embodiment
      was salient to women's reactions, but had different relationships to self
      identification versus distress. Although women experienced distress regardless of
      type of diagnosis, they were generally less likely to self-identify as infertile
      unless personally diagnosed. As such, we cannot assume that all women universally
      experience infertility. Future research should also address self-identification
      and distress as separate as opposed to simultaneous psychosocial outcomes.

PMID- 22647564
TI  - Moving towards culturally competent health systems: organizational and market
      factors.
AB  - Cultural competency has been proposed as an organizational strategy to address
      racial/ethnic disparities in the healthcare system; disparities are a long
      standing policy challenge whose relevance is only increasing with the increasing
      population diversity of the US and across the world. Using an integrative
      conceptual framework based on the resource dependency and institutional theories,
      we examine the relationship between organizational and market factors and
      hospitals' degree of cultural competency. Our sample consists of 119 hospitals
      located in the state of California (US) and is constructed using the following
      datasets for the year 2006: Cultural Competency Assessment Tool of Hospitals
      (CCATH) Survey, California's Office of Statewide Health Planning & Development's
      Hospital Inpatient Discharges and Annual Hospital Financial Data, American
      Hospital Association's Annual Survey, and the Area Resource File. The dependent
      variable consists of the degree of hospital cultural competency, as assessed by
      the CCATH overall score. Organizational variables include ownership status,
      teaching hospital, payer mix, size, system membership, financial performance, and
      the proportion of inpatient racial/ethnic minorities. Market characteristics
      included hospital competition, the proportion of racial/ethnic minorities in the
      area, metropolitan area, and per capita income. Regression analyses were
      conducted to assess the relationship between the CCATH overall score and
      organizational and market variables. Our results show that hospitals which are
      not-for-profit, serve a more diverse inpatient population, and are located in
      more competitive and affluent markets exhibit a higher degree of cultural
      competency. Our results underscore the importance of both institutional and
      competitive market pressures in guiding hospital behavior. For instance, while
      not-for-profit may adopt innovative/progressive policies like cultural competency
      simply as a function of their organizational goals, linking cultural competency
      with organizational performance may be essential to attract more profit driven
      hospitals.

PMID- 22647566
TI  - [Gallbladder metastasis from renal cell carcinoma, an extremely rare neoplastic
      dissemination location].

PMID- 22647568
TI  - Reconstruction of vermilion deficiencies: the running V-flap technique.
AB  - Notching, or 'whistle deformity', is a common vermilion deformity among patients
      with cleft lips. Vermilion volume deficiency may also be present secondary to
      trauma or tumour excision. Herein, we present a new flap model to repair such
      vermilion deformities. Six patients were included in the study. Running V-flaps
      prepared from the oral mucosa were used. While the underlying cause of vermilion
      deficiency was cleft-lip surgery in four of the patients, the indication for
      surgery was trauma related in two patients. In all patients, the volume
      deficiency was corrected. No patient exhibited scarring, colour mismatch or
      asymmetry. We believe that our new flap model can be a reliable alternative in
      secondary vermilion deficiencies.

PMID- 22647567
TI  - Preoperative asymmetry of upper eyelid thickness in young Chinese women
      undergoing double eyelid blepharoplasty.
AB  - Asymmetry of the eyelid crease is a major complication following double eyelid
      blepharoplasty; the reasons are multivariate. This study presents, for the first
      time, a novel method, based on high-definition magnetic resonance imaging and
      high-precision weighing of tissue, for quantitating preoperative asymmetry of
      eyelid thickness in young Chinese women presenting for blepharoplasty. From 1
      January 2008 to 1 October 2011, we studied 1217 women requesting double eyelid
      blepharoplasty. The patients ranged in age from 17 to 24 years (average 21.13
      years). All patients were of Chinese Han nationality. Soft-tissue thickness at
      the tarsal plate superior border was 5.05 +/- 1.01 units on the right side and
      4.12 +/- 0.96 units on the left. The submuscular fibro-adipose tissue area was
      95.12 +/- 23.27 unit(2) on the right side and 76.05 +/- 21.11 unit(2) on the
      left. The pre-aponeurotic fat pad area was 112.33 +/- 29.16 unit(2) on the right
      side and 91.25 +/- 27.32 unit(2) on the left. The orbicularis muscle resected
      weighed 0.185 +/- 0.055 g on the right side and 0.153 +/- 0.042 g on the left;
      the orbital fat resected weighed 0.171 +/- 0.062 g on the right side and 0.106 +/
      0.057 g on the left. In conclusion, upper eyelid thickness asymmetry is a common
      phenomenon in young Chinese women who wish to undertake double eyelid
      blepharoplasty. We have demonstrated that the orbicularis muscle and orbital fat
      pad are consistently thicker on the right side than on the left.

PMID- 22647569
TI  - Comparison of pedicled and free anterolateral thigh flaps for reconstruction of
      complex defects of the abdominal wall: review of 20 consecutive cases.
AB  - BACKGROUND: The reconstruction of large, complex defects of the abdominal wall
      after the ablation of malignant tumours can be challenging. The transfer of an
      anterolateral thigh (ALT) flap is an attractive option. This study compared free
      ALT flaps and pedicled ALT flaps for abdominal wall reconstruction. METHODS: From
      1996 through 2011, 20 patients underwent abdominal wall reconstruction with ALT
      flaps. The flaps were pedicled in 12 patients and free in eight patients. Medical
      records were reviewed for complications and clinical and demographic data.
      Abdominal wall defects were classified into the following four groups: upper
      midline, lower midline, upper quadrants and lower quadrants. RESULTS: Pedicled
      flaps were transferred to the upper midline region in one patient, the lower
      midline region in six patients and lower quadrants in five patients. Free flaps
      were transferred to the lower midline region in two patients, upper quadrants in
      four patients and lower quadrants in two patients. Mean reconstructive time was
      significantly longer with free flaps (6 h 32 min) than with pedicled flaps (4 h
      55 min, p = 0.035). Although free flaps (mean size, 360 cm(2)) were larger than
      pedicled flaps (mean size, 289 cm(2)), the difference was not significant (p =
      0.218). The rates of complications did not differ between free flaps and pedicled
      flaps. No total flap loss occurred, and there was partial loss of only a single
      pedicled flap, which was the flap furthest from the pivot point. Infections
      developed of two pedicled flaps and three free flaps. CONCLUSION: This study
      suggests that complication rates do not differ between free and pedicled ALT
      flaps. The choice of flap depends on the size and location of the defect and the
      length of the vascular pedicle.

PMID- 22647570
TI  - Spontaneous auricular seroma.
AB  - We present a case of spontaneous seroma of the ear, which can be encountered in
      the plastic surgery clinic. We describe our management and briefly review the
      literature regarding this interesting condition.

PMID- 22647571
TI  - Epithelioid hemangioendothelioma: occasionally encountered and potentially
      harmful.
AB  - Epithelioid hemangioendothelioma (EH) is a rare neoplasm which can arise from any
      vascularised tissue and has the potential to metastasise. Correct diagnosis can
      be challenging as it has a variety of presentations and can mimic other
      pathology. We present a case arising from the brachial artery at the level of the
      antecubital fossa. Incision biopsies showed benign fatty tissue only; leading to
      delayed diagnosis, delayed excision and prolonged patient discomfort. This case
      shows the importance of exercising clinical judgement as negative incision
      biopsies were, with hindsight, not representative of the lesion.

PMID- 22647572
TI  - Complete mapping of lateral and medial sural artery perforators: anatomical study
      with Duplex-Doppler ultrasound correlation.
AB  - INTRODUCTION: The precise vascular anatomy of posterior lower leg skin is not
      well understood. Despite being a potential donor site for sural artery perforator
      flaps, this region is rarely used and underestimated. The aim of this study was
      to provide exact preoperative planning for medial and lateral sural artery
      perforator flap harvest. METHODS: An anatomical study on 16 cadaveric lower legs
      was performed to determine the number and location of all medial and lateral
      sural artery perforators in relation to five fixed points (medial and lateral
      maleolus, calcaneus, medial and lateral condyle). A Duplex study on 32 lower legs
      determined the number and location of dominant medial and lateral sural artery
      perforators in relation to same anatomical points. Results of the two studies
      were correlated. RESULTS: A total of 234 perforators were found in the anatomical
      (134) and Duplex studies (100). A dominant lateral sural artery perforator was
      found in 9.4% of all lateral perforators in 31% of dissected legs. A dominant
      medial sural artery perforator was found in 37% of all medial perforators in 94%
      of legs. The difference in the number of dominant medial and lateral perforators
      was significant (p < 0.001) in the anatomical study, while no significant
      difference was found in the Duplex study (p = 0.920). CONCLUSION: The anatomical
      study showed relative unreliability of sural region regarding number of dominant
      perforators. Therefore, harvest of medial and particularly lateral sural artery
      perforator flap is unsafe without preoperative perforator mapping. No significant
      difference in location of dominant perforators was found between Duplex and
      anatomical studies. Duplex proved reliable for planning of sural artery
      perforator flaps due to high precision in detecting location of dominant
      perforators.

PMID- 22647573
TI  - Functional reconstruction of total lower lip defects using innervated gracilis
      flap in the setting of high-energy ballistic injury to the lower face:
      preliminary report.
AB  - BACKGROUND: Reconstruction of total full-thickness lower lip defects combined
      with extensive composite mandibular defects particularly in the setting of close
      range high-energy ballistic injury presents a formidable challenge for the
      reconstructive plastic surgeon. While the fibular flap has been widely accepted
      for its usefulness in the reconstruction of composite mandibular defects, to
      date, there is no definitive widely established method of total lower lip
      reconstruction. The article presents authors' approach using innervated gracilis
      muscle flap for total lower lip reconstruction in the setting of high-energy
      gunshot injuries to the face. METHODS: Three patients underwent composite
      mandibular defect reconstruction using fibular osteocutaneous flap and functional
      lower lip reconstruction using innervated gracilis muscle flap. Lip lining was
      reconstructed using the skin paddle of the fibular flap. The external surface of
      the gracilis muscle was skin-grafted. Facial artery myomucosal flap provided
      vermilion reconstruction in two patients. RESULTS: All fibular (n=3) and gracilis
      flap transfers (n=3) were viable. An electromyographic study at 1 year
      postoperatively demonstrated successful re-innervation of the gracilis muscle.
      Starting at about 10 weeks postoperatively, patients exhibited voluntary lip
      movements and oral competence. In addition, all patients achieved near-normal
      speech, evidence of recovered protective sensitivity and satisfactory appearance.
      The mean follow-up was 16.1 months. CONCLUSIONS: Our preliminary report in three
      patients demonstrated that innervated gracilis muscle transfer combined with
      fibular flap provides a successful reconstruction of extensive composite
      mandibular and total lower lip defects resulting from gunshot injuries to the
      face. Oral continence was achieved by combination of regained tonicity and
      voluntary movement of the gracilis muscle following re-innervation and assistance
      of the cheek muscles on the gracilis muscle. The described technique was reliable
      and the results were promising.

PMID- 22647575
TI  - Eye gaze metrics reflect a shared motor representation for action observation and
      movement imagery.
AB  - Action observation (AO) and movement imagery (MI) have been reported to share
      similar neural networks. This study investigated the congruency between AO and MI
      using the eye gaze metrics, dwell time and fixation number. A simple reach-grasp
      place arm movement was observed and, in a second condition, imagined where the
      movement was presented from the first person perspective (1PP) and the third
      person perspective (3PP). Dwell time and number of fixations were calculated for
      whole scene and regions of interest (ROIs). For whole scene, no significant
      differences were found in the number of fixations for condition (AO, MI) or
      perspective. Dwell time, however, was significantly longer in AO than MI. For
      ROIs, the number of fixations was significantly greater in 1PP than 3PP. The data
      provide support for congruence between motor simulation states but also indicate
      some functional differences.

PMID- 22647574
TI  - CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon
      intranasal delivery.
AB  - BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease of the central
      nervous system (CNS). In the murine experimental autoimmune encephalomyelitis
      (EAE) model of MS, T regulatory (Treg) cell therapy has proved to be beneficial,
      but generation of stable CNS-targeting Tregs needs further development. Here, we
      propose gene engineering to achieve CNS-targeting Tregs from naive CD4 cells and
      demonstrate their efficacy in the EAE model. METHODS: CD4+ T cells were modified
      utilizing a lentiviral vector system to express a chimeric antigen receptor (CAR)
      targeting myelin oligodendrocyte glycoprotein (MOG) in trans with the murine
      FoxP3 gene that drives Treg differentiation. The cells were evaluated in vitro
      for suppressive capacity and in C57BL/6 mice to treat EAE. Cells were
      administered by intranasal (i.n.) cell delivery. RESULTS: The engineered Tregs
      demonstrated suppressive capacity in vitro and could efficiently access various
      regions in the brain via i.n cell delivery. Clinical score 3 EAE mice were
      treated and the engineered Tregs suppressed ongoing encephalomyelitis as
      demonstrated by reduced disease symptoms as well as decreased IL-12 and IFNgamma
      mRNAs in brain tissue. Immunohistochemical markers for myelination (MBP) and
      reactive astrogliosis (GFAP) confirmed recovery in mice treated with engineered
      Tregs compared to controls. Symptom-free mice were rechallenged with a second EAE
      inducing inoculum but remained healthy, demonstrating the sustained effect of
      engineered Tregs. CONCLUSION: CNS-targeting Tregs delivered i.n. localized to the
      CNS and efficiently suppressed ongoing inflammation leading to diminished disease
      symptoms.

PMID- 22647576
TI  - Cumulative estrogen exposure and prospective memory in older women.
AB  - This study looked at cumulative lifetime estrogen exposure, as estimated with a
      mathematical index (Index of Cumulative Estrogen Exposure (ICEE)) that included
      variables (length of time on estrogen therapy, age at menarche and menopause,
      postmenopausal body mass index, time since menopause, nulliparity and duration of
      breastfeeding) known to influence estrogen levels across the life span, and
      performance on prospective and retrospective memory measures in a group of 50
      postmenopausal women (mean age=69.3years) who, if they were current or former
      users of estrogen therapy, had started therapy within 5years of menopause. The
      ICEE was found to be a significant predictor of performance on the Prospective
      Memory task (F(1)=4.21, p=.046, eta(p)(2)=.084). No significant relationship was
      noted between the ICEE and performance on measures of retrospective memory. The
      results suggest that the level of cumulative lifetime exposure to estrogen a
      woman has influences her prospective memory performance later in life and that
      the influence of reproductive and biological markers of endogenous estrogen
      exposure are relevant factors to consider when studying the effect of estrogen
      therapy on cognitive functioning in postmenopausal women. In addition, the
      finding that performance on a measure of prospective memory, but not performance
      on measures of retrospective memory, was associated with the ICEE adds further
      support to the theory that the frontal cortex may be especially sensitive to
      estrogen.

PMID- 22647577
TI  - Hyperactivity induced by the dopamine D2/D3 receptor agonist quinpirole is
      attenuated by inhibitors of endocannabinoid degradation in mice.
AB  - The present study was designed to investigate the effect of pharmacological
      inhibition of endocannabinoid degradation on behavioural actions of the dopamine
      D2/D3 receptor agonist quinpirole in male C57Bl/6J mice. In addition, we studied
      the effects of endocannabinoid degradation inhibition on both cocaine-induced
      psychomotor activation and behavioural sensitization. We analysed the effects of
      inhibition of the two main endocannabinoid degradation enzymes: fatty acid amide
      hydrolase (FAAH), using inhibitor URB597 (1 mg/kg); monoacylglycerol lipase
      (MAGL), using inhibitor URB602 (10 mg/kg). Administration of quinpirole (1 mg/kg)
      caused a temporal biphasic response characterized by a first phase of immobility
      (0-50 min), followed by enhanced locomotion (next 70 min) that was associated
      with the introduction of stereotyped behaviours (stereotyped jumping and
      rearing). Pretreatment with both endocannabinoid degradation inhibitors did not
      affect the hypoactivity actions of quinpirole. However, this pretreatment
      resulted in a marked decrease in quinpirole-induced locomotion and stereotyped
      behaviours. Administration of FAAH or MAGL inhibitors did not attenuate the acute
      effects of cocaine. Furthermore, these inhibitors did not impair the acquisition
      of cocaine-induced behavioural sensitization or the expression of cocaine-induced
      conditioned locomotion. Only MAGL inhibition attenuated the expression of an
      already acquired cocaine-induced behavioural sensitization. These results suggest
      that pharmacological inhibition of endocannabinoid degradation might exert a
      negative feedback on D2/D3 receptor-mediated hyperactivity. This finding might be
      relevant for therapeutic approaches for either psychomotor disorders (dyskinesia,
      corea) or disorganized behaviours associated with dopamine-mediated
      hyperactivity.

PMID- 22647579
TI  - Profile: association for cancer immunotherapy (CIMT).

PMID- 22647578
TI  - Glucocorticoid sensitizers Bag1 and Ppid are regulated by adolescent stress in a
      sex-dependent manner.
AB  - Early life stress precipitates dysregulation of the hypothalamic-pituitary
      adrenal (HPA) axis and this effect is most pronounced in females. The mechanisms
      that mediate female sensitivity to stress-induced HPA axis dysregulation are
      unknown. The purpose of this study was to determine whether sex moderates the
      effects of chronic adolescent stress on glucocorticoid receptor (GR)
      translocation and moderators of the GR system. Female adolescent rats with a
      history of chronic stress exposure demonstrated a delayed resolution of the
      plasma corticosterone response to an acute stressor and this delay was
      accompanied by attenuated GR translocation compared to control adolescent
      females. The chronic stress-induced phenotype in females was similar to the
      baseline phenotype in male adolescent rats. Conversely, the expression patterns
      of GR moderators/co-chaperones became more sexually dimorphic following chronic
      stress, suggesting divergent function of the GR system between male and female
      adolescent rats. Gene expression of Ppid, a positive regulator of the GR, was
      predicted by plasma estradiol and 34% lower in control adolescent females than
      males, indicating that sex steroids may play a role in the sexually dimorphic
      response. After chronic adolescent stress, females displayed elevated hippocampal
      expression of Bag1 and Ppid genes that was not observed in males. Overall, the GR
      output to an acute stressor, illustrated by transcription of Nr3c1 (encoding the
      GR), Bag1, Fkbp5, Ppid, and Src1, was significantly upregulated and differed in a
      sex-specific and chronic stress-dependent manner. This study provides new
      evidence for sex differences during development and adaptation of the
      glucocorticoid receptor chaperone system.

PMID- 22647582
TI  - Expression of prolactin receptors in normal canine mammary tissue, canine mammary
      adenomas and mammary adenocarcinomas.
AB  - BACKGROUND: Mammary tumors represent the most common neoplastic disease in female
      dogs. Recently, the promoting role of prolactin (PRL) in the development of human
      breast carcinoma has been shown. Possible proliferative, anti-apoptotic,
      migratory and angiogenic effects of PRL on human mammary cancer cells in vitro
      and in vivo were suggested. The effects of PRL are mediated by its receptor, and
      alterations in receptor expression are likely to play a role in tumor
      development. Currently, not much data is available about prolactin receptor
      (PRLR) expression in canine mammary tumors. To set the basis for investigations
      on the role of PRL in mammary tumorigenesis in this species, prolactin receptor
      expression was evaluated by semi-quantitative real time PCR and
      immunohistochemistry on 10 formalin-fixed, paraffin-embedded samples each of
      canine non-neoplastic mammary tissue, mammary adenomas and adenocarcinomas.
      RESULTS: The highest PRLR expression levels were found in normal mammary tissue,
      while adenomas, and to an even higher degree adenocarcinomas, showed a
      significant decrease in prolactin receptor expression. Compared to normal tissue,
      PRLR mRNA was reduced 2.4 fold (p = 0.0261) in adenomas and 4.8 fold (p = 0.008)
      in adenocarcinomas. PRLR mRNA expression was significantly lower in malignant
      than in benign lesions (p = 0.0165). Immunohistochemistry demonstrated PRLR
      expression in all three tissue types with signals mostly limited to epithelial
      cells. CONCLUSIONS: Malignant transformation of mammary tissue was associated
      with a decline in prolactin receptor expression. Further studies are warranted to
      address the functional significance of this finding.

PMID- 22647583
TI  - Distinctive clinicopathological features of 2 large families with amyotrophic
      lateral sclerosis having L106V mutation in SOD1 gene.
AB  - A clinicopathological study of 2 families with familial amyotrophic lateral
      sclerosis was previously reported [1]. The present study continues to investigate
      these families, with detailed clinical, genetic, and neuropathological studies
      performed on 24 patients, including 5 autopsy cases of the families. A point
      mutation at codon 106 (L106V) in the copper/zinc superoxide dismutase-1 (SOD1)
      gene was identified in the families. Average age at onset was 52.0 +/- 9.4 years,
      and initial symptoms were weakness and atrophy in the distal muscles of the lower
      extremities in most patients. Half of the patients showed neurogenic bladder
      (overactive bladder) and sensory impairment. The neurophysiological study showed
      peripheral/central conduction delay. Neuropathological examination revealed
      severe motor neuron loss with many bizarre reactive astrocytes in the spinal
      anterior horn. SOD1-immunopositive Lewy body-like hyaline inclusions and
      aggregation of neurofilaments were observed in the surviving anterior horn cells.
      Degeneration of the corticospinal tract was relatively minor. In addition, slight
      but diffuse gliosis was identified in the hypothalamus and medial nucleus of
      thalamus. Neurogenic bladder, sensory impairment, and degeneration of the
      hypothalamus and thalamus might be specific features in patients with familial
      amyotrophic lateral sclerosis with L106V mutation in the SOD1 gene.

PMID- 22647584
TI  - Is peripheral neuron degeneration involved in multiple system atrophy? A clinical
      and electrophysiological study.
AB  - Lower motor neuron lesions are not among the characteristic features of multiple
      system atrophy (MSA), although electromyography (EMG) and autopsy studies
      revealed peripheral neuron abnormalities in some cases of MSA. The aim of the
      study was to evaluate subclinical involvement of the peripheral neuron in MSA
      using EMG and electroneurography (ENG). MATERIAL: 48 patients with clinically
      probable MSA (mean age 60.6 years; 67% males) were included in the study and
      divided into subgroups, with predominant cerebellar (MSA-C) and parkinsonian
      signs (MSA-P). METHODS: ENG in ulnar, peroneal and sural nerves and EMG of the
      first interosseus dorsal and tibial anterior muscles were performed. RESULTS:
      Abnormal ENG in one nerve was recorded in 20.8% of patients, and in two nerves in
      another 20.8% of patients. The most frequent and significant findings were
      decreased compound motor action potential amplitudes in the ulnar nerve in the
      overall MSA group as well as in the MSA-P type as compared to controls.
      Abnormalities suggesting reinnervation was observed in 43 of 96 examined muscles
      (44.7%). In individual cases, neurogenic features were recorded in one muscle in
      31.2% of patients and in two muscles in 29.1% of patients. CONCLUSIONS:
      Subclinical axonopathy in MSA is not frequent and is more pronounced in MSA with
      predominant parkinsonian signs. In MSA, neurogenic EMG abnormalities in muscles
      are more frequent than peripheral nerve lesions and as evidenced by increased
      motor unit potential amplitudes, could be considered a sign of anterior horn cell
      involvement and a hallmark of the "continuum" of neurodegeneration in MSA.

PMID- 22647585
TI  - Viability of autoantibody-targets: how to tackle pathogenetic heterogeneity as an
      obstacle for treatment of multiple sclerosis.
AB  - The growing complexity number of multiple sclerosis (MS) therapy emphasizes the
      need for an individualized approach, tailoring therapy to the needs of the
      individual patient. There is evidence supporting the immunopathological
      heterogeneity of MS, based on the analysis of biopsy and autopsy tissues. In
      clinical practice it is impossible to differentiate between the pathological
      subtypes of MS, because blood or CSF markers of pathological heterogeneity are
      lacking. Identification of such markers would be important, because "tailored
      therapy" and "biomarkers for patient stratification" may be considered as two
      sides of the same coin. In this article, we discuss the emerging role of
      autoantibodies as potential biomarkers, focusing on myelin oligodendrocyte
      glycoprotein (MOG) as one of the best characterized autoantigens in MS. In
      addition, we discuss several strategies for the identification of novel candidate
      autoantigens.

PMID- 22647586
TI  - The effects of heat stress on physical functioning in persons with multiple
      sclerosis.
AB  - Heat sensitivity is a well-recognised feature in multiple sclerosis (MS).
      However, little is known about how heat affects physical performance in persons
      with MS. The objective of the study was to evaluate the effects of short-term
      heat stress on physical functioning in persons with MS. Twenty-three heat
      sensitive MS subjects and 19 healthy controls participated. Moderate heat
      exposure took place in a dry Finnish sauna. Measures of upper and lower extremity
      function, static and dynamic balance, and walking capacity were applied. Core
      body temperature was measured by a telemetric physiological monitoring system.
      Assessments were conducted before, immediately, 1 hour, and 1 day after the heat
      exposure. Subjects with MS showed a significantly (P=0.002) higher core body
      temperature than the controls following the heat stress. Performances in walking
      (P<0.001), chair rise (P=0.005) and functional reach (P=0.04) were poorer in MS
      subjects than in controls immediately after the heat. No prolonged heat effects
      were observed. An increase in ambient temperature causes a higher core body
      temperature rise in MS subjects than in healthy controls. This rise in
      temperature is associated with acute, but not prolonged detrimental effects on
      physical functioning.

PMID- 22647587
TI  - A case control study of women with Parkinson's disease and their fertility
      characteristics.
AB  - BACKGROUND: Parkinson disease (PD) is less common in women and studies have shown
      that oestrogen is protective to dopaminergic neurons in primate models. The
      findings in clinical and epidemiological studies have not clearly established
      this observation. This study was undertaken to evaluate associations of
      reproductive characteristics in a population with higher fertility and risk of PD
      among women. METHODS: Trained interviewers used structured interviews to obtain
      information about demographic characteristics and reproductive history from women
      subjects with PD. An equal number of healthy age matched female controls were
      also studied to compare their reproductive characteristics with women with PD.
      RESULTS: We recruited 81 consecutive women with PD and age matched healthy women
      controls. Mean age at interview was 55.89 +/- 10.07 years for women with PD,
      55.05 +/- 10.53 years for controls. Significant positive correlation was observed
      with cumulative length of pregnancy (r=0.32; p=0.003), age at menopause (r=0.55;
      p=0.001) and length of fertile life with age of onset of PD (r=0.27; p=0.02).
      Gravidity (r=0.26; p=0.02) and parity (r=0.35; p=0.001) also correlated
      positively with age at onset. CONCLUSION: The onset of PD is delayed in women
      with higher number of pregnancies, longer fertile life and longer cumulative
      length of pregnancies. This could also explain the epidemiological observations
      of lower incidence of PD in women and the protective role of estrogens.

PMID- 22647588
TI  - Key harm reduction interventions and their impact on the reduction of risky
      behavior and HIV incidence among people who inject drugs in low-income and middle
      income countries.
AB  - PURPOSE OF REVIEW: HIV infection rates continue to rise among people who inject
      drugs (PWID) in many lower- and middle-income countries (LMICs). Although
      progress is being made in prevention and care for PWID in some settings, coverage
      of essential services remains low. This article reviews the evidence for the
      benefits of scaling up key interventions as a combination prevention and
      treatment package for PWID. RECENT FINDINGS: WHO defined a comprehensive package
      of nine interventions for PWID, of which the following four have evidence for
      effectiveness in reducing HIV incidence: needle and syringe programs (NSP),
      medication-assisted therapy (MAT), antiretroviral therapy (ART), and HIV
      counseling and testing (HCT). Coverage of these interventions among PWID in LMICs
      varies from low (<=20%) to medium (>20-60%). At least a 60% coverage is likely to
      be required to reduce HIV incidence. Evidence from LMIC contexts suggests that
      NSP and MAT can reduce high-risk injecting behavior, HCT can reduce risky sexual
      behavior and ART can plausibly have preventive benefit among PWID for onward
      parenteral transmission with clearer evidence that antiretroviral therapy (ARV)
      can prevent onward sexual transmission. Modeling analysis suggests that compared
      with current low coverage, a scale-up of these four interventions in combination
      would be a beneficial and cost-effective approach. SUMMARY: The continuation of
      significant HIV incidence among PWID in LMIC settings is avoidable with the
      implementation of immediate scale-up of key harm reduction and ARV treatment
      interventions. Policymakers should address the structural and resource allocation
      barriers to allow this scale-up to occur.

PMID- 22647589
TI  - Current advances in pharmacovigilance in the USA and Europe:  meeting the
      challenges of safety monitoring in HIV.
AB  - PURPOSE OF REVIEW: The success of antiretroviral therapy in HIV disease comes
      currently with the realization that patients are committed to life-long
      treatment, which raises the possibility of long-term toxicity. Such long-term
      side effects may not be identified in initial clinical trials requiring,
      therefore, a different approach to monitoring patients over time - a
      pharmacovigilance approach. RECENT FINDINGS: Several key issues in long-term
      management of HIV infection have been addressed by a pharmacovigilance approach -
      including unusual and rare side effects and elucidation of emerging toxicities
      such as cardiovascular, bone and renal disease. Recent changes in legislation in
      the USA and Europe are aimed to strengthen pharmacovigilance in developed
      countries. SUMMARY: HIV infection and its treatment provide an important example
      of the role of pharmacovigilance. As clinical trials can rarely address the
      question of long-term tolerability, effective pharmacovigilance programs are and
      will remain essential.

PMID- 22647590
TI  - Maternal obesity and venous thromboembolism.
AB  - The incidence of obesity in pregnancy has increased rapidly in the last decade.
      Obesity is a risk factor for venous thromboembolism outside of pregnancy and
      previous studies of maternal death in the UK have identified obesity as a risk
      factor in pregnancy. As a result the Royal College of Obstetricians and
      Gynaecologists have targeted obesity as a risk factor in evaluation of the need
      for thromboprophylaxis in pregnancy. This article highlights the evidence that
      obesity increases the risk of venous thromboembolism in pregnancy and the
      puerperium, discusses thromboprophylaxis and appropriate dosing in obese
      parturients and details the anaesthetic implications of the 2009 Royal College of
      Obstetricians and Gynaecologists' guidelines. More clinical studies are required
      to clarify the appropriate dose of low-molecular-weight heparin in an obese
      parturient.

PMID- 22647591
TI  - Antibiotic timing at caesarean section.

PMID- 22647592
TI  - Postpartum hemorrhage treated with a massive transfusion protocol at a tertiary
      obstetric center: a retrospective study.
AB  - BACKGROUND: A massive transfusion protocol may offer major advantages for
      management of postpartum hemorrhage. The etiology of postpartum hemorrhage,
      transfusion outcomes and laboratory indices in obstetric cases requiring the
      massive transfusion protocol were retrospectively evaluated in a tertiary
      obstetric center. METHODS: We reviewed medical records of obstetric patients
      requiring the massive transfusion protocol over a 31-month period. Demographic,
      obstetric, transfusion, laboratory data and adverse maternal outcomes were
      abstracted. RESULTS: Massive transfusion protocol activation occurred in 31
      patients (0.26% of deliveries): 19 patients (61%) had cesarean delivery, 10
      patients (32%) had vaginal delivery, and 2 patients (7%) had dilation and
      evacuation. Twenty-six patients (84%) were transfused with blood products from
      the massive transfusion protocol. The protocol was activated within 2h of
      delivery for 17 patients (58%). Median [IQR] total estimated blood loss value was
      2842 [800-8000]mL. Median [IQR] number of units of red blood cells, plasma and
      platelets from the massive transfusion protocol were: 3 [1.75-7], 3 [1.5-5.5],
      and 1 [0-2.5] units, respectively. Mean (SD) post-resuscitation hematologic
      indices were: hemoglobin 10.3 (2.4)g/dL, platelet count 126 (44)*10(9)/L, and
      fibrinogen 325 (125)mg/dL. The incidence of intensive care admission and
      peripartum hysterectomy was 61% and 19%, respectively. CONCLUSIONS: Our massive
      transfusion protocol provides early access to red blood cells, plasma and
      platelets for patients experiencing unanticipated or severe postpartum
      hemorrhage. Favorable hematologic indices were observed post resuscitation.
      Future outcomes-based studies are needed to compare massive transfusion protocol
      and non-protocol based transfusion strategies for the management of hemorrhage.

PMID- 22647593
TI  - High prevalence of nasal carriage of beta-lactamase-negative ampicillin-resistant
      Haemophilus influenzae in healthy children in Korea.
AB  - This study investigated the carriage of antimicrobial resistant Haemophilus
      influenzae in 582 healthy children attending kindergarten or elementary school at
      four intervals over a 9-month period in Seoul, Korea. Diverse colonization
      patterns and a lower level of long-term persistent carriage by H. influenzae
      status were evident in this study. Colonizing H. influenzae isolates showed a
      high rate of resistance to beta-lactams including ampicillin (51.9%), cefaclor
      (52.1%), and amoxicillin/clavulanate (16.3%). Based on the ampicillin resistance
      mechanism, H. influenzae isolates were categorized as beta-lactamase-negative,
      ampicillin-susceptible (BLNAS) (48.1%), beta-lactamase-positive, ampicillin
      resistant (BLPAR) (22.6%), beta-lactamase-negative, ampicillin-resistant (BLNAR)
      (22.8%), and beta-lactamase-positive, amoxicillin/clavulanate-resistant (BLPACR)
      strains (6.5%). This study provides the first evidence of a high prevalence
      (22.8%) of BLNAR strains of H. influenzae nasal carriage in healthy children
      attending kindergarten or the first 2 years of elementary school in Korea. The
      high carriage of these resistant strains in overcrowded urban settings may create
      reservoirs for development of H. influenzae-resistant strains.

PMID- 22647594
TI  - A gallery of the key characters to ease identification of Dermanyssus gallinae
      (Acari: Gamasida: Dermanyssidae) and allow differentiation from Ornithonyssus
      sylviarum (Acari: Gamasida: Macronyssidae).
AB  - BACKGROUND: Dermanyssus gallinae (poultry red mite) is a major threat for the
      poultry industry and is of significant interest for public health. Identification
      of D. gallinae can be difficult for scientists not familiar with mite morphology
      and terminology especially when trying to use identification keys. Moreover, this
      species may easily be confused with another dermanyssoid mite, Ornithonyssus
      sylviarum (northern fowl mite), which often shares the same hosts and
      environment. METHODS: Specimens of D. gallinae were collected at poultry farms in
      the Puglia and performed for light and scanning electron microscopy observations,
      identification and micrographs. Moreover specimens of O. sylviarum were collected
      separately macerated and mounted on slides for light microscopy observations,
      identification and pictures. RESULTS: The micrographs used in this study, based
      on LM and SEM observations, highlight the following important identifying
      characters of D. gallinae: the prominent shoulders of the dorsal shield and the
      jagged edges of the shield reticulations, the position of setae j1, s1 and the
      epigynal pores, and the presence on tibia IV pl of one seta. Additional
      micrographs highlighting the shape of the dorsal (abruptly narrowed posteriorly)
      and epigynal (narrowly rounded posteriorly) shields and the chelicera (elongate,
      with distinct digits) of O. sylviarum enable its differentiation from D.gallinae.
      CONCLUSION: The photographic support provided here (both LM and SEM pictures) can
      be considered a practical tool for scientists who are not well acquainted with
      the morphology of D.gallinae, and who are involved with classical and molecular
      systematics, veterinary and human health aspects of poultry red mites.

PMID- 22647596
TI  - Acute and chronic pain in calves after different methods of rubber-ring
      castration.
AB  - The goal of the present study was to evaluate the effect of different methods of
      rubber-ring castration on acute and chronic pain in calves. Sixty-three 4-6 week
      old calves were randomly and sequentially allocated to one of five groups: Group
      RR (traditional rubber ring castration); group BRR (combination of one rubber
      ring with Burdizzo); group Rcut (one rubber ring applied with the scrotal tissue
      and rubber ring removed on day 9); group 3RR (three rubber rings placed one above
      the other around the scrotal neck); and group CO (controls; sham-castrated). All
      calves received 0.2 mL/kg bodyweight lidocaine 2%, injected into the spermatic
      cords and around the scrotal neck 15 min before castration. The presence of acute
      and chronic pain was assessed using plasma cortisol concentrations, response to
      palpation of scrotal area, time from castration until complete wound healing, and
      behavioural signs. Calves of group 3RR showed severe swelling and inflammation,
      and licking of the scrotal area occurred significantly more often than in groups
      Rcut and CO. Technique 3RR was discontinued for welfare reasons before the end of
      the study. All castration groups had significantly more pain upon palpation than
      calves of group CO, but palpation elicited markedly less pain in group Rcut than
      in the other castration groups. The most rapid healing time and shortest duration
      of chronic pain after castration was achieved in group Rcut. For welfare reasons,
      the Rcut technique should be considered as a valuable alternative to traditional
      rubber ring castration of calves at 4-6 weeks of age.

PMID- 22647595
TI  - Mentoring support from clinical supervisors: mentor motives and associations with
      counselor work-to-nonwork conflict.
AB  - Based on mentoring theory, social exchange theory, and theories of stress and
      coping, this study examined antecedents and consequences of the provision of
      mentoring support by clinical supervisors. Of particular interest is how the
      provision of mentoring support is further linked to counselor's experience of
      work-to-nonwork conflict. Survey data were collected in person in 2008 from 418
      matched clinical supervisor-counselor dyads who worked in substance use disorder
      treatment programs across the U.S. Path analysis showed that clinical
      supervisors' evaluation of relational costs, relational benefits, and overall
      relationship quality with a particular counselor was related to the counselor's
      perception of the amount of mentoring support provided. In turn, perceived
      mentoring support was negatively related to both strain-based and time-based work
      to-nonwork conflict among counselors. These findings suggest that counselors and
      clinical supervisors should be encouraged to build positive social exchanges to
      help reduce perceptions of counselor work-to-nonwork conflict.

PMID- 22647597
TI  - From memory to antifungal vaccine design.
AB  - Fungal infections and related diseases have a high morbidity and mortality rate.
      Human antifungal vaccines are therefore of great interest, however, their
      development is challenging. Major hurdles include fungal species-specific
      differences in pathogenic mechanisms and strategies to escape immune
      surveillance, as well as the fact that individuals susceptible to infection do
      not necessarily share the same risk factors. Progress in antifungal vaccines
      demands the integration of immunology with systems biology, immunogenetics and
      bioinformatics in the arena of both fungal and host biology. Bridging the fields
      of basic immunology and vaccine research is needed to create individualized host
      immune profiles that will direct the rational development of customized adjuvants
      and vaccines with a predicted efficacy in each target population.

PMID- 22647598
TI  - Myotubularin-related protein (MTMR) 9 determines the enzymatic activity,
      substrate specificity, and role in autophagy of MTMR8.
AB  - The myotubularins are a large family of inositol polyphosphate 3-phosphatases
      that, despite having common substrates, subsume unique functions in cells that
      are disparate. The myotubularin family consists of 16 different proteins, 9
      members of which possess catalytic activity, dephosphorylating
      phosphatidylinositol 3-phosphate [PtdIns(3)P] and phosphatidylinositol 3,5
      bisphosphate [PtdIns(3,5)P(2)] at the D-3 position. Seven members are inactive
      because they lack the conserved cysteine residue in the CX(5)R motif required for
      activity. We studied a subfamily of homologous myotubularins, including
      myotubularin-related protein 6 (MTMR6), MTMR7, and MTMR8, all of which dimerize
      with the catalytically inactive MTMR9. Complex formation between the active
      myotubularins and MTMR9 increases their catalytic activity and alters their
      substrate specificity, wherein the MTMR6/R9 complex prefers PtdIns(3,5)P(2) as
      substrate; the MTMR8/R9 complex prefers PtdIns(3)P. MTMR9 increased the enzymatic
      activity of MTMR6 toward PtdIns(3,5)P(2) by over 30-fold, and enhanced the
      activity toward PtdIns(3)P by only 2-fold. In contrast, MTMR9 increased the
      activity of MTMR8 by 1.4-fold and 4-fold toward PtdIns(3,5)P(2) and PtdIns(3)P,
      respectively. In cells, the MTMR6/R9 complex significantly increases the cellular
      levels of PtdIns(5)P, the product of PI(3,5)P(2) dephosphorylation, whereas the
      MTMR8/R9 complex reduces cellular PtdIns(3)P levels. Consequentially, the
      MTMR6/R9 complex serves to inhibit stress-induced apoptosis and the MTMR8/R9
      complex inhibits autophagy.

PMID- 22647599
TI  - Functional organization of the insula and inner perisylvian regions.
AB  - In the last few years, the insula has been the focus of many brain-imaging
      studies, mostly devoted to clarify its role in emotions and social communication.
      Physiological data, however, on which one may ground these correlative findings
      are almost totally lacking. Here, we investigated the functional properties of
      the insular cortex in behaving monkeys using intracortical microstimulation.
      Behavioral responses and heart rate changes were recorded. The results showed
      that the insula is functionally formed by two main subdivisions: (i) a
      sensorimotor field occupying the caudal-dorsal portion of the insula and
      appearing as an extension of the parietal lobe; and (ii) a mosaic of orofacial
      motor programs located in the anterior and centroventral insula sector. These
      programs show a progressive shift from dorsally located nonemotional motor
      programs (ingestive activity) to ventral ones laden with emotional and
      communicative content. The relationship between ingestive and other behaviors is
      discussed in an evolutionary perspective.

PMID- 22647600
TI  - Akt1 and Akt2 protein kinases differentially contribute to macrophage
      polarization.
AB  - Activated macrophages are described as classically activated or M1 type and
      alternatively activated or M2 type, depending on their response to
      proinflammatory stimuli and the expression of genetic markers including iNOS,
      arginase1, Ym1, and Fizz1. Here we report that Akt kinases differentially
      contribute to macrophage polarization, with Akt1 ablation giving rise to an M1
      and Akt2 ablation resulting in an M2 phenotype. Accordingly, Akt2(-/-) mice were
      more resistant to LPS-induced endotoxin shock and to dextran sulfate sodium (DSS)
      induced colitis than wild-type mice, whereas Akt1(-/-) mice were more sensitive.
      Cell depletion and reconstitution experiments in a DSS-induced colitis model
      confirmed that the effect was macrophage-dependent. Gene-silencing studies showed
      that the M2 phenotype of Akt2(-/-) macrophages was cell autonomous. The microRNA
      miR-155, whose expression was repressed in naive and in LPS-stimulated Akt2(-/-)
      macrophages, and its target C/EBPbeta appear to play a key role in this process.
      C/EBPbeta, a hallmark of M2 macrophages that regulates Arg1, was up-regulated
      upon Akt2 ablation or silencing. Overexpression or silencing of miR-155 confirmed
      its central role in Akt isoform-dependent M1/M2 polarization of macrophages.

PMID- 22647601
TI  - Peroxisome proliferator-activated receptor (PPAR)alpha and -gamma regulate
      IFNgamma and IL-17A production by human T cells in a sex-specific way.
AB  - Women develop certain autoimmune diseases more often than men. It has been
      hypothesized that this may relate to the development of more robust T-helper
      (Th)1 responses in women. To test whether women exhibit a Th1 bias, we isolated
      naive cluster of differentiation (CD)4(+) T cells from peripheral blood of
      healthy women and men and measured the proliferation and cytokine production by
      these cells in response to submaximal amounts of anti-CD3 and anti-CD28. We
      observed that CD4(+) T cells from women produced higher levels of IFNgamma as
      well as tended to proliferate more than male CD4(+) T cells. Intriguingly, male
      CD4(+) T cells instead had a predilection toward IL-17A production. This sex
      dichotomy in Th cytokine production was found to be even more striking in the
      Swiss/Jackson Laboratory (SJL) mouse. Studies in mice and humans indicated that
      the sexual dimorphism in Th1 and Th17 cytokine production was dependent on the
      androgen status and the T-cell expression of peroxisome proliferator activated
      receptor (PPAR)alpha and PPARgamma. Androgens increased PPARalpha and decreased
      PPARgamma expression by human CD4(+) T cells. PPARalpha siRNA-mediated knockdown
      had the effect of increasing IFNgamma by male CD4(+) T cells, while transfection
      of CD4(+) T cells with PPARgamma siRNAs increased IL-17A production uniquely by
      female T cells. Together, our observations indicate that human T cells exhibit a
      sex difference in the production of IFNgamma and IL-17A that may be driven by
      expressions of PPARalpha and PPARgamma.

PMID- 22647602
TI  - Loss of P-type ATPase ATP13A2/PARK9 function induces general lysosomal deficiency
      and leads to Parkinson disease neurodegeneration.
AB  - Parkinson disease (PD) is a progressive neurodegenerative disorder pathologically
      characterized by the loss of dopaminergic neurons from the substantia nigra pars
      compacta and the presence, in affected brain regions, of protein inclusions named
      Lewy bodies (LBs). The ATP13A2 gene (locus PARK9) encodes the protein ATP13A2, a
      lysosomal type 5 P-type ATPase that is linked to autosomal recessive familial
      parkinsonism. The physiological function of ATP13A2, and hence its role in PD,
      remains to be elucidated. Here, we show that PD-linked mutations in ATP13A2 lead
      to several lysosomal alterations in ATP13A2 PD patient-derived fibroblasts,
      including impaired lysosomal acidification, decreased proteolytic processing of
      lysosomal enzymes, reduced degradation of lysosomal substrates, and diminished
      lysosomal-mediated clearance of autophagosomes. Similar alterations are observed
      in stable ATP13A2-knockdown dopaminergic cell lines, which are associated with
      cell death. Restoration of ATP13A2 levels in ATP13A2-mutant/depleted cells
      restores lysosomal function and attenuates cell death. Relevant to PD, ATP13A2
      levels are decreased in dopaminergic nigral neurons from patients with PD, in
      which ATP13A2 mostly accumulates within Lewy bodies. Our results unravel an
      instrumental role of ATP13A2 deficiency on lysosomal function and cell viability
      and demonstrate the feasibility and therapeutic potential of modulating ATP13A2
      levels in the context of PD.

PMID- 22647603
TI  - Sources of energy for gating by neurotransmitters in acetylcholine receptor
      channels.
AB  - Nicotinic acetylcholine receptors (AChRs) mediate signaling in the central and
      peripheral nervous systems. The AChR gating conformational change is powered by a
      low- to high-affinity change for neurotransmitters at two transmitter binding
      sites. We estimated (from single-channel currents) the components of energy for
      gating arising from binding site aromatic residues in the alpha-subunit. All
      mutations reduced the energy (TyrC1>>TrpB~TyrC2>TyrA), with TyrC1 providing ~40%
      of the total. Considered one at a time, the fractional energy contributions from
      the aromatic rings were TrpB ~35%, TyrC1 ~28%, TyrC2 ~28%, and TyrA ~10%.
      Together, TrpB, TyrC1, and TyrC2 comprise an "aromatic triad" that provides much
      of the total energy from the transmitter for gating. Analysis of mutant pairs
      suggests that the energy contributions from some residues are nearly independent.
      Mutations of TyrC1 cause particularly large energy reductions because they remove
      two favorable and approximately equal interactions between the aromatic ring and
      the quaternary amine of the agonist and between the hydroxyl and alphaLysbeta7.

PMID- 22647604
TI  - Infection of Epstein-Barr virus in a gastric carcinoma cell line induces
      anchorage independence and global changes in gene expression.
AB  - Latent infection of EBV is linked to the development of multiple cancers that
      have distinct patterns of expression of viral proteins and microRNAs (miRNAs). In
      this study, we show that in vitro infection of a gastric epithelial cell line
      with EBV alters growth properties and induces growth in soft agar. The infected
      cells have high levels of expression of a large cluster of viral miRNAs, [the
      BamHI A rightward transcript (BART) miRNAs] and limited viral protein expression.
      Expression profile microarray analysis of this cell line revealed a large number
      of changes in cellular expression, with decreased expression of many genes.
      Inhibition of the trace-expressed levels of the viral oncoprotein, latent
      membrane protein 1, did not affect growth or alter the pattern of cellular
      expression. The expression changes are highly enriched for genes involved in cell
      motility and transformation pathways, suggesting these changes are important for
      the altered growth phenotype. Importantly, the transcripts decreased by
      microarray are significantly enriched in both experimentally and
      bioinformatically predicted BART miRNA targets. The absence of viral protein
      expression and the enrichment for viral miRNA targets in the modulated cell genes
      suggest that the BART miRNAs are major contributors to the transformed growth
      properties of the EBV-infected cells. The ability to affect cell growth through
      miRNA expression without viral protein expression would be a major factor in the
      development of cancer in individuals with functional immune systems.

PMID- 22647606
TI  - Uranium isotope compositions of the basaltic angrite meteorites and the
      chronological implications for the early Solar System.
AB  - Events occurring within the first 10 million years of the Solar System's
      approximately 4.5 billion-year history, such as formation of the first solids,
      accretion, and differentiation of protoplanetary bodies, have determined the
      evolutionary course of our Solar System and the planetary bodies within it. The
      application of high-resolution chronometers based on short-lived radionuclides is
      critical to our understanding of the temporal sequence of these critical events.
      However, to map the relative ages from such chronometers onto the absolute time
      scale, they must be "anchored" to absolute ages of appropriate meteoritic
      materials using the high-precision lead-lead (Pb-Pb) chronometer. Previously
      reported Pb-Pb dates of the basaltic angrite meteorites, some of which have been
      used extensively as time anchors, assumed a constant (238)U/(235)U ratio (=
      137.88). In this work, we report measurements of (238)U/(235)U ratios in several
      angrites that are distinct from the previously assumed value, resulting in
      corrections to the Pb-Pb ages of >= 1 million years. There is no resolvable
      variation in the (238)U/(235)U ratio among the angrite bulk samples or mineral
      separates, suggesting homogeneity in the U isotopic composition of the angrite
      parent body. Based on these measurements, we recalculated the Pb-Pb age for the
      commonly used anchor, the D'Orbigny angrite, to be 4563.37 +/- 0.25 Ma. An
      adjustment to the Pb-Pb age of a time anchor (such as D'Orbigny) requires a
      corresponding correction to the "model ages" of all materials dated using that
      anchor and a short-lived chronometer. This, in turn, has consequences for
      accurately defining the absolute timeline of early Solar System events.

PMID- 22647605
TI  - Azidoblebbistatin, a photoreactive myosin inhibitor.
AB  - Photoreactive compounds are important tools in life sciences that allow precisely
      timed covalent crosslinking of ligands and targets. Using a unique technique we
      have synthesized azidoblebbistatin, which is a derivative of blebbistatin, the
      most widely used myosin inhibitor. Without UV irradiation azidoblebbistatin
      exhibits identical inhibitory properties to those of blebbistatin. Using UV
      irradiation, azidoblebbistatin can be covalently crosslinked to myosin, which
      greatly enhances its in vitro and in vivo effectiveness. Photo-crosslinking also
      eliminates limitations associated with the relatively low myosin affinity and
      water solubility of blebbistatin. The wavelength used for photo-crosslinking is
      not toxic for cells and tissues, which confers a great advantage in in vivo
      tests. Because the crosslink results in an irreversible association of the
      inhibitor to myosin and the irradiation eliminates the residual activity of
      unbound inhibitor molecules, azidoblebbistatin has a great potential to become a
      highly effective tool in both structural studies of actomyosin contractility and
      the investigation of cellular and physiological functions of myosin II. We used
      azidoblebbistatin to identify previously unknown low-affinity targets of the
      inhibitor (EC(50) >= 50 MUM) in Dictyostelium discoideum, while the strongest
      interactant was found to be myosin II (EC(50) = 5 MUM). Our results demonstrate
      that azidoblebbistatin, and potentially other azidated drugs, can become highly
      useful tools for the identification of strong- and weak-binding cellular targets
      and the determination of the apparent binding affinities in in vivo conditions.

PMID- 22647607
TI  - From antiferromagnetic insulator to correlated metal in pressurized and doped
      LaMnPO.
AB  - Widespread adoption of superconducting technologies awaits the discovery of new
      materials with enhanced properties, especially higher superconducting transition
      temperatures T(c). The unexpected discovery of high T(c) superconductivity in
      cuprates suggests that the highest T(c)s occur when pressure or doping transform
      the localized and moment-bearing electrons in antiferromagnetic insulators into
      itinerant carriers in a metal, where magnetism is preserved in the form of strong
      correlations. The absence of this transition in Fe-based superconductors may
      limit their T(c)s, but even larger T(c)s may be possible in their isostructural
      Mn analogs, which are antiferromagnetic insulators like the cuprates. It is
      generally believed that prohibitively large pressures would be required to
      suppress the effects of the strong Hund's rule coupling in these Mn-based
      compounds, collapsing the insulating gap and enabling superconductivity. Indeed,
      no Mn-based compounds are known to be superconductors. The electronic structure
      calculations and X-ray diffraction measurements presented here challenge these
      long held beliefs, finding that only modest pressures are required to transform
      LaMnPO, isostructural to superconducting host LaFeAsO, from an antiferromagnetic
      insulator to a metallic antiferromagnet, where the Mn moment vanishes in a second
      pressure-driven transition. Proximity to these charge and moment delocalization
      transitions in LaMnPO results in a highly correlated metallic state, the familiar
      breeding ground of superconductivity.

PMID- 22647608
TI  - Low-temperature, manganese oxide-based, thermochemical water splitting cycle.
AB  - Thermochemical cycles that split water into stoichiometric amounts of hydrogen
      and oxygen below 1,000  degrees C, and do not involve toxic or corrosive
      intermediates, are highly desirable because they can convert heat into chemical
      energy in the form of hydrogen. We report a manganese-based thermochemical cycle
      with a highest operating temperature of 850  degrees C that is completely
      recyclable and does not involve toxic or corrosive components. The thermochemical
      cycle utilizes redox reactions of Mn(II)/Mn(III) oxides. The shuttling of Na(+)
      into and out of the manganese oxides in the hydrogen and oxygen evolution steps,
      respectively, provides the key thermodynamic driving forces and allows for the
      cycle to be closed at temperatures below 1,000  degrees C. The production of
      hydrogen and oxygen is fully reproducible for at least five cycles.

PMID- 22647609
TI  - Nucleotide-dependent conformations of FtsZ dimers and force generation observed
      through molecular dynamics simulations.
AB  - The bacterial cytoskeletal protein FtsZ is a GTPase that is thought to provide
      mechanical constriction force via an unidentified mechanism. Purified FtsZ
      polymerizes into filaments with varying structures in vitro: while GTP-bound FtsZ
      assembles into straight or gently curved filaments, GDP-bound FtsZ forms highly
      curved filaments, prompting the hypothesis that a difference in the inherent
      curvature of FtsZ filaments provides mechanical force. However, no nucleotide
      dependent structural transition of FtsZ monomers has been observed to support
      this force generation model. Here, we present a series of all-atom molecular
      dynamics simulations probing the effects of nucleotide binding on the structure
      of an FtsZ dimer. We found that the FtsZ-dimer structure is dependent on
      nucleotide-binding state. While a GTP-bound FtsZ dimer retained a firm monomer
      monomer contact, a GDP-bound FtsZ dimer lost some of the monomer-monomer
      association, leading to a "hinge-opening" event that resulted in a more bent
      dimer, while leaving each monomer structure largely unaffected. We constructed
      models of FtsZ filaments and found that a GDP-FtsZ filament is much more curved
      than a GTP-FtsZ filament, with the degree of curvature matching prior
      experimental data. FtsZ dynamics were used to estimate the amount of force an
      FtsZ filament could exert when hydrolysis occurs (20-30 pN per monomer). This
      magnitude of force is sufficient to direct inward cell-wall growth during
      division, and to produce the observed degree of membrane pinching in liposomes.
      Taken together, our data provide molecular-scale insight on the origin of FtsZ
      based constriction force, and the mechanism underlying prokaryotic cell division.

PMID- 22647610
TI  - Strategy for enhanced transgenic strain development for embryonic conditional
      lethality in Anastrepha suspensa.
AB  - Here the first reproductive sterility system for the tephritid fruit fly pest,
      Anastrepha suspensa, is presented, based on lethality primarily limited to
      embryos heterozygous for a conditional lethal transgene combination. This
      tetracycline (Tet)-suppressible system uses a driver construct having the
      promoter from the newly isolated embryo-specific A. suspensa serendipity alpha
      gene linked to the Tet-transactivator. This was used to drive expression of a
      phosphomutated variant of the pro-apoptotic cell death gene, hid, from A. ludens,
      that was isolated, based on its identity to A. suspensa hid. The Alhid(Ala2)
      variant was shown to have the highest cell death activity in an in vitro A.
      suspensa cell death assay compared to the orthologous genes Ashid, Dmhid, and the
      variant Dmhid(Ala5). These cell death assays also allowed a determination of the
      most-efficient driver-effector cassette combinations for use in A. suspensa
      transformants, resulting in two hybrid strains exhibiting 100% lethality. One
      strain was 96% lethal in embryos in the absence of tetracycline, with none
      surviving past the first larval instar, which is critical for pests that are most
      damaging in late-larval stages. We demonstrate that the isolation and in vitro
      validation of species-specific promoters and lethal effector genes can greatly
      improve the efficiency of creating high-performance conditional lethality strains
      that may be extended to other insect pest species.

PMID- 22647611
TI  - Transiently populated intermediate functions as a branching point of the FF
      domain folding pathway.
AB  - Studies of protein folding and the intermediates that are formed along the
      folding pathway provide valuable insights into the process by which an unfolded
      ensemble forms a functional native conformation. However, because intermediates
      on folding pathways can serve as initiation points of aggregation (implicated in
      a number of diseases), their characterization assumes an even greater importance.
      Establishing the role of such intermediates in folding, misfolding, and
      aggregation remains a major challenge due to their often low populations and
      short lifetimes. We recently used NMR relaxation dispersion methods and
      computational techniques to determine an atomic resolution structure of the
      folding intermediate of a small protein module--the FF domain--with an
      equilibrium population of 2-3% and a millisecond lifetime, 25  degrees C. Based
      on this structure a variant FF domain has been designed in which the native state
      is selectively destabilized by removing the carboxyl-terminal helix in the native
      structure to produce a highly populated structural mimic of the intermediate
      state. Here, we show via solution NMR studies of the designed mimic that the
      mimic forms distinct conformers corresponding to monomeric and dimeric (K(d) =
      0.2 mM) forms of the protein. The conformers exchange on the seconds timescale
      with a monomer association rate of 1.1 . 10(4) M(-1) s(-1) and with a region
      responsible for dimerization localized to the amino-terminal residues of the FF
      domain. This study establishes the FF domain intermediate as a central player in
      both folding and misfolding pathways and illustrates how incomplete folding can
      lead to the formation of higher-order structures.

PMID- 22647612
TI  - Interface control of bulk ferroelectric polarization.
AB  - The control of material interfaces at the atomic level has led to novel
      interfacial properties and functionalities. In particular, the study of polar
      discontinuities at interfaces between complex oxides lies at the frontier of
      modern condensed matter research. Here we employ a combination of experimental
      measurements and theoretical calculations to demonstrate the control of a bulk
      property, namely ferroelectric polarization, of a heteroepitaxial bilayer by
      precise atomic-scale interface engineering. More specifically, the control is
      achieved by exploiting the interfacial valence mismatch to influence the
      electrostatic potential step across the interface, which manifests itself as the
      biased-voltage in ferroelectric hysteresis loops and determines the ferroelectric
      state. A broad study of diverse systems comprising different ferroelectrics and
      conducting perovskite underlayers extends the generality of this phenomenon.

PMID- 22647613
TI  - Power to the people: a wiki-governance model for biobanks.
AB  - Biobanks are adopting various modes of public engagement to close the agency gap
      between participants and biobank builders. We propose a wiki-governance model for
      biobanks that harnesses Web 2.0, and which gives citizens the ability to
      collaborate in biobank governance and policymaking.

PMID- 22647614
TI  - The histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates
      human astrocyte neurotoxicity induced by interferon-gamma.
AB  - BACKGROUNDS: Increasing evidence shows that the histone deacetylase inhibitor
      suberoylanilide hydroxamic acid (SAHA) possesses potent anti-inflammatory and
      immunomodulatory properties. It is tempting to evaluate the potential of SAHA as
      a therapeutic agent in various neuroinflammatory and neurodegenerative disorders.
      METHODS: We examined the effects of SAHA on interferon (IFN)-gamma-induced
      neurotoxicity of human astrocytes and on IFN-gamma-induced phosphorylation of
      signal transducer and activator of transcription (STAT) 3 in human astrocytes. We
      also studied the effects of SAHA on the astrocytic production of two
      representative IFN-gamma-inducible inflammatory molecules, namely IFN-gamma
      inducible T cell alpha chemoattractant (I-TAC) and intercellular adhesion
      molecule-1 (ICAM-1). RESULTS: SAHA significantly attenuated the toxicity of
      astrocytes activated by IFN-gamma towards SH-SY5Y human neuronal cells. In the
      IFN-gamma-activated astrocytes, SAHA reduced the STAT3 phosphorylation. SAHA also
      inhibited the IFN-gamma-induced astrocytic production of I-TAC, but not ICAM-1.
      These results indicate that SAHA suppresses IFN-gamma-induced neurotoxicity of
      human astrocytes through inhibition of the STAT3 signaling pathway. CONCLUSION:
      Due to its anti-neurotoxic and anti-inflammatory properties, SAHA appears to have
      the therapeutic or preventive potential for a wide range of neuroinflammatory
      disorders associated with activated astrocytes.

PMID- 22647616
TI  - Whose side are you on: does serotonin preferentially activate the right
      hemisphere and norepinephrine the left?
AB  - Serotonin (5-HT) and norepinephrine (NE) innervate both the left and right
      hemispheres of the brain, but whether they affect lateralization of function is
      unknown. This paper concisely examines evidence that these two neurotransmitters
      differentially affect the two hemispheres, and puts forth the novel hypothesis 5
      HT preferentially activates the right hemisphere (RH) and NE the left hemisphere
      (LH). The principal lines of evidence comprise studies of: (1) 5-HT and NE level
      measurement, (2) receptor binding, (3) functional brain imaging, (4) dichotic
      listening, and (5) electroencephalography and evoked potentials. In assessing
      these 5 lines, emphasis is placed on studies of pharmaceutical drugs that affect
      the 5-HT and NE systems. While all of the data do not support the hypothesis,
      they are generally consistent with it, or a variant of the hypothesis that there
      is a bias toward 5-HT preferentially activating a majority of brain areas or
      functions in the RH, and NE a majority of LH areas or functions. If this
      hypothesis, or a variant of it, is correct, it may be relevant to understanding
      the physiological basis of neuropsychiatric disorders that could involve
      dysfunction in brain monoaminergic systems, as well as understanding potential
      lateralization of the effects of drugs that act on these systems.

PMID- 22647615
TI  - Direct molecular interactions between HMGB1 and TP53 in colorectal cancer.
AB  - Tumorigenesis and the efficacy of cancer therapeutics are both defined by the
      balance between autophagy and apoptosis. High-mobility group box 1 (HMGB1) is a
      DNA chaperone and extracellular damage-associated molecular pattern molecule
      (DAMP) with pro-autophagic activity. TP53/p53 plays a transcription-dependent and
      -independent role in the regulation of apoptosis, autophagy, metabolism, cell
      cycle progression, and many other processes. Both HMGB1 and TP53 are tightly
      linked with the development of cancer, associated with many of the hallmarks
      defining the altered biology of cancer. We have demonstrated that TP53-HMGB1
      complexes regulate the balance between apoptosis and autophagy through regulation
      of the cytosolic localization of the reciprocal binding partner, whereby
      increased cytosolic HMGB1 enhances autophagy and increased cytosolic TP53
      enhances apoptosis in colon cancer cells. We found that HMGB1-mediated autophagy
      promotes cell survival in TP53-dependent processes, and that TP53 inhibits
      autophagy through negative regulation of HMGB1-BECN1 complexes. Nuclear
      localization of TP53 and HMGB1 in tumors from patients with colon adenocarcinoma
      had a positive trend with survival time from diagnosis. Thus, HMGB1 and TP53 are
      critical in the cross-regulation of apoptosis and autophagy and central to colon
      cancer biology.

PMID- 22647617
TI  - Bmp2 regulates the interaction between EPDCs and myocytes in cardiac OFT.
AB  - Epicardium-derived cells (EPDCs) can migrate into the myocardium, giving rise to
      several types of cell which are indispensable to compact myocardium and inducing
      normal myocardial development. Subepicardium accumulates bone morphogenetic
      proteins (Bmps), which can release into myocardium further. It has been shown
      that reduced Bmp-mediated signaling in a novel neural crest derivative in the
      epicardium reduced the cardiomyocyte proliferative activity in the developing
      myocardium. Furthermore, studies have demonstrated that cardiomyocytes can
      develop in proepicardial organ (PEO) explant cultures after stimulation with bone
      morphogenetic protein (Bmp2). We present a hypothesis that Bmp2 regulates the
      interaction between EPDCs and cardiomyocyte in the developing outflow tract
      (OFT). Our previous empirical data also shows that Bmp2 is expressed in the
      myocardial cell in the OFT at embryonic day (E) 14.5 in wild-type mice, and
      expression of Bmp2 in Cx43alpha1 knockout (KO) OFT was delayed for 1day. Further
      validation of this hypothesis will provide additional insight of the molecular
      mechanism of myocardium maturation.

PMID- 22647618
TI  - Epilepsy as a pyridoxine-dependent condition: quantified urinary biomarkers for
      status evaluation and monitoring antiepileptic treatment.
AB  - The study testifies an assumption on epilepsy as an inborn error of pyridoxine
      metabolism and suggests non-invasive quantitative biomarkers for clarified
      evaluation of clinical status and monitoring an individual treatment by
      antiepileptic drugs. Urinary parameters of pyridoxal-phosphate (PLP)-dependent
      tryptophan degradation and the level of 4-pyridoxic acid, the end product of
      pyridoxine metabolism, were measured by HPLC method with simultaneous ultraviolet
      and fluorimetric detection in children with different forms of epilepsy and
      matched healthy controls. The concentrations of compounds formed or metabolized
      in the course of tryptophan degradation (kynurenines, indoxyl-sulfate) along with
      correlations between them turned out to be quantitative biomarkers useful for
      both clarifying patient's clinical state and monitoring antiepileptic treatment.
      In particular, the value of the ratio of 4-pyridoxic acid to kynurenine appears
      to be an index of an experienced seizure attack, while the ratio of 3
      hydroxyanthranilic acid to 3-hydroxykynurenine reflects activity of kynureninase,
      the enzyme of critical sensitivity to PLP supply. Growing progressively worse,
      epilepsy is accompanied by aggravation of PLP-dependent disturbances of
      tryptophan metabolism and expanding inhibition of kynureninase. The affected
      pyridoxine metabolism is discussed as an inborn genetic trait in epilepsy in
      general, rather than a specific sign of pyridoxine-dependent epilepsy solely.

PMID- 22647619
TI  - Changes in the modulation of retinocollicular transmission through group III
      mGluRs long after an increase in intraocular pressure in a rat model of glaucoma.
AB  - Metabotropic glutamate receptors (mGluRs) have been shown to be involved in the
      modulation of retinocollicular neurotransmission. In glaucoma, retinal ganglion
      cells (RGCs) degenerate, which may have an implication on this transmission as
      the superior colliculus is their major central target in the much-used rodent
      models of the disease. We have investigated this using an in vitro slice
      preparation of the superior colliculus by eliciting field excitatory postsynaptic
      potentials (fEPSPs) through optic tract stimulation in a rat ocular hypertension
      model of glaucoma. Application of the group III mGluR agonist L-AP4 reduced the
      peak amplitude of the fEPSP in superior colliculus slices through presynaptic
      mechanisms as previously shown in our lab. At 3 and 16 weeks after surgery, there
      were no significant differences in the effect of L-AP4 on fEPSP peak amplitude in
      the superior colliculus slices receiving input from the glaucomatous eyes
      [elevated intraocular pressure (IOP)] compared to those with input from the
      unoperated eyes (normal IOP). However, at 32 weeks, the fEPSP peak amplitude was
      reduced to a significantly greater degree during L-AP4 application in the
      elevated IOP slices compared to normal IOP slices. At all time points, there were
      no significant changes in the baseline amplitudes of fEPSPs or the stimulus
      intensities required to evoke fEPSPs. These results suggest that the modulation
      of synaptic transmission through group III mGluRs on RGC terminals to the
      superior colliculus is changed at later stages due to RGC degeneration through
      IOP elevation. These changes may be compensatory changes possibly through
      plasticity in the RGC terminals of surviving cells, which may be due to increases
      in the numbers of group III mGluRs. This result may have implications on further
      treatment studies carried out using these models of glaucoma as changes in the
      central visual system may need to be considered along with the retinal changes
      that occur.

PMID- 22647621
TI  - Infection and autoimmunity:  theme and variations.

PMID- 22647620
TI  - Parasite-mediated interactions within the insect vector: Trypanosoma rangeli
      strategies.
AB  - Trypanosoma rangeli is a protozoan that is non-pathogenic for humans and other
      mammals but causes pathology in the genus Rhodnius. T. rangeli and R. prolixus is
      an excellent model for studying the parasite-vector interaction, but its cycle in
      invertebrates remains unclear. The vector becomes infected on ingesting blood
      containing parasites, which subsequently develop in the gut, hemolymph and
      salivary glands producing short and large epimastigotes and metacyclic
      trypomastigotes, which are the infective forms. The importance of the T. rangeli
      cycle is the flagellate penetration into the gut cells and invasion of the
      salivary glands. The establishment of the parasite depends on the alteration of
      some vector defense mechanisms. Herein, we present our understanding of T.
      rangeli infection on the vector physiology, including gut and salivary gland
      invasions, hemolymph reactions and behavior alteration.

PMID- 22647623
TI  - [When and how to detoxify clients from methadone maintenance treatment?].
AB  - BACKGROUND: Methadone is prescribed in France as a maintenance treatment for
      heroin dependence since 1969. Nevertheless, the optimal duration of methadone
      maintenance treatment and how detoxification from methadone at the end of the
      treatment should be performed is still discussed. OBJECTIVE: To conduct a
      literature review on when and how detoxify clients from methadone maintenance
      treatment and to collect the opinion of experts in the field. DOCUMENTARY
      SOURCES: We searched the PubMed, Embase, Cochrane Library and PsycINFO databases
      on the 1966-2011 period using the keywords "methadone", "maintenance",
      "detoxification", "tapering", "cessation", "withdrawal". We also searched data in
      other addictive journals in French that are not available in those databases. We
      also collected the opinion of the physician in charge of the oldest methadone
      program in France (1969). STUDIES SELECTION: We excluded studies that used
      methadone as short time treatment of heroin withdrawal and thus selected 23
      articles. RESULTS: There is a consensus on when methadone maintenance treatment
      should be stopped, defined by the client's will to stop, the judgement from the
      physician that the client has been stable for a period of time that is long
      enough, but also the client's motivation to live his life without maintenance
      treatment. There is also a majority, among articles on how methadone treatment
      should be stopped, recommending ambulatory, practical approaches using slow
      tapering of the dose, with the ability to go back to the previous dose if needed,
      namely in case of relapse to heroin use, heavy withdrawal or psychiatric
      symptoms. LIMITS: There are few articles addressing the subject, especially
      comparing prospectively different cessation strategies. CONCLUSION: Methadone
      maintenance treatment should not necessarily be maintained all life long and can
      be stopped within its prescription setting, including medical, psychological and
      social evaluation.

PMID- 22647622
TI  - The class I PI3K/Akt pathway is critical for cancer cell survival in dogs and
      offers an opportunity for therapeutic intervention.
AB  - BACKGROUND: Using novel small-molecular inhibitors, we explored the feasibility
      of the class I PI3K/Akt/mTORC1 signaling pathway as a therapeutic target in
      canine oncology either by using pathway inhibitors alone, in combination or
      combined with conventional chemotherapeutic drugs in vitro. RESULTS: We
      demonstrate that growth and survival of the cell lines tested are predominantly
      dependent on class I PI3K/Akt signaling rather than mTORC1 signaling. In
      addition, the newly developed inhibitors ZSTK474 and KP372-1 which selectively
      target pan-class I PI3K and Akt, respectively, and Rapamycin which has been well
      established as highly specific mTOR inhibitor, decrease viability of canine
      cancer cell lines. All inhibitors demonstrated inhibition of phosphorylation of
      pathway members. Annexin V staining demonstrated that KP372-1 is a potent inducer
      of apoptosis whereas ZSTK474 and Rapamycin are weaker inducers of apoptosis.
      Simultaneous inhibition of class I PI3K and mTORC1 by ZSTK474 combined with
      Rapamycin additively or synergistically reduced cell viability whereas responses
      to the PI3K pathway inhibitors in combination with conventional drug Doxorubicin
      were cell line-dependent. CONCLUSION: This study highlighted the importance of
      class I PI3K/Akt axis signaling in canine tumour cells and identifies it as a
      promising therapeutic target.

PMID- 22647624
TI  - [Patient hotel: An alternative to conventional hospitalization].

PMID- 22647626
TI  - Navel piercing during pregnancy: a cautionary tale for the family physician, the
      obstetrician and the midwife.

PMID- 22647625
TI  - [Ischemic retinopathy in Takayasu disease].
AB  - PURPOSE: To evaluate the clinical features and fundus fluorescein angiography
      findings of Takayasu retinopathy. PATIENTS AND METHODS: A retrospective,
      descriptive study of 11 patients with proven Takayasu arteritis and ischemic
      retinopathy examined at the Department of Ophthalmology of Rabta hospital
      (Tunisia). All patients underwent a complete ophthalmic examination and
      fluorescein angiography. Systemic corticotherapy and immunosuppressive therapy
      was prescribed in all patients. Green laser photocoagulation was performed in
      cases with ischemic retinopathy. RESULTS: The mean follow-up period was 64.2
      months (range, 8-82 months). The mean age at diagnosis of ischemic retinopathy
      was 27.9 years (range, 21-39 years). The male-to-female ratio was 0.1. We
      observed all stages of Takayasu's retinopathy. The best-corrected visual acuity
      ranged from 4/10 to 10/10. Clinical improvement was notes in 54.5 of all cases.
      Blindness occurs in only one case with severe ischemic retinopathy. CONCLUSION:
      The ischemic retinopathy in Takayasu disease is due to a severe hypoperfusion of
      the retinal artery. A careful and regular clinical and angiographic monitoring
      must be performed to prevent blindness.

PMID- 22647627
TI  - A new purpose for tattoos: medical alert tattoos.
AB  - Tattooing has gained a tremendous popularity for the past twenty years. The
      motivations that drive an individual to acquire a tattoo are plentiful. Tattooing
      has also found its way in the field of medicine (corneal tattooing,
      gastrointestinal tattooing during endoscopy, permanent make-up tattooing, scar
      camouflage or radiotherapy field marking...). An emerging application of
      tattooing is for the purpose of medical identification for conditions requiring
      special attention during emergency situations, such as patients with diabetes who
      may be found unconscious due to hypoglycaemia or with allergy to specific
      medication. This new phenomenon, (practiced by patients on their own without
      medical consultation) can be found on the Internet. We review here this practice,
      which is seemingly underreported in the medical literature with its advantages
      and potential drawbacks.

PMID- 22647628
TI  - Evidence-based practice in primary care: an explorative study of nurse
      practitioners in Norway.
AB  - Evidence-based practice (EBP) has been a priority in health care in recent
      decades. However, few studies have investigated EBP in primary care. The aim of
      this study was to explore the knowledge that nurses with a bachelor's degree use
      in their clinical practice of primary care. Focus group interviews were used. The
      sample consisted of 20 nurses in primary care practice. The data were analysed
      with systematic text condensation. Our findings show that most nurses use their
      own knowledge, their colleagues' knowledge, knowledge acquired during nursing
      education, nursing literature, and guidance from expert personnel, but seldom use
      research. We recommend improving and developing the clinical practice of primary
      care. Referring to and analysing specialist and scientific data about specific
      topics may lead nurses to critically evaluate their clinical practice, and may
      enhance their theoretical and scientific knowledge related to clinical practice.

PMID- 22647629
TI  - An online tool for calculation of free-energy balance for the renal inner
      medulla.
AB  - Concentrating models of the renal inner medulla can be classified according to
      external free-energy balance into passive models (positive values) and models
      that require an external energy source (negative values). Here we introduce an
      online computational tool that implements the equations of Stephenson and
      colleagues (Stephenson JL, Tewarson RP, Mejia R. Proc Natl Acad Sci USA 71: 1618
      1622, 1974) to calculate external free-energy balance at steady state for the
      inner medulla (http://helixweb.nih.gov/ESBL/FreeEnergy). Here "external free
      energy balance" means the sum of free-energy flows in all streams entering and
      leaving the inner medulla. The program first assures steady-state mass balance
      for all components and then tallies net external free-energy balance for the
      selected flow conditions. Its use is illustrated by calculating external free
      energy balance for an example of the passive concentrating model taken from the
      original paper by Kokko and Rector (Kokko JP, Rector FC Jr. Kidney Int 2: 214
      223, 1972).

PMID- 22647631
TI  - Arterial spin labeling blood flow magnetic resonance imaging for evaluation of
      renal injury.
AB  - A multitude of evidence suggests that iodinated contrast material causes
      nephrotoxicity; however, there have been no previous studies that use arterial
      spin labeling (ASL) blood flow functional magnetic resonance imaging (fMRI) to
      investigate the alterations in effective renal plasma flow between normointensive
      and hypertensive rats following injection of contrast media. We hypothesized that
      FAIR-SSFSE arterial spin labeling MRI may enable noninvasive and quantitative
      assessment of regional renal blood flow abnormalities and correlate with disease
      severity as assessed by histological methods. Renal blood flow (RBF) values of
      the cortex and medulla of rat kidneys were obtained from ASL images postprocessed
      at ADW4.3 workstation 0.3, 24, 48, and 72 h before and after injection of
      iodinated contrast media (6 ml/kg). The H&E method for morphometric measurements
      was used to confirm the MRI findings. The RBF values of the outer medulla were
      lower than those of the cortex and the inner medulla as reported previously.
      Iodinated contrast media treatment resulted in decreases in RBF in the outer
      medulla and cortex in spontaneously hypertensive rats (SHR), but only in the
      outer medulla in normotensive rats. The iodinated contrast agent significantly
      decreased the RBF value in the outer medulla and the cortex in SHR compared with
      normotensive rats after injection of the iodinated contrast media. Histological
      observations of kidney morphology were also consistent with ASL perfusion
      changes. These results demonstrate that the RBF value can reflect changes of
      renal perfusion in the cortex and medulla. ASL-MRI is a feasible and accurate
      method for evaluating nephrotoxic drugs-induced kidney damage.

PMID- 22647630
TI  - Human SLC2A9a and SLC2A9b isoforms mediate electrogenic transport of urate with
      different characteristics in the presence of hexoses.
AB  - Human SLC2A9 (GLUT9) is a novel high-capacity urate transporter belonging to the
      facilitated glucose transporter family. In the present study, heterologous
      expression in Xenopus oocytes has allowed us to undertake an in-depth radiotracer
      flux and electrophysiological study of urate transport mediated by both isoforms
      of SLC2A9 (a and b). Addition of urate to SLC2A9-producing oocytes generated
      outward currents, indicating electrogenic transport. Urate transport by SLC2A9
      was voltage dependent and independent of the Na(+) transmembrane gradient. Urate
      induced outward currents were affected by the extracellular concentration of Cl(
      ), but there was no evidence for exchange of the two anions. [(14)C]urate flux
      studies under non-voltage-clamped conditions demonstrated symmetry of influx and
      efflux, suggesting that SLC2A9 functions in urate efflux driven primarily by the
      electrochemical gradient of the cell. Urate uptake in the presence of
      intracellular hexoses showed marked differences between the two isoforms,
      suggesting functional differences between the two splice variants. Finally, the
      permeant selectivity of SLC2A9 was examined by testing the ability to transport a
      panel of radiolabeled purine and pyrimidine nucleobases. SLC2A9 mediated the
      uptake of adenine in addition to urate, but did not function as a generalized
      nucleobase transporter. The differential expression pattern of the two isoforms
      of SLC2A9 in the human kidney's proximal convoluted tubule and its electrogenic
      transport of urate suggest that these transporters play key roles in the
      regulation of plasma urate levels and are therefore potentially important
      participants in hyperuricemia and hypouricemia.

PMID- 22647632
TI  - Functional role of sodium glucose transporter in high glucose-mediated
      angiotensin type 1 receptor downregulation in human proximal tubule cells.
AB  - Previously, we have demonstrated human angiotensin type 1 receptor (hAT(1)R)
      promoter architecture with regard to the effect of high glucose (25 mM)-mediated
      transcriptional repression in human proximal tubule epithelial cells (hPTEC;
      Thomas BE, Thekkumkara TJ. Mol Biol Cell 15: 4347-4355, 2004). In the present
      study, we investigated the role of glucose transporters in high glucose-mediated
      hAT(1)R repression in primary hPTEC. Cells were exposed to normal glucose (5.5
      mM) and high glucose (25 mM), followed by determination of hyperglycemia-mediated
      changes in receptor expression and glucose transporter activity. Exposure of
      cells to high glucose resulted in downregulation of ANG II binding (4,034 +/-
      163.3 to 1,360 +/- 154.3 dpm/mg protein) and hAT(1)R mRNA expression (reduced
      60.6 +/- 4.643%) at 48 h. Under similar conditions, we observed a significant
      increase in glucose uptake (influx) in cells exposed to hyperglycemia. Our data
      indicated that the magnitude of glucose influx is concentration and time
      dependent. In euglycemic cells, inhibiting sodium-glucose cotransporters (SGLTs)
      with phlorizin and facilitative glucose transporters (GLUTs) with phloretin
      decreased glucose influx by 28.57 +/- 0.9123 and 54.33 +/- 1.202%, respectively.
      However, inhibiting SGLTs in cells under hyperglycemic conditions decreased
      glucose influx by 53.67 +/- 2.906%, while GLUT-mediated glucose uptake remained
      unaltered (57.67 +/- 3.180%). Furthermore, pretreating cells with an SGLT
      inhibitor reversed high glucose-mediated downregulation of the hAT(1)R,
      suggesting an involvement of SGLT in high glucose-mediated hAT(1)R repression.
      Our results suggest that in hPTEC, hyperglycemia-induced hAT(1)R downregulation
      is largely mediated through SGLT-dependent glucose influx. As ANG II is an
      important modulator of hPTEC transcellular sodium reabsorption and function,
      glucose-mediated changes in hAT(1)R gene expression may participate in the
      pathogenesis of diabetic renal disease.

PMID- 22647633
TI  - Differential effects of extracellular ATP on chloride transport in cortical
      collecting duct cells.
AB  - Extracellular ATP in the cortical collecting duct can inhibit epithelial sodium
      channels (ENaC) but also stimulate calcium-activated chloride channels (CACC).
      The relationship between ATP-mediated regulation of ENaC and CACC activity in
      cortical collecting duct cells has not been clearly defined. We used the
      mpkCCD(c14) cortical collecting duct cell line to determine effects of ATP on
      sodium (Na(+)) and chloride (Cl(-)) transport with an Ussing chamber system. ATP,
      at a concentration of 10(-6) M or less, did not inhibit ENaC-mediated short
      circuit current (I(sc)) but instead stimulated a transient increase in I(sc). The
      macroscopic current-voltage relationship for ATP-inducible current demonstrated
      that the direction of this ATP response changes from positive to negative when
      transepithelial voltage (V(te)) is clamped to less than -10 mV. We hypothesized
      that this negative V(te) might be found under conditions of aldosterone
      stimulation. We next stimulated mpkCCD(c14) cells with aldosterone (10(-6) M) and
      then clamped the V(te) to -50 mV, the V(te) of aldosterone-stimulated cells under
      open-circuit conditions. ATP (10(-6) M) induced a transient increase in negative
      clamp current, which could be inhibited by flufenamic acid (CACC inhibitor) and
      BAPTA-AM (calcium chelator), suggesting that ATP stimulates Cl(-) absorption
      through CACC. Together, our findings suggest that the status of ENaC activity, by
      controlling V(te), may dictate the direction of ATP-stimulated Cl(-) transport.
      This interplay between aldosterone and purinergic signaling pathways may be
      relevant for regulating NaCl transport in cortical collecting duct cells under
      different states of extracellular fluid volume.

PMID- 22647634
TI  - Ca(2+)/calmodulin-dependent protein kinase II is associated with pelvic pain of
      neurogenic cystitis.
AB  - Interstitial cystitis/painful bladder syndrome is a chronic bladder inflammatory
      disease of unknown etiology that is often regarded as a neurogenic cystitis.
      Interstitial cystitis is associated with urothelial lesions, voiding dysfunction,
      and pain in the pelvic/perineal area. In this study, we used a murine neurogenic
      cystitis model to identify genes participating in the development of pelvic pain.
      Neurogenic cystitis was induced by the injection of Bartha's strain of
      pseudorabies virus (PRV) into the abductor caudalis dorsalis (tail base) muscle
      of female C57BL/6J mice. Mice infected with PRV developed progressive pelvic
      pain. The sacral spinal cord was harvested on postinfection days (PID) 2 and 4,
      and gene expression was analyzed by microarrays and confirmed by quantitative RT
      PCR. On PID 2, the overall expression profile was similar to that of uninfected
      sacral spinal cord; by PID 4, there were substantial differences in expression of
      multiple functional classes of genes, especially inflammation. Analysis of pain
      signaling pathways at the dorsal horn suggested that Ca(2+)/calmodulin-dependent
      protein kinase II (CaMKII) contributes to neurogenic cystitis pelvic pain.
      Consistent with this, CaMKIIdelta expression exhibited a mast cell-dependent
      increase in the sacral spinal cord at the mRNA level, and phospho-CaMKII
      immunoreactivity in the dorsal horn was increased on postinfection day (PID) 4
      during PRV infection. Finally, intrathecal injection of the CaMKII inhibitor KN
      93 attenuated the PRV pain response. These data suggest that CaMKII plays a
      functional role in pelvic pain due to neurogenic cystitis.

PMID- 22647635
TI  - Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone.
AB  - Fibroblast growth factor 23 (FGF23) significantly increases with declining renal
      function, leading to reduced renal tubular phosphate reabsorption, decreased 1,25
      dihydroxyvitamin D, and increased left ventricular hypertrophy. Elevated FGF23 is
      associated with increased mortality. FGF23 is synthesized in osteoblasts and
      osteocytes; however, the mechanisms by which it is regulated are not clear.
      Patients with chronic kidney disease have decreased renal acid excretion leading
      to metabolic acidosis, which has a direct effect on bone cell activity. We
      hypothesized that metabolic acidosis would directly increase bone cell FGF23
      production. Using cultured neonatal mouse calvariae, we found that metabolic
      acidosis increased medium FGF23 protein levels as well as FGF23 RNA expression at
      24 h and 48 h compared with incubation in neutral pH medium. To exclude that the
      increased FGF23 was secondary to metabolic acidosis-induced release of bone
      mineral phosphate, we cultured primary calvarial osteoblasts. In these cells,
      metabolic acidosis increased FGF23 RNA expression at 6 h compared with incubation
      in neutral pH medium. Thus metabolic acidosis directly increases FGF23 mRNA and
      protein in mouse bone. If these results are confirmed in humans with chronic
      kidney disease, therapeutic interventions to mitigate acidosis, such as
      bicarbonate administration, may also lower levels of FGF23, decrease left
      ventricular hypertrophy, and perhaps even decrease mortality.

PMID- 22647637
TI  - Current state of knowledge: the canine gastrointestinal microbiome.
AB  - Gastrointestinal (GI) microbes have important roles in the nutritional,
      immunological, and physiologic processes of the host. Traditional cultivation
      techniques have revealed bacterial density ranges from 10(4) to 10(5) colony
      forming units (CFU)/g in the stomach, from 10(5) to 10(7) CFU/g in the small
      intestine, and from 10(9) to 10(11) CFU/g in the colon of healthy dogs. As a
      small number of bacterial species can be grown and studied in culture, however,
      progress was limited until the recent emergence of DNA-based techniques. In
      recent years, DNA sequencing technology and bioinformatics have allowed for
      better phylogenetic and functional/metabolic characterization of the canine gut
      microbiome. Predominant phyla include Firmicutes, Bacteroidetes, Fusobacteria,
      Proteobacteria, and Actinobacteria. Studies using 16S ribosomal RNA (rRNA) gene
      pyrosequencing have demonstrated spatial differences along the GI tract and among
      microbes adhered to the GI mucosa compared to those in intestinal contents or
      feces. Similar to humans, GI microbiome dysbiosis is common in canine GI diseases
      such as chronic diarrhea and inflammatory bowel diseases. DNA-based assays have
      also identified key pathogens contributing to such conditions, including various
      Clostridium, Campylobacter, Salmonella, and Escherichia spp. Moreover,
      nutritionists have applied DNA-based techniques to study the effects of dietary
      interventions such as dietary fiber, prebiotics, and probiotics on the canine GI
      microbiome and associated health indices. Despite recent advances in the field,
      the canine GI microbiome is far from being fully characterized and a deeper
      characterization of the phylogenetic and functional/metabolic capacity of the GI
      microbiome in health and disease is needed. This paper provides an overview of
      recent studies performed to characterize the canine GI microbiome.

PMID- 22647636
TI  - HIV-induced kidney cell injury: role of ROS-induced downregulated vitamin D
      receptor.
AB  - Reactive oxygen species (ROS) have been demonstrated to contribute to HIV-induced
      tubular cell injury. We hypothesized that HIV-induced ROS generation may be
      causing tubular cell injury through downregulation of vitamin D receptor (VDR)
      and associated downstream effects. In the present study, HIV not only
      downregulated tubular cell VDR expression but also inflicted DNA injury. On the
      other hand, EB-1089, a VDR agonist (VD), inhibited both downregulation of VDR and
      tubular cell DNA injury in the HIV milieu. H(2)O(2) (an O(-) donor) directly
      downregulated tubular cell VDR, whereas catalase, a free radical scavenger,
      inhibited HIV-induced downregulation of tubular cell VDR expression. HIV also
      stimulated the tubular cell renin-angiotensin system (RAS) through downregulation
      of VDR. Because losartan (an ANG II blolcker) partially inhibited HIV-induced
      tubular cell ROS generation while ANG II directly stimulated tubular cell ROS
      generation, it appears that HIV-induced ROS production was partly contributed by
      the RAS activation. VD not only inhibited HIV-induced RAS activation but also
      attenuated tubular cell ROS generation. Tubular cells displayed double jeopardy
      in the HIV milieu induction of double-strand breaks and attenuated DNA repair;
      additionally, in the HIV milieu, tubular cells exhibited enhanced expression of
      phospho-p53 and associated downstream signaling. A VDR agonist and an ANG II
      blocker not only preserved expression of tubular cell DNA repair proteins but
      also inhibited induction of double-strand breaks. In in vivo studies, renal
      cortical sections of Tg26 mice displayed attenuated expression of VDR both in
      podocytes and tubular cells. In addition, renal cortical sections of Tg26 mice
      displayed enhanced oxidative stress-induced kidney cell DNA damage. These
      findings indicated that HIV-induced tubular cell downregulation of VDR
      contributed to the RAS activation and associated tubular cell DNA damage.
      However, both VD and RAS blockade provided protection against these effects of
      HIV.

PMID- 22647639
TI  - The successful treatment of IgG4-positive colitis with adalimumab in a patient
      with IgG4-related sclerosing disease--a new subtype of aggressive colitis?
AB  - We present the case of a 16 year old girl who developed an aggressive colitis in
      the context of a prior biopsy proven autoimmune pancreatitis, which presented
      with obstructive jaundice at the age of 13 year. This history prompted
      prospective investigation and the discovery of compelling evidence to make a
      diagnosis of IgG4-related sclerosing disease with extra-pancreatic colonic
      involvement on the basis of raised serum IgG4 levels and a florid colonic IgG4
      plasma cell infiltrate with over 20 IgG4 positive plasma cells/hpf. The colitis
      was resistant to conventional therapy but responded dramatically to treatment
      with the anti-TNFalpha monoclonal antibody, adalimumab. This is the first case to
      report both the effectiveness of adalimumab in treating IgG4 positive colitis in
      a patient with IgG4-related sclerosing disease, and to prospectively record
      resolution of an IgG4 positive colonic infiltrate with immunosuppression.

PMID- 22647638
TI  - Pulmonary cryptococcosis in a patient with Crohn's disease treated with
      prednisone, azathioprine and adalimumab: exposure to chicken manure as a source
      of contamination.
AB  - BACKGROUND: Biotherapies targeting TNFalpha were proven to be effective in the
      most severe cases of Crohn's Disease, a chronic granulomatous inflammatory bowel
      disease that can involve any portion of the digestive tract. The tolerance of
      anti-TNFalpha therapy is usually good, although several infectious complications
      have been reported with these drugs. METHODS: We report a case of a Crohn's
      disease patient who developed pulmonary cryptococcosis following chicken manure
      exposition while he received adalimumab and azathioprine. CASE: A 54-year-old
      man, with history of severe Crohn's disease and ankylosing spondylitis, was
      admitted for diarrhea and abdominal pain under azathioprine treatment. In
      December 2010, he was treated with oral prednisone (1 mg/kg/day), but Crohn's
      disease relapsed when prednisone dose was lower than 30 mg/a day. The patient was
      then treated with adalimumab, but six weeks later he developed severe pulmonary
      cryptococcosis. The patient experienced a good outcome under antifungal therapy.
      We retrospectively found a high exposure to chicken manure in the last weeks.
      CONCLUSION: Cryptococcosis is an opportunistic infection that can occur under
      anti-TNFalpha therapy. The environmental exposure to Cryptococcus spp. (in
      particular in chicken manure) is a source of contamination. Avoiding exposition
      to bird manure should be a recommendation for patients who are living in rural
      areas.

PMID- 22647640
TI  - [Depressor anguli oris sign (DAO) in facial paresis. How to search it and release
      the smile (technical note)].
AB  - INTRODUCTION: After facial paralysis recovery, it is common to note a co
      contraction between depressor anguli oris (DAO) muscle and zygomatic muscles.
      This DAO co-contraction will "obstruct" the patient's smile. The purpose of this
      technical note is to show how to find the DAO sign and how to free up the smile.
      TECHNICAL: This co-contraction between the zygomatic muscles and DAO research is
      placing a finger on marionette line, asking the patient to smile: we perceive a
      rope under the skin corresponding to the abnormal contraction and powerful DAO. A
      diagnostic test with lidocaine injection into the DAO can be performed to confirm
      the diagnosis. The treatment of pathological DAO's contraction can be by
      injection of botulinum toxin in the DAO, or by surgical myectomy. In all cases, a
      speech therapy complete the treatment. CONCLUSION: The DAO sign is a semiological
      entity easy to find. His treatment releases smile without negative effect on the
      facial expression as the DAO is especially useful in the expression of disgust.

PMID- 22647641
TI  - Motor control is decision-making.
AB  - Motor behavior may be viewed as a problem of maximizing the utility of movement
      outcome in the face of sensory, motor and task uncertainty. Viewed in this way,
      and allowing for the availability of prior knowledge in the form of a probability
      distribution over possible states of the world, the choice of a movement plan and
      strategy for motor control becomes an application of statistical decision theory.
      This point of view has proven successful in recent years in accounting for
      movement under risk, inferring the loss function used in motor tasks, and
      explaining motor behavior in a wide variety of circumstances.

PMID- 22647643
TI  - Critical wavefunctions in disordered graphene.
AB  - In order to elucidate the presence of non-localized states in doped graphene, a
      scaling analysis of the wavefunction moments, known as inverse participation
      ratios, is performed. The model used is a tight-binding Hamiltonian considering
      nearest and next-nearest neighbors with random substitutional impurities. Our
      findings indicate the presence of non-normalizable wavefunctions that follow a
      critical (power-law) decay, which show a behavior intermediate between those of
      metals and insulators. The power-law exponent distribution is robust against the
      inclusion of next-nearest neighbors and growing the system size.

PMID- 22647642
TI  - Spontaneously hypertensive rats display reduced microglial activation in response
      to ischemic stroke and lipopolysaccharide.
AB  - BACKGROUND: For successful translation to clinical stroke studies, the Stroke
      Therapy Academic Industry Round Table criteria have been proposed. Two important
      criteria are testing of therapeutic interventions in conscious animals and the
      presence of a co-morbidity factor. We chose to work with hypertensive rats since
      hypertension is an important modifiable risk factor for stroke and influences the
      clinical outcome. We aimed to compare the susceptibility to ischemia in
      hypertensive rats with those in normotensive controls in a rat model for
      induction of ischemic stroke in conscious animals. METHODS: The vasoconstrictor
      endothelin-1 was stereotactically applied in the vicinity of the middle cerebral
      artery of control Wistar Kyoto rats (WKYRs) and spontaneously hypertensive rats
      (SHRs) to induce a transient decrease in striatal blood flow, which was measured
      by the laser Doppler technique. Infarct size was assessed histologically by
      cresyl violet staining. Sensory-motor functions were measured at several time
      points using the neurological deficit score. Activation of microglia and
      astrocytes in the striatum and cortex was investigated by immunohistochemistry
      using antibodies against CD68/Iba-1 and glial fibrillary acidic protein. RESULTS
      AND CONCLUSIONS: The SHRs showed significantly larger infarct volumes and more
      pronounced sensory-motor deficits, compared to the WKYRs at 24 h after the
      insult. However, both differences disappeared between 24 and 72 h. In SHRs,
      microglia were less susceptible to activation by lipopolysaccharide and there was
      a reduced microglial activation after induction of ischemic stroke. These
      quantitative and qualitative differences may be relevant for studying the
      efficacy of new treatments for stroke in accordance to the Stroke Therapy
      Academic Industry Round Table criteria.

PMID- 22647644
TI  - Occurrence and concentration of caffeine in Oregon coastal waters.
AB  - Caffeine, a biologically active drug, is recognized as a contaminant of
      freshwater and marine systems. We quantified caffeine concentrations in Oregon's
      coastal ocean to determine whether levels correlated with proximity to caffeine
      pollution sources. Caffeine was analyzed at 14 coastal locations, stratified
      between populated areas with sources of caffeine pollution and sparsely populated
      areas with no major caffeine pollution sources. Caffeine concentrations were
      measured in major water bodies discharging near sampling locations. Caffeine in
      seawater ranged from below the reporting limit (8.5 ng/L) to 44.7 ng/L. Caffeine
      occurrence and concentrations in seawater did not correspond with pollution
      threats from population density and point and non-point sources, but did
      correspond with storm event occurrence. Caffeine concentrations in rivers and
      estuaries draining to the coast ranged from below the reporting limit to 152.2
      ng/L. This study establishes the occurrence of caffeine in Oregon's coastal
      waters, yet relative importance of sources, seasonal variability, and processes
      affecting caffeine transport into the coastal ocean require further research.

PMID- 22647645
TI  - Pollutant impacts to Cape Hatteras National Seashore from urban runoff and septic
      leachate.
AB  - The sandy barrier islands of Cape Hatteras National Seashore, USA, attract large
      seasonal influxes of tourists, and are host to numerous motels, rentals and
      second homes. To investigate the impacts of nearby urbanization on public trust
      waters, sampling was conducted in nine brackish water bodies within this coastal
      national park. A large tidal urban ditch delivered runoff-driven fecal
      contaminated water directly into public beach waters. At all sites except the
      control, ammonium, phosphorus and fecal bacteria concentrations were high,
      strongly seasonal and significantly correlated with community water usage,
      indicating that increased septic tank usage led to increased pollutant
      concentrations in area waterways. Nutrients from septic systems caused ecosystem
      level problems from algal blooms, BOD, and hypoxia while fecal microbes created
      potential human health problems. Septic system usage is widespread in sensitive
      coastal areas with high water tables and sandy soils and alternatives to standard
      septic systems must be required to protect human health and the environment.

PMID- 22647646
TI  - The relationship between attitudes to aging and physical and mental health in
      older adults.
AB  - BACKGROUND: Attitudes are known to exert a powerful influence on a range of
      behaviors. The objective of this study was to investigate the contribution of
      attitudes toward one's own aging to satisfaction with life and physical and
      mental health measured in a sample of community-dwelling older adults. METHODS:
      Adults who were part of a larger study of health and well-being in rural and
      regional Australia aged >=60 years (N = 421) completed a cross-sectional postal
      survey comprising the Attitudes to Aging Questionnaire, the 12-Item Short Form
      Health Survey (SF-12), the Satisfaction with Life Scale, the Geriatric Anxiety
      Inventory, and the Center for Epidemiological Studies Depression Scale. RESULTS:
      Overall, attitudes to aging were positive in this sample. More positive attitudes
      to aging were associated with higher levels of satisfaction with life, better
      self-report physical and mental health on the SF-12, and lower levels of anxiety
      and depression, after controlling for confounding variables. Better financial
      status and being employed were both associated with more positive attitudes to
      aging and better self-reported physical health. Relationship status was also
      significantly associated with mental health and satisfaction with life, but not
      physical health. CONCLUSION: The promotion of successful aging is increasingly
      becoming important in aging societies. Having positive attitudes to aging may
      contribute to healthier mental and physical outcomes in older adults. Overcoming
      negative stereotypes of aging through change at the societal and individual level
      may help to promote more successful aging.

PMID- 22647648
TI  - Robotic approaches to prolapse surgery.
AB  - PURPOSE OF REVIEW: Pelvic reconstructive surgeons in the fields of urology,
      gynecology and urogynecology have continually adapted new techniques in pelvic
      organ prolapse (POP) repair in order to improve both anatomic and subjective
      outcomes. In the last 5 years, robotic surgery has gained a strong foothold in
      urologic oncology, gynecologic oncology, cardiothoracic surgery and now in female
      pelvic medicine. Robotic surgery has made its way into the armamentarium of POP
      treatment and has allowed pelvic surgeons to adapt the 'gold standard' technique
      of abdominal sacrocolpopexy to a minimally invasive approach with improved
      intraoperative morbidity and decreased convalescence. This review article aims to
      discuss the techniques of robotic prolapse repair as well as morbidity, cost and
      clinical outcomes. RECENT FINDINGS: The adaptation of minimally invasive
      approaches to the treatment of POP initially began with laparoscopy, something
      only those surgeons with extensive and advanced laparoscopic skills are able to
      accomplish. Access to robotic technology makes conversion from open or
      laparoscopic to robotic surgery much more feasible for most pelvic floor
      surgeons. There are currently no published randomized, controlled trials
      comparing robotic with open or laparoscopic sacrocolpopexy, however, there are
      several publications reporting both retrospective and prospective series of women
      undergoing robotic-assisted sacrocolpopexy. SUMMARY: Robotic-assisted pelvic
      floor surgery has become an important component of the pelvic surgeon's
      armamentarium in the treatment of symptomatic POP. Those pelvic surgeons without
      significant expertise in laparoscopy required for sacral dissection and
      intracorporeal suturing can readily learn the necessary techniques required for
      robotic surgery.

PMID- 22647647
TI  - Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in
      monoarthritic rats.
AB  - BACKGROUND: Spinal glia, particularly microglia and astrocytes, are of the utmost
      importance in the development and maintenance of chronic pain. A recent study
      from our laboratory revealed that gabapentin, a recommended first-line treatment
      for multiple neuropathic conditions, could also efficiently antagonize thermal
      hyperalgesia evoked by complete Freund's adjuvant (CFA)-induced monoarthritis
      (MA). In the present study, we investigated whether the spinal glia are involved
      in the anti-hyperalgesic effect of gabapentin and how this event occurs. RESULTS:
      Unilateral intra-articular injection of CFA produced a robust activation of
      microglia and astrocytes. These cells exhibited large cell bodies, thick
      processes and increases in the ionized calcium binding adapter molecule 1 (Iba-1,
      a microglial marker) or the glia fibrillary acidic protein (GFAP, an astrocytic
      marker). These cells also displayed immunoreactive signals, and an upregulation
      of the voltage-gated calcium channels (VGCCs) alpha2/delta-1 subunit, CX3CL1 and
      CX3CR1 expression levels in the spinal cord. These changes were associated with
      the development of thermal hyperalgesia. Immunofluorescence staining showed that
      VGCC alpha2/delta-1 subunit, a proposed gabapentin target of action, was widely
      distributed in primary afferent fibers terminals and dorsal horn neurons. CX3CL1,
      a potential trigger to activate microglia, colocalized with VGCC alpha2/delta-1
      subunits in the spinal dorsal horn. However, its receptor CX3CR1 was mainly
      expressed in the spinal microglia. Multiple intraperitoneal (i.p.) gabapentin
      injections (100 mg/kg, once daily for 4 days with the first injection 60 min
      before intra-articular CFA) suppressed the activation of spinal microglia,
      downregulated spinal VGCC alpha2/delta-1 subunits decreased CX3CL1 levels and
      blocked the development of thermal hyperalgesia in MA rats. CONCLUSIONS: Here we
      provide the first evidence that gabapentin diminishes CX3CL1 signaling and spinal
      microglia activation induced by joint inflammation. We also show that the VGCC
      alpha2/delta-1 subunits might be involved in these events.

PMID- 22647649
TI  - Image guidance in the focal treatment of prostate cancer.
AB  - PURPOSE OF REVIEW: The advent of prostate-specific antigen screening has led to a
      seven-fold increase in the incidence of prostate cancer without a resultant
      decrease in mortality rate. This has led to the belief that urologists are
      overdetecting and overtreating clinically insignificant disease. To maintain the
      delicate balance between high cancer cure rate and overtreatment, which could
      potentially lead to unnecessary morbidities, focal therapy has emerged as the
      reasonable middle ground. In this article, we present the conceptual basis and
      the challenges of focal therapy, while emphasizing the critical role of imaging
      in focal treatment of prostate cancer. RECENT FINDINGS: Multiple phase I trials
      have demonstrated the feasibility, short-term efficacy, and safety of focal
      therapy. Fundamental to the success of these trials and the ultimate acceptance
      of focal therapy is the integral role of imaging in optimal patient selection.
      Among the different imaging modalities, only ultrasound and multiparametric MRI
      are intimately involved in the detection, diagnosis, staging, and treatment of
      prostate cancer. Each modality has its own unique advantages and shortcomings.
      Recent advances in enhanced ultrasound modalities, functional MRIs, and biopsy
      platforms have taken focal therapy one step closer to becoming the standard of
      care. SUMMARY: Although early results of phase I focal therapy trials are
      encouraging, long-term oncological outcomes remain to be elucidated.
      Incorporation of these technological advances into large prospective trials is
      needed to establish focal therapy as an important asset in the urologist's
      armamentarium against prostate cancer.

PMID- 22647650
TI  - Tumor enucleation for small renal masses.
AB  - PURPOSE OF REVIEW: The incidence of renal cell carcinoma and the detection of
      incidental small renal masses are rising. Urologists are faced with difficult
      management decisions on how to treat patients with small renal masses.
      Traditionally, the treatment of suspicious renal masses was radical nephrectomy.
      However, nephron-sparing surgery is the standard of care, when possible, because
      of the risk of renal insufficiency associated with radical nephrectomy. RECENT
      FINDINGS: A large breadth of data have shown that partial nephrectomy has
      equivalent oncologic outcomes compared to radical nephrectomy. Recently, attempts
      to further spare renal parenchyma and perform nephron-sparing surgery in
      anatomically difficult scenarios have led to the development of the enucleation
      technique. Enucleation is performed by following the natural plane between the
      peritumor pseudocapsule and the renal parenchyma. This emerging technique was met
      with skepticism and concern for incomplete tumor removal. However, studies
      comparing enucleation and partial nephrectomy to date have revealed equivalent
      oncologic outcomes. SUMMARY: There has been a greater acceptance of tumor
      enucleation as a safe alternative for renal masses which are locally confined on
      preoperative imaging, easily delineated intraoperatively, and do not appear to
      grossly invade beyond the pseudocapsule.

PMID- 22647651
TI  - High-throughput sequencing to decipher the genetic heterogeneity of deafness.
AB  - Identifying genes causing non-syndromic hearing loss has been challenging using
      traditional approaches. We describe the impact that high-throughput sequencing
      approaches are having in discovery of genes related to hearing loss and the
      implications for clinical diagnosis.

PMID- 22647652
TI  - Predicting beef tenderness using color and multispectral image texture features.
AB  - The objective of this study was to investigate the usefulness of raw meat surface
      characteristics (texture) in predicting cooked beef tenderness. Color and
      multispectral texture features, including 4 different wavelengths and 217 image
      texture features, were extracted from 2 laboratory-based multispectral camera
      imaging systems. Steaks were segregated into tough and tender classification
      groups based on Warner-Bratzler shear force. The texture features were submitted
      to STEPWISE multiple regression and support vector machine (SVM) analyses to
      establish prediction models for beef tenderness. A subsample (80%) of tender or
      tough classified steaks were used to train models which were then validated on
      the remaining (20%) test steaks. For color images, the SVM model correctly
      identified tender steaks with 100% accurately while the STEPWISE equation
      identified 94.9% of the tender steaks correctly. For multispectral images, the
      SVM model predicted 91% and STEPWISE predicted 87% average accuracy of beef
      tender.

PMID- 22647653
TI  - "Chilled" pork--Part II. Consumer perception of sensory quality.
AB  - The objective of this study was to compare consumer perception of the sensory
      quality of grilled Canadian pork destined for Japanese and domestic markets, with
      particular reference to export selection criteria imposed by Japanese importers
      and transportation conditions. Consumers from Quebec, Canada tasted local and
      export quality pork subjected to "chilled" (aged 43 days at -1.7  degrees C) or
      conventional ageing (5 days at 3.1  degrees C). Consumers' scores (out of 10)
      were higher (P<0.05) in the "chilled" than conventionally aged pork for
      tenderness (6.8 vs 5.7), juiciness (6.6 vs 6.0), taste liking (6.4 vs 5.9) and
      overall acceptability (6.7 vs 6.1). When informed that the conventionally aged,
      domestic quality pork was destined for the domestic market, consumer scores
      increased significantly (P<0.05). No effect of information was observed on the
      perception of the 'chilled' export quality meat, perhaps a consequence of the
      high sensory quality observed prior to labelling.

PMID- 22647654
TI  - V/Q SPECT imaging of acute pulmonary embolus - a practical perspective.
AB  - The following article is intended to illustrate the place of scintigraphy and
      computed tomography pulmonary angiography (CTPA) in the investigation of acute PE
      in current practice, and to guide non-radionuclide radiologists and other medical
      professionals to the best test for patients. We share our early experiences with
      ventilation-perfusion (V/Q) single-photon-emission computed tomography (SPECT)
      including image acquisition and interpretation. A comparison of the two
      techniques is given, along with practical considerations in a variety of clinical
      scenarios.

PMID- 22647655
TI  - Abnormalities of the globe.
AB  - Although much has been published in the radiology literature on the multitudinous
      conditions affecting the bony orbit, there has been relatively little on diseases
      confined to the globe itself. As current cross-sectional imaging techniques
      evolve, the globes can be visualized in ever greater detail, facilitating the
      recognition of even fairly subtle disease entities in this region. Indeed, the
      fact that high-resolution detailed images of this area are achievable without
      significant time or radiation penalty when evaluating surrounding structures
      means that incidental disease is not infrequently encountered. As such, common
      disease entities in this region are of interest to the general radiologist and
      the diagnosis of globe disease need not be the remit of experienced observers in
      specialist centres. At our institutions we have recently encountered a number of
      cases covering a broad spectrum of diagnoses including traumatic, neoplastic,
      iatrogenic, inflammatory, and infective aetiologies. The purpose of this review
      is to briefly revise the pertinent anatomical and physiological properties of the
      globe and to familiarize the reader with the computed tomography (CT) and
      magnetic resonance imaging (MRI) appearances of a number of these disease states.
      The collection of abnormalities included is not intended to be exhaustive, merely
      representative, with the emphasis towards those more commonly encountered.

PMID- 22647657
TI  - Pharmaceuticals and personal care products in the environment: what are the big
      questions?
AB  - BACKGROUND: Over the past 10-15 years, a substantial amount of work has been done
      by the scientific, regulatory, and business communities to elucidate the effects
      and risks of pharmaceuticals and personal care products (PPCPs) in the
      environment. OBJECTIVE: This review was undertaken to identify key outstanding
      issues regarding the effects of PPCPs on human and ecological health in order to
      ensure that future resources will be focused on the most important areas. DATA
      SOURCES: To better understand and manage the risks of PPCPs in the environment,
      we used the "key question" approach to identify the principle issues that need to
      be addressed. Initially, questions were solicited from academic, government, and
      business communities around the world. A list of 101 questions was then discussed
      at an international expert workshop, and a top-20 list was developed. Following
      the workshop, workshop attendees ranked the 20 questions by importance. DATA
      SYNTHESIS: The top 20 priority questions fell into seven categories: a)
      prioritization of substances for assessment, b) pathways of exposure, c)
      bioavailability and uptake, d) effects characterization, e) risk and relative
      risk, f ) antibiotic resistance, and g) risk management. CONCLUSIONS: A large
      body of information is now available on PPCPs in the environment. This exercise
      prioritized the most critical questions to aid in development of future research
      programs on the topic.

PMID- 22647658
TI  - Dosimetric factors associated with pituitary function after Gamma Knife Surgery
      (GKS) of pituitary adenomas.
AB  - BACKGROUND AND PURPOSE: Gamma Knife Surgery (GKS) can be an adjunctive option to
      surgery in the case of pituitary adenomas. The effect of dosimetric variables on
      the incidence of new anterior pituitary deficits after GKS requires better
      definition. MATERIALS AND METHODS: This retrospective study considered 130
      patients with a follow up after GKS >6 months. The diagnosis was nonfunctioning
      pituitary adenoma (NFPA) in 68 patients and secreting pituitary adenoma (SPA) in
      62 patients. Median margin dose was 15/25 Gy for NFPA and SPA, respectively. The
      endocrinological median follow-up was 60 months. Hypopituitarism was defined as a
      new pituitary deficit in (at least) one of the three hormonal axes (hypogonadism,
      hypothyroidism and hypoadrenalism). The predictive value of clinical/dosimetric
      parameters was tested by univariate/multivariate analyses. RESULTS: Sixteen
      patients (12.3%) showed a new pituitary deficit in one or more axes. Multivariate
      analysis confirmed that the mean dose to the stalk/pituitary and the amount of
      healthy tissue within the high dose region were strong independent predictors of
      pituitary dysfunction; their best cut-off values were around 15.7 Gy, 7.3 Gy and
      1.4 cm(3), respectively. CONCLUSIONS: Our data showed a dose-dependent incidence
      of new hormonal deficits after GKS for pituitary adenoma. During planning
      definition, the risk of hypopituitarism could be reduced using the outlined safe
      dose-volume values.

PMID- 22647659
TI  - An analysis of patient positioning during stereotactic lung radiotherapy
      performed without rigid external immobilization.
AB  - BACKGROUND AND PURPOSE: Intra-fraction patient motion is incompletely understood
      and the optimum amount of support or immobilization during stereotactic body
      radiotherapy (SBRT) is unclear. Rigid immobilization is often advocated, but
      motion still occurs. In contrast, we deliver the vast majority of SBRT using
      simple supporting devices, simultaneously emphasizing comfort, frequent position
      checks and progressive reduction in treatment times. We report spine stability
      during lung SBRT. MATERIALS AND METHODS: Patients lie on a thin mattress with
      arms supported above their head and below-knee support. Stereoscopic spine X-rays
      before and after fraction delivery identified motion in three translational and
      three rotational directions. RESULTS: Images from 109 fractions in 30 patients
      resulted in 327 translational and 327 rotational pre- and post-fraction
      comparisons. Mean RapidArc(r) delivery time for variable fraction dose was 4.2
      min (SD=1.4). 92% and 97% of translational and rotational differences were <=1 mm
      and <=1 degrees  in any direction and 98% of translational differences were
      <=1.5mm. Mean vertical, longitudinal and lateral motion was 0mm (SD=0.4), 0mm
      (0.6) and 0mm (0.6). 84% and 94% of the 109 fractions were delivered with <=1 and
      <=1.5mm translation in all three directions and 93% with <=1 degrees  of
      rotation. Two patients accounted for 10/17 fractions with >1mm translational
      motion. CONCLUSIONS: Based on pre and post-fraction X-ray imaging during fast
      lung SBRT, simple support devices can result in spine stability that is
      comparable to that reported with rigid external immobilization.

PMID- 22647656
TI  - Autophagy in lysosomal storage disorders.
AB  - Lysosomes are ubiquitous intracellular organelles that have an acidic internal
      pH, and play crucial roles in cellular clearance. Numerous functions depend on
      normal lysosomes, including the turnover of cellular constituents, cholesterol
      homeostasis, downregulation of surface receptors, inactivation of pathogenic
      organisms, repair of the plasma membrane and bone remodeling. Lysosomal storage
      disorders (LSDs) are characterized by progressive accumulation of undigested
      macromolecules within the cell due to lysosomal dysfunction. As a consequence,
      many tissues and organ systems are affected, including brain, viscera, bone and
      cartilage. The progressive nature of phenotype development is one of the
      hallmarks of LSDs. In recent years biochemical and cell biology studies of LSDs
      have revealed an ample spectrum of abnormalities in a variety of cellular
      functions. These include defects in signaling pathways, calcium homeostasis,
      lipid biosynthesis and degradation and intracellular trafficking. Lysosomes also
      play a fundamental role in the autophagic pathway by fusing with autophagosomes
      and digesting their content. Considering the highly integrated function of
      lysosomes and autophagosomes it was reasonable to expect that lysosomal storage
      in LSDs would have an impact upon autophagy. The goal of this review is to
      provide readers with an overview of recent findings that have been obtained
      through analysis of the autophagic pathway in several types of LSDs, supporting
      the idea that LSDs could be seen primarily as "autophagy disorders."

PMID- 22647661
TI  - Point-of-care breath test for biomarkers of active pulmonary tuberculosis.
AB  - RATIONALE: Volatile organic compounds (VOCs) in breath provide biomarkers of
      tuberculosis (TB) because Mycobacterium tuberculosis manufactures VOC metabolites
      that are detectable in the breath of infected patients. OBJECTIVES: We evaluated
      breath VOC biomarkers in subjects with active pulmonary TB, using an internet
      linked rapid point-of-care breath test. METHODS: 279 subjects were studied at
      four centers in three countries, Philippines, UK, and India, and data was
      analyzed from 251 (130 active pulmonary TB, 121 controls). A point-of-care system
      collected and concentrated breath and air VOCs, and analyzed them with automated
      thermal desorption, gas chromatography, and surface acoustic wave detection. A
      breath test was completed in 6 min. Chromatograms were converted to a series of
      Kovats Index (KI) windows, and biomarkers of active pulmonary TB were identified
      by Monte Carlo analysis of KI window alveolar gradients (abundance in breath
      minus abundance in room air). MEASUREMENTS AND MAIN RESULTS: Multiple Monte Carlo
      simulations identified eight KI windows as biomarkers with better than random
      performance. Four KI windows corresponded with KI values of VOCs previously
      identified as biomarkers of pulmonary TB and metabolic products of M.
      tuberculosis, principally derivatives of naphthalene, benzene and alkanes. A
      multivariate predictive algorithm identified active pulmonary TB with 80%
      accuracy (area under curve of receiver operating characteristic curve),
      sensitivity=71.2%, and specificity = 72%. Accuracy increased to 84% in age
      matched subgroups. In a population with 5% prevalence, the breath test would
      identify active pulmonary TB with 98% negative predictive value and 13% positive
      predictive value. CONCLUSIONS: A six-minute point-of-care breath test for
      volatile biomarkers accurately identified subjects with active pulmonary TB.

PMID- 22647660
TI  - Individual factors associated with L- and H-type Bovine Spongiform encephalopathy
      in France.
AB  - BACKGROUND: Cattle with L-type (L-BSE) and H-type (H-BSE) atypical Bovine
      Spongiform encephalopathy (BSE) were identified in 2003 in Italy and France
      respectively before being identified in other countries worldwide. As of December
      2011, around 60 atypical BSE cases have currently been reported in 13 countries,
      with over one third in France. While the epidemiology of classical BSE (C-BSE)
      has been widely described, atypical BSEs are still poorly documented, but appear
      to differ from C-BSE. We analysed the epidemiological characteristics of the 12
      cases of L-BSE and 11 cases of H-BSE detected in France from January 2001 to late
      2009 and looked for individual risk factors. As L-BSE cases did not appear to be
      homogeneously distributed throughout the country, two complementary methods were
      used: spatial analysis and regression modelling. L-BSE and H-BSE were studied
      separately as both the biochemical properties of their pathological prion protein
      and their features differ in animal models. RESULTS: The median age at detection
      for L-BSE and H-BSE cases was 12.4 (range 8.4-18.7) and 12.5 (8.3-18.2) years
      respectively, with no significant difference between the two distributions.
      However, this median age differed significantly from that of classical BSE (7.0
      (range 3.5-15.4) years). A significant geographical cluster was detected for L
      BSE. Among animals over eight years of age, we showed that the risk of being
      detected as a L-BSE case increased with age at death. This was not the case for H
      BSE. CONCLUSION: To the best of our knowledge this is the first study to describe
      the epidemiology of the two types of atypical BSE. The geographical cluster
      detected for L-BSE could be partly due to the age structure of the background
      tested bovine population. Our regression analyses, which adjusted for the effect
      of age and birth cohort showed an age effect for L-BSE and the descriptive
      analysis showed a particular age structure in the area where the cluster was
      detected. No birth cohort effect was evident. The relatively small number of
      cases of atypical BSE and the few individual data available for the tested
      population limited our analysis to the investigation of age and cohort effect
      only. We conclude that it is essential to maintain BSE surveillance to further
      elucidate our findings.

PMID- 22647662
TI  - [Who will be the first-born baby boomers at risk of financial vulnerability in
      retirement? A comparison of Quebec and Ontario].
AB  - The oncoming retirement of baby boomers has governments worried. Will individual
      baby boomers demonstrate the ability to prepare financially for their retirement?
      Well-being in retirement depends largely on financial preparedness during working
      life. Those baby boomers who are the most vulnerable at the end of their working
      lives are more likely to become vulnerable during retirement. This study looks at
      the income of the first baby boomers, those born between 1946 and 1956, aged 50
      to 60, according to the 2006 Canadian census. First we establish the socio
      economic categories for which members are most financially vulnerable. Then, we
      estimate how many baby boomers are vulnerable and to what extent. This study's
      preferred approach is an interprovincial comparison between Quebec and Ontario,
      used to analyze individual aspects of baby boomers' financial positions.

PMID- 22647664
TI  - Patient journey: implications for improving and integrating care for older adults
      with chronic obstructive pulmonary disease.
AB  - Many patients, particularly older patients, interact with multiple providers
      while accessing health care services in a variety of different settings over
      extended periods of time. Understanding older patients' experiences of their
      journeys through the health system is critical to improving service integration
      and quality of care. In this study, we have summarized the experiences of four
      patients living with chronic obstructive pulmonary disease as they interacted
      with the health care system over a three-month period following hospital
      discharge. Guided by case study methodology, we gathered data through semi
      structured interviews and patient logs. Three overarching themes - social
      support, system navigation, and access - emerged from the data. Attending to
      provider-patient and provider-provider communication, and to patient social
      support and self-care needs, could improve integration and care outcomes.
      Achieving what patients perceive as an integrated and effective system will
      require time and commitment.

PMID- 22647663
TI  - Exercise training reduces inflammatory mediators in the intestinal tract of
      healthy older adult mice.
AB  - Aging is associated with increased intestinal inflammation and elevated risk of
      chronic diseases including inflammatory bowel diseases and colon cancer; many
      epidemiologic studies show that regular exercise reduces risk. This study
      examined the effects of long-term voluntary exercise on inflammatory mediators
      expressed in the intestine of older (15-16 months), healthy C57BL/6 mice. Animals
      were assigned to four months of freewheel running (WR; n = 20) or to a
      "sedentary" no wheel running (NWR; n = 20) control group. Intestinal lymphocytes
      were harvested and analysed for expression of (1) pro-inflammatory (TNF-alpha, IL
      1beta) and pleiotropic (IL-6) cytokines, and (2) pro-(caspase-3/-7) and anti-(Bcl
      2) apoptotic proteins. Training was confirmed by skeletal muscle enzyme activity;
      stress was assessed by plasma 8-iso-PGF(2alpha) and corticosterone. The WR mice
      had a lower expression of TNF-alpha, caspase-7, and 8-isoprostanes (p < .05)
      compared to sedentary controls, suggesting that long-term exercise may "protect"
      the bowel by reducing inflammatory cytokine and apoptotic protein expression.

PMID- 22647665
TI  - Older adult mistreatment risk screening: contribution to the validation of a
      screening tool in a domestic setting.
AB  - ABSTRACTThe hidden nature of older adult mistreatment renders its detection in
      the domestic setting particularly challenging. A validated screening instrument
      that can provide a systematic assessment of risk factors can facilitate this
      detection. One such instrument, the "expanded Indicators of Abuse" tool, has been
      previously validated in the Hebrew language in a hospital setting. The present
      study has contributed to the validation of the "e-IOA" in an English-speaking
      community setting in Ontario, Canada. It consisted of two phases: (a) a content
      validity review and adaptation of the instrument by experts throughout Ontario,
      and (b) an inter-rater reliability assessment by home visiting nurses. The
      adaptation, the "Mistreatment of Older Adult Risk Factors" tool, offers a
      comprehensive tool for screening in the home setting. This instrument is
      significant to professional practice as practitioners working with older adults
      will be better equipped to assess for risk of mistreatment.

PMID- 22647667
TI  - Coronary artery dissection and left ventricular thrombus.

PMID- 22647668
TI  - Takotsubo cardiomyopathy: pathophysiology and treatment.
AB  - Since it was first described 20 years ago in Japan, takotsubo cardiomyopathy has
      received considerable interest from the medical community around the world,
      particularly in recent years. Although takotsubo cardiomyopathy was originally
      described as a transient, stress-induced dysfunction of the left ventricular
      apex, other morphological subtypes have now been described. The pathogenesis of
      this disorder is likely to be catecholamine mediated myocyte damage and
      microvascular dysfunction; however, a number of possible alternative theories
      have been suggested. These include oxidative stress, transient coronary
      obstruction and oestrogen deficiency, the last explaining the high prevalence of
      takotsubo cardiomyopathy in women. The treatment remains largely supportive;
      however, a number of agents have been implicated in the acute stage and long
      term. Although most of the patients show complete recovery, there is a high risk
      of complications at the initial presentation requiring intense support.

PMID- 22647666
TI  - HTLV-1 modulates the frequency and phenotype of FoxP3+CD4+ T cells in virus
      infected individuals.
AB  - BACKGROUND: HTLV-1 utilizes CD4 T cells as the main host cell and maintains the
      proviral load via clonal proliferation of infected CD4+ T cells. Infection of
      CD4+ T cells by HTLV-1 is therefore thought to play a pivotal role in HTLV-1
      related pathogenicity, including leukemia/lymphoma of CD4+ T cells and chronic
      inflammatory diseases. Recently, it has been reported that a proportion of HTLV-1
      infected CD4+ T cells express FoxP3, a master molecule of regulatory T cells.
      However, crucial questions remain unanswered on the relationship between HTLV-1
      infection and FoxP3 expression. RESULTS: To investigate the effect of HTLV-1
      infection on CD4+ T-cell subsets, we used flow cytometry to analyze the T-cell
      phenotype and HTLV-1 infection in peripheral mononuclear cells (PBMCs) of four
      groups of subjects, including 23 HTLV-1-infected asymptomatic carriers (AC), 10
      patients with HTLV-1 associated myelopathy/tropical spastic paraparesis
      (HAM/TSP), 10 patients with adult T-cell leukemia (ATL), and 10 healthy donors.
      The frequency of FoxP3+ cells in CD4+ T cells in AC with high proviral load and
      patients with HAM/TSP or ATL was higher than that in uninfected individuals. The
      proviral load was positively correlated with the percentage of CD4+ T cells that
      were FoxP3+. The CD4+FoxP3+ T cells, themselves, were frequently infected with
      HTLV-1. We conclude that FoxP3+ T- cells are disproportionately infected with
      HTLV-1 during chronic infection. We next focused on PBMCs of HAM/TSP patients.
      The expression levels of the Treg associated molecules CTLA-4 and GITR were
      decreased in CD4+FoxP3+ T cells. Further we characterized FoxP3+CD4+ T-cell
      subsets by staining CD45RA and FoxP3, which revealed an increase in CD45RA
      FoxP3low non-suppressive T-cells. These findings can reconcile the inflammatory
      phenotype of HAM/TSP with the observed increase in frequency of FoxP3+ cells.
      Finally, we analyzed ATL cells and observed not only a high frequency of FoxP3
      expression but also wide variation in FoxP3 expression level among individual
      cases. CONCLUSIONS: HTLV-1 infection induces an abnormal frequency and phenotype
      of FoxP3+CD4+ T cells.

PMID- 22647669
TI  - Diagnostic utility and factor structure of the PTSD Checklist in older adults.
AB  - BACKGROUND: Little research has examined the diagnostic utility and factor
      structure of commonly used posttraumatic stress disorder (PTSD) assessment
      instruments in older persons. METHODS: A total of 206 adults aged 60 or older
      (mean age = 69 years; range = 60-92), who resided in the Galveston Bay area when
      Hurricane Ike struck in September 2008, completed a computer-assisted telephone
      interview two-five months after this disaster. Using the PTSD Checklist (PCL),
      PTSD symptoms were assessed related both to this disaster and to participants'
      worst lifetime traumatic event. Total PCL scores were compared to PCL-based,
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)
      derived probable diagnoses of PTSD to determine optimal cut scores. Confirmatory
      factor analyses (CFAs) were conducted to evaluate PTSD symptom structure.
      RESULTS: Receiver operating characteristic analyses indicated that a PCL score of
      39 achieved optimal sensitivity and specificity in assessing a PCL-based,
      algorithm-derived DSM-IV diagnosis of worst event-related PTSD; and that a score
      of 37 optimally assessed probable Ike-related PTSD. CFAs revealed that a recently
      proposed five-factor model - comprised of re-experiencing, avoidance, numbing,
      dysphoric arousal, and anxious arousal factors - provided a better fitting
      representation of both worst event- and disaster-related PTSD symptoms than
      alternative models. Current Ike-related anxious arousal symptoms demonstrated a
      significantly stronger association with current generalized anxiety than
      depressive symptoms, thereby supporting the construct validity of this five
      factor model of PTSD symptomatology. CONCLUSIONS: A PCL score of 37 to 39 may
      help identify probable PTSD in older persons. The expression of PTSD symptoms in
      older adults may be best characterized by a recently proposed five-factor model
      with distinct dysphoric arousal and anxious arousal clusters.

PMID- 22647670
TI  - [A 28-years old pregnant woman with systemic lupus erythematosus, proteinuria and
      arterial hypertension].

PMID- 22647672
TI  - Semi-continuous detection of toxic hexavalent chromium using a sulfur-oxidizing
      bacteria biosensor.
AB  - Toxicity testing is becoming a useful tool for environmental risk assessment. A
      biosensor based on the metabolic properties of sulfur-oxidizing bacteria (SOB)
      has been applied for the detection of toxic chemicals in water. The methodology
      exploits the ability of SOB to oxidize elemental sulfur to sulfuric acid under
      aerobic conditions. The reaction results in an increase in electrical
      conductivity (EC) and a decrease in pH. Five hours after Cr(6+) was added to the
      SOB biosensor operated in semi-continuous mode (1 min rapid feeding and 29 min
      batch reaction), a decrease in effluent EC and an increase in pH (from 2-3 to 6)
      were detected due to Cr(6+) toxicity to SOB. The SOB biosensor is simple; it can
      detect toxic levels of Cr(6+) on the order of minutes to hours, a useful time
      scale for early warning detection systems designed to protect the environment
      from further degradation.

PMID- 22647673
TI  - Dynamic mechanical relaxation and loss in the incommensurate phase of quartz.
AB  - The dynamic mechanical properties of quartz have been studied as a function of
      temperature across the alpha-beta phase transition and in the vicinity of the
      incommensurate (IC) phase on cooling from the beta phase. The mechanical response
      of the IC phase shows strong anelasticity for measurement of Young's modulus
      (closely related to C(11) in our geometry) with modulated stress driven at 1 Hz.
      The dynamic shear modulus does not show similar strong effects in its imaginary
      component, although a very weak anomaly is barely detectable in the real part of
      the modulus. Our results indicate that the incommensurate microstructures within
      the quartz transition interval are susceptible to dilatational stress with
      relaxation times around 1 s.

PMID- 22647671
TI  - Surrounding greenness and exposure to air pollution during pregnancy: an analysis
      of personal monitoring data.
AB  - BACKGROUND: Green spaces are reported to improve health status, including
      beneficial effects on pregnancy outcomes. Despite the suggestions of air
      pollution-related health benefits of green spaces, there is no available evidence
      on the impact of greenness on personal exposure to air pollution. OBJECTIVES: We
      investigated the association between surrounding greenness and personal exposure
      to air pollution among pregnant women and to explore the potential mechanisms, if
      any, behind this association. METHODS: In total, 65 rounds of sampling were
      carried out for 54 pregnant women who resided in Barcelona during 2008-2009. Each
      round consisted of a 2-day measurement of particulate matter with aerodynamic
      diameter <= 2.5 MUm (PM2.5) and a 1-week measurement of nitric oxides collected
      simultaneously at both the personal and microenvironmental levels. The study
      participants were also asked to fill out a time-microenvironment-activity diary
      during the sampling period. We used satellite retrievals to determine the
      surrounding greenness as the average of Normalized Difference Vegetation Index
      (NDVI) in a buffer of 100 m around each maternal residential address. We
      estimated the impact of surrounding greenness on personal exposure levels, home
      outdoor and home-indoor pollutant levels, and maternal time-activity. RESULTS:
      Higher residential surrounding greenness was associated with lower personal, home
      indoor, and home-outdoor PM2.5 levels, and more time spent at home-outdoor.
      CONCLUSIONS: We found lower levels of personal exposure to air pollution among
      pregnant women residing in greener areas. This finding may be partly explained by
      lower home-indoor pollutant levels and more time spent in less polluted home
      outdoor environment by pregnant women in greener areas.

PMID- 22647674
TI  - Molecular identification and population dynamic of Anisakis pegreffii (Nematoda:
      Anisakidae Dujardin, 1845) isolated from the European anchovy (Engraulis
      encrasicolus L.) in the Adriatic Sea.
AB  - Anchovy Engraulis encrasicolus (L.) is a coastal pelagic and euryhaline species
      that represents the only European species of the family Engraulidae, with a
      widespread distribution. In Croatia, it is marketed fresh, frozen, salted or
      marinated and mainly exported to Italy and Spain, however Anisakis sp. larval
      infection is frequently the reason for border rejection. Since it is known that
      the prevalence and intensity of Anisakis infection varies with fish species,
      fishing area and season, the aim of our study was to identify Anisakis sp.
      parasitizing European anchovy and infer its population dynamic through a 2.5-year
      period. Larvae were found coiled and encysted on the external wall of intestine
      (94%) and reproductive organs (6%), rarely in fillets. Prevalence was 76.1% (95%
      confidence limits 74.51-77.56%), mean abundance 6.59 (bootstrap 95% confidence
      limits 5.81-7.26) and mean intensity 8.67 (bootstrap 95% confidence limits 7.82
      9.35). The partial CO2 mitochondrial DNA sequence of the isolated anisakids
      confirmed clustering of the anchovy parasite within A. pegreffii sister group.
      Parasite population structure showed plasticity inferred by fishing ground,
      sampling year and fish gender and size. Compared to anisakid prevalence/abundance
      in other fish, the European anchovy in the Adriatic Sea represents a moderately
      high-infected paratenic host, although in the Mediterranean and Atlantic waters,
      anchovies have shown strikingly lesser values of prevalence. Since this host
      represents one of the most attractive Mediterranean fisheries products
      traditionally consumed without thermal preparation that in any case would not
      disrupt larval antigenicity and prevent human allergies, and given the high
      prevalence of the anisakid within the host, it is necessary to include anchovy
      into more firm risk assessment frames in order to develop measures that will
      support the safe alimentary production and consumption of seafood.

PMID- 22647675
TI  - Bacterial attachment to immobilized extracellular matrix proteins in vitro.
AB  - Meat surfaces are contaminated with bacteria during slaughter and processing.
      Understanding bacterial attachment properties to specific structures of meat
      could result in more targeted interventions to improve its safety and quality.
      However, the influence of temperatures relevant to abattoir environments on
      bacterial attachment to specific meat structures is not known. In this study, the
      effect of temperature and protein concentration on attachment of 10 Escherichia
      coli and seven Salmonella strains to extracellular matrix (ECM) proteins
      (collagen I, fibronectin, collagen IV and laminin) was measured using crystal
      violet stain and epifluorescence microscopy assays. By crystal violet assay, only
      five of 17 strains showed significant attachment to any ECM protein and only one
      strain attached to all proteins. Strains that attached at all tested temperatures
      (4, 25, 37 degrees C) were E. coli M23Sr and M23 (collagen I); E. coli M23Sr
      (fibronectin); E. coli M23Sr, O157:H12 and M23, (collagen IV); and E. coli M23Sr,
      O157:H12, O78:K80:H1, O26:H11 and M23 (laminin). A higher proportion of strains
      attached to basement membrane proteins (laminin and collagen IV) than to
      interstitial proteins (collagen I and fibronectin). Highest attachment levels
      occurred at 4 degrees C for collagen I and at 25 degrees C for the other three
      proteins. Generally, the attachment levels of Salmonella strains to all ECM
      proteins were lower than for E. coli. No significant effect was found for
      concentration of collagen I, fibronectin and collagen IV, but was for higher
      laminin concentration. A strong positive correlation was found between results of
      both the crystal violet and epifluorescent methods (r>=0.905, p<0.05). This study
      demonstrated that attachment properties to ECM proteins displayed distinct
      variation among strains, that temperature highly influenced attachment and that
      protein concentration had a minor effect.

PMID- 22647676
TI  - Anti-infective bovine colostrum oligosaccharides: Campylobacter jejuni as a case
      study.
AB  - Campylobacter jejuni is the leading cause of acute bacterial infectious diarrhea
      in humans. Unlike in humans, C. jejuni is a commensal within the avian host.
      Heavily colonized chickens often fail to display intestinal disease, and no
      cellular attachment or invasion has been demonstrated in-vivo. Recently,
      researchers have shown that the reason for the attenuation of C. jejuni virulence
      may be attributed to the presence of chicken intestinal mucus and more
      specifically chicken mucin. Since mucins are heavily glycosylated molecules this
      observation would suggest that glycan-based compounds may act as anti-infectives
      against C. jejuni. Considering this, we have investigated naturally sourced foods
      for potential anti-infective glycans. Bovine colostrum rich in neutral and acidic
      oligosaccharides has been identified as a potential source of anti-infective
      glycans. In this study, we tested oligosaccharides isolated and purified from the
      colostrum of Holstein Friesian cows for anti-infective activity against a highly
      invasive strain of C. jejuni. During our initial studies we structurally defined
      37 bovine colostrum oligosaccharides (BCO) by HILIC-HPLC coupled with
      exoglycosidase digests and off-line mass spectroscopy, and demonstrated the
      ability of C. jejuni to bind to some of these structures, in-vitro. We also
      examined the effect of BCO on C. jejuni adhesion to, invasion of and
      translocation of HT-29 cells. BCO dramatically reduced the cellular invasion and
      translocation of C. jejuni, in a concentration dependent manner. Periodate
      treatment of the BCO prior to inhibition studies resulted in a loss of the anti
      infective activity of the glycans suggesting a direct oligosaccharide-bacterial
      interaction. This was confirmed when the BCO completely prevented C. jejuni
      binding to chicken intestinal mucin, in-vitro. This study builds a strong case
      for the inclusion of oligosaccharides sourced from cow's milk in functional
      foods. However, it is only through further understanding the structure and
      function of milk oligosaccharides that such compounds can reach their potential
      as food ingredients.

PMID- 22647677
TI  - Synergistic effect of steam and lactic acid against Escherichia coli O157:H7,
      Salmonella Typhimurium, and Listeria monocytogenes biofilms on polyvinyl chloride
      and stainless steel.
AB  - This study was designed to investigate the individual and combined effects of
      steam and lactic acid (LA) on the inactivation of biofilms formed by Escherichia
      coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes on polyvinyl
      chloride (PVC) and stainless steel. Six day old biofilms were developed on PVC
      and stainless steel coupons by using a mixture of three strains each of three
      foodborne pathogens at 25 degrees C. After biofilm development, PVC and stainless
      steel coupons were treated with LA alone (immersed in 0.5% or 2% for 5s, 15s, and
      30s), steam alone (on both sides for 5, 10, and 20s), and the combination of
      steam and LA. The numbers of biofilm cells of the three foodborne pathogens were
      significantly (p<0.05) reduced as the amount of LA and duration of steam exposure
      increased. There was a synergistic effect of steam and LA on the viability of
      biofilm cells of the three pathogens. For all biofilm cells of the three
      foodborne pathogens, reduction levels of individual treatments ranged from 0.11
      to 2.12 log CFU/coupon. The combination treatment of steam and LA achieved an
      additional 0.2 to 2.11 log reduction compared to the sum of individual
      treatments. After a combined treatment of immersion in 2% LA for 15s or 30s
      followed by exposure to steam for 20s, biofilm cells of the three pathogens were
      reduced to below the detection limit (1.48 log). From the results of this study,
      bacterial populations of biofilms on PVC coupons did not receive the same thermal
      effect as on stainless steel coupons. Effectiveness of steam and LA may be
      attributed to the difference between Gram-negative and Gram-positive
      characteristics of the bacteria studied. The results of this study suggest that
      the combination of steam and LA has potential as a biofilm control intervention
      for food processing facilities.

PMID- 22647678
TI  - What are the key conditions associated with lower limb amputations in a major
      Australian teaching hospital?
AB  - BACKGROUND: Lower extremity amputation results in significant global morbidity
      and mortality. Australia appears to have a paucity of studies investigating lower
      extremity amputation. The primary aim of this retrospective study was to
      investigate key conditions associated with lower extremity amputations in an
      Australian population. Secondary objectives were to determine the influence of
      age and sex on lower extremity amputations, and the reliability of hospital coded
      amputations. METHODS: Lower extremity amputation cases performed at the Princess
      Alexandra Hospital (Brisbane, Australia) between July 2006 and June 2007 were
      identified through the relevant hospital discharge dataset (n = 197). All
      eligible clinical records were interrogated for age, sex, key condition
      associated with amputation, amputation site, first ever amputation status and the
      accuracy of the original hospital coding. Exclusion criteria included records
      unavailable for audit and cases where the key condition was unable to be
      determined. Chi-squared, t-tests, ANOVA and post hoc tests were used to determine
      differences between groups. Kappa statistics were used to measure reliability
      between coded and audited amputations. A minimum significance level of p < 0.05
      was used throughout. RESULTS: One hundred and eighty-six cases were eligible and
      audited. Overall 69% were male, 56% were first amputations, 54% were major
      amputations, and mean age was 62 +/- 16 years. Key conditions associated included
      type 2 diabetes (53%), peripheral arterial disease (non-diabetes) (18%), trauma
      (8%), type 1 diabetes (7%) and malignant tumours (5%). Differences in ages at
      amputation were associated with trauma 36 +/- 10 years, type 1 diabetes 52 +/- 12
      years and type 2 diabetes 67 +/- 10 years (p < 0.01). Reliability of original
      hospital coding was high with Kappa values over 0.8 for all variables.
      CONCLUSIONS: This study, the first in over 20 years to report on all levels of
      lower extremity amputations in Australia, found that people undergoing amputation
      are more likely to be older, male and have diabetes. It is recommended that large
      prospective studies are implemented and national lower extremity amputation rates
      are established to address the large preventable burden of lower extremity
      amputation in Australia.

PMID- 22647679
TI  - HIF1A C1772T polymorphism leads to HIF-1alpha mRNA overexpression in prostate
      cancer patients.
AB  - Hypoxia-inducible factor 1alpha (HIF-1alpha) gene polymorphisms have been
      investigated for a possible role in mediating genetic predisposition to cancer.
      Our previous data show that men homozygous to C1772T polymorphism had 4-fold risk
      to develop prostate cancer. Therefore, we studied the effects of C1772T
      polymorphism on HIF-1alpha expression. HIF-1alpha mRNA expression levels were
      significantly higher in peripheral blood leukocytes of prostate cancer patients
      with the TT genotype compared with the CC genotype. Expression of C1772T HIF
      1alpha in HIF-1alpha knockout cancer cells showed higher expression levels and
      stabilization of HIF-1alpha mRNA compared with the wild-type. Mutated HIF-1alpha
      protein half-life was similar to that of the wild-type. Hence, our data provide
      evidence that C1772T polymorphism causes activation of HIF-1alpha as a gain-of
      function mechanism driven by stabilization of HIF-1alpha mRNA. These findings may
      also explain the increased risk of men homozygous to this mutation to develop
      prostate cancer.

PMID- 22647680
TI  - A dosimetric phantom study of dose accuracy and build-up effects using IMRT and
      RapidArc in stereotactic irradiation of lung tumours.
AB  - BACKGROUND AND PURPOSE: Stereotactic lung radiotherapy (SLRT) has emerged as a
      curative treatment for medically inoperable patients with early-stage non-small
      cell lung cancer (NSCLC) and the use of intensity-modulated radiotherapy (IMRT)
      and volumetric modulated arc treatments (VMAT) have been proposed as the best
      practical approaches for the delivery of SLRT. However, a large number of narrow
      field shapes are needed in the dose delivery of intensity-modulated techniques
      and the probability of underdosing the tumour periphery increases as the
      effective field size is decreased. The purpose of this study was to evaluate
      small lung tumour doses irradiated by intensity-modulated techniques to
      understand the risk for dose calculation errors in precision radiotherapy such as
      SLRT. MATERIALS AND METHODS: The study was executed with two heterogeneous
      phantoms with targets of O1.5 and O4.0 cm. Dose distributions in the simulated
      tumours delivered by small sliding window apertures (SWAs), IMRT and RapidArc
      treatment plans were measured with radiochromic film. Calculation algorithms of
      pencil beam convolution (PBC) and anisotropic analytic algorithm (AAA) were used
      to calculate the corresponding dose distributions. RESULTS: Peripheral doses of
      the tumours were decreased as SWA decreased, which was not modelled by the
      calculation algorithms. The smallest SWA studied was 2 mm, which reduced the 90%
      isodose line width by 4.2 mm with the O4.0 cm tumour as compared to open field
      irradiation. PBC was not able to predict the dose accurately as the gamma
      evaluation failed to meet the criteria of +/-3%/+/-1 mm on average in 61% of the
      defined volume with the smaller tumour. With AAA the corresponding value was 16%.
      The dosimetric inaccuracy of AAA was within +/-3% with the optimized treatment
      plans of IMRT and RapidArc. The exception was the clinical RapidArc plan with
      dose overestimation of 4%. CONCLUSIONS: Overall, the peripheral doses of the
      simulated lung tumours were decreased by decreasing the SWA. To achieve adequate
      surface dose coverage to small lung tumours with a difference less than 1 mm in
      the isodose line radius between the open and modulated field, a larger than 6 mm
      SWA should be used in the dose delivery of SLRT.

PMID- 22647681
TI  - miRNA-101: a potential target for tumor therapy.
AB  - microRNAs are genomically encoded small non-coding RNAs that regulate genetic
      information by controlling stability or translation of mRNAs. Down-regulated
      expression of microRNA-101 (miRNA-101) has been found in a variety of cancers,
      and associated with the invasion and progression of malignancies. Recent advances
      in the understanding of miRNA-101 biogenesis, target recognition and
      participation in regulatory pathways demonstrate a role for miRNA-101 in
      tumorigenesis. miRNA-101 gene therapy is of great potentiality to be a new
      modality for treatment of cancers.

PMID- 22647682
TI  - Risk factor analysis of vasovagal reaction from blood donation.
AB  - BACKGROUND: Vasovagal reaction (VVR) is the most frequent side effect at blood
      collection sites. AIMS: To protect donors, factors contributing to VVR were
      analysed. MATERIALS AND METHODS: Complications following whole blood and
      apheresis donations have been recorded and accumulated by the Japanese Red Cross
      Tokyo Blood Centre. A dataset of 43,948 donors who had no complications was
      prepared as a control by randomly selecting days in each season in the 2006 and
      2007 fiscal years. Factors contributing to 4924 VVR incidents in the 2006 and
      2007 fiscal years were analysed by univariate and multivariate logistic
      regression. RESULTS: The age, weight, body mass index (BMI), predonation systolic
      and diastolic pressure, and circulating blood volume were lower, and the pulse
      was higher, for the VVR group compared to the control group (p<0.0001). The VVR
      group had more female donors, less sleep, and more time since a meal than the
      control. In multivariate analysis, significant risk factors for 400 ml whole
      blood donors, which are the majority of donors, were an age <50 years, being
      female, a BMI <25, pulse >=90/min, sleep duration <8 h, the time after eating >=4
      h, a first time donation and circulating blood volume of <4.3 l. Sleep duration
      of <6 h was shown to be a VVR risk as much as a first time donation. CONCLUSION:
      From our analysis, the amount of sleep obtained the previous night should be
      considered at the reception of donors.

PMID- 22647683
TI  - Survey of current practice for monitoring and management of platelet
      refractoriness in Italy.
AB  - Platelet transfusion failure is a common phenomenon affecting from 7% to 34% of
      haematology-oncology patients. Monitoring the efficacy of platelet transfusion
      through the evaluation of a post-transfusion platelet count and clinical response
      represent an important guide for subsequent transfusions and for the detection of
      refractoriness. The aim of this survey was to investigate physicians' attitudes
      and practices regarding the monitoring of platelet response and the management of
      platelet refractoriness. An e-mail based survey was conducted among the heads of
      blood banks with a hemapheresis ward in Italy. Heads of 64 centers out of the 122
      initially identified (52%) completed the entire survey. Apheresis, buffy-coat
      pool, and platelet rich plasma represented an average of 46%, 38% and 17% of the
      total number of transfusions, respectively. In the prophylaxis of hemorrhagic
      episodes, most of the centers utilized as standard dose one unit of apheresis
      platelets (55.7%) and/or one unit of buffy-coat pool platelets (42.6%), while
      11.4% of respondents used an average of 6 units of platelet rich plasma. In only
      27.9% of the centers was the platelet dose established based on the body weight
      of the recipient. Only one-third of the centers evaluated the response to
      platelet transfusion in all patients, while the rate increased to 60% in onco
      hematological patients. Among patients transfused on an outpatient basis, the
      rate dropped to 20%, and a platelet sample taken 10 min after transfusion was
      generally used. The survey documented a substantial lack of interaction between
      the clinician requesting the transfusion and the one responsible for the
      preparation and delivery of the product, with both figures involved in the
      diagnosis of refractoriness in only one-third of the centers. In conclusion,
      despite being a frequent condition, platelet refractoriness is still managed with
      a high degree of heterogeneity and often overlooked. Better adherence to existing
      guidelines and standard operating procedures, as well as the involvement of
      transfusion centers in prospective evaluations can help reduce this variability
      and improve the outcome of transfused patients.

PMID- 22647684
TI  - A lesson to learn from Hemovigilance: The impact of nurses' transfusion practice
      on mistransfusion.
AB  - INTRODUCTION AND AIM: In recent years, there has been a gradual increase in
      mistransfusion events reported to our Regional Hemovigilance Division. Our
      objective was to design a transfusion practice nursing survey to study the causes
      of the increasing mistransfusion rate. MATERIALS AND METHODS: Mistransfusion
      rates between 2007 and 2009 were obtained from the Balearic Island Hemovigilance
      Division (BIHVD), one of the 17 regional HV divisions in the Spanish
      Hemovigilance network. The BIHVD designed a transfusion practice nursing survey
      to study the causes of the increasing mistransfusion rate. Every year, 614 nurses
      carry out around 47,000 transfusions in our region. Data were collected through
      voluntary, anonymous, questionnaires which included questions about socio
      professional factors, transfusion training and education, together with
      transfusion practice questions both related and unrelated to guidelines and
      nurses' attitudes. Multiple regression analysis was used to investigate which
      mistransfusion prediction factors were most accurate. RESULTS: The survey
      response rate was 363 out of 614 (59.12%). Marked deficits in nurses' education
      and training and low transfusion frequency had a strong negative impact on the
      incidence of transfusion errors (r=-0.70; p=0.01). This is supported by evidence
      that the performance of well-trained nurses who transfused either daily or weekly
      and strictly followed transfusion guidelines was associated with a lower
      mistransfusion rate (r=-0.93; p<0.01). CONCLUSION: Nurses' training, education
      and how frequently a nurse transfuses are the key factors for best transfusion
      practice in our region. This study illustrates the feasibility of using
      Hemovigilance resources to investigate the causes of mistransfusion.

PMID- 22647685
TI  - How do we collect better granulocyte?
AB  - We studied retrospectively the factors affecting the product quality in 459 donor
      granulocyte apheresis procedures from 420 donors for 71 neutropenic patients from
      2004 to 2010 in a single center. The counts of the granulocyte and platelet
      collected were measured to evaluate the product quality. The data was analyzed to
      determine a possible relationship between product quality and several parameters
      including gender, preleukapheresis neutrophil count, type of anticoagulation and
      separator type and mode of the apheresis system. We found that collection of
      better granulocyte is possible from a donor in a single procedure by changing
      anticoagulation type and separator mode during apheresis.

PMID- 22647686
TI  - Clinical and radiological predictors of nipple-areola complex involvement in
      breast cancer patients.
AB  - INTRODUCTION: Nipple-areola sparing mastectomy (NSM) is increasingly used in
      patients with non-locally advanced breast carcinoma. Literature data on the
      preoperative assessment of the nipple-areola complex (NAC) are inconsistent.
      PATIENTS AND METHODS: Out of 1359 patients submitted to total mastectomy between
      2001 and 2010, we selected 61 patients whose pre-operative mammogram (MX) was
      available (MX group) and 39 patients who underwent preoperative breast magnetic
      resonance imaging (magnetic resonance imaging (MRI) group). The rate of NAC
      involvement, the value of MX and MRI to predict NAC involvement and the
      performance of the Schecter's and Loewn's algorithms for the prediction of NAC
      involvement were evaluated. RESULTS: In the combined MX and MRI groups, NAC
      involvement was found in 14% of the cases. At univariate analysis, tumour stage
      (p value: 0.03), central tumour location (p value: 0.004), presence of NAC
      retraction (p value: 0.001) and tumour-NAC distance (p value: 0.006) were
      associated with NAC involvement, but only the latter parameter retained
      statistical significance at multivariate analysis (p value: 0.05). Tumour-NAC
      distance was a key predictor of NAC involvement, with a negative predictive value
      of 94% for MX and of 100% for MRI when the cut-off was set at 10mm. Overall, the
      performance of Schecter's and Loewn's algorithms was respectively lower and
      similar as compared to the original series. CONCLUSIONS: Occult tumour
      involvement of the NAC is detected in a minority of breast cancer patients
      submitted to mastectomy. A tumour-NAC distance >= 10 mm by MRI may help select
      patients candidate to NSM.

PMID- 22647687
TI  - Transforming growth factor-beta1 attenuates junctional adhesion molecule-A and
      contributes to breast cancer cell invasion.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a potent regulator in promoting
      the invasion and proliferation of breast cancer cells. Junctional adhesion
      molecule-A (JAM-A) is a tight junction protein that displays an inverse
      relationship to cell invasiveness in breast cancer cells. Whether TGF-beta1
      signaling induces alteration of JAM-A expression leading to cell invasion has not
      been investigated. In this study, we report that TGF-beta1 down-regulated JAM-A
      expression via its effect on both transcriptional and post-translational
      regulations of JAM-A, thus inducing cell invasion. On exploring whether TGF-beta1
      might be the upstream regulator of JAM-A expression, we found that knockdown of
      TGF-beta receptors and canonical Smad signaling could upregulate JAM-A level and
      inhibit cell invasion in MDA-MB-231 cells. TGF-beta1 treatment of MCF-7 cells
      caused a significant reduction of JAM-A mRNA and protein and induced cell
      invasion. Delineating the signal mechanisms involved in TGF-beta1-mediated JAM-A
      repression, we found that TGF-beta1 significantly inhibited JAM-A gene
      transcription via the activation of Smads. In addition to Smad activation, we
      found that involvement of p54 JNK is crucial for post-translational modification
      of TGF-beta1-mediated JAM-A protein degradation. Blockage of JNK pathway by
      inhibitor could attenuate TGF-beta1-induced cell invasion. We provide evidences
      for the first time that TGF-beta1 induces breast cancer cell invasion via TGF
      beta1-mediated control on JAM-A expression. Identification of JAM-A as a
      downstream target of TGF-beta1 represents a crucial mechanism in cancer
      progression.

PMID- 22647688
TI  - Tumor characteristics and recurrence patterns in triple negative breast cancer: a
      comparison between younger (<65) and elderly (>=65) patients.
AB  - BACKGROUND: In an aging population an increasing number of breast cancers is
      diagnosed in elderly women. Tumor characteristics and patterns of metastasation
      have been extensively elucidated in younger triple negative breast cancer (TNBC)
      patients, but data regarding TNBC in elderly women are missing. The goal of this
      investigation was to compare clinical pathological characteristics of younger and
      elderly TNBC patients in order to assess their relevance for TNBC in an aging
      population. METHODS: Data of TNBC patients diagnosed between 1998 and 2004 were
      retrospectively analyzed by computer based chart information. Baseline tumor
      characteristics, patient demographics and patterns of metastasation were compared
      between younger (<65 years) and elderly (>=65 years) TNBC patients. RESULTS: Out
      of 254 TNBC patients 75.6% were <65 years and 24.4% were >=65 years. Mean tumor
      size, tumor grade and number of positive lymph nodes did not differ significantly
      (p=0.865, 0.115 and 0.442, respectively) between both age groups. Distant
      visceral metastases occurred significantly more often than bone metastases in
      both age groups (p<0.001). Local recurrences, bone and secondary lymph node
      metastases were observed at significantly higher numbers in younger patients
      (p=0.035, 0.025 and 0.041, respectively). Elderly TNBC patients received
      significantly less chemotherapy than younger patients (p<0.001). CONCLUSIONS:
      TNBC of elderly patients is an aggressive breast cancer subtype claiming as much
      attention as TNBC in younger patients, thus warranting chemotherapeutic
      intervention irrespectively of age.

PMID- 22647689
TI  - Applying knowledge-anchored hypothesis discovery methods to advance clinical and
      translational research: the OAMiner project.
AB  - The conduct of clinical and translational research regularly involves the use of
      a variety of heterogeneous and large-scale data resources. Scalable methods for
      the integrative analysis of such resources, particularly when attempting to
      leverage computable domain knowledge in order to generate actionable hypotheses
      in a high-throughput manner, remain an open area of research. In this report, we
      describe both a generalizable design pattern for such integrative knowledge
      anchored hypothesis discovery operations and our experience in applying that
      design pattern in the experimental context of a set of driving research questions
      related to the publicly available Osteoarthritis Initiative data repository. We
      believe that this 'test bed' project and the lessons learned during its execution
      are both generalizable and representative of common clinical and translational
      research paradigms.

PMID- 22647690
TI  - Drug-drug interaction through molecular structure similarity analysis.
AB  - BACKGROUND: Drug-drug interactions (DDIs) are responsible for many serious
      adverse events; their detection is crucial for patient safety but is very
      challenging. Currently, the US Food and Drug Administration and pharmaceutical
      companies are showing great interest in the development of improved tools for
      identifying DDIs. METHODS: We present a new methodology applicable on a large
      scale that identifies novel DDIs based on molecular structural similarity to
      drugs involved in established DDIs. The underlying assumption is that if drug A
      and drug B interact to produce a specific biological effect, then drugs similar
      to drug A (or drug B) are likely to interact with drug B (or drug A) to produce
      the same effect. DrugBank was used as a resource for collecting 9454 established
      DDIs. The structural similarity of all pairs of drugs in DrugBank was computed to
      identify DDI candidates. RESULTS: The methodology was evaluated using as a gold
      standard the interactions retrieved from the initial DrugBank database. Results
      demonstrated an overall sensitivity of 0.68, specificity of 0.96, and precision
      of 0.26. Additionally, the methodology was also evaluated in an independent test
      using the Micromedex/Drugdex database. CONCLUSION: The proposed methodology is
      simple, efficient, allows the investigation of large numbers of drugs, and helps
      highlight the etiology of DDI. A database of 58 403 predicted DDIs with
      structural evidence is provided as an open resource for investigators seeking to
      analyze DDIs.

PMID- 22647691
TI  - Pathogenicity and mucosal transmissibility of the R5-tropic simian/human
      immunodeficiency virus SHIV(AD8) in rhesus macaques: implications for use in
      vaccine studies.
AB  - There is an urgent need to develop new pathogenic R5 simian/human
      immunodeficiency viruses (SHIVs) for the evaluation of candidate anti-HIV
      vaccines in nonhuman primates. Here, we characterize swarm SHIV(AD8) stocks,
      prepared from three infected rhesus macaques with documented immunodeficiency at
      the time of euthanasia, for their capacity to establish durable infections in
      macaques following inoculation by the intravenous (i.v.) or intrarectal (i.r.)
      route. All three viral stocks (SHIV(AD8-CE8J), SHIV(AD8-CK15), and SHIV(AD8
      CL98)) exhibited robust replication in vivo and caused marked depletion of CD4(+)
      T cells affecting both memory and naive CD4(+) T lymphocyte subsets following
      administration by either route. Eleven of 22 macaques inoculated with the new
      SHIV(AD8) stocks were euthanized with clinical symptoms of immunodeficiency and
      evidence of opportunistic infections (Pneumocystis, Candida, and Mycobacterium).
      A single but unique founder virus, also present in the SHIV(AD8-CE8J) swarm
      stock, was transmitted to two animals following a single i.r. inoculation of
      approximately 3 50% animal infectious doses, which is close to the threshold
      required to establish infection in all exposed animals. Because the three new
      SHIV(AD8) viruses are mucosally transmissible, exhibited tier 2 sensitivity to
      anti-HIV-1 neutralizing antibodies, deplete CD4(+) T lymphocytes in vivo, and
      induce AIDS in macaques, they are eminently suitable as challenge viruses in
      vaccine experiments.

PMID- 22647692
TI  - Membrane fusion-mediated autophagy induction enhances morbillivirus cell-to-cell
      spread.
AB  - In the context of viral infections, autophagy induction can be beneficial or
      inhibitory. Within the Paramyxoviridae family, only morbilliviruses have been
      investigated and are reported to induce autophagy. Here we show that
      morbilliviruses rapidly induce autophagy and require this induction for efficient
      cell-to-cell spread. Coexpression of both glycoproteins in cells expressing one
      of the cellular receptors was required for autophagy induction, and LC3 punctum
      formation, indicative of autophagy, was mainly observed in syncytia. A similar
      correlation between syncytium formation and autophagy induction was also observed
      for other paramyxovirus glycoproteins, suggesting that membrane fusion-mediated
      autophagy may be common among paramyxoviruses and possibly other enveloped
      viruses.

PMID- 22647693
TI  - Regulation of virus neutralization and the persistent fraction by TRIM21.
AB  - Despite a central role in immunity, antibody neutralization of virus infection is
      poorly understood. Here we show how the neutralization and persistence of
      adenovirus type 5, a prevalent nonenveloped human virus, are dependent upon the
      intracellular antibody receptor TRIM21. Cells with insufficient amounts of TRIM21
      are readily infected, even at saturating concentrations of neutralizing antibody.
      Conversely, high TRIM21 expression levels decrease the persistent fraction of the
      infecting virus and allows neutralization by as few as 1.6 antibody molecules per
      virus. The direct interaction between TRIM21 and neutralizing antibody is
      essential, as single-point mutations within the TRIM21-binding site in the Fc
      region of a potently neutralizing antibody impair neutralization. However,
      infection at high multiplicity can saturate TRIM21 and overcome neutralization.
      These results provide insight into the mechanism and importance of a newly
      discovered, effector-driven process of antibody neutralization of nonenveloped
      viruses.

PMID- 22647694
TI  - Complementation of the function of glycoprotein H of human herpesvirus 6 variant
      A by glycoprotein H of variant B in the virus life cycle.
AB  - Human herpesvirus 6 (HHV-6) is a T-cell-tropic betaherpesvirus. HHV-6 can be
      classified into two variants, HHV-6 variant A (HHV-6A) and HHV-6B, based on
      genetic, antigenic, and cell tropisms, although the homology of their entire
      genomic sequences is nearly 90%. The HHV-6A glycoprotein complex gH/gL/gQ1/gQ2 is
      a viral ligand that binds to the cellular receptor human CD46. Because gH has
      94.3% amino acid identity between the variants, here we examined whether gH from
      one variant could complement its loss in the other. Recently, we successfully
      reconstituted HHV-6A from its cloned genome in a bacterial artificial chromosome
      (BAC) (rHHV-6ABAC). Using this system, we constructed HHV-6ABAC DNA containing
      the HHV-6B gH (BgH) gene instead of the HHV-6A gH (AgH) gene in Escherichia coli.
      Recombinant HHV-6ABAC expressing BgH (rHHV-6ABAC-BgH) was successfully
      reconstituted. In addition, a monoclonal antibody that blocks HHV-6B but not HHV
      6A infection neutralized rHHV-6ABAC-BgH but not rHHV-6ABAC. These results
      indicate that HHV-6B gH can complement the function of HHV-6A gH in the viral
      infectious cycle.

PMID- 22647696
TI  - Efficient human cytomegalovirus reactivation is maturation dependent in the
      Langerhans dendritic cell lineage and can be studied using a CD14+ experimental
      latency model.
AB  - Studies from a number of laboratories have shown that the myeloid lineage is
      prominent in human cytomegalovirus (HCMV) latency, reactivation, dissemination,
      and pathogenesis. Existing as a latent infection in CD34(+) progenitors and
      circulating CD14(+) monocytes, reactivation is observed upon differentiation to
      mature macrophage or dendritic cell (DC) phenotypes. Langerhans' cells (LCs) are
      a subset of periphery resident DCs that represent a DC population likely to
      encounter HCMV early during primary infection. Furthermore, we have previously
      shown that CD34(+) derived LCs are a site of HCMV reactivation ex vivo.
      Accordingly, we have utilized healthy-donor CD34(+) cells to study latency and
      reactivation of HCMV in LCs. However, the increasing difficulty acquiring healthy
      donor CD34(+) cells--particularly from seropositive donors due to the screening
      regimens used--led us to investigate the use of CD14(+) monocytes to generate
      LCs. We show here that CD14(+) monocytes cultured with transforming growth factor
      beta generate Langerin-positive DCs (MoLCs). Consistent with observations using
      CD34(+) derived LCs, only mature MoLCs were permissive for HCMV infection. The
      lytic infection of mature MoLCs is productive and results in a marked inhibition
      in the capacity of these cells to promote T cell proliferation. Pertinently,
      differentiation of experimentally latent monocytes to the MoLC phenotype promotes
      reactivation in a maturation and interleukin-6 (IL-6)-dependent manner.
      Intriguingly, however, IL-6-mediated effects were restricted to mature LCs, in
      contrast to observations with classical CD14(+) derived DCs. Consequently,
      elucidation of the molecular basis behind the differential response of the two DC
      subsets should further our understanding of the fundamental mechanisms important
      for reactivation.

PMID- 22647698
TI  - A specific domain of the Chikungunya virus E2 protein regulates particle
      formation in human cells: implications for alphavirus vaccine design.
AB  - Virus-like particles (VLPs) can be generated from Chikungunya virus (CHIKV), but
      different strains yield variable quantities of particles. Here, we define the
      genetic basis for these differences and show that amino acid 234 in E2
      substantially affects VLP production. This site is located within the acid
      sensitive region (ASR) known to initiate a major conformational change in E1/E2.
      Selected other mutations in the ASR, or changes in pH, also increased VLP yield.
      These results demonstrate that the ASR of E2 plays an important role in
      regulating particle generation.

PMID- 22647697
TI  - Differential patterns of large tumor antigen-specific immune responsiveness in
      patients with BK polyomavirus-positive prostate cancer or benign prostatic
      hyperplasia.
AB  - The role of the polyomavirus BK (BKV) large tumor antigen (L-Tag) as a target of
      immune response in patients with prostate cancer (PCa) has not been investigated
      thus far. In this study, we comparatively analyzed humoral and cellular L-Tag
      specific responsiveness in age-matched patients bearing PCa or benign prostatic
      hyperplasia, expressing or not expressing BKV L-Tag-specific sequences in their
      tissue specimens, and in non-age-matched healthy individuals. Furthermore,
      results from patients with PCa were correlated to 5-year follow-up clinical data
      focusing on evidence of biochemical recurrence (BR) after surgery (prostate
      specific antigen level of >=0.2 ng/ml). In peripheral blood mononuclear cells
      (PBMC) from patients with PCa with evidence of BR and BKV L-Tag-positive tumors,
      stimulation with peptides derived from the BKV L-Tag but not those derived from
      Epstein-Barr virus, influenza virus, or cytomegalovirus induced a peculiar
      cytokine gene expression profile, characterized by high expression of interleukin
      10 (IL-10) and transforming growth factor beta1 and low expression of gamma
      interferon genes. This pattern was confirmed by protein secretion data and
      correlated with high levels of anti-BKV L-Tag IgG. Furthermore, in PBMC from
      these PCa-bearing patients, L-Tag-derived peptides significantly expanded an IL
      10-secreting CD4(+) CD25(+(high)) CD127(-) FoxP3(+) T cell population with an
      effector memory phenotype (CD103(+)) capable of inhibiting proliferation of
      autologous anti-CD3/CD28-triggered CD4(+) CD25(-) T cells. Collectively, our
      findings indicate that potentially tolerogenic features of L-Tag-specific immune
      response are significantly associated with tumor progression in patients with
      BKV(+) PCa.

PMID- 22647699
TI  - Inhibiting early-stage events in HIV-1 replication by small-molecule targeting of
      the HIV-1 capsid.
AB  - The HIV-1 capsid (CA) protein plays essential roles in both early and late stages
      of virl replication and has emerged as a novel drug target. We report hybrid
      structure-based virtual screening to identify small molecules with the potential
      to interact with the N-terminal domain (NTD) of HIV-1 CA and disrupt early,
      preintegration steps of the HIV-1 replication cycle. The small molecule 4,4'
      [dibenzo[b,d]furan-2,8-diylbis(5-phenyl-1H-imidazole-4,2-diyl)]dibenzoic acid
      (CK026), which had anti-HIV-1 activity in single- and multiple-round infections
      but failed to inhibit viral replication in peripheral blood mononuclear cells
      (PBMCs), was identified. Three analogues of CK026 with reduced size and better
      drug-like properties were synthesized and assessed. Compound I-XW-053 (4-(4,5
      diphenyl-1H-imidazol-2-yl)benzoic acid) retained all of the antiviral activity of
      the parental compound and inhibited the replication of a diverse panel of primary
      HIV-1 isolates in PBMCs, while displaying no appreciable cytotoxicity. This
      antiviral activity was specific to HIV-1, as I-XW-053 displayed no effect on the
      replication of SIV or against a panel of nonretroviruses. Direct interaction of I
      XW-053 was quantified with wild-type and mutant CA protein using surface plasmon
      resonance and isothermal titration calorimetry. Mutation of Ile37 and Arg173,
      which are required for interaction with compound I-XW-053, crippled the virus at
      an early, preintegration step. Using quantitative PCR, we demonstrated that
      treatment with I-XW-053 inhibited HIV-1 reverse transcription in multiple cell
      types, indirectly pointing to dysfunction in the uncoating process. In summary,
      we have identified a CA-specific compound that targets and inhibits a novel
      region in the NTD-NTD interface, affects uncoating, and possesses broad-spectrum
      anti-HIV-1 activity.

PMID- 22647700
TI  - Suppression of transcription factor early growth response 1 reduces herpes
      simplex virus 1-induced corneal disease in mice.
AB  - Herpes simplex virus 1 replication initiates angiogenesis and inflammation in the
      cornea. This can result in herpetic stromal keratitis (HSK), which is a leading
      cause of infection-induced corneal blindness. Host cellular factors mediate the
      progression of HSK, but little is known about these cellular factors and their
      mechanisms of action. We show here that the expression of the cellular
      transcription factor early growth response 1 (Egr-1) in HSV-1-infected mouse
      corneas was enhanced. Enhanced Egr-1 expression aggravated HSK by increasing
      viral replication and subsequent neovascularization with high levels of potent
      angiogenic factors, fibroblast growth factor 2, and vascular endothelial growth
      factor. Furthermore, Egr-1 deficiency due to a targeted disruption of the gene or
      knockdown of Egr-1 expression topically using a DNA-based enzyme significantly
      reduced HSK by decreasing both viral replication and the angiogenic response. The
      present study provides the first evidence that endogenous Egr-1 aggravates HSK
      and that blocking Egr-1 reduces corneal damage.

PMID- 22647701
TI  - Marek's disease viral interleukin-8 promotes lymphoma formation through targeted
      recruitment of B cells and CD4+ CD25+ T cells.
AB  - Marek's disease virus (MDV) is a cell-associated and highly oncogenic
      alphaherpesvirus that infects chickens. During lytic and latent MDV infection, a
      CXC chemokine termed viral interleukin-8 (vIL-8) is expressed. Deletion of the
      entire vIL-8 open reading frame (ORF) was shown to severely impair disease
      progression and tumor development; however, it was unclear whether this phenotype
      was due to loss of secreted vIL-8 or of splice variants that fuse exons II and
      III of vIL-8 to certain upstream open reading frames, including the viral
      oncoprotein Meq. To specifically examine the role of secreted vIL-8 in MDV
      pathogenesis, we constructed a recombinant virus, vDeltaMetvIL-8, in which we
      deleted the native start codon from the signal peptide encoding exon I. This
      mutant lacked secreted vIL-8 but did not affect Meq-vIL-8 splice variants. Loss
      of secreted vIL-8 resulted in highly reduced disease and tumor incidence in
      animals infected with vDeltaMetvIL-8 by the intra-abdominal route. Although
      vDeltaMetvIL-8 was still able to spread to naive animals by the natural route,
      infection and lymphomagenesis in contact animals were severely impaired. In vitro
      assays showed that purified recombinant vIL-8 efficiently binds to and induces
      chemotaxis of B cells, which are the main target for lytic MDV replication, and
      also interacts with CD4(+) CD25(+) T cells, known targets of MDV transformation.
      Our data provide evidence that vIL-8 attracts B and CD4(+) CD25(+) T cells to
      recruit targets for both lytic and latent infection.

PMID- 22647703
TI  - Influenza A viruses control expression of proviral human p53 isoforms p53beta and
      Delta133p53alpha.
AB  - Previous studies have described the role of p53 isoforms, including p53beta and
      Delta133p53alpha, in the modulation of the activity of full-length p53, which
      regulates cell fate. In the context of influenza virus infection, an interplay
      between influenza viruses and p53 has been described, with p53 being involved in
      the antiviral response. However, the role of physiological p53 isoforms has never
      been explored in this context. Here, we demonstrate that p53 isoforms play a role
      in influenza A virus infection by using silencing and transient expression
      strategies in human lung epithelial cells. In addition, with the help of a panel
      of different influenza viruses from different subtypes, we also show that
      infection differentially regulates the expressions of p53beta and
      Delta133p53alpha. Altogether, our results highlight the role of p53 isoforms in
      the viral cycle of influenza A viruses, with p53beta and Delta133p53alpha acting
      as regulators of viral production in a p53-dependent manner.

PMID- 22647702
TI  - Genome-wide patterns of intrahuman dengue virus diversity reveal associations
      with viral phylogenetic clade and interhost diversity.
AB  - Analogous to observations in RNA viruses such as human immunodeficiency virus,
      genetic variation associated with intrahost dengue virus (DENV) populations has
      been postulated to influence viral fitness and disease pathogenesis. Previous
      attempts to investigate intrahost genetic variation in DENV characterized only a
      few viral genes or a limited number of full-length genomes. We developed a whole
      genome amplification approach coupled with deep sequencing to capture intrahost
      diversity across the entire coding region of DENV-2. Using this approach, we
      sequenced DENV-2 genomes from the serum of 22 Nicaraguan individuals with
      secondary DENV infection and captured ~75% of the DENV genome in each sample
      (range, 40 to 98%). We identified and quantified variants using a highly
      sensitive and specific method and determined that the extent of diversity was
      considerably lower than previous estimates. Significant differences in intrahost
      diversity were detected between genes and also between antigenically distinct
      domains of the Envelope gene. Interestingly, a strong association was discerned
      between the extent of intrahost diversity in a few genes and viral clade
      identity. Additionally, the abundance of viral variants within a host, as well as
      the impact of viral mutations on amino acid encoding and predicted protein
      function, determined whether intrahost variants were observed at the interhost
      level in circulating Nicaraguan DENV-2 populations, strongly suggestive of
      purifying selection across transmission events. Our data illustrate the value of
      high-coverage genome-wide analysis of intrahost diversity for high-resolution
      mapping of the relationship between intrahost diversity and clinical,
      epidemiological, and virological parameters of viral infection.

PMID- 22647705
TI  - Disability and supported employment:  impact on employment, income, and
      allowances.
AB  - In this article, we examine supported employment and its impact on the level of
      employment, disposable income, and sum of allowances, targeting a group of
      individuals with disabilities. We have particularly focused on individuals with
      psychiatric disabilities. Supported employment is a vocational rehabilitation
      service with an empowerment approach that has competitive employment as an
      expressed goal. Data collected from two Swedish organizations, providing services
      based on supported employment, have been used. Two groups have been considered:
      one group focusing on individuals who have received vocational rehabilitation,
      according to the supported employment approach, and the other group focusing on
      individuals who declined supported employment (control group). The groups have
      been examined according to a 'before-and-after the intervention' design. Outcome
      measures have been retrospectively analyzed. The results indicate that the
      individuals who received supported employment were hired faster, earned a higher
      disposable income, and at the same time, had lower individual allowances. The
      same pattern as that for the overall population emerged for individuals with
      psychiatric disorders. Vocational rehabilitation based on the principles of
      supported employment may be very effective for individuals to gain employment, a
      better disposable income, and a substantial cutback in allowances. The
      intervention should be tailored according to individual needs rather than
      organizational rules.

PMID- 22647704
TI  - Vpu-deficient HIV strains stimulate innate immune signaling responses in target
      cells.
AB  - Acute virus infection induces a cell-intrinsic innate immune response comprising
      our first line of immunity to limit virus replication and spread, but viruses
      have developed strategies to overcome these defenses. HIV-1 is a major public
      health problem; however, the virus-host interactions that regulate innate immune
      defenses against HIV-1 are not fully defined. We have recently identified the
      viral protein Vpu to be a key determinant responsible for HIV-1 targeting and
      degradation of interferon regulatory factor 3 (IRF3), a central transcription
      factor driving host cell innate immunity. IRF3 plays a major role in pathogen
      recognition receptor (PRR) signaling of innate immunity to drive the expression
      of type I interferon (IFN) and interferon-stimulated genes (ISGs), including a
      variety of HIV restriction factors, that serve to limit viral replication
      directly and/or program adaptive immunity. Here we interrogate the cellular
      responses to target cell infection with Vpu-deficient HIV-1 strains. Remarkably,
      in the absence of Vpu, HIV-1 triggers a potent intracellular innate immune
      response that suppresses infection. Thus, HIV-1 can be recognized by PRRs within
      the host cell to trigger an innate immune response, and this response is unmasked
      only in the absence of Vpu. Vpu modulation of IRF3 therefore prevents virus
      induction of specific innate defense programs that could otherwise limit
      infection. These observations show that HIV-1 can indeed be recognized as a
      pathogen in infected cells and provide a novel and effective platform for
      defining the native innate immune programs of target cells of HIV-1 infection.

PMID- 22647706
TI  - Significance of physical weathering of two-texturally different soils for the
      saturated transport of Escherichia coli and bromide.
AB  - This study was carried out to investigate the transport of Escherichia coli NAR
      and bromide (Br) through repacked (R) and weathered (W) soil columns. A
      suspension containing E. coli NAR and Br were leached and the effluent from the
      weathered soil columns had greater contaminant concentrations than that from the
      repacked soil columns. The time to the concentration peak of (C(max)) E. coli NAR
      and Br increased in the order CL-W < SL-W < SL-R < CL-R. The breakthrough
      sequence suggests the formation of a heterogeneous soil pore network induced by
      weathering and the importance of accelerated flow in the weathered columns. The
      dual-permeability model in HYDRUS-1D software was used to simulate the E. coli
      NAR and Br transport parameters by inverse modeling. Parameters of the attachment
      detachment model were calculated using the dual-permeability model parameters
      fitted to the BTCs of E. coli NAR. A greater attachment coefficient associated
      with soil repacking and the finer textured clayey soil demonstrated the
      importance of adsorbent site and smaller pore spacing in these treatments.
      Smaller attachment and adsorption isotherm coefficients in weathered soil columns
      suggest the need for further research to validate this as a predictive model for
      the risks for vadose zone contaminant transport.

PMID- 22647707
TI  - Hexabromocyclododecane (HBCD) stereoisomers in U.S. food from Dallas, Texas.
AB  - BACKGROUND: Hexabromocyclododecane (HBCD) is a brominated flame retardant used in
      polystyrene foams in thermal insulation and electrical equipment. The HBCD
      commercial mixture consists mainly of alpha, beta, and gamma stereoisomers.
      Health concerns of HBCD exposure include alterations in immune and reproductive
      systems, neurotoxic effects, and endocrine disruption. Stereoisomer-specific
      levels of HBCD have not been measured previously in U.S. food. OBJECTIVES: We
      measured HBCD stereoisomer levels in U.S. foods from Dallas, Texas, supermarkets.
      METHODS: Convenience samples of commonly consumed foods were purchased from
      supermarkets in Dallas in 2009-2010. Food samples included a wide variety of
      lipid-rich foods: fish, peanut butter, poultry, pork, and beef. Thirty-six
      individual food samples were collected in 2010 and analyzed for alpha-, beta-,
      and gamma-HBCD stereoisomers using liquid chromatography-tandem mass spectrometry
      (LC-MS/MS). Ten pooled food samples previously collected in 2009 for a study of
      total HBCD levels using gas chromatography-mass spectrometry (GC-MS), were
      reanalyzed for alpha-, beta-, and gamma-HBCD stereoisomers using LC-MS/MS.
      RESULTS: Of the 36 measured individual foods, 15 (42%) had detectable levels of
      HBCD. Median (ranges) of alpha- and gamma-HBCD concentrations were 0.003 (< 0.005
      1.307) and 0.005 (< 0.010-0.143) ng/g wet weight (ww), respectively; beta-HBCD
      was present in three samples with a median (range) of 0.003 (< 0.005-0.019) ng/g
      ww. Median levels (range) for alpha-, beta-, and gamma-HBCD, in pooled samples
      were 0.077 (0.010-0.310), 0.008 (< 0.002-0.070), and 0.024 (0.012-0.170) ng/g ww,
      respectively. CONCLUSIONS: alpha-HBCD was detected most frequently and at highest
      concentrations, followed by gamma-, and then beta-HBCD, in food samples from
      Dallas, Texas. Food may be a substantial contributor to the elevated alpha-HBCD
      levels observed in humans. These data suggest that larger and more representative
      sampling should be conducted.

PMID- 22647708
TI  - Normal early pregnancy: a transient state of epigenetic change favoring
      hypomethylation.
AB  - The objective of this study was to analyze genome-wide differential methylation
      patterns in maternal leukocyte DNA in early pregnant and non-pregnant states.
      This is an age and body mass index matched case-control study comparing the
      methylation patterns of 27,578 cytosine-guanine (CpG) sites in 14,495 genes in
      maternal leukocyte DNA in early pregnancy (n = 14), in the same women postpartum
      (n = 14), and in nulligravid women (n = 14) on a BeadChip platform. Transient
      widespread hypomethylation was found in early pregnancy as compared with the non
      pregnant states. Methylation of nine genes was significantly different in early
      pregnancy compared with both postpartum and nulligravid states (< 10% False
      Discovery Rate). Early pregnancy may be characterized by widespread
      hypomethylation compared with non-pregnant states; there is no apparent permanent
      methylation imprint after a normal term gestation. Nine potential candidate genes
      were identified as differentially methylated in early pregnancy and may play a
      role in the maternal adaptation to pregnancy.

PMID- 22647709
TI  - Impact of a model synovial fluid on supported lipid membranes.
AB  - The interaction of a model synovial fluid, here a solution of 3mg/mL hyaluronic
      acid (HA) in heavy water (D(2)O), with an oligolamellar stack of lipid (DMPC)
      membranes on silicon support has been studied by neutron reflectometry and
      infrared spectroscopy on the molecular scale at non-physiological and
      physiological conditions. The system under investigation represents a simple
      model for lipid-coated mammalian joints and other artificial implant surfaces.
      When exposed to pure D(2)O at 21 degrees C, i.e. below the main phase transition
      of the system, the lipid membranes show a lamellar spacing of 65A. Heating to 26
      degrees C results in detachment of all lipid bilayers except for the innermost
      lipid lamella directly adsorbed to the surface of the silicon support. On the
      contrary, when incubated in the solution of HA in D(2)O the oligolamellar lipid
      system starts swelling. In addition, heating to 39 degrees C does not result in
      loss of the lipid membranes into the liquid phase. The interfacial lipid coating
      adopts a new stable lamellar state with an increase in d-spacing by 380% to 247A
      measured after 43 days of incubation with the model synovial fluid. Potential
      consequences for joint lubrication and protective wear functionality are
      considered.

PMID- 22647710
TI  - Summary of notifiable diseases--United States, 2010.
AB  - The Summary of Notifiable Diseases United States, 2010 contains the official
      statistics, in tabular and graphic form, for the reported occurrence of
      nationally notifiable infectious diseases in the United States for 2010. Unless
      otherwise noted, the data are final totals for 2010, reported as of June 30,
      2011. These statistics are collected and compiled from reports sent by state
      health departments and territories to the National Notifiable Diseases
      Surveillance System (NNDSS), which is operated by CDC in collaboration with the
      Council of State and Territorial Epidemiologists (CSTE). The Summary is available
      at http:// www.cdc.gov/mmwr/mmwr_su/mmwr_nd/. This site also includes Summary
      publications from previous years.

PMID- 22647711
TI  - The role of cystatins in tick physiology and blood feeding.
AB  - Ticks, as obligate hematophagous ectoparasites, impact greatly on animal and
      human health because they transmit various pathogens worldwide. Over the last
      decade, several cystatins from different hard and soft ticks were identified and
      biochemically analyzed for their role in the physiology and blood feeding
      lifestyle of ticks. All these cystatins are potent inhibitors of papain-like
      cysteine proteases, but not of legumain. Tick cystatins were either detected in
      the salivary glands and/or the midgut, key tick organs responsible for blood
      digestion and the expression of pharmacologically potent salivary proteins for
      blood feeding. For example, the transcription of two cystatins named HlSC-1 and
      Sialostatin L2 was highly upregulated in these tick tissues during feeding.
      Vaccinating hosts against Sialostatin L2 and Om-cystatin 2 as well as silencing
      of a cystatin gene from Amblyomma americanum significantly inhibited the feeding
      ability of ticks. Additionally, Om-cystatin 2 and Sialostatin L possessed strong
      host immunosuppressive properties by inhibiting dendritic cell maturation due to
      their interaction with cathepsin S. These two cystatins, together with
      Sialostatin L2 are the first tick cystatins with resolved three-dimensional
      structure. Sialostatin L, furthermore, showed preventive properties against
      autoimmune diseases. In the case of the cystatin Hlcyst-2, experimental evidence
      showed its role in tick innate immunity, since increased Hlcyst-2 transcript
      levels were detected in Babesia gibsoni-infected larval ticks and the protein
      inhibited Babesia growth. Other cystatins, such as Hlcyst-1 or Om-cystatin 2 are
      assumed to be involved in regulating blood digestion. Only for Bmcystatin was a
      role in tick embryogenesis suggested. Finally, all the biochemically analyzed
      tick cystatins are powerful protease inhibitors, and some may be novel antigens
      for developing anti-tick vaccines and drugs of medical importance due to their
      stringent target specificity.

PMID- 22647712
TI  - Characterization of the tick-pathogen interface by quantitative proteomics.
AB  - Ticks are vectors of pathogens that affect human and animal health worldwide.
      Ticks and the pathogens they transmit have co-evolved molecular interactions
      involving genetic traits of both the tick and the pathogen that mediate their
      development and survival. Proteomics and genomics studies of infected ticks are
      required to understand tick-pathogen interactions and identify potential vaccine
      antigens to control tick infestations and pathogen transmission. In this paper,
      the application of quantitative proteomics to characterize differential protein
      expression in ticks and cultured tick cells in response to pathogen infection is
      reviewed. Analyses using (a) two-dimensional differential in gel electrophoresis
      (DIGE) labeling and (b) protein one-step in gel digestion, peptide iTRAQ
      labeling, and isoelectric focusing fractionation, both followed by peptide and
      protein identifications by mass spectrometry resulted in the identification of
      host, pathogen, and tick proteins differentially expressed in response to
      infection. Although at its infancy, these results showed that quantitative
      proteomics is a powerful approach to characterize the tick-pathogen interface and
      demonstrated pathogen and tick-specific differences in protein expression in
      ticks and cultured tick cells in response to pathogen infection.

PMID- 22647714
TI  - Fluorescence dynamics and fine structure of dark excitons in semiconducting
      single-wall carbon nanotubes.
AB  - Exact diagonalization results are reported for the bright and dark exciton
      structure of semiconducting single-wall carbon nanotubes in the framework of the
      Hubbard model combined with a small crystal approach for several values of the
      correlation coupling strength U/t. Our findings, in the low-intermediate
      correlation regime (1.5 < U/t < 2.1), show the presence of dark states above and
      below the first bright exciton |B> and can account for reported experimental
      values of deep triplet states below |B> and of a K-momentum singlet dark exciton
      above this state. In order to fit the temporal profile of the photoluminescence
      (PL) decay, a bottleneck mechanism is considered involving a few dark states,
      with the respective energy gaps correspondingly obtained in the above-mentioned
      correlation range. We find that a kinetic model with one dark state above and two
      below |B> is able to recover the observed biexponential features of the PL
      behaviour with a reasonable set of parameters. Within this model we attribute the
      long tail of the PL to a delayed luminescence process of the bright state caused
      by the nearby calculated dark states.

PMID- 22647713
TI  - LRRK2 knockout mice have an intact dopaminergic system but display alterations in
      exploratory and motor co-ordination behaviors.
AB  - Mutations in the LRRK2 gene are the most common cause of genetic Parkinson's
      disease. Although the mechanisms behind the pathogenic effects of LRRK2 mutations
      are still not clear, data emerging from in vitro and in vivo models suggests
      roles in regulating neuronal polarity, neurotransmission, membrane and
      cytoskeletal dynamics and protein degradation.We created mice lacking exon 41
      that encodes the activation hinge of the kinase domain of LRRK2. We have
      performed a comprehensive analysis of these mice up to 20 months of age,
      including evaluation of dopamine storage, release, uptake and synthesis,
      behavioral testing, dendritic spine and proliferation/neurogenesis analysis.Our
      results show that the dopaminergic system was not functionally comprised in LRRK2
      knockout mice. However, LRRK2 knockout mice displayed abnormal exploratory
      activity in the open-field test. Moreover, LRRK2 knockout mice stayed longer than
      their wild type littermates on the accelerated rod during rotarod testing.
      Finally, we confirm that loss of LRRK2 caused degeneration in the kidney,
      accompanied by a progressive enhancement of autophagic activity and accumulation
      of autofluorescent material, but without evidence of biphasic changes.

PMID- 22647716
TI  - Homozygous deletion of an 80 kb region comprising part of DNAJC6 and LEPR genes
      on chromosome 1P31.3 is associated with early onset obesity, mental retardation
      and epilepsy.
AB  - CONTEXT: The genomic organization of the LEPR gene is complex and generates three
      independent transcripts whose respective functions are still poorly understood.
      METHODS/RESULTS: We describe here a 7-year old patient with a homozygous 80 kb
      deletion in the chromosomal 1p31.3 region with early onset obesity, mental
      retardation and epilepsy. The deleted region comprises the proximal promoter and
      exons 1 and 2 of the LEPR gene and exons 5 to 19 of the DNAJC6 gene. The deletion
      leads to the deficiency of all canonical OB-R isoforms but maintains the B219 OB
      R short isoforms controlled by the preserved second LEPR promoter. The DNAJC6
      gene encodes auxilin-1, a protein required for clathrin-dependent recycling of
      synaptic vesicles in neurons that is possibly at the origin of the mental
      retardation and epilepsy phenotype. The obese phenotype and the absence of
      signaling-competent OB-R are consistent with previously reported individuals with
      OB-R deficiency. The deletion eliminates an additional transcript of the LEPR
      gene that encodes endospanin-1, a protein that has been genetically and
      biochemically linked to OB-R function. CONCLUSIONS: Our study confirms the
      phenotype of individuals with OB-R deficiency and postulates the effects of
      auxilin-1 deficiency (mental retardation/epilepsy) and endospanin-1 deficiency
      (OB-R specific functions) in humans.

PMID- 22647717
TI  - Protease inhibitors for the treatment of chronic hepatitis C genotype-1
      infection: the new standard of care.
AB  - For the past decade, the standard treatment for chronic hepatitis C infection has
      been pegylated-interferon plus ribavirin. With US Food and Drug Administration
      approval of boceprevir and telaprevir--two protease inhibitors--the standard-of
      care treatment for genotype-1 infection, the main genotype worldwide, is now
      peginterferon plus ribavirin and a protease inhibitor. Rates of sustained
      virological response or cure with triple combination treatment have improved
      substantially, both in patients who have had previous treatment and in those who
      have not. Improvements have been most substantial in populations regarded as
      difficult to treat, such as individuals with cirrhosis. However, despite improved
      response rates, protease inhibitors have incremental toxic effects, high costs,
      increased pill burden, and many drug interactions. Moreover, because new
      antiviral drugs directly inhibit hepatitis C virus, viral resistance has become
      an important issue, essentially precluding use of protease inhibitor monotherapy,
      and potentially restricting future treatment options for patients who
      consequently do not achieve sustained virological response. Protease inhibitors
      are the first of many antiviral medications that will probably be combined in
      future interferon-free regimens.

PMID- 22647718
TI  - Brief report: Relationships between physical activity and depressive symptoms in
      adolescent girls.
AB  - This study examined the relationships between changes in physical activity and
      depressive symptoms in adolescent girls. Participants were 277 urban adolescent
      girls. Physical activity was measured using the 3-Day Physical Activity Recall
      and depressive symptoms were assessed using questionnaire. Data were collected on
      three occasions over a 3-year period. The results of latent growth modelling
      indicated that initial level and change in physical activity was inversely
      associated with initial status and change in depressive symptoms The associations
      were independent of body mass index. Our results encourage the design of
      interventions that reduce depressive symptoms and increase physical activity of
      early adolescent girls.

PMID- 22647715
TI  - Alpha-synuclein aggregation involves a bafilomycin A 1-sensitive autophagy
      pathway.
AB  - Synucleinopathies like Parkinson disease and dementia with Lewy bodies (DLB) are
      characterized by alpha-synuclein aggregates within neurons (Lewy bodies) and
      their processes (Lewy neurites). Whereas alpha-synuclein has been genetically
      linked to the disease process, the pathological relevance of alpha-synuclein
      aggregates is still debated. Impaired degradation is considered to result in
      aggregation of alpha-synuclein. In addition to the ubiquitin-proteasome
      degradation, the autophagy-lysosomal pathway (ALP) is involved in intracellular
      degradation processes for alpha-synuclein. Here, we asked if modulation of ALP
      affects alpha-synuclein aggregation and toxicity. We have identified an induction
      of the ALP markers LAMP-2A and LC3-II in human brain tissue from DLB patients, in
      a transgenic mouse model of synucleinopathy, and in a cell culture model for
      alpha-synuclein aggregation. ALP inhibition using bafilomycin A 1 (BafA1)
      significantly potentiates toxicity of aggregated alpha-synuclein species in
      transgenic mice and in cell culture. Surprisingly, increased toxicity is
      paralleled by reduced aggregation in both in vivo and in vitro models. The
      dichotomy of effects on aggregating and nonaggregating species of alpha-synuclein
      was specifically sensitive to BafA1 and could not be reproduced by other ALP
      inhibitors. The present study expands on the accumulating evidence regarding the
      function of ALP for alpha-synuclein degradation by isolating an aggregation
      specific, BafA1-sensitive, ALP-related pathway. Our data also suggest that
      protein aggregation may represent a detoxifying event rather than being causal
      for cellular toxicity.

PMID- 22647719
TI  - Bioactive briarane diterpenoids from the South China Sea gorgonian Dichotella
      gemmacea.
AB  - Six new briarane diterpenoids, gemmacolides T-Y (1-6), were isolated together
      with three known analogs, juncenolide J (7), praelolide (8), and junceellolide C
      (9), from the South China Sea gorgonian Dichotella gemmacea. The structures of
      the new compounds were elucidated by detailed spectroscopic analysis and
      comparison with reported data. The absolute configuration was suggested based on
      biosynthetic considerations. In an in vitro bioassay, compounds 3 and 6 showed
      potent growth inhibition towards tumor cell lines of A549 and MG63, being
      stronger than the positive control of adriamycin. These compounds also exhibited
      weak antimicrobial activity against the bacterium Escherichia coli and the fungi
      Microbotryum violaceum and Septoria tritici.

PMID- 22647720
TI  - Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2
      c]pyridine derivatives against melanoma cell lines. Part 2.
AB  - A new series of diarylureas and diarylamides possessing 1H-pyrrolo[3,2-c]pyridine
      scaffold was designed and synthesized. Their in vitro antiproliferative
      activities against A375P human melanoma cell line and NCI-9 human melanoma cell
      line panel were tested. All the target compounds, except three amino derivatives
      8g, h and 9h, demonstrated superior potencies against A375P to Sorafenib. In
      addition, compounds 8a and 9b-f demonstrated higher potencies than Vemurafenib
      against A375P. Compounds 8c and 9b were 7.50 and 454.90 times, respectively, more
      selective towards A375P melanoma cells over NIH3T3 fibroblasts. Furthermore,
      compounds 8d, e and 9a-d, f demonstrated very high potencies against the nine
      tested melanoma cell lines at the NCI. The bisamide derivatives 9a-c, f showed 2
      digit nanomolar IC(50) values over different cell lines of the NCI-9 melanoma
      cell lines.

PMID- 22647721
TI  - Synthesis and evaluation of pyridylbenzofuran, pyridylbenzothiazole and
      pyridylbenzoxazole derivatives as 18F-PET imaging agents for beta-amyloid
      plaques.
AB  - The synthesis and SAR of new beta-amyloid binding agents are reported. Evaluation
      of important properties for achieving good signal-to-background ratio is
      described. Compounds 27, 33, and 36 displayed desirable lipophilic and
      pharmacokinetic properties. Compound 27 was further evaluated with
      autoradiographic studies in vitro on human brain tissue and in vivo in Tg2576
      mice. Compound 27 showed an increased signal-to-background ratio compared to
      flutemetamol 4, indicating its suitability as PET ligand for beta-amyloid
      deposits in AD patients. The preparation of the corresponding (18)F-labeled PET
      radioligand of compound 27 is presented.

PMID- 22647722
TI  - Lipase-catalyzed preparation of chromomycin A3 analogues and biological
      evaluation for anticancer activity.
AB  - Several acyl derivatives of the aureolic acid chromomycin A(3) were obtained via
      lipase-catalyzed acylation. Lipase B from Candida antarctica (CAL-B) was found to
      be the only active biocatalyst, directing the acylation regioselectively towards
      the terminal secondary hydroxyl group of the aglycone side chain. All new
      chromomycin A(3) derivatives showed antitumor activity at the micromolar or lower
      level concentration. Particularly, chromomycin A(3) 4'-vinyladipate showed 3-5
      times higher activity against the four tumor cell lines assayed as compared to
      chromomycin A(3).

PMID- 22647723
TI  - Synthesis and cytotoxicity of 3,4-disubstituted-5-(3,4,5-trimethoxyphenyl)-4H
      1,2,4-triazoles and novel 5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
      derivatives bearing 3,4,5-trimethoxyphenyl moiety.
AB  - A series of 3,4-disubstituted-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazoles and
      some novel 5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles bearing 3,4,5
      trimethoxyphenyl moiety were synthesized and screened for their anticancer
      activity. The preliminary bioassay results indicated that compounds 14 and 16
      showed much stronger cytotoxicity than Doxorubicin against HepG2 cell lines with
      IC(50) values of 0.58 and 3.17 MUM, respectively. Meanwhile compound 16 also
      exhibited a broad spectrum of antitumor activity against MCF-7 and MKN45 with
      IC(50) values of 10.92 and 13.79 MUM, respectively.

PMID- 22647724
TI  - Grandparents' experiences of childhood cancer, part 1: doubled and silenced.
AB  - In this study, the authors examined the experiences of grandparents who have had,
      or have, a grandchild with childhood cancer. Sixteen grandparents were
      interviewed using unstructured interviews, and the data were analyzed according
      to hermeneutic-phenomenological tradition, as guided by the philosophical
      hermeneutics of Hans-Georg Gadamer. Interpretive findings indicate that
      grandparents suffer and worry in many complex ways that include a doubled worry
      for their own children as well as their grandchildren. According to the
      grandparents in this study, this worry was, at times, silenced in efforts to
      protect the parents of the grandchild from the burden of concern for the
      grandparent. Other interpretations include the nature of having one's universe
      shaken, of having lives put on hold, and a sense of helplessness. The
      grandparents in this study offer advice to other grandparents as well as to the
      health care system regarding what kinds of things might have been more helpful to
      them as one level of the family system, who, like other subsystems of the family,
      are also profoundly affected by the event of childhood cancer.

PMID- 22647725
TI  - Grandparents' experiences of childhood cancer, part 2: the need for support.
AB  - In this study, the authors examined the experiences of grandparents who have had,
      or have, a grandchild with childhood cancer. Sixteen grandparents were
      interviewed using unstructured interviews, and the data were analyzed according
      to a hermeneutic-phenomenological tradition, as guided by the philosophical
      hermeneutics of Hans-Georg Gadamer. In Part 1 of this report, interpretive
      findings around worry, burden, silence, the nature of having one's universe
      shaken, of having lives put on hold, and a sense of helplessness were addressed.
      In Part 2, the authors discuss interpretations related to the notions of support,
      burden, protection, energy, standing by, buffering, financial shouldering, and
      relationship. The study concludes with implications that the grandparents in the
      study bring to pediatric nurses in their practices with families in pediatric
      oncology.

PMID- 22647726
TI  - Palliative care afterhours: a review of a phone support service.
AB  - Families caring for a child with incurable cancer require access to support and
      advice round the clock. In Brisbane, Australia, an after-hours phone service was
      established to support these families. This service is operated by oncology
      clinical nurse consultants (CNCs) experienced in pediatric palliative care. This
      is the first review of 8 years of activity, totaling 106 patients and 1954 calls.
      The majority of calls were between parents and CNCs (51%). Updating of the
      patient's condition (18%) was the primary reason for calls, with support and
      reassurance (16%), and symptom management of pain (10%) being the other frequent
      reasons. The majority of calls occurred over the weekends in the morning, with
      only 11% (n = 209) of calls occurring between 10:00 pm and 7:00 am. Of all the
      calls made, 43% (n = 814) were calls managed by the CNC without requiring further
      intervention. Calls were received from throughout Queensland, indicating the
      value of the service in supporting families throughout the state. The after-hours
      phone service has proven to be a simple, effective, and valuable service, which
      is consistently accessed by families, regardless of distance from the hospital.

PMID- 22647727
TI  - Being an expert nurse in pediatric oncology care: nurses' descriptions in
      narratives.
AB  - Pediatric oncology has become a highly specialized area, and the transition from
      novice nurse to expert can be complicated. The aim of this study was to describe
      the perceptions of nurses in pediatric oncology regarding the role of an expert
      nurse in pediatric oncology. Nurses (n = 66) working in pediatric oncology
      participated by writing their narratives. The data were analyzed by means of
      content analysis, and 3 categories were found: an expert has confidence in his or
      her knowledge, an expert provides high-quality care, and an expert is given
      possibilities for professional growth. It can be concluded that when nurses are
      given possibilities for continuous education and reflection, and have a feeling
      of satisfaction at being able to fulfill a child and his or her family's needs,
      this enhances their possibility to become experts and maintain expert competence.

PMID- 22647728
TI  - Memory disorders in children with central nervous system germ cell tumors.
AB  - Memory disorders in children and adolescents with brain tumors are rare, but
      devastating to social, academic, and vocational development. Many pediatric
      patients with intracranial germ cell tumors (GCTs) complain of memory
      difficulties. This study investigated memory across a series of GCT patients. A
      total of 33 GCT patients were retrospectively examined for diagnosis, imaging
      results, intelligence quotient, treatment variables, evidence of increased
      intracranial pressure at diagnosis, and memory. The incidence of amnesia in GCT
      patients was 55%. Memory disturbance could not be predicted by intelligence
      quotient, treatment, location of lesion, or hydrocephalus at diagnosis. The high
      incidence of memory deficits in GCT patients suggests a risk to memory in
      patients with GCT. Formal memory assessment should be considered in all patients
      with central nervous system GCTs. Specific counseling and planning to assist in
      adjustment and to ensure safety should be considered standard care for those with
      memory deficits. The nurse should be instrumental in facilitating understanding
      of this specific injury in the brain tumor population.

PMID- 22647729
TI  - The family impacts of proton radiation therapy for children with brain tumors.
AB  - Children with brain tumors experience significant alterations to their health and
      well-being due to the tumors themselves and oncologic treatment. Caring for
      children with brain tumors can have significant impacts on families, especially
      during and shortly after treatment. In this study of the impacts on families
      caring for children undergoing proton radiation therapy for brain tumors, the
      authors found that families experienced a broad array of negative impacts.
      Families reported feeling like they were living on a roller coaster, feeling that
      others treated them differently, and having to give up things as a family. In the
      multivariable linear regression model, older age of the child and higher reported
      child health-related quality of life were associated with less family impact. The
      presence of concurrent chemotherapy was associated with increased family impact.
      This is the first study to specifically evaluate the families of children being
      treated with proton radiation therapy. The findings in this study are consistent
      with the findings in other studies of children treated with standard therapy that
      show that families experience a variety of stressors and negative impacts while
      their children are receiving treatment. Health care providers should be aware of
      the potential impacts on families of children with brain tumors and their
      treatment to provide robust services to meet the health, psychological, and
      social needs of such children and their families.

PMID- 22647731
TI  - Immune complex-mediated co-ligation of the BCR with FcgammaRIIB results in
      homeostatic apoptosis of B cells involving Fas signalling that is defective in
      the MRL/Lpr model of systemic lupus erythematosus.
AB  - Negative regulation of B cell activation by cognate immune complexes plays an
      important homeostatic role in suppressing B cell hyperactivity and preventing
      consequent autoimmunity. Immune complexes co-ligate the BCR and FcgammaRIIB
      resulting in both growth arrest and apoptosis. We now show that such apoptotic
      signalling involves induction and activation of p53 and its target genes, the pro
      apoptotic Bcl-2 family members, Bad and Bid, as well as nuclear export of p53.
      Collectively, these events result in destabilisation of the mitochondrial and
      lysosomal compartments with consequent activation and interplay of executioner
      caspases and endosomal-derived proteases. In addition, the upregulation of Fas
      and FasL with consequent activation of caspase 8-dependent death receptor
      signalling is required to facilitate efficient apoptosis of B cells. Consistent
      with this role for Fas death receptor signalling, apoptosis resulting from co
      ligation of the BCR and FcgammaRIIB is defective in B cells from Fas-deficient
      MRL/MpJ-Fas(lpr) mice. As these mice develop spontaneous, immune complex-driven
      lupus-like glomerulonephritis, targeting this FcgammaRIIB-mediated apoptotic
      pathway may therefore have novel therapeutic implications for systemic autoimmune
      disease.

PMID- 22647733
TI  - Selective induction of apoptosis and autophagy through treatment with dandelion
      root extract in human pancreatic cancer cells.
AB  - OBJECTIVES: Pancreatic cancer has a 100% mortality rate; the aim of this study is
      to evaluate the efficacy of dandelion root extract (DRE) in inducing apoptosis
      and autophagy in aggressive and resistant pancreatic cancer cells. METHODS: The
      effect of DRE was evaluated using WST-1 (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H
      5-tetrazolio]-1,3-benzene disulfonate) assay. Apoptotic cell death was confirmed
      by nuclear condensation by Hoechst staining and externalization of
      phosphatidylserine to the outer leaflet of the plasma membrane by Annexin-V
      binding assay. Loss of mitochondrial membrane potential was observed using the JC
      1 (5,5',6, 6'-tetrachloro-1,1',3,3' tetraethylbenzimidazolylcarbocyanine iodide)
      dye. The induction of autophagy was detected using a monodansylcadaverine assay
      and this was confirmed by immunofluorescence for light chain 3-II. RESULTS: BxPC
      3 and PANC-1 pancreatic cells were sensitive to aqueous DRE. This extract induces
      selective apoptosis in a dose- and time-dependent manner. Dandelion root extract
      caused the collapse of the mitochondrial membrane potential, leading to prodeath
      autophagy. Normal human fibroblasts were resistant at similar doses. CONCLUSIONS:
      We demonstrate that DRE has the potential to induce apoptosis and autophagy in
      human pancreatic cancer cells with no significant effect on noncancerous cells.
      This will provide a basis on which further research in cancer treatment through
      DRE can be executed.

PMID- 22647732
TI  - Pathogenesis of NOD diabetes is initiated by reactivity to the insulin B chain 9
      23 epitope and involves functional epitope spreading.
AB  - Type 1 diabetes (T1D) is mediated by destruction of pancreatic beta-cells by CD4
      and CD8 T cells specific for epitopes on numerous diabetogenic autoantigens
      resulting in loss of glucose homeostasis. Employing antigen-specific tolerance
      induced by i.v. administration of syngeneic splenocytes ECDI cross-linked to
      various diabetogenic antigens/epitopes (Ag-SP), we show that epitope spreading
      plays a functional role in the pathogenesis of T1D in NOD mice. Specifically, Ag
      SP coupled with intact insulin, Ins B(9-23) or Ins B(15-23), but not GAD65(509
      528), GAD65(524-543) or IGRP(206-214), protected 4-6 week old NOD mice from the
      eventual development of clinical disease; infiltration of immune cells to the
      pancreatic islets; and blocked the induction of DTH responses in a Treg
      dependent, antigen-specific manner. However, tolerance induction in 19-21 week
      old NOD mice was effectively accomplished only by Ins-SP, suggesting Ins B(9-23)
      is a dominant initiating epitope, but autoimmune responses to insulin epitope(s)
      distinct from Ins B(9-23) emerge during disease progression.

PMID- 22647734
TI  - Structure and function of the pancreas in the polycystic kidney rat.
AB  - OBJECTIVES: Mutation in the Pkhd1 gene that encodes a ciliary protein,
      fibrocystin, causes multiple cysts in the kidneys and liver in the polycystic
      kidney (PCK) rat, a model for human autosomal recessive PCK disease. To clarify
      the role of primary cilia in the pancreatic duct, we examined the structure and
      function of the exocrine pancreas of PCK rats. METHODS: Pancreatic juice and bile
      were collected from anesthetized rats. Pancreatic ductal structure was analyzed
      by microdissection and immunohist0chemistry. RESULTS: Histologically pancreatic
      acini were apparently normal, and no cysts were detected in the pancreas. Larger
      pancreatic ducts were irregularly dilated with enhanced expression of AQP1 in
      epithelial cells. The pancreatic duct of PCK rats exhibited significantly (P <
      0.05) higher distensibility than that of wild-type (WT) rat at a physiological
      luminal pressure (3 cm H2O). Pancreatic fluid secretion stimulated with a
      physiological dose of secretin (0.03 nmol/kg per hour) in PCK rats was
      significantly smaller than that in WT, but the differences were not significant
      at higher doses. The amylase responses to carbamylcholine were not different
      between PCK and WT rats. CONCLUSIONS: These findings suggest that
      fibrocystin/primary cilia-dependent mechanisms may play a role in the regulation
      of pancreatic ductal structure and fluid secretion.

PMID- 22647735
TI  - Increased levels of YKL-40 and interleukin 6 in patients with chronic
      pancreatitis and secondary diabetes.
AB  - OBJECTIVES: Circulating levels of YKL-40 and interleukin 6 (IL-6) are elevated in
      patients with type 2 diabetes. We aimed to evaluate YKL-40 levels in patients
      with chronic pancreatitis (CP) with and without secondary diabetes mellitus (DM)
      to investigate whether elevated plasma YKL-40 could play a primary role in the
      pathogenesis of type 2 diabetes or rather represent a consequence of the diabetic
      state. METHODS: Plasma levels of YKL-40 and IL-6 were measured during an oral
      glucose tolerance test in 8 patients with CP and secondary DM, 8 patients with CP
      and normal glucose tolerance (NGT), and 8 healthy control subjects (CTRLs).
      RESULTS: Plasma YKL-40 and IL-6 were significantly higher in patients with CP and
      secondary DM (YKL-40, mean [95% confidence interval], 113 [60-215 ng/mL]; IL-6,
      4.6 [2.3-9.1 pg/mL]) compared to patients with CP and NGT (YKL-40, 42 [28-63
      ng/mL]; IL-6, 1.4 [0.8-2.4 pg/mL]) and healthy control subjects (YKL-40, 46 [31
      69 ng/mL]; IL-6, 1.4 [0.8-2.4 pg/mL]). CONCLUSIONS: Patients with CP and
      secondary DM have elevated levels of YKL-40 and IL-6 compared to CP patients with
      NGT and healthy subjects, suggesting that YKL-40 is not a primary mediator of DM
      but a consequence of the diabetic state.

PMID- 22647736
TI  - An overview on characterization, utilization and leachate analysis of biomedical
      waste incinerator ash.
AB  - Solid waste management is one of the major global environmental issues, as there
      is continuous increase in industrial globalization and generation of waste. Solid
      wastes encompass the heterogeneous mass of throwaways from the urban community as
      well as the homogeneous accumulations of agricultural, industrial and mineral
      wastes. Biomedical waste pose a significant impact on health and environment. A
      proper waste management system should be required to dispose hazardous biomedical
      waste and incineration should be the best available technology to reduce the
      volume of this hazardous waste. The incineration process destroys pathogens and
      reduces the waste volume and weight but leaves a solid material called biomedical
      waste ash as residue which increases the levels of heavy metals, inorganic salts
      and organic compounds in the environment. Disposal of biomedical waste ash in
      landfill may cause contamination of groundwater as metals are not destroyed
      during incineration. The limited space and the high cost for land disposal led to
      the development of recycling technologies and the reuse of ash in different
      systems. In order to minimize leaching of its hazardous components into the
      environment several studies confirmed the successful utilization of biomedical
      waste ash in agriculture and construction sector. This paper presents the
      overview on the beneficial use of ash in agriculture and construction materials
      and its leachate characteristics. This review also stressed on the need to
      further evaluate the leachate studies of the ashes and slag for their proper
      disposal and utilization.

PMID- 22647737
TI  - Spine and axial skeleton injuries in the National Football League.
AB  - BACKGROUND: The majority of previous literature focusing on spinal injuries in
      American football players is centered around catastrophic injuries; however, this
      may underestimate the true number of these injuries in this athletic cohort.
      PURPOSE: The goals of this study were to (1) report the incidence of spinal and
      axial skeleton injuries, both minor and severe, in the National Football League
      (NFL) over an 11-year period; (2) determine the incidence of spinal injury by
      injury type, anatomic location, player position, mechanism of injury, and type of
      exposure (practice vs game); and (3) determine the average number of practices
      and days missed because of injury for each injury type. STUDY DESIGN: Descriptive
      epidemiological study. METHODS: All documented injuries to the cervical,
      thoracic, and lumbar spine; pelvis; ribs; and spinal cord were retrospectively
      analyzed using the NFL's injury surveillance database over a period of 11 seasons
      from 2000 through 2010. The data were analyzed by the number of injuries per
      athlete-exposure, the anatomic location and type of injury, player position,
      mechanism of injury, and number of days missed per injury. RESULTS: A total of
      2208 injuries occurred to the spine or axial skeleton over an 11-season interval
      in the NFL, with a mean loss of 25.7 days per injury. This represented 7% of the
      total injuries during this time period. Of these 2208 injuries, 987 (44.7%)
      occurred in the cervical spine. Time missed from play was greatest for thoracic
      disc herniations (189 days/injury). Other injuries that had a mean time missed
      greater than 30 days included (in descending order) cervical fracture (120
      days/injury), cervical disc degeneration/herniation (85 days/injury), spinal cord
      injury (77 days/injury), lumbar disc degeneration/herniation (52 days/injury),
      thoracic fracture (34 days/injury), and thoracic nerve injury (30 days/injury).
      Offensive linemen were the most likely to suffer a spinal injury, followed by
      defensive backs, defensive linemen, and linebackers. Blocking and tackling were
      the 2 most frequent injury mechanisms reported. CONCLUSION: Spinal and axial
      skeleton injuries occur frequently in the NFL and can result in significant time
      missed from practices and games. Tackling and blocking result in the greatest
      number of injuries, and players performing these activities are the most likely
      to sustain a spinal injury. The results of this study may be used as an impetus
      to formulate strategies to prevent spinal injuries in American football players.

PMID- 22647738
TI  - Anti-infliximab antibodies in inflammatory bowel disease:  prevalence, infusion
      reactions, immunosuppression and response, a meta-analysis.
AB  - Infliximab is a chimeric monoclonal antibody directed against tumour necrosis
      factor-alpha. When used in inflammatory bowel disease, primary nonresponse is
      found in at least 10% of patients, with secondary loss of response occurring in a
      further 10-15% per year. It has been suggested that this may in part be a result
      of the development of anti-infliximab antibodies (ATIs). The aim of the study was
      to determine in patients receiving infliximab the prevalence of ATIs, the effect
      of immunosuppressants on the prevalence of ATI, the effect of ATIs on the
      prevalence of infusion reactions and the effect of ATIs on the rates of
      remission. MEDLINE and EMBASE databases were searched from 1948 and 1980,
      respectively, to October 2011. Eighteen studies involving 3326 patients were
      included. The prevalence of ATIs was 45.8% when episodic infusions of infliximab
      were given and 12.4% when maintenance infliximab was given. The rates of infusion
      reactions were significantly higher in patients with ATIs (relative risk: 2.07;
      95% confidence interval, 1.61-2.67). Immunosuppressants resulted in a 50%
      reduction in the risk of developing ATIs (P<0.00001). However, the presence or
      absence of ATIs did not affect the rates of clinical remission. The prevalence of
      ATIs depends on the regimen of infliximab administration and the use of
      immunosuppressants. Patients who test positive for ATIs are at an increased risk
      of infusion reactions, but have similar rates of remission compared with patients
      who test negative for ATIs. Further analysis is required to determine whether
      loss of response is dependent on the titre of ATIs.

PMID- 22647739
TI  - Heterogeneity in oesophageal dysfunction among patients with different reflux
      symptoms.
AB  - BACKGROUND AND AIM: Ineffective oesophageal motility (IOM) often occurs in
      patients with gastro-oesophageal reflux disease. We aimed to examine the
      hypothesis of whether the presence of IOM differs between patients with gastro
      oesophageal reflux disease with different symptom profiles. METHODS: Eligible
      patients were subclassified according to their predominant symptom of heartburn
      (HB) or acid regurgitation (AR). All patients underwent combined multichannel
      intraluminal impedance and oesophageal manometry. IOM was further graded
      according to the presence of oesophageal transit abnormalities. RESULTS: Fourteen
      healthy individuals, 16 HB patients and 24 AR patients participated in this
      study. The percentage of swallows with complete bolus transit was lower in AR
      than in HB patients during liquid and viscous swallowing (P<0.05). Abnormal bolus
      transit occurred more frequently in AR patients than in HB patients with liquid
      swallows (P<0.001) and viscous swallows (P<0.05). IOM occurred more frequently in
      AR patients than in HB patients (42.7 vs. 12.5%, P=0.049). In patients with IOM,
      severe functional abnormality was more frequently found in AR patients than in HB
      patients (P<0.05). CONCLUSION: This study suggests a potential link between
      oesophageal body dysfunction and individual reflux symptom. Patients with a
      predominant symptom of AR are characterized by greater IOM and defective bolus
      clearance.

PMID- 22647740
TI  - Influence of biliary anastomosis on recovery from secondary biliary cirrhosis.
AB  - OBJECTIVE: The influence of choledochoduodenostomy and choledochojejunostomy on
      the repair of hepatic lesions secondary to biliary obstruction is not well known.
      The aim of the present study was to compare the effects of choledochoduodenostomy
      and choledochojejunostomy on the recovery of these lesions in rats with biliary
      obstruction. METHODS: Rats subjected to 4 weeks of biliary obstruction underwent
      choledochoduodenostomy (n=10) or choledochojejunostomy (n=10). The following
      variables were measured: total bilirubin, alkaline phosphatase,
      aminotransferases, and albumin. Hepatic mitochondrial energy metabolism was
      evaluated by calculating the respiratory control ratio and the oxidative
      phosphorylation index. Hepatic morphometry was used to estimate the mass of the
      hepatocytes, bile ducts, and fibrosis, as well as the hepatic stellate cell
      count. RESULTS: After choledochoduodenostomy and choledochojejunostomy, there was
      a regression in cholestasis and a reduction in the oxidative phosphorylation
      index. However, the total bilirubin, alkaline phosphatase, albumin, and
      respiratory control ratio values improved only after choledochojejunostomy. The
      mass of the liver, spleen, and fibrosis was reduced after both
      choledochoduodenostomy and choledochojejunostomy, but the number of hepatic
      stellate cells increased. After choledochojejunostomy, the hepatic mass recovered
      completely, and the spleen mass was significantly reduced compared with that
      after choledochoduodenostomy. After both choledochoduodenostomy and
      choledochojejunostomy, enterobiliary reflux, biliary contamination, and an
      exacerbation in hepatic inflammation developed. CONCLUSION: Choledochojejunostomy
      was more effective than choledochoduodenostomy, but both techniques induced
      enterobiliary reflux and biliary contamination, which may explain the maintenance
      of hepatic alterations, especially after choledochoduodenostomy.

PMID- 22647741
TI  - Long-term prognosis of an endoscopically treated rectal neuroendocrine tumor:  10
      year experience in a single institution.
AB  - BACKGROUND AND AIM: The endoscopic techniques for treating a small rectal
      neuroendocrine tumor (NET) are performed in most large centers; however, the
      endoscopic management of this condition is not well established. This study was
      designed to determine the long-term prognosis of endoscopically resected NET.
      METHODS: We prospectively studied patients with endoscopically treated rectal NET
      in Seoul St Mary's hospital, between January 2000 and June 2010. The long-term
      outcomes were analyzed in association with the pathological complete resection
      and resection procedures. RESULTS: Seventy-seven patients (48 men and 29 women;
      mean age, 52.3 years; range, 23-77 years) were included. The average NET size was
      7.0+/-2.8 mm (range, 3-16 mm). There was no procedure-related complication. En
      bloc removal was achieved for all lesions, and the rate of histological complete
      resection was 75.3% (58/77). Histological complete resection rates were 71.4%
      (10/14) by conventional endoscopic mucosal resection (EMR), 74.1% (43/58) by a
      two-channel EMR, and 100.0% (5/5) by endoscopic submucosal dissection (ESD).
      Among six patients with incomplete histological resection, two underwent
      additional EMR, two underwent transanal endoscopic microsurgery, and two
      underwent low anterior section with lymph node dissection. The remaining 13
      patients with 'possible' remnant NET underwent regular endoscopic surveillance
      without additional resection. In the latter group, only one patient had local
      recurrence, detected on regular colonoscopic surveillance, after 56 months and
      was treated with additional EMR. All of the patients are alive and 98.7% (76/77)
      of the patients are free from disease during the follow-up periods. CONCLUSION:
      Endoscopic resection is a safe and effective modality and may potentially be used
      for the treatment of NETs smaller than 15 mm in diameter, those confined to the
      submucosal layer, and those without metastasis. Local treatment was believed to
      be curative in cases with complete histological resection. In addition, this
      treatment may have an excellent prognosis in patients with 'possible' remnant
      NET.

PMID- 22647743
TI  - Measles outbreak associated with an arriving refugee - Los Angeles County,
      California, August-September 2011.
AB  - Measles is a highly communicable, acute viral illness with potential for severe
      complications, including death. Although endemic measles was eliminated in the
      United States in 2000 as a result of widespread vaccination, sporadic measles
      outbreaks still occur, largely associated with international travel from measles
      endemic countries and pockets of unvaccinated persons. On August 26, 2011, the
      Los Angeles County Department of Public Health (LACDPH) was notified of suspected
      measles in a refugee from Burma who had arrived in Los Angeles, California, on
      August 24, after a flight from Kuala Lumpur, Malaysia. Passengers on the flight
      included 31 other refugees who then traveled to seven other states, widening the
      measles investigation and response activities. In California alone, 50 staff
      members from LACDPH and the California Department of Public Health (CDPH)
      interviewed and reinterviewed 298 contacts. Measles was diagnosed in three
      contacts of the index patient (patient A). The three contacts with measles were
      two passengers on the same flight as patient A and a customs worker; no secondary
      cases were identified. Delayed diagnosis of measles in patient A and delayed
      notification of health officials precluded use of measles-mumps-rubella (MMR)
      vaccine as an outbreak intervention. This outbreak emphasizes the importance of
      maintaining a high level of vaccination coverage and continued high vigilance for
      measles in the United States, particularly among incoming international
      travelers; clinicians should immediately isolate persons with suspected measles
      and promptly report them to health authorities.

PMID- 22647744
TI  - CDC Grand Rounds: Newborn screening and improved outcomes.
AB  - Newborn screening is the practice of testing every newborn for certain harmful or
      potentially fatal conditions, such as hearing loss and certain genetic,
      endocrine, and metabolic disorders that typically are not otherwise apparent at
      birth. Newborn screening in the United States began in the 1960s. Universal
      newborn screening has become a well-established, state-based, public health
      system involving education, screening, diagnostic follow-up, treatment and
      management, and system monitoring and evaluation. Each year, >98% of
      approximately 4 million newborns in the United States are screened. Through early
      identification, newborn screening provides an opportunity for treatment and
      significant reductions in morbidity and mortality.

PMID- 22647745
TI  - Licensure of 13-valent pneumococcal conjugate vaccine for adults aged 50 years
      and older.
AB  - In 2010, 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth
      Pharmaceuticals, Inc., a subsidiary of Pfizer, Inc.]) was licensed by the Food
      and Drug Administration (FDA) and recommended by the Advisory Committee on
      Immunization Practices (ACIP) for children aged 6 weeks through 71 months for the
      prevention of invasive pneumococcal disease (IPD) caused by the 13 pneumococcal
      serotypes included in the vaccine. PCV13 currently is recommended as a 4-dose
      series for children starting at age 2 months. On December 30, 2011, FDA approved
      PCV13 for prevention of pneumonia and invasive disease caused by PCV13 serotypes
      among adults aged 50 years and older. This report summarizes data on the
      immunogenicity and safety of PCV13 in adults and outlines key additional evidence
      requested by ACIP to formulate recommendations for its use.

PMID- 22647746
TI  - Notes from the field: false-positive measles test - Maine, February 2012.
AB  - On February 7, 2012, the Maine Center for Disease Control and Prevention was
      notified of suspected measles infection in an unvaccinated woman aged 57 years.
      The patient went to her medical provider on January 30 after 3 days of headache
      and fever and 2 days of papular rash. The rash began on her neck and spread to
      her abdomen, legs, and back. Two days later she developed coryza and cough. The
      rash resolved by February 6. A serum specimen collected on January 31
      demonstrated a high titer of measles immunoglobulin M (IgM) and was positive for
      measles immunoglobulin G (IgG) on testing at a reference laboratory.

PMID- 22647747
TI  - Ten years' minimum follow-up with the ileal continent catheterizable reservoir: a
      test of time.
AB  - OBJECTIVE: To evaluate long-term efficacy of an original technique of
      catheterizable ileal reservoir designed for bladder augmentation and/or
      substitution, precluding the need to use a Yang-Monti channel or appendix.
      MATERIALS AND METHODS: Our series comprised 19 patients, operated in 1998-2000,
      with a mean age of 10.1 years (1.6-30). Two were excluded from analysis because
      lost to follow-up after 1.5 and 7 years of surveillance. The primary disease was
      posterior urethral valves (9), myelomeningocele (4), anorectal malformation (1),
      rhabdomyosarcoma (1), medullary astrocytoma (1) and urethral stricture (1).
      Surgery consisted of creating a continent catheterizable ileum-based reservoir
      from a 35-cm ileum segment. RESULTS: Mean follow-up was 11.2 years (10-12.4). All
      16 patients eligible for final evaluation of the procedure were continent,
      excluding two lost of follow-up and one that underwent undiversion. Complications
      noted were: stomal stenosis (3), leakage associated with false passage (1) and
      false passage (1). One patient underwent a Bricker undiversion procedure, an
      appendicovesicostomy was performed in 2, and 1 patient received a Monti channel
      to replace the outlet conduit. The overall complication rate was 29.4% (5/17).
      CONCLUSION: We have confirmed the long-term efficacy of the technique. The
      results are comparable to other 'gold standard' treatments, with the advantage of
      being simpler, faster and sparing the appendix for other uses (Malone antegrade
      continent enema), as well as precluding the need to create a Monti channel.

PMID- 22647749
TI  - Gynecological pelvic infection: what is the role of imaging?
AB  - The diagnosis of pelvic infection is most often made clinically, based on a
      combination of pelvic pain and fever, and possibly a foul discharge. The patient
      is referred to radiology in two very different circumstances: either in the acute
      phase where the challenge is to differentiate a pelvic infection from
      appendicitis, urinary tract infection, and complications of a hemorrhagic luteal
      cyst; or some time after the infectious episode, which may have gone unnoticed,
      and the patient presents with an undetermined pelvic mass that needs to be
      characterized, where the challenge in that situation is not to confuse it with
      ovarian cancer. The signs and symptoms on the pelvic ultrasound, CT scan, and MRI
      suggest the correct diagnosis.

PMID- 22647750
TI  - Meningococcal disease in the Middle East and North Africa: an important public
      health consideration that requires further attention.
AB  - This paper reviews the epidemiological data describing meningococcal disease in
      the Middle East and North Africa (MENA). While meningococcal disease remains an
      important cause of endemic and epidemic disease in many MENA countries, existing
      published epidemiological data appear limited, fragmented, and collected via
      disparate methodologies. Children aged 5 years and younger are predominantly
      affected, though outbreaks of the disease often affect older age groups. Whilst
      serogroup A remains a main cause of meningococcal disease in the region, cases of
      serogroup B, W-135, and Y have been increasingly reported over the last two
      decades in some countries. The Hajj pilgrimage is a key factor influencing
      outbreaks and transmission, and the use of vaccines has minimized the effects on
      the home countries of the pilgrims and has decreased global dissemination of
      disease. Wider use of available polyvalent meningococcal conjugate vaccines may
      provide broader protection against the range of serogroups causing disease or
      posing a threat in the region. In addition, strengthening regional surveillance
      systems and regularly publishing reports with reliable estimates of disease
      incidence, carriage, disease-related mortality, and sequelae may facilitate the
      development of appropriate interventions and public health strategies regarding
      meningococcal disease within the region.

PMID- 22647752
TI  - The antidepressant agomelatine inhibits stress-mediated changes in amino acid
      efflux in the rat hippocampus and amygdala.
AB  - Agomelatine is a potent melatonergic (MT1 and MT2) receptor agonist and 5HT(2C)
      antagonist that is an effective antidepressant in animal models of depression and
      in patients suffering from depression. Our recent studies revealed that acute
      restraint stress increases extracellular levels of glutamate and GABA and that
      these increases in amino acid efflux are inhibited by some but not all
      antidepressants. In view of the increasing evidence supporting a role of amino
      acids in the pathology of depression, the current study examined whether acute
      stress-mediated changes in glutamate and GABA neurotransmission are modulated by
      agomelatine. In agreement with our previous work, acute stress increases
      extracellular glutamate levels in the basolateral nucleus of the amygdala (BLA).
      Similarly, acute stress increases glutamate efflux in the central nucleus of the
      amygdala (CeA). In the hippocampus, acute stress increases glutamate efflux and
      elicits an oscillatory pattern of GABA efflux. Agomelatine administration
      (40mg/kg ip) prior to acute stress inhibited stress-mediated increases in
      glutamate efflux in the hippocampus, BLA and CeA. These results demonstrate that
      acute agomelatine administration effectively inhibits acute stress-mediated
      changes in extracellular glutamate in the rat hippocampus and amygdala. While
      acute stress did not modulate GABA efflux in these regions, agomelatine treatment
      induced an overall reduction of GABA levels in the hippocampus. These data
      suggest that agomelatine modulates amino acid efflux in limbic structures
      implicated in major depressive disorder.

PMID- 22647751
TI  - Long-term resveratrol consumption protects ovariectomized rats chronically
      treated with D-galactose from developing memory decline without effects on the
      uterus.
AB  - Resveratrol (Res) displays potent anti-oxidant activity and is a selective
      estrogen receptor modulator. The aim of the present study is to investigate
      whether Res consumption protects ovariectomized (OVX) rats chronically treated
      with D-galactose (D-gal) from developing memory decline and whether Res
      administration decreases pathological changes in the endometrium and lumen of the
      uterus compared with estradiol replacement therapy. Rats were divided into 6
      groups: 1) Sham control group; 2) OVX+D-gal 100mg/kg group (OVX+D-gal); 3-5) OVX,
      D-gal and Res 20, 40, 80 mg/kg treated groups; and 6) OVX, D-gal and estradiol
      valerate 0.8 mg/kg treated group (ET). Twelve weeks later, in a Morris water maze
      test, the OVX+D-gal rats exhibited a significant memory impairment compared with
      the Sham control rats, which was accompanied by decreased total superoxide
      dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities and an increased
      thiobarbituric acid reactive substances (TBARS) level in the serum. In addition,
      the TBARS and protein carbonylation levels increased in the hippocampus. The
      beneficial roles of the 40 and 80 mg/kg Res treatments were manifested in the
      prevention of memory decline and markedly decreased oxidant stress indices. The
      disruption of the cristae in the mitochondria and the irregular nuclei and
      condensed chromatin in the pyramidal cells of the hippocampal CA1 region were
      also reduced after Res treatment. Furthermore, edema in the endometrium and
      lymphocyte infiltration was avoided in all three of the Res-treated groups
      compared with the ET group. These results suggest that Res is useful not only in
      protecting OVX+D-gal rats from developing memory decline by increasing the anti
      oxidation but also in avoiding the effects on the uterus.

PMID- 22647754
TI  - Unoccupied electronic structure of TiOCl studied using x-ray absorption near-edge
      spectroscopy.
AB  - We study the unoccupied electronic structure of the spin-1/2 quantum magnet TiOCl
      using x-ray absorption near-edge spectroscopy (XANES) at the Ti L and O K edges.
      We acquire data both in total electron and fluorescence yield modes (TEY and FY,
      respectively). While only the latter allows us to access the unconventional low
      temperature spin-Peierls (SP) phase of TiOCl, the signal is found to suffer from
      significant self-absorption in this case. Nevertheless, we conclude from FY data
      that effects of the SP distortion on the electronic structure are absent in the
      incommensurate intermediate phase within experimental accuracy. The similarity of
      room-temperature FY and TEY data, the latter not being obscured by self
      absorption, allows us to use TEY spectra for comparison with simulations. These
      are performed by means of cluster calculations in D(4h) and D(2h) symmetries
      using two different codes. We extract values of the crystal-field splitting and
      parameterize our results using the commonly seen notation of Slater, Racah and
      Butler. In all cases, good agreement with published values from other studies is
      found.

PMID- 22647753
TI  - A simple clinical model predicted diabetes progression among prediabetic
      individuals.
AB  - We followed 1372 prediabetic individuals aged >= 20 years and documented 278
      incident diabetes cases. Family history of diabetes, blood pressure, waist, high
      density lipoprotein cholesterol, and FPG independently associated with diabetes
      progression among women. Among men, family history of premature CVD, waist, and
      FPG remained independently associated with diabetes progression.

PMID- 22647755
TI  - The BECN1 coiled coil domain: an "imperfect" homodimer interface that facilitates
      ATG14 and UVRAG binding.
AB  - The coiled-coil domain of BECN1 serves as a protein interaction platform to
      recruit two major autophagy regulators ATG14 and UVRAG. Our crystal structure of
      the BECN1 coiled-coil domain reveals a homodimer with an imperfect dimer
      interface. This "imperfect" feature favors the formation of a stable BECN1-ATG14
      or BECN1-UVRAG heterodimer over a metastable BECN1 homodimer to promote autophagy
      and/or endocytic pathways.

PMID- 22647756
TI  - Paediatric asthma hospital utilization varies by demographic factors and area
      socio-economic status.
AB  - OBJECTIVES: Associations of emergency department (ED) visits and hospital
      admissions for asthma in children with demographics and area socio-economic
      status (SES) were examined to evaluate long-term trends and identify vulnerable
      populations. STUDY DESIGN: Retrospective population-based trend and cross
      sectional analyses. METHODS: Asthma hospital admissions (2000-2007) and ED visits
      (2005-2007) for children aged 0-14 years living in Orange County, California were
      linked with zip-code-level SES data (2000 US Census). Annual population estimates
      were obtained to calculate age-specific admissions and ED visit rates. Average
      annual percentage changes (AAPC) were calculated with joinpoint analyses. The
      risks of ED visits and hospital admissions were estimated from SES indicators
      with negative binomial regression. RESULTS: Rates of asthma hospital admissions
      and ED visits were highest among children aged 0-4 years, males and African
      Americans, and lowest among Asian/Pacific Islanders. African Americans and
      Hispanics/Latinos were more likely to be uninsured. Asthma admissions decreased
      significantly for all age groups over the study period. The greatest declines per
      100,000 were among children aged 0-4 years (AAPC: -15.3%, 95% confidence interval
      -17.0% to -13.4%). Rates of hospital admissions and ED visits were significantly
      higher in low-SES groups. Hospital admission rates were 30-60% higher and ED
      visits were 80-90% higher in zip codes in the lowest tertile of median household
      income compared with the highest tertile of median household income. CONCLUSIONS:
      Paediatric asthma hospitalizations and ED visit rates are declining in Orange
      County. However, certain groups are disproportionately affected, including those
      living in areas with low SES. This information will help in targeting
      intervention strategies to children at highest risk for severe asthma episodes.

PMID- 22647757
TI  - Expansion of the donor lung pool: use of lungs from smokers.

PMID- 22647758
TI  - Effect of donor smoking on survival after lung transplantation: a cohort study of
      a prospective registry.
AB  - BACKGROUND: The risk that a positive smoking history in lung donors could
      adversely affect survival of transplant recipients causes concern. Conversely,
      reduction of the donor pool by exclusion of donors with positive smoking
      histories could compromise survival of patients waiting to receive a transplant.
      We examined the consequences of donor smoking on post-transplantation survival,
      and the potential effect of not transplanting lungs from such donors. METHODS: We
      analysed the effect of donor smoking on 3 year survival after first adult lung
      transplantation from brain-dead donors done between July 1, 1999, and Dec 31,
      2010, by Cox regression modelling of data from the UK Transplant Registry. We
      estimated the effect of acceptance of lungs from donors with positive smoking
      histories on survival and compared it with the effect of remaining on the waiting
      list for a potential transplant from a donor with a negative smoking history
      donor, by analysing all waiting-list registrations during the same period with a
      risk-adjusted sequentially stratified Cox regression model. FINDINGS: Of 1295
      lung transplantations, 510 (39%) used lungs from donors with positive smoking
      histories. Recipients of such lungs had worse 3 year survival after
      transplantation than did those who received lungs from donors with negative
      smoking histories (unadjusted hazard ratio [HR] 1.46, 95% CI 1.20-1.78; adjusted
      HR 1.36, 1.11-1.67). Independent factors affecting survival were recipient's age,
      donor-recipient cytomegalovirus matching, donor-recipient height difference,
      donor's sex, and total ischaemic time. Of 2181 patients registered on the waiting
      list, 802 (37%) died or were removed from the list without receiving a
      transplant. Patients receiving lungs from donors with positive smoking histories
      had a lower unadjusted hazard of death after registration than did those who
      remained on the waiting list (0.79, 95% CI 0.70-0.91). Patients with septic or
      fibrotic lung disease registered in 1999-2003 had risk-adjusted hazards of 0.60
      (95% CI 0.42-0.87) and 0.39 (0.28-0.55), respectively. INTERPRETATION: In the UK,
      an organ selection policy that uses lungs from donors with positive smoking
      histories improves overall survival of patients registered for lung
      transplantation, and should be continued. Although lungs from such donors are
      associated with worse outcomes, the individual probability of survival is greater
      if they are accepted than if they are declined and the patient chooses to wait
      for a potential transplant from a donor with a negative smoking history. This
      situation should be fully explained to and discussed with patients who are
      accepted for lung transplantation. FUNDING: National Health Service Blood and
      Transplant.

PMID- 22647759
TI  - Liver fibrosis: a bidirectional model of fibrogenesis and resolution.
AB  - Liver fibrosis is the generic response to chronic injury of varying aetiologies.
      A number of common mechanisms link this response to the pathogenesis of fibrosis
      in other organs. While long thought to be relentlessly progressive, there is now
      excellent evidence in both human liver disease and animal models that hepatic
      fibrosis is potentially reversible. The liver therefore provides an excellent
      bidirectional model for the study of fibrogenesis and fibrosis resolution. In
      this article, we will review the evidence for the reversibility of liver
      fibrosis. We will highlight some of the mechanisms responsible for fibrogenesis
      and fibrosis regression, focussing on the role of hepatic myofibroblast
      activation and apoptosis, the importance of matrix metalloproteinases and their
      tissue inhibitors and the central involvement of hepatic macrophages in
      orchestrating this process. Finally, we will briefly discuss what renders liver
      fibrosis irreversible and how this accumulating knowledge base could lead to
      badly needed anti-fibrotic therapies in the future.

PMID- 22647760
TI  - Clinical trials and tribulations--lessons from pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a dreadful disease that lacks adequate
      therapy. A number of treatment trials have been performed and have utilized a
      variety of primary efficacy endpoints. Endpoints that provide the most useful
      efficacy information are clinical endpoints that are directly related to how a
      patient feels, functions or survives. Unfortunately, there are no properly
      established patient-reported outcome measures or measures of functional status in
      IPF, making survival the most robust primary efficacy endpoint. Clinically
      meaningful events such as hospitalization can also provide important efficacy
      information. The use of non-validated surrogate endpoints as primary outcome
      measures often leads to uncertainty when interpreting trial results.

PMID- 22647761
TI  - Treatments in idiopathic pulmonary fibrosis: time for a more targeted approach?
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive age-related lung disease,
      the cause of which is not been fully understood. IPF is a devastating disease
      with mortality worse than many cancers, and treatment options are limited. IPF is
      thought to occur after recurrent injury to the alveolar epithelium followed by
      abnormal repair characterized by the formation of fibroblast and myofibroblast
      foci and excessive deposition of extracellular matrix. An updated classification
      of the idiopathic interstitial pneumonias has encouraged a large number of
      clinical trials. On the whole, these have disappointed. Improvements in molecular
      techniques have developed our understanding of IPF and with it identified new
      pathways and potential targets for therapeutic intervention. These insights are
      leading to interest in biomarkers of disease progression and prognosis and to
      novel anti-fibrotic agents and a more targeted approach to the treatment of IPF.

PMID- 22647762
TI  - Diagnostics and therapeutic interventions in myocardial interstitial disease, a
      previously neglected pathology.
AB  - The emergence of cardiac fibrosis (the prototypal myocardial interstitial
      disease) as an important adverse predictor of risk in heart disease is not
      surprising given that it is largely responsible for cardiac stiffness, provides a
      substrate for rhythm disturbances and promotes tissue hypoxia and development of
      heart failure. Yet, this diagnosis remains difficult, treatment options remain
      limited and underlying mechanisms remain elusive. More recently, however, many
      notable advances in imaging techniques and biomarker discovery have been made to
      improve our understanding of remodelling changes that occur within the myocardial
      interstitium. Ground-breaking new evidence now suggests that fibrosis within the
      heart may not only be reversible but that it also may be amenable to
      pharmacological intervention. In this review, we discuss these recent advances
      and highlight the pressing urgency to better detect myocardial interstitial
      disease and to understand the underlying molecular biology that may enable
      discovery of more specific anti-remodelling therapies.

PMID- 22647763
TI  - Room temperature sonochemical initiation of thiol-ene reactions.
AB  - Thiol-ene 'click' reactions have been initiated for a range of primary alkenes
      using ultrasound in both toluene and water. The method is particularly effective
      in aqueous solutions in the presence of air.

PMID- 22647764
TI  - Salivary gland adenoid cystic carcinoma with cervical lymph node metastasis: a
      preliminary study of 62 cases.
AB  - Adenoid cystic carcinoma (ACC) is an infrequent malignant neoplasm that
      originates most commonly in the major and minor salivary glands of the head and
      neck region. This study provides new information on head and neck ACC with
      cervical lymph node metastasis. Of 616 patients who underwent primary tumour
      resection from 1995 to 2008 in the authors' hospital, 62 cases with cervical
      lymph node metastasis were analyzed. The general incidence of cervical lymph node
      metastasis in ACC was approximately 10%. The base of tongue, mobile tongue and
      mouth floor were the most frequent sites of lymph nodes metastasis, with
      incidences of 19.2%, 17.6% and 15.3%, respectively. Most cases occurred via a
      classic 'tunnel-style' metastasis and the level Ib and II regions were the most
      frequently involved. Primary site and lymphovascular invasion were significantly
      associated with lymph node metastasis. High patient mortality was significantly
      correlated with lymph node positive cases. The tongue-mouth floor complex has a
      high propensity for cervical lymph node metastasis, which occurs through a
      classic 'tunnel-style' metastasis. Peritumoral lymphovascular invasion could be
      taken as strong predictor for lymph node metastasis, which ultimately leads to
      poor prognosis of ACC patient. Selective neck dissection should be considered in
      such cases.

PMID- 22647765
TI  - Use of platelet-rich plasma in the treatment of bisphosphonate-related
      osteonecrosis of the jaw.
AB  - Platelet-rich plasma is a concentrate of growth factors and osteoconductive
      proteins, which can play a major role in bone biology by accelerating and
      enhancing bone repair and regeneration. This paper describes the results of using
      platelet-rich plasma in the management of bisphosphonate-associated necrosis of
      the jaw. Eight patients with a diagnosis of bisphosphonate-associated necrosis of
      the jaw were surgically treated for debridement and removal of necrotic bone,
      followed by application of autologous platelet concentrate enriched with growth
      factors and primary suture of the wound. Patients underwent periodic clinical and
      radiological follow-up examinations. All patients showed clinical improvement and
      oral lesions resolved 2-4 weeks after treatment. After an average 14-month follow
      up period, patients remained asymptomatic. Although not conclusive, the
      combination of necrotic-bone curettage and platelet-rich-plasma to treat
      refractory osteonecrosis of the jaw yielded promising results.

PMID- 22647766
TI  - Message from the editor.

PMID- 22647767
TI  - Message from the president.

PMID- 22647769
TI  - Muscle diseases in the zebrafish.
AB  - Animal models in biomedical research are important for understanding the
      pathological mechanisms of human diseases at a molecular and cellular level.
      Several aspects of mammalian animals, however, may limit their use in modelling
      neuromuscular disorders. Many attributes of zebrafish (Danio rerio) are
      complementary to mammalian experimental systems, establishing the zebrafish as a
      powerful model organism in disease biology. This review focuses on a number of
      key studies using the zebrafish to model hereditary muscle diseases with
      additional emphasis on recent advances in zebrafish functional genomics and drug
      discovery. Increasing research in zebrafish disease models, combined with
      knowledge from mammalian models, will bring novel insights into the disease
      pathogenesis of neuromuscular disorders, as well as facilitate the development of
      effective therapeutic strategies.

PMID- 22647770
TI  - Cytochrome c oxidase-intermediate fibres: importance in understanding the
      pathogenesis and treatment of mitochondrial myopathy.
AB  - An important diagnostic muscle biopsy finding in patients with mitochondrial DNA
      disease is the presence of respiratory-chain deficient fibres. These fibres are
      detected as cytochrome c oxidase-deficient following a sequential cytochrome c
      oxidase-succinate dehydrogenase reaction, often in a mosaic pattern within a
      population of cytochrome c oxidase-normal fibres. Detailed analysis of muscle
      biopsies from patients with various mitochondrial DNA defects shows that a
      spectrum of deficiency exists, as there are a large number of fibres which do not
      correspond to being either completely cytochrome c oxidase-normal (brown
      staining) or cytochrome c oxidase-deficient (blue staining). We have used a
      combination of histochemical and immunocytochemical techniques to show that a
      population of cytochrome c oxidase-intermediate reacting fibres are a gradation
      between normal and deficient fibres. We show that cytochrome c oxidase
      intermediate fibres also have different genetic characteristics in terms of
      amount of mutated and wild-type mtDNA, and as such, may represent an important
      transition between respiratory normal and deficient fibres. Assessing changes in
      intermediate fibres will be crucial to evaluating the responses to treatment and
      in particular to exercise training regimes in patients with mitochondrial DNA
      disease.

PMID- 22647771
TI  - Clinicians' perspectives on a Web-based system for routine outcome monitoring in
      old-age psychiatry in the Netherlands.
AB  - BACKGROUND: In health care, the use of physical parameters to monitor physical
      disease progress is common. In mental health care, the periodic measurement of a
      client's functioning during treatment, or routine outcome monitoring, has
      recently become important. Online delivery of questionnaires has the potential to
      reduce clinicians' resistance to the implementation of routine outcome
      monitoring. Online delivery enables clinicians to receive results on a
      questionnaire in a graphic directly after data entry. This gives them insight
      into the progress of a client at a single glance. OBJECTIVE: To explore
      clinicians' perspectives on a routine outcome monitoring procedure where
      questionnaires and feedback on scores were delivered online. Questionnaires could
      also be filled out on paper and then entered into the online system by a research
      assistant. METHODS: In 2009 we sent an online survey, consisting of five yes-or
      no questions and six open-ended questions, to all clinicians in the 14 mental
      health care organizations working with the routine outcome monitoring system in
      the Netherlands. Of the 172 clinicians contacted, 80 (47%) opened the link and 70
      of these 80 (88%) clinicians completed the survey. RESULTS: Clinicians seldom
      used the graphical feedback from the Web-based system, which indicates that
      direct feedback on scores did not enhance the implementation of routine outcome
      monitoring. Integration into the electronic patient record and more training on
      interpretation and implementation of feedback in daily practice were seen as the
      primary points for further improvement. It was mainly the availability of a
      research assistant that made the routine outcome monitoring procedure feasible.
      CONCLUSIONS: Without a research assistant and training in the interpretation of
      outcomes, software programs alone cannot ensure effective implementation of
      monitoring activities in everyday practice.

PMID- 22647772
TI  - Travel related illness in short-term volunteers from the UK to developing
      countries.
AB  - People of all ages volunteer in developing countries, but little is known about
      the health risks they face. InterHealth, a travel clinic, provides a health
      screening service for short-term overseas volunteers. A cross-sectional study
      design was used to analyse 413 post-travel health questionnaires completed
      between February and November 2009. The sample consisted of volunteers who worked
      on short-term projects in developing countries for a variety of non-governmental
      organisations. At least one sick day was taken by 137 (33.2%) participants.
      Medical care was accessed by 39 (9.6%) participants, and standby medication was
      used by 87 (21.6%) participants. Diarrhoea, especially amongst those aged under
      20 or who visited Latin America, was the most commonly reported health problem
      (95; 23.9%). Possible exposure to schistosomiasis was reported by 56 (13.8%)
      participants, mostly from East Africa. Upon return, the majority of participants
      (371; 91.2%) reported feeling well. The findings of this study show the
      importance of tailored post-travel health screening for short-term overseas
      volunteers. This study may help to tailor pre-departure travel health
      consultations for this group, particularly around food hygiene, hand washing and
      potential exposure to infection, but further research is needed to assess the
      impact of pre-travel health advice.

PMID- 22647773
TI  - Predictors of objectively measured medication nonadherence in adults with heart
      failure.
AB  - BACKGROUND: Medication nonadherence rates are high. The factors predicting
      nonadherence in heart failure remain unclear. METHODS AND RESULTS: A sample of
      202 adults with heart failure was enrolled from the northeastern United States
      and followed for 6 months. Specific aims were to describe the types of
      objectively measured medication adherence (eg, taking, timing, dosing, drug
      holidays) and to identify contributors to nonadherence 6 months after enrollment.
      Latent growth mixture modeling was used to identify distinct trajectories of
      adherence. Indicators of the 5 World Health Organization dimensions of adherence
      (socioeconomic, condition, therapy, patient, and healthcare system) were tested
      to identify contributors to nonadherence. Two distinct trajectories were
      identified and labeled persistent adherence (77.8%) and steep decline (22.3%).
      Three contributors to the steep decline in adherence were identified.
      Participants with lapses in attention (adjusted OR, 2.65; P=0.023), those with
      excessive daytime sleepiness (OR, 2.51; P=0.037), and those with >=2 medication
      dosings per day (OR, 2.59; P=0.016) were more likely to have a steep decline in
      adherence over time than to have persistent adherence. CONCLUSIONS: Two distinct
      patterns of adherence were identified. Three potentially modifiable contributors
      to nonadherence have been identified.

PMID- 22647775
TI  - Experimental arthritis. Pathogenic role of autotaxin and LPA.

PMID- 22647774
TI  - Osteoarthritis. Bow-legged or knock-kneed, MRI studies probe cartilage damage in
      relation to knee alignment and the risk of OA.

PMID- 22647776
TI  - Rheumatoid arthritis. How bad is obesity for RA?

PMID- 22647777
TI  - Therapy. Shot at sciatica relief misses the mark.

PMID- 22647778
TI  - Therapy: TNF inhibition suppresses angiogenic mechanisms implicated in RA.

PMID- 22647779
TI  - Rheumatoid arthritis. Evidence for a genetic component to disease severity in RA.
AB  - Rheumatoid arthritis (RA) is partly heritable; genetic and serological markers
      are known to confer risk of developing pathology. But given clinical
      heterogeneity in RA, can we predict who will develop severe disease? Substantial
      heritability of erosive progression rates has now been identified, but better
      prognostic biomarkers remain wanting.

PMID- 22647781
TI  - Association of ACE gene insertion/deletion polymorphism with birth weight, blood
      pressure levels, and ACE activity in healthy children.
AB  - BACKGROUND: The human angiotensin-converting enzyme (ACE) gene contains a
      polymorphism consisting of either an insertion (I) or a deletion (D) of a 287 bp
      Alu repetitive sequence in intron 16. The potential role of ACE polymorphism in
      the risk of developing hypertension or other cardiovascular disorders has not
      been determined in relation to birth weight (BW). METHODS: The ACE genotype and
      plasma ACE activity were determined in 167 children. Among these children, 60
      were identified with low BW (LBW), and 107 were of normal BW (NBW). RESULTS: ACE
      activity levels were significantly elevated in LBW children compared with the NBW
      group (P < 0.001). There was a significant association of the ACE activity with
      systolic blood pressure (SBP) levels in our population (P < 0.001). Among the ACE
      genotypes, no significant differences were found with respect to BW (P = 0.136).
      However, our results revealed that LBW children had a higher D allele frequency
      than NBW children (P = 0.036). When analyzed by quartiles of SBP or ACE activity,
      we found a greater frequency of both the LBW children and those carrying the DD
      genotype in the highest quartiles of these parameters, whereas the NBW children
      tended to be in the lowest quartile (P < 0.001). Similar results were observed
      with the heterozygote ID children after categorization by quartiles of both SBP
      (P < 0.001) and ACE activity (P = 0.004). CONCLUSIONS: The ACE I/D polymorphism,
      especially the DD genotype, can be interpreted as a major factor in association
      between LBW and high BP levels.

PMID- 22647780
TI  - New tools for classification and monitoring of autoimmune diseases.
AB  - Rheumatologists see patients with a range of autoimmune diseases. Phenotyping
      these diseases for diagnosis, prognosis and selection of therapies is an ever
      increasing problem. Advances in multiplexed assay technology at the gene,
      protein, and cellular level have enabled the identification of 'actionable
      biomarkers'; that is, biological metrics that can inform clinical practice. Not
      only will such biomarkers yield insight into the development, remission, and
      exacerbation of a disease, they will undoubtedly improve diagnostic sensitivity
      and accuracy of classification, and ultimately guide treatment. This Review
      provides an introduction to these powerful technologies that could promote the
      identification of actionable biomarkers, including mass cytometry, protein
      arrays, and immunoglobulin and T-cell receptor high-throughput sequencing. In our
      opinion, these technologies should become part of routine clinical practice for
      the management of autoimmune diseases. The use of analytical tools to deconvolve
      the data obtained from use of these technologies is also presented here. These
      analyses are revealing a more comprehensive and interconnected view of the immune
      system than ever before and should have an important role in directing future
      treatment approaches for autoimmune diseases.

PMID- 22647782
TI  - Polymorphisms of ACE2 are associated with blood pressure response to cold pressor
      test: the GenSalt study.
AB  - BACKGROUND: Increased blood pressure (BP) reactivity to cold pressor test (CPT)
      is a risk factor for hypertension. Genetic factors may influence the variation of
      BP response to CPT among individuals. We explored the association of genetic
      variants in the apelin system genes (APLN, APLNR and ACE2) and BP response to CPT
      in a Chinese population. METHODS: A total of 1,998 Han Chinese participants from
      the Genetic Epidemiology Network of Salt Sensitivity completed a CPT. The
      percentage changes of BP right after the end of ice-water immersion were used as
      the measurement of BP responses to CPT. Twenty-two single nucleotide
      polymorphisms (SNPs) were selected and genotyped, including both tag and
      potential functional SNPs of the APLN, APLNR, and ACE2 genes. A mixed-effect
      linear model was used to assess the association between SNPs and BP responses to
      CPT. RESULTS: In women, three SNPs (rs1514283, rs4646176, and rs879922) of the
      ACE2 gene were significantly associated with the diastolic BP (DBP) response to
      CPT in the general and recessive genetic models after adjustment for multiple
      testing (all false discovery rate q < 0.05). There were no significant
      associations of polymorphisms in APLN and APLNR genes with BP responses to CPT.
      CONCLUSIONS: Our study identified genetic variants in the ACE2 gene that were
      significantly associated with DBP responses to cold stress in the Chinese female
      population. Future studies are warranted to confirm these findings.

PMID- 22647783
TI  - Association of changes in ambulatory arterial stiffness index and pulse wave
      velocity during antihypertensive treatment: the J-CORE study.
AB  - BACKGROUND: We aimed to investigate the association of the change in the
      ambulatory arterial stiffness index (AASI) with that in carotid-femoral pulse
      wave velocity (cfPWV) during treatment with antihypertensive medication. METHODS:
      We enrolled 207 hypertensive patients treated with olmesartan monotherapy for 12
      weeks. Patients were randomly assigned to treatment with hydrochlorothiazide
      (HCTZ; n = 104) or azelnidipine (n = 103) for 24 weeks. The cfPWV and 24-h
      ambulatory blood pressure monitoring (ABPM) results were assessed at baseline and
      24 weeks later. The AASI was defined as 1 minus the regression slope of diastolic
      blood pressure (DBP) on systolic BP (SBP), and was calculated by standard and
      symmetric regression. RESULTS: The changes in the AASI and symmetrical AASI were
      similar between the two groups, while cfPWV in the azelnidipine group decreased
      more than in the HCTZ group (P < 0.001). The change in AASI was not significantly
      correlated with change in cfPWV (r = 0.08, P = 0.26), whereas the change in
      symmetrical AASI was significantly but weakly correlated with change in cfPWV (r
      = 0.22, P < 0.001). The multivariable linear regression analysis revealed that
      the association of the change in symmetrical AASI with change in cfPWV remained
      significant even after adjustments for covariates derived from ABPM (regression
      coefficient (95% confidence interval): 1.33 (0.35-2.30), P = 0.01). CONCLUSIONS:
      The present study demonstrated that neither AASI nor symmetrical AASI may be an
      unequivocal marker of arterial stiffness during antihypertensive treatment.

PMID- 22647784
TI  - Hemodynamic adaptations in different trimesters among nulliparous and multiparous
      pregnant women; the Generation R study.
AB  - BACKGROUND: It has been suggested that maternal vascular adaptations during
      pregnancy differ between nulliparous and multiparous women. Therefore, we
      examined the associations of parity with blood pressure and hemodynamic placental
      function during pregnancy and risks of gestational hypertensive disorders.
      METHODS: The study was embedded in a population-based prospective cohort study
      among 8,377 pregnant women. Information about parity and gravidity was obtained
      at enrollment. Blood pressure was repeatedly measured in each trimester and mean
      pulsatility and resistance indexes of uterine artery were measured in second and
      third trimesters. Information on gestational hypertension and preeclampsia was
      available from medical records. RESULTS: As compared with nulliparous women,
      multiparous women had a lower systolic and diastolic blood pressure in each
      trimester of pregnancy and a slightly higher second and third trimester uterine
      artery resistance and pulsatility indexes (all P values < 0.05), but a lower risk
      of third trimester uterine artery notching (odds ratio (OR) 0.67 (95% confidence
      interval (CI):0.53, 0.84)). The risks of gestational hypertension and
      preeclampsia were lower among multiparous women as compared with nulliparous
      women (OR 0.32 (95% CI: 0.24, 0.43) and OR 0.24 (95% CI: 0.16, 0.37),
      respectively). Among multiparous women only, we did not observe associations of
      parity with hemodynamic parameters. CONCLUSIONS: Nulliparous pregnant women have
      higher blood pressure levels throughout pregnancy and higher risks of notching
      and gestational hypertensive disorders. The first pregnancy might be a major risk
      factor for maternal hemodynamic maladaptations and vascular complications.
      Further studies are needed to explore the underlying mechanisms and consequences
      for fetal growth and development.

PMID- 22647785
TI  - Activation of heme oxygenase and suppression of cGMP are associated with impaired
      endothelial function in obstructive sleep apnea with hypertension.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent disorder that
      increases the risk of systemic hypertension and cardiovascular diseases. Heme
      oxygenase (HO) has been shown to be upregulated in patients with OSA and its
      overexpression in mice causes hypertension. End products of HO are carbon
      monoxide (CO) and bilirubin. CO exerts a pleiotropic action on vasoregulation.
      Despite high prevalence and incident of hypertension in OSA, its pathophysiology
      is not well-understood, particularly in regard to varying susceptibility of
      patients to hypertension. We investigated the role of HO in endothelial
      dysfunction and hypertension in OSA. METHODS: We determined flow-mediated
      vasodilatation (FMD) as a measure of endothelial-dependent vasodilatory capacity,
      exhaled CO, bilirubin, and guanosine 3',5'-cyclic monophosphate (cGMP) in 63
      subjects with OSA (normotensive 27, hypertensive 36) and in 32 subjects without
      OSA (normotensive 19, hypertensive 13). RESULTS: Hypertensive OSA demonstrated
      marked impairment in FMD (8.0 +/- 0.5% vasodilatation) compared to 10.5 +/- 0.8%
      in hypertensives non-OSA (P < 0.01) and 13.5 +/- 0.5% in normotensive OSA (P <
      0.001) and 16.1 +/- 1.1% in normotensive non-OSA (P < 0.0001). HO was upregulated
      and plasma nitric oxide (NO) was significantly increased in hypertensive OSA
      compared to normotensive OSA and hypertensive non-OSA. Conversely, serum cGMP was
      markedly decreased in hypertensive OSA (12.9 +/- 1.8 pmol/ml vs. 20.6 +/- 3.7 in
      normotensive OSA, P = 0.032). There was an inverse relationship between FMD and
      CO and bilirubin concentrations (r = 0.43, P = 0.0001 and r = 0.28, P = 0.01,
      respectively). CONCLUSIONS: These data show that increased CO in the setting of
      elevated NO concentrations is associated with decreased cGMP, impaired FMD, and
      hypertension in patient with OSA.

PMID- 22647786
TI  - Reverse epidemiology of hypertension-mortality associations in hemodialysis
      patients: a long-term population-based study.
AB  - BACKGROUND: Although hypertension (HTN) is a predictor of mortality, recent data
      have questioned the link between baseline HTN and mortality in incident
      hemodialysis (HD) patients. We used Taiwan's National Health Insurance claim data
      (NHRI-NHIRD-99182) to investigate the association. METHODS: In 1999, this
      longitudinal cohort study enrolled 5752 new HD patients. Follow-up began from the
      initiation of HD until death, the end of HD, or the end of 2008. A Kaplan-Meier
      survival analysis was done. Cox proportional hazard analysis was used to identify
      the risk factors for mortality. RESULTS: The prevalence of baseline HTN was
      75.47%. Patients with HTN had a higher prevalence of diabetic mellitus (DM) and
      cardiovascular diseases. The 1-, 5-, and 9-year cumulative survival rates were
      95.5, 63.7 and 41.8% in patients with HTN, and 95.5, 71.0, and 52.0% in those
      without HTN (log-rank test: P <0.001). Multivariate analysis showed that patients
      with baseline HTN may have a higher survival rate (hazard ratio (HR) 0.901, 95%
      confidence interval (CI): 0.819-0.992). After stratification by age and DM, only
      elderly (>=65) patients without DM had a significantly higher survival rate (HR
      0.769, 95% CI: 0.637-0.927). HTN predicts lower mortality with increasing age in
      patients with congestive heart failure (CHF) or coronary artery disease (CAD).
      CONCLUSIONS: There is a reverse (counterintuitive) association between baseline
      HTN and mortality in elderly HD patients without DM and a clear tendency for a
      reverse association with increasing age in patients with CHF or CAD. Further
      study of the association between HTN and mortality in older HD patients may be
      warranted.

PMID- 22647787
TI  - beta-AR polymorphisms and glycemic and lipid parameters in hypertensive
      individuals receiving carvedilol or metoprolol.
AB  - BACKGROUND: beta-Blocker therapy and beta-adrenergic receptor (beta-AR)
      polymorphisms are associated with increases in glucose and lipid levels. We
      investigated associations of common beta1 and beta2-AR single-nucleotide
      polymorphisms (SNPs) with metabolic and lipid variables, and examined
      interactions with beta-blocker treatment assignment to affect these parameters.
      METHODS: This was a post hoc analysis of a double-blinded clinical trial of
      nondiabetic, hypertensive individuals that were randomized to receive carvedilol
      or metoprolol succinate. Fasting glucose, insulin, and lipid levels were measured
      at baseline, 3 months, and after 6 months. Genotypes for beta1-AR SNPs Ser49Gly &
      Gly389Arg and beta2-AR Arg16Gly & Gln27Glu were determined. Multivariable mixed
      models were used to examine associations between beta-AR polymorphisms, metabolic
      parameters, and SNP interactions with beta-blocker therapy (p(interaction)).
      RESULTS: The 322 subjects were mean (s.d.) 51.5 (11.2) years old. After 6 months,
      insulin levels increased by 35.6% on metoprolol and 9.9% on carvedilol (P =
      0.015). In univariate models, the Gln27Gln genotype had higher overall insulin
      levels with beta-blockade compared to the Glu27Glu genotype (P = 0.006). Both
      Arg16Gly (P = 0.012) and Gln27Glu (P = 0.037) SNPs were associated with higher
      triglycerides levels. An interaction between the Arg16Gly SNP and treatment was
      identified (p(int) = 0.048). CONCLUSIONS: These data suggest that insulin and
      triglycerides may be influenced by beta2-AR polymorphisms in patients taking beta
      blockers.

PMID- 22647788
TI  - Selective purification of recombinant neuroactive peptides using the flagellar
      type III secretion system.
AB  - The structure, assembly, and function of the bacterial flagellum involves about
      60 different proteins, many of which are selectively secreted via a specific type
      III secretion system (T3SS) (J. Frye et al., J. Bacteriol. 188:2233-2243, 2006).
      The T3SS is reported to secrete proteins at rates of up to 10,000 amino acid
      residues per second. In this work, we showed that the flagellar T3SS of
      Salmonella enterica serovar Typhimurium could be manipulated to export
      recombinant nonflagellar proteins through the flagellum and into the surrounding
      medium. We translationally fused various neuroactive peptides and proteins from
      snails, spiders, snakes, sea anemone, and bacteria to the flagellar secretion
      substrate FlgM. We found that all tested peptides of various sizes were secreted
      via the bacterial flagellar T3SS. We subsequently purified the recombinant MU
      conotoxin SIIIA (rSIIIA) from Conus striatus by affinity chromatography and
      confirmed that T3SS-derived rSIIIA inhibited mammalian voltage-gated sodium
      channel Na(V)1.2 comparably to chemically synthesized SIIIA. IMPORTANCE:
      Manipulation of the flagellar secretion system bypasses the problems of inclusion
      body formation and cellular degradation that occur during conventional
      recombinant protein expression. This work serves as a proof of principle for the
      use of engineered bacterial cells for rapid purification of recombinant
      neuroactive peptides and proteins by exploiting secretion via the well
      characterized flagellator type III secretion system.

PMID- 22647789
TI  - Antibody pressure by a human monoclonal antibody targeting the 2009 pandemic H1N1
      virus hemagglutinin drives the emergence of a virus with increased virulence in
      mice.
AB  - In 2009, a novel H1N1 influenza A virus (2009 pH1N1) emerged and caused a
      pandemic. A human monoclonal antibody (hMAb; EM4C04), highly specific for the
      2009 pH1N1 virus hemagglutinin (HA), was isolated from a severely ill 2009 pH1N1
      virus-infected patient. We postulated that under immune pressure with EM4C04, the
      2009 pH1N1 virus would undergo antigenic drift and mutate at sites that would
      identify the antibody binding site. To do so, we infected MDCK cells in the
      presence of EM4C04 and generated 11 escape mutants, displaying 7 distinct amino
      acid substitutions in the HA. Six substitutions greatly reduced MAb binding
      (K123N, D131E, K133T, G134S, K157N, and G158E). Residues 131, 133, and 134 are
      contiguous with residues 157 and 158 in the globular domain structure and
      contribute to a novel pH1N1 antibody epitope. One mutation near the receptor
      binding site, S186P, increased the binding affinity of the HA to the receptor.
      186P and 131E are present in the highly virulent 1918 virus HA and were recently
      identified as virulence determinants in a mouse-passaged pH1N1 virus. We found
      that pH1N1 escape variants expressing these substitutions enhanced replication
      and lethality in mice compared to wild-type 2009 pH1N1 virus. The increased
      virulence of these viruses was associated with an increased affinity for alpha2,3
      sialic acid receptors. Our study demonstrates that antibody pressure by an hMAb
      targeting a novel epitope in the Sa region of 2009 pH1N1 HA is able to
      inadvertently drive the development of a more virulent virus with altered
      receptor binding properties. This broadens our understanding of antigenic drift.
      IMPORTANCE: Influenza viruses accumulate amino acid substitutions to evade the
      antibody response in a process known as antigenic drift, making it necessary to
      vaccinate against influenza annually. Mapping human monoclonal antibody (hMAb)
      epitopes is a necessary step towards understanding antigenic drift in humans. We
      defined the specificity of an hMAb that specifically targeted the 2009 pH1N1
      virus and describe a novel epitope. In addition, we identified a previously
      unappreciated potential for antibody escape to enhance the pathogenicity of a
      virus. The escape mutation that we identified with in vitro immune pressure was
      independently reported by other investigators using in vivo selection in
      nonimmune mice. Although in vitro generation of escape mutants is unlikely to
      recapitulate antigenic drift in its entirety, the data demonstrate that pressure
      by a human monoclonal antibody targeting a novel epitope in the hemagglutinin of
      the 2009 pandemic H1N1 virus can inadvertently drive the development of escape
      mutants, of which a subset have increased virulence and altered receptor binding
      properties.

PMID- 22647790
TI  - Contribution of a single host genetic locus to mouse adenovirus type 1 infection
      and encephalitis.
AB  - Susceptibility to mouse adenovirus type 1 (MAV-1) is mouse strain dependent;
      susceptible mice die from hemorrhagic encephalomyelitis. The MAV-1 susceptibility
      quantitative trait locus Msq1 accounts for ~40% of the phenotypic (brain viral
      load) variance that occurs between resistant BALB/c and susceptible SJL mice
      after MAV-1 infection. Using an interval-specific congenic mouse strain (C.SJL
      Msq1(SJL)), in which the SJL-derived allele Msq1(SJL) is present in a BALB/c
      background, we demonstrate that Msq1(SJL) controls the development of high brain
      viral titers in response to MAV-1 infection, yet does not account for the total
      extent of brain pathology or mortality in SJL mice. C.SJL-Msq1(SJL) mice had
      disruption of the blood-brain barrier and increased brain water content after MAV
      1 infection, but these effects occurred later and were not as severe,
      respectively, as those noted in infected SJL mice. As expected, BALB/c mice
      showed minimal pathology in these assays. Infection of SJL- and C.SJL-Msq1(SJL)
      derived primary mouse brain endothelial cells resulted in loss of barrier
      properties, whereas BALB/c-derived cells retained their barrier properties
      despite being equally capable of supporting MAV-1 infection. Finally, we provide
      evidence that organ pathology and inflammatory cell recruitment to the brain
      following MAV-1 infection were both influenced by Msq1. These results validate
      Msq1 as an important host factor in MAV-1 infection and refine the major role of
      the locus in development of MAV-1 encephalitis. They further suggest that
      additional host factors or gene interactions are involved in the mechanism of
      pathogenesis in MAV-1-infected SJL mice. IMPORTANCE: A successful viral infection
      requires both host and viral factors; identification of host components involved
      in viral replication and pathogenesis is important for development of therapeutic
      interventions. A genetic locus (Msq1) controlling mouse adenovirus type 1 (MAV-1)
      brain infection was previously identified. Genes in Msq1 belong to the same
      family of genes associated with susceptibility to other encephalitic viruses, HIV
      1 and West Nile virus. We constructed an interval-specific congenic mouse strain
      to examine the contribution of Msq1 to MAV-1 susceptibility and brain morbidity.
      We compared infected resistant, susceptible, and congenic mice regarding known
      MAV-1 disease manifestations in the brain (survival, viral loads, blood-brain
      barrier disruption, edema, mouse brain endothelial cell barrier properties,
      pathology, and inflammatory cell recruitment) to determine the extent to which
      Msq1 influences MAV-1 infection outcome. Our results showed that Msq1 is a
      critical host genetic factor that controls many aspects of MAV-1 infection.

PMID- 22647791
TI  - [Treatment of rheumatoid swan neck deformity by tenodesis of proximal
      interphalangeal joint with a half flexor digitorum superficialis tendon. About 23
      fingers at 61 months follow-up].
AB  - OBJECTIVES: Surgical treatment of finger swan neck deformities is versatile. We
      aimed to assess the outcome of PIP tenodesis on unfixed deformities, in patients
      suffering from rheumatoid arthritis. METHODS: Twenty-three PIP tenodeses were
      performed on eight patients, using half of a superficialis flexor digitorum
      tendon sutured to A2 pulley through a volar approach. Postoperative splinting, in
      20 degrees  of PIP flexion, was maintained for 4 weeks. The patients were
      assessed retrospectively, at a mean period of 61 months. RESULTS: The PIP flexion
      gained 26 degrees . On the other hand, a 4 degrees -flexion contraction was
      induced. The mean postoperative flexion reached 65 degrees . The PIP
      hyperextension was corrected by 33 degrees . In one same patient, the correction
      was insufficient for the four fingers. The DIP lack of extension was totally
      corrected in 70% of the cases and partially in 30%. Each patient had functional
      improvement. Nineteen good and excellent, and four fair results were reported. No
      major complication was observed. CONCLUSION: This tenodesis seems to be reliable
      and to give good long-term results. It is our intervention of choice for
      rheumatoid flexible swan-neck deformity.

PMID- 22647792
TI  - [Compartment syndrome of the hand].
AB  - Crush injuries of the hand have a bad prognosis. The development of a compartment
      syndrome in crush injuries is feared but rare, and usually affects the radial
      interosseous muscle compartment due to certain anatomic features. The usual
      clinical presentation is an edematous hand held in a slightly intrinsic position
      with severe pain resistant to level 111 analgesia. Passive extension of the
      digits increases the pain. Diagnosis is confirmed by measuring compartmental
      pressure in all compartments so as not to miss a case. The aim of this work is to
      resolve differences in compartmental pressure measurements that may cause
      misdiagnosis and surgical error. The dermofasciectomy is the only treatment that
      stops muscle ischemia and avoids perpetuation of the viscious circle of
      irreversible damage. Functional prognosis is compromised in compartment syndrome
      and the dermofasciectomy cannot be delayed under any circumstance.

PMID- 22647793
TI  - [Homocysteine, vitamin B-12, folic acid and the cognitive decline in the
      elderly].
AB  - Hyperhomocysteinemia is a risk factor for neurological diseases, but the
      underlying pathophysiology has not been adequately explained. Mild
      hyperhomocysteinemia, which is sometimes associated with a low plasma level of
      vitamin B9, B12 and folic acid, is responsible in the toxicity in neural cell by
      activating NMDA receptor. Indeed, even if vitamin supplementation has clearly
      proven its efficiency on lowering plasma levels of homocysteine, recent studies
      do not show any positive effect of vitamin therapy on cognitive function. The
      hypothesis that this therapy is inefficient has been recently reinforced by two
      randomized trials on the effects of vitamin supplementation. Several hypotheses
      still need to be explored: Mechanisms of homocysteine toxicity and that of total
      uselessness of vitamin supplementation; the possible need to complete the actual
      data with further, more powerful studies in order to prove the role of
      homocysteine in the development of neurodegenerative diseases and a clinical
      effect of vitamin therapy. 

PMID- 22647794
TI  - Predictive value of first fasting plasma glucose compared with admission plasma
      glucose for undiagnosed diabetes in a stable cardiology population.
AB  - OBJECTIVES: The study compared the predictive value of admission plasma glucose
      (APG) and first fasting plasma glucose (FPG) in stratifying patients meriting an
      oral glucose tolerance test (OGTT). DESIGN AND METHODS: Characteristics of APG,
      FPG and OGTT 2-hour glucose as well as other blood measurements, physical
      examinations and medical information were assessed in 994 patients without known
      diabetes. RESULTS: The prevalences of diabetes and impaired glucose tolerance
      were 24.6% and 37.9%, according to an OGTT, respectively. The first FPG
      demonstrated stronger predictive value in diagnosing diabetes than APG did both
      in overall and in patients with less clinical value. Compared to the first FPG,
      APG provided less value to coronary artery disease, hypertension and high
      sensitivity C-reactive protein for diabetes screening. CONCLUSIONS: The first FPG
      exerted more predictive value than APG did and was still a preferable reference
      prior to APG in stratifying patients for undiagnosed diabetes by an OGTT.

PMID- 22647795
TI  - On reimbursement reforms and stockpiling of prescription drugs: the case of
      insulin.
AB  - OBJECTIVES: To show that care should be taken in studies which aim at linking
      prescription drug prices to purchased quantities due to anticipation and
      stockpiling effects. METHODS: Using purchasing records for a 20% random sample of
      the entire Danish population, the effects of increasing co-payments are estimated
      using fixed effects techniques. RESULTS: The results indicate that insulin-takers
      react to announced changes in reimbursement policies by stockpiling on their
      medications. CONCLUSION: Using before-and-after comparisons to identify the price
      responsiveness of prescription drug demand can be very misleading, when changes
      in co-payments are announced.

PMID- 22647796
TI  - Our contributive life.

PMID- 22647798
TI  - A national study comparing the tolerability and effectiveness of colon-cleansing
      preparations.
AB  - The aim of this multisite study (N = 412) was to identify which colon-cleansing
      preparations used before colonoscopy work best with specific patient populations.
      A comparative, descriptive approach was used to (1) describe bowel-cleansing
      preparations being used across the United States, (2) compare their cleansing
      effectiveness and tolerability, and (3) compare their effectiveness in patients
      with various health characteristics. A descriptive demographic data form adapted
      from the Society of Gastroenterology Nurses and Associates Minimum Data Set was
      used to collect baseline information, identify preprocedure instructions, and
      describe compliance with preparations. Subjects completed an 11-item subject
      experience with the bowel-cleansing form before their colonoscopy. A colon
      cleanliness scale was completed during the colonoscopy to evaluate the
      effectiveness of the preparation. The preparations revealed a "good" to
      "excellent" rating and there was no statistical difference in the cleansing
      effectiveness of the preparations. Subjects experienced a variety of discomforts.
      Future studies that involve the pooling of data from multiple sites in different
      geographical areas may provide more precise criteria for the selection of colon
      cleansing preparation for specific patients and increase the cultural diversity
      of the sample.

PMID- 22647799
TI  - Clinical utility of the mood and anxiety symptom questionnaire in a chinese
      sample of patients with pancreatic cancer.
AB  - A review of the literature indicates a higher prevalence of depression and
      anxiety in patients with pancreatic carcinoma compared with nonclinical
      populations. The aims of this study were to evaluate the tripartite model for
      assessing symptoms of depression and anxiety and develop a Chinese version of the
      Mood and Anxiety Symptoms Questionnaire-Short Form (MASQ-SF) in patients with
      pancreatic cancer. The final sample consisted of 1,029 patients with pancreatic
      cancer. In line with our hypothesis, results of confirmatory factor analysis
      suggest that the three factors identified fit the hypothesized tripartite model
      well. The Chinese version of the MASQ-SF also exhibited high internal
      consistency. Reliability of the three scales was excellent with all scores
      greater than .79. Cronbach's alpha for the total MASQ-SF was .88. The 1-month
      test-retest reliability was .80. Correlation coefficients among the three
      subscales ranged from .36 to .75. Thus, the Chinese version of the MASQ-SF
      exhibited high levels of reliability and validity, indicating that the Chinese
      version of the MASQ-SF is appropriate for assessing symptoms of depression and
      anxiety in patients with pancreatic cancer. The use of this instrument may help
      researchers to better measure depression and anxiety in patients with pancreatic
      cancer and consequently develop appropriate prevention and treatment
      interventions.

PMID- 22647800
TI  - Impact of an active patient education program on gastrointestinal symptoms in
      women with celiac disease following a gluten-free diet: a randomized controlled
      trial.
AB  - Despite living with a gluten-free diet, Swedish women with celiac disease report
      a higher rate of gastrointestinal symptoms than women without the disease. This
      study was designed to assess the impact of active patient education on
      gastrointestinal symptoms in women with a gluten-free diet. A total of 106
      Swedish women, aged 20 years or older, with celiac disease on a gluten-free diet
      for a minimum of 5 years took part in a randomized controlled trial. The
      intervention group (n = 54) underwent a 10-session educational program, "Celiac
      School," based on problem-based learning. Controls (n = 52) were sent information
      regarding celiac disease at home. The outcome measure was gastrointestinal
      symptoms at 10 weeks and 6 months after intervention, assessed with the
      Gastrointestinal Symptom Rating Scale. After 10 weeks of "Celiac School," the
      participating women reported significant improvements that remained 6 months
      later (p = .029). The controls did not improve significantly. A comparison of the
      development of scores, from baseline to 10 weeks, could not demonstrate a
      significant difference in the overall index between the 2 groups but showed a
      significant improvement concerning 1 of its components, namely the index
      reflecting Abdominal Pain (p = .007). Intervention methods should be refined to
      reach an even more pronounced effect.

PMID- 22647801
TI  - Colonic mucosal pseudolipomatosis: disinfectant colitis?
AB  - Colonic pseudolipomatosis is rare and its pathogenesis is still unclear. A number
      of mechanisms, including mechanical injury during an endoscopic procedure or
      chemical injury by disinfectant, seem to contribute to its pathogenesis. In our
      endoscopy unit, pseudolipomatosis occurred in an epidemic pattern after changing
      the endoscopic disinfectant from 2% glutaraldehyde to peracetic acid compound to
      decrease the length of endoscope reprocessing time. We assumed that
      pseudolipomatosis could be a type of chemical colitis produced by the residual
      disinfectant solution that remained on the surface or in a channel of the
      endoscope after reprocessing. The aim of this report was to highlight a series of
      12 cases of colonic pseudolipomatosis in order to describe the endoscopic and
      pathological features and discuss the harmful effect of disinfectants as a
      possible cause of pseudolipomatosis. To identify the cause of the lesions, we
      systematically reviewed each patient history and the endoscopic and histological
      features. From March 2004 to February 2005, 1276 colonoscopies were performed and
      12 cases (0.94%) of colonic pseudolipomatosis were diagnosed at the Kangnam
      Sacred Heart Hospital of Hallym University. The pathogenesis of colonic
      pseudolipomatosis is not well-known, but our experience indicates the endoscopic
      disinfectant as the probable cause of pseudolipomatosis rather than either
      mechanical traumatic injury or intraluminal air pressure-related injury.

PMID- 22647802
TI  - Developing an advanced practice nurse-led liver clinic.
AB  - End-stage liver disease (ESLD) is a leading cause of digestive disease deaths in
      the United States and continues to increase exponentially every year. Best
      practice does not currently recognize or utilize a clinic practice model for ESLD
      management. Advanced practice registered nurses (APRNs) can impact ESLD disease
      management by implementing an outpatient clinic care model to focus on treatment
      compliance, patient education, improvement of patient outcomes, and reduction in
      hospital admission rates for ESLD patients. A review of 15 research articles was
      completed to determine the impact APRNs can make on chronic care of ESLD
      patients. Results from the review support APRN analysis, assessment, diagnosis,
      treatment, intervention, and evaluation of ESLD patients. The literature reviewed
      also demonstrates that ESLD patients have improved symptom management when
      maintained in an outpatient setting, allowing for decreased hospital and
      insurance expenditures. Following evaluation of the evidence, it was concluded
      that an APRN-led ESLD clinic merits further study.

PMID- 22647803
TI  - Acute visual field defect in ulcerative colitis:  a case report.
AB  - A cerebrovascular occlusive event is a rare complication of IBD, which usually
      occurs during its acute phase, shortly after diagnosis. This association seems to
      be a complex situation, affected by a combination of factors.

PMID- 22647804
TI  - Visceral fat, body mass index, and diverticulitis.

PMID- 22647805
TI  - Drug shortages are likely to continue.
AB  - Although we all continue to strive to provide the best quality care for patients,
      the added difficulties of drug shortages will undoubtedly cause dilemmas that
      must be addressed. Readers are encouraged to read the transcript of the FDA
      public workshop panel at
      http://www.fda.gov/downloads/Drugs/NewsEvents/UCM275801.pdf and communicate with
      their respective nurse leaders to address these issues. In addition, nurses are
      encouraged to subscribe to the One and Only One campaign
      (http://www.oneandonlycampaign.org/).

PMID- 22647806
TI  - Magnetization processes in nanocrystalline gadolinium.
AB  - The thermal decline in magnetization, M(T), at fixed magnetic field (H) under
      'zero-field-cooled' (ZFC) and 'field-cooled' (FC) conditions, the time evolution
      of ZFC magnetization, M(ZFC)(t), at fixed temperature and field, M(H) hysteresis
      loops/isotherms, and ac susceptibility have been measured on polycrystalline Gd
      samples with average grain sizes of d = 12 and 18 nm. The irreversibility in
      magnetization, M(irr), occurring below a characteristic temperature that reduces
      with increasing H, is completely suppressed above a grain-size-dependent
      threshold field, H*. At low fields (H <= 100 Oe), M(irr)(T), like the coercive
      field, H(c)(T), exhibits a minimum at ~16 K and a broad peak at ~50 K before
      going to zero at T ? T(C) (Curie temperature). At fixed temperature (T < T(C))
      and field (H ? H*), where M(irr) is finite, M(ZFC) has a logarithmic dependence
      on time. The magnetic viscosity (S) at H = 1 Oe and T <= 290 K is independent of
      the measurement time above ~2 ms but for t < 2 ms it is strongly time-dependent.
      S(T) peaks at T ? T(C) for H = 1 Oe. A magnetic field reduces the peak height and
      shifts the peak in S(T) to lower temperatures. All the above observations are put
      on a consistent theoretical footing within the framework of a model in which the
      intra-grain magnetizations overcome the energy barriers (brought about by the
      intra-grain and grain-boundary/interfacial magnetic anisotropies) by the thermal
      activation process. These field- and temperature-dependent energy barriers, that
      separate the high-energy metastable (ZFC) state from the stable minimum-energy
      (FC) state, are independent of time for t ? 2 ms and have a very broad
      distribution. We show that the shape anisotropy plays a decisive role in the
      magnetization reversal process, and that the magnetocrystalline and magnetostatic
      fluctuations, prevalent in the grain-boundary and interfacial regions, govern the
      approach-to-saturation of magnetization in nanocrystalline Gd.

PMID- 22647807
TI  - [Treatment of arterial and venous brain ischemia. Experts' recommendations:
      stroke management in the intensive care unit].
AB  - With thrombolysis, intravenous alteplase (0.9 mg/kg body weight, maximum 90 mg),
      with 10% of the dose given as a bolus followed by a 60-minute infusion, is
      recommended within 4.5 hours of onset of ischemic stroke. When indicated,
      intravenous thrombolysis must be initiated as soon as possible. It is possible to
      use intravenous alteplase in patients with seizures at stroke onset, if the
      neurological deficit is related to acute cerebral ischemia. Intravenous alteplase
      can be discussed for use on a case-by-case basis, according to risk of bleeding,
      in selected patients under 18 years and over 80 years of age, although for the
      current European recommendations this would be an off-label use. In hospitals
      with a stroke unit, intravenous thrombolysis is prescribed by a neurologist
      (current French labelling) or a physician having the French certification for
      neurovascular diseases (outside the current French labelling). The patient must
      be monitored in the stroke unit or in case of multiple organ failure in an
      intensive and critical care unit. In hospitals without a stroke unit,
      thrombolysis must be decided by the neurologist from the corresponding stroke
      unit via telemedicine. It is recommended to perform brain imaging 24 hours after
      thromboysis. Intra-arterial thrombolysis can be contemplated on a case-by-case
      basis after multidisciplinary discussion within a 6-hour time window for patients
      with acute middle cerebral artery or carotid occlusions, and within a larger time
      window for patients with basilar artery occlusion, because of their very poor
      spontaneous prognosis. Mechanical thrombectomy can also be contemplated in the
      same situations. With antiplatelet agents, it is recommended that patients
      receive aspirin (160 mg-325 mg) within 48 hours of ischemic stroke onset. When
      thrombolysis is performed or contemplated, it is recommended to delay the
      initiation of aspirin or other antithrombotic drugs for 24 hours. The use of
      antiplatelet agents that inhibit the glycoprotein IIb/IIIa receptor is not
      recommended. Urgent anticoagulation using heparin, low-molecular-weight heparins
      or danaparoid with the goal to treat ischemic stroke patients is not recommended.
      Secondary prevention by anticoagulation can be used, immediately or within the
      first days, after minor ischemic stroke or TIA in patients with a high risk for
      cardioembolism, if uncontrolled hypertension is absent. In patients with large
      infarcts and a high risk for cardioembolism, the timing for initiating
      anticoagulation must be decided on a case-by-case basis. In patients with
      anticoagulation who had an ischemic stroke, the decision to temporarily stop or
      maintain anticoagulation must be made on a case-by-case basis, depending on
      thromboembolic risk, level of anticoagulation at stroke onset and estimated risk
      of hemorrhagic transformation. It is not recommended to use neuroprotective
      agents in ischemic stroke patients. Patients with cerebral venous thrombosis must
      be treated with therapeutic doses of heparin, even in case of concomitant
      intracranial hemorrhage related to cerebral venous thrombosis. If the patient's
      status worsens despite adequate anticoagulation, thrombolysis may be used in
      selected cases. The optimal administration route (local or intravenous),
      thrombolytic agent (urokinase or alteplase) and dose are unknown. There is
      currently no recommendation with regard to local thrombolytic therapy in patients
      with dural sinus thrombosis. Urgent blood transfusions are recommended to reduce
      hemoglobin S to <30% in patients with sickle cell disease and acute ischemic
      stroke.

PMID- 22647808
TI  - [American Academy of Neurology, New Orleans, 21-28 April 2012].

PMID- 22647809
TI  - Dracunculiasis eradication--finishing the job before surprises arise.
AB  - Dracunculiasis (Guinea worm disease) is a preventable waterborne parasitic
      disease that affects the poorest people living in remote rural areas in sub
      Saharan African countries, who do not have access to safe drinking water. The
      Guinea Worm Eradication Program, a 25-year old campaign to rid the world of
      Guinea Worm disease has now reached its final stage accelerating to zero cases in
      all endemic countries. During the 19th and 20th centuries, dracunculiasis was
      common in much of Southern Asia and the African continent. The overall number of
      cases has been reduced tremendously by >=99%, from the 3.32 million cases
      estimated to have occurred in 1986 in Africa to only 1,797 cases reported in 2010
      reported in only five countries (Sudan, Mali, Ethiopia, Chad and Ghana) and Asia
      free of the disease. This achievement is unique in its kind--the only previously
      eradicated disease is smallpox, a viral infection for which vaccination was
      possible--and it has been achieved through primary community-based prevention and
      health education programs. Most efforts need to be taken in two countries, South
      Sudan (comprising 94% or 1,698 out of 1,797 of the cases reported world-wide in
      2010) and Mali because of frequent movements of nomads in a vast area inside and
      outside Mali's borders. All factors favourable to dracunculiasis eradication are
      available including adequate financial resources, community and political support
      and high levels of advocacy. Thus there is no reason that this disabling
      parasitic disease cannot be eradicated soon before surprises arise such as new
      civil conflicts in currently endemic countries.

PMID- 22647810
TI  - Molecular cloning of virB12 gene of Brucella melitensis 16M strain in pET28a
      vector.
AB  - OBJECTIVE: To clone the virB12 gene in pET28a expression vector for production of
      recombinant protein to be used as antigenic component for future serological test
      development. METHODS: Brucella melitensis (B. melitensis) 16M strain was cultured
      and bacterial DNA was extracted by Bioneer AccuPrep(r) Genomic DNA Extraction
      Kit. Oligonucleotide primer pair was designed based on Brucella virB12 gene
      sequence with BamHI and HindIII restriction site at 5' end of the forward and
      reverse primers, respectively. DNA amplification was performed using PrimSTAR(r)
      HS DNA polymerase and the PCR product was purified by DNA AccuPrep(r)Gel
      Purification Kit. Purified DNA was cloned into pJET1.2 cloning vector. VirB12
      gene fragment was excised from pJET1.2 using BamHI/HindIII and subsequently
      subcloned into pET28a (+). RESULTS: Brucella virB12 gene was successfully cloned
      in pJET1.2 and then in pET28a (+) plasmids. PCR and restriction enzyme digestion
      confirms the procedure. CONCLUSION: We cloned and expressed the Brucella virB12
      gene which could be used as antigenic component for specific serological assay
      development.

PMID- 22647811
TI  - Molecular detection of Leishmania isolated from cutaneous leishmaniasis patients
      in Jask County, Hormozgan Province, Southern Iran, 2008.
AB  - OBJECTIVE: To investigate on patients leishmanial infections in Jask County.
      METHODS: Impression smears were prepared from patients in 2008, all, were chequed
      for leishmanial infection by microscopy and molecular assays. Whole DNA was
      extracted using Proteinase K and Phenol/Chloroform/Isoamyl alcohol method. The
      variable segment on minicircles of kinetoplast DNA was amplified via a Nested-PCR
      technique using species-specific primers (LIN R4-LIN 17 -Lin 19). RESULTS: A
      total of 40 smears were prepared from 20 patients, from which, eight samples
      (40%) were positive for leishman body by microscopic method, while, 18 samples
      (90%) were positive, molecularly. The parasite was identified as Leishmania major
      (L. major). CONCLUSION: Zoonotic or Rural cutaneous leishmaniasis is endemic in
      Jask County whose pathogen is L. major. Molecular assays using specific primers
      are very accurate and more sensitive and specific than microscopy which is time
      consuming and needs master microscopists.

PMID- 22647812
TI  - Antihyperglycemic activity, antihyperlipedemic activity, haematological effects
      and histopathological analysis of Sapindus mukorossi Gaerten fruits in
      streptozotocin induced diabetic rats.
AB  - OBJECTIVE: To investigate the antihyperglycemic and antihyperlipidemic properties
      of hydroalcoholic extract of fruits of Sapindus mukorossi Gaerten and its
      beneficial effect on haematological parameters with histopathological analysis in
      streptozotocin induced diabetic rats. METHODS: Sapindus mukorossi fruits extract
      (250 and 500 mg/kg body weight) and standard drug glybenclamide (0.5 mg/kg body
      weight) were administered to diabetic rats. Effect of extract on hyperglycemia,
      hyperlipidemia and hematological parameters was studied in diabetic rats.
      Histopathological changes in diabetic rat pancreas were also observed after
      extract and glybenclamide treatment. RESULTS: Daily oral administration of
      Sapindus mukorossi fruits extract (250 and 500 mg/kg body weight) and
      glybenclamide for 20 days showed beneficial effects on blood glucose level
      (P<0.01) and lipid level. The extract has a favorable effect on the
      histopathological changes of the pancreas in streptozotocin induced diabetes.
      CONCLUSION: These findings reveal that the hydroalcoholic extract of Sapindus
      mukorossi fruits extract possesses antihyperglycemic and antihyperlipidemic
      properties. In addition, the extract can prevent various complications of
      diabetes and improve some haematological parameters.

PMID- 22647814
TI  - Correlates of resistance to gastrointestinal nematode infection in Nigerian West
      African dwarf sheep.
AB  - OBJECTIVE: To investigate correlates of resistance to GI nematode infection in
      Nigerian West African dwarf (WAD) sheep. METHODS: Thirty three sheep were
      randomly assigned to two groups, A (n=27) which were used for experimental
      infections, and B (n=6) which served as uninfected control. Each infected animal
      received weekly escalating infections with infective larvae (60%Haemonchus
      contortus (H. contortus) and 40%Trichostrongylus colubriformis (T. colubriformis)
      for 4 weeks. The responses of all the infected and control sheep were assessed by
      faecal egg count (FEC), worm burden (Wb), packed cell volume (PCV), body weight
      (Bwt), and body condition score (BCS). On the basis of their individual faecal
      egg output, Lambs in group A with epg <=1,000 on any sampling day were classified
      as low faecal egg count (LFEC) phenotype (n=16), those with epg between 1,000 and
      10,000 as intermediate (n=5) and lambs with epg > 10,000 as high feacal egg count
      (HFEC) phenotype (n=6). RESULTS: The difference between the FEC classes was
      highly significant (P=0.001). The BCS and weight gained at the end of the
      experiment by the control and LFEC sheep was significantly higher (P<=0.05) than
      those of the intermediate and HFEC phenotypes. There was a significant and
      negative correlation between the parasitological measures and the trio of BCS,
      PCV and Bwt of sheep. CONCLUSION: The result of the study indicated that the FEC,
      weight gain, PCV, and BCS are correlates and potential selection criteria of GI
      nematode resistant WAD sheep.

PMID- 22647813
TI  - Gastroprotective effect of Acacia nilotica young seedless pod extract: role of
      polyphenolic constituents.
AB  - OBJECTIVE: To systematically evaluate antiulcer potential of Acacia nilotica in
      different ulcer models in rats. METHODS: Different extracts [ethanolic, 50%
      hydroethanolic (50:50), 70% hydroethanolic (70:30) and aqueous] of young seedless
      pods were examined in pylorus ligation induced gastric ulcers in rats. Various
      parameters like, volume of gastric acid secretion, pH, free acidity, total
      acidity, ulcer index, mucin content and antioxidant studies were determined and
      were compared between extract treated, standard and vehicle control following
      ulcer induction. The most active extract was also evaluated in swimming stress
      induced and NSAID induced gastric ulceration. RESULTS: Among different extracts
      of young seedless pods only hydroethanolic extracts showed significant antiulcer
      activity in pyloric ligation induced ulceration. Even more the 70% hydroethanolic
      extract showed better protection as compared to 50% hydroethanolic extract.
      Further 70 % hydroethanolic extract also showed significant mucoprotection in
      swimming stress induced and nonsteroidal antiinflammatory drugs induced gastric
      ulceration. CONCLUSION: The results of present study concluded that the
      hydroethanolic extract of young seedless pods of Acacia nilotica has antiulcer
      activity in pylorus ligation, swimming stress and NSAID induced rat ulcer models.
      The extract containing more amount of phenolic components show high antiulcer
      activity, indicating the phenolic component of the extract to be responsible for
      the activity of the extracts.

PMID- 22647816
TI  - Modeling seasonal leptospirosis transmission and its association with rainfall
      and temperature in Thailand using time-series and ARIMAX analyses.
AB  - OBJECTIVE: To study the number of leptospirosis cases in relations to the
      seasonal pattern, and its association with climate factors. METHODS: Time series
      analysis was used to study the time variations in the number of leptospirosis
      cases. The Autoregressive Integrated Moving Average (ARIMA) model was used in
      data curve fitting and predicting the next leptospirosis cases. RESULTS: We found
      that the amount of rainfall was correlated to leptospirosis cases in both regions
      of interest, namely the northern and northeastern region of Thailand, while the
      temperature played a role in the northeastern region only. The use of
      multivariate ARIMA (ARIMAX) model showed that factoring in rainfall (with an 8
      months lag) yields the best model for the northern region while the model, which
      factors in rainfall (with a 10 months lag) and temperature (with an 8 months lag)
      was the best for the northeastern region. CONCLUSION: The models are able to show
      the trend in leptospirosis cases and closely fit the recorded data in both
      regions. The models can also be used to predict the next seasonal peak quite
      accurately.

PMID- 22647815
TI  - Whole Leea macrophylla ethanolic extract normalizes kidney deposits and recovers
      renal impairments in an ethylene glycol-induced urolithiasis model of rats.
AB  - OBJECTIVE: To investigate the antilithiatic effect of the whole Leea macrophylla
      (L. macrophylla) Roxb (Leeaceae) ethanol extract in ethylene glycol-induced
      urolithiasis model of rats. METHODS: Forty two seven weeks old male wistar albino
      rats were randomly divided into two major groups namely: preventive (n=18) and
      therapeutic (n=24). Preventive group was further subdivided into 3 groups of 6
      rats namely: preventive control (PC), preventive lithiatic control (PLC) and
      preventive lithiatic L. macrophylla (PLLM). Similarly, therapeutic group was also
      subdivided into 4 groups of 6 rats namely: therapeutic control (TC), therapeutic
      lithiatic control (TLC), therapeutic lithitatic L. macrophylla (TLLM) and
      therapeutic lithiatic cystone (TLCYS). The lithiasis was induced by 0.75% (v/v)
      ethylene glycol in the drinking water of all groups except the PC and TC groups.
      The urinary ionic parameters such as calcium, inorganic phosphate, oxalate,
      magnesium & creatinine and renal morphology were altered by ethylene glycol,
      which were partially recovered by 14 d preventive and almost fully recovered by
      28 d therapeutic intervention trials with L. macrophylla extract (500 mg/kg BW
      daily). RESULTS: Significant difference on recovery was observed between
      preventive and therapeutic interventional trials. Anti-urolithiatic effect of
      cystone was significantly (P<0.001) higher than extracts. L. macrophylla extract
      was found nontoxic in the acute toxicity test. CONCLUSION: The results of this
      study demonstrated very promising anti-urolithiatic effect of L. macrophylla
      extract with preventive and therapeutic treatments in this experimental
      condition.

PMID- 22647817
TI  - Antifertility effect of chronically administered Tabernaemontana divaricata leaf
      extract on male rats.
AB  - OBJECTIVE: To investigate the antifertility effect of chronically administered
      Tabernaemontana divaricata (T. divaricata) leaf extract on male rats. METHODS:
      The effect of 50% ethanol extract of T. divaricata leaves on reproduction was
      studied on male rats. The study was divided into four groups of five animals
      each. The first groups (I) received vehicle alone to serve as control. The
      second, third and fourth groups (II, II and IV) of animals were administered the
      leaf extract daily at 50 mg/kg body weight, p.o.,100 mg/kg body weight, p.o., and
      200 mg/kg body weight, p.o., respectively, for a period of 60 days. RESULTS:
      Significant decreases in the weight of testes, epididymis, seminal vesicle and
      ventral prostate were observed. A dose related reduction in the testicular sperm
      count, epididymal sperm count and motility, number of fertile male, ratio between
      delivered and inseminated females and numbers of pups were observed. The testis
      showed a clear correlation between the dose and severity of lesions of
      seminiferous epithelium. In general, the seminiferous tubules appear reduced in
      size with a frequently filled eosinophilic material. Spermatogenesis arrested at
      the secondary spermatocyte stage. Pachytene spermatocytes were undergoing
      degeneration. Disorganigation and sloughing of immature germ cell were visible.
      Leydinf cells were atrophied. No morphological changes were observed in Sertoli
      cells. Significant reduction in serum concentration of luteinizing hormone and
      testosterone were observed. No distinct change in serum FSH concentration was
      recorded. The final body weights of all groups were elevated markedly. No
      alterations were recorded in any hematologiocal parameters. CONCLUSION: It is
      concluded that the 50% ethanol extract of T. divaricata leaf produced dose
      related effect on male reproduction without altering general body metabolism.

PMID- 22647818
TI  - Preliminary study on the antimicrobial activity of Enicostemma littorale using
      different solvents.
AB  - OBJECTIVE: To study the antimicrobial activity of Enicostemma littorale (E.
      littorale) using different solvents. METHODS: Chloroform, methanol and acetone
      extracts of different parts of E. littorale (leaf, stem and root) were evaluated
      for antimicrobial activity using disc diffusion method against some gram-negative
      species such as Escherichia coli, Klebsiella pnemoniae, Pseudomonas aeruginosa,
      Salmonella typhi and gram-positive species Staphylococcus aureus, Bacillus
      cereus, Bacillus subtilis and two fugal species viz., Aspergillus fumigates and
      Aspergillus flavus. RESULTS: The chloroform extracts showed the highest
      antibacterial activity. Among leaf, stem and root extracts, the stem extracts
      showed maximum antibacterial activity. All of the used extracts had no
      significant antifungal activity against Aspergillus fumigates and Aspergillus
      flavus. The chloroform stem extract showed highest activity (about 20 mm
      inhibition zone) against Bacillus subtilis (at 500 mg/mL) followed by the
      methanolic stem extract which showed highest activity against the same organism.
      The lowest antibacterial activity was observed by the acetone leaf extract (about
      8 mm inhibition zone) against Escherichia coli. CONCLUSION: The findings of the
      study indicate littorale could also be a new source for antibiotics discovery.

PMID- 22647819
TI  - Antimotility effects of extracts and fractions of Eastern Nigeria mistletoe
      (Loranthus micranthus Linn).
AB  - OBJECTIVE: To evaluate the antimotility activity of Eastern Nigerian
      mistletoe[Loranthus micranthus (L. micranthus) Linn] parasitic on six different
      host trees viz. Baphia nitida, Persia americana, Kola accuminata, Irvingia
      gabonensis, Citrus simensis and Pentacletra macrophylla (P. mycrophylla).
      METHODS: The antimotility of the methanol extracts and solvent fractions were
      evaluated in castor oil induced diarrheoa in rats. RESULTS: The methanol extracts
      (200 mg/kg, i.p.) inhibited defeacation significantly (P < 0.05) 4 h after
      administration (75.73% to 93.33%) more than that of atropine sulphate (2 mg/kg,
      i.p.) which inhibited defeacation by 80.0%. The methanol extract (200 mg/kg,
      i.p.) of L. micranthus parasitic on P. mycrophylla exhibited significant (P<0.05)
      inhibition in gastrointestinal transit (67.6%) more than that of atropine
      sulphate (2 mg/kg, i.p.) which inhibited gastrointestinal transit by 26.4%. The
      solvent fractions of L. micranthus parasitic on P. mycrophylla at dose levels of
      150 mg/kg inhibited significantly the gastrointestinal transit of mice. Fraction
      F(5) exhibited inhibitory activity which was comparable to loperamide (73.3%).
      CONCLUSION: The methanol extract of L. micranthus parasitic on P. macrophylla
      exhibits higher antimotility activity that other extracts. The solvent fractions
      could serve as source of novel antimotility agents.

PMID- 22647820
TI  - Enhancing effect of ultrasound-mediated microbubble destruction on gene delivery
      into rat kidney via different administration routes.
AB  - OBJECTIVE: To investigate the efficiency of beta-galactosidase gene transfer into
      rat kidney with ultrasound-mediated microbubble destruction via different
      injection routes. METHODS: A total of 25 Wistar rats were randomly divided into 5
      groups. Four groups received a mixture of optison microbubbles (0.2 mL) and lacz
      plasmids (25 MUg) injection via renal artery, tail vein, anterior tibial muscle
      and renal parenchyma, respectively. The control group received a mixture of PBS
      (xx mL) and lacz plasmids (25 MUg) via renal artery. Three days after the gene
      transfer, ultrasound with fixed frequency and power (1 MHz, xxW) was delivered to
      the kidneys for 3 min. The efficiency of the gene transfer and expression was
      evaluated on the basis of beta-galactosidase expression. The side effects of this
      method were evaluated by immunohistological method. RESULTS: beta-galactosidase
      expression could be observed only in tubules but not in glomeruli and
      interstitial area. The efficiency of renal artery group was higher than that of
      tail vein, anterior tibial muscle and renal parenchyma group (P<0.05).
      Immunohistochemical analysis revealed co-expression of beta-galactosidase with a
      roximal tubule marker, megalin, which suggested that ultrasound enhanced gene
      transfer into the proximal tubular epithelial cells. No beta-galactosidase
      expression was observed in the extrarenal organs. There were no evident
      pathological and biochemical changes after gene transfer. CONCLUSIONS: Ultrasound
      mediated microbubble destruction can transfer gene into kidney via renal artery,
      tail vein, anterior tibial muscle and renal parenchyma. Compared with renal
      artery, administrating microbubbles via tail vein and anterior tibial muscle are
      more convenient and less vulnerarious.

PMID- 22647821
TI  - Predicting a single HIV drug resistance measure from three international
      interpretation gold standards.
AB  - OBJECTIVE: To investigate the possibility of combining the interpretation of
      three gold standard interpretation algorithms using weighted heuristics in order
      to produce a single resistance measure. METHODS: The outputs of HIVdb, Rega, ANRS
      were combined to obtain a single resistance profile using the equally weighted
      voting algorithm, accuracy based weighing voting algorithm and the Bayesian based
      weighted voting algorithm techniques. RESULTS: The Bayesian based voting
      combination increased the accuracy of the resistance profile prediction compared
      to phenotype, from 58% to 69%. The equal weighted voting algorithm and the
      accuracy based algorithm both increased the prediction accuracy to 60%.
      CONCLUSION: From the result obtained it is evident that combining the gold
      standard interpretation algorithms may increase the predictive ability of the
      individual interpretation algorithms.

PMID- 22647822
TI  - Analysis of diferentially expressed protein from primary and recurrent ovarian
      cancer serum.
AB  - OBJECTIVE: To study the value of the differentially expressed proteins from
      primary and recurrent ovarian cancer serum for early diagnosis of primary and
      recurrent ovarian cancer. METHODS: WCX kit (Bruker Daltonics GraBH) and matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) technology were used to detect serum samples from 49 patients with primary
      ovarian cancer and 21 patients with recurrent disease. RESULTS: In the mass range
      (Mr) from 1,000 to 12,000 Da, eight differentially expressed protein peaks were
      screened from primary ovarian cancer serum. Among them, four protein peaks with
      Mr 1,457, 1,857, 2,202, 7,761 were lowly expressed and the others with Mr 2,946,
      5,333, 5,859, 5,901 were highly expressed. Ten diferentially expressed protein
      peaks were screened from recurrent ovarian cancer serum. Among them, 1,944,
      1,980, 2,080, 2,661, 2,993, 4,450, 4,659, 5,359 Da protein expressions were
      increased significantly, and 1897, 7868 Da protein expressions were decreased
      significantly. The pattern of primary ovarian cancer was applied to 8 early-stage
      ovarian cancer serum samples, and 7 serum samples were successfully predicted
      with the accuracy of 87.5%. The pattern of recurrent ovarian cancer was applied
      to 9 without pelvic or abdominal mass recurrent ovarian cancer serum samples, and
      8 serum samples were successfully predicted with the accuracy of 88.9%.
      CONCLUSION: Combination of MALDI-TOF-MS and WCX kit technology can directly
      screen the diferrential expressed protein from primary and recurrent ovarian
      cancer serum. They have clinical significance for enhancement of sensitivity and
      specificity of ovarian cancer diagnosis.

PMID- 22647823
TI  - Application of 3D-computed tomography angiography technology in large meningioma
      resection.
AB  - OBJECTIVE: To discuss the role of 3D-computed tomography angiography (3D-CTA)
      technology in reducing injuries of large meningioma surgery. METHODS: 3D-CTA
      preoperative examinations were done in 473 patients with large meningioma
      (simulated group). The images were analyzed by 3D post-processing workstation. By
      observing the major intracranial blood vessels, venous sinus, and the compression
      and invasion pattern in the nerve region, assessing risk level of the surgery,
      simulating the surgical procedures, the surgical removal plan, surgical routes
      and tumor blood-supplying artery embolisation plan were performed. Two hundred
      and fifty seven large meningioma patients who didn't underwent 3D-CTA
      preoperative examination served as control group. The incidence of postoperative
      complications, intraoperative blood transfusion and the operation time were
      compared between these two groups. RESULTS: Compared with the control group, the
      Simpson's grade I and II resection rate was 80.3% (380/473), similar with that of
      the control (81.3%, 209/257). The incidence of postoperative complications in 3D
      CTA simulated group was 37.0% which was significantly lower than that (48.2%) of
      the control (P<0.01). The intraoperative blood supply for simulated group and the
      control was (523.4+/-208.1) mL and (592.0+/-263.3) mL, respectively, with
      significant difference between two groups (P<0.01). And the operation time
      [(314.8+/-106.3)] min was significantly lower in simulated group than that in the
      control [(358.4+/-147.9) min] (P<0.01). CONCLUSION: Application of 3D-CTA imaging
      technology in risk level assessment before large-scaled meningioma resection
      could assist in the rational planning of tumor resectin, surgical routes, and is
      helpful in reducing injuries and complications and enhancing the prognosis of the
      patients.

PMID- 22647824
TI  - Disseminated cysticercosis incidentally diagnosed in a patient of low backache: a
      case report and concise review of literature.
AB  - Disseminated cysticercosis is an uncommon presentation of a common disease.
      Asymptomatic disseminated cysticercosis is rarely reported in literature. Here,
      we are reporting a case of asymptomatic disseminated cysticercosis incidentally
      diagnosed in a patient of low backache. Magnetic resonance imaging of lumbosacral
      spine and neuroimaging done subsequently during the course of evaluation revealed
      diffuse cysticercosis involving abdominal, paraspinal, pelvic and gluteal muscles
      along with neurocysticercosis. Such a disseminated cysticercosis was diagnosed
      incidentally in this patient of low backache with right sciatica and
      radiculopathy at L5-S1 prolapsed intervertebral disc and was subsequently managed
      by L5-S1 interlaminar fenestration and discectomy.

PMID- 22647825
TI  - Dual infection with hepatitis A and E virus presenting with aseptic meningitis: a
      case report.
AB  - We report the case of a young male who presented with features of aseptic
      meningitis and elevated serum liver enzymes, but no symptoms or signs suggestive
      of an acute hepatitis. Subsequently, he was diagnosed with dual infection with
      hepatitis A and E viruses, and recovered completely with symptomatic therapy.
      Isolated aseptic meningitis, unaccompanied by hepatitic features is an unusual
      presentation of a hepatotrophic viral infection, and is yet to be reported with
      hepatitis A and E virus co-infection.

PMID- 22647826
TI  - Comparative study of Helicobacter pylori eradication rates with 5-day quadruple
      "concomitant" therapy and 7-day standard triple therapy.
AB  - BACKGROUND: Several studies have shown the superiority of concomitant quadruple
      therapy containing 3 antibiotics over triple therapy for Helicobacter pylori
      infection. The aim of this study was to compare concomitant quadruple therapy
      with standard triple therapy for first-line H. pylori eradication. METHODS: A
      total of 270 patients with proven H. pylori infection were randomly assigned to
      one of 2 regimens: amoxicillin 1000 mg with clarithromycin 500 mg and
      lansoprazole 30 mg twice daily for 7 days (triple therapy) or amoxicillin 1000 mg
      with clarithromycin 500 mg, metronidazole 500 mg, and lansoprazole 30 mg twice
      daily for 5 days (concomitant therapy). The success of eradication was evaluated
      4 to 5 weeks after completion of treatment. RESULTS: Eradication rates were 86.1%
      in the triple therapy and 91.4% in the concomitant therapy (per protocol), but
      the difference was not statistically significant. Mild adverse events were more
      frequently reported in the concomitant-therapy group (35.6%) than in the triple
      therapy group (25.2%) (P=0.09). CONCLUSIONS: Five-day quadruple concomitant
      therapy eradicated H. pylori in over 90% of patients. Accordingly, concomitant
      therapy is thought to be a promising alternative to triple therapy as a first
      line treatment regimen for H. pylori eradication.

PMID- 22647828
TI  - Interobserver variability in esophageal body measurements with high-resolution
      manometry among new physician users.
AB  - GOALS: To evaluate interobserver variability among 4 new physician users on
      measures of esophageal body function. BACKGROUND: Esophageal high-resolution
      manometry allows observation of esophageal motility by pressure topography plots.
      Little is known about the interobserver variability among physicians. STUDY: Two
      resident and 2 fellow level physicians each interpreted 10 liquid swallows of 20
      esophageal high-resolution manometry studies (n = 200 swallows) using the BioVIEW
      Analysis Suite (Sandhill Scientific Inc.). Studies evaluated were from patients
      referred for evaluation of dysphagia but found to have normal esophageal
      manometry and complete liquid bolus transit. Physicians received an orientation
      session and reviewed recent literature. Each physician recorded contractile front
      velocity (CFV) and distal contractile integral (DCI) for each liquid swallow.
      STATISTICS: Interobserver agreements for CFV and DCI were assessed by intraclass
      correlation (ICC) values. Linear correlations between measurements by 2 readers
      were assessed using linear regression modeling techniques. RESULTS: CFV and DCI
      values of up to 200 data points were analyzed. Four reader results for CFV and
      DCI showed strong agreement although stronger for DCI measures (ICC = 0.94;
      range, 0.91 to 0.98) in comparison with CFV (ICC = 0.79; range, 0.52 to 0.82).
      Further correlation was performed with 2 readers; readers 1 and 2 revealed
      excellent correlation for DCI (r = 0.95, P < 0.001) and good correlation for CFV
      (r = 0.61, P < 0.001). CONCLUSIONS: With a thorough orientation session, good to
      excellent agreement for CFV and DCI measurements can be obtained from new
      physician users. CFV measures exhibit greater interobserver variability possibly
      due to the artifact produced by intraesophageal pressurization.

PMID- 22647827
TI  - Second-line therapy with levofloxacin after failure of treatment to eradicate
      helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000
      patients.
AB  - BACKGROUND: Second-line bismuth-containing quadruple therapy is complex and
      frequently induces adverse effects. A triple rescue regimen containing
      levofloxacin is a potential alternative; however, resistance to quinolones is
      rapidly increasing. AIM: To evaluate the efficacy and tolerability of a second
      line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori
      eradication treatment failed and to assess whether the efficacy of the regimen
      decreases with time. METHODS:  DESIGN: Prospective multicenter study. PATIENTS:
      In whom treatment with a regimen comprising a proton-pump inhibitor,
      clarithromycin, and amoxicillin had failed. INTERVENTION: Levofloxacin (500 mg
      bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. OUTCOME:
      Eradication was confirmed using the C-urea breath test 4 to 8 weeks after
      therapy. Compliance/tolerance: Compliance was determined through questioning and
      recovery of empty medication envelopes. Incidence of adverse effects was
      evaluated by means of a questionnaire. RESULTS: The study sample comprised 1000
      consecutive patients (mean age, 49 +/- 15 y, 42% men, 33% peptic ulcer) of whom
      97% took all medications correctly. Per-protocol and intention-to-treat
      eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95%
      confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year
      2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the
      multivariate analysis, none of the studied variables (including diagnosis and
      year of treatment) were associated with success of eradication. Adverse effects
      were reported in 20% of patients, most commonly nausea (7.9%), metallic taste
      (3.9%), myalgia (3.1%), and abdominal pain (2.9%). CONCLUSIONS: Ten-day
      levofloxacin-containing therapy is an encouraging second-line strategy, providing
      a safe and simple alternative to quadruple therapy in patients whose previous
      standard triple therapy has failed. The efficacy of this regimen remains stable
      with time.

PMID- 22647829
TI  - Primary esophageal meningioma: first literature report.
AB  - We have described a primary esophageal meningioma (MG) clinical case diagnosed in
      a 62-year-old woman; also, we review the literature about extracranial MGs. To
      our knowledge, this is the first case report of an extracranial MG occurring
      primarily in the esophagus. These are benign neoplasms reported classically in
      the central nervous system (CNS). The extrancranial MGs have histopathologic and
      inmunohistochemical features identical to those observed in CNS MGs; thus, the
      main diagnostic hurdle is to keep it in the differential for lesions occurring
      outside the CNS.

PMID- 22647830
TI  - The utility of childhood and adolescent obesity assessment in relation to adult
      health.
AB  - BACKGROUND: High childhood obesity prevalence has raised concerns about future
      adult health, generating calls for obesity screening of young children.
      OBJECTIVE: To estimate how well childhood obesity predicts adult obesity and to
      forecast obesity-related health of future US adults. DESIGN: Longitudinal
      statistical analyses; microsimulations combining multiple data sets. DATA
      SOURCES: National Longitudinal Survey of Youth, Population Study of Income
      Dynamics, and National Health and Nutrition Evaluation Surveys. METHODS: The
      authors estimated test characteristics and predictive values of childhood body
      mass index to identify 2-, 5-, 10-, and 15 year-olds who will become obese
      adults. The authors constructed models relating childhood body mass index to
      obesity-related diseases through middle age stratified by sex and race. RESULTS:
      Twelve percent of 18-year-olds were obese. While screening at age 5 would miss
      50% of those who become obese adults, screening at age 15 would miss 9%. The
      predictive value of obesity screening below age 10 was low even when maternal
      obesity was included as a predictor. Obesity at age 5 was a substantially worse
      predictor of health in middle age than was obesity at age 15. For example, the
      relative risk of developing diabetes as adults for obese white male 15-year-olds
      was 4.5 versus otherwise similar nonobese 15-year-olds. For obese 5-year-olds,
      the relative risk was 1.6. LIMITATION: Main results do not include Hispanics due
      to sample size. Past relationships between childhood and adult obesity and health
      may change in the future. CONCLUSION: Early childhood obesity assessment adds
      limited information to later childhood assessment. Targeted later childhood
      approaches or universal strategies to prevent unhealthy weight gain should be
      considered.

PMID- 22647831
TI  - An inquiry about clinicians' view of the distribution of posttest probabilities:
      possible consequences for applying the threshold concept.

PMID- 22647833
TI  - A pixel-based color image segmentation using support vector machine and fuzzy C
      means.
AB  - Image segmentation is an important tool in image processing and can serve as an
      efficient front end to sophisticated algorithms and thereby simplify subsequent
      processing. In this paper, we present a pixel-based color image segmentation
      using Support Vector Machine (SVM) and Fuzzy C-Means (FCM). Firstly, the pixel
      level color feature and texture feature of the image, which is used as input of
      the SVM model (classifier), are extracted via the local spatial similarity
      measure model and Steerable filter. Then, the SVM model (classifier) is trained
      by using FCM with the extracted pixel-level features. Finally, the color image is
      segmented with the trained SVM model (classifier). This image segmentation can
      not only take full advantage of the local information of the color image but also
      the ability of the SVM classifier. Experimental evidence shows that the proposed
      method has a very effective computational behavior and effectiveness, and
      decreases the time and increases the quality of color image segmentation in
      comparison with the state-of-the-art segmentation methods recently proposed in
      the literature.

PMID- 22647832
TI  - Regulation of the renin-angiotensin system (RAS) in BeWo and HTR-8/SVneo
      trophoblast cell lines.
AB  - OBJECTIVES: The renin-angiotensin system (RAS) is implicated in placentation. We
      determined which RAS pathways are present in two trophoblast cell lines (HTR
      8/SVneo and BeWo cells) and the effects of cAMP, which stimulates renal renin.
      STUDY DESIGN: The effect of cAMP on RAS gene expression and on prorenin and
      angiotensin peptides in HTR-8/SVneo and BeWo cells were investigated. RESULTS: In
      HTR-8/SVneo cells, prorenin mRNA (REN) and protein, (pro)renin receptor (ATP6AP2)
      and angiotensin II type 1 receptor (AGTR1) were stimulated by cAMP (P < 0.05, P <
      0.05, P < 0.001 and P < 0.05, respectively). HTR-8/SVneo cells also expressed
      angiotensinogen (AGT) and angiotensin converting enzyme 1 (ACE1), but did not
      express AGTR2 or ACE2 nor the Ang 1-7 receptor (MAS1). BeWo cells did not express
      REN, and REN was not inducible by cAMP, but cAMP increased ACE2 and MAS1 (both P
      < 0.05) and decreased AGT (P < 0.05). BeWo cells expressed AGT, ACE1, ACE2 and
      MAS1 but not ATP6AP2, AGTR1 nor AGTR2. There was net destruction of Ang II in
      media from HTR-8/SVneo and BeWo incubations and net production of Ang 1-7 by BeWo
      and untreated HTR-8/SVneo cells. CONCLUSION: HTR-8/SVneo cells express REN and
      produce prorenin as well as expressing other RAS genes likely to regulate Ang
      II/AT(1)R interactions and respond to cAMP, like renal renin-secreting cells.
      They are more similar to early gestation placentae and are therefore useful for
      studying effects of renin/ACE/Ang II/AT1R on cell function. BeWo cells express
      the ACE2/Ang 1-7/Mas pathway, which is sensitive to cAMP and therefore are useful
      for studying the effects of ACE2/Ang 1-7/Mas on trophoblast function.

PMID- 22647834
TI  - Her2 negative luminal breast carcinoma and Ki-67 evaluation.
AB  - AIM: To determine the degree of inter-observer variability in defining the
      percentage of Ki-67 immunohistochemical expression in breast carcinoma cases and
      to investigate the validity of using the cut-point of 14% for the administration
      of adjuvant treatment in luminal B (Her2 negative) carcinomas. MATERIALS AND
      METHODS: 99 ER, PR positive, Her2 negative breast carcinomas were consecutively
      selected from the Pathology files of "IASO" Women's Hospital. Ki-67
      immunostaining was evaluated by four pathologists from four different
      institutions. RESULTS: Concerning the whole study group, the inter-observer
      agreement was substantial. Subgroup analysis upon the cases were at least one
      observer evaluated Ki-67 as being less than 14% showed that the inter-observer
      agreement was reduced to fair. Further analysis revealed that both below and
      above the clinicopathological limit of 14%, stands a "grey zone" of about +/-7%,
      in which inter-observer agreement is weak. CONCLUSION: The administration of
      cytotoxic therapy in ER, PR positive, Her2 negative breast carcinomas featuring a
      Ki-67 labeling index of around 14, should be considered with caution. Probably
      decision-making should also take under consideration the whole morphological and
      biological profile of each tumor.

PMID- 22647835
TI  - Maternal PCMT1 gene polymorphisms and the risk of neural tube defects in a
      Chinese population of Lvliang high-risk area.
AB  - Protein-L-isoaspartate (D-aspartate) O-methyltransferase 1 (PCMT1) gene encodes
      for the protein repair enzyme L-isoaspartate (D-aspartate) O-methyltransferase
      (PIMT), which is known to protect certain neural cells from Bax-induced
      apoptosis. Previous study has shown that PCMT1 polymorphisms rs4552 and rs4816 of
      infant are associated with spina bifida in the Californian population. The
      association between maternal polymorphism and neural tube defects is still
      uncovered. A case-control study was conducted to investigate a possible
      association between maternal PCMT1 and NTDs in Lvliang high-risk area of Shanxi
      Province in China, using a high-resolution DNA melting analysis genotyping
      method. We found that increased risk for anencephaly in isolated NTDs compared
      with the normal control group was observed for the G (vs. A) allele (p=0.034,
      OR=1.896, 95% CI, 1.04-3.45) and genotypes GG+GA (p=0.025, OR=2.237, 95% CI, 1.09
      4.57). Although the significance was lost after multiple comparison correction,
      the results implied that maternal polymorphisms in PCMT1 might be a potential
      genetic risk factor for isolated anencephaly in this Chinese population.

PMID- 22647836
TI  - Automatic seizure detection in SEEG using high frequency activities in wavelet
      domain.
AB  - Existing automatic detection techniques show high sensitivity and moderate
      specificity, and detect seizures a relatively long time after onset. High
      frequency (80-500 Hz) activity has recently been shown to be prominent in the
      intracranial EEG of epileptic patients but has not been used in seizure
      detection. The purpose of this study is to investigate if these frequencies can
      contribute to seizure detection. The system was designed using 30 h of
      intracranial EEG, including 15 seizures in 15 patients. Wavelet decomposition,
      feature extraction, adaptive thresholding and artifact removal were employed in
      training data. An EMG removal algorithm was developed based on two features: Lack
      of correlation between frequency bands and energy-spread in frequency. Results
      based on the analysis of testing data (36 h of intracranial EEG, including 18
      seizures) show a sensitivity of 72%, a false detection of 0.7/h and a median
      delay of 5.7 s. Missed seizures originated mainly from seizures with subtle or
      absent high frequencies or from EMG removal procedures. False detections were
      mainly due to weak EMG or interictal high frequency activities. The system
      performed sufficiently well to be considered for clinical use, despite the
      exclusive use of frequencies not usually considered in clinical interpretation.
      High frequencies have the potential to contribute significantly to the detection
      of epileptic seizures.

PMID- 22647838
TI  - An extension to the discriminant analysis of near-infrared spectra.
AB  - Partial least squares discriminant analysis (PLS-DA) is widely used in
      multivariate calibration method. Very often, only one single quantitative model
      is constructed to predict the relationship between the response and the
      independent variables. This approach can easily misidentify, under or over
      estimate the important features contained in the independent variables. The
      results obtained by a single prediction model are thus unstable or correlated to
      spurious spectral variance, particularly when the training set for PLS-DA is
      relatively small. A new algorithm developed by applying the Monte Carlo method to
      PLS-DA, namely MC-PLS-DA, is proposed to classify spectral data obtained from
      near-infrared blood glucose measurement. Noise in the data is removed by randomly
      selecting different subsets from the whole training dataset to generate a large
      number of models. The mean sensitivity and specificity of these models are then
      calculated to determine the model with the best classification rate. The results
      show that the MC-PLS-DA method gives more accurate prediction results when
      compared with other classification methods used for classifying near infrared
      spectroscopic data of blood glucose. Also, the stability of the PLS-DA model is
      enhanced.

PMID- 22647837
TI  - Characterization of the protective capacity of flooring systems using force
      deflection profiling.
AB  - 'Safety floors' aim to decrease the risk of fall-related injuries by absorbing
      impact energy during falls. Ironically, excessive floor deflection during walking
      or standing may increase fall risk. In this study we used a materials testing
      system to characterize the ability of a range of floors to absorb energy during
      simulated head and hip impacts while resisting deflection during simulated single
      leg stance. We found that energy absorption for all safety floors (mean (SD)=14.8
      (4.9)J) and bedside mats (25.1 (9.3)J) was 3.2- to 5.4-fold greater than the
      control condition (commercial carpet). While footfall deflections were not
      significantly different between safety floors (1.8 (0.7)mm) and the control
      carpet (3.7 (0.6)mm), they were significantly higher for two bedside mats.
      Finally, all of the safety floors, and two bedside mats, displayed 3-10 times the
      energy-absorption-to-deflection ratios observed for the baseline carpet. Overall,
      these results suggest that the safety floors we tested effectively addressed two
      competing demands required to reduce fall-related injury risk; namely the ability
      to absorb substantial impact energy without increasing footfall deflections. This
      study contributes to the literature suggesting that safety floors are a promising
      intervention for reducing fall-related injury risk in older adults.

PMID- 22647839
TI  - Nonlinear dynamics of heart rate variability in response to orthostatism and
      hemodialysis in chronic renal failure patients: recurrence analysis approach.
AB  - We studied the response of heart rate variability to hemodialysis and
      orthostatism using traditional linear indexes and 9 recurrence quantification
      analysis indexes to reveal changes in the heart rate dynamics. Twenty healthy
      subjects and 19 chronic renal failure patients treated with hemodialysis thrice a
      week were included. Five-minute heart rate variability time series were obtained
      during supine position (clinostatism) and orthostatism from each participant;
      recordings in renal patients were repeated after hemodialysis. Linear indexes
      were consistent with sympathetic predominance in response to orthostatism in the
      control group. Renal patients before hemodialysis showed increased sympathetic
      predominance in clinostatism, with further increase in orthostatism and
      hemodialysis. In response to orthostatism, 4 recurrence indexes changed in the
      control group, while in renal patients any of them changed before hemodialysis
      and 1 changed after hemodialysis. In clinostatism, renal patients (both before
      and after hemodialysis) had higher laminarity, trapping time, and recurrence time
      than the control group. Recurrence indexes showed that the heart rate dynamics in
      renal patients are different from healthy subjects, suggesting loss of access to
      some regulatory conditions. These findings are consistent with reports of
      sympathetic stimulation induced by hemodialysis and active standing.

PMID- 22647840
TI  - Endoscopic biliary stenting for irretrievable common bile duct stones:
      Indications, advantages, disadvantages, and follow-up results.
AB  - BACKGROUND: The advantages of endoscopic retrograde cholangiopancreatography
      (ERCP) over open surgery have made it the predominant method of treating patients
      with choledocholithiasis. After sphincterotomy, however, 10%-15% of common bile
      duct (CBD) stones cannot be removed with a basket or balloon. Methods for
      managing "irretrievable stones" include surgery; mechanical, intraductal shock
      wave, and extracorporeal shock wave lithotripsy; chemical dissolution; and
      biliary stenting. Endoscopic biliary stent insertion, which is frequently used in
      specific situations, has both advantages and disadvantages. To maximize the
      advantages and minimize the complications of biliary endoprosthesis, it is
      important to recognize its proper indications and to apply the technique in
      proper situations. DATA SOURCES: We reviewed all publications cited in Pubmed and
      published through July 2011 on biliary endoprosthesis in patients with
      irretrievable CBD stones. We analyzed the indications, advantages, disadvantages,
      and long-term follow-up results of this technique. RESULTS: Despite the
      occurrence of related complications, such as cholangitis, endoscopic placement of
      an endoprosthesis may reduce stone size, allowing later clearance of
      unextractable stones. Permanent biliary stenting may be a definitive treatment in
      selected elderly patients who are poor candidates for surgery. CONCLUSION:
      Endoscopic biliary stenting remains a simple and safe method for patients with
      stones difficult to manage by conventional endoscopic methods and those patients
      unfit for surgery or at high surgical risks.

PMID- 22647841
TI  - Defective mitophagy in human Niemann-Pick Type C1 neurons is due to abnormal
      autophagy activation.
AB  - Although traditionally regarded as a cellular adaptive process triggered by
      nutrient deprivation, autophagy in neurons appears to provide an important
      neuroprotective mechanism. Neurons in the brain are protected from starvation,
      and neuronal autophagy serves a critical role in the turnover of abnormal
      proteins and damaged organelles. As post-mitotic, highly polarized cells with
      active protein trafficking, neurons rely heavily on an efficient autophagic
      pathway. Using human embryonic stem cell-derived neurons engineered to mimic the
      cholesterol lysosomal storage disease Niemann Pick type C1 (NPC1), we have shown
      that excessive activation and impaired progression of the autophagic pathway
      conspire to cause abnormal mitochondrial clearance. Defective mitophagy is
      exceptionally severe in human NPC1 neurons, as compared with patient fibroblasts,
      and may explain the selective neuronal failure observed in NPC1 and related
      neurodegenerative disorders.

PMID- 22647842
TI  - Altered distribution of inhibitory interneurons in polymicrogyria.
AB  - There is a high incidence of epilepsy in patients with polymicrogyria; however,
      the epileptogenic mechanisms are largely unknown. The density of parvalbumin
      immunoreactive interneurons was evaluated in an experimental model of
      polymicrogyria, in order to assess the potential changes in the development of
      one population of inhibitory interneurons. Newborn hamsters received an
      intracerebral injection of ibotenate, and all injected animals showed abnormal
      cortical layers characterized by one or two microgyrus in the fronto-parietal
      cortex. A quantitative analysis revealed that the ratios of parvalbumin
      immunoreactive neurons in total neurons were significantly reduced in the medial
      paramicrogyral area, and in the medial and central parts of microgyrus in
      comparison to that in the lateral part of microgyrus (P<0.01). The lateral
      paramicrogyral area had the greatest number of parvalbumin-immunoreactive
      neurons, which was increased significantly in comparison to that in the control
      cortex (P<0.01). We suggest that the callosal, thalamic and intracortical
      afferents to the microgyrus and paramicrogyral area may induce a remarkable
      imbalance between the excitatory and inhibitory activities of the cortical
      structures, associated with the epileptogenic mechanism in polymicrogyria.

PMID- 22647843
TI  - Ictal high-frequency oscillations on scalp EEG recordings in symptomatic West
      syndrome.
AB  - OBJECTIVES: High-frequency oscillations (HFOs) on intracranial
      electroencephalography (EEG) recordings have been reported to be useful to
      identify the epileptogenic zone in intractable epilepsy. We investigated whether
      the ictal HFOs on scalp EEG seen during spasms contributed to identification of
      the epileptogenic zone in symptomatic West syndrome (S-WS). METHODS: In S-WS,
      ictal scalp EEGs were recorded during a series of spasms. The HFOs associated
      with spasms were visualized in the temporally expanded EEG traces and subjected
      to time-frequency analysis. The results on the distribution of HFOs were compared
      with that of cortical lesions indicated by neuroimaging. RESULTS: In the 4
      children examined, HFOs at 80-150 Hz preceded the clinical onsets of spasms. The
      maximum augmentation of these HFOs was larger than that of HFOs at 20-70 Hz. The
      regions of the maximum augmentation of HFOs at 80-150 Hz were identical to the
      lesions detected by neuroimaging. Two patients who underwent dissection of the
      area including the area with HFOs resulted in Engel class I. CONCLUSION: Ictal
      HFOs of spasms on scalp EEG showed a strong association with neuroimaging
      abnormalities presumed to be the epileptogenic zone in S-WS. Ictal HFOs can thus
      be a useful marker for exploring lesions for epilepsy surgery.

PMID- 22647844
TI  - Primum non nocere? Does this also apply to mesothelioma?

PMID- 22647845
TI  - Dynamics and correlation length scales of a glass-forming liquid in quiescent and
      sheared conditions.
AB  - We numerically study dynamics and correlation length scales of a colloidal liquid
      in both quiescent and sheared conditions to further understand the origin of slow
      dynamics and dynamic heterogeneity in glass-forming systems. The simulation is
      performed in a weakly frustrated two-dimensional liquid, where locally preferred
      order is allowed to develop with increasing density. The four-point density
      correlations and bond-orientation correlations, which have been frequently used
      to capture dynamic and static length scales xi in a quiescent condition, can be
      readily extended to a system under steady shear in this case. In the absence of
      shear, we confirmed the previous findings that the dynamic slowing down
      accompanies the development of dynamic heterogeneity. The dynamic and static
      length scales increase with alpha-relaxation time tau(alpha) as a power law
      [Formula: see text], with MU > 0. In the presence of shear, both viscosity and
      tau(alpha) have power-law dependences on shear rate in the marked shear-thinning
      regime. However, the dependence of correlation lengths cannot be described by
      power laws in the same regime. Furthermore, the relation [Formula: see text]
      between length scales and dynamics holds for not too strong shear where thermal
      fluctuations and external forces are both important in determining the properties
      of dense liquids. Thus, our results demonstrate a link between slow dynamics and
      structure in glass-forming liquids even under nonequilibrium conditions.

PMID- 22647846
TI  - A dominant role for meiosis-specific 3' RNA processing in controlling expression
      of a fission yeast cyclin gene.
AB  - Meiotic gene regulation provides a rich source of insight into mechanisms of
      temporal control during development. We previously reported that accumulation of
      many meiotic mRNAs in fission yeast is governed by changes in 3' RNA processing
      and elucidated the molecular basis of this regulatory mechanism for an early
      meiotic gene. Here, we report that cleavage/polyadenylation is also the nexus of
      negative control for middle meiotic genes. Parallel profiles of splicing and
      polyadenylation are observed over a meiotic time course for both rem1 and spo4
      but not for a constitutive control gene. Nevertheless, polyadenylation of rem1
      transcripts is restricted to meiosis by a splicing-independent mechanism. Through
      systematic sequence substitutions, we identified a negative control region (NCR)
      located upstream of the rem1 transcription start site and found that it is
      required to block 3' RNA processing in proliferating cells. Ablation of the NCR
      relieves inhibition regardless of whether the intron is present, absent, or
      carries splice site mutations. Consistent with the previous report of a
      polypeptide encoded by the first exon of rem1, we discovered a second 3'
      processing site just downstream from the 5' splice site. Polyadenylation within
      the intron is activated concurrent with the downstream site during meiosis, is
      controlled by the NCR, and is enhanced when splicing is blocked via 5' junction
      or branch point mutations. Taken together, these data suggest a novel regulatory
      mechanism in which a 5' element modulates the dynamic interplay between splicing
      and polyadenylation.

PMID- 22647847
TI  - Artificial mirtron-mediated gene knockdown: functional DMPK silencing in
      mammalian cells.
AB  - Mirtrons are introns that form pre-miRNA hairpins after splicing to produce RNA
      interference (RNAi) effectors distinct from Drosha-dependent intronic miRNAs.
      Here we present a design algorithm for artificial mirtrons and demonstrate, for
      the first time, efficient gene knockdown of myotonic dystrophy protein kinase
      (DMPK) target sequences in Renilla luciferase 3' UTR and subsequently pathogenic
      DMPK mRNA, causative of Type I myotonic dystrophy, using artificial mirtrons
      cloned as eGFP introns. Deep sequencing of artificial mirtrons suggests that
      functional mature transcripts corresponding to the designed sequence were
      produced in high abundance. They were further shown to be splicing-dependent,
      Drosha-independent, and partially dependent on exportin-5, resulting in the
      precise generation of pre-miRNAs. In a murine myoblast line containing a
      pathogenic copy of human DMPK with more than 500 CUG repeats, the DMPK artificial
      mirtron corrected DM1-associated splicing abnormalities of the Serca-1 mRNA,
      demonstrating the therapeutic potential of mirtron-mediated RNAi. Thus, further
      development and exploitation of the unique properties of mirtrons will benefit
      future research and therapeutic RNAi applications as an alternative to
      conventional RNAi strategies.

PMID- 22647848
TI  - Tumor suppressor gene NGX6 induces changes in protein expression profiles in
      colon cancer HT-29 cells.
AB  - Nasopharyngeal carcinoma-associated gene 6 (NGX6; syn. transmembrane protein 8B,
      TMEM8B) is a recently identified tumor suppressor gene. The underlying mechanisms
      by which the gene inhibits tumor development are not completely known. To further
      understand the function of the gene's protein product NGX6, in the present study,
      we employed two-dimensional difference gel electrophoresis to analyze the protein
      expression profiles of colon cancer HT-29 cells stably transfected with the gene
      NGX6. The differentially expressed proteins were selected and identified by
      matrix-assisted laser desorption/ionization coupled with time-of-flight tandem
      mass spectrometry. The results showed that 12 proteins were down-regulated and 4
      were up-regulated in NGX6-transfected HT-29 cells, compared with vector
      transfected HT-29 cells. The MS results were verified by western blot.
      Bioinformatic analysis showed that these proteins are involved in cell
      proliferation, metastasis, apoptosis, cytoskeletal structure, metabolism, and
      signal transduction, suggesting that NGX6 may inhibit colon cancer through the
      regulation of these biological processes.

PMID- 22647849
TI  - Strongyloides stercoralis infection: a health issue regarding indigenous people
      in Taiwan.
AB  - Strongyloidiasis, caused by Strongyloides stercoralis, is endemic in tropical and
      subtropical regions. Whether or not the infection rate is higher among indigenous
      populations in Taiwan remains unclear. The aim of our study was to assess the
      racial demographics, diagnoses and clinical details of strongyloidiasis. A total
      of 41 patients (27 males and 14 females) with strongyloidiasis at a tertiary
      referral centre in eastern Taiwan in a 21-year period were investigated
      retrospectively. The majority (36/41, 88%) of these patients lived in rural
      townships. Common clinical symptoms were anorexia, abdominal pain, nausea,
      vomiting, fever, coughing and diarrhea. The laboratory abnormalities were anemia,
      eosinophilia, and leukocytosis. The average age of the indigenous patients was
      younger than that of the Hans Chinese patients. Alcoholism among the indigenous
      Taiwanese (all males) was significantly more frequent than in the Hans Chinese,
      which might be one of the reasons that the indigenous males had a higher
      infection rate than Hans Chinese males. The group of patients with intestinal
      strongyloidiasis exhibited a significant lower mortality and a higher recovery
      rate than those with hyperinfection syndrome. Leptospirosis should be considered
      as an underlying factor associated with strongyloidiasis, especially in
      indigenous patients. The relationship and mechanism of leptospira-induced
      overwhelming infection including strongyloidiasis remains to be elucidated.

PMID- 22647850
TI  - DFT and TD-DFT study on the electronic structures and phosphorescent properties
      of 6-phenyl-2,2'-bipyridine tridentate iridium(III) complexes and their isomer.
AB  - We report a theoretical study on three tridentate Ir(III) complexes for organic
      light-emitting diode (OLED) applications. The geometries, electronic structures,
      emission properties, and quantum efficiencies of these Ir(III) complexes
      [(C^N^N)Ir((III))(C^N^N)](+) (denoted as 1 hereafter),
      [(C^N^N)Ir((III))(N^C^N)](+) (2), and [(N^C^N)Ir((III))(N^C^N)](+) (3) were
      investigated theoretically, where C^N^N = 6-phenyl-2,2'-bipyridine, N^C^N = 2,6
      pyridyl-benzene. The ground- and excited-state geometries were optimized at the
      PBE0/LanL2DZ;6-31G* and uPBE0/LanL2DZ;6-31G* level of theory, respectively,
      within acetonitrile solvent simulated by PCM. The emission bands and singlet
      triplet transition properties of 1 and 2 are well reproduced with TD
      PBE0//Stuttgart;cc-pVTZ;cc-pVDZ level of theory. The quantum efficiencies of 1
      and 2 that were obtained upon metallic character analysis are comparable with the
      observed efficiencies. The metallic character analysis also revealed that the
      theoretically designed isomer 3 would highly phosphorescent at 510 nm.

PMID- 22647851
TI  - From striving to thriving: systems thinking, strategy, and the performance of
      safety net hospitals.
AB  - BACKGROUND: Safety net hospitals (SNH) have, on average, experienced declining
      financial margins and faced an elevated risk of closure over the past decade.
      Despite these challenges, not all SNHs are weakening and some are prospering.
      These higher-performing SNHs provide substantial care to safety net populations
      and produce sustainable financial returns. PURPOSE: Drawing on the alternative
      structural positioning and resource-based views, we explore strategic management
      as a source of performance differences across SNHs. METHODOLOGY/APPROACH: We
      employ a mixed-method design, blending quantitative and qualitative data and
      analysis. We measure financial performance using hospital operating margin and
      quantitatively evaluate its relationship with a limited set of well-defined
      structural positions. We further evaluate these structures and also explore the
      internal resources of SNHs based on nine in-depth case studies developed from
      site visits and extensive interviews. FINDINGS: Quantitative results suggest that
      structural positions alone are not related to performance. Comparative case
      studies suggest that higher-performing SNH differ in four respects: (1)
      coordinating patient flow across the care continuum, (2) engaging in partnerships
      with other providers, (3) managing scope of services, and (4) investing in human
      capital. On the basis of these findings, we propose a model of strategic action
      related to systems thinking--the ability to see wholes and interrelationships
      rather than individual parts alone. PRACTICE IMPLICATIONS: Our exploratory
      findings suggest the need to move beyond generic strategies alone and acknowledge
      the importance of underlying managerial capabilities. Specifically, our findings
      suggest that effective strategy is a function of both the internal resources
      (e.g., managers' systems-thinking capability) and structural positions (e.g.,
      partnerships) of organizations. From this perspective, framing resources and
      positioning as distinct alternatives misses the nuances of how strategic
      advantage is actually achieved.

PMID- 22647852
TI  - Increased alpha-synuclein phosphorylation and nitration in the aging primate
      substantia nigra.
AB  - Post-translational modifications of alpha-synuclein occur in the brain of
      patients affected by Parkinson's disease and other alpha-synucleinopathies, as
      indicated by the accumulation of Lewy inclusions containing phosphorylated (at
      serine 129) and nitrated alpha-synuclein. Here we found that phospho-Ser 129 and
      nitrated alpha-synuclein are also formed within dopaminergic neurons of the
      monkey substantia nigra as a result of normal aging. Dopaminergic cell bodies
      immunoreactive for phospho-Ser 129 and nitrated alpha-synuclein were rarely seen
      in adult mature animals but became significantly more frequent in the substantia
      nigra of old primates. Dual labeling with antibodies against phospho-Ser 129 and
      nitrated alpha-synuclein revealed only limited colocalization and mostly stained
      distinct sub-populations of dopaminergic neurons. Age-related elevations of
      modified protein paralleled an increase in the number of neurons immunoreactive
      for unmodified alpha-synuclein, supporting a relationship between higher levels
      of normal protein and enhanced phosphorylation/nitration. Other mechanisms were
      also identified that likely contribute to alpha-synuclein modifications. In
      particular, increased expression of Polo-like kinase 2 within neurons of older
      animals could contribute to phospho-Ser 129 alpha-synuclein production. Data also
      indicate that a pro-oxidant environment characterizes older neurons and favors
      alpha-synuclein nitration. Aging is an unequivocal risk factor for human alpha
      synucleinopathies. These findings are consistent with a mechanistic link between
      aging, alpha-synuclein abnormalities and enhanced vulnerability to
      neurodegenerative processes.

PMID- 22647856
TI  - John Hancock's gout.

PMID- 22647855
TI  - Rituximab-responsive nephrotic syndrome due to minimal change disease in systemic
      lupus erythematosus.

PMID- 22647853
TI  - LEDGF gene silencing impairs the tumorigenicity of prostate cancer DU145 cells by
      abating the expression of Hsp27 and activation of the Akt/ERK signaling pathway.
AB  - Lens epithelium-derived growth factor (LEDGF) maintains survival pathways by
      augmenting the transcription of stress-response genes such as small heat-shock
      protein 27. Recently, aberrant expression of LEDGF was found in prostate cancer
      (PC). Herein, we showed that LEDGF overexpression upregulated Hsp27 in PC cells,
      DU145, PC-3 and LNCaP and promoted antiapoptotic pathways in PCs. We found that
      these cells had higher abundance of Hsp27, which was correlated with the levels
      of LEDGF expression. Transactivation assay in DU145 cells revealed that
      transactivation of Hsp27 was related to the magnitude of LEDGF expression.
      Silencing of LEDGF in DU145 cells abrogated Hsp27 expression and inhibited
      stimulated cell proliferation, invasiveness and migration. These cells were
      arrested in S and G2 phase, and failed to accumulate cyclin B1, and showed
      increased apoptosis. Furthermore, LEDGF-depleted DU145 cells displayed elevated
      Bax and cleaved caspase 9 expression and reduced levels of Bcl2, Bcl-(XL). The
      activated survival pathway(s), ERK1/2 and Akt, were selectively decreased in
      these cells, which characteristically have lower tumorigenicity. Conversely, the
      depleted cells, when re-overexpressed with LEDGF or Hsp27, regained tumorigenic
      properties. Collectively, results reveal the involvement of LEDGF-mediated
      elevated expression of Hsp27-dependent survival pathway(s) in PC. Our findings
      suggest new lines of investigation aimed at developing therapies by targeting
      LEDGF or its aberrant expression-associated stimulated antiapoptotic pathway(s).

PMID- 22647857
TI  - A comparison of arthrocentesis teaching tools: cadavers, synthetic joint models,
      and the relative utility of different educational modalities in improving
      trainees' comfort with procedures.
AB  - BACKGROUND: Each year, rheumatology programs across the country teach incoming
      trainees the skill of arthrocentesis, but the relative effectiveness of various
      teaching techniques has not been assessed in a systematic way. OBJECTIVES: We
      compared approaches to teaching arthrocentesis using cadavers versus anatomic
      models. METHODS: In a pilot study, new rheumatology fellows (n = 7) from 2
      academic institutions were surveyed at 3 points during arthrocentesis training:
      (1) before assuming patient care; (2) after lecture with handouts, followed by
      practice either on cadavers (group A) or on synthetic joint models (group B); and
      (3) 6 weeks into fellowship. Fellows rated their comfort levels for
      arthrocentesis of specific joints using 9-point Likert scales. Fellows also
      retrospectively rated the utility of individual teaching modalities in helping
      them to learn. As a follow-up study, internal medicine residents taking part in a
      month-long rheumatology rotation were similarly surveyed on their comfort level
      performing knee and shoulder arthrocentesis before a cadaver teaching laboratory
      and at the end of their month rotation. RESULTS: The initial mean comfort level
      performing arthrocentesis for all fellows was low (2.01). After the cadaver
      teaching session, group A fellows experienced an overall comfort level increase
      of 1.95, with the largest single increase reported for shoulder arthrocentesis
      (3.86). After the anatomic model teaching session, group B fellows reported a
      mean comfort increase of 1.29, with the largest increase reported for knee
      arthrocentesis (3.13). The subsequent study with residents confirmed significant
      increases in comfort after the cadaver laboratory. When surveyed, the learning
      experience fellows considered most effective was the opportunity to perform
      procedures under supervision and guidance, followed by training on cadavers.
      CONCLUSIONS: Although all teaching interventions for trainees learning
      arthrocentesis were helpful for increasing trainee's comfort with arthrocentesis,
      the use of cadavers seemed to be superior to synthetic anatomic models or
      lectures alone. The specific impact of these teaching interventions on actual
      competence, defined as a performance outcome, deserves additional study.

PMID- 22647858
TI  - Bilateral nephrectomy for the treatment of refractory lupus nephritis with
      features overlapping with thrombotic microangiopathy resembling thrombotic
      thrombocytopenia purpura.
AB  - We report a patient with a diagnosis of systemic lupus erythematosus who
      concurrently developed a syndrome of thrombotic microangiopathy that resembled
      thrombotic thrombocytopenic purpura. The patient underwent plasma exchange and
      immunosuppressive therapy for months before clinical improvement was finally
      achieved through bilateral nephrectomy. Ultimately, our patient died of
      disseminated aspergillosis from prolonged immunosuppression. We believe that
      recognition of bilateral nephrectomy as a potential treatment earlier in her
      course would have spared her this unfortunate demise. We hope that this review of
      current literature will help the reader to consider bilateral nephrectomy in
      patients with refractory systemic lupus erythematosus with clinical overlap of
      thrombotic microangiopathy resembling thrombotic thrombocytopenic purpura.

PMID- 22647859
TI  - Basic science for the clinician 56: inducible T-cell costimulator--the world of
      costimulation gets more complicated...and interesting.
AB  - They say that nothing is assured in this world but change. And this applies in a
      cynical way to immunology: nothing is assured--we can never rest with an
      assumption that we know it all because there are always more apparent
      complications when analyzing immune mechanisms (someday, perhaps we will arrive
      on a "grand scheme" that elegantly explains it all, just as our brethren in
      particle physics seek the Higgs boson and the completion of a better model--I am
      not holding my breath awaiting completion of our task!). In a recent article in
      this series, we explored CTLA4 as a counterregulator of the CD28-CD80/86
      costimulatory pathway. However, treatment with CTLA4 does not entirely shutdown
      the immune system; engineering animals so that the CD28-CD80/86 pathway no longer
      functions does not prevent functional protective immune responses. Thus, there
      must be yet another pathway. And there is--an "inducible T-cell costimulator"
      (ICOS) is found on T cells (activated, not naive), which has a single ligand on
      antigen-presenting cells (ICOS ligand, B7-RP-1). The rapid induction of ICOS
      speaks to its importance in T-cell function; however, ICOS is more relevant to
      the stimulation of effector and memory T cells than is CD28 signaling. There are
      similarities and differences, interactions, and overlaps between the 2 pathways,
      some of which are very useful in understanding the immunopathogenesis of immune
      diseases.

PMID- 22647860
TI  - Persistent periodontal disease hampers anti-tumor necrosis factor treatment
      response in rheumatoid arthritis.
AB  - OBJECTIVE: This study aimed to evaluate prospectively the influence and the
      evolution of periodontal disease (PD) in rheumatoid arthritis (RA) patients
      submitted to anti-tumor necrosis factor (TNF) therapy. METHODS: Eighteen patients
      with RA (according to the American College of Rheumatology criteria) were
      assessed for PD before (BL) and after 6 months (6M) of anti-TNF treatment: 15
      infliximab, 2 adalimumab, and 1 etanercept. Periodontal assessment included
      plaque and gingival bleeding indices, probing pocket depth, cementoenamel
      junction, and clinical attachment level. Rheumatologic evaluation was performed
      blinded to the dentist's assessment: demographic data, clinical manifestations,
      and disease activity (Disease Activity Score using 28 joints [DAS28], erythrocyte
      sedimentation rate [ESR], and C-reactive protein [CRP]). RESULTS: The median age
      and disease duration of patients with RA were 50 years (25-71 y) and 94% were
      female. Periodontal disease was diagnosed in 8 patients (44.4%). Comparing BL to
      6M, periodontal parameters in the entire group remained stable (P > 0.05)
      throughout the study (plaque and gingival bleeding indices, probing pocket depth,
      cementoenamel junction, and clinical attachment level), whereas an improvement in
      most analyzed RA parameters was observed in the same period: DAS28 (5.5 vs. 3.9,
      P = 0.02), ESR (21 vs. 12.5 mm/first hour, P = 0.07), and CRP (7.8 vs. 2.8 mg/dL,
      P = 0.25). Further analysis revealed that this improvement was restricted to the
      group of patients without PD (DAS28 [5.5 vs. 3.6, P = 0.04], ESR [23.0 vs. 11.5
      mm/first hour, P = 0.008], and CRP [7.4 vs. 2.1, P = 0.01]). In contrast,
      patients with PD had lack of response, with no significant differences in disease
      activity parameters between BL and 6M: DAS28 (5.2 vs. 4.4, P = 0.11), ESR (17.0
      vs. 21.0, P = 0.56), and CRP (9.0 vs. 8.8, P = 0.55). CONCLUSIONS: This study
      supports the notion that PD may affect TNF blocker efficacy in patients with RA.
      The possibility that a sustained gingival inflammatory state may hamper treatment
      response in this disease has high clinical interest because this is a treatable
      condition.

PMID- 22647861
TI  - Novel ANKH amino terminus mutation (Pro5Ser) associated with early-onset calcium
      pyrophosphate disease with associated phosphaturia.
AB  - This report describes a 32-year-old woman presenting since childhood with
      progressive calcium pyrophosphate disease (CPPD), characterized by severe
      arthropathy and chondrocalcinosis involving multiple peripheral joints and
      intervertebral disks. Because ANKH mutations have been previously described in
      familial CPPD, the proband's DNA was assessed at this locus by direct sequencing
      of promoter and coding regions and revealed 3 sequence variants in ANKH.
      Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T),
      altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of
      parental DNA revealed an identical mutation in the proband's father but not the
      mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis
      and degenerative arthropathy in the proband's father. In summary, we report a
      novel mutation, not previously described, in ANKH exon 1, wherein serine replaces
      proline, in a case of early-onset severe CPPD associated with metabolic
      abnormalities, with similar findings in the proband's father.

PMID- 22647862
TI  - Extensive skin necrosis induced by low-molecular-weight heparin in a patient with
      systemic lupus erythematosus and antiphospholipid syndrome.
AB  - Low-molecular-weight heparin-induced skin necrosis can occur as a clinical
      feature of heparin-induced thrombocytopenia syndrome. Heparin-induced
      thrombocytopenia and antiphospholipid syndromes have some clinical features in
      common, including thrombocytopenia and thrombotic events. We describe a 46-year
      old woman who developed extensive necrosis in the breast and other sites
      secondary to the use of enoxaparin after an elective hysterectomy. During the
      postoperative period, diagnoses of systemic lupus erythematosus and
      antiphospholipid syndrome were made because of some clinical and laboratory
      features (seizure, nephritis, bicytopenia, positive nuclear antibody, and
      positive antiphospholipid antibodies with a previous thrombotic event). The
      patient's clinical course improved only after corticosteroid therapy and the
      suspension of enoxaparin. Heparin-induced thrombocytopenia and antiphospholipid
      syndromes can have platelet factor 4 as a common denominator in their
      pathogenesis because platelet factor 4 tetramers can bind beta2-glycoprotein
      molecules. This case suggests that use of low-molecular-weight heparins could be
      more risky in patients with an underlying immune disease and/or could trigger
      immune reactions that must be analyzed in larger studies.

PMID- 22647863
TI  - Prevalence of musculoskeletal diseases in Guatemala, Central America: the COPCORD
      study of 2 populations.
AB  - BACKGROUND: Guatemala is a multiethnic, multilingual, and multicultural country.
      We have evaluated 2 different ethnic groups from (1) San Juan Sacatepequez County
      (SJSC), a rural population (30% illiterate), with 65% from Kaqchiquel ethnic
      group; and (2) Zone 5 of Guatemala City (Z5GC), an urban population (6.6%
      illiterate), with 95.5% mestizos. OBJECTIVE: This study aimed to measure
      simultaneously the prevalence of rheumatic diseases in these 2 Guatemalan
      populations, both located in the State of Guatemala. METHODS: A convenience
      sample of 4000 inhabitants 15 years and older was selected in each group. The
      Core Community Oriented Program for Control of Rheumatic Diseases Questionnaire
      was used in this survey. Phase 1 was for screening (identification of study
      subjects), phase 2 was for obtaining information from subjects with
      musculoskeletal complaints, and phase 3 was for rheumatologic diagnostic
      purposes. Phases 1 and 2 were performed by 6 interviewers. Phase 3 was completed
      by 4 rheumatologists. RESULTS: In phase I, 8000 subjects were identified in both
      groups. In phase II, 949 subjects reported musculoskeletal complaints: 371 (39%)
      in Z5GC and 578 (61%) in SJSC. In phase III, 419 patients were clinically
      evaluated: 141 (34%) in Z5GC and 278 (66%) in SJSC. The most prevalent
      musculoskeletal diseases were (1) osteoarthritis, (2) soft tissue rheumatism, (3)
      rheumatoid arthritis, (4) low back pain, and (5) arthralgias of unknown etiology.
      Osteoarthritis and soft tissue rheumatism were significantly more common in the
      rural population. CONCLUSIONS: The most prevalent musculoskeletal diseases in
      Guatemala seem to be similar to those in most previous Community Oriented Program
      for Control of Rheumatic Diseases studies. Most subjects were still working.
      Further studies examining medical care received and impact on function can now be
      of interest.

PMID- 22647864
TI  - Acute crystalline arthritis in an artificial knee.

PMID- 22647865
TI  - A life-threatening central nervous system-tuberculosis inflammatory reaction
      nonresponsive to corticosteroids and successfully controlled by infliximab in a
      young patient with a variant of juvenile idiopathic arthritis.
AB  - We report a young patient with a variant of juvenile idiopathic arthritis, who,
      after 4 years of infliximab treatment, developed miliary tuberculosis (TB) with
      central nervous system involvement (meningitis and multiple tuberculomas). After
      anti-TB treatment, clinical and radiologic responses were observed, but severe
      cerebrospinal fluid and brain inflammatory reaction, nonresponsive to
      corticosteroids, persisted. It was considered a life-threatening paradoxical
      reaction based on initial cerebrospinal fluid isolation of Mycobacterium
      tuberculosis fully sensitive to primary anti-TB drugs. After 4 months in the
      hospital, infliximab was administered considering that infliximab is a potent
      tumor necrosis factor alpha inhibiting agent that participates in the formation
      and preservation of granulomas and may help to modulate the exaggerated cell
      mediated immune response against mycobacterial antigens. Clinical complications
      associated to brain inflammation resolved, and after 3 years of follow-up, the
      patient remains self-sufficient without neurologic sequels.

PMID- 22647866
TI  - Charcot knee secondary to lumbar spinal cord syringomyelia: complication of
      spinal anesthesia.

PMID- 22647868
TI  - Sun exposure and the use of sunscreen among rheumatology inflammatory arthropathy
      patients receiving anti-tumor necrosis factor therapy.

PMID- 22647867
TI  - Satisfaction and access to clinical care in a rheumatology clinic at a large
      urban medical center.

PMID- 22647869
TI  - Outcome of treatment after first relapse in younger adults with acute myeloid
      leukemia initially treated by the ALFA-9802 trial.
AB  - Forty-seven percent of adults with acute myeloid leukemia (AML) who entered the
      ALFA-9802 trial and achieved a first complete remission (CR) experienced a first
      relapse. We examined the outcome of these 190 adult patients. Eighty-four
      patients (44%) achieved a second CR. The median overall survival (OS) after
      relapse was 8.9 months with a 2-year OS at 25%. Factors predicting a better
      outcome after relapse were stem cell transplant (SCT) performed in second CR and
      a first CR duration >1 year. Risk groups defined at the time of diagnosis and
      treatment received in first CR also influenced the outcome after relapse. The
      best results were obtained in patients with core binding factor (CBF)-AML, while
      patients initially defined as favorable intermediate risk showed a similar
      outcome after relapse than those initially entering the poor risk group. We
      conclude that most adult patients with recurring AML could not be rescued using
      current available therapies, although allogeneic SCT remains the best therapeutic
      option at this stage of the disease.

PMID- 22647872
TI  - Prevention and management of ovarian hyperstimulation syndrome.
AB  - Ovarian hyperstimulation syndrome is a relatively common complication of ovarian
      stimulation and can be life-threatening. The pathophysiology of ovarian
      hyperstimulation syndrome is characterised by increased capillary permeability,
      leading to leakage of fluid from the vascular compartment, with third space fluid
      accumulation and intravascular dehydration. The combined use of a gonadotrophin
      releasing hormone antagonist protocol with gonadotrophin-releasing hormone
      agonist triggering and oocyte and embryo freezing has considerable promise in
      preventing ovarian hyperstimulation syndrome. Women with severe ovarian
      hyperstimulation syndrome require hospitalisation for more careful monitoring and
      treatment. Transvaginal paracentesis can be used as an outpatient treatment to
      prevent the need for hospitalisation. The inhibition of vascular permeability
      seems to be a novel therapeutic approach to preventing and treating ovarian
      hyperstimulation syndrome.

PMID- 22647870
TI  - Identification of new autoantigens for primary biliary cirrhosis using human
      proteome microarrays.
AB  - Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown
      etiology and is considered to be an autoimmune disease. Autoantibodies are
      important tools for accurate diagnosis of PBC. Here, we employed serum profiling
      analysis using a human proteome microarray composed of about 17,000 full-length
      unique proteins and identified 23 proteins that correlated with PBC. To validate
      these results, we fabricated a PBC-focused microarray with 21 of these newly
      identified candidates and nine additional known PBC antigens. By screening the
      PBC microarrays with additional cohorts of 191 PBC patients and 321 controls (43
      autoimmune hepatitis, 55 hepatitis B virus, 31 hepatitis C virus, 48 rheumatoid
      arthritis, 45 systematic lupus erythematosus, 49 systemic sclerosis, and 50
      healthy), six proteins were confirmed as novel PBC autoantigens with high
      sensitivities and specificities, including hexokinase-1 (isoforms I and II),
      Kelch-like protein 7, Kelch-like protein 12, zinc finger and BTB domain
      containing protein 2, and eukaryotic translation initiation factor 2C, subunit 1.
      To facilitate clinical diagnosis, we developed ELISA for Kelch-like protein 12
      and zinc finger and BTB domain-containing protein 2 and tested large cohorts (297
      PBC and 637 control sera) to confirm the sensitivities and specificities observed
      in the microarray-based assays. In conclusion, our research showed that a
      strategy using high content protein microarray combined with a smaller but more
      focused protein microarray can effectively identify and validate novel PBC
      specific autoantigens and has the capacity to be translated to clinical diagnosis
      by means of an ELISA-based method.

PMID- 22647871
TI  - A novel strategy for global analysis of the dynamic thiol redox proteome.
AB  - Nitroxidative stress in cells occurs mainly through the action of reactive
      nitrogen and oxygen species (RNOS) on protein thiol groups. Reactive nitrogen and
      oxygen species-mediated protein modifications are associated with
      pathophysiological states, but can also convey physiological signals.
      Identification of Cys residues that are modified by oxidative stimuli still poses
      technical challenges and these changes have never been statistically analyzed
      from a proteome-wide perspective. Here we show that GELSILOX, a method that
      combines a robust proteomics protocol with a new computational approach that
      analyzes variance at the peptide level, allows a simultaneous analysis of dynamic
      alterations in the redox state of Cys sites and of protein abundance. GELSILOX
      permits the characterization of the major endothelial redox targets of hydrogen
      peroxide in endothelial cells and reveals that hypoxia induces a significant
      increase in the status of oxidized thiols. GELSILOX also detected thiols that are
      redox-modified by ischemia-reperfusion in heart mitochondria and demonstrated
      that these alterations are abolished in ischemia-preconditioned animals.

PMID- 22647873
TI  - Role of reproductive surgery in the era of assisted reproductive technology.
AB  - Reproductive surgery could be divided into surgery as a primary treatment for
      infertility, surgery to enhance in-vitro fertilisation outcome, and surgery for
      fertility preservation. A shift has occurred away from surgery as a primary
      treatment of infertility to surgery playing a crucial part in enhancing in-vitro
      fertilisation outcome and for fertility preservation. A normal uterine cavity is
      a prerequisite for implantation, and hysteroscopic correction of intrauterine
      pathology, including polypectomy, myomectomy and metroplasty, increases the
      chances of having a successful pregnancy. Management of hydrosalpinx before in
      vitro fertilisation treatment by laparoscopic salpingectomy or proximal tubal
      occlusion increases the in-vitro fertilisation delivery rate. Finally, surgery
      plays an important role in preservation of fertility. This includes laparoscopic
      ovarian transposition, ovarian tissue removal for cryopreservation and ovarian
      transplantation.

PMID- 22647874
TI  - NKT and MAIT invariant TCRalpha sequences can be produced efficiently by VJ gene
      recombination.
AB  - Semi-invariant T cell receptors (TCRs) found on natural killer T (NKT) and
      mucosal-associated invariant T (MAIT) cells are characterized by the use of
      invariant variable (V) and joining (J) gene combinations in the TCR alpha-chain,
      as well as ubiquitous canonical TCRalpha amino acid sequences that are dominant
      in many individuals and similar across species. That they are so prevalent
      indicates that they occupy an important niche within the immune system. However,
      these TCRs are produced by a largely random gene recombination process, which
      seems a risky approach for the immune system to acquire these innate-like cells.
      We surveyed studies reporting NKT and MAIT TCRalpha sequences for six and four
      different species, respectively. Although the germline nature of the canonical
      human and mouse NKT and mouse MAIT TCRalpha sequences and an overlap of
      nucleotides between the mouse MAIT-related Valpha and Jalpha genes have been
      noted in previous studies, in this study we demonstrate that, for all reported
      species, the canonical TCRalpha amino acid sequences can be encoded by at least
      one germline-derived nucleotide sequence. Moreover, these nucleotide sequences
      can utilize an overlap between the Valpha and Jalpha genes in their production,
      which enables them to be produced by a large variety of recombination mechanisms.
      We investigated the role of these TCRalpha features in the production of the
      canonical NKT and MAIT TCRalpha sequences. In computer simulations of a random
      recombination process involving the invariant NKT and MAIT TCRalpha gene
      combinations for each species, the canonical NKT and MAIT TCRalpha sequences were
      the first or second most generated of all sequences with the CDR3alpha length
      restrictions associated with NKT and MAIT cells. These results suggest that the
      immune machinery enables the canonical NKT and MAIT TCRalpha sequences to be
      produced with great efficiency through the process of convergent recombination,
      ensuring their prevalence across individuals and species.

PMID- 22647875
TI  - Impaired skeletal muscle blood flow control with advancing age in humans:
      attenuated ATP release and local vasodilation during erythrocyte deoxygenation.
AB  - RATIONALE: Skeletal muscle blood flow is coupled with the oxygenation state of
      hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor
      and releases ATP during deoxygenation to evoke vasodilation. Whether this
      function is impaired in humans of advanced age is unknown. OBJECTIVE: To test the
      hypothesis that older adults demonstrate impaired muscle blood flow and lower
      intravascular ATP during conditions of erythrocyte deoxygenation. METHODS AND
      RESULTS: We showed impaired forearm blood flow responses during 2 conditions of
      erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with
      age, which was caused by reduced local vasodilation. In young adults, both
      hypoxia and exercise significantly increased venous [ATP] and ATP effluent
      (forearm blood flow*[ATP]) draining the skeletal muscle. In contrast, hypoxia and
      exercise did not increase venous [ATP] in older adults, and both venous [ATP] and
      ATP effluent were substantially reduced compared with young people despite
      similar levels of deoxygenation. Next, we demonstrated that this could not be
      explained by augmented extracellular ATP hydrolysis in whole blood with age.
      Finally, we found that deoxygenation-mediated ATP release from isolated
      erythrocytes was essentially nonexistent in older adults. CONCLUSIONS: Skeletal
      muscle blood flow during conditions of erythrocyte deoxygenation was markedly
      reduced in aging humans, and reductions in plasma ATP and erythrocyte-mediated
      ATP release may be a novel mechanism underlying impaired vasodilation and oxygen
      delivery during hypoxemia with advancing age. Because aging is associated with
      elevated risk for ischemic cardiovascular disease and exercise intolerance,
      interventions that target erythrocyte-mediated ATP release may offer therapeutic
      potential.

PMID- 22647876
TI  - Epistatic rescue of Nkx2.5 adult cardiac conduction disease phenotypes by
      prospero-related homeobox protein 1 and HDAC3.
AB  - RATIONALE: Nkx2.5 is one of the most widely studied cardiac-specific
      transcription factors, conserved from flies to man, with multiple essential roles
      in both the developing and adult heart. Specific dominant mutations in NKX2.5
      have been identified in adult congenital heart disease patients presenting with
      conduction system anomalies and recent genome-wide association studies implicate
      the NKX2.5 locus, as causative for lethal arrhythmias ("sudden cardiac death")
      that occur at a frequency in the population of 1 in 1000 per annum worldwide.
      Haploinsufficiency for Nkx2.5 in the mouse phenocopies human conduction disease
      pathology yet the phenotypes, described in both mouse and man, are highly
      pleiotropic, implicit of unknown modifiers and/or factors acting in epistasis
      with Nkx2.5/NKX2.5. OBJECTIVE: To identify bone fide upstream genetic modifier(s)
      of Nkx2.5/NKX2.5 function and to determine epistatic effects relevant to the
      manifestation of NKX2.5-dependent adult congenital heart disease. METHODS AND
      RESULTS: A study of cardiac function in prospero-related homeobox protein 1
      (Prox1) heterozygous mice, using pressure-volume loop and micromannometry,
      revealed rescue of hemodynamic parameters in Nkx2.5(Cre/+); Prox1(loxP/+) animals
      versus Nkx2.5(Cre/+) controls. Anatomic studies, on a Cx40(EGFP) background,
      revealed Cre-mediated knock-down of Prox1 restored the anatomy of the
      atrioventricular node and His-Purkinje network both of which were severely
      hypoplastic in Nkx2.5(Cre/+) littermates. Steady state surface
      electrocardiography recordings and high-speed multiphoton imaging, to assess
      Ca(2+) handling, revealed atrioventricular conduction and excitation-contraction
      were also normalized by Prox1 haploinsufficiency, as was expression of conduction
      genes thought to act downstream of Nkx2.5. Chromatin immunoprecipitation on adult
      hearts, in combination with both gain and loss-of-function reporter assays in
      vitro, revealed that Prox1 recruits the corepressor HDAC3 to directly repress
      Nkx2.5 via a proximal upstream enhancer as a mechanism for regulating Nkx2.5
      function in adult cardiac conduction. CONCLUSIONS: Here we identify Prox1 as a
      direct upstream modifier of Nkx2.5 in the maintenance of the adult conduction
      system and rescue of Nkx2.5 conduction disease phenotypes. This study is the
      first example of rescue of Nkx2.5 function and establishes a model for ensuring
      electrophysiological function within the adult heart alongside insight into a
      novel Prox1-HDAC3-Nkx2.5 signaling pathway for therapeutic targeting in
      conduction disease.

PMID- 22647877
TI  - Myofilament Ca sensitization increases cytosolic Ca binding affinity, alters
      intracellular Ca homeostasis, and causes pause-dependent Ca-triggered arrhythmia.
AB  - RATIONALE: Ca binding to the troponin complex represents a major portion of
      cytosolic Ca buffering. Troponin mutations that increase myofilament Ca
      sensitivity are associated with familial hypertrophic cardiomyopathy and confer a
      high risk for sudden death. In mice, Ca sensitization causes ventricular
      arrhythmias, but the underlying mechanisms remain unclear. OBJECTIVE: To test the
      hypothesis that myofilament Ca sensitization increases cytosolic Ca buffering and
      to determine the resulting arrhythmogenic changes in Ca homeostasis in the intact
      mouse heart. METHODS AND RESULTS: Using cardiomyocytes isolated from mice
      expressing troponin T (TnT) mutants (TnT-I79N, TnT-F110I, TnT-R278C), we found
      that increasing myofilament Ca sensitivity produced a proportional increase in
      cytosolic Ca binding. The underlying cause was an increase in the cytosolic Ca
      binding affinity, whereas maximal Ca binding capacity was unchanged. The effect
      was sufficiently large to alter Ca handling in intact mouse hearts at
      physiological heart rates, resulting in increased end-diastolic [Ca] at fast
      pacing rates, and enhanced sarcoplasmic reticulum Ca content and release after
      pauses. Accordingly, action potential (AP) regulation was altered, with postpause
      action potential prolongation, afterdepolarizations, and triggered activity.
      Acute Ca sensitization with EMD 57033 mimicked the effects of Ca-sensitizing TnT
      mutants and produced pause-dependent ventricular ectopy and sustained ventricular
      tachycardia after acute myocardial infarction. CONCLUSIONS: Myofilament Ca
      sensitization increases cytosolic Ca binding affinity. A major proarrhythmic
      consequence is a pause-dependent potentiation of Ca release, action potential
      prolongation, and triggered activity. Increased cytosolic Ca binding represents a
      novel mechanism of pause-dependent arrhythmia that may be relevant for inherited
      and acquired cardiomyopathies.

PMID- 22647878
TI  - Relationship between motor recovery and independence after sensorimotor-complete
      cervical spinal cord injury.
AB  - BACKGROUND: For therapeutics directed to the injured spinal cord, a change in
      neurological impairment has been proposed as a relevant acute clinical study end
      point. However, changes in neurological function, even if statistically
      significant, may not be associated with a functional impact, such as a meaningful
      improvement in items within the self-care subscore of the Spinal Cord
      Independence Measure (SCIM). OBJECTIVE: The authors examined the functional
      significance associated with spontaneously recovering upper-extremity motor
      function after sensorimotor-complete cervical spinal cord injury (SCI). METHODS:
      Using the European Multi-center Study about Spinal Cord Injury (EMSCI) data set,
      a retrospective analysis was undertaken of individuals with cervical sensorimotor
      complete SCI (initial motor level, C4-C7). Specifically, changes in upper
      extremity motor score (UEMS), motor level, and SCIM (total and self-care
      subscore) were assessed between approximately 1 and 48 weeks after injury (n =
      74). RESULTS: The initial motor level did not significantly influence the total
      UEMS recovered or number of motor levels recovered. SCIM self-care subscore
      recovery was significantly greater for those individuals regaining 2 motor levels
      compared with those recovering only 1 or no motor levels. However, the recovery
      in the SCIM self-care subscore was not significantly different between
      individuals recovering only 1 motor level and those individuals who showed no
      motor-level improvement. CONCLUSIONS: A 2 motor-level improvement indicates a
      clinically meaningful change and might be considered a primary outcome in acute
      and subacute interventional trials enrolling individuals with cervical
      sensorimotor-complete SCI.

PMID- 22647879
TI  - Movement kinematics during a drinking task are associated with the activity
      capacity level after stroke.
AB  - BACKGROUND: Kinematic analysis is a powerful method for an objective assessment
      of movements and is increasingly used as an outcome measure after stroke. Little
      is known about how the actual movement performance measured with kinematics is
      related to the common traditional assessment scales. The aim of this study was to
      determine the relationships between movement kinematics from a drinking task and
      the impairment or activity limitation level after stroke. METHODS: Kinematic
      analysis of movement performance in a drinking task was used to measure movement
      time, smoothness, and angular velocity of elbow and trunk displacement (TD) in 30
      individuals with stroke. Sensorimotor impairment was assessed with the Fugl-Meyer
      Assessment (FMA), activity capacity limitation with the Action Research Arm Test
      (ARAT), and self-perceived activity difficulties with the ABILHAND questionnaire.
      RESULTS: Backward multiple regression revealed that the movement smoothness
      (similarly to movement time) and TD together explain 67% of the total variance in
      ARAT. Both variables uniquely contributed 37% and 11%, respectively. The TD alone
      explained 20% of the variance in the FMA, and movement smoothness explained 6% of
      the variance in the ABILHAND. CONCLUSIONS: The kinematic movement performance
      measures obtained during a drinking task are more strongly associated with
      activity capacity than with impairment. The movement smoothness and time,
      possibly together with compensatory movement of the trunk, are valid measures of
      activity capacity and can be considered as key variables in the evaluation of
      upper-extremity function after stroke. This increased knowledge is of great value
      for better interpretation and application of kinematic data in clinical studies.

PMID- 22647880
TI  - Biomarkers for detection and prognosis of breast cancer identified by a
      functional hypermethylome screen.
AB  - Breast cancer (BC) is a disease with diverse tumor heterogeneity, which
      challenges conventional approaches to develop biomarkers for early detection and
      prognosis. To identify effective biomarkers, we performed a genome-wide screen
      for functional methylation changes in BC, i.e., genes silenced by promoter
      hypermethylation, using a functionally proven gene expression approach. A subset
      of candidate hypermethylated genes were validated in primary BCs and tested as
      markers for detection and prognosis prediction of BC. We identified 33 cancer
      specific methylated genes and, among these, two categories of genes: (1) highly
      frequent methylated genes that detect early stages of BC. Within that category,
      we have identified the combination of NDRG2 and HOXD1 as the most sensitive (94%)
      and specific (90%) gene combination for detection of BC; (2) genes that show
      stage dependent methylation frequency pattern, which are candidates to help
      delineate BC prognostic signatures. For this category, we found that methylation
      of CDO1, CKM, CRIP1, KL and TAC1 correlated with clinical prognostic variables
      and was a significant prognosticator for poor overall survival in BC patients.
      CKM [Hazard ratio (HR) = 2.68] and TAC1 (HR = 7.73) were the strongest single
      markers and the combination of both (TAC1 and CKM) was associated with poor
      overall survival independent of age and stage in our training (HR = 1.92) and
      validation cohort (HR = 2.87). Our study demonstrates an efficient method to
      utilize functional methylation changes in BC for the development of effective
      biomarkers for detection and prognosis prediction of BC.

PMID- 22647881
TI  - Substrate analog studies of the omega-regiospecificity of Mycobacterium
      tuberculosis cholesterol metabolizing cytochrome P450 enzymes CYP124A1, CYP125A1
      and CYP142A1.
AB  - We report the synthesis and evaluation of a series of cholesterol side-chain
      analogs as mechanistic probes of three important Mycobacterium tuberculosis
      cytochrome P450 enzymes that selectively oxidize the omega-position of the methyl
      branched cholesterol side-chain. To probe the structural requirements for the
      thermodynamically disfavored omega-regiospecificity we compared the binding of
      these substrate analogs to each P450, determined the turnover rates, and
      characterized the enzymatic products. The results are discussed in the context of
      the structure-activity relationships of the enzymes and how their active sites
      enforce omega-oxidation.

PMID- 22647882
TI  - The effects of Castanospermine, an oligosaccharide processing inhibitor, on
      mononuclear/endothelial cell binding and the expression of cell adhesion
      molecules.
AB  - INTRODUCTION: In this study we aimed to determine whether Castanospermine, a
      transplant immunosuppressive agent, impaired mononuclear/endothelial cell binding
      and expression of their cell adhesion molecules. METHODS: The binding of human
      umbilical vein endothelial cells with peripheral blood mononuclear cells was
      measured by a binding assay using Chromium 51 label; the membrane expression of
      cell adhesion molecules was measured by flow cytometry expressed as mean
      fluorescence intensity ratios. RESULTS: Castanospermine decreased
      mononuclear/endothelial cell binding if and only if both cell types were treated
      with Castanospermine: this impairment occurred if endothelial cells were treated
      with a range of doses of Castanospermine and mononuclear cells were treated with
      a constant dose of Castanospermine (p<0.001 versus untreated p=0.978) or vice
      versa (p=0.004 versus untreated p=0.582). Upon human umbilical vein endothelial
      cells Castanospermine reduced the mean fluorescence intensity ratios of E
      selectin (p=0.003), ICAM-1 (p<0.001), ICAM-2 (p=0.004) and PECAM-1 (p<0.001) but
      increased it for P-selectin (p<0.001). Upon peripheral blood mononuclear cells
      Castanospermine reduced the mean fluorescence intensity ratios of L-selectin
      (P<0.001), LFA-1alpha (p<0.001), VLA-4 (p<0.001), Mac-1 (P<0.001) and CR4
      (p<0.001) but increased the mean fluorescence intensity ratios of PSGL-1
      (p<0.001) and PECAM-1 (p=0.001). Similar changes in mean fluorescence intensity
      ratios were found in the subset of lymphocytes and monocytes but the reductions
      in LFA-1alpha and VLA-4 on lymphocytes and Mac-1 and CR4 on monocytes were
      greater. CONCLUSIONS: The reduction in mononuclear/endothelial cell binding
      mediated by CAST and the reduction in expression of multiple cell adhesion
      molecules on these cell types help to explain the mechanism of its established
      immunosuppressive effect.

PMID- 22647884
TI  - Investigation of antibodies against synaptic proteins in a cross-sectional cohort
      of psychotic patients.

PMID- 22647883
TI  - Longitudinal progression of frontal and temporal lobe changes in schizophrenia.
AB  - Cortical abnormalities are considered a neurobiological characteristic of
      schizophrenia. However, the pattern of such deficits as they progress over the
      illness remains poorly understood. The goal of this project was to assess the
      progression of cortical thinning in frontal and temporal cortical regions in
      schizophrenia, and determine whether relationships exist between them and
      neuropsychological and clinical symptom profiles. As part of a larger
      longitudinal 2-year follow-up study, schizophrenia (n=20) and healthy
      participants (n=20) group-matched for age, gender, and recent-alcohol use, were
      selected. Using MRI, estimates of gray matter thickness were derived from primary
      anatomical gyri of the frontal and temporal lobes using surface-based algorithms.
      These values were entered into repeated-measures analysis of variance models to
      determine group status and time effects. Change values in cortical regions were
      correlated with changes in neuropsychological functioning and clinical
      symptomatology. Results revealed exaggerated cortical thinning of the middle
      frontal, superior temporal, and middle temporal gyri in schizophrenia
      participants. These thickness changes strongly influenced volumetric reductions,
      but were not related to shrinking surface area. Neuropsychological and clinical
      symptom profiles were stable in the schizophrenia participants despite these
      neuroanatomic changes. Overall it appears that ongoing abnormalities in the
      cerebral cortex continue after initial onset of schizophrenia, particularly the
      lateral aspects of frontal and temporal regions, and do not relate to
      neuropsychological or clinical measures over time. Maintenance of
      neuropsychological performance and clinical stability in the face of changing
      neuroanatomical structure suggests the involvement of alternative compensatory
      mechanisms.

PMID- 22647885
TI  - Slippage and nanorheology of thin liquid polymer films.
AB  - Thin liquid films on surfaces are part of our everyday life; they serve, e.g., as
      coatings or lubricants. The stability of a thin layer is governed by interfacial
      forces, described by the effective interface potential, and has been subject of
      many studies in recent decades. In recent years, the dynamics of thin liquid
      films has come into focus since results on the reduction of the glass transition
      temperature raised new questions on the behavior of especially polymeric liquids
      in confined geometries. The new focus was fired by theoretical models that
      proposed significant implication of the boundary condition at the solid/liquid
      interface on the dynamics of dewetting and the form of a liquid front. Our study
      reflects these recent developments and adds new experimental data to corroborate
      the theoretical models. To probe the solid/liquid boundary condition
      experimentally, different methods are possible, each bearing advantages and
      disadvantages, which will be discussed. Studying liquid flow on a variety of
      different substrates entails a view on the direct implications of the substrate.
      The experimental focus of this study is the variation of the polymer chain
      length; the results demonstrate that inter-chain entanglements and in particular
      their density close to the interface, originating from non-bulk conformations,
      govern the liquid slip of a polymer.

PMID- 22647886
TI  - Low placental growth factor across pregnancy identifies a subset of women with
      preterm preeclampsia: type 1 versus type 2 preeclampsia?
AB  - Preeclampsia is a heterogeneous syndrome affecting 3% to 5% of all pregnancies.
      An imbalance of the antiangiogenic and proangiogenic factors, soluble receptor
      fms-like tyrosine kinase 1 and placental growth factor (PGF), is thought to
      contribute to the pathophysiology of preeclampsia. Maternal plasma PGF and
      soluble receptor fms-like tyrosine kinase 1 were quantified by specific
      immunoassays in cross-sectional samples from 130 preeclamptic subjects and 342
      normotensive controls at delivery and longitudinally in samples from 50 women who
      developed preeclampsia and 250 normotensive controls. Among women who developed
      preeclampsia, 46% (n=23) evidenced a pattern of consistently low maternal PGF
      across pregnancy below the lower 95% CI of controls from 15 weeks' gestation to
      term. In contrast, the remaining 54% (n=27) of women who developed preeclampsia
      had maternal PGF concentrations similar to or above (n=7) those of normotensive
      controls. Subjects with low PGF across pregnancy who developed preeclampsia
      evidenced significantly higher blood pressure in early pregnancy (P<0.05) and,
      after diagnosis, earlier gestational age at delivery (P<0.05) and more preterm
      birth (P<0.05) compared with preeclamptic patients with high PGF. A significant
      subset of women who develop preeclampsia show evidence of consistently low PGF
      across pregnancy. Low PGF with preeclampsia was associated with preterm delivery
      compared with preeclamptic patients with high PGF. Identifying women with
      consistently low plasma PGF during pregnancy may provide a greater understanding
      of preeclampsia pathophysiology and may provide more focused research and
      clinical activities.

PMID- 22647888
TI  - The association between orthostatic hypotension and nocturnal blood pressure may
      explain the risk for heart failure.

PMID- 22647887
TI  - Activation of Nod-like receptor protein 3 inflammasomes turns on podocyte injury
      and glomerular sclerosis in hyperhomocysteinemia.
AB  - Inflammasome is a multiprotein complex consisting of Nod-like receptor protein 3
      (NALP3), apoptosis-associated speck-like protein (ASC), and caspase 1 or 5, which
      functions to switch on the inflammatory process. The present study hypothesized
      that the formation and activation of NALP3 inflammasomes turn on podocyte injury
      leading to glomerulosclerosis during hyperhomocysteinemia (hHcys). RT-PCR and
      Western blot analysis demonstrated that murine podocytes expressed 3 essential
      components of the NALP3 inflammasome complex, namely, NALP3, ASC, and caspase 1.
      Treatment of podocytes with l-homocysteine induced the formation of NALP3
      inflammasome complex, an increase in caspase 1 activity, podocyte cytoskeleton
      rearrangement, and decreased production of vascular endothelial growth factor
      from podocytes, which were all blocked by silencing the ASC gene or inhibiting
      caspase 1 activity. In mice with hHcys induced by feeding them a folate-free
      diet, NALP3 inflammasome formation and activation in glomerular podocytes were
      detected at an early stage, as shown by confocal microscopy, size exclusion
      chromatography of the assembled inflammasome complex, and increased interleukin
      1beta production in glomeruli. Locally silencing the ASC gene in the kidney
      significantly reduced NALP3 inflammasome formation and interleukin 1beta
      production in glomeruli of mice with hHcys. Pathologically, hHcys-associated
      albuminuria, foot process effacement of podocytes, loss of podocyte slit
      diaphragm molecules, and glomerulosclerosis at the late stage were significantly
      improved by local ASC gene silencing or by caspase 1 inhibition. In conclusion,
      NALP3 inflammasome formation and activation on stimulation of homocysteine are
      important molecular mechanisms triggering podocyte injury and ultimately
      resulting in glomerulosclerosis in hHcys.

PMID- 22647889
TI  - Hypertension in aortic stenosis: implications for left ventricular structure and
      cardiovascular events.
AB  - The impact of hypertension on left ventricular structure and outcome during
      progression of aortic valve stenosis has not been reported from a large
      prospective study. Data from 1616 patients with asymptomatic aortic stenosis
      randomized to placebo-controlled treatment with combined simvastatin and
      ezetimibe in the Simvastatin Ezetimibe in Aortic Stenosis Study were used. The
      primary study end point included combined cardiovascular death, aortic valve
      events, and ischemic cardiovascular events. Hypertension was defined as history
      of hypertension or elevated baseline blood pressure. Left ventricular hypertrophy
      was defined as left ventricular mass/height(2.7) >= 46.7 g/m(2.7) in women and >=
      49.2 g/m(2.7) in men and concentric geometry as relative wall thickness >= 0.43.
      Baseline peak aortic jet velocity and aortic stenosis progression rate did not
      differ between hypertensive (n = 1340) and normotensive (n = 276) patients.
      During 4.3 years of follow-up, the prevalence of concentric left ventricular
      hypertrophy increased 3 times in both groups. Hypertension predicted 51% higher
      incidence of abnormal LV geometry at final study visit independent of other
      confounders (P<0.01). In time-varying Cox regression, hypertension did not
      predict increased rate of the primary study end point. However, hypertension was
      associated with a 56% higher rate of ischemic cardiovascular events and a 2-fold
      increased mortality (both P<0.01), independent of aortic stenosis severity,
      abnormal left ventricular geometry, in-treatment systolic blood pressure, and
      randomized study treatment. No impact on aortic valve replacement was found. In
      conclusion, among patients with initial asymptomatic mild-to-moderate aortic
      stenosis, hypertension was associated with more abnormal left ventricular
      structure and increased cardiovascular morbidity and mortality.

PMID- 22647890
TI  - Rapid onset of renal sympathetic nerve activation in rabbits fed a high-fat diet.
AB  - Hypertension and elevated sympathetic drive result from consumption of a high
      calorie diet and deposition of abdominal fat, but the etiology and temporal
      characteristics are unknown. Rabbits instrumented for telemetric recording of
      arterial pressure and renal sympathetic nerve activity (RSNA) were fed a high-fat
      diet for 3 weeks then control diet for 1 week or control diet for 4 weeks.
      Baroreflexes and responses to air-jet stress and hypoxia were determined weekly.
      After 1 week of high-fat diet, caloric intake increased by 62%, accompanied by
      elevated body weight, blood glucose, plasma insulin, and leptin (8%, 14%, 134%,
      and 252%, respectively). Mean arterial pressure, heart rate, and RSNA also
      increased after 1 week (6%, 11%, and 57%, respectively). Whereas mean arterial
      pressure and body weight continued to rise over 3 weeks of high-fat diet, heart
      rate and RSNA did not change further. The RSNA baroreflex was attenuated from the
      first week of the diet. Excitatory responses to air-jet stress diminished over 3
      weeks of high-fat diet, but responses to hypoxia were invariant. Resumption of a
      normal diet returned glucose, insulin, leptin, and heart rate to control levels,
      but body weight, mean arterial pressure, and RSNA remained elevated. In
      conclusion, elevated sympathetic drive and impaired baroreflex function, which
      occur within 1 week of consumption of a high-fat, high-calorie diet, appear
      integral to the rapid development of obesity-related hypertension. Increased
      plasma leptin and insulin may contribute to the initiation of hypertension but
      are not required for maintenance of mean arterial pressure, which likely lies in
      alterations in the response of neurons in the hypothalamus.

PMID- 22647891
TI  - With a pinch of salt: does reduced dietary sodium consumption promote
      atherosclerosis?

PMID- 22647892
TI  - Activation of the Renin-Angiotensin system mediates the effects of dietary salt
      intake on atherogenesis in the apolipoprotein E knockout mouse.
AB  - Dietary salt intake is a major determinant of the activation state of renin
      angiotensin-aldosterone system. Given the important role of the renin-angiotensin
      aldosterone system in plaque accumulation, we investigated its role in the
      development of atherogenesis associated with sodium intake in apolipoprotein E
      knockout mice. Six-weeks of a low-salt diet (containing 0.03% sodium) resulted in
      a 4-fold increase in plaque accumulation in apolipoprotein E knockout mice when
      compared with mice receiving normal chow (containing 0.30% sodium). This was
      associated with activation of the renin-angiotensin-aldosterone system, increased
      vascular expression of adhesion molecules and inflammatory cytokines, and
      increased adhesion of labeled leukocytes across the whole aorta on a dynamic flow
      assay. These changes were blocked with the angiotensin-converting enzyme
      inhibitor perindopril (2 mg/kg per day). A high-salt diet (containing 3% sodium)
      attenuated vascular inflammation and atherogenesis, associated with suppression
      of the renin-angiotensin-aldosterone system, although systolic blood pressure
      levels were modestly increased (5 +/- 1 mmHg). Constitutive activation of the
      renin-angiotensin-aldosterone system in angiotensin-converting enzyme 2
      apolipoprotein E knockout mice was also associated with increased atherosclerosis
      and vascular adhesion, and this was attenuated by a high-salt diet associated
      with suppression of the renin-angiotensin-aldosterone system. By contrast, a low
      salt diet failed to further activate the renin-angiotensin-aldosterone system or
      to increase atherosclerosis in angiotensin-converting enzyme 2 apolipoprotein E
      knockout mice. Together, these data validate a relationship between salt-mediated
      renin-angiotensin-aldosterone system activation and atherogenesis, which may
      partly explain the inconclusive or paradoxical findings of recent observational
      studies, despite clear effects on blood pressure.

PMID- 22647893
TI  - Effects of a facial nerve lesion on responses in forehead microvessels to
      conjunctival irritation and paced breathing.
AB  - To investigate parasympathetic influences on the forehead microvasculature, blood
      flow was monitored bilaterally in seven participants with a unilateral facial
      nerve lesion during conjunctival irritation with Schirmer's strips and while
      breathing at 0.15 Hz. Blood flow and slow-wave frequency increased on the intact
      side of the forehead during Schirmer's test but did not change on the denervated
      side. However, a 0.15 Hz vascular wave strengthened during paced breathing,
      particularly on the denervated side. These findings indicate that parasympathetic
      activity in the facial nerve increases forehead blood flow during minor
      conjunctival irritation, but may interfere with the 0.15 Hz vascular wave.

PMID- 22647894
TI  - Two cases of spontaneous temporal encephalocele.
AB  - This is a report of two cases of spontaneous temporal encephalocele: one was
      anteroinferior and presented with epilepsy; the other was posteroinferior and
      presented with facial neuritis and labyrinthitis. Spontaneous temporal
      encephalocele is relatively rare and apparently not familiar to a majority of
      primary physicians. It may present with a variety of symptoms according to its
      anatomical location, including cerebrospinal fluid fistulas, recurrent
      meningitis, chronic otitis media, hearing loss, facial nerve palsy and medically
      intractable epilepsy. Attention should be paid to this disease entity, as it is
      easily overlooked in imaging studies and can leave serious neurological deficits.

PMID- 22647895
TI  - Frustrated Lewis pair addition to conjugated diynes: formation of zwitterionic
      1,2,3-butatriene derivatives.
AB  - The frustrated Lewis pair B(C(6)F(5))(3)/P(o-tolyl)(3) (4a) reacts with 4,6
      decadiyne to give the trans-1,2-addition product 5. In contrast, the
      B(C(6)F(5))(3)/P(t)Bu(3) FLP (4b) reacts with this substrate to give the trans
      1,4-adduct trans-6. The cumulene trans-6 undergoes trans-/cis-isomerization upon
      photolysis to give a ca. 1:1 trans-6/cis-6 mixture. The FLP 4b reacts with 2,6
      hexadiyne at r.t. to yield a ca. 4:1 mixture of their trans-1,2- and trans-1,4
      addition products (7,8). DFT calculations showed that the zwitterionic 1,4
      addition products are favored under thermodynamic control. Thermolysis of the
      kinetic trans-1,2-addition product (7) (80  degrees C, bromobenzene) does not
      lead to the thermodynamically favored 1,4-isomer (8), but instead elimination of
      isobutylene occurs to the formal trans-1,2-adduct (9) of the
      B(C(6)F(5))(3)/PH(t)Bu(2) pair. Compounds 5, 6, 7, 8, 9 were analyzed by X-ray
      diffraction.

PMID- 22647896
TI  - The effect of funded varicella immunization programs on varicella-related
      hospitalizations in IMPACT centers, Canada, 2000-2008.
AB  - BACKGROUND: The 12 Immunization Monitoring Program, Active (IMPACT) centers that
      represent 90% of pediatric tertiary care beds in Canada conducted active
      surveillance for varicella-related hospitalizations and complications from 1999
      onward, after varicella vaccine was authorized. Publicly funded routine
      immunization programs at 12 or 15 months of age were introduced by 5 provinces
      and territories (prov/terr) in 2000 to 2002 (earlier programs, EP) and by 8
      prov/terr in 2004 to 2007 (later programs, LP). OBJECTIVE: To determine whether
      the number of varicella-related hospitalized cases had declined by 2008 at 12
      IMPACT centers after the sequential introduction of publicly funded varicella
      immunization programs in Canada. METHODS: Varicella-related hospitalizations from
      2000 to 2008 in the prov/terr with EP were under surveillance by 3 IMPACT centers
      (Halifax, Edmonton, Calgary), whereas the prov/terr with LP were under
      surveillance by the remaining 9 centers. The age, gender, underlying health
      status, varicella complications, and length of stay in hospital and the pediatric
      intensive care unit were documented. Breakthrough cases were identified and their
      clinical characteristics described. RESULTS: Between 2000 and 2008, the number of
      varicella-related hospitalized cases in IMPACT centers declined relatively sooner
      in prov/terr with EP (by 2002 to 2003), as compared to those with LP (only by
      2007 to 2008). In 2008, varicella-related hospitalized cases declined by 88% in
      the EP centers, and by 81% in the LP centers. In all IMPACT centers, the greatest
      decline occurred in the 1-4 years age group (90% decline), with smaller declines
      in both <1 year and 5-9 years age groups (78% and 76% decline, respectively).
      Breakthrough disease accounted for 39 (2%) cases, with the proportion due to
      breakthrough increasing from 0.9% in 2000 to 2001, to 2% in 2003 to 2004 and 9.5%
      in 2007 to 2008. The majority (72%) of breakthrough cases were in
      immunocompromised children. CONCLUSIONS: Publicly funded varicella vaccination
      programs have led to a significant decline in varicella-related hospitalizations
      in Canadian children, as a result of direct effects of the program beginning
      within 1 to 2 years after the start, as well as probable indirect protection of
      children outside the vaccinated cohort.

PMID- 22647897
TI  - Foster care as a viable alternative to institutional care in the Middle East:
      community acceptance and stigma across type of placement in Jordan.
AB  - OBJECTIVE: Utilizing an experimental vignette design, this study assessed
      attitudes in the Hashemite Kingdom of Jordan toward the implementation of foster
      care as an alternative to institutions for children in need of care and
      protection. METHODS: A sample of 111 adults were surveyed in Amman and presented
      with a vignette describing a 14-year-old boy who came into the care of the
      Ministry of Social Development when he was a baby after being placed by the
      grandfather because of shame surrounding the mother being unwed. The vignettes
      systematically varied as to whether the child was described as raised in an
      orphanage, with a relative in a kinship foster placement, or with a nonkin foster
      family. Participants were then asked a series of questions about their acceptance
      of the child, stigma that the community might attach to the child, and potential
      outcomes for the child. RESULTS: We found no differences across the acceptance
      and stigma questions between the kinship and non-kin foster conditions. The 2
      foster care options were at least as acceptable as current institutional models
      across all domains, and participants were more likely to accept the child going
      to school with or being friends with their child if they were in foster care
      rather than an institution. CONCLUSIONS: These results represent the first
      evidence of public acceptance of foster care as a model of care in Jordan and may
      inform the process of local stakeholders implementing alternatives to
      institutional care on a meaningful and sustainable scale in the Kingdom and
      regionally.

PMID- 22647899
TI  - Ecological momentary assessment in alcohol, tobacco, cannabis and opiate
      dependence: a comparison of feasibility and validity.
AB  - BACKGROUND: Despite growing use of computerized ambulatory monitoring in
      substance dependence research, little is known about the comparative feasibility
      and validity of these novel methods by substance type. This study compares the
      feasibility and validity of computerized ambulatory monitoring in outpatients
      seeking treatment for alcohol, tobacco, cannabis or opiate dependence. METHODS: A
      total of 109 participants were recruited from an outpatient treatment center and
      completed standard clinical instruments followed by 2 weeks of computerized
      ambulatory monitoring of daily life experiences and substance use. RESULTS:
      Individuals with cannabis dependence had the lowest rates of study acceptance
      (31%) as well as compliance with the repeated electronic interviews (79.9%),
      while those with tobacco dependence had the highest rates (62% and 91.0%,
      respectively). Concurrent validity was found between scores from standard
      clinical instruments and similar constructs assessed in daily life, with no
      difference by substance group. While no fatigue effects were detected, change in
      some variables was observed as a function of time in the study. CONCLUSIONS:
      Computerized ambulatory protocols are feasible and provide valid data in
      individuals with diverse forms of dependence, but compliance to repeated sampling
      methodology may vary by substance type.

PMID- 22647900
TI  - Prior methamphetamine self-administration attenuates serotonergic deficits
      induced by subsequent high-dose methamphetamine administrations.
AB  - BACKGROUND: Pre-clinical studies indicate that high-dose, non-contingent
      methamphetamine (METH) administration both rapidly and persistently decreases
      serotonergic neuronal function. Despite research indicating the hippocampus plays
      an important role in METH abuse and is affected by METH use, effects of METH self
      administration on hippocampal serotonergic neurons are not well understood, and
      were thus an important focus of the current study. Because humans often
      administer METH in a binge-like pattern, effects of prior METH self
      administration on a subsequent "binge-like" METH treatment were also examined.
      METHODS: Rats were treated as described above, and sacrificed 1 or 8d after self
      administration or 1h or 7d after the final binge METH or saline exposure.
      Hippocampal serotonin (5-hydroxytryptamine; 5HT) content and transporter (SERT)
      function were assessed. RESULTS: METH self-administration per se had no
      persistent effect on hippocampal 5HT content or SERT function. However, this
      treatment attenuated the persistent, but not acute, hippocampal serotonergic
      deficits caused by a subsequent repeated, high-dose, non-continent METH treatment
      administered 1 d the last self-administration session. No attenuation in
      persistent deficits were seen when the high-dose administration of METH occurred
      15d after the last self-administration session. CONCLUSIONS: The present findings
      demonstrate that METH self-administration alters serotonergic neurons so as to
      engender "tolerance" to the persistent serotonergic deficits caused by a
      subsequent METH exposure. However, this "tolerance" does not persist. These data
      provide a foundation to investigate complex questions including how the response
      of serotonergic neurons to METH may contribute to contingent-related disorders
      such as dependence and relapse.

PMID- 22647901
TI  - Investigation of bacterial community in activated sludge with an anaerobic side
      stream reactor (ASSR) to decrease the generation of excess sludge.
AB  - The goal of this study was to investigate the bacterial community in activated
      sludge with an anaerobic side-stream reactor (ASSR), a process permitting
      significant decrease in sludge production during wastewater treatment. The study
      operated five activated sludge systems with different sludge treatment schemes
      serving as various controls for the activated sludge with ASSR. Bacterial
      communities were analyzed by denaturing gradient gel electrophoresis (DGGE),
      sequencing and construction of phylogenetic relationships of the identified
      bacteria. The DGGE data showed that activated sludge incorporating ASSR contained
      higher diversity of bacteria, resulting from long solids retention time and
      recirculation of sludge under aerobic and anaerobic conditions. The similarity of
      DGGE profiles between ASSR and separate anaerobic digester (control) was high
      indicating that ASSR is primarily related to conventional anaerobic digesters.
      Nevertheless, there was also unique bacteria community appearing in ASSR.
      Interestingly, sludge in the main system and in ASSR showed considerably
      different bacterial composition indicating that ASSR allowed enriching its own
      bacterial community different than that from the aeration basin, although two
      reactors were connected via sludge recirculation. In activated sludge with ASSR,
      sequences represented by predominant DGGE bands were affiliated with
      Proteobacteria. The remaining groups were composed of Spirochaetes,
      Clostridiales, Chloroflexi, and Actinobacteria. Their putative role in the
      activated sludge with ASSR is also discussed in this study.

PMID- 22647902
TI  - Sensitivity analysis of some critical factors affecting simulated intrusion
      volumes during a low pressure transient event in a full-scale water distribution
      system.
AB  - Intrusion events caused by transient low pressures may result in the
      contamination of a water distribution system (DS). This work aims at estimating
      the range of potential intrusion volumes that could result from a real downsurge
      event caused by a momentary pump shutdown. A model calibrated with transient low
      pressure recordings was used to simulate total intrusion volumes through leakage
      orifices and submerged air vacuum valves (AVVs). Four critical factors
      influencing intrusion volumes were varied: the external head of (untreated) water
      on leakage orifices, the external head of (untreated) water on submerged air
      vacuum valves, the leakage rate, and the diameter of AVVs' outlet orifice
      (represented by a multiplicative factor). Leakage orifices' head and AVVs'
      orifice head levels were assessed through fieldwork. Two sets of runs were
      generated as part of two statistically designed experiments. A first set of 81
      runs was based on a complete factorial design in which each factor was varied
      over 3 levels. A second set of 40 runs was based on a latin hypercube design,
      better suited for experimental runs on a computer model. The simulations were
      conducted using commercially available transient analysis software. Responses,
      measured by total intrusion volumes, ranged from 10 to 366 L. A second degree
      polynomial was used to analyze the total intrusion volumes. Sensitivity analyses
      of both designs revealed that the relationship between the total intrusion volume
      and the four contributing factors is not monotonic, with the AVVs' orifice head
      being the most influential factor. When intrusion through both pathways occurs
      concurrently, interactions between the intrusion flows through leakage orifices
      and submerged AVVs influence intrusion volumes. When only intrusion through
      leakage orifices is considered, the total intrusion volume is more largely
      influenced by the leakage rate than by the leakage orifices' head. The latter
      mainly impacts the extent of the area affected by intrusion.

PMID- 22647903
TI  - Proteolytic processing of the protein tyrosine phosphatase alpha extracellular
      domain is mediated by ADAM17/TACE.
AB  - The receptor protein tyrosine phosphatase alpha (PTPalpha) is involved in the
      regulation of tyrosine kinases like the Src kinase and the insulin receptor. As
      with other PTPs, its function is determined by alternative splicing,
      dimerisation, phosphorylation and proteolytical processing. PTPalpha is cleaved
      by calpain in its intracellular domain, which decreases its potential to
      dephosphorylate Src kinase. Here, we demonstrate that PTPalpha is also processed
      in the extracellular domain. Extracellular processing was exclusively found for a
      splice variant containing an extra nine amino acid insert three residues amino
      terminal from the transmembrane domain. Processing was sensitive to the
      metalloprotease-inhibitor Batimastat, and CHO-M2 cells lacking a disintegrin and
      metalloproteinase 17 (ADAM17; tumor-necrosis-factor alpha converting enzyme)
      activity were not able to cleave PTPalpha. After transient overexpression of
      ADAM17 and PTPalpha in these cells, processing was restored, proving that ADAM17
      is involved in this process. Further characterization of the consequences of
      processing revealed that dephosphorylation of the insulin receptor or activation
      of Src was not affected but focus formation was reduced. We conclude that
      extracellular proteolytic processing is a novel mechanism for PTPalpha
      regulation.

PMID- 22647904
TI  - The isoform B of the Dictyostelium long-chain fatty-acyl-coenzyme A synthetase is
      initially inserted into the ER and subsequently provides peroxisomes with an
      activity important for efficient phagocytosis.
AB  - Long-chain fatty-acyl-coenzyme A synthetases activate fatty acids for anabolic or
      catabolic metabolism. They often localize to more than one organelle within
      eukaryotic cells. Dictyostelium contains two of these proteins, FcsA and FcsB
      with the latter being targeted to the membrane of the endoplasmic reticulum by
      virtue of an N-terminal signal sequence and from there appears to move on to
      peroxisomes. Deletion of this signal favors the peripheral association of the
      protein with the mitochondrial surface instead. A strain lacking the activity of
      the FcsB enzyme was constructed by homologous recombination. It has a severe
      deficiency in the phagocytic uptake of particles, which can be partially
      alleviated by a peroxisomally targeted, soluble FcsA enzyme. It is, however, not
      rescued by expressing FcsA in the cytoplasm or targeting it to the ER, indicating
      that peroxisomal beta-oxidation is important for phagocytosis. In a fcsA(-)/B(-)
      double mutant phagocytosis efficiency is similar to fcsB(-) cells. However,
      unlike the single mutants, the fcsA(-)/B(-) strain is delayed in morphogenesis,
      but forms viable spores, albeit within a small fruiting body. This developmental
      defect is also seen in other mutants affecting peroxisomal enzymes involved in
      beta-oxidation and the glyoxylate cycle.

PMID- 22647905
TI  - Chronic radiation exposure:  small-dose effects.

PMID- 22647906
TI  - Ischemic heart disease in nuclear workers first employed at the Mayak PA in 1948
      1972.
AB  - Following an earlier study of incidence and mortality of ischemic heart disease
      (IHD) published in 2010, a second analysis has been conducted based on an
      extended cohort and five additional years of follow-up. The cohort includes
      18,763 workers, of whom 25% were females, first employed at the Mayak PA in 1948
      1972 and followed up to the end of 2005. Some of these workers were exposed to
      external gamma rays only, and others were exposed to a mixture of external gamma
      rays and internal alpha-particle radiation. A total of 6,134 cases and 2,629
      deaths from IHD were identified in the study cohort. A statistically significant
      increasing trend was found with total external gamma-ray dose in IHD incidence
      (ERR/Gy 0.099; 95% CI: 0.045-0.153) after adjusting for non-radiation factors.
      This value reduced slightly when adjusting for internal liver dose. There was no
      statistically significant increase trend for internal liver dose in IHD
      incidence. These findings were consistent with an earlier study. New findings in
      IHD incidence revealed a statistically significant decrease in IHD incidence
      among workers exposed to external gamma-rays doses of 0.2-0.5 Gy in relation to
      the external doses below 0.2 Gy. This decreased risk is heavily influenced by
      female workers. This finding has never been reported in other studies, and the
      results should be treated with caution. The findings for IHD mortality are
      similar to those results in the earlier analysis; there was no statistically
      significant trend with external gamma-ray dose or for internal liver dose after
      adjustment for external dose. The risk estimates obtained from these analyses of
      IHD incidence and mortality in relation to external gamma-rays in the cohort of
      Mayak workers are generally compatible with those from other large occupational
      radiation worker studies and the Japanese atomic bomb survivors.

PMID- 22647907
TI  - The risk of acute myocardial infarction and arterial hypertension in a cohort of
      male employees of a Siberian Group of Chemical Enterprises exposed to long-term
      irradiation.
AB  - During the period from 1998 to 2007, a prospective cohort study of acute
      myocardial infarction morbidity cases as well as a "case-control" study of
      arterial hypertension was carried out. The risk of acute myocardial infarction
      was assessed as well as arterial hypertension; the dose-response relationship and
      the role of radiation in the mechanism of acute myocardial infarction as well as
      arterial hypertension development were studied. As a result of this study, a
      statistically significant increased risk of acute myocardial infarction among the
      male staff at the Siberian Group of Chemical Enterprises [standardized relative
      risk = 1.16 (1.04; 1.29)] exposed to external irradiation in comparison with
      employees unexposed to ionizing radiation was observed. A significant increase in
      the risk of acute myocardial infarction was observed at external radiation dose
      accumulation of more than 300 mSv [standardized relative risk = 1.46 (1.09;
      1.91)]. The increase in arterial hypertension risk has been established among the
      analyzed group of employees exposed to long-term irradiation in the absence of
      the linear dependence of risk, based on cumulative dose of external gamma
      irradiation [risk due to external radiation dose in the range of 7.3-21.3 mSv =
      1.6 (0.96; 2.51) and in the range of external radiation dose 21.4-68.5 mSv = 1.7
      (1.04; 2.67) for 68.6-864 mSv = 1.6 (1.01; 2.57)]. This led to the conclusion
      that radiation can act also as a factor that might potentiate the negative
      effects of the "traditional" risk factors in the pathogenesis of acute myocardial
      infarction and hypertension.

PMID- 22647908
TI  - Thyroid cancer incidence due to technogenic exposure in childhood.
AB  - Thyroid cancer incidence was studied in the cohort of residents of Ozyorsk and
      Kyshtym, the nearest upwind cities to the Mayak Production Association (Mayak
      PA), Russia's first plutonium production facility, which has been in operation
      since 1948. Radioactive contamination of areas around the Mayak PA were from
      unmonitored releases of inert gases produced by industrial reactors and also from
      the release of uranium fission products from a radiochemical plant stack where
      irradiated uranium blocks were refined. Iodine-131 (131I) was the main
      contributor to the technogenic dose from atmospheric releases. Routine monitoring
      of gaseous releases began in the mid-1960s, when a gas purification system was
      perfected. Children were a critical group due to their higher radiosensitivity
      and specific diet (dairy products and vegetables). Both cities maintain
      Registries containing over 100,000 individuals born from 1934-2006. Among this
      group, more than 100 cases of thyroid cancer were registered during 1948-2009.
      The relative risk of thyroid cancer incidence is 1.5 times higher than in the
      Chelyabinsk.

PMID- 22647909
TI  - Quantitative assessment of regulatory proteins in blood as markers of radiation
      effects in the late period after occupational exposure.
AB  - The objective of this research was quantitative assessment of serum and membrane
      regulatory proteins in blood from nuclear workers as markers of radiation-induced
      alterations in immune homeostasis in the late period after protracted exposure of
      nuclear workers with different doses. The effector and regulatory lymphocytes
      were measured using a flow cytofluorometer in workers from the main facilities of
      the Mayak PA (aged ~60 y up to 80 y) in the late period after combined exposure
      to external gamma-rays and internal alpha-radiation from incorporated 239Pu. The
      control group included non-occupationally exposed members of the Ozyorsk
      population matched by gender and age to the group of Mayak workers. Thirty serum
      proteins involved in regulation of immune homeostasis, such as growth factors,
      multifunctional interleukins, pro- and anti-inflammatory cytokines, and their
      receptors, were measured using ELISA in blood serum specimens from the
      Radiobiology Human Tissue Repository. The dosimetry estimates were obtained using
      Doses-2005. The correlation analysis revealed a statistically significant direct
      relationship of T-killers and plutonium body burden and a decreasing level of T
      helpers with accumulated external dose in exposed individuals. There were
      differences in expression of membrane markers in young regulatory cells (double
      null T-lymphocytes, NKT-lymphocytes, regulatory T-cells, and an increase of
      activated forms of T-lymphocytes), which indicated an active role of regulatory
      cells in maintaining immune homeostasis in terms of protracted exposure. The
      assessment of regulatory proteins in blood indicated that growth factors (EGF,
      TGF-beta1, PDGF), multifunctional interleukins (IL-17A, IL-18), and pro
      inflammatory cytokines (IL-1beta and INF-gamma) could be potential markers of
      radiation-induced alterations in protein status. An imbalance of pro- and
      antiinflammatory proteins in blood and variations of protein profiles at the
      lower exposure levels (gamma-ray dose <1 Gy, plutonium body burden <0.74 kBq) in
      the late period after protracted exposure were less pronounced than at the higher
      exposure levels, which was probably explained by compensatory-adaptive responses
      in the late period among senile individuals with polypathology.

PMID- 22647910
TI  - Correlations between DNA polymorphism and frequencies of gamma-radiation induced
      and spontaneous cytogenetic damage.
AB  - With the aim of developing genetic tests for elevated and reduced radiation
      sensitivity, the authors studied the correlations between various genotypes and
      frequencies of spontaneous and radiation-induced chromosome aberrations in human
      lymphocytes. Cytogenetic analysis and genotyping (19 sites of detoxification and
      DNA repair genes) were carried out for a group of cleanup workers of the
      Chernobyl nuclear power plant accident (83 people) and for a uniform control
      group of volunteers (97 people). In both cases, the frequencies of chromosome
      type aberrations were higher in carriers of minor alleles of gene XPD [sites
      T2251G (Lys751Gln) and G862A (Asp312Asn)] and the "positive" genotypes
      GSTM1/GSTT1. The polymorphism of these genes did not affect the frequency of
      aberrations induced by gamma radiation in the control group (1 Gy in vitro),
      which was associated with genotypes by loci OGG1, XRCC1, and CYP1A1. Thus, in the
      control group, spontaneous and in vitro induced cytogenetic effects are
      associated with different groups of polymorphic genes. In the cleanup workers
      group (irradiated in vivo), the elevated frequency of aberrations was observed in
      the carriers of those genotypes that typically have a higher level of spontaneous
      (but not in vitro induced) cytogenetic damage in the control. The genotype "minor
      XPD + insertion GST," having an estimated incidence of 64% in central Russia, was
      characterized and found to be strongly associated with an elevated frequency of
      chromosome type aberrations following irradiation in vivo (OR = 6.9; p = 0.008).

PMID- 22647911
TI  - Main dependencies in reduction of radiation exposure to the population of the
      Southern Urals.
AB  - Dynamics of soil contamination, food chain, and radiation doses to population at
      the East-Urals Radioactive Trace (EURT) and the Karachay Radioactive Trace (KRT)
      are reviewed. Gamma spectrometric analysis of samples was performed according to
      standard methodology; 90Sr was determined by the extraction method. Over 80% of
      radionuclides in soil are contained in the upper 20-cm layer. Biologically
      available forms of Sr and insoluble forms of 137Cs are predominant. The main
      reasons for reduction in milk contamination are radioactive decay and
      sequestration of radionuclides in soil. Current annual intake of radionuclides
      with food: EURT--310 Bq (90Sr), KRT--324 Bq (90Sr) and 732 Bq (137Cs).

PMID- 22647912
TI  - Characteristics of phytoplankton in Lake Karachay, a storage reservoir of medium
      level radioactive waste.
AB  - The status of the phytoplankton community in Lake Karachay, a storage reservoir
      of liquid medium-level radioactive waste from the Mayak Production Association,
      Chelyabinsk Region, Russia, is reviewed. In 2010, the concentration of Sr in
      water of this reservoir was found to be 6.5 * 10(6) Bq L, the concentration of
      137Cs was 1.6 * 10(7) Bq L, and total alpha activity amounted to 3.0 * 10(3) Bq
      L. An increased level of nitrates was observed in the reservoir-4.4 g L. It has
      been demonstrated that in this reservoir under the conditions of the maximum
      contamination levels known for aquatic ecosystems in the entire biosphere, a
      phytoplankton community exists that has a pronounced decline in species
      diversity, almost to the extent of a monoculture of widely-spread thread
      eurytopic cyanobacteria Geitlerinema amphibium.

PMID- 22647913
TI  - Adaptive response of blood lymphocytes as a marker of hemopoiesis status in
      exposed persons.
AB  - After the onset of a long-term low dose rate radiation exposure (55-60 y later)
      of the Techa riverside residents within a range of individual red bone marrow
      (RBM) doses from 0.01 to 1.79 Gy, it was established that there was an obvious
      association between the type of reaction manifested by peripheral blood
      lymphocytes to small dose irradiation in vitro (adaptive potential) and the RBM
      cell composition (during the period of the major exposure), as well as the
      peripheral blood cell composition (at a late time period coincident with the
      studies of induced radioresistance). The nature of these dependencies observed in
      chronically exposed individuals differs from that revealed in the controls. Based
      on the results of the study, it can be suggested that the capacity for adaptive
      response shown by peripheral blood lymphocytes donated by exposed persons at late
      time after exposure can be regarded as a biological marker of the functional
      state of the hemopoietic stem cell pool.

PMID- 22647914
TI  - Qualitative assessment of sources and general dependencies in the behavior of
      anthropogenic radionuclides in the Techa River.
AB  - Research on radioactive contamination of the environment involves the important
      task of assessing the contribution from different sources of contamination. If
      there are two or more sources of contamination with similar radionuclide
      composition, assessment of the contribution from each source can be challenging.
      Such a problem exists, for instance, in the assessment of anthropogenic sources
      of radioactive contamination of water in the Techa River. At the present time,
      the main contaminating radionuclides for the Techa River are 90Sr, 137Cs, and 3H.
      In 2009-2010, the content of radionuclides in the water of the river was 90Sr-3.8
      32.9 Bq L, 137Cs-0.02-2.43 Bq L, and 3H-31.0-263.2 Bq L. This work gives a
      qualitative assessment of the role of different contamination sources in the
      formation of volumetric activity of Sr in the water of the Techa River. Also, the
      behavior of anthropogenic radionuclides in the open fluvial river system is
      reviewed.

PMID- 22647915
TI  - Research into the factors affecting the uptake of 90Sr and 137Cs by plants from
      radioactively contaminated soils of the southern Urals.
AB  - The objective of this work was to study the factors affecting the intake of 90Sr
      and 137Cs by plants from soils exposed to radioactive contamination resulting
      from operations of the Mayak Industrial Association. Specific activities of 90Sr
      and 137Cs in the samples were determined by the radiochemical method. The most
      severe contamination by 90Sr and 137Cs of natural soils was found in forest soil
      cover and in the 0-5 cm soil layer. The contamination density of the area is
      mainly determined by activity in the soil layer 0-20 cm that contains 3-97% of
      90Sr and 60-92% of 137Cs. Portions of radionuclides contained in soil (89-96% of
      90Sr and 18-73% of 137Cs) can be converted into cationic use. An insignificant
      share of water-soluble radionuclides goes from soil to agricultural produce.

PMID- 22647916
TI  - Apoptosis of peripheral blood lymphocytes and mutations in the gene of the T-cell
      receptor in survivors of chronic radiation exposure.
AB  - This research has been conducted to study the activity of apoptosis of peripheral
      blood lymphocytes (PBLs) and the frequency of CD3-/CD4+ PBLs in people who have
      suffered chronic low-intensity radiation exposure. An increase in the frequency
      of apoptotic cells (TUNEL) is demonstrated in the group of exposed individuals
      relative to the control group. The frequency of mutations in the gene of the T
      cell receptor in the exposed individuals is also elevated. Analyses of the mean
      values of apoptosis and CD3-CD4+ PBLs in different dose subgroups have found an
      increase in the proportion of cells with mutant T-cell receptors against the
      background of a decrease in the frequency of apoptotic cells in the range of low
      and medium radiation doses.

PMID- 22647917
TI  - Status of ecosystems in radioactive waste reservoirs of the Mayak Production
      Association in 2009.
AB  - Liquid radioactive waste from the Mayak Production Association (Chelyabinsk
      Region, Russia) is contained in industrial reservoirs (R-11, R-10, R-4, R-17, and
      R-9) that have different levels of radioactive contamination, increased from R-11
      to R-17. A study of the ecosystems in these reservoirs was performed in 2009 to
      determine if there was any association with the level of contamination. No
      significant change in the status of biota was found in the reservoir with the
      lowest radionuclide concentrations (R-11) in comparison to other reservoirs in
      the region with a similar geography that are unaffected by radioactive
      contamination. In reservoir R-10, changes in the zoobenthos indices were
      registered. In reservoir R-4, changes in the zoobenthos and zooplankton
      communities were registered. In reservoir R-17, there was no ichthyofauna, but
      strong changes in the phytoplankton, zooplankton, and zoobenthos communities were
      registered. In reservoir R-9, under the conditions of the heaviest radioactive
      contamination of water ecosystems in the biosphere, there was no ichthyofauna,
      and phytoplankton and zooplankton consisted of almost a monoculture of
      cyanobacteriae and rotifers.

PMID- 22647918
TI  - Utility of digital radiography for the screening of pneumoconiosis as compared to
      analog radiography:  radiation dose, image quality, and pneumoconiosis
      classification.
AB  - The purpose of this study was to compare digital radiography (DR) and analog
      radiography (AR) for the screening of pneumoconiosis with respect to radiation
      dose, image quality, and pneumoconiosis classification. DR was performed on 50
      subjects who were enrolled for an examination of pneumoconiosis (Digital
      DiagnostTM, Philips, Netherlands), and AR (MXO-15B, Toshiba, Japan) was performed
      the same day after the study was approved by the Institutional Review Board and
      written informed consent was obtained from all subjects. Entrance surface doses
      (ESDs) of DR and AR were measured using a glass dosimeter attached to a Rando
      human phantom (Alderson Co., U.S.) under exposure conditions commonly used in
      clinical practice in Korea. Visibilities on all images were evaluated using a 5
      point scale by four chest radiologists using a modified form of the European
      Chest Guidelines (EUR 16260). All the images were classified using the ILO's
      guidelines by referencing standard analog radiographs. ESDs of DR were
      significantly lower than those of AR (0.15 mGy vs. 0.21 mGy, p < 0.05). All
      anatomic structures were significantly more visible by DR images (p < 0.0001),
      especially the left main bronchus, ribs, and thoracic spine. Body mass index did
      not correlate with anatomic structure visibility by DR (r = -0.029, p = 0.842) or
      AR images (r = -0.076, p = 0.602). Overall intra- and inter-reader agreements for
      DR images were significantly higher than for AR images. DR offers improved image
      quality with a significant reduction of up to 23.6% in radiation dose and more
      accurate pneumoconiosis classification than AR.

PMID- 22647919
TI  - Maximum likelihood analysis of bioassay data from long-term follow-up of two
      refractory PuO2 inhalation cases.
AB  - The U.S. Transuranium and Uranium Registries' tissue donors 0202 and 0407 are the
      two most highly exposed of the 18 registrants who were involved in the 1965
      plutonium fire accident at a defense nuclear facility. Material released during
      the fire was well characterized as "high fired" refractory plutonium dioxide with
      0.32-MUm mass median diameter. The extensive bioassay data from long-term follow
      up of these two cases were used to evaluate the applicability of the Human
      Respiratory Tract Model presented by International Commission on Radiological
      Protection in Publication 66 and its revision proposed by Gregoratto et al. in
      order to account for the observed long-term retention of insoluble material in
      the lungs. The maximum likelihood method was used to calculate the point
      estimates of intake and tissue doses and to examine the effect of different lung
      clearance, blood absorption, and systemic models on the goodness-of-fit and
      estimated dose values. With appropriate adjustments, Gregoratto et al. particle
      transport model coupled with the customized blood absorption parameters yielded a
      credible fit to the bioassay data for both cases and predicted the Case 0202
      liver and skeletal activities measured postmortem. PuO2 particles produced by the
      plutonium fire are extremely insoluble. About 1% of this material is absorbed
      from the respiratory tract relatively rapidly, at a rate of about 1 to 2 d (half
      time about 8 to 16 h). The remainder (99%) is absorbed extremely slowly, at a
      rate of about 5 * 10(-6) d (half-time about 400 y). When considering this
      situation, it appears that doses to other body organs are negligible in
      comparison to those to tissues of the respiratory tract. About 96% of the total
      committed weighted dose equivalent is contributed by the lungs. Doses absorbed by
      these workers' lungs were high: 3.2 Gy to AI and 6.5 Gy to LNTH for Case 0202 (18
      y post-intake) and 3.2 Gy to AI and 55.5 Gy to LNTH for Case 0407 (43 y post
      intake). This evaluation supports the Gregoratto et al. proposed revision to the
      ICRP 66 model when considering situations of extremely insoluble particles.

PMID- 22647921
TI  - Submerged RadBall(r) deployments in Hanford Site hot cells containing 137CsCl
      capsules.
AB  - The overall objective of this study was to demonstrate that a new technology,
      known as RadBall(r), could locate submerged radiological hazards. RadBall(r) is a
      novel, passive, radiation detection device that provides a 3-D visualization of
      radiation from areas where measurements have not been previously possible due to
      lack of access or extremely high radiation doses. This technology has been under
      development during recent years, and all of its previous tests have included dry
      deployments. This study involved, for the first time, underwater RadBall(r)
      deployments in hot cells containing 137CsCl capsules at the U.S. Department of
      Energy's Hanford Site. RadBall(r) can be used to characterize a contaminated
      room, hot cell, or glovebox by providing the locations of the radiation sources
      and hazards, identifying the radionuclides present within the cell, and
      determining the radiation sources' strength (e.g., intensities or dose rates).
      These parameters have been previously determined for dry deployments; however,
      only the location of radiation sources and hazards can be determined for an
      underwater RadBall(r) deployment. The results from this study include 3-D images
      representing the location of the radiation sources within the Hanford Site cells.
      Due to RadBall(r)'s unique deployability and non-electrical nature, this
      technology shows significant promise for future characterization of radiation
      hazards prior to and during the decommissioning of contaminated nuclear
      facilities.

PMID- 22647920
TI  - Occupational radiation doses to operators performing fluoroscopically-guided
      procedures.
AB  - In the past 30 y, the numbers and types of fluoroscopically-guided (FG)
      procedures have increased dramatically. The objective of the present study is to
      provide estimated radiation doses to physician specialists, other than
      cardiologists, who perform FG procedures. The authors searched Medline to
      identify English-language journal articles reporting radiation exposures to these
      physicians. They then identified several primarily therapeutic FG procedures that
      met specific criteria: well-defined procedures for which there were at least five
      published reports of estimated radiation doses to the operator, procedures
      performed frequently in current medical practice, and inclusion of physicians
      from multiple medical specialties. These procedures were percutaneous
      nephrolithotomy (PCNL), vertebroplasty, orthopedic extremity nailing for
      treatment of fractures, biliary tract procedures, transjugular intrahepatic
      portosystemic shunt creation (TIPS), head/neck endovascular therapeutic
      procedures, and endoscopic retrograde cholangiopancreatography (ERCP). Radiation
      doses and other associated data were abstracted, and effective dose to operators
      was estimated. Operators received estimated doses per patient procedure
      equivalent to doses received by interventional cardiologists. The estimated
      effective dose per case ranged from 1.7-56 MUSv for PCNL, 0.1-101 MUSv for
      vertebroplasty, 2.5-88 MUSv for orthopedic extremity nailing, 2.0-46 MUSv for
      biliary tract procedures, 2.5-74 MUSv for TIPS, 1.8-53 MUSv for head/neck
      endovascular therapeutic procedures, and 0.2-49 MUSv for ERCP. Overall, mean
      operator radiation dose per case measured over personal protective devices at
      different anatomic sites on the head and body ranged from 19-800 (median = 113)
      MUSv at eye level, 6-1,180 (median = 75) MUSv at the neck, and 2-1,600 (median =
      302) MUSv at the trunk. Operators' hands often received greater doses than the
      eyes, neck, or trunk. Large variations in operator doses suggest that optimizing
      procedure protocols and proper use of protective devices and shields might reduce
      occupational radiation dose substantially.

PMID- 22647925
TI  - Conventional versus 3-dimensional miniplate in management of mandibular fracture:
      a prospective randomized study.
AB  - OBJECTIVE: The aim of this study was to compare conventional miniplate (Champy's)
      and 3-dimensional miniplate fixation in the management of mandibular fracture.
      STUDY DESIGN: Prospective study. SETTING: The study was carried out in the
      Department of Oral and Maxillofacial Surgery, Govt. Dental College, Pt. B.D.
      Sharma University of Health Sciences, Rohtak, India. SUBJECTS AND METHODS: A
      prospective randomized clinical trial was carried out in 50 patients. Patients
      were randomly assigned to receive a 2.0-mm 3-dimensional miniplate (group A) or a
      2.0-mm conventional miniplate (group B). All patients were followed up for 12
      weeks postoperatively. Complications were analyzed according to the type of plate
      used and the site of fracture. RESULTS: Twenty-eight fracture sites were treated
      with the 3-dimensional miniplate and 28 with the conventional miniplate. Five
      complications occurred, representing 8.9% of the total. Two complications
      occurred in group A and 3 in group B, with complication rates equaling 7.14% and
      10.71%, respectively. When comparing the overall complication rates according to
      plates used, the chi(2) test showed no statistically significant difference
      between the 2 groups (P > .05). CONCLUSION: No major difference in terms of
      treatment outcome is observed in both systems, and both are equally effective in
      managing mandibular fracture.

PMID- 22647926
TI  - Gift-giving in the medical student--patient relationship.
AB  - There is paucity in the published literature that provides any ethical guidance
      guiding gift-giving within the student--patient relationship. This is perhaps
      because the dynamics of the medical student--patient relationship have not yet
      been explored as extensively as the doctor--patient relationship. More
      importantly, however, gift--giving in the doctor-patient relationship has
      traditionally been from the patient to the doctor and not vice versa. This
      article examines the literature published in this vicinity reflecting on an
      encounter with a patient.

PMID- 22647927
TI  - Combined bottom-up and top-down mass spectrometry analyses of the pattern of post
      translational modifications of Drosophila melanogaster linker histone H1.
AB  - Linker histone H1 is a major chromatin component that binds internucleosomal DNA
      and mediates the folding of nucleosomes into a higher-order structure, namely the
      30-nm chromatin fiber. Multiple post-translational modifications (PTMs) of core
      histones H2A, H2B, H3 and H4 have been identified and their important
      contribution to the regulation of chromatin structure and function is firmly
      established. In contrast, little is known about histone H1 modifications and
      their function. Here we address this question in Drosophila melanogaster, which,
      in contrast to most eukaryotic species, contains a single histone H1 variant,
      dH1. For this purpose, we combined bottom-up and top-down mass-spectrometry
      strategies. Our results indicated that dH1 is extensively modified by
      phosphorylation, methylation, acetylation and ubiquitination, with most PTMs
      falling in the N-terminal domain. Interestingly, several dH1 N-terminal
      modifications have also been reported in specific human and/or mouse H1 variants,
      suggesting that they have conserved functions. In this regard, we also provide
      evidence for the contribution of one of such conserved PTMs, dimethylation of
      K27, to heterochromatin organization during mitosis. Furthermore, our results
      also identified multiple dH1 isoforms carrying several phosphorylations and/or
      methylations, illustrating the high structural heterogeneity of dH1. In
      particular, we identified several non-CDK sites at the N-terminal domain that
      appear to be hierarchically phosphorylated. This study provides the most
      comprehensive PTM characterization of any histone H1 variant to date.

PMID- 22647928
TI  - Twelve automated thresholding methods for segmentation of PET images: a phantom
      study.
AB  - Tumor volume delineation over positron emission tomography (PET) images is of
      great interest for proper diagnosis and therapy planning. However, standard
      segmentation techniques (manual or semi-automated) are operator dependent and
      time consuming while fully automated procedures are cumbersome or require complex
      mathematical development. The aim of this study was to segment PET images in a
      fully automated way by implementing a set of 12 automated thresholding
      algorithms, classical in the fields of optical character recognition, tissue
      engineering or non-destructive testing images in high-tech structures. Automated
      thresholding algorithms select a specific threshold for each image without any a
      priori spatial information of the segmented object or any special calibration of
      the tomograph, as opposed to usual thresholding methods for PET. Spherical (18)F
      filled objects of different volumes were acquired on clinical PET/CT and on a
      small animal PET scanner, with three different signal-to-background ratios.
      Images were segmented with 12 automatic thresholding algorithms and results were
      compared with the standard segmentation reference, a threshold at 42% of the
      maximum uptake. Ridler and Ramesh thresholding algorithms based on clustering and
      histogram-shape information, respectively, provided better results that the
      classical 42%-based threshold (p < 0.05). We have herein demonstrated that fully
      automated thresholding algorithms can provide better results than classical PET
      segmentation tools.

PMID- 22647929
TI  - Triploid plover female provides support for a role of the W chromosome in avian
      sex determination.
AB  - Two models, Z Dosage and Dominant W, have been proposed to explain sex
      determination in birds, in which males are characterized by the presence of two Z
      chromosomes, and females are hemizygous with a Z and a W chromosome. According to
      the Z Dosage model, high dosage of a Z-linked gene triggers male development,
      whereas the Dominant W model postulates that a still unknown W-linked gene
      triggers female development. Using 33 polymorphic microsatellite markers, we
      describe a female triploid Kentish plover Charadrius alexandrinus identified by
      characteristic triallelic genotypes at 14 autosomal markers that produced viable
      diploid offspring. Chromatogram analysis showed that the sex chromosome
      composition of this female was ZZW. Together with two previously described ZZW
      female birds, our results suggest a prominent role for a female determining gene
      on the W chromosome. These results imply that avian sex determination is more
      dynamic and complex than currently envisioned.

PMID- 22647930
TI  - Biologically meaningful coverage indicators for eliminating malaria transmission.
AB  - Mosquitoes, which evade contact with long-lasting insecticidal nets and indoor
      residual sprays, by feeding outdoors or upon animals, are primary malaria vectors
      in many tropical countries. They can also dominate residual transmission where
      high coverage of these front-line vector control measures is achieved.
      Complementary strategies, which extend insecticide coverage beyond houses and
      humans, are required to eliminate malaria transmission in most settings. The
      overwhelming diversity of the world's malaria transmission systems and optimal
      strategies for controlling them can be simply conceptualized and mapped across
      two-dimensional scenario space defined by the proportion of blood meals that
      vectors obtain from humans and the proportion of human exposure to them which
      occurs indoors.

PMID- 22647931
TI  - Hot or not? Thermal reactions to social contact.
AB  - Previous studies using thermal imaging have suggested that face and body
      temperature increase during periods of sexual arousal. Additionally, facial skin
      temperature changes are associated with other forms of emotional arousal,
      including fear and stress. This study investigated whether interpersonal social
      contact can elicit facial temperature changes. Study 1: infrared images were
      taken during a standardized interaction with a same- and opposite-sex
      experimenter using skin contact in a number of potentially high-intimate (face
      and chest) and low-intimate (arm and palm) locations. Facial skin temperatures
      significantly increased from baseline during the face and chest contact, and
      these temperature shifts were larger when contact was made by an opposite-sex
      experimenter. Study 2: the topography of facial temperature change was
      investigated in five regions: forehead, periorbital, nose, mouth and cheeks.
      Increased temperature in the periorbital, nose and mouth regions predicted
      overall facial temperature shifts to social contact. Our findings demonstrate
      skin temperature changes are a sensitive index of arousal during interpersonal
      interactions.

PMID- 22647932
TI  - Comparison of patient-reported visual outcome methods to quantify the perceptual
      effects of defocus.
AB  - PURPOSE: Patient-reported subjective responses have become increasingly popular
      in describing contact lens visual performance and discriminating between designs.
      The purpose of the current study is to evaluate the ability of patient-reported
      measures of vision to quantify the perceptual effects of defocus. METHODS: Ten
      young (18-35 years) subjects rated their subjective visual performance
      monocularly on 3 scales following wear of their optimal monocular distance
      correction and nine different blurring lenses (-0.50 to +1.50 in 0.25 D steps) in
      a trial frame. The three scales used were a 0-100 numeric rating scale (NRS), a
      100 mm visual analog scale (VAS), and a 5 point ("Poor", "Fair", "Average",
      "Good", "Excellent") categorical rating scale (CRS). RESULTS: Mixed linear
      modeling results found no significant effects either for eye or trial number, but
      did find a significant effect due to blurring lens power (p<0.0001), with ratings
      decreasing with increasing levels of blur for all scales. Results were not
      significantly different between the NRS and VAS at any level of blur, with limits
      of agreement falling within 22% of the measurement scale. CRS ratings were about
      15 units lower than the other scales on average, with limits of agreement that
      varied with lens power and were roughly 3 times as large. Across scale internal
      consistency was 0.94. CONCLUSIONS: The NRS and VAS yield virtually identical
      rating responses, but both differing slightly, however from the CRS. Each scale
      successfully discriminated levels of blur smaller than 0.25 D with only a single
      measurement.

PMID- 22647934
TI  - Id-1 plays a key role in cell adhesion in neural stem cells through the
      preservation of RAP1 signaling.

PMID- 22647933
TI  - Persistent negative symptoms in first episode patients with schizophrenia:
      results from the European First Episode Schizophrenia Trial.
AB  - Negative symptoms that do not improve following antipsychotic treatment represent
      a challenge for development of effective treatments. Few studies have been
      carried out so far, especially in first-episode schizophrenia patients, to
      clarify prevalence, correlates and impact of persistent negative symptoms (PNS)
      on short- and long-term outcome of the disease. All patients from EUFEST study
      for whom both baseline and 12-month assessments were available were included
      (N=345). PNS were defined as the presence of at least one negative symptom of
      moderate or higher severity, not confounded by depression or parkinsonism, at
      baseline and after 1 year of treatment. Patients with PNS were compared to those
      with at least one negative symptom of moderate or higher severity at the
      baseline, not persisting after 1 year, on demographic, clinical, neurocognitive,
      global functioning and quality of life measures. PNS not confounded by depression
      or parkinsonism were present in 6.7% of the sample. The symptom that more often
      persisted was blunted affect. Patients with PNS differed from those without PNS
      for a longer duration of untreated psychosis (DUP) and a more frequent
      discontinuation of study treatment; they also had a poorer psychopathological
      outcome and a worse global functioning after 1 year of treatment. The presence of
      PNS was associated to poorer improvement of all psychopathological dimensions and
      worse global functioning after 1 year of treatment. The longer DUP in subjects
      with PNS suggests that programs aimed at shortening DUP might reduce the
      prevalence of PNS and improve prognosis of schizophrenia.

PMID- 22647935
TI  - "Importin" signaling roles for import proteins: the function of Drosophila
      importin-7 (DIM-7) in muscle-tendon signaling.
AB  - The formation of a mature myotendinous junction (MTJ) between a muscle and its
      site of attachment is a highly regulated process that involves myofiber
      migration, cell-cell signaling, and culminates with the stable adhesion between
      the adjacent muscle-tendon cells. Improper establishment or maintenance of muscle
      tendon attachment sites results in a decrease in force generation during muscle
      contraction and progressive muscular dystrophies in vertebrate models. Many
      studies have demonstrated the important role of the integrins and integrin
      associated proteins in the formation and maintenance of the MTJ. We recently
      demonstrated that moleskin (msk), the gene that encodes for Drosophila importin-7
      (DIM-7), is required for the proper formation of muscle-tendon adhesion sites in
      the developing embryo. Further studies demonstrated an enrichment of DIM-7 to the
      ends of muscles where the muscles attach to their target tendon cells. Genetic
      analysis supports a model whereby msk is required in the muscle and signals via
      the secreted epidermal growth factor receptor (Egfr) ligand Vein to regulate
      tendon cell maturation. These data demonstrate a novel role for the canonical
      nuclear import protein DIM-7 in establishment of the MTJ.

PMID- 22647936
TI  - Role of the actin-binding protein profilin1 in radial migration and glial cell
      adhesion of granule neurons in the cerebellum.
AB  - Profilins are small G-actin-binding proteins essential for cytoskeletal dynamics.
      Of the four mammalian profilin isoforms, profilin1 shows a broad expression
      pattern, profilin2 is abundant in the brain, and profilin3 and profilin4 are
      restricted to the testis. In vitro studies on cancer and epithelial cell lines
      suggested a role for profilins in cell migration and cell-cell adhesion. Genetic
      studies in mice revealed the importance of profilin1 in neuronal migration, while
      profilin2 has apparently acquired a specific function in synaptic physiology. We
      recently reported a mouse mutant line lacking profilin1 in the brain; animals
      display morphological defects that are typical for impaired neuronal migration.
      We found that during cerebellar development, profilin1 is specifically required
      for radial migration and glial cell adhesion of granule neurons. Profilin1
      mutants showed cerebellar hypoplasia and aberrant organization of cerebellar
      cortex layers, with ectopically arranged granule neurons. In this commentary, we
      briefly introduce the profilin family and summarize the current knowledge on
      profilin activity in cell migration and adhesion. Employing cerebellar granule
      cells as a model, we shed some light on the mechanisms by which profilin1 may
      control radial migration and glial cell adhesion. Finally, a potential
      implication of profilin1 in human developmental neuropathies is discussed.

PMID- 22647937
TI  - The regulation of integrin function by divalent cations.
AB  - Integrins are a family of alpha/beta heterodimeric adhesion metalloprotein
      receptors and their functions are highly dependent on and regulated by different
      divalent cations. Recently advanced studies have revolutionized our perception of
      integrin metal ion-binding sites and their specific functions. Ligand binding to
      integrins is bridged by a divalent cation bound at the MIDAS motif on top of
      either alpha I domain in I domain-containing integrins or beta I domain in alpha
      I domain-less integrins. The MIDAS motif in beta I domain is flanked by ADMIDAS
      and SyMBS, the other two crucial metal ion binding sites playing pivotal roles in
      the regulation of integrin affinity and bidirectional signaling across the plasma
      membrane. The beta-propeller domain of alpha subunit contains three or four beta
      hairpin loop-like Ca(2+)-binding motifs that have essential roles in integrin
      biogenesis. The function of another Ca(2+)-binding motif located at the genu of
      alpha subunit remains elusive. Here, we provide an overview of the integrin metal
      ion-binding sites and discuss their roles in the regulation of integrin
      functions.

PMID- 22647938
TI  - EpCAM and its potential role in tumor-initiating cells.
AB  - Epithelial cell adhesion molecule EpCAM is expressed on a subset of normal
      epithelia and overexpressed on malignant cells from a variety of different tumor
      entities. This overexpression is even more pronounced on so-called tumor
      initiating cells (TICs) of many carcinomas. Taking this rather ubiquitous
      expression of EpCAM in carcinomas and TICs into account, the question arises how
      EpCAM can serve as a reliable marker for tumor-initiating cells and what might be
      the advantage for TICs to express this molecule. Furthermore, several approaches
      for therapeutic strategies targeting exclusively EpCAM on cancer cells were
      undertaken over the past decades and have recently been transferred to pre
      clinical attempts to eradicate TICs. In the present review, we will depict
      potential functions of EpCAM in tumor cells with a special focus on TICs and
      therapeutic implications.

PMID- 22647939
TI  - Molecular mechanisms underlying adhesion and migration of hematopoietic stem
      cells.
AB  - Hematopoietic stem cell transplantation is the most powerful treatment modality
      for a large number of hematopoietic malignancies, including leukemia. Successful
      hematopoietic recovery after transplantation depends on homing of hematopoietic
      stem cells to the bone marrow and subsequent lodging of those cells in specific
      niches in the bone marrow. Migration of hematopoietic stem cells to the bone
      marrow is a highly regulated process that requires correct regulation of the
      expression and activity of various molecules including chemoattractants,
      selectins and integrins. This review will discuss recent studies that have
      extended our understanding of the molecular mechanisms underlying adhesion,
      migration and bone marrow homing of hematopoietic stem cells.

PMID- 22647942
TI  - Analysis of N'-nitrosonornicotine and its metabolites in rabbit blood with liquid
      chromatography/tandem mass spectrometric method.
AB  - N'-nitrosonornicotine (NNN) is a strong carcinogen. The metabolic study of NNN in
      vivo will help us to further understand it, however, trace detection in complex
      matrices requires highly sensitive detection methods. After the chromatographic
      conditions and mass spectrometric conditions had been optimized and confirmed, a
      method for determining NNN and its metabolites in rabbit blood by high
      performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) was
      established. The results showed that precisions (R.S.Ds) were between 0.5% and
      8.62%, the recoveries ranged from 80% to 111%. Linearity was observed for all
      compounds with detection limits ranging from 0.039 ng mL-1 to 0.217 ng mL-1.
      Metabolic curves and pharmacokinetic parameters were obtained for NNN and its
      metabolites. The elimination half-life of NNN was 30 min and the main metabolite
      of NNN was 4-hydroxy-4-(3-pyridyl)-butyric acid (hydroxy acid) and the major
      metabolic pathway was 5'-hydroxylation and subsequent secondary metabolite
      formation.

PMID- 22647943
TI  - The responses of trichome mutants to enhanced ultraviolet-B radiation in
      Arabidopsis thaliana.
AB  - To gain a better understanding of the protective function of the trichome in
      Arabidopsis against UV-B radiation, we performed a study using several
      Arabidopsis trichome mutants (gl1, gis, gis2, zfp8, try82, and gl3),
      overexpressing trichome positive regulator lines (35S:GIS and 35S:GIS2), and wild
      types (WT) under simulated enhanced UV-B radiation conditions. The flowering
      time, height, diameter of rosette, leaf size, trichome density, and expression
      levels of GL3 gene were measured. Significant decreases in height, diameter of
      rosette, leaf size, and a notable delay in flowering time were observed in all
      mutants and wild-types after exposure to UV-B. Moreover, the trichome density
      showed a significant increase, suggesting a clear induction of trichome formation
      by UV-B. Comparing the mutants and WT, we found that the mutants that had more
      trichomes showed a lower sensitivity to UV-B than the WT, whereas the mutants
      that had fewer trichomes were more sensitive to UV-B. These results indicated
      that the trichome plays a key shielding role against UV-B radiation. qRT-PCR
      analysis indicated that UV-B radiation induced expression of GL3 and an increase
      in GL3 transcript level correlated with the increase in trichome density and,
      suggesting a possible role of GL3 by integrating the environmental signal to
      control trichome initiation.

PMID- 22647944
TI  - Request for articles.

PMID- 22647945
TI  - Obstacles equal opportunity.

PMID- 22647946
TI  - Letter from the President of PSNCB.

PMID- 22647941
TI  - Role of E-cadherin and other cell adhesion molecules in survival and
      differentiation of human pluripotent stem cells.
AB  - The survival, proliferation, self-renewal and differentiation of human
      pluripotent stem cells (hPSCs, including human embryonic stem cells and human
      induced pluripotent stem cells) involve a number of processes that require cell
      cell and cell-matrix interactions. The cell adhesion molecules (CAMs), a group of
      cell surface proteins play a pivotal role in mediating such interactions. Recent
      studies have provided insights into the essential roles and mechanisms of CAMs in
      the regulation of hPSC fate decisions. Here, we review the latest research
      progress in this field and focus on how E-cadherin and several other important
      CAMs including classic cadherins, Ig-superfamily CAMs, integrins and heparin
      sulfate proteoglycans control survival and differentiation of hPSCs.

PMID- 22647940
TI  - Oxygen levels and the regulation of cell adhesion in the nervous system: a
      control point for morphogenesis in development, disease and evolution?
AB  - In this article, I discuss the hallmarks of hypoxia in vitro and in vivo and
      review work showing that many types of stem cell proliferate more robustly in
      lowered oxygen. I then discuss recent studies showing that alterations in the
      levels and the types of cell and substrate adhesion molecules are a notable
      response to reduced O(2) levels in both cultured primary neural stem cells and
      brain tissues in response to hypoxia in vivo. The ability of O(2) levels to
      regulate adhesion molecule expression is linked to the Wnt signaling pathway,
      which can control and be controlled by adhesion events. The ability of O(2)
      levels to influence cell adhesion also has far-reaching implications for
      development, ischemic trauma and neural regeneration, as well as for cancer and
      other diseases. Finally I discuss the possibility that the fluctuations in O(2)
      levels known to have occurred over evolutionary time could, by influencing
      adhesion systems, have contributed to early symbiotic events in unicellular
      organisms and to the emergence of multicellularity. It is not my intention to be
      exhaustive in these domains, which are far from my own field of study. Rather
      this article is meant to provoke and stimulate thinking about molecular evolution
      involving O(2) sensing and signaling during eras of geologic and atmospheric
      change that might inform modern studies on development and disease.

PMID- 22647947
TI  - Growing a medical practice with social media marketing.
AB  - Many medical practices are facing the lack of practice growth that their social
      media efforts are generating. This article provides concrete ideas that can be
      put in place by any medical practice to realize sustainable practice growth
      through social media marketing. In the article, the author demonstrates that
      social media marketing of the medical practice has become absolutely essential in
      today's evolving, competitive, and fast-paced environment. This demonstration is
      made through an exploration of the evolution of what "good" marketing has looked
      like for medical practices over time. In addition, attention is paid to the shift
      in the definition of good marketing that is required for the practice that is
      preparing a social media-marketing plan. Specifically, the article investigates
      the proven requirements for a balanced blend of unique and engaging promotional
      and nonpromotional community outreach, which is required on a daily basis to
      achieve the significant, lasting, and sustainable growth that the practice wishes
      to achieve.

PMID- 22647948
TI  - A synthetical view of pediatrics, lidocaine, and procedural pain relief.
AB  - The clinical efficacy, interventional ease of use, workload implications, and
      cost-effectiveness of using needle-free lidocaine for procedural pain management
      were examined in the pediatric acute care setting. The data from the four studies
      evaluated indicate that needle-free lidocaine significantly reduces procedural
      pain and is a cost-effective alternative to the use of topical lidocaine.

PMID- 22647950
TI  - Protecting the public-discipline hearing, College of Nurses of Ontario.
AB  - This case, #6836613, was heard in the province of Ontario on February 8, 2008.
      Although this case is public knowledge, initials have been used to protect the
      doctor and the clients.

PMID- 22647951
TI  - Proactive practice management will help you avoid disciplinary action.

PMID- 22647952
TI  - Do you need a cell phone policy?

PMID- 22647953
TI  - MROC study: Mastectomy Reconstruction Outcomes Consortium.

PMID- 22647954
TI  - The science behind peptides.
AB  - Compounds consisting of two or more amino acids, or peptides, are the building
      blocks of proteins. Peptides act as transmitters from the brain to the body,
      telling muscles and nerves to perform specific functions. There are multiple
      peptides available that will achieve different topical results.

PMID- 22647955
TI  - Social media-sprint out of the gates!
AB  - Not having a Twitter account or a Facebook fan page for your employer, or for
      yourself, is no longer an option if you plan to participate in social media. I
      preface this article with the statement that many things could possibly change on
      Twitter and Facebook in 1 month's time from writing this article and it's
      publishing. We will focus on Twitter and Facebook because they can have the
      greatest impact with the least amount of effort, and they are the most popular.
      By creating an account for each and connecting them together, you ensure a
      "sprint" out of the social media gate versus a slow jog; so let's get started!

PMID- 22647956
TI  - Wound exudate--the good, the bad, and the ugly.
AB  - Exudate consists of fluid and leukocytes that move to the site of injury from the
      circulatory system in response to local inflammation. This inflammatory response
      leads to blood vessel dilatation and increased permeability, resulting in
      increased production of exudate. The nature and quantity of exudate depend on the
      nature and severity of the tissue damage. The exact amount of wound exudate and
      moisture to promote moist wound healing is unknown. This moisture balance is
      essential to promote healing and is oftentimes a major challenge to the wound
      care provider. This article will explore the benefits of wound fluid as well as
      the detrimental impact on wound healing. Assessment and management will also be
      briefly discussed.

PMID- 22647957
TI  - Emergency preparedness case study:  malignant hyperthermia.
AB  - The second of this 2012 Case Study series addresses a situation that is uncommon
      in the surgical setting. Without proper recognition and prompt treatment, the
      mortality rate can be as high as 80% (Christiansen & Collins, 2004; Larach,
      Gronert, Allen, Brandom, & Lehman, 2010). With prompt recognition and
      intervention when this emergency does arise, the mortality rate has been reduced
      to 5% ((Rosenberg, Sambuughin, & Dirksen, 2010). Malignant hyperthermia (MH) is
      an inherited syndrome that affects 1 of 50,000 adults and 1 of 15,000 pediatric
      patients undergoing anesthetic procedures (Christiansen & Collins, 2004;
      Rosenberg et al., 2010). In this article, the reader is exposed to a case of MH
      and is asked a series of questions related to risk assessment, signs and
      symptoms, and nursing responsibilities.

PMID- 22647959
TI  - Role of microRNAs and other sRNAs of plants in their changing environments.
AB  - Plants constantly face a complex array of environmental biotic and abiotic
      stimuli. Recent studies in various plants have highlighted the key roles of
      microRNAs and of different siRNA classes in the post-transcriptional regulation
      of plant genes essential for conserved responses of plants to individual stress
      conditions. It is not yet clear how these different signals and responses are
      integrated in nature. In the present review, we summarize current knowledge on
      sRNA-mediated responses to stress, and highlight possible directions of future
      research.

PMID- 22647961
TI  - (2)(infinity)[Co{1,4-C6H4(CN)2}2{NTf2}2][SnI{Co(CO)4}3](2)--a 2D coordination
      network with an intercalated carbonyl cluster.
AB  - Dark red transparent crystals of [Co{1,4
      C(6)H(4)(CN)(2)}(2){NTf(2)}(2)][SnI{Co(CO)(4)}(3)](2) are obtained by reacting
      SnI(4), Co(2)(CO)(8) and 1,4-C(6)H(4)(CN)(2) in the ionic liquid [EMIm][NTf(2)]
      (EMIm: 1-ethyl-3-methylimidazolium; NTf(2): bis(trifluoromethylsulfonyl)imide).
      According to X-ray structure analysis based on single crystals, the title
      compound crystallizes in a triclinic manner and contains the novel
      (2)(infinity)[Co{1,4-C(6)H(4)(CN)(2)}(2){NTf(2)}(2)] coordination network. This
      infinite 2D network is composed of Co(2+) ions that are planarily interlinked by
      four 1,4-dicyanobenzene ligands. As a non-charged 2D network, Co(2+) is
      furthermore coordinated by two [NTf(2)](-) anions. The (2)(infinity)[Co{1,4
      C(6)H(4)(CN)(2)}(2){NTf(2)}(2)] layers are stacked on top of each other with
      SnI[Co(CO)(4)](3) molecules intercalated in distorted cubic gaps between the
      layers. The title compound is furthermore characterized by energy dispersive X
      ray (EDX) analysis, thermogravimetry (TG), infrared spectroscopy (FT-IR) and
      optical spectroscopy (UV-Vis).

PMID- 22647960
TI  - Analysis of apoplastic and symplastic antioxidant system in shallot leaves:
      impacts of weak static electric and magnetic field.
AB  - Impacts of electric and magnetic fields (EFs and MFs) on a biological organism
      vary depending on their application style, time, and intensities. High intensity
      MF and EF have destructive effects on plants. However, at low intensities, these
      phenomena are of special interest because of the complexity of plant responses.
      This study reports the effects of continuous, low-intensity static MF (7 mT) and
      EF (20 kV/m) on growth and antioxidant status of shallot (Allium ascalonicum L.)
      leaves, and evaluates whether shifts in antioxidant status of apoplastic and
      symplastic area help plants to adapt a new environment. Growth was induced by MF
      but EF applied emerged as a stress factor. Despite a lack of visible symptoms of
      injury, lipid peroxidation and H2O2 levels increased in EF applied leaves.
      Certain symplastic antioxidant enzyme activities and non-enzymatic antioxidant
      levels increased in response to MF and EF applications. Antioxidant enzymes in
      the leaf apoplast, by contrast, were found to show different regulation responses
      to EF and MF. Our results suggest that apoplastic constituents may work as
      potentially important redox regulators sensing and signaling environmental
      changes. Static continuous MF and EF at low intensities have distinct impacts on
      growth and the antioxidant system in plant leaves, and weak MF is involved in
      antioxidant-mediated reactions in the apoplast, resulting in overcoming a
      possible redox imbalance.

PMID- 22647962
TI  - Applying empirical methods in clinical practice: introducing the model for
      assessing treatment effect.
AB  - BACKGROUND: One challenge in rehabilitation is determining whether improvement in
      the patient is a treatment-specific effect or due to extraneous factors (eg, the
      passage of time, spontaneous recovery). DESIGN: Descriptive, model building, and
      2 cases illustrating the model. METHOD: The Model for Assessing Treatment Effect
      (MATE) incorporates the conceptual frameworks of the International Classification
      of Functioning, Disability, and Health (ICF), along with single-case experimental
      methodology. RESULTS: The MATE contains 7 levels organized in a hierarchy,
      representing (i) increasing specificity of evaluation procedures and (ii) control
      of extraneous variables during therapy. Two illustrative cases of patients with
      traumatic brain injury undergoing inpatient rehabilitation for, inter alia,
      cognitive-communication impairments are described to illustrate common clinical
      practice (level 2 of MATE) and a superior method using a multiple-baseline design
      across behaviors, enabling rigorous evaluation of treatment effect (level 6 of
      MATE). CONCLUSIONS: The MATE offers a systematic, evidence-based approach for
      implementing ICF-informed goals into clinical practice. It also provides a
      benchmark against which a clinical service can be evaluated in terms of the rigor
      of its therapy program.

PMID- 22647963
TI  - Self-reported mild TBI and postconcussive symptoms in a peacetime active duty
      military population: effect of multiple TBI history versus single mild TBI.
AB  - OBJECTIVE: To investigate the potential cumulative impact of mild traumatic brain
      injury (MTBI) on postconcussive symptoms. PARTICIPANTS: A total of 224 active
      duty soldiers reporting MTBI within 1 year of testing. For 101, this MTBI was
      their only reported traumatic brain injury (TBI); 123 had sustained at least 1
      additional MTBI during their lifetime. A No TBI control group (n = 224) was
      included for comparison. MAIN MEASURE: Self-report symptoms data via
      questionnaire. Within time since injury subgroups (<=3 months; Post-3 months),
      symptom endorsement (no symptoms, 1 or 2 symptoms, 3+ symptoms) among soldiers
      with 1 MTBI was compared with that of soldiers with 2 or more MTBIs. Injured
      soldiers' symptom endorsement was compared with that of soldiers who had not
      sustained a TBI. RESULTS: Among the recently injured (<=3 months), those with 2
      or more MTBIs endorsed significantly more symptoms than those with 1 MTBI: 67% of
      soldiers with 2 or more MTBIs reported 3+ symptoms, versus 29% of One MTBI
      soldiers. Among Post-3 month soldiers, there were no significant differences
      between MTBI groups. Overall, soldiers with MTBI endorsed significantly more
      symptoms than those without TBI. CONCLUSION: Past experience of MTBI may be a
      risk factor for increased symptom difficulty for several months postinjury.
      Clinicians should ascertain lifetime history of brain injury when evaluating
      patients for MTBI.

PMID- 22647964
TI  - Identification of transient altered consciousness induced by military-related
      blast exposure and its relation to postconcussion symptoms.
AB  - BACKGROUND: The ongoing controversy whether mild traumatic brain injury (TBI) can
      cause chronic sequel is partly due to diagnostic limitations. Diagnosing mild TBI
      is particularly challenging when assessment is not immediate, and when informed,
      first responder documentation or witness corroboration is absent. In this common
      scenario, the diagnosis is made entirely on self-report of an initial period of
      alteration of consciousness (AOC) associated with a plausible injury mechanism.
      Yet, there is scant published empirical guidance on methods for accurately
      detecting historical AOC. OBJECTIVES: To assess the value that recalled AOC
      symptoms collected via questionnaire have in evaluating individuals exposed to
      blast during recent military deployment. More specifically, to analyze the
      concrete AOC items (those signifying unconsciousness and/or posttraumatic
      amnesia) for their (1) frequency and distribution of positive versus negative
      responses, (2) interitem agreement, and (3) relation to current neuropsychiatric
      symptoms including those consistent with postconcussion syndrome (PCS).
      PARTICIPANTS: Eighty-seven active duty or Veteran subjects who experienced acute
      effects from a blast within the past 2 years while deployed for Operations
      Enduring and Iraqi Freedom. RESULTS: : Twenty-nine participants (33.3%) responded
      positively to at least 1 of 3 concrete AOC items: gap in memory (17.2%), memory
      not continuous (13.8%), and/or told by observer they had loss of consciousness
      (20.7%). Alteration of consciousness items were associated with but
      nondiscriminate of current symptom distress on standardized measures of PCS
      (Rivermead Postconcussion Symptom Questionnaire), posttraumatic stress disorder
      (PTSD; PTSD Checklist), depression (Centers for Epidemiological Studies
      Depression Scale), and pain (Short Form McGill Pain Questionnaire). CONCLUSIONS:
      The positive association between subjects' questionnaire-based AOC item responses
      and current symptom complex measures suggests that mild TBI has a role in the
      development of chronic neuropsychiatric symptoms after blast exposure. The lack
      of symptom- complex discrimination, and the inconsistencies found in subjects'
      item responses suggest that a structured interview may improve postacute
      diagnostic specificity for mild TBI.

PMID- 22647965
TI  - The relation between posttraumatic stress disorder and mild traumatic brain
      injury acquired during Operations Enduring Freedom and Iraqi Freedom.
AB  - OBJECTIVE: To understand the relations of mild traumatic brain injury (TBI),
      blast exposure, and brain white matter structure to severity of posttraumatic
      stress disorder (PTSD). DESIGN: Nested cohort study using multivariate analyses.
      PARTICIPANTS: Fifty-two OEF/OIF veterans who served in combat areas between 2001
      and 2008 were studied approximately 4 years after the last tour of duty. MAIN
      MEASURES: PTSD Checklist-Military; Combat Experiences Survey, interview questions
      concerning blast exposure and TBI symptoms; anatomical magnetic resonance imaging
      (MRI), and diffusion tensor imaging (DTI) scanning of the brain. RESULTS: PTSD
      severity was associated with higher 1st percentile values of mean diffusivity on
      DTI (regression coefficient [r] = 4.2, P = .039), abnormal MRI (r = 13.3, P =
      .046), and the severity of exposure to combat events (r = 5.4, P = .007). Mild
      TBI was not significantly associated with PTSD severity. Blast exposure was
      associated with lower 1st percentile values of fractional anisotropy on DTI (odds
      ratio [OR] = 0.38 per SD; 95% confidence interval [CI], 0.15-0.92), normal MRI
      (OR = 0.00, 95% likelihood ratio test CI, 0.00-0.09), and the severity of
      exposure to traumatic events (OR = 3.64 per SD; 95% CI, 1.40-9.43). CONCLUSIONS:
      PTSD severity is related to both the severity of combat stress and underlying
      structural brain changes on MRI and DTI but not to a clinical diagnosis of mild
      TBI. The observed relation between blast exposure and abnormal DTI suggests that
      subclinical TBI may play a role in the genesis of PTSD in a combat environment.

PMID- 22647966
TI  - Self-selected walking speed predicts ability to run following traumatic brain
      injury.
AB  - OBJECTIVE: To identify factors that predict running ability following traumatic
      brain injury (TBI), and to quantify performance thresholds for these predictors.
      DESIGN: Cross-sectional cohort study. PARTICIPANTS: One hundred fourteen people
      with TBI. OUTCOME MEASURES: Self-selected walking speed, the high-level mobility
      assessment tool, postural stability (lateral center of mass displacement), ankle
      power generation at push-off and quality of gait performance (Gait Profile
      Score). RESULTS: All predictor variables were all strongly associated with the
      ability to run. However, only self-selected walking speed contributed
      significantly to the final result. Investigation of performance thresholds for
      self-selected walking speed indicated that following TBI, people who walk at
      speeds of 1.0 m/s or higher are 16.9 times more likely of being able to run than
      for those who walk at speeds of less than 1.0 m/s. CONCLUSIONS: Self-selected
      walking speeds higher than 1.0 m/s greatly increase the likelihood of running
      following brain injury. The 1.0 m/s threshold, although slower than able-bodied
      self-selected walking speeds, may be an important indicator of the ability to run
      in this population.

PMID- 22647967
TI  - Quantification accuracy and partial volume effect in dependence of the
      attenuation correction of a state-of-the-art small animal PET scanner.
AB  - Quantification accuracy and partial volume effect (PVE) of the Siemens Inveon PET
      scanner were evaluated. The influence of transmission source activities (40 and
      160 MBq) on the quantification accuracy and the PVE were determined. Dynamic
      range, object size and PVE for different sphere sizes, contrast ratios and
      positions in the field of view (FOV) were evaluated. The acquired data were
      reconstructed using different algorithms and correction methods. The activity
      level of the transmission source and the total emission activity in the FOV
      strongly influenced the attenuation maps. Reconstruction algorithms, correction
      methods, object size and location within the FOV had a strong influence on the
      PVE in all configurations. All evaluated parameters potentially influence the
      quantification accuracy. Hence, all protocols should be kept constant during a
      study to allow a comparison between different scans.

PMID- 22647968
TI  - FGF23 acts directly on renal proximal tubules to induce phosphaturia through
      activation of the ERK1/2-SGK1 signaling pathway.
AB  - Fibroblast growth factor-23 (FGF23) is a bone-derived endocrine regulator of
      phosphate homeostasis which inhibits renal tubular phosphate reabsorption.
      Binding of circulating FGF23 to FGF receptors in the cell membrane requires the
      concurrent presence of the co-receptor alphaKlotho. It is still controversial
      whether alphaKlotho is expressed in the kidney proximal tubule, the principal
      site of phosphate reabsorption. Hence, it has remained an enigma as to how FGF23
      downregulates renal phosphate reabsorption. Here, we show that renal proximal
      tubular cells do express the co-receptor alphaKlotho together with cognate FGF
      receptors, and that FGF23 directly downregulates membrane expression of the
      sodium-phosphate cotransporter NaPi-2a by serine phosphorylation of the
      scaffolding protein Na(+)/H(+) exchange regulatory cofactor (NHERF)-1 through
      ERK1/2 and serum/glucocorticoid-regulated kinase-1 signaling.

PMID- 22647969
TI  - Aortic root aneurysm in an adult patient with aortic coarctation: a single-stage
      approach.
AB  - Coarctation of the aorta is a common congenital defect that may be undiagnosed
      until adulthood. Moreover, coarctation is associated with congenital and acquired
      cardiac pathology that may require surgical intervention. The management of an
      adult patient with aortic coarctation and an associated cardiac defect poses a
      great technical challenge since there are no standard guidelines for the therapy
      of such a complex pathology. Several extra-anatomic bypass grafting techniques
      have been described, including methods in which distal anastomosis is performed
      on the descending thoracic aorta, allowing simultaneous intracardiac repair. We
      report here a 37-year old man who was diagnosed with an aortic root aneurysm and
      aortic coarctation. The patient was treated electively with a single-stage
      approach through a median sternotomy that consisted of valve-sparing replacement
      of the aortic root and ascending-to-descending extra-anatomic aortic bypass,
      using a 18-mm Dacron graft. Firstly, the aortic root was replaced with the Yacoub
      remodelling procedure, and then the distal anastomosis was performed to the
      descending aorta, behind the heart, with the posterior pericardial approach. The
      extra-anatomic bypass graft was brought laterally from the right atrium and
      implanted in the ascending graft. Postoperative recovery was uneventful and a
      control computed tomographic angiogram 1 month after complete repair showed good
      results.

PMID- 22647970
TI  - Extracorporeal life support in the acute management of tumour lysis syndrome.
AB  - A 16-month old boy presented with a severe tumour lysis syndrome (TLS)
      complicating induction therapy for acute myeloid leukaemia. This was further
      complicated by a respiratory syncytial virus infection. The failure of response
      to escalating treatment necessitated the use of extracorporeal life support
      (ECLS) during continuation of his induction chemotherapy. He was weaned from
      support after the resolution of the TLS and completed chemotherapy successfully.
      ECLS may have a role to play in the acute support of children with
      cardiorespiratory failure as a result of malignancy or the required treatment.

PMID- 22647972
TI  - Prognostic and predictive biomarkers for epidermal growth factor receptor
      targeted therapy in colorectal cancer: beyond KRAS mutations.
AB  - The advent of the epidermal growth factor receptor (EGFR)-targeted monoclonal
      antibodies (mAbs), cetuximab and panitumumab has expanded the range of treatment
      options for metastatic colorectal cancer (CRC). Despite these agents have paved
      the way to individualized therapy, our understanding why some patients respond to
      treatment whereas others do not remain poor. The realization that detection of
      positive EGFR expression by IHC does not reliably predict clinical outcome of
      EGFR-targeted treatment has led to an intense search for alternative predictive
      biomarkers. Data derived from multiple phase III trials have indicated that KRAS
      mutations can be considered a highly specific negative biomarker of benefit to
      anti-EGFR mAbs. Oncologists are now facing emerging issues in the treatment of
      metastatic CRC, including the identification of additional genetic determinants
      of primary resistance to EGFR-targeted therapy for further improving selection of
      patients, the explanation of rare cases of patients carrying KRAS-mutated tumours
      who have been reported to respond to cetuximab and panitumumab and the discovery
      of mechanisms of secondary resistance to EGFR-targeted therapy. Current data
      suggest that, together with KRAS mutations, the evaluation of EGFR gene copy
      number (GCN), BRAF, NRAS, PIK3CA mutations or loss of PTEN expression could also
      be useful for selecting patients with reduced chance to benefit from anti-EGFR
      mAbs. This review aims to provide an updated of the most recent data on
      predictive and prognostic biomarkers within the EGFR pathway, the challenges this
      emerging field presents and the future role of these molecular markers in CRC
      treatment.

PMID- 22647971
TI  - Epicardial left atrial appendage clip occlusion also provides the electrical
      isolation of the left atrial appendage.
AB  - OBJECTIVES: The exclusion of the left atrial appendage (LAA) has been used to
      reduce the risk of stroke associated with atrial fibrillation (AF). While LAA
      exclusion has been associated with a reduced risk of stroke, the effect on the
      electrical activity of the LAA (a potential source of AF) remains unknown. As
      such, we sought to demonstrate whether surgical epicardial clip occlusion leads
      to the electrical isolation of the LAA. METHODS: From December 2010 until August
      2011, 10 patients with paroxysmal AF underwent off-pump coronary artery bypass
      surgery with bilateral pulmonary vein isolation and an LAA clip occlusion with a
      new epicardial clip. Before and after the clip was placed, pacing manoeuvres were
      performed to assess the electrical exit and entry blocks from the LAA. RESULTS:
      All clips were applied successfully. The mean procedure time for the clip
      application was 4 +/- 1 min. No complications occurred related to clip
      application. Prior to the pericardial closure, 18 +/- 3 min after the clip
      placement, the LAA stimulation and pacing manoeuvres demonstrated complete
      electrical isolation of the LAA in all cases. CONCLUSIONS: Epicardial LAA clip
      occlusion leads to the acute electrical isolation of the LAA and may not only
      provide stroke prevention but also reduce the recurrence of AF.

PMID- 22647973
TI  - Automated analysis of single stem cells in microfluidic traps.
AB  - We report a reliable strategy to perform automated image cytometry of single (non
      adherent) stem cells captured in microfluidic traps. The method rapidly segments
      images of an entire microfluidic chip based on the detection of horizontal edges
      of microfluidic channels, from where the position of the trapped cells can be
      derived and the trapped cells identified with very high precision (>97%). We used
      this method to successfully quantify the efficiency and spatial distribution of
      single-cell loading of a microfluidic chip comprised of 2048 single-cell traps.
      Furthermore, cytometric analysis of trapped primary hematopoietic stem cells
      (HSC) faithfully recapitulated the distribution of cells in the G1 and S/G2-M
      phase of the cell cycle that was measured by flow cytometry. This approach should
      be applicable to automatically track single live cells in a wealth of
      microfluidic systems.

PMID- 22647974
TI  - Molecular imaging of thrombus: technology in evolution.

PMID- 22647975
TI  - Novel single-chain antibody-targeted microbubbles for molecular ultrasound
      imaging of thrombosis: validation of a unique noninvasive method for rapid and
      sensitive detection of thrombi and monitoring of success or failure of
      thrombolysis in mice.
AB  - BACKGROUND: Molecular imaging is a fast emerging technology allowing noninvasive
      detection of vascular pathologies. However, imaging modalities offering high
      resolution currently do not allow real-time imaging. We hypothesized that
      contrast-enhanced ultrasound with microbubbles (MBs) selectively targeted to
      activated platelets would offer high-resolution, real-time molecular imaging of
      evolving and dissolving arterial thrombi. METHODS AND RESULTS: Lipid-shell based
      gas-filled MBs were conjugated to either a single-chain antibody specific for
      activated glycoprotein IIb/IIIa via binding to a Ligand-Induced Binding Site
      (LIBS-MBs) or a nonspecific single-chain antibody (control MBs). Successful
      conjugation was assessed in flow cytometry and immunofluorescence double
      staining. LIBS-MBs but not control MBs strongly adhered to both immobilized
      activated platelets and microthrombi under flow. Thrombi induced in carotid
      arteries of C57Bl6 mice in vivo by ferric chloride injury were then assessed with
      ultrasound before and 20 minutes after MB injection through the use of gray-scale
      area intensity measurement. Gray-scale units converted to decibels demonstrated a
      significant increase after LIBS-MB but not after control MB injection (9.55+/-1.7
      versus 1.46+/-1.3 dB; P<0.01). Furthermore, after thrombolysis with urokinase,
      LIBS-MB ultrasound imaging allows monitoring of the reduction of thrombus size
      (P<0.001). CONCLUSION: We demonstrate that glycoprotein IIb/IIIa-targeted MBs
      specifically bind to activated platelets in vitro and allow real-time molecular
      imaging of acute arterial thrombosis and monitoring of the success or failure of
      pharmacological thrombolysis in vivo.

PMID- 22647976
TI  - Cardiomyocytes derived from pluripotent stem cells recapitulate
      electrophysiological characteristics of an overlap syndrome of cardiac sodium
      channel disease.
AB  - BACKGROUND: Pluripotent stem cells (PSCs) offer a new paradigm for modeling
      genetic cardiac diseases, but it is unclear whether mouse and human PSCs can
      truly model both gain- and loss-of-function genetic disorders affecting the Na(+)
      current (I(Na)) because of the immaturity of the PSC-derived cardiomyocytes. To
      address this issue, we generated multiple PSC lines containing a Na(+) channel
      mutation causing a cardiac Na(+) channel overlap syndrome. METHOD AND RESULTS:
      Induced PSC (iPSC) lines were generated from mice carrying the Scn5a(1798insD/+)
      (Scn5a-het) mutation. These mouse iPSCs, along with wild-type mouse iPSCs, were
      compared with the targeted mouse embryonic stem cell line used to generate the
      mutant mice and with the wild-type mouse embryonic stem cell line. Patch-clamp
      experiments showed that the Scn5a-het cardiomyocytes had a significant decrease
      in I(Na) density and a larger persistent I(Na) compared with Scn5a-wt
      cardiomyocytes. Action potential measurements showed a reduced upstroke velocity
      and longer action potential duration in Scn5a-het myocytes. These characteristics
      recapitulated findings from primary cardiomyocytes isolated directly from adult
      Scn5a-het mice. Finally, iPSCs were generated from a patient with the equivalent
      SCN5A(1795insD/+) mutation. Patch-clamp measurements on the derivative
      cardiomyocytes revealed changes similar to those in the mouse PSC-derived
      cardiomyocytes. CONCLUSION: Here, we demonstrate that both embryonic stem cell-
      and iPSC-derived cardiomyocytes can recapitulate the characteristics of a
      combined gain- and loss-of-function Na(+) channel mutation and that the
      electrophysiological immaturity of PSC-derived cardiomyocytes does not preclude
      their use as an accurate model for cardiac Na(+) channel disease.

PMID- 22647977
TI  - Forever young: induced pluripotent stem cells as models of inherited arrhythmias.

PMID- 22647978
TI  - Donation of 'spare' fresh or frozen embryos to research: who decides that an
      embryo is 'spare' and how can we enhance the quality and protect the validity of
      consent?
AB  - This paper analyses elements of the legal process of consent to the donation of
      'spare' embryos to research, including stem-cell research, and makes a
      recommendation intended to enhance the quality of that process, including on
      occasion by guarding against the invalidity of such consent. This is important in
      its own right and also so as to maximise the reproductive treatment options of
      couples engaged in in vitro fertilisation (IVF) treatment and to avoid possible
      harms to them. In Part 1, with reference to qualitative data from three UK IVF
      clinics, we explore the often delicate and contingent nature of what comes to be,
      for legal purposes, a 'spare' embryo. The way in which an embryo becomes 'spare',
      with its implications for the process of consent to donation to research, is not
      addressed in the relevant reports relating to or codes of practice governing the
      donation of embryos to research, which assume an unproblematic notion of the
      'spare' embryo. Significantly, our analysis demonstrates that there is an
      important and previously unrecognised first stage in the donation of a 'spare'
      embryo to research, namely: consent to an embryo being 'spare' and so, at the
      same time, to its disuse in treatment. This is not explicitly covered by the
      Human Fertilisation and Embryology (HFE) Act 1990, as amended by the HFE Act
      2008. Having identified this important initial stage in the process of consent to
      the donation of a 'spare' embryo to research in conclusion to Part 1, in Part 2
      we analyse the idea of consent to an embryo's disuse in treatment on the basis
      that it is 'spare' with reference to the legal elements of consent, namely
      information as to nature and purpose, capacity, and voluntariness. We argue that
      there are in fact three related consent processes in play, of which the principal
      one concerns consent to an embryo's disuse in treatment. If the quality of this
      first consent is compromised, in turn this will impact on the quality of the
      consent to the donation of that 'spare' embryo to research, followed by the
      quality of consent to future cycles of assisted reproduction treatment in the
      event that these are needed as a result of a donation decision. The analysis
      overall is of central relevance to the debate as to whether, and if so when, it
      should be permissible to request the donation of fresh embryos for research, as
      opposed to those that have been frozen and, for instance, have reached the end of
      their statutory storage term. This has a particular bearing on the donation of
      embryos to stem-cell research since there is a debate as to whether fresh embryos
      are most useful for this.

PMID- 22647979
TI  - Formation of N-heterocyclic diphosphine ligands from Ag(I)-assisted condensation
      reactions between bdppeda and formaldehyde and their binuclear silver(I)
      complexes.
AB  - The reaction of [Ag(MeCN)(4)]ClO(4) with N,N,N',N'
      tetra(diphenylphosphanylmethyl)ethylenediamine (dppeda) in CH(2)Cl(2)/MeOH
      afforded an unexpected cationic binuclear complex [Ag(2)(L(1))(2)(eta,eta-MU
      ClO(4))(2)](ClO(4))(2) (L(1) = N,N'-bis(diphenylphosphanylmethyl)-3H-4,5
      dihydroimidazole-1-ium) (1). Compound 1 was also prepared in high yield from
      reactions of [Ag(MeCN)(4)]ClO(4) with N,N'
      bis(diphenylphosphanylmethyl)ethylenediamine (bdppeda) in the presence of
      formaldehyde (HCHO) or formic acid (HCOOH). Analogous reactions of AgCl with
      bdppeda and HCHO resulted in the formation a neutral binuclear complex
      [Ag(2)(L(2))(2)(MU-Cl)(2)] (L(2) = N,N-bis(diphenylphosphanylmethyl)
      tetrahydroimidazole) (2). Treatment of 1 with concentrated HCl gave rise to a
      partially anion-exchanged product [Ag(2)(L(1))(2)(MU-Cl)(2)](ClO(4))(2) (3).
      Compounds 1 and 3 have a similar cationic binuclear structure, in which a
      [Ag(2)(eta,eta-MU-ClO(4))(2)] or [Ag(2)(MU-Cl)(2)] ring is sandwiched by two in
      situ-formed cationic L(1) ligands. The L(1) ligand may be generated by the Ag(I)
      assisted condensation reaction between bdppeda and HCHO or HCOOH. Compound 2
      holds a neutral binuclear structure, in which a [Ag(2)(MU-Cl)(2)] ring is
      connected by two in situ-formed L(2) ligands from its top and bottom sites. The
      neutral ligand L(2) may be produced from another Ag(I)-assisted condensation
      reaction between bdppeda and HCHO. The in situ formation of the L(1) and L(2)
      ligands provides a new route to the N-heterocyclic diphosphine ligands, and an
      interesting insight into the coordination chemistry of their metal complexes.

PMID- 22647980
TI  - Eliminating central line-associated blood stream infections: progress continues
      on a national patient safety imperative.

PMID- 22647981
TI  - Interprofessional simulation on nurse interruptions.
AB  - This project was an initial attempt to help nonnurses who will potentially work
      in the health care field to gain an understanding of the impact of distractions
      and interruptions on nurses. Graduate students in the Institute for Health Care
      Improvement Open School participated in an unfolding simulation in a hospital
      setting to expose them to the challenges of providing care in a work environment
      that often includes multiple interruptions.

PMID- 22647983
TI  - Thanking veterans across decades, miles, and geography and emergency preparedness
      begins now.

PMID- 22647984
TI  - Simple "frailty" test predicts kidney transplant outcome:gauge of physical
      reserve not just for elderly.

PMID- 22647982
TI  - Monitoring autophagic flux by an improved tandem fluorescent-tagged LC3 (mTagRFP
      mWasabi-LC3) reveals that high-dose rapamycin impairs autophagic flux in cancer
      cells.
AB  - Monitoring autophagic flux is important for the analysis of autophagy. Tandem
      fluorescent-tagged LC3 (mRFP-EGFP-LC3) is a convenient assay for monitoring
      autophagic flux based on different pH stability of EGFP and mRFP fluorescent
      proteins. However, it has been reported that there is still weak fluorescence of
      EGFP in acidic environments (pH between 4 and 5) or acidic lysosomes. So it is
      possible that autolysosomes are labeled with yellow signals (GFP(+)RFP(+)
      puncta), which results in misinterpreting autophagic flux results. Therefore, it
      is desirable to choose a monomeric green fluorescent protein that is more acid
      sensitive than EGFP in the assay of autophagic flux. Here, we report on an
      mTagRFP-mWasabi-LC3 reporter, in which mWasabi is more acid sensitive than EGFP
      and has no fluorescence in acidic lysosomes. Meanwhile, mTagRFP-mWasabi-LC3DeltaG
      was constructed as the negative control for this assay. Compared with mRFP-EGFP
      LC3, our results showed that this reporter is more sensitive and accurate in
      detecting the accumulation of autophagosomes and autolysosomes. Using this
      reporter, we find that high-dose rapamycin (30 MUM) will impair autophagic flux,
      inducing many more autophagosomes than autolysosomes in HeLa cells, while low
      dose rapamycin (500 nM) has an opposite effect. In addition, other chemical
      autophagy inducers (cisplatin, staurosporine and Z18) also elicit much more
      autophagosomes at high doses than those at low doses. Our results suggest that
      the dosage of chemical autophagy inducers would obviously influence autophagic
      flux in cells.

PMID- 22647985
TI  - One hospice's project to honor and care for veterans.
AB  - This article explains Hospice of Dayton's program to care for veterans at end-of
      life using 2 case studies as examples. Instructions, opportunities, and the
      unique challenges for support and care of this population at end-of-life are
      illustrated.

PMID- 22647986
TI  - Patient care heart failure model: the hospitalization to home plan of care.
AB  - This article details a heart failure care model at North East Veterans Affairs
      (VA) Medical Center. The North East VA health system has been involved in quality
      improvement of heart failure care for many years. This involves continuous
      quality improvement in the full spectrum of treatment from admission through
      discharge and outpatient follow-up. Improving patient care is always the main
      goal. Assisting patients to better understand self-care concepts is key to
      avoiding heart failure exacerbations. Educating patients to identify problematic
      symptoms early and access the system for help can often avoid costly
      readmissions. The case study provided in this article highlights the journey of a
      heart failure patient treated at this VA hospital and the care coordination
      process, which is necessary for good patient care through use of
      multidisciplinary team members.

PMID- 22647987
TI  - Transcultural nursing course in Tanzania, Africa.
AB  - A transcultural nursing course in Tanzania was offered in fall 2010 at Williston
      State College, located in North Dakota. Madeleine Leininger's Culture Care:
      Diversity and Universality Theory (Principles of Developing Cultural Competence)
      was the framework used for the experience. The course provided nursing students
      the opportunity to learn about the culture, health, and illness beliefs of
      Tanzanians; their values and practices; the prevalence of HIV/AIDS; and the
      differences and similarities between the healthcare systems, hospice/palliative
      care, and home visits in Tanzania as compared to the United States.

PMID- 22647989
TI  - How can we "join forces" for our veterans?

PMID- 22647990
TI  - Emergency preparedness: how Hurricane Irene caught my community unprepared.

PMID- 22647991
TI  - Risk factors for cage retropulsion after posterior lumbar interbody fusion:
      analysis of 1070 cases.
AB  - STUDY DESIGN: Single-center retrospective study. OBJECTIVE: We examined the risk
      factors for cage retropulsion after posterior lumbar interbody fusion (PLIF)
      performed for patients with degenerative lumbar spinal diseases. SUMMARY OF
      BACKGROUND DATA: Although PLIF is a widely accepted procedure, problems remain
      regarding perioperative and postoperative complications. There are few reported
      studies identifying specific risk factors for cage retropulsion, one of the
      implant-related complications after PLIF, although several case reports have been
      published. METHODS: Between April 2006 and July 2010, 1070 patients with various
      degenerative lumbar spinal diseases underwent single- or multilevel PLIF combined
      with posterolateral fusion, using posterior pedicle screw fixation and box-type
      cages. Their medical records and preoperative radiographs were reviewed and the
      factors influencing the incidence of cage retropulsion were analyzed. RESULTS:
      There were 9 cases of cage retropulsion (7 men and 2 women; mean age, 68.2 yr),
      and it developed within 2 months after surgery in all cases. Five patients had
      low back pain or leg pain, 3 of whom required revision surgery. The mean fusion
      level was 3.9 (range, 2-5); in 6 of the 9 patients, the cage had migrated at
      L5/S, 2 at L4/5, and 1 at L3/4. All of the cages were inserted at the end disc
      level of multilevel fusion procedures. The disc heights and ranges of motion were
      significantly greater in patients with cage retropulsion, and patients with a
      pear-shaped disc space also showed a higher rate of cage retropulsion.
      CONCLUSION: These results indicate that PLIF at L5/S, a wide disc space with
      instability, multilevel fusion surgery, and a pear-shaped disc space on lateral
      radiographs are risk factors for cage retropulsion. The identification of these
      risk factors should allow us to avoid this complication, and the use of
      expandable cages is an effective option for such cases.

PMID- 22647996
TI  - Ischemic heart disease in women. Data from BARIHD study.

PMID- 22647997
TI  - Percutaneous treatment of superior vena cava syndrome after pacemakers electrodes
      implantation and/or surgical correction of congenital heart disease.

PMID- 22647999
TI  - FeCl3 promoted highly regioselective [3 + 2] cycloaddition of dimethyl 2-vinyl
      and aryl cyclopropane-1,1-dicarboxylates with aryl isothiocyanates.
AB  - A FeCl(3) promoted [3 + 2] annulation of dimethyl 2-vinyl and arylcyclopropane
      1,1-dicarboxylate with aryl isothiocyanates has been developed to give
      pyrrolidine-2-thiones in good yields with high regioselectivity.

PMID- 22648000
TI  - Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss
      induced by modeled microgravity in rats.
AB  - Treatment with molecular hydrogen alleviates microgravity-induced bone loss
      through abating oxidative stress, restoring osteoblastic differentiation, and
      suppressing osteoclast differentiation and osteoclastogenesis. INTRODUCTION:
      Recently, it has been suggested that hydrogen gas exerts a therapeutic
      antioxidant activity by selectively reducing cytotoxic reactive oxygen species
      (ROS). The aim of the present study was to elucidate whether treatment with
      molecular hydrogen alleviated bone loss induced by modeled microgravity in rats.
      METHODS: Hindlimb suspension (HLS) and rotary wall vessel bioreactor were used to
      model microgravity in vivo and in vitro, respectively. Sprague-Dawley rats were
      exposed to HLS for 6 weeks to induced bone loss and simultaneously administrated
      with hydrogen water (HW). Then, we investigated the effects of incubation with
      hydrogen-rich medium (HRM) on MC3T3-E1 and RAW264.7 cells exposed to modeled
      microgravity. RESULTS: Treatment with HW alleviated HLS-induced reduction of bone
      mineral density, ultimate load, stiffness, and energy in femur and lumbar
      vertebra. Treatment with HW alleviated HLS-induced augmentation of
      malondialdehyde content and peroxynitrite content and reduction of total
      sulfhydryl content in femur and lumbar vertebra. In cultured MC3T3-E1 cells,
      incubation with HRM inhibited modeled microgravity-induced ROS formation,
      reduction of osteoblastic differentiation, increase of ratio of receptor
      activator of nuclear factor kappa B ligand to osteoprotegerin, inducible nitric
      oxide synthetase upregulation, and Erk1/2 phosphorylation. In cultured RAW264.7,
      incubation with HRM aggravated modeled microgravity-induced ROS formation,
      osteoclastic differentiation, and osteoclastogenesis. CONCLUSION: Treatment with
      molecular hydrogen alleviates microgravity-induced bone loss in rats. Molecular
      hydrogen could thus be envisaged as a nutritional countermeasure for spaceflight
      but remains to be tested in humans.

PMID- 22648001
TI  - Intact fibroblast growth factor 23 and fragments in plasma from Gambian children.
AB  - Fibroblast growth factor 23 (FGF23) is grossly elevated in Gambian children with
      rickets and, at a lower prevalence, in those without bone deformities. We used
      western blotting to mimic the detection capabilities of the C-terminal FGF23
      enzyme-linked immunosorbent assay (ELISA). Only intact FGF23 hormone was present
      in Gambian plasma samples from children with and without rickets. INTRODUCTION:
      Elevated circulating FGF23 concentrations have been detected in plasma samples
      from Gambian children using the C-terminal Immutopics ELISA. The Immutopics ELISA
      detects both the intact FGF23 hormone and the C-terminal fragment. The aim of
      this study was to determine whether the elevated FGF23 concentrations as detected
      by the ELISA were predominantly due to a high proportion of intact FGF23 hormone
      and/or C-terminal FGF23 fragments. METHODS: Stored, frozen plasma samples from
      previous studies of Gambian children with known concentrations of FGF23 as
      determined by C-terminal Immutopics ELISA assay, were selected for western
      blotting analysis: from children with rickets-like bone deformities (n = 4) and
      local controls (n = 4), with elevated >900 RU/ml (n = 2) and normal <30 RU/ml (n
      = 2; from each group). The anti-FGF23 polyclonal antibody that recognizes the C
      terminal of FGF23 (as used in the Immutopics kit) was used as the primary
      antibody and the anti-IgG polyclonal antibody conjugated to horseradish
      peroxidase (HRP) was used as the secondary antibody. RESULTS: Firstly, C-terminal
      FGF23 fragments, although detectable in standards from the Immutopics ELISA kit,
      were not in the Gambian plasma samples. Secondly, there was no difference in the
      size of FGF23 molecules present in plasma from children with rickets-like bone
      deformities and children from the local community. CONCLUSIONS: Western blotting
      has provided evidence that elevated FGF23 concentrations, as determined by the C
      terminal Immutopics ELISA, measured in Gambian children with and without rickets
      like bone deformities was not caused by an increased proportion of circulating
      inactive C-terminal fragments.

PMID- 22648002
TI  - Understanding the molecular basis of MK2-p38alpha signaling complex assembly:
      insights into protein-protein interaction by molecular dynamics and free energy
      studies.
AB  - The formation of a p38 MAPK and MAPK-activated protein kinase 2 (MK2) signaling
      complex is physiologically relevant to cellular responses such as the
      proinflammatory cytokine production. The interaction between p38alpha isoform and
      MK2 is of great importance for this signaling. In this study, molecular dynamics
      simulation and binding free energy calculation were performed on the MK2-p38alpha
      signaling complex to investigate the protein-protein interaction between the two
      proteins. Dynamic domain motion analyses were performed to analyze the
      conformational changes between the unbound and bound states of proteins during
      the interaction. The activation loop, alphaF-I helices, and loops among alpha
      helices in the C-lobe of MK2 are found to be highly flexible and exhibit
      significant changes upon p38alpha binding. The results also show that after the
      binding of p38alpha, the N- and C-terminal domains of MK2 display an opening and
      twisting motion centered on the activation loop. The molecular mechanics Poisson
      Boltzmann and generalized-Born surface area (MM-PB/GBSA) methods were used to
      calculate binding free energies between MK2 and p38alpha. The analysis of the
      components of binding free energy calculation indicates that the van der Waals
      interaction and the nonpolar solvation energy provide the driving force for the
      binding process, while the electrostatic interaction contributes critically to
      the specificity, rather than to MK2-p38alpha binding affinity. The contribution
      of each residue at the interaction interface to the binding affinity of MK2 with
      p38alpha was also analyzed by free energy decomposition. Several important
      residues responsible for the protein-protein interaction were also identified.

PMID- 22648003
TI  - On the microscopic origin of bending of graphene nanoribbons in the presence of a
      perpendicular electric field.
AB  - Herein, we predict that graphene nanoribbons will be nonplanar under the
      influence of a critical perpendicular field. Our investigation demonstrates that
      the perpendicular field induces mixing of sigma and pi orbitals in graphene
      nanoribbons through the second order Stark effect which eventually modulates the
      electron-nuclear interaction strongly in favor of a bent structure.

PMID- 22648004
TI  - CD14 polymorphisms correlate with an augmented risk for celiac disease in Italian
      patients.
AB  - Celiac disease (CD) is a T-cell-mediated chronic inflammatory disease
      characterized by autoimmune, immunological and environmental components, where
      genetic factors in addition to the main known risk factors (gliadin and human
      leukocyte antigen (HLA)-DQ haplotypes) are supposed to be involved. CD14 is a
      multifunctional receptor involved in the bacterial lipopolysaccharides-dependent
      signal transduction. The CD14 gene maps on the long arm of chromosome 5 (5q22
      q32), a 'hotbed' region for CD; promoter polymorphisms are known to influence its
      expression. In this study we analyzed three CD14 promoter polymorphisms (c.
      1359G>T, c.-1145A>G and c.-159C>T, ) in 938 CD Italian patients and 533 healthy
      controls, with known HLA-DQ haplotypes, with the aim of evaluating their possible
      association with the disease. The c.-1145A>G G and c.-159C>T T alleles (as well
      as the combination of the two alleles in the GT haplotype), were identified as
      susceptibility factors for CD development, being significantly more frequent in
      CD patients than in healthy controls. This association was also confirmed when
      the analysis was restricted to only those subjects characterized by HLA-DQ risk
      haplotypes. Our results indicate the involvement of CD14 gene polymorphisms in
      the susceptibility to CD.

PMID- 22648005
TI  - Effect of a high-fructose diet on glucose tolerance, plasma lipid and
      hemorheological parameters during oral contraceptive administration in female
      rats.
AB  - Oral contraceptive (OC) use and increased fructose feeding have been associated
      with altered cardiometabolic effects. The effect of increased dietary fructose
      during OC use on cardiometabolic parameters is unknown. We investigated the
      effects of a high-fructose diet on body weight gain, fasting blood glucose,
      glucose tolerance, plasma lipid and hemorheological parameters in female rats
      treated with a combination of OC steroids (norgestrel/ethinyl estradiol; NEE).
      Rats were given (p.o.) vehicle, high-dose NEE (10.0 MUg norgestrel/1.0 MUg
      ethinyl estradiol) or low-dose NEE (1.0 MUg norgestrel/0.1 MUg ethinyl estradiol)
      with or without high dietary fructose daily for 6 weeks. Results demonstrated
      that high-dose NEE but not low-dose NEE treatment led to significant increases in
      hematocrit, blood viscosity, and decreases in body weight gain, glucose
      tolerance, and plasma HDL-cholesterol level. Both NEE treatments resulted in
      significant increases in plasma viscosity and triglyceride. Increased dietary
      fructose without NEE treatment produced significant increases in fasting blood
      glucose, hematocrit, blood and plasma viscosities, while increased dietary
      fructose significantly potentiated the effects on blood and plasma viscosities
      observed during NEE treatment. Conversely, the effects of NEE treatment on body
      weight gain, glucose tolerance, plasma triglyceride and HDL-cholesterol were
      significantly attenuated. In conclusion, the results indicate that increase in
      dietary fructose may worsen abnormal blood rheology. The results also demonstrate
      that increased dietary fructose may not impact negatively on glucose and lipid
      metabolisms during OC use. The findings imply that fructose-enriched diet might
      be an important consideration during OC use regarding blood rheological
      properties.

PMID- 22648006
TI  - Aberrant somatosensory perception in Anorexia Nervosa.
AB  - Anorexia Nervosa (AN) patients have a disturbed experience of body size and
      shape. Previously it has been shown that these body representation disturbances
      extend to enlarged perception of tactile distances. Here we investigated whether
      misperception of tactile size could be related to inaccurate elementary
      somatosensory perception. Tactile size perception was measured with the Tactile
      Estimation Task (TET) (see Keizer et al., 2011). Elementary somatosensory
      perception was assessed with a pressure detection task and two point
      discrimination (TPD). Compared to controls (n=28), AN patients (n=25)
      overestimated tactile size, this effect was strongest for the abdomen. Elementary
      tactile perception deviated in AN as well: Patients had a lower threshold for
      detecting pressure on their abdomen, and a higher threshold for TPD on both the
      arm and abdomen. Regression results implied that group membership predicted
      tactile size estimation on the arm. Both group membership and TPD predicted
      tactile size estimation on the abdomen. Our results show that AN patients have a
      disturbance in the metric properties of the mental representation of their body
      as they overestimate the size of tactile stimuli compared to controls.
      Interestingly, AN patients and controls differ in elementary somatosensory
      perception as well. However, this could not solely explain misperception of
      tactile distances, suggesting that both bottom-up and top-down processes are
      involved.

PMID- 22648007
TI  - Antisaccades as a follow-up tool in major depressive disorder therapies: a pilot
      study.
AB  - Eight patients with major depression, included in a double-blind study, performed
      an antisaccade task. Results suggested a link between antisaccade performances
      and clinical scale scores in patients who respond to therapy. Moreover, error
      rates may well predict response from day of inclusion, thus serving as a state
      marker for mood disorders.

PMID- 22648008
TI  - Attention-deficit hyperactivity disorder in chronic fatigue syndrome patients.
AB  - Psychopathological disorders are frequent in chronic fatigue syndrome patients.
      The present study examines the presence of attention-deficit hyperactivity
      disorder (ADHD) in a sample of adult chronic fatigue syndrome (CFS) patients, and
      evaluates its clinical consequences in this population. CFS patients were
      assessed for childhood and adult ADHD by clinical interview and ADHD-specific
      scales. Psychopathological comorbidities were evaluated by clinical examination
      and questionnaires. Forty-seven of 158 CSF patients (29.7%) were diagnosed of
      childhood ADHD and in 33 (20.9%), the condition persisted into adulthood. CFS
      patients with adult ADHD had an earlier CSF onset, more severe anxiety and
      depression symptoms, and a higher risk of suicide than CFS patients without ADHD.
      Using lineal regression analysis, we found that depressive symptoms and ADHD
      severity were significant predictors of fatigue intensity. Consequently, ADHD may
      be common in CFS patients, and is associated with a more severe psychopathologic
      clinical profile.

PMID- 22648009
TI  - The New York PTSD risk score for assessment of psychological trauma: male and
      female versions.
AB  - We previously developed a new posttraumatic stress disorder (PTSD) screening
      instrument-the New York PTSD Risk Score (NYPRS). Since research suggests
      different PTSD risk factors and outcomes for men and women, in the current study
      we assessed the suitability of male and female versions of this screening
      instrument among 3298 adults exposed to traumatic events. Using diagnostic test
      methods, including receiver operating characteristic (ROC) curve and bootstrap
      techniques, we examined different prediction domains, including core PTSD
      symptoms, trauma exposures, sleep disturbances, depression symptoms, and other
      measures to assess PTSD prediction models for men and women. While the original
      NYPRS worked well in predicting PTSD, significant interaction was detected by
      gender, suggesting that separate models are warranted for men and women. Model
      comparisons suggested that while the overall results appeared robust, prediction
      results differed by gender. For example, for women, core PTSD symptoms
      contributed more to the prediction score than for men. For men, depression
      symptoms, sleep disturbance, and trauma exposure contributed more to the
      prediction score. Men also had higher cut-off scores for PTSD compared to women.
      There were other gender-specific differences as well. The NYPRS is a screener
      that appears to be effective in predicting PTSD status among at-risk populations.
      However, consistent with other medical research, this instrument appears to
      require male and female versions to be the most effective.

PMID- 22648010
TI  - Catecholamine-related gene expression in blood correlates with tic severity in
      tourette syndrome.
AB  - Tourette syndrome (TS) is a heritable disorder characterized by tics that are
      decreased in some patients by treatment with alpha adrenergic agonists and
      dopamine receptor blockers. Thus, this study examines the relationship between
      catecholamine gene expression in blood and tic severity. TS diagnosis was
      confirmed using Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV
      criteria and tic severity measured using the Yale Global Tic Severity Scale
      (YGTSS) for 26 un-medicated subjects with TS. Whole blood was collected and
      Ribonucleic acid (RNA) processed on Affymetrix Human Exon 1.0 ST arrays. An
      Analysis of Covariance (ANCOVA) identified 3627 genes correlated with tic
      severity (p<0.05). Searches of Medical Subject Headings, Gene Ontology, Allen
      Mouse Brain Atlas, and PubMed determined genes associated with catecholamines and
      located in the basal ganglia. Using GeneCards, PubMed, and manual curation, seven
      genes associated with TS were further examined: DRD2, HRH3, MAOB, BDNF, SNAP25,
      SLC6A4, and SLC22A3. These genes are highly associated with TS and have also been
      implicated in other movement disorders, Attention Deficit Hyperactivity Disorder
      (ADHD), and Obsessive-Compulsive Disorder (OCD). Correlation of gene expression
      in peripheral blood with tic severity may allow inferences about catecholamine
      pathway dysfunction in TS subjects. Findings built on previous work suggest that
      at least some genes expressed peripherally are relevant for central nervous
      system (CNS) pathology in the brain of individuals with TS.

PMID- 22648012
TI  - Transfer hydrogenation with a ferrocene diamide ruthenium complex.
AB  - The use of a 1,1'-ferrocenediamide ruthenium complex as a mediator for base-free
      transfer hydrogenation is reported. Ketones were transformed to their respective
      alcohols at room temperature in 36-99% conversions with turnover frequencies up
      to 339 h(-1).

PMID- 22648011
TI  - Selective neurocognitive deficits and poor life functioning are associated with
      significant depressive symptoms in alcoholism-HIV infection comorbidity.
AB  - Alcoholism, HIV, and depressive symptoms frequently co-occur and are associated
      with impairment in cognition and life function. We administered the Beck
      Depression Inventory-II (BDI-II), measures of life function, and neurocognitive
      tests to 67 alcoholics, 56 HIV+ patients, 63 HIV+ alcoholics, and 64 controls to
      examine whether current depressive symptom level (significant, BDI-II>14 vs.
      minimal, BDI-II<14) was associated with poorer cognitive or psychosocial function
      in alcoholism-HIV comorbidity. Participants with significant depressive symptoms
      demonstrated slower manual motor speed and poorer visuospatial memory than those
      with minimal depressive symptoms. HIV patients with depressive symptoms showed
      impaired manual motor speed. Alcoholics with depressive symptoms showed impaired
      visuospatial memory. HIV+ alcoholics with depressive symptoms reported the
      poorest quality of life; alcoholics with depressive symptoms, irrespective of HIV
      status, had poorest life functioning. Thus, significant depressive symptoms were
      associated with poorer selective cognitive and life functioning in alcoholism and
      in HIV infection, even though depressive symptoms had neither synergistic nor
      additive effects on cognition in alcoholism-HIV comorbidity. The results suggest
      the relevance of assessing and treating current depressive symptoms to reduce
      cognitive compromise and functional disability in HIV infection, alcoholism, and
      their comorbidity.

PMID- 22648013
TI  - Infection control practices in facilities for highly infectious diseases across
      Europe.
AB  - BACKGROUND: The management of patients with highly infectious diseases (HIDs) is
      a challenge for healthcare provision requiring a high level of care without
      compromising the safety of other patients and healthcare workers. AIM: To study
      the infection control practice in isolation facilities participating in the
      European Network for Highly Infectious Diseases (EuroNHID) project. METHODS: A
      survey was conducted during 2009 of 48 isolation facilities caring for patients
      with HIDs in 16 European countries. Checklists and standard evaluation forms were
      used to collect and interpret data on hand hygiene, routine hygiene and
      disinfection, and waste management. FINDINGS: Forty percent of HIDs had no non
      hand-operated sinks or alcohol-based antiseptic distributors, while 27% did not
      have procedures for routine hygiene, final disinfection, or safe discarding of
      non-disposable objects or equipment. There was considerable variation in the
      management of waste and in the training of housekeeping personnel. EuroNHID has
      developed recommendations for hand hygiene, disinfection, routine hygiene, and
      waste management. CONCLUSIONS: Most aspects of hand hygiene, routine hygiene and
      disinfection, and waste management were considered at least partially adequate in
      the majority of European isolation facilities dedicated for the care of patients
      with HIDs. But considerable variability was observed, with management of waste
      and training of housekeeping personnel being generally less satisfactory.

PMID- 22648014
TI  - Comparative analysis of the variable 3' UTR and gene expression of the KIN and
      KIN-homologous LEA genes in Capsella bursa-pastoris.
AB  - As the crucial members of the cold-regulated (COR) gene family, KIN genes are
      involved in diverse abiotic stress responses in plants. In the present study, KIN
      genes from the widespread plant Capsella bursa-pastoris were identified and
      analyzed to better understand the powerful adaptation of this species. Two KIN
      genes were cloned and sequenced by 3' RACE. As some COR genes are homologous to
      LEA genes, three KIN-homologous LEA genes were also identified. We deduced the
      amino acid sequences of the five proteins to estimate their phylogenetic
      relationships, and grouped them into three subfamilies (CI, CII, and CIII).
      Variable 3' UTRs were found in CI, CII, and CIII genes. Using qPCR, we evaluated
      the transcriptional levels of the five genes in different organs and embryonic
      stages. Two CI genes were exclusively expressed in early embryos and flowers. The
      CII and CIII genes showed obvious up-regulation in young leaves after heat
      stress, cold stress, and ABA treatment. Two of the CI genes, however, rarely
      responded to those stresses in young leaves. In contrast, all five genes showed
      differential responses in flowers when C. bursa-pastoris plants were sprayed with
      ABA. Furthermore, the expression of these genes in C. bursa-pastoris was compared
      to that of the corresponding Arabidopsis genes, and similar gene expression
      profiles were found in both species. Our findings suggest that these five genes
      play different roles in development and the responses to abiotic stresses in C.
      bursa-pastoris. Key message We characterized two KIN and three KIN-homologous LEA
      genes, and analyzed their variable 3'UTR and organ-specific, embryo
      developmental, stress-induced gene expression in Capsella bursa-pastoris.

PMID- 22648016
TI  - Orthogonal plating of intra-articular distal radius fractures with an associated
      radial column fracture via a single volar approach.
AB  - INTRODUCTION: The purpose of this study was to investigate the radiographic and
      functional outcome of orthogonal plating (two plates at right angles) via a
      single volar approach for fixation of intra-articular distal radius fractures
      with an associated radial column fracture. METHODS: In a retrospective, chart
      based review, we identified 14 consecutive patients with an intra-articular
      distal radial fracture who had been treated with locked volar plate fixation and
      an additional radial column plate. Radial column plates were LCP Distal Radius
      Plates 2.4; volar plates were LCP Distal Radius Plates 2.4 (n=13) or LCP T-plate
      (n=1). These patients were operated on using the extended volar flexor carpi
      radialis (FCR) approach as described by Orbay. Radiographic measurements, healing
      rates, time to union, complications, range of motion, the Gartland and Werley
      score, and the QuickDASH questionnaire were done in order to evaluate the
      radiographic and functional outcomes of this technique. RESULTS: Thirteen of the
      14 fractures healed within 7 weeks after surgery. Two implant removals were done.
      One patient had malposition of the fracture and carpal tunnel symptoms, which
      required a second surgery. No other complications (e.g., first dorsal compartment
      problems, radial plate prominence problems and radial sensory nerve problems)
      were observed. The average length of follow-up was 30 months (range, 12.8 months
      to 5.4 years). Radiographic results after healing were radial inclination 20
      degrees , radial length 11.4mm, tilt 6 degrees  volar, ulnar variance -0.5mm,
      articular gap 0.1mm and step-off 0.1mm. Wrist range of motion was flexion
      extension arc 93 degrees , ulnar-radial deviation arc 49 degrees  and pronation
      supination arc 152 degrees . Nine patients scored 'excellent' on the Gartland and
      Werley score, while the remaining five patients scored 'good'. The average
      QuickDASH score was 13.4. CONCLUSION: Additional fixation of a radial column
      process in an intra-articular distal radius fracture via the extended FCR
      approach using a standard volar plate and radial LCP resulted in good/excellent
      radiographic and functional outcome. LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22648015
TI  - The changing epidemiology of spinal trauma: a 13-year review from a Level I
      trauma centre.
AB  - INTRODUCTION: Spinal injuries secondary to trauma are a major cause of patient
      morbidity and a source of significant health care expenditure. Increases in
      traffic safety standards and improved health care resources may have changed the
      characteristics and incidence of spinal injury. The purpose of this study was to
      review a single metropolitan Level I trauma centre's experience to assess the
      changing characteristics and incidence of traumatic spinal injuries and spinal
      cord injuries (SCI) over a 13-year period. PATIENTS AND METHODS: A retrospective
      review of patients admitted to a Level I trauma centre between 1996 and 2008 was
      performed. Patients with spinal fractures and SCI were identified. Demographics,
      mechanism of injury, level of spinal injury and Injury Severity Score (ISS) were
      extracted. The outcomes assessed were the incidence rate of SCI and in-hospital
      mortality. RESULTS: Over the 13-year period, 5.8% of all trauma patients suffered
      spinal fractures, with 21.7% of patients with spinal injuries having SCI. Motor
      vehicle accidents (MVAs) were responsible for the majority of spinal injuries
      (32.6%). The mortality rate due to spinal injury decreased significantly over the
      study period despite a constant mean ISS. The incidence rate of SCI also
      decreased over the years, which was paralleled by a significant reduction in MVA
      associated SCI (from 23.5% in 1996 to 14.3% in 2001 to 6.7% in 2008). With
      increasing age there was an increase in spinal injuries; frequency of blunt SCI;
      and injuries at multiple spinal levels. CONCLUSION: This study demonstrated a
      reduction in mortality attributable to spinal injury. There has been a marked
      reduction in SCI due to MVAs, which may be related to improvements in motor
      vehicle safety and traffic regulations. The elderly population was more likely to
      suffer SCI, especially by blunt injury, and at multiple levels. Underlying
      reasons may be anatomical, physiological or mechanism related.

PMID- 22648017
TI  - Rapid response teams and failure to rescue: one community's experience.
AB  - The rapid response team has been proposed as an effective strategy for reducing
      failure-to-rescue rates among adult inpatients; however, there is little research
      evidence to support the recommendation. This exploratory study used survey and
      administrative data to describe rapid response team characteristics and
      penetration among hospitals in a large metropolitan area while tracking
      corresponding failure-to-rescue rates among surgical inpatients over 5 years. The
      findings are promising and invite further investigation.

PMID- 22648018
TI  - Burkholderia gladioli sepsis in newborns.
AB  - Burkholderia gladioli is a rare cause of bacteremia and sepsis in the absence of
      such predisposing factors as chronic granulomatous disease, cystic fibrosis, and
      immunosuppression. Little is known about B. gladioli infection in newborns. The
      aim of this study was to present the features of B. gladioli infection in
      newborns. Clinicopathological characteristics, patterns of antimicrobial
      susceptibility, predisposing factors, and outcomes of B. gladioli bloodstream
      infection were retrospectively analyzed in newborns treated between 2008 and
      2011. During the 3-year study period, B. gladioli was isolated from the blood
      cultures of 14 patients (3.7 per 1,000 admissions). In all, 5 (35.7 %) of the 14
      cases had a positive blood culture at the time of initial admission. Primary
      diagnoses in the neonates were severe major congenital anomalies, congenital
      leukemia, prematurity with respiratory distress syndrome, pneumonia, and
      parapneumonic pleural effusion. In total, 10 (71.4 %) of the patients underwent
      >=2 invasive procedures. The overall in-hospital mortality rate was 21.4 %,
      whereas the mortality rate due to B. gladioli infection was 7 %. CONCLUSION: B.
      gladioli might be a causative microorganism of both early neonatal and nosocomial
      sepsis in newborns. To the best of our knowledge, this is the first study on B.
      gladioli infection in newborns. Invasive procedures and severe major congenital
      anomalies may be predisposing factors for B. gladioli bloodstream infection in
      neonates. Although it appears to have low pathogenic potential and an insidious
      clinical course in newborns, resistance to antibiotics may be a potential
      problem. Mortality was primarily associated with underlying diseases.

PMID- 22648019
TI  - Clinicopathological features in the recurrence of oligodendroglioma and diffuse
      astrocytoma.
AB  - To investigate whether grade II oligodendroglioma was transformed to glioblastoma
      or not, histopathological evaluation of recurrent oligodendrogliomal tumors (OG)
      and diffuse astrocytomas (DA) was performed. The OG group was composed of ten
      patients with OG, including seven oligodendrogliomas and three oligoastrocytomas.
      The DA group was composed of ten patients with DA, including eight fibrillary
      astrocytomas and two gemistocytic astrocytomas. The histopathological parameters
      of glioblastoma including nuclear atypia, multinucleated giant cells, glomeruloid
      tufts (GT) as a marker of microvascular proliferation, necrosis, and the Ki-67
      staining index were investigated. Evaluation of these parameters was scored as
      follows: 0, none; 1, sporadic; 2, partial; 3, extensive. There were no cases of
      transformation to glioblastoma in the OG group. There were five cases of
      transformation to secondary glioblastoma in the DA group. In recurrent tumors,
      scores of GT and necrosis in the OG group were significantly lower than those in
      the DA group (p < 0.005). Nuclear atypia and high proliferative activity (Ki-67
      index) were identified in recurrent tumors of the OG group. Our study suggested
      that the extent of GT and necrosis in recurrent OG was less than that in
      recurrent DA, and transformation to glioblastoma from oligodendroglial tumor was
      exceptional.

PMID- 22648020
TI  - Seed bank of Cu-contaminated topsoils at a wood preservation site: impacts of
      copper and compost on seed germination.
AB  - Is identification of seed bank (SB) species useful for sustainable management of
      vegetation restoration on Cu-contaminated soils? How does Cu contamination of the
      soil affect the SB and can incorporating compost into Cu-contaminated soils
      counter the effects of Cu? The topsoil SB was investigated at seven contaminated
      sub-sites of a wood preservation site. The germination parameters of the seeds
      were recorded using three substrates: a washed river sand (Sand), the same sand
      spiked with CuSO(4) to reach the same Cu concentrations as in the soil pore water
      (0.3 to 3.2 mg Cu/L) (Cu), and the same Cu-spiked sand amended with compost
      (CPM). The total number of germinated seeds (NGS) was 1,081. The whole seedling
      dataset enabled 12 plant species and eight families to be identified in the SB.
      Species richness and Shannon indexes were low. The addition of Cu in the
      germination substrate enhanced total NGS at one sub-site and the addition of CPM
      increased plant diversity at three sub-sites. SB composition varied with the sub
      site but did not correlate with total soil Cu or with the Cu concentration in the
      soil pore water. Three species belonging to the Poaceae family dominated. In
      terms of total NGS, the dominant species were Portulaca oleracea and Agrostis
      capillaris. Similarities between SB and established vegetation were low but
      increased when the soil bulk density was reduced. The Cu-tolerant species P.
      oleracea and A. capillaris dominated in both the SB and the established
      vegetation. However, the pattern of SB and established vegetation differed and
      consequently SB was not a sufficient indicator to predict the future vegetation.

PMID- 22648021
TI  - Persistence of insecticides in ready-mix formulations and their efficacy against
      Lipaphis erysimi (Kalt) in cauliflower.
AB  - Persistence of cypermethrin, deltamethrin, profenofos, and triazophos in
      cauliflower curd was studied, following application of two premix formulations
      viz: Roket 44EC (profenofos 40 % + cypermethrin 4 %) and Anaconda Plus 36EC
      (triazophos 35 % + deltamethrin 1 %) at recommended (1.0 L ha(-1)) and double
      doses (2.0 L ha(-1)). In the case of Roket 44EC, residues of cypermethrin
      dissipated with the half-life values of 1.5-2.1 days, whereas residues of
      profenofos dissipated with the half-life of 2.9-3.3 days on cauliflower curd. In
      the case of Anaconda, residues of triazophos and deltamethrin dissipated from
      curd with the half-life values of 2.6-3.0 and 2.2-2.6 days, respectively. Both
      the combination mix significantly reduced the aphid population up to 14 days
      after spray and increased the yield by 155-160 % over control. Anaconda (2.0 L
      ha(-1)) treated plots yielded the highest number of marketable curds. Based on
      risk assessment analysis, safe waiting period of 3 and 5 days has been suggested
      for Roket 44EC and Anaconda Plus 36EC, respectively, in cauliflower at
      recommended dose of application.

PMID- 22648023
TI  - A methodological systematic review on surgical site infections following spinal
      surgery: part 2:  prophylactic treatments.
AB  - STUDY DESIGN: A methodological systematic review. OBJECTIVE: To critically
      appraise the validity of preventive effects attributed to prophylactic treatments
      for surgical site infection (SSI) after spinal surgery. SUMMARY OF BACKGROUND
      DATA: As a result of a rapidly increasing number of spinal procedures, health
      care expenditure is expected to increase substantially in the foreseeable future.
      Administration of effective prophylactic treatments may prevent occurrence of
      SSIs and may thus result in lower costs. To date, however, no review appraising
      the methodological quality of studies evaluating prophylactic treatments for
      spinal SSIs has been published. METHODS: Contemporary studies evaluating the
      preventive effect of prophylactic interventions on the rate of SSI after spinal
      surgery were searched through the Medline and EMBASE databases (January 2001 to
      December 2010). References were retrieved and bias-prone study features were
      abstracted individually and independently by 2 authors. RESULTS: Eighteen
      eligible studies were identified, including 6 randomized controlled trials and 12
      comparative cohort studies. Most often, antibiotic prophylaxis administration was
      investigated (n = 7). Included studies covered a wide variation of indications
      and surgical procedures. Except for 5 studies (28%), applied definitions of SSI
      outcomes were ambiguous. Although several important methodological aspects,
      including blinding of outcome assessors and attrition, were poorly reported in
      randomized controlled trials, these studies were far less susceptible to bias and
      confounding as observed in nonrandomized studies. None of the 12 cohort studies
      adjusted for confounding by matching, stratification, or multivariate regression
      techniques. CONCLUSION: Given the plethora of previously hypothesized confounding
      risk factors for a spinal SSI, conduct of nonrandomized comparative therapeutic
      studies is strongly discouraged. On the other hand, methodological safeguards,
      including use of standardized definitions of putative confounders and outcomes,
      should be considered in more detail during the design phase of a randomized
      trial.

PMID- 22648024
TI  - Intervertebral disc height changes after weight reduction in morbidly obese
      patients and its effect on quality of life and radicular and low back pain.
AB  - STUDY DESIGN: Prospective study in a morbidly obese population after bariatric
      surgery. OBJECTIVE: To document the effect of significant weight reduction on
      intervertebral disc space height, axial back pain, radicular leg pain, and
      quality of life. SUMMARY OF BACKGROUND DATA: Low back pain is a common complaint
      in obese patients, and weight loss is found to improve low back pain and quality
      of life. The mechanism by which obesity causes low back pain is not fully
      understood. On acute axial loading and offloading, intervertebral disc changes
      its height; there are no data on intervertebral disc height changes after
      significant weight reduction. METHODS: Thirty morbidly obese adults who underwent
      bariatric surgery for weight reduction were enrolled in the study. Disc space
      height was measured before and 1 year after surgery. Visual analogue scale was
      used to evaluate axial and radicular pain. The 36-Item Short Form Health Survey
      and Moorehead-Ardelt questionnaires were used to evaluate changes in quality of
      life. RESULTS: Body weight decreased at 1 year after surgery from an average of
      119.6 +/- 20.7 kg to 82.9 +/- 14.0 kg corresponding to an average reduction in
      body mass index of 42.8 +/- 4.8 kg/m(2) to 29.7 +/- 3.4 kg/m(2) (P < 0.001). The
      L4-L5 disc space height increased from 6 +/- 1.3 mm, presurgery to 8 +/- 1.5 mm 1
      year postsurgery (P < 0.001). Both axial and radicular back pain decreased
      markedly after surgery (P < 0.001). Patients' Moorehead-Ardelt score
      significantly improved after surgery (P < 0.001). Although the 36-Item Short Form
      Health Survey score did not show any statistically significant improvement after
      surgery, the physical component of the questionnaire showed a positive trend for
      improvement. No correlation was noted between the amount of weight reduction and
      the increment in disc space height or back pain improvement. CONCLUSION:
      Bariatric surgery, resulting in significant weight reduction, was associated with
      a significant decrease in low back and radicular pain as well as a marked
      increase in the L4-L5 intervertebral disc height. Reduction in body weight after
      bariatric surgery in morbidly obese patients is associated with a significant
      radiographical increase in the L4-L5 disc space height as well as a significant
      clinical improvement in axial back and radicular leg pain.

PMID- 22648025
TI  - Morphological features and clinical significance of epidural membrane in the
      cervical spine.
AB  - STUDY DESIGN: A prospective clinical study. OBJECTIVE: To elucidate the
      histomorphological features and clinical significance of the epidural membrane
      (EM) in the cervical spine based on operative and histological findings. SUMMARY
      OF BACKGROUND DATA: The anatomical features of the EM have been mostly discussed
      on the basis of cadaver studies in the whole spine. However, the
      histomorphological features and clinical significance of the EM in the cervical
      spine based on operative findings have never been reported. METHODS: Eighty-seven
      patients with cervical spondylotic myelopathy who had undergone an expansive open
      door laminoplasty under microscopy were evaluated with a more than 2-year follow
      up period. The most damaged spinal segment was determined in each patient from
      the preoperative neurological and image findings along with the remaining
      symptoms at follow-up. The morphological features of the EM were observed and
      recorded in each patient during decompression. For histology, specimens of common
      and remarkable types of the EM obtained from 16 patients were examined. RESULTS:
      The age at surgery averaged 64.5 years; there were 58 men and 29 women. With
      regard to the most damaged spinal segment, there were 14 cases at the C3-C4
      level, 37 at the C4-C5 level, 32 at the C5-C6 level, and 4 at the C6-C7 level.
      The EM was an adipo-fibro-vascular tissue with various histomorphologies,
      blending with the periradicular sheath. Some EMs showed notable findings:
      obstructing dural tube expansion (13 cases, 14.9%), compressing a nerve root or
      disturbing its mobility (4 cases, 4.6%), and the combined type (1 case, 1.1%).
      All of them were located at approximately the most damaged spinal segment. In
      addition, some EMs had interesting histological features, such as harboring many
      small arteries, calcified debris, and metaplastic bone fragments. CONCLUSION: The
      EM can develop into remarkable structures with spondylosis and aging in patients
      with cervical spondylotic myelopathy, affecting surgical outcomes as well as
      successful decompression procedures. A sound understanding of the
      histomorphological features of the EM is required to obtain satisfactory surgical
      outcomes in the limited field afforded by minimally invasive surgery.

PMID- 22648026
TI  - The position of the aorta changes with altered body position in single right
      thoracic adolescent idiopathic scoliosis: a magnetic resonance imaging study.
AB  - STUDY DESIGN: A prospective clinical magnetic resonance imaging study. OBJECTIVE:
      To explore the differences in the position of the aorta relative to the spine in
      patients with single right thoracic adolescent idiopathic scoliosis (RT-AIS) in 2
      different body positions (supine and prone). SUMMARY OF BACKGROUND DATA: Pedicle
      screws are used widely in scoliosis surgery. With an increase in the incidence of
      vascular complications that result from misplaced pedicle screws, studies
      regarding the spatial relationship of the aorta and the vertebral body have also
      gradually increased and show that the aorta is positioned more posteriorly in
      patients with RT-AIS than in normal subjects. In these imaging studies, the
      patients received computed tomographic or magnetic resonance (MR) scans in the
      supine position. Recent studies of subjects without a spinal deformity found that
      the aorta moves from a posterolateral to an anteromedial position when the
      subject changes from a supine position to a prone position. However, no studies
      investigated aorta shifting with changing body position in patients with AIS.
      METHODS: Twenty-six patients with single RT-AIS were recruited into this study.
      Each patient received an axial MR scan from T5 through L3 in both the supine and
      prone positions. In the Cartesian coordinate system, the left pedicle-aorta (LtP
      Ao) angle, LtP-Ao distance, and vertebral rotation angle were measured from T5
      through L3 in the axial plane MR images. We also simulated misplacement of the
      pedicle screw with commonly used length and 20 degrees  direction error, and the
      potential risk of aorta impingement was defined as the virtual pedicle screw
      crossing the aorta. The paired sample t test was used to compare these parameters
      between the 2 body positions. RESULTS: The mean LtP-Ao angle and mean LtP-Ao
      distance differed between the body positions at each level. At the T5-T10 levels,
      the patients in the prone position exhibited significantly smaller LtP-Ao angles
      (26.2 degrees  vs. 38.8 degrees ; P, 0.01) and distances (27.0 vs. 30.7 mm; P,
      0.01) than those in the supine position. The vertebral rotation angle was larger
      in the prone position than in the supine position at periapical levels, although
      this difference did not reach statistical significance (P . 0.05). The percentage
      of potential risk of aorta impingement was significantly higher in the prone
      position than in the supine position at the T5-T10 levels (19.7% vs. 6.6%,
      respectively; P, 0.05). CONCLUSION.: The aorta shifts more anteromedially and
      more closely to the spine at the T5-T10 levels when patients with RT-AIS change
      from the supine to the prone position. Thus, in the prone position, the aorta is
      potentially at a higher risk for injury from anterior and lateral cortex
      penetration by the left pedicle screws. The spinal surgeon should be aware of
      these altered conditions to avoid injury to the aorta during pedicle screw
      insertion in patients with RT-AIS who are in the prone position.

PMID- 22648027
TI  - The retrograde delivery of adenovirus vector carrying the gene for brain-derived
      neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the
      chronically compressed spinal cord of twy/twy mice.
AB  - STUDY DESIGN: The twy/twy mouse undergoes spontaneous chronic mechanical
      compression of the spinal cord; this in vivo model system was used to examine the
      effects of retrograde adenovirus (adenoviral vector [AdV])-mediated brain-derived
      neurotrophic factor (BDNF) gene delivery to spinal neural cells. OBJECTIVE: To
      investigate the targeting and potential neuroprotective effect of retrograde AdV
      mediated BDNF gene transfection in the chronically compressed spinal cord in
      terms of prevention of apoptosis of neurons and oligodendrocytes. SUMMARY OF
      BACKGROUND DATA: Several studies have investigated the neuroprotective effects of
      neurotrophins, including BDNF, in spinal cord injury. However, no report has
      described the effects of retrograde neurotrophic factor gene delivery in
      compressed spinal cords, including gene targeting and the potential to prevent
      neural cell apoptosis. METHODS: AdV-BDNF or AdV-LacZ (as a control gene) was
      injected into the bilateral sternomastoid muscles of 18-week old twy/twy mice for
      retrograde gene delivery via the spinal accessory motor neurons. Heterozygous
      Institute of Cancer Research mice (+/twy), which do not undergo spontaneous
      spinal compression, were used as a control for the effects of such compression on
      gene delivery. The localization and cell specificity of beta-galactosidase
      expression (produced by LacZ gene transfection) and BDNF expression in the spinal
      cord were examined by coimmunofluorescence staining for neural cell markers
      (NeuN, neurons; reactive immunology protein, oligodendrocytes; glial fibrillary
      acidic protein, astrocytes; OX-42, microglia) 4 weeks after gene injection. The
      possible neuroprotection afforded by retrograde AdV-BDNF gene delivery versus AdV
      LacZ-transfected control mice was assessed by scoring the prevalence of apoptotic
      cells (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end
      labeling-positive cells) and immunoreactivity to active caspases -3, -8, and -9,
      p75, neurofilament 200 kD (NF), and for the oligodendroglial progenitor marker,
      NG2. RESULTS.: Four weeks after injection, the retrograde delivery of the LacZ
      marker gene was identified in cervical spinal neurons and some glial cells,
      including oligodendrocytes in the white matter of the spinal cord, in both the
      twy/twy mouse and the heterozygous Institute of Cancer Research mouse (+/twy). In
      the compressed spinal cord of twy/twy mouse, AdV-BDNF gene transfection resulted
      in a significant decrease in the number of terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick end labeling-positive cells present in the spinal cord
      and a downregulation in the caspase apoptotic pathway compared with AdV-LacZ
      (control) gene transfection. There was a marked and significant increase in the
      areas of the spinal cord of AdV-BDNF-injected mice that were NF- and NG2
      immunopositive compared with AdV-LacZ-injected mice, indicating the increased
      presence of neurons and oligodendrocytes in response to BDNF transfection.
      CONCLUSION: Our results demonstrate that targeted retrograde BDNF gene delivery
      suppresses apoptosis in neurons and oligodendrocytes in the chronically
      compressed spinal cord of twy/twy mouse. Further work is required to establish
      whether this method of gene delivery may provide neuroprotective effects in other
      situations of compressive spinal cord injury.

PMID- 22648028
TI  - Predicting survival for surgery of metastatic spinal cord compression in prostate
      cancer: a new score.
AB  - STUDY DESIGN: We retrospectively analyzed prognostic factors for survival in
      patients with prostate cancer operated for metastatic spinal cord compression.
      OBJECTIVE: The aim was to obtain a clinical score for prediction of survival
      after surgery. SUMMARY OF BACKGROUND DATA: Survival prognosis is important when
      deciding about treatment of patients with metastatic spinal cord compression. The
      criteria for identifying patients with prostate cancer who may benefit from
      surgical treatment are unclear. METHODS: The study comprised 68 consecutive
      patients with prostate cancer operated for metastatic spinal cord compression at
      Umea University Hospital, Sweden. The indication for surgery was neurological
      deficit; 53 patients had hormone-refractory prostate cancer and 15 patients had
      previously untreated, hormone-naive prostate cancer. In 42 patients, posterior
      decompression was performed and 26 patients were operated with posterior
      decompression and stabilization. RESULTS: A new score for prediction of survival
      was developed on the basis of the results of survival analyses. The score
      includes hormone status of prostate cancer, Karnofsky performance status,
      evidence of visceral metastasis, and preoperative serum prostate-specific antigen
      (PSA). The total scores ranged from 0 to 6. Three prognostic groups were
      formulated: group A (n = 32) with scores 0-1; group B (n = 23) with scores 2-4,
      and group C (n = 12) with scores 5-6. The median overall survival was 3 (0.3-20)
      months in group A, 16 (1.8-59) months in group B, and more than half (7 of 12) of
      patients were still alive in group C. CONCLUSION: We present a new prognostic
      score for predicting survival of patients with prostate cancer after surgery for
      metastatic spinal cord compression. The score is easy to apply in clinical
      practice and may be used as additional support when making decision about
      treatment.

PMID- 22648029
TI  - Reliability of the thoracolumbar injury classification and severity score and
      comparison with the denis classification for injury to the thoracic and lumbar
      spine.
AB  - STUDY DESIGN: This study is a series of thoracic and lumbar spine fracture cases
      to assess the reliability of thoracolumbar injury classification and severity
      score (TLICS) in simulated clinical scenarios. OBJECTIVE: To determine the inter-
      and intraobserver reliability of TLICS compared with the Denis classification
      system, and to assess differences based on rater characteristics. SUMMARY OF
      BACKGROUND DATA: Thoracolumbar injury severity score and TLICS have been
      subjected to reliability testing using less robust statistical analysis. Both
      systems have demonstrated poor to good reliability, with particularly weak
      agreement on the status of the posterior ligamentous complex. METHODS: Fifty-four
      spine fracture cases were selected from a chart review. These cases were scored
      on 2 occasions by 11 experts using both TLICS and the Denis classification
      systems. Reliability was assessed using a generalizability coefficient. The
      primary outcome was interobserver reliability. Secondary outcomes were
      intraobserver reliability, difference between orthopedic and neurosurgeons, as
      well as trainees and consultants, and correlation with treatment recommendations.
      RESULTS: TLICS demonstrated good interobserver agreement of 0.73 to 0.74. The
      posterior ligamentous complex component was the least reliable. The Denis
      classification also demonstrated good reliability between observers, but was
      least reliable for flexion-distraction injuries. In addition, interobserver
      reliability between the Denis classification and TLICS morphology subcomponent
      was strong. TLICS also predicted the need for operative treatment as determined
      by the experts scoring the injuries. CONCLUSION: TLICS is a reliable system for
      assessing fractures of the thoracic and lumbar spine when used by experts.
      Similar to previous studies, the posterior ligamentous complex subcomponent score
      was the least reliable component. Reliability assessment using a generalizability
      coefficient is a robust method for validating fracture classifications.

PMID- 22648030
TI  - Safety and efficacy of 1-stage surgical treatment of congenital spinal deformity
      associated with split spinal cord malformation.
AB  - STUDY DESIGN: Retrospective clinical study. OBJECTIVE: The aim of this study was
      to evaluate retrospectively the safety and efficacy of 1-stage surgical treatment
      of 45 consecutive patients, who had progressive congenital spinal deformity
      associated with split spinal cord malformation (SSCM). SUMMARY OF BACKGROUND
      DATA: For correction of progressive congenital spinal deformity with SSCM, it has
      been reported that all SSCM should be operated on before any orthopedic
      intervention, and then surgery for correction and stabilization of the spinal
      deformity should be performed 3 to 6 months later. Recently, different viewpoints
      have been approved, and the common treatment of these 2 associated conditions
      needs to be re-evaluated. METHODS: Patients had 1-stage surgery. After exposure
      of the determined levels and placement of instruments, bony spur was resected in
      the patients of type 1; in patients of type 2, we did nothing to the SSCM. In the
      corrective stage of surgery, posterior fusion surgery was performed in 38
      patients; nonfusion surgery was performed in 7 patients. RESULTS: Thirty-six
      female patients and 9 male patients formed the basis of the study. The mean age
      was 14 years, and the mean follow-up period was 31 months. Type 1 SSCM was in 15
      patients, and type 2 SSCM was in 30 patients. Seven patients had progressive
      neurological deteriorations preoperatively. The mean major curves were corrected
      from an average of 73.7 degrees  to 33.5 degrees , with a correction rate of
      54.5%. The overall complication was transient, including 2 patients of
      neurological compromise and 1 patient of cerebrospinal fluid leakage. The average
      loss of correction at final follow-up was 2.5 degrees  for major curves.
      CONCLUSION: The 1-stage surgical treatment of congenital spinal deformity
      associated with SSCM provides a satisfactory option to improve the spinal
      deformity without significant complications effectively. Neurosurgical
      interventions are recommended to patients with type 1 SSCM before spinal
      deformity surgery; however, patients with type 2 SSCM can be treated safely
      without a need of neurosurgical intervention.

PMID- 22648031
TI  - ISSLS prize winner: Lumbar vertebral endplate lesions: associations with disc
      degeneration and back pain history.
AB  - STUDY DESIGN: An autopsy study. OBJECTIVE: To investigate associations between
      various types of lumbar endplate lesions, disc degeneration (DD), and back pain
      history. SUMMARY OF BACKGROUND DATA: The well-innervated vertebral endplate has
      been suspected as a source of back pain. Previously, we observed 4 types of
      lumbar endplate lesions with distinct morphological characteristics. Their roles
      in DD and back pain remain unclear. METHODS: From a lumbar spine archive of 136
      men (mean age, 52 yr), back pain, back injury, and occupation history data for 69
      subjects and discography data for 443 discs from 109 subjects were available for
      study. Back pain history was categorized as none, occasional, or frequent. DD was
      judged from discography. Endplate lesions were classified as Schmorl's nodes,
      fracture, erosion, or calcification, and lesion size was rated as none, small,
      moderate, or large. Associations between endplate lesions and DD, back pain
      history, back injury, and occupation history were examined. RESULTS: Presence of
      endplate lesions was associated with frequent (odds ratio [OR] = 2.57) but not
      occasional back pain. However, large endplate lesions were associated with both
      occasional (OR = 8.68) and frequent (OR = 17.88) back pain. This association
      remained after further controlling for DD. Also, the presence of each type of
      endplate lesion was associated with adjacent DD (OR = 2.40-9.71), with larger
      lesions associated with more severe DD. Endplate erosion lesions were more
      strongly associated with adjacent DD than Schmorl's nodes. Although back injury
      history was associated with the presence of fracture and erosion lesions, heavy
      occupation was associated with the presence of Schmorl's nodes. CONCLUSION:
      Endplate lesions are associated with back pain as well as being closely
      associated with adjacent DD, with a clear dosage effect. Different types of
      endplate lesions seem to have different magnitudes of associations with DD.
      Lumbar endplate lesions may be an important key to better understand both DD and
      back pain.

PMID- 22648032
TI  - Prognostic scoring systems for spinal metastases in the era of anti-VEGF
      therapies.
AB  - STUDY DESIGN: Spine Update on prognostic scoring systems for spinal metastases in
      the era of anti-vascular endothelial growth factor (VEGF) therapies. OBJECTIVE:
      To review and discuss the strengths and weaknesses of available scoring systems
      since the introduction of molecular targeted anticancer agents. SUMMARY OF
      BACKGROUND DATA: Molecular targeted anticancer agents have dramatically improved
      survival of patients in various cancers, including renal cancer. METHODS: Using
      prognostic scoring systems for spinal metastases and recent survival data of
      patients with cancers treated with anti-VEGF agents, a review was undertaken,
      evaluating the strengths and weaknesses of available prognostic scoring systems
      designed in the 1990s and early 2000s among patients treated with recent agents
      (available from 2005). RESULTS: All available prognostic scoring systems for
      spinal metastases include the primary tumor as a key variable. The estimation of
      life expectancy with these systems is inaccurate in view of recent survival data,
      as illustrated in renal cancer. The underestimation of life expectancy and
      subsequent inadequate treatment of spinal metastases may lead to dramatic
      alteration of the quality of life. CONCLUSION: The assessment of the available
      scores in recent cohorts of patients is mandatory to test their current validity
      and evidence the need for aggressive surgical management. New scoring systems
      taking into account the gain in survival induced by recent anticancer agents will
      likely be warranted in a close future.

PMID- 22648033
TI  - The discriminative properties of the SF-6D compared with the SF-36 and ODI.
AB  - STUDY DESIGN: Longitudinal cohort. OBJECTIVES: To determine the discriminate
      validity of the Short Form-6D (SF-6D) compared with the SF-36 in a cohort of
      patients with lumbar degenerative disorders. SUMMARY OF BACKGROUND DATA: Cost
      utility studies are important for the demonstration of comparative effectiveness
      of treatments for lumbar degenerative disorders. Multidimensional patient
      reported outcome tools including the SF-36 and Oswestry Disability Index (ODI)
      may be limited to measuring the utility of specific health care states. The
      evaluation of utility is based on single-index preference-based health state
      scales, such as the SF-6D. The loss of discriminative properties using a single
      index compared with a multidimensional score is unknown. METHODS: The cohort
      studies included 1104 patients who had decompression and lumbar fusion with
      complete ODI, SF-36, and SF-6D data at baseline and 2-year follow-up.
      Discriminative properties of the 3 measures were compared by computing the effect
      size (ES) and the standardized response mean (SRM). The larger the ES and SRM,
      the more sensitive to change the measure is. The relative validity (RV) statistic
      for each measure was also determined with the SF-6D as reference. Measures that
      are more sensitive than the SF-6D would have RVs greater than 1.0, those that are
      less sensitive would have RVs less than 1.0. RESULTS: The ODI had the greatest ES
      at 0.93 followed by the SF-6D at 0.88 and the SF-36 Physical Composite Score
      (PCS) at 0.85. The ODI also had the greatest standardized response mean at 0.73
      followed by the SF-6D at 0.70 and the SF-36 PCS at 0.57. The RV statistics for
      both the ODI (1.28) and the SF-36 PCS (1.32) were greater compared with the SF
      6D. The SF-36 bodily pain domain had the greatest ES (1.42), SRM (0.81), and RV
      (1.50). The general health domain had the lowest ES (0.21) and SRM (0.23),
      whereas mental health domain had the lowest RV. CONCLUSIONS: In this cohort of
      patients, using the single-index SF-6D produces a loss of discriminative
      properties compared with the SF-36 and ODI. However, this loss is small, because
      all the effect sizes remain large (>=0.80). Therefore, these losses should not
      preclude the use of the SF-6D compared with the SF-36 and may be preferred
      because it is more easily interpretable and less difficult to incorporate in
      economic evaluations.

PMID- 22648035
TI  - Cardiac findings in routine fetal autopsies: more than meets the eye?
AB  - OBJECTIVE: The main objective of this study was to evaluate the spectrum of
      cardiac anomalies found in routinely performed fetal autopsies and to establish
      the correlation between prenatal and postmortem diagnosis. STUDY DESIGN: A
      retrospective study of fetal autopsies was performed. Cases with cardiac
      anomalies were analyzed. Seven main categories were established and each case was
      assigned to a single group. Cardiac defects were also classified as isolated or
      with associated anomalies. In the cases with prenatal diagnosis, we performed a
      correlation between prenatal and postmortem findings. RESULTS: Abnormal cardiac
      findings were identified in 99 fetuses (13.6%). The two most common categories
      were septal defects and complex anomalies, each occurring in 21 fetuses (21.2%).
      Sixty-seven (67.7%) had associated anomalies. Septal anomalies were more frequent
      in cases with associated anomalies (p=0.012). Prenatal diagnosis had been
      performed in 50 cases. There was complete agreement between prenatal and
      postmortem diagnosis in 36 cases (72%), and major agreement with additional
      information in ten (20%). When the echocardiogram was not performed by a
      specialist, the number of cases classified with complete disagreement was higher
      (33.3% vs 2.4%) (p=0.002). CONCLUSION: The high prevalence of cardiac defects in
      lost pregnancies, some of them lacking prenatal diagnosis, highlights the
      importance of examining the heart in all cases.

PMID- 22648034
TI  - Cytokine expression in the epidural space: a model of noncompressive disc
      herniation-induced inflammation.
AB  - STUDY DESIGN: Animal study. OBJECTIVE: Development of an animal model for the
      study of biochemical changes that occur in the epidural space after
      intervertebral disc herniation. SUMMARY OF BACKGROUND DATA: Although strong
      evidence for an inflammatory component exists, the biochemical processes
      underlying pain after disc herniation remain unknown. METHODS: Epidural lavage
      was performed in 48 rats after L5 dorsal root ganglion exposure at baseline and
      3, 6, or 24 hours after placement of autologous nucleus pulposus (NP) (N = 15),
      saline (N = 15), or NP + an interferon-gamma antibody (anti-IFN-gamma; N = 18)
      directly onto the dorsal root ganglion. Multiplex assays quantifying interleukin
      (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNF
      alpha), IFN-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF)
      were performed. NP (N = 7) was also analyzed for these cytokines by placing NP
      into saline and measuring the relative concentration. RESULTS: Cytokines measured
      low at baseline (0-100 pg/mL) in all groups. Compared with saline, NP application
      caused IL-6 elevation, peaking at T = 3 hours, that was prevented by anti-IFN
      gamma. NP induced elevation of TNF-alpha, peaking at T = 24 hours and was
      prevented by anti-IFN-gamma. IFN-gamma was elevated after NP at T = 3 hours and T
      = 24 hours. IL-1alpha was similar after saline versus NP. The concentrations of
      IL-1beta and IL-10 were elevated at T = 3 hours, 6 hours, and 24 hours in all
      groups without between-groups difference. The level of IL-4 peaked at T = 3 hours
      in the NP group and was different than saline and NP + anti-IFN-gamma groups, but
      the time effect was insignificant. There was no change for GM-CSF. The
      concentration of cytokines measured in normal NP was less than 2 pg/mL for all
      cytokines except TNF-alpha. CONCLUSION: In this model of acute noncompressive
      disc herniation, NP caused the elevation of epidural IL-6, TNF-alpha, and IFN
      gamma--all attenuated by IFN-gamma blockade. IL-1beta and IL-10 were both
      significantly elevated by saline alone and their response was not prevented by
      IFN-gamma blockade. This model may prove useful for the study of the biochemical
      processes by which NP induces inflammation-induced nerve root irritation and
      radiculopathic pain.

PMID- 22648036
TI  - Relationships between structure and activity of carbon as a multifunctional
      support for electrocatalysts.
AB  - We report on new insights into the relationships between structure and activity
      of glassy carbon (GC), as a model material for electrocatalyst support, during
      its anodization in acid solution. Our investigation strongly confirms the role of
      CFGs in promotion of Pt activity by the "spill-over" effect related to CO(ads)
      for methanol electrooxidation (MEO) on a carbon-supported Pt catalyst. Combined
      analysis of voltammetric and impedance behaviour as well as changes in GC surface
      morphology induced by intensification of anodizing conditions reveal an intrinsic
      influence of the carbon functionalization and the structure of a graphene oxide
      (GO) layer on the electrical and electrocatalytic properties of activated GC.
      Although GO continuously grows during anodization, it structurally changes from
      being a graphite inter-layer within graphite ribbons toward a continuous GO
      surface layer that deteriorates the native structure of GC. As a consequence of
      the increased distance between GO-spaced graphite layers, the GC conductivity
      decreases until the case of profound GO exfoliation under drastic anodizing
      conditions. This exposes the native, yet abundantly functionalized, GC texture.
      While GC capacitance continuously increases with intensification of anodizing
      conditions, the surface nano-roughness and GO resistance reach the highest values
      at modest anodizing conditions, and then decrease upon drastic anodization due to
      the onset of GO exfoliation. We found for the first time that the activity of a
      GC-supported Pt catalyst in MEO, as one of the promising half-reactions in
      polymer electrolyte fuel cells, strictly follows the changes in GC nano-roughness
      and GO-induced GC resistance. The highest GC/Pt MEO activity is reached when
      optimal distance between graphite layers and optimal degree of GC
      functionalization bring the highest amount of CFGs into intimate contact with the
      Pt surface. This confirms the promoting role of CFGs in MEO catalysis.

PMID- 22648037
TI  - Understanding the effect of drug-resistant mutations of HIV-1 intasome on
      raltegravir action through molecular modeling study.
AB  - Raltegravir is the first FDA-approved drug targeting the strand transfer step of
      HIV-1 integration. However, the rapid emergence of viral strains that are highly
      resistant to raltegravir has become a critical problem. Unfortunately, the
      detailed molecular mechanism of how HIV-1 integrase (IN) mutations actually
      confer drug resistance is not well understood. In the present study, starting
      from our previously constructed complex of HIV-1 IN and viral DNA, we employed
      molecular dynamics (MD) simulation and molecular mechanics generalized Born
      surface area (MM-GBSA) calculation, to uncover the molecular mechanism behind the
      resistant mechanism of HIV-1 IN to raltegravir. The values of the calculated
      binding free energy follow consistently the experimentally observed ranking of
      resistance levels. A detailed analysis of the results of MD simulation suggests
      that the Tyr143 located in the 140s loop (e.g., residues from Gly140 to Gly149)
      is a key anchoring residue that leads to stable raltegravir binding. The decrease
      in the interaction at this residue is one of the key reasons responsible for the
      resistance of HIV-1 IN to raltegravir. Additionally, the calculation results also
      proved that the 3' adenosine flip in different conformations in the wild-type and
      mutant HIV-1 IN-viral DNA complexes play an important role in raltegravir
      binding. Our results could provide a structural and energetic understanding of
      the raltegravir-resistant mechanism at the atomic level and provide some new
      clues on how to design new drugs that may circumvent the known resistance
      mutations.

PMID- 22648038
TI  - Limb lengthening for post-traumatic shortening over a pre-implanted femoral
      locking plate.
AB  - Attempts have been made to refine techniques involved in distraction osteogenesis
      to improve patient compliance and reduce complications. The prolonged use of
      external fixators for limb lengthening is associated with a number of problems,
      and in addition patient satisfaction with a cumbersome external fixator may be
      low. To reduce the complication rate and facilitate early removal of the external
      fixator by protecting the regenerate bone, lengthening over an intramedullary
      nail is being increasingly described. These techniques have limitations when used
      in skeletally immature patients and carry a risk of deep intramedullary
      infection. Post-traumatic limb length discrepancy is not uncommon after high
      energy injuries are fixed in a shortened position secondary to bone loss. The
      plate applied at the time of injury may be incorporated into any subsequent
      lengthening process. A detailed description of the technique of lengthening over
      a pre-implanted distal femoral plate is followed by presentation of 2 case
      examples.

PMID- 22648040
TI  - A new ankle spanning fixator construct for distal tibia fractures:  optimizing
      visualization, minimizing pin problems, and protecting the heel.
AB  - Pilon and ankle fractures and ligamentous injuries about the ankle often require
      external fixation to allow for soft tissue stabilization before definitive
      surgery. Often used external fixator constructs can cause obscuring of the site
      of injury on radiographs, pin tract infections, loosening of calcaenal pin
      fixation, and heel ulcerations. A novel and simple technique of placing the
      calcaneal pins posteriorly and using a U-shaped bar allows for a construct that
      reduces or eliminates many of these drawbacks during the time it takes for soft
      tissue swelling to permit definitive fixation.

PMID- 22648039
TI  - Trans-syndesmotic fibular plating for fractures of the distal tibia and fibula
      with medial soft tissue injury: report of 6 cases and description of surgical
      technique.
AB  - This report presents a retrospective review of several cases of distal fractures
      of the tibia and fibula with significant injury to the medial soft tissues
      treated either primarily or in staged fashion with fixed-angle trans-syndesmotic
      fixation. This fixation strategy was used in an effort to minimize further
      surgical trauma and implant load in the zone of soft tissue injury. Ten patients
      were identified between September 2002 and November 2010 who presented to a level
      I trauma center with fractures of the distal tibia and fibula associated with
      open medial wounds (9 patients) or extensive closed medial degloving injury (1
      patient). They were all treated with trans-syndesmotic plating of the distal
      fibula. Two patients were lost to follow-up after initial treatment, and an
      additional 2 patients had follow-up durations of only 6.5 and 3 months,
      respectively. This left 6 patients with an average of 23.3 months of follow-up
      (range: 14-36 months). Radiographs and medical records were reviewed, and
      clinical and radiographic results were evaluated. All 6 patients had radiographic
      evidence of bony healing and had resumed weight bearing. Two patients required
      additional bone graft surgery to encourage healing, 1 of whom also required free
      flap coverage as a component of the nonunion repair. One patient resumed weight
      bearing earlier than instructed and experienced mild but acceptable loss of
      reduction. No patients developed wound infections of either the medial traumatic
      or lateral surgical wounds, although, as noted above, 1 of the patients with a
      nonunion required medial free-flap coverage as a component of the nonunion repair
      because of incompetent medial soft tissues. Trans-syndesmotic fixation has
      previously been described as providing enhanced fixation of diabetic and
      osteoporotic ankle fractures but has not, to our knowledge, been described for
      the treatment of higher energy traumatic injuries. Specifically, the valgus
      distal tibial fracture, frequently associated with medial traction wounds, can
      present challenges to the treating surgeon in terms of obtaining adequate
      fixation although minimizing wound complications associated with the soft tissue
      injury. In a select subset of injuries, trans-syndesmotic fixation can provide a
      viable means of obtaining and maintaining either definitive fixation or enhancing
      the provisional fixation supplied by spanning external fixation.

PMID- 22648041
TI  - Intra-operative correction of Taylor Spatial Frame without a computer.
AB  - The Taylor Spatial Frame (TSF) is a circular external fixator used to treat
      complex fractures and skeletal deformities. The device consists of 2 rings
      attached to bone by wires or half pins, connected by universal hinge joints to 6
      independent telescopic struts, creating a hexapod. The output piece is defined as
      the movable ring, which has 6 degree of freedom relative to the other ring, which
      is the base. With 6 degree of freedom, the movable platform is capable of moving
      in 3 linear directions and 3 angular directions singularly or in any combination.
      These hexapod devices require complex mathematical software programs to
      accurately control the output piece. In the case of the TSF, the deformity and
      positional frame parameters can be indentified on postoperative radiographs. They
      are then input into internet-based software to calculate strut adjustments
      required to achieve deformity correction. When treating fractures with the TSF,
      the rings can be connected using FastFx struts. These struts can be locked in
      position or left in a sliding mode (unlocked) allowing manual manipulation of the
      frame to acutely correct the position of the fracture fragments. This reduction
      is rarely perfect however and often requires further postoperative frame
      adjustments using software calculations. We describe an intra-operative method
      for accurately adjusting the frame in its locked mode without the need for
      software input.

PMID- 22648042
TI  - Orthogonal radiographic technique for radiographic visualization of coracoid
      process fractures and pericoracoid fracture extensions.
AB  - Radiographic visualization of coracoid process fractures is difficult due to the
      complex and variable 3-dimensional orientation of coracoid pillars. Failure to
      suspect an injury on preliminary radiographs has been described as a major reason
      for suboptimal management of these fractures. We describe a standardized method
      of patient positioning and radiographic beam angulation (orthogonal radiographic
      technique), to provide two roentgenographic views (Bhatia views) for
      visualization of individual coracoid pillars. The "superior pillar view (SPV)"
      demonstrates fractures involving the superior pillar, and peri-coracoid extension
      into the suprascapular notch; the "inferior pillar view (IPV)" is useful for
      fractures involving the inferior pillar (coracoid base), and their extension into
      the glenoid articular surface. Radiographs of 19 consecutive coracoid fractures,
      that were imaged using the described technique, were analyzed, and the results
      were used to suggest a radiographic method of grouping these injuries.

PMID- 22648043
TI  - Lateral sacral imaging in the morbidly obese.
AB  - Obesity can complicate surgical procedures by both adding to difficulty
      intraoperatively and increasing postoperative complications. Intraoperative
      imaging can be difficult on morbidly obese patients. We have noted specifically
      that in morbidly obese patients where the lateral sacrum cannot be visualized on
      the pre-operative scout computed tomography image, the lateral sacrum will not be
      able to be seen on intraoperative fluoroscopy. This is an important component of
      preoperative planning in morbidly obese patients with pelvic ring injuries.

PMID- 22648044
TI  - Effect of the host cell line on the vaccine efficacy of an attenuated porcine
      reproductive and respiratory syndrome virus.
AB  - The abilities of the modified-live Prime Pac (PP) strain of porcine reproductive
      and respiratory syndrome virus (PRRSV), propagated in either traditional simian
      cells (MARC-145) or in a novel porcine alveolar macrophage cell line (ZMAC), to
      confer pigs protection against subsequent PRRSV challenge were compared. Eight
      week-old pigs were injected with PP virus grown in one of the two cell types and
      then exposed 4 weeks later to the "atypical" PRRSV isolate NADC-20. Control
      animals were similarly challenged or remained PRRSV-naive. While the average
      adjusted body weight (aabw) of the strict control group increased 22% by 10 days
      post challenge (pc), this value for the non-vaccinated, challenged group dropped
      4%. In contrast, prior immunization with PP virus, regardless of its host cell
      source, ameliorated this effect by affording a >9% rise in aabw. Likewise, nearly
      equivalent protection was extended to both groups of vaccinates in regards to the
      temporal elimination of their pc clinical distress and viremia. However, the PP
      virus propagated in ZMAC cells appeared to be more efficacious since four of the
      six pigs receiving this biologic cleared the challenge virus from the their lungs
      by 10 days pc as compared to only one member of the other vaccinated group.
      Notably, the predominant quasispecies in the ZMAC cell-prepared PP virus stock
      contained a highly conserved N-glycosylation site at position 184 in its
      glycoprotein 2 while this entity was underrepresented in the MARC-145 cell grown
      biologic. Since glycoprotein 2 is involved in infectivity, such additional
      glycosylation may enhance virus replication in porcine alveolar macrophages.

PMID- 22648045
TI  - In vivo characterization of inflammatory biomarkers in swine and the impact of
      flunixin meglumine administration.
AB  - Non-steroidal anti-inflammatory drugs (NSAID) are a family of chemicals that
      function to reduce pain, fever, and inflammation, and they are commonly used in
      people and animals for this purpose. Currently there are no NSAIDs approved for
      the management of inflammation in swine due to a lack of validated animal models
      and suitable biomarkers to assess efficacy. A previous in vitro study examining
      biomarkers of inflammation identified fourteen genes that were significantly
      altered in response to Escherichia coli lipopolysaccharide (LPS)-induced
      inflammation. In the present study, five of those fourteen genes were tested in
      vivo to determine if the same effects observed in vitro were also observed in
      vivo. Plasma levels of prostaglandin E(2) (PGE(2)), an essential mediator of
      fever and inflammation, were also determined. Two groups of swine were stimulated
      with LPS with the second group also treated with flunixin meglumine. Blood was
      collected at 0, 1, 3, 6, 8, 24, and 48 h post LPS-stimulation. The RNA was
      extracted from the blood and quantitative real-time-PCR (qRT-PCR) was utilized to
      determine the expression patterns of CD1, CD4, serum amyloid A2 (SAA2), Caspase
      1, and monocyte chemoattractant protein 1 (MCP-1). The LPS-stimulated animals
      demonstrated a statistically significant alteration in expression of SAA2 and CD1
      at 3h post-stimulation. Flunixin meglumine treated animals' demonstrated reduced
      expression of CD1 in comparison to the LPS-stimulated swine at 24 and 48 h post
      LPS-stimulation. Flunixin meglumine treated animals exhibited reduced expression
      of SAA2 at 48 h post-stimulation compared to LPS-stimulated swine. Swine treated
      with LPS demonstrated statistically significant increases in plasma PGE(2) at 1h
      post-stimulation. Swine treated with flunixin meglumine had no increase in plasma
      PGE(2) levels at any time. These results demonstrate that PGE(2) production,
      along with two out of five genes (SAA2 and CD1) have the potential to serve as
      early biomarkers of inflammation as well as indicators of NSAID efficacy.

PMID- 22648047
TI  - Effect of juice and fermented vinegar from Hovenia dulcis peduncles on
      chronically alcohol-induced liver damage in mice.
AB  - The protective effects of juice and fermented vinegar from Hovenia dulcis
      peduncles on chronically ethanol-induced biochemical changes in male mice were
      investigated. Administration of ethanol (50%, v/v, 10 mL kg-1) to mice for 6
      weeks induced liver damage with a significant increase (P < 0.01) of the liver
      index, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl
      transferase (gamma-GT) in the serum and the hepatic lipid peroxidation (LPO)
      level. In contrast, administration of juice or fermented vinegar from Hovenia
      dulcis peduncles (10 mL kg-1 bw) along with alcohol significantly (P < 0.05)
      decreased the activities of the enzymes (AST, ALT and gamma-GT), liver index,
      concentrations of triglyceride (TG) and total cholesterol (TCH) in the serum and
      the hepatic TG and LPO levels. Mice treated with juice or fermented vinegar from
      Hovenia dulcis peduncles showed better profiles of the antioxidant systems with
      relatively higher glutathione (GSH) content, total superoxide dismutase (T-SOD),
      catalase (CAT) and glutathione peroxidase (GSH-Px) activities. All these results
      were accompanied by histological observations in liver. The results demonstrate
      that both of the juice and fermented vinegar from Hovenia dulcis peduncles have
      beneficial effects in reducing the adverse effect of alcohol.

PMID- 22648046
TI  - Increased expression of fractalkine and its receptor CX3CR1 in canine
      inflammatory bowel disease and their possible role in recruitment of
      intraepithelial lymphocytes.
AB  - The interaction between fractalkine/CX(3)CL1 and its receptor CX(3)CR1 has been
      reported to play an important role in various human inflammatory diseases,
      including inflammatory bowel disease (IBD) mediated by lymphocyte
      chemoattraction. The objective of this study was to investigate the role of
      fractalkine and CX(3)CR1 in lymphocyte migration in canine IBD. IBD was diagnosed
      in 34 dogs, and 19 healthy beagles were used as normal controls. We quantified
      intestinal mRNA and protein expression of fractalkine and CX(3)CR1 by real-time
      RT-PCR and ELISA, respectively, and examined the localization of fractalkine in
      canine intestine by immunohistochemistry. The expression of CX(3)CR1 and surface
      antigens on peripheral blood mononuclear cells (PBMCs) and intraepithelial
      lymphocytes (IELs) was analyzed by flow cytometry. Intestinal fractalkine and
      CX(3)CR1 mRNA was significantly up-regulated in IBD dogs compared with the
      healthy control dogs. In addition, fractalkine expression on intestinal
      epithelial cells was significantly increased in the intestinal mucosa of IBD dogs
      compared with the healthy dogs. CX(3)CR1(+) PBMCs were significantly elevated in
      IBD dogs and positively correlated with the histopathological severity of IELs
      infiltration. These CX(3)CR1(+) PBMCs predominantly expressed markers for
      cytotoxic T cells. Almost all IELs expressed CD3, and the majority of cells
      expressed CD8 rather than CD4, which was analogous to the CX(3)CR1(+) PBMCs.
      These results suggest that the fractalkine-CX(3)CR1 interaction may contribute to
      the pathogenesis of canine IBD through migration of IELs.

PMID- 22648048
TI  - Ameliorating effect of fish oil on acrylamide induced oxidative stress and
      neuronal apoptosis in cerebral cortex.
AB  - Acrylamide (ACR) is a known industrial toxic chemical that produce neurotoxicity
      characterized by progressive neuronal degeneration. This study was designed to
      investigate the protective effect of fish oil on ACR-induced neuronal damage in
      Wistar rats. ACR enhances the production of reactive oxygen species and
      potentially affects brain. ACR administered rats showed increased levels of lipid
      peroxidative product, protein carbonyl content, hydroxyl radical and
      hydroperoxide which were significantly modulated by the supplementation of fish
      oil. The activities of enzymic antioxidants and levels of reduced glutathione
      were markedly lowered in ACR-induced rats; fish oil treatment augmented these
      antioxidant levels in cortex. Free radicals generated during ACR administration
      reduced the activities of membrane adenosine triphosphatases and acetylcholine
      esterase. Fish oil enhanced the activities of these enzymes near normal level.
      Histological observation represented the protective role of fish oil in ACR
      induced neuronal damage. Fish oil reduced the ACR-induced apoptosis through the
      modulation in expressions of B-cell lymphoma 2 (Bcl2)-associated X protein and
      Bcl2-associated death promoter. Further, fish oil increases the expression of
      heat shock protein 27 (Hsp27) in ACR-induced rats. This study provides evidence
      for the neuroprotective effect of fish oil on ACR-induced neurotoxicity by
      reducing oxidative stress and apoptosis with modulation in the expression of
      Hsp27.

PMID- 22648049
TI  - Detection of non-alcoholic steatohepatitis in patients with morbid obesity before
      bariatric surgery: preliminary evaluation with acoustic radiation force impulse
      imaging.
AB  - OBJECTIVE: To investigate the utility of acoustic radiation force impulse (ARFI)
      imaging, with the determination of shear wave velocity (SWV), to differentiate
      non-alcoholic fatty liver disease (NAFLD) from non-alcoholic steatohepatitis
      (NASH) in patients with morbid obesity before bariatric surgery. METHODS: Thirty
      two patients with morbid obesity were evaluated with ARFI and conventional
      ultrasound before bariatric surgery. The ARFI and ultrasound results were
      compared with liver biopsy findings, which is the reference standard. The
      patients were classed according to their histological findings into three groups:
      group A, simple steatosis; group B, inflammation; and group C, fibrosis. RESULTS:
      The median SWV was 1.57 +/- 0.79 m/s. Hepatic alterations were observed in the
      histopathological findings for all the patients in the study (100 %), with the
      results of the laboratory tests proving normal. Differences in SWV were also
      observed between groups A, B and C: 1.34 +/- 0.90 m/s, 1.55 +/- 0.79 m/s and 1.86
      +/- 0.75 m/s (P < 0.001), respectively. The Az for differentiating NAFLD from
      NASH or fibrosis was 0.899 (optimal cut-off value 1.3 m/s; sensitivity 85 %;
      specificity 83.3 %). CONCLUSION: The ARFI technique is a useful diagnostic tool
      for differentiating NAFLD from NASH in asymptomatic patients with morbid obesity.
      KEY POINTS : * Acoustic radiation force impulse imaging provides ultrasonic shear
      wave velocity measurements. * SWV measurements were higher in patients with
      inflammation or fibrosis than NAFLD. * ARFI differentiates NAFLD from NASH in
      patients with morbid obesity. * Results suggest that ARFI can detect NASH in
      asymptomatic morbidly obese patients.

PMID- 22648052
TI  - Cyclic lipopeptide profile of the plant-beneficial endophytic bacterium Bacillus
      subtilis HC8.
AB  - In a previous study (Malfanova et al. in Microbial Biotech 4:523-532, 2011), we
      described the isolation and partial characterization of the biocontrol endophytic
      bacterium B. subtilis HC8. Using thin-layer chromatography, we have detected
      several bioactive antifungal compounds in the methanolic extract from the acid
      precipitated supernatant of HC8. In the present study, we have further analyzed
      this methanolic extract using liquid chromatography-mass spectrometry. Based on
      the comparison of retention times and molecular masses with those of known
      antifungal compounds, we identified three families of lipopeptide antibiotics.
      These include four iturins A having fatty acyl chain lengths of C14 to C17, eight
      fengycins A (from C14 to C18 and from C15 to C17 containing a double bond in the
      acyl chain), four fengycins B (C15 to C18), and five surfactins (C12 to C16).
      Evaluation of the antifungal activity of the isolated lipopeptides showed that
      fengycins are the most active ones. To our knowledge, this is the first report of
      an endophytic Bacillus subtilis producing all three major families of lipopeptide
      antibiotics containing a very heterogeneous mixture of homologues. The questions
      remain open which of these lipopeptides (1) are being produced during interaction
      with the plant and (2) are contributing to the biocontrol activity of HC8.

PMID- 22648054
TI  - Long-term stability of GHB in post-mortem samples and samples from living
      persons, stored at -20 degrees C, using fluoride preservatives.
AB  - PURPOSE: Reanalyses are frequently requested in forensic toxicology, and
      knowledge of the stability of drugs in biological samples is of major importance
      for the interpretation of the toxicological findings. Currently, the literature
      on stability of gammahydroxybutyrate (GHB) in blood samples from living subjects
      and in post-mortem blood is limited. The purpose of this study was to evaluate
      the long-term stability of GHB in both blood samples from persons suspected of
      drug use and post-mortem blood samples. METHODS: A total of 59 reanalyses were
      performed in whole blood samples, 27 samples from living subjects and 32 samples
      taken at autopsies. The samples were stored in the freezer between 0.4 and 7.2
      years at -20 degrees C in vials containing preservatives. Analyses were performed
      by GC-FID, and cut-off level was 10.3 mg/L. The concentrations in 22 of the
      samples were below cut-off. RESULTS: The mean change in concentration between
      initial analysis and reanalysis was -0.8% for the positive samples from living
      persons and -7.1% for the positive post-mortem samples. Changes ranged from 
      32.4% to 21.0% for samples from living and from -30.4% to 34.4% for post-mortem
      samples. All negative samples were still negative at the time of reanalysis.
      CONCLUSION: Reanalysis of these forensic whole blood samples stored several years
      at -20 degrees C with fluoride preservation did not exhibit changes in GHB
      concentrations of practical significance for the interpretation of toxicological
      findings.

PMID- 22648053
TI  - Stationary phase in Trypanosoma cruzi epimastigotes as a preadaptive stage for
      metacyclogenesis.
AB  - Trypanosoma cruzi is a species of parasitic protozoa that causes American
      trypanosomiasis or Chagas disease. These parasites go through a complex life
      cycle in Triatominae insects and vertebrate hosts. Epimastigotes are replicative
      forms that colonize the digestive tract of the vector and can be cultured in
      axenic media. The growth curve of epimastigotes allows assessment of differences
      in cells undergoing growth rate transitions from an exponential growth to a
      stationary phase. Since the classical descriptions of T. cruzi, it has been noted
      that the growth curve of epimastigotes in culture can give rise, in the
      stationary phase, to nonreplicating forms of metacyclic trypomastigotes.
      Metacyclogenesis therefore regards to the development process by which
      epimastigote transform into infective metacyclic trypomastigotes. In nature,
      these metacyclic forms allow the spread of Chagas disease when transmitted from
      an infected vector to a vertebrate host. This work reviews cellular phenomena
      that occur during the growth rate transitions of epimastigotes in culture, which
      may be related to very early physiological conditions for metacyclogenesis. Many
      of these events have not been thoroughly investigated. Their analysis can
      stimulate new hypotheses and future research in an important area not fully
      exploited.

PMID- 22648055
TI  - "Legal highs"--toxicity in the clinical and medico-legal aspect as exemplified by
      suicide with bk-MBDB administration.
AB  - The easily available "legal highs", which are products containing psychoactive
      substances, such as cathinones, piperazines and synthetic cannabinoids, are
      abused by adolescents in Poland and in the world as alternatives to classic
      drugs, such as amphetamines or marijuana. The majority of these potentially
      dangerous substances are still legal and they are associated with a risk of
      severe poisoning or even death, and provide new challenges in clinical and
      forensic toxicological practice. Investigations in the field of "designer drugs"
      may be well illustrated by the case of a suicide of a 21-year old male who
      ingested a specified dose of a preparation called "Amphi-bi-a" that contains bk
      MBDB, chemically 2-methylamino-1-(3,4-methylenedioxyphenyl) butan-1-one, which
      belongs to the cathinone group, as a synthetic euphoric empathogen and
      psychoactive stimulant that is chemically similar to MDMA. It is one of more
      common components of "legal highs" examined in Poland and other countries. The
      documentation of the case includes a clinical assessment of the patient's health
      status performed during his almost 4-h hospitalization before death, autopsy and
      histological examinations supported by toxicological findings revealing bk-MBDB
      at extremely high concentrations (at 20 mg/l in the blood and 33 mg/kg in the
      liver); hence, this body of evidence contributes to knowledge in the field of
      "designer drugs". Inventions of designers of new psychoactive xenobiotics, which
      are much in demand, especially in view of the dynamic Internet marketing, which
      drums up narcobusiness, must be balanced by a national strategy developed by
      medical, legal and educational circles in the modern civilized world in order to
      prevent the spreading of the phenomenon.

PMID- 22648056
TI  - A case of fatal cervical discoligamentous hyperextension injury without fracture:
      correlation of postmortem imaging and autopsy findings.
AB  - We present a case of fatal cervical discoligamentous hyperextension injury
      without fracture. Postmortem computed tomography (PMCT) and postmortem magnetic
      resonance imaging (PMMRI) disclosed cervical instability and spinal cord injury
      in the absence of fracture, which was confirmed by autopsy. Cervical
      discoligamentous injury without fracture may be unnoticeable on PMCT because
      signs of cervical misalignment change depending on the posture of the neck at the
      time of postmortem imaging. Because of its greater sensitivity for soft tissue
      injury, PMMRI is especially useful for detecting pathological changes in cases of
      death due to cervical discoligamentous injury. In this paper, findings on
      postmortem imaging for this injury are described in detail and correlated with
      findings on autopsy.

PMID- 22648058
TI  - Better understanding of minimizing infectious complications after transrectal
      prostate biopsy.

PMID- 22648059
TI  - Clinicopathologic features of prostate cancer in patients diagnosed by age 45 who
      underwent radical prostatectomy.

PMID- 22648057
TI  - Genomics and epigenomics of the human glycome.
AB  - The majority of all proteins are glycosylated and glycans have numerous important
      structural, functional and regulatory roles in various physiological processes.
      While structure of the polypeptide part of a glycoprotein is defined by the
      sequence of nucleotides in the corresponding gene, structure of a glycan part
      results from dynamic interactions between hundreds of genes, their protein
      products and environmental factors. The composition of the glycome attached to an
      individual protein, or to a complex mixture of proteins, like human plasma, is
      stable within an individual, but very variable between individuals. This
      variability stems from numerous common genetic polymorphisms reflecting in
      changes in the complex biosynthetic pathway of glycans, but also from the
      interaction with the environment. Environment can affect glycan biosynthesis at
      the level of substrate availability, regulation of enzyme activity and/or
      hormonal signals, but also through gene-environment interactions. Epigenetics
      provides a molecular basis how the environment can modify phenotype of an
      individual. The epigenetic information (DNA methylation pattern and histone code)
      is especially vulnerable to environmental effects in the early intrauterine and
      neo-natal development and many common late-onset diseases take root already at
      that time. The evidences showing the link between epigenetics and glycosylation
      are accumulating. Recent progress in high-throughput glycomics, genomics and
      epigenomics enabled first epidemiological and genome-wide association studies of
      the glycome, which are presented in this mini-review.

PMID- 22648061
TI  - Questionable link between normo- to microalbuminuria and home-measured blood
      pressure variability in hypertension.

PMID- 22648060
TI  - Mapping genetic determinants of kidney damage in rat models.
AB  - During the last two decades, significant progress in our understanding of the
      development of kidney diseases has been achieved by unravelling the mechanisms
      underlying rare familial forms of human kidney diseases. Due to the genetic
      heterogeneity in human populations and the complex multifactorial pathogenesis of
      the disease phenotypes, the dissection of the genetic basis of common chronic
      kidney diseases (CKD) remains a difficult task. In this regard, several inbred
      rat models provide valuable complementary tools to uncover the genetic basis of
      complex renal disease phenotypes that are related to common forms of CKD. In this
      review, data obtained in nine experimental rat models, including the Buffalo
      (BUF), Dahl salt-sensitive (SS), Fawn-hooded hypertensive (FHH), Goto-Kakizaki
      (GK), Lyon hypertensive (LH), Munich Wistar Fromter (MWF), Sabra hypertension
      prone (SBH), spontaneously hypertensive rat (SHR) and stroke-prone spontaneously
      hypertensive rat (SHRSP) inbred strains, that contributed to the genetic
      dissection of renal disease phenotypes are presented. In this panel of inbred
      strains, a large number of quantitative trait loci (QTL) linked to
      albuminuria/proteinuria and other functional or structural kidney abnormalities
      could be identified by QTL mapping analysis and follow-up studies including
      consomic and congenic rat lines. The comprehensive exploitation of the genotype
      renal phenotype associations that are inherited in this panel of rat strains is
      suitable for making a significant contribution to the development of an
      integrated approach to the systems genetics of common CKD.

PMID- 22648062
TI  - Secondary hypertrophic pachymeningitis in antiphospholipid syndrome.
AB  - This report describes a rare case of hypertrophic pachymeningitis secondary to
      antiphospholipid syndrome in a 37-year-old woman. The patient had a history of
      antiphospholipid syndrome and developed hypertrophic pachymeningitis
      subsequently. Pathological examination of the dura mater showed not only fibrous
      thickening, the typical finding of hypertrophic pachymeningitis, but also
      thrombosis in the dural microvessels and T cell infiltration without B cell or
      plasma cell infiltration, suggesting cell-mediated immunity. The dural thickening
      spontaneously improved and did not deteriorate during corticosteroid therapy. The
      histological findings and spontaneous remission observed in this case might be
      characteristic of secondary hypertrophic pachymeningitis with antiphospholipid
      syndrome. Further investigations are necessary to elucidate the pathophysiology
      of this novel type of hypertrophic pachymeningitis.

PMID- 22648063
TI  - Early hypospadias repair: the contributions of Harvey Cushing.
AB  - PURPOSE: The early evolution of surgical reconstructive techniques has been well
      documented in the literature. However, a review of the Johns Hopkins hospital
      surgical files revealed an interesting participant in early hypospadias repair:
      Harvey Cushing (1869-1939). METHODS: Following IRB approval, we reviewed the
      surgical records from 1896 to 1912 and selected from among his non-neurosurgical
      patients, one case of first-stage hypospadias repair. RESULTS: Cushing operated
      upon the 21-year-old patient, performing a first-stage repair of hypospadias, in
      conjunction with a repair of a right inguinal hernia. The patient was discharged
      following a second stage operation. At that time, the patient was in good
      condition and was voiding appropriately. There was no further follow-up.
      CONCLUSION: The repair of hypospadias evolved through the work of European
      surgeons, from the mid-eighth century through the early nineteenth century. The
      case we report here illustrates Cushing's early work in the fields of urologic
      and plastic surgery.

PMID- 22648064
TI  - Analysis of medication information exchange at discharge from a Dutch hospital.
AB  - BACKGROUND: At hospitalisation and discharge the risk of errors in medication
      information transfer is high. OBJECTIVE: To study the routes by which medication
      information is transferred during discharge from Deventer Hospital, and to
      improve medication information transfer. SETTING: Eight hospital wards of the
      Deventer Hospital. METHOD: From December 6 to 17th 2010, the following data was
      recorded across eight hospital wards: the identification number of discharged
      patients, the date of discharge and the route by which medication information was
      transferred. The possible route categories recorded were the Pharmacy Service
      Point, the hospital's public pharmacy, and "other" routes (which had to be
      specified). Validation of the data was performed by cross-checking the
      information collected by the hospital's Admission Office, the Pharmacy Service
      Point and the hospital's public pharmacy, in addition to electronic patient
      files, interviews with ward staff and, where necessary, interviews with the
      concerned patients. Main outcome measure Route of medication information transfer
      at discharge in all discharged patients. RESULTS: A total of 629 patients were
      included in the study. The routes of transfer were: Pharmacy Service Point 281
      patients (44 %), the hospital's public pharmacy 54 patients (9 %), and other
      routes 44 patients (7 %). Other routes were most recorded at the children's ward,
      the short stay and cardiology ward. In 250 patients (40 %), there was no transfer
      of information by the Pharmacy Service Point because they were registered as
      using no medication or as experiencing no medication changes during
      hospitalisation. CONCLUSION: Medication information was transferred for 53 % of
      the discharged patients, which is close to the maximum achievable result. Further
      improvement of medication transfer in Deventer Hospital can be made by adjusting
      the current procedure and by educating the ward staff about the importance and
      the clinical practice of this procedure.

PMID- 22648066
TI  - Incisional hernia recurrence through genomic profiling: a pilot study.
AB  - PURPOSE: Although situational risk factors for incisional hernia formation are
      known, the methods used to determine who would be most susceptible to develop one
      are unreliable. We hypothesized that patients with recurrent incisional hernias
      may possess unique gene expression profiles. METHODS: Skin and intact fascia were
      collected from 15 normal control (NC) patients with no hernia history and 18
      patients presenting for recurrent incisional hernia (RH) repair. Microarray
      analysis was performed using whole genome microarray chips on NC (n = 8) and RH
      (n = 9). These samples were further investigated using a pathway-specific PCR
      array containing fibrosis-related genes. RESULTS: Microarray data revealed
      distinct differences in the gene expression profiles between RH and NC patients.
      One hundred and sixty-seven genes in the skin and 7 genes in the fascia were
      differentially expressed, including 8 directly involved in collagen synthesis. In
      particular, GREMLIN1, or bone morphogenetic protein antagonist 1, was under
      expressed in skin (fold = 0.49, p < 10(-7), q = 0.0009) and fascia (fold = 0.23,
      p < 10(-4), q = 0.095) of RH patients compared with NC. The PCR array data
      supported previous reports of decreased collagen I/III ratios in skin of RH
      versus NC (mean = 1.51 +/- 0.73 vs. mean = 2.26 +/- 0.99; one-sided t test, p =
      0.058). CONCLUSION: To our knowledge, this is the first microarray-based analysis
      to show distinct gene expression profiles between the skin and fascia of RH and
      NC patients and the first report of an association between GREMLIN1 and
      incisional hernia formation. Our results suggest that gene expression profiles
      may act as surrogate markers that stratify patients into different groups at risk
      for hernia development prior to their initial surgery.

PMID- 22648067
TI  - Molecular optoelectronics: the interaction of molecular conduction junctions with
      light.
AB  - The interaction of light with molecular conduction junctions is attracting
      growing interest as a challenging experimental and theoretical problem on one
      hand, and because of its potential application as a characterization and control
      tool on the other. It stands at the interface between two important fields,
      molecular electronics and molecular plasmonics and has attracted attention as a
      challenging scientific problem with potentially important technological
      consequences. Here we review the present state of the art of this field, focusing
      on several key phenomena and applications: using light as a switching device,
      using light to control junction transport in the adiabatic and non-adiabatic
      regimes, light generation in biased junctions and Raman scattering from such
      systems. This field has seen remarkable progress in the past decade, and the
      growing availability of scanning tip configurations that can combine optical and
      electrical probes suggests that further progress towards the goal of realizing
      molecular optoelectronics on the nanoscale is imminent.

PMID- 22648068
TI  - Density dependence: an ecological Tower of Babel.
AB  - The concept of density dependence represents the effect of changing population
      size on demographic rates and captures the demographic role of social and trophic
      mechanisms (e.g. competition, cooperation, parasitism or predation). Ecologists
      have coined more than 60 terms to denote different statistical and semantic
      properties of this concept, resulting in a formidable lexicon of synonymies and
      polysemies. We have examined the vocabulary of density dependence used in the
      modern ecological literature from the foundational lexicon developed by Smith,
      Allee, Haldane, Neave and Varley. A few simple rules suffice to abate
      terminological inconsistency and to enhance the biological meaning of this
      important concept. Correct citation of original references by ecologists and
      research journals could ameliorate terminological standards in our discipline and
      avoid linguistic confusion of mathematically and theoretically complex patterns.

PMID- 22648070
TI  - Cytotoxicity and genotoxicity of versicolorins and 5-methoxysterigmatocystin in
      A549 cells.
AB  - Aspergillus versicolor and A. flavus are primary colonizers in damp dwellings,
      and they produce sterigmatocystin (ST) and aflatoxin B1 (AFB(1)), respectively.
      These hepatotoxic and carcinogenic mycotoxins and their precursors and derivates
      possess a furofuran ring, which has proven responsible for their toxicity. The
      aim of this study was to investigate the cytotoxicity and genotoxicity of
      versicolorin A (VER A) and versicolorin B (VER B), as the furofuran precursors of
      aflatoxins and ST, and of 5-methoxysterigmatocystin (5-MET-ST), a methoxy
      derivative of ST, in human adenocarcinoma lung cells A549. The IC(50) values of
      the tested compounds were obtained by the cell proliferation MTT test as follows:
      109 +/- 3.5 MUM (VER A), 172 +/- 4 MUM (VER B) and 181 +/- 2.6 MUM (5-MET-ST).
      The comet assay and micronucleus test were used to assess their genotoxic
      potential after 24 h of treatment with concentrations corresponding to 1/2 and
      1/4 IC(50) in comparison with AFB(1) and ST, applied in concentrations
      corresponding to 1/2 IC(50), as previously determined in A549 cells. DNA damage
      parameters assessed by the comet assay were tail length, tail intensity and tail
      moment, while the level of DNA damage in the micronucleus test was evaluated by
      the number of formed micronuclei (MN), nuclear buds (NB) and nucleoplasmic
      bridges (NPB) in 1,000 binucleated cells. Considering the three comet parameters,
      all applied toxins exerted significant DNA damage compared to the control, while
      ST and VER B produced the highest DNA damage. All toxins provoked a statistically
      significant increase in MN, and a slightly decreased formation of NB and NPB.
      AFB(1), ST and 20 MUM VER A showed a statistically significant increase in all
      three micronucleus parameters compared to the control, and the highest increase
      in the number of MN occurred in cells treated with 50 MUM VER A. The differences
      between results obtained by the micronucleus test and comet assay could be
      explained by the fact that the micronucleus detects irreversible DNA damage,
      which is usually correlated with the previously determined cytotoxic potential of
      the AFB(1) precursors.

PMID- 22648071
TI  - UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for puerarin
      metabolism in human liver microsomes.
AB  - Puerarin has multiple pharmacological effects and is widely prescribed for
      patients with cardiovascular diseases, including hypertension, cerebral ischemia,
      myocardial ischemia, diabetes mellitus, and arteriosclerosis. While puerarin is a
      useful therapeutic agent, its mechanisms of action have not been well defined.
      Understanding puerarin metabolism, in particular its interactions with
      metabolizing enzymes, will contribute to our understanding of its toxic and
      therapeutic effects and may help to elucidate potential negative drug-drug
      interactions. In this study, the major metabolite of puerarin was obtained from
      the urine of rats administered puerarin, by a semi-preparative high-performance
      liquid chromatography method. The major metabolite was identified as puerarin-7-O
      glucuronide. In vitro, we used a UDP-glucuronosyltransferase (UGT) reaction
      screening method with 12 recombinant human UGTs to demonstrate that formation of
      puerarin-7-O-glucuronide was catalyzed by UGT1A1, 1A9, 1A10, 1A3, 1A6, 1A7, and
      1A8. UGT1A1, 1A9, and 1A10 significantly catalyzed puerarin-7-O-glucuronide
      formation, and the activity of UGT1A1 was significantly higher than those of 1A9
      and 1A10. The V (max) of UGT1A1 was two- to threefold higher than the levels of
      UGT1A9 or 1A10, with a lower K ( m ) value and a higher V (max)/K ( m ) value.
      The kinetics of puerarin-7-O-glucuronide formation catalyzed by UGT1A1 were
      similar to those of the pooled human liver microsomes (HLMs), with V (max) values
      of 186.3 and 149.2 pmol/min/mg protein, and K ( m ) values of 811.3 and 838.9
      MUM, respectively. Furthermore, bilirubin and beta-estradiol, probe substrates
      for UGT1A1, significantly inhibited the formation of puerarin-7-O-glucuronide in
      HLMs.

PMID- 22648069
TI  - Estrogen receptors and human disease: an update.
AB  - A myriad of physiological processes in mammals are influenced by estrogens and
      the estrogen receptors (ERs), ERalpha and ERbeta. As we reviewed previously,
      given the widespread role for estrogen in normal human physiology, it is not
      surprising that estrogen is implicated in the development or progression of a
      number of diseases. In this review, we are giving a 5-year update of the
      literature regarding the influence of estrogens on a number of human cancers
      (breast, ovarian, colorectal, prostate, and endometrial), endometriosis,
      fibroids, and cardiovascular disease. A large number of sophisticated
      experimental studies have provided insights into human disease, but for this
      review, the literature citations were limited to articles published after our
      previous review (Deroo and Korach in J Clin Invest 116(3):561-570, 2006) and will
      focus in most cases on human data and clinical trials. We will describe the
      influence in which estrogen's action, through one of or both of the ERs, mediates
      the aforementioned human disease states.

PMID- 22648072
TI  - Kupffer cells suppress perfluorononanoic acid-induced hepatic peroxisome
      proliferator-activated receptor alpha expression by releasing cytokines.
AB  - Kupffer cells (KCs) have been demonstrated to play a role in the regulation of
      intra-hepatic lipid metabolism through the synthesis and secretion of
      biologically active products. The involvement of KCs in the disturbance of lipid
      metabolism that induced by perfluorononanoic acid (PFNA), a known agonist of the
      peroxisome proliferator-activated receptor alpha (PPARalpha), was investigated in
      this study. Rats were exposed to PFNA or PFNA combined with gadolinium chloride,
      an inhibitor of KCs, for 14 days. PFNA exposure dose-dependently increased
      absolute and relative liver weights, induced triglyceride accumulation, up
      regulated the expression of both SERBP-1c and PPARalpha, and stimulated the
      release of TNFalpha and IL-1beta. Inactivation of KCs markedly lowered TNFalpha
      and IL-1beta level, enhanced PFNA-induced expression of PPARalpha and its target
      genes, and reduced liver triglyceride levels. In vitro, PFNA-induced expression
      of PPARalpha in primary cultured hepatocytes was suppressed by recombinant rat
      TNFalpha and IL-1beta. However, inhibition of the NF-kappaB pathway prevented
      this. Transient transfection and promoter analysis further revealed that these
      two cytokines and NF-kappaB were coordinately involved in the suppression of
      PPARalpha promoter activity. Our data demonstrate that TNFalpha and IL-1beta
      released from KCs following PFNA exposure can suppress the expression of
      PPARalpha via NF-kappaB pathway, which partially contribute to the evident
      accumulation of triglycerides in rat liver.

PMID- 22648073
TI  - Overview. Type I interferons as primers, activators and inhibitors of innate and
      adaptive immune responses.

PMID- 22648076
TI  - Congenital brain tumors in a series of 56 patients.
AB  - INTRODUCTION: Central nervous system tumors diagnosed before the end of the first
      year of life differ from those found in older children and in adults. The
      differences include mode of clinical presentation, anatomical distribution,
      histopathological diagnoses, response to therapy, and outcome. MATERIALS AND
      METHODS: The material consists of 56 children (23 girls and 33 boys), aged at
      recognition 32 Hbd-12 months. We reviewed charts and MR exams according to age of
      the onset of symptoms, location of tumors, treatment, histopathology, and
      outcomes. Data of the outcome were analyzed using Kaplan-Meier plots and chi
      square test. RESULTS: Eleven cases were recognized before 6 weeks of life, 24
      before the age of 6 months, and 21 were diagnosed up to the end of 1 year of age.
      Thirty-eight tumors were located in the supratentorial compartment; 18 were
      infratentorial. Median age of tumors' recognition was 5.2 months; 4.3 months for
      supratentorial and 7.2 months for infratentorial tumors. We found 18 glial cell
      tumors (high and low grade), 15 embryonal tumors, and 12 choroid plexus tumors.
      CONCLUSIONS: The outcome of congenital CNS tumors depends on the size, location,
      time of diagnosis, histological type of the tumor, and therapeutic option.
      Neurosurgical procedures are necessary in most cases. Despite the notable
      advances in therapy, the outcome remains poor.

PMID- 22648077
TI  - Concurrent anatomic hemispherectomy and thalamic arteriovenous malformation
      resection.

PMID- 22648079
TI  - Magnetic resonance imaging of inflammatory myopathies.
AB  - The following article reviews the role of magnetic resonance imaging (MRI) in
      patients with idiopathic inflammatory myopathies (IIMs), focusing on the 3 major
      types of IIM: polymyositis, dermatomyositis, and inclusion-body myositis. After a
      brief introduction with general information about IIM, we will discuss the
      reasons why MRI plays an important role in the diagnosis and management of
      patients with polymyositis, dermatomyositis, and inclusion-body myositis.
      Magnetic resonance imaging can confirm the diagnosis and can help to phenotype
      the disease. Moreover, the support of MRI is important in addressing the muscle
      biopsy site and in reducing the high false-negative rate of biopsy when performed
      in a blind fashion. In monitoring therapy, MRI can add important information
      about the activity of the muscle disease and can identify cases where continued
      immunosuppressive therapy is no longer warranted owing to complete fatty
      replacement of the muscles. Lastly, we provide an overview about some advanced
      MRI techniques that focus more on function than on morphology of muscle.

PMID- 22648078
TI  - Unusual complications and mechanism: migration of the distal catheter into the
      heart--report of two cases and review of the literature.

PMID- 22648080
TI  - Magnetic resonance imaging of inflammatory arthropathies of peripheral joints.
AB  - As the treatment of inflammatory arthropathies has advanced with new therapies
      that can slow or even halt the development of disabling disease, early and
      accurate diagnosis has become imperative. Magnetic resonance (MR) imaging has
      proved to be very sensitive in the detection of erosions, but more importantly,
      it can demonstrate pre-erosive changes. Detection of synovitis and edema-like
      bone marrow lesions for initial diagnosis and as an indicator of disease
      progression can provide crucial information leading to therapeutic interventions
      before permanent joint damage occurs. Understanding the characteristic intra
      articular and extra-articular MR imaging findings of the inflammatory arthritides
      allows the radiologist to provide appropriate consultations in the care of these
      patients. The MR appearances of both intra-articular and extra-articular findings
      of inflammatory arthritis are presented. Despite the advances in imaging,
      however, many of the MR findings remain nonspecific, and radiologists must avoid
      overdiagnosis by synthesizing all of the clinical information available into
      their interpretations.

PMID- 22648082
TI  - Cartilage magnetic resonance imaging techniques at 3 T: current status and future
      directions.
AB  - Magnetic resonance imaging (MRI) remains the imaging modality of choice for
      morphological and compositional evaluation of the articular cartilage. Accurate
      detection and characterization of cartilage lesions are necessary to guide the
      medical and surgical therapy and are also critical for longitudinal studies of
      the cartilage. Recent work using 3.0-T MRI systems shows promise in improving
      detection and characterization of the cartilage lesions, particularly with
      increasing use of high-resolution and high-contrast 3-dimensional sequences,
      which allow detailed morphological assessment of cartilage in arbitrary imaging
      planes. In addition, implementation of biochemical sequences in clinically
      feasible scan times has a potential in the early detection of cartilage lesions
      before they become morphologically apparent. This article discusses relative
      advantages and disadvantages of various commonly used as well as experimental MRI
      techniques to directly assess the morphology and indirectly evaluate the
      biochemical composition of the articular cartilage.

PMID- 22648083
TI  - Magnetic resonance imaging of spondyloarthritis: spine and SI joints.
AB  - Magnetic resonance imaging (MRI) has been recently introduced as a classification
      criterion for spondyloarthropathies in the Assessment of Spondylarthritis
      International Society criteria. Therefore, it plays an increasingly important
      role in the diagnostic workup of spondyloarthropathies. In this article, we will
      review the MRI imaging features of axial spondyloarthritis from sacroiliitis to
      spine abnormalities; we will explain the rationale for MRI imaging, the evidence
      for whole body MRI, and we will approach the use of MRI for monitoring treatment
      response.

PMID- 22648081
TI  - Molecular characterization of rheumatoid arthritis with magnetic resonance
      imaging.
AB  - Several recent advances in the field of magnetic resonance imaging (MRI) may
      transform the detection and monitoring of rheumatoid arthritis (RA). These
      advances depict both anatomic and molecular alterations from RA. Previous
      techniques could detect specific end products of metabolism in vitro or were
      limited to providing anatomic information. This review focuses on the novel
      molecular imaging techniques of hyperpolarized carbon-13 MRI, MRI with iron
      labeled probes, and fusion of MRI with positron emission tomography. These new
      imaging approaches go beyond the anatomic description of RA and lend new
      information into the status of this disease by giving molecular information.

PMID- 22648085
TI  - [Vitamin B12 and folic acid deficiency in the population over 65 years: a
      descriptive study].
AB  - INTRODUCTION: The aim of this study is to establish the prevalence of vitamin B12
      and folic acid deficiency in the population of 65 years and over in semi-urban
      and rural area, as well as investigating the risk factors, and the determining
      factors of this deficiency in this population and its relationship with the
      prevalence of concomitant cardiovascular and cognitive diseases. MATERIALS AND
      METHODS: A cross-sectrionall study conducted in the Geriatrics Outpatients in the
      period between 2008 and 2010. Demographic, clinical and laboratory were collected
      at 3 different times.A bivariate analysis was performed with lack of vitamin B12
      and folic acid, as the outcome variables. RESULTS: Vitamin B12 defieciency was
      found in 16.5% of the sample, and no folic acid deficiency. A strong association
      was found with vitamin B12 deficiency and cardiac and cerebrovascular diseases,
      vascular risk factors and drugs administered in prevention of cardiac events and
      ischaemic stroke. CONCLUSIONS: There was a higher prevalence of vitamin B12
      deficiency in the elderly population in the catchment area of Medina del Campo
      compared to that found in the literature, but not so with the isolated deficiency
      of folic acid.

PMID- 22648086
TI  - Genetics of atherosclerosis: the power of plaque burden and progression: invited
      commentary on Dong C, Beecham A, Wang L, Blanton SH, Rundek T, Sacco RL. Follow
      Up association study of linkage regions reveals multiple candidate genes for
      carotid plaque in Dominicans atherosclerosis 223 (1) (2012) 177-183.

PMID- 22648084
TI  - Binding of amelogenin to MMP-9 and their co-expression in developing mouse teeth.
AB  - Amelogenin is the most abundant matrix protein in enamel. Proper amelogenin
      processing by proteinases is necessary for its biological functions during
      amelogenesis. Matrix metalloproteinase 9 (MMP-9) is responsible for the turnover
      of matrix components. The relationship between MMP-9 and amelogenin during tooth
      development remains unknown. We tested the hypothesis that MMP-9 binds to
      amelogenin and they are co-expressed in ameloblasts during amelogenesis. We
      evaluated the distribution of both proteins in the mouse teeth using
      immunohistochemistry and confocal microscopy. At postnatal day 2, the spatial
      distribution of amelogenin and MMP-9 was co-localized in preameloblasts,
      secretory ameloblasts, enamel matrix and odontoblasts. At the late stages of
      mouse tooth development, expression patterns of amelogenin and MMP-9 were similar
      to that seen in postnatal day 2. Their co-expression was further confirmed by RT
      PCR, Western blot and enzymatic zymography analyses in enamel organ epithelial
      and odontoblast-like cells. Immunoprecipitation assay revealed that MMP-9 binds
      to amelogenin. The MMP-9 cleavage sites in amelogenin proteins across species
      were found using bio-informative software program. Analyses of these data suggest
      that MMP-9 may be involved in controlling amelogenin processing and enamel
      formation.

PMID- 22648087
TI  - The effect of acute administration of statins on coronary microcirculation during
      the pre-revascularization period in patients with myocardial infraction.
AB  - The beneficial effects of statin pretreatment as well as of staccato reperfusion
      (SR) on myocardium have been demonstrated in patients undergoing cardiac
      interventions. In this study, we compared the effects of the acute statin
      administration prior to percutaneous coronary intervention (PCI) with the effects
      of staccato or abrupt reperfusion on coronary microcirculation in patients with
      myocardial infarction (MI). METHODS: We randomly assigned 47 patients who had ST
      elevation or non-ST-elevation MI 48 h prior to PCI, into three groups: staccato
      reperfusion (consisting of 6 periods of 10-s balloon inflation/deflation) plus
      statin therapy (SRSG), statin therapy plus abrupt reperfusion (SG), and abrupt
      reperfusion alone (ARG). Myocardial contrast echocardiography (MCE) was performed
      to assess the blood volume (A), velocity (beta) and flow (A * beta) of the
      segments associated with the PCI-treated artery the day following intervention
      and 30 days after. LV end-diastolic (EDV) and systolic volumes (ESVs), wall
      motion score index (WMSI) were evaluated. RESULTS: Compared to ARG, SRSG and SG
      resulted in a greater improvement in A, beta and A * beta (F = 20.6, p < 0.001
      for A, F = 3.5, p = 0.03 for beta and F = 11.3, p < 0.001 for A * beta for the
      overall effect of intervention) as well as a greater decrease of WMSI, EDV and
      ESV (p < 0.01) one month post-PCI. The changes of all echocardiography markers
      were greater in SRSG than SG (p < 0.01). The % changes in ESV correlated with the
      corresponding % changes in MCE indices in SRSG and SG (p < 0.05). CONCLUSION: The
      acute statin administration prior to reperfusion either alone or in synergy with
      staccato reperfusion ameliorates coronary microcirculatory dysfunction in
      patients with myocardial infarction.

PMID- 22648088
TI  - Measuring what matters: effectively predicting language and literacy in children
      with cochlear implants.
AB  - OBJECTIVES: To evaluate how well various language measures typically used with
      very young children after they receive cochlear implants predict language and
      literacy skills as they enter school. METHODS: Subjects were 50 children who had
      just completed kindergarten and were 6 or 7 years of age. All had previously
      participated in a longitudinal study from 12 to 48 months of age. 27 children had
      severe-to-profound hearing loss and wore cochlear implants, 8 had moderate
      hearing loss and wore hearing aids, and 15 had normal hearing. A latent variable
      of language/literacy skill was constructed from scores on six kinds of measures:
      (1) language comprehension; (2) expressive vocabulary; (3) phonological
      awareness; (4) literacy; (5) narrative skill; and (6) processing speed. Five
      kinds of language measures obtained at six-month intervals from 12 to 48 months
      of age were used as predictor variables in correlational analyses: (1) language
      comprehension; (2) expressive vocabulary; (3) syntactic structure of productive
      speech; (4) form and (5) function of language used in language samples. RESULTS:
      Outcomes quantified how much variance in kindergarten language/literacy
      performance was explained by each predictor variable, at each earlier age of
      testing. Comprehension measures consistently predicted roughly 25-50 percent of
      the variance in kindergarten language/literacy performance, and were the only
      effective predictors before 24 months of age. Vocabulary and syntactic complexity
      were strong predictors after roughly 36 months of age. Amount of speech produced
      in language samples and number of answers to parental queries explained moderate
      amounts of variance in performance after 24 months of age. Number of manual
      gestures and nonspeech vocalizations produced in language samples explained
      little to no variance before 24 months of age, and after that were negatively
      correlated with kindergarten performance. The number of imitations produced in
      language samples at 24 months of age explained about 10 percent of variance in
      kindergarten performance, but was otherwise not correlated or negatively
      correlated with kindergarten outcomes. CONCLUSIONS: Before 24 months of age, the
      best predictor of later language success is language comprehension. In general,
      measures that index a child's cognitive processing of language are the most
      sensitive predictors of school-age language abilities.

PMID- 22648089
TI  - Transmyringeal ventilation tube treatment: a 10-year cohort study.
AB  - OBJECTIVE: This ten-year cohort study was intended to determine the incidence and
      expected outcome of ventilation tube treatment at a clinic that serves a
      community with 300,000 inhabitants. METHODS: All children aged 0-10 years, who
      received their first ventilation tube during 1996, were followed over 10 years,
      at the department of Otorhinolaryngology, county hospital Ryhov, Jonkoping,
      Sweden. All acute and planned visits were recorded and analyzed, but no extra
      visits were scheduled due to participation in the study. RESULTS: In 1996 the
      overall incidence of tube insertion in the age group 0-10 years was 1 percent. A
      total of 155 children were entered, and 146 (94 percent) fulfilled the study.
      During the 10 years' follow up, a total of 409 acute visits and 1485 planned
      visits were made. In approximately 50 percent of the cases the first ventilation
      tube was still in place after one year. Infection occurred in 53 percent of the
      treated ear(s) at least once; the risk for infection was higher if the indication
      for ventilation tube placement was recurrent acute otitis media. In 45 percent of
      the children at least one more tube insertion was needed. A permanent perforation
      after tube treatment was seen in 2 percent of the treated ears. After 5 years,
      one half of the children were declared free from middle ear disease, but at the
      termination of the study 17 percent of the children were still in need of regular
      visits to an otologist due to residual ear problems. CONCLUSION: This study shows
      the natural course of treatment with middle ear ventilation tubes in a cohort of
      children aged 0-10 years during a ten-year period. The incidence of ventilation
      tube treatment was 1 percent. It is evident that many children need a prolonged
      contact with an ear-nose and throat specialist when treated with a ventilation
      tube.

PMID- 22648093
TI  - Influence of lattice dynamics on charge transport in the dianthra[2,3-b:2',3'-f]
      thieno[3,2-b]thiophene organic crystals from a theoretical study.
AB  - The influence of lattice dynamics on carrier mobility has received much attention
      in organic crystalline semiconductors, because the molecular components are held
      together by weak interactions and the transfer integrals between neighboring
      molecular orbitals are extremely sensitive to small nuclear displacements.
      Recently, it has been shown that the dynamic disorder has little effect on hole
      mobility in the ab plane of pentacene, but a reasonable explanation is absent for
      such a puzzle. To better understand the effect of lattice vibrations on carrier
      transport, a further study is required for other organic materials. In this work,
      a mixed molecular dynamic and quantum-chemical methodology is used to assess the
      effect of nuclear dynamics on hole mobility in the dianthra[2,3-b:2',3'-f]
      thieno[3,2-b]thiophene (DATT) crystals which exhibit high air stability with the
      hole mobility as large as that in rubrene-based devices. It is found that the
      lattice vibrations lead to an increasing encumbrance for hole transport in the ab
      plane of the DATT crystals as the temperature increases. By comparing the crystal
      structures of DATT and pentacene, the reduced hole mobility in DATT is attributed
      to the unsymmetric arrays of nearest-neighboring molecular dimers in the ab
      plane, because the electronic coupling exhibits unbalanced thermal fluctuations
      for the nearest-neighboring dimers which then induces a stronger oscillation for
      carriers along the directions with asymmetric packing. To further relate the
      dynamic disorder with hole transport, the variations of anisotropic mobilities
      are also analyzed. As a result, the negligible effect of lattice dynamics on the
      hole mobility in pentacene is explained by the centrosymmetric molecular packing
      of the nearest-neighboring molecular pairs in the ab plane.

PMID- 22648092
TI  - Effects of pomegranate juice supplementation on pulse wave velocity and blood
      pressure in healthy young and middle-aged men and women.
AB  - Pomegranate juice may improve cardiovascular risk because of its content of
      antioxidant polyphenols. We conducted a randomized placebo-controlled parallel
      study to examine the effect of pomegranate juice on pulse wave velocity (PWV),
      blood pressure (BP) and plasma antioxidant status (ferric reducing power; FRAP)
      in 51 healthy adults (30-50 years). Participants consumed 330 ml/day of
      pomegranate juice or control drink for four weeks. Measurements were made at
      baseline and at four weeks. There was no effect of the intervention on PWV (P =
      0.694) and plasma FRAP (P = 0.700). However, there was a significant fall in
      systolic blood pressure (-3.14 mmHg, P < 0.001), diastolic blood pressure (-2.33
      mmHg P < 0.001) and mean arterial pressure (-2.60 mmHg, P < 0.001). Change in
      weight was similar in the two groups over the intervention period (P = 0.379).
      The fall in BP was not paralleled by changes in concentration of serum
      angiotensin converting enzyme. We conclude that pomegranate juice supplementation
      has benefits for BP in the short term, but has no effect on PWV. The mechanism
      for the effect is uncertain.

PMID- 22648094
TI  - Potential diagnostic utility of anti-centromere antibody in primary Sjogren's
      syndrome in the UK.

PMID- 22648095
TI  - Intravenous iron therapy is the option for RA patient with absolute iron
      deficiency accompanied with functional iron deficiency.

PMID- 22648096
TI  - Pure transvaginal laparoscopic appendectomy.
AB  - BACKGROUND: Natural orifice transluminal endoscopic surgery has been at the
      forefront of minimally invasive surgery. Benefits include no visible scars, less
      pain, and shorter recovery time. We describe a video of a 37-year-old female who
      underwent a pure transvaginal appendectomy (TVA) for acute appendicitis. This is
      1 of 18 successfully performed TVAs at Yale-New Haven Hospital. Appropriate
      Institutional Review Board was obtained preoperatively. METHODS: The patient was
      positioned in steep Trendelenburg and then a weighted speculum was introduced
      into the vagina allowing exposure of the posterior vaginal fornix. The cervix was
      grasped with a single-toothed tenaculum on the posterior cervical lip and the
      posterior vaginal fornix was visualized. Access to the peritoneum was achieved by
      electrocautery and then sharp dissection. A SILSTM port (Covidien, Mansfield, MA,
      USA) was introduced and pneumoperitoneum up to 15 mmHg was achieved. Two 5-mm
      trocars and one 12-mm trocar were used. A 5-mm 30 degrees  angled endoscope, a
      flexible reticulating endograsper, and straight standard instruments were used.
      The identified appendix was dissected and a stapler was used to divide the
      mesoappendix from the appendix. Following confirmation of good hemostasis and no
      spillage of bowel contents, the appendix was removed from the abdomen within a
      retrieval bag and the culdotomy was closed with a running absorbable suture. The
      patient tolerated the 27 min procedure well and was discharged home in good
      condition on postoperative day 1.

PMID- 22648097
TI  - Laparoscopic surgery for palliative resection of the primary tumor in incurable
      stage IV colorectal cancer.
AB  - BACKGROUND: The purpose of the study was to evaluate the feasibility and efficacy
      of laparoscopic palliative resection in patients with incurable stage IV
      colorectal cancer. METHODS: We reviewed 100 patients with incurable stage IV
      colorectal cancer who underwent palliative resection of the primary tumor between
      2002 and 2009 at National Cancer Center Hospital East (NCCHE). Outcomes and
      postoperative course were compared between patients who underwent open and
      laparoscopic surgery. RESULTS: Of the 100 patients, 22 were treated with a
      laparoscopic procedure and 78 underwent an open surgical procedure. There was no
      difference in the preoperative characteristics of the two groups. In the
      laparoscopic group, the mean operation time was significantly longer (177 vs. 148
      min, p = 0.007) and the amount of blood loss was significantly lower (166 vs. 361
      ml, p = 0.002). Postoperative complications occurred in 5 patients (22.7 %) after
      laparoscopic surgery and in 21 patients (26.9 %) after open surgery, with no
      significant difference between the two groups. Time to flatus, time to start of
      food intake, and hospital stay were all shorter after laparoscopic surgery (3.0
      vs. 3.8 days, p = 0.003; 3.6 vs. 5.0 days, p < 0.001; and 12.0 vs. 15.0 days, p =
      0.005; respectively). Significantly more patients in the laparoscopic group had
      >15 % lymphocytes on postoperative day 7 (p = 0.049). Overall survival rates were
      73.7 and 75.5 % at 1 year after laparoscopic surgery and open surgery,
      respectively (p = 0.344). CONCLUSIONS: A laparoscopic procedure should be
      considered for palliative resection of the primary tumor for incurable stage IV
      colorectal cancer, because the results of this study indicate that the procedure
      is safe and effective.

PMID- 22648098
TI  - Transoral incisionless fundoplication for treatment of gastroesophageal reflux
      disease in clinical practice.
AB  - BACKGROUND: Transoral incisionless fundoplication is a recently introduced
      endoluminal technique for the treatment of gastroesophageal reflux disease
      (GERD). The objective of this study was to determine outcomes in chronic GERD
      patients who were referred for surgical management. METHODS: A cohort of 38
      patients underwent transoral incisionless fundoplication (TIF) in a tertiary care
      setting. Pre- and post-procedure assessment included GERD-related quality of life
      questionnaires, proton pump inhibitor (PPI) usage, 24-h pH measurements, upper
      gastrointestinal endoscopy, esophageal manometry, and registration of adverse
      events. Duration of follow-up was 36 months. RESULTS: Gastroesophageal valves
      were constructed of 4 cm (range, 4-6) in length and 220 degrees  (range, 180-240)
      in circumference. One serious adverse event occurred, consisting of intraluminal
      bleeding at a fastener site. Hiatal hernia was completely reduced in 56 % and
      esophagitis was cured in 47 % of patients. Postprocedure esophageal acid exposure
      did not significantly improve (p > 0.05). At 36 (range, 29-41) months follow-up
      14 patients (36 %) had undergone revisional laparoscopic fundoplication. Quality
      of life scores of the remaining cohort showed significant improvement (p <
      0.0001) and daily use of antisecretory medication was discontinued by 74 %.
      CONCLUSIONS: Endoluminal fundoplication improved quality of life and reduced the
      need for PPIs in only a subgroup of patients at 3 years follow-up. The amount of
      patients requiring additional medication and revisional surgery was high.

PMID- 22648099
TI  - Novel endoscopic delivery modality of infrared coagulation therapy for internal
      hemorrhoids.
AB  - BACKGROUND: A novel endoscopic delivery system for infrared coagulation therapy
      (IRC) has been designed recently. IRC is a well-established treatment for
      symptomatic internal hemorrhoids. Patients frequently undergo lower endoscopy
      before hemorrhoid treatment to eliminate other sources of bleeding. Current
      treatment options are difficult to perform without an anal retractor, adequate
      lighting, and specialized instruments. Endoscopic IRC is an attractive
      alternative to standard IRC, because it can be performed during the lower
      endoscopy. TECHNIQUE: Endoscopic IRC utilizes infrared radiation generated by a
      control box, which is applied to the tissue through a flexible, fiber optic light
      guide (Precision Endoscopic Infrared CoagulatorTM). The light guide is placed
      through the colonoscope or flexible sigmoidoscope in the same chamber as other
      endoscopic instruments. METHODS: A retrospective review was performed using a
      prospectively collected database. A standardized protocol was utilized in all
      patients. Patients graded their symptoms before and after therapy by using the
      visual analog symptom severity scoring system (range, 0-10). These results were
      analyzed by using the nonparametric Wilcoxon signed-rank test. Exact P values
      were computed by using the R function wilcox.exact. RESULTS: A total of 55
      patients underwent endoscopic IRC for predominately grade II and grade III
      symptomatic internal hemorrhoids (71 %). There were 22 (40 %) female patients.
      Posttherapy results indicated a significant improvement in global symptoms
      (pretreatment average global score = 2.24 vs. posttreatment average global score
      = 0.28; P < 0.0001). There have been no adverse events reported to date.
      CONCLUSIONS: Endoscopic IRC provides improved visibility and efficiency, allowing
      simultaneous treatment of symptomatic internal hemorrhoids at the time of lower
      endoscopy. Patients experienced significant improvement in their symptoms after a
      single session of endoscopic IRC. There are a variety of additional endoscopic
      IRC therapeutic utilities: endoscopic management of angiodysplasia, inflammation,
      hemostasis, and NOTES applications.

PMID- 22648100
TI  - A randomized crossover trial examining low- versus high-fidelity simulation in
      basic laparoscopic skills training.
AB  - BACKGROUND: Previous randomized studies have compared high- versus low-fidelity
      laparoscopic simulators; however, no proficiency criteria were defined and
      results have been mixed. The purpose of this research was to determine whether
      there were any differences in the learning outcomes of participants who had
      trained to proficiency on low- or high-fidelity laparoscopic surgical simulators.
      METHODS: We conducted a randomized, prospective crossover trial with participants
      recruited from New South Wales, Western Australia, and South Australia.
      Participants were randomized to high-fidelity (LapSim, Surgical Science) or low
      fidelity (FLS, SAGES) laparoscopic simulators and trained to proficiency in a
      defined number of tasks. They then crossed over to the other fidelity simulator
      and were tested. The outcomes of interest were the crossover mean scores, the
      proportion of tasks passed, and percentage passes for the crossover simulator
      tasks. RESULTS: Of the 228 participants recruited, 100 were randomized to LapSim
      and 128 to FLS. Mean crossover score increased from baseline for both simulators,
      but there was no significant difference between them (11.0 % vs. 11.9 %). FLS
      trained participants passed a significantly higher proportion of crossover tasks
      compared with LapSim-trained participants (0.26 vs. 0.20, p = 0.016). A
      significantly higher percentage of FLS-trained participants passed intracorporeal
      knot tying than LapSim-trained participants (35 % vs. 8 %, p < 0.001).
      CONCLUSION: Similar increases in participant score from baseline illustrate that
      training on either simulator type is beneficial. However, FLS-trained
      participants demonstrated a greater ability to translate their skills to
      successfully complete LapSim tasks. The ability of FLS-trained participants to
      transfer their skills to new settings suggests the benefit of this simulator type
      compared with the LapSim.

PMID- 22648101
TI  - The effect of simulation in improving students' performance in laparoscopic
      surgery: a meta-analysis.
AB  - BACKGROUND: There is increasing interest in using simulators for laparoscopic
      surgery training, and simulators have rapidly become an integral part of surgical
      education. METHODS: We searched MEDLINE, EMBASE, Cochrane Library, and Google
      Scholar for randomized controlled studies that compared the use of different
      types of simulators. The inclusion criteria were peer-reviewed published
      randomized clinical trials that compared simulators versus standard
      apprenticeship surgical training of surgical trainees with little or no prior
      laparoscopic experience. Of the 551 relevant studies found, 17 trials fulfilled
      all inclusion criteria. The effect sizes (ES) with 95 % confidence intervals [CI]
      were calculated for multiple psychometric skill outcome measures. RESULTS: Data
      were combined by means of both fixed- and random-effects models. Meta-analytic
      combined effect size estimates showed that novice students who trained on
      simulators were superior in their performance and skill scores (d = 1.98, 95 %
      CI: 1.20-2.77; P < 0.01), were more careful in handling various body tissue (d =
      1.08, 95 % CI: 0.36-1.80; P < 0.01), and had a higher accuracy score in
      conducting laparoscopic tasks (d = 1.38, 95 % CI: 0.30-2.47; P < 0.05).
      CONCLUSION: Simulators have been shown to provide better laparoscopic surgery
      skills training for trainees than the traditional standard apprenticeship
      approach to skill development. Surgical residency programs are highly encouraged
      to adopt the use of simulators in teaching laparoscopic surgery skills to novice
      students.

PMID- 22648102
TI  - Hiatal hernia, Barrett's esophagus, and long-term symptom control after
      laparoscopic fundoplication for gastroesophageal reflux.
AB  - BACKGROUND: The aim of this study was to determine the long-term symptom control
      after laparoscopic fundoplication for gastroesophageal reflux disease (GERD), and
      possible prognostic factors. METHODS: A cohort of 271 patients, operated on at a
      university hospital from 1996 through 2002, was eligible for evaluation after a
      median interval of 102 months (range = 12-158). The time between surgery and
      recurrence of reflux symptoms (i.e., time to treatment failure) served as the end
      point for statistical analysis. Putative risk factors for symptom recurrence were
      analyzed by univariate analysis and by using Cox's multiple-hazards regression.
      RESULTS: According to Kaplan-Meier estimates, the rate of reflux symptom
      recurrence was 15 % after 108 months, 11 % in cases without intestinal
      metaplasia, but 43 % in patients with long-segment (>= 3 cm) Barrett's esophagus
      (BE; p < 0.0001). Reflux symptoms recurred in 22 % of cases with a hiatal hernia
      (HH) >= 3 cm before operation, but only in 7 % with smaller or absent HH (p =
      0.005). Multivariate analysis revealed a relative risk of 6.6 (CI = 3.0-13.0) for
      long-segment BE and 3.0 (CI = 1.7-10.1) for HH >= 3 cm. A strong statistical
      interaction was found between HH >= 3 cm and long-segment BE: the small group (n
      = 18) of cases exhibiting both risk factors had an exaggerated recurrence rate of
      72 % at 108 months. CONCLUSIONS: Laparoscopic fundoplication for symptomatic GERD
      provided a long-lasting abolition of reflux symptoms in 231 of 271 (85 %)
      patients. HH >= 3 cm and long-segment BE were shown as independent prognostic
      factors favoring recurrence.

PMID- 22648103
TI  - Radical resection of gallbladder cancer: could it be robotic?
AB  - BACKGROUND: The only potentially curative option for patients with gallbladder
      cancer is radical resection. This is the first report that describes the
      successful application of a minimally invasive, robot-assisted radical resection,
      including lymphadenectomy, in five gallbladder cancer patients. METHODS: Medical
      records of patients who underwent radical resection of gallbladder cancer via the
      da Vinci robotic surgical system in the Hepato-Bilio-Pancreatic Surgical
      Department of the Shanghai Ruijin Hospital, China, between March 2010 and July
      2011 were reviewed and analyzed. RESULTS: Robot-assisted radical resection was
      successful in all five patients. The mean number of excised lymph nodes was 9
      (range = 3-11), mean operative time was 200 min (range = 120-300 min), mean
      intraoperative blood loss was 210 ml (range = 50-400 ml), and mean length of
      hospital stay was 7.4 days (range = 7-8 days). All patients were discharged with
      no reported complications. Mean postoperative follow-up was 11 months (range = 1
      17 months). One patient died due to tumor recurrence 10 months postsurgically,
      but there was no recurrence in the remaining four patients during the follow-up
      period. CONCLUSIONS: Robot-assisted radical resection for gallbladder cancer is
      both feasible and safe. Compared to laparoscopic surgery, the robotic surgery
      system is better suited for subtle dissection in a narrow, deep space. This is
      advantageous for both the removal of lymph nodes near the pancreas and
      hepatoduodenal ligament and the skeletonization of the hepatoduodenal ligament,
      the hepatic artery, and the celiac axis. The long-term outcome and direct
      comparisons to laparotomy in a larger patient cohort are needed to provide more
      clinical data supporting the superiority of this approach.

PMID- 22648104
TI  - Systematic review of validity testing in colonoscopy simulation.
AB  - BACKGROUND: Simulation is a useful adjunct to skills-based training. It
      potentially avoids risk to patients during training and development of basic
      interventional techniques. This may be of particular relevance in colonoscopy
      where the learning curve can be long. Several endoscopic devices exist that
      simulate colonoscopy for training purposes. This study was designed to review the
      evidence for the validity of these simulators. METHODS: MEDLINE (1947 to
      present), PubMed, Embase classic + Embase, the metaRegister of Controlled Trials,
      and the Education Resources Information Center (ERIC) were searched for studies
      validating colonoscopy simulators. For each study, we recorded the type of
      simulator used, the tasks assessed, the endpoints reported, and the type of
      validity measured. Common endpoints between studies were compared, and the
      evidence was graded. RESULTS: Thirteen studies met the inclusion criteria.
      Construct validity was reported in five (41.7 %) studies for the Accutouch HT
      Immersion (cases 1, 3, and 4), four studies (33.3 %) for the GI mentor II
      (Simbionix) (Modules 1.1, 1.3, 1.7, 2.1, and 5), two studies (16.7 %) for the
      Olympus Endo Ts-1 2nd Generation, and one study for the Endo X bovine model. Face
      validity was reported for the Accutouch HT Immersion, the Olympus 2nd Generation,
      and the KAIST-Ewha. Content validity was reported for the all simulators,
      excluding the KAIST-Ewha. The only report of criterion validity was for the Endo
      X bovine model. CONCLUSION: Evidence exists to support the face, content, and
      construct validity of several virtual reality colonoscopy simulators for specific
      diagnostic and therapeutic modules with selected endpoints. One study
      demonstrates content, construct, and criterion validity for an ex vivo animal
      platform. Further work is needed to demonstrate the criterion validity of all
      devices.

PMID- 22648105
TI  - A comparative study of the surgical outcomes of robotic and conventional open
      modified radical neck dissection for papillary thyroid carcinoma with lateral
      neck node metastasis.
AB  - BACKGROUND: Several endoscopic modified radical neck dissections (MRND) have been
      conducted since the introduction of the endoscopic technique to thyroid surgery
      with the aim of avoiding a long cervical scar. Furthermore, the recent
      introduction of surgical robotic systems has increased the precision of
      endoscopic techniques. The aim of this study was to evaluate and compare the
      early surgical outcomes of robotic and conventional open MRND for papillary
      thyroid carcinoma (PTC) with lateral neck node metastasis (LNM). METHODS: From
      January 2009 to May 2010, 165 patients with PTC underwent bilateral total
      thyroidectomy with central compartment neck dissection and ipsilateral MRND. Of
      these patients, 56 formed the robotic procedure group (RG) and 109 the
      conventional open procedure group. These two groups were retrospectively compared
      with respect to their clinicopathological characteristics, early surgical
      outcomes, and surgical completeness. RESULTS: The operative time was longer, mean
      tumor size was smaller, mean age was lower, and disease stage was earlier in the
      RG. However, mean numbers of retrieved lymph nodes were similar in the two
      groups, and mean hospital stay after surgery was shorter in the RG. Furthermore,
      complication rates were similar in the two groups, and there was no statistical
      difference in postoperative Tg levels between the groups. CONCLUSIONS: Robotic
      MRND was found to be similar to conventional open MRND in terms of early surgical
      outcomes and surgical completeness but leaves no scar on the neck area. Robotic
      MRND can be viewed as an acceptable alternative method in low-risk PTC with LNM.

PMID- 22648106
TI  - The risk of postpolypectomy bleeding during colonoscopy in patients with early
      liver cirrhosis.
AB  - BACKGROUND: Colonoscopists are often hesitant to perform endoscopic polypectomy
      in patients with liver cirrhosis (LC) because of the risk for postpolypectomy
      bleeding (PPB). However, little is known about the risk of PPB in these patients.
      METHODS: We performed a retrospective study of patients with early LC who
      underwent colonoscopic polypectomy at a single center between September 2006 and
      May 2011. We investigated the incidence of immediate PPB (IPPB) and delayed PPB
      (DPPB) in these patients. In addition, we investigated which LC-related and polyp
      related factors were associated with IPPB. RESULTS: Thirty patients with LC were
      included in our study, and 29 (96.7 %) of them were classified in Child-Pugh
      class A or B. The mean prothrombin time was 1.27 +/- 0.23, and the mean platelet
      count was 136.77 +/- 106.49 * 10(3)/L. A total of 66 polyps in 30 patients were
      removed. In terms of IPPB, only 2 (3.03 %) of the 66 removed polyps presented
      with mild oozing and were controlled by hemostatic procedures using hemoclips.
      DPPB did not occur in any of the patients in the IPPB or the non-IPPB group.
      Although the IPPB polyp group was too small to detect statistical significance,
      the IPPB polyps were larger than the non-IPPB polyps (22.5 +/- 10.61 vs. 7.22 +/-
      3.01 mm), and the gross morphology of both IPPB polyps was the pedunculated type.
      However, LC-related variables such as platelet counts and Child-Pugh scores did
      not significantly differ between the IPPB and non-IPPB groups. CONCLUSIONS: In
      patients with early LC, the risk of postpolypectomy bleeding was acceptably low
      and there was no case with DPPB. Therefore, polypectomy can be performed with
      caution. IPPB was associated with the size and the gross morphology of the
      polyps. However, LC-related variables in patients with early LC did not impact
      IPPB.

PMID- 22648107
TI  - Survival and surgical outcomes after laparoscopy-assisted total gastrectomy for
      gastric cancer: case-control study.
AB  - BACKGROUND: Few results regarding the long-term survival from laparoscopy
      assisted total gastrectomy (LATG) have been reported. The purpose of this study
      was to investigate the feasibility of LATG in terms of long-term survival and
      morbidity. METHODS: A case-control study was conducted on 100 cases of LATG and
      348 cases of open total gastrectomy (OTG) performed for treating clinical stage I
      (cT1N0, cT1N1, and cT2N0) gastric cancer from August 2003 to December 2008 at the
      National Cancer Center of Korea. The clinicopathological characteristics,
      surgical outcomes, and complications were compared between the LATG and OTG
      groups. The overall survival rate and disease-free survival rate were analyzed
      using a Cox proportional hazards model for multivariate analysis. RESULTS: The
      rate of postoperative complications was 27 %, the most common being anastomotic
      stenosis from LATG (9 %). There were no significant differences in surgical
      outcomes and complications between the LATG and OTG groups except for a longer
      operating time for LATG. Survival rates were also similar between groups; the
      hazard ratio of LATG versus OTG was 0.43 (95 % confidence interval [CI] = 0.15
      1.20; p = 0.107) for overall survival and 0.47 (95 % CI = 0.19-1.18; p = 0.106)
      for disease-free survival. CONCLUSION: LATG may be a feasible procedure with
      acceptable complications and long-term survival rate for clinical stage I gastric
      cancer.

PMID- 22648108
TI  - Differences in biomechanical stability using various fibrin glue compositions for
      mesh fixation in endoscopic inguinal hernia repair.
AB  - BACKGROUND: In hernia surgery, mesh fixation with fibrin glue instead of tacks
      and sutures can demonstrably reduce postoperative morbidity without increasing
      recurrence rates. In some cases there are significant differences in the
      biomechanical properties, depending on the functional structure of the meshes.
      Furthermore, there are various fibrin glue products on the market and these are
      used for mesh fixation. This study compared the fixation strength of fibrin glues
      in combination with various meshes. METHODS: Three different lightweight
      polypropylene meshes (TiMESHTM light, ULTRAPROTM, Optilene((r)) LP) were tested.
      All meshes were fixed using 2 ml of each of the three different fibrin glues
      (TISSUCOL((r)), QUIXIL((r)), EVICEL((r))) and tested for their biomechanical
      stability. The defect in the muscle tissue used was 45 mm for a mesh size of 10 *
      15 cm. Measurements were conducted using a standardized stamp penetration test,
      while aiming not to use a fixation strength of less than 32 N. RESULTS: With
      TISSUCOL, the fixation of Optilene LP proved to be significantly better than that
      of TiMESH or ULTRAPRO (97.3 vs. 47.9 vs. 34.9 N, p < 0.001). With EVICEL, it was
      possible to also achieve good tissue fixation for the ULTRAPRO mesh, while the
      results obtained for Optilene and TiMESH were relatively poorer [114.7 vs. 92.4 N
      (p = 0.056), vs. 64.3 N (p < 0.001)]. With QUIXIL, satisfactory results were
      obtained only for Optilene LP (43.6 N). CONCLUSION: This study showed that there
      were significant differences in the fixation strength of different polypropylene
      meshes in combination with various fibrin glues. Experiments demonstrated that
      for each mesh there is an optimum combination with a particular fibrin glue with
      respect to the fixation strength. It must now be verified whether these results
      can be extrapolated to clinical practice.

PMID- 22648109
TI  - Normokinetic biliary dyskinesia: a novel diagnosis.
AB  - BACKGROUND: Biliary dyskinesia diagnosed with CCK-HIDA scan and ejection fraction
      less than 35 % has been successfully treated by laparoscopic cholecystectomy.
      However, a population of patients with symptomatic biliary pain and a normal CCK
      HIDA scan never receive a diagnosis, and thus no definitive treatment. Some of
      these patients report a reproducible pain during their CCK-HIDA scan. It is
      hypothesized that these patients have a novel diagnosis, normokinetic biliary
      dyskinesia, and may have resolution of pain when treated with cholecystectomy.
      METHODS: A retrospective chart review was completed looking for patients with
      biliary pain in accordance with the ROME III criteria. Additional inclusion
      criteria were (1) greater than age 18 years, (2) reproducible biliary symptoms
      during the CCK-HIDA scan, and (3) an ejection fraction greater than 35 %.
      Treatment modality was laparoscopic cholecystectomy. Descriptive statistics were
      preformed, and data were reported as mean +/- standard deviation and range.
      RESULTS: Nineteen patients met the inclusion criteria for this study from August
      2008 to July 2011. There were 15 women and 4 men with a mean age of 48.4 +/- 13.0
      years. The mean ejection fraction was 75.1 +/- 19.4 %. The average duration of
      preoperative symptoms was 6.8 +/- 5.9 months and postoperative follow-up was 21.8
      +/- 10.6 months. Seventeen patients had complete resolution of symptoms, one had
      partial resolution, and one had no change. There was a complete resolution rate
      of 89.5 % and an improvement rate of 94.7 %. CONCLUSIONS: We suggest that
      patients who present with biliary pain, a normal CCK-HIDA scan with an ejection
      fraction greater than 35 %, and with reproducible symptoms on infusion of CCK
      could have a novel diagnosis: normokinetic biliary dyskinesia. Currently, these
      patients are excluded from the diagnosis of biliary dyskinesia and thus
      treatment. We hypothesize a potential new diagnosis, suggest cholecystectomy as
      treatment, and recommend a prospective study design for further evaluation.

PMID- 22648110
TI  - Clinical outcomes of patients who experienced perforation associated with
      endoscopic retrograde cholangiopancreatography.
AB  - BACKGROUND: Perforation after endoscopic retrograde cholangiopancreatography
      (ERCP) is a rare but severe complication. The purpose of this study was to assess
      the clinical outcomes with perforations after ERCP from a large number of cases.
      METHODS: Among 11,048 patients who underwent ERCP during 10 years, medical
      records from 68 patients (0.62 %) who experienced post-ERCP perforation with
      radiologic, endoscopic, or surgical evidence were retrospectively reviewed. We
      assessed the clinical outcomes of patients and analyzed the factors associated
      with poor outcomes, which were defined as mortality, prolonged hospital stay due
      to complications, or loss of chance of cure in the case of cancer. RESULTS:
      Twenty-nine patients were male, and the median age was 65.0 years. Therapeutic
      ERCP was performed in 52 cases (77 %). Common mechanisms of perforation were
      endoscopic sphincterotomy (37 %), catheter or guidewire (34 %), and endoscope (19
      %). In contrast to 9 patients who underwent emergent operation, 59 patients (87
      %) were conservatively treated. In 44 patients, perforation was detected during
      the procedure; however, detection after 24 h or permitted oral intake before
      detection occurred in 18 cases (27 %). Although 58 patients recovered without
      poor outcomes, 10 patients (15 %) experienced poor outcomes, which consisted of
      mortality (n = 4), loss of chance of cure (n = 2), and prolonged hospital stay
      without surgery more than 1 month due to complications (n = 4). By multiple
      logistic regression analysis, perforation by endoscope and rebound tenderness was
      statistically associated with poor outcomes (odds ratio: 13.7 and 7.3,
      respectively). CONCLUSIONS: Most patients fully recovered from perforation;
      however, some patients experienced grave outcomes, including mortality.
      Perforation by endoscope and rebound tenderness was significantly associated with
      poor outcomes.

PMID- 22648111
TI  - Can early laparoscopic cholecystectomy be the optimal management of cholecystitis
      with gallbladder perforation? A single institute experience of 74 cases.
AB  - BACKGROUND: Gallbladder perforation is a rare but serious complication of
      cholecystitis. It was usually managed by percutaneous gallbladder drainage
      (PTGBD) followed by elective cholecystectomy. However, evidences are emerging
      that early laparoscopic cholecystectomy (LC) is still feasible under these
      conditions. We hypothesized that early LC may have comparable surgical results as
      to those of PTGBD + elective LC. MATERIAL AND METHODS: From January 2005 to
      October 2011, patients admitted to China Medical University Hospital with a
      diagnosis of perforated cholecystitis were retrospectively reviewed. The
      diagnosis of gallbladder perforation was made by image and/or intraoperative
      findings. Those patients who had unstable hemodynamics that were not fitted for
      general anesthesia or those who had concomitant major operations were excluded.
      Patients were divided into three groups: early open cholecystectomy (group 1),
      early LC (group 2), and PTGBD followed by elective LC (group 3). The demographic
      features, surgical results, and patient outcome were analyzed and compared
      between groups. RESULTS: A total of 74 patients were included. All patients had
      similar demographic features except that patients in group 2 were younger (62 vs.
      72 and 73.5 years) compared with group 1 and group 3 (p = 0.016). There were no
      differences in terms of operative time, blood loss, conversion, and complication
      rate between three groups. The length of hospital stay (LOS) was significant
      shorter in group 2 patients compared with that of groups 1 and 3. CONCLUSIONS:
      Although PTGBD followed by elective LC was still the mainstay for the treatment
      of gallbladder perforation, early LC had comparable surgical outcomes as that of
      PTGBD + LC but with a significantly shorter LOS. Early LC should be considered
      the optimal treatment for gallbladder perforation, and PTGBD + LC can be
      preserved for those who carried a high risk of operation.

PMID- 22648112
TI  - Laparoscopic sleeve gastrectomy in adult and pediatric obese patients: a
      comparative study.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a recent bariatric procedure
      that has gained widespread popularity in morbidly obese adults. However,
      pediatric bariatric surgery is controversial, and the type(s) of bariatric
      surgery that are suitable for children and adolescents is under debate. No
      studies exit that compare LSG outcomes in adult and pediatric patients. We
      reviewed our experience to assess the safety, efficacy, and complications of LSG
      in adult and pediatric morbidly obese patients. METHODS: A retrospective review
      of all patients who underwent LSG by a single surgeon between March 2008 and
      February 2011 was performed. The 222 patients included 108 pediatric patients
      aged 21 years or younger and 114 adult patients older than 21 years. Baseline,
      operative, perioperative, and available follow-up data were abstracted. RESULTS:
      Pediatric patients had a mean age of 13.9 +/- 4.3 years and a mean baseline body
      mass index (BMI) of 49.6 kg/m(2), whereas adults had a mean age of 32.2 +/- 9.4
      years and a mean baseline BMI of 48.3 kg/m(2). Our pediatric group achieved a
      mean percent of excess weight loss (%EWL) of 32.4, 52.1, 65.8, and 64.9 % at 3,
      6, 12, and 24 months postoperative, respectively, compared with a mean %EWL of
      30.9, 55.2, 68.5, and 69.7 %, respectively, in our adult group (p > 0.05). During
      the 24-month follow-up period, pediatric patients attended 71.7 % of follow-up
      visits, whereas adults attended 61.2 % of follow-up visits (p = 0.01).
      Postoperative complications occurred in six (5.6 %) and eight (7 %) pediatric and
      adult patients, respectively. CONCLUSIONS: Laparoscopic sleeve gastrectomy in the
      pediatric age group is of similar safety and effectiveness compared with adults.
      Pediatric patients had fewer major complications and were more compliant with
      follow-up than adults. Nevertheless, long-term results are required to further
      clarify the safety and effectiveness of LSG in pediatric patients.

PMID- 22648113
TI  - Percutaneous endoscopic gastrostomy (PEG) with T-fasteners obviates the need for
      emergent replacement after early tube dislodgement.
AB  - BACKGROUND: Despite technical refinements of percutaneous endoscopic gastrostomy
      (PEG) tube placement, complications such as early tube dislodgement remain
      relatively static. This study aimed to review the experience of a high-volume
      endoscopy center after the introduction of T-fastener placement in high-risk
      patients. METHODS: The authors retrospectively reviewed PEG placement from
      October 2010 to September 2011, when their group began to use T-fasteners
      selectively in high-risk patients. Patients deemed to have an increased risk for
      early tube dislodgement underwent T-fastener placement at the time of PEG
      placement. Patients with PEG alone were compared with patients who had PEG with T
      fastener (PEG-T) placement. Statistical analysis was performed using SPSS version
      18. RESULTS: During the study period, 195 patients underwent PEG placement. For
      121 patients, PEG alone was performed, whereas PEG-T was performed for 74
      patients. Six patients had tube dislodgement (five early, one late) in the PEG-T
      cohort versus none in the PEG-alone cohort (P = 0.003). The first patient
      underwent diagnostic laparoscopy with replacement gastrostomy 2 days after tube
      dislodgement and was noted to have no contamination, with direct apposition of
      the stomach to the abdominal wall from the T-fasteners. The subsequent four
      patients with early tube dislodgement underwent non-emergent PEG replacement in
      the endoscopy unit within 24 h after tube dislodgement. In the short-term follow
      up period, no repeat dislodgements were noted. Early mortality in the entire
      cohort was experienced by 38 (19.5%) of the 195 patients. CONCLUSION: Placement
      of T-fasteners in high-risk patients may decrease overall morbidity if early tube
      dislodgement occurs. The findings show the safety of non-emergent endoscopic
      replacement of PEGs in certain patients. Early tube dislodgement may be a marker
      of overall mortality.

PMID- 22648114
TI  - Long-term postoperative outcomes of hypersplenism: laparoscopic versus open
      splenectomy secondary to liver cirrhosis.
AB  - BACKGROUND: Hypersplenism is a common clinical manifestation in patients with
      liver cirrhosis. For treatment, surgeons can choose between two options: open
      splenectomy (OS) or laparoscopic splenectomy (LS). Although splenectomy has wide
      exposure and acceptance as a remedy for the patients with hypersplenism secondary
      to liver cirrhosis, the data are sparse with regard to its long-term outcomes,
      including hematologic response and liver function after the surgery. This study
      aimed to determine the long-term effect of OS versus LS for cirrhotic patients
      with hypersplenism. METHODS: Between September 2003 and June 2011, the study
      enrolled 63 consecutive patients with hypersplenism secondary to liver cirrhosis
      who were treated with LS (n = 34) or OS (n = 29). The hematologic parameters and
      liver function in both groups were evaluated before and after splenectomy, and a
      comparative study of the long-term follow-up period was conducted. RESULTS:
      Postoperatively, 100% of the patients in both groups had a complete response in
      terms of platelet and leukocyte counts. No changes in liver function were noted.
      The LS group benefited from less intraoperative blood loss and a shorter
      postoperative hospital stay than the OS group experienced. The mean follow-up
      period was 25 months. To date, no death has been reported in either group. All
      the patients showed complete or partial hematologic response to splenectomy and
      exhibited improvement in liver function. None of the parameters differed
      significantly between the two groups. Portal or splenic vein thromboses were
      detected in three patients (2 in OS and 1 in LS), whereas esophageal variceal
      bleeding occurred for one patient in the LS group and one patient in the OS
      group. CONCLUSION: This study investigated patients with hypersplenism secondary
      to liver cirrhosis. The findings showed that LS can be considered a well-disposed
      surgical procedure with good surgical outcomes compared with OS.

PMID- 22648115
TI  - The value of multiple rapid swallows during preoperative esophageal manometry
      before laparoscopic antireflux surgery.
AB  - BACKGROUND: When multiple swallows are rapidly administered, esophageal
      peristalsis is inhibited, and pronounced lower esophageal sphincter relaxation
      ensues. After the last swallow of the series, a robust contraction sequence
      results. The authors hypothesize that multiple rapid swallows (MRS) may have
      value in predicting esophageal transit symptoms in patients undergoing
      laparoscopic antireflux surgery (LARS). METHODS: Records of patients undergoing
      esophageal high-resolution manometry (HRM) before LARS were evaluated. The
      evaluation of MRS included adequate inhibitory response during swallows and the
      contraction pattern after MRS. Dysphagia was scored based on a product of symptom
      frequency and severity using 5-point Likert scales. A composite dysphagia score
      comprised the sum of scores for solid and liquid dysphagia, and a score of 4 or
      higher was considered clinically significant. The normal and abnormal MRS
      responses of patients with preoperative, early, and late postoperative dysphagia
      were compared with those of patients with no dysphagia. RESULTS: In this study,
      63 patients (mean age, 60.3 +/- 1.7 years, 48 women) undergoing HRM before LARS
      successfully performed MRS (median, 5 swallows; longest interval between
      swallows, 3.2 +/- 0.1 s). After MRS, 14 patients (22.2%) had an intact
      peristaltic sequence. Complete failure of peristalsis was seen in 21 (33.3%), and
      incomplete esophageal inhibition in 25 (39.7%) of the remaining patients. When
      stratified by presence or absence of dysphagia, 58.3% of the subjects without
      dysphagia had a normal MRS response, whereas 83.3% had formation of peristaltic
      segments after MRS. In contrast, only 14% of the subjects with dysphagia had a
      normal MRS response (p <= 0.003 vs. the subjects with no dysphagia). Abnormal MRS
      responses were more prevalent in the patients with any preoperative and late
      postoperative dysphagia (p = 0.04 across groups) and in those with clinically
      significant dysphagia (p = 0.08 across groups). CONCLUSIONS: High-resolution
      manometry with MRS helps to predict dysphagia in subjects undergoing preoperative
      esophageal function testing before LARS.

PMID- 22648116
TI  - Tests of correlation between immediate postoperative gastroduodenal transit times
      and weight loss after laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: Previous studies have shown accelerated gastric emptying after sleeve
      gastrectomy. This study aimed to determine whether a correlation exists between
      immediate postoperative gastroduodenal transit time and weight loss after
      laparoscopic sleeve gastrectomy (LSG). Specifically, correlation tests were
      conducted to determine whether more rapid transit after LSG correlated with
      increased weight loss. METHODS: Data were collected from an institutional review
      board-approved electronic registry. All LSGs were performed over a 40-Fr bougie,
      starting 5 to 7 cm proximal to the pylorus. Gastroduodenal transit time (antrum
      to duodenum) was calculated from a postoperative day 1 esophagram. Pearson's
      correlation coefficient was used for statistical analysis. RESULTS: The analysis
      included 62 consecutive LSG patients. The mean gastroduodenal transit time was
      12.3 +/- 19.8 s. Almost all the patients (99%) had a transit time less than 60 s.
      The mean percentage of excess weight loss (%EWL) was 23.8 +/- 9.8% at 3 months,
      37.9 +/- 11.8% at 6 months, and 52.2 +/- 10.8% at 12 months. No correlation was
      found between gastroduodenal transit time and %EWL at 3, 6, or 12 months.
      CONCLUSION: No correlation was found between gastroduodenal transit time and
      weight loss after LSG.

PMID- 22648118
TI  - Magnetically anchored camera and percutaneous instruments maintain triangulation
      and improve cosmesis compared with single-site and conventional laparoscopic
      cholecystectomy.
AB  - BACKGROUND: This study evaluated operative outcomes and ergonomics for a magnetic
      camera (MAGS) used in conjunction with percutaneous instruments [percutaneous
      surgical set (PSS)] compared with single-site laparoscopic (SSL) and conventional
      laparoscopic (LAP) cholecystectomy techniques. METHODS: Four surgical trainees
      each performed three porcine cholecystectomies using three randomized techniques
      including MAGS/PSS, SSL, and LAP. The operative outcomes, procedure-specific
      ratings (1-5 scale; 1 = superior), workload (1-10 scale; 1 = superior), and
      global impressions (1-10 scale; 10 = superior) were recorded. Comparisons used
      analysis of variance (ANOVA) on ranks (Kruskal-Wallis), and p values lower than
      0.05 were considered significant. RESULTS: The operative outcomes were similar
      except for significantly higher blood loss with SSL (16.3 +/- 10.3) versus LAP
      (2.8 +/- 1.5; p < 0.05) but not with MAGS/PSS (4.8 +/- 3.8). Several inadvertent
      tissue-damaging events occurred with SSL but not with MAGS/PSS or LAP. The
      incision was significantly shorter with MAGS/PSS (29.3 +/- 2.8 mm) and SSL (29.3
      +/- 2.5 mm) than with LAP (48.0 +/- 3.6 mm; p < 0.05). Compared with SSL (3.6 +/-
      0.5), the procedure-specific ratings significantly favored MAGS/PSS (2.8 +/- 0.4)
      and LAP (1.7 +/- 0.2; p < 0.05). Ergonomics and technical challenges both were
      rated significantly inferior with SSL (4.3 +/- 1.0 and 3.8 +/- 0.5, respectively)
      versus LAP (1.5 +/- 0.6 and 2.0 +/- 0.8, respectively; p < 0.05) but not with
      MAGS/PSS (2.5 +/- 1.0 and 3.0 +/- 0.8, respectively). Both MAGS/PSS (4.5 +/- 0.5)
      and SSL (4.8 +/- 1.0) were associated with a significantly greater workload than
      LAP (2.5 +/- 0.6; p < 0.05). Global impression ratings were significantly higher
      for LAP (8.7 +/- 1.3) versus SSL (5.8 +/- 2.0; p < 0.05) but not for MAGS/PSS
      (7.1 +/- 1.8). Cosmesis was significantly better with MAGS/PSS (9.5 +/- 0.6)
      versus LAP (6.5 +/- 2.4; p < 0.05) but not with SSL (8.8 +/- 1.3). CONCLUSION:
      The MAGS/PSS technique allows better triangulation and fewer technical
      difficulties than SSL and better cosmesis than LAP. Further development of these
      devices is warranted.

PMID- 22648117
TI  - Adipogenic differentiation of adipose tissue-derived human mesenchymal stem
      cells: effect of gastric bypass surgery.
AB  - BACKGROUND: Adipose tissue dysfunction is an important feature of obesity
      characterized by enlarged adipocytes and marked changes in secretion of
      cytokines. These changes result in insulin resistance, chronic vascular
      inflammation, oxidative stress, and activation of the renin-angiotensin system
      (RAS), eventually leading to type 2 diabetes, obesity-related hypertension, and
      cardiovascular disease (CVD). Several trials have shown that bariatric surgery
      significantly reduces these comorbidities. However, there is a gap in knowledge
      regarding the mechanisms whereby bariatric surgery reduces the burden of CVD in
      obese individuals. METHOD: Mesenchymal stem cells (MSCs) were isolated from
      adipose tissue collected from three groups: (1) nonobese control subjects, (2)
      obese subjects undergoing gastric bypass surgery (GBS), and (3) subjects 1 year
      or more after GBS. In the study, MSCs were induced to adipogenic differentiation,
      and RAS-related gene expressions were determined by quantitative polymerase chain
      reaction. The effect of angiotensin II (Ang II) on adipogenic differentiation of
      MSCs also was investigated. RESULTS: Angiotensinogen mRNA levels in MSCs and
      differentiated adipocytes were significantly higher in the obese group than in
      the nonobese control subjects. Renin mRNA levels were significantly higher in the
      obese group MSCs than in the nonobese and post-GBS groups. Angiotensin-converting
      enzyme mRNA levels were significantly lower in the MSCs derived from the post-GBS
      group than in the obese and nonobese control subjects. Serum Ang II levels were
      significantly lower in the post-GBS group (52.1 +/- 4.2 pg/ml) than in the
      nonobese (85.4 +/- 12.4 pg/ml) and obese (84.7 +/- 10.0 pg/ml) groups. Ang II
      treatment inhibited adipogenesis of MSCs in a dose-dependent manner. The
      inhibitory effect of Ang II was mainly abolished by PD123319, a receptor 2
      blocker. CONCLUSIONS: The adipogenesis of MSCs is inhibited by Ang II treatment.
      Obese individuals are characterized by an upregulation of the RAS-related gene
      expressions in adipose tissue. This upregulation resolves in post-GBS subjects.

PMID- 22648119
TI  - Real-time three-dimensional soft tissue reconstruction for laparoscopic surgery.
AB  - BACKGROUND: Accurate real-time 3D models of the operating field have the
      potential to enable augmented reality for endoscopic surgery. A new system is
      proposed to create real-time 3D models of the operating field that uses a custom
      miniaturized stereoscopic video camera attached to a laparoscope and an image
      based reconstruction algorithm implemented on a graphics processing unit (GPU).
      METHODS: The proposed system was evaluated in a porcine model that approximates
      the viewing conditions of in vivo surgery. To assess the quality of the models, a
      synthetic view of the operating field was produced by overlaying a color image on
      the reconstructed 3D model, and an image rendered from the 3D model was compared
      with a 2D image captured from the same view. RESULTS: Experiments conducted with
      an object of known geometry demonstrate that the system produces 3D models
      accurate to within 1.5 mm. CONCLUSIONS: The ability to produce accurate real-time
      3D models of the operating field is a significant advancement toward augmented
      reality in minimally invasive surgery. An imaging system with this capability
      will potentially transform surgery by helping novice and expert surgeons alike to
      delineate variance in internal anatomy accurately.

PMID- 22648120
TI  - Short-term surgical outcomes and operative risks of laparoscopic total
      gastrectomy (LTG) for gastric carcinoma: experience at a large-volume center.
AB  - BACKGROUND: Despite the popularity of laparoscopic distal gastrectomy (LDG),
      laparoscopic total gastrectomy (LTG) remains a challenging procedure because of
      its technical difficulties and possible complications. In this study, the authors
      evaluated the short-term surgical outcomes and operative risks of LTG. METHODS:
      The records of 118 patients who underwent LTG for middle or upper gastric cancer
      were retrieved from a prospectively constructed database of 1,064 patients who
      underwent laparoscopic gastrectomy between 2007 and 2011. Surgical outcomes of
      LTG, such as operative results, postoperative courses, morbidities, and
      mortality, were investigated and compared with those of LDG patients. RESULTS: Of
      the 118 LTG patients, one underwent open conversion and three experienced an
      intraoperative complication. Mean operating time was 292 +/- 88 min, and the mean
      total number of harvested lymph nodes was 41 +/- 16. As compared with the LDG
      group, the LTG group had a significantly longer operation time (292 vs. 220 min,
      p < 0.001), and significantly more intraoperative blood loss (256 vs. 191 ml, p =
      0.002). The overall morbidity rate after LTG was 22.9%, which was significantly
      higher than after LDG (12.7%, p = 0.002). There were two postoperative
      mortalities in the LTG group. The most common complications after LTG were
      anastomosis leakage (n = 9) and luminal bleeding (n = 9), which were followed by
      anastomosis stricture (n = 4) and abdominal infection (n = 3). Univariate and
      multivariate analysis revealed that old age [>=60 years, odds ratio (OR) = 2.55,
      95% confidence interval (CI) = 0.95-6.84], intraoperative blood loss >200 ml (OR
      = 3.33, 95% CI = 1.14-9.70), and D2 lymphadenectomy (OR = 3.87, 95% CI = 1.30
      11.55) were independent risk factors for postoperative complications after LTG.
      CONCLUSIONS: LTG is a feasible and acceptable procedure for treatment of middle
      or upper early gastric cancer. Further refinement of anastomosis techniques and
      considerable experience of laparoscopic gastrectomy are required for proper
      application of LTG in gastric carcinoma.

PMID- 22648121
TI  - Data-based self-study guidelines for the fundamentals of laparoscopic surgery
      examination.
AB  - BACKGROUND: In preparing for the fundamentals of laparoscopic surgery (FLS) exam,
      residents usually adopt a self-learning strategy where practice time can be
      managed with more flexibility. However, with this self-learning strategy, there
      is a lack of direct supervision from experts and residents risk understudying for
      this high-stakes exam. Our objective is to determine study goals for effective
      self-guided practice for the FLS manual skills tasks that will result in passing
      the examination. METHODS: FLS manual skills data for all PGY-5 residents during
      2009-2010 was supplied by the FLS administrative office. Descriptive statistics
      were performed, and data were regrouped by the pass/fail results of the exam. The
      minimum practice time requirement for passing each manual skills task is reported
      in order to guide practice. RESULTS: 1,047 proctored FLS exams were completed by
      2009-2010 residents. Mean task time achieved by all residents was 84 +/- 31 s for
      peg transfer, 139 +/- 54 s for pattern cut, 78 +/- 29 s for endoloop, 158 +/- 66
      s for extracorporeal suturing, and 168 +/- 77 s for intracorporeal suturing. In
      the pass group (n = 988), mean time to complete each task was 80 s for peg
      transfer, 134 s for pattern cut, 75 s for endoloop, 148 s for extracorporeal
      suturing, and 160 s for intracorporeal suturing. Calculations suggest a self
      study goal for each task of 53 s for peg transfer, 50 s for pattern cut, 87 s for
      endoloop, 99 s for extracorporeal suturing, and 96 s for intracorporeal suturing.
      If a resident can reliably achieve these results during self-study, they have an
      84% chance of passing the exam. CONCLUSIONS: Residents preparing to take the FLS
      exam can refer to data presented in this study to set practice goals. Referring
      to these data-based practice goals will help residents to improve their chances
      of passing this high-stakes exam.

PMID- 22648122
TI  - Laparoscopic modified Sugarbaker technique results in superior recurrence rate.
AB  - BACKGROUND: Parastomal hernia (PH) is a frequent complication of stoma formation,
      occurring in 35-50% of patients. Recurrence after repair is common, ranging from
      24 to 54% of cases. We hypothesized that repair using a laparoscopic modified
      Sugarbaker technique (SB) would result in a superior recurrence rate when
      compared with other repairs. METHODS: An Institutional Review Board-approved
      retrospective review of patients who underwent PH repair between 2004 and 2011
      was performed. We collected demographics, factors related to ostomy formation,
      risk factors for hernia, intraoperative and postoperative information, as well as
      the absence or presence of PH on their last physical examination or imaging
      study. RESULTS: Forty-nine PH repairs were performed: 33 (67%) para-ileostomy and
      16 (33%) para-colostomy. Repairs included 14 laparoscopic modified SB, 19
      laparoscopic keyhole, 11 ostomy re-sitings, and 5 open primary repairs. There was
      no statistically significant difference between groups when comparing age, BMI,
      smoking status, steroid use, ostomy type, location, primary diagnoses, or
      complication rate. Recurrence rates were 0% for SB, 58% for keyhole, 64% for re
      siting, and 20% for open repair. When SB was compared with all groups, the
      incidence of recurrence was significantly lower (p < 0.001) but follow-up was as
      well (7.2 vs 32.7 months). When analysis was restricted to the 28 repairs
      performed between 2009 and 2011, there was no significant difference between the
      groups in terms of demographics or follow-up period (7.2 months for SB group
      versus 11.8 months for all others), but again there was a significant difference
      in recurrence (0 of 14 for the SB group vs 8 of 14, p < 0.01). In addition, there
      were no differences in postoperative complication rates among all techniques.
      CONCLUSION: The modified SB technique may offer patients a significant decrease
      in the risk of recurrence compared with other PH repair techniques with no
      significant increase in postoperative complications.

PMID- 22648123
TI  - Prospective randomized clinical trial comparing laparoscopic cholecystectomy and
      hybrid natural orifice transluminal endoscopic surgery (NOTES) (NCT00835250).
AB  - BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery
      (NOTES) is a technique still in experimental development whose safety and
      effectiveness call for assessment through clinical trials. In this paper we
      present a three-arm, noninferiority, prospective randomized clinical trial of 1
      year duration comparing the vaginal and transumbilical approaches for
      transluminal endoscopic surgery with the conventional laparoscopic approach for
      elective cholecystectomy. PATIENTS AND METHODS: Sixty female patients between the
      ages of 18 and 65 years who were eligible for elective cholecystectomy were
      randomized in a ratio of 1:1:1 to receive hybrid transvaginal NOTES (TV group),
      hybrid transumbilical NOTES (TU group) or conventional laparoscopy (CL group).
      The main study variable was parietal complications (wound infection, bleeding,
      and eventration). The analysis was by intention to treat, and losses were not
      replaced. RESULTS: Cholecystectomy was successfully performed on 94% of the
      patients. One patient in the TU group was reconverted to CL owing to difficulty
      in maneuvering the endoscope. After a minimum follow-up period of 1 year, no
      differences were noted in the rate of parietal complications. Postoperative pain,
      length of hospital stay, and time off from work were similar in the three groups.
      No patient developed dyspareunia. Surgical time was longer among cases in which a
      flexible endoscope was used (CL, 47.04 min; TV, 64.85 min; TU, 59.80 min).
      CONCLUSIONS: NOTES approaches using the flexible endoscope are not inferior in
      safety or effectiveness to conventional laparoscopy. The transumbilical approach
      with flexible endoscope is as effective and safe as the transvaginal approach and
      is a promising, single-incision approach.

PMID- 22648124
TI  - Does fellow participation in laparoscopic Roux-en-Y gastric bypass affect
      perioperative outcomes?
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) requires specialized
      training commonly acquired during a fellowship. We hypothesized that fellows
      affect patient outcomes and this effect varies during training. METHODS: We
      included all LRYGB from the 2005 to 2009 American College of Surgeons-National
      Surgical Quality Improvement Program database. Cases without trainees (attending)
      were compared to those with trainees of >=6 years (fellow). Outcomes were
      pulmonary, infectious, and wound complications and deep venous thrombosis (DVT).
      Multivariable regression controlled for age, BMI, and comorbidities. RESULTS: Of
      the 18,333 LRYGB performed, 4,349 (24%) were fellow cases. Fellow patients had a
      higher BMI (46.1 vs. 45.7, p < 0.001) and fewer comorbidities. Mortality was 0.2
      and 0.1% and overall morbidity was 4.8 and 6.0% for attending and fellow groups,
      respectively. On adjusted analysis, mortality was similar, but fellow cases had
      30% more morbidity (p = 0.001). Specifically, fellows increased the odds of
      superficial surgical site infections (SSSIs) [odds ratio (OR) = 1.4, p = 0.01],
      urinary infections (UTIs) (OR = 1.7, p = 0.002), and sepsis (OR = 1.5, p = 0.05).
      During the first 6 months, fellows increased the odds of DVT (OR = 4.7, p =
      0.01), SSIs (OR = 1.5, p = 0.001), UTIs (OR = 1.8, p = 0.004), and sepsis (OR =
      1.9, p = 0.008). By the second half of training, fellow cases demonstrated
      outcomes equivalent to attending cases. CONCLUSIONS: Involving fellows in LRYGB
      may increase DVT, SSIs, UTIs, and sepsis, especially early in training. By
      completion of their training, cases involving fellows exhibited outcomes similar
      to cases without trainees. This supports both the need for fellowship training in
      bariatric surgery and the success of training to optimize patient outcomes.

PMID- 22648125
TI  - Is laparoscopic surgery for recurrent Crohn's disease beneficial in patients with
      previous primary resection through midline laparotomy? A case-matched study.
AB  - BACKGROUND: Patients undergoing abdominal surgery for Crohn's disease are
      predisposed to recurrence requiring reoperation. The effectiveness of
      laparoscopic versus open resection in patients with previous intestinal resection
      for Crohn's through midline laparotomy is controversial. METHODS: Patients with
      previous open resection for intestinal Crohn's disease undergoing elective
      laparoscopic surgery for recurrent bowel disease from 1997 to 2011 were case
      matched with open counterparts based on age (+/-5 years), gender, body mass index
      (+/-2 kg/m(2)), American Society of Anesthesiologists (ASA) score, surgical
      procedure, and year of surgery (+/-3 years). Groups were compared using Chi
      square or Fisher exact tests for categorical and the Wilcoxon rank-sum test for
      quantitative data. RESULTS: 26 patients undergoing laparoscopic ileocolectomy (n
      = 14), proctocolectomy (n = 5), small bowel resection (n = 4), abdominoperineal
      resection (n = 1), extended right colectomy (n = 1), and strictureplasty (n = 1)
      were well matched to 26 patients undergoing open surgery. The number of previous
      operations, disease phenotypes, steroid use, and comorbidities were comparable in
      the two groups. There were no deaths, and three patients (12%) required
      conversion because of adhesions. Laparoscopic and open groups had statistically
      similar operating times (169 versus 158 min, p = 0.94), estimated blood loss (222
      versus 427 ml, p = 0.32), overall morbidity (39 versus 69%, p = 0.051),
      reoperation rates (8 versus 0%, p = 0.5), postoperative return of bowel function
      (3.5 +/- 1.4 versus 3.9 +/- 1.7 days, p = 0.3), mean length of hospital stay (6.4
      +/- 6.2 versus 6.9 +/- 3.5 days, p = 0.12), and readmission rates (8 versus 12%,
      p = 0.64). Wound infection rate was decreased after laparoscopic surgery (0
      versus 27%, p = 0.01). CONCLUSIONS: Surgery for recurrent Crohn's disease in
      patients with previous primary resection through laparotomy can be frequently and
      safely completed laparoscopically. Wound infection rates are reduced, but the
      recovery advantages of a minimally invasive approach are not maintained when
      compared with open surgery. The decision to operate laparoscopically should
      therefore be carefully calibrated.

PMID- 22648126
TI  - Effects of intraoperative breaks on mental and somatic operator fatigue: a
      randomized clinical trial (Surg Endosc 2011;25:12; 1245-1250).

PMID- 22648127
TI  - An allosteric enhancer of M4 muscarinic acetylcholine receptor function inhibits
      behavioral and neurochemical effects of cocaine.
AB  - RATIONALE: The mesostriatal dopamine system plays a key role in mediating the
      reinforcing effects of psychostimulant drugs like cocaine. The muscarinic M4
      acetylcholine receptor subtype is centrally involved in the regulation of
      dopamine release in striatal areas. Consequently, striatal M4 receptors could be
      a novel target for modulating psychostimulant effects of cocaine. OBJECTIVES: For
      the first time, we here addressed this issue by investigating the effects of a
      novel selective positive allosteric modulator of M4 receptors, VU0152100, on
      cocaine-induced behavioral and neurochemical effects in mice. METHODS: To
      investigate the effect of VU0152100 on the acute reinforcing effects of cocaine,
      we use an acute cocaine self-administration model. We used in vivo microdialysis
      to investigate whether the effects of VU0152100 in the behavioral studies were
      mediated via effects on dopaminergic neurotransmission. In addition, the effect
      of VU0152100 on cocaine-induced hyperactivity and rotarod performance was
      evaluated. RESULTS: We found that VU0152100 caused a prominent reduction in
      cocaine self-administration, cocaine-induced hyperlocomotion, and cocaine-induced
      striatal dopamine increase, without affecting motor performance. Consistent with
      these effects of VU0152100 being mediated via M4 receptors, its inhibitory
      effects on cocaine-induced increases in striatal dopamine were abolished in M4
      receptor knockout mice. Furthermore, selective deletion of the M4 receptor gene
      in dopamine D1 receptor-expressing neurons resulted in a partial reduction of the
      VU0152100 effect, indicating that VU0152100 partly regulates dopaminergic
      neurotransmission via M4 receptors co-localized with D1 receptors. CONCLUSIONS:
      These results show that positive allosteric modulators of the M4 receptor deserve
      attention as agents in the future treatment of cocaine abuse.

PMID- 22648128
TI  - Should hypertensive patients take vitamin D?
AB  - The prevalence of both hypertension and vitamin D deficiency is high. The
      discovery of the vitamin D receptor and its possible effects on components of the
      cardiovascular system influencing blood pressure, such as the renin angiotensin
      system, the heart, the kidney and the blood vessels, has generated the hope that
      vitamin D therapy could be a new target for the treatment for hypertensive
      patients. Cross-sectional studies have clearly shown an association between low
      levels of vitamin D and hypertension. This association is not as clear in
      longitudinal studies. Finally, evidence from randomized controlled trials
      specifically designed to test the hypothesis of a blood pressure lowering effect
      of vitamin D is weak. Therefore, there is actually not enough evidence to
      recommend giving vitamin D to reduce blood pressure in hypertensive patients.

PMID- 22648129
TI  - Unexpected and novel putative viruses in the sediments of a deep-dark permanently
      anoxic freshwater habitat.
AB  - Morphological diversity, abundance and community structure of viruses were
      examined in the deep and anoxic sediments of the volcanic Lake Pavin (France).
      The sediment core, encompassing 130 years of sedimentation, was subsampled every
      centimeter. High viral abundances were recorded and correlated to prokaryotic
      densities. Abundances of viruses and prokaryotes decreased with the depth,
      contrasting the pattern of virus-to-prokaryote ratio. According to fingerprint
      analyses, the community structure of viruses, bacteria and archaea gradually
      changed, and communities of the surface (0-10 cm) could be discriminated from
      those of the intermediate (11-27 cm) and deep (28-40 cm) sediment layers. Viral
      morphotypes similar to virions of ubiquitous dsDNA viruses of bacteria were
      observed. Exceptional morphotypes, previously never reported in freshwater
      systems, were also detected. Some of these resembled dsDNA viruses of
      hyperthermophilic and hyperhalophilic archaea. Moreover, unusual types of
      spherical and cubic virus-like particles (VLPs) were observed. Infected
      prokaryotic cells were detected in the whole sediment core, and their vertical
      distribution correlated with both viral and prokaryotic abundances. Pleomorphic
      ellipsoid VLPs were visible in filamentous cells tentatively identified as
      representatives of the archaeal genus Methanosaeta, a major group of methane
      producers on earth.

PMID- 22648130
TI  - Host factors and typhoid fever-associated intestinal perforation in children in
      Nigeria.

PMID- 22648131
TI  - Giant cell tumor of the sphenoid bone occurring during pregnancy: successful
      tumor extirpation via endoscopic transnasal transsphenoidal surgery.

PMID- 22648133
TI  - The effect of loss of visual input on muscle power in resistance trained and
      untrained young men and women.
AB  - Visual impairment has been shown to reduce muscle power when compared with that
      in sighted individuals. The purpose of this study was to assess whether the loss
      of visual input affects lower limb muscle power production in sighted men and
      women who are resistance trained and untrained. Twenty-seven college-aged
      participants (19-23 years) performed a seated double-leg press with and without
      visual input (resulting from being blindfold) in 2 separate counterbalanced
      trials. Lower limb concentric power was calculated by measuring the distance and
      time a leg press footplate was displaced while lifting 60% of 1-repetition
      maximum as quickly as possible. Loss of visual input reduced power output by 22.8
      W (-6.4%) in all participants (p < 0.01). When resistance training status was
      taken into account, resistance trained participants (n = 12, trained >2* per
      week) did not lose power output (4.4 W, -1.1%, p = 0.90), whereas untrained men
      and women (n = 15) had significantly less power when visual input was removed via
      blindfold (37.6 W, -11.7%, p < 0.01). Untrained women experienced the greatest
      decrease in power when blindfolded (39 W, -15.9%, p < 0.01). Muscle power
      decreases in the absence of vision, but a regular strength training program
      attenuates this occurrence in young men and women. In practical application,
      strength training interventions may be successful in protecting individuals from
      losses in muscle power when visual input is removed.

PMID- 22648134
TI  - Effect of altitude on football performance: analysis of the 2010 FIFA World Cup
      Data.
AB  - Laboratory studies show that altitude ascent impairs endurance performance.
      Limited data exist on football, and information from official matches is very
      scarce even for other team sports. The aim of this study was to examine the
      effect of altitude on football performance during the 2010 World Cup in South
      Africa. It was hypothesized that (a) total distance covered, an index of
      endurance, would be reduced above the altitude of 580 m, and (b) technical skills
      would be affected because altitude alters ball flight characteristics. Physical
      performance, goals scored, and goalkeepers' errors that resulted in goals
      conceded were recorded from the official game statistics of Federation
      Internationale de Football Association during the South Africa 2010 World Cup.
      Matches were played at sea level (altitude: 0 m), 660, 1200-1400, and 1401-1753
      m. After testing for data normality, mean differences were checked with a one-way
      analysis of variance. Results show a 3.1% lower total distance that was covered
      by the teams during the matches played at 1200-1400 and 1401-1753 m (p < 0.05)
      compared with sea level. Indices of technical skills, including number of goals
      scored per game and errors made by the goalkeepers that resulted in goals
      conceded, did not differ with altitude. It is concluded that playing football
      above 1200 m had negative effects on endurance but not on technical skills during
      World Cup 2010 matches. It seems that teams should follow several days of
      acclimatization before playing at altitude as low as 1200 m, to ameliorate the
      negative effects of altitude on physical performance.

PMID- 22648136
TI  - Influence of different training regimes on physical and physiological demands
      during small-sided soccer games: continuous vs. intermittent format.
AB  - The aim of this study was to examine the physical and heart rate (HR) response of
      soccer players during 16 minutes of training using the same 5 vs. 5 small-sided
      game (SSG) in 3 different training regimes: a continuous format of 16 minutes and
      2 intermittent formats (4 periods of 4 minutes; and 2 periods of 8 minutes) with
      the same work/rest ratio of passive recovery between the different periods (4:1).
      Ten male players (age 21.3 +/- 3.4 years) belonging to a team of the third
      Spanish division participated in this study. Analyses were carried using a
      training regimen vs. drill time design (i.e., training * duration), that is,
      differentiating 2 training regimen (intermittent vs. continuous SSG formats) and
      the 4-minute periods (0-4, 4-8, 8-12, and 12-16 minutes) to determine the extent
      to which fatigue affected the variables studied in each regimen. During each SSG,
      HR and total distance covered in different speed categories and accumulated
      accelerations (i.e., training load) were measured. Results showed significant
      differences for (a) in intermittent format of 2 * 8 minutes, the distance covered
      at a speed of 7-12.9 km.h(-1) was greater in the 0- to 4-minute period than in
      the 12- to 16-minute period, and (b) the distance covered at a speed of 7-12.9
      km.h(-1) during the 8- to 12-minute period was greater in intermittent format of
      2 * 8 minutes than in continuous format (16 minutes). This study showed that
      drill regimen may affect physical responses during training SSG. The resulting
      evidence suggests that the continuous SSG format induces greater physical loads
      on players as compared with intermittent SSG format and that should help coaches
      to establish a better distribution of playing according to the objectives of the
      training.

PMID- 22648137
TI  - Commitment to strength and conditioning: a sport commitment model perspective.
AB  - The purpose of this study was to empirically apply the sport commitment
      constructs within the realm of strength and conditioning. Based on prior research
      in the sport domain, it was predicted that higher enjoyment, investments,
      benefits, and social support and lower perceived costs and attractive
      alternatives would predict higher commitment to strength and conditioning. With a
      sample of 191 intercollegiate male and female athletes, a pilot study was
      conducted to examine the predictors of commitment to strength and conditioning.
      Multiple regression analysis revealed that the strongest predictors of strength
      and conditioning commitment were perceived investments, benefits, enjoyment,
      costs, and attractive alternatives. Interestingly, differences emerged between
      men and women regarding the most salient predictors of commitment to strength and
      conditioning. Gender differences also emerged with male athletes reporting higher
      perceptions of enjoyment, benefits, and perceived obligation to their best friend
      to continue strength and conditioning. These findings are important both
      theoretically and practically. The Sport Commitment Model may provide an avenue
      to gain a further insight into strength and conditioning motivation, and
      providing practical strategies for increasing athletes' commitment: increasing
      enjoyment and perceived benefits, and decreasing perceived downsides and
      attractive alternatives.

PMID- 22648138
TI  - Influence of exercise order on the number of repetitions, oxygen uptake, and rate
      of perceived exertion during strength training in younger and older women.
AB  - The study investigated the effect of resistance exercise order on the number of
      repetitions, oxygen uptake (VO(2max)) and rate perceived exertion (RPE) in
      younger (YG: N = 10; 22 +/- 2 years; VO(2peak) 42.2 +/- 2.9 ml.kg(-1).min(-1))
      and older (EG: N = 8; 69 +/- 7 years; VO(2peak)22.7 +/- 2.5 ml.kg(-1).min(-1))
      women. The subjects performed 3 sets of each exercise until fatigue using 10
      repetition maximum in 2 sequences of opposite order: (a) sequence A (SEQA): bench
      press (BP), machine shoulder press (SP), pulley triceps extension (TE); (b)
      sequence B (SEQB): TE-SP-BP. The VO(2) was assessed during the exercises, rest
      intervals, and 20 minutes after sequences (postexercise oxygen consumption
      [EPOC]). The number of repetitions decreased in both groups (p < 0.05) throughout
      sets. No difference (p > 0.22) was found between sequences for total VO(2)
      (exercise sequences + EPOC) in YG (SEQA = 25.41 +/- 6.51 L vs. SEQB = 24.81 +/-
      4.08 L) and EG (SEQA = 26.45 +/- 5.24 L vs. SEQB = 26.91 +/- 4.62 L). In both
      groups, the VO(2) within the sequences was higher during BP when it was placed at
      the end of SEQB, the same occurring with TE in SEQA (p < 0.05). The VO(2) within
      sequences and RPE were higher in SEQB compared with SEQA (p < 0.05) in EG but not
      in YG. In conclusion, the exercise order did not affect total VO(2). The VO(2)
      within a given sequence was always lower when an exercise was performed first as
      compared with last regardless of the exercise order. Accumulated fatigue
      reflected by the VO(2) within sequences and RPE was influenced by the exercise
      order only in EG, suggesting that to prevent early fatigue, resistance training
      sessions in this group should preferably progress from large toward small-muscle
      group exercises.

PMID- 22648139
TI  - Lactate response to different volume patterns of power clean.
AB  - The ability to metabolize or tolerate lactate and produce power simultaneously
      can be an important determinant of performance. Current training practices for
      improving lactate use include high-intensity aerobic activities or a combination
      of aerobic and resistance training. Excessive aerobic training may have undesired
      physiological adaptations (e.g., muscle loss, change in fiber types). The role of
      explosive power training in lactate production and use needs further
      clarification. We hypothesized that high-volume explosive power movements such as
      Olympic lifts can increase lactate production and overload lactate clearance.
      Hence, the purpose of this study was to assess lactate accumulation after the
      completion of 3 different volume patterns of power cleans. Ten male recreational
      athletes (age 24.22 +/- 1.39 years) volunteered. Volume patterns consisted of 3
      sets * 3 repetition maximum (3RM) (low volume [LV]), 3 sets * 6 reps at 80-85% of
      3RM (midvolume [MV]), and 3 sets * 9 reps at 70-75% of 3RM (high volume [HV]).
      Rest period was identical at 2 minutes. Blood samples were collected immediately
      before and after each volume pattern. The HV resulted in the greatest lactate
      accumulation (7.43 +/- 2.94 mmol.L) vs. (5.27 +/- 2.48 and 4.03 +/- 1.78 mmol.L
      in MV and LV, respectively). Mean relative increase in lactate was the highest in
      HV (356.34%). The findings indicate that lactate production in power cleans is
      largely associated with volume, determined by number of repetitions, load, and
      rest interval. High-volume explosive training may impose greater metabolic
      demands than low-volume explosive training and may improve ability to produce
      power in the presence of lactate. The role of explosive power training in
      overloading the lactate clearance mechanism should be examined further,
      especially for athletes of intermittent sport.

PMID- 22648140
TI  - Concurrent validity of vertical jump performance assessment systems.
AB  - The aim of this study was to examine the concurrent validity of 2 portable
      systems for vertical jump (VJ) assessment under field conditions. The VJ flight
      times assessed using an optical mat (Optojump) and an accelerometer-based
      (Myotest) system were compared with that of a force platform. The flight times
      recorded during a countermovement jump (CMJ) were collected from 20 rugby players
      (n = 86 jumps) concurrently using the 3 tracking systems. Significant bias
      between the Force platform and either the Optojump (bias = 0.006 +/- 0.007; 95%
      confidence interval [CI] 0.004-0.007 seconds) and Myotest (bias = -0.031 +/-
      0.021; 95% CI 0.035 to -0.026s; p < 0.0001) occurred. A nearly perfect
      correlation was found between force platform and Optojump (r = 0.99; 95% CI 0.098
      0.99; p < 0.0001). Force platform and Myotest (r = 0.89; 95% CI 0.084-0.93; p <
      0.0001) flight times showed very large association. Difference between Optojump
      and Myotest systems was significant (-0.036 +/- 0.021 seconds; 95% CI -0.041 to 
      0.032; p < 0.0001), which results in Myotest mean flight time being approximately
      7.2% longer than the Optojump flight time. The association between Optojump and
      Myotest was nearly perfect (r = 0.91, 95% CI 0.86-0.94; p < 0.0001). This study
      showed that the Optojump and Myotest systems possess convergent validity and can
      be successfully used under field conditions to assess VJ while performing a CMJ.
      However, caution should be exercised when interpreting data obtained from
      different portable systems for field measurement.

PMID- 22648141
TI  - Individual training-load and aerobic-fitness variables in premiership soccer
      players during the precompetitive season.
AB  - The aim of this study was to examine the association between individual measures
      of internal training load (training impulse [TRIMPi]) and aerobic-fitness and
      performance variables in premiership male soccer players. Eighteen Premiership
      soccer players (age 28.4 +/- 3.2 years, height 182 +/- 5.3 cm, body mass 79.9 +/-
      5.5 kg) performed treadmill tests for VO(2max) and ventilatory threshold (VT) and
      speed at blood-lactate concentration of 4 mmol.L(-1) (S4) on separate days pre
      and post 8 weeks of training (preseason). The Yo-Yo Intermittent recovery test
      (Yo-Yo IR1) performance was assessed pre and post preseason training as well. The
      TRIMPi was calculated using individual lactate and heart-rate profiles and
      assessed in each training session (n = 900). The results showed that TRIMPi was
      large to very-large associated with percentage changes in VO(2max) (r = 0.77, p =
      0.002), VT (r = 0.78, p = 0.002), S4 (r = 0.64, p = 0.004), and Yo-Yo IR1
      performance (r = 0.69, p = 0.009). Regression analyses showed that a weekly
      TRIMPi >500 AU was necessary to warrant improvements in aerobic fitness and
      performance in premiership male soccer players during the precompetitive season.
      It is concluded that TRIMPi is a valid and viable tool to guide training
      prescription in male premiership soccer players during the preseason.

PMID- 22648142
TI  - The effect of cadence on cycling efficiency and local tissue oxygenation.
AB  - The purpose of this study was to compare 3 cycling cadences in
      efficiency/economy, local tissue oxygen saturation, heart rate, blood lactate,
      and global and local rating of perceived exertion (RPE). Subjects were 14 trained
      cyclists/triathletes (mean age 30.1 +/- 5.3 years; VO(2) peak 60.2 +/- 5.0 ml.kg(
      1).min(-1)) who performed three 8-minute cadence trials (60, 80, and 100 rpm) at
      75% of previously measured peak power. Oxygen consumption and respiratory
      exchange ratio were used to calculate efficiency and economy. Results indicated
      that both efficiency and economy were higher at the lower cadences. Tissue oxygen
      saturation was greater at 80 rpm than at 60 or 100 rpm at minute 4, but at minute
      8, tissue oxygen saturation at 80 rpm (57 +/- 9%) was higher than 100 rpm (54 +/-
      9%, p = 0.017) but not at 60 rpm (55 +/- 11%, p = 0.255). Heart rate and lactate
      significantly increased from minute 4 and minute 8 (p < 0.05) of submaximal
      cycling. Local RPE at 80 rpm was lower than at 60 or 100 rpm (p < 0.05). It was
      concluded that (a) Trained cyclists and triathletes are more efficient and
      economical when cycling at 60 rpm than 80 or 100 rpm. (b); Local tissue oxygen
      saturation levels are higher at 80 rpm than 60 and 100 rpm; (c). Heart rate and
      blood lactate levels are higher with cadences of 80 and 100 than 60 rpm; and (d).
      Local and global RPE is lower when cycling at 80 rpm than at 60 rpm and 100 rpm.
      A practical application of these findings is that a cadence of 60 rpm may be
      advantageous for performance in moderately trained athletes in contrast to higher
      cadences currently popular among elite cyclists.

PMID- 22648143
TI  - Performance changes in NBA basketball players vary in starters vs. nonstarters
      over a competitive season.
AB  - The purpose of this study was to compare starters (S) with nonstarters (NS), on
      their ability to maintain strength, power, and quickness during a competitive
      National Basketball Association (NBA) season. Twelve NBA players were assessed at
      the beginning and end of the competitive season. However, because of trades and
      injury, only 7 (S = 4, NS = 3) players (28.2 +/- 3.4 years; 200.9 +/- 9.4 cm;
      104.7 +/- 13.9 kg; 7.2 +/- 1.9% body fat) participated in both testing sessions
      and underwent analysis. Anthropometric performance (repetitive vertical jump
      power [VJP], squat power [SQT power], and reaction time) and subjective feelings
      of energy, focus, alertness, and fatigue were recorded during each testing
      session. Results were interpreted using magnitude-based statistics to make
      inferences on true differences between starters and nonstarters using the unequal
      variances t-statistic. Starters played an average of 27.8 +/- 6.9 minutes per
      game and nonstarters played an average of 11.3 +/- 7.0 minutes per game. During
      the course of the season, changes in VJP indicated that starters were likely to
      increase VJP (Delta = 77.3 +/- 78.1 W) compared to nonstarters (Delta= -160.0 +/-
      151.0 W). There also appeared to be a possible beneficial effect on maintaining
      reaction time in starters (Delta = 0.005 +/- 0.074 seconds) compared with
      nonstarters (Delta = 0.047 +/- 0.073 seconds). In addition, no clear differences
      in DeltaSQT power were seen between starters (Delta = 110.8 +/- 141.4 W) and
      nonstarters (Delta = 143.5 +/- 24.7 W). Changes in subjective feelings of energy
      indicated that starters were very likely to maintain their energy over the course
      of a season. It also appeared possible that starters were able to have a more
      positive response to subjective measures of fatigue and alertness than
      nonstarters, with only trivial differences between starters and nonstarters in
      regards to maintaining focus. Results of this study suggest that NBA players may
      enhance lower-body power, repetitive jump ability, and reaction during a
      competitive season, which appear to be enhanced with the stimulus of playing
      time.

PMID- 22648145
TI  - Validation of vibration testing for the assessment of the mechanical properties
      of human lumbar motion segments.
AB  - Experimental modal analysis is a non-destructive measurement technique, which
      applies low forces and small deformations to assess the integrity of a structure.
      It is therefore a promising method to study the mechanical properties of the
      spine in vivo. Previously, modal parameters successfully revealed artificially
      induced spinal injuries. The question remains however, whether experimental modal
      analysis can be applied successfully in human spinal segments with mechanical
      changes due to physiological processes. Since quasi-static mechanical testing is
      considered the "gold standard" for assessing intervertebral stiffness, the
      purpose of our study was to examine if the mechanical properties derived from
      vibration testing and quasi-static testing correlate. Six cadaver human spines
      (L1-L5) were loaded quasi-statically in bending and torsion, while an optical
      system measured the angular rotations of the individual motion segments.
      Subsequently, the polysegmental spines were divided into L2-L3 and L4-L5 segments
      and a shaker was used to vibrate the upper vertebra, while its response was
      obtained from accelerometers in anteroposterior and mediolateral directions. From
      the resulting frequency response function the eigenfrequencies (ratio between
      stiffness and mass) and vibration modes (pattern of motion) were determined. The
      vibration results showed clear eigenfrequencies for flexion-extension (mean
      121.83Hz, SD 40.05Hz), lateroflexion (mean 132.17, SD 34.80Hz) and axial rotation
      (mean 236.17Hz, SD 81.45Hz). Furthermore, the correlation between static and
      dynamic tests was significant (r=0.73, p=0.01). In conclusion, the findings from
      this study show that experimental modal analysis is a valid method to assess the
      mechanical properties of human lumbar motion segments.

PMID- 22648144
TI  - Mechanical properties of porcine femoral cortical bone measured by
      nanoindentation.
AB  - This study uses a nanoindentation technique to examine variations in the local
      mechanical properties of porcine femoral cortical bone under hydrated conditions.
      Bone specimens from three age groups (6, 12 and 42 months), representing
      developing bone, ranging from young to mature animals, were tested on the
      longitudinal and transverse cross-sectional surfaces. Elastic modulus and
      hardness of individual lamellae within bone's microstructure: laminar bone,
      interstitial bone, and osteons, were measured. Both the elastic modulus and
      hardness increased with age. However, the magnitudes of these increases were
      different for each microstructural component. The longitudinal moduli were higher
      than the transverse moduli. Dehydrated samples were also tested to allow a
      comparison with hydrated samples and these resulted in higher moduli and hardness
      than the hydrated samples. Again, the degree of variation was different for each
      microstructural component. These results indicate that the developmental changes
      in bone have different rates of mechanical change within each microstructural
      component.

PMID- 22648146
TI  - Fracture risk in the femoral hip region: A finite element analysis supported
      experimental approach.
AB  - The decrease of bone mineral density (BMD) is a multifactorial bone pathology,
      commonly referred to as osteoporosis. The subsequent decline of the bone's micro
      structural characteristics renders the human skeletal system, and especially the
      hip, susceptible to fragility fractures. This study represents a systematic
      attempt to correlate BMD spectrums to the mechanical strength characteristics of
      the femoral neck and determine a fracture risk indicator based on non-invasive
      imaging techniques. The BMD of 30 patients' femurs was measured in vivo by Dual
      energy X-ray absorptiometry (DXA). As these patients were subjected to total hip
      replacement, the mechanical strength properties of their femurs' were determined
      ex-vivo using uniaxial compression experiments. FEA simulations facilitated the
      correlation of the DXA measurements to the apparent fracture risk, indicating
      critical strain values during complex loading scenarios.

PMID- 22648147
TI  - Amplitude effects of medio-lateral mechanical and visual perturbations on gait.
AB  - Falls during walking are a major contributor to accidental deaths and injuries
      that can result in debilitating hospitalization costs, lost productivity, and
      diminished quality of life. To reduce these losses, we must develop a more
      profound understanding of the characteristic responses to perturbations similar
      to those encountered in daily life. This study addresses this issue by building
      on our earlier studies that examined mechanical and visual perturbations in the
      same environment by applying the same continuous pseudo-random perturbations at
      multiple (3 mechanical, 5 visual) amplitudes. Walking variability during
      mechanical perturbations increased significantly with amplitude for all subjects
      and differences as measured by variabilities of step width, COM position, and COM
      velocity. These parameters were the only ones sensitive to the presence of visual
      perturbations, but none of them changed significantly with perturbation
      amplitude. Additionally, visual perturbation effects were far less consistent
      across participants, with several who were essentially unaffected by visual
      perturbations at any level. The homogeneity of the mechanical perturbation
      effects demonstrates that human responses to mechanical perturbations are similar
      because they are driven by kinetics that require similar corrections that must be
      made in order to maintain balance. Conversely, responses to visual perturbations
      are driven by the perceived need to make corrections and this perception is not
      accurate enough to produce amplitude-related corrections, even for a single
      participant, nor is this perception consistent across individuals. This latter
      finding is likely to be relevant to future visual perturbation studies and the
      diagnosis and rehabilitation of gait and balance disorders.

PMID- 22648148
TI  - Long-term response to vaccination against pneumococcal antigens in kidney
      transplant recipients.
AB  - BACKGROUND: We have recently shown that kidney transplant recipients with
      clinically stable condition can produce almost normal antibody concentrations at
      month 1 after vaccination against Streptococcus pneumoniae. It was the aim of the
      present study to define the long-term efficacy of this vaccination in a similar
      cohort. METHODS: Using Pneumovax 23, we immunized 49 kidney transplant recipients
      (21 women and 28 men, aged 29-74 years). Antibodies against 14 pneumococcal
      serotypes were determined before vaccination and at months 1 and 15 after
      vaccination by Luminex assay. RESULTS: The total antibody concentration (median
      [range]) increased from 18.2 mg/L (2.9-55.5 mg/L) before vaccination to 53.6 mg/L
      (4.5-132.4 mg/L) at month 1 and 41.3 mg/L (4.9-105.0 mg/L) at month 15 (P<0.0001
      as compared with before vaccination). The antibody concentration at month 15 was
      77% of the response at month 1. The number of pneumococcal serotypes recognized
      was 8 (0-13) before vaccination, 13 (0-14) at month 1, and 11 (0-14) at month 15.
      At month 15, the total antibody concentration and the number of serotypes with
      protective antibodies already displayed a significant decrease (P<0.0001 each) as
      compared with month 1. It could be shown that the decrease in antibody
      concentrations (months 1-15) was minor in younger patients, in women, in patients
      receiving cyclosporine A versus tacrolimus, and in patients with better kidney
      function. CONCLUSIONS: Our results demonstrate that, at month 15 after
      vaccination versus before vaccination, kidney transplant recipients with
      clinically stable condition still display higher antibody concentrations against
      pneumococci. Therefore, they should be partly protected against pneumococcal
      infection until month 15.

PMID- 22648149
TI  - Outcomes of pancreas allografts procured simultaneously with an isolated
      intestine allograft:  single-center and national data.
AB  - BACKGROUND: Simultaneous procurement of pancreas and isolated intestine
      allografts from the same donor may compromise one graft or both given the shared
      vasculature between these two organs. This study reports the transplant outcomes
      for pancreas allografts procured simultaneously with an intestine graft. METHODS:
      Separate analyses are reported from (1) 10-year US national data obtained from
      the United Network for Organ Sharing database including all donors from 2000 to
      2010 in whom both the pancreas and isolated intestine were procured and
      transplanted into separate recipients and (2) local, single-center data for all
      donors of simultaneous pancreas and isolated intestine procurement. Scientific
      Registry of Transplant Recipients reference data are provided for comparison.
      RESULTS: Nationally, there were 159 simultaneous pancreas and intestine donors.
      The mean pancreas transplant graft and patient survival rates for this cohort
      were 75% and 93%, respectively. There were 34 isolated intestine allografts
      procured by our center during the study period. There were 14 cases (41%) in
      which the pancreas was transplanted. The reasons for nontransplantation of the
      pancreas in the other 20 donors included donor age (n=12), graft quality (n=4),
      and anatomic or surgical issues (n=4). For the 14 transplanted grafts, 1-year
      pancreas allograft survival rate was 100%. CONCLUSIONS: These results suggest
      that pancreas allografts procured simultaneously with an isolated intestine
      graft, although technically more challenging, do not have significantly inferior
      survival outcomes.

PMID- 22648150
TI  - Prodrugs of theophylline incorporating ethyleneoxy groups in the promoiety:
      synthesis, characterization, and transdermal delivery.
AB  - Two different types of derivatives of theophylline (Th-H) incorporating
      ethyleneoxy groups into the promoiety have been synthesized. One is a soft alkyl
      type where N-methyl-N-methoxyethyleneoxycarbonylaminomethyl chlorides have been
      used to alkylate Th-H in the 7 position. The other is in an acyl type where
      methoxyethyleneoxycarbonyl chlorides have been used to acylate Th-H in the 7
      position. All of the prodrugs were more soluble in the lipid isopropyl myristate
      (IPM) than Th-H, and three were more soluble in water (AQ) than Th-H. The most
      water-soluble prodrug gave the highest maximum delivery of total species
      containing Th-H through hairless mouse skin from IPM (maximum flux, J(MMIPM))
      more than seven times that of Th-H, while the other two gave more than three
      times that of Th-H. The acyl-type prodrugs delivered only Th-H, while the soft
      alkyl types delivered 60-70% Th-H plus intact prodrug. The Roberts-Sloan equation
      was able to predict the best performer for each type with an average of the
      absolute difference between the experimental log J (MMIPM) and calculated log J
      (MMIPM) (Deltalog J (MMIPM)) of 0.253 log units. The values for the present
      prodrugs and previously reported prodrugs that had not been previously included
      in the Roberts-Sloan data base (n = 23) were included in the previous n = 71 data
      base to give n = 94. New coefficients for the Roberts-Sloan equation have been
      obtained.

PMID- 22648151
TI  - Epicardial halo phenomenon: a guide for pericardiocentesis?
AB  - The epicardial halo delineates the heart shadow in fluoroscopy. To establish
      whether the sign is applicable to pericardiocentesis guidance, three
      investigators evaluated its intensity as absent = grade 0, indistinct = 0.5,
      clear = 1, intensive = 2 in posterior-anterior (PA) and lateral fluoroscopies
      recorded before pericardiocentesis or cardiac catheterization (Philips Integris
      II BH3000). Three populations were studied: (a) 32 patients with pericardial
      effusion (PE group), 53.1 % males, aged 53.9 +/- 13.9 years; (b) 14 patients with
      perimyocarditis (PM group), 64.3 % males, aged 51.6 +/- 14.4 years; and (c) 46
      coronary patients (CAD group), no PE, 95.6 % males, aged 67.3 +/- 11.8 years. The
      intensity of the halo phenomenon was highest in patients with PE, lowest in
      patients with CAD, and intermediate in patients with PM (median sum of grades in
      PA/lateral view: 4/5 vs. 2/2.5 vs. 3/3, respectively) (p < 0.01). The halo
      phenomenon correlated well with HR and echocardiographic PE size in both
      angiographic views. The correlation with body mass index (BMI) and age was
      significant only in the lateral view and with PE volume only in the PA view. The
      sensitivity of the halo sign for PE was 84.1 % in PA and 92.0 % in lateral views.
      In 10/32 PE patients, the evaluation of the sign was repeated after PE drainage,
      revealing lower grades both in PA and in lateral views (p < 0.01). In conclusion,
      the epicardial halo sign is highly sensitive for the detection of a PE; it
      correlates well in at least one angiographic projection with the PE volume, HR,
      age, BMI, and the PE size in echocardiography and could be therefore applied as a
      safety guide for pericardiocentesis.

PMID- 22648152
TI  - [Slight reduction of cardiovascular risk by modified dietary fat].

PMID- 22648153
TI  - A tropical bird can use the equatorial change in sunrise and sunset times to
      synchronize its circannual clock.
AB  - At higher latitudes, most organisms use the periodic changes in day length to
      time their annual life cycle. At the equator, changes in day length are minimal,
      and it is unknown which cues organisms use to synchronize their underlying
      circannual rhythms to environmental conditions. Here, we demonstrate that the
      African stonechat (Saxicola torquatus axillaris)-an equatorial songbird-can use
      subtle solar cues for the annual timing of postnuptial moult, a reliable marker
      of the circannual cycle. We compared four groups that were kept over more than 3
      years: (i) a control group maintained under constant equatorial day length, (ii)
      a 12-month solar time group maintained under equatorial day length, but including
      a simulation of the annual periodic change in sunrise and sunset times (solar
      time), (iii) a 14-month solar time group similar to the previous group but with
      an extended solar time cycle and (iv) a group maintained under a European
      temperate photoperiod. Within all 3 years, 12-month solar time birds were
      significantly more synchronized than controls and 14-month solar time birds.
      Furthermore, the moult of 12-month solar time birds occurred during the same time
      of the year as that of free-living Kenyan conspecifics. Thus, our data indicate
      that stonechats may use the subtle periodic pattern of sunrise and sunset at the
      equator to synchronize their circannual clock.

PMID- 22648154
TI  - Kin selection, quorum sensing and virulence in pathogenic bacteria.
AB  - Bacterial growth and virulence often depends upon the cooperative release of
      extracellular factors excreted in response to quorum sensing (QS). We carried out
      an in vivo selection experiment in mice to examine how QS evolves in response to
      variation in relatedness (strain diversity), and the consequences for virulence.
      We started our experiment with two bacterial strains: a wild-type that both
      produces and responds to QS signal molecules, and a lasR (signal-blind) mutant
      that does not release extracellular factors in response to signal. We found that:
      (i) QS leads to greater growth within hosts; (ii) high relatedness favours the QS
      wild-type; and (iii) low relatedness favours the lasR mutant. Relatedness matters
      in our experiment because, at relatively low relatedness, the lasR mutant is able
      to exploit the extracellular factors produced by the cells that respond to QS,
      and hence increase in frequency. Furthermore, our results suggest that because a
      higher relatedness favours cooperative QS, and hence leads to higher growth, this
      will also lead to a higher virulence, giving a relationship between relatedness
      and virulence that is in the opposite direction to that usually predicted by
      virulence theory.

PMID- 22648155
TI  - Oxidative stress and condition-dependent sexual signals: more than just seeing
      red.
AB  - The links between fitness, health, sexual signals and mate choice are complex and
      subject to ongoing study. In 1999, von Schantz et al. made the valuable
      suggestion that oxidative stress may be an important missing piece of this
      complex puzzle. Their suggestion has been enthusiastically tested, with over 300
      studies citing their paper, but most effort has concerned carotenoid-based (and
      to a lesser extent melanin-based) visual signals, predominantly in birds and
      fishes. Today, we know a great deal more about oxidative stress and related
      physiology, in both a pathological and regulatory sense, than we did in 1999. We
      revisit von Schantz et al.'s predictions and, more importantly, highlight novel
      mechanisms that could link oxidative stress with a range of energetically
      demanding signals, greatly increasing the scope from visual signalling systems
      that are usually discussed and nearly always tested. In particular, we argue that
      differences between individuals in their ability to regulate physiology related
      to oxidative stress may be an important factor influencing the production of
      sexual signals and the costs that are incurred from investment.

PMID- 22648156
TI  - Socially flexible female choice differs among populations of the Pacific field
      cricket: geographical variation in the interaction coefficient psi (Psi).
AB  - Indirect genetic effects (IGEs) occur when genes expressed in one individual
      affect the phenotype of a conspecific. Theoretical models indicate that the
      evolutionary consequences of IGEs critically depend on the genetic architecture
      of interacting traits, and on the strength and direction of phenotypic effects
      arising from social interactions, which can be quantified by the interaction
      coefficient Psi. In the context of sexually selected traits, strong positive Psi
      tends to exaggerate evolutionary change, whereas negative Psi impedes sexual
      trait elaboration. Despite its theoretical importance, whether and how Psi varies
      among geographically distinct populations is unknown. Such information is
      necessary to evaluate the potential for IGEs to contribute to divergence among
      isolated or semi-isolated populations. Here, we report substantial variation in
      Psi for a behavioural trait involved in sexual selection in the field cricket
      Teleogryllus oceanicus: female choosiness. Both the strength and direction of Psi
      varied among geographically isolated populations. Psi also changed over time. In
      a contemporary population of crickets from Kauai, experience of male song
      increased female choosiness. In contrast, experience of male song decreased
      choosiness in an ancestral population from the same location. This rapid change
      corroborates studies examining the evolvability of Psi and demonstrates how
      interpopulation variation in the interaction coefficient might influence sexual
      selection and accelerate divergence of traits influenced by IGEs that contribute
      to reproductive isolation in nascent species or subspecies.

PMID- 22648157
TI  - Host-parasite coevolution beyond the nestling stage? Mimicry of host fledglings
      by the specialist screaming cowbird.
AB  - Egg mimicry by obligate avian brood parasites and host rejection of non-mimetic
      eggs are well-known textbook examples of host-parasite coevolution. By contrast,
      reciprocal adaptations and counteradaptations beyond the egg stage in brood
      parasites and their hosts have received less attention. The screaming cowbird
      (Molothrus rufoaxillaris) is a specialist obligate brood parasite whose
      fledglings look identical to those of its primary host, the baywing (Agelaioides
      badius). Such a resemblance has been proposed as an adaptation in response to
      host discrimination against odd-looking young, but evidence supporting this idea
      is scarce. Here, we examined this hypothesis by comparing the survival rates of
      young screaming cowbirds and non-mimetic shiny cowbirds (Molothrus bonariensis)
      cross-fostered to baywing nests and quantifying the similarity in plumage colour
      and begging calls between host and cowbird fledglings. Shiny cowbirds suffered
      higher post-fledging mortality rates (83%) than screaming cowbirds (0%) owing to
      host rejection. Visual modelling revealed that screaming cowbirds, but not shiny
      cowbirds, were indistinguishable from host young in plumage colour. Similarly,
      screaming cowbirds matched baywings' begging calls more closely than shiny
      cowbirds. Our results strongly support the occurrence of host fledgling mimicry
      in screaming cowbirds and suggest a role of visual and vocal cues in fledgling
      discrimination by baywings.

PMID- 22648158
TI  - Fairness modulates non-conscious facial mimicry in women.
AB  - In societies with high cooperation demands, implicit consensus on social norms
      enables successful human coexistence. Mimicking other people's actions and
      emotions has been proposed as a means to synchronize behaviour, thereby enhancing
      affiliation. Mimicry has long been thought to be reflexive, but it has recently
      been suggested that mimicry might also be motivationally driven. Here, we show
      during an economic bargaining game that automatic happy mimicry of those making
      unfair offers disappears. After the bargaining game, when the proposers have
      acquired either a fair or unfair reputation, we observe increased angry mimicry
      of proposers with an unfair reputation and decreased angry mimicry of fair
      proposers. These findings provide direct empirical evidence that non-conscious
      mimicry is modulated by fairness. We interpret the present results as reflecting
      that facial mimicry in women functions conditionally, dependent on situational
      demands.

PMID- 22648159
TI  - Am I seeing my hand? Visual appearance and knowledge of controllability both
      contribute to the visual capture of a person's own body.
AB  - When confronted with complex visual scenes in daily life, how do we know which
      visual information represents our own hand? We investigated the cues used to
      assign visual information to one's own hand. Wrist tendon vibration elicits an
      illusory sensation of wrist movement. The intensity of this illusion attenuates
      when the actual motionless hand is visually presented. Testing what kind of
      visual stimuli attenuate this illusion will elucidate factors contributing to
      visual detection of one's own hand. The illusion was reduced when a stationary
      object was shown, but only when participants knew it was controllable with their
      hands. In contrast, the visual image of their own hand attenuated the illusion
      even when participants knew that it was not controllable. We suggest that long
      term knowledge about the appearance of the body and short-term knowledge about
      controllability of a visual object are combined to robustly extract our own body
      from a visual scene.

PMID- 22648160
TI  - Prevalences of the Enterobacter cloacae complex and its phylogenetic derivatives
      in the nosocomial environment.
AB  - Despite the importance of the Enterobacter cloacae complex as a nosocomial
      pathogen, little is known about the relative contribution of its single species
      and genotypes to its pathogenicity. We studied here the relationship between
      phylogenetically related strains and clinical infection sites. A total of 196
      prospectively collected isolates of the E. cloacae complex were included in the
      study, comprising 67 blood culture isolates. Isolates were analyzed for clonality
      by pulsed-field gel electrophoresis (PFGE) and genetically assigned to their
      genotypes by partial hsp60 sequencing. Most isolates belonged in phylogenetic
      clade 1, with E. hormaechei being the most prevalent species. Notably, some
      genotypes and species, indeed, showed predilections to certain clinical
      specimens, whereas clinical outbreaks with members of the E. cloacae complex were
      rare. Our study stresses the need to identify alleged E. cloacae isolates on the
      subspecies level in clinical routine in order to obtain more insight into their
      distinct infectious potentials.

PMID- 22648161
TI  - Hole transfer dynamics from dye molecules to p-type NiO nanoparticles: effects of
      processing conditions.
AB  - Hole transfer dynamics of Atto647N sensitized p-type NiO nanoparticle (NP) thin
      films is investigated using both ensemble-averaged and single-molecule
      spectroscopy techniques. The rate of hole transfer is dependent on the processing
      conditions and is enhanced when the NiO is pre-annealed in air as compared to
      vacuum. This is possibly due to an upward shift of the valence band of the
      semiconductor and an increase in the free energy for hole transfer as more
      Ni(2)O(3) are formed in the presence of air. The stretched exponential
      fluorescence decay profile of Atto647N on NiO NP suggests the presence of a
      distribution of hole transfer rates. This is in agreement with the observed
      emission lifetime and intensity fluctuations and non-monoexponential fluorescence
      decays for individual Atto647N molecules on NiO NP films. A plausible explanation
      for the heterogeneous hole transfer rates is an inhomogeneous distribution of
      (defect) sites on the metal oxide due to the processing conditions and a
      fluctuation in the intermolecular interaction.

PMID- 22648162
TI  - A new look at the WHOQOL as health-related quality of life instrument among
      visually impaired people using Rasch analysis.
AB  - PURPOSE: To examine the psychometric characteristics of the World Health
      Organization quality of life instrument-modified Indian version (modified WHOQOL)
      and its subscales in adults with visual impairment (VI) using Rasch analysis.
      METHODS: Cross-sectional data were of people aged >=40 years with VI (n = 1,333)
      who responded to the modified WHOQOL in the Andhra Pradesh Eye Disease Study,
      India. Rasch analysis was used to explore the instrument and its subscales for
      key indices such as measurement precision by person separation reliability, PSR
      (i.e., discrimination between strata of participants' health-related QOL [HRQOL],
      recommended minimum value 0.8), unidimensionality (i.e., measurement of a single
      construct), and targeting (i.e., matching of item difficulty to participants'
      HRQOL). RESULTS: Rasch-guided iterative approach including category re
      organization to enable threshold ordering and item deletion to overcome
      multidimensionality resulted in a unidimensional 9-item WHOQOL and a 6-item level
      of independence (LOI) subscale with adequate PSR (0.81 and 0.82, respectively).
      Targeting was sub-optimal for both (-1.58 logits for WHOQOL and -2.55 logits for
      the subscale). Remaining subscales were dysfunctional. CONCLUSIONS: The WHOQOL
      and LOI subscale can be improved and shortened, and the Rasch-revised versions
      are likely to assess the HROQL of VI patients best because of their brevity,
      reliability, and unidimensionality.

PMID- 22648164
TI  - Validation of quantitative polymerase chain reaction methodology for monitoring
      DNA as a surrogate marker for species material contamination in porcine heparin.
AB  - Heparin is a widely used intravenous anticoagulant comprising of a very complex
      mixture of glycosaminoglycan chains, mainly derived from porcine intestinal
      mucosa. The species of origin and the absence of contaminants from other species
      are important determinants of the different physicochemical characteristics of
      heparin. They also determine the potential for introducing infectious and
      adventitious agents into heparin batches destined for medicinal use. We perform
      routine quantitative polymerase chain reaction (Q-PCR) release tests to confirm
      the quality of all crude heparin batches, including those used for the
      manufacture of enoxaparin sodium. Here we further demonstrate that the assessment
      of the DNA content in crude heparin is a good surrogate marker of contamination
      at the mucosa level. After spiking porcine mucosa with ovine mucosa and
      processing this material to form crude heparin, we were able to observe similar
      ratios of species-specific DNA in both the starting and end products. Experiments
      performed with 3,000 and 1,500 ppm contamination found these concentrations to be
      well above the detection limit for our assay of heparin batches. Additionally
      this Q-PCR method can be used to detect contamination in mucosa, thus providing a
      tool capable of monitoring for contaminants throughout the crude heparin
      manufacturing process. Q-PCR analysis of industrial crude heparin samples has
      confirmed over time the value of this method to assess the pure porcine origin of
      heparin.

PMID- 22648163
TI  - ANCA-associated glomerulonephritis/systemic vasculitis in childhood: clinical
      features-outcome.
AB  - BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated
      glomerulonephritis and systemic vasculitis (AAGNV) is uncommon in childhood.
      METHODS: This is a retrospective study of AAGNV cases diagnosed over a 13-year
      period in a tertiary pediatric nephrology department. RESULTS: Thirteen cases of
      AAGNV were identified: seven Wegener granulomatosis (WG) and six microscopic
      polyangiitis (MPA). Acute renal failure/nephrotic range proteinuria (NRP) was
      found in 77 % of the patients (4 with WG, all with MPA). Eleven (85 %) patients
      showed necrotizing glomerulonephritis (NGN), with >=50 % crescents identified in
      nine patients (69 %) (4 with WG, 5 with MPA). Treatment with methylprednisolone,
      cyclophosphamide and plasma exchange resulted in extra-renal remission and
      antibody reduction in all patients and renal function improvement/stabilization
      in 77 % of the patients. Three patients, all without oliguria at presentation and
      few sclerotic lesions, had normal renal function at follow-up. Chronic kidney
      disease (CKD) stages 2 and 3-4 were observed in four (WG) and three (MPA)
      patients, respectively. Three patients (23 %) developed end stage renal disease:
      two were MPA patients with severe presentation (markedly impaired glomerular
      filtration rate, oliguria, NRP, crescentic NGN, glomerular sclerosis) and one was
      a WG patient with extensive interstitial fibrosis/tubular atrophy. CONCLUSIONS:
      Severe renal involvement was more common in children with MPA than WG. Treatment
      with methylprednisolone, cyclophosphamide and plasma exchange induced extra-renal
      remission/serological response and renal function improvement/stabilization.
      Markedly decreased GFR, oliguria, NRP, and chronic glomerular lesions at
      presentation were predictors of poor outcome.

PMID- 22648165
TI  - Quantitative analysis of aberrant fatty acid composition of zebrafish hepatic
      lipids induced by organochlorine pesticide using stable isotope-coded
      transmethylation and gas chromatography-mass spectrometry.
AB  - Organochlorine pesticides have been extensively used worldwide for agricultural
      purposes. Due to their resistance to metabolism, a major public health concern
      has been raised. Aberrant hepatic lipid composition has been a hallmark of many
      liver diseases associated with exposure to various toxins and chemicals. And thus
      lots of efforts have been focused on the development of analytical techniques
      that can rapidly and quantitatively determine the changes in fatty acid
      composition of hepatic lipids. In this work, changes in fatty acid composition of
      hepatic lipids in response to DDT (dichlorodiphenyltrichloroethane) exposure were
      quantitatively analyzed by a gas chromatography-mass spectrometric approach based
      on stable isotope-coded transmethylation. It has been quantitatively demonstrated
      that polyunsaturated fatty acids including C20:3n3, C20:4n6, and C22:6n3 decrease
      in response to DDT exposure. However, saturated long chain fatty acids including
      C16:0, C18:0, as well as monounsaturated long chain fatty acid C18:1n9
      consistently increase in a DDT-concentration-dependent manner. In particular,
      much higher changes in the level of hepatic C16:0 and C18:0 for male fish were
      observed than that for female fish. These experimental results are in accordance
      with qualitative histopathological analysis that revealed liver morphological
      alterations. The stable isotope-coded mass spectrometric approach provides a
      reliable means for investigating hepatotoxicity associated with fatty acid
      synthesis, desaturation, mitochondrial beta-oxidation, and lipid mobilization. It
      should be useful in elucidation of hepatotoxic mechanisms and safety assessment
      of environmental toxins.

PMID- 22648166
TI  - Highly sensitive detection and discrimination of LR and YR microcystins based on
      protein phosphatases and an artificial neural network.
AB  - The inhibition characteristics of three different protein phosphatases by three
      microcystin (MC) variants--LR, YR, and RR--were studied. The corresponding K (I)
      for each enzyme-MC couple was calculated. The toxicity of MC varies in the
      following order: MC-LR > MC-YR > MC-RR. The sensitivity of the enzymes increased
      in the following order: mutant PP2A < mutant PP1 < natural PP2A. The best limit
      of detection obtained was 21.2 pM MC-LR using the most sensible enzyme. Methanol,
      ethanol, and acetonitrile up to 2 % (v/v) may be used in inhibition measurements.
      An artificial neural network (ANN) was used to discriminate two MC variants--LR
      and YR--using the differences in inhibition percentages measured with mutant PP1
      and natural PP2A. The ANN is able to analyze mixtures with concentrations ranging
      from 8 to 98 pM MC-LR and 31 to 373 pM MC-YR.

PMID- 22648167
TI  - Serum metabolomics as a novel diagnostic approach for disease: a systematic
      review.
AB  - Metabolomics is a promising "omics" field in systems biology; its objective is
      comprehensive analysis of low-molecular-weight endogenous metabolites in a
      biological sample. It could enable mapping of perturbations of early biochemical
      changes in diseases and hence provide an opportunity to develop predictive
      biomarkers that could result in earlier intervention and provide valuable
      insights into the mechanisms of diseases. Because of the possible discovery of
      clinically relevant biomarkers, metabolomics has potential advantages that
      routine approaches to clinical diagnosis do not. Monitoring specific metabolite
      levels in serum, the most commonly used biofluid in metabolomics, has become an
      important way of detecting the early stages of a disease. Serum is a readily
      accessible and informative biofluid, making it ideal for early detection of a
      wide range of diseases, and analysis of serum has several advantages over
      analysis of other biofluids. Metabolite profiles of serum can be regarded as
      important indicators of physiological and pathological states and may aid
      understanding of the mechanism of disease occurrence and progression on the
      metabolic level, and provide information enabling identification of early and
      differential metabolic markers of disease. Analysis of these crucial metabolites
      in serum has become important in monitoring the state of biological organisms and
      is widely used for diagnosis of disease. Emerging metabolomics will drive serum
      analysis, facilitate and improve the development of disease treatments, and
      provide great benefits for public health in the long-term.

PMID- 22648168
TI  - Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of
      cellular remodeling.
AB  - Cells rely on the coordinated regulation of lipid phosphoinositides and Rab
      GTPases to define membrane compartment fates along distinct trafficking routes.
      The family of disease-related myotubularin (MTM) phosphoinositide phosphatases
      includes catalytically inactive members, or pseudophosphatases, with poorly
      understood functions. We found that Drosophila MTM pseudophosphatase Sbf
      coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21
      GTPase activation in an endosomal pathway that controls macrophage remodeling.
      Sbf dynamically interacts with class II phosphatidylinositol 3-kinase and stably
      recruits Mtm to promote turnover of a PI(3)P subpool essential for endosomal
      trafficking. Sbf also functions as a guanine nucleotide exchange factor that
      promotes Rab21 GTPase activation associated with PI(3)P endosomes. Of importance,
      Sbf, Mtm, and Rab21 function together, along with Rab11-mediated endosomal
      trafficking, to control macrophage protrusion formation. This identifies Sbf as a
      critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal
      pathway and cortical control.

PMID- 22648169
TI  - Efficient secretion of small proteins in mammalian cells relies on Sec62
      dependent posttranslational translocation.
AB  - Mammalian cells secrete a large number of small proteins, but their mode of
      translocation into the endoplasmic reticulum is not fully understood.
      Cotranslational translocation was expected to be inefficient due to the small
      time window for signal sequence recognition by the signal recognition particle
      (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon
      component Sec62 by RNA interference, we found an alternate, Sec62-dependent
      translocation path in mammalian cells required for the efficient translocation of
      small proteins with N-terminal signal sequences. The Sec62-dependent
      translocation occurs posttranslationally via the Sec61 translocon and requires
      ATP. We classified preproteins into three groups: 1) those that comprise <=100
      amino acids are strongly dependent on Sec62 for efficient translocation; 2) those
      in the size range of 120-160 amino acids use the SRP pathway, albeit
      inefficiently, and therefore rely on Sec62 for efficient translocation; and 3)
      those larger than 160 amino acids depend on the SRP pathway to preserve a
      transient translocation competence independent of Sec62. Thus, unlike in yeast,
      the Sec62-dependent translocation pathway in mammalian cells serves mainly as a
      fail-safe mechanism to ensure efficient secretion of small proteins and provides
      cells with an opportunity to regulate secretion of small proteins independent of
      the SRP pathway.

PMID- 22648170
TI  - The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate
      integrin beta1 endocytosis.
AB  - Endocytic adaptor proteins facilitate cargo recruitment and clathrin-coated pit
      nucleation. The prototypical clathrin adaptor AP2 mediates cargo recruitment,
      maturation, and scission of the pit by binding cargo, clathrin, and accessory
      proteins, including the Eps-homology (EH) domain proteins Eps15 and intersectin.
      However, clathrin-mediated endocytosis of some cargoes proceeds efficiently in
      AP2-depleted cells. We found that Dab2, another endocytic adaptor, also binds to
      Eps15 and intersectin. Depletion of EH domain proteins altered the number and
      size of clathrin structures and impaired the endocytosis of the Dab2- and AP2
      dependent cargoes, integrin beta1 and transferrin receptor, respectively. To test
      the importance of Dab2 binding to EH domain proteins for endocytosis, we mutated
      the EH domain-binding sites. This mutant localized to clathrin structures with
      integrin beta1, AP2, and reduced amounts of Eps15. Of interest, although integrin
      beta1 endocytosis was impaired, transferrin receptor internalization was
      unaffected. Surprisingly, whereas clathrin structures contain both Dab2 and AP2,
      integrin beta1 and transferrin localize in separate pits. These data suggest that
      Dab2-mediated recruitment of EH domain proteins selectively drives the
      internalization of the Dab2 cargo, integrin beta1. We propose that adaptors may
      need to be bound to their cargo to regulate EH domain proteins and internalize
      efficiently.

PMID- 22648171
TI  - Kv2.1 cell surface clusters are insertion platforms for ion channel delivery to
      the plasma membrane.
AB  - Voltage-gated K(+) (Kv) channels regulate membrane potential in many cell types.
      Although the channel surface density and location must be well controlled, little
      is known about Kv channel delivery and retrieval on the cell surface. The Kv2.1
      channel localizes to micron-sized clusters in neurons and transfected human
      embryonic kidney (HEK) cells, where it is nonconducting. Because Kv2.1 is
      postulated to be involved in soluble N-ethylmaleimide-sensitive factor attachment
      protein receptor-mediated membrane fusion, we examined the hypothesis that these
      surface clusters are specialized platforms involved in membrane protein
      trafficking. Total internal reflection-based fluorescence recovery after
      photobleaching studies and quantum dot imaging of single Kv2.1 channels revealed
      that Kv2.1-containing vesicles deliver cargo at the Kv2.1 surface clusters in
      both transfected HEK cells and hippocampal neurons. More than 85% of cytoplasmic
      and recycling Kv2.1 channels was delivered to the cell surface at the cluster
      perimeter in both cell types. At least 85% of recycling Kv1.4, which, unlike
      Kv2.1, has a homogeneous surface distribution, is also delivered here. Actin
      depolymerization resulted in Kv2.1 exocytosis at cluster-free surface membrane.
      These results indicate that one nonconducting function of Kv2.1 is to form
      microdomains involved in membrane protein trafficking. This study is the first to
      identify stable cell surface platforms involved in ion channel trafficking.

PMID- 22648172
TI  - The function of p120 catenin in filopodial growth and synaptic vesicle clustering
      in neurons.
AB  - At the developing neuromuscular junction (NMJ), physical contact between motor
      axons and muscle cells initiates presynaptic and postsynaptic differentiation.
      Using Xenopus nerve-muscle cocultures, we previously showed that innervating
      axons induced muscle filopodia (myopodia), which facilitated interactions between
      the synaptic partners and promoted NMJ formation. The myopodia were generated by
      nerve-released signals through muscle p120 catenin (p120ctn), a protein of the
      cadherin complex that modulates the activity of Rho GTPases. Because axons also
      extend filopodia that mediate early nerve-muscle interactions, here we test
      p120ctn's function in the assembly of these presynaptic processes. Overexpression
      of wild-type p120ctn in Xenopus spinal neurons leads to an increase in filopodial
      growth and synaptic vesicle (SV) clustering along axons, whereas the development
      of these specializations is inhibited following the expression of a p120ctn
      mutant lacking sequences important for regulating Rho GTPases. The p120ctn mutant
      also inhibits the induction of axonal filopodia and SV clusters by basic
      fibroblast growth factor, a muscle-derived molecule that triggers presynaptic
      differentiation. Of importance, introduction of the p120ctn mutant into neurons
      hinders NMJ formation, which is observed as a reduction in the accumulation of
      acetylcholine receptors at innervation sites in muscle. Our results suggest that
      p120ctn signaling in motor neurons promotes nerve-muscle interaction and NMJ
      assembly.

PMID- 22648174
TI  - Dietary supplementation with methyl donors reduces fatty liver and modifies the
      fatty acid synthase DNA methylation profile in rats fed an obesogenic diet.
AB  - Non-alcoholic fatty liver disease (NAFLD) is one of the first hepatic
      manifestations of metabolic syndrome, whose progression can lead to cirrhosis and
      hepatic carcinoma. Interestingly, methyl donor supplementation could improve
      obesogenic diet-induced hepatic triglyceride accumulation. The aim of this
      research is to describe methyl donor effects on a high-fat-sucrose (HFS) diet in
      both sexes and epigenetic changes induced on fatty acid synthase (FASN) promoter
      methylation pattern as well as gene expression of NAFLD key metabolic genes.
      Twenty-four male and 28 female Wistar rats were assigned to three dietary groups:
      control, HFS, and HFS supplemented with methyl donors (choline, betaine, vitamin
      B12, and folic acid). After 8 weeks of treatment, somatic, biochemical, mRNA, and
      epigenetic measurements were performed. Rats fed the HFS diet presented an
      overweight phenotype and alterations in plasma biochemical measurements. Methyl
      donor supplementation reverted the HFS-diet-induced hepatic triglyceride
      accumulation. Analysis of FASN promoter cytosine methylation showed changes in
      both sexes due to the obesogenic diet at -1,096, -780, -778, and -774 CpG sites
      with respect to the transcriptional start site. Methyl donor supplementation
      modified DNA methylation at -852, -833, -829, -743, and -733 CpGs depending on
      the sex. RT-PCR analysis confirmed that FASN expression tended to be altered in
      males. Our findings reinforce the hypothesis that methyl donor supplementation
      can prevent hepatic triglyceride accumulation induced by obesogenic diets in both
      sexes. Changes in liver gene expression profile and epigenetic-mediated
      mechanisms related to FASN DNA hypermethylation could be involved in methyl donor
      induced NAFLD improvement.

PMID- 22648175
TI  - A comparative evaluation of ablations produced by high-frequency coagulation-,
      argon plasma coagulation-, and cryotherapy devices in porcine liver.
AB  - INTRODUCTION: Hepatic resection is the only curative treatment option for primary
      or metastatic malignancies of the liver. Although R1 resections can also lead to
      prolonged survival, the main surgical goal is complete tumor resection (R0). To
      achieve this, additional treatment of the resection margin with ablation devices
      is discussed. Using a porcine in vivo model, we therefore analyzed the effect of
      different ablation devices on depth and completeness of hepatic parenchymal cell
      destruction. METHODS: Swabian-Hall strain pigs underwent ablation on the surface
      of the right, middle, or left liver lobe using seven different types of high
      frequency (HF)-, cryotherapy (Cryo)-, or argon plasma coagulation (APC) devices.
      Penetration depth and volume were analyzed from histological sections. Severity
      of parenchymal cell destruction was assessed by a histomorphological score.
      RESULTS: The greatest penetration depth was achieved with Cryo (10.4 +/- 1.7 mm),
      whereas HF and APC exhibited a smaller penetration depth. However, HF and APC
      compared to Cryo achieved complete destruction of the intralobular architecture
      and hepatocellular morphology depending on the application time and the adjusted
      power. CONCLUSION: HF, APC, and Cryo applied to the liver surface induce
      different parenchymal penetration depth and cell destruction. HF and APC are
      considered to be standard surgical instruments and therefore recommended as
      standard treatment, whereas Cryo may be used only if particularly deep
      penetration is required.

PMID- 22648177
TI  - Myofascial pelvic pain.
AB  - Myofascial pelvic pain is fraught with many unknowns. Is it the organs of the
      pelvis, is it the muscles of the pelvis, or is the origin of the pelvic pain from
      an extrapelvic muscle? Is there a single source or multiple? In this state of
      confusion what is the best way to manage the many symptoms that can be associated
      with myofascial pelvic pain. This article reviews current studies that attempt to
      answer some of these questions. More questions seem to develop as each study
      presents its findings.

PMID- 22648178
TI  - Hormonal contraception and migraine: clinical considerations.
AB  - Migraine is highly prevalent in women, particularly in the reproductive years
      when contraception may be needed. Preventive strategies are known to be
      underutilized for migraine. Women of reproductive age may not only benefit from
      the use of hormonal contraceptives for contraception, but also for the purpose of
      reducing the burden of menstrual-related migraine. Although migraine is
      associated with an increased risk of stroke, the use of low-dose hormonal
      contraceptives in otherwise healthy women does not appear to confer additional
      risk.

PMID- 22648179
TI  - A phase 1 study of weekly dosing of trastuzumab emtansine (T-DM1) in patients
      with advanced human epidermal growth factor 2-positive breast cancer.
AB  - BACKGROUND: We conducted a phase 1, multicenter, open-label, dose-escalation
      study (TDM3569g) to assess the safety, tolerability, and pharmacokinetics of
      single-agent trastuzumab emtansine (T-DM1) administered weekly and once every 3
      weeks in patients with HER2-positive metastatic breast cancer previously treated
      with trastuzumab. The weekly dose results are described here. METHODS: Patients
      were administered escalating doses of T-DM1 weekly, starting at 1.2 mg/kg.
      Additional patients were enrolled at the maximum tolerated dose (MTD) to better
      characterize tolerability and pharmacokinetics. RESULTS: Twenty-eight patients
      received weekly T-DM1, and the MTD was determined to be 2.4 mg/kg. In general, T
      DM1 was well tolerated, requiring few dose modifications or discontinuations
      because of adverse events (AEs). Grade >= 3 AEs were reported in 19 patients
      (67.9%); treatment-related AEs occurred in 25 (89.3%) patients. Exposure to
      weekly T-DM1 was dose-proportional at >= 1.2 mg/kg, and accumulation of T-DM1 and
      total trastuzumab was observed. Objective partial tumor responses were reported
      in 13 (46.4%) patients; the median duration of response was 18.6 months, and the
      6-month clinical benefit rate was 57.1%. CONCLUSION: The results suggest that a
      weekly dose of T-DM1 2.4 mg/kg has antitumor activity and is well tolerated in
      patients with HER2-positive metastatic breast cancer.

PMID- 22648180
TI  - Association of variants in genes involved in environmental chemical metabolism
      and risk of cryptorchidism and hypospadias.
AB  - We hypothesized that single-nucleotide polymorphisms (SNPs) of genes involved in
      environmental endocrine disruptors (EEDs) metabolism might influence the risk of
      male genital malformations. In this study, we explored for association between
      384 SNPs in 15 genes (AHR, AHRR, ARNT, ARNT2, NR1I2, RXRA, RXRB, RXRG, CYP1A1,
      CYP1A2, CYP1B1, CYP2B6, CYP3A4, CYP17A1 and CYP19A1) and risk of cryptorchidism
      (CO) and hypospadias (HS) in 334 Japanese (JPN) males (141 controls, 95 CO and 98
      HS) and 187 Italian (ITA) males (129 controls and 58 CO). In the JPN study group,
      five SNPs from ARNT2 (rs2278705 and rs5000770), CYP1A2 (rs2069521), CYP17A1
      (rs4919686) and NR1I2 (rs2472680) were significantly associated at both allelic
      and genotypic levels with risk of at least one genital malformation phenotype. In
      the ITA study group, two SNPs in AHR (rs3757824) and ARNT2 (rs1020397) were
      significantly associated with risk of CO. Interaction analysis of the positive
      SNPs using multifactor dimensionality reduction demonstrated that synergistic
      interaction between rs2472680, rs4919686 and rs5000770 had 62.81% prediction
      accuracy for CO (P=0.011) and that between rs2069521 and rs2278705 had 69.98%
      prediction accuracy for HS (P=0.001) in JPN population. In a combined analysis of
      JPN and ITA population, the most significant multi-locus association was observed
      between rs5000770 and rs3757824, which had 65.70% prediction accuracy for CO
      (P=0.055). Our findings indicate that genetic polymorphisms in genes involved in
      EED metabolism are associated with risk of CO and HS.

PMID- 22648181
TI  - A powerful parent-of-origin effects test for qualitative traits incorporating
      control children in nuclear families.
AB  - Genomic imprinting is an important epigenetic phenomenon in studying complex
      traits and has generally been examined by detecting parent-of-origin effects of
      alleles. The parental-asymmetry test (PAT) based on nuclear families with both
      parents and its extensions to deal with missing parental genotypes is simple and
      powerful for such a task. However, these methods only use case (affected)
      children in nuclear families and thus do not make full use of information on
      control (unaffected) children, if available, in these families. In this article,
      we propose a novel parent-of-origin effects test C-PATu (the combined test of
      PATu and 1-PATu) by using both the control and case children in nuclear families
      with one or both parents. C-PATu is essentially a weighted framework, in which
      the test based on all the control children and their parents and that based on
      all the case children and their parents are weighted according to the population
      disease prevalence. Simulation results demonstrate that the proposed tests
      control the size well under no parent-of-origin effects and using additional
      information from control children improves the power of the tests under the
      imprinting alternative. Application of C-PATu to a Framingham Heart Study data
      set further shows the feasibility in practical application of the test.

PMID- 22648182
TI  - Screening of genes involved in chromosome segregation during meiosis I: in vitro
      gene transfer to mouse fetal oocytes.
AB  - The events that take place during the prophase of meiosis I are essential for the
      correct segregation of homologous chromosomes. Defects in these processes likely
      contribute to infertility or recurrent pregnancy loss in humans. To screen for
      candidate genes for reproductive failure due to meiotic defects, we have analyzed
      the gene expression patterns in fetal, neonatal and adult gonads of both male and
      female mice by microarray and thereby identified 241 genes that are expressed
      specifically during prophase of meiosis I. Combined with our previous data
      obtained from developing spermatocytes, a total of 99 genes were identified that
      are upregulated in early prophase I. We confirmed the meiotic prophase I-specific
      expression of these genes using qRT-PCR. To further screen this panel for
      candidate genes that fulfill important roles in homologous pairing, synapsis and
      recombination, we established a gene transfer system for prophase I oocytes in
      combination with in vitro organ culture of ovaries, and successfully determined
      the localization of the selected genes. This gene set can thus serve as a
      resource for targeted sequence analysis via next-generation sequencing to
      identify the genes associated with human reproduction failure due to meiotic
      defects.

PMID- 22648183
TI  - An abundance of population-specific monomorphic SNPs may or may not be
      meaningful: a commentary on differences in allele frequencies of familial
      hypercholesterolemia SNPs in the Malaysian population.

PMID- 22648185
TI  - Effects of an Asian-specific nonsynonymous EDAR variant on multiple dental
      traits.
AB  - Dental morphology is highly diverse among individuals and between human
      populations. Although it is thought that genetic factors mainly determine common
      dental variations, only a few such genetic factors have been identified. One
      study demonstrated that a nonsynonymous single-nucleotide polymorphism (370V/A,
      rs3827760) in the ectodysplasin A receptor gene (EDAR) is associated with
      shoveling and double-shoveling grades of upper first incisors and tooth crown
      size. Here, we examined the association of EDAR 370V/A with several dental
      characters in Korean and Japanese subjects. A meta-analysis that combined
      analyses of Korean and Japanese subjects revealed that the Asian-specific 370A
      allele is associated with an increase in the grades of shoveling and double
      shoveling, as previously found. We also showed a highly significant association
      between EDAR 370V/A genotype and crown size, especially mesiodistal diameters of
      anterior teeth. Moreover, we found that the 370A allele was associated with the
      presence of hypoconulids of lower second molars. These results indicated that the
      EDAR polymorphism is responsible, in part, for the Sinodonty and Sundadonty
      dichotomy in Asian populations, and clearly demonstrated that the EDAR
      polymorphism has pleiotropic effects on tooth morphology. As the 370A allele is
      known to be a most likely target of positive selection in Asian populations, some
      phenotypes associated with the variant may be 'hitchhiking phenotypes', while
      others may be actual targets of selection.

PMID- 22648184
TI  - Hirschsprung's disease and variants in genes that regulate enteric neural crest
      cell proliferation, migration and differentiation.
AB  - Hirschsprung's disease (HSCR) results from failed colonization of the embryonic
      gut by enteric neural crest cells (ENCCs); colonization requires RET proto
      oncogene (RET) signaling. We sequenced RET to identify coding and splice-site
      variants in a population-based case group and we tested for associations between
      HSCR and common variants in RET and candidate genes (ASCL1, homeobox B5 (HOXB5),
      L1 cell adhesion molecule (L1CAM), paired-like homeobox 2b (PHOX2B), PROK1 and
      PROKR1) chosen because they are involved in ENCC proliferation, migration and
      differentiation in animal models. We conducted a nested case-control study of 304
      HSCR cases and 1215 controls. Among 38 (12.5%) cases with 34 RET coding and
      splice-site variants, 18 variants were previously unreported. We confirmed
      associations with common variants in HOXB5 and PHOX2B but the associations with
      variants in ASCL1, L1CAM and PROK1 were not significant after multiple
      comparisons adjustment. RET variants were strongly associated with HSCR (P-values
      between 10(-3) and 10(-31)) but this differed by race/ethnicity: associations
      were absent in African-Americans. Our population-based study not only identified
      novel RET variants in HSCR cases, it showed that common RET variants may not
      contribute to HSCR in all race/ethnic groups. The findings for HOXB5 and PHOX2B
      provide supportive evidence that genes regulating ENCC proliferation, migration
      and differentiation could be risk factors for HSCR.

PMID- 22648187
TI  - Ostomy creation in neonates with acute abdominal disease: friend or foe?
AB  - BACKGROUND: An ostomy seems a safe alternative in neonates with an acute abdomen
      when immediate restoration of bowel continuity is deemed undesirable. Faced with
      several complications in our center, and the feeling we are not the only center
      with these complications, we decided to assess the rate and type of complications
      after both ostomy creation and closure. METHODS: All data regarding neonates (<30
      days of age) who underwent a laparotomy for a suspected abdominal emergency in
      the period 2000 to 2010 were retrospectively analyzed. These data included
      demographics such as gender, gestational age, and birth weight. Disease etiology
      was defined and various features of the enterostomy were analyzed. These features
      included type, location, time to ostomy take down, and complications and
      mortality directly related to both creation and closure of the ostomy. RESULTS: A
      total of 155 patients who underwent a laparotomy for suspect acute abdomen were
      identified. Median gestational age was 33 weeks (range 25 to 40) and median birth
      weight was 1926 g (range 560 to 4380). Median age at laparotomy was 8 days (range
      0 to 30). Indications for surgery were necrotizing enterocolitis (n = 38),
      spontaneous intestinal perforation (n = 11), intestinal atresia (n = 9) or
      obstruction (n = 5), and volvulus (n = 4). An ostomy was created in 67 patients
      (67/155: 43%): 38 boys and 29 girls. There were 8 jejuno-, 49 ileo-, and 10
      colostomies created. In almost all cases (94%), a mucous fistula was also
      constructed.In 23 patients (23/67: 34%) ostomy-related complications occurred.
      Most frequent were high output ostomy (n = 10) and necrosis of the enterostomy (n
      = 7). Due to either one of the complications, nine patients (9/67: 13%) needed a
      reoperation.In this study, 11 patients died before ostomy closure could occur. In
      53 patients, the ostomy was closed after a median of 107 days (range 4 to
      299).After ostomy closure, complications occurred in 13 cases (13/53: 25%). Seven
      patients (7/53: 13%) needed another reoperation because of anastomotic leakage (n
      = 4), adhesions (n = 2), or incisional hernia (n = 1). There was no closure
      related mortality. CONCLUSION: Although creating a temporary ostomy in newborns
      is preferable in certain situations, there is a considerable occurrence of
      complications and reoperations.

PMID- 22648186
TI  - Comprehensive evaluation of imputation performance in African Americans.
AB  - Imputation of genome-wide single-nucleotide polymorphism (SNP) arrays to a larger
      known reference panel of SNPs has become a standard and an essential part of
      genome-wide association studies. However, little is known about the behavior of
      imputation in African Americans with respect to the different imputation
      algorithms, the reference population(s) and the reference SNP panels used. Genome
      wide SNP data (Affymetrix 6.0) from 3207 African American samples in the
      Atherosclerosis Risk in Communities Study (ARIC) was used to systematically
      evaluate imputation quality and yield. Imputation was performed with the
      imputation algorithms MACH, IMPUTE and BEAGLE using several combinations of three
      reference panels of HapMap III (ASW, YRI and CEU) and 1000 Genomes Project (pilot
      1 YRI June 2010 release, EUR and AFR August 2010 and June 2011 releases) panels
      with SNP data on chromosomes 18, 20 and 22. About 10% of the directly genotyped
      SNPs from each chromosome were masked, and SNPs common between the reference
      panels were used for evaluating the imputation quality using two statistical
      metrics-concordance accuracy and Cohen's kappa (kappa) coefficient. The
      dependencies of these metrics on the minor allele frequencies (MAF) and specific
      genotype categories (minor allele homozygotes, heterozygotes and major allele
      homozygotes) were thoroughly investigated to determine the best panel and method
      for imputation in African Americans. In addition, the power to detect imputed
      SNPs associated with simulated phenotypes was studied using the mean genotype of
      each masked SNP in the imputed data. Our results indicate that the genotype
      concordances after stratification into each genotype category and Cohen's kappa
      coefficient are considerably better equipped to differentiate imputation
      performance compared with the traditionally used total concordance statistic, and
      both statistics improved with increasing MAF irrespective of the imputation
      method. We also find that both MACH and IMPUTE performed equally well and
      consistently better than BEAGLE irrespective of the reference panel used. Of the
      various combinations of reference panels, for both HapMap III and 1000 Genomes
      Project reference panels, the multi-ethnic panels had better imputation accuracy
      than those containing only single ethnic samples. The most recent 1000 Genomes
      Project release June 2011 had substantially higher number of imputed SNPs than
      HapMap III and performed as well or better than the best combined HapMap III
      reference panels and previous releases of the 1000 Genomes Project.

PMID- 22648188
TI  - Efficacy of pelvic floor muscle training for the treatment of fecal incontinence
      after Soave procedure for Hirschsprung disease.
AB  - OBJECTIVE: The main objective of this study is to evaluate the efficacy of pelvic
      floor muscle exercise for the treatment of fecal incontinence after Soave
      procedure for Hirschsprung disease (HD). METHODS: A case series study was
      performed in 24 incontinent children after Soave pull-through surgery for HD. Out
      of the 24 patients, 16 patients (training group) received pelvic floor muscle
      training while the other 8 patients (control group) did not receive further
      treatment. For children who received pelvic floor muscle training, biofeedback
      treatment was given for 2 weeks in hospital and they were then instructed to
      carry out pelvic floor muscle exercise at home. At the baseline and after 1 year
      of training, anorectal manometry was performed to measure resting anal canal
      pressure, squeeze pressure, and rectal sensation. Efficacy of pelvic floor muscle
      exercise for the treatment of postoperative fecal incontinence was evaluated by
      the difference between baseline and 1-year follow-up values. At the baseline, the
      characteristics of the incontinent children were also compared with 18 children
      who were performed Soave operation for HD and had normal anal function. RESULTS:
      Lower resting anal canal pressure distinguished the incontinent children from the
      continent ones. Resting pressure of the incontinent children was significantly
      improved by pelvic floor muscle exercise: the baseline and 1-year follow-up
      values of the treatment group were 18.6 +/- 6.2 and 35.4 +/- 8.7 mm Hg,
      respectively. Squeeze pressure and clinical outcomes were also improved after the
      pelvic floor muscle training: only 3 out of the 16 patients had occasional
      soiling after the training. No significant changes in clinical outcome and
      manometry measurements were observed in the control group. CONCLUSIONS: The
      damage of internal anal sphincter might be one of the causes of fecal
      incontinence after Soave procedure. The damage of internal anal sphincter could
      be caused by lower level of dissection, vigorous anal dilation, and excessive
      anal canal traction during operation. Pelvic floor muscle training is one
      procedure of choice to treat this complaint.

PMID- 22648189
TI  - Jejunal pedicle graft reconstruction of the esophagus in a child with tracheal
      agenesis.

PMID- 22648190
TI  - Epidural air in child with spontaneous pneumomediastinum.

PMID- 22648191
TI  - A rare association of congenital lumbar hernia and giant congenital nevus.

PMID- 22648192
TI  - Juvenile psammomatoid ossifying fibroma of the forehead, radical resection, and
      defect coverage with a hydroxyl-apatite composite-a case report.

PMID- 22648193
TI  - Primary reconstruction of fingernail injuries in children with split-thickness
      nail bed grafts.
AB  - INTRODUCTION: Failure to detect and treat partial or complete avulsions of the
      nail bed may lead to severe nail deformity that predisposes to repeat injuries
      and is cosmetically inacceptable. Treatment of these injuries with split
      thickness nail bed grafts (STNBGs) is controversial and no pediatric series has
      been published. METHODS: A retrospective, single center case series of nine
      fingers with complex nail bed injuries that were reconstructed primarily with
      STNBGs was performed. Surgical outcome and patient satisfaction were assessed.
      RESULTS: For six nail bed reconstructions, the nail bed graft was harvested from
      the injured finger, and for the remaining three from the great toe. Harvesting of
      the great toe's nail bed could be performed without removal of the nail plate by
      only lifting it up distally. Insufficient vascularization required primary flap
      coverage in six cases with three Moberg flaps, two palmar V-Y flaps, and one
      thenar flap. No flap was lost and all nail bed grafts had a 100% take. Only one
      patient required reoperation due to a hook- and split-nail deformity. All other
      patients were satisfied or very satisfied and the surgical outcome was least
      satisfactory in all but two patients. CONCLUSIONS: Primary reconstruction of
      complex nail bed injuries with STNBGs usually gives good cosmetic and functional
      results in children and prevents secondary nail growth disturbances reliably.

PMID- 22648194
TI  - Pediatric Crohn disease presenting as appendicitis: differentiating features from
      typical appendicitis.
AB  - BACKGROUND: The initial presentation of Crohn disease (CD) may mimic acute
      appendicitis, and preoperative clues may aid in recognizing patients at risk for
      CD. METHODS: A retrospective case control study of patients presenting over 10
      years compared control patients with appendicitis versus patients presenting with
      appendicitis who ultimately developed CD. We matched 10 patients of the same age,
      gender, and perforated versus nonperforated appendicitis status for each of the
      CD patients. Demographic, laboratory, and clinical data were compared.
      Additionally, appendectomy specimens of CD patients were genotyped for common
      NOD2 (nucleotide-binding oligomerization domain-containing protein 2) mutations.
      RESULTS: Of 2718 patients treated for appendicitis, 8 subsequently developed CD.
      Compared to the matched controls, CD patients were found to have lower hemoglobin
      (10.4 + 1.0 vs. 13.3 + 0.2, p < 0.0001) and mean corpuscular volume (MCV) (72.5 +
      3.4 vs. 84.1 + 0.5, p < 0.0001) values, and higher platelets values (444.8 + 42.2
      vs. 275.6 + 8.0, p < 0.0001) at initial presentation. Anthropometric z-scores,
      length of stay, and antibiotic therapy duration did not significantly differ
      between groups. The NOD2 mutation frequency (25%) was consistent with the
      currently described CD population. CONCLUSIONS: Preoperative findings of a low
      hemoglobin level and MCV count, and a high platelet count in a child presenting
      with appendicitis warrant further evaluation for CD, as prompt diagnosis allows
      for optimal treatment and quality of life for these patients.

PMID- 22648195
TI  - Pure ovarian tuberculosis as a surprising cause of adnexal mass in an adolescent.

PMID- 22648196
TI  - Gastric transposition after duodenoduodenostomy in infants with combined
      esophageal and duodenal atresia-report of three cases.

PMID- 22648197
TI  - Ureteral replacement with appendix in a pediatric group: a report of two cases
      and review of the literature.

PMID- 22648198
TI  - Capsule endoscopy guided bowel resection for obscure gastrointestinal hemorrhage.

PMID- 22648199
TI  - Elastic stable intramedullary nailing (ESIN) of pediatric metacarpal fractures:
      experiences with 66 cases.
AB  - INTRODUCTION: Elastic stable intramedullary nailing (ESIN) is the first-choice
      surgical technique for stabilizing various pediatric diaphyseal and selected
      metaphyseal fractures of the long bones. This technique has increasingly been
      applied in fractures of the small bones. Here, we report experiences with ESIN in
      displaced fractures of the metacarpals in children. PATIENTS AND METHODS:
      Retrospective data analysis of metacarpal fractures in children stabilized by
      ESIN in three pediatric trauma centers between 2003 and 2009. Indication for
      intervention was total displacement or axial deviation >10 degrees in the frontal
      plane and/or >30 degrees in the sagittal view. RESULTS: A total of 66 cases of
      metacarpal fractures (51 right hand and 12 left hand) treated by ESIN were found
      in 63 children (mean age 13.3 years; range 4.0 to 16.1) over the study period. Of
      these, 55 fractures affected metacarpal 5, 6 fractures affected metacarpal 4, 3
      fractures affected metacarpal 1, and 2 fractures occurred at metacarpal 2. Mean
      operating time was 21 minutes (range 5 to 54), titanium elastic nails were used
      with a diameter of 1.5 mm (n = 23), 2.0 mm (n = 42), and 2.5 mm (n = 1). Single
      ESIN implantation was performed in 63 cases; in 3 cases, two nails were
      implanted. Eleven patients received additional immobilization due to nondisplaced
      additional fractures of the phalanx (n = 2) or for analgetic treatment (n = 9).
      Five complications were registered (7.6%). In two cases recurrent fracture
      dislocation occurred, one of them requiring revision of the osteosynthesis. In
      other two cases irritation of the extensor tendons occurred, one of them
      requiring secondary tendon plasty. One persisting cutaneous hyposensibility after
      ESIN of a metacarpal 5 fracture was reported. All fractures healed uneventfully
      and metal removal was performed after a mean of 92 days (range 31 to 104). After
      a mean follow-up of 26 months (range 2 to 74), all patients had full range of
      movement and cosmetic results were described as good and satisfactory by all
      patients. CONCLUSION: ESIN of the metacarpals is a safe, minimally invasive, and
      technically easy option in displaced fractures that warrant surgical intervention
      achieving excellent long-term results. Complications occurred when technical
      aspects to obtain stability were neglected or tendons and nerves of the hand had
      been injured. Stabilizing fractures of metacarpal 1 is technically challenging
      when compared with fractures of metacarpals 2 to 5.

PMID- 22648200
TI  - Effects of parenting and deviant peers on early to mid-adolescent conduct
      problems.
AB  - We investigated the influence of effective parenting behaviors (father and mother
      reports) and deviant peer association (adolescent reports) on subsequent young
      adolescent conduct problems (teacher reports) during grades 7-9, using structural
      equation modeling. Data were from a sample of 226 rural adolescents (n = 112
      boys; n = 107 girls; n = 7 gender unknown), their parents, and teachers. Both
      effective parenting and association with deviant peers influenced later conduct
      problems; however, the pattern of influence varied across time and between
      fathers and mothers, with complex patterns of interactions between effective
      parenting and peer deviance. From seventh to eighth grade, effective parenting by
      both mothers and fathers buffered the effect of higher levels of peer deviance on
      conduct problems across adolescent gender. From eighth to ninth grade (i.e.,
      transition into high school), fathers' effective parenting buffered the effects
      of deviant peer association on their daughters' conduct problems, whereas both
      fathers' and mothers' influence was stronger for sons when deviant peer
      associations were lower. Analyses also evaluated bi-directional longitudinal
      effects among adolescents, parents, and peers. Although varying by parent and
      adolescent gender or adolescent age, results generally supported the protective
      effects of parenting on their children's conduct problems during early to mid
      adolescence.

PMID- 22648202
TI  - Low-fat dairy, but not whole-/high-fat dairy, consumption is related with higher
      serum adiponectin levels in apparently healthy adults.
AB  - PURPOSE: Although previous studies suggested that higher low-fat dairy
      consumption lower the risk of type 2 diabetes, the mediating factors are not well
      understood. Higher baseline adiponectin levels are related with a lower risk of
      type 2 diabetes. This study evaluated whether low-fat dairy is related with
      adiponectin in apparently healthy adults. METHODS: We investigated a cross
      sectional (n = 938) and one-year longitudinal (n = 759) relationship between low
      fat and whole-/high-fat dairy (both including cow's milk and yogurt) and
      adiponectin. Dairy consumption was assessed with a validated food frequency
      questionnaire. Serum adiponectin was measured by using a specific sandwich enzyme
      linked immunosorbent assay. RESULTS: In the cross-sectional analysis, the
      geometric means (95 % confidence intervals [95 % CIs]) of log-transformed
      adiponectin related with the low-fat dairy categories were 7.27 (6.80-7.77) for
      the lowest category, 7.67 (7.09-8.31) for the middle category, and 8.40 (7.73
      9.13) for the highest category (p < 0.001) after adjustment for potential
      confounders (including all lifestyle factors). In the longitudinal analysis,
      repeated-measures ANCOVA adjusted for confounding factors showed a significant
      time-by-categories (categories of low-fat dairy) interaction in the change of
      adiponectin. In contrast, no significant relationship was found between the whole
      /high-fat dairy categories and adiponectin. CONCLUSIONS: This study has shown
      that higher consumption of low-fat dairy, but not of whole-/high-fat dairy, is
      related with higher levels of adiponectin and with the change of adiponectin
      level at the one-year follow-up. These results suggest that the consumption of
      low-fat dairy may have a beneficial effect on serum adiponectin levels.

PMID- 22648203
TI  - Exploring the thermodynamic derivatives of the structure factor of dense protein
      solutions.
AB  - Using small-angle X-ray scattering data of concentrated solutions of the protein
      lysozyme taken at different pressures and temperatures, the isothermal pressure
      derivative and the isobaric temperature derivative of the structure factor S(q)
      were determined. The pressure derivative of S(q) allows us to test various models
      for the triplet correlation function g(3). Significant differences were found in
      comparison to simple liquids reflecting the more complex interaction potential in
      dense protein solutions.

PMID- 22648205
TI  - Chemotherapy in patients with advanced pancreatic cancer: too close to death?
AB  - PURPOSE: We evaluated the attitude in using chemotherapy near the end of life in
      advanced pancreatic adenocarcinoma (PAC). Clinical and laboratory parameters
      recorded at last chemotherapy administration were analyzed, in order to identify
      risk factors for imminent death. METHODS: Retrospective analysis of patients who
      underwent at least one line of palliative chemotherapy was made. Data concerning
      chemotherapy (regimens, lines, and date of last administration) were collected.
      Clinical and laboratory factors recorded at last chemotherapy administration
      were: performance status, presence of ascites, hemoglobin, white blood cell
      (WBC), platelets, total bilirubin, albumin, LDH, C-reactive protein (C-rp), and
      Ca 19.9. RESULTS: We analyzed 231 patients: males/females, 53/47 %;
      metastatic/locally advanced disease, 80/20 %; and median age, 66 years (range 32
      85). All patients died due to disease progression. Median overall survival was
      6.1 months (95 % CI 5.1-7.2). At the last chemotherapy delivery, performance
      status was 0-1 in 37 % and 2 in 63 %. Fifty-nine percent of patients received one
      chemotherapy line, while 32, 8, and 1 % had second-, third-, and fourth line,
      respectively. The interval between last chemotherapy administration and death was
      <4 weeks in 24 %, >=4-12 in 47 %, and >12 in 29 %. Median survival from last
      chemotherapy to death was 7.5 weeks (95 % CI 6.7-8.4). In a univariate analysis,
      ascites, elevated WBC, bilirubin, LDH, C-rp and Ca 19.9, and reduced albumin were
      found to predict shorter survival; however, none of them remained significant in
      a multivariate analysis. CONCLUSIONS: A significant proportion of patients with
      advanced PAC received chemotherapy within the last month of life. The clinical
      and laboratory parameters recorded at last chemotherapy delivery did not predict
      shorter survival.

PMID- 22648206
TI  - Direct and maternal (co)variance components, genetic parameters, and annual
      trends for growth traits of Makooei sheep in Iran.
AB  - Genetic parameters and genetic trends for birth weight (BW), weaning weight (WW),
      6-month weight (6MW), and yearling weight (YW) traits were estimated by using
      records of 5,634 Makooei lambs, descendants of 289 sires and 1,726 dams, born
      between 1996 and 2009 at the Makooei sheep breeding station, West Azerbaijan,
      Iran. The (co)variance components were estimated with different animal models
      using a restricted maximum likelihood procedure and the most appropriate model
      for each trait was determined by Akaike's Information Criterion. Breeding values
      of animals were predicted with best linear unbiased prediction methodology under
      multi-trait animal models and genetic trends were estimated by regression mean
      breeding values on birth year. The most appropriate model for BW was a model
      including direct and maternal genetic effects, regardless of their covariance.
      The model for WW and 6MW included direct additive genetic effects. The model for
      YW included direct genetic effects only. Direct heritabilities based on the best
      model were estimated 0.15 +/- 0.04, 0.16 +/- 0.03, 0.21 +/- 0.04, and 0.22 +/-
      0.06 for BW, WW, 6MW, and YW, respectively, and maternal heritability obtained
      0.08 +/- 0.02 for BW. Genetic correlations among the traits were positive and
      varied from 0.28 for BW-YW to 0.66 for BW-WW and phenotypic correlations were
      generally lower than the genetic correlations. Genetic trends were 8.1 +/- 2,
      67.4 +/- 5, 38.7 +/- 4, and 47.6 +/- 6 g per year for BW, WW, 6MW, and YW,
      respectively.

PMID- 22648204
TI  - Frontoparietal involvement in passively guided shape and length discrimination: a
      comparison between subcortical stroke patients and healthy controls.
AB  - Fifty to 85 % of patients with sensorimotor hemiparesis following stroke
      encounter impaired tactile processing and proprioception. Sensory feedback is,
      however, paramount for motor recovery. Sensory feedback through passively guided
      somatosensory discrimination exercises has been used in therapy, but so far, no
      studies have investigated which brain areas are involved in this process.
      Therefore, we performed a study with functional magnetic resonance imaging (fMRI)
      to examine brain areas related to discriminating passively guided shape and
      length discrimination in stroke patients and evaluate whether they differed from
      healthy age-matched controls. Eight subcortical stroke patients discriminated
      different shapes or length based on passive finger movements provided by an fMRI
      compatible robot. The data were contrasted to a control condition whereby
      patients discriminated music fragments. Passively guided somatosensory
      discrimination versus music discrimination elicited activation in similar
      frontoparietal areas in stroke patients compared to the healthy control group.
      Still, patients had increased activation in the right angular gyrus, left
      superior lingual gyrus, and right cerebellar lobule VI compared to healthy
      volunteers. Conversely, healthy volunteers activated the right precentral gyrus
      to a greater extent than patients. In both groups, shape discrimination resulted
      in anterior intraparietal sulcus and premotor activation, while length
      discrimination elicited a more medially located parietal activation with mainly
      right-sided premotor activity. The current study is a first step in clarifying
      brain activations during passively guided shape and length discrimination in
      subcortical stroke patients. Research into the effects of the use of sensory
      discrimination exercises on brain reorganization and brain plasticity is
      encouraged.

PMID- 22648207
TI  - Development of PI3K/AKT/mTOR pathway inhibitors and their application in
      personalized therapy for non-small-cell lung cancer.
AB  - Lung cancer is a common disease with more than 1.6 million new cases diagnosed
      worldwide in 2008. Treatments for patients with advanced disease are rarely
      curative, and responses to therapy are often followed by relapse, which
      highlights the large unmet need for novel therapies. Recent advances in cancer
      treatment have focused on personalized therapy, whereby patients are treated with
      agents that best target the molecular drivers of their disease. Thus, a better
      understanding of the pathways that drive cancer or drug resistance is of critical
      importance. One such example is the phosphatidylinositol 3-kinase
      (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, which is activated in
      many lung cancer patients and represents a target for therapy. PI3K/AKT/mTOR
      pathway activation has also been observed in tumors resistant to agents targeting
      upstream receptor tyrosine kinases. Agents that target this pathway have the
      potential to shut down survival pathways, and are being explored both in the
      setting of pathway-activating mutations and for their ability to restore
      sensitivity to upstream signaling targeted agents. Here, we examine the frequency
      of mutations activating the PI3K/AKT/mTOR pathway, review the novel agents being
      explored to target this pathway, and explore the potential role of the inhibition
      of this pathway in the clinical development of these agents.

PMID- 22648208
TI  - Circulating miR-34a levels are reduced in colorectal cancer.
AB  - INTRODUCTION: MicroRNAs (miRNAs) are small, non-coding RNA segments that regulate
      gene expression via post-transcriptional inhibition and have roles in cell
      differentiation, proliferation, and apoptosis. Expression differs between tumor
      and normal tissue in several malignancies. Most work has focused on tissue and
      cell expression with few reports of circulating miRNAs in colorectal cancer.
      Available biomarkers for colorectal cancer have limited sensitivity and
      specificity, thus there is a need for new markers. AIMS: This study aimed to
      identify miRNAs that are differentially expressed in the blood of colorectal
      cancer patients compared to controls and to establish if this is specific to
      colorectal cancer and thus could be utilized as potential tumor markers. METHODS:
      Blood samples were collected from 63 colorectal cancer patients and 45 controls.
      Expression of 7 target miRNAs (miR-143, miR-145, miR-21, miR-30a-3p, miR-31, miR
      34a, and miR-92) was measured using RQ-PCR. Results were correlated with
      clinicopathological data and analyzed. Analysis of differentially expressed
      circulating miRNAs was expanded to include 62 patients with prostate, renal,
      breast, and melanoma cancers. RESULTS: Analysis of the relative quantification of
      the target miRNAs showed significantly reduced expression (P = 0.004) of miR-34a
      in colorectal cancer. MiR-34a was also significantly reduced in breast cancer (P
      = 0.019). CONCLUSION: This study demonstrates significantly reduced expression of
      circulating miR-34a in colorectal and breast cancer. This may have future
      application as part of a biomarker profile.

PMID- 22648213
TI  - JDD: celebrating 10 years of publishing excellence. Interview with C. William
      Hanke.

PMID- 22648214
TI  - Message from the guest editor.

PMID- 22648215
TI  - Why is rosacea considered to be an inflammatory disorder? The primary role,
      clinical relevance, and therapeutic correlations of abnormal innate immune
      response in rosacea-prone skin.
AB  - The pathophysiology of rosacea has undergone renewed interest over the past
      decade, with a large body of evidence supporting the role of an abnormal innate
      immune response in rosacea. Many mechanisms interact with the cutaneous innate
      immune system that may be operative. A variety of potential triggers stimulate
      this immune detection system which is upregulated and hyper-responsive in facial
      skin of patients with rosacea as compared to normal skin. Based on the most
      current data, two conclusions have been reached. First, the major presentations
      of rosacea appear to be inflammatory dermatoses. Second, the presence of a
      microbial organism is not a primary or mandatory component of the pathogenesis of
      rosacea. Available therapies for rosacea exhibit reported modes of action that
      appear to correlate with the inhibition of inflammatory processes involved in the
      pathophysiology of at least some presentations of rosacea.

PMID- 22648201
TI  - Glycemic index, glycemic load and endometrial cancer risk: results from the
      Australian National Endometrial Cancer study and an updated systematic review and
      meta-analysis.
AB  - PURPOSE: The relationship between habitual consumption of foods with a high
      glycemic index (GI) and/or a diet with a high glycemic load (GL) and risk of
      endometrial cancer is uncertain, and relatively few studies have investigated
      these associations. The objectives of this study were to examine the association
      between GI/GL and risk of endometrial cancer using data from an Australian
      population-based case-control study and systematically review all the available
      evidence to quantify the magnitude of the association using meta-analysis.
      METHODS: The case-control study included 1,290 women aged 18-79 years with newly
      diagnosed, histologically confirmed endometrial cancer and 1,436 population
      controls. Controls were selected to match the expected Australian state of
      residence and age distribution (in 5-year bands) of cases. For the systematic
      review, relevant studies were identified by searching PubMed and Embase databases
      through to July 2011. Random-effects models were used to calculate the summary
      risk estimates, overall and dose-response. RESULTS: In our case-control study, we
      observed a modest positive association between high dietary GI (OR 1.43, 95 % CI
      1.11-1.83) and risk of endometrial cancer, but no association with high dietary
      GL (OR 1.15, 95 % CI 0.90-1.48). For the meta-analysis, we collated information
      from six cohort and two case-control studies, involving a total of 5,569 cases.
      The pooled OR for the highest versus the lowest intake category of GI was 1.15
      (0.95-1.40); however, there was significant heterogeneity (p 0.004) by study
      design (RR 1.00 [95 % CI 0.87-1.14] for cohort studies and 1.56 [95 % CI 1.21
      2.02] for case-control studies). There was no association in the dose-response
      meta-analysis of GI (RR per 5 unit/day increment of GI 1.00, 95 % CI 0.97-1.03).
      GL was positively associated with endometrial cancer. The pooled RR for the
      highest versus the lowest GL intake was 1.21 (95 % CI 1.09-1.33) and 1.06 (95 %
      CI 1.01-1.11) per 50 unit/day increment of GL in the dose-response meta-analysis.
      CONCLUSION: The pooled results from observational studies, including our case
      control results, provide evidence of a modest positive association between high
      GL, but not GI, and endometrial cancer risk.

PMID- 22648216
TI  - Effectiveness and safety of modified-release doxycycline capsules once daily for
      papulopustular rosacea monotherapy results from a large community-based trial in
      subgroups based on gender.
AB  - This article is a prospective planned analysis of data evaluating the
      effectiveness and safety of modified-release doxycycline capsules (30 mg
      immediate-release and 10 mg delayed-release beads) used once daily for up to 12
      weeks in subgroups of males and females with papulopustular (subtype 2) rosacea
      from a large, open-label, multicenter, community-based study. A total of 1421
      patients participated in the study. The per-protocol population comprised 826
      patients on monotherapy, with 28.5% male participants (n=235) and 71.5% female
      participants (n=591). Rosacea was assessed on a 5-point investigator's global
      assessment (IGA) scale (0=clear, 1=near clear, 2=mild, 3=moderate, 4=severe).
      Erythema was also assessed on a 5-point clinician's erythema assessment (CEA)
      scale (0=none, 1=mild, 2=moderate, 3=significant, 4=severe). At baseline, males
      had a higher percentage of IGA scores of 3 (116 per 235; 49.4% versus 273 per
      591; 46.2% in females) and 4 (32 per 235; 13.6% versus 35 per 591; 5.9% in
      females). Significant improvements in severity rating and erythema were observed
      in males and females as demonstrated by shifts in the distribution of IGA and CEA
      scores between baseline and week 12 (P<.001). Treatment success (IGA score of 0
      or 1) at week 12 was achieved in 172 per 235 (73.2%) of males and in 444 per 591
      (75.2%) of females. Adverse events (primarily mild or moderate gastrointestinal
      events) were reported in 9.9% of males and 12.8% of females. Anti-inflammatory
      dose doxycycline, which is administered as a 40 mg modified-release capsule once
      daily was effective and safe as monotherapy for papulopustular rosacea in both
      the female (n=591) and male (n=235) study groups. This specific 40 mg capsule
      delivers 30 mg immediate-release and 10 mg as delayed release using specially
      designed beads, and is subantimicrobial with both single and repeated dosing.

PMID- 22648217
TI  - Post-adolescent acne in women: more common and more clinical considerations.
AB  - Current evidence suggests that post-adolescent acne in women is on the rise. Acne
      in this subgroup of patients commonly follows a specific pattern that can often
      be treatment resistant and/or prone to relapse, including after oral isotretinoin
      therapy. With a plethora of medications to choose from for acne treatment, many
      of which have been used in the past by patients without success, dermatology
      practitioners often find oral contraceptives and spironolactone to be of benefit
      in otherwise healthy adult females. Also, some of these patients may have
      concurrent hormonal anomalies such as polycystic ovarian syndrome or other
      underlying endocrine disorders, which should also be appropriately worked up by
      the clinician and managed accordingly. This article reviews some of the
      underlying pathophysiological factors, available treatment options, and screening
      guidelines to assist clinicians in the management of acne in adult females.

PMID- 22648218
TI  - Effects of benzoyl peroxide 5% clindamycin combination gel versus adapalene 0.1%
      on quality of life in patients with mild to moderate acne vulgaris: a randomized
      single-blind study.
AB  - BACKGROUND: Patients with acne vulgaris often have impaired quality of life
      (QOL). The fixed-dose combination of benzoyl peroxide 5%/clindamycin 1% gel
      (BPO/C) topical gel provides an earlier onset of action and is more effective
      against inflammatory and total facial lesions than adapalene (AP) 0.1% gel.
      OBJECTIVE: To compare BPO/C and AP with regard to the early effect on QOL,
      efficacy, and tolerability in patients with mild to moderate acne vulgaris.
      METHODS: Patients were randomized to BPO/C or AP once nightly for 12 weeks in a
      multicentre, single-blind trial. The primary efficacy endpoint was QOL at week 2,
      assessed using the Skindex-29 questionnaire. Secondary endpoints included grading
      and counting of acne lesions; investigator assessments of peeling, erythema, and
      dryness, and patient-reported burning or itching. Adverse events were monitored
      during the study and during the 14-day minimum follow-up period. RESULTS: A total
      of 168 patients were enrolled, and 114 patients completed the study. In the
      intent-to-treat population, after 2 weeks of treatment, BPO/C was associated with
      a small but noticeably better improvement in global QOL compared with AP (-4.9
      versus -1.1; P<0.001). A greater reduction in both total and inflammatory lesions
      was noted from week 1 onward (P<0.05) with BPO/C versus AP. At all time points,
      BPO/C was better tolerated than AP for all investigator-rated (dryness, peeling,
      erythema) and patient-rated (burning, itching) events (P<0.036). CONCLUSIONS:
      BPO/C is associated with early improvements in QOL compared with AP. These QOL
      improvements are likely to be the result of better efficacy and tolerability
      outcomes observed with BPO/C.

PMID- 22648219
TI  - Diagnosis and treatment of rosacea: state of the art.
AB  - Rosacea is a common disorder that is both under recognized and undertreated.
      Prevalence figures indicate that it may be present in 1 of every 10 adults in a
      primary care waiting room. Untreated, patients with rosacea can suffer
      significant emotional, workplace, and social impairments. While rosacea has been
      recognized since ancient times, only recently have investigators begun to
      identify the pathophysiologic elements responsible for the characteristic
      erythema, flushing, dysesthesias, and papulopustular manifestations of the
      disease. Although the etiology of rosacea is unclear, inflammation appears to be
      a central element. Experimental evidence suggests that abnormalities of the
      skin's innate and adaptive immune responses may play pivotal roles. Once
      recognized, effective topical and systemic therapies can be prescribed to lessen
      the impact of the disease on the patient's life. Although initially administered
      in an empiric fashion, it now seems clear that the role of antibiotics in
      patients with rosacea depends upon their anti-inflammatory rather than their
      antimicrobial properties. Consequently, practitioners have the opportunity to
      practice good antibiotic stewardship when treating the disease, particularly with
      systemic therapies. Therapy with subantimicrobial dosing and with topical
      treatments can modulate the inflammation of rosacea without exerting antibiotic
      pressure responsible for the emergence of antibiotic resistance.

PMID- 22648220
TI  - Relative potency of incobotulinumtoxinA vs onabotulinumtoxinA a meta-analysis of
      key evidence.
AB  - Botulinum neurotoxin-A (BoNT-A) has become widely used in aesthetic applications
      over the past 20 years with several formulations now available. Although widely
      assumed to be equipotent, recent claims that the original commercial formulation,
      onabotulinumtoxinA (Botox(r)/Vistabel(r), Allergan UK, Marlow, UK) is more potent
      than incobotulinumtoxinA (Bocouture(r)/Xeomin(r), Merz Pharma, UK) have raised
      concerns that clinicians may be persuaded to increase doses to the potential
      detriment of their patients. To investigate this further, a review of the
      clinical evidence for the commercially available cosmetic formulations of BoNT-A
      was undertaken alongside a meta-analysis, carried out using mixed treatment
      analysis (MTA) methodology, of the available clinical data in the aesthetic
      setting. This demonstrated that at a dose of 24 units, there was a 94% likelihood
      that incobotulinumtoxinA was more effective than onabotulinumtoxinA in achieving
      a response as defined in the included studies; however, the scale of this
      advantage was not clinically meaningful. Of 11 clinical and preclinical studies
      identified comparing incobotulinumtoxinA and onabotulinumtoxinA directly, the
      weight of evidence suggested that there was no difference in the relative potency
      of the two products. As such, clinicians should continue to consider the
      formulations to be equipotent until such time that compelling clinical evidence
      to the contrary becomes available.

PMID- 22648221
TI  - Safety and efficacy of two anti-acne/anti-aging treatments in subjects with
      photodamaged skin and mild to moderate acne vulgaris.
AB  - BACKGROUND: Although reliable prevalence data are not available, adult acne is
      thought to be somewhat common, and it is not unusual for patients to have acne as
      well as early signs of skin aging. A novel anti-acne/anti-aging formulation
      (Treatment A) has been developed for daily use by patients to address both signs
      of skin aging and facial acne vulgaris. The novel, non-prescription formulation
      includes several ingredients shown to target factors underlying the pathogenesis
      of acne vulgaris while also addressing multiple components in the pathophysiology
      of skin aging. METHODS: A blinded, randomized, split-face study was conducted to
      evaluate and compare the tolerability and efficacy of the novel anti-acne/ anti
      aging product in subjects with photodamaged skin and acne vulgaris relative to
      tretinoin cream 0.025% (Treatment B). All subjects also were given supportive
      skincare, consisting of a cleanser, moisturizer, and sunscreen. Each treatment
      was assessed for its effects on subjects' appearance, lesion count reductions,
      and tolerability. RESULTS: Treatment A produced statistically significantly
      greater improvements in skin tone evenness, skin tone clarity, and blemishes and
      blotchiness. There were also statistically greater reductions in total lesion
      count for acne patients on the side of the face treated with Treatment A compared
      to Treatment B; Treatment A was also associated with early (day 2) improvement in
      skin tone evenness and clarity, tactile skin smoothness, and blemishes and
      blotchiness. Both treatments demonstrated favorable tolerability. CONCLUSION: The
      novel topical anti-aging/anti-acne therapy (Treatment A) within a comprehensive
      skin care regimen of cleanser, moisturizer, and sunscreen may maximize efficacy
      and tolerability and contribute to our armamentarium for treating both
      photodamage and acne at the same time.

PMID- 22648222
TI  - Acne vulgaris: the role of oxidative stress and the potential therapeutic value
      of local and systemic antioxidants.
AB  - Acne vulgaris is a common dermatological condition characterized by hormonally
      mediated sebum overproduction, follicular hyperkeratinization, and chronic
      inflammation of the pilosebaceous unit. Microbes, genetic susceptibilities, and
      various environmental factors have been linked to the pathogenesis of the
      condition. Over the last several years it has become apparent that patients with
      acne are under increased cutaneous and systemic oxidative stress. Moreover, the
      burden of oxidative stress may not be a mere consequence of acne; rather, the
      oxidative stress, lipid peroxidation in particular, may be an early event that
      helps to drive the acne process. Here, we explore the role of oxidative stress
      and review the preliminary research involving the administration of local and
      systemic antioxidants.

PMID- 22648223
TI  - Efficacy and safety of a ceramide containing moisturizer followed by fixed-dose
      clindamycin phosphate 1.2%/benzoyl peroxide 2.5% gel in the morning in
      combination with a ceramide containing moisturizer followed by tretinoin 0.05%
      gel in the evening for the treatment of facial acne vulgaris.
AB  - Combination therapy addressing multiple pathogenic factors should be used to
      achieve optimal outcomes in treating acne. The following study demonstrated both
      safety and efficacy of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide
      2.5% in the morning with micronized tretinoin 0.05% gel in the evening. Both
      products were applied to the skin following the use of a ceramide containing
      moisturizing lotion.

PMID- 22648224
TI  - Trichoscopy of cicatricial alopecia.
AB  - BACKGROUND: Trichoscopy is widely used in differential diagnosis of non
      cicatricial alopecia. OBJECTIVE: The aim of this prospective study was to
      identify possible characteristic trichoscopy patterns of diseases leading to
      primary cicatricial alopecia. METHODS: Trichoscopy was performed in a total of
      1,884 consecutive patients presenting with hair loss. In this group, 84 patients
      were diagnosed with cicatricial alopecia and 1,800 patients with non-cicatricial
      alopecia. Sixty healthy persons served as healthy controls. Trichoscopy was
      performed with the use of Fotofinder II videodermoscopy system. Following unique
      or characteristic features were identified: scattered dark-brown discoloration of
      the skin, large yellow dots and thick arborizing vessels in cutaneous (discoid)
      lupus erythematosus (n=20), tubular perifollicular scaling and elongated blood
      vessels in lichen planopilaris (n=28), minor perifollicular scaling in frontal
      fibrosing alopecia (n=19), tufted hairs with starburst pattern perifollicular
      hyperplasia in folliculitis decalvans (n=9) and large, "3D" yellow dots imposed
      over dystrophic hairs in dissecting cellulitis (n=8). RESULTS: All patients with
      cicatricial alopecia trichoscopy showed white and milky-red areas lacking
      follicular openings. These features were not found in patients with non
      cicatricial alopecia or healthy controls. CONCLUSION: These results indicate that
      trichoscopy may be applied as a quick and non-invasive auxiliary method in
      differential diagnosis of diverse diseases leading to cicatricial alopecia, such
      as cutaneous lupus erythematosus, classic lichen planopilaris, frontal fibrosing
      alopecia, folliculitis decalvans, and dissecting cellulitis.

PMID- 22648225
TI  - Complex forehead defects: a novel reconstructive technique and review of
      available methods.
AB  - Complex forehead defects may result from excision of tumors or trauma. The
      reconstructive challenge is determined by the extent of tissue loss, the quality
      of the remaining tissue, possibly comprised vascular supply to the affected
      region, and special considerations (eg, exposed bone or injury to underlying
      structures). This paper describes a novel reconstructive approach to correct a
      complex forehead defect with exposed bone and discusses the armamentarium of
      reconstructive options for such cases.

PMID- 22648227
TI  - Livedo reticularis associated with rasagiline (azilect).
AB  - This is a case report of a 69-year-old female with Parkinson's disease who
      developed an asymptomatic eruption on her legs bilaterally. Clinical and
      histologic examination was consistent with livedo reticularis, which was
      temporally associated with initiation of rasagiline. The pathogenesis of livedo
      reticularis is discussed along with the possible mechanisms for both rasagiline
      and amantidine causing drug-induced livedo reticularis in patients.

PMID- 22648229
TI  - Capecitabine-induced systemic lupus erythematosus and palmoplantar
      erythrodysesthesia.
AB  - Capecitabine is emerging as an important drug in the treatment of metastatic
      breast and colorectal cancers. Marketed as Xeloda (r), this prodrug is taken
      orally and readily absorbed. It is novel in its increased convenience for
      patients, similar efficacy to the intravenous form of its active metabolite and
      its increased tolerability.1 We present a woman with metastatic breast cancer who
      presented with cutaneous abnormalities two months after starting treatment with
      capecitabine. Various dermatologic side effects have been attributed to
      capecitabine, often requiring cessation of the offending drug. We describe an
      unreported dermatological side effect of capecitabine therapy, systemic lupus
      erythematosus concurrent with palmoplantar erythrodysesthesia. As the use of this
      chemotherapeutic agent becomes more prevalent, it is important to recognize the
      range of its cutaneous side effects.

PMID- 22648230
TI  - Resident rounds: Part III generalized linear porokeratosis.

PMID- 22648231
TI  - Herbal medicine in dermatology: does natural = safe?

PMID- 22648236
TI  - How should primary care doctors select which antidepressants to administer?
AB  - Clinicians can choose among various second-generation antidepressants for
      treating depressive disorders, such as major depressive disorder, subsyndromal
      depression, or dysthymia. Systematic reviews indicate that available drugs differ
      in frequency of administration, costs, and the risks of some adverse events but
      have similar efficacy for treating major depressive disorder. Furthermore,
      evidence does not support the choice of one antidepressant over another based on
      accompanying symptoms, such anxiety, insomnia, or pain. Available studies provide
      little guidance for clinicians about the benefits of second-generation
      antidepressants for treating dysthymia and subsyndromal depression. Evidence is
      also unclear about the comparative risks of serious adverse events, such as
      suicidality, seizures, fractures, increased bleeding, or serotonin syndrome. This
      article summarizes the best available evidence regarding comparative benefits and
      harms of second-generation antidepressants for treating depressive disorders.

PMID- 22648237
TI  - Non-tortuous ionic transport in robust micellar liquid crystalline phases with
      cubic symmetry.
AB  - A micellar cubic LC phase consisting of a hydrophilic matrix exhibited enhanced
      ionic transport and mechanical properties without macroscopic orientation, which
      are attributed to the non-tortuous ionic transport and highly symmetric cubic
      lattice, respectively.

PMID- 22648235
TI  - Cell delivery routes for stem cell therapy to the heart: current and future
      approaches.
AB  - An important factor to determine the success of stem cell therapy to the heart is
      the choice of cell delivery route. This will affect the fate of donor cells and
      subsequently influence the outcome of treatment; however, there is currently no
      optimum cell delivery route appropriate for every disease condition or every
      donor cell type. This review summarises currently available approaches for
      administering cells to the heart, with a particular focus on cell
      retention/survival and the therapeutic benefits seen in preclinical and clinical
      studies. Two major approaches are intracoronary and intramyocardial injection,
      which have been widely used for the delivery of various types of cells. Although
      there are advantages to both approaches, donor cell retention and survival are
      poor using these methods, potentially limiting therapeutic effects. Various
      attempts to improve current approaches, along with the development of emerging
      new approaches, are also described and discussed in this review.

PMID- 22648238
TI  - Evaluation of a technique for in vivo internal monitoring of (18)F within a
      Brazilian laboratory network.
AB  - (18)FDG, an analogue of glucose labelled with the radionuclide (18)F, is the most
      widely used radiopharmaceutical in positron emission tomography/computed
      tomography technique. In Brazil, there are currently eight (18)FDG plants in
      operation and other facilities are expected to start their production in the near
      future. The growth in the production and clinical use of (18)FDG represents an
      increasing risk of worker exposures. According to national regulations and
      international recommendations, internal exposures should be effectively
      controlled in order to keep doses as low as possible. The implementation of a
      routine monitoring programme towards the estimation of internal doses related to
      the incorporation of (18)F is difficult, mainly due to its short physical half
      life, the cost of a bioassay laboratory and the need of a monitoring service
      promptly available near the production plant. This paper describes the
      implementation and evaluation of a methodology for in vivo brain monitoring of
      (18)F to be applied in cases of suspected incorporation of (18)FDG. The technique
      presented a minimum detectable effective dose in the order of nanoSieverts, which
      allows its application for occupational monitoring purposes.

PMID- 22648239
TI  - Preparation of Ca-alginate biopolymer beads and investigation of their
      decorporation characteristics for 85Sr, 238U and 234Th by in vitro experiments.
AB  - The aim of this work was to investigate whether Ca-alginate biopolymer beads
      (CaABBs) can be used to reduce the bioavailability of radionuclides in the
      gastrointestinal tract of humans. The uptake of strontium, uranium and thorium
      from a simulated gastrointestinal system was studied by in vitro techniques using
      CaABBs. This agent was prepared from Na-alginate through cross-linking with
      divalent calcium ions according to the egg-box model. The effects of process
      variables such as pH of the gastrointestinal juice, incubation time and solid-to
      solution ratio for the removal of radionuclides from the gastrointestinal juice
      were investigated. The results suggest that CaABBs are a potent material for
      reducing the bioavailability of radionuclides with a high uptake efficiency in
      the gastrointestinal tract.

PMID- 22648240
TI  - Induction of osteoporosis with its influence on osteoporotic determinants and
      their interrelationships in rats by DEXA.
AB  - BACKGROUND: As women are the population most affected by multifactorial
      osteoporosis, research is focused on unraveling the underlying mechanism of
      osteoporosis induction in rats by combining ovariectomy (OVX) either with
      calcium, phosphorus, vitamin C and vitamin D2/D3 deficiency, or by administration
      of glucocorticoid (dexamethasone). MATERIAL/METHODS: Different skeletal sites of
      sham, OVX-Diet and OVX-Steroid rats were analyzed by Dual Energy X-ray
      Absorptiometry (DEXA) at varied time points of 0, 4 and 12 weeks to determine and
      compare the osteoporotic factors such as bone mineral density (BMD), bone mineral
      content (BMC), area, body weight and percent fat among different groups and time
      points. Comparative analysis and interrelationships among osteoporotic
      determinants by regression analysis were also determined. RESULTS: T scores were
      below-2.5 in OVX-Diet rats at 4 and 12 weeks post-OVX. OVX-diet rats revealed
      pronounced osteoporotic status with reduced BMD and BMC than the steroid
      counterparts, with the spine and pelvis as the most affected skeletal sites.
      Increase in percent fat was observed irrespective of the osteoporosis inducers
      applied. Comparative analysis and interrelationships between osteoporotic
      determinants that are rarely studied in animals indicate the necessity to analyze
      BMC and area along with BMD in obtaining meaningful information leading to proper
      prediction of probability of osteoporotic fractures. CONCLUSIONS: Enhanced
      osteoporotic effect observed in OVX-Diet rats indicates that estrogen
      dysregulation combined with diet treatment induces and enhances osteoporosis with
      time when compared to the steroid group. Comparative and regression analysis
      indicates the need to determine BMC along with BMD and area in osteoporotic
      determination.

PMID- 22648242
TI  - Bony wall damage in the region of the middle and posterior cranial fossa observed
      during otosurgery.
AB  - BACKGROUND: Bony wall damages in the region of the middle and posterior cranial
      fossa are usually observed in cases of chronic otitis media. These defects can
      also be congenital, post-traumatic, iatrogenic or due to tumors. They can
      potentially lead to the development of intracranial complications.
      MATERIAL/METHODS: We analyzed patients who were diagnosed as having bony wall
      damage in the region of the middle and/or posterior cranial fossa. We also
      discuss methods of reconstruction during otosurgery. The analysis involves
      patients who underwent middle ear operations in the Department of Otolaryngology
      at the Jagiellonian University of Krakow between 2004 and 2008; 495 otosurgeries
      were performed during this period of time. RESULTS: In 70% of patients the reason
      for otosurgery was chronic otitis media. In 20%, bone defects occurred
      simultaneously with otosclerosis. Less than 10% underwent otosurgery for other
      reasons. Bony wall damage in the region of the middle and posterior cranial fossa
      were diagnosed in 46 patients who underwent surgery. In patients with bony wall
      damage, otogenic intracranial complications were described in 14 cases.
      CONCLUSIONS: The performed reconstruction methods for bony wall damage, which
      used the fascia, strengthened with the pedicle muscle flap for larger defects and
      with either bone lamella or cartilage in specific cases, proved successful.
      Nearly 80% of bony wall damages in the region of the middle and posterior cranial
      fossa remain asymptomatic and are discovered incidentally during middle ear
      surgery. The above observations emphasize the significant role of pre-operative
      imaging diagnostics.

PMID- 22648241
TI  - Acrylonitrile-induced gastric toxicity in rats: the role of xanthine oxidase.
AB  - BACKGROUND: Acrylonitrile (ACN) is an extensively produced aliphatic nitrile. The
      gastrointestinal tract is an important target organ for ACN toxicity. The
      objective of the present study was to investigate the role of xanthine oxidase
      (XO) in ACN-induced gastric toxicity in rats. MATERIAL/METHODS: We assessed the
      effect of ACN on oxidative stress parameters as xanthine oxidase (XO) and total
      xanthine dehydrogenase (XD)/ XO activity, superoxide anion (O(2)(.-)) production,
      reduced glutathione (GSH) levels and lipid peroxidation in gastric tissues.
      RESULTS: A single oral dose of ACN (25 mg/kg) caused a significant enhancement in
      XO activity. ACN also caused a significant depletion of GSH levels, enhanced
      O(2)(.-) production and increased lipid peroxidation in the time-course
      experiment. In the dose-response experiment, ACN accelerated the conversion of XD
      to XO, with a significant depletion of gastric GSH in a dose-related manner. A
      strong negative correlation existed between the levels of GSH and the percentage
      enhancement in XO activity (r =-0.997). (O(2)(.-)) production and malondialdehyde
      (MDA) formation were significantly elevated in a dose-related manner.
      Pretreatment with allopurinol (50 mg/kg) significantly protected against ACN
      induced rise in XO activity, depletion of GSH, and elevated production of (O(2)(.
      )). However, pretreatment with diethyl maleate (DEM; 100 mg/kg) significantly
      aggravated the ACN-induced GSH depletion and rise in XO activity. Furthermore,
      DEM significantly enhanced (O(2)(.-)) and MDA production. CONCLUSIONS: The
      present study indicates that enhancement of XO activity could be implicated in
      ACN-induced gastric damage in rats.

PMID- 22648243
TI  - Improved real-time PCR assay for detection and quantification of all 54 known
      types of human adenoviruses in clinical samples.
AB  - BACKGROUND: Detection and quantification of adenoviruses (AdVs) causing life
      threatening complications are important abilities in recognition of infection and
      management of immunocompromised patients. Due to the rapid increase in the number
      of known AdV types, most commercial tests for detection and identification of
      AdVs are outdated. MATERIAL/METHODS: We designed an improved, easier and faster
      real-time quantitative polymerase chain reaction (RQ-PCR) method for detection
      and quantification of 54 types of human AdVs. A wide validation effort was
      undertaken to ensure confidence in highly sensitive and specific detection of
      AdVs in compromised patients. The validation process included evaluation of the
      method's suitability and reliability for use in routine diagnostics. RESULTS: Due
      to high sensitivity (9.2*102 copies/ml) and broad dynamic range (7 log) we are
      able to detect specific viral DNA in large amounts of cell-free body fluids. The
      new assay is characterized by high precision and low variation within and between
      individual virus tests (CV=0.036%, CV=1.29%), low bias error (4%) and no cross
      reactivity with other pathogens. CONCLUSIONS: The implementation of this new
      assay in clinical and laboratory practice provides a rapid, reliable and less
      laborious method for detection and monitoring of AdV replication in
      immunocompromised patients. Moreover, it offers the ability to distinguish
      between active and latent infection and assess treatment efficiency.

PMID- 22648244
TI  - Osthole, a herbal compound, alleviates nucleus pulposus-evoked nociceptive
      responses through the suppression of overexpression of acid-sensing ion channel 3
      (ASIC3) in rat dorsal root ganglion.
AB  - BACKGROUND: Osthole (Ost), a natural coumarin derivative, has been shown to
      inhibit many pro-inflammatory mediators and block voltage-gated Na+ channels.
      During inflammation, acidosis is an important pain inducer which activates
      nociceptors by gating depolarizing cationic channels, such as acid-sensing ion
      channel 3 (ASIC3). The aim of this study was to examine the effects of Ost on
      nucleus pulposus-evoked nociceptive responses and ASIC3 over-expression in the
      rat dorsal root ganglion, and to investigate the possible mechanism.
      MATERIAL/METHODS: Radicular pain was generated with application of nucleus
      pulposus (NP) to nerve root. Mechanical allodynia was evaluated using von Frey
      filaments with logarithmically incremental rigidity to calculate the 50%
      probability thresholds for mechanical paw withdrawal. ASIC3 protein expression in
      dorsal root ganglions (DRGs) was assessed with Western blot and
      immunohistochemistry. Membrane potential (MP) shift of DRG neurons induced by
      ASIC3-sensitive acid (pH6.5) was determined by DiBAC(4) (3) fluorescence
      intensity (F.I.). RESULTS: The NP-evoked mechanical hyperalgesia model showed
      allodynia for 3 weeks, and ASIC3 expression was up-regulated in DRG neurons,
      reaching peak on Day 7. Epidural administration of Ost induced a remarkable and
      prolonged antinociceptive effect, accompanied by an inhibition of over-expressed
      ASIC3 protein and of abnormal shift of MP. Amiloride (Ami), an antagonist of
      ASIC3, strengthened the antinociceptive effect of Ost. CONCLUSIONS: Up-regulation
      of ASIC3 expression may be associated with NP-evoked mechanical hyperalgesia. A
      single epidural injection of Ost decreased ASIC3 expression in DGR neurons and
      the pain in the NP-evoked mechanical hyperalgesia model. Osthole may be of great
      benefit for preventing chronic pain status often seen in lumbar disc herniation
      (LDH).

PMID- 22648245
TI  - Polo-like kinase 1 is overexpressed in colorectal cancer and participates in the
      migration and invasion of colorectal cancer cells.
AB  - BACKGROUND: Polo-like kinase 1 (PLK1) is an important molecule in proliferation
      of many human cancers. The aim of study is to clarify the expression patterns and
      potential function of PLK1 in colorectal cancers. MATERIAL/METHODS: Fifty-six
      colorectal cancers samples were collected and arranged onto a tissue array and
      the expression of PLK1 were detected by immunohistochemistry and correlated with
      clinico-pathological characteristics and expression of PCNA. Expression of PLK1
      in 9 colorectal cancer cells lines was investigated by RT-PCR and Western blot,
      then SW1116 cells lines were treated with PLK1 siRNA and the efficiency was
      examined by Western blot. Transwell test was applied to detect the migration and
      invasion capability of cancer cells by counting the number of cells passing
      through the membranes. Cell proliferation and apoptosis were examined by Cell
      Counting Kit-8 (CCK-8) and Annexin-V Kit. RESULTS: PLK1 was positively expressed
      in 73.2% (41/56) of colorectal cancers tissues, but in only 3.6% (2/56) of normal
      tissues, and was associated with Duke's stage (P<0.01), tumor size (P<0.01),
      invasion extent (P<0.05) and lymphatic metastasis (P<0.01). The expression of
      PLK1 was correlated with expression of PCNA (R=0.553, P<0.01). PLK1 was inhibited
      in SW1116 cells by treating with PLK1 siRNA oligos, which resulted in a decreased
      number of cells passing through the membrane as compared with control groups
      (P<0.01) at 24 hours after transfection. Cell proliferation was inhibited from 48
      hours after transfection, while cells apoptosis was induced from 72 hours after
      transfection. CONCLUSIONS: PLK1 could be a progression marker for colorectal
      cancer patients and PLK1 depletion can inhibit migration and invasion capability
      of colorectal cancer cells SW1116, suggesting that PLK1 might be involved in
      metastasis and invasion of colorectal cancer. Therapeutic strategies targeting
      PLK1 may be a new approach to colorectal cancer.

PMID- 22648246
TI  - Selective COX-2 inhibitor ameliorates osteoarthritis by repressing apoptosis of
      chondrocyte.
AB  - BACKGROUND: Celecoxib has a positive effect on human osteoarthritic cartilage,
      but the mechanisms remain unclear. The aim of this study was to test whether
      celecoxib could inhibit the apoptosis of chondrocyte and ameliorate type II
      collagen synthesis to relieve symptoms of OA (osteoarthritis). MATERIAL/METHODS:
      130 Wistar rats were randomly divided into 4 groups as celecoxib (CE), ibuprofen
      (IBP), indomethacin (IN) and normal saline group (NS). The osteoarthritis was
      induced by the excision of the left Achilles tendon. At the 3th, 6th, 9th month
      of treatment, the histological structure of articular cartilage was observed
      using HE staining. Type II collagen was examined using immunohistochemistry.
      Chondrocyte apoptosis was detected by TUNEL staining, and the change of ultra
      microstructure of chondrocyte was examined through a transmission electron
      microscope. RESULTS: CE reduced the OA-like histological changes and suppressed
      chondrocyte apoptosis. However, IN or IBP had deleterious effects on articular
      cartilage and enhanced the chondrocyte apoptosis. IBP promoted the expression of
      type II collagen, and IN inhibited its expression, but had no effect in the CE
      group. CONCLUSIONS: CE had favorable action on OA progression, and may be the
      ideal choice in the treatment of chronic destructive joint disease where anti
      inflammatory drugs need to be used for a prolonged period.

PMID- 22648247
TI  - Therapeutic challenges and management of heart failure during pregnancy (part 2).
AB  - A particularly dangerous condition in pregnant women is already dilated left
      ventricle with severe functional impairment. Taking as an example the case of
      woman with dilated cardiomyopathy (DCM) first diagnosed in 17th week of
      pregnancy, the paper discusses diagnostic, therapeutic challenges and management
      of heart failure during pregnancy. Repeat measurements of brain natiuretic
      peptide levels should be helpful in diagnosing heart failure. To distinguish DCM
      from peripartum cardiomyopathy the time of manifestation should be considered.
      The risk of serious events is associated with NYHA class and impairment of left
      ventricular ejection fraction. Angiotensin-converting enzyme inhibitors (ACE-I)
      and angiotensin-II receptor blockers are contraindicated in pregnancy because of
      fetal toxicity. The incidence of sight effects is associated with time of
      administration of ACE-I and duration of treatment. Possible sight effects of
      drugs in fetus should be monitored (mainly ultrasonographically). ICD can be
      implanted during pregnancy if indicated. To assess the time and mode of delivery,
      a multidisciplinary team of different specialists is required. Subsequent
      pregnancy is contraindicated in a patient with DCM and low ejection fraction of
      left ventricle.

PMID- 22648248
TI  - Differences in endothelial function between Korean-Asians and Caucasians.
AB  - BACKGROUND: The vascular endothelium plays an integral role in maintaining
      vascular homeostasis, including the regulation of blood flow, vascular tone, and
      platelet aggregation. The aim of this study was to see if there were any
      differences in endothelial function between Koreans and Caucasians.
      MATERIAL/METHODS: This was accomplished by 2 measures of endothelial function-
      the response to local heat and the response to vascular occlusion. Ten Caucasian
      and 10 Korean male and female subjects participated (<35 years old). Endothelial
      function was assessed by the skin blood flow response to local heat using a
      thermode for 6 minutes at 3 temperatures (38 degrees C, 40 degrees C and 42
      degrees C) and by vascular occlusion for 4 minutes followed by release and
      measurement of skin blood flow for 2 minutes. RESULTS: When applying 6 minutes of
      local heat at 3 different temperatures (38 degrees C, 40 degrees C, and 42
      degrees C), the skin blood flows were significantly higher for all temperatures
      in Caucasians as compared with Koreans, with peak blood flow of 223+/-48.1,
      413.7+/-132.1, and 517.4+/-135.8 flux in Caucasians and 126.4+/-41.3, 251+/-77.9,
      and 398+/-97.2 flux in Koreans, respectively (p=0.001). Results of this study
      support the idea that the skin blood flow response to occlusion was significantly
      higher in Caucasians (peak 411.9+/-88.9 flux) than Koreans (peak 332.4+/-75.8
      flux) (p=0.016). CONCLUSIONS: These findings suggest that Koreans may have lower
      endothelial function than Caucasians, which may be explained, in part, by genetic
      variations between the 2 ethnic groups.

PMID- 22648249
TI  - Novel GATA4 mutations in patients with congenital ventricular septal defects.
AB  - BACKGROUND: Ventricular septal defect (VSD) is the most prevalent type of
      congenital heart disease and is a major cause of substantial morbidity and
      mortality in infants. Accumulating evidence implicates genetic defects,
      especially in cardiac transcription factors, in the pathogenesis of VSD. However,
      VSD is genetically heterogeneous and the genetic determinants for VSD in most
      patients remain to be identified. MATERIAL/METHODS: A cohort of 230 unrelated
      patients with congenital VSD was included in the investigation. A total of 200
      unrelated ethnically matched healthy individuals were recruited as controls. The
      entire coding region of GATA4, a gene encoding a zinc-finger transcription factor
      essential for normal cardiac morphogenesis, was sequenced initially in 230
      unrelated VSD patients. The available relatives of the mutation carriers and 200
      control subjects were subsequently genotyped for the presence of identified
      mutations. RESULTS: Four heterozygous missense GATA4 mutations of p.Q55R, p.G96R,
      p.N197S, and p.K404R were identified in 4 unrelated patients with VSD. These
      mutations were not detected in 200 control individuals nor described in the human
      SNP database. Genetic analysis of the relatives of the mutation carriers showed
      that in each family the mutation co-segregated with VSD. CONCLUSIONS: These
      findings expand the mutation spectrum of GATA4 linked to VSD and provide new
      insight into the molecular etiology responsible for VSD, suggesting potential
      implications for the genetic diagnosis and gene-specific therapy for VSD.

PMID- 22648250
TI  - Hemorheological responses to progressive resistance exercise training in healthy
      young males.
AB  - BACKGROUND: This study aimed to explore the effects of progressive resistance
      exercise training (PRET) on hemorheology. MATERIAL/METHODS: Exercise sessions
      included 1-3 sets of 8-12 repetitions at 40-60% of 1-repetition maximum (1-RM)
      for 3 weeks and at 75-80% of 1-RM during weeks 4-12. Red blood cell (RBC)
      deformability and aggregation were determined by ektacytometry, plasma and whole
      blood viscosities (WBV) by rotational viscometry. Lactate concentration was
      evaluated by an analyzer and fibrinogen was evaluated by coagulometry. Plasma
      total oxidant/antioxidant status was measured by colorimetry. RESULTS: Following
      an acute increase after exercise on the first day, RBC deformability was elevated
      during weeks 3 and 4 (p=0.028; p=0.034, respectively). The last exercise protocol
      applied in week 12 again caused an acute increase in this parameter (p=0.034).
      RBC aggregation was increased acutely on the first day, but decreased after that
      throughout the protocol (p<0.05). At weeks 4 and 12 pre-exercise measurements of
      WBV at standard hematocrit and plasma viscosity were decreased (p=0.05; p=0.041,
      respectively), while post-exercise values were increased (p=0.005; p=0.04,
      respectively). Post-exercise WBV at autologous hematocrit measured at week 12 was
      increased (p=0.01). Lactate was elevated after each exercise session (p<0.05).
      Fibrinogen was decreased on the third week (p<0.01), while it was increased on
      the 4th week (p=0.005). Plasma antioxidant status was increased at week 3
      (p=0.034) and oxidative stress index was decreased at week 4 (p=0.013) after
      exercise. CONCLUSIONS: The results of this study indicate that PRET may have
      positive effects on hemorheological parameters.

PMID- 22648251
TI  - Increased expression of importin13 in endometriosis and endometrial carcinoma.
AB  - BACKGROUND: Importin13 (IPO13) is a novel potential marker of corneal epithelial
      progenitor cells. We investigated the expression and localization of IPO13 in
      endometrial, endometriotic and endometrial carcinoma tissue. MATERIAL/METHODS:
      IPO13 expression in endometrial, endometriotic and endometrial carcinoma tissue
      was examined by immunohistochemistry, qPCR and Western blot. RESULTS:
      Immunohistochemistry studies showed that IPO13 protein was expressed mainly in
      cytoplasm of glandular epithelial cell and stromal cells. The rate of importin13
      positive cells in proliferative phase endometrium was higher (by about 6-fold)
      than that in secretory endometrium (P<0.05) and the rate of importin13-positive
      cells in endometriosis and endometrial carcinoma was higher than that in normal
      secretory phase endometrial tissues (by about 4- and 9-fold, respectively).
      Immunofluorescence microscopy revealed co-localization of IPO13 with CD34, CD45,
      c-kit, telomerase, CD90 and CD146. QPCR revealed significantly increased IPO13
      mRNA in endometriosis and endometrial carcinoma versus secretory phase
      endometrium (by about 2- and 10-fold, respectively). Western blot analysis showed
      that IPO13 protein is enhanced in endometriosis and endometrial carcinoma versus
      secretory phase endometrium (p<0.05). CONCLUSIONS: These results demonstrate an
      increased expression of IPO13 in endometriosis and endometrial carcinoma, which
      could be involved in the pathogenesis of endometriosis and endometrial carcinoma;
      IPO13 can serve as an endometrial progenitor/stem cell marker.

PMID- 22648252
TI  - Social intelligence and adequate self-expression in patients with orbitofrontal
      cortex injury and in the criminals.
AB  - BACKGROUND: The aim of present article is to compare patients with damage to the
      orbitofrontal cortex and prison inmates in terms of social intelligence and
      social intelligence monitoring. In addition, personal principles and emotional
      regulation of behavior will be assessed in both groups. MATERIAL/METHODS: 20
      patients with orbitofrontal cortical injury, 20 prisoners and 20 controls
      answered questions from the Social Interactions Assessment Questionnaire. Then
      they evaluated their self-disclosure, reported their emotions related to self
      disclosure and declared their personal principles concerning conversations with
      strangers. RESULTS: The patients with damage to the orbitofrontal cortex
      disclosed themselves to a stranger less appropriately than did other subjects,
      and did not assess it critically. They also violated their own declared
      principles, but did not feel embarrassed because of that. The prison inmates
      spoke out less forthrightly on many topics and felt confused during the whole
      examination. CONCLUSIONS: Damage to the the orbital part of frontal lobes may
      result in a disorder of self-disclosure monitoring and impairment of social
      intelligence in conversations with unknown persons. Prison inmates give
      information about themselves unwillingly, which may result from their specific
      experiences during criminal and judicatory procedures and confinement.

PMID- 22648253
TI  - A prospective study on different methods for the treatment of choroidal
      neovascularization. The efficacy of verteporfin photodynamic therapy,
      intravitreal bevacizumab and transpupillary thermotherapy in patients with
      neovascular age-related macular degeneration.
AB  - BACKGROUND: The aim of this study was to compare the efficacy of verteporfin
      photodynamic therapy (PDT), intravitreal injections of bevacizumab (IVB) and
      transpupillary thermotherapy (TTT) in patients with neovascular age-related
      macular degeneration (AMD). MATERIAL/METHODS: The study design was a prospective,
      interventional, comparative case series. Between December 2006 and March 2009,
      426 eyes of 426 consecutive patients presenting with neovascular AMD were
      included into the study. Patients presented with subfoveal CNV predominantly
      classic, minimally classic, and occult with no classic component; lesion size
      less than 5000 um in the greatest linear dimension, and the area of hemorrhages
      <=1/3 were randomized to receive either PDT (group I) or IVB (group II) in a 1:1
      ratio. Other patients with CNV were included into the group III and received TTT.
      RESULTS: One hundred eyes were treated with PDT. Mean baseline logMAR BCVA was
      0.62 and final visual acuity decreased to 0.74 (p<0.05, Wilcoxon test); 104 eyes
      were treated with IVB. Mean baseline BCVA was 0.82 and final visual acuity
      increased to 0.79 (p>0.05, Wilcoxon test); 222 patients were treated with TTT.
      Mean baseline BCVA was 1.10 and final visual acuity decreased to 1.15 (p>0.05,
      Wilcoxon test). Among all eyes the average number of treatment sessions was 2.34
      (SD 1.17). CONCLUSIONS: Our study shows that IVB injections had the best efficacy
      in the improvement of final BCVA. However, both IVB and TTT demonstrated good
      stabilization of vision. Although after PDT final BCVA was significantly worse
      from baseline, it may also be beneficial for some patients with neovascular age
      related macular degeneration.

PMID- 22648254
TI  - Genetic variations in E-selectin and ICAM-1: relation to atherosclerosis.
AB  - BACKGROUND: This study aimed to investigate the association of both intercellular
      adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule (E-selectin)
      polymorphisms using PCR technique and their role in the pathogenesis of
      atherosclerosis. MATERIAL/METHODS: The study enrolled 285 individuals, classified
      into 4 groups: 63 cerebrovascular atherosclerotic patients, 75 cardiovascular
      patients, 72 peripheral atherosclerotic patients and 75 normal healthy
      individuals. RESULTS: The frequency of the mutant AC genotype of E-selectin in
      peripheral, cerebral and cardiovascular atherosclerotic patients was
      significantly higher than in control subjects (29.17%, 28.53% and 28% vs. 8%,
      respectively). However, no significant difference was observed in the frequency
      of mutant CC allele between all atherosclerotic patients and control groups. The
      frequency of the mutant EE homozygotes of ICAM-1 in peripheral, cerebral and
      cardiovascular atherosclerotic patients was significantly higher compared to
      controls (45.8%, 42.9% and 36% vs. 12%, respectively). The frequency of EK of
      ICAM-1 showed no significant difference between atherosclerotic patients and the
      control group. The frequency of the mutant E allele of ICAM-1 was significantly
      higher in peripheral, cerebral and cardiovascular patients compared to controls
      (58.3%, 54.8% and 54% vs. 26%, respectively). CONCLUSIONS: Ser 128Arg of E
      selectin and the K469E of ICAM-1 polymorphisms may be involved in predisposition
      to atherosclerosis.

PMID- 22648255
TI  - Clinical and cognitive correlates of the proton magnetic resonance spectroscopy
      measures in chronic schizophrenia.
AB  - BACKGROUND: Proton magnetic resonance spectroscopy (1H MRS) allows for examining
      brain functions in vivo in schizophrenic patients. Correlations between N
      acetylaspartate (NAA) level in the frontal lobe and cognitive functions and
      clinical symptoms have been observed. The aim of the present study was evaluation
      of relationship between clinical symptoms, cognitive outcomes and brain function
      in 1H MRS measures in schizophrenic patients. MATERIAL/METHODS: The study
      included a group of 47 patients with chronic schizophrenia. Patients were
      assessed by means of PANSS, CGI, and a battery of cognitive tests: WCST, TMT, and
      verbal fluency test. MRI and MRS procedures were performed. Regions of interest
      were located in the left frontal lobe, temporal lobe and thalamus. Metabolite
      (NAA, choline, myoinositol and Glx complex) ratios to creatine were calculated.
      RESULTS: We observed a significant negative correlation between myoinositol level
      in the frontal lobe and WSCT test performance. These data were confirmed by
      further analysis, which showed a significant correlation between WCST outcome,
      negative symptoms score, education level and myoinositol ratio in the frontal
      lobe. When analyzing negative symptoms as independent variables, the analysis of
      regression revealed a significant relationship between negative symptoms score
      and verbal fluency score, together with choline level in the thalamus.
      CONCLUSIONS: The above data seem to confirm a significant role of the thalamus--a
      "transmission station" involved in connections with the prefrontal cortex--for
      psychopathology development (especially negative) in schizophrenia. Moreover, our
      results suggest that a neurodegenerative process may be involved in schizophrenia
      pathogenesis.

PMID- 22648256
TI  - Polyacrylamide hydrogel injection for breast augmentation: another injectable
      failure.
AB  - BACKGROUND: Increasing complications of polyacrylamide hydrogel (PAAG)
      augmentation mammoplasty, such as chronic persistent infection, have recently
      caught the attention of both the medical field and the general public.
      MATERIAL/METHODS: A total of 96 patients with severe chronic infection following
      PAAG augmentation mammoplasty were treated in the present study including 63
      cases with infection confined to the breast and 33 with systemic infection.
      Endoscopy and surgery were performed to completely remove the materials and clear
      the infected tissues followed by drug-irrigation and vacuum-assisted closure for
      several days. RESULTS: In patients with severe infection there were large amounts
      of PAAG, fibers and infiltration of numerous neutrophils and macrophages. The
      infection-inducing materials were extensively dispersed in the mammary and
      subcutaneous tissues, pectoral fascia and intermuscular space. In addition, there
      was scattered distribution of PAAG materials in the armpit, chest wall and
      abdominal wall, which were mixed with necrotic tissues and surrounded by
      lymphocytes, giant cells, macrophages and other inflammatory cells, forming
      chronic granulomatous and fibrous lesions. Infection was controlled following
      surgical intervention. No residual infectious foci or recurrent infections were
      noted among these patients. Although the severe infection did not result in
      mastectomy, patients had breast atrophy and various degrees of deformation.
      CONCLUSIONS: Chronic infection following PAAG augmentation mammaplasty usually
      causes systemic infection and other devastating adverse reactions. This study
      confirms PAAG augmentation mammaplasty is another failed attempt. More attention
      should be paid to the injection of large doses of liquid filler.

PMID- 22648257
TI  - Irreversible electroporation of lung neoplasm: a case series.
AB  - BACKGROUND: Percutaneous irreversible electroporation (IRE) of lung tumors is a
      new minimally invasive technique which has recently been used in the treatment of
      soft tissue tumors. CASE REPORTS: The case histories are presented of two
      patients with unresectable malignancies in the lung, who underwent irreversible
      electroporation as a treatment attempt. The procedure was performed under CT
      guidance and was uneventful. CONCLUSIONS: At follow up 6 months later, the tumors
      both appeared to have recurred. To our knowledge, no similar cases have
      previously been reported in the literature.

PMID- 22648258
TI  - Primary epiploic appendagitis and successful outpatient management.
AB  - BACKGROUND: Primary epiploic appendagitis (PEA) is a rare cause of abdominal
      acute or subacute complaints. Diagnosis of PEA is made with ultrasonography (US)
      or when computed tomography (CT) reveals a characteristic lesion. CASE REPORT: We
      report on two patients with PEA. In one patient PEA was first seen with US and
      confirmed with contrast enhanced CT, and in the second patient CT without
      contrast enhancement demonstrated PEA. In both patients an outpatient recovery
      with conservative non-surgical treatment is described. CONCLUSIONS: Medical
      personnel should be aware of this rare disease, which mimics many other intra
      abdominal acute and subacute conditions. A correct diagnosis of PEA with imaging
      procedures enables conservative and successful outpatient management avoiding
      unnecessary surgical intervention and additional costs.

PMID- 22648259
TI  - Hydrogen therapy may be an effective and specific novel treatment for aplastic
      anemia.
AB  - Aplastic anemia (AA) is a rare bone marrow failure disorder with high mortality
      rate, which is characterized by pancytopenia and an associated increase in the
      risk of hemorrhage, infection, organ dysfunction and death. The oxidation
      phenomenon and/or the formation of free radicals have been suggested to be
      causally related to various hematological disorders, including aplastic anemia.
      TNF-alpha, IL-6, and IL-2 also play important roles in the pathogenesis of AA.
      Recent studies have provided evidence that hydrogen inhalation can selectively
      reduce cytotoxic oxygen radicals and exert antioxidant effects. It was also
      reported that hydrogen could suppress the levels of TNF-alpha and IL-6. Based on
      these findings, we hypothesize that hydrogen therapy may be an effective, simple,
      economic and novel strategy in the treatment of aplastic anemia.

PMID- 22648260
TI  - Cyclic fatigue resistance of Mtwo NiTi rotary instruments used by experienced and
      novice operators--an in vivo and in vitro study.
AB  - BACKGROUND: The aim of the present study was to evaluate the cyclic fatigue
      resistance of Mtwo NiTi rotary instruments after clinical use by 1 experienced
      and 1 novice operator. MATERIAL/METHODS: Cyclic fatigue testing of instruments
      was performed on tapered artificial canals with a 5 mm radius of curvature and 60
      degrees  angle of curvature. Twenty Mtwo instruments for each size were selected
      and divided into 2 groups: group A consisted of 10 instruments of each size used
      for shaping 10 root canals in molar teeth of patients by an experienced operator;
      group B consisted of 10 instruments of each size used for shaping 10 root canals
      in molar teeth of patients by a novice operator. Instruments were rotated until
      fracture occurred and the numbers of cycles to failure (NCF) were recorded. Data
      obtained were subjected to an independent sample t-test to determine statistical
      differences. The significance was determined at a 95% confidence level. RESULTS:
      No statistically significant difference (P<0.05) was noted between the
      instruments of groups A and B for all sizes. More instruments with visible signs
      of plastic deformation were identified for the novice operator. CONCLUSIONS: The
      clinical use of Mtwo NiTi rotary instruments by a novice operator did not
      significantly affect the cyclic fatigue resistance when compared with the control
      group of the same instrument sizes used by an experienced operator. It can be
      concluded that novice operators can use these instruments safely under the
      recommended technical guidelines.

PMID- 22648261
TI  - New quantitative patterns of the growing trachea in human fetuses.
AB  - BACKGROUND: Rapid progress in perinatal medicine has resulted in numerous tracheo
      bronchial interventions on fetal and neonatal airways. The present study was
      performed to compile normative data for tracheal dimensions at varying
      gestational ages. MATERIAL/METHODS: Using anatomical dissection, digital image
      analysis (NIS-Elements BR 3.0) and statistical analysis (Wilcoxon signed-rank
      test, Student's t test, one-way ANOVA, post-hoc Bonferroni test, linear and
      nonlinear regression analysis) a range of the 4 variables (length in mm, middle
      external transverse diameter in mm, proximal internal cross-sectional area in
      mm2, internal volume in mm3) for the trachea in 73 spontaneously aborted human
      fetuses (39 male, 34 female) aged 14-25 weeks was examined. RESULTS: No
      significant male-female differences were found (P>0.05). The length ranged from
      10.37+/-2.15 to 26.54+/-0.26 mm as y=-65.098 + 28.796 * ln (Age) +/-1.794
      (R2=0.82). The middle external transverse diameter varied from 2.53+/-0.09 to
      5.09+/-0.42 mm with the model y=-11.020 + 5.049 * ln (Age) +/-0.330 (R2=0.81).
      The trachea indicated a proportional evolution because the middle external
      transverse diameter-to-length ratio was stable (0.23+/-0.03). The proximal
      internal cross-sectional area rose from 1.46+/-0.04 to 5.76+/-1.04 mm2 as y=
      3.562 + 0.352 * Age +/-0.519 (R2=0.76). The internal volumetric growth from
      11.89+/-2.49 to 119.63+/-4.95 mm3 generated the function y=-135.248 + 9.919 * Age
      +/-10.478 (R2=0.86). CONCLUSIONS: The growth in both length and middle external
      transverse diameter of the trachea follows logarithmic functions, whereas growth
      of both its proximal internal cross-sectional area and internal volume follow
      linear functions. The length and middle external transverse diameter of the
      trachea develop proportionally to each other. The tracheal dimensions may be
      helpful in the prenatal diagnosis and monitoring of tracheal malformations and
      obstructive anomalies of the upper respiratory tract.

PMID- 22648262
TI  - Application of diffusion tensor imaging (DTI) in pathological changes of the
      spinal cord.
AB  - We review the current knowledge concerning clinical applications of the advanced
      technique of magnetic resonance imaging (MRI): diffusion tensor imaging (DTI) of
      the spinal cord. Due to technical difficulties, DTI has rarely been used in
      spinal cord diseases. However, in our opinion it is potentially a very useful
      method in diagnosis of the different pathological processes of the spinal cord
      and spinal canal. We discuss the physical principles and technical aspects of
      DTI, as well as current and future applications. DTI seems to be a very promising
      method for assessment of spinal cord trauma, spinal canal tumors, degenerative
      myelopathy, as well as demyelinating and infectious diseases of the spinal cord.
      DTI enables both qualitative and quantitative (by measuring of the fractional
      anisotropy and apparent diffusion coefficient parameters) assessment of the
      spinal cord. The particular applications are illustrated by the examples provided
      in this article.

PMID- 22648263
TI  - The role of human endogenous retroviruses in the pathogenesis of autoimmune
      diseases.
AB  - This paper presents a new, recently formulated theory, which concerns the
      etiopathological process of autoimmune diseases. This theory takes into account
      the existence in the human genome, since approximately 40 million years, of so
      called human endogenous retroviruses (HERVs), which are transmitted to
      descendants "vertically" by the germ cells. It was recently established that
      these generally silent sequences perform some physiological roles, but
      occasionally become active and influence the development of some chronic diseases
      like diabetes, some neoplasms, chronic diseases of the nervous system (eg,
      sclerosis multiplex), schizophrenia and autoimmune diseases. We present a short
      synopsis of immunological processes involved in the pathogenesis of autoimmune
      diseases, such as molecular mimicry, epitope spreading and activation of the
      superantigen. We then focus on experimental findings related to systemic lupus
      erythematosus, rheumatoid arthritis, Sjogren's syndrome and some diseases of
      hepar and otorhinal tissues. We conclude the outline of this new model of the
      development of chronic diseases and indicate the conclusions important for the
      teaching of the basis of pathology.

PMID- 22648264
TI  - Orthopedics and biofilm--what do we know? A review.
AB  - Bacteria have been found to grow predominantly in biofilms. The initial stage
      includes the attachment of bacteria to the substratum. Bacterial growth and
      division then leads to the colonization of the surrounding area and the formation
      of the biofilm. The environment in a biofilm is not homogeneous; the bacteria in
      a multispecies biofilm are not randomly distributed, but rather are organized to
      best meet their needs. Although there is an initial understanding on the
      mechanisms of biofilm-associated antimicrobial resistance, this topic is still
      under investigation. A variety of approaches are being explored to overcome
      biofilm-associated antimicrobial resistance. A greater understanding of biofilm
      processes should lead to novel, effective control strategies for biofilm control
      and a resulting improvement in patient management.

PMID- 22648266
TI  - Genetically elevated levels of circulating triglycerides and brachial-ankle pulse
      wave velocity in a Chinese population.
AB  - Elevated levels of circulating triglycerides and increased arterial stiffness are
      associated with cardiovascular disease. Numerous studies have reported an
      association between levels of circulating triglycerides and arterial stiffness.
      We used Mendelian randomization to test whether this association is causal. We
      investigated the association between circulating triglyceride levels, the
      apolipoprotein A-V (ApoA5) -1131T>C single nucleotide polymorphism and brachial
      ankle pulse wave velocity (baPWV) by examining data from 4421 subjects aged 18-74
      years who were recruited from the Chinese population. baPWV was significantly
      associated with the levels of circulating triglycerides after adjusting for age,
      sex, body mass index (BMI), systolic blood pressure, heart rate, waist-to-hip
      ratio, antihypertensive treatment and diabetes mellitus status. The -1131C allele
      was associated with a 5% (95% confidence interval 3-8%) increase in circulating
      triglycerides (adjusted for age, sex, BMI, waist-to-hip ratio, diabetes mellitus
      and antihypertensive treatment). Instrumental variable analysis showed that
      genetically elevated levels of circulating triglycerides were not associated with
      increased baPWV. These results do not support the hypothesis that levels of
      circulating triglycerides have a causal role in the development of arterial
      stiffness.

PMID- 22648265
TI  - Ophthalmic transplantology: posterior segment of the eye--part II.
AB  - BACKGROUND: Transplants of the retina are among the new strategies being used in
      the treatment of genetic and degenerative macular diseases. Moreover, various
      cell cultures are being tested to treat retinal disorders. MATERIAL/METHODS:
      Literature dated from 2004 to 2011 was comprehensively examined via Medline and
      PubMed searches for the following terms: auto-, homo-, heterologous
      transplantation, retina, stem cells, cultivated cells. RESULTS: Tissue and cell
      therapy of retinal diseases are reviewed, including full-thickness retina/retinal
      pigment epithelium (RPE)/choroid graft; full and partial thickness RPE/choroid
      complex grafts; RPE/Bruch membrane complex graft; and RPE, iris pigment
      epithelium and stem cell grafts. Recommendations for transplants, as well as the
      benefits and weaknesses of specific techniques in retina transplants, are
      discussed. CONCLUSIONS: Auto- and allogenic transplants of a full or partial
      thickness retina/RPE/ Bruch membrane/choroid complex represent an alternative
      treatment offered to patients with some macular diseases. Stem cell
      transplantation to reconstruct and regenerate the macula requires further
      biomolecular and animal research studies.

PMID- 22648268
TI  - An update on the genetics of pheochromocytoma.
AB  - Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine
      tumors. About 30% or more of them are thought to be of inherited origin due to
      germ-line mutations in at least 10 well-characterized genes. There are data
      linking specific genotypes of these tumors to specific locations, typical
      biochemical phenotypes or future clinical behaviors. Conversely, clinical
      features, catecholamine production and immunohistochemistry evaluation can help
      with the proper order of genetic testing for PHEO and PGL. The identification of
      a germ-line mutation can lead to an early diagnosis, appropriate treatment,
      regular surveillance and better prognosis not only for the patient but also for
      their family members. Moreover, the latest discoveries in molecular pathogenesis
      of these tumors will provide an important basis for future personalized therapy.

PMID- 22648269
TI  - Multisite validation study to determine performance characteristics of a 92-gene
      molecular cancer classifier.
AB  - PURPOSE: Accurate tumor classification is essential for cancer management as
      patient outcomes improve with use of site- and subtype-specific therapies.
      Current clinicopathologic evaluation is varied in approach, yet standardized
      diagnoses are critical for determining therapy. While gene expression-based
      cancer classifiers may potentially meet this need, imperative to determining
      their application to patient care is validation in rigorously designed studies.
      Here, we examined the performance of a 92-gene molecular classifier in a large
      multi-institution cohort. EXPERIMENTAL DESIGN: Case selection incorporated
      specimens from more than 50 subtypes, including a range of tumor grades,
      metastatic and primary tumors, and limited tissue samples. Formalin-fixed,
      paraffin-embedded tumors passed pathologist-adjudicated review between three
      institutions. Tumor classification using a 92-gene quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) assay was conducted on blinded
      tumor sections from 790 cases and compared with adjudicated diagnoses. RESULTS:
      The 92-gene assay showed overall sensitivities of 87% for tumor type [95%
      confidence interval (CI), 84-89] and 82% for subtype (95% CI, 79-85). Analyses of
      metastatic tumors, high-grade tumors, or cases with limited tissue showed no
      decrease in comparative performance (P = 0.16, 0.58, and 0.16). High specificity
      (96%-100%) was showed for ruling in a primary tumor in organs commonly harboring
      metastases. The assay incorrectly excluded the adjudicated diagnosis in 5% of
      cases. CONCLUSIONS: The 92-gene assay showed strong performance for accurate
      molecular classification of a diverse set of tumor histologies. Results support
      potential use of the assay as a standardized molecular adjunct to routine
      clinicopathologic evaluation for tumor classification and primary site diagnosis.

PMID- 22648267
TI  - Polymorphisms in the serum- and glucocorticoid-inducible kinase 1 gene are
      associated with blood pressure and renin response to dietary salt intake.
AB  - Serum- and glucocorticoid-inducible kinase 1 (SGK1) has a central role in
      epithelial sodium channel (ENaC)-dependent Na(+) transport in the distal nephron.
      We hypothesized that SGK1 gene variants may contribute to the effect of dietary
      salt intake on blood pressure (BP) in humans with hypertension, and
      consequentially influence renin-angiotensin-aldosterone (RAA) system activity.
      Our study population included 421 hypertensive Caucasian participants of the
      HyperPath group who had completed a dietary salt protocol with measurement of BP
      and RAA system activity. Three SGK1 tagging single nucleotide polymorphisms
      (SNPs) from the HapMap CEU population captured the genetic variation in the SGK1
      region. Assuming an additive genetic model, two SNPs (rs2758151 and rs9402571)
      were associated with BP and plasma renin activity (PRA) effects of dietary salt
      intake. Major alleles were associated with higher systolic BP on high salt and
      decreased PRA on low salt. In contrast, low salt neutralized genotype
      differences. Similar, non-significant trends were observed in a normotensive
      population (N=152). Genotype was also associated with two salt-sensitive subtypes
      of hypertension. SGK1 genetic variants are associated with salt sensitivity of BP
      and PRA in human hypertension. Genotype status at these SGK1 variants may
      identify individuals prone to salt-sensitive hypertension.

PMID- 22648270
TI  - Antitumor activity of targeted and cytotoxic agents in murine subcutaneous tumor
      models correlates with clinical response.
AB  - PURPOSE: Immunodeficient mice transplanted with subcutaneous tumors (xenograft or
      allograft) are widely used as a model of preclinical activity for the discovery
      and development of anticancer drug candidates. Despite their widespread use,
      there is a widely held view that these models provide minimal predictive value
      for discerning clinically active versus inactive agents. To improve the
      predictive nature of these models, we have carried out a retrospective population
      pharmacokinetic-pharmacodynamic (PK-PD) analysis of relevant xenograft/allograft
      efficacy data for eight agents (molecularly targeted and cytotoxic) with known
      clinical outcome. EXPERIMENTAL DESIGN: PK-PD modeling was carried out to first
      characterize the relationship between drug concentration and antitumor activity
      for each agent in dose-ranging xenograft or allograft experiments. Next,
      simulations of tumor growth inhibition (TGI) in xenografts/allografts at
      clinically relevant doses and schedules were carried out by replacing the murine
      pharmacokinetics, which were used to build the PK-PD model with human
      pharmacokinetics obtained from literature to account for species differences in
      pharmacokinetics. RESULTS: A significant correlation (r = 0.91, P = 0.0008) was
      observed between simulated xenograft/allograft TGI driven by human
      pharmacokinetics and clinical response but not when TGI observed at maximum
      tolerated doses in mice was correlated with clinical response (r = 0.36, P =
      0.34). CONCLUSIONS: On the basis of these analyses, agents that led to greater
      than 60% TGI in preclinical models, at clinically relevant exposures, are more
      likely to lead to responses in the clinic. A proposed strategy for the use of
      murine subcutaneous models for compound selection in anticancer drug discovery is
      discussed.

PMID- 22648271
TI  - FGFR4 blockade exerts distinct antitumorigenic effects in human embryonal versus
      alveolar rhabdomyosarcoma.
AB  - PURPOSE: Rhabdomyosarcoma (RMS) is a malignancy with features of skeletal muscle,
      and the most common soft tissue sarcoma of childhood. Survival for high-risk
      groups is approximately 30% at 5 years and there are no durable therapies
      tailored to its genetic aberrations. During genetic modeling of the common RMS
      variants, embryonal RMS (eRMS) and alveolar RMS (aRMS), we noted that the
      receptor tyrosine kinase (RTK) fibroblast growth factor receptor 4 (FGFR4) was
      upregulated as an early event in aRMS. Herein, we evaluated the expression of
      FGFR4 in eRMS compared with aRMS, and whether FGFR4 had similar or distinct roles
      in their tumorigenesis. EXPERIMENTAL DESIGN: Human RMS cell lines and tumor
      tissue were analyzed for FGFR4 expression by immunoblot and immunohistochemistry.
      Genetic and pharmacologic loss-of-function of FGFR4 using virally transduced
      short hairpin RNA (shRNA) and the FGFR small-molecule inhibitor PD173074,
      respectively, were used to study the role of FGFR4 in RMS cell lines in vitro and
      xenografts in vivo. Expression of the antiapoptotic protein BCL2L1 was also
      examined. RESULTS: FGFR4 is expressed in both RMS subtypes, but protein
      expression is higher in aRMS. The signature aRMS gene fusion product, PAX3-FOXO1,
      induced FGFR4 expression in primary human myoblasts. In eRMS, FGFR4 loss-of
      function reduced cell proliferation in vitro and xenograft formation in vivo. In
      aRMS, it diminished cell survival in vitro. In myoblasts and aRMS, FGFR4 was
      necessary and sufficient for expression of BCL2L1 whereas in eRMS, this induction
      was not observed, suggesting differential FGFR4 signaling. CONCLUSION: These
      studies define dichotomous roles for FGFR4 in RMS subtypes, and support further
      study of FGFR4 as a therapeutic target.

PMID- 22648272
TI  - Defective epidermal innate immunity and resultant superficial dermatophytosis in
      adult T-cell leukemia/lymphoma.
AB  - PURPOSE: Superficial dermatophytosis is quite commonly seen in patients with
      adult T-cell leukemia/lymphoma (ATLL), as approximately 50% of the patients
      develop cutaneous mycotic infections. Because superficially infected fungi in the
      stratum corneum of the epidermis cannot directly contact with T cells
      infiltrating in the upper dermis, some perturbation of epidermal innate immunity
      has been postulated. Interleukin (IL)-17-producing helper T cells (Th17) can
      induce the keratinocyte production of antimicrobial peptides such as human beta
      defensin (HBD)-2 and LL-37, which play an essential role in cutaneous innate
      immunity. EXPERIMENTAL DESIGN: We investigated the frequency of circulating Th17
      cells, serum levels of cytokines, and epidermal expression of HBD-1, 2, 3, and LL
      37 in ATLL patients with or without superficial dermatophytosis. RESULTS: The
      frequency of peripheral Th17 cells and the serum level of IL-17 was significantly
      decreased in ATLL patients, whereas the serum IL-10 and TGF-beta1 levels were
      increased as compared with healthy controls. Furthermore, ATLL patients with
      dermatophytosis had higher IL-10 and TGF-beta1 levels and lower IL-17 levels than
      did those without dermatophytosis. Immunohistochemical study revealed that the
      epidermal expression of both HBD-2 and LL-37 were significantly lower in ATLL
      patients with dermatophytosis than in non-ATLL patients with dermatophytosis.
      CONCLUSIONS: Taken together, these results suggest that the keratinocyte
      production of antimicrobial peptides promoted by Th17 cells is reduced in ATLL
      patients, leading to the perturbed innate immunity and the frequent occurrence of
      superficial dermatophytosis.

PMID- 22648273
TI  - Molecular pathways: dysregulated glutamatergic signaling pathways in cancer.
AB  - The neurotransmitter glutamate interacts with glutamate receptor proteins,
      leading to the activation of multiple signaling pathways. Dysfunction in the
      glutamatergic signaling pathway is well established as a frequent player in
      diseases such as schizophrenia, Alzheimer disease, and brain tumors (gliomas).
      Recently, aberrant functioning of this pathway has also been shown in melanoma.
      In both glioma and melanoma, glutamate secretion stimulates tumor growth,
      proliferation, and survival through activation of the mitogen-activated protein
      kinase and phosphoinositide 3-kinase/Akt pathways. In the future, extracellular
      glutamate levels and glutamatergic signaling may serve as biological markers for
      tumorigenicity and facilitate targeted therapy for melanoma. .

PMID- 22648274
TI  - Tandem one-pot synthesis of flavans by recyclable silica-HClO4 catalyzed
      Knoevenagel condensation and [4 + 2]-Diels-Alder cycloaddition.
AB  - An efficient one-pot multi-component synthesis of flavans using perchloric acid
      supported on silica as a recyclable heterogeneous catalyst has been described.
      This is the first report of direct one-step construction of a flavan skeleton
      from a phenolic precursor. The method involves a Knoevenagel-type condensation
      leading to in situ formation of transient O-quinone methide which further
      undergoes [4 + 2]-Diels-Alder cycloaddition with styrene to yield a flavan
      skeleton. The method provides easy access to a wide range of bio-active natural
      products viz. flavonoids, anthocyanins and catechins.

PMID- 22648277
TI  - Drug-induced life-threatening potassium disturbances detected by a
      pharmacovigilance program from laboratory signals.
AB  - PURPOSE: Detection and reporting of drug-induced life-threatening potassium
      disturbances and the study of associated factors under a Pharmacovigilance
      Program using Laboratory Signals at a Hospital (PPLSH) during a 2-year period.
      METHODS: All serum potassium levels <2 mmol/l or >7 mmol/l detected at admission
      to the hospital, including those of patients who died in the emergency ward or
      during hospitalization, were monitored prospectively from January 2009 through to
      December 2010. The incidence rate of each etiology of potassium disturbances was
      calculated. Factors associated with drug-induced potassium disturbances were
      detected using a multiple logistic regression model. RESULTS: The incidence of
      true life-threatening drug-induced hyper- and hypokalemia events was 3 and 4.32
      (Poisson 95 % confidence interval 1.62-10.24), respectively, per 10,000
      admissions. Of the severe potassium disturbances, 32.3 % were drug-induced, and
      23 % were lethal. We identified previously undescribed pharmacological causes of
      hyperkalemia (risedronate, doxazosin) and hypokalemia (acyclovir, teicoplanin,
      cefepime, meropenem, dexketoprofen colistimethate). Significant predictor factors
      associated with drug-induced hyperkalemia were the use of polypharmacy (>5
      drugs), age (>74 years), sex (female) and kidney disease (glomerular filtration
      rate <60 ml/min) with the presence of >=4 comorbid conditions. The only predictor
      of drug-induced hypokalemia was the use of >5 drugs. The triggering factor
      associated with drug-induced hyperkalemia and hypokalemia was azotemia and
      hypoalbuminemia, respectively. CONCLUSIONS: Drug-induced life-threatening
      potassium disturbances remain a relevant problem. Potential strategies for
      prevention are to avoid polypharmacy, early discontinuation of treatment of drugs
      causing hyperkalemia or nephrotoxicity in cases of various clinical situations
      (cardiac descompensation, infection, hypovolemia) or obstructive causes, and
      insistence on albumin control during hospitalization.

PMID- 22648278
TI  - Interaction between amorolfine and acenocoumarol.

PMID- 22648276
TI  - Cardiac vulnerability to ischemia/reperfusion injury drastically increases in
      late pregnancy.
AB  - Although the murine late pregnant (LP) heart is speculated to be a better
      functioning heart during physiological conditions, the susceptibility of LP
      hearts to I/R injury is still unknown. The aims of this study were to investigate
      the cardiac vulnerability of LP rodents to ischemia/reperfusion (I/R) injury and
      to explore its underlying mechanisms. In vivo female rat hearts [non-pregnant
      (NP) or LP] or ex vivo Langendorff-perfused mouse hearts were subjected to I/R.
      The infarct size was approximately fourfold larger in LP animals compared with NP
      both in vivo and ex vivo. The heart functional recovery was extremely poor in LP
      mice compared with NP (~10% recovery in LP vs. 80% recovery in NP at the end of
      reperfusion, P < 0.01). Interestingly, the poor functional recovery and the
      larger infarct size in LP were partially restored one day post-partum and almost
      fully restored 1 week post-partum to their corresponding NP levels. Mitochondrial
      respiratory function and the threshold for opening of the mitochondrial
      permeability transition pore were significantly lower in LP compared with NP when
      they both were subjected to myocardial I/R injury [Respiratory control ratio =
      1.9 +/- 0.1 vs. 4.0 +/- 0.5 in NP, P < 0.05; calcium retention capacity (CRC) =
      167 +/- 10 vs. 233 +/- 18 nmol/mg protein in NP, P < 0.01]. Cardiac reactive
      oxygen species (ROS) generation, as well mitochondrial superoxide production, was
      approximately twofold higher in LP compared with NP following I/R. The
      phosphorylation levels of Akt, ERK1/2, and STAT3, but not GSK3beta, were
      significantly reduced in the hearts from LP subjected to I/R. In conclusion,
      increased mitochondrial ROS generation, decreased CRC as well as impaired
      activation of Akt/ERK/STAT3 at reperfusion are the possible underlying mechanisms
      for higher vulnerability of LP hearts to I/R.

PMID- 22648281
TI  - Catalysis by metallic nanoparticles in aqueous solution: model reactions.
AB  - Catalysis by metallic nanoparticles is certainly among the most intensely studied
      problems in modern nanoscience. However, reliable tests for catalytic performance
      of such nanoparticles are often poorly defined, which makes comparison and
      benchmarking rather difficult. We tackle in this tutorial review a subset of well
      studied reactions that take place in aqueous phase and for which a comprehensive
      kinetic analysis is available. Two of these catalytic model reactions are under
      consideration here, namely the reduction of (i) p-nitrophenol and (ii)
      hexacyanoferrate (iii), both by borohydride ions. Both reactions take place at
      the surface of noble metal nanoparticles at room temperature and can be
      accurately monitored by UV-vis spectroscopy. Moreover, the total surface area of
      the nanoparticles in solution can be known with high precision and thus can be
      directly used for the kinetic analysis. Hence, these model reactions represent
      cases of heterogeneous catalysis that can be modelled with the accuracy typically
      available for homogeneous catalysis. Both model reactions allow us to discuss a
      number of important concepts and questions, namely the dependence of catalytic
      activity on the size of the nanoparticles, electrochemistry of nanoparticles,
      surface restructuring, the use of carrier systems and the role of diffusion
      control.

PMID- 22648279
TI  - Do immigrants from Turkey, Pakistan and Ex-Yugoslavia with newly diagnosed type 2
      diabetes initiate recommended statin therapy to the same extent as Danish-born
      residents? A nationwide register study.
AB  - PURPOSE: To explore whether newly diagnosed type 2 diabetes patients without
      previous cardiovascular disease (CVD) initiate preventive statin therapy
      regardless of ethnic background. METHODS: Using nationwide individual-level
      registers, we followed a cohort of Danish-born residents and immigrants from
      Turkey, Pakistan and Ex-Yugoslavia, all without previous diabetes or CVD, during
      the period 2000-2008 for first dispensing of oral glucose-lowering medication
      (GLM), first dispensing of statins and register-markers of CVD (N = 3,764,620).
      Logistic regression analyses were used to test whether the odds ratios (ORs) of
      early statin therapy initiation (within 180 days after first GLM dispensing) are
      the same regardless of ethnic background. While age and gender were included as
      confounders in the basic model, income was included in the second model as a
      potential mediating variable. RESULTS: Compared to native Danes, the ORs for
      early statin therapy were 0.68 (95 % confidence interval 0.50-0.92], 0.67 (0.56
      0.81) and 0.56 (0.44-0.71) for Ex-Yugoslavians, Turks and Pakistanis,
      respectively. The differences remained largely unchanged after adjusting for
      income and tended to be accentuated when the threshold period was extended. The
      ORs of women initiating therapy (compared to native Danes) were 0.56 (0.35-0.90),
      0.60 (0.46-0.78) and 0.48 (0.32-0.72) for Ex-Yugoslavians, Turks and Pakistanis,
      respectively, and those for men were 0.78 (0.52-1.17), 0.74 (0.58-0.95) and 0.60
      (0.44-0.83), respectively. CONCLUSIONS: Immigrants from Turkey, Pakistan and Ex
      Yugoslavia with type 2 diabetes were less likely to initiate statin therapy than
      Danish-born residents-despite a similar or even higher risk of CVD. The treatment
      inequities associated with ethnicity were more pronounced in women than men.

PMID- 22648280
TI  - The effect of operational stressors on ibuprofen pharmacokinetics.
AB  - PURPOSE: To determine whether two of the major operational stressors associated
      with military missions in Afghanistan: dry heat and long durations of soldier
      patrol (SP), alter the pharmacokinetics of ibuprofen. METHODS: Thirteen healthy
      and physically fit participants (19-32 years) were randomized to a four-arm
      crossover study, as follows: Arm 4 consisted of a simulated 2.5 h SP on a
      treadmill set at 4.5 km/h, 2% incline (15-min walk/5-min rest cycle) in a
      climatic chamber set to 42 degrees C, 9% relative humidity. Arm 3 was similar to
      arm 4 but at room temperature, and arms 1 and 2 were sham SP to 3 and 4,
      respectively. For the final 2.5 h, participants remained in a semi-supine
      position. Each participant orally administered one 400-mg Advil Liqui-Gel(r)
      capsule. Blood samples were drawn over time and analyzed for (R)-ibuprofen and
      (S)-plasma ibuprofen concentrations using UPLC/MS/MS. Concentration-time data
      were analyzed by compartmental methods. RESULTS: Exercise significantly decreased
      the t(1/2abs) (h) of (S)-ibuprofen (0.26 to 0.17; p = 0.015) and T(max) (h) for
      both (R)-ibuprofen (0.97 to 0.73; p = 0.008) and (S)-ibuprofen (1.13 to 0.84; p =
      0.005). Values for t(lag) (h) also decreased with exercise for both (R)-ibuprofen
      (0.38 to 0.22; p = 0.005), and (S)-ibuprofen (0.39 to 0.23; p = 0.001).
      CONCLUSIONS: Exercise stress had a significant impact on the absorption profile
      of (R)- and (S)-ibuprofen. Excessive self-administration rate and dose may not be
      due to the military operational stressors of heat and soldier presence patrol.

PMID- 22648282
TI  - Recommendations for fertility preservation in patients with lymphoma, leukemia,
      and breast cancer.
AB  - Fertility issues should be addressed to all patients in reproductive age before
      cancer treatment. In men, cryopreservation of sperm should be offered to all
      cancer patients in reproductive age regardless of the risk of gonadal failure. In
      women, the recommendation of fertility preservation should be individualized
      based on multiple factors such as the urgency of treatment, the age of the
      patient, the marital status, the regimen and dosage of cancer treatment.

PMID- 22648283
TI  - Clinical data for 185 infertile Iranian men with Y-chromosome microdeletion.
AB  - Detection of Y-chromosome microdeletion is useful to obtain reliable genetic
      information for assisted reproductive techniques, thus avoiding unnecessary
      treatment and vertical transmission of genetic defects. PURPOSES: This research
      was conducted over a six-year period to analyze clinical data, somatic
      cytogenetic abnormalities, and types of microdeletions in men with fertility
      disorders in Iran. METHODS AND PATIENTS: A total of 3654 infertile men were
      included in this study. Semen samples were analyzed according to standard
      methods. Conventional chromosomal karyotyping was used to analyze chromosome
      abnormalities. Polymerase chain reaction (PCR) amplification using nine specific
      sequence-tagged sites (STS) was used to detect AZF microdeletions. RESULTS: Out
      of the 3654 patients who were analyzed, AZF region microdeletions were detected
      in 185 cases (5.06 %). Karyotype analysis was available for 157 men and among
      them abnormal karyotypes were found in 51 cases (32.48 %). One hundred and forty
      seven cases with Yq microdeletions suffered from azoospermia and 38 from severe
      oligozoospermia. Our data show that the most frequent microdeletions were in the
      AZFc region, followed by the AZFb + c + d, AZFb + c, AZFb, AZFa, and AZF a + c
      regions. CONCLUSION: The study has confirmed that the detection of microdeletions
      in the AZF region is significant from a diagnostic viewpoint. It is also useful
      to obtain reliable genetic information from infertile men to determine the
      etiology of the deletions, and to avoid unnecessary treatments and vertical
      transmission of genetic defects.

PMID- 22648284
TI  - Efficient combined FISH and PRINS technique for detection of DAZ microdeletion in
      human sperm.
AB  - Intracytoplasmic sperm injection (ICSI) now offers an effective therapeutic
      option for men with male infertility and is believed to allow transmission of
      genetically determined infertility to the male offspring. Transmission of DAZ
      (Deleted in Azoospermia) microdeletion is one of the major concerns for oligo and
      severe oligozoospermia patients. Screening of the Y chromosome microdeletion in
      the diagnostic work-up of infertile men is mainly done using polymerase chain
      reaction (PCR) on blood leukocytes. However, there are evidences showing that
      presence of DAZ in somatic cells might not be indicative of its presence in germ
      cell lineage. In this report we are going to describe a combined Primed in situ
      labeling (PRINS) and fluorescence in situ hybridization (FISH) technique to show
      the localization of DAZ gene as well as Y chromosome centromere on sperm nuclei.
      PRINS is a combination of FISH and in situ polymerization provides another
      approach for in situ chromosomal detection. In the present study the PRINS
      primers specific for DAZ genes and traditional direct labeled centromere FISH
      probes for Y and X chromosomes were used in order to simultaneously detect DAZ
      genes and sex chromosome aneuploidy in sperm samples.

PMID- 22648285
TI  - A quantitative diagnostic method for oral mucous precancerosis by Rose Bengal
      fluorescence spectroscopy.
AB  - A novel in vivo fluorescence spectroscopic diagnostic method has been developed
      in an animal model to make a quantified precancer diagnosis. In the study, 40
      golden hamsters were randomly divided into four groups (groups A, B, C, and D),
      with group A being the control group and the other three groups being inducted at
      different precancer stages. A 1% Rose Bengal (RB) solution was used for the
      fluorescence spectroscopic diagnosis. A parameter K defined as K = I(RB)/I(auto)
      was introduced to reflect the amount of RB in the tissue, where I(RB) and I(auto)
      represent the fluorescence peak intensity of the RB in the tissue and the
      autofluorescence intensity of tissue at 580 nm, respectively. The average K
      values of the four groups were calculated and statistically analyzed by analysis
      of variance (ANOVA), which revealed statistically significant differences within
      each group as well as between groups (p < 0.001). After analysis by Clementine
      11.1 C&R Tree modeling (CART), the following diagnostic criteria were set:
      normal, K <= 8.91; simple hyperplasia, 8.91 < K <= 41.92; mild dysplasia, 41.92 <
      K <= 70.79; moderate and severe dysplasia, K >70.79. The sensitivity and
      specificity to detect precancerous lesions compared with scalpel biopsy were
      calculated. The results of this study showed that the spectrofluorometric method
      mediated by RB could accurately discriminate different precancer stages.

PMID- 22648286
TI  - Implementation of self-rostering (the PRIO-project): effects on working hours,
      recovery, and health.
AB  - OBJECTIVES: The aim of this study was to (i) investigate the consequences of self
      rostering for working hours, recovery, and health, and (ii) elucidate the
      mechanisms through which recovery and health are affected. METHODS: Twenty eight
      workplaces were allocated to either an intervention or reference group.
      Intervention A encompassed the possibility to specify preferences for starting
      time and length of shift down to 15 minutes intervals. Interventions B and C
      included the opportunity to choose between a number of predefined duties.
      Questionnaires (N=840) on recovery and health and objective workplace reports of
      working hours (N=718) were obtained at baseline and 12 months later. The
      interaction term between intervention and time was tested in mixed models and
      multinomial logistic regression models. RESULTS: The odds ratio (OR) of having
      short [OR 4.8, 95 % confidence interval (95% CI) 1.9-12.3] and long (OR 4.8, 95%
      CI 2.9-8.0) shifts increased in intervention A. Somatic symptoms (beta= -0.10,
      95% CI -0.19- -0.02) and mental distress (beta= -0.13, 95% CI -0.23- -0.03)
      decreased, and sleep (beta= 1.7, 95% CI 0.04-0.30) improved in intervention B,
      and need for recovery was reduced in interventions A (beta= -0.17, 95% CI -0.29- 
      0.04) and B (beta= -0.17, 95% CI -0.27- -0.07). There were no effects on recovery
      and health in intervention C, and overall, there were no detrimental effects on
      recovery or health. The benefits of the intervention were not related to changes
      in working hours and did not differ by gender, age, family type, degree of
      employment, or working hour arrangements. CONCLUSIONS: After implementation of
      self-rostering, employees changed shift length and timing but did not compromise
      most recommendations for acceptable shift work schedules. Positive consequences
      of self-rostering for recovery and health were observed, particularly in
      intervention B where worktime control increased but less extensively than
      intervention A. The effect could not be statistically explained by changes in
      actual working hours.

PMID- 22648287
TI  - Effect of adding cervical facet joint injections in a multimodal treatment
      program for long-standing cervical myofascial pain syndrome with referral pain
      patterns of cervical facet joint syndrome.
AB  - PURPOSE: Cervical facet joint (CFJ) syndrome is a common disorder observed in
      chronic pain of the cervical region, especially in long-standing myofascial pain
      syndrome (MPS). This study aimed to investigate the effects of therapeutic CFJ
      injections on patients with long-standing cervical MPS with referral pain
      patterns of CFJ syndrome. METHODS: Four hundred patients presented with long
      standing cervical MPS with referral pain patterns of CFJ syndrome over a period
      of 6 months. A randomized clinical trial was performed wherein 200 patients
      (group 1) received therapeutic CFJ injections at bilateral C5/C6 and C6/C7 after
      diagnostic, controlled double-blind blocks. The same cointerventions, such as
      medication and a home exercise program, were simultaneously applied to patients
      in group 1 and the noninjection group (group N). Cervical range of motion (CROM),
      mean reduction of numeric rate scale (NRS) for pain, and comorbid tension-type
      headache were compared between groups during the 1-year follow-up period.
      Treatment duration and symptom-free periods were compared according to age group.
      RESULTS: Group 1 showed increased CROM, increased mean NRS pain reduction, and
      decreased incidence of combined tension-type headache compared with group N
      during the follow-up. Younger patients in group 1 required a shorter treatment
      cycle and experienced a longer symptom-free period. CONCLUSION: Addition of
      therapeutic CFJ injections to a multimodal treatment program is a useful
      therapeutic modality for patients, especially young patients, suffering from long
      standing MPS with referral pain of CFJ syndrome.

PMID- 22648288
TI  - Coronary CT angiography after stress testing: an efficient use of resources?
      Implications of the Advanced Cardiovascular Imaging Consortium (ACIC) results.
AB  - Coronary CT angiography (CCTA) has matured to be a fast noninvasive imaging test
      in the evaluation of coronary artery disease (CAD). It has demonstrated excellent
      accuracy for defining the presence and the severity of luminal coronary artery
      stenoses and is probably the best noninvasive test to reliably exclude
      atherosclerotic coronary disease. Furthermore, accumulating CCTA data indicate
      that it can identify individuals at risk for all-cause mortality. It is also well
      known that despite the wealth of data regarding diagnostic and prognostic values
      of stress testing in CAD, up to 10% of stress imaging studies are considered
      inconclusive, leading to subsequent invasive coronary angiography for definitive
      diagnosis often with negative results. Moreover, recent data indicate that up to
      30 % of patients undergoing angiography have no significant CAD despite a
      majority of them having had a prior stress test. Whether CCTA can serve as a cost
      effective methodology to invasive angiography has been a source of active
      research. In this context, we will discuss the implications of the recently
      published data from the Advanced Cardiovascular Imaging Consortium registry
      looking at the use of CCTA after stress testing in Michigan.

PMID- 22648289
TI  - Effect of uric acid lowering therapy on the prevention of acute kidney injury in
      cardiovascular surgery.
AB  - PURPOSE: Serum uric acid (SUA) is a novel risk factor for acute kidney injury
      (AKI), which adversely affects renal blood flow autoregulation, glomerular
      filtration rate (GFR), and promotes inflammation and angiogenesis. This pilot
      study investigated the effect of lowering SUA therapy on AKI, by using
      traditional and non-traditional markers. MATERIALS AND METHODS: In this
      prospective, double-blind, placebo-controlled, randomized pilot trial, 26
      hyperuricemic patients undergoing cardiac surgery were randomized to receive
      rasburicase or placebo in the preoperative period. RESULTS: Subjects receiving
      rasburicase showed no difference in serum creatinine compared with the control
      group receiving placebo. Despite no difference in primary endpoint, the
      rasburicase group had less evidence of renal structural injury as reflected by
      urine neutrophil-associated lipocalin (uNGAL) concentrations, especially in
      subjects with higher SUA levels, more severe renal dysfunction (baseline GFR <=
      45 mL/min/1.73 m(2)) or heart failure (left ventricular ejection fraction <=45
      %). CONCLUSIONS: In this study, rasburicase showed no benefit on postoperative
      serum creatinine in hyperuricemic subjects undergoing cardiac surgery. However,
      the observation that markers of structural renal injury such as uNGAL tended to
      be lower in rasburicase-treated subjects suggests potential different effects of
      uricase treatment on hemodynamic alterations in renal function versus structural
      mechanisms of kidney injury.

PMID- 22648290
TI  - Diabetes and hypertension have become leading causes of CKD in Chinese elderly
      patients: a comparison between 1990-1991 and 2009-2010.
AB  - BACKGROUND: It is unclear whether any significant changes in the epidemiology of
      chronic kidney disease (CKD), possibly resulting from the exceedingly rapid
      economic development and the aggressive prevention and treatment of kidney
      diseases in the Chinese population, have occurred over the past two decades.
      METHODS: The medical records of 173 CKD patients from 1990-1991 and 956 patients
      from 2009-2010 were retrospectively analyzed. RESULTS: In patients from 1990
      1991, CKD occurred at an earlier age, with severely decreased kidney function. On
      average, these patients progressed to end-stage renal disease 4.5 years faster.
      Diabetes and hypertension have become the most common causes of CKD in elderly
      patients in 2009-2010 period, representing 39.5 % and 24.2 % of all CKD causes,
      respectively. In the 1990-1991 period, CKD was characterized by a high frequency
      of severe anemia in stage 4 and 5 patients. The mean arterial pressure in
      patients with CKD stage 4 and stage 5 decreased significantly in. Although the
      number of dyslipidemia patients in stage 4 and 5 was significantly higher in the
      2009-2010 period, there were no substantial differences in the average levels of
      serum triglycerides and total cholesterol in the two cohorts. Hypoproteinemia
      also became less common than before. The occurrence of cardiovascular events was
      significantly reduced in stage 4 and stage 5 patients in 2009-2010. CONCLUSIONS:
      Diabetes and hypertension have increased and become the leading causes of CKD in
      elderly Chinese patients. Improvement in the control of CKD complications has
      been significant, mainly regarding anemia, hypertension, dyslipidemia, and
      hypoproteinemia.

PMID- 22648291
TI  - Extraperitoneal laparoscopic retroperitoneal lymph node dissection after
      chemotherapy for nonseminomatous testicular germ-cell tumor: surgical and
      oncological outcomes.
AB  - PURPOSE: To assess the surgical and oncological outcomes of laparoscopic
      retroperitoneal lymph node dissection (RPLND) after chemotherapy. METHODS: Twenty
      patients with metastatic nonseminomatous testicular germ-cell tumor underwent
      extraperitoneal laparoscopic RPLND after chemotherapy. The procedure was not
      indicated for patients with a pre-chemotherapy mass larger than 5 cm. Morbidity
      and oncological outcome were reviewed retrospectively. Surgical complications
      were graded according to the Clavien classification system. RESULTS: Laparoscopic
      RPLND was completed in all patients, and there was no conversion to open surgery.
      The median operating time was 223 min (range, 137-399 min). The median blood loss
      was 20 ml (range, 10-520 ml). There were no intraoperative complications.
      Postoperatively, 4 patients (20 %) had prolonged lymphorrhea (grade I) and 9 (45
      %) had chyle leakage (grade I). Histological examination of the residual mass
      revealed necrosis in 16 (80 %) and the presence of teratoma with/without viable
      tumor in 4 (20 %). With a median follow-up of 45 months (range, 24-112), no
      patient has had disease recurrence. Normal antegrade ejaculation was preserved in
      all of the 14 patients studied. CONCLUSIONS: Extraperitoneal laparoscopic RPLND
      can be performed with acceptable morbidity and excellent cancer control in select
      patients. Surgeons should be aware of relatively high incidence of chyle leakage
      following this procedure.

PMID- 22648292
TI  - Pathological implications of areas of lower enhancement on contrast-enhanced
      computed tomography in renal-cell carcinoma: additional information for selecting
      candidates for surveillance protocols.
AB  - PURPOSE: Areas of lower enhancement on computed tomography are frequently seen in
      renal-cell carcinoma. We investigated whether tumor enhancement on the most
      prominent hypodense areas correlates with the nuclear grade and other pathologic
      variables. METHODS: From 2004 to 2009, all consecutive patients with a
      preoperative tomography who underwent radical or partial nephrectomy for renal
      cell carcinoma at our tertiary referral center were retrospectively analyzed.
      Enhancement of the entire tumor on the slice with most prominent areas of lower
      enhancement was determined. RESULTS: Forty-eight patients were included. Clear
      cell carcinoma comprised 91.6 %. Mean areas of lower enhancement for nuclear
      grade tumors 1-4 were 67.4, 38.7, 27.9, and 15.1 HU, respectively. Areas of lower
      enhancement negatively correlated with size, nuclear grade, T stage, and
      pathological stage. Tumors with extension beyond Gerota's fascia (10.5 vs. 35.9
      HU, p < 0.001) and positive surgical margins (21.2 vs. 34.8 HU, p = 0.04) had
      more prominent areas of lower enhancement than organ-confined tumors. When
      comparing nuclear grade 1-3 to nuclear grade 4 tumors, these areas were
      significantly lower in the later (36.5 vs. 15.1 HU, p < 0.001). Receiver
      operating characteristics curves for detecting nuclear grade 4 showed an area
      under the curve of 0.808 (95 % CI 0.659-0.957). CONCLUSIONS: Lower enhancement of
      the entire tumor at the point where hypodense tumor areas are more predominant on
      tomography is associated with higher nuclear grade and more advanced stage.

PMID- 22648293
TI  - Thermally responsive shuttling behavior of a pillar[6]arene-based [2]rotaxane.
AB  - A [2]rotaxane constructed from a per-ethylated pillar[6]arene as a wheel and a
      pyridinium derivative as an axle was prepared. The wheel segment of the per
      ethylated pillar[6]arene moved from one station to another along the axle as a
      result of thermal stimuli.

PMID- 22648294
TI  - Vitamin K intake and status are low in hemodialysis patients.
AB  - Vitamin K is essential for the activity of gamma-carboxyglutamate (Gla)-proteins
      including matrix Gla28 protein and osteocalcin; an inhibitor of vascular
      calcification and a bone matrix protein, respectively. Insufficient vitamin K
      intake leads to the production of non-carboxylated, inactive proteins and this
      could contribute to the high risk of vascular calcification in hemodialysis
      patients. To help resolve this, we measured vitamin K(1) and K(2) intake (4-day
      food record), and the vitamin K status in 40 hemodialysis patients. The intake
      was low in these patients (median 140 MUg/day), especially on days of dialysis
      and the weekend as compared to intakes reported in a reference population of
      healthy adults (mean K(1) and K(2) intake 200 MUg/day and 31 MUg/day,
      respectively). Non-carboxylated bone and coagulation proteins were found to be
      elevated in 33 hemodialysis patients, indicating subclinical hepatic vitamin K
      deficiency. Additionally, very high non-carboxylated matrix Gla28 protein levels,
      endemic to all patients, suggest vascular vitamin K deficiency. Thus, compared to
      healthy individuals, hemodialysis patients have a poor overall vitamin K status
      due to low intake. A randomized controlled trial is needed to test whether
      vitamin K supplementation reduces the risk of arterial calcification and
      mortality in hemodialysis patients.

PMID- 22648295
TI  - Activation of peroxisome proliferator-activated receptor-gamma coactivator 1alpha
      ameliorates mitochondrial dysfunction and protects podocytes from aldosterone
      induced injury.
AB  - Glomerular podocytes are highly specialized epithelial cells whose injury in
      glomerular diseases causes proteinuria. Since mitochondrial dysfunction is an
      early event in podocyte injury, we tested whether a major regulator of oxidative
      metabolism and mitochondrial function, the transcriptional coactivator peroxisome
      proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), affects
      podocyte damage. Aldosterone-induced injury decreased PGC-1alpha expression, and
      induced mitochondrial and podocyte damage in dose- and time-dependent manners.
      The suppression of endogenous PGC-1alpha by RNAi caused podocyte mitochondrial
      damage and apoptosis while its increase by infection with an adenoviral vector
      prevented aldosterone-induced mitochondrial malfunction and inhibited injury.
      Overexpression of the silent mating type information regulation 2 homolog 1, a
      gene upstream of PGC-1alpha, prevented aldosterone-induced mitochondrial damage
      and podocyte injury by upregulating PGC-1alpha at both the transcriptional and
      post-translational levels. Resveratrol, a SIRT1 activator, attenuated aldosterone
      induced mitochondrial malfunction and podocyte injury in vitro and in aldosterone
      infused mice in vivo. Hence, endogenous PGC-1alpha may be important for
      maintenance of mitochondrial function in podocytes under normal conditions.
      Activators of SIRT1, such as resveratol, may be therapeutically useful in
      glomerular diseases to promote and maintain PGC-1alpha expression and,
      consequently, podocyte integrity.

PMID- 22648298
TI  - Should mycophenolate mofetil replace cyclophosphamide as first-line therapy for
      severe lupus nephritis?
AB  - Available treatments for severe (class III, IV, and V) lupus nephritis (LN) have
      expanded greatly over the last 40 years. In the 1970s and 1980s, cyclophosphamide
      (CYC), in combination with glucocorticoids, gained favor as induction and
      maintenance therapy for severe LN. However, the adverse event profile of CYC led
      to the search for other medications for severe LN. Beginning in the late 1990 s,
      mycophenolate mofetil (MMF) was introduced as induction and maintenance therapy
      for severe LN. This review discusses the clinical trial results, pharmacology,
      cost-effectiveness, and adverse effect profiles of CYC compared to MMF for
      induction and maintenance therapy for severe LN. The authors conclude that MMF
      should be considered first-line induction and maintenance treatment therapy for
      severe LN, although CYC may have a place under specific clinical and economic
      circumstances.

PMID- 22648296
TI  - The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D
      catabolism, is reduced in chronic kidney disease.
AB  - Chronic kidney disease is characterized, in part, as a state of decreased
      production of 1,25-dihydroxyvitamin D (1,25(OH)(2)D); however, this paradigm
      overlooks the role of vitamin D catabolism. We developed a mass spectrometric
      assay to quantify serum concentration of 24,25-dihydroxyvitamin D
      (24,25(OH)(2)D), the first metabolic product of 25-hydroxyvitamin D (25(OH)D) by
      CYP24A1, and determined its clinical correlates and associated outcomes among 278
      participants with chronic kidney disease in the Seattle Kidney Study. For eGFRs
      of 60 or more, 45-59, 30-44, 15-29, and under 15 ml/min per 1.73 m(2), the mean
      serum 24,25(OH)(2)D concentrations significantly trended lower from 3.6, 3.2,
      2.6, 2.6, to 1.7 ng/ml, respectively. Non-Hispanic black race, diabetes,
      albuminuria, and lower serum bicarbonate were also independently and
      significantly associated with lower 24,25(OH)(2)D concentrations. The
      24,25(OH)(2)D concentration was more strongly correlated with that of parathyroid
      hormone than was 25(OH)D or 1,25(OH)(2)D. A 24,25(OH)(2)D concentration below the
      median was associated with increased risk of mortality in unadjusted analysis,
      but this was attenuated with adjustment for potential confounding variables.
      Thus, chronic kidney disease is a state of stagnant vitamin D metabolism
      characterized by decreases in both 1,25(OH)(2)D production and vitamin D
      catabolism.

PMID- 22648297
TI  - Viral double-stranded RNA sensors induce antiviral, pro-inflammatory, and pro
      apoptotic responses in human renal tubular epithelial cells.
AB  - Viral infection in the kidney is characterized by tubular injury induced directly
      by the virus and/or by cytotoxic lymphocytes. Previously, we found that human
      tubular epithelial cells express Toll-like receptor 3 (TLR3), melanoma
      differentiation-associated gene 5 (MDA5), and retinoic acid-inducible gene-I (RIG
      I), all sensors of double-stranded RNA (dsRNA) and potent inducers of antiviral
      activity. Here, we demonstrate increased expression of these three dsRNA sensors
      in kidney transplant biopsies during cytomegalovirus or BK virus infection. In
      primary tubular epithelial cells, dsRNA sensor activation induced the production
      of pro-inflammatory TNF-alpha and antiviral IFN-beta. Notably, dsRNA also
      enhanced the expression of pro-apoptotic proteins; however, dsRNA alone did not
      cause cell death due to the expression of anti-apoptotic proteins. The dsRNA
      sensitized tubular epithelial cells to apoptosis induced by an agonistic antibody
      against the Fas receptor (CD95), an apoptotic pathway that eliminates infected
      cells. These findings indicate that tubular epithelial cells require at least two
      signals to undergo apoptosis, which can help preserve tubular integrity even
      under inflammatory conditions. Thus, sensors of viral dsRNA promote antiviral,
      pro-inflammatory, and pro-apoptotic responses in tubular epithelial cells, which
      may orchestrate the control of viral infection in the kidney.

PMID- 22648299
TI  - The Women's Health Initiative:  an unforgettable decade.

PMID- 22648300
TI  - Hormone therapy prescribing trends in the decade after the Women's Health
      Initiative:  how patients and providers have found a way to sleep better at
      night.

PMID- 22648301
TI  - Bone density:  a surrogate for estrogen exposure or a systemic inflammatory
      disorder?

PMID- 22648302
TI  - A decade of postmenopausal hormone therapy prescribing in the United States: 
      long-term effects of the Women's Health Initiative.
AB  - OBJECTIVE: Nearly a decade ago, landmark clinical trials revealed an increase in
      the risks associated with hormone therapy in postmenopausal women, leading to
      early changes in prescribing patterns. Long-term prescribing patterns in the
      United States after these trials are unknown. The objective of this study was to
      describe changes in hormone therapy prescribing including dose, formulation,
      patient age, and prescriber specialty from 2000 to 2009. METHODS: A national
      pharmacy claims database was used to describe the annual prevalence and incidence
      rates of hormone therapy prescribing from 2000 to 2009 in women 50 years and
      older. RESULTS: Throughout the decade, a number of prescribing trends were
      observed: a continuous decline in hormone therapy overall, an initial drop in new
      therapy that stabilized after 2003, a decline in oral formulations and increase
      in vaginal formulations, a decline in standard- and high-dose and an increase in
      low-dose oral formulations, and an increase in the proportion of women who
      received hormone therapy from gynecologists. CONCLUSIONS: Overall prescribing of
      hormone therapy continued to decline during the past decade, suggesting a long
      term impact of the Women's Health Initiative findings. During this same time,
      treatment regimens shifted to favor vaginal and lower-dose oral formulations.

PMID- 22648303
TI  - Evaluation and treatment of adult concealed penis.
AB  - Concealed penis is a rare congenital disorder most commonly seen in children and
      the condition and surgical management have been well described. In contrast,
      there is a paucity of information with regards to adult concealed penis. Adult
      concealed penis may be due to trapping from skin contraction related to lichen
      sclerosis, cicatricial scars following surgical procedures, or prepubic adipose
      tissue causing poor phallic exposure. One of the greatest risk factors for
      concealed penis is obesity, and as this becomes a national pandemic, the
      incidence of adult concealed penis may increase. Therefore, a greater number of
      urologists may be faced with treating this difficult condition. This article
      reviews the etiology of adult concealed penis and describes the patient
      evaluation and various surgical approaches.

PMID- 22648305
TI  - Treatment of comorbid anxiety and depression with escitalopram: results of a post
      marketing surveillance study.
AB  - INTRODUCTION: In this 16-week post-marketing surveillance (PMS) study,
      antidepressant effects and tolerability of escitalopram was examined in 2 911
      patients with comorbid depression and anxiety. METHODS: Antidepressant effects
      were assessed using a modified version of the Montgomery-Asberg depression rating
      scale (svMADRS), the Hamilton anxiety scale (HAMA) and the hospital anxiety
      depression scale (HADS-D) and the clinical global impression scale (CGI-S, CGI
      I). RESULTS: Treatment was completed by 2 718 patients, whose severity of
      depression decreased from a mean svMADRS total score of 33.0 to 8.9. At the end
      of the study, the remission rate (svMADRS<=12) was 72.9% and the response rate
      (>=50% decrease in svMADRS score) was 83.1% (LOCF). Similarly, the severity of
      anxiety symptoms decreased from a mean HAMA total score of 28.8-8.8; the
      remission rate (HAMA<10) was 63.9% and the response rate (decrease>=50%) was
      80.2%. The most frequent adverse events were nausea (1.6%), agitation (1.1%) and
      fatigue (0.7%). DISCUSSION: Antidepressant effects and good tolerability of
      escitalopram were confirmed in everyday practice in patients with comorbid
      depression and anxiety. The high response and remission rates were within the
      range reported in previous RTC's of escitalopram vs. comparators or vs. placebo.

PMID- 22648304
TI  - Stuttering priapism: insights into pathogenesis and management.
AB  - Priapism is defined as a persistent, painful erection that continues beyond, or
      is unrelated to, sexual stimulation. It may be categorized as either ischemic
      (low/absent flow) or nonischemic (high flow). Stuttering priapism is a variant of
      the ischemic type that is characterized by repetitive, transient, painful, self
      limiting episodes of priapism. It is associated with various hematological
      disorders, including sickle cell disease and pharmacological treatments. The
      consequences of ineffective treatment of priapism are erectile dysfunction and
      impaired quality of life due to chronic pain and physical disfigurement. Many of
      the existing medical therapeutic options for treatment of stuttering priapism are
      nonmechanistic and associated with significant adverse effects. However, the
      scientific knowledge of stuttering priapism has transitioned in the past few
      years, from a condition that is poorly understood to one that has borne a burst
      of evolving molecular science. In this review, the pathophysiology of priapism is
      discussed, with particular emphasis on new molecular effectors and mechanisms.
      Novel treatment methods, as well as potential future agents, based on the
      emerging molecular evidence are discussed.

PMID- 22648306
TI  - Influences on therapist's decisions for neuroleptic treatment in schizophrenia:
      the role of characteristics of the patient and the physician.
AB  - We investigated factors influencing physicians' treatment decisions regarding 4
      antipsychotic treatment strategies for schizophrenia (conventional
      oral/conventional depot/atypical oral/atypical depot). We analysed the influence
      of the patient's compliance with medication, socio-economic status (occupational
      prestige/educational attainment), as well as the influence of gender, age and
      practice setting (psychiatric/general hospital/private practice) of the
      prescribing physician.We examined the influence of these factors by means of case
      vignettes. 4 vignettes were constructed with varying levels for compliance and
      socio-economic status. For each vignette, physicians had to choose one treatment
      strategy from the 4 alternatives. Data were collected using a survey (n=1 342) of
      physicians in Germany and analysed using a weighted least-squares regression
      model and a random-effect logit model.Compliance and status had interactive
      effects on treatment selection. Low compliance was associated with an increase in
      selections of depot medication. For high-status, noncompliant patients,
      physicians selected mainly atypical oral and atypical depot antipsychotics. Low
      status, noncompliant patients were mostly given conventional and atypical depot
      antipsychotics. Noncompliant, low-status patients received conventional depot
      antipsychotics 4 times as often as noncompliant, high-status patients. The
      physician's age and practice setting were also related to the treatment
      selection.Therapeutic decisions are influenced by patients' and the physicians'
      characteristics. There might be barriers for patients with low compliance and low
      socio-economic status that prevent them from being prescribed newer medications.
      Not all physicians seem to have the same choices of treatment options available
      to them.

PMID- 22648307
TI  - Aripiprazole use in early pregnancy: a case report.

PMID- 22648308
TI  - Synthetic approaches to a chiral 4-amino-3-hydroxy piperidine with pharmaceutical
      relevance.
AB  - Four synthetic strategies were evaluated towards the preparation of (-)-(3R,4R)-1
      benzyl-4-(benzylamino)piperidin-3-ol (1), which was constructed with control over
      the relative and absolute stereochemistry of the 4,3-amino alcohol moiety. The
      first strategy employed a novel Rh(I) catalyzed asymmetric hydrogenation, while
      two other strategies exploited the existing stereochemistry in 2-deoxy-D-ribose,
      and the fourth explored both biocatalytic and classical resolution techniques as
      a means to impart enantioenrichment to racemic intermediates en route to targeted
      structure (-)-1.

PMID- 22648310
TI  - Single molecule force spectroscopy using polyproteins.
AB  - In recent years single molecule force spectroscopy has emerged as a powerful new
      tool to explore the mechanical stability and folding pathways of individual
      proteins. This technique is used to apply a stretching force between two points
      of a protein, unfolding the protein to an extended state. By measuring the
      unfolding and folding trajectories of individual proteins, insight can be gained
      into the physical mechanisms of protein folding. In this tutorial review we
      introduce the reader to single molecule force spectroscopy using the atomic force
      microscope (AFM), and explain the two main modes of operation of the AFM for
      force spectroscopy: force-extension and force-clamp. We introduce the approach of
      using polyproteins to obtain a clear mechanical fingerprint for monitoring the
      response of proteins to an applied mechanical force. In addition, we provide an
      informative and representative review of recent research on proteins using single
      molecule force spectroscopy. We focus on areas which have made a significant
      contribution to the single molecule protein folding field and highlight emerging
      areas of research which have wider implications for the general scientific
      community.

PMID- 22648311
TI  - [Nicotine and animal models: what does the environmental enrichment paradigm tell
      us?].
AB  - The Environmental Enrichment (EE) paradigm is a housing condition which aims is
      to provide physical, cognitive and sensorial stimulation to rodents. Animals are
      housed in larger cages containing inanimate objects such as tunnels, toys and
      running wheels. The main aim of the current work is to tackle the arguments which
      suggest that EE may diminish vulnerability to developing addiction to nicotine
      and other drugs of abuse and to review recent experimental studies performed in
      relation to this subject. We discuss the major changes induced by EE at physical,
      neurobiological and behavioral levels and review the results of recent studies
      which indicate that EE promotes both neurochemical (potentiation of the increase
      in dopamine release induced by nicotine in the brain cortex) and behavioral
      changes (increased ability to discriminate the presence of reward and decreased
      impulsivity), thus supporting the hypothesis put forward. In light of these
      results, EE can be proposed as a model for the study of vulnerability to
      addiction to different drugs of abuse, including cocaine and nicotine, though
      further studies are needed in order to establish the neurobiological implications
      of the effects of exposure to enriched environments and their possible
      relationship with changes in brain reward systems.

PMID- 22648312
TI  - Advances in the development of biologics to treat drug addictions and overdose.
AB  - Drug addictions are complex disorders that require multiple approaches, including
      the use of pharmacotherapies. Currently, these therapies are based on "small"
      molecules or chemicals that penetrate the blood-brain barrier, reach the brain,
      and produce their effects on neurotransmitter systems. Unfortunately, they often
      do not have the desired efficacy or may cause undesirable side effects,
      especially at the central nervous system (CNS) level. A novel approach is the use
      of biologics to treat drug addictions. Biologics are usually complex and "large"
      molecules, which do not cross the blood-brain barrier and, thus, have no CNS
      effects. In principle, it appears that the efficacy of biologics to treat drug
      addiction is by preventing the access of the drug of abuse to the brain,
      preventing the activation of brain reward systems, and eventually producing the
      extinction of addiction. Biologic therapeutics includes immunotherapies, such as
      vaccines or antibodies, as well as enzymes. New products as well as new and more
      efficient methods of production, are offering vast opportunities to advance the
      discovery and development of biologics to treat addictions as well as drug
      overdose. These products include new vaccines with greater specificity and
      ability to produce antibodies, new methods and techniques to produce vaccines and
      antibodies, as well as new enzymes with high efficiency to metabolize cocaine.
      The purpose of the article is to provide a general overview of the development of
      biologics for the treatment of drug addictions and overdose.

PMID- 22648313
TI  - [Impulsivity and compulsivity in cocaine dependent individuals].
AB  - A recent theoretical approach describes addiction as a dynamic behavioural change
      process on the impulsivity-compulsivity axis. However, on the basis of current
      evidence, it is still difficult to establish a selective association between the
      course of addiction and individual transition along this axis. The aim of this
      study is to categorize each of the individuals in a sample of cocaine-dependent
      patients (CDI) as mainly impulsive or mainly compulsive, on the basis of their
      performance in neuropsychological inhibition and perseveration tests, and to test
      the association between the assigned category and their scores in trait
      impulsivity, and severity of cocaine addiction (measured by means of self-report
      assessment tools). A total of 42 CDI and 65 healthy control individuals (HCI)
      were assessed using the UPPS-P Scale (to explore trait impulsivity), the Stroop
      and Go/No Go (to assess response inhibition), and Revised-Strategy Application
      and Probabilistic Reversal tests (to assess response perseveration). Forty-five
      per cent of the CDIs were classified as compulsive, and this subgroup scored
      significantly higher than the impulsive group on the UPPS-P dimensions of lack of
      perseverance and lack of premeditation. A substantial proportion of CDIs can be
      classified as compulsive. No differences between compulsive and impulsive CDIs
      were found with regard to severity of exposure to cocaine; however, patients
      classified as compulsive by means of neuropsychological tasks are less
      perseverative in the pursuit of long-term objectives and more prone to make under
      meditated decisions, as shown by trait impulsivity assessment questionnaires.

PMID- 22648314
TI  - [Risk factors for relapse in drug-dependent patients after hospital
      detoxification].
AB  - This work describes the profile of patients with relapse after hospital
      detoxification at six months of outpatient follow-up. An observational and
      prospective study was carried out in patients with substance-dependence disorder
      who were in the Detoxification Unit of the Vall d'Hebron University Hospital
      (Barcelona) between June 2009 and October 2010. Demographic, clinical, diagnostic
      and therapeutic variables were assessed. The criterion for relapse was a return
      to use of the substance that had led to hospitalization, and relapse was assessed
      by means of anamnesis, breathalyzer and/or urine analysis. Study variables were
      compared between patients who relapsed and those who did not. Of the 165 patients
      included, 108 patients finished the study (75% males, age 37.7 +/- 9.5 years). A
      total of 72.2% had relapsed at the 6-month follow-up. Profile of patients who
      relapsed was: hospitalized for heroin detoxification (91.7% vs 8.3%, p = .038),
      polyconsumers (71.4% vs 32%, p = .05), high substance use in the hours prior to
      admission as a "farewell" (61.5% vs 39.5%, p = .04), patients with comorbidity
      (44.9% vs 23.3%, p = .04) and patients with affective disorders (19.5% vs 3.2%, p
      = .005). Detoxification from opiates and use in the hours prior to admission were
      associated independently with relapse at 6 months. There is a high percentage of
      relapses after hospital detoxification. Patients most likely to relapse are those
      dependent on opiates and those with compulsive use immediately prior to
      hospitalization.

PMID- 22648315
TI  - [Spanish adaptation of the "Mobile Phone Problem Use Scale" for adolescent
      population].
AB  - Problematic use of the mobile telephone is an emerging phenomenon in our society,
      and one which particularly affects the teenage population. Knowledge from
      research on the problematic use of this technology is necessary, since such use
      can give rise to a behavioural pattern with addictive characteristics. There are
      hardly any scales for measuring possible problematic use of mobile phones, and
      none at all adapted exclusively for the Spanish adolescent population. The scale
      most widely used internationally is the Mobile Phone Problem Use Scale (MPPUS).
      The aim of the present study is to adapt the MPPUS for use with Spanish
      adolescents. The Spanish version of the questionnaire was administered to a
      sample of 1132 adolescents aged 12 to 18. Reliability and factorial validity were
      comparable to those obtained in adult population, so that the measure of
      problematic mobile phone use in Spanish teenagers is one-dimensional. A
      prevalence of 14.8% of problematic users was detected.

PMID- 22648316
TI  - [Opiate dependence type II or antisocial: Cloninger's Psychobiological Model and
      its usefullness in addictions].
AB  - The aim was to analyze the relationship between Cloninger's dimensions and
      Personality Disorders (PD) (with DSM-IV criteria) in opiate dependents. The study
      was Cross-sectional. The sampling of 196 patients with opiate dependence was
      consecutive. All were receiving treatment in an inpatient detoxification unit.
      Cloninger's Temperament and Character Inventory (TCI), International Personality
      Disorders Examination (IPDE) and a Substance Use Questionnaire were used.
      Character's dimensions as Self-directness and Cooperation were related with PD
      when scored low. Opposite to Cloninger descriptions, high scores of Self
      transcendence were related with presence of PD. Related to temperamental
      dimensions, cluster A was related with low scores of Reward Dependence (RD) and
      cluster C with high scores of Harm Avoidance (HA). Otherwise, in cluster B, while
      Borderline PD had high scores of Novelty Seeking (as high HA), the Antisocial PD
      only were related to low scores of RD. RD dimension seems useful to differ from
      presence or absence of Antisocial PD, also when alcohol consumption is
      considered. Cloninger's Model of Personality is useful in drug dependents for the
      definition of the different PD, as well as for probable PD's aggregation. This
      model also helps to create subtypes in opiate dependents as the antisocial or
      type II.

PMID- 22648318
TI  - [Life skills and drug use among Mexican adolescent students].
AB  - A cross-sectional study was carried out with the purpose of validating seven life
      skills scales reported in the literature as related to drug-abuse prevention, and
      which identify differences between these skills among non-user adolescent
      students and users of alcohol, tobacco, cannabis and inhalants. The sample was
      made up of 425 adolescents, 196 (46.1%) male and 229 (53.9%) female. These
      participants were randomly selected from a private high school in the state of
      Morelos, and their mean age was 15.8 years, with a standard deviation of 1.97. To
      measure skills we used the scales validated in this survey, while patterns of
      drug use were measured with a scale based on the National Addiction Survey (2008)
      indicators. Results showed that students who did not use alcohol, tobacco,
      cannabis or inhalants scored higher in skills of empathy, future orientation and
      peer pressure resistance, compared to those who had used these substances in the
      last month. On the basis of these findings it would seem necessary to develop
      drug-abuse prevention programs for high school students based on a life skills
      training approach.

PMID- 22648317
TI  - [Mobile phone abuse or addiction. A review of the literature].
AB  - The mobile phone is a relatively new technological tool, versatile and
      accessible, and very attractive, especially for young people, but whose use
      involves a risk of abuse and addictive behavior. In recent years there has been
      increasing interest in this problem, especially in view of the fact that it
      involves an increasingly younger population. The aim of this paper is to review
      the current state of scientific knowledge about cell phone addiction/abuse. To
      this end, a search was carried out in international databases, using the
      descriptors "mobile phone", "cellular telephones", "addiction" and "abuse", and
      focusing on prevalence studies, diagnostic tests, associations with psychological
      variables and gender differences. There is a conceptual vagueness about the
      concepts of abuse and addiction in relation to mobile phones, and wide disparity
      in the adoption of diagnostic criteria; moreover, there are numerous instruments
      for the assessment of these concepts. As a result, the estimated prevalence
      ranges from 0-38%, depending on the scale used and the characteristics of the
      population studied. Surprisingly, self-attribution of cell phone addiction
      exceeds the prevalence estimated in the studies themselves. The personality trait
      most consistently associated with addiction is low self-esteem, though
      extraversion is associated with more intense use. Women with low self-esteem are
      the most vulnerable group, and the most commonly associated psychopathological
      symptom was depression. In short, while the evidence suggests a problem in
      relation to mobile phone use, the vagueness of the cell phone addiction concept
      and the poor quality of the studies make it difficult to generalize the results.
      It is necessary to define and unify criteria with a view to carrying out quality
      studies that permit appropriate comparisons.

PMID- 22648319
TI  - [Decision making in cannabis users].
AB  - Several neuropsychological studies have shown that chronic cannabis users have
      cognitive impairments, including decision-making process. Therefore, this study
      aims to evaluate the process, through the somatic marker hypothesis in a sample
      of 41 cannabis users compared with a control group of equal size, and to analyze
      the influence of age, sex, education level, age of onset and amount of daily
      consumption. In order to do that, the software "Cartas" (similar to the Iowa
      Gambling Task), was used, implementing its two versions: normal and reverse. The
      results show significant differences between cannabis users and control group in
      the normal and reverse task execution. By block analysis, the control group
      obtained higher scores in the normal task execution, however, in the reverse
      task, the differences between groups are present in the initial task execution
      but not final task execution. None of the analyzed variables (age, sex ...) are
      significantly related to task performance. These results suggest the existence of
      alterations in the decision making process of consumers cannabis, which may
      relate to the difficulty in generating somatic markers, and not for insensitivity
      punishments insensitivity.

PMID- 22648320
TI  - [Secondhand smoke exposure at home and leisure time according to the day of the
      week (working and non-working day) in Barcelona].
AB  - The objective of this study is to describe the differences in the exposure to
      secondhand smoke (SHS) at home and at leisure time according to the day of the
      week (working and non-working day) which exposure occurs in Barcelona. We carried
      out a cross-sectional study of a representative sample of adult (>16 years) non
      smokers in Barcelona before the Spanish smoking law came into effect (years 2004
      2005). We studied the prevalence of exposure to SHS at home and leisure time by
      means of a questionnaire and a biomarker (salivary cotinine). The questionnaire
      included questions on exposure to SHS on working days and nonworking days. The
      prevalence of exposure to SHS at home was 27.4% (6.8% exposed only on working
      days, 5.7% exposed only on non-working days, and 14.9% exposed on both working
      and non-working days). The prevalence of exposure to SHS at leisure time was
      61.3% (10.7% exposed only on working days, 13.6% exposed only on non-working
      days, and 37.0% exposed on both working and non-working days). The exposure to
      SHS only on non-working days at leisure time decreases with age (chi(2) of trend
      = 183.7; p<0.001) and increases with the educational level (chi(2) of trend =
      78.8; p<0.001). Participants who had reported to be exposed to SHS at home on
      working and non-working days showed higher levels of salivary cotinine
      concentration, regardless of sex, age group, and educational level. In
      conclusion, the exposure to SHS occurs mainly during leisure time. Questions on
      SHS exposure according to working and non-working days allow to characterizing
      the exposure to SHS, especially when the exposure occurs at leisure time.

PMID- 22648321
TI  - A new pathway to classification of complex hand injuries: a clinical pilot
      testing using a new method of assessment.
AB  - All existing classifications, which are based on the severity of hand injuries,
      are being referred to facets of variety of hand injuries in general. A clear
      picture of all consequences of hand injuries would be apparent, if any kind of
      injury mechanism and occurrence of an injury would be identified and academically
      captured. Predictions regarding return to the former occupation and
      rehabilitation time would be possible with further study; 102 patients with
      different hand injuries were engaged in a pilot project using a specifically
      designed assessment sheet to achieve this purpose in the framework of a
      retrospective clinical testing within 1 year. Data were summarized and
      demonstrated graphically. Each category showed a picture of prior localization of
      the injury and its morphology. All categories show specific injury patterns. The
      choice of categories reflects the mechanisms of injury emphasized in literature.
      Furthermore, the mean DASH equivalents of one category were compared to the mean
      Hand Injury Severity Scoring (HISS) scores in order to get an initial idea of
      information on the degree of severity. A first impression of the potential of
      this assessment sheet has been obtained with regard to the above. With further
      study, we could evaluate the assessment sheet and try to create a classification
      of the grade of severity as well as prognostic values like return to the former
      occupation and rehabilitation time.

PMID- 22648322
TI  - Cultural and contextual analysis of quality of life among older Nepali women.
AB  - The quality-of-life construct can be used to assess how well an individual's
      needs are met or being met by the society. However, in the dominant narratives of
      quality of life in old age, exploration of the impact of cultural differences on
      how older adults define and assess their quality of life has been limited.
      Moreover, the examination of heterogeneity within one culture and its influence
      on quality of life has been largely ignored. The present study compares the
      quality of life as defined by two samples of Nepali elderly women, those who live
      with their families and those who live in an old-age home, and presents data on
      factors associated with quality of life in the two samples. The results show that
      social and cultural norms, informed by religious principles that prescribe
      familial elder care, impact how quality of life is described by both groups of
      women.

PMID- 22648323
TI  - Gender differences in the associations of life satisfaction with family and
      social relations among the Japanese elderly.
AB  - The purpose of this study was to investigate gender differences in the
      associations of life satisfaction with family and social relations among the
      Japanese elderly. Ordered logit models were estimated to explain life
      satisfaction with a rich set of explanatory variables, using micro data of 3,277
      elderly Japanese adults (1,679 men and 1,598 women) collected from the first-wave
      sample from the Japanese Study of Aging and Retirement (JSTAR). This study found
      that men are less satisfied with life when living without their spouse; women are
      less satisfied with life when they live and/or have close relations with their
      parents-in-law; coresidence with an unmarried son is negatively associated with
      life satisfaction for both men and women; and, a larger number of friends and
      social activities enhance life satisfaction for women but not for men. Men are
      more sensitive than women to overall family relations, while the relative
      importance of social relations is higher for women. These results confirmed
      gender differences in the associations of life satisfaction with family and
      social relations in Japan-a nation characterized by a gender-asymmetric society
      and multi-generational family settings.

PMID- 22648324
TI  - What's new in antibiotics in the management of acne?
AB  - Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit with a
      multifactorial pathogenesis. Topical and oral antibiotics are a mainstay
      treatment for inflammatory acne lesions and are widely utilized for all levels of
      disease severity. Over the past forty years, a gradual increase in antibacterial
      resistant strains of Propionibacterium acnes has changed the way practitioners
      use antibiotics to manage acne. Updated recommendations call for avoiding
      antibiotic monotherapy and prescribing it in combination with benzoyl peroxide or
      retinoids. In addition to reducing the risk of developing bacterial resistance,
      antibiotics prescribed in combination formulations with benzoyl peroxide or
      retinoids are more efficacious than monotherapy, provide fast therapeutic
      results, and are associated with greater patient adherence due to the
      simplification of treatment regimens. Newer management strategies include
      limiting antibiotic use to the initial 3-6 months of treatment and then switching
      to topical retinoids for maintenance therapy.

PMID- 22648325
TI  - What genomics has taught me about melanocytic neoplasms.
AB  - Recent advances in the molecular biology of melanocytic neoplasms have enabled
      what were previously investigational tools to be used for more accurate diagnosis
      of melanocytic neoplasms. These include fluorescence in situ hybridization,
      comparative genomic hybridization, and sequencing. Correlation with conventional
      histopathology and immunohistochemistry has led to a better understanding of the
      classification of melanocytic neoplasms, as well as to the identification of new
      clinicopathologic entities. Herein are illustrated some pitfalls in the diagnosis
      of melanoma, as well as variants of Spitz's nevus that correlate with specific
      genomic aberrations such as gains of chromosome 11p and loss of the BAP-1 gene on
      chromosome 3p.

PMID- 22648326
TI  - Role of IgE in bullous pemphigoid: a review and rationale for IgE directed
      therapies.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering disorder that is
      characterized by elevated total serum IgE and both IgG and IgE class
      autoantibodies directed against the hemidesmosomal proteins BP180 and BP230. In
      BP, IgE is found at the basement membrane zone and coating mast cells in lesional
      skin. IgE binding to immune cells is mediated through its high affinity receptor,
      FcepsilonRI on the surface of mast cells, basophils and eosinophils. In BP
      lesions, IgE binding is thought to be a critical step in the activation of these
      cells. Models of the disease have demonstrated that BP IgE can replicate the
      early stages of BP lesion formation. These findings suggest that IgE inhibition
      may be a therapeutic approach for BP. Omalizumab is a humanized monoclonal
      antibody that inhibits IgE binding to FcepsilonRI and is currently FDA-approved
      for the treatment of severe allergic asthma. To date, two case reports have each
      described the efficacy of omalizumab in a patient with severe recalcitrant BP.
      These studies are the first to provide clear evidence of the contribution of IgE
      autoantibodies in the pathogenesis of human BP and suggest that omalizumab may
      provide an additional therapeutic tool for treatment.

PMID- 22648327
TI  - Intravenous immunoglobulin: recent advances in the treatment of autoimmune
      bullous diseases.
AB  - Autoimmune bullous diseases describes a heterogenous group of diseases with skin
      and mucosal involvement with varying degrees of mortality. Intravenous
      immunoglobulin (IVIg) is a specialised treatment used in the management of these
      AIBD with variable success. This paper outlines the use of IVIg in these
      diseases.

PMID- 22648329
TI  - Lasers and photodynamic therapy for the treatment of acne.
AB  - Acne vulgaris is one of the most common diseases in the United States, affecting
      40 to 50 million individuals. The condition is both a dermatologic and
      psychosocial challenge for many patients, and while topical therapy and cleansers
      continue to be the gold standard of treatment, the use of lasers and light will
      continue to play a role that will likely expand in management of acne. Modalities
      that have been explored include PDT with and without photosensitizers, KTP, PDL,
      infrared and fractional lasers. Current data evaluating these methods will be
      herewith discussed. The future application of these devices in acne therapy will
      likely include combination therapy and exploration of more precisely targeted
      chromophores.

PMID- 22648328
TI  - Rituximab for autoimmune blistering diseases: recent studies, new insights.
AB  - Rituximab, an anti-CD20 monoclonal antibody, has been successfully used off-label
      for treatment of autoimmune blistering diseases. We discuss rituximab mechanisms
      of action, host factors that may affect response to rituximab, and the efficacy
      and safety of rituximab in autoimmune blistering diseases, incorporating recent
      data on the use of rituximab in other autoimmune disease patients.

PMID- 22648330
TI  - Role of lasers in facial rejuvenation.
AB  - Different types of lasers with different mechanisms of action are available today
      for the facial rejuvenation. Sometimes it is difficult for the practitioner to
      decide which laser to use for what indication. Detailed knowledge about the
      pathogenesis of skin ageing and the mechanism of action of each available laser
      is mandatory for the appropriate diagnosis and management of patients seeking
      facial rejuvenation. This review article is addressing the mechanisms of skin
      ageing, the three main laser modalities; the non-ablative laser rejuvenation, the
      Laser resurfacing as well as the fractional photothermolysis lasers with their
      indications and modes of actions.

PMID- 22648331
TI  - The actual role of hyaluronic acid-based and calcium hydroxylapatite soft tissue
      fillers: a guide for a practicing dermatologist.
AB  - Soft tissue fillers (STFs) together with botulinum toxin have profoundly improved
      our possibilities to rejuvenate the face and other parts of human body. Among
      many types of STFs currently used for esthetic and medical indications in routine
      clinical practice dominate hyaluronic acid-based STFs and calcium
      hydroxylapatite. Collagen fillers (bovine, porcine and human) are gradually
      leaving the market replaced mostly by hyaluronic acid-based STFs. This review
      presents an overview of the physicochemical properties, mechanisms of action and
      techniques used for the correct placement of hyaluronic acid-based STFs and
      calcium hydroxylapatite and the most common esthetic indications for these
      fillers. Finally, we present the recent data on their efficacy and most common
      complications encountered.

PMID- 22648332
TI  - Epidemiology of dermatophytoses in Crete, Greece between 2004 and 2010.
AB  - AIM: The present work was undertaken in order to study the epidemiology of
      dermatophytoses in the island of Crete, Greece, over a 7-year period (2004-2010)
      and to compare the results with those reported earlier from this region and from
      other parts of the world. METHODS: A total of 3236 clinical specimens obtained
      from 2674 patients with signs of dermatomycoses were examined by direct
      micropscopy and culture. RESULTS: Overall, 392 specimens (12.1%) were proved
      mycologically positive for dermatophytes. The age of the patients ranged from 2
      to 90 years (mean age, 41 years). Onychomycosis was the predominant clinical type
      of infection, followed by tinea pedis, tinea corporis, tinea capitis, tinea
      faciei, tinea manuum and tinea cruris. Among dermatophytes, nine species were
      isolated: Trichophyton rubrum (51%), Microsporum canis (18.9%), Trichophyton
      mentagrophytes var. interdigitale (18.4%), Trichophyton mentagrophytes var.
      mentagrophytes (5.1%), Epidermophyton floccosum (3.6%), Microsporum gypseum
      (1.5%), Trichophyton violaceum (0.8%), Trichophyton verrucosum (0.5%) and
      Trichophyton tonsurans (0.2%). CONCLUSION: In our area, the most common
      dermatophyte was T. rubrum followed by M. canis. Epidemiological studies
      regarding the current prevalence of dermatophytes in a certain region are needed
      for the appropriate management of these infections and implementation of
      effective prevention and control measures.

PMID- 22648333
TI  - A preterm infant with benign neonatal hemangiomatosis and persistent patent
      ductus arteriosus: a curious comorbidity.
AB  - A female infant had been delivered prematurely at 33 weeks to a gravida 1, para
      0, 32-year-old mother following normal spontaneous vaginal delivery. Because of
      persistent patent ductus arteriosus the new born underwent surgery after 30 days.
      Four months later, when the infant arrived at our observation, approximately 13
      red, nodular hemangiomas ranging from 0.5 to 30 mm in diameter were scattered
      over the scalp, trunk, abdomen, and extremities. Laboratory and instrumental
      tests investigating visceral involvement were all negative. Our diagnosis was of
      benign neonatal hemangiomatosis. Benign neonatal hemangiomatosis is a condition
      with multiple congenital hemangiomas limited to the skin. The incidence in the
      newborn population is between 1.0% and 4% with females 4 times more affected than
      males. Solitary hemangiomas occur more frequently in premature neonates with a
      reported incidence, inversely proportional to birth weight. Although the exact
      mechanism for hemangioma development remains unknown, vascular growth factors
      seem to play a role in the pathogenesis. Proliferation most likely results from
      an imbalance between positive and negative angiogenic factors expressed by the
      hemangioma and adjacent normal tissue. Patency of the ductus arteriosus is a
      common complication of preterm birth. During the immediate postpartum period, a
      loss of vasodilatory stimuli and activation of intrinsic contractile mechanisms
      facilitates ductus lumen occlusion. The imbalance of these forces, linked to
      premature birth, interrupts the normal maturation process, leaving the immature
      ductus patent. Our case is the first one of benign neonatal hemangiomatosis and
      patency ductus arteriosus described.

PMID- 22648334
TI  - Cervicofacial actinomycosis.

PMID- 22648337
TI  - A polythiophene-derived ratiometric fluorescent sensor for highly sensitive
      determination of carbenicillin in aqueous solution.
AB  - A new ratiometric fluorescent sensor based on a quaternized quinine substituted 3
      phenylpolythiophene derivative (PTQ1) was designed and developed for facile and
      reliable detection of carbenicillin with high sensitivity and selectivity.

PMID- 22648335
TI  - Cold-adapted digestive aspartic protease of the clawed lobsters Homarus
      americanus and Homarus gammarus: biochemical characterization.
AB  - Aspartic proteinases in the gastric fluid of clawed lobsters Homarus americanus
      and Homarus gammarus were isolated to homogeneity by single-step pepstatin-A
      affinity chromatography; such enzymes have been previously identified as
      cathepsin D-like enzymes based on their deduced amino acid sequence. Here, we
      describe their biochemical characteristics; the properties of the lobster enzymes
      were compared with those of its homolog, bovine cathepsin D, and found to be
      unique in a number of ways. The lobster enzymes demonstrated hydrolytic activity
      against synthetic and natural substrates at a wider range of pH; they were more
      temperature-sensitive, showed no changes in the K(M) value at 4 degrees C, 10
      degrees C, and 25 degrees C, and had 20-fold higher k(cat)/K(M) values than
      bovine enzyme. The bovine enzyme was temperature-dependent. We propose that both
      properties arose from an increase in molecular flexibility required to compensate
      for the reduction of reaction rates at low habitat temperatures. This is
      supported by the fast denaturation rates induced by temperature.

PMID- 22648338
TI  - Reducing sexual risk behavior among high-risk couples in Northern India.
AB  - BACKGROUND: With a population of 1.1 billion, India is considered to be a country
      in which effective prevention interventions could contain the development of a
      human immunodeficiency virus (HIV) epidemic. Heterosexual transmission accounts
      for 85 % of the extant HIV infections. PURPOSE: This study sought to assess the
      feasibility of conducting a group, culturally tailored behavioral intervention
      and its impact on sexual barrier use, self-efficacy, knowledge, conflict
      resolution, and coping among high-risk heterosexual couples in Northern India.
      METHOD: This pilot study was conducted at the Postgraduate Institute of Medical
      Education and Research (PGIMER), Chandigarh, India from February 2008 to January
      2009. Thirty sexually active high-risk couples were drawn from a convenience
      sample of PGIMER patients attending infectious disease and family planning
      clinics. Couples participated in 1 month of three weekly gender-concordant
      behavioral intervention groups and were individually administered assessments
      preintervention and post-intervention. The intervention was tailored to the
      Northern Indian context and addressed sexual barrier use, human immunodeficiency
      virus (HIV)/sexually transmitted infection transmission, and cognitive behavioral
      skill building focusing on sexual negotiation and communication. RESULTS: The
      participants had a mean age of 32 years (men) and 29 years (women), and the
      majority had at least 10 years of education. At baseline, the majority reported
      inconsistent condom use (<100 % of the time; 64 % of women, 59 % of men). Post
      intervention, nearly all participants reported consistent condom use (100 % of
      the time; 100 % of men, 97 % of women). Participants also reported decreased
      verbal aggression, increased self-efficacy, and increased HIV-related knowledge,
      and women increased their use of positive coping tactics. CONCLUSIONS: The
      results highlight the potential to successfully utilize a group intervention to
      discuss sensitive issues such as sexual risk behavior among both men and women.
      Strategies to improve condom use and communication without increasing intimate
      partner violence in high-risk couples may be an important adjunct to preventing
      the development of a generalized epidemic in India.

PMID- 22648340
TI  - Increased carbon monoxide clearance during exercise in humans.
AB  - PURPOSE: Hyperventilation increases the clearance of carbon monoxide (CO) from
      blood; thus, we hypothesized that CO elimination would be enhanced with exercise.
      Accordingly, this study examined the effect of exercise on the half-life of
      carboxyhemolobin elimination. METHODS: Six healthy subjects (three males and
      three females) with mean +/- SD ages of 23 +/- 4 yr were exposed to CO sufficient
      to raise blood carboxyhemolobin concentration to 10-14% on five separate days.
      The half-life for CO elimination was measured breathing room air at rest and
      during exercise at three intensities. RESULTS: Comparisons showed that the half
      life decreased with exercise from that during rest in all subjects. The half-life
      was also measured during 100% oxygen breathing at the lowest exercise intensity
      of 63 +/- 15 W and found to be the least of all measured (23 +/- 4 min).
      CONCLUSIONS: 1) Exercise increased isocapnic ventilation, thereby decreasing the
      half-life of CO elimination. 2) The half-life of CO elimination represents a
      hyperbolic function of ventilation [y = y0 + (a / x)], and so increasing
      ventilation by exercise reaches a point of diminishing returns. 3) Breathing 100%
      oxygen during mild exercise is as effective in eliminating CO as treatment with
      hyperbaric oxygen. 4) Moderate exercise under room air conditions is as effective
      in eliminating CO as breathing oxygen at rest. Thus, the combination of mild
      exercise, hyperventilation, and normobaric hyperoxia (100% oxygen inhalation) may
      be considered the "triple therapy" for CO elimination in some patients.

PMID- 22648339
TI  - Comparison of the efficacy of different-sized Amplatzer duct occluders (I, II,
      and II AS) in children weighing less than 10 kg.
AB  - The transcatheter closure of patent ductus arteriosus (PDA) may cause more
      complications in small children. Amplatzer (St. Jude Medical, Plymouth, MN) has
      produces three types of devices for ductal occlusion: the Amplatzer duct occluder
      I (ADO I) and II (ADO II) and the recently introduced ADO II additional sizes
      (ADO II AS). We performed this study to determine the efficacy and complication
      rates in children who weigh <10 kg for the three types of devices used in our
      clinic. Between February 2007 and March 2012, 77 patients weighing <10 kg had
      their PDAs occluded with ADOs. The mean age of the patients was 0.76 +/- 0.44
      years (range 17 days-2 years), and their mean weight was 6.73 +/- 2.05 (range 1.2
      9.9) kg. In total, 54 girls (70.1 %) and 23 boys (29.9 %) with a mean pulmonary
      ductus diameter of 2.55 +/- 1.0 (1.08-5.94) mm were included in the study. The
      ADO I was used in 26 patients (33.8 %); the ADO II was used in 43 patients (55.8
      %); and the ADO II AS was used in 8 patients (10.4 %). The mean ages of patients
      with the ADO I, ADO II, and ADO II AS were 1.07 +/- 0.48, 0.66 +/- 0.31, and 0.28
      +/- 0.17 years (p < 0.05), respectively. Their mean weights were 7.86 +/- 1.45,
      6.50 +/- 1.85, and 4.36 +/- 2.49 kg (p < 0.05), respectively. Their mean
      narrowest ductal diameters were 3.11 +/- 0.96, 2.25 +/- 1.06, and 2.33 +/- 1.01
      mm (p < 0.05), respectively. The use of the ADO II and ADO II AS was found to be
      more common in type C defects. One patient with the ADO I and 5 patients with the
      ADO II (7.8 %) developed varying degrees of left pulmonary artery stenosis or
      iatrogenic aortic coarctation. In 1 patient, the ADO II AS was replaced with the
      ADO II due to a significant residual shunt observed during the procedure. Each of
      the ADOs has its own advantages and disadvantages. Although the ADO I is
      convenient for medium- and large-sized defects, the ADO II and ADO II AS can be
      used both anterogradely and retrogradely. The ADO II AS is safe and efficient to
      use in small infants.

PMID- 22648341
TI  - Flow-mediated dilation is acutely improved after high-intensity interval
      exercise.
AB  - PURPOSE: Cardiovascular disease is characterized by decreased endothelial
      function. Chronic exercise training improves endothelial function in individuals
      with cardiovascular diseases; however, the acute endothelial responses to a
      single bout of exercise are not consistent in the literature. This study
      investigated whether a single bout of moderate-intensity endurance exercise (END)
      and low-volume high-intensity interval exercise (HIT) on a cycle ergometer
      resulted in similar acute changes in endothelial function. METHODS: Ten
      individuals (66 +/- 11 yr) with coronary artery disease (CAD) participated in two
      exercise sessions (END and HIT). Endothelial-dependent function was assessed
      using brachial artery flow-mediated dilation (FMD) preexercise and 60 min
      postexercise. Brachial artery diameters and velocities were determined using
      Doppler ultrasound before and after a 5 min ischemic period at all time points.
      Endothelial-independent function was assessed using a 0.4-mg sublingual dose of
      nitroglycerin. RESULTS: The total work performed was higher in END (166 +/- 52
      kJ) compared with HIT (93 +/- 28 kJ) exercise (P < 0.001). Endothelial-dependent
      function improved (P = 0.01) after END (absolute FMD preexercise, 0.24 +/- 0.18
      mm; postexercise, 0.31 +/- 0.24 mm) and HIT (absolute FMD preexercise, 0.25 +/-
      0.13 mm; postexercise, 0.29 +/- 0.13 mm), with no differences between exercise
      conditions. A time effect for FMD normalized to the shear rate area under the
      curve was also observed (P = 0.02) after END (preexercise, 0.005 +/- 0.004;
      postexercise, 0.010 +/- 0.011) and HIT (preexercise, 0.005 +/- 0.004;
      postexercise, 0.009 +/- 0.011). Endothelial-independent function responses were
      unchanged after END and HIT (P > 0.05). CONCLUSIONS: HIT and END resulted in
      similar acute increases in brachial artery endothelial-dependent function in a
      population with dysfunction at rest, despite the difference in exercise
      intensities.

PMID- 22648342
TI  - Moderate-intensity running causes intervertebral disc compression in young
      adults.
AB  - BACKGROUND: Decreased intervertebral disc (IVD) volume can result in diminished
      load-carrying capacity of the spinal region. Although moderate-intensity running
      is generally advocated for apparently healthy adults, running causes a loss in
      stature that is thought to reflect IVD compression. The aim of this investigation
      was to use magnetic resonance imaging (MRI) to quantify the influence of moderate
      intensity treadmill running on IVD height and volume in the thoracic and lumbar
      regions of the vertebral column. METHODS: A clinic-based repeated-measures design
      was used in eight healthy young asymptomatic adults. After preliminary
      measurements and familiarization (day 1), participants reported to the clinic on
      two further occasions. MRI scans and stature measurements were completed at
      baseline (day 2), preexercise (day 3), and after 30 min of moderate-intensity
      treadmill running (postexercise, day 3). Mean height and volume were derived for
      all thoracic and lumbar IVDs from digitized MRIs, and stature was determined with
      a stadiometer. RESULTS: Moderate-intensity running resulted in 6.3% +/- 0.9%
      reduction in mean IVD height and 6.9% +/- 1.0% reduction in calculated IVD
      volume. The day-to-day variation in mean IVD height and volume were 0.6% +/- 0.6%
      and 0.4% +/- 0.6%, respectively. CONCLUSIONS: This is the first study to quantify
      the influence of moderate-intensity running on IVD height and volume. Changes in
      IVD height and volume were observed throughout the thoracic and lumbar vertebral
      regions. These findings suggest that future studies evaluating the influence of
      various loading activities and recovery techniques on IVD structure should
      consider thoracic as well as lumbar regions of the spine.

PMID- 22648343
TI  - Validity of two wearable monitors to estimate breaks from sedentary time.
AB  - Investigations using wearable monitors have begun to examine how sedentary time
      behaviors influence health. PURPOSE: The objective of this study is to
      demonstrate the use of a measure of sedentary behavior and to validate the
      activPAL (PAL Technologies Ltd., Glasgow, Scotland) and ActiGraph GT3X
      (Actigraph, Pensacola, FL) for estimating measures of sedentary behavior:
      absolute number of breaks and break rate. METHODS: Thirteen participants
      completed two 10-h conditions. During the baseline condition, participants
      performed normal daily activity, and during the treatment condition, participants
      were asked to reduce and break up their sedentary time. In each condition,
      participants wore two ActiGraph GT3X monitors and one activPAL. The ActiGraph was
      tested using the low-frequency extension filter (AG-LFE) and the normal filter
      (AG-Norm). For both ActiGraph monitors, two count cut points to estimate
      sedentary time were examined: 100 and 150 counts per minute. Direct observation
      served as the criterion measure of total sedentary time, absolute number of
      breaks from sedentary time, and break rate (number of breaks per sedentary hour
      (brk.sed-h)). RESULTS: Break rate was the only metric sensitive to changes in
      behavior between baseline (5.1 [3.3-6.8] brk.sed-h) and treatment conditions (7.3
      [4.7-9.8] brk.sed-h) (mean (95% confidence interval)). The activPAL produced
      valid estimates of all sedentary behavior measures and was sensitive to changes
      in break rate between conditions (baseline, 5.1 [2.8-7.1] brk.sed-h; treatment,
      8.0 [5.8-10.2] brk.sed-h). In general, the AG-LFE and AG-Norm were not accurate
      in estimating break rate or the absolute number of breaks and were not sensitive
      to changes between conditions. CONCLUSION: This study demonstrates the use of
      expressing breaks from sedentary time as a rate per sedentary hour, a metric
      specifically relevant to free-living behavior, and provides further evidence that
      the activPAL is a valid tool to measure components of sedentary behavior in free
      living environments.

PMID- 22648344
TI  - Analysis of pacing strategy selection in elite 400-m freestyle swimming.
AB  - INTRODUCTION: Pacing strategy selection can exert a significant influence on
      performance in events where time to completion is the measure of success.
      However, few studies exist examining pacing in elite sport, with even less
      examining pacing in swimming. PURPOSE: The objective of this study is to identify
      which type of pacing profiles are most prominently used in elite 400-m freestyle
      swimming. METHODS: Two hundred sixty-four swims from elite national and
      international competitions were analyzed in high-frequency pacing capture for
      mean speed (every 6% of the race). Each swim was subsequently categorized into
      one of six different pacing strategies through a computer algorithm and then
      performance analyzed in relation to completion time to the current world record,
      sex, and swimming suit used. RESULTS: Fast-start-even and parabolic pacing
      profiles were the most frequently used, irrespective of sex or swimming suit worn
      (120 and 89 swims, respectively). Although these strategies yielded closer
      performance times to the world record (96.08% +/- 2.12% and 96.04% +/- 2.2%,
      respectively) than other strategies, this difference was nonsignificant (F2,228 =
      1.00, P > 0.05). CONCLUSIONS: This is the first study using a large sample size
      in elite freestyle swimming to demonstrate that a fast-start-even and parabolic
      pacing strategy are most frequently used in elite competition. The performance
      benefits that these strategies may yield should be considered by coaches and
      athletes, with possible integration of pacing training before competition.

PMID- 22648345
TI  - Use of carbonised beet pulp carbon for removal of Remazol Turquoise Blue-G 133
      from aqueous solution.
AB  - Carbonised beet pulp (BPC) produced from agricultural solid waste by-product in
      sugar industry was used as adsorbent for the removal of Remazol Turquoise Blue-G
      133 (RTB-G 133) dye in this study. The kinetics and equilibrium of sorption
      process were investigated with respect to pH, temperature and initial dye
      concentration. Adsorption studies with real textile wastewater were also
      performed. The results showed that adsorption was a strongly pH-dependent
      process, and optimum pH was determined as 1.0. The maximum dye adsorption
      capacity was obtained as 47.0 mg g(-1)at the temperature of 25  degrees C at this
      pH value. The Freundlich and Langmuir adsorption models were used for describing
      the adsorption equilibrium data of the dye, and isotherm constants were evaluated
      depending on sorption temperature. Equilibrium data of RTB-G 133 sorption fitted
      very well to the Freundlich isotherm. Mass transfer and kinetic models were
      applied to the experimental data to examine the mechanisms of adsorption and
      potential rate-controlling steps. It was found that both external mass transfer
      and intra-particle diffusion played an important role in the adsorption
      mechanisms of dye and adsorption kinetics followed the pseudo second-order type
      kinetic model. The thermodynamic analysis indicated that the sorption process was
      exothermic and spontaneous in nature.

PMID- 22648346
TI  - Variations of surface O3 in August at a rural site near Shanghai: influences from
      the West Pacific subtropical high and anthropogenic emissions.
AB  - Large day-to-day variability in O(3) and CO was observed at Chongming, a remote
      rural site east of Shanghai, in August 2010. High ozone periods (HOPs) that
      typically lasted for 3-5 days with daily maximum ozone exceeding 102 ppb were
      intermittent with low ozone periods (LOPs) with daily maximum ozone less than 20
      ppb. The correlation analysis of ozone with meteorological factors suggests that
      the large variations of surface ozone are driven by meteorological conditions
      correlated with the changes in the location and intensity of the west Pacific
      subtropical high (WPSH) associated with the East Asian summer monsoon (EASM).
      When the center of WPSH with weaker intensity is to the southeast of Chongming
      site, the mixing ratios and variability of surface ozone are higher. When the
      center of WPSH with stronger intensity is to the northeast of Chongming site, the
      mixing ratios and variability of surface ozone are lower. Sensitivity simulations
      using the GEOS-Chem chemical transport model indicate that meteorological
      condition associated with WPSH is the primary factor controlling surface ozone at
      Chongming in August, while local anthropogenic emissions make significant
      contributions to surface ozone concentrations only during HOP.

PMID- 22648347
TI  - Seasonal and air mass trajectory effects on dissolved organic matter of bulk
      deposition at a coastal town in south-western Europe.
AB  - Rainwater contains a complex mixture of organic compounds which may influence
      climate, terrestrial and maritime ecosystems and thus human health. In this work,
      the characteristics of DOM of bulk deposition at a coastal town on the southwest
      of Europe were assessed by UV-visible and three-dimensional excitation-emission
      matrix fluorescence spectroscopies and by dissolved organic carbon (DOC) content.
      The seasonal and air mass trajectory effects on dissolved organic matter (DOM) of
      bulk deposition were evaluated. The absorbance at 250 nm (UV(250 nm)) and
      integrated fluorescence showed to be positively correlated with each other, and
      they were also positively correlated to the DOC in bulk deposition, which suggest
      that a constant fraction of DOM is likely to fluoresce. There was more
      chromophoric dissolved organic matter (CDOM) present in summer and autumn seasons
      than in winter and spring. Bulk deposition associated with terrestrial air masses
      contained a higher CDOM content than bulk deposition related to marine air
      masses, thus highlighting the contribution of terrestrial/anthropogenic sources.

PMID- 22648348
TI  - Quantification of bisphenol A, 353-nonylphenol and their chlorinated derivatives
      in drinking water treatment plants.
AB  - Bisphenol A (BPA) and nonylphenols (NP) are of major concern to public health due
      to their high potential for human exposure and to their demonstrated toxicity
      (endocrine disruptor effect). A limited number of studies have shown that BPA and
      NP are present in drinking water. The chlorinated derivatives that may be formed
      during the chlorination step in drinking water treatment plants (DWTP) exhibit a
      higher level of estrogenic activity than their parent compounds. The aim of this
      study was to investigate BPA, 353NP, and their chlorinated derivative
      concentrations using an accurate and reproducible method of quantification. This
      method was applied to both surface and treated water samples from eight French
      DWTPs producing from surface water. Solid-phase extraction followed by liquid
      chromatography-tandem mass spectrometry was developed in order to quantify target
      compounds from water samples. The limits of detection ranged from 0.3 to 2.3 ng/L
      for BPA and chlorinated BPA and from 1.4 to 63.0 ng/L for 353NP and chlorinated
      353NP. BPA and 353NP were found in most analyzed water samples, at a level
      ranging from 2.0 to 29.7 ng/L and from 0 to 124.9 ng/L, respectively. In most of
      DWTPs a decrease of BPA and 353NP was observed between surface water and treated
      water (36.6 to 78.9 % and 2.2 to 100.0 % for BPA and 353NP, respectively).
      Neither chlorinated BPA nor chlorinated 353NP was detected. Even though BPA and
      353NP have been largely removed in the DWTPs studied, they have not been
      completely eliminated, and drinking water may consequently remain a source of
      human exposure.

PMID- 22648349
TI  - Phytotoxicity of composted herbal pharmaceutical industry wastes.
AB  - This work demonstrates the phytotoxicity screening of composted herbal
      pharmaceutical industry waste (HPIW) using seed bioassay method. The composted
      industrial waste should be tested at lab scale prior to recommendation for land
      application. HPIW was mixed with soil to produce four treatments: T(1) (1:1),
      T(2) (1:2), T(3) (1:3), and T(4) (1:0) for toxicity screening using Pisum sativum
      seeds. After 72 h relative seed germination (RSG), relative root growth (RRG) and
      germination index (GI) were recorded. Seedlings were observed for further plant
      growth and tissue biochemistry (chlorophyll, soluble sugar, starch, carotenoid,
      and protein) estimation. RSG, RRG, and GI values were better in T(1) and T(2)
      than others. GI was in the ranges of 36.62 % (T(4)) to 170.38 % (T(2)). The
      seedling growth and biochemical parameters were better in seedling obtained from
      potting media containing low proportion of HPIW (i.e., T(1) and T(2)). Results
      clearly suggested that composted HPIW may be utilized effectively for crop
      production after dilution under sustainable farming system program.

PMID- 22648350
TI  - Source apportionment of sediment-associated aliphatic hydrocarbon in a
      eutrophicated shallow lake, China.
AB  - Chaohu Lake, one of the most eutrophicated lakes in China, has been suffering
      from long-term outside pollution, urban sewage, river outflows, and agricultural
      runoff which expectedly have been the main contributors of hydrocarbons. However,
      the contributions from these various sources have not been specified. The present
      study is aimed at identifying the potential sources of hydrocarbons in surface
      sediment around the whole lake and assessing the relative contributions using
      principal components analysis-multiple linear regression (PCA-MLR). Sixty-one
      surface sediments covering the whole Chaohu Lake and three main estuaries of
      inflowing rivers were collected, dried, extracted, and analyzed for 27 normal
      alkanes (n-alkanes, from C(12) to C(38), defined Sigma(27)AH) and unresolved
      complex mixture (UCM) by GC/MS. Diagnostic ratios and PCA-MLR were utilized to
      apportion their sources. The concentrations of Sigma(27)AH and UCM ranged from
      434 to 3,870 ng/g and 11.9 to 325 MUg/g dry weight, respectively, for all
      samples. The concentrations of Sigma(27)AH in western region and estuary of
      Nanfei River were slightly higher but without statistical significance than those
      from eastern region and estuaries of Yuxi River and Hangbu River. The
      concentration of UCM from western region was significantly higher than that
      obtained from eastern region. These results reflect the importance of input of
      urban runoff by Nanfei River and serious eutrophication in western region.
      Aliphatic hydrocarbons in Chaohu Lake were mainly derived from high plant wax
      with mixed sources of phytoplankton and petroleum. Weak microbial decomposition
      of n-alkanes would be expected to occur from the low ratios of isoprenoid
      hydrocarbons pristine (pri) and phytane (phy) to n-C(17) and n-C(18),
      respectively. Higher plant, fossil combustion, petroleum residue, and
      phytoplankton were proposed as the main origines of aliphatic hydrocarbons by PCA
      while the contributions of individual n-alkane homologues, pri and phy from the
      identified sources (31 % from higher plant, 30 % from fossil combustion, 26 %
      from petroleum, and 19 % from phytoplankton) were well predicted using MLR. The
      distribution profile and corresponding diagnostic ratios of normal alkanes show
      the promising potential as a useful proxy for estimating the source and loading
      of pollutants in Chaohu Lake.

PMID- 22648351
TI  - Response surface optimization of a dynamic dye adsorption process: a case study
      of crystal violet adsorption onto NaOH-modified rice husk.
AB  - The adsorption of crystal violet from aqueous solution by NaOH-modified rice husk
      was investigated in a laboratory-scale fixed-bed column. A two-level three factor
      (2(3)) full factorial central composite design with the help of Design Expert
      Version 7.1.6 (Stat Ease, USA) was used for optimisation of the dynamic dye
      adsorption process and evaluation of interaction effects of different operating
      parameters: initial dye concentration (100-200 mg L(-1)), flow rate (10-30 mL
      min(-1)) and bed height (5-25 cm). A correlation coefficient (R (2)) value of
      0.999, model F value of 1,936.59 and its low p value (<0.0001) along with lower
      value of coefficient of variation (1.38 %) indicated the fitness of the response
      surface quadratic model developed during the present study. Numerical
      optimisation applying desirability function was used to identify the optimum
      conditions for a targeted breakthrough time of 12 h. The optimum conditions were
      found to be initial solution pH=8.00, initial dye concentration=100 mg L(-1),
      flow rate=22.88 mL min(-1) and bed height=18.75 cm. A confirmatory experiment was
      performed to evaluate the accuracy of the optimised procedure. Under the
      optimised conditions, breakthrough appeared after 12.2 h and the column
      efficiency was determined as 99 %. The Thomas model showed excellent fit to the
      dynamic dye adsorption data obtained from the confirmatory experiment. Thereby,
      it was concluded that the current investigation gives valuable insights for
      designing and establishing a continuous wastewater treatment plant.

PMID- 22648352
TI  - New issues in heart transplantation for heart failure.
AB  - OPINION STATEMENT: Heart transplantation is the preferred therapy for patients
      with end-stage heart failure with refractory symptoms despite optimal medical and
      device therapy. The major impediment to survival is rejection and infection in
      the short term and cardiac allograft vasculopathy and malignancy in the long
      term. Current therapies are focused on the prevention and treatment of rejection
      and limiting the long-term problems of cardiac allograft vasculopathy and
      malignancy. Advances in monitoring assays now allow better assessment of
      rejection and the level of immune response. This will allow clinicians, in the
      future, to tailor current therapies to the needs of individual heart transplant
      recipients to maximize benefit and minimize toxicity.

PMID- 22648355
TI  - The cycle of development, publication, and implementation of clinical practice
      guidelines for CKD.
AB  - Implementation of clinical practice guidelines (CPGs) leads to better outcomes.
      The first K/DOQI guideline for chronic kidney disease (CKD) recommended the use
      of estimated glomerular filtration rate (eGFR) to assess kidney function,
      minimizing 24-h urine collections for the measurement of creatinine clearance.
      Kagoma et al. demonstrate that automatic reporting of eGFR with clinical decision
      support was required for implementation of this recommendation. The second cycle
      of development, publication, and implementation of CPGs for CKD is under way.

PMID- 22648356
TI  - Double-edged sword: a p53 regulator mediates both harmful and beneficial effects
      in experimental acute kidney injury.
AB  - Acute kidney injury triggers activation of innate immune responses and of
      proapoptotic programs such as the p53 pathway. Mulay et al. examine the effects
      of blocking murine double minute-2 (mdm2), a negative regulator of p53, using a
      novel chemotherapeutic agent, nutlin-3a, in mouse ischemia-reperfusion injury.
      Their results indicate that mdm2 promotes renal regeneration by limiting p53
      mediated apoptosis but also enhances early inflammation by facilitating DNA
      binding of nuclear factor-kappaB independently of p53.

PMID- 22648357
TI  - Does IgA antibody against beta2 glycoprotein I increase cardiovascular risk in
      hemodialysis patients?
AB  - Cardiovascular disease is the most common cause of mortality in patients with
      chronic kidney disease on hemodialysis. In addition to a high prevalence of
      traditional cardiovascular risk factors, other specific factors, including uremia
      and chronic inflammation, seem to contribute to the excess cardiovascular
      mortality. The findings of Serrano et al. point to a link between IgA antibodies
      against beta2 glycoprotein I and cardiovascular events in renal dialysis
      patients.

PMID- 22648358
TI  - Biosimilar recombinant human erythropoietin induces the production of
      neutralizing antibodies.

PMID- 22648361
TI  - Hemodialysis vs. peritoneal dialysis in chronic heart failure: getting to the
      heart of the matter.

PMID- 22648363
TI  - Red blood cell life span and 'erythropoietin resistance'.

PMID- 22648365
TI  - On uncertain etiologies of proteinuric-chronic kidney disease in rural Sri Lanka.

PMID- 22648367
TI  - The more or less 'pristine' renal allograft biopsy.

PMID- 22648371
TI  - Reddish-orange discoloration of urine due to uric acid crystalluria after
      recurrent seizures.

PMID- 22648372
TI  - Synergy between Glomus fasciculatum and a beneficial Pseudomonas in reducing root
      diseases and improving yield and forskolin content in Coleus forskohlii Briq.
      under organic field conditions.
AB  - Root rot and wilt, caused by a complex involving Fusarium chlamydosporum (Frag.
      and Cif.) and Ralstonia solanacearum (Smith), are serious diseases affecting the
      cultivation of Coleus forskohlii, a crop with economic potential as a source of
      the medicinal compound forskolin. The present 2-year field experiments were
      conducted with two bioinoculants (a native Pseudomonas monteilii strain and the
      exotic arbuscular mycorrhizal (AM) fungus Glomus fasciculatum) alone and in
      combination under organic field conditions in order to evaluate their potential
      in controlling root rot and wilt. Combined inoculation of P. monteilii with G.
      fasciculatum significantly increased plant height, plant spread, and number of
      branches; reduced disease incidence; and increased tuber dry mass of C.
      forskohlii, compared to vermicompost controls not receiving any bioinoculants.
      Increase in tuber yields was accompanied by an increase in plant N, P, and K
      uptake. Co-inoculation of P. monteilii with G. fasciculatum significantly
      improved the percent AM root colonization and spore numbers retrieved from soil.
      This suggests P. monteilii to be a mycorrhiza helper bacterium which could be
      useful in organic agriculture. The forskolin content of tubers was significantly
      increased by the inoculation treatments of P. monteilii, G. fasciculatum, and P.
      monteilii + G. fasciculatum.

PMID- 22648376
TI  - Graphene and its derivatives: switching ON and OFF.
AB  - As the thinnest material ever known in the universe, graphene has been attracting
      tremendous amount of attention in both materials science and condensed-matter
      physics since its successful isolation a few years ago. This one-atom-thick two
      dimensional pseudo-infinite nano-crystal consists of sp(2)-hybridized aromatic
      carbon atoms covalently packed into a continuous hexagonal lattice. Graphene
      exhibits a range of unique properties, viz., high three-dimensional aspect ratio
      and large specific surface area, superior mechanical stiffness and flexibility,
      remarkable optical transmittance, extraordinary thermal response and excellent
      electronic transport properties, promising its applications in the next
      generation electronics. To switch graphene and its derivatives between ON and OFF
      states in nanoelectronic memory devices, various techniques have been developed
      to manipulate the carbon atomic sheets via introducing the valence-conduction
      bandgap and to enhance their processability. In this article, we review the
      utilization of electrically, thermally and chemically modified graphene and its
      polymer-functionalized derivatives for switching and information storage
      applications. The challenges posed on the development of novel graphene materials
      and further enhancements of the device switching performance have also been
      discussed.

PMID- 22648373
TI  - Interplay of genetic risk factors (CHRNA5-CHRNA3-CHRNB4) and cessation treatments
      in smoking cessation success.
AB  - OBJECTIVE: Smoking is highly intractable, and the genetic influences on cessation
      are unclear. Identifying the genetic factors affecting smoking cessation could
      elucidate the nature of tobacco dependence, enhance risk assessment, and support
      development of treatment algorithms. This study tested whether variants in the
      nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 predict age at smoking
      cessation and relapse after an attempt to quit smoking. METHOD: In a community
      based, crosssectional study (N=5,216) and a randomized comparative effectiveness
      smoking cessation trial (N=1,073), the authors used Cox proportional hazard
      models and logistic regression to model the relationships of smoking cessation
      (self-reported quit age in the community study and point-prevalence abstinence at
      the end of treatment in the clinical trial) to three common haplotypes in the
      CHRNA5-CHRNA3-CHRNB4 region defined by rs16969968 and rs680244. RESULTS: The
      genetic variants in the CHRNA5-CHRNA3-CHRNB4 region that predict nicotine
      dependence also predicted a later age at smoking cessation in the community
      sample. In the smoking cessation trial, haplotype predicted abstinence at end of
      treatment in individuals receiving placebo but not among individuals receiving
      active medication. Haplotype interacted with treatment in affecting cessation
      success. CONCLUSIONS: Smokers with the high-risk haplotype were three times as
      likely to respond to pharmacologic cessation treatments as were smokers with the
      low-risk haplotype. The high-risk haplotype increased the risk of cessation
      failure, and this increased risk was ameliorated by cessation pharmacotherapy. By
      identifying a high-risk genetic group with heightened response to smoking
      cessation pharmacotherapy, this work may support the development of personalized
      cessation treatments.

PMID- 22648377
TI  - The protective effect of 3-deoxysappanchalcone on in vitro influenza virus
      induced apoptosis and inflammation.
AB  - Influenza virus is one of the most important causes of acute respiratory disease.
      Viral infection and viral replication activate multiple cell signalling pathways.
      Apoptosis of infected cells and immune response against viral replication, which
      are generally considered to be protective mechanisms, are also probably mediated
      by viruses, which lead to severe health problems. We previously reported that 3
      deoxysappanchalcone (3-DSC), a compound that is isolated from Caesalpinia sappan,
      exhibited in vitro anti-influenza activity. In the present study, we further
      identified that 3-DSC inhibited viral genomic replication and transcription only
      at a relatively high concentration. We then evaluated the effect of 3-DSC on the
      regulation of virus-induced cellular apoptosis. 3-DSC ameliorated virus-induced
      DNA fragmentation in a concentration-dependent manner, which tends to be a
      consequence of its inhibition of upstream caspase activation. 3-DSC also
      protected host cells against influenza-induced inflammation by suppressing CCL5
      and CXCL10 secretions in endothelial cells and reducing the production of IL-6
      and IL-1beta in monocytes/macrophages. In conclusion, our results demonstrate
      that anti-influenza virus mechanisms of 3-DSC involved anti-apoptosis and anti
      inflammation activities in vitro. Moreover, 3-DSC could be a promising drug
      candidate for influenza treatment.

PMID- 22648375
TI  - The NOX toolbox: validating the role of NADPH oxidases in physiology and disease.
AB  - Reactive oxygen species (ROS) are cellular signals but also disease triggers;
      their relative excess (oxidative stress) or shortage (reductive stress) compared
      to reducing equivalents are potentially deleterious. This may explain why
      antioxidants fail to combat diseases that correlate with oxidative stress.
      Instead, targeting of disease-relevant enzymatic ROS sources that leaves
      physiological ROS signaling unaffected may be more beneficial. NADPH oxidases are
      the only known enzyme family with the sole function to produce ROS. Of the
      catalytic NADPH oxidase subunits (NOX), NOX4 is the most widely distributed
      isoform. We provide here a critical review of the currently available
      experimental tools to assess the role of NOX and especially NOX4, i.e. knock-out
      mice, siRNAs, antibodies, and pharmacological inhibitors. We then focus on the
      characterization of the small molecule NADPH oxidase inhibitor, VAS2870, in vitro
      and in vivo, its specificity, selectivity, and possible mechanism of action.
      Finally, we discuss the validation of NOX4 as a potential therapeutic target for
      indications including stroke, heart failure, and fibrosis.

PMID- 22648378
TI  - Sesquiterpene lactones from Inula hupehensis inhibit nitric oxide production in
      RAW264.7 macrophages.
AB  - Phytochemical investigation of the aerial parts of Inula hupehensis Ling. led to
      the isolation and identification of 27 sesquiterpene lactones (1-27), including
      three new eudesmanolides (3-5), three new germacranolides (9-11), one new
      xanthanolide (16), two new carabrone derivatives (25-26), and 18 known
      sesquiterpene lactones. The structures were elucidated by extensive spectroscopic
      methods and comparison to previously reported spectroscopic data. All compounds
      were evaluated for their inhibitory effects against LPS-induced nitric oxide
      production in RAW264.7 macrophages, and compound 5 showed the strongest activity
      with the IC50 value of 3.2 +/- 0.4 uM.

PMID- 22648379
TI  - Decreased thalamo-cortical connectivity by alteration of neural information flow
      in theta oscillation in depression-model rats.
AB  - Alterations in oscillatory brain activity are strongly correlated with cognitive
      performance in various physiological rhythms. The present study investigated
      whether the directionality of neural information flow (NIF) could be used to
      characterize the synaptic plasticity in thalamocortical (TC) pathway, and
      examined which frequency field oscillations were mostly related to the cognitive
      deficiency in depression. Two novel algorithms were employed to determine the
      coupling interaction between the LD thalamus and medial prefrontal cortex (mPFC)
      in five frequency bands, using the phase signals of local field potentials (LFP)
      in these two regions. The results showed that the power of neural activity in
      mPFC was increased in delta, theta and beta frequency bands in depression.
      However, the nonlinear characteristics of LFP activity were weakened in
      depression by means of sample entropy measurements. In the analysis of phase
      dynamics, the phase synchronization values were reduced in theta rhythm in
      stressed rats. Importantly, the coupling direction index d and the unidirectional
      influence from LD thalamus to mPFC were significantly reduced at the theta rhythm
      in rats in depression, and increased after memantine treatment, which were
      associated with the LTP alterations and cognitive impairment in our previous
      report. Moreover, the fact that the reduced entropy value was only found in mPFC
      might implicate postsynaptic effect involved in synaptic plasticity alteration in
      the depression model. The results suggest that the effects of depression on
      cognitive deficits are mediated via profound alterations in information flow in
      the TC pathway, and the directional index at theta rhythm could be used as a
      measurement of synaptic plasticity.

PMID- 22648381
TI  - Abnormal isoaspartyl residues in erythrocyte membranes from psoriatic patients.
AB  - Spontaneous protein deamidation of labile asparagines (Asn), generating abnormal
      isoaspartyl residues (IsoAsp), is associated with cell aging and enhanced by an
      oxidative microenvironment. The presence of isopeptide bonds impairs protein
      structure/function and can trigger autoimmune responses. To minimize the damage,
      IsoAsp can be "repaired" by a specific L-isoaspartate-(D-aspartate)-protein-O
      methyltransferase. The condition of chronic oxidative stress reported in
      psoriatic patients, and the potential etiological role of unknown self-antigens,
      prompted us to investigate Asn deamidation in psoriatic tissues. Erythrocytes
      (RBC) were selected as the model system since, lacking protein synthesis
      apparatus, they are unable to replace damaged proteins. Blood samples were
      obtained from 36 patients and 34 controls. L-isoAsp content was highly increased
      in RBC membrane proteins from psoriatic patients. Deamidated species included
      ankyrin, band 4.1, band 4.2 and the integral membrane protein band 3. A
      functional analysis demonstrated that this result was unrelated to a reduced
      efficiency of the S-adenosylmethionine-dependent repair system suggesting an
      increased protein instability at Asn sites, responsible for IsoAsp accumulation
      in psoriatic patients.

PMID- 22648382
TI  - The conductive hearing loss due to an experimentally induced middle ear effusion
      alters the interaural level and time difference cues to sound location.
AB  - Otitis media with effusion (OME) is a pathologic condition of the middle ear that
      leads to a mild to moderate conductive hearing loss as a result of fluid in the
      middle ear. Recurring OME in children during the first few years of life has been
      shown to be associated with poor detection and recognition of sounds in noisy
      environments, hypothesized to result due to altered sound localization cues. To
      explore this hypothesis, we simulated a middle ear effusion by filling the middle
      ear space of chinchillas with different viscosities and volumes of silicone oil
      to simulate varying degrees of OME. While the effects of middle ear effusions on
      the interaural level difference (ILD) cue to location are known, little is known
      about whether and how middle ear effusions affect interaural time differences
      (ITDs). Cochlear microphonic amplitudes and phases were measured in response to
      sounds delivered from several locations in azimuth before and after filling the
      middle ear with fluid. Significant attenuations (20-40 dB) of sound were observed
      when the middle ear was filled with at least 1.0 ml of fluid with a viscosity of
      3.5 Poise (P) or greater. As expected, ILDs were altered by ~30 dB. Additionally,
      ITDs were shifted by ~600 MUs for low frequency stimuli (<4 kHz) due to a delay
      in the transmission of sound to the inner ear. The data show that in an
      experimental model of OME, ILDs and ITDs are shifted in the spatial direction of
      the ear without the experimental effusion.

PMID- 22648383
TI  - Influence of health insurance coverage on breast, cervical, and colorectal cancer
      screening in rural primary care settings.
AB  - BACKGROUND: The current study was performed to determine, in rural settings, the
      relation between the type and status of insurance coverage and being up-to-date
      for breast, cervical, and colorectal cancer screening. METHODS: Four primary care
      practices in 2 rural Oregon communities participated. Medical chart reviews that
      were conducted between October 2008 and August 2009 assessed insurance coverage
      and up-to-date status for breast, cervical, and colorectal cancer screening.
      Inclusion criteria involved having at least 1 health care visit within the past 5
      years and being aged >= 55 years. RESULTS: The majority of patients were women
      aged 55 years to 70 years, employed or retired, and who had private health
      insurance and an average of 2.5 comorbid conditions. The overall percentage of
      eligible women who were up-to-date for cervical cancer screening was 30%;
      approximately 27% of women were up-to-date for clinical breast examination, 37%
      were up-to-date for mammography, and 19% were up-to-date for both mammography and
      clinical breast examination. Approximately 38% of men and 35% of women were up-to
      date for colorectal cancer screening using any test at appropriate screening
      intervals. In general, having any insurance versus being uninsured was associated
      with undergoing cancer screening. For each type of screening, patients who had at
      least 1 health maintenance visit were significantly more likely to be up-to-date
      compared with those with no health maintenance visits. A significant interaction
      was found between having health maintenance visits, having any health insurance,
      and being up-to-date for cancer screening tests. CONCLUSIONS: Overall, the
      percentage of patients who were up-to-date for any cancer screening, especially
      cervical cancer screening, was found to be very low in rural Oregon. Patients
      with some form of health insurance were more likely to have had a health
      maintenance visit within the previous 2 years and to be up-to-date for breast,
      cervical, and/or colorectal cancer screening.

PMID- 22648385
TI  - Body composition and circulating high-molecular-weight adiponectin and IGF-I in
      infants born small for gestational age: breast- versus formula-feeding.
AB  - Prenatal growth restraint, if followed by postnatal overweight, confers risk for
      adult disease including diabetes. The mechanisms whereby neonatal nutrition may
      modulate such risk are poorly understood. We studied the effects of nutrition
      (breast-feeding [BRF] vs. formula-feeding [FOF]) on weight partitioning and
      endocrine state (as judged by high-molecular-weight [HMW] adiponectin and IGF-I)
      of infants born small for gestational age (SGA). Body composition (by
      absorptiometry), HMW adiponectin, and IGF-I were assessed at birth and 4 months
      in BRF infants born appropriate for gestational age (AGA; n = 72) and SGA infants
      receiving BRF (n = 46) or FOF (n = 56), the latter being randomized to receive a
      standard (FOF1) or protein-rich formula (FOF2). Compared with AGA-BRF infants,
      the catchup growth of SGA infants was confined to lean mass, independently of
      nutrition. Compared with AGA-BRF infants, SGA-BRF infants had normal HMW
      adiponectin and IGF-I levels at 4 months, whereas SGA-FOF infants had elevated
      levels of HMW adiponectin (particularly SGA-FOF1) and IGF-I (particularly SGA
      FOF2). In conclusion, neonatal nutrition seems to influence endocrinology more
      readily than body composition of SGA infants. Follow-up will disclose whether the
      endocrine abnormalities in SGA-FOF infants can serve as early markers of an
      unfavorable metabolic course and whether they may contribute to design early
      interventions that prevent subsequent disease, including diabetes.

PMID- 22648386
TI  - Famine exposure in the young and the risk of type 2 diabetes in adulthood.
AB  - The developmental origins hypothesis proposes that undernutrition during early
      development is associated with an increased type 2 diabetes risk in adulthood. We
      investigated the association between undernutrition during childhood and young
      adulthood and type 2 diabetes in adulthood. We studied 7,837 women from Prospect
      EPIC (European Prospective Investigation Into Cancer and Nutrition) who were
      exposed to the 1944-1945 Dutch famine when they were between age 0 and 21 years.
      We used Cox proportional hazards regression models to explore the effect of
      famine on the risk of subsequent type 2 diabetes in adulthood. We adjusted for
      potential confounders, including age at famine exposure, smoking, and level of
      education. Self-reported famine exposure during childhood and young adulthood was
      associated with an increased type 2 diabetes risk in a dose-dependent manner. In
      those who reported moderate famine exposure, the age-adjusted type 2 diabetes
      hazard ratio (HR) was 1.36 (95% CI [1.09-1.70]); in those who reported severe
      famine exposure, the age-adjusted HR was 1.64 (1.26-2.14) relative to unexposed
      women. These effects did not change after adjustment for confounders. This study
      provides the first direct evidence, using individual famine exposure data, that a
      short period of moderate or severe undernutrition during postnatal development
      increases type 2 diabetes risk in adulthood.

PMID- 22648388
TI  - Osterix is required for Sonic hedgehog-induced osteoblastic MC3T3-E1 cell
      differentiation.
AB  - It has been shown that hedgehog (Hh) signaling plays an important role during
      bone development. However, the mechanism(s) by which Hh stimulates osteoblast
      differentiation are not fully elucidated. This study was performed to examine if
      Sonic hedgehog (Shh) affects osteoblast differentiation in osteoblastic MC3T3-E1
      cells and determine the exact role of osterix (Osx) involved in Hh-induced
      osteoblast differentiation. Our real-time RT-PCR result shows that Shh
      significantly induced osteoblast differentiation by up-regulation of osteocalcin,
      alkaline phosphatase, bone sialoprotein, Type I collagen, runt-related
      transcription factor 2 (Runx2), and Osx RNA expression in MC3T3-E1 cells. ALP
      protein activity, Osx protein expression, as well as Osx promoter activity was
      also enhanced by Shh treatment in cell culture. Interestingly, Shh-induced Osx up
      regulation was only slightly affected by knocking down Runx2 using siRNA in cells
      within 3 days of culture, however, knocking down Osx expression in cells totally
      blocked Shh-induced osteoblast differentiation. These findings demonstrate for
      the first time that Shh stimulates early osteoblast differentiation mainly
      through up-regulation of the expression of Osx in osteoblastic MC3T3-E1 cells in
      both Runx2-dependent and Runx2-independent manner.

PMID- 22648387
TI  - A novel anti-inflammatory role for spleen-derived interleukin-10 in obesity
      induced inflammation in white adipose tissue and liver.
AB  - Obesity is associated with systemic low-grade inflammation and obesity-related
      metabolic disorders. Considering that obesity decreases the expression of
      proinflammatory cytokines in the spleen, we assessed the role of interleukin (IL)
      10, an anti-inflammatory cytokine produced by the spleen, in the pathogenesis of
      obesity. Changes in obesity-related pathogenesis, including inflammatory
      responses in multiple organs, were assessed after systemic administration of
      exogenous IL-10 to splenectomy (SPX)-treated obese wild-type and IL-10 knockout
      (IL-10KO) mice. Obesity resulted in the inability of the spleen to synthesize
      cytokines, including IL-10, and proinflammatory cytokines in obesity are then
      likely to emerge from tissues other than the spleen because serum levels of IL
      10, but not proinflammatory cytokines, decreased despite the expression of these
      cytokines in the spleen being reduced in high fat-induced obese mice. SPX
      aggravated the inflammatory response in white adipose tissue (WAT) and the liver
      and suppressed adiposity in WAT. However, it accentuated adiposity in the liver.
      These SPX-induced changes were inhibited by systemic administration of IL-10.
      Moreover, SPX had little effect on the inflammatory responses in WAT and the
      liver of IL-10KO mice. These data show the role of spleen-derived IL-10 in diet
      induced changes as a result of inflammatory responses in WAT and the liver.

PMID- 22648389
TI  - High temperature nucleation and growth of glutathione protected ~Ag75 clusters.
AB  - We report the first high temperature solution state synthesis of glutathione (
      SG) protected atomically precise silver clusters. Noble metal cluster synthesis
      from metal ions generally requires ice cold temperatures as they are extremely
      sensitive and high temperature routes are used only for core reduction methods,
      starting from nanoparticles. The clusters formed by the new route have distinct
      features in their absorption profile and they exhibit red luminescence. They are
      characterised by other spectroscopic and microscopic techniques and a tentative
      formula of Ag(75)(SG)(40) has been assigned.

PMID- 22648390
TI  - Doxycycline sclerotherapy in children with lymphatic malformations: outcomes,
      complications and clinical efficacy.
AB  - BACKGROUND: Lymphatic malformations (LMs) are congenital lesions of the lymphatic
      system and consist of lymphatic channels and cystic spaces of varying sizes.
      Recent evidence has shown that LMs respond well to intralesional sclerotherapy.
      OBJECTIVE: The purpose of this retrospective study is to evaluate the outcome and
      efficacy of using doxycycline in treating macrocystic, microcystic and combined
      macro- and microcystic LMs in a tertiary-care pediatric center. MATERIALS AND
      METHODS: Fifty children (32 boys, 18 girls) underwent doxycycline sclerotherapy
      for treatment of LMs between January 2005 and October 2010. Demographics,
      imaging, doxycycline treatment details, complications and follow-up details were
      documented. RESULTS: The mean age at first treatment was 5.9 years (3 days-17.8
      years), median 4.2 years. Cervicofacial (19/50 children) and truncal (16/50
      children) locations were the most frequently affected. One hundred forty-six
      sclerotherapy sessions were performed in 50 children (mean 2.9/child). The mean
      doxycycline dose/kg body weight for 146 sessions was 15.3 mg/kg (0.6-85.7 mg/kg).
      Complications occurred in 4/146 procedures. Clinical follow-up showed excellent
      response in 14/16 children with macrocystic LMs, 21/27 children with combined LMs
      and 4/7 children with microcystic LMs. CONCLUSION: Doxycycline is a safe and
      effective sclerosant agent for treating LMs in children, with a low complication
      rate.

PMID- 22648391
TI  - Congenital midline nasofrontal masses.
AB  - Congenital midline nasal masses are uncommon anomalies including nasal
      dermoids/epidermoids, nasal glial heterotopias and encephaloceles. These lesions
      can occur at the nasal bridge, extend intranasally and have intracranial
      extension with communication to the subarachnoid space. Therefore, accurate
      diagnosis of these lesions is critically important for presurgical planning and
      prevention of potentially fatal complications. Neuroimaging is essential in the
      evaluation of congenital midline nasal masses to identify the specific type of
      lesion, evaluate for the presence of intracranial extension and allow for
      appropriate presurgical planning.

PMID- 22648392
TI  - Driving reaction time before and after surgery for lumbar disc herniation in
      patients with radiculopathy.
AB  - PURPOSE: Although patients scheduled to undergo lumbar disc surgery often ask
      when they are allowed to drive a motor vehicle again, there are no published
      recommendations on this subject. METHODS: We conducted a prospective study in 46
      consecutive patients (mean age 48.9 years) to determine driving reaction time
      (DRT) before and after surgery in patients with lumbar disc herniation. Of the
      patients 23 had left-side radiculopathy and 23 right-side radiculopathy. Driving
      reaction time as well as back and leg pain were evaluated preoperatively, on the
      day of discharge from hospital and at the 5-week follow-up examination (FU). 31
      healthy subjects were tested as controls. RESULTS: Significant improvement in DRT
      was seen for both patient samples (p < 0.05). For patients with a right-side
      radiculopathy preoperative DRT was 664 ms (median, IQR: 241), which was reduced
      to 605 ms (median, IQR: 189) immediately postoperatively and to 593 ms (median,
      IQR: 115) at FU. For patients with a left-side radiculopathy DRT was 675 ms
      (median, IQR: 247) preoperatively, 638 ms (median, IQR: 242) postoperatively and
      619 ms (median, IQR: 162) at FU. Pain was moderately correlated to DRT. Control
      subjects had a driving reaction time of 487 (median, IQR: 116), which differed
      significantly from patients at all three testing times (p < 0.001). CONCLUSION:
      Our data indicate a positive effect of the surgery on driving ability. Therefore,
      we would suggest that for both patient samples it is safe to continue driving
      after hospital discharge. However, patients have to be informed about increased
      DRT caused by radiculopathy already before surgery.

PMID- 22648394
TI  - Oxygen-enhanced magnetic resonance imaging of the brain:  a rodent model.
AB  - Oxygen-enhanced MRI has been shown to be a viable alternative to hyperpolarized
      gases for pulmonary imaging. The changes in the relaxation times due to hyperoxic
      conditions in the blood pool induced by inhalation of pure oxygen have produced
      sufficient signal changes for imaging applications. This is a safe and low-cost
      alternative for contrast-enhanced imaging. The application of oxygen-enhanced MRI
      in brain imaging has been much less studied. In this study, we investigated the
      changes in the relaxation times in the brain due to inhalation of pure oxygen in
      a rodent model. We also assessed the effects of reduced blood flow due to
      hyperoxic conditions. Despite the reduced blood flow, significant changes in T1,
      T2, and T2* relaxation times were detected. We conclude that oxygen-enhanced MRI
      can be used in rodent models of disease.

PMID- 22648395
TI  - High hopes: can molecular electronics realise its potential?
AB  - Manipulating and controlling the self-organisation of small collections of
      molecules, as an alternative to investigating individual molecules, has motivated
      researchers bent on processing and storing information in molecular electronic
      devices (MEDs). Although numerous ingenious examples of single-molecule devices
      have provided fundamental insights into their molecular electronic properties,
      MEDs incorporating hundreds to thousands of molecules trapped between wires in
      two-dimensional arrays within crossbar architectures offer a glimmer of hope for
      molecular memory applications. In this critical review, we focus attention on the
      collective behaviour of switchable mechanically interlocked molecules (MIMs)-
      specifically, bistable rotaxanes and catenanes--which exhibit reset lifetimes
      between their ON and OFF states ranging from seconds in solution to hours in
      crossbar devices. When these switchable MIMs are introduced into high viscosity
      polymer matrices, or self-assembled as monolayers onto metal surfaces, both in
      the form of nanoparticles and flat electrodes, or organised as tightly packed
      islands of hundreds and thousands of molecules sandwiched between two electrodes,
      the thermodynamics which characterise their switching remain approximately
      constant while the kinetics associated with their reset follow an intuitively
      predictable trend--that is, fast when they are free in solution and sluggish when
      they are constrained within closely packed monolayers. The importance of seamless
      interactions and constant feedback between the makers, the measurers and the
      modellers in establishing the structure-property relationships in these
      integrated functioning systems cannot be stressed enough as rationalising the
      many different factors that impact device performance becomes more and more
      demanding. The choice of electrodes, as well as the self-organised
      superstructures of the monolayers of switchable MIMs employed in the molecular
      switch tunnel junctions (MSTJs) associated with the crossbars of these MEDs, have
      a profound influence on device operation and performance. It is now clear, after
      much investigation, that a distinction should be drawn between two types of
      switching that can be elicited from MSTJs. One affords small ON/OFF ratios and is
      a direct consequence of the switching in bistable MIMs that leads to a relatively
      small remnant molecular signature--an activated chemical process. The other leads
      to a very much larger signature and ON/OFF ratios resulting from physical or
      chemical changes in the electrodes themselves. Control experiments with various
      compounds, including degenerate catenanes and free dumbbells, which cannot and do
      not switch, are crucial in establishing the authenticity of the small ON/OFF
      ratios and remnant molecular signatures produced by bistable MIMs. Moreover,
      experiments conducted on monolayers in MSTJs of molecules designed to switch and
      molecules designed not to switch have been probed directly by spectroscopic and
      other means in support of MEDs that store information through switching
      collections of bistable MIMs contained in arrays of MSTJs. In the quest for the
      next generation of MEDs, it is likely that monolayers of bistable MIMs will be
      replaced by robust crystalline extended structures wherein the switchable
      components, derived from bistable MIMs, are organised precisely in a periodic
      manner.

PMID- 22648396
TI  - Histological comparison of the candidate arteries for bypass grafting of the
      posterior interventricular artery.
AB  - This study evaluated five vessels as potential candidates for coronary artery
      bypass grafting at the posterior interventricular artery (PIVA) blockage site. We
      used light microscopy and digital image analysis of H&E and Van Gieson's-stained
      slides to investigate luminal diameter, arterial wall thickness, and relative
      muscularity and elasticity of candidate vessels. Results from our sample indicate
      that the inferior epigastric artery (IEA) may be the preferred graft to the PIVA
      based on overall similarities in these measurements. Other arteries provided a
      favorable match based on a single measurement, but the IEA agreed most
      consistently with the PIVA. When choosing a vessel to bypass blockage at the
      PIVA, cardiothoracic surgeons should be aware of the many favorable features of
      the IEA.

PMID- 22648397
TI  - CePO4:Tb,Gd hollow nanospheres as peroxidase mimic and magnetic-fluorescent
      imaging agent.
AB  - Solvothermally synthesized CePO(4):Tb,Gd hollow nanospheres were fabricated as a
      peroxidase mimic and bimodal magnetic-fluorescent imaging agent, which show
      potential applications in biocatalysis and bioimaging.

PMID- 22648404
TI  - The role of cyclobutenes in gold(I)-catalysed skeletal rearrangement of 1,6
      enynes.
AB  - 1,6-Enynes with electron-donating substituents at the alkyne undergo gold(I)
      catalysed single cleavage skeletal rearrangement, whereas substrates with
      electron-withdrawing substituents evolve selectively to double cleavage
      rearrangement. Theoretical calculations provide a qualitative rationale for these
      effects, and suggest that bicyclo[3.2.0]hept-5-enes are involved as
      intermediates. We provide the first X-ray structural evidence for the formation
      of a product of this class in a cycloisomerisation of a 1,6-enyne.

PMID- 22648398
TI  - Aging and substitutive hormonal therapy influence in regional and subcellular
      distribution of ERalpha in female rat brain.
AB  - Estrogens are not only critical for sexual differentiation it is well-known for
      the role of 17beta-estradiol (E2) in the adult brain modulating memory, learning,
      mood and acts as a neuroprotector. E2 exerts its actions through two classical
      receptors: estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta).
      The distribution of both receptors changes from one brain area to another, E2
      being able to modulate their expression. Among the classical features of aging in
      humans, we find cognitive impairment, dementia, memory loss, etc. As estrogen
      levels change with age, especially in females, it is important to know the
      effects of low E2 levels on ERalpha distribution; results from previous studies
      are controversial regarding this issue. In the present work, we have studied the
      effects of long-term E2 depletion as well as the ones of E2 treatment on ERalpha
      brain distribution of ovariectomized rats along aging in the diencephalon and in
      the telencephalon. We have found that ovariectomy causes downregulation and
      affects subcellular localization of ERalpha expression during aging, meanwhile
      prolonged estrogen treatment produces upregulation and overexpression of the
      receptor levels. Our results support the idea of the region-specific
      neuroprotection mechanisms mediated by estradiol.

PMID- 22648405
TI  - Hyperfractionated accelerated radiotherapy with concomitant integrated boost of
      70-75 Gy in 5 weeks for advanced head and neck cancer. A phase I dose escalation
      study.
AB  - BACKGROUND AND PURPOSE: The present study was performed to evaluate the
      feasibility of a new, 5-week regimen of 70-75 Gy hyperfractionated accelerated
      radiotherapy with concomitant integrated boost (HARTCIB) for locally advanced,
      inoperable head and neck cancer. METHODS AND MATERIALS: A total of 39 patients
      with very advanced, stage IV nonmetastatic head and neck squamous cell carcinoma
      (median gross tumor volume 72 ml) were included in this phase I dose escalation
      study. A total of 50 fractions intensity-modulated radiotherapy (IMRT) were
      administered twice daily over 5 weeks. Prescribed total dose/dose per fraction
      for planning target volume (PTV(tumor)) were 70 Gy in 1.4 Gy fractions, 72.5 Gy
      in 1.45 Gy fractions, and 75 Gy in 1.5 Gy fractions for 10, 13, and 16 patients,
      respectively. Uninvolved lymphatic nodes (PTV(uninvolved)) were irradiated with
      55 Gy in 1.1 Gy fractions using the concomitant integrated boost. RESULTS: Acute
      toxicity was evaluated according to the RTOG/EORTC scale; the incidence of grade
      3 mucositis was 51% in the oral cavity/pharynx and 0% in skin and the recovery
      time was <= 9 weeks for all patients. Late toxicity was evaluated in patients in
      complete remission according to the RTOG/EORTC scale. No grade 3/4 late toxicity
      was observed. The 1-year locoregional progression-free survival was 50% and
      overall survival was 55%. CONCLUSION: HARTCIB (75 Gy in 5 weeks) is feasible for
      patients deemed unsuitable for chemoradiation. Acute toxicity was lower than
      predicted from radiobiological models; duration of dysphagia and confluent
      mucositis were particularly short. Better conformity of radiotherapy allows the
      use of more intensive altered fractionation schedules compared with older
      studies. These results suggest that further dose escalation might be possible
      when highly conformal techniques (e.g., stereotactic radiotherapy) are used.

PMID- 22648406
TI  - Occurrence of a bacterial membrane microdomain at the cell division site enriched
      in phospholipids with polyunsaturated hydrocarbon chains.
AB  - In this study, we found that phospholipids containing an eicosapentaenyl group
      form a novel membrane microdomain at the cell division site of a Gram-negative
      bacterium, Shewanella livingstonensis Ac10, using chemically synthesized
      fluorescent probes. The occurrence of membrane microdomains in eukaryotes and
      prokaryotes has been demonstrated with various imaging tools for phospholipids
      with different polar headgroups. However, few studies have focused on the
      hydrocarbon chain-dependent localization of membrane-resident phospholipids in
      vivo. We previously found that lack of eicosapentaenoic acid (EPA), a
      polyunsaturated fatty acid found at the sn-2 position of glycerophospholipids,
      causes a defect in cell division after DNA replication of S. livingstonensis
      Ac10. Here, we synthesized phospholipid probes labeled with a fluorescent 7-nitro
      2,1,3-benzoxadiazol-4-yl (NBD) group to study the localization of EPA-containing
      phospholipids by fluorescence microscopy. A fluorescent probe in which EPA was
      bound to the glycerol backbone via an ester bond was found to be unsuitable for
      imaging because EPA was released from the probe by in vivo hydrolysis. To
      overcome this problem, we synthesized hydrolysis-resistant ether-type
      phospholipid probes. Using these probes, we found that the fluorescence localized
      between two nucleoids at the cell center during cell division when the cells were
      grown in the presence of the eicosapentaenyl group-containing probe (N-NBD-1
      oleoyl-2-eicosapentaenyl-sn-glycero-3-phosphoethanolamine), whereas this
      localization was not observed with the oleyl group-containing control probe (N
      NBD-1-oleoyl-2-oleyl-sn-glycero-3-phosphoethanolamine). Thus, phospholipids
      containing an eicosapentaenyl group are specifically enriched at the cell
      division site. Formation of a membrane microdomain enriched in EPA-containing
      phospholipids at the nucleoid occlusion site probably facilitates cell division.

PMID- 22648407
TI  - Targeting Toll-like receptor (TLR) signaling by Toll/interleukin-1 receptor (TIR)
      domain-containing adapter protein/MyD88 adapter-like (TIRAP/Mal)-derived decoy
      peptides.
AB  - Toll/interleukin-1 receptor (TIR) domain-containing adapter protein/MyD88 adapter
      like (TIRAP/Mal) is an adapter protein that facilitates recruitment of MyD88 to
      TLR4 and TLR2 signaling complexes. We previously generated a library of cell
      permeating TLR4 TIR-derived decoy peptides fused to the translocating segment of
      the Drosophila Antennapedia homeodomain and examined each peptide for the ability
      to inhibit TLR4 signaling (Toshchakov, V. Y., Szmacinski, H., Couture, L. A.,
      Lakowicz, J. R., and Vogel, S. N. (2011) J. Immunol. 186, 4819-4827). We have now
      expanded this study to test TIRAP decoy peptides. Five TIRAP peptides, TR3 (for
      TIRAP region 3), TR5, TR6, TR9, and TR11, inhibited LPS-induced cytokine mRNA
      expression and MAPK activation. Inhibition was confirmed at the protein level;
      select peptides abolished the LPS-induced cytokine production measured in cell
      culture 24 h after a single treatment. Two of the TLR4 inhibitory peptides, TR3
      and TR6, also inhibited cytokine production induced by a TLR2/TLR1 agonist, S
      (2,3-bis(palmitoyloxy)-(2R,2S)-propyl)-N-palmitoyl-(R)-Cys-Ser-Lys(4)-OH;
      however, a higher peptide concentration was required to achieve comparable
      inhibition of TLR2 versus TLR4 signaling. Two TLR4 inhibitory peptides, TR5 and
      TR6, were examined for the ability to inhibit TLR4-driven cytokine induction in
      mice. Pretreatment with either peptide significantly reduced circulating TNF
      alpha and IL-6 in mice following LPS injection. This study has identified novel
      TLR inhibitory peptides that block cellular signaling at low micromolar
      concentrations in vitro and in vivo. Comparison of TLR4 inhibition by TLR4 and
      TIRAP TIR-derived peptides supports the view that structurally diverse regions
      mediate functional interactions of TIR domains.

PMID- 22648408
TI  - Product binding varies dramatically between processive and nonprocessive
      cellulase enzymes.
AB  - Cellulases hydrolyze beta-1,4 glycosidic linkages in cellulose, which are among
      the most prevalent and stable bonds in Nature. Cellulases comprise many glycoside
      hydrolase families and exist as processive or nonprocessive enzymes. Product
      inhibition negatively impacts cellulase action, but experimental measurements of
      product-binding constants vary significantly, and there is little consensus on
      the importance of this phenomenon. To provide molecular level insights into
      cellulase product inhibition, we examine the impact of product binding on
      processive and nonprocessive cellulases by calculating the binding free energy of
      cellobiose to the product sites of catalytic domains of processive and
      nonprocessive enzymes from glycoside hydrolase families 6 and 7. The results
      suggest that cellobiose binds to processive cellulases much more strongly than
      nonprocessive cellulases. We also predict that the presence of a cellodextrin
      bound in the reactant site of the catalytic domain, which is present during
      enzymatic catalysis, has no effect on product binding in nonprocessive
      cellulases, whereas it significantly increases product binding to processive
      cellulases. This difference in product binding correlates with hydrogen bonding
      between the substrate-side ligand and the cellobiose product in processive
      cellulase tunnels and the additional stabilization from the longer tunnel-forming
      loops. The hydrogen bonds between the substrate- and product-side ligands are
      disrupted by water in nonprocessive cellulase clefts, and the lack of long tunnel
      forming loops results in lower affinity of the product ligand. These findings
      provide new insights into the large discrepancies reported for binding constants
      for cellulases and suggest that product inhibition will vary significantly based
      on the amount of productive binding for processive cellulases on cellulose.

PMID- 22648409
TI  - The Skp1 protein from Toxoplasma is modified by a cytoplasmic prolyl 4
      hydroxylase associated with oxygen sensing in the social amoeba Dictyostelium.
AB  - In diverse types of organisms, cellular hypoxic responses are mediated by prolyl
      4-hydroxylases that use O(2) and alpha-ketoglutarate as substrates to hydroxylate
      conserved proline residues in target proteins. Whereas in metazoans these enzymes
      control the stability of the HIFalpha family of transcription factor subunits,
      the Dictyostelium enzyme (DdPhyA) contributes to O(2) regulation of development
      by a divergent mechanism involving hydroxylation and subsequent glycosylation of
      DdSkp1, an adaptor subunit in E3(SCF) ubiquitin ligases. Sequences related to
      DdPhyA, DdSkp1, and the glycosyltransferases that cap Skp1 hydroxyproline occur
      also in the genomes of Toxoplasma and other protists, suggesting that this O(2)
      sensing mechanism may be widespread. Here we show by disruption of the TgphyA
      locus that this enzyme is required for Skp1 glycosylation in Toxoplasma and that
      disrupted parasites grow slowly at physiological O(2) levels. Conservation of
      cellular function was tested by expression of TgPhyA in DdphyA-null cells. Simple
      gene replacement did not rescue Skp1 glycosylation, whereas overexpression not
      only corrected Skp1 modification but also restored the O(2) requirement to a
      level comparable to that of overexpressed DdPhyA. Bacterially expressed TgPhyA
      protein can prolyl hydroxylate both Toxoplasma and Dictyostelium Skp1s. Kinetic
      analyses showed that TgPhyA has similar properties to DdPhyA, including a
      superimposable dependence on the concentration of its co-substrate alpha
      ketoglutarate. Remarkably, however, TgPhyA had a significantly higher apparent
      affinity for O(2). The findings suggest that Skp1 hydroxylation by PhyA is a
      conserved process among protists and that this biochemical pathway may indirectly
      sense O(2) by detecting the levels of O(2)-regulated metabolites such as alpha
      ketoglutarate.

PMID- 22648410
TI  - Hemerythrin-like domain within F-box and leucine-rich repeat protein 5 (FBXL5)
      communicates cellular iron and oxygen availability by distinct mechanisms.
AB  - Iron regulatory proteins play a principal role in maintaining cellular iron
      homeostasis by post-transcriptionally regulating factors responsible for iron
      uptake, utilization, and storage. An E3 ubiquitin ligase complex containing FBXL5
      targets IRP2 for proteasomal degradation under iron- and oxygen-replete
      conditions, whereas FBXL5 itself is degraded when iron and oxygen availability
      decreases. FBXL5 contains a hemerythrin-like (Hr) domain at its N terminus that
      mediates its own differential stability. Here, we investigated the iron- and
      oxygen-dependent conformational changes within FBXL5-Hr that underlie its role as
      a cellular sensor. As predicted, FBXL5-Hr undergoes substantive structural
      changes when iron becomes limiting, accounting for its switch-like behavior.
      However, these same changes are not observed in response to oxygen depletion,
      indicating that this domain accommodates two distinct sensing mechanisms.
      Moreover, FBXL5-Hr does not behave as a dynamic sensor that continuously samples
      the cellular environment, assuming conformations in equilibrium with ever
      changing cellular iron levels. Instead, the isolated domain appears competent to
      incorporate iron only at or near the time of its own synthesis. These
      observations have important implications for mechanisms by which these
      metabolites are sensed within mammalian cells.

PMID- 22648411
TI  - Streptococcal surface proteins activate the contact system and control its
      antibacterial activity.
AB  - Group G streptococci (GGS) are important bacterial pathogens in humans. Here, we
      investigated the interactions between GGS and the contact system, a procoagulant
      and proinflammatory proteolytic cascade that, upon activation, also generates
      antibacterial peptides. Two surface proteins of GGS, protein FOG and protein G
      (PG), were found to bind contact system proteins. Experiments utilizing contact
      protein-deficient human plasma and isogenic GGS mutant strains lacking FOG or PG
      showed that FOG and PG both activate the procoagulant branch of the contact
      system. In contrast, only FOG induced cleavage of high molecular weight
      kininogen, generating the proinflammatory bradykinin peptide and additional high
      molecular weight kininogen fragments containing the antimicrobial peptide NAT-26.
      On the other hand, PG protected the bacteria against the antibacterial effect of
      NAT-26. These findings underline the significance of the contact system in innate
      immunity and demonstrate that GGS have evolved surface proteins to exploit and
      modulate its effects.

PMID- 22648413
TI  - Kinetic partitioning between synthetic and editing pathways in class I aminoacyl
      tRNA synthetases occurs at both pre-transfer and post-transfer hydrolytic steps.
AB  - Comprehensive steady-state and transient kinetic studies of the synthetic and
      editing activities of Escherichia coli leucyl-tRNA synthetase (LeuRS) demonstrate
      that the enzyme depends almost entirely on post-transfer editing to endow the
      cell with specificity against incorporation of norvaline into protein. Among the
      three class I tRNA synthetases possessing a dedicated post-transfer editing
      domain (connective peptide 1; CP1 domain), LeuRS resembles valyl-tRNA synthetase
      in its reliance on post-transfer editing, whereas isoleucyl-tRNA synthetase
      differs in retaining a distinct tRNA-dependent synthetic site pre-transfer
      editing activity to clear noncognate amino acids before misacylation. Further
      characterization of the post-transfer editing activity in LeuRS by single
      turnover kinetics demonstrates that the rate-limiting step is dissociation of
      deacylated tRNA and/or amino acid product and highlights the critical role of a
      conserved aspartate residue in mediating the first-order hydrolytic steps on the
      enzyme. Parallel analyses of adenylate and aminoacyl-tRNA formation reactions by
      wild-type and mutant LeuRS demonstrate that the efficiency of post-transfer
      editing is controlled by kinetic partitioning between hydrolysis and dissociation
      of misacylated tRNA and shows that trans editing after rebinding is a competent
      kinetic pathway. Together with prior analyses of isoleucyl-tRNA synthetase and
      valyl-tRNA synthetase, these experiments provide the basis for a comprehensive
      model of editing by class I tRNA synthetases, in which kinetic partitioning plays
      an essential role at both pre-transfer and post-transfer steps.

PMID- 22648412
TI  - trans-(-)-epsilon-Viniferin increases mitochondrial sirtuin 3 (SIRT3), activates
      AMP-activated protein kinase (AMPK), and protects cells in models of Huntington
      Disease.
AB  - Huntington disease (HD) is an inherited neurodegenerative disorder caused by an
      abnormal polyglutamine expansion in the protein Huntingtin (Htt). Currently, no
      cure is available for HD. The mechanisms by which mutant Htt causes neuronal
      dysfunction and degeneration remain to be fully elucidated. Nevertheless,
      mitochondrial dysfunction has been suggested as a key event mediating mutant Htt
      induced neurotoxicity because neurons are energy-demanding and particularly
      susceptible to energy deficits and oxidative stress. SIRT3, a member of sirtuin
      family, is localized to mitochondria and has been implicated in energy
      metabolism. Notably, we found that cells expressing mutant Htt displayed reduced
      SIRT3 levels. trans-(-)-epsilon-Viniferin (viniferin), a natural product among
      our 22 collected naturally occurring and semisynthetic stilbenic compounds,
      significantly attenuated mutant Htt-induced depletion of SIRT3 and protected
      cells from mutant Htt. We demonstrate that viniferin decreases levels of reactive
      oxygen species and prevents loss of mitochondrial membrane potential in cells
      expressing mutant Htt. Expression of mutant Htt results in decreased deacetylase
      activity of SIRT3 and further leads to reduction in cellular NAD(+) levels and
      mitochondrial biogenesis in cells. Viniferin activates AMP-activated kinase and
      enhances mitochondrial biogenesis. Knockdown of SIRT3 significantly inhibited
      viniferin-mediated AMP-activated kinase activation and diminished the
      neuroprotective effects of viniferin, suggesting that SIRT3 mediates the
      neuroprotection of viniferin. In conclusion, we establish a novel role for
      mitochondrial SIRT3 in HD pathogenesis and discovered a natural product that has
      potent neuroprotection in HD models. Our results suggest that increasing
      mitochondrial SIRT3 might be considered as a new therapeutic approach to
      counteract HD, as well as other neurodegenerative diseases with similar
      mechanisms.

PMID- 22648414
TI  - A novel mechanism of growth phase-dependent tolerance to isoniazid in
      mycobacteria.
AB  - Tuberculosis remains one of the most deadly infectious diseases worldwide and is
      a leading public health problem. Although isoniazid (INH) is a key drug for the
      treatment of tuberculosis, tolerance to INH necessitates prolonged treatment,
      which is a concern for effective tuberculosis chemotherapy. INH is a prodrug that
      is activated by the mycobacterial enzyme, KatG. Here, we show that mycobacterial
      DNA-binding protein 1 (MDP1), which is a histone-like protein conserved in
      mycobacteria, negatively regulates katG transcription and leads to phenotypic
      tolerance to INH in mycobacteria. Mycobacterium smegmatis deficient for MDP1
      exhibited increased expression of KatG and showed enhanced INH activation
      compared with the wild-type strain. Expression of MDP1 was increased in the
      stationary phase and conferred growth phase-dependent tolerance to INH in M.
      smegmatis. Regulation of KatG expression is conserved between M. smegmatis and
      Mycobacterium tuberculosis complex. Artificial reduction of MDP1 in Mycobacterium
      bovis BCG was shown to lead to increased KatG expression and susceptibility to
      INH. These data suggest a mechanism by which phenotypic tolerance to INH is
      acquired in mycobacteria.

PMID- 22648415
TI  - Spatial coordination of kindlin-2 with talin head domain in interaction with
      integrin beta cytoplasmic tails.
AB  - Both talin head domain and kindlin-2 interact with integrin beta cytoplasmic
      tails, and they function in concert to induce integrin activation. Binding of
      talin head domain to beta cytoplasmic tails has been characterized extensively,
      but information on the interaction of kindin-2 with this integrin segment is
      limited. In this study, we systematically examine the interactions of kindlin-2
      with integrin beta tails. Kindlin-2 interacted well with beta(1) and beta(3)
      tails but poorly with the beta(2) cytoplasmic tail. This binding selectivity was
      determined by the non-conserved residues, primarily the three amino acids at the
      extreme C terminus of the beta(3) tail, and the sequence in beta(2) was non
      permissive. The region at the C termini of integrin beta(1) and beta(3) tails
      recognized by kindlin-2 was a binding core of 12 amino acids. Kindlin-2 and talin
      head do not interact with one another but can bind simultaneously to the integrin
      beta(3) tail without enhancing or inhibiting the interaction of the other binding
      partner. Kindlin-2 itself failed to directly unclasp integrin alpha/beta tail
      complex, indicating that kindlin-2 must cooperate with talin to support the
      integrin activation mechanism.

PMID- 22648417
TI  - Structural factors that determine selectivity of a high fidelity DNA polymerase
      for deoxy-, dideoxy-, and ribonucleotides.
AB  - In addition to discriminating against base pair mismatches, DNA polymerases
      exhibit a high degree of selectivity for deoxyribonucleotides over ribo- or
      dideoxynucleotides. It has been proposed that a single active site residue
      (steric gate) blocks productive binding of nucleotides containing 2'-hydroxyls.
      Although this steric gate plays a role in sugar moiety discrimination, its
      interactions do not account fully for the observed behavior of mutants. Here we
      present 10 high resolution crystal structures and enzyme kinetic analyses of
      Bacillus DNA polymerase I large fragment variants complexed with deoxy-, ribo-,
      and dideoxynucleotides and a DNA substrate. Taken together, these data present a
      more nuanced and general mechanism for nucleotide discrimination in which
      ensembles of intermediate conformations in the active site trap non-cognate
      substrates. It is known that the active site O-helix transitions from an open
      state in the absence of nucleotide substrates to a ternary complex closed state
      in which the reactive groups are aligned for catalysis. Substrate misalignment in
      the closed state plays a fundamental part in preventing non-cognate nucleotide
      misincorpation. The structures presented here show that additional O-helix
      conformations intermediate between the open and closed state extremes create an
      ensemble of binding sites that trap and misalign non-cognate nucleotides. Water
      mediated interactions, absent in the fully closed state, play an important role
      in formation of these binding sites and can be remodeled to accommodate different
      non-cognate substrates. This mechanism may extend also to base pair
      discrimination.

PMID- 22648416
TI  - Nickel-induced epithelial-mesenchymal transition by reactive oxygen species
      generation and E-cadherin promoter hypermethylation.
AB  - Epithelial-mesenchymal transition (EMT) is considered a critical event in the
      pathogenesis of lung fibrosis and tumor metastasis. During EMT, the expression of
      differentiation markers switches from cell-cell junction proteins such as E
      cadherin to mesenchymal markers such as fibronectin. Although nickel-containing
      compounds have been shown to be associated with lung carcinogenesis, the role of
      nickel in the EMT process in bronchial epithelial cells is not clear. The aim of
      this study was to examine whether nickel contributes to EMT in human bronchial
      epithelial cells. We also attempted to clarify the mechanisms involved in NiCl(2)
      induced EMT. Our results showed that NiCl(2) induced EMT phenotype marker
      alterations such as up-regulation of fibronectin and down-regulation of E
      cadherin. In addition, the potent antioxidant N-acetylcysteine blocked EMT and
      expression of HIF-1alpha induced by NiCl(2), whereas the DNA methyltransferase
      inhibitor 5-aza-2'-deoxycytidine restored the down-regulation of E-cadherin
      induced by NiCl(2). Promoter hypermethylation of E-cadherin, determined by
      quantitative real time methyl-specific PCR and bisulfate sequencing, was also
      induced by NiCl(2). These results shed new light on the contribution of NiCl(2)
      to carcinogenesis. Specifically, NiCl(2) induces down-regulation of E-cadherin by
      reactive oxygen species generation and promoter hypermethylation. This study
      demonstrates for the first time that nickel induces EMT in bronchial epithelial
      cells.

PMID- 22648418
TI  - Conjugation of glutathione to oxidized tyrosine residues in peptides and
      proteins.
AB  - Tyrosine residues are sensitive to oxidation and can be converted to
      hydroperoxides either by superoxide reacting with the Tyr radical or by singlet
      oxygen. These hydroperoxides rearrange to bicyclic derivatives that are readily
      reduced to more stable hydroxides. The aromatic character of tyrosine is lost,
      but the product contains an alpha-beta unsaturated carbonyl group and is,
      therefore, an electrophile. We have generated hydroxide derivatives of several
      Tyr-containing peptides and shown using liquid chromatography/mass spectrometry
      that they undergo Michael addition with GSH. For Tyr-Gly, rate constants of 9.2
      and 11.8 m(-1)min(-1) were measured for the two chromatographically distinct
      isomers. Unusual for GSH addition to an electrophile, the reaction is reversible,
      with a half-life of many hours for the reverse reaction. These kinetics indicate
      that with a typical cellular concentration of 5 mm GSH, >95% Tyr-Gly hydroxide
      would become conjugated with a half-life of ~15 min. Sperm whale myoglobin forms
      a hydroperoxide on Tyr-151 in a hydrogen peroxide/superoxide-dependent reaction.
      We show that its hydroxide derivative reacts with GSH to form a conjugate.
      Detection of the conjugate required stabilization by reduction; otherwise, the
      reverse reaction occurred during tryptic digestion and analysis. Our findings
      represent a novel mechanism for peptide or protein glutathionylation involving a
      carbon-sulfur cross-link between oxidized Tyr and Cys. As with other
      electrophiles, the oxidized Tyr should undergo a similar reaction with Cys
      residues in proteins to give intramolecular or intermolecular protein cross
      links. This mechanism could give rise to protein cross-linking in conditions of
      oxidative stress.

PMID- 22648422
TI  - Hand and wrist imaging.

PMID- 22648419
TI  - Functional partnership of the copper export machinery and glutathione balance in
      human cells.
AB  - Cells use the redox properties of copper in numerous physiologic processes,
      including antioxidant defense, neurotransmitter biosynthesis, and angiogenesis.
      Copper delivery to the secretory pathway is an essential step in copper
      utilization and homeostatic maintenance. We demonstrate that the
      glutathione/glutathione disulfide (GSH/GSSG) pair controls the copper transport
      pathway by regulating the redox state of a copper chaperone Atox1. GSSG oxidizes
      copper-coordinating cysteines of Atox1 with the formation of an intramolecular
      disulfide. GSH alone is sufficient to reduce the disulfide, restoring the ability
      of Atox1 to bind copper; glutaredoxin 1 facilitates this reaction when GSH is
      low. In cells, high GSH both reduces Atox1 and is required for cell viability in
      the absence of Atox1. In turn, Atox1, which has a redox potential similar to that
      of glutaredoxin, becomes essential for cell survival when GSH levels decrease.
      Atox1(+/+) cells resist short term glutathione depletion, whereas Atox1(-/-)
      cells under the same conditions are not viable. We conclude that GSH balance and
      copper homeostasis are functionally linked and jointly maintain conditions for
      copper secretion and cell proliferation.

PMID- 22648420
TI  - Development and bioactivity evaluation of bioglasses with low Na2O content based
      on the system Na 2O-CaO-MgO-P 2O 5-SiO 2.
AB  - Osteoconductive bioglasses, free of K(2)O and Al(2)O(3) and with content of
      Na(2)O lower than 10 mol%, were designed based on the ratio (SiO(2) +
      MgO)/(P(2)O(5) + CaO + Na(2)O) in the system Na(2)O-CaO-MgO-P(2)O(5)-SiO(2). The
      developed glasses have shown a strong potential for the formation of
      hydroxycarbonated apatite (HCA) in vitro. The particles of HCA aggregates tend to
      be of finer size with increasing the ratio of (SiO(2) + MgO)/(CaO + P(2)O(5) +
      Na(2)O) in the glass chemical composition indicating significant bioactivity.
      Critical size bone defects created in the femurs of albino adult female rats, and
      grafted with the glass particles for 12 weeks post implantation, were completely
      healed by filling with mineralized bone matrix without infection showing a strong
      potential for new bone formation in vivo. Osteoblasts and osteocytes were
      observed close to the surface of the granular implants with active areas of bone
      deposition, resorption and remodelling. The bioglass with lowest (SiO(2) +
      MgO)/(CaO + P(2)O(5) + Na(2)O) ratio has shown the highest bioactivity while the
      bioglass with the highest (SiO(2) + MgO)/(CaO + P(2)O(5) + Na(2)O) has shown the
      lowest bioactivity. The newly formed bone in vivo has shown a similar structure
      to that of the original bone as indicated by the histology and microstructural
      results. In addition, Ca/P molar ratio of the newly formed bone was found to be
      (~1.67), which is similar to that of the original bone.

PMID- 22648423
TI  - Cartilage imaging of the hand and wrist using 3-T MRI.
AB  - The prevalence of osteoarthritis of the hand and wrist is high, and a thorough
      assessment of even subtle cartilage injuries is necessary before surgical
      interventions. Although magnetic resonance imaging (MRI) has been established as
      an important diagnostic tool for the evaluation of hand and wrist disorders, the
      focus has been on the assessment of the triangular fibrocartilage complex,
      tendons, ligaments, and the detection of avascular necrosis or occult fractures
      rather than on cartilage imaging. 3-T MR systems have become more and more widely
      available and yield an improved signal-to-noise ratio and thus a higher spatial
      resolution than 1.5-T systems. In principle, this should be especially beneficial
      for depicting the thin cartilage layers of the hand and wrist. This review
      focuses on cartilage imaging of the hand and wrist with 3-T MRI and addresses
      these four topics: (1) the advantages of 3-T versus 1.5- and 1-T MRI, (2)
      dedicated sequence protocols at 3 T including novel three-dimensional sequences,
      (3) imaging findings in common cases of overuse or sports injury, and (4)
      functional cartilage imaging techniques of the hand and wrist, for instance,
      delayed gadolinium-enhanced MRI of the cartilage.

PMID- 22648424
TI  - 7T imaging of the wrist.
AB  - Ultra-high-field magnetic resonance (MR) imaging provides a high signal-to-noise
      ratio and thus is expected to be superior to 1.5T and 3T MR systems that are
      currently used in daily routine. For use in the musculoskeletal system,
      expectations are high, particularly for smaller joints such as the wrist, because
      of the small size of the visualized anatomical structures, where high spatial
      resolution imaging is mandatory. However, there are technical challenges
      associated with ultra-high-field MR, and much of the necessary basic research has
      been done. This article reviews the literature of the past 10 years of research
      in this field, which reveals a promising pattern of continuing improvements and
      further developments. For this reason, it is likely that, in the near future,
      studies with larger study populations and more clinically driven research
      questions will follow.

PMID- 22648425
TI  - Anatomy and variants of the triangular fibrocartilage complex and its MR
      appearance at 3 and 7T.
AB  - Due to the small size and complexity of its constituents, the triangular
      fibrocartilage complex (TFCC) has been a challenging structure for magnetic
      resonance (MR) imaging. Higher-field MR units, at 3T and 7T, with increased
      spatial resolution and the development of novel MR sequences, are promising tools
      for an improved visualization of the ulnocarpal complex. Anatomically, the TFCC
      consists of the TFC proper, the ulnomeniscal homolog, the ulnar collateral
      ligament, the ulnotriquetral and ulnolunate ligament, and radioulnar ligaments at
      the volar (palmar) and the dorsal side, as well as the sheath of the extensor
      carpi ulnaris tendon and the capsule of the distal radioulnar joint. This article
      describes the normal anatomy of the TFCC and its appearance on high-field MRI.
      Anatomical variants, such as the positive ulnar variance, and changes during
      pronation and supination are addressed.

PMID- 22648426
TI  - Normal anatomy of the extrinsic capsular wrist ligaments by 3-T MRI and high
      resolution ultrasonography.
AB  - The anatomy of the extrinsic capsular wrist ligaments is complex. These ligaments
      are probably as important as the intrinsic interosseous ligaments for the
      maintenance of carpal stability. The extrinsic capsular wrist ligaments are
      frequently divided into dorsal, palmar, and collateral depending on their
      anatomical location. They have known origin and attachment sites with recognized
      anatomical variants. However, there is controversy in the literature related to
      their anatomy and nomenclature. In the past two decades, imaging has gained an
      important role in the evaluation of the extrinsic capsular wrist ligaments. Both
      1.5-T magnetic resonance imaging (MRI) and magnetic resonance arthrography can
      provide good evaluation of the extrinsic capsular wrist ligaments; 3-T MRI with
      improved resolution provides better visualization of the same anatomical
      structures. Ultrasonography using high-resolution linear transducers allows good
      visualization of the extrinsic capsular wrist ligaments with results that are
      comparable with MRI. This article describes the normal anatomy of the dorsal,
      palmar, and collateral extrinsic capsular wrist ligaments on 3-T MRI and high
      resolution ultrasonography.

PMID- 22648427
TI  - Pathology of extrinsic ligaments: a pictorial essay.
AB  - The role of the extrinsic ligaments, together with the intrinsic ligaments,
      appears to be much more important than previously thought in the setting of
      carpal stability. The anatomy and pathology of the extrinsic wrist ligaments is
      complex. Magnetic resonance imaging (MRI) with thin slices is essential for
      visualization. This article describes the pathological appearance of the
      extrinsic palmar and dorsal radiocarpal and ulnocarpal ligaments on MRI,
      correlated with arthroscopy (performed by two skilled hand surgeons), clinical
      findings, and follow-up. High-resolution MRI, especially using isotropic three
      dimensional sequences with orthogonal multiplanar reconstructions on 3T MR
      systems, allows detailed depiction of many of the extrinsic ligaments affected in
      carpal injuries. Recognition of ligament abnormalities is improved by intra
      articular or intravenous injection of contrast before the examination. Both
      techniques may help to determine the precise localization, size, and extent of
      dorsal and palmar radiocarpal and ulnocarpal ligament lesions. Further experience
      with these techniques is needed to define the place of MRI in the management of
      traumatic wrist injuries.

PMID- 22648428
TI  - Nerves of the hand beyond the carpal tunnel.
AB  - Imaging studies including ultrasound (US) and magnetic resonance imaging may be
      required to evaluate the median nerve in patients with suspected carpal tunnel
      syndrome. However, the radial and ulnar nerves contribute to sensory and motor
      innervations to the hand as well. Compressive, traumatic, and iatrogenic events
      may damage the small terminal branches of these nerves. In the hand, US is able
      to identify injuries of the median, ulnar, radial nerve, and terminal branches.
      This article presents the role of imaging to evaluate the nerves of the hand with
      an emphasis on US. Due to its high-resolution capabilities, US is useful to
      determine the location, extent, and type of nerve lesion. Moreover, US is useful
      for a postsurgical assessment. The anterior interosseous nerve, Guyon's tunnel
      syndrome, and Wartenberg's syndrome are also described.

PMID- 22648429
TI  - Imaging of the carpal tunnel.
AB  - Most patients with symptoms related to the carpal tunnel have idiopathic median
      nerve compression. Imaging has little role in the care of most cases because
      steroid injection, therapeutic ultrasound, and surgery have established roles.
      However, cases with atypical presentation, mass lesions, synovitis, or failed
      carpal tunnel surgery will benefit from imaging. In this article we review the
      anatomy of the carpal tunnel, the diseases affecting this region, and then
      discuss the use of conventional radiographs, computed tomography, ultrasound, and
      magnetic resonance imaging (MRI), outlining the strengths and weaknesses of each
      method while listing the signs of disease. We conclude that both ultrasound
      examination and MRI are powerful and often complementary techniques.

PMID- 22648430
TI  - Congenital malformations of the hand and forearm in children: what radiologists
      should know.
AB  - Congenital upper limb malformations represent complex pathologies because of
      their varied clinical presentations, imaging features, and etiologies. They can
      be divided into (1) failure of formation with transverse, intercalary, and
      longitudinal (preaxial, postaxial, and mesoaxial) deficiencies, (2) failure of
      differentiation with synostoses, carpal coalitions, syndactylies, and
      symphalangism, (3) duplication with ulnar dimelia and polydactylies, and (4)
      brachydactylies. Congenital Madelung's deformity, clinodactyly, camptodactyly,
      and Kirner's deformity are usually included in these malformations. Despite
      advances in molecular diagnosis, a good knowledge of clinical and imaging
      features as well as special consideration of other skeletal or nonskeletal
      abnormalities are essential to eventually diagnose an embryo fetopathy (maternal
      valproate treatment, constriction band syndrome), a genetic disorder (trisomy 21
      or Down syndrome, Turner's syndrome, Holt-Oram syndrome), or a nongenetic
      syndrome (vertebral, anal, cardiac, tracheal, esophageal, renal, limb
      association, Poland's syndrome). Genetic counseling for a child presenting with a
      congenital upper limb malformation is of great value, both for the treating team
      and the parents, and imaging is often required. The latter is still largely
      supported by conventional radiography, both for diagnosis and functional
      prognosis, but ultrasound and magnetic resonance imaging will be great tools in
      the near future to better evaluate these conditions.

PMID- 22648431
TI  - Imaging and treatment of scaphoid fractures and their complications.
AB  - The scaphoid is the most commonly fractured carpal bone, with frequent
      complications that are predisposed by its anatomical location, anatomical
      configuration (shape and length), and vascular supply. The most common mechanism
      of injury is a fall onto an outstretched hand. Imaging plays a significant role
      in the initial evaluation and treatment of scaphoid fractures and their
      complications. Radiography should be the first imaging modality in the initial
      evaluation and follow-up of scaphoid fractures. Computed tomography with its
      superb spatial resolution enables better visualization and characterization of
      the fracture line, and the amount of displacement and angulation of the fracture
      fragments. Using the metal reduction artifact with computed tomography allows
      good follow-up of scaphoid fractures despite surgical hardware. Magnetic
      resonance imaging without contrast is the imaging modality of choice for
      depiction of radiographically occult scaphoid fracture, bone contusion, and
      associated soft tissue injury; contrast-enhanced imaging aids assessment of
      scaphoid fracture nonunion, osteonecrosis, fracture healing after bone grafting,
      and revitalization of the necrotic bone after bone grafting. Proper
      identification and classification of scaphoid fracture and its complications is
      necessary for appropriate treatment. This article describes the normal anatomy,
      mechanism of injury, and classification of stable and unstable fractures,
      together with the imaging and treatment algorithm of scaphoid fractures and their
      complications with an emphasis on magnetic resonance imaging.

PMID- 22648433
TI  - Patient experience in outpatient pediatric otolaryngology.
AB  - OBJECTIVES/HYPOTHESIS: Patient experience scores are emerging as a key measure of
      healthcare quality. This report evaluated differences in outpatient
      otolaryngology patient satisfaction scores by age. STUDY DESIGN: Patient-level
      analysis of Press Ganey Medical Practice surveys completed by otolaryngology
      patients or parents in 2010. METHODS: Surveys were grouped by child (<18 years
      old) or adult age. Children were evaluated in three subgroups (0-5 years, 6-12
      years, and 13-17 years). The survey contains 29 items, which comprise six service
      domains of access, visit, nursing, provider, personal issues, and assessment.
      Comparison of mean scores was performed using the Kruskal-Wallis rank test for
      nonparametric data. Multivariate logistic regression analysis was performed to
      evaluate association of age with receipt of highest scores (HI-SCORES) in each
      domain. RESULTS: Of 44,010 surveys analyzed, 5,996 (13.6%) were pediatric. The
      majority of children were <6 years (n = 3,141; 52.4%). Mean scores were lower for
      children overall (88.4 children vs. 90.2 adults) and in domains of access, visit,
      nursing, issues, and assessment (P < .005, all comparisons); scores were equal
      for care provider. Mean scores were lowest for children 0 to 5 years across all
      domains (overall means: 88.0, 0-5; 88.4, 6-12; 89.4, 13-17; 90.2 >18; P = .0001)
      and increased with age. Multivariate analysis showed that children were less
      likely than adults to give HI-SCORES overall (odds ratio, 0.81, 95% confidence
      interval, 0.76-0.86; P < .001) and in all domains (P = .0001) except for
      provider. CONCLUSIONS: Compared to adults, satisfaction is lower in all service
      domains except care provider for pediatric otolaryngology patients, and is lowest
      for younger children. Otolaryngologists should consider the unique needs of the
      child and family to improve overall patient experience.

PMID- 22648435
TI  - Extended RET gene analysis in patients with apparently sporadic medullary thyroid
      cancer: clinical benefits and cost.
AB  - RET sequencing has become an important tool in medullary thyroid cancer (MTC)
      evaluation and should be performed even in the absence of family history of MTC.
      The most commonly studied exons in index cases are 8, 10, 11, and 13-16. To
      address the ATA guidelines regarding the sequencing of the entire coding region
      of RET, we selected 50 patients with sporadic MTC (sMTC) without mutations in the
      hot spot regions of RET for extended investigation of exons 1-7, 9, 12, 17, 18,
      and 19. Twenty-seven of 50 patients presented with one or more features
      suggesting familial disease. We found only a new RET variant (p.Gly550Glu) in one
      patient with MTC. Several polymorphisms were observed, and their frequency was
      histogram scaled by exons and introns. Eight patients were also included for
      somatic mutation search. We estimated the sequencing cost by stratifying into
      four investigation approaches: (1) hot spot exons in a new patient, (2) the
      remaining exons if the hot spots are negative in a patient with suspected
      familial disease, (3) a relative of a carrier for a known RET mutation, and (4)
      tumor sequencing. In spite of the increasing number of variants being described
      in MTC, it appears that there is no direct clinical benefit in extending RET germ
      line analysis beyond the hot spot regions in sMTC. The cost evaluation in
      apparent sMTC using a tiered approach may help clinicians make more suitable
      decisions regarding the benefits of investigating only the hot spots against the
      entire coding region of RET.

PMID- 22648436
TI  - Dexrazoxane does not affect treatment outcome in non-Hodgkin's lymphoma patients.

PMID- 22648443
TI  - Effect of mifepristone on COX-2 both in eutopic and ectopic endometrium in mouse
      endometriotic model.
AB  - OBJECTIVE: To study the influence of mifepristone on the expression of
      cyclooxygenase 2 (COX-2) protein and COX-2 mRNA and then to evaluate the
      mechanism. METHODS: After the establishment of 30 mice endometriosis models, the
      mice were randomly divided into six groups with 5 mice each group and assigned to
      experimental and control groups of 1-, 4- and 6-week circle according to whether
      mifepristone (0.13 mg d(-1)) was taken or not. Small animal optical imaging
      system was used to detect the fluorescent intensity of the ectopic tissue.
      Reverse transcript-polymerase chain reaction and western blot was used to examine
      COX-2 protein and COX-2 mRNA expression. ELISA was used to examine concentration
      of PGE(2) in serum. RESULT(S): Mifepristone could not affect the fluorescent
      intensity of the ectopic endometrium after it was taken 1, 4, and 6 (P > 0.05).
      However, it could decrease the transcription of COX-2 mRNA in the 1 and 4 week
      groups (P < 0.05), while the difference in the 6 week group was not significant
      (P > 0.05). It could decrease the expression of COX-2 protein after it was taken
      4 and 6 weeks (P < 0.05). The serous PGE(2) in the trial groups was lower than
      that in the control groups, but the difference was not significant (P > 0.05).
      CONCLUSION(S): This study showed that mifepristone could not affect the size of
      the ectopic endometrium, but it could decrease the transcription of COX-2 gene
      and then reduce the expression of COX-2 protein and its product PGE(2) which is
      an important factor which mediate pain. This maybe another mechanism that
      mifepristone takes effect through anti-inflammatory path.

PMID- 22648437
TI  - Risk factors for metabolic syndrome independently predict arterial stiffness and
      endothelial dysfunction in patients with chronic kidney disease and minimal
      comorbidity.
AB  - OBJECTIVE: Metabolic syndrome (MS) is common in patients with chronic kidney
      disease (CKD), but its contribution to arterial stiffness and endothelial
      dysfunction in CKD is not well defined. We hypothesized that risk factors for MS
      would independently predict arterial stiffness and endothelial dysfunction in CKD
      patients. RESEARCH DESIGN AND METHODS: Risk factors for MS, carotid-femoral pulse
      wave velocity (CF-PWV) and flow-mediated dilation (FMD) as measures of arterial
      stiffness and endothelial dysfunction, respectively, were assessed in 113
      minimally comorbid CKD patients and in 23 matched control subjects. RESULTS: CF
      PWV correlated with systolic blood pressure (SBP), waist circumference, and
      plasma glucose (r(2) = 0.25, 0.09, and 0.09; P < 0.01 for all). FMD correlated
      with SBP (r(2) = 0.09; P < 0.01) and waist circumference (r(2) = 0.03; P < 0.05).
      CF-PWV increased progressively (r(2) = 0.07; P < 0.01) with increasing number of
      risk factors for MS. In multiple linear regression, SBP and waist circumference
      were independent determinants of CF-PWV, whereas only SBP predicted FMD.
      CONCLUSIONS: The number of MS risk factors is an important determinant of
      arterial stiffness in CKD patients irrespective of the degree of renal
      impairment. Although BP remains the major determinant of arterial stiffness and
      endothelial dysfunction, waist circumference independently predicts arterial
      stiffness. MS risk factors, particularly abdominal girth, are potential targets
      for future interventional studies in patients with CKD.

PMID- 22648444
TI  - Skin adhesive low-level light therapy for dysmenorrhoea: a randomized, double
      blind, placebo-controlled, pilot trial.
AB  - PURPOSE: The cause of dysmenorrhoea is an abnormal function of smooth muscles in
      the uterus due to long-term deficient blood supply into smooth muscle tissue. The
      purpose of this study was to evaluate the effectiveness of skin adhesive low
      level light therapy (LLLT) in participants with dysmenorrhoea. METHODS: Thirty
      one women were included in this randomized, double-blind, placebo-controlled,
      pilot trial. Twenty-one women were treated with active LLLT and ten women were
      treated with placebo one. The therapy was performed in a laboratory room for 20
      min a day over a period of 5 days prior to the expected onset of menstruation.
      The outcome was measured using a visual analog scale (VAS) for each participant's
      dysmenorrhoeal pain severity. VAS of each subject was measured every month for 6
      months. RESULTS: In the active LLLT group, 16 women reported successful results
      during their first menstrual cycle just after active LLLT and 5 women had
      successful results from the second menstrual cycle after active LLLT. The pain
      reduction rate was 83 % in the active LLLT group, whereas there was only a slight
      and temporary reduction in pain in the placebo LLLT group. Changes of VAS within
      6 months of LLLT showed statistical significance (p = 0.001) over placebo
      control. CONCLUSIONS: Our study suggests that skin adhesive LLLT on acupuncture
      points might be an effective, simple and safe non-pharmacological treatment for
      dysmenorrhoea.

PMID- 22648445
TI  - Anterior colporrhaphy versus repair with mesh for anterior vaginal wall prolapse:
      a comparative clinical study.
AB  - PURPOSE: To compare the clinical effectiveness of anterior colporrhaphy versus
      mesh repair as surgical management of anterior vaginal prolapse. METHODS: Of 50
      patients with >=stage II anterior vaginal prolapse on Pelvic Organ Prolapse
      Quantification (POPQ) system who were initially approached, 44 consented and
      underwent surgery. They were randomly recruited into two groups. Group I (23
      patients) received anterior colporrhaphy, while group II (21 patients) received
      soft polypropylene mesh (GYNEMESH*PS, Gynecare, Ethicon, France). Clinical
      assessment took place preoperatively and postoperatively at definite intervals.
      Functional and anatomical comparisons were based on comparison between
      preoperative and 24 months postoperative assessments of symptoms and POPQ stages,
      respectively. Four patients in total did not complete the follow-up assessments
      and were excluded. RESULTS: Both groups showed clinical improvement in their
      symptoms and POPQ staging at the end of the postoperative follow-up period.
      Improvement, however, was more significant in the repair with mesh group, as
      patients in this group reported better improvement of their prolapse symptoms,
      mainly vaginal bulge/pressure sensation (P < 0.05), and showed better improvement
      in the anatomical staging, individual POP-Q points Aa and Ba (P < 0.01), than the
      anterior colporrhaphy group. Group II also showed more satisfactory outcome with
      the general POP-Q staging (P < 0.05) than group I, reflecting a better quality of
      life of the patients in the repair with mesh group. CONCLUSION: Our data shows
      that repair with mesh is superior to anterior colporrhaphy with more satisfactory
      outcome to the patients. Due to the small size of our study and uncertainty of
      the long-term safety and resilience of the mesh, we recommend larger studies to
      confirm our preliminary results.

PMID- 22648446
TI  - Therapeutic efficiency of Atosiban, an oxytocin receptor blocking agent in the
      treatment of experimental endometriosis.
AB  - PURPOSE: The current study investigated the potential therapeutic efficiency of
      atosiban, an oxytocin receptor antagonist, in an experimental endometriosis
      model. METHODS: Endometriosis was surgically induced in 35 female rats during
      estrus. Four weeks after this procedure, relaparotomy was performed. The
      viability and dimensions of the endometriosis foci were recorded. Rats were then
      randomly divided into three groups. In the first group (n = 8), a daily dose of
      0.2 ml 0.9 % NaCl was injected intraperitoneally (i.p.) (control cases). In the
      second and third groups (n = 8 and n = 8), 0.5 mg/kg/day i.p. atosiban and 1
      mg/day i.p. diltiazem were given, respectively. At the end of the treatment,
      laparotomy was performed, and the dimensions of the endometriosis foci were
      recorded. The endometrial implants were processed for histological and
      immunohistochemical studies. The volumes of endometriotic implants were measured,
      and immunohistochemical analyses were performed, and compared between the groups.
      RESULTS: After the treatment with atosiban, volumes of endometriotic implants
      decreased significantly. Proliferating cell nuclear antigen expression levels
      were significantly reduced in the atosiban and diltiazem groups compared with the
      control group. CONCLUSIONS: In a rat endometriosis model, atosiban, an agent used
      for the first time for the medical treatment of endometriosis, has shown
      significant therapeutic efficiency.

PMID- 22648447
TI  - Implementation of laparoscopic sacrocolpopexy: establishment of a learning curve
      and short-term outcomes.
AB  - PURPOSE: To evaluate the learning curve of senior urogynecologic surgeons
      performing laparoscopic sacral colpopexy (LSCP) and to assess outcomes and
      complications of LSCP. METHODS: We conducted a retrospective study of 47
      consecutive women who underwent LSCP for pelvic organ prolapse repair between
      March 2009 and December 2010 at one tertiary medical center. Preoperative,
      intraoperative, postoperative, and demographic data were retrieved from patients'
      electronic charts. Pelvic organ support was assessed objectively using the Pelvic
      Organ Prolapse Quantification scale (POP-Q). Anatomic failure was determined as
      POP-Q stage >= II. RESULTS: The mean age of patients was 58 years (range 35-73
      years). Seven (15 %) who opted to retain their uterus underwent
      sacrohysteropexies. The median POP-Q was III (II-IV). Of the 47 operations, 96 %
      (45) were completed by laparoscopy. The duration of surgery decreased as
      experience of the surgical team increased, from a mean of 196 +/- 62 min for the
      first 15 cases to 162 +/- 30 min for the subsequent 30. Four patients (9 %)
      presented with recurrence of prolapse; three (7 %) had de novo stress urinary
      incontinence; two sustained a cystotomy during adhesiolysis, and one had a port
      site hernia. CONCLUSIONS: LSCP is a safe and effective treatment for pelvic organ
      prolapse, with very few complications. Following the first 15 cases of one
      surgical team, operative time decreased considerably.

PMID- 22648448
TI  - A novel approach to postoperative bladder care in women after radical
      hysterectomy.
AB  - PURPOSE: Currently, controversy exists with regard to the duration of bladder
      drainage and choice of catheter used in women who undergo radical hysterectomy.
      In this manuscript, we propose a novel approach to improving postoperative
      bladder care in women who undergo radical hysterectomy. METHODS: This is a
      retrospective study of women who underwent Type 3 Piver radical hysterectomy in a
      gynaecological oncology centre in the United Kingdom from January 2009 to
      September 2011. We report the outcomes of removal of urinary catheter 48-72 h
      following radical hysterectomy. RESULTS: Over a 32-month period, 30 women
      underwent radical hysterectomy. 19 (63.3 %) women underwent surgery for treatment
      of cervical cancer, 5 (16.7 %) women for management of endometrial cancer, 6 (20
      %) women for other conditions. One patient underwent partial cystectomy at the
      time of radical hysterectomy and was not included in the analysis. Of the 29
      patients, only five (17.2 %) were found to have urinary residuals greater than
      100 ml following the removal of the indwelling catheter on the second
      postoperative day and required recatheterisation. 82.8 % of the patients had the
      catheter removed within 48-72 h postoperatively. None of these patients required
      re-admission with urinary retention. CONCLUSION: Removal of urinary catheter on
      the second postoperative day following radical hysterectomy is feasible and not
      associated with increased morbidity. This approach may be particularly useful to
      complement the introduction of laparoscopic and robotic surgical approaches for
      surgical management of cervical cancer.

PMID- 22648449
TI  - Anti-CD47 antibodies promote phagocytosis and inhibit the growth of human myeloma
      cells.
AB  - Multiple myeloma is a plasma cell neoplasm residing in bone marrow. Despite
      advances in myeloma therapies, novel therapies are required to improve patient
      outcomes. CD47 is highly expressed on myeloma cells and a potential therapeutic
      candidate for myeloma therapies. Flow cytometric analysis of patient bone marrow
      cells revealed that myeloma cells overexpress CD47 when compared with non-myeloma
      cells in 73% of patients (27/37). CD47 expression protects cells from
      phagocytosis by transmitting an inhibitory signal to macrophages. Here we show
      that blocking CD47 with an anti-CD47 monoclonal antibody increased phagocytosis
      of myeloma cells in vitro. In xenotransplantation models, anti-CD47 antibodies
      inhibited the growth of RPMI 8226 myeloma cells and led to tumor regression
      (42/57 mice), implicating the eradication of myeloma-initiating cells. Moreover,
      anti-CD47 antibodies retarded the growth of patient myeloma cells and alleviated
      bone resorption in human bone-bearing mice. Irradiation of mice before myeloma
      cell xenotransplantation abolished the therapeutic efficacy of anti-CD47
      antibodies delivered 2 weeks after radiation, and coincided with a reduction of
      myelomonocytic cells in spleen, bone marrow and liver. These results are
      consistent with the hypothesis that anti-CD47 blocking antibodies inhibit myeloma
      growth, in part, by increasing phagocytosis of myeloma cells.

PMID- 22648450
TI  - Sonographic guidance provides a low-risk approach to the longus colli muscle.

PMID- 22648453
TI  - Efficient phosphorescent polymer light-emitting diodes by suppressing triplet
      energy back transfer.
AB  - Phosphorescent polymer light-emitting diodes (PhPLEDs) are promising devices in
      flat panel displays and solid state lighting sources since they can combine the
      advantages of the high efficiency of electrophosphorescence and low-cost, large
      scale manufacture by using a solution process. However, their efficiencies are
      generally much lower than those of small-molecule-based devices fabricated by
      using a thermal deposition approach. One of the major reasons for their low
      efficiency is that energy is lost by back transfer to a polymer host. This
      tutorial review gives a brief introduction to the fundamentals of PhPLEDs, and
      then highlights recent progress in the main approaches to suppress triplet energy
      back transfer from the phosphor to the polymer host towards realizing highly
      efficient PhPLEDs. The suppressing mechanisms are discussed, and the achievement
      of high device efficiencies are demonstrated. Emphasis is placed on the
      relationships between molecular structure, the extent of suppressing triplet
      energy back transfer, and device performance.

PMID- 22648452
TI  - Developing a mobile produce distribution system for low-income urban residents in
      food deserts.
AB  - Low-income households in the contemporary city often lack adequate access to
      healthy foods, like fresh produce, due to a variety of social and spatial
      barriers that result in neighborhoods being underserved by full-service
      supermarkets. Because of this, residents commonly resort to purchasing food at
      fast food restaurants or convenience stores with poor selections of produce.
      Research has shown that maintaining a healthy diet contributes to disease
      prevention and overall quality of life. This research seeks to increase low
      income residents' access to healthy foods by addressing spatial constraints
      through the characterization of a mobile market distribution system model that
      serves in-need neighborhoods. The model optimally locates mobile markets based on
      the geographic distribution of these residents. Using data from the medium-sized
      city of Buffalo, New York, results show that, with relatively few resources, the
      model increases these residents' access to healthy foods, helping to create a
      healthier city.

PMID- 22648454
TI  - Comparative effectiveness and cost of adding rituximab to first-line chemotherapy
      for elderly patients diagnosed with diffuse large B-cell lymphoma.
AB  - BACKGROUND: Clinical trials indicate that rituximab improves the survival of
      patients with diffuse large B-cell lymphoma (DLBCL). Economic models using
      multiple data sources, including clinical trials for survival outcomes, have
      projected cost offsets/savings and favorable cost-effectiveness associated with
      rituximab. In this study, the authors evaluated survival and cost impacts of
      adding rituximab to first-line chemotherapy for DLBCL using a single database
      that reflects routine clinical practice among elderly patients in the United
      States. METHODS: By using Surveillance, Epidemiology, and End Results (SEER) data
      linked to Medicare, the authors identified 5484 elderly patients who were
      diagnosed with DLBCL between January 1999 and December 2005 who had claims
      through December 2007. Included patients began chemotherapy with or without
      rituximab within 180 days of diagnosis. Multivariate analyses were conducted to
      estimate the impact of rituximab on mortality and costs to Medicare. The cost per
      life-year gained of rituximab was calculated using cost and survival estimates
      from the multivariate analyses. RESULTS: The mean patient age was 76 years, 43%
      of patients had stage III or IV disease, and 64% received rituximab. In a Cox
      regression model, rituximab resulted in lower 4-year all-cause mortality (hazard
      ratio [HR], 0.68; 95% confidence interval [CI], 0.61-0.74) and cancer mortality,
      and the incremental cumulative survival was 0.37 years. In least-squares
      regression, rituximab resulted in higher 4-year total costs ($23,097; 95% CI,
      $19,129-$27,298), immunochemotherapy costs ($12,069; 95% CI, $10,687-$13,634),
      other cancer costs ($7655; 95% CI, $5067-$10,489), and noncancer costs ($3461;
      95% CI, $1319-$5650). The cost per life-year gained was $62,424. CONCLUSIONS: In
      routine clinical practice, rituximab was associated with survival benefits
      comparable to those observed in clinical trials. However, these benefits did not
      translate into the previously reported cost savings.

PMID- 22648455
TI  - The multiple autoimmune syndromes. A clue for the autoimmune tautology.
AB  - The multiple autoimmune syndromes (MAS) consist on the presence of three or more
      well-defined autoimmune diseases (ADs) in a single patient. The aim of this study
      was to analyze the clinical and genetic characteristics of a large series of
      patients with MAS. A cluster analysis and familial aggregation analysis of ADs
      was performed in 84 patients. A genome-wide microsatellite screen was performed
      in MAS families, and associated loci were investigated through the pedigree
      disequilibrium test. Systemic lupus erythematosus (SLE), autoimmune thyroid
      disease (AITD), and Sjogren's syndrome together were the most frequent ADs
      encountered. Three main clusters were established. Aggregation for type 1
      diabetes, AITD, SLE, and all ADs as a trait was found. Eight loci associated with
      MAS were observed harboring autoimmunity genes. The MAS represent the best
      example of polyautoimmunity as well as the effect of a single genotype on diverse
      phenotypes. Its study provides important clues to elucidate the common mechanisms
      of ADs (i.e., autoimmune tautology).

PMID- 22648456
TI  - [Chronic bullous disease of childhood. Long-term therapy over 8 years with 4,4'
      diaminodiphenylsulfone].
AB  - A 3-year-old boy presented with a generalized bullous disease, clinically
      strongly indicative of chronic bullous disease of childhood (CBDC). The diagnosis
      was confirmed by histopathology and further verified by several immunological and
      biochemical examinations. Direct immunofluorescence (IF) of perilesional skin
      revealed in vivo bound IgA-autoantibodies (aabs) in a linear pattern along the
      basement membrane zone; indirect IF revealed circulating IgA-aabs bound to the
      roof of "split skin" preparations of healthy human skin; immunoblotting of
      epidermal protein extracts showed that the aabs bound to a 97KD/120KD protein.
      Therapy with 4,4'-diaminodiphenylsulfone (DADPS, 2 mg/kg /daily), combined with
      prednisolone for the first month, was initiated, and promptly led to complete
      remission. Two attempts to stop DADPS treatment after 3 and 5 years of continuous
      therapy were followed by prompt recurrences. The boy is now 8 years old; with
      continuous DADPS therapy (1 mg/kg body weight/d), he displays regular physical
      and intellectual development.

PMID- 22648457
TI  - [Pruritus and psoriasis : an important but frequently underestimated relation].
AB  - Pruritus is a frequent but often unrecognized and underestimated symptom in
      patients with psoriasis. The underreporting may be due to lower frequency and
      reduced intensity of pruritus compared to other pruritic diseases such as atopic
      eczema or uremic pruritus, as well as impairment of psychosocial well-being
      caused by e.g. depression, social withdraw and secretiveness. Recent studies show
      pruritus being more prevalent in psoriasis, especially plaque-type psoriasis,
      than previously believed and severely affecting patients' quality of life. The
      assessment of pruritus and its associated effects is a significant component of
      clinical management of psoriasis. The presented suggest we should not
      underestimate pruritus in psoriasis and must consider this symptom in planning
      therapy.

PMID- 22648460
TI  - High intensity training for faster water polo.
AB  - AIM: The aim of this study, based on the interaction between two aerobic and
      anaerobic metabolisms with a parallel production of both aerobic and anaerobic
      ATP, was to develop a high intensity training programme and increase the aerobic
      contribution. We examined the applicability of a 16-week training programme with
      an ergospirometer treadmill and field tests on eight water polo players. METHODS:
      Tests/retests of repeated exercises to 90V (90% of maximum personal speed over
      100 m freestyle) and Speed Endurance Training (SET) after eight weeks were
      developed. A one-way blocked ANOVA with random blocks was used and each player
      represented a particular block with two before-after treatments with the aim of
      reducing error by subtracting both the variance due to the difference between the
      treatments and that due to the difference between the blocks. RESULTS: A
      reduction (15.2%) in blood lactate was observed in response to the same absolute
      workload (before-after). Furthermore the anaerobic contribution to VO2max
      (ESCAna, Estimated Anaerobic Contribution) after eight weeks of training at
      90maxV and the anaerobic contribution to VO2max (ESCAna) after speed endurance
      training (SET) were very significant (P<0.004) with a reduction in the anaerobic
      contribution of 16%. The results of the field tests show that there was a very
      significant reduction (P<0.001) in lactate between 90maxV and maximal aerobic
      power velocity (MAPv) of 24%. CONCLUSION: With 90maxV and SET, space was gained
      towards those velocities, which had previously required a considerable anaerobic
      contribution. In this way match speed was increased.

PMID- 22648459
TI  - Increased serum concentration of sphingosine-1-phosphate in juvenile-onset
      systemic lupus erythematosus.
AB  - PURPOSE: Sphingosine-1-phosphate (S1P) is an active sphingolipid with chemotactic
      abilities and has been linked to inflammatory mediators and autoimmune disease.
      The aim of this study was to assess whether children with juvenile-onset systemic
      lupus erythematosus (JSLE) express increased systemic and/or urinary
      concentrations of S1P. METHODS: A subgroup of patients participating in the UK
      JSLE Cohort Study, were invited to participate. Cross sectional serum and urine
      samples were prospectively collected along with demographic and standard clinical
      data. Results were compared to a cohort of disease controls (Henoch Schonlein
      Purpura; HSP) and healthy controls (HC). RESULTS: The median age of JSLE patients
      (n = 15) was 13.6 years (7.2-16.9 years). The serum concentrations of S1P in JSLE
      patients (7.4 uM, IQR 6.3-12.3 uM) were statistically significantly increased
      when compared to patients with HSP (n = 10; 5.2 uM, IQR 4.0-7.9 uM; p = 0.016)
      and HCs (n = 10; 3.8 uM, IQR 2.1-5.8 uM; p = 0.003). There was a trend towards
      increased serum S1P concentrations between patients with active lupus nephritis
      (n = 8; 8.7 uM, IQR 6.2-15.3 uM) compared to lupus non-nephritis (n = 7; 6.6 uM,
      IQR 6.3-10.6 uM; p = 0.355). No relationship was found between disease activity
      markers and S1P. Urine S1P concentrations were no different between JSLE patients
      (56.0 nM, IQR 40.3-96.6 nM) and HCs (58.7 nM, IQR 0-241.9 nM; p = 0.889).
      CONCLUSIONS: We have demonstrated, for the first time, an increased serum
      concentration of S1P in a cohort of JSLE patients. These findings highlight a
      role of S1P in the pathophysiology of JSLE that warrants further investigation.

PMID- 22648458
TI  - Acetylation of retinal histones in diabetes increases inflammatory proteins:
      effects of minocycline and manipulation of histone acetyltransferase (HAT) and
      histone deacetylase (HDAC).
AB  - Histone acetylation was significantly increased in retinas from diabetic rats,
      and this acetylation was inhibited in diabetics treated with minocycline, a drug
      known to inhibit early diabetic retinopathy in animals. Histone acetylation and
      expression of inflammatory proteins that have been implicated in the pathogenesis
      of diabetic retinopathy were increased likewise in cultured retinal Muller glia
      grown in a diabetes-like concentration of glucose. Both the acetylation and
      induction of the inflammatory proteins in elevated glucose levels were
      significantly inhibited by inhibitors of histone acetyltransferase (garcinol and
      antisense against the histone acetylase, p300) or activators of histone
      deacetylase (theophylline and resveratrol) and were increased by the histone
      deacetylase inhibitor, suberolylanilide hydroxamic acid. We conclude that
      hyperglycemia causes acetylation of retinal histones (and probably other
      proteins) and that the acetylation contributes to the hyperglycemia-induced up
      regulation of proinflammatory proteins and thereby to the development of diabetic
      retinopathy.

PMID- 22648461
TI  - Physiological response of high-level female judokas measured through laboratory
      and field tests. Retesting the validity of the Santos test.
AB  - AIM: The aim of the study was to measure the physiological demands of a group of
      high-level female judokas through laboratory tests and field tests (Tatami) and
      to retest the validity of the Santos test on a different population. METHODS:
      Eight high-level female judokas participated in the study. Heart rate (HR),
      maximal oxygen consumption (VO2 max), blood lactate, anaerobic threshold, and
      ratings of perceived exertion (RPE) were measured using laboratory and field
      tests that shared common characteristics. RESULTS: The mean (+/-SD) values
      obtained in the laboratory tests were HRmax 198.3 (4.1) beats.min-1, VO2 max:
      40.9 (7.7) mL.kg-1.min-1, lactate max 9.1 (1.4) mmol.L-1, HR at the anaerobic
      threshold 171.5 (4.8) beats.min-1, lactate threshold 3.8 (0.4) mmol.L-1, and RPE:
      17 (1.1). The mean (+/-SD) values obtained in the field test were HRmax 199.0
      (5.0) beats.min-1, VO2 max: 44.8 (7.3) mL.kg-1.min-1, lactate max: 11.8 (1.5)
      mmol.l-1, HR at the anaerobic threshold 170.5 (3.2) beats.min-1, lactate
      threshold: 3.8 (0.1) mmol.L-1, and RPE: 18 (1.4) points. There were no
      significant differences between the data obtained on both tests in any of the
      parameters, except for the lactate maximum and VO2 max. CONCLUSION: The Santos
      test is a helpful instrument for judo training in female athletes. Coaches could
      use it to design specific training protocols that could help to improve their
      performance in competition.

PMID- 22648462
TI  - Sport-specific fitness testing differentiates professional from amateur soccer
      players where VO2max and VO2 kinetics do not.
AB  - AIM: The purpose of this study was to identify if sport-specific and
      cardiopulmonary exercise testing differentiated professional from amateur soccer
      players. METHODS: Thirty six men comprising 18 professional (mean+/-s: age 23.2+/
      2.4 years) and 18 amateur (mean+/-SD: age 21.1+/-1.6 years) soccer players
      participated and performed four tests on separate occasions: 1) a graded exercise
      test to determine VO2max; 2) four exercise transients from walking to 80%Delta
      for the determination of VO2 kinetics; 3) the Yo-Yo Intermittent Recovery Test
      level 2 (Yo-Yo IR2) and 4) a repeated sprint test (RST). RESULTS: The players did
      not differ in VO2max (professional 56.5+/-2.9 mL.kg-1.min-1; amateur 55.7+/-3.5
      mL.kg-1.min-1: P=0.484) or VO2 kinetic fundamental measures (tau1 onset,
      professional 24.5+/-3.2 s; amateur 24.0+/-1.8 s: tau1 cessation, professional
      28.7+/-2.8 s; amateur 29.3+/-3.5 s: P=0.923). However, the amateurs were
      outperformed in the Yo-Yo IR2 (Professional 966+/-153 m; Amateur 840+/-156 m)
      (P=0.034) and RST (best time, professional 6.46+/-0.27 s; amateur 6.84+/-0.24 s,
      P=0.012). CONCLUSION: Performance indices derived from field-based sport-specific
      performance tests identified significant differences between professional and
      amateur players (P<0.05). However, neither tests of VO2 kinetics nor VO2max
      differentiated between groups, suggesting laboratory tests of cardiorespiratory
      parameters are probably less consequential to soccer than sport-specific field
      based observations.

PMID- 22648463
TI  - High intensity interval exercise training in overweight young women.
AB  - AIM: The purpose of this study was intended to evaluate the effects of a high
      intensity interval training (HIIT) program on the body composition, cardiac
      function and aerobic capacity in overweight young women. METHODS: Sixty female
      university students (aged 19-20, BMI>=25kg/m2 and percentage body fat >= 30%)
      were chosen and then randomly assigned to each of the HIIT group, the moderate
      intensity continuous training (MICT) group and the non-training control group.
      The subjects in both the HIIT and MICT groups underwent exercise training five
      times per week for 12 weeks. In each of the training sessions, the HIIT group
      performed interval exercises at the individualized heart rate (HR) of 85% of
      VO2max and separated by brief periods of low intensity activity (HR at 50% of
      VO2max), while the MICT group did continuous walking and/or jogging at the
      individualized HR of 50% of VO2max. RESULTS: Both of these exercise training
      programs produced significant improvements in the subjects' body composition,
      left ventricular ejection fraction, heart rate at rest, maximal oxygen uptake and
      ventilatory threshold. However, the HIIT group achieved better results than those
      in the MICT group, as it was evaluated by the amount of the effect size. The
      control group did not achieve any change in all of the measured variables.
      CONCLUSION: The tangible results achieved by our relatively large groups of
      homogeneous subjects have demonstrated that the HIIT program is an effective
      measure for the treatment of young women who are overweight.

PMID- 22648464
TI  - Criterion-related validity of field-based muscular fitness tests in youth.
AB  - AIM: The purpose of the present study was to analyze the association between
      isokinetic strength and field-based muscular fitness tests in youth. METHODS: One
      hundred twenty-six adolescents (14.4+/-1.7 y) participated in the study. Upper
      and lower body isokinetic strength were measured at preset angular velocities of
      90 o/s and 60 o/s, respectively. Muscular fitness was also assessed by means of
      field-based tests: handgrip strength, bent and extended arm hang tests, standing
      long jump, squat jump, countermovement jump and Abalakov jump. Height, weight and
      skinfold thickness were used to estimate body composition. RESULTS: All field
      based tests were significantly associated with isokinetic peak torque and power
      (P<0.001 in all cases). Handgrip strength and standing long jump showed the
      highest associations with the isokinetic parameters (0.61<=r<=0.87;
      0.39<=R2<=0.76). Weight-bearing field tests increased on average 20 % their
      association (R2) with isokinetic parameters when standardized by individual's
      body weight (test score * weight), while the average increase was 16 % when
      standardized by fat-free mass (test score * fat-free mass). CONCLUSION: Handgrip
      strength and standing long jump tests seem to be the most valid field-based
      muscular fitness tests when compared to isokinetic strength. These tests can be
      useful to assess muscular fitness in young people when laboratory methods are not
      feasible.

PMID- 22648465
TI  - One set resistance training: effect on body composition in overweight young
      adults.
AB  - AIM: This study evaluate the impact of a 6-month, 1-set RT protocol on changes in
      weight and body composition in overweight young adults. METHODS: Sixty-three
      overweight young adults were randomized to RT or control; 55 participants (RT:
      N.=32; C: N.=23; BMI=27.3+2.9; age=20.7+2.7 yrs) competed the 6 month training
      protocol and all assessments. RT consisted of 1-set, 9 exercises, 3 times/wk.,
      with a resistance of 3-6 repetition maximum (RM). Body composition was assessed
      using dual energy X-ray absorptiometry, and strength using 1RM. Participants were
      instructed to maintain their normal ad libitum diet and normal activities of
      daily living. RESULTS: Body weight and BMI increased significantly (P<0.05) in RT
      and C, however; the between group difference was not significant. RT induced a
      mean increase in fat-free mass of 1.5 kg in both males and females with
      significant between groups differences for change in fat-free mass noted in the
      total sample, and in both males and females. Between group differences for change
      in fat mass were not statistically significant in the total sample, or in either
      gender. Significant between group differences for change in % fat were noted in
      the total sample (RT=-0.3%, C=+5.8%, P<0.05) and in females (RT=-3.7%, C=+3.0%,
      P<0.01), but not in males (RT=3.4%, C=9.8%). Significant between group
      differences (P<0.001) were observed for change in chest (RT=45 %, C=3%) and leg
      press (RT=57 %, C=9%) maximal strength. CONCLUSION: A 6 month, 1-set RT program
      in overweight young adults increased fat-free mass and prevented increases in fat
      mass and % fat.

PMID- 22648466
TI  - Acute caffeine ingestion enhances performance and dampens muscle pain following
      resistance exercise to failure.
AB  - This double-blind, within-subjects experiment examined the effects of acute
      caffeine ingestion on perceptions of muscle pain following a bout of high
      intensity, upper-body resistance exercise to failure. Moderately trained males
      (N.=18) ingested a dose of caffeine (5 mg . kg-1) or placebo in a randomised and
      counterbalanced order and 1 hour later completed bench press exercise to failure
      at an intensity of 60% 1 repetition maximum. Repetitions completed was taken as a
      measure of performance, peak heart rate was determined via heart rate telemetry
      during the exercise bout, rating of perceived exertion (RPE) and upper body
      muscle pain was recorded immediately upon failure of the exercise task and peak
      blood lactate concentration was determined post-exercise. Caffeine resulted in
      improved repetitions to failure (t [17]=3.119, P=0.006), greater peak blood
      lactate (t [17] =5.080, P=0.0001) and lower RPE (t 17=-3.431, P=0.003) compared
      to placebo. Muscle pain perception was also significantly lower in the caffeine
      condition compared to placebo (t [17]=-2.567, P=0.04). These results support
      prior studies using aerobic based exercise modes in suggesting that caffeine
      ingestion can dampen exercise-induced muscle pain. Specifically, caffeine
      ingestion enhances muscular strength performance and reduces upper body muscle
      pain perception immediately following a bout of high-intensity resistance
      exercise to failure.

PMID- 22648468
TI  - Epidemiology of recreational archery injuries: implications for archery ranges
      and injury prevention.
AB  - AIM: The aim of this paper was to assess the incidence of injuries in the general
      population caused by participation in the sport of target archery or bowhunting.
      METHODS: Descriptive analysis of a national probability sample of hospital based
      treatments for archery-related injuries, over a 10-year period. RESULTS: The
      leading injuries were lacerations (62+/-2%), which most often occurred through
      mishandling hunting arrows. Puncture wounds accounted for 8+/-1% and foreign
      bodies 6+/-1%, arising from feathers or vanes embedding in the hand, falling onto
      an arrow, or a rupturing arrow shaft. Contusions and abrasions, often caused by
      the bowstring hitting the arm, accounted for 6+/-1% of injuries. Nearly all (99+/
      0.4%) of cases were treated and released. The overall injury rate is 4.4/10000
      participants age 6 and over. CONCLUSION: Contrary to the prevailing perception
      that archery is inherently dangerous, the evidence shows that recreational
      archery is a very safe sport - safer than popular field sports where people risk
      collisions or falls, such as soccer, basketball or baseball. The injury rate from
      lacerations could be significantly reduced if bow hunter education courses
      emphasized safe handling of broadhead arrows. The data suggest that nearly all
      acute injuries in target archery can be prevented through participation in an
      accredited training program and the use of basic protective gear (arm guards and
      shooting gloves). All archery education programs should focus on proper archery
      stance and joint strengthening to minimize chronic shoulder and back injuries.

PMID- 22648467
TI  - The periodized resistance training promotes similar changes in lipid profile in
      middle-aged men and women.
AB  - AIM: The aim of the present study was to evaluate the effects of 16 weeks of
      periodized resistance training in lipid profile in sedentary middle-aged men and
      women. METHODS: Healthy subjects (N.=50), middle-aged men and postmenopausal
      women (>12 months amenorrhea), were randomized into resistance training men
      (RTM), resistance training women (RTW), control group men (CGM) and control group
      women (CGW). They performed three weekly sessions for 16 weeks (9 exercises with
      3 x 8-10 RM and with a 60-90 seconds rest period). RESULTS: Trained groups showed
      significant decrease in total cholesterol (TC) (RTM -23.61%; RTW -21.08%;
      P=0.0001) and LDL-C (RTM -35.68%; RTW -38.53%; P=0.0001). No significant changes
      were observed in HDL-C and triglycerides (TG). No significant changes were found
      in plasma levels of LDL-C, HDL-C and TG for control groups, though there were
      significant differences between CGM and CGW for TC. CONCLUSION: The present
      results indicate that 16 weeks of periodized RT contribute to decrease of
      cardiovascular risk factors, such as LDL-C and TC in middle-aged men and women,
      even without changes in body mass and body mass index.

PMID- 22648469
TI  - Change over three years in adolescents' physical activity levels and patterns
      after a physical activity intervention: play study.
AB  - AIM: This study aimed to determine over a three-year period what the PA levels
      and patterns of adolescents will be after participating in a physical activity
      (PA) intervention. METHODS: African adolescents (158 boys, 211 girls, N.=309)
      from a disadvantaged environment in South Africa with a mean age of 14.9+/-1.4,
      boys and 14.3+/-1.4 girls) participated in the study as a PA intervention group
      (N.=282) and a control group (N.=87). Multi-level modelling (repeated measures
      analysis of covariance (ANCOVA) adjusted for attendance percentage and gender to
      compare the intervention and control groups and repeated measures analysis of
      variance (ANOVA) over time, with a Bonferroni post hoc test were used to
      determine how the variables differ across the various testing opportunities. Week
      and weekend PA levels and patterns were analysed separately. RESULTS: Similar
      mean PA levels were found among the boys during week and weekend baseline
      measurements, with a significantly higher mean PA-level after three years in the
      intervention group. Baseline measurements for girls indicated statistically
      significant mean differences during the week and the weekend, although these mean
      differences were not significant during the end measurements. Boys and girls
      (excluding the intervention group of boys), showed a tendency of declining mean
      PA over the three years. The PA intervention showed a stabilising effect on PA
      levels and contributed to more active choices among the intervention group of
      boys, especially during weekends. CONCLUSION: Participation in similar PA
      interventions is recommended for adolescent boys, with adaptation to the content
      for girls.

PMID- 22648470
TI  - Role of cardiorespiratory fitness and obesity on hemodynamic responses in
      children.
AB  - AIM: The purpose of this study was to examine the effects of cardiorespiratory
      fitness (CRF) and obesity on arterial blood pressure and its determinants at rest
      and during isometric handgrip exercise (IHG) in children. METHODS: Fourty-eight
      healthy children aged 11.6+/-0.3 (mean +/-SE) years, (24 obese or overweight
      [OB/OV]; 24 normal weight [NO]) participated in the study. Both groups were
      divided into fit or unfit subgroups according to children's performance of an
      exercise test (PWC170). Arterial pressure and its determinants were recorded with
      the use of a photoplethysmographic device (FINOMETER) during 5 minutes of rest
      and 3 minutes of IHG at 30% of maximum voluntary contraction. RESULTS: At rest
      and during IHG, unfit OB/OV children had higher systolic, mean arterial pressure,
      and rate pressure product (P<=0.05) than fit OB/OV children whose responses were
      similar to NO children, fit or unfit. Changes from rest, in cardiac output,
      cardiac index, and stroke volume were higher in unfit than in fit OB/OV children
      (P<=0.05). Unfit OB/OV children exceeded their fit counterparts in several
      anthropometric measures. However, CRF was found to have a main effect on systolic
      blood pressure (P=0.05). CONCLUSION: Unfit versus fit OB/OV children had an
      exaggerated systolic blood pressure response at rest and during sympathetic
      activation, presumably coupled with higher cardiac output and cardiac oxygen
      demand. These results highlight the importance of fitness for health maintenance
      in obese and overweight children.

PMID- 22648471
TI  - The role of attentional focus in plyometric training.
AB  - AIM: The purpose of this study was to examine how focusing attention during nine
      weeks of plyometric training influence jumping performance. It was hypothesized
      that participants utilizing an external focus of attention during practice would
      produce greater improvements in jumping behavior compared to participants
      practicing in the internal and control conditions. METHODS: Thirty-six untrained
      but physically active male college students were randomly assigned to 1 of 3
      plyometric groups with a different focus of attention: external (EXF; N.=12),
      internal (INF; N.=12), and control (CON; N.=12). All participants subsequently
      participated in the same an 9-week periodized training program. Standing long
      jump (SLJ), countermovement jump (CMJ) and drop jump (DJ) were tested pre- and
      posttraining intervention. RESULTS: The EXF group exhibited greater improvement
      (P<0.05) in jumping distance for SLJ and height for CMJ than both the INF and CON
      groups, while the enhancement in jumping height for DJ was not superior (P<0.05)
      in the EXF group in comparison with the INF and CON groups. However, the CON
      group showed a greater increase (P<0.05) in jumping height for DJ than the INF
      group. The EXF group increased the range of knee flexion (KF), whereas both the
      INF and CON groups decreased the KF during the CMJ. Additionally, only the CON
      group reduced KF during the execution of the DJ. The EXF group (P<0.05) increased
      contact time, whereas both the INF and CON groups decreased (P<0.05) contact time
      in DJ. The EXF group had significantly (P<0.05) greater vertical ground reaction
      force in CMJ and DJ when compared with the INF and CON groups. CONCLUSION: These
      results suggest that the external focus of attention during plyometric training
      may provide a greater stimulus to jump performance in slow stretch shortening
      cycle (SSC) tasks by producing greater force than adopting the internal and no
      specific focus.

PMID- 22648472
TI  - Genetic markers and explosive leg-muscle strength in elite Italian soccer
      players.
AB  - AIM: The aim of the present paper was to investigate the relationships between
      polymorphisms in ACTN3, ACE and BDKRB2 genes, soccer performance, and explosive
      leg-muscle strength in Italian soccer players. METHODS: We examined 42 top-level
      Italian soccer players (S) and 106 sedentary healthy Italians, as a control group
      (C). chi2 test was used to look for the difference in genotype distribution of
      ACTN3, ACE and BDKRB2 between groups. The data were evaluated by forward stepwise
      multiple regression analysis with the Squat Jump (SJ) and Counter Movement Jump
      (CMJ) as dependent variables, as well as competition level (CL), ACTN-3, ACE and
      BDKRB2 genotypes as independent variables. RESULTS: No significant difference was
      found between groups for ACE, ACTN-3 and BDKRB2 genotype distributions. Forward
      stepwise multiple regression analysis suggests a significant relationship between
      a) SJ vs. CL, ACE, and ACTN-3 and b) CMJ vs. CL. For SJ, the multivariate model
      combining genotypic data and competition level significantly predicted explosive
      leg-muscle strength in soccer players and variance explained by the function was
      23.92%. CONCLUSION: An interaction of two polymorphisms (ACE and ACTN-3) might be
      able to discriminate quantitative traits crucial for the elite soccer
      performance, however the contribution of genetic factors to soccer performance is
      not so high.

PMID- 22648473
TI  - A microfluidic-based device for study of transendothelial invasion of tumor
      aggregates in realtime.
AB  - Circulating tumor aggregates exhibit a high metastatic potential and could
      potentially serve as an important target for cancer therapies. In this study, we
      developed a microfluidic model that reconstitutes and is representative of the
      principal components of biological blood vessels, including vessel cavity,
      endothelium, and perivascular matrix containing chemokines. Using this model, the
      transendothelial invasion of tumor aggregates can be observed and recorded in
      realtime. In this study we analyzed the extravasation process of salivary gland
      adenoid cystic carcinoma (ACC) cell aggregates. ACC aggregates transmigrated
      across the endothelium under the stimulation of chemokine CXCL12. The endothelial
      integrity was irreversibly damaged at the site of transendothelial invasion. The
      transendothelial invasion of ACC aggregates was inhibited by AMD3100, but the
      adhesion of ACC aggregates to the endothelium was not affected by the CXCR4
      antagonist. This model allows for detailed study of the attachment and
      transendothelial invasion of tumor aggregates; thus, it would be a useful tool
      for analysis of the underlying mechanisms of metastasis and for testing novel
      anti-metastasis agents.

PMID- 22648474
TI  - Expressed sequence tags in cultivated peanut (Arachis hypogaea): discovery of
      genes in seed development and response to Ralstonia solanacearum challenge.
AB  - Although an important oil crop, peanut has only 162,030 expressed sequence tags
      (ESTs) publicly available, 86,943 of which are from cultivated plants. More ESTs
      from cultivated peanuts are needed for isolation of stress-resistant, tissue
      specific and developmentally important genes. Here, we generated 63,234 ESTs from
      our 5 constructed peanut cDNA libraries of Ralstonia solanacearum challenged
      roots, R. solanacearum challenged leaves, and unchallenged cultured peanut roots,
      leaves and developing seeds. Among these ESTs, there were 14,547 unique sequences
      with 7,961 tentative consensus sequences and 6,586 singletons. Putative functions
      for 47.8 % of the sequences were identified, including transcription factors,
      tissue-specific genes, genes involved in fatty acid biosynthesis and oil
      formation regulation, and resistance gene analogue genes. Additionally,
      differentially expressed genes, including those involved in ethylene and jasmonic
      acid signal transduction pathways, from both peanut leaves and roots, were
      identified in R. solanacearum challenged samples. This large expression dataset
      from different peanut tissues will be a valuable source for marker development
      and gene expression analysis. It will also be helpful for finding candidate genes
      for fatty acid synthesis and oil formation regulation as well as for studying
      mechanisms of interactions between the peanut host and R. solanacearum pathogen.

PMID- 22648475
TI  - Evidence of 2n microspore production in a natural diploid population of Turnera
      sidoides subsp. carnea and its relevance in the evolution of the T. sidoides
      (Turneraceae) autopolyploid complex.
AB  - Turnera sidoides is a complex of distylous perennial rhizomatous herbs that
      includes five subspecies. Since polyploidy has played a prominent role within
      this species (x = 7), ongoing studies in T. sidoides are focused on the
      understanding of the mechanisms involved in the origin and the establishment of
      polyploids. Therefore, aiming to contribute to the understanding of the mode of
      polyploid formation, in this study we investigated the frequency of unreduced
      microspores in a natural diploid population of T. sidoides subsp. carnea by
      analyzing the size range of pollen and the constitution of the sporads. The
      results showed that some of the individuals studied produced 2n and 4n
      microspores, both in short- and long-styled floral morphs. The analysis performed
      documents the production of unreduced microspores in T. sidoides subsp. carnea
      and provides evidence that support the hypothesis of sexual polyploidization as
      one of the most probable mechanisms involved in the origin of polyploids within
      this species complex. The role of unreduced pollen in the establishment and
      persistence of newly formed polyploids in diploid populations of T. sidoides is
      also discussed.

PMID- 22648476
TI  - Stereotypic behaviors in degenerative dementias.
AB  - Stereotypies are simple or complex involuntary/unvoluntary behaviors, common in
      fronto-temporal dementia (FTD), but not studied in other types of degenerative
      dementias. The aim was to investigate stereotypy frequency and type in patients
      with FTD, Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and
      Parkinson's disease with dementia (PDD) in a multicenter observational study; and
      to investigate the relation of stereotypies to cognitive, behavioral and motor
      impairment. One hundred fifty-five consecutive outpatients (45 AD, 40 FTD, 35 PSP
      and 35 PDD) were studied in four hospitals in northern Italy. Stereotypies were
      examined by the five-domain Stereotypy Rating Inventory. Cognition was examined
      by the Mini Mental State and Frontal Assessment Battery, neuropsychiatric
      symptoms by the Neuropsychiatric Inventory, and motor impairment and invalidity
      by the Unified Parkinson's Disease Rating Scale part III, and activities of daily
      living. Stereotypies were present in all groups. FTD and PDD had the greatest
      frequency of one-domain stereotypies; FTD also had the greatest frequency of two
      or-more domain stereotypies; movement stereotypies were the most common
      stereotypies in all groups. AD patients had fewer stereotypies than the other
      groups. Stereotypies are not exclusive to FTD, but are also fairly common in PSP
      and PDD, though less so in AD. Stereotypies may be underpinned by dysfunctional
      striato-frontal circuits, known to be damaged in PSP and PDD, as well as FTD.

PMID- 22648478
TI  - LGI-1-positive limbic encephalitis: a clinicopathological study.

PMID- 22648477
TI  - CCSVI and MS: a statement from the European Society of neurosonology and cerebral
      hemodynamics.
AB  - To systematically review the ultrasonographic criteria proposed for the diagnosis
      of chronic cerebrospinal venous insufficiency (CCSVI). The authors analyzed the
      five ultrasonographic criteria, four extracranial and one intracranial, suggested
      for the diagnosis of CCSVI in multiple sclerosis (MS), together with the
      references from which these criteria were derived and the main studies that
      explored the physiology of cerebrospinal drainage. The proposed CCSVI criteria
      are questionable due to both methodological and technical errors: criteria 1 and
      3 are based on a scientifically incorrect application of data obtained in a
      different setting; criteria 2 and 4 have never been validated before; criterion 2
      is technically incorrect; criteria 3 and 5 are susceptible to so many external
      factors that it is difficult to state whether the data collected are pathological
      or a variation from the normal. It is also unclear how it was decided that two or
      more of these five ultrasound criteria may be used to diagnose CCSVI, since no
      validation of these criteria was performed by different and independent observers
      nor were they blindly compared with a validated gold-standard investigation. The
      European Society of Neurosonology and Cerebral Hemodynamics (ESNCH) has
      considerable concerns regarding the accuracy of the proposed criteria for CCSVI
      in MS. Therefore, any potentially harmful interventional treatment such as
      transluminal angioplasty and/or stenting should be strongly discouraged.

PMID- 22648479
TI  - Increased strain levels and water content in brain tissue after decompressive
      craniotomy.
AB  - BACKGROUND: At present there is a debate on the effectiveness of the
      decompressive craniotomy (DC). Stretching of axons was speculated to contribute
      to the unfavourable outcome for the patients. The quantification of strain level
      could provide more insight into the potential damage to the axons. The aim of the
      present study was to evaluate the strain level and water content (WC) of the
      brain tissue for both the pre- and post-craniotomy period. METHODS: The
      stretching of brain tissue was quantified retrospectively based on the
      computerised tomography (CT) images of six patients before and after DC by a non
      linear image registration method. WC was related to specific gravity (SG), which
      in turn was related to the Hounsfield unit (HU) value in the CT images by a
      photoelectric correction according to the chemical composition of brain tissue.
      RESULTS: For all the six patients, the strain level showed a substantial increase
      in the brain tissue close to the treated side of DC compared with that found at
      the pre-craniotomy period and ranged from 24 to 55 % at the post-craniotomy
      period. Increase of strain level was also observed at the brain tissue opposite
      to the treated side, however, to a much lesser extent. The mean area of
      craniotomy was found to be 91.1 +/- 12.7 cm(2). The brain tissue volume increased
      from 27 to 127 ml, corresponding to 1.65 % and 8.13 % after DC in all six
      patients. Also, the increased volume seemed to correlate with increased strain
      level. Specifically, the overall WC of brain tissue for two patients evaluated
      presented a significant increase after the treatment compared with the condition
      seen before the treatment. Furthermore, the Glasgow Coma Scale (GCS) improved in
      four patients after the craniotomy, while two patients died. The GCS did not seem
      to correlate with the strain level. CONCLUSIONS: We present a new numerical
      method to quantify the stretching or strain level of brain tissue and WC
      following DC. The significant increase in strain level and WC in the post
      craniotomy period may cause electrophysiological changes in the axons, resulting
      in loss of neuronal function. Hence, this new numerical method provides more
      insight of the consequences following DC and may be used to better define the
      most optimal size and area of the craniotomy in reducing the strain level
      development.

PMID- 22648480
TI  - The Department of Health-supported genetic counsellor training post scheme in
      England: a unique initiative?
AB  - Although the professional title 'genetic counsellor' has wide international
      recognition, formal courses or training programmes in genetic counselling exist
      in only a small number of countries. In 2002, voluntary registration of genetic
      counsellors in the UK began under the auspices of the Genetic Counsellor
      Registration Board. Practitioners are eligible for registration after 2 years of
      genetic counselling practice and prior attainment of either a nursing or
      midwifery qualification with relevant Bachelor's degree or a Master's degree in
      genetic counselling. After a government commitment to increase the genetic
      counsellor workforce, the national professional organisation for genetic
      counsellors obtained government funding to expand training capacity for genetic
      counsellors through a training scheme. The Genetic Counsellor Training Post
      Scheme was designed to ensure that both appropriately qualified nurses and
      Master's level genetic counselling graduates were offered the opportunity to
      undertake a 2-year training period prior to registration. The scheme has proved
      highly successful. Of 43 trainees appointed, 42 went on to work as genetic
      counsellors, and 36 have already gained their professional registration. Details
      of this unique scheme including trainee outcomes and experiences are presented.
      This type of scheme may be appropriate for the development of the genetic
      counselling profession in other countries.

PMID- 22648483
TI  - Deep venous thrombosis and pulmonary embolism.

PMID- 22648482
TI  - Retrograde cochlear implantation in postmeningitic basal turn ossification.
AB  - OBJECTIVES/HYPOTHESIS: Postmeningitic basal turn ossification is a challenge for
      successful cochlear implantation despite the availability of sophisticated
      implants and advanced drill-out procedures. A less complex concept consisting of
      a cochleostomy near the apex with retrograde array insertion is evaluated
      clinically and experimentally with emphasis on imaging of intracochlear array
      morphology. STUDY DESIGN: Retrospective case-control study. METHODS: Outcome,
      hearing performance, and radiological findings including three-dimensional (3D)
      reconstructions were assessed in the long term in eight retrograde implanted ears
      of seven postmeningitic deaf patients and compared to an etiology- and device
      matched control group of 17 basal turn implanted ears of 14 patients.
      Experimental insertions into three autopsy-derived human temporal bones were
      evaluated using high-resolution microtomography, 3D reconstruction, and
      histology. RESULTS: No complications occurred. At the long-term follow-up, the
      average monosyllabic word test scores were 41% for the study group and 67% for
      the control group (P = .03). Radiological follow-up revealed insertion sites into
      either the apical or middle turn and frequent intracochlear array direction
      changes (n = 5). Experimental implantations in temporal bones resulted in folding
      free, retrograde, middle turn insertions (n = 3). CONCLUSIONS: The retrograde
      cochlear implantation is a safe and efficient alternative approach in basal turn
      ossification. Despite a high occurrence of intracochlear array direction changes,
      open set speech discrimination was achieved in all patients. Postoperative
      computed tomography is recommended for fitting the speech processor according to
      intracochlear array positions. The experimental insertion in temporal bones
      helped to optimize the approach.

PMID- 22648484
TI  - Inherited and acquired risk factors for venous thromboembolism.
AB  - Venous thrombosis, or venous thromboembolism, comprises deep vein thrombosis with
      or without symptomatic pulmonary embolus. The development of symptomatic venous
      thrombosis is highly dependent on gene-environment interaction. In most instances
      this interaction results in hypercoagulability (the intermediate phenotype)
      sufficient to result in intraluminal clot formation (the disease phenotype). The
      genetic framework underlying venous thrombosis is complex, and there is a large
      material contribution from disease and interaction with environmental factors.
      For example, venous thrombosis is related to recent hospitalization in
      approximately half of all adult cases. After a first episode of venous thrombosis
      patients are 40 times more likely to suffer a further event compared with
      previously unaffected individuals. However, the risk differs between patients.
      Duration of anticoagulation (lifelong or not) should be made with reference to
      whether an episode of thrombosis was provoked and the presence of other risk
      factors. The results of testing for heritable thrombophilia rarely influence
      duration of treatment.

PMID- 22648485
TI  - Imaging tests in the diagnosis of pulmonary embolism.
AB  - Imaging modalities play an essential role in diagnosing pulmonary embolism (PE).
      Clinical outcome studies demonstrated that PE can be safely ruled out in patients
      with unlikely clinical probability in combination with a normal D-dimer test
      result; in all other patients additional imaging is needed. The aim is to
      accurately confirm or rule out the diagnosis of PE, after which, if indicated,
      anticoagulant treatment can be initiated. Various diagnostic tests are available,
      and this article reviews the different imaging techniques in patients with
      suspected PE. Computed tomographic pulmonary angiography (CTPA) is the imaging
      test of choice because of its high sensitivity and specificity. Compression
      ultrasonography and ventilation perfusion scintigraphy are reserved for patients
      with concomitant suspicion of deep vein thrombosis or contraindication for CTPA.
      Furthermore the diagnostic process in patients with clinically suspected
      recurrent PE, PE during pregnancy, and PE in the elderly and in patients with
      malignancy are discussed.

PMID- 22648486
TI  - Serial limited versus single complete compression ultrasonography for the
      diagnosis of lower extremity deep vein thrombosis.
AB  - The diagnostic approach to deep vein thrombosis (DVT) has evolved during the last
      3 decades. Contrast venography has been replaced by noninvasive tests.
      Compression ultrasonography (CUS) is currently the most widely used diagnostic
      test. Whereas CUS has a high accuracy for proximal DVT (thrombosis of the
      popliteal and more proximal veins), it has been shown to lack sensitivity and
      specificity for distal DVT. Ultrasonography can either be limited to the proximal
      veins and repeated within 1 week (serial limited CUS) or extended to both
      proximal and distal veins and performed on one occasion (single complete CUS).
      Both strategies are reliable diagnostic options for the management of patients
      with suspected DVT. The main limitation of proximal CUS is the need to repeat the
      test once in patients with initial negative findings. Conversely, complete CUS
      detects many distal DVTs for which systematic anticoagulation therapy is
      debatable and exposes patients to potentially unnecessary anticoagulation.
      Incorporation of D-dimer testing and clinical pretest probability assessment in
      the diagnostic algorithm is beneficial because it allows excluding DVT without
      the need for diagnostic imaging in about a third of patients.

PMID- 22648487
TI  - The diagnostic management of recurrent deep vein thrombosis and pulmonary
      embolism.
AB  - The diagnostic management of recurrent venous thromboembolism (VTE) is a clinical
      dilemma. Clinical decision rules are well validated in patients with a first
      episode of clinically suspected VTE but are not validated in patients with a
      suspected recurrent event. D-dimer testing could safely exclude a recurrent VTE
      but is subject to several limitations. Imaging could objectively exclude or
      establish the diagnosis of recurrent VTE, but due to persistent residual
      abnormalities after the first or previous event, imaging interpretation can be
      difficult. To limit the presence of uncertain imaging test results, a
      standardized baseline examination after anticoagulation cessation should be
      considered. This review will elaborate on these issues and will discuss the
      recent advancements in this area.

PMID- 22648488
TI  - Triaging in pulmonary embolism.
AB  - Risk stratification of patients with pulmonary embolism represents an important
      step and may help to guide initial therapeutic management. Pulmonary embolism can
      be stratified into several groups, with different risk of early death or
      complications based on the presence of several risk factors. High-risk pulmonary
      embolism is defined by shock or peripheral signs of hypoperfusion. It is a life
      threatening emergency with high short-term mortality (>25%) requiring specific
      therapeutic strategy with inotropic agents and fibrinolysis. In normotensive
      patients with pulmonary embolism, the presence of right ventricular dysfunction
      assessed by echocardiography or myocardial injury based on elevated levels of
      biomarkers, is associated with an intermediate risk of early death. These
      patients require close monitoring, and the role of thrombolytic treatment is
      currently assessed in a large trial. Lastly, patients with normotensive pulmonary
      embolism and without right ventricular dysfunction or myocardial injury have a
      low risk of death and complications. These patients may be candidates for home
      treatment. Several scores combining these risk factors have been described.

PMID- 22648489
TI  - Thromboprophylaxis in surgical and medical patients.
AB  - Venous thromboembolism (VTE) remains the most common preventable cause of death
      in hospitalized patients. There is much evidence to show the efficacy of
      prophylactic strategies to prevent VTE in at-risk hospitalized patients. For
      example, pharmacological prophylaxis reduces the risk of pulmonary embolism by
      75% in general surgical patients and by 57% in medical patients. Thus
      international guidelines strongly recommend effective preventive strategies for
      all hospitalized patients defined as moderate to high risk for VTE. Effective
      pharmacological thromboprophylaxis includes low-dose unfractionated heparin
      (UFH), low molecular weight heparin (LMWH), fondaparinux, and warfarin.
      Mechanical prophylaxis with graduated compression stockings and intermittent
      pneumatic compression is also recommended as an alternative or in combination
      with pharmacological prophylaxis. Although the volume of evidence supporting the
      use of thromboprophylaxis is growing, the number of patients receiving adequate
      prophylaxis is not. Several studies have shown that nearly half of the patients
      undergoing major surgery or hospitalized for medical illnesses do not receive
      appropriate antithrombotic prophylaxis. Reducing the discrepancy between evidence
      based recommendations and clinical practice seems to be a cost-effective goal.
      Developing and promoting local protocols and educational activities to encourage
      prophylaxis in daily clinical practice may be effective. New oral anticoagulant
      drugs with potentially favorable pharmacokinetic and pharmacodynamic
      characteristics have been developed. After the positive results of phase 3
      clinical trials, some of these drugs have been approved for clinical use in the
      prevention of VTE in the high-risk setting of major orthopedic surgery. These
      agents include the direct thrombin inhibitor dabigatran etexilate and the direct
      factor Xa inhibitors rivaroxaban and apixaban.

PMID- 22648490
TI  - Interventional approaches in VTE treatment (vena cava filters, catheter-guided
      thrombolysis, thrombosuction).
AB  - Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary
      embolism (PE), is the third most common cardiovascular pathology after coronary
      disease and cerebrovascular diseases and is responsible for significant morbidity
      and mortality in the general population. Full-dose anticoagulation is the
      standard therapy for VTE, both the acute phase and the prolonged treatment. The
      latest guidelines of the American College of Chest Physicians recommend treatment
      with a full-dose of unfractionated heparin (UFH), low-molecular-weight-heparin
      (LMWH), fondaparinux, vitamin K antagonist (VKA), or systemically administered
      thrombolytics for most of the patients with objectively confirmed VTE. Catheter
      guided thrombolysis and thrombosuction are interventional approaches that should
      be used only in selected populations; interruption of the inferior vena cava
      (IVC) with a filter can be performed to prevent life-threatening PE in patients
      with VTE and contraindications to anticoagulant treatment, bleeding complications
      during antithrombotic treatment, or VTE recurrences, despite optimal
      anticoagulation. This review summarizes the currently available literature
      regarding interventional approaches in VTE treatment (vena cava filters, catheter
      guided thrombolysis, thrombosuction), discusses their efficacy and safety, and
      reviews the appropriate indications for their use in daily clinical practice.

PMID- 22648491
TI  - Medical therapy in venous thromboembolism.
AB  - Immediate intense anticoagulation with parenteral anticoagulants (heparin or
      fondaparinux) followed by vitamin K antagonists is the current standard therapy
      for deep vein thrombosis (DVT) or nonmassive pulmonary embolism. In the future,
      new oral anticoagulants may replace not only vitamin K antagonists but also
      initial parenteral anticoagulation. Duration of anticoagulation should be at
      least 3 months because shorter courses double the recurrence rates. More
      prolonged anticoagulation therapy may be warranted in the presence of specific
      clinical risk factors. Global markers of coagulation, particularly D-dimer, may
      discriminate low- and high-risk patients. Models that combine clinical
      characteristics and laboratory markers further improve prediction of the
      recurrence risk in individual patients, but these models await validation before
      they can be applied in routine care.

PMID- 22648492
TI  - New anticoagulants in the treatment of VTE.
AB  - Low molecular weight heparins (LMWHs) and vitamin K antagonists make up the
      cornerstone of therapy for patients with venous thromboembolism (VTE) but have
      drawbacks making their use difficult in daily practice. Current research focuses
      on the development of new anticoagulant drugs that could be administered orally
      at a fixed dose, with fewer food and drug interactions and no need for monitoring
      or dose adjustment. Several new drugs are tested in noninferiority trials, either
      as a single-drug approach treatment (e.g., rivaroxaban or apixaban), or after an
      initial course of LMWH (e.g., dabigatran or edoxaban). Published clinical trials
      demonstrate that rivaroxaban and dabigatran are noninferior to conventional
      treatment in patients with VTE. Several issues remain challenging for physicians,
      such as the lack of antidote and of routinely available monitoring tests. To what
      extent new anticoagulant drugs will change clinical practice is not yet well
      defined. They may facilitate outpatient management of VTE. They might also
      improve the risk-benefit balance of prolonged anticoagulation and therefore
      modify the optimal duration of anticoagulation in VTE patients.

PMID- 22648493
TI  - Chronic pulmonary embolism and pulmonary hypertension.
AB  - Incomplete resolution of acute pulmonary embolism (PE) is frequently observed
      after acute PE and may rarely result in chronic thromboembolic pulmonary
      hypertension (CTEPH). The underlying pathophysiological mechanism is largely
      unknown. Evidence underlines the concept of a dual pulmonary vascular compartment
      model consisting of increased pulmonary vascular resistance by both large vessel
      obstruction and distal small vessel obliteration, the latter initiated by
      pathological vascular remodeling. Up to 40% of patients with established CTEPH
      have no prior history of symptomatic venous thromboembolism. CTEPH is associated
      with a poor prognosis if left untreated. Therefore, the diagnostic approach of
      CTEPH aims at assessing the location and extent of the embolic obstruction,
      establishing the operability and prognosis of the patients and ruling out other
      variations of pulmonary hypertension with distinct indicated treatment. Heart
      catheterization for invasive pressure measurements and pulmonary catheter
      angiography is obligatory for the final diagnosis. Pulmonary
      thromboendarterectomy is the treatment of choice. In certain patients with
      persistent or recurrent pulmonary hypertension after surgery or with inoperable
      disease, pharmacotherapy might be beneficial.

PMID- 22648494
TI  - Venous thromboembolism and arterial complications.
AB  - An increasing body of evidence suggests the likelihood of a link between venous
      and arterial thrombosis. The two vascular complications share several risk
      factors, such as age, obesity, smoking, diabetes mellitus, blood hypertension,
      hypertriglyceridemia, and metabolic syndrome. Moreover, there are many examples
      of conditions accounting for both venous and arterial thrombosis, such as the
      antiphospholipid antibody syndrome, hyperhomocysteinemia, malignancies,
      infections, and the use of hormonal treatment. Finally, several recent studies
      have consistently shown that patients with venous thromboembolism are at a higher
      risk of arterial thrombotic complications than matched control individuals. We,
      therefore, speculate the two vascular complications are simultaneously triggered
      by biological stimuli responsible for activating coagulation and inflammatory
      pathways in both the arterial and the venous system. Future studies are needed to
      clarify the nature of this association, to assess its extent, and to evaluate its
      implications for clinical practice.

PMID- 22648496
TI  - Breast cancer.

PMID- 22648497
TI  - The hard facts.

PMID- 22648498
TI  - Molecular oncology: The positive in the negative.

PMID- 22648499
TI  - Pregnancy: Delivery from breast cancer.

PMID- 22648500
TI  - Metastasis: The rude awakening.

PMID- 22648501
TI  - Perspective: The right trials.

PMID- 22648502
TI  - Risk analysis: A dense issue.

PMID- 22648503
TI  - Exercise: Powering up.

PMID- 22648504
TI  - Environment and genetics: Making sense of the noise.

PMID- 22648505
TI  - Perspective: Not just for women.

PMID- 22648506
TI  - Influence of diet on fecundity, immune defense and content of 2-isopropyl-3
      methoxypyrazine in Harmonia axyridis Pallas.
AB  - Food type can affect all functional aspects of an insect's life. We investigated
      the effects of different diet regimes on life history parameters of the ladybird
      beetle Harmonia axyridis. Furthermore, we tested the importance of elytral color,
      sex, and diet on chemical and immune defense in this species. We also compared
      hemolymph from cohorts of H. axyridis and Coccinella septempunctata (Coleoptera:
      Coccinellidae) fed different diets to examine effects on the 2-isopropyl-3
      methoxypyrazine (IPMP) content in these beetles. No effects of diet on the
      duration of larval development and on adult weight were found. We detected,
      however, significantly higher fecundity and oviposition rates when female H.
      axyridis were reared on pea aphids than when reared on eggs of Ephestia
      kuehniella. Males and females did not differ in their immune response. Elytral
      color affected both immune defense and chemical defense. The antimicrobial
      activity of the hemolymph differed only when morphotypes were tested against E.
      coli. Moreover, we observed an effect of elytral pigmentation on IPMP content.
      The succinea 2 type (orange without dots) had the lowest IPMP content in two out
      of three feeding regimes compared to the succinea 1 (orange with dots) type.
      Depending on diet, IPMP contents differed in both species leading to higher
      contents either in H. axyridis or C. septempunctata. Furthermore, aphid species
      ingested during larval development significantly affected IPMP content in adult
      beetles. These results implicate new aspects for risk assessment of H. axyridis
      in viticulture.

PMID- 22648507
TI  - Quorum sensing of bacteria and trans-kingdom interactions of N-acyl homoserine
      lactones with eukaryotes.
AB  - Many environmental and interactive important traits of bacteria, such as
      antibiotic, siderophore or exoenzyme (like cellulose, pectinase) production,
      virulence factors of pathogens, as well as symbiotic interactions, are regulated
      in a population density-dependent manner by using small signaling molecules. This
      phenomenon, called quorum sensing (QS), is widespread among bacteria. Many
      different bacterial species are communicating or "speaking" through diffusible
      small molecules. The production often is sophisticatedly regulated via an
      autoinducing mechanism. A good example is the production of N-acyl homoserine
      lactones (AHL), which occur in many variations of molecular structure in a wide
      variety of Gram-negative bacteria. In Gram-positive bacteria, other compounds,
      such as peptides, regulate cellular activity and behavior by sensing the cell
      density. The degradation of the signaling molecule--called quorum quenching--is
      probably another important integral part in the complex quorum sensing circuit.
      Most interestingly, bacterial quorum sensing molecules also are recognized by
      eukaryotes that are colonized by QS-active bacteria. In this case, the cross
      kingdom interaction can lead to specific adjustment and physiological adaptations
      in the colonized eukaryote. The responses are manifold, such as modifications of
      the defense system, modulation of the immune response, or changes in the hormonal
      status and growth responses. Thus, the interaction with the quorum sensing
      signaling molecules of bacteria can profoundly change the physiology of higher
      organisms too. Higher organisms are obligatorily associated with microbial
      communities, and these truly multi-organismic consortia, which are also called
      holobionts, can actually be steered via multiple interlinked signaling substances
      that originate not only from the host but also from the associated bacteria.

PMID- 22648508
TI  - Short latency activation of cortex during clinically effective subthalamic deep
      brain stimulation for Parkinson's disease.
AB  - Subthalamic deep brain stimulation (DBS) is superior to medical therapy for the
      motor symptoms of advanced Parkinson's disease (PD), and additional evidence
      suggests that it improves refractory symptoms of essential tremor, primary
      generalized dystonia, and obsessive-compulsive disorder. Despite this, its
      therapeutic mechanism is unknown. We hypothesized that subthalamic stimulation
      activates the cerebral cortex at short latencies after stimulus onset during
      clinically effective stimulation for PD. In 5 subjects (six hemispheres), EEG
      measured the response of cortex to subthalamic stimulation across a range of
      stimulation voltages and frequencies. Novel analytical techniques reversed the
      anode and cathode electrode contacts and summed the resulting pair of event
      related potentials to suppress the stimulation artifact. We found that
      subthalamic brain stimulation at 20 Hz activates the somatosensory cortex at
      discrete latencies (mean latencies: 1.0 +/- 0.4, 5.7 +/- 1.1, and 22.2 +/- 1.8
      ms, denoted as R1, R2, and R3, respectively). The amplitude of the short latency
      peak (R1) during clinically effective high-frequency stimulation is nonlinearly
      dependent on stimulation voltage (P < 0.001; repeated-measures analysis of
      variance), and its latency is less variable than that of R3 (1.02 versus 19.46
      ms; P < 0.001, Levene's test). We conclude that clinically effective subthalamic
      brain stimulation in humans with PD activates the cerebral cortex at 1 ms after
      stimulus onset, most likely by antidromic activation. These findings suggest that
      alteration of the precise timing of action potentials in cortical neurons with
      axonal projections to the subthalamic region may be an important component of the
      therapeutic mechanism of subthalamic brain stimulation.

PMID- 22648509
TI  - PKNOX2 is associated with formal thought disorder in schizophrenia: a meta
      analysis of two genome-wide association studies.
AB  - Formal thought disorder (FTD), or disorganized speech, is one of the central
      signs of schizophrenia; however, little is known about the etiology of FTD. To
      identify new genetic loci associated with FTD, we conducted the first genome-wide
      association meta-analysis of two datasets of 835 cases of FTD and 2,694 controls
      with 729,454 single-nucleotide polymorphisms (SNPs). Logistic regression analysis
      of FTD as a binary trait, adjusted for age and sex, was performed using PLINK.
      For meta-analysis of two datasets, the fixed-effect model in PLINK was applied.
      Through meta-analysis we identified 61 SNPs associated with FTD with p < 10(-4).
      The most significant association with FTD was observed with rs1783925 (p = 4.4 *
      10(-7)) within PKNOX2 gene at 11q24.2 while the second interesting locus was
      rs2277644 (p = 1.18 * 10(-5)) within MYH13 at 17p13. Haplotype analyses of PKNOX2
      and MYH13 loci further supported the associations with FTD. The third locus was
      PHF2 at 9q22.31 (the top SNP was rs12238738 with p = 2.08 * 10(-5)) while the
      fourth locus was GPC6 at 13q32 (the top SNP was rs17196161 with p = 3.12 * 10(
      5)). In conclusion, we identified four new loci (PKNOX2, MYH13, PHF2, and GPC6)
      associated with FTD. These findings offer the potential for new insights into the
      pathogenesis of FTD and schizophrenia.

PMID- 22648510
TI  - Baclofen modulates the expression and release of neurotrophins in schwann-like
      adipose stem cells.
AB  - Neurotrophins are a group of polypeptides that specifically influence neuronal
      activity during development and adult life in the central and peripheral nervous
      system (PNS). In particular, Schwann cells (SC) in the PNS exert a neurotrophic
      role following up-regulation of several growth factors, including nerve growth
      factor (NGF) and brain derived neurotrophic factor (BDNF). Also SC-like cells
      derived from adipose tissue (dASC), which have molecular and functional
      properties similar to SC, can produce and secrete NGF and BDNF. Interestingly,
      gamma-aminobutyric acid (GABA) and its receptors have been also suggested as
      modulators of development and myelination in PNS. Therefore, it was interesting
      to investigate whether the stimulation of the GABA-B receptor may regulate the
      expression of neurotrophins in SC and dASC. Our findings demonstrated that the
      specific GABA-B receptors agonist baclofen influences the expression and the
      secretion NGF and BDNF. In particular, 2 and 24 h of baclofen exposure lead to
      increased neurotrophins expression in both SC and dASC, as measured by western
      blot. Moreover, enzyme-linked immunosorbent assay showed that also the levels of
      released neurotrophins were modified after baclofen treatments. The possibility
      to modulate the neurotrophic potential of adult stem cell, acting on functional
      GABAergic receptors, could represent a novel pharmacological approach to improve
      nerve regeneration.

PMID- 22648511
TI  - PACAP immunoreactivity in human malignant tumor samples and cardiac diseases.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic and
      multifunctional neuropeptide having important roles in various physiological
      processes. Recent trends in PACAP research point to the clinical introduction of
      PACAP or its analogs/fragments possibly in the near future. Recently, we have
      shown the presence of PACAP in human plasma, milk, placenta, and follicular fluid
      samples. However, relatively few data are available on PACAP in human tissues
      from patients with different disorders. The aim of the present study was to
      determine, by radioimmunoassay, the tissue level of PACAP38-like immunoreactivity
      (LI) and PACAP27-LI in different primary non-small cell lung cancer, colon tumor
      samples, and in cardiac muscle samples from patients suffering from ischemic
      heart disease and valvular disorders. We also labeled the PAC1 receptors in human
      cardiac cells. All samples showed significantly higher PACAP38-LI compared with
      PACAP27-LI. We found significantly lower levels of PACAP38-LI and PACAP27-LI in
      tumoral and peripheral samples compared with normal healthy tissue in both lung
      and colon cancers. Further investigations are necessary to describe the exact
      function of PACAP in oncogenesis. We showed that PACAP38-LI and PACAP27-LI are
      significantly higher in ischemic heart diseases compared with valvular
      abnormalities, suggesting that PACAP might play a role in ischemic heart
      disorders.

PMID- 22648512
TI  - Antibody-mediated inhibition of integrin alpha5beta1 blocks neurotoxic prion
      peptide PrP106-126-induced activation of BV2 microglia.
AB  - Microglial activation is a characteristic feature of the pathogenesis of prion
      diseases. The identification of cell surface molecules that mediate the prion
      protein (PrP) synthetic peptide interaction with microglia is of great
      significance as it represents potential target molecules to modulate the events
      leading to the pathophysiology of prion diseases. Here, we carried out in vitro
      experiments to investigate the involvement of alpha5beta1 integrin in neurotoxic
      prion peptide PrP(106-126)-induced activation of BV2 microglia. The results
      showed that the exposure to PrP(106-126) upregulated the mRNA expression of
      proinflammatory factors (IL-1 beta, IL-6, and iNOS) and NALP3 inflammasome
      components (NALP3 and ASC), increased the release of iNOS and its product nitric
      oxide, and stimulated NF-kappaB activation. Blockade of alpha5beta1 integrin with
      monoclonal antibody BMC5 prior to PrP(106-126) treatment abrogated the
      upregulation of the mRNA expression of IL-1 beta, IL-6, iNOS, and ASC, but had no
      effect on the mRNA expression of NALP3, blocked the release of iNOS and nitric
      oxide, and inhibited NF-kappaB activation. These results suggest that alpha5beta1
      integrin is involved in the PrP(106-126)-induced microglial activation through
      the participation in the activation of NF-kappaB and NALP3/ASC inflammasome. Our
      study unveils a previously unidentified role of alpha5beta1 integrin as an
      intermediate signaling molecule in neurotoxic prion peptides-microglia
      interactions and identifies a potential molecular target for the modulation of
      prion-induced microglial activation.

PMID- 22648513
TI  - Prothrombin complex concentrates in emergency bleeding disorders.
AB  - The use of prothrombin complex concentrates (PCCs), a heterogeneous combination
      of coagulation factors and counterbalancing inhibitor components, has broadened
      in recent years beyond single-factor replacement in conditions such as hemophilia
      B, to encompass emergency reversal of anticoagulation secondary to oral vitamin K
      antagonists, ie, warfarin therapy. PCCs also have been studied in other bleeding
      disorders, such as surgery-related and trauma-related bleeding. This review
      provides an updated examination of the differences among PCC formulations, their
      potential role in the management of bleeding disorders, and the primary safety
      issues affecting their use. Am. J. Hematol. 2012. (c) 2012 Wiley Periodicals,
      Inc.

PMID- 22648514
TI  - 82Rb PET myocardial perfusion imaging is superior to 99mTc-labelled agent SPECT
      in patients with known or suspected coronary artery disease.
AB  - PURPOSE: We compared the quality, interpretive confidence and interreader
      agreement between SPECT and PET myocardial perfusion imaging (MPI) in the same
      group of patients. METHODS: The study group comprised 27 patients (age 55 +/- 8.5
      years, 12 men) with known or suspected coronary artery disease (CAD) who had
      undergone gated rest/stress MPI with (99m)Tc-labelled agent SPECT (with and
      without attenuation correction, AC), and subsequent clinical confirmation with
      (82)Rb PET. Three experienced readers blinded to the clinical information
      interpreted all MPI studies. RESULTS: Interreader agreement was significantly
      superior for PET studies than for SPECT studies. Following consensus
      interpretation, the quality of 22 % of the non-AC SPECT studies, 33 % of the AC
      SPECT studies and 63 % of the PET studies was assessed as excellent or good (p =
      0.016). Interpretations were definitely normal or abnormal in 7 % of non-AC SPECT
      studies, 30 % of AC SPECT studies and 85 % of PET studies (p = 0.046). In 13
      patients who had received either invasive coronary angiography or CT angiography
      with no significant CAD, the true-positive rate for significant CAD was higher
      for PET, and the true-negative rate was equal for PET and AC SPECT, and lower for
      non-AC SPECT. CONCLUSION: (82)Rb PET MPI, used as a confirmatory test after
      SPECT, offers improved image quality, interpretive confidence and interreader
      agreement.

PMID- 22648518
TI  - Local recurrence of localized soft tissue sarcoma: a new look at old predictors.
AB  - BACKGROUND: The objective of this study was to examine the effect of known
      predictors of local recurrence of soft tissue sarcoma in a competing risk
      setting. METHODS: The outcome of interest was the cumulative probability of local
      recurrence per category of relevant predictors, with death as a competing event.
      In total, 1668 patients with a localized soft tissue sarcoma of the extremity or
      trunk were included. RESULTS: Tumor size (hazard ratio, 3.3), depth (hazard
      ratio, 3.2), and histologic grade (hazard ratio, 4.5) were the variables that had
      the most effect on the risk of metastasis and, accordingly, were the most likely
      to induce competition. Surgical margins (hazard ratio, 3.3), histologic grade
      (hazard ratio, 2.1), presentation status (hazard ratio, 2.4), and tumor depth
      (hazard ratio, 1.5) were the variables that had the most effect on the risk of
      local recurrence. The 10-year cumulative probabilities of local recurrence were
      markedly different within categories for presentation status (P < .001) and
      surgical margin status (P < .001). However, because of the competing effect of
      death, there was little difference in the 10-year cumulative probabilities of
      local recurrence with regard to tumor depth (12% and 11.4% for deep and
      superficial tumors, respectively; P = .2), tumor size (10.6% and 13.3% for large
      and small tumors, respectively; P = .99), or histologic tumor grade (12.6%,
      10.7%, and 11.1% for high, intermediate, and low-grade tumors, respectively; P =
      .17). CONCLUSIONS: Because of the competition between local recurrence and death,
      histologic tumor grade, tumor size, and tumor depth had little influence on the
      cumulative probability of local recurrence. The authors concluded that local
      management should be based on presentation status and surgical margins rather
      than other, previously acknowledged factors.

PMID- 22648519
TI  - Isoliquiritigenin inhibits the growth of multiple myeloma via blocking IL-6
      signaling.
AB  - Previous studies have suggested that isoliquiritigenin (ISL) has anti
      carcinogenic activity in several kinds of solid tumors, however, little is known
      about the effects of ISL on hematologic malignancies. In this study, we
      investigated the effects of ISL on multiple myeloma (MM) cells both in vitro and
      in vivo. The results showed that ISL could inhibit the growth of MM cells and
      induce their apoptosis in time- and dose-dependent manners. ISL exhibited
      significant anti-tumor activity in MM xenograft models and synergistically
      enhanced the anti-myeloma activity of adriamycin. Further analysis demonstrated
      that ISL not only downregulated IL-6 expression but also significantly decreased
      levels of phosphorylated ERK and STAT3 and could inhibit phosphorylation levels
      of ERK and STAT3 induced by recombinant human IL-6, which are critical signaling
      proteins in IL-6 signaling regulation networks. Taken together, our findings
      suggested that ISL could inhibit the growth of MM via blocking IL-6 signaling and
      might serve as a promising therapeutic agent for treatment of MM.

PMID- 22648520
TI  - Genetic variation in the Nrf2 promoter associates with defective spermatogenesis
      in humans.
AB  - Defective spermatogenesis, which severely impairs male fertility, can be caused
      by excessive reactive oxygen species (ROS). Nuclear factor erythroid 2-related
      factor 2 (Nrf2) regulates transcription of genes encoding enzymes important for
      protection against ROS. In human seminal plasma and spermatozoa, superoxide
      dismutase isoenzymes (SOD) and glutathione S-transferases (GST) are key
      antioxidant enzymes. We hypothesized that decreased function of the Nrf2
      antioxidant response element (ARE) pathway might predispose individuals to male
      infertility. In this study, we identified three functional single nucleotide
      polymorphisms (SNPs) in the Nrf2 promoter regions of 196 idiopathic
      asthenozoospermic patients, 140 idiopathic oligoasthenozoospermic patients, and
      295 controls. We found that two of the Nrf2 SNPs (-617 G > T and -653 T > C) were
      associated with oligoasthenozoospermia (p = 0.001) and individuals with 617 TT
      and 653 TT genotypes had higher risk of oligoasthenozoospermia (p = 0.006 and p =
      0.002). Four haplotypes of Nrf2 promoters were identified, and two of them (GCC
      and TCT) had different frequencies in oligoasthenozoospermic patients than in
      controls (p = 0.019 and p = 0.011). In vitro reporter assay indicated that
      oligoasthenozoospermia associated genotypes of Nrf2 had significantly decreased
      transcriptional capabilities. The GCC and TCT haplotypes both showed lower Nrf2
      mRNA expression in spermatozoa than GCT. TCT also showed decreased levels of
      antioxidant gene GSTM1 and SOD2 mRNA. Analysis of total seminal SOD activity
      elucidated that oligoasthenozoospermic patients had less SOD activity than
      controls. This study is the first to demonstrate a strong association between
      functional polymorphisms in Nrf2 promoters with defective spermatogenesis in
      humans.

PMID- 22648521
TI  - Mesenchymal stromal cells (MSCs): science and f(r)iction.
AB  - Due to their multi-lineage differentiation capacity, support of haematopoiesis,
      immunomodulation and secretion of proregenerative factors, mesenchymal
      stem/stromal cells (MSCs) are in the focus of intense research since decades. The
      literature is replete with reports on their potential in preclinical model
      systems. However, the heterogeneity of the primary cell population as starting
      material and the diverse protocols for isolation and cultivation are hampering
      progress in their clinical application. Consensus on common standards and
      harmonised isolation and characterisation protocols are important to ensure
      safety and efficacy. This review focuses on the recent scientific evidence of
      clinically relevant properties and on the speculative cardiomyogenic and hepatic
      differentiation potential of MSCs. Special emphasis is put on the importance of
      standardisation and harmonisation in clinical-scale manufacturing.

PMID- 22648524
TI  - Branched and linear poly(ethylene imine)-based conjugates: synthetic
      modification, characterization, and application.
AB  - Poly(ethylene imine)s (PEIs) are widely used in different applications, but most
      extensively investigated as non-viral vector systems. The high ability of
      cationic PEIs to complex and condense negatively charged DNA and RNA combined
      with their inherent proton sponge behavior accounts for the excellent efficiency
      in gene delivery. Further chemical modifications of the polymer expand the
      application potential, primarily aiming at increased transfection efficiency,
      cell selectivity and reduced cytotoxicity. Improvements in the synthesis of
      tailor-made PEIs in combination with new in-depth analytical techniques offer the
      possibility to produce highly purified polymers with defined structures. The
      contemporary strategies towards linear and branched poly(ethylene imine)s with
      modified surface characteristics, PEI-based copolymers as well as conjugates with
      bioactive molecules will be discussed. In this regard, the versatile branched
      PEIs have been successfully modified in a statistical manner, whereas the linear
      counterparts open avenues to design and synthesize well-defined architectures, in
      order to exploit their high potential in gene delivery.

PMID- 22648522
TI  - Stem cell-based delivery of Hypoxamir-210 to the infarcted heart: implications on
      stem cell survival and preservation of infarcted heart function.
AB  - This study seeks to test our hypothesis that transgenic induction of miR-210 in
      mesenchymal stem cells (MSC) simulates the pro-survival effects of ischemic
      preconditioning (IPC) and that engraftment of (PC)MSC helps in the functional
      recovery of ischemic heart by miR-210 transfer to host cardiomyocytes through gap
      junctions. miR-210 expression in MSC was achieved by IPC or nanoparticle-based
      transfection of miR-210 plasmid ((miR)MSC) and functional recovery of the
      infarcted heart of rat transplanted with (PC)MSC or (miR)MSC was evaluated. Both
      (PC)MSC and (miR)MSC showed higher survival under lethal anoxia as compared to
      (non-PC)MSC and scramble-transfected MSC ((Sc)MSC) controls with concomitantly
      lower CASP8AP2 expression. Similarly, both (PC)MSC and (miR)MSC survived better
      and accelerated functional recovery of ischemic heart post-transplantation. To
      validate our hypothesis that MSC deliver miR-210 to host cardiomyocytes, in vitro
      co-culture between cardiomyocytes and (PC)MSC or (miR)MSC (using (non-PC)MSC or
      (Sc)MSC as controls) showed co-localization of miR-210 with gap-junctional
      connexin-43. miR-210 transfer to cardiomyocytes was blocked by heptanol
      pretreatment. Moreover, higher survival of cardiomyocytes co-cultured with
      (PC)MSC was observed with concomitant expression of CASP8AP2 as compared to
      cardiomyocytes co-cultured with (non-PC)MSC thus suggesting that miR-210 was
      translocated from MSC to protect host cardiomyocytes. Induction of miR-210 in MSC
      promoted their survival post-engraftment in the infarcted heart. Moreover, direct
      transfer of pro-survival miR-210 from (miR)MSC to host cardiomyocytes led to
      functional recovery of the ischemic heart.

PMID- 22648525
TI  - Production of erythritol and mannitol by Yarrowia lipolytica yeast in media
      containing glycerol.
AB  - Glycerol is a by-product generated in large amounts during the production of
      biofuels. This study presents an alternative means of crude glycerol valorization
      through the production of erythritol and mannitol. In a shake-flasks experiment
      in a buffered medium, nine Yarrowia lipolytica strains were examined for polyols
      production. Three strains (A UV'1, A-15 and Wratislavia K1) were selected as
      promising producers of erythritol or/and mannitol and used in bioreactor batch
      cultures and fed-batch mode. Pure and biodiesel-derived crude glycerol media both
      supplemented (to 2.5 and 3.25 %) and not-supplemented with NaCl were applied. The
      best results for erythritol biosynthesis were achieved in medium with crude
      glycerol supplemented with 2.5 % NaCl. Wratislavia K1 strain produced up to 80.0
      g l-1 erythritol with 0.49 g g-1 yield and productivity of 1.0 g l-1 h-1.
      Erythritol biosynthesis by A UV'1 and A-15 strains was accompanied by the
      simultaneous production of mannitol (up to 27.6 g l-1). Extracellular as well as
      intracellular erythritol and mannitol ratios depended on the glycerol used and
      the presence of NaCl in the medium. The results from this study indicate that
      NaCl addition to the medium improves erythritol biosynthesis, and simultaneously
      inhibits mannitol formation.

PMID- 22648526
TI  - Influence of heat stress and exercise intensity on vastus lateralis muscle and
      prefrontal cortex oxygenation.
AB  - This study examined whether a rise in thermal and cardiovascular strain during
      exercise to exhaustion in the heat at different intensities is associated with
      compromised muscle and cerebral oxygenation. Using near-infrared spectroscopy,
      oxygenation changes in the vastus lateralis and prefrontal cortex of ten subjects
      cycling to exhaustion in 40  degrees C conditions at 60 % (H60%) and 75 % (H75%)
      maximal oxygen uptake (VO2(max)) and for 60 min in 18  degrees C conditions at 60
      % VO2(max) (C60%) were examined. Thermoregulatory and cardiovascular responses
      were also monitored. Rectal temperature reached 38.1  degrees C in the C60%
      trial, 39.7  degrees C (~60 min) and 39.0  degrees C (~27 min) in the H60% and
      H75% trials, respectively (P < 0.001). The core-to-skin temperature gradient was
      similarly narrow (~0.9  degrees C) at exhaustion in the heat, occurring >97 % of
      maximum heart rate and accompanied by significant declines in stroke volume,
      cardiac output and mean arterial pressure (P < 0.01). Vastus lateralis oxygen
      saturation (SmO(2)) declined at the onset of exercise in all conditions,
      remaining similarly depressed at exhaustion in the heat. Prefrontal cortex oxygen
      saturation (ScO(2)) was ~10 % lower at exhaustion in the H60% and H75% trials
      compared with C60% (P < 0.01), which remained above baseline from 15 min onward.
      These findings indicate that changes in SmO(2) and ScO(2) are associated with the
      development of thermal and cardiovascular strain during exercise to exhaustion in
      the heat, which is accelerated by exercise intensity. In locomotor muscles, a
      potential reduction in oxygen delivery may develop, whereas in the brain, the
      progressive reduction in ScO(2) may induce mental fatigue.

PMID- 22648527
TI  - The effect of curcumin on oxaliplatin and cisplatin neurotoxicity in rats: some
      behavioral, biochemical, and histopathological studies.
AB  - Cisplatin is commonly used against several solid tumors, and oxaliplatin is an
      effective cytotoxic drug used in colorectal cancer. A major clinical issue
      affecting 10-40 % of patients treated with cisplatin or oxaliplatin is severe
      peripheral neuropathy causing sensory, motor, and autonomic dysfunction, with
      symptoms including cold sensitivity and neuropathic pain. The biochemical basis
      of the neurotoxicity is uncertain, but is associated with oxidative stress.
      Curcumin (a natural phenolic yellow pigment) has strong antioxidant, anticancer,
      and anti-inflammatory actions. Here we report the possible protective effect of
      curcumin on some cisplatin- and oxaliplatin-induced behavioral, biochemical, and
      histopathological alterations in rats. Twenty-four hours after the end of
      treatments some motor and behavioral tests (motor activity, thermal and
      mechanical nociception, and neuromuscular coordination) were conducted, followed
      by measuring plasma neurotensin platinum concentration in the sciatic nerve, and
      studying the histopathology of the sciatic nerve. Oxaliplatin (4 mg/kg) and
      cisplatin (2 mg/kg) [each given twice weekly, in a total of nine intraperitoneal
      injections over 4.5 weeks] significantly increased plasma neurotensin
      concentration, caused specific damage in the histology of the sciatic nerve and
      produced variable effects in the motor and behavioral tests. Oral curcumin (10
      mg/kg, 4 days before the platinum drug, and thereafter, concomitantly with it for
      4.5 weeks) reversed the alterations in the plasma neurotensin and sciatic nerve
      platinum concentrations, and markedly improved sciatic nerve histology in the
      platinum-treated rats. Larger experiments using a wider dose range of
      oxaliplatin, cisplatin, and curcumin are required to fully elucidate the possible
      protective role of curcumin in platinum-induced neurotoxicity.

PMID- 22648529
TI  - An in vitro study on the DNA damaging effects of phytochemicals partially
      isolated from an extract of Glinus lotoides.
AB  - An extract of Glinus lotoides, a medicinal plant used in Africa and Asia for
      various therapeutic purposes, was recently shown to cause DNA damage in vitro. To
      further explore the potential genotoxicity of this plant, fractionation of the
      crude extract was performed using reverse phase solid-phase extraction and a
      stepwise gradient elution of methanol in water. Four fractions were collected and
      subsequently analysed for their DNA damaging effects in mouse lymphoma cells
      using an alkaline version of the comet assay. To identify potential genotoxic and
      non-genotoxic principles, each fraction was then subjected to liquid
      chromatography coupled to mass spectrometry, LC-MS/MS. 1D and 2D nuclear magnetic
      resonance analyses were used to confirm the identity of some saponins. Although
      fractions containing a mixture of flavonoids and oleanane-type saponins or
      oleanane-type saponins alone produced no DNA damage, those containing hopane-type
      saponins exhibited a pronounced DNA damaging effect without affecting the
      viability of the cells. To conclude, even if this study presents evidence that
      hopane-type of saponins are endowed with a DNA damaging ability, further studies
      are needed before individual saponins can be cited as a culprit for the
      previously reported genotoxicity of the crude extract of G. lotoides.

PMID- 22648530
TI  - Rapid protein concentration, efficient fluorescence labeling and purification on
      a micro/nanofluidics chip.
AB  - Fluorescence analysis has proved to be a powerful detection technique for
      achieving single molecule analysis. However, it usually requires the labeling of
      targets with bright fluorescent tags since most chemicals and biomolecules lack
      fluorescence. Conventional fluorescence labeling methods require a considerable
      quantity of biomolecule samples, long reaction times and extensive
      chromatographic purification procedures. Herein, a micro/nanofluidics device
      integrating a nanochannel in a microfluidics chip has been designed and
      fabricated, which achieves rapid protein concentration, fluorescence labeling,
      and efficient purification of product in a miniaturized and continuous manner. As
      a demonstration, labeling of the proteins bovine serum albumin (BSA) and IgG with
      fluorescein isothiocyanate (FITC) is presented. Compared to conventional methods,
      the present micro/nanofluidics device performs about 10(4)-10(6) times faster BSA
      labeling with 1.6 times higher yields due to the efficient nanoconfinement
      effect, improved mass, and heat transfer in the chip device. The results
      demonstrate that the present micro/nanofluidics device promises rapid and facile
      fluorescence labeling of small amount of reagents such as proteins, nucleic acids
      and other biomolecules with high efficiency.

PMID- 22648531
TI  - Relationship between biodegradation and sorption of phthalate esters and their
      metabolites in natural sediments.
AB  - Regulatory evaluations of commercial chemicals in Canada, the United States, the
      European Union, and other countries aim to identify biodegradation rates of
      chemicals in natural soils and sediments. However, commonly used biodegradation
      testing methods are limited in their capacity to determine biodegradation rates
      under natural environmental conditions. As a result, widely varying
      biodegradation rates have been reported for many very hydrophobic substances.
      This variability causes difficulties in regulatory evaluations, potentially
      leading to chemical misclassification. In the present study, the authors
      developed a model of the relationship between biodegradation, sorption, and
      hydrophobicity, and tested the model in experiments that measured the
      biodegradation rates of a range of di-phthalate esters (DPEs) and mono-phthalate
      esters (MPEs) in natural sediments. The results indicate that DPEs and MPEs have
      the inherent capacity to be quickly degraded by microbes in sediments at a common
      rate, but that DPE biodegradation rates in natural sediments decrease with
      increasing phthalate ester sorption to sediments. The results show that
      inherently biodegradable substances that are subject to a high degree of sorption
      can be expected to exhibit long half-lives in natural sediments. The model
      provides a potential methodology for assessing biodegradation rates in natural
      sediments from inherent biodegradation rates measured in screening tests by
      accounting for chemical sorption. The present study indicates that a reduced rate
      of biodegradation is due to a reduced fraction of freely dissolved chemical
      concentration in the interstitial water, and that the environmental significance
      of sorption-reduced biodegradation rates needs to be viewed in the context of
      risk in chemical evaluations.

PMID- 22648532
TI  - Signal polarity restoration in a 3D inversion recovery sequence used with delayed
      gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC).
AB  - PURPOSE: To develop an image reconstruction algorithm that restores the signal
      polarity in a three-dimensional inversion-recovery (3D-IR) sequence used in
      delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). This approach effectively
      doubles the dynamic range of data used for T1 curve fitting. MATERIALS AND
      METHODS: We applied this reconstruction algorithm to a 3D-IR TFE sequence used
      for T1 mapping, validated the technique in a phantom study, and performed T1-map
      calculations in postosteochondral allograft transplant (OAT) patients. In
      addition, we performed a signal simulation study to assess the algorithm's
      capability to reduce the number of inversion times used in the 3D-IR TFE
      sequence. RESULTS: In comparison to a standard T1-mapping algorithm that uses the
      magnitude of the MRI signal, the proposed algorithm improves the reliability of
      T1 relaxation fits to the inversion-recovery three-parameter function. The signal
      simulation study shows that the number of TI inversion times can be reduced to as
      few as four, without compromising the accuracy of T1 calculations. CONCLUSION:
      This algorithm can be applied to any 2D- or 3D-IR acquisition sequence used in
      conjunction with dGEMRIC. Application of the algorithm improves the reliability
      of T1 calculations and allows the number of TIs to be reduced, leading to shorter
      scan times in dGEMRIC.

PMID- 22648534
TI  - A DNA-templated fluorescent silver nanocluster with enhanced stability.
AB  - We report the discovery of a DNA sequence that templates a highly stable
      fluorescent silver nanocluster. In contrast to other DNA templated silver
      nanoclusters that have a relatively short shelf-life, the fluorescent species
      templated in this new DNA sequence retains significant fluorescence for at least
      a year. Moreover, this new silver nanocluster possesses low cellular toxicity and
      enhanced thermal, oxidative, and chemical stability.

PMID- 22648535
TI  - Role of cytosolic calcium-dependent phospholipase A2 in Alzheimer's disease
      pathogenesis.
AB  - Phospholipases (PLA2s) are a superfamily of enzymes characterized by the ability
      to specifically hydrolyze the sn-2 ester bond of phospholipids generating
      arachidonic acid, utilized in inflammatory responses, and lysophospholipids
      involved in the control of cell membrane remodeling and fluidity. PLA2s have been
      so far considered a crucial element in the etiopathogenesis of several
      neurological diseases such as cerebral ischemia, multiple sclerosis, Parkinson's
      disease, and Alzheimer's disease (AD). In AD, the role of beta-amyloid (Abeta)
      fragments is well established although still more elusive are the molecular
      events of the cascade that from the Abeta accumulation leads to neurodegeneration
      with its clinical manifestations. However, it is well known that inflammation and
      alteration of lipid metabolism are common features of AD brains. Findings
      obtained from in vitro studies, animal models, and human brain imaging analysis
      point towards cPLA2 as a key molecule in the onset and maintenance of the
      neurodegenerative mechanism(s) of AD. In this review, we have focused on the
      molecular and biological evidence of the involvement of cPLA2s in the
      pathogenesis of AD. An insight into the molecular mechanism(s) underlying the
      action and the regulation of cPLA2 is of tremendous interest in the
      pharmaceutical and biotechnology industry in developing selective and potent
      inhibitors able to modulate the onset and/or the outcome of AD.

PMID- 22648538
TI  - Role of skeletal muscle in lung development.
AB  - Skeletal (striated) muscle is one of the four basic tissue types, together with
      the epithelium, connective and nervous tissues. Lungs, on the other hand, develop
      from the foregut and among various cell types contain smooth, but not skeletal
      muscle. Therefore, during earlier stages of development, it is unlikely that
      skeletal muscle and lung depend on each other. However, during the later stages
      of development, respiratory muscle, primarily the diaphragm and the intercostal
      muscles, execute so called fetal breathing-like movements (FBMs), that are
      essential for lung growth and cell differentiation. In fact, the absence of FBMs
      results in pulmonary hypoplasia, the most common cause of death in the first week
      of human neonatal life. Most knowledge on this topic arises from in vivo
      experiments on larger animals and from various in vitro experiments. In the
      current era of mouse mutagenesis and functional genomics, it was our goal to
      develop a mouse model for pulmonary hypoplasia. We employed various genetically
      engineered mice lacking different groups of respiratory muscles or lacking all
      the skeletal muscle and established the criteria for pulmonary hypoplasia in
      mice, and therefore established a mouse model for this disease. We followed up
      this discovery with systematic subtractive microarray analysis approach and
      revealed novel functions in lung development and disease for several molecules.
      We believe that our approach combines elements of both in vivo and in vitro
      approaches and allows us to study the function of a series of molecules in the
      context of lung development and disease and, simultaneously, in the context of
      lung's dependence on skeletal muscle-executed FBMs.

PMID- 22648537
TI  - Effects of second language usage on genetic counseling training and supervision.
AB  - We conducted an exploratory study of the experiences of genetic counselors who
      have either trained or supervised in a second language to assess the relevance of
      this issue to genetic counseling training and supervision. Two hundred-thirty
      NSGC members, CAGC members and genetic counseling students completed the online
      questionnaire. Many of the respondents reported that training and supervision
      differed when another language was involved. Supervisors reported difficulty in
      assessing students' counseling skills and discomfort with an incomplete
      understanding of session content. Students described a greater focus on
      vocabulary at the expense of psychosocial dimensions. Despite this, most felt
      that using another language enhanced their training experience. As such, training
      programs might consider increasing support to these learners and supervisors by
      explicitly acknowledging the challenges they face, providing students with
      language tools to aid in their acquisition of basic skills and providing
      supervisors with new methods for assessing student counseling skills when using
      other languages.

PMID- 22648536
TI  - Integration of the circadian and stress systems: influence of neuropeptides and
      implications for alcohol consumption.
AB  - Disruptions in circadian rhythm and stress reactivity are associated with risks
      of developing neuropsychiatric disorders. The circadian system is organised in a
      hierarchical manner, whereby the master clock is located at the suprachiasmatic
      nucleus, a highly conserved brain region that coordinates the oscillations of
      peripheral clocks. Exposure to psychological stress leads to activation of the
      hypothalamic-pituitary-adrenal axis. There is growing evidence supporting the
      interactions between the circadian and stress systems. Anatomically, the
      circadian and stress signals converge at the paraventricular nucleus (PVN) in the
      hypothalamus. Genes that are involved in the operation of the circadian and
      stress systems, including Clock, Period and CRH are expressed in the PVN. In
      addition, several neuropeptides, including arginin-vasopressin, vasoactive
      intestinal polypeptide, pituitary adenylate cyclase-activating polypeptide and
      the neurotransmitter gamma-aminobutyric acid, are present in the PVN. In this
      review, we will discuss the interaction of circadian genes and stress-response
      genes at the molecular, neurotransmission and behavioural levels. We will place
      particular emphasis on the role of neuropeptides in mediating this interaction.

PMID- 22648539
TI  - Identification, characterization and biological significance of very small
      embryonic-like  stem cells (VSELs) in regenerative medicine.
AB  - The progress of stem cell research, along with technological innovation, has
      brought researchers to focus on the potential role of stem cells in regenerative
      medicine. Ethical and technological issues have limited the applications of human
      embryonic stem cells (hESCs) in this field. As a promising candidate, very small
      embryonic-like stem cells (VSELs) express a multitude of pluripotent stem cell
      markers and demonstrate the ability to differentiate into three germ-layer
      lineages in vitro. Optimized methods for isolation and expansion of VSELs have
      aroused the scientific community's interest in use of this kind of cells for
      regenerative purposes. In this review, we will focus on the biological
      characteristics, as well as the potentiality and remaining challenges in clinical
      application of VSELs. Moreover, a comparison among VSELs and the other
      pluripotent stem cells will be illustrated to highlight the unique advantages of
      VSELs.

PMID- 22648540
TI  - Farnesoid X Receptor (FXR) from normal to malignant state.
AB  - The Farnesoid X Receptor (FXR) is a member of the nuclear receptor superfamily of
      ligand-activated transcription factors, which plays crucial role in bile acid,
      cholesterol, lipid and glucose metabolism, as well as in the development of
      atherosclerosis, intestinal bacterial growth and liver regeneration. FXR is also
      involved in the pathogenesis of cholestatic diseases, non-alcoholic fatty liver
      disease and inflammatory bowel disease. Recent evidence further suggests a key
      role for FXR in apoptosis and cancer. Notably, FXR deficiency promoted intestinal
      inflammation and tumorigenesis, suggesting that FXR activation might be a
      promising strategy in the treatment of colon cancer. FXR deficiency in mice led
      to the development of spontaneous hepatocarcinomas, while FXR inhibition might
      represent a novel therapeutic approach in Barett's esophagus. In breast cancer
      cell lines, FXR agonists down-regulated the breast cancer target gene aromatase.
      FXR inhibited Leydig tumor growth and progression, supporting evidence that FXR
      may be an important regulator of androgen homoeostasis. Further studies are
      required in order to establish possible antitumor effects of this nuclear
      receptor. Either reactivating or inhibiting FXR expression may represent
      promising therapeutic strategies in the treatment of certain types of human
      cancer.

PMID- 22648541
TI  - Hormone receptor status, erbB2 expression and cancer stem cell characteristics of
      circulating tumor cells in breast cancer patients.
AB  - The most important predictor for disease-free and overall survival of breast
      cancer patients is the presence of axillary lymph node metastasis. For
      surveillance during recurrence-free follow-up or in metastatic disease no marker
      is available at the moment. Several trials have shown the prognostic relevance of
      circulating tumor cells (CTC) in early and metastatic breast cancers. Indeed,
      only CTC that exhibit specific molecular characteristics including stem cell
      characteristics, could be able to create new metastasis. Hormone therapy or anti
      erbB2 therapies are prescribed according to the hormone (ERalpha/PR expression)
      and erbB2 status of the initial tumor. Nonetheless, it appears that the CTC, and
      consequently the metastatic cells, may have a very different hormone and erbB2
      status. An optimal individualized treatment could then be obtained by
      characterizing ERalpha and erbB2 status in the CTC and comparing it to the
      primary tumor.

PMID- 22648542
TI  - Widespread epithelioid angiosarcoma with ventricular wall involvement in a dog.
AB  - This paper reports on a canine angiosarcoma, presenting as an "undifferentiated
      metastasizing tumor". A 14-year-old female Cocker Spaniel was referred to the
      University of Extremadura Veterinary Clinic for clinical examination after
      suffering rapid deterioration, with chronic cough, anorexia and cachexia. One
      week after clinical examination, the dog died of right congestive heart failure
      and ventricular arrhythmia. Blood counts revealed lymphopenia and platelet
      depletion. The biochemistry profile was within normal limits, except for a drop
      in blood urea nitrogen. Cytological evaluation of liver and spleen biopsies
      revealed clustered anaplastic cells that lacked convincing tissue
      differentiation. Major findings at necropsy were enlarged spleen and multiple,
      beige to dark-red nodules ranging from 0.5 to 3 cm in diameter in the heart,
      lung, liver and spleen. At histological examination, multiple nests of anaplastic
      epithelioid cells were found in sections from all affected organs.
      Immunohistochemistry revealed widespread expression of CD31 and Factor VIII
      related antigen. The neoplastic cells were negative for CD 18. The diagnosis of
      epithelioid angiosarcoma, localized in the myocardium, lung, liver and spleen was
      made. The primary site of the neoplasm could not be determined.

PMID- 22648543
TI  - Immune response to the long-term grafting of cryopreserved small-diameter
      arterial allografts.
AB  - INTRODUCTION: The viability and immunological response induced by cryopreserved
      arterial allografts remain unclear. This study examines the post-graft behaviour
      of this type of vessel substitute. MATERIALS AND METHODS: Both iliac arteries
      were extracted from Lewis rats (donors) and used to establish groups of
      allogeneic fresh (group I) or cryopreserved (group II) grafts in Fisher-344 rats
      (recipients). Cryopreserved segments for grafting were prepared by automated
      controlled freezing at a cooling rate of 1 degrees C/min followed by storage in
      liquid nitrogen vapour at -145 degrees C for 30 days. Before grafting, the
      vessels were slowly thawed. Animals were sacrificed at 14, 30, 90 and 180 days
      post-surgery when graft specimens were obtained for light and electron microscopy
      and immunohistochemical detection of inflammatory cells (CD45, ED1, CD4, CD8).
      RESULTS: After surgery, 85.71% of the grafts in group I and 82.14% in group II
      were patent. Following long-term implant, both the fresh and cryopreserved
      allografts showed complete loss of the muscle compartment of the media.
      Inflammatory or CD45-positive cells (mainly macrophages and CD8 T-lymphocytes)
      were detected at earlier time points in suture zones and adventitia. In the fresh
      allografts, the number of immunolabelled cells steadily increased until they were
      seen to occupy the entire adventitia at 90 days, with high numbers persisting at
      6 months. In the cryopreserved allografts, this adventitial inflammatory
      infiltrate was significantly reduced. CONCLUSIONS: The cryopreservation/slow
      thawing protocol used diminished the immune response induced by fresh arterial
      allografts improving their behaviour after grafting.

PMID- 22648544
TI  - Recovery of the pubic symphysis on primiparous young and multiparous senescent
      mice at postpartum.
AB  - It has been observed that parturition has a significant effect on female skeletal
      architecture and that age alters musculoskeletal tissues and their functions. We
      therefore hypothesized that multiparity affects the recovery of the pubic
      symphysis in senescent mice at postpartum and the morphology of the interpubic
      tissues. The pubic symphysis of primiparous young, virgin senescent (VS) and
      multiparous senescent (MS) Swiss mice was examined by light microscopy,
      transmission electron microscopy, morphometric analysis and immunohistochemistry.
      The mouse pubic symphysis was remodeled during the first pregnancy: the cellular
      phenotype and morphology changed to ensure a structurally safe birth canal,
      followed by recovery of the interpubic articulation after birth. The morphology
      of the pubic symphysis in the VS group was maintained in a state similar to that
      observed in virgin young mice. In contrast, MS mice exhibited an interpubic
      ligament characterized by extended fibrocyte-like cells, an opened interpubic
      articulation gap, compacted and thin collagen fibrils and scarce galectin-3
      positive cells. Thus, we found that the cellular and extracellular
      characteristics of the pubic symphysis were altered by multiparity in senescent
      mice. These particular tissue characteristics of the MS group might be associated
      with an impaired recovery process at postpartum. Thus, a better understanding of
      the alterations that occur in the birth canal, including the pubic symphysis, due
      to multiparity in reproductively aged mice may contribute to our comprehension of
      the biological mechanisms that modify the skeleton and pelvic ligaments and even
      play a role in the murine model of pelvic organ prolapse.

PMID- 22648545
TI  - Arterial carbon dioxide partial pressure influences CYP4A distribution in the rat
      brain.
AB  - PaCO(2) is an important factor in the regulation of cerebral circulation, and it
      is often used to reduce intracranial pressure through hyperventilation during
      neurosurgery. Changes in concentration can cause changes in CBF (cerebral blood
      flow). 20-HETE is a product of CYP4A-mediated AA (arachidonic acid) metabolism
      and is a powerful endogenous vasoconstrictor; however, its effect on cerebral
      vasoconstriction in cats, dogs and rats remains to be confirmed. It is known that
      changes in PaCO(2) can influence the expression of CYP4A in the rat brain,
      demonstrating the important role of 20-HETE in the mechanism of CO(2)-mediated
      cerebrovascular reactivity. Thirty healthy adult male Wistar rats that weighed
      between 200 g and 250 g were randomly divided into three groups (A, B, and C;
      n=10): group A, normocapnia (PaCO(2) was maintained at approximately 40-45 mmHg);
      group B, hypocapnia (PaCO(2) was maintained at approximately 20-25 mmHg); and
      group C, hypercapnia (PaCO(2) was maintained at approximately 60-65 mmHg).
      Physiological parameters, including HR (heart rate), MBP(mean blood pressure), PH
      and PaCO(2) were recorded every 30 min, and there were no significant hemodynamic
      or body temperature differences. The head was removed after 3.5 h to investigate
      brain CYP4A by immunohistochemistry. Relative to group A, group B exhibited the
      following changes: an increased pH, decreased PaCO(2), and increased brain CYP4A
      protein expression (P<0.05). In contrast, group C exhibited decreased PH,
      increased PaCO(2) and decreased CYP4A protein expression (P<0.05). CO(2) can
      decrease the expression of brain CYP4A during hypercapnia and increase its
      expression during hypocapnia.

PMID- 22648546
TI  - Expression of claudin-1 in canine peripheral nerve sheath tumours and
      perivascular wall tumours. Immunohistochemical study.
AB  - AIMS: A peripheral nerve sheath tumour consists of neoplastic Schwann cells or
      perineurial cells, or a mixture of Schwann cells, perineurial cells and
      fibroblasts. The first aim of the present study was to characterise the
      expression of the claudin-1 tight junction protein in canine intact peripheral
      nerves, canine benign peripheral nerve sheath tumours (cBPNSTs), such as
      schwannomas, neurofibromas, perineuriomas and canine malignant peripheral nerve
      sheath tumours (cMPNSTs), and in different other benign and malignant canine
      spindle cell tumours. The second aim of the present study was to examine whether
      claudin-1 can help to distinguish the subgroups of canine perivascular wall
      tumours. METHODS AND RESULTS: The biopsy and necropsy samples (n=203) included 10
      intact peripheral nerves, 20 cBPNSTs (4 schwannomas, 8 neurofibromas, 8
      perineuriomas), 16 cMPNSTs, 6 psammomatous meningiomas, 6 dermatofibromas, 6
      leiomyomas, 6 myxomas, 4 spindle cell hemangiomas, 2 spindle cell lipomas, 6
      fibrohistiocytic nodules, 8 fibrosarcomas, 8 leiomyosarcomas, 6 myxosarcomas, 8
      hemangiosarcomas, 8 anaplastic sarcomas, 8 amelanotic spindle cell melanomas, 8
      histiocytic sarcomas, 8 spindle cell carcinomas, 8 myoepitheliomas, 8 complex
      carcinomas, 5 cardiac rhabdomyosarcomas, 4 synovial sarcomas, 5 osteosarcomas, 4
      chondrosarcomas and 4 liposarcomas; 31 canine perivascular wall tumours: 10
      hemangiopericytomas, 8 myopericytomas, 6 angioleiomyomas, 4 angioleiomyosarcomas,
      3 angiofibromas. The immunohistochemical panel consisted of humanized antibodies:
      anti-claudin-1, anti-neuron specific enolase, anti-S-100 protein, anti-alpha
      smooth muscle actin, anti-vimentin, anti-cytokeratin AE1-AE3, anti-claudin-5,
      anti-Melan-A and anti-heavy caldesmon, anti-calponin and anti-desmin. The intact
      perineurial cells, all perineuriomas, neurofibromas, cMPNSTs, spindle cell
      carcinomas and epithelial components of the complex carcinomas, all
      hemangiopericytomas and myo-pericytomas showed claudin-1 positivity. The
      schwannomas and other spindle shape cell tumours were negative for claudin-1.
      CONCLUSION: Our findings suggest that an antibody against claudin-1, in
      combination with other antibodies, can be used as a novel diagnostic tool to
      differentiate canine peripheral nerve sheath tumours from other fusocellular
      tumours, and anti-claudin-1, together with other antibodies, can also be used to
      subclassify cBPNSTs. Furthermore, analysis of claudin-1 expression can help to
      differentiate between subgroups of canine perivascular wall tumours.

PMID- 22648547
TI  - Angiotensin AT(1) receptor inhibition-induced apoptosis by RhoA GTPase activation
      and pERK1/2 signaling pathways in neonatal obstructive nephropathy.
AB  - Intrarenal renin-Angiotensin system (RAS) activity is increased during early
      development and is further enhanced by unilateral ureteral obstruction (UUO).  
      We studied the involvement of mitogen-activated protein (MAP) kinase members and
      the RhoA GTPase signaling pathways on the regulation of renal cell response after
      AT1 Angiotensin II receptor inhibition in obstruction.   Neonatal rats subjected
      to sham operation or complete UUO within the first 48 hours of life received
      saline vehicle, Losartan (AT1 inhibitor), or PD-123319 (AT2 inhibitor) during the
      first 14 days of life. Cortex tubular epithelial cell apoptotic response was
      shown by TUNEL and confirmed by electron microscopy associated with mitochondrial
      signaling pathway through the increased proapoptotic ratio Bax/BcL-2, and
      consequently increased caspase 3 expression and activity in obstructed kidney
      before and after Type 1 (AT1) receptor blockade. Non injury of contralateral
      kidney was shown.   The convergence of two independent signal pathways, the RhoA
      GTPase and pERK and concurrent inhibition of JNK MAP kinase, were required for
      the apoptotic response in 14 day kidney obstructed tubular cells either with or
      without Losartan treatment. Absence of increased AT2 protein expression after AT1
      receptor inhibition on day 14 of obstruction was shown. Selective AngiotensinAT2
      receptor inhibition with PD-123319 had no protective effect on the renal response
      to complete 14 day UUO.  We suggest a role of both RhoA GTPase activation and the
      opposing actions of the ERK and JNK-MAP kinase signaling pathways as events
      involved in tubular cell apoptosis regulation in neonatal UUO. The selective AT1
      receptor inhibition had no effect on the renal cellular response in the kidney
      subjected to UUO for 14 days.

PMID- 22648548
TI  - Compartment- and malignance-dependent up-regulation of gamma
      glutamyltranspeptidase and dipetidylpeptidase-IV activity in human brain gliomas.
AB  - gamma-Glutamyltranspeptidase (GGT, syn. gamma-Glutamyltransferase) and
      dipeptidylpeptidase-IV (DPP-IV) activity participates in metabolic and growth
      control of normal and tumor cells by processing biologically active peptides.
      Here, we report on up-regulation of these enzymes in human brain gliomas
      determined by catalytic enzyme histochemistry and immunocytochemistry. Higher
      activity of GGT was found in 50%, 68% and 81% of WHO grade II, III and IV tumors,
      respectively. The process started at/near the microvasculature, from where it
      spread to the parenchyma. On average, the enzyme activity in grade II, III and IV
      gliomas exceeded controls 2.0, 3.0 and 3.5-fold, respectively. Up-regulation of
      DPP-IV-like activity also started at the microvasculature, but mainly in
      pericytes and mononuclear-like cells around the vessels and dispersed in the
      parenchyma. Marked elevation of this enzyme activity, comprising also tumor
      parenchyma, occurred only in grade IV glioblastomas (65% patients; 3.6 times
      above controls) which can, therefore, help in their differentiation from grade
      III gliomas. The increase of total DPP-IV-like activity also included its two
      enzymatic homologs, the canonical DPP-IV/CD26 and FAP-1alpha. The increase in GGT
      is supposed to be a tumor grade dependent response of microvasculature and tumor
      astrocytes to stress induced by tissue hypoxia and/or the metabolic aberrancies.
      The increase in DPP-IV-like activity in high-grade tumors can be attributed to
      inflammatory/scavenging processes performed by the mononuclear-like cells and, in
      glioblastomas, also to regressive changes in the structure and function of the
      microvasculature and tumor parenchyma, including astrocyte stress response. The
      inverse relationship between DPP-IV-like activity and Ki67 in most glioblastomas
      and shorter survival time of patients with low activity of this enzyme also
      suggest its anti-oncogenic effects.

PMID- 22648549
TI  - Myeloid sarcoma and adenocarcinoma of the large bowel as collision tumors: a case
      report.
AB  - Myeloid sarcoma is a rare tumor composed of myeloid cells, localized in an
      extramedullary site, which may be associated with a concurrent myeloid neoplasm
      involving the bone marrow, although such an association is not required. Most
      patients present with acute myeloid leukemia and their prognosis is poor. We
      describe the case of a 76-year old woman with an adenocarcinoma of the right
      colon infiltrating the subserosa synchronous with a myeloid sarcoma at the same
      site; one pericolic lymph node was infiltrated by both tumors. The peculiarities
      of this case are the clinical presentation (as an acute abdomen due to subserosa
      infiltration by the myeloid sarcoma), the coexistence of a myeloid sarcoma with
      an adenocarcinoma of the right colon, and the absence of progression to acute
      leukemia. Coexistence of myeloid sarcoma and adenocarcinoma in the colon is
      probably incidental, and so it appears likely that the two different tumours
      arose from different mechanisms. However, a possible common background is
      conceivable. Some authors have found that p53 has a pivotal role in driving the
      maturation of myeloid stem cells and p53 is, also, involved in colon
      carcinogenesis. In our case, it may be hypothesized that synchronous
      heterogeneous mutations occurred in different types of committed cells or in stem
      cells secondary to p53 loss. Since only one case report has evaluated the
      correlation between myeloid sarcoma and adenocarcinoma of the large bowel,
      further immunohistochemical and molecular studies are needed to clarify the
      pathogenetic relationship between them.

PMID- 22648550
TI  - Expression of basal cell keratin 15 and keratin 19 in oral squamous neoplasms
      represents diverse pathophysiologies.
AB  - Human epithelium contains keratin, which is expressed during differentiation.
      Depending on the target cell type, different types of keratin are expressed, and
      their alterations seem to represent changes in cell properties. The basal cells
      of oral epithelium express keratin 5 (K5), K14, K15 and K19, but their
      alterations in tumors are unclear. To address this issue and to seek possible
      diagnostic application, we examined the expression of these keratins in oral
      squamous cell carcinoma (OSCC) and squamous intraepithelial neoplasm (SIN). cDNA
      microarray analysis of 43 OSCC revealed slight upregulation of KRT14,
      downregulation of KRT15 and KRT19, and unaltered KRT5 expression. There were
      great variations in KRT15 and KRT19 expression across each cancer. Well
      differentiated OSCC tended to express more KRT15 and less KRT19 compared to
      moderately- or poorly-differentiated OSCC. KRT15 was positively correlated with
      differentiation-related keratin, KRT13. These observations were further
      investigated by immunohistochemical examination. K5 and K14 were ubiquitously
      expressed in all 50 OSCC and 50 SIN examined. K15 and K19 were generally
      downregulated, but were considerably retained in about half of the cases and
      showed diverse expression patterns. K15-positive cancers tended to show a well
      differentiated phenotype, and K19-positive cancers tended to show more invasive
      tumor fronts. Most K19-positive cancers appeared to develop with little
      associating SIN. K19 was consistently downregulated in SIN, while K15 was
      downregulated mainly in high grade SIN. In summary, K15 and K19, unlike K5 or
      K14, are expressed variably in both SIN and OSCC, which reflects the differences
      in their pathogenesis and biological behaviors, suggesting their prospective
      applications as markers for subclassifying OSCC and SIN.

PMID- 22648551
TI  - Quantitative changes of the capillary bed in aging human skin.
AB  - The present study focuses on the quantitative changes of the capillary bed in
      aging human skin. Forty-five skin samples were excised from the anterior thoracic
      region of cadavers of caucasian origin in the age range 33-82 years. The
      immunohistochemical method with anti-human CD34 was used for the detection of the
      capillary endothelium. Morphometric analysis was done by Vision Assistant
      software. The capillary bed was quantified by two parameters: capillary area (CA)
      and intercapillary distance (ID) in 6 age groups. Results revealed no
      quantitative changes of the capillary bed up to the age of 60 years. In the
      papillary dermis a significant reduction of the capillary area was seen in the
      7th, 8th and 9th decennium. A considerable decrease, by 33%, was determined in
      the 7th decennium. During the 8th and 9th decennium the capillary area was
      reduced by a further 19% and 13%. In total from the 4th till the 9th decennium,
      the capillary bed in the papillary dermis was diminished by 65%. The
      intercapillary distance in the papillary dermis singnificantly increased during
      the 8th decennium. On the basis of the mutual evaluation of both the observed
      parameters, CA and ICD, the authors supposed that the reduction of the capillary
      bed in the papillary dermis during the 7th decennium was probably caused only by
      the shortening of the capillary loops, which copied flattened dermal papillae,
      and during the 8th decennium also by the decreased number of the capillary loops.
      In the reticular dermis the capillary bed remained unchanged.

PMID- 22648552
TI  - Laryngeal cancer: quantitative and qualitative assessment of research output,
      1945-2010.
AB  - OBJECTIVES/HYPOTHESIS: To provide an in-depth evaluation of research yield in
      laryngeal cancer from 1945 to 2010, using large-scale data analysis, employment
      of bibliometric indicators of production and quality, and density equalizing
      mapping. STUDY DESIGN: Bibliometic analysis incorporating the Web of Science
      Database. METHODS: The search strategy employed was as follows; "TS = ((Laryngeal
      Neoplasm$) OR (Larynx Neoplasm$) OR (Larynx Cancer$) OR (Laryngeal Cancer$))."
      Author and journal data and cooperation networks were computed following analysis
      of combinations of countries and institutions that registered cooperation during
      the study period. Mapping was performed as described by Groneberg-Kloft in 2004.
      RESULTS: A total of 8,658 items relating to laryngeal cancer were published over
      the study period, accounting for 139,700 citations. The United States was the
      most prolific country, accounting for 28.83% (n = 2,496) of total output. Other
      prolific nations included Italy (n = 794) and Germany (n = 792). There were 973
      items published as a consequence of international cooperation; this practice
      increased steadily over time and accounted for 15.58% (88 of 565) of output in
      2010. There were 1,073 different journals publishing articles on laryngeal
      cancer, although the top 20 (1.8%) most prolific titles were together responsible
      for more than 43% of the total output; these were led by Laryngoscope (n = 368)
      and Head and Neck, Journal of the Scientific Specialties (n = 364). A total of
      24,682 authors contributed to the literature on laryngeal cancer; the leading
      author by output was Alfio Ferlito (n = 120); Carlo La Vecchia recorded the
      highest h-index (h = 32). CONCLUSIONS: This work represents the first attempt to
      provide quantitative and qualitative analysis of laryngeal cancer research
      output, whilst in tandem identifying the key bibliometric benchmarks to which
      those involved in the production of that output might aspire.

PMID- 22648554
TI  - Metastasectomy for distant metastatic melanoma: analysis of data from the first
      Multicenter Selective Lymphadenectomy Trial (MSLT-I).
AB  - BACKGROUND: For stage IV melanoma, systemic medical therapy (SMT) is used most
      frequently; surgery is considered an adjunct in selected patients. We
      retrospectively compared survival after surgery with or without SMT versus SMT
      alone for melanoma patients developing distant metastases while enrolled in the
      first Multicenter Selective Lymphadenectomy Trial. METHODS: Patients were
      randomized to wide excision and sentinel node biopsy, or wide excision and nodal
      observation. We evaluated recurrence site, therapy (selected by treating
      clinician), and survival after stage IV diagnosis. RESULTS: Of 291 patients with
      complete data for stage IV recurrence, 161 (55 %) underwent surgery with or
      without SMT. Median survival was 15.8 versus 6.9 months, and 4-year survival was
      20.8 versus 7.0 % for patients receiving surgery with or without SMT versus SMT
      alone (p < 0.0001; hazard ratio 0.406). Surgery with or without SMT conferred a
      survival advantage for patients with M1a (median > 60 months vs. 12.4 months; 4
      year survival 69.3 % vs. 0; p = 0.0106), M1b (median 17.9 vs. 9.1 months; 4-year
      survival 24.1 vs. 14.3 %; p = 0.1143), and M1c (median 15.0 vs. 6.3 months; 4
      year survival 10.5 vs. 4.6 %; p = 0.0001) disease. Patients with multiple
      metastases treated surgically had a survival advantage, and number of operations
      did not reduce survival in the 67 patients (42 %) who had multiple surgeries for
      distant melanoma. CONCLUSIONS: Our findings suggest that over half of stage IV
      patients are candidates for resection and exhibit improved survival over patients
      receiving SMT alone, regardless of site and number of metastases. We have begun a
      multicenter randomized phase III trial comparing surgery versus SMT as initial
      treatment for resectable distant melanoma.

PMID- 22648556
TI  - A new method of measuring acetabular cup anteversion on simulated radiographs.
AB  - PURPOSE: Optimal positioning of acetabular components is crucial for maintaining
      stability of THA. Postoperative assessment of acetabular anteversion is a vital
      but difficult task. Various methods have been devised with good results for
      measuring anteversion on plain radiographs but these methods are either too
      complicated or require special objects like scientific calculators, special
      protectors, tables, etc. A new simplified method of measuring anteversion on
      plain radiographs was created based on basic geometry. METHODS: Anteversion of
      acetabular components was estimated on computer generated images of the
      acetabular cup by our method and compared with two previously established methods
      of Liaw and Pradhan. Measurement was done at 400 different positions of
      acetabular cup and compared with actual values. Another analysis was done after
      adding the femoral head to the acetabular component, thus obscuring some of the
      acetabular rim. RESULTS: Mean and standard deviation of error for our method was
      0.77 degrees  +/- 0.75 degrees  as compared to 0.93 degrees  +/- 0.86 degrees 
      and 0.72 degrees  +/- 0.68 degrees  for the methods of Liaw and Pardhan,
      respectively, with no significant differences from actual values. Maximal errors
      for our method, Liaw's and Pradhan's method were 3 degrees , 4 degrees , and 2.91
      degrees , respectively. On analysis, after the adding femoral head, there was a
      significant error of measurement with Liaw's method, while our method as well as
      Pardhan's remained accurate. All methods showed high inter- and intraobserver
      reliability. CONCLUSION: Our new simplified method of measuring acetabular
      anteversion on plain radiographs is acceptable in comparision to other
      established methods and requires only routinely used goniometer and calliper.

PMID- 22648557
TI  - Metaphyseal locking compression plate as an external fixator for the distal
      tibia.
AB  - PURPOSE: Recently we coined the term supercutaneous plating using a locking
      compression plate (LCP) as an external fixator. The use of this technique in peri
      articular areas is facilitated by the development of anatomical plates with
      various screw sizes. The purpose of this report is to describe our results using
      the metaphyseal locking plate (LCP) as an external fixator in the treatment of
      infected post-traumatic problems of the distal tibia. METHODS: Between August
      2008 and January 2012 a total of seven patients underwent external plating
      ("supercutaneous plating") of the distal tibia using a metaphyseal locking plate.
      Average age was 43 years (range 20-79). Six out of seven patients had a
      documented infection at the time of external plate application. All patients in
      this cohort were followed prospectively at regular intervals by the senior author
      (PK). RESULTS: The plate was in situ for an average of 17.5 weeks (range 6-60).
      There were no clinically significant pin site infections. In four patients the
      plate was kept in place until there was complete consolidation. In three patients
      the external plate was exchanged for formal internal fixation once the infection
      had subsided. At the latest follow-up (average 12.8 months, range 4-31), all
      patients were fully weight bearing with a fully healed tibia. All patients were
      infection-free with well-healed wounds. CONCLUSION: Infection of the distal tibia
      after treatment of traumatic and post-traumatic problems is a challenging
      problem. It is common practice that after initial debridement and hardware
      removal, temporary bony stabilisation is provided by external fixation. Most
      external frames for the lower leg are bulky and cumbersome, causing significant
      problems for the patient. To circumvent these issues, we have successfully used
      an anatomically-contoured metaphyseal locking compression plate as external
      fixator in a series of seven patients for acute or post-traumatic problems of the
      tibia.

PMID- 22648558
TI  - Effect of body mass index on the outcome of children with acute myeloid leukemia.
AB  - BACKGROUND: The effect of body mass index (BMI) on the treatment outcomes of
      children with acute myeloid leukemia (AML) is unclear and needs further
      evaluation. METHODS: Children with AML (n = 314) who were enrolled in 4
      consecutive St. Jude protocols were grouped according to BMI (underweight, <5th
      percentile; healthy weight, 5th to 85th percentile; and overweight/obese, >= 85th
      percentile). RESULTS: Twenty-five patients (8%) were underweight, 86 patients
      (27.4%) were overweight/obese, and 203 patients (64.6%) had healthy weight. The 5
      year overall survival rate of overweight/obese patients (46.5% +/- 7.3%) was
      lower than the rate of patients with healthy weight (67.1% +/- 4.3%; P < .001);
      underweight patients also tended to have lower survival rates (50.6% +/- 10.7%; P
      = .18). In a multivariable analysis that was adjusted for age, leukocyte count,
      French-American-British classification, and study protocols, patients with
      healthy weight had the best survival rate among the 3 groups (P = .01). When BMI
      was considered as continuous variable, patients with lower or higher BMI
      percentiles had worse survival (P = .03). There was no difference in the
      occurrence of induction failure or relapse among BMI groups, although underweight
      and overweight/obese patients had a significantly higher cumulative incidence of
      treatment-related mortality, especially because of infection (P = .009).
      CONCLUSIONS: An unhealthy BMI was associated with worse survival and more
      treatment-related mortality in children with AML. Meticulous supportive care with
      nutritional support and education, infection prophylaxis, and detailed laboratory
      and physical examination is required for these patients. These measures, together
      with pharmacokinetics-guided chemotherapy dosing, may improve outcome.

PMID- 22648560
TI  - Evaluation of six proton pump inhibitors as inhibitors of various human
      cytochromes P450: focus on cytochrome P450 2C19.
AB  - Six proton pump inhibitors (PPIs), omeprazole, lansoprazole, esomeprazole,
      dexlansoprazole, pantoprazole, and rabeprazole, were shown to be weak inhibitors
      of cytochromes P450 (CYP3A4, -2B6, -2D6, -2C9, -2C8, and -1A2) in human liver
      microsomes. In most cases, IC50 values were greater than 40 MUM, except for
      dexlansoprazole and lansoprazole with CYP1A2 (IC50 = ~8 MUM) and esomeprazole
      with CYP2C8 (IC50 = 31 MUM). With the exception of CYP2C19 inhibition by
      omeprazole and esomeprazole (IC50 ratio, 2.5 to 5.9), there was no evidence for a
      marked time-dependent shift in IC50 (IC50 ratio, <= 2) after a 30-min
      preincubation with NADPH. In the absence of preincubation, lansoprazole (IC50 =
      0.73 MUM) and esomeprazole (IC50 = 3.7 MUM) were the most potent CYP2C19
      inhibitors, followed by dexlansoprazole and omeprazole (IC50 = ~7.0 MUM).
      Rabeprazole and pantoprazole (IC50 = >= 25 MUM) were the weakest. A similar
      ranking was obtained with recombinant CYP2C19. Despite the IC50 ranking, after
      consideration of plasma levels (static and dynamic), protein binding, and
      metabolism-dependent inhibition, it is concluded that omeprazole and esomeprazole
      are the most potent CYP2C19 inhibitors. This was confirmed after the incubation
      of the individual PPIs with human primary hepatocytes (in the presence of human
      serum) and by monitoring their impact on diazepam N-demethylase activity at a low
      concentration of diazepam (2 MUM). Data described herein are consistent with
      reports that PPIs are mostly weak inhibitors of cytochromes P450 in vivo.
      However, two members of the PPI class (esomeprazole and omeprazole) are more
      likely to serve as clinically relevant inhibitors of CYP2C19.

PMID- 22648559
TI  - [Multiparametric MRI, elastography, contrastenhanced TRUS. Are there indications
      with reliable diagnostic advantages before prostate biopsy?].
AB  - Prostate cancer (PCA) is the most common malignancy in men with an increasing
      incidence and is responsible for about 11,000 deaths per year in Germany.
      Fortunately, the mortality of PCA has decreased in recent years despite the
      rising incidence reflecting improvements in diagnostic methods. Many new
      innovations in imaging techniques for PCA are available and may be helpful in
      early detection of PCA. Contrast-enhanced sonography, computer-assisted
      sonography, elastography and multiparametric magnetic resonance imaging (MRI)
      seem to be the most promising methods to increase the detection rate of PCA
      during diagnostic work-up. The value of these new innovative techniques
      concerning improvement in PCA detection is reviewed.

PMID- 22648561
TI  - Metabolism and pharmacokinetics of indacaterol in humans.
AB  - The metabolism, pharmacokinetics, and excretion of [(14)C]indacaterol were
      investigated in healthy male subjects. Although indacaterol is administered to
      patients via inhalation, the dose in this study was administered orally. This was
      done to avoid the complications and concerns associated with the administration
      of a radiolabeled compound via the inhalation route. The submilligram doses
      administered in this study made metabolite identification and structural
      elucidation by mass spectrometry especially challenging. In serum, the mean
      t(max), C(max), and AUC(0-last) values were 1.75 h, 0.47 ng/ml, and 1.81 ng .
      h/ml for indacaterol and 2.5 h, 1.4 ngEq/ml, and 27.2 ngEq . h/ml for total
      radioactivity. Unmodified indacaterol was the most abundant drug-related compound
      in the serum, contributing 30% to the total radioactivity in the AUC(0-24h)
      pools, whereas monohydroxylated indacaterol (P26.9), the glucuronide conjugate of
      P26.9 (P19), and the 8-O-glucuronide conjugate of indacaterol (P37) were the most
      abundant metabolites, with each contributing 4 to 13%. In addition, the N
      glucuronide (2-amino) conjugate (P37.7) and two metabolites (P38.2 and P39) that
      resulted from the cleavage about the aminoethanol group linking the
      hydroxyquinolinone and diethylindane moieties had a combined contribution of
      12.5%. For all four subjects in the study, >=90% of the radioactivity dose was
      recovered in the excreta (85% in feces and 10% in urine, mean values). In feces,
      unmodified indacaterol and metabolite P26.9 were the most abundant drug-related
      compounds (54 and 17% of the dose, respectively). In urine, unmodified
      indacaterol accounted for ~0.3% of the dose, with no single metabolite accounting
      for >1.3%.

PMID- 22648562
TI  - Calcium-dependent regulation of the motor activity of recombinant full-length
      Physarum myosin.
AB  - We successfully synthesized full-length and the mutant Physarum myosin and heavy
      meromyosin (HMM) constructs associated with Physarum regulatory light chain and
      essential light chain (PhELC) using Physarum myosin heavy chain in Sf-9 cells,
      and examined their Ca(2+)-mediated regulation. Ca(2+) inhibited the motility and
      ATPase activities of Physarum myosin and HMM. The Ca(2+) effect is also
      reversible at the in vitro motility of Physarum myosin. We demonstrated that full
      length myosin increases the Ca(2+) inhibition more effectively than HMM.
      Furthermore, Ca(2+) did not affect the motility and ATPase activities of the
      mutant Physarum myosin with PhELC that lost Ca(2+)-binding ability. Therefore, we
      conclude that PhELC plays a critical role in Ca(2+)-dependent regulation of
      Physarum myosin.

PMID- 22648563
TI  - Effects of site-directed mutagenesis of Asn116 in the beta-hairpin of the N
      terminal domain of thermolysin on its activity and stability.
AB  - In the N-terminal domain of thermolysin, two anti-parallel beta-strands, Asn112
      Ala113-Phe114-Trp115 and Ser118-Gln119-Met120-Val121-Tyr122 are connected by an
      Asn116-Gly117 turn to form a beta-hairpin structure. In this study, we examined
      the role of Asn116 in the activity and stability of thermolysin by site-directed
      mutagenesis. Of the 19 Asn116 variants, four (N116A, N116D, N116T and N116Q) were
      produced in Escherichia coli, by co-expressing the mature and pro domains
      separately, while the other 15 were not. In the hydrolysis of N-[3-(2
      furyl)acryloyl]-glycyl-L-leucine amide (FAGLA) at 25 degrees C, the intrinsic
      k(cat)/K(m) value of N116D was 320% of that of the wild-type thermolysin (WT),
      and in the hydrolysis of N-carbobenzoxy-L-aspartyl-L-phenylalanine methyl ester
      (ZDFM) at pH 7.5 at 25 degrees C, the k(cat)/K(m) value of N116D was 140% of that
      of WT, indicating that N116D exhibited higher activity than WT. N116Q exhibited
      similar activity as WT, and N116A and N116T exhibited reduced activities. The
      first-order rate constants, k(obs), of the thermal inactivation at 80 degrees C
      were in the order N116A, N116D, N116T > N116Q > WT at all CaCl(2) concentrations
      examined (1-100 mM), indicating that all variants exhibited reduced stabilities.
      These results suggest that Asn116 plays an important role in the activity and
      stability of thermolysin presumably by stabilizing this beta-hairpin structure.

PMID- 22648566
TI  - Mechanistic insights on platinum- and palladium-pincer catalyzed coupling and
      cyclopropanation reactions between olefins.
AB  - The mechanism of M(II)-PNP-pincer catalyzed reaction between (i) ethene, (ii)
      trans-butene with 2-methylbut-2-ene, 2,3-dimethylbut-2-ene and tert-butylbutene
      is examined by using density functional theory methods (where M = Pt or Pd). All
      key intermediates and transition states involved in the reaction are precisely
      located on the respective potential energy surfaces using the popular DFT
      functionals such as mPW1K, M06-2X, and B3LYP in conjunction with the 6-31+G**
      basis set. The reaction between these olefins can lead to a linear coupling
      product or a substituted cyclopropane. The energetic comparison between coupling
      as well as cyclopropanation pathways involving four pairs of olefins for both
      platinum (1-4) and palladium (5-8) catalyzed reactions is performed. The key
      events in the lower energy pathway in the mechanistic course involves (i) a C-C
      bond formation between the metal bound olefin (ethene or trans-butene) and a free
      olefin, and (ii) two successive [1,2] hydrogen migrations in the ensuing
      carbocationic intermediates (1c-4c, and 1d-4d), toward the formation of the
      coupling product. The computed barriers for these steps in the reaction of metal
      bound ethene to free tert-butylbutene (or other butenes) are found to be much
      lower than the corresponding steps when trans-butene is bound to the metal
      pincer. The Gibbs free energy differences between the transition states leading
      to the coupling product (TS(d-e)) and that responsible for cyclopropanated
      product (TS(d-g)) are found to be diminishingly closer in the case of the
      platinum pincer as compared to that in the palladium system. The computed
      energetics indicate that the coupled product prefers to remain as a metal olefin
      complex, consistent with the earlier experimental reports.

PMID- 22648564
TI  - Expression of Beclin 1 and LC3 in FIGO stage I-II cervical squamous cell
      carcinoma and relationship to survival.
AB  - The purpose of this study was to investigate the expression of autophagy-related
      proteins Beclin 1 and LC3 in cervical normal epithelial cells and squamous cancer
      cells, and to evaluate the prognostic significance of Beclin 1 and LC3 expression
      in FIGO stage I-II cervical squamous cell carcinoma. The immunohistochemical
      expression of Beclin 1 and LC3 were evaluated in 26 formalin-fixed paraffin
      embedded cervical normal tissue samples and 50 tumor samples of FIGO stage I-II
      cervical squamous cell carcinoma, respectively. Correlations with
      clinicopathologic characteristics were determined by Chi-square test. The
      prognostic impact of Beclin 1 and LC3 expression in regard to overall survival
      was determined by Kaplan-Meier method. Cervical normal squamous epithelial cells
      and cancer cells expressed high Beclin 1 immunoreactivity in 96.2 % (25/26) and
      28.0 % (14/50) of patients (p = 0.000), and expressed high LC3 immunoreactivity
      in 76.9 % (20/26) and 26.0 % (13/50) of patients, respectively (p = 0.000). The
      expression of both Beclin 1 and LC3 were not associated with age, FIGO stage,
      pathologic differentiation, and lymph node metastasis. The 3-year overall
      survival (OS) rates with low and high expressions of Beclin 1 were 72.2 and 100.0
      %, respectively (p = 0.034). The 3-year OS rates with low and high expressions of
      LC3 were 75.7 and 92.3 %, respectively (p = 0.224). These results show that
      expression level of both Beclin-1 and LC3 were significantly lower in cervical
      squamous cancer cells than normal squamous epithelial cells. The expression of
      Beclin 1 and LC3 may have prognostic significance in early stage cervical
      squamous cell carcinoma.

PMID- 22648567
TI  - Modeling inter-human movement coordination: synchronization governs joint task
      dynamics.
AB  - Human interaction partners tend to synchronize their movements during repetitive
      actions such as walking. Research of inter-human coordination in purely rhythmic
      action tasks reveals that the observed patterns of interaction are dominated by
      synchronization effects. Initiated by our finding that human dyads synchronize
      their arm movements even in a goal-directed action task, we present a step-wise
      approach to a model of inter-human movement coordination. In an experiment, the
      hand trajectories of ten human dyads are recorded. Governed by a dynamical
      process of phase synchronization, the participants establish in-phase as well as
      anti-phase relations. The emerging relations are successfully reproduced by the
      attractor dynamics of coupled phase oscillators inspired by the Kuramoto model.
      Three different methods on transforming the motion trajectories into
      instantaneous phases are investigated and their influence on the model fit to the
      experimental data is evaluated. System identification technique allows us to
      estimate the model parameters, which are the coupling strength and the frequency
      detuning among the dyad. The stability properties of the identified model match
      the relations observed in the experimental data. In short, our model predicts the
      dynamics of inter-human movement coordination. It can directly be implemented to
      enrich human-robot interaction.

PMID- 22648568
TI  - An optimal control strategy for two-dimensional motion camouflage with non
      holonimic constraints.
AB  - Motion camouflage is a stealth behaviour observed both in hover-flies and in
      dragonflies. Existing controllers for mimicking motion camouflage generate this
      behaviour on an empirical basis or without considering the kinematic motion
      restrictions present in animal trajectories. This study summarises our formal
      contributions to solve the generation of motion camouflage as a non-linear
      optimal control problem. The dynamics of the system capture the kinematic
      restrictions to motion of the agents, while the performance index ensures
      camouflage trajectories. An extensive set of simulations support the technique,
      and a novel analysis of the obtained trajectories contributes to our
      understanding of possible mechanisms to obtain sensor based motion camouflage,
      for instance, in mobile robots.

PMID- 22648569
TI  - The effect of the Ginkgo biloba extract in the expression of Bax, Bcl-2 and bone
      mineral content of Wistar rats with glucocorticoid-induced osteoporosis.
AB  - OBJECTIVE: Evaluate the effects of the extract of Ginkgo biloba (EGb) in the
      glucocorticoid-induced-osteoporosis through the Bax and Bcl-2 expressions by
      osteoblast cells, the x-ray and bone density of the tibia. METHOD: Rats were
      divided into five groups: osteoporosis; EGb1 (28 mg/kg); EGb2 (56 mg/kg);
      alendronate (0.2 mg/animal) and control. The treatments were conducted for 20 (n
      = 30) and 30 days (n = 30). The Bax and Bcl-2 expressions were evaluated in
      osteoblasts of the mandibular alveolar bone. The tibias were radiographed to
      evaluate the X-ray and bone density. The control group was compared with the
      osteoporosis' (Student's t-test/Mann-Whitney). The other groups were analyzed by
      analysis of variance test followed by Dunnett/Dunnett T3 (p < 0.05). RESULTS:
      When compared the osteoporosis to the control group (p <0.05): Bax and x-ray
      density increased; Bcl-2 and the bone density reduced. When compared with the
      osteoporosis group (p < 0.05), alendronate (30 days), EGb1 and EGb2 (20/30 days)
      increased the Bcl-2 expression; EGb2 and alendronate (20 days) EGb1 and EGb2 (30
      days) reduced the Bax expression; and EGb1 and EGb2 (20/30 days) reduced the X
      ray density. CONCLUSIONS: The EGb improved the Bcl-2 and reduced the Bax
      expression by osteoblasts in the mandibular alveolar bone and recovered the
      mineral content in the tibia of rats with glucocorticoid-induced-osteoporosis.

PMID- 22648570
TI  - Diffusion-weighted magnetic resonance imaging in the characterization of axillary
      lymph nodes in patients with breast cancer.
AB  - PURPOSE: To assess prospectively the accuracy of diffusion-weighted magnetic
      resonance imaging (DWI) in differentiating between metastatic and benign axillary
      lymph nodes in patients with breast cancer. MATERIALS AND METHODS: In all, 215
      patients with histologically proven breast cancer, prior to axillary dissection,
      underwent breast and axillary 1.5 T MRI. In 102 patients in whom at least one
      axillary lymph node with a short axis of 6 mm or more was found the apparent
      diffusion coefficient (ADC) was measured in one lymph node per patient by means
      of an echo planar, parallel imaging DWI sequence. Forty-three lymph nodes were
      finally included which, on histological examination, either contained a
      metastasis larger than 5 mm or were metastasis-free; nodes with metastases
      smaller than 5 mm were excluded. RESULTS: From histological examination, 19/43
      lymph nodes had a metastasis at least 5 mm, while in 24/43 no malignant cells
      were found. The ADC values of the lymph nodes with metastases (mean: 0.878 * 10(
      3) mm(2) /s; range: 0.30 -1.20) were significantly lower (P < 0.001) than those
      of the benign lymph nodes (mean: 1.494; range: 0.60 -2.50). Adopting a threshold
      value of 1.09 * 10(-3) mm(2) /s DWI resulted in 94.7% sensitivity, 91.7%
      specificity, and 93.0% accuracy in the identification of metastasis in this
      series of lymph nodes. CONCLUSION: From these preliminary data DWI seems a
      promising method in the differential diagnosis between metastatic and benign
      axillary lymph nodes in patients with breast cancer.

PMID- 22648571
TI  - Gadolinium-induced fibrosis is counter-regulated by CCN3 in human dermal
      fibroblasts: a model for potential treatment of nephrogenic systemic fibrosis.
AB  - We recently show that CCN3 is a counter-regulatory molecule for the pro-fibrotic
      protein CCN2, and a potentially novel fibrosis therapy. The goal of this study
      was to assess the role of CCN3 in fibroproliferative/fibrotic responses in human
      dermal fibroblasts exposed to Omniscan, one of the gadolinium-based contrast
      agents associated with development of nephrogenic systemic fibrosis (NSF) a rare
      but life-threatening disease thought to be complication of NMR diagnostics in
      renal impaired patients. Human dermal fibroblasts were exposed to Omniscan; or to
      platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF
      beta) as controls. Proliferation was assessed along with matrix metalloproteinase
      1, tissue inhibitor of metalloproteinases-1 and type 1 procollagen in the absence
      and presence of CCN3. In parallel, CCN3 production was assessed in control and
      Omniscan-treated cells. The results showed that PDGF stimulated fibroblast
      proliferation, production of Timp-1 and MMP-1 whereas exogenous CCN3 inhibited,
      in a dose response manner, cell proliferation (approx. 50 % max.) and production
      of MMP-1 (approx 35 % max.) but had little effect on TIMP-1. TGF-beta stimulated
      type 1 procollagen production but not proliferation, Timp-1 or MMP-1 compared to
      non-TGF-beta treated control cells, and CCN3 treatment blocked (approx. 80 %
      max.) this up-regulation. Interestingly, untreated, control fibroblasts produced
      high constitutive levels of CCN3 and concentrations of Omniscan that induced
      fibroproliferative/fibrogenic changes in dermal fibroblasts correspondingly
      suppressed CCN3 production. The use of PDGF and TGF-beta as positive controls,
      and the study of differential responses, including that to Omniscan itself,
      provide the first evidence for a role of fibroblast-derived CCN3 as an endogenous
      regulator of pro-fibrotic changes, elucidating possible mechanism(s). In
      conclusion, these data support our hypothesis of a role for fibroblast-derived
      CCN3 as an endogenous regulator of pro-fibrotic changes in these cells, and
      suggest that CCN3 may be an important regulatory molecule in NSF and a target for
      treatment in this and other fibrotic diseases.

PMID- 22648573
TI  - Comparing soil chemistries of leached and nonleached copper-amended soils.
AB  - Leaching metal-spiked samples has been proposed as a means to reduce the
      artifacts of the spiking procedure (e.g., salt effect, increased metal
      solubility) that can artificially increase metal bioaccessibility and toxicity in
      laboratory ecotoxicity tests. The effects on soil chemistry from leaching Cu
      spiked samples were investigated by comparing chemistries of freshly spiked
      samples to samples that underwent the spike/leach procedure. Chemical parameters
      investigated included electrical conductivity (EC), pH,
      ethylenediaminetetraacetic acid- and CaCl(2) -extractable Cu, soil-solution Cu,
      Cu(2+) activity (estimated using Visual MINTEQ), and other solution parameters
      (dissolved organic carbon [DOC], Ca, Mg, Al). In leached samples, the electrical
      conductivity values of the spiked samples did not vary significantly from those
      of the control samples (p > 0.05), confirming that the leaching procedure had
      sufficiently minimized the salt effect. In the range of soil Cu concentrations
      where Cu ecotoxicity is expected, the pH in freshly spiked samples was as much as
      0.52 units lower than the pH from leached samples at the same total-soil Cu
      concentration. The CaCl(2) -extractable fraction was up to 2.3-fold smaller in
      leached samples and inversely related to the pH of the spiked soil. Despite
      little to no difference in soil-solution Cu, up to 100-fold less Cu(2+) activity
      was observed in leached samples. Reduced Cu(2+) activity was related to less
      Al(3+) competition for DOC. Leaching resulted in solution chemistries that were
      more consistent with those of the control samples and reduced the artifacts of
      traditional soil-spiking procedures.

PMID- 22648574
TI  - Trabecular level analysis of bone cement augmentation: a comparative experimental
      and finite element study.
AB  - The representation of cement-augmented bone in finite element (FE) models of
      vertebrae following vertebroplasty remains a challenge, and the methods of the
      model validation are limited. The aim of this study was to create specimen
      specific FE models of cement-augmented synthetic bone at the microscopic level,
      and to develop a new methodology to validate these models. An open cell
      polyurethane foam was used reduce drying effects and because of its similar
      structure to osteoporotic trabecular bone. Cylindrical specimens of the foam were
      augmented with PMMA cement. Each specimen was loaded to three levels of
      compression inside a micro-computed tomography (MUCT) scanner and imaged both
      before compression and in each of the loaded states. Micro-FE models were
      generated from the unloaded MUCT images and displacements applied to match
      measurements taken from the images. A morphological comparison between the FE
      predicted trabecular deformations and the corresponding experimental measurements
      was developed to validate the accuracy of the FE model. The predicted deformation
      was found to be accurate (less than 12% error) in the elastic region. This method
      can now be used to evaluate real bone and different types of bone cements for
      different clinical situations.

PMID- 22648575
TI  - A novel rule-based algorithm for assigning myocardial fiber orientation to
      computational heart models.
AB  - Electrical waves traveling throughout the myocardium elicit muscle contractions
      responsible for pumping blood throughout the body. The shape and direction of
      these waves depend on the spatial arrangement of ventricular myocytes, termed
      fiber orientation. In computational studies simulating electrical wave
      propagation or mechanical contraction in the heart, accurately representing fiber
      orientation is critical so that model predictions corroborate with experimental
      data. Typically, fiber orientation is assigned to heart models based on Diffusion
      Tensor Imaging (DTI) data, yet few alternative methodologies exist if DTI data is
      noisy or absent. Here we present a novel Laplace-Dirichlet Rule-Based (LDRB)
      algorithm to perform this task with speed, precision, and high usability. We
      demonstrate the application of the LDRB algorithm in an image-based computational
      model of the canine ventricles. Simulations of electrical activation in this
      model are compared to those in the same geometrical model but with DTI-derived
      fiber orientation. The results demonstrate that activation patterns from
      simulations with LDRB and DTI-derived fiber orientations are nearly
      indistinguishable, with relative differences <=6%, absolute mean differences in
      activation times <=3.15 ms, and positive correlations >=0.99. These results
      convincingly show that the LDRB algorithm is a robust alternative to DTI for
      assigning fiber orientation to computational heart models.

PMID- 22648576
TI  - A nonlinear constitutive model for stress relaxation in ligaments and tendons.
AB  - A novel constitutive model that describes stress relaxation in transversely
      isotropic soft collagenous tissues such as ligaments and tendons is presented.
      The model is formulated within the nonlinear integral representation framework
      proposed by Pipkin and Rogers (J. Mech. Phys. Solids. 16:59-72, 1968). It
      represents a departure from existing models in biomechanics since it describes
      not only the strain dependent stress relaxation behavior of collagenous tissues
      but also their finite strains and transverse isotropy. Axial stress-stretch data
      and stress relaxation data at different axial stretches are collected on rat tail
      tendon fascicles in order to compute the model parameters. Toward this end, the
      rat tail tendon fascicles are assumed to be incompressible and undergo an
      isochoric axisymmetric deformation. A comparison with the experimental data
      proves that, unlike the quasi-linear viscoelastic model (Fung, Biomechanics:
      Mechanics of Living Tissues. Springer, New York, 1993) the constitutive law can
      capture the observed nonlinearities in the stress relaxation response of rat tail
      tendon fascicles.

PMID- 22648578
TI  - On the estimation of total arterial compliance from aortic pulse wave velocity.
AB  - Total arterial compliance (C(T)) is a main determinant of cardiac afterload, left
      ventricular function and arterio-ventricular coupling. C(T) is physiologically
      more relevant than regional aortic stiffness. However, direct, in vivo, non
      invasive, measurement of C(T) is not feasible. Several methods for indirect C(T)
      estimation require simultaneous recording of aortic flow and pressure waves,
      limiting C(T) assessment in clinical practice. In contrast, aortic pulse wave
      velocity (aPWV) measurement, which is considered as the "gold standard" method to
      assess arterial stiffness, is noninvasive and relatively easy. Our aim was to
      establish the relation between aPWV and C(T). In total, 1000 different
      hemodynamic cases were simulated, by altering heart rate, compliance, resistance
      and geometry using an accurate, distributed, nonlinear, one-dimensional model of
      the arterial tree. Based on Bramwell-Hill theory, the formula C(T) = k * aPWV(-2)
      was found to accurately estimate C(T) from aPWV. Coefficient k was determined
      both analytically and by fitting C(T) vs. aPWV data. C(T) estimation may provide
      an additional tool for cardiovascular risk (CV) assessment and better management
      of CV diseases. C(T) could have greater impact in assessing elderly population or
      subjects with elevated arterial stiffness, where aPWV seem to have limited
      prognostic value. Further clinical studies should be performed to validate the
      formula in vivo.

PMID- 22648579
TI  - Analysis of drug distribution from a simulated drug-eluting stent strut using an
      in vitro framework.
AB  - The mechanisms of delivery of anti-proliferative drug from a drug-eluting stent
      are defined by transport forces in the coating, the lumen, and the arterial wall.
      Dynamic asymmetries in the localized flow about stent struts have previously been
      shown to contribute to significant heterogeneity in the spatial distribution of
      drug in in silico three-compartmental models of stent based drug delivery. A
      novel bench-top experiment has been created to confirm this phenomena. The
      experiment simulates drug release from a single stent strut, and then allows
      visualization of drug uptake into both lumen and tissue domains using optical
      techniques. Results confirm the existence of inhomogeneous and asymmetric
      arterial drug distributions, with this distribution shown to be sensitive to the
      flow field surrounding the strut.

PMID- 22648577
TI  - Multiscale mechanics of articular cartilage: potentials and challenges of
      coupling musculoskeletal, joint, and microscale computational models.
AB  - Articular cartilage experiences significant mechanical loads during daily
      activities. Healthy cartilage provides the capacity for load bearing and
      regulates the mechanobiological processes for tissue development, maintenance,
      and repair. Experimental studies at multiple scales have provided a fundamental
      understanding of macroscopic mechanical function, evaluation of the
      micromechanical environment of chondrocytes, and the foundations for
      mechanobiological response. In addition, computational models of cartilage have
      offered a concise description of experimental data at many spatial levels under
      healthy and diseased conditions, and have served to generate hypotheses for the
      mechanical and biological function. Further, modeling and simulation provides a
      platform for predictive risk assessment, management of dysfunction, as well as a
      means to relate multiple spatial scales. Simulation-based investigation of
      cartilage comes with many challenges including both the computational burden and
      often insufficient availability of data for model development and validation.
      This review outlines recent modeling and simulation approaches to understand
      cartilage function from a mechanical systems perspective, and illustrates
      pathways to associate mechanics with biological function. Computational
      representations at single scales are provided from the body down to the
      microstructure, along with attempts to explore multiscale mechanisms of load
      sharing that dictate the mechanical environment of the cartilage and
      chondrocytes.

PMID- 22648580
TI  - Graphic gambling warnings: how they affect emotions, cognitive responses and
      attitude change.
AB  - The present study focuses on the effects of graphic warnings related to excessive
      gambling. It is based upon a theoretical model derived from both the Protection
      Motivation Theory (PMT) and the Elaboration Likelihood Model (ELM). We focus on
      video lottery terminal (VLT), one of the most hazardous format in the gaming
      industry. Our cohort consisted of 103 actual gamblers who reported previous
      gambling activity on VLT's on a regular basis. We assess the effectiveness of
      graphic warnings vs. text-only warnings and the effectiveness of two major
      arguments (i.e., family vs. financial disruption). A 2 * 2 factorial design was
      used to test the direct and combined effects of two variables (i.e., warning
      content and presence vs. absence of a graphic). It was found that the presence of
      a graphic enhances both cognitive appraisal and fear, and has positive effects on
      the Depth of Information Processing. In addition, graphic content combined with
      family disruptions is more effective for changing attitudes and complying with
      the warning than other combinations of the manipulated variables. It is proposed
      that ELM and PMT complement each other to explain the effects of warnings.
      Theoretical and practical implications are discussed.

PMID- 22648581
TI  - A review of the tragal pointer: anatomy and its importance as a landmark in
      surgical procedures.
AB  - The tragal pointer has long been used as a surgical landmark for the
      identification of the facial nerve trunk and the maxillary artery in such
      procedures as parotidectomy, internal fixation of subcondylar and condylar
      fractures, mandibular  osteotomy, temporomandibular joint arthroplasty, and
      percutaneous  blocks of branches of the trigeminal nerve and pterygopalatine
      ganglion. Aside from its use as an external landmark, it has also been implicated
      as a contributor  to crease formation in the presence of peripheral arterial
      disease. This article will review the available literature on the tragal
      pointer's use as an external  landmark.

PMID- 22648582
TI  - Determination of cerebellar volume in children and adolescents with magnetic
      resonance images.
AB  - Recent studies show that the cerebellum contributes to higher cognitive functions
      as well as its role on motor system. It is thought that higher cognitive
      functions continue to develop during childhood and adolescence; therefore,
      cerebellum develops significantly during these periods. For that reason, this
      study was carried out in order to determine cerebellar volumes of 90 healthy
      individuals (40 males, 50 females) aged between 6 and 17 years according to their
      gender. The individuals were divided into three age groups of 6-9, 10- -13, and
      14-17 years, and their cerebellar volumes were found by means of stereological
      methods using their magnetic resonance images. The cerebellar volumes found were
      compared among the groups without discriminating genders, among groups according
      to gender, and again according to gender within each age group. The general
      average cerebellar volume of the age group 10-13 years was significantly higher
      than the other two age groups(p < 0.05). When the groups were compared according
      to gender, there was no important difference between the groups in women (p >
      0.05); as for men, cerebellar volume only in the age group 10-13 years was
      significantly higher than that in age group 6-9 (p < 0.05). When cerebellar
      volume for ages 6-17 years was compared according to gender (without dividing
      into age group) there was no significant difference between men and women (p >
      0.05). It was seen that the cerebellum develops from childhood to adolescence,
      and reaches peak levels between the ages 10-13 years for both genders.

PMID- 22648583
TI  - Gestational diabetes induced neuronal loss in CA1 and CA3 subfields of rat
      hippocampus in early postnatal life.
AB  - This study was conducted to determine the effect of gestational diabetes on the 
      neuronal density of CA1 and CA3 subfields of the hippocampus in Wistar rat
      offspring.  On day 1 of gestation, 10 dams were randomly allocated into two
      control  and diabetic groups. Five animals in the diabetic group received 40
      mg/kg/b.w. of  streptozotocin (intraperitoneally) and the control animals were
      received normal saline.  Six offspring of each of the gestational diabetics and
      controls were randomly  selected in postnatal days 7 and 21. The infants were
      scarified and coronal sections  were taken from the right dorsal hippocampus and
      stained with cresyl violet. The  number of pyramidal cells per 10000 MUm(2) area
      and the thickness of layers of hippocampus  in CA1 and CA3 were evaluated. In
      postnatal day 7, the number of pyramidal  neurons in CA1 significantly reduced
      from 118.82 +/- 8.0 in the control group to  84.71 +/- 3.3 neurons in gestational
      diabetic group, and in postnatal day 21 it significantly  reduced from 112.71 +/-
      6.9 in the control group to 91.52 +/- 8.5 in the  gestational diabetic group.
      Also, the number of pyramidal cells of CA3 on postnatal  day 7 significantly
      reduced from 90.33 +/- 8.1 in the control group to 62.86 +/- 7.2 in  the
      gestational diabetic group, and in P21 the number of pyramidal cells
      significantly  reduced from 78.33 +/- 2.4 in the control group to 61.7 +/- 9.5
      cells in the diabetic  group. In CA1 and CA3 the thickness of the pyramidal layer
      on postnatal days 7 and  21 non-significantly increased in gestational diabetics
      in comparison with the controls.  This study showed that uncontrolled gestational
      diabetes reduces the pyramidal  neurons of the hippocampus in rat offspring.

PMID- 22648584
TI  - Foramina parietalia permagna: the ins and outs.
AB  - Foramina parietalia permagna or enlarged parietal foramina are a rare variant 
      estimated to be less than 1 in 25,000 cases. Out of 150 dry macerated skulls 
      studied one skull showed 2 large parietal foramina measuring 17.38 x 27.67 mm 
      (right) and 15.31 x 25.46 mm (left) in size. Between them, across the  sagittal
      suture, was a transverse communicating suture interrupted by 3 very  small
      wormian bones. There is no denial of the fact that this familial transmitted 
      trait is caused by erratic ossification due to gene mutations. The clinical 
      importance lies in these being markers for underlying neural or bone pathology 
      or metabolic syndrome. The enlarged parietal foramina as expressed by the  eyes
      at the back remain a curious anatomical but a definite clinico-pathological 
      entity.

PMID- 22648585
TI  - The use of computer-assisted image analysis in measuring the histological
      structure of the human median nerve.
AB  - BACKGROUND AND AIM: The aim of this study was to assess the histological
      structure of the median nerve and its motor branch (number and arrangement of
      nerve bundles) and the cross-sectional area (CSA) of the median nerve (on the
      level of the carpal tunnel). MATERIAL AND METHODS: This study has been conducted
      using median nerves dissected from cadavers stored in a 10% solution of
      formaldehyde at the Department of Anatomy of the Jagiellonian University Medical
      College and cadavers from the Department of Forensic Medicine of the Jagiellonian
      University Medical College. After dissection the median nerves were stained with
      haematoxylin and eosin and histological slides were prepared. These were later
      photographed (16 x magnification) and analysed using ImageJ software. The
      research protocol was approved by the Jagiellonian University Ethics Committee
      (registry KBET/209/B/2002). RESULTS: The studied group comprised 8 women and 22
      men (age between 23-92 years), yielding a total of 60 median nerves (30 right vs.
      30 left). In 4 (6.67%) cases an accessory motor branch was found. The mean CSA of
      the median nerve was 0.19 cm(2). The median nerves from the right hand had a
      statistically larger CSA (p = 0.017). The number of nerve bundles in the median
      nerve varied between 13 to 38 and in the motor branch of the median nerve between
      4 to 14. CONCLUSIONS: The nerve bundles of the median nerve, at the level of the
      carpal tunnel, display no particular type of arrangement. ImageJ software proved
      useful in the assessment of the histological structure of the human median nerve
      and its motor branch.

PMID- 22648586
TI  - Possible usefulness of echocardiographic Z-scores in autopsy routine of the
      foetal great vessels.
AB  - BACKGROUND: Abnormal diameters of foetal vessels are common findings in
      congenital heart defects. However, it is difficult for pathologist to assess
      whether the diameters of the vessels are normal or not and to compare with
      echocardiographic data. The Z-score is a dimensionless quantity representing the
      distance between the raw score and population mean in standard deviation units.
      Using Z-score, we can compare single cases to average standards in the
      population. AIM: To compare diameters of great arteries measured in specimens
      fixed in 10% formalin solution to normal values obtained on echocardiography
      using Z-scores. MATERIAL AND METHODS: The study was performed on 43 formalin
      fixed normal foetal hearts aged from 19 to 40 weeks of gestation. Each specimen
      was dissected and the following diameters were measured: aortic valve (AoV),
      ascending aorta (AAo), descending aorta (DAo), aortic isthmus (AoI), ductus
      arteriosus (DA), pulmonary trunk valve (PV), and pulmonary arteries (RPA and
      LPA). Z-score parameters were calculated for all structures using the Foetal Echo
      Z-score Calculator. RESULTS: Z-score values of all measured foetuses were mostly
      found to fit within the echocardiographic norms, although the most reliable
      results were obtained for foetuses aged 23 weeks. This group was represented by
      the highest number of specimens. The minimal and maximal Z-score values were,
      respectively: AoV -3.45, 1.4; AAo -4.24, -0.11; DAo -2.12, 1.29; PV -3.21, 0.69;
      RPA -3.4, 0.84; LPA -2.25, 0.31; AoI -1.97, 0.96; DA -3.56, -1.52. CONCLUSIONS:
      The diameters of great arteries measured on autopsy are comparable to the results
      obtained from echocardiographic measurement. Z-score values for foetal
      echocardiography can be applied to post-mortem examination.

PMID- 22648587
TI  - Morphometry of the coronary artery and heart microcirculation in infants.
AB  - Knowledge of morphometric quantities of coronary arteries in infants is an 
      increasingly vital component in managing congenital and acquired heart disease. 
      Because of considerable heterogeneity of coronary vasculature, what is 
      considered atypical and aberrant or insignificant anatomy is often unclear. The 
      purpose of our present study is to define normal infant anatomy. This was  done
      by focusing on the segment analysis of coronary arteries in infants. Segment 
      analysis was used to define an accurate definition of the length and  diameter of
      the coronary network. The lengths, widths, and numbers of collateral  branches of
      the coronary arteries were measured. The coronary vessels of  40 infant hearts
      were visualised postmortem by injection of the coronary arteries  with X-ray
      opaque dye for the imaging study. Also, black ink cast and silver  impregnation
      specimens were studied. The longest segment of the circumflex  branches of left
      coronary arteries was the second; the lengths were 9066.6 +/-  +/- 1828 MUm. The
      length of I, III, and IV were 7366 +/- 378.7 MUm, 7536.6 +/-  +/- 1533.8 MUm,
      4476.6 +/- 690.9 MUm, respectively. The lengths of the circumflex  branch of the
      coronary artery were longer than that of the others; it is joined  with the
      anterior interventricular branch of the coronary artery in the dorsal  wall of
      the left ventricle. Rates of branching and ramification were low, and  the number
      of lateral branches was low.

PMID- 22648588
TI  - Anatomical analysis of preangular mandibular notch in humans.
AB  - The authors have analysed in detail the mandibular preangular notch on the  basis
      of 273 human cadaver mandibles. They have revealed that the pregonial  notch is
      present in almost 90% of cases and that it is generally asymmetric and 
      elliptical in shape. The depth and length of the anterior part of the notch is 
      greater in males. Moreover, the preangular notch depth is greater on the right 
      side (regardless of sex). Knowledge of the preangular notch anatomy can be 
      useful for surgeons during reconstructive and plastic procedures on the
      mandibular  shaft.

PMID- 22648589
TI  - Estimation of nasal cavity and conchae volumes by stereological method.
AB  - BACKGROUND: Studies evaluating the mean volumes of nasal cavity and concha are
      very rare. Since there is little date on the mentioned topic, we aimed to carry
      out the presented study to obtain a volumetric index showing the relation between
      the nasal cavity and concha. MATERIAL AND METHODS: The volumes of the nasal
      cavity and concha were measured in 30 males and 30 females (18-40 years old) on
      computed tomography images using stereological methods. RESULTS: The mean volumes
      of nasal cavity, concha nasalis media, and concha nasalis inferior were 5.95 +/-
      0.10 cm(3), 0.56 +/- 0.22 cm(3), and 1.45 +/- 0.68 cm(3); 7.01 +/- 0.18 cm(3),
      0.67 +/- 0.31 cm(3) and 1.59 +/- 0.98 cm(3) in females and males, respectively.
      There were statistically significant differences in the volume of the nasal
      cavity and concha nasalis media (p < 0.05) between males and females, except for
      concha nasalis inferior (p > 0.05). CONCLUSIONS: Our results could provide
      volumetric indexes for the nasal cavity and concha, which could help the
      physician to manage surgical procedures related to the nasal cavity and concha.

PMID- 22648590
TI  - Matrix change of bone grafting substitute after implantation into guinea pig
      bulla.
AB  - BACKGROUND: Many different surgical techniques have been developed to remove open
      mastoid cavities. In addition to autologous materials, alloplastic substances
      have been used. A very slow absorption of these materials and extrusion reactions
      have been reported. We investigated a newly developed, highly porous bone
      grafting material to eliminate open mastoid cavities, in an animal model. To
      characterise the transformation process, the early tissue reactions were studied
      in relation to the matrix transformation of the bone material. MATERIAL AND
      METHODS: NanoBone (NB), a highly porous bone grafting material based on calcium
      phosphate and silica, was filled into the open bullae from 20 guinea pigs. The
      bullae were examined histologically. Energy dispersive X-ray spectroscopy (EDX)
      was used to investigate the change in the elemental composition at different
      sampling times. The surface topography of the sections was examined by electron
      microscopy. RESULTS: After 1 week, periodic acid-Schiffs (PAS) staining
      demonstrated accumulation of glycogen and proteins, particularly in the border
      area of the NB particles. After 2 weeks, the particles were evenly coloured after
      PAS staining. EDX analysis showed a rapid absorption of the silica in the bone
      grafting material. CONCLUSIONS: NanoBone showed a rapid matrix change after
      implantation in the bullae of guinea pigs. The absorption of the silica matrix
      and replacement by PAS-positive substances like glycoproteins and
      mucopolysaccharides seems to play a decisive role in the degradation processes of
      NB. This is associated with the good osteoinductive properties of the material.

PMID- 22648591
TI  - Partial anomalous pulmonary venous return associated with vascular anomalies of
      the aorta: multidetector computed tomography findings.
AB  - Partial anomalous pulmonary venous return (PAPVR) is a congenital anomaly that 
      involves drainage of one to three pulmonary veins directly into the right heart
      or  systemic venous system, creating a partial left-to-right shunt. This drainage
      is associated  with cardiac abnormalities such as mitral stenosis and pulmonary
      stenosis,  patent ductus arteriosus, and atrial septal defects. We report a case
      of PAPVR  associated with vascular anomalies of the aorta by multidetector
      computed tomography  in an adult female patient.

PMID- 22648592
TI  - The trifid superior transverse scapular ligament: a case report and review of the
      literature.
AB  - During dissection of a 75-year-old Caucasian female cadaver, a trifid superior 
      transverse scapular ligament (STSL) was found. The suprascapular nerve and 
      vessels ran inferior to the STSL though the suprascapular notch. Measurements  of
      the structures of the suprascapular region were taken using two complementary 
      but independent methods: a classical method using an electronic digimatic 
      calliper and a new one based on an analysis of digital photographic 
      documentation of the STSL. The knowledge of anatomic variations of the STSL  is
      important because this structure is the most commonly recognised possible 
      predisposing factor of suprascapular nerve entrapment and can be helpful in 
      diagnosis and surgical and arthroscopic treatment of this pathology.

PMID- 22648593
TI  - Unilateral high origin of radial artery from axillary artery.
AB  - Variations in the vascular system of upper limbs are relatively common, with 
      considerable significance towards the clinical and surgical point of view.  The
      major arterial variations reported are of high origins of radial and ulnar 
      arteries. During routine dissection of an upper extremity in the Department  of
      Anatomy, Medical University of the Americas, Nevis, West Indies, a variation  in
      the origin of the radial artery from the axillary artery was observed in  the
      right upper limb of a 55-year-old female cadaver. The normal and variant  origin
      of the radial artery has pragmatic importance for surgeons and  radiologists.
      Also, the superficial position of an artery makes it vulnerable to  injury during
      cannulation, which may lead to pseudoaneurysm.

PMID- 22648594
TI  - Bony spurs projecting in the obturator foramen.
AB  - The obturator foramen is large oval aperture in males or irregularly triangular 
      aperture in females in the hipbone, situated anteroinferior to the acetabulum 
      between the pubis and ischium. The dry bone under study is a male left sided 
      hipbone. It contains the obturator groove through which the obturator nerve  and
      vessels pass. During analysis of hipbones in the osteology laboratory of  CSM
      Medical University Lucknow, UP, India, a hipbone was found in which  bony spurs
      or exostoses were projecting from the margins into the obturator  foramen. These
      bony projections in the obturator foramen constitute a new  anatomical variant in
      the hipbone, as they have not been reported before.  These bony spurs may impinge
      on the obturator nerve and vessels causing  neurovascular complications and also
      trauma to the soft tissues during biomechanical  movements. In addition, these
      bony spurs may cause spasms of the  obturator internus and externus muscles,
      causing groin pain. These bony projections  may also lead to misinterpretation of
      radiographs. Thus, knowledge of  these bony spurs is of paramount importance to
      anatomists, surgeons, sport  physicians, and radiologists.

PMID- 22648595
TI  - In vitro modifications of the scala tympani environment and the cochlear implant
      array surface.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the influence of alterations of the scala
      tympani environment and modifications of the surface of cochlear implant
      electrode arrays on insertion forces in vitro. STUDY DESIGN: Research
      experimental study. METHODS: Fibroblasts producing neurotrophic factors were
      cultivated on the surface of Nucleus 24 Contour Advance electrodes. Forces were
      recorded by an Instron 5542 Force Measurement System as three modified arrays
      were inserted into an artificial scala tympani model filled with phosphate
      buffered saline (PBS). The recorded forces were compared to control groups
      including three unmodified electrodes inserted into a model filled with PBS
      (unmodified environment) or Healon (current practice). Fluorescence microscopy
      was used before and after the insertions to identify any remaining fibroblasts.
      Additionally, three Contour Advance electrodes were inserted into an artificial
      model, filled with alginate/barium chloride solution at different concentrations,
      while insertion forces were recorded. RESULTS: Modification of the scala tympani
      environment with 50% to 75% alginate gel resulted in a significant decrease in
      the insertion forces. The fibroblast-coated arrays also led to decreased forces
      comparable to those recorded with Healon. Fluorescence microscopy revealed fully
      cell-covered arrays before and partially covered arrays after the insertion; the
      fibroblasts on the arrays' modiolar surface remained intact. CONCLUSIONS:
      Modifications of the scala tympani's environment with 50% to 75% alginate/barium
      chloride and of the cochlear implant electrode surface with neurotrophic factor
      producing fibroblasts drastically reduce the insertion forces. As both
      modifications may serve future intracochlear therapies, it is expected that these
      might additionally reduce possible insertion trauma.

PMID- 22648596
TI  - Congenital agenesis of all the nasal cartilages.
AB  - With the exception of septal deviation, congenital anomalies of the nasal
      cartilages constitute a small fraction of all congenital nasal anomalies. This
      report presents a patient with isolated agenesis of all the nasal cartilages,
      which has never been recorded previously. 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- 22648597
TI  - Hypoplastic lateral crus causing alar retraction and underprojected nasal tip:
      correction with multiple grafts.
AB  - A case of severe alar retraction and underprojected nasal tip due to hypoplastic
      lateral crura was successfully treated using a columellar strut graft, lateral
      crus replacement graft, and lateral crus caudalization graft and Medpor implant.
      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 at www.springer.com/00266.

PMID- 22648598
TI  - The effects of aesthetic breast augmentation on quality of life, psychological
      distress, and eating disorder symptoms: a prospective study.
AB  - BACKGROUND: There are only a few studies that provide sufficient data regarding
      the effects of aesthetic breast augmentation on various aspects of quality of
      life. Significant improvement in body image, satisfaction with appearance, sexual
      attractiveness, and self-esteem has been observed in these studies. In contrast,
      however, a somewhat impaired general health-related quality of life has been
      reported at follow-up. Nevertheless, when considering the effects of aesthetic
      breast augmentation on eating habits, publications are lacking. We therefore
      decided to assess the effects of aesthetic breast augmentation on quality of
      life, psychological distress, and eating disorder symptoms. METHODS: This study
      included 79 consecutive women who underwent bilateral aesthetic augmentation
      mammaplasty. The women completed three outcome measures at baseline and at follow
      up: the Eating Disorder Inventory, Raitasalo's modification of the Beck
      Depression Inventory, and the 15D general quality-of-life questionnaire. RESULTS:
      The mean age at baseline was 35 years (range = 18-52). The mean body mass index
      was 21.3 (range = 17.5-27.3). Sixty-five (82 %) women completed the outcome
      measures with a mean follow-up time of 7 months (range = 4-13). A significant
      improvement was observed in self-esteem and depression scores as well as body
      satisfaction from baseline to follow-up. Interpersonal trust also improved, and
      after the operation the women were more able to tolerate and understand their own
      feelings and sensations. A significant decrease in the overall risk for an eating
      disorder was also noted. CONCLUSIONS: Aesthetic breast augmentation results in
      significant improvement in women's body satisfaction and self-esteem. The level
      of risk for an eating disorder is also significantly reduced. LEVEL OF EVIDENCE
      III: This journal requires that authors assign a level of evidence to each
      article.

PMID- 22648599
TI  - Scattering of light by plasmonic nanoparticles on a silicon substrate.
AB  - We introduce an effective refractive-index model to predict the spectral
      positions of localized surface plasmon (LSP) modes of a silver nanoparticle on a
      thin-film silicon substrate using a semi-analytical method. The enhanced
      scattering into the substrate caused by the nanoparticle dipole and quadrupole
      modes is verified by comparing theoretical and simulation results. We suggest
      that the LSP modes can be tuned linearly with the thickness of the silicon
      substrate and the size of the nanoparticles. These findings provide simple and
      important physical insights for optimizing the absorption in a thin-film silicon
      solar cell by tuning the LSP modes of the nanoparticles deployed on the surface.

PMID- 22648601
TI  - Pilot prognostic model of extremely poor survival among high-risk hepatocellular
      carcinoma patients.
AB  - BACKGROUND: Populations with low income, economic barriers, and cultural and/or
      linguistic access barriers to medical care are at risk for worse cancer-related
      outcomes. Medically underserved patients with hepatocellular carcinoma (HCC) have
      decreased survival compared with those in the Surveillance, Epidemiology, and End
      Results database. Given this suboptimal outcome, the high cost of HCC treatment,
      and unknown risk-to-benefit ratios of invasive therapies, the authors sought to
      identify a predictive model of extremely poor overall survival (OS). METHODS: A
      retrospective review of an institutional HCC database was conducted. Payor
      status, race, treatment, clinicopathologic, and outcome parameters were recorded.
      The primary outcome was OS <1 month. A logistic regression model predictive of OS
      <1 month was developed using backward, stepwise elimination and bootstrapping
      techniques. RESULTS: In total, 337 patients HCC (272 men and 65 women) were
      identified. Only 4% of patients had Medicare coverage; whereas 96% relied on
      publicly funded, safety-net health programs. OS <1 month was noted in 90 patients
      (26.7%). There were no differences in race or sex between patients who had an OS
      <1 month and those with an OS >1 month. A higher percentage of patients who had
      an OS <1 month had advanced stage disease and did not receive therapy for HCC.
      Advanced liver disease, as measured by laboratory parameters and a composite
      score (Child-Pugh and Model for End-Stage Liver Disease [MELD]), alpha
      fetoprotein level, creatinine level, disease stage, and lack of treatment were
      predictors of OS <1 month. CONCLUSIONS: Survival for medically underserved
      patients with HCC remains poor. Advanced clinical stage and liver disease appear
      to preclude treatment, and novel methods to identify those who may benefit from
      palliative care/symptom control may be indicated for patients who are predicted
      to have poor survival.

PMID- 22648600
TI  - Tunable patterning of microparticles and cells using standing surface acoustic
      waves.
AB  - We have developed an acoustic-based tunable patterning technique by which
      microparticles or cells can be arranged into reconfigurable patterns in
      microfluidic channels. In our approach, we use pairs of slanted-finger
      interdigital transducers (SFITs) to generate a tunable standing surface acoustic
      wave field, which in turn patterns microparticles or cells in one- or two
      dimensional arrays inside the microfluidic channels--all without the assistance
      of fluidic flow. By tuning the frequency of the input signal applied to the
      SFITs, we have shown that the cell pattern can be controlled with tunability of
      up to 72%. This acoustic-based tunable patterning technique has the advantages of
      wide tunability, non-invasiveness, and ease of integration to lab-on-a-chip
      systems, and shall be valuable in many biological and colloidal studies.

PMID- 22648602
TI  - Microglia/monocytes with NG2 expression have no phagocytic function in the cortex
      after LPS focal injection into the rat brain.
AB  - While OX42(+) microglia/macrophages have been considered as a scavenger in the
      brain, NG2(+) cells are generally considered as oligodendrocyte progenitor cells
      or function-unknown glial cells. Recent evidence showed that under some
      pathological conditions, certain cells have become positive for both anti-NG2 and
      anti-OX42 antibodies. Our results suggested that some OX42(+) microglia or
      macrophages were induced to express NG2 proteins 3 and 5 days later after focal
      injection of lipopolysaccharide into the brain cortex of Sprague-Dawley rats. In
      consideration of the induction of NG2 expression may associate with gaining or
      losing functions of microglia/macrophages, we further showed that, while OX42(+)
      or ED1(+) microglia/macrophages presented active phagocytic function, NG2(+)
      /OX42(+) cells failed to engulf latex beads. The induced expression of NG2
      protein may possibly indicate the functional diversity of activated
      microglia/macrophages in the brain.

PMID- 22648603
TI  - Visibility versus accountability in pooling local motion signals into global
      motion direction.
AB  - The human observer is surprisingly inaccurate in discriminating proportions
      between two spatially overlapping sets of randomly distributed elements moving in
      opposite directions. It was shown that observers took into account an equivalent
      of 74 % of all moving elements when the task was to estimate their relative
      number, but only an equivalent of 21 % of the same elements when the task was to
      discriminate between opposite directions. It was concluded that, in the motion
      direction discrimination task, a large proportion of the signal from all of the
      elements was inaccessible to the observers, whereas the majority of the signal
      was accessible in a numerosity task. This type of perceptual limitation belongs
      to the attentional blindness category, where a strong sensory signal cannot be
      noticed when processing is diverted by parallel events. In addition, we found no
      evidence for the common-fate principle, as the ability to discriminate numerical
      proportions remained the same, irrespective of whether all estimated elements
      were moving coherently in one direction or unpredictably in opposite directions.

PMID- 22648604
TI  - Does crossmodal correspondence modulate the facilitatory effect of auditory cues
      on visual search?
AB  - The "pip-and-pop effect" refers to the facilitation of search for a visual target
      (a horizontal or vertical bar whose color changes frequently) among multiple
      visual distractors (tilted bars also changing color unpredictably) by the
      presentation of a spatially uninformative auditory cue synchronized with the
      color change of the visual target. In the present study, the visual stimuli in
      the search display changed brightness instead of color, and the crossmodal
      congruency between the pitch of the auditory cue and the brightness of the visual
      target was manipulated. When cue presence and cue congruency were randomly varied
      between trials (Experiment 1), both congruent cues (low-frequency tones
      synchronized with dark target states or high-frequency tones synchronized with
      bright target states) and incongruent cues (the reversed mapping) facilitated
      visual search performance equally, relative to a no-cue baseline condition.
      However, when cue congruency was blocked and the participants were informed about
      the pitch-brightness mapping in the cue-present blocks (Experiment 2),
      performance was significantly enhanced when the cue and target were crossmodally
      congruent as compared to when they were incongruent. These results therefore
      suggest that the crossmodal congruency between auditory pitch and visual
      brightness can influence performance in the pip-and-pop task by means of top-down
      facilitation.

PMID- 22648605
TI  - Capture of the gaze does not capture the mind.
AB  - Sudden visual changes attract our gaze, and related eye movement control requires
      attentional resources. Attention is a limited resource that is also involved in
      working memory--for instance, memory encoding. As a consequence, theory suggests
      that gaze capture could impair the buildup of memory respresentations due to an
      attentional resource bottleneck. Here we developed an experimental design
      combining a serial memory task (verbal or spatial) and concurrent gaze capture by
      a distractor (of high or low similarity to the relevant item). The results cannot
      be explained by a general resource bottleneck. Specifically, we observed that
      capture by the low-similar distractor resulted in delayed and reduced saccade
      rates to relevant items in both memory tasks. However, while spatial memory
      performance decreased, verbal memory remained unaffected. In contrast, the high
      similar distractor led to capture and memory loss for both tasks. Our results
      lend support to the view that gaze capture leads to activation of irrelevant
      representations in working memory that compete for selection at recall.
      Activation of irrelevant spatial representations distracts spatial recall,
      whereas activation of irrelevant verbal features impairs verbal memory
      performance.

PMID- 22648606
TI  - Using PPT to account for randomness in perception.
AB  - According to many theories of decision making, of which signal detection theory
      is the most prominent, randomness is the main factor responsible for imperfect
      performance. These theories imply that correcting for attenuation due to
      randomness should result in perfect scores as long as the participants use
      nonextreme decision criteria. On the basis of a recent advance termed potential
      performance theory (Trafimow & Rice, Psychological Review 115:447-462, 2008), we
      performed auditory and visual detection experiments and corrected the scores for
      attenuation. Most participants in both experiments tended to perform at a less
      than-perfect level, even after their scores were corrected. The findings
      demonstrate that at least one systematic factor influences detection that is not
      included in signal detection theory.

PMID- 22648608
TI  - Post deployment care for returning combat veterans.
AB  - Since September 11, 2001, 2.4 million military personnel have deployed to Iraq
      and Afghanistan. To date, roughly 1.44 million have separated from the military
      and approximately 772,000 of these veterans have used VA health care. Combat
      deployments impact the physical, psychological, and social health of veterans.
      Given that many veterans are receiving care from non-VA providers, it is
      important that all community health care workers be familiar with the unique
      health care needs of this patient population, which include injuries associated
      with blast exposures (including mild traumatic brain injury), as well as a
      variety of mental health conditions, such as post-traumatic stress disorder.
      Other important health concerns are chronic musculoskeletal pain, medically
      unexplained symptoms, sequelae of environmental exposures, depression, suicide,
      substance abuse, sleep disturbances, and impairments in family, occupational and
      social functioning. Elevated rates of hypertension and tobacco use remind us that
      deployment may result not only in immediate impacts on health, but also increase
      risk for chronic disease, contributing to a growing public health burden. This
      paper provides a comprehensive review of these health concerns and offers
      practical management guidelines for primary care providers. In light of
      relationships between physical, psychological and psychosocial concerns in this
      population, we recommend an interdisciplinary approach to care directed toward
      mitigating the long-term health impacts of combat.

PMID- 22648611
TI  - Metabonomic study of genkwa flos-induced hepatotoxicity and effect of herb
      processing procedure on toxicity.
AB  - A urinary metabonomic approach based on ultraperformance liquid chromatography
      coupled with mass spectrometry (UPLC-MS) was developed to study the metabolic
      disturbances caused by the administration of Genkwa Flos (GF) to rats. Potential
      biomarkers of GF-induced toxic effects were screened out and identified, and the
      underlying toxicological mechanism as well as the detoxification of vinegar
      processing procedure on this herb was discussed. Urine samples were analyzed by
      the established UPLC-MS method. With the help of serum biochemistry and
      histopathology results, metabolic disturbances induced by the exposure to GF and
      the detoxification of processing procedure were confirmed. The differences in the
      metabolic profiles of healthy and treated rats were clearly discriminated with
      the principal component analysis of the chromatographic data. Eight significantly
      changed metabolites were identified and interpreted as biomarkers for the
      hepatotoxicity and detoxification of processing procedure. This study indicated
      that a UPLC-MS-based metabonomic analysis of urine samples could be considered as
      a promising tool to predict the hepatotoxicity induced by the GF and the
      detoxification of traditional vinegar-processing procedure on this herb.

PMID- 22648609
TI  - Does health information exchange reduce unnecessary neuroimaging and improve
      quality of headache care in the emergency department?
AB  - BACKGROUND: Health information exchange (HIE) is advocated as an approach to
      reduce unnecessary testing and improve quality of emergency department (ED) care,
      but little evidence supports its use. Headache is a specific condition for which
      HIE has theoretical benefits. OBJECTIVE: To determine whether health information
      exchange (HIE) reduces potentially unnecessary neuroimaging, increases adherence
      with evidence-based guidelines, and decreases costs in the emergency department
      (ED) evaluation of headache. DESIGN: Longitudinal data analysis SUBJECTS: All
      repeat patient-visits (N = 2,102) by all 1,252 adults presenting with headache to
      a Memphis metropolitan area ED two or more times between August 1, 2007 and July
      31, 2009. INTERVENTION: Use of a regional HIE connecting the 15 major adult
      hospitals and two regional clinic systems by authorized ED personnel to access
      the patient's record during the time period in which the patient was being seen
      in the ED. MAIN MEASURES: Diagnostic neuroimaging (CT, CT angiography, MRI or MRI
      angiography), evidence-based guideline adherence, and total patient-visit
      estimated cost. KEY RESULTS: HIE data were accessed for 21.8 % of ED patient
      visits for headache. 69.8 % received neuroimaging. HIE was associated with
      decreased odds of diagnostic neuroimaging (odds ratio [OR] 0.38, confidence
      interval [CI] 0.29-0.50) and increased adherence with evidence-based guidelines
      (OR 1.33, CI 1.02-1.73). Administrative/nursing staff HIE use (OR 0.24, CI 0.17
      0.34) was also associated with decreased neuroimaging after adjustment for
      confounding factors. Overall HIE use was not associated with significant changes
      in costs. CONCLUSIONS: HIE is associated with decreased diagnostic imaging and
      increased evidence-based guideline adherence in the emergency evaluation of
      headache, but was not associated with improvements in overall costs. Controlled
      trials are needed to test whether specific HIE enhancements to increase HIE use
      can further reduce potentially unnecessary diagnostic imaging and improve
      adherence with guidelines while decreasing costs of care.

PMID- 22648612
TI  - Total laparoscopic partial pancreatoduodenectomy and reconstruction via
      laparoscopic pancreatogastrostomy.
AB  - INTRODUCTION: Minimally invasive surgery has conquered almost all niches of
      abdominal surgery. Even though some surgeons have shown equal lymph node ratio
      and oncologic radicality for laparoscopic surgery of pancreatic cancer, oncologic
      surgeons still take reasonably conservative views of the use of minimally
      invasive techniques for the treatment of pancreatic cancer, especially if located
      in the head of the pancreas. Laparoscopic abdominal approaches on the other hand
      have a potential advantage of better visualization, decreased postoperative pain,
      decreased use of analgetics, and shorter hospital stay. We demonstrate in this
      technical surgical report the first description of a total laparoscopic
      pancreatoduodenectomy and reconstruction via laparoscopic pancreatogastrostomy in
      a 74-year-old female patient with a periampullary tumor. DISCUSSION: After
      pylorus-preserving pancreatoduodenectomy by superior mesenteric artery, first
      approach including standard lymphadenectomy, the reconstruction involved total
      laparoscopic end-to-side running-suture hepaticojejunostomy, double-layer running
      suture antecolic pylorojejunostomy to the first jejunal loop, and
      pancreatogastrostomy via posterior gastrotomy secured by two anchoring and purse
      string sutures.

PMID- 22648613
TI  - Characterization, fine mapping and expression profiling of Ragged leaves1 in
      maize.
AB  - The Ragged leaves1 (Rg1) maize mutant frequently develops lesions on leaves, leaf
      sheaths, and ear bracts. Lesion formation is independent of biotic stress. High
      level accumulation of H(2)O(2) revealed by staining Rg1 leaves, with 3',3'
      diaminobenzidine and trypan blue, suggested that lesion formation appeared to be
      due to cell death. Rg1 was initially mapped to an interval around 70.5 Mb in bin
      3.04 on the short arm of chromosome 3. Utilizing 15 newly developed markers, Rg1
      was delimitated to an interval around 17 kb using 16,356 individuals of a BC1
      segregating population. There was only one gene, rp3, predicted in this region
      according to the B73 genome. Analysis of transcriptome data revealed that 441
      genes significantly up-regulated in Rg1 leaves were functionally over
      represented. Among those genes, several were involved in the production of
      reactive oxygen species (ROS). Our results suggested that lesions of Rg1 maize
      arose probably due to an aberrant rust resistance allele of Rp3, which elicited
      the accumulation of ROS independent of biotic stress.

PMID- 22648615
TI  - The effect of taurine on cholesterol metabolism.
AB  - The elevated plasma cholesterol level, in particular, LDL cholesterol is regarded
      as an important risk factor for the development of atherosclerosis and coronary
      artery disease. A number of studies provide the evidence that taurine has the
      efficient action to reduce plasma and liver cholesterol concentrations,
      especially to decrease VLDL and LDL cholesterol in hypercholesterolemia animal
      induced by high cholesterol diet. Cholesterol lowering effect of taurine is
      actually involved in the regulatory mechanism of cholesterol and bile acid
      homeostasis that mediated by CYP7A1, which has become a biomarker for cholesterol
      metabolism and itself is also regulated by several factors and nuclear receptors.
      This review summarizes the change of cholesterol concentration in metabolism
      observed in feeding studies of hypercholesterolemia animal dealing with taurine,
      and then, addresses the possible metabolic and molecular mechanisms of
      cholesterol lowering effect by taurine in three aspects, cholesterol clearance
      from blood circulation, bioconversion of cholesterol to bile acid in liver, and
      excretion of cholesterol and bile acid from intestine.

PMID- 22648616
TI  - Molecular mechanism of curcumin on the suppression of cholesterol accumulation in
      macrophage foam cells and atherosclerosis.
AB  - SCOPE: Curcumin, a potent antioxidant extracted from Curcuma longa, confers
      protection against atherosclerosis, yet the detailed mechanisms are not fully
      understood. In this study, we examined the effect of curcumin on lipid
      accumulation and the underlying molecular mechanisms in macrophages and
      apolipoprotein E-deficient (apoE-/-) mice. METHODS AND RESULTS: Treatment with
      curcumin markedly ameliorated oxidized low-density lipoprotein (oxLDL)-induced
      cholesterol accumulation in macrophages, which was due to decreased oxLDL uptake
      and increased cholesterol efflux. In addition, curcumin decreased the protein
      expression of scavenger receptor class A (SR-A) but increased that of ATP-binding
      cassette transporter (ABC) A1 and had no effect on the protein expression of
      CD36, class B receptor type I (SR-BI), or ATP-binding cassette transporter G1
      (ABCG1). The downregulation of SR-A by curcumin was via ubiquitin-proteasome
      calpain-mediated proteolysis. Furthermore, the curcumin-induced upregulation of
      ABCA1 was mainly through calmodulin-liver X receptor alpha (LXRalpha)-dependent
      transcriptional regulation. Curcumin administration modulated the expression of
      SR-A, ABCA1, ABCG1, and SR-BI in aortas and retarded atherosclerosis in apoE-/-
      mice. CONCLUSION: Our findings suggest that inhibition of SR-A-mediated oxLDL
      uptake and promotion of ABCA1-dependent cholesterol efflux are two crucial events
      in suppression of cholesterol accumulation by curcumin in the transformation of
      macrophage foam cells.

PMID- 22648617
TI  - Lycopene induces retinoic acid receptor transcriptional activation in mice.
AB  - SCOPE: Lycopene is a lipophilic carotenoid and provides the red colour to
      tomatoes and tomato product. Various studies indicated that lycopene and
      tomatoes/tomato products are able to positively influence various diseases
      associated with a chronic inflammation. The mechanism of action of lycopene to
      elicit these effects is partly unknown. A possible mechanism is that biological
      metabolites of lycopene may activate nuclear hormone receptors in mammalian
      cells. The aim of this study was to investigate the potential of orally
      administered lycopene and all-trans retinoic acid (ATRA) for the induction of the
      retinoic acid receptor (RAR) in a transgenic retinoic acid response-element
      (RARE)-reporter mouse system. METHODS AND RESULTS: Orally administered lycopene
      (100 mg/kg bw in beadlets, n = 6) and ATRA as an endogenous RAR ligand (50 mg/kg
      bw, n = 6) for the induction of the retinoic acid receptor in male mice using a
      transgenic RARE-reporter mouse system. CONCLUSION: Lycopene treatments induced
      RARE-mediated cell signalling indicated by quantified bioimaging, increased
      luciferase activity and up-regulated the retinoid target genes in selected organs
      of the mice. We conclude that lycopene can induce RAR-transcriptional activation
      in mice and lycopene might be a precursor of still non-identified biologically
      active metabolites.

PMID- 22648618
TI  - Annatto prevents retinal degeneration induced by endoplasmic reticulum stress in
      vitro and in vivo.
AB  - SCOPE: Annatto (Bixa orellana) seeds have been used as a colorant in butter and
      in a variety of other foods. In this study, we investigated the amelioration of
      retinal damage by an acetone extract of annatto (A-ext.), bixin (a main component
      of annatto), and four bixin derivatives (Bx-1, Bx-2, Bx-3, and Bx-4) that we have
      synthesized. METHODS AND RESULTS: We used cultured retinal ganglion cells (RGC-5)
      to examine in vitro effects of A-ext. on stress pathways, focusing on
      intracellular oxidation induced by reactive oxygen species, expression of
      endoplasmic reticulum (ER) stress-related proteins, caspase-3 activation, and
      cell membrane damage. In vivo retinal damage in mice following intravitreous
      injection of tunicamycin was evaluated by counting the cell numbers in the
      ganglion cell layer (GCL) and measuring the thickness of outer nuclear layer
      (ONL). A-ext., bixin, and Bx-1 treatment inhibited both tunicamycin- and H2O2
      induced cell death. Bixin derivatives also inhibited tunicamycin-induced cell
      death. Treatment with A-ext., bixin, and Bx-1 reduced tunicamycin-induced caspase
      3 activity and inhibited the inversion of phosphatidylserine, an early apoptotic
      event without antioxidant effect or reduction of ER stress itself. A-ext., bixin,
      and Bx-1 significantly inhibited the tunicamycin-induced loss of cells from the
      GCL, and these materials also suppressed the tunicamycin-induced thinning of ONL.
      CONCLUSION: A-ext., its main component bixin, and bixin derivatives may therefore
      be useful for preventive and therapeutic treatment of retinal-related diseases.

PMID- 22648619
TI  - Lycopene attenuates LPS-induced TNF-alpha secretion in macrophages and
      inflammatory markers in adipocytes exposed to macrophage-conditioned media.
AB  - SCOPE: Adipose tissue is infiltrated by an increasing number of macrophages
      during the development of obesity. These immune cells are suspected to be a major
      source of TNF-alpha that interferes with adipocyte function. Because lycopene
      possesses anti-inflammatory properties, we hypothesize that lycopene could reduce
      the production of TNF-alpha by macrophages and thus interfere in the cross-talk
      between macrophages and adipocytes. METHODS AND RESULTS: We demonstrated that
      physiological concentrations of lycopene were able to attenuate the
      lipopolysaccharide (LPS)-mediated induction of TNF-alpha in RAW 264.7
      macrophages, at both the mRNA and protein levels. The molecular mechanism was
      studied. It appeared that the LPS-activation of both JNK and NF-kappaB signaling
      pathways was modulated by lycopene. The anti-inflammatory effects of lycopene on
      macrophages were accompanied by a decrease in LPS-stimulated macrophage migration
      in the presence of lycopene. Furthermore, lycopene decreased macrophage
      conditioned medium-induced proinflammatory cytokine, acute phase protein, and
      chemokine mRNA expression in 3T3-L1 adipocytes. CONCLUSION: These data indicate
      that lycopene displayed an anti-inflammatory effect on macrophages that
      beneficially impacted adipocyte function. Thus, these results suggest that
      lycopene could block the vicious cycle that occurs between adipocytes and
      macrophages in adipose tissue during obesity.

PMID- 22648620
TI  - Squalene ameliorates atherosclerotic lesions through the reduction of CD36
      scavenger receptor expression in macrophages.
AB  - SCOPE: Anti-atherogenic features of olive oil (OO) have been attributed, in part,
      to minor compounds, via diverse mechanisms, although its effects on the CD36
      receptor have not been examined. We investigated the effects of minor compounds
      of OO (squalene (SQ), tyrosol (Tyr) and hydroxytyrosol (OH-Tyr)), on the
      expression of the CD36 receptor, as well as on monocyte/macrophage
      differentiation and proliferation. METHODS AND RESULTS: U937 monocytic cells and
      macrophages (obtained with 10 nM phorbol-myristate-acetate) were exposed to Tyr,
      OH-Tyr or SQ at 0, 10, 75 and 200 MUM with/without native or oxidised LDL(oxLDL).
      Flow cytometry was used to achieve the expression of CD36 in both cell types
      exposed to oxLDL plus antioxidants, as well as the inhibition of
      monocyte/macrophage differentiation after oxLDL and apoptosis. SQ caused a dose
      dependent reduction of CD36 in the presence of native and moderate LDL in
      monocytes and macrophages. Phenotype-dependent cytotoxic and antiproliferative
      effects were found for OH-Tyr (p < 0.05), while SQ affected neither monocytes nor
      macrophages (p < 0.01). CONCLUSION: SQ does not prevent monocyte migration and
      activation into macrophages, but it would inhibit oxLDL uptake by macrophages, by
      reducing CD36 expression. This study provides new data about the role of the
      components of OO in the prevention of atherosclerosis.

PMID- 22648621
TI  - Leucine induces myofibrillar protein accretion in cultured skeletal muscle
      through mTOR dependent and -independent control of myosin heavy chain mRNA
      levels.
AB  - SCOPE: Nutritional intervention during muscle wasting aims to attenuate net
      muscle protein loss. Branched chain amino acids, especially leucine, are able to
      stimulate the anabolic mammalian target of rapamycin (mTOR) signalling cascade
      and protein synthesis. It has been suggested that muscle myofibrillar protein
      expression is more responsive to amino acid supplementation compared to
      cytoplasmic proteins, although accretion of myofibrillar proteins has not
      extensively been investigated. We hypothesized that leucine specifically
      increases myofibrillar protein synthesis in skeletal muscle. METHODS AND RESULTS:
      This hypothesis was investigated in C2C12 skeletal muscle cells using
      physiologically relevant culture conditions. Leucine supplementation specifically
      increased myofibrillar protein accretion, including myosin heavy chain-slow and 
      fast and myosin light chain 1 and -3 in C2C12 cells. Neither total protein
      content, nor de novo protein synthesis was affected, despite leucine-induced
      increased 4E-BP1 and S6K1 phosphorylation. Leucine supplementation did not affect
      myogenesis, measured by creatine kinase activity and myoblast fusion, either.
      Remarkably, leucine-induced increased myofibrillar protein accretion was
      accompanied by elevated MyHC mRNA levels, which involved mTOR-dependent and 
      independent regulation of MyHC-4 and MyHC-7 gene-expression, respectively.
      CONCLUSION: This study clearly demonstrates myofibrillar and not generic protein
      accretion in skeletal muscle following leucine supplementation, and suggests this
      involves pre-translational control of MyHC expression by leucine.

PMID- 22648622
TI  - Calcium-sensing receptor mediates dietary peptide-induced CCK secretion in
      enteroendocrine STC-1 cells.
AB  - SCOPE: Dietary peptides are potent stimulators of cholecystokinin (CCK)
      secretion, but the sensing mechanism in CCK-producing cells is poorly understood.
      Recently, it has been demonstrated that the calcium-sensing receptor (CaSR)
      mediates CCK secretion induced by amino acids. We investigated the role of CaSR
      in CCK secretions induced by various protein hydrolysates (egg albumin, meat,
      casein, azuki bean, soybean beta-conglycinin, and potato) in the enteroendocrine
      cell line STC-1. METHODS AND RESULTS: CCK secretions in response to these
      hydrolysates were measured in the STC-1 cells with or without CaSR antagonist
      (NPS 2143) treatment. Changes in intracellular calcium concentration ([Ca2+](i) )
      in response to protein hydrolysates were measured in Human embryonic kidney (HEK)
      293 cells transfected with CaSR-expression vector. Protein hydrolysates-induced
      CCK secretions were decreased by CaSR antagonist treatment, except meat
      hydrolysate-induced secretion. Protein hydrolysates increased [Ca2+](i) in CaSR
      transfected HEK 293 cells. CaSR antagonist treatment suppressed low molecular
      weight fractions of azuki hydrolysate-induced CCK secretion, but the secretion
      induced by both low and high molecular weight fractions of beta-conglycinin
      hydrolysate. Further, CCK secretion induced by peptide fractions (> 500 Da)
      derived from various protein hydrolysates were also reduced by CaSR antagonist.
      CONCLUSION: These results demonstrate that CaSR plays a significant role in
      sensing various dietary peptides in triggering CCK secretion in enteroendocrine
      cells.

PMID- 22648623
TI  - 2'-Hydroxyflavanone induces apoptosis through Egr-1 involving expression of Bax,
      p21, and NAG-1 in colon cancer cells.
AB  - SCOPE: Natural flavanones exhibit cancer preventive and/or therapeutic effects.
      The objective of this study was to investigate the molecular mechanism underlying
      the action of the antitumor activity of hydroxyflavanone using the HCT116 colon
      cancer cell line. METHODS AND RESULTS: We investigated the effect of
      hydroxyflavanones on antitumor activity. We found that 2'-hydroxyflavanone (2'
      HF) potently inhibited the clonogenicity of HCT116 cells. 2'-HF triggered
      apoptosis in both wild-type and p53-null HCT116 cells, as revealed by DNA
      fragmentation and caspase activation. 2'-HF upregulated nonsteroidal anti
      inflammatory drug-activated gene 1 (NAG-1) expression through induction of Egr-1.
      Silencing of NAG-1 or Egr-1 using small interfering RNA (siRNA) could attenuate
      2'-HF-induced apoptosis. Egr-1 also upregulated the proapoptotic gene Bax and the
      cell cycle inhibitor p21. CONCLUSION: Dietary 2'-HF may possess antitumor
      activity against human colon cancer.

PMID- 22648625
TI  - Ellagitannin metabolites, urolithin A glucuronide and its aglycone urolithin A,
      ameliorate TNF-alpha-induced inflammation and associated molecular markers in
      human aortic endothelial cells.
AB  - SCOPE: Numerous in vitro and in vivo studies indicate that ellagitannins exhibit
      anti-inflammatory, anti-atherosclerotic and anti-angiogenic activity which
      support their potential preventive effect against cardiovascular diseases.
      Ellagitannins exhibit low bioavailability and are transformed in the gut to
      ellagic acid and its microbiota metabolites urolithin A (Uro-A) and urolithin B
      (Uro-B). Urolithins are found in plasma mostly as glucuronides at low MUM
      concentrations. We investigated whether urolithin glucuronides and their
      aglycones exhibit vascular protective effects. METHODS AND RESULTS: Human aortic
      endothelial cells were exposed to tumor necrosis factor alpha and to Uro-A
      glucuronide, Uro-B glucuronide or their corresponding aglycones at low MUM
      concentrations to determine their effects on monocytes adhesion and endothelial
      cell migration. The levels of related adhesion cytokines and growth molecular
      markers were also measured. Uro-A glucuronide (~5-15 MUM) inhibited monocyte
      adhesion and endothelial cell migration in a significant manner. These effects
      were associated with a moderate but significant down-regulation of the levels of
      chemokine (C-C motif) ligand 2 (CCL2) and plasminogen activator inhibitor-1 (PAI
      1). Uro-A inhibited endothelial cell migration and was able to decrease the
      expression of CCL2 and interleukin-8 (IL-8). CONCLUSION: Our results suggest that
      these metabolites might be involved, at least in part, in the beneficial effects
      against cardiovascular diseases attributed to the consumption of ellagitannin
      containing foods.

PMID- 22648624
TI  - Dietary intake of rosmarinic acid by Apc(Min)  mice, a model of colorectal
      carcinogenesis: levels of parent agent in the target tissue and effect on adenoma
      development.
AB  - SCOPE: Rosmarinic acid (RA), a constituent of culinary herbs is considered to
      possess cancer chemopreventive properties. It has been shown to inhibit the
      development of cancer in preclinical models but data are conflicting and whether
      it can protect against gastrointestinal malignancies in vivo has not been
      examined. This study aimed to investigate the effect of RA on the development of
      intestinal adenomas in the Apc(Min) mouse model of colorectal carcinogenesis, and
      to correlate efficacy with levels of RA achieved in the plasma and
      gastrointestinal tract. METHODS AND RESULTS: RA inhibited the growth of APC10.1
      cells derived from Apc(Min) mouse adenomas, with an IC50 of 43 MUM. Consumption
      of dietary RA (0.3%) by Apc(Min) mice for 8 weeks post weaning decreased adenoma
      burden by ~35%, but the difference from controls was not significant. Although RA
      significantly decreased the frequency of large adenomas, the number of small ones
      increased. Using a novel validated HPLC assay, average levels of RA in the plasma
      and intestinal mucosa of these mice were found to be 1.1 MUM and 38 nmol/g,
      respectively. CONCLUSION: Chronic consumption of RA furnished quantifiable levels
      of parent compound in the plasma and intestinal tract of Apc(Min) mice and may
      slow adenoma development.

PMID- 22648626
TI  - Capsaicin induces CYP3A4 expression via pregnane X receptor and CCAAT/enhancer
      binding protein beta activation.
AB  - SCOPE: Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the principal pungent
      ingredient in hot red and chili peppers. Many studies have focused on the
      anticarcinogenic or chemopreventive activities of capsaicin. However, the
      influence of capsaicin on CYP3A4, its involvement in drug metabolism, and the
      underlying mechanisms remain unclear. METHODS AND RESULTS: Here, we examined the
      effect of capsaicin on CYP3A4 expression and the metabolism of CYP3A1 substrate,
      nifedipine in male Sprague-Dawley rats. Capsaicin induced the enzymatic activity
      and expression of CYP3A4 in HepG2 cells. Treatment with a human pregnane X
      receptor (hPXR) inhibitor reduced the inductive effects of capsaicin on CYP3A4
      expression. Capsaicin also induced the activation of CCAAT/enhancer-binding
      protein beta (C/EBPbeta). Moreover, capsaicin increased the activation of the
      transient receptor potential vanilloid type-1 receptor downstream signaling
      components Ca2+/calmodulin-dependent protein kinase and Akt. Capsaicin elevated
      the level of CYP3A1 in rat liver and significantly increased the
      biotransformation of nifedipine to dehydronifedipine. CONCLUSION: From these
      data, we conclude that capsaicin induces CYP3A4 expression in vitro and in vivo.
      This induction was achieved by the activation of hPXR and C/EBPbeta. Our results
      suggest that capsaicin might induce CYP3A4 expression; thus, exposure to
      capsaicin may increase the metabolism of CYP3A4 substrate and potentially cause
      food-drug interactions.

PMID- 22648627
TI  - Consumption of a grape extract supplement containing resveratrol decreases
      oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular
      disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial.
AB  - SCOPE: The cardioprotective role of resveratrol as part of the human diet is not
      yet clear. Our aim was to investigate the effect of a grape supplement containing
      8 mg resveratrol in oxidized LDL (LDLox), apolipoprotein-B (ApoB), and serum
      lipids on statin-treated patients in primary cardiovascular disease prevention
      (PCP). METHODS AND RESULTS: A triple-blind, randomized, placebo-controlled trial
      was conducted. Seventy-five patients (three parallel arms) consumed one capsule
      (350 mg) daily for 6 months containing resveratrol-enriched grape extract (GE
      RES, Stilvid(r)), grape extract (GE, similar polyphenolic content but no
      resveratrol), or placebo (maltodextrin). After 6 months, no changes were observed
      in the placebo group and only LDL cholesterol (LDLc) decreased by 2.9% (p =
      0.013) in the GE group. In contrast, LDLc (-4.5%, p = 0.04), ApoB (-9.8%, p =
      0.014), LDLox (-20%, p = 0.001), and LDLox/ApoB (-12.5%, p = 0.000) decreased in
      the Stilvid(r) group, whereas the ratio non-HDLc (total atherogenic cholesterol
      load)/ApoB increased (8.5%, p = 0.046). No changes were observed in hepatic,
      thyroid, and renal function. No adverse effects were observed in any of the
      patients. CONCLUSION: This GE-RES reduced atherogenic markers and might exert
      additional cardioprotection beyond the gold-standard medication in patients from
      PCP. The presence of resveratrol in the GE was necessary to achieve these
      effects.

PMID- 22648628
TI  - beta-Glucans are involved in immune-modulation of THP-1 macrophages.
AB  - SCOPE: We aimed to examine different immunological aspects of beta-glucans
      derived from different food sources (oat, barley and shiitake) on phorbol
      myristate acetate (PMA)-differentiated THP-1 macrophages. Commercially purified
      barley beta-glucan (commercial BG) and lentinan were included to compare beta
      glucans from the same origin but different degree of purity and processing.
      METHODS AND RESULTS: Chemical composition and molecular weight distribution of
      beta-glucan samples were determined. Inflammation-related gene expression
      kinetics (IL-1beta, IL-8, nuclear factor kappa B [NF-kappaB] and IL-10) after 3,
      6 and 24 h of stimulation with 100 MUg/mL beta-glucan were investigated. All
      tested beta-glucans mildly upregulated the observed inflammation-related genes
      with differential gene expression patterns. Similar gene expression kinetics, but
      different fold induction values, was found for the crude beta-glucan extracts and
      their corresponding commercial forms. Pre-incubation of THP-1 macrophages with
      beta-glucans prior to lipopolysaccharide (LPS) exposure decreased the induction
      of inflammation-related genes compared to LPS treatment. No production of nitric
      oxide (NO) and hydrogen peroxide (H2O2) was detected in beta-glucan stimulated
      THP-1 macrophages. Phagocytic activity was not different after stimulation by
      beta-glucan samples. CONCLUSION: Based on these in vitro analyses, it can be
      concluded that the analysed beta-glucans have varying levels of immunomodulating
      properties, which are likely related to structure, molecular weight and
      compositional characteristic of beta-glucan.

PMID- 22648629
TI  - Impact of dietary fibre-enriched ready-to-eat extruded snacks on the postprandial
      glycaemic response of non-diabetic patients.
AB  - Food intervention is a financially sensible way for prevention and treatment of
      diabetes. Extruded snack foods are considered high glycaemic products. Our
      previous research illustrated that postprandial glycaemic responses to snacks are
      manipulated by altering dietary fibre and starch contents. The current research
      assessed the effect of psyllium and oat bran on postprandial glycaemia and in
      vitro digestibility. Addition of psyllium fibre to extruded snack products
      significantly reduced both the in vitro and in vivo glycaemic responses of
      products compared to a control snack product recipe. Oat bran inclusion reduced
      in vitro starch digestibility but not in vivo glycaemic response. The inclusion
      of oat bran into the snack products appeared to extend the glycaemic response of
      individuals compared to the control snack, suggesting a possibility of prolonging
      glucose release and potentially affecting satiety responses. The positive effect
      in attenuating glucose response means that psyllium fibre could be a target for
      inclusion by the snack food industry to effectively manipulate postprandial
      glucose response of individuals.

PMID- 22648632
TI  - Synthesis of conformationally constrained benzoylureas as BH3-mimetics.
AB  - The design of small molecules that mimic the BH3 domain and bind to Bcl-2
      proteins has emerged as a promising approach to discovering novel anti-cancer
      therapeutics. We reveal the design and synthesis of conformationally constrained
      benzoylurea scaffolds as conformational probes. Central to helix mimicry, the
      intramolecular hydrogen bond in the benzoylurea plays a key role in the pre
      organisation of the acyclic substrates for cyclisation via ring closing
      metathesis, providing efficient access to the constrained mimetics.

PMID- 22648633
TI  - High resolution navigated three-dimensional T1-weighted hepatobiliary MRI using
      gadoxetic acid optimized for 1.5 Tesla.
AB  - PURPOSE: To determine optimal delay times and flip angles for T1-weighted
      hepatobiliary imaging at 1.5 Tesla (T) with gadoxetic acid and to demonstrate the
      feasibility of using a high-resolution navigated optimized T1-weighted pulse
      sequence to evaluate biliary disease. MATERIALS AND METHODS: Eight healthy
      volunteers were scanned at 1.5T using a T1-weighted three-dimensional (3D)-SPGR
      pulse sequence following the administration of 0.05 mmol/kg of gadoxetic acid.
      Navigator-gating enabled acquisition of high spatial resolution (1.2 * 1.4 * 1.8
      mm(3) , interpolated to 0.7 * 0.7 * 0.9 mm(3) ) images in approximately 5 min of
      free-breathing. Multiple breath-held acquisitions were performed at flip angles
      between 15 degrees  and 45 degrees  to optimize T1 weighting. To evaluate the
      performance of this optimized sequence in the setting of biliary disease, the
      image quality and biliary excretion of 51 consecutive clinical scans performed to
      assess primary sclerosing cholangitis (PSC) were evaluated. RESULTS: Optimal
      hepatobiliary imaging occurs at 15-25 min, using a 40 degrees  flip angle. The
      image quality and visualization of biliary excretion in the PSC scans were
      excellent, despite the decreased liver function in some patients. Visualization
      of reduced excretion often provided diagnostic information that was unavailable
      by conventional magnetic resonance cholangiopancreatography (MRCP). CONCLUSION:
      High-resolution navigated 3D-SPGR hepatobiliary imaging using gadoxetic acid and
      optimized scan parameters is technically feasible and can be clinically useful,
      even in patients with decreased hepatobiliary function.

PMID- 22648634
TI  - Identification of (L)-3-hydroxykynurenine O-sulfate in the buccal gland secretion
      of the parasitic lamprey, Lethenteron japonicum.
AB  - Parasitic lampreys are known to secrete proteins having anticoagulant and
      vasodilator activities from the buccal glands during feeding on their host's
      blood. However, small molecules in the secretion have never been explored in
      detail. We examined the secretion of Japanese liver lamprey (Lethenteron
      japonicum) for small molecules and found an intensely fluorescent substance upon
      gel filtration. After purification by anion-exchange chromatography and reversed
      phase HPLC, structure of the compound was determined to be L-3-hydroxykynurenine
      O-sulfate by NMR- and UV-spectrometry, complemented with enzymatic and chemical
      degradation. In vertebrates, the sulfate ester of 3-hydroxykynurenine is a
      compound that has been regarded as a urinary metabolite of tryptophan but not
      reported from normal tissues to date. Although the function of this molecule in
      the buccal glands remains to be elucidated, it is remarkable that the same
      substance was described in 1960s from two species of blood-sucking insects,
      Rhodnius prolixus and Triatoma infestans, suggesting its potential role in blood
      feeding.

PMID- 22648635
TI  - Mobile technologies among people with serious mental illness: opportunities for
      future services.
AB  - Several national bodies have proposed using mobile technology to improve mental
      health services. But rates of current use and interest in using technology to
      enhance services among individuals with serious mental illness are uncertain. The
      authors surveyed 1,592 individuals with serious mental illness regarding their
      use of mobile devices and interest in using mobile technologies to enhance mental
      health services. Seventy-two percent of survey respondents reported currently
      owning a mobile device, a rate approximately 12 % lower than the general adult
      population. The most common uses were for talking, followed by texting, and
      internet activities. Both mobile device users and nonusers expressed interest in
      future mobile services.

PMID- 22648637
TI  - Intra-operative fluorescent cholangiography using indocyanin green during robotic
      single site cholecystectomy.
AB  - BACKGROUND AND STUDY AIMS: Very recently, robotic single site cholecystectomy
      (RSSC) has been reported feasible and safe for selected cases. While an intra
      operative cholangiography can be performed, data is scarce with respect to its
      use. Indocyanin green (ICG) has been shown to be a viable option to visualize
      biliary anatomy. Since the introduction of a new near infrared camera integrated
      to the da Vinci Si System (Intuitive Surgical, Sunnyvale, CA), the surgeon is
      able to assess the biliary anatomy by a non-invasive and non-ionizing method.
      This paper presents the first report of ICG imaging during a RSSC. PATIENTS AND
      METHODS: Twelve consecutive patients presenting symptomatic cholelithiasis were
      prospectively enrolled. They underwent RSSC approximately 45 minutes after
      intravenous administration of ICG (2.5 mg). The biliary anatomy was analyzed
      using a near infrared camera integrated to the robot before and after the robotic
      dissection. RESULTS: Eight women and four men underwent the procedure. There was
      a port addition in one case and no peri-operative complications. Mean operative
      time was 85 minutes (range: 57-125). The cystic, common bile and common hepatic
      ducts were recognized by fluorescence imaging before the dissection in 91.7%,
      50%, and 33.3% of patients, respectively. At least one structure was visualized
      in 100% of patients. After the completion of Calot's triangle dissection, the
      cystic, common bile, and common hepatic ducts were recognized in 100%, 83.3%, and
      66.7% of cases respectively. CONCLUSIONS: RSSC using ICG for biliary tree
      fluorescence imaging can be performed safely. Fluorescent cholangiography enabled
      real-time identification of the extra-hepatic biliary anatomy using a near
      infrared camera integrated to the robot. Its routine clinical use merits further
      investigations.

PMID- 22648638
TI  - Simulation-based training and learning curves in laparoscopic Roux-en-Y gastric
      bypass (Br J Surg 2012; 99: 887-895).

PMID- 22648639
TI  - Critical appraisal of the 'wait and see' approach in rectal cancer for clinical
      complete responders after chemoradiation (Br J Surg 2012; 99: 897-909).

PMID- 22648640
TI  - Systematic review of haemorrhage and rupture of hepatocellular adenomas (Br J
      Surg 2012; 99: 911-916).

PMID- 22648641
TI  - Randomized clinical trial of glutamine-supplemented versus standard parenteral
      nutrition in infants with surgical gastrointestinal disease (Br J Surg 2012; 99:
      929-938).

PMID- 22648642
TI  - Selective hepatic vascular exclusion versus Pringle manoeuvre in liver resection
      for tumours encroaching on major hepatic veins (Br J Surg 2012; 99: 973-977).

PMID- 22648643
TI  - The surgical significance of residual mucosal abnormalities in rectal cancer
      following neoadjuvant chemoradiotherapy (Br J Surg 2012; 99: 993-1001).

PMID- 22648644
TI  - Pancolonic motor response to subsensory and suprasensory sacral nerve stimulation
      in patients with slow-transit constipation (Br J Surg 2012; 99: 1002-1010).

PMID- 22648645
TI  - Body composition and outcome in patients undergoing resection of colorectal liver
      metastases (Br J Surg 2012; 99: 550-557).

PMID- 22648647
TI  - Associated injuries in casualties with traumatic lower extremity amputations
      caused by improvised explosive devices (Br J Surg 2012; 99: 362-366).

PMID- 22648648
TI  - Randomized clinical trial of bilateral subtotal thyroidectomy versus total
      thyroidectomy for Graves' disease with a 5-year follow-up (Br J Surg 2012; 99:
      515-522).

PMID- 22648652
TI  - Use of electrowetting to measure dynamic interfacial tensions of a microdrop.
AB  - The adsorption of surface active species to liquid-liquid and to solid-liquid
      interfaces can have dramatic effects in microfluidics. In this paper we show how
      electrowetting on dielectric can be used to monitor a dynamic liquid-liquid
      interfacial tension (IFT) with a time resolution of O(1 s) using amplitude
      modulation of the AC voltage. This straightforward method, which requires less
      than a microlitre of sample, is demonstrated for aqueous drops containing Triton
      X-100 surfactant on a Teflon AF-coated substrate and with heptane as the
      immiscible oil ambient. Under these conditions, next to extracting the oil-water
      IFT (gamma(ow)), also the effective water-substrate IFT difference
      (Deltagamma(ws)) can be obtained from the oil-water IFT and the Young's angle.
      Both gamma(ow) and gamma(ws) decrease over time due to adsorption. The measured
      dynamic oil-water IFT compares well to results of pendant drop experiments.

PMID- 22648653
TI  - The risk of all-cause mortality is inversely related to serum 25(OH)D levels.
AB  - CONTEXT AND OBJECTIVES: Vitamin D plays a key role in maintaining bone health,
      but evidence for its nonskeletal effects is inconsistent. This study aims to
      examine the association between serum 25-hydroxyvitamin D [25(OH)D] levels and
      all-cause mortality in a large general population cohort. DESIGN, PARTICIPANTS,
      AND SETTING: Using the computerized database of the largest health care provider
      in Israel, we identified a cohort of subjects 20 years old or older with serum
      25(OH)D levels measured between January 2008 and December 2009. Vital status was
      ascertained through August 2011. RESULTS: Median follow-up was 28.5 months
      (interquartile range 23.8-33.5 months); 7,247 of 182,152 participants (4.0%)
      died. Subjects who died had significantly lower serum 25(OH)D levels (mean 44.8
      +/- 24.2 nmol/liter) than those alive at the end of follow-up (51.0 +/- 23.2
      nmol/liter), P < 0.001. After adjustment for age, gender, ethnicity, and
      seasonality, the hazard ratio (HR) for all-cause mortality was 2.02 [95%
      confidence interval (CI) 1.89-2.15] for the lowest serum 25(OH)D quartile (<33.8
      nmol/liter) compared with the highest. After further adjustment for comorbidity,
      use of vitamin D supplements and statins, smoking, socioeconomic status, and body
      mass index, the HR was 1.81 (95% CI 1.69-1.95). This remained, even after
      adjustment for serum low-density lipoprotein, high-density lipoprotein, calcium
      level (corrected for serum albumin levels), and glomerular filtration rate, 1.85
      (95% CI 1.70-2.01). The fully adjusted HR associated with being in the second
      25(OH)D quartile (33.8-49.4 nmol/liter) was 1.25 (95% CI 1.16-1.34). CONCLUSIONS:
      All-cause mortality is independently and inversely associated with serum 25(OH)D
      levels at levels less than 50 nmol/liter.

PMID- 22648654
TI  - Hypoxia-induced microRNA-20a expression increases ERK phosphorylation and
      angiogenic gene expression in endometriotic stromal cells.
AB  - CONTEXT: Aberrant activation of MAPK has been implicated to play important roles
      in pathological processes of endometriosis. However, how MAPK are constitutively
      activated in endometriotic tissues remains largely unknown. microRNA are small
      noncoding RNA that regulate the stability or translational efficiency of target
      mRNA by interacting with the 3' untranslated region. Thus, miRNA are thought to
      be modulators of the transcriptional response, fine-tuning gene expression.
      OBJECTIVE: The aim of this study was to evaluate the functional roles of microRNA
      20a (miR20a) in MAPK activation and the pathogenesis of endometriosis. DESIGN:
      miR20a expression was analyzed in nonpaired (endometrium = 17; endometriosis =
      37) and paired (n = 12) endometriotic tissues by quantitative RT-PCR.
      Overexpression of miR20a in eutopic endometrial stromal cells or inhibition of
      miR20a in ectopic endometriotic stromal cells was used to evaluate its impact on
      ERK phosphorylation and subsequently angiogenesis- and proliferation-related gene
      expression. RESULTS: Levels of miR20a were up-regulated in endometriotic stromal
      cells. Elevation of miR20a was up-regulated by hypoxia inducible factor-1alpha.
      The up-regulation of miR20a causes the down-regulation of dual-specificity
      phosphatase-2, which leads to prolonged ERK phosphorylation and an increase in
      the expression of several angiogenic genes. Furthermore, the up-regulation of
      miR20a enhances the prostaglandin E(2)-induced expression of fibroblast growth
      factor-9, a potent mitogen that stimulates both endothelial and endometrial cell
      proliferation. CONCLUSION: Our findings provide the novel mechanism that not only
      functionally links together hypoxic stress, miR20a expression, aberrant ERK
      phosphorylation, and angiogenesis but also demonstrates that miR20a is an
      important modulator in the development of endometriosis.

PMID- 22648655
TI  - Bar graphs depicting averages are perceptually misinterpreted: the within-the-bar
      bias.
AB  - Perhaps the most common method of depicting data, in both scientific
      communication and popular media, is the bar graph. Bar graphs often depict
      measures of central tendency, but they do so asymmetrically: A mean, for example,
      is depicted not by a point, but by the edge of a bar that originates from a
      single axis. Here we show that this graphical asymmetry gives rise to a
      corresponding cognitive asymmetry. When viewers are shown a bar depicting a mean
      value and are then asked to judge the likelihood of a particular data point being
      part of its underlying distribution, viewers judge points that fall within the
      bar as being more likely than points equidistant from the mean, but outside the
      bar--as if the bar somehow "contained" the relevant data. This "within-the-bar
      bias" occurred (a) for graphs with and without error bars, (b) for bars that
      originated from both lower and upper axes, (c) for test points with equally
      extreme numeric labels, (d) both from memory (when the bar was no longer visible)
      and in online perception (while the bar was visible during the judgment), (e)
      both within and between subjects, and (f) in populations including college
      students, adults from the broader community, and online samples. We posit that
      this bias may arise due to principles of object perception, and we show how it
      has downstream implications for decision making.

PMID- 22648656
TI  - Auditory hindsight bias.
AB  - People who know the outcome of an event tend to overestimate their own prior
      knowledge or others' naive knowledge of it. This hindsight bias pervades
      cognition, lending the world an unwarranted air of inevitability. In four
      experiments, we showed how knowing the identities of words causes people to
      overestimate others' naive ability to identify moderately to highly degraded
      spoken versions of those words. We also showed that this auditory hindsight bias
      occurs despite people's efforts to avoid it. We discuss our findings in the
      context of communication, in which speakers overestimate the clarity of their
      message and listeners overestimate their understanding of the message.

PMID- 22648657
TI  - The impact of asthma health education for parents of children attending head
      start centers.
AB  - Parents of children who attend Head Start Centers are key participants in the
      health promotion and care of their own children. This non-randomized,
      longitudinal study aimed to test the effectiveness of an educational intervention
      based on the asthma and healthy homes curriculum targeting parents of Head Start
      children with or without an asthma diagnosis. One hundred and fifteen parents of
      children in Head Start Centers received an educational intervention at their
      corresponding sites, additionally pre- and post-test surveys were administered to
      measure educational intervention outcomes. A follow-up survey was conducted 6
      months after the educational intervention was offered. Results showed a
      statistically significant increase in asthma and healthy home-knowledge (p <
      0.001) in several areas. At 6 months post-intervention (54.4 %) (61 participants)
      were contacted and 98.4 % of made changes in their households as a result of
      their training. This study suggests that education can improve knowledge and
      change behaviors for the well-being of the residents of that household.

PMID- 22648658
TI  - Clonal re-introduction of endangered plant species: the case of German False
      Tamarisk in pre-alpine rivers.
AB  - The scope of re-introduction as a measure for plant species protection is
      increasing, but as long as no standardized methods are available, species
      specific assessments are necessary to determine whether seeds, adult plants or
      plant fragments should be used. The endangered German False Tamarisk (Myricaria
      germanica), which occurs on gravel bars along pre-alpine rivers, is difficult to
      grow from seeds. Thus, propagation of stem cuttings was investigated as an
      alternative method. Experiments were conducted in a greenhouse and a field site
      with three treatments: cutting length 5 or 10 cm, vertical burial 5 or 10 cm, and
      water level low or high. Plants grown in the greenhouse were transplanted to the
      River Isar to test establishment of rooted cuttings on gravel bars. The cuttings
      in the greenhouse showed high survival (34-96 %). Survival and biomass production
      were greatest for 10-cm cuttings buried at 10-cm depth, while only one of the 5
      cm cuttings survived at this depth, and no significant effect of variation in
      water level was observed. None of the cuttings transplanted to field sites
      survived, most likely because of drought stress and competition. We conclude that
      for re-introduction of Myricaria germanica rooted cuttings can be easily produced
      in large quantities, while transplantation to near-natural environments has to be
      improved to reduce mortality.

PMID- 22648659
TI  - Molecular characterization, expression patterns, and ligand-binding properties of
      two odorant-binding protein genes from Orthaga achatina (Butler) (Lepidoptera:
      Pyralidae).
AB  - It is postulated that insect pheromone-binding proteins (PBPs) are involved in
      sex pheromone reception, while the general odorant-binding proteins (GOBPs) are
      involved in reception of the general odorants including plant volatiles. However,
      this functional specificity is not completely conclusive. In the present study,
      full-length sequences of two new OBP genes were molecularly identified as
      OachPBP1 and OachGOBP2 from Orthaga achatina, an important pest of the camphor
      tree Cinnamomum camphora. Quantification of transcript levels by qRT-PCR showed
      that the two genes highly expressed in antennae, with OachPBP1 male-biased and
      OachGOBP2 similar between sexes. These expression patterns are consistent with
      the generally proposed functions of PBPs and GOBPs. With the recombinant proteins
      obtained by a bacterial expression system, the binding specificity of these
      proteins was further investigated and compared using the competitive binding
      assay. OachPBP1 exhibited high binding affinities with all three putative sex
      pheromones and 10 pheromone analogs, supporting its role in pheromone reception.
      On the other hand, in addition to binding with some plant volatiles, OachGOBP2
      surprisingly displayed similar or even higher binding affinities with the sex
      pheromones than OachPBP1. Therefore, we propose that OachGOBP2 might play roles
      in reception of sex pheromone. Additionally, plant volatiles farnesol and
      farnesene showed high binding with both OachGOBP2 and OachPBP1, suggesting that
      these volatile chemicals have regulatory functions in the behavior of O.
      achatina.

PMID- 22648660
TI  - Using a Delphi process to develop an effective train-the-trainers program to
      train health and social care professionals throughout Europe.
AB  - Research has shown that developing a Train-the-Trainers (TTT) program is
      important if agencies are to implement guidelines, but the most effective way to
      deliver a TTT program remains unanswered. This article presents data from a 3
      round Internet-based Delphi process, which was used to help develop consensus
      based guidelines for a TTT programme to deliver to health and social care
      professionals throughout Europe a curriculum on traumatic stress. In Round 1, 74
      experts rated the importance of statements relating to the TTT field and then
      reassessed their scores in the light of others' responses in subsequent rounds.
      Forty-one (67%) of 61 statements achieved consensus (defined as having a mean
      score >7 or < 3 on the 0-9 rating scales used and 70% of participants scoring 7
      and above or 3 and below) for inclusion. Key TTT components included interactive
      and practical presentations, delivery to groups of 7-12 people over 2 days,
      external and local expert facilitation, course manuals, refresher courses, and
      supervision. The Delphi process allowed a consensus to be achieved in an area in
      which there are limitations in the current evidence.

PMID- 22648663
TI  - Fulminant Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare, severe, and often fatal
      disorder. Its hereditary and sporadic form can present as a significant
      diagnostic challenge to the otolaryngologist. This report describes two fatal
      cases of adult patients with HLH initially presented as infectious mononucleosis
      to an otorhinolaryngologist. The clinical presentation, serological and
      histological features, and management are discussed.

PMID- 22648661
TI  - Sitagliptin reduces plaque macrophage content and stabilises arteriosclerotic
      lesions in Apoe (-/-) mice.
AB  - AIMS/HYPOTHESIS: Inhibitors of dipeptidyl peptidase-IV (DPP-IV), such as
      sitagliptin, increase glucagon-like peptide-1 (GLP-1) concentrations and are
      current treatment options for patients with type 2 diabetes mellitus. As patients
      with diabetes exhibit a high risk of developing severe atherosclerosis, we
      investigated the effect of sitagliptin on atherogenesis in Apoe (-/-) mice.
      METHODS: Apoe (-/-) mice were fed a high-fat diet and treated with either
      sitagliptin or placebo for 12 weeks. Plaque size and plaque composition were
      analysed using Oil Red O staining and immunohistochemistry. Furthermore, in vitro
      experiments with the modified Boyden chamber and with gelatine zymography were
      performed to analyse the effects of GLP-1 on isolated human monocyte migration
      and metalloproteinase-9 (MMP-9) release. RESULTS: Treatment of Apoe (-/-) mice
      with sitagliptin significantly reduced plaque macrophage infiltration (the aortic
      root and aortic arch both showing a 67% decrease; p < 0.05) and plaque MMP-9
      levels (aortic root showing a 69% and aortic arch a 58% reduction; both p < 0.01)
      compared with controls. Moreover, sitagliptin significantly increased plaque
      collagen content more than twofold (aortic root showing an increase of 58% and
      aortic arch an increase of 73%; both p < 0.05) compared with controls but did not
      change overall lesion size (8.1 +/- 3.5% vs 5.1 +/- 2.5% for sitagliptin vs
      controls; p=NS). In vitro, pretreatment of isolated human monocytes with GLP-1
      significantly decreased cell migration induced by both monocyte chemotactic
      protein-1 and by the protein known as regulated on activation, normal T cell
      expressed and secreted (RANTES) in a concentration-dependent manner. Furthermore,
      GLP-1 significantly decreased MMP-9 release from isolated human monocyte-derived
      macrophages. CONCLUSIONS/INTERPRETATION: Sitagliptin reduces plaque inflammation
      and increases plaque stability, potentially by GLP-1-mediated inhibition of
      chemokine-induced monocyte migration and macrophage MMP-9 release. The effects
      observed may provide potential mechanisms for how DPP-IV inhibitors could
      modulate vascular disease in high-risk patients with type 2 diabetes mellitus.

PMID- 22648664
TI  - Women who know their place : sex-based differences in spatial abilities and their
      evolutionary significance.
AB  - Differences between men and women in the performance of tests designed to measure
      spatial abilities are explained by evolutionary psychologists in terms of
      adaptive design. The Hunter-Gatherer Theory of Spatial Ability suggests that the
      adoption of a hunter-gatherer lifestyle (assuming a sexual division of labor)
      created differential selective pressure on the development of spatial skills in
      men and women and, therefore, cognitive differences between the sexes. Here, we
      examine a basic spatial skill-wayfinding (the ability to plan routes and navigate
      a landscape)-in men and women in a natural, real-world setting as a means of
      testing the proposition that sex-based differences in spatial ability exist
      outside of the laboratory. Our results indicate that when physical differences
      are accounted for, men and women with equivalent experience perform equally well
      at complex navigation tasks in a real-world setting. We conclude that experience,
      gendered patterns of activity, and self-assessment are contributing factors in
      producing previously reported differences in spatial ability.

PMID- 22648662
TI  - Type 2 diabetes mellitus is associated with an imbalance in circulating
      endothelial and smooth muscle progenitor cell numbers.
AB  - AIMS/HYPOTHESIS: Individuals with type 2 diabetes mellitus have increased rates
      of macrovascular disease (MVD). Endothelial progenitor cells (EPCs), circulating
      angiogenic cells (CACs) and smooth muscle progenitor cells (SMPCs) are suggested
      to play a role in the pathogenesis of MVD. The relationship between
      vasoregenerative EPCs or CACs and damaging SMPCs and the development of
      accelerated MVD in diabetes is still unknown. We tried to elucidate whether EPC,
      CAC and SMPC numbers and differentiation capacities in vitro differ in patients
      with and without diabetes or MVD. METHODS: Peripheral blood was obtained from
      individuals with and without diabetes and MVD (coronary or peripheral artery
      disease). EPC and SMPC numbers were determined with flow cytometry. Furthermore,
      CAC and SMPC numbers were quantified after in vitro culture. Their in vitro
      differentiation capacity was investigated with real-time RT-PCR and quantitative
      immunofluorescence. RESULTS: In diabetic patients both EPC and CAC levels were
      reduced (1.3-fold [p < 0.05] and 1.5-fold [p < 0.05], respectively). CAC
      outgrowth from diabetic patients with MVD was reduced 1.5-fold compared with
      diabetic patients without MVD (p < 0.05). SMPC levels were similar between
      diabetic patients and healthy controls. The CAC/SMPC ratio of in vitro cultured
      progenitor cells was reduced 2.3-fold in samples from diabetic patients (p <
      0.001). The differentiation capacity of CACs and SMPCs in vitro remained similar
      independently of diabetes or MVD. CONCLUSIONS/INTERPRETATION: The ratio between
      EPCs or CACs and SMPCs is disturbed in type 2 diabetes in favour of SMPCs. This
      may translate into reduced vascular repair capacity, thereby promoting MVD in
      type 2 diabetes.

PMID- 22648665
TI  - Screening of Venezuelan medicinal plant extracts for cytostatic and cytotoxic
      activity against tumor cell lines.
AB  - There are estimated to be more than 20,000 species of plants in Venezuela, of
      which more than 1500 are used for medicinal purposes by indigenous and local
      communities. Only a relatively small proportion of these have been evaluated in
      terms of their potential as antitumor agents. In this study, we screened 308
      extracts from 102 species for cytostatic and cytotoxic activity against a panel
      of six tumor cell lines using a 24-h sulphorhodamine B assay. Extracts from
      Clavija lancifolia, Hamelia patens, Piper san-vicentense, Physalis cordata,
      Jacaranda copaia, Heliotropium indicum, and Annona squamosa were the most
      cytotoxic, whereas other extracts from Calotropis gigantea, Hyptis dilatata,
      Chromolaena odorata, Siparuna guianensis, Jacaranda obtusifolia, Tapirira
      guianensis, Xylopia aromatica, Protium heptaphyllum, and Piper arboreum showed
      the greatest cytostatic activity. These results confirm previous reports on the
      cytotoxic activities of the above-mentioned plants as well as prompting further
      studies on others such as C. lancifolia and H. dilatata that have not been so
      extensively studied.

PMID- 22648667
TI  - Alperujo extract, hydroxytyrosol, and 3,4-dihydroxyphenylglycol are bioavailable
      and have antioxidant properties in vitamin E-deficient rats--a proteomics and
      network analysis approach.
AB  - SCOPE: Olive products are rich in phenolic compounds, which are natural
      antioxidants in vitro. We tested the in vivo effects of alperujo, an olive
      production by-product, as well as hydroxytyrosol and 3,4-dihydroxyphenylglycol
      (DHPG) isolated from alperujo, on indices and pathways of oxidative and metabolic
      stress in a vitamin E-deficient rat model. METHODS AND RESULTS: Rats were fed a
      vitamin E-deficient diet for 10 weeks, followed by this diet supplemented with
      either 100 mg/kg diet dalpha-tocopherol, alperujo extract, hydroxytyrosol, or 10
      mg/kg diet DHPG, for a further 2 weeks. We detected alperujo phenolics in tissues
      and blood, indicating they are bioavailable. Alperujo extract partially
      ameliorated elevated plasma levels of thiobarbituric acid reactive substances and
      also lowered plasma cholesterol levels, whereas hydroxytyrosol increased plasma
      triglyceride levels. Proteomics and subsequent network analysis revealed that
      hepatic mitochondrial aldehyde dehydrogenase (ALDH2), of which protein and
      activity levels were regulated by dalpha-tocopherol and olive phenolics,
      represents a novel central regulatory protein hub affected by the dietary
      interventions. CONCLUSION: The in vivo free radical scavenging properties of
      olive phenolics appear relatively modest in our model. But alternative
      mechanisms, including regulation of ALDH2, may represent relevant antioxidant
      mechanisms by which dietary olive phenolics could have beneficial impact on
      cardiovascular health.

PMID- 22648668
TI  - Methods guide for authors of systematic reviews of medical tests: a collaboration
      between the Agency for Healthcare Research and Quality (AHRQ) and the Journal of
      General Internal Medicine.

PMID- 22648669
TI  - Chapter 1: Introduction to the Methods Guide for Medical Test Reviews.
AB  - Evaluation of medical tests presents challenges distinct from those involved in
      the evaluation of therapies; in particular, the very great importance of context
      and the dearth of comprehensive RCTs aimed at comparing the clinical outcomes of
      different tests and test strategies. Available guidance provides some
      suggestions: 1) Use of the PICOTS typology for clarifying the context relevant to
      the review, and 2) use of an organizing framework for classifying the types of
      medical test evaluation studies and their relationship to potential key
      questions. However, there is a diversity of recommendations for reviewers of
      medical tests and a proliferation of concepts, terms, and methods. As a
      contribution to the field, this Methods Guide for Medical Test Reviews seeks to
      provide practical guidance for achieving the goals of clarity, consistency,
      tractability, and usefulness.

PMID- 22648670
TI  - Chapter 2: medical tests guidance (2) developing the topic and structuring
      systematic reviews of medical tests: utility of PICOTS, analytic frameworks,
      decision trees, and other frameworks.
AB  - Topic development and structuring a systematic review of diagnostic tests are
      complementary processes. The goals of a medical test review are to identify and
      synthesize evidence to evaluate the impacts alternative testing strategies on
      health outcomes and to promote informed decision making. A common challenge is
      that the request for a review may state the claim for the test ambiguously. Due
      to the indirect impact of medical tests on clinical outcomes, reviewers need to
      identify which intermediate outcomes link a medical test to improved clinical
      outcomes. In this paper, we propose the use of five principles to deal with
      challenges: the PICOTS typology (patient population, intervention, comparator,
      outcomes, timing, setting), analytic frameworks, simple decision trees, other
      organizing frameworks and rules for when diagnostic accuracy is sufficient.

PMID- 22648671
TI  - Chapter 3: choosing the important outcomes for a systematic review of a medical
      test.
AB  - In this chapter of the Evidence-based Practice Centers Methods Guide for Medical
      Tests, we describe how the decision to use a medical test generates a broad range
      of outcomes and that each of these outcomes should be considered for inclusion in
      a systematic review. Awareness of these varied outcomes affects how a decision
      maker balances the benefits and risks of the test; therefore, a systematic review
      should present the evidence on these diverse outcomes. The key outcome categories
      include clinical management outcomes and direct health effects; emotional,
      social, cognitive, and behavioral responses to testing; legal and ethical
      outcomes, and costs. We describe the challenges of incorporating these outcomes
      in a systematic review, suggest a framework for generating potential outcomes for
      inclusion, and describe the role of stakeholders in choosing the outcomes for
      study. Finally, we give examples of systematic reviews that either included a
      range of outcomes or that might have done so. The following are the key messages
      in this chapter: Consider both the outcomes that are relevant to the process of
      testing and those that are relevant to the results of the test. Consider
      inclusion of outcomes in all five domains: clinical management effects, direct
      test effects; emotional, social, cognitive and behavioral effects; legal and
      ethical effects, and costs. Consider to which group the outcomes of testing are
      most relevant. Given resource limitations, prioritize which outcomes to include.
      This decision depends on the needs of the stakeholder(s), who should be assisted
      in prioritizing the outcomes for inclusion.

PMID- 22648672
TI  - Chapter 4: effective search strategies for systematic reviews of medical tests.
AB  - This article discusses techniques that are appropriate when developing search
      strategies for systematic reviews of medical tests. This includes general advice
      for searching for systematic reviews and issues specific to systematic reviews of
      medical tests. Diagnostic search filters are currently not sufficiently developed
      for use when searching for systematic reviews. Instead, authors should construct
      a highly sensitive search strategy that uses both controlled vocabulary and text
      words. A comprehensive search should include multiple databases and sources of
      grey literature. A list of subject-specific databases is included in this
      article.

PMID- 22648673
TI  - Chapter 5: assessing risk of bias as a domain of quality in medical test studies.
AB  - Assessing methodological quality is a necessary activity for any systematic
      review, including those evaluating the evidence for studies of medical test
      performance. Judging the overall quality of an individual study involves
      examining the size of the study, the direction and degree of findings, the
      relevance of the study, and the risk of bias in the form of systematic error,
      internal validity, and other study limitations. In this chapter of the Methods
      Guide for Medical Test Reviews, we focus on the evaluation of risk of bias in the
      form of systematic error in an individual study as a distinctly important
      component of quality in studies of medical test performance, specifically in the
      context of estimating test performance (sensitivity and specificity). We make the
      following recommendations to systematic reviewers: 1) When assessing study
      limitations that are relevant to the test under evaluation, reviewers should
      select validated criteria that examine the risk of systematic error, 2)
      categorizing the risk of bias for individual studies as "low," "medium," or
      "high" is a useful way to proceed, and 3) methods for determining an overall
      categorization for the study limitations should be established a priori and
      documented clearly.

PMID- 22648674
TI  - Chapter 6: assessing applicability of medical test studies in systematic reviews.
AB  - Use of medical tests should be guided by research evidence about the accuracy and
      utility of those tests in clinical care settings. Systematic reviews of the
      literature about medical tests must address applicability to real-world decision
      making. Challenges for reviews include: (1) lack of clarity in key questions
      about the intended applicability of the review, (2) numerous studies in many
      populations and settings, (3) publications that provide too little information to
      assess applicability, (4) secular trends in prevalence and the spectrum of the
      condition for which the test is done, and (5) changes in the technology of the
      test itself. We describe principles for crafting reviews that meet these
      challenges and capture the key elements from the literature necessary to
      understand applicability.

PMID- 22648675
TI  - Chapter 7: grading a body of evidence on diagnostic tests.
AB  - INTRODUCTION: Grading the strength of a body of diagnostic test evidence involves
      challenges over and above those related to grading the evidence from health care
      intervention studies. This chapter identifies challenges and outlines principles
      for grading the body of evidence related to diagnostic test performance.
      CHALLENGES: Diagnostic test evidence is challenging to grade because standard
      tools for grading evidence were designed for questions about treatment rather
      than diagnostic testing; and the clinical usefulness of a diagnostic test depends
      on multiple links in a chain of evidence connecting the performance of a test to
      changes in clinical outcomes. PRINCIPLES: Reviewers grading the strength of a
      body of evidence on diagnostic tests should consider the principle domains of
      risk of bias, directness, consistency, and precision, as well as publication
      bias, dose response association, plausible unmeasured confounders that would
      decrease an effect, and strength of association, similar to what is done to grade
      evidence on treatment interventions. Given that most evidence regarding the
      clinical value of diagnostic tests is indirect, an analytic framework must be
      developed to clarify the key questions, and strength of evidence for each link in
      that framework should be graded separately. However if reviewers choose to
      combine domains into a single grade of evidence, they should explain their
      rationale for a particular summary grade and the relevant domains that were
      weighed in assigning the summary grade.

PMID- 22648677
TI  - Chapter 9: options for summarizing medical test performance in the absence of a
      "gold standard".
AB  - The classical paradigm for evaluating test performance compares the results of an
      index test with a reference test. When the reference test does not mirror the
      "truth" adequately well (e.g. is an "imperfect" reference standard), the typical
      ("naive") estimates of sensitivity and specificity are biased. One has at least
      four options when performing a systematic review of test performance when the
      reference standard is "imperfect": (a) to forgo the classical paradigm and assess
      the index test's ability to predict patient relevant outcomes instead of test
      accuracy (i.e., treat the index test as a predictive instrument); (b) to assess
      whether the results of the two tests (index and reference) agree or disagree
      (i.e., treat them as two alternative measurement methods); (c) to calculate
      "naive" estimates of the index test's sensitivity and specificity from each study
      included in the review and discuss in which direction they are biased; (d)
      mathematically adjust the "naive" estimates of sensitivity and specificity of the
      index test to account for the imperfect reference standard. We discuss these
      options and illustrate some of them through examples.

PMID- 22648676
TI  - Chapter 8: meta-analysis of test performance when there is a "gold standard".
AB  - Synthesizing information on test performance metrics such as sensitivity,
      specificity, predictive values and likelihood ratios is often an important part
      of a systematic review of a medical test. Because many metrics of test
      performance are of interest, the meta-analysis of medical tests is more complex
      than the meta-analysis of interventions or associations. Sometimes, a helpful way
      to summarize medical test studies is to provide a "summary point", a summary
      sensitivity and a summary specificity. Other times, when the sensitivity or
      specificity estimates vary widely or when the test threshold varies, it is more
      helpful to synthesize data using a "summary line" that describes how the average
      sensitivity changes with the average specificity. Choosing the most helpful
      summary is subjective, and in some cases both summaries provide meaningful and
      complementary information. Because sensitivity and specificity are not
      independent across studies, the meta-analysis of medical tests is fundamentaly a
      multivariate problem, and should be addressed with multivariate methods. More
      complex analyses are needed if studies report results at multiple thresholds for
      positive tests. At the same time, quantitative analyses are used to explore and
      explain any observed dissimilarity (heterogeneity) in the results of the examined
      studies. This can be performed in the context of proper (multivariate) meta
      regressions.

PMID- 22648678
TI  - Chapter 10: deciding whether to complement a systematic review of medical tests
      with decision modeling.
AB  - Limited by what is reported in the literature, most systematic reviews of medical
      tests focus on "test accuracy" (or better, test performance), rather than on the
      impact of testing on patient outcomes. The link between testing, test results and
      patient outcomes is typically complex: even when testing has high accuracy, there
      is no guarantee that physicians will act according to test results, that patients
      will follow their orders, or that the intervention will yield a beneficial
      endpoint. Therefore, test performance is typically not sufficient for assessing
      the usefulness of medical tests. Modeling (in the form of decision or economic
      analysis) is a natural framework for linking test performance data to clinical
      outcomes. We propose that (some) modeling should be considered to facilitate the
      interpretation of summary test performance measures by connecting testing and
      patient outcomes. We discuss a simple algorithm for helping systematic reviewers
      think through this possibility, and illustrate it by means of an example.

PMID- 22648679
TI  - Chapter 11: challenges in and principles for conducting systematic reviews of
      genetic tests used as predictive indicators.
AB  - In this paper, we discuss common challenges in and principles for conducting
      systematic reviews of genetic tests. The types of genetic tests discussed are
      those used to 1). determine risk or susceptibility in asymptomatic individuals;
      2). reveal prognostic information to guide clinical management in those with a
      condition; or 3). predict response to treatments or environmental factors. This
      paper is not intended to provide comprehensive guidance on evaluating all genetic
      tests. Rather, it focuses on issues that have been of particular concern to
      analysts and stakeholders and on areas that are of particular relevance for the
      evaluation of studies of genetic tests. The key points include: The general
      principles that apply in evaluating genetic tests are similar to those for other
      prognostic or predictive tests, but there are differences in how the principles
      need to be applied or the degree to which certain issues are relevant. A clear
      definition of the clinical scenario and an analytic framework is important when
      evaluating any test, including genetic tests. Organizing frameworks and analytic
      frameworks are useful constructs for approaching the evaluation of genetic tests.
      In constructing an analytic framework for evaluating a genetic test, analysts
      should consider preanalytic, analytic, and postanalytic factors; such factors are
      useful when assessing analytic validity. Predictive genetic tests are generally
      characterized by a delayed time between testing and clinically important events.
      Finding published information on the analytic validity of some genetic tests may
      be difficult. Web sites (FDA or diagnostic companies) and gray literature may be
      important sources. In situations where clinical factors associated with risk are
      well characterized, comparative effectiveness reviews should assess the added
      value of using genetic testing along with known factors compared with using the
      known factors alone. For genome-wide association studies, reviewers should
      determine whether the association has been validated in multiple studies to
      minimize both potential confounding and publication bias. In addition, reviewers
      should note whether appropriate adjustments for multiple comparisons were used.

PMID- 22648681
TI  - Partner report of paternal depression using the Edinburgh Postnatal Depression
      Scale-Partner.
AB  - Similar to maternal depression, paternal depression may have adverse effects on
      the family environment (e.g., partner mental health, child behavior). Detection
      of paternal depression is rare because the maternal-child health care system
      usually only screens for maternal depression. The scarcity of paternal depression
      screening and detection is due to fathers not usually being involved in the
      maternal-child health care system and, therefore, unavailable for depression
      screening. The purpose of this study was to assess the psychometric
      characteristics of the Edinburgh Postnatal Depression Scale-Partner Version (EPDS
      P) in detecting paternal depression through maternal report. The EPDS-P, rated by
      the mother, was found to be a reliable and valid measure of paternal depression
      when compared to other well-validated measures of depression. The EPDS-P has
      clinical utility in the maternal-child health care system by making it possible
      to screen for paternal depression without the father being present. Proxy
      screening for paternal depression can be beneficial for early detection and
      treatment of paternal depression both in the perinatal period and through a
      child's early life. Detection and treatment of paternal depression reduces the
      risk of long-term depression in fathers.

PMID- 22648680
TI  - Chapter 12: systematic review of prognostic tests.
AB  - A number of new biological markers are being studied as predictors of disease or
      adverse medical events among those who already have a disease. Systematic reviews
      of this growing literature can help determine whether the available evidence
      supports use of a new biomarker as a prognostic test that can more accurately
      place patients into different prognostic groups to improve treatment decisions
      and the accuracy of outcome predictions. Exemplary reviews of prognostic tests
      are not widely available, and the methods used to review diagnostic tests do not
      necessarily address the most important questions about prognostic tests that are
      used to predict the time-dependent likelihood of future patient outcomes. We
      provide suggestions for those interested in conducting systematic reviews of a
      prognostic test. The proposed use of the prognostic test should serve as the
      framework for a systematic review and to help define the key questions. The
      outcome probabilities or level of risk and other characteristics of prognostic
      groups are the most salient statistics for review and perhaps meta-analysis.
      Reclassification tables can help determine how a prognostic test affects the
      classification of patients into different prognostic groups, hence their
      treatment. Review of studies of the association between a potential prognostic
      test and patient outcomes would have little impact other than to determine
      whether further development as a prognostic test might be warranted.

PMID- 22648682
TI  - Detection of platypus-type L/D-peptide isomerase activity in aqueous extracts of
      papaya fruit.
AB  - Peptide isomerase catalyses the post-translational isomerisation of the L: - to
      the D: -form of an amino acid residue around the N/C-termini of substrate
      peptides. To date, some peptide isomerases have been found in a limited number of
      animal secretions and cells. We show here that papaya extracts have weak peptide
      isomerase activity. The activity was detected in each 30-100 kDa fraction of the
      flesh and the seed extracts of unripe and ripe papaya fruit. The definitive
      activity was confirmed in the ripe papaya extracts, but even then it was much
      less active than that of the other peptide isomerases previously reported. The
      activity was markedly inhibited by methanol, and partly so by amastatin and
      diethyl pyrocarbonate. This is the first report of peptide isomerase activity in
      a plant and suggests that perhaps every living organism may have some peptide
      isomerase activity.

PMID- 22648683
TI  - In vivo detoxification of furfural during lipid production by the oleaginous
      yeast Trichosporon fermentans.
AB  - In vivo detoxification of furfural by the oleaginous yeast, Trichosporon
      fermentans, under lipid-producing (i.e., nitrogen-limited) conditions was
      evaluated for the first time. During the initial fermentation phase, furfural was
      rapidly reduced to furfuryl alcohol, which is more toxic to T. fermentans than
      furfural. Furfuryl alcohol was subsequently oxidized to furoic acid which has low
      toxicity to T. fermentans and is the end product of the in vivo detoxification of
      furfural in this organism. These observations explain how T. fermentans can grow
      and accumulate lipids in medium containing furfural. They also indicate that
      strategies to minimize the transient production of furfuryl alcohol could further
      improve the capacity of the strain to produce lipids from furfural-containing
      lignocellulosic hydrolysates.

PMID- 22648684
TI  - Production of rare ginsenosides (compound Mc, compound Y and aglycon
      protopanaxadiol) by beta-glucosidase from Dictyoglomus turgidum that hydrolyzes
      beta-linked, but not alpha-linked, sugars in ginsenosides.
AB  - Optimal hydrolytic activity of beta-glucosidase from Dictyoglomus turgidum for
      the ginsenoside Rd was at pH 5.5 and 80  degrees C, with a half-life of ~11 h.
      The enzyme hydrolysed beta-linked, but not alpha-linked, sugar moieties of
      ginsenosides. It produced the rare ginsenosides, aglycon protopanaxadiol (APPD),
      compounds Y, and Mc, via three unique transformation pathways: Rb(1) -> Rd ->
      F(2) -> compound K -> APPD, Rb(2) -> compound Y, and Rc -> compound Mc. The
      enzyme converted 0.5 mM Rb(2) and 0.5 mM Rc to 0.5 mM compound Y and 0.5 mM
      compound Mc after 3 h, respectively, with molar conversion yields of 100 %.

PMID- 22648685
TI  - Expression and bioconversion of recombinant m- and p-hydroxybenzoate hydroxylases
      from a novel moderate halophile, Chromohalobacter sp.
AB  - p-Hydroxybenzoate hydroxylase (pobA) and m-hydroxybenzoate hydroxylase (mobA)
      genes, from the moderate halophile Chromohalobacter sp. HS-2, were expressed and
      characterized. Solubilities of overexpressed recombinant MobA and PobA were
      enhanced by the induction of the heat-shock proteins DnaJ and DnaK. Each MobA and
      PobA maintained stable activity under high NaCl concentrations. V (max) and K (m)
      values for MobA with m-hydroxybenzoate were 70 MUmol min(-1) mg(-1) protein and
      81 MUM, respectively. Similarly, those of PobA with p-hydroxybenzoate as
      substrate were 5 MUmol min(-1) mg(-1) protein and 129 MUM, respectively. The
      Escherichia coli expression system, including induction of heat shock proteins,
      was used to convert hydroxybenzoates into protocatechuate (3,4-dihydroxybenzoate)
      and revealed that resting cells harboring mobA converted 15 mM m-hydroxybenzoate
      to 15 mM protocatechuate while those harboring pobA converted 50 mM p
      hydroxybenzoate to 35 mM protocatechuate at 30  degrees C, respectively.

PMID- 22648686
TI  - Construction of self-cloning, indigenous wine strains of Saccharomyces cerevisiae
      with enhanced glycerol and glutathione production.
AB  - To improve wine taste and flavor stability, a novel indigenous strain of
      Saccharomyces cerevisiae with enhanced glycerol and glutathione (GSH) production
      for winemaking was constructed. ALD6 encoding an aldehyde dehydrogenases of the
      indigenous yeast was replaced by a GPD1 and CUP1 gene cassette, which are
      responsible for NAD-dependent glycerol-3-phosphatase dehydrogenase and copper
      resistance, respectively. Furthermore, the alpha-acetohydroxyacid synthase gene
      ILV2 of the indigenous yeast was disrupted by integration of the GSH1 gene which
      encodes gamma-glutamylcysteine synthetase and the CUP1 gene cassette. The
      fermentation capacity of the recombinant was similar to that of the wild-type
      strain, with an increase of 21 and 19 % in glycerol and GSH production. No
      heterologous DNA was harbored in the recombinant in this study.

PMID- 22648687
TI  - Changing the specificity of alpha-amino acid ester hydrolase toward para-hydroxyl
      cephalosporins synthesis by site-directed saturation mutagenesis.
AB  - alpha-Amino acid ester hydrolases (AEHs) catalyze the synthesis of beta-lactam
      antibiotics containing an alpha-amino group with decreased activity toward
      antibiotics with a p-hydroxyl group. The AEH gene from Xanthomonas rubrillineans
      was cloned and expressed in Escherichia coli. Based on the crystal structure of
      the AEH and cefprozil complex, 13 residues not directly involved in substrate
      recognition were mutated individually. The resulting ~1,300 mutants were screened
      for activity using cefprozil as a model product based on spectrophotometric assay
      in a 96-well format. Mutants with improved cefprozil synthetic activity revealed
      the particular importance of positions 87, 131 and 175 for specificity. The
      mutant V131S with the highest initial rates of synthesis toward three p-hydroxyl
      cephalosporins showed 23 %, 17 % and 64 % increase in maximum product
      accumulation of cefadroxil, cefprozil and cefatrizine, respectively.

PMID- 22648688
TI  - Integrated microspectrometer for fluorescence based analysis in a microfluidic
      format.
AB  - We have demonstrated a monolithic integrated arrayed waveguide grating (AWG)
      microspectrometer microfluidic platform capable of fluorescence spectroscopic
      analysis. The microspectrometer in this proof of concept study has a small (1 cm
      * 1 cm) footprint and 8 output channels centred on different wavelengths. We show
      that the signals from the output channels detected on a camera chip can be used
      to recreate the complete fluorescence spectrum of an analyte. By making
      fluorescence measurements of (i) mixed quantum dot solutions, (ii) an organic
      fluorophore (Cy5) and (iii) the propidium iodide (PI)-DNA assay, we illustrate
      the unique advantages of the AWG platform for simultaneous, quantitative
      multiplex detection and its capability to detect small spectroscopic shifts.
      Although the current system is designed for fluorescence spectroscopic analysis,
      in principle, it can be implemented for other types of analysis, such as Raman
      spectroscopy. Fabricated using established semiconductor industry methods, this
      miniaturised platform holds great potential to create a handheld, low cost
      biosensor with versatile detection capability.

PMID- 22648689
TI  - The effect of genetically modified Lactobacillus plantarum 590 on the gut health
      of Sprague-Dawley rats.
AB  - Lp was a generally recognized as safe microorganism. Lactobacillus plantarum 590
      was obtained by inserting nisI gene into Lp genome to help it tolerate higher
      concentration nisin. As the unintended effects of the genetically modified
      microorganism (GMM) are the most important barriers to the progress of GMM, we
      have performed a useful exploration to establish a new in vivo evaluation model
      for GMM from the point of view of intestinal health. In this study, Sprague
      Dawley rats were orally administered with Lp 590 and Lp for 4 weeks. Fecal
      samples were collected to determine the number of beneficial bacteria
      Bifidobacterium and harmful bacteria Clostridium perfringens. Denaturing gradient
      gel electrophoresis was used to detect the bacterial profiles of every group.
      Fecal enzyme activities and short-chain fatty acids as main metabolites were also
      examined. Real time PCR (RT-PCR) and immunohistochemistry were used to analyze
      two proteins (ZO-1 and occludin) and secretory immunoglobulin A to detect
      intestinal permeability and mucosal immunity, gut permeability and gut mucosal
      immunity were analyzed to see whether GM Lp 590 can induce changes of the gut
      health when compared with non-GM Lp group, andeventually we concluded that there
      is no significant difference between GM Lp 590-fed group and non-GM Lp-fed group.
      The conclusion of gut health test was comparable withthat from traditional
      subchronic test. Evaluation of intestinal health will be a new approach of
      assessing the safety of GMM.

PMID- 22648691
TI  - Response surface methodology for optimizing the bovine serum albumin
      fibrillation.
AB  - Amyloid fibrils are considered as nanostructures that could be formed by ordered
      self-assembly of the partially-folded states of many different peptides or
      proteins. In this study, bovine serum albumin was used as a model protein whose
      ordered aggregation (fibrillation) was optimized. Response surface methodology
      (RSM) was used in a design that contained a total of 30 experimental trials. The
      first 24 were organized in a factorial design and from 25 to 30 involved the
      replications of the central points. Data obtained from RSM were subjected to the
      analysis of variance (ANOVA) and analyzed using a second order polynomial
      equation. Subsequent testing of the suggested experimental parameters was done in
      vitro with Congo red spectrophotometric assay. Protein concentration, pH,
      temperature and time of incubation were the variables used in this study.
      Responses were assessed by measuring absorbance in 540 nm (characteristic of
      amyloid formation) and maximal wavelength. Concomitant effects of variables were
      assessed in surface plots that each considered two of the variables.
      Interestingly, the pattern obtained by monitoring absorbance at 540 nm and
      absorbance in maximal wavelength were identical in most cases. We are reporting
      the optimum concentration of protein, pH, temperature and time at 5 mg ml-1, 3.02
      and 72  degrees C and 48 h, respectively. Our findings suggest that use of Congo
      red spectrophotometric test, as a simple and affordable assay could be suggested
      as a first test for assessing fibril formation of proteins. Absorbance in maximal
      wavelength is recommended as a significant indication of fibril formation.

PMID- 22648692
TI  - Complete amino acid sequence of globin chains and biological activity of
      fragmented crocodile hemoglobin (Crocodylus siamensis).
AB  - Hemoglobin, alpha-chain, beta-chain and fragmented hemoglobin of Crocodylus
      siamensis demonstrated both antibacterial and antioxidant activities.
      Antibacterial and antioxidant properties of the hemoglobin did not depend on the
      heme structure but could result from the compositions of amino acid residues and
      structures present in their primary structure. Furthermore, thirteen purified
      active peptides were obtained by RP-HPLC analyses, corresponding to fragments in
      the alpha-globin chain and the beta-globin chain which are mostly located at the
      N-terminal and C-terminal parts. These active peptides operate on the bacterial
      cell membrane. The globin chains of Crocodylus siamensis showed similar amino
      acids to the sequences of Crocodylus niloticus. The novel amino acid
      substitutions of alpha-chain and beta-chain are not associated with the heme
      binding site or the bicarbonate ion binding site, but could be important through
      their interactions with membranes of bacteria.

PMID- 22648693
TI  - YspC: a unique translocator exhibits structural alteration in the complex form
      with chaperone SycB.
AB  - YspC is an annotated translocator of Yersinia secretion apparatus-Yersinia
      secretion protein type three secretion system of Yersinia enterocolitica, it
      forms an 1:1 complex with its cognate chaperone SycB. Unlike other translocators,
      YspC is highly soluble inspite of having a transmembrane region. Size exclusion
      chromatography shows that YspC exists predominantly in a monomeric form. Multiple
      sequence alignment and ConSurf (a web based bioinformatic tool) analysis confirm
      its significant deviation from the closest class of minor translocators. YspC
      also possesses a tertiary structure signal seen from near UV CD, further
      confirming its unique nature amongst the groups of translocators. Far UV CD
      depicts that YspC is predominantly an alpha-helical protein; however, its
      secondary structure alters in the YspC-SycB complex. Thermal denaturation curve
      predicts a cooperative melting behaviour for YspC which is altered in the YspC
      SycB complex. Furthermore, trypsinolysis data confirms a different digestion
      pattern for YspC in isolation, when compared to the complex form with SycB. From
      the Forsters resonance energy transfer analysis, it can be predicted that the two
      tetratricopeptide repeat regions of SycB are masked while it forms a complex with
      YspC and this is further confirmed by the interaction studies of YspC with two
      truncated forms of SycB. YspC interacted with ?SycB1-114 and ?SycB36-114
      (possessing only the two TPR regions). However, the complexes formed between YspC
      and truncated forms of SycB have altered physiological states.

PMID- 22648694
TI  - CUE: the continuous unified electronic diary method.
AB  - In the present article, we introduce the continuous unified electronic (CUE)
      diary method, a longitudinal, event-based, electronic parent report method that
      allows real-time recording of infant and child behavior in natural contexts.
      Thirty-nine expectant mothers were trained to identify and record target
      behaviors into programmed handheld computers. From birth to 18 months, maternal
      reporters recorded the initial, second, and third occurrences of seven target
      motor behaviors: palmar grasp, rolls from side to back, reaching when sitting,
      pincer grip, crawling, walking, and climbing stairs. Compliance was assessed as
      two valid entries per behavior: 97 % of maternal reporters met compliance
      criteria. Reliability was assessed by comparing diary entries with researcher
      assessments for three of the motor behaviors: palmar grasp, pincer grip and
      walking. A total of 81 % of maternal reporters met reliability criteria. For
      those three target behaviors, age of emergence was compared across data from the
      CUE diary method and researcher assessments. The CUE diary method was found to
      detect behaviors earlier and with greater sensitivity to individual differences.
      The CUE diary method is shown to be a reliable methodological tool for studying
      processes of change in human development.

PMID- 22648696
TI  - Multilevel meta-analysis of single-subject experimental designs: a simulation
      study.
AB  - One way to combine data from single-subject experimental design studies is by
      performing a multilevel meta-analysis, with unstandardized or standardized
      regression coefficients as the effect size metrics. This study evaluates the
      performance of this approach. The results indicate that a multilevel meta
      analysis of unstandardized effect sizes results in good estimates of the effect.
      The multilevel meta-analysis of standardized effect sizes, on the other hand, is
      suitable only when the number of measurement occasions for each subject is 20 or
      more. The effect of the treatment on the intercept is estimated with enough power
      when the studies are homogeneous or when the number of studies is large; the
      power of the effect on the slope is estimated with enough power only when the
      number of studies and the number of measurement occasions are large.

PMID- 22648695
TI  - It depends on how you look at it: scanpath comparison in multiple dimensions with
      MultiMatch, a vector-based approach.
AB  - Eye movement sequences-or scanpaths-vary depending on the stimulus
      characteristics and the task (Foulsham & Underwood Journal of Vision, 8(2), 6:1
      17, 2008; Land, Mennie, & Rusted, Perception, 28, 1311-1328, 1999). Common
      methods for comparing scanpaths, however, are limited in their ability to capture
      both the spatial and temporal properties of which a scanpath consists. Here, we
      validated a new method for scanpath comparison based on geometric vectors, which
      compares scanpaths over multiple dimensions while retaining positional and
      sequential information (Jarodzka, Holmqvist, & Nystrom, Symposium on Eye-Tracking
      Research and Applications (pp. 211-218), 2010). "MultiMatch" was tested in two
      experiments and pitted against ScanMatch (Cristino, Mathot, Theeuwes, &
      Gilchrist, Behavior Research Methods, 42, 692-700, 2010), the most comprehensive
      adaptation of the popular Levenshtein method. In Experiment 1, we used synthetic
      data, demonstrating the greater sensitivity of MultiMatch to variations in
      spatial position. In Experiment 2, real eye movement recordings were taken from
      participants viewing sequences of dots, designed to elicit scanpath pairs with
      commonalities known to be problematic for algorithms (e.g., when one scanpath is
      shifted in locus or when fixations fall on either side of an AOI boundary). The
      results illustrate the advantages of a multidimensional approach, revealing how
      two scanpaths differ. For instance, if one scanpath is the reverse copy of
      another, the difference is in the direction but not the positions of fixations;
      or if a scanpath is scaled down, the difference is in the length of the saccadic
      vectors but not in the overall shape. As well as having enormous potential for
      any task in which consistency in eye movements is important (e.g., learning),
      MultiMatch is particularly relevant for "eye movements to nothing" in mental
      imagery and embodiment-of-cognition research, where satisfactory scanpath
      comparison algorithms are lacking.

PMID- 22648697
TI  - Combined modality treatment for patients with locally advanced pancreatic
      adenocarcinoma.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is an emerging treatment for patients
      with locally advanced pancreatic carcinoma, and can be combined with
      radiochemotherapy and intra-arterial plus systemic chemotherapy. METHODS: This
      observational study compared two groups of patients with locally advanced
      pancreatic carcinoma treated with either primary RFA (group 1) or RFA following
      any other primary treatment (group 2). RESULTS: Between February 2007 and May
      2010, 107 consecutive patients were treated with RFA. There were 47 patients in
      group 1 and 60 in group 2. Median overall survival was 25.6 months. Median
      overall survival was significantly shorter in group 1 than in group 2 (14.7
      versus 25.6 months; P = 0.004) Patients treated with RFA, radiochemotherapy and
      intra-arterial plus systemic chemotherapy (triple-approach strategy) had a median
      overall survival of 34.0 months. CONCLUSION: RFA after alternative primary
      treatment was associated with prolonged survival. This was further extended by
      use of a triple-approach strategy in selected patients. Further evaluation of
      this approach seems warranted.

PMID- 22648699
TI  - Assessing the reliability and quality of online uterine fibroid embolization
      resources.
AB  - PURPOSE: This study was designed to examine the best internet resources about
      uterine fibroid embolization (UFE) pertinent to medical trainees, radiologists,
      gynecologists, family physicians, and patients. METHODS: The terms "uterine
      fibroid embolization," "uterine fibroid embolization," and "uterine artery
      embolization" were entered into Google, Yahoo, and Bing search engines; the top
      20 hits were assessed. The hits were categorized as organizational or
      nonorganizational. Additionally, 23 radiological and obstetrical organizations
      were assessed. The DISCERN instrument and Journal of the American Medical
      Association (JAMA) benchmarks (authorship, attribution, currency, disclosure)
      were used to assess the information critically. The scope, strength, weaknesses,
      and unique features were highlighted for the top five organizational and
      nonorganizational websites. RESULTS: A total of 203 websites were reviewed; 23
      were removed in accordance with the exclusion criteria and 146 were duplicate
      websites, for a total of 34 unique sites. It was found that 35 % (12/34 websites)
      were organizational (family medicine, radiology, obstetrics/gynecology) and 65 %
      (22/34 websites) were nonorganizational (teaching or patient resources). The
      overall mean DISCERN score was 49.6 (10.7). Two-tailed, unpaired t test
      demonstrated no statistically significant difference between organizational and
      nonorganizational websites (p = 0.101). JAMA benchmarks revealed 44 % (15/34
      websites) with authorship, 71 % (24/34 websites) with attribution, 68 % (23/34
      websites) with disclosure, and 47 % (16/34 websites) with currency. CONCLUSIONS:
      The overall quality of websites for UFE is moderate, with important but not
      serious shortcomings. The best websites provided relevant information about the
      procedure, benefits/risks, and were interactive. DISCERN scores were compromised
      by sites failing to provide resources for shared decision-making, additional
      support, and discussing consequence of no treatment. JAMA benchmarks revealed
      lack of authorship and currency.

PMID- 22648698
TI  - Extrahepatic pseudoaneurysms and ruptures of the hepatic artery in liver
      transplant recipients: endovascular management and a new iatrogenic etiology.
AB  - PURPOSE: To characterize extrahepatic pseudoaneurysm regarding incidence and
      etiology and determine the effectiveness of endovascular management. METHODS: A
      retrospective audit of 1,857 liver transplants in two institutions was performed
      (1996-2009). Recipients' demographics, clinical presentation, transplant type,
      biliary anastomosis, and presence of biliary endoprostheses were noted.
      Pseudoaneurysms were classified into iatrogenic (associated with biliary
      endoprosthesis or angioplasty) or spontaneous extrahepatic pseudoaneurysms.
      Spontaneous and iatrogenic pseudoaneurysms were compared for time from
      transplant, presenting symptoms, location in the arterial anatomy, and 3-month
      graft survival. Arterial patency and 6-month graft survival were calculated.
      RESULTS: Twenty pseudoaneurysms were found (1.1 %, 20/1,857): 9 (0.5 % of
      transplants, 9/1,857) were spontaneous and 11 (0.6 % of transplants, 11/1,857)
      were "iatrogenic" (due to minimally invasive procedures: 4 angioplasty and 7
      biliary endoprostheses). Sixty percent (12/20) underwent endovascular management
      (4 coil embolization and 8 stent-grafts). Technical success was 83 % (10/12) with
      a mean arterial patency of 70 % (follow-up mean, 4.9; range, 0-18 months). The 1
      , 3-, and 6-month graft survival was 70, 40, and 35 %, respectively. CONCLUSIONS:
      Due to minimally invasive procedures, posttransplant extrahepatic pseudoaneurysms
      are no longer an exclusive complication of the transplant surgery itself.
      Endovascular management is effective to stabilize patients but has not improved
      historic postsurgical graft survival.

PMID- 22648700
TI  - Quality-improvement guidelines for hepatic transarterial chemoembolization.

PMID- 22648701
TI  - Investigation of the PSF-choice method for reduced lipid contamination in
      prostate MR spectroscopic imaging.
AB  - The purpose of this work was to evaluate a previously proposed approach that aims
      to improve the point spread function (PSF) of MR spectroscopic imaging (MRSI) to
      avoid corruption by lipid signal arising from neighboring voxels. Retrospective
      spatial filtering can be used to alter the PSF; however, this either reduces
      spatial resolution or requires extending the acquisition in k-space at the cost
      of increased imaging time. Alternatively, the method evaluated here, PSF-choice,
      can modify the PSF localization to reduce the contamination from adjacent lipids
      by conforming the signal response more closely to the desired MRSI voxel grid.
      This is done without increasing scan time or degrading SNR of important
      metabolites. PSF-choice achieves improvements in spatial localization through
      modifications to the radiofrequency excitation pulses. An implementation of this
      method is reported for MRSI of the prostate, where it is demonstrated that, in 13
      of 16 pilot prostate MRSI scans, intravoxel spectral contamination from lipid was
      significantly reduced when using PSF-choice. Phantom studies were also performed
      that demonstrate, compared with MRSI with standard Fourier phase encoding, out-of
      voxel signal contamination of spectra was significantly reduced in MRSI with PSF
      choice.

PMID- 22648702
TI  - Impact of psychosis on Portuguese caregivers: a cross-cultural exploration of
      burden, distress, positive aspects and clinical-functional correlates.
AB  - PURPOSE: Further cross-cultural comparisons are needed on caregiving consequences
      of chronic psychotic disorders. The EPSILON study (European Psychiatric Services:
      Inputs Linked to Outcome Domains and Needs) involved five European countries, but
      not Portugal. We aimed to analyse the impact of severe mental illness in a
      Portuguese sample and to provide support to comparisons with some of the EPSILON
      results, focusing on the north-European Dutch centre. METHODS: We studied 108
      caregiver-patient dyads by a consecutive sampling of people with schizophrenia
      spectrum disorders in psychiatric outpatient services. Relatives' assessments
      included the Involvement Evaluation Questionnaire, European version (IEQ), the 12
      item General Health Questionnaire (GHQ-12); the loss, stigma and positive
      aspects' subscales of the Experience of Caregiving Inventory, and the Social
      Network and Family Coping Questionnaires. Patients were assessed regarding
      symptoms, disability and global functioning. RESULTS: Caregiving rewards and
      negative consequences co-existed. On the IEQ, 49.1% reported negative
      consequences and rank order of domain scores was worrying > urging > tension >
      supervision. More than one-third of caregivers were psychologically distressed
      according to GHQ screenings. Involvement Evaluation Questionnaire scores were
      correlated with caregivers' distress, stigma, loss, patient's involvement and
      other ways of coping, and patients' variables. Some of these failed to be
      included in a regression model. CONCLUSIONS: Many of these Portuguese caregivers
      were at risk regarding burden and psychological distress. In comparison with
      other European samples, caregiving arrangements and assessments were typical of
      Mediterranean countries, as Italy or Spain. All IEQ scores were significantly
      higher than those in the Netherlands. On account of small numbers, caution is
      needed in the interpretation of associations.

PMID- 22648703
TI  - Intervention effectiveness among war-affected children: a cluster randomized
      controlled trial on improving mental health.
AB  - We examined the effectiveness of a psychosocial intervention in reducing mental
      health symptoms among war-affected children, and the role of peritraumatic
      dissociation in moderating the intervention impact on posttraumatic stress
      symptoms (PTSS). School classes were randomized into intervention (n = 242) and
      waitlist control (n = 240) conditions in Gaza, Palestine. The intervention group
      participated in 16 extracurriculum sessions of teaching recovery techniques (TRT)
      and the controls received normal school-provided support. Participants were 10-
      to 13-year-old Palestinian girls (49.4%) and boys (50.6%). Data on PTSS,
      depressive symptoms, and psychological distress were collected at baseline (T1),
      postintervention (T2), and 6-month follow-up (T3). Peritraumatic dissociation was
      assessed only at baseline. Regression analyses that took regression to the mean
      and cluster sampling into account were applied. The results on intervention
      effectiveness were specific to gender and peritraumatic dissociation. At T2, the
      intervention significantly reduced the proportion of clinical PTSS among boys,
      and both the symptom level (R(2)  = .24), and proportion of clinical PTSS among
      girls who had a low level of peritraumatic dissociation. The results have
      implications for risk-specific tailoring of psychosocial interventions in war
      conditions.

PMID- 22648704
TI  - Transvaginal sonography in diagnosis of vesicoperitoneal fistula due to deep
      infiltrating endometriosis as a cause of uroperitoneum.

PMID- 22648705
TI  - Long-term results (>25 years) of a randomized, prospective clinical trial
      evaluating chemotherapy in patients with high-grade, operable osteosarcoma.
AB  - BACKGROUND: The authors present the long-term follow-up (>25 years) data from 1
      of the original prospective, randomized trials that compared adjuvant
      chemotherapy with expectant management in patients with high-grade, localized
      osteosarcoma. In addition, the value of pathologic necrosis induced by a single
      cycle of neoadjuvant chemotherapy was analyzed as a predictive marker of disease
      free and overall survival. METHODS: Fifty-nine patients with high-grade,
      localized osteosarcoma were enrolled in a prospective trial that was performed
      between 1981 and 1984 at the University of California-Los Angeles (UCLA).
      Patients were randomized to receive either adjuvant chemotherapy or observation
      after surgical resection. Long-term outcomes, follow-up, and pathologic review of
      all available histologic sections were performed. RESULTS: The 25-year disease
      free survival rate was 28% for patients who received adjuvant chemotherapy
      compared with 15% for the untreated patients (P = .02). The overall survival rate
      at 25 years was also significantly higher for treated patients versus untreated
      patients (38% vs 15%; P = .02). Tumor necrosis >90% after a single round of
      chemotherapy was a statistically significant predictor of overall survival and
      disease-free survival for patients who received adjuvant therapy (164 months vs
      65 months [P = .04] and 141 months vs 14 months [P < .01], respectively).
      CONCLUSIONS: Patients with high-grade, localized osteosarcoma who received
      adjuvant chemotherapy after undergoing definitive surgical resection had a
      statistically significant benefit in disease-free and overall survival that was
      maintained through 25 years. Tumor necrosis after just 1 cycle of neoadjuvant
      chemotherapy and radiation was predictive of overall survival and disease-free
      survival in patients who received adjuvant chemotherapy.

PMID- 22648706
TI  - Functionalization of polycarbonate with proteins; open-tubular enzymatic
      microreactors.
AB  - This paper examines a set of techniques for the immobilization of enzymes on the
      surface of microchannels fabricated in polycarbonate (PC). Our experiments
      identify the method that uses combined physico-chemical immobilization on a layer
      of polyethyleneimine (PEI) as a reproducible vista for the robust immobilization
      of proteins. As an example, we demonstrate the fabrication, throughput and
      stability of an open-tubular reactor draped with alkaline phosphatase (ALP, EC
      3.1.3.1) as a model enzyme. As PC is suitable for industrial applications the
      method could potentially be used to immobilize proteins in numbered-up
      implementations.

PMID- 22648708
TI  - FGFR1 expression and gene copy numbers in human lung cancer.
AB  - FGFR1 is a receptor tyrosine kinase of which the ligands belong to the fibroblast
      growth factor family. To evaluate the significance of FGFR1 in lung cancer, we
      analysed tumours by immunohistochemistry (IHC) and fluorescence in situ
      hybridization (FISH). Tissue microarrays were constructed containing 380 lung
      cancer samples including squamous cell carcinomas (SCC), adenocarcinomas (ADC),
      non-small cell lung cancer not otherwise specified, metastases, neuroendocrine
      tumours, large cell lung cancer and small cell lung cancer. FGFR1 expression was
      analysed by IHC and scored semi-quantitatively by a four-tier approach (0, 1, 2,
      3). Using dual-colour interphase FISH with probes specific for the locus on 8p12
      and the centromere of chromosome 8 (CEN8), copy numbers of FGFR1 were determined.
      High expression of FGFR1 was associated with increased FGFR1 gene copy numbers in
      squamous cell carcinoma (p < 0.001). The FGFR1 locus was equally affected by copy
      number losses and gains. The higher FGFR1 gene copy numbers in SCC compared to
      ADC did not reach statistical significance. High copy number amplification of
      FGFR1 was a very rare event, the FGFR1/CEN8 signal ratio reaching a maximum value
      of 2.75. There were no significant associations between FGFR1 and
      clinicopathological parameters. Fibroblast growth factor signalling represents an
      interesting therapeutic target in lung cancer. However, the pathways are complex
      with potential oncogenic and anti-oncogenic activities. Our data may help to
      define criteria for selecting patients that may benefit from these new
      therapeutic options.

PMID- 22648709
TI  - Effect of alginate supplementation on weight loss in obese subjects completing a
      12-wk energy-restricted diet: a randomized controlled trial.
AB  - BACKGROUND: Acute studies with alginate-based preloads suggested that these
      strong gelling fibers may induce increased feelings of satiety and reduce energy
      intakes. However, the long-term efficacy and safety of alginate supplementation
      on body weight regulation are lacking. OBJECTIVE: The primary aim of the study
      was to investigate the effects in subjects of alginate supplementation in
      conjunction with energy restriction (-300 kcal/d) on loss of body weight and fat
      and, second, on metabolic risk markers in comparison with in a placebo group.
      DESIGN: In a parallel, double-blind, placebo-controlled study, we randomly
      assigned 96 obese subjects to either an energy-restricted diet plus a placebo
      preload supplement or an energy-restricted diet plus an alginate-based preload
      supplement (15 g fiber). The preload was administered as a beverage 3 times/d
      before main meals for a period of 12 wk. RESULTS: No differences in loss of body
      weight and fat between groups were shown in the intension-to-treat (ITT) analysis
      (P > 0.1). However, in the completer analysis (n = 80), we showed a greater
      weight loss with alginate (6.78 +/- 3.67 kg) than with the placebo (5.04 +/- 3.40
      kg) (P = 0.03), which was mainly attributed to a reduction in the percentage of
      body fat (P = 0.03). In the ITT analysis, a larger decrease in systolic and
      diastolic blood pressure was shown in the placebo group than in the alginate
      group (P < 0.05). Plasma concentrations of glucose, insulin, C-reactive protein,
      and ghrelin, HOMA-IR, and lipid metabolism did not differ between treatment
      groups in the ITT analysis (P > 0.1). CONCLUSION: These results suggest that
      alginate supplementation as an adjunct to energy restriction may improve weight
      loss in obese subjects who complete a 12-wk dietary intervention.

PMID- 22648710
TI  - CYP1A2 and coffee intake and the modifying effect of sex, age, and smoking.
AB  - BACKGROUND: The enzyme CYP1A2 (cytochrome 1A2) is involved in the metabolism of
      certain drugs and caffeine, and its activity can be influenced by factors such as
      sex, age, and smoking. The single nucleotide polymorphism (SNP) rs762551A>C,
      which has also been studied for its modifying effect on cardiovascular disease,
      has been reported to alter enzyme activity. OBJECTIVE: The objective was to study
      the effect of CYP1A2, sex, age, and smoking on coffee intake. DESIGN: Within the
      Rotterdam Study, a population-based cohort, all coffee drinkers for whom genome
      wide association data were available were selected. Because SNP rs762551 was not
      on the Illumina 550 platform, SNP rs2472299 was used as a proxy, with the A
      allele of rs762551 linked to the G allele of rs2472299. Linear regression
      analyses were used to determine the effect and interaction of rs2472299, sex,
      age, and smoking on coffee intake. Adjusted geometric means of coffee intake were
      calculated per genotype for the different smoking and sex strata by using
      multivariable general linear models. A combined analysis, with the use of a "risk
      score," was performed to determine the contribution of each separate factor.
      RESULTS: rs2472299G>A, female sex, and nonsmoking were significantly inversely
      related to coffee intake. Coffee intake was lowest in nonsmoking women homozygous
      for rs2472299G>A (3.49 cups/d; ~436 mL). All factors contributed almost linearly
      to the intake of coffee, with the highest coffee intake in smoking men without
      the A allele (5.32 cups/d; ~665 mL). CONCLUSION: rs2472299G>A, linked to
      rs762551A>C, sex, age, and smoking significantly contribute to coffee intake.

PMID- 22648711
TI  - Selenium and prostate cancer: systematic review and meta-analysis.
AB  - BACKGROUND: Prostate cancer is a growing public health problem. Several human
      studies have shown a potentially protective effect of selenium, but the
      conclusions from published reports are inconsistent. OBJECTIVE: The objective was
      to examine the evidence for relations between selenium intake, selenium status,
      and prostate cancer risk. DESIGN: This was a systematic review and meta-analysis
      of randomized controlled trials, case-control studies, and prospective cohort
      studies. The World Cancer Research Fund/American Institute for Cancer Research
      Continuous Update Project database was searched up to September 2010. The studies
      included reported measurements of selenium intake or status (plasma, serum, or
      toenail selenium), assessments of prostate cancer cases (number of events), and
      the RR in the adult population. Meta-analyses were performed, and study quality,
      heterogeneity, and small study effects were assessed. Dose-response meta-analyses
      were used, with restricted cubic splines and fractional polynomials for nonlinear
      trends, to investigate the association between selenium status and prostate
      cancer risk. RESULTS: Twelve studies with a total of 13,254 participants and 5007
      cases of prostate cancer were included. The relation between plasma/serum
      selenium and prostate cancer in a nonlinear dose-response meta-analysis showed
      that the risk decreased with increasing plasma/serum selenium up to 170 ng/mL.
      Three high-quality studies included in the meta-analysis of toenail selenium and
      cancer risk indicated a reduction in prostate cancer risk (estimated RR: 0.29;
      95% CI: 0.14, 0.61) with a toenail selenium concentration between 0.85 and 0.94
      MUg/g. CONCLUSION: The relation between selenium status and decreased prostate
      cancer risk was examined over a relatively narrow range of selenium status;
      further studies in low-selenium populations are required.

PMID- 22648712
TI  - Rapid alternative absorption of dietary long-chain fatty acids with upregulation
      of intestinal glycosylated CD36 in liver cirrhosis.
AB  - BACKGROUND: Dietary long-chain fatty acid (LCFA) intake is an important risk
      factor for hepatic inflammation and hepatocarcinogenesis. An alternate route of
      dietary LCFA absorption has been suggested in patients with liver cirrhosis (LC).
      OBJECTIVE: We aimed to determine this alternate route and to identify its
      mechanism. DESIGN: Twenty healthy control subjects and 47 patients with LC-n = 23
      with portal hypertension [PH(+)LC] and 24 without portal hypertension [PH(-)LC)]
      were enrolled. [13C]Palmitate (an LCFA) and octanoate (a medium-chain fatty acid
      [MCFA]) were administered by using gastrointestinal endoscopy. Breath 13CO2 was
      measured to quantify metabolized fatty acids. We also examined intestinal
      specimens of patients in these groups. RESULTS: A more rapid increase in
      metabolized palmitate, which showed a pattern similar to that of octanoate
      metabolism, was observed in patients with LC than in healthy control subjects.
      The increase in the PH(-)LC group was higher than that in the PH(+)LC group.
      However, the concentration of metabolized palmitate increased with treatment of
      the PH(+)LC group with a portal-systemic shunt. Morphologic changes such as
      expanded lymph and blood vessels were present, and glycosylated CD36 increased in
      the jejunum of the PH(+)LC group. This group had high serum concentrations of
      glucagon-like peptide-2. These data suggest that dietary LCFAs, similar to MCFAs,
      are absorbed via blood vessels in patients with LC. CONCLUSIONS: Rapid absorption
      of LCFAs by an alternative method occurred in patients with LC. This altered LCFA
      processing is likely related to upregulation of intestinal glycosylated CD36 and
      could contribute to pathogenesis in patients with LC.

PMID- 22648713
TI  - Maternal vitamin D predominates over genetic factors in determining neonatal
      circulating vitamin D concentrations.
AB  - BACKGROUND: There are multiple potential regulators of neonatal vitamin D status
      of environmental, genetic, and epigenetic origins. The relation between these
      factors and circulating neonatal vitamin D has yet to be fully characterized.
      OBJECTIVE: The aim of this study was to examine the relative contribution of
      genetic factors, maternal circulating 25-hydroxyvitamin D [25(OH)D]
      concentrations, and the placental methylation level of the gene that encodes the
      primary catabolic enzyme of active vitamin D [25(OH)D-24-hydroxylase encoded by
      CYP24A1] to neonatal 25(OH)D concentrations. DESIGN: We used the classical twin
      study design to determine the genetic contribution to neonatal 25(OH)D. A total
      of 86 twin pairs (32 monozygotic and 54 dizygotic twin pairs) were included in
      this study. Serum 25(OH)D was measured by using a 25(OH)D kit. CYP24A1 promoter
      DNA methylation was measured by means of matrix-assisted laser desorption time-of
      flight mass spectrometry. RESULTS: Maternal and neonatal 25(OH)D showed a strong
      association (R2 = 0.19). Monozygotic and dizygotic within-pair serum 25(OH)D
      correlations were similar (R2 = 0.71 and 0.67, respectively), which suggested no
      genetic effect. Placental CYP24A1 methylation did not show an association with
      maternal or neonatal 25(OH)D concentrations. CONCLUSIONS: Our results suggest
      that maternal circulating 25(OH)D is the most significant regulator of neonatal
      circulating 25(OH)D concentrations, with underlying genetic factors playing a
      limited role. The placental methylation of the CYP24A1 promoter appears subject
      to a genetic influence, although no evidence of a relation between the
      methylation level of this gene and circulating maternal or neonatal 25(OH)D was
      apparent.

PMID- 22648715
TI  - Dietary polyamine intake and risk of colorectal adenomatous polyps.
AB  - BACKGROUND: Putrescine, spermidine, and spermine are the polyamines required for
      human cell growth. The inhibition of ornithine decarboxylase (ODC), which is the
      rate-limiting enzyme of polyamine biosynthesis, decreases tumor growth and the
      development of colorectal adenomas. A database was developed to estimate dietary
      polyamine exposure and relate exposure to health outcomes. OBJECTIVE: We
      hypothesized that high polyamine intake would increase risk of colorectal adenoma
      and that the allelic variation at ODC G>A +316 would modify the association.
      DESIGN: Polyamine exposure was estimated in subjects pooled (n = 1164) from the
      control arms of 2 randomized trials for colorectal adenoma prevention [Wheat Bran
      Fiber low-fiber diet arm (n = 585) and Ursodeoxycholic Acid placebo arm (n =
      579)] by using baseline food-frequency questionnaire data. All subjects had to
      have a diagnosis of colorectal adenoma to be eligible for the trial. RESULTS: A
      dietary intake of polyamines above the median amount in the study population was
      associated with 39% increased risk of colorectal adenoma at follow-up (adjusted
      OR: 1.39; 95% CI: 1.06, 1.83) in the pooled sample. In addition, younger
      participants (OR: 1.94; 95% CI: 1.23, 3.08), women (OR: 2.43; 95% CI: 1.48,
      4.00), and ODC GG genotype carriers (OR: 1.59; 95% CI: 1.00, 2.53) had
      significantly increased odds of colorectal adenoma if they consumed above-median
      polyamine amounts. CONCLUSIONS: This study showed a role for dietary polyamines
      in colorectal adenoma risk. Corroboration of these findings would confirm a
      previously unrecognized, modifiable dietary risk factor for colorectal adenoma.

PMID- 22648714
TI  - Soy food intake after diagnosis of breast cancer and survival: an in-depth
      analysis of combined evidence from cohort studies of US and Chinese women.
AB  - BACKGROUND: Soy isoflavones have antiestrogenic and anticancer properties but
      also possess estrogen-like properties, which has raised concern about soy food
      consumption among breast cancer survivors. OBJECTIVE: We prospectively evaluated
      the association between postdiagnosis soy food consumption and breast cancer
      outcomes among US and Chinese women by using data from the After Breast Cancer
      Pooling Project. DESIGN: The analysis included 9514 breast cancer survivors with
      a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and
      1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food
      frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry
      Cox regression models, adjusted for sociodemographic, clinical, and lifestyle
      factors. RESULTS: After a mean follow-up of 7.4 y, we identified 1171 total
      deaths (881 from breast cancer) and 1348 recurrences. Despite large differences
      in soy isoflavone intake by country, isoflavone consumption was inversely
      associated with recurrence among both US and Chinese women, regardless of whether
      data were analyzed separately by country or combined. No heterogeneity was
      observed. In the pooled analysis, consumption of >=10 mg isoflavones/d was
      associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI:
      0.70, 1.10) and breast cancer-specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality
      and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI:
      0.61, 0.92). CONCLUSION: In this large study of combined data on US and Chinese
      women, postdiagnosis soy food consumption of >=10 mg isoflavones/d was associated
      with a nonsignificant reduced risk of breast cancer-specific mortality and a
      statistically significant reduced risk of recurrence.

PMID- 22648716
TI  - Modifying effects of alcohol on the postprandial glucose and insulin responses in
      healthy subjects.
AB  - BACKGROUND: Moderate alcohol consumption associates with lower risk of type 2
      diabetes, but in postprandial studies, alcohol induced impaired insulin
      sensitivity. The measurement of the glycemic index (GI) for beer has been
      considered challenging because of its low carbohydrate content. Therefore,
      imputed GI values from 36 to 95 on the basis of carbohydrate-rich beverages have
      been used for beer in epidemiologic studies. OBJECTIVES: We investigated the
      acute effects of alcohol on glucose and insulin responses and measured GIs and
      insulinemic indexes (IIs) of nonalcoholic and alcoholic beers. DESIGN: In a
      crossover design, 10 healthy volunteers were served beer with 4.5% alcohol by
      volume, nonalcoholic beer, and a glucose solution with alcohol once and the
      reference glucose solution twice. Each portion contained 25 g available
      carbohydrate, and the beer and glucose solution with alcohol contained 21 g
      alcohol. Capillary blood samples were collected up to 2 h after ingestion, and
      the incremental AUCs (IAUCs), GIs, and IIs were calculated. RESULTS: Compared
      with the reference glucose solution, the glucose solution with alcohol produced
      an 18% higher postprandial glucose IAUC (P = 0.03) and had no significant effect
      on the insulin IAUC. Compared with the reference glucose solution, beer had no
      significant effect on glucose or insulin IAUCs, and nonalcoholic beer tended to
      reduce the glucose IAUC (P = 0.06) but not the insulin IAUC. GIs of beer and
      nonalcoholic beer were 119 and 80, and IIs were 130 and 88, respectively.
      CONCLUSIONS: Alcohol increases the postprandial glucose response, probably
      through impaired insulin sensitivity. GI values published for alcohol-containing
      beers have underestimated the true glycemic effects.

PMID- 22648717
TI  - Oral magnesium supplementation in children with cystic fibrosis improves clinical
      and functional variables: a double-blind, randomized, placebo-controlled
      crossover trial.
AB  - BACKGROUND: Magnesium is one of the most important minerals in the body. Although
      some studies reported that patients with cystic fibrosis (CF) lack magnesium, no
      international study has assessed the importance of oral magnesium supplementation
      in CF patients. OBJECTIVE: We prospectively investigated the long-term effect of
      oral magnesium supplementation on respiratory muscle strength by using
      manuvacuometry and the Shwachman-Kulczycki (SK) score among children and
      adolescents with CF. DESIGN: This double-blind, randomized, placebo-controlled
      crossover study included 44 CF patients (aged 7-19 y; 20 males) who were randomly
      assigned to receive magnesium (n = 22; 300 mg/d) or placebo (n = 22) for 8 wk
      with a 4-wk washout period between trials. All patients were undergoing
      conventional treatment of CF. The experimental protocol included clinical
      evaluation, assessment of urinary concentration of magnesium, and manuvacuometric
      measurements [maximal inspiratory pressure (MIP) and maximal expiratory pressure
      (MEP)]. MIP was the primary outcome. RESULTS: Urinary magnesium increased after
      the administration of magnesium (change: 36.38 mg/d after magnesium compared with
      0.72 mg/d after placebo; P < 0.001). Moreover, MIP and MEP significantly improved
      only after magnesium administration (change in MIP: 11% predicted after magnesium
      compared with 0.5% predicted after placebo; change in MEP: 11.9% predicted after
      magnesium compared with 0.8% predicted after placebo; P < 0.001 for both).
      Magnesium administration had a beneficial effect on clinical variables assessed
      by the SK score (change: 4.48 points after magnesium compared with -1.30 points
      after placebo; P < 0.001). CONCLUSION: Oral magnesium supplementation helped
      improve both the SK score and respiratory muscle strength in pediatric patients
      with CF.

PMID- 22648718
TI  - Serum 1,25-dihydroxyvitamin D and calcium intake affect rates of bone calcium
      deposition during pregnancy and the early postpartum period.
AB  - BACKGROUND: Factors affecting bone calcium deposition across pregnancy and
      lactation are not well characterized. OBJECTIVE: The impact of maternal age,
      calcium intake, race-ethnicity, and vitamin D status on the rate of bone calcium
      deposition (VO+) was assessed across pregnancy and lactation. DESIGN: Stable
      calcium isotopes were given to 46 women at pre- or early pregnancy (trimester 1),
      late pregnancy (trimester 3), and 3-10 wk postpartum. Three cohorts were
      included: 23 adolescents from Baltimore (MD), aged 16.5 +/- 1.4 y (mean +/- SD;
      Baltimore cohort); 13 adults from California, aged 29.5 +/- 2.6 y (California
      cohort); and 10 adults from Brazil, aged 30.4 +/- 4.0 y (Brazil cohort). The
      total exchangeable calcium pool, VO+, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin
      D [1,25(OH)2D], parathyroid hormone, and calcium intake were evaluated. RESULTS:
      At trimester 3, inverse associations between 1,25(OH)2D and VO+ were evident in
      the Baltimore (P = 0.059) and Brazil (P = 0.008) cohorts and in the whole group
      (P = 0.029); calcium intake was not a significant determinant of VO+ in any group
      during pregnancy. At postpartum, a significant positive association was evident
      between VO+ and calcium intake (P <= 0.002) and between VO+ and African ethnicity
      (P <= 0.004) in the whole group and within the Baltimore and Brazil cohorts.
      CONCLUSIONS: Elevated 1,25(OH)2D was associated with decreased rates of bone
      calcium deposition during late pregnancy, a finding that was particularly evident
      in pregnant adolescents and adult women with low calcium intakes. Higher dietary
      calcium intakes and African ethnicity were associated with elevated rates of bone
      calcium deposition in the postpartum period.

PMID- 22648719
TI  - Do children eat less at meals when allowed to serve themselves?
AB  - BACKGROUND: The effect of self-serving on young children's energy intake is not
      well understood. OBJECTIVE: The objective was to examine individual differences
      in the effects of plated and self-served entree portions on children's energy
      intake. DESIGN: Two within-subjects experiments were used to examine ad libitum
      intake at meals in 63 children aged 3-5 y when 400 g of a pasta entree was either
      plated or available for children to self-serve. Child age, sex, BMI, and
      responsiveness to increasing portion size (defined as individual slope estimates
      relating ad libitum intake of the entree across a range of entree portions) were
      evaluated as predictors of self-served portions. RESULTS: Children's entree and
      meal intakes did not differ between the self-served and plated conditions for the
      total sample or by child weight status. However, larger self-served entree
      portions were associated with greater entree and meal intakes. Children who
      served themselves larger entree portions tended to be overweight and more
      responsive to portion size (ie, greater increases in entree intake as plated
      portion size increased). Last, self-served portion predicted both entree and meal
      intake over and above BMI z score and responsiveness to portion. CONCLUSIONS:
      Contrary to our hypothesis, relative to plated portions, allowing children to
      self-serve the entree portion did not reduce energy intake. Children who were
      more responsive to portion-size effects were likely to self-serve and eat larger
      entree portions. Self-serving is not a one-size-fits-all approach; some children
      may need guidance and rules to learn how to self-select appropriate portion
      sizes.

PMID- 22648720
TI  - Comparison of complementary feeding strategies to meet zinc requirements of older
      breastfed infants.
AB  - BACKGROUND: The low zinc intake from human milk at ~6 mo of age predicts the
      dependence on complementary foods (CF) to meet the zinc requirements of older
      breastfed-only infants. OBJECTIVE: The objective of this study was to compare
      major variables of zinc homeostasis and zinc status in 9-mo-old breastfed infants
      who were randomly assigned to different complementary food regimens. DESIGN:
      Forty-five exclusively breastfed 5-mo-old infants were randomly assigned to
      receive commercially available pureed meats, iron-and-zinc-fortified infant
      cereal (IZFC), or whole-grain, iron-only-fortified infant cereal (IFC) as the
      first and primary CF until completion of zinc metabolic studies between 9 and 10
      mo of age. A zinc stable-isotope methodology was used to measure the fractional
      absorption of zinc (FAZ) in human milk and CF by dual-isotope ratios in urine.
      Calculated variables included the dietary intake from duplicate diets and 4-d
      test weighing, the total absorbed zinc (TAZ) from FAZ * diet zinc, and the
      exchangeable zinc pool size (EZP) from isotope enrichment in urine. RESULTS: Mean
      daily zinc intakes were significantly greater for the meat and IZFC groups than
      for the IFC group (P < 0.001); only intakes in meat and IZFC groups met estimated
      average requirements. Mean (+/-SEM) TAZ amounts were 0.80 +/- 0.08, 0.71 +/-
      0.09, and 0.52 +/- 0.05 mg/d for the meat, IZFC, and IFC groups, respectively (P
      = 0.027). Zinc from human milk contributed <25% of TAZ for all groups. The EZP
      correlated with both zinc intake (r = 0.43, P < 0.01) and TAZ (r = 0.54, P <
      0.001). CONCLUSION: Zinc requirements for older breastfed-only infants are
      unlikely to be met without the regular consumption of either meats or zinc
      fortified foods.

PMID- 22648721
TI  - Maternal periconceptional folic acid intake and risk of autism spectrum disorders
      and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and
      Environment) case-control study.
AB  - BACKGROUND: Periconceptional folate is essential for proper neurodevelopment.
      OBJECTIVE: Maternal folic acid intake was examined in relation to the risk of
      autism spectrum disorder (ASD) and developmental delay (DD). DESIGN: Families
      enrolled in the CHARGE (CHildhood Autism Risks from Genetics and Environment)
      Study from 2003 to 2009 were included if their child had a diagnosis of ASD (n =
      429), DD (n = 130), or typical development (TD; n = 278) confirmed at the
      University of California Davis Medical Investigation of Neurodevelopmental
      Disorders Institute by using standardized clinical assessments. Average daily
      folic acid was quantified for each mother on the basis of dose, brands, and
      intake frequency of vitamins, supplements, and breakfast cereals reported through
      structured telephone interviews. RESULTS: Mean (+/-SEM) folic acid intake was
      significantly greater for mothers of TD children than for mothers of children
      with ASD in the first month of pregnancy (P1; 779.0 +/- 36.1 and 655.0 +/- 28.7
      MUg, respectively; P < 0.01). A mean daily folic acid intake of >=600 MUg
      (compared with <600 MUg) during P1 was associated with reduced ASD risk (adjusted
      OR: 0.62; 95% CI: 0.42, 0.92; P = 0.02), and risk estimates decreased with
      increased folic acid (P-trend = 0.001). The association between folic acid and
      reduced ASD risk was strongest for mothers and children with MTHFR 677 C>T
      variant genotypes. A trend toward an association between lower maternal folic
      acid intake during the 3 mo before pregnancy and DD was observed, but not after
      adjustment for confounders. CONCLUSIONS: Periconceptional folic acid may reduce
      ASD risk in those with inefficient folate metabolism. The replication of these
      findings and investigations of mechanisms involved are warranted.

PMID- 22648722
TI  - Supplementation with B vitamins or n-3 fatty acids and depressive symptoms in
      cardiovascular disease survivors: ancillary findings from the SUpplementation
      with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acids (SU.FOL.OM3)
      randomized trial.
AB  - BACKGROUND: Dietary factors might affect depressive symptoms. OBJECTIVE: In
      secondary data analyses, we examined effects of supplementation with B vitamins
      or n-3 (omega-3) fatty acids on depressive symptoms in cardiovascular disease
      survivors. DESIGN: The SUpplementation with FOLate, vitamins B-6 and B-12 and/or
      OMega-3 fatty acids (SU.FOL.OM3) trial was a secondary prevention trial (2003
      2009; n = 2501) in which individuals aged 45-80 y were randomly assigned, by
      using a 2 * 2 factorial design, to receive 0.56 mg 5-methyl-tetrahydrofolate and
      vitamins B-6 (3 mg) and B-12 (0.02 mg); EPA and DHA (600 mg) in a 2:1 ratio; B
      vitamins and n-3 fatty acids; or a placebo. Depressive symptoms were evaluated at
      years 3 and 5 with the 30-item Geriatric Depression Scale (GDS). Overall and sex
      specific ORs and 95% CIs were estimated in 2000 participants by using factorial
      logistic regression. RESULTS: After a median of 4.7 y of supplementation, there
      was no association between allocation to receive B vitamins and depressive
      symptoms. However, the allocation to receive n-3 fatty acids was positively
      associated with depressive symptoms (GDS >10) in men (adjusted OR: 1.28; 95% CI:
      1.03, 1.61) but not in women. CONCLUSIONS: We showed no beneficial effects of a
      long-term, low-dose supplementation with B vitamins or n-3 fatty acids on
      depressive symptoms in cardiovascular disease survivors. The adverse effects of n
      3 fatty acids in men merit confirmation.

PMID- 22648723
TI  - Differential gene expression in adipose tissue from obese human subjects during
      weight loss and weight maintenance.
AB  - BACKGROUND: Differential gene expression in adipose tissue during diet-induced
      weight loss followed by a weight stability period is poorly characterized.
      Markers of these processes may provide a deeper understanding of underlying
      mechanisms. OBJECTIVE: We aimed to identify differentially expressed genes in
      human adipose tissue during weight loss and weight maintenance after weight loss.
      DESIGN: RNA from subcutaneous abdominal adipose tissue from 9 obese subjects was
      analyzed by using a complementary DNA microarray at baseline after weight loss on
      a low-calorie diet and after weight maintenance. RESULTS: Subjects lost 18.8 +/-
      1.8% of weight and maintained this loss during weight maintenance (1.1 +/- 2.1%;
      range: -9.3 to 10.6%). Most differentially expressed genes exhibited a reciprocal
      regulation and returned to baseline after weight loss (2163 genes) and weight
      maintenance (3175 genes). CETP and ABCG1, both of which participate in the HDL
      mediated reverse cholesterol transport (RCT), were among the most upregulated of
      the 750 genes that were differentially expressed after both processes. Several
      genes involved in inflammation were downregulated. The use of real-time
      polymerase chain reaction confirmed or partially confirmed the previously
      implicated genes TNMD and MMP9 (both downregulated), PNPLA3 (upregulated), and
      CIDEA and SCD (both reciprocally regulated). CONCLUSIONS: The beneficial effects
      of weight loss should be investigated after long-term weight maintenance. The
      processes of weight loss and weight maintenance should be viewed as biologically
      distinct. CETP and ABCG1 may be important mediators of these effects through HDL
      mediated RCT.

PMID- 22648724
TI  - Cross-sectional study of conjugated linoleic acid in adipose tissue and risk of
      diabetes.
AB  - BACKGROUND: Some experimental studies on conjugated linoleic acid (CLA) and
      insulin regulation suggested that CLA could be associated with risk of diabetes,
      but epidemiologic studies are lacking. OBJECTIVE: The aim of the study was to
      test whether the amount of CLA in adipose tissue is associated with risk of
      diabetes. DESIGN: A cross-sectional design was used to test the study hypothesis
      in 232 adults with diabetes and 1512 adults without diabetes who lived in Costa
      Rica. The cis-9, trans-11 and trans-10, cis-12 CLA isomers in adipose tissue and
      48 other fatty acids were assessed by using gas chromatography. Prevalence ratios
      (PRs) and 95% CIs were estimated by using Poisson regression adjusted for
      potential confounders. RESULTS: The mean (+/-SD) percentage of total fatty acids
      of CLA for the cis-9, trans-11 isomer in adipose tissue was 0.57 +/- 0.18% in
      adults without diabetes and 0.53 +/- 0.17% in adults with diabetes (P = 0.0078).
      The trans-10, cis-12 CLA isomer was not detected in adipose tissue. The cis-9,
      trans-11 CLA isomer was associated with a lower risk of diabetes. In comparison
      with the first quintile, the PR (95% CI) for the fifth quintile was 0.48 (0.31,
      0.76) (P-trend = 0.0005) in the basic and 0.46 (0.29, 0.72) (P-trend = 0.0002) in
      the multivariable model. Additional adjustment for other fatty acids in adipose
      tissue including trans-9 16:1, which is a fatty acid that was previously
      associated with diabetes, did not modify the results. CONCLUSION: The observed
      inverse association between the cis-9, trans-11 CLA in adipose tissue and
      diabetes risk is consistent with the hypothesis that CLA may be involved in
      insulin regulation.

PMID- 22648725
TI  - Olive oil intake and mortality within the Spanish population (EPIC-Spain).
AB  - BACKGROUND: Olive oil consumption is associated with a decreased risk of several
      chronic diseases, in particular cardiovascular disease (CVD). However, data on
      the effects of olive oil on overall mortality are scarce. OBJECTIVE: We evaluated
      the association between olive oil and overall and cause-specific mortality in the
      Spanish population in the European Prospective Investigation into Cancer and
      Nutrition (EPIC-Spain). DESIGN: A total of 40,622 participants (62% female) aged
      29-69 y were recruited from 5 Spanish regions in 1992-1996. The association
      between olive oil (analyzed as a categorical and continuous variable) and overall
      and cause-specific mortality (CVD, cancer, and other causes) was analyzed by
      using Cox proportional hazards regression models adjusted for potential
      confounders. RESULTS: A total of 1915 deaths were reported during 13.4 y of
      follow-up: 416 CVD deaths, 956 cancer deaths, and 417 deaths from other causes
      (for 126 deaths the cause was not available). In comparison with nonconsumers,
      the highest quartile of olive oil consumption was associated with a 26% (95% CI:
      13%, 36%) reduction in risk of overall mortality and a 44% (95% CI: 21%, 60%)
      reduction in CVD mortality. For each increase in olive oil of 10 g . 2000 kcal-1
      . d-1, there was a 7% (95% CI: 3%, 10%) decreased risk of overall mortality and a
      13% (95% CI: 6%, 20%) decreased risk of CVD mortality. No significant association
      was observed between olive oil and cancer mortality. CONCLUSIONS: Olive oil was
      associated with a decreased risk of overall mortality and an important reduction
      in CVD mortality in this large Mediterranean cohort. This provides further
      evidence on the beneficial effects of one of the key Mediterranean dietary
      components.

PMID- 22648726
TI  - Fiber intake and total and cause-specific mortality in the European Prospective
      Investigation into Cancer and Nutrition cohort.
AB  - BACKGROUND: Previous studies have shown that high fiber intake is associated with
      lower mortality. However, little is known about the association of dietary fiber
      with specific causes of death other than cardiovascular disease (CVD). OBJECTIVE:
      The aim of this study was to assess the relation between fiber intake, mortality,
      and cause-specific mortality in a large European prospective study of 452,717 men
      and women. DESIGN: HRs and 95% CIs were estimated by using Cox proportional
      hazards models, stratified by age, sex, and center and adjusted for education,
      smoking, alcohol consumption, BMI, physical activity, total energy intake, and,
      in women, ever use of menopausal hormone therapy. RESULTS: During a mean follow
      up of 12.7 y, a total of 23,582 deaths were recorded. Fiber intake was inversely
      associated with total mortality (HR(per 10-g/d increase): 0.90; 95% CI: 0.88,
      0.92); with mortality from circulatory (HR(per 10-g/d increase): 0.90 and 0.88
      for men and women, respectively), digestive (HR: 0.61 and 0.64), respiratory (HR:
      0.77 and 0.62), and non-CVD noncancer inflammatory (HR: 0.85 and 0.80) diseases;
      and with smoking-related cancers (HR: 0.86 and 0.89) but not with non-smoking
      related cancers (HR: 1.05 and 0.97). The associations were more evident for fiber
      from cereals and vegetables than from fruit. The associations were similar across
      BMI and physical activity categories but were stronger in smokers and
      participants who consumed >18 g alcohol/d. CONCLUSIONS: Higher fiber intake is
      associated with lower mortality, particularly from circulatory, digestive, and
      non-CVD noncancer inflammatory diseases. Our results support current
      recommendations of high dietary fiber intake for health maintenance.

PMID- 22648727
TI  - Vitamin D intake is inversely related to risk of developing metabolic syndrome in
      African American and white men and women over 20 y: the Coronary Artery Risk
      Development in Young Adults study.
AB  - BACKGROUND: Vitamin D intake may play a key role in the prevention of
      cardiovascular disease. OBJECTIVE: We evaluated associations of dietary and
      supplemental vitamin D intake with the 20-y incidence of metabolic syndrome.
      DESIGN: Data from 4727 black and white young men and women from the Coronary
      Artery Risk Development in Young Adults study were used to examine relations of
      dietary plus supplemental vitamin D intake with the incidence of metabolic
      syndrome (as defined by Adult Treatment Panel, third report, guidelines) and the
      prevalence of its components, including abdominal obesity, elevated blood
      pressure, and high glucose, low HDL, and high triglyceride concentrations.
      RESULTS: The intake of vitamin D from dietary and supplemental sources was
      inversely related to the 20-y cumulative prevalence of abdominal obesity (P =
      0.05) and high glucose (P = 0.02) and low HDL (P = 0.004) concentrations after
      adjustment for age, sex, race, education, center, and energy intake. In
      comparison with the lowest intake quintile (quintile 1), HRs (95% CIs) of
      developing incident metabolic syndrome for quintiles 2-5 of vitamin D intake were
      0.82 (0.67, 1.00), 0.84 (0.68, 1.03), 0.70 (0.56, 0.88), and 0.82 (95% CI: 0.65,
      1.02), respectively (P-trend = 0.03) after adjustment for demographic and
      lifestyle factors. CONCLUSIONS: In young adults, the dietary plus supplemental
      vitamin D intake was inversely related to the development of incident metabolic
      syndrome over 20 y of follow-up. These findings support the recommendations of
      the Dietary Guidelines for Americans to increase intakes of vitamin D-rich foods,
      such as milk and fish.

PMID- 22648728
TI  - Lyase activity of glycogen synthase: Is an elimination/addition mechanism a
      possible reaction pathway for retaining glycosyltransferases?
AB  - Despite the biological relevance of glycosyltrasferases (GTs) and the many
      efforts devoted to this subject, the catalytic mechanism through which a subclass
      of this large family of enzymes, namely those that operate with net retention of
      the anomeric configuration, has not been fully established. Here, we show that in
      the absence of an acceptor, an archetypal retaining GT such as Pyrococcus abyssi
      glycogen synthase (PaGS) reacts with its glucosyl donor substrate, uridine 5'
      diphosphoglucose (UDP-Glc), to produce the scission of the covalent bond between
      the terminal phosphate oxygen of UDP and the sugar ring. X-ray diffraction
      analysis of the PaGS/UDP-Glc complex shows no electronic density attributable to
      the UDP moiety, but establishes the presence in the active site of the enzyme of
      a glucose-like derivative that lacks the exocyclic oxygen attached to the
      anomeric carbon. Chemical derivatization followed by gas chromatography/mass
      spectrometry of the isolated glucose-like species allowed us to identify the
      molecule found in the catalytic site of PaGS as 1,5-anhydro-D-arabino-hex-1
      enitol (AA) or its tautomeric form, 1,5-anhydro-D-fructose. These findings are
      consistent with a stepwise S(N) i-like mechanism as the modus operandi of
      retaining GTs, a mechanism that involves the discrete existence of an
      oxocarbenium intermediate. Even in the absence of a glucosyl acceptor, glycogen
      synthase (GS) promotes the formation of the cationic intermediate, which, by
      eliminating the proton of the adjacent C2 carbon atom, yields AA. Alternatively,
      these observations could be interpreted assuming that AA is a true intermediate
      in the reaction pathway of GS and that this enzyme operates through an
      elimination/addition mechanism.

PMID- 22648729
TI  - Relationship between oral health, diabetes management and sleep apnea.
AB  - OBJECTIVES: The aim of this study was to assess the relationship between tooth
      loss, toothbrushing behaviour, diabetes type 2 (DM2), obesity and sleep apnea
      among diabetics. MATERIAL AND METHODS: DM2 patients (n = 165) in Istanbul,
      Turkey, were randomly selected from the outpatient clinics of two hospitals.
      Baseline clinical measurements (HbA1c, fasting blood glucose, high-density
      lipoprotein (HDL), low-density lipoprotein (LDL), body mass index (BMI), body-fat
      proportion, tooth loss) and self-administered questionnaires (toothbrushing,
      gingival bleeding, sleep apnea) provided data for factor and principal component
      analysis with Varimax rotation. Univariate statistics and chi-square tests were
      derived. RESULTS: Mean maxillary tooth loss (4.49 +/- 3.69 teeth) was higher than
      in the mandible (3.43 +/- 3.12 teeth, p< 0.001). Favourable HDL was measured
      among most patients (77%); other favourable clinical measures occurred only in a
      minority of participants (HbA1c, 28%; fasting blood glucose, 17%; LDL, 30%).
      Twice daily toothbrushing was reported by 33% (17%) for healthy BMI; 37% when
      healthy body-fat proportions. There was risk of sleep apnea in 37 %. The higher
      number of lost teeth in the maxilla was linked with obesity and sleep apnea. Non
      daily toothbrushers were more likely to have high LDL and low HDL cholesterol and
      a higher risk of sleep apnea. When "at least occasionally" bleeding on
      toothbrushing occurred, higher HbA1c levels and sleep apnea were more likely.
      CONCLUSION: Oral care with early diagnosis and monitoring of glycaemic level can
      help prevent complications of DM2. CLINICAL RELEVANCE: Dentists may play a key
      role in better managing and diagnosing sleep apnea early by referring the
      patients with severe tooth loss and periodontal disease for general medical
      examination.

PMID- 22648730
TI  - Angiomatosis of the paranasal sinuses.
AB  - Angiomatosis is a rare benign lesion of the head and neck that can be mistaken
      for either a vascular malformation or malignant disease as a result of its
      infiltrative nature. The recurrence rate of angiomatosis requiring surgery is
      reported to be >90%, and as such the otolaryngologist treating this condition
      should endeavor to remove all disease during the first operation while
      maintaining a high level of suspicion for recurrence during postoperative
      surveillance. This case represents the first report of angiomatosis involving the
      nose and/or paranasal sinuses, and extends the differential diagnosis of
      sinonasal tumors, of which the otolaryngologist must be aware. A description of
      the surgical care and postoperative surveillance recommendations is detailed in
      this first reported case of angiomatosis of the paranasal sinuses.

PMID- 22648731
TI  - Effect of supplementation with an 80:20 cis9,trans11 conjugated linoleic acid
      blend on the human platelet proteome.
AB  - SCOPE: The dietary fatty acid cis9,trans11 conjugated linoleic acid (cis9,trans11
      CLA) has been shown to modify the function of endothelial cells, monocytes, and
      platelets, all of which are involved in the development of atherosclerosis.
      Potential mechanisms for the platelet effects have not been assessed previously.
      In this study, we assessed how supplementation of the diet with an 80:20
      cis9,trans11 CLA blend affects the platelet proteome. METHODS AND RESULTS: In a
      double-blind, randomized, placebo-controlled, parallel-group trial, 40 overweight
      but apparently healthy adults received either 4 g per day of cis9,trans11 CLA
      enriched oil or placebo oil, consisting of palm oil and soybean oil, for 3
      months. Total platelet proteins were extracted from washed platelets, separated
      using two-dimensional gel electrophoresis and differentially regulated protein
      spots were identified by LC-ESI-MS/MS. Supplementation with the CLA blend,
      compared with placebo, resulted in significant alterations in levels of 46 spots
      (p < 0.05), of which 40 were identified. Network analysis revealed that the
      majority of these proteins participate in regulation of the cytoskeleton and
      platelet structure, as well as receptor action, signaling, and focal adhesion.
      CONCLUSION: The platelet proteomics approach revealed novel insights into
      regulation of cellular biomarkers of atherogenic and thrombotic pathways by an
      80:20 cis9,trans11 CLA blend.

PMID- 22648732
TI  - Examination of ancestral informative markers and self-reported race with tumor
      characteristics of breast cancer among Black and White women.
AB  - African American (AA) women have a higher mortality from breast cancer (BC)
      compared to European American (EA) women. This may be due to the higher
      proportion of AA women with tumors that are diagnosed at more advanced stages and
      are characterized as being estrogen receptor negative (ER-)/progesterone receptor
      negative (PR-). Our study sought to determine whether self-reported race and
      percent African ancestry were associated with BC tumor characteristics. In a
      multi-center, population-based case-control study of BC, we determined percent
      African ancestry using ancestry informative markers (AIM) among women self
      reporting race as AA or Black. BC tumor characteristics were associated with self
      reported race (including a 30 % reduction in ER+/PR+ tumors [95 % confidence
      interval [CI]: 0.6-0.9] and a 1.5-fold increased risk of high grade [95 % CI: 1.2
      1.9] for AA women compared to EA women). AIMs among AA women were not associated
      with BC tumor characteristics (AA women with >=95 % versus <80 % African
      ancestry, odds ratio [OR] = 1.0 for ER+/PR+ [95 % CI: 0.6-1.8] and OR = 0.9 for
      high-grade tumors [95 % CI: 0.6-1.4]). Similar findings were observed for BC
      stage. While BC subtypes were associated with self-reported race, BC subtypes
      were not associated with percent African ancestry. These study results suggest
      that subtle differences in percent African ancestry are less important than the
      overall presence of African ancestry in relation to BC tumor characteristics.

PMID- 22648733
TI  - Changes in proteolytic enzymes mRNAs and proteins relevant for meat quality
      during myogenesis and hypoxia of primary bovine satellite cells.
AB  - The current study was conducted to evaluate the functions of MU-calpain (CAPN1),
      calpastatin, HSPs (heat shock proteins), and caspases during myogenesis and cell
      death induced by sodium azide (NaN(3)) hypoxia. The cell samples were divided
      into three groups: satellite cells formed at confluent monolayer (stage 1), stage
      1 cells fusion into myotubes on d eight post-differentiation (stage 2), and stage
      2 cells treated with 1 mM NaN(3) for 24 h (stage 3). Real-time RT-PCR showed that
      stage 2 cells had increased CAPN1, calpastatin, caspase 7, and CARD9 (Caspase
      activation and recruitment domain 9) mRNA expressions compared to stage 1 cells
      (*p < 0.05). By Western blotting caspase 3, caspase 7, caspase 8, and caspase 9
      protein levels increased in cells at stage 2 compared to cells at stage 1 (*p <
      0.05). Real-time RT-PCR showed that stage 3 cells had increased CAPN1,
      calpastatin, caspase 7, HSP70 (70 kDA heat shock proteins), and HSP90 (90 kDA
      heat shock proteins-alpha) and decreased CARD9 mRNA expression compared to stage
      2 cells (*p < 0.05). Stage 3 samples had increase caspase 7 and caspase 12
      activities compared to stage 2 samples, and by Western blotting protein levels of
      both HSP70 and HSP90 expressions, increased significantly under hypoxia condition
      (*p < 0.05). Here, we conclude that CAPN1, calpastatin, caspase 3, caspase 7,
      caspase 8, and CARD9 have important roles for satellite cell myogenesis; and that
      caspase 7, 12, HSP70, and HSP90 are involved in the process of apoptotic cell
      death under hypoxia conditions and we speculate that these proteins may be
      involved in early postmortem proteolysis and meat tenderization.

PMID- 22648734
TI  - Edaravone ameliorates oxidative stress associated cholinergic dysfunction and
      limits apoptotic response following focal cerebral ischemia in rat.
AB  - Stroke is a life-threatening disease with major cause of mortality and morbidity
      worldwide. The neuronal damage following cerebral ischemia is a serious risk to
      stroke patients. Oxidative stress and apoptotic damage play an important role in
      cerebral ischemic pathogenesis and may represent a target for treatment. The
      objective of this study was to test the hypothesis that administration of
      edaravone (Edv) maintains antioxidant status in brain, improves the cholinergic
      dysfunction and suppresses the progression of apoptosis response in rat. To test
      this hypothesis, male Wistar rats were subjected to middle cerebral artery
      occlusion (MCAO) of 2 h followed by reperfusion for 22 h. Edv was administered
      (10 mg/kg bwt) intraperitoneally 30 min before the onset of ischemia and 1 h
      after reperfusion. After reperfusion, rats were tested for neurobehavioral
      activities and were sacrificed for the infarct volume, estimation of oxidative
      damage markers. Edv treatment significantly reduced ischemic lesion volume,
      improved neurological deficits, contended oxidative loads, and suppressed
      apoptotic damage. In conclusion, treatment with Edv ameliorated the neurological
      and histological outcomes with elevated endogenous anti-oxidants status as well
      as reduced induction of apoptotic responses in MCA occluded rat. We theorized
      that Edv is among the pharmacological agents that reduce free radicals and its
      associated cholinergic dysfunction and apoptotic damage and have been found to
      limit the extent of brain damage following stroke.

PMID- 22648735
TI  - Exercise preconditioning provides early cardioprotection against exhaustive
      exercise in rats: potential involvement of protein kinase C delta translocation.
AB  - The objective of this study was to investigate the early cardioprotective effect
      of exercise preconditioning (EP) on the exhaustive exercise-induced myocardial
      injury in rats and the role of protein kinase C delta isoform (PKCdelta) in EP.
      Rats were subjected to run on the treadmill for four periods of 10 min each at 30
      m/min with intervening periods of rest of 10 min as an EP protocol. The
      exhaustive exercise was performed 0.5 h after EP. PKC inhibitor chelerythrine
      (CHE) was injected before EP. Our results showed that EP markedly attenuated the
      exhaustive exercise-induced myocardial ischemia/hypoxia, ultrastructural damage,
      high serum cTnI, and NT-proBNP levels. CHE injection before EP did not abolish
      the protection of EP. Both exhaustive exercise and EP produced a significant
      increase in PKCdelta and p-PKCdelta(Thr507) protein levels in cardiomyocytes.
      However, the immunostaining of p-PKCdelta(Thr507) in EP cardiomyocytes was
      primarily localized to intercalated disks and nuclei while the exhaustive
      exercise-induced high level p-PKCdelta(Thr507) was mainly distributed in the
      cytoplasm. Moreover, the high PKCdelta and p-PKCdelta(Thr507) levels in
      exhaustive exercise were significantly down-regulated by EP. CHE did not
      attenuate the expressions of PKCdelta and p-PKCdelta(Thr507). These results
      indicate that an appropriate activation and translocation of PKCdelta may
      represent a mechanism whereby EP can exert an early cardioprotection against
      exhaustive exercise-induced myocardial injury.

PMID- 22648737
TI  - Cancer cachexia is associated with a decrease in skeletal muscle mitochondrial
      oxidative capacities without alteration of ATP production efficiency.
AB  - BACKGROUND: Cancer cachexia is a complex syndrome related to a negative energy
      balance resulting in muscle wasting. Implication of muscle mitochondrial
      bioenergetics alterations during cancer cachexia was suggested. Therefore, the
      aim of this study was to explore the efficiency of oxidative phosphorylation in
      skeletal muscle mitochondria in a preclinical model of cancer cachexia. METHODS:
      Berlin-Druckrey IX rats with peritoneal carcinosis (PC) were used as a model of
      cancer cachexia with healthy pair-fed rats (PF) as control. Hindlimb muscle
      morphology and fibre type composition were analysed in parallel with ubiquitin
      ligases and UCP gene expression. Oxidative phosphorylation was investigated in
      isolated muscle mitochondria by measuring oxygen consumption and ATP synthesis
      rate. RESULTS: PC rats underwent significant muscle wasting affecting fast
      glycolytic muscles due to a reduction in fibre cross-sectional area. MuRF1 and
      MAFbx gene expression were significantly increased (9- and 3.5-fold,
      respectively) in the muscle of PC compared to PF rats. Oxygen consumption in non
      phosphorylating state and the ATP/O were similar in both groups. Muscle UCP2 gene
      was overexpressed in PC rats. State III and the uncoupled state were
      significantly lower in muscle mitochondria from PC rats with a parallel reduction
      in complex IV activity (-30 %). CONCLUSION: This study demonstrated that there
      was neither alteration in ATP synthesis efficiency nor mitochondrial uncoupling
      in skeletal muscle of cachectic rats despite UCP2 gene overexpression. Muscle
      mitochondrial oxidative capacities were reduced due to a decrease in complex IV
      activity. This mitochondrial bioenergetics alteration could participate to
      insulin resistance, lipid droplet accumulation and lactate production.

PMID- 22648736
TI  - Consilience in sarcopenia of cirrhosis.
AB  - Cirrhosis is the consequence of progression of many forms of necro-inflammatory
      disorders of the liver with hepatic fibrosis, hepatocellular dysfunction, and
      vascular remodeling. Reversing the primary hepatic disorder, liver
      transplantation, and controlling the complications are the major management
      goals. Since the former options are not available to the majority of cirrhotics,
      treating complications remains the mainstay of therapy. Sarcopenia and/or
      cachexia is the most common complication and adversely affects survival, quality
      of life, development of other complications of cirrhosis, and outcome after liver
      transplantation. With the increase in number of cirrhotic patients with hepatitis
      C and nonalcoholic fatty liver disease, the number of patients waiting for a
      liver transplantation is likely to continue to increase above the currently
      estimated 72.3/100,000 population. One of the critical clinical questions is to
      determine if we can treat sarcopenia of cirrhosis without transplantation. No
      effective therapies exist to treat sarcopenia because the mechanism(s) of
      sarcopenia in cirrhosis is as yet unknown. The reasons for this include the
      predominantly descriptive studies to date and the advances in our understanding
      of skeletal muscle biology and molecular regulation of atrophy and hypertrophy
      not being translated into the clinical practice of hepatology. Satellite cell
      biology, muscle autophagy and apoptosis, and molecular signaling abnormalities in
      the skeletal muscle of cirrhotics are also not known. Aging of the cirrhotic and
      transplanted population, use of mTOR inhibitors, and the lack of definitive
      outcome measures to define sarcopenia and cachexia in this population add to the
      difficulty in increasing our understanding of hepatic sarcopenia/cachexia and
      developing treatment options. Recent data on the role of myostatin, AMP kinase,
      impaired mTOR signaling resulting in anabolic resistance in animal models, and
      the rapidly developing field of nutriceuticals as signaling molecules need to be
      evaluated in human cirrhotics. Finally, the benefits of exercise reported in
      other disease states with sarcopenia may not be safe in cirrhotics due to the
      risk of gastrointestinal variceal bleeding due to an increase in portal pressure.
      This article focuses on the problems facing both muscle biologists and
      hepatologists in developing a comprehensive approach to sarcopenia in cirrhosis.

PMID- 22648738
TI  - Effect of colon cancer and surgical resection on skeletal muscle mitochondrial
      enzyme activity in colon cancer patients: a pilot study.
AB  - BACKGROUND: Colon cancer (CC) patients commonly suffer declines in muscle mass
      and aerobic function. We hypothesised that CC would be associated with reduced
      muscle mass and mitochondrial enzyme activity and that curative resection would
      exacerbate these changes. METHODS: We followed age-matched healthy controls and
      CC patients without distant metastasis on radiological imaging before and 6 weeks
      after hemi-colectomy surgery. Body composition was analysed using dual energy X
      ray absorptiometry. Mitochondrial enzyme activity and protein concentrations were
      analysed in vastus lateralis muscle biopsies. RESULTS: In pre-surgery, there were
      no differences in lean mass between CC patients and age-matched controls (46.1 +
      32.5 vs. 46.1 + 37.3 kg). Post-resection lean mass was reduced in CC patients
      (43.8 + 30.3 kg, P < 0.01). When comparing markers of mitochondrial function, the
      following were observed: pyruvate dehydrogenase (PDH) activity was lower in CC
      patients pre-surgery (P < 0.001) but normalized post-resection and cytochrome c
      oxidase and pyruvate dehydrogenase E2 subunit protein expression were lower in CC
      patients pre-surgery and not restored to control values post-resection (P <
      0.001). Nuclear factor kappa-B, an inflammatory marker, was higher in CC patients
      pre-surgery compared to controls (P < 0.01), returning to control levels post
      resection. CONCLUSION: Muscle mass was affected by surgery rather than cancer per
      se. PDH activity was however lower in cancer patients, suggesting that muscle
      mass and mitochondrial enzyme activity are not inextricably linked. This
      reduction in mitochondrial enzyme activity may well contribute to the significant
      risks of major surgery to which CC patients are exposed.

PMID- 22648739
TI  - Predicting survival in cancer patients: the role of cachexia and hormonal,
      nutritional and inflammatory markers.
AB  - BACKGROUND: Cancer can lead to weight loss, anorexia, and poor nutritional
      status, which are associated with decreased survival in cancer patients. METHODS:
      Male cancer patients (n = 136) were followed for a mean time of 4.5 years.
      Variables were obtained at baseline: cancer stage, albumin, hemoglobin, tumor
      necrosis factor alpha (TNF-alpha), interleukin (IL)-6, bioavailable testosterone,
      appetite questionnaire, and weight change from baseline to 18 months. Primary
      statistical tests included Kaplan-Meier survival analysis and Cox proportional
      hazard regression (PHREG). RESULTS: Univariate PHREG showed that cancer stage,
      albumin, hemoglobin, TNF-alpha, IL-6, and weight change were each significantly
      associated with mortality risk (P < 0.05), but bioavailable testosterone was not.
      Multivariate PHREG analysis established that weight change and albumin were
      jointly statistically significant even after adjusting for stage. CONCLUSION: In
      this sample of male oncology patients, cancer stage, serum albumin, and weight
      loss predicted survival. High levels of inflammatory markers and hemoglobin are
      associated with increased mortality, but do not significantly improve the ability
      to predict survival above and beyond cancer stage, albumin, and weight loss.

PMID- 22648740
TI  - Group sparse reconstruction using intensity-based clustering.
AB  - Compressed sensing has been of great interest to speed up the acquisition of MR
      images. The k-t group sparse (k-t GS) method has recently been introduced for
      dynamic MR images to exploit not just the sparsity, as in compressed sensing, but
      also the spatial group structure in the sparse representation. k-t GS achieves
      higher acceleration factors compared to the conventional compressed sensing
      method. However, it assumes a spatial structure in the sparse representation and
      it requires a time consuming hard-thresholding reconstruction scheme. In this
      work, we propose to modify k-t GS by incorporating prior information about the
      sorted intensity of the signal in the sparse representation, for a more general
      and robust group assignment. This approach is referred to as group sparse
      reconstruction using intensity-based clustering. The feasibility of the proposed
      method is demonstrated for static 3D hyperpolarized lung images and applications
      with both dynamic and intensity changes, such as 2D cine and perfusion cardiac
      MRI, with retrospective undersampling. For all reported acceleration factors the
      proposed method outperforms the original compressed sensing method. Improved
      reconstruction over k-t GS method is demonstrated when k-t GS assumptions are not
      satisfied. The proposed method was also applied to cardiac cine images with a
      prospective sevenfold acceleration, outperforming the standard compressed sensing
      reconstruction.

PMID- 22648741
TI  - The use of black and white infrared photography for recording blunt force injury.
AB  - Infrared (IR) wavelengths penetrate skin and can selectively image volumes of
      subsurface blood. Twenty-eight blunt force injuries on nine decedents were
      photographed with color and IR film to compare the ability of each to image the
      injury. Of the 28 injuries, 10 were clinically interpreted as contusions, 4 as
      abrasions, 10 as abraded contusions, and 4 as erythematous discolorations, nos.
      Twenty-four of these injuries were incised to determine the presence and extent
      of subsurface bleeding. It was found that contusion had been clinically missed in
      five cases, three because they were hidden by abrasion and two because they
      appeared only as a mild cutaneous erythema. All five cases were detected by IR
      and verified by incision. Melanin pigmentation contributed to masking of
      contusion in one case and postmortem lividity confounded interpretation of
      contusion in one case. In all 14 injuries featuring abrasion as a component, IR
      de-emphasized or eliminated the visibility of abrasion. A single false negative
      was reported in which a visible contusion, verified by incision, was not seen
      with IR. In comparing injury patterns, color and IR renditions were dissimilar in
      a number of cases reflecting the difference between the manner in which light and
      IR photography imaged the depth and volume of blood within an injury. In summary,
      IR imaging of wounds can discover hidden bruises, verify clinical diagnosis of
      bruises, and augment interpretation of wound patterns.

PMID- 22648742
TI  - Visualization of sigmoidal diverticulosis during gynecological three-dimensional
      ultrasound examination.

PMID- 22648745
TI  - Phase I pharmacokinetic study of chronomodulated dose-intensified combination of
      capecitabine and oxaliplatin (XELOX) in metastatic colorectal cancer.
AB  - PURPOSE: To evaluate the maximum tolerated dose (MTD) and pharmacokinetic profile
      of a chronomodulated, dose-intensified regimen of capecitabine in combination
      with oxaliplatin (XELOX) in metastatic colorectal cancer (mCRC). METHODS:
      Patients (N = 18) with 0 or 1 line of prior chemotherapy received oxaliplatin 100
      mg/m(2) on day 1 from 1400 to 1800 hours with escalating dose levels of
      capecitabine (2,500, 3,000, 3,500, 4,000, 4,500, and 5,000 mg) once daily taken
      at 2400 hours on days 1-5. Each cycle lasted 14 days. RESULTS: The MTD of
      capecitabine was 4,500 mg. Transaminitis and anemia were the commonest non
      hematologic and hematologic toxicities, respectively. Toxicities were generally
      mild, with only five occurrences of grade 3 toxicity and none of grade 4. There
      were no dose-limiting toxicities, defined as specific grade 3 or 4 toxicities
      occurring in the first two cycles of treatment. The objective response rate was
      33.3 %, and median overall survival was 16.3 months (95 % CI: 11.2-18.2 months).
      The maximum plasma concentration (C(max)) and area under plasma concentration
      time curve from time 0 to infinity (AUC([0-infinity])) of the capecitabine
      metabolites in our fixed-dosing chronomodulated regimen were comparable to values
      seen with comparably dose-intense regimens but associated with significantly
      reduced toxicity. CONCLUSIONS: Chronomodulated dose-intensified XELOX facilitates
      delivery of dose-intense treatment in mCRC with a favorable therapeutic index
      that is promising.

PMID- 22648743
TI  - Differential effects of RET and TRKB on axonal branching and survival of
      parasympathetic neurons.
AB  - Interactions between neurons and their targets of innervation influence many
      aspects of neural development. To examine how synaptic activity interacts with
      neurotrophic signaling, we determined the effects of blocking neuromuscular
      transmission on survival and axonal outgrowth of ciliary neurons from the
      embryonic chicken ciliary ganglion. Ciliary neurons undergo a period of cell loss
      due to programmed cell death between embryonic Days (E) 8 and 14 and they
      innervate the striated muscle of the iris. The nicotinic antagonist d
      tubocurarine (dTC) induces an increase in branching measured by counting
      neurofilament-positive voxels (NF-VU) in the iris between E14-17 while reducing
      ciliary neuron survival. Blocking ganglionic transmission with dihyro-beta
      erythroidin and alpha-methyllycacontine does not mimic dTC. At E8, many trophic
      factors stimulate neurite outgrowth and branching of neurons placed in cell
      culture; however, at E13, only GDNF stimulates branching selectively in cultured
      ciliary neurons. The GDNF-induced branching at E13 could be inhibited by BDNF.
      Blocking ret signaling in vivo with a dominant negative (dn)ret decreases
      survival of ciliary and choroid neurons at E14 and prevents dTC induced increases
      in NF-VU in the iris at E17. Blocking TRKB signaling with dn TRKB increases NF-VU
      in the iris at E17 and decreases neuronal survival at E17, but not at E14. Thus,
      RET promotes survival during programmed cell death in the ciliary ganglion and
      contributes to promoting branching when synaptic transmission is blocked while
      TRKB inhibits branching and promotes maintenance of neuronal survival. These
      studies highlight the multifunctional nature of trophic molecule function during
      neuronal development.

PMID- 22648744
TI  - Impact of internal mammary lymph node drainage identified by preoperative
      lymphoscintigraphy on outcomes in patients with stage I to III breast cancer.
AB  - BACKGROUND: Involvement of internal mammary (IM) lymph nodes is associated with a
      poor prognosis for patients with breast cancer. This study examined the effect of
      drainage to IM nodes identified by lymphoscintigraphy on oncologic outcomes.
      METHODS: A prospectively maintained breast cancer patient database at the
      University of Texas MD Anderson Cancer Center was used to identify patients with
      stage I to III breast cancer who underwent preoperative lymphoscintigraphy with
      peritumoral injection of colloid and intraoperative lymphatic mapping from 1996
      to 2005. Medical records were reviewed of 1772 patients who had drainage to any
      lymph node basin on lymphoscintigraphy but who did not undergo IM nodal biopsy.
      Patients with IM drainage, with or without axillary drainage, were compared with
      patients without IM drainage. Local-regional recurrence, distant disease-free
      survival (DDFS), and overall survival were evaluated. RESULTS: We identified IM
      drainage in 334 patients (18.8%). Patients with IM drainage were significantly
      younger, less likely to have upper outer quadrant tumors, and more likely to have
      smaller and medial tumors than patients without IM drainage. Rates of IM
      irradiation did not differ between the 2 groups. The median follow-up time was
      7.4 years. On multivariate analysis, IM drainage was significantly associated
      with a worse DDFS (hazard ratio, 1.6; 95% confidence interval, 1.03-2.6; P = .04)
      but not local-regional recurrence or overall survival. CONCLUSIONS: IM drainage
      on preoperative lymphoscintigraphy was found to be significantly associated with
      worse DDFS. Further study is needed to determine the role of lymphoscintigraphy
      in the personalization of breast cancer staging and therapy.

PMID- 22648746
TI  - Steroid hormone receptors, matrix metalloproteinases, insulin-like growth factor,
      and dystroglycans interactions in prostatic diseases in the elderly men.
AB  - OBJECTIVES: The aim of this study was to evaluate the reactivity of steroid
      hormone receptors (SHRs), dystroglycans (DGs), matrix metalloproteinases (MMPs),
      insulin-like growth factor receptor (IGFR-1), and laminin (Lam) in both prostatic
      stromal and epithelial compartments showing different diseases in elderly men.
      METHODS: Sixty prostatic samples were obtained from 60- to 90-year-old patients
      (mean 63 years) with and without prostatic lesions from Hospital of the School of
      Medicine, State University of Campinas (UNICAMP). The Samples were divided into
      standard (no lesions); high grade prostatic intraepithelial neoplasia (HGPIN);
      prostatic cancer (PC); and benign prostatic hyperplasia (BPH) groups. The samples
      were submitted to immunohistochemistry and Western blotting analyses. Research
      Ethics Committee of the School of Medicine, University of Campinas/UNICAMP
      (number 0094.0.146.000-08). RESULTS: The results showed increased IGFR-1 and MMPs
      protein levels in the PC and HGPIN groups. Decreased alphaDG and betaDG protein
      levels were verified in the PC and HGPIN groups. Androgen receptor (AR)
      reactivity was similar among all groups. Estrogen receptor alpha (Eralpha)
      immunoreactivity was more intense in the epithelium in the PC and HGPIN groups.
      Estrogen receptor beta (ERbeta) immunoreactivity was weak in the epithelium of
      the HGPIN and PC groups. CONCLUSIONS: To conclude, there was an association among
      IGFR-1, MMPs, and SHRs, indicating IGFR-1 as a target molecule in prostate
      therapy, considering the IGF proliferative properties. Also, the distinct SHRs
      reactivities in the lesions in both prostatic compartments indicated different
      paracrine signals and pointed out the importance of estrogenic pathways in the
      activation of these disorders.

PMID- 22648747
TI  - Arthroscopic ganglionectomy of the foot and ankle.
AB  - PURPOSE: To study the efficacy of arthroscopic ganglionectomy in the management
      of ganglia of the foot and ankle. METHODS: From 2006 to 2010, arthroscopic
      ganglionectomy was performed for 89 ganglia in the foot and ankle of 88 patients.
      Clinical and intra-operative details were reviewed retrospectively. RESULT:
      Ganglion stalk was identified in 6 % of the cases. The overall rate of presence
      of pathology was 26 %. The overall rate of recurrence or residual lesion was 12 %
      with high recurrent rate for extensor tendon ganglia and toe pulp ganglia.
      CONCLUSIONS: Arthroscopic ganglionectomy of the foot and ankle ganglion by either
      internal drainage or complete resection is a feasible approach. Good results can
      be achieved in case of adequate internal drainage of the ganglion to the joints
      or fibrous tendon sheath.

PMID- 22648749
TI  - Perceiving and interacting affordances: a new model of human-affordance
      interactions.
AB  - This article introduces a new affordance framework for humans and human design.
      Based on previous important concepts in product design-affordance, signifier, and
      product semantics, the authors propose three new concepts to illustrate how
      people perceive affordance. According to the model, perceptual probability of
      affordance is the probability that the public can perceive a certain affordance;
      perceptual threshold of affordance is the threshold at which affordance can be
      perceived by a person and changed by perceptual information; and situations, in
      which interactions between affordances and people exist, are crucial influences
      on human-affordance interactions. An illustration of the model and suggestions
      for further research are provided.

PMID- 22648748
TI  - Acromioclavicular and coracoclavicular PDS augmentation for complete AC joint
      dislocation showed insufficient properties in a cadaver model.
AB  - PURPOSE: Optimal surgical treatment of high-grade acromioclavicular joint
      dislocations is still controversially discussed. The purpose of the present
      controlled laboratory study was to evaluate whether a polydioxansulfate
      (PDS((r))) cord augmentation with separate reconstruction of the coracoclavicular
      (CC) ligaments and the acromioclavicular (AC) complex provides sufficient
      vertical stability in a biomechanical cadaver model. METHODS: Twenty-four
      shoulders of fresh-frozen cadaveric specimen were tested. Cyclic loading and load
      to failure protocol was performed in vertical direction on 12 native AC joints
      and repeated after reconstruction. The reconstruction of the coracoclavicular
      ligament was performed using two CC PDS cerclages and an additional AC PDS
      cerclage. RESULTS: In static load testing for vertical force, the native AC joint
      complex measured 590.1 N (+/-95.8 N), elongation 13.4 mm (+/-2.1 mm) and
      stiffness 48.7 N/mm (+/-12.0 N/mm). The mean maximum load to failure in the
      reconstructed joints was 569.9 N (+/-97.9 N), elongation 18.8 mm (+/-4.7 mm) and
      stiffness 37.9 N/mm (+/-8.0 N/mm). During dynamic testing of the reconstructed AC
      joints, all specimens reached the critical elongation of 12.0 mm, defined as
      clinical failure between 200 and 300 N. The mean amount of repetitions at
      clinical failure was 305. A plastic deformation of the reconstructed specimens
      throughout cyclic loading could not be detected. CONCLUSION: The AC joint
      reconstruction with acromioclavicular and coracoclavicular PDS cord cerclages did
      not provide the aspired vertical stability in a cadaver model. LEVEL OF EVIDENCE:
      Basic Science Study.

PMID- 22648750
TI  - Application of multiple shrinkage methods to genomic predictions.
AB  - New challenges have arisen with the development of large marker panels for
      livestock species. Models easily become overparameterized when all available
      markers are included. Solutions have led to the development of shrinkage or
      regularization techniques. The objective of this study was the application and
      comparison of Bayesian LASSO (B-L), thick-tailed (Student-t), and semiparametric
      multiple shrinkage methods. The B-L and Student-t methods were also each analyzed
      within a single shrinkage and a multiple shrinkage framework. Simulated and real
      data were used to evaluate each method's performance. Real data consisted of SNP
      genotypes of 4,069 Holstein sires. Traits included in analysis of real data were
      milk, fat, protein yield, and somatic cell score. The performance of each model
      was compared based on correlations between true and predicted genomic predicted
      transmitting abilities. Model performance was also compared with the performance
      of routinely used methods such as Bayes-A and GBLUP through cross-validation
      techniques. When using simulated data regardless of shrinkage framework,
      shrinkage models outperformed genomic BLUP (GBLUP). The average advantage of
      shrinkage models ranged from 1% to approximately 8% depending on the prior
      specification. When analyzing real data, shrinkage models slightly outperformed
      GBLUP for most traits. Shrinkage models were better able to model traits for
      which 1 or more SNP of large effect have been identified. Overall, results
      suggested a relatively small advantage in multiple shrinkage models. Multiple
      shrinkage methods could represent a useful alternative to current methods of
      prediction; however, their performance in a variety of scenarios needs to be
      investigated further.

PMID- 22648751
TI  - Effects of dietary addition of capsicum extract on intake, water consumption, and
      rumen fermentation of fattening heifers fed a high-concentrate diet.
AB  - Four beef Holstein heifers (BW = 438 +/- 71 kg) fitted with a 1-cm i.d. plastic
      ruminal trocars were used in a 4 * 4 Latin square design to evaluate the effect
      of 3 doses of capsicum extract (CAP) on intake, water consumption, and ruminal
      fermentation in heifers fed a high-concentrate diet. Animals were fed (DM basis)
      10% barley straw and 90% concentrate (32.2% barley grain, 27.9% ground corn, 7.5%
      wheat bran, 10.7% soybean meal, 10.7% soybean hulls, 7.2% corn gluten feed, 3.1%
      mineral-vitamin mix; 16.6% CP, 18.3% NDF). Treatments were no additive (CTR), 125
      (CAP125), 250 (CAP250), and 500 (CAP500) mg/d of capsicum oleoresin standardized
      with 6% of capsaicin and dihydrocapsaicin (XTract 6933, Pancosma, Geneva,
      Switzerland). Each experimental period consisted of 25 d (15 d for adaptation, 5
      d of continuous measurement of DMI, and 3 d for rumen sample collection). Animals
      had ad libitum access to water and feed offered once daily at 0800 h. Data were
      analyzed by the MIXED procedure of SAS. The model included the fixed effects of
      period and treatment, the random effect of heifer, and the residual error. The
      effects were tested for linear and quadratic effects. A linear response was
      observed (CTR, CAP125, CAP250, and CAP500, respectively) for DMI (8.56, 9.84,
      8.68, and 9.40 kg/d; P < 0.04), ruminal pH (6.03, 5.84, 5.96, and 5.86; P < 0.08)
      and total VFA (134.3, 144.8, 140.1, and 142.8 mM; P < 0.08). There was a strong
      correlation between water consumption and DMI (R(2) = 0.98). Dry matter intake in
      the first 2 h after feeding was reduced (P < 0.05) in all CAP treatments compared
      with control. The molar proportion of acetate tended to decrease linearly (from
      59.6 to 55.5 mol/100 mol; P < 0.06), and ammonia N concentration tended to
      increase linearly (from 14.4 to 16.0 mg N/dL; P < 0.08). In contrast, the molar
      proportion of propionate (23.8 mol/100 mol), butyrate (14.2 mol/100 mol), and
      lactate (0.28 mol/100 mol) were not affected by treatments. Results indicate that
      capsicum extract stimulated DMI and modified the pattern of DMI in beef cattle
      fed high concentrate diets.

PMID- 22648752
TI  - Feeding value of dried shredded sugarbeets as a partial replacement for steam
      flaked corn in finishing diets for feedlot cattle.
AB  - Two experiments were conducted to evaluate the comparative feeding value of dried
      shredded sugarbeets (DSSB; 0, 20, and 40% of diet DM) as a replacement for steam
      flaked corn (SFC) in finishing diets for feedlot cattle. In Exp. 1, 60 calf-fed
      Holstein steers (476 +/- 6.3 kg) were used in a 97-d finishing trial.
      Substitution of SFC with DSSB did not affect ADG or DMI (P > 0.20). Increasing
      DSSB decreased gain efficiency (ADG:DMI; linear effect, P = 0.04) and dietary NE
      (linear effect, P = 0.03). Given that SFC has a NE(m) value of 2.38 Mcal/kg, the
      replacement NE(m) and NE(g) values for DSSB were 1.94 and 1.29 Mcal/kg,
      respectively. There were no treatment effects (P > 0.20) on carcass
      characteristics. In Exp. 2, 6 cannulated Holstein steers (205 kg) were used in a
      replicated 3 * 3 Latin square design to evaluate treatment effects on digestion.
      Ruminal digestion of starch, NDF, and feed N were not affected (P > 0.10) by
      DSSB, although ruminal OM digestion tended to increase (linear effect, P < 0.08).
      Replacing SFC with DSSB decreased flow of starch to the small intestine, but it
      increased flow of microbial N (linear effect, P = 0.05). There were no treatment
      effects (P > 0.14) on postruminal digestion of OM, NDF, starch, or feed N or
      total tract digestion of OM, starch, and N. Substitution of DSSB increased
      (linear effect, P = 0.05) total tract NDF digestion and decreased (linear effect,
      P = 0.05) dietary DE (Mcal/kg). Given that SFC has a DE value of 4.19 Mcal/kg,
      the replacement DE value of DSSB was 3.68 Mcal/kg. There were no treatment
      effects (P > 0.12) on ruminal pH or total VFA; however, DSSB decreased propionate
      (linear effect, P = 0.05) and increased acetate (linear effect, P = 0.07),
      butyrate (linear effect, P = 0.05), valerate (linear effect, P = 0.04), and
      estimated methane production (linear effect, P = 0.05). We concluded that DSSB
      may replace SFC in finishing diets at levels of up to 40% without detrimental
      effects on ADG and carcass characteristics. The NE value of DSSB is 82% that of
      SFC (DM basis). Partial replacement of SFC with DSSB alters ruminal VFA patterns,
      increasing estimated methane energy loss and slightly decreasing the efficiency
      of DE utilization.

PMID- 22648753
TI  - Effects of gastrointestinal parasites on parasite burden, rectal temperature, and
      antibody titer responses to vaccination and infectious bovine rhinotracheitis
      virus challenge.
AB  - Thirty-three colostrum-deprived Holstein bull calves (initial BW of 131 +/- 4 kg)
      were used to determine the effect of timing of anthelmintic administration
      relative to vaccination on antibody titer response to vaccine component antigens.
      When calves were at least 3 mo of age, they were sorted randomly into individual
      pens and assigned to 1 of 3 treatment groups, treatments consisted of 1) dewormed
      2 wk before vaccination (DPV), 2) dewormed at the time of vaccination (DV), or 3)
      control, vaccinated but not dewormed (CONT). All calves were inoculated with
      infective larvae of brown stomach worms (Ostertagia ostertagi) and intestinal
      worms (Cooperia spp.) on d 1, 7, 10, 14, and 18 for a total dose of 235,710
      infective larvae per calf. Calves (DPV and DV) were dewormed on d 21 or 35 with a
      10% fenbendazole suspension at 5 mg/kg of BW. On d 35, all calves were vaccinated
      with a modified-live virus respiratory vaccine containing IBRV (infectious bovine
      rhinotracheitis virus), BVDV-1 (bovine viral diarrhea virus genotype 1), BVDV-2
      (BVDV genotype 2), PI-3 (parainfluenza-3), and BRSV (bovine respiratory syncytial
      virus). During the 103-d experiment, weekly fecal egg counts, blood, and rectal
      temperatures were collected and health status was recorded daily. Blood samples
      were obtained weekly to determine serum neutralizing (SN) antibody titers to
      IBRV, BVDV-1, BVDV-2, and PI-3 and cytokine levels for IL-4, IL-6, TNF-alpha
      (tumor necrosis factor-alpha), and IFN-gamma (interferon-gamma). There was a
      tendency (P < 0.09) for CONT calves to have greater IL-4 concentrations. By
      design, control calves had greater (P < 0.01) fecal egg counts during the
      experiment. All calves developed antibody titers to IBRV, BVDV-1, BVDV-2, and PI
      3 by d 15 postvaccination. On d 88, all calves were challenged with IBRV and
      blood samples were obtained on d 88, 89, 90, 93, 95, 98, 99, and 103. All calves
      had increased rectal temperatures during the final 7 d of the IBRV challenge.
      However, the CONT group had greater (P < 0.01) rectal temperatures on each
      sampling day except d 90 compared with the DPV and DV treatments. Therefore,
      deworming before or at vaccination reduced parasite burden and decreased rectal
      temperature increase after an IBRV challenge. Deworming strategy had no effect on
      antibody response to vaccination or IBRV challenge.

PMID- 22648754
TI  - Weaning management of newly received beef calves with or without continuous
      exposure to a persistently infected bovine viral diarrhea virus pen mate: effects
      on health, performance, bovine viral diarrhea virus titers, and peripheral blood
      leukocytes.
AB  - Exposure to animals persistently infected (PI) with bovine viral diarrhea virus
      (BVDV) results in immunomodulation of cohorts that may have health and growth
      consequences; however, effects may differ in low-risk, preconditioned (PC) vs.
      high-risk, auction market (AM) beef cattle. Our objective was to compare health
      and performance of PC or AM management systems with (PI) or without (CON)
      presence of a PI-BVDV pen mate using a 2 * 2 factorial arrangement. Four shipment
      blocks of crossbred PC steers (n = 236) from 3 ranch-origins were weaned,
      dewormed, vaccinated, tested for PI-BVDV, and kept on the ranch for >=42 d.
      Subsequently, PC steers were transported to a stocker receiving unit (RU),
      weighed (251 +/- 2 kg), blood sampled, stratified by d -1 BW, and assigned
      randomly to treatment (PCPI or PCCON) with no additional processing.
      Simultaneously, 4 blocks of crossbred AM calves (n = 292) were assembled from
      regional auction markets and transported to the RU +/- 36 h from PC arrival. The
      AM calves were weighed (245 +/- 1.3 kg), stratified by gender and d -1 BW,
      processed under the same regimen used for PC steers at their origin ranch except
      bull calves were castrated, and then assigned randomly to treatment (AMPI or
      AMCON). Treatment pens (0.45 ha) were arranged spatially such that PI did not
      have fence-line or water source contact with CON. Calves were fed identically and
      followed the same antibiotic treatment protocol. Daily BW gain for the entire 42
      d receiving trial was greater (P < 0.001) for PC (1.2 kg) compared with AM (0.85
      kg). There was an exposure effect (P = 0.002) on ADG from d 28 to 42; CON gained
      1.12 kg vs. 0.90 kg BW for PI cohort. Morbidity was markedly greater (P < 0.001)
      in AM (70%) vs. PC (7%), resulting in (P < 0.001) an antibiotic treatment cost of
      $20.52 and $2.48/animal, respectively. Treatment with a third antibiotic occurred
      more often (P = 0.04) for PI cohort, and the percentage of chronically ill cattle
      was greatest (P = 0.06) for AMPI. Upon arrival, BVDV type 1a, 1b, and 2a titers
      were greater for PC (treatment * day, P < 0.001), and the percentage seropositive
      to BVDV type 1a on d 0 was 100% for PC vs. 23% in AM. Platelets increased
      transiently (P < 0.001) with greater platelets observed in AM (P < 0.001).
      Results indicate that PC calves gain faster and require fewer antibiotic
      treatments during the receiving period. Exposure to PI reduced BW gain from d 28
      to 42, increased the number of calves treated thrice, and increased chronically
      ill cattle for AM.

PMID- 22648755
TI  - Supplementation of dried distillers grains with solubles to beef cows consuming
      low-quality forage during late gestation and early lactation.
AB  - Three experiments were conducted to evaluate supplementation of dried distillers
      grains with solubles (DGS) to spring-calving beef cows (n = 120; 541 kg of
      initial BW; 5.1 initial BCS) consuming low-quality forage during late gestation
      and early lactation. Supplemental treatments included (DM basis) 1) 0.77 kg/d DGS
      (DGSL); 2) 1.54 kg/d DGS (DGSI); 3) 2.31 kg/d DGS (DGSH); 4) 1.54 kg/d of a blend
      of 49% wheat middlings and 51% cottonseed meal (POS); and 5) 0.23 kg/d of a
      cottonseed hull-based pellet (NEG). Feeding rate and CP intake were similar for
      DGSI and POS. In Exp. 1, cows were individually fed 3 d/wk until calving and 4
      d/wk during lactation; total supplementation period was 119 d, encompassing 106 d
      of gestation and 13 d of lactation. Tall-grass prairie hay (5.6% CP, 50% TDN, 73%
      NDF; DM basis) was fed for ad libitum intake throughout the supplementation
      period. Change in cow BW and BCS during gestation was similar for DGSI and POS (
      5.0 kg, P = 0.61 and -0.13, P = 0.25, respectively) and linearly increased with
      increasing DGS level (P < 0.01). Likewise, during the 119-d supplementation
      period, BW and BCS change were similar for DGSI and POS (-72 kg, P = 0.22 and 
      0.60, P = 0.10) and increased linearly with respect to increasing DGS (P < 0.01).
      The percentage of cows exhibiting luteal activity at the beginning of breeding
      season (56%, P = 0.31), AI conception rate (57%, P = 0.62), or pregnancy rate at
      weaning (88%, P = 0.74) were not influenced by supplementation. In Exp. 2, 30
      cows from a separate herd were used to evaluate the effect of DGS on hay intake
      and digestion. Supplementation improved all digestibility measures compared with
      NEG. Hay intake was not influenced by DGS (P > 0.10); digestibility of NDF, ADF,
      CP, and fat linearly increased with increasing DGS. In Exp. 3, milk production
      and composition were determined for cows (n = 16/treatment) of similar days
      postpartum from Exp. 1. Daily milk production was not influenced by
      supplementation (6.3 kg/d, P = 0.25). Milk fat (2.1%) and lactose (5.0%) were not
      different (P > 0.10). Milk protein linearly increased as DGS increased (P < 0.05)
      and was greater for DGSI compared with POS. Similar cow performance was achieved
      when cows were fed DGS at the same rate and level of CP as a traditional
      cottonseed meal-based supplement. Increasing amounts of DGS did not negatively
      influence forage intake or diet digestibility.

PMID- 22648756
TI  - Spoilage characteristics of ground beef with added lactic acid bacteria and
      rosemary oleoresin packaged in a modified-atmosphere package and displayed at
      abusive temperatures.
AB  - Lactic acid bacteria (LAB) can reduce Escherichia coli O157:H7 and Salmonella
      spp. in ground beef during storage. Furthermore, the addition of rosemary
      oleoresin (RO), a natural antioxidant, to ground beef has been shown to increase
      shelf life and is commonly used in modified-atmosphere packaged (MAP) ground
      beef. This study evaluated the effects of LAB and RO treatment on the shelf life
      and stability of MAP ground beef displayed at abusive (10 degrees C) temperatures
      for 36 h. Subjective and objective sensory analyses were conducted to determine
      spoilage endpoints. Trained and consumer panel responses and Hunter lightness
      (L*), redness (a*), and yellowness (b*) values were not affected (P = 0.62, 0.66,
      0.45) by LAB addition, although RO inclusion improved (P < 0.05) lean color.
      Ground beef with LAB and RO had significantly less (P < 0.0001) thiobarbituric
      acid reactive substance values than control ground beef, indicating decreased
      lipid oxidation. Additionally, RO inclusion reduced (P < 0.0001) off odors, as
      determined by trained and consumer odor panelists. Overall, the addition of LAB
      did not negatively affect beef color, odor, or oxidative rancidity, suggesting
      that LAB can be added to ground beef in MAP packaging as a processing
      intervention without detrimentally affecting shelf life or stability.

PMID- 22648757
TI  - Assessment and incidence of salivary leak following laryngectomy.
AB  - OBJECTIVES/HYPOTHESIS: To determine the incidence and risk factors of
      pharyngocutaneous fistula formation in patients undergoing either primary or
      salvage laryngectomies and evaluate the role of barium esophagram in these
      patients. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records of
      259 patients who underwent total laryngectomy between 2003 and 2009 at our
      institution were reviewed. Risk factors for fistula formation were analyzed,
      including primary treatment modality, comorbidities, and operative details, which
      included use of a free flap for closure, concurrent neck dissections, margin
      status, and preoperative tracheostomy. The length of time until leak,
      postoperative swallow study results, and fistula management strategies were also
      assessed. RESULTS: Fifty-five patients developed a pharyngocutaneous fistula
      (overall incidence, 21%) in a median time of 12 days (range, 4-105 days). Twenty
      of these patients underwent laryngectomy as their initial treatment modality, and
      35 had failed previous radiotherapy. Fistula formation was significantly higher
      in salvage surgery patients (P = .03), particularly those with hypothyroidism (P
      < .0002). A barium swallow performed at approximately 1 week after laryngectomy
      demonstrated a sensitivity of 26% with a specificity of 94%. Sixty-two percent of
      the fistulas healed with conservative measures only. CONCLUSIONS: Our data
      confirmed that previous radiotherapy and hypothyroidism, particularly in salvage
      laryngectomy patients, are important significant predictors of postoperative
      pharyngocutaneous fistula. The use of a postoperative barium swallow in these
      patients may be useful but was not found to be highly sensitive in predicting who
      will develop a clinically evident leak and should be used with caution.

PMID- 22648760
TI  - Analysis of the psychometric properties of the Interpersonal Needs Questionnaire
      (INQ) among community-dwelling older adults.
AB  - OBJECTIVES: This study evaluated the structure and validity of the use of the 18
      item Interpersonal Needs Questionnaire (INQ-18), a measure of thwarted
      belongingness (TB) and perceived burdensomeness (PB), among older adults. METHOD:
      Community-dwelling older adults (N = 284; mean age = 73 years; age range = 64-96
      years; 56% women) anonymously completed a questionnaire packet. RESULTS:
      Principal axis factor analysis indicated that two factors should be retained.
      Items in the first factor reflected the concept of TB, whereas items in the
      second factor were consistent with the concept of PB. Both factors had medium-to
      large positive correlations with hopelessness, depression, suicide ideation, and
      low meaning in life, providing evidence for convergent validity. CONCLUSIONS:
      Findings from this study support the use of the INQ-18 among community-dwelling
      older adults.

PMID- 22648761
TI  - Fabrication of microgel particles with complex shape via selective polymerization
      of aqueous two-phase systems.
AB  - Microgel particles are formed from aqueous-two-phase-system (ATPS) droplets in
      poly(dimethylsiloxane) (PDMS) microfluidic devices. The droplets consist of a
      dextran core and a photopolymerizable poly(ethylene glycol) diacrylate (PEGDA)
      shell. Upon UV exposure, the ATPS droplets undergo a shape-transformation
      yielding PEGDA microgel particles containing a socket.

PMID- 22648762
TI  - Morphometry of corpus callosum in Williams syndrome: shape as an index of neural
      development.
AB  - Brain abnormalities in Williams syndrome (WS) have been consistently reported,
      despite few studies have devoted attention to connectivity between different
      brain regions in WS. In this study, we evaluated corpus callosum (CC)
      morphometry: bending angle, length, thickness and curvature of CC using a new
      shape analysis method in a group of 17 individuals with WS matched with a
      typically developing group. We used this multimethod approach because we
      hypothesized that neurodevelopmental abnormalities might result in both volume
      changes and structure deformation. Overall, we found reduced absolute CC cross
      sectional area and volume in WS (mean CC and subsections). In parallel, we
      observed group differences regarding CC shape and thickness. Specifically, CC of
      WS is morphologically different, characterized by a larger bending angle and
      being more curved in the posterior part. Moreover, although CC in WS is shorter,
      a larger relative thickness of CC was found in all callosal sections. Finally,
      groups differed regarding the association between CC measures, age, white matter
      volume and cognitive performance. In conclusions, abnormal patterns of CC
      morphology and shape may be implicated in WS cognitive and behavioural phenotype.

PMID- 22648763
TI  - It covers a broad spectrum of clinical and basic neuroscience.

PMID- 22648766
TI  - Candidate diseases for prenatal gene therapy.
AB  - Prenatal gene therapy aims to deliver genes to cells and tissues early in
      prenatal life, allowing correction of a genetic defect, before irreparable tissue
      damage has occurred. In contrast to postnatal gene therapy, prenatal application
      may target genes to a large population of stem cells, and the smaller fetal size
      allows a higher vector to target cell ratio to be achieved. Early gestation
      delivery may allow the development of immune tolerance to the transgenic protein,
      which would facilitate postnatal repeat vector administration if needed.
      Moreover, early delivery would avoid anti-vector immune responses which are often
      acquired in postnatal life. The NIH Recombinant DNA Advisory Committee considered
      that a candidate disease for prenatal gene therapy should pose serious morbidity
      and mortality risks to the fetus or neonate, and not have any effective postnatal
      treatment. Prenatal gene therapy would therefore be appropriate for life
      threatening disorders, in which prenatal gene delivery maintains a clear
      advantage over cell transplantation or postnatal gene therapy. If deemed safer
      and more efficacious, prenatal gene therapy may be applicable for nonlethal
      conditions if adult gene transfer is unlikely to be of benefit. Many candidate
      diseases will be inherited congenital disorders such as thalassaemia or lysosomal
      storage disorders. However, obstetric conditions such as fetal growth restriction
      may also be treated using a targeted gene therapy approach. In each disease, the
      condition must be diagnosed prenatally, either via antenatal screening and
      prenatal diagnosis, for example, in the case of hemophilias, or by ultrasound
      assessment of the fetus, for example, congenital diaphragmatic hernia. In this
      chapter, we describe some examples of the candidate diseases and discuss how a
      prenatal gene therapy approach might work.

PMID- 22648765
TI  - The concept of prenatal gene therapy.
AB  - This introductory chapter provides a short review of the ideas and practical
      approaches that have led to the present and perceived future development of
      prenatal gene therapy. It summarizes the advantages and the potential adverse
      effects of this novel preventive and therapeutic approach to the management of
      prenatal diseases. It also provides guidance to the range of conditions to which
      prenatal gene therapy may be applied and to the technical approaches, vectors,
      and societal/ethical considerations for this newly emerging field of Fetal
      Medicine.

PMID- 22648767
TI  - Vector systems for prenatal gene therapy: choosing vectors for different
      applications.
AB  - This chapter gives a comparative review of the different vector systems applied
      to date in prenatal gene therapy experiments highlighting the need for
      versatility and choice for application in accordance with the actual aim of the
      study. It reviews the key characteristics of the four main gene therapy vector
      systems and gives examples for their successful application in prenatal gene
      therapy experiments.

PMID- 22648768
TI  - Vector systems for prenatal gene therapy: principles of adenovirus design and
      production.
AB  - Adenoviruses have many attributes, which have made them one of the most widely
      investigated vectors for gene therapy applications. These include ease of genetic
      manipulation to produce replication-deficient vectors, ability to readily
      generate high titer stocks, efficiency of gene delivery into many cell types, and
      ability to encode large genetic inserts. Recent advances in adenoviral vector
      engineering have included the ability to genetically manipulate the tropism of
      the vector by engineering of the major capsid proteins, particularly fiber and
      hexon. Furthermore, simple replication-deficient adenoviral vectors deleted for
      expression of a single gene have been complemented by the development of systems
      in which the majority of adenoviral genes are deleted, generating sophisticated
      Ad vectors which can mediate sustained transgene expression following a single
      delivery. This chapter outlines methods for developing simple transgene over
      expressing Ad vectors and detailed strategies to engineer mutations into the
      major capsid proteins.

PMID- 22648769
TI  - Vector systems for prenatal gene therapy: principles of retrovirus vector design
      and production.
AB  - Vectors derived from the Retroviridae family have several attributes required for
      successful gene delivery. Retroviral vectors have an adequate payload size for
      the coding regions of most genes; they are safe to handle and simple to produce.
      These vectors can be manipulated to target different cell types with low
      immunogenicity and can permanently insert genetic information into the host
      cells' genome. Retroviral vectors have been used in gene therapy clinical trials
      and successfully applied experimentally in vitro, in vivo, and in utero.

PMID- 22648770
TI  - Vector systems for prenatal gene therapy: principles of adeno-associated virus
      vector design and production.
AB  - Vectors based on adeno-associated virus (AAV) show great promise for safe,
      efficacious therapeutic gene transfer in extensive pre-clinical data and,
      recently, in clinical trials. Careful vector design and choice from a range of
      natural or synthetic pseudotypes allow targeted, efficient, and sustained
      expression of therapeutic genes. The efficiency of gene delivery can be further
      enhanced through the use of drug pre-treatment or co-infection with a suitable
      helper virus. This chapter describes current best practice for AAV production,
      including complete methods for: (1) efficient generation of vector without the
      use of helper viruses, simplifying the transition to GMP-grade production for
      clinical applications; (2) efficient and easily scalable purification of the
      virus by affinity chromatography, allowing rapid production of highly
      concentrated, high titre stocks; (3) reliable quantification and assaying of
      viral stocks, along with short- and long-term storage considerations.

PMID- 22648771
TI  - Vector systems for prenatal gene therapy: principles of non-viral vector design
      and production.
AB  - Gene therapy vectors based on viruses are the most effective gene delivery
      systems in use today and although efficient at gene transfer their potential
      toxicity (Hacein-Bey-Abina et al., Science 302:415-419, 2003) provides impetus
      for the development of safer non-viral alternatives. An ideal vector for human
      gene therapy should deliver sustainable therapeutic levels of gene expression
      without affecting the viability of the host at either the cellular or somatic
      level. Vectors, which comprise entirely human elements, may provide the most
      suitable method of achieving this. Non-viral vectors are attractive alternatives
      to viral gene delivery systems because of their low toxicity, relatively easy
      production, and great versatility. The development of more efficient,
      economically prepared, and safer gene delivery vectors is a crucial prerequisite
      for their successful clinical application and remains a primary strategic task of
      gene therapy research.

PMID- 22648772
TI  - Use of manipulated stem cells for prenatal therapy.
AB  - Prenatal stem cell therapy has broad potential for therapeutic application. "Stem
      cells" of interest include multipotent adult-derived stem cells, cord blood,
      amniotic fluid, or fetal stem cells, and embryonic or induced pluripotent stem
      cells. Potential manipulations of stem cells prior to their administration may
      include harvest, processing, enrichment, expansion, and genetic transduction. A
      complete description of the methodology related to all of the above is well
      beyond the scope of this chapter. In the interest of practical application and
      proven efficacy, we limit our description to adult-derived hematopoietic stem
      cells (HSCs) and their application to in utero transplantation with or without
      HSC-targeted gene transfer.

PMID- 22648773
TI  - Animal models for prenatal gene therapy: choosing the right model.
AB  - Testing in animal models is an essential requirement during development of
      prenatal gene therapy for -clinical application. Some information can be derived
      from cell lines or cultured fetal cells, such as the efficiency of gene transfer
      and the vector dose that might be required. Fetal tissues can also be maintained
      in culture for short periods of time and transduced ex vivo. Ultimately, however,
      the use of animals is unavoidable since in vivo experiments allow the length and
      level of transgene expression to be measured, and provide an assessment of the
      effect of the delivery procedure and the gene therapy on fetal and neonatal
      development. The choice of animal model is determined by the nature of the
      disease and characteristics of the animal, such as its size, lifespan, and
      immunology, the number of fetuses and their development, parturition, and the
      length of gestation and the placentation. The availability of a disease model is
      also critical. In this chapter, we discuss the various animal models that can be
      used and consider how their characteristics can affect the results obtained. The
      projection to human application and the regulatory hurdles are also presented.

PMID- 22648774
TI  - Animal models for prenatal gene therapy: rodent models for prenatal gene therapy.
AB  - Fetal gene transfer has been studied in various animal models, including rabbits,
      guinea pigs, cats, dogs, and nonhuman primate; however, the most common model is
      the rodent, particularly the mouse. There are numerous advantages to mouse
      models, including a short gestation time of around 20 days, large litter size
      usually of more than six pups, ease of colony maintenance due to the small
      physical size, and the relatively low expense of doing so. Moreover, the mouse
      genome is well defined, there are many transgenic models particularly of human
      monogenetic disorders, and mouse-specific biological reagents are readily
      available. One criticism has been that it is difficult to perform procedures on
      the fetal mouse with suitable accuracy. Over the past decade, accumulation of
      technical expertise and development of technology such as high-frequency
      ultrasound have permitted accurate vector delivery to organs and tissues. Here,
      we describe our experiences of gene transfer to the fetal mouse with and without
      ultrasound guidance from mid to late gestation. Depending upon the vector type,
      the route of delivery and the age of the fetus, specific or widespread gene
      transfer can be achieved, making fetal mice excellent models for exploratory
      biodistribution studies.

PMID- 22648764
TI  - Beta amyloid, tau, neuroimaging, and cognition: sequence modeling of biomarkers
      for Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is associated with a cascade of pathological events
      involving formation of amyloid-based neuritic plaques and tau-based
      neurofibrillary tangles, changes in brain structure and function, and eventually,
      cognitive impairment and functional disability. The precise sequence of when each
      of these disease markers becomes abnormal is not yet clearly understood. The
      present study systematically tested the relationship between classes of
      biomarkers according to a proposed model of temporal sequence by Jack et al.
      (Lancet Neurology 9:119-128, 2010). We examined temporal relations among four
      classes of biomarkers: CSF Abeta, CSF tau, neuroimaging variables (hippocampal
      volume, ventricular volume, FDG PET), and cognitive variables (memory and
      executive function). Random effects modeling of longitudinal data obtained from
      the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used to test
      hypotheses that putative earlier markers of AD predicted change in later markers,
      and that intervening markers reduced effects of earlier on later markers.
      Specifically, we hypothesized that CSF tau would explain CSF Abeta's relation to
      neuroimaging and cognitive variables, and neuroimaging variables would explain
      tau's relation to cognitive variables. Consistent with hypotheses, results
      indicated that CSF Abeta effects on cognition change were substantially
      attenuated by CSF tau and measures of brain structure and function, and CSF tau
      effects on cognitive change were attenuated by neuroimaging variables. Contrary
      to hypotheses, CSF Abeta and CSF tau were observed to have independent effects on
      neuroimaging and CSF tau had a direct effect on baseline cognition independent of
      brain structure and function. These results have implications for clarifying the
      temporal sequence of AD changes and corresponding biomarkers.

PMID- 22648775
TI  - Animal models for prenatal gene therapy: the sheep model.
AB  - Large animal experiments are vital in the field of prenatal gene therapy, to
      allow translation from small animals into man. Sheep provide many advantages for
      such experiments. They have been widely used in research into fetal physiology
      and pregnancy and the sheep fetus is a similar size to that in the human. Sheep
      are tolerant to in utero manipulations such as fetoscopy or even hysterotomy, and
      they are cheaper and easier to maintain than non-human primates. In this chapter,
      we describe the animal husbandry involved in generating time-mated sheep
      pregnancies, the large number of injection routes in the fetus that can be
      achieved using ultrasound or fetoscopic-guided injection, and laparotomy when
      these more minimally invasive routes of injection are not feasible.

PMID- 22648776
TI  - Animal models for prenatal gene therapy: the nonhuman primate model.
AB  - Intrauterine gene therapy (IUGT) potentially enables the treatment and possible
      cure of monogenic -diseases that cause severe fetal damage. The main benefits of
      this approach will be the ability to correct the disorder before the onset of
      irreversible pathology and inducing central immune tolerance to the vector and
      transgene if treatment is instituted in early gestation. Cure has been
      demonstrated in small animal models, but because of the significant differences
      in immune ontogeny and the much shorter gestation compared to humans, it is
      unlikely that questions of long-term efficacy and safety will be adequately
      addressed in rodents. The nonhuman primate (NHP) allows investigation of key
      issues, in particular, the different outcomes in early and late-gestation IUGT
      associated with different stages of immune maturity, longevity of transgene
      expression, and delayed-onset adverse events in treated offspring and mothers
      including insertional mutagenesis. Here, we describe a model based on the Macaca
      fascicularis using ultrasound and fetoscopic approaches to systemic vector
      delivery and the processes involved in vector administration and longitudinal
      analyses.

PMID- 22648777
TI  - Choice of surrogate and physiological markers for prenatal gene therapy.
AB  - Surrogate genetically encoded markers have been utilized in order to analyze gene
      transfer efficacy, location, and persistence. These marker genes have greatly
      accelerated the development of gene transfer vectors for the ultimate application
      of gene therapy using therapeutic genes. They have also been used in many other
      applications, such as gene marking in order to study developmental cell lineages,
      to track cell migration, and to study tumor growth and metastasis. This chapter
      aims to describe the analysis of several commonly used marker genes: green
      fluorescent protein (GFP), beta-galactosidase, firefly luciferase, human factor
      IX, and alkaline phosphatase. The merits and disadvantages of each are briefly
      discussed. In addition a few short examples are provided for continual and
      endpoint analysis in different disease models including hemophilia, cystic
      fibrosis, ornithine transcarbamylase deficiency and Gaucher disease.

PMID- 22648778
TI  - Monitoring for potential adverse effects of prenatal gene therapy: use of large
      animal models with relevance to human application.
AB  - Safety is an absolute prerequisite for introducing any new therapy, and the need
      to monitor the consequences of administration of both vector and transgene to the
      fetus is particularly important. The unique features of fetal development that
      make it an attractive target for gene therapy, such as its immature immune system
      and rapidly dividing populations of stem cells, also mean that small
      perturbations in pregnancy can have significant short- and long-term
      consequences. Certain features of the viral vectors used, the product of the
      delivered gene, and sometimes the invasive techniques necessary to deliver the
      construct to the fetus in utero have the potential to do harm. An important goal
      of prenatal gene therapy research is to develop clinically relevant techniques
      that could be applied to cure or ameliorate human disease in utero on large
      animal models such as sheep or nonhuman primates. Equally important is the use of
      these models to monitor for potential adverse effects of such interventions.
      These large animal models provide good representation of individual patient-based
      investigations. However, analyses that require defined genetic backgrounds, high
      throughput, defined variability and statistical analyses, e.g. for initial
      studies on teratogenic and oncogenic effects, are best performed on larger groups
      of small animals, in particular mice. This chapter gives an overview of the
      potential adverse effects in relation to prenatal gene therapy and describes the
      techniques that can be used experimentally in a large animal model to monitor the
      potential adverse consequences of prenatal gene therapy, with relevance to
      clinical application. The sheep model is particularly useful to allow serial
      monitoring of fetal growth and well-being after delivery of prenatal gene
      therapy. It is also amenable to serially sampling using minimally invasive and
      clinically relevant techniques such as ultrasound-guided blood sampling. For more
      invasive long-term monitoring, we describe telemetric techniques to measure the
      haemodynamics of the mother or fetus, for example, that interferes minimally with
      normal animal behaviour. Implanted catheters can also be used for serial fetal
      blood sampling during gestation. Finally, we describe methods to monitor events
      around birth and long-term neonatal follow-up that are important when considering
      human translation of this therapy.

PMID- 22648779
TI  - Monitoring for potential adverse effects of prenatal gene therapy: mouse models
      for developmental aberrations and inadvertent germ line transmission.
AB  - So far no systematic studies have been conducted to investigate developmental
      aberrations after prenatal gene transfer in mice. Here, we suggest procedures for
      such observations to be applied, tested and improved in further in utero gene
      therapy experiments. They are based on our own experience in husbandry for
      transgenic human diseases mouse models and breading, rearing, and observing mice
      after fetal gene transfer as well as on the systematic screens for monitoring of
      knock-out mutant mouse phenotypes established in international mutagenesis
      projects (EUMORPHIA and EUMODIC and subsequently the International Mouse
      Phenotyping Consortium). We also describe here the analysis procedures for
      detection of germ line mutations based on quantitative PCR (qPCR) by sperm-DNA
      analysis and breeding studies.

PMID- 22648781
TI  - Risks, benefits and ethical, legal, and societal considerations for translation
      of prenatal gene therapy to human application.
AB  - The still experimental nature of prenatal gene therapy carries a certain degree
      of risk, both for the pregnant mother as well as for the fetus. Some of the risks
      are procedural hazards already known from more conventional fetal medicine
      interventions. Others are more specific to gene therapy such as the potential for
      interference with normal fetal development, the possibility of inadvertent germ
      line gene transfer, and the danger of oncogenesis. This chapter reviews the
      potential risks in relation to the expected benefits of prenatal gene therapy. It
      discusses the scientific, ethical, legal, and social implications of this novel
      preventive approach to genetic disease and outlines preconditions to be met in
      preparation for a potential future clinical application.

PMID- 22648780
TI  - Monitoring for potential adverse effects of prenatal gene therapy: genotoxicity
      analysis in vitro and on small animal models ex vivo and in vivo.
AB  - Gene delivery by integrating vectors has the potential to cause genotoxicity in
      the host by insertional mutagenesis (IM). Previously, the risk of IM by
      replication incompetent retroviral vectors was believed to be small. However, the
      recent observation of leukaemic events due to gamma retroviral vector insertion
      and activation of the LMO-2 proto-oncogene in patients enrolled in the French and
      British gene therapy trials for X-SCID demonstrates the need to understand vector
      associated genotoxicity in greater detail. These findings have led to the
      development of in vitro, ex vivo, and in vivo assays designed to predict
      genotoxic risk and to further our mechanistic understanding of this process at
      the molecular level. In vitro assays include transformation of murine
      haematopoietic stem cells by integrating retroviral (RV) or lentiviral (LV)
      vectors and measurement of cell survival resulting from transformation due to
      integration mainly into the Evi1 oncogene. Ex vivo assays involve harvesting
      haematopoietic stem cells from mice followed by gene transfer and re-infusion of
      RV or LV infected cells to reconstitute the immune system. Insertional
      mutagenesis is then determined by analysis of clonally dominant populations of
      cells. The latter model has also been made highly sensitive using cells from mice
      predisposed to oncogenesis by lack of the P53 and Rb pathways. Our investigations
      on fetal gene therapy discovered a high incidence of liver tumour development
      that appears to be associated with vector insertions into cancer-related genes.
      Many genes involved in growth and differentiation are actively transcribed in
      early developmental and are therefore in an open chromatin configuration, which
      favours provirus insertion. Some of these genes are known oncogenes or anti
      oncogenes and are not usually active during adulthood. We found that in utero
      injection of primate HIV-1, HR'SIN-cPPT-S-FIX-W does not result in oncogenesis as
      opposed to administration of non-primate equine infectious anaemia virus (EIAV),
      SMART 2 lentivirus vectors and, most recently, the non-primate pLIONhAATGFP (FIV)
      vector, which both give rise to high frequency hepatocellular carcinoma. The
      peculiar integration pattern into cancer-related genes observed in this model
      makes the fetal mouse a sensitive tool, not only to investigate long-term vector
      mediated gene expression, but also vector safety in an in vivo system with
      minimal immunological interference. The identification of distinct differences in
      genotoxic outcome between the applied vector systems i.e. EIAV or FIV vectors
      versus HIV may indicate a particular biosafety profile of the HIV-1-based vector,
      which renders it potentially suitable for safe prenatal gene therapy.

PMID- 22648782
TI  - Toll-like receptor 4 ligation confers chemoresistance to docetaxel on PC-3 human
      prostate cancer cells.
AB  - Recent studies have indicated that Toll-like receptors (TLRs) are implicated in
      the development of chemoresistance in cancer cells. TLR4 has been shown to be
      highly expressed in prostate cancer cells and contributes to tumor cell survival
      and invasion. In this study, we aimed to investigate the role of TLR4 signaling
      in the chemoresistance of prostate cancer cells. We showed that ligation of TLR4
      with lipopolysaccharide (LPS) abrogated docetaxel-induced growth suppression in
      PC-3 prostate cancer cells, with an increase in the half-maximal inhibitory
      concentration. Downregulation of TLR4 using small-interference RNA sensitized PC
      3 cells to docetaxel-induced apoptosis as determined by annexin V staining and
      poly (ADP-ribose) polymerase cleavage, which was coupled with increased Bax
      expression and decreased Bcl-2. TLR4 ligation resulted in a marked increase in
      the phosphorylation of phosphatidylinositol 3-kinase (PI3-K) and Akt. The
      pretreatment with a PI3-K inhibitor LY294002 reduced LPS-mediated resistance to
      docetaxel, significantly decreasing the viability of PC-3 cells. Our data show
      that TLR4 ligation contributes to the chemosensitivity of prostate cancer cells,
      which at least partially involves the activation of the PI3-K/Akt pathway.
      Therefore, TLR4 signaling may represent a promising target for the improvement of
      chemotherapeutic efficacy in prostate cancer.

PMID- 22648783
TI  - Ultrasound echoes as biometric navigators.
AB  - We demonstrate a new method of using ultrasound data to achieve prospective
      motion compensation in MRI, especially for respiratory motion during
      interventional MRI procedures in moving organs such as the liver. The method
      relies on fingerprint-like biometrically distinct ultrasound echo patterns
      produced by different locations in tissue, which are collated with geometrical
      information from MRI during a training stage to form a mapping table that relates
      ultrasound measurements to positions. During prospective correction, the system
      makes frequent ultrasound measurements and uses the map to determine the
      corresponding position. Results in motorized linear motion phantoms and freely
      breathing animals indicate that the system performs well. Apparent motion is
      reduced by up to 97.8%, and motion artifacts are reduced or eliminated in two
      dimensional spoiled gradient-echo images. The motion compensation is sufficient
      to permit MRI thermometry of focused ultrasound heating during respiratory-like
      motion, with results similar to those obtained in the absence of motion. This new
      technique may have applications for MRI thermometry and other dynamic imaging in
      the abdomen during free breathing.

PMID- 22648784
TI  - Dynamics of presynaptic protein recruitment induced by local presentation of
      artificial adhesive contacts.
AB  - In this study, we introduce a novel approach to induce and observe the formation
      of presynaptic compartments in axons through a combination of atomic force
      microscopy (AFM) and fluorescence microscopy. First, we use a poly-D-lysine
      coated bead attached to an AFM tip to induce the recruitment of two synaptic
      proteins, bassoon and synaptophysin, and measure their absolute arrival times to
      the presynaptic department. We find that bassoon arrives before synaptophysin.
      Second, we observe the formation of very long (several 10s of MUm), structured,
      protein-containing membranous strings as the AFM tip was withdrawn from the axon.
      It is conceivable that these strings might be a novel mechanism by which new
      neurites or branch points along existing neurites may be generated in situ.

PMID- 22648785
TI  - Theoretical study of structure, bonding, and electronic behavior of novel
      sandwich compounds M3(C6R6)2 (M = Ni, Pd, Pt; R = H, F).
AB  - The correlations between the structural and electronic properties of the
      monolayer clusters M3 (where M = Ni, Pd, Pt) and the sandwich complexes M3(C6R6)2
      (where M = Ni, Pd, Pt; R = H, F) were studied by performing quantum-chemical
      calculations. All of the sandwich complexes are strongly donating and
      backdonating metal-ligand bonding structures. The influence of the ligand as well
      as significant variations in the M-C, M-M, and C-C bond lengths and binding
      energies were examined to obtain a qualitative and quantitative picture of the
      intramolecular interactions in C6R6-M3. Our theoretical investigations show that
      the binding energies of these sandwich complexes gradually decrease from Ni to Pt
      as well as from H to F, which can be explained via the frontier orbitals of the
      clusters M3 and C6R6.

PMID- 22648786
TI  - Theoretical studies of -NH2 and -NO2 substituted dipyridines.
AB  - In this work, the experimental synthesized bipyridines 3,3'-Dinitro-2,2'
      bipyridine (DNBPy), 3,3'-Dinitro-2,2'-bipyridine-1,1'-dioxide (DNBPyO), and (3
      Nitro-2-pyridyl)(5-nitro-2-pyridyl) amine (NPyA), and a set of designed
      dipyridines that have similar frameworks but different linkages and substituents
      with NPyA were studied theoretically at the B3LYP/6-31G* level of density
      functional theory. The gas-phase heats of formation were predicted based on the
      isodesmic reactions and the condensed-phase heats of formation and heats of
      sublimation were estimated in the framework of the Politzer approach. The crystal
      densities have been computed from molecular packing. Results show that this
      method gives a good estimation of density in comparison with the available
      experimental data for DNBPy, DNBPyO, and NPyA. The predicted detonation
      velocities and pressures indicate that the performance of dipyridines linked with
      -O-, -NH-, or -CH2- bridges have not been improved compared with that of the
      directly linked dipyridines, but all derivatives have better detonation
      properties than DNBPy, DNBPyO, and NPyA because of the presence of more nitro
      groups. An analysis of the bond dissociation energies (BDEs) or the impact
      sensitivity (h50) suggests that introduction of different bridges but not
      substituents has little influence on thermal stability. The calculated h50 may be
      more reliable than BDE for predicting stability. Four bridged bipyridines have
      quite good detonation performance and low sensitivity.

PMID- 22648787
TI  - In silico and in vivo evaluation of flavonoid extracts on CYP2D6-mediated herb
      drug interaction.
AB  - Flavonoid extracts are widely used for preventing and treating ischemic heart
      disease. However, because many flavonoid extracts have been verified to inhibit
      CYP2D6 the main metabolic enzyme for the majority of antiarrhythmics and beta
      blockers, co-administration of flavonoid extracts with these drugs may cause
      adverse herb-drug interaction in clinic. Here, we evaluated 43 common flavonoids
      on CYP2D6 inhibition in sillico and four commercial flavonoid extracts in vivo on
      the pharmacokinetics and pharmacodynamics of metoprolol in rats. Surprisingly, we
      found that the core skeletons of flavonoids instead of their substituents
      determine the extent of inhibiting CYP2D6 by a flavonoid extract. Isoflavones are
      less likely to inhibit CYP2D6, compared with other categories of flavonoids.
      Consistently, co-administration of soy extract that mainly contains isoflavones
      did not significantly increase plasma concentration of metoprolol and alter the
      systolic blood pressure of rats. Our results have implication in rationally
      selecting flavonoid extracts for therapeutic application.

PMID- 22648788
TI  - Chaos in a seasonally perturbed SIR model: avian influenza in a seabird colony as
      a paradigm.
AB  - Seasonality is a complex force in nature that affects multiple processes in wild
      animal populations. In particular, seasonal variations in demographic processes
      may considerably affect the persistence of a pathogen in these populations.
      Furthermore, it has been long observed in computer simulations that under
      seasonal perturbations, a host-pathogen system can exhibit complex dynamics,
      including the transition to chaos, as the magnitude of the seasonal perturbation
      increases. In this paper, we develop a seasonally perturbed Susceptible-Infected
      Recovered model of avian influenza in a seabird colony. Numerical simulations of
      the model give rise to chaotic recurrent epidemics for parameters that reflect
      the ecology of avian influenza in a seabird population, thereby providing a case
      study for chaos in a host- pathogen system. We give a computer-assisted
      exposition of the existence of chaos in the model using methods that are based on
      the concept of topological hyperbolicity. Our approach elucidates the geometry of
      the chaos in the phase space of the model, thereby offering a mechanism for the
      persistence of the infection. Finally, the methods described in this paper may be
      immediately extended to other infections and hosts, including humans. 

PMID- 22648789
TI  - Examining stage IIB survival in a population-based cohort of patients with
      colorectal cancer.
AB  - BACKGROUND: In Nova Scotia, Canada, a previous study of colorectal cancer (CRC)
      cases diagnosed between January 1, 2001, and December 31, 2005, found that
      patients with stage IIB CRC had similar 5-year overall survival (OS) to those
      with stage IIIC cancer. This study sought to examine factors contributing to the
      observed stage IIB outcome, specifically nodal harvest, receipt of chemotherapy,
      and use of a new coding system to derive stage. METHODS: The provincial cancer
      registry identified all CRC cases diagnosed during the study period and staged
      this cohort using the Collaborative Stage (CS) Data Collection System. All
      patients with stage II and III cancer in the cohort were examined. Kaplan-Meier
      (KM) survival curves compared 5-year OS for patients with stage IIB cancer based
      on the factors of interest, and compared patients with stage IIB cancer to those
      with stage IIA and III cancer. RESULTS: OS for patients with stage IIB cancer (n
      = 187) was 44.7%, and differed depending on adequacy of nodal harvest (P = .005)
      and whether pathological or clinical/mixed evidence was used to derive stage (P =
      .013). Pathologically-staged patients with stage IIB cancer who had adequate
      nodal harvest had marginally improved OS compared to pathologically-staged
      patients who had inadequate nodal harvest (P = .07), and improved survival
      compared to patients with clinical/mixed stage (P = .004). Pathologically-staged
      patients with stage IIB cancer with adequate nodal harvest demonstrated similar 5
      year OS to those with stage IIA and III cancer (P = .52 and P = .25,
      respectively). Cox proportional hazards models supported these findings.
      CONCLUSIONS: The inclusion of clinical/mixed evidence into staging classification
      and, perhaps to a lesser extent, the adequacy of nodal harvest appear to
      contribute to the observed worse survival for patients with stage IIB versus
      stage III cancer.

PMID- 22648790
TI  - Thermal effects and morphological aspects of human dentin surface irradiated with
      different frequencies of Er:YAG laser.
AB  - This study reports the effects on micromorphology and temperature rise in human
      dentin using different frequencies of Er:YAG laser. Sixty human dentin fragments
      were randomly assigned into two groups (n = 30): carious or sound dentin. Both
      groups were divided into three subgroups (n = 10), according to the Er:YAG laser
      frequency used: 4, 6, or 10 Hz (energy: 200 mJ; irradiation distance: 12 mm; and
      irradiation time: 20 s). A thermocouple adapted to the tooth fragment recorded
      the initial temperature value ( degrees C); then, the temperature was measured
      after the end of the irradiation (20 s). Morphological analysis was performed
      using images obtained with scanning electron microscope. There was no difference
      between the temperatures obtained with 4 and 6 Hz; the highest temperatures were
      achieved with 10 Hz. No difference was observed between carious and sound dentin.
      Morphological analyses revealed that all frequencies promoted irregular surface
      in sound dentin, being observed more selectively ablation especially in
      intertubular dentin with tubule protrusion. The caries dentin presented flat
      surface for all frequencies used. Both substrates revealed absence of any signs
      of thermal damage. It may be concluded that the parameters used in this study are
      capable to remove caries lesion, having acceptable limits of temperature rise and
      no significant morphological alterations on dentin surface.

PMID- 22648791
TI  - A change in paradigm: giving back identity to donors in the anatomy laboratory.
AB  - This article describes a paradigm of teaching in the anatomy laboratory where
      students interact with the families of the deceased persons whom they are
      dissecting. This approach focuses learning anatomy and medicine on the patient
      via the implementation of five guiding principles: the First Patient; Knowledge;
      Reflection and Reflective Practice; Treating the Total Patient; and
      Professionalism. Physician training typically begins with cadaveric dissection
      (i.e., dissection of the first patient), and therefore the medical school gross
      anatomy course provides an ideal environment for multifaceted educational
      experiences where cadaveric dissection is used to teach structure and function as
      well as the skills and competencies critical to patient care. Here, these
      principles are described, and the impact on student doctors and outcomes
      discussed. The results suggest that mastery of basic science knowledge and
      competencies, including professionalism, compassion, and leadership skill is
      enhanced by this protocol.

PMID- 22648792
TI  - Automated three-dimensional coded contrast imaging hysterosalpingo-contrast
      sonography: feasibility in office tubal patency testing.
AB  - OBJECTIVE: To evaluate the feasibility of transvaginal hysterosalpingo-contrast
      sonography (HyCoSy) with new automated three-dimensional coded contrast imaging
      (3D-CCI) software in the evaluation of tubal patency and visualization of tubal
      course. METHODS: Patients undergoing HyCoSy with automated 3D-CCI software were
      evaluated prospectively. First, to evaluate the feasibility of 3D visualization
      of tubal course, we performed consecutive volume acquisitions while injecting
      SonoVue contrast agent. We then performed conventional two-dimensional (2D) real
      time HyCoSy to confirm tubal patency status by detection of saline and air
      bubbles moving through the Fallopian tubes and around the ovaries. We also
      evaluated visualization with CCI of the contrast agent around the ovaries, side
      effects and pain during and after the procedure, by visual analog scale (VAS)
      (ranging from 0 to 10, with 0 corresponding to no pain and 10 corresponding to
      maximum pain). RESULTS: A total of 126 patients (252 tubes) underwent 3D-CCI
      HyCoSy followed by 2D real-time HyCoSy. According to the final 2D real-time
      evaluation, bilateral tubal patency was observed in 111 patients, bilateral tubal
      occlusion in four patients and unilateral tubal patency in 11 patients. The
      concordance rate for tubal patency status between the first 3D volume acquisition
      and the final 2D real-time evaluation was 84% and that between the second 3D
      volume acquisition and the final 2D real-time evaluation was 97%. A pain score >5
      on VAS was recorded in 58% of patients during the procedure, but a pain score <=
      5 was recorded in 85.7% of patients immediately after the procedure. CONCLUSIONS:
      HyCoSy with automated 3D-CCI technology retains the advantages of conventional 2D
      HyCoSy while overcoming the disadvantages. 2D HyCoSy is highly observer-dependent
      and is only accurate in the hands of experienced investigators; by obtaining a
      volume of the uterus and tubes, automated 3D volume acquisition permits
      visualization of the tubes in the coronal view and of the tubal course in 3D
      space, and should allow less experienced operators to evaluate tubal patency
      status relatively easily.

PMID- 22648793
TI  - Professor Valentino J. Stella: scientist, mentor, entrepreneur, family man, and
      giant in pharmaceutical chemistry.

PMID- 22648794
TI  - In vitro and in vivo interrogation of bio-sprayed cells.
AB  - Bio-sprays can directly form pre-organized cell-bearing structures for
      applications ranging from engineering functional tissues to the forming of
      cultures, most useful for modeling disease, to the discovery and development of
      drugs. Bio-electrosprays and aerodynamically assisted bio-jets, are leading
      approaches that have been demonstrated as having far-reaching ramifications for
      regenerative biology and medicine.

PMID- 22648796
TI  - Serum insulin-like growth factor-1 concentrations are reduced in severely obese
      women and raise after weight loss induced by laparoscopic adjustable gastric
      banding.
AB  - BACKGROUND: Obesity is associated with abnormalities of the growth
      hormone/insulin-like growth factor-1 (GH/IGF-1) axis. The role of serum IGF-1
      measurement for recognition of hypothalamic-pituitary diseases in obesity is
      still a matter of debate. METHODS: This study evaluated the serum levels of IGF-1
      in a population of severely obese women before and after long-term weight loss
      obtained by laparoscopic adjustable gastric banding (LAGB). Eighty obese women
      with body mass index (BMI) of more than 34 kg/m(2) and 80 unrelated age-matched
      lean controls were enrolled. IGF-1 serum levels were measured together with BMI,
      liver volume, and intra-abdominal fat thickness assessed by ultrasound.
      Evaluation was repeated 2 years after LAGB. RESULTS: Our results showed that mean
      IGF-1 levels in obese subjects before LAGB were significantly lower (p < 0.001)
      than that observed in age-matched controls. Age and BMI were independent
      predictors of serum IGF-1 values, overall accounting for 39 % of IGF-1
      variability. The mean IGF-1 concentration significantly increased 2 years after
      LAGB. BMI reduction was independently associated with IGF-1 increase (r = -0.29,
      p < 0.001). For each point of BMI reduction, the mean increase of serum IGF-1 was
      4.39 ng/mL. CONCLUSIONS: (1) Severely obese women have low IGF-1 serum levels
      with respect to normal weight age-matched controls; (2) the extent of IGF-1
      deficiency is proportional to increased BMI; (3) after LAGB a spontaneous raise
      of serum IGF-1 occurs, proportional to the extent of weight reduction; and (4)
      serum IGF-1 in severely obese subjects may have a limited value for detection of
      hypothalamic-pituitary diseases.

PMID- 22648797
TI  - Laparoscopic greater curvature plication (LGCP) for treatment of morbid obesity
      in a series of 244 patients.
AB  - BACKGROUND: Laparoscopic greater curvature plication (LGCP) is a new
      metabolic/bariatric surgical procedure that requires no resection, bypass, or
      implantable device. We report LGCP outcomes in 244 morbidly obese patients.
      METHODS: Between 2010 and 2011, patients underwent LGCP. Body mass index (BMI,
      kilogram per square meter) evolution, excess BMI loss (%EBMIL), excess weight
      loss (%EWL), complications, and type 2 diabetes mellitus (T2DM) changes were
      recorded. Repeated-measures analysis of variance (ANOVA) was used to assess
      weight change at 6, 12, and 18 months. Subgroup analyses were conducted to
      provide benchmark outcomes at 6 months. Logistic regression was used to identify
      characteristics predictive of suboptimal weight loss. RESULTS: Mean baseline BMI
      (+/-SD) was 41.4 +/- 5.5 (80.7 % women, mean age 46.1 +/- 11.0 years, 68 [27.9 %]
      patients had T2DM). Mean operative time was 70.6 min; mean hospitalization, 36 h
      (24-72). Sixty-eight patients (27.9 %) experienced postoperative nausea and/or
      vomiting that was controlled within 36 h. There was no mortality. Major
      complication rate was 1.2 % (n = 3). Repeated-measures ANOVA indicated
      significant weight loss across time points (p < 0.001). At 6 months (n = 105),
      BMI, %EBMIL, and %EWL were 36.1 +/- 4.7, 34.8 +/- 17.3, and 31.8 +/- 15.9.
      Preoperative BMI was the only predictor of weight loss. Patients with BMI <40
      lost more weight than those >=40, although by 9 months, differences were no
      longer significant. In patients with preoperative BMI <40, 18-month %EWL
      approached 50 % and %EBMIL exceeded 50 %. At 6 months, 96.9 % of patients' T2DM
      was significantly improved/resolved. CONCLUSIONS: Over the short term, LGCP
      results in effective weight loss and significant T2DM reduction with a very low
      rate of complications.

PMID- 22648799
TI  - Subsequent publication rate of studies from India presented at the annual
      congresses of SIOP.
AB  - Subsequent publication as a complete manuscript is a desirable end-point for
      studies presented at scientific meetings. Between 2001 and 2005, 191 studies from
      India were presented at annual congresses of the International Society of
      Paediatric Oncology. Of these 24 (12.6%) were published with a median time to
      publication of 20 months. This subsequent publication rate is lower than previous
      reports of SPR for either paediatric or oncological meetings. A lower proportion
      of oral presentations and randomised clinical trials (RCTs) could partly explain
      our findings. Further research is needed to understand barriers to subsequent
      publication of presented data from India.

PMID- 22648798
TI  - alpha-Catulin marks the invasion front of squamous cell carcinoma and is
      important for tumor cell metastasis.
AB  - Squamous cell carcinomas (SCC) comprise the most common types of human epithelial
      cancers. One subtype, head and neck squamous cell carcinoma (HNSCC), is a
      particularly aggressive cancer with poor prognosis due to late diagnosis and
      lymph node metastasis. Of all the processes involved in carcinogenesis, local
      invasion and distant metastasis are clinically the most relevant, but are the
      least well understood on a molecular level. Here, we find that in vivo, the alpha
      catenin homologue-alpha-catulin, a protein originally reported to interact with
      Lbc Rho guanine nucleotide exchange factor, is highly expressed at the tumor
      invasion front and in the metastatic streams of cells in both malignant hHNSCCs
      and a mouse model of oral SCC. Knockdown of alpha-catulin in hHNSCC cell lines
      dramatically decrease the migratory and invasive potential of those cells in
      vitro and metastatic potential in xenotransplants in vivo. Analysis of tumors
      deficient in alpha-catulin showed that the tumor cells are unable to invade the
      surrounding stroma. Accordingly, transcriptional profiling of those tumors
      revealed that alpha-catulin ablation is accompanied by changes in genes involved
      in cell migration and invasion. Interestingly enough, in vitro experiments show
      that an upregulation of alpha-catulin expression correlates with the transition
      of tumor cells from an epithelial to a mesenchymal morphology, as well as an
      upregulation of epithelial-to-mesenchymal transition (EMT) markers vimentin and
      snail. Overall, these results strongly indicate that alpha-catulin contributes to
      the invasive behavior of metastatic cells and may be used as a prognostic marker
      and future therapeutic target for patients with cancer.

PMID- 22648800
TI  - Electrophoretic mobility of partially denatured DNA in a gel: qualitative and
      semiquantitative differences between bubbles and split ends.
AB  - Partially melted DNA is known to exhibit an abrupt decrease of electrophoretic
      mobility in a gel. Although this is the main phenomenon exploited in TGGE/DGGE
      (temperature gradient gel electrophoresis/denaturing gradient gel
      electrophoresis), not much is known about the physical processes responsible for
      the blocking. While there is a commonly used formula for the reduced mobility
      based on the theory of branched polymers, it does not discriminate between
      denatured domains bounded on one (split end) or two sides (bubble). To better
      understand how the blocking occurs in both of these cases, a coarse-grained model
      of DNA gel electrophoresis is simulated using Langevin Dynamics. The simulations
      reveal that the low-field mobility is much more sensitive to denatured domains
      located at the ends of a DNA fragment. A denatured domain occurring at the center
      of a fragment indeed reduces the mobility, but at a much lower rate.

PMID- 22648801
TI  - The use of sigmoid pH gradients in free-flow isoelectric focusing of human
      endothelial cell proteins.
AB  - Prefractionation of proteins enhances the resolution of proteome analysis of
      whole cells. Free-flow electrophoresis (FFE) provides a useful step in various
      prefractionation protocols, since matrix-free isoelectric focusing (FF-IEF)
      performed in this machine enables the enrichment of large, easily absorbable,
      sensitive proteins. The impact of the FFE on the success of a proteome analysis
      depends on the quality of the FF-IEF separation procedure. Therefore, attempts
      are continuously being made to improve FF-IEF. Here, we applied sigmoid pH
      gradients to the prefractionation of endothelial cell proteins. Small steps of pH
      incline between neighboring FFE fractions were established in pH ranges, in which
      the proteins of interest have their pIs. With the help of this advanced
      technology, we separated vimentin and cytoplasmic actin as well as
      triosephosphate isomerase and glyceraldehyde phosphate dehydrogenase
      preparatively, and found a pI of 5.9 +/- 0.2 for nonmuscle myosin.

PMID- 22648802
TI  - Toward a screening method for the analysis of small intact proteins by CE-ESI-TOF
      MS.
AB  - Capillary electrophoresis-mass spectrometry (CE-MS) more and more gains in
      importance as an analytical technique for the identification and characterization
      of intact proteins in the biopharmaceutical area. Thus, a CE-ESI-MS method was
      optimized and validated systematically with respect to the improved screening and
      characterization of intact proteins. The optimization was accomplished by
      variation of different CE-MS parameters, such as capillary coating, background
      electrolyte, sheath liquid, and nebulizer gas pressure, while monitoring both the
      resolution and signal intensities. Achievable separation is discussed
      quantitatively in the context of the coating and the resulting EOF, the protein
      mobilities, and the suction effect of the sprayer. The observed precisions of the
      optimized method regarding the migration times (mean RSD = 1.4%) and peak areas
      (mean RSD = 12.3%) and an extensive principal component analysis revealed that
      the presented method is reliable and useful for the quantitation of intact
      proteins and protein isoforms. The applicability of this method to various
      proteins showing different characteristics (pI value, molecular mass,
      hydrophobicity, etc.) is discussed. The presented method will contribute to the
      improved characterization of a large variety of intact proteins in the biomedical
      and pharmaceutical area.

PMID- 22648803
TI  - A novel multiplex method for the simultaneous detection and relative quantitation
      of pollen allergens.
AB  - Standardization of pollen protein extracts is essential in order to ensure
      efficiency and safety in allergy diagnosis and immunotherapy. In this paper, we
      have optimized a multiplex Western blotting method for the simultaneous detection
      of four olive pollen allergens (Ole e 1, Ole e 2, Ole e 5, and Ole e 9) on a
      single blot using a monoclonal antibody from mouse and three polyclonal
      antibodies raised in rabbit. We utilized unconjugated Fab antibody fragments for
      blocking rabbit primary antibodies, and fluorescence-based detection. These
      changes allowed an accurate and reliable comparative quantitation of these
      allergens among pollen-protein samples from six olive cultivars. In addition, we
      also tested the IgE-binding capacity of these pollen extracts by reprobing the
      same blot with a pool of sera from eight patients allergic to olive and detection
      with enzyme conjugated antibodies. A noticeable variability regarding allergen
      content and IgE-reactivity was found among the olive cultivars analyzed.
      Moreover, we could easily confirm the identity of some of the IgE-binding
      proteins by simply overlapping both fluorescence and chemiluminescence images.
      This method is versatile since it can be applied to other allergogenic plant
      species and extended to other allergens.

PMID- 22648804
TI  - Evaluation of the suitability of archival Bouin-fixed paraffin-embedded tissue
      specimens to proteomic investigation.
AB  - Bouin's solution has been used for over a century as a common fixative in several
      pathology laboratories worldwide. Therefore, a considerable number of Bouin-fixed
      paraffin-embedded (BFPE) tumor samples of various origin are available in
      hospital repositories as a powerful information mine for clinical investigations.
      To date, however, such archived tissues have not been subjected to a systematic
      study aimed to evaluate their potential use in proteomics. In this report, we
      investigated whether archival BFPE tissue specimens could be exploited for
      proteomic studies, upon application of protein extraction and proteomic analysis
      methods previously optimized for formalin-fixed samples. As a result, gastric
      BFPE protein extracts exhibited poor suitability for 2D-PAGE analysis, whereas
      over 300 unique proteins could be successfully detected when extracts were
      subjected to SDS-PAGE followed by LC-MS/MS (GeLC-MS/MS). Among these, several
      known markers for gastric cancer and normal gastric functionality were
      identified, indicative of biological and clinical significance of proteomic data
      mined from BFPE tissues. A quantitative and qualitative comparison of FFPE and
      BFPE tissue proteomes was also performed, and results are reported. In
      conclusion, we demonstrated that BFPE specimens can be analyzed by means of a
      proteomic approach such as GeLC-MS/MS. Although considerable molecular biases and
      technical constraints exist, BFPE tissue archives can be fruitfully exploited for
      gathering proteomic data from particularly precious samples.

PMID- 22648805
TI  - Functional specific roles of H-ras and N-ras. A proteomic approach using knockout
      cell lines.
AB  - Ras small GTPases function as transducers of extracellular signals regulating
      cell survival, growth and differentiation. There are three major ras isoforms: H
      , N- and K-Ras. To improve the understanding of H- and N-Ras protein signalling
      networks, we compared total proteome changes in mouse embryonic fibroblasts knock
      out for H-ras and/or N-ras, using proteomics tools combining 2DE, semi
      quantitative image analysis, in-gel trypsin digestion and mass spectrometry.
      There are four up-regulated proteins due to the loss of expression of H-Ras
      (including cyclin-dependent kinase inhibitor 2A) and eight down-regulated
      (including stress-70 protein, dihydropyrimidinase-related-protein 3, heat shock
      cognate 71 kDa protein, tropomyosin beta chain, Rho GDP-dissociation inhibitor 1)
      and six up-regulated proteins (e.g. leukocyte elastase inhibitor A, L-lactate
      dehydrogenase B chain, c-Myc-responsive protein Rcl, interleukin-1 receptor
      antagonist protein) due to the loss of expression of both N- and H-Ras. Most of
      these proteins are related to Ras signalling in one way or another. Changes in
      expression of some of these proteins were further confirmed by Western blot. This
      proteomic comparative analysis from loss of function of H- and N-Ras knockout
      fibroblasts yields interpretable data to elucidate the differential protein
      expression, and contributes to evaluate the possibilities for physiological and
      therapeutic targets.

PMID- 22648806
TI  - Luminescent iridium(III) complexes as novel protein staining agents.
AB  - This article reports a new class of luminescent metal complexes,
      biscyclometalated iridium(III) complexes with an ancillary bathophenanthroline
      disulfonate ligand, for staining protein bands that are separated by
      electrophoresis. The performances of these novel staining agents have been
      studied in comparison with tris(bathophenanthroline disulfonate) ruthenium(II)
      tetrasodium salt (i.e. RuBPS) using a commercially available imaging system. The
      staining agents showed different limits of detection, linear dynamic ranges, and
      protein-to-protein variations. The overall performances of all three stains were
      found to be better than or equivalent to RuBPS under the experimental conditions.

PMID- 22648807
TI  - Molecular interactions of re-released proteins in electrophoresis of human
      erythrocytes.
AB  - Recently, we found that hemoglobin (Hb) could be re-released from live
      erythrocytes during electrophoresis release test (ERT). The re-released Hb
      displays single-band and multiple-band re-release types, but its exact mechanism
      is not well understood. In this article, the protein components of the single
      band re-released Hb were examined. First, the re-released band of erythrocytes
      and the corresponding band of hemolysate, which was used as control, were cut out
      from starch-agarose mixed gel. Next, proteins were recovered from the starch
      agarose mixed gel by freeze-thaw method. After condensing in a vacuum freeze
      drier, the samples were loaded onto a 5-12% SDS-PAGE. After electrophoresis,
      three protein bands (16, 28.9, and 29.3 kDa) emerged from the erythrocytes re
      released Hb single-band (R-R), but only one band (29.3 kDa) emerged from the
      corresponding hemolysate control band (H-R). Finally, these bands were analyzed
      by MALDI-TOF MS. The results showed that these proteins were beta-globin (16
      kDa), carbonic anhydrase 1 (CA1, 28.9 kDa), and carbonic anhydrase 2 (CA2, 29.3
      kDa). Because CA2 exists in both erythrocytes re-released band and hemolysate
      control band, we conclude that the single-band re-released Hb is mainly composed
      of HbA and CA1. Studying the possible interaction between HbA and CA1 will help
      us further understand the in vivo function of Hb.

PMID- 22648808
TI  - Comparative fluorescence two-dimensional gel electrophoresis using a gel strip
      sandwich assembly for the simultaneous on-gel generation of a reference protein
      spot grid.
AB  - The comparison of proteins separated on 2DE is difficult due to gel-to-gel
      variability. Here, a method named comparative fluorescence gel electrophoresis
      (CoFGE) is presented, which allows the generation of an artificial protein grid
      in parallel to the separation of an analytical sample on the same gel. Different
      fluorescent stains are used to distinguish sample and marker on the gel. The
      technology combines elements of 1DE and 2DE. Special gel combs with V-shaped
      wells are placed in a stacking gel above the pI strip. Proteins separated on the
      pI strip are electrophoresed at the same time as marker proteins (commercially
      available purified protein of different molecular weight) placed in V-wells. In
      that way, grids providing approximately 100 nodes as landmarks for the
      determination of protein spot coordinates are generated. Data analysis is
      possible with commercial 2DE software capable of warping. The method improves
      comparability of 2DE protein gels, because they are generated in combination with
      regular in-gel anchor points formed by protein standards. This was shown here for
      two comparative experiments with three gels each using Escherichia coli lysate.
      For a set of 47 well-defined samples spots, the deviation of the coordinates was
      improved from 7% to less than 1% applying warping using the marker grid.
      Conclusively, as long as the same protein markers, the same size of pI-strips and
      the same technology are used, gel matching is reproducibly possible. This is an
      important advancement for projects involving comparison of 2DE-gels produced over
      several years and in different laboratories.

PMID- 22648810
TI  - Rapid separations of nile blue stained microorganisms as cationic charged species
      by chip-CE with LIF.
AB  - Rapid detection of microorganisms by alternative methods is desirable.
      Electromigration separation methods have the capability to separate
      microorganisms according to their charge and size and laser-induced fluorescence
      (LIF) detection have single-cell detection capability. In this work, a new
      combined separation and detection scheme was introduced using chip-based
      capillary electrophoresis (chip-CE) platform with LIF detection. Three
      microorganisms Escherichia coli, Staphylococcus aureus, and Candida albicans were
      selected as representatives of Gram-positive bacteria, Gram-negative bacteria,
      and fungi. While their cells carry an overall negative charge in neutral to
      alkaline pH, staining them with nile blue (NB) provided highly sensitive LIF
      detection with excitation and emission wavelengths at 635 nm and 685 nm,
      respectively, and at the same time, the overall charge was converted to positive.
      Electrolyte pH and concentration of polyethylene oxide (PEO) significantly
      affected the resolution of the microorganisms. Their optimal separation in the 14
      mm separation channel was achieved in less than 30 s (R(s) > 5.3) in an
      electrolyte consisting of 3.94 mM Tris, 0.56 mM boric acid, 0.013 mM
      ethylenediaminetetraacetic acid disodium salt dihydrate (pH 10.5), and 0.025%
      PEO, with injection/separation voltages of +1000/+1000 V. The separation
      mechanism is likely employing contributions to the overall cationic charge from
      both the prevalently anionic membrane proteins and the cationic NB. Importantly,
      the resulting cationic NB-stained cells exhibited excellent separation
      selectivity and efficiency of ~38000 theoretical plates for rapid separations
      within 30-40 s. The results indicate the potential of chip-CE for microbial
      analysis, which offers separations of a wide range of species with high
      efficiency, sensitivity, and throughput.

PMID- 22648809
TI  - Divergent dispersion behavior of ssDNA fragments during microchip electrophoresis
      in pDMA and LPA entangled polymer networks.
AB  - Resolution of DNA fragments separated by electrophoresis in polymer solutions
      ("matrices") is determined by both the spacing between peaks and the width of the
      peaks. Prior research on the development of high-performance separation matrices
      has been focused primarily on optimizing DNA mobility and matrix selectivity, and
      gave less attention to peak broadening. Quantitative data are rare for peak
      broadening in systems in which high electric field strengths are used (>150
      V/cm), which is surprising since capillary and microchip-based systems commonly
      run at these field strengths. Here, we report results for a study of band
      broadening behavior for ssDNA fragments on a glass microfluidic chip, for
      electric field strengths up to 320 V/cm. We compare dispersion coefficients
      obtained in a poly(N,N-dimethylacrylamide) (pDMA) separation matrix that was
      developed for chip-based DNA sequencing with a commercially available linear
      polyacrylamide (LPA) matrix commonly used in capillaries. Much larger DNA
      dispersion coefficients were measured in the LPA matrix as compared to the pDMA
      matrix, and the dependence of dispersion coefficient on DNA size and electric
      field strength were found to differ quite starkly in the two matrices. These
      observations lead us to propose that DNA migration mechanisms differ
      substantially in our custom pDMA matrix compared to the commercially available
      LPA matrix. We discuss the implications of these results in terms of developing
      optimal matrices for specific separation (microchip or capillary) platforms.

PMID- 22648811
TI  - Isotachophoretic purification of nanoparticles: tuning optical properties of
      quantum dots.
AB  - Synthesized nanoparticles often require fine fractionation according to shape,
      dimension, mass, chemical composition, charge, and other properties in order to
      become suitable for practical use. Quantum dots (QDs) are luminescent
      nanocrystals with narrow emission peaks. This property has been widely utilized
      for the multiplexed sensing and barcoding of microparticles. QDs with narrower
      emission peaks are preferred for such applications. The width of the emission
      peaks can be significantly reduced after purification. A newly developed
      preparative isotachophoretic method employs the dependence of spectral properties
      and electrophoretic mobility on the diameter of QDs. Separated fractions of QDs
      revealed narrower emission peaks (72% of the original width) and improved quantum
      yield (two-fold). The usefulness of the developed isotachophoresis for
      purification and analysis of other nanostructures, for example, plasmonic
      nanoparticles and nanobioconjugates, is expected, too.

PMID- 22648813
TI  - Large volume sample stacking with EOF and sweeping in CE for determination of
      common preservatives in cosmetic products by chemometric experimental design.
AB  - This study proposes a capillary electrophoresis method incorporating large volume
      sample stacking, EOF and sweeping for detection of common preservatives used in
      cosmetic products. The method was developed using chemometric experimental design
      (fractional factorial design and central composite design) to determine multiple
      separation variables by efficient steps. The samples were loaded by hydrodynamic
      injection (10 psi, 90 s), and separated by phosphate buffer (50 mM, pH 3)
      containing 30% methanol and 80 mM SDS at -20 kV. During method validation,
      calibration curves were found to be linear over a range of 5-100 MUg/mL for butyl
      paraben and isobutyl paraben; 0.05-10 MUg/mL for ethyl paraben; 0.2-50 MUg/mL for
      dehydroacetic acid; 0.5-70 MUg/mL for methyl paraben; 5-350 MUg/mL for sorbic
      acid; 0.02-450 MUg/mL for p-hydroxybenzoic acid and 0.05-10 MUg/mL for salicylic
      acid and benzoic acid. The analytes were analysed simultaneously and their
      detection limits (S/N = 3) were down to 0.005-2 MUg/mL. The analysis method was
      successfully used for detection of preservatives used in commercial cosmetics.

PMID- 22648812
TI  - Investigation of neutral monolithic capillary columns with varying n-alkyl chain
      lengths in capillary electrochromatography.
AB  - Two different neutral nonpolar monolithic columns series (designated as A and B
      columns series) each consisting of three columns at varying n-alkyl chain length
      were prepared by the copolymerization of the functional monomers C8-methacrylate,
      C12-acrylate, or C16-methacrylate with the cross-linking monomer pentaerythritol
      triacrylate (PETA) to yield monoliths with surface bound C8, C12, and C16 chains.
      In the A columns series, the composition of the functional monomers and
      crosslinker was adjusted to yield comparable chromatographic retention regardless
      of the alkyl chain length. In the B columns series, the composition of the
      functional monomers and crosslinker was kept constant yielding chromatographic
      retention, which increased as expected in the order of increasing the n-alkyl
      chain length. Due to their direct influences on the monolith porosity and
      retention energetic, the nature and composition of the monomers at a given
      porogen composition have largely affected the solute's mass transfer
      characteristics and sorption kinetics, as assessed by the van Deemter plots and
      separation efficiencies. The C16-monolith of the A series yielded the highest
      separation efficiency toward small solutes, but the A columns series were
      inadequate for protein separation. The C8-monolith of the B series provided the
      best separation efficiency for proteins while for tryptic peptide mapping, the
      C16-monolith of the A series seems to provide the best separation. For large
      protein molecules, the energetically "softer" C8 surface allowed faster sorption
      kinetics and in turn improved efficiency, while an energetically "harder" C16
      surface favored better separation of the smaller size peptide solutes.

PMID- 22648814
TI  - Dispersive liquid-liquid microextraction of pesticides and metabolites from soils
      using 1,3-dipentylimidazolium hexafluorophosphate ionic liquid as an alternative
      extraction solvent.
AB  - In this work, the use of the ionic liquid (IL) 1,3-dipentylimidazolium
      hexafluorophosphate ([PPIm][PF6]) as an alternative extractant for IL dispersive
      liquid-liquid microextraction (IL-DLLME) of a group of pesticides and metabolites
      (2-aminobenzimidazole, carbendazim/benomyl, thiabendazole, fuberidazole,
      carbaryl, 1-naphthol, and triazophos) from soils is described. After performing
      an initial ultrasound-assisted extraction (USE), the IL-DLLME procedure was
      applied for the extraction of these organic analytes from soil extracts.
      Separation and quantification was achieved by high-performance liquid
      chromatography (HPLC) with fluorescence detection (FD). Calibration, precision,
      and accuracy of the described USE-IL-DLLME-HPLC-FD method using [PPIm][PF6] as an
      alternative extractant was evaluated with two soils of different physicochemical
      properties. Accuracy percentages were in the range 93-118% with RSD values below
      20%. A comparison of the performance of [PPIm][PF6] versus that of the so-common
      1-hexyl-3-methylimidazolium hexafluorophosphate ([HMIm][PF6]) was accomplished.
      Results indicate a comparable extraction efficiency with both ILs, being slightly
      higher with [HMIm][PF6] for the metabolite 2-aminobenzimidazole, and slightly
      higher with [PPIm][PF6] for triazophos. In all cases, LODs were in the low ng/g
      range (0.02-14.2 ng/g for [HMIm][PF6] and 0.02-60.5 ng/g for [PPIm][PF6]). As a
      result, the current work constitutes a starting point for the use of the IL
      [PPIm][PF6] for further analytical approaches.

PMID- 22648815
TI  - Chiral recognition of imperanene enantiomers by various cyclodextrins: a
      capillary electrophoresis and NMR spectroscopy study.
AB  - The enantiomers of imperanene, a novel polyphenolic compound of Imperata
      cylindrica (L.), were separated via cyclodextrin-modified capillary
      electrophoresis. The anionic form of the analyte at pH 9.0 was subject to
      complexation and enantioseparation CE studies with neutral and charged
      cyclodextrins. As chiral selectors 27 CDs were applied differing in cavity size,
      sidechain, degree of substitution (DS) and charge. Three hydroxypropylated and
      three sulfoalkylated CD preparations provided enantioseparation and the migration
      order was successfully interpreted in each case in terms of complex mobilities
      and stability constants. The best enantioresolution (R(S)  = 1.26) was achieved
      using sulfobutyl-ether-gamma-CD (DS ~4), but it could be enhanced by extensive
      investigations on dual selector systems. After optimization (CD concentrations
      and pH) R(S)  = 4.47 was achieved using a 12.5 mM sulfobutyl-ether-gamma-CD and
      10 mM 6-monodeoxy-6-mono-(3-hydroxy)-propylamino-beta-cyclodextrin dual system.
      The average stoichiometry of the complex was determined with Job's method using
      NMR-titration and resulted in a 1:1 complex for both (2-hydroxy)propyl-beta- and
      sulfobutyl-ether-gamma-CD. Further NMR experiments suggest that the coniferyl
      moiety of imperanene is involved in the host-guest interaction.

PMID- 22648816
TI  - Cocaine detection by structure-switch aptamer-based capillary zone
      electrophoresis.
AB  - Aptamers, which are nucleic acid oligonucleotides that can bind targets with high
      affinity and specificity, have been widely applied as affinity probes in
      capillary electrophoresis (CE). Due to relative weak interaction between aptamers
      and small molecules, the application of aptamer-based CE is still limited in
      certain compounds. A new strategy that is based on the aptamer structure-switch
      concept was designed for small molecule detection by a novel CE method. A
      carboxyfluorescein (fluorescein amidite, FAM) label DNA aptamer was first
      incubated with partial complementary strand (CS), and then the free aptamer and
      the aptamer-CS duplex were well separated and determined by metal cation mediated
      CE/laser-induced fluorescence. When the target was introduced into the incubated
      sample, the hybridized form was destabilized, resulting in the changes of the
      fluorescence intensities of the free aptamer and the aptamer-CS duplex. The
      length of CS was investigated and 12 mer CS showed the best sensitivity for the
      detection of cocaine. The presented CE-LIF method, which combines the separation
      power of CE with the specificity of interactions occurring between target,
      aptamer, and CS, could be a universal detection strategy for other aptamer
      specified small molecules.

PMID- 22648817
TI  - Determination of metolcarb in food by capillary electrophoresis immunoassay with
      a laser-induced fluorescence detector.
AB  - A capillary electrophoresis immunoassay (CEIA) was developed for the
      determination of trace metolcarb (MTMC) in food. The method was based on the
      competitive reactions between fluorescently labeled MTMC tracer and free MTMC
      with a limited amount of anti-MTMC antibody and the separation and determination
      by CE with LIF detector. A fluorescent reagent, FITC was labeled on MTMC to
      construct an immunofluorescent probe. CEIA experimental parameters such as the pH
      value and concentration of the running buffer and separation voltage as well as
      incubation time were systematically investigated. Under the optimized conditions,
      fluorescently labeled antigen and antibody bound could be well separated within 3
      min using Na2B4O7/NaH2PO4 buffer (20:10 mmol/L, pH 9.0) for background
      electrolyte, 20 kV for the separation voltage, and 20 degrees C for the column
      temperature. The linear range of the method was 0.25-50.0 MUg/L with LOD 0.07
      MUg/L. The RSD for relative migration time and relative fluorescence intensity
      ratio were 2.90% (intraday) and 4.73% (intraday), respectively. The proposed
      method has been applied to determine the residue of MTMC in food samples with the
      satisfactory recovery.

PMID- 22648818
TI  - Multiplex quantitative foodborne pathogen detection using high resolution CE-SSCP
      coupled stuffer-free multiplex ligation-dependent probe amplification.
AB  - Sensitive multiplex detection methods for foodborne pathogens are important in
      controlling food safety, and detection of genetic markers is accepted to be one
      of the best tools for sensitive detection. Although CE technology offers great
      potential in terms of sensitive multiplex detection, the necessary amplification
      is confined to markers sharing common primers such as the 16S rRNA gene. For
      precise and sensitive detection, pathogen-specific genes are optimal markers.
      Although multiplex ligation-dependent probe amplification (MLPA) is appropriate
      for amplification of specific markers, the requirement for stuffers, to ensure
      length-dependent separation on CE, is a major obstacle in detection of foodborne
      pathogens. In the present study, we developed stuffer-free MLPA using high
      resolution CE-SSCP to sensitively detect ten foodborne pathogens. The probe set
      for MLPA prior to CE-SSCP analysis was designed for species-specific detection.
      After careful optimization of each MLPA step, to ensure that CE-SSCP analysis was
      informative, we found that all ten pathogens could be reliably identified; the
      limits of detection were 0.5-5 pg of genomic DNA, and more than 100-fold increase
      could be quantitatively determined. Thus, MLPA-CE-SSCP is a sensitive and
      reliable technique for pathogen detection.

PMID- 22648819
TI  - Complexation of europium and uranium by humic acids analyzed by capillary
      electrophoresis-inductively coupled plasma mass spectrometry.
AB  - Investigations of the mobility of radioactive and nonradioactive substances in
      the environment are important tasks for the development of a future disposal in
      deep geological formations. Dissolved organic matter (DOM) can play an important
      role in the mobilization of metal ions due to complexation. In this study, we
      investigate the complexation behavior of humic acid (HA) as a model substance for
      DOM and its influence on the migration of europium as homologue for the actinide
      americium and uranium as the principal component of nuclear fuel. As speciation
      technique, capillary electrophoresis (CE) was hyphenated with inductively coupled
      plasma mass spectrometry (ICP-MS). For the study, 0.5 mg.L-1 of the metals and 25
      mg.L-1 of (purified Aldrich) HA and an aqueous solution sodium-perchlorate with
      an ionic strength of 10 mM at pH 5 were used. CE-ICP-MS clearly shows the
      different speciation of the triple positively charged europium and the double
      positively charged uranyl cation with HA.

PMID- 22648820
TI  - Strategies for excluding false Y-chromosomal SNP entries from human genome
      databases.
AB  - Current human genome databases for public single nucleotide polymorphisms (SNPs)
      still contain a substantial fraction of false entries. The main reasons for
      errors include sequencing or assembly errors, paralogous sequence-, and private
      variants. In the course of our studies on the Y chromosome, we established a set
      of internal laboratory guidelines for reliably identifying false SNP entries in
      databases.

PMID- 22648826
TI  - Generation of mature hematopoietic cells from human pluripotent stem cells.
AB  - A number of malignant and non-malignant hematological disorders are associated
      with the abnormal production of mature blood cells or primitive hematopoietic
      precursors. Their capacity for continuous self-renewal without loss of
      pluripotency and the ability to differentiate into adult cell types from all
      three primitive germ layers make human embryonic stem cells and induced
      pluripotent stem cells (hiPSCs) attractive complementary cell sources for large
      scale production of transfusable mature blood cell components in cell replacement
      therapies. The generation of patient-specific hematopoietic stem/precursor cells
      from iPSCs by the regulated manipulation of various factors involved in
      reprograming to ensure complete pluripotency, and developing innovative
      differentiation strategies for generating unlimited supply of clinically safe,
      transplantable, HLA-matched cells from hiPSCs to outnumber the inadequate source
      of hematopoietic stem cells obtained from cord blood, bone marrow and peripheral
      blood, would have a major impact on the field of regenerative and personalized
      medicine leading to translation of these results from bench to bedside.

PMID- 22648828
TI  - [Pay attention to the nutritional problems in patients with gastrointestinal
      dysfunction].
AB  - Gut dysfunction is defined as the impairment of intestinal parenchyma and(or)
      intestinal function leading to dyspepsia, malabsorption, and(or) intestinal
      barrier dysfunction. In the stress state, gastrointestinal tract contributes to
      the physiopathological change, which is considered as the "central organ after
      stress". Because of ischemia, anoxia and metabolic disturbance, critical illness
      is frequently complicated with intestinal dysfunction, which is one of the
      difficulties to treat critically ill patients. Undoubtedly, nutritional support
      is one of the indispensable therapies of intestinal dysfunction, which is also
      difficult to manage. This report was aimed to elaborate the definition, causes of
      intestinal dysfunction, assessment of nutritional status, and design of
      nutritional support in these patients.

PMID- 22648827
TI  - Generation of red blood cells from human embryonic/induced pluripotent stem cells
      for blood transfusion.
AB  - Red blood cell (RBC) transfusion is necessary for many patients with emergency or
      hematological disorders. However, to date the supply of RBCs remains labile and
      dependent on voluntary donations. In addition, the transmission of infectious
      disease via blood transfusion from unspecified donors remains a risk.
      Establishing a large quantity of safe RBCs would help to address this issue.
      Human embryonic stem (hES) cells and the recently established human induced
      pluripotent stem (hiPS) cells represent potentially unlimited sources of donor
      free RBCs for blood transfusion, as they can proliferate indefinitely in vitro.
      Extensive research has been done to efficiently generate transfusable RBCs from
      hES/iPS cells. Nevertheless, a number of challenges must be overcome before the
      clinical usage of hES/iPS cell-derived RBCs can become a reality.

PMID- 22648829
TI  - [Make efforts to improve overall levels of clinical nutriology in China].
AB  - Clinicians should assume the responsibility of nutritional therapy for
      satisfactory outcomes. They should master knowledge on nutritional metabolism,
      and participate in the administration of nutritional support. Clinicians should
      be acquainted with new concepts and standardized techniques in this field, such
      as different requirement of energy, understanding of early nutritional support,
      and optimal regimens of enteral or parenteral nutrition.

PMID- 22648830
TI  - [Assessment of nutritional status and selection of nutritional support route in
      patients undergoing gastrointestinal surgery].
AB  - Nutritional risk and malnutrition was significantly higher in patients undergoing
      gastrointestinal surgery as compared to patients in other surgical departments,
      especially in elder patients, which would directly impact on the efficacy, cost
      and prognosis. Nutritional screening and assessment should be performed within 24
      48 hours after admission. Patients at high risk of malnutrition should be planned
      with early nutrition support. The best nutrition route should be determined to
      improve the outcomes of surgery and nutritional support, reduce the
      complications, length of hospital stay and healthcare costs, and improve the
      quality of life in patients.

PMID- 22648832
TI  - [Choice of nutritional plans for patients with gastrointestinal neoplasms].
AB  - Malnutrition is the common complication for patients with gastrointestinal
      neoplasms. Nutrition therapy is the key and first step, but there are some
      uncertain questions in the clinical practices. We will discuss some experiences
      on selecting nutrition plans for patients with gastrointestinal neoplasms.

PMID- 22648833
TI  - [Effects of nutritional support on the hypermetabolism of patients with digestive
      tract fistula].
AB  - Digestive tract fistulas are abnormal connections between gastrointestinal tract
      and other organs that most commonly occur after surgery. Morbidity and mortality
      associated with postoperative fistulas are substantial as they are highly
      associated with nutritional deficits, hypermetabolism, septic complications and
      concomitant diseases that may appear during prolonged hospital stay. Digestive
      tract fistula is a challenging condition that involves a multidisciplinary
      approach to management. The main treatment includes intestinal rest,correction of
      electrolytic disturbances, parenteral nutrition,protection of the skin
      surrounding the fistula, and treatment and prophylaxis of any related local or
      systemic septic complications. Nutritional support, which is an effective and
      promising treatment for patients with digestive tract fistulas, can promote the
      closure of the fistula and decrease the duration of hospital stay.

PMID- 22648831
TI  - [Application of specific nutrients for patients after surgery].
AB  - Special nutritional support containing glutamine, arginine, and omega-3 fatty
      acids has therapeutic and immunomodulatory effects, and can significantly reduce
      the incidence of postoperative infectious complications and length of hospital
      stay in surgical patients. This review provides a clinical update regarding the
      concept and the use of pharmaconutrition and immunonutrition in patients
      undergoing gastrointestinal surgery.

PMID- 22648834
TI  - [Application of enteral nutrition tube placement and feeding equipment].
AB  - Although considerable clinical problems were solved by parenteral nutrition since
      1960s, because of the risk of infectious and metabolic complications and advance
      in feeding tube placement, feeding methods, and artificial ingredient nutrients,
      enteral nutrition from 400 years ago has been brought to attention again. This
      review article is aimed to illustrate the issues related to enteral tube feeding
      in esophageal surgery.

PMID- 22648835
TI  - [Establishment and maintenance of the way of enteral nutrition support].
AB  - Enteral nutrition is the preferred way of clinical nutrition support, especially
      in critical ill patients. Establishment and maintenance of an appropriate way
      should be considered to ensure the safety and effectiveness of enteral nutrition
      support.

PMID- 22648836
TI  - [Influence of Lipoplus fat emulsion on postoperative nutritional status and early
      inflammatory response in patients with gastrointestinal malignancies].
AB  - OBJECTIVE: To investigate the effect of Lipoplus on postoperative nutritional
      status and inflammatory response in patients with gastrointestinal malignancies.
      METHODS: Sixty-four patients with gastrointestinal malignancies were randomized
      using random digit table to receive isonitrogenous, isocaloric total parenteral
      nutrition for 5 days including either Lipoplus or Lipofundin with 32 patients in
      each group. Blood samples were obtained before the surgery, postoperative days 1,
      2, 3, and 6 to evaluate the nutritional status(prealbumin, retinol binding
      protein, and nitrogen balance) and inflammatory response [C-reaction
      protein(CRP), and leukotriene(LTB) 5, LTB4]. The incidence of postoperative
      systemic inflammatory response syndrome(SIRS), infection, postoperative
      complications, mortality, APACHEII score, length of hospital stay and other
      clinical indicators were recorded. RESULTS: On postoperative day 1, prealbumin
      and retinol binding protein were significantly lower as compared to preoperative
      levels. These parameters increased significantly(P<0.05) on postoperative day 6
      and the nitrogen balance was positive. On postoperative day 6, CRP was
      significantly lower in both groups as compared to postoperative day 3 (P<0.05),
      and the decrease was more prominent in Lipoplus than Lipofundin(P<0.05). There
      was a significant increase in LTB5/LTB4 as compared to postoperative day
      1(P<0.05) in the Lipoplus group, however the increase was not statistically
      significant in the Lipofundin group(P>0.05). The incidence of postoperative
      infection was significantly lower in the Lipoplus group(3.1% vs. 6.3%, P<0.05),
      as was that of SIRS(9.4% vs. 15.6%, P<0.05). The APACHEII score was higher in the
      Lipoplus group but the difference was not statistically significant(3.6+/-2.0 vs.
      3.3+/-2.1, P>0.05). The length of hospital stay was significantly shorter in
      Lipoplus group[(6.4+/-1.1) d vs. (8.2+/-1.3) d, P<0.05]. CONCLUSION: Lipoplus can
      improve the postoperative nutritional status and minimize the inflammatory
      response in patients with gastrointestinal malignancies.

PMID- 22648837
TI  - [Use of fish oil lipid emulsion in patients undergoing major surgery and those
      with systemic inflammatory response syndrome: a cost-effectiveness analysis].
AB  - OBJECTIVE: To investigate the cost-effectiveness of fish oil in patients
      undergoing major surgery and those with systemic inflammatory response
      syndrome(SIRS). METHODS: A retrospective study was conducted in patients
      undergoing major surgery and those with SIRS on admission in the Zhongshan
      Hospital from January 2008 to December 2011. Fish oil group was enrolled and
      matched to control group by 1:2 for gender, age, diagnosis, and surgical
      procedure. There were 220 pairs of patients who were not admitted to ICU, 102
      pairs of patients admitted to ICU, and 66 pairs of patients with SIRS. The
      clinical outcomes and costs were measured and cost-effectiveness analyses were
      conducted. RESULTS: The clinical outcomes and costs showed no significant
      difference between the fish oil group and the control group in those patients who
      were not admitted to ICU(P>0.05). Fish oil fat emulsion supplementation
      significantly reduced the length of total hospital stay, postoperative hospital
      stay, ICU stay, re-operation rate, infection rates, perioperative mortality in
      patients admitted to ICU and those with SIRS(P<0.05). The cost-effectiveness
      ratio of non-reoperation rate, non-infection rate, and survival rate were lower
      in those patients receiving fish oil fat emulsion as compared with those without
      fish oil administration. Fish oil fat emulsion supplementation could reduce cost
      effectiveness ratios of non-reoperation rate, non-infection rate and survival
      rate by 105 RMB, 160 RMB, and 89 RMB respectively in major surgical patients who
      admitted to ICU, and by 670 RMB, 280 RMB, and 220 RMB respectively in SIRS
      patients. CONCLUSIONS: Addition of fish oil fat emulsion to clinical nutrition
      may have positive effects on critically ill patients. It seems that the effects
      of fish oil fat are strongly related to the severity of patient's underlying
      disease. Fish oil fat emulsion supplementation shows acceptable cost
      effectiveness ratio and pharmacoeconomic value.

PMID- 22648838
TI  - [Comparison of nutritional status between pancreaticojejunostomy and
      pancreaticogastrostomy following pancreaticoduodenectomy].
AB  - OBJECTIVE: To compare the nutritional status between pancreaticojejunostomy(PJ)
      and pancreaticogastrostomy(PG) following pancreaticoduodenectomy. METHODS: A
      retrospective clinical analysis was performed on 37 patients undergoing
      pancreaticoduodenectomy(PD) for duodenal carcinoma and pancreatic non-epithelial
      tumor with PG(n=19) and PJ(n=18) in the First Hospital of Sun Yat-sen University
      from April 2006 to December 2010. All the patients had a needle catheter
      jejunostomy inserted at the conclusion of laparotomy. Postoperative early enteral
      nutrition and parenteral nutrition was performed for all the patients.
      Nutritional status of two groups was compared in body mass index (BMI), serum
      nutritional parameters such as albumin, transferrin and prealbumin before surgery
      and on 1, 3, and 6 months postoperatively. RESULTS: There were no significant
      differences between PG and PJ groups in operative time, blood loss, pancreatic
      fistula, perioperative death, or postoperative length of hospital stay. One month
      after surgery, there were no significant differences in BMI [(17.1+/-7.0) vs.
      (19.0+/-4.8) kg/m(2), P>0.05], albumin [(30.1+/-0.5) vs. (32.1+/-1.3) g/L,
      P>0.05], transferrin [(1.89+/-0.57) vs. (2.01+/-0.61) g/L, P>0.05] and
      prealbumin[(0.18+/-0.05) vs. (0.18+/-0.09) g/L, P>0.05]. These parameters were
      decreased at 1 month after surgery, and gradually recovered to baseline or higher
      than the preoperative levels at 6 months after surgery. However, the differences
      were still not statistically significant between two groups. CONCLUSIONS: The
      influence of PJ and PG on the postoperative nutritional status are comparable.

PMID- 22648839
TI  - [Nutritional risk screening and nutrition assessment for gastrointestinal cancer
      patients].
AB  - OBJECTIVE: To investigate the nutritional status, and provide evidence for
      nutritional treatment option. METHODS: A total of 452 patients with
      gastrointestinal cancer were selected, including 156 gastric cancer,117 colon
      cancer, and 180 rectal cancer. The nutritional risk screening 2002(NRS2002) was
      applied to grade the nutritional risk. A multi-frequency bioelectrical impedance
      analysis was used to measure the patients' body composition. Albumin (Alb),
      prealbumin(PA), transferring(Tf), retinol binding protein(RBP), red blood
      cell(RBC), hemoglobin (Hb), haematocrit(Hct) were measured after fasting.
      RESULTS: The rate of patients with NRS2002 score more than 3 was 70.5%(110/156)
      for gastric cancer, 53.8%(63/117) for colon cancer, and 46.7%(86/180) for rectal
      cancer. The score for impaired nutritional status more than 1 for gastric cancer
      was higher than that for colorectal cancer(P<0.05), while patients with disease
      score more than 2 was less for gastric cancer(P<0.05). Body mass index(BMI),
      obesity degree, fat content, fat percentage, and arm circumference were lower in
      gastric cancer patients as compared to  colorectal cancer patients(P<0.05); but
      protein percentage, muscle percentage, ratio of muscles of arm, and cell mass
      percentage were higher in gastric cancer patients(P<0.05). The proportions of
      patients with low Alb, PA, Tf, BC, Hb, Hct were higher for gastric cancer and
      colon cancer(P<0.05). CONCLUSION: Patients with gastric cancer are prone to fat
      loss and therefore have a higher nutritional risk and malnutrition than those
      with colorectal cancer. Combination of body composition analysis and laboratory
      examination may achieve comprehensive evaluation of the nutritional status of
      patients, and provide the evidence of nutritional therapy by being combined with
      NRS2002 score.

PMID- 22648840
TI  - [Effect of early oral enteral nutrition on clinical outcomes after gastric cancer
      surgery].
AB  - OBJECTIVE: To investigate the effect of early oral feeding with enteral nutrition
      preparation after surgery on clinical outcomes in patients with gastric cancer.
      METHODS: Sixty patients with gastric cancer undergoing radical operation between
      July 2010 and May 2011 were randomly divided into two groups using random digit
      table: experimental group(n=30, administration of water and enteral nutrition
      early after surgery) and control group(n=30, conventional postoperative care
      protocol). Clinical outcomes, immune function, and nutritional status between the
      two groups were compared. RESULTS: As compared to the control group, duration of
      fever was significantly shorter in the experimental group [(81.1+/-6.4) h vs.
      (87.3+/-8.0) h, P<0.05], as were postoperative time of flatus [(79.9+/-9.5) h vs.
      (86.6+/-8.7) h, P<0.05] and postoperative hospital stay [(7.83+/-2.23) d vs.
      (9.57+/-1.96) d, P<0.01]. The medical cost [(30,220+/-3,220) RMB vs.(34,600+/
      32,120) RMB, P<0.01] was lower than that in the control group. There was no
      significant difference in morbidity between the two groups[13.3%(4/30) vs.
      16.7%(5/30), P>0.05]. The levels of CD3(+)T, CD4(+)T, NK cell, CD4(+)T/CD8(+)T,
      albumin, and prealbumin were higher in the experimental group as compared to the
      control group on postoperative day 3 and 7(P<0.05). CONCLUSION: Early oral
      feeding with enteral nutrition preparation after surgery can improve the
      nutritional status and immune function, and accelerate the rehabilitation for
      patients with gastric cancer.

PMID- 22648841
TI  - [Effect of intraoperative intraperitoneal chemotherapy and postoperative
      nutritional support on intestinal permeability and cellular immune function in
      patients with advanced gastric cancer].
AB  - OBJECTIVE: To investigate the effect of hyperthermic intraoperative
      intraperitoneal chemotherapy(HIIC) and postoperative nutritional support on the
      intestinal permeability and the cellular immunity function in patients with
      advanced gastric cancer. METHODS: All the patients diagnosed as advanced gastric
      cancer in the Gastric Tumor Diagnosis and Treatment Center of Jiangsu Cancer
      Hospital were randomly divided into three groups using random digit table:(1)EN
      group treated with enteral nutrition during postoperative period; (2)HIIC+EN
      group treated with HIIC combined with postoperative enteral nutrition;(3)HIIC+PN
      group treated with HIIC combined with postoperative parenteral nutrition. Index
      of lactulose/mannitol(L/M) ratio was used to evaluate the permeability of
      intestinal mucosa. The percentage of CD4(+), CD8(+) and NK cell, the ratio of
      CD4/CD8 T cell in peripheral blood were tested by flow cytometry. The time points
      of these measurements were the day before surgery, postoperative days (POD) 3, 7,
      and 12. RESULTS: Compared with the day before surgery(POD-1), the ratio of L/M on
      POD+3 increased significantly in all the three groups(0.1235+/-0.0611 vs.
      0.0280+/-0.0183, 0.1648+/-0.0571 vs. 0.0305+/-0.0208, 0.1702+/-0.0628 vs.
      0.0298+/-0.0229)(P<0.05) and then decreased gradually. The L/M ratio of
      EN(0.0278+/-0.0217) and HIIC+EN(0.0336+/-0.0235) groups recovered to the baseline
      on POD+12, however HIIC+PN group still had elevated L/M ratio(0.0616+/-0.0430).
      The percentage of CD4(+)T cell and the ratio of CD4/CD8 in HIIC+EN group and
      HIIC+PN group were significantly lower than those in EN group(P=0.033, P=0.002,
      respectively). Compared with the POD-1,the percentage of CD4(+)T cell and the
      ratio of CD4/CD8 in HIIC+EN group and EN group on POD+12 were increased
      significantly(P<0.05). CONCLUSIONS: HIIC may cause significant increase in
      intestinal permeability and inhibit cellular immunity in patients undergoing
      radical resection for advanced gastric cancer. Mucosal permeability can be
      reversed by enteral nutrition.

PMID- 22648842
TI  - [Study of different enteral nutrition formulation treatment after esophagectomy].
AB  - OBJECTIVE: To compare the efficiency of different early enteral nutrition (EN)
      with Ensure, Nutrison, and Peptison in postoperative patients with esophageal
      carcinoma. METHODS: A total of 45 postoperative patients with esophageal
      carcinoma were randomly divided into three groups using random digit table:
      Ensure group (n=15), Nutrition group (n=15), and Peptison group (n=15). Enteral
      nutrition was given using nasogastric tube from the 2nd postoperative day for 8
      days. Albumin and prealbumin were detected on the day before surgery and
      postoperative day 9 after fasting. The time to gastrointestinal tract function
      recovery, complications, and the cost of enteral nutrition were compared among
      the three groups. RESULTS: There were no significant differences in postoperative
      nutrition indices(albumin and prealbumin) and EN-related complications among the
      three groups(all P>0.05). The time to gastrointestinal tract function recovery in
      Ensure group [(52.4+/-15.7) h] and Nutrison group [(50.8+/-12.4) h] was less than
      that in Peptison group [(60.3+/-16.8) h] (P<0.05). The expense of Ensure group
      [(443.3+/-45.8) RMB] was obviously less than that of Nutrison group[(639.5+/
      52.6) RMB] and Peptison group [(990.5+/-95.5) RMB](both P<0.01). CONCLUSIONS:
      Ensure, Nutrison and Peptison can be used for postoperative early enteral
      nutrition in patients with esophageal carcinoma, and the efficacy and
      complication are comparable. The cost of Ensure is the lowest.

PMID- 22648843
TI  - [Application of microbiological and immunological enteral nutrition in patients
      with gastrointestinal cancer complicated with diabetes mellitus].
AB  - OBJECTIVE: To investigate the effects of microbiological and immunological
      enteral nutrition using composition of probiotics, glutamine, fish oil, and
      peptisorb on patients with gastrointestinal cancer complicated with diabetes
      mellitus. METHODS: From January 2007 to October 2010, 67 patients with
      gastrointestinal cancer complicated with diabetes mellitus were admitted to the
      Liaocheng People's Hospital of Shandong Province and were randomized into the
      treatment group(n=33, enteral nutrition with probiotics, glutamine, and fish oil)
      and the routine group(n=34, regular enteral nutrition). Fasting blood
      glucose(FBG), insulin(FINS), number of lymphocytes(including CD3(+)T cell,
      CD4(+)T cell, CD8(+)T cell, CD4(+)/CD8(+)) and natural killer (NK) cells of the
      two groups were detected on the day before surgery and postoperative day 3 and 7.
      Insulin resistance index (InHOMA-IR) was calculated by using the homeostasis
      model assessment(HOMA). The incidence of nosocomial infections and intestinal
      function recovery time, and length of hospital stay were collected. RESULTS: On
      postoperative day 7, FINS[(8.4+/-3.7) mU/L vs. (13.7+/-5.4) mU/L, P<0.05] and
      InHOMA-IR(1.11+/-0.23 vs. 1.68+/-0.39, P<0.05) were lower in the treatment group
      than that in the routine group. The number of CD4(+)[(45.2+/-5.4)% vs. (38.1+/
      2.9)%, P<0.05], CD4/CD8 (2.05+/-0.27 vs. 1.58+/-0.16, P<0.05), and NK cells
      [(19.5+/-6.6)% vs. (15.4+/-5.6)%, P<0.05] were higher in the treatment group.
      There were no significant differences in nosocomial infection [6.1%(2/33) vs.
      17.6%(6/34), P>0.05] and intestinal function recovery time[(69.3+/-9.5) h vs.
      (70.1+/-11.6) h, P>0.05] between the two groups. However, the length of hospital
      stay [(17+/-3.8) d vs. (21+/-4.2) d, P<0.05] was significantly shorter in the
      treatment group. CONCLUSION: For patients with gastrointestinal cancer
      complicated with diabetes mellitus, microbiota enteral nutrition can reduce
      insulin resistance, improve the immune status, and promote postoperative
      recovery.

PMID- 22648844
TI  - [Long-term outcomes and nutrition evaluation in children with total colonic
      aganglionosis].
AB  - OBJECTIVE: To examine the long-term outcomes of total colonic aganglionosis (TCA)
      and to evaluate their nutritional status. METHODS: Eleven pediatric patients
      treated for TCA between January 1999 and December 2010 were included in the study
      and followed up. Physical measurements including height, weight and laboratory
      tests were assessed. Anorectal functions were evaluated with Kelly score and
      quality of life(QOL) using questionnaire. RESULTS: The length of follow-up ranged
      from 8 to 147 months. The children had satisfactory anorectal function (Kelly
      score, 5-6). One child had a Kelly score of 3. The children who were followed up
      less than 48 months had significant higher Kelly scores compared with those with
      more than 48 months follow-up(P<0.05). QOL was good in nine patients (QOL score,
      9-10) and moderate (score, 7-8) in 2 patients. Weight-for-age was normal in 2
      patients, mild malnutrition in 6 patients, and moderate malnutrition in 3
      patients. Height-for-age was normal in 6 patients, mild malnutrition in 3
      patients, and moderate malnutrition in 2 patients. The serum albumin was(49.0+/
      2.7) g/L in children with well-educated parents, significantly higher than those
      with poorly-educated parents(44.3+/-1.9) g/L(P<0.05). CONCLUSIONS: Long-term
      outcomes of children with TCA are satisfactory with good anorectal function and
      quality of life. Low body weight is more common than low height.  Children with
      well-educated parents have better nutrition status.

PMID- 22648845
TI  - [Effect of n-3 polyunsaturated fatty acids on proliferation and apoptosis of
      human colon cancer cell].
AB  - OBJECTIVE: To investigate the effects of n-3 polyunsaturated fatty acids(n-3PUFA)
      on human colorectal cancer cell line HT-29 and associated mechanism. METHODS: The
      effects of docosahexaenoic acid (DHA) on the proliferation and apoptosis on HT-29
      human colorectal cancer cells were evaluated by MTT assay, cell morphology
      (Hoechst33258 dyeing), DNA gel electrophoresis, and flow cytometry. The content
      of n-6PUFA and n-3PUFA of the treated cells and the ratio of n-6/n-3PUFA were
      analyzed by chromatography. RESULTS: DHA effectively inhibited HT-29 cell
      proliferation in a dose- and time-dependent manner. The proliferative inhibition
      rates of HT-29 cells treated with 10, 20, 40, and 80 mg/L DHA for 24 hours were
      16.8%, 24.7%, 50.0%, and 60.1%, respectively, while the inhibition rates were
      50.0%, 69.9%, and 77.0% respectively when HT-29 cells were treated with 40 mg/L
      DHA for 24, 48, and 72 hours. The typical apoptotic morphologic changes of HT-29
      cells could be observed, including chromatin margination, nuclear condensation
      and apoptotic bodies. Gel electrophoresis of DNA degradation displayed typical
      DNA ladder fragments. HT-29 cells treated with DHA were arrested in G1 phase and
      the proportion of HT-29 cells in Gl phase increased compared with that of the
      control group (72.1% vs. 51.3%) while the proportion of the cells in S phase
      decreased significantly (19.9% vs. 38.9%). The content of n-6PUFA decreased, n
      3PUFA content increased and the ratio of n-6/n-3PUFA lowered significantly in
      colorectal cancer cells treated with DHA (P<0.01). CONCLUSIONS: n-3PUFA can
      inhibit the growth of human colorectal cancer cells via inhibition of the
      proliferation and induction of apoptosis. These effects may be associated with
      decrease in n-6/n-3PUFA ratio.

PMID- 22648846
TI  - [Influence of tumor size on the prognosis in patients with colon cancer].
AB  - OBJECTIVE: To investigate the impact of tumor size on the prognosis of patients
      with colon cancer. METHODS: The clinicopathologic factors of 345 cases who
      underwent curative surgery for colon cancer from January 2004 to June 2008 in the
      Peking University Cancer Hospital were analyzed retrospectively. The optimal cut
      off value was determined by receiver-operator characteristic (ROC) analysis.
      RESULTS: The overall 3-year survival rate was 85.1%. The optimal cut-off value
      was found to be 5.0 cm. The survival rate of patients with tumor size >=5 cm and
      tumor size <5 cm was 79.5% and 90.5% respectively, and the difference was
      statistically significant(P=0.005). Multivariate analysis showed that
      preoperative CEA level (P=0.004), tumor size(P=0.020), regional lymph node
      metastasis(P=0.000), and lymphovascular invasion(P=0.002) were independent
      prognostic factors. Tumor size was significantly associated with overall survival
      in univariate and multivariate analyses in stage III( disease (P=0.011), but not
      in stage II( disease(P=0.827) using 5 cm as a cut-off. CONCLUSIONS: Tumor size of
      5 cm is an independent prognostic parameter for patients with stage III( colon
      cancer but not for stage II(. Determination of the association between tumor size
      and survival should be base on TNM staging.

PMID- 22648847
TI  - [Total laparoscopic sigmoid and rectal surgery combined with transanal endoscopic
      microsurgery].
AB  - OBJECTIVE: To investigate the feasibility and short-term outcomes of total
      laparoscopic sigmoid and rectal surgery combined with transanal endoscopic
      microsurgery(TEM). METHODS: The clinical data of 26 patients with colorectal
      carcinoma treated by total laparoscopic surgery with TEM between May 2010 and May
      2011 in the Shanghai Ruijin Hospital were retrospectively analyzed. RESULTS: All
      the 26 operations were successfully accomplished laparoscopically. There was no
      conversion to open procedure. No diverting ileostomy was made. The mean operative
      time was (151.6+/-25.9) min. The mean blood loss was (200.2+/-114.7) ml. The mean
      time to first flatus was (2.0+/-0.5) d. The mean tumor size was (3.0+/-0.7) cm
      and all resection margins were negative. The mean number of lymph nodes harvested
      was (12.9+/-2.2). Six patients developed postoperative anastomotic leakage, all
      of who had tumors in the lower rectum. There were no ureteral injury, intestinal
      obstruction, or pulmonary infection. CONCLUSIONS: Total laparoscopic sigmoid and
      rectal surgery combined with TEM is a safe and feasible minimally invasive
      surgery. It is an improvement by combining laparoscopic skills with the concept
      of natural orifice transluminal endoscopic surgery.

PMID- 22648848
TI  - [Clinical analysis of combined organ resection for T4b gastric cancer].
AB  - OBJECTIVE: To evaluate the outcomes of combined organ resection for T4b gastric
      cancer, and determine the operative indication and prognostic factors. METHODS:
      Clinical data of 96 cases with T4bN0-3bM0 gastric cancer treated with combined
      organ resection in Tianjin Cancer Hospital from 2001 to 2005 were analyzed
      retrospectively. RESULTS: Twelve patients developed postoperative complications,
      including pancreatic fistula (n=4), abdominal infection(n=5), pulmonary
      infection(n=3), all of which were managed with conservative treatment. There were
      no perioperative deaths. All the patients had postoperative follow up with a
      median of 73 months. The 1-, 3-, 5-year overall survival rates were 70.5%, 42.1%,
      and 23.5%, respectively. Univariate analysis showed that Borrmann type,
      histologic type, lymph node staging, and pancreatic invasion were associated with
      the survival in patients with T4b gastric cancer(both P<0.05). Multivariable
      analysis showed that lymph node staging and histologic type were independent
      prognostic factors(all P<0.05). CONCLUSION: For well differentiated gastric
      cancer with lymph node staging of pN0 or pN1, combined organ resection may offer
      survival benefit.

PMID- 22648849
TI  - [Transanal specimen extraction in laparoscopic colorectal resection].
AB  - OBJECTIVE: To investigate the feasibility and efficacy of transanal specimen
      extraction in laparoscopic colorectal resection. METHODS: From January 2009 to
      December 2010, transanal specimen extraction technique was performed in 12
      patients undergoing laparoscopic colorectal resection. The clinical data were
      retrospectively analyzed. RESULTS: There were 8 males and 4 females. The age
      ranged from 41 to 67 (mean, 58) years old. The mean operative time was (240+/-45)
      min, mean blood loss was (70+/-40) ml. There was no anastomotic leakage or
      stenosis. One patient with constipation suffered from intractable right lower
      abdominal pain and was managed with antispasmodic agents. The frequency of bowel
      movements was 3-7/d in the 5 patients with constipation and 1-2/d in patients
      with colorectal carcinoma at six months postoperatively. No local recurrence and
      metastasis in patients with colorectal cancer after follow-up of 1-20 months.
      CONCLUSION: Transanal specimen extraction in laparoscopic colorectal resection is
      feasible, safe, and reliable.

PMID- 22648850
TI  - [Kiss-1 gene expression after radiation and its association with proliferation
      and apoptosis in colorectal cancer cells].
AB  - OBJECTIVE: To investigate the change of expression level of metastasis suppressor
      gene Kiss-1 in the colorectal cancer cell line SW480 after radiation, and to
      determine its association with the proliferation and apoptosis of SW480 cells.
      METHODS: SW480 cells were divided into control group (0 Gy) and study groups (2,
      4, 6, 8 Gy). Cells in the study groups were irradiated by 6-MV X-ray radiation
      for 48 hours. Immunohistochemistry and real-time PCR methods were used to
      investigate the influence of radiation on Kiss-1 gene expression of SW480. Colony
      formation assay was used to detect the proliferation of SW480. Flow cytometry
      Annexin- V/PI assay was used to observe the change of the apoptosis rate.
      RESULTS: Compared with the control group, Kiss-1 protein expression increased
      after radiation of 6, 8 Gy (P<0.05), but no significant changes were observed
      after radiation of 2, 4 Gy(P>0.05). Kiss-1 gene mRNA level increased after
      radiation of 2, 4, 6 Gy, while no obvious change was observed for 8 Gy radiation.
      The apoptosis rates increased for 4, 6, 8 Gy radiation(P<0.05), however, there
      was no significant difference for 2 Gy radiation (P<0.05). CONCLUSION: Radiation
      may increase Kiss-1 gene expression in SW480 cells, which results in decreases
      proliferation and increases apoptosis in residual surviving cells.

PMID- 22648851
TI  - [An experimental study on chemoprevention of esophageal adenocarcinoma by
      celecoxib, a selective cyclooxygenase-2 inhibitor].
AB  - OBJECTIVE: To study the feasibility of chemoprevention of esophageal
      adenocarcinoma by celecoxib, a selective cyclooxygenase-2(COX-2) inhibitor using
      a rat model. METHODS: Rats were divided into 3 groups: model group, celecoxib
      group, and control group. The rat surgical model was established by performing a
      gastrojejunostomy plus an esophagojejunostomy 5 mm distal to the gastrojejunal
      anastomosis. Twenty-eight weeks after surgery, all the animals were sacrificed
      and the pathological changes in the esophagus were examined macroscopically. COX
      2 expression was analyzed by immunohistochemistry. Prostaglandin E2(PGE2) level
      was measured by enzyme-linked immunosorbent assay(ELISA). RESULTS: The incidence
      of Barrett's esophagus and esophageal adenocarcinoma in the model group was 84%
      and 57% respectively, significantly higher than those in the control
      group(P<0.01). The incidence of esophageal adenocarcinoma in the celecoxib
      treated group was significantly lower than that in the model group(P<0.01), and
      no esophageal adenocarcinoma was detected in the control group. COX-2 expression
      was detected in 100% of reflux esophagitis, Barrett esophagus and esophageal
      adenocarcinoma, but not found in the normal tissue from the esophagus and the
      jejunum(P<0.01). The PGE2 level in the esophageal tissue in the model group was
      significantly higher than that in the control group(P<0.01). Rats in the
      celecoxib-treated group had significantly lower PGE2 level than that in the model
      group(P<0.01). The PGE2 levels were significantly higher in rats with cancer than
      those without cancer(P<0.01). CONCLUSION: Celecoxib successfully prevents the
      development of esophageal adenocarcinoma in a rat surgical model with mixed
      reflux of acid and duodenal juice and significantly decreases the risk of Barrett
      esophagus developing esophageal adenocarcinoma. COX-2 maybe an effective
      selective target of chemoprevention for esophageal adenocarcinoma.

PMID- 22648852
TI  - [Short-term outcomes of radical resection of rectal carcinoma: hand-assisted
      laparoscopy versus traditional laparoscopic approach].
AB  - OBJECTIVE: To study the feasibility of hand-assisted laparoscopic radical
      resection of rectal carcinoma and compare the short-term outcomes of HALS versus
      traditional laparoscopy approach. METHODS: Clinical data of 42 cases of rectal
      carcinoma between January 2010 and March 2011 were enrolled in this study.
      Nineteen cases underwent HALS total mesorectal excision and 23 cases underwent
      traditional laparoscopy approach. RESULTS: All the operations were successfully
      accomplished without conversions to open surgery. The mean operation time of the
      HALS group was shorter than that of the traditional laparoscopic group  (152 min
      vs. 168 min, P=0.009). Incision length was significantly longer in the HALS group
      (5.6 cm vs. 4.5 cm, P=0.000). The median overall costs were lower in HALS group
      (26 000 RMB vs. 29 000 RMB, P=0.008). The number of lymph nodes in resected
      specimen, intra-operative blood loss, length of hospital stay, time to passage of
      flatus were comparable between the two groups. CONCLUSIONS: Hand-assisted
      laparoscopic surgery has the advantages of laparoscopic surgery including minimal
      invasiveness, safety, and quicker postoperative recovery.

PMID- 22648853
TI  - [Intestinal dysfunction and enteral nutrition].
AB  - In recent years, it has been realized that intestinal function plays an
      increasingly important role in the treatment of critically ill patients.
      Awareness of intestinal dysfunction becomes more and more important. Enteral
      nutrition is an effective method for the recovery of intestinal function, and
      enteral nutrition is closely related to reliable administration route.
      Percutaneous endoscopic gastrostomy(PEG) is a minimally invasive, simple, safe
      and effective enteral nutrition route.

PMID- 22648854
TI  - Effects of three low-molecular-weight organic acids (LMWOAs) and pH on the
      mobilization of arsenic and heavy metals (Cu, Pb, and Zn) from mine tailings.
AB  - Natural organic acids may play an important role in influencing the mobility of
      toxic contaminants in the environment. The mobilization of arsenic (As) and heavy
      metals from an oxidized Pb-Zn mine tailings sample in the presence of three low
      molecular-weight organic acids, aspartic acid, cysteine, and succinic acid, was
      investigated at a mass ratio of 10 mg organic additive/g mine tailings in this
      study. The effect of pH was also evaluated. The mine tailings sample, containing
      elevated levels of As (2,180 mg/kg), copper (Cu, 1,100 mg/kg), lead (Pb, 12,860
      mg/kg), and zinc (Zn, 5,075 mg/kg), was collected from Bathurst, New Brunswick,
      Canada. It was found that the organic additives inhibited As and heavy metal
      mobilization under acidic conditions (at pH 3 or 5), but enhanced it under
      neutral to alkaline conditions (at pH above 7) through forming aqueous organic
      complexes. At pH 11, As, Cu, Pb, and Zn were mobilized mostly by the organic
      additives, 45, 46, 1,660, and 128 mg/kg by aspartic acid, 31, 28, 1,040, and 112
      mg/kg by succinic acid, and 53, 38, 2,020, and 150 mg/kg by cysteine,
      respectively, whereas those by distilled water were 6, 16, 260, and 52 mg/kg,
      respectively. It was also found that the mobilization of As and the heavy metals
      was closely correlated, and both were closely correlated to Fe mobilization.
      Arsenic mobilization by the three LMWOAs was found to be consistent with the
      order of the stability of Fe-, Cu-, Pb-, and Zn-organic ligand complexes. The
      organic acids might be used potentially in the natural attenuation and
      remediation of As and heavy metal-contaminated sites.

PMID- 22648856
TI  - Free-breathing multiphase whole-heart coronary MR angiography using image-based
      navigators and three-dimensional cones imaging.
AB  - Noninvasive visualization of the coronary arteries in vivo is one of the most
      important goals in cardiovascular imaging. Compared to other paradigms for
      coronary MR angiography, a free-breathing three-dimensional whole-heart iso
      resolution approach simplifies prescription effort, requires less patient
      cooperation, reduces overall exam time, and supports retrospective reformats at
      arbitrary planes. However, this approach requires a long continuous acquisition
      and must account for respiratory and cardiac motion throughout the scan. In this
      work, a new free-breathing coronary MR angiography technique that reduces scan
      time and improves robustness to motion is developed. Data acquisition is
      accomplished using a three-dimensional cones non-Cartesian trajectory, which can
      reduce the number of readouts 3-fold or more compared to conventional three
      dimensional Cartesian encoding and provides greater robustness to motion/flow
      effects. To further enhance robustness to motion, two-dimensional navigator
      images are acquired to directly track respiration-induced displacement of the
      heart and enable retrospective compensation of all acquired data (none discarded)
      for image reconstruction. In addition, multiple cardiac phases are imaged to
      support retrospective selection of the best phase(s) for visualizing each
      coronary segment. Experimental results demonstrate that whole-heart coronary
      angiograms can be obtained rapidly and robustly with this proposed technique.

PMID- 22648857
TI  - Hematopoietic progenitor constituents and adherent cell progenitor morphology
      isolated from black-rumped agouti (Dasyprocta prymnolopha, Wagler 1831) bone
      marrow.
AB  - Stem cells are present in the adult tissues of most diverse species. Bone marrow
      is recognized to be the most exploited site to obtain stem cells and cell
      progenitors. The objective of the present study was to characterize hematopoietic
      progenitor (HP) morphology and analyze the performance of adherent cell
      progenitors (ACPs) cultivated in vitro from black-rumped agouti bone marrow
      (Dasyprocta prymnolopha). Bone marrow aspirates were obtained from tibia crest
      and used to prepare histological slides and identify cell morphology. Cells were
      also scattered on culture plates for later isolation, expansion, and
      quantification. Smears obtained from bone marrow demonstrated HPs at different
      stages of maturity. In culture, these cells showed fibroblastoid morphology and a
      strong tendency to form colonies, demonstrated by the presence of cell
      aggregates, cytoplasmic elongations lying side by side. An 80% cell confluence
      was observed at 18 days in culture and progressive reduction in the percentage of
      nonadherent mononuclear cells. After eight passes, a mean cell viability of
      96.07% was observed, from a pool of 1.6 * 10(7) cells (ACP). Thirteen 25-cm(2)
      culture bottles were trypsinized, resuspended in freezing medium, stored in 14
      criotubes at a concentration of 1 * 10(6) cells per milliliter, and placed in
      liquid nitrogen at -196 degrees C. Agouti bone marrow demonstrated high
      plasticity, moreover different HP lines, and a population of adherent cells
      demonstrated morphology similar to mesenchymal stem cells in culture.

PMID- 22648855
TI  - The sox gene Dichaete is expressed in local interneurons and functions in
      development of the Drosophila adult olfactory circuit.
AB  - In insects, the primary sites of integration for olfactory sensory input are the
      glomeruli in the antennal lobes. Here, axons of olfactory receptor neurons
      synapse with dendrites of the projection neurons that relay olfactory input to
      higher brain centers, such as the mushroom bodies and lateral horn. Interactions
      between olfactory receptor neurons and projection neurons are modulated by
      excitatory and inhibitory input from a group of local interneurons. While
      significant insight has been gleaned into the differentiation of olfactory
      receptor and projection neurons, much less is known about the development and
      function of the local interneurons. We have found that Dichaete, a conserved Sox
      HMG box gene, is strongly expressed in a cluster of LAAL cells located adjacent
      to each antennal lobe in the adult brain. Within these clusters, Dichaete protein
      expression is detected in both cholinergic and GABAergic local interneurons. In
      contrast, Dichaete expression is not detected in mature or developing projection
      neurons, or developing olfactory receptor neurons. Analysis of novel viable
      Dichaete mutant alleles revealed misrouting of specific projection neuron
      dendrites and axons, and alterations in glomeruli organization. These results
      suggest noncell autonomous functions of Dichaete in projection neuron
      differentiation as well as a potential role for Dichaete-expressing local
      interneurons in development of the adult olfactory circuitry.

PMID- 22648858
TI  - Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults.
AB  - BACKGROUND: The cause of chronic fatigue syndrome (CFS) is unknown but is thought
      to be associated with immune abnormalities or infection. Because cancer can arise
      from similar conditions, associations between CFS and cancer were examined in a
      population-based case-control study among the US elderly. METHODS: Using linked
      Surveillance, Epidemiology, and End Results (SEER)-Medicare registry data,
      approximately 1.2 million cancer cases and 100,000 controls (age range, 66-99
      years; 1992-2005) were evaluated. CFS was identified in the period more than 1
      year prior to selection, using linked Medicare claims. Unconditional logistic
      regression was used to estimate the odds ratios (ORs) comparing the CFS
      prevalence in cases and controls, adjusting for age, sex, and selection year. All
      statistical tests were 2-sided. RESULTS: CFS was present in 0.5% of cancer cases
      overall and 0.5% of controls. CFS was associated with an increased risk of non
      Hodgkin lymphoma (NHL) (OR = 1.29, 95% confidence interval [CI] = 1.16-1.43, P =
      1.7 * 10(-6) ). Among NHL subtypes, CFS was associated with diffuse large B cell
      lymphoma (OR = 1.34, 95% CI = 1.12-1.61), marginal zone lymphoma (OR = 1.88, 95%
      CI = 1.38-2.57), and B cell NHL not otherwise specified (OR = 1.51, 95% CI = 1.03
      2.23). CFS associations with NHL overall and NHL subtypes remained elevated after
      excluding patients with medical conditions related to CFS or NHL, such as
      autoimmune conditions. CFS was also associated, although not after multiple
      comparison adjustment, with cancers of the pancreas (OR = 1.25, 95% CI = 1.07
      1.47), kidney (OR = 1.27, 95% CI = 1.07-1.49), breast (OR = 0.85, 95% CI = 0.74
      0.98), and oral cavity and pharynx (OR = 0.70, 95% CI = 0.49-1.00). CONCLUSIONS:
      Chronic immune activation or an infection associated with CFS may play a role in
      explaining the increased risk of NHL.

PMID- 22648860
TI  - Direct measurement of phage phi29 stiffness provides evidence of internal
      pressure.
AB  - Using AFM nanoindentation experiments, DNA-full phi29 phage capsids are shown to
      be stiffer than when empty. The presence of counterions softens full viruses in a
      reversible manner, indicating that pressure originates from the confined DNA. A
      finite element analysis of the experiments provides an estimate of the pressure
      of ~40 atm inside the capsid, which is similar to theoretical predictions.

PMID- 22648861
TI  - Ultrasound criteria and CA 125 as predictive variables of ovarian cancer in women
      with adnexal tumors.
AB  - OBJECTIVES: To evaluate the capacity to predict malignancy in women with adnexal
      tumors using CA 125 measurement and ultrasound criteria. METHODS: This was a
      cross-sectional study including 103 women with a total of 110 adnexal tumors. CA
      125 level was measured in a sample of peripheral blood. Lesions were classified
      by ultrasound, using standardized predetermined criteria, as benign (B) or
      malignant (M). Those that could not be classified by these criteria were assessed
      subjectively. Histopathologic examination of surgical specimens was used as the
      gold standard. RESULTS: Of 110 tumors, 79 (71.8%) were benign and 31 (28.2%) were
      malignant on histopathology. Ultrasound criteria could be applied to 91 (82.7%)
      tumors, resulting in a sensitivity of 90%, specificity of 87%, positive
      predictive value (PPV) of 69% and negative predictive value (NPV) of 97%. In
      tumors not classifiable according to ultrasound criteria, subjective sonographic
      assessment gave a sensitivity of 67%, specificity of 80%, PPV of 75% and NPV of
      73%. At a cut-off point of 37.4 U/mL, CA 125 had a sensitivity of 69%, a
      specificity of 87.8%, a PPV of 69% and a NPV of 88% for detection of malignancy.
      When CA 125 was associated with age and ultrasound criteria in a logistic
      regression model, the sensitivity and specificity increased in the subset of
      sonographically malignant tumors. CONCLUSION: The majority of tumors were
      correctly classified using ultrasound criteria. CA 125 alone performed worse than
      did ultrasound in discriminating malignant from benign adnexal tumors. CA 125
      measurement contributed to the diagnosis of malignancy, improving overall
      specificity, only in sonographically malignant tumors.

PMID- 22648862
TI  - Oral supplementation of butyrate reduces mucositis and intestinal permeability
      associated with 5-Fluorouracil administration.
AB  - Mucositis affects about 40 % of patients undergoing chemotherapy. Short chain
      fatty acids (SCFA), mainly butyrate, are claimed to improve mucosal integrity,
      reduce intestinal permeability and act as anti-inflammatory agents for the colon
      mucosa. We evaluated the effects of oral administration of SCFA or butyrate in
      the 5FU-induced mucositis. Mice received water, SCFA or butyrate during all
      experiment (10 days) and a single dose of 5FU (200 mg/kg) 3 days before
      euthanasia. We evaluated inflammatory and histological score by morphometry, and
      by activity of enzymes specific to neutrophil, eosinophil and macrophage and TLR
      4, TNF-alpha and IL6 expressions. Intestinal permeability and tight junction
      protein ZO-1 expression were evaluated. Mice from the 5FU  (5-Fluorouracil) group
      presented weight loss, ulcerations and inflammatory infiltration of neutrophils
      and eosinophils, increased expression of IL6 and TNF-alpha and increased
      intestinal permeability. SCFA minimized intestinal damage, reduced ulcerations
      without affecting intestinal permeability. Butyrate alone was more efficient at
      improving those parameters than in SCFA solution and also reduced intestinal
      permeability. The expression of pro-inflammatory cytokines and ZO-1 tended to be
      higher in the SCFA supplemented but not in the butyrate supplemented group. We
      showed the beneficial effects of butyrate on intestinal mucositis and its
      promising function as an adjuvant in the treatment of diseases not only of the
      colon, but also of the small intestine.

PMID- 22648863
TI  - Native-state solubility and transfer free energy as predictive tools for
      selecting excipients to include in protein formulation development studies.
AB  - In the present report, two formulation strategies, based on different aggregation
      models, were compared for their ability to quickly predict which excipients
      (cosolutes) would minimize the aggregation rate of an immunoglobulin G1
      monoclonal antibody (mAb-1) stored for long term at refrigerated and room
      temperatures. The first formulation strategy assumed that a conformational change
      to an aggregation-prone intermediate state was necessary to initiate the
      association process and the second formulation strategy assumed that protein self
      association was instead controlled by the solubility of the native state. The
      results of these studies indicate that the stabilizing effect of excipients
      formulated at isotonic concentrations is derived from their ability to solubilize
      the native state, not by the increase of protein conformational stability induced
      by their presence. The degree the excipients solvate the native state was
      determined from the apparent transfer free energy of the native state from water
      into each of the excipients. These values for mAb-1 and two additional
      therapeutic antibodies correlated well to their long-term 4 degrees C and room
      temperature aggregation data and were calculated using only the literature values
      for the apparent transfer free energies of the amino acids into the various
      excipients and the three-dimensional models of the antibodies.

PMID- 22648864
TI  - Extremely thin bilayer electrolyte for solid oxide fuel cells (SOFCs) fabricated
      by chemical solution deposition (CSD).
AB  - An extremely thin bilayer electrolyte consisting of yttria-stabilized zirconia
      (YSZ) and gadolinia-doped ceria (GDC) is successfully fabricated on a sintered
      NiO-YSZ substrate. Major processing flaws are effectively eliminated by applying
      local constraints to YSZ nanoparticles, and excellent open circuit voltage and
      cell performance are demonstrated in a solid oxide fuel cell (SOFC) at
      intermediate operating temperatures.

PMID- 22648865
TI  - Next generation sequencing: chemistry, technology and applications.
AB  - High-throughput next generation sequencing (NGS) has been quickly adapted into
      many aspects of biomedical research and begun to engage with the clinical
      practice. The latter aspect will enable the application of genomic knowledge into
      clinical practice in this and next decades and will profoundly change the
      diagnosis, prognosis and treatment of many human diseases. It will further demand
      both philosophical and medical curriculum reforms in the training of our future
      physicians. However, significant huddles need to be overcome before an ultimate
      application of NGS in genomic medicine can be practical and fruitful. 

PMID- 22648866
TI  - Trypanosomal Trans-sialidases: Valuable Synthetic Tools and Targets for Medicinal
      Chemistry.
AB  - In contrast to the general hydrolases, trans-sialidase from Trypanosoma cruzi
      (TcTS) shows excellent regio- and stereoselectivity as well as high yields in
      transfer reactions. Discussed are the occurrence of trans-sialidases and studies
      on the transfer mechanism. In detail, the preparative use by chemoenzymatic
      syntheses with TcTS are outlined with emphasis on the design of modified donor
      and acceptor substrates. Another section focuses on attempts to develop
      inhibitors for TcTS, and these endeavors are based on donor- and acceptor
      inspired modifications as well as on some completely different structures. 

PMID- 22648867
TI  - Reoptimized interaction parameters for the peptide-backbone model compound N
      methylacetamide in the GROMOS force field: influence on the folding properties of
      two beta-peptides in methanol.
AB  - Considering N-methylacetamide (NMA) as a model compound, new interaction
      parameters are developed for the amide function in the GROMOS force field that
      are compatible with the recently derived 53A6(OXY) parameter set for oxygen
      containing chemical functions. The resulting set, referred to as 53A6(OXY+A) ,
      represents an improvement over earlier GROMOS force-field versions in the context
      of the pure-liquid properties of NMA, including the density, heat of
      vaporization, dielectric permittivity, self-diffusion constant and viscosity, as
      well as in terms of the Gibbs hydration free energy of this molecule. Assuming
      that NMA represents an adequate model compound for the backbone of peptides,
      53A6(OXY+A) may be expected to also provide an improved description of
      polypeptide chains. As an initial test, simulations are reported for two beta
      peptides characterized by very different folding properties in methanol. For
      these systems, earlier force-field versions provided good agreement with
      experimental NMR data, and the test shows that the improved description achieved
      in the context of NMA is not accompanied by any deterioration in the
      representation of the conformational properties of these peptides.

PMID- 22648869
TI  - Psychosocial factors affecting various types of intimate partner violence against
      women.
AB  - OBJECTIVE: Intimate partner violence against women is a growing global public
      health problem that is related to various psychosocial, cultural, mental, and
      economic factors. In this study, psychosocial factors affecting various types of
      intimate partner violence against women were investigated based upon affected
      individuals' statements. METHODS: Demographic data, exposure to various types of
      partner violence, individual habits, partner habits, family functioning, and
      social support were inquired about during face to face interviews with 306 women
      chosen by stratified sampling to represent adult women living in Edirne, Turkey.
      RESULTS: Among the participants, 54.5% were exposed to psychological violence,
      30.4% were exposed to physical violence, 19.3% were exposed to economic violence,
      and 6.3% were exposed to sexual violence. Partner's age and the duration of
      marriage had a protective effect on intimate partner violence while worsening of
      marital relations, marriage by family decision, marriage against family consent,
      and the presence of a violent history against women in a partner's family had
      incremental effects on intimate partner violence. The duration of marriage, the
      worsening of marital relations and a history of violent exposure during childhood
      increased physical violence. Additionally, a decreasing family income, increasing
      economic violence, worsening of marital relations, and a decreasing social
      support network increased sexual violence against women. CONCLUSIONS: Recognizing
      and defining the effecting factors of intimate partner violence will aid in the
      understanding of the sources that generate and feed the violent behavior. Risk
      factors of different types of intimate partner violence vary. Our results
      indicate that any kind of violent behavior increases intimate partner violence
      against women.

PMID- 22648870
TI  - Prevelance of mental disorders and associated factors in institutionalized 3-5
      year old children.
AB  - OBJECTIVE: In this study, we aimed to determine the prevelance and severity of
      mental disorders in institutionalized children between the ages of 3-5 years,
      investigate the factors associated with the mental disorders and compare these
      findings with the data of a community sample composed of children who were raised
      by their own families. METHOD: Thirty-four children raised in three institutions
      in Kocaeli were compared with an age- and sex-matched community sample. Children
      were assessed according to DSM-IV diagnostic criteria. The Socio-demographic
      information form, and Early Childhood Inventory-4 (ECI-4) parent scale were used
      for data collection. RESULTS: Children that were reared in institutions had
      evidence of higher rates of mental disorders. In institution-reared children,
      symptom severity of attention deficit hyperactivity disorder, reactive attachment
      disorder, oppositional deficient disorder, and pervasive developmental disorder
      were higher than the community subjects. Age, time spent with father, duration of
      institutionalization, number of siblings, number of hospital admissions because
      of physical symptoms and presence of abuse before institutional care were
      determined to be predictive factors for psychiatric symptoms. CONCLUSION: These
      findings revealed that institutionalized children are at risk for mental
      disorders and protective measures are as important as instutional care for these
      children. Our results suggest that essential steps should be taken to protect the
      mental health of children in institutional care.

PMID- 22648868
TI  - Variable response to propranolol treatment of kaposiform hemangioendothelioma,
      tufted angioma, and Kasabach-Merritt phenomenon.
AB  - Propranolol is a non-selective beta-adrenergic antagonist successfully used in a
      case of kaposiform hemangioendothelioma (KHE) associated with Kasabach-Merritt
      phenomenon (KMP). We report 11 patients treated with propranolol for KHE and the
      related variant tufted angioma (TA), six of whom also had KMP. The varied
      responses to treatment, with only 36% responding in our series, demonstrate the
      need for further study of this medication before routine use for these
      indications.

PMID- 22648871
TI  - The prevalence of death ideation and attempted suicide and the associated risk
      factors in Isparta, Turkey.
AB  - OBJECTIVE: Suicide is a complex process from the initiation of ideation to
      planning, and finally to an attempt. This study aimed to investigate the
      prevalence of death ideation, attempted suicide, and the associated risk factors
      in Isparta, Turkey. MATERIALS AND METHODS: The study included 600 participants
      aged 18-65 years representative of the population of central Isparta that were
      selected via the stratified simple randomized sampling method. The participants
      were administered a questionnaire for collecting demographic data, and the
      participant's experiences of death ideations and suicide attempts, and the
      clinical version of SCID were used. RESULTS: The lifetime prevalence of attempted
      suicide and death ideations was 4.3% and 27.5%, respectively. Death ideas and
      attempted suicide were both more prevalent among women and younger adults. All
      those that attempted suicide were exposed to a stress factor prior to the
      attempt. The rates of death ideation and attempted suicide were lower among the
      participants that had children. A family history of attempted suicide was
      associated with an increase in the frequency of death ideations and attempted
      suicide. Attempted suicide and death ideas were more common among those with
      major depressive disorder. Generalized anxiety disorder was observed
      significantly more frequently among those that had attempted suicide. Panic
      disorder and a specific phobia were also significantly associated with death
      ideation. CONCLUSION: The present study's findings indicate that there were
      common risk factors for attempted suicide and death ideations in the study group.
      Determination of the prevalence of attempted suicide and death ideation in a
      population, identification of the associated risk factors and assessment of their
      relationship to mental disorders can facilitate a better understanding of
      suicidal behaviour.

PMID- 22648872
TI  - The effects of age at circumcision on premature ejaculation.
AB  - OBJECTIVE: The objective of this study was to analyze the effect of age at
      circumcision on premature ejaculation (PE). MATERIALS AND METHODS: The study
      included 40 healthy male controls and 40 male patients diagnosed as PE according
      to American Psychiatric Association criteria and the Golombok-Rust Inventory of
      Sexual Satisfaction (GRISS) premature ejaculation subscale. The 2 groups were
      compared according to age at circumcision and GRISS score. RESULTS: The PE group
      and control group were sociodemographically similar, but differed in marital
      status. The groups differed in GRISS communication, degree of satisfaction,
      avoidance, sensuality, erectile dysfunction, and PE subscale scores. These
      differences only displayed a dysfunction in the degree of satisfaction and
      premature ejaculation subscales. The groups also differed in age at circumcision;
      accordingly, those that were circumcised at >=7 years of age had higher GRISS
      scores and a higher risk of having PE than those that were circumcised at >7
      years of age. CONCLUSION: Age at circumcision had an effect on PE; circumcision
      at >=7 years of age was associated with an increase in the risk of PE, as
      compared to circumcision at >7 years of age. We think that families should have
      their boys circumcised before the age of 7 years and highly recommend that the
      procedure be performed within in the first 3 years of life.

PMID- 22648873
TI  - The validity and reliability of Turkish version of separation anxiety symptom
      inventory and adult separation anxiety questionnaire.
AB  - AIM: The aim of this study is to evaluate the validity and reliability of
      Separation Anxiety Symptoms Inventory (SASI) that assess childhood separation
      anxiety retrospectively and Adult Separation Anxiety Questionnaire (ASA). METHOD:
      The study sample included a group of 410 participants comprised of 282 adult
      psychiatric outpatients with anxiety and/or major depressive disorders according
      to DSM-IV criteria and 128 nonpsychiatric control subjects. The presence of
      psychiatric disorders was determined by using the M.I.N.I. (Mini International
      Neuropsychiatric Interview). Structured Clinical Interview for Separation Anxiety
      Symptoms (SCI-SAS), Separation Anxiety Symptoms Inventory (SASI), Adult
      Separation Anxiety Questionnaire (ASA), Panic Disorder Severity Scale (PDSS),
      "Sensitivity to Separations" subscale of Panic Agorapfobic Spectrum Scale (PAS
      SR), Anxiety Sensitivity Index (ASI) were also given. FINDINGS: The validity
      assessments of the instruments revealed that SASI and ASA discriminated the
      psychiatric patients from control subjects. Both instruments displayed high
      correlation with SCI-SAS and PAS-SR, a moderate correlation with ASI and PDSS.
      Factor structure assessments revealed the existence of 3 factor for SASI and 5
      factor for ASA. Both SASI and ASA has a high level of internal consistency
      (Cronbach alfa coefficients are 0.89 and 0.93 respectively) and their test-retest
      reliability is fairly good. RESULTS: Turkish versions of SASI and ASA were found
      to be valid and reliable. Results indicate that those instruments can be used in
      clinical studies for surveying adult separation anxiety disorder and determining
      its severity.

PMID- 22648874
TI  - Is the neo-Kraepelinian paradigm in a phase of crisis?.
AB  - The neo-Kraepelinian paradigm has been the dominant paradigm in psychiatry since
      the introduction of DSM-III in 1980. Though successful in achieving reliability
      and in some other respects, it also has limitations. Lately, it has been argued
      that a paradigm shift is needed in psychiatric diagnosis. The aim of this paper
      is to review evidence of the limitations of DSM and to determine whether our
      classification system is in a phase of crisis in the Kuhnian sense.   The most
      important criticisms raised since the early eighties include: the psychodynamic
      objection, the descriptive approach criticism, the criticism of poor diagnostic
      validity, and Ozturk's critique. The author concludes that these old objections
      are not a real threat. In particular, problems stemming from the descriptive
      approach and low diagnostic validity are not attributable to DSM but are due to
      under-achievements in psychiatry.   On the other hand, the new problems seem more
      serious and may be considered signs of crisis. These include high rates of false
      positives, high levels of pseudo-comorbidity, and other deficiencies attributed
      to the categorical approach. However, because of the advantages of this approach
      and the lack of a serious candidate available to replace it, a paradigm shift
      seems highly unlikely. The real source of the problem is not the categorical
      model but the low validity of some of our categories. If our etiopathological
      understanding of all the categories were to reach that of medical disorders, no
      paradigm shift would seem necessary.

PMID- 22648875
TI  - Psychiatric disorders and epigenetics.
AB  - The term epigenetic refers to long-lasting changes in gene expression that are
      beyond the DNA base sequence. Understanding the dynamic role of epigenetic
      mechanisms in the regulation of gene expression in adulthood has led researchers
      to investigate epigenetic mechanisms in psychiatric disorders. The aim of this
      review was to describe epigenetic mechanisms and to discuss the role of
      epigenetic modifications in stress, depression, schizophrenia, and substance
      dependence. For this purpose PubMed was searched using the keywords epigenetic,
      stress, depression, schizophrenia, and substance dependence; studies published
      between 2000 and 2011 were reviewed.    Different maternal behavioral patterns
      and early life stress have been reported to yield heritable changes in gene
      expression via epigenetic mechanisms, which are reversible. Studies that
      investigated the role of epigenetic modifications in stress and depression
      focused on the proteins involved in the regulation of the hypothalamo-pituitary
      adrenal (HPA) axis, whereas epigenetic studies of schizophrenia primarily focused
      on changes in the GABAergic system. Studies on substance dependence, on the other
      hand, showed that substance use might change the expression of many genes by
      causing short- or long-lasting epigenetic modifications.  These findings have led
      to the development of new therapeutic strategies that target epigenetic
      mechanisms. Among these strategies, histone deacetylase inhibitors are especially
      promising. More studies are needed to improve our understanding of the role of
      epigenetic modifications in the development of psychiatric disorders, and to aid
      in the development of new treatment strategies that focus on epigenetic
      mechanisms.

PMID- 22648876
TI  - Jactatio corporis nocturna and dissociative disorder: a case report.
AB  - Jactatio corporis nocturna is a type of parasomnia. Rhythmic body movements
      during sleep are commonly observed in infancy and early childhood, and
      spontaneous resolution is expected after the age of 4 years. Rarely, the body
      movements persist until adulthood. Rhythmic body movements characteristically
      occur during the wake-sleep transition period, rather than during other sleep
      stages. Some psychiatric diseases can co-occur with sleep-related movement
      disorders. A relationship between parasomnias and dissociative disorders has been
      recently reported.    Herein we present a 33-year-old male with nocturnal
      repetitive rolling body movements and daytime fatigue. The patient also had loss
      of memory of some important events (such as the day his daughter underwent
      surgery), and reported that he sometimes confused reality with dreams had
      fantasies during which he experienced his spirit rising above to watch his body
      and fantasy. Detailed neuropsychological assessment showed that the patient also
      had a dissociative disorder. Video-polysomnographic recordings showed repetitive,
      rolling body movements that occurred only during rapid eye movement (REM) sleep.

PMID- 22648877
TI  - [Editorial].

PMID- 22648878
TI  - Is rhizosphere remediation sufficient for sustainable revegetation of mine
      tailings?
AB  - BACKGROUND: Revegetation of mine tailings (fine-grained waste material) starts
      with the reconstruction of root zones, consisting of a rhizosphere horizon
      (mostly topsoil and/or amended tailings) and the support horizon beneath (i.e.
      equivalent to subsoil - mostly tailings), which must be physically and hydro
      geochemically stable. This review aims to discuss key processes involved in the
      development of functional root zones within the context of direct revegetation of
      tailings and introduces a conceptual process of rehabilitating structure and
      function in the root zones based on a state transition model. SCOPE: Field
      studies on the revegetation of tailings (from processing base metal ore and
      bauxite residues) are reviewed. Particular focus is given to tailings' properties
      that limit remediation effectiveness. Aspects of root zone reconstruction and
      vegetation responses are also discussed. CONCLUSIONS: When reconstructing a root
      zone system, it is critical to restore physical structure and hydraulic functions
      across the whole root zone system. Only effective and holistically restored
      systems can control hydro-geochemical mobility of acutely and chronically toxic
      factors from the underlying horizon and maintain hydro-geochemical stability in
      the rhizosphere. Thereafter, soil biological capacity and ecological linkages
      (i.e. carbon and nutrient cycling) may be rehabilitated to integrate the root
      zones with revegetated plant communities into sustainable plant ecosystems. A
      conceptual framework of system transitions between the critical states of root
      zone development has been proposed. This will illustrate the rehabilitation
      process in root zone reconstruction and development for direct revegetation with
      sustainable plant communities. Sustainable phytostabilization of tailings
      requires the systematic consideration of hydro-geochemical interactions between
      the rhizosphere and the underlying supporting horizon. It further requires
      effective remediation strategies to develop hydro-geochemically stable and
      biologically functional root zones, which can facilitate the recovery of the
      microbial community and ecological linkages with revegetated plant communities.

PMID- 22648879
TI  - Cyanolichens can have both cyanobacteria and green algae in a common layer as
      major contributors to photosynthesis.
AB  - BACKGROUND AND AIMS: Cyanolichens are usually stated to be bipartite (mycobiont
      plus cyanobacterial photobiont). Analyses revealed green algal carbohydrates in
      supposedly cyanobacterial lichens (in the genera Pseudocyphellaria, Sticta and
      Peltigera). Investigations were carried out to determine if both cyanobacteria
      and green algae were present in these lichens and, if so, what were their roles.
      METHODS: The types of photobiont present were determined by light and
      fluorescence microscopy. Small carbohydrates were analysed to detect the presence
      of green algal metabolites. Thalli were treated with selected strengths of Zn(2+)
      solutions that stop cyanobacterial but not green algal photosynthesis. CO(2)
      exchange was measured before and after treatment to determine the contribution of
      each photobiont to total thallus photosynthesis. Heterocyst frequencies were
      determined to clarify whether the cyanobacteria were modified for increased
      nitrogen fixation (high heterocyst frequencies) or were normal, vegetative cells.
      KEY RESULTS: Several cyanobacterial lichens had green algae present in the
      photosynthetic layer of the thallus. The presence of the green algal transfer
      carbohydrate (ribitol) and the incomplete inhibition of thallus photosynthesis
      upon treatment with Zn(2+) solutions showed that both photobionts contributed to
      the photosynthesis of the lichen thallus. Low heterocyst frequencies showed that,
      despite the presence of adjacent green algae, the cyanobacteria were not altered
      to increase nitrogen fixation. CONCLUSIONS: These cyanobacterial lichens are a
      tripartite lichen symbiont combination in which the mycobiont has two primarily
      photosynthetic photobionts, 'co-primary photobionts', a cyanobacterium (dominant)
      and a green alga. This demonstrates high flexibility in photobiont choice by the
      mycobiont in the Peltigerales. Overall thallus appearance does not change whether
      one or two photobionts are present in the cyanobacterial thallus. This suggests
      that, if there is a photobiont effect on thallus structure, it is not specific to
      one or the other photobiont.

PMID- 22648880
TI  - Medieval emergence of sweet melons, Cucumis melo (Cucurbitaceae).
AB  - BACKGROUND: Sweet melons, Cucumis melo, are a widely grown and highly prized
      crop. While melons were familiar in antiquity, they were grown mostly for use of
      the young fruits, which are similar in appearance and taste to cucumbers, C.
      sativus. The time and place of emergence of sweet melons is obscure, but they are
      generally thought to have reached Europe from the east near the end of the 15th
      century. The objective of the present work was to determine where and when truly
      sweet melons were first developed. METHODS: Given their large size and sweetness,
      melons are often confounded with watermelons, Citrullus lanatus, so a list was
      prepared of the characteristics distinguishing between them. An extensive search
      of literature from the Roman and medieval periods was conducted and the findings
      were considered in their context against this list and particularly in regard to
      the use of the word 'melon' and of adjectives for sweetness and colour. FINDINGS:
      Medieval lexicographies and an illustrated Arabic translation of Dioscorides'
      herbal suggest that sweet melons were present in Central Asia in the mid-9th
      century. A travelogue description indicates the presence of sweet melons in
      Khorasan and Persia by the mid-10th century. Agricultural literature from
      Andalusia documents the growing of sweet melons, evidently casabas (Inodorous
      Group), there by the second half of the 11th century, which probably arrived from
      Central Asia as a consequence of Islamic conquest, trade and agricultural
      development. Climate and geopolitical boundaries were the likely causes of the
      delay in the spread of sweet melons into the rest of Europe.

PMID- 22648881
TI  - Patient views on examinations as part of asymptomatic screening in sexual health
      clinics.
AB  - Examinations of asymptomatic patients (AP) do not always take place in sexual
      health clinics, partly due to the evidence that clinically significant findings
      (not identified by urine and blood tests) are rarely found on examination of
      these patients. However, it is unclear from the literature as to whether
      patients, given the option, would choose to be examined when fully aware of what
      may be identified on examination as well as the frequency of positive findings. A
      total of 110 men attending a sexual health clinic who self-identified as
      asymptomatic were given a patient information sheet (PIS) describing the place
      and value (if any) of examinations in AP and were asked if they would like an
      examination. Of the 83 truly asymptomatic men with low sexual risk involved, 86%
      expressed the intention of having an examination having read the PIS.

PMID- 22648882
TI  - The contribution of antenatal care to the coverage and correlates of HIV testing
      among adults in Zimbabwe 2005-06.
AB  - Expanding the availability, utilization and coverage of HIV testing services is a
      critical step towards primary prevention and successful delivery of
      antiretroviral therapy (ART) in Zimbabwe. We used data from the Zimbabwe
      Demographic and Health Survey (2005-2006) to examine the coverage and correlates
      of recent HIV testing (HIV testing <24 months preceding the survey) among HIV
      positive and HIV-negative adults. We estimated the relative contribution of HIV
      testing in both the antenatal care (ANC) setting and non-ANC settings. Uptake of
      recent HIV testing was 14.4% among women and 11.1% among men, with HIV testing in
      ANC accounting for 42.3% and 10.3% of all recent testing among women and men,
      respectively. In the multivariate analyses, recent pregnancies and being aware of
      ART were independent correlates after controlling for demographic and
      socioeconomic variables. HIV testing in ANC was an important contributor to HIV
      testing coverage in Zimbabwe by reaching not only pregnant women but also their
      partners.

PMID- 22648883
TI  - HIV-1 drug resistance at virological failure versus immunological failure among
      patients failing first-line antiretroviral therapy in a resource-limited setting.
AB  - Antiretroviral treatment failure has been defined by immunological failure (IF)
      in some resource-limited settings whereas defining by virological failure (VF)
      has been widely used in developed countries. There is limited comparison of the
      levels of HIV-1 drug resistance between using VF and IF for the diagnosis of
      treatment failure. A retrospective cohort study was conducted among HIV-1
      infected patients failing first-line antiretroviral therapy (ART). Of 95
      patients, median CD4 and HIV-1 RNA were 158 cells/mm(3) and 10,200 copies/mL,
      respectively. Patients in the IF group had higher HIV-1 RNA than those in VF
      group (23,820 versus 9510 copies/mL, P = 0.008). Nucleoside reverse transcriptase
      inhibitor (NRTI)-, non-NRTI- and protease inhibitor-resistance-associated
      mutations (RAMs) were observed in 57.9%, 94.7% and 5.3%, respectively. Q151M, a
      multidrug RAM, was more commonly observed in the IF group (14.8% versus 2.9%, P =
      0.032). Using IF to diagnose treatment failure is associated with higher HIV-1
      RNA levels and a higher rate of Q151M, which can limit the options for second
      line ART.

PMID- 22648884
TI  - Simultaneous triple point-of-care testing for HIV, syphilis and hepatitis B virus
      to prevent mother-to-child transmission in India.
AB  - An innovative simultaneous triple point-of-care (STPOC) screening strategy for
      syphilis, hepatitis B and HIV with Determine((r)) tests was offered to pregnant
      women presenting for antenatal care and evaluated for feasibility and preference
      in rural India. Of 1066 participants approached, 1046 consented, of which 1002
      (96.0%) completed the strategy. Only 9% reported any history of testing in their
      current pregnancy. With STPOC screening, 989 women (98.7%) tested negative and 13
      had preliminary positive results for infection. The total time taken was 45
      minutes per participant. Mothers and infants were provided prophylaxis/treatment
      for HIV, syphilis and hepatitis B, with interventions initiated within 3-5 days.
      STPOC was preferred by 99.3% (95%CI: 98.8-99.8%) of participants, facilitated
      early simultaneous screening for the three infections, timely initiation of
      prophylaxis/treatment and was feasible in this rural setting. These data suggest
      that multiplexed STPOC screening for syphilis, hepatitis B and HIV in pregnancy
      would be desirable for women in rural India.

PMID- 22648885
TI  - Prevalence of sexually transmitted infections among women attending antenatal
      clinics in Tanga, north eastern Tanzania.
AB  - This study aimed to determine the prevalence of sexually transmitted infections
      (STIs) among HIV-infected and uninfected pregnant women in Tanga, Tanzania.
      Retrospective data on syphilis and HIV status during 2008-2010 were collected
      from antenatal clinic (ANC) records. Prospective data were collected from HIV
      infected (n = 105) and HIV-uninfected pregnant women (n = 100) attending ANCs
      between April 2009 and August 2010. Syphilis prevalence showed a declining trend
      (3.1%, 1.4% and 1.3%), while HIV prevalence was stable (6.1%, 6.4% and 5.4%)
      during 2008-2010. HIV-infected women had significantly higher prevalence of
      trichomoniasis (18.8% versus 5.0%; P < 0.003) and candidiasis (16.5% versus 2.0%;
      P < 0.001) while the higher rate of gonorrhoea (3.5% versus 0%; P = 0.095) was
      not statistically significant when compared with HIV-uninfected women. There were
      no statistically significant differences in prevalence of chlamydial infection
      (0% versus 3.0%; P = 0.156) or syphilis (2.4% versus 3.0%; P = 1) between HIV
      infected and uninfected women. Other STIs were common in both HIV-infected and
      uninfected pregnant women.

PMID- 22648886
TI  - A surgical approach to anogenital disease: guidance on providing a minor surgery
      service in sexual health and genitourinary medicine.
AB  - Certain anogenital conditions require surgical intervention and although the
      specialty training curriculum for genitourinary (GU) medicine mentions skin
      biopsy as the only surgical skill required for training, most practitioners could
      usefully provide a more extensive surgical or 'minor ops' service. The purpose of
      this paper is to provide guidance for practitioners considering starting a minor
      surgery service, outlines the equipment required and describes commonly used
      techniques such as skin biopsy, cryotherapy, excision, electrosurgery and laser
      ablation.

PMID- 22648887
TI  - Causes of first hospitalization among 1121 HIV-infected children: comparison of
      the pre-Pneumocystis jiroveci pneumonia prophylaxis, pre-antiretroviral therapy
      and antiretroviral therapy periods.
AB  - This study identified causes of first hospitalization among perinatally acquired
      HIV-infected children at Chiang Mai University Hospital between 1989 and 2009.
      Data were stratified into three seven-year time periods: pre-Pneumocystis
      jiroveci pneumonia (PJP) prophylaxis, pre-antiretroviral therapy (ART) and ART
      period. Over the 21-year study period, 1121 children were hospitalized. The mean
      age at admission was 2.7 years and had become older over time. Of the 1121
      hospitalization causes, 50.6% were AIDS-defining illnesses (ADIs), 48.1% were non
      AIDS-defining illnesses (NADIs) and 1.3% were related to immune reconstitution
      syndrome. Types of ADIs changed over time: PJP and recurrent Salmonella
      septicaemia decreased, while mycobacterial infection and systemic fungal
      infection increased. For NADIs, bacterial infections, viral infections and
      gastrointestinal problems decreased, but haematological problems increased in the
      third period. Decline in the number of hospitalizations and mortality rate,
      increase in the mean age of hospitalized children, change in the distribution of
      specific illnesses and appearance of immune reconstitution syndrome were observed
      in the ART period.

PMID- 22648888
TI  - Serum and cerebrospinal fluid profiles for syphilis in Thai patients with acute
      ischaemic stroke.
AB  - The diagnosis of neurosyphilis is complicated in elderly patients who have
      cerebrovascular risk factors and present with ischaemic stroke. We performed an
      analysis of serum and cerebrospinal fluid (CSF) profiles for neurosyphilis in
      acute stroke patients, particularly in those with atherosclerotic risk factors.
      In sera, the rapid plasma reagin (RPR) test and Treponema pallidum
      haemagglutination assay (TPHA) were used. In CSF, the RPR and fluorescent
      treponemal antibody-absorption tests were used together with CSF white blood cell
      (WBC) count and protein level. Baseline characteristics, including
      atherosclerotic risk factors, severity of stroke and computed tomography brain
      scan images were collected. Of the total 284 patients, 24 (8.4%) had TPHA
      positive sera, from which 29.2% had a positive CSF for syphilis. Seven stroke
      patients (2.5%), with a mean age of 65.7 years, were diagnosed with symptomatic
      neurosyphilis, and 71% of them had atherosclerotic risk factors. Most symptomatic
      patients (85.7%) had CSF WBCs>20 cells/mm(3), with a mean of 98.6 +/- 136.0
      versus 3.2 +/- 7.3 in non-neurosyphilitic patients (P = 0.0009). Less than 50% of
      the symptomatic patients had CSF protein levels >50 mg/dL, and the protein levels
      of neurosyphilitic and non-neurosyphilitic groups were not significantly
      different, with means of 52.0 +/- 12.9 and 51.8 +/- 15.9 mg/dL, respectively.
      There were no significant differences in age and stroke severity. Interpretation
      of CSF findings, particularly of CSF WBC counts and protein levels, must be
      appropriate to ascertain true symptomatic neurosyphilis cases and to reduce false
      positive diagnoses, particularly in countries with a high prevalence of T.
      pallidum infection.

PMID- 22648889
TI  - Clinical and social determinants of diarrhoeal disease in a rural HIV/AIDS
      clinic, South Africa: a case-control study.
AB  - Diarrhoeal diseases are a common cause of morbidity and are associated with
      mortality in HIV-infected populations. Little is known about the contribution of
      clinical and socio-environmental factors to the risk of diarrhoea in these
      populations in rural sub-Saharan Africa. We conducted a case-control study of
      people attending a rural HIV clinic with an episode of diarrhoea in
      Bushbuckridge, South Africa. Cases were defined as HIV-positive adults with
      symptoms of diarrhoea before or after initiation of antiretroviral therapy (ART).
      Controls without diarrhoea were randomly selected from clinic attendees.
      Structured questionnaires and case-file reviews were undertaken to describe
      clinical and socioenvironmental risk factors. We recruited 103 cases of diarrhoea
      from 121 patients meeting case definitions. Cases were more likely to be women (P
      = 0.013), aged over 45 years (P = 0.002), divorced or separated (P = 0.006), have
      limited formal education (P = 0.003), have inadequate access to sanitation
      facilities (P = 0.045), have water access limited to less than three days per
      week (P = 0.032) and not yet initiated on ART (P < 0.001). In multivariate
      analysis, diarrhoea remained associated with female gender (adjusted odds ratio
      [aOR]: 2.02, 95% CI 1.10-3.73), older age (aOR: 6.31, 95% CI 1.50-26.50), limited
      access to water (aOR: 2.66, 95% CI 1.32-5.35) and pre-ART status (aOR: 5.87, 95%
      CI 3.05-11.27). Clinical and socio-environmental factors are associated with
      occurrence of diarrhoeal disease among rural HIV patients in South Africa.
      Further intervention research is urgently needed, combining community- and clinic
      based approaches, to improve access to water, sanitation and ART for rural areas
      with high HIV prevalence, along with structural interventions to address gender
      inequities.

PMID- 22648890
TI  - Impact of antiretroviral dosing frequency and pill burden on adherence among
      newly diagnosed, antiretroviral-naive HIV patients.
AB  - There are few data on the impact of antiretroviral therapy (ART) regimen factors
      on adherence in ART-naive HIV patients on contemporary once- or twice-daily
      regimens. Ninety-nine newly diagnosed patients in a prospective observational
      cohort study completed a visual analogue scale to assess their ART adherence.
      Adherence by type of ART and dosing frequency were compared by Brown-Mood median
      tests. Participants taking once-daily regimens had higher adherence (n = 70,
      99.5%) compared with participants taking twice-daily regimens (n = 29, 94%; P =
      0.01). Adherence of participants taking the fixed dose combination efavirenz
      emtricitabine-tenofovir (n = 34, 100%) compared with those taking once-daily
      regimens of two or more pills was no different (n = 36, 99.3%; P = 0.34). Among a
      cohort of newly diagnosed ART-naive patients, once-daily dosing of ART resulted
      in higher adherence than twice-daily dosing. Pill burden among once-daily
      regimens did not predict adherence, suggesting that factors other than pill
      burden should drive regimen selection.

PMID- 22648891
TI  - Short-course intravenous aciclovir treatment for cutaneous herpes zoster in
      patients with HIV infection.
AB  - There are no comparative data on the treatment duration of cutaneous herpes
      zoster (HZ) in patients with HIV infection. We retrospectively reviewed all 51
      adult patients with HIV infection presenting with cutaneous HZ in the 15-year
      period 1995-2009 treated with intravenous aciclovir alone. The median CD4 count
      was 297 (range 10-703) cells/mm(3). There were 44 episodes of localized and seven
      episodes of disseminated cutaneous HZ. Patients received a median of nine (range
      3-17) doses of intravenous aciclovir given at a median dose of 6.5 (range 2.9
      10.8) mg/kg eight hourly. One patient (2%) relapsed early and four patients
      (7.8%) relapsed late with further episodes of cutaneous HZ. Seven patients
      (13.7%) developed postherpetic neuralgia. Three days of intravenous aciclovir is
      effective treatment for cutaneous HZ in patients with HIV infection.

PMID- 22648892
TI  - Performance against local service quality indicators: re-setting the indicators.
AB  - Local service quality indicators (SQIs) both for genitourinary medicine and HIV
      were drafted following patient and public involvement in 2009. At that time there
      were few published data to help in setting some of the original SQIs. Our
      clinical performance was audited against these SQIs in 2009 and subsequently re
      audited in 2010 and 2011. The SQIs were revised based upon the results of the
      three audits. This paper attempts to explain the revisions based upon the audits.
      Commissioners are currently working with service providers around the country to
      develop HIV clinical outcome indicators that link payment to performance. It is
      vital to ensure that clinical outcome indicators are set correctly so that they
      are challenging but still achievable. We hope other services may wish to audit
      performance against our revised measures. If such data were to be pooled this
      could provide evidence for more robust benchmarking.

PMID- 22648893
TI  - Therapeutic combination of radiofrequency surgical dissection and oral acitretin
      in the management of perianal Buschke-Lowenstein tumour: a case report.
AB  - Giant condyloma acuminatum (GCA), or Buschke-Lowenstein tumour (BLT), is a rare
      large tumour of the anogenital area. It is caused by human papillomavirus
      genotypes 6 and 11, and it is characterized by aggressive local invasion and
      frequent recurrences after treatment. Treatment of choice is radical excision,
      although chemotherapy and radiation are also used in special cases. We report a
      case of a young man with anogenital GCA, presenting with a large perianal mass
      and pain during defaecation. The patient was treated by surgical removal of
      almost the entirety of the mass, using radiofrequency surgical dissection. The
      concurrent use of oral acitretin for the treatment of erythrodermic psoriasis led
      to elimination of the remaining disease. The patient remains free of disease 26
      months after the end of treatment.

PMID- 22648894
TI  - Calvarial syphilis in an HIV-positive man.
AB  - Bone involvement in secondary and tertiary syphilis is a well-documented but
      unusual phenomenon. We report the case of an atypical presentation of secondary
      syphilis in a 25-year-old HIV-positive man who has sex with men. He presented
      initially with headaches and an unusual calvarial swelling. The skull findings
      were consistent with osteitis and he later developed systemic symptoms. Treponema
      pallidum serology was positive and the lesions and systemic symptoms resolved
      completely after administration of appropriate antibiotic therapy.

PMID- 22648895
TI  - A retained menstrual cup.
AB  - A 20-year-old woman attended a genitourinary clinic with a retained vaginal
      Mooncup that she had inserted the night before. A Mooncup is one type of
      menstrual cup. On speculum examination the device was visualized high in the
      vagina and the cervix appeared firmly lodged within it. The physician experienced
      difficulty in retrieving the cup despite following product instructions. This
      case highlights a new adverse event with an increasingly used sanitation product.
      It is important that clinicians are familiar with the cup, its removal process
      and are able to counsel patients with retained devices on future correct
      placement.

PMID- 22648896
TI  - Immune reconstitution inflammatory syndrome associated with disseminated
      Mycobacterium sherrisii infection.
AB  - Mycobacterium sherrisii is a recently described mycobacterium closely related to
      Mycobacterium simiae. There have been only a few reports of this organism causing
      disease, predominantly in the setting of HIV with severe immunosuppression. We
      report the first case of disseminated M. sherrisii associated with immune
      reconstitution inflammatory syndrome.

PMID- 22648897
TI  - Role of fluconazole in a case of rapid onset ritonavir and inhaled fluticasone
      associated secondary adrenal insufficiency.
AB  - A 52-year-old man with well-controlled HIV infection taking ritonavir and
      increasing doses of inhaled fluticasone for chronic bronchitis developed thrush.
      Within days of discontinuing fluticasone and initiating fluconazole, he presented
      with fatigue, malaise, lower-extremity oedema and orthostasis. Testing confirmed
      exogenous Cushing's syndrome and secondary adrenal insufficiency. Although
      ritonavir-fluticasone interactions have been previously reported as a cause for
      adrenal insufficiency, we propose that fluconazole increased the rapidity of
      onset and severity of symptoms through synergistic inhibition of the adrenal
      axis.

PMID- 22648898
TI  - Reactive arthritis responding to antiretroviral therapy in an HIV-1-infected
      individual.
AB  - Reactive arthritis (ReA) is an autoimmune seronegative spondyloarthropathy that
      occurs in response to a urogenital or enteric infection. Several studies have
      reported a link between ReA and HIV infection. We report a case of an HIV-1
      infected patient diagnosed with a disabling ReA who failed to respond to
      conventional therapy but whose symptoms resolved rapidly after starting
      antiretroviral therapy (ART). Clinicians may not be cognizant to this phenomenon
      and so this case report serves to remind clinicians that initiation of
      antiretroviral therapy should be considered in HIV-infected patients with ReA who
      are refractory to standard therapy.

PMID- 22648899
TI  - A case series of the management of symptomatic azole-resistant candida.
AB  - Patients with symptomatic azole-resistant Candida albicans or non-albicans
      candida are difficult to manage. Treatment is largely anecdotal due to the
      relatively small number of patients. We present six case reports which highlight
      our own observation in clinical practice including four patients who were treated
      successfully with topical amphotericin B/flucytosine vaginal gel for 14 days
      (Stoke-on-Trent formula).

PMID- 22648900
TI  - Ocular cryptococcosis as a presenting manifestation of cryptococcal meningitis in
      a patient with HIV.
AB  - We describe a case of cryptococcal meningitis in a patient known to have HIV who
      presented initially with ocular cryptococcosis. This case highlights to
      clinicians the need to be aware of this association and to carry out relevant
      investigations so as to treat these patients appropriately.

PMID- 22648901
TI  - Tuberculous choroidal granuloma in an HIV-positive patient.
AB  - We report a case of a 34-year-old HIV-positive patient undergoing treatment for
      pulmonary and lymph node Mycobacterium tuberculosis infection, who developed loss
      of vision secondary to a tuberculous choroidal granuloma.

PMID- 22648902
TI  - Performance of methods for handling missing categorical covariate data in
      population pharmacokinetic analyses.
AB  - In population pharmacokinetic analyses, missing categorical data are often
      encountered. We evaluated several methods of performing covariate analyses with
      partially missing categorical covariate data. Missing data methods consisted of
      discarding data (DROP), additional effect parameter for the group with missing
      data (EXTRA), and mixture methods in which the mixing probability was fixed to
      the observed fraction of categories (MIX(obs)), based on the likelihood of the
      concentration data (MIX(conc)), or combined likelihood of observed covariate data
      and concentration data (MIX(joint)). Simulations were implemented to study bias
      and imprecision of the methods in datasets with equal-sized and unbalanced
      category ratios for a binary covariate as well as datasets with non-random
      missingness (MNAR). Additionally, the performance and feasibility of
      implementation was assessed in two real datasets. At either low (10%) or high
      (50%) levels of missingness, all methods performed similarly well. Performance
      was similar for situations with unbalanced datasets (3:1 covariate distribution)
      and balanced datasets. In the MNAR scenario, the MIX methods showed a higher bias
      in the estimation of CL and covariate effect than EXTRA. All methods could be
      applied to real datasets, except DROP. All methods perform similarly at the
      studied levels of missingness, but the DROP and EXTRA methods provided less bias
      than the mixture methods in the case of MNAR. However, EXTRA was associated with
      inflated type I error rates of covariate selection, while DROP handled data
      inefficiently.

PMID- 22648903
TI  - Compartmental tissue distribution of antibody therapeutics: experimental
      approaches and interpretations.
AB  - Monoclonal antibodies have provided many validated and potential new therapeutic
      candidates for various diseases encompassing the realms of neurology,
      ophthalmology, immunology, and especially oncology. The mechanism of action for
      these biological molecules typically involves specific binding to a soluble
      ligand or cell surface protein in order to block or alter a molecular pathway,
      induce a desired cellular response, or deplete a target cell. Many antigens
      reside within the interstitial space, the fluid-filled compartment that lies
      between the outer endothelial vessel wall and the plasma membranes of cells. This
      mini-review examines the concepts relevant to the kinetics and behavior of
      antibodies within the interstitium with a special emphasis on radiometric
      measurement of quantitative pharmacology. Molecular probes are discussed to
      outline chemical techniques, selection criteria, data interpretation, and
      relevance to the study of antibody pharmacokinetics. The importance of studying
      the tissue uptake of antibodies at a compartmental level is highlighted,
      including a brief overview of receptor occupancy and its interpretation in
      radiotracer studies. Experimental methods for measuring the spatial composition
      of tissues are examined in terms of relative vascular, interstitial, and cellular
      volumes using solid tumors as a representative example. Experimental methods and
      physiologically based pharmacokinetic modeling are introduced as distinct
      approaches to distinguish between free and bound fractions of interstitial
      antibody. Overall, the review outlines the available methods for pharmacokinetic
      measurements of antibodies and physiological measurements of the compartments
      that they occupy, while emphasizing that such approaches may not fully capture
      the complexities of dynamic, heterogeneous tumors and other tissues.

PMID- 22648904
TI  - Proton T1 relaxation times of metabolites in human occipital white and gray
      matter at 7 T.
AB  - Proton T1 relaxation times of metabolites in the human brain have not previously
      been published at 7 T. In this study, T1 values of CH3 and CH2 group of N
      acetylaspartate and total creatine as well as nine other brain metabolites were
      measured in occipital white matter and gray matter at 7 T using an inversion
      recovery technique combined with a newly implemented semi-adiabatic spin-echo
      full-intensity acquired localized spectroscopy sequence (echo time = 12 ms). The
      mean T1 values of metabolites in occipital white matter and gray matter ranged
      from 0.9 to 2.2 s. Among them, the T1 of glutathione, scyllo-inositol, taurine,
      phosphorylethanolamine, and N-acetylaspartylglutamate were determined for the
      first time in the human brain. Significant differences in T1 between white matter
      and gray matter were found for water (-28%), total choline (-14%), N
      acetylaspartylglutamate (-29%), N-acetylaspartate (+4%), and glutamate (+8%). An
      increasing trend in T1 was observed when compared with previously reported values
      of N-acetylaspartate (CH3 ), total creatine (CH3 ), and total choline at 3 T.
      However, for N-acetylaspartate (CH3 ), total creatine, and total choline, no
      substantial differences compared to previously reported values at 9.4 T were
      discernible. The T1 values reported here will be useful for the quantification of
      metabolites and signal-to-noise optimization in human brain at 7 T.

PMID- 22648905
TI  - Development of ramified microglia from early macrophages in the zebrafish optic
      tectum.
AB  - Microglia, the resident macrophage precursors of the brain, are necessary for the
      maintenance of tissue homeostasis and activated by a wide range of pathological
      stimuli. They have a key role in immune and inflammatory responses. Early
      microglia stem from primitive macrophages, however the transition from early
      motile forms to the ramified mature resident microglia has not been assayed in
      real time. In order to provide such an assay, we used zebrafish transgenic lines
      in which fluorescent reporter expression is driven by the promoter of macrophage
      expressed gene 1 (mpeg1; Ellet et al. [2011]: Blood 117(4): e49-e56,). This
      enabled the investigation of the development of these cells in live, intact
      larvae. We show that microglia develop from highly motile amoeboid cells that are
      engaged in phagocytosis of apoptotic cell bodies into a microglial cell type that
      rapidly morphs back and forth between amoeboid and ramified morphologies. These
      morphing microglia eventually settle into a typical mature ramified morphology.
      Developing microglia frequently come into contact with blood capillaries in the
      brain, and also frequently contact each other. Up to 10 days postfertilization,
      microglia were observed to undergo symmetric division. In the adult optic tectum,
      the microglia are highly branched, resembling mammalian microglia. In addition,
      the mpeg1 transgene also labeled highly branched cells in the skin overlying the
      optic tectum from 8-9 days postfertilization, which likely represent Langerhans
      cells. Thus, the development of zebrafish microglia and their cellular
      interactions was studied in the intact developing brain in real time and at
      cellular resolution.

PMID- 22648906
TI  - Alterations of the p53 and PIK3CA/AKT/mTOR pathways in angiosarcomas: a pattern
      distinct from other sarcomas with complex genomics.
AB  - BACKGROUND: The p53 and phosphoinositide-3-kinase, catalytic, alpha polypeptide/v
      akt murine thymoma viral oncogene homolog/mechanistic target of rapamycin
      (PIK3CA/AKT/mTOR) pathways frequently are altered in sarcoma with complex
      genomics, such as leiomyosarcoma (LMS) or undifferentiated pleomorphic sarcoma
      (UPS). The scale of genetic abnormalities in these pathways remains unknown in
      angiosarcoma (AS). METHODS: The authors investigated the status of critical genes
      involved in the p53 and PIK3CA/AKT/mTOR pathways in a series of 62 AS. RESULTS:
      The mutation and deletion rates of tumor protein 53 (TP53) were 4% and 0%,
      respectively. Overexpression of p53 was detected by immunohistochemistry in 49%
      of patients and was associated with inferior disease-free survival. Although p14
      inactivation or overexpression of the human murine double minute homolog (HDM2)
      were frequent in LMS and UPS and could substitute for TP53 mutation or deletion,
      such alterations were rare in angiosarcomas. Phosphorylated ribosomal protein S6
      kinase (p-S6K) and/or phosphorylated eukaryotic translation initiation factor 4E
      binding protein 1 (p-4eBP1) overexpression was observed in 42% of patients,
      suggesting frequent activation of the PIK3CA/AKT/mTOR pathway in angiosarcomas.
      Activation was not related to intragenic deletion of phosphatase and tensin
      homolog (PTEN), an aberration that is frequent in LMS and UPS but absent in
      angiosarcomas. CONCLUSIONS: The current results indicated that angiosarcomas
      constitute a distinct subgroup among sarcomas with complex genomics. Although
      TP53 mutation and PTEN deletion are frequent in LMS and UPS, these aberrations
      are rarely involved in the pathogenesis of angiosarcoma.

PMID- 22648907
TI  - Harmonic optical microscopy and fluorescence lifetime imaging platform for
      multimodal imaging.
AB  - In this work, we proposed and built a multimodal optical setup that extends a
      commercially available confocal microscope (Olympus VF300) to include nonlinear
      second harmonic generation (SHG) and third harmonic generation (THG) optical
      (NLO) microscopy and fluorescence lifetime imaging microscopy (FLIM). We explored
      all the flexibility offered by this commercial confocal microscope to include the
      nonlinear microscopy capabilities. The setup allows image acquisition with
      confocal, brightfield, NLO/multiphoton and FLIM imaging. Simultaneously, two
      photon excited fluorescence (TPEF) and SHG are well established in the biomedical
      imaging area, because one can use the same ultrafast laser and detectors set to
      acquire both signals simultaneously. Because the integration with FLIM requires a
      separated modulus, there are fewer reports of TPEF+SHG+FLIM in the literature.
      The lack of reports of a TPEF+SHG+THG+FLIM system is mainly due to difficulties
      with THG because the present NLO laser sources generate THG in an UV wavelength
      range incompatible with microscope optics. In this article, we report the
      development of an easy-to-operate platform capable to perform two-photon
      fluorescence (TPFE), SHG, THG, and FLIM using a single 80 MHz femtosecond
      Ti:sapphire laser source. We described the modifications over the confocal system
      necessary to implement this integration and verified the presence of SHG and THG
      signals by several physical evidences. Finally, we demonstrated the use of this
      integrated system by acquiring images of vegetables and epithelial cancer
      biological samples.

PMID- 22648908
TI  - Polycystic ovaries at ultrasound: normal variant or silent polycystic ovary
      syndrome?
AB  - OBJECTIVE: It is not known whether polycystic ovaries (PCO) are an ovarian
      appearance without pathological meaning or whether they share with polycystic
      ovary syndrome (PCOS) the same ovarian follicle abnormality. There are few
      studies including strictly selected women with PCO but without other criteria of
      PCOS. In order to address these issues, we compared hormonal, metabolic and
      ultrasound parameters obtained from patients with PCO only, patients with PCOS
      and controls. METHODS: This was a comparative analysis including three age
      matched groups of 95 patients, who were included consecutively in a database:
      controls, patients with sonographic PCO but no symptoms (PCO group) and patients
      with PCOS. A clinical examination, fasting serum sampling and pelvic ultrasound
      examination were performed between cycle days 2 and 5 and results were compared
      between groups. RESULTS: The median serum anti-Mullerian hormone (AMH) level in
      the PCO group was intermediate between that in controls and that in the PCOS
      group (33.6 pmol/L, 19.8 pmol/L and 63.3 pmol/L, respectively), the differences
      being significant after adjustment for follicle number (P < 0.05), while the mean
      androgen serum level in the PCO group was similar to that in the control group
      and significantly lower than that in the PCOS group (P < 0.05) (median serum
      testosterone levels: 0.90 nmol/L, 0.79 nmol/L and 1.39 nmol/L; median
      androstenedione levels: 5.25 nmol/L, 4.37 nmol/L and 6.09 nmol/L, respectively).
      Body mass index, waist circumference and insulin levels had no effect on these
      differences. CONCLUSION: PCO is an abnormal condition, affected women showing no
      evidence of hyperandrogenism but having higher AMH serum levels compared with
      controls, suggesting a granulosa cell abnormality in PCO similar to that observed
      in PCOS. The absence of hyperandrogenism in PCO does not seem linked to the
      metabolic status.

PMID- 22648909
TI  - Polymeric fibrous matrices for substrate-mediated human embryonic stem cell
      lineage differentiation.
AB  - Chitosan-based fibrous matrices are prepared to mimic the ECM architecture and
      elucidate substrate-mediated hESC differentiation due to topographical scale and
      anisotropy without exogenic morphogens. Fibrous matrices support fewer
      pluripotent hESCs than films but enable topography-mediated hESC differentiation.
      Matrices composed of 400 nm and 1.1 um diameter fibers support increased
      expression of neural markers indicative of ectodermal commitment while matrices
      of 200 nm diameter fibers increase expression of osteogenic and hepatic markers
      indicative of endodermal and mesodermal commitment. The fibrous-mediated hESC
      differentiation highlights the significant implication of tailored ECM-like
      substrates for hESC-based therapies.

PMID- 22648910
TI  - In vitro and in vivo evaluation of a sulfenamide prodrug of basic metformin.
AB  - In the present study, a previously described sulfenamide prodrug of a basic
      antidiabetic drug, metformin, was evaluated further. This sulfenamide prodrug was
      designed to improve the permeability and consequently the oral absorption and
      bioavailability (F) of the highly water-soluble metformin. Bioactivation of the
      prodrug was mediated by reduced glutathione, but it has been reported that
      sulfenamide prodrugs can also be bioactivated by other endogenous thiols like
      cysteine, and free thiol-containing proteins. Consistent with earlier findings
      for a sulfenamide prodrug of a weakly acid drug, linezolid, the permeability
      studies indicated that the metformin prodrug was also prematurely bioactivated on
      the apical surface of the Caco-2 cell monolayer. Nevertheless, the
      bioavailability of metformin was increased by approximately 25% after oral
      administration of the prodrug in rats, most probably because of better oral
      absorption. This indicates that the sulfenamide prodrug approach may be used to
      improve the moderate oral bioavailability of metformin, which may help to
      decrease the uncomfortable gastrointestinal adverse effects associated with
      metformin therapy as the daily doses of metformin can be reduced. Furthermore,
      the present study confirms that the applicability of the sulfenamide prodrug
      approach can be successfully extended from weak NH acids to very basic guanide
      type drugs.

PMID- 22648911
TI  - Aortic pseudoaneurysm: a rare complication of mediastinoscopy.
AB  - Mediastinoscopy still represents the gold standard in mediastinal lymph node
      staging in patients with lung cancer. It is an invasive procedure, where
      complications are unusual. This case report shows an uncommon complication after
      mediastinoscopy: pseudoaneurysm of the aortic arch and its minimally invasive
      endovascular stenting treatment in order to facilitate the recovery and to allow
      minimal delay to oncological treatment.

PMID- 22648912
TI  - Emergent combined repairs for aortic injury and bowel perforation after blunt
      trauma.
AB  - Traumatic aortic rupture is frequently associated with multi-system injuries and
      is often immediately fatal. Although delayed open repair or endovascular repair
      has been recommended for an acceptable outcome, an emergency operation is
      mandatory for a life-threatening condition. We present here a challenging case of
      survival after immediate, combined repairs for acute aortic injury and bowel
      perforation.

PMID- 22648913
TI  - Comparative in vitro dissolution and in vivo bioequivalence of 2 pentoxifylline
      sustained release formulations.
AB  - Pentoxifylline is a xanthine derivative that is indicated for the treatment of
      patients with intermittent claudication on the basis of chronic occlusive
      arterial disease of the limbs. In the present study, prior to the in vivo study,
      an in vitro comparative dissolution test was performed by the paddle method for 2
      oral sustained release pentoxifylline tablets (400 mg) following the
      bioequivalence guidance of FDA. Metrics of peak exposure (Cmax) and total
      exposure to 24 h (AUC24) were compared using a randomized, single oral, open
      label, 2-period, 2-sequence, 2 treatments crossover study in 24 healthy male
      volunteers under fasted conditions. After an overnight fast, the volunteers
      received 400 mg pentoxifylline and the blood samples were collected over a 24-h
      period following drug administration. Plasma drug concentrations were measured by
      a reverse-phase HPLC method with ultraviolet detection. In vitro dissolution
      tests requirements were met by both formulations. Observed exposure metrics for
      test and reference products were 140.6+/-51.5 and 132.6+/-48.5 ng/ml for Cmax and
      986.4+/-350.7 and 1 035.8+/-350.3 ng.h/ml for AUC0-24 respectively. The
      confidence intervals (90%) around ratios (test/reference) of least squares means
      derived from logarithmic transformed exposure metrics were 0.9912-1.1564% for
      Cmax and 0.8886-1.0535% for AUC0-24. Therefore it can be concluded that both
      products are bioequivalent in terms of peak and total exposure and therefore
      interchangeable.

PMID- 22648914
TI  - A simplified homology-model builder toward highly protein-like structures: an
      inspection of restraining potentials.
AB  - A homology model builder using simple restraining potentials based on spline
      interpolated quadratic functions is developed and interfaced with CHARMM package.
      The continuity and stability of the potential function were validated, and the
      parameters were optimized using the CASP7 targets. The performance of the model
      builder was benchmarked to the Modeller program using the template-based modeling
      targets in CASP9. The benchmark results show that, while our builder yields the
      structures with slightly lower packing, backbone, and template modeling scores,
      our models show much better protein-like scores in terms of normalized discrete
      optimized protein energy, dipolar distance-scaled finite-ideal gas reference,
      Molprobity clash, Ramachandran appearance Z-score, and rotamer Z-score. As our
      model builder is interfaced with CHARMM, it is advantageous to directly use other
      CHARMM functionality and energy functions to refine the model structures or to
      use the models for other computational studies using CHARMM.

PMID- 22648915
TI  - Multimodality imaging of a papillary fibroelastoma of the mitral valve.

PMID- 22648916
TI  - Long-term biventricular support with rotary blood pumps: prospects and pitfalls.

PMID- 22648917
TI  - Unruptured sinus of Valsalva aneurysm displacing the right atrium.

PMID- 22648918
TI  - How well calibrated is EuroSCORE II?

PMID- 22648919
TI  - Not just a toy: accidental cardiac injury from an air rifle.

PMID- 22648921
TI  - Time to end the disparity of training in Europe.

PMID- 22648920
TI  - Transapical aortic valve implantation: mid-term outcome from the SOURCE registry.
AB  - OBJECTIVES: Transapical (TA) aortic valve implantation using the Edwards SAPIEN
      bioprosthesis was commercially introduced in Europe in January 2008. Limited data
      on the mid-term results are available. METHODS: Using data from the SOURCE
      Registry (largest consecutive cohort treated using Edwards SAPIEN bioprosthesis
      in Europe), we report on the mid-term results (>=30 days-2 years) of TA patients.
      RESULTS: Between November 2007 and December 2009, a total of 1387 patients from
      38 European centres underwent TA aortic valve implantation. The mean follow-up is
      14.9 months, with 1004 patients who completed 1 year and 464 patients who
      completed the 2-year follow-up. The mean age of patients was 80.6 +/- 7.1 years
      with a logistic-EuroSCORE of 27.6%. The main co-morbidities were coronary artery
      disease (55.8%), previous bypass grafting (25.5%), porcelain aorta (10.2%),
      previous stroke (6.5%) and peripheral vascular disease (26.4%). A total of 840
      patients (60.6%) received a 26 mm and 535 (38.6%) a 23 mm Edwards SAPIEN
      bioprosthesis. Survivals at 30 days, 1 year and 2 years were 88.7, 73.8 and
      65.1%, respectively. Causes of the 276 deaths observed between >30 days and 2
      year follow-up were cardiac in 86 patients (31.2%), non-cardiac in 142 (51.4%)
      and unknown in 48 (17.4%). Cardiac causes of death included heart failure
      (33.7%), sudden cardiac death (33.7%), myocardial infarct (8.1%), endocarditis
      (5.8%) and others (18.6%). Non-cardiac deaths were related to pulmonary disease
      (21.1%), cancer (12.7%), renal failure (11.3%), stroke (10.6%), gastrointestinal
      disease (7.7%) and others (36.6%). Using univariable and multivariable analyses,
      logistic EuroSCORE, renal insufficiency and liver diseases were identified as
      independent predictors of 2-year mortality. CONCLUSIONS: These results
      demonstrate that in elderly patients with severe co-morbidities, TA aortic valve
      implantation results in excellent mid-term results. Causes of death during the
      mid-term follow-up are mainly non-cardiac and related to co-morbidities.

PMID- 22648922
TI  - A moderate-sized mass diagnosed as a lipoma arising from the adventitia of the
      ascending aorta.

PMID- 22648924
TI  - Direct transapical aortic valve implantation: a modified transcatheter approach
      avoiding balloon predilatation.
AB  - Transcatheter aortic valve implantation (T-AVI) is an accepted alternative
      treatment option for patients with aortic stenosis seen inoperable or high risk
      for aortic valve (AV) replacement. However, a significant risk of stroke and
      cerebrovascular complications raises concern. Cerebral embolizations during T-AVI
      are frequent and recent data demonstrates that balloon aortic valvuloplasty
      during transcatheter procedures causes nearly as many high-intensity transient
      signals and microembolic signals as the deployment of the transcatheter heart
      valve itself. Omitting predilatation, therefore, may reduce the incidence of
      microembolizations and a possible stroke. We have developed a novel technique of
      'Direct Transapical Aortic Valve Implantation', which enables surgeons to avoid
      predilatation of the native AV. So far, a total of six consecutive patients were
      treated using the Edwards SAPIEN XTTM transcatheter heart valve (Edwards
      Lifesciences, Irvine, CA, USA). Compared with conventional transapical
      implantations using the same device, procedure time was shorter, less contrast
      used and duration of fluoroscopy reduced. Procedural success was achieved in all
      patients, and all were discharged home without greater than or equal to moderate
      paravalvular leakage observed. Direct transapical implantation is technically
      safe and effective, with shorter radiation/procedure times. It is the next
      logical step in the direction of a full percutaneous transapical approach and
      potentially can result in reduced microembolizations.

PMID- 22648923
TI  - Omentoplasty in preventing anastomotic leakage of oesophagogastrostomy following
      radical oesophagectomy with three-field lymphadenectomy.
AB  - OBJECTIVES: Anastomotic leakage is a major cause of mortality in oesophageal
      surgery. Whether omentoplasty after oesophagogastrostomy could reduce anastomotic
      leakage is still controversial. The aim of this study is to investigate the
      function of omentoplasty to reinforce cervical oesophagogastrostomy after radical
      oesophagectomy with three-field lymphadenectomy. METHODS: A total of 184 patients
      who underwent radical oesophagectomy with three-field lymphadenectomy took part
      in this prospective study. Patients were randomized to receive either the
      omentoplasty or non-omentoplasty. In the omentoplasty group, the omentum was
      wrapped around the oesophagogastric anastomosis after oesophagogastrostomy. Age,
      gender, location of carcinoma, stage, body mass index, diabetes, coronary artery
      disease, peripheral vascular disease and performance of omentoplasty were
      recorded. The anastomotic leakage and stricture and recurrence site were followed
      up for three years after the operation. RESULTS: The two groups were comparable
      in terms of age, gender, location of carcinoma, stage, body mass index, diabetes,
      coronary artery disease and peripheral vascular disease (P > 0.05). In contrast
      to the non-omentoplasty group with a postoperative anastomotic leakage rate of
      9.8%, the omentoplasty subjects demonstrated a significantly lower rate of 3.3%
      (P < 0.05). No lethal leakage was found in the omentoplasty group, while two non
      omentoplasty patients developed incurable empyema and mediastinitis due to
      leakage and ultimately died. The rate of incidence of anastomotic stricture in
      the omentoplasty and non-omentoplasty groups were 4.3% and 2.2% respectively. Of
      the five cases of death during the hospital stay, two were found in the
      omentoplasty group and three in non-omentoplasty. There was no significant
      difference of lethal leakage, stricture and death rate between the two groups (P
      > 0.05). The hospital stay was significantly longer for non-omentoplasty
      patients, compared with that for the omentoplasty subjects (P < 0.05). Tumour
      recurrence in lymphatic- or haematogenous metastasis was similar in both groups
      (P > 0.05). CONCLUSION: Omentoplasty may prevent anastomotic leakage of
      oesophagogastrostomy following radical oesophagectomy with three-field
      lymphadenectomy.

PMID- 22648925
TI  - Preservation solution supplemented with biliverdin prevents lung cold
      ischaemia/reperfusion injury.
AB  - OBJECTIVES: Biliverdin (BV), one of the byproducts of heme catalysis through the
      heme oxygenase system, is a known scavenger of the reactive oxygen species. We
      hypothesized that adding BV to the perfusate and cold storage solution could
      protect rat lung grafts from oxidative injuries via its antioxidant efficacies.
      METHODS: Orthotopic left lung transplantation was performed in a syngenic Lewis
      to-Lewis rat combination under 100% oxygen. Grafts were preserved in low
      potassium dextran (LPD; Perfadex) at 4 degrees C for 6 h with or without
      supplementation of 1 or 10 MUM of BV into LPD. RESULTS: Prolonged cold storage
      and reperfusion resulted in a considerable deterioration of graft functions
      associated with massive apoptosis in the grafts after reperfusion. The untreated
      grafts exhibited the early up-regulations of mRNA for inflammatory mediators and
      an increase in a marker of lipid peroxidation, showing oxidative injuries.
      Although BV supplementation of LPD at a lower concentration (1 MUM) did not
      improve the graft gas exchange, the grafts treated with BV (10 MUM) showed a
      significant improvement of oxygenation and less inflammatory responses as well as
      reduced lipid peroxidation and apoptosis. Although the rapid activations of
      mitogen-activated protein kinases (MAPKs) were seen 30 min after reperfusion in
      the grafts stored in control LPD, BV treatment significantly reduced
      phosphorylated-MAPK protein expression. CONCLUSIONS: This study demonstrates that
      the exposure of the lung grafts to BV during cold storage can impart potent
      cytoprotective effects to lung cold ischaemia/reperfusion injury and
      significantly improve the lung graft function following extended cold
      preservation and transplantation by the mechanism of a reduction in oxidative
      injury and following inflammatory events.

PMID- 22648926
TI  - Cold reperfusion before rewarming reduces neurological events after deep
      hypothermic circulatory arrest.
AB  - OBJECTIVES: To identify a safety threshold of deep hypothermic circulatory arrest
      (DHCA) duration; to determine which protection offers the best outcome and
      whether a 10-min period of cold perfusion (20 degrees C) preceding rewarming can
      reduce neurological events (NE). METHODS: From January 1988 to April 2009, 456
      patients underwent aortic surgery using DHCA: for chronic disease in 239 and
      acute in 217. Cerebral protection was obtained by straight DHCA (sDHCA) in 69
      cases, retrograde perfusion (RCP) in 198 and antegrade perfusion (ACP) in 189. In
      247 subjects, a 10-min period of cold perfusion (20 degrees C) preceded
      rewarming; in 209 rewarming was restarted without this preliminary. RESULTS:
      Fifty-eight patients (13%) experienced NE. Twenty-two (5%) suffered temporary
      neurological dysfunction (TND) and 36 (8%) suffered stroke. DHCA duration >30 min
      was predictive for higher rate of NE (25.2% vs. 2.0%, P 0.001); after this value,
      only ACP was able to reduce incidence of NE (16.5% vs. 30.5%, P = 0.035). Cold
      reperfusion before rewarming significantly reduced incidence of NE (7.7% vs.
      18.7%, P < 0.001) and extended the safe period to 40 min. Thirty-day mortality
      was 16.0%. Predictors of higher early mortality were acute aortic disease, longer
      DHCA, lack of ACP or prompt rewarming when DHCA >30 min and postoperative stroke.
      CONCLUSIONS: sDHCA remains a safe and easy tool for cerebral protection when DHCA
      duration is expected to be less than 30 min. When aortic surgery requires a
      longer period, ACP should be instituted. Before rewarming, a 10-min period of
      cold perfusion significantly reduces incidence of NE.

PMID- 22648927
TI  - Single step optical fabrication of a DFB laser device in fluorescent azobenzene
      containing materials.
AB  - Distributed feedback (DFB) lasers are produced directly in fluorescent azobenzene
      containing materials using a single holographic optical step. Surface relief
      grating capable of producing images in fluorescence microscopy can be
      holographically formed in a number of materials.

PMID- 22648928
TI  - Saturation-recovery metabolic-exchange rate imaging with hyperpolarized [1-13C]
      pyruvate using spectral-spatial excitation.
AB  - Within the last decade hyperpolarized [1-13C] pyruvate chemical-shift imaging has
      demonstrated impressive potential for metabolic MR imaging for a wide range of
      applications in oncology, cardiology, and neurology. In this work, a highly
      efficient pulse sequence is described for time-resolved, multislice chemical
      shift imaging of the injected substrate and obtained downstream metabolites.
      Using spectral-spatial excitation in combination with single-shot spiral data
      acquisition, the overall encoding is evenly distributed between excitation and
      signal reception, allowing the encoding of one full two-dimensional metabolite
      image per excitation. The signal-to-noise ratio can be flexibly adjusted and
      optimized using lower flip angles for the pyruvate substrate and larger ones for
      the downstream metabolites. Selectively adjusting the excitation of the down
      stream metabolites to 90 degrees  leads to a so-called "saturation-recovery"
      scheme with the detected signal content being determined by forward conversion of
      the available pyruvate. In case of repetitive excitations, the polarization is
      preserved using smaller flip angles for pyruvate. Metabolic exchange rates are
      determined spatially resolved from the metabolite images using a simplified two
      site exchange model. This novel contrast is an important step toward more
      quantitative metabolic imaging. Goal of this work was to derive, analyze, and
      implement this "saturation-recovery metabolic exchange rate imaging" and
      demonstrate its capabilities in four rats bearing subcutaneous tumors.

PMID- 22648929
TI  - Toll-like receptor-4 agonist inhibits motility and invasion of hepatoblastoma
      HepG2 cells in vitro.
AB  - BACKGROUND: Expression of toll-like receptor-4 (TLR4) on tumor cells is known to
      mediate innate immune responses that influence tumor cell growth and migration.
      This study aimed to characterize TLR4 expression and elucidate its functional
      significance in human hepatoblastoma (HB) cells. PROCEDURE: Immunohistochemistry
      (IHC) was used to determine TLR4 expression level and its distribution pattern in
      HB liver tissues. Transcripts of tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-8, matrix metalloproteinase (MMP)-2, MMP-13, tissue inhibitor of
      metalloproteinases (TIMP)-1, and TIMP-2 in HB HepG2 cells with lipopolysacharide
      (LPS) treatment were measured by quantitative PCR. Soluble cytokines and peptides
      in conditioned media were measured by ELISA. MMP-2 activity was determined by
      using gelatin zymography. Cell motility and invasiveness was determined using
      wound healing migration and Matrigel invasion assays, respectively. RESULTS: TLR4
      IHC staining demonstrated that TLR4 overexpression in HB liver tissues
      dramatically vanished after chemotherapy. In vitro study using an HB cell line,
      HepG2, showed that TLR4 agonist, LPS, significantly decreased transcripts of IL-8
      and TNF-alpha, but did not affect MMP-13 mRNA level. By contrast, LPS only down
      regulated IL-8 production and MMP-2 gelatinolytic activity. The latter might be
      in part due to the increased levels of MMP-2/TIMP-2 complex in conditioned media,
      thus leading to the decreased motility and invasiveness of HepG2 cells.
      CONCLUSIONS: HB cells overexpress TLR4, whereas TLR4 agonistic treatment inhibits
      migration and invasion of HB HepG2 cells. These findings suggest that TLR4
      signaling pathway is a potential therapeutic target for control of HB tumor
      progression.

PMID- 22648930
TI  - Lack of Tir ubiquitylation contributes to enteropathogenic E. coli remaining
      extracellular during nonphagocytic cell infections.
AB  - Enteropathogenic Escherichia coli (EPEC) is an extracellular pathogen that alters
      many host subcellular components during its infectious processes. We have
      previously shown that EPEC hijacks a large assortment of host cell endocytic
      components and uses these proteins to form protruding structures called
      "pedestals" rather than triggering internalization of the bacteria. Other
      invasive pathogens that also recruit similar endocytic components have been shown
      to enter their host cells on the ubiquitylation of their host cell receptors.
      Therefore, we hypothesize that EPEC remains extracellular by maintaining its
      receptor, translocated intimin receptor (Tir), in an unubiquitylated state. Using
      immunoprecipitation-Western blots, we demonstrate no association of ubiquitin
      with Tir. To further elucidate the effect Tir ubiquitylation would have on EPEC
      during their infections, we engineered Tir-ubiquitin fusion constructs, expressed
      them in host epithelial cells, and infected them with Deltatir EPEC. We found
      these cells induced a significant increase in EPEC invasion as compared with
      cells that expressed the Tir construct that lacked ubiquitin conjugation. Our
      results indicate that the lack of EPEC receptor ubiquitylation is a contributing
      factor that these microbes use to prevent their internalization into epithelial
      cells.

PMID- 22648931
TI  - Oral tissue response to ovine grafting biomaterial: morphological and
      morphometric study using scanning electron and light microscopy tissue response
      to ovine grafting biomaterial.
AB  - OBJECTIVE: To evaluate the oral tissue response to an experimental particle ovine
      biomaterial by scanning electron microscopy (SEM) and light microscopy (LM).
      MATERIAL AND METHODS: Forty-eight rats had surgical periodontal defects treated
      with either blood clotting (control), bovine biomaterialTM (B), or an
      experimental ovine biomaterial (O). Data from SEM analysis (defect exposure, root
      surface exposure, diameter of matrix fibers and bundles, and globuli areas; n =
      5) were applied to Shapiro-Wilk, Kruskal-Wallis, and Dunn's test, whereas LM
      analysis (tissue cicatrization characteristics and diameter defect; n = 3) had
      data applied to two-way analysis of variance. Animals were monitored for 1 and 3
      weeks. RESULTS: By SEM, the O samples showed significant differences from B and C
      in the area of defect exposure (H(2,15) = 8.66; P < 0.05). In both periods, O and
      B samples showed similar results for matrix fiber diameters, differently than C
      samples (H(2,15) = 14.0; P < 0.05). All other SEM variables were considered
      equivalent among the groups (P > 0.05). Under LM, an acute and chronic
      granulomatous inflammation was seen in the presence of both biomaterials (B and
      O, 1 week); both the control and the ovine grafting samples showed mature bone in
      the repair site (3 weeks); the defect diameter showed similar values among
      groups, at both monitoring periods (F(2,12) = 1.0401; P > 0.05). CONCLUSION: The
      ovine particles of this study showed a favorable response to oral tissue repair,
      demonstrating to be a potential source for the development of bone grafting
      biomaterials.

PMID- 22648932
TI  - Does levator trauma 'heal'?
AB  - OBJECTIVE: To evaluate if pregnancy- and delivery-related changes to levator
      morphology and distensibility regress with time. METHODS: 488 nulliparous
      pregnant women, recruited between 36 and 38 weeks' gestation, were invited for
      assessment at 3-6 months and again at 2-3 years postpartum. All underwent an
      interview and four-dimensional translabial ultrasound examination. Hiatal
      morphometry and bladder neck descent (BND) were determined and compared between
      the two postpartum visits. RESULTS: 367 participants returned for assessment at
      4.1 (interquartile range (IQR), 3.7-5.0) months and 161 returned at 2.6 (IQR, 2.0
      3.1) years, allowing a groupwise comparison. There was no significant difference
      in hiatal area (22 vs 22 cm(2), P = 0.95) or BND on Valsalva maneuver (26.3 vs
      25.5 mm, P = 0.49). Pairwise comparison in women who had attended both postpartum
      appointments without second births (n = 77), separately for those who had a
      cesarean section (n = 24) and those who had a vaginal delivery (n = 53)
      originally, showed no significant changes, except a reduction in BND (31.2 vs
      28.3 mm, P = 0.025) in those who had delivered vaginally. Two women out of 12
      diagnosed with a levator avulsion at 3-6 months showed obvious anatomical
      improvement on translabial ultrasound at 2-3 years. CONCLUSIONS: We found no
      evidence of regression or healing of pregnancy- and delivery-related changes to
      levator distensibility on comparing imaging data obtained at 3-6 months and 2-3
      years postpartum. However, we documented anatomical improvement on translabial
      ultrasound at the second postpartum visit in two women diagnosed with levator
      avulsion at 3-6 months postpartum.

PMID- 22648933
TI  - Purine-rich foods intake and recurrent gout attacks.
AB  - OBJECTIVE: To examine and quantify the relation between purine intake and the
      risk of recurrent gout attacks among gout patients. METHODS: The authors
      conducted a case-crossover study to examine associations of a set of putative
      risk factors with recurrent gout attacks. Individuals with gout were
      prospectively recruited and followed online for 1 year. Participants were asked
      about the following information when experiencing a gout attack: the onset date
      of the gout attack, clinical symptoms and signs, medications (including antigout
      medications), and presence of potential risk factors (including daily intake of
      various purine-containing food items) during the 2-day period prior to the gout
      attack. The same exposure information was also assessed over 2-day control
      periods. RESULTS: This study included 633 participants with gout. Compared with
      the lowest quintile of total purine intake over a 2-day period, OR of recurrent
      gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing
      quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and
      2.41 for increasing quintiles of purine intake from animal sources (p for trend
      <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively.
      The effect of purine intake persisted across subgroups by sex, use of alcohol,
      diuretics, allopurinol, NSAIDs and colchicine. CONCLUSIONS: The study findings
      suggest that acute purine intake increases the risk of recurrent gout attacks by
      almost fivefold among gout patients. Avoiding or reducing amount of purine-rich
      foods intake, especially of animal origin, may help reduce the risk of gout
      attacks.

PMID- 22648936
TI  - Hereditary pheochromocytoma and paraganglioma.
AB  - Hereditary pheochromocytomas (pheo) and paragangliomas (pgl) are caused by
      identifiable germline mutations. The previously well-known associated syndromes
      include neurofibromatosis type 1, multiple endocrine neoplasia 2 A and B, and von
      Hippel-Lindau syndrome. Newly discovered mutations in the succinate dehydrogenase
      gene complex have been identified as a cause of inherited pgls and pheos. It is
      now clear that up to 30% of patients presenting with sporadic pheos/pgls harbor a
      recognizable germline mutation, and therefore directed genetic testing is
      recommended for many of these patients.

PMID- 22648935
TI  - Release profiles of tricalcium phosphate nanoparticles from poly(L-lactic acid)
      electrospun scaffolds with single component, core-sheath, or porous fiber
      morphologies: effects on hASC viability and osteogenic differentiation.
AB  - Functional PLA scaffolds are created with single component, core-sheath, or
      porous fiber morphology and doped with TCP nanoparticles to study the release
      profiles for use in bone tissue engineering applications. Pharmacokinetic
      analyses are performed for the three different nanofibrous structures after
      doping with TCP. Results indicate that single component and porous fiber
      scaffolds exhibit an initial-burst release profile whereas core-sheath fibers
      show a steady release. All scaffolds are then seeded with human adipose-derived
      stem cells (hASC), which remain viable and continue proliferation on all
      nanofibrous morphologies for up to 21 d. Osteogenic differentiation of hASC and
      cell-mediated calcium accretion are largest on porous fibers.

PMID- 22648937
TI  - Near-infrared light-responsive intracellular drug and siRNA release using au
      nanoensembles with oligonucleotide-capped silica shell.
AB  - Taking advantage of the character of Au nanorods (NRs) to absorb NIR light, a NIR
      responsive oligonucleotide-gated ensemble is developed to perform intracellular
      drug delivery. Using an oligonucleotide bio-gate enables siRNA release into cells
      for translational regulation as well as cytotoxicity in anti-cancer drug
      delivery.

PMID- 22648938
TI  - Current issues and controversies in the classification of pediatric
      hepatocellular tumors.
AB  - Systematic histopathologic examination of hepatoblastoma specimens from patients
      enrolled in therapeutic protocols has allowed the identification of clinically
      relevant histologic subtypes that are being incorporated into risk stratification
      systems. Genetic and molecular studies have documented recurrent chromosomal
      abnormalities and aberrant activation of developmental, and oncogenic signaling
      pathways in hepatoblastoma. Molecular profiling has also identified molecular
      subclasses and gene signatures that could be used to stratify hepatoblastoma
      patients. Future international collaboration is needed to develop consensus
      pathology classifications, and to progressively incorporate genetic and molecular
      biomarkers into therapeutic pediatric liver tumors protocols.

PMID- 22648939
TI  - Power of single- vs. multi-marker tests of association.
AB  - Current genome-wide association studies still heavily rely on a single-marker
      strategy, in which each single nucleotide polymorphism (SNP) is tested
      individually for association with a phenotype. Although methods and software
      packages that consider multimarker models have become available, they have been
      slow to become widely adopted and their efficacy in real data analysis is often
      questioned. Based on conducting extensive simulations, here we endeavor to
      provide more insights into the performance of simple multimarker association
      tests as compared to single-marker tests. The results reveal the power advantage
      as well as disadvantage of the two- vs. the single-marker test. Power
      differentials depend on the correlation structure among tag SNPs, as well as that
      between tag SNPs and causal variants. A two-marker test has relatively better
      performance than single-marker tests when the correlation of the two adjacent
      markers is high. However, using HapMap data, two-marker tests tended to have a
      greater chance of being less powerful than single-marker tests, due to
      constraints on the number of actual possible haplotypes in the HapMap data. Yet,
      the average power difference was small whenever the one-marker test is more
      powerful, while there were many situations where the two-marker test can be much
      more powerful. These findings can be useful to guide analyses of future studies.

PMID- 22648940
TI  - Fine-tuning our personalized medicine for otitis media.

PMID- 22648942
TI  - Benign paroxysmal positional vertigo without nystgamus.

PMID- 22648947
TI  - Ultrastructure of differentiating oocytes and vitellogenesis in the giant
      freshwater prawn, Macrobrachium rosenbergii (De Man).
AB  - The ultrastructure of oogenesis in Macrobrachium rosenbergii, with reference to
      vitellogenesis, has not been reported. We used light and electron microscopy, as
      well as vitellin (Vn) purification and antibody production, to study the temporal
      and spatial production of Vn in the ovary by immunofluorescence. Histologically,
      the ovary is subdivided into cone-shaped ovarian pouches with a central core
      containing layers of oogonia. These divide to produce oocytes that migrate
      outwardly and differentiate into mature oocytes. During the course of
      differentiation, oocytes undergo modifications, including the rearrangement of
      nuclear chromatin, the accumulation of ribosomes, rough endoplasmic reticulum
      (RER), and lipid, and the formation of secretory and yolk granules, resulting in
      four stages. Ultrastructurally, early previtellogenic oocytes (Oc(1)) are
      characterized by the accumulation of new ribosomal aggregates, translocated from
      the nucleus. Late previtellogenic oocytes (Oc(2)) show nuclear heterochromatin
      with a "clock face" pattern, the presence of RER, and three types of secretory
      granules. Follicular cells occupy the intercellular spaces and surround the
      Oc(2). Early vitellogenic oocytes (Oc(3)) are larger, with nuclei containing
      predominantly decondensed euchromatin, and cytoplasm with yolk and secretory
      granules, and few lipid droplets. Late vitellogenic oocytes (Oc(4)) are
      characterized by completely euchromatic nuclei, an indistinct plasma membrane,
      yolk platelets and secretory granules, and abundant lipid. Vitellogenin (Vg) in
      ovaries of M. rosenbergii consist of two main bands at MW 90 and 102 kDa. Our
      data indicates that Vn is present, and probably synthesized in Oc(3) and Oc(4),
      but there may be some undetected exogenous Vg production.

PMID- 22648948
TI  - OSR1-sensitive regulation of Na+/H+ exchanger activity in dendritic cells.
AB  - The oxidative stress-responsive kinase 1 (OSR1) is activated by WNK (with no K
      kinases) and in turn stimulates the thiazide-sensitive Na-Cl cotransporter (NCC)
      and the furosemide-sensitive Na-K-2Cl cotransporter (NKCC), thus contributing to
      transport and cell volume regulation. Little is known about extrarenal functions
      of OSR1. The present study analyzed the impact of decreased OSR1 activity on the
      function of dendritic cells (DCs), antigen-presenting cells linking innate and
      adaptive immunity. DCs were cultured from bone marrow of heterozygous WNK
      resistant OSR1 knockin mice (osr(KI)) and wild-type mice (osr(WT)). Cell volume
      was estimated from forward scatter in FACS analysis, ROS production from 2',7'
      dichlorodihydrofluorescein-diacetate fluorescence, cytosolic pH (pH(i)) from
      2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein fluorescence, and
      Na(+)/H(+) exchanger activity from Na(+)-dependent realkalinization following
      ammonium pulse and migration utilizing transwell chambers. DCs expressed WNK1,
      WNK3, NCC, NKCC1, and OSR1. Phosphorylated NKCC1 was reduced in osr(KI) DCs. Cell
      volume and pH(i) were similar in osr(KI) and osr(WT) DCs, but Na(+)/H(+)
      exchanger activity and ROS production were higher in osr(KI) than in osr(WT) DCs.
      Before LPS treatment, migration was similar in osr(KI) and osr(WT) DCs. LPS (1
      MUg/ml), however, increased migration of osr(WT) DCs but not of osr(KI) DCs.
      Na(+)/H(+) exchanger 1 inhibitor cariporide (10 MUM) decreased cell volume,
      intracellular reactive oxygen species (ROS) formation, Na(+)/H(+) exchanger
      activity, and pH(i) to a greater extent in osr(KI) than in osr(WT) DCs. LPS
      increased cell volume, Na(+)/H(+) exchanger activity, and ROS formation in
      osr(WT) DCs but not in osr(KI) DCs and blunted the difference between osr(KI) and
      osr(WT) DCs. Na(+)/H(+) exchanger activity in osr(WT) DCs was increased by the
      NKCC1 inhibitor furosemide (100 nM) to values similar to those in osr(KI) DCs.
      Oxidative stress (10 MUM tert-butyl-hydroperoxide) increased Na(+)/H(+) exchanger
      activity in osr(WT) DCs but not in osr(KI) DCs and reversed the difference
      between genotypes. Cariporide virtually abrogated Na(+)/H(+) exchanger activity
      in both genotypes and blunted LPS-induced cell swelling and ROS formation in
      osr(WT) mice. In conclusion, partial OSR1 deficiency influences Na(+)/H(+)
      exchanger activity, ROS formation, and migration of dendritic cells.

PMID- 22648949
TI  - NOX2-dependent ROS is required for HDAC5 nuclear efflux and contributes to HDAC4
      nuclear efflux during intense repetitive activity of fast skeletal muscle fibers.
AB  - Reactive oxygen species (ROS) have been linked to oxidation and nuclear efflux of
      class IIa histone deacetylase 4 (HDAC4) in cardiac muscle. Here we use HDAC-GFP
      fusion proteins expressed in isolated adult mouse flexor digitorum brevis muscle
      fibers to study ROS mediation of HDAC localization in skeletal muscle. H(2)O(2)
      causes nuclear efflux of HDAC4-GFP or HDAC5-GFP, which is blocked by the ROS
      scavenger N-acetyl-l-cysteine (NAC). Repetitive stimulation with 100-ms trains at
      50 Hz, 2/s ("50-Hz trains") increased ROS production and caused HDAC4-GFP or
      HDAC5-GFP nuclear efflux. During 50-Hz trains, HDAC5-GFP nuclear efflux was
      completely blocked by NAC, but HDAC4-GFP nuclear efflux was only partially
      blocked by NAC and partially blocked by the calcium-dependent protein kinase
      (CaMK) inhibitor KN-62. Thus, during intense activity both ROS and CaMK play
      roles in nuclear efflux of HDAC4, but only ROS mediates HDAC5 nuclear efflux. The
      10-Hz continuous stimulation did not increase the rate of ROS production and did
      not cause HDAC5-GFP nuclear efflux but promoted HDAC4-GFP nuclear efflux that was
      sensitive to KN-62 but not NAC and thus mediated by CaMK but not by ROS. Fibers
      from NOX2 knockout mice lacked ROS production and ROS-dependent nuclear efflux of
      HDAC5-GFP or HDAC4-GFP during 50-Hz trains but had unmodified Ca(2+) transients.
      Our results demonstrate that ROS generated by NOX2 could play important roles in
      muscle remodeling due to intense muscle activity and that the nuclear effluxes of
      HDAC4 and HDAC5 are differentially regulated by Ca(2+) and ROS during muscle
      activity.

PMID- 22648951
TI  - Tracking stars: automated two-dimensional analysis of Ca2+ events. Focus on
      "Automated region of interest analysis of dynamic Ca2+ signals in image
      sequences".

PMID- 22648950
TI  - Cyclic AMP-induced K+ secretion occurs independently of Cl- secretion in rat
      distal colon.
AB  - cAMP induces both active Cl(-) and active K(+) secretion in mammalian colon. It
      is generally assumed that a mechanism for K(+) exit is essential to maintain
      cells in the hyperpolarized state, thus favoring a sustained Cl(-) secretion.
      Both Kcnn4c and Kcnma1 channels are located in colon, and this study addressed
      the questions of whether Kcnn4c and/or Kcnma1 channels mediate cAMP-induced K(+)
      secretion and whether cAMP-induced K(+) secretion provides the driving force for
      Cl(-) secretion. Forskolin (FSK)-enhanced short-circuit current (indicator of net
      electrogenic ion transport) and K(+) fluxes were measured simultaneously in
      colonic mucosa under voltage-clamp conditions. Mucosal Na(+) orthovanadate (P
      type ATPase inhibitor) inhibited active K(+) absorption normally present in rat
      distal colon. In the presence of mucosal Na(+) orthovanadate, serosal FSK induced
      both K(+) and Cl(-) secretion. FSK-induced K(+) secretion was 1) not inhibited by
      either mucosal or serosal 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM
      34; a Kcnn4 channel blocker), 2) inhibited (92%) by mucosal iberiotoxin (Kcnma1
      channel blocker), and 3) not affected by mucosal cystic fibrosis transmembrane
      conductance regulator inhibitor (CFTR(inh)-172). By contrast, FSK-induced Cl(-)
      secretion was 1) completely inhibited by serosal TRAM-34, 2) not inhibited by
      either mucosal or serosal iberiotoxin, and 3) completely inhibited by mucosal
      CFTR(inh)-172. These results indicate that cAMP-induced colonic K(+) secretion is
      mediated via Kcnma1 channels located in the apical membrane and most likely
      contributes to stool K(+) losses in secretory diarrhea. On the other hand, cAMP
      induced colonic Cl(-) secretion requires the activity of Kcnn4b channels located
      in the basolateral membrane and is not dependent on the concurrent activation of
      apical Kcnma1 channels.

PMID- 22648952
TI  - VDR and CYP27B1 are expressed in C2C12 cells and regenerating skeletal muscle:
      potential role in suppression of myoblast proliferation.
AB  - 1alpha,25(OH)(2)D(3), the active form of vitamin D(3), has been reported to
      regulate the cell biology of skeletal muscle. However, there has been some
      controversy about the expression of the vitamin D receptor (VDR) and thus the
      potential role of vitamin D(3) in skeletal muscle. In this study, we isolated and
      sequenced the full-length Vdr and Cyp27b1 transcripts in C2C12 myoblasts and
      myotubes. Western blots and immunocytochemistry confirmed protein expression in
      both myoblasts and myotubes clearly demonstrating that C2C12 cells express VDR
      and CYP27B1. To determine the vitamin D(3) action, we found that C2C12 myoblasts
      treated with either 1alpha,25(OH)(2)D(3) or 25(OH)D(3) inhibited cell
      proliferation and this was associated with increased Vdr expression. The
      observation that treatment of C2C12 myoblasts with the inactive form of vitamin
      D(3), [25(OH)D(3)], inhibited proliferation suggested that CYP27B1 was
      functionally active. We used small interfering RNA to knock down Cyp27b1 in
      myoblasts, and cells were treated with 25(OH)D(3). The growth-suppressive effects
      of 25(OH)D(3) were abolished, suggesting that CYP27B1 in myoblasts is necessary
      for the ability of 25(OH)D(3) to affect cell proliferation. Finally, we analyzed
      expression of VDR and CYP27B1 in regenerating skeletal muscle in vivo. We found
      that expression of VDR and CYP27B1 increased significantly at day 7 of
      regeneration, and these results confirm the expression of Vdr and Cyp27b1 in vivo
      and suggest a potential role for vitamin D(3) in skeletal muscle regeneration
      following injury.

PMID- 22648954
TI  - A difficult detection can influence survival analysis.

PMID- 22648953
TI  - p120-Catenin prevents neutrophil transmigration independently of RhoA inhibition
      by impairing Src dependent VE-cadherin phosphorylation.
AB  - Leukocyte transendothelial migration (TEM) is regulated by several signaling
      pathways including Src family kinases (SFK) and the small RhoGTPases. Previous
      studies have shown that vascular endothelial-cadherin (VE-cad) forms a complex
      with beta-,gamma-, and p120-catenins and this complex disassociates to form a
      transient gap during leukocyte TEM. Additionally, p120-catenin (p120-1A)
      overexpression in human umbilical vein endothelial cells (HUVEC) stabilizes VE
      cad surface expression, prevents tyrosine phosphorylation of VE-cad, and inhibits
      leukocyte TEM. Based on reports showing that p120 overexpression in fibroblasts
      or epithelial cells inhibits RhoA and activates Rac and Cdc42 GTPases, and on
      other reports showing that RhoA activation in endothelial cells is necessary for
      leukocyte TEM, we reasoned that p120 overexpression inhibited TEM through
      inhibition of RhoA. To test this idea, we overexpressed a mutant p120 isoform,
      p120-4A, which does not interact with RhoA. p120-4A colocalized with VE-cad in
      HUVEC junctions and enhanced VE-cad surface expression, similar to overexpression
      of p120-1A. Interestingly, overexpression of either p120-4A or p120-1A
      dramatically blocked TEM, and overexpression of p120-1A in HUVEC did not affect
      RhoA basal activity or activation of RhoA and Rac induced by thrombin or ICAM-1
      crosslinking. In contrast, biochemical studies revealed that overexpression of
      p120-1A reduced activated pY416-Src association with VE-cad. In summary, p120
      overexpression inhibits neutrophil TEM independently of an effect on RhoA or Rac
      and instead blocks TEM by preventing VE-cad tyrosine phosphorylation and
      association of active Src with the VE-cad complex.

PMID- 22648955
TI  - Fetal growth: a review of terms, concepts and issues relevant to obstetrics.
AB  - The perinatal literature includes several potentially confusing and controversial
      terms and concepts related to fetal size and growth. This article discusses fetal
      growth from an obstetric perspective and addresses various issues including the
      physiologic mechanisms that determine fetal growth trajectories, known risk
      factors for abnormal fetal growth, diagnostic and prognostic issues related to
      restricted and excessive growth and temporal trends in fetal growth. Also
      addressed are distinctions between fetal growth 'standards' and fetal growth
      'references', and between fetal growth charts based on estimated fetal weight vs
      those based on birth weight. Other concepts discussed include the incidence of
      fetal growth restriction in pregnancy (does the frequency of fetal growth
      restriction increase or decrease with increasing gestation?), the obstetric
      implications of studies showing associations between fetal growth and adult
      chronic illnesses (such as coronary heart disease) and the need for customizing
      fetal growth standards.

PMID- 22648956
TI  - Should LSIL-H be a distinct cytology category?: A study on the frequency and
      distribution of 40 human papillomavirus genotypes in 808 women.
AB  - BACKGROUND: The 2001 Bethesda System for gynecologic cervical cytology reporting
      classifies squamous intraepithelial lesions into low-grade (LSIL) and high-grade
      (HSIL) lesions. An intermediate term, "low-grade squamous intraepithelial lesion,
      cannot exclude high-grade squamous intraepithelial lesion (LSIL-H)," has been
      used in a small percentage of LSIL cases. To the authors' knowledge, little is
      known regarding the human papillomavirus (HPV) status in patients with LSIL-H.
      METHODS: A total of 808 SurePath specimens obtained between December 2009 and
      April 2011 were tested for 40 HPV genotypes using DNA microarray, followed by a
      confirmatory DNA sequencing assay. RESULTS: The infection rate for high-risk HPV
      in women with LSIL-H (92%) was strikingly close to that for women with HSIL
      (91%), which was higher than that for those with LSIL (74%); atypical squamous
      cells, cannot rule out high-grade lesion (ASC-H) (78%); or LSIL and ASC-H
      combined (74%). HPV type 16, the most common carcinogenic HPV genotype, was
      detected in 36% of women with LSIL-H, which was significantly higher than that in
      women with LSIL and ASC-H combined (13.8%), but less than that in women with HSIL
      (44.6%). Patients with LSIL-H and HSIL had similar infection rates for low
      risk/intermediate-risk HPV genotypes, which were lower than those in LSIL or LSIL
      and ASC-H combined. CONCLUSIONS: Women found to have LSIL-H on a Papanicolaou
      test appear to have a unique HPV distribution pattern that clearly differs from
      LSIL and is comparable to that for HSIL, suggesting an increased risk of high
      grade lesions over that of women with LSIL. Recognizing LSIL-H as an independent
      diagnostic category may help in the early identification of the high-risk
      subgroup that may require a management algorithm comparable to that for patients
      with HSIL. Cancer (Cancer Cytopathol) 2012. (c) 2012 American Cancer Society.

PMID- 22648957
TI  - Oxytocin enhances pupil dilation and sensitivity to 'hidden' emotional
      expressions.
AB  - Sensing others' emotions through subtle facial expressions is a highly important
      social skill. We investigated the effects of intranasal oxytocin treatment on the
      evaluation of explicit and 'hidden' emotional expressions and related the results
      to individual differences in sensitivity to others' subtle expressions of anger
      and happiness. Forty healthy volunteers participated in this double-blind,
      placebo-controlled crossover study, which shows that a single dose of intranasal
      oxytocin (40 IU) enhanced or 'sharpened' evaluative processing of others'
      positive and negative facial expression for both explicit and hidden emotional
      information. Our results point to mechanisms that could underpin oxytocin's
      prosocial effects in humans. Importantly, individual differences in baseline
      emotional sensitivity predicted oxytocin's effects on the ability to sense
      differences between faces with hidden emotional information. Participants with
      low emotional sensitivity showed greater oxytocin-induced improvement. These
      participants also showed larger task-related pupil dilation, suggesting that they
      also allocated the most attentional resources to the task. Overall, oxytocin
      treatment enhanced stimulus-induced pupil dilation, consistent with oxytocin
      enhancement of attention towards socially relevant stimuli. Since pupil dilation
      can be associated with increased attractiveness and approach behaviour, this
      effect could also represent a mechanism by which oxytocin increases human
      affiliation. 

PMID- 22648959
TI  - Poly(ethylene carbonate) nanoparticles as carrier system for chemotherapy showing
      prolonged in vivo circulation and anti-tumor efficacy.
AB  - The aim of this study is to investigate the feasibility and efficacy of PEC
      nanoparticles as delivery system for cancer chemotherapy. Assembly of paclitaxel
      loaded nanoparticles with high loading efficiency and narrow-size distribution is
      successful. For non-invasive in vivo tracing, nanoparticle blends of chelator
      bearing poly(lactide) with PEC and PLGA are successfully prepared.
      Pharmacokinetic studies in mice reveal a twofold higher circulation time of PEC
      as compared to PLGA. A tumor model shows an accumulation of PEC NPs in cancerous
      tissue and a higher anti-tumor efficiency compared to the standard TaxolTM, which
      is reflected in a significantly slower tumor growth compared to the NaCl control
      group.

PMID- 22648958
TI  - Event-related delta, theta, alpha and gamma correlates to auditory oddball
      processing during Vipassana meditation.
AB  - Long-term Vipassana meditators sat in meditation vs. a control (instructed mind
      wandering) states for 25 min, electroencephalography (EEG) was recorded and
      condition order counterbalanced. For the last 4 min, a three-stimulus auditory
      oddball series was presented during both meditation and control periods through
      headphones and no task imposed. Time-frequency analysis demonstrated that
      meditation relative to the control condition evinced decreased evoked delta (2-4
      Hz) power to distracter stimuli concomitantly with a greater event-related
      reduction of late (500-900 ms) alpha-1 (8-10 Hz) activity, which indexed altered
      dynamics of attentional engagement to distracters. Additionally, standard stimuli
      were associated with increased early event-related alpha phase synchrony (inter
      trial coherence) and evoked theta (4-8 Hz) phase synchrony, suggesting enhanced
      processing of the habituated standard background stimuli. Finally, during
      meditation, there was a greater differential early-evoked gamma power to the
      different stimulus classes. Correlation analysis indicated that this effect
      stemmed from a meditation state-related increase in early distracter-evoked gamma
      power and phase synchrony specific to longer-term expert practitioners. The
      findings suggest that Vipassana meditation evokes a brain state of enhanced
      perceptual clarity and decreased automated reactivity.

PMID- 22648960
TI  - Significance of palliative gastrectomy for late-stage gastric cancer patients.
AB  - PURPOSE: To investigate the significance of palliative gastrectomy for different
      types of metastatic gastric cancer patients displaying peritoneal dissemination,
      hepatic metastasis, distant lymph node metastasis occurring locally during late
      stage disease, and multi-organ metastases. METHODS: We performed a retrospective
      study of 862 patients who were histologically diagnosed as late-stage gastric
      cancer who could not undergo radical surgery at the Sun Yat-sen University Cancer
      Center between January 1993 and December 2008. The follow-up lasted until
      December 2010. Chi-square tests and Kaplan-Meier methods were employed to compare
      the adverse events and prognoses. RESULTS: In the peritoneal dissemination and
      multi-organ metastases groups, palliative gastrectomy has no survival benefit (P
      = 0.705, 0.331, respectively). In the patients with distant lymph-node
      metastases, liver metastasis and locally late-stage gastric cancer patients,
      palliative gastrectomy was a prognostic factor (P < 0.001, P < 0.001, P = 0.010,
      respectively). Multivariable analysis demonstrated that palliative gastrectomy
      was an independent prognostic factor for distant lymph-node metastases, liver
      metastasis, and local late-stage gastric cancer patients. Palliative gastrectomy
      combined with hepatectomy proved to be an independent prognostic factor to
      improve the overall survival of patients with liver metastases who underwent
      palliative gastrectomy (P = 0.008). CONCLUSION: For late-stage gastric cancer
      patients, palliative gastrectomy should be considered for locally late-stage,
      distant lymph node metastasis, and resectable liver metastasis patients.
      Especially among patients with liver metastasis, transfer medicine is essential
      for potentially curable patients to obtain access to radical surgery to improve
      the prognosis.

PMID- 22648961
TI  - From policy to reality: clinical managers' views of the organizational challenges
      of primary care reform in Portugal.
AB  - The primary healthcare reform in Portugal is based on the development of a new
      management model and clinical governance framework. The objective is to
      strengthen primary healthcare services to reduce the inappropriate utilization of
      secondary and emergency services and to make efficiency gains and to better
      control costs. New interventions include the introduction of a system of
      production-based incentives for family health units. This paper presents an
      initial assessment of the implementation of the new policies and tries to explain
      the gap between its expected results and what was observed in the field 5 years
      later. We used a Strengths, Weaknesses, Opportunities, and Threats analysis
      conducted in 12 regions, to collect the perceptions of members of Clinical
      Councils of Health Centers Groups, responsible for the implementation of the
      reform. The analysis looked at the dimensions of coverage, productivity,
      technical quality, and service quality. It identifies weaknesses in human
      resources management (shortages, incentives, team management) and lack of support
      from central and regional management. There is a perceived gap between the
      framework for reform as defined by law and the support made available for its
      implementation, leading to tensions between decision makers, managers, and health
      professionals.

PMID- 22648962
TI  - Clam's shell inspired high-energy inorganic coatings with underwater low adhesive
      superoleophobicity.
AB  - Unique underwater low adhesive superoleophobicity is discovered on the pallium
      covered region of a short clam's shell. This property originates from the shell's
      inorganic composition of CaCO(3)  and surface micro/nano-hierarchical structures.
      The oil-repellent shell provides an innovative strategy to develop novel
      underwater superoleophobic coatings using inorganic oxides such as copper oxide.
      This kind of coating is anticipated to be applied on engineering metals to
      protect aquatic equipment from oil contamination.

PMID- 22648963
TI  - Relapsed hepatoblastoma.
AB  - Successful treatment of recurrent hepatoblastoma (HB) relies largely on surgical
      resection. When tumors are responsive, chemotherapy can be used to render
      patients resectable. Various chemotherapeutic regimens studied in small numbers
      of patients on phase I/II trials have shown few responses. The best available
      data indicate that doxorubicin, if not given during intial treatment, and
      irinotecan are the most active agents in recurrent HB. Stem cell transplantation
      and radiation therapy have been reported in several patients with unclear
      successes. Advances in therapy for relapsed patients require concentrating
      enrollment in one or two phase I/II trials utilizing agents with promising
      preclinical data.

PMID- 22648964
TI  - Review of tandem repeat search tools: a systematic approach to evaluating
      algorithmic performance.
AB  - The prevalence of tandem repeats in eukaryotic genomes and their association with
      a number of genetic diseases has raised considerable interest in locating these
      repeats. Over the last 10-15 years, numerous tools have been developed for
      searching tandem repeats, but differences in the search algorithms adopted and
      difficulties with parameter settings have confounded many users resulting in
      widely varying results. In this review, we have systematically separated the
      algorithmic aspect of the search tools from the influence of the parameter
      settings. We hope that this will give a better understanding of how the tools
      differ in algorithmic performance, their inherent constraints and how one should
      approach in evaluating and selecting them.

PMID- 22648965
TI  - Scoring system for predicting recurrences in patients with papillary thyroid
      microcarcinoma.
AB  - CONTEXT: Papillary thyroid microcarcinomas (PMC) defined as tumors <=10 mm in
      diameter (including pT1a and pT3 according to the latest pTNM classification)
      have good prognosis, although recurrence is possible. Clinicians are interested
      in using a scoring system for predicting recurrences. OBJECTIVE: To identify the
      prognostic factors for recurrence in patients with PMC and to develop a scoring
      system based on lymph node involvement, multifocality, and sex. To determine the
      impact of extrathyroidal invasion (ETI) and a threshold value for analyzing
      multifocality. METHODS: Single-center retrospective study of a cohort of 1669
      patients with PMC managed from 1960 to 2007. The Kaplan-Meier survival rate and
      prognostic factors of events were analyzed using log-rank tests and uni- and
      multivariate Cox model-based analyses. A scoring system was proposed. RESULTS:
      Sixty-eight recurrences were observed. Initial lymph node metastases (P=0.0001),
      multifocality (P=0.05), and male sex (P=0.01) were significantly associated with
      recurrence, although there was a period effect (after 1990). PMC size was not a
      significant variable. Our scoring system allows us to separate patients into
      three risk groups according to their recurrence-free probability. For PMC Nx
      patients, total foci size of multifocal tumors >20 mm was significantly
      associated with recurrence (P<0.0001). Radioiodine (RAI) ablation was associated
      with better outcome only in PMC with ETI. CONCLUSION: Our scoring system
      classifies recurrence risk. In PMC Nx patients, multifocality is important in
      planning therapeutic strategies. Recurrence probability of pT3 PMC appears lower
      if RAI ablation is performed.

PMID- 22648966
TI  - Amino acid properties may be useful in predicting clinical outcome in patients
      with Kir6.2 neonatal diabetes.
AB  - BACKGROUND: Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the
      beta-cell K(ATP) channel, are a common cause of neonatal diabetes. The diabetes
      may be permanent neonatal diabetes mellitus (PNDM) or transient neonatal diabetes
      mellitus (TNDM), and in ~ 20% of patients, neurological features are observed. A
      correlation between the position of the mutation in the protein and the clinical
      phenotype has previously been described; however, recently, this association has
      become less distinct with different mutations at the same residues now reported
      in patients with different diabetic and/or neurological phenotypes. METHODS: We
      identified from the literature, and our unpublished series, KCNJ11 mutations that
      affected residues harbouring various amino acid substitutions (AAS) causing
      differences in diabetic or neurological status. Using the Grantham amino acid
      scoring system, we investigated whether the difference in properties between the
      wild-type and the different AAS at the same residue could predict phenotypic
      severity. RESULTS: Pair-wise analysis demonstrated higher Grantham scores for
      mutations causing PNDM or diabetes with neurological features when compared with
      mutations affecting the same residue that causes TNDM (P=0.013) or diabetes
      without neurological features (P=0.016) respectively. In just five of the 25 pair
      wise analyses, a lower Grantham score was observed for the more severe phenotype.
      In each case, the wild-type residue was glycine, the simplest amino acid.
      CONCLUSION: This study demonstrates the importance of the specific AAS in
      determining phenotype and highlights the potential utility of the Grantham score
      for predicting phenotypic severity for novel KCNJ11 mutations affecting
      previously mutated residues.

PMID- 22648967
TI  - Orientation independent retardation imaging using quantitative polarized phase
      microscopy.
AB  - Simultaneous optical phase and retardation measurement of a birefringent specimen
      is demonstrated independently of a priori knowledge of the optic axis
      orientation. The two-dimensional retardation distribution in both magnitude and
      angle of the fast axis orientation is uniquely determined from transverse phase
      images recorded with a bright field transmission microscope using light polarized
      at a minimum of three different polarization orientations. This approach opens a
      new possibility for stain-free phase and orientation-independent retardation
      characterization of samples using only one polarizer without needing other
      additional optical elements traditionally used in polarimetric measurements.

PMID- 22648969
TI  - Synthesis and characterization of PEG-based drug-responsive biohybrid hydrogels.
AB  - Interactive materials being responsive to a biocompatible stimulus represent a
      promising approach for future therapeutic applications. In this study, we present
      a novel biohybrid material synthesized from biocompatible components being
      stimulus-responsive to the pharmaceutically approved small-molecule novobiocin.
      The hydrogel design is based on the gyrase B (GyrB) protein, which is covalently
      grafted to multi-arm polyethylene glycol (PEG) using a Michael-type addition
      reaction. Upon addition of the GyrB-dimerizing substance coumermycin, stable
      hydrogels form which can be dissolved in a dose-adjustable manner by the
      antibiotic novobiocin. The switchable properties of this PEG-based hydrogel are
      favorable for future applications in tissue engineering and as externally
      controlled drug depot.

PMID- 22648968
TI  - Risk of retinoblastoma is associated with a maternal polymorphism in
      dihydrofolatereductase (DHFR) and prenatal folic acid intake.
AB  - BACKGROUND: The incidence of unilateral retinoblastoma varies globally,
      suggesting possible environmental contributors to disease incidence. Maternal
      intake of naturally occurring folate from vegetables during pregnancy is
      associated inversely with the risk of retinoblastoma in offspring. METHODS: The
      authors used a case-control study design to examine the association between
      retinoblastoma risk and maternal variations in the folate-metabolizing genes
      methylenetetrahydrofolate reductase (MTHFR) (a cytosine-to-thymine substitution
      at nucleotide 677 [MTHFR677C->T]; reference single nucleotide polymorphism
      rs1801133) and dihydrofolate reductase (DHFR) (a 19-base-pair deletion of intron
      1a [DHFR19bpdel]; rs70991108). In central Mexico, 103 mothers of children with
      newly diagnosed unilateral retinoblastoma were enrolled in an institutional
      review board-approved study along with a control group of 97 mothers who had
      healthy children. Mothers were interviewed regarding perinatal characteristics,
      including use of prenatal vitamin supplements, and gave peripheral blood samples,
      which were used for polymerase chain reaction-based genotyping of rs1801133 and
      rs70991108. RESULTS: The risk of having a child with unilateral retinoblastoma
      was associated with maternal homozygosity for DHFR19bpdel (odds ratio, 3.78; 95%
      confidence interval, 1.89-7.55; P = .0002), even after controlling for the
      child's DHFR19bpdel genotype (odds ratio, 2.81; 95% confidence interval, 1.32
      5.99; P = .0073). In a subgroup of 167 mothers with data on prenatal intake of
      supplements containing folic acid (a synthetic form of folate), DHFR19bpdel
      associated risk was elevated significantly only among those who reported taking
      folic acid supplements. Maternal MTHFR genotype was unrelated to the risk of
      having a child with retinoblastoma. CONCLUSIONS: Maternal homozygosity for a
      polymorphism in the DHFR gene necessary for converting synthetic folic acid into
      biologic folate was associated with an increased risk for retinoblastoma.
      Prenatal ingestion of synthetic folic acid supplements may be associated with
      increased risk for early childhood carcinogenesis in a genetically susceptible
      subset of the population.

PMID- 22648970
TI  - A new 2-pyrone derivative, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one,
      suppresses stemness in glioma stem-like cells.
AB  - Glioma cells with stem cell properties, termed glioma stem-like cells (GSCs),
      have been linked to tumor formation, maintenance, and progression and are
      responsible for the failure of chemotherapy and radiotherapy. Because
      conventional glioma treatments often fail to eliminate GSCs completely, residual
      surviving GSCs are able to repopulate the tumor. Compounds that target GSCs might
      be helpful in overcoming resistance to anticancer treatments in human brain
      tumors. In this study, we showed that 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2
      one (BHP), a new 2-pyrone derivative, suppressed the maintenance of the GSC
      population in both a glioma cell line and patient-derived glioma cells. Treatment
      of GSCs with BHP effectively inhibited sphere formation and suppressed the
      CD133(+) cell population. Treatment with BHP also suppressed expression of the
      stemness-regulating transcription factors Sox2, Notch2, and beta-catenin in
      sphere-cultured glioma cells. Treatment of GSCs with BHP significantly suppressed
      two fundamental characteristics of cancer stem cells: self-renewal and
      tumorigenicity. BHP treatment dramatically inhibited clone-forming ability at the
      single-cell level and suppressed in vivo tumor formation. BHP markedly inhibited
      both phosphoinositide 3-kinase/Akt and Ras/Raf-1/extracellular signal-regulated
      kinase signaling, which suggests that one or both of these pathways are involved
      in BHP-induced suppression of GSCs. In addition, treatment with BHP effectively
      sensitized GSCs to chemotherapy and radiotherapy. Taken together, these results
      indicate that BHP targets GSCs and enhances their sensitivity to anticancer
      treatments and suggest that BHP treatment may be useful for treating brain tumors
      by eliminating GSCs.

PMID- 22648971
TI  - Neurosteroid analog photolabeling of a site in the third transmembrane domain of
      the beta3 subunit of the GABA(A) receptor.
AB  - Accumulated evidence suggests that neurosteroids modulate GABA(A) receptors
      through binding interactions with transmembrane domains. To identify these
      neurosteroid binding sites directly, a neurosteroid-analog photolabeling reagent,
      (3alpha,5beta)-6-azi-pregnanolone (6-AziP), was used to photolabel membranes from
      Sf9 cells expressing high-density, recombinant, His(8)-beta3 homomeric GABA(A)
      receptors. 6-AziP inhibited (35)S-labeled t-butylbicyclophosphorothionate binding
      to the His(8)-beta3 homomeric GABA(A) receptors in a concentration-dependent
      manner (IC(50) = 9 +/- 1 MUM), with a pattern consistent with a single class of
      neurosteroid binding sites. [(3)H]6-AziP photolabeled proteins of 30, 55, 110,
      and 150 kDa, in a concentration-dependent manner. The 55-, 110-, and 150-kDa
      proteins were identified as His(8)-beta3 subunits through immunoblotting and
      through enrichment on a nickel affinity column. Photolabeling of the beta3
      subunits was stereoselective, with [(3)H]6-AziP producing substantially greater
      labeling than an equal concentration of its diastereomer [(3)H](3beta,5beta)-6
      AziP. High-resolution mass spectrometric analysis of affinity-purified, 6-AziP
      labeled His(8)-beta3 subunits identified a single photolabeled peptide, ALLEYAF-6
      AziP, in the third transmembrane domain. The identity of this peptide and the
      site of incorporation on Phe301 were confirmed through high-resolution tandem
      mass spectrometry. No other sites of photoincorporation were observed despite 90%
      sequence coverage of the whole beta3 subunit protein, including 84% of the
      transmembrane domains. This study identifies a novel neurosteroid binding site
      and demonstrates the feasibility of identifying neurosteroid photolabeling sites
      by using mass spectrometry.

PMID- 22648973
TI  - Tetrahydrobiopterin protects soluble guanylate cyclase against oxidative
      inactivation.
AB  - Tetrahydrobiopterin (BH4) is a major endogenous vasoprotective agent that
      improves endothelial function by increasing nitric oxide (NO) synthesis and
      scavenging of superoxide and peroxynitrite. Therefore, administration of BH4 is
      considered a promising therapy for cardiovascular diseases associated with
      endothelial dysfunction and oxidative stress. Here we report on a novel function
      of BH4 that might contribute to the beneficial vascular effects of the pteridine.
      Treatment of cultured porcine aortic endothelial cells with nitroglycerin (GTN)
      or 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) resulted in heme oxidation
      of soluble guanylate cyclase (sGC), as evident from diminished NO-induced cGMP
      accumulation that was paralleled by increased cGMP response to a heme- and NO
      independent activator of soluble guanylate cyclase [4-([(4-carboxybutyl)[2-(5
      fluoro-2-([4'-(trifluoromethyl)biphenyl-4
      yl]methoxy)phenyl)ethyl]amino]methyl)benzoic acid (BAY 60-2770)]. Whereas
      scavenging of superoxide and/or peroxynitrite with superoxide dismutase, tiron,
      Mn(III)tetrakis(4-benzoic acid)porphyrin, and urate had no protective effects,
      supplementation of the cells with BH4, either by application of BH4 directly or
      of its precursors dihydrobiopterin or sepiapterin, completely prevented the
      inhibition of NO-induced cGMP accumulation by GTN and ODQ. Tetrahydroneopterin
      had the same effect, and virtually identical results were obtained with RFL-6
      fibroblasts, suggesting that our observation reflects a general feature of
      tetrahydropteridines that is unrelated to NO synthase function and not limited to
      endothelial cells. Protection of sGC against oxidative inactivation may
      contribute to the known beneficial effects of BH4 in cardiovascular disorders
      associated with oxidative stress.

PMID- 22648972
TI  - Carbonylation induces heterogeneity in cardiac ryanodine receptor function in
      diabetes mellitus.
AB  - Heart failure and arrhythmias occur at 3 to 5 times higher rates among
      individuals with diabetes mellitus, compared with age-matched, healthy
      individuals. Studies attribute these defects in part to alterations in the
      function of cardiac type 2 ryanodine receptors (RyR2s), the principal Ca(2+)
      release channels on the internal sarcoplasmic reticulum (SR). To date, mechanisms
      underlying RyR2 dysregulation in diabetes remain poorly defined. A rat model of
      type 1 diabetes, in combination with echocardiography, in vivo and ex vivo
      hemodynamic studies, confocal microscopy, Western blotting, mass spectrometry,
      site-directed mutagenesis, and [(3)H]ryanodine binding, lipid bilayer, and
      transfection assays, was used to determine whether post-translational
      modification by reactive carbonyl species (RCS) represented a contributing cause.
      After 8 weeks of diabetes, spontaneous Ca(2+) release in ventricular myocytes
      increased ~5-fold. Evoked Ca(2+) release from the SR was nonuniform
      (dyssynchronous). Total RyR2 protein levels remained unchanged, but the ability
      to bind the Ca(2+)-dependent ligand [(3)H]ryanodine was significantly reduced.
      Western blotting and mass spectrometry revealed RCS adducts on select basic
      residues. Mutation of residues to delineate the physiochemical impact of
      carbonylation yielded channels with enhanced or reduced cytoplasmic Ca(2+)
      responsiveness. The prototype RCS methylglyoxal increased and then decreased the
      RyR2 open probability. Methylglyoxal also increased spontaneous Ca(2+) release
      and induced Ca(2+) waves in healthy myocytes. Treatment of diabetic rats with RCS
      scavengers normalized spontaneous and evoked Ca(2+) release from the SR, reduced
      carbonylation of RyR2s, and increased binding of [(3)H]ryanodine to RyR2s. From
      these data, we conclude that post-translational modification by RCS contributes
      to the heterogeneity in RyR2 activity that is seen in experimental diabetes.

PMID- 22648974
TI  - Chronic rhinosinusitis and occupational risk factors among 20- to 75-year-old
      Danes-A GA(2) LEN-based study.
AB  - BACKGROUND: Very little is known about occupational risk factors for chronic
      rhinosinusitis (CRS). The aim of this study was to evaluate occupational and
      other potential risk factors for CRS in a Danish population. METHODS: A cross
      sectional survey study among 4,554 Danes aged 20-75 years evaluated self-reported
      symptoms of CRS, asthma, and nasal allergy, along with information on smoking
      habits and occupation. RESULTS: A total of 3,099 returned completed
      questionnaires (response rate 68.1%). The overall CRS prevalence was 7.8% with no
      significant differences related to age or gender. Risk ratio estimates revealed
      an increased risk of CRS among female blue collar workers compared to female
      white collar workers. Among men the effect of occupation depended on smoking
      status. Occupational exposure to gasses, fumes, dust, or smoke increased the
      overall risk of CRS. CRS was reported approximately four times as often in
      subjects with asthma and in subjects with nasal allergy. Current smoking doubled
      the CRS prevalence. CONCLUSIONS: CRS prevalence was affected by occupation (blue
      vs. white collar), but the observed effect depended on gender and smoking status.
      Exposure to airway irritants (occupational or smoking) increased the CRS
      prevalence. Studies on larger cohorts are needed to fully assess these
      tendencies, for example, by more extensive use of Job Exposure Matrix models.

PMID- 22648975
TI  - A systematic approach to exosome-based translational nanomedicine.
AB  - Exosomes are a type of cell-derived extracellular nanovesicle. They relay
      information between cells. Some known exosome functions include immune
      modulation, promotion of angiogenesis, and tumor metastasis. To date, clinical
      use of exosomes has focused predominantly on evaluating their efficacy as cancer
      vaccines or diagnostically as biomarker containers. However, few investigations
      have explored their potential to serve as a platform for the development of semi
      synthetic nanovesicles. Given their nanoscale size, potential to express
      targeting ligands in native conformations and deformable structure, exosomes
      offer a logical biological vesicle platform for adapting and producing semi
      synthetic vesicles with excellent potential for nanomedicine applications.
      However, there are obstacles associated with realizing this potential that must
      be addressed. Thus, a systematic approach to isolating, modifying, and testing
      exosomes is presented to facilitate the introduction of exosome-based
      translational nanomedicine.

PMID- 22648977
TI  - Summary outcomes of two-stage resection for advanced colorectal liver metastases.
AB  - BACKGROUND: Surgical resection is associated with improved long-term survival in
      patients with colorectal liver metastases (CLM). However, majority of patients
      have unresectable bilobar advanced liver metastases. Two-stage resection (TSR)
      allows selected patients to achieve complete resection when combined with
      chemotherapy and interventional radiological procedures. METHODS: Electronic
      search of the MEDLINE and PubMed databases (January 2000-October 2011) to
      identify studies examining the outcomes of the surgical approach of TSR of
      advanced CLM was undertaken. RESULTS: Twelve studies were examined. This
      comprised 488 patients. A median of 77% (range: 64-100%) of planned patients
      completed TSR. The most common reason for failure was due to disease progression
      observed in a median of 100% (range: 56-100%) of patients. Second-stage resection
      appeared to be more morbid compared to first-stage resection with higher
      complication rates (33% vs. 14%) and requiring more blood transfusions (3 U vs. 1
      U). Completed TSR achieved a median survival of 37 (range: 18-66) months, median
      3-year survival rate of 60% (range: 45-84%), and median 5-year survival rate of
      48% (range: 32-70%). In patients who failed TSR, the median survival was 16
      (range: 10-29) months. CONCLUSION: In carefully selected candidates with advanced
      bilobar CLM, the TSR approach achieves long-term survival in patients who would
      otherwise be considered for palliative chemotherapy only. Despite failing to
      complete TSR, patients had an encouraging survival outcome that appeared to
      compare favorably over palliative chemotherapy alone.

PMID- 22648976
TI  - Enzymatic mineralization of hydrogels for bone tissue engineering by
      incorporation of alkaline phosphatase.
AB  - Alkaline phosphatase (ALP), an enzyme involved in mineralization of bone, is
      incorporated into three hydrogel biomaterials to induce their mineralization with
      calcium phosphate (CaP). These are collagen type I, a mussel-protein-inspired
      adhesive consisting of PEG substituted with catechol groups, cPEG, and the
      PEG/fumaric acid copolymer OPF. After incubation in Ca-GP solution, FTIR, EDS,
      SEM, XRD, SAED, ICP-OES, and von Kossa staining confirm CaP formation. The amount
      of mineral formed decreases in the order cPEG > collagen > OPF. The
      mineral:polymer ratio decreases in the order collagen > cPEG > OPF.
      Mineralization increases Young's modulus, most profoundly for cPEG. Such
      enzymatically mineralized hydrogel/CaP composites may find application as bone
      regeneration materials.

PMID- 22648978
TI  - Regulation of bone mass and osteoclast function depend on the F-actin modulator
      SWAP-70.
AB  - Bone remodeling involves tightly regulated bone-resorbing osteoclasts and bone
      forming osteoblasts. Determining osteoclast function is central to understanding
      bone diseases such as osteoporosis and osteopetrosis. Here, we report a novel
      function of the F-actin binding and regulatory protein SWAP-70 in osteoclast
      biology. F-actin ring formation, cell morphology, and bone resorption are
      impaired in Swap-70(-/-) osteoclasts, whereas the expression of osteoclast
      differentiation markers induced in vitro by macrophage colony-stimulating factor
      (M-CSF) and receptor activator of NF-kappaB ligand (RANKL) remains unaffected.
      Swap-70(-/-) mice develop osteopetrosis with increased bone mass, abnormally
      dense bone, and impaired osteoclast function. Ectopic expression of SWAP-70 in
      Swap-70(-/-) osteoclasts in vitro rescues their deficiencies in bone resorption
      and F-actin ring formation. Rescue requires a functional pleckstrin homology (PH)
      domain, known to support membrane localization of SWAP-70, and the F-actin
      binding domain. Transplantation of SWAP-70-proficient bone marrow into Swap-70(-/
      ) mice restores osteoclast resorption capacity in vivo. The identification of the
      role of SWAP-70 in promoting osteoclast function through modulating membrane
      proximal F-actin rearrangements reveals a new pathway to control osteoclasts and
      bone homeostasis.

PMID- 22648979
TI  - Chemotherapeutic approaches for newly diagnosed hepatoblastoma: past, present,
      and future strategies.
AB  - Surgical resection is the foundation of therapy in hepatoblastoma (HB), yet most
      patients have unresectable tumors at diagnosis. Patients with resectable tumors
      have event-free survival (EFS) of 80-90% and can be cured with cisplatin, 5
      fluorouracil, and vincristine. Patients whose tumors are unresectable but without
      overt metastases at diagnosis have EFS of 60-70%, and many can be rendered
      resectable without doxorubicin. Children with metastatic disease have fared
      poorly with 20-50% EFS, and new approaches for these patients remain desperately
      needed. Dose intensification of cisplatin and doxorubicin appears beneficial in
      high-risk patients. Future treatment strategies, which may be useful, include
      increasing intensity and/or duration of therapy, developing a maintenance regimen
      (oral irinotecan), using liver transplantation more often for patients to undergo
      complete resection, and identifying and incorporating novel agents. A better
      understanding of the biologic and pathologic factors is critical for predicting
      tumor behavior and developing more logical risk-based treatments.

PMID- 22648980
TI  - Improving the ordering and photovoltaic properties by extending pi-conjugated
      area of electron-donating units in polymers with D-A structure.
AB  - A systematic molecular design process from PBDTTT-S to PBDTDTTT-S-T, a high
      performance semiconducting polymer for organic photovoltaics, has been achieved
      by enhancing structural order, self-assembly and carrier mobility. Solar cells
      made from PBDTDTTT-S-T blended with PC(70) BM show a power conversion efficiency
      (PCE) of 7.81%, which is 25% higher than that of the parent PBDTTT-S.

PMID- 22648981
TI  - Effect of processing methods for transmission electron microscopy on corneal
      collagen fibrils diameter and spacing.
AB  - INTRODUCTION: The corneal tissue was processed in fixatives and embedded in resin
      for transmission electron microscopy to observe the ultrastructure of the
      collagen fibrils (CFs). The effect of these processing methods on the CF diameter
      and the interfibrillar spacing was studied. METHODS: Four normal human corneal
      buttons were used for this study. A part of each cornea was fixed in 2.5%
      glutaraldehyde containing cuprolinic blue in sodium acetate buffer and embedded
      in spurr's resin (SpurrCB). A second part of each cornea was fixed in 2.5%
      glutaraldehyde + osmium tetroxide and embedded spurr's resin (SpurrOsm). The
      third part of each cornea was fixed in paraformaldehyde (4%) and embedded in LR
      White at 4 degrees C (LRWhite). Ultrathin sections were stained with uranyl
      acetate and lead citrate. RESULTS: In the tissue, fixed in SpurrCB, the diameter
      was 38.4 +/- 5.9 nm and spacing between CF was 52.5 +/- 5.3 nm. In the tissue
      fixed in SpurrOsm, the diameter was 28.37 +/- 5.84 nm and spacing between CF was
      45 +/- 4.57 nm. In the tissue fixed in LR White, the CF diameter was 24 +/- 2.3
      nm and spacing between CF was 39.0 +/- 4.2 nm. The diameters and interfibrillar
      spacing of the tissue processed by SpurrCB, SpurrOsm, and LRWhite were
      significantly different (P < 0.001) from one another. CONCLUSION: Our study shows
      that there is a variation in the CF diameter and spacing depending on the method
      of fixation and embedding resins used. This needs to be considered when
      comparative studies using different methods are done.

PMID- 22648982
TI  - Listen, understand, engage.

PMID- 22648984
TI  - Middle meatal spacers for the prevention of synechiae following endoscopic sinus
      surgery: a systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Middle meatal (MM) synechiae is the most common complication
      following endoscopic sinus surgery (ESS) for chronic rhinosinusitis. To prevent
      synechiae formation, a variety of MM spacers have been employed, with varying
      success in the reported literature. There remains a continued debate on whether
      MM spacers actually reduce the risk of synechiae following ESS. METHODS: The
      Preferred Reporting of Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines was used for reporting this review of randomized controlled trials
      evaluating the effectiveness of MM spacers compared to no spacers in patients
      undergoing ESS. Where appropriate, a meta-analysis on outcome data using a random
      effects model was performed. RESULTS: Eight randomized controlled trials were
      included in this systematic review. A pooled analysis on relevant trials found a
      nonsignificant trend favoring MM spacers compared to no spacers for the
      prevention of synechiae following ESS (relative risk [RR], 0.40; 95% confidence
      interval [CI], 0.14-1.12). Subgroup analysis suggested that nonabsorbable spacers
      (NAS) may be more effective than absorbable spacers (AS) for reducing the risk of
      synechiae compared to no spacers. CONCLUSION: MM spacers may be more effective
      than no spacers for the prevention of synechiae following ESS, especially when
      employing the use of an NAS. However, significant heterogeneity is observed among
      included trials and future studies are needed to further validate these findings.

PMID- 22648985
TI  - Poly(2-ethyl-2-oxazoline) as alternative for the stealth polymer poly(ethylene
      glycol): comparison of in vitro cytotoxicity and hemocompatibility.
AB  - Limitations of PEG in drug delivery have been reported from clinical trials.
      PEtOx (0.4-40 kDa) as alternative is synthesized by a living, microwave-assisted
      polymerization, and is directly compared to PEG of similar molar mass regarding
      cytotoxicity and hemocompatibility. In short-term treatments, both types of
      polymers are well tolerated even at high concentrations. Moderate concentration
      and molar mass dependent cytotoxic effects occurred only after long-term
      incubation at concentrations higher than therapeutic doses. PEtOx possesses not
      only an easy route of synthesis and beneficial physicochemical characteristics
      such as low viscosity and high stability, which are advantageous over PEG, but
      additionally in vitro toxicology comparable to PEG.

PMID- 22648983
TI  - Long-chain polyacetals from plant oils.
AB  - Plant oil-derived alpha,omega-diacetals are polycondensated to the novel
      polyacetals [OCH(2) O(CH(2))(y)](n) (y = 19 and 23) with molecular weight of ca.
      M(n) = 2 * 10(4) g mol(-1). The long methylene sequences provide substantial melt
      and crystallization temperatures (T(m) = 88  degrees C and T(c) = 68  degrees C
      for y = 23), and rates of hydrolytic degradation are dramatically lower for the
      long-chain polyacetals versus a shorter chain analogue (y = 12) studied for
      comparison.

PMID- 22648986
TI  - Risk factors and musculoskeletal disorders among women workers performing fish
      processing.
AB  - BACKGROUND: The study examined the prevalence of musculoskeletal pain and
      discomfort (MSD) among workers engaged in fish processing activities and
      identified the occupational, environmental, and psychosocial factors contributing
      to the MSDs. METHODS: An ergonomics checklist and questionnaire on general health
      and psycho-social issues were administered to women workers (N = 450). The
      relative risk for MSDs due to demographic factors, stress symptoms, and task
      variables were estimated. RESULTS: Nearly 71% of the women (age 23.0 +/- 6.4
      years) reported MSDs, chiefly in upper back (54%), lower back (33%), knee (35%),
      and shoulders (27%). Workers engaged in mixed task (OR 13.8; CI 8.7-22.0), ring
      cutting (OR 18.3; CI 11.8-24.7), having job experience <3 years (OR1.9; CI1.3
      2.9), being married (OR 1.5; CI 1.1-2.2), BMI18-25 (OR 1.7; CI 1.1-2.8) had
      increased risk of MSDs in the upper back. The severity of pain was high among the
      workers with elevated co-morbidity (pain in two or more regions). One third of
      the workers perceived the work environment to be cause of their MSDs.
      Multivariate analysis using binary logistic regression model indicated that
      highly specialized job (OR 13.0; CI 4.7-14.2), high physical activity (OR 11.7;
      CI 4.6-12.7), improperly designed tools (OR 8.1; CI 3.5-9.5), poor training (OR
      7.0; CI 3.3-7.5), and poor job satisfaction (OR 1.5; CI 1.1-4.8) significantly
      increased the risk of MSDs. Almost all the psychosocial and work stress factors
      were associated with lower back MSD. CONCLUSION: A cold and humid environment,
      awkward standing work posture for long hours, high physical activities, poor task
      clarity, and high mental overload are important risk factors for the development
      of MSDs.

PMID- 22648987
TI  - Neoadjuvant chemotherapy (NACT) is an effective way of managing elderly women
      with advanced stage ovarian cancer (FIGO Stage IIIC and IV).
AB  - BACKGROUND: To compare outcomes in women >= age 70 who receive neoadjuvant
      chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC) followed by
      cytoreductive surgery with those undergoing upfront cytoreductive surgery
      followed by the same chemotherapy. METHODS: A retrospective cohort study was
      performed for women >= age 70 with Stage IIIC or Stage IV EOC from 1996 to 2009.
      RESULTS: Sixty-two patients who underwent upfront cytoreductive surgery and 42
      patients who received NACT were eligible for analysis. Patients receiving NACT
      were significantly more likely to have Stage IV disease (P = 0.004).
      Cytoreduction to no macroscopic disease was achieved in 71.4% of women who
      received NACT and 28.1% of women undergoing upfront surgery (P < 0.001). NACT
      patients had significantly less blood loss at surgery (P = 0.01), required fewer
      small bowel resections (P = 0.009), had shorter ICU stays (P = 0.02) and fewer
      hospital days (P = 0.04). NACT patients experienced a trend toward an improved
      progression-free survival (P = 0.078); however, no statistically significant
      differences were found in either the progression-free or overall survival
      analyses. CONCLUSION: NACT is associated with reduced perioperative morbidity in
      elderly patients with advanced stage ovarian cancer.

PMID- 22648988
TI  - Microwave-assisted seeded growth of lanthanide-based nanoparticles for imaging
      and therapy.
AB  - Size control: Particles designed for imaging and therapy need to be size tunable
      to ensure their optimal performance. A highly reproducible procedure for the
      preparation of uniform, spherical, lanthanide-based nanoparticles (NPs) was
      developed. The size of the particles can be predefined to an accuracy of up to a
      few nanometers by microwave-generated temperature control and the choice of aging
      time (see figure).

PMID- 22648989
TI  - Optimization of staining conditions for microalgae with three lipophilic dyes to
      reduce precipitation and fluorescence variability.
AB  - When the fluorescence signal of a dye is being quantified, the staining protocol
      is an important factor in ensuring accuracy and reproducibility. Increasingly,
      lipophilic dyes are being used to quantify cellular lipids in microalgae.
      However, there is little discussion about the sensitivity of these dyes to
      staining conditions. To address this, microalgae were stained with either the
      lipophilic dyes often used for lipid quantification (Nile Red and BODIPY) or a
      lipophilic dye commonly used to stain neuronal cell membranes (DiO), and
      fluorescence was measured using flow cytometry. The concentration of the cells
      being stained was found not to affect the fluorescence. Conversely, the
      concentration of dye significantly affected the fluorescence intensity from
      either insufficient saturation of the cellular lipids or formation of dye
      precipitate. Precipitates of all three dyes were detected as events by flow
      cytometry and fluoresced at a similar intensity as the chlorophyll in the
      microalgae. Prevention of precipitate formation is, therefore, critical to ensure
      accurate fluorescence measurement with these dyes. It was also observed that the
      presence of organic solvents, such as acetone and dimethyl sulfoxide (DMSO), were
      not required to increase penetration of the dyes into cells and that the presence
      of these solvents resulted in increased cellular debris. Thus, staining
      conditions affected the fluorescence of all three lipophilic dyes, but Nile Red
      was found to have a stable fluorescence intensity that was unaffected by the
      broadest range of conditions and could be correlated to cellular lipid content.

PMID- 22648990
TI  - Change in hip bone mineral density and risk of subsequent fractures in older men.
AB  - Low bone mineral density (BMD) increases fracture risk; how changes in BMD
      influence fracture risk in older men is uncertain. BMD was assessed at two to
      three time points over 4.6 years using dual-energy X-ray absorptiometry (DXA) for
      4470 men aged >=65 years in the Osteoporotic Fractures in Men (MrOS) Study.
      Change in femoral neck BMD was estimated using mixed effects linear regression
      models. BMD change was categorized as "accelerated" (<=-0.034 g/cm(2) ),
      "expected" (between 0 and -0.034 g/cm(2) ), or "maintained" (>=0 g/cm(2) ).
      Fractures were adjudicated by central medical record review. Multivariate
      proportional hazards models estimated the risk of hip, nonspine/nonhip, and
      nonspine fracture over 4.5 years after the final BMD measure, during which time
      371 (8.3%) men experienced at least one nonspine fracture, including 78 (1.7%)
      hip fractures. Men with accelerated femoral neck BMD loss had an increased risk
      of nonspine (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.4-2.8);
      nonspine/nonhip (HR = 1.6; 95% CI 1.1-2.3); and hip fracture (HR = 6.3; 95% CI
      2.7-14.8) compared with men who maintained BMD over time. No difference in risk
      was seen for men with expected loss. Adjustment for the initial BMD measure did
      not alter the results. Adjustment for the final BMD measure attenuated the change
      in BMD-nonspine fracture and the change in BMD-nonspine/nonhip relationships such
      that they were no longer significant, whereas the change in the BMD-hip fracture
      relationship was attenuated (HR = 2.6; 95% CI 1.1-6.4). Total hip BMD change
      produced similar results. Accelerated decrease in BMD is a strong, independent
      risk factor for hip and other nonspine fractures in men.

PMID- 22648991
TI  - MRT letter: Human bloodstains on antique aboriginal weapons: a guiding low-vacuum
      SEM study of erythrocytes in experimental samples on ethnographically documented
      biological raw materials.
AB  - The aboriginal use of reed and bone as raw materials for knives and daggers,
      respectively, has been well-documented ethnographically in some geographical
      areas of Melanesia. Because of the significant role that these weapons played in
      inter- and intra-ethnic aggression, they can potentially have retained smears
      from the contact with human blood. To carry out a guiding low-vacuum scanning
      electron microscopy (SEM) study of specific interest to ethnography, the outsides
      of a fragment of stalk of giant cane (Arundo donax) and tibial diaphysis of
      domestic sheep (Ovis aries) were smeared with peripheral human blood. No
      biological specimen preparation was applied to the samples. After just over 1
      month, bloodstain boundaries and their neighboring inner areas were examined via
      secondary electrons by a variable-pressure SEM (VP-SEM) working in low-vacuum
      mode. On both substrates, bloodstains exhibited micro-scales. No janocyte
      (erythrocyte negative replica) was observed in the examined areas. However,
      erythrocytes were seen crowded together as grain-shaped corpuscles in the smear
      on reed, and several hecatocytes (moon-like shaped erythrocytes) were evidenced
      in the smear on bone. The results of this study suggest that a VP-SEM working in
      low-vacuum mode can be used fruitfully to detect blood remains in medium-sized
      reed and bone antique aboriginal artifacts. This procedure can prospectively help
      to ethnographic museum curators and aboriginal-art surveyors as an easy guiding
      test in the valuation of antique traditional weapons prior to acquisition, when
      the real use of a piece has been claimed by the supplier.

PMID- 22648993
TI  - RUNX3 is expressed in the epithelium of the gastrointestinal tract.

PMID- 22648992
TI  - Modulation by pregnenolone sulfate of filtering properties in the hippocampal
      trisynaptic circuit.
AB  - Short-term synaptic plasticity alters synaptic efficacy on a timescale that is
      relevant to encoding information in spike trains. The dynamics of this
      plasticity, combined with that of the feedback and feedforward contributions of
      local interneurons, impose frequency-dependent properties on neuronal networks
      with implications for nervous system function. The trisynaptic network of the
      hippocampus is especially well suited to selectively filter components of
      frequency-dependent signals that are transmitted from the entorhinal cortex. We
      measured presynaptic [Ca(2+)](i) in perforant path, mossy fiber, or Schaffer
      collateral terminals while simultaneously measuring field potentials of principal
      cells of the dentate, CA3, or CA1 synaptic fields over a range of stimulus
      frequencies of 2 to 77 Hz. In all three synaptic fields, the average [Ca(2+)](i)
      during a 500 ms stimulus train rose monotonically with stimulus frequency. The
      average population spike amplitude during this stimulus train, however, exhibited
      a non-linear relationship to frequency that was distinct for each of the three
      synaptic fields. The dentate synaptic field exhibited the characteristics of a
      low pass filter, while both CA synaptic fields had bandpass filter
      characteristics with a gain that was greater than 1 in the passband frequencies.
      Importantly, alteration of the dynamic properties of this network could
      significantly impact information processing performed by the hippocampus.
      Pregnenolone sulfate (PregS), has frequency-dependent effects on paired- and
      multipulse plasticity in the dentate and CA1 synaptic fields of the hippocampal
      formation. We investigated the PregS-dependent modulation of the dynamic
      properties of transmission by the principal cells of the three hippocampal
      synaptic fields. Importantly, PregS is capable of altering the pattern separation
      capabilities that may underlie hippocampal information processing.

PMID- 22648994
TI  - Risk factors for development of chronic rhinosinusitis in patients with allergic
      rhinitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory
      condition of the sinonasal cavity. CRS may be preceded by other sinonasal
      inflammatory diseases including allergic rhinitis (AR). It is unclear what
      factors may predispose patients with AR to develop CRS. METHODS: We performed a
      retrospective review of all patients diagnosed with AR (and not CRS) that
      presented to an otolaryngology clinic at a tertiary care center as part of a
      multidisciplinary allergy evaluation between March 2004 and November 2011.
      Medical records were evaluated for clinicodemographic factors including age,
      gender, smoking history, asthma, gastroesophageal reflux disease (GERD), aspirin
      sensitivity, nasal polyposis, seasonal AR, perennial AR, categories of positive
      antigens on formal allergy testing, and the following sinonasal anatomic variants
      on computed tomography (CT): infraorbital (Haller) cells, concha bullosa, frontal
      intersinus cells, and anterior ethmoid frontal recess cells. Patients who did not
      develop CRS after at least 4 years of follow-up were grouped into the AR cohort.
      Patients who developed CRS after at least 6 months of follow-up were grouped into
      the AR-CRS cohort. RESULTS: We found a statistically significant association
      between the presence of infraorbital (Haller) cells (odds ratio [OR] = 6.27) and
      frontal intersinus cells (OR = 18.37) with development of CRS on both univariate
      and multivariate logistical regressions. CONCLUSION: Sinonasal anatomical
      variants, specifically infraorbital and frontal intersinus cells, are associated
      with development of CRS in patients with AR. The presence of these variants
      identifies patients who should be counseled on compliance with medical therapy
      for AR to potentially prevent progression to CRS.

PMID- 22648996
TI  - OMIP-011: Characterization of circulating endothelial cells (CECs) in peripheral
      blood.

PMID- 22648997
TI  - Cognitive research in zoo-housed chimpanzees: influence of personality and impact
      on welfare.
AB  - We monitored chimpanzee welfare during the introduction of on-exhibit cognitive
      research training and testing, as measured by behavior and interest in such
      training, and related individual variation to personality assessments. We
      observed 11 chimpanzees (six males; five females) over a 16-month period and
      compared their behavior across three conditions: (1) Baseline
      (nontraining/research situations) and (2) an on-going, off-exhibit program of
      Husbandry Training and (3) Research Pod Activities, on-exhibit, group training
      for cognitive testing. There was considerable individual variation in their
      interest levels during research sessions; females and those scoring higher for
      Openness were present more frequently (including those who actively participated
      and those who observed others participating), but interest did not vary in
      relation to rates of self-directed behaviors (SDBs), rank, or the level of social
      disruptions within the group (i.e. large-scale displays or fights). The frequency
      of SDBs was predicted by the Neuroticism personality factor, but did not differ
      across baseline and training contexts, indicating that these activities do not
      negatively impact welfare. We also explored vigilance as an indicator of social
      uncertainty, but social monitoring did not differ in relation to either social
      context or rank. Finally, we explored how the specific characteristics of the
      research context impacted on SDBs; namely, social context, reward contingency,
      and visual access to keepers. SDBs increased only when visual access to keepers
      was restricted, suggesting that visual contact reduced uncertainty in novel
      training contexts. Overall, the introduction of a cognitive research program did
      not compromise welfare, and the chimpanzees' repeated interest and willingness to
      participate suggests that the research was enriching.

PMID- 22648995
TI  - Liver resection for complicated hepatocellular carcinoma: challenges but
      opportunity for long-term survivals.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is often diagnosed late because of the
      lack of pathognomonic symptoms. This study evaluated outcomes following liver
      resection (LR) for patients with HCC presenting with large tumor size (over 10
      cm), adjacent organ invasion, or ruptured tumor, which we termed as complicated
      HCC (cHCC). MATERIALS AND METHODS: We retrospectively reviewed 660 HCC patients
      who underwent LR between January 2001 and July 2005. The patients were grouped
      into cHCC and non-cHCC according to the defined criteria. The clinicopathological
      features were analyzed and compared between the two groups. RESULTS: Patients in
      the cHCC group required longer operative times and resulted in greater
      intraoperative blood loss and more severe surgical complications. The cHCC group
      had a higher incidence of HCC recurrence after LR, and the HCC recurrence had a
      tendency to be associated with extrahepatic metastasis. The 5-year RFS (P <
      0.0001) and OS (P < 0.0001) of cHCC and non-cHCC patients were 18.5% and 28.9%
      versus 37.5% and 57.6%, respectively. CONCLUSIONS: LR for cHCC can be a great
      challenge for liver surgeons. However, with comparable operative mortality rates
      and acceptable survival times, surgical resection should always be considered
      performing in patients with cHCC, if clinically feasible.

PMID- 22648998
TI  - Click mechanochemistry: quantitative synthesis of "ready to use" chiral
      organocatalysts by efficient two-fold thiourea coupling to vicinal diamines.
AB  - Mechanochemical methods of neat grinding and liquid-assisted grinding have been
      applied to the synthesis of mono- and bis(thiourea)s by using the click coupling
      of aromatic and aliphatic diamines with aromatic isothiocyanates. The ability to
      modify the reaction conditions allowed the optimization of each reaction, leading
      to the quantitative formation of chiral bis(thiourea)s with known uses as
      organocatalysts or anion sensors. Quantitative reaction yields, combined with the
      fact that mechanochemical reaction conditions avoid the use of bulk solvents,
      enabled solution-based purification methods (such as chromatography or
      recrystallization) to be completely avoided. Importantly, by using selected model
      reactions, we also show that the described mechanochemical reaction procedures
      can be readily scaled up to at least the one-gram scale. In that way,
      mechanochemical synthesis provides a facile method to fully transform valuable
      enantiomerically pure reagents into useful products that can immediately be
      applied in their designed purpose. This was demonstrated by using some of the
      mechanochemically prepared reagents as organocatalysts in a model Morita-Baylis
      Hillman reaction and as cyanide ion sensors in organic solvents. The use of
      electronically and sterically hindered ortho-phenylenediamine revealed that
      mechanochemical reaction conditions can be readily optimized to form either the
      1:1 or the 1:2 click-coupling product, demonstrating that reaction stoichiometry
      can be more efficiently controlled under these conditions than in solution-based
      syntheses. In this way, it was shown that excellent stoichiometric control by
      mechanochemistry, previously established for mechanochemical syntheses of
      cocrystals and coordination polymers, can also be achieved in the context of
      covalent-bond formation.

PMID- 22648999
TI  - Impact of MMX(r) mesalamine on improvement and maintenance of health-related
      quality of life in patients with ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis (UC) substantially reduces patients' health
      related quality of life (HRQoL). The current study examined the burden of disease
      and the impact of daily multimatrix (MMX(r)) mesalamine treatment on HRQoL for
      patients with active or quiescent mild-to-moderate UC. METHODS: Data were from a
      two-phase, multicenter, open-label study with mild-to-moderate UC patients. In
      the acute phase, 132 patients with active disease received MMX mesalamine 2.4-4.8
      g/day QD for 8 weeks. In the maintenance phase, 207 patients with quiescent
      disease received MMX mesalamine 2.4 g/day QD for 12 months. The Short Form-12
      (version 2) (SF-12v2) measured HRQoL during each phase. Disease burden was
      examined by comparing acute-phase baseline scores with a U.S. general population
      sample. Repeated-measures analyses assessed change in SF-12v2 scores for each
      phase. Correspondence between HRQoL and disease activity was examined through
      correlations between SF-12v2 scores with patient-reported symptom measures.
      RESULTS: Baseline SF-12v2 scores for patients with UC were generally much lower
      than for the general population sample, indicating a broad disease burden. In the
      acute phase, significant improvement was observed for most SF-12v2 scores at week
      8; a comparison with the matched norms showed a complete elimination of burden.
      No changes in SF-12v2 scores were observed during the maintenance phase. Changes
      in symptom measures and SF-12v2 scores were moderately correlated. CONCLUSIONS:
      The sizeable burden of active mild-to-moderate UC on HRQoL was eliminated
      following 8 weeks' treatment with MMX mesalamine 2.4-4.8 g/day. HRQoL remained
      stable over 12 months of maintenance treatment in patients with quiescent UC.

PMID- 22649000
TI  - Significance of the "delayed hyperintense portal vein sign" in the hepatobiliary
      phase MRI obtained with Gd-EOB-DTPA.
AB  - PURPOSE: To determine the significance of the delayed hyperintense portal vein
      sign in Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: This retrospective study was approved by the Institutional Review Board
      and the requirement for informed patient consent was obtained. Six-hundred and
      seventy patients who underwent Gd-EOB-DTPA-enhanced MRI were included in the
      study. Two readers who were blinded to clinical records reviewed MR images in
      consensus. The delayed hyperintense portal vein sign was defined if the portal
      vein appeared more hyperintense than surrounding liver parenchyma on the 30
      minute delayed hepatobiliary phase. The frequency of the delayed hyperintense
      portal vein sign and the association between the sign and serum biochemical tests
      were assessed. Multivariate analysis was performed to identify which variables
      were associated with the sign. Optimal cutoff values of variables for reflecting
      the sign were obtained with ROC analysis. RESULTS: The delayed hyperintense
      portal vein sign was observed in 13.0%. In multivariate analysis, a direct
      bilirubin level was associated with the delayed hyperintense portal vein sign.
      Optimum cutoff value for reflecting the delayed hyperintense portal vein sign was
      2.18 mg/dL (sensitivity, 89%; specificity, 96%). CONCLUSION: The delayed
      hyperintense portal vein sign in Gd-EOB-DTPA-enhanced MRI can potentially be used
      to reflect hepatobiliary function.

PMID- 22649001
TI  - A colonic biomarker of Parkinson's disease?

PMID- 22649002
TI  - Tremor and dystonia associated with thalamic cyst: a rare manifestation.

PMID- 22649003
TI  - Commentary for "tremor and dystonia associated with thalamic cyst: a rare
      manifestation".

PMID- 22649004
TI  - Identification of PRRT2 as the causative gene of paroxysmal kinesigenic
      dyskinesia.

PMID- 22649005
TI  - Lewy pathology in gastric and duodenal biopsies in Parkinson's Disease.

PMID- 22649006
TI  - Increased medial orbitofrontal [18F]fluorodopa uptake in Parkinsonian impulse
      control disorders.
AB  - BACKGROUND: Impulse control disorders (ICDs) occur frequently in PD patients.
      METHODS: To investigate the possible involvement of the mesostriatal and
      mesolimbic monoaminergic function in ICDs associated with PD, we examined
      patients with (n = 10) and without (n = 10) ICDs using the brain [(18)
      F]fluorodopa PET. RESULTS: Patients with ICDs (e.g., pathological gambling,
      hypersexuality, and compulsive eating) showed up to 35% higher [(18) F]fluorodopa
      uptake in the medial orbitofrontal cortex, compared to control patients, but no
      differences in the striatum. The results remained significant also after
      excluding subjects with comorbid psychiatric disorders. CONCLUSIONS: Increased
      monoaminergic activity in the medial orbitofrontal cortex might be associated
      with increased sensitivity for ICDs under dopamine-replacement therapy in PD.

PMID- 22649007
TI  - Genetic polymorphisms in IL10RA and TNF modify the association between blood
      transfusion and risk of non-Hodgkin lymphoma.
AB  - We conducted a population-based case-control study in Connecticut women to test
      the hypothesis that genetic variations in Th1 and Th2 cytokine genes may modify
      the association between blood transfusion and risk of non-Hodgkin lymphoma (NHL).
      Compared with women without blood transfusion, women with a history of
      transfusion had an increased risk of NHL if they carried IL10RA (rs9610) GG
      genotype [odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.1-3.2] or TNF
      (rs1800629) AG/AA genotypes (OR = 1.6, 95% CI: 0.9-2.7). We also found women with
      a history of transfusion had a decreased risk of NHL if they carried IL10RA
      (rs9610) AG/AA genotypes (OR = 0.6, 95% CI: 0.4-0.9) or TNF (rs1800629) GG
      genotype (OR = 0.7, 95% CI: 0.5-1.0). A similar pattern was also observed for B
      cell lymphoma but not for T-cell lymphoma. Statistically significant interactions
      with blood transfusion were observed for IL10RA (rs9610) (P(forinteraction) =
      0.003) and TNF (rs1800629) (P(forinteraction) = 0.012) for NHL overall and IL10RA
      (rs9610) (P(forinteraction) = 0.001) and TNF (rs1800629) (P(forinteraction) =
      0.019) for B-cell lymphoma. The results suggest that genetic polymorphisms in TNF
      and IL10RA genes may modify the association between blood transfusion and NHL
      risk.

PMID- 22649009
TI  - Assessment of accuracy of identification of pathogenic yeasts in microbiology
      laboratories in the United kingdom.
AB  - Rapid, accurate identification of yeast isolates from clinical samples has always
      been important given their innately variable antifungal susceptibility profiles.
      Recently, this has become paramount with the proposed introduction of species
      specific interpretive breakpoints for MICs obtained in yeast antifungal
      susceptibility tests (M. A. Pfaller, D. Andes, D. J. Diekema, A. Espinel-Ingroff,
      D. Sheehan, and CLSI Subcommittee for Antifungal Susceptibility Testing, Drug
      Resist. Updat. 13:180-195, 2010). Here, we present the results of a 12-month
      evaluation of the accuracy of identifications that accompany yeast isolates
      submitted to the Mycology Reference Laboratory (United Kingdom) for either
      confirmation of identity or susceptibility testing. In total, 1,781 yeast
      isolates were analyzed, and the robustness of prior identifications obtained in
      microbiology laboratories throughout the United Kingdom was assessed using a
      combination of culture on chromogenic agar, morphology on cornmeal agar, and
      molecular identification by pyrosequencing. Over 40% of isolates (755) were
      submitted without any suggested identification. Of those isolates with a prior
      identification, 100 (9.7%) were incorrectly identified. Error rates ranged from
      5.2% (for organisms submitted for antifungal susceptibility testing) to 18.2%
      (for organisms requiring confirmation of identity) and varied in a strictly
      species-specific manner. At least 50% of identification errors would be likely to
      affect interpretation of MIC data, with a possible impact on patient management.
      In addition, 2.3% of submitted cultures were found to contain mixtures of at
      least two yeast species. The vast majority of mixtures had gone undetected in the
      referring laboratory and would have impacted the interpretation of antifungal
      susceptibility profiles and patient management. Some of the more common
      misidentifications are discussed according to the identification method employed,
      with suggestions for avoiding such misinterpretations.

PMID- 22649008
TI  - SPRY2 loss enhances ErbB trafficking and PI3K/AKT signalling to drive human and
      mouse prostate carcinogenesis.
AB  - Loss of SPRY2 and activation of receptor tyrosine kinases are common events in
      prostate cancer (PC). However, the molecular basis of their interaction and
      clinical impact remains to be fully examined. SPRY2 loss may functionally
      synergize with aberrant cellular signalling to drive PC and to promote treatment
      resistant disease. Here, we report evidence for a positive feedback regulation of
      the ErbB-PI3K/AKT cascade by SPRY2 loss in in vitro as well as pre-clinical in
      vivo models and clinical PC. Reduction in SPRY2 expression resulted in hyper
      activation of PI3K/AKT signalling to drive proliferation and invasion by enhanced
      internalization of EGFR/HER2 and their sustained signalling at the early endosome
      in a PTEN-dependent manner. This involved p38 MAPK activation by PI3K to
      facilitate clathrin-mediated ErbB receptor endocytosis. Finally, in vitro and in
      vivo inhibition of PI3K suppressed proliferation and invasion, supporting
      PI3K/AKT as a target for therapy particularly in patients with PTEN
      haploinsufficient-, low SPRY2- and ErbB-expressing tumours. In conclusion, SPRY2
      is an important tumour suppressor in PC since its loss drives the PI3K/AKT
      pathway via functional interaction with the ErbB system.

PMID- 22649012
TI  - Comparison of PapType to Digene Hybrid Capture 2, Roche linear array, and
      Amplicor for detection of high-risk human papillomavirus genotypes in women with
      previous abnormal pap smears.
AB  - PapType human papillomavirus (HPV) assay was compared to Hybrid Capture 2 (HC2),
      Amplicor (Amp), and Linear Array (LA) HPV tests in 894 women undergoing
      management for a high-grade Pap smear abnormality. The sensitivity in detection
      of underlying high-grade histological diagnosis by PapType was 90.3% and by HC2
      was 79.8%, while by Amp and LA it was 92.4% and 91.6%, respectively. The
      specificities were 52.5%, 55.3%, 49.4%, and 51.7% for PapType, HC2, Amp, and LA,
      respectively.

PMID- 22649011
TI  - Recovery of Gram-negative bacilli in stored endotracheal aspirates.
AB  - This study assessed the recovery rates of Gram-negative bacilli from stored
      endotracheal aspirates frozen with and without glycerol. Samples frozen with
      glycerol showed a significant difference in isolate recovery, 89.7% versus 69.2%
      (P = 0.02). This study demonstrates that it is possible to achieve high recovery
      rates of potentially pathogenic organisms from endotracheal aspirates when stored
      with glycerol, thus broadening the scope of active surveillance cultures for both
      clinical and research purposes.

PMID- 22649010
TI  - Imported Klebsiella pneumoniae carbapenemase-producing K. pneumoniae clones in a
      Greek hospital: impact of infection control measures for restraining their
      dissemination.
AB  - The recent emergence of carbapenemase-producing Enterobacteriaceae strains
      represents a major threat for hospitalized patients. We document the
      dissemination and control of carbapenemase-producing Klebsiella pneumoniae clones
      in a Greek hospital. During a 3-year study period (January 2009 to December
      2011), carbapenemase-producing K. pneumoniae strains were isolated from clinical
      samples from 73 individual patients. Phenotyping and molecular testing confirmed
      that 52 patients were infected with K. pneumoniae carbapenemase 2 (KPC-2)
      producers, 12 were infected with VIM-1 producers, and the remaining 9 were
      infected with isolates producing both KPC-2 and VIM-1 enzymes. Twenty-eight of
      these clinical cases were characterized as imported health care associated, and
      23 of these were attributed to KPC producers and 5 were attributed to KPC and VIM
      producers. The remaining 45 cases were deemed hospital acquired. In the second
      year of the study, intensified infection control intervention was implemented,
      followed by active surveillance and carrier isolation in the third year. The
      incidence of carbapenemase-producing K. pneumoniae patient cases decreased from
      0.52/1,000 patient days in 2009 to 0.32/1,000 patient days in 2010 (P = 0.075).
      Following these additional infection control measures, the incidence fell to
      0.21/1,000 patient days in 2011 and differed significantly from that in 2009 (P =
      0.0028). Despite the fact that the imported cases of carbapenemase-producing K.
      pneumoniae were equally distributed over this 3-year period, the incidence of
      hospital-acquired cases decreased from 0.36/1,000 patient days in 2009 to
      0.19/1,000 patient days in 2010 (P = 0.058) and to 0.1/1,000 patient days in 2011
      (P = 0.0012). Our findings suggest that rigorous infection control measures and
      active surveillance can effectively reduce the incidence of secondary
      transmission due to KPC-producing pathogens.

PMID- 22649013
TI  - Multiclonal origin of macrolide-resistant Mycoplasma pneumoniae isolates as
      determined by multilocus variable-number tandem-repeat analysis.
AB  - There was a high percentage of macrolide resistance in Mycoplasma pneumoniae
      clinical isolates in China. The genetic relatedness of macrolide-resistant M.
      pneunomiae strains was investigated using the multilocus variable-number tandem
      repeat assay (MLVA). Among 152 M. pneunomiae isolates, the 137 macrolide
      resistant strains were clustered into 15 MLVA types, indicating that the high
      macrolide resistance rate in M. pneumoniae is a result of the dissemination of
      the multiple resistant clones.

PMID- 22649015
TI  - Field evaluation of a simple fluorescence method for detection of viable
      Mycobacterium tuberculosis in sputum specimens during treatment follow-up.
AB  - Simple tuberculosis (TB) treatment monitoring tools are needed. We assessed the
      performance of fluorescein-diacetate (FDA) smear microscopy for detection of
      viable Mycobacterium tuberculosis in sputum specimens (n = 288) of TB cases under
      treatment compared to culture (17.4% culture positivity). FDA sensitivity was
      moderate (83.7% [95% confidence interval {CI}, 70.3 to 92.6]), and specificity
      was low (66.1% [59.5 to 72.2]). The good negative predictive value (94.8% [90.1
      to 97.8]) and negative likelihood ratio (0.2) suggest using this method to rule
      out treatment failure in settings without access to culture.

PMID- 22649014
TI  - Quantification of Mycobacterium avium subsp. paratuberculosis strains
      representing distinct genotypes and isolated from domestic and wildlife animal
      species by use of an automatic liquid culture system.
AB  - Quantification of 11 clinical strains of Mycobacterium avium subsp.
      paratuberculosis isolated from domestic (cattle, sheep, and goat) and wildlife
      (fallow deer, deer, wild boar, and bison) animal species in an automatic liquid
      culture system (Bactec MGIT 960) was accomplished. The strains were previously
      isolated and typed using IS1311 PCR followed by restriction endonuclease analysis
      (PCR-REA) into type C, S, or B. A strain-specific quantification curve was
      generated for each M. avium subsp. paratuberculosis strain by relating the time
      to detection in the liquid culture system to the estimated log(10) CFU in each
      inoculum. According to their growth curves, the tested M. avium subsp.
      paratuberculosis strains were classified into two distinct groups. The first
      group included the S-type strain isolated from goat and all the sheep strains
      with C, S, and B genotypes. A second group contained the C- and B-type strains
      isolated from cattle, goat, and wildlife animals with the exception of the fallow
      deer strain. The strains isolated from cattle or sheep showed similar strain
      specific standard curves irrespective of their genotype. In contrast, the strains
      isolated from goat or from wildlife animal species varied in their rates of
      growth in liquid culture. Universal-standard curves and algorithms for the
      quantification of each group of strains were generated. In addition, the liquid
      culture system was compared with a real-time quantitative PCR system for the
      quantification of the 11 M. avium subsp. paratuberculosis strains. Correlations
      between the estimated log(10) CFU and M. avium subsp. paratuberculosis DNA copy
      numbers were very high for all the tested strains (R >= 0.9).

PMID- 22649016
TI  - Hyphal and yeast forms of Histoplasma capsulatum growing within 5 days in an
      automated bacterial blood culture system.

PMID- 22649017
TI  - Detection of Babesia hongkongensis sp. nov. in a free-roaming Felis catus cat in
      Hong Kong.
AB  - Intraerythrocytic Babesia-like trophozoites were seen in postmortem kidney
      sections of a free-roaming cat in Hong Kong. DNA sequences of the 18S rRNA and
      mitochondrial cytochrome b genes had only 96.7% and 90.4% nucleotide identity
      with known Babesia sequences. We propose that this new species be named Babesia
      hongkongensis.

PMID- 22649018
TI  - Diagnostic value of conjunctival swab sampling associated with nested PCR for
      different categories of dogs naturally exposed to Leishmania infantum infection.
AB  - The objective of the present study was to evaluate the diagnostic performance of
      a noninvasive assay, conjunctival swab (CS) nested-PCR (n-PCR), for diagnosing
      canine leishmaniasis (CanL) in different stages of infection in comparison to the
      performance of the indirect immunofluorescence antibody test (IFAT), lymph node
      microscopy, and buffy coat n-PCR. To this end, we performed a cross-sectional
      survey among 253 nonselected dogs in areas of endemicity in central Italy. We
      also performed a longitudinal study of CS n-PCR among 20 sick dogs undergoing
      antileishmanial treatment. In the first study, among the 72 animals that were
      positive by at least one test (28.45%), CS n-PCR showed the best relative
      performance (76.38%), with a high concordance in comparison to standard IFAT
      serology (kappa = 0.75). The highest positivity rates using CS n-PCR were found
      in asymptomatic infected dogs (84.2%) and sick dogs (77.8%); however, the
      sensitivity of the assay was not associated with the presence of clinical signs.
      In the follow-up study on treated sick dogs, CS n-PCR was the most sensitive
      assay, with promising prognostic value for relapses. The univariate analysis of
      risk factors for CanL based on CS n-PCR findings showed a significant correlation
      with age (P = 0.012), breed size (P = 0.026), habitat (P = 4.9 * 10(-4)), and
      previous therapy (P = 0.014). Overall, the results indicated that CS n-PCR was
      the most sensitive assay of the less invasive diagnostic methods and could
      represent a good option for the early and simple diagnosis of CanL infection in
      asymptomatic animals and for monitoring relapses in drug-treated dogs.

PMID- 22649019
TI  - Molecular characterization and second-line antituberculosis drug resistance
      patterns of multidrug-resistant Mycobacterium tuberculosis isolates from the
      northern region of South Africa.
AB  - Despite South Africa being one of the high-burden multidrug-resistant
      tuberculosis (MDR-TB) countries, information regarding the population structure
      of drug-resistant Mycobacterium tuberculosis strains is limited from many regions
      of South Africa. This study investigated the population structure and
      transmission patterns of drug-resistant M. tuberculosis isolates in a high-burden
      setting of South Africa as well as the possible association of genotypes with
      drug resistance and demographic characteristics. A total of 336 consecutive MDR
      TB isolates from four provinces of South Africa were genotyped using
      spoligotyping and mycobacterial interspersed repetitive-unit-variable number
      tandem repeat (MIRU-VNTR) typing. Drug susceptibility testing for ofloxacin,
      kanamycin, and capreomycin was performed using the agar proportion method. The
      results showed that 4.8% of MDR-TB isolates were resistant to ofloxacin, 2.7%
      were resistant to kanamycin, and 4.5% were resistant to capreomycin, while 7.1%
      were extensively drug resistant (XDR), and the remaining 83.6% were susceptible
      to all of the second-line drugs tested. Spoligotyping grouped 90.8% of the
      isolates into 25 clusters, while 9.2% isolates were unclustered. Ninety-one
      percent of the 336 isolates were assigned to 21 previously described shared
      types, with the Beijing family being the predominant genotype in the North-West
      and Limpopo Provinces, while the EAI1_SOM family was the predominant genotype in
      the Gauteng and Mpumalanga Provinces. No association was found between genotypes
      and specific drug resistance patterns or demographic information. The high level
      of diversity and the geographical distribution of the drug-resistant M.
      tuberculosis isolates in this study suggest that the transmission of TB in the
      study settings is not caused by the clonal spread of a specific M. tuberculosis
      strain.

PMID- 22649020
TI  - Detection of Wolbachia DNA in blood for diagnosing filaria-associated syndromes
      in cats.
AB  - A fundamental role for the endosymbiotic bacteria Wolbachia pipientis in the
      pathogenesis of Dirofilaria immitis infections has emerged in recent years.
      Diagnostic opportunities arising from this breakthrough have not yet been fully
      exploited. This study was aimed at developing conventional and real-time PCR
      assays to carry out a molecular survey in a convenience sample of cats living in
      an area where D. immitis is endemic and to evaluate the detection of bacterial
      DNA in blood as a surrogate assay for diagnosing filaria-associated syndromes in
      cats. COI and FtsZ loci were used as targets for D. immitis and Wolbachia PCR
      assays, respectively, and real-time TaqMan PCR assays were used only for
      Wolbachia. A convenience sample of 307 disease-affected or healthy cats examined
      at a University facility were PCR tested, and their medical records were
      investigated. Conventional nested PCR for Wolbachia amplified the endosymbionts
      of both D. immitis and D. repens, while real-time PCR was highly specific only
      for the former. Observed prevalences of 0.3 and 10.4% were found using
      conventional nested PCR assays for D. immitis and real-time PCR for Wolbachia,
      respectively. Similar prevalences were established using the Wolbachia nested PCR
      (98% concordance with real-time PCR). The group of Wolbachia-positive samples had
      a significantly higher proportion of subjects with respiratory signs (29.0%
      versus 9.7%; P = 0.002). The findings of this study indicate that a highly
      sensitive PCR assay can be used to detect the Wolbachia organism in the
      peripheral blood of cats with respiratory signs.

PMID- 22649021
TI  - Molecular typing and resistance analysis of travel-associated Salmonella enterica
      serotype Typhi.
AB  - Salmonella enterica serotype Typhi is a human pathogen causing 12 to 30%
      mortality and requiring antibiotic therapy to control the severity of the
      infection. Typhoid fever in United States is often associated with foreign travel
      to areas of endemicity. Increasing resistance to multiple drugs, including
      quinolones, is associated with decreased susceptibility to ciprofloxacin (DCS).
      We investigated 31 clinical strains isolated in Florida from 2007 to 2010,
      associated with travel to six countries, to examine the clonal distribution of
      the organism and apparent nalidixic acid (NAL) resistance. The strains were
      isolated from blood or stool of patients aged 2 to 68 years. The isolates were
      subtyped by ribotyping and pulsed-field gel electrophoresis. Susceptibilities to
      15 antimicrobials were determined, and the isolates were screened for integrons
      and gyrase A gene mutations. Both typing techniques effectively segregated the
      strains. Identical clones were associated with different countries, while diverse
      types coexisted in the same geographic location. Fifty-one percent of the strains
      were resistant to at least one antimicrobial, and five were resistant to three or
      more drugs (multidrug resistant [MDR]). All 12 isolates from the Indian
      subcontinent were resistant to at least one drug, and 83% of those were resistant
      to NAL. Three of the MDR strains harbored a 750-bp integron containing the dfr7
      gene. Ninety-three percent of the resistant strains showed a DCS profile. All the
      NAL-resistant strains contained point mutations in the quinolone resistance
      determining region of gyrA. This study affirms the global clonal distribution,
      concomitant genetic heterogeneity, and increased NAL resistance of S. enterica
      serovar Typhi.

PMID- 22649022
TI  - Molecular epidemiology of HIV-associated tuberculosis in Dar es Salaam, Tanzania:
      strain predominance, clustering, and polyclonal disease.
AB  - Molecular typing of Mycobacterium tuberculosis can be used to elucidate the
      epidemiology of tuberculosis, including the rates of clustering, the frequency of
      polyclonal disease, and the distribution of genotypic families. We performed
      IS6110 typing and spoligotyping on M. tuberculosis strains isolated from HIV
      infected subjects at baseline or during follow-up in the DarDar Trial in Tanzania
      and on selected community isolates. Clustering occurred in 203 (74%) of 275
      subjects: 124 (80%) of 155 HIV-infected subjects with baseline isolates, 56 (69%)
      of 81 HIV-infected subjects with endpoint isolates, and 23 (59%) of 39 community
      controls. Overall, 113 (41%) subjects had an isolate representing the East Indian
      "GD" family. The rate of clustering was similar among vaccine and placebo
      recipients and among subjects with or without cellular immune responses to
      mycobacterial antigens. Polyclonal disease was detected in 6 (43%) of 14 patients
      with multiple specimens typed. Most cases of HIV-associated tuberculosis among
      subjects from this study in Dar es Salaam resulted from recently acquired
      infection. Polyclonal infection was detected and isolates representing the East
      Indian GD strain family were the most common.

PMID- 22649023
TI  - Clinical outcome of central conventional chondrosarcoma.
AB  - INTRODUCTION: Aim of this study was to analyze (1) survival, local recurrence
      (LR), and metastasis rates between the three histological tumor grades; (2)
      whether type of treatment and tumor site influenced prognosis for each histologic
      grade. METHODS: We retrospectively studied 296 patients with central conventional
      chondrosarcomas (CS) (87 grade 1, 162 grade 2, and 47 grade 3). The femur was the
      most common site (91 cases), followed by the pelvis (82) and other less frequent
      sites. Type of surgery was related with histologic grade. Margins were wide in
      222 cases, marginal in 23, and intralesional in 51 cases. RESULTS: At a mean of 7
      years, 201 patients remained continuously NED, 33 were NED after treatment of
      relapse, 15 were AWD, 35 were died of disease, and 12 of other causes. Survival
      was 92% at 5 years and 84% at 10 years, significantly influenced by histological
      grading. In grade 3 CS, two factors influenced survival: type of surgery
      (resection vs. amputation, P = 0.051) and site (P = 0.039). The two significant
      factors lost their significance at multivariate analysis. CONCLUSION: Central
      conventional CS with low/intermediate grade has a good prognosis, while high
      grade tumors have poor outcome. Tumor relapses are strictly related with
      histologic grade.

PMID- 22649024
TI  - Efficacy and safety of oral and parenteral methotrexate therapy in children with
      juvenile idiopathic arthritis: an observational study with patients from the
      German Methotrexate Registry.
AB  - OBJECTIVE: The German Methotrexate Registry has been collecting data concerning
      the efficacy and safety of methotrexate (MTX) treatment since 2005. The aim of
      this retrospective analysis is to compare oral and parenteral MTX treatment
      regarding efficacy and safety. METHODS: Inclusion criteria were diagnosis of
      juvenile idiopathic arthritis, MTX treatment for at least 6 months, a consistent
      route of administration of MTX, and no previous or concomitant treatment with
      biologic agents. Efficacy was measured by the American College of Rheumatology
      (ACR) pediatric (Pedi) criteria. Primary outcome was efficacy defined as the
      number of patients reaching ACR Pedi 30 improvement criteria after 6 months of
      treatment. Secondary outcome criteria were the ACR Pedi 50 and Pedi 70 criteria
      at 6 and 12 months, respectively. Analyses were performed with the intent-to
      treat population. RESULTS: Of the 411 eligible patients, 259 (63%) received oral
      MTX and 152 (37%) received subcutaneous MTX. In both patient groups, a comparable
      weekly dose of MTX (0.4 mg/kg versus 0.42 mg/kg) was used, and a comparable
      number of patients received concomitant steroids. The primary outcome in both
      treatment groups was that a comparably high number of patients showed a clinical
      response according to the ACR Pedi 30 score after 6 months of treatment (73%
      versus 72%; P = 0.87). Twenty-two percent of patients with oral therapy and 27%
      with subcutaneous therapy had at least 1 documented adverse event.
      Discontinuation of treatment was observed in both groups with equal frequency,
      while significantly more patients with subcutaneous application discontinued MTX
      because of adverse events (11% versus 5%; P = 0.02). CONCLUSION: In this
      retrospective analysis, parenteral MTX was not superior to oral administration
      regarding efficacy and tolerability.

PMID- 22649025
TI  - Asymmetric supramolecular catalysis: a bio-inspired tool for the high asymmetric
      induction in the enamine-based Michael reactions.
AB  - King size: Utilization of large-size supramolecular rings in the pre-transition
      state (pre-TS) of enamine-based Michael reactions for high asymmetric induction
      is described. Enantiomerically pure, druglike hexahydroxanthenes with three
      contiguous stereocenters were synthesized through supramolecular catalysis by D
      proline and quinine-NH-thiourea followed by reductive etherification from simple
      precursors under mild conditions (see scheme).

PMID- 22649027
TI  - Neutralization of membrane TNF, but not soluble TNF, is crucial for the treatment
      of experimental colitis.
AB  - BACKGROUND: Agents neutralizing membrane tumor necrosis factor (mTNF) and soluble
      TNF (sTNF) are widely used for the treatment of inflammatory bowel disease (IBD).
      Neutralization of mTNF, however, is associated with increased susceptibility to
      infectious diseases. The aim of this study was to determine whether
      neutralization of sTNF exclusively, by the use of a dominant negative mutant of
      TNF (XENP1595), could reduce the severity of colitis in mice. METHODS: Colitis
      was induced in immunodeficient mice by transfer of CD45RB(hi) CD25 T-cells. Once
      the disease had developed, mice were treated twice a week with XENP1595,
      phosphate-buffered saline (PBS), anti-TNF monoclonal antibody (mAb), or isotype
      control. The anti-TNF mAb blocks both mTNF and sTNF. Weights, disease activity
      index, macroscopic inflammation of the colon, and histological sections were
      evaluated. T-cell populations from the colon were analyzed by flow cytometry.
      RESULTS: Treatment of mice with XENP1595 did not change the course of the
      disease, whereas mice treated with anti-TNF mAb recovered weight soon after the
      first treatment dose. Inflammation in the colon was reduced in mice treated with
      anti-TNF mAb compared to isotype control-treated animals. Mice treated with
      XENP1595 had a similar degree of inflammation in the colon as PBS-treated
      animals. The number of effector and regulatory T-cells in the colon remained
      unaffected by all treatments. CONCLUSIONS: Neutralization of sTNF exclusively was
      unable to induce remission in T-cell-mediated colitis, suggesting that
      neutralization of mTNF is crucial for the treatment of IBD.

PMID- 22649028
TI  - New look at renal vasculature: 7 tesla nonenhanced T1-weighted FLASH imaging.
AB  - PURPOSE: To investigate the feasibility of 7 Tesla (T) nonenhanced high field MR
      imaging of the renal vasculature and to evaluate the diagnostic potential of
      various nonenhanced T1-weighted (T1w) sequences. MATERIALS AND METHODS: Twelve
      healthy volunteers were examined on a 7T whole-body MR system (Magnetom 7T,
      Siemens Healthcare Sector) using a custom-built eight-channel radiofrequency (RF)
      transmit/receive body coil. Subsequent to RF shimming, the following sequences
      were acquired (i) fat-saturated two-dimensional (2D) FLASH, (ii) fat-saturated 3D
      FLASH, and a (iii) fat-saturated 2D time-of-flight MR angiography (TOF MRA). SNR
      and CNR were measured in the aorta and both renal arteries. Qualitative analysis
      was performed with regard to vessel delineation (5-point scale: 5 = excellent to
      1 = nondiagnostic) and presence of artifacts (5-point scale: 5 = no artifact
      present to 1 = strong impairment). RESULTS: The inherently high signal intensity
      of the renal arterial vasculature in T1w imaging enabled moderate to excellent
      vessel delineation in all sequences. Qualitative (mean, 4.7) and quantitative
      analysis (SNR(mean) : 53.9; CNR(mean) : 28.0) demonstrated the superiority of TOF
      MRA, whereas 2D FLASH imaging provided poorest vessel delineation and was most
      strongly impaired by artifacts (overall impairment 3.7). The 3D FLASH MRI
      demonstrated its potential for fast high quality imaging of the nonenhanced
      arterial vasculature, providing homogeneous hyperintense vessel signal.
      CONCLUSION: Nonenhanced T1w imaging in general and, TOF MRA in particular, appear
      to be promising techniques for good quality nonenhanced renal artery assessment
      at 7 Tesla.

PMID- 22649026
TI  - Quantitative analysis of BDNF/TrkB protein and mRNA in cortical and striatal
      neurons using alpha-tubulin as a normalization factor.
AB  - The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor
      tyrosine kinase TrkB serve important regulatory roles for multiple aspects of the
      biology of neurons including cell death, survival, growth, differentiation, and
      plasticity. Regulation of the local availability of BDNF/TrkB at distinct
      subcellular domains such as soma, dendrites, axons, growth cones, nerve
      terminals, and spines appears to contribute to their specific functions. In view
      of the variance in size and shape of neurons and their compartments, previous
      quantitative studies of the BDNF/TrkB protein and mRNA lacked a robust
      normalization procedure. To overcome this problem, we have established methods
      that use immunofluorescence detection of alpha-tubulin as a normalization factor
      for the quantitative analysis of protein and mRNA in primary rat cortical and
      striatal neurons in culture. The efficacy of this approach is demonstrated by
      studying the dynamic distribution of proteins and mRNA at different growth stages
      or conditions. Treatment of cultured neurons with KCl resulted in increased
      levels of TrkB protein, reduced levels of BDNF mRNA (composite of multiple
      transcripts) and a slight reduction in BDNF protein levels in the dendrites from
      the cortex. The KCl treatment also lowered the percentage of BDNF and TrkB
      proteins in the soma indicative of protein transport. Finally, analysis of the
      rat cortical and striatal neurons demonstrated comparable or even higher levels
      of BDNF/TrkB protein and BDNF mRNA in the neurons from the striatum. Thus, in
      contrast to previous observations made in vivo, striatal neurons are capable of
      synthesizing BDNF mRNA when cultured in growth media in vitro. The analytical
      approach presented here provides a detailed understanding of BDNF/TrkB levels in
      response to a variety of neuronal activities. Our methods could be used broadly,
      including applications in cell and tissue cytometry, to yield accurate
      quantitative data of gene expression in cellular and subcellular contexts. (c)
      2012 International Society for Advancement of Cytometry.

PMID- 22649030
TI  - Cystinosin is a melanosomal protein that regulates melanin synthesis.
AB  - Cystinosis is a rare autosomal recessive disease characterized by cystine crystal
      accumulation leading to multiorgan dysfunctions and caused by mutation in CTNS.
      CTNS encodes cystinosin, a cystine/H(+) symporter that exports cystine out of the
      lysosomes. Patients with cystinosis frequently exhibit blond hair and fair
      complexion, suggesting an alteration in melanogenesis. However, the pigmentation
      singularities of these patients have not been studied, and the role of cystinosin
      in melanogenesis has remained unknown. In our study, a clinical evaluation of 27
      patients with cystinosis showed that 44% had a cutaneous pigmentation dilution
      compared to their relatives. Analysis of the hair melanin content in these
      patients by HPLC demonstrated a 50% decrease in eumelanin (4360 vs. 9360 ng/mg),
      and a 2-fold increase in pheomelanin (53 vs. 20 ng/mg), the yellow/red pigments.
      Cystinosin-deficient mice also showed a 4-fold increase in hair pheomelanin
      content. In vitro studies showed that cystinosin was located at melanosomes. CTNS
      silencing led to a 75% reduction of melanin synthesis that was caused by a
      degradation of tyrosinase by lysosomal proteases. Our results objectify the
      pigmentation defect in patients with cystinosis. We also identify the role of
      CTNS in melanogenesis and add a new gene to the list of the genes involved in the
      control of skin and hair pigmentation.

PMID- 22649032
TI  - Structural and functional insights into lipid-bound nerve growth factors.
AB  - Nerve growth factor (NGF) is a dimeric molecule that modulates the survival,
      proliferation, and differentiation of nervous cells and is also known to act on
      cells of the immune system and endocrine system. NGFs extracted from mouse
      submaxillary gland and cobra venom have different immunological behaviors, yet
      the underlying mechanism remains unclear. Here we report the crystal structure of
      the NGF purified from Chinese cobra Naja naja atra (cNGF), which unexpectedly
      reveals a 2-tailed lipid molecule that is embedded between the two protomers of
      the NGF homodimer. In addition, crystallographic analysis indicated that the
      purified mouse NGF(mNGF) is free from lipid but can bind lysophosphatidylserine
      (lyso-PS) in the same pocket as cNGF. Bioassays indicated that the binding of
      lipid molecules to cNGF and mNGF are essential for their mast cell activation
      activity and abates their p75(NTR) binding capacity. Taken together, these
      results suggest a new mechanism for the regulation of the function of NGF.

PMID- 22649031
TI  - A-kinase anchoring proteins regulate compartmentalized cAMP signaling in airway
      smooth muscle.
AB  - A-kinase anchoring proteins (AKAPs) have emerged as important regulatory
      molecules that can compartmentalize cAMP signaling transduced by beta2-adrenergic
      receptors (beta(2)ARs); such compartmentalization ensures speed and fidelity of
      cAMP signaling and effects on cell function. This study aimed to assess the role
      of AKAPs in regulating global and compartmentalized beta(2)AR signaling in human
      airway smooth muscle (ASM). Transcriptome and proteomic analyses were used to
      characterize AKAP expression in ASM. Stable expression or injection of peptides
      AKAP-IS or Ht31 was used to disrupt AKAP-PKA interactions, and global and
      compartmentalized cAMP accumulation stimulated by beta-agonist was assessed by
      radioimmunoassay and membrane-delineated flow through cyclic nucleotide-gated
      channels, respectively. ASM expresses multiple AKAP family members, with gravin
      and ezrin among the most readily detected. AKAP-PKA disruption had minimal
      effects on whole-cell cAMP accumulation stimulated by beta-agonist (EC(50) and
      B(max)) concentrations, but significantly increased the duration of plasma
      membrane-delineated cAMP (tau=251+/-51 s for scrambled peptide control vs. 399+/
      79 s for Ht31). Direct PKA inhibition eliminated decay of membrane-delineated
      cAMP levels. AKAPs coordinate compartmentalized cAMP signaling in ASM cells by
      regulating multiple elements of beta(2)AR-mediated cAMP accumulation, thereby
      representing a novel target for manipulating beta(2)AR signaling and function in
      ASM.

PMID- 22649034
TI  - Reactivity of nucleosides with a hydroxyl radical in non-aqueous medium.
AB  - DNA damage: The reactivity of HO(.) with silylated 2'-deoxyribonucleosides was
      investigated in acetonitrile by means of a time-resolved technique. The obtained
      rate constants were in general slightly lower than those reported for the natural
      nucleosides in water. Analysis of the reaction mixture by UPLC-MS revealed that
      HO(.) attack occurred at the nucleobase (see scheme).

PMID- 22649033
TI  - Deletion of muscle GRP94 impairs both muscle and body growth by inhibiting local
      IGF production.
AB  - Insulin-like growth factors (IGFs) are critical for development and growth of
      skeletal muscles, but because several tissues produce IGFs, it is not clear which
      source is necessary or sufficient for muscle growth. Because it is critical for
      production of both IGF-I and IGF-II, we ablated glucose-regulated protein 94
      (GRP94) in murine striated muscle to test the necessity of local IGFs for normal
      muscle growth. These mice exhibited smaller skeletal muscles with diminished IGF
      contents but with normal contractile function and no apparent endoplasmic
      reticulum stress response. This result shows that muscles rely on GRP94 primarily
      to support local production of IGFs, a pool that is necessary for normal muscle
      growth. In addition, body weights were ~30% smaller than those of littermate
      controls, and circulating IGF-I also decreased significantly, yet glucose
      homeostasis was maintained with little disruption to the growth hormone pathway.
      The growth defect was complemented on administration of recombinant IGF-I. Thus,
      unlike liver production of IGF-I, muscle IGF-I is necessary not only locally but
      also globally for whole-body growth.

PMID- 22649035
TI  - Negative predictive value for cancer in patients with "gray-zone" PSA level and
      prior negative biopsy: preliminary results with multiparametric 3.0 Tesla MR.
AB  - PURPOSE: To investigate the negative predictive value (NPV) for malignancy of 3.0
      Tesla (T) MRI in patients with "gray zone" PSA level and prior negative biopsies.
      MATERIALS AND METHODS: We enrolled 26 patients with PSA level between 2.5 and 10
      ng/mL and no cancer at previous biopsies. Examinations were performed on a 3.0T
      system using T2-weighted imaging, diffusion-weighted imaging, spectroscopy, and
      postcontrast dynamic study. A regional scheme was used to record MRI findings and
      to perform subsequent transrectal-ultrasonography-guided biopsy. Based on the
      matching between imaging and biopsy findings we estimated MRI predictive values,
      sensitivity, specificity and accuracy on a per-patient and per-region basis.
      RESULTS: On a per patient basis, MRI had five true-positive (5/26; 19.2%), eight
      true-negative (8/26; 30.8%) and no false-negative cases, corresponding to a NPV
      and sensitivity of 100% each. Thirteen patients were assessed as false-positive
      cases (13/26; 50.0%) (specificity of 38.1%). Five of them (5/26; 19.2%) showed
      high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small-acinar
      proliferation (ASAP) at biopsy. T2-weighted imaging alone showed per-region NPV
      (96.8%). CONCLUSION: Because of the high NPV, MRI had the potential to avoid
      unnecessary biopsy in approximately one-third of "gray-zone" patients with a
      negative examination. Additionally, MRI was useful to address to biopsy more than
      one-third of patients with cancer or high-risk lesions as HGPIN and ASAP.

PMID- 22649037
TI  - Vitamin D and inflammatory bowel disease: chicken or egg?

PMID- 22649036
TI  - The double-edged sword of fibronectin in atherosclerosis.

PMID- 22649038
TI  - Stereodefined construction of trisubstituted alkenes by direct coupling reaction
      of allylating agents, alkynes, and organoboranes.
AB  - Tandem reaction: The Pd-catalyzed three-component coupling reaction of an allylic
      alcohol, terminal alkyne, and organoborane to give (E)-1-substituted 2-alkyl-1,4
      pentadienes, involving geminal allylation and alkylation at the acetylenic
      terminal carbon, is described. Bis-diene undergoes a similar multicomponent
      coupling reaction with acetylene and organoborane, involving cyclization of bis
      pi-allylpalladium, to form trans-allyl pentadienyl cyclic and heterocyclic
      compounds with excellent regio- and stereoselectivities (see scheme).

PMID- 22649039
TI  - The generation of variation and the developmental basis for evolutionary novelty.
AB  - Organisms exhibit an incredible diversity of form, a fact that makes the
      evolution of novelty seemingly self-evident. However, despite the "obvious" case
      for novelty, defining this concept in evolutionary terms is highly problematic,
      so much so that some have suggested discarding it altogether. Approaches to this
      problem tend to take either an adaptation- or development-based perspective, but
      we argue here that an exclusive focus on either of these misses the original
      intent of the novelty concept and undermines its practical utility. We propose
      instead that for a feature to be novel, it must have evolved both by a transition
      between adaptive peaks on the fitness landscape and that this transition must
      have overcome a previous developmental constraint. This definition focuses
      novelty on the explanation of apparently difficult or low-probability
      evolutionary transitions and highlights how the integration of developmental and
      functional considerations are necessary to evolutionary explanation. It further
      reinforces that novelty is a central concern not just of evolutionary
      developmental biology (i.e., "evo-devo") but of evolutionary biology more
      generally. We explore this definition of novelty in light of four examples that
      range from the obvious to subtle.

PMID- 22649040
TI  - Pharmacokinetic analysis based on dynamic contrast-enhanced MRI for evaluating
      tumor response to preoperative therapy for oral cancer.
AB  - PURPOSE: To evaluate whether a pharmacokinetic analysis is useful for monitoring
      the response of oral cancer to chemoradiotherapy (CRT). MATERIALS AND METHODS:
      Twenty-nine patients were included. They underwent dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) before and after CRT. The DCE-MRI data were
      analyzed using a Tofts and Kermode (TK) model. The histological evaluation of the
      effects of CRT was performed according to Ohboshi and Shimosato's classification.
      RESULTS: None of the pre-CRT parameters were significantly different between the
      responders and nonresponders. The post-CRT volume of the extravascular
      extracellular space (EES) per unit volume of tissue (v(e) ) of responders (0.397
      +/- 0.080) was higher than that of nonresponders (0.281 +/- 0.076) (P = 0.01).
      The change of the v(e) between the pre- and post-CRT of the responders (0.154 +/-
      0.093) was larger than that of the nonresponders (0.033 +/- 0.073) (P = 0.001).
      Therefore, the increase in the v(e) strongly suggested a good tumor response to
      CRT, which reflected an increase of the EES secondary to the destruction of the
      cancer nest. The changes in the volume transfer constant (K(trans) ) were
      significantly different between the responders and nonresponders (P = 0.018).
      CONCLUSION: Both the increase of the v(e) and the elevation of permeability
      (K(trans) ) were indicative of a good tumor response to CRT. The pharmacokinetic
      analysis had potential for monitoring the histopathological response to CRT.

PMID- 22649041
TI  - Crosstalk between endogenous and synthetic components--synthetic signaling meets
      endogenous components.
AB  - Synthetic biology uses biological components to engineer new functionality in
      living organisms. We have used the tools of synthetic biology to engineer
      detector plants that can sense man-made chemicals, such as the explosive
      trinitrotoluene, and induce a response detectable by eye or instrumentation. A
      goal of this type of work is to make the designed system orthogonal, that is,
      able to function independently of systems in the host. In this review, the design
      and function of two partially synthetic signaling pathways for use in plants is
      discussed. We describe observed interactions (crosstalk) with endogenous
      signaling components. This crosstalk can be beneficial, allowing the creation of
      hybrid synthetic/endogenous signaling pathways, or detrimental, resulting in
      system noise and/or false positives. Current approaches in the field of synthetic
      biology applicable to the design of orthogonal signaling systems, including the
      design of synthetic components, partially synthetic systems that utilize
      crosstalk to signal through endogenous components, computational redesign of
      proteins, and the use of heterologous components, are discussed.

PMID- 22649042
TI  - Assessment and comparison of magnetic nanoparticles as MRI contrast agents in a
      rodent model of human hepatocellular carcinoma.
AB  - The purpose of this study was to synthesize, characterize and tailor the surface
      properties of magnetic nanoparticles with biocompatible copolymer coatings and to
      evaluate the efficiency of the resulting nanoconjugates as magnetic resonance
      imaging (MRI) contrast agents for liver imaging. Magnetic nanoparticles with core
      diameters of 10 and 30 nm were synthesized by pyrolysis and were subsequently
      coated with a copolymer containing either carboxyl (SHP) or methoxy groups as
      termini. All four formulas, and ferumoxides (Feridex I.V.((r))), were
      individually injected intravenously into separate, normal Balb/C mice (at 2.5,
      1.0 and 0.56 mg Fe kg(-1)), and the animals underwent T(2)-weighted MRI at
      multiple time points post injection (p.i.) to evaluate the hepatic uptake and
      clearance. Furthermore, we compared the abilities of the new formulas and Feridex
      to detect tumors in an orthotropic Huh7 tumor model. Transmission electron
      microscopy (TEM) revealed a narrow size distribution of both the 10 and 30 nm
      nanoparticles, in contrast to a wide size distribution of Feridex. MTT, apoptosis
      and cyclin/DNA flow cytometry assays showed that the polymer coated nanoparticles
      had no adverse effect on cell growth. Among all the tested formulas, including
      Feridex, SHP-30 showed the highest macrophage uptake at the in vitro level. In
      vivo MRI studies on normal mice confirmed the superiority of SHP-30 in inducing
      hypointensities in the liver tissue, especially at clinical dose (0.56 mg Fe kg(
      1)) and 3 T field. SHP-30 showed better contrast-to-noise ratio than Feridex on
      the orthotropic Huh7 tumor model. SHP-30 was found to be an efficient contrast
      agent for liver MR imaging. The success of this study suggests that, by improving
      the synthetic approach and by tuning the surface properties of IONPs, one can
      arrive at better formulas than Feridex for clinical practice.

PMID- 22649043
TI  - How cellular processing of superparamagnetic nanoparticles affects their magnetic
      behavior and NMR relaxivity.
AB  - Cellular processing of nanomaterials may affect their physical properties at the
      root of various biomedical applications. When nanoparticles interact with living
      cells, their spatial distribution is progressively modified by cellular activity,
      which tends to concentrate them into intracellular compartments, changing in turn
      their responsivity to physical stimuli. In this paper, we investigate the
      consequences of cellular uptake on the related magnetic properties and NMR
      relaxivity of iron oxide nanoparticles. The superparamagnetic behavior (field
      dependent and temperature-dependent magnetization curves investigated by SQUID
      (Superconducting Quantum Interference Device) measurements) and nuclear magnetic
      relaxation dispersion (NMRD) R(1) profiles of citrate-coated maghemite
      nanoparticles (mean diameter 8 nm) were characterized in colloidal suspension and
      after being uptaken by several types of cells (tumor cells, stem cells and
      macrophages). The temperature-dependent magnetization as well as the NMRD profile
      were changed following cellular uptake depending on the stage of endocytosis
      process while the field-dependent magnetization at room temperature remained
      unchanged. Magnetic coupling between nanoparticles confined in cell lysosomes
      accounts for the modification in magnetic behavior, thereby reflecting the local
      organization of nanoparticles. NMR longitudinal relaxivity was directly sensitive
      to the intracellular distribution of nanoparticles, in line with Transmission
      Electron Microscopy TEM observations. This study is the first attempt to link up
      magnetic properties and NMR characterization of iron oxide nanoparticles before
      and after their cell processing.

PMID- 22649044
TI  - Improved measurement of labile proton concentration-weighted chemical exchange
      rate (k(ws)) with experimental factor-compensated and T(1) -normalized
      quantitative chemical exchange saturation transfer (CEST) MRI.
AB  - Chemical exchange saturation transfer (CEST) MRI enables measurement of dilute
      CEST agents and microenvironment properties such as pH and temperature, holding
      great promise for in vivo applications. However, because of confounding
      concomitant radio frequency (RF) irradiation and relaxation effects, the CEST
      weighted MRI contrast may not fully characterize the underlying CEST phenomenon.
      We postulated that the accuracy of quantitative CEST MRI could be improved if the
      experimental factors (labeling efficiency and RF spillover effect) were estimated
      and taken into account. Specifically, the experimental factor was evaluated as a
      function of exchange rate and CEST agent concentration ratio, which remained
      relatively constant for intermediate RF irradiation power levels. Hence, the
      experimental factors can be calculated based on the reasonably estimated exchange
      rate and labile proton concentration ratio, which significantly improved
      quantification. The simulation was confirmed with creatine phantoms of serially
      varied concentration titrated to the same pH, whose reverse exchange rate (k(ws))
      was found to be linearly correlated with the concentration. In summary, the
      proposed solution provides simplified yet reasonably accurate quantification of
      the underlying CEST system, which may help guide the ongoing development of
      quantitative CEST MRI.

PMID- 22649045
TI  - Fast clearing RGD-based near-infrared fluorescent probes for in vivo tumor
      diagnosis.
AB  - A fast clearing hydrophilic near-infrared (NIR) dye ICG-Der-02 was used to
      constitute tumor targeting contrast agents. Cell adhesion molecule integrin
      alpha(v)beta(3) served as the target receptor because of its unique expression on
      almost all sprouting tumor vasculatures. The purpose of this study was to
      synthesize and compare the properties of integrin alpha(v)beta(3)-targeted, fast
      clearing NIR probes both in vitro and in vivo for tumor diagnosis. ICG-Der-02 was
      covalently conjugated to three kinds of RGD peptide including linear, monoeric
      cyclic and dimeric RGD to form three RGD-based NIR probes. The integrin receptor
      specificities of these probes were evaluated in vitro by confocal microscopy. The
      dynamic bio-distribution and elimination ratse were in vivo real-time monitored
      by a near-infrared imaging system in normal mice. Further, the in vivo tumor
      targeting abilities of the RGD-based NIR probes were compared in alpha(v)beta(3) 
      positive MDA-MB-231, U87MG and alpha(v)beta(3)-negtive MCF-7 xenograft mice
      models. Three RGD-based NIR probes were successfully synthesized with good
      optical properties. In vitro cellular experiments indicated that the probes have
      a clear binding affinity to alpha(upsilon)beta(3) -positive tumor cells, with a
      cyclic dimeric RGD probe owing the highest integrin affinity. Dynamic bio
      distributions of these probes showed a rapid clearing rate through the renal
      pathway. In vivo tumor targeting ability of the RGD-based porbes was demonstrated
      on MDA-MB-231 and U87MG tumor models. As expected, the c(RGDyK)(2)-ICG-Der-02
      probe displayed the highest tumor-to-normal tissue contrast. The in vitro and in
      vivo block experiments confirmed the receptor binding specificity of the probes.
      The hydrophilic dye-labeled NIR probes exhibited a fast clearing rate and deep
      tissue penetration capability. Further, the alpha(upsilon)beta(3) receptor
      affinity of the three RGD-based NIR probes followed the order of dimer cyclic >
      monomer cyclic > linear. The results demonstrate potent fast clearing probes for
      in vivo early tumor diagnosis.

PMID- 22649046
TI  - Labelling of olfactory ensheathing cells with micron-sized particles of iron
      oxide and detection by MRI.
AB  - A crucial issue in transplant-mediated repair of the damaged central nervous
      system (CNS) is serial non-invasive imaging of the transplanted cells, which has
      led to interest in the application of magnetic resonance imaging (MRI) combined
      with designated intracellular magnetic labels for cell tracking. Micron-sized
      particles of iron oxide (MPIO) have been successfully used to track cells by MRI,
      yet there is relatively little known about either their suitability for efficient
      labelling of specific cell types, or their effects on cell viability. The purpose
      of this study was to develop a suitable MPIO labelling protocol for olfactory
      ensheathing cells (OECs), a type of glia used to promote the regeneration of CNS
      axons after transplantation into the injured CNS. Here, we demonstrate an OEC
      labelling efficiency of >90% with an MPIO incubation time as short as 6 h,
      enabling intracellular particle uptake for single-cell detection by MRI without
      affecting cell proliferation, migration and viability. Moreover, MPIO are
      resolvable in OECs transplanted into the vitreous body of adult rat eyes,
      providing the first detailed protocol for efficient and safe MPIO labelling of
      OECs for non-invasive MRI tracking of transplanted OECs in real time for use in
      studies of CNS repair and axon regeneration.

PMID- 22649047
TI  - Toward absolute quantification of iron oxide nanoparticles as well as cell
      internalized fraction using multiparametric MRI.
AB  - Iron oxide nanoparticles (IONPs) are widely used as MR contrast agents because of
      their strong magnetic properties and broad range of applications. The contrast
      induced by IONPs typically depends on concentration, water accessibility,
      particle size and heterogeneity of IONP distribution within the microenvironment.
      Although the latter could be a tool to assess local physiological effects at the
      molecular level, it renders IONP quantification from relaxation measurements
      challenging. This study aims to quantify IONP concentration using susceptibility
      measurements. In addition, further analysis of relaxation data is proposed to
      extract quantitative information about the IONP spatial distribution. Mesenchymal
      stem cells were labeled with IONPs and the IONP concentration measured by mass
      spectroscopy. MR relaxation parameters (T(1), T(2), T(2)*) as well as magnetic
      susceptibility of cylindrical samples containing serial dilutions of mixtures of
      free and cell-internalized IONPs were measured and correlated with IONP
      concentration. Unlike relaxation data, magnetic susceptibility was independent of
      whether IONPs were free or internalized, making it an excellent candidate for
      IONP quantification. Using IONP concentration derived from mass spectroscopy and
      measured relaxation times, free and internalized IONP fractions were accurately
      calculated. Magnetic susceptibility was shown to be a robust technique to measure
      IONP concentration in this preliminary study. Novel imaging-based susceptibility
      mapping techniques could prove to be valuable tools to quantify IONP
      concentration directly by MRI, for samples of arbitrary shape. Combined with
      relaxation time mapping techniques, especially T(2) and T(2)*, this could be an
      efficient way to measure both IONP concentration and the internalized IONP
      fraction in vivo using MRI, to gain insight into tissue function and molecular
      imaging paradigms.

PMID- 22649048
TI  - The serial effect of iodinated contrast media on renal hemodynamics and
      oxygenation as evaluated by ASL and BOLD MRI.
AB  - Contrast-induced nephropathy is a prevalent cause of renal failure, and the
      mechanisms underlying this injury are not fully understood. We utilized
      noninvasive functional MRI in order to determine the serial effect of a single
      administration of iodinated contrast media (CM) on renal hemodynamics and
      oxygenation. Fifteen rabbits were randomized to receive an intravenous injection
      of CM (i.e. iopamidol-370; 6 ml kg(-1) body weight) or an equivalent amount of
      0.9% saline. Both arterial spin-labeling and blood oxygen level-dependent imaging
      sequences were performed at 24 h before and at intervals of 1, 24, 48 and 72 h
      after injection to obtain serial renal blood flow (RBF) and relative spin-spin
      relaxation rate (R(2)*). Results showed that, in the iopamidol group, the mean
      cortical RBF decreased at 1 h (p = 0.04 vs baseline), reached its minimum at 24 h
      (p = 0.01) and gradually returned to baseline by 48 h (p = nonsignificant, NS).
      The outer medullary RBF decreased to its minimum by 24 h (p = 0.00) and remained
      less than baseline until 72 h. R(2)* in inner stripes was dramatically increased
      at 1 h (p = 0.00), remained elevated at 24 h (p = 0.05), but returned to baseline
      by 48 h (p = NS). R(2)* values within the cortex and outer stripes and inner
      medulla were slightly increased, but the changes did not reach a statistical
      significance (p = NS). Saline did not produce positive change in either RBF or
      R(2)* within different compartments of the kidney. We conclude that iopamidol is
      associated with a relatively longer-term hypoperfusion in whole kidney and
      decreased oxygen level in the inner stripes of the outer medulla.

PMID- 22649049
TI  - Evaluation of manganese uptake and toxicity in mouse brain during continuous
      MnCl2 administration using osmotic pumps.
AB  - Manganese is a vital element and cofactor of many key enzymes, but it is toxic at
      high levels, causing pronounced disturbances in the mammalian brain. Magnetic
      resonance imaging (MRI) studies using manganese ions as a paramagnetic contrast
      agent are often limited by the neurotoxicity of Mn(2+) . In this work, we have
      explored a new in vivo model to study Mn(2+) uptake, distribution and
      neurotoxicity in mice by subcutaneous implantation of mini-osmotic pumps
      delivering MnCl(2) continuously for 21 days. Fractionated injections can reduce
      the toxicity; however, constant administration at very low doses using osmotic
      pumps caused a substantial effect on the T(1) contrast in MRI while reducing
      toxicity. Manganese-enhanced MRI documented fast but reversible Mn(2+) deposition
      largely in glomerular and mitral cell layers of the olfactory bulb, in the CA3
      area of the hippocampus, and in the gray matter of the cerebellum. Mn(2+)
      accumulated as early as the first days after implantation, with a fast dispersal
      9 days after stopping a 12-days Mn(2+) exposure. Prominent Mn(2+) accumulation
      was also seen in salivary glands and in the endocrine thyroid and posterior
      pituitary gland. These structures with enhanced Mn(2+) accumulation correlated
      well with those showing high expression of the secretory pathway Ca(2+) /Mn(2+) 
      ATPase (SPCA1), i.e. a transporter that could take part in Mn(2+) detoxification.
      Our new experimental model for continuous low-dosage administration of Mn(2+) is
      an easy alternative for enhancing Mn(2+) -based contrast in MEMRI studies, and
      might provide insight into the etiology of neuropathologies resulting from
      chronic Mn(2+) exposure in vivo.

PMID- 22649050
TI  - Superparamagnetic iron oxide nanoparticles conjugated to a grass pollen allergen
      and an optical probe.
AB  - In this study we report the development of a bioconjugate between
      superparamagnetic iron oxide nanoparticles and Phl p5a (one of the major
      allergens from grass pollen). The bioconjugate also contains an optical probe
      (Alexa647) conjugated to the nanoparticle via biotin-streptavidin association. We
      show that this conjugate has a range of features that makes it a very promising
      candidate to image the localization of this allergen in vivo: (a) upon
      conjugation to the iron oxide nanoparticles, the allergen retains its ability to
      interact with IgE antibodies; (b) the magnetic properties of the iron oxide core
      of this bioconjugate are suitable for MR imaging; and (c) Alexa647 fluorophore
      retains its emission properties once attached to the iron oxide nanoparticles,
      yielding a dual modality MRI-optical probe.

PMID- 22649052
TI  - Contextualizing context for synthetic biology--identifying causes of failure of
      synthetic biological systems.
AB  - Despite the efforts that bioengineers have exerted in designing and constructing
      biological processes that function according to a predetermined set of rules,
      their operation remains fundamentally circumstantial. The contextual situation in
      which molecules and single-celled or multi-cellular organisms find themselves
      shapes the way they interact, respond to the environment and process external
      information. Since the birth of the field, synthetic biologists have had to
      grapple with contextual issues, particularly when the molecular and genetic
      devices inexplicably fail to function as designed when tested in vivo. In this
      review, we set out to identify and classify the sources of the unexpected
      divergences between design and actual function of synthetic systems and analyze
      possible methodologies aimed at controlling, if not preventing, unwanted
      contextual issues.

PMID- 22649053
TI  - Multimodal photoacoustic ophthalmoscopy in mouse.
AB  - Photoacoustic ophthalmoscopy (PAOM) is a novel imaging technology that measures
      optical absorption in the retina. The capability of PAOM can be further enhanced
      if it could image mouse eyes, because mouse models are widely used for various
      retinal diseases. The challenges in achieving high-quality imaging of mouse
      retina, however, come from the much smaller eyeball size. Here, we report an
      optimized imaging system, which integrates PAOM, spectral-domain optical
      coherence tomography (SD-OCT), and autofluorescence-scanning laser ophthalmoscopy
      (AF-SLO), for mouse eyes. Its multimodal capability was demonstrated by imaging
      transgenic Nrl-GFP mice that express green fluorescent protein (GFP) in
      photoreceptors. SD-OCT provided guidance of optical alignment for PAOM and AF
      SLO, and complementary contrast with high depth-resolution retinal cross
      sections. PAOM visualized the retinal vasculature and retinal pigment epithelium
      melanin, and AF-SLO measured GFP-expressing in retinal photoreceptors. The in
      vivo imaging results were verified by histology and confocal microscopy.

PMID- 22649054
TI  - Impact of methylations of m2G966/m5C967 in 16S rRNA on bacterial fitness and
      translation initiation.
AB  - The functional centers of the ribosome in all organisms contain ribosomal RNA
      (rRNA) modifications, which are introduced by specialized enzymes and come at an
      energy cost for the cell. Surprisingly, none of the modifications tested so far
      was essential for growth and hence the functional role of modifications is
      largely unknown. Here, we show that the methyl groups of nucleosides m(2)G966 and
      m(5)C967 of 16S rRNA in Escherichia coli are important for bacterial fitness. In
      vitro analysis of all phases of translation suggests that the m(2)G966/m(5)C967
      modifications are dispensable for elongation, termination and ribosome recycling.
      Rather, the modifications modulate the early stages of initiation by stabilizing
      the binding of fMet-tRNA(fMet) to the 30S pre-initiation complex prior to start
      codon recognition. We propose that the m(2)G966 and m(5)C967 modifications help
      shaping the bacterial proteome, most likely by fine-tuning the rates that
      determine the fate of a given messenger RNA (mRNA) at early checkpoints of mRNA
      selection.

PMID- 22649055
TI  - Fidelity of capture-enrichment for mtDNA genome sequencing: influence of NUMTs.
AB  - Enriching target sequences in sequencing libraries via capture hybridization to
      bait/probes is an efficient means of leveraging the capabilities of next
      generation sequencing for obtaining sequence data from target regions of
      interest. However, homologous sequences from non-target regions may also be
      enriched by such methods. Here we investigate the fidelity of capture enrichment
      for complete mitochondrial DNA (mtDNA) genome sequencing by analyzing sequence
      data for nuclear copies of mtDNA (NUMTs). Using capture-enriched sequencing data
      from a mitochondria-free cell line and the parental cell line, and from samples
      previously sequenced from long-range PCR products, we demonstrate that NUMT
      alleles are indeed present in capture-enriched sequence data, but at low enough
      levels to not influence calling the authentic mtDNA genome sequence. However,
      distinguishing NUMT alleles from true low-level mutations (e.g. heteroplasmy) is
      more challenging. We develop here a computational method to distinguish NUMT
      alleles from heteroplasmies, using sequence data from artificial mixtures to
      optimize the method.

PMID- 22649056
TI  - IntScore: a web tool for confidence scoring of biological interactions.
AB  - Knowledge of all molecular interactions that potentially take place in the cell
      is a key for a detailed understanding of cellular processes. Currently available
      interaction data, such as protein-protein interaction maps, are known to contain
      false positives that inevitably diminish the accuracy of network-based
      inferences. Interaction confidence scoring is thus a crucial intermediate step
      after obtaining interaction data and before using it in an interaction network
      based inference approach. It enables to weight individual interactions according
      to the likelihood that they actually take place in the cell, and can be used to
      filter out false positives. We describe a web tool called IntScore which
      calculates confidence scores for user-specified sets of interactions. IntScore
      provides six network topology- and annotation-based confidence scoring methods.
      It also enables the integration of scores calculated by the different methods
      into an aggregate score using machine learning approaches. IntScore is user
      friendly and extensively documented. It is freely available at
      http://intscore.molgen.mpg.de.

PMID- 22649057
TI  - idTarget: a web server for identifying protein targets of small chemical
      molecules with robust scoring functions and a divide-and-conquer docking
      approach.
AB  - Identification of possible protein targets of small chemical molecules is an
      important step for unravelling their underlying causes of actions at the
      molecular level. To this end, we construct a web server, idTarget, which can
      predict possible binding targets of a small chemical molecule via a divide-and
      conquer docking approach, in combination with our recently developed scoring
      functions based on robust regression analysis and quantum chemical charge models.
      Affinity profiles of the protein targets are used to provide the confidence
      levels of prediction. The divide-and-conquer docking approach uses adaptively
      constructed small overlapping grids to constrain the searching space, thereby
      achieving better docking efficiency. Unlike previous approaches that screen
      against a specific class of targets or a limited number of targets, idTarget
      screen against nearly all protein structures deposited in the Protein Data Bank
      (PDB). We show that idTarget is able to reproduce known off-targets of drugs or
      drug-like compounds, and the suggested new targets could be prioritized for
      further investigation. idTarget is freely available as a web-based server at
      http://idtarget.rcas.sinica.edu.tw.

PMID- 22649058
TI  - Heterochromatin protein 1 gamma and IkappaB kinase alpha interdependence during
      tumour necrosis factor gene transcription elongation in activated macrophages.
AB  - IkappaB kinase alpha (IKKalpha) is part of the cytoplasmic IKK complex regulating
      nuclear factor-kappaB (NF-kappaB) release and translocation into the nucleus in
      response to pro-inflammatory signals. IKKalpha can also be recruited directly to
      the promoter of NF-kappaB-dependent genes by NF-kappaB where it phosphorylates
      histone H3 at serine 10, triggering recruitment of the bromodomain-containing
      protein 4 and the positive transcription elongation factor b. Herein, we report
      that IKKalpha travels with the elongating form of ribonucleic acid polymerase II
      together with heterochromatin protein 1 gamma (HP1gamma) at NF-kappaB-dependent
      genes in activated macrophages. IKKalpha binds to and phosphorylates HP1gamma,
      which in turn controls IKKalpha binding to chromatin and phosphorylation of the
      histone variant H3.3 at serine 31 within transcribing regions. Downstream of
      transcription end sites, IKKalpha accumulates with its inhibitor the CUE-domain
      containing protein 2, suggesting a link between IKKalpha inactivation and
      transcription termination.

PMID- 22649059
TI  - DIANA miRPath v.2.0: investigating the combinatorial effect of microRNAs in
      pathways.
AB  - MicroRNAs (miRNAs) are key regulators of diverse biological processes and their
      functional analysis has been deemed central in many research pipelines. The new
      version of DIANA-miRPath web server was redesigned from the ground-up. The user
      of DNA Intelligent Analysis (DIANA) DIANA-miRPath v2.0 can now utilize miRNA
      targets predicted with high accuracy based on DIANA-microT-CDS and/or
      experimentally verified targets from TarBase v6; combine results with merging and
      meta-analysis algorithms; perform hierarchical clustering of miRNAs and pathways
      based on their interaction levels; as well as elaborate sophisticated
      visualizations, such as dendrograms or miRNA versus pathway heat maps, from an
      intuitive and easy to use web interface. New modules enable DIANA-miRPath server
      to provide information regarding pathogenic single nucleotide polymorphisms
      (SNPs) in miRNA target sites (SNPs module) or to annotate all the predicted and
      experimentally validated miRNA targets in a selected molecular pathway (Reverse
      Search module). DIANA-miRPath v2.0 is an efficient and yet easy to use tool that
      can be incorporated successfully into miRNA-related analysis pipelines. It
      provides for the first time a series of highly specific tools for miRNA-targeted
      pathway analysis via a web interface and can be accessed at
      http://www.microrna.gr/miRPathv2.

PMID- 22649060
TI  - GalaxyWEB server for protein structure prediction and refinement.
AB  - Three-dimensional protein structures provide invaluable information for
      understanding and regulating biological functions of proteins. The GalaxyWEB
      server predicts protein structure from sequence by template-based modeling and
      refines loop or terminus regions by ab initio modeling. This web server is based
      on the method tested in CASP9 (9th Critical Assessment of techniques for protein
      Structure Prediction) as 'Seok-server', which was assessed to be among top
      performing template-based modeling servers. The method generates reliable core
      structures from multiple templates and re-builds unreliable loops or termini by
      using an optimization-based refinement method. In addition to structure
      prediction, a user can also submit a refinement only job by providing a starting
      model structure and locations of loops or termini to refine. The web server can
      be freely accessed at http://galaxy.seoklab.org/.

PMID- 22649061
TI  - Amplification-free whole-genome bisulfite sequencing by post-bisulfite adaptor
      tagging.
AB  - DNA methylation plays a key role in epigenetic regulation of eukaryotic genomes.
      Hence the genome-wide distribution of 5-methylcytosine, or the methylome, has
      been attracting intense attention. In recent years, whole-genome bisulfite
      sequencing (WGBS) has enabled methylome analysis at single-base resolution.
      However, WGBS typically requires microgram quantities of DNA as well as global
      PCR amplification, thereby precluding its application to samples of limited
      amounts. This is presumably because bisulfite treatment of adaptor-tagged
      templates, which is inherent to current WGBS methods, leads to substantial DNA
      fragmentation. To circumvent the bisulfite-induced loss of intact sequencing
      templates, we conceived an alternative method termed Post-Bisulfite Adaptor
      Tagging (PBAT) wherein bisulfite treatment precedes adaptor tagging by two rounds
      of random primer extension. The PBAT method can generate a substantial number of
      unamplified reads from as little as subnanogram quantities of DNA. It requires
      only 100 ng of DNA for amplification-free WGBS of mammalian genomes. Thus, the
      PBAT method will enable various novel applications that would not otherwise be
      possible, thereby contributing to the rapidly growing field of epigenomics.

PMID- 22649062
TI  - Brain metabolite alterations and cognitive dysfunction in early Huntington's
      disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder characterized by early
      cognitive decline that progresses at later stages to dementia and severe movement
      disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion
      mutation in the Huntingtin gene, allowing early diagnosis by genetic testing.
      This study aimed to identify the relationship of N-acetylaspartate and other
      brain metabolites to cognitive function in HD-mutation carriers by using high
      field-strength magnetic resonance spectroscopy (MRS) at 7 Tesla. Twelve
      individuals with the HD mutation in premanifest or early-stage disease versus 12
      healthy controls underwent (1)H magnetic resonance spectroscopy (7.2 mL voxel in
      the posterior cingulate cortex) at 7 Tesla, and also T1-weighted structural
      magnetic resonance imaging. All participants received standardized tests of
      cognitive functioning including the Montreal Cognitive Assessment and
      standardized quantified neurological examination within an hour before scanning.
      Individuals with the HD mutation had significantly lower posterior cingulate
      cortex N-acetylaspartate (-9.6%, P = .02) and glutamate (-10.1%, P = .02) levels
      than did controls. In contrast, in this small group, measures of brain morphology
      including striatal and ventricle volumes did not differ significantly. Linear
      regression with Montreal Cognitive Assessment scores revealed significant
      correlations with N-acetylaspartate (r(2) = 0.50, P = .01) and glutamate (NAA)
      (r(2) = 0.64, P = .002) in HD subjects. Our data suggest a relationship between
      reduced N-acetylaspartate and glutamate levels in the posterior cingulate cortex
      with cognitive decline in the early stages of HD. N-acetylaspartate and glutamate
      magnetic resonance spectroscopy signals of the posterior cingulate cortex region
      may serve as potential biomarkers of disease progression or treatment outcome in
      HD and other neurodegenerative disorders with early cognitive dysfunction, when
      structural brain changes are still minor.

PMID- 22649063
TI  - Magnetic resonance imaging of the substantia nigra in Parkinson's disease.
AB  - Until recently, conventional magnetic resonance imaging (MRI) was most often
      negative in Parkinson's disease or showed nonspecific findings. Recent
      developments in structural MRI, including relaxometry, magnetization transfer,
      and neuromelanin imaging, have demonstrated improved contrast and enabled more
      accurate visualization of deep brain nuclei, in particular, the substantia nigra.
      Meanwhile, diffusion imaging has provided useful biomarkers of substantia nigra
      degeneration, showing reduced anisotropy and anatomical connectivity with the
      striatum and thalamus. These advances in structural imaging are complemented by
      findings of magnetic resonance spectroscopy on brain metabolism and resting-state
      functional MRI on functional connectivity. This article presents an overview of
      these new structural, metabolic, and resting-state functional MRI techniques and
      their implications for Parkinson's disease. The techniques are reviewed in the
      context of their potential for better understanding the disease in terms of
      diagnosis and pathophysiology and as biomarkers of its progression.

PMID- 22649064
TI  - Deficient leukemia inhibitory factor signaling in muscle precursor cells from
      patients with type 2 diabetes.
AB  - The cytokine leukemia-inhibitory factor (LIF) is expressed by skeletal muscle and
      induces proliferation of muscle precursor cells, an important feature of skeletal
      muscle maintenance and repair. We hypothesized that muscle precursor cells from
      patients with type 2 diabetes had a deficient response to LIF. The mRNA and
      protein expressions of LIF and its receptor (LIFR) were measured in skeletal
      muscle biopsies from healthy individuals and patients with type 2 diabetes by use
      of qPCR and Western blot. LIF signaling and response were studied following
      administration of recombinant LIF and siRNA knockdown of suppressor of cytokine
      signaling (SOCS)3 in myoblast cultures established from healthy individuals and
      patients with type 2 diabetes. Myoblast proliferation rate was assessed by
      bromodeoxyuridine incorporation. LIF and LIFR proteins were increased in both
      muscle tissue and cultured myoblasts from diabetic patients. Nonetheless, in the
      diabetic myoblasts, LIF-induced phosphorylation of signal transducer and
      activator of transcription (STAT)1 and STAT3 was impaired. The deficient response
      to LIF administration in the diabetic myoblasts was further emphasized by a lack
      of increase in LIF-stimulated cell proliferation and a decreased LIF-stimulated
      induction of the proliferation-promoting factors cyclin D1, JunB, and c-myc.
      SOCS3 protein was upregulated in diabetic myoblasts, and knockdown of SOCS3
      rescued LIF-induced gene expression in diabetic myoblasts, whereas neither STAT1
      or STAT3 signaling nor proliferation rate was affected. In conclusion, although
      LIF and LIFR proteins were increased in muscle tissue and myoblasts from diabetic
      patients, LIF signaling and LIF-stimulated cell proliferation were impaired in
      diabetic myoblasts, suggesting a novel mechanism by which muscle function is
      compromised in diabetes.

PMID- 22649066
TI  - Acute supplementation of amino acids increases net protein accretion in IUGR
      fetal sheep.
AB  - Placental insufficiency decreases fetal amino acid uptake from the placenta,
      plasma insulin concentrations, and protein accretion, thus compromising normal
      fetal growth trajectory. We tested whether acute supplementation of amino acids
      or insulin into the fetus with intrauterine growth restriction (IUGR) would
      increase net fetal protein accretion rates. Late-gestation IUGR and control (CON)
      fetal sheep received acute, 3-h infusions of amino acids (with euinsulinemia),
      insulin (with euglycemia and euaminoacidemia), or saline. Fetal leucine
      metabolism was measured under steady-state conditions followed by a fetal muscle
      biopsy to quantify insulin signaling. In CON, increasing amino acid delivery
      rates to the fetus by 100% increased leucine oxidation rates by 100%. In IUGR,
      amino acid infusion completely suppressed fetal protein breakdown rates but
      increased leucine oxidation rate by only 25%, resulting in increased protein
      accretion rates by 150%. Acute insulin infusion, however, had very little effect
      on amino acid delivery rates, fetal leucine disposal rates, or fetal protein
      accretion rates in CON or IUGR fetuses despite robust signaling of the fetal
      skeletal muscle insulin-signaling cascade. These results indicate that, when
      amino acids are given directly into the fetal circulation independently of
      changes in insulin concentrations, IUGR fetal sheep have suppressed protein
      breakdown rates, thus increasing net fetal protein accretion.

PMID- 22649065
TI  - Gene regulation of UDP-galactose synthesis and transport: potential rate-limiting
      processes in initiation of milk production in humans.
AB  - Lactose synthesis is believed to be rate limiting for milk production. However,
      understanding the molecular events controlling lactose synthesis in humans is
      still rudimentary. We have utilized our established model of the RNA isolated
      from breast milk fat globule from seven healthy, exclusively breastfeeding women
      from 6 h to 42 days following delivery to determine the temporal coordination of
      changes in gene expression in the carbohydrate metabolic processes emphasizing
      the lactose synthesis pathway in human mammary epithelial cell. We showed that
      milk lactose concentrations increased from 75 to 200 mM from 6 to 96 h. Milk
      progesterone concentrations fell by 65% at 24 h and were undetectable by day 3.
      Milk prolactin peaked at 36 h and then declined progressively afterward. In
      concordance with lactose synthesis, gene expression of galactose kinase 2, UDP
      glucose pyrophosphorylase 2 (UGP2), and phosphoglucomutase 1 increased 18-, 10-,
      and threefold, respectively, between 6 and 72 h. Between 6 and 96 h, gene
      expression of UDP-galactose transporter 2 (SLC35A2) increased threefold, whereas
      glucose transporter 1 was unchanged. Gene expression of lactose synthase no. 3
      increased 1.7-fold by 96 h, whereas alpha-lactalbumin did not change over the
      entire study duration. Gene expression of prolactin receptor (PRLR) and its
      downstream signal transducer and activator of transcription complex 5 (STAT5)
      were increased 10- and 2.5-fold, respectively, by 72 h. In summary, lactose
      synthesis paralleled the induction of gene expression of proteins involved in UDP
      galactose synthesis and transport, suggesting that they are potentially rate
      limiting in lactose synthesis and thus milk production. Progesterone withdrawal
      may be the signal that triggers PRLR signaling via STAT5, which may in turn
      induce UGP2 and SLC35A2 expression.

PMID- 22649067
TI  - Assessment of body cell mass at bedside in critically ill patients.
AB  - Critical illness affects body composition profoundly, especially body cell mass
      (BCM). BCM loss reflects lean tissue wasting and could be a nutritional marker in
      critically ill patients. However, BCM assessment with usual isotopic or tracer
      methods is impractical in intensive care units (ICUs). We aimed to modelize the
      BCM of critically ill patients using variables available at bedside. Fat-free
      mass (FFM), bone mineral (Mo), and extracellular water (ECW) of 49 critically ill
      patients were measured prospectively by dual-energy X-ray absorptiometry and
      multifrequency bioimpedance. BCM was estimated according to the four-compartment
      cellular level: BCM = FFM - (ECW/0.98) - (0.73 * Mo). Variables that might
      influence the BCM were assessed, and multivariable analysis using fractional
      polynomials was conducted to determine the relations between BCM and these data.
      Bootstrap resampling was then used to estimate the most stable model predicting
      BCM. BCM was 22.7 +/- 5.4 kg. The most frequent model included height (cm), leg
      circumference (cm), weight shift (Delta) between ICU admission and body
      composition assessment (kg), and trunk length (cm) as a linear function: BCM (kg)
      = 0.266 * height + 0.287 * leg circumference + 0.305 * Deltaweight - 0.406 *
      trunk length - 13.52. The fraction of variance explained by this model (adjusted
      r(2)) was 46%. Including bioelectrical impedance analysis variables in the model
      did not improve BCM prediction. In summary, our results suggest that BCM can be
      estimated at bedside, with an error lower than +/-20% in 90% subjects, on the
      basis of static (height, trunk length), less stable (leg circumference), and
      dynamic biometric variables (Deltaweight) for critically ill patients.

PMID- 22649068
TI  - Treatment with constitutive androstane receptor ligand during pregnancy prevents
      insulin resistance in offspring from high-fat diet-induced obese pregnant mice.
AB  - The constitutive androstane receptor (CAR) has been reported to decrease insulin
      resistance even during pregnancy, while exposure to a high-fat diet (HFD) in
      utero in mice can induce a type 2 diabetes phenotype that can be transmitted to
      the progeny. Therefore, we examined whether treatment with a CAR ligand during
      pregnancy could prevent hypertension, insulin resistance, and hyperlipidemia in
      the offspring from HFD-induced obese pregnant mice (OH mice). We employed four
      groups of offspring from HFD-fed and control diet-fed pregnant mice with or
      without treatment with a CAR ligand. Treatment with a CAR ligand during pregnancy
      improved glucose tolerance and the levels of triglyceride and adipocytokine and
      restored the changes induced by HFD with amelioration of hypertension in the
      adult OH mice. This treatment also increased adiponectin mRNA expression,
      suppressed leptin expression in adipose tissues of OH mice, and abolished the
      effect of HFD on the epigenetic modifications of the genes encoding adiponectin
      and leptin in the offspring during immaturity and adulthood. Our data suggest
      that CAR might be a potential therapeutic target to prevent metabolic syndrome in
      adulthood of offspring exposed to an HFD in utero.

PMID- 22649070
TI  - Male mice produced by in vitro culture have reduced fertility and transmit
      organomegaly and glucose intolerance to their male offspring.
AB  - It has been reported that suboptimal in vitro culture (IVC) of mouse embryos can
      affect the postnatal expression of epigenetically sensitive alleles, resulting in
      altered postnatal growth, organ dimensions, health, and behavior in the
      offspring. Although these detrimental impacts on the offspring are well
      described, the relative contribution of the IVC-produced fathers is unclear. In
      this work, we have analyzed if suboptimal IVC (achieved by altering the culture
      medium by the addition of FCS) can affect male fertility and if organ size and
      glucose clearance, two of the adverse effects produced by suboptimal IVC
      conditions, were transmitted to the next two generations. IVC-produced males had
      lower sperm concentrations (5.8 * 10(6) spermatozoa in IVC vs. 14.5 * 10(6)
      spermatozoa in control), and these sperm exhibited decreased overall motility
      (49.6% vs. 72.8% in control) and progressive motility (22.6% vs. 32.2% in
      control). Fertility tests demonstrated that the percentage of pregnancies was
      reduced for IVC males (35% for IVC-produced males vs. 86% for in vivo controls).
      These features were related to a modified gene expression pattern in adult male
      testes, showing an altered gene expression in genes involved in DNA repair and
      apoptosis that was confirmed by TUNEL assay. Regarding the IVC related adverse
      phenotype transmitted to offspring, male glucose intolerance was shown only in F1
      and F2 male but not female offspring. The same occurred with male abnormalities
      in the organ size of the liver, which were transmitted to F1 and F2 males but not
      to F1 females; moreover, analysis of the F0, F1, and F2 males revealed greater
      coefficients of variance in body weight and glucose intolerance than the control
      group. Finally, we analyzed, through gene silencing, the effect of IVC on the
      mRNA expression at the blastocyst stage for 11 known gene expression modifiers of
      epigenetic reprogramming. Suboptimal IVC reduced the expression of Kap1, Sox2,
      Hdac1, Dnmt1, and Dnmt3a, suggesting a molecular epigenetic role for gene
      expression modifiers in the origin and transmission of these abnormal phenotypes.

PMID- 22649069
TI  - Parathyroid hormone-related protein stimulates plasma renin activity via its
      anorexic effects on sodium chloride intake.
AB  - Parathyroid hormone-related protein (PTHrP) increases renin release from isolated
      perfused kidneys and may act as an autacoid regulator of renin secretion, but its
      effects on renin in vivo are unknown. In vivo, PTHrP causes hypercalcemia and
      anorexia, which may affect renin. We hypothesized that chronically elevated PTHrP
      would increase plasma renin activity (PRA) indirectly via its anorexic effects,
      reducing sodium chloride (NaCl) intake and causing NaCl restriction. We infused
      male Sprague-Dawley rats with the vehicle (control) or 125 MUg PTHrP/day (PTHrP)
      via subcutaneous osmotic minipumps for 5 days. To replenish NaCl consumption, a
      third group of PTHrP-infused rats received 0.3% NaCl (PTHrP + NaCl) in their
      drinking water. PTHrP increased PRA from a median control value of 3.68 to 18.4
      ng Ang I.ml(-1).h(-1) (P < 0.05), whereas the median PTHrP + NaCl PRA value was
      normal (7.82 ng Ang I.ml(-1).h(-1), P < 0.05 vs. PTHrP). Plasma Ca(2+) (median
      control: 10.2 mg/dl; PTHrP: 13.7 mg/dl; PTHrP + NaCl: 14.1 mg/dl; P < 0.05) and
      PTHrP (median control: 0.03 ng/ml; PTHrP: 0.12 ng/ml; PTHrP + NaCl: 0.15 ng/ml; P
      < 0.05) were elevated in PTHrP- and PTHrP + NaCl-treated rats. Body weights and
      caloric consumption were lower in PTHrP- and PTHrP + NaCl-treated rats. NaCl
      consumption was lower in PTHrP-treated rats (mean Na(+): 28.5 +/- 4.1 mg/day;
      mean Cl(-): 47.8 mg/day) compared with controls (Na(+): 67.3 +/- 2.7 mg/day; Cl(
      ): 112.8 +/- 4.6 mg/day; P < 0.05). NaCl consumption was comparable with control
      in the PTHrP + NaCl group; 0.3% NaCl in the drinking water had no effect on PRA
      in normal rats. Thus, our data support the hypothesis that PTHrP increases PRA
      via its anorexic effects, reducing NaCl intake and causing NaCl restriction.

PMID- 22649071
TI  - Regulation of gap-junctional communication between cumulus cells during in vitro
      maturation in swine, a gap-FRAP study.
AB  - Intercellular gap-junctional communication (GJC) plays an important role in
      ovarian cell physiology. Closure of GJC has been proposed to be involved in
      oocyte maturation, particularly in the resumption of meiosis, both in vivo and in
      vitro, by controlling the flow of meiosis inhibitors, such as cAMP and cGMP.
      Understanding how GJC dynamics are regulated during in vitro maturation (IVM)
      could provide a powerful tool for controlling meiotic resumption and oocyte
      maturation in vitro. Since little is known about the GJC dynamic regulation
      between cumulus cells, we have developed an assay based on recovery of calcein
      fluorescence in photobleached cumulus cells, a gap-FRAP assay. The GJC profile
      has been characterized during the first hours of porcine IVM. We showed that
      equine chorionic gonadotropin (eCG) and epidermal growth factor (EGF) down
      regulated GJC effectiveness between cumulus cells. However, human chorionic
      gonadotropin was not down-regulating GJC effectiveness. We also showed that the
      GJC network expanded during this period and that this effect was not regulated by
      gonadotropins. Porcine follicular fluid present in the maturation medium also had
      an impact on GJC regulation, increasing GJC network establishment and the
      effectiveness of calcein transfer rate between cumulus cells. These results show
      that both eCG and EGF are regulating the decrease in GJC effectiveness after 4.5
      h of IVM, while the network extension is gonadotropin independent. Regulation of
      GJC between cumulus cells would then be specifically regulated during in vitro
      IVM.

PMID- 22649072
TI  - The pathophysiology of preeclampsia involves altered levels of angiogenic factors
      promoted by hypoxia and autoantibody-mediated mechanisms.
AB  - Pre-eclampsia is a syndrome characterized by inadequate placentation, which is
      due to deficient trophoblastic invasion of the uterine spiral arteries. This
      deficiency can lead to placental hypoxia, secretion of proinflammatory cytokines,
      and release of angiogenic and antiangiogenic factors. Hypoxic conditions in the
      placenta can promote oxidative stress and the production of angiogenic factors
      that are antagonized by soluble receptors, which are also elevated in this
      syndrome. In addition to these factors, the development of hypertension in women
      with pre-eclampsia may be associated with the renin-angiotensin system and
      endothelial dysfunction. The presence of antiangiotensin II type 1 receptor
      autoantibodies is relevant in pre-eclampsia because it has been related to the
      secretion of antiangiogenic factors through cytokine pathways, indicating that
      autoimmune mechanisms may participate in the pathophysiology of this syndrome.

PMID- 22649073
TI  - Follicle-stimulating hormone and luteinizing hormone mediate the androgenic
      pathway in Leydig cells of an evolutionary advanced teleost.
AB  - The endocrine pathways controlling vertebrate spermatogenesis are well
      established in mammals where the pituitary gonadotropins follicle-stimulating
      hormone (FSH) and luteinizing hormone (LH) exclusively activate the FSH receptor
      (FSHR) in Sertoli cells and the LH/choriogonadotropin receptor (LHCGR) in Leydig
      cells, respectively. In some teleosts, however, it has been shown that Lh can
      cross-activate the Fshra ortholog, and that Leydig cells coexpress the Lhcgrba
      and Fshra paralogs, thus mediating the androgenic function of Fsh in the testis.
      Here, we investigated whether these proposed mechanisms are conserved in an
      evolutionary advanced pleuronectiform teleost, the Senegalese sole (Solea
      senegalensis). Transactivation assays using sole Fshra- and Lhcgrba-expressing
      cells and homologous single-chain recombinant gonadotropins (rFsh and rLh) showed
      that rFsh exclusively activated Fshra, whereas rLh stimulated both Lhcgrba and
      Fshra. The latter cross-activation of Fshra by rLh occurred with an EC(50) 4-fold
      higher than for rFsh. Both recombinant gonadotropins elicited a significant
      androgen release response in vitro and in vivo, which was blocked by protein
      kinase A (PKA) and 3beta-hydroxysteroid dehydrogenase inhibitors, suggesting that
      activation of steroidogenesis through the cAMP/PKA pathway is the major route for
      both Lh- and Fsh-stimulated androgen secretion. Combined in situ hybridization
      and immunocytochemistry using cell-specific molecular markers and antibodies
      specifically raised against sole Fshra and Lhcgrba demonstrated that both
      receptors are expressed in Leydig cells, whereas Sertoli cells only express
      Fshra. These data suggest that Fsh-mediated androgen production through the
      activation of cognate receptors in Leydig cells is a conserved pathway in
      Senegalese sole.

PMID- 22649074
TI  - Overexpression of follistatin in the mouse epididymis disrupts fluid resorption
      and sperm transit in testicular excurrent ducts.
AB  - Activin is a well-established modulator of male and female reproduction that
      stimulates the synthesis and secretion of follicle-stimulating hormone.
      Nonpituitary effects of activin have also been reported, although the paracrine
      actions of this growth factor in several reproductive tissues are not well
      understood. To identify the paracrine functions of activin during mammary gland
      morphogenesis and tumor progression, we produced transgenic mice that overexpress
      follistatin (FST), an intrinsic inhibitor of activin, under control of the mouse
      mammary tumor virus (MMTV) promoter. Although the MMTV-Fst mice were constructed
      to assess the role of activin in females, expression of the transgene was also
      observed in the testes and epididymides of males. While all 17 transgenic founder
      males exhibited copulatory behavior and produced vaginal plugs in females, only
      one produced live offspring. In contrast, transgenic females were fertile,
      permitting expansion of transgenic mouse lines. Light and transmission electron
      microscopic examination of the transgenic testes and epididymides revealed
      impairment of fluid resorption and sperm transit in the efferent ducts and
      initial segment of the epididymis, as indicated by accumulation of fluid and
      sperm stasis. Consequently, a variety of degenerative lesions were observed in
      the seminiferous epithelium, such as vacuolation and early stages of
      mineralization and fibrosis. Sperm collected from the caudae epididymidis of MMTV
      Fst males had detached heads and were immotile. Together, these data reveal that
      activin signaling is essential for normal testicular excurrent duct function and
      that its blockade impairs fertility. These results also suggest that selective
      inhibitors of activin signaling may provide a useful approach for the development
      of male contraceptives without compromising androgen synthesis and actions.

PMID- 22649075
TI  - Slc2a8 deficiency in mice results in reproductive and growth impairments.
AB  - SLC2A8, also known as GLUT8, is a facilitative glucose transporter expressed in
      the testis, brain, liver, heart, uterus, ovary, and fat. In this study we
      examined the effect of Slc2a8 deficiency on mouse gamete, preimplantation embryo,
      and implantation phenotype, as well as postnatal growth and physiology. For this
      model, the transcriptional start site and exons 1-4 were targeted and a lack of
      protein expression was confirmed by Western immunoblot. Oocytes obtained from
      Slc2a8(-/-) mice demonstrated abnormal metabolism and ATP production. In
      addition, deletion of Slc2a8 resulted in impaired decidualization, a critical
      step in the differentiation of endometrial stromal cells (ESCs), necessary for
      implantation. This indicates a role for SLC2A8 in decidualization, which is
      supported by Slc2a8 mRNA expression in both mouse and human ESCs, which increases
      dramatically in response to hormonal changes occurring during the process of
      implantation. Ovarian transplantation studies confirm that lack of SLC2A8 affects
      both the embryo and the implantation processes. This phenotype leads to decreased
      litter size, and smaller pups at weaning that continue to display an abnormally
      small growth phenotype into adulthood. The Slc2a8 null mice display decreased
      body fat by magnetic resonance imaging, and, interestingly, they are resistant to
      a diet high in fat and carbohydrates.

PMID- 22649076
TI  - Nucleolar dominance of the Y chromosome in Drosophila melanogaster.
AB  - The rDNA genes are transcribed by RNA polymerase I to make structural RNAs for
      ribosomes. Hundreds of rDNA genes are typically arranged in an array that spans
      megabase pairs of DNA. These arrays are the major sites of transcription in
      growing cells, accounting for as much as 50% of RNA synthesis. The repetitive
      rDNA arrays are thought to use heterochromatic gene silencing as a mechanism for
      metabolic regulation, since repeated sequences nucleate heterochromatin formation
      in eukaryotes. Drosophila melanogaster carries an rDNA array on the X chromosome
      and on the Y chromosome, and genetic analysis has suggested that both are
      transcribed. However, using a chromatin-marking assay, we find that the entire X
      chromosome rDNA array is normally silenced in D. melanogaster males, while the Y
      chromosome rDNA array is dominant and expressed. This resembles "nucleolar
      dominance," a phenomenon that occurs in interspecific hybrids where an rDNA array
      from one parental species is silenced, and that from the other parent is
      preferentially transcribed. Interspecies nucleolar dominance is thought to result
      from incompatibilities between species-specific transcription factors and the
      rDNA promoters in the hybrid, but our results show that nucleolar dominance is a
      normal feature of rDNA regulation. Nucleolar dominance within D. melanogaster is
      only partially dependent on known components of heterochromatic gene silencing,
      implying that a distinctive chromatin regulatory system may act at rDNA genes.
      Finally, we isolate variant Y chromosomes that allow X chromosome array
      expression and suggest that the large-scale organization of rDNA arrays
      contribute to nucleolar dominance. This is the first example of allelic
      inactivation in D. melanogaster.

PMID- 22649077
TI  - Divergent functions through alternative splicing: the Drosophila CRMP gene in
      pyrimidine metabolism, brain, and behavior.
AB  - DHP and CRMP proteins comprise a family of structurally similar proteins that
      perform divergent functions, DHP in pyrimidine catabolism in most organisms and
      CRMP in neuronal dynamics in animals. In vertebrates, one DHP and five CRMP
      proteins are products of six genes; however, Drosophila melanogaster has a single
      CRMP gene that encodes one DHP and one CRMP protein through tissue-specific,
      alternative splicing of a pair of paralogous exons. The proteins derived from the
      fly gene are identical over 90% of their lengths, suggesting that unique, novel
      functions of these proteins derive from the segment corresponding to the
      paralogous exons. Functional homologies of the Drosophila and mammalian CRMP
      proteins are revealed by several types of evidence. Loss-of-function CRMP
      mutation modifies both Ras and Rac misexpression phenotypes during fly eye
      development in a manner that is consistent with the roles of CRMP in Ras and Rac
      signaling pathways in mammalian neurons. In both mice and flies, CRMP mutation
      impairs learning and memory. CRMP mutant flies are defective in circadian
      activity rhythm. Thus, DHP and CRMP proteins are derived by different processes
      in flies (tissue-specific, alternative splicing of paralogous exons of a single
      gene) and vertebrates (tissue-specific expression of different genes), indicating
      that diverse genetic mechanisms have mediated the evolution of this protein
      family in animals.

PMID- 22649078
TI  - Transvection is common throughout the Drosophila genome.
AB  - Higher-order genome organization plays an important role in transcriptional
      regulation. In Drosophila, somatic pairing of homologous chromosomes can lead to
      transvection, by which the regulatory region of a gene can influence
      transcription in trans. We observe transvection between transgenes inserted at
      commonly used phiC31 integration sites in the Drosophila genome. When two
      transgenes that carry endogenous regulatory elements driving the expression of
      either LexA or GAL4 are inserted at the same integration site and paired, the
      enhancer of one transgene can drive or repress expression of the paired
      transgene. These transvection effects depend on compatibility between regulatory
      elements and are often restricted to a subset of cell types within a given
      expression pattern. We further show that activated UAS transgenes can also drive
      transcription in trans. We discuss the implication of these findings for (1)
      understanding the molecular mechanisms that underlie transvection and (2) the
      design of experiments that utilize site-specific integration.

PMID- 22649080
TI  - Bypassing the Greatwall-Endosulfine pathway: plasticity of a pivotal cell-cycle
      regulatory module in Drosophila melanogaster and Caenorhabditis elegans.
AB  - In vertebrates, mitotic and meiotic M phase is facilitated by the kinase
      Greatwall (Gwl), which phosphorylates a conserved sequence in the effector
      Endosulfine (Endos). Phosphorylated Endos inactivates the phosphatase PP2A/B55 to
      stabilize M-phase-specific phosphorylations added to many proteins by cyclin
      dependent kinases (CDKs). We show here that this module functions essentially
      identically in Drosophila melanogaster and is necessary for proper mitotic and
      meiotic cell division in a wide variety of tissues. Despite the importance and
      evolutionary conservation of this pathway between insects and vertebrates, it can
      be bypassed in at least two situations. First, heterozygosity for loss-of
      function mutations of twins, which encodes the Drosophila B55 protein, suppresses
      the effects of endos or gwl mutations. Several types of cell division occur
      normally in twins heterozygotes in the complete absence of Endos or the near
      absence of Gwl. Second, this module is nonessential in the nematode Caenorhaditis
      elegans. The worm genome does not contain an obvious ortholog of gwl, although it
      encodes a single Endos protein with a surprisingly well-conserved Gwl target
      site. Deletion of this site from worm Endos has no obvious effects on cell
      divisions involved in viability or reproduction under normal laboratory
      conditions. In contrast to these situations, removal of one copy of twins does
      not completely bypass the requirement for endos or gwl for Drosophila female
      fertility, although reducing twins dosage reverses the meiotic maturation defects
      of hypomorphic gwl mutants. These results have interesting implications for the
      function and evolution of the mechanisms modulating removal of CDK-directed
      phosphorylations.

PMID- 22649081
TI  - SNP-Ratio Mapping (SRM): identifying lethal alleles and mutations in complex
      genetic backgrounds by next-generation sequencing.
AB  - We present a generally applicable method allowing rapid identification of causal
      alleles in mutagenized genomes by next-generation sequencing. Currently used
      approaches rely on recovering homozygotes or extensive backcrossing. In contrast,
      SNP-ratio mapping allows rapid cloning of lethal and/or poorly transmitted
      mutations and second-site modifiers, which are often in complex
      genetic/transgenic backgrounds.

PMID- 22649082
TI  - Robust estimation of local genetic ancestry in admixed populations using a
      nonparametric Bayesian approach.
AB  - We present a new haplotype-based approach for inferring local genetic ancestry of
      individuals in an admixed population. Most existing approaches for local ancestry
      estimation ignore the latent genetic relatedness between ancestral populations
      and treat them as independent. In this article, we exploit such information by
      building an inheritance model that describes both the ancestral populations and
      the admixed population jointly in a unified framework. Based on an assumption
      that the common hypothetical founder haplotypes give rise to both the ancestral
      and the admixed population haplotypes, we employ an infinite hidden Markov model
      to characterize each ancestral population and further extend it to generate the
      admixed population. Through an effective utilization of the population structural
      information under a principled nonparametric Bayesian framework, the resulting
      model is significantly less sensitive to the choice and the amount of training
      data for ancestral populations than state-of-the-art algorithms. We also improve
      the robustness under deviation from common modeling assumptions by incorporating
      population-specific scale parameters that allow variable recombination rates in
      different populations. Our method is applicable to an admixed population from an
      arbitrary number of ancestral populations and also performs competitively in
      terms of spurious ancestry proportions under a general multiway admixture
      assumption. We validate the proposed method by simulation under various admixing
      scenarios and present empirical analysis results from a worldwide-distributed
      dataset from the Human Genome Diversity Project.

PMID- 22649083
TI  - Comparing enhancer action in cis and in trans.
AB  - Studies from diverse systems have shown that distinct interchromosomal
      interactions are a central component of nuclear organization. In some cases,
      these interactions allow an enhancer to act in trans, modulating the expression
      of a gene encoded on a separate chromosome held in close proximity. Despite
      recent advances in uncovering such phenomena, our understanding of how a
      regulatory element acts on another chromosome remains incomplete. Here, we
      describe a transgenic approach to better understand enhancer action in trans in
      Drosophila melanogaster. Using phiC31-based recombinase-mediated cassette
      exchange (RMCE), we placed transgenes carrying combinations of the simple
      enhancer GMR, a minimal promoter, and different fluorescent reporters at
      equivalent positions on homologous chromosomes so that they would pair via the
      endogenous somatic pairing machinery of Drosophila. Our data demonstrate that the
      enhancer GMR is capable of activating a promoter in trans and does so in a
      variegated pattern, suggesting stochastic interactions between the enhancer and
      the promoter when they are carried on separate chromosomes. Furthermore, we
      quantitatively assessed the impact of two concurrent promoter targets in cis and
      in trans to GMR, demonstrating that each promoter is capable of competing for the
      enhancer's activity, with the presence of one negatively affecting expression
      from the other. Finally, the single-cell resolution afforded by our approach
      allowed us to show that promoters in cis and in trans to GMR can both be
      activated in the same nucleus, implying that a single enhancer can share its
      activity between multiple promoter targets carried on separate chromosomes.

PMID- 22649079
TI  - Global population genetic structure of Caenorhabditis remanei reveals incipient
      speciation.
AB  - Mating system transitions dramatically alter the evolutionary trajectories of
      genomes that can be revealed by contrasts of species with disparate modes of
      reproduction. For such transitions in Caenorhabditis nematodes, some major causes
      of genome variation in selfing species have been discerned. And yet, we have only
      limited understanding of species-wide population genetic processes for their
      outcrossing relatives, which represent the reproductive state of the progenitors
      of selfing species. Multilocus-multipopulation sequence polymorphism data provide
      a powerful means to uncover the historical demography and evolutionary processes
      that shape genomes. Here we survey nucleotide polymorphism across the X
      chromosome for three populations of the outcrossing nematode Caenorhabditis
      remanei and demonstrate its divergence from a fourth population describing a
      closely related new species from China, C. sp. 23. We find high genetic variation
      globally and within each local population sample. Despite geographic barriers and
      moderate genetic differentiation between Europe and North America, considerable
      gene flow connects C. remanei populations. We discovered C. sp. 23 while
      investigating C. remanei, observing strong genetic differentiation characteristic
      of reproductive isolation that was confirmed by substantial F2 hybrid breakdown
      in interspecific crosses. That C. sp. 23 represents a distinct biological species
      provides a cautionary example of how standard practice can fail for mating tests
      of species identity in this group. This species pair permits full application of
      divergence population genetic methods to obligately outcrossing species of
      Caenorhabditis and also presents a new focus for interrogation of the genetics
      and evolution of speciation with the Caenorhabditis model system.

PMID- 22649084
TI  - Fluctuations of fitness distributions and the rate of Muller's ratchet.
AB  - The accumulation of deleterious mutations is driven by rare fluctuations that
      lead to the loss of all mutation free individuals, a process known as Muller's
      ratchet. Even though Muller's ratchet is a paradigmatic process in population
      genetics, a quantitative understanding of its rate is still lacking. The
      difficulty lies in the nontrivial nature of fluctuations in the fitness
      distribution, which control the rate of extinction of the fittest genotype. We
      address this problem using the simple but classic model of mutation selection
      balance with deleterious mutations all having the same effect on fitness. We show
      analytically how fluctuations among the fittest individuals propagate to
      individuals of lower fitness and have dramatically amplified effects on the bulk
      of the population at a later time. If a reduction in the size of the fittest
      class reduces the mean fitness only after a delay, selection opposing this
      reduction is also delayed. This delayed restoring force speeds up Muller's
      ratchet. We show how the delayed response can be accounted for using a path
      integral formulation of the stochastic dynamics and provide an expression for the
      rate of the ratchet that is accurate across a broad range of parameters.

PMID- 22649086
TI  - Retinopathy of prematurity: are we missing any infant with retinopathy of
      prematurity?
AB  - AIMS: To evaluate incidence of retinopathy of prematurity (ROP) and validity of
      current ROP screening criteria adopted in the Armed Forces Hospitals. METHODS: A
      retrospective study of ROP indices was carried out in infants admitted to the
      neonatal intensive care unit in Khamis Mushait, Saudi Arabia, from January 2009
      to December 2011. All infants who had birth weight (BW) of 1500 g or less and/or
      gestational age (GA) of 32 weeks or less had their data reviewed for ROP
      diagnosis and related indices. Some heavier or older infants were also included
      in the study. RESULTS: 386 infants were screened and ROP was diagnosed in 90
      infants (23.31%). 25 infants (6.47%) had type 1 or worse ROP and were treated
      with cryopexy or laser. For patients having ROP, the mean GA was 27.8 +/- 2 weeks
      and mean BW was 961.8 +/- 237.4 g. Infants who needed treatment for ROP had a
      mean BW of 828.8 +/- 192.8 g and mean GA of 27 +/- 1.8 weeks. All infants who
      developed ROP fulfilled both or one criterion of ROP screening. No infant greater
      than 1350 g BW or more than 31 weeks GA was treated for ROP. CONCLUSIONS: Current
      ROP screening criteria of BW of 1500 g or less and/or GA of 32 weeks or less
      seems reasonable in our set up as no infant having ROP was missed by using these
      criteria. We do not recommend lowering or using only one index for ROP screening.

PMID- 22649087
TI  - Seeking validation.

PMID- 22649085
TI  - Analyses of dynein heavy chain mutations reveal complex interactions between
      dynein motor domains and cellular dynein functions.
AB  - Cytoplasmic dynein transports cargoes for a variety of crucial cellular
      functions. However, since dynein is essential in most eukaryotic organisms, the
      in-depth study of the cellular function of dynein via genetic analysis of dynein
      mutations has not been practical. Here, we identify and characterize 34 different
      dynein heavy chain mutations using a genetic screen of the ascomycete fungus
      Neurospora crassa, in which dynein is nonessential. Interestingly, our studies
      show that these mutations segregate into five different classes based on the in
      vivo localization of the mutated dynein motors. Furthermore, we have determined
      that the different classes of dynein mutations alter vesicle trafficking,
      microtubule organization, and nuclear distribution in distinct ways and require
      dynactin to different extents. In addition, biochemical analyses of dynein from
      one mutant strain show a strong correlation between its in vitro biochemical
      properties and the aberrant intracellular function of that altered dynein. When
      the mutations were mapped to the published dynein crystal structure, we found
      that the three-dimensional structural locations of the heavy chain mutations were
      linked to particular classes of altered dynein functions observed in cells.
      Together, our data indicate that the five classes of dynein mutations represent
      the entrapment of dynein at five separate points in the dynein mechanochemical
      and transport cycles. We have developed N. crassa as a model system where we can
      dissect the complexities of dynein structure, function, and interaction with
      other proteins with genetic, biochemical, and cell biological studies.

PMID- 22649088
TI  - Relief from within: a peptide therapy for fibrosis.
AB  - A modified, natural peptide derived from the antiangiogenic molecule endostatin
      has the potential to become a breakthrough therapy for organ fibrosis (Yamaguchi
      et al., this issue).

PMID- 22649089
TI  - Noninvasive identification and monitoring of cancer mutations by targeted deep
      sequencing of plasma DNA.
AB  - Plasma of cancer patients contains cell-free tumor DNA that carries information
      on tumor mutations and tumor burden. Individual mutations have been probed using
      allele-specific assays, but sequencing of entire genes to detect cancer mutations
      in circulating DNA has not been demonstrated. We developed a method for tagged
      amplicon deep sequencing (TAm-Seq) and screened 5995 genomic bases for low
      frequency mutations. Using this method, we identified cancer mutations present in
      circulating DNA at allele frequencies as low as 2%, with sensitivity and
      specificity of >97%. We identified mutations throughout the tumor suppressor gene
      TP53 in circulating DNA from 46 plasma samples of advanced ovarian cancer
      patients. We demonstrated use of TAm-Seq to noninvasively identify the origin of
      metastatic relapse in a patient with multiple primary tumors. In another case, we
      identified in plasma an EGFR mutation not found in an initial ovarian biopsy. We
      further used TAm-Seq to monitor tumor dynamics, and tracked 10 concomitant
      mutations in plasma of a metastatic breast cancer patient over 16 months. This
      low-cost, high-throughput method could facilitate analysis of circulating DNA as
      a noninvasive "liquid biopsy" for personalized cancer genomics.

PMID- 22649090
TI  - SIV replication in the infected rhesus macaque is limited by the size of the
      preexisting TH17 cell compartment.
AB  - The mechanisms by which some HIV-infected subjects resist disease progression,
      whereas others progress rapidly, are incompletely understood. Viral and host
      genetic factors, such as nef deletions and major histocompatibility complex
      alleles, explain a portion of the observed variability. However, it has been
      difficult to identify host immune functions that may be present before infection
      and that allow resistance to lentiviral disease progression. Here, we show that
      simian immunodeficiency virus replication in the infected rhesus macaque is
      limited by the size of the preexisting T helper 17 (T(H)17) cell compartment:
      Animals with a high representation of such cells in blood and intestinal tissue
      before infection experienced peak and set-point viral loads about one log unit
      lower than those with a lower representation of T(H)17 cells. Reciprocally,
      treatment of macaques with interleukin-2 and granulocyte colony-stimulating
      factor before infection led to depletion of T(H)17 cells, reduction of the ratio
      between T(H)17 cells and CD3(+)CD4(+)CD25(+)CD127(low) regulatory T cells, and
      higher viral loads for 6 months after infection. These results demonstrate that
      the composition of the host immune system before infection has an influence on
      the course of disease after infection. Furthermore, to the extent that this
      influence shapes and interacts with T cell-mediated responses to virus, our
      findings provide a new framework for understanding interindividual variation in
      responses to therapies and vaccines against HIV.

PMID- 22649091
TI  - Kinase-impaired BRAF mutations in lung cancer confer sensitivity to dasatinib.
AB  - During a clinical trial of the tyrosine kinase inhibitor dasatinib for advanced
      non-small cell lung cancer (NSCLC), one patient responded dramatically and
      remains cancer-free 4 years later. A comprehensive analysis of his tumor revealed
      a previously undescribed, kinase-inactivating BRAF mutation ((Y472C)BRAF); no
      inactivating BRAF mutations were found in the nonresponding tumors taken from
      other patients. Cells transfected with (Y472C)BRAF exhibited CRAF, MEK (mitogen
      activated or extracellular signal-regulated protein kinase kinase), and ERK
      (extracellular signal-regulated kinase) activation-characteristics identical to
      signaling changes that occur with previously known kinase-inactivating BRAF
      mutants. Dasatinib selectively induced senescence in NSCLC cells with
      inactivating BRAF mutations. Transfection of other NSCLC cells with these BRAF
      mutations also increased these cells' dasatinib sensitivity, whereas transfection
      with an activating BRAF mutation led to their increased dasatinib resistance. The
      sensitivity induced by (Y472C)BRAF was reversed by the introduction of a BRAF
      mutation that impairs RAF dimerization. Dasatinib inhibited CRAF modestly, but
      concurrently induced RAF dimerization, resulting in ERK activation in NSCLC cells
      with kinase-inactivating BRAF mutations. The sensitivity of NSCLC with kinase
      impaired BRAF to dasatinib suggested synthetic lethality of BRAF and an unknown
      dasatinib target. Inhibiting BRAF in NSCLC cells expressing wild-type BRAF
      likewise enhanced these cells' dasatinib sensitivity. Thus, the patient's BRAF
      mutation was likely responsible for his tumor's marked response to dasatinib,
      suggesting that tumors bearing kinase-impaired BRAF mutations may be exquisitely
      sensitive to dasatinib. Moreover, the potential synthetic lethality of
      combination therapy including dasatinib and BRAF inhibitors may lead to
      additional therapeutic options against cancers with wild-type BRAF.

PMID- 22649092
TI  - A peptide derived from endostatin ameliorates organ fibrosis.
AB  - Fibroproliferative disorders such as idiopathic pulmonary fibrosis and systemic
      sclerosis have no effective therapies and result in significant morbidity and
      mortality due to progressive organ fibrosis. We examined the effect of peptides
      derived from endostatin on existing fibrosis and fibrosis triggered by two potent
      mediators, transforming growth factor-beta (TGF-beta) and bleomycin, in human and
      mouse tissues in vitro, ex vivo, and in vivo. We identified one peptide, E4, with
      potent antifibrotic activity. E4 prevented TGF-beta-induced dermal fibrosis in
      vivo in a mouse model, ex vivo in human skin, and in bleomycin-induced dermal and
      pulmonary fibrosis in vivo, demonstrating that E4 exerts potent antifibrotic
      effects. In addition, E4 significantly reduced existing fibrosis in these
      preclinical models. E4 amelioration of fibrosis was accompanied by reduced cell
      apoptosis and lower levels of lysyl oxidase, an enzyme that cross-links collagen,
      and Egr-1 (early growth response gene-1), a transcription factor that mediates
      the effects of several fibrotic triggers. Our findings identify E4 as a peptide
      with potent antifibrotic activity and a possible therapeutic agent for organ
      fibrosis.

PMID- 22649093
TI  - Very late bare metal stent thrombosis due to neoatherosclerotic plaque rupture:
      an optical coherence tomography finding.

PMID- 22649094
TI  - A comparison of ECG scores for area at risk.

PMID- 22649096
TI  - Focus issue: signaling architecture from domains to complexes.
AB  - Science Signaling concludes a series on structural biology, which has focused on
      the use of structural approaches to understand signal transduction. Articles in
      this issue highlight the importance of the helical domain in Galpha proteins,
      discuss how linear peptide motifs are recognized by a protein domain, and
      describe the assembly of macromolecular complexes upon activation of Toll-like
      and interleukin-1 receptors.

PMID- 22649095
TI  - Advances in the hospital management of patients following an out of hospital
      cardiac arrest.
AB  - The outcome for patients after an out-of-hospital cardiac arrest (OHCA) has been
      poor over many decades and single interventions have mostly resulted in
      disappointing results. More recently, some regions have observed better outcomes
      after redesigning their cardiac arrest pathways. Optimised resuscitation and
      prehospital care is absolutely key, but in-hospital care appears to be at least
      as important. OHCA treatment requires a multidisciplinary approach, comparable to
      trauma care; the development of cardiac arrest pathways and cardiac arrest
      centres may dramatically improve patient care and outcomes. Besides emergency
      medicine physicians, intensivists and neurologists, cardiologists are playing an
      increasingly crucial role in the post-resuscitation management, especially by
      optimising cardiac output and undertaking urgent coronary
      angiography/intervention.

PMID- 22649097
TI  - Sequence-specific recognition of a PxLPxI/L motif by an ankyrin repeat tumbler
      lock.
AB  - Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane
      receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5. We
      report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory
      factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L
      motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin,
      and regulatory factor X, 5 (RFX5). Crystal structures of the ankyrin repeat
      domain of ANKRA2 in complex with its binding peptides revealed that each of the
      middle three ankyrin repeats of ANKRA2 recognizes a residue from the PxLPxI/L
      motif in a tumbler-lock binding mode, with ANKRA2 acting as the lock and the
      linear binding motif serving as the key. Structural analysis showed that three
      disease-causing mutations in RFXANK affect residues that are critical for binding
      to RFX5. These results suggest a fundamental principle of longitudinal
      recognition of linear sequences by a repeat-type domain. In addition,
      phosphorylation of serine 350, a residue embedded within the PxLPxI/L motif of
      HDAC4, impaired the binding of ANKRA2 but generated a high-affinity docking site
      for 14-3-3 proteins, which may help sequester this HDAC in the cytoplasm. Thus,
      the binding preference of the PxLPxI/L motif is signal-dependent. Furthermore,
      proteome-wide screening suggested that a similar phosphorylation-dependent switch
      may operate in other pathways. Together, our findings uncover a previously
      uncharacterized sequence- and signal-dependent peptide recognition mode for a
      repeat-type protein domain.

PMID- 22649098
TI  - Signal activation and inactivation by the Galpha helical domain: a long-neglected
      partner in G protein signaling.
AB  - Heterotrimeric guanine nucleotide-binding proteins (G proteins) are positioned at
      the top of many signal transduction pathways. The G protein alpha subunit is
      composed of two domains, one that resembles Ras and another that is composed
      entirely of alpha helices. Historically most attention has focused on the Ras
      like domain, but emerging evidence reveals that the helical domain is an active
      participant in G protein signaling.

PMID- 22649099
TI  - Structural insights into the assembly of large oligomeric signalosomes in the
      Toll-like receptor-interleukin-1 receptor superfamily.
AB  - The Toll-like receptor (TLR)-interleukin 1 receptor (IL-1R) superfamily plays
      fundamentally important roles in innate immune and inflammatory responses.
      Structural studies have begun to show that upon ligand stimulation, TLRs and IL
      1Rs assemble large oligomeric intracellular signaling complexes, or
      "signalosomes," to induce the activation of kinases and E3 ubiquitin ligases,
      leading eventually to the activation of the transcription factors that are
      responsible for the expression of genes whose products mediate immune and
      inflammatory responses. The different scaffolds identified by these structural
      studies provide a molecular foundation for understanding the formation of
      microscopically visible signaling clusters that have long been known to cell
      biologists. Here, we illustrate the potential mechanisms of step-by-step assembly
      from the membrane-proximal interactions to the more downstream events. Formation
      of large oligomeric signalosomes may help to establish a digital threshold
      response in TLR and IL-1R signaling.

PMID- 22649101
TI  - Essential role of TAK1 in regulating mantle cell lymphoma survival.
AB  - TGF-beta-activated kinase 1 (TAK1), a member of the MAPK kinase family, plays a
      key role in B-cell growth and development. In the present study, we examined the
      potential role of TAK1 as a therapeutic target for lymphoma. Here, we show that
      the active phosphorylated form of TAK1 is abundantly expressed in a panel of
      lymphoma cell lines, including mantle cell, anaplastic large cell, and Hodgkin
      lymphoma cell lines. Silencing TAK1 expression via the use of siRNA inhibited the
      activation of NF-kappaB and p38 and induced apoptosis in lymphoma cell lines.
      Moreover, submicromolar concentrations of AZ-TAK1, a novel ATP-competitive small
      molecule inhibitor of TAK1, dephosphorylated TAK1, p38, and IkappaB-alpha in
      lymphoma cell lines. These molecular events were associated with the release of
      cytochrome c into the cytosol, down-regulation of X-linked inhibitor of
      apoptosis, activation of caspase 9, and induction of apoptosis. We also
      demonstrate that primary lymphoma cells express TAK1 and pTAK1 and were sensitive
      to AZ-TAK1-mediated cell death. Collectively, our data demonstrate an essential
      role for TAK1 in regulating critical survival mechanisms in lymphoma and suggest
      that it may serve as a therapeutic target.

PMID- 22649103
TI  - IgG opsonization of bacteria promotes Th17 responses via synergy between TLRs and
      FcgammaRIIa in human dendritic cells.
AB  - Dendritic cells (DCs) are essential in inducing adaptive immune responses against
      bacteria by expressing cytokines that skew T-cell responses toward protective
      Th17 cells. Although it is widely recognized that induction of these cytokines by
      DCs involves activation of multiple receptors, it is still incompletely
      characterized which combination of receptors specifically skews Th17-cell
      responses. Here we have identified a novel role for FcgammaRIIa in promoting
      human Th17 cells. Activation of DCs by bacteria opsonized by serum IgG strongly
      promoted Th17 responses, which was FcgammaRIIa-dependent and coincided with
      enhanced production of selected cytokines by DCs, including Th17-promoting IL
      1beta and IL-23. Notably, FcgammaRIIa stimulation on DCs did not induce cytokine
      production when stimulated individually, but selectively amplified cytokine
      responses through synergy with TLR2, 4, or 5. Importantly, this synergy is
      mediated at 2 different levels. First, TLR-FcgammaRIIa costimulation strongly
      increased transcription of pro-IL-1beta and IL-23p19. Second, FcgammaRIIa
      triggering induced activation of caspase-1, which cleaves pro-IL-1beta into its
      bioactive form and thereby enhanced IL-1beta secretion. Taken together, these
      data identified cross-talk between TLRs and FcgammaRIIa as a novel mechanism by
      which DCs promote protective effector Th17-cell responses against bacteria.

PMID- 22649104
TI  - How I treat prolymphocytic leukemia.
AB  - T- and B-cell subtypes of prolymphocytic leukemia (PLL) are rare, aggressive
      lymphoid malignancies with characteristic morphologic, immunophenotypic,
      cytogenetic, and molecular features. Recent studies have highlighted the role of
      specific oncogenes, such as TCL-1, MTCP-1, and ATM in the case of T-cell and TP53
      mutations in the case of B-cell prolymphocytic leukemia. Despite the advances in
      the understanding of the biology of these conditions, the prognosis for these
      patients remains poor with short survival and no curative therapy. The advent of
      monoclonal antibodies has improved treatment options. Currently, the best
      treatment for T-PLL is intravenous alemtuzumab, which has resulted in very high
      response rates of more than 90% when given as first-line treatment and a
      significant improvement in survival. Consolidation of remissions with autologous
      or allogeneic stem cell transplantation further prolongs survival, and the latter
      may offer potential cure. In B-PLL, rituximab-based combination chemo
      immunotherapy is effective in fitter patients. TP53 abnormalities are common and,
      as for chronic lymphocytic leukemia, these patients should be managed using an
      alemtuzumab-based therapy. The role of allogeneic transplant with
      nonmyeloablative conditioning needs to be explored further in both T- and B-cell
      PLL to broaden the patient eligibility for what may be a curative treatment.

PMID- 22649102
TI  - CDP-diacylglycerol synthetase-controlled phosphoinositide availability limits
      VEGFA signaling and vascular morphogenesis.
AB  - Understanding the mechanisms that regulate angiogenesis and translating these
      into effective therapies are of enormous scientific and clinical interests. In
      this report, we demonstrate the central role of CDP-diacylglycerol synthetase
      (CDS) in the regulation of VEGFA signaling and angiogenesis. CDS activity
      maintains phosphoinositide 4,5 bisphosphate (PIP2) availability through
      resynthesis of phosphoinositides, whereas VEGFA, mainly through phospholipase
      Cgamma1, consumes PIP2 for signal transduction. Loss of CDS2, 1 of 2 vertebrate
      CDS enzymes, results in vascular-specific defects in zebrafish in vivo and
      failure of VEGFA-induced angiogenesis in endothelial cells in vitro. Absence of
      CDS2 also results in reduced arterial differentiation and reduced angiogenic
      signaling. CDS2 deficit-caused phenotypes can be successfully rescued by
      artificial elevation of PIP2 levels, and excess PIP2 or increased CDS2 activity
      can promote excess angiogenesis. These results suggest that availability of CDS
      controlled resynthesis of phosphoinositides is essential for angiogenesis.

PMID- 22649106
TI  - GATA2 zinc finger 1 mutations associated with biallelic CEBPA mutations define a
      unique genetic entity of acute myeloid leukemia.
AB  - Cytogenetically normal acute myeloid leukemia (CN-AML) with biallelic CEBPA gene
      mutations (biCEPBA) represents a distinct disease entity with a favorable
      clinical outcome. So far, it is not known whether other genetic alterations
      cooperate with biCEBPA mutations during leukemogenesis. To identify additional
      mutations, we performed whole exome sequencing of 5 biCEBPA patients and detected
      somatic GATA2 zinc finger 1 (ZF1) mutations in 2 of 5 cases. Both GATA2 and CEBPA
      are transcription factors crucial for hematopoietic development. Inherited or
      acquired mutations in both genes have been associated with leukemogenesis.
      Further mutational screening detected novel GATA2 ZF1 mutations in 13 of 33
      biCEBPA-positive CN-AML patients (13/33, 39.4%). No GATA2 mutations were found in
      38 CN-AML patients with a monoallelic CEBPA mutation and in 89 CN-AML patients
      with wild-type CEBPA status. The presence of additional GATA2 mutations (n=10)
      did not significantly influence the clinical outcome of 26 biCEBPA-positive
      patients. In reporter gene assays, all tested GATA2 ZF1 mutants showed reduced
      capacity to enhance CEBPA-mediated activation of transcription, suggesting that
      the GATA2 ZF1 mutations may collaborate with biCEPBA mutations to deregulate
      target genes during malignant transformation. We thus provide evidence for a
      genetically distinct subgroup of CN-AML. The German AML cooperative group trials
      1999 and 2008 are registered with the identifiers NCT00266136 and NCT01382147 at
      www.clinicaltrials.gov.

PMID- 22649105
TI  - HES1 opposes a PTEN-dependent check on survival, differentiation, and
      proliferation of TCRbeta-selected mouse thymocytes.
AB  - The developmental progression of immature thymocytes requires cooperative input
      from several pathways, with Notch signals playing an indispensable role at the T
      cell receptor (TCR)-beta selection checkpoint. Notch signals affect the
      activation of the PI3K/Akt pathway, which is required for pTalpha/TCRbeta (pre
      TCR)-induced survival, differentiation, and proliferation of developing alphabeta
      lineage thymocytes. However, the molecular players responsible for the
      interaction between the Notch and PI3K pathways at this critical developmental
      stage are unknown. Here, we show that Notch induction of Hes1 is necessary to
      repress the PI3K/Akt pathway inhibitor, PTEN (phosphatase and tensin homolog),
      which in turn facilitates pre-TCR-induced differentiation. In support of this
      mechanism, deletion or down-regulation of Pten overcomes the Notch signaling
      requirement for survival and differentiation during beta-selection. In addition,
      c-Myc is a critical target of Notch at this stage, as c-Myc expression overcomes
      the Notch signaling requirement for proliferation during beta-selection.
      Collectively, our results point to HES1, via repression of PTEN, and c-Myc as
      critical mediators of Notch function at the beta-selection checkpoint.

PMID- 22649107
TI  - Monoclonal antibodies against receptor-induced binding sites detect cell-bound
      plasminogen in blood.
AB  - Binding of Glu-plasminogen (the native, circulating form of the zymogen) to cells
      results in enhancement of its activation. Cell-associated plasmin proteolytic
      activity is a key component of physiologic and pathologic processes requiring
      extracellular matrix degradation. Recently, we developed antiplasminogen mAbs
      that recognize receptor-induced binding sites (RIBS) in Glu-plasminogen and,
      therefore, preferentially react with cell-associated Glu-plasminogen in the
      presence of soluble Glu-plasminogen. Here we have used FACS with a representative
      antiplasminogen receptor-induced binding site mAb, mAb49, to examine whether
      plasminogen associates with peripheral blood cells in blood. Plasminogen binding
      to neutrophils, monocytes, B-lymphocytes, T-lymphocytes, and platelets was
      clearly detected. Treatment of whole blood with lipopolysaccharide or 12-0
      tetradecanoylphorbol-13-acetate up-regulated plasminogen binding to neutrophils
      and in vivo treatment with all-trans retinoic acid decreased plasminogen binding
      to acute promyelocytic leukemia blasts. Our results demonstrate that mAb49 can be
      used to monitor cell-bound plasminogen in blood under both normal and pathologic
      conditions.

PMID- 22649108
TI  - Residual disease detected by multidimensional flow cytometry signifies high
      relapse risk in patients with de novo acute myeloid leukemia: a report from
      Children's Oncology Group.
AB  - Early response to induction chemotherapy is a predictor of outcome in acute
      myeloid leukemia (AML). We determined the prevalence and significance of
      postinduction residual disease (RD) by multidimensional flow cytometry (MDF) in
      children treated on Children's Oncology Group AML protocol AAML03P1.
      Postinduction marrow specimens at the end of induction (EOI) 1 or 2 or at the end
      of therapy from 249 patients were prospectively evaluated by MDF for RD, and
      presence of RD was correlated with disease characteristics and clinical outcome.
      Of the 188 patients in morphologic complete remission at EOI1, 46 (24%) had MDF
      detectable disease. Those with and without RD at the EOI1 had a 3-year relapse
      risk of 60% and 29%, respectively (P < .001); the corresponding relapse-free
      survival was 30% and 65% (P < .001). Presence of RD at the EOI2 and end of
      therapy was similarly predictive of poor outcome. RD was detected in 28% of
      standard-risk patients in complete remission and was highly associated with poor
      relapse-free survival (P = .008). In a multivariate analysis, including
      cytogenetic and molecular risk factors, RD was an independent predictor of
      relapse (P < .001). MDF identifies patients at risk of relapse and poor outcome
      and can be incorporated into clinical trials for risk-based therapy allocation.
      This study was registered at www.clinicaltrials.gov as NCT00070174.

PMID- 22649109
TI  - Impact of smoking and smoking cessation on arterial stiffness in healthy
      participants.
AB  - Smoking is associated with increased arterial stiffness. However, the impact of
      smoking cessation on arterial stiffness remains unknown. We investigated the
      effect of smoking cessation on arterial stiffness. Healthy participants (n = 209)
      were divided into nonsmoking (NSm, n = 96), quit smoking (QSm, n = 61), and
      maintained smoking groups (MSm, n = 52). Arterial stiffness indexes (ankle
      brachial index [ABI] and brachial-ankle pulse wave velocity [baPWV]) were
      assessed at baseline, and after 6 and 12 months. Baseline, arterial stiffness was
      significantly higher in the MSm and QSm groups than in the NSm group (P < .001).
      In the QSm group, there was significant difference in ABI between baseline and 12
      months (P = .03). No significant differences were shown in baPWV. Both ABI and
      baPWV were similar between QSm and MSm group at 12 months. However, there was
      significant difference between QSm and NSm groups (P < .001). This study shows
      that 12 months of smoking cessation is associated with improved arterial
      stiffness.

PMID- 22649110
TI  - Association between epicardial fat thickness and weight homeostasis hormones in
      patients with noncachectic heart failure.
AB  - The relationship between echocardiographically measured epicardial fat thickness
      (EFT) and plasma concentrations of leptin, ghrelin, and adiponectin has not been
      evaluated in patients with noncachectic heart failure (HF). Patients with
      noncachectic HF and age- and sex-matched controls did not differ significantly in
      EFT, whereas EFT values showed significant positive correlation with body mass
      index (BMI) in both groups and were negatively related with brain natriuretic
      peptide and positively with log leptin values in the HF group. In the control
      group, a positive correlation with high-sensitivity C-reactive protein (hsCRP)
      and a negative correlation with log ghrelin were found. In multivariable
      analysis, log leptin was a significant predictor of EFT in patients with HF, but
      this effect was not retained after adjusting for BMI. In contrast, log ghrelin
      and hsCRP were significant predictors of EFT in controls even after adjusting for
      BMI.

PMID- 22649111
TI  - Pressure indices in peripheral arterial disease assessed by infrared
      photosensors.
AB  - Ankle-brachial index (ABI) assessment by Doppler is operator dependent and
      limited in calcified arteries. For the detection of peripheral arterial disease
      (PAD), we evaluated ABI and toe-finger (ToFi) pressures by infrared (IR) sensors
      at the digits and compared with standard Doppler (Doppler-ABI) in 100 patients
      with PAD and in 15 controls. Pressure indices were obtained in 86% for Doppler
      ABI, 82% for IR-ABI, and 94% for IR-ToFi (P < .01). According to Bland-Altmann
      analysis, IR-ABI and Doppler-ABI are exchangeable (limits of agreement [loa] 
      0.30; 0.30, bias -0.003, 95% confidence interval [CI] -0.02; 0.02), whereas IR
      ToFi was not (loa -0.23; 0.61, bias of 0.2, 95% CI 0.16; 0.23). The IR-ToFi
      revealed the best inter- and intrarater agreement (0.92/0.98) followed by IR-ABI
      (0.74/0.98) and Doppler-ABI (0.66/0.89). Ankle-brachial arterial pressure index
      can be assessed by IR photosensors. Although toe-finger index is not exchangeable
      with standard Doppler, it will need further exploration to define its value for
      the diagnosis of PAD due to its excellent inter- and intrarater agreement.

PMID- 22649112
TI  - Serum uric acid levels are associated with atrial fibrillation in patients with
      ischemic heart failure.
AB  - We evaluated the association between serum uric acid (SUA) and atrial
      fibrillation (AF) in patients with chronic heart failure (HF). Totally, 363
      patients with chronic HF were included in the study. Of all, 78 patients had AF
      and 285 patients were in normal sinus rhythm. Serum uric acid was significantly
      increased in patients with AF compared with patients in normal sinus rhythm (P <
      .05). Comparing patients with AF and normal sinus rhythm, we found that age was
      significantly higher in patients group with AF. Echocardiographic parameters
      including ejection fraction, left atrial diameter, left ventricle end-diastolic
      diameter, and left ventricle end-diastolic volume were also significantly higher
      in patients with AF compared with patients in normal sinus rhythm. We have shown
      that patients with AF have significantly higher SUA and this was independently
      associated with AF in patients with ischemic HF.

PMID- 22649113
TI  - Wishful information preference: positive fantasies mimic the effects of
      intentions.
AB  - When pursuing set goals or intentions, people prefer to acquire information about
      the pros rather than the cons of their goal pursuit. Little is known about
      information preferences at earlier stages, when people are not yet serious about
      pursuing a given future. In the present three studies, positive fantasies that
      depicted an idealized desired future--compared with fantasies that questioned
      whether the future would be so ideal--created a preference for pros over cons,
      just like set goals or intentions have been shown to do. Positive fantasies
      created a stronger preference for pros versus cons when people were not serious
      about pursuing an imagined future or had just foregone an opportunity to do so.
      Results suggest that before people are engaged in serious pursuits, positive
      fantasies spur the selective acquisition of pro information, which may lead to
      poor decisions even if the acquired information is carefully deliberated on
      later.

PMID- 22649114
TI  - Biases in affective forecasting and recall in individuals with depression and
      anxiety symptoms.
AB  - The authors used experience sampling to investigate biases in affective
      forecasting and recall in individuals with varying levels of depression and
      anxiety symptoms. Participants who were higher in depression symptoms
      demonstrated stronger (more pessimistic) negative mood prediction biases,
      marginally stronger negative mood recall biases, and weaker (less optimistic)
      positive mood prediction and recall biases. Participants who were higher in
      anxiety symptoms demonstrated stronger negative mood prediction biases, but
      positive mood prediction biases that were on par with those who were lower in
      anxiety. Anxiety symptoms were not associated with mood recall biases. Neither
      depression symptoms nor anxiety symptoms were associated with bias in event
      prediction. Their findings fit well with the tripartite model of depression and
      anxiety. Results are also consistent with the conceptualization of anxiety as a
      "forward-looking" disorder, and with theories that emphasize the importance of
      pessimism and general negative information processing in depressive functioning.

PMID- 22649115
TI  - The danger in deception: oedipal betrayal and the assault on truth.
AB  - Certain potential precursors to heterosexual women's experience of partner
      infidelity are explored as these dynamics unfold within the oedipal crisis-the
      "betrayal" by the oedipal objects. As each child moves into the oedipal phase, he
      or she comes to recognize not only desire for the mother, but the mother's desire
      for the father. A doubling of this experience of "deception," encountered first
      in relation to the mother, and then repeated with the father, may be especially
      pronounced for a girl, as she is likely to inhabit more fully her bisexual
      potential in negotiating the expected shift of object choice from mother to
      father. "Deceived" by her primary maternal oedipal object, a girl sets forth
      toward her paternal oedipal object with "fidelity" already an issue, and with
      faith in her mind's ability to determine reality already shaken. Undermined trust
      in self and other is the context in which she begins the oedipal relation to her
      heterosexual object. This path is quite distinct from that traveled by the
      heterosexual boy. Clinical material illustrates the assault on one's mind, on
      one's confidence to determine what is true, that is a central aspect of both
      oedipal and adult betrayal.

PMID- 22649116
TI  - Otitis externa.

PMID- 22649117
TI  - Waiting times in English emergency departments reach eight year high.

PMID- 22649118
TI  - The new NHS information strategy.

PMID- 22649119
TI  - High Court quashes anaesthetist's 12 month suspension by GMC.

PMID- 22649121
TI  - The role of progesterone and its receptor on cyclin G1 expression in endometrial
      carcinoma cells.
AB  - Cyclin G1 protein is expressed in normal endometrial epithelial cells in a
      progesterone-dependent manner. It is an important mediator of the inhibiting
      effect of progesterone on cell proliferation. Moreover, the expression of cyclin
      G1 is also found to be decreased in human endometrial carcinoma cells (ECCs). To
      study the mechanism of decrease in the expression levels of cyclin G1, 3 ECC cell
      lines, Ishikawa, HEC-1-B, and KLE cells were treated with progesterone (P(4)).
      The KLE cells, in which progesterone receptor (PR) expression was absent, were
      transfected with PR-expressing plasmid before treatment with P(4). The results
      showed that cyclin G1 expression increased in Ishikawa and HEC-1-B cells after
      treatment with P(4), additionally the cell proliferation was suppressed but not
      in KLE cells. When the PR-expressing plasmid was transfected into KLE cells, the
      effect of P(4) was restored. Our data suggest that the deficiency of progesterone
      and its receptors is an important cause of the decreased expression of cyclin G1
      in endometrial carcinoma, which may account for carcinogenesis and development of
      endometrial carcinomas.

PMID- 22649122
TI  - The electrical activities of the uterus during pregnancy.
AB  - In contrast to the current state of knowledge of cardiac and of gastrointestinal
      electrophysiology, our current knowledge of the physiology of the uterus during
      pregnancy is still very rudimentary. Despite seminal work performed in the past
      decades, there are still significant areas that we know little about. In this
      review, some of these areas are explored. For example, although many studies have
      tried to find the site of the uterus pacemaker, such a site has not yet been
      found and its mechanism and location remain, to date, a mystery. Similarly, there
      is much confusion as to the mechanism of propagation of the electrical impulse.
      Although the existence of gap junctions, connecting neighboring myometrial cells
      to each other, have been known since 1977, alternative or additional mechanisms
      are being suggested such as the potential existence of a network of interstitial
      cells, similar to the one that is functioning in the gut, or the involvement of
      stretch receptors to synchronize activity and contraction. In recent years, high
      resolution studies have been introduced enabling detailed analysis of the
      location and spatial patterns of propagation. This work is being developed at the
      in-vitro level in isolated tissues, in the whole organ and in several animal
      species. Most recently, a surge in new technology enabling high fidelity and high
      resolution recording from the human uterus through the abdominal wall are being
      explored which could ultimately lead to new diagnostic tools and a clearer
      understanding of the physiology of pregnancies and (premature) labor.

PMID- 22649120
TI  - DigiFab interacts with endogenous cardiotonic steroids and reverses preeclampsia
      induced Na/K-ATPase inhibition.
AB  - Elevated levels of endogenous Na/K-ATPase (NKA) inhibitors, cardiotonic steroids
      (CTSs) including marinobufagenin (MBG), contribute to pathogenesis of
      preeclampsia (PE) and represent a target for immunoneutralization by Digibind
      (Ovine Digoxin Immune Antibody, Glaxo-Smith Kline). Because Digibind is no longer
      commercially available, we studied whether DigiFab (BTG International Ltd, UK)
      can substitute Digibind for immunoneutralization of CTS in patients with PE. We
      compared DigiFab, Digibind, and anti-MBG monoclonal antibody (mAb) with respect
      to their ability to interact with CTS in PE plasma and to restore NKA activity in
      erythrocytes from patients with PE. Using immunoassays based on DigiFab,
      Digibind, and anti-MBG mAb, we studied the elution profile of CTS following high
      performance liquid chromatography (HPLC) fractionation of PE plasma. Totally, 7
      patients with mild PE (28 +/- 2 years; gestational age, 39 +/- 0.5 weeks; blood
      pressure 156 +/- 5/94 +/- 2 mm Hg) and 6 normotensive pregnant participants (28
      +/- 1 years; gestational age, 39 +/- 0.4 weeks; blood pressure 111 +/- 2/73 +/- 2
      mm Hg) were enrolled. Preeclampsia was associated with a substantial inhibition
      of erythrocyte NKA (1.47 +/- 0.17 vs 2.65 +/- 0.16 umol Pi/mL per h in control
      group, P < .001). Ex vivo, at 10 ug/mL concentration, which is consistent with
      the clinical dosing of Digibind administered previously in PE, DigiFab and
      Digibind as well as anti-MBG mAb (0.5 ug/mL) restored erythrocyte NKA activity.
      Following HPLC fractionation of pooled PE and control plasma, PE-associated
      increase in CTS material was detected by Digibind (176 vs 75 pmoles), DigiFab
      (221 vs 70 pmoles), and anti-MBG mAb (1056 vs 421 pmoles). Therefore, because
      DigiFab interacts with CTS from PE plasma and reverses PE-induced NKA inhibition,
      it can substitute Digibind for immunoneutralization of CTS in patients with PE.

PMID- 22649123
TI  - The combined use of aspirin, a statin, and blood pressure-lowering agents
      (polypill components) in clinical practice in patients with vascular diseases or
      type 2 diabetes mellitus.
AB  - AIM: Based on guidelines, patients with established cardiovascular disease are
      likely to already receive a combination of aspirin, a statin, and blood pressure
      (BP)-lowering agents. Combining these pharmacological agents into a
      cardiovascular polypill could be considered in these patients to reduce
      prescription gaps and non-adherence. We aimed to assess the prevalence of the
      combined use of aspirin, statin, and BP-lowering agents in patients with
      established cardiovascular diseases or type 2 diabetes mellitus (DM2) in the
      period 1996-2009. METHODS: In total, 5702 patients with coronary artery disease
      (CAD), cerebrovascular disease (CVD), peripheral arterial occlusive disease
      (PAOD), abdominal aortic aneurysm (AAA) or, DM2 were included in the period 1996
      2009. RESULTS: The overall use of combination therapy with aspirin, statin, and
      >= 1 BP-lowering agent increased substantially from 9% in 1996 to 66% in 2009 and
      >= 2 BP-lowering agents increased from 1% to 47%. In 2009, combination therapy
      with >= 1 BP-lowering agent was used by 83% of those with CAD, 48% of those with
      CVD, 43% of those with PAOD, 36% of the patients with AAA, and 19% of the
      patients with DM2. In most patient groups, obesity, metabolic syndrome,
      hypertension concomitant CAD, CVD, or DM2 were related to the use of combination
      therapy in models adjusted for age and gender. CONCLUSION: A high proportion of
      patients with established cardiovascular diseases already uses a combination of
      pharmacological agents. Introduction of a polypill in high-risk patients might be
      feasible to reduce prescription gaps and increase adherence to indicated therapy.

PMID- 22649124
TI  - Are physicians underestimating the challenges of hypertension management? Results
      from the Supporting Hypertension Awareness and Research Europe-wide (SHARE)
      survey.
AB  - AIMS: The Supporting Hypertension Awareness and Research Europe-wide (SHARE)
      survey aimed to qualify the key challenges that physicians face when trying to
      get patients to recommended blood pressure (BP) goals. METHODS AND RESULTS: The
      survey was open to physicians involved in the treatment of hypertension, was
      anonymous, and included 45 questions covering: physicians' demographic
      information, familiarity with BP treatment guidelines, views on the BP targets
      recommended by the 2007 European Society of Hypertension and European Society of
      Cardiology (ESH-ESC) guidelines, and perceptions on the proportion of
      'challenging patients' in hypertension management (defined as patients not
      achieving the BP goal, where the BP goal is at least <140/90 mm Hg, and <130/80
      mm Hg for patients with co-morbidities or high CV risk). Physicians significantly
      underestimated the proportions of their 'challenging patients' with hypertension
      compared with their perceptions of the proportions achieving 2007 ESH-ESC BP
      targets (p < 0.0001). The majority of cardiologists (75.5%) and general/family
      practitioners (GPs) (81.3%) as well as internists (59.3%) (p < 0.05 for
      cardiologists and GPs vs internists) felt that it was a challenge to get their
      patients to target BP, stating that only 43.2%, 57.4% and 38.2% of their
      patients, respectively, achieved these targets in practice (p < 0.05 for GPs vs
      cardiologists and internists). CONCLUSION: Physicians may underestimate the
      proportion of 'challenging patients' with hypertension and there is a need to
      improve their BP control. Increasing physicians' awareness about the risks of
      uncontrolled BP and improving compliance are two possible ways to improve
      management of hypertension.

PMID- 22649125
TI  - High aortic augmentation index predicts mortality and cardiovascular events in
      men from a general population, but not in women.
AB  - BACKGROUND: A recent meta-analysis concluded that augmentation index (AIx), a
      measure of pulse wave reflections influencing the central blood pressure, is
      related to mortality and cardiovascular disease (CVD) events and is likely to be
      clinically useful. However, prospective data based on non high-risk populations
      and women are lacking. METHODS AND RESULTS: In a random sample comprising 1300
      men and 1773 women from Copenhagen, Denmark, AIx was measured non-invasively by
      use of the SphygmoCor device. The population was followed prospectively for a
      mean of 6.5 years for all-cause mortality and a combined CVD end point (time to
      first myocardial infarction, ischaemic cerebrovascular disease, percutaneous
      coronary intervention, coronary by-pass graft, or death from any cause). In men,
      hazard ratio (HR) in highest AIx tertile vs. lowest was 1.68 (95% CI 1.02-2.76)
      for all-cause mortality and 1.60 (95% CI 1.07-2.39) for the combined CVD end
      point after multivariable adjustment for CVD risk factors. In women, however, AIx
      was not related to either outcome with adjusted HR of 0.70 (95% CI 0.46-1.05) for
      all-cause mortality and 1.12 (95% CI 0.78-1.58) for the combined CVD end point.
      CONCLUSIONS: Our findings support that AIx relates to CVD in men but question the
      value in women. This gender differences may relate to different development in
      AIx with increasing age in men and women. Further studies are needed before AIx
      can be considered in CVD risk stratification or clinical practice.

PMID- 22649127
TI  - Is graded prognostic assessment an improvement compared with radiation therapy
      oncology group's recursive partitioning analysis classification for brain
      metastases?

PMID- 22649126
TI  - A phase II study of trastuzumab emtansine in patients with human epidermal growth
      factor receptor 2-positive metastatic breast cancer who were previously treated
      with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine.
AB  - PURPOSE: To determine whether the antibody-drug conjugate trastuzumab emtansine
      (T-DM1), which combines human epidermal growth factor receptor 2 (HER2) -targeted
      delivery of the potent antimicrotubule agent DM1 with the antitumor activity of
      trastuzumab, is effective in patients with HER2-positive metastatic breast cancer
      (MBC) who have previously received all standard HER2-directed therapies. PATIENTS
      AND METHODS: In this single-arm phase II study, T-DM1 3.6 mg/kg was administered
      intravenously every 3 weeks to patients with HER2-positive MBC who had prior
      treatment with trastuzumab, lapatinib, an anthracycline, a taxane, and
      capecitabine. The primary objectives were overall response rate (ORR) by
      independent review and safety. RESULTS: Among 110 pretreated patients (median,
      seven prior agents for MBC; median follow-up, 17.4 months), the ORR was 34.5%
      (95% CI, 26.1% to 43.9%), clinical benefit rate was 48.2% (95% CI, 38.8% to
      57.9%), median progression-free survival (PFS) was 6.9 months (95% CI, 4.2 to 8.4
      months), and median duration of response was 7.2 months (95% CI, 4.6 months to
      not estimable). In patients with confirmed HER2-positive tumors (n = 80 by
      retrospective central testing), the response rate was 41.3% (95% CI, 30.4% to
      52.8%), and median PFS was 7.3 months (95% CI, 4.6 to 12.3 months). Most adverse
      events were grades 1 to 2; the most frequent grade >= 3 events were
      thrombocytopenia (9.1%), fatigue (4.5%), and cellulitis (3.6%). CONCLUSION: T-DM1
      is well tolerated and has single-agent activity in patients with HER2-positive
      MBC who have previously received both approved HER2-directed therapies and
      multiple chemotherapy agents. T-DM1 may be an effective new treatment for this
      patient population.

PMID- 22649128
TI  - Gonadotropin-releasing hormone agonists for the preservation of ovarian function
      during chemotherapy.

PMID- 22649129
TI  - Complete spontaneous regression of chronic lymphocytic leukemia.

PMID- 22649130
TI  - Discordance between conclusions stated in the abstract and conclusions in the
      article: analysis of published randomized controlled trials of systemic therapy
      in lung cancer.
AB  - PURPOSE: Clinicians may read only the abstract of an article to keep abreast of
      newly published randomized controlled trials (RCTs). However, discordances have
      been noticed in summary conclusions in the abstracts and the main body of some
      articles. This article evaluated such discordances in detail. METHODS: RCTs of
      systemic therapy for lung cancer published between 2004 and 2009 were considered.
      Conclusions in the body of the articles and those in the abstracts were graded by
      using a 7-point Likert scale; 1 for strong endorsement of the control arm, 4 for
      a neutral statement, and 7 for strong endorsement of the experimental arm.
      Conclusions were classified as discordant if the difference in scores was >= 2.
      chi(2) tests and logistic regression were used to identify factors associated
      with discordance. RESULTS: From among 114 eligible RCTs identified (90 for non
      small-cell and 24 for small-cell lung cancer), 11 (10%) articles presented
      discordant conclusions in the abstract and in the body of the articles.
      Discordance was most common when the experimental arm was strongly supported in
      the abstract but not in the body of the article (nine of 11; 82%); however, the
      converse was much less common (two of 11; 18%; P < .001). Intraclass correlations
      for the two reviewers were >= 0.9. The discordances were found to be independent
      of trial-related factors. CONCLUSION: Conclusive statements in the abstract can
      differ from those in the full text. Clinicians should use caution when they
      consider making changes in their practice on the basis of reading only the
      abstract of a published RCT.

PMID- 22649131
TI  - A prospective study of bisphosphonate use and risk of colorectal cancer.
AB  - PURPOSE: Bisphosphonates are used for the treatment of bone metastases and have
      been associated with a lower risk of breast cancer. A recent case-control study
      showed an inverse association between bisphosphonate use and colorectal cancer.
      Data from prospective cohorts are lacking. PATIENTS AND METHODS: We prospectively
      examined the relationship between bisphosphonate use and risk of colorectal
      cancer among 86,277 women enrolled onto the Nurses Health Study (NHS). Since
      1998, participants have returned biennial questionnaires in which they were
      specifically queried about the regular use of bisphosphonates. We used Cox
      proportional hazards models to calculate hazard ratios (HRs) and 95% CIs for risk
      of colorectal cancer. RESULTS: Through 2008, we documented 801 cases of
      colorectal cancer over 814,406 person-years of follow-up. The age-adjusted HR for
      women who regularly used bisphosphonates was 0.92 (95% CI, 0.73 to 1.14) and was
      further attenuated after adjustment for other risk factors (multivariate HR,
      1.04; 95% CI, 0.82 to 1.33). The risk was not influenced by duration of use
      (P(trend) = 0.79). Compared with nonusers, the multivariate-adjusted HRs of
      colorectal cancer were 1.24 (95% CI, 0.94 to 1.64) for women with 1 to 2 years of
      use, 1.16 (95% CI, 0.79 to 1.69) for 3 to 4 years of use, and 0.97 (95% CI, 0.60
      to 1.56) for >= 5 years of use. There was no association between bisphosphonate
      use and colorectal cancer within strata of other risk factors. CONCLUSION: In a
      large prospective cohort, we did not observe an association between long-term use
      of bisphosphonates and risk of colorectal cancer.

PMID- 22649132
TI  - Ocular toxicity of targeted therapies.
AB  - Molecularly targeted agents are commonly used in oncology practice, and many new
      targeted agents are currently being tested in clinical trials. Although these
      agents are thought to be more specific and less toxic then traditional cytotoxic
      chemotherapy, they are associated with a variety of toxicities, including ocular
      toxicity. Many of the molecules targeted by anticancer agents are also expressed
      in ocular tissues. We reviewed the literature for described ocular toxicities
      associated with both approved and investigational molecularly targeted agents.
      Ocular toxicity has been described with numerous approved targeted agents and
      also seems to be associated with several classes of agents currently being tested
      in early-phase clinical trials. We discuss the proposed pathogenesis, monitoring
      guidelines, and management recommendations. It is important for oncologists to be
      aware of the potential for ocular toxicity, with prompt recognition of symptoms
      that require referral to an ophthalmologist. Ongoing collaboration between
      oncologists and ocular disease specialists is critical as the use of molecularly
      targeted agents continues to expand and novel targeted drug combinations are
      developed.

PMID- 22649133
TI  - Missing data in clinical studies: issues and methods.
AB  - Missing data are a prevailing problem in any type of data analyses. A participant
      variable is considered missing if the value of the variable (outcome or
      covariate) for the participant is not observed. In this article, various issues
      in analyzing studies with missing data are discussed. Particularly, we focus on
      missing response and/or covariate data for studies with discrete, continuous, or
      time-to-event end points in which generalized linear models, models for
      longitudinal data such as generalized linear mixed effects models, or Cox
      regression models are used. We discuss various classifications of missing data
      that may arise in a study and demonstrate in several situations that the commonly
      used method of throwing out all participants with any missing data may lead to
      incorrect results and conclusions. The methods described are applied to data from
      an Eastern Cooperative Oncology Group phase II clinical trial of liver cancer and
      a phase III clinical trial of advanced non-small-cell lung cancer. Although the
      main area of application discussed here is cancer, the issues and methods we
      discuss apply to any type of study.

PMID- 22649134
TI  - Richter's syndrome with aberrant CD2 and CD4 expression.

PMID- 22649135
TI  - [18F]Fluorodeoxyglucose positron emission tomography-guided therapy in metastatic
      adrenocortical carcinoma: an illustrative case.

PMID- 22649136
TI  - Long-term results of CCG 5942: a randomized comparison of chemotherapy with and
      without radiotherapy for children with Hodgkin's lymphoma--a report from the
      Children's Oncology Group.
AB  - PURPOSE: In 1995, the Children's Cancer Group (CCG) opened a trial for patients
      with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation
      therapy (IFRT) improved event-free survival (EFS) for patients achieving a
      complete response after chemotherapy. We present the long-term study outcome
      using final data through March 2007. PATIENTS AND METHODS: Between January 1995
      and December 1998, 826 eligible patients were enrolled onto CCG 5942. Four
      hundred ninety-eight patients achieving an initial complete response to
      chemotherapy were randomly assigned to receive IFRT or no further therapy. EFS
      and overall survival (OS) were assessed from the date of study entry or random
      assignment, as appropriate. RESULTS: Ten-year EFS and OS rates for the entire
      cohort were 83.5% and 92.5%, respectively. In an as-treated analysis for randomly
      assigned patients, the 10-year EFS and OS rates were 91.2% and 97.1%,
      respectively, for IFRT and 82.9% and 95.9%, respectively, for no further therapy.
      For EFS and OS comparisons, P = .004 and P = .50, respectively. Bulk disease, "B"
      symptoms, and nodular sclerosis histology were risk factors for inferior EFS.
      CONCLUSION: With a median follow-up of 7.7 years, IFRT produced a statistically
      significant improvement in EFS but no improvement in OS. For individual patients,
      the relative risks of relapse versus late effects of IFRT must be considered.
      Patient and disease characteristics and early response assessment will aid in
      deciding which patients are most likely to benefit from IFRT.

PMID- 22649137
TI  - Successful treatment with tacrolimus of a patient with severe idiopathic
      thrombocytopenic purpura after allogeneic bone marrow transplantation.

PMID- 22649138
TI  - Increased body mass index is associated with improved survival in United States
      veterans with diffuse large B-cell lymphoma.
AB  - PURPOSE: Obesity increases the risk of death from many malignancies, including
      non-Hodgkin's lymphoma (NHL). In diffuse large B-cell lymphoma (DLBCL), the most
      common form of NHL, the association between body mass index (BMI) at diagnosis
      and survival is unclear. PATIENTS AND METHODS: We evaluated the association
      between BMI at diagnosis and overall survival in a retrospective cohort of 2,534
      United States veterans diagnosed with DLBCL between October 1, 1998 and December
      31, 2008. Cox modeling was used to control for patient- and disease-related
      prognostic variables. RESULTS: Mean age at diagnosis was 68 years (range, 20 to
      100 years); 64% of patients were overweight (BMI, 25 to < 30) or obese (BMI, >=
      30). Obese patients were significantly younger, had significantly fewer B
      symptoms, and trended toward lower-stage disease, compared with other BMI groups.
      Cox analysis showed reduced mortality in overweight and obese patients
      (overweight: hazard ratio [HR], 0.73; 95% CI, 0.65 to 0.83; obese: HR, 0.68; 95%
      CI, 0.58 to 0.80), compared with normal-weight patients (BMI, 18.5 to < 25).
      Treatment during the rituximab era reduced the risk of death without affecting
      the association between BMI and survival. Disease-related weight loss occurred in
      29% of patients with weight data 1 year before diagnosis. Cox analysis based on
      BMI 1 year before diagnosis continued to demonstrate reduced risk of death in
      overweight and obese patients. CONCLUSION: Being overweight or obese at the time
      of DLBCL diagnosis is associated with improved overall survival. Understanding
      the mechanisms responsible for this association will require further study.

PMID- 22649139
TI  - Is there a difference in demography and clinical characteristics in patients
      treated with and without bevacizumab?

PMID- 22649141
TI  - Reversible posterior leukoencephalopathy syndrome and bevacizumab in breast
      cancer.

PMID- 22649140
TI  - Bayesian adaptive randomized trial design for patients with recurrent
      glioblastoma.
AB  - PURPOSE: To evaluate whether the use of Bayesian adaptive randomized (AR) designs
      in clinical trials for glioblastoma is feasible and would allow for more
      efficient trials. PATIENTS AND METHODS: We generated an adaptive randomization
      procedure that was retrospectively applied to primary patient data from four
      separate phase II clinical trials in patients with recurrent glioblastoma. We
      then compared AR designs with more conventional trial designs by using realistic
      hypothetical scenarios consistent with survival data reported in the literature.
      Our primary end point was the number of patients needed to achieve a desired
      statistical power. RESULTS: If our phase II trials had been a single, multiarm
      trial using AR design, 30 fewer patients would have been needed compared with a
      multiarm balanced randomized (BR) design to attain the same power level. More
      generally, Bayesian AR trial design for patients with glioblastoma would result
      in trials with fewer overall patients with no loss in statistical power and in
      more patients being randomly assigned to effective treatment arms. For a 140
      patient trial with a control arm, two ineffective arms, and one effective arm
      with a hazard ratio of 0.6, a median of 47 patients would be randomly assigned to
      the effective arm compared with 35 in a BR trial design. CONCLUSION: Given the
      desire for control arms in phase II trials, an increasing number of experimental
      therapeutics, and a relatively short time for events, Bayesian AR designs are
      attractive for clinical trials in glioblastoma.

PMID- 22649142
TI  - Finding the balance in pediatric Hodgkin's lymphoma.

PMID- 22649143
TI  - Sarcopenia during androgen-deprivation therapy for prostate cancer.
AB  - PURPOSE: To characterize changes in lean body mass (LBM) in men with prostate
      cancer receiving androgen-deprivation therapy (ADT). PATIENTS AND METHODS: We
      prospectively evaluated LBM in a prespecified substudy of a randomized controlled
      trial of denosumab to prevent fractures in men receiving ADT for nonmetastatic
      prostate cancer. LBM was measured by total-body dual-energy x-ray absorptiometry
      at study baseline and at 12, 24, and 36 months. The analyses included 252
      patients (132, denosumab; 120, placebo) with a baseline and at least one on-study
      LBM assessment. Patients were stratified by age (< 70 v >= 70 years) and by ADT
      duration (<= 6 v > 6 months). RESULTS: Median ADT duration was 20.4 months at
      study baseline. Mean LBM decreased significantly from baseline, by 1.0% at month
      12 (95% CI, 0.4% to 1.5%; P < .001; n = 248), by 2.1% at month 24 (95% CI, 1.5%
      to 2.7%; P < .001; n = 205), and by 2.4% at month 36 (95% CI, 1.6% to 3.2%; P <
      .001; n = 168). Men age >= 70 years (n = 127) had significantly greater changes
      in LBM at all measured time points than younger men. At 36 months, LBM decreased
      by 2.8% in men age >= 70 years and by 0.9% in younger men (P = .035). Men with <=
      6 months of ADT at study entry (n = 36) had a greater rate of decrease in LBM
      compared with men who had received more than 6 months of ADT at study entry (3.7%
      v 2.0%; P = .0645). CONCLUSION: In men receiving ADT, LBM decreased significantly
      after 12, 24, and 36 months.

PMID- 22649145
TI  - Gonadotropin-releasing hormone agonist for preservation of ovarian function
      during (neo)adjuvant chemotherapy for breast cancer.

PMID- 22649144
TI  - Targeting the B-cell lymphoma/leukemia 2 family in cancer.
AB  - The B-cell lymphoma/leukemia 2 (BCL-2) family of proteins has attracted the
      attention of cancer biologists since the cloning of BCL-2 more than 25 years ago.
      In the intervening decades, the way the BCL-2 family controls commitment to
      programmed cell death has been greatly elucidated. Several drugs directed at
      inhibiting BCL-2 and related antiapoptotic proteins have been tested clinically,
      with some showing considerable promise, particularly in lymphoid malignancies. A
      better understanding of the BCL-2 family has also provided insight into how
      conventional chemotherapy selectively kills cancer cells and why some cancers are
      more chemosensitive than others. Further exploitation of our understanding of the
      BCL-2 family promises to offer improved predictive biomarkers for oncologists and
      improved therapies for patients with cancer.

PMID- 22649146
TI  - HER2 mutations in non-small-cell lung cancer can be continually targeted.

PMID- 22649148
TI  - Potential late effect of gonadotropin-releasing hormone agonists in combination
      with chemotherapy for early breast cancer.

PMID- 22649147
TI  - Male reproductive health after childhood, adolescent, and young adult cancers: a
      report from the Children's Oncology Group.
AB  - The majority of children, adolescents, and young adults diagnosed with cancer
      will become long-term survivors. Although cancer therapy is associated with many
      adverse effects, one of the primary concerns of young male cancer survivors is
      reproductive health. Future fertility is often the focus of concern; however, it
      must be recognized that all aspects of male health, including pubertal
      development, testosterone production, and sexual function, can be impaired by
      cancer therapy. Although pretreatment strategies to preserve reproductive health
      have been beneficial to some male patients, many survivors remain at risk for
      long-term reproductive complications. Understanding risk factors and monitoring
      the reproductive health of young male survivors are important aspects of follow
      up care. The Children's Oncology Group Long-Term Follow-Up Guidelines for
      Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines)
      were created by the COG to provide recommendations for follow-up care of
      survivors at risk for long-term complications. The male health task force of the
      COG-LTFU Guidelines, composed of pediatric oncologists, endocrinologists, nurse
      practitioners, a urologist, and a radiation oncologist, is responsible for
      updating the COG-LTFU Guidelines every 2 years based on literature review and
      expert consensus. This review summarizes current task force recommendations for
      the assessment and management of male reproductive complications after treatment
      for childhood, adolescent, and young adult cancers. Issues related to male health
      that are being investigated, but currently not included in the COG-LTFU
      Guidelines, are also discussed. Ongoing investigation will inform future COG-LTFU
      Guideline recommendations for follow-up care to improve health and quality of
      life for male survivors.

PMID- 22649150
TI  - If I paint a rosy picture, will you promise not to cry?

PMID- 22649149
TI  - Giant-cell tumor of the tendon sheath in the upper cervical spine.

PMID- 22649151
TI  - Primary squamous cell carcinoma of the thyroid with cardiac metastases and right
      ventricle outflow tract obstruction.

PMID- 22649153
TI  - Recognition and handling of discordant negative human epidermal growth factor
      receptor 2 classification by Oncotype DX in patients with breast cancer.

PMID- 22649152
TI  - Pathologic complete response predicts recurrence-free survival more effectively
      by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN
      6657.
AB  - PURPOSE: Neoadjuvant chemotherapy for breast cancer provides critical information
      about tumor response; how best to leverage this for predicting recurrence-free
      survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial
      Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis)
      was a multicenter breast cancer study integrating clinical, imaging, and genomic
      data to evaluate pathologic response, RFS, and their relationship and
      predictability based on tumor biomarkers. PATIENTS AND METHODS: Eligible patients
      had tumors >= 3 cm and received neoadjuvant chemotherapy. We determined
      associations between pathologic complete response (pCR; defined as the absence of
      invasive cancer in breast and nodes) and RFS, overall and within receptor
      subsets. RESULTS: In 221 evaluable patients (median tumor size, 6.0 cm; median
      age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis
      profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal
      growth factor receptor 2 (HER2) positive. For 190 patients treated without
      neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients
      (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR
      predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard
      ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more
      predictive of RFS by multivariate analysis when subtype was taken into account,
      and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard
      ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio,
      0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01
      to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within
      subsets. CONCLUSION: In this biologically high-risk group, pCR differs by
      receptor subset. pCR is more highly predictive of RFS within every established
      receptor subset than overall, demonstrating that the extent of outcome advantage
      conferred by pCR is specific to tumor biology.

PMID- 22649154
TI  - Does pharmacodynamic interaction of nonenzymatic antioxidants modify response to
      antioxidant therapy in the process of atherosclerosis?
AB  - A discrepancy exists between clinical trials and epidemiological studies on the
      effect of antioxidants on cardiovascular disease. This discrepancy could be
      attributed to the lack of knowledge on the effect of interaction of exogenous
      antioxidant supplementation with one another or on the effect of interaction of
      exogenously administered antioxidant vitamins with endogenous ones. This study
      attempts a systematic review of available data on possible synergistic, additive,
      or antagonistic action of nonenzymatic antioxidants in atherosclerosis.
      Electronic databases were searched with the available search terms up to and
      including February 2010. Eligibility criteria were full publications, clinical
      trials, epidemiological studies, or in vitro or in vivo studies that investigated
      the effect of pharmacodynamic interaction of 2 or more antioxidants in the
      process of atherosclerosis and /or the mechanism of interaction. Eligible
      clinical trials should have at least 4 arms, 1 arm for the study of each
      antioxidant alone, 1 for the effect of both antioxidants, and 1 arm for the
      effect of placebo. In vitro data as well as the limited number of identified
      randomized clinical trials suggested that coadministration of antioxidants
      results in synergistic or additive interaction in the process of atherosclerosis.
      No study demonstrated antagonistic interaction between antioxidants.

PMID- 22649155
TI  - Death of teenager from a drug error a decade ago has made UK a leader in safety.

PMID- 22649156
TI  - US media organisation uses Facebook to build interest in patient harm.

PMID- 22649157
TI  - Doctors to take industrial action over pensions in June.

PMID- 22649158
TI  - Evaluation of monoclonal antibody-based immunohistochemistry for the detection of
      European and North American Porcine reproductive and respiratory syndrome virus
      and a comparison with in situ hybridization and reverse transcription polymerase
      chain reaction.
AB  - The objective of the present study was to compare the ability of 2 monoclonal
      antibodies (mAbs; SDOW17 and SR30) to detect types 1 and 2 Porcine reproductive
      and respiratory syndrome virus (PRRSV) in formalin-fixed, paraffin-embedded
      (FFPE) lung tissues by immunohistochemistry (IHC) and to compare the
      immunohistochemical results with in situ hybridization (ISH) and reverse
      transcription nested polymerase chain reaction (RT-nPCR) detection techniques.
      Lungs from 30 experimentally infected pigs (15 pigs with each genotype of PRRSV)
      and 20 naturally infected pigs (10 pigs with each genotype of PRRSV) with types 1
      and 2 PRRSV, respectively, were used for the IHC, ISH, and RT-nPCR analyses. The
      SR30 mAb-based IHC detected significantly more type 1 PRRSV-positive cells in the
      accessory and caudal lobes from the experimentally infected pigs at 7 (P = 0.025)
      and 14 (P = 0.018) days postinoculation, respectively, compared to the SDOW17 mAb
      based IHC. The results demonstrated that SR30 mAb-based IHC is useful for
      detecting both types 1 and 2 PRRSV antigen in FFPE lung tissues.

PMID- 22649159
TI  - Bovine herpesvirus 1 abortion: current prevalence in the United Kingdom and
      evidence of hematogenous spread within the fetus in natural cases.
AB  - While Bovine herpesvirus 1 (BoHV-1) has been known as a cause of bovine abortion
      for nearly 50 years, information is limited on the current prevalence of BoHV-1
      abortion in the United Kingdom, or about the mode of virus dissemination to cause
      infection of the fetus. The present study aimed to investigate these issues by
      surveying the prevalence of BoHV-1 in abortion cases in the United Kingdom, and
      comparing diagnostic methods to determine which are most efficient in BoHV-1
      induced abortion. Where BoHV-1 DNA was detected, viral load was compared in fetal
      tissues, using real-time polymerase chain reaction (PCR), supported by
      histopathology and immunohistochemistry (IHC) to investigate virus dissemination
      in bovine abortions. A total of 400 U.K. bovine abortion cases were studied; PCR
      detected BoHV-1 nucleic acids in 10 cases, suggestive histopathological lesions
      were observed in 8, and positive IHC staining was observed in 9. In routine
      diagnosis, BoHV-1 was identified in 2 of these cases, highlighting the utility of
      using molecular diagnostic tests such as real-time PCR to achieve high
      sensitivity in potentially autolyzed tissues. The study of different fetal
      samples showed the highest viral load in the liver, along with severe multifocal
      necrotic hepatitis, suggesting either a clear tropism of the virus for this organ
      or that it is the first location to be reached in the fetus. Presence of viral
      antigen in endothelial cells of the placenta, brain, or heart suggest a
      hematogenous spread of virus from placenta to the liver, through the umbilical
      vein, and then to the rest of the organs via fetal blood vessels.

PMID- 22649160
TI  - A novel papillomavirus isolated from proliferative skin lesions of a wild
      American beaver (Castor canadensis).
AB  - Cutaneous papillomatosis was diagnosed in an adult American beaver (Castor
      canadensis). Gross lesions included numerous exophytic, roughly circular, lightly
      pigmented lesions on hairless areas of fore and hind feet and the nose. The most
      significant histopathologic findings were multifocal papilliform hyperplasia of
      the superficial stratified squamous epithelium, with multifocal koilocytes, and
      multiple cells with large, darkly basophilic intranuclear inclusion bodies. A
      virus with properties consistent with papillomavirus (PV) was recovered by virus
      isolation of skin lesions, utilizing rabbit and feline kidney cell lines. The
      presence of the virus was confirmed by PV-specific polymerase chain reaction. The
      partial sequences of E1 and L1 genes did not closely match those of any PVs in
      GenBank, suggesting that this might be a new type of PV. Partial E1 and L1
      nucleotide sequences of the beaver papillomavirus (hereafter, ARbeaver-PV1) were
      used to create a phylogenetic tree employing the complete E1 and L1 open reading
      frame nucleotide sequences of 68 PVs. The phylogenetic tree placed the ARbeaver
      PV1 in a clade that included the Mupapillomavirus (HPV1 and HPV63) and
      Kappapapillomavirus (OcPV1 and SfPV1) genera. The present article confirms the
      papillomaviral etiology of cutaneous exophytic lesions in the beaver.

PMID- 22649161
TI  - Sequencing-independent method for the differentiation of the main phylogenetic
      lineages of Pasteurella multocida.
AB  - A rapid, easy method involving a polymerase chain reaction (PCR) assay followed
      by restriction fragment length polymorphism (RFLP) analysis was developed to
      differentiate the 2 phylogenetic lineages of Pasteurella multocida. The PCR
      targeted the 16S ribosomal RNA gene, and the RFLP involved separate digestions
      with HindIII, EarI, and MlsI. The method was applied to 16 isolates of P.
      multocida from different hosts and the isolates were clearly assigned to 1 of the
      2 lineages. The phylogenetic lineages did not match with the phenotypic-based
      identification at the subspecies level.

PMID- 22649163
TI  - Modification of a bifurcated stent graft for aortouniiliac endovascular aneurysm
      repair in a renal transplant patient.
AB  - INTRODUCTION: We describe a case of aortouniiliac (AUI) endovascular aortic
      aneurysm repair (EVAR) using combined iliac limb and bifurcated body stent graft
      modular system. CASE REPORT: This technique is demonstrated in a 58-year-old man
      with a 6-cm abdominal aortic aneurysm suitable for EVAR. The patient has a
      functioning cadaveric renal transplant anastamosed to the mid right external
      iliac artery, an occluded left iliac system and stenosed right iliac system. The
      renal allograft was protected with minimal passage across the transplant artery
      origin using this modified approach. The patient was successfully treated with a
      bifurcated main body deployed within a contralateral limb endoprosthesis.
      Subsequent scans confirmed no endoleaks or stent migration. CONCLUSIONS: The AUI
      conversion from existing Gore excluder stent graft system is safe and should be
      considered when faced with challenging anatomy of a pelvic renal transplant,
      slender access, and contralateral iliac occlusion.

PMID- 22649162
TI  - A randomized controlled trial of Cognitive Sensory Motor Training Therapy on the
      recovery of arm function in acute stroke patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of Cognitive
      Sensory Motor Training Therapy (Perfetti's method) vis-a-vis conventional
      occupational therapy in the recovery of arm function after acute stroke. DESIGN:
      Prospective randomized controlled trial. SETTING: Two rehabilitation centers in
      Bangkok, Thailand. SUBJECTS: Forty first-time acute stroke patients without
      severe cognitive or language impairment. INTERVENTION: All subjects were randomly
      divided into two groups; one was treated using Perfetti's method and the other
      using conventional occupational therapy. Each group underwent therapy for 30
      minutes, five times a week for four weeks. MAIN MEASURES: The primary variable
      was arm function as assessed by the Action Research Arm Test; secondary variables
      were the extended Barthel Index and the box and block test score. RESULTS: The
      intention-to-treat analysis revealed no statistically significant differences
      between the two groups at the end of treatment for any variable. CONCLUSIONS:
      There was no evidence of a difference between Cognitive Sensory Motor Training
      Therapy of Perfetti's method and conventional occupational therapy with respect
      to the restoration of hand and arm function after a stroke.

PMID- 22649164
TI  - Vein mapping prior to endovenous catheter ablation of the great saphenous vein
      predicts risk of endovenous heat-induced thrombosis.
AB  - OBJECTIVE: We investigate the value of vein mapping for predicting the risk of
      endovenous heat-induced thrombosis (EHIT) after endovenous laser treatment (EVLT)
      and radiofrequency ablation (RFA) of the great saphenous vein (GSV). METHODS: In
      all, 355 consecutive vein mappings were retrospectively analyzed. A generalized
      estimating equations approach to linear logistic regression was used to evaluate
      the variables. RESULTS: Among the 312 vein ablation of the GSV, 10 (3.2%)
      developed EHIT. When comparing the group of patients who developed EHIT versus no
      EHIT, the mean GSV diameter was 13.05 +/- 5.59 mm versus 8.39 +/- 3.38 mm (odds
      ratio [OR]: 1.25, P = .001), the presence of valvular incompetence at the
      saphenofemoral junction (SFJ) was 10.71% versus 0.44% (OR: 27.75, P =.001), and
      3.09% in RFA versus 3.33% in EVLT (OR: 1.09, P = .89). CONCLUSIONS: Patients with
      valvular insufficiency of the SFJ and a large proximal GSV diameter had a
      significantly higher risk of developing heat-induced thrombosis after endovenous
      catheter ablation.

PMID- 22649165
TI  - Endovascular abdominal aortic stent grafting in unrecognized Salmonella aortitis.
AB  - Abdominal endovascular graft infection is a rare but life-threatening
      complication of endovascular repair that can be challenging to manage. This
      report delineates the progression of a unique set of events leading to Salmonella
      graft infection and investigates current treatment options.

PMID- 22649166
TI  - Tumor-infiltrating mast cells in colorectal cancer as a poor prognostic factor.
AB  - The purpose of this study is to investigate the clinical/prognostic significance
      of tumor-infiltrating mast cells (TIMs) in patients with colorectal cancer (CRC).
      TIM infiltration in 325 stage I to III CRC specimens was detected by
      immunohistochemistry. The optimal cutpoint of TIM density was assessed by the X
      tile program. TIM infiltration in CRC was significantly higher than in normal
      colorectal tissues. According to the X-tile program, the cutpoint for high TIM
      infiltration in CRC was determined when TIM density was more than 8.0 per high
      power field. Correlation analysis between TIM density and clinicopathological
      variables demonstrated that TIM infiltration was significantly associated with
      gender, nodal status, and American Joint Committee on Cancer stage. Multivariate
      Cox regression analysis showed that high TIM infiltration was a risk factor for
      both overall survival and disease-free survival. Taken together, high TIM
      infiltration can be an independent and useful biomarker for predicting the poor
      survival of patients with CRC.

PMID- 22649167
TI  - The significance of intramammary lymph nodes in breast cancer: a systematic
      review and meta-analysis.
AB  - Intramammary lymph nodes (IntraMLNs) are frequent mostly benign incidental
      findings. However, they are clinically important because they can be the primary
      sites of metastasis and sentinel lymph nodes. Literature data regarding the
      clinical significance of IntraMLNs metastasis, however, remains controversial.
      This study aimed to perform a systematic review and meta-analysis to better
      define the prognostic value of positive IntraMLNs in patients with breast cancer.
      A systematic review of the literature without date restrictions was conducted.
      Five electronic medical databases were searched, and a hand-search of the
      reference lists of the collected articles was also performed. Studies with
      sufficient and relevant pathologic and clinical survival data were included.
      Other studies with insufficient data or normal findings were excluded. This study
      found 18 studies eligible for systematic review, 3 of which were eligible for
      outcome meta-analysis. IntraMLNs metastases were strongly correlated with
      axillary lymph nodes involvement. Positive IntraMLNs are reliable predictors of
      axillary lymph node involvement and therefore a guide for further surgical
      management of the axillary nodes. Even though it could be concluded that
      IntraMLNs metastasis is an independent predictor of outcome, this meta-analysis
      was limited because of the scarcity of data and the inconsistencies and
      heterogeneity of the outcome studies.

PMID- 22649168
TI  - Trajectory of functional decline before and after ischemic stroke: the Northern
      Manhattan Study.
AB  - BACKGROUND AND PURPOSE: Previous research in our cohort showed a delayed decline
      in functional status after first ischemic stroke. We compared the long-term
      trajectory of functional status before and after ischemic stroke. METHODS: The
      Northern Manhattan Study contains a prospective, population-based study of stroke
      free individuals age >=40 years, followed for a median of 11 years. The Barthel
      index (BI), a commonly used measure of activities of daily living, was assessed
      annually. Generalized estimating equations were used to assess functional decline
      over time before stroke and beginning 6 months after stroke. Follow-up was
      censored at the time of recurrent stroke. RESULTS: Among 3298 participants, 210
      participants had an ischemic stroke during follow-up and had poststroke BI
      assessed. Mean age (+/-SD) was 77+/-9 years, 38% were men, 52% were Hispanic, 37%
      had diabetes, and 31% had coronary artery disease. There was no difference in
      rate of functional decline over time before and after stroke (P=0.51), with a
      decline of 0.96 BI points per year before stroke (P<0.0001) and 1.24 BI points
      after stroke (P=0.001). However, when stratified by insurance status, among those
      with Medicaid or no insurance, in a fully adjusted model, there was a difference
      in slope before and after stroke (P=0.04), with a decline of 0.58 BI points per
      year before stroke (P=0.02) and 1.94 BI points after stroke (P=0.001).
      CONCLUSIONS: In this large, prospective, population-based study with long-term
      follow-up, there was a significantly steeper decline in functional status after
      ischemic stroke compared with before stroke among those with Medicaid or no
      insurance, after adjusting for confounders.

PMID- 22649169
TI  - Revascularization of collaterals for hemodynamic stroke: insight on
      pathophysiology from the carotid occlusion surgery study.

PMID- 22649170
TI  - Prostatic hyperplasia is highly associated with nocturia and excessive
      sleepiness: a cross-sectional study.
AB  - OBJECTIVES: The objective of this study is to assess the impact of nocturia on
      sleep in patients with lower urinary tract symptoms (LUTS)/benign prostatic
      enlargement (BPE) (nocturia>=2). DESIGN: Cross-sectional survey. SETTING: 798
      urologists and general practitioners randomly selected from the overall
      population of urologists and general practitioners of every French region.
      PARTICIPANTS: A total of 2179 LUTS/BPE men (aged 67.5+/-7.5 years old) were
      recruited. PRIMARY AND SECONDARY OUTCOME MEASURES: Validated patients' self
      administered questionnaires were used to assess the severity of LUTS/BPE (the
      International Prostate Symptom Score), sleep characteristics (sleep log) and
      sleep disorders (the International Classification of Sleep Disorders (ICSD-2) and
      the DSM-IV). Sleepiness was assessed with the Epworth Sleepiness Scale (ESS). The
      volume of 24 h diuresis (<or >1500 ml) was measured. RESULTS: Participants had on
      average 2.9+/-0.9 nocturia episodes (three or more episodes in 67%) and the
      International Prostate Symptom Score of 15.8+/-5.7; 60.9% complained of insomnia
      according to the ICSD-2, 7.9% of restless leg syndrome and 6.4% of obstructive
      sleep apnoea. 32.3% had excessive sleepiness (ESS >10) and 3.1% severe excessive
      sleepiness (ESS >16). Insomnia was mainly nocturnal awakenings with an average
      wake after sleep onset of 89+/-47 min. The number of episodes of nocturia per
      night correlated significantly with wake after sleep onset and ESS but not with
      total sleep time and sleep latency. CONCLUSION: Nocturia is significantly
      associated with sleep maintenance insomnia and sleepiness in men with BPE.

PMID- 22649172
TI  - 'Phaco-ECP': combined endoscopic cyclophotocoagulation and cataract surgery to
      augment medical control of glaucoma.
AB  - OBJECTIVES: Does phaco-ECP reduce intraocular pressure? Is phaco-ECP safe?
      DESIGN: Retrospective case note review of all patients undergoing phaco-ECP
      between June 2008 and June 2009. All glaucoma subtypes were included. SETTING:
      Single District General Hospital Ophthalmology Department within the UK.
      PARTICIPANTS: 58 participants case notes reviewed. Mean age 79.0 years (SD +/
      9.8). INTERVENTIONS: All patients received combined cataract surgery and
      endoscopic cyclophotocoagulation. OUTCOME MEASURES: Follow-up was 1 day, 1 week,
      1, 3, 6, 12, 18 and 24 months for intraocular pressure (IOP) measurement. Number
      of medications, visual acuity and presence of complications were also assessed.
      RESULTS: Of the 58 cases performed, 56 case notes (97%) were available for
      analysis. Mean age 79.0 years (SD +/-9.8). Mean pre-procedural IOP was 21.54 mm
      Hg (95% CI 19.86 to 23.22, n=56). Mean IOP was 14.43 mm Hg (95% CI 13.65 to
      15.21, n=53) at 18 months and 14.44 mm Hg (95% CI 13.63 to 15.25, n=41) at 24
      months. The mean drop from baseline to 18 and 24 months was 7.1 mm Hg.
      Statistically significant decrease in IOP was demonstrated at all time points
      (p<0.001). Mean medication usage was 1.97 agents (95% CI 1.69 to 2.25) at
      baseline, 1.96 agents (95% CI 1.70 to 2.22) at 18 months and 2.07 agents (95% CI
      1.76 to 2.38) at 24 months. No statistically significant change throughout.
      CONCLUSIONS: This study confirms the safety of phaco-ECP. In this case series,
      the IOP-lowering effect was significant at all time points; however, the effect
      of cataract surgery alone was not controlled. A randomised controlled trial is
      required to draw efficacy conclusions. The authors proposed endoscopic
      cyclophotocoagulation's main role is to optimise control of low-risk glaucoma of
      low-risk patients at the time of cataract surgery. However, the authors do not
      propose that phaco-ECP is a substitute for filtration surgery in high-risk eyes
      or when low target pressures (<14 mm Hg) are indicated.

PMID- 22649171
TI  - What potential research participants want to know about research: a systematic
      review.
AB  - OBJECTIVE: To establish the empirical evidence base for the information that
      participants want to know about medical research and to assess how this relates
      to current guidance from the National Research Ethics Service (NRES). DATA
      SOURCES: Medline, Web of Science, Applied Social Sciences Index and Abstracts,
      Sociological abstracts, Health Management Information Consortium, Cochrane
      Library, thesis index's, grey literature databases, reference and cited article
      lists, key journals, Google Scholar and correspondence with expert authors. STUDY
      SELECTION: Original research studies published between 1950 and October 2010 that
      asked potential participants to indicate how much or what types of information
      they wanted to be told about a research study or asked them to rate the
      importance of a specific piece of information were included. STUDY APPRAISAL AND
      SYNTHESIS METHODS: Studies were appraised based on the generalisability of
      results to the UK potential research participant population. A metadata analysis
      using basic thematic analysis was used to split results from papers into themes
      based on the sections of information that NRES recommends should be included in a
      participant information sheet. RESULTS: 14 studies were included. Of the 20
      pieces of information that NRES recommend should be included in patient
      information sheets for research pooled proportions could be calculated for seven
      themes. Results showed that potential participants wanted to be offered
      information about result dissemination (91% (95% CI 85% to 95%)), investigator
      conflicts of interest (48% (95% CI 27% to 69%)), the purpose of the study (76%
      (95% CI 27% to 100%)), voluntariness (39% (95% CI 2% to 100%)), how long the
      research would last (61% (95% CI 16% to 97%)), potential benefits (57% (95% CI 7%
      to 98%)) and confidentiality (44% (95% CI 10% to 82%)). The level of detail
      participants wanted to know was not explored comprehensively in the studies.
      There was no empirical evidence to support the level of information provision
      required by participants on the remaining seven items. CONCLUSIONS: There is
      limited empirical evidence on what potential participants want to know about
      research. The existing empirical evidence suggests that individuals may have very
      different needs and a more tailored evidence-based approach may be necessary.

PMID- 22649173
TI  - Parenteral Pethidine for labour pain relief and substance use disorder: 20-year
      follow-up cohort study in offspring.
AB  - OBJECTIVE: To determine whether use of intrapartum Pethidine pain analgesia
      increases the risk for substance use disorder in adult offspring. DESIGN:
      Analysis of data from a cohort study. SETTING: Academic hospital in Leiden, the
      Netherlands. PARTICIPANTS: 133 cases and 164 control individuals, aged 18-20
      years at follow-up. MAIN OUTCOME MEASURE: Incidence of substance use disorder or
      use of alcohol and tobacco. RESULTS: The lifetime use of addictive substances in
      children exposed to intrapartum Pethidine analgesia was 45% of 133 children
      versus 48% of 164 not-exposed subjects (adjusted OR=0.79, 95% CI 0.48 to 1.29).
      Recent use of alcohol, tobacco and hard drugs showed no statistical difference
      either. CONCLUSION: Pethidine for labour pain medication appears not to be
      associated with substance misuse or smoking in later life.

PMID- 22649174
TI  - Disability pension among young women in Sweden, with special emphasis on family
      structure: a dynamic cohort study.
AB  - OBJECTIVES: The influence of family structure on the risk of going on disability
      pension (DP) was investigated among young women by analysing a short-term and
      long-term effect, controlling for potential confounding and the 'healthy mother
      effect'. DESIGN AND PARTICIPANTS: This dynamic cohort study comprised all women
      born in Sweden between 1960 and 1979 (1.2 million), who were 20-43 years of age
      during follow-up. Their annual data were retrieved from national registers for
      the years 1993-2003. For this period, data on family structure and potential
      confounders were related to the incidence of DP the year after the exposure
      assessment. Using a modified version of the COX proportional hazard regression,
      we took into account changes in the study variables of individuals over the
      years. In addition, a 5-year follow-up was used. RESULTS: Cohabiting working
      women with children showed a decreased risk of DP in a 1-year perspective
      compared with cohabiting working women with no children, while the opposite was
      indicated in the 5-year follow-up. Lone working women with children had an
      increased risk of DP in both the short-term and long-term perspective. The risk
      of DP tended to increase with the number of children for both cohabiting and lone
      working women in the 5-year follow-up. CONCLUSIONS: The study suggests that
      parenthood contributes to increasing the risk of going on DP among young women,
      which should be valuable knowledge to employers and other policy makers. It
      remains to be analysed to what extent the high numbers of young women exiting
      from working life may be counteracted by (1) extended gender equality, (2) fewer
      work hours among fathers and mothers of young children and (3) by financial
      support to lone women with children.

PMID- 22649175
TI  - The Nordic Patient Experiences Questionnaire (NORPEQ): cross-national comparison
      of data quality, internal consistency and validity in four Nordic countries.
AB  - OBJECTIVES: To evaluate the Nordic Patient Experiences Questionnaire (NORPEQ) for
      data quality, reliability and validity following surveys of patients in Finland,
      Norway, Sweden and the Faroe Islands.   DESIGN, METHODS AND PARTICIPANTS:  The
      NORPEQ was mailed to 500 patients randomly selected after receiving inpatient
      treatment in Finland, Norway and Sweden. The NORPEQ was also included in a
      national survey in Norway and in the Faroe Islands. Dimensionality was assessed
      using principal component analysis and internal consistency by item-total
      correlation and Cronbach's alpha. Construct validity was assessed by correlating
      NORPEQ scores with variables known to be related to patient experiences. SETTING:
      Somatic hospitals in Finland, Faroe Islands, Norway and Sweden. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Item missing, internal consistency reliability and
      construct validity. RESULTS: Response rates ranged from 45.8% in Norway to 84%
      for Sweden. Levels of missing data were low for all items across the surveys.
      Principal component analysis identified one component with six experiences items.
      Mean NORPEQ scores ranged from 74 to 79 on the 0-100 scale, where 100 represents
      the best possible experiences. Cronbach's alpha ranged from 0.84 in Finland to
      0.88 in Sweden. CONCLUSIONS: The NORPEQ is a brief measure of patient experiences
      that covers important aspects of the healthcare encounter. It shows good evidence
      of reliability and validity. PRACTICE IMPLICATIONS: The NORPEQ instrument is
      recommended for cross-national comparisons of healthcare experiences for the four
      Nordic countries.

PMID- 22649176
TI  - Anxiety and depressive disorders are associated with delusional-like experiences:
      a replication study based on a National Survey of Mental Health and Wellbeing.
AB  - OBJECTIVES: There is growing evidence that delusional-like experiences (DLE) are
      associated with common mental disorders. In particular, a National Mental Health
      Survey conducted in Australia during 2007 reported an association between DLE and
      both anxiety disorder and major depressive disorder (MDD). However, the previous
      study did not examine this association with respect to subtypes of anxiety
      disorder nor with severity of MDD. The aim of this study was to examine the
      associations between DLE and both anxiety disorder and MDD in more detail based
      on an independent population sample. DESIGN: Cross-sectional study. SETTING:
      Subjects were drawn from the Australian Survey of Mental Health and Wellbeing
      1997 using a stratified multistage area sampling of persons living in private
      dwellings in all States and Territories of Australia. PARTICIPANTS: Approximately
      13 600 private dwellings were initially selected with one person aged 18 years or
      older from each dwelling invited to participate. In total, 10 641 individuals
      participated in the survey. PRIMARY AND SECONDARY OUTCOME MEASURES: The Composite
      International Diagnostic Interview was used to identify individuals with DLE and
      Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM IV)
      lifetime diagnoses of anxiety disorders and MDD. The influence of various anxiety
      disorders and MDD on DLE was assessed with logistic regression. RESULTS: Having a
      lifetime diagnosis of either any anxiety disorder or MDD was significantly
      associated with the endorsement of DLE. The association was found for each of the
      main anxiety disorders when examined separately. There was a dose-response
      relationship between increasing severity of MDD and higher odds of DLE
      endorsement. CONCLUSIONS: DLE are associated with a wide range of anxiety
      disorders and are more prevalent in those with MDD. Understanding the
      relationship between DLE, anxiety disorders and depression may provide insights
      into shared pathways that underpin both psychotic disorders and common mental
      disorders.

PMID- 22649177
TI  - Focused sonographic examination of the heart, lungs and deep veins in an
      unselected population of acute admitted patients with respiratory symptoms: a
      protocol for a prospective, blinded, randomised controlled trial.
AB  - INTRODUCTION: Patients admitted to hospital with acute respiratory symptoms
      remain a diagnostic challenge for the emergency physician. The use of focused
      sonography may improve the initial diagnostics, as most of the diseases, commonly
      seen and misdiagnosed in patients with acute respiratory symptoms, can be
      diagnosed with sonography. The protocol describes a prospective, blinded,
      randomised controlled trial that aims to assess the diagnostic impact of a
      pragmatic implementation of focused sonography of the heart, lungs and deep veins
      as a diagnostic modality in acute admitted patients with respiratory symptoms.
      METHODS AND ANALYSIS: The primary outcome of the study is the number of patients
      with a correct presumptive diagnosis within 4 h of admission to the emergency
      department. The patient is randomised to either an intervention or a control
      group. In the intervention group, the usual initial diagnostic work up is
      supplemented by focused sonographic examination of the heart, lungs and deep
      veins of the legs. In the control group, usual diagnostic work up is performed.
      The chi(2) test, alternatively the Fischer exact test will be used, to establish
      whether there is a difference in the distribution of the total number of patients
      with a correct/incorrect '4 h' presumptive diagnosis in the control group and in
      the intervention group. ETHICS AND DISSEMINATION: This clinical trial is
      performed according to the Declaration of Helsinki and has been approved by the
      Regional Scientific Ethical Committee for Southern Denmark and the Danish Data
      Protection Agency. The results of the trial will be published according to the
      CONSORT statement with the extension for pragmatic trials. The results of the
      trial will be published in a peer-reviewed scientific journal regardless of the
      outcome. TRIAL REGISTRATION NUMBER: This study is registered at
      http://clinicaltrials.gov, registration number NCT01486394.

PMID- 22649178
TI  - What is the optimal level of population alcohol consumption for chronic disease
      prevention in England? Modelling the impact of changes in average consumption
      levels.
AB  - OBJECTIVE: To estimate the impact of achieving alternative average population
      alcohol consumption levels on chronic disease mortality in England. DESIGN: A
      macro-simulation model was built to simultaneously estimate the number of deaths
      from coronary heart disease, stroke, hypertensive disease, diabetes, liver
      cirrhosis, epilepsy and five cancers that would be averted or delayed annually as
      a result of changes in alcohol consumption among English adults. Counterfactual
      scenarios assessed the impact on alcohol-related mortalities of changing (1) the
      median alcohol consumption of drinkers and (2) the percentage of non-drinkers.
      DATA SOURCES: Risk relationships were drawn from published meta-analyses. Age-
      and sex-specific distributions of alcohol consumption (grams per day) for the
      English population in 2006 were drawn from the General Household Survey 2006, and
      age-, sex- and cause-specific mortality data for 2006 were provided by the Office
      for National Statistics. RESULTS: The optimum median consumption level for
      drinkers in the model was 5 g/day (about half a unit), which would avert or delay
      4579 (2544 to 6590) deaths per year. Approximately equal numbers of deaths from
      cancers and liver disease would be delayed or averted (~2800 for each), while
      there was a small increase in cardiovascular mortality. The model showed no
      benefit in terms of reduced mortality when the proportion of non-drinkers in the
      population was increased. CONCLUSIONS: Current government recommendations for
      alcohol consumption are well above the level likely to minimise chronic disease.
      Public health targets should aim for a reduction in population alcohol
      consumption in order to reduce chronic disease mortality.

PMID- 22649179
TI  - Pareidolias: complex visual illusions in dementia with Lewy bodies.
AB  - Patients rarely experience visual hallucinations while being observed by
      clinicians. Therefore, instruments to detect visual hallucinations directly from
      patients are needed. Pareidolias, which are complex visual illusions involving
      ambiguous forms that are perceived as meaningful objects, are analogous to visual
      hallucinations and have the potential to be a surrogate indicator of visual
      hallucinations. In this study, we explored the clinical utility of a newly
      developed instrument for evoking pareidolic illusions, the Pareidolia test, in
      patients with dementia with Lewy bodies-one of the most common causes of visual
      hallucinations in the elderly. Thirty-four patients with dementia with Lewy
      bodies, 34 patients with Alzheimer's disease and 26 healthy controls were given
      the Pareidolia test. Patients with dementia with Lewy bodies produced a much
      greater number of pareidolic illusions compared with those with Alzheimer's
      disease or controls. A receiver operating characteristic analysis demonstrated
      that the number of pareidolias differentiated dementia with Lewy bodies from
      Alzheimer's disease with a sensitivity of 100% and a specificity of 88%. Full
      length figures and faces of people and animals accounted for >80% of the contents
      of pareidolias. Pareidolias were observed in patients with dementia with Lewy
      bodies who had visual hallucinations as well as those who did not have visual
      hallucinations, suggesting that pareidolias do not reflect visual hallucinations
      themselves but may reflect susceptibility to visual hallucinations. A sub
      analysis of patients with dementia with Lewy bodies who were or were not treated
      with donepzil demonstrated that the numbers of pareidolias were correlated with
      visuoperceptual abilities in the former and with indices of hallucinations and
      delusional misidentifications in the latter. Arousal and attentional deficits
      mediated by abnormal cholinergic mechanisms and visuoperceptual dysfunctions are
      likely to contribute to the development of visual hallucinations and pareidolias
      in dementia with Lewy bodies.

PMID- 22649180
TI  - Phylogenetic nomenclature, hierarchical information, and testability.

PMID- 22649181
TI  - Assessing parameter identifiability in phylogenetic models using data cloning.
AB  - The success of model-based methods in phylogenetics has motivated much research
      aimed at generating new, biologically informative models. This new computer
      intensive approach to phylogenetics demands validation studies and sound measures
      of performance. To date there has been little practical guidance available as to
      when and why the parameters in a particular model can be identified reliably.
      Here, we illustrate how Data Cloning (DC), a recently developed methodology to
      compute the maximum likelihood estimates along with their asymptotic variance,
      can be used to diagnose structural parameter nonidentifiability (NI) and
      distinguish it from other parameter estimability problems, including when
      parameters are structurally identifiable, but are not estimable in a given data
      set (INE), and when parameters are identifiable, and estimable, but only weakly
      so (WE). The application of the DC theorem uses well-known and widely used
      Bayesian computational techniques. With the DC approach, practitioners can use
      Bayesian phylogenetics software to diagnose nonidentifiability. Theoreticians and
      practitioners alike now have a powerful, yet simple tool to detect
      nonidentifiability while investigating complex modeling scenarios, where getting
      closed-form expressions in a probabilistic study is complicated. Furthermore,
      here we also show how DC can be used as a tool to examine and eliminate the
      influence of the priors, in particular if the process of prior elicitation is not
      straightforward. Finally, when applied to phylogenetic inference, DC can be used
      to study at least two important statistical questions: assessing identifiability
      of discrete parameters, like the tree topology, and developing efficient sampling
      methods for computationally expensive posterior densities.

PMID- 22649182
TI  - Dispelling myths about gender differences in smoking cessation: population data
      from the USA, Canada and Britain.
AB  - OBJECTIVES: Based mainly on findings from clinical settings, it has been claimed
      that women are less likely than men to quit smoking successfully. If true, this
      would have important implications for tobacco control interventions. The authors
      aimed to test this possibility using data from general population surveys.
      METHODS: The authors used data from major national surveys conducted in 2006-2007
      in the USA (Tobacco Use Supplement to the Current Population Survey), Canada
      (Canadian Tobacco Use Monitoring Survey) and the UK (General Household Survey) to
      estimate rates of smoking cessation by age in men and women. RESULTS: The authors
      found a pattern of gender differences in smoking cessation which was consistent
      across countries. Below age 50, women were more likely to have given up smoking
      completely than men, while among older age groups, men were more likely to have
      quit than women. Across all age groups, there was relatively little difference in
      cessation between the sexes. CONCLUSIONS: Conclusions about gender differences in
      smoking cessation should be based on evidence from the general population rather
      than from atypical clinical samples. This study has found convincing evidence
      that men in general are not more likely to quit smoking successfully than women.

PMID- 22649183
TI  - Surgical safety checklists: do they improve outcomes?
AB  - The concept of using a checklist in surgical and anaesthetic practice was
      energized by publication of the WHO Surgical Safety Checklist in 2008. It was
      believed that by routinely checking common safety issues, and by better team
      communication and dynamics, perioperative morbidity and mortality could be
      improved. The magnitude of improvement demonstrated by the WHO pilot studies was
      surprising. These initial results have been confirmed by further detailed work
      demonstrating that surgical checklists, when properly implemented, can make a
      substantial difference to patient safety. However, introducing surgical
      checklists is not as straightforward as it seems, and requires leadership,
      flexibility, and teamwork in a different way to that which is currently
      practiced. Future work should be aimed at ensuring effective implementation of
      the WHO Surgical Safety Checklist, which will benefit our patients on a global
      scale.

PMID- 22649184
TI  - Diagnosing postoperative neuropathic pain: a Delphi survey.
AB  - BACKGROUND: Although postoperative pain is traditionally considered to be
      nociceptive in origin, a proportion of patients experience a significant
      neuropathic component to their pain experience. Diagnosing neuropathic pain in
      this setting is challenging, and there are no published guidelines or screening
      tools designed for use in the immediate postoperative setting. We hypothesized
      that acute pain specialists were diagnosing a neuropathic component to acute
      pain, and this study aimed to obtain an expert agreed list of pain
      characteristics that could be used to aid diagnosis. METHODS: A three-round
      Internet-based Delphi survey of acute pain specialists was used to generate a
      list of acute neuropathic pain characteristics, and achieve consensus on the
      importance of each item. Items were ranked on a 1-10 scale of importance, with a
      median score of >= 7 considered important and an inter-quartile range of <= 3
      indicative of consensus. Cronbach's alpha was used to investigate internal
      consistency. RESULTS: Twenty-four items were generated by round 1 of the Delphi
      survey. Fourteen panellists participated in round 2, and 10 in round 3. After
      round 3, consensus of opinion was achieved for 13 items, with nine rated as
      important in the diagnosis of acute neuropathic pain. CONCLUSIONS: The Delphi
      survey suggests that neuropathic pain in the immediate postoperative period is
      diagnosed in a different way to chronic neuropathic pain, with items such as
      response to medications considered more useful than signs such as those
      representing autonomic changes.

PMID- 22649185
TI  - How to map the evidence: the development of the systematic review in anaesthesia.
AB  - The decision of where to start a research project has been influenced by many
      factors over the years. Tradition has a large impact, but the individual
      researchers' or clinicians' personal interest has also played a major role. The
      pharmaceutical industries' interest has without doubt initiated and sponsored
      many projects in order to get new products onto the market. The lack of an
      overview and control has led to an abundance of evidence within certain areas of
      our specialty, whereas other areas are scarcely, or not at all, researched. One
      way of 'mapping' the evidence in order to find out what we know and what we do
      not know is the production of systematic reviews. Although systematic reviews are
      considered top of the evidence hierarchy, they are not flawless. The aim of this
      article is to explain the systematic review and point to some of the challenges
      in the development and use of systematic reviews.

PMID- 22649186
TI  - Metabolomic response of human embryonic stem cell-derived germ-like cells after
      exposure to steroid hormones.
AB  - To assess the potential risks of human exposure to endocrine active compounds
      (EACs), the mechanisms of toxicity must first be identified and characterized.
      Currently, there are no robust in vitro models for identifying the mechanisms of
      toxicity in germ cells resulting from EAC exposure. Human embryonic stem cells
      can differentiate into numerous functional cell types including germ-like cells
      (GLCs). These cells possess characteristics indicative of a germ cell state,
      suggesting they offer a novel system to investigate the consequences of chemical
      exposure on normal germ cell processes. To characterize these processes, a
      metabolomic-based approach was employed to determine the response of GLCs
      following exposure to 0.001, 0.01, 0.1, 1, 10, or 100uM estradiol, testosterone,
      or progesterone for 48h. Following exposure, cellular extracts underwent gas
      chromatography coupled with mass spectrometry analysis. Models were then
      constructed using principal component analysis on acquired spectra to
      discriminate among steroid hormones as well as doses for each hormone. t-test
      comparisons generated a preliminary list of metabolites that were statistically
      significant in GLC's biochemical response to these steroid hormones. Steroid
      hormone exposures caused fluxes in intracellular pathways such as amino acid
      synthesis and metabolism, fatty acid synthesis, as well as cholesterol and
      lipoprotein metabolism. Further pathway analysis, based on these identified
      metabolites, will aid in modeling the response of GLCs to endogenous steroid
      hormones and allow for identification of biomarkers delineating germ cell-based
      developmental and reproductive pathways.

PMID- 22649187
TI  - Impact of chemical proportions on the acute neurotoxicity of a mixture of seven
      carbamates in preweanling and adult rats.
AB  - Statistical design and environmental relevance are important aspects of studies
      of chemical mixtures, such as pesticides. We used a dose-additivity model to test
      experimentally the default assumptions of dose additivity for two mixtures of
      seven N-methylcarbamates (carbaryl, carbofuran, formetanate, methomyl,
      methiocarb, oxamyl, and propoxur). The best-fitting models were selected for the
      single-chemical dose-response data and used to develop a combined prediction
      model, which was then compared with the experimental mixture data. We evaluated
      behavioral (motor activity) and cholinesterase (ChE)-inhibitory (brain, red blood
      cells) outcomes at the time of peak acute effects following oral gavage in adult
      and preweanling (17 days old) Long-Evans male rats. The mixtures varied only in
      their mixing ratios. In the relative potency mixture, proportions of each
      carbamate were set at equitoxic component doses. A California environmental
      mixture was based on the 2005 sales of each carbamate in California. In adult
      rats, the relative potency mixture showed dose additivity for red blood cell ChE
      and motor activity, and brain ChE inhibition showed a modest greater-than
      additive (synergistic) response, but only at a middle dose. In rat pups, the
      relative potency mixture was either dose-additive (brain ChE inhibition, motor
      activity) or slightly less-than additive (red blood cell ChE inhibition). On the
      other hand, at both ages, the environmental mixture showed greater-than additive
      responses on all three endpoints, with significant deviations from predicted at
      most to all doses tested. Thus, we observed different interactive properties for
      different mixing ratios of these chemicals. These approaches for studying
      pesticide mixtures can improve evaluations of potential toxicity under varying
      experimental conditions that may mimic human exposures.

PMID- 22649188
TI  - Elevated hepatic iron activates NF-E2-related factor 2-regulated pathway in a
      dietary iron overload mouse model.
AB  - Hepatic iron overload has been associated classically with the genetic disorder
      hereditary hemochromatosis. More recently, it has become apparent that mild-to
      moderate degrees of elevated hepatic iron stores observed in other liver diseases
      also have clinical relevance. The goal was to use a mouse model of dietary
      hepatic iron overload and isobaric tag for relative and absolute quantitation
      proteomics to identify, at a global level, differentially expressed proteins in
      livers from mice fed a control or 3,5,5-trimethyl-hexanoyl-ferrocene (TMHF)
      supplemented diet for 4 weeks. The expression of 74 proteins was altered by >= +/
      1.5-fold, showing that the effects of iron on the liver proteome were extensive.
      The top canonical pathway altered by TMHF treatment was the NF-E2-related factor
      2 (NRF2-)-mediated oxidative stress response. Because of the long-standing
      association of elevated hepatic iron with oxidative stress, the remainder of the
      study was focused on NRF2. TMHF treatment upregulated 25 phase I/II and
      antioxidant proteins previously categorized as NRF2 target gene products.
      Immunoblot analyses showed that TMHF treatment increased the levels of
      glutathione S-transferase (GST) M1, GSTM4, glutamate-cysteine ligase (GCL)
      catalytic subunit, GCL modifier subunit, glutathione synthetase, glutathione
      reductase, heme oxygenase 1, epoxide hydrolase 1, and NAD(P)H dehydrogenase
      quinone 1. Immunofluorescence, carried out to determine the cellular localization
      of NRF2, showed that NRF2 was detected in the nucleus of hepatocytes from TMHF
      treated mice and not from control mice. We conclude that elevated hepatic iron in
      a mouse model activates NRF2, a key regulator of the cellular response to
      oxidative stress.

PMID- 22649189
TI  - Matrix modulation of the bioactivation of estragole by constituents of different
      alkenylbenzene-containing herbs and spices and physiologically based biokinetic
      modeling of possible in vivo effects.
AB  - The alkenylbenzene estragole is a constituent of several herbs and spices. It
      induces hepatomas in rodents at high doses following bioactivation by cytochrome
      P450s and sulfotransferases (SULTs) giving rise to the ultimate carcinogenic
      metabolite 1'-sulfooxyestragole which forms DNA adducts. Methanolic extracts from
      different alkenylbenzene-containing herbs and spices were able to inhibit SULT
      activity. Flavonoids including quercetin, kaempferol, myricetin, apigenin, and
      nevadensin were the major constituents responsible for this inhibition with Ki
      values in the nano to micromolar range. In human HepG2 cells exposed to the
      proximate carcinogen 1'-hydroxyestragole, the various flavonoids were able to
      inhibit estragole DNA adduct formation and shift metabolism in favor of
      glucuronidation which is a detoxification pathway for 1'-hydroxyestragole. In a
      next step, the kinetics for SULT inhibition were incorporated in physiologically
      based biokinetic (PBBK) models for estragole in rat and human to predict the
      effect of co-exposure to estragole and (mixtures of) the different flavonoids on
      the bioactivation in vivo. The PBBK-model-based predictions indicate that the
      reduction of estragole bioactivation in rat and human by co-administration of the
      flavonoids is dependent on whether the intracellular liver concentrations of the
      flavonoids can reach their Ki values. It is expected that this is most easily
      achieved for nevadensin which has a Ki value in the nanomolar range and is, due
      to its methyl ation, more metabolically stable than the other flavonoids.

PMID- 22649190
TI  - Molecular identification of GD3 as a suppressor of the innate immune response in
      ovarian cancer.
AB  - Tumors often display mechanisms to avoid or suppress immune recognition. One such
      mechanism is the shedding of gangliosides into the local tumor microenvironment,
      and a high concentration of circulating gangliosides is associated with poor
      prognosis. In this study, we identify ganglioside GD3, which was isolated from
      the polar lipid fraction of ovarian cancer-associated ascites, as an inhibitory
      factor that prevents innate immune activation of natural killer T (NKT) cells.
      Purified GD3 displayed a high affinity for both human and mouse CD1d, a molecule
      involved in the presentation of lipid antigens to T cells. Purified GD3, as well
      as substances within the ascites, bound to the CD1d antigenic-binding site and
      did not require additional processing for its inhibitory effect on NKT cells.
      Importantly, in vivo administration of GD3 inhibited alpha-galactosylceramide
      (alpha-GalCer)-induced NKT cell activation in a dose-dependent manner. These data
      therefore indicate that ovarian cancer tumors may use GD3 to inhibit the
      antitumor NKT cell response as an early mechanism of tumor immune evasion.

PMID- 22649191
TI  - GITR ligand provided by thrombopoietic cells inhibits NK cell antitumor activity.
AB  - Thrombocytopenia inhibits tumor growth and especially metastasis in mice, whereas
      additional depletion of NK cells reverts this antimetastatic phenotype. It has
      therefore been speculated that platelets may protect hematogenously disseminating
      tumor cells from NK-dependent antitumor immunity. Tumor cells do not travel
      through the blood alone, but are rapidly coated by platelets, and this phenomenon
      has been proposed to shield disseminating tumor cells from NK-mediated lysis.
      However, the underlying mechanisms remain largely unclear. In this study, we show
      that megakaryocytes acquire expression of the TNF family member glucocorticoid
      induced TNF-related ligand (GITRL) during differentiation, resulting in GITRL
      expression by platelets. Upon platelet activation, GITRL is upregulated on the
      platelet surface in parallel with the alpha-granular activation marker P
      selectin. GITRL is also rapidly mobilized to the platelet surface following
      interaction with tumor cells, which results in platelet coating. Whereas GITRL,
      in the fashion of several other TNF family members, is capable of transducing
      reverse signals, no influence on platelet activation and function was observed
      upon GITRL triggering. However, platelet coating of tumor cells inhibited NK cell
      cytotoxicity and IFN-gamma production that could partially be restored by
      blocking GITR on NK cells, thus indicating that platelet-derived GITRL mediates
      NK-inhibitory forward signaling via GITR. These data identify conferment of GITRL
      pseudoexpression to tumor cells by platelets as a mechanism by which platelets
      may alter tumor cell immunogenicity. Our data thus provide further evidence for
      the involvement of platelets in facilitating evasion of tumor cells from NK cell
      immune surveillance.

PMID- 22649192
TI  - Identification of resting and type I IFN-activated human NK cell miRNomes reveals
      microRNA-378 and microRNA-30e as negative regulators of NK cell cytotoxicity.
AB  - NK cells are important innate immune cells with potent cytotoxicity that can be
      activated by type I IFN from the host once infected. How NK cell cytotoxicity is
      activated by type I IFN and then tightly regulated remain to be fully elucidated.
      MicroRNAs (miRNAs, or miRs) are important regulators of innate immune response,
      but the full scale of miRNome in human NK cells remains to be determined. In this
      study, we reported an in-depth analysis of miRNomes in resting and IFN-alpha
      activated human NK cells, found two abundant miRNAs, miR-378 and miR-30e,
      markedly decreased in activated NK cells by IFN-alpha, and further proved that
      miR-378 and miR-30e directly targeted granzyme B and perforin, respectively.
      Thus, IFN-alpha activation suppresses miR-378 and miR-30e expression to release
      cytolytic molecule mRNAs for their protein translation and then augments NK cell
      cytotoxicity. Importantly, the phenomena are also confirmed in human NK cells
      activated by other cytokines and even in the sorted CD16(+)CD56(dim)CD69(+) human
      NK cell subset. Finally, miR-378 and miR-30e were proved to be suppressors of
      human NK cell cytotoxicity. Taken together, our results reveal that downregulated
      miR-378 and miR-30e during NK cell activation are negative regulators of human NK
      cell cytotoxicity, providing a mechanistic explanation for regulation of NK cell
      function by miRNAs.

PMID- 22649193
TI  - The aryl hydrocarbon receptor modulates acute and late mast cell responses.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor
      whose activity is modulated by xenobiotics as well as physiological ligands.
      These compounds may modulate inflammatory responses and contribute to the rising
      prevalence of allergic diseases observed in industrialized countries. Mast cells
      (MCs), located within tissues at the boundary of the external environment,
      represent a potential target of AhR ligands. In this study, we report that murine
      and human MCs constitutively express AhR, and its activation by the high-affinity
      ligand 6-formylindolo[3,2-b]carbazole (FICZ) determines a boost in degranulation.
      On the contrary, repeated exposure to FICZ inhibits MC degranulation.
      Accordingly, histamine release, in an in vivo passive systemic anaphylactic
      model, is exacerbated by a single dose and is attenuated by repetitive
      stimulation of AhR. FICZ-exposed MCs produce reactive oxygen species and IL-6 in
      response to cAMP-dependent signals. Moreover, AhR-activated MCs produce IL-17, a
      critical player in chronic inflammation and autoimmunity, suggesting a novel
      pathway for MC activation in the pathogenesis of these diseases. Indeed,
      histological analysis of patients with chronic obstructive pulmonary disease
      revealed an enrichment in AhR/IL-6 and AhR/IL-17 double-positive MCs within
      bronchial lamina propria. Thus, tissue-resident MCs could translate external
      chemical challenges through AhR by modulating allergic responses and contributing
      to the generation of inflammation-related diseases.

PMID- 22649194
TI  - Cutting edge: TNF receptor-associated factor 4 restricts IL-17-mediated pathology
      and signaling processes.
AB  - The effector T cell subset, Th17, plays a significant role in the pathogenesis of
      multiple sclerosis and of other autoimmune diseases. The signature cytokine, IL
      17, engages the IL-17R and recruits the E3-ligase NF-kappaB activator 1 (Act1)
      upon stimulation. In this study, we examined the role of TNFR-associated factor
      (TRAF)4 in IL-17 signaling and Th17-mediated autoimmune encephalomyelitis.
      Primary cells from TRAF4-deficient mice displayed markedly enhanced IL-17
      activated signaling pathways and induction of chemokine mRNA. Adoptive transfer
      of MOG35-55 specific wild-type Th17 cells into TRAF4-deficient recipient mice
      induced an earlier onset of disease. Mechanistically, we found that TRAF4 and
      TRAF6 used the same TRAF binding sites on Act1, allowing the competition of TRAF4
      with TRAF6 for the interaction with Act1. Taken together, the results of this
      study reveal the necessity of a unique role of TRAF4 in restricting the effects
      of IL-17 signaling and Th17-mediated disease.

PMID- 22649195
TI  - Relative contributions of dectin-1 and complement to immune responses to
      particulate beta-glucans.
AB  - Glucan particles (GPs) are Saccharomyces cerevisiae cell walls chemically
      extracted so they are composed primarily of particulate beta-1,3-D-glucans. GPs
      are recognized by Dectin-1 and are potent complement activators. Mice immunized
      with Ag-loaded GPs develop robust Ab and CD4(+) T cell responses. In this study,
      we examined the relative contributions of Dectin-1 and complement to GP
      phagocytosis and Ag-specific responses to immunization with OVA encapsulated in
      GPs. The in vitro phagocytosis of GPs by bone marrow-derived dendritic cells was
      facilitated by heat-labile serum component(s) independently of Dectin-1. This
      enhanced uptake was not seen with serum from complement component 3 knockout (C3(
      /-)) mice and was also inhibited by blocking Abs directed against complement
      receptor 3. After i.p. injection, percent phagocytosis of GPs by peritoneal
      macrophages was comparable in wild-type and Dectin-1(-/-) mice and was not
      inhibited by the soluble beta-glucan antagonist laminarin. In contrast, a much
      lower percentage of peritoneal macrophages from C3(-/-) mice phagocytosed GPs,
      and this percentage was further reduced in the presence of laminarin.
      Subcutaneous immunization of wild-type, Dectin-1(-/-), and C3(-/-) mice with GP
      OVA resulted in similar Ag-specific IgG(1) and IgG(2c) type Ab and CD4(+) T cell
      lymphoproliferative responses. Moreover, while CD4(+) Th1 and Th2 responses
      measured by ELISPOT assay were similar in the three mouse strains, Th17 responses
      were reduced in C3(-/-) mice. Thus, although Dectin-1 is necessary for optimal
      phagocytosis of GPs in the absence of complement, complement dominates when both
      an intact complement system and Dectin-1 are present. In addition, Th-skewing
      after GP-based immunization was altered in C3(-/-) mice.

PMID- 22649196
TI  - Purinergic P2X7 receptor drives T cell lineage choice and shapes peripheral
      gammadelta cells.
AB  - TCR signal strength instructs alphabeta versus gammadelta lineage decision in
      immature T cells. Increased signal strength of gammadeltaTCR with respect to pre
      TCR results in induction of the gammadelta differentiation program. Extracellular
      ATP evokes physiological responses through purinergic P2 receptors expressed in
      the plasma membrane of virtually all cell types. In peripheral T cells, ATP
      released upon TCR stimulation enhances MAPK activation through P2X receptors. We
      investigated whether extracellular ATP and P2X receptors signaling tuned TCR
      signaling at the alphabeta/gammadelta lineage bifurcation checkpoint. We show
      that P2X7 expression was selectively increased in immature gammadelta(+)CD25(+)
      cells. These cells were much more competent to release ATP than pre-TCR
      expressing cells following TCR stimulation and Ca(2+) influx. Genetic ablation as
      well as pharmacological antagonism of P2X7 resulted in impaired ERK
      phosphorylation, reduction of early growth response (Egr) transcripts induction,
      and diversion of gammadeltaTCR-expressing thymocytes toward the alphabeta lineage
      fate. The impairment of the ERK-Egr-inhibitor of differentiation 3 (Id3)
      signaling pathway in gammadelta cells from p2rx7(-/-) mice resulted in increased
      representation of the Id3-independent NK1.1-expressing gammadelta T cell subset
      in the periphery. Our results indicate that ATP release and P2X7 signaling upon
      gammadeltaTCR expression in immature thymocytes constitutes an important
      costimulus in T cell lineage choice through the ERK-Egr-Id3 signaling pathway and
      contributes to shaping the peripheral gammadelta T cell compartment.

PMID- 22649197
TI  - Donor B cells in transplants augment clonal expansion and survival of pathogenic
      CD4+ T cells that mediate autoimmune-like chronic graft-versus-host disease.
AB  - We reported that both donor CD4(+) T and B cells in transplants were required for
      induction of an autoimmune-like chronic graft-versus-host disease (cGVHD) in a
      murine model of DBA/2 donor to BALB/c recipient, but mechanisms whereby donor B
      cells augment cGVHD pathogenesis remain unknown. In this study, we report that,
      although donor B cells have little impact on acute GVHD severity, they play an
      important role in augmenting the persistence of tissue damage in the acute and
      chronic GVHD overlapping target organs (i.e., skin and lung); they also markedly
      augment damage in a prototypical cGVHD target organ, the salivary gland. During
      cGVHD pathogenesis, donor B cells are activated by donor CD4(+) T cells to
      upregulate MHC II and costimulatory molecules. Acting as efficient APCs, donor B
      cells augment donor CD4(+) T clonal expansion, autoreactivity, IL-7Ralpha
      expression, and survival. These qualitative changes markedly augment donor CD4(+)
      T cells' capacity in mediating autoimmune-like cGVHD, so that they mediate
      disease in the absence of donor B cells in secondary recipients. Therefore, a
      major mechanism whereby donor B cells augment cGVHD is through augmenting the
      clonal expansion, differentiation, and survival of pathogenic CD4(+) T cells.

PMID- 22649198
TI  - The endothelial antigen ESAM monitors hematopoietic stem cell status between
      quiescence and self-renewal.
AB  - Whereas most hematopoietic stem cells (HSC) are quiescent in homeostasis, they
      actively proliferate in response to bone marrow (BM) injury. Signals from the BM
      microenvironment are thought to promote entry of HSC into the cell cycle.
      However, it has been cumbersome to assess cycle status of viable HSC and thus
      explore unique features associated with division. In this study, we show that
      expression of endothelial cell-selective adhesion molecule (ESAM) can be a
      powerful indicator of HSC activation. ESAM levels clearly mirrored the shift of
      HSC between quiescence and activation, and it was prominent in comparison with
      other HSC-related Ags. ESAM(hi) HSC were actively dividing, but had surprisingly
      high long-term reconstituting capacity. Immunohistochemical analyses showed that
      most ESAM(hi) HSC were located near vascular endothelium in the BM after 5
      fluorouracil treatment. To determine the importance of ESAM in the process of BM
      recovery, ESAM knockout mice were treated with 5-fluorouracil and their
      hematopoietic reconstruction was examined. The ESAM deficiency caused severe and
      prolonged BM suppression, suggesting that ESAM is functionally indispensable for
      HSC to re-establish homeostatic hematopoiesis. With respect to intracellular
      regulators, NF-kappaB and topoisomerase II levels correlated with the ESAM
      upregulation. Thus, our data demonstrate that the intensity of ESAM expression is
      useful to trace activated HSC and to understand molecular events involved in stem
      cell states.

PMID- 22649199
TI  - CD8+ Foxp3+ regulatory T cells are induced during graft-versus-host disease and
      mitigate disease severity.
AB  - Regulatory T cells (Tregs), in particular CD4(+) Foxp3(+) T cells, have been
      shown to play an important role in the maintenance of tolerance after allogeneic
      stem cell transplantation. In the current study, we have identified a population
      of CD8(+) Foxp3(+) T cells that are induced early during graft-versus-host
      disease (GVHD), constitute a significant percentage of the entire Treg
      population, and are present in all major GVHD target organs. These cells
      expressed many of the same cell surface molecules as found on CD4(+) Tregs and
      potently suppressed in vitro alloreactive T cell responses. Induction of these
      cells correlated positively with the degree of MHC disparity between donor and
      recipient and was significantly greater than that observed for CD4(+)-induced
      Tregs (iTregs) in nearly all tissue sites. Mice that lacked the ability to make
      both CD8(+) and CD4(+) iTregs had accelerated GVHD mortality compared with
      animals that were competent to make both iTreg populations. The absence of both
      iTreg populations was associated with significantly greater expansion of
      activated donor T cells and increased numbers of CD4(+) and CD8(+) T cells that
      secreted IFN-gamma and IL-17. The presence of CD8(+) iTregs, however, was
      sufficient to prevent increased GVHD mortality in the complete absence of CD4(+)
      Tregs, indicating at least one functional iTreg population was sufficient to
      prevent an exacerbation in GVHD severity, and that CD8(+) iTregs could compensate
      for CD4(+) iTregs. These studies define a novel population of CD8(+) Tregs that
      play a role in mitigating the severity of GVHD after allogeneic stem cell
      transplantation.

PMID- 22649200
TI  - Classical ataxia telangiectasia patients have a congenitally aged immune system
      with high expression of CD95.
AB  - Ataxia-telangiectasia (A-T) is a rare neurodegenerative immunodeficiency disorder
      caused by mutations in the ataxia telangiectasia mutated gene. Patients commonly
      have lymphopenia and Ig-production abnormalities. We used multicolor flow
      cytometry and IL-7 ELISA to investigate the effect of A-T and age on the
      proportions of major lymphocyte subsets and their pattern of CD95 expression in
      relation to IL-7 levels in 15 classical A-T patients. We also analyzed the
      sensitivity of T cells from four classical A-T patients to CD95-mediated
      apoptosis using TUNEL and caspase-activation assays. Our results confirmed
      lymphopenia and a deficiency in naive T and B cells in A-T patients. In contrast
      to controls, the proportions of naive and memory T and B cell subsets in A-T
      patients did not vary in relation to age. There was no evidence of a deficiency
      in plasma IL-7 or IL-7R expression, and IL-7 concentration correlated positively
      with CD95 expression on CD4(+) T cells. CD95 expression on unstimulated A-T
      lymphocytes was high, and the apoptotic sensitivity of activated naive and
      central memory T cells was increased. These findings show that the
      immunodeficiency in A-T patients may be described as congenitally aged and is not
      progressive. The naive cell deficiency is not related to a deficiency in IL-7 or
      its receptor. However, IL-7 may upregulate CD95 on A-T lymphocytes. High CD95
      expression and increased apoptotic sensitivity of activated naive and central
      memory T cells may result in an increased level of CD95-mediated apoptosis, which
      could contribute to the congenital lymphopenia in A-T.

PMID- 22649201
TI  - Pulmonary CCL18 recruits human regulatory T cells.
AB  - CCL18 is both a constitutively expressed and an inducible chemokine, whose role
      in the inflammatory reaction is poorly known. The aim of this study was to
      evaluate whether CCL18 has the capacity to attract human T cells with a
      regulatory function (regulatory T cells [Treg]). Results from chemotaxis assays
      performed on different types of Treg showed that CD4(+)CD25(+)CD127(low) cells,
      but neither T regulatory type 1 clones nor Treg differentiated in vitro with anti
      CD3/CD46 mAbs, were recruited by CCL18 in a dose-dependent manner. CCL18
      recruited memory CD4(+) T cells were enriched in CD25(high), CD25(+)CD127(low),
      latency-associated peptide/TGF-beta1, and CCR4-expressing T cells, whereas there
      was no enrichment in Foxp3(+) cells as compared with controls. Stimulated CCL18
      recruited memory T cells produced significantly increased amounts of the
      regulatory cytokines IL-10 and TGF-beta1, as well as IL-4, but not IFN-gamma and
      IL-17. Cell surface CCL18 binding was found predominantly on IL-10(+) (26.3 +/-
      5.8%) and on a few latency-associated peptide/TGF-beta1(+) (18.1 +/- 1.9%) and IL
      4(+) (14.5 +/- 2.9%) memory T cells. In an in vivo model of SCID mice grafted
      with human skin and reconstituted with autologous PBMCs, the intradermal
      injection of CCL18 led to the cutaneous recruitment of CD4(+), CD25(+), and IL
      10(+) cells, but not Foxp3(+) cells. Furthermore, CCL18-recruited memory T cells
      inhibited the proliferation of CD4(+)CD25(-) effector T cells through an IL-10
      dependent mechanism. These data suggest that CCL18 may contribute to maintaining
      tolerance and/or suppressing deleterious inflammation by attracting memory Tregs
      into tissues, particularly in the lung, where it is highly and constitutively
      expressed.

PMID- 22649202
TI  - Fcgamma receptor IIb strongly regulates Fcgamma receptor-facilitated T cell
      activation by dendritic cells.
AB  - FcgammaR ligation by Ag-Ab immune complexes (IC) not only mediates effective Ag
      uptake, but also strongly initiates dendritic cell (DC) maturation, a requirement
      for effective T cell activation. Besides the activating FcgammaRI, FcgammaRIII,
      and FcgammaRIV, the inhibitory FcgammaRIIb is expressed on DCs. It is unclear how
      the ratio between signals from the activating FcgammaR and the inhibitory
      FcgammaRIIb determines the outcome of FcgammaR ligation on DCs. By microarray
      analysis, we compared the transcriptomes of steady state and IC-activated bone
      marrow-derived wild-type (WT) DCs expressing all FcgammaR or DCs expressing only
      activating FcgammaR (FcgammaRIIb knockout [KO]) or only the inhibitory
      FcgammaRIIb (FcR gamma-chain KO). In WT DCs, we observed a gene expression
      profile associated with effective T cell activation, which was absent in FcR
      gamma-chain KO, but strikingly more pronounced in FcgammaRIIb KO bone marrow
      derived DCs. These microarray results, confirmed at the protein level for many
      cytokines and other immunological relevant genes, demonstrate that the
      transcriptome of IC-activated DCs is dependent on the presence of the activating
      FcgammaR and that the modulation of the expression of the majority of the genes
      was strongly regulated by FcgammaRIIb. Our data suggest that FcgammaRIIb
      deficient DCs have an improved capacity to activate naive T lymphocytes. This was
      confirmed by their enhanced FcgammaR-dependent Ag presentation and in vivo
      induction of CD8(+) T cell expansion compared with WT DCs. Our findings
      underscore the potency of FcgammaR ligation on DCs for the effective induction of
      T cell immunity by ICs and the strong regulatory role of FcgammaRIIb.

PMID- 22649203
TI  - Gadolinium compounds signaling through TLR4 and TLR7 in normal human macrophages:
      establishment of a proinflammatory phenotype and implications for the
      pathogenesis of nephrogenic systemic fibrosis.
AB  - Nephrogenic systemic sibrosis is a progressive disorder occurring in some renal
      insufficiency patients exposed to gadolinium-based contrast agents (GdBCA).
      Previous studies demonstrated that the GdBCA Omniscan upregulated several innate
      immunity pathways in normal differentiated human macrophages, induced rapid
      nuclear localization of the transcription factor NF-kappaB, and increased the
      expression and production of numerous profibrotic/proinflammatory cytokines,
      chemokines, and growth factors. To further examine GdBCA stimulation of the
      innate immune system, cultured human embryonic kidney 293 cells expressing one of
      seven different human TLRs or one of two human nucleotide-binding oligomerization
      domain-like receptors were exposed in vitro for 24 h to various GdBCA. The
      signaling activity of each compound was evaluated by its ability to activate an
      NF-kappaB-inducible reporter gene. Omniscan and gadodiamide induced strong TLR4-
      and TLR7-mediated reporter gene activation. The other Gd compounds examined
      failed to induce reporter gene activation. TLR pathway inhibition using
      chloroquine or an inhibitor of IL-1R-associated kinases 1 and 4 in normal
      differentiated human macrophages abrogated Omniscan-induced gene expression.
      Omniscan and gadodiamide signaling via TLRs 4 and 7 resulted in increased
      production and expression of numerous proinflammatory/profibrotic cytokines,
      chemokines, and growth factors, including CXCL10, CCL2, CCL8, CXCL12, IL-4, IL-6,
      TGF-beta, and vascular endothelial growth factor. These observations suggest that
      TLR activation by environmental stimuli may participate in the pathogenesis of
      nephrogenic systemic fibrosis and of other fibrotic disorders including systemic
      sclerosis.

PMID- 22649205
TI  - Technical advance: decreased helper T cells and increased natural killer cells in
      chronic periodontitis analyzed by a novel method for isolating resident
      lymphocytes.
AB  - During CP, the gingival environment is primed to recruit and activate homing
      lymphocytes. However, detailed phenotypic and functional characterization of
      gingival tissue resident lymphocytes has been challenging as a result of
      limitations associated with available isolation methods and limited availability
      of human samples. This study aimed to develop a novel explant culture technique
      for effectively isolating human gingival lymphocytes. This technique takes
      advantage of the natural tendency of MNCs to migrate toward a chemokine gradient
      generated by the gingival fibroblasts. The explant system allowed isolation of
      MNCs with ~95* higher yield relative to conventional approaches. The MNC yield
      correlates directly with wet weights of the tissues, and maximal MNCs are
      isolated during the 2nd day of the culture. The explant culture method and
      conventional approach produce similar MNC subpopulations such as Th, Tc, and B
      cells. Chemokines associated with MNC migration but not cytokines associated with
      MNC proliferation and differentiation were produced in the explant culture.
      Moreover, MNC migration in response to the secreted chemokines was inhibited by
      PTX. T cells did not undergo proliferation during the culture. However, the
      isolated T cells responded to mitogenic stimulation ex vivo. A statistically,
      significantly decreased Th cell with reduced CD25 expression along with increased
      NK and NKT cells in CP are shown. However, the number of naive NK cells was
      decreased significantly in MNCs, suggesting activation of NK cells in CP.

PMID- 22649204
TI  - CD8+ T cells suppress viral replication in the cornea but contribute to VEGF-C
      induced lymphatic vessel genesis.
AB  - HSV-1 is the leading cause of infectious corneal blindness in the industrialized
      world. CD4(+) T cells are thought to be the major leukocyte population mediating
      immunity to HSV-1 in the cornea as well as the likely source of immunopathology
      that reduces visual acuity. However, the role of CD8(+) T cells in immune
      surveillance of the cornea is unclear. Thus, we sought to evaluate the role of
      CD8(+) T cells in ocular immunity using transgenic mice in which >98% of CD8(+) T
      cells are specific for the immunodominant HSV-1 epitope (gBT-I.1). We found a
      significant reduction in virus, elevation in HSV-specific CD8(+) T cell influx,
      and more CD8(+) T cells expressing CXCR3 in the cornea of transgenic mice
      compared with those in the cornea of wild-type controls yet similar acute corneal
      pathology. However, by day 30 postinfection, wild-type mice had drastically more
      blood and lymphatic vessel projections into the cornea compared with gBT-I.1
      mice, in which only lymphatic vessel growth in response to VEGF-C could be
      appreciated. Taken together, these results show that CD8(+) T cells are required
      to eliminate virus more efficiently from the cornea but play a minimal role in
      immunopathology as a source of VEGF-C.

PMID- 22649206
TI  - Psoriasis alters HDL composition and cholesterol efflux capacity.
AB  - Psoriasis, a chronic inflammatory skin disease, has been linked to increased
      myocardial infarction and stroke. Functional impairment of HDL may contribute to
      the excess cardiovascular mortality of psoriatic patients. However, data
      available regarding the impact of psoriasis on HDL composition and function are
      limited. HDL from psoriasis patients and healthy controls was isolated by
      ultracentrifugation and shotgun proteomics, and biochemical methods were used to
      monitor changed HDL composition. We observed a significant reduction in apoA-I
      levels of HDL from psoriatic patients, whereas levels of apoA-II and proteins
      involved in acute-phase response, immune response, and endopeptidase/protease
      inhibition were increased. Psoriatic HDL contained reduced phospholipid and
      cholesterol. With regard to function, these compositional alterations impaired
      the ability of psoriatic HDL to promote cholesterol efflux from macrophages.
      Importantly, HDL-cholesterol efflux capability negatively correlated with
      psoriasis area and severity index. We observed that control HDL, as well as
      psoriatic HDL, inhibited dihydrorhodamine (DHR) oxidation to a similar extent,
      suggesting that the anti-oxidative activity of psoriatic HDL is not significantly
      altered. Our observations suggest that the compositional alterations observed in
      psoriatic HDL reflect a shift to a pro-inflammatory profile that impairs
      cholesterol efflux capacity of HDL and may provide a link between psoriasis and
      cardiovascular disease.

PMID- 22649207
TI  - Sex-dependent hemispheric asymmetries for processing frequency-modulated sounds
      in the primary auditory cortex of the mustached bat.
AB  - Species-specific vocalizations of mammals, including humans, contain slow and
      fast frequency modulations (FMs) as well as tone and noise bursts. In this study,
      we established sex-specific hemispheric differences in the tonal and FM response
      characteristics of neurons in the Doppler-shifted constant-frequency processing
      area in the mustached bat's primary auditory cortex (A1). We recorded single-unit
      cortical activity from the right and left A1 in awake bats in response to the
      presentation of tone bursts and linear FM sweeps that are contained within their
      echolocation and/or communication sounds. Peak response latencies to neurons'
      preferred or best FMs were significantly longer on the right compared with the
      left in both sexes, and in males this right-left difference was also present for
      the most excitatory tone burst. Based on peak response magnitudes, right
      hemispheric A1 neurons in males preferred low-rate, narrowband FMs, whereas those
      on the left were less selective, responding to FMs with a variety of rates and
      bandwidths. The distributions of parameters for best FMs in females were similar
      on the two sides. Together, our data provide the first strong physiological
      support of a sex-specific, spectrotemporal hemispheric asymmetry for the
      representation of tones and FMs in a nonhuman mammal. Specifically, our results
      demonstrate a left hemispheric bias in males for the representation of a diverse
      array of FMs differing in rate and bandwidth. We propose that these asymmetries
      underlie lateralized processing of communication sounds and are common to species
      as divergent as bats and humans.

PMID- 22649208
TI  - The passive stiffness of the wrist and forearm.
AB  - Because wrist rotation dynamics are dominated by stiffness (Charles SK, Hogan N.
      J Biomech 44: 614-621, 2011), understanding how humans plan and execute
      coordinated wrist rotations requires knowledge of the stiffness characteristics
      of the wrist joint. In the past, the passive stiffness of the wrist joint has
      been measured in 1 degree of freedom (DOF). Although these 1-DOF measurements
      inform us of the dynamics the neuromuscular system must overcome to rotate the
      wrist in pure flexion-extension (FE) or pure radial-ulnar deviation (RUD), the
      wrist rarely rotates in pure FE or RUD. Instead, understanding natural wrist
      rotations requires knowledge of wrist stiffness in combinations of FE and RUD.
      The purpose of this report is to present measurements of passive wrist stiffness
      throughout the space spanned by FE and RUD. Using a rehabilitation robot designed
      for the wrist and forearm, we measured the passive stiffness of the wrist joint
      in 10 subjects in FE, RUD, and combinations. For comparison, we measured the
      passive stiffness of the forearm (in pronation-supination), as well. Our
      measurements in pure FE and RUD agreed well with previous 1-DOF measurements. We
      have linearized the 2-DOF stiffness measurements and present them in the form of
      stiffness ellipses and as stiffness matrices useful for modeling wrist rotation
      dynamics. We found that passive wrist stiffness was anisotropic, with greater
      stiffness in RUD than in FE. We also found that passive wrist stiffness did not
      align with the anatomical axes of the wrist; the major and minor axes of the
      stiffness ellipse were rotated with respect to the FE and RUD axes by ~20 degrees
      . The direction of least stiffness was between ulnar flexion and radial
      extension, a direction used in many natural movements (known as the "dart
      thrower's motion"), suggesting that the nervous system may take advantage of the
      direction of least stiffness for common wrist rotations.

PMID- 22649210
TI  - Comparative effectiveness research: what is it and why do we need it in
      nephrology?
AB  - The USA leads other industrialized countries in health care spending but lags
      behind in terms of health outcomes. There has been growing interest in
      comparative effectiveness research (CER) as a means to identify best practices to
      create a more efficient and effective health care system. Two key concepts of CER
      are that it should (i) compare two or more alternative tests, therapies or
      procedures and (ii) be conducted in persons, clinical settings and conditions
      that are representative of the real world. The goal of CER is to provide evidence
      for clinicians, patients, policy makers and others to make informed decisions
      that will ultimately improve the overall health of specific subgroups and of the
      population as a whole. In this narrative review, we first describe the strengths
      and limitations of various types of studies that constitute CER, including
      randomized clinical trials, observational studies and systematic reviews,
      providing examples from the nephrology literature. Because of the concerns
      regarding confounding in observational CER, we also provide an overview of
      methods to reduce confounding in these types of studies. Finally, we will discuss
      why CER pertaining to kidney disease care needs to be a top priority in order to
      move our field from a largely opinion-based specialty to an evidence-based
      specialty.

PMID- 22649209
TI  - Electrophysiological characterization of Grueneberg ganglion olfactory neurons:
      spontaneous firing, sodium conductance, and hyperpolarization-activated currents.
AB  - Mammals rely on their acute olfactory sense for their survival. The most anterior
      olfactory subsystem in the nose, the Grueneberg ganglion (GG), plays a role in
      detecting alarm pheromone, cold, and urinary compounds. GG neurons respond
      homogeneously to these stimuli with increases in intracellular [Ca(2+)] or
      transcription of immediate-early genes. In this electrophysiological study, we
      used patch-clamp techniques to characterize the membrane properties of GG
      neurons. Our results offer evidence of functional heterogeneity in the GG. GG
      neurons fire spontaneously and independently in several stable patterns,
      including phasic and repetitive single-spike modes of discharge. Whole cell
      recordings demonstrated two distinct voltage-gated fast-inactivating Na(+)
      currents with different steady-state voltage dependencies and different
      sensitivities to tetrodotoxin. Hodgkin-Huxley simulations showed that these Na(+)
      currents confer dual mechanisms of action potential generation and contribute to
      different firing patterns. Additionally, GG neurons exhibited hyperpolarization
      activated inward currents that modulated spontaneous firing in vitro. Thus, in GG
      neurons, the heterogeneity of firing patterns is linked to the unusual repertoire
      of ionic currents. The membrane properties described here will aid the
      interpretation of chemosensory function in the GG.

PMID- 22649211
TI  - When should we commence dialysis? The story of a lingering problem and today's
      scene after the IDEAL study.
AB  - Over the last 15-20 years, there has been an increasing trend for dialysis to be
      commenced earlier in the development of chronic kidney disease (CKD). The drivers
      for initiation of dialysis at higher levels of renal function are complex but
      were primarily based on the assumption that by improving solute and water
      clearances with earlier dialysis, morbidity, mortality and quality of life would
      be improved. The Initiating Dialysis Early and Late (IDEAL) trial definitively
      demonstrated that elective earlier initiation of dialysis was not associated with
      improved clinical outcomes or quality of life. Indeed, no subset of patients was
      found to benefit from earlier dialysis. Observational data suggests that patients
      who commence dialysis with higher levels of renal function are more likely to
      have significant comorbidity that results in higher mortality rates compared to
      patients who remain clinically well and biochemically stable and are able to
      defer the initiation of dialysis till later in the course of CKD. However,
      patients who are able to defer dialysis should have appropriate access created so
      as to avoid the use of temporary catheters and to facilitate initiation using the
      preferred dialysis modality. Estimates of glomerular filtration rates in Stage 5
      CKD have been poorly validated and should not be used as the key determinant
      influencing the commencement of dialysis. The results of the IDEAL trial have
      influenced guidelines internationally and provide clinicians, patients and health
      care providers with important information to drive clinical decision making and
      rational service planning.

PMID- 22649213
TI  - Hippocampal abnormalities and memory deficits in Parkinson disease: a multimodal
      imaging study.
AB  - OBJECTIVES: Investigating in a case-control study whether the performance scores
      of a group of patients with Parkinson disease (PD) without dementia on tests of
      declarative memory could be predicted by hippocampal volume reduction (as
      assessed by automatic segmentation of cerebral magnetic resonance [MR] images) or
      by the rate of microstructural alterations (as evaluated by diffusion tensor
      analysis of MR images). METHOD: Twenty-five individuals with PD and 25 matched
      healthy control subjects underwent a 3-T MRI protocol with whole-brain T1
      weighted and diffusion tensor imaging and a neuropsychological assessment. Images
      were processed to obtain indices of macrostructural (volume) and microstructural
      (mean diffusivity [MD]) variation of bilateral hippocampi. Neuropsychological
      evaluation included tests of verbal memory (15-minute delayed recall of a 15-word
      list) and visuospatial memory (20-minute delayed reproduction of Rey complex
      figure). RESULTS: MD in the hippocampi of patients with PD was significantly
      increased with respect to that of the group of control subjects. Moreover,
      patients with high hippocampal MD values obtained low memory scores. In contrast,
      no difference emerged between patients with PD and healthy control subjects for
      hippocampal size, and no relationship could be found between hippocampal volumes
      and memory scores. CONCLUSIONS: These data confirm that the declarative memory
      impairment in patients with PD without dementia may be predicted by the rate of
      microstructural alterations in the hippocampal formation as detected by diffusion
      tensor imaging analysis.

PMID- 22649212
TI  - VHL regulates the effects of miR-23b on glioma survival and invasion via
      suppression of HIF-1alpha/VEGF and beta-catenin/Tcf-4 signaling.
AB  - Aberrant microRNA expression has been implicated in the development of human
      cancers. Here, we investigated the oncogenic significance and function of miR-23b
      in glioma. We identified that the expression of miR-23b was elevated in both
      glioma samples and glioma cells, indicated by real-time polymerase chain reaction
      analyses. Down-regulation of miR-23b triggered growth inhibition, induced
      apoptosis, and suppressed invasion of glioma in vitro. Luciferase assay and
      Western blot analysis revealed that VHL is a direct target of miR-23b. Restoring
      expression of VHL inhibited glioma proliferation and invasion. Mechanistic
      investigation revealed that miR-23b deletion decreased HIF-1alpha/VEGF expression
      and suppressed beta-catenin/Tcf-4 transcription activity by targeting VHL.
      Furthermore, expression of VHL was inversely correlated with miR-23b in glioma
      samples and was predictive of patient survival in a retrospective analysis.
      Therefore, we demonstrated that downregulation of miR-23b suppressed tumor
      survival through targeting VHL, leading to the inhibition of beta-catenin/Tcf-4
      and HIF-1alpha/VEGF signaling pathways.

PMID- 22649215
TI  - Progressive multifocal leukoencephalopathy in a patient with transitory
      lymphopenia.

PMID- 22649214
TI  - Progesterone vs placebo therapy for women with epilepsy: A randomized clinical
      trial.
AB  - OBJECTIVE: To assess progesterone treatment of intractable seizures in women with
      partial epilepsy. METHODS: This randomized, double-blind, placebo-controlled,
      phase III, multicenter, clinical trial compared the efficacy and safety of
      adjunctive cyclic natural progesterone therapy vs placebo treatment of
      intractable seizures in 294 subjects randomized 2:1 to progesterone or placebo,
      stratified by catamenial and noncatamenial status. It compared treatments on
      proportions of >=50% responders and changes in seizure frequency from 3 baseline
      to 3 treated menstrual cycles. RESULTS: There was no significant difference in
      proportions of responders between progesterone and placebo in the catamenial and
      noncatamenial strata. Prespecified secondary analysis showed that the level of
      perimenstrual seizure exacerbation (C1 level) was a significant predictor of
      responders for progesterone but not placebo. With increasing C1 levels,
      responders increased from 21% to 57% with progesterone vs 19% to 20% with
      placebo. Reductions in seizure frequency correlated with increasing C1 levels for
      progesterone but not placebo, progressing from 26% to 71% for progesterone vs 25%
      to 26% for placebo. A prespecified clinically important separation between
      progesterone and placebo responders (37.8% vs 11.1%; p = 0.037) was realized
      among 21.4% of women who had C1 level >=3. CONCLUSION: There was no difference in
      the primary outcome of >=50% responder rates between progesterone vs placebo for
      catamenial or noncatamenial groups. Post hoc findings suggest that the level of
      perimenstrual seizure exacerbation is a significant predictor of responder rate
      with progesterone and that progesterone may provide clinically important benefit
      for a subset of women with perimenstrually exacerbated seizures. CLASSIFICATION
      OF EVIDENCE: This study provides Class III evidence that cyclic progesterone is
      ineffective in women with intractable partial epilepsy. Post hoc analysis
      identified a subset of women with higher levels of perimenstrual seizure
      exacerbation that were responsive to treatment.

PMID- 22649216
TI  - Warfarin treatment and thrombolysis in acute stroke: are the procrastinators
      right?

PMID- 22649217
TI  - Subtherapeutic warfarin therapy entails an increased bleeding risk after stroke
      thrombolysis.
AB  - OBJECTIVE: To quantify the risk for bleeding complications after thrombolysis for
      ischemic stroke in patients on warfarin (international normalized ratio [INR] <=
      1.7) and to put these data into perspective with previous studies. METHODS: A
      total of 548 consecutive stroke patients receiving IV recombinant tissue
      plasminogen activator (rtPA) were prospectively evaluated and details about
      warfarin pretreatment were carefully recorded. Prothrombin time-based INR values
      were measured before thrombolysis and 6 and 24 hours thereafter. Intracranial
      hemorrhage occurring within 72 hours was assessed by CT examinations and defined
      according to National Institute of Neurological Disorders and Stroke criteria.
      Main outcome variables were symptomatic intracranial and major systemic
      bleedings. RESULTS: Of the 548 patients, 33 (6.0%) and 14 (2.6%) experienced
      symptomatic intracranial and major systemic bleedings, respectively. Patients
      taking warfarin until the day of or day before admission (n = 15, mean +/- SD INR
      1.21 +/- 0.32 vs 1.01 +/- 1.12, p = 0.030) faced an approximately 4-fold risk for
      intracranial hemorrhage (20.0% vs 5.6%, unadjusted odds ratio [OR] [95%
      confidence interval (CI)] 4.2 [1.1-15.7], p = 0.033). Findings were similar after
      adjustment for age, NIH Stroke Scale score, and diabetes (adjusted OR [95% CI]
      4.1 [1.0-16.1], p = 0.044) and when focusing on any major bleeding (intracranial
      or systemic) (unadjusted OR [95% CI] 4.1 [1.3-13.6], p = 0.019). Half of the
      patients with bleedings showed an INR rise above 1.7 6 hours after thrombolysis.
      A meta-analysis yielded confirmatory yet heterogeneous results (unadjusted OR
      [95% CI] derived from a random effects model, 2.31 [1.15-4.62], p = 0.018, I(2) =
      58% [11%-80%]). CONCLUSIONS: Our data suggest a statistically significant and
      clinically meaningful increase in the risk for symptomatic intracranial and major
      systemic bleedings among patients with stroke thrombolysis receiving warfarin up
      to the day of or day before stroke.

PMID- 22649218
TI  - An integer-based score to predict functional outcome in acute ischemic stroke:
      the ASTRAL score.
AB  - OBJECTIVE: To develop and validate a simple, integer-based score to predict
      functional outcome in acute ischemic stroke (AIS) using variables readily
      available after emergency room admission. METHODS: Logistic regression was
      performed in the derivation cohort of previously independent patients with AIS
      (Acute Stroke Registry and Analysis of Lausanne [ASTRAL]) to identify predictors
      of unfavorable outcome (3-month modified Rankin Scale score >2). An integer-based
      point-scoring system for each covariate of the fitted multivariate model was
      generated by their beta-coefficients; the overall score was calculated as the sum
      of the weighted scores. The model was validated internally using a 2-fold cross
      validation technique and externally in 2 independent cohorts (Athens and Vienna
      Stroke Registries). RESULTS: Age (A), severity of stroke (S) measured by
      admission NIH Stroke Scale score, stroke onset to admission time (T), range of
      visual fields (R), acute glucose (A), and level of consciousness (L) were
      identified as independent predictors of unfavorable outcome in 1,645 patients in
      ASTRAL. Their beta-coefficients were multiplied by 4 and rounded to the closest
      integer to generate the score. The area under the receiver operating
      characteristic curve (AUC) of the score in the ASTRAL cohort was 0.850. The score
      was well calibrated in the derivation (p = 0.43) and validation cohorts (0.22
      [Athens, n = 1,659] and 0.49 [Vienna, n = 653]). AUCs were 0.937 (Athens), 0.771
      (Vienna), and 0.902 (when pooled). An ASTRAL score of 31 indicates a 50%
      likelihood of unfavorable outcome. CONCLUSIONS: The ASTRAL score is a simple
      integer-based score to predict functional outcome using 6 readily available items
      at hospital admission. It performed well in double external validation and may be
      a useful tool for clinical practice and stroke research.

PMID- 22649219
TI  - Temporal trends in incidence and long-term case fatality of stroke among children
      from 1994 to 2007.
AB  - OBJECTIVE: To examine the trends in incidence and long-term case fatality of
      childhood stroke in New Jersey using a statewide administrative database for the
      years 1994-2007. METHODS: We assessed demographic and clinical information for
      children with stroke using the Myocardial Infarction Data Acquisition System
      (MIDAS) database. We ascertained deaths by matching MIDAS records to New Jersey
      Death Registration Files at 30 days, 1 year, and 5 years from the index stroke.
      RESULTS: During the 14-year study period, 715 children were hospitalized for a
      first time with stroke. Age-adjusted incidence of stroke demonstrated a
      significant quadratic trend in which the rates decreased from 1994 to a nadir at
      1999-2001 and increased thereafter (overall p for trend = 0.06 with quadratic
      term p = 0.02). Better treatment of sickle cell disease with transfusion therapy
      after year 1998 (p = 0.007) and improved diagnostic accuracy of MRI (p = 0.009)
      may partially explain these trends. Thirty-day, 1-year, and 5-year case fatality
      rates were 12.3%, 15.7%, and 17.5%, respectively. At all time periods, adjusted
      survival from hemorrhagic stroke was significantly lower than that from ischemic
      stroke (p = 0.0005). CONCLUSIONS: After an initial decrease, the incidence of
      pediatric stroke is rising. Children with hemorrhagic stroke had a 2 times higher
      risk of death than those with ischemic stroke. Whereas approximately 70% of all
      deaths occurred within the first month of hospitalization, an additional 5.2% of
      the initial study cohort died over the next 5 years.

PMID- 22649220
TI  - A new explanation for recessive myotonia congenita: exon deletions and
      duplications in CLCN1.
AB  - OBJECTIVE: To assess whether exon deletions or duplications in CLCN1 are
      associated with recessive myotonia congenita (MC). METHODS: We performed detailed
      clinical and electrophysiologic characterization in 60 patients with phenotypes
      consistent with MC. DNA sequencing of CLCN1 followed by multiplex ligation
      dependent probe amplification to screen for exon copy number variation was
      undertaken in all patients. RESULTS: Exon deletions or duplications in CLCN1 were
      identified in 6% of patients with MC. Half had heterozygous exonic
      rearrangements. The other 2 patients (50%), with severe disabling infantile onset
      myotonia, were identified with both a homozygous mutation, Pro744Thr, which
      functional electrophysiology studies suggested was nonpathogenic, and a
      triplication/homozygous duplication involving exons 8-14, suggesting an
      explanation for the severe phenotype. CONCLUSIONS: These data indicate that copy
      number variation in CLCN1 may be an important cause of recessive MC. Our
      observations suggest that it is important to check for exon deletions and
      duplications as part of the genetic analysis of patients with recessive MC,
      especially in patients in whom sequencing identifies no mutations or only a
      single recessive mutation. These results also indicate that additional, as yet
      unidentified, genetic mechanisms account for cases not currently explained by
      either CLCN1 point mutations or exonic deletions or duplications.

PMID- 22649221
TI  - Temporally selective firing of cortical and thalamic neurons during sleep and
      wakefulness.

PMID- 22649222
TI  - The diffusion tensor imaging toolbox.
AB  - During the past few years, The Journal of Neuroscience has published more than 30
      articles that describe investigations that used Diffusion Tensor Imaging (DTI)
      and related techniques as a primary observation method. This illustrates a
      growing interest in DTI within the basic and clinical neuroscience communities.
      This article summarizes DTI methodology in terms that can be immediately
      understood by the neuroscientist who has little previous exposure to DTI. It
      describes the fundamentals of water molecular diffusion coefficient measurement
      in brain tissue and illustrates how these fundamentals can be used to form vivid
      and useful depictions of white matter macroscopic and microscopic anatomy. It
      also describes current research applications and the technique's attributes and
      limitations. It is hoped that this article will help the readers of this Journal
      to more effectively evaluate neuroscience studies that use DTI.

PMID- 22649223
TI  - Gamma-band oscillations in the primary somatosensory cortex--a direct and
      obligatory correlate of subjective pain intensity.
AB  - Electroencephalographic gamma band oscillations (GBOs) induced over the human
      primary somatosensory cortex (SI) by nociceptive stimuli have been hypothesized
      to reflect cortical processing involved directly in pain perception, because
      their magnitude correlates with pain intensity. However, as stimuli perceived as
      more painful are also more salient, an alternative interpretation of this
      correlation is that GBOs reflect unspecific stimulus-triggered attentional
      processing. In fact, this is suggested by recent observations that other features
      of the electroencephalographic (EEG) response correlate with pain perception when
      stimuli are presented in isolation, but not when their saliency is reduced by
      repetition. Here, by delivering trains of three nociceptive stimuli at a constant
      1 s interval, and using different energies to elicit graded pain intensities, we
      demonstrate that GBOs recorded over SI always predict the subjective pain
      intensity, even when saliency is reduced by repetition. These results provide
      evidence for a close relationship between GBOs and the cortical activity
      subserving pain perception.

PMID- 22649224
TI  - Doublecortin (DCX) mediates endocytosis of neurofascin independently of
      microtubule binding.
AB  - Doublecortin on X chromosome (DCX) is one of two major genetic loci underlying
      human lissencephaly, a neurodevelopmental disorder with defects in neuronal
      migration and axon outgrowth. DCX is a microtubule-binding protein, and much work
      has focused on its microtubule-associated functions. DCX has other reported
      binding partners, including the cell adhesion molecule neurofascin, but the
      functional significance of the DCX-neurofascin interaction is not understood.
      Neurofascin localizes strongly to the axon initial segment in mature neurons,
      where it plays a role in assembling and maintaining other axon initial segment
      components. During development, neurofascin likely plays additional roles in axon
      guidance and in GABAergic synaptogenesis. We show here that DCX can modulate the
      surface distribution of neurofascin in developing cultured rat neurons and
      thereby the relative extent of accumulation between the axon initial segment and
      soma and dendrites. Mechanistically, DCX acts via increasing endocytosis of
      neurofascin from soma and dendrites. Surprisingly, DCX increases neurofascin
      endocytosis apparently independently of its microtubule-binding activity. We
      additionally show that the patient allele DCXG253D still binds microtubules but
      is deficient in promoting neurofascin endocytosis. We propose that DCX acts as an
      endocytic adaptor for neurofascin to fine-tune its surface distribution during
      neuronal development.

PMID- 22649226
TI  - Kinesin heavy chain function in Drosophila glial cells controls neuronal
      activity.
AB  - Kinesin heavy chain (Khc) is crucially required for axonal transport and khc
      mutants show axonal swellings and paralysis. Here, we demonstrate that in
      Drosophila khc is equally important in glial cells. Glial-specific downregulation
      of khc by RNA interference suppresses neuronal excitability and results in
      spastic flies. The specificity of the phenotype was verified by interspecies
      rescue experiments and further mutant analyses. Khc is mostly required in the
      subperineurial glia forming the blood-brain barrier. Following glial-specific
      knockdown, peripheral nerves are swollen with maldistributed mitochondria. To
      better understand khc function, we determined Khc-dependent Rab proteins in glia
      and present evidence that Neurexin IV, a well known blood-brain barrier
      constituent, is one of the relevant cargo proteins. Our work shows that the role
      of Khc for neuronal excitability must be considered in the light of its necessity
      for directed transport in glia.

PMID- 22649225
TI  - Caspase-6 activity in a BACHD mouse modulates steady-state levels of mutant
      huntingtin protein but is not necessary for production of a 586 amino acid
      proteolytic fragment.
AB  - Huntington's disease (HD) is caused by a mutation in the huntingtin (htt) gene
      encoding an expansion of glutamine repeats at the N terminus of the Htt protein.
      Proteolysis of Htt has been identified as a critical pathological event in HD
      models. In particular, it has been postulated that proteolysis of Htt at the
      putative caspase-6 cleavage site (at amino acid Asp-586) plays a critical role in
      disease progression and pathogenesis. However, whether caspase-6 is indeed the
      essential enzyme that cleaves Htt at this site in vivo has not been determined.
      To evaluate, we crossed the BACHD mouse model with a caspase-6 knock-out mouse
      (Casp6(-/-)). Western blot and immunocytochemistry confirmed the lack of caspase
      6 protein in Casp6(-/-) mice, regardless of HD genotype. We predicted the Casp6(
      /-) mouse would have reduced levels of caspase-6 Htt fragments and increased
      levels of full-length Htt protein. In contrast, we found a significant reduction
      of full-length mutant Htt (mHtt) and fragments in the striatum of BACHD Casp6(-/
      ) mice. Importantly, we detected the presence of Htt fragments consistent with
      cleavage at amino acid Asp-586 of Htt in the BACHD Casp6(-/-) mouse, indicating
      that caspase-6 activity cannot fully account for the generation of the Htt 586
      fragment in vivo. Our data are not consistent with the hypothesis that caspase-6
      activity is critical in generating a potentially toxic 586 aa Htt fragment in
      vivo. However, our studies do suggest a role for caspase-6 activity in clearance
      pathways for mHtt protein.

PMID- 22649227
TI  - Fgf-dependent glial cell bridges facilitate spinal cord regeneration in
      zebrafish.
AB  - Adult zebrafish show a remarkable capacity to regenerate their spinal column
      after injury, an ability that stands in stark contrast to the limited repair that
      occurs within the mammalian CNS post-injury. The reasons for this interspecies
      difference in regenerative capacity remain unclear. Here we demonstrate a novel
      role for Fgf signaling during glial cell morphogenesis in promoting axonal
      regeneration after spinal cord injury. Zebrafish glia are induced by Fgf
      signaling, to form an elongated bipolar morphology that forms a bridge between
      the two sides of the resected spinal cord, over which regenerating axons actively
      migrate. Loss of Fgf function inhibits formation of this "glial bridge" and
      prevents axon regeneration. Despite the poor potential for mammalian axonal
      regeneration, primate astrocytes activated by Fgf signaling adopt a similar
      morphology to that induced in zebrafish glia. This suggests that differential Fgf
      regulation, rather than intrinsic cell differences, underlie the distinct
      responses of mammalian and zebrafish glia to injury.

PMID- 22649228
TI  - Altered distribution of juxtaparanodal kv1.2 subunits mediates peripheral nerve
      hyperexcitability in type 2 diabetes mellitus.
AB  - Peripheral nerve hyperexcitability (PNH) is one of the distal peripheral
      neuropathy phenotypes often present in patients affected by type 2 diabetes
      mellitus (T2DM). Through in vivo and ex vivo electrophysiological recordings in
      db/db mice, a model of T2DM, we observed that, in addition to reduced nerve
      conduction velocity, db/db mice also develop PNH. By using pharmacological
      inhibitors, we demonstrated that the PNH is mediated by the decreased activity of
      K(v)1-channels. In agreement with these data, we observed that the diabetic
      condition led to a reduced presence of the K(v)1.2-subunits in juxtaparanodal
      regions of peripheral nerves in db/db mice and in nerve biopsies from T2DM
      patients. Together, these observations indicate that the T2DM condition leads to
      potassium channel-mediated PNH, thus identifying them as a potential drug target
      to treat some of the DPN related symptoms.

PMID- 22649229
TI  - Panglial gap junctional communication is essential for maintenance of myelin in
      the CNS.
AB  - In this study, we have investigated the contribution of oligodendrocytic
      connexin47 (Cx47) and astrocytic Cx30 to panglial gap junctional networks as well
      as myelin maintenance and function by deletion of both connexin coding DNAs in
      mice. Biocytin injections revealed complete disruption of oligodendrocyte-to
      astrocyte coupling in the white matter of 10- to 15-d-old Cx30/Cx47 double
      deficient mice, while oligodendrocyte-to-oligodendrocyte coupling was maintained.
      There were no quantitative differences regarding cellular networks in acute brain
      slices obtained from Cx30/Cx47 double-null mice and control littermates, probably
      caused by the upregulation of oligodendrocytic Cx32 in Cx30/Cx47 double-deficient
      mice. We observed early onset myelin pathology, and ~40% of Cx30/Cx47 double
      deficient animals died within 42 to 90 d after birth, accompanied by severe motor
      impairments. Histological and ultrastructural analyses revealed severe
      vacuolization and myelination defects in all white matter tracts of the CNS.
      Furthermore, Cx30/Cx47 double-deficient mice exhibited a decreased number of
      oligodendrocytes, severe astrogliosis, and microglial activation in white matter
      tracts. Although less affected concerning motor impairment, surviving double
      knock-out (KO) mice showed behavioral alterations in the open field and in the
      rotarod task. Vacuole formation and thinner myelin sheaths were evident also with
      adult surviving double-KO mice. Since interastrocytic coupling due to Cx43
      expression and interoligodendrocytic coupling because of Cx32 expression are
      still maintained, Cx30/Cx47 double-deficient mice demonstrate the functional role
      of both connexins for interastrocytic, interoligodendrocytic, and panglial
      coupling, and show that both connexins are required for maintenance of myelin.

PMID- 22649230
TI  - Enhanced synaptic integration of adult-born neurons in the olfactory bulb of
      lactating mothers.
AB  - One of the most dramatic events during the life of adult mammals is the
      transition into motherhood. This transition is accompanied by specific maternal
      behaviors, displayed by the mother, that ensure the survival and the well-being
      of her offspring. The execution of these behaviors is most likely accompanied by
      plastic changes in specific neuronal circuits, but these are still poorly
      defined. In this work, we studied the mammalian olfactory bulb (OB), which has
      been shown to be an essential brain region for maternal behaviors in mice. In the
      OB, we focused on adult-born neurons, which are continuously incorporated into
      the circuit during adulthood, thus providing a potential substrate for heightened
      plasticity after parturition. We analyzed the dynamics and morphological
      characteristics of adult-born granule cells (abGCs), innervating the OB of
      primiparous lactating mothers, shortly after parturition as well as in naive
      females. In vivo time-lapse imaging of abGCs revealed that dendritic spines were
      significantly more stable in lactating mothers compared with naive virgins. In
      contrast, spine stability of resident GCs remained unchanged after parturition.
      In addition, while spine size distribution of abGCs was approximately similar
      between mothers and naive virgins, the spine density of abGCs was lower in
      lactating mothers and the density of their presynaptic components was higher.
      These structural features are indicative of enhanced integration of adult-born
      neurons into the bulbar circuitry of lactating mothers. This enhanced integration
      may serve as a cellular mechanism, supporting changes in olfactory coding of new
      mothers during their first days following parturition.

PMID- 22649231
TI  - Surprise and error: common neuronal architecture for the processing of errors and
      novelty.
AB  - According to recent accounts, the processing of errors and generally infrequent,
      surprising (novel) events share a common neuroanatomical substrate. Direct
      empirical evidence for this common processing network in humans is, however,
      scarce. To test this hypothesis, we administered a hybrid error
      monitoring/novelty-oddball task in which the frequency of novel, surprising
      trials was dynamically matched to the frequency of errors. Using scalp
      electroencephalographic recordings and event-related functional magnetic
      resonance imaging (fMRI), we compared neural responses to errors with neural
      responses to novel events. In Experiment 1, independent component analysis of
      scalp ERP data revealed a common neural generator implicated in the generation of
      both the error-related negativity (ERN) and the novelty-related frontocentral N2.
      In Experiment 2, this pattern was confirmed by a conjunction analysis of event
      related fMRI, which showed significantly elevated BOLD activity following both
      types of trials in the posterior medial frontal cortex, including the anterior
      midcingulate cortex (aMCC), the neuronal generator of the ERN. Together, these
      findings provide direct evidence of a common neural system underlying the
      processing of errors and novel events. This appears to be at odds with prominent
      theories of the ERN and aMCC. In particular, the reinforcement learning theory of
      the ERN may need to be modified because it may not suffice as a fully integrative
      model of aMCC function. Whenever course and outcome of an action violates
      expectancies (not necessarily related to reward), the aMCC seems to be engaged in
      evaluating the necessity of behavioral adaptation.

PMID- 22649232
TI  - Functional organization of envelope-responsive neurons in early visual cortex:
      organization of carrier tuning properties.
AB  - It is well established that visual cortex neurons having similar selectivity for
      orientation, direction of motion, ocular dominance, and other properties of first
      order (luminance-defined) stimuli are clustered into a columnar organization.
      However, the cortical architecture of neuronal responses to second-order
      (contrast/texture-defined) stimuli is poorly understood. A useful second-order
      stimulus is a contrast envelope, consisting of a finely detailed pattern
      (carrier) whose contrast varies on a coarse spatial scale (envelope). In this
      study, we analyzed the cortical organization of carrier tuning properties of
      neurons, which responded to contrast-modulated stimuli. We examined whether
      neurons tuned to similar carrier properties are clustered spatially and whether
      such spatial clusters are arranged in columns. To address these questions, we
      recorded single-unit activity, multiunit activity, and local field potentials
      simultaneously from area 18 of anesthetized cats, using single-channel
      microelectrodes and multielectrode arrays. Our data showed that neurons tuned to
      similar carrier spatial frequency are distributed in a highly clustered manner;
      neurons tuned to similar carrier orientation are also significantly clustered.
      Neurons along linear arrays perpendicular to the brain surface always exhibited
      similar optimal carrier spatial frequency, indicating a columnar organization.
      Multi-pronged tetrode recordings indicated that the diameter of these columns is
      >=450 MUm. Optimal carrier orientation was also significantly clustered but with
      finer-grain organization and greater scatter. These results indicate a fine
      anatomical structure of cortical organization of second-order information
      processing and suggest that there are probably more maps in cat area 18 than
      previously believed.

PMID- 22649233
TI  - A critical role for protein tyrosine phosphatase nonreceptor type 5 in
      determining individual susceptibility to develop stress-related cognitive and
      morphological changes.
AB  - While stressful life events confer increased risk for the development of
      psychopathology, most individuals experiencing adversity maintain normal
      psychological functioning, suggesting that individual differences may influence
      the susceptibility to develop stress-related psychiatric disorders. However,
      little is known about what determines this difference between individuals at the
      molecular level. In the present study, we identify that protein tyrosine
      phosphatase nonreceptor type 5 (PTPN5) (also known as STEP) is a critical
      determinant of differences in individual susceptibility to develop stress-related
      cognitive and morphological changes in rats. Our data demonstrate that ablation
      of PTPN5 expression delays physiological recovery from stress and augments the
      development of stress-related cognitive and morphological changes, whereas
      overexpression of a constitutively active variant of PTPN5 enhances the
      individual's resilience to stress. Our data also reveal that reduced PTPN5
      expression prolongs the duration of extracellular signal-regulated kinase
      activation, leading to an elevation of Ca(V)1.2 channel expression and a recovery
      delay of K(V)4.2 channels from inactivation, which in turn heightens neuronal
      vulnerability to glutamate toxicity. Moreover, intraperitoneal injections of L
      type Ca(2+) channel blocker nifedipine after stress resulted in a significantly
      lower rate for developing stress-related cognitive and morphological changes seen
      in PTPN5 knockdown rats. Together, these results identify a novel role for PTPN5
      in mediating the development of stress-related cognitive and morphological
      changes and suggest that people with PTPN5 deficiency may have a greater
      susceptibility to capture the deleterious effects of stress.

PMID- 22649235
TI  - Is there a relationship between throbbing pain and arterial pulsations?
AB  - Pain can have a throbbing quality, especially when it is severe and disabling. It
      is widely held that this throbbing quality is a primary sensation of one's own
      arterial pulsations, arising directly from the activation of localized pain
      sensory neurons by closely apposed blood vessels. We examined this presumption
      more closely by simultaneously recording the subjective report of the throbbing
      rhythm and the arterial pulse in human subjects of either sex with throbbing
      dental pain-a prevalent condition whose pulsatile quality is widely regarded a
      primary sensation. Contrary to the generally accepted view, which would predict a
      direct correspondence between the two, we found that the throbbing rate (44 bpm
      +/- 3 SEM) was much slower than the arterial pulsation rate (73 bpm +/- 2 SEM, p
      < 0.001), and that the two rhythms exhibited no underlying synchrony. Moreover,
      the beat-to-beat variation in arterial and throbbing events observed distinct
      fractal properties, indicating that the physiological mechanisms underlying these
      rhythmic events are distinct. Confirmation of the generality of this observation
      in other pain conditions would support an alternative hypothesis that the
      throbbing quality is not a primary sensation but rather an emergent property, or
      perception, whose "pacemaker" lies within the CNS. Future studies leading to an
      improved understanding of the neurobiological basis of clinically relevant pain
      qualities, such as throbbing, will also enhance our ability to measure and
      therapeutically target severe and disabling pain.

PMID- 22649234
TI  - Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats.
AB  - Alcoholism is characterized by a compulsion to seek and ingest alcohol, loss of
      control over intake, and the emergence of a negative emotional state during
      abstinence. We hypothesized that sustained activation of neuroendocrine stress
      systems (e.g., corticosteroid release via the hypothalamic-pituitary-adrenal
      axis) by alcohol intoxication and withdrawal and consequent alterations in
      glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation drive
      compulsive alcohol drinking. Our results showed that rats exposed to alcohol
      vapor to the point of dependence displayed increased alcohol intake, compulsive
      drinking measured by progressive-ratio responding, and persistent alcohol
      consumption despite punishment, assessed by adding quinine to the alcohol
      solution, compared with control rats that were not exposed to alcohol vapor. No
      group differences were observed in the self-administration of saccharin-sweetened
      water. Acute alcohol withdrawal was accompanied by downregulated GR mRNA in
      various stress/reward-related brain regions [i.e., prefrontal cortex, nucleus
      accumbens (NAc), and bed nucleus of the stria terminalis (BNST)], whereas
      protracted alcohol abstinence was accompanied by upregulated GR mRNA in the NAc
      core, ventral BNST, and central nucleus of the amygdala. No significant
      alterations in MR mRNA levels were found. Chronic GR antagonism with mifepristone
      (RU38486) prevented the escalation of alcohol intake and compulsive responding
      induced by chronic, intermittent alcohol vapor exposure. Chronic treatment with
      mifepristone also blocked escalated alcohol drinking and compulsive responding
      during protracted abstinence. Thus, the GR system appears to be involved in the
      development of alcohol dependence and may represent a potential pharmacological
      target for the treatment of alcoholism.

PMID- 22649236
TI  - Serum response factor and cAMP response element binding protein are both required
      for cocaine induction of DeltaFosB.
AB  - The molecular mechanism underlying induction by cocaine of DeltaFosB, a
      transcription factor important for addiction, remains unknown. Here, we
      demonstrate a necessary role for two transcription factors, cAMP response element
      binding protein (CREB) and serum response factor (SRF), in mediating this
      induction within the mouse nucleus accumbens (NAc), a key brain reward region.
      CREB and SRF are both activated in NAc by cocaine and bind to the fosB gene
      promoter. Using viral-mediated Cre recombinase expression in the NAc of single-
      or double-floxed mice, we show that deletion of both transcription factors from
      this brain region completely blocks cocaine induction of DeltaFosB in NAc,
      whereas deletion of either factor alone has no effect. Furthermore, deletion of
      both SRF and CREB from NAc renders animals less sensitive to the rewarding
      effects of moderate doses of cocaine when tested in the conditioned place
      preference (CPP) procedure and also blocks locomotor sensitization to higher
      doses of cocaine. Deletion of CREB alone has the opposite effect and enhances
      both cocaine CPP and locomotor sensitization. In contrast to DeltaFosB induction
      by cocaine, DeltaFosB induction in NAc by chronic social stress, which we have
      shown previously requires activation of SRF, is unaffected by the deletion of
      CREB alone. These surprising findings demonstrate the involvement of distinct
      transcriptional mechanisms in mediating DeltaFosB induction within this same
      brain region by cocaine versus stress. Our results also establish a complex mode
      of regulation of DeltaFosB induction in response to cocaine, which requires the
      concerted activities of both SRF and CREB.

PMID- 22649237
TI  - Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and
      promotes presynaptic accumulation of alpha-synuclein and LRRK2 in the brain.
AB  - Parkinson's disease (PD) is characterized pathologically by the formation of
      ubiquitin and alpha-synuclein (alpha-syn)-containing inclusions (Lewy bodies),
      dystrophic dopamine (DA) terminals, and degeneration of midbrain DA neurons. The
      precise molecular mechanisms underlying these pathological features remain
      elusive. Accumulating evidence has implicated dysfunctional autophagy, the cell
      self-digestion and neuroprotective pathway, as one of the pathogenic systems
      contributing to the development of idiopathic PD. Here we characterize autophagy
      deficient mouse models and provide in vivo evidence for the potential role that
      impaired autophagy plays in pathogenesis associated with PD. Cell-specific
      deletion of essential autophagy gene Atg7 in midbrain DA neurons causes delayed
      neurodegeneration, accompanied by late-onset locomotor deficits. In contrast,
      Atg7-deficient DA neurons in the midbrain exhibit early dendritic and axonal
      dystrophy, reduced striatal dopamine content, and the formation of somatic and
      dendritic ubiquitinated inclusions in DA neurons. Furthermore, whole-brain
      specific loss of Atg7 leads to presynaptic accumulation of alpha-syn and LRRK2
      proteins, which are encoded by two autosomal dominantly inherited PD-related
      genes. Our results suggest that disrupted autophagy may be associated with
      enhanced levels of endogenous alpha-syn and LRRK2 proteins in vivo. Our findings
      implicate dysfunctional autophagy as one of the failing cellular mechanisms
      involved in the pathogenesis of idiopathic PD.

PMID- 22649238
TI  - Similar effects of feature-based attention on motion perception and pursuit eye
      movements at different levels of awareness.
AB  - Feature-based attention enhances visual processing and improves perception, even
      for visual features that we are not aware of. Does feature-based attention also
      modulate motor behavior in response to visual information that does or does not
      reach awareness? Here we compare the effect of feature-based attention on motion
      perception and smooth-pursuit eye movements in response to moving dichoptic
      plaids--stimuli composed of two orthogonally drifting gratings, presented
      separately to each eye--in human observers. Monocular adaptation to one grating
      before the presentation of both gratings renders the adapted grating perceptually
      weaker than the unadapted grating and decreases the level of awareness. Feature
      based attention was directed to either the adapted or the unadapted grating's
      motion direction or to both (neutral condition). We show that observers were
      better at detecting a speed change in the attended than the unattended motion
      direction, indicating that they had successfully attended to one grating. Speed
      change detection was also better when the change occurred in the unadapted than
      the adapted grating, indicating that the adapted grating was perceptually weaker.
      In neutral conditions, perception and pursuit in response to plaid motion were
      dissociated: While perception followed one grating's motion direction almost
      exclusively (component motion), the eyes tracked the average of both gratings
      (pattern motion). In attention conditions, perception and pursuit were shifted
      toward the attended component. These results suggest that attention affects
      perception and pursuit similarly even though only the former reflects awareness.
      The eyes can track an attended feature even if observers do not perceive it.

PMID- 22649239
TI  - The role of a voltage-dependent Ca2+ channel intracellular linker: a structure
      function analysis.
AB  - Voltage-dependent calcium channels (VDCCs) allow the passage of Ca(2+) ions
      through cellular membranes in response to membrane depolarization. The channel
      pore-forming subunit, alpha1, and a regulatory subunit (Ca(V)beta) form a high
      affinity complex where Ca(V)beta binds to a alpha1 interacting domain in the
      intracellular linker between alpha1 membrane domains I and II (I-II linker). We
      determined crystal structures of Ca(V)beta2 functional core in complex with the
      Ca(V)1.2 and Ca(V)2.2 I-II linkers to a resolution of 1.95 and 2.0 A,
      respectively. Structural differences between the highly conserved linkers,
      important for coupling Ca(V)beta to the channel pore, guided mechanistic
      functional studies. Electrophysiological measurements point to the importance of
      differing linker structure in both Ca(V)1 and 2 subtypes with mutations affecting
      both voltage- and calcium-dependent inactivation and voltage dependence of
      activation. These linker effects persist in the absence of Ca(V)beta, pointing to
      the intrinsic role of the linker in VDCC function and suggesting that I-II linker
      structure can serve as a brake during inactivation.

PMID- 22649240
TI  - Intrinsic network connectivity reflects consistency of synesthetic experiences.
AB  - Studying cognitive processes underlying synesthesia, a condition in which
      stimulation of one sensory modality automatically leads to abnormal additional
      sensory perception, allows insights into the neural mechanisms of normal and
      abnormal cross-modal sensory processing. Consistent with the notion that
      synesthesia results from hyperconnectivity, functional connectivity analysis
      (adopting independent component analysis and seed-based correlation analysis) of
      resting-state functional magnetic resonance imaging data of 12 grapheme-color
      synesthetes and 12 nonsynesthetic control subjects revealed, in addition to
      increased intranetwork connectivity, both a global and a specific (medial and
      lateral visual networks to a right frontoparietal network) increase of intrinsic
      internetwork connectivity in grapheme-color synesthesia. Moreover, this increased
      intrinsic network connectivity reflected the strength of synesthetic experiences.
      These findings constitute the first direct evidence of increased functional
      network connectivity in synesthesia. In addition to this significant contribution
      to the understanding of the neural mechanisms of synesthesia, our results have
      important general implications. In combination with data derived from clinical
      populations, our data strongly suggest that altered differences in intrinsic
      network connectivity are directly related to the phenomenology of human
      experiences.

PMID- 22649241
TI  - Thrombin activity associated with neuronal damage during acute focal ischemia.
AB  - Mechanisms of ischemic neuronal and vascular injury remain obscure. Here we test
      the hypothesis that thrombin, a blood-borne coagulation factor, contributes to
      neurovascular injury during acute focal ischemia. Stroke was induced in adult
      Sprague Dawley rats by occluding the middle cerebral artery. Intra-arterial
      thrombin infusion during ischemia significantly increased vascular disruption and
      cellular injury. Intravenous infusion of argatroban, a direct thrombin inhibitor,
      alleviated neurovascular injury. Immunostaining showed thrombin on neurons in the
      ischemic core. Using an activatable cell-penetrating peptide engineered to detect
      thrombin activity, we discovered that thrombin proteolytic activity was
      specifically associated with neuronal damage during ischemia. Protease activated
      receptor-1, the presumptive thrombin receptor, appeared to mediate ischemic
      neurovascular injury. Furthermore, rats receiving thrombin during ischemia showed
      cognitive deficit, whereas rats receiving argatroban retained intact learning and
      memory. These results suggest a potential role for thrombin contributing to
      neurovascular injury and several potential avenues for neuroprotection.

PMID- 22649242
TI  - Critical time window of neuronal cholesterol synthesis during neurite outgrowth.
AB  - Cholesterol is an essential membrane component enriched in plasma membranes,
      growth cones, and synapses. The brain normally synthesizes all cholesterol
      locally, but the contribution of individual cell types to brain cholesterol
      metabolism is unknown. To investigate whether cortical projection neurons in vivo
      essentially require cholesterol biosynthesis and which cell types support
      neurons, we have conditionally ablated the cholesterol biosynthesis in these
      neurons in mice either embryonically or postnatally. We found that cortical
      projection neurons synthesize cholesterol during their entire lifetime. At all
      stages, they can also benefit from glial support. Adult neurons that lack
      cholesterol biosynthesis are mainly supported by astrocytes such that their
      functional integrity is preserved. In contrast, microglial cells support young
      neurons. However, compensatory efforts of microglia are only transient leading to
      layer-specific neuronal death and the reduction of cortical projections. Hence,
      during the phase of maximal membrane growth and maximal cholesterol demand,
      neuronal cholesterol biosynthesis is indispensable. Analysis of primary neurons
      revealed that neurons tolerate only slight alteration in the cholesterol content
      and plasma membrane tension. This quality control allows neurons to differentiate
      normally and adjusts the extent of neurite outgrowth, the number of functional
      growth cones and synapses to the available cholesterol. This study highlights
      both the flexibility and the limits of horizontal cholesterol transfer in vivo
      and may have implications for the understanding of neurodegenerative diseases.

PMID- 22649243
TI  - Response of dorsomedial prefrontal cortex predicts altruistic behavior.
AB  - Human beings have an unusual proclivity for altruistic behavior, and recent
      commentators have suggested that these prosocial tendencies arise from our unique
      capacity to understand the minds of others (i.e., to mentalize). The current
      studies test this hypothesis by examining the relation between altruistic
      behavior and the reflexive engagement of a neural system reliably associated with
      mentalizing. Results indicated that activity in the dorsomedial prefrontal cortex
      -a region consistently involved in understanding others' mental states--predicts
      both monetary donations to others and time spent helping others. These findings
      address long-standing questions about the proximate source of human altruism by
      suggesting that prosocial behavior results, in part, from our broader tendency
      for social-cognitive thought.

PMID- 22649245
TI  - Prefrontal neurons represent winning and losing during competitive video shooting
      games between monkeys.
AB  - Humans and animals must work to support their survival and reproductive needs.
      Because resources are limited in the natural environment, competition is
      inevitable, and competing successfully is vitally important. However, the
      neuronal mechanisms of competitive behavior are poorly studied. We examined
      whether neurons in the lateral prefrontal cortex (LPFC) showed response
      sensitivity related to a competitive game. In this study, monkeys played a video
      shooting game, either competing with another monkey or the computer, or playing
      alone without a rival. Monkeys performed more quickly and more accurately in the
      competitive than in the noncompetitive games, indicating that they were more
      motivated in the competitive than in the noncompetitive games. LPFC neurons
      showed differential activity between the competitive and noncompetitive games
      showing winning- and losing-related activity. Furthermore, activities of
      prefrontal neurons differed depending on whether the competition was between
      monkeys or between the monkey and the computer. These results indicate that LPFC
      neurons may play an important role in monitoring the outcome of competition and
      enabling animals to adapt their behavior to increase their chances of obtaining a
      reward in a socially interactive environment.

PMID- 22649244
TI  - Glutamatergic synapse formation is promoted by alpha7-containing nicotinic
      acetylcholine receptors.
AB  - Glutamate is the primary excitatory transmitter in adult brain, acting through
      synapses on dendritic spines and shafts. Early in development, however, when
      glutamatergic synapses are only beginning to form, nicotinic cholinergic
      excitation is already widespread; it is mediated by acetylcholine activating
      nicotinic acetylcholine receptors (nAChRs) that generate waves of activity across
      brain regions. A major class of nAChRs contributing at this time is a species
      containing alpha7 subunits (alpha7-nAChRs). These receptors are highly permeable
      to calcium, influence a variety of calcium-dependent events, and are diversely
      distributed throughout the developing CNS. Here we show that alpha7-nAChRs
      unexpectedly promote formation of glutamatergic synapses during development. The
      dependence on alpha7-nAChRs becomes clear when comparing wild-type (WT) mice with
      mice constitutively lacking the alpha7-nAChR gene. Ultrastructural analysis,
      immunostaining, and patch-clamp recording all reveal synaptic deficits when
      alpha7-nAChR input is absent. Similarly, nicotinic activation of alpha7-nAChRs in
      WT organotypic culture, as well as cell culture, increases the number of
      glutamatergic synapses. RNA interference demonstrates that the alpha7-nAChRs must
      be expressed in the neuron being innervated for normal innervation to occur.
      Moreover, the deficits persist throughout the developmental period of major de
      novo synapse formation and are still fully apparent in the adult. GABAergic
      synapses, in contrast, are undiminished in number under such conditions. As a
      result, mice lacking alpha7-nAChRs have an altered balance in the
      excitatory/inhibitory input they receive. This ratio represents a fundamental
      feature of neural networks and shows for the first time that endogenous nicotinic
      cholinergic signaling plays a key role in network construction.

PMID- 22649247
TI  - Object ensemble processing in human anterior-medial ventral visual cortex.
AB  - Our visual system can extract summary statistics from large collections of
      similar objects without forming detailed representations of the individual
      objects in the ensemble. Such object ensemble representation is adaptive and
      allows us to overcome the capacity limitation associated with representing
      specific objects. Surprisingly, little is known about the neural mechanisms
      supporting such object ensemble representation. Here we showed human observers
      identical photographs of the same object ensemble, different photographs
      depicting the same ensemble, or different photographs depicting different
      ensembles. We observed fMRI adaptation in anterior-medial ventral visual cortex
      whenever object ensemble statistics repeated, even when local image features
      differed across photographs. Interestingly, such object ensemble processing is
      closely related to texture and scene processing in the brain. In contrast, the
      lateral occipital area, a region involved in object-shape processing, showed
      adaptation only when identical photographs were repeated. These results provide
      the first step toward understanding the neural underpinnings of real-world object
      ensemble representation.

PMID- 22649246
TI  - Filamin a regulates neural progenitor proliferation and cortical size through
      Wee1-dependent Cdk1 phosphorylation.
AB  - Cytoskeleton-associated proteins play key roles not only in regulating cell
      morphology and migration but also in proliferation. Mutations in the cytoskeleton
      associated gene filamin A (FlnA) cause the human disorder periventricular
      heterotopia (PH). PH is a disorder of neural stem cell development that is
      characterized by disruption of progenitors along the ventricular epithelium and
      subsequent formation of ectopic neuronal nodules. FlnA-dependent regulation of
      cytoskeletal dynamics is thought to direct neural progenitor migration and
      proliferation. Here we show that embryonic FlnA-null mice exhibited a reduction
      in brain size and decline in neural progenitor numbers over time. The drop in the
      progenitor population was not attributable to cell death or changes in premature
      differentiation, but to prolonged cell cycle duration. Suppression of FlnA led to
      prolongation of the entire cell cycle length, principally in M phase. FlnA loss
      impaired degradation of cyclin B1-related proteins, thereby delaying the onset
      and progression through mitosis. We found that the cdk1 kinase Wee1 bound FlnA,
      demonstrated increased expression levels after loss of FlnA function, and was
      associated with increased phosphorylation of cdk1. Phosphorylation of cdk1
      inhibited activation of the anaphase promoting complex degradation system, which
      was responsible for cyclin B1 degradation and progression through mitosis.
      Collectively, our results demonstrate a molecular mechanism whereby FlnA loss
      impaired G2 to M phase entry, leading to cell cycle prolongation, compromised
      neural progenitor proliferation, and reduced brain size.

PMID- 22649248
TI  - Nerve growth factor in the hippocamposeptal system: evidence for activity
      dependent anterograde delivery and modulation of synaptic activity.
AB  - Neurotrophins have been implicated in regulating neuronal differentiation,
      promoting neuronal survival, and modulating synaptic efficacy and plasticity. The
      prevailing view is that, depending on the target and mode of action, most
      neurotrophins can be trafficked and released either anterogradely or retrogradely
      in an activity-dependent manner. However, the prototypic neurotrophin, nerve
      growth factor (NGF), is not thought to be anterogradely delivered. Here we
      provide the neuroanatomical substrate for an anterograde hippocamposeptal
      transport of NGF by demonstrating its presence in mouse hippocampal GABAergic
      neurons and in their hippocamposeptal axons that ramify densely and abut neurons
      in the medial septum/diagonal band of Broca (MS/DB). We also demonstrate an
      activity-dependent increase in septal NGF levels that is dependent on the pattern
      of intrahippocampal stimulation. In addition, we show that acute exposure to NGF,
      via activation of TrkA, attenuates GABA(A) receptor-mediated inhibitory synaptic
      currents and reduces sensitivity to exogenously applied GABA. These acute actions
      of NGF display cell type and functional selectivity insofar as (1) they were
      found in cholinergic, but not GABAergic, MS/DB neurons, and (2) glutamate
      mediated excitatory synaptic activity as well as AMPA-activated current responses
      were unaffected. Our results advocate a novel anterograde, TrkA-mediated NGF
      signaling in the CNS.

PMID- 22649249
TI  - Homologous mechanisms of visuospatial working memory maintenance in macaque and
      human: properties and sources.
AB  - Although areas of frontal cortex are thought to be critical for maintaining
      information in visuospatial working memory, the event-related potential (ERP)
      index of maintenance is found over posterior cortex in humans. In the present
      study, we reconcile these seemingly contradictory findings. Here, we show that
      macaque monkeys and humans exhibit the same posterior ERP signature of working
      memory maintenance that predicts the precision of the memory-based behavioral
      responses. In addition, we show that the specific pattern of rhythmic
      oscillations in the alpha band, recently demonstrated to underlie the human
      visual working memory ERP component, is also present in monkeys. Next, we
      concurrently recorded intracranial local field potentials from two prefrontal and
      another frontal cortical area to determine their contribution to the surface
      potential indexing maintenance. The local fields in the two prefrontal areas, but
      not the cortex immediately posterior, exhibited amplitude modulations, timing,
      and relationships to behavior indicating that they contribute to the generation
      of the surface ERP component measured from the distal posterior electrodes.
      Rhythmic neural activity in the theta and gamma bands during maintenance provided
      converging support for the engagement of the same brain regions. These findings
      demonstrate that nonhuman primates have homologous electrophysiological
      signatures of visuospatial working memory to those of humans and that a
      distributed neural network, including frontal areas, underlies the posterior ERP
      index of visuospatial working memory maintenance.

PMID- 22649250
TI  - Optimal deployment of attentional gain during fine discriminations.
AB  - Most models assume that top-down attention enhances the gain of sensory neurons
      tuned to behaviorally relevant stimuli (on-target gain). However, theoretical
      work suggests that when targets and distracters are highly similar, attention
      should enhance the gain of neurons that are tuned away from the target, because
      these neurons better discriminate neighboring features (off-target gain). While
      it is established that off-target neurons support difficult fine discriminations,
      it is unclear if top-down attentional gain can be optimally applied to
      informative off-target sensory neurons or if gain is always applied to on-target
      neurons, regardless of task demands. To test the optimality of attentional gain
      in human visual cortex, we used functional magnetic resonance imaging and an
      encoding model to estimate the response profile across a set of hypothetical
      orientation-selective channels during a difficult discrimination task. The
      results suggest that top-down attention can adaptively modulate off-target neural
      populations, but only when the discriminanda are precisely specified in advance.
      Furthermore, logistic regression revealed that activation levels in off-target
      orientation channels predicted behavioral accuracy on a trial-by-trial basis.
      Overall, these data suggest that attention does not only increase the gain of
      sensory-evoked responses, but may bias population response profiles in an optimal
      manner that respects both the tuning properties of sensory neurons and the
      physical characteristics of the stimulus array.

PMID- 22649251
TI  - Soluble adenylyl cyclase activity is necessary for retinal ganglion cell survival
      and axon growth.
AB  - cAMP is a critical second messenger mediating activity-dependent neuronal
      survival and neurite growth. We investigated the expression and function of the
      soluble adenylyl cyclase (sAC, ADCY10) in CNS retinal ganglion cells (RGCs). We
      found sAC protein expressed in multiple RGC compartments including the nucleus,
      cytoplasm and axons. sAC activation increased cAMP above the level seen with
      transmembrane adenylate cyclase (tmAC) activation. Electrical activity and
      bicarbonate, both physiologic sAC activators, significantly increased survival
      and axon growth, whereas pharmacologic or siRNA-mediated sAC inhibition
      dramatically decreased RGC survival and axon growth in vitro, and survival in
      vivo. Conversely, RGC survival and axon growth were unaltered in RGCs from
      AC1/AC8 double knock-out mice or after specifically inhibiting tmACs. These data
      identify a novel sAC-mediated cAMP signaling pathway regulating RGC survival and
      axon growth, and suggest new neuroprotective or regenerative strategies based on
      sAC modulation.

PMID- 22649252
TI  - Toll/interleukin-1 receptor domain-containing adapter inducing interferon-beta
      mediates microglial phagocytosis of degenerating axons.
AB  - Following CNS injury, microglial phagocytosis of damaged endogenous tissue is
      thought to play an important role in recovery and regeneration. Previous work has
      focused on delineating mechanisms of clearance of neurons and myelin. Little,
      however, is known of the mechanisms underlying phagocytosis of axon debris. We
      have developed a novel microfluidic platform that enables coculture of microglia
      with bundles of CNS axons to investigate mechanisms of microglial phagocytosis of
      axons. Using this platform, we find that axon degeneration results in the
      induction of type-1 interferon genes within microglia. Pharmacologic and genetic
      disruption of Toll/interleukin-1 receptor domain-containing adapter inducing
      interferon-beta (TRIF), a Toll-like receptor adapter protein, blocks induction of
      the interferon response and inhibits microglial phagocytosis of axon debris in
      vitro. In vivo, microglial phagocytosis of axons following dorsal root axotomy is
      impaired in mice in which TRIF has been genetically deleted. Furthermore, we
      identify the p38 mitogen-activated protein kinase (MAPK) cascade as a signaling
      pathway downstream of TRIF following axon degeneration and find that inhibition
      of p38 MAPK by SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4
      pyridyl)-1H-imidazole) also blocked clearance of axon debris. Finally, we find
      that TRIF-dependent microglial clearance of unmyelinated axon debris facilitates
      axon outgrowth. Overall, we provide evidence that TRIF-mediated signaling plays
      an unexpected role in axonal debris clearance by microglia, thereby facilitating
      a more permissive environment for axonal outgrowth. Our study has significant
      implications for the development of novel regenerative and restorative strategies
      for the many traumatic, neuroinflammatory, and neurodegenerative conditions
      characterized by CNS axon degeneration.

PMID- 22649253
TI  - Effects of early-life abuse differ across development: infant social behavior
      deficits are followed by adolescent depressive-like behaviors mediated by the
      amygdala.
AB  - Abuse during early life, especially from the caregiver, increases vulnerability
      to develop later-life psychopathologies such as depression. Although signs of
      depression are typically not expressed until later life, signs of dysfunctional
      social behavior have been found earlier. How infant abuse alters the trajectory
      of brain development to produce pathways to pathology is not completely
      understood. Here we address this question using two different but complementary
      rat models of early-life abuse from postnatal day 8 (P8) to P12: a naturalistic
      paradigm, where the mother is provided with insufficient bedding for nest
      building; and a more controlled paradigm, where infants undergo olfactory
      classical conditioning. Amygdala neural assessment (c-Fos), as well as social
      behavior and forced swim tests were performed at preweaning (P20) and adolescence
      (P45). Our results show that both models of early-life abuse induce deficits in
      social behavior, even during the preweaning period; however, depressive-like
      behaviors were observed only during adolescence. Adolescent depressive-like
      behavior corresponds with an increase in amygdala neural activity in response to
      forced swim test. A causal relationship between the amygdala and depressive-like
      behavior was suggested through amygdala temporary deactivation (muscimol
      infusions), which rescued the depressive-like behavior in the forced swim test.
      Our results indicate that social behavior deficits in infancy could serve as an
      early marker for later psychopathology. Moreover, the implication of the amygdala
      in the ontogeny of depressive-like behaviors in infant abused animals is an
      important step toward understanding the underlying mechanisms of later-life
      mental disease associated with early-life abuse.

PMID- 22649254
TI  - Autophagy and cell growth--the yin and yang of nutrient responses.
AB  - As a response to nutrient deprivation and other cell stresses, autophagy is often
      induced in the context of reduced or arrested cell growth. A plethora of
      signaling molecules and pathways have been shown to have opposing effects on cell
      growth and autophagy, and results of recent functional screens on a genomic scale
      support the idea that these processes might represent mutually exclusive cell
      fates. Understanding the ways in which autophagy and cell growth relate to one
      another is becoming increasingly important, as new roles for autophagy in
      tumorigenesis and other growth-related phenomena are uncovered. This Commentary
      highlights recent findings that link autophagy and cell growth, and explores the
      mechanisms underlying these connections and their implications for cell
      physiology and survival. Autophagy and cell growth can inhibit one another
      through a variety of direct and indirect mechanisms, and can be independently
      regulated by common signaling pathways. The central role of the mammalian target
      of rapamycin (mTOR) pathway in regulating both autophagy and cell growth
      exemplifies one such mechanism. In addition, mTOR-independent signaling and other
      more direct connections between autophagy and cell growth will also be discussed.

PMID- 22649255
TI  - Folate network genetic variation predicts cardiovascular disease risk in non
      Hispanic white males.
AB  - Genes functioning in folate-mediated 1-carbon metabolism are hypothesized to play
      a role in cardiovascular disease (CVD) risk beyond the current narrow focus on
      the MTHFR 677 C->T (rs1801133) polymorphism. Using a cohort study design, we
      investigated whether sequence variants in the network of folate-related genes,
      particularly in genes encoding proteins related to SHMT1, predict CVD risk in
      1131 men from the Normative Aging Study. A total of 330 single nucleotide
      polymorphisms (SNPs) in 52 genes, selected for function and gene coverage, were
      assayed on the Illumina GoldenGate platform. Age- and smoking-adjusted genotype
      phenotype associations were estimated in regression models. Using a nominal P <=
      5.00 * 10(-3) significance threshold, 8 SNPs were associated with CVD risk in
      single locus analyses. Using a false discovery rate (FDR) threshold (P-adjusted
      <=1.00 * 10(-1)), a SNP in the GGH gene remained associated with reduced CVD
      risk, with a stronger association in early onset CVD cases (<55 y). A gene *
      folate interaction (MAT2B) and 2 gene * vitamin B-12 interactions (BHMT,
      SLC25A32) reached the FDR P-adjusted <=2.00 * 10(-1) threshold. Three biological
      hypotheses related to SHMT1 were explored and significant gene * gene
      interactions were identified for TYMS by UBE2N, FTH1 by CELF1, and TYMS by MTHFR.
      Variations in genes other than MTHFR and those directly involved in homocysteine
      metabolism are associated with CVD risk in non-Hispanic white males. This work
      supports a role for SHMT1-related genes and nuclear folate metabolism, including
      the thymidylate biosynthesis pathway, in mediating CVD risk.

PMID- 22649256
TI  - Altered carcinogenesis and proteome in mammary glands of rats after prepubertal
      exposures to the hormonally active chemicals bisphenol a and genistein.
AB  - Through our diet, we are exposed to numerous natural and man-made chemicals,
      including polyphenols with hormone-like properties. The most abundant hormonally
      active polyphenols are characterized as weak estrogens. These chemicals are
      hypothesized to interfere with signaling pathways involved in important diseases
      such as breast cancer, which in most cases is initially estrogen dependent. Two
      such chemicals are bisphenol A (BPA), a plasticizer, and genistein, a component
      of soy. In spite of both possessing estrogenic properties, BPA and genistein
      yield different health outcomes. The exposure of rats during the prepubertal
      period to BPA increases the susceptibility of adult animals for mammary cancer
      development, whereas genistein decreases this susceptibility in a chemically
      induced model. Because both BPA and genistein possess estrogenic properties, it
      is certainly plausible that additional mechanisms are affected by these
      chemicals. Hence, it was our goal to investigate at the protein level how
      exposure to these 2 chemicals can contribute to mammary cancer causation as
      opposed to cancer chemoprevention. Using 2-dimensional gel electrophoresis
      followed by MS analysis, we identified differentially regulated proteins from the
      mammary glands of rats prepubertally exposed to BPA and genistein. Following
      protein identification, we used immunoblotting techniques to validate the
      identity and regulation of these proteins and to identify downstream signaling
      proteins. Our studies highlight the importance of proteomics technology in
      elucidating signaling pathways altered by exposure to hormonally active chemicals
      and its potential value in identifying biomarkers for mammary cancer.

PMID- 22649257
TI  - Monomer and linkage type of galacto-oligosaccharides affect their resistance to
      ileal digestion and prebiotic properties in rats.
AB  - A detailed study was performed to compare the in vivo ileal digestibility and
      modulatory effects in fecal microbiota of novel galacto-oligosaccharides (GOS)
      derived from lactulose [GOS-Lu; degree of polymerization (DP) >=2, 14.0%
      trisaccharides] and commercial GOS derived from lactose (GOS-La; DP >=3, 35.1%
      trisaccharides) in growing rats (5 wk old). Rats were fed either a control diet
      or diets containing 1% (wt:wt) of GOS-Lu or GOS-La for 14 d. Quantitative
      analysis of carbohydrates from dietary and ileal samples demonstrated that the
      trisaccharide fraction of GOS-Lu was significantly more resistant to gut
      digestion than that from GOS-La, as indicated by their ileal digestibility rates
      of 12.5 +/- 2.6% and 52.9 +/- 2.7%, respectively, whereas the disaccharide
      fraction of GOS-Lu was fully resistant to the extreme environment of the upper
      digestive tract. The low ileal digestibility of GOS-Lu was due to the great
      resistance of galactosyl-fructoses to mammalian digestive enzymes, highlighting
      the key role played by the monomer type and linkage involved in the
      oligosaccharide chain. The partial digestion of GOS-La trisaccharides showed that
      glycosidic linkages (1->6) and (1->2) between galactose and glucose monomers were
      significantly more resistant to in vivo gastrointestinal digestion than the
      linkage (1->4) between galactose units. The absence of GOS-La and GOS-Lu
      digestion-resistant oligosaccharides in fecal samples indicated that they were
      readily fermented within the large intestine, enabling both types of GOS to have
      a potential prebiotic function. Indeed, compared with controls, the GOS-Lu group
      had significantly more bifidobacteria in fecal samples after 14 d of treatment.
      The number of Eubacterium rectale also was greater in the GOS-Lu and GOS-La
      groups than in controls. These novel data support a direct relationship between
      patterns of resistance to digestion and prebiotic properties of GOS.

PMID- 22649258
TI  - Preventing gastric sieving by blending a solid/water meal enhances satiation in
      healthy humans.
AB  - Separation of solids and liquids within the stomach allows faster gastric
      emptying of liquids compared with solids, a phenomenon known as sieving. We
      tested the hypothesis that blending a solid and water meal would abolish sieving,
      preventing the early rapid decrease in gastric volume and thereby enhancing
      satiety. We carried out 2 separate studies. Study 1 was a 2-way, crossover,
      satiety study of 22 healthy volunteers who consumed roasted chicken and
      vegetables with a glass of water (1008 kJ) or the same blended to a soup. They
      completed satiety visual analogue scales at intervals for 3 h. Study 2 was a 2
      way, crossover, mechanistic study of 18 volunteers who consumed the same meals
      and underwent an MRI to assess gastric emptying, gallbladder contraction, and
      small bowel water content (SBWC) at intervals for 3 h. In Study 1, the soup meal
      was associated with reduced hunger (P = 0.02). In Study 2, the volume of the
      gastric contents after the soup meal decreased more slowly than after the
      solid/liquid meal (P = 0.0003). The soup meal caused greater gallbladder
      contraction (P < 0.04). SBWC showed a biphasic response with an initial "gastric"
      phase during which SBWC was greater when the solid/liquid meal was consumed (P <
      0.001) and a later "small bowel" phase when SBWC was greater when the soup meal
      was consumed (P < 0.01). Blending the solid/liquid meal to a soup delayed gastric
      emptying and increased the hormonal response to feeding, which may contribute to
      enhanced postprandial satiety.

PMID- 22649260
TI  - Filling America's fiber intake gap: summary of a roundtable to probe realistic
      solutions with a focus on grain-based foods.
AB  - Current fiber intakes are alarmingly low, with long-term implications for public
      health related to risk of coronary heart disease, stroke, hypertension, certain
      gastrointestinal disorders, obesity, and the continuum of metabolic dysfunctions
      including prediabetes and type 2 diabetes. Eating patterns high in certain fibers
      are known to lower LDL cholesterol and blood pressure, lower blood glucose, and
      decrease insulin resistance in people with prediabetes and type 2 diabetes; help
      with both weight loss and maintenance; and improve bowel regularity and
      gastrointestinal health. With >90% of adults and children who fall short of
      meeting their daily fiber recommendations, the 2010 Dietary Guidelines for
      Americans once again classified fiber as a nutrient of concern. Despite efforts
      over the past decade to promote adequate fiber through fruit, vegetable, and
      whole-grain intakes, fiber consumption has remained flat at approximately half
      the daily recommended amount. The public health implications of inadequate fiber
      intake prompted the roundtable session "Filling America's Fiber Gap: Probing
      Realistic Solutions," which assembled nutrition researchers, educators, and
      communicators to identify challenges, opportunities, and realistic solutions to
      help fill the current fiber gap. The roundtable discussions highlighted the need
      for both consumer and professional education to improve acceptance for and
      inclusion of grain-based foods with added fiber as one strategy for increasing
      fiber intakes within daily energy goals.

PMID- 22649259
TI  - Proteomic approaches to predict bioavailability of fatty acids and their
      influence on cancer and chronic disease prevention.
AB  - A low intake of fish and PUFA and high dietary trans- and SFA are considered to
      be among the main preventable causes of death. Unfortunately, epidemiological and
      preclinical studies have yet to identify biomarkers that accurately predict the
      influence of fatty acid intake on risk of chronic diseases, including cancer.
      Changes in protein profile and post-translational modifications in tissue and
      biofluids may offer important clues about the impact of fatty acids on the
      etiology of chronic diseases. However, conventional protein methodologies are not
      adequate for assessing the impact of fatty acids on protein expression patterns
      and modifications and the discovery of protein biomarkers that predict changes in
      disease risk and progression in response to fatty acid intake. Although
      fluctuations in protein structure and abundance and inter-individual variability
      often mask subtle effects caused by dietary intervention, modern proteomic
      platforms offer tremendous opportunities to increase the sensitivity of protein
      analysis in tissues and biofluids (plasma, urine) and elucidate the effects of
      fatty acids on regulation of protein networks. Unfortunately, the number of
      studies that adopted proteomic tools to investigate the impact of fatty acids on
      disease risk and progression is quite small. The future success of proteomics in
      the discovery of biomarkers of fatty acid nutrition requires improved
      accessibility and standardization of proteomic methodologies, validation of
      quantitative and qualitative protein changes (e.g., expression levels, post
      translational modifications) induced by fatty acids, and application of
      bioinformatic tools that can inform about the cause-effect relationships between
      fatty acid intake and health response.

PMID- 22649261
TI  - Maternal micronutrient supplementation suppresses T cell chemokine receptor
      expression and function in F1 mice.
AB  - Prenatal environmental exposures play a critical role in determining late-life
      chronic disease susceptibility. However, the mechanisms linking the in utero
      environment and disease development in the offspring are poorly understood.
      Recent investigations have confirmed a central pathogenic role of T cell
      chemokine receptors, particularly C-C chemokine receptor (CCR) 2 and CCR5, in
      chronic inflammatory conditions. This study was designed to determine the effect
      of a synthetic prenatal micronutrient supplementation (MS) diet rich in
      methionine pathway metabolites on the T cell chemokine system in F1 C57Bl/6 mice.
      Female mice were fed either an MS or control diet 3 wk prior to mating, during
      pregnancy, and lactation. At 4 wk of age, F1 mice were killed for experiments or
      were fed the standard NIH-31 diet and allowed to age. Food consumption, maternal
      weight gain, and litter size were similar in dams fed the control and MS diets.
      However, the F1 offspring of dams fed the MS diet were smaller in size (P <
      0.001). T cells from the MS F1 offspring had global hypermethylation compared
      with control F1 offspring (P < 0.005), corresponding to lower T cell chemokine
      receptor expression [CCR2 (P < 0.001), CCR5 (P < 0.001), and C-x-C chemokine
      receptor 3 (P < 0.01)] and cytokine expression [TNFalpha (P < 0.05), IL-2 (P <
      0.001), and IL-4 (P < 0.01)]. Reduced T cell chemokine receptor gene expression
      in MS F1 mice was associated with decreased chemotaxis in vitro to C-C chemokine
      ligand (CCL) 2 and C-X-C chemokine ligand 10 (P < 0.01) and in vivo to CCL2 (P <
      0.01). Taken together, the results suggest that epigenetic alteration through
      prenatal diet manipulation reduces the response to proinflammatory signals in
      mice.

PMID- 22649263
TI  - 454 pyrosequencing reveals a shift in fecal microbiota of healthy adult men
      consuming polydextrose or soluble corn fiber.
AB  - The relative contribution of novel fibers such as polydextrose and soluble corn
      fiber (SCF) to the human gut microbiome and its association with host physiology
      has not been well studied. This study was conducted to test the impact of
      polydextrose and SCF on the composition of the human gut microbiota using 454
      pyrosequencing and to identify associations among fecal microbiota and
      fermentative end-products. Healthy adult men (n = 20) with a mean dietary fiber
      (DF) intake of 14 g/d were enrolled in a randomized, double-blind, placebo
      controlled crossover study. Participants consumed 3 treatment snack bars/d during
      each 21-d period that contained no supplemental fiber (NFC), polydextrose (PDX;
      21 g/d), or SCF (21 g/d) for 21 d. There were no washout periods. Fecal samples
      were collected on d 16-21 of each period; DNA was extracted, followed by
      amplification of the V4-V6 region of the 16S rRNA gene using barcoded primers.
      PDX and SCF significantly affected the relative abundance of bacteria at the
      class, genus, and species level. The consumption of PDX and SCF led to greater
      fecal Clostridiaceae and Veillonellaceae and lower Eubacteriaceae compared with a
      NFC. The abundance of Faecalibacterium, Phascolarctobacterium, and Dialister was
      greater (P < 0.05) in response to PDX and SCF intake, whereas Lactobacillus was
      greater (P < 0.05) only after SCF intake. Faecalibacterium prausnitzii, well
      known for its antiinflammatory properties, was greater (P < 0.05) after fiber
      consumption. Principal component analysis clearly indicated a distinct clustering
      of individuals consuming supplemental fibers. Our data demonstrate a beneficial
      shift in the gut microbiome of adults consuming PDX and SCF, with potential
      application as prebiotics.

PMID- 22649262
TI  - Opportunities and challenges for nutritional proteomics in cancer prevention.
AB  - Knowledge gaps persist about the efficacy of cancer prevention strategies based
      on dietary food components. Adaptations to nutrient supply are executed through
      tuning of multiple protein networks that include transcription factors, histones,
      modifying enzymes, translation factors, membrane and nuclear receptors, and
      secreted proteins. However, the simultaneous quantitative and qualitative
      measurement of all proteins that regulate cancer processes is not practical using
      traditional protein methodologies. Proteomics offers an attractive opportunity to
      fill this knowledge gap and unravel the effects of dietary components on protein
      networks that impinge on cancer. The articles presented in this supplement are
      from talks proffered in the "Nutrition Proteomics and Cancer Prevention" session
      at the American Institute for Cancer Research Annual Research Conference on Food,
      Nutrition, Physical Activity and Cancer held in Washington, DC on October 21 and
      22, 2010. Recent advances in MS technologies suggest that studies in nutrition
      and cancer prevention may benefit from the adoption of proteomic tools to
      elucidate the impact on biological processes that govern the transition from
      normal to malignant phenotype; to identify protein changes that determine both
      positive and negative responses to food components; to assess how protein
      networks mediate dose-, time-, and tissue-dependent responses to food components;
      and, finally, for predicting responders and nonresponders. However, both the
      limited accessibility to proteomic technologies and research funding appear to be
      hampering the routine adoption of proteomic tools in nutrition and cancer
      prevention research.

PMID- 22649264
TI  - Low-glycemic load decreases postprandial insulin and glucose and increases
      postprandial ghrelin in white but not black women.
AB  - Alterations in appetite hormones favoring increased postprandial satiety have
      been implicated in both the glycemic control and potential weight-loss benefits
      of a low-glycemic diet. Racial differences exist in dietary glycemic load and
      appetite hormone concentrations. This study examined the impact of glycemic load
      on appetite hormones in 20 black women [10 normal weight, BMI = 22.8 +/- 1.42
      (mean +/- SD); 10 obese, BMI = 35.1 +/- 2.77] and 20 white women (10 normal
      weight, BMI = 22.9 +/- 1.45; 10 obese, BMI = 34.3 +/- 2.77). Each woman completed
      two 4.5-d weight-maintenance, mixed-macronutrient, high-glycemic vs. low-glycemic
      load diets that concluded with a test meal of identical composition. Blood
      samples collected before and serially for 3 h after each test meal were assayed
      for plasma ghrelin and serum insulin and glucose concentrations. Compared with
      the high-glycemic load meal, the low-glycemic load meal was associated with lower
      insulin(AUC) (P = 0.02), glucose(AUC) (P = 0.01), and urge to eat ratings (P =
      0.05) but with higher ghrelin(AUC) (P = 0.008). These results suggest the
      satiating effect of a low-glycemic load meal is not directly linked to enhanced
      postprandial suppression of ghrelin. Notably, these effects were significant
      among white but not black women, suggesting that black women may be less
      sensitive than white women to the glucoregulatory effects of a low-glycemic load.
      These findings add to a growing literature demonstrating racial differences in
      postprandial appetite hormone responses. If reproducible, these findings have
      implications for individualized diet prescription for the purposes of glucose or
      weight control in women.

PMID- 22649266
TI  - Greater whole-grain intake is associated with lower risk of type 2 diabetes,
      cardiovascular disease, and weight gain.
AB  - Whole-grain and high fiber intakes are routinely recommended for prevention of
      vascular diseases; however, there are no comprehensive and quantitative
      assessments of available data in humans. The aim of this study was to
      systematically examine longitudinal studies investigating whole-grain and fiber
      intake in relation to risk of type 2 diabetes (T2D), cardiovascular disease
      (CVD), weight gain, and metabolic risk factors. We identified 45 prospective
      cohort studies and 21 randomized-controlled trials (RCT) between 1966 and
      February 2012 by searching the Cumulative Index to Nursing and Allied Health
      Literature, Cochrane, Elsevier Medical Database, and PubMed. Study
      characteristics, whole-grain and dietary fiber intakes, and risk estimates were
      extracted using a standardized protocol. Using random effects models, we found
      that compared with never/rare consumers of whole grains, those consuming 48-80 g
      whole grain/d (3-5 serving/d) had an ~26% lower risk of T2D [RR = 0.74 (95% CI:
      0.69, 0.80)], ~21% lower risk of CVD [RR = 0.79 (95% CI: 0.74, 0.85)], and
      consistently less weight gain during 8-13 y (1.27 vs 1.64 kg; P = 0.001). Among
      RCT, weighted mean differences in post-intervention circulating concentrations of
      fasting glucose and total and LDL-cholesterol comparing whole-grain intervention
      groups with controls indicated significantly lower concentrations after whole
      grain interventions [differences in fasting glucose: -0.93 mmol/L (95% CI: -1.65,
      -0.21), total cholesterol: -0.83 mmol/L (-1.23, -0.42); and LDL-cholesterol: 
      0.82 mmol/L (-1.31, -0.33)]. [corrected] Findings from this meta-analysis provide
      evidence to support beneficial effects of whole-grain intake on vascular disease
      prevention. Potential mechanisms responsible for whole grains' effects on
      metabolic intermediates require further investigation in large intervention
      trials.

PMID- 22649265
TI  - Use of lipid-based nutrient supplements by HIV-infected Malawian women during
      lactation has no effect on infant growth from 0 to 24 weeks.
AB  - The Breastfeeding, Antiretrovirals, and Nutrition Study evaluated the effect of
      daily consumption of lipid-based nutrient supplements (LNS) by 2121 lactating,
      HIV-infected mothers on the growth of their exclusively breast-fed, HIV
      uninfected infants from 0 to 24 wk. The study had a 2 * 3 factorial design.
      Malawian mothers with CD4(+) >=250 cells/mm(3), hemoglobin >=70 g/L, and BMI >=17
      kg/m(2) were randomized within 36 h of delivery to receive either no LNS or 140
      g/d of LNS to meet lactation energy and protein needs, and mother-infant pairs
      were assigned to maternal antiretroviral drugs (ARV), infant ARV, or no ARV. Sex
      stratified, longitudinal, random effects models were used to estimate the effect
      of the 6 study arms on infant weight, length, and BMI. Logistic regression models
      were used to calculate the odds of growth faltering [decline in weight-for-age Z
      score (WAZ) or length-for-age Z-score (LAZ) >0.67] using the control arm as the
      reference. Although some differences between study arms emerged with increasing
      infant age in boys, there were no consistent effects of the maternal supplement
      across the 3 growth outcomes in longitudinal models. At the ages where
      differences were observed, the effects on weight and BMI were quite small (<=200
      g and <=0.4 kg/m(2)) and unlikely to be of clinical importance. Overall, 21 and
      34% of infants faltered in WAZ and LAZ, respectively. Maternal supplementation
      did not reduce the odds of infant weight or length faltering from 0 to 24 wk in
      any arm. These results indicate that blanket supplementation of HIV-infected
      lactating women may have little impact on infant growth.

PMID- 22649267
TI  - Proteomic analysis of covalent modifications of tubulins by isothiocyanates.
AB  - Although isothiocyanates (ITC), which are found in cruciferous vegetables, have
      been shown to inhibit carcinogenesis in animal models and induce apoptosis and
      cell cycle arrest in tumor cells, the biochemical mechanisms of cell growth
      inhibition by these compounds are not fully understood. Studies have reported
      that ITC binding to intracellular proteins may be an important event for
      initiating apoptosis. Specific protein target(s) and molecular mechanisms for ITC
      have been investigated in human lung cancer A549 cells using proteomic tools.
      Cells were treated with various amounts (1-100 MUmol/L) of radiolabeled phenethyl
      ITC (PEITC) and sulforaphane (SFN) and the extracted proteins resolved using 2
      dimensional gel electrophoresis. The results of mass spectrometric analyses
      suggested that tubulin may be an in vivo binding target for ITC. The binding of
      ITC to tubulin was associated with growth arrest. The proliferation of A549 cells
      was significantly reduced by ITC, with benzyl-ITC (BITC) having a greater
      relative activity than PEITC or SFN. Mitotic arrest and apoptosis as well as
      disruption of microtubule polymerization were induced in the order: BITC > PEITC
      > SFN. An analysis of tubulins isolated from BITC-treated A549 cells showed that
      Cys(347), a conserved cysteine in all alpha-tubulin isoforms, was covalently
      modified by BITC. Taken together, these results suggest that tubulin is a binding
      target of ITC and that this interaction can lead to growth inhibition and
      apoptosis.

PMID- 22649270
TI  - Contribution of CoA ligases to benzenoid biosynthesis in petunia flowers.
AB  - Biosynthesis of benzoic acid from Phe requires shortening of the side chain by
      two carbons, which can occur via the beta-oxidative or nonoxidative pathways. The
      first step in the beta-oxidative pathway is cinnamoyl-CoA formation, likely
      catalyzed by a member of the 4-coumarate:CoA ligase (4CL) family that converts a
      range of trans-cinnamic acid derivatives into the corresponding CoA thioesters.
      Using a functional genomics approach, we identified two potential CoA-ligases
      from petunia (Petunia hybrida) petal-specific cDNA libraries. The cognate
      proteins share only 25% amino acid identity and are highly expressed in petunia
      corollas. Biochemical characterization of the recombinant proteins revealed that
      one of these proteins (Ph-4CL1) has broad substrate specificity and represents a
      bona fide 4CL, whereas the other is a cinnamate:CoA ligase (Ph-CNL). RNA
      interference suppression of Ph-4CL1 did not affect the petunia benzenoid scent
      profile, whereas downregulation of Ph-CNL resulted in a decrease in emission of
      benzylbenzoate, phenylethylbenzoate, and methylbenzoate. Green fluorescent
      protein localization studies revealed that the Ph-4CL1 protein is localized in
      the cytosol, whereas Ph-CNL is in peroxisomes. Our results indicate that
      subcellular compartmentalization of enzymes affects their involvement in the
      benzenoid network and provide evidence that cinnamoyl-CoA formation by Ph-CNL in
      the peroxisomes is the committed step in the beta-oxidative pathway.

PMID- 22649271
TI  - Evolution of double positive autoregulatory feedback loops in CYCLOIDEA2 clade
      genes is associated with the origin of floral zygomorphy.
AB  - Members of the CYCLOIDEA2 (CYC2) clade of the TEOSINTE BRANCHED1, CYCLOIDEA, and
      PCF transcription factor genes are widely involved in controlling floral
      zygomorphy, a key innovation in angiosperm evolution, depending on their
      persistently asymmetric expression in the corresponding floral domains. However,
      it is unclear how this asymmetric expression is maintained throughout floral
      development. Selecting Primulina heterotricha as a model, we examined the
      expression and function of two CYC2 genes, CYC1C and CYC1D. We analyzed the role
      of their promoters in protein-DNA interactions and transcription activation using
      electrophoresis mobility shift assays, chromatin immunoprecipitation, and
      transient gene expression assays. We find that CYC1C and CYC1D positively
      autoregulate themselves and cross-regulate each other. Our results reveal a
      double positive autoregulatory feedback loop, evolved for a pair of CYC2 genes to
      maintain their expression in developing flowers. Further comparative genome
      analyses, together with the available expression and function data of CYC2 genes
      in the core eudicots, suggest that this mechanism might have led to the
      independent origins of floral zygomorphy, which are associated with plant-insect
      coevolution and the adaptive radiation of angiosperms.

PMID- 22649272
TI  - Endoplasmic reticulum-quality control chaperones facilitate the biogenesis of Cf
      receptor-like proteins involved in pathogen resistance of tomato.
AB  - Cf proteins are receptor-like proteins (RLPs) that mediate resistance of tomato
      (Solanum lycopersicum) to the foliar pathogen Cladosporium fulvum. These
      transmembrane immune receptors, which carry extracellular leucine-rich repeats
      that are subjected to posttranslational glycosylation, perceive effectors of the
      pathogen and trigger a defense response that results in plant resistance. To
      identify proteins required for the functionality of these RLPs, we performed
      immunopurification of a functional Cf-4-enhanced green fluorescent protein fusion
      protein transiently expressed in Nicotiana benthamiana, followed by mass
      spectrometry. The endoplasmic reticulum (ER) heat shock protein70 binding
      proteins (BiPs) and lectin-type calreticulins (CRTs), which are chaperones
      involved in ER-quality control, were copurifying with Cf-4-enhanced green
      fluorescent protein. The tomato and N. benthamiana genomes encode four BiP
      homologs and silencing experiments revealed that these BiPs are important for
      overall plant viability. For the three tomato CRTs, virus-induced gene silencing
      targeting the plant-specific CRT3a gene resulted in a significantly compromised
      Cf-4-mediated defense response and loss of full resistance to C. fulvum. We show
      that upon knockdown of CRT3a the Cf-4 protein accumulated, but the pool of Cf-4
      protein carrying complex-type N-linked glycans was largely reduced. Together, our
      study on proteins required for Cf function reveals an important role for the CRT
      ER chaperone CRT3a in the biogenesis and functionality of this type of RLP
      involved in plant defense.

PMID- 22649273
TI  - A constitutive expressed phosphate transporter, OsPht1;1, modulates phosphate
      uptake and translocation in phosphate-replete rice.
AB  - A number of phosphate (Pi) starvation- or mycorrhiza-regulated Pi transporters
      belonging to the Pht1 family have been functionally characterized in several
      plant species, whereas functions of the Pi transporters that are not regulated by
      changes in Pi supply are lacking. In this study, we show that rice (Oryza sativa)
      Pht1;1 (OsPT1), one of the 13 Pht1 Pi transporters in rice, was expressed
      abundantly and constitutively in various cell types of both roots and shoots.
      OsPT1 was able to complement the proton-coupled Pi transporter activities in a
      yeast mutant defective in Pi uptake. Transgenic plants of OsPT1 overexpression
      lines and RNA interference knockdown lines contained significantly higher and
      lower phosphorus concentrations, respectively, compared with the wild-type
      control in Pi-sufficient shoots. These responses of the transgenic plants to Pi
      supply were further confirmed by the changes in depolarization of root cell
      membrane potential, root hair occurrence, (33)P uptake rate and transportation,
      as well as phosphorus accumulation in young leaves at Pi-sufficient levels.
      Furthermore, OsPT1 expression was strongly enhanced by the mutation of Phosphate
      Overaccumulator2 (OsPHO2) but not by Phosphate Starvation Response2, indicating
      that OsPT1 is involved in the OsPHO2-regulated Pi pathway. These results indicate
      that OsPT1 is a key member of the Pht1 family involved in Pi uptake and
      translocation in rice under Pi-replete conditions.

PMID- 22649275
TI  - Trends in Educational Attainment by Race/Ethnicity, Nativity, and Sex in the
      United States, 1989-2005.
AB  - Despite the importance of education for shaping individuals' life chances, little
      research has examined trends and differences in educational attainment for
      detailed demographic subpopulations in the United States. We use labor market
      segmentation and cohort replacement theories, linear regression methods, and data
      from the National Health Interview Survey to understand educational attainment by
      race/ethnicity, nativity, birth cohort, and sex between 1989 and 2005 in the
      United States. There have been significant changes in educational attainment over
      time. In support of the cohort replacement theory, we find that across cohorts,
      females have enjoyed greater gains in education than men, and for some
      race/ethnic groups, recent cohorts of women average more years of education than
      comparable men. And in support of labor market segmentation theories, foreign
      born Mexican Americans continue to possess relatively low levels of educational
      attainment. Our results can aid policymakers in identifying vulnerable
      populations, and form the base from which to better understand changing
      disparities in education.

PMID- 22649276
TI  - Activation of human neutrophils by the anti-inflammatory mediator Esenbeckia
      leiocarpa leads to atypical apoptosis.
AB  - Despite the fact that Esenbeckia leiocarpa, a Brazilian plant, possesses
      potential anti-inflammatory properties, its effect in neutrophils, key players in
      inflammation, has never been investigated. In this study, a crude hydroalcoholic
      extract (CHE) was used to evaluate the potential toxic or agonistic effect of E.
      leiocarpa in human neutrophils. At a noncytotoxic concentration of 500 MUg/mL,
      CHE increased actin polymerization and cell signaling events, especially p38
      MAPK. Its modulatory activity on neutrophil cell apoptosis was investigated by
      cytology and by flow cytometry and, although CHE increased the apoptotic rate (by
      cytology) and increased annexin-V binding, it did not, unexpectedly, increase
      CD16 shedding. CHE increased the degradation of the cytoskeletal proteins
      gelsolin and paxillin but, surprisingly, not of vimentin. The proapoptotic
      activity of CHE was reversed by a pan-caspase inhibitor but not by a p38
      inhibitor. We conclude that CHE is a novel human neutrophil agonist that induces
      apoptosis by a caspase-dependent and p38-independent mechanism in an atypical
      fashion based on its lack of effect on CD16 shedding and vimentin degradation.
      Since the resolution of inflammation occurs by elimination of apoptotic
      neutrophils, the ability of CHE to induce neutrophil apoptosis correlates well
      with its anti-inflammatory properties, as previously reported.

PMID- 22649274
TI  - Characterization of a glucosyltransferase enzyme involved in the formation of
      kaempferol and quercetin sophorosides in Crocus sativus.
AB  - UGT707B1 is a new glucosyltransferase isolated from saffron (Crocus sativus) that
      localizes to the cytoplasm and the nucleus of stigma and tepal cells. UGT707B1
      transcripts were detected in the stigma tissue of all the Crocus species
      analyzed, but expression analysis of UGT707B1 in tepals revealed its absence in
      certain species. The analysis of the glucosylated flavonoids present in Crocus
      tepals reveals the presence of two major flavonoid compounds in saffron:
      kaempferol-3-O-beta-D-glucopyranosyl-(1-2)-beta-D-glucopyranoside and quercetin-3
      O-beta-D-glucopyranosyl-(1-2)-beta-D-glucopyranoside, both of which were absent
      from the tepals of those Crocus species that did not express UGT707B1. Transgenic
      Arabidopsis (Arabidopsis thaliana) plants constitutively expressing UGT707B1
      under the control of the cauliflower mosaic virus 35S promoter have been
      constructed and their phenotype analyzed. The transgenic lines displayed a number
      of changes that resembled those described previously in lines where flavonoid
      levels had been altered. The plants showed hyponastic leaves, a reduced number of
      trichomes, thicker stems, and flowering delay. Levels of flavonoids measured in
      extracts of the transgenic plants showed changes in the composition of flavonols
      when compared with wild-type plants. The major differences were observed in the
      extracts from stems and flowers, with an increase in 3-sophoroside flavonol
      glucosides. Furthermore, a new compound not detected in ecotype Columbia wild
      type plants was detected in all the tissues and identified as kaempferol-3-O
      sophoroside-7-O-rhamnoside. These data reveal the involvement of UGT707B1 in the
      biosynthesis of flavonol-3-O-sophorosides and how significant changes in
      flavonoid homeostasis can be caused by the overproduction of a flavonoid
      conjugating enzyme.

PMID- 22649278
TI  - New protein vector ApE1 for targeted delivery of anticancer drugs.
AB  - A new chimeric gene ApE1 encoding the receptor-binding domain of the human alpha
      fetoprotein fused to a sequence of 22 glutamic acid residues was constructed. A
      new bacterial producer strain E. coli SHExT7 ApE1 was selected for ApE1
      production in a soluble state. A simplified method was developed to purify ApE1
      from bacterial biomass. It was shown that the new vector protein selectively
      interacts with AFP receptors on the tumor cell surface and can be efficiently
      accumulated in tumor cells. In addition, ApE1 was shown to be stable in storage
      and during its chemical modification. An increased number of carboxyl groups in
      the molecule allows the production of cytotoxic compound conjugates with higher
      drug-loading capacity and enhanced tumor targeting potential.

PMID- 22649277
TI  - The current state of knowledge of hepatic ischemia-reperfusion injury based on
      its study in experimental models.
AB  - The present review focuses on the numerous experimental models used to study the
      complexity of hepatic ischemia/reperfusion (I/R) injury. Although experimental
      models of hepatic I/R injury represent a compromise between the clinical reality
      and experimental simplification, the clinical transfer of experimental results is
      problematic because of anatomical and physiological differences and the
      inevitable simplification of experimental work. In this review, the strengths and
      limitations of the various models of hepatic I/R are discussed. Several
      strategies to protect the liver from I/R injury have been developed in animal
      models and, some of these, might find their way into clinical practice. We also
      attempt to highlight the fact that the mechanisms responsible for hepatic I/R
      injury depend on the experimental model used, and therefore the therapeutic
      strategies also differ according to the model used. Thus, the choice of model
      must therefore be adapted to the clinical question being answered.

PMID- 22649279
TI  - Effect of colic vein ligature in rats with loperamide-induced constipation.
AB  - INTRODUCTION: Medical treatment in chronic constipation is not always successful.
      Surgery is indicated in unresponsive selected severe cases. This study presents
      the distal venous colic ligation in rat as a novel surgical approach. MATERIALS
      AND METHODS: 16 rats (study group) were evaluated in 3 phases of 6 days each: A
      (normal conditions), B (loperamide-induced constipation), and C (colic vein
      legation) and compared with rats treated in phase C with PEG 4,000 (control
      group). Blood biochemical and physiological parameters, daily fecal water content
      (FWC), and histological analysis were performed in all study phases. RESULTS: No
      biochemical and physiological parameters changes were observed. FWC decreased in
      phase B and increased in phase C in both groups with a grow up to 2.3-fold in
      study group compared to control (P < 0.0001). Moreover, in study group, a high
      number of colonic goblet cells were detected (phase C versus phase B: P < 0.001)
      while no differences were registered in control. CONCLUSION: By ligature of the
      colic vein in constipated rats, an increase in FWC and goblet cells higher than
      in PEG treated rats was detected. The described surgical procedure appeared
      effective, simple, and safe; further studies in animal models, however, are
      necessary to assess its clinical applicability.

PMID- 22649280
TI  - Suppression of human breast tumors in NOD/SCID mice by CD44 shRNA gene therapy
      combined with doxorubicin treatment.
AB  - BACKGROUND: Breast cancer stem cells with a CD44(+)CD24(-) phenotype are the
      origin of breast tumors. Strong CD44 expression in this population indicates its
      important role in maintaining the stem cell phenotype. Previous studies show that
      CD44 down-regulation causes CD44(+)CD24(-) breast cancer stem cells to
      differentiate into non-stem cells that are sensitive to antitumor drugs and lose
      many characteristics of the original cells. In this study, we determined tumor
      suppression in non-obese severe combined immunodeficiency mice using CD44 shRNA
      therapy combined with doxorubicin treatment. METHODS: Tumor-bearing non-obese
      severe combined immunodeficiency mice were established by injection of
      CD44(+)CD24(-) cells. To track CD44(+)CD24(-) cells, green fluorescence protein
      was stably transduced using a lentiviral vector prior to injection into mice. The
      amount of CD44 shRNA lentiviral vector used for transduction was based on CD44
      down-regulation by in vitro CD44 shRNA transduction. Mice were treated with
      direct injection of CD44 shRNA lentiviral vector into tumors followed by
      doxorubicin administration after 48 hours. The effect was evaluated by changes in
      the size and weight of tumors compared with that of the control. RESULTS: The
      combination of CD44 down-regulation and doxorubicin strongly suppressed tumor
      growth with significant differences in tumor sizes and weights compared with that
      of CD44 down-regulation or doxorubicin treatment alone. In the combination of
      CD44 down-regulation and doxorubicin group, the tumor weight was significantly
      decreased by 4.38-fold compared with that of the control group. CONCLUSION: These
      results support a new strategy for breast cancer treatment by combining gene
      therapy with chemotherapy.

PMID- 22649282
TI  - Florabank1: a grid-based database on vascular plant distribution in the northern
      part of Belgium (Flanders and the Brussels Capital region).
AB  - Florabank1 is a database that contains distributional data on the wild flora
      (indigenous species, archeophytes and naturalised aliens) of Flanders and the
      Brussels Capital Region. It holds about 3 million records of vascular plants,
      dating from 1800 till present. Furthermore, it includes ecological data on
      vascular plant species, redlist category information, Ellenberg values, legal
      status, global distribution, seed bank etc. The database is an initiative of
      "Flo.Wer" (www.plantenwerkgroep.be), the Research Institute for Nature and Forest
      (INBO: www.inbo.be) and the National Botanic Garden of Belgium (www.br.fgov.be).
      Florabank aims at centralizing botanical distribution data gathered by both
      professional and amateur botanists and to make these data available to the
      benefit of nature conservation, policy and scientific research.The occurrence
      data contained in Florabank1 are extracted from checklists, literature and
      herbarium specimen information. Of survey lists, the locality name
      (verbatimLocality), species name, observation date and IFBL square code, the grid
      system used for plant mapping in Belgium (Van Rompaey 1943), is recorded. For
      records dating from the period 1972-2004 all pertinent botanical journals dealing
      with Belgian flora were systematically screened. Analysis of herbarium specimens
      in the collection of the National Botanic Garden of Belgium, the University of
      Ghent and the University of Liege provided interesting distribution knowledge
      concerning rare species, this information is also included in Florabank1. The
      data recorded before 1972 is available through the Belgian GBIF node
      (http://data.gbif.org/datasets/resource/10969/), not through FLORABANK1, to avoid
      duplication of information. A dedicated portal providing access to all published
      Belgian IFBL records at this moment is available at:
      http://projects.biodiversity.be/ifblAll data in Florabank1 is georeferenced.
      Every record holds the decimal centroid coordinates of the IFBL square containing
      the observation. The uncertainty radius is the smallest circle possible covering
      the whole IFBL square, which can measure 1 Km2 or 4 Km2. Florabank is a work in
      progress and new occurrences are added as they become available; the dataset will
      be updated through GBIF on a regularly base.

PMID- 22649281
TI  - Efficacy of esomeprazole in treating acid-related diseases in Japanese
      populations.
AB  - Esomeprazole (Nexium((r)); AstraZeneca), the S-isomer of omeprazole, is the first
      proton pump inhibitor (PPI) to be developed as an optical isomer. Compared with
      omeprazole, esomeprazole has an improved pharmacokinetic profile with regards to
      CYP2C19 (S-mephenytoin 4'-hydroxylase) genotype, showing increased systemic
      exposure and less interindividual variability. Further, esomeprazole is a more
      potent acid inhibitor than other currently available PPIs and is therefore used
      as a first-line drug for acid-related diseases. While esomeprazole has been
      available in a number of countries worldwide, the compound only received
      authorized permission to be marketed in Japan in September 2011. The standard
      esomeprazole dose in Japan for the treatment of peptic ulcers and
      gastroesophageal reflux disease (GERD) is 20 mg. Other advised dosages are 10 mg
      for nonerosive reflux disease and 20 mg twice-daily dosing for eradication of
      Helicobacter pylori. In Japanese, the effective rate of esomeprazole 20 mg during
      24 weeks for GERD patients is 92.0% (88.0%-96.0%), while the prevention of peptic
      ulcer development using 20 mg for 24 weeks in patients treated with nonsteroidal
      anti-inflammatory drugs is 96.0% (92.8%-99.1%). Although clinical data are
      limited, the usefulness of esomeprazole is expected in Japanese subjects given
      the reduced prevalence of CYP2C19 rapid metabolizers in Japan compared with
      Western countries.

PMID- 22649283
TI  - The role of translation initiation regulation in haematopoiesis.
AB  - Organisation of RNAs into functional subgroups that are translated in response to
      extrinsic and intrinsic factors underlines a relatively unexplored gene
      expression modulation that drives cell fate in the same manner as regulation of
      the transcriptome by transcription factors. Recent studies on the molecular
      mechanisms of inflammatory responses and haematological disorders indicate
      clearly that the regulation of mRNA translation at the level of translation
      initiation, mRNA stability, and protein isoform synthesis is implicated in the
      tight regulation of gene expression. This paper outlines how these
      posttranscriptional control mechanisms, including control at the level of
      translation initiation factors and the role of RNA binding proteins, affect
      hematopoiesis. The clinical relevance of these mechanisms in haematological
      disorders indicates clearly the potential therapeutic implications and the need
      of molecular tools that allow measurement at the level of translational control.
      Although the importance of miRNAs in translation control is well recognised and
      studied extensively, this paper will exclude detailed account of this level of
      control.

PMID- 22649284
TI  - Simple technique for augmentation of the facial soft tissue.
AB  - Due to the request of numerous patients to improve the aspect of the perioral
      area in combination with other types of cosmetic and reconstructive surgery, we
      started to use autologous fillers. In fact, there are numerous potential fillers
      that can be utilized during various operations executed in many bodily areas,
      such as the breast, abdomen, and face. The muscular fascia as well as the dense
      connective tissue which the surgeon encounters in various bodily areas during
      some stages of the operation, in fact, can be removed and replaced both by
      themselves or superimposed in order to increase their thickness. The insertion of
      the grafts is carried out by using a needle, but other methods can also be used
      with the same success. The consistency of the area treated, after a few days of
      edema, is very similar to the host area, and the volume obtained remains uniform
      in time (our followup is after 24 months). The time utilized for the removal and
      the insertion in the chosen area was only a few minutes. The result was extremely
      satisfactory in all the 30 patients treated, and there was no complication or
      side effects.

PMID- 22649285
TI  - Deployment of municipal solid wastes as a substitute growing medium component in
      marigold and basil seedlings production.
AB  - The possible use of municipal solid waste compost (MSWC) in the production of
      marigold and basil seedlings examined. Six medium prepared from commercial peat
      (CP) and MSWC (0, 15, 30, 45, 60, and 100% v/v). There was not any plant growth
      when MSWC used alone (100%). The addition of MSWC in low content (15% and 30%)
      improved seed emergence for marigold and basil respectively, while greater
      content revealed opposed impacts. Mean emergence time delayed as MSWC content
      increased into substrates. Addition of MSWC (especially in content greater than
      30%) into CP reduced (from 34 to 64%) plant height, leaf number and stem diameter
      as a consequence reduced plant fresh weight (plant biomass) for both species. The
      number of lateral stems decreased (up to 81%) in basil when MSWC added into
      substrate mixtures. Chlorophyll b content decreased (up to 58%) in substrates
      with MSWC content greater than 15% or 30% while similar reduction observed in
      content of Chlorophyll a and total carotenoids for basil with MSWC > 60%.
      However, Chlorophyll a and total carotenoids content increased as MSWC content
      increased for marigold. K and Na leaf content increased but P equivalent
      decreased as MSWC content increased. Nursery-produced basil and marigold
      seedlings grown in 15% MSWC; displayed quality indices similar to those recorded
      for conventional mixtures of peat and may act as component substitute.

PMID- 22649287
TI  - Longitudinal impact of the project PATHS on adolescent risk behavior: what
      happened after five years?
AB  - The present study investigated the longitudinal impact of the Project PATHS, a
      large-scale curriculum-based positive youth development program in Hong Kong, on
      the development of adolescents' risk behavior over a period of five years. Using
      a longitudinal randomized controlled design, eight waves of data were collected
      from 19 experimental schools in which students participated in the Project PATHS
      (N = 2,850 at Wave 8) and 24 control schools without joining the Project PATHS (N
      = 3,640 at Wave 8). At each wave, students responded to measures assessing their
      current risk behaviors, including delinquency, use of different types of drug,
      and their intentions of participating in risk behaviors in the future. Results
      demonstrated that adolescents receiving the program exhibited significantly
      slower increases in delinquent behaviors and substance use as compared to the
      control participants. During two years after the completion of the program,
      differences in youth risk behaviors in the two groups still existed. These
      results suggest that the Project PATHS has long-term effect in preventing
      adolescent problem behavior through promoting positive youth development.

PMID- 22649286
TI  - Thyroid hormone-induced cytosol-to-nuclear translocation of rat liver Nrf2 is
      dependent on Kupffer cell functioning.
AB  - L-3,3',5-triiodothyronine (T(3)) administration upregulates nuclear factor-E2
      related factor 2 (Nrf2) in rat liver, which is redox-sensitive transcription
      factor mediating cytoprotection. In this work, we studied the role of Kupffer
      cell respiratory burst activity, a process related to reactive oxygen species
      generation and liver homeostasis, in Nrf2 activation using the macrophage
      inactivator gadolinium chloride (GdCl(3); 10 mg/kg i.v. 72 h before T(3) [0.1
      mg/kg i.p.]) or NADPH oxidase inhibitor apocynin (1.5 mmol/L added to the
      drinking water for 7 days before T(3)), and determinations were performed 2 h
      after T(3). T(3) increased nuclear/cytosolic Nrf2 content ratio and levels of
      heme oxygenase 1 (HO-1), catalytic subunit of glutamate cysteine ligase, and
      thioredoxin (Western blot) over control values, proteins whose gene transcription
      is induced by Nrf2. These changes were suppressed by GdCl(3) treatment prior to
      T(3), an agent-eliciting Kupffer-cell depletion, inhibition of colloidal carbon
      phagocytosis, and the associated respiratory burst activity, with enhancement in
      nuclear inhibitor of Nrf2 kelch-like ECH-associated protein 1 (Keap1)/Nrf2
      content ratios suggesting Nrf2 degradation. Under these conditions, T(3)-induced
      tumor necrosis factor-alpha (TNF-alpha) response was eliminated by previous
      GdCl(3) administration. Similar to GdCl(3), apocynin given before T(3)
      significantly reduced liver Nrf2 activation and HO-1 expression, a NADPH oxidase
      inhibitor eliciting abolishment of colloidal carbon-induced respiratory burst
      activity without altering carbon phagocytosis. It is concluded that Kupffer cell
      functioning is essential for upregulation of liver Nrf2-signaling pathway by
      T(3). This contention is supported by suppression of the respiratory burst
      activity of Kupffer cells and the associated reactive oxygen species production
      by GdCl(3) or apocynin given prior to T(3), thus hindering Nrf2 activation.

PMID- 22649288
TI  - Colorectal cancer chemoprevention: is this the future of colorectal cancer
      prevention?
AB  - Colorectal cancer (CRC) is presently one of the most common causes of cancer
      related death in our setting and affects a great number of people each year.
      Screening strategies are commonly used but they do not seem enough to avoid CRC
      development or prevent completely its mortality. Because of this fact other
      prevention strategies have gained interest in recent years. Chemoprevention seems
      to be an attractive option in this setting and several drugs have been studied in
      this field. This review is focused on salicylates, nonsteroidal anti-inflammatory
      drugs (NSAIDs) and cycloxygenase-2 inhibitors (COXIBs), whose mechanism of action
      could be directly related to colon cancer chemoprevention.

PMID- 22649289
TI  - Growth inhibition by caffeic acid, one of the phenolic constituents of honey, in
      HCT 15 colon cancer cells.
AB  - Previous work from our laboratory showed that the mechanism of crude-honey
      induced apoptosis in colon cancer cells. Since phenolic constituents of honey
      were attributed to its apoptosis-inducing ability, we studied caffeic acid, one
      of the phenolic constituents of honey, induced effect on colon cancer cells.
      Antiproliferative effect of caffeic acid was estimated using 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. MTT assay
      signified the antiproliferative nature of caffeic acid against the HCT 15 colon
      cancer cells. A time-dependent inhibition of colony formation was evident with
      caffeic acid treatment. Cell-cycle analysis of caffeic acid- (CA-) treated cells
      indicated increasing accumulation of cells at sub-G(1) phase. Photomicrograph
      images of treated cells showed membrane blebbing and cell shrinkage. Yo-pro-1
      staining of caffeic-acid-treated cells confirmed apoptosis in dose- and time
      dependent manner. Increasing ROS generation and reduction in the mitochondrial
      membrane potential were also accompanied in the caffeic acid-induced apoptosis.
      This work will promote caffeic acid as a likely candidate in the chemoprevention
      of colon cancer.

PMID- 22649290
TI  - Wind tunnel measurement of turbulent and advective scalar fluxes: a case study on
      intersection ventilation.
AB  - The objective of this study is to determine processes of pollution ventilation in
      the X-shaped street intersection in an idealized symmetric urban area for the
      changing approach flow direction. A unique experimental setup for simultaneous
      wind tunnel measurement of the flow velocity and the tracer gas concentration in
      a high temporal resolution is assembled. Advective horizontal and vertical scalar
      fluxes are computed from averaged measured velocity and concentration data within
      the street intersection. Vertical advective and turbulent scalar fluxes are
      computed from synchronized velocity and concentration signals measured in the
      plane above the intersection. All the results are obtained for five approach flow
      directions. The influence of the approach flow on the advective and turbulent
      fluxes is determined. The contribution of the advective and turbulent flux to the
      ventilation is discussed. Wind direction with the best dispersive conditions in
      the area is found. The quadrant analysis is applied to the synchronized signals
      of velocity and concentration fluctuation to determine events with the dominant
      contribution to the momentum flux and turbulent scalar flux.

PMID- 22649291
TI  - World aquaculture: environmental impacts and troubleshooting alternatives.
AB  - Aquaculture has been considered as an option to cope with the world food demand.
      However, criticisms have arisen around aquaculture, most of them related to the
      destruction of ecosystems such as mangrove forest to construct aquaculture farms,
      as well as the environmental impacts of the effluents on the receiving
      ecosystems. The inherent benefits of aquaculture such as massive food production
      and economical profits have led the scientific community to seek for diverse
      strategies to minimize the negative impacts, rather than just prohibiting the
      activity. Aquaculture is a possible panacea, but at present is also responsible
      for diverse problems related with the environmental health; however the new
      strategies proposed during the last decade have proven that it is possible to
      achieve a sustainable aquaculture, but such strategies should be supported and
      proclaimed by the different federal environmental agencies from all countries.
      Additionally there is an urgent need to improve legislation and regulation for
      aquaculture. Only under such scenario, aquaculture will be a sustainable
      practice.

PMID- 22649292
TI  - Evaluation of minerals content of drinking water in Malaysia.
AB  - The drinking and mineral water samples obtained from different geographical
      locations had concentrations of the selected minerals lower than the standard
      limits, except for manganese, arsenic, and fluoride. The concentrations of
      manganese and arsenic in two mineral water samples were slightly higher than the
      standard international recommended limits. One mineral water sample had a
      fluoride concentration higher than the standard limits, whereas manganese was not
      detected in nine drinking and mineral water samples. Most of the selected
      minerals found in the tap water samples were below the international standard
      limits, except for iron and manganese. The concentrations of iron and manganese
      in the tap water samples were higher than the standard limits, which were
      obtained from one and three of the studied locations, respectively. The potable
      water obtained from various manufacturers and locations in Peninsular Malaysia is
      safe for consumption, as the minerals concentrations were below the standard
      limits prescribed by the Malaysian Food Regulations of 1985. The data obtained
      may also provide important information related to daily intake of these minerals
      from drinking water.

PMID- 22649293
TI  - Seroprevalence survey of American trypanosomiasis in Central Valley of Toluca.
AB  - American trypanosomiasis is a growing health issue in the Americas. Mexico is an
      endemic country, where some locations such as in the State of Mexico are
      considered highly prevalent. In the valley of Toluca city, the capital of the
      State of Mexico, there exists an apparent high prevalence in dogs. The absence of
      triatomine vectors suggests that dogs may not be infected. Therefore, we
      conducted a directed survey to domiciliated and nondomiciliated dogs to reassess
      dogs' T. cruzi seroprevalence status. HAI and ELISA serologic tests were applied
      to 124 and 167 serums of domiciliated and nondomiciliated dogs in the target
      city. Risk factors were estimated, but the results did not show any evidence to
      assess them. No domiciliated dogs tested positive to both tests, whereas only one
      non-domiciliated dog resulted positive. This animal may have acquired the
      infection in an endemic area and then migrated to Toluca. Research results
      indicate that T. cruzi infection is not actively transmitted among dogs, and it
      is pointed out that dogs are the main sentinel animal population to evaluate a
      possible expansion of the territory affected by Chagas' disease.

PMID- 22649294
TI  - Analysis of quality of nuchal translucency measurements: its role in prenatal
      diagnosis.
AB  - OBJECTIVE: Quantitative analysis of the quality of nuchal translucency (NT)
      measurements. METHODS: First-trimester combined screening for Down syndrome was
      performed to all pregnant women attended in our Department from October 2003 to
      November 2009. NT was measured according to the Fetal Medicine Foundation (FMF)
      criteria by 20 trained obstetricians. The performance of NT measurements was
      retrospectively analyzed with regard to several quality control standards.
      Accuracy according to experience, professional profile, crown rump length (CRL)
      values, and FMF certification was statistically tested. RESULTS: A total of 14978
      NT measurements were assessed. (1) The mean operator-specific median NT-MoM
      values was 0,98. (2) Mean percentage of cases >95th and <5th centiles were 5,0%
      and 4,2%, respectively. (3) Logarithmic mean and SD of the NT MoM values were
      0,00 and 0,13, respectively. (4) The DR for trisomy 21 at screening time was
      90,7% for a FPR of 6,7% for standard screening strategy. (5) According to
      Cumulative SUM (CUSUM) figures, the performance was more acceptable in FMF
      certified operators. CONCLUSION: Overall, quality standards show optimal NT
      measurements in our unit. Operator experience, a dedicated profile to fetal
      medicine, CRL over 60 mm, and FMF certification have a significant positive
      impact on the quality standards.

PMID- 22649295
TI  - Secondary metabolites of Hypericum leptophyllum Hochst., an endemic Turkish
      species.
AB  - In the present study, the presence of the phloroglucinol derivative hyperforin,
      the naphthodianthrones hypericin and pseudohypericin, the phenylpropane
      chlorogenic acid and the flavonoids rutin, hyperoside, kaempferol, isoquercetine,
      quercitrine, and quercetine was investigated in Hypericum leptophyllum Hochst.,
      an endemic Turkish species for the first time. The aerial parts representing a
      total of 30 individuals were collected at full flowering and dissected into
      floral, leaf, and stem tissues. After being dried at room temperature, the plant
      materials were assayed for secondary metabolite concentrations by HPLC. Aerial
      plant parts accumulated chlorogenic acid, hyperoside, isoquercetine, quercitrine,
      and quercetine, but they did not accumulate hyperforin, hypericin,
      pseudohypericin, rutin, and kaempferol. Accumulation levels of the detected
      compounds varied with plant tissues. Such kind of data could be useful for
      elucidation of the chemotaxonomical significance of the corresponding compounds
      and phytochemical evaluation of this endemic species.

PMID- 22649296
TI  - Positive identity as a positive youth development construct: a conceptual review.
AB  - Identity is a core construct in psychology because it refers to how a person
      addresses issues dealing with who that person is. Important theorists studying
      the concept of identity, like Erikson, Marcia, and Higgins, assert that identity
      is organized,is learned, and is dynamic, and a subjective evaluation of an
      individual's identity has emotional consequences for that individual. Adolescents
      who can cultivate a clear and positive identity after their developmental
      struggles during adolescence often advance more smoothly into adulthood. This
      paper reviews literature on the nature and structure of identity and examines its
      importance on adolescent developmental outcomes. It traces significant
      determinants of identity and proposes strategies for cultivation of positive
      identity. Observations on current research gaps in the study of identity and
      future research directions will also be discussed.

PMID- 22649297
TI  - The growth of Monoraphidium sp. and Scenedesmus sp. cells in the presence of
      thorium.
AB  - Toxicity of thorium by Monoraphidium sp. and Scenedesmus sp. was studied.
      Microalgal cultures were inoculated in ASM-1 medium in presence and absence of
      thorium. Its effect was monitored by direct counting on Fuchs-Rosenthal chamber
      and with software. The toxicity of thorium over the species was observed for
      concentrations over 50.0 mg/L. After 30 days, Monoraphidium cells decreased their
      concentration from 4.23 * 10(6) to 4.27 * 10(5) and 8.57 * 10(5) cells/mL, in the
      presence of 50.0 and 100.0 mg/L of thorium, respectively. Scenedesmus sp. cells
      were more resistant to thorium: for an initial cell concentration of 7.65 * 10(4)
      cells/mL it was observed a change to 5.25 * 10(5) and 5.12 * 10(5) cells/mL, in
      the presence of thorium at 50.0 and 100.0 mg/L, respectively. This is an
      indication that low concentrations of the radionuclide favored the growth, and
      that Scenedesmus cells are more resistant to thorium than Monoraphidium cells.
      The software used for comparison with direct count method proved to be useful for
      the improvement of accuracy of the results obtained, a decrease in the
      uncertainty and allowed recording of the data. The presence of thorium suggests
      that low concentrations have a positive effect on the growth, due to the presence
      of the nitrate, indicating its potential for ecotoxicological studies.

PMID- 22649298
TI  - Trends of rural tropospheric ozone at the northwest of the Iberian Peninsula.
AB  - Tropospheric ozone levels around urban and suburban areas at Europe and North
      America had increased during 80's-90's, until the application of NO(x) reduction
      strategies. However, as it was expected, this ozone depletion was not
      proportional to the emissions reduction. On the other hand, rural ozone levels
      show different trends, with peaks reduction and average increments; this
      different evolution could be explained by either emission changes or climate
      variability in a region. In this work, trends of tropospheric ozone episodes at
      rural sites in the northwest of the Iberian Peninsula were analyzed and compared
      to others observed in different regions of the Atlantic European coast. Special
      interest was focused on the air quality sites characterization, in order to
      guarantee their rural character in terms of air quality. Both episodic local
      meteorological and air quality measurements along five years were considered, in
      order to study possible meteorological influences in ozone levels, different to
      other European Atlantic regions.

PMID- 22649299
TI  - The effects of body acupuncture on obesity: anthropometric parameters, lipid
      profile, and inflammatory and immunologic markers.
AB  - A randomized controlled clinical trial in 196 obese subjects was performed to
      examine the effectiveness of body acupuncture on body weight loss, lipid profile
      and immunogenic and inflammatory markers. Subjects received authentic (cases) or
      sham (controls) acupuncture for 6 weeks in combination with a low-calorie diet.
      In the following 6 weeks, they received the low-calorie diet alone. Subjects were
      assessed at the beginning, 6 and 12 weeks later. Heat shock protein (Hsps)-27,
      60, 65, 70 antibody titers and high sensitivity C-reactive protein (hs-CRP)
      levels were also assessed. A significant reduction in measures of adiposity and
      improvement in lipid profile were observed in both groups, but the levels of anti
      Hsp-antibodies decreased in cases only. A reduction in anthropometric and lipid
      profile in cases were sustained in the second period, however, only changes in
      lipid profile were observed in the control group. Anti-Hsp-antibodies and hs-CRP
      levels continued to be reduced in cases but in controls only the reduction in hs
      CRP remained. Changes in anthropometric parameters, lipid profile, and anti-Hsp
      antibodies were more evident in cases. Body acupuncture in combination with diet
      restriction was effective in enhancing weight loss and improving dyslipidemia.

PMID- 22649300
TI  - Preconcentration of trace amounts of Pb(II) ions without any chelating agent by
      using magnetic iron oxide nanoparticles prior to ETAAS determination.
AB  - This work investigates the potential of magnetic Fe(3)O(4) nanoparticles as an
      adsorbent for separation and preconcentration of trace amounts of lead from water
      samples prior to electrothermal atomic absorption spectrometry (ETAAS)
      determination. No chemical modifier is required in graphite furnace. Pb(II) ion
      was adsorbed on magnetic Fe(3)O(4) nanoparticles in the pH range of 5.5-6.5, and
      then magnetic nanoparticles (MNPs) were easily separated from the aqueous
      solution by applying an external magnetic field; so, no filtration or
      centrifugation was necessary. After extraction and collection of MNPs, the
      analyte ions were eluted using HNO(3) 1.0 mol L(-1). Several factors that may
      affect the preconcentration and extraction process, such as pH, type, and volume
      of eluent, amount of MNPs, sample volume, salting out effect, and interference
      ions were studied and optimized. Under the best experimental conditions,
      linearity was maintained between 0.005-0.5 ng mL(-1). Detection limits for lead
      were 0.8 ng L(-1) based on 3S(b). The relative standard deviation of seven
      replicate measurements of 0.05 ng mL(-1) of Pb(II) ions was 3.8%. Finally, the
      method was successfully applied to extraction and determination of lead ions in
      the water and standard samples.

PMID- 22649301
TI  - Genetic diversity and variability in endangered Pantesco and two other Sicilian
      donkey breeds assessed by microsatellite markers.
AB  - The genetic variability of Pantesco and other two Sicilian autochthonous donkey
      breeds (Ragusano and Grigio Siciliano) was assessed using a set of 14
      microsatellites. The main goals were to describe the current differentiation
      among the breeds and to provide genetic information useful to safeguard the
      Pantesco breed as well as to manage Ragusano and Grigio Siciliano. In the whole
      sample, that included 108 donkeys representative of the three populations, a
      total of 85 alleles were detected. The mean number of alleles was lower in
      Pantesco (3.7), than in Grigio Siciliano and Ragusano (4.4 and 5.9, resp.). The
      three breeds showed a quite low level of gene diversity (He) ranging from 0.471
      in Pantesco to 0.589 in Grigio. The overall genetic differentiation index (Fst)
      was quite high; more than 10% of the diversity was found among breeds. Reynolds'
      (D(R)) genetic distances, correspondence, and population structure analysis
      reproduced the same picture, revealing that, (a) Pantesco breed is the most
      differentiated in the context of the Sicilian indigenous breeds, (b) within
      Ragusano breed, two well-defined subgroups were observed. This information is
      worth of further investigation in order to provide suitable data for conservation
      strategies.

PMID- 22649302
TI  - Psychosocial determinants of attrition in a longitudinal study of tobacco use in
      youth.
AB  - To gain knowledge on psychosocial characteristics that predict the propensity of
      participation in longitudinal studies, attrition was analysed in a cohort of 3020
      adolescents participating in the baseline survey of a longitudinal study with
      repeated followup focusing on adolescents' tobacco use. During the followup
      surveys, the proportion of responders was constantly at or above 90%. There were
      941 adolescents (31.2%) who failed to participate in at least one of the six
      followup surveys. Boys had a fifty percent increased risk of nonparticipation
      compared with girls. Adolescents in families with experience of divorce,
      unemployment, and change of residence had a higher risk of nonparticipation. An
      increasing number of stressful life events during the previous year, uptake of
      tobacco use, number of friends, perceived performance at school, truancy, and
      alcohol use during the last term also independently associated with
      nonparticipation. Diverse psychosocial characteristics are independently
      associated with nonparticipation of youths in longitudinal studies.

PMID- 22649303
TI  - The effect of high concentrations of glufosinate ammonium on the yield components
      of transgenic spring wheat (Triticum aestivum L.) constitutively expressing the
      bar gene.
AB  - We present an experiment done on a bar(+) wheat line treated with 14 different
      concentrations of glufosinate ammonium-an effective component of nonselective
      herbicides-during seed germination in a closed experimental system. Yield
      components as number of spikes per plant, number of grains per spike, thousand
      kernel weight, and yield per plant were thoroughly analysed and statistically
      evaluated after harvesting. We found that a concentration of glufosinate ammonium
      5000 times the lethal dose was not enough to inhibit the germination of
      transgenic plants expressing the bar gene. Extremely high concentrations of
      glufosinate ammonium caused a bushy phenotype, significantly lower numbers of
      grains per spike, and thousand kernel weights. Concerning the productivity, we
      observed that concentrations of glufosinate ammonium 64 times the lethal dose did
      not lead to yield depression. Our results draw attention to the possibilities
      implied in the transgenic approaches.

PMID- 22649304
TI  - Increased yield surplus of vetch-wheat rotations under drought in a Mediterranean
      environment.
AB  - This paper presents results of a plot-scale field experiment aiming at the
      comparative evaluation of agricultural practices and agricultural systems as far
      as their performance in very-low-rainfall conditions is concerned. Wheat was
      seeded after common vetch, treated in three different ways, after fallow or after
      the incorporation of dried sewage sludge or straw. Grain and straw yields and
      grain characteristics were always compared with conventional wheat monoculture
      without any additional organic inputs. Results showed a clear positive effect of
      vetch on next year's wheat yield and an increase in grain protein. Not only did
      the exceptionally dry season mask this effect, but also vetch-wheat systems were
      proved to be more effective in restraining wheat yield reductions, which are
      unavoidable under drought, marking these systems the most promising for improving
      sustainability and stability of rainfed agriculture.

PMID- 22649305
TI  - Apoptosis of epithelial cells and macrophages due to nonpigmented Serratia
      marcescens strains.
AB  - Serratia marcescens strains are opportunistic pathogens that are increasingly
      recognized as a cause of severe nosocomial infections. In this study we observed
      interactions between nonpigmented strains with human epithelial and macrophage
      like cells. The strains revealed hemolytic activity only after the contact of the
      cells with erythrocytes. The contact of the bacteria with the host cells was also
      essential to their cytotoxicity. Moreover, all strains revealed adherence ability
      and were invasive to epithelial cells. Analyses of cellular morphology and DNA
      fragmentation of the HEp-2 and J774 cells exhibited typical features of cells
      undergoing apoptosis. We observed morphological changes, including condensation
      of nuclear chromatin and formation of membrane-bound apoptotic bodies. The lowest
      apoptotic index in HEp-2 cells did not exceed 25%, whereas the highest reached
      59% at 24 h and 72% at 48 h after infection. Most of the strains (60%) induced
      fragmentation of nuclear DNA. The process depended on the activation of caspases,
      and was completely blocked by the pan-caspase inhibitor z-VAD-fmk. This study
      provided new insights into the mechanisms of nonpigmented S. marcescens
      pathogenesis. The results revealed that the strains produce cell-contact toxins
      that facilitate bacterial invasion, induce hemolysis, cytotoxicity, and apoptosis
      of host cells.

PMID- 22649306
TI  - Preparation and characterization of alginate and psyllium beads containing
      Lactobacillus acidophilus.
AB  - This paper describes preparation and characterization of beads of alginate and
      psyllium containing probiotic bacteria of Lactobacillus acidophilus DMSZ20079.
      Twelve different formulations containing alginate (ALG) and alginate-psyllium
      (ALG-PSL) were prepared using extrusion technique. The prepared beads were
      characterized in terms of size, morphology and surface properties, encapsulation
      efficiency, viabilities in acid (pH 1.8, 2 hours) and bile (0.5% w/v, 2 hours)
      conditions, and release in simulated colon pH conditions. The results showed that
      spherical beads with narrow size distribution ranging from 1.59 +/- 0.04 to 1.67
      +/- 0.09 mm for ALG and from 1.61 +/- 0.06 to 1.80 +/- 0.07 mm for ALG-PSL with
      encapsulation efficiency higher than 98% were achieved. Furthermore, addition of
      PSL into ALG enhanced the integrity of prepared beads in comparison with ALG
      formulations. The results indicated that incorporation of PSL into alginate beads
      improved viability of the bacteria in acidic conditions as well as bile
      conditions. Also, stimulating effect of PSL on the probiotic bacteria was
      observed through 20-hour incubation in simulated colonic pH solution. According
      to our in vitro studies, PSL can be a suitable polymer candidate for partial
      substitution with ALG for probiotic coating.

PMID- 22649307
TI  - Development of communication behaviour: receiver ontogeny in Tungara frogs and a
      prospectus for a behavioural evolutionary development.
AB  - Most studies addressing the development of animal communication have focused on
      signal production rather than receiver decoding, and similar emphasis has been
      given to learning over nonlearning. But receivers are an integral part of a
      communication network, and nonlearned mechanisms appear to be more ubiquitous
      than learned ones in the communication systems of most animals. Here we review
      the results of recent experiments and outline future directions for integrative
      studies on the development of a primarily nonlearned behaviour-recognition of
      communication signals during ontogeny in a tropical frog. The results suggest
      that antecedents to adult behaviours might be a common feature of developing
      organisms. Given the essential role that acoustic communication serves in
      reproduction for many organisms and that receivers can exert strong influence on
      the evolution of signals, understanding the evolutionary developmental basis of
      mate recognition will provide new insights into the evolution of communication
      systems.

PMID- 22649308
TI  - Occurrence of Magellanic penguins along the Northeast Brazilian coast during 2008
      Austral winter.
AB  - During the austral winter of 2008, thousands of penguins traveled to low
      latitudes along the South Atlantic coast of South America. The atmospheric and
      oceanic conditions from April to July 2008 may account for the penguins' unusual
      geographic distribution. During that period, South Atlantic coastal waters were
      cooler; the wind anomalies had northward and onshore components; the ocean's
      coastal region presented northward currents that favored the penguins to travel
      toward lower latitudes. This anomalous climate regime resulted from extreme
      meteorological frontal systems that occurred mainly during June 2008. Three
      consecutive extreme midlatitude cyclones produced strong wind shear that resulted
      in the northward oceanic flow along the South American eastern shoreline favoring
      the penguins to be spotted in northern tropical waters.

PMID- 22649309
TI  - Wild termitomyces species collected from Ondo and Ekiti States are more related
      to African species as revealed by ITS region of rDNA.
AB  - Molecular identification of eighteen Termitomyces species collected from two
      states, Ondo and Ekiti in Nigeria was carried out using the internal transcribed
      spacer (ITS) region. The amplicons obtained from rDNA of Termitomyces species
      were compared with existing sequences in the NCBI GenBank. The results of the ITS
      sequence analysis discriminated between all the Termitomyces species (obtained
      from Ondo and Ekiti States) and Termitomyces sp. sequences obtained from NCBI
      GenBank. The degree of similarity of T1 to T18 to gene of Termitomyces sp.
      obtained from NCBI ranges between 82 and 99 percent. Termitomyces species from
      Garbon with ascension number AF321374 was the closest relative of T1 to T18
      except T12 that has T. eurhizus and T. striatus as the closet relative.
      Phylogenetic tree generated with ITS sequences obtained from NCBI GenBank data
      revealed that T1 to T18 are more related to Termitomyces species indigenous to
      African countries such as Senegal, Congo, and Gabon.

PMID- 22649310
TI  - Use of enzymatic bio-Fenton as a new approach in decolorization of malachite
      green.
AB  - An enzymatic reaction using glucose oxidase was applied for in situ production of
      hydrogen peroxide for use in simultaneously Fenton's reaction in decolorization
      of malachite green. It was found that decolorization rate increased by increasing
      of glucose concentration from 0.2 g/L to 1.5 g/L. Decolorization rate showed
      different behaviors versus temperature changes. Initial rate of decolorization
      process was increased by increasing of temperature; after 30 minutes, especially
      at temperatures above 30  degrees C, the decolorization rate was gradually
      reduced. The pH value in the reaction media was decreased from natural to about
      pH = 3 which had synergic effect on the Fenton process by stabilizing of Fe(2+)
      ions.

PMID- 22649311
TI  - NADP-dependent isocitrate dehydrogenase from Arabidopsis roots contributes in the
      mechanism of defence against the nitro-oxidative stress induced by salinity.
AB  - NADPH regeneration appears to be essential in the mechanism of plant defence
      against oxidative stress. Plants contain several NADPH-generating dehydrogenases
      including isocitrate dehydrogenase (NADP-ICDH), glucose-6-phosphate dehydrogenase
      (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and malic enzyme (ME). In
      Arabidopsis seedlings grown under salinity conditions (100 mM NaCl) the analysis
      of physiological parameters, antioxidant enzymes (catalase and superoxide
      dismutase) and content of superoxide radical (O2?-), nitric oxide (NO), and
      peroxynitrite (ONOO(-)) indicates a process of nitro-oxidative stress induced by
      NaCl. Among the analysed NADPH-generating dehydrogenases under salinity
      conditions, the NADP-ICDH showed the maximum activity mainly attributable to the
      root NADP-ICDH. Thus, these data provide new insights on the relevance of the
      NADP-ICDH which could be considered as a second barrier in the mechanism of
      response against the nitro-oxidative stress generated by salinity.

PMID- 22649312
TI  - Blood cell profiles of the tadpoles of the Dubois's tree frog, Polypedates
      teraiensis Dubois, 1986 (Anura: Rhacophoridae).
AB  - The present paper describes a sequential study of the leukocyte profiles and the
      changes in morphometry and morphology of erythrocytes in the tadpoles of
      Polypedates teraiensis during their development and metamorphosis, that is,
      transfer from an aquatic mode to a terrestrial mode of life. Blood smears of 21
      different stages (Gosner stage 26 to 46) of tadpoles were investigated.
      Population of erythrocytes was heterogeneous in population represented by various
      forms (oval, elliptical or rounded cells, comma shaped, teardrop shaped,
      schistocytes, senile erythrocytes, crenulated RBCs). Correlation between various
      morphometric values of erythrocytes was determined with different developing
      stages of tadpoles. Amongst the leucocytes, the lymphocytes were the most
      abundant cells followed by neutrophils. Neutrophils and monocytes showed varied
      morphologic forms. The percentage of lymphocytes and neutrophils showed a
      negative whereas percentage of eosinophil, basophil, and monocytes showed a
      positive correlation with the developmental stages of tadpoles. Blood platelets
      were also observed, which were rounded in shape and found in aggregates.

PMID- 22649314
TI  - Synthesis and neuropharmacological evaluation of some novel quinoxaline 2, 3
      dione derivatives.
AB  - Quinoxaline-2, 3-dione obtained from cyclocondensation reaction of o-phenylene
      diamine with oxalic acid was reacted with three different ketones and
      formaldehyde to give the corresponding Mannich bases in satisfactory yield. Their
      structures were confirmed by using (1)H NMR, IR, and mass analysis. In
      pharmacological evaluation, the synthesized compounds showed its curative effect
      against ethidium-bromide-induced demyelination in rats. For the purpose,
      different screening methods such as open field exploratory behavior test, rota
      rod test, grip strength test, beam walk test, and photo actometer test were
      performed. Ethidium bromide induction showed muscle weakness; muscle
      discoordination; loss of locomotor activity, and so forth, the synthesized drugs
      reversed all the above-mentioned neuromuscular disorders caused by ethidium
      bromide administration.

PMID- 22649313
TI  - Biological effects of weak electromagnetic field on healthy and infected lime
      (Citrus aurantifolia) trees with phytoplasma.
AB  - Exposure to electromagnetic fields (EMF) has become an issue of concern for a
      great many people and is an active area of research. Phytoplasmas, also known as
      mycoplasma-like organisms, are wall-less prokaryotes that are pathogens of many
      plant species throughout the world. Effects of electromagnetic fields on the
      changes of lipid peroxidation, content of H(2)O(2), proline, protein, and
      carbohydrates were investigated in leaves of two-year-old trees of lime (Citrus
      aurantifolia) infected by the Candidatus Phytoplasma aurantifoliae. The healthy
      and infected plants were discontinuously exposed to a 10 KHz quadratic EMF with
      maximum power of 9 W for 5 days, each 5 h, at 25  degrees C. Fresh and dry weight
      of leaves, content of MDA, proline, and protein increased in both healthy and
      infected plants under electromagnetic fields, compared with those of the control
      plants. Electromagnetic fields decreased hydrogen peroxide and carbohydrates
      content in both healthy and infected plants compared to those of the controls.

PMID- 22649315
TI  - Acute effects of vardenafil on pulmonary artery responsiveness in pulmonary
      hypertension.
AB  - Phosphodiesterase type-5 (PDE-5) inhibitors are novel and important options for
      the treatment of pulmonary arterial hypertension (PAH). Therefore, we aimed to
      examine effects of vardenafil, a PDE-5 inhibitor, on the pulmonary arteries
      isolated from rats with monocrotaline- (MCT-) induced pulmonary hypertension. MCT
      (60 mg/kg) or its vehicle was administered by a single intraperitoneal injection
      to 6-week-old male Sprague Dawley rats. Rats were sacrificed 21 days after MCT
      injection, and the main pulmonary arteries were isolated and then mounted in 20
      mL organ baths. Concentration-response curves for vardenafil (10(-10)-10(-5) M)
      were constructed in phenylephrine- (Phe-) precontracted rings. PAH caused marked
      rightward shift in the curves to vardenafil whereas maximal responses were not
      affected. Inhibition of NO synthase (L-NAME, 10(-4) M) or guanylyl cyclase (ODQ,
      10(-5) M) caused similar attenuation in responses evoked by vardenafil. Moreover,
      contraction responses induced by CaCl(2) (3 * 10(-5)-3 * 10(-2) M) were
      significantly reduced in concentration-dependent manner by vardenafil. In
      conclusion, vardenafil induced pulmonary vasodilatation via inhibition of
      extracellular calcium entry in addition to NO-cGMP pathway activation. These
      results provide evidence that impaired arterial relaxation in PAH can be
      prevented by vardenafil. Thus, vardenafil represents a valuable therapeutic
      approach in PAH besides other PDE-5 inhibitors.

PMID- 22649317
TI  - Production response and digestive enzymatic activity of the Pacific white shrimp
      Litopenaeus vannamei (Boone, 1931) intensively pregrown in microbial
      heterotrophic and autotrophic-based systems.
AB  - Shrimp postlarvae were reared into different microcosm systems without water
      exchange; a traditional system based on simple fertilization to improve
      microalgae concentration (control), an autotrophic system (AS) based on the
      promotion of biofloc and biofilm by the addition of fertilizer and artificial
      substrates and a heterotrophic system (HS) based on the promotion of
      heterotrophic bacteria by the addition of nitrogenous and carbonaceous sources
      and artificial substrates. Better growth performance and survival were registered
      in shrimp from the AS and HS compared to the control. Feed conversion ratios were
      below 0.7 for all treatments, but AS and HS were significantly lower than the
      control. Regarding digestive performance, no significant differences were
      observed for trypsin, amylase and lipase activities among AS and control shrimp;
      however, shrimp from HS showed a higher trypsin and amylase activities,
      suggesting a higher digestive activity caused by the presence of microbial
      bioflocs. The presence of biofilm and bioflocs composed by either autotrophic or
      heterotrophic organisms in combination with formulated feed improved the growth
      performance and survival of shrimp. Apparently, such combination fits the
      nutritional requirements of shrimp.

PMID- 22649316
TI  - A study on solubilization of poorly soluble drugs by cyclodextrins and micelles:
      complexation and binding characteristics of sulfamethoxazole and trimethoprim.
AB  - The present study is focused on the characterization of solubilization of poorly
      soluble drugs, that is, sulfamethoxazole (SMX) and trimethoprim (TMP) by
      cyclodextrins (alpha-, beta-, and gamma-CDs) and anionic surfactant sodium
      dodecyl sulfate (SDS). The phase solubility diagrams drawn from UV spectral
      measurements are of the A(L) type and indicate an enhancement of SMX and TMP
      solubility in the presence of CDs. Complex formation tendency of TMP with CDs
      followed the order: gamma-CD > beta-CD > alpha-C. However, the complex formation
      constant values, for SMX-CD system yielded the different affinity and follow the
      order: beta-CD > gamma-CD > alpha-CD. With taking into consideration of
      solubilization capacity of SDS micelles, it has been found that the solubility
      enhancement of TMP is much higher than that of SMX in the presence of SDS
      micelles. The binding constants of SMX and TMP obtained from the Benesi
      Hildebrand equation are also confirmed by the estimated surface properties of
      SDS, employing the surface tension measurements. In order to elucidate the
      solubilization characteristics the surface tension measurements were also
      performed for nonionic surfactant Triton X-100. Polarity of the microenvironment
      and probable location of SMX and TMP were also discussed in the presence of
      various organic solvents.

PMID- 22649318
TI  - Impact of an interleukin-1 receptor antagonist and erythropoietin on experimental
      myocardial ischemia/reperfusion injury.
AB  - BACKGROUND: Revascularization of infarcted myocardium results in release of
      inflammatory cytokines mediating myocardial reperfusion injury and heart failure.
      Blockage of inflammatory pathways dampens myocardial injury and reduces infarct
      size. We compared the impact of the interleukin-1 receptor antagonist Anakinra
      and erythropoietin on myocardial ischemia/reperfusion injury. In contrast to
      others, we hypothesized that drug administration prior to reperfusion reduces
      myocardial damage. METHODS AND RESULTS: 12-15 week-old Lewis rats were subjected
      to myocardial ischemia by a 1 hr occlusion of the left anterior descending
      coronary artery. After 15 min of ischemia, a single shot of Anakinra (2 mg/kg
      body weight (bw)) or erythropoietin (5000 IE/kg bw) was administered
      intravenously. In contrast to erythropoietin, Anakinra decreased infarct size (P
      < 0.05, N = 4/group) and troponin T levels (P < 0.05, N = 4/group). CONCLUSION:
      One-time intravenous administration of Anakinra prior to myocardial reperfusion
      reduces infarct size in experimental ischemia/reperfusion injury. Thus, Anakinra
      may represent a treatment option in myocardial infarction prior to
      revascularization.

PMID- 22649320
TI  - A novel micellar electrokinetic chromatographic method for separation of metal
      DDTC complexes.
AB  - Micellar electrokinetic chromatography (MEKC) was examined for the separation and
      determination of Mo(VI), Cr(VI), Ni(II), Pd(II), and Co(III) as diethyl
      dithiocarbamate (DDTC) chelates. The separation was achieved from fused silica
      capillary (52 cm * 75 MUm id) with effective length 40 cm, background electrolyte
      (BGE) borate buffer pH 9.1 (25 mM), CTAB 30% (100 mM), and 1% butanol in methanol
      (70 : 30 : 5 v/v/v) with applied voltage of -10 kV using reverse polarity. The
      photodiode array detection was achieved at 225 nm. The linear calibration for
      each of the element was obtained within 0.16-10 MUg/mL with a limit of detection
      (LOD) 0.005-0.0167 MUg/mL. The separation and determination was repeatable with
      relative standard deviation (RSD) within 2.4-3.3% (n = 4) in terms of migration
      time and peak height/peak area. The method was applied for the determination of
      Mo(VI) from potatoes and almond, Ni(II) from hydrogenated vegetable oil, and
      Co(III) from pharmaceutical preparations with RSD within 3.9%. The results
      obtained were checked by standard addition and rechecked by atomic absorption
      spectrometry.

PMID- 22649321
TI  - Sensitivity of beech trees to global environmental changes at most north-eastern
      latitude of their occurrence in Europe.
AB  - The present study aimed to detect sensitivity of beech trees (Fagus sylvatica L.)
      to meteorological parameters and air pollution by acidifying species as well as
      to surface ozone outside their north-eastern distribution range. Data set since
      1981 of Preila EMEP station enabled to establish that hot Summers, cold dormant,
      and dry and cold first-half of vegetation periods resulted in beech tree growth
      reduction. These meteorological parameters explained 57% variation in beech tree
      ring widths. Acidifying species had no significant effect on beech tree growth.
      Only ozone was among key factors contributing to beech stand productivity.
      Phytotoxic effect of this pollutant increased explanation rate of beech tree ring
      variation by 18%, that is, up to 75%. However, due to climate changes the warmer
      dormant periods alone are not the basis ensuring favourable conditions for beech
      tree growth. Increase in air temperature in June-August and decrease in
      precipitation amount in the first half of vegetation period should result in
      beech tree radial increment reduction. Despite the fact that phytotoxic effect of
      surface ozone should not increase due to stabilization in its concentration, it
      is rather problematic to expect better environmental conditions for beech tree
      growth at northern latitude of their pervasion.

PMID- 22649319
TI  - Oxidative stress and heart failure in altered thyroid States.
AB  - Increased or reduced action of thyroid hormone on certain molecular pathways in
      the heart and vasculature causes relevant cardiovascular derangements. It is well
      established that hyperthyroidism induces a hyperdynamic cardiovascular state,
      which is associated with a faster heart rate, enhanced left ventricular systolic
      and diastolic function whereas hypothyroidism is characterized by the opposite
      changes. Hyperthyroidism and hypothyroidism represent opposite clinical
      conditions, albeit not mirror images. Recent experimental and clinical studies
      have suggested the involvement of ROS tissue damage under altered thyroid status.
      Altered-thyroid state-linked changes in heart modify their susceptibility to
      oxidants and the extent of the oxidative damage they suffer following oxidative
      challenge. Chronic increase in the cellular levels of ROS can lead to a
      catastrophic cycle of DNA damage, mitochondrial dysfunction, further ROS
      generation and cellular injury. Thus, these cellular events might play an
      important role in the development and progression of myocardial remodeling and
      heart failure in altered thyroid states (hypo- and hyper-thyroidism). The present
      review aims at elucidating the various signaling pathways mediated via ROS and
      their modulation under altered thyroid state and the possibility of antioxidant
      therapy.

PMID- 22649322
TI  - Self-determination as a psychological and positive youth development construct.
AB  - This paper presents a review of self-determination as a positive youth
      development construct. The definition and conceptualization of the concept are
      examined from the perspective of self-determination theory and the functional
      theory of self-determination. Theories of self-determination from the perspective
      of motivation and skills enhancement are examined. Factors contributing to self
      determination, such as autonomy-supportive teaching and parenting style, culture,
      efficacy of intervention programmes, and the educational benefits of self
      determination for students, are discussed. Strategies to promote self
      determination in an educational context and implications for further research and
      practice are discussed.

PMID- 22649323
TI  - Prosocial involvement as a positive youth development construct: a conceptual
      review.
AB  - This paper discusses the concept of prosocial involvement as a positive youth
      development construct. How prosocial involvement is defined and how the different
      theories conceptualize prosocial involvement are reviewed. Antecedents of
      prosocial involvement such as biological traits, personality, cognitive and
      emotional processes, socialization experience, culture, and their social context
      are examined. The relationship between prosocial involvement and adolescent
      developmental outcomes, together with strategies to promote prosocial involvement
      in adolescents, are discussed. Finally, directions for future research and
      practice are proposed.

PMID- 22649324
TI  - Proteomic analysis of Bacillus thuringiensis strain 4.0718 at different growth
      phases.
AB  - The growth process of Bacillus thuringiensis Bt4.0718 strain was studied using
      proteomic technologies. The proteins of Bt whole cells at three phases-middle
      vegetative, early sporulation, and late sporulation-were extracted with lysis
      buffer, followed with separation by 2-DE and identified by MALDI-TOF/TOF MS.
      Bioactive factors such as insecticidal crystal proteins (ICPs) including
      Cry1Ac(3), Cry2Aa, and BTRX28, immune inhibitor (InhA), and InhA precursor were
      identified. InhA started to express at the middle vegetative phase, suggesting
      its contribution to the survival of Bt in the host body. At the early sporulation
      phase, ICPs started their expression. CotJC, OppA, ORF1, and SpoIVA related to
      the formation of crystals and spores were identified, the expression
      characteristics of which ensured the stable formation of crystals and spores.
      This study provides an important foundation for further exploration of the stable
      expression of ICPs, the smooth formation of crystals, and the construction of
      recombinant strains.

PMID- 22649325
TI  - Regulating drug release behavior and kinetics from matrix tablets based on fine
      particle-sized ethyl cellulose ether derivatives: an in vitro and in vivo
      evaluation.
AB  - The design and fabrication of sustained/controlled release dosage forms,
      employing new excipients capable of extending/controlling the release of drugs
      from the dosage forms over prolonged periods, has worked well in achieving
      optimally enhanced therapeutic levels of the drugs. In this sense, the objective
      of this study was to investigate the suitability of selected cellulose ether
      derivatives for use in direct compression (DC) and as efficient drug release
      controlling agents. Controlled release matrix tablets of ciprofloxacin were
      prepared at different drug-to-polymer (D : P) ratios by direct compression using
      a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium
      7FP) as rate controlling polymer. The tablets obtained were evaluated for various
      physico-chemical characteristics and in-vitro drug release studies were conducted
      in phosphate buffer (pH 7.4) using PharmaTest dissolution apparatus at constant
      temperature of 37  degrees C +/- 0.1. Similarity factor f(2) was employed to the
      release profiles of test formulations and were compared with marketed
      ciprofloxacin conventional tablets. Drug release mechanism and the kinetics
      involved were investigated by fitting the release profile data to various kinetic
      models. It was found that with increasing the proportion of ethylcellulose ether
      derivative in the matrix, the drug release was significantly extended up to 24
      hours. The tablets exhibited zero order or nearly zero order drug transport
      mechanism. In vivo drug release performance of the developed controlled release
      tablets and reference conventional tablets containing ciprofloxacin were
      determined in rabbit serum according to randomized two-way crossover study design
      using High Performance Liquid Chromatography. Several bioavailability parameters
      of both the test tablets and conventional tablets including C(max?), T(max?) and
      AUC(0-t) were compared which showed an optimized C(max?) and T(max?) (P < 0.05).
      A good correlation was obtained between in vitro drug release and in vivo drug
      absorption with correlation value (R(2) = 0.934). Relative bioavailability was
      found to be 93%. Reproducibility of manufacturing process and accelerated
      stability of the developed tablets were performed in stability chamber at 40 +/-
      2 degrees C and 75 +/- 5% relative humidity for a period of 6 months and were
      found to be stable throughout the stability period.

PMID- 22649326
TI  - Eutectic salt catalyzed environmentally benign and highly efficient Biginelli
      reaction.
AB  - A simple deep eutectic solvent based on tin (II) chloride was used as a dual
      catalyst and environmentally benign reaction medium for an efficient synthesis of
      3,4-dihydropyrimidin-2(1H)-one derivatives, from aromatic and aliphatic
      aldehydes, 1,3-dicarbonyl compounds, and urea in good-to-excellent yields and
      short reaction time. This simple ammonium deep eutectic solvent, easily
      synthesized from choline chloride and tin chloride, is relatively inexpensive and
      recyclable, making it applicable for industrial applications.

PMID- 22649327
TI  - Lymph node harvest in Dukes' A cancer pathologist may need to consider fat
      dissolving technique: an observational study.
AB  - BACKGROUND: National institute of clinical excellence (NICE) recommends that a
      median of 12 lymph nodes be examined in patients operated on with curative intent
      to- treat colorectal cancer (CRC). Patients with lymph node harvest less than
      this may be considered under staged and may receive adjuvant chemotherapy. The
      aim of our study was to ascertain median number of lymph nodes examined in early
      colorectal cancers. METHOD: Patients undergoing colorectal resection between June
      2007 and May 2008 were identified and pathological staging obtained using
      pathology database. RESULTS: 146 patients underwent standardised laparoscopic or
      open resection of colorectal cancers during this period. Overall median number of
      lymph nodes harvested/patient was 14 (3-40). When analysed by stage, median
      number of lymph nodes harvested in Dukes' A, B, and C cancers was 10, 14, and 15,
      respectively. 11/18 (61%) patients with Dukes' A carcinoma had lymph node harvest
      of less than 12 compared with 15/55 (27%) patients with Dukes' B. CONCLUSION:
      Lymph node harvest in Dukes' A cancers using standard techniques tends to be low.
      Pathologists may have to consider special techniques in harvesting lymph nodes
      for early colorectal cancers.

PMID- 22649328
TI  - Mycoflora and natural incidence of selected mycotoxins in rabbit and Chinchilla
      feeds.
AB  - Mycotoxins are secondary metabolites produced by filamentous fungi that cause a
      toxic response when ingested by animals or man. Demand of natural fur, such as
      those from rabbit and chinchilla, produced under controlled conditions, has
      increased worldwide. The toxicogenic mycoflora contaminating feeds for these
      animals was enumerated and identified. Six of the major mycotoxins implicated in
      animal mycotoxicosis were detected and quantified. Moulds count ranged from <10
      to 4.7 * 10(5) CFU g(-1); 14% of the samples exceeded the limit that determines
      hygienic feed quality. More than twenty species belonging to the five most
      important mycotoxigenic mould genera were recovered. Among the analyzed
      mycotoxins, aflatoxins were recovered in 100% of the examined samples,
      deoxynivalenol in 95%, fumonisins in 100%, ochratoxin A in 98%, T2 toxin in 98%,
      and zearalenone in 100%. Cooccurrence of mycotoxins was observed in 100% of the
      samples analyzed. Exposure to multiple mycotoxins was thus demonstrated for these
      animals.

PMID- 22649330
TI  - News from the San Antonio Breast Cancer Symposium 2009.

PMID- 22649329
TI  - Polycyclic aromatic hydrocarbons bound to PM 2.5 in urban Coimbatore, India with
      emphasis on source apportionment.
AB  - Coimbatore is one of the fast growing industrial cities of Southern India with an
      urban population of 1.9 million. This study attempts to evaluate the trends of
      airborne fine particulates (PM 2.5) and polyaromatic hydrocarbons (PAH) on them.
      The PM 2.5 mass was collected in polytetra fluoroethylene filters using fine
      particulate sampler at monthly intervals during March 2009 to February 2010. PAHs
      were extracted from PM 2.5 and estimated by high-performance liquid
      chromatography. It is alarming to note that PM 2.5 values ranged between 27.85
      and 165.75 MUg/m(3) and exceeded the air quality standards in many sampling
      events. The sum of 9 PAHs bound to PM 2.5 in a single sampling event ranged from
      4.1 to 1632.3 ng/m(3). PAH diagnostic ratios and principal component analysis
      results revealed vehicular emissions and diesel-powered generators as predominant
      sources of PAH in Coimbatore.

PMID- 22649331
TI  - Liver Transplantation because of Acute Liver Failure due to Heme Arginate
      Overdose in a Patient with Acute Intermittent Porphyria.
AB  - In acute attacks of acute intermittent porphyria, the mainstay of treatment is
      glucose and heme arginate administration. We present the case of a 58-year-old
      patient with acute liver failure requiring urgent liver transplantation after
      erroneous 6-fold overdose of heme arginate during an acute attack. As recommended
      in the product information, albumin and charcoal were administered and
      hemodiafiltration was started, which could not prevent acute liver failure,
      requiring super-urgent liver transplantation after 6 days. The explanted liver
      showed no preexisting liver cirrhosis, but signs of subacute liver injury and
      starting regeneration. The patient recovered within a short time. A literature
      review revealed four poorly documented cases of potential hepatic and/or renal
      toxicity of hematin or heme arginate. This is the first published case report of
      acute liver failure requiring super-urgent liver transplantation after accidental
      heme arginate overdose. The literature and recommendations in case of heme
      arginate overdose are summarized. Knowledge of a potentially fatal course is
      important for the management of future cases. If acute liver failure in case of
      heme arginate overdose is progressive, super-urgent liver transplantation has to
      be evaluated.

PMID- 22649332
TI  - Iatrogenic Complications in Five Patients with Upper Gastrointestinal Bleeding
      due to Ambient Air: Case Series and Literature Review.
AB  - Despite the increasing use of carbon dioxide for endoscopies during the last
      years, ambient air is still used. The amount of air depends on several factors
      such as examination time, presumable diameter of the endoscope channel and of
      course active use of air by the operator. Although endoscopic complications due
      to ambient air in the gastrointestinal (GI) tract are a rare observation and
      mostly described in the colon, we report five cases in the upper GI tract due to
      insufflating large amounts of air through the endoscopes. All 5 patients needed
      an emergency upper endoscopy for acute presumed upper GI bleeding. In two cases
      both esophageal variceal bleeding and ulcer bleeding were detected; the fifth
      case presented with a bleeding due to gastric cancer. Due to insufflation of
      inadequate amounts of air through the endoscope channel, all patients
      deteriorated in circulation and ventilation. Two rumenocenteses and consecutively
      three laparotomies had to be performed in three patients. In the other two,
      gastroscopies had to be stopped for an emergency computed tomography. All
      critical incidents were believed to be a consequence of a long-lasting
      examination with use of too much air. Therefore in emergency situations,
      endoscopies should be performed with either submersion, low air flow pumps or
      even better by the use of carbon dioxide.

PMID- 22649333
TI  - Prolonged survival in a patient with neuroendocrine tumor of the cecum and
      diffuse peritoneal carcinomatosis.
AB  - Peritoneal carcinomatosis is a well-known factor of poor prognosis in patients
      with digestive adenocarcinomas. Peritoneal dissemination may also occur in midgut
      well-differentiated neuroendocrine tumors, but its influence on survival is ill
      defined. We report here the history of a 64-year-old woman who had a
      neuroendocrine tumor of the cecum with multiple synchronous metastases in the
      liver and diffuse peritoneal carcinomatosis. She underwent surgical resection of
      the primary tumor and cytoreduction of liver metastases, and received
      subsequently chemotherapy and somatostatin analogs. In spite of the widespread
      extension of the disease, she survived for 13 years and died from a carcinoid
      heart disease. We discuss the natural history and prognostic factors in patients
      with midgut well-differentiated neuroendocrine tumors, with a focus on the impact
      of the peritoneal carcinomatosis.

PMID- 22649334
TI  - Diagnostic Dilemma in a Patient with Jaundice: How to Differentiate between
      Autoimmune Pancreatitis, Primary Sclerosing Cholangitis and Pancreas Carcinoma.
AB  - A 68-year-old male patient was referred to our institution in May 2011 for a
      suspected tumor in the pancreatic head with consecutive jaundice. Using magnetic
      resonance imaging, further differentiation between chronic inflammation and a
      malignant process was not possible with certainty. Apart from cholestasis,
      laboratory studies showed increased values for CA 19-9 to 532 U/ml (normal <37
      U/ml) and hypergammaglobulinemia (immunoglobulin G, IgG) of 19.3% (normal 8.0
      15.8%) with an elevation of the IgG4 subtype to 2,350 mg/l (normal 52-1,250
      mg/l). Endoscopic retrograde cholangiopancreatography revealed a prominent
      stenosis of the distal ductus hepaticus communis caused by pancreatic head
      swelling and also a bihilar stenosis of the main hepatic bile ducts. Cytology
      demonstrated inflammatory cells without evidence of malignancy. Under suspicion
      of autoimmune pancreatitis with IgG4-associated cholangitis, immunosuppressive
      therapy with steroids and azathioprine was started. Follow-up endoscopic
      retrograde cholangiopancreatography after 3 months displayed regressive
      development of the diverse stenoses. Jaundice had disappeared and blood values
      had returned to normal ranges. Moreover, no tumor of the pancreatic head was
      present in the magnetic resonance control images. Due to clinical and
      radiological similarities but a consecutive completely different prognosis and
      therapy, it is of fundamental importance to differentiate between pancreatic
      cancer and autoimmune pancreatitis. Especially, determination of serum IgG4
      levels and associated bile duct lesions induced by inflammation should clarify
      the diagnosis of autoimmune pancreatitis and legitimate immunosuppressive
      therapy.

PMID- 22649335
TI  - Autoimmunity-related granulomatous dermatitis in association with hepatitis.
AB  - AIM: Both interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic
      granulomatous dermatitis (PNGD) are rare disorders typically associated with
      systemic autoimmune conditions. They probably represent different aspects of a
      disease spectrum encompassing the concept of autoimmunity-related granulomatous
      dermatitis (ARGD). CASE REPORT: A 61-year-old woman presented with ARGD and
      autoimmune hepatitis. The clinical presentation suggested PNGD, while
      histopathology was consistent with IGD. DISCUSSION: The association of ARGD with
      autoimmune hepatitis is apparently a rare event. The present case shows that the
      clinicopathological correlation in ARGD does not always clearly fit with the
      classical presentations of IGD or PNGD.

PMID- 22649336
TI  - A case of generalized acanthosis nigricans with positive lupus erythematosus
      related autoantibodies and antimicrosomal antibody: autoimmune acanthosis
      nigricans?
AB  - Acanthosis nigricans (AN) is a hyperpigmented keratotic skin lesion known to be
      associated with malignant disease and endocrinopathy. We report a very rare case
      of generalized AN with Sjogren's syndrome- and systemic lupus erythematosus-like
      features but without type B insulin resistance. Neither internal malignancy nor
      other endocrinological disorders, including glucose intolerance, were detected
      during a 10-year clinical course with benign diffuse papillomatosis extending
      from the mucosa of the larynx to the esophagogastric junction. The case was
      complicated with chronic thyroiditis and interstitial pneumonia, which were not
      treated with any medication. AN skin lesions and mucosal papillomatosis regressed
      with oral cyclosporine A, accompanied by the lowering of autoantibody titers.
      This is the first report of generalized AN involving an area from the mucosa of
      the larynx to the esophagogastric junction accompanied by autoimmune
      manifestations which responded to systemic immunosuppressive therapy.

PMID- 22649337
TI  - Recurrence of mycosis fungoides on multiple melanocytic nevi: a case report and
      review of the literature.
AB  - Melanocytic nevi represent a widespread cutaneous finding. Nevertheless, the
      presence of mycosis fungoides and melanocytic nevi in the same location is an
      extremely rare event. We report the case of a patient affected by mycosis
      fungoides and treated with PUVA therapy, with complete remission of the disease.
      Eight years after therapy discontinuation, he presented epidermal scaling and an
      erythematous perinevic halo on 3 old melanocytic lesions, the clinical aspect of
      which was highly suggestive for Meyerson nevi. The histological and
      immunohistochemical examination of an excised melanocytic lesion revealed
      histological features consistent with the diagnosis of mycosis fungoides
      superimposed on junctional melanocytic nevi. The finding of patches of mycosis
      fungoides superimposed on melanocytic nevi is a rare event; the confounding
      clinical appearance with eczematous changes around a pre-existing nevus may
      recall the halo dermatitis known as Meyerson phenomenon; this highlights the
      importance of clinical and histological examination to make the correct diagnosis
      of dermatological diseases.

PMID- 22649338
TI  - A case of syringomatous adenoma of the nipple.
AB  - Syringomatous adenoma of the nipple (SAN) is an extremely rare disease
      originating in the adnexal gland; it was first reported by Rosen in 1983 [Am J
      Surg Pathol 1983;7:739-745]. Since then, 34 cases have been reported worldwide.
      We present the case of a 51-year-old man with SAN, in whom local excision of the
      tumor was performed. Histologically, the tumor consisted of tubules, ductules and
      epithelial cell strands, and most of the proliferating ducts presented with a
      characteristic teardrop or comma-shaped appearance.

PMID- 22649339
TI  - Carcinomatous pericarditis in 3 breast cancer patients with long-term survival.
AB  - With advances in drug treatment of breast cancer, the number of patients
      experiencing cardiac toxicity or carcinomatous pericarditis is expected to
      increase. These conditions can cause cardiac tamponade, which is a potentially
      fatal condition requiring prompt diagnosis and treatment. We experienced 3 breast
      cancer patients with cardiac tamponade due to carcinomatous pericarditis who
      survived for prolonged periods after treatment with pericardiocentesis and
      intrapericardial instillation. The 3 women were 68, 46 and 46 years old,
      respectively, and receiving treatment for recurrent breast cancer after surgery.
      They developed dyspnea and cough and were diagnosed with cardiac tamponade by
      echocardiography. Pericardiocentesis was performed, and cytology of the effusion
      confirmed the diagnosis of carcinomatous pericarditis. Intrapericardial
      instillation of cisplatin reduced the cardiac effusion, ameliorating symptoms.
      The patients died 13, 31 and 14 months later, respectively. In our clinical
      review of 13 other cases of cardiac tamponade due to breast cancer, 85% achieved
      local control after the aforementioned local treatments, which were considered to
      be effective. Although the overall prognosis was poor with a median survival time
      of only 4 months, some patients were able to survive more than 1 year after local
      treatment with subsequent systemic therapy.

PMID- 22649341
TI  - Fulminant adenocarcinoma of the rectum with hepatic metastasis in a young
      pregnant woman: a case report.
AB  - Cancer is the second leading cause of death during the reproductive years, but
      the incidence during pregnancy is low. The incidence of cancer of the rectum
      during pregnancy is very rare (1:50,000 to 1:100,000 pregnancies). Usually, the
      symptoms of this type of cancer are nonspecific and sometimes they are confused
      with normal changes of pregnancy. The diagnosis of rectal cancer is usually made
      in the late stage of pregnancy. The treatment of this cancer involves surgery,
      chemotherapy and radiotherapy, but each type of treatment involves risks to the
      fetus and the pregnant woman. We present a case of a young primiparous woman who
      had a quick and bad evolution of an adenocarcinoma of the rectum diagnosed during
      pregnancy. This patient had extensive involvement of the liver with metastasis
      and she died two weeks after diagnosis. In this case, we present the clinical,
      radiological and pathology findings of this disease.

PMID- 22649340
TI  - Cardiac recurrence in a patient with long-term survival from metastatic colon
      cancer.
AB  - Metastatic colorectal cancer represents a major health problem in the US and
      worldwide. Forty percent of patients undergoing resection of the primary tumor
      will experience relapse. In this brief review, we describe a case of a woman with
      metastatic disease and long-term survival culminating with an unusual myocardial
      recurrence. Over three decades, a multimodality approach has evolved to allow for
      long-term survival in selected patients with metastatic colorectal cancer. In
      this case report, the role of multiple aggressive surgical resections is
      emphasized.

PMID- 22649342
TI  - A case of relapsing-remitting neuroborreliosis? Challenges in the differential
      diagnosis of recurrent myelitis.
AB  - We report the case of a 31-year-old woman with 4 episodes of myelitis with
      pleocytosis, a positive Borrelia burgdorferi serology with positive antibody
      indices, and full recovery each time after antibiotic and steroid treatment,
      suggesting neuroborreliosis. We nevertheless believe that recurrent
      neuroborreliosis is improbable based on the levels of the chemokine CXCL13 in
      cerebrospinal fluid and favor the diagnosis of post-infectious autoimmune
      mediated transverse myelitis possibly triggered by an initial neuroborreliosis as
      the cause of the relapses observed in our patient. We demonstrate the diagnostic
      steps and procedures which were important in the differential diagnosis of this
      unusual and challenging case.

PMID- 22649343
TI  - Confabulations after bilateral consecutive strokes of the lenticulostriate
      arteries.
AB  - We describe the case of a 75-year-old woman who manifested persistent
      confabulations after two consecutive strokes encompassing the area of the
      lenticulostriate arteries territory on both hemispheres. Findings reported on
      this rare clinical syndrome suggest that fantastic confabulations and delusional
      thoughts may arise after bilateral damage of subcortical nonthalamic structures.

PMID- 22649344
TI  - Incidental MRI findings of acute gadolinium hypersensitivity.
AB  - A 13-year-old girl with a remote history of juvenile pilocytic astrocytoma
      developed acute onset flushing, tachycardia and shortness of breath immediately
      following administration of gadopentetate dimeglumine during routine brain MRI
      that subsided following intravenous diphenhydramine. A retrospective review of
      the MRI results revealed multiple areas of contrast enhancement of the face,
      consistent with observed urticaria. The patient received pretreatment medications
      prior to subsequent gadolinium injections without incident. Gadolinium allergy is
      extremely rare and has been reported in less than 0.1% of injections. However, in
      patients who undergo anesthesia for MRI studies, similar subtle extracranial MRI
      findings should alert the neuroradiologist to possible gadolinium allergy that
      may warrant premedication prior to future injections.

PMID- 22649345
TI  - A case of paraneoplastic demyelinating motor polyneuropathy.
AB  - Peripheral neuropathy is commonly accompanied by cancer but demyelinating ones
      are not commonly reported. We report the clinical, neurophysiological, and
      biological characteristics of an 82-year-old patient who presented with a
      demyelinating motor neuropathy and high titre of anti-ganglioside antibodies
      associated with oesophageal cancer. The neurological course worsened rapidly
      despite immunotherapy, leading to a bedridden status. We propose to suspect a
      paraneoplastic origin in older patients or when the clinical course progresses
      rapidly within a few weeks or months.

PMID- 22649346
TI  - A rare case of occipital stroke as a consequence of nonbacterial thrombotic
      endocarditis in ovarian clear cell carcinoma: a case report.
AB  - Hypercoagulability occurs in 15% of patients with malignancy and represents a
      clinical spectrum ranging from abnormal coagulation tests but no clinically
      evident thromboembolic disease, to arterial and venous thrombosis, migratory
      thrombophlebitis, nonbacterial thrombotic endocarditis (NBTE) and disseminated
      intravascular coagulation. The combination of increased procoagulant activity and
      decreased fibrinolytic activity accelerates the prothrombotic potential of
      endothelial cells in malignancy. NBTE is a rare manifestation of cancer-induced
      hypercoagulability and is commonly seen with mucin-producing adenocarcinomas, but
      rarely seen with ovarian clear cell carcinoma (OCCC). Cerebrovascular
      embolization ranges from 14-91% in NBTE. We report a rare case of a 62-year-old
      female presenting with occipital stroke as a consequence of NBTE in OCCC.
      Association of NBTE in OCCC has only been reported in 2 cases so far, but
      presentation with stroke has never been reported in the literature.

PMID- 22649347
TI  - Combination of intravitreal ranibizumab and laser photocoagulation for aggressive
      posterior retinopathy of prematurity.
AB  - PURPOSE: To report on 2 cases of aggressive posterior retinopathy of prematurity
      (ROP) treated with intravitreal ranibizumab (Lucentis((r))) and laser
      photocoagulation. METHODS: Two premature females, born at 25 and 26 weeks'
      gestation with a birth weight of 530 and 550 g, respectively, with aggressive
      posterior ROP received combined treatment with laser photocoagulation and
      intravitreal ranibizumab (0.3 mg [30 ul]) to each eye. Structural outcomes were
      evaluated by indirect ophthalmoscopy and documented by retinography. RESULTS: An
      intravitreal injection was made at 34 weeks of postmenstrual age in the first
      case, followed by laser photocoagulation 1 week later. There was a partial
      regression of ROP with treatment. Five weeks later, neovascularization regrowth
      with bleeding in both eyes (intraretinal and subhyaloid) occurred and retreatment
      with combined therapy was performed. In the second case, single therapy with
      laser photocoagulation was made at 34 weeks of postmenstrual age. In spite of the
      confluent photocoagulation in the avascular area, progression to 4A ROP stage
      occurred 1 week later. Both eyes were retreated 1 week later with intravitreal
      ranibizumab and laser photocoagulation. Treatment resulted in ROP regression in
      both cases. There were no signs of systemic or ocular adverse side effects.
      CONCLUSION: The cases presented show that combination therapy of indirect laser
      photocoagulation and intravitreal ranibizumab can be effective in the management
      of aggressive posterior ROP. Further investigation on anti-VEGF safety in
      premature infants is necessary. Additional studies are needed to define the role
      of anti-VEGF in ROP treatment.

PMID- 22649348
TI  - Macular hypoplasia in congenital disorder of glycosylation type ia.
AB  - Congenital disorders of glycosylation are a rare group of metabolic disorders
      that can result in multiorgan disease. This article describes a novel finding of
      macular hypoplasia in congenital disorders of glycosylation type Ia.

PMID- 22649349
TI  - A rare presentation of conjunctival myxoma with pain and redness: case report and
      literature review.
AB  - BACKGROUND: Conjunctival myxoma is a type of rare, benign tumor of mesenchymal
      cells, with fewer than 30 reported cases in the English literature. It is mostly
      an isolated occurrence but can sometimes be associated with systemic diseases
      such as Carney complex or Zollinger-Ellison syndrome. It is necessary in clinical
      practice to differentiate it from other similar lesions, such as amelanotic
      nevus, lymphangioma, myxoid liposarcoma, spindle-cell lipoma, myxoid
      neurofibroma, and rhabdomyosarcoma. CASE PRESENTATION: The usual presentation of
      conjunctival myxoma is a translucent, well-circumscribed, and painless
      conjunctival mass, but in this report we discuss an unusual case of conjunctival
      myxoma in a 47-year-old Taiwanese woman who presented initially with pain and
      redness. This atypical presentation complicated the diagnosis and the management
      at first. Surgical excision of the mass was performed. The mass was found to be a
      conjunctival myxoma. The patient subsequently underwent extensive evaluation but
      was found not to have any systemic diseases with known association with
      conjunctival myxoma. CONCLUSIONS: In summary, we present a case of conjunctival
      myxoma in a 47-year-old Taiwanese woman. The initial presentation with pain and
      redness was atypical for conjunctival myxoma. The lesion was successfully managed
      with complete excisional biopsy.

PMID- 22649350
TI  - Endocrinology of aging: the convergence of reductionist science with systems
      biology and integrative medicine.

PMID- 22649352
TI  - Epigenetic changes predisposing to type 2 diabetes in intrauterine growth
      retardation.
AB  - Epidemiologic studies have demonstrated an association between intrauterine
      growth retardation and a greater risk of chronic disease, including coronary
      heart disease, hypertension, stroke, and type 2 diabetes in adulthood. An adverse
      intrauterine environment may affect both growth and development of the organism,
      permanently programming endocrine and metabolic functions. One of the mechanisms
      of programming is the epigenetic modification of gene promoters involved in the
      control of key metabolic pathways. The aim of this review is to provide an
      overview of the experimental evidence showing the effects of early exposure to
      suboptimal environment on epigenome. The knowledge of the epigenetic markers of
      programming may allow the identification of susceptible individuals and the
      design of targeted prevention strategies.

PMID- 22649353
TI  - Grand challenges in bone endocrinology.

PMID- 22649354
TI  - Thyroiditis, secondary to viral infection.

PMID- 22649355
TI  - Challenges in endocrinology: moving from the post-genomic era, into the nano
      world and beyond.

PMID- 22649351
TI  - About a snail, a toad, and rodents: animal models for adaptation research.
AB  - Neural adaptation mechanisms have many similarities throughout the animal
      kingdom, enabling to study fundamentals of human adaptation in selected animal
      models with experimental approaches that are impossible to apply in man. This
      will be illustrated by reviewing research on three of such animal models, viz.
      (1) the egg-laying behavior of a snail, Lymnaea stagnalis: how one neuron type
      controls behavior, (2) adaptation to the ambient light condition by a toad,
      Xenopus laevis: how a neuroendocrine cell integrates complex external and neural
      inputs, and (3) stress, feeding, and depression in rodents: how a neuronal
      network co-ordinates different but related complex behaviors. Special attention
      is being paid to the actions of neurochemical messengers, such as neuropeptide Y,
      urocortin 1, and brain-derived neurotrophic factor. While awaiting new
      technological developments to study the living human brain at the cellular and
      molecular levels, continuing progress in the insight in the functioning of human
      adaptation mechanisms may be expected from neuroendocrine research using
      invertebrate and vertebrate animal models.

PMID- 22649356
TI  - Rab proteins and the secretory pathway: the case of rab18 in neuroendocrine
      cells.
AB  - The secretory pathway is a process characteristic of cells specialized in
      secretion such as endocrine cells and neurons. It consists of different stages
      that are dependent on specific transport of proteins in vesicular-tubular
      carriers. Biochemical analyses have unveiled a number of protein families that
      confer identity to carrier vesicles and specificity to their transport. Among
      them is the family of Rab proteins, Ras-like small GTPases that anchor to the
      surface of transport vesicles and participate in vesicle formation from the donor
      compartment, transport along cytoskeletal tracks, and docking and fusion with the
      acceptor compartment. All of these functions are accomplished through the
      recruitment of effector proteins, such as sorting adaptors, tethering factors,
      kinases, phosphatases, and motors. The numerous Rab proteins have distinct
      subcellular distributions throughout the endomembrane system, which ensures
      efficient cargo transfer. Rab proteins act as molecular switches that alternate
      between a cytosolic GDP-bound, inactive form and a membrane-associated GTP-bound,
      active conformation. Cycling between inactive and active states is a highly
      regulated process that enables Rabs to confer spatio-temporal precision to the
      different stages through which a vesicle passes during its lifespan. This review
      focuses on our current knowledge on Rab functioning, from their structural
      features to the multiple regulatory proteins and effectors that control Rab
      activity and translate Rab function. Furthermore, we also summarize the
      information available on a particular Rab protein, Rab18, which has been linked
      to the control of secretory granule traffic in neuroendocrine cells.

PMID- 22649358
TI  - Regulation of placental calcium transport and offspring bone health.
AB  - Osteoporosis causes considerable morbidity and mortality in later life, and the
      risk of the disease is strongly determined by peak bone mass, which is achieved
      in early adulthood. Poor intrauterine and early childhood growth are associated
      with reduced peak bone mass, and increased risk of osteoporotic fracture in older
      age. In this review we describe the regulatory aspects of intrauterine bone
      development, and then summarize the evidence relating early growth to later
      fracture risk. Physiological systems include vitamin D, parathyroid hormone,
      leptin, GH/IGF-1; finally the potential role of epigenetic processes in the
      underlying mechanisms will be explored. Thus factors such as maternal lifestyle,
      diet, body build, physical activity, and vitamin D status in pregnancy all appear
      to influence offspring bone mineral accrual. These data demonstrate a likely
      interaction between environmental factors and gene expression, a phenomenon
      ubiquitous in the natural world (developmental plasticity), as the potential key
      process. Intervention studies are now required to test the hypotheses generated
      by these epidemiological and physiological findings, to inform potential novel
      public health interventions aimed at improving childhood bone health and reducing
      the burden of osteoporotic fracture in future generations.

PMID- 22649357
TI  - Biological Significance of GPCR Heteromerization in the Neuro-Endocrine System.
AB  - Clustering of proteins in higher order complexes is a common theme in biology and
      profoundly influences protein function. The idea that seven-transmembrane
      spanning G protein-coupled receptors (GPCRs) might form dimers or higher order
      oligomeric complexes has been formulated more than 20 years ago. Since then, this
      phenomenon has been investigated with many different biochemical and biophysical
      techniques. The more recent notion of GPCR heteromerization describes the
      specific association of two different GPCRs. GPCR heteromerization may be of
      primary importance in neuroendocrinology, as this may explain at least some of
      the functional crosstalks described between different hormonal systems.
      Importantly, many GPCR heteromers have distinct functional properties compared to
      their corresponding homomers. Heteromer-specific pharmacological profiles might
      be exploited for drug design and open new therapeutic options. GPCR
      heteromerization has been first studied in heterologous expression systems.
      Today, increasing evidence for the existence of GPCR heteromers in endogenous
      systems is emerging providing crucial evidence for the physiological function of
      GPCR heteromerization.

PMID- 22649360
TI  - Thyroid hormones and mesotherapy.

PMID- 22649359
TI  - FTO Biology and Obesity: Why Do a Billion of Us Weigh 3 kg More?
AB  - Few would dispute that the current obesity epidemic has been driven by lifestyle
      and environmental changes. However, it is clear that individuals respond
      differently to these "obesigenic" changes and this variation in response has a
      strong genetic element. Genome-wide association studies have revealed that single
      nucleotide polymorphisms in Fat mass and obesity-associated transcript (FTO) are
      robustly associated with body mass index and obesity. Although the effect of
      these risk alleles are modest, with heterozygous and homozygous carriers weighing
      approximately 1.5 and 3 kg more respectively, there are an estimated one billion
      homozygous carriers in the world, spanning multiple different ethnicities and
      populations. Yet despite its broad impact, the biological function of FTO,
      particularly its role in controlling energy balance, remains unknown. Although
      the study of severe Mendelian obesity has been invaluable in illuminating
      critical pathways controlling food intake, the major burden of disease is carried
      by those of us with "common obesity," which to date has resisted yielding
      meaningful biological insights. FTO has at last given us a handle on a huge,
      worldwide, common problem. In this review, we focus on the available genetic and
      in vivo evidence to date that implicates FTO in the control of energy balance.

PMID- 22649361
TI  - Gender-Specific Adverse Effects of Mono-Ethylhexyl Phthalate on Steroidogenesis
      in Immature Granulosa Cells and Rat Leydig cell Progenitors in vitro.
AB  - Di-(2-ethylhexyl) phthalate, one of the phthalates most widely distributed in the
      environment, causes reproductive toxicity that is attributable to the action of
      its primary metabolite, mono-(2-ethylhexyl) phthalate (MEHP). Here, we have
      investigated the effects of MEHP on steroidogenesis by primary cultures of rat
      Leydig cell progenitors and immature granulosa cells. This phthalate stimulated
      basal steroidogenesis and steroidogenic acute regulatory protein (StAR)
      expression in both types of steroidogenic cells. However, when MEHP was incubated
      with (Bu)(2)cAMP, steroid production was increased in granulosa cells and
      suppressed in Leydig cell progenitors, a process associated with up-regulation of
      StAR expression. Our data suggest that MEHP exerts gender-specific adverse
      effects on the hormonal function of the developing gonads. This may be involved
      in the development of pathological conditions including disorders of prenatal sex
      development that may attenuate future reproductive health.

PMID- 22649362
TI  - The future of genomic endocrinology.

PMID- 22649363
TI  - An immunohistochemical method to study breast cancer cell subpopulations and
      their growth regulation by hormones in three-dimensional cultures.
AB  - The development of in vitro three-dimensional cell culture matrices offers
      physiologically relevant alternatives to traditional culture on plastic surfaces.
      However methods to analyze cell subpopulations therein are poor. Here we present
      a simple and inexpensive method to analyze cell subpopulations in mixed-cell
      colonies using standard immunohistochemical (IHC) techniques. Briefly, MatrigelTM
      blocks are sandwiched between two layers of HistoGelTM, hardened by rapid cooling
      then processed for routine fixation, paraffin embedding, and IHC. We demonstrate
      the assay using mono- and co-cultured normal human breast, human breast cancer,
      and transformed mouse stromal cells along with hormone treated breast cancer
      cells. Judicious selection of specific antibodies allows different cell types
      within heterotypic colonies to be identified. A brief pulse of bromodeoxyuridine
      in living colonies allows proliferation of cell subpopulations to be quantified.
      This simple assay is useful for multiple cell types, species, and conditions.

PMID- 22649364
TI  - Gonadotropin-releasing hormone and adipokinetic hormone signaling systems share a
      common evolutionary origin.
AB  - Gonadotropin-releasing hormone (GnRH) is a critical and central hormone that
      regulates vertebrate reproduction. The high conservation of GnRH signaling within
      the chordates (deuterostomians) raises the important question as to whether its
      appearance might date back prior to the divergence of protostomian and
      deuterostomian lineages, about 700 million years ago. This leads to several
      important questions regarding the evolution of the GnRH family. Has GnRH been
      retained in most protostomian lineages? And was regulation of reproduction
      already a function of ancestral GnRH? The first question can undoubtedly be
      answered affirmatively since several GnRH-like sequences have been found in wide
      variety of protostomian and deuterostomian phyla. However, based on their
      different primary functions in different phyla - which implies a less unanimous
      answer on the second question - consistency in the nomenclature of this peptide
      family has been lost. A comparative and phylogenetic approach shows that the
      ecdysozoan adipokinetic hormones (AKHs), lophotrochozoan GnRHs and chordate GnRHs
      are structurally related and suggests that they all originate from a common
      ancestor. This review supports the view that the AKH-GnRH signaling system
      probably arose very early in metazoan evolution, prior to the divergence of
      protostomians and deuterostomians.

PMID- 22649367
TI  - Diabetes and cancer.

PMID- 22649365
TI  - Angiotensin II, a Neuropeptide at the Frontier between Endocrinology and
      Neuroscience: Is There a Link between the Angiotensin II Type 2 Receptor and
      Alzheimer's Disease?
AB  - Amyloid-beta peptide deposition, abnormal hyperphosphorylation of tau, as well as
      inflammation and vascular damage, are associated with the development of
      Alzheimer's disease (AD). Angiotensin II (Ang II) is a peripheral hormone, as
      well as a neuropeptide, which binds two major receptors, namely the Ang II type 1
      receptor (AT1R) and the type 2 receptor (AT2R). Activation of the AT2R
      counteracts most of the AT1R-mediated actions, promoting vasodilation, decreasing
      the expression of pro-inflammatory cytokines, both in the brain and in the
      cardiovascular system. There is evidence that treatment with AT1R blockers (ARBs)
      attenuates learning and memory deficits. Studies suggest that the therapeutic
      effects of ARBs may reflect this unopposed activation of the AT2R in addition to
      the inhibition of the AT1R. Within the context of AD, modulation of AT2R
      signaling could improve cognitive performance not only through its action on
      blood flow/brain microcirculation but also through more specific effects on
      neurons. This review summarizes the current state of knowledge and potential
      therapeutic relevance of central actions of this enigmatic receptor. In
      particular, we highlight the possibility that selective AT2R activation by non
      peptide and highly selective agonists, acting on neuronal plasticity, could
      represent new pharmacological tools that may help improve impaired cognitive
      performance in AD and other neurological cognitive disorders.

PMID- 22649368
TI  - Hypopituitarism following traumatic brain injury: determining factors for
      diagnosis.
AB  - Neuroendocrine dysfunction, long recognized as a consequence of traumatic brain
      injury (TBI), is a major cause of disability that includes physical and
      psychological involvement with long-term cognitive, behavioral, and social
      changes. There is no standard procedure regarding at what time after trauma the
      diagnosis should be made. Also there is uncertainty on defining the best methods
      for diagnosis and testing and what types of patients should be selected for
      screening. Common criteria for evaluating these patients are required on account
      of the high prevalence of TBI worldwide and the potential new cases of
      hypopituitarism. The aim of this review is to clarify, based on the evidence,
      when endocrine assessment should be performed after TBI and which patients should
      be evaluated. Additional studies are still needed to know the impact of post
      traumatic hypopituitarism and to assess the impact of hormone replacement in the
      prognosis.

PMID- 22649366
TI  - Beyond the HPA Axis: Progesterone-Derived Neuroactive Steroids in Human Stress
      and Emotion.
AB  - Stress and social isolation are well-known risk factors for psychopathology.
      However, more research is needed as to the physiological mechanisms by which
      social support buffers the impacts of stress. Research in animal models suggests
      important roles for progesterone (P) and its product, the neuroactive steroid
      allopregnanolone (ALLO), in stress and psychopathology. These hormones are
      produced in brain and periphery during stress in rodents, and down-regulate
      anxiety behavior and hypothalamic-pituitary-adrenal axis activity. Human clinical
      populations, including depressed patients, have alterations in ALLO levels, but
      it is unclear whether these basal hormone level differences have clinical import.
      To begin to address this question, this review examines the role of P and ALLO in
      stress physiology, and the impact of these hormones on mood, in healthy humans.
      Evidence largely supports that P and ALLO increase during stress in humans.
      However, P/ALLO administration appears to cause only mild effects on mood and
      subjective anxiety, while exerting effects consistent with gamma-aminobutyric
      acid receptor modulation. Additionally, P is linked to motivation for
      affiliation/social contact; P (and ALLO) release may be especially responsive to
      social rejection. These observations lead to the novel hypothesis that stress
      related P/ALLO production functions not only to down-regulate stress and anxiety,
      but also to promote social contact as a long-term coping strategy. Malfunctioning
      of the P/ALLO system could therefore underlie depression partly by decreasing
      propensity to affiliate with others.

PMID- 22649370
TI  - Investigation of prolactin receptor activation and blockade using time-resolved
      fluorescence resonance energy transfer.
AB  - The prolactin receptor (PRLR) is emerging as a therapeutic target in oncology.
      Knowledge-based drug design led to the development of a pure PRLR antagonist
      (Del1-9-G129R-hPRL) that was recently shown to prevent PRL-induced mouse prostate
      tumorogenesis. In humans, the first gain-of-function mutation of the PRLR
      (PRLR(I146L)) was recently identified in breast tumor patients. At the molecular
      level, the actual mechanism of action of these two novel players in the PRL
      system remains elusive. In this study, we addressed whether constitutive PRLR
      activation (PRLR(I146L)) or PRLR blockade (antagonist) involved alteration of
      receptor oligomerization and/or of inter-chain distances compared to unstimulated
      and PRL-stimulated PRLR. Using a combination of various biochemical and
      spectroscopic approaches (co-IP, blue native electrophoresis, BRET(1)), we
      demonstrated that preformed PRLR homodimers are altered neither by PRL- or I146L
      induced receptor triggering, nor by antagonist-mediated blockade. These findings
      were confirmed using a novel time-resolved fluorescence resonance energy transfer
      (TR-FRET) technology that allows monitoring distance changes between cell surface
      tagged receptors. This technology revealed that PRLR blockade or activation did
      not involve detectable distance changes between extracellular domains of receptor
      chains within the dimer. This study merges with our previous structural
      investigations suggesting that the mechanism of PRLR activation solely involves
      intermolecular contact adaptations leading to subtle intramolecular
      rearrangements.

PMID- 22649369
TI  - Membrane-initiated estradiol signaling regulating sexual receptivity.
AB  - Estradiol has profound actions on the structure and function of the nervous
      system. In addition to nuclear actions that directly modulate gene expression,
      the idea that estradiol can rapidly activate cell signaling by binding to
      membrane estrogen receptors (mERs) has emerged. Even the regulation of sexual
      receptivity, an action previously thought to be completely regulated by nuclear
      ERs, has been shown to have a membrane-initiated estradiol signaling (MIES)
      component. This highlighted the question of the nature of mERs. Several
      candidates have been proposed, ERalpha, ERbeta, ER-X, GPR30 (G protein coupled
      estrogen receptor), and a receptor activated by a diphenylacrylamide compound,
      STX. Although each of these receptors has been shown to be active in specific
      assays, we present evidence for and against their participation in sexual
      receptivity by acting in the lordosis-regulating circuit. The initial MIES that
      activates the circuit is in the arcuate nucleus of the hypothalamus (ARH). Using
      both activation of MU-opioid receptors (MOR) in the medial preoptic nucleus and
      lordosis behavior, we document that both ERalpha and the STX-receptor participate
      in the required MIES. ERalpha and the STX-receptor activation of cell signaling
      are dependent on the transactivation of type 1 metabotropic glutamate receptors
      (mGluR1a) that augment progesterone synthesis in astrocytes and protein kinase C
      (PKC) in ARH neurons. While estradiol-induced sexual receptivity does not depend
      on neuroprogesterone, proceptive behaviors do. Moreover, the ERalpha and the STX
      receptor activation of medial preoptic MORs and augmentation of lordosis were
      sensitive to mGluR1a blockade. These observations suggest a common mechanism
      through which mERs are coupled to intracellular signaling cascades, not just in
      regulating reproduction, but in actions throughout the neuraxis including the
      cortex, hippocampus, striatum, and dorsal root ganglias.

PMID- 22649371
TI  - ERK, Akt, and STAT5 are Differentially Activated by the Two Growth Hormone
      Receptor Subtypes of a Teleost Fish (Oncorhynchus Mykiss).
AB  - Previously, we found that the teleost fish, rainbow trout, possesses two growth
      hormone receptor (GHR) subtypes that display distinct ligand-binding and agonist
      induced regulation features. In this study, we used Chinese hamster ovary-K1
      cells stably transfected individually with the two trout GHR subtypes, GHR1 and
      GHR2, to elucidate receptor-effector pathway linkages. Growth hormone (GH)
      stimulated rapid (5-10 min) phosphorylation of ERK, Akt, JAk2, and STAT5 in both
      GHR1- and GHR2-expressing cells; however; STAT5 was activated to a greater extent
      through GHR1 than through GHR2, whereas ERK and Akt were activated to a greater
      through GHR2 than through GHR1. Although blockade of the ERK pathway had no
      effect on the activation of Akt, inhibition of PI3K-Akt partially prevented
      activation of ERK, suggesting cross-talk between the ERK and PI3K-Akt pathways.
      JAK2 inhibition completely blocked activation of ERK, Akt, and STAT5, suggesting
      that all of these pathways link to GHR1 and GHR2 via JAK2. These findings
      establish important receptor-effector pathway linkages and suggest that the GHR
      subtypes of teleost fish may be functionally distinct.

PMID- 22649372
TI  - Developments in the imaging of brown adipose tissue and its associations with
      muscle, puberty, and health in children.
AB  - Fusion positron emission and computed tomography (PET/CT) remains the gold
      standard imaging modality to non-invasively study metabolically active brown
      adipose tissue (BAT). It has been widely applied to studies in adult cohorts. In
      contrast, the number of BAT studies in children has been few. This is largely
      limited by the elevated risk of ionizing radiation and radionuclide tracer usage
      by PET/CT and the ethical restriction of performing such exams on healthy
      children. However, metabolically active BAT has a significantly higher prevalence
      in pediatric patients, according to recent literature. Young cohorts thus
      represent an ideal population to examine the potential relationships of BAT to
      muscle development, puberty, disease state, and the accumulation of white adipose
      tissue. In turn, magnetic resonance imaging (MRI) represents the most promising
      modality to overcome the limitations of PET/CT. The development of rapid,
      repeatable MRI techniques to identify and quantify both metabolically active and
      inactive BAT non-invasively and without the use of exogenous contrast agents or
      the need for sedation in pediatric patients are critically needed to advance our
      knowledge of this tissue's physiology.

PMID- 22649373
TI  - Approach to lipid screening as a risk marker for cardiovascular disease in
      pediatric patients with diabetes.
AB  - Cardiovascular disease (CVD) is a well-known complication of diabetes mellitus
      (DM), and patients with DM are at an increased risk for early onset of CVD.
      Hyperglycemia is believed to be the primary mediator in premature development of
      atherosclerosis in patients with DM, but there are also derangements in
      cholesterol levels and inflammatory markers beyond the explanation of
      hyperglycemia. Although clinicians often screen for dyslipidemia as part of
      routine care for children and adolescents with DM, many do not feel comfortable
      treating this condition. Multiple guidelines exist to help clinicians with the
      prevention, screening, and treatment of CVD risk factors in pediatric patients
      with DM, but the guidelines do not always agree on screening intervals or medical
      treatment. Furthermore, the cost-effectiveness of medication use in this
      population has not been established. Research has advanced our understanding of
      the role of other biomarkers and radiologic studies of CVD risk, but these
      studies do not currently have a place in routine clinical practice. It is evident
      that the increased CVD risk in pediatric patients with DM is complex in origin
      and the optimal approach to managing dyslipidemia remains unclear. Therefore, an
      algorithm designed at the University of North Carolina (UNC), Division of
      Pediatric Endocrinology, is presented to help guide clinicians through screening
      and treatment of dyslipidemia in youth with DM.

PMID- 22649374
TI  - Conformational dynamics of insulin.
AB  - We have exploited a prandial insulin analog to elucidate the underlying structure
      and dynamics of insulin as a monomer in solution. A model was provided by insulin
      lispro (the active component of Humalog((r)); Eli Lilly and Co.). Whereas NMR
      based modeling recapitulated structural relationships of insulin crystals (T
      state protomers), dynamic anomalies were revealed by amide-proton exchange
      kinetics in D(2)O. Surprisingly, the majority of hydrogen bonds observed in
      crystal structures are only transiently maintained in solution, including key T
      state-specific inter-chain contacts. Long-lived hydrogen bonds (as defined by
      global exchange kinetics) exist only at a subset of four alpha-helical sites (two
      per chain) flanking an internal disulfide bridge (cystine A20-B19); these sites
      map within the proposed folding nucleus of proinsulin. The anomalous flexibility
      of insulin otherwise spans its active surface and may facilitate receptor
      binding. Because conformational fluctuations promote the degradation of
      pharmaceutical formulations, we envisage that "dynamic re-engineering" of insulin
      may enable design of ultra-stable formulations for humanitarian use in the
      developing world.

PMID- 22649376
TI  - Insulin signaling and autism.

PMID- 22649375
TI  - Neuroprotective actions of neurosteroids.
AB  - Neurosteroids were initially defined as steroid hormones locally synthesized
      within the nervous tissue. Subsequently, they were described as steroid hormone
      derivatives that devoid hormonal action but still affect neuronal excitability
      through modulation of ionotropic receptors. Neurosteroids are further subdivided
      into natural (produced in the brain) and synthetic. Some authors distinguish
      between hormonal and regular neurosteroids in the group of natural ones. The
      latter group, including hormone metabolites like allopregnanolone or
      tetrahydrodeoxycorticosterone, is devoid of hormonal activity. Both hormones and
      their derivatives share, however, most of the physiological functions. It is
      usually very difficult to distinguish the effects of hormones and their
      metabolites. All these substances may influence seizure phenomena and exhibit
      neuroprotective effects. Neuroprotection offered by steroid hormones may be
      realized in both genomic and non-genomic mechanisms and involve regulation of the
      pro- and anti-apoptotic factors expression, intracellular signaling pathways,
      neurotransmission, oxidative, and inflammatory processes. Since regular
      neurosteroids show no affinity for steroid receptors, they may act only in a non
      genomic mode. Multiple studies have been conducted so far to show efficacy of
      neurosteroids in the treatment of the central and peripheral nervous system
      injury, ischemia, neurodegenerative diseases, or seizures. In this review we
      focused primarily on neurosteroid mechanisms of action and their role in the
      process of neurodegeneration. Most of the data refers to results obtained in
      experimental studies. However, it should be realized that knowledge about
      neuroactive steroids remains still incomplete and requires confirmation in
      clinical conditions.

PMID- 22649377
TI  - Enhanced Sensitivity to Ethanol-Induced Inhibition of LTP in CA1 Pyramidal
      Neurons of Socially Isolated C57BL/6J Mice: Role of Neurosteroids.
AB  - Ethanol (EtOH) induced impairment of long-term potentiation (LTP) in the rat
      hippocampus is prevented by the 5alpha-reductase inhibitor finasteride,
      suggesting that this effect of EtOH is dependent on the increased local release
      of neurosteroids such as 3alpha,5alpha-THP that promote GABA-mediated
      transmission. Given that social isolation (SI) in rodents is associated with
      altered plasma and brain levels of such neurosteroids as well as with an enhanced
      neurosteroidogenic action of EtOH, we examined whether the inhibitory effect of
      EtOH on LTP at CA3-CA1 hippocampal excitatory synapses is altered in C57BL/6J
      mice subjected to SI for 6 weeks in comparison with group-housed (GH) animals.
      Extracellular recording of field excitatory postsynaptic potentials (fEPSPs) as
      well as patch-clamp analysis were performed in hippocampal slices prepared from
      both SI and GH mice. Consistent with previous observations, recording of fEPSPs
      revealed that the extent of LTP induced in the CA1 region of SI mice was
      significantly reduced compared with that in GH animals. EtOH (40 mM) inhibited
      LTP in slices from SI mice but not in those from GH mice, and this effect of EtOH
      was abolished by co-application of 1 MUM finasteride. Current-clamp analysis of
      CA1 pyramidal neurons revealed a decrease in action potential (AP) frequency and
      an increase in the intensity of injected current required to evoke the first AP
      in SI mice compared with GH mice, indicative of a decrease in neuronal
      excitability associated with SI. Together, our data suggest that SI results in
      reduced levels of neuronal excitability and synaptic plasticity in the
      hippocampus. Furthermore, the increased sensitivity to the neurosteroidogenic
      effect of EtOH associated with SI likely accounts for the greater inhibitory
      effect of EtOH on LTP in SI mice. The increase in EtOH sensitivity induced by SI
      may be important for the changes in the effects of EtOH on anxiety and on
      learning and memory associated with the prolonged stress attributable to SI.

PMID- 22649378
TI  - The ventral premammillary nucleus links metabolic cues and reproduction.
AB  - The amount of body fat and the energy balance are important factors that
      influence the timing of puberty and the normal reproductive function. Leptin is a
      key hormone that conveys to the central nervous system information about the
      individual energy reserve and modulates the hypothalamus-pituitary-gonad (HPG)
      axis. Recent findings suggest that the ventral premammillary nucleus (PMV)
      mediates the effects of leptin as a permissive factor for the onset of puberty
      and the coordinated secretion of luteinizing hormone during conditions of
      negative energy balance. In this review, we will summarize the existing
      literature about the potential role played by PMV neurons in the regulation of
      the HPG axis.

PMID- 22649380
TI  - A role for the androgen metabolite, 5alpha androstane 3beta, 17beta diol (3beta
      diol) in the regulation of the hypothalamo-pituitary-adrenal axis.
AB  - Activation of the hypothalamo-pituitary-adrenal (HPA) axis is a basic reaction of
      animals to environmental perturbations that threaten homeostasis. These responses
      are ultimately regulated by neurons residing within the paraventricular nucleus
      (PVN) of the hypothalamus. Within the PVN, corticotrophin-releasing hormone
      (CRH), vasopressin (AVP), and oxytocin (OT) expressing neurons are critical as
      they can regulate both neuroendocrine and autonomic responses. Estradiol (E2) and
      testosterone (T) are well known reproductive hormones; however, they have also
      been shown to modulate stress reactivity. In rodent models, evidence shows that
      under some conditions E2 enhances stress activated adrenocorticotropic hormone
      (ACTH) and corticosterone secretion. In contrast, T decreases the gain of the HPA
      axis. The modulatory role of testosterone was originally thought to be via 5
      alpha reduction to the potent androgen dihydrotestosterone (DHT) and its
      subsequent binding to the androgen receptor, whereas E2 effects were thought to
      be mediated by estrogen receptors alpha (ERalpha) and beta (ERbeta). However, DHT
      has been shown to be metabolized to the ERbeta agonist, 5alpha- androstane 3beta,
      17beta Diol (3beta-Diol). The actions of 3beta-Diol on the HPA axis are mediated
      by ERbeta which inhibits the PVN response to stressors. In gonadectomized rats,
      ERbeta agonists reduce CORT and ACTH responses to restraint stress, an effect
      that is also present in wild-type but not ERbeta-knockout mice. The
      neurobiological mechanisms underlying the ability of ERbeta to alter HPA
      reactivity are not currently known. CRH, AVP, and OT have all been shown to be
      regulated by estradiol and recent studies indicate an important role of ERbeta in
      these regulatory processes. Moreover, activation of the CRH and AVP promoters has
      been shown to occur by 3beta-Diol binding to ERbeta and this is thought to occur
      through alternate pathways of gene regulation. Based on available data, a novel
      and important role of 3beta-Diol in the regulation of the HPA axis is suggested.

PMID- 22649381
TI  - Ghrelin Receptor Deficiency does not Affect Diet-Induced Atherosclerosis in Low
      Density Lipoprotein Receptor-Null Mice.
AB  - OBJECTIVE: Ghrelin, a stomach-derived, secreted peptide, and its receptor (growth
      hormone secretagogue receptor, GHSR) are known to modulate food intake and energy
      homeostasis. The ghrelin system is also expressed broadly in cardiovascular
      tissues. Since ghrelin has been associated with anti-inflammatory and anti
      atherogenic properties, but is also well known to promote obesity and impair
      glucose metabolism, we investigated whether ghrelin has any impact on the
      development of atherosclerosis. The hypothesis that endogenous ghrelin signaling
      may be involved in atherosclerosis has not been tested previously. METHODS AND
      RESULTS: We crossed ghrelin receptor knockout mice (GHSr(-/-)) into a low-density
      lipoprotein receptor-null (Ldlr(-/-)) mouse line. In this model, atherosclerotic
      lesions were promoted by feeding a high-fat, high-cholesterol Western-type diet
      for 13 months, following a standard protocol. Body composition and glucose
      homeostasis were similar between Ldlr(-/-) and Ldlr/GHSR(-/-)ko mice throughout
      the study. Absence or presence of GHSr did not alter the apolipoprotein profile
      changes in response to diet exposure on an LDLRko background. Atherosclerotic
      plaque volume in the aortic arch and thoracic aorta were also not affected
      differentially in mice without ghrelin signaling due to GHSR gene disruption as
      compared to control LDLRko littermates. In light of the associations reported for
      ghrelin with cardiovascular disease in humans, the lack of a phenotype in these
      loss-of-function studies in mice suggests no direct role for endogenous ghrelin
      in either the inhibition or the promotion of diet-induced atherosclerosis.
      CONCLUSION: These data indicate that, surprisingly, the complex and multifaceted
      actions of endogenous ghrelin receptor mediated signaling on the cardiovascular
      system have minimal direct impact on atherosclerotic plaque progression as based
      on a loss-of-function mouse model of the disease.

PMID- 22649379
TI  - Adiponectin action: a combination of endocrine and autocrine/paracrine effects.
AB  - The widespread physiological actions of adiponectin have now been well
      characterized as clinical studies and works in animal models have established
      strong correlations between circulating adiponectin level and various disease
      related outcomes. Thus, conventional thinking attributes many of adiponectin's
      beneficial effects to endocrine actions of adipose-derived adiponectin. However,
      it is now clear that several tissues can themselves produce adiponectin and there
      is growing evidence that locally produced adiponectin can mediate functionally
      important autocrine or paracrine effects. In this review article we discuss
      regulation of adiponectin production, its mechanism of action via receptor
      isoforms and signaling pathways, and its principal physiological effects (i.e.,
      metabolic and cardiovascular). The role of endocrine actions of adiponectin and
      changes in local production of adiponectin or its receptors in whole body
      physiology is discussed.

PMID- 22649382
TI  - Extracellular domain N-glycosylation controls human thrombopoietin receptor cell
      surface levels.
AB  - The thrombopoietin receptor (TpoR) is a type I transmembrane protein that
      mediates the signaling functions of thrombopoietin (Tpo) in regulating
      megakaryocyte differentiation, platelet formation, and hematopoietic stem cell
      renewal. We probed the role of each of the four extracellular domain putative N
      glycosylation sites for cell surface localization and function of the receptor.
      Single N-glycosylation mutants at any of the four sites were able to acquire the
      mature N-glycosylated pattern, but exhibited a decreased Tpo-dependent JAK2-STAT
      response in stably transduced Ba/F3 or Ba/F3-JAK2 cell lines. The ability of JAK2
      to promote cell surface localization and stability of TpoR required the first N
      glycosylation site (Asn117). In contrast, the third N-glycosylation site (Asn298)
      decreased receptor maturation and stability. TpoR mutants lacking three N
      glycosylation sites were defective in maturation, but N-glycosylation on the
      single remaining site could be detected by sensitivity to PNGaseF. The TpoR
      mutant defective in all four N-glycosylation sites was severely impaired in
      plasma membrane localization and was degraded by the proteasome. N-glycosylation
      receptor mutants are not misfolded as, once localized on the cell surface in
      overexpression conditions, they can bind and respond to Tpo. Our data indicate
      that extracellular domain N-glycosylation sites regulate in a combinatorial
      manner cell surface localization of TpoR. We discuss how mutations around TpoR N
      glycosylation sites might contribute to inefficient receptor traffic and disease.

PMID- 22649385
TI  - Biosynthetic Pathway for Sex Pheromone Components Produced in a Plusiinae Moth,
      Plusia festucae.
AB  - While many Plusiinae species commonly secrete (Z)-7-dodecenyl acetate (Z7-12:OAc)
      as a key pheromone component, female moths of the rice looper (Plusia festucae)
      exceptionally utilize (Z)-5-dodecenyl acetate (Z5-12:OAc) to communicate with
      their partners. GC-MS analysis of methyl esters derived from fatty acids included
      in the pheromone gland of P. festucae showed a series of esters monounsaturated
      at the omega7-position, i.e., (Z)-5-dodecenoate, (Z)-7-tetradecenoate, (Z)-9
      hexadecenoate (Z9-16:Me), and (Z)-11-octadecenoate (Z11-18:Me). By topical
      application of D(3)-labled palmitic acid (16:Acid) and stearic acid (18:Acid) to
      the pheromone glands, similar amounts of D(3)-Z5-12:OAc were detected. The glands
      treated with D(13)-labeled monoenoic acids (Z9-16:Acid and Z11-18:Acid), which
      were custom-made by utilizing an acetylene coupling reaction with D(13)-1
      bromohexane, also produced similar amounts of D(13)-Z5-12:OAc. These results
      suggested that Z5-12:OAc was biosynthesized by omega7-desaturase with low
      substrate specificity, which could introduce a double bond at the 9-position of a
      16:Acid derivative and the 11-position of an 18:Acid derivative. Additional
      experiments with the glands pretreated with an inhibitor of chain elongation
      supported this speculation. Furthermore, a comparative study with another
      Plusiinae species (Chrysodeixis eriosoma) secreting Z7-12:OAc indicated that the
      beta-oxidation systems of P. festucae and C. eriosoma were different.

PMID- 22649383
TI  - Steroidogenic acute regulatory protein expression in the central nervous system.
AB  - Locally produced neurosteroids are proposed to have many functions in the central
      nervous system. The identification of the steroidogenic acute regulatory protein
      in steroid-producing neural cells provides a new tool to understand the sites,
      regulation, and importance of their synthesis.

PMID- 22649386
TI  - Effects of methylphenidate on weight gain and food intake in hypothalamic
      obesity.
AB  - For patients with a craniopharyngioma (CP), treatment of hypothalamic obesity
      (HO) and hyperphagia following resection and/or radiotherapy is extremely
      difficult and few reports have been published on potential drug therapies.
      Psychomotor stimulant methylphenidate (MPH) has been reported to inhibit food
      intake (FI). In this paper, we report reduction of body mass index (BMI) and
      appetite in an adolescent CP patient suffering from HO. We then tested the
      ability of MPH to attenuate the FI and body weight (BW) gain in a rat model
      consistent with the neuroanatomical and metabolic disturbances commonly observed
      in obese CP patients. Specifically, we used a novel electrolytically generated
      combined medial hypothalamic lesion (CMHL) affecting the arcuate nucleus,
      ventromedial hypothalamic nucleus, and dorsomedial hypothalamic nucleus to induce
      hyperphagia, rapid weight gain, and adiposity. Both CMHL and control animals (n =
      7 per group) were administered either methylphenidate HCl (MPH; 20 mg kg(-1) day(
      1)) or saline for 4 days in a crossover design experiment 28 weeks post-surgery.
      A significant decrease in percent baseline FI (CMHL -23%, p = 0.008; control 
      20%, p = 0.002) and percent change in BW (CMHL -1.97%/4 days, p = 0.011; control 
      1.75%/4 days, p = 0.003) was observed during MPH treatment as compared to saline.
      CONCLUSION: This study shows MPH treatment of severely obese CMHL rats resulted
      in significantly reduced FI and BW loss.

PMID- 22649384
TI  - Neurosteroids reduce social isolation-induced behavioral deficits: a proposed
      link with neurosteroid-mediated upregulation of BDNF expression.
AB  - The pharmacological action of selective serotonin reuptake inhibitor
      antidepressants may include a normalization of the decreased brain levels of the
      brain-derived neurotrophic factor (BDNF) and of neurosteroids such as the
      progesterone metabolite allopregnanolone, which are decreased in patients with
      depression and posttraumatic stress disorders (PTSD). The allopregnanolone and
      BDNF level decrease in PTSD and depressed patients is associated with behavioral
      symptom severity. Antidepressant treatment upregulates both allopregnanolone
      levels and the expression of BDNF in a manner that significantly correlates with
      improved symptomatology, which suggests that neurosteroid biosynthesis and BDNF
      expression may be interrelated. Preclinical studies using the socially isolated
      mouse as an animal model of behavioral deficits, which resemble some of the
      symptoms observed in PTSD patients, have shown that fluoxetine and derivatives
      improve anxiety-like behavior, fear responses and aggressive behavior by
      elevating the corticolimbic levels of allopregnanolone and BDNF mRNA expression.
      These actions appeared to be independent and more selective than the action of
      these drugs on serotonin reuptake inhibition. Hence, this review addresses the
      hypothesis that in PTSD or depressed patients, brain allopregnanolone levels, and
      BDNF expression upregulation may be mechanisms at least partially involved in the
      beneficial actions of antidepressants or other selective brain steroidogenic
      stimulant molecules.

PMID- 22649387
TI  - Neurosteroid biosynthesis in the brain of amphibians.
AB  - Amphibians have been widely used to investigate the synthesis of biologically
      active steroids in the brain and the regulation of neurosteroid production by
      neurotransmitters and neuropeptides. The aim of the present review is to
      summarize the current knowledge regarding the neuroanatomical distribution and
      biochemical activity of steroidogenic enzymes in the brain of anurans and
      urodeles. The data accumulated over the past two decades demonstrate that
      discrete populations of neurons and/or glial cells in the frog and newt brains
      express the major steroidogenic enzymes and are able to synthesize de novo a
      number of neurosteroids from cholesterol/pregnenolone. Since neurosteroidogenesis
      has been conserved during evolution from amphibians to mammals, it appears that
      neurosteroids must play important physiological functions in the central nervous
      system of vertebrates.

PMID- 22649389
TI  - Uncoupling protein 1 of brown adipocytes, the only uncoupler: a historical
      perspective.
AB  - Uncoupling protein 1 (UCP1), is a unique mitochondrial membranous protein devoted
      to adaptive thermogenesis, a specialized function performed by brown adipocytes.
      Whereas the family of mitochondrial metabolite carriers comprises ~40 members,
      UCP1 is the only memberable to translocate protons through the inner membrane of
      brown adipocyte mitochondria. By this process, UCP1 uncouples respiration from
      ATP synthesis and therefore provokes energy dissipation in the form of heat
      while, also stimulating high levels of fatty acid oxidation. UCP1 homologs were
      identified but they are biochemically and physiologically different from UCP1.
      Thirty five years after its identification, UCP1 still appears as a fascinating
      component. The recent renewal of the interest in human brown adipose tissue makes
      UCP1 as a potential target for strategies of treatment of metabolic disorders.

PMID- 22649388
TI  - Peripheral vs. Central Sex Steroid Hormones in Experimental Parkinson's Disease.
AB  - The nigrostriatal dopaminergic (NSDA) pathway degenerates in Parkinson's disease
      (PD), which occurs with approximately twice the incidence in men than women.
      Studies of the influence of systemic estrogens in females suggest sex hormones
      contribute to these differences. In this review we analyze the evidence revealing
      great complexity in the response of the healthy and injured NSDA system to
      hormonal influences, and emphasize the importance of centrally generated
      estrogens. At physiological levels, circulating estrogen (in females) or estrogen
      precursors (testosterone in males, aromatized to estrogen centrally) have
      negligible effects on dopaminergic neuron survival in experimental PD, but can
      modify striatal dopamine levels via actions on the activity or adaptive responses
      of surviving cells. However, these effects are sexually dimorphic. In females,
      estradiol promotes adaptive responses in the partially injured NSDA pathway,
      preserving striatal dopamine, whereas in males gonadal steroids and exogenous
      estradiol have a negligible or even suppressive effect, effectively exacerbating
      dopamine loss. On balance, the different effects of gonadal factors in males and
      females contribute to sex differences in experimental PD. Fundamental sex
      differences in brain organization, including the sexually dimorphic networks
      regulating NSDA activity are likely to underpin these responses. In contrast,
      estrogen generated locally appears to preserve striatal dopamine in both sexes.
      The available data therefore highlight the need to understand the biological
      basis of sex-specific responses of the NSDA system to peripheral hormones, so as
      to realize the potential for sex-specific, hormone-based therapies in PD.
      Furthermore, they suggest that targeting central steroid generation could be
      equally effective in preserving striatal dopamine in both sexes. Clarification of
      the relative roles of peripheral and central sex steroid hormones is thus an
      important challenge for future studies.

PMID- 22649390
TI  - Therapeutic prospects of metabolically active brown adipose tissue in humans.
AB  - The world-wide obesity epidemic constitutes a severe threat to human health and
      wellbeing and poses a major challenge to health-care systems. Current therapeutic
      approaches, relying mainly on reduced energy intake and/or increased exercise
      energy expenditure, are generally of limited effectiveness. Previously believed
      to be present only in children, the existence of metabolically active brown
      adipose tissue (BAT) was recently demonstrated also in healthy human adults. The
      physiological role of BAT is to dissipate chemical energy, mainly from fatty
      acids, as heat to maintain body temperature in cold environments. Recent studies
      indicate that the activity of BAT is negatively correlated with overweight and
      obesity, findings that raise the exciting possibility of new and effective weight
      reduction therapies based on increased BAT energy expenditure, a process likely
      to be amenable to pharmacological intervention.

PMID- 22649392
TI  - Screening for the Genes Involved in Bombykol Biosynthesis: Identification and
      Functional Characterization of Bombyx mori Acyl Carrier Protein.
AB  - Species-specific sex pheromones released by female moths to attract conspecific
      male moths are synthesized de novo in the pheromone gland (PG) via fatty acid
      synthesis (FAS). Biosynthesis of moth sex pheromones is usually regulated by a
      neurohormone termed pheromone biosynthesis activating neuropeptide (PBAN), a 33
      aa peptide that originates in the subesophageal ganglion. In the silkmoth, Bombyx
      mori, cytoplasmic lipid droplets (LDs), which store the sex pheromone (bombykol)
      precursor fatty acid, accumulate in PG cells prior to eclosion. PBAN activation
      of the PBAN receptor stimulates lipolysis of the stored LD triacylglycerols
      (TAGs) resulting in release of the bombykol precursor for final modification.
      While we have previously characterized a number of molecules involved in bombykol
      biosynthesis, little is known about the mechanisms of PBAN signaling that
      regulate the TAG lipolysis in PG cells. In the current study, we sought to
      further identify genes involved in bombykol biosynthesis as well as PBAN
      signaling, by using a subset of 312 expressed-sequence tag (EST) clones that are
      in either our B. mori PG cDNA library or the public B. mori EST databases,
      SilkBase and CYBERGATE, and which are preferentially expressed in the PG. Using
      RT-PCR expression analysis and an RNAi screening approach, we have identified
      another eight EST clones involved in bombykol biosynthesis. Furthermore, we have
      determined the functional role of a clone designated BmACP that encodes B. mori
      acyl carrier protein (ACP). Our results indicate that BmACP plays an essential
      role in the biosynthesis of the bombykol precursor fatty acid via the canonical
      FAS pathway during pheromonogenesis.

PMID- 22649391
TI  - Gliotransmission by prostaglandin e(2): a prerequisite for GnRH neuronal
      function?
AB  - Over the past four decades it has become clear that prostaglandin E(2) (PGE(2)),
      a phospholipid-derived signaling molecule, plays a fundamental role in modulating
      the gonadotropin-releasing hormone (GnRH) neuroendocrine system and in shaping
      the hypothalamus. In this review, after a brief historical overview, we highlight
      studies revealing that PGE(2) released by glial cells such as astrocytes and
      tanycytes is intimately involved in the active control of GnRH neuronal activity
      and neurosecretion. Recent evidence suggests that hypothalamic astrocytes
      surrounding GnRH neuronal cell bodies may respond to neuronal activity with an
      activation of the erbB receptor tyrosine kinase signaling, triggering the release
      of PGE(2) as a chemical transmitter from the glia themselves, and, in turn,
      leading to the feedback regulation of GnRH neuronal activity. At the GnRH
      neurohemal junction, in the median eminence of the hypothalamus, PGE(2) is
      released by tanycytes in response to cell-cell signaling initiated by glial cells
      and vascular endothelial cells. Upon its release, PGE(2) causes the retraction of
      the tanycyte end-feet enwrapping the GnRH nerve terminals, enabling them to
      approach the adjacent pericapillary space and thus likely facilitating
      neurohormone diffusion from these nerve terminals into the pituitary portal
      blood. In view of these new insights, we suggest that synaptically associated
      astrocytes and perijunctional tanycytes are integral modulatory elements of GnRH
      neuronal function at the cell soma/dendrite and nerve terminal levels,
      respectively.

PMID- 22649393
TI  - Computed tomography of subchondral bone and osteophytes in hip osteoarthritis:
      the shape of things to come?
AB  - Bone is a fundamental component of the disordered joint homeostasis seen in
      osteoarthritis, a disease that has been primarily characterized by the breakdown
      of articular cartilage accompanied by local bone changes and a limited degree of
      joint inflammation. In this review we consider the role of computed tomography
      imaging and computational analysis in osteoarthritis research, focusing on
      subchondral bone and osteophytes in the hip. We relate what is already known in
      this area to what could be explored through this approach in the future in
      relation to both clinical research trials and the underlying cellular and
      molecular science of osteoarthritis. We also consider how this area of research
      could impact on our understanding of the genetics of osteoarthritis.

PMID- 22649395
TI  - Association of Cigarette Smoking with Aberrant Methylation of the Tumor
      Suppressor Gene RARbeta2 in Papillary Thyroid Cancer.
AB  - Aberrant gene methylation is often seen in thyroid cancer, a common endocrine
      malignancy. Tobacco smoking has been shown to be associated with aberrant gene
      methylation in several cancers, but its relationship with gene methylation in
      thyroid cancer has not been examined. In the present study, we investigated the
      relationship between smoking of patients and aberrant methylation of tumor
      suppressor genes for TIMP3, SLC5A8, death-associated protein kinase, and retinoic
      acid receptor beta2 (RARbeta2) in papillary thyroid cancer (PTC), the most common
      type of thyroid cancer. The promoter methylation status of these genes was
      analyzed using quantitative real-time methylation-specific PCR on bisulfite
      treated genomic DNA isolated from tumor tissues and correlated with smoking
      history of the patients. Among the four genes, methylation of the RARbeta2 gene
      was significantly associated with smoking and other three genes showed a trend of
      association. Specifically, among the 138 patients investigated, 13/42 (31.0%)
      ever smokers vs. 10/96 (10.4%) never smokers harbored methylation of the RARbeta2
      gene (P = 0.003). This association was highly significant also in the subset of
      conventional variant PTC (P = 0.005) and marginally significant in follicular
      variant PTC (P = 0.06). The results demonstrate that smoking-associated aberrant
      methylation of the RARbeta2 gene is a specific molecular event that may represent
      an important mechanism in thyroid tumorigenesis in smokers.

PMID- 22649394
TI  - Cross-Talk between Metabolism and Reproduction: The Role of POMC and SF1 Neurons.
AB  - Energy homeostasis and reproduction require tight coordination, but the
      mechanisms underlying their interaction are not fully understood. Two sets of
      hypothalamic neurons, namely pro-opiomelanocortin (POMC) neurons in the arcuate
      nucleus and steroidogenic factor-1 (SF1) neurons in the ventromedial hypothalamic
      nucleus, are emerging as critical nodes where metabolic and reproductive signals
      communicate. This view is supported by recent genetic studies showing that
      disruption of metabolic signals (e.g., leptin and insulin) or reproductive
      signals (e.g., estradiol) in these neurons leads to impaired regulation of both
      energy homeostasis and fertility. In this review, we will examine the potential
      mechanisms of neuronal communication between POMC, SF1, and gonadotropin
      releasing hormone neurons in the regulation of metabolism and reproduction.

PMID- 22649397
TI  - Timing is Everything: PTTH Mediated DHR4 Nucleocytoplasmic Trafficking Sets the
      Tempo of Drosophila Steroid Production.
AB  - During development, multicellular organisms must become sexually mature in order
      to reproduce. The developmental timing of this transition is controlled by pulses
      of steroid hormones, but how these pulses are generated have remained unclear? A
      recent paper shows that in Drosophila larvae, nucleocytoplasmic trafficking of
      DHR4, a nuclear receptor, in response to prothoracicotropic hormone signaling, is
      critical for producing the correct temporal pulses of steroid hormones that
      coordinate the juvenile-adult transition.

PMID- 22649396
TI  - Food Restriction-Induced Changes in Gonadotropin-Inhibiting Hormone Cells are
      Associated with Changes in Sexual Motivation and Food Hoarding, but not Sexual
      Performance and Food Intake.
AB  - We hypothesized that putative anorectic and orexigenic peptides control the
      motivation to engage in either ingestive or sex behaviors, and these peptides
      function to optimize reproductive success in environments where energy
      fluctuates. Here, the putative orexigenic peptide, gonadotropin-inhibiting
      hormone (GnIH, also known as RFamide-related peptide-3), and the putative
      anorectic hormones leptin, insulin, and estradiol were examined during the course
      of food restriction. Groups of female Syrian hamsters were restricted to 75% of
      their ad libitum food intake or fed ad libitum for 4, 8, or 12 days. Two other
      groups were food-restricted for 12 days and then re-fed ad libitum for 4 or 8
      days. After testing for sex and ingestive behavior, blood was sampled and assayed
      for peripheral hormones. Brains were immunohistochemically double-labeled for
      GnIH and the protein product of the immediate early gene, c-fos, a marker of
      cellular activation. Food hoarding, the number of double-labeled cells, and the
      percent of GnIH-Ir cells labeled with Fos-Ir were significantly increased at 8
      and 12 days after the start of food restriction. Vaginal scent marking and GnIH
      Ir cell number significantly decreased after the same duration of restriction.
      Food hoarding, but not food intake, was significantly positively correlated with
      cellular activation in GnIH-Ir cells. Vaginal scent marking was significantly
      negatively correlated with cellular activation in GnIH-Ir cells. There were no
      significant effects of food restriction on plasma insulin, leptin, estradiol, or
      progesterone concentrations. In the dorsomedial hypothalamus (DMH) of
      energetically challenged females, strong projections from NPY-Ir cells were found
      in close apposition to GnIH-Ir cells. Together these results are consistent with
      the idea that metabolic signals influence sexual and ingestive motivation via NPY
      fibers that project to GnIH cells in the DMH.

PMID- 22649398
TI  - Transcriptome-wide identification of preferentially expressed genes in the
      hypothalamus and pituitary gland.
AB  - To identify preferentially expressed genes in the central endocrine organs of the
      hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles
      of the hypothalamus, pituitary gland, and parietal cortex in male mice (12-15
      weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE
      tags for the hypothalamus, pituitary gland, and parietal cortex were 165824,
      126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131
      distinct tags, respectively. Comparison of these mRNA profiles revealed that 22
      mRNA species, including three potential novel transcripts, were preferentially
      expressed in the hypothalamus. In addition to well-known hypothalamic
      transcripts, such as hypocretin, several genes involved in hormone function,
      intracellular transduction, metabolism, protein transport, steroidogenesis,
      extracellular matrix, and brain disease were identified as preferentially
      expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species,
      including 60 potential novel transcripts, were preferentially expressed. In
      addition to well-known pituitary genes, such as growth hormone and thyroid
      stimulating hormone beta, a number of genes classified to function in transport,
      amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond
      formation, stress response, transcription, protein synthesis, and turnover, cell
      differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix
      were also preferentially expressed. In conclusion, the current study identified
      not only well-known hypothalamic and pituitary transcripts but also a number of
      new candidates likely to be involved in endocrine homeostatic systems regulated
      by the hypothalamus and pituitary gland.

PMID- 22649399
TI  - Drug discovery opportunities and challenges at g protein coupled receptors for
      long chain free Fatty acids.
AB  - Discovery of G protein coupled receptors for long chain free fatty acids (FFAs),
      FFA1 (GPR40) and GPR120, has expanded our understanding of these nutrients as
      signaling molecules. These receptors have emerged as important sensors for FFA
      levels in the circulation or the gut lumen, based on evidence from in vitro and
      rodent models, and an increasing number of human studies. Here we consider their
      promise as therapeutic targets for metabolic disease, including type 2 diabetes
      and obesity. FFA1 directly mediates acute FFA-induced glucose-stimulated insulin
      secretion in pancreatic beta-cells, while GPR120 and FFA1 trigger release of
      incretins from intestinal endocrine cells, and so indirectly enhance insulin
      secretion and promote satiety. GPR120 signaling in adipocytes and macrophages
      also results in insulin sensitizing and beneficial anti-inflammatory effects.
      Drug discovery has focused on agonists to replicate acute benefits of FFA
      receptor signaling, with promising early results for FFA1 agonists in man.
      Controversy surrounding chronic effects of FFA1 on beta-cells illustrates that
      long term benefits of antagonists also need exploring. It has proved challenging
      to generate highly selective potent ligands for FFA1 or GPR120 subtypes, given
      that both receptors have hydrophobic orthosteric binding sites, which are not
      completely defined and have modest ligand affinity. Structure activity
      relationships are also reliant on functional read outs, in the absence of robust
      binding assays to provide direct affinity estimates. Nevertheless synthetic
      ligands have already helped dissect specific contributions of FFA1 and GPR120
      signaling from the many possible cellular effects of FFAs. Approaches including
      use of fluorescent ligand binding assays, and targeting allosteric receptor
      sites, may improve further pre-clinical ligand development at these receptors, to
      exploit their unique potential to target multiple facets of diabetes.

PMID- 22649400
TI  - Functional Characterization of Hypertrehalosemic Hormone Receptor in Relation to
      Hemolymph Trehalose and to Oxidative Stress in the Cockroach Blattella germanica.
AB  - Hypertrehalosemic hormone (HTH) is a peptide hormone that belongs to the
      adipokinetic hormone/red pigment concentrating hormone (AKH/RPCH) family, which
      exerts pleiotropic actions related to catabolic reaction and stress response. AKH
      peptides have been demonstrated to participate in stress response including
      oxidative stress in several insects. In order to study the signaling pathway of
      HTH involved in anti-oxidative stress, we have characterized a HIH receptor cDNA
      in Blattella germanica (Blage-HTHR) in structural and in functional terms using
      RNA interference (RNAi). Blage-HTHR is expressed in various female adult tissues
      (brain-CC-CA, ventral nerve cord, midgut, fat body, oviduct), but maximal
      expression is observed in the fat body. RNAi-mediated knockdown of Blage-HTHR
      expression results in a significantly lower level of hemolymph trehalose, even
      though HTH is exogenously administered. Paraquat elicits lethal oxidative stress
      in B. germanica, and co-injection of paraquat and HTH reduces this detrimental
      effect and extends the median survival time. Interestingly, the "rescue" effect
      of HTH on mortality caused by paraquat is diminished in specimens with depleted
      expression of Blage-HTH and Blage-HTHR. Finally, lipid peroxidation in the
      hemolymph increases 4 h after paraquat treatment, in comparison with control
      specimens or with HTH-treated specimens. However, lipid peroxidation induced by
      paraquat was not "rescued" by HTH in Blage-HTH and Blage-HTHR knockdown
      specimens. Our results demonstrate that HTH acts as a stress hormone mediating
      anti-oxidative protection in B. germanica, and that its receptor, Blage-HTHR, is
      essential for this action.

PMID- 22649401
TI  - The Heat is on: A New Avenue to Study Brown Fat Formation in Humans.

PMID- 22649402
TI  - Low affinity GPCRs for metabolic intermediates: challenges for pharmacologists.
AB  - The discovery that a number of metabolites and metabolic intermediates can act
      through G protein-coupled receptors has attracted great interest in the field and
      has led to new therapeutic targets for diseases such as hypertension, type 2
      diabetes, inflammation, and metabolic syndrome. However, the low apparent
      affinity of these ligands for their cognate receptors poses a number of
      challenges for pharmacologists interested in investigating receptor structure,
      function or physiology. Furthermore, the endogenous ligands matched to their
      receptors have other, well established metabolic roles and thus selectivity is
      difficult to achieve. This review discusses some of the issues researchers face
      when working with these receptors and highlights the ways in which a number of
      these obstacles have been overcome.

PMID- 22649403
TI  - Effects of starvation on brain short neuropeptide F-1, -2, and -3 levels and
      short neuropeptide F receptor expression levels of the silkworm, Bombyx mori.
AB  - In our previous report, we demonstrated the possibility that various regulatory
      neuropeptides influence feeding behavior in the silkworm, Bombyx mori. Among
      these feeding-related neuropeptides, short neuropeptide F (sNPF) exhibited
      feeding-accelerating activity when injected into B. mori larvae. Like other
      insect sNPFs, the deduced amino acid sequence of the cDNA encoding the sNPF
      precursor appears to produce multiple sNPF and sNPF-related peptides in B. mori.
      The presence of three sNPFs, sNPF-1, sNPF-2, and sNPF-3, in the brain of B. mori
      larvae was confirmed by direct MALDI-TOF mass spectrometric profiling. In
      addition, all three sNPFs are present in other larval ganglia. The presence of
      sNPF mRNA in the central nervous system (CNS) was also confirmed by Reverse
      transcription-polymerase chain reaction. Semi-quantitative analyses of sNPFs in
      the larval brain using matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry further revealed that brain sNPF levels decrease in response to
      starvation, and that they recover with the resumption of feeding. These data
      suggest that sNPFs were depleted by the starvation process. Furthermore, food
      deprivation decreased the transcriptional levels of the sNPF receptor (BNGR-A10)
      in the brain and CNS, suggesting that the sNPF system is dependent on the feeding
      state of the insect and that the sNPF system may be linked to locomotor activity
      associated with foraging behavior. Since the injection of sNPFs accelerated the
      onset of feeding in B. mori larvae, we concluded that sNPFs are strongly related
      to feeding behavior. In addition, semi-quantitative MS analyses revealed that
      allatostatin, which is present in the larval brain, is also reduced in response
      to starvation, whereas the peptide level of Bommyosuppressin was not affected by
      different feeding states.

PMID- 22649406
TI  - Fluvoxamine attenuated endoplasmic reticulum stress-induced leptin resistance.
AB  - Increasing evidence indicates that endoplasmic reticulum stress (ER stress) is
      involved in the development of metabolic syndrome. However, pharmacological
      treatments targeting ER stress are not well understood. In the present study, we
      found that fluvoxamine, a selective serotonin reuptake inhibitor used for
      depression, can attenuate ER stress-induced "leptin resistance," i.e.,
      insensitivity to the anti-obesity hormone leptin. Treatment with tunicamycin, an
      ER stress-inducing reagent, caused cell death which was significantly inhibited
      by fluvoxamine. Leptin activates JAK2-STAT3 signaling. ER stress caused an
      impairment of leptin-induced STAT3 phosphorylation which was reversed by
      fluvoxamine. Fluvoxamine would be a novel leptin-sensitizing drug, which targets
      ER stress.

PMID- 22649405
TI  - Melanocortin systems on pigment dispersion in fish chromatophores.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH) is responsible for pigment
      dispersion in the chromatophores of fish and other tetrapods such as amphibians
      and reptiles. Recently, we discovered that alpha-MSH did not always stimulate
      pigment dispersion because this hormonal peptide exerted no effects on the
      melanophores of flounders. We assumed that the reduction of alpha-MSH activity
      was related to the co-expression of different alpha-MSH receptor subtypes -
      termed melanocortin receptors (MCR) - a member of G-protein-coupled receptors
      (GPCR) - based on several reports demonstrating that GPCR forms heterodimers with
      various properties that are distinct from those of the corresponding monomers. In
      this review, we summarize the relationships between the pigment-dispersing
      activity of alpha-MSH-related peptides, molecular forms of alpha-MSH-related
      peptides, and mcr subtypes expressed in fish chromatophores.

PMID- 22649407
TI  - PAZ6 cells constitute a representative model for human brown pre-adipocytes.
AB  - The role of brown adipose tissue (BAT) in human metabolism and its potential as
      an anti-obesity target organ have recently received much renewed attention.
      Following radiological detection of substantial amounts of BAT in adults by
      several independent research groups, an increasing number of studies are now
      dedicated to uncover BAT's genetic, developmental, and environmental
      determinants. In contrast to murine BAT, human BAT is not present as a single
      major fat depot in a well-defined location. The distribution of BAT in several
      areas in the body significantly limits its availability to research. A human
      brown adipocyte cell line is therefore critical in broadening the options
      available to researchers in the field. The human BAT-cell line PAZ6 was created
      to address such a need and has been well characterized by several research groups
      around the world. In the present review, we discuss their findings and propose
      potential applications of the PAZ6 cells in addressing the relevant questions in
      the BAT field, namely for future use in therapeutic applications.

PMID- 22649408
TI  - Assessment of oxidative metabolism in brown fat using PET imaging.
AB  - OBJECTIVE: Although it has been believed that brown adipose tissue (BAT) depots
      disappear shortly after the perinatal period in humans, positron emission
      tomography (PET) imaging using the glucose analog 18F-deoxy-d-glucose (FDG) has
      shown unequivocally the existence of functional BAT in humans, suggesting that
      most humans have some functional BAT. The objective of this study was to
      determine, using dynamic oxygen-15 (15O) PET imaging, to what extent BAT
      thermogenesis is activated in adults during cold stress and to establish the
      relationship between BAT oxidative metabolism and FDG tracer uptake. METHODS:
      Fourteen adult normal subjects (9F/5M, 30 +/- 7 years) underwent triple oxygen
      scans (H215O, C15O, 15O2) as well as indirect calorimetric measurements at both
      rest and following exposure to mild cold (16 degrees C). Subjects were divided
      into two groups (BAT+ and BAT-) based on the presence or absence of FDG tracer
      uptake (SUV > 2) in cervical-supraclavicular BAT. Blood flow and oxygen
      extraction fraction (OEF) was calculated from dynamic PET scans at the location
      of BAT, muscle, and white adipose tissue (WAT). The metabolic rate of oxygen
      (MRO2) in BAT was determined and used to calculate the contribution of activated
      BAT to daily energy expenditure (DEE). RESULTS: The median mass of activated BAT
      in the BAT+ group (5F, age 31 +/- 8) was 52.4 g (range 14-68 g) and was 1.7 g
      (range 0-6.3 g) in the BAT - group (5M/4F, age 29 +/- 6). Corresponding SUV
      values were significantly higher in the BAT+ as compared to the BAT- group (7.4
      +/- 3.7 vs. 1.9 +/- 0.9; p = 0.03). Blood flow values in BAT were significantly
      higher in the BAT+ group as compared to the BAT- group (13.1 +/- 4.4 vs. 5.7 +/-
      1.1 ml/100 g/min, p = 0.03), but were similar in WAT (4.1 +/- 1.6 vs. 4.2 +/- 1.8
      ml/100 g/min) and muscle (3.7 +/- 0.8 vs. 3.3 +/- 1.2 ml/100 g/min). Moreover,
      OEF in BAT was similar in the two groups (0.56 +/- 0.18 in BAT+ vs. 0.46 +/- 0.19
      in BAT-, p = 0.39). Calculated MRO(2) values in BAT increased from 0.95 +/- 0.74
      to 1.62 +/- 0.82 ml/100 g/min in the BAT+ group and were significantly higher
      than those determined in the BAT- group (0.43 +/- 0.27 vs. 0.56 +/- 0.24, p =
      0.67). The DEE associated with BAT oxidative metabolism was highly variable in
      the BAT+ group, with an average of 5.5 +/- 6.4 kcal/day (range 0.57-15.3
      kcal/day). CONCLUSION: BAT thermogenesis in humans accounts for less than 20
      kcal/day during moderate cold stress, even in subjects with relatively large BAT
      depots. Furthermore, due to the large differences in blood flow and glucose
      metabolic rates in BAT between humans and rodents, the application of rodent data
      to humans is problematic and needs careful evaluation.

PMID- 22649409
TI  - Dehydroepiandrosterone biosynthesis, role, and mechanism of action in the
      developing neural tube.
AB  - Dehydroepiandrosterone (DHEA) is synthesized from cholesterol by activity of
      P450scc and P450c17, enzymes that we previously characterized in the developing
      nervous system. We describe the localization of P450c17 in the differentiated
      field of the ventral spinal cord in different motor neuron subtypes. We show
      that, during organogenesis, P450c17 activity is regulated along the
      antero/posterior axis of the spinal cord concomitantly with the gradient of
      neurogenesis. To examine whether DHEA may modulate this process, we measured
      proliferation and differentiation of ventral neural precursors in primary and
      explant cultures. Our results showed that DHEA-induced the expression of class II
      protein Nkx6.1, motor neuron precursor Olig-2, and definitive motor neuron marker
      Isl-1/2. DHEA also promoted proliferation of ventrally committed precursors in
      isolated spinal cord precursor cultures and in whole spinal cord explants. Both
      the proliferative and inductive effects of DHEA were dependent on sonic hedgehog
      signaling. The possibilities that the effects observed with DHEA were due to its
      metabolism into androgens or to activation of NMDA receptors were excluded. These
      results support the hypothesis that the tight regulation of DHEA biosynthesis may
      be a biologic clock restricting the period of ventral neuronal-precursor
      proliferation, thus controlling the number of pre-committed neurons in the
      developing neural tube.

PMID- 22649404
TI  - Progesterone signaling mechanisms in brain and behavior.
AB  - Steroid hormone, progesterone, modulates neuroendocrine functions in the central
      nervous system resulting in alterations in physiology and behavior. These
      neuronal effects are mediated primarily by intracellular progestin receptors
      (PRs) in the steroid-sensitive neurons, resulting in transcription-dependent
      genomic actions (classical mechanism). In addition to progesterone, intracellular
      PRs can also be activated in a "ligand-independent" manner by neurotransmitters,
      peptide growth factors, cyclic nucleotides, and neurosteroids. Recent studies
      indicate that rapid, non-classical progesterone actions involving cytoplasmic
      kinase signaling and/or extranuclear PRs can result in both transcription
      independent and transcription-dependent actions. Cross-talk between extranuclear
      and classical intracellular signaling pathways promotes progesterone-dependent
      behavior in mammals. This review focuses on the mechanisms by which progesterone
      initiated signaling mechanisms converge with PRs in the brain to modulate
      reproductive behavior in female rodents.

PMID- 22649411
TI  - The succinate receptor as a novel therapeutic target for oxidative and metabolic
      stress-related conditions.
AB  - The succinate receptor (also known as GPR91) is a G protein-coupled receptor that
      is closely related to the family of P2Y purinoreceptors. It is expressed in a
      variety of tissues, including blood cells, adipose tissue, the liver, retina, and
      kidney. In these tissues, this receptor and its ligand succinate have recently
      emerged as novel mediators in local stress situations, including ischemia,
      hypoxia, toxicity, and hyperglycemia. Amongst others, the succinate receptor is
      involved in recruitment of immune cells to transplanted tissues. Moreover, it was
      shown to play a key role in the development of diabetic retinopathy. However,
      most prominently, the role of locally increased succinate levels and succinate
      receptor activation in the kidney, stimulating the systemic and local renin
      angiotensin system, starts to unfold: the succinate receptor is a key mediator in
      the development of hypertension and possibly fibrosis in diabetes mellitus and
      metabolic syndrome. This makes the succinate receptor a promising drug target to
      counteract or prevent cardiovascular and fibrotic defects in these expanding
      disorders. Recent development of SUCNR1-specific antagonists opens novel
      possibilities for research in models for these disorders and may eventually
      provide novel opportunities for the treatment of patients.

PMID- 22649410
TI  - Insulin analogs and cancer.
AB  - Today, insulin analogs are used in millions of diabetic patients. Insulin analogs
      have been developed to achieve more physiological insulin replacement in terms of
      time-course of the effect. Modifications in the amino acid sequence of the
      insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs
      in respect to human insulin. However, these changes can also modify the molecular
      and biological effects of the analogs. The rapid-acting insulin analogs, lispro,
      aspart, and glulisine, have a rapid onset and shorter duration of action. The
      long-acting insulin analogs glargine and detemir have a protracted duration of
      action and a relatively smooth serum concentration profile. Insulin and its
      analogs may function as growth factors and therefore have a theoretical potential
      to promote tumor proliferation. A major question is whether analogs have an
      increased mitogenic activity in respect to insulin. These ligands can promote
      cell proliferation through many mechanisms like the prolonged stimulation of the
      insulin receptor, stimulation of the IGF-1 receptor (IGF-1R), prevalent
      activation of the extracellular-signaling-regulated kinase (ERK) rather than the
      protein kinase B (PKB/AKT) intracellular post-receptor pathways. Studies on in
      vitro models indicate that short-acting analogs elicit molecular and biological
      effects that are similar to those of insulin. In contrast, long-acting analogs
      behave differently. Although not all data are homogeneous, both glargine and
      detemir have been found to have a decreased binding to receptors for insulin but
      an increased binding to IGF-1R, a prevalent activation of the ERK pathway, and an
      increased mitogenic effect in respect to insulin. Recent retrospective
      epidemiological clinical studies have suggested that treatment with long-acting
      analogs (specifically glargine) may increase the relative risk for cancer.
      Results are controversial and methodologically weak. Therefore prospective
      clinical studies are needed to evaluate the possible tumor growth-promoting
      effects of these insulin analogs.

PMID- 22649412
TI  - Bariatric surgery in hypothalamic obesity.
AB  - Craniopharyngiomas (CP) are epithelial neoplasms generally found in the area of
      the pituitary and hypothalamus. Despite benign histology, these tumors and/or
      their treatment often result in significant, debilitating disorders of endocrine,
      neurological, behavioral, and metabolic systems. Severe obesity is observed in a
      high percentage of patients with CP resulting in significant comorbidities and
      negatively impacting quality of life. Obesity occurs as a result of hypothalamic
      damage and disruption of normal homeostatic mechanisms regulating energy balance.
      Such pathological weight gain, termed hypothalamic obesity (HyOb), is often
      severe and refractory to therapy. Unfortunately, neither lifestyle intervention
      nor pharmacotherapy has proven effective in the treatment of HyOb. Given the
      limited choices and poor results of these treatments, several groups have
      examined bariatric surgery as a treatment alternative for patients with CP-HyOb.
      While a large body of evidence exists supporting the use of bariatric surgery in
      the treatment of exogenous obesity and its comorbidities, its role in the
      treatment of HyOb has yet to be defined. To date, the existing literature on
      bariatric surgery in CP-HyOb is largely limited to case reports and series with
      short term follow-up. Here we review the current reports on the use of bariatric
      surgery in the treatment of CP-HyOb. We also compare these results to those
      reported for other populations of HyOb, including Prader-Willi Syndrome, Bardet
      Biedl syndrome, and hypothalamic melanocortin signaling defects. While initial
      reports of bariatric surgery in CP-HyOb are promising, their limited scope makes
      it difficult to draw any substantial conclusions as to the long term safety and
      efficacy of bariatric surgery in CP-HyOb. There continues to be a need for more
      robust, controlled, prospective studies with long term follow-up in order to
      better define the role of bariatric surgery in the treatment of HyOb.

PMID- 22649415
TI  - Construction of an in vivo system for functional analysis of the genes involved
      in sex pheromone production in the silkmoth, Bombyx mori.
AB  - Moths produce species-specific sex pheromones to attract conspecific mates. The
      biochemical processes that comprise sex pheromone biosynthesis are precisely
      regulated and a number of gene products are involved in this biosynthesis and
      regulation. In recent years, at least 300 EST clones have been isolated from
      Bombyx mori pheromone gland (PG) specific cDNA libraries with some of those
      clones [i.e., B. mori PG-specific desaturase 1 (Bmpgdesat1), PG-specific fatty
      acyl reductase, PG-specific acyl-CoA-binding protein, B. mori fatty acid
      transport protein, B. mori lipid storage droplet protein-1] characterized and
      demonstrated to play a role in sex pheromone production. However, most of the EST
      clones have yet to be fully characterized and identified. To develop an efficient
      system for analyzing sex pheromone production-related genes, we investigated the
      feasibility of a novel gene analysis system using the upstream region of
      Bmpgdesat1 that should contain a PG-specific gene promoter in conjunction with
      piggyBac vector-mediated germ line transformation. As a result, we have been able
      to obtain expression of our reporter gene (enhanced green fluorescent protein) in
      the PG but not in other tissues of transgenic B. mori. Current results indicate
      that we have successfully constructed a novel in vivo gene analysis system for
      sex pheromone production in B. mori.

PMID- 22649413
TI  - Sense and nonsense in metabolic control of reproduction.
AB  - An exciting synergistic interaction occurs among researchers working at the
      interface of reproductive biology and energy homeostasis. Reproductive biologists
      benefit from the theories, experimental designs, and methodologies used by
      experts on energy homeostasis while they bring context and meaning to the study
      of energy homeostasis. There is a growing recognition that identification of
      candidate genes for obesity is little more than meaningless reductionism unless
      those genes and their expression are placed in a developmental, environmental,
      and evolutionary context. Reproductive biology provides this context because
      metabolic energy is the most important factor that controls reproductive success
      and gonadal hormones affect energy intake, storage, and expenditure. Reproductive
      hormone secretion changes during development, and reproductive success is key to
      evolutionary adaptation, the process that most likely molded the mechanisms that
      control energy balance. It is likely that by viewing energy intake, storage, and
      expenditure in the context of reproductive success, we will gain insight into
      human obesity, eating disorders, diabetes, and other pathologies related to fuel
      homeostasis. This review emphasizes the metabolic hypothesis: a sensory system
      monitors the availability of oxidizable metabolic fuels and orchestrates
      behavioral motivation to optimize reproductive success in environments where
      energy availability fluctuates or is unpredictable.

PMID- 22649414
TI  - Do the interactions between glucocorticoids and sex hormones regulate the
      development of the metabolic syndrome?
AB  - The metabolic syndrome is basically a maturity-onset disease. Typically, its
      manifestations begin to flourish years after the initial dietary or environmental
      aggression began. Since most hormonal, metabolic, or defense responses are
      practically immediate, the procrastinated response do not seem justified. Only in
      childhood, the damages of the metabolic syndrome appear with minimal delay. Sex
      affects the incidence of the metabolic syndrome, but this is more an effect of
      timing than absolute gender differences, females holding better than males up to
      menopause, when the differences between sexes tend to disappear. The metabolic
      syndrome is related to an immune response, countered by a permanent increase in
      glucocorticoids, which keep the immune system at bay but also induce insulin
      resistance, alter the lipid metabolism, favor fat deposition, mobilize protein,
      and decrease androgen synthesis. Androgens limit the operation of
      glucocorticoids, which is also partly blocked by estrogens, since they decrease
      inflammation (which enhances glucocorticoid release). These facts suggest that
      the appearance of the metabolic syndrome symptoms depends on the strength (i.e.,
      levels) of androgens and estrogens. The predominance of glucocorticoids and the
      full manifestation of the syndrome in men are favored by decreased androgen
      activity. Low androgens can be found in infancy, maturity, advanced age, or
      because of their inhibition by glucocorticoids (inflammation, stress, medical
      treatment). Estrogens decrease inflammation and reduce the glucocorticoid
      response. Low estrogen (infancy, menopause) again allow the predominance of
      glucocorticoids and the manifestation of the metabolic syndrome. It is postulated
      that the equilibrium between sex hormones and glucocorticoids may be a critical
      element in the timing of the manifestation of metabolic syndrome-related
      pathologies.

PMID- 22649418
TI  - Grand challenges in diabetes.

PMID- 22649416
TI  - Clinical outcome, role of BRAF(V600E), and molecular pathways in papillary
      thyroid microcarcinoma: is it an indolent cancer or an early stage of papillary
      thyroid cancer?
AB  - Most human thyroid cancers are differentiated papillary carcinomas (PTC).
      Papillary thyroid microcarcinomas (PTMC) are tumors that measure 1 cm or less.
      This class of small tumors has proven to be a very common clinical entity in
      endocrine diseases. PTMC may be present in 30-40% of human autopsies and is often
      identified incidentally in a thyroid removed for benign clinical nodules.
      Although PTMC usually has an excellent long-term prognosis, it can metastasize to
      neck lymph nodes; however deaths related to this type of thyroid tumor are very
      rare. Few data exist on molecular pathways that play a role in PTMC development;
      however, two molecules have been shown to be associated with aggressive PTMC.
      S100A4 (calcium-binding protein), which plays a role in angiogenesis,
      extracellular matrix remodeling, and tumor microenvironment, is over-expressed in
      metastatic PTMC. In addition, the BRAF(V600E) mutation, the most common genetic
      alteration in PTC, is present in many PTMC with extra thyroidal extension and
      lymph node metastasis. Importantly, recently developed selective [e.g., PLX4720,
      PLX4032 (Vemurafenib, also called RG7204)] or non-selective (e.g., Sorafenib)
      inhibitors of BRAF(V600E) may be an effective treatment for patients with
      BRAF(V600E)-expressing PTMCs with aggressive clinical-pathologic features. Here,
      we summarize the clinical outcome, cancer genetics, and molecular mechanisms of
      PTMC.

PMID- 22649419
TI  - Epigenetics modifications and therapeutic prospects in human thyroid cancer.
AB  - At present no successful treatment is available for advanced thyroid cancer,
      which comprises poorly differentiated, anaplastic, and metastatic or recurrent
      differentiated thyroid cancer not responding to radioiodine. In the last few
      years, biologically targeted therapies for advanced thyroid carcinomas have been
      proposed on the basis of the recognition of key oncogenic mutations. Although the
      results of several phase II trials look promising, none of the patients treated
      had a complete response, and only a minority of them had a partial response,
      suggesting that the treatment is, at best, effective in stabilizing patients with
      progressive disease. "Epigenetic" refers to the study of heritable changes in
      gene expression that occur without any alteration in the primary DNA sequence.
      The epigenetic processes establish and maintain the global and local chromatin
      states that determine gene expression. Epigenetic abnormalities are present in
      almost all cancers and, together with genetic changes, drive tumor progression.
      Various genes involved in the control of cell proliferation and invasion
      (p16INK4A, RASSF1A, PTEN, Rap1GAP, TIMP3, DAPK, RARbeta2, E-cadherin, and CITED1)
      as well as genes specific of thyroid differentiation (Na+/I- symport, TSH
      receptor, pendrin, SL5A8, and TTF-1) present aberrant methylation in thyroid
      cancer. This review deals with the most frequent epigenetic alterations in
      thyroid cancer and focuses on epigenetic therapy, whose goal is to target the
      chromatin in rapidly dividing tumor cells and potentially restore normal cell
      functions. Experimental data and clinical trials, especially using deacetylase
      inhibitors and demethylating agents, are discussed.

PMID- 22649420
TI  - New insights into the control of pulsatile GnRH release: the role of
      Kiss1/neurokinin B neurons.
AB  - Gonadotropin-releasing hormone (GnRH) is the ultimate output signal of an
      intricate network of neuroendocrine factors that, acting on the pituitary,
      trigger gonadotropin release. In turn, gonadotropins exert their trophic action
      on the gonads to stimulate the synthesis of sex steroids thus completing the
      gonadotropic axis through feedback regulatory mechanisms of GnRH release. These
      feedback loops are predominantly inhibitory in both sexes, leading to tonic
      pulsatile release of GnRH from puberty onward. However, in the female, rising
      levels of estradiol along the estrous cycle evoke an additional positive feedback
      that prompts a surge-like pattern of GnRH release prior to ovulation.
      Kisspeptins, secreted from hypothalamic Kiss1 neurons, are poised as major
      conduits to regulate this dual secretory pathway. Kiss1 neurons are diverse in
      origin, nature, and function, convening distinct neuronal populations in two main
      hypothalamic nuclei: the arcuate nucleus (ARC) and the anteroventral
      periventricular nucleus. Recent studies from our group and others point out Kiss1
      neurons in the ARC as the plausible generator of GnRH pulses through a system of
      pulsatile kisspeptin release shaped by the coordinated action of neurokinin B
      (NKB) and dynorphin A (Dyn) that are co-expressed in Kiss1 neurons (so-called
      KNDy neurons). In this review, we aim to document the recent findings and working
      models directed toward the identification of the Kiss1-dependent mechanisms of
      GnRH release through a synoptic overview of the state-of-the-art in the field.

PMID- 22649422
TI  - The role of IGF-1 for fracture risk in men.
AB  - Growth hormone and insulin-like growth factor-1 (IGF-1) are essential for the
      achievement of normal longitudinal bone growth and bone mass. Preclinical studies
      using various knockout models have shown that both endocrine (mostly liver
      derived) IGF-1 and bone-derived IGF-1 contribute to normal longitudinal skeletal
      growth and cortical bone size. Since bone size is an important determinant of
      bone strength, and hence fracture risk, we evaluated the predictive role of serum
      IGF-1 for fracture risk. The population-based Osteoporotic Fractures in Men
      Sweden cohort recently showed for the first time that older men with low serum
      IGF-1 levels have an increased fracture risk, especially for the two most
      important fracture types, hip and vertebral fractures. This association between
      serum IGF-1 and incident fracture risk is partly mediated via bone mineral
      density. Future studies are required to identify the mechanisms by which
      endocrine and local IGF-1 regulate skeletal growth and bone size. In addition,
      possible mediators affecting the impact of IGF-1 on fractures in men remain to be
      elucidated.

PMID- 22649421
TI  - Paracrine interactions of thyroid hormones and thyroid stimulation hormone in the
      female reproductive tract have an impact on female fertility.
AB  - Thyroid disease often causes menstrual disturbances and infertility problems.
      Thyroid hormone (TH) acts through its receptors, transcription factors present in
      most cell types in the body. Thyroid stimulating hormone (TSH) stimulates TH
      synthesis in the thyroid gland, but seems to have other functions as well in the
      female reproductive tract. The receptors of both TH and TSH increase in the
      receptive endometrium, suggesting that they are important for implantation,
      possible by influencing inflammatory mediators such as leukemia inhibitory
      factor. The roles of these receptors in the ovary need further studies. However,
      it is likely that the thyroid system is important for both follicular and embryo
      development. The association between thyroid disease and infertility indicate
      that TH and TSH affect the endometrium and ovary on the paracrine level.

PMID- 22649417
TI  - Molecular basis of signaling specificity of insulin and IGF receptors: neglected
      corners and recent advances.
AB  - Insulin and insulin-like growth factor (IGF) receptors utilize common
      phosphoinositide 3-kinase/Akt and Ras/extracellular signal-regulated kinase
      signaling pathways to mediate a broad spectrum of "metabolic" and "mitogenic"
      responses. Specificity of insulin and IGF action in vivo must in part reflect
      expression of receptors and responsive pathways in different tissues but it is
      widely assumed that it is also determined by the ligand binding and signaling
      mechanisms of the receptors. This review focuses on receptor-proximal events in
      insulin/IGF signaling and examines their contribution to specificity of
      downstream responses. Insulin and IGF receptors may differ subtly in the
      efficiency with which they recruit their major substrates (IRS-1 and IRS-2 and
      Shc) and this could influence effectiveness of signaling to "metabolic" and
      "mitogenic" responses. Other substrates (Grb2-associated binder, downstream of
      kinases, SH2Bs, Crk), scaffolds (RACK1, beta-arrestins, cytohesins), and pathways
      (non-receptor tyrosine kinases, phosphoinositide kinases, reactive oxygen
      species) have been less widely studied. Some of these components appear to be
      specifically involved in "metabolic" or "mitogenic" signaling but it has not been
      shown that this reflects receptor-preferential interaction. Very few receptor
      specific interactions have been characterized, and their roles in signaling are
      unclear. Signaling specificity might also be imparted by differences in
      intracellular trafficking or feedback regulation of receptors, but few studies
      have directly addressed this possibility. Although published data are not wholly
      conclusive, no evidence has yet emerged for signaling mechanisms that are
      specifically engaged by insulin receptors but not IGF receptors or vice versa,
      and there is only limited evidence for differential activation of signaling
      mechanisms that are common to both receptors. Cellular context, rather than
      intrinsic receptor activity, therefore appears to be the major determinant of
      whether responses to insulin and IGFs are perceived as "metabolic" or
      "mitogenic."

PMID- 22649423
TI  - Vitamin D and cancer.
AB  - Vitamin D system is a complex pathway that includes precursors, active
      metabolites, enzymes, and receptors. This complex system actives several
      molecular pathways and mediates a multitude of functions. In addition to the
      classical role in calcium and bone homeostasis, vitamin D plays "non-calcemic"
      effects in host defense, inflammation, immunity, and cancer processes as
      recognized in vitro and in vivo studies. The aim of this review is to highlight
      the relationship between vitamin D and cancer, summarizing several mechanisms
      proposed to explain the potential protective effect of vitamin D against the
      development and progression of cancer. Vitamin D acts like a transcription factor
      that influences central mechanisms of tumorigenesis: growth, cell
      differentiation, and apoptosis. In addition to cellular and molecular studies,
      epidemiological surveys have shown that sunlight exposure and consequent
      increased circulating levels of vitamin D are associated with reduced reduced
      occurrence and a reduced mortality in different histological types of cancer.
      Another recent field of interest concerns polymorphisms of vitamin D receptor
      (VDR); in this context, preliminary data suggest that VDR polymorphisms more
      frequently associated with tumorigenesis are Fok1, Bsm1, Taq1, Apa1, EcoRV, Cdx2;
      although further studies are needed to clarify their role in the cancer. In this
      review, the relationship between vitamin D and cancer is discussed.

PMID- 22649424
TI  - Receptor oligomerization in family B1 of G-protein-coupled receptors: focus on
      BRET investigations and the link between GPCR oligomerization and binding
      cooperativity.
AB  - The superfamily of the seven transmembrane G-protein-coupled receptors
      (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are
      involved in the pathophysiology of numerous human diseases, and they constitute
      an estimated 30-40% of all drug targets. During the last two decades, GPCR
      oligomerization has been extensively studied using methods like bioluminescence
      resonance energy transfer (BRET) and today, receptor-receptor interactions within
      the GPCR superfamily is a well-established phenomenon. Evidence of the impact of
      GPCR oligomerization on, e.g., ligand binding, receptor expression, and signal
      transduction indicates the physiological and pharmacological importance of these
      receptor interactions. In contrast to the larger and more thoroughly studied GPCR
      subfamilies A and C, the B1 subfamily is small and comprises only 15 members,
      including, e.g., the secretin receptor, the glucagon receptor, and the receptors
      for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1
      receptors is involved in diseases, such as diabetes, chronic inflammation, and
      osteoporosis which underlines the pathophysiological importance of this GPCR
      subfamily. In spite of this, investigation of family B1 receptor oligomerization
      and especially its pharmacological importance is still at an early stage. Even
      though GPCR oligomerization is a well-established phenomenon, there is a need for
      more investigations providing a direct link between these interactions and
      receptor functionality in family B1 GPCRs. One example of the functional effects
      of GPCR oligomerization is the facilitation of allosterism including
      cooperativity in ligand binding to GPCRs. Here, we review the currently available
      data on family B1 GPCR homo- and heteromerization, mainly based on BRET
      investigations. Furthermore, we cover the functional influence of oligomerization
      on ligand binding as well as the link between oligomerization and binding
      cooperativity.

PMID- 22649425
TI  - FoxA1 is a key mediator of hormonal response in breast and prostate cancer.
AB  - Hormonally regulated breast and prostate cancers are the most common cause of
      cancer in females and males respectively. FoxA1 acts as a pioneer factor for both
      androgen receptor (AR) and estrogen receptor-alpha (ER), dictating the binding
      location, and therefore function of these transcription factors. It is an
      essential protein for the transcriptional activity of both ER and AR, yet it has
      distinct roles with the two different nuclear receptors. In both malignancies,
      FoxA1 plays a pivotal role from early stage cancer through to drug resistant and
      metastatic disease. Due to this key role in mediating ER and AR function, FoxA1
      is not only an attractive therapeutic target but could potentially function as a
      novel biomarker.

PMID- 22649426
TI  - The genomic landscape of prostate cancer.
AB  - Prostate cancer is a common malignancy in men, with a markedly variable clinical
      course. Somatic alterations in DNA drive the growth of prostate cancers and may
      underlie the behavior of aggressive versus indolent tumors. The accelerating
      application of genomic technologies over the last two decades has identified
      mutations that drive prostate cancer formation, progression, and therapeutic
      resistance. Here, we discuss exemplary somatic mutations in prostate cancer, and
      highlight mutated cellular pathways with biological and possible therapeutic
      importance. Examples include mutated genes involved in androgen signaling, cell
      cycle regulation, signal transduction, and development. Some genetic alterations
      may also predict the clinical course of disease or response to therapy, although
      the molecular heterogeneity of prostate tumors poses challenges to genomic
      biomarker identification. The widespread application of massively parallel
      sequencing technology to the analysis of prostate cancer genomes should continue
      to advance both discovery-oriented and diagnostic avenues.

PMID- 22649428
TI  - Of genes and genomes: challenges for the twenty-first century.

PMID- 22649427
TI  - Physical activity: the forgotten tool for type 2 diabetes management.
AB  - Individuals who are currently sedentary, unfit, or overweight can benefit
      metabolically from simply taking breaks from sitting. Since avoidance of
      sedentary behavior appears to have a large impact on glycemic management, all
      individuals with type 2 diabetes should be encouraged to minimally engage in
      greater daily movement to better manage their diabetes and body weight. In
      addition, engaging in physical activity of any intensity (including low-intensity
      ones) likely positively impacts insulin action and blood glucose control acutely.
      Moreover, as long as total caloric expenditure during exercise is matched (i.e.,
      total exercise dose), daily exercise may be done every other day instead with the
      same glycemic results, although at least 150 min of weekly physical activity is
      recommended. Both aerobic and resistance training are important for individuals
      with diabetes, and ideally a program that combines the two types of training
      should be undertaken to achieve maximal glycemic and other benefits. Once
      individuals have successfully implemented more daily movement into their
      lifestyle, they will be more likely to participate in structured forms of
      physical activity to gain additional benefits. All clinicians working with
      individuals with either type 2 diabetes or prediabetes should consider
      incorporating these suggestions into care plans to improve their patients'
      glycemic management.

PMID- 22649429
TI  - Cerebrospinal Fluid Alzheimer Markers in Depressed Elderly Subjects with and
      without Alzheimer's Disease.
AB  - BACKGROUND: The aim of this study was to explore the relationship between
      cerebrospinal fluid Alzheimer's disease (AD) markers and depression in elderly
      people. METHOD: We included subjects with AD as well as persons with subjective
      cognitive impairment and normal cognition. Depression was assessed with the
      Cornell Scale for Depression in Dementia, and a cut-off score of >6 was used to
      define depression. Cerebrospinal fluid was analyzed using commercially available
      assays for beta-amyloid 1-42, total tau, and phosphorylated tau 181. RESULTS: A
      total of 183 participants (66.7% female) were included (92 with AD and 91 with
      subjective cognitive impairment), with a mean age (+/-SD) of 67.6 +/- 7.4 years,
      a Mini-Mental State Examination score of 26.0 +/- 4.0, and a median Cornell Scale
      for Depression in Dementia score of 5 (range 0-19). Depression scores were not
      associated with higher phosphorylated tau 181 and total tau or reduced beta
      amyloid 1-42 in AD or non-demented subjects. CONCLUSIONS: These results suggest
      that AD pathology does not contribute to depression, indicating that other
      factors may be more important. Further studies of the aetiology of depression in
      elderly people with and without AD are warranted.

PMID- 22649430
TI  - Putting back basic sciences, political economy and sexuality into health.

PMID- 22649431
TI  - Inhibitors caveolin-1 and protein kinase G show differential subcellular
      colocalization with Nitric oxide synthase.
AB  - BACKGROUND: Nitric oxide synthase (NOS) is negatively regulated by protein
      protein interactions with caveolin-1 before extracellular activating signals
      release it for nitric oxide (NO) production. Smooth muscle protein kinase G (PKG)
      is a down-stream effector of NO signaling for relaxation of vascular smooth
      muscle cells (SMC). The PKG is also found in endothelial cells and it inhibits
      activated NOS within endothelial cells. METHODS: We used confocal fluorescence
      microscopy to colocalize the inhibitors caveolin-1 and PKG with NOS in freshly
      isolated neonatal lamb endothelial cells in order to corroborate the speculation
      of their differential effects on NOS. The roles of caveolin-1 and PKG as
      regulators of NOS were investigated by examining their respective subcellular
      sites of colocalization with NOS using qualitative fluorescence
      immunohistochemistry and confocal microscopy. RESULTS: Caveolin-1 was colocalized
      with NOS in the plasma membrane and Golgi. The PKG1-beta isoform was colocalized
      with serine116 phosphorylated NOS in the cytosol and in vesicular structures seen
      in the endoplasmic reticulum and in the nuclear region. CONCLUSION: We conclude
      that unlike caveolin-1, a known pre-activation inhibitor of nascent NOS, PKG may
      be a post-activation inhibitor of NOS, possibly important for the recycling of
      the spent enzyme.

PMID- 22649432
TI  - Factors associated with contracting sexually transmitted infections among
      patients in Zvishavane urban, Zimbabwe; 2007.
AB  - BACKGROUND: Sexually transmitted infections (STIs) remain a major public health
      problem in Zimbabwe. In Zvishavane, STI increased from 66 per 1,000 in 2002 to 97
      per 1,000 in 2005, a 31% increase in cases. OBJECTIVE: To determine the factors
      associated with contracting sexually transmitted infections (STI) among patients
      in Zvishavane. METHODS: A frequency matched case control study was conducted.
      Cases were persons above 15 years diagnosed with STI at three health facilities
      in Zvishavane urban. Controls were patients who visited the same facilities for
      other ailments. We interviewed 77 cases and 154 controls. RESULTS: Both cases and
      controls were knowledgeable about STI. Risk factors for men included sex under
      the influence of alcohol OR=7.11 (95% CI 2.42-20.85), relationships less than one
      year, OR= 9.33 (95% CI 3.53-24.70), no condom use at first intercourse OR=5.17
      (95% CI 1.64-16.25) and paying for sex OR= 23.65 (95% CI 6.23-89.69). For females
      the risk factors were non-use of condom at first intercourse OR=2.49 (95% CI 1.02
      6.04) and relationships less than one year OR=3.19 (95% CI 1.41-7.23).
      Significant differences in attitudes were evident among cases and controls.
      CONCLUSION: Knowledge of STI did not provide protection from STI diagnosis.
      Limiting the number of partners, consistent condom use, and fidelity are
      important for both men and women.

PMID- 22649433
TI  - Level of stigma among female sex workers: comparison of two surveys of HIV
      behavioral data, Ethiopia.
AB  - BACKGROUND: HIV and AIDS stigma and discrimination is widespread in Africa. We
      did a secondary data analysis of HIV and AIDS behavioral surveillance surveys
      (BSS) on female sex workers residing in three major cities in Ethiopia.
      OBJECTIVES: To compare level of sigma among sex workers through the analysis of
      two data sources of BSS conducted in 2002 and 2005 in Ethiopia. METHODS: The BSS
      used standardized methodology to study the level of stigma among female sex
      workers. Female sex workers were sampled using two-stage probability sampling
      methods in each of the three cities. Data from a total of 2,888 female sex
      workers was analyzed and interpreted. We used Chi square to compare the socio
      demographic variables of the two surveys and logistic regression to compare level
      of stigma between the two surveys. RESULTS: There is a significant difference in
      the level of stigma between the two surveys. This applies to most of the
      questions that were included in the surveys. CONCLUSION: The proportion of female
      sex workers with a stigmatizing attitude is considerably high, posing threats to
      the HIV prevention program. Strengthening interventions on all aspects of stigma
      is recommended.

PMID- 22649434
TI  - Impact of male circumcision on HIV risk compensation through the impediment of
      condom use in Botswana.
AB  - BACKGROUND: Male circumcision has been recommended as a method of reducing the
      risk of transmitting HIV. However, widespread uptake of male circumcision may
      lead to HIV risk compensation by impeding condom use. OBJECTIVE: To investigate
      the impact of male circumcision on condom use. METHODS: The study used cross
      sectional data from the Botswana AIDS Impact Survey III on 1,257 men aged 15
      years or older who were sexually active. Data were analyzed using Pearson's chi
      square statistic and binary logistic regression. RESULTS: The study found that
      15% of circumcised men did not use condoms compared to 12% of uncircumcised men,
      and circumcision was not significantly associated with condom use. Non-use of
      condoms was significantly affected by religious beliefs, low level of education,
      marriage, drunkenness, and misconceptions regarding antiretroviral therapy (ART).
      CONCLUSIONS: We conclude that male circumcision does not impede condom use.
      Condom use is impeded by low level of education, marriage, drunkenness, and
      misconceptions regarding ART. We recommend the emphasis of consistent condom use
      targeting people with low education, those in marriage, users of alcohol, and
      people receiving ART.

PMID- 22649435
TI  - Social predictors of caesarean section births in Italy.
AB  - BACKGROUND: Caesarean section birth is a frequent mode of delivery worldwide.
      Several social factors have been demonstrated to be strong predictors of
      caesarean births. OBJECTIVES: To identify possible social predictors of caesarean
      section births in Italy. METHODS: Data for this study were drawn from the Italian
      Institute of Statistics (ISTAT) survey conducted during year 2005 which comprised
      a nationally representative sample of 50,474 households (128,040 subjects). This
      2005 ISTAT survey asked several questions to women who delivered (n=5,812) in the
      past five years prior to the survey about their delivery mode. The main dependent
      variables were caesarean delivery rates while independent variables included
      sociodemographics, health and health-related factors. Descriptive statistics,
      bivariate and multivariate analyses were performed. RESULTS: Our sample comprised
      5,812 women. Rate of caesarean deliveries was 36.2 percent. Age (adjOR: 0.961;
      p=0.000) and residence (Reference: North-West; Centre: adjOR: 0.753, p=0.001;
      South: adjOR: 0.484, p=0.000; Islands: adjOR: 0.629, p=0.000) were the sole
      social factors which were significant in predicting caesarean delivery (adjusted
      model). CONCLUSIONS: Rate of caesarean delivery in Italy is rather high. Age and
      residence are the sole social predictors evidenced from the ISTAT 2005 survey
      data.

PMID- 22649436
TI  - Plasma vitamin C concentration in pregnant women with pre-eclampsia in Mulago
      hospital, Kampala, Uganda.
AB  - BACKGROUND: Oxidative stress plays a role in the aetiology of pre-eclampsia and
      vitamin C may prevent pre-eclampsia. OBJECTIVE: To determine the association
      between plasma vitamin C and pre-eclampsia in Mulago Hospital, Kampala, Uganda.
      METHODS: This case-control study was conducted at Mulago Hospital from 1(st) May
      2008 to 1(st) May 2009; 207 women were the cases and 352 women were the controls.
      Plasma vitamin C was assayed in the women using a colorimetric method. An
      independent t test was used to find the difference in the means of plasma vitamin
      C and logistic regression was used to find the association between plasma vitamin
      C and pre-eclampsia. RESULTS: The mean plasma vitamin C was 1.7(SD=0.7) * 10(3)
      ug/L in women with pre-eclampsia and 1.9(SD=0.7) * 10(3) ug/L in women with
      normal pregnancy (P=0.005). Women with low plasma vitamin C were at an increased
      risk of pre-eclampsia (OR 2.91, 95% CI: 1.56-5.44). CONCLUSION: There was a
      strong association between low plasma vitamin C, and pre-eclampsia in women
      attending antenatal clinics at Mulago Hospital, Kampala. Health workers need to
      advise women at risk in the antenatal period about diet, especially foods which
      are rich in vitamin C to probably reduce pre-eclampsia.

PMID- 22649437
TI  - Knowledge and utilization of malaria control measures by pregnant and newly
      delivered mothers in Ibadan, Nigeria.
AB  - BACKGROUND: The World Health Organisation (WHO) guidelines for the control of
      malaria during pregnancy include prompt and effective case management of malaria
      combined with prevention of infection by insecticide-treated nets (ITNs) and
      intermittent preventive treatment in pregnancy (IPTp). Despite this the uptake is
      poor. OBJECTIVE: To describe the malaria prevention measures utilized by these
      women in this environment. METHODS: Information was obtained from consented
      pregnant and newly delivered women on their socio-demographic characteristics,
      knowledge and use of malaria chemoprophylaxis RESULTS: One Thousand three hundred
      thirty (1330) pregnant and newly delivered women in 132 facilities within the
      Ibadan metropolis were surveyed. The mean age of the respondents was 29. 67 years
      (+/-5.21). The modes of prevention most commonly reported as being effective were
      the use of insecticide spray, window nets and ITN. Only 28.2% were using ITNs in
      the index pregnancy, and 67.2% of the women had had a drug administered for
      prophylactic purposes in the index pregnancy. CONCLUSION: This study demonstrates
      awareness but poor use of control measures. Additionally, there is poor use of
      the recommended agent for IPT. The factors militating against the use of these
      preventive measures need to be urgently explored and addressed.

PMID- 22649438
TI  - Analyzing the influence of institutions on health policy development in Uganda: a
      case study of the decision to abolish user fees.
AB  - BACKGROUND: During the 2001 election campaign, President Yoweri Museveni
      announced he was abolishing user fees for health services in Uganda. No analysis
      has been carried out to explain how he was able to initiate such an important
      policy decision without encountering any immediate barriers. OBJECTIVE: To
      explain this outcome through in-depth policy analysis driven by the application
      of key analytical frameworks. METHODS: An explanatory case study informed by
      analytical frameworks from the institutionalism literature was undertaken.
      Multiple data sources were used including: academic literature, key government
      documents, grey literature, and a variety of print media. RESULTS: According to
      the analytical frameworks employed, several formal institutional constraints
      existed that would have reduced the prospects for the abolition of user fees.
      However, prevalent informal institutions such as "Big Man" presidentialism and
      clientelism that were both 'competing' and 'complementary' can be used to explain
      the policy outcome. The analysis suggests that these factors trumped the impact
      of more formal institutional structures in the Ugandan context. CONCLUSION:
      Consideration should be given to the interactions between formal and informal
      institutions in the analysis of health policy processes in Uganda, as they
      provide a more nuanced understanding of how each set of factors influence policy
      outcomes.

PMID- 22649440
TI  - The pattern, clinical characteristics and outcome of ESRD in Ile-Ife, Nigeria: is
      there a change in trend?
AB  - BACKGROUND: The prevalence of chronic renal failure and End Stage Renal Disease
      (ESRD) has remained high worldwide and the epidemiology has changed significantly
      in the last decade in industrialised countries. While there have been significant
      improvements in these patient's outcomes in developed countries, their state and
      survival is still appalling in developing countries. OBJECTIVE: To determine the
      clinical pattern, presentation and management outcomes in our ESRD population
      over a 19-year period (1989-2007). METHODS: Seven hundred and sixty patients'
      records were reviewed. Data on major causes, clinical presentation, management
      and survival were retrieved and collated. Data was analysed using SPSS package
      version 16. RESULTS: Their ages ranged between 15-90 years (mean +/- SD; 39.9+/
      1.67years) with male preponderance (70.3%). Major presenting complaints were body
      swelling and uraemic symptoms in most studied patients. The predisposing
      conditions included chronic glomerulonephritis, hypertension, obstructive
      uropathy and diabetes mellitus. Renal replacement therapy offered included HD in
      556(73.2%), Continous Ambulatory Peritoneal Dialysis (CAPD) in only 9(1.2%)
      patients and renal transplantation in only 7(0.9%). Only 38(6.8%) survived on HD
      for longer than three months while 7(77.8%) CAPD patients and all transplanted
      patients survived for between six months and four years (p<0.00001). Median
      duration of survival after diagnosis for all the patients was 2 weeks (range 0-50
      months). CONCLUSION: End stage renal disease is still prevalent with chronic
      glomerulonephritis and hypertension being the common causes. Prognosis is still
      grave hence subsidized renal replacement therapy and preventive nephrology should
      be targeted in such underserved populations.

PMID- 22649439
TI  - The efficacy of the crude root bark extracts of Erythrina abyssinica on
      rifampicin resistant Mycobacterium tuberculosis.
AB  - INTRODUCTION: Tuberculosis (TB) is one of the leading causes of morbidity and
      mortality with a global mortality rate at two million deaths per year while one
      third of the world's population is infected with the TB bacillus. OBJECTIVE: To
      determine the efficacy of the crude extracts of Erythrina abyssinica root bark on
      rifampicin-resistant TB. METHODS: Crude extracts of root bark of Erythrina
      abyssinica, were screened against three strains of Mycobacterium tuberculosis
      including rifampicin-resistant TMC-331. Susceptibility tests used the disc
      diffusion method and were done on solid Middle brook 7H10, while the Minimum
      Inhibitory concentration (MICs) and minimum bactericidal concentration (MBCs)
      were determined by the Microtitre plate method using Middle brook 7H9 broth.
      RESULTS: The total crude methanol extract showed activity against all the three
      strains of mycobacterium used, at 50mg/ml and diameters of zones of inhibition of
      up to 26 mm. Erythrina abyssinica total crude methanol extract showed the highest
      activity on the pan sensitive strain H37Rv (0.39+/-0.0 mg/ml) and the rifampicin
      resistant strain (TMC-331) (2.35+/-1.11 mg/ ml) and was also active on
      Mycobacterium avium (0.39+/-0.mg/ml. The values for isoniazid were 0.25ug/ml and
      9.38ug/ml for H37Rv and TMC-331 respectively, while for rifampicin the MIC value
      was 0.25ug/ml for H37Rv but it was not active on TMC-331. Acute toxicity test
      gave an LD50 of 776.2mg/kg body weight while the phytochemical analysis showed
      the presence of alkaloids, tannins and flavones. CONCLUSION: The conclusion from
      the study was that Erythrina abbyssinica has antimycobacterial activity and
      reasonable safety that merits further research.

PMID- 22649442
TI  - Impact of directly observed sputum collection on sputum culture contamination
      rates.

PMID- 22649441
TI  - Withholding breast milk for HIV exposed infants in sub-Saharan Africa: benefit or
      harm?
AB  - Feeding options for HIV exposed infants has remained topical and controversial in
      most settings of sub-Saharan Africa. This commentary, expresses the author's
      opinions on this topical issue for and against breastfeeding or infant formula,
      with supporting evidence drawn from relevant literature on researches conducted
      in settings of sub-Saharan Africa. At the moment, it seems sensible to recommend
      that health care workers and policy makers should explore the options of making
      breastfeeding safer rather than withholding it for sub-Saharan African HIV
      exposed infants. It is hoped that when Highly Active Antiretroviral Therapy
      (HAART) becomes universally accessible and available to HIV infected women in sub
      Saharan Africa, breast milk HIV transmission will be a rare event and the health
      benefits of breastfeeding for the infant and mother will be maximized.

PMID- 22649444
TI  - Microwave imaging and emerging applications.

PMID- 22649443
TI  - Phenotype-genotype analysis of dystrophinopathy caused by duplication mutation in
      Dystrophin gene in an African patient.
AB  - BACKGROUND: The dystrophinopathies, duchenne muscular dystrophy (DMD) and Becker
      muscular dystrophy are common X-linked genetic myopathies resulting from
      mutations in the dystrophin gene. Duplication is an uncommon mechanism of
      mutation occurring in about 5% of DMD cases. The global prevalence of DMD is
      reported as 1/18,000 males. There is little clinical or epidemiological data on
      African patients. OBJECTIVE: To present the genotype-phenotype analysis of
      dystrophinopathy with an exon 8 through 9 duplication mutation in a patient of
      African/Ghanaian descent and his asymptomatic mother. METHODS: Investigations
      including a biopsy of the vastus lateralis muscle and genetic testing of the
      patient and his mother. RESULTS: Genetic testing demonstrated a duplication of
      exons 8 through 9 of the dystrophin gene in both the patient and his mother. The
      muscle biopsy of the patient showed partial expression of the dystrophin protein.
      In the absence of a family history of dystrophinopathy, we hypothesize that this
      is a sporadic mutation occurring in the grand maternal lineage. CONCLUSION: This
      case extends the world wide epidemiology of this disease to include the
      African/Ghanaian population and confirms the vulnerability of the dystrophin gene
      to recurrent spontaneous mutations at the exon 8 and 9 site.

PMID- 22649445
TI  - Suppression of the nuclear factor Eny2 increases insulin secretion in poorly
      functioning INS-1E insulinoma cells.
AB  - Eny2, the mammalian ortholog of yeast Sus1 and drosophila E(y)2, is a nuclear
      factor that participates in several steps of gene transcription and in mRNA
      export. We had previously found that Eny2 expression changes in mouse pancreatic
      islets during the metabolic adaptation to pregnancy. We therefore hypothesized
      that the protein contributes to the regulation of islet endocrine cell function
      and tested this hypothesis in rat INS-1E insulinoma cells. Overexpression of Eny2
      had no effect but siRNA-mediated knockdown of Eny2 resulted in markedly increased
      glucose and exendin-4-induced insulin secretion from otherwise poorly glucose
      responsive INS-1E cells. Insulin content, cellular viability, and the expression
      levels of several key components of glucose sensing remained unchanged; however
      glucose-dependent cellular metabolism was higher after Eny2 knockdown.
      Suppression of Eny2 enhanced the intracellular incretin signal downstream of
      cAMP. The use of specific cAMP analogues and pathway inhibitors primarily
      implicated the PKA and to a lesser extent the EPAC pathway. In summary, we
      identified a potential link between the nuclear protein Eny2 and insulin
      secretion. Suppression of Eny2 resulted in increased glucose and incretin-induced
      insulin release from a poorly glucose-responsive INS-1E subline. Whether these
      findings extend to other experimental conditions or to in vivo physiology needs
      to be determined in further studies.

PMID- 22649446
TI  - Male stress urinary incontinence: a review of surgical treatment options and
      outcomes.
AB  - Introduction and Objective. Iatrogenic male stress urinary incontinence (SUI)
      affects a percentage of men undergoing urologic procedures with a significant
      impact on quality of life. The treatment of male SUI has evolved significantly
      with multiple current options for treatment available. The current paper
      discusses preoperative evaluation of male SUI, available surgical options with
      reported outcomes, and postoperative complication management. Methods. A pubMed
      review of available literature was performed and summarized on articles reporting
      outcomes of placement of the artificial urinary sphincter (AUS) or male slings
      including the bone anchored sling (BAS), retrourethral transobturator sling
      (RTS), adjustable retropubic sling (ARS), and quadratic sling. Results. Reported
      rates of success (variably defined) for BAS, RTS, ARS, and AUS are 36-67%, 9-79%,
      13-100%, and 59-91% respectively. Complications reported include infection,
      erosion, retention, explantation, and transient pain. Male slings are more
      commonly performed in cases of low-to-moderate SUI with decreasing success with
      higher degrees of preoperative incontinence. Conclusions. An increasing number of
      options continue to be developed for the management of male SUI. While the AUS
      remains the gold-standard therapy for SUI, male sling placement is a proven
      viable alternative therapy for low-to-moderate SUI.

PMID- 22649447
TI  - Current Challenges in Prostate Cancer Management and the Rationale behind
      Targeted Focal Therapy.
AB  - Among men, prostate cancer has a high prevalence, with relatively lower cancer
      specific mortality risk compared to lung and colon cancer. Prostate-specific
      antigen (PSA) screening has increased prostate cancer awareness since its
      implementation as a screening tool almost 25 years ago, but, due to the largely
      indolent course of this disease and the unspecific nature of the PSA test,
      increased incidence has largely been associated with cancers that would not go on
      to cause death (clinically insignificant), leading to an overdiagnosis challenge
      and an ensuing overtreatment consequences. The overtreatment problem is
      exacerbated by the high risk of side effects that current treatment techniques
      have, putting patients' quality of life at risk with little or no survival
      benefit. The goals of this paper are to evaluate the rise, prevalence, and impact
      of the overdiagnosis and ensuing overtreatment problems, as well as highlight
      potential solutions. In this effort, a review of major epidemiological and
      screening studies, cancer statistics from the advent of prostate-specific antigen
      screening to the present, and reports on patient concerns and treatment outcomes
      was conducted to present the dominant factors that underlie current challenges in
      prostate cancer treatment and illuminate potential solutions.

PMID- 22649448
TI  - Sterol lipid metabolism in down syndrome revisited: down syndrome is associated
      with a selective reduction in serum brassicasterol levels.
AB  - Over the past 15 years, insights into sterol metabolism have improved our
      understanding of the relationship between lipids and common conditions such as
      atherosclerosis and Alzheimer's Disease (AD). A better understanding of sterol
      lipid metabolism in individuals with Down Syndrome (DS) may help elucidate how
      this population's unique metabolic characteristics influence their risks for
      atherosclerosis and AD. To revisit the question of whether sterol lipid
      parameters may be altered in DS subjects, we performed a pilot study to assess
      traditional serum sterol lipids and lipoproteins, as well as markers of sterol
      biosynthesis, metabolites, and plant sterols in 20 subjects with DS compared to
      age-matched controls. Here we report that the levels of nearly all lipids and
      lipoproteins examined are similar to control subjects, suggesting that trisomy 21
      does not lead to pronounced general alterations in sterol lipid metabolism.
      However, the levels of serum brassicasterol were markedly reduced in DS subjects.

PMID- 22649449
TI  - Physiologically based toxicokinetic modelling as a tool to support risk
      assessment: three case studies.
AB  - In this contribution we present three case studies of physiologically based
      toxicokinetic (PBTK) modelling in regulatory risk assessment. (1) Age-dependent
      lower enzyme expression in the newborn leads to bisphenol A (BPA) blood levels
      which are near the levels of the tolerated daily intake (TDI) at the oral
      exposure as calculated by EFSA. (2) Dermal exposure of BPA by receipts, car park
      tickets, and so forth, contribute to the exposure towards BPA. However, at the
      present levels of dermal exposure there is no risk for the adult. (3) Dermal
      exposure towards coumarin via cosmetic products leads to external exposures of
      two-fold the TDI. PBTK modeling helped to identify liver peak concentration as
      the metric for liver toxicity. After dermal exposure of twice the TDI, the liver
      peak concentration was lower than that present after oral exposure with the TDI
      dose. In the presented cases, PBTK modeling was useful to reach scientifically
      sound regulatory decisions.

PMID- 22649450
TI  - Comparison of modified chandler, roller pump, and ball valve circulation models
      for in vitro testing in high blood flow conditions: application in
      thrombogenicity testing of different materials for vascular applications.
AB  - Three different models, a modified Chandler loop, roller pump, and a new ball
      valve model (Hemobile), were compared with regard to intrinsic damage of blood
      components and activation of platelets. The Hemobile was used for testing of
      polymer tubes. High flow was not possible with the Chandler loop. The roller pump
      and the Hemobile could be adjusted to high flow, but he pump induced hemolysis.
      Platelet numbers were reduced in the roller pump and Chandler loop (P < 0.05),
      but remained high in the Hemobile. Platelet aggregation was reduced in all
      models. The Hemobile was applied for testing vascular graft materials, and
      allowed different circuits circulated simultaneously at 37 degrees C. ePTFE,
      Dyneema Purity UHMWPE fiber and PET fiber based tubes, all showed hemolysis below
      0.2% and reduced platelet count and function. Binding of fibrin and platelets was
      higer on PET, inflammatory markers were lowest on Dyneema Purity UHMWPE. We
      concluded that the Hemobile minimally affects blood and could be adjusted to high
      blood flows, simulating arterial shear stress. The Hemobile was used to measure
      hemocompatibility of graft material and showed Dyneema Purity UHMWPE fiber in
      many ways more hemocompatible than ePTFE and PET.

PMID- 22649452
TI  - Comparative Genomic Analysis of Lactococcus garvieae Strains Isolated from
      Different Sources Reveals Candidate Virulence Genes.
AB  - Lactococcus garvieae is a major pathogen for fish. Two complete (ATCC 49156 and
      Lg2) and three draft (UNIUD074, 8831, and 21881) genome sequences of L. garvieae
      have recently been released. We here present the results of a comparative genomic
      analysis of these fish and human isolates of L. garvieae. The pangenome comprised
      1,542 core and 1,378 dispensable genes. The sequenced L. garvieae strains shared
      most of the possible virulence genes, but the capsule gene cluster was found only
      in fish-pathogenic strain Lg2. The absence of the capsule gene cluster in other
      nonpathogenic strains isolated from mastitis and vegetable was also confirmed by
      PCR. The fish and human isolates of L. garvieae contained the specific two and
      four adhesin genes, respectively, indicating that these adhesion proteins may be
      involved in the host specificity differences of L. garvieae. The discoveries
      revealed by the pangenomic analysis may provide significant insights into the
      biology of L. garvieae.

PMID- 22649451
TI  - Effects of substrate mechanics on contractility of cardiomyocytes generated from
      human pluripotent stem cells.
AB  - Human pluripotent stem cell (hPSC-) derived cardiomyocytes have potential
      applications in drug discovery, toxicity testing, developmental studies, and
      regenerative medicine. Before these cells can be reliably utilized,
      characterization of their functionality is required to establish their similarity
      to native cardiomyocytes. We tracked fluorescent beads embedded in 4.4-99.7 kPa
      polyacrylamide hydrogels beneath contracting neonatal rat cardiomyocytes and
      cardiomyocytes generated from hPSCs via growth-factor-induced directed
      differentiation to measure contractile output in response to changes in substrate
      mechanics. Contraction stress was determined using traction force microscopy, and
      morphology was characterized by immunocytochemistry for alpha-actinin and
      subsequent image analysis. We found that contraction stress of all types of
      cardiomyocytes increased with substrate stiffness. This effect was not linked to
      beating rate or morphology. We demonstrated that hPSC-derived cardiomyocyte
      contractility responded appropriately to isoprenaline and remained stable in
      culture over a period of 2 months. This study demonstrates that hPSC-derived
      cardiomyocytes have appropriate functional responses to substrate stiffness and
      to a pharmaceutical agent, which motivates their use in further applications such
      as drug evaluation and cardiac therapies.

PMID- 22649453
TI  - Evaluation and Clinical Validity of a New Questionnaire for Mikulicz's Disease.
AB  - Objectives. The characteristic features of Mikulicz's disease (MD) are diffuse
      enlargement of the lacrimal and submandibular glands, elevated levels of serum
      immunoglobulin (Ig)G4, and abundant infiltration of IgG4-positive plasmacytes
      into both glands. No disease index is available to properly evaluate MD, so we
      developed a functional assessment of MD, the Mikulicz's disease activity
      questionnaire (MAQ), and evaluated its clinical efficacy. Methods. We selected 18
      patients who were either being treated for MD or who had presented with
      recurrence. The patients completed a self-assessment and were scored according to
      the MAQ sheet during each visit between December 2009 and August 2011. Assessment
      items were in regard to increases or decreases in lacrimal and salivary gland
      enlargement and severity of sicca symptoms. Results. On the first visits, MAQ
      scores were high, but scores decreased rapidly as treatment progressed. When
      doses of glucocorticoid were reduced, some patients showed increased scores. Dry
      symptom scores increased initially. MAQ scores for patients with recurrent MD
      gradually increased over several months before relapse. However, some patients
      displayed no elevation in MAQ scores due to relapses at other sites. Conclusion.
      MAQ score can be used to quantify flares and treatment response and is useful for
      functional assessment of MD.

PMID- 22649454
TI  - Bipolar affective disorder and migraine.
AB  - This paper consists of a case history and an overview of the relationship,
      aetiology, and treatment of comorbid bipolar disorder migraine patients. A
      MEDLINE literature search was used. Terms for the search were bipolar disorder
      bipolar depression, mania, migraine, mood stabilizer. Bipolar disorder and
      migraine cooccur at a relatively high rate. Bipolar II patients seem to have a
      higher risk of comorbid migraine than bipolar I patients have. The literature on
      the common roots of migraine and bipolar disorder, including both genetic and
      neuropathological approaches, is broadly discussed. Moreover, bipolar disorder
      and migraine are often combined with a variety of other affective disorders, and,
      furthermore, behavioural factors also play a role in the origin and course of the
      diseases. Approach to treatment options is also difficult. Several papers point
      out possible remedies, for example, valproate, topiramate, which acts on both
      diseases, but no first-choice treatments have been agreed upon yet.

PMID- 22649455
TI  - Acute adrenal insufficiency associated with tuberculous vertebral osteomyelitis
      and lymphadenopathy: case report.
AB  - A 51-year-old man developed anorexia, dizziness, nausea, vomiting, and weight
      loss. He had orthostatic hypotension, hyponatremia, hyperkalemia, and
      hypocortisolemia, and the diagnosis of adrenal insufficiency was made. Magnetic
      resonance imaging (MRI) showed asymmetrically enlarged adrenal glands. Biopsy of
      a hypoechoic, enlarged, inguinal lymph node showed caseating granulomas. Lumbar
      MRI showed vertebral body height loss and abnormal signal in L1 and L2; vertebral
      biopsy showed chronic, necrotic, caseating granulomatous inflammation consistent
      with tuberculous osteomyelitis. Clinical improvement occurred with isoniazid,
      rifampicin, pyrazinamide, and corticosteroids. The differential diagnosis of
      adrenal insufficiency should include tuberculosis, especially in geographic
      regions where tuberculosis is endemic.

PMID- 22649456
TI  - Use of daptomycin for the treatment of methicillin-resistant coagulase-negative
      staphylococcal ventriculitis.
AB  - Coagulase-negative staphylococci (CoNS) are the main pathogens causing hospital
      acquired external-ventricular-drain- (EVD-) and lumbar-drain- (LD-) associated
      meningitis and ventriculitis. The treatment of these infections can be
      challenging and may require combination of intraventricular and intravenous
      administration of antibiotics. Limited animal data demonstrate rapid daptomycin
      bactericidal activity, adequate penetration in the setting of inflamed meninges,
      and extended half-life in the ventricles Steenbergen et al. (2009). There are
      limited clinical data using daptomycin intravenously and/or intraventricularly
      for the treatment of central nervous system infections (CNS) Elvy et al. (2008),
      Stucki et al. (2007), Lee et al. (2008) and Wallace et al. (2009). We report here
      our experience in the treatment of an EVD-related infection.

PMID- 22649457
TI  - Osseous Metaplasia in Castleman's Disease: A Case Report.
AB  - Background. Castleman's disease is a benign lymphoproliferative disorder. The
      disease may be localized or multicentric. Three histologic variants are
      recognized: hyaline vascular, plasma cell, and mixed types. Case. A 20-year-old
      man presented with large left axillary mass. The histologic examination of the
      resected mass showed follicular pattern with large nodules of mantle cells
      arranged concentrically around atrophic and vascularized germinal centers. There
      was also some benign-appearing bone trabeculae interspersed with lymphoid tissue.
      The diagnosis of Castleman's disease, hyaline-vascular type with osseous
      metaplasia, was made.

PMID- 22649458
TI  - Human immunodeficiency virus and leprosy coinfection: challenges in resource
      limited setups.
AB  - Mycobacteria leprae(leprosy) and HIV coinfection are rare in Kenya. This is
      likely related to the low prevalence (1 per 10,000 of population) of leprosy.
      Because leprosy is no longer a public health challenge there is generally a low
      index of suspicion amongst clinicians for its diagnosis. Management of a HIV-1
      leprosy-coinfected individual in a resource-constrained setting is challenging.
      Some of these challenges include difficulties in establishing a diagnosis of
      leprosy; the high pill burden of cotreatment with both antileprosy and
      antiretroviral drugs (ARVs); medications' side effects; drug interactions;
      scarcity of drug choices for both diseases. This challenge is more profound when
      managing a patient who requires second-line antiretroviral therapy (ART). We
      present an adult male patient coinfected with HIV and leprosy, who failed first
      line antiretroviral therapy (ART) and required second-line treatment. Due to
      limited choices in antileprosy drugs available, the patient received monthly
      rifampicin and daily lopinavir-/ritonavir-based antileprosy and ART regimens,
      respectively. Six months into his cotreatment, he seemed to have adequate
      virological control. This case report highlights the challenges of managing such
      a patient.

PMID- 22649459
TI  - Visceral leishmaniasis clinical management in endemic districts of India, Nepal,
      and bangladesh.
AB  - Background. National VL Elimination Programs in India, Nepal and Bangladesh face
      challenges as home-based Miltefosine treatment is introduced. Objectives. To
      study constraints of VL management in endemic districts within context of
      national elimination programs before and after intervention. Methods. Ninety-two
      and 41 newly diagnosed VL patients were interviewed for clinical and provider
      experience in 2009 before and in 2010 after intervention (district training and
      improved supply of diagnostics and drugs). Providers were assessed for adherence
      to treatment guidelines. Facilities and doctor-patient consultations were
      observed to assess quality of care. Results. Miltefosine use increased from 33%
      to 59% except in Nepal where amphotericin was better available. Incorrect dosage
      and treatment interruptions were rare. Advice on potential side effects was
      uncommon but improved significantly in 2010. Physicians did not rule out
      pregnancy prior to starting Miltefosine. Fever measurement or spleen palpation
      was infrequently done in Bangladesh but improved after intervention (from 23% to
      47%). Physician awareness of renal or liver toxicity as Miltefosine side effects
      was lower in Bangladesh. Bio-chemical monitoring was uncommon. Patient
      satisfaction with services remained low for ease of access or time provider spent
      with patient. Health facilities were better stocked with rK39 kits and
      Miltefosine in 2010.

PMID- 22649460
TI  - Moving "Forward" in Plasmodium Genetics through a Transposon-Based Approach.
AB  - The genome sequence of the human malaria parasite, Plasmodium falciparum, was
      released almost a decade ago. A majority of the Plasmodium genome, however,
      remains annotated to code for hypothetical proteins with unknown functions. The
      introduction of forward genetics has provided novel means to gain a better
      understanding of gene functions and their associated phenotypes in Plasmodium.
      Even with certain limitations, the technique has already shown significant
      promise to increase our understanding of parasite biology needed for rationalized
      drug and vaccine design. Further improvements to the mutagenesis technique and
      the design of novel genetic screens should lead us to some exciting discoveries
      about the critical weaknesses of Plasmodium, and greatly aid in the development
      of new disease intervention strategies.

PMID- 22649461
TI  - Excess early postnatal weight gain leads to increased abdominal fat in young
      children.
AB  - Background. Increased childhood weight gain has been associated with later
      adiposity. Whether excess early postnatal weight gain plays a role in childhood
      abdominal fat is unknown. Design. In the ongoing Wheezing Illnesses Study
      Leidsche Rijn (WHISTLER), birth cohort weight and length from birth to age 3
      months were obtained. In the first 316 five-year-olds, intra-abdominal and
      subcutaneous fat were measured ultrasonographically. Individual weight and length
      gain rates were assessed in each child. Internal Z-scores of weight for length
      gain (WLG) were calculated. Multiple imputation was used to deal with missing
      covariates. Results. Per-1-unit increase in Z-score WLG from birth to 3 months,
      BMI, waist circumference, and subcutaneous fat were significantly higher; 0.51
      kg/m(2), 0.84 cm, and 0.50 mm, respectively. After multiple imputation, a trend
      towards significance was observed for intra-abdominal fat as well (0.51 mm/SD).
      In the associations with 5-year adiposity, no interaction between postnatal Z
      score WLG and birth size was found. Conclusion. Excess early postnatal weight
      gain is associated with increased general and central adiposity, characterized by
      more subcutaneous and likely more intra-abdominal fat at 5 years of age.

PMID- 22649462
TI  - Intracellular Loop 2 Peptides of the Human 5HT1a Receptor are Differential
      Activators of Gi.
AB  - Peptide mimics of intracellular loop 2 (ic2) of the human 5HT1a receptor have
      been studied with respect to their ability to inhibit agonist binding via
      interference with receptor-G-protein coupling. These peptides give shallow
      concentration-effect relationships. Additionally, these peptides have been
      studied with respect to their ability to trigger the signal transduction system
      of this Gi-coupled receptor. Two signaling parameters have been quantified:
      concentration of intracellular cAMP and changes in incorporation into the G
      protein of a stable analog of GTP. In both cases, peptide mimics near midloop of
      ic2 actually show agonist activity with efficacy falling off toward both loop
      termini near TM 3 and TM 4. Previous results have suggested that the loop region
      near the TM3/ic2 interface is primarily responsible for receptor-G-protein
      coupling, while the current result emphasizes the mid-ic2 loop region's ability
      to activate the G protein following initial coupling. A limited number of
      peptides from the receptor's TM5/ic3 loop vicinity were also studied regarding
      agonist inhibition and G-protein activation. These peptides provide additional
      evidence that the human 5HT1a receptor, TM5/ic3 loop region, is involved in both
      coupling and activation actions. Overall, these results provide further
      information about potential pharmacological intervention and drug development
      with respect to the human 5HT1a receptor/G-protein system. Finally, the
      structural evidence generated here provides testable models pending
      crystallization and X-ray analysis of the receptor.

PMID- 22649463
TI  - The 2009 US federal cigarette tax increase and quitline utilization in 16 states.
AB  - BACKGROUND: On April 1, 2009, the federal cigarette excise tax increased from 39
      cents to $1.01 per pack. METHODS: This study describes call volumes to 16 state
      quitlines, characteristics of callers and cessation outcomes before and after the
      tax. RESULTS: Calls to the quitlines increased by 23.5% in 2009 and more whites,
      smokers >= 25 years of age, smokers of shorter duration, those with less
      education, and those who live with smokers called after (versus before) the tax.
      Quit rates at 7 months did not differ before versus after tax. CONCLUSIONS:
      Descriptive analyses revealed that the federal excise tax on cigarettes was
      associated with increased calls to quitlines but multivariate analyses revealed
      no difference in quit rates. However, more callers at the same quit rate
      indicates an increase in total number of successful quitters. If revenue obtained
      from increased taxation on cigarettes is put into cessation treatment, then it is
      likely future excise taxes would have an even greater effect.

PMID- 22649464
TI  - Adult current smoking: differences in definitions and prevalence estimates--NHIS
      and NSDUH, 2008.
AB  - OBJECTIVES: To compare prevalence estimates and assess issues related to the
      measurement of adult cigarette smoking in the National Health Interview Survey
      (NHIS) and the National Survey on Drug Use and Health (NSDUH). METHODS: 2008 data
      on current cigarette smoking and current daily cigarette smoking among adults
      >=18 years were compared. The standard NHIS current smoking definition, which
      screens for lifetime smoking >=100 cigarettes, was used. For NSDUH, both the
      standard current smoking definition, which does not screen, and a modified
      definition applying the NHIS current smoking definition (i.e., with screen) were
      used. RESULTS: NSDUH consistently yielded higher current cigarette smoking
      estimates than NHIS and lower daily smoking estimates. However, with use of the
      modified NSDUH current smoking definition, a notable number of subpopulation
      estimates became comparable between surveys. Younger adults and racial/ethnic
      minorities were most impacted by the lifetime smoking screen, with Hispanics
      being the most sensitive to differences in smoking variable definitions among all
      subgroups. CONCLUSIONS: Differences in current cigarette smoking definitions
      appear to have a greater impact on smoking estimates in some sub-populations than
      others. Survey mode differences may also limit intersurvey comparisons and trend
      analyses. Investigators are cautioned to use data most appropriate for their
      specific research questions.

PMID- 22649465
TI  - Prediction and identification of potential immunodominant epitopes in
      glycoproteins B, C, E, G, and I of herpes simplex virus type 2.
AB  - Twenty B candidate epitopes of glycoproteins B (gB2), C (gC2), E (gE2), G (gG2),
      and I (gI2) of herpes simplex virus type 2 (HSV-2) were predicted using DNAstar,
      Biosun, and Antheprot methods combined with the polynomial method. Subsequently,
      the biological functions of the peptides were tested via experiments in vitro.
      Among the 20 epitope peptides, 17 could react with the antisera to the
      corresponding parent proteins in the EIA tests. In particular, five peptides,
      namely, gB2(466-473) (EQDRKPRN), gC2(216-223) (GRTDRPSA), gE2(483-491)
      (DPPERPDSP), gG2(572-579) (EPPDDDDS), and gI2(286-295) (CRRRYRRPRG) had strong
      reaction with the antisera. All conjugates of the five peptides with the carrier
      protein BSA could stimulate mice into producing antibodies. The antisera to these
      peptides reacted strongly with the corresponding parent glycoproteins during the
      Western Blot tests, and the peptides reacted strongly with the antibodies against
      the parent glycoproteins during the EIA tests. The antisera against the five
      peptides could neutralize HSV-2 infection in vitro, which has not been reported
      until now. These results suggest that the immunodominant epitopes screened using
      software algorithms may be used for virus diagnosis and vaccine design against
      HSV-2.

PMID- 22649467
TI  - Evaluation of clinical and ultrasonographic parameters in psoriatic arthritis
      patients treated with adalimumab: a retrospective study.
AB  - OBJECTIVES: The aim of this study was to evaluate clinical and US-PD parameters
      in PsA during adalimumab treatment. METHODS: A retrospective study has been
      conducted in forty patients affected by moderate-to-severe peripheral PsA.
      Clinical, laboratory, and US-PD evaluations were performed at baseline, after 4,
      12, and 24 weeks of treatment. They included erythrocyte sedimentation rate
      (ESR), C-reactive protein (CRP), visual analogue scale (VAS), Health Assessment
      Questionnaire (HAQ) modified for Spondyloarthritis, Psoriasis Area Severity Index
      (PASI) score, the 28-joint Disease Activity Score (DAS 28), and US-PD assessment.
      US-PD findings were scored according to a semiquantitative scale (ranging 0-3)
      for synovial proliferation (SP), joint effusion (SE), bone erosions (BE), and PD.
      RESULTS: Data obtained for clinical, laboratory findings and US-PD evaluation
      showed statistical significant improvement in all the measures performed except
      for BE. A significant parallel decrease in SE, SP, and PD values were
      demonstrated. CONCLUSION: This study demonstrated that US-PD is a valid technique
      in monitoring the response to adalimumab in moderate-to-severe PsA.

PMID- 22649468
TI  - Increased frequency of circulating follicular helper T cells in patients with
      rheumatoid arthritis.
AB  - Follicular helper T (Tfh) cells are recognized as a distinct CD4(+) helper T-cell
      subset, which provides for B-cell activation and production of specific antibody
      responses, and play a critical role in the development of autoimmune disease. So
      far, only one study investigated the circulating Tfh cells increased in a subset
      of SLE patients. Since relatively little is known about the Tfh cells in
      rheumatoid arthritis (RA) patients, in this study, Tfh-cell frequency, related
      cytokine IL-21, and transcription factor Bcl-6 were investigated in 53 patients
      with RA and 31 health controls. Firstly, we found that the frequency of
      CD4(+)CXCR5(+)ICOS(high) Tfh cells was increased significantly in the peripheral
      blood of RA patients, compared with that in healthy controls. It is known that
      Tfh cells are critical for directing the development of an antibody response by
      germinal centers B cells; secondly, we observed that the Tfh-cell frequency is
      accompanied by the level of anti-CCP antibody in RA patients. Furthermore,
      expression of Bcl-6 mRNA and plasma IL-21 concentrations in RA patients was
      increased. Taken together, these findings have shown that the increased frequency
      of circulating Tfh cells is correlated with elevated levels of anti-CCP antibody,
      indicating the possible involvement of Tfh cells in the disease progression of
      RA.

PMID- 22649469
TI  - Developing policy for integrating biomedicine and traditional chinese medical
      practice using focus groups and the delphi technique.
AB  - In Hong Kong, statutory regulation for traditional Chinese medicine (TCM)
      practitioners has been implemented in the past decade. Increasing use of TCM on
      top of biomedicine (BM) services by the population has been followed; but
      corresponding policy development to integrate their practices has not yet been
      discussed. Using focus group methodology, we explore policy ideas for integration
      by collating views from frontline BM (n = 50) and TCM clinicians (n = 50).
      Qualitative data were analyzed under the guidance of structuration model of
      collaboration, a theoretical model for understanding interprofessional
      collaboration. From focus group findings we generated 28 possible approaches, and
      subsequently their acceptability was assessed by a two round Delphi survey
      amongst BM and TCM policy stakeholders (n = 12). Consensus was reached only on 13
      statements. Stakeholders agreed that clinicians from both paradigms should share
      common goals of providing patient-centered care, promoting the development of
      protocols for shared care and information exchange, as well as strengthening
      interprofessional connectivity and leadership for integration. On the other hand,
      attitudes amongst policy stakeholders were split on the possibility of fostering
      trust and mutual learning, as well as on enhancing innovation and governmental
      support. Future policy initiatives should focus on these controversial areas.

PMID- 22649470
TI  - Hepatoprotective Effects of Panus giganteus (Berk.) Corner against Thioacetamide-
      (TAA-) Induced Liver Injury in Rats.
AB  - Panus giganteus, a culinary and medicinal mushroom consumed by selected
      indigenous communities in Malaysia, is currently being considered for large scale
      cultivation. This study was undertaken to investigate the hepatoprotective
      effects of P. giganteus against thioacetamide- (TAA-) induced liver injury in
      Sprague-Dawley rats. The rats were injected intraperitoneally with TAA thrice
      weekly and were orally administered freeze-dried fruiting bodies of P. giganteus
      (0.5 or 1 g/kg) daily for two months, while control rats were given vehicle or P.
      giganteus only. After 60 days, rats administered with P. giganteus showed lower
      liver body weight ratio, restored levels of serum liver biomarkers and oxidative
      stress parameters comparable to treatment with the standard drug silymarin. Gross
      necropsy and histopathological examination further confirmed the hepatoprotective
      effects of P. giganteus. This is the first report on hepatoprotective effects of
      P. giganteus. The present study showed that P. giganteus was able to prevent or
      reduce the severity of TAA-induced liver injury.

PMID- 22649471
TI  - Protective Role of Phyllanthus niruri Extract against Thioacetamide-Induced Liver
      Cirrhosis in Rat Model.
AB  - A preclinical study was performed to determine if the extract from Phyllanthus
      niruri (PN) plays a protective role against liver cirrhosis induced by
      thioacetamide (TAA) in rats. Initially, acute toxicity was tested and the results
      showed that the extract was benign when applied to healthy rats. Next, the
      therapeutic effect of the extract was investigated using five groups of rats:
      control, TAA, silymarin, and PN high dose and low dose groups. Significant
      differences were observed between the TAA group and the other groups regarding
      body and liver weights, liver biochemical parameters, total antioxidant capacity,
      lipid peroxidation, and oxidative stress enzyme levels. Gross visualization
      indicated coarse granules on the surface of the hepatotoxic rats' livers, in
      contrast to the smoother surface in the livers of the silymarin and PN-treated
      rats. Histopathological analysis revealed necrosis, lymphocytes infiltration in
      the centrilobular region, and fibrous connective tissue proliferation in the
      livers of the hepatotoxic rats. But, the livers of the treated rats had
      comparatively minimal inflammation and normal lobular architecture. Silymarin and
      PN treatments effectively restored these measurements closer to their normal
      levels. Progression of liver cirrhosis induced by TAA in rats can be intervened
      using the PN extract and these effects are comparable to those of silymarin.

PMID- 22649466
TI  - Novel strategies for immunotherapy in multiple myeloma: previous experience and
      future directions.
AB  - Multiple myeloma (MM) is a life-threatening haematological malignancy for which
      standard therapy is inadequate. Autologous stem cell transplantation is a
      relatively effective treatment, but residual malignant sites may cause relapse.
      Allogeneic transplantation may result in durable responses due to antitumour
      immunity mediated by donor lymphocytes. However, morbidity and mortality related
      to graft-versus-host disease remain a challenge. Recent advances in understanding
      the interaction between the immune system of the patient and the malignant cells
      are influencing the design of clinically more efficient study protocols for MM.
      Cellular immunotherapy using specific antigen-presenting cells (APCs), to
      overcome aspects of immune incompetence in MM patients, has received great
      attention, and numerous clinical trials have evaluated the potential for
      dendritic cell (DC) vaccines as a novel immunotherapeutic approach. This paper
      will summarize the data investigating aspects of immunity concerning MM,
      immunotherapy for patients with MM, and strategies, on the way, to target the
      plasma cell more selectively. We also include the MM antigens and their specific
      antibodies that are of potential use for MM humoral immunotherapy, because they
      have demonstrated the most promising preclinical results.

PMID- 22649473
TI  - Protective Effects of Corni Fructus against Advanced Glycation Endproducts and
      Radical Scavenging.
AB  - We investigated the inhibition of advanced glycation endproduct (AGE) activity
      using the fluorescence characteristics of fractions and compounds from Corni
      Fructus. Corni Fructus extract and its iridoid glycoside components showed low
      inhibitory activities as well as the AGE inhibitor aminoguanidine. However, a low
      molecular weight polyphenol, 7-O-galloyl-D-sedoheptulose, and an antioxidant,
      trolox, showed high inhibitory activities compared with aminoguanidine under
      reactive conditions. The AGE-inhibiting activity of polyphenolic fractions of
      Corni Fructus ranged from a level comparable to Corni Fructus extract to the
      higher level of 7-O-galloyl-D-sedoheptulose. As well as the results of AGE
      inhibiting activity, Corni Fructus extract and iridoid components showed low or
      no 1,1-diphenyl-2-pycrylhydrazyl (DPPH) radical-scavenging activities, whereas 7
      O-galloyl-D-sedoheptulose showed a level comparable to trolox. Polyphenolic
      fractions of Corni Fructus quenched DPPH radicals in a concentration-dependent
      manner. Some fractions exerted a higher DPPH radical-scavenging activity compared
      with trolox and 7-O-galloyl-D-sedoheptulose. The DPPH radical-scavenging activity
      was significantly correlated with the AGE-inhibiting activity. These results
      suggest that polyphenolic fractions of Corni Fructus inhibited AGE formation by
      antioxidant activity including free radical scavenging. The strong DPPH radical
      scavenging and AGE-inhibiting fractions included ellagitannins and polymeric
      proanthocyanidins.

PMID- 22649472
TI  - Inhibition of NO(2), PGE(2), TNF-alpha, and iNOS EXpression by Shorea robusta L.:
      An Ethnomedicine Used for Anti-Inflammatory and Analgesic Activity.
AB  - This paper is an attempt to evaluate the anti-inflammatory and analgesic
      activities and the possible mechanism of action of tender leaf extracts of Shorea
      robusta, traditionally used in ailments related to inflammation. The acetic-acid
      induced writhing and tail flick tests were carried out for analgesic activity,
      while the anti-inflammatory activity was evaluated in carrageenan-and dextran-
      induced paw edema and cotton-pellet-induced granuloma model. The acetic-acid
      induced vascular permeability, erythrocyte membrane stabilization, release of
      proinflammatory mediators (nitric oxide and prostaglandin E(2)), and cytokines
      (tumor necrosis factor-alpha, and interleukins-1beta and -6) from
      lipopolysaccharide-stimulated human monocytic cell lines were assessed to
      understand the mechanism of action. The results revealed that both aqueous and
      methanol extract (400 mg/kg) caused significant reduction of writhing and tail
      flick, paw edema, granuloma tissue formation (P < 0.01), vascular permeability,
      and membrane stabilization. Interestingly, the aqueous extract at 40 MUg/mL
      significantly inhibited the production of NO and release of PGE(2), TNF-alpha, IL
      1beta, and IL-6. Chemically the extract contains flavonoids and triterpenes and
      toxicity study showed that the extract is safe. Thus, our study validated the
      scientific rationale of ethnomedicinal use of S. robusta and unveils its
      mechanism of action. However, chronic toxicological studies with active
      constituents are needed before its use.

PMID- 22649474
TI  - Anticancer Activity of Certain Herbs and Spices on the Cervical Epithelial
      Carcinoma (HeLa) Cell Line.
AB  - Acetone extracts of selected plant species were evaluated for their in vitro
      cytotoxicity against a noncancerous African green monkey kidney (Vero) cell line
      and an adenocarcinoma cervical cancer (HeLa) cell line. The plants studied were
      Origanum vulgare L. (Oregano), Rosmarinus officinalis L. (Upright and ground cove
      rosemary), Lavandula spica L. (Lavender), Laurus nobilis L. (Bay leaf), Thymus
      vulgaris L. (Thyme), Lavandula x intermedia L. (Margaret Roberts Lavender),
      Petroselinum crispum Mill. (Curly leaved parsley), Foeniculum vulgare Mill.
      (Fennel), and Capsicum annuum L. (Paprika). Antioxidant activity was determined
      using a quantitative DPPH (1,1-diphenyl-2-picryl hydrazyl) assay. The rosemary
      species exhibited effective radical scavenging capacity with 50% inhibitory
      concentration (IC(50)) of 3.48 +/- 0.218 MUg/mL and 10.84 +/- 0.125 MUg/mL and
      vitamin C equivalents of 0.351 g and 1.09 g for McConnell's Blue and Tuscan Blue,
      respectively. Cytotoxicity was measured using XTT (Sodium 3'-[1-(phenyl amino
      carbonyl)-3,4-tetrazolium]-bis-[4-methoxy-6-nitro] benzene sulfonic acid hydrate)
      colorimetric assay. Only L. nobilis and O. vulgare exhibited pronounced effects
      on the HeLa cell line. Dose-dependent studies revealed IC(50) of 34.46 +/- 0.48
      MUg/mL and 126.3 +/- 1.00 MUg/mL on the HeLa cells and on the Vero cells 124.1
      MUg/mL +/- 18.26 and 163.8 MUg/mL +/- 2.95 for L. nobilis and O. vulgare,
      respectively. Light (eosin and haematoxylin staining) and confocal microscopy
      (Hoechst 33342, acridine orange, and propidium iodide staining) were used to
      evaluate the cytotoxic mechanism of action for L. nobilis and O. vulgare.

PMID- 22649475
TI  - Effect of auricular acupressure on peri- and early postmenopausal women with
      anxiety: a double-blinded, randomized, and controlled pilot study.
AB  - We tested effects of auricular acupressure on peri- and early postmenopausal
      women with anxiety (PPWA). Fifty PPWA were randomly assigned to the auricular
      acupressure group (AG) or the sham group (SG). After 3 meals and before sleep
      every day for 4 weeks, the AG received auricular acupressure on the bilateral ear
      shenmen and subcortex points for 3 min per point on alternating ears. The SG
      received sham auricular acupressure. The Alprazolam was reduced from 0.5 mg/day
      at baseline to 0.3 mg/day 4 weeks after auricular acupressure (4 W) in the AG (P
      < .05) whereas maintained at 0.5 mg/day in the SG (P > .05). The Zolpidem was
      reduced from 3.0 mg/day at baseline to 1.5 mg/day at 4 W (P < .05) whereas was
      reduced from 2.4 mg/day to 1.9 mg/day at 4 W in the SG (P > .05), thus,
      significant tapering medication, suggesting auricular acupressure is helpful to
      PPWA.

PMID- 22649476
TI  - Effectiveness of a tai-chi training and detraining on functional capacity,
      symptomatology and psychological outcomes in women with fibromyalgia.
AB  - Background. The purpose was to analyze the effects of Tai-Chi training in women
      with fibromyalgia (FM). Methods. Thirty-two women with FM (mean age, 51.4 +/- 6.8
      years) attended to Tai-Chi intervention 3 sessions weekly for 28 weeks. The
      outcome measures were: tenderness, body composition, functional capacity and
      psychological outcomes (Fibromyalgia impact questionnaire (FIQ), Short Form
      Health Survey 36 (SF-36)). Results. Patients showed improvements on pain
      threshold, total number of tender points and algometer score (all P < 0.001). The
      intervention was effective on 6-min walk (P = 0.006), back scratch (P = 0.002),
      handgrip strength (P = 0.006), chair stand, chair sit & reach, 8 feet up & go and
      blind flamingo tests (all P < 0.001). Tai-Chi group improved the FIQ total score
      (P < 0.001) and six subscales: stiffness (P = 0.005), pain, fatigue, morning
      tiredness, anxiety, and depression (all P < 0.001). The intervention was also
      effective in six SF-36 subscales: bodily pain (P = 0.003), vitality (P = 0.018),
      physical functioning, physical role, general health, and mental health (all P <
      0.001). Conclusions. A 28-week Tai-Chi intervention showed improvements on pain,
      functional capacity, symptomatology and psychological outcomes in female FM
      patients.

PMID- 22649478
TI  - Emodin, a Naturally Occurring Anthraquinone Derivative, Ameliorates Dyslipidemia
      by Activating AMP-Activated Protein Kinase in High-Fat-Diet-Fed Rats.
AB  - The aim of this study was to investigate the antiobesity and antihyperlipidaemic
      effects of emodin on high-fat diet (HFD)-induced obese rats, and on the
      regulation of the expression of the genes involved in lipid metabolism to
      elucidate the mechanisms. After being fed HFD for two weeks, Wistar rats were
      dosed orally with emodin (40 and 80 mg kg(-1)) or pioglitazone (20 mg kg(-1)),
      once daily for eight weeks. Emodin (80 mg kg(-1) per day) displayed similar
      characteristics to pioglitazone (20 mg kg(-1) per day) in reducing body weight
      gain, plasma lipid levels as well as coronary artery risk index and atherogenic
      index of HFD-fed rats. Emodin also caused dose related reductions in the hepatic
      triglyceride and cholesterol contents and lowered hepatic lipid droplets
      accumulation in HFD-fed rats. Emodin and pioglitazone enhanced the
      phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream
      targeting enzyme, acetyl-CoA carboxylase, up-regulated gene expression of
      carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element
      binding protein 1 and fatty acid synthase protein levels in hepatocytes of HFD
      fed rats. Our findings suggest emodin could attenuate lipid accumulation by
      decreasing lipogenesis and increasing mitochondrial fatty acid beta-oxidation
      mediated by activation of the AMPK signaling pathway.

PMID- 22649477
TI  - Electroacupuncture Attenuates Ovalbumin-Induced Allergic Asthma via Modulating
      CD4(+)CD25(+) Regulatory T Cells.
AB  - A mouse pulmonary hypersensitivity experimental model that mimics human asthma
      was developed, and electroacupuncture (EA) treatment was shown to reduce allergic
      inflammatory processes. In addition, we also assessed whether the beneficial
      effects of EA on allergic asthma could be correlated with CD4(+)CD25(+)Foxp3(+)
      regulatory T cells (Treg). Cellular profiles and histopathologic analysis
      demonstrated that peribronchial and perivascular inflammatory cell infiltrates
      were significantly decreased in the EA-treated groups when compared to the OVA
      and anti-CD25 Ab-injected (Treg depletion) groups. Furthermore, total BAL cells
      were reduced in the EA groups when compared to other groups. Interestingly, the
      population of CD4(+)CD25(+)Foxp3(+)Tregs in pneumonocytes increased in EA-treated
      group when compared to OVA and Treg depletion groups. These results imply that EA
      stimulation at ST 36 may affect CD4(+)CD25(+)Foxp3(+) Treg in an OVA-induced
      experimental model and may enhance Treg function by suppressing other T cells and
      limiting the immune response.

PMID- 22649480
TI  - Computational models of neuron-astrocyte interactions lead to improved efficacy
      in the performance of neural networks.
AB  - The importance of astrocytes, one part of the glial system, for information
      processing in the brain has recently been demonstrated. Regarding information
      processing in multilayer connectionist systems, it has been shown that systems
      which include artificial neurons and astrocytes (Artificial Neuron-Glia Networks)
      have well-known advantages over identical systems including only artificial
      neurons. Since the actual impact of astrocytes in neural network function is
      unknown, we have investigated, using computational models, different astrocyte
      neuron interactions for information processing; different neuron-glia algorithms
      have been implemented for training and validation of multilayer Artificial Neuron
      Glia Networks oriented toward classification problem resolution. The results of
      the tests performed suggest that all the algorithms modelling astrocyte-induced
      synaptic potentiation improved artificial neural network performance, but their
      efficacy depended on the complexity of the problem.

PMID- 22649479
TI  - The effects of jiang-zhi-ning and its main components on cholesterol metabolism.
AB  - To examine how Jiang-Zhi-Ning (JZN) regulates cholesterol metabolism and compare
      the role of its four main components. We established a beagle model of
      hyperlipidemia, fed with JZN extract and collected JZN-containing serum 0, 1, 2,
      4, and 6 h later. Human liver cells Bel-7402 were stimulated with 10% JZN
      containing serum as well as the four main components of JZN and Atorvastatin. The
      mRNA expression of LDL receptor (LDL-R), 3-hydroxy-3-methyl-glutaryl-CoA
      reductase (HMG-CoAR), cytochrome P450 7A1 (CYP7A1), and acetyl-Coenzyme A
      acetyltransferase 2 (ACAT2) was measured by real-time PCR. LDL-R surface
      expression and LDL-binding and internalization were examined by flow cytometry.
      The results showed that JZN-containing serum significantly increased the mRNA
      expression of LDL-R, HMG-CoAR, and CYP7A1 in Bel-7402 cells. All the four
      components significantly increased the mRNA and protein expression of LDL-R and
      HMG-CoAR and decreased the mRNA and protein expression of ACAT2 in Bel-7402
      cells. Hyperinand chrysophanol also markedly increased the mRNA expression of
      CYP7A1. Stimulation with stilbene glycosidesignificantly increased the surface
      expression of LDL-R and the binding and internalization of LDL. In conclusion,
      JZN and its four components have close relationship with the process of
      cholesterol metabolism, emphasizing their promising application as new drug
      candidates in the treatment of hyperlipidemia.

PMID- 22649481
TI  - Implication of crystal water molecules in inhibitor binding at ALR2 active site.
AB  - Water molecules play a crucial role in mediating the interaction between a ligand
      and a macromolecule. The solvent environment around such biomolecule controls
      their structure and plays important role in protein-ligand interactions. An
      understanding of the nature and role of these water molecules in the active site
      of a protein could greatly increase the efficiency of rational drug design
      approaches. We have performed the comparative crystal structure analysis of
      aldose reductase to understand the role of crystal water in protein-ligand
      interaction. Molecular dynamics simulation has shown the versatile nature of
      water molecules in bridge H bonding during interaction. Occupancy and life time
      of water molecules depend on the type of cocrystallized ligand present in the
      structure. The information may be useful in rational approach to customize the
      ligand, and thereby longer occupancy and life time for bridge H-bonding.

PMID- 22649482
TI  - Statistical analysis of single-trial Granger causality spectra.
AB  - Granger causality analysis is becoming central for the analysis of interactions
      between neural populations and oscillatory networks. However, it is currently
      unclear whether single-trial estimates of Granger causality spectra can be used
      reliably to assess directional influence. We addressed this issue by combining
      single-trial Granger causality spectra with statistical inference based on
      general linear models. The approach was assessed on synthetic and
      neurophysiological data. Synthetic bivariate data was generated using two
      autoregressive processes with unidirectional coupling. We simulated two
      hypothetical experimental conditions: the first mimicked a constant and
      unidirectional coupling, whereas the second modelled a linear increase in
      coupling across trials. The statistical analysis of single-trial Granger
      causality spectra, based on t-tests and linear regression, successfully recovered
      the underlying pattern of directional influence. In addition, we characterised
      the minimum number of trials and coupling strengths required for significant
      detection of directionality. Finally, we demonstrated the relevance for
      neurophysiology by analysing two local field potentials (LFPs) simultaneously
      recorded from the prefrontal and premotor cortices of a macaque monkey performing
      a conditional visuomotor task. Our results suggest that the combination of single
      trial Granger causality spectra and statistical inference provides a valuable
      tool for the analysis of large-scale cortical networks and brain connectivity.

PMID- 22649483
TI  - The time required to estimate the case fatality ratio of influenza using only the
      tip of an iceberg: joint estimation of the virulence and the transmission
      potential.
AB  - Estimating the case fatality ratio (CFR) of a novel strain of influenza virus
      during the early stage of the pandemic is one of key epidemiological tasks to be
      conducted as rapid research response. Past experience during the epidemics of
      severe acute respiratory syndrome (SARS) and influenza A (H1N1-2009) posed
      several technical challenges in estimating the CFR in real time. The present
      study aimed to develop a simple method to estimate the CFR based on readily
      available datasets, that is, confirmed cases and deaths, while addressing some of
      the known technical issues. To assess the reliability and validity of the
      proposed method, we examined the minimum length of time required for the assigned
      CFR to be included within the 95% confidence intervals and for the estimated CFR
      to be below a prespecified cut-off value by means of Monte Carlo simulations.
      Overall, the smaller the transmission potential was, the longer it took to
      compare the estimated CFR against the cut-off value. If policymaking and public
      health response have to be made based on the CFR estimate derived from the
      proposed method and readily available data, it should be noted that the
      successful estimation may take longer than a few months.

PMID- 22649484
TI  - Verbs in the lexicon: Why is hitting easier than breaking?
AB  - Adult speakers use verbs in syntactically appropriate ways. For example, they
      know implicitly that the boy hit at the fence is acceptable but the boy broke at
      the fence is not. We suggest that this knowledge is lexically encoded in semantic
      decompositions. The decomposition for break verbs (e.g. crack, smash) is
      hypothesized to be more complex than that for hit verbs (e.g. kick, kiss).
      Specifically, the decomposition of a break verb denotes that "an entity changes
      state as the result of some external force" whereas the decomposition for a hit
      verb denotes only that "an entity potentially comes in contact with another
      entity." In this article, verbs of the two types were compared in a lexical
      decision experiment - Experiment 1 - and they were compared in sentence
      comprehension experiments with transitive sentences (e.g. the car hit the bicycle
      and the car broke the bicycle) - Experiments 2 and 3. In Experiment 1, processing
      times were shorter for the hit than the break verbs and in Experiments 2 and 3,
      processing times were shorter for the hit sentences than the break sentences,
      results that are in accord with the complexities of the postulated semantic
      decompositions.

PMID- 22649485
TI  - Multi-patterned dynamics of mitochondrial fission and fusion in a living cell.
AB  - Mitochondria are highly-dynamic organelles, but it is challenging to monitor
      quantitatively their dynamics in a living cell. Here we developed a novel
      approach to determine the global occurrence of mitochondrial fission and fusion
      events in living human epithelial cells (Hela) and mouse embryonic fibroblast
      cells (MEF). Distinct patterns of sequential events including fusion followed by
      fission (Fu-Fi), the so-called "kiss and run" model previously described, fission
      followed by fusion (Fi-Fu), fusion followed by fusion (Fu-Fu), and fission
      followed by fission (Fi-Fi) were observed concurrently. The paired events
      appeared in high frequencies with short lifetimes and large sizes of individual
      mitochondria, as compared to those for unpaired events. The high frequencies of
      paired events were found to be biologically significant. The presence of membrane
      uncoupler CCCP enhanced the frequency of paired events (from both Fu-Fi and Fi-Fu
      patterns) with a reduced mitochondrial size. Knock-out of mitofusin protein Mfn1
      increased the frequency of fission with increased lifetime of unpaired events
      whereas deletion of both Mfn1 and Mfn2 resulted in an instable dynamics. These
      results indicated that the paired events were dominant but unpaired events were
      not negligible, which provided a new insight into mitochondrial dynamics. In
      addition to kiss and run model of action, our data suggest that, from a global
      visualization over an entire cell, multiple patterns of action appeared in
      mitochondrial fusion and fission.

PMID- 22649486
TI  - Spatially explicit burden estimates of malaria in Tanzania: bayesian
      geostatistical modeling of the malaria indicator survey data.
AB  - A national HIV/AIDS and malaria parasitological survey was carried out in
      Tanzania in 2007-2008. In this study the parasitological data were analyzed: i)
      to identify climatic/environmental, socio-economic and interventions factors
      associated with child malaria risk and ii) to produce a contemporary, high
      spatial resolution parasitaemia risk map of the country. Bayesian geostatistical
      models were fitted to assess the association between parasitaemia risk and its
      determinants. bayesian kriging was employed to predict malaria risk at unsampled
      locations across Tanzania and to obtain the uncertainty associated with the
      predictions. Markov chain Monte Carlo (MCMC) simulation methods were employed for
      model fit and prediction. Parasitaemia risk estimates were linked to population
      data and the number of infected children at province level was calculated. Model
      validation indicated a high predictive ability of the geostatistical model, with
      60.00% of the test locations within the 95% credible interval. The results
      indicate that older children are significantly more likely to test positive for
      malaria compared with younger children and living in urban areas and better-off
      households reduces the risk of infection. However, none of the environmental and
      climatic proxies or the intervention measures were significantly associated with
      the risk of parasitaemia. Low levels of malaria prevalence were estimated for
      Zanzibar island. The population-adjusted prevalence ranges from 0.29% in
      Kaskazini province (Zanzibar island) to 18.65% in Mtwara region. The pattern of
      predicted malaria risk is similar with the previous maps based on historical
      data, although the estimates are lower. The predicted maps could be used by
      decision-makers to allocate resources and target interventions in the regions
      with highest burden of malaria in order to reduce the disease transmission in the
      country.

PMID- 22649487
TI  - Effect of chromosomal instability on the mutation-selection balance in
      unicellular populations.
AB  - This paper develops a mathematical model describing the evolutionary dynamics of
      a unicellular, asexually replicating population exhibiting chromosomal
      instability. Chromosomal instability is a form of genetic instability
      characterized by the gain or loss of entire chromosomes during cell division. We
      assume that the cellular genome is divided into several homologous groups of
      chromosomes, and that a single functional chromosome per homologous group is
      required for the cell to have the wild-type fitness. If the fitness is unaffected
      by the total number of chromosomes in the cell, our model is analytically
      solvable, and yields a mean fitness at mutation-selection balance that is
      identical to the mean fitness when there is no chromosomal instability. If this
      assumption is relaxed and the total number of chromosomes in the cell is not
      allowed to increase without bound, then chromosomal instability leads to a
      reduction in mean fitness. The results of this paper provide a useful baseline
      that can inform both future theoretial and experimental studies of chromosomal
      instability.

PMID- 22649488
TI  - Inclusion and human rights in health policies: comparative and benchmarking
      analysis of 51 policies from Malawi, Sudan, South Africa and Namibia.
AB  - While many health services strive to be equitable, accessible and inclusive,
      peoples' right to health often goes unrealized, particularly among vulnerable
      groups. The extent to which health policies explicitly seek to achieve such goals
      sets the policy context in which services are delivered and evaluated. An
      analytical framework was developed--EquiFrame--to evaluate 1) the extent to which
      21 Core Concepts of human rights were addressed in policy documents, and 2)
      coverage of 12 Vulnerable Groups who might benefit from such policies. Using this
      framework, analysis of 51 policies across Malawi, Namibia, South Africa and
      Sudan, confirmed the relevance of all Core Concepts and Vulnerable Groups.
      Further, our analysis highlighted some very strong policies, serious shortcomings
      in others as well as country-specific patterns. If social inclusion and human
      rights do not underpin policy formation, it is unlikely they will be inculcated
      in service delivery. EquiFrame facilitates policy analysis and benchmarking, and
      provides a means for evaluating policy revision and development.

PMID- 22649489
TI  - Generic delivery of payload of nanoparticles intracellularly via hybrid polymer
      capsules for bioimaging applications.
AB  - Towards the goal of development of a generic nanomaterial delivery system and
      delivery of the 'as prepared' nanoparticles without 'further surface
      modification' in a generic way, we have fabricated a hybrid polymer capsule as a
      delivery vehicle in which nanoparticles are loaded within their cavity. To this
      end, a generic approach to prepare nanomaterials-loaded polyelectrolyte
      multilayered (PEM) capsules has been reported, where polystyrene sulfonate
      (PSS)/polyallylamine hydrochloride (PAH) polymer capsules were employed as
      nano/microreactors to synthesize variety of nanomaterials (metal nanoparticles;
      lanthanide doped inorganic nanoparticles; gadolinium based nanoparticles, cadmium
      based nanoparticles; different shapes of nanoparticles; co-loading of two types
      of nanoparticles) in their hollow cavity. These nanoparticles-loaded capsules
      were employed to demonstrate generic delivery of payload of nanoparticles
      intracellularly (HeLa cells), without the need of individual nanoparticle surface
      modification. Validation of intracellular internalization of nanoparticles-loaded
      capsules by HeLa cells was ascertained by confocal laser scanning microscopy. The
      green emission from Tb(3+) was observed after internalization of
      LaF(3):Tb(3+)(5%) nanoparticles-loaded capsules by HeLa cells, which suggests
      that nanoparticles in hybrid capsules retain their functionality within the
      cells. In vitro cytotoxicity studies of these nanoparticles-loaded capsules
      showed less/no cytotoxicity in comparison to blank capsules or untreated cells,
      thus offering a way of evading direct contact of nanoparticles with cells because
      of the presence of biocompatible polymeric shell of capsules. The proposed hybrid
      delivery system can be potentially developed to avoid a series of biological
      barriers and deliver multiple cargoes (both simultaneous and individual delivery)
      without the need of individual cargo design/modification.

PMID- 22649491
TI  - Low levels of human HIP14 are sufficient to rescue neuropathological,
      behavioural, and enzymatic defects due to loss of murine HIP14 in Hip14-/- mice.
AB  - Huntingtin Interacting Protein 14 (HIP14) is a palmitoyl acyl transferase (PAT)
      that was first identified due to altered interaction with mutant huntingtin, the
      protein responsible for Huntington Disease (HD). HIP14 palmitoylates a specific
      set of neuronal substrates critical at the synapse, and downregulation of HIP14
      by siRNA in vitro results in increased cell death in neurons. We previously
      reported that mice lacking murine Hip14 (Hip14-/-) share features of HD. In the
      current study, we have generated human HIP14 BAC transgenic mice and crossed them
      to the Hip14-/- model in order to confirm that the defects seen in Hip14-/- mice
      are in fact due to loss of Hip14. In addition, we sought to determine whether
      human HIP14 can provide functional compensation for loss of murine Hip14. We
      demonstrate that despite a relative low level of expression, as assessed via
      Western blot, BAC-derived human HIP14 compensates for deficits in neuropathology,
      behavior, and PAT enzyme function seen in the Hip14-/- model. Our findings yield
      important insights into HIP14 function in vivo.

PMID- 22649490
TI  - Medium chain fatty acids are selective peroxisome proliferator activated receptor
      (PPAR) gamma activators and pan-PPAR partial agonists.
AB  - Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor
      (PPAR) gamma to increase insulin sensitivity in type 2 diabetes (T2DM), but
      deleterious effects of these ligands mean that selective modulators with improved
      clinical profiles are needed. We obtained a crystal structure of PPARgamma ligand
      binding domain (LBD) and found that the ligand binding pocket (LBP) is occupied
      by bacterial medium chain fatty acids (MCFAs). We verified that MCFAs (C8-C10)
      bind the PPARgamma LBD in vitro and showed that they are low-potency partial
      agonists that display assay-specific actions relative to TZDs; they act as very
      weak partial agonists in transfections with PPARgamma LBD, stronger partial
      agonists with full length PPARgamma and exhibit full blockade of PPARgamma
      phosphorylation by cyclin-dependent kinase 5 (cdk5), linked to reversal of
      adipose tissue insulin resistance. MCFAs that bind PPARgamma also antagonize TZD
      dependent adipogenesis in vitro. X-ray structure B-factor analysis and molecular
      dynamics (MD) simulations suggest that MCFAs weakly stabilize C-terminal
      activation helix (H) 12 relative to TZDs and this effect is highly dependent on
      chain length. By contrast, MCFAs preferentially stabilize the H2-H3/beta-sheet
      region and the helix (H) 11-H12 loop relative to TZDs and we propose that MCFA
      assay-specific actions are linked to their unique binding mode and suggest that
      it may be possible to identify selective PPARgamma modulators with useful
      clinical profiles among natural products.

PMID- 22649492
TI  - The Goldilocks effect: human infants allocate attention to visual sequences that
      are neither too simple nor too complex.
AB  - Human infants, like immature members of any species, must be highly selective in
      sampling information from their environment to learn efficiently. Failure to be
      selective would waste precious computational resources on material that is
      already known (too simple) or unknowable (too complex). In two experiments with 7
      and 8-month-olds, we measure infants' visual attention to sequences of events
      varying in complexity, as determined by an ideal learner model. Infants'
      probability of looking away was greatest on stimulus items whose complexity
      (negative log probability) according to the model was either very low or very
      high. These results suggest a principle of infant attention that may have broad
      applicability: infants implicitly seek to maintain intermediate rates of
      information absorption and avoid wasting cognitive resources on overly simple or
      overly complex events.

PMID- 22649493
TI  - Influence of HLA-DRB1 and HLA-DQB1 alleles on IgG antibody response to the P.
      vivax MSP-1, MSP-3alpha and MSP-9 in individuals from Brazilian endemic area.
AB  - BACKGROUND: The antibody response generated during malaria infections is of
      particular interest, since the production of specific IgG antibodies is required
      for acquisition of clinical immunity. However, variations in antibody responses
      could result from genetic polymorphism of the HLA class II genes. Given the
      increasing focus on the development of subunit vaccines, studies of the influence
      of class II alleles on the immune response in ethnically diverse populations is
      important, prior to the implementation of vaccine trials. METHODS AND FINDINGS:
      In this study, we evaluated the influence of HLA-DRB1* and -DQB1* allelic groups
      on the naturally acquired humoral response from Brazilian Amazon individuals (n =
      276) against P. vivax Merozoite Surface Protein-1 (MSP-1), MSP-3alpha and MSP-9
      recombinant proteins. Our results provide information concerning these three P.
      vivax antigens, relevant for their role as immunogenic surface proteins and
      vaccine candidates. Firstly, the studied population was heterogeneous presenting
      13 HLA-DRB1* and 5 DQB1* allelic groups with a higher frequency of HLA-DRB1*04
      and HLA-DQB1*03. The proteins studied were broadly immunogenic in a naturally
      exposed population with high frequency of IgG antibodies against PvMSP1-19
      (86.7%), PvMSP-3 (77%) and PvMSP-9 (76%). Moreover, HLA-DRB1*04 and HLA-DQB1*03
      alleles were associated with a higher frequency of IgG immune responses against
      five out of nine antigens tested, while HLA-DRB1*01 was associated with a high
      frequency of non-responders to repetitive regions of PvMSP-9, and the DRB1*16
      allelic group with the low frequency of responders to PvMSP3 full length
      recombinant protein. CONCLUSIONS: HLA-DRB1*04 alleles were associated with high
      frequency of antibody responses to five out of nine recombinant proteins tested
      in Rondonia State, Brazil. These features could increase the success rate of
      future clinical trials based on these vaccine candidates.

PMID- 22649494
TI  - A limited role for suppression in the central field of individuals with
      strabismic amblyopia.
AB  - BACKGROUND: Although their eyes are pointing in different directions, people with
      long-standing strabismic amblyopia typically do not experience double-vision or
      indeed any visual symptoms arising from their condition. It is generally believed
      that the phenomenon of suppression plays a major role in dealing with the
      consequences of amblyopia and strabismus, by preventing images from the
      weaker/deviating eye from reaching conscious awareness. Suppression is thus a
      highly sophisticated coping mechanism. Although suppression has been studied for
      over 100 years the literature is equivocal in relation to the extent of the
      retina that is suppressed, though the method used to investigate suppression is
      crucial to the outcome. There is growing evidence that some measurement methods
      lead to artefactual claims that suppression exists when it does not.
      METHODOLOGY/RESULTS: Here we present the results of an experiment conducted with
      a new method to examine the prevalence, depth and extent of suppression in ten
      individuals with strabismic amblyopia. Seven subjects (70%) showed no evidence
      whatsoever for suppression and in the three individuals who did (30%), the depth
      and extent of suppression was small. CONCLUSIONS: Suppression may play a much
      smaller role in dealing with the negative consequences of strabismic amblyopia
      than previously thought. Whereas recent claims of this nature have been made only
      in those with micro-strabismus our results show extremely limited evidence for
      suppression across the central visual field in strabismic amblyopes more
      generally. Instead of suppressing the image from the weaker/deviating eye, we
      suggest the visual system of individuals with strabismic amblyopia may act to
      maximise the possibilities for binocular co-operation. This is consistent with
      recent evidence from strabismic and amblyopic individuals that their binocular
      mechanisms are intact, and that, just as in visual normals, performance with two
      eyes is better than with the better eye alone in these individuals.

PMID- 22649495
TI  - Is a genome a codeword of an error-correcting code?
AB  - Since a genome is a discrete sequence, the elements of which belong to a set of
      four letters, the question as to whether or not there is an error-correcting code
      underlying DNA sequences is unavoidable. The most common approach to answering
      this question is to propose a methodology to verify the existence of such a code.
      However, none of the methodologies proposed so far, although quite clever, has
      achieved that goal. In a recent work, we showed that DNA sequences can be
      identified as codewords in a class of cyclic error-correcting codes known as
      Hamming codes. In this paper, we show that a complete intron-exon gene, and even
      a plasmid genome, can be identified as a Hamming code codeword as well. Although
      this does not constitute a definitive proof that there is an error-correcting
      code underlying DNA sequences, it is the first evidence in this direction.

PMID- 22649496
TI  - Race and the fragility of the legal distinction between juveniles and adults.
AB  - Legal precedent establishes juvenile offenders as inherently less culpable than
      adult offenders and thus protects juveniles from the most severe of punishments.
      But how fragile might these protections be? In the present study, simply bringing
      to mind a Black (vs. White) juvenile offender led participants to view juveniles
      in general as significantly more similar to adults in their inherent culpability
      and to express more support for severe sentencing. Indeed, these differences in
      participants' perceptions of this foundational legal precedent distinguishing
      between juveniles and adults accounted for their greater support for severe
      punishment. These results highlight the fragility of protections for juveniles
      when race is in play. Furthermore, we suggest that this fragility may have broad
      implications for how juveniles are seen and treated in the criminal justice
      system.

PMID- 22649497
TI  - Long-term health outcomes in children born to mothers with diabetes: a population
      based cohort study.
AB  - BACKGROUND: To examine whether prenatal exposure to parental type 1 diabetes,
      type 2 diabetes, or gestational diabetes is associated with an increased risk of
      malignant neoplasm or diseases of the circulatory system in the offspring.
      METHODS/PRINCIPAL FINDINGS: We conducted a population-based cohort study of
      1,781,576 singletons born in Denmark from 1977 to 2008. Children were followed
      for up to 30 years from the day of birth until the onset of the outcomes under
      study, death, emigration, or December 31, 2009, whichever came first. We used Cox
      proportional hazards model to estimate hazard ratios (HR) with 95% confidence
      intervals (95% CI) for the outcomes under study while adjusting for potential
      confounders. An increased risk of malignant neoplasm was found in children
      prenatally exposed to maternal type 2 diabetes (HR = 2.2, 95%CI: 1.5-3.2). An
      increased risk of diseases of the circulatory system was found in children
      exposed to maternal type 1 diabetes (HR = 2.2, 95%CI: 1.6-3.0), type 2 diabetes
      (HR = 1.4, 95%CI: 1.1-1.7), and gestational diabetes (HR = 1.3, 95%CI: 1.1-1.6),
      but results were attenuated after excluding children with congenital
      malformations. An increased risk of diseases of the circulatory system was also
      found in children exposed to paternal type 2 diabetes (HR = 1.5, 95%CI: 1.1-2.2)
      and the elevated risk remained after excluding children with congenital
      malformations. CONCLUSIONS: This study suggests that susceptibility to malignant
      neoplasm is modified partly by fetal programming. Diseases of the circulatory
      system may be modified by genetic factors, other time-stable family factors, or
      fetal programming.

PMID- 22649498
TI  - Back to basics: pitting edema and the optimization of hypertension treatment in
      incident peritoneal dialysis patients (BRAZPD).
AB  - Systemic arterial hypertension is an important risk factor for cardiovascular
      disease that is frequently observed in populations with declining renal function.
      Initiation of renal replacement therapy at least partially decreases signs of
      fluid overload; however, high blood pressure levels persist in the majority of
      patients after dialysis initiation. Hypervolemia due to water retention
      predisposes peritoneal dialysis (PD) patients to hypertension and can clinically
      manifest in several forms, including peripheral edema. The approaches to detect
      edema, which include methods such as bioimpedance, inferior vena cava diameter
      and biomarkers, are not always available to physicians worldwide. For clinical
      examinations, the presence of pitting located in the lower extremities and/or
      over the sacrum to diagnose the presence of peripheral edema in their patients
      are frequently utulized. We evaluated the impact of edema on the control of blood
      pressure of incident PD patients during the first year of dialysis treatment.
      Patients were recruited from 114 Brazilian dialysis centers that were
      participating in the BRAZPD study for a total of 1089 incident patients.
      Peripheral edema was diagnosed by the presence of pitting after finger pressure
      was applied to the edematous area. Patients were divided into 2 groups: those
      with and without edema according to the monthly medical evaluation. Blood
      arterial pressure, body mass index, the number of antihypertensive drugs and
      comorbidities were analyzed. We observed an initial BP reduction in the first
      five months and a stabilization of blood pressure levels from five to twelve
      months. The edematous group exhibited higher blood pressure levels than the group
      without edema during the follow-up. The results strongly indicate that the
      presence of a simple and easily detectable clinical sign of peripheral edema is a
      very relevant tool that could be used to re-evaluate not only the patient's
      clinical hypertensive status but also the PD prescription and patient compliance.

PMID- 22649499
TI  - Ontogeny of Toll-like and NOD-like receptor-mediated innate immune responses in
      Papua New Guinean infants.
AB  - Studies addressing the ontogeny of the innate immune system in early life have
      reported mainly on Toll-like receptor (TLR) responses in infants living in high
      income countries, with little or even no information on other pattern recognition
      receptors or on early life innate immune responses in children living under very
      different environmental conditions in less-developed parts of the world. In this
      study, we describe whole blood innate immune responses to both Toll-like and
      nucleotide-binding oligomerization domain (NOD)-like receptor agonists including
      the widely used vaccine adjuvant 'alum' in a group of Papua New Guinean infants
      aged 1-3 (n = 18), 4-6 (n = 18), 7-12 (n = 21) and 13-18 (n = 10) months old.
      Depending on the ligands and cytokines studied, different age-related patterns
      were found: alum-induced IL-1beta and CXCL8 responses were found to significantly
      decline with increasing age; inflammatory (IL-6, IL-1beta, IFN-gamma) responses
      to TLR2 and TLR3 agonists increased; and IL-10 responses remained constant or
      increased during infancy, while TNF-alpha responses either declined or remained
      the same. We report for the first time that whole blood innate immune responses
      to the vaccine adjuvant alum decrease with age in infancy; a finding that may
      imply that the adjuvant effect of alum in pediatric vaccines could be age
      related. Our findings further suggest that patterns of innate immune development
      may vary between geographically diverse populations, which in line with the
      'hygiene hypothesis' particularly involves persistence of innate IL-10 responses
      in populations experiencing higher infectious pressure.

PMID- 22649500
TI  - Sound frequency and aural selectivity in sound-contingent visual motion
      aftereffect.
AB  - BACKGROUND: One possible strategy to evaluate whether signals in different
      modalities originate from a common external event or object is to form
      associations between inputs from different senses. This strategy would be quite
      effective because signals in different modalities from a common external event
      would then be aligned spatially and temporally. Indeed, it has been demonstrated
      that after adaptation to visual apparent motion paired with alternating auditory
      tones, the tones begin to trigger illusory motion perception to a static visual
      stimulus, where the perceived direction of visual lateral motion depends on the
      order in which the tones are replayed. The mechanisms underlying this phenomenon
      remain unclear. One important approach to understanding the mechanisms is to
      examine whether the effect has some selectivity in auditory processing. However,
      it has not yet been determined whether this aftereffect can be transferred across
      sound frequencies and between ears. METHODOLOGY/PRINCIPAL FINDINGS: Two circles
      placed side by side were presented in alternation, producing apparent motion
      perception, and each onset was accompanied by a tone burst of a specific and
      unique frequency. After exposure to this visual apparent motion with tones for a
      few minutes, the tones became drivers for illusory motion perception. However,
      the aftereffect was observed only when the adapter and test tones were presented
      at the same frequency and to the same ear. CONCLUSIONS/SIGNIFICANCE: These
      findings suggest that the auditory processing underlying the establishment of
      novel audiovisual associations is selective, potentially but not necessarily
      indicating that this processing occurs at an early stage.

PMID- 22649501
TI  - Common variants in MAGI2 gene are associated with increased risk for cognitive
      impairment in schizophrenic patients.
AB  - Schizophrenia is a complex psychiatric disorder characterized by positive
      symptoms, negative symptoms, and cognitive impairment. MAGI2, a relatively large
      gene (~1.5 Mbps) that maps to chromosome 7q21, is involved in recruitment of
      neurotransmitter receptors such as AMPA- and NMDA-type glutamate receptors. A
      genetic association study designed to evaluate the association between MAGI2 and
      cognitive performance or schizophrenia has not been conducted. In this case
      control study, we examined the relationship of single nucleotide polymorphism
      (SNP) variations in MAGI2 and risk for schizophrenia in a large Japanese sample
      and explored the potential relationships between variations in MAGI2 and aspects
      of human cognitive function related to glutamate activity. Based on the result of
      first schizophrenia genome-wide association study in a Japanese population
      (JGWAS), we selected four independent SNPs and performed an association study
      using a large independent Japanese sample set (cases 1624, controls 1621).
      Wisconsin Card Sorting Test (WCST) was used to evaluate executive function in 114
      cases and 91 controls. We found suggestive evidence for genetic association of
      common SNPs within MAGI2 locus and schizophrenia in Japanese population.
      Furthermore in terms of association between MAGI2 and cognitive performance, we
      observed that genotype effect of rs2190665 on WCST score was significant (p =
      0.034) and rs4729938 trended toward significance (p = 0.08). In conclusion,
      although we could not detect strong genetic evidence for association of common
      variants in MAGI2 and increased schizophrenia risk in a Japanese population,
      these SNPs may increase risk of cognitive impairment in schizophrenic patients.

PMID- 22649502
TI  - New species in the Old World: Europe as a frontier in biodiversity exploration, a
      test bed for 21st century taxonomy.
AB  - The number of described species on the planet is about 1.9 million, with ca.
      17,000 new species described annually, mostly from the tropics. However, taxonomy
      is usually described as a science in crisis, lacking manpower and funding, a
      politically acknowledged problem known as the Taxonomic Impediment. Using data
      from the Fauna Europaea database and the Zoological Record, we show that contrary
      to general belief, developed and heavily-studied parts of the world are important
      reservoirs of unknown species. In Europe, new species of multicellular
      terrestrial and freshwater animals are being discovered and named at an
      unprecedented rate: since the 1950s, more than 770 new species are on average
      described each year from Europe, which add to the 125,000 terrestrial and
      freshwater multicellular species already known in this region. There is no sign
      of having reached a plateau that would allow for the assessment of the magnitude
      of European biodiversity. More remarkably, over 60% of these new species are
      described by non-professional taxonomists. Amateurs are recognized as an
      essential part of the workforce in ecology and astronomy, but the magnitude of
      non-professional taxonomist contributions to alpha-taxonomy has not been fully
      realized until now. Our results stress the importance of developing a system that
      better supports and guides this formidable workforce, as we seek to overcome the
      Taxonomic Impediment and speed up the process of describing the planetary
      biodiversity before it is too late.

PMID- 22649504
TI  - The general age of leadership: older-looking presidential candidates win
      elections during war.
AB  - As nation-state leaders age they increasingly engage in inter-state militarized
      disputes yet in industrialized societies a steady decrease in testosterone
      associated with aging is observed--which suggests a decrease in dominance
      behavior. The current paper points out that from modern societies to Old World
      monkeys increasing both in age and social status encourages dominant strategies
      to maintain acquired rank. Moreover, it is argued this consistency has shaped an
      implicit prototype causing followers to associate older age with dominance
      leadership. It is shown that (i) faces of older leaders are preferred during
      intergroup conflict and (ii) morphing U.S. Presidential candidates to appear
      older or younger has an overriding effect on actual election outcomes. This
      indicates that democratic voting can be systematically adjusted by activating
      innate biases. These findings appear to create a new line of research regarding
      the biology of leadership and contextual cues of age.

PMID- 22649503
TI  - Suppression of AP1 transcription factor function in keratinocyte suppresses
      differentiation.
AB  - Our previous study shows that inhibiting activator protein one (AP1)
      transcription factor function in murine epidermis, using dominant-negative c-jun
      (TAM67), increases cell proliferation and delays differentiation. To understand
      the mechanism of action, we compare TAM67 impact in mouse epidermis and in
      cultured normal human keratinocytes. We show that TAM67 localizes in the nucleus
      where it forms TAM67 homodimers that competitively interact with AP1
      transcription factor DNA binding sites to reduce endogenous jun and fos factor
      binding. Involucrin is a marker of keratinocyte differentiation that is expressed
      in the suprabasal epidermis and this expression requires AP1 factor interaction
      at the AP1-5 site in the promoter. TAM67 interacts competitively at this site to
      reduce involucrin expression. TAM67 also reduces endogenous c-jun, junB and junD
      mRNA and protein level. Studies with c-jun promoter suggest that this is due to
      reduced transcription of the c-jun gene. We propose that TAM67 suppresses
      keratinocyte differentiation by interfering with endogenous AP1 factor binding to
      regulator elements in differentiation-associated target genes, and by reducing
      endogenous c-jun factor expression.

PMID- 22649505
TI  - A thermophilic ionic liquid-tolerant cellulase cocktail for the production of
      cellulosic biofuels.
AB  - Generation of biofuels from sugars in lignocellulosic biomass is a promising
      alternative to liquid fossil fuels, but efficient and inexpensive bioprocessing
      configurations must be developed to make this technology commercially viable. One
      of the major barriers to commercialization is the recalcitrance of plant cell
      wall polysaccharides to enzymatic hydrolysis. Biomass pretreatment with ionic
      liquids (ILs) enables efficient saccharification of biomass, but residual ILs
      inhibit both saccharification and microbial fuel production, requiring extensive
      washing after IL pretreatment. Pretreatment itself can also produce biomass
      derived inhibitory compounds that reduce microbial fuel production. Therefore,
      there are multiple points in the process from biomass to biofuel production that
      must be interrogated and optimized to maximize fuel production. Here, we report
      the development of an IL-tolerant cellulase cocktail by combining thermophilic
      bacterial glycoside hydrolases produced by a mixed consortia with recombinant
      glycoside hydrolases. This enzymatic cocktail saccharifies IL-pretreated biomass
      at higher temperatures and in the presence of much higher IL concentrations than
      commercial fungal cocktails. Sugars obtained from saccharification of IL
      pretreated switchgrass using this cocktail can be converted into biodiesel (fatty
      acid ethyl-esters or FAEEs) by a metabolically engineered strain of E. coli.
      During these studies, we found that this biodiesel-producing E. coli strain was
      sensitive to ILs and inhibitors released by saccharification. This cocktail will
      enable the development of novel biomass to biofuel bioprocessing configurations
      that may overcome some of the barriers to production of inexpensive cellulosic
      biofuels.

PMID- 22649506
TI  - Paired tumor and normal whole genome sequencing of metastatic olfactory
      neuroblastoma.
AB  - BACKGROUND: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal tract
      with little molecular characterization. We performed whole genome sequencing
      (WGS) on paired normal and tumor DNA from a patient with metastatic-ONB to
      identify the somatic alterations that might be drivers of tumorigenesis and/or
      metastatic progression. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA was isolated
      from fresh frozen tissue from a metastatic lesion and whole blood, followed by
      WGS at >30X depth, alignment and mapping, and mutation analyses. Sanger
      sequencing was used to confirm selected mutations. Sixty-two somatic short
      nucleotide variants (SNVs) and five deletions were identified inside coding
      regions, each causing a non-synonymous DNA sequence change. We selected seven
      SNVs and validated them by Sanger sequencing. In the metastatic ONB samples
      collected several months prior to WGS, all seven mutations were present. However,
      in the original surgical resection specimen (prior to evidence of metastatic
      disease), mutations in KDR, MYC, SIN3B, and NLRC4 genes were not present,
      suggesting that these were acquired with disease progression and/or as a result
      of post-treatment effects. CONCLUSIONS/SIGNIFICANCE: This work provides insight
      into the evolution of ONB cancer cells and provides a window into the more
      complex factors, including tumor clonality and multiple driver mutations.

PMID- 22649507
TI  - Mutations in an AP2 transcription factor-like gene affect internode length and
      leaf shape in maize.
AB  - BACKGROUND: Plant height is an important agronomic trait that affects yield and
      tolerance to certain abiotic stresses. Understanding the genetic control of plant
      height is important for elucidating the regulation of maize development and has
      practical implications for trait improvement in plant breeding.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, two independent, semi-dwarf maize
      EMS mutants, referred to as dwarf & irregular leaf (dil1), were isolated and
      confirmed to be allelic. In comparison to wild type plants, the mutant plants
      have shorter internodes, shorter, wider and wrinkled leaves, as well as smaller
      leaf angles. Cytological analysis indicated that the leaf epidermal cells and
      internode parenchyma cells are irregular in shape and are arranged in a more
      random fashion, and the mutants have disrupted leaf epidermal patterning. In
      addition, parenchyma cells in the dil1 mutants are significantly smaller than
      those in wild-type plants. The dil1 mutation was mapped on the long arm of
      chromosome 6 and a candidate gene, annotated as an AP2 transcription factor-like,
      was identified through positional cloning. Point mutations near exon-intron
      junctions were identified in both dil1 alleles, resulting in mis-spliced
      variants. CONCLUSION: An AP2 transcription factor-like gene involved in stalk and
      leaf development in maize has been identified. Mutations near exon-intron
      junctions of the AP2 gene give mis-spliced transcript variants, which result in
      shorter internodes and wrinkled leaves.

PMID- 22649508
TI  - The beneficial effects of antifreeze proteins in the vitrification of immature
      mouse oocytes.
AB  - Antifreeze proteins (AFPs) are a class of polypeptides that permit organismal
      survival in sub-freezing environments. The purpose of this study was to
      investigate the effect of AFP supplementation on immature mouse oocyte
      vitrification. Germinal vesicle-stage oocytes were vitrified using a two-step
      exposure to equilibrium and vitrification solution in the presence or absence of
      500 ng/mL of AFP III. After warming, oocyte survival, in vitro maturation,
      fertilization, and embryonic development up to the blastocyst stage were
      assessed. Spindle and chromosome morphology, membrane integrity, and the
      expression levels of several genes were assessed in in vitro matured oocytes. The
      rate of blastocyst formation was significantly higher and the number of caspase
      positive blastomeres was significantly lower in the AFP-treated group compared
      with the untreated group. The proportion of oocytes with intact
      spindles/chromosomes and stable membranes was also significantly higher in the
      AFP group. The AFP group showed increased Mad2, Hook-1, Zar1, Zp1, and Bcl2
      expression and lower Eg5, Zp2, Caspase6, and Rbm3 expression compared with the
      untreated group. Supplementation of the vitrification medium with AFP has a
      protective effect on immature mouse oocytes, promoting their resistance to
      chilling injury. AFPs may preserve spindle forming ability and membrane integrity
      at GV stage. The fertilization and subsequent developmental competence of oocytes
      may be associated with the modulation of Zar1, Zp1/Zp2, Bcl2, Caspase6, and Rbm3.

PMID- 22649509
TI  - IL28B genetic variation is associated with spontaneous clearance of hepatitis C
      virus, treatment response, serum IL-28B levels in Chinese population.
AB  - BACKGROUND: The interleukin-28B gene (IL28B) locus has been associated with host
      resistance to hepatitis C virus (HCV) infection and response to PEG-IFN/RBV
      treatment in western populations. This study was to determine whether this gene
      variant is also associated with spontaneous clearance of HCV infection, treatment
      response and IL-28B protein production in Chinese patients. METHODS: We genotyped
      IL28B genetic variations (rs12980275, rs8103142, rs8099917 and rs12979860) by
      pyrosequencing DNA samples from cohorts consisting of 529 subjects with
      persistent HCV infection, 196 subjects who cleared the infection, 171 healthy
      individuals and 235 chronic HCV patients underwent IFN/RBV treatment. The
      expression of IL-28B were measured by ELISA and RT-PCR. RESULTS: We found that
      the four IL28B variants were in complete linkage disequilibrium (r2 = 0.97-0.98).
      The rs12979860 CC genotype was strongly associated with spontaneously HCV
      clearance and successful IFN/RBV treatment compared to the CT/TT. IL-28B levels
      in persistent HCV patients were significantly lower than subjects who
      spontaneously resolved HCV and healthy controls and were also associated with
      high levels of ALT (alanine aminotransferase) and AST (aspartate
      aminotransferase). IL-28B levels were also significantly lower in individuals
      carrying T alleles than CC homozygous. CONCLUSIONS: Thus, the rs12979860-CC
      variant upstream of IL28B gene is associated with spontaneous clearance of HCV,
      susceptible to IFN/RBV treatment and increased IL-28B levels in this Chinese
      population.

PMID- 22649510
TI  - Signature movements lead to efficient search for threatening actions.
AB  - The ability to find and evade fighting persons in a crowd is potentially life
      saving. To investigate how the visual system processes threatening actions, we
      employed a visual search paradigm with threatening boxer targets among
      emotionally-neutral walker distractors, and vice versa. We found that a boxer
      popped out for both intact and scrambled actions, whereas walkers did not. A
      reverse correlation analysis revealed that observers' responses clustered around
      the time of the "punch", a signature movement of boxing actions, but not around
      specific movements of the walker. These findings support the existence of a
      detector for signature movements in action perception. This detector helps in
      rapidly detecting aggressive behavior in a crowd, potentially through an
      expedited (sub)cortical threat-detection mechanism.

PMID- 22649511
TI  - Recovery potential of a western lowland gorilla population following a major
      Ebola outbreak: results from a ten year study.
AB  - Investigating the recovery capacity of wildlife populations following demographic
      crashes is of great interest to ecologists and conservationists. Opportunities to
      study these aspects are rare due to the difficulty of monitoring populations both
      before and after a demographic crash. Ebola outbreaks in central Africa have
      killed up to 95% of the individuals in affected western lowland gorilla (Gorilla
      gorilla gorilla) populations. Assessing whether and how fast affected populations
      recover is essential for the conservation of this critically endangered taxon.
      The gorilla population visiting Lokoue forest clearing, Odzala-Kokoua National
      Park, Republic of the Congo, has been monitored before, two years after and six
      years after Ebola affected it in 2004. This allowed us to describe Ebola's short
      term and long-term impacts on the structure of the population. The size of the
      population, which included around 380 gorillas before the Ebola outbreak, dropped
      to less than 40 individuals after the outbreak. It then remained stable for six
      years after the outbreak. However, the demographic structure of this small
      population has significantly changed. Although several solitary males have
      disappeared, the immigration of adult females, the formation of new breeding
      groups, and several birth events suggest that the population is showing potential
      to recover. During the outbreak, surviving adult and subadult females joined old
      solitary silverbacks. Those females were subsequently observed joining young
      silverbacks, forming new breeding groups where they later gave birth.
      Interestingly, some females were observed joining silverbacks that were unlikely
      to have sired their infant, but no infanticide was observed. The consequences of
      the Ebola outbreak on the population structure were different two years and six
      years after the outbreak. Therefore, our results could be used as demographic
      indicators to detect and date outbreaks that have happened in other, non
      monitored gorilla populations.

PMID- 22649512
TI  - No evidence for a trade-off between reproductive investment and immunity in a
      rodent.
AB  - Life history theory assumes there are trade-offs between competing functions such
      as reproduction and immunity. Although well studied in birds, studies of the
      trade-offs between reproduction and immunity in small mammals are scarce. Here we
      examined whether reduced immunity is a consequence of reproductive effort in
      lactating Brandt's voles (Lasiopodomys brandtii). Specifically, we tested the
      effects of lactation on immune function (Experiment I). The results showed that
      food intake and resting metabolic rate (RMR) were higher in lactating voles (6<=
      litter size <=8) than that in non-reproductive voles. Contrary to our
      expectation, lactating voles also had higher levels of serum total Immunoglobulin
      G (IgG) and anti-keyhole limpet hemocyanin (KLH) IgG and no change in
      phytohemagglutinin (PHA) response and anti-KLH Immunoglobulin M (IgM) compared
      with non-reproductive voles, suggesting improved rather than reduced immune
      function. To further test the effect of differences in reproductive investment on
      immunity, we compared the responses between natural large (n>=8) and small litter
      size (n<=6) (Experiment II) and manipulated large (11-13) and small litter size
      (2-3) (Experiment III). During peak lactation, acquired immunity (PHA response,
      anti-KLH IgG and anti-KLH IgM) was not significantly different between voles
      raising large or small litters in both experiments, despite the measured
      difference in reproductive investment (greater litter size, litter mass, RMR and
      food intake in the voles raising larger litters). Total IgG was higher in voles
      with natural large litter size than those with natural small litter size, but
      decreased in the enlarged litter size group compared with control and reduced
      group. Our results showed that immune function is not suppressed to compensate
      the high energy demands during lactation in Brandt's voles and contrasting the
      situation in birds, is unlikely to be an important aspect mediating the trade-off
      between reproduction and survival.

PMID- 22649513
TI  - Selective attention to task-irrelevant emotional distractors is unaffected by the
      perceptual load associated with a foreground task.
AB  - A number of studies have shown that emotionally arousing stimuli are
      preferentially processed in the human brain. Whether or not this preference
      persists under increased perceptual load associated with a task at hand remains
      an open question. Here we manipulated two possible determinants of the
      attentional selection process, perceptual load associated with a foreground task
      and the emotional valence of concurrently presented task-irrelevant distractors.
      As a direct measure of sustained attentional resource allocation in early visual
      cortex we used steady-state visual evoked potentials (SSVEPs) elicited by
      distinct flicker frequencies of task and distractor stimuli. Subjects either
      performed a detection (low load) or discrimination (high load) task at a
      centrally presented symbol stream that flickered at 8.6 Hz while task-irrelevant
      neutral or unpleasant pictures from the International Affective Picture System
      (IAPS) flickered at a frequency of 12 Hz in the background of the stream. As
      reflected in target detection rates and SSVEP amplitudes to both task and
      distractor stimuli, unpleasant relative to neutral background pictures more
      strongly withdrew processing resources from the foreground task. Importantly,
      this finding was unaffected by the factor 'load' which turned out to be a weak
      modulator of attentional processing in human visual cortex.

PMID- 22649514
TI  - Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines
      against chloroquine-resistant parasites.
AB  - Chloroquine (CQ) is a cost effective antimalarial drug with a relatively good
      safety profile (or therapeutic index). However, CQ is no longer used alone to
      treat patients with Plasmodium falciparum due to the emergence and spread of CQ
      resistant strains, also reported for P. vivax. Despite CQ resistance, novel drug
      candidates based on the structure of CQ continue to be considered, as in the
      present work. One CQ analog was synthesized as monoquinoline (MAQ) and compared
      with a previously synthesized bisquinoline (BAQ), both tested against P.
      falciparum in vitro and against P. berghei in mice, then evaluated in vitro for
      their cytotoxicity and ability to inhibit hemozoin formation. Their interactions
      with residues present in the NADH binding site of P falciparum lactate
      dehydrogenase were evaluated using docking analysis software. Both compounds were
      active in the nanomolar range evaluated through the HRPII and hypoxanthine tests.
      MAQ and BAQ derivatives were not toxic, and both compounds significantly
      inhibited hemozoin formation, in a dose-dependent manner. MAQ had a higher
      selectivity index than BAQ and both compounds were weak PfLDH inhibitors, a
      result previously reported also for CQ. Taken together, the two CQ analogues
      represent promising molecules which seem to act in a crucial point for the
      parasite, inhibiting hemozoin formation.

PMID- 22649516
TI  - Structure of the afferent terminals in terminal ganglion of a cricket and
      persistent homology.
AB  - We use topological data analysis to investigate the three dimensional spatial
      structure of the locus of afferent neuron terminals in crickets Acheta
      domesticus. Each afferent neuron innervates a filiform hair positioned on a
      cercus: a protruding appendage at the rear of the animal. The hairs transduce air
      motion to the neuron signal that is used by a cricket to respond to the
      environment. We stratify the hairs (and the corresponding afferent terminals)
      into classes depending on hair length, along with position. Our analysis uncovers
      significant structure in the relative position of these terminal classes and
      suggests the functional relevance of this structure. Our method is very robust to
      the presence of significant experimental and developmental noise. It can be used
      to analyze a wide range of other point cloud data sets.

PMID- 22649515
TI  - Macrophage migration inhibitory factor antagonist blocks the development of
      endometriosis in vivo.
AB  - Endometriosis, a disease of reproductive age women, is a major cause of
      infertility, menstrual disorders and pelvic pain. Little is known about its
      etiopathology, but chronic pelvic inflammation is a common feature in affected
      women. Beside symptomatic treatment of endometriosis-associated pain, only two
      main suboptimal therapeutic approaches (hormonal and invasive surgery) are
      generally recommended to patients and no specific targeted treatment is
      available. Our studies led to the detection of a marked increase in the
      expression of macrophage migration inhibitory factor (MIF) in the eutopic
      endometrium, the peripheral blood and the peritoneal fluid of women with
      endometriosis, and in early, vascularized and active endometriotic lesions.
      Herein, we developed a treatment model of endometriosis, where human endometrial
      tissue was first allowed to implant into the peritoneal cavity of nude mice, to
      assess in vivo the effect of a specific antagonist of MIF (ISO-1) on the
      progression of endometriosis and evaluate its efficacy as a potential therapeutic
      tool. Administration of ISO-1 led to a significant decline of the number, size
      and in situ dissemination of endometriotic lesions. We further showed that ISO-1
      may act by significantly inhibiting cell adhesion, tissue remodeling,
      angiogenesis and inflammation as well as by altering the balance of pro- and anti
      apoptotic factors. Actually, mice treatment with ISO-1 significantly reduced the
      expression of cell adhesion receptors alphav and beta3 integrins (P<0.05), matrix
      metalloproteinases (MMP) 2 and 9 (P<0.05), vascular endothelial cell growth
      factor (VEGF) (P<0.01), interleukin 8 (IL8) (P<0.05), cyclooxygenease (COX)2
      (P<0.001) and the anti-apoptotic protein Bcl2 (P<0.01), but significantly induced
      the expression of Bax (P<0.05), a potent pro-apoptotic protein. These data
      provide evidence that specific inhibition of MIF alters endometriotic tissue
      growth and progression in vivo and may represent a promising potential
      therapeutic avenue.

PMID- 22649517
TI  - Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of
      myocardial infarction, diabetes, cancer and mortality. The Tromso Study.
AB  - OBJECTIVE: Low serum 25(OH)D levels are associated with cardiovascular risk
      factors, and also predict future myocardial infarction (MI), type 2 diabetes
      (T2DM), cancer and all-cause mortality. Recently several single nucleotide
      polymorphisms (SNPs) associated with serum 25-hydroxyvitamin D (25(OH)D) level
      have been identified. If these relations are causal one would expect a similar
      association between these SNPs and health. METHODS: DNA was prepared from
      subjects 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 as well as a
      randomly selected control group. The endpoint registers were complete up to 2007
      2010. Genotyping was performed for 17 SNPs related to the serum 25(OH)D level.
      RESULTS: A total of 9528 subjects were selected for genetic analyses which were
      successfully performed for at least one SNP in 9471 subjects. Among these, 2025
      were registered with MI, 1092 with T2DM, 2924 with cancer and 3828 had died. The
      mean differences in serum 25(OH)D levels between SNP genotypes with the lowest
      and highest serum 25(OH)D levels varied from 0.1 to 7.8 nmol/L. A genotype score
      based on weighted risk alleles regarding low serum 25(OH)D levels was
      established. There was no consistent association between the genotype score or
      individuals SNPs and MI, T2DM, cancer, mortality or risk factors for disease.
      However, for rs6013897 genotypes (located at the 24-hydroxylase gene (CYP24A1))
      there was a significant association with breast cancer (P<0.05). CONCLUSION: Our
      results do not support nor exclude a causal relationship between serum 25(OH)D
      levels and MI, T2DM, cancer or mortality, and our observation on breast cancer
      needs confirmation. Further genetic studies are warranted, particularly in
      populations with vitamin D deficiency. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01395303.

PMID- 22649518
TI  - M. tuberculosis induces potent activation of IDO-1, but this is not essential for
      the immunological control of infection.
AB  - Indoleamine 2,3-dioxygenesae-1 (IDO-1) catalyses the initial, rate-limiting step
      in tryptophan metabolism, thereby regulating tryptophan availability and the
      formation of downstream metabolites, including picolinic and quinolinic acid. We
      found that Mycobacterium tuberculosis infection induced marked upregulation of
      IDO-1 expression in both human and murine macrophages in vitro and in the lungs
      of mice following aerosol challenge with M. tuberculosis. The absence of IDO-1 in
      dendritic cells enhanced the activation of mycobacteria-specific T cells in
      vitro. Interestingly, IDO-1-deficiency during M. tuberculosis infection in mice
      was not associated with altered mycobacteria-specific T cell responses in vivo.
      The bacterial burden of infected organs, pulmonary inflammatory responses, and
      survival were also comparable in M. tuberculosis-infected IDO-1 deficient and
      wild type animals. Tryptophan is metabolised into either picolinic acid or
      quinolinic acid, but only picolinic acid inhibited the growth of M. tuberculosis
      in vitro. By contrast macrophages infected with pathogenic mycobacteria, produced
      quinolinic, rather than picolinic acid, which did not reduce M. tuberculosis
      growth in vitro. Therefore, although M. tuberculosis induces robust expression of
      IDO-1 and activation of tryptophan metabolism, IDO-1-deficiency fails to impact
      on the immune control and the outcome of the infection in the mouse model of
      tuberculosis.

PMID- 22649519
TI  - Analysis of the paired TCR alpha- and beta-chains of single human T cells.
AB  - Analysis of the paired i.e. matching TCR alpha- and beta-chain rearrangements of
      single human T cells is required for a precise investigation of clonal diversity,
      tissue distribution and specificity of protective and pathologic T-cell mediated
      immune responses. Here we describe a multiplex RT-PCR based technology, which for
      the first time allows for an unbiased analysis of the complete sequences of both
      alpha- and beta-chains of TCR from single T cells. We validated our technology by
      the analysis of the pathologic T-cell infiltrates from tissue lesions of two T
      cell mediated autoimmune diseases, psoriasis vulgaris (PV) and multiple sclerosis
      (MS). In both disorders we could detect various T cell clones as defined by
      multiple T cells with identical alpha- and beta-chain rearrangements distributed
      across the tissue lesions. In PV, single cell TCR analysis of lesional T cells
      identified clonal CD8(+) T cell expansions that predominated in the epidermis of
      psoriatic plaques. An MS brain lesion contained two dominant CD8(+) T-cell clones
      that extended over the white and grey matter and meninges. In both diseases
      several clonally expanded T cells carried dual TCRs composed of one Vbeta and two
      different Valpha-chain rearrangements. These results show that our technology is
      an efficient instrument to analyse alphabeta-T cell responses with single cell
      resolution in man. It should facilitate essential new insights into the
      mechanisms of protective and pathologic immunity in many human T-cell mediated
      conditions and allow for resurrecting functional TCRs from any alphabeta-T cell
      of choice that can be used for investigating their specificity.

PMID- 22649520
TI  - Assessing the Revised Child Anxiety and Depression Scale (RCADS) in a national
      sample of Danish youth aged 8-16 years.
AB  - Early identification of anxiety among youth is required to prevent them from
      going unrecognised and untreated by mental health professionals. A precise
      identification of the young person's primary difficulty is also required to guide
      treatment programs. Availability of a valid and easily administrable assessment
      tool is crucial for identifying youth suffering from anxiety disorders. The
      purpose of the present study was therefore to examine the psychometric properties
      of the Danish version of the Revised Children's Anxiety and Depression Scale
      (RCADS). A total of 667 youth from community schools (4(th) through 9(th) grade)
      across Denmark participated in the study. The psychometric properties of the
      RCADS-(DAN) resembled those reported in US and Europe. Within scale reliability
      was excellent with Chronbach's alpha of.96. All subscales also showed good to
      excellent internal reliability. The study provides convincing evidence that the
      RCADS-(DAN) is a valid assessment tool for screening anxiety in Danish youth.

PMID- 22649521
TI  - A predictive model of intein insertion site for use in the engineering of
      molecular switches.
AB  - Inteins are intervening protein domains with self-splicing ability that can be
      used as molecular switches to control activity of their host protein.
      Successfully engineering an intein into a host protein requires identifying an
      insertion site that permits intein insertion and splicing while allowing for
      proper folding of the mature protein post-splicing. By analyzing sequence and
      structure based properties of native intein insertion sites we have identified
      four features that showed significant correlation with the location of the intein
      insertion sites, and therefore may be useful in predicting insertion sites in
      other proteins that provide native-like intein function. Three of these
      properties, the distance to the active site and dimer interface site, the SVM
      score of the splice site cassette, and the sequence conservation of the site
      showed statistically significant correlation and strong predictive power, with
      area under the curve (AUC) values of 0.79, 0.76, and 0.73 respectively, while the
      distance to secondary structure/loop junction showed significance but with less
      predictive power (AUC of 0.54). In a case study of 20 insertion sites in the XynB
      xylanase, two features of native insertion sites showed correlation with the
      splice sites and demonstrated predictive value in selecting non-native splice
      sites. Structural modeling of intein insertions at two sites highlighted the role
      that the insertion site location could play on the ability of the intein to
      modulate activity of the host protein. These findings can be used to enrich the
      selection of insertion sites capable of supporting intein splicing and hosting an
      intein switch.

PMID- 22649522
TI  - Children of low socioeconomic status show accelerated linear growth in early
      childhood; results from the Generation R Study.
AB  - OBJECTIVES: People of low socioeconomic status are shorter than those of high
      socioeconomic status. The first two years of life being critical for height
      development, we hypothesized that a low socioeconomic status is associated with a
      slower linear growth in early childhood. We studied maternal educational level
      (high, mid-high, mid-low, and low) as a measure of socioeconomic status and its
      association with repeatedly measured height in children aged 0-2 years, and also
      examined to what extent known determinants of postnatal growth contribute to this
      association. METHODS: This study was based on data from 2972 mothers with a Dutch
      ethnicity, and their children participating in The Generation R Study, a
      population-based cohort study in Rotterdam, The Netherlands (participation rate
      61%). All children were born between April 2002 and January 2006. Height was
      measured at 2 months (mid-90% range 1.0-3.9), 6 months (mid-90% range 5.6-11.4),
      14 months (mid-90% range 13.7-17.9) and 25 months of age (mid-90% range 23.6
      29.6). RESULTS: At 2 months, children in the lowest educational subgroup were
      shorter than those in the highest (difference: -0.87 cm; 95% CI: -1.16, -0.58).
      Between 1 and 18 months, they grew faster than their counterparts. By 14 months,
      children in the lowest educational subgroup were taller than those in the highest
      (difference at 14 months: 0.40 cm; 95% CI: 0.08,0.72). Adjustment for other
      determinants of postnatal growth did not explain the taller height. On the
      contrary, the differences became even larger (difference at 14 months: 0.61 cm;
      95% CI: 0.26,0.95; and at 25 months: 1.00 cm; 95% CI: 0.57,1.43) CONCLUSIONS:
      Compared with children of high socioeconomic status, those of low socioeconomic
      status show an accelerated linear growth until the 18th month of life, leading to
      an overcompensation of their initial height deficit. The long-term consequences
      of these findings remain unclear and require further study.

PMID- 22649523
TI  - A comparison of Shiga-toxin 2 bacteriophage from classical enterohemorrhagic
      Escherichia coli serotypes and the German E. coli O104:H4 outbreak strain.
AB  - Escherichia coli O104:H4 was associated with a severe foodborne disease outbreak
      originating in Germany in May 2011. More than 4000 illnesses and 50 deaths were
      reported. The outbreak strain was a typical enteroaggregative E. coli (EAEC) that
      acquired an antibiotic resistance plasmid and a Shiga-toxin 2 (Stx2)-encoding
      bacteriophage. Based on whole-genome phylogenies, the O104:H4 strain was most
      closely related to other EAEC strains; however, Stx2-bacteriophage are mobile,
      and do not necessarily share an evolutionary history with their bacterial host.
      In this study, we analyzed Stx2-bacteriophage from the E. coli O104:H4 outbreak
      isolates and compared them to all available Stx2-bacteriophage sequences. We also
      compared Stx2 production by an E. coli O104:H4 outbreak-associated isolate (ON
      2011) to that of E. coli O157:H7 strains EDL933 and Sakai. Among the E. coli Stx2
      phage sequences studied, that from O111:H- strain JB1-95 was most closely related
      phylogenetically to the Stx2-phage from the O104:H4 outbreak isolates. The
      phylogeny of most other Stx2-phage was largely concordant with their bacterial
      host genomes. Finally, O104:H4 strain ON-2011 produced less Stx2 than E. coli
      O157:H7 strains EDL933 and Sakai in culture; however, when mitomycin C was added,
      ON-2011 produced significantly more toxin than the E. coli O157:H7 strains. The
      Stx2-phage from the E. coli O104:H4 outbreak strain and the Stx2-phage from
      O111:H- strain JB1-95 likely share a common ancestor. Incongruence between the
      phylogenies of the Stx2-phage and their host genomes suggest the recent Stx2
      phage acquisition by E. coli O104:H4. The increase in Stx2-production by ON-2011
      following mitomycin C treatment may or may not be related to the high rates of
      hemolytic uremic syndrome associated with the German outbreak strain. Further
      studies are required to determine whether the elevated Stx2-production levels are
      due to bacteriophage or E. coli O104:H4 host related factors.

PMID- 22649525
TI  - Impact of environmental parameters on marathon running performance.
AB  - PURPOSE: The objectives of this study were to describe the distribution of all
      runners' performances in the largest marathons worldwide and to determine which
      environmental parameters have the maximal impact. METHODS: We analysed the
      results of six European (Paris, London, Berlin) and American (Boston, Chicago,
      New York) marathon races from 2001 to 2010 through 1,791,972 participants'
      performances (all finishers per year and race). Four environmental factors were
      gathered for each of the 60 races: temperature ( degrees C), humidity (%), dew
      point ( degrees C), and the atmospheric pressure at sea level (hPA); as well as
      the concentrations of four atmospheric pollutants: NO(2)-SO(2)-O(3) and PM(10)
      (MUg x m(-3)). RESULTS: All performances per year and race are normally
      distributed with distribution parameters (mean and standard deviation) that
      differ according to environmental factors. Air temperature and performance are
      significantly correlated through a quadratic model. The optimal temperatures for
      maximal mean speed of all runners vary depending on the performance level. When
      temperature increases above these optima, running speed decreases and withdrawal
      rates increase. Ozone also impacts performance but its effect might be linked to
      temperature. The other environmental parameters do not have any significant
      impact. CONCLUSIONS: The large amount of data analyzed and the model developed in
      this study highlight the major influence of air temperature above all other
      climatic parameter on human running capacity and adaptation to race conditions.

PMID- 22649524
TI  - A fine-mapping study of 7 top scoring genes from a GWAS for major depressive
      disorder.
AB  - Major depressive disorder (MDD) is a psychiatric disorder that is characterized-
      amongst others--by persistent depressed mood, loss of interest and pleasure and
      psychomotor retardation. Environmental circumstances have proven to influence the
      aetiology of the disease, but MDD also has an estimated 40% heritability,
      probably with a polygenic background. In 2009, a genome wide association study
      (GWAS) was performed on the Dutch GAIN-MDD cohort. A non-synonymous coding single
      nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became only nominally
      significant after post-hoc analysis with an Australian cohort which used similar
      ascertainment. The absence of genome-wide significance may be caused by low SNP
      coverage of genes. To increase SNP coverage to 100% for common variants
      (m.a.f.>0.1, r(2)>0.8), we selected seven genes from the GAIN-MDD GWAS: PCLO,
      GZMK, ANPEP, AFAP1L1, ST3GAL6, FGF14 and PTK2B. We genotyped 349 SNPs and
      obtained the lowest P-value for rs2715147 in PCLO at P = 6.8E-7. We imputed,
      filling in missing genotypes, after which rs2715147 and rs2715148 showed the
      lowest P-value at P = 1.2E-6. When we created a haplotype of these SNPs together
      with the non-synonymous coding SNP rs2522833, the P-value decreased to P = 9.9E-7
      but was not genome wide significant. Although our study did not identify a more
      strongly associated variant, the results for PCLO suggest that the causal variant
      is in high LD with rs2715147, rs2715148 and rs2522833.

PMID- 22649526
TI  - Therapist experience and knowledge acquisition in internet-delivered CBT for
      social anxiety disorder: a randomized controlled trial.
AB  - BACKGROUND: Guided internet-delivered cognitive behavior therapy (ICBT) has been
      tested in several trials on social anxiety disorder (SAD) with moderate to large
      effects. The aims of this study were threefold. First, to compare the effects of
      ICBT including online discussion forum with a moderated online discussion forum
      only. Second, to investigate if knowledge about SAD increased following treatment
      and third to compare the effects of inexperienced versus experienced therapists
      on patient outcomes. METHODS: A total of 204 participants with a primary
      diagnosis of SAD were included and randomized to either guided ICBT or the
      control condition. ICBT consisted of a 9-week treatment program which was guided
      by either psychology students at MSc level (n = 6) or by licensed psychologists
      with previous experience of ICBT (n = 7). A knowledge test dealing with social
      anxiety was administered before and after treatment. Measures of social anxiety
      and secondary outcomes dealing with general anxiety, depression, and quality of
      life were administered before and after treatment. In addition, a 1-year follow
      up was conducted on the treated individuals. RESULTS: Immediately following
      treatment, the ICBT group showed superior outcome on the Liebowitz Social Anxiety
      Scale self-report version with a between group posttreatment Hedges g effect size
      of g = 0.75. In addition, significant differences on all the secondary outcomes
      were observed. Gains were well maintained one year later. Knowledge, as assessed
      by the knowledge test, increased following treatment with little gain in the
      control group. Therapist experience did not result in different outcomes, but
      experienced therapists logged in less frequently compared to the inexperienced
      therapists, suggesting that they needed less time to support patients.
      DISCUSSION: We conclude that guided ICBT reduce symptoms of SAD, increase
      knowledge about SAD and that therapist experience does not make a difference
      apart from the finding that experienced therapist may require less time to guide
      patients. TRIAL REGISTRATION: UMIN.ac.jp UMIN000001383.

PMID- 22649528
TI  - Interaction of virstatin with human serum albumin: spectroscopic analysis and
      molecular modeling.
AB  - Virstatin is a small molecule that inhibits Vibrio cholerae virulence regulation,
      the causative agent for cholera. Here we report the interaction of virstatin with
      human serum albumin (HSA) using various biophysical methods. The drug binding was
      monitored using different isomeric forms of HSA (N form ~pH 7.2, B form ~pH 9.0
      and F form ~pH 3.5) by absorption and fluorescence spectroscopy. There is a
      considerable quenching of the intrinsic fluorescence of HSA on binding the drug.
      The distance (r) between donor (Trp214 in HSA) and acceptor (virstatin), obtained
      from Forster-type fluorescence resonance energy transfer (FRET), was found to be
      3.05 nm. The ITC data revealed that the binding was an enthalpy-driven process
      and the binding constants K(a) for N and B isomers were found to be 6.09*10(5 )M(
      1) and 4.47*10(5) M(-1), respectively. The conformational changes of HSA due to
      the interaction with the drug were investigated from circular dichroism (CD) and
      Fourier Transform Infrared (FTIR) spectroscopy. For 1:1 molar ratio of the
      protein and the drug the far-UV CD spectra showed an increase in alpha- helicity
      for all the conformers of HSA, and the protein is stabilized against urea and
      thermal unfolding. Molecular docking studies revealed possible residues involved
      in the protein-drug interaction and indicated that virstatin binds to Site I
      (subdomain IIA), also known as the warfarin binding site.

PMID- 22649527
TI  - Cysteine peptidases, secreted by Trichomonas gallinae, are involved in the
      cytopathogenic effects on a permanent chicken liver cell culture.
AB  - Trichomonas gallinae, the aetiological agent of avian trichomonosis, was shown to
      secrete soluble factors involved in cytopathogenic effect on a permanent chicken
      liver (LMH) cell culture. The present study focused on the characterization of
      these molecules. The addition of specific peptidase inhibitors to the cell-free
      filtrate partially inhibited the monolayer destruction, which implied the
      presence of peptidases in the filtrate and their involvement in the
      cytopathogenic effect. One-dimensional substrate (gelatin) SDS-PAGE confirmed the
      proteolytic character of the filtrate by demonstrating the proteolytic activity
      within the molecular weight range from 38 to 110 kDa. In addition, the
      proteolytic activity was specifically inhibited by addition of TLCK and E-64
      cysteine peptidase inhibitors implying their cysteine peptidase nature.
      Furthermore, variations in the intensity and the number of proteolytic bands were
      observed between cell-free filtrates of low and high passages of the same T.
      gallinae clonal culture. Two-dimensional substrate gel electrophoresis of
      concentrated T. gallinae cell-free filtrate identified at least six proteolytic
      spots. The mass spectrometric analysis of spots from 2-D gels identified the
      presence of at least two different Clan CA, family C1, cathepsin L-like cysteine
      peptidases in the cell-free filtrate of T. gallinae. In parallel, a PCR approach
      using degenerated primers based on the conserved amino acid sequence region of
      cysteine peptidases from Trichomonas vaginalis identified the coding sequences
      for four different Clan CA, family C1, cathepsin L-like cysteine peptidases.
      Finally, this is the first report analyzing molecules secreted by T. gallinae and
      demonstrating the ubiquity of peptidases secreted by this protozoon.

PMID- 22649529
TI  - The anther steps onto the stigma for self-fertilization in a slipper orchid.
AB  - BACKGROUND: Due to the spatial separation between male and female pollen grains
      from the anther of most flowering plants, including orchids, pollens are
      transported by wind or animals and deposited onto the receptive surface of the
      stigma of a different plant. However, self-pollination is common in pollinating
      animal-scarce habitats. In such habitats, self-pollinations require the
      assistance of a pollinating agent (e.g., wind, gravity, or floral assembly) to
      transport the pollen grains from the anther onto its own stigma.
      METHODOLOGY/PRINCIPAL FINDINGS: Based on observations on floral morphology and
      flowering phenology, tests of the breeding system, and a comparison of
      pollination mechanisms, a new self-pollination process was discovered in the
      hermaphroditic (i.e., possessing spatially separated male and female organs)
      flower of a slipper orchid, Paphiopedilum parishii. The anther changes from a
      solid to a liquid state and directly steps onto the stigma surface without the
      aid of any pollinating agent or floral assembly. CONCLUSIONS: The mode of self
      pollination discussed here is a new addition to the broad range of genetic and
      morphological mechanisms that have evolved in flowering plants to ensure their
      reproductive success. The present self-contained pollination mechanism is a
      possible adaptation to the insect-scarce habitat of the orchid.

PMID- 22649530
TI  - Murine CD4+ T cell responses are inhibited by cytotoxic T cell-mediated killing
      of dendritic cells and are restored by antigen transfer.
AB  - Cytotoxic T lymphocytes (CTL) provide protection against pathogens and tumors. In
      addition, experiments in mouse models have shown that CTL can also kill antigen
      presenting dendritic cells (DC), reducing their ability to activate primary and
      secondary CD8(+) T cell responses. In contrast, the effects of CTL-mediated
      killing on CD4(+) T cell responses have not been fully investigated. Here we use
      adoptive transfer of TCR transgenic T cells and DC immunization to show that
      specific CTL significantly inhibited CD4(+) T cell proliferation induced by DC
      loaded with peptide or low concentrations of protein antigen. In contrast, CTL
      had little effect on CD4(+) T cell proliferation induced by DC loaded with high
      protein concentrations or expressing antigen endogenously, even if these DC were
      efficiently killed and failed to accumulate in the lymph node (LN). Residual
      CD4(+) T cell proliferation was due to the transfer of antigen from carrier DC to
      host APC, and predominantly involved skin DC populations. Importantly, the
      proliferating CD4(+) T cells also developed into IFN-gamma producing memory
      cells, a property normally requiring direct presentation by activated DC. Thus,
      CTL-mediated DC killing can inhibit CD4(+) T cell proliferation, with the extent
      of inhibition being determined by the form and amount of antigen used to load DC.
      In the presence of high antigen concentrations, antigen transfer to host DC
      enables the generation of CD4(+) T cell responses regardless of DC killing, and
      suggests mechanisms whereby CD4(+) T cell responses can be amplified.

PMID- 22649531
TI  - Simple ways to measure behavioral responses of Drosophila to stimuli and use of
      these methods to characterize a novel mutant.
AB  - The behavioral responses of adult Drosophila fruit flies to a variety of sensory
      stimuli--light, volatile and non-volatile chemicals, temperature, humidity,
      gravity, and sound--have been measured by others previously. Some of those assays
      are rather complex; a review of them is presented in the Discussion. Our
      objective here has been to find out how to measure the behavior of adult
      Drosophila fruit flies by methods that are inexpensive and easy to carry out.
      These new assays have now been used here to characterize a novel mutant that
      fails to be attracted or repelled by a variety of sensory stimuli even though it
      is motile.

PMID- 22649532
TI  - Global activation of CD8+ cytotoxic T lymphocytes correlates with an impairment
      in regulatory T cells in patients with generalized vitiligo.
AB  - Melanocyte-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a pivotal role in
      vitiligo-induced depigmentation. Yet, the mechanisms underlying the high
      frequency of generalized autoimmune disorders associated with generalized
      vitiligo (GV) are unknown. We hypothesized that an imbalance between activated
      CD8(+) CTLs and regulatory T cells (Tregs) exists in patients with GV .
      Assessment of the circulating CD8(+) CTLs and Tregs by flow cytometric analysis
      revealed an obvious expansion of CD8(+) CTLs and a concomitant decrease in Treg
      cells in GV patients. The percentages of skin infiltrating CD8(+) CTLs and Tregs
      were evaluated by immunohistochemistry and revealed dramatically increased
      numbers of both CD8(+) CTLs and Tregs in the perilesional skin of GV patients.
      However, peripheral Tregs were impaired in their ability to suppress the
      proliferation and cytolytic capacity of autologous CD8(+) T cells, suggesting
      that a functional failure of Tregs and the hyper-activation of CD8(+) CTLs may
      contribute to progressive GV. Our data indicate that reduced numbers and impaired
      function of natural Tregs fail to control the widespread activation of CD8(+)
      CTLs, which leads to the destruction of melanocytes and contributes to the
      elevated frequency of various associated autoimmune diseases. This knowledge
      furthers our understanding of the mechanisms of immune tolerance that are
      impaired in GV patients and may aid in the future development of effective
      immunotherapy for GV patients.

PMID- 22649533
TI  - Recent and projected increases in atmospheric CO2 concentration can enhance gene
      flow between wild and genetically altered rice (Oryza sativa).
AB  - Although recent and projected increases in atmospheric carbon dioxide can alter
      plant phenological development, these changes have not been quantified in terms
      of floral outcrossing rates or gene transfer. Could differential phenological
      development in response to rising CO(2) between genetically modified crops and
      wild, weedy relatives increase the spread of novel genes, potentially altering
      evolutionary fitness? Here we show that increasing CO(2) from an early 20(th)
      century concentration (300 umol mol(-1)) to current (400 umol mol(-1)) and
      projected, mid-21(st) century (600 umol mol(-1)) values, enhanced the flow of
      genes from wild, weedy rice to the genetically altered, herbicide resistant,
      cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300
      to 600 umol mol(-1). The increase in outcrossing and gene transfer was associated
      with differential increases in plant height, as well as greater tiller and
      panicle production in the wild, relative to the cultivated population. In
      addition, increasing CO(2) also resulted in a greater synchronicity in flowering
      times between the two populations. The observed changes reported here resulted in
      a subsequent increase in rice dedomestication and a greater number of weedy,
      herbicide-resistant hybrid progeny. Overall, these data suggest that differential
      phenological responses to rising atmospheric CO(2) could result in enhanced flow
      of novel genes and greater success of feral plant species in agroecosystems.

PMID- 22649534
TI  - Expression-dependent folding of interphase chromatin.
AB  - Multiple studies suggest that chromatin looping might play a crucial role in
      organizing eukaryotic genomes. To investigate the interplay between the
      conformation of interphase chromatin and its transcriptional activity, we include
      information from gene expression profiles into a polymer model for chromatin that
      incorporates genomic loops. By relating loop formation to transcriptional
      activity, we are able to generate chromosome conformations whose structural and
      topological properties are consistent with experimental data. The model
      particularly allows to reproduce the conformational variations that are known to
      occur between highly and lowly expressed chromatin regions. As previously
      observed in experiments, lowly expressed regions of the simulated polymers are
      much more compact. Due to the changes in loop formation, the distributions of
      chromatin loops are also expression-dependent and exhibit a steeper decay in
      highly active regions. As a results of entropic interaction between differently
      looped parts of the chromosome, we observe topological alterations leading to a
      preferential positioning of highly transcribed loci closer to the surface of the
      chromosome territory. Considering the diffusional behavior of the chromatin
      fibre, the simulations furthermore show that the higher the expression level of
      specific parts of the chromatin fibre is, the more dynamic they are. The results
      exhibit that variations of loop formation along the chromatin fibre, and the
      entropic changes that come along with it, do not only influence the structural
      parameters on the local scale, but also effect the global chromosome conformation
      and topology.

PMID- 22649535
TI  - Chondrocyte deformations as a function of tibiofemoral joint loading predicted by
      a generalized high-throughput pipeline of multi-scale simulations.
AB  - Cells of the musculoskeletal system are known to respond to mechanical loading
      and chondrocytes within the cartilage are not an exception. However,
      understanding how joint level loads relate to cell level deformations, e.g. in
      the cartilage, is not a straightforward task. In this study, a multi-scale
      analysis pipeline was implemented to post-process the results of a macro-scale
      finite element (FE) tibiofemoral joint model to provide joint mechanics based
      displacement boundary conditions to micro-scale cellular FE models of the
      cartilage, for the purpose of characterizing chondrocyte deformations in relation
      to tibiofemoral joint loading. It was possible to identify the load distribution
      within the knee among its tissue structures and ultimately within the cartilage
      among its extracellular matrix, pericellular environment and resident
      chondrocytes. Various cellular deformation metrics (aspect ratio change,
      volumetric strain, cellular effective strain and maximum shear strain) were
      calculated. To illustrate further utility of this multi-scale modeling pipeline,
      two micro-scale cartilage constructs were considered: an idealized single cell at
      the centroid of a 100*100*100 MUm block commonly used in past research studies,
      and an anatomically based (11 cell model of the same volume) representation of
      the middle zone of tibiofemoral cartilage. In both cases, chondrocytes
      experienced amplified deformations compared to those at the macro-scale,
      predicted by simulating one body weight compressive loading on the tibiofemoral
      joint. In the 11 cell case, all cells experienced less deformation than the
      single cell case, and also exhibited a larger variance in deformation compared to
      other cells residing in the same block. The coupling method proved to be highly
      scalable due to micro-scale model independence that allowed for exploitation of
      distributed memory computing architecture. The method's generalized nature also
      allows for substitution of any macro-scale and/or micro-scale model providing
      application for other multi-scale continuum mechanics problems.

PMID- 22649537
TI  - Genetic analysis of the electrophysiological response to salicin, a bitter
      substance, in a polyphagous strain of the silkworm Bombyx mori.
AB  - Sawa-J is a polyphagous silkworm (Bombyx mori L.) strain that eats various plant
      leaves that normal silkworms do not. The feeding preference behavior of Sawa-J is
      controlled by one major recessive gene(s) on the polyphagous (pph) locus, and
      several minor genes; moreover, its deterrent cells possess low sensitivity to
      some bitter substances including salicin. To clarify whether taste sensitivity is
      controlled by the pph locus, we conducted a genetic analysis of the
      electrophysiological characteristics of the taste response using the polyphagous
      strain Sawa-J.lem, in which pph is linked to the visible larval marker lemon
      (lem) on the third chromosome, and the normal strain Daiankyo, in which the wild
      type gene of pph (+(pph)) is marked with Zebra (Ze). Maxillary taste neurons of
      the two strains had similar dose-response relationships for sucrose, inositol,
      and strychnine nitrate, but the deterrent cell of Sawa-J.lem showed a remarkably
      low sensitivity to salicin. The F(1) generation of the two strains had
      characteristics similar to the Daiankyo strain, consistent with the idea that pph
      is recessive. In the BF(1) progeny between F(1) females and Sawa-J.lem males
      where no crossing-over occurs, the lem and Ze phenotypes corresponded to
      different electrophysiological reactions to 25 mM salicin, indicating that the
      gene responsible for taste sensitivity to salicin is located on the same
      chromosome as the lem and Ze genes. The normal and weak reactions to 25 mM
      salicin were segregated in crossover-type larvae of the BF(1) progeny produced by
      a reciprocal cross, and the recombination frequency agreed well with the
      theoretical ratio for the loci of lem, pph, and Ze on the standard linkage map.
      These results indicate that taste sensitivity to salicin is controlled by the
      gene(s) on the pph locus.

PMID- 22649536
TI  - Digits lost or gained? Evidence for pedal evolution in the dwarf salamander
      complex (Eurycea, Plethodontidae).
AB  - Change in digit number, particularly digit loss, has occurred repeatedly over the
      evolutionary history of tetrapods. Although digit loss has been documented among
      distantly related species of salamanders, it is relatively uncommon in this
      amphibian order. For example, reduction from five to four toes appears to have
      evolved just three times in the morphologically and ecologically diverse family
      Plethodontidae. Here we report a molecular phylogenetic analysis for one of these
      four-toed lineages--the Eurycea quadridigitata complex (dwarf salamanders)-
      emphasizing relationships to other species in the genus. A multilocus phylogeny
      reveals that dwarf salamanders are paraphyletic with respect to a complex of five
      toed, paedomorphic Eurycea from the Edwards Plateau in Texas. We use this
      phylogeny to examine evolution of digit number within the dwarf-Edwards Plateau
      clade, testing contrasting hypotheses of digit loss (parallelism among dwarf
      salamanders) versus digit gain (re-evolution in the Edwards Plateau complex).
      Bayes factors analysis provides statistical support for a five-toed common
      ancestor at the dwarf-Edwards node, favoring, slightly, the parallelism
      hypothesis for digit loss. More importantly, our phylogenetic results pinpoint a
      rare event in the pedal evolution of plethodontid salamanders.

PMID- 22649538
TI  - Development of cysteine-free fluorescent proteins for the oxidative environment.
AB  - Molecular imaging employing fluorescent proteins has been widely used to
      highlight specific reactions or processes in various fields of the life sciences.
      Despite extensive improvements of the fluorescent tag, this technology is still
      limited in the study of molecular events in the extracellular milieu. This is
      partly due to the presence of cysteine in the fluorescent proteins. These
      proteins almost cotranslationally form disulfide bonded oligomers when expressed
      in the endoplasmic reticulum (ER). Although single molecule photobleaching
      analysis showed that these oligomers were not fluorescent, the fluorescent
      monomer form often showed aberrant behavior in folding and motion, particularly
      when fused to cysteine-containing cargo. Therefore we investigated whether it was
      possible to eliminate the cysteine without losing the brightness. By site
      saturated mutagenesis, we found that the cysteine residues in fluorescent
      proteins could be replaced with specific alternatives while still retaining their
      brightness. cf(cysteine-free)SGFP2 showed significantly reduced restriction of
      free diffusion in the ER and marked improvement of maturation when fused to the
      prion protein. We further applied this approach to TagRFP family proteins and
      found a set of mutations that obtains the same level of brightness as the
      cysteine-containing proteins. The approach used in this study to generate new
      cysteine-free fluorescent tags should expand the application of molecular imaging
      to the extracellular milieu and facilitate its usage in medicine and
      biotechnology.

PMID- 22649539
TI  - Direct heme transfer reactions in the Group A Streptococcus heme acquisition
      pathway.
AB  - The heme acquisition machinery in Group A Streptococcus (GAS) consists of the
      surface proteins Shr and Shp and ATP-binding cassette transporter HtsABC. Shp
      cannot directly acquire heme from methemoglobin (metHb) but directly transfers
      its heme to HtsA. It has not been previously determined whether Shr directly
      relays heme from metHb to Shp. Thus, the complete pathway for heme acquisition
      from metHb by the GAS heme acquisition machinery has remained unclear. In this
      study, the metHb-to-Shr and Shr-to-Shp heme transfer reactions were characterized
      by spectroscopy, kinetics and protein-protein interaction analyses. Heme is
      efficiently transferred from the beta and alpha subunits of metHb to Shr with
      rates that are 7 and 60 times greater than those of the passive heme release from
      metHb, indicating that Shr directly acquires heme from metHb. The rapid heme
      transfer from Shr to Shp involves an initial heme donor/acceptor complex and a
      spectrally and kinetically detectable transfer intermediate, implying that heme
      is directly channeled from Shr to Shp. The present results show that Shr speeds
      up heme transfer from metHb to Shp, whereas Shp speeds up heme transfer from Shr
      to HtsA. Furthermore, the findings demonstrate that Shr can interact with metHb
      and Shp but not HtsA. Taken together with our published results on the Shp/HtsA
      reaction, these findings establish a model of the heme acquisition pathway in GAS
      in which Shr directly extracts heme from metHb and Shp relays it from Shr to
      HtsA.

PMID- 22649540
TI  - Genome characteristics of a novel phage from Bacillus thuringiensis showing high
      similarity with phage from Bacillus cereus.
AB  - Bacillus thuringiensis is an important entomopathogenic bacterium belongs to the
      Bacillus cereus group, which also includes B. anthracis and B. cereus. Several
      genomes of phages originating from this group had been sequenced, but no genome
      of Siphoviridae phage from B. thuringiensis has been reported. We recently
      sequenced and analyzed the genome of a novel phage, BtCS33, from a B.
      thuringiensis strain, subsp. kurstaki CS33, and compared the gneome of this phage
      to other phages of the B. cereus group. BtCS33 was the first Siphoviridae phage
      among the sequenced B. thuringiensis phages. It produced small, turbid plaques on
      bacterial plates and had a narrow host range. BtCS33 possessed a linear, double
      stranded DNA genome of 41,992 bp with 57 putative open reading frames (ORFs). It
      had a typical genome structure consisting of three modules: the "late" region,
      the "lysogeny-lysis" region and the "early" region. BtCS33 exhibited high
      similarity with several phages, B. cereus phage Wbeta and some variants of Wbeta,
      in genome organization and the amino acid sequences of structural proteins. There
      were two ORFs, ORF22 and ORF35, in the genome of BtCS33 that were also found in
      the genomes of B. cereus phage Wbeta and may be involved in regulating
      sporulation of the host cell. Based on these observations and analysis of
      phylogenetic trees, we deduced that B. thuringiensis phage BtCS33 and B. cereus
      phage Wbeta may have a common distant ancestor.

PMID- 22649541
TI  - Is promiscuity associated with enhanced selection on MHC-DQalpha in mice (genus
      Peromyscus)?
AB  - Reproductive behavior may play an important role in shaping selection on Major
      Histocompatibility Complex (MHC) genes. For example, the number of sexual
      partners that an individual has may affect exposure to sexually transmitted
      pathogens, with more partners leading to greater exposure and, hence, potentially
      greater selection for variation at MHC loci. To explore this hypothesis, we
      examined the strength of selection on exon 2 of the MHC-DQalpha locus in two
      species of Peromyscus. While the California mouse (P. californicus) is
      characterized by lifetime social and genetic monogamy, the deer mouse (P.
      maniculatus) is socially and genetically promiscuous; consistent with these
      differences in mating behavior, the diversity of bacteria present within the
      reproductive tracts of females is significantly greater for P. maniculatus. To
      test the prediction that more reproductive partners and exposure to a greater
      range of sexually transmitted pathogens are associated with enhanced diversifying
      selection on genes responsible for immune function, we compared patterns and
      levels of diversity at the Class II MHC-DQalpha locus in sympatric populations of
      P. maniculatus and P. californicus. Using likelihood based analyses, we show that
      selection is enhanced in the promiscuous P. maniculatus. This study is the first
      to compare the strength of selection in wild sympatric rodents with known
      differences in pathogen milieu.

PMID- 22649542
TI  - Camouflaging in a complex environment--octopuses use specific features of their
      surroundings for background matching.
AB  - Living under intense predation pressure, octopuses evolved an effective and
      impressive camouflaging ability that exploits features of their surroundings to
      enable them to "blend in." To achieve such background matching, an animal may use
      general resemblance and reproduce characteristics of its entire surroundings, or
      it may imitate a specific object in its immediate environment. Using image
      analysis algorithms, we examined correlations between octopuses and their
      backgrounds. Field experiments show that when camouflaging, Octopus cyanea and O.
      vulgaris base their body patterns on selected features of nearby objects rather
      than attempting to match a large field of view. Such an approach enables the
      octopus to camouflage in partly occluded environments and to solve the problem of
      differences in appearance as a function of the viewing inclination of the
      observer.

PMID- 22649544
TI  - Climate driven egg and hatchling mortality threatens survival of eastern Pacific
      leatherback turtles.
AB  - Egg-burying reptiles need relatively stable temperature and humidity in the
      substrate surrounding their eggs for successful development and hatchling
      emergence. Here we show that egg and hatchling mortality of leatherback turtles
      (Dermochelys coriacea) in northwest Costa Rica were affected by climatic
      variability (precipitation and air temperature) driven by the El Nino Southern
      Oscillation (ENSO). Drier and warmer conditions associated with El Nino increased
      egg and hatchling mortality. The fourth assessment report of the
      Intergovernmental Panel on Climate Change (IPCC) projects a warming and drying in
      Central America and other regions of the World, under the SRES A2 development
      scenario. Using projections from an ensemble of global climate models contributed
      to the IPCC report, we project that egg and hatchling survival will rapidly
      decline in the region over the next 100 years by ~50-60%, due to warming and
      drying in northwestern Costa Rica, threatening the survival of leatherback
      turtles. Warming and drying trends may also threaten the survival of sea turtles
      in other areas affected by similar climate changes.

PMID- 22649543
TI  - Functional characterization of an Aspergillus fumigatus calcium transporter
      (PmcA) that is essential for fungal infection.
AB  - Aspergillus fumigatus is a primary and opportunistic pathogen, as well as a major
      allergen, of mammals. The Ca(+2)-calcineurin pathway affects virulence,
      morphogenesis and antifungal drug action in A. fumigatus. Here, we investigated
      three components of the A. fumigatus Ca(+2)-calcineurin pathway, pmcA,-B, and -C,
      which encode calcium transporters. We demonstrated that CrzA can directly control
      the mRNA accumulation of the pmcA-C genes by binding to their promoter regions.
      CrzA-binding experiments suggested that the 5'-CACAGCCAC-3' and 5'-CCCTGCCCC-3'
      sequences upstream of pmcA and pmcC genes, respectively, are possible calcineurin
      dependent response elements (CDREs)-like consensus motifs. Null mutants were
      constructed for pmcA and -B and a conditional mutant for pmcC demonstrating pmcC
      is an essential gene. The DeltapmcA and DeltapmcB mutants were more sensitive to
      calcium and resistant to manganese and cyclosporin was able to modulate the
      sensitivity or resistance of these mutants to these salts, supporting the
      interaction between calcineurin and the function of these transporters. The pmcA
      C genes have decreased mRNA abundance into the alveoli in the DeltacalA and
      DeltacrzA mutant strains. However, only the A. fumigatus DeltapmcA was avirulent
      in the murine model of invasive pulmonary aspergillosis.

PMID- 22649545
TI  - Expression of dickkopf-1 and beta-catenin related to the prognosis of breast
      cancer patients with triple negative phenotype.
AB  - BACKGROUND AND AIM: We investigated the prognostic importance of dickkopf-1(DKK1)
      and beta-catenin expression in triple negative breast cancers. METHODS: The
      expression of DKK1 and beta-catenin was evaluated in breast cell lines using RT
      PCR and western blot. Immunohistochemistry was used to characterize the
      expression pattern of DKK1 and beta-catenin in 85 triple negative breast cancers
      and prognostic significance was assessed by Kaplan-Meier analysis and Cox
      proportional hazards regression modeling. RESULTS: The expression of DKK1 was
      confirmed in hormone-resistant breast cell lines MDA-MB-231, MDA-MB-231-HM and
      MDA-MB-435. Expression of DKK1 in triple negative breast cancers correlated with
      cytoplasmic/nuclear beta-catenin (p = 0.000). Elevated expression of DKK1 and
      cytoplasmic/nuclear beta-catenin in triple negative cancers indicate poor outcome
      of patients. DKK1 was also a prognostic factor for patients with earlier stage or
      no lymph node metastasis. CONCLUSION: DKK1 together with beta-catenin might be
      important prognostic factors in triple negative breast carcinoma. DKK1 might be a
      valuable biomarker in predicting the prognosis of patients with earlier stage or
      no lymph node metastasis. It is possible that through further understanding of
      the role of Wnt/beta-catenin pathway activation, beta-catenin would be a
      potential therapeutic target for the triple negative breast cancer.

PMID- 22649546
TI  - A novel tool for studying auxin-metabolism: the inhibition of grapevine indole-3
      acetic acid-amido synthetases by a reaction intermediate analogue.
AB  - An important process for the regulation of auxin levels in plants is the
      inactivation of indole-3-acetic acid (IAA) by conjugation to amino acids. The
      conjugation reaction is catalysed by IAA-amido synthetases belonging to the
      family of GH3 proteins. Genetic approaches to study the biological significance
      of these enzymes have been hampered by large gene numbers and a high degree of
      functional redundancy. To overcome these difficulties a chemical approach based
      on the reaction mechanism of GH3 proteins was employed to design a small molecule
      inhibitor of IAA-amido synthetase activity. Adenosine-5'-[2-(1H-indol-3
      yl)ethyl]phosphate (AIEP) mimics the adenylated intermediate of the IAA
      conjugation reaction and was therefore proposed to compete with the binding of
      MgATP and IAA in the initial stages of catalysis. Two grapevine IAA-amido
      synthetases with different catalytic properties were chosen to test the
      inhibitory effects of AIEP in vitro. GH3-1 has previously been implicated in the
      grape berry ripening process and is restricted to two amino acid substrates,
      whereas GH3-6 conjugated IAA to 13 amino acids. AIEP is the most potent inhibitor
      of GH3 enzymes so far described and was shown to be competitive against MgATP and
      IAA binding to both enzymes with K(i)-values 17-68-fold lower than the respective
      K(m)-values. AIEP also exhibited in vivo activity in an ex planta test system
      using young grape berries. Exposure to 5-20 uM of the inhibitor led to decreased
      levels of the common conjugate IAA-Asp and reduced the accumulation of the
      corresponding Asp-conjugate upon treatment with a synthetic auxin. AIEP therefore
      represents a novel chemical probe with which to study IAA-amido synthetase
      function.

PMID- 22649548
TI  - Clinical usefulness of measuring red blood cell distribution width in patients
      with hepatitis B.
AB  - BACKGROUND: Red blood cell distribution width (RDW), an automated measure of red
      blood cell size heterogeneity (e.g., anisocytosis) that is largely overlooked, is
      a newly recognized risk marker in patients with cardiovascular diseases, but its
      role in persistent viral infection has not been well-defined. The present study
      was designed to investigate the association between RDW values and different
      disease states in hepatitis B virus (HBV)-infected patients. In addition, we
      analyzed whether RDW is associated with mortality in the HBV-infected patients.
      METHODOLOGY/PRINCIPAL FINDINGS: One hundred and twenty-three patients, including
      16 with acute hepatitis B (AHB), 61 with chronic hepatitis B (CHB), and 46 with
      chronic severe hepatitis B (CSHB), and 48 healthy controls were enrolled. In all
      subjects, a blood sample was collected at admission to examine liver function,
      renal function, international normalized ratio and routine hematological testing.
      All patients were followed up for at least 4 months. A total of 10 clinical
      chemistry, hematology, and biochemical variables were analyzed for possible
      association with outcomes by using Cox proportional hazards and multiple
      regression models. RDW values at admission in patients with CSHB (18.30+/-3.11%,
      P<0.001), CHB (16.37+/-2.43%, P<0.001) and AHB (14.38+/-1.72%, P<0.05) were
      significantly higher than those in healthy controls (13.03+/-1.33%). Increased
      RDW values were clinically associated with severe liver disease and increased 3
      month mortality rate. Multivariate analysis demonstrated that RDW values and the
      model for end-stage liver disease score were independent predictors for mortality
      (both P<0.001). CONCLUSION: RDW values are significantly increased in patients
      with hepatitis B and associated with its severity. Moreover, RDW values are an
      independent predicting factor for the 3-month mortality rate in patients with
      hepatitis B.

PMID- 22649547
TI  - NF-kappaB repression by PIAS3 mediated RelA SUMOylation.
AB  - Negative regulation of the NF-kappaB transcription factor is essential for tissue
      homeostasis in response to stress and inflammation. NF-kappaB activity is
      regulated by a variety of biochemical mechanisms including phosphorylation,
      acetylation, and ubiquitination. In this study, we provide the first experimental
      evidence that NF-kappaB is regulated by SUMOylation, where the RelA subunit of NF
      kappaB is SUMOylated by PIAS3, a member of the PIAS (protein inhibitor of
      activated STAT) protein family with E3 SUMO ligase activity. PIAS3-mediated NF
      kappaB repression was compromised by either RelA mutant resistant to SUMOylation
      or PIAS3 mutant defective in SUMOylation. PIAS3-mediated SUMOylation of
      endogenous RelA was induced by NF-kappaB activation thus forming a negative
      regulatory loop. The SUMOylation of endogenous RelA was enhanced in IkappaBalpha
      null as compared with wild type fibroblasts. The RelA SUMOylation was induced by
      TNFalpha but not leptomycin B mediated RelA nuclear translocation. Furthermore,
      RelA mutants defective in DNA binding were not SUMOylated by PIAS3, suggesting
      that RelA DNA binding is a signal for PIAS3-mediated SUMOylation. These results
      support a novel negative feedback mechanism for NF-kappaB regulation by PIAS3
      mediated RelA SUMOylation.

PMID- 22649549
TI  - Loss of STAT1 in bone marrow-derived cells accelerates skeletal muscle
      regeneration.
AB  - BACKGROUND: Skeletal muscle regeneration is a complex process which is not yet
      completely understood. Evidence suggested that the Janus kinase (JAK)-signal
      transducer and activator of transcription (STAT) pathway may have a role in
      myogenesis. In this study, we aim to explore the possible role of STAT1 in muscle
      regeneration. METHODS: Wild-type and STAT1 knockout mice were used in this study.
      Tibialis anterior muscle injury was conducted by cardiotoxin (CTX) injection.
      Bone marrow transplantation and glucocorticoid treatment were performed to
      manipulate the immune system of the mice. RESULTS: Muscle regeneration was
      accelerated in STAT1-/- mice after CTX injury. Bone marrow transplantation
      experiments showed that the regeneration process relied on the type of donor mice
      rather than on recipient mice. Levels of pro-inflammatory cytokines, TNFalpha and
      IL-1beta, were significantly higher in STAT1-/- mice at 1 day and/or 2 days post
      injury, while levels of anti-inflammatory cytokine, IL-10, were lower in STAT1-/-
      mice at 2 days and 3 days post-injury. Levels of IGF-1 were significantly higher
      in the STAT1-/- mice at 1 day and 2 days post-injury. Furthermore, the muscle
      regeneration process was inhibited in glucocorticoid-treated mice. CONCLUSIONS:
      Loss of STAT1 in bone marrow-derived cells accelerates skeletal muscle
      regeneration.

PMID- 22649550
TI  - Environmental perturbation of the circadian clock disrupts pregnancy in the
      mouse.
AB  - BACKGROUND: The circadian clock has been linked to reproduction at many levels in
      mammals. Epidemiological studies of female shift workers have reported increased
      rates of reproductive abnormalities and adverse pregnancy outcomes, although
      whether the cause is circadian disruption or another factor associated with shift
      work is unknown. Here we test whether environmental disruption of circadian
      rhythms, using repeated shifts of the light:dark (LD) cycle, adversely affects
      reproductive success in mice. METHODOLOGY/PRINCIPAL FINDINGS: Young adult female
      C57BL/6J (B6) mice were paired with B6 males until copulation was verified by
      visual identification of vaginal plug formation. Females were then randomly
      assigned to one of three groups: control, phase-delay or phase-advance. Controls
      remained on a constant 12-hr light:12-hr dark cycle, whereas phase-delayed and
      phase-advanced mice were subjected to 6-hr delays or advances in the LD cycle
      every 5-6 days, respectively. The number of copulations resulting in term
      pregnancies was determined. Control females had a full-term pregnancy success
      rate of 90% (11/12), which fell to 50% (9/18; p<0.1) in the phase-delay group and
      22% (4/18; p<0.01) in the phase-advance group. CONCLUSIONS/SIGNIFICANCE: Repeated
      shifting of the LD cycle, which disrupts endogenous circadian timekeeping,
      dramatically reduces pregnancy success in mice. Advances of the LD cycle have a
      greater negative impact on pregnancy outcomes and, in non-pregnant female mice,
      require longer for circadian re-entrainment, suggesting that the magnitude or
      duration of circadian misalignment may be related to the severity of the adverse
      impact on pregnancy. These results explicitly link disruptions of circadian
      entrainment to adverse pregnancy outcomes in mammals, which may have important
      implications for the reproductive health of female shift workers, women with
      circadian rhythm sleep disorders and/or women with disturbed circadian rhythms
      for other reasons.

PMID- 22649551
TI  - Population receptive field dynamics in human visual cortex.
AB  - Seminal work in the early nineties revealed that the visual receptive field of
      neurons in cat primary visual cortex can change in location and size when
      artificial scotomas are applied. Recent work now suggests that these single
      neuron receptive field dynamics also pertain to the neuronal population receptive
      field (pRF) that can be measured in humans with functional magnetic resonance
      imaging (fMRI). To examine this further, we estimated the pRF in twelve healthy
      participants while masking the central portion of the visual field. We found that
      the pRF changes in location and size for two differently sized artificial
      scotomas, and that these pRF dynamics are most likely due to a combination of the
      neuronal receptive field position and size scatter as well as modulatory feedback
      signals from extrastriate visual areas.

PMID- 22649552
TI  - Inflammasome-mediated IL-1beta production in humans with cystic fibrosis.
AB  - BACKGROUND: Inflammation and infection are major determinants of disease severity
      and consequently, the quality of life and outcome for patients with cystic
      fibrosis (CF). Interleukin-1 beta (IL-1beta) is a key inflammatory mediator.
      Secretion of biologically active IL-1beta involves inflammasome-mediated
      processing. Little is known about the contribution of IL-1beta and the
      inflammasomes in CF inflammatory disease. This study examines inflammasome
      mediated IL-1beta production in CF bronchial epithelial cell lines and human
      patients with CF. RESULTS: Bronchial epithelial cell lines were found to produce
      negligible amounts of basal or stimulated IL-1beta compared to hematopoeitic
      cells and they did not significantly upregulate caspase-1 activity upon
      inflammasome stimulation. In contrast, peripheral blood mononuclear cells (PBMCs)
      from both CF and healthy control subjects produced large amounts of IL-1beta and
      strongly upregulated caspase-1 activity upon inflammasome stimulation. PBMCs from
      CF patients and controls displayed similar levels of caspase-1 activation and IL
      1beta production when stimulated with inflammasome activators. This IL-1beta
      production was dependent on NF-kappaB activity and could be enhanced by priming
      with LPS. Finally, chemical inhibition of CFTR activity in control PBMCs and THP
      1 cells did not significantly alter IL-1beta or IL-8 production in response to P.
      aeruginosa. CONCLUSION: Hematopoeitic cells appear to be the predominant source
      of inflammasome-induced pro-inflammatory IL-1beta in CF. PBMCs derived from CF
      subjects display preserved inflammasome activation and IL-1beta secretion in
      response to the major CF pathogen Pseudomonas aeruginosa. However, our data do
      not support the hypothesis that increased IL-1beta production in CF subjects is
      due to an intrinsic increase in NF-kappaB activity through loss of CFTR function.

PMID- 22649553
TI  - Variation in size and growth of the great scallop Pecten maximus along a
      latitudinal gradient.
AB  - Understanding the relationship between growth and temperature will aid in the
      evaluation of thermal stress and threats to ectotherms in the context of
      anticipated climate changes. Most Pecten maximus scallops living at high
      latitudes in the northern hemisphere have a larger maximum body size than
      individuals further south, a common pattern among many ectotherms. We
      investigated differences in daily shell growth among scallop populations along
      the Northeast Atlantic coast from Spain to Norway. This study design allowed us
      to address precisely whether the asymptotic size observed along a latitudinal
      gradient, mainly defined by a temperature gradient, results from differences in
      annual or daily growth rates, or a difference in the length of the growing
      season. We found that low annual growth rates in northern populations are not due
      to low daily growth values, but to the smaller number of days available each year
      to achieve growth compared to the south. We documented a decrease in the annual
      number of growth days with age regardless of latitude. However, despite initially
      lower annual growth performances in terms of growing season length and growth
      rate, differences in asymptotic size as a function of latitude resulted from
      persistent annual growth performances in the north and sharp declines in the
      south. Our measurements of daily growth rates throughout life in a long-lived
      ectothermic species provide new insight into spatio-temporal variations in growth
      dynamics and growing season length that cannot be accounted for by classical
      growth models that only address asymptotic size and annual growth rate.

PMID- 22649554
TI  - Isolates of Liao ning virus from wild-caught mosquitoes in the Xinjiang province
      of China in 2005.
AB  - Liao ning virus (LNV) is related to Banna virus, a known human-pathogen present
      in south-east Asia. Both viruses belong to the genus Seadornavirus, family
      Reoviridae. LNV causes lethal haemorrhage in experimentally infected mice. Twenty
      seven isolates of LNV were made from mosquitoes collected in different locations
      within the Xinjiang province of north-western China during 2005. These mosquitoes
      were caught in the accommodation of human patients with febrile manifestations,
      or in animal barns where sheep represent the main livestock species. The regions
      where LNV was isolated are affected by seasonal encephalitis, but are free of
      Japanese encephalitis (JE). Genome segment 10 (Seg-10) (encoding cell-attachment
      and serotype-determining protein VP10) and Seg-12 (encoding non-structural
      protein VP12) were sequenced for multiple LNV isolates. Phylogenetic analyses
      showed a less homogenous Seg-10 gene pool, as compared to segment 12. However,
      all of these isolates appear to belong to LNV type-1. These data suggest a
      relatively recent introduction of LNV into Xinjiang province, with substitution
      rates for LNV Seg-10 and Seg-12, respectively, of 2.29*10(-4) and 1.57*10(-4)
      substitutions/nt/year. These substitution rates are similar to those estimated
      for other dsRNA viruses. Our data indicate that the history of LNV is
      characterized by a lack of demographic fluctuations. However, a decline in the
      LNV population in the late 1980s-early 1990s, was indicated by data for both Seg
      10 and Seg-12. Data also suggest a beginning of an expansion in the late 1990s as
      inferred from Seg-12 skyline plot.

PMID- 22649555
TI  - Expansion and evolution of the X-linked testis specific multigene families in the
      melanogaster species subgroup.
AB  - The testis specific X-linked genes whose evolution is traced here in the
      melanogaster species subgroup are thought to undergo fast rate of
      diversification. The CK2betates and NACbetates gene families encode the diverged
      regulatory beta-subunits of protein kinase CK2 and the homologs of beta-subunit
      of nascent peptide associated complex, respectively. We annotated the CK2betates
      like genes related to CK2betates family in the D. simulans and D. sechellia
      genomes. The ancestor CK2betates-like genes preserved in D. simulans and D.
      sechellia are considered to be intermediates in the emergence of the D.
      melanogaster specific Stellate genes related to the CK2betates family. The
      CK2betates-like genes are more similar to the unique autosomal CK2betates gene
      than to Stellates, taking into account their peculiarities of polymorphism. The
      formation of a variant the CK2betates gene Stellate in D. melanogaster as a
      result of illegitimate recombination between a NACbetates promoter and a distinct
      polymorphic variant of CK2betates-like ancestor copy was traced. We found a close
      nonrandom proximity between the dispersed defective copies of DINE-1 transposons,
      the members of Helitron family, and the CK2betates and NACbetates genes,
      suggesting an involvement of DINE-1 elements in duplication and amplification of
      these genes.

PMID- 22649556
TI  - Topiramate-induced modulation of hepatic molecular mechanisms: an aspect for its
      anti-insulin resistant effect.
AB  - Topiramate is an antiepileptic drug known to ameliorate insulin resistance
      besides reducing body weight. Albeit liver plays a fundamental role in regulation
      of overall insulin resistance, yet the effect of topiramate on this organ is
      controversial and is not fully investigated. The current work aimed to study the
      potential hepatic molecular mechanistic cassette of the anti-insulin resistance
      effect of topiramate. To this end, male Wistar rats were fed high fat/high
      fructose diet (HFFD) for 10 weeks to induce obese, insulin resistant,
      hyperglycemic animals, but with no overt diabetes. Two HFFD-groups received oral
      topiramate, 40 or 100 mg/kg, for two weeks. Topiramate, on the hepatic molecular
      level, has opposed the high fat/high fructose diet effect, where it significantly
      increased adiponectin receptors, GLUT2, and tyrosine kinase activity, while
      decreased insulin receptor isoforms. Besides, it improved the altered glucose
      homeostasis and lipid profile, lowered the ALT level, caused subtle, yet
      significant decrease in TNF-alpha, and boosted adiponectin in a dose dependent
      manner. Moreover, topiramate decreased liver weight/, visceral fat weight/, and
      epididymal fat weight/body weight ratios. The study proved that insulin
      resistance has an effect on hepatic molecular level and that the topiramate
      mediated insulin sensitivity is ensued partly by modulation of hepatic insulin
      receptor isoforms, activation of tyrosine kinase, induction of GLUT2 and
      elevation of adiponectin receptors, as well as their ligand, adiponectin, besides
      its known improving effect on glucose tolerance and lipid homeostasis.

PMID- 22649557
TI  - NKT cells stimulated by long fatty acyl chain sulfatides significantly reduce the
      incidence of type 1 diabetes in nonobese diabetic mice [corrected].
AB  - Sulfatide-reactive type II NKT cells have been shown to regulate autoimmunity and
      anti-tumor immunity. Although, two major isoforms of sulfatide, C16:0 and C24:0,
      are enriched in the pancreas, their relative role in autoimmune diabetes is not
      known. Here, we report that sulfatide/CD1d-tetramer(+) cells accumulate in the
      draining pancreatic lymph nodes, and that treatment of NOD mice with sulfatide or
      C24:0 was more efficient than C16:0 in stimulating the NKT cell-mediated transfer
      of a delay in onset from T1D into NOD.Scid recipients. Using NOD.CD1d(-/-) mice,
      we show that this delay of T1D is CD1d-dependent. Interestingly, the latter delay
      or protection from T1D is associated with the enhanced secretion of IL-10 rather
      than IFN-g by C24:0-treated CD4(+) T cells and the deviation of the islet
      reactive diabetogenic T cell response. Both C16:0 and C24:0 sulfatide isoforms
      are unable to activate and expand type I iNKT cells. Collectively, these data
      suggest that C24:0 stimulated type II NKT cells may regulate protection from T1D
      by activating DCs to secrete IL-10 and suppress the activation and expansion of
      type I iNKT cells and diabetogenic T cells. Our results raise the possibility
      that C24:0 may be used therapeutically to delay the onset and protect from T1D in
      humans.

PMID- 22649558
TI  - Dopamine inactivation efficacy related to functional DAT1 and COMT variants
      influences motor response evaluation.
AB  - BACKGROUND: Dopamine plays an important role in orienting, response anticipation
      and movement evaluation. Thus, we examined the influence of functional variants
      related to dopamine inactivation in the dopamine transporter (DAT1) and catechol
      O-methyltransferase genes (COMT) on the time-course of motor processing in a
      contingent negative variation (CNV) task. METHODS: 64-channel EEG recordings were
      obtained from 195 healthy adolescents of a community-based sample during a
      continuous performance task (A-X version). Early and late CNV as well as motor
      postimperative negative variation were assessed. Adolescents were genotyped for
      the COMT Val(158)Met and two DAT1 polymorphisms (variable number tandem repeats
      in the 3'-untranslated region and in intron 8). RESULTS: The results revealed a
      significant interaction between COMT and DAT1, indicating that COMT exerted
      stronger effects on lateralized motor post-processing (centro-parietal motor
      postimperative negative variation) in homozygous carriers of a DAT1 haplotype
      increasing DAT1 expression. Source analysis showed that the time interval 500
      1000 ms after the motor response was specifically affected in contrast to
      preceding movement anticipation and programming stages, which were not altered.
      CONCLUSIONS: Motor slow negative waves allow the genomic imaging of dopamine
      inactivation effects on cortical motor post-processing during response
      evaluation. This is the first report to point towards epistatic effects in the
      motor system during response evaluation, i.e. during the post-processing of an
      already executed movement rather than during movement programming.

PMID- 22649559
TI  - Rgnef (p190RhoGEF) knockout inhibits RhoA activity, focal adhesion establishment,
      and cell motility downstream of integrins.
AB  - BACKGROUND: Cell migration is a highly regulated process that involves the
      formation and turnover of cell-matrix contact sites termed focal adhesions. Rho
      family GTPases are molecular switches that regulate actin and focal adhesion
      dynamics in cells. Guanine nucleotide exchange factors (GEFs) activate Rho-family
      GTPases. Rgnef (p190RhoGEF) is a ubiquitous 190 kDa GEF implicated in the control
      of colon carcinoma and fibroblast cell motility. PRINCIPAL FINDINGS: Rgnef exon
      24 floxed mice (Rgnef(flox)) were created and crossed with cytomegalovirus (CMV)
      driven Cre recombinase transgenic mice to inactivate Rgnef expression in all
      tissues during early development. Heterozygous Rgnef(WT/flox) (Cre+) crosses
      yielded normal Mendelian ratios at embryonic day 13.5, but Rgnef(flox/flox)
      (Cre+) mice numbers at 3 weeks of age were significantly less than expected.
      Rgnef(flox/flox) (Cre+) (Rgnef-/-) embryos and primary mouse embryo fibroblasts
      (MEFs) were isolated and verified to lack Rgnef protein expression. When compared
      to wildtype (WT) littermate MEFs, loss of Rgnef significantly inhibited
      haptotaxis migration, wound closure motility, focal adhesion number, and RhoA
      GTPase activation after fibronectin-integrin stimulation. In WT MEFs, Rgnef
      activation occurs within 60 minutes upon fibronectin plating of cells associated
      with RhoA activation. Rgnef-/- MEF phenotypes were rescued by epitope-tagged
      Rgnef re-expression. CONCLUSIONS: Rgnef-/- MEF phenotypes were due to Rgnef loss
      and support an essential role for Rgnef in RhoA regulation downstream of
      integrins in control of cell migration.

PMID- 22649560
TI  - A putative transcription factor MYT2 regulates perithecium size in the ascomycete
      Gibberella zeae.
AB  - The homothallic ascomycete fungus Gibberella zeae is a plant pathogen that is
      found worldwide, causing Fusarium head blight (FHB) in cereal crops and ear rot
      of maize. Ascospores formed in fruiting bodies (i.e., perithecia) are
      hypothesized to be the primary inocula for FHB disease. Perithecium development
      is a complex cellular differentiation process controlled by many developmentally
      regulated genes. In this study, we selected a previously reported putative
      transcription factor containing the Myb DNA-binding domain MYT2 for an in-depth
      study on sexual development. The deletion of MYT2 resulted in a larger
      perithecium, while its overexpression resulted in a smaller perithecium when
      compared to the wild-type strain. These data suggest that MYT2 regulates
      perithecium size differentiation. MYT2 overexpression affected pleiotropic
      phenotypes including vegetative growth, conidia production, virulence, and
      mycotoxin production. Nuclear localization of the MYT2 protein supports its role
      as a transcriptional regulator. Transcriptional analyses of trichothecene
      synthetic genes suggest that MYT2 additionally functions as a suppressor for
      trichothecene production. This is the first study characterizing a transcription
      factor required for perithecium size differentiation in G. zeae, and it provides
      a novel angle for understanding sexual development in filamentous fungi.

PMID- 22649561
TI  - Betaine and secondary events in an acute coronary syndrome cohort.
AB  - BACKGROUND: Betaine insufficiency is associated with unfavourable vascular risk
      profiles in metabolic syndrome patients. We investigated associations between
      betaine insufficiency and secondary events in acute coronary syndrome patients.
      METHODS: Plasma (531) and urine (415) samples were collected four months after
      discharge following an acute coronary event. Death (34), secondary acute
      myocardial infarction (MI) (70) and hospital admission for heart failure (45)
      events were recorded over a median follow-up of 832 days. PRINCIPAL FINDINGS: The
      highest and lowest quintiles of urinary betaine excretion associated with risk of
      heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with
      subsequent acute MI. The lowest quintile of plasma betaine was associated with
      subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart
      failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile
      plasma concentrations of dimethylglycine (betaine metabolite) and top quintile
      plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004,
      <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High
      homocysteine was associated with high or low betaine excretion in >60% of these
      subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle
      quintile of plasma betaine concentration (p = 0.002). CONCLUSIONS: Betaine
      insufficiency indicates increased risk of secondary heart failure and acute MI.
      Its association with elevated homocysteine may partly explain the disappointing
      results of folate supplementation. In some patients, especially with diabetes,
      elevated plasma betaine also indicates increased risk.

PMID- 22649562
TI  - Macromolecular crowding directs extracellular matrix organization and mesenchymal
      stem cell behavior.
AB  - Microenvironments of biological cells are dominated in vivo by macromolecular
      crowding and resultant excluded volume effects. This feature is absent in dilute
      in vitro cell culture. Here, we induced macromolecular crowding in vitro by using
      synthetic macromolecular globules of nm-scale radius at physiological levels of
      fractional volume occupancy. We quantified the impact of induced crowding on the
      extracellular and intracellular protein organization of human mesenchymal stem
      cells (MSCs) via immunocytochemistry, atomic force microscopy (AFM), and AFM
      enabled nanoindentation. Macromolecular crowding in extracellular culture media
      directly induced supramolecular assembly and alignment of extracellular matrix
      proteins deposited by cells, which in turn increased alignment of the
      intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further
      affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular
      crowding can thus aid the design of more physiologically relevant in vitro
      studies and devices for MSCs and other cells, by increasing the fidelity between
      materials synthesized by cells in vivo and in vitro.

PMID- 22649563
TI  - Effects of kisspeptin1 on electrical activity of an extrahypothalamic population
      of gonadotropin-releasing hormone neurons in medaka (Oryzias latipes).
AB  - Kisspeptin (product of the kiss1 gene) is the most potent known activator of the
      hypothalamo-pituitary-gonadal axis. Both kiss1 and the kisspeptin receptor are
      highly expressed in the hypothalamus of vertebrates, and low doses of kisspeptin
      have a robust and long-lasting stimulatory effect on the rate of action potential
      firing of hypophysiotropic gonadotropin releasing hormone-1 (GnRH1) neurons in
      mice. Fish have multiple populations of GnRH neurons distinguished by their
      location in the brain and the GnRH gene that they express. GnRH3 neurons located
      in the terminal nerve (TN) associated with the olfactory bulb are neuromodulatory
      and do not play a direct role in regulating pituitary-gonadal function. In medaka
      fish, the electrical activity of TN-GnRH3 neurons is modulated by visual cues
      from conspecifics, and is thought to act as a transmitter of information from the
      external environment to the central nervous system. TN-GnRH3 neurons also play a
      role in sexual motivation and arousal states, making them an important population
      of neurons to study for understanding coordination of complex behaviors. We
      investigated the role of kisspeptin in regulating electrical activity of TN-GnRH3
      neurons in adult medaka. Using electrophysiology in an intact brain preparation,
      we show that a relatively brief treatment with 100 nM of kisspeptin had a long
      lasting stimulatory effect on the electrical activity of an extrahypothalamic
      population of GnRH neurons. Dose-response analysis suggests a relatively narrow
      activational range of this neuropeptide. Further, blocking action potential
      firing with tetrodotoxin and blocking synaptic transmission with a low
      Ca(2+)/high Mg(2+) solution inhibited the stimulatory action of kisspeptin on
      electrical activity, indicating that kisspeptin is acting indirectly through
      synaptic regulation to excite TN-GnRH3 neurons. Our findings provide a new
      perspective on kisspeptin's broader functions within the central nervous system,
      through its regulation of an extrahypothalamic population of GnRH neurons
      involved in multiple neuromodulatory functions.

PMID- 22649564
TI  - Toward a mechanistic modeling of nitrogen limitation on vegetation dynamics.
AB  - Nitrogen is a dominant regulator of vegetation dynamics, net primary production,
      and terrestrial carbon cycles; however, most ecosystem models use a rather
      simplistic relationship between leaf nitrogen content and photosynthetic
      capacity. Such an approach does not consider how patterns of nitrogen allocation
      may change with differences in light intensity, growing-season temperature and
      CO(2) concentration. To account for this known variability in nitrogen
      photosynthesis relationships, we develop a mechanistic nitrogen allocation model
      based on a trade-off of nitrogen allocated between growth and storage, and an
      optimization of nitrogen allocated among light capture, electron transport,
      carboxylation, and respiration. The developed model is able to predict the
      acclimation of photosynthetic capacity to changes in CO(2) concentration,
      temperature, and radiation when evaluated against published data of V(c,max)
      (maximum carboxylation rate) and J(max) (maximum electron transport rate). A
      sensitivity analysis of the model for herbaceous plants, deciduous and evergreen
      trees implies that elevated CO(2) concentrations lead to lower allocation of
      nitrogen to carboxylation but higher allocation to storage. Higher growing-season
      temperatures cause lower allocation of nitrogen to carboxylation, due to higher
      nitrogen requirements for light capture pigments and for storage. Lower levels of
      radiation have a much stronger effect on allocation of nitrogen to carboxylation
      for herbaceous plants than for trees, resulting from higher nitrogen requirements
      for light capture for herbaceous plants. As far as we know, this is the first
      model of complete nitrogen allocation that simultaneously considers nitrogen
      allocation to light capture, electron transport, carboxylation, respiration and
      storage, and the responses of each to altered environmental conditions. We expect
      this model could potentially improve our confidence in simulations of carbon
      nitrogen interactions and the vegetation feedbacks to climate in Earth system
      models.

PMID- 22649565
TI  - Field and laboratory studies provide insights into the meaning of day-time
      activity in a subterranean rodent (Ctenomys aff. knighti), the tuco-tuco.
AB  - South American subterranean rodents (Ctenomys aff. knighti), commonly known as
      tuco-tucos, display nocturnal, wheel-running behavior under light-dark (LD)
      conditions, and free-running periods >24 h in constant darkness (DD). However,
      several reports in the field suggested that a substantial amount of activity
      occurs during daylight hours, leading us to question whether circadian
      entrainment in the laboratory accurately reflects behavior in natural conditions.
      We compared circadian patterns of locomotor activity in DD of animals previously
      entrained to full laboratory LD cycles (LD12:12) with those of animals that were
      trapped directly from the field. In both cases, activity onsets in DD immediately
      reflected the previous dark onset or sundown. Furthermore, freerunning periods
      upon release into DD were close to 24 h indicating aftereffects of prior
      entrainment, similarly in both conditions. No difference was detected in the
      phase of activity measured with and without access to a running wheel. However,
      when individuals were observed continuously during daylight hours in a semi
      natural enclosure, they emerged above-ground on a daily basis. These day-time
      activities consisted of foraging and burrow maintenance, suggesting that the
      designation of this species as nocturnal might be inaccurate in the field. Our
      study of a solitary subterranean species suggests that the circadian clock is
      entrained similarly under field and laboratory conditions and that day-time
      activity expressed only in the field is required for foraging and may not be time
      dictated by the circadian pacemaker.

PMID- 22649566
TI  - Impaired heat shock response in cells expressing full-length polyglutamine
      expanded huntingtin.
AB  - The molecular mechanisms by which polyglutamine (polyQ)-expanded huntingtin (Htt)
      causes neurodegeneration in Huntington's disease (HD) remain unclear. The
      malfunction of cellular proteostasis has been suggested as central in HD
      pathogenesis and also as a target of therapeutic interventions for the treatment
      of HD. We present results that offer a previously unexplored perspective
      regarding impaired proteostasis in HD. We find that, under non-stress conditions,
      the proteostatic capacity of cells expressing full length polyQ-expanded Htt is
      adequate. Yet, under stress conditions, the presence of polyQ-expanded Htt
      impairs the heat shock response, a key component of cellular proteostasis. This
      impaired heat shock response results in a reduced capacity to withstand the
      damage caused by cellular stress. We demonstrate that in cells expressing polyQ
      expanded Htt the levels of heat shock transcription factor 1 (HSF1) are reduced,
      and, as a consequence, these cells have an impaired a heat shock response. Also,
      we found reduced HSF1 and HSP70 levels in the striata of HD knock-in mice when
      compared to wild-type mice. Our results suggests that full length, non-aggregated
      polyQ-expanded Htt blocks the effective induction of the heat shock response
      under stress conditions and may thus trigger the accumulation of cellular damage
      during the course of HD pathogenesis.

PMID- 22649567
TI  - Patients with inflammatory bowel disease exhibit dysregulated responses to
      microbial DNA.
AB  - BACKGROUND: A critical role for the gut epithelium lies in its ability to
      discriminate between pathogens and commensals and respond appropriately.
      Dysfunctional interactions between microbes and epithelia are believed to have a
      role in inflammatory bowel disease (IBD). In this study, we analyzed microbiota
      and gene expression in IBD patients and examined responses of mucosal biopsies to
      bacterial DNA. METHODS: Biopsies were taken from non-inflamed areas of the colon
      in healthy controls (HC) and Crohn's disease (CD) and ulcerative colitis (UC)
      patients in remission. Biopsies were snap-frozen or cultured with DNA from
      Lactobacillus plantarum (LP) or Salmonella dublin (SD). Gene expression was
      analyzed under basal conditions and in response to DNA. Gene networks were
      analyzed using Ingenuity Pathways software. Mucosal-associated microbiota was
      analyzed using terminal restriction fragment length polymorphism. Frequency of
      single nucleotide polymorphisms in NOD2 and TLR9 was assessed. RESULTS: Patients
      with IBD had altered microbiota, enhanced expression of inflammatory genes, and
      increased correlations between specific gene expression and microbes. Principle
      component analysis showed CD and UC patients to cluster independently from
      healthy controls in both gene expression and microbial analysis. DNA from LP
      stimulated anti-inflammatory pathways in controls and UC patients, but induced an
      upregulation of IL17A in CD patients. There were no differences in SNP
      frequencies of TLR9 or NOD2 in the groups. CONCLUSIONS: Patients with Crohn's
      disease exhibit altered responses to bacterial DNA. These findings suggest that
      the gut response to bacterial DNA may depend not only on the specific type of
      bacterial DNA, but also on the host.

PMID- 22649568
TI  - Propentofylline targets TROY, a novel microglial signaling pathway.
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive primary brain
      cancer, with a median survival of less than 2 years after diagnosis with current
      available therapies. The tumor microenvironment serves a critical role in tumor
      invasion and progression, with microglia as a critical player. Our laboratory has
      previously demonstrated that propentofylline, an atypical methylxanthine with
      central nervous system glial modulating and anti-inflammatory actions,
      significantly decreases tumor growth in a GBM rodent model by preferentially
      targeting microglia. In the present study, we used the CNS-1 rat glioma model to
      elucidate the mechanisms of propentofylline. Here we demonstrate that
      propentofylline targets TROY, a novel signaling molecule up-regulated in
      infiltrating microglia, and not macrophages, in response to CNS-1 cells. We
      identify Pyk2, Rac1 and pJNK as the downstream signaling molecules of TROY
      through western blot analysis and siRNA transfection. We demonstrate that
      inhibition of TROY expression in microglia by siRNA transfection significantly
      inhibits microglial migration towards CNS-1 cells similar to 10 uM
      propentofylline treatment. These results identify TROY as a novel molecule
      expressed in microglia, involved in their migration and targeted by
      propentofylline. Furthermore, these results describe a signaling molecule that is
      differentially expressed between microglia and macrophages in the tumor
      microenvironment.

PMID- 22649569
TI  - Impact of isoniazid resistance-conferring mutations on the clinical presentation
      of isoniazid monoresistant tuberculosis.
AB  - BACKGROUND: Specific isoniazid (INH) resistance conferring mutations have been
      shown to impact the likelihood of tuberculosis (TB) transmission. However, their
      role in the clinical presentation and outcomes of TB has not been evaluated.
      METHODS: We included all cases of culture-confirmed, INH monoresistant
      tuberculosis reported to the San Francisco Department of Public Health
      Tuberculosis Control Section from October 1992 through October 2005. For cases
      with stored culture isolates, we used polymerase chain reaction (PCR) testing and
      gene sequencing to identify INH resistance-conferring mutations, and compared
      genotypic and phenotypic characteristics. RESULTS: Among 101 consecutive cases of
      INH monoresistant TB in San Francisco 19 (19%) had isolates with a katG mutation
      other than S315T; 38 (38%) had isolates with the katG S315T mutation, 29 (29%)
      had isolates with a inhA-15;c-t promoter mutation, and 15 (15%) had isolates with
      other mutations. The katG S315T mutation was independently associated with high
      level INH resistance (risk ratio [RR] 1.56, 95% confidence interval [CI] 1.07
      2.27), and the inhA-15;c-t promoter mutation was inversely associated with high
      level INH resistance (RR 0.43, 95% CI 0.21-0.89). However, specific INH
      resistance-conferring mutations were not associated with the clinical severity or
      outcomes of INH monoresistant TB cases. CONCLUSION: These data suggest that INH
      resistance-conferring mutations do not impact the clinical presentation of TB.

PMID- 22649570
TI  - Activated iNKT cells promote memory CD8+ T cell differentiation during viral
      infection.
AB  - alpha-Galactosylceramide (alpha-GalCer) is the prototypical lipid ligand for
      invariant NKT cells. Recent studies have proposed that alpha-GalCer is an
      effective adjuvant in vaccination against a range of immune challenges, however
      its mechanism of action has not been completely elucidated. A variety of delivery
      methods have been examined including pulsing dendritic cells with alpha-GalCer to
      optimize the potential of alpha-GalCer. These methods are currently being used in
      a variety of clinical trials in patients with advanced cancer but cannot be used
      in the context of vaccine development against pathogens due to their complexity.
      Using a simple delivery method, we evaluated alpha-GalCer adjuvant properties,
      using the mouse model for cytomegalovirus (MCMV). We measured several key
      parameters of the immune response to MCMV, including inflammation, effector, and
      central memory CD8(+) T cell responses. We found that alpha-GalCer injection at
      the time of the infection decreases viral titers, alters the kinetics of the
      inflammatory response, and promotes both increased frequencies and numbers of
      virus-specific memory CD8(+) T cells. Overall, our data suggest that iNKT cell
      activation by alpha-GalCer promotes the development of long-term protective
      immunity through increased fitness of central memory CD8(+) T cells, as a
      consequence of reduced inflammation.

PMID- 22649571
TI  - Peroxisomes, oxidative stress, and inflammation.
AB  - Peroxisomes are intracellular organelles mediating a wide variety of biosynthetic
      and biodegradative reactions. Included among these are the metabolism of hydrogen
      peroxide and other reactive species, molecules whose levels help define the
      oxidative state of cells. Loss of oxidative equilibrium in cells of tissues and
      organs potentiates inflammatory responses which can ultimately trigger human
      disease. The goal of this article is to review evidence for connections between
      peroxisome function, oxidative stress, and inflammation in the context of human
      health and degenerative disease. Dysregulated points in this nexus are identified
      and potential remedial approaches are presented.

PMID- 22649573
TI  - An Introduction to the Volume 4, Number 2 of Behavior Analysis in Practice (BAP).

PMID- 22649572
TI  - Septin 8 is an interaction partner and in vitro substrate of MK5.
AB  - AIM: To identify novel substrates for the mitogen-activated protein kinase
      activated protein kinase 5 (MK5). METHODS: Yeast two-hybrid screening with MK5 as
      bait was used to identify novel possible interaction partners. The binding of
      putative partner was further examined by glutathione S-transferase (GST) pull
      down, co-immunoprecipitation and fluorescence resonance energy transfer (FRET)
      analysis. In vitro kinase and peptide array assays were used to map MK5
      phosphoacceptor sites on the new partner. Confocal microscopy was performed to
      study the subcellular localization of MK5 and its partners. RESULTS: Septin 8 was
      identified as a novel interaction partner for MK5 by yeast two-hybrid screening.
      This interaction was confirmed by GST pull-down, co-immunoprecipitation and FRET
      analysis. Septin 5, which can form a complex with septin 8, did not interact with
      MK5. Serine residues 242 and 271 on septin 8 were identified as in vitro MK5
      phosphorylation sites. MK5 and septin 8 co-localized in the perinuclear area and
      in cell protrusions. Moreover, both proteins co-localized with vesicle marker
      synaptophysin. CONCLUSION: Septin 8 is a bona fide interaction partner and in
      vitro substrate for MK5. This interaction may be implicated in vesicle
      trafficking.

PMID- 22649574
TI  - Defusion: a behavior-analytic strategy for addressing private events.
AB  - Applied behavior analysts encounter situations in which private events hinder
      client progress, and additional techniques to address these issues are needed. By
      conceptualizing private events as verbal rules, we provide a behavior-analytic
      framework for understanding and addressing these events. Relational frame theory
      (RFT) is the basis for this conceptual foundation; the empirically based
      principles of RFT are presented along with direct implications for understanding
      private events. Defusion, an RFT-based technique for addressing private events,
      is then described and empirical studies that evaluate the effects of defusion are
      reviewed. Finally, potential clinical applications for practicing behavior
      analysts are offered.

PMID- 22649575
TI  - The matching law: a tutorial for practitioners.
AB  - The application of the matching law has historically been limited to use as a
      quantitative measurement tool in the experimental analysis of behavior to
      describe temporally extended patterns of behavior-environment relations. In
      recent years, however, applications of the matching law have been translated to
      clinical settings and populations to gain a better understanding of how naturally
      occurring events affect socially important behaviors. This tutorial provides a
      brief background of the conceptual foundations of matching, an overview of the
      various matching equations that have been used in research, and a description of
      how to interpret the data derived from these equations in the context of numerous
      examples of matching analyses conducted with socially important behavior. An
      appendix of resources is provided to direct readers to primary sources, as well
      as useful articles and books on the topic.

PMID- 22649576
TI  - Using taped-problems and rewards to increase addition-fact fluency in a first
      grade general education classroom.
AB  - We used a multiple baseline design across math facts to evaluate classwide use of
      a taped problem (TP) intervention on first graders' digits correct per minute in
      a general education classroom. During TP, students attempted to respond to each
      math fact before they heard the answer on an audiotape. As problems were
      repeated, response intervals were varied and individual and group feedback and
      rewards were provided contingent upon improved performance. Across all 3 sets of
      problems, digits correct per minute increased following the use of TP. We discuss
      the efficacy of TP as an instructional (as opposed to remedial) procedure,
      practical implications for teachers, and areas for future research.

PMID- 22649577
TI  - Improving safe consumer transfers in a day treatment setting using training and
      feedback.
AB  - An intervention package that included employee training, supervisory feedback,
      and graphic feedback was developed to increase employees' safe patient-transfers
      at a day treatment center for adults with disabilities. The intervention was
      developed based on the center's results from a Performance Diagnostic Checklist
      (PDC), which focused on antecedents, equipment and processes, knowledge and
      skills, and consequences related to patient-transfers. A multiple baseline (MBL)
      across two lifts (pivot and trunk), with one lift (side) remaining in baseline
      was used to evaluate the effects of the treatment package on three lifts commonly
      used by three health-care workers. The results indicated a substantial increase
      in the overall safe performance of the three lifts. The mean increase for group
      safety performance following intervention was 34% and 29% over baseline measures
      for the two target transfers, and 28% over baseline measures for the nontargeted
      transfer. The implications of these findings suggest that in settings where
      patient transfers are frequent and injuries are likely to occur (e.g., hospitals,
      day treatment centers), safe lifting and transferring behaviors can improve with
      an efficient and cost-effective intervention.

PMID- 22649578
TI  - A microsoft excel((r)) 2010 based tool for calculating interobserver agreement.
AB  - This technical report provides detailed information on the rationale for using a
      common computer spreadsheet program (Microsoft Excel((r))) to calculate various
      forms of interobserver agreement for both continuous and discontinuous data sets.
      In addition, we provide a brief tutorial on how to use an Excel spreadsheet to
      automatically compute traditional total count, partial agreement-within
      intervals, exact agreement, trial-by-trial, interval-by-interval, scored
      interval, unscored-interval, total duration, and mean duration-per-interval
      interobserver agreement algorithms. We conclude with a discussion of how
      practitioners may integrate this tool into their clinical work.

PMID- 22649579
TI  - Reading groups: a practical means of enhancing professional knowledge among human
      service practitioners.
AB  - Quality human service provision is heavily dependent on practitioners maintaining
      up-to-date professional knowledge. We evaluated a monthly reading group process
      as a practical means of enhancing professional knowledge among educators in a
      program for adults with severe disabilities. The reading group process was
      designed to minimize disruptions to participants' direct contact time with
      students and to promote participant acceptance of the process. The process
      followed a structured format involving study questions and systematic prompting
      to ensure active participation. Comparison of pre- and post-quiz responses to
      short-answer and multiple-choice questions showed consistent improvement in
      correct answers following each of four reading group meetings. Survey responses
      indicated all participants reported the process to be highly acceptable. Results
      are discussed regarding guidelines for behavior analysts interested in enhancing
      professional knowledge of other practitioners with whom they work, with a focus
      on obtaining administrative approval for reading group activities, structuring
      the activities to promote active participation, and using strategies to enhance
      participant acceptance.

PMID- 22649580
TI  - Gerald L. "Jerry" shook: visionary for the profession of behavior analysis.

PMID- 22649581
TI  - Patterns of periodic holes created by increased cell motility.
AB  - The reaction and diffusion of morphogens is a mechanism widely used to explain
      many spatial patterns in physics, chemistry and developmental biology. However,
      because experimental control is limited in most biological systems, it is often
      unclear what mechanisms account for the biological patterns that arise. Here, we
      study a biological model of cultured vascular mesenchymal cells (VMCs), which
      normally self-organize into aggregates that form into labyrinthine
      configurations. We use an experimental control and a mathematical model that
      includes reacting and diffusing morphogens and a third variable reflecting local
      cell density. With direct measurements showing that cell motility was increased
      ninefold and threefold by inhibiting either Rho kinase or non-muscle myosin-II,
      respectively, our experimental results and mathematical modelling demonstrate
      that increased motility alters the multicellular pattern of the VMC cultures,
      from labyrinthine to a pattern of periodic holes. These results suggest
      implications for the tissue engineering of functional replacements for trabecular
      or spongy tissue such as endocardium and bone.

PMID- 22649582
TI  - The effect of the signalling scheme on the robustness of pattern formation in
      development.
AB  - Pattern formation in development is a complex process which involves spatially
      distributed signals called morphogens that influence gene expression and thus the
      phenotypic identity of cells. Usually different cell types are spatially
      segregated, and the boundary between them may be determined by a threshold value
      of some state variable. The question arises as to how sensitive the location of
      such a boundary is to variations in properties, such as parameter values, that
      characterize the system. Here, we analyse both deterministic and stochastic
      reaction-diffusion models of pattern formation with a view towards understanding
      how the signalling scheme used for patterning affects the variability of boundary
      determination between cell types in a developing tissue.

PMID- 22649583
TI  - A mechanical Turing machine: blueprint for a biomolecular computer.
AB  - We describe a working mechanical device that embodies the theoretical computing
      machine of Alan Turing, and as such is a universal programmable computer. The
      device operates on three-dimensional building blocks by applying mechanical
      analogues of polymer elongation, cleavage and ligation, movement along a polymer,
      and control by molecular recognition unleashing allosteric conformational
      changes. Logically, the device is not more complicated than biomolecular machines
      of the living cell, and all its operations are part of the standard repertoire of
      these machines; hence, a biomolecular embodiment of the device is not infeasible.
      If implemented, such a biomolecular device may operate in vivo, interacting with
      its biochemical environment in a program-controlled manner. In particular, it may
      'compute' synthetic biopolymers and release them into its environment in response
      to input from the environment, a capability that may have broad pharmaceutical
      and biological applications.

PMID- 22649584
TI  - Less haste, less waste: on recycling and its limits in strand displacement
      systems.
AB  - We study the potential for molecule recycling in chemical reaction systems and
      their DNA strand displacement realizations. Recycling happens when a product of
      one reaction is a reactant in a later reaction. Recycling has the benefits of
      reducing consumption, or waste, of molecules and of avoiding fuel depletion. We
      present a binary counter that recycles molecules efficiently while incurring just
      a moderate slowdown compared with alternative counters that do not recycle
      strands. This counter is an n-bit binary reflecting Gray code counter that
      advances through 2(n) states. In the strand displacement realization of this
      counter, the waste-total number of nucleotides of the DNA strands consumed-is
      polynomial in n, the number of bits of the counter, while the waste of
      alternative counters grows exponentially in n. We also show that our n-bit
      counter fails to work correctly when many (Theta(n)) copies of the species that
      represent the bits of the counter are present initially. The proof applies more
      generally to show that in chemical reaction systems where all but one reactant of
      each reaction are catalysts, computations longer than a polynomial function of
      the size of the system are not possible when there are polynomially many copies
      of the system present.

PMID- 22649585
TI  - Modern Technologies for Creating Synthetic Antibodies for Clinical application.
AB  - The modular structure and versatility of antibodies enables one to modify natural
      immunoglobulins in different ways for various clinical applications. Rational
      design and molecular engineering make it possible to directionally modify the
      molecular size, affinity, specificity, and immunogenicity and effector functions
      of an antibody, as well as to combine them with other functional agents. This
      review focuses on up-to-date methods of antibody engineering for diagnosing and
      treating various diseases, particularly on new technologies meant to refine the
      effector functions of therapeutic antibodies.

PMID- 22649588
TI  - Life and Death Decisions in the CD95 System: Main Pro-and Anti-Apoptotic
      Modulators.
AB  - Apoptosis is common to all multicellular organisms. Apoptosis can be triggered by
      the extrinsic (death receptor (DR)) or the intrinsic (mitochondrial) death
      pathways. CD95 (APO-1/Fas) is a prototypic member of the DR family. This review
      is focused on the mechanisms of CD95 (APO-1/Fas)-mediated apoptosis and the role
      in the apoptosis of the death effector domain (DED)-containing proteins: pro
      apoptotic protein procaspase-8 and anti-apoptotic protein c-FLIP. Gaining
      insights into these processes will improve our understanding of the pathogenesis
      of diseases such as cancer, autoimmunity and AIDS, and will open new approaches
      to rational treatment strategies.

PMID- 22649587
TI  - Catalytic bioscavengers against toxic esters, an alternative approach for
      prophylaxis and treatments of poisonings.
AB  - Bioscavengers are biopharmaceuticals that specifically react with toxicants.
      Thus, enzymes reacting with poisonous esters can be used as bioscavengers for
      neutralization of toxic molecules before they reach physiological targets.
      Parenteral administration of bioscavengers is, therefore, intended for
      prophylaxis or pre-treatments, emergency and post-exposure treatments of
      intoxications. These enzymes can also be used for application on skin, mucosa and
      wounds as active components of topical skin protectants and decontamination
      solutions. Human butyrylcholinesterase is the first stoichiometric bioscavenger
      for safe and efficient prophylaxis of organophosphate poisoning. However, huge
      amounts of a costly enzyme are needed for protection. Thus, the bioscavenger
      approach will be greatly improved by the use of catalytic bioscavengers.
      Catalytic bioscavengers are enzymes capable of degrading toxic esters with a
      turnover. Suitable catalytic bioscavengers are engineered mutants of human
      enzymes. Efficient mutants of human butyrylcholinesterase have been made that
      hydrolyze cocaine at a high rate. Mutants of human cholinesterases capable of
      hydrolyzing OPs have been made, but so far their activity is too low to be of
      medical interest. Human paraoxonase a promiscuous plasma enzyme is certainly the
      most promising phosphotriesterase. However, its biotechnology is still in its
      infancy. Other enzymes and proteins from blood and organs, and secondary
      biological targets of OPs and carbamates are potential bioscavengers, in
      particular serum albumin that reacts with OPs and self-reactivates. Lastly, non
      human enzymes, phosphotriesterases and oxidases from various bacterial and
      eukaryotic sources could be used for external use against OP poisoning and for
      internal use after modifications for immunological compatibility.

PMID- 22649590
TI  - The Interaction between the RNA-Dependent RNA-Polymerase of the Hepatitis Virus
      and RNA Matrices.

PMID- 22649589
TI  - Analysis of myelin basic protein fragmentation by proteasome.
AB  - The proteasome is a high molecular protein complex whose purpose is specific
      protein degradation in eukaryotic cells. One of the proteasome functions is to
      produce peptides, which will then be presented on the outer cell membrane using
      main histocompatibility complex (MHC) molecules of the first or second class.
      There are definite reasons to believe that proteasome directly takes part in the
      specific degradation of myelin basic protein (MBP), which make up to 30% of all
      proteins in the myelin sheath of neuronal axons. The details of the proteasomal
      degradation of MBP are still unclear. In this work, the features of specific MBP
      degradation by proteasome were studied.It was demonstrated that MBP (non
      ubiquitinated) is a good substrate for 20S and for the 26S proteasome. This is
      the first work on detecting the sites of MBP proteolysis by proteasome from
      brains of SJL/J/J and Balb/C mice's lines. Substantial differences in the
      degradation pattern of this neuroantigen were found, which could indicate the
      better presentation MBP parts on MHC molecules in the case of mice predisposed to
      the development of experimental autoimmune encephalomyelitis.

PMID- 22649591
TI  - Studying of Membrane Localization of Recombinant Potassium Channels in E.coli.
AB  - The effective expression of recombinant membrane proteins in E.coli depends upon
      the targeting and insertion of proteins into the cellular membrane, as well as on
      those proteins adopting the correct spatial structure. A significant
      technological problem involves the design of approaches for detecting the
      location of target proteins within a host cell. Using a hybrid potassium channel
      KcsA-Kv1.3 as a model, we developed a technological scheme which is suitable for
      the study of membrane localization in E.coli cells of recombinant proteins
      containing voltage-gated eukaryotic potassium channels as the functional active
      site. The scheme involves both biochemical and fluorescent methods for detecting
      target proteins in the cytoplasmic membrane of E.coli, as well as the study of
      the ligand-binding activity of membrane-embedded proteins.

PMID- 22649586
TI  - The regulation of telomerase in oncogenesis.
AB  - The influence that the expression of the human (glial-derived neurotrophic factor
      (GDNF)) neurotrophic factor has on the morphology and proliferative activity of
      embryonic stem cells (SC) of a mouse with R1 lineage, as well as their ability to
      form embroid bodies (EB), has been studied. Before that, using a PCR (polymerase
      chain reaction) coupled with reverse transcription, it was shown that, in this
      very lineage of the embryonic SC, the expression of the receptors' genes is being
      fulfilled for the neurotropfic RET and GFRalpha1 glia factor. The mouse's
      embryonic SC lineage has been obtained, transfected by the human GDNF gene, and
      has been fused with the "green" fluorescent protein (GFP) gene. The presence of
      the expression of the human GDNF gene in the cells was shown by northern
      hybridization and the synthesis of its albuminous product by immunocitochemical
      coloration with the use of specific antibodies. The reliable slowing-down of the
      embriod-body formation by the embryonic SC transfected by the GDNF gene has been
      shown. No significant influence of the expression of the GDNF gene on the
      morphology and the proliferative activity of the transfected embryonic SCs has
      been found when compared with the control ones.

PMID- 22649592
TI  - Cell-free Production of the Extracellular Domain of the Nicotinic Acetylcholine
      Receptor.

PMID- 22649593
TI  - Complete Sequencing of the Mitochondrial Genome of Opisthorchis felineus,
      Causative Agent of Opisthorchiasis.
AB  - Opisthorchis felineus, a hepatic trematode, is the causative agent of
      opisthorchiasis, a dangerous disease in both human beings and animals.
      Opisthorchiasis is widespread in Russia, especially Western Siberia. The purpose
      of the present study was to determine the complete mitochondrial DNA sequence of
      this flatworm. Two parallel methods were employed: (1) capillary electrophoresis
      to sequence the mitochondrial genome fragments obtained through specific PCR
      amplification, and (2) high throughput sequencing of the DNA sample. Both methods
      made possible the determination of the complete nucleotide sequence of the O.
      felineus mitochondrial genome. The genome consists of a ring molecule 14,277 nt
      in length that contains 35 genes coding 2 rRNA, 22 tRNA, and 12 proteins: 3
      subunits of cytochrome-C-oxidase, 7 subunits of NADH-dehydrogenase, B
      apocytochrome, and subunit 6 of ATP-synthetase.Like many other flatworms, O.
      felineus is characterized by the absence of the ATP-synthetase subunit 8 gene.
      Nineteen out of the 22 tRNAs have a typical "clover leaf" structure. The
      tRNA(AGC) and tRNA-Cys genes lack DHU-loops, while the tRNA-Ser(UCA) has 2
      alternative structures: one with a DHU-loop, and one without it. Analyzing the
      results obtained from the high throughput sequencing revealed 45 single
      nucleotide polymorphisms within the mitochondrial genome. The results obtained in
      this study may be used in the development of molecular diagnostic methods for
      opisthorchiasis. This study shows that high throughput sequencing is a fast and
      effective method for decoding the mitochondrial genome of animals.

PMID- 22649594
TI  - The organization in micro-loops of an extended fragment of chicken chromosome 14,
      including the alpha globin gene cluster in the erythroid cells.
AB  - It has been shown that the activation of tissue-specific gene transcription
      during the course of cell differentiation is associated with a spatial
      reorganization of the genomic domains harboring those specific genes. This
      reorganization consists of the relocation to the nuclear matrix of the whole
      genomic domain containing one or more of the genes being transcribed. However, it
      remains unclear whether, during this process, extended areas of the genome also
      become attached to the nuclear matrix. We studied the genome's pattern of
      interaction with the nuclear matrix in both erythroid and non-erythroid cells of
      chickens, using a 220Kb region of chromosome #14, which contains the alpha-globin
      gene cluster and some surrounding house-keeping genes. The results show that in
      erythroid cells, the fragment of the genome containing the alpha-globin gene
      domain became spatially arranged into micro-loops which could not be detected by
      mapping experiments.

PMID- 22649595
TI  - The Production and Characteristics of a Mouse's Embryonic Stem Cell Lineage,
      Transfected by the Glia Neurotrophic Factor and Gene Fused with the Green
      Fluorescent Protein Gene.
AB  - The influence that the expression of the human (glial-derived neurotrophic factor
      (GDNF)) neurotrophic factor has on the morphology and proliferative activity of
      embryonic stem cells (SC) of a mouse with R1 lineage, as well as their ability to
      form embroid bodies (EB), has been studied. Before that, using a PCR (polymerase
      chain reaction) coupled with reverse transcription, it was shown that, in this
      very lineage of the embryonic SC, the expression of the receptors' genes is being
      fulfilled for the neurotropfic RET and GFRalpha1 glia factor. The mouse's
      embryonic SC lineage has been obtained, transfected by the human GDNF gene, and
      has been fused with the "green" fluorescent protein (GFP) gene. The presence of
      the expression of the human GDNF gene in the cells was shown by northern
      hybridization and the synthesis of its albuminous product by immunocitochemical
      coloration with the use of specific antibodies. The reliable slowing-down of the
      embriod-body formation by the embryonic SC transfected by the GDNF gene has been
      shown. No significant influence of the expression of the GDNF gene on the
      morphology and the proliferative activity of the transfected embryonic SCs has
      been found when compared with the control ones.

PMID- 22649596
TI  - Direct Matrix-Assisted Laser Desorption-Ionisation (MALDI) Mass-Spectrometry
      Bacteria Profiling for Identifying and Characterizing Pathogens.
AB  - This study examines the features and limitations of direct Matrix-Assisted Laser
      Desorption-Ionisation (MALDI) mass-spectrometry profiling of bacterial cells for
      investigating a microbial population. The optimal laboratory protocol, including
      crude bacteria lyses by a solution of 50% acetonitrile, 2.5% trifluoroacetic
      acid, and using alpha-cyano-4-hydroxy cinnamic acid as the MALDI matrix, has been
      developed. Two different bacteria species were under investigation, and
      representative mass spectra from 278 strains of Neisseria gonorrhoeae and 22
      strains of Helicobacter pylori have been analyzed. It's known that both bacteria
      demonstrate a variable degree of polymorphism. For N. gonorrhoeae, the MALDI mass
      spectra that was collected possessed about 70 peaks, 20 of which were good
      reproducible ones. In spite of the fact that three peaks were found with
      differing spectra in some strains, little diversity in the N. gonorrhoeae
      population was revealed. This fact indicates the prospects in using direct MALDI
      mass-spectrometry profiling for gonococcus identification. In the case of H.
      pylori strains, the variety in the collected mass-spectra was shown to be
      essential. Only five peaks were present in more than 70% of strains, and a single
      mass value was common for all spectra. While these data call into question the
      possibility of the reliable species identification of H. pylori using this
      approach, the intraspecies differentiation of strains was offered. Good
      association between MALDI profile distributions and the region of strain
      isolation have been found. Thus, the suggested direct MALDI mass-spectrometry
      profiling strategy, coupled with special analysis software, seems promising for
      the species identification of N. gonorrhoeae but is assumed insufficient for H.
      pylori species determination. At the same time, this would create a very good
      chance for an epidemiological study of such variable bacteria as H. pylori.

PMID- 22649597
TI  - The genes of antimicrobial peptides for the therapy of intracellular infections.

PMID- 22649598
TI  - The role of stacking interactions in complexes of proteins with adenine and
      Guanine fragments of ligands.

PMID- 22649599
TI  - Marine natural products: a way to new drugs.
AB  - The investigation of marine natural products (low molecular weight bioregulators)
      is a rapidly developing scientific field at the intersection of biology and
      chemistry. Investigations aimed at detecting, identifying, and understanding the
      structure of marine natural products have led to the discovery of 20,000 new
      substances, including those characterized by an extremely high physiological
      activity. Some results and prospects of works aimed at creating new drugs on the
      basis of marine natural products are discussed herein.

PMID- 22649600
TI  - Influenza virus neuraminidase: structure and function.
AB  - The structure of the influenza virus neuraminidases, the spatial organization of
      their active site, the mechanism of carbohydrate chains desialylation by
      neuraminidase, and its role in the influenza virus function at different stages
      of the viral infectious cycle are considered in this review. Data on the
      neuraminidase substrate specificity and different approaches in studying the
      activity of this enzyme are summarized. In addition, data on neuraminidase
      inhibitors (as antivirals) are provided, along with considerations on the
      mechanisms of resistance of modern influenza viruses to those antivirals.

PMID- 22649601
TI  - Computer modeling of the structure and spectra of fluorescent proteins.
AB  - Fluorescent proteins from the family of green fluorescent proteins are
      intensively used as biomarkers in living systems. The chromophore group based on
      the hydroxybenzylidene-imidazoline molecule, which is formed in nature from three
      amino-acid residues inside the protein globule and well shielded from external
      media, is responsible for light absorption and fluorescence. Along with the
      intense experimental studies of the properties of fluorescent proteins and their
      chromophores by biochemical, X-ray, and spectroscopic tools, in recent years,
      computer modeling has been used to characterize their properties and spectra. We
      present in this review the most interesting results of the molecular modeling of
      the structural parameters and optical and vibrational spectra of the
      chromophorecontaining domains of fluorescent proteins by methods of quantum
      chemistry, molecular dynamics, and combined quantum-mechanical-molecular
      mechanical approaches. The main emphasis is on the correlation of theoretical and
      experimental data and on the predictive power of modeling, which may be useful
      for creating new, efficient biomarkers.

PMID- 22649603
TI  - Self-renewal of stem cells.
AB  - Asymmetric division is one of the most fundamental characteristics of adult stem
      cells , which ensures one daughter cell maintains stem cell status and the other
      daughter cell becomes committed to differentiation. New data emerged recently
      that allow us to conclude that asymmetric division has another important aspect:
      it enables self-maintenance of stem cells.

PMID- 22649606
TI  - Relative Comparison of Catalytic Characteristics of Human Foamy Virus and HIV-1
      Integrases.
AB  - Due to their ability to integrate into the host cell's genome, retroviruses
      represent an optimal basis for the creation of gene therapy vectors. The
      integration reaction is carried out by a viral enzyme integrase: thus, a detailed
      research of this enzyme is required. In this work, the catalytic properties of
      human foamy virus integrase were studied. This virus belongs to the Retroviridae
      family. The dissociation constant was determined, together with the kinetics of
      integrase catalytic activity. The data obtained were compared to those for the
      human immunodeficiency virus integrase and a considerable similarity in the
      activity of the two enzymes was observed.

PMID- 22649605
TI  - M. tuberculosis Gene Expression during Transition to the "Non-Culturable" State.
AB  - We analyzed the gene expression profile under specific conditions during
      reversible transition of M. tuberculosis cells to the "non-culturable" (NC) state
      in a prolonged stationary phase. More than 500 genes were differentially
      regulated, while 238 genes were upregulated over all time points during NC cell
      formation. Approximately a quarter of these upregulated genes belong to insertion
      and phage sequences indicating a possible high intensity of genome modification
      processes taking place under transition to the NC state. Besides the high
      proportion of hypothetical/conserved hypothetical genes in the cohort of
      upregulated genes, there was a significant number of genes belonging to
      intermediary metabolism, respiration, information pathways, cell wall and cell
      processes, and genes encoding regulatory proteins. We conclude that NC cell
      formation is an active process involved in the regulation of many genes of
      different pathways. A more detailed analysis of the experimental data will help
      to understand the precise molecular mechanisms of dormancy/latency/persistence of
      M. tuberculosis in the future. The list of upregulated genes obtained in this
      study includes many genes found to be upregulated in other models of M.
      tuberculosis persistence. Thirteen upregulated genes, which are common for
      different models, can be considered as potential targets for the development of
      new anti-tuberculosis drugs directed mainly against latent tuberculosis.

PMID- 22649604
TI  - Covalent binding antibodies suppress advanced glycation: on the innate tier of
      adaptive immunity.
AB  - Non-enzymatic protein glycation is a source of metabolic stress that contributes
      to cytotoxicity and tissue damage. Hyperglycemia has been linked to elevation of
      advanced glycation endproducts, which mediate much of the vascular pathology
      leading to diabetic complications. Enhanced glycation of immunoglobulins and
      their accelerated vascular clearance is proposed as a natural mechanism to
      intercept alternative advanced glycation endproducts, thereby mitigating
      microvascular disease. We reported that antibodies against the glycoprotein KLH
      have elevated reactivity for glycopeptides from diabetic serum. These reactions
      are mediated by covalent binding between antibody light chains and carbonyl
      groups of glycated peptides. Diabetic animals that were immunized to induce
      reactive antibodies had attenuated diabetic nephropathy, which correlated with
      reduced levels of circulating and kidney-bound glycation products. Molecular
      analysis of antibody glycation revealed the preferential modification of light
      chains bearing germline-encoded lambda V regions. We previously noted that
      antibody fragments carrying V regions in the germline configuration are selected
      from a human Fv library by covalent binding to a reactive organophosphorus ester.
      These Fv fragments were specifically modified at light chain V region residues,
      which map to the combining site at the interface between light and heavy chains.
      These findings suggest that covalent binding is an innate property of antibodies,
      which may be encoded in the genome for specific physiological purposes. This
      hypothesis is discussed in context with current knowledge of the natural
      antibodies that recognize altered self molecules and the catalytic autoantibodies
      found in autoimmune disease.

PMID- 22649602
TI  - New approaches for cancer treatment: antitumor drugs based on gene-targeted
      nucleic acids.
AB  - Currently, the main way to fight cancer is still chemotherapy. This method of
      treatment is at the height of its capacity, so, setting aside the need for
      further improvements in traditional treatments for neoplasia, it is vital to
      develop now approaches toward treating malignant tumors. This paper reviews
      innovational experimental approaches to treating malignant malformations based on
      the use of gene-targeted drugs, such as antisense oligonucleotides (asON), small
      interfering RNA (siRNA), ribozymes, and DNAzymes, which can all inhibit oncogene
      expression. The target genes for these drugs are thoroughly characterized, and
      the main results from pre-clinical and first-step clinical trials of these drugs
      are presented. It is shown that the gene-targeted oligonucleotides show
      considerable variations in their effect on tumor tissue, depending on the target
      gene in question. The effects range from slowing and stopping the proliferation
      of tumor cells to suppressing their invasive capabilities. Despite their
      similarity, not all the antisense drugs targeting the same region of the mRNA of
      the target-gene were equally effective. The result is determined by the
      combination of the drug type used and the region of the target-gene mRNA that it
      complements.

PMID- 22649608
TI  - A Comparison of Target Gene Silencing using Synthetically Modified siRNA and
      shRNA That Express Recombinant Lentiviral Vectors.
AB  - RNA-interference is an effective natural mechanism of post-transcriptional
      modulation of gene expression. RNA-interference mechanism exist as in high
      eukaryotes both animals and plants as well in lower eukaryotes and viruses. RNA
      interference is now used as a powerful tool in study of functional gene activity
      and many essential for fundamental biology results was obtained with this
      approach. Also it's widely believed that RNA-interference could be used in
      working out of new therapeutic medicine against malignant, infectious and
      hereditary diseases. One of the main problems of these developments is search of
      effective methods of siRNA transfer into the target cells. At present time for
      these purpose different sorts of transfect ions or viral transduction are used.
      At present article the results of comparison of inhibition of expression of
      oncogene AML-ET O by synthetic siRNA and by recombinant lentiviruses coding for
      corresponding shRNA are presented.

PMID- 22649607
TI  - Telomerase Complex from Yeast Saccharomyces cerevisiae Contains a Biotinylated
      Component.
AB  - Telomerase adds telomeric repeats to single-stranded DNA at the ends of the
      chromosomes. This enzyme is a ribonucleoprotein complex. Telomerase from yeast
      Saccharomyces cerevisiae consists of TLC1 RNA, which serves as a template for the
      synthesis of telomeric repeats, telomerase reverse transcriptase Est2p, and a
      number of accessory proteins (Est1p, Est3p, Ku70/Ku80, and Sm-complex). We found
      that the yeast telomerase complex contains a biotinylated component. The
      telomerase fraction containing biotinylated protein is active in vitro and
      constitutes a small part of the total amount of active telomerase isolated from
      cells. We speculate about the nature of the biotinylated component.

PMID- 22649609
TI  - Generation and characterization of human induced pluripotent stem cells.
AB  - Cell biology is one of the most rapidly developing branches in modern biology.
      The most interesting stages in early embryonic development for cell biology are
      those when a large number of cells are pluripotent. Inner-cell mass of blastocyst
      can be cultivated in vitro, and these cells are called embryonic stem cells. They
      are able to differentiate into different types of cells and tissues. But the
      greatest interest for practical application is the return (reprogramming) of
      adult cells into the pluripotent state. In our study for the first time induced
      pluripotent cells were derived from human umbilical vein endothelial cells by
      genetic reprogramming. We showed that these cells are similar to embryonic stem
      cells in their morphology, function, and molecular level. We are the first to
      show that reprogramming sufficiently changes X-chromosome chromatin state, which
      is normally inactive in female endothelial cells, towards its activation,
      providing evidence that endothelial cells are reprogrammed at an epigenetic
      level.

PMID- 22649610
TI  - Influence of pub Gene Expression on Differentiation of Mouse Embryonic Stem Cells
      into Derivatives of Ecto-, Meso-, and Endoderm in vitro.
AB  - The influence of low and high pub gene expression on the initial stages of the
      differentiation of mouse embryonic stem cells into derivatives of ecto-, meso-,
      and endoderm in vitro was investigated. As follows from the results of a RT -PCR
      analysis, the expression of the vimentin, somatostatin, GATA 4, and GATA 6 genes,
      being the markers of endodermal differentiation, does not vary in both the cells
      with high pub gene expression and the cells with low pub gene expression, as well
      as in the corresponding control lines. The cells with high pub gene expression
      are characterized by an increase in the expression of mesodermal differentiation
      gene-markers (trI card, trI skel, c-kit, and IL-7), whereas the cells with low
      pub gene expression are specified by a decrease in their expression. According to
      the analyses carried out, the reverse is characteristic of the expression of
      ectodermal differentiation gene-markers (nestin, <=-III tubulin, gfap, and th).
      Expression of these genes decreases in cell lines with high pub gene expression,
      whereas their expression increases with the decrease in pub gene expression.
      Hence, it is suggested that the variations in the pub gene expression in the
      embryonic stem cells influence significantly the mesodermal and ectodermal
      differentiation of these cells.

PMID- 22649611
TI  - Cell phenotypes in human amniotic fluid.
AB  - Stem cells capable of long-term proliferation and differentiation into different
      cell types may be a promising source of cells for regenerative medicine.
      Recently, much attention has been paid to fetal stem cells, among which are cells
      from amniotic fluid (AF). We have isolated amniotic stem cells from 3 AF samples.
      Flow cytometry, RT -PCR and immunohistochemistry have shown that these cells
      express mesenchymal (CD90, CD73, CD105, CD13, CD29, CD44, and CD146), neural (<=3
      tubulin, Nestin, and Pax6), epithelial (keratin 19 and p63) markers and also
      markers of pluripotency (Oct4, Nanog, and Rex-1). Transplantation of the cells to
      nude mice does not lead to tumor formation. Thus, putative stem/progenitor cells
      from AF are capable of long-term proliferation in vitro and the profile of gene
      expression led us to speculate that they have greater differentiation potential
      than mesenchymal stem cells and may be useful for cell therapy.

PMID- 22649612
TI  - Phage display on the base of filamentous bacteriophages: application for
      recombinant antibodies selection.
AB  - The display of peptides and proteins on the surface of filamentous bacteriophage
      is a powerful methodology for selection of peptides and protein domains,
      including antibodies. An advantage of this methodology is the direct physical
      link between the phenotype and the genotype, as an analyzed polypeptide and its
      encoding DNA fragment exist in one phage particle. Development of phage display
      antibody libraries provides repertoires of phage particles exposing antibody
      fragments of great diversity. The biopanning procedure facilitates selection of
      antibodies with high affinity and specificity for almost any target. This review
      is an introduction to phage display methodology. It presents recombinant
      antibodies display in more details:, construction of phage libraries of antibody
      fragments and different strategies for the biopanning procedure.

PMID- 22649614
TI  - Genetic view on the phenomenon of combined diseases in man.
AB  - In clinical medicine, the phenomenon of polypathy, as a particular object of
      investigation, was first put forth by French clinicians at the end of the 19th
      century through the "arthritismus" doctrine. In the first half of the 20th
      century, German paediatricians singled out "syntropias," which are combinations
      of diseases with common pathophysiological mechanisms, and "dystropias," which
      are diseases that rarely co-occur in one individual. In the present paper,
      syntropy/dystropy is defined as a natural generic nonrandom phenomenon with an
      evolutionary-genetic basis. The genes involved in the development of syntropy are
      called "syntropic genes," whereas the genes that co-participate in
      pathophysiological mechanisms and prevent the co-occurrence of particular
      phenotypes are called "dystropic genes." Prospects for studying the genetic basis
      of this phenomenon are highlighted. The publicly available database HuGENet can
      be used in order to identify syntropic genes, as will be shown as examples in an
      analysis of cardiovascular diseases.

PMID- 22649615
TI  - Achievements and peculiarities in studies of ancient DNA and DNA from complicated
      forensic specimens.
AB  - Studies of ancient DNA specimens started 25 years ago. At that time short
      mitochondrial DNA (mtDNA) fragments were the main targets in ancient DNA studies.
      The last three years were especially productive in the development of new methods
      of DNA purification and analysis. Complete mtDNA molecules and relatively large
      fragments of nuclear DNA are the targets of ancient DNA studies today. Ancient
      DNA studies allowed us to study organisms that went extinct more than ten
      thousand years ago, to reconstruct their phenotypic traits and evolution. Ancient
      DNA analyses can help understand the development of ancient human populations and
      how they migrated. A new evolutionary hypothesis and reconstruction of the biota
      history have been re-created from recent ancient DNA data. Some peculiarities and
      problems specific to the study of ancient DNA were revealed, such as very limited
      amounts of DNA available for study, the short length of the DNA fragments, breaks
      and chemical modifications in DNA molecules that result in "postmortem" mutations
      or complete blockage of DNA replication in vitro. The same specific features of
      DNA analysis were revealed for specimens from complicated forensic cases that
      result in the lack of experimental data or interpretation problems.. Here, we
      list the specific features of ancient DNA methodology and describe some
      achievements in fundamental and applied research of ancient DNA, including our
      own work in the field.

PMID- 22649616
TI  - Genome paths: a way to personalized and predictive medicine.
AB  - The review is devoted to the impact of human genome research on progress in
      modern medicine. Basic achievements in genome research have resulted in the
      deciphering of the human genome and creation of a molecular landmarks map of the
      human haploid genome (HapMap Project), which has made a tremendous contribution
      to our understanding of common genetic and multifactorial (complex) disorders.
      Current genome studies mainly focus on genetic testing and gene association
      studies of multifactorial (complex) diseases, with the purpose of their efficient
      diagnostics and prevention . Identification of candidate ("predisposition") genes
      participating in the functional genetic modules underlying each common disorder
      and the use of this genetic background to elaborate sophisticated measures to
      efficiently prevent them constitutes a major goal in personalized molecular
      medicine. The concept of a genetic pass as an individual DNA databank reflecting
      inherited human predisposition to different complex and monogenic disorders, with
      special emphasis on its present state, and the numerous difficulties related to
      the practical implementation of personalized medicine are outlined. The problems
      related to the uncertainness of the results of genetic testing could be overcome
      at least partly by means of new technological achievements in genome research
      methods, such as genome-wide association studies (GWAS), massive parallel DNA
      sequencing, and genetic and epigenetic profiling. The basic tasks of genomic
      today could be determined as the need to properly estimate the clinical value of
      genetic testing and its applicability in clinical practice. Feasible ways towards
      the gradual implementation of personal genetic data, in line with routine
      laboratory tests, for the benefit of clinical practice are discussed.

PMID- 22649617
TI  - D-Arabinose Methabolism: Characterization of Bifunctional
      Arabinokinase/Pyrophosphorylase of Leishmania major.
AB  - In this work we describe an unusual enzyme from Leishmania major
      (Arabinokinase/Pyrophosphorylase) that catalyzes the synthesis of GDP-D
      arabinopyranose (GDP-D-Arap) via a D-arabinose-1-phosphate intermediate in the
      presence of ATP and GTP. Our data indicate GDP-D-Arap transport in vivo by the
      LPG2 multispecific nucleotide sugar transporter into the Leishmania Golgi
      apparatus, in which it can be used by glycosyltransferases as a donor substrate
      for glycosylation.

PMID- 22649618
TI  - Protein tyrosine kinase panel as a tool for anticancer drug design.
AB  - The discovery of the pharmaceutical potential of small molecule inhibitors of
      oncogenic protein tyrosine kinases is one of the directions in target therapy in
      oncology. Presently, investigations aiming at developing new therapeutically
      important inhibitors have to be based on a combination of computational and
      experimental approaches including biochitalicical, cell-based or in silico
      screening and the study of the three-dimensional structure of the kinase active
      center, in complex with an inhibitor, using crystallography and X-ray analysis or
      molecular modeling. This work is an example of a combination of inhibitor
      experimental search with the computational analysis of the potential mechanism of
      the inhibitors' action, which allowed to propose the 2-hydroxyphenol group as a
      scaffold for the design of new tyrosine kinase inhibitors.

PMID- 22649613
TI  - Chemical and functional aspects of posttranslational modification of proteins.
AB  - This paper reviews the chemical and functional aspects of the posttranslational
      modifications of proteins, which are achieved by the addition of various groups
      to the side chain of the amino acid residue backbone of proteins. It describes
      the main prosthetic groups and the interaction of these groups and the apoenzyme
      in the process of catalysis, using pyridoxal catalysis as an example. Much
      attention is paid to the role of posttranslational modification of proteins in
      the regulation of biochemical processes in live organisms, and especially to the
      role of protein kinases and their respective phosphotases. Methylation and
      acetylation reactions and their role in the "histone code", which regulates
      genome expression on the transcription level, are also reviewed. This paper also
      describes the modification of proteins by large hydrophobic residues and their
      role in the function of membrane-associated proteins. Much attention is paid to
      the glycosylation of proteins, which leads to the formation of glycoproteins. We
      also describe the main non-enzymatic protein modifications such as glycation,
      homocysteination, and desamida-tion of amide residues in dibasic acids.

PMID- 22649619
TI  - Atomic Resolution Crystal Structure of NAD(+)-Dependent Formate Dehydrogenase
      from Bacterium Moraxella sp. C-1.
AB  - The crystal structure of the ternary complex of NAD+-dependent formate
      dehydrogenase from the methylotrophic bacterium Moraxella sp. C-1 with the
      cofactor (NAD+) and the inhibitor (azide ion) was established at 1.1 A
      resolution. The complex mimics the structure of the transition state of the
      enzymatic reaction. The structure was refined with anisotropic displacitalicents
      parameters for non-hydrogen atoms to a R factor of 13.4%. Most of the nitrogen,
      oxygen, and carbon atoms were distinguished based on the analysis of the
      titalicperature factors and electron density peaks, with the result that side
      chain rotamers of histidine residues and most of asparagine and glutamine
      residues were unambiguously determined. A comparative analysis of the structure
      of the ternary complex determined at the atomic resolution and the structure of
      this complex at 1.95 A resolution was performed. In the atomic resolution
      structure, the covalent bonds in the nicotinamide group are somewhat changed in
      agreitalicent with the results of quantum mechanical calculations, providing
      evidence that the cofactor acquires a bipolar form in the transition state of the
      enzymatic reaction.

PMID- 22649620
TI  - Mutation of Residue betaF71 of Escherichia coli Penicillin Acylase Results in
      Enhanced Enantioselectivity and Improved Catalytic Properties.
AB  - Residue phenylalanine 71 of the beta-chain of penicillin acylase from E. coli is
      involved in substrate binding and chiral discrimination of its enantiomers.
      Different amino acid residues have been introduced at position betaF71, and the
      mutants were studied with respect to their enantioselectivity and substrate
      specificity. Some mutants demonstrated remarkably improved catalytic activity.
      Moreover, mutation of betaF71 residue allowed to enhance penicillin acylase
      enantioselectivity. The catalytic activity to the specific substrates was
      improved up to 36 times, most notably for K, R, and L mutants. Increased activity
      to a D-phenylglycine derivative - a valuable specificity improvement for
      biocatalytic synthesis of new penicillins and cephalosporins - was shown for
      betaF71R and betaF71L mutants. The synthetic capacity of penicillin acylase with
      6-aminopenicillanic acid as an external nucleophile was especially sensitive to
      mutation of the beta71 residue in contrast to the synthesis with 7
      aminodeacetoxycephalosporanic acid.

PMID- 22649621
TI  - Genotoxic effects of silver nanoparticles on mice in vivo.
AB  - The toxic and genotoxic effects of silver nanoparticles were studied on injected
      mice (BALB/c line) in vivo. A water solution of silver nanoparticles (SNP) with
      particle sizes of 9+/-6 nm was obtained by means of the original method of
      biochemical synthesis. The effect of the SNP solution was compared to those of
      AOT (anionic surfactant used as SNP stabilizer) and silver nitrate (i.e. Ag+
      ions) introduced as water solutions. In studies of the toxic effects, the death
      of mice was registered 12-24 hours after injection only at two maximum dozes of
      SNP (equivalent to 0.54 and 0.36 gAg/l). It is shown that the toxic effect
      decreases in the sequence SNP>AOT>>AgNO3. The LE50/30 values for SNP and AOT are
      equal to 0.30+/-0.07 gAg/l and 13.3+/-2.1 gAg/l, respectively. Genotoxic effects
      were assessed by the abnormal sperm heads test and neutral Comet assay. The
      frequencies of abnormal sperm heads (ASHs) did not differ after treatment by SNP
      and AOT, but both were significantly higher than those found with AgNO3 and in
      control mice. Comet assay showed an increase of the DNA percentage in the comet
      tail in spleen cells after the injection of SNP and AOT in concentrations of <=
      LE50/30. Tail DNA % was 32.8+/-1.3 and 26.3+/-1.7%, respectively, vs 16.2+/-0.7%
      for the untreated control. To sum up, these tests showed that the genotoxic
      effects of the SNP solution are associated with the presence of AOT rather than
      SNP.

PMID- 22649622
TI  - Combining two technologies for full genome sequencing of human.
AB  - At present, the new technologies of DNA sequencing are rapidly developing
      allowing quick and efficient characterisation of organisms at the level of the
      genome structure. In this study, the whole genome sequencing of a human (Russian
      man) was performed using two technologies currently present on the market -
      Sequencing by Oligonucleotide Ligation and Detection (SOLiDTM) (Applied
      Biosystems) and sequencing technologies of molecular clusters using fluorescently
      labeled precursors (Illumina). The total number of generated data resulted in
      108.3 billion base pairs (60.2 billion from Illumina technology and 48.1 billion
      from SOLiD technology). Statistics performed on reads generated by GAII and SOLiD
      showed that they covered 75% and 96% of the genome respectively. Short
      polymorphic regions were detected with comparable accuracy however, the absolute
      amount of them revealed by SOLiD was several times less than by GAII. Optimal
      algorithm for using the latest methods of sequencing was established for the
      analysis of individual human genomes. The study is the first Russian effort
      towards whole human genome sequencing.

PMID- 22649623
TI  - Cell Regulation of Proliferation and Differentiation ex vivo for Cells Containing
      Ph Chromosome in Chronic Myeloid Leukemia.
AB  - Cell regulation of Ph(+)cell proliferation and differentiation has been studied
      ex vivo in various chronic myeloid leukemia (CML) patients. The regulation is
      provided by alternation of effective stages of proliferation and maturation with
      inhibition of Ph(+) cell proliferation by accumulating neutrophils under
      apoptosis blockage. The alternation of stages consists of switching stage 1
      (effective proliferation) to stage 2 (effective maturation) and proceeds
      according to the 1/2 -1/2/1 or 2/1-2/1/2/1 schemes. The kinetic plots of
      alternations pass through control points of crossing plots, where the parameters
      of proliferation and maturation are equal. The indices of P/D efficiency (ratio
      of proliferation and maturation rates) are 1.06+/-0.23 and don't depend on time,
      alternation order, or sources of Ph(+) cells - CML patients. During stages
      alternation, conversely, the parameters of Ph+ cell proliferation and maturation
      vary. The proliferation stages are characterized by increased proliferating cells
      content, a decreased number of neutrophils, and apoptosis induction. At the
      maturation stages, conversely, apoptosis is inhibited, the number of mature
      neutrophils increases, while immature Ph(+) cells decrease. High content
      neutrophils inhibit the proliferation of Ph(+) cells and impair their own
      maturation by inversion of maturation order, probably through a feedback
      mechanism. The regulation differences ex vivo reveal three types of Ph(+) cells
      from various individual CML patients, distinguished by the number and duration of
      alternating stages of proliferation and maturation. Ph(+) cells types 1 and 2
      have one prolonged stage of effective proliferation or effective maturation with
      efficiency indices P/D(1) = 1-20 or P/D(2) <= 1. At the same time period, the
      proliferation and differentiation of the Ph(+) cells type 3 proceeds with
      repeated alternations of stages with P/D(1) = 1-4 or P/D(2) <= 1. Type 1 Ph(+)
      cells (~20%) were isolated from patients in advanced stages of CML, while Ph(+)
      cells types 2 and 3 (30 and 50% correspondingly) were isolated from CML chronic
      phase patients sensitive to chemotherapy.

PMID- 22649624
TI  - Deamination of 5-methylcytosine residues in Mammalian cells.
AB  - DNA demethylation in mammalia occurs after fertilization and during embryogenesis
      and accompanies cell aging and cancer transformation. With the help of the primer
      extension reaction, MALDI MS and DNA cleavage by thymine DNA glycosylase
      deamination of 5-methylcytosine residues has been shown to take place when the
      model methylated DNA duplexes are treated with nuclear extracts from the cell
      lines CHO, HeLa, and Skov3. The hypothesis that deamination of 5-methylcytosine
      is the first stage of demethylation in mammalia has been postulated.

PMID- 22649625
TI  - Study of Molecular Mechanisms Involved in the Pathogenesis of Immune-Mediated
      Inflammatory Diseases, using Psoriasis As a Model.
AB  - Psoriasis was used as a model to analyze the pathogenetic pathways of immune
      mediated inflammatory diseases, and the results of bioinformatic, molecular
      genetic and proteomic studies are provided. Cell mechanisms, common for the
      pathogenesis of psoriasis, as well as Crohn's disease, are identified. New
      approaches for immune-mediated diseases are discussed.

PMID- 22649626
TI  - Mechanisms of gravitational sensitivity of osteogenic precursor cells.
AB  - This report is a detailed review of the current data on the mechanic and
      gravitational sensitivity of osteoblasts and osteogenic precursor cells in vitro.
      It summarizes the numerous responses of cells with an osteoblastic phenotype and
      osteogenic precursor cells and especially their responses to the alteration of
      their mechanic or gravitational surroundings. The review also discusses the
      osteogenic cell's pathways of signal transduction and the mechanisms of
      gravitational sensitivity. It was shown that the earliest multipotent stromal
      precursor cells of an adult organism's bone marrow can sense changes of intensity
      in a gravitational or mechanic field in model conditions, which may play a
      certain role in the development of osteopenia in microgravity.

PMID- 22649627
TI  - Selectivity of Enzymatic Conversion of Oligonucleotide Probes during Nucleotide
      Polymorphism Analysis of DNA.
AB  - The analysis of DNA nucleotide polymorphisms is one of the main goals of DNA
      diagnostics. DNA-dependent enzymes (DNA polymerases and DNA ligases) are widely
      used to enhance the sensitivity and reliability of systems intended for the
      detection of point mutations in genetic material. In this article, we have
      summarized the data on the selectiveness of DNA-dependent enzymes and on the
      structural factors in enzymes and DNA which influence the effectiveness of
      mismatch discrimination during enzymatic conversion of oligonucleotide probes on
      a DNA template. The data presented characterize the sensitivity of a series of
      DNA-dependent enzymes that are widely used in the detection of noncomplementary
      base pairs in nucleic acid substrate complexes. We have analyzed the spatial
      properties of the enzyme-substrate complexes. These properties are vital for the
      enzymatic reaction and the recognition of perfect DNA-substrates. We also discuss
      relevant approaches to increasing the selectivity of enzyme-dependent reactions.
      These approaches involve the use of modified oligonucleotide probes which
      "disturb" the native structure of the DNA-substrate complexes.

PMID- 22649628
TI  - Regulation of Immunogen Processing: Signal Sequences and Their Application for
      the New Generation of DNA-Vaccines.
AB  - Immunization with naked genes (DNA-immunization) is a perspective modern approach
      to prophylactic as well as therapeutic vaccination against pathogens, as well as
      cancer and allergy. A panel of DNA immunogens has been developed, some are
      already in the clinical trials. However, the immunogenicity of DNA vaccines,
      specifically of those applied to humans, needs a considerable improvement. There
      are several approaches to increase DNA vaccine immunogenicity. One approach
      implies the modifications of the encoded immunogen that change its processing and
      presentation, and thus the overall pattern of anti-immunogen response. For this,
      eukaryotic expression vectors are constructed that encode the chimeric proteins
      composed of the immunogen and specialized targeting or signal sequences. The
      review describes a number of signals that if fused to immunogen, target it into
      the predefined subcellular compartments. The review gives examples of their
      application for DNA-immunization.

PMID- 22649629
TI  - Ecological basis for rational phage therapy.
AB  - Understanding the mutual interactions of bacterial and phage populations in the
      environment of a human or animal body is essential in any attempt to influence
      these complex processes, particularly for rational phage therapy. Current
      knowledge on the impact of naturally occurring bacteriophages on the populations
      of their host bacteria, and their role in the homeostasis maintenance of a macro
      host, is still sketchy. The existing data suggest that different mechanisms
      stabilize phage-bacteria coexistence in different animal species or different
      body sites. The defining set of parameters governing phage infection includes
      specific physical, chemical, and biological conditions, such as pH, nutrient
      densities, host prevalence, relation to mucosa and other surfaces, the presence
      of phage inhibiting substances, etc. Phage therapy is also an ecological process
      that always implies three components that form a complex pattern of interactions:
      populations of the pathogen, the bacteriophages used as antibacterial agents, and
      the macroorganism. We present a review of contemporary data on natural
      bacteriophages occuring in human- and animal-body associated microbial
      communities, and analyze ecological and physiological considerations that
      determine the success of phage therapy in mammals.

PMID- 22649630
TI  - Calcium signaling and neurodegeneration.
AB  - Neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's
      disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and
      spinocerebellar ataxias (SCA) are very important both for fundamental science and
      for practical medicine. Despite extensive research into the causes of these
      diseases, clinical researchers have had very limited progress and, as of now,
      there is still no cure for any of these diseases. One of the main obstacles in
      the way of creating treatments for these disorders is the fact that their
      etiology and pathophysiology still remain unclear. This paper reviews results
      that support the so-called "calcium hypothesis of neurodegenerative diseases."
      The calcium hypothesis states that the atrophic and degenerative processes in the
      neurons of AD, PD, ALS, HD, and SCA patients are accompanied by alterations in
      calcium homeostasis. Moreover, the calcium hypothesis states that this
      deregulation of calcium signaling is one of the early-stage and key processes in
      the pathogenesis of these diseases. Based on the results we reviewed, we conclude
      that the calcium channels and other proteins involved in the neuronal calcium
      signaling system are potential drug targets for AD, PD, ALS, HD, and SCA therapy.

PMID- 22649631
TI  - A Novel High-Resolving Method for Genomic PCR-Fingerprinting of Enterobacteria.
AB  - We developed a novel PCR-fingerprinting system for differentiation of
      enterobacterial strains using a single oligonucleotide primer IS1tr that matches
      the inverted terminal repeats of the IS1 insertion element. Compared to widely
      used BOX-PCR and ribotyping methods, our system features higher resolution
      allowing differentiation of closely related isolates that appear identical in BOX
      PCR and ribotyping but differ in their phage sensitivity. The IS1-profiling
      system is less sensitive to the quality of the material and equipment used. At
      the same time, BOX-PCR is more universal and suitable for bacterial strain
      grouping and reconstruction of the low-distance phylogeny. Thus, our system
      represents an important supplement to the existing set of tools for bacterial
      strain differentiation; it is particularly valuable for a detailed investigation
      of highly divergent and rapidly evolving natural bacterial populations and for
      studies on coliphage ecology. However, some isolates could not be reliably
      differentiated by IS1-PCR, because of the low number of bands in their patterns.
      For improvement of IS1-fingerprinting characteristics, we offer to modify the
      system by introducing the second primer TR8834 hybridizing to the sequence of a
      transposase gene that is widely spread in enterobacterial genomes.

PMID- 22649632
TI  - Tumoricidal Activity of RNase A and DNase I.
AB  - In our work the antitumor and antimetastatic activities of RNase A and DNase I
      were studied using two murine models of pulmonary (Lewis lung carcinoma) and
      liver (hepatoma A-1) metastases. We found that intramuscular administration of
      RNase A at the dose range of 0.1-50 u g/kg retarded the primary tumor growth by
      20-40%, and this effect disappeared with the increase in RNase A dose over 0.5
      mg/kg. DNase I showed no effect on the primary tumor growth. The intramuscular
      administration of RNase A (0.35-7 u g/kg) or DNase I (0.02-2.3 mg/kg) resulted in
      a considerable decrease in the metastasis number into the lungs of animals with
      Lewis lung carcinoma and a decrease of the hepatic index of animals with hepatoma
      1A. A histological analysis of the organs occupied by metastases revealed that
      the administration of RNase A and DNase I induced metastasis pathomorphism as
      manifested by the destruction of oncocytes, an increase in necrosis and apoptosis
      foci in metastases, and mononuclear infiltration. Our data indicated that RNase A
      and DNase I are highly promising as supplementary therapeutics for the treatment
      of metastasizing tumors.

PMID- 22649633
TI  - Penicillin Acylase-Catalyzed Effective and Stereoselective Acylation of 1
      phenylethylamine in Aqueous Medium using Non-Activated Acyl Donor.
AB  - Until recently, the biocatalytic preparation of enantiomerically pure amines was
      based on stereoselective acyl transfer in an organic medium using activated acyl
      donors. The possibility of performing an effective and enantioselective enzymatic
      acylation of amines in an aqueous medium without using activated acyl donors was
      demonstrated for the first time as the example of direct condensation of
      phenylacetic acid and racemic 1-phenylethylamine. Direct condensation of the acid
      and the amine took place at mild reaction conditions with a high initial rate
      (3.3 umole/(l.h)), degree of conversion (80% acylation of active amine
      enantiomer), and enantioselectivity (enantiomeric excess of the product was more
      than 95%). The suggested approach has remarkable advantages compared to enzymatic
      reactions in organic media and is of practical value for the biocatalytic
      preparation of enantiomerically pure compounds at mild conditions using readily
      available reagents.

PMID- 22649634
TI  - Assessment of Formate Dehydrogenase Stress Stability In vivo using Inactivation
      by Hydrogen Peroxide.
AB  - Kinetic studies on hydrogen peroxide-induced inactivation of mutant formate
      dehydrogenase from Pseudomonas sp. 101 (PseFDH Cys255Ala) suggest a simple
      bimolecular mechanism for enzyme reaction with the inactivation agent. In the
      excess of hydrogen peroxide, the decrease in enzyme activity follows first-order
      kinetics. Therefore, the first-order effective inactivation kinetic constants
      determined for various FDH forms at a constant H(2)O(2) concentration can be used
      as a quantitative measure of the enzyme stability. It was shown that two cysteine
      residues located in the active site formate- and coenzyme-binding domains (Cys145
      and Cys255, respectively) make similar contributions to the enzyme stability,
      while the contribution of Cys354 is insignificant. The inactivation kinetics of
      wild-type PseFDH, mutant PseFDH Cys145Ser/Cys255Ala, and FDH produced under
      stress conditions by bacterium  Staphylococcus aureus, higher plants Arabidopsis
      thaliana, and soya Glycine max, was studied. It was found that the stress-induced
      FDHs are at least 20 times more stable than the nonstress-induced PseFDH from 
      Pseudomonas  sp. 101 grown on methanol.

PMID- 22649635
TI  - Changes in the Proteasome Pool during Malignant Transformation of Mouse Liver
      Cells.
AB  - Multiple forms of proteasomes regulate cellular processes by destroying proteins
      or forming the peptides involved in those processes. Various pathologies,
      including carcinogenesis, are related to changes in the functioning of the
      proteasome forms. In this study, we looked at the changes in the pool of liver
      proteasomes during nodular regenerative hyperplasia and formation of adenoma and
      hepatocellular carcinoma in mice treated with Dipin, followed by partial liver
      resection. The relative content of various proteasome forms was determined using
      Western blot analysis. The chymotrypsin-like activity of proteasomes was assessed
      from the hydrolysis of the commercial Suc-LLVY-AMC substrate. It was found that
      changes in the proteasome pool appeared already during the formation of diffuse
      nodules, the changes being the increased expression of the X(beta5) constitutive
      subunit and the LMP7(beta5i) and LMP2(beta1i) immune subunits, accompanied by the
      increase of the total proteasome pool and the decrease in the chymotrypsin-like
      activity. These changes were more pronounced in hepatocellular carcinoma. The
      content of the total proteasome pool and the LMP2(beta1i) immune subunit and the
      chymotrypsin-like activity in adenoma were intermediate compared to those in the
      samples of liver with diffuse nodules and carcinoma. In addition, the level of
      the Rpt6 subunit present in the 19S proteasome activator was increased in
      carcinoma. Our results indicate that nodular regenerative hyperplasia and
      adenomatosis may be stages preceding carcinogenesis. We also conclude that there
      is a need to find signalling pathways that change the expression of various
      proteasome subunits during carcinogenesis. The 19S proteasome activator, which is
      overexpressed in malignant tumours, can be a promising target for the development
      of new anticancer drugs.

PMID- 22649636
TI  - New 5-modified pyrimidine nucleoside inhibitors of mycobacterial growth.
AB  - The WHO has declared tuberculosis (TB) a global health emergency. Therefore,
      there is an urgent need to discover and develop new anti-TB drugs. Here we report
      on a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of
      Myco-bacterium tuberculosis growth in vitro. A series of 2'-deoxy-, 3'-azido
      2',3'-dideoxy-, and 3'-amino-2',3'-dideoxypyrimidine nucleoside analogues bearing
      lengthy flexible alkyloxymethyl substituents exhibited marked inhibitory activity
      against M. tuberculosis in vitro. 5-Dodecyloxymethyl-2'-deoxyuridine was found to
      be a potent inhibitor of M. tuberculosis propagation in vitro. In contrast,
      monophosphates of the tested nucleosides were devoid of antimycobacterial
      activity. This new class of inhibitors seems to be a promising chemotherapeutic
      agent against TB and merits further studies.

PMID- 22649637
TI  - Induction of a Protective Heterosubtypic Immune Response Against the Influenza
      Virus by using Recombinant Adenoviral Vectors Expressing Hemagglutinin of the
      Influenza H5 Virus.
AB  - Influenza viruses are characterized by a high degree of antigenic variability,
      which causes the annual emergence of flu epidemics and irregularly timed
      pandemics caused by viruses with new antigenic and biological traits. Novel
      approaches to vaccination can help circumvent this problem. One of these new
      methods incorporates genetic vaccines based on adenoviral vectors. Recombinant
      adenoviral vectors which contain hemagglutinin-encoding genes from avian H5N1 and
      H5N2 (Ad-HA5-1 and Ad-HA5-2) influenza viruses were obtained using the AdEasy
      Adenoviral Vector System (Stratagene). Laboratory mice received a double
      intranasal vaccination with Ad-HA5-1 and Ad-HA5-2. This study demonstrates that
      immunization with recombinant adenoviruses bearing the N 5 influenza virus
      hemagglutinin gene induces a immune response which protects immunized mice from a
      lethal dose of the H5 influenza virus. Moreover, it also protects the host from a
      lethal dose of the H1 virus, which belongs to the same clade as H5, but does not
      confer protection from the subtype H3 influenza virus, which belongs to a
      different clade.

PMID- 22649638
TI  - Induced Pluripotent Stem Cells: Problems and Advantages when Applying them in
      Regenerative Medicine.
AB  - Induced pluripotent stem cells (iPSCs) are a new type of pluripotent cells that
      can be obtained by reprogramming animal and human differentiated cells. In this
      review, issues related to the nature of iPSCs are discussed and different methods
      of iPSC production are described. We particularly focused on methods of iPSC
      production without the genetic modification of the cell genome and with means for
      increasing the iPSC production efficiency. The possibility and issues related to
      the safety of iPSC use in cell replacement therapy of human diseases and a study
      of new medicines are considered.

PMID- 22649639
TI  - Bioglycans and natural glycosides as a promising research topic in bioorganic
      chemistriy.
AB  - This review defines bioorganic chemistry as one of the most important
      constituents of physico-chemical biology, which is a fundamental life science.
      The problems and goals of bioorganic chemistry are examined through a
      comparatively small number of examples. Bioorganic chemistry is supposed to be a
      logical continuation of the chemistry of the natural substances that arose many
      years ago. Bioorganic chemistry has contributed some achievements in solving the
      problems of the chemical structure, biological function, and physiological
      activity of biopolymers and low-molecular-weight bioregulators, as well as in the
      elucidation of the molecular mechanisms of different life processes. The most
      striking achievements in bioorganic chemistry are discussed in this paper.
      However, this review discusses not only the general achievements in this field of
      science, but also research data obtained by scientists from the Pacific Institute
      of Bioorganic Chemistry, Far East Branch, Russian Academy of Sciences
      (Vladivostok, Russia), and the Institute of Physiology, Komi Science Centre, The
      Urals Branch, Russian Academy of Sciences (Syktyvkar, Russia). Particular
      attention is focused on comprehensive research into polysaccharides and
      biopolymers (bioglycans) and some natural glycosides that the author of this
      review has studied for a long time. The author has worked in these institutes for
      a long time and was honored by being chosen to head one of the scientific schools
      in the field of bioorganic chemistry and molecular immunology.

PMID- 22649640
TI  - New trends in nucleoside biotechnology.
AB  - This review focuses on new trends in nucleoside biotechnology, which have emerged
      during the last decade. Continuously growing interest in the study of this class
      of compounds is fueled by a number of factors: (  i  ) a growing need for large
      scale production of natural 2 ' -deoxy- beta -D-ribonucleosides as well as their
      analogs with modifications in the carbohydrate and base fragments, which can then
      be used for the synthesis and study of oligonucleotides, including short
      interfering RNA (siRNA), microRNA (miRNA), etc.; (  ii  ) a necessity for the
      development of efficient practical technologies for the production of
      biologically important analogs of natural nucleosides, including a number of
      anticancer and antiviral drugs; (  iii  ) a need for further study of known and
      novel enzymatic transformations and their use as tools for the efficient
      synthesis of new nucloside analogs and derivates with biomedical potential. This
      article will review all of these aspects and also include a brief retrospect of
      this field of research.

PMID- 22649642
TI  - Bioinformatic Analysis, Molecular Modeling of Role of Lys65 Residue in Catalytic
      Triad of D-aminopeptidase from Ochrobactrum anthropi.
AB  - A bioinformatic and phylogenetic study has been performed on a family of
      penicillin-binding proteins including D-aminopeptidases, D-amino acid amidases,
      DD-carboxypeptidases, and beta -lactamases. Significant homology between D
      aminopeptidase from Ochrobactrum anthropi and other members of the family has
      been shown and a number of conserved residues identified as S62, K65, Y153, N155,
      H287, and G289. Three of those (Ser62, Lys65, and Tyr153) form a catalytic
      triangle - the proton relay system that activates the generalized nucleophile in
      the course of catalysis. Molecular modeling has indicated the conserved residue
      Lys65 to have an unusually low pKa value, which has been confirmed experimentally
      by a study of the pH-profile of D-aminopeptidase catalytic activity. The
      resulting data have been used to elucidate the role of Lys65 in the catalytic
      mechanism of D-aminopeptidase as a general base for proton transfer from
      catalytic Ser62 to Tyr153, and vice versa, during the formation and hydrolysis of
      the acyl - enzyme intermediate.

PMID- 22649641
TI  - Skeletal muscle activity and the fate of myonuclei.
AB  - Adult skeletal muscle fiber is a symplast multinuclear structure developed in
      ontogenesis by the fusion of the myoblasts (muscle progenitor cells). The nuclei
      of a muscle fiber (myonuclei) are those located at the periphery of fiber in the
      space between myofibrils and sarcolemma. In theory, a mass change in skeletal
      muscle during exercise or unloading may be associated with the altered myonuclear
      number, ratio of the transcription, and translation and proteolysis rates. Here
      we review the literature data related to the phenomenology and hypothetical
      mechanisms of the myonuclear number alterations during enhanced or reduced muscle
      contractile activity. In many cases (during severe muscle and systemic diseases
      and gravitational unloading), muscle atrophy is accompanied by a reduction in the
      amount of myonuclei. Such reduction is usually explained by the development of
      myonuclear apoptosis. A myonuclear number increase may be provided only by the
      satellite cell nuclei incorporation via cell fusion with the adjacent myofiber.
      It is believed that it is these cells which supply fiber with additional nuclei,
      providing postnatal growth, work hypertrophy, and repair processes. Here we
      discuss the possible mechanisms controlling satellite cell proliferation during
      exercise, functional unloading, and passive stretch.

PMID- 22649643
TI  - Development of Recombinant Vaccine against A(H1N1) 2009 Influenza Based on Virus
      like Nanoparticles Carrying the Extracellular Domain of M2 Protein.
AB  - The conventional vaccines currently being used to deal with influenza are based
      on a virus obtained in chicken embryos or its components. The high variability of
      the major immunogenic surface proteins - hemagglutinin and neuraminidase-require
      the development of strain-specific vaccines that match the antigenic specificity
      of a newly emerging virus. Recombinant vaccines based on single viral proteins
      that could be easily produced in standard expression systems are attractive
      alternatives to traditional influenza vaccines. We constructed recombinant
      nanosized virus-like particles based on a nuclear antigen of the hepatitis B
      virus. These particles expose on the surface the extracellular domain of the M2
      protein of the highly pathogenic A(H1N1) 2009 influenza virus. The methods of
      production of these virus-like particles in  Escherichia coli  and their
      purification were developed. Experiments on animals show that M2sHBc particles
      are highly immunogenic in mice and provide complete protection against the lethal
      influenza challenge.

PMID- 22649644
TI  - Effects of Myosin "essential" light chain A1 on the aggregation properties of the
      Myosin head.
AB  - We compared the thermal aggregation properties of two isoforms of the isolated
      myosin head (myosin subfragment 1, S1) containing different "essential" (or
      "alkali") light chains, A1 or A2. Temperature dependencies for the aggregation of
      these two S1 isoforms, as measured by the increase in turbidity, were compared
      with the temperature dependencies of their thermal denaturation obtained from
      differential scanning calorimetry (DSC) experiments. At relatively high ionic
      strength (in the presence of 100 mM KCl) close to its physiological values in
      muscle fibers, we have found no appreciable difference between the two S1
      isoforms in their thermally induced aggregation. Under these conditions, the
      aggregation of both S1 isoforms was independent of the protein concentration and
      resulted from their irreversible denaturation, which led to the cohesion of
      denatured S1 molecules. In contrast, a significant difference between these S1
      isoforms was revealed in their aggregation measured at low ionic strength. Under
      these conditions, the aggregation of S1 containing a light chain A1 (but not A2)
      was strongly dependent on protein concentration, the increase of which (from
      0.125 to 2.0 mg/ml) shifted the aggregation curve by ~10 degrees towards the
      lower temperatures. It has been concluded that the aggregation properties of this
      S1 isoform at low ionic strength is basically determined by intermolecular
      interactions of the N-terminal extension of the A1 light chain (which is absent
      in the A2 light chain) with other S1 molecules. These interactions seem to be
      independent of the S1 thermal denaturation, and they may take place even at low
      temperature.

PMID- 22649645
TI  - Influence of Ion Strength and pH on Thermal Stability of Yeast Formate
      Dehydrogenase.
AB  - The kinetics of the thermal inactivation of recombinant wild-type formate
      dehydrogenase from  Candida boidinii  yeast was studied in the temperature range
      of 53-61(o)C and pH 6.0, 7.0, and 8.0. It was shown that the loss of the enzyme's
      activity proceeds via a monomolecular mechanism. Activation parameters ?N(-) and
      ?S(-) were calculated based on the temperature relations dependence of
      inactivation rate constants according to the transition state theory. Both
      parameters are in a range that corresponds to globular protein denaturation
      processes. Optimal conditions for the stability of the enzyme were high
      concentrations of the phosphate buffer or of the enzyme substrate sodium formate
      at pH = 7.0.

PMID- 22649646
TI  - Anionic lipids: determinants of binding cytotoxins from snake venom on the
      surface of cell membranes.
AB  - The cytotoxic properties of cytotoxins (CTs) from snake venom are mediated by
      their interaction with the cell membrane. The hydrophobic pattern containing the
      tips of loops I-III and flanked by polar residues is known to be a membrane
      binding motif of CTs. However, this is not enough to explain the difference in
      activity among various CTs which are similar in sequence and in 3D structure. The
      mechanism of further CT-membrane interaction leading to pore formation and cell
      death still remains unknown. Published experimental data on the specific
      interaction between CT and low molecular weight anionic components (sulphatide)
      of the bilayer point to the existence of corresponding ligand binding sites on
      the surface of toxin molecules. In this work we study the membrane-lytic
      properties of CT I, CT II (Naja oxiana), and Ct 4 (Naja kaouthia), which belong
      to different structural and functional types (P- and S-type) of CTs, by measuring
      the intensity of a fluorescent dye, calcein released from liposomes containing a
      phosphatidylserine (PS) lipid as an anionic component. Using molecular docking
      simulations, we find and characterize three sites in CT molecules that can
      potentially bind the PS polar head. Based on the data obtained, we suggest a
      hypothesis that CTs can specifically interact with one or more of the anionic
      lipids (in particular, with PS) contained in the membrane, thus facilitating the
      interaction between CTs and the lipid bilayer of a cell membrane.

PMID- 22649647
TI  - 2D-gel Electrophoresis As a Tool to Investigate the Composition of CD95 DISC.
AB  - Stimulation of CD95 (APO-1/Fas) leads to apoptosis induction in multicellular
      organisms. CD95-mediated apoptosis starts with the formation of the protein
      complex at the receptor CD95 (APO-1/Fas), which was named DISC (death-inducing
      signaling complex). In this work, the composition of the CD95 DISC in two
      different cell types was analyzed using proteomics approaches. Using 2D gels, the
      composition of the CD95 DISC was analyzed in the so-called Type I and Type II
      cells, which are characterized by different kinetics of apoptosis. The detailed
      analysis of the CD95 DISC performed by 2D gels demonstrated that, besides the
      well-established components of the CD95 DISC, which are present in both cell
      types (CD95, FADD and procaspase-8), there are a number of differential spots
      detected at the CD95 DISC of Type I  versus  Type II cells. Taken together, this
      work demonstrates the differential composition of the CD95 DISC of Type I  versus
      Type II cells.

PMID- 22649648
TI  - Derivation of induced pluripotent stem cells from fetal human skin fibroblasts.
AB  - The isolation and study of autologous human stem cells remain among the most
      urgent problems in cell biology and biomedicine to date. Induced pluripotent stem
      cells can be derived from human somatic cells by the overexpression of a number
      of genes. In this study we reprogrammed fetal human skin fibroblasts by
      transduction with retroviral vectors carrying murine  Oct4  ,  Sox2  ,  Klf4  ,
      and  c-Myc  cDNAs. As a result, cells with the protein expression and gene
      transcription pattern characteristic of human embryonic stem cells were derived.
      These induced pluripotent cells are capable of differentiation  in vitro  into
      the ectoderm, mesoderm, and endoderm derivatives.

PMID- 22649649
TI  - Toll-Like Receptors (TLRs): The Role in Tumor Progression.
AB  - Toll-like receptors (TLRs) are major components of the innate immune system that
      recognize the conserved molecular structures of pathogens (pathogen-associated
      molecular patterns; PAMPs). TLRs are found in many different cell types, ranging
      from epithelial to immunocompetent cells. TLR binding triggers the expression of
      several adapter proteins and downstream kinases, leading to the induction of key
      pro-inflammatory mediators. This results in the activation of both the innate
      immune response (elevated expression of antiapoptotic proteins, proinflammatory
      cytokines, and antibacterial proteins), as well as the adaptive immune response
      (maturation of the dendritic cells, antigen presentation, etc.). In consequence
      of their ability to enhance the specific and nonspecific immune reactions of an
      organism, TLR agonists are widely used in the therapy of infectious diseases and,
      as adjuvants, in the therapy of malignant neoplasia. However, to date, TLRs have
      had the opposite effects on tumor progression. On the one hand, TLR ligands can
      suppress tumor growth. On the other hand, TLR agonists can promote the survival
      of malignant cells and increase their resistance to chemotherapy. The purpose of
      this review is to summarize the available data on the effects of TLRs and their
      agonists on tumor progression, as well as the mechanisms underlying the
      differences in the effects of TLRs on tumor growth.

PMID- 22649650
TI  - Molecular basis of Mammalian embryonic stem cell pluripotency and self-renewal.
AB  - Mammalian embryonic stem cells (ESC) have a number of specific properties that
      make them a unique object of fundamental and applied studies. In culture, ESC can
      remain in an infinitely undifferentiated state and differentiate into descendants
      of all three germ layers - ectoderm, endoderm, and mesoderm - that is, they can
      potentially produce more than 200 cell types comprising the body of an adult
      mammal. These properties of ESC are refered to as self-renewal and pluripotency.
      In this review, the basic signal pathways implicated in the maintenance of ESC
      pluripotency are considered. The major genes comprising a subsystem of "internal
      regulators of pluripotency," their protein products and regulators, are
      characterized, and interaction with other factors is described as well. The role
      of epigenetic mechanisms and microRNAs in the system of ESC self-renewal and
      pluripotency, as well as the relationship between pluripotency and X-chromosome
      inactivation in female mammals, is discussed.

PMID- 22649653
TI  - Association of ERAP1 Allelic Variants with Risk of Ankylosing Spondylitis.
AB  - Ankylosing spondylitis (AS) belongs to a group of autoimmune diseases affecting
      the axial skeleton. Beside thehla-b*27allele, several other human genes that
      control the variety processes of immune homeostasis are considered to be
      associated with AS manifestation in different human populations. Among strong
      associated non-MHC geneserap1 encodingthe endoplasmic reticulum aminopeptidase 1
      isoform was recently identified by single nucleotide polymorphisms (SNPs) meta
      analysis. In our study we inspected the genetic association of five non
      synonymous coding SNPs fromerap1 withAS in Caucasians. We implemented the SSP-PCR
      system for precise genotyping of 87hla-b*27positive AS patients and 77hla
      b*27healthy donors from the Russian population. Considerable differences in
      allele's frequencies within patients vs control cohort were shown for 3 of 5 SNPs
      under investigation. Using the EM-algorhitm we reconstructed 3-marker haplotypes
      that distinguish with high probability two cohorts due to differences in the
      haplotypes frequencies. In such a way both the sensitive, CCT, haplotype and the
      protective, TTC, one were predicted. To verify the calculation we determined
      genuine frequencies of 5-marker haplotypes in AS cohort by haplotyping of
      individual cDNA samples using improved SSP-PCR primer set. We demonstrated that
      the frequencies ofin silicareconstucted haplotypes and the frequencies of
      experimentally detected haplotypes are in a good agreement. Frequency of the risk
      haplotype CCT (rs17482078/10050860/2287987) detected within AS cohort reaches
      88%, as well as the frequency calculated by EM-algorhitm.

PMID- 22649652
TI  - PEDF - A Noninhibitory Serpin with Neurotrophic Activity.
AB  - The pigment epithelium-derived factor (PEDF) is a glycoprotein with a molecular
      weight of 50 kDa belonging to the noninhibitory serpin family. It regulates
      several physiological processes, such as stimulation of retinoblastoma cell
      differentiation into neuron cells, and facilitation of the growth and viability
      of photoreceptor cells and neurons of the central nervous system. Moreover, this
      factor protects neuronal cells against apoptosis. PEDF is not only a neurotrophic
      factor, but also a natural angiogenesis inhibitor. This protein, as well as its
      biologically active fragments, possesses significant neuroprotective,
      neurotrophic, and antiangiogenic capabilities. The precise molecular mechanisms
      underpinning the effects of PEDF are still not quite clear. However, this protein
      generates great interest as a promising drug for the therapy of a wide range of
      neurodegenerative, ophthalmological, and oncological diseases. This review is a
      summary of what is known today about the structural features, biochemical
      properties, and multimodal functions of PEDF.

PMID- 22649651
TI  - Protein engineering of penicillin acylase.
AB  - Penicillin acylases (PA) are widely used for the production of semi-synthetic
      beta-lactam antibiotics and chiral compounds. In this review, the latest
      achievements in the production of recombinant enzymes are discussed, as well as
      the results of PA type G protein engineering.

PMID- 22649654
TI  - Adaptive Changes in Mycobacterium avium Gene Expression Profile Following
      Infection of Genetically Susceptible and Resistant Mice.
AB  - We performed a comparative analysis ofMycobacterium aviumtranscriptomes (strain
      724R) in infected mice of two different strains- resistant and susceptible to
      infection. Sets of mycobacterial genes transcribed in lung tissue were defined,
      and differentially transcribed genes were revealed. Our results indicate thatM.
      aviumgenes coding for enzymes of the Krebs cycle, oxidative phosphorylation, NO
      reduction, fatty acid biosynthesis, replication, translation, and genome
      modification are expressed at high levels in the lungs of genetically susceptible
      mice. The expression of genes responsible for cell wall properties, anaerobic
      nitrate respiration, fatty acid degradation, synthesis of polycyclic fatty acid
      derivatives, and biosynthesis of mycobactin and other polyketides is increased in
      the resistant mice. In the resistant host environment,Mycobacterium
      aviumapparently transitions to a latent state caused by the deficiency in
      divalent cations and characterised by anaerobic respiration, degradation of fatty
      acids, and modification of cell wall properties.

PMID- 22649655
TI  - Fingerprint-like Analysis of "Nanoantibody" Selection by Phage Display Using Two
      Helper Phage Variants.
AB  - This paper discusses the selection of mini-antibody (nanoantibody, nanobody(r) or
      single domain antibody) sequences of desired specificity by phage display-based
      method using a generated library of antigen-binding domains of special heavy
      chain only antibodies (single-stranded antibodies) of immunized camel. A
      comprehensive comparison of the efficiency of parallel selection procedures was
      performed by using the traditional (M13KO7) and modified (with N-terminal
      deletion in the surface gIII protein) helper phages. These two methods are partly
      complementary, and by using them in parallel one can significantly improve the
      selection efficiency. Parallel restriction analysis (fingerprinting) of PCR
      amplified cloned sequences coding for mini-antibodies (HMR-analysis) is proposed
      for identifying individual clones, as a replacement to sequencing (to a certain
      extent). Using this method, unique data were collected on the selection of mini
      antibody variants with the required specificity at various stages of a multi
      stage selection procedure. It has been shown that different sequences coding for
      mini-antibodies are selected in different ways, and that, if this feature is not
      taken into account, some mini-antibody variants may be lost.

PMID- 22649656
TI  - Regulation of store-operated channels by scaffold proteins in a431 cells.
AB  - Store-operated channels are major calcium influx pathways in nonexitable cells.
      Homer scaffold proteins are well known for their role in regulating calcium
      signaling. Here we report on a detailed single-channel level characterization of
      native store-operated channels regulated by Homer scaffold proteins in A431
      carcinoma cells. By applying the single-channel patch-clamp technique, we found
      that different types of store-operated calcium channels have different
      sensitivities to Homer proteins.

PMID- 22649657
TI  - Oligonucleotide microarray for the identification of carbapenemase genes of
      molecular classes a, B, and d.
AB  - This work is a report on the development of a method of hybridization analysis on
      DNA microarrays for the simultaneous identification and typing of carbapenemase
      encoding genes. These enzymes are produced by the microorganisms that are
      responsible for causing infectious diseases. The method involves several steps,
      including DNA extraction from clinical samples and amplification of carbapenemase
      genes by multiplex PCR with simultaneous labelling by biotin. Following that,
      hybridization of the labeled PCR products with oligonucleotide probes immobilized
      on the surface of a nitrocellulose-based DNA microarray occurs. The biotin
      molecules attached to the DNA duplexes are detected by using conjugates of
      streptavidin-horseradish peroxidase, which is then quantified by colorimetric
      detection of the enzyme. We have designed the required oligonucleotide probes and
      optimized the conditions of the membrane microarray-based hybridization analysis.
      Our method allows to identify 7 types of carbapenemase genes belonging to the
      molecular classes A, B, and D, and it also allows additional typing into genetic
      subgroups. The microarrays have been tested with the control strains producing
      the carbapenemase genes which have been characterized by sequencing. The
      developed method of hybridization analysis was employed to investigate clinical
      strains ofPseudomonasspp. andAcinetobacterspp., which produce carbapenemases of
      different classes based on phenotypic testing. All strains ofAcinetobacter
      baumaniiresistant to carbapenems were producers of two carbapenemase OXA-type
      genes (OXA-51, in combination with OXA-23 (1 strain), OXA-40 (5 strains), or OXA
      58 (4 strains)). The metallo-beta-lactamase VIM-2 type gene was detected in
      allPseudomonas aeruginosastrains resistant to carbapenems. Testing of carbapenem
      sensitive strains did not detect any carbapenemase genes. The microarray method
      for the identification of carbapenemase genes is very accurate and highly
      productive. It can be employed in clinical microbiological laboratories for the
      identification and study of carbapenemase epidemiology.

PMID- 22649658
TI  - New Test System for Serine/Threonine Protein Kinase Inhibitors Screening: E. coli
      APHVIII/Pk25 design.
AB  - An efficient test system for serine/threonine protein kinase inhibitors screening
      has been developed based on theE. coliprotein system APHVIII/Pk25.
      Phosphorylation of aminoglycoside phosphotransferase VIII (APHVIII) by protein
      kinases enhances resistance of the bacterial cell to aminoglycoside antibiotics,
      e.g. kanamycin. Addition of protein kinase inhibitors prevents phosphorylation
      and increases cell sensitivity to kanamycin. We have obtained modifications of
      APHVIII in which phosphorylatable Ser146 was encompassed into the canonical
      autophosphorylation sequence ofStreptomyces coelicolorPk25 protein kinase. Mutant
      and wild-typeaphVIII were cloned intoE. coliwith the catalytic domain ofpk25. As
      a result of the expression of these genes, accumulation of corresponding proteins
      was clearly observed. Extracted from bacterial lysates, Pk25 demonstrated its
      ability to autophosphorylate. It was shown that variants ofE. colicontaining
      bothaphVIIIand rk25were more resistant to kanamycin than those carrying
      onlyaphVIII. Protein kinase inhibitors of the indolylmaleimide class actively
      inhibited Pk25 and reduced cell resistance to kanamycin. Modeling of APHVIII and
      Pk25 3D structures showed that pSer146 is an analog of phosphoserine in the
      ribose pocket of protein kinase A. Pk25 conformation was similar to that of RknB
      ofMycobacterium tuberculosis. Potential indolylmaleimide inhibitors were docked
      into the ATP-binding pocket of Pk25. The designed test system can be used for the
      primary selection of ATP-competitive small molecule protein kinase inhibitors.

PMID- 22649659
TI  - Individual Genome of the Russian Male: SNP Calling and a de novo Assembly of
      Unmapped Reads.
AB  - A somatic cell genome was recently resequenced for a patient with renal cancer.
      The data were submitted to the NCBI Sequence Read Archive under the accession
      number SRA012240. Here, we have performed SNP calling for the genome and compared
      it with several published genomes. We have found 2, 921, 724 SNPs, including 1,
      472, 679 newly described ones. Among them, 63, 462 SNPs have been mapped to the Y
      chromosome and, based on 18 markers, the genome has been ascribed to the R1a1a
      haplogroup predominant in Russian males. The mitochondrial haplogroup has been
      determined as U5a, which is also common in the European part of Russia. Short
      reads unmapped to the human genome were used for thede novoassembly of DNA
      sequences. This resulted in genome-specific contigs (more than 100 bp in length)
      with an overall length of 154 kbp (for GAII) and 4.7 kbp (for SOLiD).

PMID- 22649660
TI  - Genomes, populations and diseases: ethnic genomics and personalized medicine.
AB  - This review discusses the progress of ethnic genetics, the genetics of common
      diseases, and the concepts of personalized medicine. We show the relationship
      between the structure of genetic diversity in human populations and the varying
      frequencies of Mendelian and multifactor diseases. We also examine the population
      basis of pharmacogenetics and evaluate the effectiveness of pharmacotherapy,
      along with a review of new achievements and prospects in personalized genomics.

PMID- 22649661
TI  - Hereditary breast-ovarian cancer syndrome in Russia.
AB  - Hereditary breast-ovarian cancer syndrome contributes to as much as 5-7% of
      breast cancer (BC) and 10-15% of ovarian cancer (OC) incidence. Mutations in the
      "canonical" genesBRCA1andBRCA2occur in 20-30% of affected pedigrees. In addition
      toBRCA1andBRCA2 mutations, germ-line lesions in theCHEK2,NBS1, andPALB2genes also
      contribute to familial BC clustering. The epidemiology of hereditary breast
      ovarian cancer in Russia has some specific features. The impact of the "founder"
      effect is surprisingly remarkable: a single mutation,BRCA15382insC, accounts for
      the vast majority ofBRCA1defects across the country. In addition, there are two
      other recurrentBRCA1alleles:BRCA14153delA andBRCA1185delAG. BesidesBRCA1, in
      Russia breast cancer is often caused by germ-line alterations in
      theCHEK2andNBS1genes. In contrast toBRCA1andBRCA2, theCHEK2andNBS1heterozygosity
      does not significantly increase the OC risk. Several Russian breast cancer
      clinics recently started to investigate the efficacy of cisplatin in the therapy
      ofBRCA1-related cancers; initial results show a unique sensitivity ofBRCA1
      associated tumours to this compound.

PMID- 22649662
TI  - Dosage compensation of sex chromosome genes in eukaryotes.
AB  - Sex chromosome evolution is accompanied by significant divergence in morphology
      and gene content and results in most genes of one of the sex chromosomes being
      present in two dosages in one sex and in one dosage in the other. To eliminate
      the difference in the expression levels of these genes between sexes and to
      restore equal expression levels of the genes between sex chromosomes and
      autosomes, mechanisms of dosage compensation have appeared. Studies of three
      classical objects,Drosophila melanogaster,Caenorhabditis elegans, and mammals,
      have shown that dosage compensation of X-linked genes can be achieved through
      completely different chromosome-wide mechanisms. New data on sex chromosome gene
      expression demonstrating that many sex chromosome genes can be expressed at
      different levels in males and females were recently obtained from birds and
      butterflies. In this review, dosage compensation mechanisms inD. melanogaster,C.
      elegans, and mammals are considered and the data on sex chromosome gene
      expression in birds and butterflies, and their influence on our view of dosage
      compensation, are discussed.

PMID- 22649663
TI  - The Role of p66shc in Oxidative Stress and Apoptosis.
AB  - p66shcis a gene that regulates the level of reactive oxygen species (ROS),
      apoptosis induction, and lifespan in mammals. Miceknocked out forp66shchave a
      lifespan~30% longeranddemonstrate an enhanced resistance to oxidative stress and
      age-related pathologies such as hypercholesterolemia, ischemia, and
      hyperglycemia. In this respect, p66shc is a promising pharmacological target for
      the treatment of age-related diseases. In this review, an attempt has been made
      to survey and put to a critical analysis data concerning the involvement of
      p66shs in the different signaling pathways that regulate oxidative stress and
      apoptosis.

PMID- 22649664
TI  - Chromatin Diminution Process Regulates rRNA Gene Copy Number in Freshwater
      Copepods.
AB  - The results of quantitative PCR (qPCR) presented in the paper clearly demonstrate
      that the sixteen-fold genome reduction inCyclops kolensisduring chromatin
      diminution (from 15.3 pg to 0.98 pg) results in a dramatic decrease in ribosomal
      RNA gene copy numbers in the genome of a somatic cell line by more than two
      orders of magnitude. The results presented allow for the consideration of the
      chromatin diminution as a mechanism of rDNA copy number regulation.

PMID- 22649665
TI  - Association study of xenobiotic detoxication and repair genes with malignant
      brain tumors in children.
AB  - This study presents the results of research on DNA polymorphism in children with
      malignant brain tumors (172 patients, 183 in the control group). Genotyping was
      performed using an allele-specific tetraprimer reaction for the genes of the
      first (CYP1A1 (2 sites)) and second phases of xenobiotic detoxication (GSTM1,
      GSTT1, GSTP1, GSTM3), DNA repair genesXRCC1, XPD(2 sites),OGG1, as well
      asNOS1andMTHFR.The increased risk of disease is associated with a minor variant
      ofCYP1A1(606G) (p = 0.009; OR = 1.50) and a deletion variant ofGSTT1, (p = 0.013,
      OR = 1.96). Maximum disease risk was observed in carriers of double deletions
      inGSTT1-GSTM1(p = 0.017, OR = 2.42). The obtained results are discussed in
      reference to literary data on the risk of malignant brain tumor formation in
      children and adults.

PMID- 22649666
TI  - Modeling of the Full-Size 3D Structure of Human Chaperone Hsp70 and Study of Its
      Interdomain Interactions.
AB  - Hsp70 is a chaperone protein that participates in the folding of de novo
      synthesized proteins, protection of the hydrophobic regions of denaturated
      proteins, the regulation of apoptosis, the immune response, and several other
      cellular processes. Despite the large number of publications devoted to the
      functioning and structure of Hsp70, a reliable full-size 3D structure of this
      protein remains currently unavailable. Several probable full-size models of human
      Hsp70 have been constructed based on the structures of individual domains and
      their components from different organisms and using molecular modeling
      methodology. The stability of the obtained structures was studied using molecular
      dynamics. As a result of such an analysis, the most adequate model was selected.
      The model was built on the basis of Hsp70 elements fromBos
      TaurusandCaenorhabditis elegans. Using the method of steered molecular dynamics,
      the key salt bridges responsible for the interdomain interactions were
      identified: Arg171: Glu516 and Arg416: Glu218. Based on the performed molecular
      modeling, the scheme of the mechanism triggering ATP hydrolysis and leading to
      the separation of ATPase and the substrate-binding domains was proposed.

PMID- 22649667
TI  - Classification of g-quadruplex DNA on the basis of the quadruplex twist angle and
      planarity of g-quartets.
AB  - The present work is devoted to the analysis of the G-quadruplex DNA structure
      using the bioinformatics method. The interest towards quadruplex DNAs is
      determined by their involvement in the functioning of telomeres and onco
      promoters as well as by the possibility to create on their basis aptamers and
      nanostructures. Here, we present an algorithm for a general analysis of the
      polymorphism of the G-quadruplex structure from the data bank PDB using original
      parameters. 74 structures were grouped according to the following parameters: the
      number of DNA strands, the number of G-quartets, and the location and orientation
      of the connecting loops. Two quantitative parameters were used to describe the
      quadruplex structure: the twist angle between two adjacent quartets (analogous to
      that for the complementary pair in the duplex DNA) and the quartet planarity (an
      original parameter). The distribution patterns of these values are specific for
      each group of quadruplex structures and are dependent upon the type of connecting
      loops used (diagonal, lateral or propeller). The tetramolecular loopless parallel
      quadruplex was used as a comparison template. The lateral loops introduce the
      strongest distortion into the structure of quadruplexes: the values of the twist
      angles are the lowest and are not typical for the other quadruplex groups. The
      loops of the diagonal type introduce much weaker deformation into quadruplexes;
      the structures with propeller loops are characterized by the optimum geometry of
      G-quartets. Hence, the correlation between the twist angle and the tension in the
      structure of quadruplex DNA is revealed.

PMID- 22649668
TI  - Biopharmacology of enzyme conjugates: vasoprotective activity of supramolecular
      superoxide dismutase-chondroitin sulfate-catalase derivative.
AB  - Bienzyme conjugate was obtained by the covalent connection of superoxide
      dismutase with catalase through endothelial glycocalyx glycosaminoglycan -
      chondroitin sulfate (SOD-CHS-CAT). This SOD-CHS-CAT conjugate has vasoprotective
      activity in respect to platelet interactions, tonus of the ring arterial fragment
      of a rat blood vessel, as well as normalization of hemodynamic parameters in rats
      and rabbits in conditions of oxidative stress caused by the administration of
      hydrogen peroxide. The SOD-CHS-CAT conjugate had antiplatelet potential due to
      its antiaggregation action manifested through the combination of enzyme
      activities and an acquired supramolecular structure. The influence on arterial
      fragment tonus was equivalent for SOD and CAT in native and conjugated form.
      Blood pressure and heart rate were significant and effectively normalized with
      SOD-CHS-CAT conjugate in rats and rabbits (after hydrogen peroxide administration
      as a perturbance stimulus). We have discovered the possibility of using the
      antioxidant bienzyme conjugate in chronic prophylaxis. It is important for a real
      development of the oral form of the SOD-CHS-CAT conjugate. These results indicate
      that the development of enzyme conjugates can be medically significant, as a
      promising approach for the creation of new drugs.

PMID- 22649670
TI  - A novel approach to the development of anticarcinogenic vaccines.
AB  - Human exposure to chemical carcinogens is an important etiological factor in
      cancer diseases. In this article, we will discuss a new approach to the
      development of anticarcinogenic vaccines. The main task in our research was to
      select a benzo[a]pyrene immunomimetic peptide considered as a hapten-specific
      component. For this purpose, we synthesized carcinogen-protein conjugates and
      prepared mono- and polyclonal antibodies to benzo[a]pyrene. Phage display
      technology was used to select the benzo[a]pyrene immunomimetic peptide, followed
      by an evaluation of the immunological properties of the obtained peptide. The
      obtained benzo[a]pyrene immunomimetic peptide could only simulate chemical
      carcinogens in the frame of the pIII protein. As a result, we prepared a
      recombinant protein composed of the benzo[a]pyrene immunomimetic peptide and pIII
      encoding sequences. Using ELISA, we demonstrated that the recombinant protein
      specifically interacts with the anti-benzo[a]pyrene monoclonal antibody (mAB B2).
      Using molecular modeling, we predicted the 3-D structure of the mAB B2 active
      center and analyzed the characteristics of its interaction with different
      polycyclic aromatic hydrocarbons, as well as with the benzo[a]pyrene
      immunomimetic peptide. Thus, a comprehensive analysis of the results of the
      obtainment of hapten-specific components of anticarcinogenic vaccines allowed us
      to outline a strategy for future development in this direction.

PMID- 22649669
TI  - "Prostate cancer proteomics" database.
AB  - A database of Prostate Cancer Proteomics has been created by using the results of
      a proteomic study of human prostate carcinoma and benign hyperplasia tissues, and
      of some human-cultured cell lines (PCP, http://ef.inbi.ras.ru). PCP consists of 7
      interrelated modules, each containing four levels of proteomic and biomedical
      data on the proteins in corresponding tissues or cells. The first data level,
      onto which each module is based, is a 2DE proteomic reference map where proteins
      separated by 2D electrophoresis, and subsequently identified by mass
      spectrometry, are marked. The results of proteomic experiments form the second
      data level. The third level contains protein data from published articles and
      existing databases. The fourth level is formed with direct Internet links to the
      information on corresponding proteins in the NCBI and UniProt databases. PCP
      contains data on 359 proteins in total, including 17 potential biomarkers of
      prostate cancer, particularly AGR2, annexins, S100 proteins, PRO2675, and
      PRO2044. The database will be useful in a wide range of applications, including
      studies of molecular mechanisms of the aetiology and pathogenesis of prostate
      diseases, finding new diagnostic markers, etc.

PMID- 22649671
TI  - Molecular and physiological mechanisms of membrane receptor systems functioning.
AB  - Molecular physiology is a new interdisciplinary field of knowledge that looks
      into how complicated biological systems function. The living cell is a relatively
      simple, but at the same time very sophisticated biological system. After the
      sequencing of the human genome, molecular physiology has endeavored to
      investigate the systems of cellular interactions at a completely new level based
      on knowledge of the spatial organization and functions of receptors, their
      ligands, and protein-protein interactions. In recent years, the achievements in
      molecular physiology have centered on the study of sensor reception mechanisms
      and intercellular data transfer, as well as the immune system physiology, amongst
      other processes.

PMID- 22649672
TI  - Quantum dots for molecular diagnostics of tumors.
AB  - Semiconductor quantum dots (QDs) are a new class of fluorophores with unique
      physical and chemical properties, which allow to appreciably expand the
      possibilities for the current methods of fluorescent imaging and optical
      diagnostics. Here we discuss the prospects of QD application for molecular
      diagnostics of tumors ranging from cancer-specific marker detection on
      microplates to non-invasive tumor imagingin vivo. We also point out the essential
      problems that require resolution in order to clinically promote QD, and we
      indicate innovative approaches to oncology which are implementable using QD.

PMID- 22649673
TI  - Assays for detection of telomerase activity.
AB  - Progressive loss of the telomeric ends of chromosomes caused by the semi
      conservative mechanism of DNA replication is an important timing mechanism which
      controls the number of cells doubling. Telomerase is an enzyme which elongates
      one chain of the telomeric DNA and compensates for its shortening during
      replication. Therefore, telomerase activity serves as a proliferation marker.
      Telomerase activity is not detected in most somatic cells, with the exception of
      embryonic tissues, stem cells, and reproductive organs. In most tumor cells (80
      90%), telomerase is activated and plays the role of the main instrument that
      supports the telomere length, which can be used for the diagnostics of neoplastic
      transformation. This is the primary reason why assays regarding the development
      of telomerase activity have attracted the attention of researchers. Telomerase
      activity testing may be useful in the search for telomerase inhibitors, which
      have the potential to be anti-cancer drugs. Moreover, telomerase activation may
      play a positive role in tissue regeneration; e.g., after partial removal of the
      liver or cardiac infarction. All telomerase activity detection assays can be
      divided into two large groups: those based on direct detection of telomerase
      products, and those based on different systems of amplification of the signals
      from DNA that yield from telomerase. The methods discussed in this review are
      suitable for testing telomerase activity in different samples: in protozoa and
      mammalian cells, mixed cellular populations, and tissues.

PMID- 22649674
TI  - Structural and dynamic study of the transmembrane domain of the amyloid precursor
      protein.
AB  - Alzheimer's disease affects people all over the world, regardless of nationality,
      gender or social status. An adequate study of the disease requires essential
      understanding of the molecular fundamentals of the pathogenesis. The amyloid beta
      peptide, which forms amyloid plaques in the brain of people with Alzheimer's
      disease, is the product of sequential cleavage of a single-span membrane amyloid
      precursor protein (APP). More than half of the APP mutations found to be
      associated with familial forms of Alzheimer's disease are located in its
      transmembrane domain. The pathogenic mutations presumably affect the structural
      dynamic properties of the APP transmembrane domain by changing its conformational
      stability and/or lateral dimerization. In the present study, the structure and
      dynamics of the recombinant peptide corresponding to the APP fragment, Gln686
      Lys726, which comprises the APP transmembrane domain with an adjacent N-terminal
      juxtamembrane sequence, were determined in the membrane mimetic environment
      composed of detergent micelles using NMR spectroscopy. The structure obtained in
      dodecylphosphocholine micelles consists of two alpha-helices: a short surface
      associated juxtamembrane helix (Lys687-Asp694) and a long transmembrane helix
      (Gly700-Leu723), both connected via a mobile loop region. A minor bend of the
      transmembrane alpha-helix is observed near the paired residues Gly708-Gly709. A
      cholesterol-binding hydrophobic cavity is apparently formed under the loop
      region, where the juxtamembrane alpha-helix comes into contact with the membrane
      surface near the N-terminus of the transmembrane alpha-helix.

PMID- 22649675
TI  - A In Vitro and In Vivo Study of the Ability of NOD1 Ligands to Activate the
      Transcriptional Factor NF-kB.
AB  - Pattern-recognition receptors (PRR) play a crucial role in the induction of the
      defense reactions of the immune system against pathogenic bacterial and viral
      infections. The activation of PRR by specific, highly conserved pathogen
      associated molecular patterns (PAMPs) induces numerous immune reactions related
      both to innate and adaptive immunity. In addition to the well-studied Toll-like
      receptors, pathogens can be recognized by the receptors belonging to the other
      PRR families; including NOD-like receptors (NLR). Stimulation of members of NOD
      like receptors (NOD1, 2) and Toll-like receptors results in the activation of the
      transcriptional factor NF-kB regulating gene expression in numerous molecules
      implicated in the development of proinflammatory reactions. As opposed to Toll
      like receptors, the NF-kB-activating ability of NLRs has not been fully studied.
      In this work, we examine the ability of one member of the NLR family - NOD1 - to
      activate the main proinflammatory transcriptional factor NF-kB. We also compare
      the NF-kB-activating ability of NOD1 ligands of a different structure with TLR4,5
      ligandsin vitroandin vivo.

PMID- 22649676
TI  - Family Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5,
      RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the
      central nervous system (CNS). Proteins of the immune system, as well as proteins
      that are involved in the infiltration of activated immune cells in the CNS, play
      an important role in the pathogenesis of MS. We investigated the association and
      linkage with MS of the following immune-system genes polymorphisms: HLA
      DRB1,CTLA4,TGFB1,IL4,CCR5 andRANTES, as well as of the matrix metalloproteinase 9
      (MMP9) and tissue inhibitor of metalloproteinase  1 (TIMP1) genes polymorphisms.
      For this purpose we used the transmission disequilibrium test (TDT). The group
      investigated was comprised of 100 nuclear families of Russian ethnicity, each
      consisting of an affected offspring and his nonaffected parents. It was found
      that HLA-DRB1*15alleleandMMP9*-1562C allele were transmitted from healthy
      heterozygous parents to affected children more frequently than alternative
      alleles (p  =  0.02 andp  =  0.04, respectively). Another family-based method,
      AFBAC (affected family-based control), showed MS association with HLA-DRB1*15,
      but not with theMMP9*-1562C allele.

PMID- 22649677
TI  - Comparative Bioinformatic Analysis of Active Site Structures in Evolutionarily
      Remote Homologues of alpha,beta-Hydrolase Superfamily Enzymes.
AB  - Comparative bioinformatic analysis is the cornerstone of the study of enzymes'
      structure-function relationship. However, numerous enzymes that derive from a
      common ancestor and have undergone substantial functional alterations during
      natural selection appear not to have a sequence similarity acceptable for a
      statistically reliable comparative analysis. At the same time, their active site
      structures, in general, can be conserved, while other parts may largely differ.
      Therefore, it sounds both plausible and appealing to implement a comparative
      analysis of the most functionally important structural elements - the active site
      structures; that is, the amino acid residues involved in substrate binding and
      the catalytic mechanism. A computer algorithm has been developed to create a
      library of enzyme active site structures based on the use of the PDB database,
      together with programs of structural analysis and identification of functionally
      important amino acid residues and cavities in the enzyme structure. The proposed
      methodology has been used to compare some alpha,beta-hydrolase superfamily
      enzymes. The insight has revealed a high structural similarity of catalytic site
      areas, including the conservative organization of a catalytic triad and oxyanion
      hole residues, despite the wide functional diversity among the remote homologues
      compared. The methodology can be used to compare the structural organization of
      the catalytic and substrate binding sites of various classes of enzymes, as well
      as study enzymes' evolution and to create of a databank of enzyme active site
      structures.

PMID- 22649678
TI  - Multi-walled Sarbon Nanotubes Penetrate into Plant Cells and Affect the Growth of
      Onobrychis arenaria Seedlings.
AB  - Engineered nanoparticles (ENPs) are now being used in many sectors of industry;
      however, the impact of ENPs on the environment still requires further study,
      since their use, recycling, and accidental spill can result in the accumulation
      of nanoparticles in the atmosphere, soil, and water. Plants are an integral part
      of ecosystems; hence their interaction with ENPs is inevitable. It is important
      to understand the consequences of this interaction and assess its potential
      effects. The present research is focused on studying the effects of the
      industrial material Taunit, containing multi-walled carbon nanotubes (MWNTs), on
      plants, and testing of its ability to penetrate into plant cells and tissues.
      Taunit has been found to stimulate the growth of roots and stems and cause an
      increase in peroxidase activity inOnobrychis arenariaseedlings. Peroxidase
      activity increases with decreasing concentration of Taunit from 1,000 to 100
      mg/l. MWNTs from Taunit were detected in the cells and tissues of seedling roots
      and leaves, implying the ability of MWNTs to penetrate into roots and accumulate
      there, as well as their ability to be transported into seedling leaves. Thus, the
      changes in the physiological parameters of plants are associated not only with
      MWNT adsorption on the root surface, as previously believed, but also with their
      penetration, uptake and accumulation in the plant cells and tissues.

PMID- 22649679
TI  - Modeling myocardial infarction in mice: methodology, monitoring, pathomorphology.
AB  - Myocardial infarction is one of the most serious and widespread diseases in the
      world. In this work, a minimally invasive method for simulating myocardial
      infarction in mice is described in the Russian Federation for the very first
      time; the procedure is carried out by ligation of the coronary heart artery or by
      controlled electrocoagulation. As a part of the methodology, a series of
      anesthetic, microsurgical and revival protocols are designed, owing to which a
      decrease in the postoperational mortality from the initial 94.6 to 13.6% is
      achieved. ECG confirms the development of large-focal or surface myocardial
      infarction. Postmortal histological examination confirms the presence of necrosis
      foci in the heart muscles of 87.5% of animals. Altogether, the medical data allow
      us to conclude that an adequate mouse model for myocardial infarction was
      generated. A further study is focused on the standardization of the experimental
      procedure and the use of genetically modified mouse strains, with the purpose of
      finding the most efficient therapeutic approaches for this disease.

PMID- 22649680
TI  - Association of cytokine gene alleles with the inflammation of human periodontal
      tissue.
AB  - Gingivitis and periodontitis are chronic inflammatory diseases of the periodontal
      tissue in humans caused by both environmental and genetic factors. The human
      cytokine genes that regulate the immune response may play an important role in
      the development of these chronic inflammatory diseases. The aim of this study is
      to analyze the allele status of eight human cytokine genes and to associate it
      with the inflammation of periodontal tissue in humans. A total of 296 unrelated
      males of Russian origin were studied. A significant association of theIL1BandIL6
      minor alleles and gingivitis was found. In addition, we found a significant
      association of the OHI-S index with theIL18gene alleles. The influence of genetic
      factors on gingivitis may contribute to the understanding of the mechanisms of
      interaction between genetic and environmental factors in periodontal conditions,
      and to the identification of risk groups for effective prevention and treatment.

PMID- 22649681
TI  - Promoters with cancer cell-specific activity for melanoma gene therapy.
AB  - Melanoma is one of the most aggressive tumors. It develops from pigment-forming
      cells (melanocytes) and results in a high number of lethal outcomes. The use of
      genetic constructs with the ability to specifically kill melanoma cells, but not
      normal cells, might increase the lifespan of patients, as well as improve their
      quality of life. One of the methods to achieve a selective impact for therapeutic
      genes on cancer cells is to utilize a transcriptional control mechanism using
      promoters that are specifically activated only in cancerous cells. In this
      review, promoters of the genes that are preferentially expressed in melanoma
      cells are described. These promoters, and other highly melanoma-specific
      regulatory elements, reduce the unspecific expression of therapeutic genes in
      normal tissues. Moreover, cancer-specific promoters and their elements are
      advantageous for the development of universal anticancer drugs. Examples of the
      use of double promoters that have a high potential as instruments in cancer gene
      therapy are also given in this review.

PMID- 22649682
TI  - Posttranslational Modifications of Ribosomal Proteins in Escherichia coli.
AB  - A number of ribosomal proteins inEscherichia coliundergo posttranslational
      modifications. Six ribosomal proteins are methylated (S11, L3, L11, L7/L12, L16,
      and L33), three proteins are acetylated (S5, S18, and L7), and protein S12 is
      methylthiolated. Extra amino acid residues are added to protein S6. S-terminal
      amino acid residues are partially removed from protein L31. The functional
      significance of these modifications has remained unclear. These modifications are
      not vital to the cells, and it is likely that they have regulatory functions.
      This paper reviews all the known posttranslational modifications of ribosomal
      proteins inEscherichia coli. Certain enzymes responsible for the modifications
      and mechanisms of enzymatic reactions are also discussed.

PMID- 22649684
TI  - Characteristics of Populations of the Russian Federation over the Panel of
      Fifteen Loci Used for DNA Identification and in Forensic Medical Examination.
AB  - Seventeen population groups within the Russian Federation were characterized for
      the first time using a panel of 15 genetic markers that are used for DNA
      identification and in forensic medical examinations. The degree of polymorphism
      and population diversity of microsatellite loci within the Power Plex system
      (Promega) in Russian populations; the distribution of alleles and genotypes
      within the populations of six cities and 11 ethnic groups of the Russian
      Federation; the levels of intra- and interpopulation genetic differentiation of
      population; genetic relations between populations; and the identification and
      forensic medical characteristics of the system of markers under study were
      determined. Significant differences were revealed between the Russian populations
      and the U.S. reference base that was used recently in the forensic medical
      examination of the RF. A database of the allelic frequencies of 15 microsatellite
      loci that are used for DNA identification and forensic medical examination was
      created; the database has the potential of becoming the reference for performing
      forensic medical examinations in Russia. The spatial organization of genetic
      diversity over the panel of the STR markers that are used for DNA identification
      was revealed. It represents the general regularities of geographical
      clusterization of human populations over various types of genetic markers. The
      necessity to take into account a population's genetic structure during forensic
      medical examinations and DNA identification of criminal suspects was
      substantiated.

PMID- 22649685
TI  - N-terminal moiety of Antimicrobial peptide Ltc1-k increases its toxicity for
      eukaryotic cells.
AB  - The antimicrobial peptide Ltc1-K and its derivates without one, two, then three N
      terminal amino acid residues were studied based on the hypothesis (backed by some
      experimental data) that the hydrophobic N-terminal moiety of linear cationic
      antimicrobial peptides defines their haemolytic activity. It was discovered that
      the excision of three N-terminal amino acid residues considerably decreases the
      peptide's toxicity for eukaryotic cells and simultaneously increases the
      selectivity of antibacterial activity for some bacteria species. Studies
      performed with the model membrane systems and human erythrocytes revealed that
      the main reason for the observed effect is a multifold decrease in the peptide's
      affinity to an eukaryotic cellular membrane enriched with zwitterionic
      phospholipids.

PMID- 22649686
TI  - Reconstruction of Purine Metabolism in Bacillus subtilis to Obtain the Strain
      Producer of AICAR: A New Drug with a Wide Range of Therapeutic Applications.
AB  - AICAR is a natural compound, an analogue and precursor of adenosine. As activator
      of AMP-activated protein kinase (AMPK), AICAR has a broad therapeutic potential,
      since it normalizes the carbohydrate and lipid metabolism and inhibits the
      proliferation of tumor cells. The synthesis of AICAR inBacillus subtiliscells is
      controlled by the enzymes of purine biosynthesis; their genes constituting purine
      operon (pur-operon). Reconstruction of purine metabolism inB. subtiliswas
      performed to achieve overproduction of AICAR. For this purpose, the genepurH,
      which encodes formyltransferase/IMP-cyclohydrolase, an enzyme that controls the
      conversion of AICAR to IMP, was removed from theB. subtilisgenome, ensuring the
      accumulation of AICAR. An insertion inactivating the genepurRthat encodes the
      negative transcriptional regulator of the purine biosynthesis operon was
      introduced into theB.subtilischromosome in order to boost the production of
      AICAR; the transcription attenuator located in the leader sequence ofpur-operon
      was deleted. Furthermore, the expression integrative vector carrying a strong
      promoter of therpsFgene encoding the ribosomal protein S6 was designed. The
      heterologousEscherichia coligenepurFencoding the first enzyme of the biosynthesis
      of purines with impaired allosteric regulation, as well as the
      modifiedE.coligeneprsresponsible for the synthesis of the precursor of purines -
      phosphoribosyl pyrophosphate (PRPP) - was cloned into this vector under the
      control of therpsFgene promoter. The modifiedpurFandprsgenes were inserted into
      the chromosome of theB. subtilisstrain.B. subtilisstrain obtained by these
      genetic manipulations accumulates 11-13 g/L of AICAR in the culture fluid.

PMID- 22649683
TI  - Gold nanoparticles in biology and medicine: recent advances and prospects.
AB  - Functionalized gold nanoparticles with controlled geometrical and optical
      properties are the subject of intensive studies and biomedical applications,
      including genomics, biosensorics, immunoassays, clinical chemistry, laser
      phototherapy of cancer cells and tumors, the targeted delivery of drugs, DNA and
      antigens, optical bioimaging and the monitoring of cells and tissues with the use
      of state-of-the-art detection systems. This work will provide an overview of the
      recent advances and current challenges facing the biomedical application of gold
      nanoparticles of various sizes, shapes, and structures. The review is focused on
      the application of gold nanoparticle conjugates in biomedical diagnostics and
      analytics, photothermal and photodynamic therapies, as a carrier for delivering
      target molecules, and on the immunological and toxicological properties. Keeping
      in mind the huge volume and high speed of the data update rate, 2/3 of our
      reference list (certainly restricted to 250 Refs.) includes publications
      encompassing the past 5 years.

PMID- 22649687
TI  - Dimeric structure of the transmembrane domain of glycophorin a in lipidic and
      detergent environments.
AB  - Specific interactions between transmembrane alpha-helices, to a large extent,
      determine the biological function of integral membrane proteins upon normal
      development and in pathological states of an organism. Various membrane-like
      media, partially those mimicking the conditions of multicomponent biological
      membranes, are used to study the structural and thermodynamic features that
      define the character of oligomerization of transmembrane helical segments. The
      choice of the composition of the membrane-mimicking medium is conducted in an
      effort to obtain a biologically relevant conformation of the protein complex and
      a sample that would be stable enough to allow to perform a series of long-term
      experiments with its use. In the present work, heteronuclear NMR spectroscopy and
      molecular dynamics simulations were used to demonstrate that the two most widely
      used media (detergent DPC micelles and lipid DMPC/DHPC bicelles) enable to
      perform structural studies of the specific interactions between transmembrane
      alpha-helices by the example of dimerizing the transmembrane domain of the
      bitopic protein glycophorin A. However, a number of peculiarities place lipid
      bicelles closer to natural lipid bilayers in terms of their physical properties.

PMID- 22649688
TI  - Relationship between the Pathogenic Representatives of Periodontal Pockets
      Microbiocenosis in Patients with Periodontitis with Varying Degrees of Severity.
AB  - Periodontitis is a common disease that is considered to be a manifestation of the
      distortion of the ratio between the normal and conditionally pathogenic
      microflora of periodontal pockets. In this study, the ratio between the six most
      important periodontal pathogens and the total microflora of the periodontal
      pocket in healthy individuals and patients with varying severity of periodontitis
      was ascertained by quantitative real-time PCR. It was ascertained that the
      relative content ofPorphyromonas gingivalis,Prevotella intermedia, andTannerella
      forsythensis(Bacteroides forsythus) persistently develops in the total microflora
      of the periodontal pocket upon progressing periodontitis; this value is higher
      than that in the control group by more than two orders of magnitude upon a severe
      degree of chronic generalized periodontitis.

PMID- 22649689
TI  - The Effects of beta (2) -Adrenoreceptor Activation on the Contractility, Ca
      Signals and Nitric Oxide Production in the Mouse Atria.
AB  - The effects of the selective beta(2)-adrenoreceptor agonist (fenoterol) on the
      functioning of mouse atrial were studied using both tensometry and fluorescent
      methods. It has been demonstrated that with the use of a high concentration of
      fenoterol (in the range of 1-50 uM), there is a more significant positive
      inotropic effect observed within a shorter period of time. In the case of
      relatively low doses of fenoterol (1 and 5 uM), its contractility effects are
      observed 20 min after the application of agonist, whereby in the case of high
      concentrations (25, 50 and 300 uM), the effects appear within the first minutes.
      During the first 10-15 min, 5 uM fenoterol causes an increase in the amplitude of
      Ca-signals in cardiomyocytes (this indicates an increase in the concentration of
      Ca ions during systole) and the activation of NO synthesis. However, after 20
      min, the production of NO decreases; while the amplitude of Ca-signals remains
      high. The application of 50 uM fenoterol leads to a rapid increase in the
      amplitude of Ca-signals: at the same time, it causes a decrease in the production
      of NO, which we found to begin to increase after 10 min of agonist application.
      It is suggested that the dynamics of the positive inotropic effect occurring
      under pharmacological stimulation of beta(2)-adrenoreceptors depend on the rate
      of increase in the amplitude of Ca-signals and on the degree of NO synthesis.

PMID- 22649690
TI  - Clinical Use of Inhibitors of HIV-1 Integration: Problems and Prospects.
AB  - The HIV-1 integrase enzyme is responsible for one of the key stages of retroviral
      replication; it acts as a catalyst for the integration of viral cDNA into the
      cell's genome. Inhibitors of HIV-1 integration have been under development for
      over 10 years; yet, only one integration inhibitor, raltegravir, has been
      approved for clinical use so far. Raltegravir binds two metal ions in the
      enzyme's active centre and blocks one of the integration stages: the strand
      transfer. Unfortunately, the clinical use of raltegravir results in the
      development of viral resistance among some patients. Several more HIV-1
      integration inhibitors are undergoing clinical trials at the moment. However, the
      structure and mechanism of action of those are similar to raltegravir, which
      results in the emergence of cross resistance with raltegravir. The present review
      is focused on the history of the development and clinical trials of raltegravir
      and its analogues, the problems connected with the emergence of viral resistance
      to integration inhibitors, and the prospect of their future clinical use.

PMID- 22649692
TI  - Characteristics of Artificial Virus-like Particles Assembled in vitro from Potato
      Virus X Coat Protein and Foreign Viral RNAs.
AB  - Potato virus X (PVX) and some other potexviruses can be reconstitutedin vitrofrom
      viral coat protein (CP) and RNA. PVX CP is capable of forming viral
      ribonucleoprotein complexes (vRNP) not only with homologous, but also with
      foreign RNAs. This paper presents the structure and properties of vRNP
      assembledin vitroupon incubation of PVX CP and RNAs of various plant and animal
      viruses belonging to different taxonomic groups. We have shown that the
      morphology and translational properties of vRNPs containing foreign
      (heterologous) RNA are identical to those of homological vRNP (PVX RNA - PVX CP).
      Our data suggest that the assembly of the "mixed" vRNPin vitrocould be started at
      the 5'-proximal region of the RNA, producing a helical structure of vRNPs with
      foreign nucleic acids. The formation of heterologous vRNPin vitrowith PVX CP
      appears not to require a specific 5' end RNA nucleotide sequence, and the PVX CP
      seems to be able to pack foreign genetic material of various sizes and
      compositions into artificial virus-like particles.

PMID- 22649691
TI  - Silencing of Her2, CCNB1 and PKC Genes by siRNA Results in Prolonged Retardation
      of Neuroblastoma Cell Division.
AB  - Deregulation of the expression of the genes that are involved in the control of
      the cell cycle impairs cellular differentiation and leads to cell death. This
      process can result in uncontrollable cell proliferation and, subsequently, cancer
      development. In this study, we examined the effect of the silencing of cancer
      related genes by small interfering RNAs (siRNA) targeted at mRNAof Her2, cyclin
      B1 (CCNB1), and protein kinase C(PKC) on the proliferation of human cancer cells
      of different origins. Maximum silencing ofCCNB1,Her2(in KB-3-1, SK-N-MC, MCF-7
      cells), andPKC(in MCF-7 cells) was achieved 72 h after transfection of the
      corresponding siRNAs, and 12 days after the transfection, the initial levels of
      the target mRNAs were fully recovered. Silencing ofHer2,CCNB1,andPKCdifferently
      effected the proliferation of the cell lines under study. The most pronounced
      antiproliferative action of the investigated siRNAs was observed in neuroblastoma
      SK-N-MC cells (3 - 10-fold reduction in the proliferation rate) even after the
      recovery of the initial levels of expression ofthe Her2,CCNB1, andPKS genes. The
      obtained data indicate that theCCNB1 andPKCgenes can be used as targets in the
      development of drugs for neuroblastoma treatment.

PMID- 22649693
TI  - Transcription Factor DLX5 As a New Target for Promising Antitumor Agents.
AB  - The crystal structure of the human transcription factor DLX5 has been used for
      the screening of a library consisting of 10(6 )compounds by the molecular docking
      technique.In vitro testsof the 14 top-rated ligands showed that compound Q12
      displays the best ability to inhibit the proliferation ofDlx5 positive mouse
      lymphoma cells, which correlates with the down-regulation ofc-mycexpression.
      Compound Q12 has low toxicity on normal human ovarian epithelial cells and mouse
      lymphoma cells with absent expression ofDlx5, and can be used for further
      chemical optimization and for the development of novel, highly efficient cancer
      treatments.

PMID- 22649694
TI  - Haplotype Diversity and Reconstruction of Ancestral Haplotype Associated with the
      c.35delG Mutation in the GJB2 (Cx26) Gene among the Volgo-Ural Populations of
      Russia.
AB  - The mutations in theGJB2(Sx26) gene make the biggest contribution to hereditary
      hearing loss. The spectrum and prevalence of theGJB2gene mutations are specific
      to populations of different ethnic origins. For severalGJB2 mutations, their
      origin from appropriate ancestral founder chromosome was shown, approximate
      estimations of "age" obtained, and presumable regions of their origin outlined.
      This work presents the results of the carrier frequencies' analysis of the major
      (for European countries) mutation c.35delG (GJB2gene) among 2,308 healthy
      individuals from 18 Eurasian populations of different ethnic origins: Bashkirs,
      Tatars, Chuvashs, Udmurts, Komi-Permyaks, Mordvins, and Russians (the Volga-Ural
      region of Russia); Byelorussians, Ukrainians (Eastern Europe); Abkhazians, Avars,
      Cherkessians, and Ingushes (Caucasus); Kazakhs, Uzbeks, Uighurs (Central Asia);
      and Yakuts, and Altaians (Siberia). The prevalence of the c.35delG mutation in
      the studied ethnic groups may act as additional evidence for a prospective role
      of the founder effect in the origin and distribution of this mutation in various
      populations worldwide. The haplotype analysis of chromosomes with the c.35delG
      mutation in patients with nonsyndromic sensorineural hearing loss (N=112) and in
      population samples (N =358) permitted the reconstruction of an ancestral
      haplotype with this mutation, established the common origin of the majority of
      the studied mutant chromosomes, and provided the estimated time of the c.35delG
      mutation carriers expansion (11,800 years) on the territory of the Volga-Ural
      region.

PMID- 22649695
TI  - Effective Genetic Expression of Nanoantibodies by Recombinant Adenoviral Vector
      in vitro.
AB  - The present study is devoted to the feasibility of expressing the single-domain
      mini-antibody (nanoantibody) selected from the library of sequences of the
      variable domains of special single-stranded antibodies derived from an immunized
      camel, a gene of which was introduced into eukaryotic cells within a recombinant
      adenoviral vector. A vector bearing the gene of a single-domain nanoantibody was
      obtained using the AdEasy Adenoviral Vector System (Stratagene). This method of
      delivering the nanoantibody gene facilitates efficient expression of this gene
      and functional activity of the nanoantibody. The results obtained can be used to
      produce passive immunizing tools against pathogens or new-generation
      immunobiological antitoxic medication.

PMID- 22649696
TI  - Rabin8 Protein Interacts with GTPase Rheb and Inhibits Phosphorylation of
      Ser235/Ser236 in Small Ribosomal Subunit Protein S6.
AB  - The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that in
      association with Raptor, mLST8, PRAS40 and Deptor forms a complex (mTORC1)
      playing the key role in the regulation of protein biosynthesis, transcription,
      cellular metabolism, apoptosis and autophagy; mainly via direct phosphorylation
      of S6 kinases. mTORC1 is activated by growth factors and amino acids via the
      activation of Rheb GTPase. In the current study, we demonstrate for the first
      time that the over-expression of Rabin8, which functions as a guanine nucleotide
      exchange factor for Rab8 GTPase, suppresses phosphorylation of Ser235/Ser236 in
      ribosomal protein S6. Downregulation of Rabin8 using small interfering RNA
      (siRNA) increases the phosphorylation of Ser235/Ser236 in ribosomal protein S6.
      Furthermore, Rabin8 can be immunoprecipitated with Rheb GTPase. These results
      suggest the existence of a novel mechanism of mTORS1 regulation and its
      downstream processes. Since Rabin8 is a known regulator of ciliogenesis, a
      potential link can exist between regulation of Rheb/mTORC1 and ciliogenesis.

PMID- 22649697
TI  - Bacterial Synthesis and Purification of Normal and Mutant Forms of Human FGFR3
      Transmembrane Segment.
AB  - The fibroblast growth factor receptor 3 (FGFR3) is a protein belonging to the
      family of receptor tyrosine kinases. FGFR3 plays an important role in human
      skeletal development. Mutations in this protein, including Gly380Arg or Ala391Glu
      substitutions in the transmembrane (TM) region, can cause different disorders in
      bone development. The determination of the spatial structure of the FGFR3 TM
      domain in a normal protein and in a protein with single Gly380Arg and Ala391Glu
      mutations is essential in order to understand the mechanisms that control
      dimerization and signal transduction by receptor tyrosine kinases. The effective
      system of expression of eukaryotic genes in bacteria and the purification
      protocol for the production of milligram amounts of both normal TM fragments of
      FGFR3 and those with single pathogenic mutations Gly380Arg and Ala391Glu, as well
      as their(15)N- and [(15)N,(13)C]-isotope-labelled derivatives, were described.
      Each peptide was produced inEscherichia coliBL21(DE3)pLysS cells as a C-terminal
      extension of thioredoxin A. The purification protocol involved immobilized metal
      affinity chromatography and cation- and anion-exchange chromatography, as well as
      the fusion protein cleavage with the light subunit of human enterokinase. The
      efficiency of the incorporation of target peptides into DPC/SDS and DPC/DPG
      micelles was confirmed using NMR spectroscopy. The described methodology of
      production of the native FGFR3 TM domain in norma and with single Gly380Arg and
      Ala391Glu mutations enables one to study their spatial structure using high
      resolution heteronuclear NMR spectroscopy.

PMID- 22649698
TI  - Recombinant Production of Horseradish Peroxidase Conjugates with Fab Antibodies
      in Pichia pastoris for Analytical Applications.
AB  - Recombinant immunoconjugates of marker enzymes with antigens or antibodies
      present considerably more advantages than those obtained by conventional methods
      of chemical synthesis; i.e. they are homogeneous, have a strictly determined
      stoichiometry, and retain the functional activity of both a marker protein and an
      antigen/antibody. Based on the pPICZalphaB shuttle vector, we first managed to
      obtain a recombinant conjugate of key marker enzyme horseradish peroxidase (HRP)
      withFabfragments of antibodies against atrazine. The resulting genetic
      construction allows us to switch to any other antibody sequence, via the simple
      re-cloning of variable parts and an additional reporter enzyme. Conjugates were
      successfully produced in thePichia pastorismethylotrophic yeast expression
      system. The target activity of the conjugates (both enzymatic and antigen
      binding) has been demonstrated by ELISA method.

PMID- 22649699
TI  - Atomic force microscopy study of the arrangement and mechanical properties of
      astrocytic cytoskeleton in growth medium.
AB  - Astrocytes are quite interesting to study because of their role in the
      development of various neurodegenerative disorders. The present work describes an
      examination of the arrangement and mechanical properties of cytoskeleton of
      living astrocytes using atomic force microscopy (AFM). The experiments were
      performed with an organotypic culture of dorsal root ganglia (DRG) obtained from
      a chicken embryo. The cells were cultivated on a gelatinous substrate and showed
      strong adhesion. AFM allows one to observe cytoskeleton fibers, which are
      interpreted as actin filaments and microtubules. This assumption is supported by
      confocal microscopy fluorescence imaging of alpha-tubulin and fibrillar actin.
      Mapping of the local Young's modulus of a living astrocyte showed that the stiff
      areas correspond to the sites where the cytoskeleton fibers are located. Thus,
      the data obtained indicate that AFM is a promising method to study neural cells
      cytoskeleton integrity and arrangement inin vitromodels of neurodegeneration.

PMID- 22649700
TI  - An Efficient Method for the Delivery of the Interleukin-2 Gene to Human
      Hematopoietic Cells using the ?Fiber-Modified Recombinant Adenovirus.
AB  - Recombinant human adenovirus serotype 5 (Ad5/35F-IL2) with modified fibres
      containing the C-terminal domain fiber-knob of human adenovirus serotype 35,
      carrying the gene of recombinant human IL-2, has been designed. As a result of
      the fiber modification, the adenovirus can efficiently deliver the genetic
      information to bone marrow leukocytes and the tumor blood cells KG-1A (human
      myeloblastic leukemia cells) and U937 (human histiocytic lymphoma cells), which
      are normally resistant to Ad5 infection. The flow cytometry data reveal that the
      modified Ad5/35F penetrates into a population of monocytes, granulocytes, and
      blast cells of human bone marrow. The expression of interleukin-2 in CAR-negative
      bone marrow leukocytes (3682.52 +/- 134.21 pg/ml) and the cell lines KG-1A (748.3
      +/- 32.8 pg/ml) and U937 (421.5 +/- 59.4 pg/ml) transduced with adenovirus
      Ad5/35F-IL2 is demonstrated. The fiber-modified adenovirus can be used as a
      vector for the efficient gene delivery of interleukin-2 to human normal and tumor
      hematopoietic cells.

PMID- 22649702
TI  - Mesenchymal stem cells in tissue growth and repair.
AB  - It has been established in the recent several decades that stem cells play a
      crucial role in tissue renewal and regeneration. Mesenchymal stem cells (MSCs)
      are part of the most important population of adult stem cells. These cells have
      hereby been identified for the very first time and subsequently isolated from
      bone marrow stroma. Bone marrow-derived MSCs have been believed to play the role
      of a source of cells for the renewal and repair of connective tissues, including
      bone, cartilage and adipose tissues. Cells similar to bone marrow-derived MSCs
      have now been identified in all postnatal tissues. Data on the distribution and
      function of MSCsin vivocollected using novel approaches pertaining to the
      identification of MSCsin situ, to their isolation from tissues, and finally to
      the determination of their biological properties have enabled successful revision
      of the role of MSCs in various organs and tissues. This review summarizes our
      own, as well as others', data concerning the role of MSCs in the regulation
      processes of tissue repair and regeneration. In our opinion, MSCs provide the
      connection between the blood-vascular, immune, endocrine, and nervous systems and
      tissue-specific stem cells in the body.

PMID- 22649701
TI  - Escort aptamers: new tools for the targeted delivery of therapeutics into cells.
AB  - Escort aptamers are DNA or RNA sequences with high affinity to certain cell
      surface proteins, which can be used for targeted delivery of various agents into
      cells of a definite type. The peculiarities of the selection of escort aptamers
      are discussed in this review. The methods used in selection of escort aptamers
      via the SELEX technique are considered, including selection against isolated cell
      surface proteins, cell fragments, living eukaryotic cells, and bacteria.
      Particular attention is given to the design and chemical modification of escort
      aptamers. The different fields of application of escort aptamers are described,
      including the targeted delivery of siRNAs, nanoparticles, toxins, and
      photoagents, as well as the identification of specific cell markers and the
      detection or isolation of cells of a definite type. The potential for the
      application of escort aptamers in the development of new therapeutic agents and
      diagnostic systems is also discussed.

PMID- 22649705
TI  - Behavior of Transplanted Multipotent Cells after in Vitro Transplantation into
      the Damaged Retina.
AB  - The use of stem cell technologies in retinal defect reparation therapy has
      produced beneficial results. Nowadays, numerous protocols exist which provide a
      neural differentiation of the stem cells transplanted into the retina. However,
      questions concerning the functional replacement of the missing retinal neurons by
      transplanted cells thus far remain unanswered. The organotypic culture protocol
      was used in this study in order to prove the possibility of transdifferentiation
      of bone marrow stromal cells (MMSCs) and neural stem/progenitor cells (NSPCs)
      from EGFP-positive mice and the functional integration of these cells. This
      technique enables a detailed characterization of cell behavior post
      transplantation. Using atomic force microscopy, we reliably demonstrated the
      difference (p < 0.01) between the thickness of the outgrowths formed by glial and
      endothelial retina cells and the thickness of neurites and neuro-like
      transplanted MMSC outgrowths. MMSCs are also shown to form synapses up to 2.5 +/-
      0.06 um in diameter on day 4 after the transplantation. Following electrical
      stimulation (20V, 0.5Hz, 200ms), clear depolarization of retinal neurons and
      their outgrowths is detected. It is shown that some of these GFP+ MMSCs, which
      changed their morphology after the transplantation in retinal explants to neuro
      like MMSCs, are capable of depolarizing after exogenous stimulation.

PMID- 22649704
TI  - Screening of Potential HIV-1 Inhibitors/Replication Blockers Using Secure
      Lentiviral in Vitro System.
AB  - The development and usage of safe cell systems for testing agents which possess
      anti-HIV activity is a very important factor in the design of new drugs. We have
      described in detail a system we designed that is based on lentiviral vectors
      (Prokofjeva et. al.,Antiviral Therapy,in print) for swift and completely safe
      screening of potential HIV-1 replication inhibitors. The system enables one to
      test the efficiency of the inhibitory activity of compounds whose action is
      directed towards either wild-type HIV-1 reverse transcriptase or integrase, or
      mutant enzymes corresponding to the drug-resistant virus form. Testing results of
      a number of already known drugs, which correlate well with published data as well
      as data on newly synthesized compounds, were obtained. Application of this system
      substantially broadens the possibilities of preclinical anti-HIV drugs testing.

PMID- 22649703
TI  - NAD (+) -dependent Formate Dehydrogenase from Plants.
AB  - NAD(+)-dependent formate dehydrogenase (FDH, EC 1.2.1.2) widely occurs in nature.
      FDH consists of two identical subunits and contains neither prosthetic groups nor
      metal ions. This type of FDH was found in different microorganisms (including
      pathogenic ones), such as bacteria, yeasts, fungi, and plants. As opposed to
      microbiological FDHs functioning in cytoplasm, plant FDHs localize in
      mitochondria. Formate dehydrogenase activity was first discovered as early as in
      1921 in plant; however, until the past decade FDHs from plants had been
      considerably less studied than the enzymes from microorganisms. This review
      summarizes the recent results on studying the physiological role, properties,
      structure, and protein engineering of plant formate dehydrogenases.

PMID- 22649707
TI  - Triggering of Toll-like Receptor-2 in Mouse Myelomonocytic Leukaemia Cells WEHI
      3B Leads to the Suppression of Apoptosis and Promotes Tumor Progression in Vivo.
AB  - Toll-like receptors are the essential components of innate immunity. It is shown
      that TLRs play an essential role in the immune resistance of an organism to
      bacterial and viral infections. The binding of TLR to its own ligands results in
      the activation of several adapter molecules and kinases, inducing the activation
      of the main pro-inflammatory transcriptional factors, which in turn induce the
      activation of the main pro-inflammatory transcriptional factors. This activation
      results in the development of both the innate immune response triggered by the
      enhanced expression of a number of pro-inflammatory cytokines and antimicrobial
      peptides and that of the adaptive immune response, via the activation of
      dendritic cells and enhancement of antigen presentation, etc. The ability of TLR
      agonists to bolster the immune reaction makes them promising for use in the
      therapy of infectious diseases and in the chemotherapy of malignant
      neoformations. However, different TLR ligands may have either antitumor activity
      (lipopolysaccharide, imiquimod, CpG) or, conversely, could beef up the resistance
      of tumor cells to apoptosis, stimulating their proliferation under certain
      conditions (lipopolysaccharide, lipopeptide). It has been shown that the TLR2
      dependent signalling pathway in the myelomonocytic mouse leukaemia cell line WEHI
      3B leads to the constitutive activation of the transcriptional factor NF-kB,
      suppression of apoptosis in tumor cells, and progression of myelomonocytic mouse
      leukaemiain vivo, upon the addition of TLR2 agonist (synthetic lipopeptide
      Pam2CSK4) or following the infection of tumor cells withMycoplasma arginini.

PMID- 22649706
TI  - New viral vector for superproduction of epitopes of vaccine proteins in plants.
AB  - The novel viral vectors PVX-CP AltMV and PVXdt-CP AltMV are superexpressors of
      the capsid protein (CP). These viral vectors were constructed on the basis of the
      potato virus X (PVX) genome andAlternantheramosaic virus (AltMV) CP gene. The
      expression, based on the hybrid viral vectors, is genetically safe, since the
      systemic transport and formation of infective viral particles are blocked. CP
      AltMV can self-assemble into virus-like particles (VLPs) in the absence of
      genomic RNA. The vectors can be used for the presentation of foreign peptides
      (including epitopes of human pathogens) on the surface of the VLP. The N-terminal
      extracellular domain (M2e) of the influenza virus A M2 protein and its truncated
      variant (DeltaM2e) were used as model heterologous peptides for the construction
      of the chimeric CP AltMV. Chimeric CP AltMV retains its ability to self-assemble
      into VLP. The epitopes of the M2 influenza virus protein were not eliminated
      during the process of accumulation, polymerization and purification of chimeric
      VLP AltMV, providing evidence of the stability of chimeric VLP with C-terminal
      heterologous epitopes. It appears that VLP produced by the vectors PVX-CP AltMV
      and PVXdt-CP AltMV can be used in the field of biotechnology for the presentation
      of the epitopes of vaccine proteins on their surfaces. The chimeric VLP AltMV
      with the presented foreign epitopes can be used as candidate vaccines.

PMID- 22649708
TI  - Inhibition of DNA gyrase by levofloxacin and related fluorine-containing
      heterocyclic compounds.
AB  - Fluoroquinolones are an important class of modern and efficient antibacterial
      drugs with a broad spectrum of activity. Levofloxacin (the optically active form
      of ofloxacin) is one of the most promising fluoroquinolone drugs, and its
      antibacterial activity is substantially higher than the activity of other drugs
      of the fluoroquinolone family. Earlier, in the Postovsky Institute of Organic
      Synthesis, UB RAS, an original method of levofloxacin synthesis was developed,
      and now the pilot batch of the drug is being prepared. Bacterial DNA gyrase is a
      specific target of fluoroquinolones; hence, the study of the enzyme-drug
      interaction is of theoretical and practical importance. Moreover, the parameters
      of DNA gyrase inhibition may serve as a criterion for drug quality. Here, we
      present the results of studying the interaction of DNA gyrase with a number of
      fluoroquinolones and their analogs: intermediates and semi-products of the
      levofloxacin synthesis, and also samples from the pilot batches of this drug. The
      importance of two structural elements of the levofloxacin molecule for the
      efficiency of the inhibition is revealed. The data obtained may be useful for the
      design of new drugs derived from levofloxacin.

PMID- 22649709
TI  - The Fate of the Nucleolus during Mitosis: Comparative Analysis of Localization of
      Some Forms of Pre-rRNA by Fluorescent in Situ Hybridization in NIH/3T3 Mouse
      Fibroblasts.
AB  - Nucleolus is the major structural domain of the cell nucleus, which in addition
      to proteins contains ribosomal RNA (rRNA) at different stages of maturation (or
      pre-rRNA). In mammals, the onset of mitosis is accompanied by the inhibition of
      rRNA synthesis, nucleolus disassembly, and the migration of pre-rRNA to the
      cytoplasm. However, the precise role of cytoplasmic pre-rRNA in mitosis remains
      unclear, and no comparative analysis of its different forms at consequent mitotic
      stages has thus far been performed. The focus of this research was the study of
      the localization of pre-rRNA in mitotic NIH/3T3 mouse fibroblasts by
      fluorescentin situhybridization (FISH) with probes to several regions of mouse
      primary 47S pre-rRNA transcripts and by confocal laser microscopy. The results
      reveal that all types of pre-rRNA appear in the cytoplasm at the beginning of
      mitosis, following the breakdown of the nucleolus and nuclear envelope. However,
      not all pre-rRNA are transported by chromosomes from maternal cells into daughter
      cells. At the end of mitosis, all types of pre-rRNA and 28S rRNA can be
      visualized in nucleolus-derived foci (NDF), structures containing many proteins
      of mature nucleoli the appearance of which indicates the commencement of
      nucleologenesis. However, early NDF are enriched in less processed pre-RNA,
      whereas late NDF contain predominantly 28S rRNA. Altogether, the results of this
      study strengthen the hypotheses that postulate that different forms of pre-rRNA
      may play various roles in mitosis, and that NDF can be involved in the maturation
      of pre-rRNA, remaining preserved in the cytoplasm of dividing cells.

PMID- 22649710
TI  - Effect of Sodium Chloride on Aggregation of Merocyanine 540 and Photosensitized
      Inactivation of Staphylococcus aureus and Pseudomonas aeruginosa.
AB  - Merocyanine 540 (MC540) is used as a photosensitizer for the inactivation of
      microorganisms. The following is already known about MC540: firstly, MC540 exists
      in distilled water in both monomeric and dimeric forms, and the addition of salts
      into a MC540 solution leads to the formation of large aggregates that can be
      detected by the resonance light scattering technique. Secondly, singlet oxygen
      can only be photogenerated by MC540 monomers. In the present work, we studied the
      effect of MC540 in the aggregated state on the rate of photosensitized
      inactivation ofStaphylococcus aureusandPseudomonas aeruginosa. To this end,
      bacteria either in MC540-containing distilled water or in a 0.25 M sodium
      chloride aqueous solution also containing MC540 are irradiated (546 nm). The
      results show that, in the presence of salt, the aggregation of MC540 greatly
      increases the efficiency of the MC540-photosensitized inactivation ofP.
      aeruginosaandS. aureus. In the presence of salt, the rates ofP. aeruginosaandS.
      aureusinactivation increase by factors of 10 and 30, respectively, in comparison
      with the rate of inactivation observed in the case of distilled water. Our
      results suggest that a salt-induced photosensitization mechanism can switch from
      the singlet oxygen to the free-radical pathway.

PMID- 22649711
TI  - Deficient Response to Experimentally Induced Alkalosis in Mice with the
      Inactivated insrr Gene.
AB  - Currently, the molecular mechanisms of the acid-base equilibrium maintenance in
      the body remain poorly understood. The development of alkalosis under various
      pathological conditions poses an immediate threat to human life. Understanding
      the physiological mechanisms of alkalosis compensation may stimulate the
      development of new therapeutic approaches and new drugs for treatment. It was
      previously shown that the orphan insulin receptor-related receptor (IRR) is
      activated by mildly alkaline media. In this study, we analyzed mutant mice with
      targeted inactivation of theinsrr gene encoding IRR, and revealed their phenotype
      related to disorders of the acid-base equilibrium. Higher concentrations of
      bicarbonate and CO(2)were found in the blood ofinsrr knockout mice in response to
      metabolic alkalosis.

PMID- 22649712
TI  - The Effect of Statins and Other Cardiovascular Medication on Ischemia-Reperfusion
      Damage in a Human DIEP Flap Model: Theoretical and Epidemiological
      Considerations.
AB  - Background. Statins and other cardiovascular medication possess antioxidant
      capacity. It was examined whether chronic use of these medications protects from
      the development of ischemia-reperfusion (I/R) related complications after DIEP
      (Deep Inferior Epigastric Perforator Free Flap) surgery. This paper contains a
      literature study on the antioxidant working mechanisms of these drugs. Methods.
      Medical information of 134 DIEP patients (173 flaps) was studied from their
      medical files. Patient and operative characteristics were registered, as well as
      I/R related complications. Results. Of the group that didnot use statins, 16.3%
      developed complications versus 30.8% amongst patients that did use these drugs (P
      = 0.29). Amongst patients that chronically use other cardiovascular medication,
      26.8% developed I/R related complications versus 14.4% of the patients without
      medication (P = 0.10). Conclusions. Chronic use of statins or other
      cardiovascular medication didnot decrease the occurrence of I/R related
      complications after DIEP surgery. Therefore, research should be aimed at
      evaluating short-term pre-treatment with statins.

PMID- 22649713
TI  - Erectile dysfunction and hypertension: impact on cardiovascular risk and
      treatment.
AB  - Erectile dysfunction (ED) is a common complaint in hypertensive men and can
      represent a systemic vascular disease, an adverse effect of antihypertensive
      medication or a frequent concern that may impair drug compliance. ED has been
      considered an early marker of cardiovascular disease. The connection between both
      conditions seems to be located in the endothelium, which may become unable to
      generate the necessary dilatation in penile vascular bed in response to sexual
      excitement, producing persistent impairment in erection. On the other hand, the
      real influence of antihypertensive drugs in erectile function still deserves
      discussion. Therefore, regardless of ED mechanism in hypertension, early
      diagnosis and correct approach of sexual life represent an important step of
      cardiovascular evaluation which certainly contributes for a better choice of
      hypertension treatment, preventing some complications and restoring the quality
      of life.

PMID- 22649714
TI  - The Relationship between Heart Rate Variability and Adiposity Differs for Central
      and Overall Adiposity.
AB  - While frank obesity is associated with reduced HRV, indicative of poorer
      autonomic nervous system (ANS) function, the association between body mass index
      (BMI) and HRV is less clear. We hypothesized that effects of adiposity on ANS are
      mostly mediated by visceral fat and less by subcutaneous fat; therefore,
      centrally distributed adipose tissue, that is, waist circumference (WC), should
      be more strongly associated with HRV than overall adiposity (BMI). To examine
      this hypothesis, we used data collected in a subset of the Baltimore Longitudinal
      Study of Aging to compare strength of association between HRV and WC to that of
      HRV and BMI. Time domain HRV variables SDNN (standard deviation of successive
      differences in normal-to-normal (N-N) intervals) and RMSSD (root mean square of
      successive differences in N-N intervals) were calculated from 24-hour Holter
      recordings in 159 participants (29-96 years). Increasing WC was associated with
      decreasing SDNN and RMSSD in younger but not older participants (P value for WC
      by-age interaction = 0.003). BMI was not associated with either SDNN or RMSSD at
      any age. In conclusion, central adiposity may contribute to sympathetic and
      parasympathetic ANS declines early in life.

PMID- 22649715
TI  - Echogenic Technology Improves Cannula Visibility during Ultrasound-Guided
      Internal Jugular Vein Catheterization via a Transverse Approach.
AB  - Objective. Echogenic technology has recently enhanced the ability of cannulas to
      be visualized during ultrasound-guided vascular access. We studied whether the
      use of an EC could improve visualization if compared with a nonechogenic vascular
      cannula (NEC) during real-time ultrasound-guided internal jugular vein (IJV)
      cannulation in the intensive care unit (ICU). Material and Methods. We
      prospectively enrolled 80 mechanically ventilated patients who required central
      venous access in a randomized study that was conducted in two medical-surgical
      ICUs. Forty patients underwent EC and 40 patients were randomized to NEC. The
      procedure was ultrasound-guided IJV cannulation via a transverse approach.
      Results. The EC group exhibited increased visibility as compared to the NEC group
      (88%  +/- 8% versus 20%  +/- 15%, resp. P < 0.01). There was strong agreement
      between the procedure operators and independent observers (k = 0.9; 95%
      confidence intervals assessed by bootstrap analysis = 0.87-0.95; P < 0.01).
      Access time (5.2 s +/- 2.5 versus 10.6 s +/- 5.7) and mechanical complications
      were both decreased in the EC group compared to the NEC group (P < 0.05).
      Conclusion. Echogenic technology significantly improved cannula visibility and
      decreased access time and mechanical complications during real-time ultrasound
      guided IJV cannulation via a transverse approach.

PMID- 22649716
TI  - Is routine ultrasound examination of the gallbladder justified in critical care
      patients?
AB  - Objective. We evaluated whether routine ultrasound examination may illustrate
      gallbladder abnormalities, including acute acalculous cholecystitis (AAC) in the
      intensive care unit (ICU). Patients and Methods. Ultrasound monitoring of the GB
      was performed by two blinded radiologists in mechanically ventilated patients
      irrespective of clinical and laboratory findings. We evaluated major (gallbladder
      wall thickening and edema, sonographic Murphy's sign, pericholecystic fluid) and
      minor (gallbladder distention and sludge) ultrasound criteria. Measurements and
      Results. We included 53 patients (42 males; mean age 57.6 +/- 2.8 years; APACHE
      II score 21.3 +/- 0.9; mean ICU stay 35.9 +/- 4.8 days). Twenty-five patients
      (47.2%) exhibited at least one abnormal imaging finding, while only six out of
      them had hepatic dysfunction. No correlation existed between liver biochemistry
      and ultrasound results in the total population. Three male patients (5.7%), on
      the grounds of unexplained sepsis, were diagnosed with AAC as incited by
      ultrasound, and surgical intervention was lifesaving. Patients who exhibited >=2
      ultrasound findings (30.2%) were managed successfully under the guidance of
      evolving ultrasound, clinical, and laboratory findings. Conclusions. Ultrasound
      gallbladder monitoring guided lifesaving surgical treatment in 3 cases of AAC;
      however, its routine application is questionable and still entails high levels of
      clinical suspicion.

PMID- 22649717
TI  - Increased extravascular lung water reduces the efficacy of alveolar recruitment
      maneuver in acute respiratory distress syndrome.
AB  - Introduction. In acute respiratory distress syndrome (ARDS) the recruitment
      maneuver (RM) is used to reexpand atelectatic areas of the lungs aiming to
      improve arterial oxygenation. The goal of our paper was to evaluate the response
      to RM, as assessed by measurements of extravascular lung water index (EVLWI) in
      ARDS patients. Materials and Methods. Seventeen adult ARDS patients were enrolled
      into a prospective study. Patients received protective ventilation. The RM was
      performed by applying a continuous positive airway pressure of 40 cm H(2)O for 40
      sec. The efficacy of the RM was assessed 5 min later. Patients were identified as
      responders if PaO(2)/FiO(2) increased by >20% above the baseline. EVLWI was
      assessed by transpulmonary thermodilution before the RM, and patients were
      divided into groups of low EVLWI (<10 mL/kg) and high EVLWI (>=10 mL/kg).
      Results. EVLWI was increased in 12 patients. Following RM, PaO(2)/FiO(2)
      increased by 33 (4-65) % in the patients with low EVLWI, whereas those in the
      high EVLWI group experienced a change by only -1((-13)-(+5)) % (P = 0.035).
      Conclusion. In ARDS, the response to a recruitment maneuver might be related to
      the severity of pulmonary edema. In patients with incresed EVLWI, the recruitment
      maneuver is less effective.

PMID- 22649718
TI  - Pulmonary Artery Catheter (PAC) Accuracy and Efficacy Compared with Flow Probe
      and Transcutaneous Doppler (USCOM): An Ovine Cardiac Output Validation.
AB  - Background. The pulmonary artery catheter (PAC) is an accepted clinical method of
      measuring cardiac output (CO) despite no prior validation. The ultrasonic cardiac
      output monitor (USCOM) is a noninvasive alternative to PAC using Doppler
      ultrasound (CW). We compared PAC and USCOM CO measurements against a gold
      standard, the aortic flow probe (FP), in sheep at varying outputs. Methods. Ten
      conscious sheep, with implanted FPs, had measurements of CO by FP, USCOM, and
      PAC, at rest and during intervention with inotropes and vasopressors. Results. CO
      measurements by FP, PAC, and USCOM were 4.0 +/- 1.2 L/min, 4.8 +/- 1.5 L/min, and
      4.0 +/- 1.4 L/min, respectively, (n = 280, range 1.9 L/min to 11.7 L/min).
      Percentage bias and precision between FP and PAC, and FP and USCOM was -17 and
      47%, and 1 and 36%, respectively. PAC under-measured Dobutamine-induced CO
      changes by 20% (relative 66%) compared with FP, while USCOM measures varied from
      FP by 3% (relative 10%). PAC reliably detected -30% but not +40% CO changes, as
      measured by receiver operating characteristic area under the curve (AUC), while
      USCOM reliably detected +/-5% changes in CO (AUC > 0.70). Conclusions. PAC
      demonstrated poor accuracy and sensitivity as a measure of CO. USCOM provided
      equivalent measurements to FP across a sixfold range of outputs, reliably
      detecting +/-5% changes.

PMID- 22649719
TI  - Neuromagnetic indication of dysfunctional emotion regulation in affective
      disorders.
AB  - Dysfunctional emotion regulation is often reported in affective disorders, but it
      is unclear whether this dysfunction concerns initial processing of emotional
      input or regulation of resulting emotion. The present study addressed these
      aspects in 27 depressive and 15 borderline personality disorder patients and 28
      healthy controls who were instructed to either passively view unpleasant and
      neutral pictures or downregulate emotional responses by reappraisal, while
      neuromagnetic brain activity was measured. All three groups showed more early
      response to unpleasant than to neutral pictures, whereas patients failed to show
      subsequent activity suppression under instructions to down-regulate. This
      deficient emotion regulation was evident primarily in those subjects reporting
      high childhood adversity. Results support intact emotional input processing but
      impaired emotion regulation in affective disorders and indicate a moderating
      influence of early life stress.

PMID- 22649720
TI  - Ductal carcinoma in situ: what can we learn from clinical trials?
AB  - Ductal Carcinoma in situ has been diagnosed more frequently in the last few years
      and now accounts for approximately one-fourth of all treated breast cancers.
      Traditionally, this disease has been treated with total mastectomy, but
      conservative surgery has become increasingly used in the absence of unfavourable
      clinical conditions, if a negative excision margin can be achieved. It is
      controversial whether subgroups of patients with favourable in situ tumors could
      be managed by conservative surgery alone, without radiation. As the disease is
      diagnosed more frequently in younger patients, these issues are very relevant,
      and much research has focused on this topic in the last two decades. We reviewed
      randomized trials regarding adjuvant radiation after breast-conservative surgery
      and compared data with available retrospective studies.

PMID- 22649721
TI  - A critique of the undergraduate nursing preceptorship model.
AB  - The preceptorship model is a cornerstone of clinical undergraduate nursing
      education in Canadian nursing programs. Their extensive use means that nursing
      programs depend heavily on the availability and willingness of Registered Nurses
      to take on the preceptor role. However, both the health service and education
      industries are faced with challenges that seem to undermine the effectiveness of
      the preceptorship clinical model. Indeed, the unstable nature of the clinical
      setting as a learning environment in conjunction with faculty shortages and
      inadequate preparation for preceptors and supervising faculty calls us to
      question if the preceptorship model is able to meet student learning needs and
      program outcomes. In a critical analysis of preceptorship, we offer a
      deconstruction of the model to advance clinical nursing education discourse.

PMID- 22649722
TI  - Single-incision laparoscopic cholecystectomy: is it a plausible alternative to
      the traditional four-port laparoscopic approach?
AB  - The current standard-of-care for treatment of cholecystectomy is the four port
      laparoscopic approach. The development of single incision/laparoendoscopic single
      site surgery (SILC/LESS) has now led to the development of new techniques for
      removal of the gallbladder. The use of SILC/LESS is now currently being evaluated
      as the next step in treatment of cholecystectomy. This review is an attempt to
      consolidate the current knowledge and analyze the feasibility of world-wide
      implementation of SILC/LESS.

PMID- 22649723
TI  - A Bioinformatics Resource for TWEAK-Fn14 Signaling Pathway.
AB  - TNF-related weak inducer of apoptosis (TWEAK) is a new member of the TNF
      superfamily. It signals through TNFRSF12A, commonly known as Fn14. The TWEAK-Fn14
      interaction regulates cellular activities including proliferation, migration,
      differentiation, apoptosis, angiogenesis, tissue remodeling and inflammation.
      Although TWEAK has been reported to be associated with autoimmune diseases,
      cancers, stroke, and kidney-related disorders, the downstream molecular events of
      TWEAK-Fn14 signaling are yet not available in any signaling pathway repository.
      In this paper, we manually compiled from the literature, in particular those
      reported in human systems, the downstream reactions stimulated by TWEAK-Fn14
      interactions. Our manual amassment of the TWEAK-Fn14 pathway has resulted in
      cataloging of 46 proteins involved in various biochemical reactions and TWEAK
      Fn14 induced expression of 28 genes. We have enabled the availability of data in
      various standard exchange formats from NetPath, a repository for signaling
      pathways. We believe that this composite molecular interaction pathway will
      enable identification of new signaling components in TWEAK signaling pathway.
      This in turn may lead to the identification of potential therapeutic targets in
      TWEAK-associated disorders.

PMID- 22649725
TI  - Handgrip maximal voluntary isometric contraction does not correlate with thenar
      motor unit number estimation.
AB  - In slowly progressive conditions, such as motor neurone disease (MND), 50-80% of
      motor units may be lost before weakness becomes clinically apparent. Despite
      this, maximal voluntary isometric contraction (MVIC) has been reported as a
      clinically useful, reliable, and reproducible measure for monitoring disease
      progression in MND. We performed a study on a group of asymptomatic subjects that
      showed a lack of correlation between isometric grip strength and thenar MUNE.
      Motor unit number estimation (MUNE) estimates the number of functioning lower
      motor neurones innervating a muscle or a group of muscles. We used the
      statistical electrophysiological technique of MUNE to estimate the number of
      motor units in thenar group of muscles in 69 subjects: 19 asymptomatic Cu, Zn
      superoxide dismutase 1 (SOD 1) mutation carriers, 34 family controls, and 16
      population controls. The Jamar hand dynamometer was used to measure isometric
      grip strength. This study suggests that MUNE is more sensitive for monitoring
      disease progression than maximal voluntary isometric contraction (MVIC), as MUNE
      correlates with the number of functional motor neurones. This supports the
      observation that patients with substantial chronic denervation can maintain
      normal muscle twitch tension until 50-80% of motor units are lost and weakness is
      detectable.

PMID- 22649724
TI  - In Vivo Consequences of Disrupting SH3-Mediated Interactions of the Inducible T
      Cell Kinase.
AB  - ITK-SH3-mediated interactions, both with exogenous ligands and via intermolecular
      self-association with ITK-SH2, have been shown to be important for regulation of
      ITK activity. The biological significance of these competing SH3 interactions is
      not completely understood. A mutant of ITK where substitution of the SH3 domain
      with that of the related kinase BTK (ITK-BTK((SH3))) was used to disrupt
      intermolecular self-association of ITK while maintaining canonical binding to
      exogenous ligands such as SLP-76. ITK-BTK((SH3)) displays reduced association
      with SLP-76 leading to inefficient transphosphorylation, reduced phosphorylation
      of PLCgamma1, and diminished Th(2) cytokine production. In contrast, ITK
      BTK((SH3)) displays no defect in its localization to the T-cell-APC contact site.
      Another mutation, Y511F, in the activation loop of ITK, impairs ITK activation. T
      cells expressing ITK-Y511F display defective phosphorylation of ITK and its
      downstream target PLCgamma1, as well as significant inhibition of Th(2)
      cytokines. In contrast, the inducible localization of ITK-Y511F to the T cell-APC
      contact site and its association with SLP-76 are not affected. The presented data
      lend further support to the hypothesis that precise interactions between ITK and
      its signaling partners are required to support ITK signaling downstream of the
      TCR.

PMID- 22649726
TI  - Left ventricular diastolic dysfunction in dialysis patients assessed by novel
      speckle tracking strain rate analysis: prevalence and determinants.
AB  - Background. Diastolic dysfunction is common among dialysis patients and is
      associated with increased morbidity and mortality. Novel echocardiographic
      speckle tracking strain analysis permits accurate assessment of left ventricular
      diastolic function, independent of loading conditions and taking all myocardial
      segments into account. The aim of the study was to evaluate the prevalence of
      diastolic dysfunction in chronic dialysis patients using this novel technique,
      and to identify its determinants among clinical and echocardiographic variables.
      Methods. Patients currently enrolled in the ICD2 study protocol were included for
      this analysis. Next to conventional echo measurements diastolic function was also
      assessed by global diastolic strain rate during isovolumic relaxation (SRIVR).
      Results. A total of 77 patients were included (age 67 +/- 8 years, 74% male).
      When defined as E/SRIVR >=236, the prevalence of diastolic dysfunction was higher
      compared to more conventional measurements (48% versus 39%). Left ventricular
      mass (OR 1.02, 95% CI 1.00-1.04, P = 0.014) and pulse wave velocity (OR 1.34, 95%
      CI 1.07-1.68, P = 0.01) were independent determinants of diastolic dysfunction.
      Conclusion. Diastolic dysfunction is highly prevalent among dialysis patients and
      might be underestimated using conventional measurements. Left ventricular mass
      and pulse wave velocity were the only determinants of diastolic dysfunction in
      these patients.

PMID- 22649727
TI  - TRIM22: A Diverse and Dynamic Antiviral Protein.
AB  - The tripartite motif (TRIM) family of proteins is an evolutionarily ancient group
      of proteins with homologues identified in both invertebrate and vertebrate
      species. Human TRIM22 is one such protein that has a dynamic evolutionary history
      that includes gene expansion, gene loss, and strong signatures of positive
      selection. To date, TRIM22 has been shown to restrict the replication of a number
      of viruses, including encephalomyocarditis virus (EMCV), hepatitis B virus (HBV),
      and human immunodeficiency virus type 1 (HIV-1). In addition, TRIM22 has also
      been implicated in cellular differentiation and proliferation and may play a role
      in certain cancers and autoimmune diseases. This comprehensive paper summarizes
      our current understanding of TRIM22 structure and function.

PMID- 22649728
TI  - Measurement of harm outcomes in older adults after hospital discharge:
      reliability and validity.
AB  - Objectives. Defining and validating a measure of safety contributes to further
      validation of clinical measures. The objective was to define and examine the
      psychometric properties of the outcome "incidents of harm." Methods. The Incident
      of Harm Caregiver Questionnaire was administered to caregivers of older adults
      discharged from hospital by telephone. Caregivers completed daily logs for one
      month and medical charts were examined. Results. Test-retest reliability (n = 38)
      was high for the occurrence of an incident of harm (yes/no; kappa = 1.0) and the
      type of incident (agreement = 100%). Validation against daily logs found no
      disagreement regarding occurrence or types of incidents. Validation with medical
      charts found no disagreement regarding incident occurrence and disagreement in
      half regarding incident type. Discussion. The data support the Incident of Harm
      Caregiver Questionnaire as a reliable and valid estimation of incidents for this
      sample and are important to researchers as a method to measure safety when
      validating clinical measures.

PMID- 22649729
TI  - Total joint replacement in the past does not relate to a deteriorated functional
      level and health status in the oldest old.
AB  - Total hip or knee replacement is effective in improving joint function, quality
      of life, and pain reduction. The oldest old population with joint replacements
      (TJR) is underrepresented in current literature. We compared health-related and
      functional characteristics of oldest olds with and without TJR. Participants
      (aged 85 years) were divided into a group with and without TJR. Comorbidity,
      physical and joint functioning, daily living activities, quality of life, and
      mortality were recorded. Thirty-eight of 599 participants (6.3%) received a TJR
      in the past. Participants with a TJR had slightly less comorbidities, walked
      slower (P = 0.006), and complained more about hip-pain (P = 0.007). Mortality of
      those with a TJR was lower during the first 8-year followup (P = 0.04). All other
      characteristics were comparable between groups. We conclude that subjects with a
      TJR performed equally well, besides showing a lower gait speed and a higher
      frequency of hip-pain. Except for the lower gaitspeed, having a TJR is not
      associated with poorer health.

PMID- 22649730
TI  - TCTP in development and cancer.
AB  - The translationally controlled tumor protein (TCTP) is highly conserved among
      animal species. It is widely expressed in many different tissues. It is involved
      in regulating many fundamental processes, such as cell proliferation and growth,
      apoptosis, pluripotency, and the cell cycle. Hence, it is not surprising that it
      is essential for normal development and, if misregulated, can lead to cancer.
      Provided herein is an overview of the diverse functions of TCTP, with a focus on
      development. Furthermore, we discuss possible ways by which TCTP misregulation or
      mutation could result in cancer.

PMID- 22649731
TI  - Staurosporine inhibits frequency-dependent myofilament desensitization in intact
      rabbit cardiac trabeculae.
AB  - Myofilament calcium sensitivity decreases with frequency in intact healthy rabbit
      trabeculae and associates with Troponin I and Myosin light chain-2
      phosphorylation. We here tested whether serine-threonine kinase activity is
      primarily responsible for this frequency-dependent modulations of myofilament
      calcium sensitivity. Right ventricular trabeculae were isolated from New Zealand
      White rabbit hearts and iontophoretically loaded with bis-fura-2. Twitch force
      calcium relationships and steady state force-calcium relationships were measured
      at frequencies of 1 and 4 Hz at 37  degrees C. Staurosporine (100 nM), a
      nonspecific serine-threonine kinase inhibitor, or vehicle (DMSO) was included in
      the superfusion solution before and during the contractures. Staurosporine had no
      frequency-dependent effect on force development, kinetics, calcium transient
      amplitude, or rate of calcium transient decline. The shift in the pCa(50) of the
      force-calcium relationship was significant from 6.05 +/- 0.04 at 1 Hz versus 5.88
      +/- 0.06 at 4 Hz under control conditions (vehicle, P < 0.001) but not in
      presence of staurosporine (5.89 +/- 0.08 at 1 Hz versus 5.94 +/- 0.07 at 4 Hz, P
      = NS). Phosphoprotein analysis (Pro-Q Diamond stain) confirmed that staurosporine
      significantly blunted the frequency-dependent phosphorylation at Troponin I and
      Myosin light chain-2. We conclude that frequency-dependent modulation of calcium
      sensitivity is mediated through a kinase-specific effect involving
      phosphorylation of myofilament proteins.

PMID- 22649732
TI  - Tulsa oklahoma oktoberfest tent collapse report.
AB  - Background. On October 17, 2007, a severe weather event collapsed two large tents
      and several smaller tents causing 23 injuries requiring evacuation to emergency
      departments in Tulsa, OK. Methods. This paper is a retrospective analysis of the
      regional health system's response to this event. Data from the Tulsa Fire
      Department, The Emergency Medical Services Authority (EMSA), receiving hospitals
      and coordinating services were reviewed and analyzed. EMS patient care reports
      were reviewed and analyzed using triage designators assigned in the field, injury
      severity scores, and critical mortality. Results. EMT's and paramedics from Tulsa
      Fire Department and EMSA provided care at the scene under unified incident
      command. Of the 23 patients transported by EMS, four were hospitalized, one with
      critical spinal injury and one with critical head injury. One patient is still in
      ongoing rehabilitation. Discussion. Analysis of the 2007 Tulsa Oktoberfest mass
      casualty incident revealed rapid police/fire/EMS response despite challenges of
      operations at dark under severe weather conditions and the need to treat a
      significant number of injured victims. There were no fatalities. Of the patients
      transported by EMS, a minority sustained critical injuries, with most sustaining
      injuries amenable to discharge after emergency department care.

PMID- 22649733
TI  - Subcutaneous fluid administration: a potentially useful tool in prehospital care.
AB  - Mass casualty incidents (MCIs) and disaster medical situations are ideal settings
      in which there is need for a novel approach to infusing fluids and medications
      into a patient's intravascular space. An attractive new approach would avoid the
      potentially time-consuming needlestick and venous cannulation requiring a trained
      practitioner. In multiple-patient situations, trained practitioners are not
      always available in sufficient numbers to enable timely placement of intravenous
      catheters. The novel approach for intravascular space infusion, described in this
      paper involves the preadministration of the enzyme, human recombinant
      hyaluronidase (HRH), into the subcutaneous (SC) space, via an indwelling
      catheter. The enzyme "loosens" the SC space effectively enhancing the absorption
      of fluids and medication.

PMID- 22649734
TI  - Is there truly no benefit with sunscreen use and Basal cell carcinoma? A critical
      review of the literature and the application of new sunscreen labeling rules to
      real-world sunscreen practices.
AB  - Basal cell carcinoma (BCC) is the most common human malignancy. Both
      epidemiological and direct evidence have established ultraviolet (UV) exposure
      from the sun as the most important risk factor for BCC development. There has
      only been one randomized and controlled study to examine sunscreen's role in the
      prevention of BCC, and no significant protective benefit was found. This study
      did not address four important concepts: sunscreen abuse, sunscreen misuse,
      sunscreen formulation, and cumulative UV exposure. Thus, the results of this
      study are difficult to interpret and extrapolate with real-world sunscreen
      practices.

PMID- 22649735
TI  - Histological, immunohistological, and clinical features of merkel cell carcinoma
      in correlation to merkel cell polyomavirus status.
AB  - Merkel cell carcinoma is a rare, but highly malignant tumor of the skin with high
      rates of metastasis and poor survival. Its incidence rate rises and is currently
      about 0.6/100000/year. Clinical differential diagnoses include basal cell
      carcinoma, cyst, amelanotic melanoma, lymphoma and atypical fibroxanthoma. In
      this review article clinical, histopathological and immunhistochemical features
      of Merkel cell carcinoma are reported. In addition, the role of Merkel cell
      polyomavirus is discussed.

PMID- 22649736
TI  - Optimization of the Nutritional Parameters for Enhanced Production of B. subtilis
      SPB1 Biosurfactant in Submerged Culture Using Response Surface Methodology.
AB  - Nutritional requirements can contribute considerably to the production cost and
      the bioprocess economics. Media optimisation using response surface methodology
      is one of the used methods to ameliorate the bioprocess economics. In the present
      study, biosurfactant production by Bacillus subtilis SPB1 was effectively
      enhanced by response surface methodology. A Plackett-Burman-based statistical
      screening procedure was adopted to determine the most important factor affecting
      lipopeptide production. Eleven variables are screened and results show that
      glucose, K(2)HPO(4), and urea concentrations influence the most biosurfactant
      production. A Central Composite Design was conducted to optimize the three
      selected factors. Statistical analyses of the data of model fitting were done by
      using NemrodW. Results show a maximum predicted biosurfactant concentration of
      2.93 (+/-0.32) g/L when using 15 g/L glucose, 6 g/L urea, and 1 g/L K(2)HPO(4).
      The predicted value is approximately 1.65 much higher than the original
      production determined by the conventional one-factor-at-a-time optimization
      method.

PMID- 22649738
TI  - Triple-negative breast cancer.

PMID- 22649737
TI  - Mechanisms of Resistance to Trastuzumab and Novel Therapeutic Strategies in HER2
      Positive Breast Cancer.
AB  - HER2-positive breast cancers have poorer prognosis and are prime candidates for
      molecular-targeted therapy because they are driven by the unique mechanism of
      HER2 oncogene addiction. While anti-HER2 agents such as trastuzumab and lapatinib
      are integral to the treatment of HER2-positive breast cancer, intrinsic and
      secondary resistance pose a significant challenge, underscoring the need to
      develop novel anti-HER2 therapies. In recent years, an array of promising and
      novel anti-HER2 therapeutic agents and their combinations have entered various
      stages of clinical development. However, questions remain on the optimal
      sequences of HER2-directed therapies and selection of patients for the most
      appropriate drug or combinations; incompletely defined mechanisms of trastuzumab
      action and resistance have also dampened the progress of more successful
      biomarker-driven treatment approaches. This paper summarizes existing preclinical
      and clinical evidence on the mechanisms of trastuzumab action and resistance and
      provides an up-to-date overview of novel HER2-directed therapies in clinical
      development.

PMID- 22649739
TI  - Ultrasonographic evaluation of bowel wall thickness and intramural blood flow in
      ulcerative colitis.
AB  - Aim. This study aimed at assessing Doppler ultrasonographic findings of gut wall
      vessels and thickness in active and quiescent ulcerative colitis. Methods. Fifty
      patients with ulcerative colitis were studied using transabdominal grayscale and
      Doppler sonography of sigmoid, distal and middle parts of descending colon in
      different stages of the disease. Thickness of colon wall in the most involved
      site, number of color signals in each box, resistive index (RI), and pulsatility
      index (PI) were evaluated. Results. The median thickness of the colon wall in the
      most involved sites was 4.3 mm in acute phase and 4.4 mm in the inactive phase (P
      = 0.47). The median number of the color signals in the active phase at the most
      involved site, distal part of descending colon and sigmoid was higher than that
      of the color signals in the inactive phase (P = 0.0001). In the most involved
      site, the PI and RI were undetectable in the inactive phase. The median PI was
      1.4 in the mild phase, 1.3 in the moderate phase, and 1.1 in the severe phase (P
      = 0.002). Conclusion. In contrast to the colon wall thickness, increased
      intramural blood flow reflected the clinical severity in ulcerative colitis
      patients.

PMID- 22649740
TI  - Outcomes of open subacromial decompression after failed arthroscopic
      acromioplasty.
AB  - Aim. To prospectively assess the effectiveness of revision with open subacromial
      decompression in patients who had a previous unsatisfactory outcome with the
      arthroscopic procedure. Methods. 11 patients were identified for the study, who
      did not demonstrate expected improvement in symptoms after arthroscopic
      acromioplasty. All patients underwent structured rehabilitation. Functional
      evaluation was conducted using the Hospital for Special Surgery, New York,
      shoulder rating questionnaire. Results. M : F was 7 : 4. The mean age was 57
      years. The average shoulder score improved from 49.6 preoperatively to 56
      postoperatively at an average followup of 16 months. Two patients showed
      deterioration in their shoulder scores after revision while the rest showed only
      marginal improvement. All except one patient stated that they would opt for
      surgery again if given a second chance. Conclusion. In the group of patients that
      fail to benefit from the arthroscopic decompression, only a marginal improvement
      was noted after revision with open decompression.

PMID- 22649741
TI  - Low-dose chemotherapy with insulin (insulin potentiation therapy) in combination
      with hormone therapy for treatment of castration-resistant prostate cancer.
AB  - Purpose. To evaluate the results and quality of life of patients with resistant
      of castration-resistant tumors previously treated with Insulin-potentiation
      therapy (IPT) combined with hormone therapy. Materials and methods. Sixteen
      patients with metastasis prostate tumors after bilateral castration, androgenic
      blockade, and progression of the disease were observed during the study. The
      patients were divided into two groups: group A consisting of 8 patients treated
      with low-dose chemotherapy Epirubicin, Vinblastine, and Cyclophosphamide combined
      with LHRH agonist and group B consisting of another 8 patients treated with low
      dose chemotherapy Docetaxel combined with LHRH agonist. Results. The overall
      (groups A and B) results concerning PSA after the sixth IPT show partial effect
      in 8 out of 16 (50%) patients, stabilization in 4 out of 16 (25%), and
      progression in 4 out of 16 (25%). The median survival for all treated patients is
      11,7 months (range 3-30 months). During the treatment no significant side effects
      were observed, and no lethal cases occurred. Conclusion. In spite of the small
      number of the treated patients with castration-resistant prostate tumors, the
      preliminary results are promising and this gives us hope and expectations for
      future serious multicenter research over the possibilities for routine
      implementation of IPTLD.

PMID- 22649742
TI  - Ultrasound-guided popliteal nerve block in a patient with malignant degeneration
      of neurofibromatosis 1.
AB  - A 41-year-old female patient with neurofibromatosis 1 presented with new
      neurologic deficits secondary to malignant degeneration of a tibial lesion.
      Ultrasound mapping of the popliteal nerve revealed changes consistent with an
      intraneural neurofibroma. Successful popliteal nerve blockade was achieved under
      ultrasound guidance.

PMID- 22649743
TI  - Acute eosinophilic ascites in a middle-aged man.
AB  - Eosinophilic gastroenteritis is a rare condition characterized by recurrent
      eosinophilic infiltration of portions of the GI tract and presenting with
      nonspecific GI symptoms in association with peripheral eosinophilia. Its etiology
      and pathogenesis remain unclear and its symptoms overlap with many GI and
      systemic diseases. Thus, both gastroenterologists and general internists need to
      be aware of this rare condition. We present a case of a 55-year-old male with
      diffuse abdominal pain and distention for two weeks. His physical examination was
      significant for moderate ascites. Initial work-up demonstrated severe peripheral
      blood eosinophilia, normal liver function tests, thickening of the stomach and
      small bowel wall, and elevated serum IgE. Upper endoscopy and extensive testing
      for malignancy and parasitic infections failed to establish a diagnosis. Ascitic
      fluid analysis showed significant eosinophilia. Further, a full-thickness jejunal
      showed marked eosinophilic infiltration of the serosa and muscularis propria.
      Subsequent treatment with oral prednisone resulted in normalization of laboratory
      and radiologic abnormalities in a few week period.

PMID- 22649744
TI  - Bilateral progressive idiopathic annular lipid keratopathy.
AB  - Purpose. To report two unusual cases of idiopathic lipid keratopathy with
      symmetrical bilateral annular corneal lipid infiltration and describe confocal
      microscopy findings. Methods. Case reports. Results. We report two patients with
      bilateral peripheral deep stromal lipid deposits beginning in an arcuate pattern
      and progressing to a complete annular shape. Cholesterol crystals were observed
      in the paracentral area in both cases with characteristic crystalline-like
      structures in the confocal microscopy. Deep thin corneal blood vessels were
      observed in one patient, but no cause for then was established, despite decades
      of followup. This patient had an idiopathic limbitis as well, occurring in
      episodes. No previous ocular trauma, systemic disease or family history was
      reported for both cases. Conclusion. These two cases of idiopathic annular lipid
      keratopathy were observed for more than a decade with documented slow and
      insidious progression of the infiltrates, in spite of the use of topical steroids
      in one case. In the majority of other reported cases, a penetrating keratoplasty
      was made necessary. Differently, we showed that the visual acuity can remain
      quite good for years with very slow deterioration.

PMID- 22649745
TI  - An acute case of herpes zoster ophthalmicus with ophthalmoplegia.
AB  - Herpes zoster ophthalmicus (HZO) with oculomotor nerve involvement is rare, even
      rarer as an acute presentation rather than sequelae of HZO. In this paper we
      present a case of cutaneous HZO in which our patient's initial presentation was
      one of complete ophthalmoplegia.

PMID- 22649746
TI  - Bifocal Spinal Cord Injury without Radiographic Abnormalities in a 5-Year Old
      Boy: A Case Report.
AB  - We present the extremely unusual case of a 5-year-old boy with a bifocal
      (cervical as well as lumbar) spinal cord injury without radiographic
      abnormalities (SCIWORAs). The MRI showed cord oedema at the level of C2 and T10.
      We propose that during the motor vehicle crash severe propulsion of the head with
      a flexed lumbar region resulted in a traction injury to the lower thoracic and
      lumbar spine and maximum flexion caused SCIWORA in C2.

PMID- 22649747
TI  - Successful management of a recurrent supralevator abscess: a case report.
AB  - Anorectal abscesses are commonly encountered in clinical surgical practice. These
      abscesses require surgical management. Supralevator abscesses are thought to
      originate either from an ischiorectal or intersphincteric abscess extension or
      from an intraperitoneal source. These abscesses are quite uncommon and present a
      difficult surgical problem. We present a case here of a 42-year-old female with a
      recurrent supralevator abscess requiring multiple surgical procedures for
      adequate drainage and care of her abscess.

PMID- 22649748
TI  - Mechanisms of speciation.

PMID- 22649749
TI  - Acylation of Chiral Alcohols: A Simple Procedure for Chiral GC Analysis.
AB  - The use of iodine as a catalyst and either acetic or trifluoroacetic acid as a
      derivatizing reagent for determining the enantiomeric composition of acyclic and
      cyclic aliphatic chiral alcohols was investigated. Optimal conditions were
      selected according to the molar ratio of alcohol to acid, the reaction time, and
      the reaction temperature. Afterwards, chiral stability of chiral carbons was
      studied. Although no isomerization was observed when acetic acid was used,
      partial isomerization was detected with the trifluoroacetic acid. A series of
      chiral alcohols of a widely varying structural type were then derivatized with
      acetic acid using the optimal conditions. The resolution of the enantiomeric
      esters and the free chiral alcohols was measured using a capillary gas
      chromatograph equipped with a CP Chirasil-DEX CB column. The best resolutions
      were obtained with 2-pentyl acetates (alpha = 3.00) and 2-hexyl acetates (alpha =
      1.95). This method provides a very simple and efficient experimental workup
      procedure for analyzing chiral alcohols by chiral-phase GC.

PMID- 22649750
TI  - Short-wave near-infrared spectrometer for alcohol determination and temperature
      correction.
AB  - A multichannel short-wave near-infrared (SW-NIR) spectrometer module based on
      charge-coupled device (CCD) detection was designed. The design relied on a
      tungsten lamp enhanced by light emitting diodes, a fixed grating monochromator
      and a linear CCD array. The main advantages were high optical resolution and an
      optimized signal-to-noise ratio (0.24 nm and 500, resp.) in the whole wavelength
      range of 650 to 1100 nm. An application to alcohol determination using partial
      least squares calibration and the temperature correction was presented. It was
      found that the direct transfer method had significant systematic prediction
      errors due to temperature effect. Generalized least squares weighting (GLSW)
      method was utilized for temperature correction. After recalibration, the RMSEP
      found for the 25 degrees C model was 0.53% v/v and errors of the same order of
      magnitude were obtained at other temperatures (15, 35 and 40 degrees C). And an
      r(2) better than 0.99 was achieved for each validation set. The possibility and
      accuracy of using the miniature SW-NIR spectrometer and GLSW transfer calibration
      method for alcohol determination at different temperatures were proven. And the
      analysis procedure was simple and fast, allowing a strict control of alcohol
      content in the wine industry.

PMID- 22649751
TI  - Grand challenges in cancer epidemiology and prevention.

PMID- 22649752
TI  - Addressing Cancer Disparities Among American Indians through Innovative
      Technologies and Patient Navigation: The Walking Forward Experience.
AB  - PURPOSE/OBJECTIVE(S): American Indians (AIs) present with more advanced stages of
      cancer and, therefore, suffer from higher cancer mortality rates compared to non
      AIs. Under the National Cancer Institute (NCI) Cancer Disparities Research
      Partnership (CDRP) Program, we have been researching methods of improving cancer
      treatment and outcomes since 2002, for AIs in Western South Dakota, through the
      Walking Forward (WF) Program. MATERIALS/METHODS: This program consists of (a) a
      culturally tailored patient navigation program that facilitated access to
      innovative clinical trials in conjunction with a comprehensive educational
      program encouraging screening and early detection, (b), surveys to evaluate
      barriers to access, (c) clinical trials focusing on reducing treatment length to
      facilitate enhanced participation using brachytherapy and intensity modulated
      radiotherapy (IMRT) for breast and prostate cancer, as AIs live a median of 140
      miles from the cancer center, and (d) a molecular study (ataxia telangiectasia
      mutated) to address whether there is a specific profile that increases toxicity
      risks. RESULTS: We describe the design and implementation of this program,
      summary of previously published results, and ongoing research to influence stage
      at presentation. Some of the critical outcomes include the successful
      implementation of a community-based research program, development of trust within
      tribal communities, identification of barriers, analysis of nearly 400 navigated
      cancer patients, clinical trial accrual rate of 10%, and total enrollment of
      nearly 2,500 AIs on WF research studies. CONCLUSION: This NCI funded pilot
      program has achieved some initial measures of success. A research infrastructure
      has been created in a community setting to address new research questions and
      interventions. Efforts underway to promote cancer education and screening are
      presented, as well as applications of the lessons learned to other health
      disparity populations - both nationally and internationally.

PMID- 22649753
TI  - The implications of breast cancer molecular phenotype for radiation oncology.
AB  - The identification of distinct molecular subtypes of breast cancer has advanced
      the understanding and treatment of breast cancer by providing insight into
      prognosis, patterns of recurrence, and effectiveness of therapy. The prognostic
      significance of molecular phenotype with regard to distant recurrences and
      overall survival are well established in the literature and has been readily
      incorporated into systemic therapy management decisions. However, despite the
      accumulating data suggesting similar prognostic significance for locoregional
      recurrence, integration of molecular phenotype into local management decision
      making has lagged. Although there are some conflicting reports, collectively the
      literature supports a low risk of local recurrence (LR) in the hormone receptor
      (HR) positive luminal subtypes compared to HR negative subtypes [triple negative
      (TN) and HER2-enriched]. The development of targeted therapies, such as
      trastuzumab for the treatment of HER2-enriched subtype, has been shown to
      mitigate the increased risk of LR. Unfortunately, no such remedy exists to
      address the increased risk of LR for patients with TN tumors, making it a
      clinical challenge for radiation oncologists. In this review we discuss the
      correlation between molecular subtype and LR following either breast conservation
      therapy or mastectomy. We also explore the possible mechanisms for increased LR
      in TN breast cancer and radiotherapeutic implications for this population, such
      as the safety of breast conservation, consideration of dose escalation, and the
      appropriateness of accelerated partial breast irradiation.

PMID- 22649754
TI  - Preliminary clinical and pharmacologic investigation of photodynamic therapy with
      the silicon phthalocyanine photosensitizer pc 4 for primary or metastatic
      cutaneous cancers.
AB  - Photodynamic therapy (PDT) for cutaneous malignancies has been found to be an
      effective treatment with a range of photosensitizers. The phthalocyanine Pc 4 was
      developed initially for PDT of primary or metastatic cancers in the skin. A Phase
      I trial was initiated to evaluate the safety and pharmacokinetic profiles of
      systemically administered Pc 4 followed by red light (Pc 4-PDT) in cutaneous
      malignancies. A dose-escalation study of Pc 4 (starting dose 0.135 mg/m(2)) at a
      fixed light fluence (135 J/cm(2) of 675-nm light) was initiated in patients with
      primary or metastatic cutaneous malignancies with the aim of establishing the
      maximum tolerated dose (MTD). Blood samples were taken at intervals over the
      first 60 h post-PDT for pharmacokinetic analysis, and patients were evaluated for
      toxicity and tumor response. A total of three patients (two females with breast
      cancer and one male with cutaneous T-cell lymphoma) were enrolled and treated
      over the dose range of 0.135 mg/m(2) (first dose level) to 0.54 mg/m(2) (third
      dose level). Grade 3 erythema within the photoirradiated area was induced in
      patient 2, and transient tumor regression in patient 3, in spite of the low
      photosensitizer doses. Pharmacokinetic observations fit a three-compartment
      exponential elimination model with an initial rapid distribution phase (~0.2 h)
      and relatively long terminal elimination phase (~28 h), Because of restrictive
      exclusion criteria and resultant poor accrual, the trial was closed before MTD
      could be reached. While the limited accrual to this initial Phase I study did not
      establish the MTD nor establish a complete pharmacokinetic and safety profile of
      intravenous Pc 4-PDT, these preliminary data support further Phase I testing of
      this new photosensitizer.

PMID- 22649755
TI  - Grand challenges for cancer imaging and diagnosis.

PMID- 22649756
TI  - Guggulsterone-mediated enhancement of radiosensitivity in human tumor cell lines.
AB  - PURPOSE: To observe the effect of guggulsterone (GS) on the radiation response in
      human cancer cell lines. MATERIALS AND METHODS: The radiation response of cancer
      cells treated with GS was observed by cell survival studies, cell growth assay,
      NF-kappaB activity assay, western blotting of some key growth promoting
      receptors, the DNA repair protein gammaH2AX, and flow cytometry for DNA analyses.
      RESULTS: GS inhibited radiation induced NF-kappaB activation and enhanced
      radiosensitivity in the pancreatic cell line, PC-Sw. It reduced both cell cycle
      movement and cell growth. GS reduced ERalpha protein in MCF7 cells and IGF1-Rbeta
      protein in colon cancer cells and pancreatic cancer cells and inhibited DNA
      double strand break (DSB) repair following radiation. CONCLUSION: GS induced
      radiation sensitization may be due to several different mechanisms including the
      inhibition of NF-kappaB activation and reductions in IGF1-Rbeta. In addition, GS
      induced gammaH2AX formation, primarily in the S-phase, indicates that DNA DSB's
      in the S-phase may be another reason for GS induced radiosensitivity. ERalpha
      down-regulation in response to GS suggests that it can be of potential use in the
      treatment of estrogen positive tumors that are resistant to tamoxifen.

PMID- 22649758
TI  - Grand challenges in oncology.

PMID- 22649757
TI  - Integration of Principles of Systems Biology and Radiation Biology: Toward
      Development of in silico Models to Optimize IUdR-Mediated Radiosensitization of
      DNA Mismatch Repair Deficient (Damage Tolerant) Human Cancers.
AB  - Over the last 7 years, we have focused our experimental and computational
      research efforts on improving our understanding of the biochemical, molecular,
      and cellular processing of iododeoxyuridine (IUdR) and ionizing radiation (IR)
      induced DNA base damage by DNA mismatch repair (MMR). These coordinated research
      efforts, sponsored by the National Cancer Institute Integrative Cancer Biology
      Program (ICBP), brought together system scientists with expertise in engineering,
      mathematics, and complex systems theory and translational cancer researchers with
      expertise in radiation biology. Our overall goal was to begin to develop
      computational models of IUdR- and/or IR-induced base damage processing by MMR
      that may provide new clinical strategies to optimize IUdR-mediated
      radiosensitization in MMR deficient (MMR(-)) "damage tolerant" human cancers.
      Using multiple scales of experimental testing, ranging from purified protein
      systems to in vitro (cellular) and to in vivo (human tumor xenografts in athymic
      mice) models, we have begun to integrate and interpolate these experimental data
      with hybrid stochastic biochemical models of MMR damage processing and
      probabilistic cell cycle regulation models through a systems biology approach. In
      this article, we highlight the results and current status of our integration of
      radiation biology approaches and computational modeling to enhance IUdR-mediated
      radiosensitization in MMR(-) damage tolerant cancers.

PMID- 22649759
TI  - Non-small cell lung cancer: the challenges of the next decade.

PMID- 22649760
TI  - Genitourinary oncology: current status and future challenges.

PMID- 22649761
TI  - Heterogeneity of focal breast lesions and surrounding tissue assessed by
      mammographic texture analysis: preliminary evidence of an association with tumor
      invasion and estrogen receptor status.
AB  - AIM: This pilot study investigates whether heterogeneity in focal breast lesions
      and surrounding tissue assessed on mammography is potentially related to cancer
      invasion and hormone receptor status. MATERIALS AND METHODS: Texture analysis
      (TA) assessed the heterogeneity of focal lesions and their surrounding tissues in
      digitized mammograms from 11 patients randomly selected from an imaging archive
      [ductal carcinoma in situ (DCIS) only, n = 4; invasive carcinoma (IC) with DCIS,
      n = 3; IC only, n = 4]. TA utilized band-pass image filtration to highlight image
      features at different spatial frequencies (filter values: 1.0-2.5) from fine to
      coarse texture. The distribution of features in the derived images was quantified
      using uniformity. RESULTS: Significant differences in uniformity were observed
      between patient groups for all filter values. With medium scale filtration
      (filter value = 1.5) pure DCIS was more uniform (median = 0.281) than either DCIS
      with IC (median = 0.246, p = 0.0102) or IC (median = 0.249, p = 0.0021). Lesions
      with high levels of estrogen receptor expression were more uniform, most notably
      with coarse filtration (filter values 2.0 and 2.5, r(s) = 0.812, p = 0.002).
      Comparison of uniformity values in focal lesions and surrounding tissue showed
      significant differences between DCIS with or without IC versus IC (p = 0.0009).
      CONCLUSION: This pilot study shows the potential for computer-based assessments
      of heterogeneity within focal mammographic lesions and surrounding tissue to
      identify adverse pathological features in mammographic lesions. The technique
      warrants further investigation as a possible adjunct to existing computer aided
      diagnosis systems.

PMID- 22649763
TI  - Prediction of the lymph node status in patients with intrahepatic
      cholangiocarcinoma: analysis of 320 surgical cases.
AB  - PURPOSE: This study was conducted to identify factors involved in lymph node
      metastasis (LNM) and evaluate their role in predicting LNM in clinically lymph
      node negative (clinical stage I-III) intrahepatic cholangiocarcinoma (ICC).
      MATERIALS AND METHODS: We selected 320 patients who were diagnosed with ICC with
      no apparent clinical LNM (T(1-3)N(0)M(0)). Age, gender, tumor boundary,
      histological differentiation, tumor size, and carbohydrate antigen 19-9 value
      were the studied factors. Univariate and multivariate logistic analysis were
      conducted. Receiver operating characteristics curve analysis was used to test the
      predicting value of each factor and a test which combined the associated factors
      was used to predict LNM. RESULTS: LNM was observed in 76 cases (76/320, 23.8%).
      Univariate and multivariate analysis showed that histological differentiation as
      well as tumor boundary and tumor size significantly correlated with LNM. The
      sensitivity and negative predictive value for LNM for the three factors when
      combined was 96.1 and 95% respectively. This means that 5% of the patients who
      did not have the risk factors mentioned above developed LNM. CONCLUSION: This
      model used the combination of three factors (low-graded histological
      differentiation, distinct tumor boundary, small tumor size) and they proved to be
      useful in predicting LNM in ICC with clinically lymph node negative cases. In
      patients with these criteria, lymph node dissection or lymph node irradiation may
      be omitted and such cases may also be good candidates for stereotactic body
      radiotherapy (SBRT).

PMID- 22649762
TI  - Heat shock proteins as danger signals for cancer detection.
AB  - First discovered in 1962, heat shock proteins (HSPs) are highly studied with
      about 35,500 publications on the subject to date. HSPs are highly conserved,
      function as molecular chaperones for a large panel of "client" proteins and have
      strong cytoprotective properties. Induced by many different stress signals, they
      promote cell survival in adverse conditions. Therefore, their roles have been
      investigated in several conditions and pathologies where HSPs accumulate, such as
      in cancer. Among the diverse mammalian HSPs, some members share several features
      that may qualify them as cancer biomarkers. This review focuses mainly on three
      inducible HSPs: HSP27, HPS70, and HSP90. Our survey of recent literature
      highlights some recurring weaknesses in studies of the HSPs, but also identifies
      findings that indicate that some HSPs have potential as cancer biomarkers for
      successful clinical applications.

PMID- 22649764
TI  - Accelerated Partial Breast Irradiation: Using the CyberKnife as the Radiation
      Delivery Platform in the Treatment of Early Breast Cancer.
AB  - We evaluate the CyberKnife (Accuray Incorporated, Sunnyvale, CA, USA) for non
      invasive delivery of accelerated partial breast irradiation (APBI) in early
      breast cancer patients. Between 6/2009 and 5/2011, nine patients were treated
      with CyberKnife APBI. Normal tissue constraints were imposed as outlined in the
      National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy
      Oncology Group 0413 (NSABP/RTOG) Protocol (Vicini and White, 2007). Patients
      received a total dose of 30 Gy in five fractions (group 1, n = 2) or 34 Gy in 10
      fractions (group 2, n = 7) delivered to the planning treatment volume (PTV)
      defined as the clinical target volume (CTV) +2 mm. The CTV was defined as either
      the lumpectomy cavity plus 10 mm (n = 2) or 15 mm (n = 7). The cavity was defined
      by a T2-weighted non-contrast breast MRI fused to a planning non-contrast
      thoracic CT. The CyberKnife Synchrony system tracked gold fiducials sutured into
      the cavity wall during lumpectomy. Treatments started 4-5 weeks after lumpectomy.
      The mean PTV was 100 cm(3) (range, 92-108 cm(3)) and 105 cm(3) (range, 49-241
      cm(3)) and the mean PTV isodose prescription line was 70% for groups 1 and 2,
      respectively. The mean percent of whole breast reference volume receiving 100 and
      50% of the dose (V(100) and V(50)) for group 1 was 11% (range, 8-13%) and 23%
      (range, 16-30%) and for group 2 was 11% (range, 7-14%) and 26% (range, 21-35.0%),
      respectively. At a median 7 months follow-up (range, 4-26 months), no acute
      toxicities were seen. Acute cosmetic outcomes were excellent or good in all
      patients; for those patients with more than 12 months follow-up the late cosmesis
      outcomes were excellent or good. In conclusion, the lack of observable acute side
      effects and current excellent/good cosmetic outcomes is promising. We believe
      this suggests the CyberKnife is a suitable non-invasive radiation platform for
      delivering APBI with achievable normal tissue constraints.

PMID- 22649765
TI  - Evaluation of activity and combination strategies with the microtubule-targeting
      drug sagopilone in breast cancer cell lines.
AB  - Sagopilone, a fully synthetic epothilone, is a microtubule-stabilizing agent
      optimized for high in vitro and in vivo activity against a broad range of tumor
      models, including those resistant to paclitaxel and other systemic treatments.
      Sagopilone development is accompanied by translational research studies to
      evaluate the molecular mode of action, to recognize mechanisms leading to
      resistance, to identify predictive response biomarkers, and to establish a
      rationale for combination with different therapies. Here, we profiled sagopilone
      activity in breast cancer cell lines. To analyze the mechanisms of mitotic arrest
      and apoptosis and to identify additional targets and biomarkers, an siRNA-based
      RNAi drug modifier screen interrogating 300 genes was performed in four cancer
      cell lines. Defects of the spindle assembly checkpoint (SAC) were identified to
      cause resistance against sagopilone-induced mitotic arrest and apoptosis.
      Potential biomarkers for resistance could therefore be functional defects like
      polymorphisms or mutations in the SAC, particularly in the central SAC kinase
      BUB1B. Moreover, chromosomal heterogeneity and polyploidy are also potential
      biomarkers of sagopilone resistance since they imply an increased tolerance for
      aberrant mitosis. RNAi screening further demonstrated that the sagopilone-induced
      mitotic arrest can be enhanced by concomitant inhibition of mitotic kinesins,
      thus suggesting a potential combination therapy of sagopilone with a KIF2C (MCAK)
      kinesin inhibitor. However, the combination of sagopilone and inhibition of the
      prophase kinesin KIF11 (EG5) is antagonistic, indicating that the kinesin
      inhibitor has to be highly specific to bring about the required therapeutic
      benefit.

PMID- 22649766
TI  - The Grand Challenges in GI Tract Cancers.

PMID- 22649767
TI  - A SUMOylation Motif in Aurora-A: Implications for Spindle Dynamics and
      Oncogenesis.
AB  - Aurora-A is a serine/threonine kinase that plays critical roles in centrosome
      maturation, spindle dynamics, and chromosome orientation and it is frequently
      over-expressed in human cancers. In this work, we show that Aurora-A interacts
      with the SUMO-conjugating enzyme UBC9 and co-localizes with SUMO1 in mitotic
      cells. Aurora-A can be SUMOylated in vitro and in vivo. Mutation of the highly
      conserved SUMOylation residue lysine 249 significantly disrupts Aurora-A
      SUMOylation and mitotic defects characterized by defective and multipolar
      spindles ensue. The Aurora-A(K249R) mutant has normal kinase activity but
      displays altered dynamics at the mitotic spindle. In addition, ectopic expression
      of the Aurora-A(K249R) mutant results in a significant increase in susceptibility
      to malignant transformation induced by the Ras oncogene. These data suggest that
      modification by SUMO residues may control Aurora-A function at the spindle and
      that deficiency of SUMOylation of this kinase may have important implications for
      tumor development.

PMID- 22649768
TI  - Phase I study of celecoxib with concurrent irinotecan, Cisplatin, and radiation
      therapy for patients with unresectable locally advanced non-small cell lung
      cancer.
AB  - PURPOSE: Preclinical findings suggest that adding targeted therapies to
      combination radiation-chemotherapy can enhance treatment efficacy; however, this
      approach may enhance normal tissue toxicity. We investigated the maximum
      tolerated dose, dose-limiting toxicities, and response rate when the selective
      cyclooxygenase-2 inhibitor celecoxib is added to concurrent irinotecan,
      cisplatin, and radiation therapy for patients with inoperable stage II-III non
      small cell lung cancer (NSCLC). METHODS AND MATERIALS: Eighteen patients were
      analyzed in a phase I clinical dose-escalation trial. Celecoxib was given daily
      beginning 5 days before radiation followed by maintenance doses for 12 weeks.
      Toxicity was graded with the Common Terminology Criteria for Adverse Events V3.0
      and response with the World Health Organization system. Primary endpoints were
      maximum tolerated dose of celecoxib and treatment toxicity; secondary endpoints
      were response and survival rates. RESULTS: The maximum tolerated dose of
      celecoxib was not reached, in part owing to discontinuation of the drug supply.
      At doses of 200 or 400 mg/day, no patients experienced any dose-limiting toxicity
      (acute grade >=4 esophagitis or pneumonitis, neutropenic fever or
      thrombocytopenia requiring transfusion, or acute grade >=3 diarrhea). Grade 3
      toxicities were leukopenia (five patients), fatigue (3), pneumonitis (2), dyspnea
      (1), pain (1), and esophageal stricture (1). Interestingly, pulmonary fibrosis (a
      late toxicity) was no more severe in the higher-dose (400-mg) group and may have
      been less common than in the lower-dose group. The clinical response rate was
      100% (8 complete, 10 partial). Two-year rates were: overall survival 65%; local
      regional control 69%; distant metastasis-free survival 71%; and disease-free
      survival 64%. CONCLUSION: Although preliminary, our results suggest that adding
      celecoxib to concurrent chemoradiation for inoperable NSCLC is safe and can
      improve outcome without increasing normal tissue toxicity.

PMID- 22649769
TI  - Decreased Numbers of CD4(+) Naive and Effector Memory T Cells, and CD8(+) Naive T
      Cells, are Associated with Trichloroethylene Exposure.
AB  - Trichloroethylene (TCE) is a volatile chlorinated organic compound that is
      commonly used as a solvent for lipophilic compounds. Although recognized as an
      animal carcinogen, TCE's carcinogenic potential in humans is still uncertain. We
      have carried out a cross-sectional study of 80 workers exposed to TCE and 96
      unexposed controls matched on age and sex in Guangdong, China to study TCE's
      early biologic effects. We previously reported that the total lymphocyte count
      and each of the major lymphocyte subsets (i.e., CD4(+) T cells, CD8(+) T cells,
      natural killer cells, and B cells) were decreased in TCE-exposed workers compared
      to controls, suggesting a selective effect on lymphoid progenitors, and/or
      lymphocyte survival. To explore which T lymphocyte subsets are affected in the
      same study population, we investigated the effect of TCE exposure on the numbers
      of CD4(+) naive and memory T cells, CD8(+) naive and memory T cells, and
      regulatory T cells by FACS analysis. Linear regression of each subset was used to
      test for differences between exposed workers and controls adjusting for potential
      confounders. We observed that CD4(+) and CD8(+) naive T cell counts were about 8%
      (p = 0.056) and 17% (p = 0.0002) lower, respectively, among exposed workers.
      CD4(+) effector memory T cell counts were decreased by about 20% among TCE
      exposed workers compared to controls (p = 0.001). The selective targeting of TCE
      on CD8(+) naive and possibly CD4(+) naive T cells, and CD4(+) effector memory T
      cells, provide further insights into the immunosuppression-related response of
      human immune cells upon TCE exposure.

PMID- 22649770
TI  - RASSF1A and the rs2073498 Cancer Associated SNP.
AB  - RASSF1A is one of the most frequently inactivated tumor suppressors yet
      identified in human cancer. It is pro-apoptotic and appears to function as a
      scaffolding protein that interacts with a variety of other tumor suppressors to
      modulate their function. It can also complex with the Ras oncoprotein and may
      serve to integrate pro-growth and pro-death signaling pathways. A SNP has been
      identified that is present in approximately 29% of European populations
      [rs2073498, A(133)S]. Several studies have now presented evidence that this SNP
      is associated with an enhanced risk of developing breast cancer. We have used a
      proteomics based approach to identify multiple differences in the pattern of
      protein/protein interactions mediated by the wild type compared to the SNP
      variant protein. We have also identified a significant difference in biological
      activity between wild type and SNP variant protein. However, we have found only a
      very modest association of the SNP with breast cancer predisposition.

PMID- 22649772
TI  - The clone wars - revenge of the metastatic rogue state: the sarcoma paradigm.
AB  - Ewing sarcoma (ES) is the second most common bone tumor affecting primarily
      adolescents and young adults. Despite recent advances in biological
      understanding, intensification of chemotherapeutic treatments, and progress in
      local control with surgery and/or radiation therapy, patients with metastatic or
      recurrent ES continue to have a dismal prognosis with less than 20% overall
      survival. All ES is likely metastatic at diagnosis although our methods of
      detection and classification may not account for this. Progressive disease may
      arise via a combination of: (1) selection of chemotherapy-resistant clones in
      primary tumor, (2) signaling from bone or lung microenvironments that may attract
      tumor cells to distant locations, and/or (3) genetic changes within the ES cells
      themselves due to DNA-damaging chemotherapeutic agents or other "hits." These
      possibilities and the evidence base to support them are explored.

PMID- 22649771
TI  - Coordinate to guard: crosstalk of phosphorylation, sumoylation, and
      ubiquitylation in DNA damage response.
AB  - Small ubiquitin-like modifier-1/2/3 (SUMO-1/2/3) and ubiquitin share similar
      structure and utilize analogous machinery for protein lysine conjugation.
      Although sumoylation and ubiquitylation have distinct functions, they are often
      tightly associated with each other to fine-tune protein fate in transducing
      signals to regulate a wide variety of cellular functions, including DNA damage
      response, cell proliferation, DNA replication, embryonic development, and cell
      differentiation. In this Perspective, we specifically highlight the role of
      sumoylation and ubiquitylation in ataxia-telangiectasia mutated (ATM) signaling
      in response to DNA double-strand breaks and hypothesize that ATM-induced
      phosphorylation is a unique node in regulating SUMO-targeted ubiquitylation in
      mammalian cells to combat DNA damage and to maintain genome integrity. A
      potential role for the coordination of three types of post-translational
      modification in dictating the tempo and extent of cellular response to genotoxic
      stress is speculated.

PMID- 22649773
TI  - Targeting the Immune System to Fight Cancer Using Chemical Receptor Homing
      Vectors Carrying Polyinosine/Cytosine (PolyIC).
AB  - Cancer researchers have been looking for ways to harness the immune system and to
      reinstate immune surveillance, to kill cancer cells without collateral damage.
      Here we scan current approaches to targeting the immune system against cancer,
      and emphasize our own approach. We are using chemical vectors attached to a
      specific ligand, to introduce synthetic dsRNA, polyinosine/cytosine (polyIC),
      into tumors. The ligand binds to a receptor protein that is overexpressed on the
      surface of the tumor cells. Upon ligand binding, the receptor complex is
      internalized, introducing the polyIC into the cell. In this fashion a large
      amount of synthetic dsRNA can be internalized, leading to the activation of dsRNA
      binding proteins, such as dsRNA dependent protein kinase (PKR), Toll-like
      receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-1), and melanoma
      differentiation-associated gene 5 (MDA5). The simultaneous activation of these
      signaling proteins leads to the rapid demise of the targeted cell and to cytokine
      secretion. The cytokines lead to a strong bystander effect and to the recruitment
      of immune cells that converge upon the targeted cells. The bystander effects lead
      to the destruction of neighboring tumor cells not targeted themselves by the
      vector. Normal cells, being more robust than tumor cells, survive. This strategy
      has several advantages: (1) recruitment of the immune system is localized to the
      tumor. (2) The response is rapid, leading to fast tumor eradication. (3) The
      bystander effects lead to the eradication of tumor cells not harboring the
      target. (4) The multiplicity of pro-death signaling pathways elicited by PolyIC
      minimizes the likelihood of the emergence of resistance. In this chapter we focus
      on EGFR as the targeted receptor, which is overexpressed in many tumors. In
      principle, the strategy can be extended to other tumors that overexpress a
      protein that can be internalized by a ligand, which can be a small molecule, a
      single chain antibody, or an affibody.

PMID- 22649775
TI  - Stereotactic body radiation therapy for liver metastases from colorectal cancer:
      analysis of safety, feasibility, and early outcomes.
AB  - INTRODUCTION: Colorectal cancer (CRC) is the third leading cause of cancer
      related death in the U.S. Many patients with CRC develop hepatic metastases as
      the sole site of metastases. Historical treatment options were limited to
      resection or conventional radiation therapy. Stereotactic body radiation therapy
      (SBRT) has emerged as a rational treatment approach. This study reviews our
      experience with SBRT for patients with liver metastases from CRC. MATERIALS AND
      METHODS: Fourteen histologically confirmed hepatic CRC metastases in 11
      consecutive patients were identified between November, 2004 and June, 2009 at
      Georgetown University. All patients underwent CT-based treatment planning; a few
      also had MRI or PET/CT. All patients had fiducial markers placed under CT
      guidance and were treated using the CyberKnife system. Treatment response and
      toxicities were examined; survival and local control were evaluated. RESULTS:
      Most patients were treated to a single hepatic lesion (n = 8), with a few treated
      to two lesions (n = 3). Median treatment volume was 99.7 cm(3), and lesions were
      treated to a median BED(10) of 49.7 Gy (range: 28-100.8 Gy). Median follow-up was
      21 months; median survival was 16.1 months, with 2 year actuarial survival of
      25.7%. One year local control was 72%. Among patients with post-treatment
      imaging, eight had stable disease (80%) and two had progressive disease (20%) at
      first follow-up. The most common grade 1-2 acute toxicities included nausea and
      alterations in liver function tests; there was one grade 3 toxicity (elevated
      bilirubin), and no grade 4-5 toxicities. DISCUSSION: SBRT is safe and feasible
      for the treatment of limited hepatic metastases from CRC. Our results compare
      favorably with outcomes from previous studies of SBRT. Further studies are needed
      to better define patient eligibility, study the role of combined modality
      treatment, optimize treatment parameters, and characterize quality of life after
      treatment.

PMID- 22649774
TI  - K63-linked ubiquitination in kinase activation and cancer.
AB  - Ubiquitination has been demonstrated to play a pivotal role in multiple
      biological functions, which include cell growth, proliferation, apoptosis, DNA
      damage response, innate immune response, and neuronal degeneration. Although the
      role of ubiquitination in targeting proteins for proteasome-dependent degradation
      have been extensively studied and well-characterized, the critical non
      proteolytic functions of ubiquitination, such as protein trafficking and kinase
      activation, involved in cell survival and cancer development, just start to
      emerge, In this review, we will summarize recent progresses in elucidating the
      non-proteolytic function of ubiquitination signaling in protein kinase activation
      and its implications in human cancers. The advancement in the understanding of
      the novel functions of ubiquitination in signal transduction pathways downstream
      of growth factor receptors may provide novel paradigms for the treatment of human
      cancers.

PMID- 22649777
TI  - Regulation of ubiquitination-mediated protein degradation by survival kinases in
      cancer.
AB  - The ubiquitin-proteasome system is essential for multiple physiological processes
      via selective degradation of target proteins and has been shown to plays a
      critical role in human cancer. Activation of oncogenic factors and inhibition of
      tumor suppressors have been shown to be essential for cancer development, and
      protein ubiquitination has been linked to the regulation of oncogenic factors and
      tumor suppressors. Three kinases, AKT, extracellular signal-regulated kinase, and
      IkappaB kinase, we refer to as oncokinases, are activated in multiple human
      cancers. We and others have identified several key downstream targets that are
      commonly regulated by these oncokinases, some of which are regulated directly or
      indirectly via ubiquitin-mediated proteasome degradation, including FOXO3, beta
      catenin, myeloid cell leukemia-1, and Snail. In this review, we summarize these
      findings from our and other groups and discuss potential future studies and
      applications in the clinic.

PMID- 22649778
TI  - Glycogen Synthesis is Induced in Hypoxia by the Hypoxia-Inducible Factor and
      Promotes Cancer Cell Survival.
AB  - The hypoxia-inducible factor 1 (HIF-1), in addition to genetic and epigenetic
      changes, is largely responsible for alterations in cell metabolism in hypoxic
      tumor cells. This transcription factor not only favors cell proliferation through
      the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid
      production but also stimulates nutrient supply by mediating adaptive survival
      mechanisms. In this study we showed that glycogen synthesis is enhanced in non
      cancer and cancer cells when exposed to hypoxia, resulting in a large increase in
      glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of
      the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1), were increased in
      hypoxia. We showed that induction of glycogen storage as well as PGM1 expression
      were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen
      stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis
      allows these "hypoxia-preconditioned" cells to confront and survive glucose
      deprivation. In contrast normoxic control cells exhibit a high rate of cell death
      following glucose removal. These findings point to the important role of hypoxia
      and HIF in inducing mechanisms of rapid adaptation and survival in response to a
      decrease in oxygen tension. We propose that a decrease in pO(2) acts as an
      "alarm" that prepares the cells to face subsequent nutrient depletion and to
      survive.

PMID- 22649776
TI  - The Role of Elongin BC-Containing Ubiquitin Ligases.
AB  - The Elongin complex was originally identified as a positive regulator of RNA
      polymerase II and is composed of a transcriptionally active subunit (A) and two
      regulatory subunits (B and C). The Elongin BC complex enhances the
      transcriptional activity of Elongin A. "Classical" SOCS box-containing proteins
      interact with the Elongin BC complex and have ubiquitin ligase activity. They
      also interact with the scaffold protein Cullin (Cul) and the RING domain protein
      Rbx and thereby are members of the Cullin RING ligase (CRL) superfamily. The
      Elongin BC complex acts as an adaptor connecting Cul and SOCS box proteins.
      Recently, it was demonstrated that classical SOCS box proteins can be further
      divided into two groups, Cul2- and Cul5-type proteins. The classical SOCS box
      containing protein pVHL is now classified as a Cul2-type protein. The Elongin BC
      complex containing CRL family is now considered two distinct protein assemblies,
      which play an important role in regulating a variety of cellular processes such
      as tumorigenesis, signal transduction, cell motility, and differentiation.

PMID- 22649779
TI  - Family history of cancer in benign brain tumor subtypes versus gliomas.
AB  - PURPOSE: Family history is associated with gliomas, but this association has not
      been established for benign brain tumors. Using information from newly diagnosed
      primary brain tumor patients, we describe patterns of family cancer histories in
      patients with benign brain tumors and compare those to patients with gliomas.
      METHODS: Newly diagnosed primary brain tumor patients were identified as part of
      the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone
      interview about personal medical history, family history of cancer, and other
      exposures. Information was available from 33 acoustic neuroma (65%), 78
      meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%).
      The association between family history of cancer and each subtype was compared
      with gliomas using unconditional logistic regression models generating odds
      ratios (ORs) and 95% confidence intervals. RESULTS: There was no significant
      difference in family history of cancer between patients with glioma and benign
      subtypes. CONCLUSION: The results suggest that benign brain tumor may have an
      association with family history of cancer. More studies are warranted to
      disentangle the potential genetic and/or environmental causes for these diseases.

PMID- 22649780
TI  - Pathogenic Role of the CRL4 Ubiquitin Ligase in Human Disease.
AB  - The cullin 4-RING ubiquitin ligase (CRL4) family employs multiple DDB1-CUL4
      associated factors substrate receptors to direct the degradation of proteins
      involved in a wide spectrum of cellular functions. Aberrant expression of the
      cullin 4A (CUL4A) gene is found in many tumor types, while mutations of the
      cullin 4B (CUL4B) gene are causally associated with human X-linked mental
      retardation. This focused review will summarize our current knowledge of the two
      CUL4 family members in the pathogenesis of human malignancy and neuronal disease,
      and discuss their potential as new targets for cancer prevention and therapeutic
      intervention.

PMID- 22649781
TI  - The Natural History of pT1 Colorectal Cancer.
AB  - Colorectal carcinoma invading the submucosa but not the muscular layer (pT1,
      early invasive cancer) represents the earliest form of clinically relevant
      colorectal cancer in most patients. Neoplastic invasion of the submucosa, in
      fact, opens the way to metastasis via the lymphatic and blood vessels, and the
      choice between surveillance and major surgery will turn on its metastatic
      potential. The following histological features predict the risk of metastasis and
      the different clinical outcomes: grade of differentiation of carcinoma,
      lymphovascular invasion, state of the resection margin. Microstaging of invasive
      cancer, namely the width and the depth of submucosal invasion, together with
      tumor budding at the advancing edge allow the metastatic risk to be further
      stratified in minimal, low, and high. Different, although morphologically
      undistinguishable, tumorigenic pathways are supposed to lead to the malignant
      transformation of colonic mucosa and subsequently to drive the progression from
      early to advanced cancer: new biomarkers are needed to identify progressive and
      non-progressive pT1 neoplasia.

PMID- 22649783
TI  - End stage and chronic kidney disease: associations with renal cancer.
AB  - There is a well known association between end stage renal disease and the
      development of kidney cancer in the native kidney of patients requiring renal
      replacement therapy. There is now emerging evidence that lesser degrees of renal
      insufficiency (chronic kidney disease, CKD) are also associated with an increased
      likelihood of cancer in general and kidney cancer in particular.
      Nephropathological changes are commonly observed in the non-tumor bearing
      portions of kidney resected at the time of partial and radical nephrectomy (RN).
      In addition, patients with renal cancer are more likely to have CKD at the time
      of diagnosis and treatment than the general population. The exact mechanism by
      which renal insufficiency transforms normal kidney cells into tumor cells is not
      known. Possible mechanisms include uremic immune inhibition or increased exposure
      to circulating toxins not adequately cleared by the kidneys. Surgeons managing
      kidney tumors must have an increased awareness of their patient's renal
      functional status as they plan their resection. Kidney sparing approaches,
      including partial nephrectomy (PN) or active surveillance in older and morbidly
      ill patients, can prevent CKD or delay the further decline in renal function
      which is well documented with RN. Despite emerging evidence that PN provides
      equivalent local tumor control to RN while at the same time preventing CKD, this
      operation remains under utilized in the United States and abroad. Increased
      awareness of the bi directional relationship between kidney function and kidney
      cancer is essential in the contemporary management of kidney cancer.

PMID- 22649782
TI  - Histone ubiquitination and deubiquitination in transcription, DNA damage
      response, and cancer.
AB  - Histone post-transcriptional modifications play essential roles in regulation of
      all DNA related processes. Among them, histone ubiquitination has been discovered
      for more than three decades. However, its functions are still less well
      understood than other histone modifications such as methylation and acetylation.
      In this review, we will summarize our current understanding of histone
      ubiquitination and deubiquitination. In particular, we will focus on how they are
      regulated by histone ubiquitin ligases and deubiquitinating enzymes. We will then
      discuss the roles of histone ubiquitination in transcription and DNA damage
      response and the crosstalk between histone ubiquitination and other histone
      modifications. Finally, we will review the important roles of histone
      ubiquitination in stem cell biology and cancer.

PMID- 22649785
TI  - The Roles of VHL-Dependent Ubiquitination in Signaling and Cancer.
AB  - The function of tumor suppressor VHL is compromised in the vast majority of clear
      cell renal cell carcinoma, and its mutations or loss of expression was causal for
      this disease. pVHL was found to be a substrate recognition subunit of an E3
      ubiquitin ligase, and most of the tumor-derived mutations disrupt this function.
      pVHL was found to bind to the alpha subunits of hypoxia-inducible factor (HIF)
      and promote their ubiquitination and proteasomal degradation. Proline
      hydroxylation on key sites of HIFalpha provides the binding signal for pVHL E3
      ligase complex. Beside HIFalpha, several other VHL targets have been identified,
      including activated epidermal growth factor receptor (EGFR), RNA polymerase II
      subunits RPB1 and hsRPB7, atypical protein kinase C (PKC), Sprouty2, beta
      adrenergic receptor II, and Myb-binding protein p160. HIFalpha is the most well
      studied substrate and has been proven to be critical for pVHL's tumor suppressor
      function, but the activated EGFR and PKC and other pVHL substrates might also be
      important for tumor growth and drug response. Their regulations by pVHL and their
      relevance to signaling and cancer are discussed.

PMID- 22649784
TI  - Role of STAT3 in Transformation and Drug Resistance in CML.
AB  - Chronic myeloid leukemia (CML) is initially driven by the bcr-abl fusion
      oncoprotein. The identification of bcr-abl led to the discovery and rapid
      translation into the clinic of bcr-abl kinase inhibitors. Although, bcr-abl
      inhibitors are efficacious, experimental evidence indicates that targeting bcr
      abl is not sufficient for elimination of minimal residual disease found within
      the bone marrow (BM). Experimental evidence indicates that the failure to
      eliminate the leukemic stem cell contributes to persistent minimal residual
      disease. Thus curative strategies will likely need to focus on strategies where
      bcr-abl inhibitors are given in combination with agents that specifically target
      the leukemic stem cell or the leukemic stem cell niche. One potential target to
      be exploited is the Janus kinase (JAK)/signal transducers and activators of
      transcription 3 (STAT3) pathway. Recently using STAT3 conditional knock-out mice
      it was shown that STAT3 is critical for initiating the disease. Interestingly, in
      the absence of treatment, STAT3 was not shown to be required for maintenance of
      the disease, suggesting that STAT3 is required only in the tumor initiating stem
      cell population (Hoelbl et al., 2010). In the context of the BM microenvironment,
      STAT3 is activated in a bcr-abl independent manner by the cytokine milieu.
      Activation of JAK/STAT3 was shown to contribute to cell survival even in the
      event of complete inhibition of bcr-abl activity within the BM compartment. Taken
      together, these studies suggest that JAK/STAT3 is an attractive therapeutic
      target for developing strategies for targeting the JAK-STAT3 pathway in
      combination with bcr-abl kinase inhibitors and may represent a viable strategy
      for eliminating or reducing minimal residual disease located in the BM in CML.

PMID- 22649786
TI  - The genomic and proteomic content of cancer cell-derived exosomes.
AB  - Exosomes are secreted membrane vesicles that have been proposed as an effective
      means to detect a variety of disease states, including cancer. The properties of
      exosomes, including stability in biological fluids, allow for their efficient
      isolation and make them an ideal vehicle for studies on early disease detection
      and evaluation. Much data has been collected over recent years regarding the
      messenger RNA, microRNA, and protein contents of exosomes. In addition, many
      studies have described the functional role that exosomes play in disease
      initiation and progression. Tumor cells have been shown to secrete exosomes,
      often in increased amounts compared to normal cells, and these exosomes can carry
      the genomic and proteomic signatures characteristic of the tumor cells from which
      they were derived. While these unique signatures make exosomes ideal for cancer
      detection, exosomes derived from cancer cells have also been shown to play a
      functional role in cancer progression. Here, we review the unique genomic and
      proteomic contents of exosomes originating from cancer cells as well as their
      functional effects to promote tumor progression.

PMID- 22649788
TI  - Comparison of Acute and Late Toxicity of Two Regimens of 3- and 5-Week
      Concomitant Boost Prone IMRT to Standard 6-Week Breast Radiotherapy.
AB  - PURPOSE: Limited information is available comparing toxicity of accelerated
      radiotherapy (RT) to that of standard fractionation RT for early stage breast
      cancer. We report early and late toxicities of two prone regimens of accelerated
      intensity-modulated radiation therapy (IMRT) with a concomitant boost (CB) to the
      tumor bed delivered over 3 or 5 weeks as compared to standard 6 week RT with a
      sequential electron boost. METHODS: From 2/2003 to 12/2007, 169 consecutive
      patients with Stage I-II breast cancer were offered the choice to undergo prone
      RT with either: a 6-week standard RT regimen of 46 Gy/23 fractions (fx) to the
      whole breast (WB), followed by a14 Gy sequential boost (SB) to the tumor bed
      (6wSB), a 5-week regimen of 50 Gy to WB with an IMRT CB of 6.25 Gy in 25 fx
      (5wCB); or a 3-week protocol of 40.5 Gy to WB with an IMRT CB of 7.5 Gy in 15 fx
      (3wCB). These regimens were estimated as biologically equivalent, based on
      alpha/beta = 4 for tumor control. Toxicities were reported using RTOG and
      LENT/SOMA scoring. RESULTS: 51/169 patients chose standard 6wSB, 28 selected
      5wCB, and 90 enrolled in 3wCB protocol. Maximum acute toxicity was Grade 3
      dermatitis in 4% of the patients in the 6wSB compared 1% in 3wCB. In general,
      acute complications (breast pain, fatigue, and dermatitis) were significantly
      less in the 3wCB than in the other schedules (P < 0.05). With a median follow-up
      of 61 months, the only Grade 3 late toxicity was telangiectasia in two patients:
      one in 3wCB and one in 5wCB group. Notably, fibrosis was comparable among the
      three groups (P = NS). CONCLUSION: These preliminary data suggest that
      accelerated regimens of breast RT over 3 or 5 weeks in the prone position, with
      an IMRT tumor bed CB, result in comparable late toxicity to standard
      fractionation with a sequential tumor boost delivered over 6 weeks. As predicted
      by radiobiological modeling the shorter regimen was associated with less acute
      effects.

PMID- 22649787
TI  - ALK Signaling and Target Therapy in Anaplastic Large Cell Lymphoma.
AB  - The discovery by Morris et al. (1994) of the genes contributing to the
      t(2;5)(p23;q35) translocation has laid the foundation for a molecular based
      recognition of anaplastic large cell lymphoma and highlighted the need for a
      further stratification of T-cell neoplasia. Likewise the detection of anaplastic
      lymphoma kinase (ALK) genetic lesions among many human cancers has defined unique
      subsets of cancer patients, providing new opportunities for innovative
      therapeutic interventions. The objective of this review is to appraise the
      molecular mechanisms driving ALK-mediated transformation, and to maintain the
      neoplastic phenotype. The understanding of these events will allow the design and
      implementation of novel tailored strategies for a well-defined subset of cancer
      patients.

PMID- 22649789
TI  - Population based cancer screening programmes as a teachable moment for primary
      prevention interventions. A review of the literature.
AB  - BACKGROUND AND AIM: Unhealthy diet, physical inactivity, and smoking are key risk
      factors for the major non-communicable diseases such as cancer, cardiovascular
      diseases, and diabetes. The screening procedure may represent an ideal setting
      for promoting healthy lifestyles as it represents a time when subjects are
      probably more inclined to consider a relationship between their own habits and
      their effects on health. The aim of this study is to review available evidence
      concerning interventions combining screening and primary prevention
      interventions, aimed at promoting the adoption of healthy lifestyles. METHODS: We
      searched the MEDLINE and Cochrane library electronic databases for intervention
      studies of primary prevention interventions implemented in the context of
      established screening programmes, or of pilot screening projects, where the study
      design included a comparison group. RESULTS: Comprehensive interventions are
      acceptable for asymptomatic subjects targeted for cancer screening, can result in
      improvements and may be cost-effective. A positive impact of these interventions
      in favoring the adoption of cancer protective dietary behaviors was observed in
      all studies. Conflicting results were instead reported with respect to physical
      activity, while no impact could be observed for interventions aimed to favor
      smoking cessation. CONCLUSIONS: The retrieved studies suggest that the screening
      setting may offer valuable opportunities to provide credible, potentially
      persuasive life style advice, reaching a wide audience. A multiple risk factor
      approach may maximize the benefit of behavioral change, as the same health
      related habits are associated not only with cancers targeted by screening
      interventions, but also with other cancers, coronary artery disease, and other
      chronic conditions, while unhealthy behaviors may be mutually reinforcing. In
      order to cover a maximum number of possibilities, health education programmes
      should include multiple strategies, integrating and combining models of
      individual, social, and environmental change.

PMID- 22649790
TI  - Simultaneous electrochemical measurement of metal and organic propellant
      constituents of gunshot residues.
AB  - The simultaneous electrochemical measurement of heavy-metal and organic
      propellants relevant to gunshot residues (GSRs) is demonstrated. Cyclic
      voltammetry (CV) and cyclic square-wave stripping voltammetry (C-SWV) are shown
      to detect, in a single run, common propellants, such as nitroglycerin (NG) and
      dinitrotoluene (DNT), along with the heavy metal constituents of GSR, antimony
      (Sb), lead (Pb), zinc (Zn) and barium (Ba). The voltammetric detection of the
      stabilizer diphenylamine (DPA) along with inorganic constituents has also been
      examined. The resulting electrochemical signatures combine -in a single
      voltammogram- the response for the various metals and organic species, based on
      the reduction and oxidation peaks of the constituents. Cyclic square-wave
      voltammetry at the glassy carbon electrode (GCE), involving an intermittent
      accumulation at the reversal potentials of -0.95 V (for Sb, Pb, DNT and NG) and 
      1.3 V (for Sb, Pb, Zn and DPA) is particularly useful to offer distinct
      electrochemical signatures for these constituents of GSR mixtures, compared to
      analogous cyclic voltammetric measurements. Simultaneous voltammetric
      measurements of barium (at thin-film Hg GCE) and DNT (at bare GCE) are also
      demonstrated in connection to intermittent accumulation at the reversal potential
      of -2.4 V. Such generation of unique, single-run, information-rich
      inorganic/organic electrochemical fingerprints holds considerable promise for 'on
      the-spot' field identification of individuals firing a weapon, as desired for
      diverse forensic investigations.

PMID- 22649791
TI  - Size-dependence enhancement in electrocatalytic activity of NiHCF-gold
      nanocomposite: potential application in electrochemical sensing.
AB  - A nanocomposite of nickel hexacyanoferrate (NiHCF) was made with gold
      nanoparticles (AuNPs) of two different sizes (20 and 80 nm as AuNP(red) and
      AuNP(blue) respectively), synthesized via 3-glycidoxypropyltrimethoxysilane
      mediated reduction of 3-aminopropyltrimethoxysilane treated gold chloride and
      characterized by scanning electron microscopy and UV-VIS spectroscopy. The size
      of AuNPs was found to influence the two pairs of reversible voltammetric peaks of
      cation rich and cation deficient NiHCF. Such influence was identified from cyclic
      voltammetry of nanocomposite modified electrodes and applications during
      electrochemical sensing of two different analytes hydrazine and glutathione
      (GSH). Electrochemical sensing of hydrazine was based on cyclic voltammetry and
      differential pulse voltammetry (DPV) found as a function of sodium deficient
      NiHCF and was greatly amplified with increasing AuNPs nanogeometry. NiHCF alone
      is not an efficient electrode material for GSH analysis at the level required,
      however, the presence of AuNPs introduces size dependent sensitive and selective
      detection of GSH. GSH sensing based on linear sweep voltammetry (LSV) was found
      to be mediated by the potassium rich form of NiHCF redox couple in the presence
      of AuNPs. The results justified electrochemical detection of these analytes based
      on a mediated mechanism and support the role of AuNPs for facilitated
      electrochemical activity of NiHCF based systems as a function of nanogeometry.

PMID- 22649792
TI  - Synthesis of pi-extended porphyrins via intramolecular oxidative coupling.
AB  - Porphyrins fused with other aromatic units at the meso- and beta-positions have
      recently emerged as a hot topic of research. Their synthesis typically starts
      with preparation of precursors via either Suzuki coupling of a meso
      bromoporphyrin or mixed-aldehyde condensation, and is followed by oxidative
      aromatic coupling, often using high-valent metal reagents (DDQ/Sc(OTf)(3) and
      Fe(III) salts are among the most popular). In recent years, porphyrins were
      oxidatively coupled not only with well-known aromatic hydrocarbons such as
      naphthalene and pyrene, but also with more complex heterocyclic fragments,
      including indole, phenanthro[1,10,9,8-cdefg]carbazole and BODIPY. A subtle
      relationship exists between the output of intramolecular oxidative coupling and
      the nature of the second aromatic moiety, cation in the porphyrin cavity,
      oxidant, and type of remaining meso-substituent. The extension of the porphyrin
      chromophore leads to significant change in linear and non-linear optical
      properties. Very strong bathochromic shifts of absorption (lambda(max) reaching
      1.5-2 microns in some cases) and increases in two-photon absorption cross
      sections are typical for these functional dyes.

PMID- 22649793
TI  - Species boundaries and phylogenetic relationships in the critically endangered
      Asian box turtle genus Cuora.
AB  - Turtles are currently the most endangered major clade of vertebrates on earth,
      and Asian box turtles (Cuora) are in catastrophic decline. Effective management
      of this diverse turtle clade has been hampered by human-mediated, and perhaps
      natural hybridization, resulting in discordance between mitochondrial and nuclear
      markers and confusion regarding species boundaries and phylogenetic relationships
      among hypothesized species of Cuora. Here, we present analyses of mitochondrial
      and nuclear DNA data for all 12 currently hypothesized species to resolve both
      species boundaries and phylogenetic relationships. Our 15-gene, 40-individual
      nuclear data set was frequently in conflict with our mitochondrial data set;
      based on its general concordance with published morphological analyses and the
      strength of 15 independent estimates of evolutionary history, we interpret the
      nuclear data as representing the most reliable estimate of species boundaries and
      phylogeny of Cuora. Our results strongly reiterate the necessity of using
      multiple nuclear markers for phylogeny and species delimitation in these animals,
      including any form of DNA "barcoding", and point to Cuora as an important case
      study where reliance on mitochondrial DNA can lead to incorrect species
      identification.

PMID- 22649794
TI  - Overly excited over preexcitation.

PMID- 22649795
TI  - Inhibition of GSK3 attenuates amphetamine-induced hyperactivity and sensitization
      in the mouse.
AB  - Glycogen synthase kinase 3 (GSK3) is implicated in mediating dopamine-dependent
      behaviors. Previous studies have demonstrated the ability of amphetamine, which
      increases extracellular dopamine levels and influences behavior, to regulate the
      activity of GSK3. This study used valproic acid and the selective GSK3 inhibitor,
      SB 216763, to examine the role of GSK3 in amphetamine-induced hyperactivity and
      the development of sensitized stereotypic behavior. Pretreatment with valproic
      acid (50-300 mg/kg, i.p.) or SB 216763 (2.5-5 mg/kg, i.p.) prior to amphetamine
      (2 mg/kg, i.p.) significantly reduced amphetamineinduced ambulation and
      stereotypy. To assess the development of sensitization to the stereotypic effects
      of amphetamine, mice were pretreated daily with valproic acid (300 mg/kg) or SB
      216763 (5 mg/kg) prior to amphetamine (2 mg/kg) for 5 days. Upon amphetamine
      challenge (1 mg/kg) 7 days later, mice pretreated with valproate or SB 216763
      showed a significant attenuation of amphetamine-induced sensitization of
      stereotypy. To determine whether regulation of GSK3 activity was associated with
      attenuation of acute amphetamine-induced hyperactivity by valproic acid,
      valproate (300 mg/kg) or vehicle was injected prior to amphetamine (2 mg/kg) or
      saline and brain tissue obtained. Analysis of the levels of phospho-GSK3alpha and
      beta by immunoblot indicated that valproate increased phosphorylation of ser21
      GSK3alpha in the frontal cortex, as well as ser9-GSK3beta in the frontal cortex
      and caudate putamen of amphetamine-injected mice. These data support a role for
      GSK3 in acute amphetamine-induced hyperactivity and the development of
      sensitization to amphetamine-induced stereotypy.

PMID- 22649796
TI  - Reactivation kinetics of a series of related bispyridinium oximes with
      organophosphate-inhibited human acetylcholinesterase--Structure-activity
      relationships.
AB  - Despite extensive research in the last six decades, oximes are the only available
      drugs which enable a causal treatment of poisoning by organophosphorus compounds
      (OP). However, numerous in vitro and in vivo studies demonstrated a limited
      ability of these oximes to reactivate acetylcholinesterase (AChE) inhibited by
      different OP pesticides and nerve agents. New oximes were mostly tested for their
      therapeutic efficacy by using different animal models and for their reactivating
      potency with AChE from different species. Due to the use of different
      experimental protocols a comparison of data from the various studies is hardly
      possible. Now, we found it tempting to determine the reactivation kinetics of a
      series of bispyridinium oximes bearing one or two oxime groups at different
      positions and having an oxybismethylene or a trimethylene linker under identical
      conditions with human AChE inhibited by structurally different OP. The data
      indicate that the position of the oxime group(s) is decisive for the reactivating
      potency and that different positions of the oxime groups are important for
      different OP inhibitors while the nature of the linker, oxybismethylene or
      trimethylene, is obviously of minor importance. Hence, these and previous data
      emphasize the necessity for thorough kinetic investigations of OP-oxime-AChE
      interactions and underline the difficulty to develop a broad spectrum oxime
      reactivator which is efficient against structurally different OP inhibitors.

PMID- 22649797
TI  - Impact of tryptophan hydroxylase 2 G-703T polymorphism on anger-related
      personality traits and orbitofrontal cortex.
AB  - Genetic variation in human tryptophan hydroxylase 2 (TPH2) influences TPH
      enzymatic activity and is associated with emotion-related traits and mood
      disorders. The present study investigated the effect of the TPH2 G-703T
      polymorphism on regional brain volume, assessed using voxel-based morphometry
      (VBM), and anger traits in mentally healthy individuals. We examined 63 healthy
      subjects to investigate structural abnormalities using a 1.5-T magnetic resonance
      imaging system, which was normalized to a customized T1 template and segmented
      with VBM. The VBM data were analyzed using an analysis of covariance, with age as
      a covariate. All subjects were assessed with the state-trait anger expression
      inventory (STAXI) and genotyped for TPH2 G-703T. The subjects with G/G genotype
      had significantly higher anger control (AX-Con) anger scores than T allele
      carriers (G/T and T/T genotype). There was a negative correlation between the
      anger out (AX-Out) and trait anger (T-Ang) scores and gray matter concentration
      (GMC) in the inferior orbitofrontal cortex (OFC) and hippocampus. Compared to T
      allele carriers, subjects with the G/G genotype had significantly lower GMC in
      the inferior OFC. Our findings suggest that OFC is an intermediate phenotype that
      bridges serotonin synthesis and anger-related traits. The mechanism underlying
      the effect of the TPH2 gene on OFC abnormality, however, may be complex and may
      involve several processes related to anger expression.

PMID- 22649798
TI  - Retraction. Enhanced flagging and improved clinical sensitivity on the new DxH
      300TM Coulter(r) cellular analysis system.

PMID- 22649807
TI  - Peripheral artery disease.  This increasingly common disorder often goes
      undetected in women until serious problems arise.

PMID- 22649808
TI  - An emergency contraceptive pill helps treat fibroids.

PMID- 22649809
TI  - Spinal manipulation and exercise trump drugs for neck pain.

PMID- 22649810
TI  - Severe sleep apnea is linked to cardiovascular death in women.

PMID- 22649811
TI  - Ask the doctor.  I had pain and some bleeding during bowel movements.  My doctor
      says it's an anal fissure.  What is that, and what's the best way to treat it?

PMID- 22649812
TI  - Ask the doctor.  I recently switched from Prilosec to its generic form
      omeprazole, and it doesn't relieve my heartburn as well as Prilosec.  Aren't
      generics supposed to be the same as the brand-name drugs?

PMID- 22649813
TI  - Adult scoliosis.  Dealing with spinal imbalance.

PMID- 22649814
TI  - Health tips.  Gout and diet choices.

PMID- 22649815
TI  - Rare brain infection avoided with safe sinus irrigation.

PMID- 22649816
TI  - Erectile dysfunction drug approved to treat BPH symptoms.

PMID- 22649817
TI  - Cancer vaccines.  The quest heats up.

PMID- 22649818
TI  - Clostridium difficile. A super serious bug.

PMID- 22649819
TI  - Inside whole grains.  The gritty details.

PMID- 22649820
TI  - I have more eye floaters than in the past.  Should I be worried?

PMID- 22649821
TI  - When my husband drops a piece of food on the floor, he quickly picks it up and
      eats it, claiming that if it's not on the floor for more than five seconds, it's
      just fine.  I think he's asking for trouble.  What do you think?

PMID- 22649823
TI  - 9 ways to improve your smile.  Cosmetic dentistry offers lots of options, but it
      can take a bite out of your budget.

PMID- 22649822
TI  - Latest Alzheimer's research: some rays of hope.

PMID- 22649824
TI  - Tuning in to hearing aids.  Too many Americans are living with untreated hearing
      loss.

PMID- 22649825
TI  - Measuring blood pressure: two arms are better than one.

PMID- 22649826
TI  - Can any medication relieve sleep apnea?

PMID- 22649827
TI  - I am very overweight and considering bariatric surgery, but might liposuction be
      a less drastic option?

PMID- 22649828
TI  - What's the difference between calcium carbonate supplements and calcium citrate
      supplements?

PMID- 22649829
TI  - Screening could prevent more than half of colorectal cancer deaths. Virtual
      colonoscopy is gaining traction due to ease of procedure compared to standard
      colonoscopy.

PMID- 22649830
TI  - 7 risk factors take center stage in preventing cardiovascular death. Physicians
      are asked to adopt a new strategy to improve patients' health and change
      unhealthy behaviors.

PMID- 22649831
TI  - New hepatitis C vaccine announced as infection rate soars. While the news is
      encouraging, the downside is that it could take seven years for the vaccine to
      reach the public.

PMID- 22649833
TI  - Statins may help lower depression risk.  The key could be that the medication
      reduces atherosclerosis in the brain.

PMID- 22649832
TI  - Nuts, beans, seeds: high-impact foods, low-impact co$t. A diet rich in these
      foods confers numerous health benefits--and gives a big bang for your food buck.

PMID- 22649834
TI  - What's the latest thinking on eating beef? Should I totally avoid it or are some
      cuts considered ok to incorporate into my diet?

PMID- 22649835
TI  - I've had terrible heel pain recently, and a friend suggested it might be plantar
      fascitis.  Can you tell me what this is, and what the best treatment might be?

PMID- 22649836
TI  - Can antidepressant medication help relieve arthritis pain?

PMID- 22649837
TI  - My husband has been diagnosed with diastolic dysfunction. Is it life-threatening?

PMID- 22649839
TI  - In praise of reviewers.

PMID- 22649840
TI  - Alert fatigue: implications for the clinical nurse specialist.

PMID- 22649841
TI  - Retooling the Great American Cookie Experiment for nursing grand rounds.

PMID- 22649842
TI  - The worldwide designer drug craze: bath salts behind the counter to get high:
      update for the clinical nurse specialist.

PMID- 22649843
TI  - Pelvic floor muscle training versus no treatment, or inactive control treatments,
      for urinary incontinence in women.

PMID- 22649844
TI  - Evaluating an insulin infusion protocol in an acute care setting.
AB  - OBJECTIVE: The objective of the present study was to evaluate the adherence,
      safety, and effectiveness of a paper versus an electronic insulin infusion
      protocol. DESIGN: This quasi-experimental implementation study compared
      experimental and control groups using a nonrandomized prospective cohort design.
      SETTING: The study was performed at 2 surgical units within a federal tertiary
      care teaching hospital. SAMPLE: Fifty-eight registered nurses volunteered.
      METHODS: We compared time intervals using electronic time stamps from glucometers
      and insulin infusion devices to measure protocol adherence. We assessed perceived
      adherence using a nurse survey, and, to evaluate safety, we reviewed each paper
      protocol infusion calculation for correctness. FINDINGS: Median times from blood
      glucose acquisition to infusion rate adjustment did not differ significantly
      between groups (P = .215). The majority of infusions (96.6%) had glucose
      acquisition times within the acceptable range. Median values of time to next
      "glucose due" did not differ significantly (P = .88), and relative variation in
      median glucose reporting times did not differ significantly between groups (P =
      .16). Evaluation of 877 paper protocol entries demonstrated a 10.7% (n = 94)
      calculation error rate. Registered nurses within the electronic group reported
      greater ease in balancing workload when compared with paper protocol use (P =
      .03). Attitudes did not differ significantly between groups in areas of
      determining infusion adjustment, bolus insulin dose, next glucose due, ease of
      access, understanding protocol, or overall satisfaction. CONCLUSIONS: This study
      demonstrates that one can adhere to an insulin infusion protocol, regardless of
      the format (paper or electronic), in the medical-surgical setting. Our results
      suggest there are safety and nurse workload benefits when an electronic protocol
      was used. IMPLICATIONS: Adherence, safety, and effectiveness can be achieved when
      using insulin infusion in the medical-surgical setting.

PMID- 22649845
TI  - Reporting relationships of clinical nurse specialists in acute care.
AB  - Reporting relationships between clinical nurse specialists (CNSs) and
      administrators (ADMs) can facilitate or constrain CNS practice and affect patient
      outcomes. Limited information is available comparing reporting relationships and
      perspectives of CNSs and ADMs. PURPOSE: The purpose of the present study was to
      describe CNS and ADM reporting relationships and compare their perspectives about
      the activities and outcomes of CNS practice in acute care settings. DESIGN: The
      present study uses a descriptive survey. SETTING: Four healthcare organizations
      in the midwestern United States. SAMPLE: Clinical nurse specialist participants
      (n = 30) were master's degree prepared and employed in an acute care setting.
      Administrator participants (n = 7) were responsible for supervision and
      evaluation of CNSs in their organization. METHODS: Questionnaires were developed
      from literature and content review by experts. The CNS and ADM questionnaires
      contained separate sections for CNS and organization information with parallel
      construction of questions about CNS activities and outcomes. FINDINGS: There was
      variability across organizations related to reporting relationships and structure
      of CNS work. No significant differences were found when comparing CNS and ADM
      perspectives of work activity proportions and the importance of 10 activities and
      7 outcomes. The most important CNS activities included developing clinical
      protocols and guidelines, quality improvement, and coordination of care. The most
      important outcomes included evidence-based nursing care and skilled and competent
      nursing staff. CONCLUSION: Comparing perspectives of work activity time, priority
      activities, and outcomes provides a basis for collaboration between CNSs and ADMs
      in reporting relationships. IMPLICATIONS: Clinical nurse specialists should
      develop positive interactions and shared understanding with ADMs to improve
      effectiveness and enhance patient outcomes.

PMID- 22649846
TI  - Revisioning a clinical nurse specialist curriculum in 3 specialty tracks.
AB  - PURPOSE/OBJECTIVES: The objective of the present study was to revise 3 clinical
      nurse specialist (CNS) educational tracks with current National Association of
      Clinical Nurse Specialist core competencies and educational expectations.
      BACKGROUND AND SIGNIFICANCE: National curricula recommendations include core
      competencies by the 3 spheres of influence. Advanced practice registered nurses
      consensus model educational requirements include a minimum of 500 faculty
      supervised clinical hours; separate graduate courses in pharmacology,
      pathophysiology, and advanced physical assessment; and content in differential
      diagnosis disease management, decision making, and role preparation. DESCRIPTION:
      This educational initiative was designed to (1) align with core competencies and
      advanced practice registered nurse consensus model recommendations, (2) create an
      innovative learning environment, (3) meet the needs of diverse student
      populations, (4) align with emerging doctor of nursing practice programs, (5)
      create a high-efficiency and high-quality environment to manage human and fiscal
      resources, and (6) reduce duplication of efforts. OUTCOME: Courses were revised
      that did not meet current CNS educational preparation expectations. A total of 11
      didactic and clinical sequences courses were developed for the 3 tracks to (1)
      ensure minimum numbers of clinical hours; (2) expand content on health promotion
      and risk reduction, advanced practice nurse role, and the healthcare delivery
      system; (3) consolidate clinical courses; and (4) resequence foundational content
      before beginning clinical courses. INTERPRETATION/CONCLUSION: Revisioning a CNS
      curriculum in 3 specialty tracks is challenging but doable using innovative and
      creative approaches. IMPLICATIONS: The innovative process used to revise our CNS
      curriculum will assist nurse educators faced with similar program delivery
      challenges to meet future directions for educating CNS students in advanced
      nursing practice.

PMID- 22649847
TI  - Teaching clinical nurse specialist students to resolve conflict: strategies that
      promote effective communication and teamwork.

PMID- 22649848
TI  - Profile.

PMID- 22649850
TI  - Modeling the impact of cross-pollination and low toxin expression in corn kernels
      on adaptation of European corn borer (Lepidoptera: Crambidae) to transgenic
      insecticidal corn.
AB  - We used a mathematical model with processes reflecting larval mortality resulting
      from feeding on cross-pollinated ears or Bt ears of corn to analyze the risk of
      evolution of Cry-toxin resistance in Ostrinia nubilalis (Hubner). In the
      simulations, evolution of resistance was delayed equally well by both seed
      mixtures and blocks with the same proportion of refuge. Our results showed that
      Bt-pollen drift has little impact on the evolution of Bt resistance in O.
      nubilalis. However, low-toxin expression in ears of transgenic corn can reduce
      the durability of transgenic corn expressing single toxin, whereas durability of
      pyramided corn hybrids is not significantly reduced. The toxin-survival rate of
      heterozygous larvae in Bt-corn ears expressing one or two proteins has more
      impact on evolution of Bt resistance in O. nubilalis than the parameters related
      to larval movement to Bt ears or the toxin-survival rate of the homozygous
      susceptible larvae in Bt ears. Bt resistance evolves slower when toxin mortality
      is distributed across the first two larval stadia than when only the first
      instars are susceptible to Bt toxins. We suggest that stakeholders examine toxin
      survival rates for insect pests and take into account that instars may feed on
      different parts of Bt corn.

PMID- 22649851
TI  - [Diabetes, associated technologies, and quality of life].

PMID- 22649852
TI  - [Does technology always benefit the patient?].
AB  - In the context of chronic diseases, what contribution is made by technological
      advances which are supposed to benefit the patient? It is important not to get
      bogged down in technicism and to keep the patient as the ultimate purpose. Do the
      patients themselves necessarily see technological advances as being beneficial to
      them? The specific case of a diabetic patient is used as a basis for the
      discussion of this question.

PMID- 22649853
TI  - [A patient education computer program for diabetes].

PMID- 22649854
TI  - [Continuous glucose monitoring, a guide to reading the results and patient
      education].
AB  - Conventional self-monitoring of blood glucose (SMBG) presents a certain number of
      limits. In particular, it cannot provide information on events occurring some
      time before the self-monitoring. Various systems for the continuous monitoring of
      glucose levels have therefore been developed for use in outpatient clinics or at
      home. When being used at home, nursing staff must pay particular attention to the
      therapeutic education of the patient.

PMID- 22649855
TI  - [Understanding continuous glucose monitoring, the diabetologist's point of view].
AB  - Continuous glucose monitoring is a major element of the metabolic assessment of
      the diabetic patient, treated or not by insulin. It forms a complementary
      approach to self-monitoring of blood glucose, without, however, replacing it
      completely. Significant improvements to continuous glucose monitoring tools
      enable them to be used today in outpatient care over prolonged periods.

PMID- 22649856
TI  - [Treatment of diabetic gastroparesis].
AB  - Gastroparesis is a chronic complication of diabetes the appearance of which is
      linked to prolonged exposure to chronic hyperglycaemia. Its physiopathology, its
      clinical expression, its diagnosis (particularly through gastric scintigraphy)
      and its treatment, notably by gastric electrical stimulation are specific.

PMID- 22649857
TI  - [What advances have been made in the treatment of diabetic foot problems?].
AB  - Diabetic foot problems remain, even today, a major world public health issue. The
      identification of patients at risk, diagnosis, prevention, assessment and
      treatments are all aspects of the approach to this pathology.

PMID- 22649858
TI  - [Technological innovation in diabetes: is it suitable for everyone and at what
      price?].
AB  - Tools for monitoring diabetes such as glucose testing devices, continuous glucose
      monitoring and telemedicine in particular, those for treating the disease such as
      insulin pens and pumps, or the "artificial pancreas", are constantly improving
      thanks to technological advances, which also concern preventative treatments.
      However, these new techniques are particularly costly. They also require
      considerable investment from the multidisciplinary nursing team in terms of
      therapeutic patient education.

PMID- 22649860
TI  - Relationship between nursing home safety culture and Joint Commission
      accreditation.
AB  - BACKGROUND: Safety culture interventions in hospitals have been found to be
      associated with improved safety practices and outcomes. Studies in nursing homes
      generally report a poorly developed safety culture. Voluntary accreditation
      provides a structure for organizing care processes and is known to stimulate
      continuous quality improvement and thereby has the potential to stimulate
      improvements in organizational safety culture. The impact of Joint Commission
      accreditation on patient safety culture perceptions among senior managers in
      nursing homes in the United States was assessed. METHODS: A random sample of
      6,000 nursing homes was selected from all 50 states. The Nursing Home Survey on
      Resident Safety Culture was sent to these facilities, and nursing home
      administrators and directors of nursing were instructed to complete the survey.
      Scores were computed using the instrument agreement scale, in which the
      percentage of positive responses represented the summary score. Students' paired
      sample t-tests were used to compare differences in scores between respondents
      from accredited nursing homes and those from nonaccredited nursing homes.
      Multivariate analyses were then used to examine the association between
      accreditation and each resident safety culture (RSC) subscale, controlling for
      facility and market characteristics. RESULTS: The analytic response rate for the
      sample was 67%. After facility and market characteristics were controlled for,
      senior managers in accredited nursing homes rated 8 of the 11 RSC domains
      significantly higher. CONCLUSION: Joint Commission accreditation appeared to be
      associated with a more favorable RSC in nursing homes. Assessing a nursing home's
      RSC is an organization's first step toward improving the culture of safety. These
      findings support the need for further discussion and facilitation of voluntary
      accreditation in nursing homes.

PMID- 22649861
TI  - Electronic health record-based monitoring of primary care patients at risk of
      medication-related toxicity.
AB  - BACKGROUND: Timely laboratory monitoring may reduce the potential harm associated
      with chronic medication use. A study was conducted to determine the proportion of
      patients receiving National Committee for Quality Assurance (NCQA)-recommended
      laboratory medication monitoring in a primary care setting and to assess the
      effect of electronic health record (EHR)-derived, paper-based, provider-specific
      feedback bulletins on subsequent patient receipt of medication monitoring.
      METHODS: In a single-arm, pre-post intervention in two federally qualified
      community health centers in Baltimore, patients targeted were adults prescribed
      at least 6 months (in the preceding year) for at least one index medication
      (digoxin, statins, diuretics, angiotensin-converting enzyme inhibitors/
      angiotensin II-receptor blockers) in a 12-month period (August 2008-July 2009).
      RESULTS: Among the 2,013 patients for whom medication monitoring was recommended,
      42% were overdue for monitoring at some point during the study. As the number of
      index medications the patient was prescribed increased, the likelihood of ever
      being overdue for monitoring decreased. Being listed on the provider-specific
      monitoring bulletin doubled the odds of a patient receiving recommended
      laboratory monitoring before the next measurement period (1-2 months). Limiting
      the intervention to the most overdue patients, however, mitigated its overall
      impact. CONCLUSIONS: Recommended laboratory monitoring of chronic medications
      appears to be inconsistent in primary care, resulting in potential harm for
      individuals at risk for medication-related toxicity. EHRs may be an important
      component of systems designed to improve medication monitoring, but multimodal
      interventions will likely be needed to achieve high reliability.

PMID- 22649859
TI  - Implementing and evaluating a multicomponent inpatient diabetes management
      program: putting research into practice.
AB  - BACKGROUND: Strategies for successful implementation of hospitalwide glucose
      control efforts were addressed in a conceptual model for the development and
      implementation of an institutional inpatient glucose management program.
      CONCEPTUAL MODEL COMPONENTS: The Glucose Steering Committee incrementally
      developed and implemented hospitalwide glucose policies, coupled with targeted
      education and clinical decision support to facilitate policy acceptance and
      uptake by staffwhile incorporating process and outcome measures to objectively
      assess the effectiveness of quality improvement efforts. The model includes four
      components: (1) engaging staff and hospital executives in the importance of
      inpatient glycemic management, (2) educating staff involved in the care of
      patients with diabetes through structured knowledge dissemination, (3) executing
      evidence-based inpatient glucose management through development of policies and
      clinical decision aids, and (4) evaluating intervention effectiveness through
      assessing process measures, intermediary glucometric outcomes, and clinical and
      economic outcomes. An educational curriculum for nursing, provider, and
      pharmacist diabetes education programs and current glucometrics were also
      developed. OUTCOMES: Overall the average patient-day-weighted mean blood glucose
      (PDWMBG) was below the currently recommended maximum of 180 mg/dL in patients
      with diabetes and hyperglycemia, with a significant decrease in PDWMBG of 7.8
      mg/dL in patients with hyperglycemia. The program resulted in an 18.8% reduction
      in hypoglycemia event rates, which was sustained. CONCLUSION: Inpatient glucose
      management remains an important area for patient safety, quality improvement, and
      clinical research, and the implementation model should guide other hospitals in
      their glucose management initiatives.

PMID- 22649862
TI  - Automated dispensing cabinet alert improves compliance with obtaining blood
      cultures before antibiotic administration for patients admitted with pneumonia.
AB  - BACKGROUND: A Centers for Medicare & Medicaid Services (CMS) pneumonia quality
      measures with particular impact on the emergency department (ED) is blood
      cultures prior to antibiotic administration for patients admitted with pneumonia.
      A study was conducted to measure the impact of an automated dispensing cabinet
      (ADC) alert on improving compliance with the quality measure of obtaining blood
      cultures prior to giving antibiotics for patients admitted with pneumonia and who
      have blood cultures ordered. METHODS: The pre-post study involved ED adult
      patient with an admitting diagnosis of pneumonia from October 2007 through
      September 2008. The intervention consisted of a series of questions in the ED
      medication ADC regarding blood culture orders and antibiotic administration.
      Patients with an admitting diagnosis of pneumonia were identified through a
      search of the ED electronic health record (EHR). The proportion of patients in
      whom blood cultures were obtained prior to antibiotic administration in the pre-
      (October 2007-March 2008) and postintervention (April 2008-September 2008)
      periods were compared. The chi-square test was used to test for statistical
      significance. RESULTS: Some 951 patients with pneumonia were identified during
      the study period, 426 pre- and 525 postintervention. Compliance with obtaining
      blood cultures prior to antibiotic administration was 84% (205/245, 95%
      confidence interval [CI]: 79%-88%) and 95% (275/291, 95% CI: 92%-97%) in the pre
      and postintervention periods, respectively (p <. 001). CONCLUSIONS: In this
      population of patients with pneumonia, a series of questions in an ADC improved
      compliance with the quality measure regarding the obtaining of blood cultures
      prior to administering antibiotics to patients in whom blood cultures are
      requested.

PMID- 22649863
TI  - Reporting information on emergency department crowding to the hospital board and
      delivery of time-sensitive care.
AB  - BACKGROUND: Hospital governing boards influence the quality of care that
      hospitals provide by holding senior leaders and managers accountable. A study was
      conducted to determine whether reporting data on emergency department (ED)
      crowding to hospital boards was associated with better performance on a time
      sensitive quality measure for patients with acute myocardial infarction (AMI):
      Primary PCI [percutaneous intervention] Within 90 Minutes of Hospital Arrival.
      METHODS: In a survey, hospital chief quality officers were asked whether the
      following data were reported to the hospital governing board: ED wait times, the
      percentage of ED patients who left without being seen (LWBS), and the percentage
      of admitted ED patients who are boarded in the ED. Responses were paired with
      Centers for Medicare & Medicaid Services (CMS) data on the percentage of eligible
      AMI patients who received PCI within 90 minutes of arrival, which served as the
      hospitals' PCI score. RESULTS: In the sample of 261 hospitals, 133 (51%) of
      hospital governing boards received data on wait times, 125 (48%) received data on
      LWBS, and 63 (24%) received data on ED boarding. After hospital characteristics
      were controlled for, hospitals that reported data on ED boarding to the governing
      board had PCI scores that were 5.5 percentage points higher (that is, better); p
      < .05. There was no association between reporting wait times or LWBS to the board
      and PCI scores. CONCLUSION: Reporting data on the incidence of ED boarding to
      hospital governing boards was associated with better performance for PCI. More
      research is needed to explore the direction of this relationship, but the results
      suggest that hospitals should consider reporting data on ED boarding to their
      boards as a low/no-cost quality improvement activity.

PMID- 22649864
TI  - How to develop a second victim support program: a toolkit for health care
      organizations.
AB  - A toolkit was developed to help health care organizations implement support
      programs for clinicians suffering from the emotional impact of errors and adverse
      events. Based on the best available evidence related to the second victim
      experience, the toolkit consists of 10 modules, each with a series of specific
      action steps, references, and exemplars.

PMID- 22649865
TI  - Decontamination and management of human remains following incidents of hazardous
      chemical release.
AB  - OBJECTIVE: To provide specific guidance and resources for systematic and orderly
      decontamination of human remains resulting from a chemical terrorist attack or
      accidental chemical release. DESIGN: A detailed review and health-based decision
      criteria protocol is summarized. Protocol basis and logic are derived from
      analyses of compound-specific toxicological data and chemical/physical
      characteristics. SETTING: Guidance is suitable for civilian or military settings
      where human remains potentially contaminated with hazardous chemicals may be
      present, such as sites of transportation accidents, terrorist operations, or
      medical examiner processing points. PATIENTS AND PARTICIPANTS: Guidance is
      developed from data-characterizing controlled experiments with laboratory
      animals, fabrics, and materiel. MAIN OUTCOME MEASURE(S): Logic and specific
      procedures for decontamination and management of remains, protection of mortuary
      affairs personnel, and decision criteria to determine when remains are
      sufficiently decontaminated are presented. RESULTS: Established procedures as
      well as existing materiel and available equipment for decontamination and
      verification provide reasonable means to mitigate chemical hazards from
      chemically exposed remains. Unique scenarios such as those involving supralethal
      concentrations of certain liquid chemical warfare agents may prove difficult to
      decontaminate but can be resolved in a timely manner by application of the
      characterized systematic approaches. Decision criteria and protocols to "clear"
      decontaminated remains for transport and processing are also provided.
      CONCLUSIONS: Once appropriate decontamination and verification have been
      accomplished, normal procedures for management of remains and release can be
      followed.

PMID- 22649866
TI  - Optimal emergency personnel allocation after a natural disaster.
AB  - OBJECTIVE: Little work has been devoted to the links between natural disasters,
      subsequent Emergency Medical Services (EMS) network utilization, triage, and
      public awareness. The aim of this study was to investigate the types and
      distribution of emergency calls recorded after each South Florida hurricane
      during the 2005 season, identifying target areas for public health education, and
      emergency personnel use and training. DESIGN: Retrospective database review.
      SETTING: Miami-Dade Fire Rescue (MDFR) emergency dispatch headquarters. PATIENTS,
      PARTICIPANTS: All persons making 911 phone calls to the MDFR emergency dispatch
      headquarters in the 3 days before and after category 3 or higher hurricanes
      during 2005. INTERVENTIONS: None. RESULTS: There were 192,363 emergencies
      reported in 2005. The mean number of 911 emergencies reported per day for the 3
      days before and after Katrina was 503 +/- 26 and 819 +/- 105, respectively (p =
      0.007). The mean number for Wilma was 533 +/- 42 before and 800 +/- 63 after (p =
      0.004). However, Rita had no impact on the number of 911 emergencies reported.
      Katrina resulted in a statistically significant increase in 911 calls for
      breathing (p = 0.03), convulsions and seizures (p = 0.02), and hazardous
      situations (p = 0.04). Rita led to an increase in convulsions and seizures (p =
      0.03). Lastly, Wilma caused a rise in breathing emergencies (p = 0.02) and
      hazardous situations (p = 0.02). CONCLUSIONS: This study suggests that 911 calls
      regarding respiratory complaints, convulsions, seizures, and hazardous situations
      can be expected to significantly increase after a hurricane. Educational
      initiatives, EMS resource allocation, and modified triage systems designed to
      target these areas may limit EMS system-wide strain and improve health outcomes
      following natural disasters.

PMID- 22649867
TI  - The use of volunteer interpreters during the 201 0 Haiti earthquake: lessons
      learned from the USNS COMFORT Operation Unified Response Haiti.
AB  - On January 12, 2010, a 7.0 magnitude Richter earthquake devastated Haiti, leading
      to the world's largest humanitarian effort in 60 years. The catastrophe led to
      massive destruction of homes and buildings, the loss of more than 200,000 lives,
      and overwhelmed the host nation response and its public health infrastructure.
      Among the many responders, the United States Government acted immediately by
      sending assistance to Haiti including a naval hospital ship as a tertiary care
      medical center, the USNS COMFORT. To adequately respond to the acute needs of
      patients, healthcare professionals on the USNS COMFORT relied on Haitian Creole
      speaking volunteers who were recruited by the American Red Cross (ARC). These
      volunteers complemented full-time Creole-speaking military staff on board. The
      ARC provided 78 volunteers who were each able to serve up to 4 weeks on board.
      Volunteers' demographics, such as age and gender, as well as linguistic skills,
      work background, and prior humanitarian assistance experience varied. Volunteer
      efforts were critical in assisting with informed consent for surgery, family
      reunification processes, explanation of diagnosis and treatment, comfort to
      patients and families in various stages of grieving and death, and helping
      healthcare professionals to understand the cultural context and sensitivities
      unique to Haiti. This article explores key lessons learned in the use of
      volunteer interpreters in earthquake disaster relief in Haiti and highlights the
      approaches that optimize volunteer services in such a setting, and which may be
      applicable in similar future events.

PMID- 22649868
TI  - Bioterrorism and disaster preparedness among medical specialties.
AB  - OBJECTIVE: A core priority of all medical specialties includes information for
      members regarding inherent priorities and principles. The authors sought to
      investigate the priority and contribution of various medical specialties to the
      fields of bioterrorism, terrorism, disaster preparedness, and emergency
      preparedness. DESIGN: A mixed study design (quantitative and qualitative) was
      used to identify pertinent characteristics of various medical specialties. A
      scored survey analysis of resources available from the representative
      organizations and/or societies of the primary medical specialties and select
      subspecialties was examined and scored based on availability, ease of
      accessibility, updated status, and content. A MEDLINE search completed through
      PubMed using the medical subject headings bioterrorism, terrorism, disaster
      preparedness, and emergency preparedness coupled with specific medical
      specialties was conducted to assess the involvement and contribution of each to
      the medical literature. MAIN OUTCOME MEASURES: The primary study outcome was to
      evaluate the priority of and existing resources available to members for
      bioterrorism/terrorism and disaster/emergency preparedness among various medical
      specialties as reflected by their representative organizations and scientific
      publication. RESULTS: The search of individual medical specialties and of the
      medical literature (2000-2010) revealed that these topics (via keywords
      bioterrorism, terrorism, disaster preparedness, and emergency preparedness) are
      indeed a priority topic for the majority of medical specialties. A number of
      specialties with expectant priority in these topics were confirmed. All seven
      primary care specialties demonstrated a core priority of these topics and offered
      resources. The MEDLINE (PubMed) search yielded 7,228 articles published from 2000
      to 2010. CONCLUSION: Bioterrorism/terrorism and disaster/ emergency preparedness
      are priority topics of most medical specialties. This core priority is
      demonstrated by both the medical specialty resources in addition to the
      contribution of scientific articles from these medical specialties. This reflects
      the diverse medical care that is necessary for terrorist threats and the
      collaborative efforts that will help to make the medical response to these
      threats more cohesive.

PMID- 22649869
TI  - Global responsibility in mass casualty events: the Israeli experience in Japan.
AB  - OBJECTIVE: To describe humanitarian aid following the 2011 earthquake and tsunami
      in Japan. SETTING: A field hospital deployed in a small Japanese coastal village
      devastated by a major tsunami. PATIENTS: Thousands of Japanese refugees with
      minimal access to medical care. RESULTS: After well-coordinated diplomatic
      efforts, our medical delegation was the first foreign team to deploy in Japan.
      Our facility served as a regional referral center for specialized medical
      treatment. CONCLUSIONS: Following major disasters, even highly modernized
      countries will face an urgent surge in the need of medical resources. These
      situations emphasize the need for global responsibility to provide assistance.

PMID- 22649870
TI  - Prairie North: a joint civilian/military mass casualty exercise highlights the
      role of the National Guard in community disaster response.
AB  - In a joint military/civilian exercise conducted in June 2010, military National
      Guard medical and decontamination response efforts proved to be paramount in
      supporting hospital resources to sustain an adequate response during a simulated
      terrorist event. Traditionally, hospitals include local responders in their
      disaster preparedness but overlook other available state and federal resources
      such as the National Guard. Lessons learned from the exercise included the value
      of regular joint disaster planning and training between the military and civilian
      medical sectors. Additionally, military communication and medical equipment
      compatibility with the civilian infrastructure was identified as one of the top
      areas for the improvement of this joint exercise. Involving the National Guard in
      community disaster planning provides a valuable medical support asset that can be
      critical in responding to multiple casualty events. National Guard response is
      inherently faster than its federal counterpart. Based on the findings from our
      joint exercise, states are encouraged to incorporate their corresponding National
      Guard in civilian critical medical infrastructure disaster preparedness
      activities, as the National Guard can be an integral part of the disaster
      response efforts in real multiple casualty events.

PMID- 22649871
TI  - Medical papyri show the effects of the Santorini eruption heavily influenced the
      development of ancient medicine.
AB  - Exposure to ash from the catastrophic Santorini eruption radically changed Bronze
      Age medicine, triggering the development of new remedies, the wide dissemination
      of medical data, and the transfer of technologies. These developments were
      identified in medical papyri thanks to remedies for ailments linked to volcanic
      matter an oddity in Egypt, a country without volcanoes. The anomaly was traced
      back to the Santorini eruption, which through volcanic ash, acidified bodies of
      waters, and acid rain affected the whole eastern Mediterranean without sparing
      Egypt. Using available technology, doctors developed new remedies for severe
      irritation to eyes from ash and for burns on the skin, or imported foreign
      remedies as exemplified by paragraph 28 of the London Medical Papyrus (L28), thus
      resorting to technology transfer even if so crude. Furthermore, medical manuals
      rather than being guarded by families of physicians were now used to disseminate
      remedies as widely as possible. Finally, besides providing historical data, the
      medical reaction to the Santorini eruption could still be of use today. The
      remedies could be integrated in manuals for emergency situations for population
      left without adequate medical infrastructure at a time of exposure to heavy
      volcanic fallout or acidified rain.

PMID- 22649872
TI  - Postnatal evaluation and outcome of infants with antenatal hydronephrosis.
AB  - This study was aimed at evaluating the clinical outcome of infants with
      antenatally diagnosed hydronephrosis. Our objective was also to determine whether
      there is a significant correlation between anterior posterior pelvic diameter
      (APPD) and urinary tract abnormalities detected. We retrospectively analyzed data
      of 145 infants collected between January 2000 and May 2010. Inclusion criteria
      were the presence of APPD > or = 5 mm on prenatal US scan after 20 weeks of
      gestation, at least 6-month follow-up and at least two postnatal US scans. Most
      patients underwent renal scintigraphy (n = 140, 96.6%) and micturating
      cystourethrography (n = 141, 97.2%). Of 145 infants, 77 (53.1%) had idiopathic or
      transient hydronephrosis. The second most common diagnosis was vesicoureteral
      reflux found in 21 (14.4%) infants, followed by ureteropelvic junction
      obstruction without significant kidney damage found in 18 (12.4%) infants. The
      relative risk of significant urologic abnormality according to the degree of
      antenatal hydronephrosis (ANH) was 21.25 (95% CI: 2.95-156.49) for severe ANH,
      1.57 (95% CI: 0.94-2.62) for moderate ANH and 0.47 (95% CI: 0.33-0.66) for mild
      ANH. There was a significant increase in the riskper increasing degree of
      hydronephrosis. In 19 out of 145 (13.2%) infants, immediate surgery was required.
      These data support the need of antenatal detection and long-term postnatal follow
      up of infants with ANH.

PMID- 22649873
TI  - Participation of children with neurodevelopmental risk factors in the early
      rehabilitation program in relation to the level of parental education.
AB  - Many factors that have an adverse effect on fetal growth and development can
      manifest later in the child's development. Because of the biological basis,
      children born under the influence of these factors belong to the group of
      neurorisk children. They need special attention and prompt participation in the
      early rehabilitation program to encourage the use of brain plasticity. In
      addition to the biological influences, socioeconomic status affects a wide array
      of medical, cognitive and socio-emotional consequences in children, which begin
      before birth and continue into adulthood. This retrospective study included 50
      children aged one to three years, hospitalized at Department of Pediatric
      Rehabilitation, University Department of Rheumatology, Physical Medicine and
      Rehabilitation, Sestre milosrdnice University Hospital Center in Zagreb. The aim
      was to determine the frequency of inclusion of children with neurodevelopmental
      risks in the early rehabilitation program according to the level of parental
      education. The results showed the highest percentage of parents of neurorisk
      children to have high school education, while the smallest number of parents had
      elementary school education. These data pointed to the lack of public awareness
      of the importance of the early period of life. However, they also indicated the
      lack of parental knowledge of their rights and opportunities for involvement of
      their neurorisk children in the early rehabilitation programs.

PMID- 22649874
TI  - Motor and cognitive impairment after stroke.
AB  - Cognitive abilities have great impact on rehabilitation program in stroke
      patients. Therefore, fast and practical psychometric assessment as an indicator
      of individual rehabilitation program is of great importance. The aim of this
      study was to analyze and compare motor and cognitive impairment in stroke
      patients in acute, subacute and chronic phase of the disease, taking age, sex,
      education, stroke risk factors, lateralization and type of stroke in
      consideration. The study included 50 stroke patients, 33 male and 17 female.
      Ischemic stroke was diagnosed in 78% and hemorrhagic stroke in 22% of patients.
      Hypertension was the leading stroke risk factor in 82% of patients. Cognitive
      impairment in acute, subacute and chronic phase of the disease was noticed in 12%
      of stroke patients with ischemia in the left brain hemisphere, mMMSE average
      score 31 and SKT score 19, IQ under 90. Better motor recovery in acute and
      subacute phase of stroke was followed by better cognitive status. All cognitively
      impaired stroke patients had low level of education, some had accomplished
      elementary education and others had not, all much below the dementia risk age of
      75 years. Exclusion of patients with severe stroke from the study led to
      overestimation of the results. Finally, a coherent algorithm for somatic and
      cognitive stroke assessment in stroke patients poses itself as an imperative as a
      guideline for plastic, individualized and appropriate rehabilitation.

PMID- 22649875
TI  - Educated parent as a key member of rehabilitation team.
AB  - Involvement of children with minor motor impairments in early intervention
      programs is becoming a positive trend. Rehabilitation of young children is
      usually performed in family environment with continuous monitoring by a team of
      experts including a physiatrist, speech therapist, psychologist, and
      rehabilitator. For this reason, it is important to educate parents in proper
      procedures designed to encourage the child's global and language development.
      Parental competence in encouraging the child's language development and providing
      home learning environment is associated with the level of parental education. We
      performed a retrospective analysis of data on 50 children aged 1-3 years,
      hospitalized during 2010 at Department of Pediatric Rehabilitation, University
      Department of Rheumatology, Physical Medicine and Rehabilitation, Sestre
      milosrdnice University Hospital Center in Zagreb. The aim was to determine the
      percentage of children included in an early intervention program according to the
      level of parental education and to assess the impact of the program on the
      children's language development. The results showed a higher percentage of
      parents to have high school education and a smaller percentage of parents to have
      university degree. These data indicated the need of educational programs for
      parents on the procedures of encouraging child development, including language
      development.

PMID- 22649876
TI  - Clinical course and outcome predictors in pauci-immune ANCA-positive renal
      limited vasculitis.
AB  - Our aim was to assess the clinical course and outcome of ANCA-positive, pauci
      immune renal limited vasculitis, their correlation with laboratory and
      histopathologic parameters recorded at initial and follow up testing, and to
      identify the possible outcome predictors. The study included 17 patients with
      renal biopsy, clinical, serologic and histopathologic parameters meeting the
      criteria for pauci-immune ANCA-positive glomerulonephritis without extrarenal
      manifestations of the disease. Creatinine clearance, 24-hour proteinuria and ANCA
      titer by ELISA method were determined at disease onset, during treatment and at
      the end of follow up. In 15 patients, the diagnosis was verified by kidney
      biopsy. Data were processed by Spearman correlation coefficient and Mann-Whitney
      test, and survival by Kaplan-Meier test. Lower percentage of glomeruli affected
      with vasculitis, better initial renal function as measured by serum creatinine or
      creatinine clearance, and lower chronicity on biopsy were identified as favorable
      indicators of kidney function outcome. Therapy responders had highest initial and
      lowest final 24-h proteinuria. The highest level of final 24-h proteinuria was
      recorded in dialysis dependent patients. The cumulative one-year and two-year
      patient and kidney survival rate was 64% and 50%, and 64% and 38%, respectively.

PMID- 22649877
TI  - Suicide attempts in hospital-treated epilepsy patients.
AB  - Persons suffering from epilepsy are in the group of patients at an increased
      suicide risk. The basis of every suicidal behavior, including patients suffering
      from epilepsy, is depression, and to explore the causes of suicidal behavior in
      epileptics it is necessary to find the causes responsible for the development of
      depression. Depression is caused by numerous factors divided into psychosocial
      factors, factors of the illness, and antiepileptic medication factors. The aim of
      the study was to identify the causes of suicidal behavior in epileptics treated
      in our hospital. The study included patients suffering from epilepsy treated at
      our Department from January 1 to December 31, 2009. Based on medical history,
      patients having attempted suicide were allocated to the experimental group and
      those without a history of suicidal attempt in the control group. Characteristics
      of the groups in relation to age and sex were defined first, followed by defining
      variables used in both groups, i.e. psychosocial factors (marital status,
      employment status, family environment, psychiatric comorbidity) and disease
      factors (etiology, type of seizures, duration of the disease, attitude towards
      treatment, attitude towards illness). Statistical significance was recorded in
      two psychosocial variables, i.e. family environment, which was significantly
      better in control group, and psychiatric comorbidity, which was more frequently
      present in patients having attempted suicide. Study results showed even 14.6% of
      epilepsy patients to have attempted suicide. Poor family atmosphere and
      psychiatric comorbidity had a significant role in suicidal behavior. In our
      study, the variables associated with the disease had no effect on suicidal
      behavior in epilepsy patients.

PMID- 22649878
TI  - Incidence and types of speech disorders in stroke patients.
AB  - The aim of the study was to determine the incidence and types of speech disorders
      in patients with acute stroke. The study was performed in 936 acute stroke
      patients admitted to University Department of Neurology, Tuzla University
      Clinical Center, in the period from January 1, 2007 through December 31, 2008.
      Out of 936 study patients, speech disorders were verified on admission in 771
      (82.37%) patients. Dysarthria was present in 540 (57.69%) and aphasia in 231
      (24.67%) patients. In the group with speech disturbances, dysarthria was present
      in 70.04% and aphasia in 29.96% of patients. During hospital stay, lethal outcome
      was recorded in 51 patients, significantly higher in the group with speech
      disorders (P = 0.004). At discharge from the hospital, speech disorders persisted
      in 671 (75.81%), dysarthria in 468 (69.75%), and different types of aphasia in
      203 (30.25%) of 885 surviving patients. Among patients with aphasia at both
      admission and discharge, global aphasia was most common, followed by motor
      aphasia (Broca's aphasia) and nominal aphasia. Although the rate of patients with
      speech disorders was lower at discharge, the difference was not statistically
      significant. On admission, 82.37% of patients were considered to have a speech
      language disorder, dysarthria being most common. Concerning the type of aphasia,
      global aphasia was most frequent. Study results suggested the importance and need
      of speech-language therapy in the early rehabilitation of post-stroke patients;
      it should be initiated during their hospital stay and continued at long-term.

PMID- 22649880
TI  - Mental illness and homicide--prevention of recidivism.
AB  - We hypothesized that the integration of forensic psychiatrists and the forensic
      system into the general stream of mental health should lead to better
      reintegration of forensic patients into the society. The aims of the study were
      to explore the link between violence, murder, psychiatric disorders and other
      variables, and to suggest a mode of prevention of criminal recidivism. This
      investigation provided a more reflective profile of mentally ill persons
      convicted of murder, hospitalized in Psychiatric Hospital in Demir Hisar in
      Macedonia between 2007 and 2009. Study results indicated the offender with severe
      mental illness incarcerated for murder in Demir Hisar Psychiatric Hospital to be
      predominantly suffering from a mood disorder, to be a male with secondary school
      education, and to have significant intimate and family relationships
      characterized by rage as a frequently mentioned motive for murder. On committing
      homicide, they frequently used firearm or sharp objects. The offenders lived in
      dysfunctional families, had extensive histories of substance abuse and criminal
      activity before their murder conviction, and received inadequate treatment for
      their mental disorder and substance abuse. We suggest that the offenders
      (murderers) continue their treatment in mental health forensic services upon
      completing their obligatory treatment at a psychiatric hospital.

PMID- 22649879
TI  - Analysis of the influence of various factors on anemia in patients with lymphoid
      malignancies.
AB  - Anemia is a frequent complication of lymphoid neoplasms as a result of the
      disease and myelotoxic chemotherapy, and has a significant impact on treatment
      outcome, survival and quality of life. The aim of this study was to investigate
      clinical characteristics of anemia in lymphoid malignancies and to assess the
      need of anemia treatment in the context of modern therapeutic possibilities.
      Fifty-five patients (32 female and 23 male) with non-Hodgkin's lymphoma (NHL, n =
      30), chronic lymphocytic leukemia (CLL, n = 8) and multiple myeloma (MM, n = 17)
      were included in the study. The influence of age, sex, type of malignancy and
      chemotherapy on the prevalence, severity and type of anemia before and after
      chemotherapy was analyzed. The prevalence of anemia was 51.02% before (A1) and
      55.31% after (A2) chemotherapy. Women had a higher prevalence of anemia than men
      (63% vs. 43%), but the severity was higher in men at the beginning (103 vs. 99
      g/L Hb) and at the end of treatment (101 vs. 89 g/L Hb). The highest prevalence
      of anemia was found in MM (69%), followed by NHL (44.4%) and CLL (40%) before
      chemotherapy, and in MM (68.7%), CLL (42.9%) and NHL (20.8%) after chemotherapy.
      The prevailing anemia was anemia of chronic disease (53.8%), followed by anemia
      due to multiple causes (anemia of chronic disease + iron deficiency anemia or
      anemia of chronic disease + hemolytic anemia; 30.7%), anemia due to iron
      deficiency (11.5%) and hemolytic anemia (7.6%). The prevalence of anemia as a
      consequence of the disease is high in lymphoproliferative disease, but there was
      no significant rise under chemotherapy, even showing a decline in NHL patients
      (44% vs. 21%), however, the severity of anemia increased. Since stage 1 anemia
      according to the WHO prevailed, only a small number of patients required
      transfusion therapy. About 27% of all patients had hemoglobin values <100 g/L
      during chemotherapy and could be candidates for erythropoiesis-stimulating agent
      treatment.

PMID- 22649881
TI  - The incidence of stroke at Department of Neurology, Dubrovnik General Hospital in
      2008.
AB  - Data on all patients admitted in 2008 to the Department of Neurology, Dubrovnik
      General Hospital, were retrospectively analyzed. In a total of 663 patients,
      there were 247 (37.25%) stroke patients. Ischemic stroke was diagnosed in 217
      (87.85%) and hemorrhagic stroke in 30 (12.15%) patients. In the cohort of stroke
      patients, there were 136 (55.00%) women and 111 (45.00%) men. The group of
      patients with ischemic stroke consisted of 124 (57.15%) women and 93 (42.85%)
      men, and the group of those with hemorrhagic stroke of 12 (40%) women and 18
      (60%) men. The majority of patients with ischemic stroke (89.86%) and hemorrhagic
      stroke (76.66%) were over 60 years of age. Only 9 (4.14%) patients with ischemic
      stroke and 5 (16.66%) patients with hemorrhagic stroke were employed. The
      mortality rate was 20.24% in the overall stroke group and 19.35% in the ischemic
      stroke group. In the group of patients with hemorrhagic stroke, 26.66% of
      patients died at our Department, however, additional 20% of patients with this
      type of stroke were transferred to the Hospital Intensive Care Unit or to
      Departments of Neurosurgery in Split and Zagreb, so precise data on the disease
      outcome in these patients were missing. Eighteen (7.29%) patients were from other
      countries, mostly from Bosnia and Herzegovina. The majority of them had ischemic
      stroke (83.33%) and 12 (66.66%) patients were over 60 years of age.

PMID- 22649882
TI  - Complementary and alternative treatment of musculoskeletal pain.
AB  - The use of complementary and alternative medicine (CAM) is high and increasing
      worldwide. Patients usually use CAM in addition to conventional medicine, mainly
      to treat pain. In a large number of cases, people use CAM for chronic
      musculoskeletal pain as in osteoarthritis, back pain, neck pain, or fibromyalgia.
      Herewith, a review is presented of CAM efficacy in treating musculoskeletal pain
      for which, however, no scientific research has so far provided evidence solid
      enough. In some rare cases where adequate pain control cannot be achieved, CAM
      might be considered in rational and individual approach based on the first
      general rule in medicine "not to harm" and on the utility theory of each
      intervention, i.e. according to the presumed mechanism of painful stimulus and
      with close monitoring of the patient's response. Further high quality studies are
      warranted to elucidate the efficacy and side effects of CAM methods. Therefore,
      conventional medicine remains the main mode of treatment for patients with
      musculoskeletal painful conditions.

PMID- 22649883
TI  - Prominent features of allergic angioedema on oral mucosa.
AB  - Angioedema indicates acute subcutaneous edema that characterizes improperly
      restricted cutaneous or mucous membrane swelling, which can occur only once or be
      relapsing. Edema usually occurs in the periorbital area, lips, tongue,
      extremities and intestinal wall. It has turned out that angioedema is usually
      caused by the use of angiotensin-converting enzyme inhibitors (ACE) or allergies
      to certain allergens (allergic or IgE-mediated angioedema), followed by C1
      inhibitor deficiency (hereditary and acquired angioedema), or the cause is
      unknown (idiopathic angioedema). It has been shown that patients with angioedema
      often have urticaria, which is noted in approximately 50% of cases. Usually there
      is a type I allergic reaction to some food allergens or drugs or insect stings.
      The most common causes of allergic angioedema are bee and wasp stings, reactions
      to medications or injections for sensitivity testing, and certain foods
      (especially eggs, shellfish and nuts). In diagnostic terms, it is important to
      determine the potential allergen, which is commonly performed with cutaneous
      tests, such as prick test, etc. The main risk of angioedema is swelling of the
      tongue, larynx and trachea, which can lead to airway obstruction and death,
      therefore tracheotomy is indicated in such cases. The initial treatment of
      patients with most forms of angioedema included administration of antihistamines
      and glucocorticoids, while epinephrine is given if there is fear from laryngeal
      edema.

PMID- 22649884
TI  - Head injury in children.
AB  - Nowadays, head injuries are becoming more frequent in children. The most common
      cause of head injuries in children is fall, and, in more severe injuries, traffic
      accident trauma. In traumatic brain injuries in infants and small children, the
      most common symptoms are paleness, somnolence and vomiting, the so called
      "pediatric contusion syndrome". After the first year of age, light head trauma
      occurs after minor falls, whereas the most severe injuries are caused by car
      accidents, including pedestrians, or fall from the height. As the child grows,
      severe head trauma is more likely to occur after bicycle or car accidents. Brain
      injuries involving or penetrating the brain by broken bone fragments include
      contusions and lacerations of the brain. Unconsciousness need not always occur
      during contusion, as it may also appear after swelling of the brain or high
      intracranial pressure complications. Despite comprehensive injuries in such types
      of accidents, the outcome of survivors is surprisingly good. Such severe
      neurocranium injuries usually include heavy bleeding with hematoma (epidural
      bleeding, subdural bleeding, intracerebral bleeding, and traumatic subarachnoid
      hemorrhage). Improved prehospital care, readiness and accessibility of
      multidisciplinary teams, establishment of regional centers, and efforts to
      prevent and decrease traffic accidents contribute to mortality rate reduction.

PMID- 22649885
TI  - Varicella zoster virus reactivation in hemodialysis patients: manifestations,
      treatment, complications and outcome.
AB  - Varicella zoster virus reactivation often occurs in the setting of impaired
      immunity, which is generally present in patients with end-stage renal disease
      (ESRD). Therapy for variceIla zoster virus infection is well established.
      However, it is often been forgotten that acyclovir dosage should be adjusted to
      renal function. We point to the problem encountered in clinical practice when
      ESRD patient presents with cutaneous herpes zoster and neurological symptoms.
      Clinical findings alone may prove inadequate to determine whether neurological
      deficit is caused by infection of the central nervous system or is a consequence
      of acyclovir induced neurotoxicity.

PMID- 22649886
TI  - Contact allergy in the mouth: diversity of clinical presentations and diagnosis
      of common allergens relevant to dental practice.
AB  - Delayed-type hypersensitivity reaction or type IV allergic reaction can cause
      different oral manifestations. They can be localized or diffusely visible on oral
      mucosa and usually appear 24-72 hours after antigen input. The antigens that
      cause this type of reaction are mostly external, such as contact allergens
      (particularly metals) and drugs. It has been shown that the most common oral
      manifestations are cheilitis, gingivitis, stomatitis, perioral dermatitis,
      burning mouth syndrome, lichenoid reaction and orofacial granulomatosis. The most
      important part of diagnosis is the use of patch testing that indicates contact
      allergic reaction to an allergen. The results of patch testing have shown that
      the most common proven allergens are gold, nickel, mercury, palladium, cobalt,
      acrylate, etc. Although connection between specific clinical manifestations and
      positive patch test results was not always found, patch testing is necessary to
      prove contact hypersensitivity. Therefore, in patients with oral symptoms,
      allergic hypersensitivity to dental components has to be considered.

PMID- 22649887
TI  - Glucocorticoid induced osteoporosis.
AB  - Glucocorticoid therapy is the most common cause of secondary osteoporosis and the
      leading iatrogenic cause of the disease. Often, the presenting manifestation is
      fracture, which occurs in 30% to 50% of patients receiving long-term
      glucocorticoid therapy. Glucocorticoid-induced osteoporosis predominantly affects
      regions of the skeleton that have abundant cancellous bone such as lumbar spine
      and proximal femur. Progress has been made in clarifying the pathophysiological
      mechanisms that result in glucocorticoid-induced osteoporosis. Although the
      options for prevention and treatment of glucocorticoid-induced osteoporosis
      continue to expand, provider compliance with preventive measures remains
      suboptimal.

PMID- 22649889
TI  - Basilar impression as a possible cause of cerebellar stroke: case report.
AB  - A case is reported of a 72-year-old woman who presented with severe vertigo,
      vomit, and mild neck and occipital pain. She had a medical history of
      hypertension, angina pectoris, cholelithiasis, gastric ulcer, pyelonephritis and
      periodical mild dizziness. Neuroimaging revealed right vertebral artery
      occlusion, right cerebellar stroke and basilar impression. The therapeutic
      approach chosen in our patient was conservative, with non-steroid anti
      inflammatory drugs and neck collar. Although our patient's prior risk factors for
      stroke supported a diagnosis of vertebrobasilar stroke, it is possible that the
      vertebral artery occlusion was the result of changes in the atlantoaxial anatomy
      and that cerebellar infarction was secondary to craniocervical anomaly. Although
      the presence of vertebral artery occlusion, cerebellar stroke and basilar
      impression in our patient may have been coincidental, we suggest that patients
      with basilar impression and craniocervical anomalies in general may be at an
      increased risk of vertebrobasilar vascular disease and vertebrobasilar stroke.

PMID- 22649888
TI  - Seventieth anniversary of the University Department of Rheumatology, Physical and
      Rehabilitation Medicine, School of Medicine, University of Zagreb, Sestre
      Milosrdnice University Hospital Center, Zagreb.

PMID- 22649891
TI  - Complete resolution of medically refractory temporal lobe epilepsy after
      arachnoid cyst fenestration.
AB  - Intracranial arachnoid cysts are congenital lesions that are frequently detected
      incidentally. About 30% of patients have a symptomatic epileptic seizure as the
      presenting symptom, occasionally with other focal neurologic signs. A case is
      presented of a young male patient with medically refractory temporal lobe
      epilepsy. Following his neurological examination, epileptic zone was defined in
      the right temporal lobe that correlated with the MRI-detected sylvian arachnoid
      cyst. Microneurosurgical cyst fenestration with volume reduction was performed,
      which resulted in a decremental but eventually complete seizure freedom. In
      conclusion, the arachnoid microsurgical cyst reduction is a safe procedure and
      may result in complete remission of symptomatic epileptic seizures and favorable
      outcomes, as reported in other studies.

PMID- 22649890
TI  - Mild cognitive disorder as clinical manifestation of pituitary stalk
      neurosarcoidosis: case report.
AB  - A case is presented of a 59-year-old male patient with a 5-year history of
      sarcoidosis. In the last half a year, deterioration of his intellectual abilities
      was noticed. Psychological testing detected a mild cognitive disorder. Laboratory
      diagnostics found a decreased level of testosterone and magnetic resonance
      imaging showed pituitary stalk neurosarcoidosis without any other
      pathomorphological substrate of cognitive impairment. This case indicates that
      neurosarcoidosis should be considered as a possible cause of mild cognitive
      disorder and, consequently, included in the International Classification of
      Mental and Behavioural Disorders.

PMID- 22649892
TI  - Heterotopic triplet pregnancy complicated with ovarian hyperstimulation syndrome
      following in vitro fertilization.
AB  - Heterotopic pregnancy is a rare event that occurs in less than 1% of pregnancies
      following in vitro fertilization and embryo transfer, especially when complicated
      with ovarian hyperstimulation syndrome. We report a case of a 31-year-old woman
      in the 6th gestational week of pregnancy achieved after in vitro fertilization,
      who was complaining of acute lower abdominal pain and distension, breathing
      difficulties and vaginal spotting. Transvaginal ultrasound examination and
      laboratory tests confirmed the ovarian hyperstimulation syndrome in the presence
      of two viable gestational sacs. The patient's condition worsened five days later
      with sudden onset of sharp abdominal pain, nausea and vomiting, along with
      impaired laboratory test values. Laparoscopy was attempted, but enlarged ovaries
      and adhesions prevented further procedure, which was then converted to mini
      laparotomy. Operative removal of the right tubal pregnancy resulted in
      uncomplicated course of the intrauterine twin pregnancy and delivery of two
      healthy neonates by cesarean section at 37 weeks of gestation. Clinicians need to
      be aware of this rare complication where ovarian hyperstimulation syndrome
      coexists with heterotopic pregnancy after in vitro fertilization and embryo
      transfer procedure. Enlarged ovaries may mask accurate ultrasound diagnosis, but
      timely surgical intervention can prevent fatal consequences and result in normal
      course and outcome of intrauterine pregnancy.

PMID- 22649893
TI  - Isolated right-sided heart failure in a patient with hyperthyroidism.
AB  - Hyperthyroidism has many characteristic manifestations of various organ systems.
      Cardiovascular effects are frequent in these patients. A less known complication
      of hyperthyroidism is reversible right-sided heart failure and pulmonary
      hypertension. In the patient presented, the symptoms of atrial fibrillation and
      right-sided heart failure were the first manifestations of hyperthyroidism.
      Doppler echocardiography confirmed pulmonary hypertension. Other secondary
      reasons for pulmonary hypertension were excluded. Graves' disease was the only
      reasonable choice. The treatment of hyperthyroidism resulted in conversion in
      sinus rhythm, withdrawal of symptoms and signs of right-sided heart failure, and
      normalization of pulmonary artery pressure.

PMID- 22649894
TI  - Unexpected outcome in a treated XY reversal syndrome patient.
AB  - Hormone replacement therapy is mandatory to maintain quality of life and bone
      mineralization status in patients with gonadal dysgenesis. Occasionally, these
      patients need higher than recommended estrogen dosage to prevent signs and
      symptoms of hypoestrogenic state. Our 18-year-old female patient with XY sex
      reversal syndrome was gonadectomized and administered conventional hormone
      replacement therapy. Gonadoblastoma was found in the excised streak gonad. Five
      years after continuous replacement therapy, the patient reported unexpectedly hot
      flushes and amenorrhea in spite of regular hormone intake. Severe osteopenia was
      also detected. Unconventionally high estrogen dose was given with additional
      daily vitamin D and calcium supplement. Dual energy x-ray absorptiometry revealed
      lesser but evident osteopenia and the patient reported repeated bleeding without
      hot flushes on the new hormone regimen. Individualized dosage of estrogen is
      essential for these patients according to their bone status and subjective
      symptoms. Early therapy initiation along with continuous and frequent evaluation
      of bone status and quality of life is advised.

PMID- 22649895
TI  - Repetitive stent fractures with diffuse coronary artery microaneurysm formation-
      sirolimus eluting stent hypersensitivity?
AB  - While drug eluting stents (DES) are being more widely used in ever more patients
      receiving DES each day, some new complications may be emerging. Stent fractures
      and hypersensitivity reactions to stents are among recognized complications that
      can lead to therapeutic dead end from the interventional cardiologist's point of
      view. We present a case in which we reached therapeutic dead end with a sirolimus
      eluting stent, i.e. repetitive stent fractures with diffuse microaneurysms along
      the implanted DES, possibly due to hypersensitivity reaction to parts of the
      stent.

PMID- 22649896
TI  - Development of Graves' disease following radioiodine treatment for autonomously
      functioning thyroid adenoma: case report.
AB  - A patient with development of autoimmune hyperthyroidism following radioiodine
      treatment for autonomously functioning thyroid adenoma is presented. This is a
      rare occurrence, probably as a consequence of shedding of the thyroid-stimulating
      hormone receptor, which is a source of antigen leading to activation of the
      autoimmune response in susceptible individuals.

PMID- 22649897
TI  - Headache and aphasia in a young woman with protein S deficiency and nephrotic
      syndrome.
AB  - We present sequential brain imaging findings in a young woman who while being
      evaluated for a newly discovered nephrotic syndrome developed headache followed
      by aphasia. The patient's symptoms were due to cerebral venous thrombosis in the
      setting of protein S deficiency and oral contraception.

PMID- 22649898
TI  - Malposition of central venous dialysis catheter in the right internal mammary
      vein in uremic patient: case report.
AB  - A 68-year-old Caucasian woman was admitted to the Department for construction of
      vascular access for dialysis after thrombosis of arteriovenous fistula. Temporary
      dialysis catheter was inserted in the left internal jugular vein while she had
      permanent pacemaker implanted on the right thoracic side. The patient signalized
      pain in the left breast. Postprocedural chest x-ray revealed that the catheter
      was malpositioned in the right internal mammary vein. The catheter was
      immediately pulled out and temporary catheter was inserted in the left femoral
      vein. Malposition of central venous catheter into small tributaries of central
      vein is a rare complication which can be hazardous and needs to be quickly
      recognized.

PMID- 22649899
TI  - Successful treatment of brain ischemia with supplementation therapy in a patient
      with hyperhomocysteinemia.
AB  - The effectiveness of homocysteine-lowering therapy on stroke prevention is still
      unclear. Although randomized controlled epidemiological trials have yielded mixed
      findings, a multicenter trial did not show any beneficial effect. Genetic studies
      are still lacking. Therefore, we report on a female patient with transient
      ischemic attacks and the thermolabile variant of methylenetetrahydrofolate
      reductase (TT genotype), who benefited from supplemental therapy for homocysteine
      lowering.

PMID- 22649900
TI  - Historical review. Sestre milosrdnice University Hospital 1846.

PMID- 22649901
TI  - Infant formula and adult/pediatric nutritional methods approved First Action
      using the AOAC voluntary consensus standards process.

PMID- 22649902
TI  - AOAC SMPR 2011.003: Standard method performance requirements for vitamin A in
      infant formula and adult/pediatric nutritional formula.

PMID- 22649903
TI  - AOAC SMPR 2011.004: Standard method performance requirements for vitamin D in
      infant formula and adult/pediatric nutritional formula.

PMID- 22649904
TI  - AOAC SMPR 2011.005: Standard method performance requirements for vitamin B12 in
      infant formula and adult/pediatric nutritional formula.

PMID- 22649905
TI  - AOAC SMPR 2011.006: Standard method performance requirements for folate in infant
      formula and adult/pediatric nutritional formula.

PMID- 22649906
TI  - AOAC SMPR 2011.007: Standard method performance requirements for myo-inositol in
      infant formula and adult/pediatric nutritional formula.

PMID- 22649907
TI  - AOAC SMPR 2011.008: Standard method performance requirements for nucleotides in
      infant formula and adult/pediatric nutritional formula.

PMID- 22649908
TI  - AOAC SMPR 2011.009: Standard method performance requirements for Cr, Mo, and Se
      in infant formula and adult/pediatric nutritional formula.

PMID- 22649909
TI  - Determination of folate in infant formula and adult/pediatric nutritional formula
      by optical biosensor assay: First Action 2011.05.
AB  - After a review of data from a single-laboratory validation (SLV) study published
      in the International Dairy Journal 21, 783-789 (2011), a method for folate in
      infant formula and adult/pediatric nutritional formula was submitted for
      consideration of adoption by AOAC as an automated assay that is rapid and simple.
      The method uses an optical biosensor assay to quantitate total folate content in
      milk and milk-based pediatric and adult nutritional products. The assay uses
      folate binding protein and a functionalized sensor surface. The SLV showed an
      instrumental LOD of 0.1 ng/mL (equivalent to 2.5 microg/100 g for a typical
      infant formula). The method detection limit was 6.5 microg/100 g with a
      repeatability of 3.48% and an intermediate reproducibility of 4.63% RSD.

PMID- 22649910
TI  - Determination of vitamin A in infant formula and adult nutritionals by UPLC-UV:
      First Action 2011.07.
AB  - Vitamin A, a fat-soluble vitamin, is essential for health and plays an important
      part in vision, bone growth, reproduction, regulating the immune system, cell
      function, and skin health. Due to the advances in technology and the expansion of
      its uses, LC technologies are being studied for effectiveness in detecting and
      quantifying vitamin A in an effort to help determine the amount of vitamin A in
      various types of samples. For this reason, an Expert Review Panel agreed on June
      29, 2011, at the "Standards Development and International Harmonization: AOAC
      INTERNATIONAL Mid-Year Meeting," to approve "Determination of Vitamin A in Infant
      Formula and Adult Nutritionals by UPLC-UV" as AOAC Official Method 2011.07. To
      move from First to Final Action status, it was recommended that additional
      information be generated for all types of infant formulas and adult nutritional
      formula matrixes at varied concentration levels, as indicated in the standard
      method performance requirements. International units or retinol equivalents
      typically represent the concentration of vitamin A in food and supplements.
      However, for the purpose of this method, the concentration represented is
      presented in microg/100 g.

PMID- 22649911
TI  - Determination of vitamin B12 in infant formula and adult nutritionals by liquid
      chromatography/UV detection with immunoaffinity extraction: First Action 2011.08.
AB  - At the "Standards Development and International Harmonization: AOAC INTERNATIONAL
      Mid-Year Meeting," on June 29, 2011, an Expert Review Panel agreed that the
      method "Determination of Vitamin B12 in Infant Formulas and Adult Nutritionals by
      Liquid Chromatography/UV Detection with Immunoaffinity Extraction" be adopted
      AOAC Official First Action status. The method is applicable for the determination
      of vitamin B12, which includes added cyanocobalamin and natural forms, making it
      applicable to both fortified and nonfortified products. Vitamin B12 is extracted
      from the sample in sodium acetate buffer in the presence of sodium cyanide (100
      degrees C, 30 min). After purification and concentration with an immunoaffinity
      column, vitamin B12 is determined by LC with UV detection (361 nm). A single
      laboratory validation study was conducted on a range of products, including milk-
      and soy-based infant formulas, cereals, cocoa beverages, health care products,
      and polyvitamin premixes. The method demonstrated linear response over a large
      range of concentrations, recovery rates of 100.8 +/- 7.5% (average +/- SD),
      repeatability RSD (RSDr) of 2.1%, and intermediate reproducibility (RSD(iR)) of
      4.3%. LOD and LOQ values were 0.10 and 0.30 microg/100 g, respectively, and
      correlation with the reference microbiological assay was good (R2 = 0.9442). The
      results of the study were published in J. AOAC Int. 91, 786-793 (2008). The
      performance characteristics of the method met the standard method performance
      requirements set forth by the Stakeholder Panel on Infant Formula and Adult
      Nutritionals; thus, the method was determined to be appropriate for First Action
      status.

PMID- 22649912
TI  - Determination of vitamin B12 in infant formula and adult nutritionals by HPLC:
      First Action 2011.10.
AB  - During the "Standards Development and International Harmonization: AOAC
      INTERNATIONAL Mid-Year Meeting" held on June 29, 2011, an Expert Review Panel
      (ERP) reviewed the method "Determination of Vitamin B12 in Infant Formula and
      Adult Nutritionals by HPLC." Under the new pathway to Official Methods, the ERP
      adopted the method as Official First Action. The method is applicable to the
      determination of vitamin B12 in infant formula and adult nutritionals. Data
      showed an average overall intermediate precision of 6.64% RSD, an estimated
      quantitation limit of 0.8 microg/kg, and a detection limit of 0.2 microg/kg in
      prepared samples. The standard range of the method is 2 to 200 microg/L, which
      corresponds to an analytical range of 0.8 to 500 microg/kg.

PMID- 22649913
TI  - Application of ultra-high-performance liquid chromatography/tandem mass
      spectrometry for the measurement of vitamin D in infant formula and
      adult/pediatric nutritional formula: First Action 2011.11.
AB  - In an effort to measure vitamin D, ultra-high-performance liquid chromatography
      with tandem mass spectrometry (UHPLC-MS/MS) was applied to samples. The use of
      UHPLC-MS/MS decreased the run time by 50%. The UHPLC-MS/MS achieved equal or
      better separation efficiency with complex food matrixes compared to HPLC-MS/MS.
      It was also observed that under the optimized conditions of UHPLC, all
      previtamins of vitamin D3, D2, and isotope-labeled vitamin D3 were baseline
      separated from their corresponding vitamins. The sterol isomers found in complex
      food matrixes that interfere in the analysis were well separated from the
      analytes. The accuracy of the method was evaluated by analyzing National
      Institute of Standards and Technology Standard Reference Material 1849 infant
      reference material. The average vitamin D3 concentration was 0.251 +/- 0.012
      microg/g. This showed excellent agreement with the certified value of 0.251 +/-
      0.027 microg/g. The spike recovery study of a commercial infant formula matrix
      showed a range of recovery from 100 to 108%. The LOQ values determined were
      0.0022 and 0.0028 microg/g for vitamins D3 and D2, respectively; LOD values were
      0.00065 and 0.00083 microg/g for vitamins D3 and D2, respectively.

PMID- 22649914
TI  - Determination of vitamin A (retinol) in infant formula and adult nutritionals by
      liquid chromatography: First Action 2011.15.
AB  - During the "Standards Development and International Harmonization: AOAC
      INTERNATIONAL Mid-Year Meeting," held on June 29, 2011, an Expert Review Panel
      (ERP) reviewed the method for the "Determination of Vitamins A (Retinol) and E
      (alpha-Tocopherol) in Foods by Liquid Chromatography: Collaborative Study,"
      published by Jonathan W. DeVries and Karlene R. Silvera in J. AOAC Int. in 2002.
      After evaluation of the original validation data, an ERP agreed in June 2011 that
      the method meets standard method performance requirements (SMPRs) for vitamin A,
      as articulated by the Stakeholder Panel on Infant Formula and Adult Nutritionals.
      The ERP granted the method First Action status, applicable to determining vitamin
      A in ready-to-eat infant and adult nutritional formula. In an effort to achieve
      Final Action status, it was recommended that additional information be generated
      for different types of infant and adult nutritional formula matrixes at varied
      concentration levels as indicated in the vitamin A (retinol) SMPR. Existing AOAC
      LC methods are suited for specific vitamin A analytical applications. The
      original method differs from existing methods in that it can be used to assay
      samples in all nine sectors of the food matrix. One sector of the food matrix was
      powdered infant formula and gave support for the First Action approval for
      vitamin A in infant and adult nutritional formula. In this method, standards and
      test samples are saponified in basic ethanol-water solution, neutralized, and
      diluted, converting fats to fatty acids and retinol esters to retinol. Retinol is
      quantitated by an LC method, using UV detection at 313 or 328 nm for retinol.
      Vitamin concentration is calculated by comparison of the peak heights or peak
      areas of retinol in test samples with those of standards.

PMID- 22649915
TI  - Determination of vitamin B12 in infant formula and adult nutritionals by surface
      plasmon resonance: First Action 2011.16 (test kit method).
AB  - At the "Standards Development and International Harmonization: AOAC INTERNATIONAL
      Mid-Year Meeting" on June 29, 2011, an Expert Review Panel (ERP) agreed to
      further examine AOAC Official Method 2011.01, "Determination of Vitamin B12 by
      Surface Plasmon Resonance," for use with infant formula and adult nutritionals.
      The original collaborative study was conducted using the Biacore Q biosensor
      instrument and the Biacore Q Qflex Kit Vitamin B12 PI. Samples included in the
      study were infant formula, cereals, premixes, vitamin tablets, dietary
      supplements, and baby food. Eleven laboratories participated in the collaborative
      study. The results demonstrated a repeatability RSD (RSDr) of 1.59-27.8 and
      HorRat values for reproducibility of 0.34-1.89 in samples with levels ranging
      from ppm to ppb. The assay studied is a label-free protein binding-based assay
      that uses the principle of surface plasmon resonance to measure the interaction
      between vitamin B12 and a specific binding protein by passing a portion of the
      prepared sample extract combined with binding protein solution across a
      functionalized sensor chip. The response from the functionalized sensor chip is
      given as free-binding protein, as the mixture binds to the prepared surface of
      the chip. The ready-to-use Qflex Kit Vitamin B12 PI provides the reagents and
      accessories necessary to perform this assay. AOAC Method 2011.01 was approved by
      the AOAC Method Committee on Food Nutrition for Official First Action status,
      applicable to a wide range of food products, dietary supplements, and
      multivitamin premixes. After evaluation of the validation data available, an ERP
      agreed in June 2011 that the method meets standard method performance
      requirements, as articulated by the Stakeholder Panel on Infant Formula and Adult
      Nutritionals. The ERP granted the method First Action status, applicable to
      infant formula and adult/pediatric nutritional formula.

PMID- 22649916
TI  - Gluten--current status and new analytical developments in support of the
      regulatory requirements.

PMID- 22649917
TI  - Gluten and gluten-free: issues and considerations of labeling regulations,
      detection methods, and assay validation.
AB  - Gluten is a commonly used cereal derivative found in bakery products, among other
      items. In some susceptible individuals, however, it triggers immune responses of
      different kinds; there is, to a lesser extent, the wheat allergy that is
      immunoglobulin E (IgE)-mediated and leads to histamine release and typical
      allergic symptoms. In this case, other water-soluble proteins, like albumins, are
      also involved. On the other hand, there is, more frequently, celiac disease (CD),
      where the gluten causes immune reactions in the intestines of certain
      individuals, leading to degeneration of villi, which typically leads to
      malabsorption of nutrients and, consequently, malnutrition. The only currently
      effective health strategy for affected consumers is avoidance of gluten
      containing products, based on clear labeling rules. However, despite unanimously
      accepted Codex definitions by all member jurisdictions, the national
      implementation of equivalent laws shows significant differences. In the context
      of CD and in support of the gluten-free statement, regulatory enforcement, as
      well as manufacturers' quality controls are mostly based on analytical results.
      However, numerous methods are available, some of which have been validated better
      than others, and many provide different results on identical samples. Reasons
      include detection of different gluten components and variability in extraction
      efficiency due to different buffer compositions, especially from processed foods.
      Last but not least, the lack of reference materials is hindering the process of
      generating comparable data across different ELISA kits, as well as other methods.
      How can such data still be used to support a gluten-free claim? New
      methodologies, in particular mass spectrometric analysis of gluten derived
      peptides, are being introduced in numerous laboratories. This methodology is not
      only capable of detecting gluten derived peptides but can also differentiate
      between and quantitate wheat, barley, rye, and oat. This paper presents
      analytical limitations, as well as promising new approaches in support of
      industry and enforcement activities to ensure compliance with the gluten-free
      claim under the current regulatory framework.

PMID- 22649918
TI  - Gluten and celiac disease--an immunological perspective.
AB  - Gluten, a complex protein group in wheat, rye, and barley, causes celiac disease
      (CD), an autoimmune enteropathy of the small intestine, in genetically
      susceptible individuals. CD affects about 1% of the general population and causes
      significant health problems. Adverse inflammatory reactions to gluten are
      mediated by inappropriate T-cell activation leading to severe damage of the
      gastrointestinal mucosa, causing atrophy of absorptive surface villi. Gluten
      peptides bind to the chemokine receptor, CXCR3, and induce release of zonulin,
      which mediates tight-junction disassembly and subsequent increase in intestinal
      permeability. Proinflammatory cytokine IL-15 also contributes to the pathology of
      CD, by driving the expansion of intra-epithelial lymphocytes that damage the
      epithelium and promote the onset of T-cell lymphomas. There is no cure or
      treatment for CD, except for avoiding dietary gluten. Current gluten thresholds
      for food labeling have been established based on the available analytical
      methods, which show variation in gluten detection and quantification. Also, the
      clinical heterogeneity of celiac patients poses difficulty in defining clinically
      acceptable gluten thresholds in gluten-free foods. Presently, there is no
      bioassay available to measure gluten-induced immunobiological responses. This
      review focuses on various aspects of CD, and the importance of gluten thresholds
      and reference material from an immunological perspective.

PMID- 22649919
TI  - Detoxification of gluten by means of enzymatic treatment.
AB  - Celiac disease (CD) is an inflammatory disease of the upper small intestine in
      genetically predisposed individuals caused by glutamine- and proline-rich
      peptides from cereal storage proteins (gluten) with a minimal length of nine
      amino acids. Such peptides are insufficiently degraded by gastrointestinal
      enzymes; they permeate the lymphatic tissue, are bound to celiac-specific,
      antigen-presenting cells, and stimulate intestinal T-cells. The typical clinical
      pattern is a flat small intestinal mucosa and malabsorption. Currently, the only
      therapy is a strict, lifelong gluten-free diet. Recent research has shown that
      gluten and gluten peptides can be degraded by prolyl endopeptidases from
      different sources. These peptidases can either be used to produce gluten-free
      foods from gluten-containing raw materials, or they have been suggested as an
      oral therapy for CD, in which dietary gluten is hydrolyzed by coingested
      peptidases already in the stomach, thus preventing CD-specific immune reactions
      in the small intestine. This would be an alternative for CD patients to the
      gluten-free diet. Furthermore, microbial transglutaminase could be used to
      detoxify gluten either by selectively modifying glutamine residues of intact
      gluten by transamidation with lysine methyl ester or by crosslinking gluten
      peptides in beverages via isopeptide bonds so that they can be removed by
      filtration.

PMID- 22649920
TI  - Immunoreactivity and detection of wheat proteins by commercial ELISA kits.
AB  - Wheat proteins are responsible for sensitivities, including baker's asthma,
      immunoglobulin E (IgE)-mediated allergic reaction, wheat-dependent, exercise
      induced anaphylaxis, and celiac disease. The detection of gluten/wheat traces in
      foods is important to safeguard the health of wheat-sensitive individuals and
      comply with food labeling. Many immunoanalytical-based commercial kits are
      available for the quantification of gliadin/gluten/wheat proteins. We compared
      the immunoreactivity of wheat fractions with wheat-allergic human serum IgE and
      antibody conjugates used in six commercial immunoassay kits. Moreover, the
      performance of the kits was tested using corn flour spiked with gluten (5, 10,
      25, and 50 ppm) and wheat flour (50, 100, 250, and 500 ppm). The albumin,
      globulin, gliadin, and glutenin fractions reacted with IgE from nine, eight, two,
      and eight patients' sera, respectively, out of nine wheat allergic patients
      tested. Among the antibodies from commercial kits, those from R-Biopharm,
      Morinaga, and Romer Labs reacted strongly with the gliadin fraction, whereas
      those from BioKits, ALLER-TEK, and ELISA Systems reacted strongly with the
      glutenin fraction. All kits showed minimal or no reactivity with albumin and
      globulin fractions. All kits detected the gluten and wheat flour in a corn flour
      matrix at the lowest spiked levels of 5 and 50 ppm, respectively. However, there
      was wide variation among the kits when comparing the recovery of gluten and wheat
      flour. The recovery was also dependent on the source material (gluten or wheat
      flour) used for spiking the corn flour matrix.

PMID- 22649921
TI  - Characterization of G12 sandwich ELISA, a next-generation immunoassay for gluten
      toxicity.
AB  - In this work, a monoclonal antibody called G12, raised against the most
      immunotoxic peptide to celiac disease patients, was used to develop a sandwich
      ELISA. Preliminary results on cross-reactivities, recoveries, and extraction
      methods of the new assay are presented. The assay calibration was performed using
      material from the Prolamin Working Group. The antibody's specificity was
      determined by crossreactivity studies on different grains, nuts, oils, and
      starches. Recovery of the assay was determined by spiking experiments on common
      food matrixes, as well as on problematic matrixes. Furthermore, sample extraction
      methods using ethanol, cocktail solution, and a proprietary buffer have been
      compared.

PMID- 22649922
TI  - Gluten fragment detection with a competitive ELISA.
AB  - The second generation of a competitive ELISA for prolamin quantification based on
      the R5 antibody was studied for method performance and suitability to detect
      partially hydrolyzed prolamins in food. To be able to convert signal intensities
      to gluten concentrations, as required by the Codex Alimentarius Standard, a new
      calibrator consisting of a peptic-tryptic digest of wheat, rye, and barley
      prolamins was used for the first time. LOD and LOQ of the assay were 1.36 and 5.0
      mg prolamin/kg food, respectively. Analysis of beer samples and a hydrolyzed
      wheat product showed that the assay provided significantly higher prolamin
      concentrations, compared to the sandwich ELISA based on the same antibody, which
      is only suitable for the detection of intact prolamins. Spiking experiments with
      defined concentrations of partially hydrolyzed prolamins gave recoveries ranging
      from 92 to 136%.

PMID- 22649923
TI  - Development of incurred reference material for improving conditions of gluten
      quantification.
AB  - Celiac disease and wheat allergy are the most common adverse reactions triggered
      by cereal proteins, mainly gluten, which is one of the 14 allergenic food
      ingredients that must be labeled on food products in the European Union (EU). To
      meet the requirements of this regulation, reliable analytical methodology for
      proper quantification of gluten is necessary. However, validation of presently
      used methods (ELISA and lateral flow device) is limited partly due to the lack of
      reference methods and incurred reference materials. To solve this problem, the
      goal of our work was to develop an incurred reference material for the
      quantification of gluten under the auspices of EU-FP6 funded Network of
      Excellence MoniQA. During this work, we produced a processed model product
      (cookie) containing gliadin (major allergenic fraction of gluten) in a defined
      amount. This paper addresses the development process of this material together
      with the associated problems (insufficient homogeneity and low recovery) and
      their solutions. As a result, an incurred food matrix was produced on a
      laboratory-scale with a potential use as a reference material. The model product
      was tested by an ELISA method followed by a comparative study of commercially
      available ELISA kits to investigate the applicability of the product. Preliminary
      results of this study are also presented.

PMID- 22649924
TI  - Influence of sample extraction solutions on the detection of wheat proteins by
      mass spectrometry.
AB  - Routinely used methods for the detection of gluten mostly use denaturing agents
      and high salt concentrations to increase the extractability of the gluten
      fraction. These work well in combination with ELISA methods, but may have a
      negative effect on MS methods due to their influence on the ionization of the
      analyte leading to a significant reduction of signal intensities. A newly
      developed HPLC/MS/MS method was used to assess this influence. Four different
      extraction buffers were compared: 70% ethanol, TRIS-HCl, TRIS-HCl with
      dithiothreitol, and a commercially available cocktail solution. Unprocessed and
      processed wheat samples were analyzed. When analyzing unprocessed samples, a
      negative effect on ionization could be observed. Considering extraction
      capabilities and signal intensities, TRIS-HCl seemed to be the most suitable
      buffer in combination with the MS method. To assess whether the method was
      capable of detecting hidden wheat protein in different kinds of food, different
      food samples containing 0 to 34000 microg/g gluten were analyzed using the TRIS
      HCI extraction buffer.

PMID- 22649925
TI  - Determination of naturally occurring formaldehyde levels in sap and wood tissue
      of maple trees using gas chromatgraphy/mass spectrometry.
AB  - The occurrence of formaldehyde in sap and wood tissue of treated and untreated
      maple sugar trees was investigated using GC/MS. Samples were collected at
      different periods of the 2009 season and at different locations in Quebec,
      Canada. The natural concentration of formaldehyde found in untreated samples
      varied according to periods and locations and ranged from below the LOQ to 1.82
      mg/kg for sap samples and from 2.39 to 8.92 mg/kg of fresh tissue for wood
      samples. Late season samples tended to have higher concentrations of
      formaldehyde. Samples of sap and wood tissue from tapholes treated with solutions
      of formaldehyde showed increased concentrations of formaldehyde for many days
      after treatment and were clearly distinct from untreated samples. These results
      will be useful to elaborate new inspection procedures for sugarbushes to control
      the illegal use of formaldehyde.

PMID- 22649926
TI  - Development and validation of a reversed-phase HPLC method for determination of
      alkaloids from Papaver somniferum L. (Papaveraceae).
AB  - An HPLC method for the separation of six target alkaloids from Papaver somniferum
      L. (morphine, codeine, oripavine, thebaine, papaverine, and noscapine) was
      developed, optimized, and validated. The chromatographic behavior of these
      alkaloids was investigated using a reversed-phase chromatography at acidic and
      alkaline pH. The effects of ion-pairing agents, pH value of the mobile phase,
      concentration of the buffer components, mobile phase organic modifier, and column
      temperature were studied. Regardless of the large differences in their pKa
      values, all alkaloids were separated within a close retention window, and good
      peak shape was achieved for each of the six alkaloids. The proposed method has
      adequate selectivity, linearity, accuracy, precision, and reproducibility and is
      applicable for poppy straw.

PMID- 22649927
TI  - Should the AOAC use-dilution method be continued for regulatory purposes?
AB  - Despite its very poor reproducibility, AOAC INTERNATIONAL's use-dilution method
      (UDM) for bactericidal activity (AOAC Methods 964.02, 955.14, and 955.15) has
      been required by the U.S. Environmental Protection Agency (EPA) since 1953 for
      regulatory purposes, while methods with better reproducibility have been adopted
      in Canada and Australia. This study reviews UDM from a statistical perspective.
      Additionally, the test's expected results were compared to those obtained from
      actual evaluation of several formulations. Significant gaps have been identified
      in the reproducibility of the test data as predicted by statistical analysis and
      those presented to the EPA for product registration. UDM's poor reproducibility,
      along with its qualitative nature, requires the concentration of the active
      ingredient to be high enough to ensure all or most carriers to be free of any
      viable organisms. This is not in accord with the current trends towards
      sustainability, human safety, and environmental protection. It is recommended
      that the use of the method for regulatory purposes be phased out as soon as
      possible, and methods with better design and reproducibility be adopted instead.

PMID- 22649928
TI  - Determination of phenols and phenates in disinfectant formulations by liquid
      chromatography with UV detection: collaborative study.
AB  - Fourteen collaborating laboratories assayed o-phenylphenol (OPP), p-t-amylphenol
      (PTAP), and o-benzyl-p-chlorophenol (OBPCP) in formulated products, both ready-to
      use and concentrates, by RP-HPLC. The actives in the samples ranged from 0.03 to
      11% OPP, 0.06 to 4% PTAP, and 0.07 to 10% OBPCP either in free forms or as salts.
      Seven blind duplicates were analyzed. The samples were diluted/extracted with
      acidified methanol, filtered, and analyzed by LC on a C18 column using gradient
      elution and UV detection at 285 nm. The concentration of the active ingredients
      was calculated from a standard curve. Each laboratory weighed each test sample
      twice within a single analytical run. The data were analyzed using all 14
      laboratory results, with appropriate statistical tests to detect outliers. The
      repeatability RSDs ranged from 0.98 to 3.40% for the free phenols, and 1.26 to
      2.51% for the salts. The reproducibility RSDs ranged from 5.31 to 7.80% for the
      free phenols, and 5.50 to 8.67% for the salts. The HorRat ranged from 0.86 to
      2.17 for the free phenols, and 1.54 to 2.72 for the salts.

PMID- 22649929
TI  - Simultaneous determination of atorvastatin calcium, ezetimibe, and fenofibrate in
      a tablet formulation by HPLC.
AB  - An accurate, simple, reproducible, and sensitive HPLC method was developed and
      validated for the simultaneous determination of atorvastatin calcium, ezetimibe,
      and fenofibrate in a tablet formulation. The analyses were performed on an RP C18
      column, 150 x 4.60 mm id, 5 pm particle size. The mobile phase methanol
      acetonitrile-water (76 + 13 + 11, v/v/v), was pumped at a constant flow rate of 1
      mL/min. UV detection was performed at 253 nm. Retention times of atorvastatin
      calcium, ezetimibe, and fenofibrate were found to be 2.25, 3.68, and 6.41 min,
      respectively. The method was validated in terms of linearity, precision,
      accuracy, LOD, LOQ, and robustness. The response was linear in the range 2-10
      microg/mL (r2 = 0.998) for atorvastatin calcium, 2-10 microg/mL (r2 = 0.998) for
      ezetimibe, and 40-120 microg/mL (r2 = 0.998) for fenofibrate. The developed
      method can be used for routine quality analysis of the drugs in the tablet
      formulation.

PMID- 22649930
TI  - Reveal Listeria 2.0 test for detection of Listeria spp. in foods and
      environmental samples.
AB  - A Performance Tested Method validation study was conducted for a new lateral flow
      immunoassay (Reveal Listeria 2.0) for detection of Listeria spp. in foods and
      environmental samples. Results of inclusivity testing showed that the test
      detects all species of Listeria, with the exception of L. grayi. In exclusivity
      testing conducted under nonselective growth conditions, all non-listeriae tested
      produced negative Reveal assay results, except for three strains of Lactobacillus
      spp. However, these lactobacilli are inhibited by the selective Listeria
      Enrichment Single Step broth enrichment medium used with the Reveal method. Six
      foods were tested in parallel by the Reveal method and the U.S. Food and Drug
      Administration/Bacteriological Analytical Manual (FDA/BAM) reference culture
      procedure. Considering data from both internal and independent laboratory trials,
      overall sensitivity of the Reveal method relative to that of the FDA/BAM
      procedure was 101%. Four foods were tested in parallel by the Reveal method and
      the U.S. Department of Agriculture-Food Safety and Inspection Service (USDA-FSIS)
      reference culture procedure. Overall sensitivity of the Reveal method relative to
      that of the USDA-FSIS procedure was 98.2%. There were no statistically
      significant differences in the number of positives obtained by the Reveal and
      reference culture procedures in any food trials. In testing of swab or sponge
      samples from four types of environmental surfaces, sensitivity of Reveal relative
      to that of the USDA-FSIS reference culture procedure was 127%. For two surface
      types, differences in the number of positives obtained by the Reveal and
      reference methods were statistically significant, with more positives by the
      Reveal method in both cases. Specificity of the Reveal assay was 100%, as there
      were no unconfirmed positive results obtained in any phase of the testing.
      Results of ruggedness experiments showed that the Reveal assay is tolerant of
      modest deviations in test sample volume and device incubation time.

PMID- 22649931
TI  - AES chemunex ADIAFOOD detection system for Listeria spp. environmental sample
      testing.
AB  - The ADIAFOOD Detection System for the detection of Listeria species from
      environmental surfaces is based on real-time PCR technology and allows rapid
      pathogen detection within 21 h. The strength of the ADIAFOOD technology resides
      in its ability to rapidly and accurately detect Listeria species present on
      surfaces, such as stainless steel, plastic, ceramic, and sealed concrete. The
      technology is easy to use and versatile.

PMID- 22649932
TI  - Efficient isolation and identification of Bacillus cereus group.
AB  - Bacillus cereus is a group of ubiquitous facultative anaerobic sporeforming Gram
      positive rods commonly found in soil. The spores frequently contaminate a variety
      of foods, including produce, meat, eggs, and dairy products. Foodborne illnesses
      associated with toxins produced by B. cereus can result in self-limiting diarrhea
      or vomiting. Plate enumeration methods recommended by recognized food authorities
      to detect the presence of B. cereus in potentially contaminated food products do
      not inhibit other Gram-positive competitive bacteria. This study evaluated the
      use of Bacara, a new chromogenic agar, as an efficient method to identify and
      enumerate B. cereus group from food matrixes, even in the presence of background
      flora. Inclusivity and exclusivity testing was performed using four different
      selective and differential media for B. cereus, including Mannitol Egg Yolk
      Polymyxin (MYP), Polymyxin Pyruvate Egg-Yolk Mannitol Bromothymol Blue Agar,
      Bacillus Chromogenic Media, Brilliance, and Bacara. MYP and Bacara were also used
      in plate enumeration studies to isolate B. cereus from artificially contaminated
      foods.

PMID- 22649933
TI  - Comparison of slurry mixing and dry milling in laboratory sample preparation for
      determination of ochratoxin A and deoxynivalenol in wheat.
AB  - The significance of laboratory sample preparation for the determination of two
      important mycotoxins, ochratoxin A (OTA) and deoxynivalenol (DON), in wheat was
      investigated by comparing water-slurry mixing and dry-milling procedures. The
      distribution of OTA and DON in 10 kg samples of naturally contaminated wheat was
      established by analyzing one hundred 100 g subsamples of each sample. A normal
      distribution and a good repeatability of DON measurements was observed for both
      water-slurry mixing (mean 2290 microg/kg, CV 4.6%, median 2290 microg/kg) and dry
      milling (mean 2310 microg/kg, CV 6.4%, median 2290 microg/kg) procedures. For OTA
      determinations, reliable results could be obtained only by slurry mixing sample
      preparation (mean 2.62 microg/kg, CV 4.0%, median 2.62 microg/kg), whereas dry
      milling comminution resulted in an inhomogeneous distribution with a high
      variability (mean 0.83 microg/kg, CV 75.2%, median 0.60 microg/kg) and a positive
      skewness (2.12). Ad hoc experiments were performed on different size portions of
      the same sample (10 kg) to assess accuracy and precision of the
      comminution/homogenization procedures (slurry mixing and dry milling). Very good
      results were obtained for DON determination with both procedures in terms of
      accuracy (>98.7% of the "weighted value") and precision (CV <3%). For OTA
      determination good results were only obtained by slurry mixing (99.4% of the
      "weighted value," CV 10%), whereas dry milling provided results with low accuracy
      (43.2% of the "weighted value") and high variability (CV 110%). This study
      clearly demonstrated that sample preparation by slurry mixing is strictly
      necessary to obtain reliable laboratory samples for OTA determination in wheat to
      minimize misclassification of acceptable/rejectable lots, mainly within official
      control.

PMID- 22649934
TI  - Determination of volatile compounds in wine by gas chromatography-flame
      ionization detection: comparison between the U.S. Environmental Protection Agency
      3sigma approach and Hubaux-Vos calculation of detection limits using ordinary and
      bivariate least squares.
AB  - A capillary GC-flame ionization detection (FID) method to determine volatile
      compounds (ethyl acetate, 1,1-diethoxyethane, methyl alcohol, 1-propanol, 2
      methyl-1-propanol, 2-methyl-1-butanol, 3-methyl-1-butanol, 1-butanol, and 2
      butanol) in wine was investigated in terms of calculation of detection limits and
      calibration method. The main objectives were: (1) calculation of regression
      coefficient parameters by ordinary least-squares (OLS) and bivariate least
      squares (BLS) regression models, taking into account errors in both axes; (2)
      estimation of linear dynamic range (LDR) according to International Conference on
      Harmonization recommendations; (3) performance evaluation of a method by using
      three different internal standards (ISs) such as acetonitrile, acetone, and 1
      pentanol; (4) evaluation of LODs according to the U.S. Environmental Protection
      Agency (EPA) 3sigma approach and the Hubaux-Vos (H-V) method; (5) application of
      H-V theory to a gas chromatographic analytical method and to a food matrix; and
      (6) accuracy assessment of the method relative to methyl alcohol content through
      a Unione Italiana Vini (UIV) interlaboratory proficiency test. Calibration curves
      calculated via BLS and OLS show similar slopes, while intercepts are closer to
      zero in the first case, independent of the chosen IS. The studied ISs show a
      substantially equivalent behavior, even though the IS closer to the analyte
      retention time seems to be more appropriate in terms of LDR and LOD. Results
      indicate an underestimation of LODs using the EPA 3sigma approach instead of the
      more realistic H-V method, both with OLS and BLS regression models. Methanol
      contents compared with UIV average values indicate recovery between 90 and 110%.

PMID- 22649935
TI  - Determination of total cholesterol in meat and poultry by gas chromatography:
      single-laboratory validation.
AB  - The primary objective of this study was to determine the intralaboratory
      performance of a cholesterol determination method that combines direct
      saponification of a 1 g meat or poultry sample and GC quantification of liberated
      cholesterol without derivatization. Cholesterol was detected at 11.96 min using a
      GC-flame ionization detector (FID) system. With a 0.005 mg/mL 5alpha-cholestane
      internal standard and 0.008 to 0.020 mg/mL cholesterol standard series, the FID
      response was linearly correlated to standard concentrations with a coefficient of
      determination of 0.995 and a response factor of 0.66. The LOD and LOQ were 1.24
      and 4.00 mg/100 g, respectively. Cholesterol could be analyzed within 6 days of
      preparation with high precision (CV of 0.92 to 2.69%) and accuracy (recovery of
      93.24 to 100.56%). This simplified procedure allows for decreased errors and
      increased productivity, and the method proved to be reliable and able to
      withstand practical variation in procedural application. The method has been
      applied routinely with excellent precision to update data on the cholesterol
      content of beef, pork, and chicken in the U.S. Department of Agriculture National
      Nutrient Database for Standard Reference.

PMID- 22649936
TI  - WEFTA interlaboratory comparison on total lipid determination in fishery products
      using the Smedes method.
AB  - Lipid determination by the Smedes method was tested in an interlaboratory trial
      performed by nine laboratories from seven countries belonging to the West
      European Fish Technologists Association Analytical Methods Working Group. Five
      samples of fish and fishery products with different lipid contents, including two
      blind duplicates, were distributed among the participants. All laboratories
      applied a slightly modified Smedes method, which included extraction of lipids by
      cyclohexane and isopropanol, transfer of lipids to the cyclohexane phase by
      addition of water, phase separation by centrifugation, and gravimetric lipid
      determination. The results indicate that the RSD for reproducibility (RSD(R)) was
      between 4.11 and 6.31% for samples with moderate (7%) and high (14%) lipid
      content, depending on the sample. Larger SDs among the laboratories were obtained
      for a cod sample with low lipid content of 0.5%. The method is judged to be
      suitable as a routine method for lipid determination in fish and fishery
      products.

PMID- 22649937
TI  - Quantification of meat proportions by measuring DNA contents in raw and boiled
      sausages using matrix-adapted calibrators and multiplex real-time PCR.
AB  - The quantification of meat proportions in raw and boiled sausage according to the
      recipe was evaluated using three different calibrators. To measure the DNA
      contents from beef, pork, sheep (mutton), and horse, a tetraplex real-time PCR
      method was applied. Nineteen laboratories analyzed four meat products each made
      of different proportions of beef, pork, sheep, and horse meat. Three kinds of
      calibrators were used: raw and boiled sausages of known proportions ranging from
      1 to 55% of meat, and a dilution series of DNA from muscle tissue. In general,
      results generated using calibration sausages were more accurate than those
      resulting from the use of DNA from muscle tissue, and exhibited smaller
      measurement uncertainties. Although differences between uses of raw and boiled
      calibration sausages were small, the most precise and accurate results were
      obtained by calibration with fine-textured boiled reference sausages.

PMID- 22649938
TI  - Method for the determination of catechin and epicatechin enantiomers in cocoa
      based ingredients and products by high-performance liquid chromatography: single
      laboratory validation.
AB  - A single-laboratory validation study was performed for an HPLC method to identify
      and quantify the flavanol enantiomers (+)- and (-)-epicatechin and (+)- and (-)
      catechin in cocoa-based ingredients and products. These compounds were eluted
      isocratically with an ammonium acetate-methanol mobile phase applied to a
      modified beta-cyclodextrin chiral stationary phase and detected using
      fluorescence. Spike recovery experiments using appropriate matrix blanks, along
      with cocoa extract, cocoa powder, and dark chocolate, were used to evaluate
      accuracy, repeatability, specificity, LOD, LOQ, and linearity of the method as
      performed by a single analyst on multiple days. In all samples analyzed, (-)
      epicatechin was the predominant flavanol and represented 68-91% of the total
      monomeric flavanols detected. For the cocoa-based products, within-day (intraday)
      precision for (-)-epicatechin was between 1.46-3.22%, for (+)-catechin between
      3.66-6.90%, and for (-)-catechin between 1.69-6.89%; (+)-epicatechin was not
      detected in these samples. Recoveries for the three sample types investigated
      ranged from 82.2 to 102.1% at the 50% spiking level, 83.7 to 102.0% at the 100%
      spiking level, and 80.4 to 101.1% at the 200% spiking level. Based on performance
      results, this method may be suitable for routine laboratory use in analysis of
      cocoa-based ingredients and products.

PMID- 22649939
TI  - Comprehensive GMO detection using real-time PCR array: single-laboratory
      validation.
AB  - We have developed a real-time PCR array method to comprehensively detect
      genetically modified (GM) organisms. In the method, genomic DNA extracted from an
      agricultural product is analyzed using various qualitative real-time PCR assays
      on a 96-well PCR plate, targeting for individual GM events, recombinant DNA (r
      DNA) segments, taxon-specific DNAs, and donor organisms of the respective r-DNAs.
      In this article, we report the single-laboratory validation of both DNA
      extraction methods and component PCR assays constituting the real-time PCR array.
      We selected some DNA extraction methods for specified plant matrixes, i.e., maize
      flour, soybean flour, and ground canola seeds, then evaluated the DNA quantity,
      DNA fragmentation, and PCR inhibition of the resultant DNA extracts. For the
      component PCR assays, we evaluated the specificity and LOD. All DNA extraction
      methods and component PCR assays satisfied the criteria set on the basis of
      previous reports.

PMID- 22649940
TI  - Rapid method for the determination of vitamins A and E in foods using ultra-high
      performance liquid chromatography.
AB  - A rapid and novel ultra-HPLC (u-HPLC) method for the determination of vitamins A
      (retinol) and E (alpha-, gamma-, and delta-tocopherol) in foods was validated in
      terms of its precision, accuracy, and linearity. The u-HPLC separation was
      performed on an RP C18 column (particle size 2 microm, id 2 mm, and length 75
      mm), followed by fluorescence detection. The recovery of retinol was more than
      84.58%; the LOD and LOQ of the u-HPLC analysis were 0.015 and 0.045 mg/kg,
      respectively. The intraday and interday precision was less than 9.12%. The
      recoveries of alpha-, gamma-, and delta-tocopherol were more than 81.37%; the LOD
      and the LOQ were 0.014, 0.002, and 0.001 mg/kg and 0.042, 0.005, and 0.004 mg/kg,
      respectively. All calibration curves had good linearity (r2 = 0.99) within the
      test ranges. The novel, rapid method coupled to u-HPLC can provide significant
      improvements in the speed, sensitivity, and resolution compared with a
      conventional HPLC method.

PMID- 22649941
TI  - Determination of streptomycin residue in cucumber and Chinese cabbage by high
      performance liquid chromatography with postcolumn derivatization and fluorometric
      detection.
AB  - A sensitive and accurate method was developed for the determination of
      streptomycin using HPLC followed by postcolumn derivatization and fluorometric
      detection. The analyte was extracted, using aqueous solution from cucumber and
      Chinese cabbage, by a two-step SPE procedure. The extraction, cleanup, and
      chromatography conditions were optimized, and the performance of the analysis
      method was evaluated. The conditions of chromatography were as follows: the
      separation was performed on a C18 column; the isocratic mobile phase consisted of
      acetonitrile and a mixed solution containing 10 mM sodium 1,2-naphthoquinone-4
      sulfonate and 0.4 mM sodium 1-heptanesulfonate (25+75, v/v); and the flow rate
      was 1 mL/min. The fluorescence detector was set at an excitation wavelength of
      263 nm and an emission wavelength of 435 nm. The calibration curve was linear
      over the range of 50-2000 ng/mL, with a correlation coefficient of 0.9995. The
      LOD and LOQ were 10 and 30 ng/g, respectively, in both cucumber and Chinese
      cabbage. The method was validated for selectivity, linearity, precision, and
      accuracy. The intraday and interday precision and accuracy were within 10%. The
      mean recoveries from spiked samples were more than 75%, with RSD lower than 10%.

PMID- 22649942
TI  - Study of high-resolution mass spectrometry technology as a replacement for tandem
      mass spectrometry in the field of quantitative pesticide residue analysis.
AB  - A validated LC/MS/MS-based multiresidue pesticide method was converted to an LC
      high-resolution MS single-stage Orbitrap platform. No changes regarding the
      cleanup and LC were made. Optimization of high-resolution MS-specific parameters
      and interface settings was kept at a minimum. The aim was to explore the
      capability of current Orbitrap technology to substitute for LC/MS/MS technology.
      The test included the quantitative performance (sensitivity, selectivity,
      linearity, accuracy, and precision) of some 240 analytes in three different
      matrixes. The LC/MS/MS instrumentation was operated at the edge of its technical
      limitations. A further extension of the number of analytes for LC/MS/MS would
      require the use of even narrower dwell times, significantly reducing sensitivity
      and reproducibility of measurement. No such limitations exist for the high
      resolution technology. Similar performance was observed for both technologies. A
      current drawback of the high-resolution technology is the speed of data
      processing, which took significantly longer than for LC/MS/MS data due to the
      limited capabilities of the software.

PMID- 22649943
TI  - Evaluation of headspace solid-phase microextraction for analysis of phosphine
      residues in wheat.
AB  - In headspace (HS) analysis, a fumigant is released from a commodity into a gas
      tight container by grinding, heating, or microwaves. A new technique uses HS
      solid-phase microextraction (SPME) for additional preconcentration of fumigant.
      HS-SPME was tested for detection of phosphine (PH3), chosen for examination
      because of its wide use on stored commodities. PH3 was applied to 50 g wheat in
      separate 250 mL sealed flasks, which were equipped either with a septum for
      conventional HS analysis or with one of four HS-SPME fibers [100 microm
      polydimethylsiloxane (PDMS), 85 microm carboxen (CAR)/PDMS, 75 microm CAR/PDMS,
      and 65 pm PDMS/divinylbenzene (DVB)]. The wheat was heated at 45 degrees C for 20
      min. In conventional HS analysis, a gaseous aliquot (80 pL) was taken from the HS
      and injected into the GC instrument. In the HS-SPME procedure, the fiber was
      removed from the HS and exposed in the heated injection port of the GC
      instrument. In all cases, PH3 was determined under the same chromatographic
      conditions with a GC pulsed flame photometric detector. In a comparison of the
      efficacy of the fibers, the bipolar fibers (CAR/PDMS and PDMS/DVB) contained more
      PH3 than the aliquot in the conventional HS analysis; larger size bipolar fibers
      extracted PH3 more efficiently than smaller fibers (e.g., 85 > 75 > 65 microm).
      The nonpolar fiber (PDMS) contained no PH3. Four fortification levels of PH3 on
      wheat were tested: 0.01, 0.05, 0.1, and 0.3 microg/g. The response of each
      bipolar fiber increased with the fortification levels, but the conventional HS
      analysis detected no fumigant at the lowest fortification level of 0.01 mg/g.
      Under the conditions of the validation study, the LOD was in the range of 0.005
      0.01 ng PH3/g wheat.

PMID- 22649945
TI  - Impact of the analytical blank in the uncertainty evaluation of the copper
      content in waters by flame atomic absorption spectrometry.
AB  - Chemical analysts use analytical blanks in their analyses, but seldom is this
      source of uncertainty evaluated. Generally, there is great confusion. Although
      the numerical value of the blank, in some situations, can be negligible, its
      source of uncertainty cannot be. This article discusses the uncertainty
      contribution of the analytical blank using a numerical example of the copper
      content in waters by flame atomic absorption spectrometry. The results indicate
      that the uncertainties of the analytical blank can contribute up to 50% when the
      blank sample is considered in this analysis, confirming its high impact. This
      effect can be primarily observed where the analyte concentration approaches the
      lower range of the analytical curve. Even so, the blank is not always computed.
      Therefore, the relevance of the analytical blank can be confirmed by uncertainty
      evaluation.

PMID- 22649944
TI  - Simultaneous determination of aminopyralid, clopyralid, and picloram residues in
      vegetables and fruits using ultra-performance liquid chromatography/tandem mass
      spectrometry.
AB  - A sensitive and effective method for the simultaneous quantitative determination
      of aminopyralid, clopyralid, and picloram in vegetables (eggplant, cucumber, and
      tomato) and fruits (apple and grape) was developed and validated using ultra
      performance LC coupled with MS/MS. The three herbicides were successfully
      separated and independently confirmed in a single run. Different extraction and
      cleanup methods were used to optimize the pretreatment processes of the residue
      analysis method. The final method is straightforward and involves extraction with
      1% formic acid-acetonitrile, and no complicated cleanup process is needed.
      Determination of the compounds was achieved within 3.0 min. Respective average
      recoveries using this method at four concentration levels (0.05, 0.1, 0.5, and
      1.0 mg/kg) ranged from 66.5 to 109.4%, with RSDs in the range of 1.1-19.7% (n =
      5) for all analytes. The LODs were below 0.010 mg/kg, and the LOQs did not exceed
      0.036 mg/kg, which were lower than the maximum residue limits (MRLs) of 0.5-5.0
      mg/kg clopyralid in vegetables and fruits samples, as established by the European
      Union. This study provides a theoretical basis for China to develop MRLs and an
      analytical method for aminopyralid, clopyralid, and picloram in vegetables and
      fruits.

PMID- 22649946
TI  - A quantitative method for residues of macrolide antibiotics in porcine kidney by
      liquid chromatography/tandem mass spectrometry.
AB  - An LC/MS/MS-based multiresidue quantitative method was developed for the
      macrolides erythromycin A, neospiramycin I, oleandomycin, spiramycin I,
      tilmicosin, and tylosin A in porcine kidney tissues. The Canadian Food Inspection
      Agency (CFIA) had as part of its analytical scope an LC/UV method for
      quantification of residues of two macrolide antibiotics, tilmicosin and tylosin
      A, in the kidney, liver, and muscle of cattle, swine, and poultry. The method
      could not reliably detect concentrations below 10 microg/kg. To increase the
      scope of the CFIA's analytical capabilities, a sensitive multiresidue
      quantitative method for macrolide residues in food animal tissues was required.
      Porcine kidney samples were extracted with acetonitrile and alkaline buffer and
      cleaned-up using silica-based C18 SPE cartridges. Sample extracts were analyzed
      using LC/MS/MS with positive electrospray ionization. Fitness for purpose was
      verified in a single-laboratory validation study using a second analyst. The
      working analytical range was 5 to 50 microg/kg. LOD and LOQ were 0.5 to 0.6
      microg/kg and 1.5 to 3.0 microg/kg, respectively. Limits of identification were
      0.5 to 2.0 microg/kg. Relative intermediate precisions were 8 to 17%. Average
      absolute recoveries were 68 to 76%.

PMID- 22649947
TI  - Top HIS vendors by 2011 revenue.

PMID- 22649949
TI  - EHR success all in the details.

PMID- 22649948
TI  - Shopping spree. The price of I.T. progress?

PMID- 22649950
TI  - The virtues of virtualization.

PMID- 22649951
TI  - Burning ring of data.

PMID- 22649952
TI  - The role of bladder neck preservation during radical prostatectomy: clinical and
      urodynamic study.
AB  - AIMS: Bladder neck preservation has caused an increase in urinary continence
      following radical prostatectomy, and has given rise to much controversy. We have
      reviewed our clinical and urodynamic experience collected since 1995 in patients
      subjected to radical prostatectomy with bladder neck preservation. MATERIALS AND
      METHODS: 180 patients were followed postoperatively using a pad test, an
      incontinence questionnaire and PSA dosage. In 66 early continent patients, test
      of maximum urethral closing pressure, functional length and active urethral
      continence were carried out, together with Valsalva leak point pressure tests and
      a pressure/flow study. The obtained data were then analysed. RESULTS: Urinary
      continence was achieved in 132/180 men (73%) already two weeks after operation.
      Three months, six months and one year later the continence rate was 89%, 95.5%
      and 97.7% (176/180) respectively. As far as the urodynamic parameters of the 66
      patients fully tested are concerned, all showed high results. The active urethral
      continence capacity exceeded 200 cm/water, and the Valsalva leak point pressure
      equalled or exceeded 150 cm/water. CONCLUSIONS: Following an accurate dissection
      of the distal urethra, bladder neck preservation guarantees early recovery of
      continence, as confirmed by local urodynamic figures, and restores functional
      integration of both the urethral sphincteric-smooth proximal and distal striated
      units.

PMID- 22649953
TI  - Stem cell markers aldehyde dehydrogenase type 1 and nestin expressions in renal
      cell cancer.
AB  - OBJECTIVES: To identify stem cell markers aldehyde dehydrogenase type 1 (ALDH-1)
      and nestin expression in renal cell carcinoma (RCC). MATERIALS AND METHODS: 95
      RCC patients who had radical or partial nephrectomy were included in this study.
      Normal renal tissue samples of the same patients were designated as the control
      group. Paraffin blocks of RCC patients were studied immunohistochemically.
      Expressions were analyzed semiquantitively. Relation of tumor grade and stage
      with these expressions was determined. Results were calculated with Mann Whitney
      U and Kruskal Wallis tests. RESULTS: There were 55 male (57.8%) and 40 (42.2%)
      female patients in the study. Age and sex of the patients were not correlated
      with their antibody expressions (p > 0.05). ALDH-1 and nestin expression was
      higher in cancer tissues than normal tissues (p < 0.05). Nestin expression in
      renal cencer tissue was inversely related with tumor stage (p < 0.05) but there
      was no relation with Fuhrman grade. ALDH-1 expression was correlated with tumor
      grade (p < 0.05) but not with tumor stage (p > 0.05). CONCLUSIONS: ALDH-land
      nestin expression have a role in RCC pathophysiology. There is a need to perform
      more studies about stem cell markers in RCC with more patients and in these
      future studies lymph node metastasis, distant organ metastasis and survival rates
      should be included.

PMID- 22649954
TI  - Paediatric balanitis xerotica obliterans: an 8-year experience.
AB  - OBJECTIVE: Balanitis Xerotica Obliterans (BXO) is rarely described in the
      paediatric population. We report our 8-year experience, at Harold Wood Hospital,
      with BXO in circumcised boys. MATERIALS AND METHODS: Pathological tissue
      diagnoses of BXO from 1997 to 2005 were extracted from our histopathology
      database. Patient records were reviewed and demographic features, clinical
      presentation, referral history, operative procedure(s) and postoperative course
      were recorded. RESULTS: A total of 40 patients had a confirmed tissue diagnosis
      of BXO. Mean patient age was 9.6 years. The most common referral diagnoses were
      phimosis (70%), balanitis (25%) and only 2 patients (5%) had a referral diagnosis
      of BXO. 35 (87%) underwent curative circumcision and had no recurrence at a
      median follow-up of 13.5 months. A total of 5 patients (15%) had BXO involvement
      of the meatus and underwent circumcision combined with meatotomy or meatoplasty.
      No patients required extensive plastic operations of the penis. CONCLUSIONS: The
      incidence of BXO in paediatric age group may be higher than previously reported.
      Early recognition of this condition is important because of the associated
      urethral stricture formation. Hence, we recommend that all circumcision specimens
      are sent for histopathological analysis (especially in areas where circumcision
      is widely practiced for ritual and religious reason) and patients should be
      followed up appropriately.

PMID- 22649955
TI  - The prognostic role of preoperative chromogranin A expression in prostate cancer
      after radical prostatectomy.
AB  - PURPOSES: The aim was to analyze the prognostic role of preoperative chromogranin
      A CgA) as a marker of poor prognosis and recurrence after radical prostatectomy
      (RP) and to find a correlation with the other well known prognostic variables.
      MATERIALS AND METHODS: This study comprises 306 patients with prostate cancer
      prospectively recruited who underwent RP from between 2000 and 2005. A blood
      sample for the determination of serum preoperative CgA value was obtained in all
      cases. Spearman correlation test was used to compare CgA to other variables,
      Kruskal-Wallis test to analyze CgA differences among > or = 3 groups (PSA, GS,
      Stage), Mann-Whitney test for 2 grouping variables. Survival analysis was
      estimated by Kaplan-Meier method, log-rank test to estimate differences among the
      analyzed variables. RESULTS: Median CgA level was 68 ng/ml. Correlation between
      age and CgA levels was positive and statistically significant (p < 0.001).
      Patient were divided in 2 groups based on median age.The difference was
      statistically significant (p = 0.002). Comparison of CgA among patients grouped
      according to other variables and patient stratified on normal (123 ng/ml) and cut
      off value (68 ng/ml) of CgA did not achieve significant risk stratification.
      CONCLUSION: Studies on a possible prognostic role of CgA have provided
      conflicting results. In our series we found a significant positive correlation
      between CgA and age, but no significant statistical correlation with other
      available variables analyzed.

PMID- 22649956
TI  - Does transrectal color Doppler ultrasound improve the diagnosis of prostate
      cancer?
AB  - OBJECTIVE: To prospectively evaluate whether TRUS guided biopsy associated with
      Color Doppler (CD) imaging improves the detection of PCa. MATERIAL AND METHODS:
      From January 2008 to December 2010, 144 subjects, with an increased PSA value or
      with a suspect digital rectal examination, were enrolled. Transrectal grey-scale
      Ultrasound (US) and CD examination were performed in all patients. CD US was
      considered positive or negative on the basis of the presence or absence of
      vascular abnormality. Prostate biopsy was performed immediately after grey-scale
      and Doppler evaluation, with a mean of 10 core-biopsy for each patient as well as
      a selective biopsy of all US abnormal areas (hypoechoic lesion or CD abnormality
      areas). RESULTS: PCa has been detected in 71 (49.3%) patients. 58 of the 71
      patients had a hypoechoic area at US scan and 27 had a CD abnormality. The PSA
      value was < 4 ng/ml in 11 patients (Group 1), in 63 patients PSA ranged between 4
      and 10 ng/ml (Group 2) and in 70 patients PSA was greater than 10 ng/ml (Group
      3). The detection rate was 36.7, 36.5 and 62.8% respectively. In Group 1 we
      detected 5 hypoechoic areas and 4 CD abnormal areas. Moreover 6 of 11 patients
      had a positive DRE. In the Group 2, 20 patients were positive to DRE; we
      visualized 21 hypoechoic areas and 7 CD abnormality. In the Group 3, 38 patients
      had a positive DRE, with 32 hypoechoic areas and 16 CD abnormalities found. We
      obtained 1537 total bioptic cores, 1440 randomly from peripheral gland, 70 from
      hypoechoic areas and 27 from abnormal CD flow areas. The detection rate was 17.1,
      65.7 and 22.2% respectively. CONCLUSION: CD US showed to be a complement to grey
      scale imaging of prostate unless insufficiently sensitive to replace the standard
      systematic 8-12 core random peripherally biopsy. Furthermore it should be
      associated routinely to TRUS to easily focus suspect areas.

PMID- 22649957
TI  - Comparative study of seminal parameters between samples collected in 1992 and
      samples collected in 2010.
AB  - OBJECTIVE: The aim of this study was to conduct a comparative study of semen
      quality in two large populations; one evaluated in 1992 and another in 2010, in
      order to evaluate any possible decline in male fertility due, at least in part,
      to environmental factors. MATERIAL AND METHODS: A total of 701 subjects in 1992
      (TOTAL group 1992) and a total of 626 subjects in 2010 (TOTAL group 2010) were
      enrolled in our Andrology Unit. Each group was subdivided into 3 subgroups:
      Subfertile, Pathology and Control. Standard semen analysis was performed using
      the Superimposed Image Analysis System, according to WHO guidelines 1987 (for
      TOTAL group 1992) and WHO guidelines 1999 (for TOTAL group 2010). RESULTS: The
      mean values of sperm number (concentration/ml as well as the total ejaculate) and
      progressive motility were significantly higher in TOTAL group 2010 than TOTAL
      group 1992. Atypical forms in TOTAL group 1992 semen samples were significantly
      lower than TOTAL group 2010. The mean age of TOTAL Group 2010 was significantly
      higher compared with TOTAL Group 1992. In particular, the mean age gap was more
      evident in Subfertile subjects. CONCLUSIONS: In conclusion, environmental factors
      have not determined a significant decline in seminal parameters in the past 18
      years.

PMID- 22649958
TI  - Does Ki-67 staining improve quantitative histology in preoperative prostate
      cancer staging?
AB  - To evaluate accuracy of Ki-67 expression on biopsy specimens in comparison with
      quantitative histology findings for preoperative prostate cancer (PCa) staging.
      From January 2008 to January 2010, 126 patients (median age 63 years) underwent
      radical retropubic prostatectomy; median PSA was 9.1 ng/mL; 98 and 28 patients
      had a clinical stage T1c and T2, respectively. The following variables of
      quantitative histology were evaluated as predictive of non organ-confined (OC)
      PCa: Gleason score > 6, TPC > 20%, GPC > 50%, cancer-positive cores > 2, presence
      of cancer-positive cores in both lateral margins and bilateral PCa. Value of Ki
      67% staining in all cancerous cores was calculated. Sixty (47.7%) patients had a
      non OC-PCa with positive nodes in 12 (20%) cases. The mean Ki-67 score was 4.4%:
      3.7% in OC-PCa and 5.6% in non-OC-PCa, respectively. Predictive positive value
      (PPV) of quantitative histology, Ki-67 (cut-off > 5%) and both parameters to
      predict a non-OC-PCa vs an OC-PCa was equal to 90%, 40% and 93.4%, vs 36.6%,
      78.8% and 78.8%, respectively. Ki-67 staining on biopsy specimens does not
      improve quantitative histology in predicting non-OC-PCa; moreover, the low
      expression of Ki-67, even in presence of advanced disease, decreases its
      prognostic value in predicting an OC-PCa.

PMID- 22649959
TI  - Development of a rapid food screener to assess the potential renal acid load of
      diet in renal stone formers (LAKE score).
AB  - AIM OF THE STUDY: The potential renal acid load of foods (PRAL) has been proposed
      as a causative factor of renal stone format ion in patients with calcium stones.
      Evaluation of the dietary PRAL seems to be advisable to evaluate the lithogenic
      potential of the diet of the individual patient. MATERIALS AND METHODS: On the
      basis of a dietary questionnaire administered to a sample of 75 renal stone
      formers living in the urban area of Milan (Northern Italy), we selected the most
      frequently reported foods for each of 11 categories: grains, meats, cured meats,
      eggs, cheeses, legumes, potatoes, vegetables, fruit and juices, milk and dairies
      and bread. The PRAL per 100 g of each food was calculated considering its mineral
      and protein composition, the mean intestinal absorption rate for each nutrient
      and the metabolism of sulfur-containing amino acids. The PRAL/100 g of each main
      food category was then calculated considering the frequency of the most
      represented (up to six) foods in the respective food group and the PRAL/100 g of
      each food. Subsequently the PRAL/100 g value for each main food category was
      adjusted for the standard serving size. Finally, according to the value of the
      adjusted PRAL value a score was assigned to each group of foods and named as LAKE
      (Load of Acid to Kidney Evaluation) score. RESULTS: The scores computed for
      grains, meats, cured meats, eggs, cheeses, legumes,potatoes, vegetables, fruit &
      juices, milk & dairies and bread were +2, +10, +6, +4, +10, -2, -10, -10, -10, +1
      and +1, respectively. Two report forms were designed to allow a rapid collection
      of data about the intake of each food group. Time requested for filling the forms
      and to compute scores ranges from 2 to 4 minutes (report forms can be requested
      to a.trinchieri@ospedale.lecco.it). CONCLUSION: LAKE score can be an useful and
      simple tool in order to evaluate the dietary PRAL and to suggest modifications to
      achieve its reduction for the prevention of calcium nephrolithiasis and other
      diseases.

PMID- 22649960
TI  - An innovative combined antero-retrograde approach for the resolution of the
      complete iatrogenic obliteration of ureteral ostium: a case report.
AB  - In selected cases of endoscopic surgery of bladder cancer, in order to reach an
      oncologic radicality, the resection of the ureteral ostium affected by the
      disease is required. Although infrequent, a possible complication of this
      manoeuvre is represented by the complete obliteration of theresected ostium.
      Literature suggests that the traditional "open" surgery and the latest
      "laparoscopic" surgery are effective in the resolution of this complication, in
      contrast with the techniques of endourological and uro-interventional radiology
      which, although minimally invasive, do not appear to be completely appropriate in
      the treatment of this condition. We believe that an innovative, minimally
      invasive anterograde trans-nephrostomic and retrograde endoscopic combined
      approach can be decisive in restoring complete patency of the neo-ostium.

PMID- 22649961
TI  - Amelanotic malignant melanoma of the penis. A case report and literature review.
AB  - Malignant melanoma (MM) of the penis represents an uncommon form of genitourinary
      malignancies, which account for about 1% of all cases of melanoma. Amelanotic
      malignant melanoma (AMM) lacks the pigmented elements, which is the hallmark of
      melanoma. This is a challenging diagnosis since confusion might be made with a
      variety of benign lesions, causing a delay in appropriate medical treatment.
      Taking into consideration that prognosis is the same for melanotic and amelanotic
      melanoma, early diagnosis is crucial. We describe a patient with amelanotic
      melanoma of the penis, treated with partial penectomy.

PMID- 22649963
TI  - Clinical perspectives on platelet function testing.

PMID- 22649962
TI  - Disorders of bladder depletion in a young man because of a prostatic cyst: a case
      report.
AB  - Symptomatic prostatic cysts presenting with recurrent urinary tract infections
      and urinary obstructive disorders in young men may be misdiagnosed as benign
      prostatic hyperplasia, urethral stenosis or neuropathic bladder. We report a case
      of a 28 year old young man with obstructive and irritative voiding disorders
      caused by a prostatic cyst, located in the anterior and left lateral lobe of the
      prostate gland. The cyst appeared to obstruct the bladder outlet by a "ball
      valve" mechanism. The prostatic cyst was incised and marsupialized by
      transurethral resection. At post-operative follow up we observed an increase in
      Qmax with no residual urine and negative urine culture. The patient showed no
      retrograde ejaculation nor erectile dysfunction.

PMID- 22649964
TI  - Digital imaging in hematology.

PMID- 22649965
TI  - The manual differential enters the digital age.

PMID- 22649966
TI  - The expanding role of PCR in research and medicine.

PMID- 22649969
TI  - Information technology: impacting pathology in the future...or not?

PMID- 22649967
TI  - How rapid is rapid?

PMID- 22649968
TI  - Progress report: why we still don't have a reliable gold standard for in vitro
      diagnostic genetic testing.

PMID- 22649970
TI  - "The pathology profession has evolved". A conversation with Richard Zarbo, MD.
      Interview by Joel Servais.

PMID- 22649971
TI  - The future in focus.

PMID- 22649972
TI  - Automated temperature monitoring systems: factors to consider.

PMID- 22649974
TI  - Quality control: more challenges for molecular diagnostics.

PMID- 22649973
TI  - "We can get much more information": a conversation with Emory Healthcare's
      Cynthia Channell.

PMID- 22649976
TI  - Don't forget clinical laboratories.

PMID- 22649975
TI  - Understanding legal and regulatory pressure points in lab transactions.

PMID- 22649978
TI  - Dan Edson and the American Proficiency Institute provide ways to assess the
      accuracy of lab tests.

PMID- 22649977
TI  - A reader's correction.

PMID- 22649979
TI  - Protect women's health.

PMID- 22649980
TI  - Slinking toward the bomb. How close is Iran to acquiring a nuclear weapon?

PMID- 22649981
TI  - The motherhood gap.

PMID- 22649982
TI  - Fire and water.

PMID- 22649983
TI  - Microbial mules.

PMID- 22649984
TI  - Thar she blows!

PMID- 22649986
TI  - Happy birthday, electron.

PMID- 22649985
TI  - Old neurons, new tricks.

PMID- 22649988
TI  - Primeval precipitation.

PMID- 22649987
TI  - The case of the traveling salesman.

PMID- 22649989
TI  - Lice don't lie.

PMID- 22649990
TI  - The scoop on eating dirt.

PMID- 22649991
TI  - Down with double data fees!

PMID- 22649993
TI  - Super supernovae.

PMID- 22649994
TI  - The human brain project.

PMID- 22649992
TI  - The ultimate social network.

PMID- 22649995
TI  - Fusion's missing pieces.

PMID- 22649996
TI  - Busy bee.

PMID- 22649997
TI  - Waiting to explode.

PMID- 22649998
TI  - The right way to get it wrong.

PMID- 22649999
TI  - Life is a shell game.

PMID- 22650000
TI  - Resistance fighter. Interview by Brendan Borrell.

PMID- 22650001
TI  - The science of righteousness.

PMID- 22650002
TI  - Water in, water out.

PMID- 22650003
TI  - Small dense LDL: risk factor for coronary artery disease (CAD) and its
      therapeutic modulation.
AB  - Pathogenesis of coronary artery disease (CAD) is multi-factorial and many risk
      factors are associated with development of CAD. LDL-C has been an important
      target for therapeutic interventions and has been extensively studied. But,
      various studies have indicated that estimation of LDL-C is not enough to assess
      the risk. Moreover, LDL particles vary in their content, density and size which
      have different physico-chemical properties. In this paper, the role of small
      dense (sd) LDL in risk assessment for CAD and its response to different
      therapeutic modalities available have been reviewed.

PMID- 22650004
TI  - Cordycepin induces apoptosis in human neuroblastoma SK-N-BE(2)-C and melanoma SK
      MEL-2 cells.
AB  - In this study, the effect of cordycepin (3'-deoxyadenosine), a major component of
      Cordyceps militaris, an ingredient of traditional Chinese medicine was
      investigated for the first time on apoptotsis in human neuroblastoma SK-N-BE(2)-C
      and melanoma SK-MEL-2 cells. Cordycepin significantly inhibited the proliferation
      of human neuroblastoma SK-N-BE(2)-C and human melanoma SK-MEL-2 cells with IC50
      values of 120 microM and 80 microM, respectively. Cordycepin treatment at 120
      microM and 80 microM, respectively, induced apoptosis in both cells and caused
      the increase of cell accumulation in a time-dependent manner at the apoptotic sub
      G1 phase, as evidenced by the flow cytometry (FCM) and annexin V-fluorescein
      isothiocyanate (FITC) analyses. Western blot analysis revealed the induction of
      active caspase-3 and poly(ADP-ribose)polymerase (PARP) cleavage by cordycepin
      treatment. These results suggest that cordycepin is a potential candidate for
      cancer therapy of neuroblastoma and melanoma.

PMID- 22650005
TI  - Inhibitory effect of antibodies against human chorionic gonadotropin on the
      growth of colorectal tumour cells.
AB  - Human chorionic gonadotropin (hCG) was initially believed to be secreted
      exclusively by the embryo with its primary function being "rescue" of the corpus
      luteum. However, recently it has been found that the hormone (or its individual
      subunits) is also secreted by many cancers and that in many cases secretion is
      associated with poor patient prognosis. In this study, we assessed the presence
      of hCG in colorectal cancer cells (CCL-253) and evaluated the anti-tumour effects
      of anti-hCG antibodies in vitro and in vivo. Anti-hCG antibodies were reactive
      with CCL-253, as revealed by confocal immunoflourescence microscopy; both cell
      surface and intracellular expression were observed. Western blot analysis showed
      that antibodies appeared to interact with several moieties, indicating a level of
      cross-reactivity. Anti-hCG antiserum specifically reduced the viability of tumor
      cells and the addition of complement increased in vitro anti-tumor effects. In
      nude mice implanted with CCL-253 cells, administration of anti-hCG antiserum
      caused a significant reduction in tumor volume; all treated animals survived,
      while mortality was observed in control animals. Results suggest that anti-hCG
      antibodies can mediate significant anti-tumor activity both in vitro and in vivo
      and lend support to the rationale of anti-hCG immunization in the therapy of
      gonadotropin- sensitive cancers.

PMID- 22650007
TI  - Pharmacophoric studies of in vitro inhibition of Plasmodium falciparum growth.
AB  - Malaria continues to be a scourge in India and the situation has been compounded
      by the emergence of resistant strains of Plasmodium falciparum which is the
      primary cause of fatality in this disease. Therefore, there is an urgent need to
      develop newer drugs. Molecular modeling and pharmacophoric determination have
      become predominant methods today in the design and synthesis of newer and more
      effective drugs. Many Plasmodium specific enzymes and proteins involved in
      crucial biochemical pathways have been identified and their structures have been
      determined by X-ray crystallography. These enzymes and proteins are excellent
      targets for newer antimalarial agents. Bisphosphonates have shown potent
      inhibitory activity against Plasmodium farneysl diphosphate synthase (FPPS)
      enzyme, which is vital to the protein prenylation pathway of the organism. In
      this study, a set of 26 bisphosphonate inhibitors, synthesized by Oldfield et al
      [J Med Chem (2008) 51, 7827-7833] were subjected to rigorous 3D-QSAR studies
      using the PHASE computational package. In vitro Plasmodium growth inhibition
      rather than direct enzyme inhibition was considered in the study for a more
      realistic approach. Good statistical correlations were obtained for the
      pharmacophoric model as revealed by the regression values, indicating good
      stability of the model. Three hydrogen bond acceptors and a hydrogen bond donor
      defined the pharmacophore from the present study. This pharmacophore, AAAD (A =
      Hydrogen bond acceptor and D = Hydrogen bond donor) was put through a search-run
      for matching structures from the SPECS database yielding four matching
      structures, which could function as starting points for more novel and potent
      antimalarials.

PMID- 22650006
TI  - Relation of CuZnSOD activity with renal insufficiency in hypertensive diabetic
      patients.
AB  - Diabetes and renal insufficiency are interrelated metabolic disorders closely
      associated with redox homeostasis disturbances. The aim of this study was to
      compare the activity of copper zinc superoxide dismutase (CuZnSOD) in the
      erythrocytes of hypertensive diabetic patients with or without renal
      insufficiency with normal healthy control subjects. In both groups of diabetic
      patients, blood glucose level and the content of glycosylated hemoglobin (HbA1c)
      were higher than in the control group. However, CuZnSOD activity was
      significantly higher than control only in hypertensive diabetic patients with
      renal insufficiency. Our results suggest that disturbances in superoxide
      homeostasis do correlate with long-term complication in diabetes, i.e. diabetic
      renal insufficiency and hypertension.

PMID- 22650008
TI  - Purification and some properties of rose (Fructus cynosbati) hips invertase.
AB  - Invertase was purified from rose (Fructus cynosbati) hips by ammonium sulfate
      fractionation and hydroxyapatite column chromatography. The enzyme was obtained
      with a yield of 4.25% and about 10.48-fold purification and had a specific
      activity of 8.59 U/mg protein. The molecular mass of invertase was estimated to
      be 66.51 kDa by PAGE and 34 kDa by SDS-PAGE, indicating that the native enzyme
      was a homodimer. The enzyme was a glycoprotein and contained 5.86% carbohydrate.
      The K(m) for sucrose was 14.55 mM and the optimum pH and temperature of the
      enzyme were 4.5 and 40 degrees C, respectively. Sucrose was the most preferred
      substrate of the enzyme. The enzyme also hydrolyzed D(+) raffinose, D(+)
      trehalose and inulin (activity 39.88, 8.12 and 4.94%, respectively of that of
      sucrose), while D(+) lactose, cellobiose and D(+) maltose showed no effect on the
      enzyme. The substrate specificity was consistent with that for a beta
      fructofuranoside, which is the most popular type in the higher plants. The enzyme
      was completely inhibited by HgCl2, MnCl2, MnSO4, FeCl3, Pb(NO3)2, ammonium
      heptamolybdate, iodoacetamide and pyridoxine hydrochloride. It was also inhibited
      by Ba(NO3)2 (86.32%), NH4Cl (84.91%), MgCl2 (74.45%), urea (71.63%), I2 (69.64%),
      LiCl (64.99%), BaCl2 (50.30%), Mg(NO3)2 (49.90%), CrCl3 (31.90%) and CuSO4
      (21.45%) and but was activated by Tris (73.99%) and methionine (12.47%).

PMID- 22650009
TI  - Carbohydrate content and antioxidative potential of the seed of three edible
      indica rice (Oryza sativa L.) cultivars.
AB  - Rice (Oryza sativa L.) grains or seeds are known to lose much of their nutrient
      and antioxidant contents, following polishing. The current study was undertaken
      to evaluate and compare the carbohydrate content and antioxidant parameters in
      the unpolished and polished seeds of three edible indica rice cultivars, namely
      Swarna (SW), the most popular indica rice cultivar in India and aromatic or
      scented cultivars Gobindobhog (GB) and Pusa Basmati (PB). While both the sucrose
      and starch content was the maximum in PB seeds (both unpolished and polished),
      the amylose content was the highest in SW polished seeds. SW polished seeds were
      superior as compared to GB and PB cultivars in terms of total antioxidant
      capacity, DPPH radical scavenging and Fe(II) chelation potential, as well as the
      highest lipoxygenase (LOX) inhibition or H2O2 scavenging potential, probably due
      to the maximum accumulation of total phenolics and flavonoids, the two important
      antioxidants. The reducing power ability was, however, identical in both SW and
      GB polished seeds. The PB polished seeds were more potent in superoxide and
      hydroxyl scavenging, whereas GB in nitric oxide (NO) scavenging. The common
      observation noted after polishing of seeds was the reduction in the level of
      carbohydrates and antioxidant potential, though the extent of reduction varied in
      the three cultivars. The only exception was GB, where there was no alteration in
      NO scavenging potential even after polishing. Our study showed the better
      performance of SW polished seeds with respect to higher amylose content and
      majority of the tested parameters governing antioxidant capacity and radical
      scavenging potential, thus highlighting the greater dietary significance of SW
      over the other two cultivars.

PMID- 22650010
TI  - In vitro antioxidant activity of banana (Musa spp. ABB cv. Pisang Awak).
AB  - The methanolic extract of Musa ABB cv Pisang Awak was investigated for the
      polyphenolic contents and antioxidant activity. The total phenol and flavonoid
      contents of the fruit extract were found to be 120 mg gallic acid equivalents
      (GAE) and 440 mg quercetin equivalents (QE)/100 g of sample dry weight,
      respectively. The antioxidant activity of the Pisang Awak methanol extract (PAME)
      (20-500 microg/ml) was determined using 1,1-diphenyl-2-picryl hydrazyl (DPPH)
      radical scavenging activity, reducing capacity, 2-2'-azinobis-3
      ethylbenzothiozoline-6-sulfonic acid (ABTS) radical cation decolourization and
      hydroxyl radical scavenging capacity (OH*). The EC50 values of DPPH, ABTS and OH*
      activities of the PAME and butylated hydroxy toluene (BHT) were found to be 65
      and 9 microg/ml, 29 and 6 microg/ml, 36 and 42 microg/ml respectively. The
      reducing capacity increased with increasing concentration (31.5-1000 mg/ml) of
      the fruit extract and the activity was comparable with the standard BHT. The high
      performance thin layer chromatography (HPTLC) analysis of the extract revealed
      the presence of polyphenols. The strong and positive correlations were obtained
      between total phenol/flavonoid contents (R2 = 0.693-1.0) and free radical
      scavenging ability was attributed to the polyphenols as the major antioxidants.

PMID- 22650011
TI  - Effect of sodium fluoride and magnesium chloride on different hydroxyproline
      fractions in rat liver.
AB  - Sodium fluoride (NaF) is used for prevention of caries in the form of fluoridated
      drinking water, fluoride tablets etc. In the present study, the effect of NaF
      induced alterations in hydroxyproline (Hyp) and collagen was investigated in rat
      liver. The effect of pretreatment with MgCl2 on NaF-induced changes in liver Hyp
      and collagen was also studied. The NaF treatment at 5, 10 and 20 mg/kg body wt
      (reported LD50 of NaF being 24 mg/kg body wt through intraperitoneal route)
      caused a significant decrease in free Hyp (P < 0.05), when compared to control
      rats. The rats treated with 20 mg/kg body wt of NaF showed a significant increase
      in protein-bound Hyp (P < 0.001), as compared to control group, while of NaF
      treatment at 5 and 10 mg/kg body wt caused no significant change in protein-bound
      Hyp. All the doses of NaF had no significant effect on peptide-bound and total
      Hyp and total collagen. Treatment of with MgCl2 alone (30 mg/kg body wt) or with
      NaF (10 mg/kg body wt) caused a significant decrease in free Hyp (P < 0.05).
      MgCl2 alone and with NaF caused a significant increase (P < 0.05) in total
      collagen content. Thus, the present study demonstrated that NaF had no
      significant effect on total Hyp and collagen, indicating that its use in various
      products may not interfere with the liver collagen.

PMID- 22650012
TI  - Meeting report.

PMID- 22650013
TI  - Good news and not-so-good news.

PMID- 22650014
TI  - Compensation for nonprofit health care board members: the right path or a
      minefield?

PMID- 22650015
TI  - The effects of market structure and payment rate on the entry of private health
      plans into the Medicare market.
AB  - Private insurance firms participating in Medicare can offer up to three principal
      plan types: coordinated care plans (CCPs), prescription drug plans (PDPs), and
      private fee-for-service (PFFS) plans. Firms can make entry and marketing
      decisions separately across plan types and geographic regions. In this study, we
      estimate firm-level models of Medicare private plan entry using data from the
      years 2007 to 2009. Our models include a measure of market structure and
      separately identify CCP, PDP, and PFFS entry. We find evidence that entry
      barriers associated with CCP market concentration affect all three product types.
      We also find evidence of cross-product competition and common cost or demand
      factors that make entry with certain product combinations more likely. We predict
      that the market presence of CCPs and PFFS plans will decrease and that of PDPs
      will increase in response to payment reductions included in the new health reform
      law.

PMID- 22650017
TI  - Public and private health insurance premiums: how do they affect the health
      insurance status of low-income childless adults?
AB  - The Patient Protection and Affordable Care Act (ACA) will substantially increase
      public health insurance eligibility and alter the costs of insurance coverage.
      Using Current Population Survey (CPS) data from the period 2000-2008, we examine
      the effects of public and private health insurance premiums on the insurance
      status of low-income childless adults, a population substantially affected by the
      ACA. Results show higher public premiums to be associated with a decrease in the
      probability of having public insurance and an increase in the probability of
      being uninsured, while increased private premiums decrease the probability of
      having private insurance. Eligibility for premium assistance programs and
      increased subsidy levels are associated with lower rates of uninsurance. The
      magnitudes of the effects are quite modest and provide important implications for
      insurance expansions for childless adults under the ACA.

PMID- 22650016
TI  - The impact of maternity length-of-stay mandates on the labor market and insurance
      coverage.
AB  - To understand the effects of insurance regulation on the labor market and
      insurance coverage, this study uses a difference-in-difference-in-differences
      analysis to compare five states that passed minimum maternity length-of-stay laws
      with states that waited until after a federal law was passed. On average, we do
      not find statistically significant effects on labor market outcomes such as hours
      of work and wages. However, we find that employees of small firms in states with
      maternity length-of-stay mandates experienced a 6.2-percentage-point decline in
      the likelihood of having employer-sponsored insurance. Implementation of federal
      health reform that requires minimum benefit standards should consider the
      implications for firms of differing sizes.

PMID- 22650018
TI  - The relationship of hospital quality and cost per case in Hawaii.
AB  - One of the leading questions of our time is whether high-quality care leads to
      lower health care costs. Using data from Hawaii hospitals, this paper addresses
      the relationship of overall cost per case to a composite measure of the quality
      of inpatient care and a 30-day readmission rate. We found that low-cost hospitals
      tend to have the highest quality but the worst readmission performance. Change in
      quality and change in cost were also negatively correlated, but not statistically
      significant. We conclude that high-quality hospital care does not have to cost
      more, but that the dynamics of the readmission rate differ substantially from
      other quality dimensions.

PMID- 22650019
TI  - [Cloning of splicing variants of alpha1,3-galactosyltransferase cDNA of Chinese
      Banna Minipig inbred line and its expression in human cells].
AB  - OBJECTIVE: To study the transfection and expression of the splicing variants of
      alpha1, 3-galactosyltransferase cDNA of Chinese Banna Minipig Inbred Line (BMI)
      in human A549 cells. METHODS: Full length of alpha1,3-GT gene cDNA was amplified
      by RT-PCR from total RNA of BMI liver tissue and cloned into T-A cloning vector.
      Two different splicing variants of BMI alpha1,3-GT cDNA were confirmed by
      sequencing 15 positive clones and inserted respectively into pEGFP-N1 to
      construct eukaryotic expression vectors pN-GT1 and pN-GT2. The vectors were
      transfected into human lung adenocacinoma A549 cells and the expression of
      alpha1,3-GT gene was detected by RT-PCR. The expression of the a-Gal epitopes on
      transfected cells was confirmed under fluorescent microscope and by flow
      cytometry using FITC-BS-IB4 lectin. The binding of IgM and complement C3 in human
      serum to a-Gal on transfected cells were measured by flow cytometry using FITC
      anti-IgM and FITC-anti-C3. RESULTS: There was no other splicing variants of
      alpha1,3-GT cDNA found in BMI except GT1 and GT2, which were 1116 bp and 1080 bp
      in length respectively, the latter lacks exon 5. The expression of BMI alpha1,3
      GT mRNA and the synthesis of a-Gal on A549 cells transfected with either pN-GT1
      or pN-GT2 were detected, and the binding of IgM nature antibodies and complements
      C3 in human serum on transfected A549 cells were observed. The expression level
      of alpha-Gal and the deposits of IgM and C3 on transffected cells showed no
      significant difference between pN-GT1 and pN-GT2. CONCLUSION: The splicing
      variants of alpha1,3-GT cDNA of BMI could express in human cells, which provide
      the basis for genetic manipulation of the alpha1,3-GT of BMI for future
      xenotransplantation studies.

PMID- 22650020
TI  - [Establishment of a cisplatin-resistant human cervical cancer cell line].
AB  - OBJECTIVE: To establish a cisplatin (cDDP)-resistant human cervical cancer cell
      line named SiHa/cDDP and researched its biological characteristics. METHODS: The
      development of cDDP resistance in SiHa cell line was induced by continuously
      stepwise exposure of the cells to cDDP. Cell growth curve, doubling time and
      resistance index (RI) were evaluated by MTT analysis. The expression of P-gp, GST
      pi, Topo I were assessed with immunocytochemical method. RESULTS: SiHa/cDDP cell
      line was successfully established which had stable growth, subculture, frozen
      reservation and resuscitation in the concentration of 2 microg/ml cDDP, doubling
      time was (45.82 +/- 3.69) h and RI to cDDP was 16.131. It also showed different
      degrees of cross-resistance to several anticancer drugs. As compared to parental
      SiHa, SiHa/cDDP had over-expression in P-gp and GST-pi (P < 0.01), but Topo I
      showed no statistically significant differences. CONCLUSION: We successfully
      established the cDDP-resistant human cervical cancer cell line SiHa/cDDP, which
      may provide ideal experimental model for research of human cervical carcinoma.

PMID- 22650022
TI  - [Effect of nesprin-1 in the differentiation of mouse embryonic stem cells into
      cardiomyocytes].
AB  - OBJECTIVE: To investigate the role of nesprin-1 in mouse embryonic stem cells
      differentiation into cardiomyocyte. METHODS: Hanging drop-suspension-adherence
      method was applied for the differentiation of mouse embryonic stem cells into
      cardiomyocytes under the inducing of salvia miltorrhiza and 5-azacytidine.
      Changes in nesprin-1 gene expression were detected by using Western blotting and
      immunofluorescent assay. RNA interference was used to reduce nesprin-1 protein
      levels to further investigate the importance of nesprin-1 in mouse embryonic stem
      cells differentiation, group I (target sequence AAAGCCAAGCACGCAACTA), group II
      (target sequence GGGAACCAACAGTGAGATT), group III (target sequence
      ACCAGGACATTGCGTACTA), and group IV (control group). RESULTS: The nesprin-1
      isoform profile was altered in mouse embryonic stem cells differentiation. The
      rates of differentiation of the four groups were (17.78 +/- 1.92)%, (36.67 +/-
      3.34)%, (44.42 +/- 5.08)%, (77.78 +/- 1.92)%; The rate of differentiation of
      group IV was higher than RNAi groups and the difference was significant (P <
      0.05). In addition, compared with the control group, myosin in RNAi groups were
      dramatically reduced. CONCLUSION: Nesprin-1 played important roles in mouse
      embryonic stem cells differentiation into cardiomyocyte. Nesprin-1 isoforms might
      perform different functions in the process of mouse embryonic stem cells
      differentiation.

PMID- 22650021
TI  - [The expressions and correlation of bcl-2 and Beclin-1 in pancreatic cancer].
AB  - OBJECTIVE: To investigate the expressions of Bcl-2 and Beclin-1 in pancreatic
      cancer and analyze the correlation between them. METHODS: The pancreatic tissue
      samples were collected from each 6 cases of pancreatic cancer, pancreatic
      exocrine benign tumor, chronic pancreatitis and normal pancreas and marked as
      group A, group B, group C and group D, respectively. The mRNA expression levels
      of Bcl-2 and Beclin-1 were detected by real-time fluorescence quantitative PCR
      and the protein expression levels of Bcl-2 and Beclin-1 were detected through
      immunohistochemistry. RESULTS: The expression levels of Bcl-2 mRNA and protein,
      were the lowest in group D and the highest in group A (P < 0.05). The expression
      levels of Beclin-1 mRNA and protein in group A were significantly lower than
      those in group B and group D (P < 0.05). However, the expression levels of Beclin
      1 between group A and group C were not significantly different (P > 0.05). The
      correlation coefficient between Bcl-2 and Beclin-1 protein expression in
      pancreatic cancer is--0.827 (P = 0. 042). CONCLUSION: Compared with normal
      pancreatic tissue, pancreatic cancer had Bcl-2 expression upregulated and Beclin
      1 expression downregulated. The increased anti-apoptotic effect of Bcl-2 and the
      decreased autophagic effect of Beclin-1 may collaboratively contribute to the
      occurrence of pancreatic cancer.

PMID- 22650023
TI  - [PP2A is involved in the inhibitory effect of progesterone on proliferation of
      mouse endometrial epithelial cells].
AB  - OBJECTIVE: To study the effect of protein phosphatase 2A (PP2A) in the negative
      regulation of progesterone on the proliferation of mouse endometrial epithelial
      cells (EECs). METHODS: Mouse EECs were isolated and cultured in vitro, which were
      divided into four groups when they grown to confluence: control group (P4) was
      treated with 1 micromol/L progesterone only, group A, B and C were treated
      respectively with 1 micromol/L progesterone and different concentrations of
      okadaic acid (5 nmol/L, 10 nmol/L and 20 nmol/L). After 24 h, the numbers of
      cells in different phases of the cell cycle were counted with flow cytometry.
      RESULTS: The effect of OA on mouse EECs was concentration-dependent. Compared
      with control group of P4, the change of cell cycle procession in group A was not
      obvious. Lower proportion of cells in G1 and G2/M phase and higher proportion of
      cells in S phase in group B, higher proportion of cells in G1 and S phase and
      lower proportion of cells in G2/M phase in group C were observed. CONCLUSION:
      Adequate dose OA inhibiting PP2A could release the inhibitory effect of
      progesterone on proliferation of mouse EECs obviously, this suggested that PP2A
      was involved in the inhibitory effect of progesterone on proliferation of EECs by
      influencing the process of cell cycle.

PMID- 22650024
TI  - [Effects of sodium aescinate on the apoptosis-related genes in lung injury
      induced by intestinal ischemia reperfusion in rats].
AB  - OBJECTIVE: To investigate the relationship between apoptosis-related genes and
      lung injury induced by intestinal ischemia reperfusion and to explore the effects
      and its possible mechanism of sodium aescinate. METHODS: Rat model of intestinal
      I/R injury was established with clamping of the superior mesenteric artery for 60
      min and then clamping was relieved for 60 min. Twenty-four SD rats were randomly
      divided into three groups with eight rats in each: sham group, intestinal
      ischemia/reperfusion group (I/R group) and sodium aescinate group (SA + I/R
      group). Lung wet/dry weight ratio, lung coefficient and Superoxide dismutase
      (SOD), malondialdehyde (MDA) in plasma and lung tissue were measured, as well as
      the expression levels of Bcl-2 and Bax proteins in lung tissue were examined
      using immunohistochemical method. RESULTS: Compared with sham group, lung wet/dry
      weight ratio, lung coefficient and MDA in plasma and lung tissue were
      significantly increased, and while the activity of SOD in plasma and lung tissue
      were decreased significantly in I/R group. At the same time, the protein
      expression level of Bcl-2 and Bax were significantly increased. But Bax protein
      expression was much greater than that of Bcl-2, the ratio of Bcl-2 to Bax was
      decreased significantly in I/R group than that in sham group. Compared with I/R
      group, lung wet/dry weight ratio, lung coefficient and MDA in plasma and lung
      tissue were significantly decreased, and while the activity of SOD in serum and
      lung tissue were significantly increased in SA + I/R group. At the same time, Bax
      protein expression was significantly decreased, both Bcl-2 protein expression and
      the ratio of Bcl-2 to Bax were significantly increased in SA + I/R group than
      that in I/R group. CONCLUSION: Lung injury induced by intestinal ischemia
      reperfusion is correlated with abnormal expression levels of Bcl-2 and Bax
      protein which is caused by oxidative injury. Sodium aescinate can protect the
      lung injury induced by intestinal ischemia/reperfusion (I/R), which may be
      mediated by inhibiting lipid peroxidation, upregulating Bcl-2 gene protein
      expression, improving the ratio of Bcl-2/ Bax to inhibit lung apoptosis.

PMID- 22650025
TI  - [Effects of Marsdenia tenacissima extract on proliferation and apoptosis of
      hematologic neoplasm cell line cells].
AB  - OBJECTIVE: To investigate the effects of the extract from Marsdensia tenacissima
      on proliferation and apoptosis of human hematologic neoplasm cell line cells.
      METHODS: Raji, NB4 and K562 cells were treated in vitro with different
      concentrations of the extract from Marsdensia tenacissima, including different
      ethanol elution components and C21 steroidal saponin monomer compounds, for
      different periods. Tumor cell proliferation was measured by MTT colorimetric
      assay and its apoptosis was determined by the flow cytometry (FCM). RESULTS:
      Firstly, with higher concentrations, 100 microg/mL and 200 microg/mL, 70% ethanol
      eluate from Marsdensia tenacissima inhibited the proliferation of Raji, NB4 and
      K562 cells significantly, in a dose and time dependent manner, compared with 30%
      and 50% ethanol elution components from Marsdensia tenacissima (P < 0.05).
      Secondly, four C21 steroidal saponin monomer compounds, tenacissosides B,C,I and
      marsdenoside K, also inhibited the proliferation of Raji, NB4 and K562 cells in
      vitro significantly, in a dose and time dependent manner, compared with that of
      control group (P < 0.05). Among them, tenacissoside C showed the strongest
      inhibition effects on proliferation of these cells under all experimental
      conditions compared with the other three C21 steroidal saponin monomer compounds
      (P < 0.05). Furthermor, the IC50 of tenacissosides C on proliferation of Raji,
      NB4 and K562 cells were 64.1 micromol/L, 70.4 micromol/L and 105.8 micromol/L,
      respectively. Finally, after Raji, NB4 and K562 cells were treated with 98.4
      micromol/L tenacissoside C for 24 h and 48 h, the early apoptosis rates and late
      apoptosis rates of these tumor cells increased markedly, compared with the
      control group (P < 0.05). CONCLUSION: The extract from Marsdensia tenacissima,
      including different ethanol elution components and C21 steroidal saponin monomer
      compounds, may inhibit the proliferation of some human hematologic neoplasm cell
      line cells and induce these tumor cells apoptosis in vitro, especially
      tenacissoside C, one of the C21 steroidal saponin monomer compounds, showed the
      strongest effects on proliferation of these tumor cells when compared with other
      ones, with the strongest inhibition activities on human Burkitt's lymphoma cell
      line Raji cells.

PMID- 22650026
TI  - [CCR1 expression on immune cells in orbital tissue of patients with thyroid
      associated ophthalmopathy].
AB  - OBJECTIVE: To investigate the expression of CC chemokine receptor 1(CCR1) on the
      immune cells in orbital tissue of patients with thyroid associated
      ophthalmopathy(TAO). METHODS: The tissue samples of orbital tissue were collected
      from 25 cases of TAO patient and 10 normal control subjects, and the expression
      of CCR1 in the immune cells was studied by SP immunohistochemistry. The
      correlation between CCR1 and clinical activity scores (GAS) was analyzed.
      RESULTS: The expression of CCR1 on immune cells was positive, in orbital tissue
      of patients with TAO, and the positive rate was 84%, while it was negative or low
      positive in normal control subjects. The difference between them was significant
      (P < 0.05). In addition, the expression of CCR1 on the immune cells of orbital
      tissue with TAO had significant correlation with CAS (P < 0.05). CONCLUSION: The
      expression of chemokine receptor CCR1 on the immune cells in orbital tissue of
      TAO patients is higher than that of normal subjects. CCR1 may play a role in the
      pathogenesis of TAO.

PMID- 22650027
TI  - [Effect of low-intensity pulsed ultrasound on periodontitis in Beagle dogs].
AB  - OBJECTIVE: To investigate the effect of low intensity pulsed ultrasound (LIPUS)
      on periodontitis in Beagle dogs. METHODS: The animal model of chronic
      periodontitis was established with elastic ligature-induced alveolar bone defect
      in Beagle dogs. LIPUS with different intensity (50 mW/cm2, 100 mW/cm2) pulse wave
      and 50 mW/cm2 continuous wave, 1.5 MHz of frequency, 200 micros of pulse width
      modulated signal, and 1 kHz of repetition rate were applied to the dogs for 8
      weeks (once a day and 20 minutes every time). The periodontal clinical
      examinations and histological biopsy were performed. RESULTS: With increased
      exposure to LIPUS, gum tissue swelling of the dogs was reduced. The plaque index
      (PLI), gingival index (GI), pocket depth (PD) of the treatment groups were lower
      than the control groups (P < 0.05). No significant gingival recession, attachment
      loss or furcation was found. The histological examination revealed that there was
      no obvious gingival hyperplasia in epithelial tissues, but there were significant
      activities in relation to collagen formation, decrease of bone resorption, and
      generation of active osteoblasts. CONCLUSION: LIPUS may help repair periodontal
      tissues and should be considered in guided tissue regeneration (GTR).

PMID- 22650028
TI  - [The role of oxidative stress in the pathogenesis of polycystic ovary syndrome].
AB  - OBJECTIVE: To investigate the role of oxidative stress in pathogenesis of
      polycystic ovary syndrome (PCOS), especially in the obese PCOS. METHODS: 43 PCOS
      patients with BMI > or = 23 kg/m2 were grouped into PCOS1. 42 PCOS patients with
      BMI < 23 kg/m2 were grouped into PCOS2. Meanwhile, 85 infertility patients with
      normal endocrine function and body weight were grouped into control group. All
      patients were subjected to the measurement of serum levels of superoxide
      dismutase (SOD), 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) and visfatin. The
      difference among PCOS1, PCOS2 and control group were compared and the
      relationships between the indexes were analyzed with simple liner regression
      analysis. RESULTS: The serum level of SOD in PCOS1 and PCOS2 were lower than that
      in the control group (P < 0.05), and the serum level of SOD in PCOS1 was lower
      than that in PCOS2 (P < 0.05). The serum levels of 8-iso-PGF2alpha and visfatin
      in PCOS1 were higher than those in PCOS2 and control group (P < 0.05). The serum
      levels of 8-iso-PGF2alpha and visfatin between PCOS2 and control group were not
      statistical different. In PCOS1 and PCOS2 groups, SOD activity decreased with
      increasing levels of 8-iso-PGF2alpha, the regression coefficient was -0.407. For
      serum vifation, there were positive correlations with both BMI and 8-iso
      PGF2alpha, but negative correlation with SOD; the coefficients were 0. 402 (P =
      0.008), 0.612 (P = 0.000), and -0.153 (P = 0.000), respectively. The indexes
      mentioned above did not have the liner relationship in the control group.
      CONCLUSION: There was oxidative stress in PCOS patients, which was not obvious in
      the normal weight PCOS patients but quite severe in the obese PCOS patients.

PMID- 22650029
TI  - [Retinal nerve fiber layer and macular thickness in the fellow eyes of patients
      with anisometropic amblyopia].
AB  - OBJECTIVE: To measure the retinal structure of the fellow eyes of patients with
      anisometropic amblyopes with retinal nerve fiber layer thickness (RNFLT), macular
      thickness (MT), and their correlations with axial length (AL) and spherical
      equivalent (SE). METHODS: AL was measured by IOLMaster. RNFLT and MT were
      obtained through optical coherence tomography (OCT). The data of the 56
      unilateral amblyopes (56 fellow eyes) were compared with those of 170 normal eyes
      from 85 age-matched people. RESULTS: The fellow eyes had thicker RNFLT (RNFLT
      fc), temporal RNFLT (RNFLT-t) and inferior (RNFLT-i); and thinner nasal RNFLT
      (RNFLT-n) than the normal eyes. But no statistically significant differences in
      superior RNFLT (RNFLT-s) and MT were found between the fellow eyes and normal
      eyes. After adjustments for age, gender and AL or SE, only the change of RNFLT-t
      remained significant (P < 0.05 ). Partial correlation analysis between the
      thickness values and AL/SE adjusted for age and gender showed different trends
      between the fellow eyes and normal eyes. Multiple linear regression adjusted for
      age and gender also obtained different coefficients between the fellow eyes and
      normal eyes. Independent sample t test found no difference in thickness
      parameters between occlusion and non-occlusion eyes in patients with
      anisometropic amblyopes. CONCLUSION: Fellow eyes of patients with anisometropic
      amblyopes have subnormal retinal structure despite a normal corrected visual
      acuity. Occlusion does not affect the retinal structure. AL or SE can affect the
      measurements of RNFLT.

PMID- 22650030
TI  - [Superior attachment of renal fascia: a study with multidetector computed
      tomography and three dimensional reconstruction].
AB  - OBJECTIVE: To observe the superior attachment of renal fascia (RF) and the
      perirenal space (PS) in order to identify the spreading pathway of inflammatory
      and malignant tumors. METHODS: Multidetector computed tomography (MDCT), with
      double phase enhancement scanning and three dimensional reconstruction of images
      were performed on 121 healthy adults. The RF attachments upward were observed and
      their connections with the PS were evaluated. RESULTS: The left anterior renal
      fascia (ARF) fusing with peritoneum accounted for 27.3% (33/121) and the left ARF
      fusing with peritoneum of the spleen laterally and with the subdiaphragmatic
      fascia interiorly accounted for 19.8% (24/121) of the upper attachments of the RF
      above the upper renal pole (URP). Under the URP, the left ARF fusing with
      peritoneum accounted for 52.9% (64/121) of the upper attachments of the RF. The
      right ARF fusing with peritoneum did not display above the URP. The posterior
      renal fascia (PRF) of both side fused with subdiaphragmatic fascia under the URP.
      The ARF and PRF of the left and right kidney showed no upward integration. The
      right PS communicated with the subdiaphragmatic retroperitoneal space (SDRS) that
      is a bare area of the liver. The left PS communicating with the SDRS accounted
      for 80.2% (97/121) and the left PS communicating with the SDRS laterally but
      separating from the SDRS interiorly accounted for 19.8% (24/121) of the SDRS
      communication. CONCLUSION: MDCT and three-dimensional reconstruction can
      remarkably display RF and its superior attachment, as well as the connection
      between the PS and SDRS.

PMID- 22650031
TI  - [Long term effectiveness of vaccination of Hepatitis A].
AB  - OBJECTIVE: To develop a dynamic model of Hepatitis A transmission in order to
      predict the long-term effectiveness of Hepatitis A vaccination on 18 months old
      infants and 2 to 18 years old children. METHODS: A dynamic model of HA (S-E-I-R
      V) was developed using the software Berkeley-Madonna. The parameters required for
      the model derived from literature. A sensitivity analysis was performed to assess
      the stability of the model through changing parameters. RESULTS: During the
      period of 2010 to 2030, the cumulative cases of Hepatitis A would reach 7.8
      million with an incidence of 38.8 per 100,000 without vaccination. With 38% to
      57% coverage of vaccination in children of 1.5-18 years old, the cumulative cases
      would decrease to 4.36-4.75 million with an incidence of 17.5-19.4 per 100,000.
      The vaccination was predicted to reduce 3.06-3.45 million Hepatitis A cases with
      an incidence reduction of 19.4-21.3 per 100,000. This suggests that Hepatitis A
      vaccination would achieve a 54% decrease in incidence of Hepatitis A. The
      sensitivity analysis showed that the coverage of vaccination had a significant
      impact on the incidence of Hepatitis A. By 2030, the incidence of Hepatitis A
      would decrease from 19.4 per 100,000 to 16.0 per 100,000 when the vaccination
      coverage increases from 38% to 90%. CONCLUSION: Hepatitis A vaccination can
      effectively prevent and control the incidence of Hepatitis A.

PMID- 22650032
TI  - [Finite element analysis and static biomechanics of pelvic after modular
      hemipelvic prosthesis reconstruction].
AB  - OBJECTIVE: To compare the stress distribution of normal pelvis with those of
      postoperative contralateral pelvic and modular hemipelvic prosthesis under
      different positions, with an aim to providing biomechanical evidence support for
      safe reconstruction of pelvic ring using modular hemipelvic prosthesis. METHODS:
      Three-dimensional finite element models of normal pelvis, postoperative pelvic
      and modular hemipelvic prosthesis were established using thin-layer CT scanning
      (TLCS). The stress distributions of normal pelvis, postoperative pelvic and
      prosthesis were measured under three static positions: standing on two feet,
      standing on one foot on the defective side and sitting. RESULTS: Little
      difference was found in contralateral pelvic stress between the normal pelvic and
      reconstructive pelvic models given the same load with different positions. The
      maximum stress level appeared at the upside of sacrum mesion, sacroiliac joints,
      superior greater sciatic notch and iscbial tuberosity, albeit a much lower level
      than fatigue strength. The maximum stress level of modular hemipelvic prosthesis
      appeared at the inner wall of connector bar between CS fixation and acetabular
      cup. Similarly, the stress level was also much lower than the fatigue strength of
      connector bar. The stress distribution of postoperative pelvic was similar to
      that of normal pelvic. CONCLUSION: Reconstruction with modular hemipelvic
      prosthesis has little effect on contralateral pelvic. The maximum stress levels
      of contralateral pelvis and modular hemipelvic prosthesis are significantly lower
      than their fatigue strength, which indicates sound safety of contralateral pelvis
      and modular hemipelvic prosthesis. Pelvic reconstruction with modular hemipelvic
      prosthesis produces good biomechanical compatibility.

PMID- 22650033
TI  - [Epidemiological survey on neuropsychiatric disorders in Tibet of China:
      neuroses, alcohol-related disorders, mental retardation and epilepsy].
AB  - OBJECTIVE: To investigate the prevalence of four common neuropsychiatric
      disorders in Tibet, with an aim to providing information support to health
      planning. METHODS: The survey was carried out in four regions of Tibet. The
      sampling strategy was adapted from that of a national psychiatric epidemiological
      survey in China in 1982 and 1993. The Neurosis Screening Inventory, Screening
      Inventory for Alcohol Dependence and Related Problems, Child Intelligence
      Screening Inventory, and a questionnaire for the Detection of Epileptic Seizures
      were administered to the respondents through face to face interview. Those with a
      positive response and 10% of those with a negative response were further
      interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders
      (research version) (SCID-I ). Anxiety disorders and alcohol used disorders were
      diagnosed according to the American Psychiatric Association: Diagnostic and
      Statistical Manual of Mental Disorders (4th edition) (DSM-IV). Hysteria and
      mental retardation were diagnosed according to the International Classification
      of Diseases, 10th edition (ICD-10), and the Chinese Classification of Mental
      Disorders, 3rd edition (CCMD-3). RESULTS: The point prevalence of neuroses,
      alcohol-related disorders, mental retardation and epilepsy was 2. 56%, 4. 06%, 0.
      28% and 0. 68%, respectively. The lifetime prevalence of neuroses, alcohol
      related disorders, mental retardation and epilepsy was 2. 62%, 4. 24%, 0. 28% and
      0.72%, respectively. CONCLUSION: Alcohol-related disorders and neuroses are the
      two common mental health problems in Tibet. Mental retardation and epilepsy are
      the two serious neuropsychiatric disorders affecting Tibetan children and
      adolescence. These disorders should be identified as priorities in the reginonal
      health planning in Tibet.

PMID- 22650034
TI  - [Risk factors of perinatal blood transfusion].
AB  - OBJECTIVE: To investigate the risk factors associated with perinatal packed red
      blood cell transfusion. METHODS: We performed univariable analysis and
      unconditional multivarible logistic regression analysis to identify risk factors
      associated with perinatal packed red blood cell transfusion in 19 456 obstetrical
      inpatients. RESULTS: The transfusion rate was 1.49% (289/19,456). Prenatal
      hematocrit (HCT) less than 25% (OR 45.3, 95% CI 27.4-74.9), placenta previa (OR
      16.8, 95% CI 11.6-24.3), prenatal HCT 25%-30% (OR 11.4, 95% CI 6.7-19.7), ethnic
      minority (OR 4.8, 95% CI 1.6-14.0), placenta abruption (OR 4.5, 95% CI 1.7-11.5),
      multiple gestation (OR 2.8, 95% CI 1.6-4.9) and preeclampsia (OR 2.6, 95% CI 1.5
      4.4) were risk factors associated with perinatal packed red blood cell
      transfusion. CONCLUSION: Although the overall perinatal transfusion rate is low,
      severe prenatal anemia (HCT 25%) and placenta previa can increase the risk of
      transfusion markedly. It is crucial for obstetricians to provide appropriate
      perinatal care for those patients.

PMID- 22650035
TI  - [Activities of daily living and demand for care of the elderly with chronic
      conditions in Chengdu].
AB  - OBJECTIVE: To evaluate the activities of daily living and demand for care of the
      elderly with chronic conditions in Chengdu in order to develop appropriate care
      models. METHODS: Convenient sampling strategy was adopted to recruit participants
      in four communities in Chengdu. A total of 180 elderly respondents with chronic
      conditions completed a questionnaire survey, which evaluated the activities of
      daily living and demand for care of the respondents. RESULTS: More than 77%
      respondents suffered from two or more chronic conditions. Over 97% respondents
      followed medical advices of doctors in drug therapy, with 70% monitoring the
      effectiveness of the drug therapy by themselves. The chronic conditions of 61% of
      respondents were well controlled. More than 54% were able to perform activities
      of daily living; 38% needed assistance; and 8% were completely dependent on
      others. Age and numbers of conditions influenced the activities of daily living
      (P < 0.005). Over 98% respondents were aware of their care needs and 1%
      identified unmet needs. Care for elderly came mainly from families, followed by
      relatives, friends, neighbors and workmates. Demands for care depended on
      financial capacity, degree of independence and numbers of conditions. Demands for
      nursing care increased with numbers of conditions (P < 0.05). CONCLUSION: The
      ability of elderly performing activities of daily living decreases with age and
      chronic conditions. A multidimensional care model involving professional carers
      needs to be developed in responding to the increasing needs of aged care.

PMID- 22650036
TI  - [Prevention of falls of hospitalized elderly patients using clinical pathway].
AB  - OBJECTIVE: To explore effective strategies for preventing falls of hospitalized
      elderly patients using clinical pathway. METHODS: A total of 2442 patients aged >
      or = 70 years who were hospitalized during December 2009 and December 2010 were
      recruited for the study. The patients were assessed with "Falls Risk Assessment
      and Nursing Care Inventory" and 1796 were identified as with high risk of falls.
      The clinical pathway for preventing falls was applied to those patients with high
      risk of falls. The interventions included timely assessments, safe environment
      and facilities, targeted health education, extended nursing care on patients with
      high risk, improved hand-off, rational use of medicine, and so on. RESULTS: Only
      4 patients fell, with an incidence of 0.22%. Sex, age, disease, psychological
      factors, clothing, hospital environment, drug effects, and history of falls were
      associated with the occurrence of falls. CONCLUSION: Risk assessment and targeted
      intervention through clinical pathway are effective strategies for preventing
      falls of hospitalized elderly patients.

PMID- 22650037
TI  - [From research of BDNF in traumatic brain and spinal cord injury to translational
      medicine].
AB  - Brain and spinal cord injury (BSI), a common neurological disease, is increasing.
      The functional recovery of BSI is far from satisfactory despite great improvement
      in clinical treatment of BSI. Research into injury of neurons and neurite as well
      as the microenvironment that regulate BSI conditions should be able to enable us
      to find a pivotal position among the complex molecular system for effective
      clinic practice. Further effort needs to pay attention to translational research.
      In this paper, we propose a crucial molecule, known as brain derived neurotrophic
      factor (BDNF), for translational research in relation to BSI because of its
      significant role in BSI and its changes with various interventions such as
      acupuncture, hormone, herb and cell agents. Moreover, the establishment of BDNF
      transgenic release would provide a practical approach for treating BSI with BDNF.
      It is important that research questions derive from bedsides (what do doctors and
      patients need?). Answers identified by laboratory research should be put into
      practice (back to bedsides). This consists of B-to-B double circles. As a key
      concept of translational medicine, it will guide our direction towards optimal
      development of medical research and medical practice.

PMID- 22650038
TI  - [Implication of BDNF expression in transected spinal cord of rats].
AB  - OBJECTIVE: To explore the change of brain derived neurotrophic factor (BDNF)
      expression and its relationship with the neurological behavior after spinal cord
      transection (SCT) in rats. METHODS: 66 adult SD rats were assigned randomly to
      sham operation group and SCT group. Rats in SCT group were subjected T10-T11
      spinal cord transection and allowed to survived 1 d, 3 d, 7 d, 14 d, 21 d and 28
      d. BBB scores in hindlimbs were observed at 0, 7, 14, 21 and 28 days post
      operation (dpo). The BDNF expression was determined by using ELISA (28 d) and RT
      PCR (each time point) techniques. The localization of BDNF and its mRNA at sham
      and 28 d after SCT was also observed by immunohistochemistry and in situ
      hybridization. RESULTS: After SCT, the motor function in hindlimbs disappear
      immediately. The BBB scores get a gradual recovery from 14 dpo to 28 dpo, when
      compared with that of former timepoint (P < 0.05). BDNF and its mRNA were located
      in cytoplasma and neurites. The level of BDNF mRNA (indicated by RT-PCR) was
      upregulated at 14 days after SCT than that in 1 and 3 dpo (P< 0. 05). The
      contents of BDNF in the injuried spinal cords at 28 dpo were increased than that
      in the sham operation group (P < 0.05). CONCLUSION: Neuroplasticity has occurred
      in rats subjected to SCT, and the mechanism may be involved in the increase of
      BDNF expression in the spinal cord with the time going.

PMID- 22650039
TI  - [Changes of BDNF expression in neurons in traumatic brain injury rats].
AB  - OBJECTIVE: To investigate changes of brain derived neurotrophic factor (BDNF)
      expression in neurons in traumatic brain injury (TBI) rats. METHODS: Adult SD
      rats were divided into sham and operated group resulted from hammer fall
      contusion (30 cm high, 50 g weight). Thirteen rats in each group were used. Some
      of animals (n = 6 in each group) were used to perform immunohistochemistry and in
      situ hybridization, and the other (n = 7) was used for RT-PCR. After NSS
      assessment was determined at 1, 3, 8, 13 days, TBI rats were sacrificed, brain
      tissues were then harvested to measure BDNF level. Data were analyzed by using
      statistic method. RESULTS: A increased NSS scores (P < 0.05) was observed after
      TBI, which implied the significant neurobehavioral changes in rats. But a gradual
      decreasing NSS scores (P < 0.05) was also observed along with time prolonged.
      Severe neurological severity function was seen following TBI, and it presents a
      gradual improvement indicated by decreasing NSS scores, despite BDNF mRNA level
      in whole brain tissue did not present a significant change, the BDNF expression
      (indicated by optical density values analysis) in subcellular structure, known as
      neurons, exhibited a significant increase, when compared with that of sham group
      (P < 0.05). This could simultaneously accompany with the decrease in the number
      of neurons in TBI rats. CONCLUSION: TBI rats exhibit a neuroplasticity with the
      BDNF upregulation in neurons following injury.

PMID- 22650040
TI  - [Effect of gold belt on the BDNF and NMDA receptor expression and behaviour
      changes in rats following traumatic spinal cord injury].
AB  - OBJECTIVE: To study the effects of gold belt (GB), a Chinese Herbal, on
      behavioral changes and brain derived neutrophic factor (BDNF) expression and N
      methyl-D-aspartic acid (NMDA) receptor level in rats subjected to spinal cord
      injury (SCI). METHODS: Adult male SD rats were randomly divided into three
      groups: (1) Sham group; (2) Spinal cord injury group (SCI group); (3) Spinal cord
      injury followed with gold belt treatment (gold belt 50 mg/(kg x d), intragastric
      gavage once daily for 7 days) group (GB group). The Basso, Beattie and Bresnahan
      (BBB) locomotor scale method was performed to evaluate the hindlimb motor
      function in the days 0, 3, 10 and 28. After 13 days, 8 rats in each group were
      treated with 1% sodium pentobarbital (30 mg/kg), myoloid tissue in T10 position
      was taken and stored in liquid nitrogen to detect NMDA receptor affinity and
      maximum binding amount (Bmax) with radioligand binding assay. After 28 days, rats
      were sacrificed and the spinal cords were harvested for immunohistochemistry to
      observe the localization of BDNF in the ventral and dorsal horn of the spinal
      cord. RESULTS: After spinal cord contusion, GB resulted in a significant increase
      on the number of BDNF positive neurons compared with traumatic group, and
      increased BBB score and decreased NMDA receptor were also found in GB group.
      Whereas decreased BDNF expression, NMDA receptor affininty (Kd) were observed in
      traumatic injury group. CONCLUSION: The gold belt treatment could effectively
      improve motor function, increase expression of BDNF, reduce the level of NMDA
      receptors in SCI rats. These data suggested that the gold belt played a role in
      the neuroplasticity after spinal cord injury.

PMID- 22650041
TI  - [Effect of methylprednisolone on neurological behavior and the BDNF and NMDA
      receptor expression after traumatic spinal cord injury in rats].
AB  - OBJECTIVE: To study the effect of methylprednisolone on spinal cord injury rats'
      neural behavior and the expression of brain derived neurotrophic factor (BDNF)
      and N-methyl-D-aspartic acid (NMDA). METHODS: To establish rat model of spinal
      cord injury (SCI), the rats were randomly divided into sham operation group, SCI
      group and methylprednisolone group (n = 16 in each group). Eight rats were used
      for the behavioral assessment and BDNF measurement,the other eight animals was
      for the NMDA receptor test in each group. Within 8 h spinal cord contusion,
      methylprednisolone (50 mg/kg) was injected for methylprednisolone group, then
      after that the intramuscular injection of methylprednisolone was per day
      reduction in 10 mg/kg, till 5 days. By using immunohistochemical staining, the
      distribution of BDNF in the spinal cord and positive cell localization was
      observed and the number of positive cells were counted. The NMDA receptor
      affinity (Kd) and maximum binding amount (Bmax) were measured with [3H] MK-801
      radioligand method, and the rat hind limb functional was also evaluated with BBB
      score analysis. RESULTS: Both the number of BDNF positive cells and the BBB score
      in methylprednisolone group was significant higher than that of SCI group; While
      increased receptor affinity (Kd) and decreased Bmax for NMDA receptor in
      methylprednisolone group was seen less than in SCI group (P < 0.05). CONCLUSION:
      Methylprednisolone can improve the function of rat hind limb, increase BDNF level
      and decreased NMDA receptor expression after spinal cord injury.

PMID- 22650042
TI  - [Effects of electroacupuncture of "governor vessel" acupoints on changes of BDNF
      in the cortical motor area of mice with spinal cord transection].
AB  - OBJECTIVE: To investigate effects of electroacupuncture of "Governor Vessel"
      acupoints on changes of brain erived neurotrophic facotr (BDNF) in the cortex
      area of mice with spinal cord transection (SCT). METHODS: GFP mices were made
      spinal cord transection between T9 and T10, and then divided into
      electroacupuncture group (EA group) and control group; mices of EA group had be
      given EA from 1 day postoperation to 14 day postoperation, however, mices of
      control group had only SCT. Immunohistochemistry, in situ hybridization, RT-PCR
      and ELISA were performed to observe changes of BDNF in the cortical motor area of
      EA and control group. RESULTS: At 28 d postoperation the protein expression of
      BDNF in the cortex area of EA group and control group was (1973.41 +/- 194.71)
      pg/kg and (1615.22 +/- 137.21) pg/kg respectively, and there was statistical
      difference between them (P < 0.05). However, there was no obvious different in
      expression of BDNF mRNA in the cortex area between EA and control group (P >
      0.05). The positive products of BDNF mRNA and protein were mainly located in
      neurons in the cortex area. CONCLUSION: EA in "Governor Vessel" can effectively
      induce the increases of BDNF protein in the cortex area which may be helpful to
      understand the mechanism of EA in the treatment of spinal cord injury.

PMID- 22650043
TI  - [Regulation of BDNF expression in traumatic brain injury rats subjected single
      neucleated cell transplantation].
AB  - OBJECTIVE: To investigate the effect of single neucleated cells transplantation
      on the neurological function and brain derived neurotrophic factor (BDNF)
      expression in traumatic brain injury (TBI) rats. METHODS: TBI rats were
      established by hammer fall method from 30 cm height with 50 g weight. Single
      neucleated cells/ karyocytes from bone marrow were separated and prepared by
      ficoll medium, then transplanted into pericontusional tissues in the brain.
      Neurological function severity scores (NSS) were recorded at 1, 3, and 7 days
      post operation (dpo). The pericontusional tissues were harvested at 7 dpo to
      analyze the BDNF localization, expressional level. RESULTS: Single neucleated
      cell transplantation decreased NSS significantly, compared with TBI rats without
      cell implantation (P < 0.05). BDNF expression was upregulated and mainly found in
      neurons. CONCLUSION: The present study showed the single karyocytes
      transplantation could improve neurological function and the mechanism is possibly
      linked to the BDNF expression.

PMID- 22650044
TI  - [Constrution of human single herpes virus carried BDNF gene vector and its
      bioactivity evaluation].
AB  - OBJECTIVE: To construct the recombinant vector of human single herpes virus (HSV)
      carried brain derived neurotrophic factor (BDNF) gene. METHODS: BDNF gene was
      acquired from rat brain tissue by RT-PCR, then was cloned into plasmid, and
      enveloped by HSV. The recombinant was used to transfer cultured cortical neurons.
      The number and neurite length of neurons were quantified. The BDNF level and
      subcellular localization were detected by ELISA and immunohistochemistry.
      RESULTS: HSV carried BDNF gene recombinant has been successfully constructed. The
      recombinant showed the bioactivity on the growth of cortical neurons. BDNF level
      was increased significantly in BDNF transferred group. CONCLUSION: HSV carried
      BDNF gene recombinant, with the bioactivity, has been successfully constructed.
      This could provide the vector for the treatment of BDNF under disease condition
      base on transferring gene technique.

PMID- 22650046
TI  - [In vitro analysis and in vivo tracing of BrdU-labeled rat bone marrow
      mesenchymal stem cells].
AB  - OBJECTIVES: To investigate the optimal condition of bromodeoxyuridine (BrdU)
      labeling for bone marrow mesenchymal stem cells (BMSCs) in vitro and the
      feasibility of in vivo tracing of BrdU-labeling BMSCs. METHODS: BMSCs were
      isolated from Wistar rats and were in vitro routinely cultured. The third passage
      BMSCs was used for identification of special surface antigens by
      immunohistochemical methods. The purified BMSCs were incubated with BrdU at
      different concentrations for different incubating time to investigate optimal
      BrdU concentration and incubating time for cell labeling. The cell labeling index
      of BrdU was calculated with immunohistochemical analysis. BMSCs labeled BrdU were
      injected into damaged gastric mucosa of rats by micro injector. The colonization
      of BMSCs labeled BrdU in gastric mucosa was viewed. RESULTS: After purification
      and proliferation, the primary cultured BMSCs were uniformly long spindle-shapped
      form and formed cell colony, which showed the characteristics of stem cell.
      Immunocytochemistry showed BMSCs were positive for CD44 and CD90, while negative
      for CD14, CD45. The labeling rate of BrdU increased with the labeling time
      lasting and reached its height at 48 h. After incubating 48 and 72 hours, the
      labeling rate of BrdU with a concentration of 10 micromol/L was higher than that
      of BrdU with a concentration of 5 micromol/L (P < 0.05) and similar with that of
      BrdU with a concentration of 15 micromol/L (P > 0.05). In addition, the BrdU
      labeling could be detected after five consecutive passages and the labeling time
      could keep 21 d. The pathological observation demonstrated that BrdU-labeled
      BMSCs could colonize the damaged gastric mucosa with normal morphologic
      characteristics during observation period. CONCLUSION: BrdU labeling might be a
      feasible method for dynamic observation of the migration, growth and
      differentiation of migrating BMSCs in colonizing sites.

PMID- 22650045
TI  - [Experiment study on the treatment of SCI based on HSV carried BDNF transgene
      technique].
AB  - OBJECTIVE: To explore the effect of brain derived neurotrophic factor (BDNF)
      transgenic treatment in rats following spinal cord injury (SCI). METHODS: BDNF
      gene was cloned into plasmid then enveloped with human single herpes virus (HSV)
      to construct HSV carried BDNF transgenic recombinant. BDNF recombinant was
      injected into sciatic nerve to last label in motorneurous in the caudal cords,
      then ventral motor neurons were counted and the area of cell body was measured.
      The BBB scores representing motor function in hindlimbs was also recorded.
      RESULTS: Five days were needed for the GFP-HSV to arrive motorneurons from
      sciatic nerve. BDNF release could increase the number of motroneurons and inhibit
      neuronal atrophy in injured spinal cord. BDNF administration also improves motor
      function in hindlimbs. CONCLUSION: BDNF transgene carried by HSV is a useful
      strategy for the treatment of SCI, indicating its clinic implication in future
      treatment.

PMID- 22650047
TI  - [Evaluation of papillary muscle function of patients with chronic ischemic mitral
      regurgitation using two-dimensional speckle tracking imaging].
AB  - OBJECTIVE: To evaluate the papillary muscle function of patients with chronic
      ischemic mitral regurgitation (IMR) using two-dimensional speckle tracking
      imaging. METHODS: 119 patients with chronic IMR and 94 normal controls were
      enrolled in this study. The peak systolic strain (PSS) and peak systolic strain
      rate (PSSR) of the papillary muscle were assessed with two-dimensional strain
      software. The PSS and PSSR were compared between the patients with anterior
      myocardial infarct (AMI) and those with inferior myocardial infarct (IMI). The
      correlation between the degree of IMR and the position of MI was analysed.
      RESULTS: The patients with chronic IMR had significantly lower PSS and PSSR than
      the normal controls. The IMI patients had significantly lower PSS and PSSR than
      the AMI patients. The IMI patients had significantly higher degree of MR than the
      AMI patients. CONCLUSION: Two-dimensional speckle tracking imaging is a reliable
      method for assessing papillary muscle function.

PMID- 22650048
TI  - [Visualization of right atrial flow patterns and quantification of pulmonary to
      systemic flow ratio in patients with atrial septal defect by vector flow
      mapping].
AB  - OBJECTIVE: To evaluate the ability of vector flow mapping (VFM) in visualizing
      right atrial flow and quantifying pulmonary to systemic flow ratio in patients
      with atrial septal defect (ASD). METHODS: VFM was performed on 30 patients with
      ASD and 50 healthy volunteers. The pulmonary to systemic flow ratio (Qp/Qs) was
      calculated using VFM and spectral doppler compared with that obtained through
      oximetric data derived from cardiac catheterization. RESULTS: Blood streams from
      superior and inferior caval veins did not collide but turned forward,
      contributing to a forward clockwise vortex during systole on the subcostal bi
      atrial plane in the healthy volunteers. The vortex was disrupted continuously by
      a left to right shunt in the patients with ASD during the hole cardiac cycle. The
      Qp/Qs measured by VFM was less angle-dependent in all the cases than the other
      methods. The mean value of Qp/Qs of the healthy volunteers calculated by apical
      three-chamber view and apical five-chamber view ranged from 0.84:1 to 1.15:1,
      which is consistent with the theoretical value 1 of no left to right shunts. The
      values of Qp/Qs of patients with ASD measured by VFM and spectral doppler showed
      no significant differences with those obtained through oximetric data [(2.18 +/-
      0.48) vs. (2.29 +/- 0.76), P = 0.29; (2.30 +/- 0.91) vs. (2.29 +/- 0.76), P =
      0.86]. However, the Qp/Qs value measured by VFM had a better correlation with the
      oximetric data than that measured by spectral doppler (r = 0.71, P < 0.001 vs. r
      = 0.38, P < 0.05). The inter-observer and intraobserver variability of Qp/Qs
      measured by VFM was 9.84% and 9.86% respectively. CONCLUSION: VFM can visualize
      right atrial flow field in patients with ASD and quantify Qp/Qs in a more
      accurate way than spectral dopler.

PMID- 22650049
TI  - [Predicting prostate cancers using a logistic regression model with transrectal
      ultrasound characteristics, age and serum PSA].
AB  - OBJECTIVE: To determine the value of transrectal ultrasound characteristics in
      combination with age and prostate specific antigen (PSA) for predicting prostate
      cancers. METHODS: 579 patients with prostate diseases were examined with color
      doppler, followed by biopsies of prostates. A logistic regression model was
      developed to determine the relationship between prostate cancers and transrectal
      ultrasound characteristics, age and PSA levels. RESULTS: The biopsy confirmed 194
      (33. 5%) prostate cancer cases and 385 (66. 5%) noncancerous patients with
      prostate diseases. The prostate cancer patients showed hypoechoic nodule, uneven
      echo, abnormal blood flow, abnormal prostate shape, unclear boundary of internal
      and external glands, unclear dividing line of prostate and seminal vesicle
      glands, unclear dividing line of prostate and rectal, and lymph node metastasis.
      Our prediction model had a 83.59% accuracy, 64.95% sensitivity, 92.99%
      specificity, 82.35% positive predictive value, and 84.04% negative predictive
      value. CONCLUSION: Transrectal ultrasound characteristics in combination with
      patients age and serum PSA is a good predictor of prostate cancer.

PMID- 22650050
TI  - [Clinical outcomes of surgical patients with types II and III adenocarcinoma of
      esophagogastric junction].
AB  - OBJECTIVE: To investigate the clinical pathological characteristics, choice of
      surgical therapy and postoprative complications of patients with types II and III
      adenocarcinoma of esophagogastric junction (AEG). METHODS: Clinical data of 112
      patients with types II and III AEG who underwent intraperiteanal operations from
      January 2008 to July 2010 were reviewed. Amongst the patients, 77 suffered from
      type II AEG and 35 suffered from type III AEG; 72 underwent proximal gastrectomy
      and 40 underwent total gastrectomy. RESULTS: The patients with type II and type
      III AEG shared some common characteristics, such as advanced tumor TNM stage and
      lymphatic metastasis. There was a significant difference in choice of surgical
      approaches between the two groups of patients (P < 0.05), with 57 type II AEG
      patients (74.0%) and 15 type III AEG patients (42.9%) undergoing proximal
      gastrectomy respectively. Operational time and incidence of postoperative
      complications differed between proximal gastrectomy and total gastrectomy (P <
      0.05). Total gastrectomy lasted longer [(304.12 +/- 23.12) min] than proximal
      gastrectomy [(275.76 +/- 27.02) min]. Proximal gastrectomy provoked 20.8% (15
      patients) heartburn and/or acid regurgitation and 12.5% (9 cases) reflux
      esophagitis. Fifteen patients (37.5%) with total gastrectomy had more than 5
      meals a day. CONCLUSION: Intraperiteanal operations are recommended for patients
      with types IT and Ili AEG. The choice of proximal gastrectomy or total
      gastrectomy depends on the location and size of the tumor, both being followed
      with some complications.

PMID- 22650051
TI  - [Prognosis of patients with adrenocortical carcinoma].
AB  - OBJECTIVE: To investigate the prognosis and influencing factors of patients with
      adrenocortical carcinoma. METHODS: Thirty-five patients (20 males and 15 females)
      with biopsy-diagnosed adrenocortical carcinoma were followed retrospectively. Cox
      proportional hazards regression analysis was performed to identify factors that
      influenced the prognosis of the patients. RESULTS: Three patients were classified
      as stage I, 15 as stage II, 12 as stage III, and 5 as stage IV. Fourteen patients
      were still alive and 21 died at the end of the follow-up. The patients had a
      median survival time of 33 months, with a survival rate of 77.1%, 62.5%, and
      38.3% for the first year, second year, and fifth year respectively. The
      univariate analysis found no significant differences in survival rates with
      gender, tumor location (left or right adrenal), diameter (> or = 10 cm or <10 cm)
      of tumor, functionality of tumor, smoking, hypertension and hypokalemia (P >
      0.05). The multivariate analysis revealed that being male, younger than 50 years,
      non-smoking and early-stage of tumor were significant protective factors for the
      survival of patients with adrenocarcinoma. Patients at stage III and stage II had
      52 and 3 times higher mortality than those at stage I, respectively. CONCLUSION:
      Clinical stage and age are the main factors that influence the survival of
      patients with adrenocortical carcinoma. Patients younger than 50 years and those
      with an earlier stage of tumor would have a better prognosis.

PMID- 22650052
TI  - [Clinical analysis of patients with acute and severe mental disorders complicated
      with hypokalemia].
AB  - OBJECTIVE: To study the occurrence and characteristics of hypokalemia to the
      patients with acute and severe mental disorders, and analyze its influencing
      factors. METHODS: There were 815 patients with actue and severe mental disorder
      admitted into our psychiatry department from June 2009 to May 2010, who all
      received the examination of potassium concentration routinely at the admission.
      The patients were divided into hypokalemia group and non-hypokalemia group, and
      the clinical information were surveyed and compared between the two groups to
      find out the influencing factors of hypokalemia. RESULTS: There were 177 patients
      with hypokalemia, and the proportion was 21.72%. Between the two groups, the
      difference of age, sex, admission season, whether with physical diseases and
      diagnosis were statistically significant (P < 0.05), while spiritual movement
      situation was not significant different (P > 0.05). Spearman rank correlation
      analysis showed that the incidence of hypokalemia was negatively correlated with
      age (r = -0.55, P = 0.00). Furthermore, multivariate analysis found that women,
      poor diet and physical disease were risk factors of hypolalemia (P < 0.05).
      CONCLUSION: There is relatively high probability of hypokalemia occurrence to the
      patients with acute and severe mental disorders, which should be distinguished
      and treated at the admission timely.

PMID- 22650053
TI  - A slew of science in Seattle: CROI served up a snapshot of HIV's Envelope trimer
      and the latest on PrEP and protective immune responses.

PMID- 22650055
TI  - Stalking HIV's sleeper cells: this year's HIV pathogenesis meeting focused on
      latent HIV reservoirs--and how they might be eradicated.

PMID- 22650054
TI  - Tapping the sanguine humor: broadly neutralizing antibodies stole the show at
      Keystone.

PMID- 22650056
TI  - WHO updates guidelines on ARV treatment.

PMID- 22650057
TI  - Global HIV vaccine enterprise appoints new director.

PMID- 22650059
TI  - CD4+ T cells can control viral load by directly killing HIV-infected cells.

PMID- 22650058
TI  - Predicting the antiviral activity of three-drug combinations in HAART.

PMID- 22650060
TI  - [Experimental approaches to investigation into the role of the genotype by the
      locus TAG 1A of dopamine D2-receptors in epileptogenesis].
AB  - The effect of genotype in locus TAG 1A of gene receptor dopamine second type on
      characteristics of peak-and-wave EEG pattern in somatosensory, parietal and
      occipital areas of the cortex was studied in two groups of rats. Quantitative
      analysis showed that the peak-wave discharge of the first type in rats with A1/A1
      genotype had a significantly longer duration, occurred more frequently leading to
      a significant increase in their peak-wave index. The results are of clinical
      interest creating a theoretical basis for improved diagnosis of absence epilepsy
      and selection of anticonvulsants.

PMID- 22650061
TI  - [Activity of lactate dehydrogenase in the brain cortex and hippocampus of
      Mongolian gerbils after global ischemia and reperfusion injuries].
AB  - Cerebral ischemia results in severe derangements of energy metabolism in the
      nervous tissue including activation of glycolytic pathway. Activity of cytosolic
      lactate dehydrogenase (LDH) in the specific brain structures remains unclear. The
      recent study was aimed at investigation into the LDH activity in the cytoplasm of
      both hippocampal and cortical neurons in Mongolian gerbils (Meriones
      unguiculatus) at different durations of reperfusion after global ischemia.
      Analysis showed that the activity of LDH in pyramidal neurons of various
      hippocampal areas and neurons of II, III and V cortical layers after 7-minute
      forebrain ischemia depended on both localization of the neurons and duration
      ofreperfusion. In general, the changes in postischemic cytosolic LDH activity
      include significant decrease in the LDH activity 2 days after reperfusion with
      varying degree of recovery on day 7 of reperfusion.

PMID- 22650062
TI  - [T-lymphocyte subpopulations and immune response in mice of the ASC strain with
      depressive-like behaviour].
AB  - Analysis of the content of CD16/32+, CD4+ and CD8+ -cells was perfomed in the
      peripheral blood and spleen ofmice of the ASC strain with high predisposition to
      depressive-like state in comparison with mice of parent CBA strain having no
      depressive behaviour. In both cases, ASC mice showed a decrease in the percentage
      of CD16/32+ and CD4+-cells along with an increase CD8 cells and lowering of
      immunoreactivity index (CD4+/CD8+). Changes in cellular subpopulations found in
      intact ASC mice was accompanied with animals' low capacity to respond to T
      dependent antigen: sheep red blood cells at the dose of 5 x 10(8). In contrast to
      CBA mice the percentage and absolute number of IgM-antibody-forming cells were
      significantly decreased in the spleen of ASC mice on the 4th and 5th days after
      immunization as well as the numbers of IgG-antibody-forming cells on the 6th day
      of the immune response. Possible mechanisms underlying the immune reactivity
      inhibition under depressive-like state are discussed.

PMID- 22650063
TI  - [The effect of ethanol exposure in pregnancy on maturation of monoaminergic
      systems in the developing rat bran].
AB  - Simultaneous study of the main neurotransmitter of monoaminergic system of the
      brain, its metabolites, activity of catechol-O-methyltransferase (COMT) and the
      state of different subtypes of dopamine (DA) receptors in the developing brain of
      offspring from mothers alcoholized in gestation and feeding periods revealed a
      decrease in activity of all monoaminergic systems studied with reduction of
      noradrenaline and DA level in alcoholized fetus as well as of mPNA of COMT, an
      enzyme of catecholamine metabolism, in the structures of the forebrain on the
      17th day but not on 13th day of prenatal development. In parallel experiments, an
      increase of the contents of both long and short splice variants of D2 DA receptor
      was registered. In postnatal period (days 4, 10, 17), further decrease of the DA
      system activity was observed, particularly a reduction of DOPAC level and
      DOPAC/DA ratio in rat litter, mothers of whom took alcohol in the gestation
      period with withdrawal it after birth of offspring. The serotonin system activity
      was also reduced in alcoholized litter in the postnatal period and was registered
      in the early stages (on the 4th day of life). Therefore, the serotonin system
      activity is changing at early stages of development (the 4th day), whereas
      inhibition of the DA system activity is registered at later stages (the 10th day
      of life).

PMID- 22650064
TI  - [Level of neuroactive steroids in the brain, and gender-related differences in
      formation and decrease of conditioned reflex in rats].
AB  - We investigated gender-related differences in dynamics of the brain sexual
      steroids during learning and the decrease of conditioned reflex in the modeling
      experiment. It was revealed that, before training to conditioned reflexes,
      females manifested a greater anxiety than males. Significant differences between
      males and females in formation of the conditioned reflex of passive avoidance
      were not revealed, whereas the conditioned response decrease were by 2-3 days
      faster in male rats than in females. It was revealed that there was an increase
      of testosterone content in various structures of the brain, especially in
      hippocampus and frontal cortex with its constant level in the blood plasma in
      learning conditioned response of passive avoidance in male adult rats. Also an
      increased estradiol concentration was found in females' amygdale, while increased
      value of estradiol was detected in hippocampus and the singular cortex in
      decrease of the conditioned response of passive avoidance. In blood plasma, the
      testosterone level was not changed, and the estradiol concentration was reduced
      significantly after the decreased conditioned reflex. Different dynamics of
      changes in the levels of sex steroids in the brain and the blood plasma can
      indicate a probability of their formation in nervous tissue. The correlation
      analysis confirms the conception about selective involvement of the brain's
      testosterone and estradiol in the specific structures in realization ofthe
      learning and memory processes in adult male and female rats.

PMID- 22650065
TI  - [The meaning of the auditory sensory systems asymmetry in highly coordinated
      manual movement].
AB  - Analysis of the stable correlation of asymmetry of the acoustic stem evoked
      potentials intervals with parameters of bimanual coordination was performed.
      Different mechanisms of the auditory asymmetry at the stem level were found in
      men and women. Optimum bimanual performance in men is provided by adequate co
      adjustment of sensor-motor system elements, and is connected with sensory input
      and the feature of its bilateral irradiation through the right input. The left
      channel input and its sensory asymmetry is much more important in women.
      Bilateral irradiation in this case does not lead to adequate integration of the
      systems elements in performance of the motor task, that indicates the lower level
      of bimanual coordination.

PMID- 22650066
TI  - [Influence of nanosize particles of cobalt ferrite on contractile responses of
      smooth muscle segment of airways].
AB  - Contractile responses of airways segments of porpoises inhaling nanopowder
      CoFe2O4 were stidued by means of a mechanographic method. Inhalation of the
      nanosize particles of CoFe2O4 in vivo and in vitro testing the nanomaterial on
      isolated smooth muscles led to potentiation histaminergic, cholinergic
      contractile activity in airways of porpoises and to strengthening of adrenergic
      relaxing answers. Nanosize particles vary amplitude of hyperpotassium reductions
      in smooth muscle segments of airways similarly to the effect of depolymerizing
      drug colchicine.

PMID- 22650067
TI  - [Adrenaline potentiates antiepileptic but not sedative action of diazepam in
      rats].
AB  - Intramuscular (i.m.) administration ofdiazepam in a dose of 10 mg/kg and
      adrenaline in a dose of 0.2 mg/kg prevents generalized clonic-tonic
      pentylenetetrazol (PTZ) seizures in 75-80 % of rats, but only in 35-40 % of rats
      it prevents local clonic PTZ seizures. In the above mentioned dose, diazepam
      causes a strong sedation, but adrenaline does not cause a sedative effects. The
      combined administration of diazepam and adrenaline in threshold independently
      ineffective doses prevents both clonic-tonic and clonic PTZ seizures in 80 % of
      rats without a sedation development. The basis for mechanism of potentiation of
      anticonvulsant action of diazepam is the stimulation of gastric mucosa afferents
      by adrenaline.

PMID- 22650068
TI  - [Determination of circulation disturbance in the rat lungs in modelling of
      chronic obstructive disease].
AB  - Development of chronic obstructive pulmonary disease (COPD) involves not only the
      bronchial and respiratory areas of the lungs, but also the system of pulmonary
      circulation, which begins with the defeat of capillary blood flow. One of
      radiological methods of studying lung microcirculatory functions is perfusion
      scintigraphy. We designed the technique of radiological examination and
      identified its abilities in determination of the role of vascular dysfunctions in
      experimental model of development of COPD. We assessed the results of
      pharmacological agents that affect the microcirculatory bed of the lungs and
      smooth muscles of pulmonary arteries in rats. Studies have shown the promise of
      the possibility of using the drug sulodexide for studying impaired endothelial
      function in clinical practice.

PMID- 22650069
TI  - [The similarity and difference in the action of adriamycin and hydrogen peroxide
      on the myocardium].
AB  - The oxidative stress in cardiomyocytes is a component of cardiotoxic action of
      adriamycin. To distinguish the importance of this component we have compared
      initial effects of hydrogen peroxide and adriamycin on the contractile function
      and a tone of coronary vessels of the isolated rat heart. Adriamycin in
      concentration 3 mcM distinctly reduced developed pressure and heart rate, but
      raised coronary vessel tone. The concentration 1 mcM was inefficient at usual
      perfusion rate, but practically prevented rise in developed pressure and rates of
      its rise and fall at increased perfusion rate. Hydrogen peroxide also dose
      dependently reduced developed pressure, but rates of its rise and fall were
      reduced to a lesser degree, while the heart rate slightly raised, and coronary
      vessel tone was reduced. Thus, the initial actions of hydrogen peroxide and
      adriamycin on the heart considerably differ. It suggests that the oxidative
      stress is not the main component of cardiotoxic action of adriamycin, at least,
      in its application in concentrations close to therapeutic ones.

PMID- 22650070
TI  - [Mechanism of outercellular [K+] in generation of pacemaker action potentials in
      sinoatrial valve of the rabbit].
AB  - In a control solution (solution I; 3 mM K+, 35 degrees C) the amplitude of APs of
      cells in the valve centre was 81 +/- 6 mV (Mean +/- SEM), the maximal upstroke
      velocity (dV/dtmax) was 19 +/- 4 V/s, velocity slow diastolic depolarization (DD)
      - 65 +/- 8 mV/s, the rate of spontaneous AP generation was 135 +/- 14 bpm. Hypo
      K+ (50 %) solution (solution II) decreased slow DD by - 22 % and dV/dtmax by -58
      % and the rate of AP generation by 15 % compared to the control solution. In
      saline solution, decrease of Emax from -68 to -45 mV and four-fold decrease of
      slow DD and dV/dtmax were registered at the 8th of exposure. After that the Emax
      noise and origin of early (EADs) and delay (DADs) afterdepolarizations were
      observed. Comparative analysis of the main AP parameters of SA valve latent
      pacemaker cells in solution III (without K+) and solution IV (without KC1 and
      CaCl2) exposure demonstrated that changes of this parameters in solution IV were
      less then in solution III. It is interesting that in solution IV exposure the
      phase of the early repolarization (phase 1) was differentiated, dV/dtmax was
      increased by 21%. The frequency of AP generation decreased by 18 % as in solution
      with 50% K+. At the same time, EADs were not registered. It seems that the
      decreasing of the transsarcolemal gradient of K+ depolarized Emax despite Nernst
      equation. At the same time permeability was decreased for K+ and Na+ ions. That
      could involve Ca2+ overload and origin of EADs and DADs.

PMID- 22650071
TI  - [Dynamic of myocarditis development in rats after injection of cardiac myosine
      combined with IFA].
AB  - Myocarditis development was investigated after immunization rats with single
      subcutaneous injection of cardiac myosin (800 microg/kg) with incomplete Freund's
      adjuvant (IFA) (M + IFA group). Control group received equal volume of IFA alone
      or nothing (intact group). On days 4, 14, and 21 after injection, light and
      electron microscopy of heart sections, morphometric analysis, estimation of
      proinflammatory cytokines (IL-1p, IL-6, VEGF, TNFa and iNOS) expression were used
      to evaluate inflammatory response in myocardium. In addition, we estimated
      cardiac myosin antibody levels in blood serum and nitrite and nitrate levels in
      blood serum. Our data showed that immunization with cardiac myosin combined with
      IFA led to inflammatory response in the rat myocardium. Acute inflammation (i.e.
      lymphocyte infiltration of myocardium and increase of proinflammatory cytokines
      level) in M + IFA group occurred on 21 days after immunization.

PMID- 22650072
TI  - [Effects of recombinant mechano-dependent growth factor against the background of
      chronic alcoholisation in rats].
AB  - In alcoholised rats, proliferation of satellite cells consistently decreased as
      well as the number of myonuclei, while phosphorylation of p90RSK became reduced.
      The mechano-growth factor abministration increased the proliferate activity of
      the myogenic precursors and restored the myonuclei pool. Phosphorylation of
      p90RSK increased too.

PMID- 22650073
TI  - [Stressogenic exposure of local vibration to energetic metabolism of the heart,
      liver and kidney of rats].
AB  - The purpose of the paper was to study the activity of energy producing system of
      the rabbit myocardium, liver and kidneys after exposure to local vibration during
      7 days. The energy dependent reactions of native mitochondria were investigated
      by means of polarographic method using dark closed membrane electrode. The
      intensivity ofoxydative processes was assessed according to activity of the
      lymphocyte succinate dehydrogenase and catalase of the blood. The energy
      producing system of the tissues studied was shown to be involved in response
      reaction of the organism on vibration exposure. In that case we observed the
      formation of the second phase ofbioenergy hypoxia in the myocardium and kidneys
      and the first phase ofhypoxia in the liver.

PMID- 22650074
TI  - [Analysis of properties of single molecules in vivo or ... why small fish is
      better than empty dish].

PMID- 22650075
TI  - [Cyto B dependent and ouabain insensitive regulatory volume decrease in
      bicellular mouse embryo].
AB  - Mouse single-cell embryos exhibit robust Regulatory Volume Decrease (RVD). In
      what manner the very early mammalian embryo following zygote stage is appreciably
      altered by the anisotonic extracellular solution is, as yet, totally unclear.
      Little attention was paid to this direction since there was no way to determine
      the blastomere volume. This work has served to quantitatively investigate the
      osmotic response of bicellular mouse embryos employing Laser Scanning
      Microtomography (LSM) followed with three-dimensional reconstruction (3 DR). We
      have shown that bicellular mouse embryos in hypotonic Dulbecco's experience RVD.
      Embryonic cells subjected to hyposmolar exhibit rapid osmotic swelling followed
      by gradual shrinking back toward their original volume. The van't Hoff law
      defines swelling phase with the effective hydraulic conductivity of 0.3 micron x
      min(-1) x atm(-1). Water release during RVD in bicellular mouse embryos is
      abolished by Cytochalasin B (Cyto B) and the volume recovery is insensitive to
      ouabain treatment.

PMID- 22650076
TI  - [Transmembrane transport of K+ and Cl- during pollen grain activation in vivo and
      in vitro].
AB  - We studied the possibility of K+ and Cl- efflux from tobacco pollen grains during
      their activation in vitro or on the stigma of a pistil. For this purpose the X
      ray microanalysis and spectrofluorometry were applied. We found that the relative
      content of potassium and chlorine in the microvolume of pollen grain decreases
      during its hydration and activation on stigma. Efflux of these ions was found
      both in vivo and in vitro. In model in vitro experiments anion channel inhibitor
      NPPB ((5-nitro-2-(3-phenylpropylamino) benzoic acid) in the concentration that
      was blocking pollen germination, reduced Cl- efflux; potassium channel inhibitor
      (tetraethylammonium chloride) partially reduced K+ efflux and lowered the percent
      of activated cells. Another blocker of potassium channels Ba2+ caused severe
      decrease in cell volume and blocked the activation. In general, the obtained data
      demonstrates that the initiation of pollen germination both in vivo and in vitro
      involves the activation of K+ and Cl- release. An important role in these
      processes is played by NPPB-, TEA- and Ba(2+)-sensitive plasmalemma ion channels.

PMID- 22650077
TI  - [Senescence and apoptosis of protoplasts from flax fibers: an ultrastructural
      analysis].
AB  - Plant fibers represent specialized cells that perform a mechanical function.
      Their development includes the following phases, typical for the most plant
      cells: anlage, extension growth, specialization, senescence, and apoptosis.
      Ultrastructural analysis of these cells has been carried out at the late phases
      of their development (senescence and apoptosis) using flax phloem fibers, a
      classical object for the analysis of sclerenchyma fiber formation. The results of
      the performed analysis show that flax fiber protoplasts remain viable until the
      end ofa vegetation season. The ultrastructural analysis of flax phloem fibers has
      not revealed any typical apoptosis manifestations. Gradual degradation of the
      cytoplasm starts during the active thickening of a secondary cell wall and
      manifests via the intensification of autolytic processes, causing a partial loss
      of cell content. The final stage represents the breaking of tonoplast integrity.
      The obtained data allow us to suppose that the apoptosis of flax fibers occurs
      during their senescence, and its program is similar to the cell death program
      realized in the xylem fibers of woody plants.

PMID- 22650078
TI  - [Genesis of cells of apical meristems and realization of gametophytic apomixis in
      flowering plants].
AB  - Based on our own and literature data on peculiarities of caryotypical
      variability, we concluded that gametophytic apomixis is naturally accompanied
      with phenomena of poly-, aneu-, and mixoploidy and that apomicts have genome
      instability manifesting at the level of meristematic somatic cells. In this
      connection, a hypothesis is substantiated that realization of this mode of seed
      reproduction in flowering plants is caused by modification of systems of cell
      cycle control, following after acts of hybridogenesis and/or polyploidization. It
      is concluded that instability of the seed reproduction system by gametophytic
      apomixis manifests not only at the stage of choice of a seed reproduction pathway
      (apomeiosis-euspory; apozygosis-zygosis) but also in all the cycles of
      reproduction of the cells of a germ line in plant ontogenesis.

PMID- 22650079
TI  - [Characteristics of the reparative regeneration of fins in the polypterid fish
      (Polypteridae, Actinopterygii)].
AB  - Epimorphic regeneration of fins was studied in different ray-finned fishes
      (Actinopterygii), but species representing the phylogenetically basal lineages of
      the taxon have remained outside the attention of researchers. Information on the
      regenerative abilities of these groups is important both for understanding the
      evolutionary origins of the epimorphic regeneration phenomenon and for assessing
      the universality of regenerative potencies in Actinopterygii. Addressing this
      problem, we studied for the first time fin regeneration in two members of the
      archaic family Polypteridae: the ropefish (Erpetoichthys calabaricus) and the
      Senegal bichir (Polypterus senegalus). Along with the ability to regenerate the
      bony rays of fins, widespread among Actinopterygii, polypterids show the ability
      to effectively regenerate the endoskeleton and musculature of their fins. This
      unusual feature allows us to suggest polypterids as new model organisms for the
      study of the mechanisms of vertebrate limb regeneration.

PMID- 22650080
TI  - [Chromatin folding in human spermatozoa. I. Dynamics of chromatin remodelling in
      differentiating human spermatids].
AB  - Changes in chromatin structure at different stages of differentiation of human
      spermatids were studied. It was shown that, in nuclei of early spermatids,
      chromatin is loosely packed and its structural element is an 8-nm fiber. This
      "elementary" fiber is predominant at the initial stages of differentiation; in
      the course of maturation, it is replaced by globular elements approximately 60 nm
      in diameter. In intermediate spermatids, these globules start to condense into
      fibrillar aggregates and reduce their diameter to 30-40 nm. At all stages of
      spermatid maturation, except the final stages, these globules are convergence
      centers for elementary fibers. This remodelling process is vectored and directed
      from the apical (acrosomal) to the basal pole of the nucleus. In mature
      spermatids, the elementary 8-nm fibers are almost absent and the major components
      are 40-nm fibrillar aggregates. The nuclei of mature spermatids are structurally
      identical with the nuclei of spermatozoa with the so-called "immature chromatin,"
      which are commonly found in a low proportion in sperm samples from healthy donors
      and may prevail over the normal cells in spermiogenetic disorders. The cause of
      this differentiation blockade remains unknown. Possibly, the formation of
      intermolecular bonds between protamines, which are required for the final stages
      of chromatin condensation, is blocked in a part of spermatids. The results of
      this study are discussed in comparison with the known models of nucleoprotamine
      chromatin organization in human spermatozoa.

PMID- 22650081
TI  - [Dynamics of fatty acid composition of total lipids during embryonic development
      of Atlantic salmon Salmo salar L].
AB  - Dynamics of fatty acid composition of total lipids was studied for freshwater
      salmon Salmo salar L. during its embryonic development from blastula (3 hours) up
      to hatching (108 days) as well as in unfertilized eggs. Stable amount of total
      and some saturated, monounsaturated and polyunsaturated fatty acids (PUFA) of
      total lipids was observed during embryonic development. Considerable changes in
      fatty acid composition were observed at the stage of prelarvae hatching, i.e.,
      significant decrease of (n-6) PUFA (18:2(n-6) and 20:4(n-6)) and (n-3) PUFA and
      increase of total and some saturated and monounsaturated fatty acids was
      registered. Change in saturation ratio of membrane lipids justifies the presence
      of the biochemical mechanism forwarded on regulation of cell membrane enzymes in
      accordance with the changes of internal physiological processes taking place in
      the organism and fluctuations of external environmental conditions or the
      preparation period (as reproduction). Data on peculiarities of transformation and
      utilization of fatty acids during salmon embryonic development may be used for
      understanding of their functional role in the developing organism as well as for
      assessing the quality of the caviar.

PMID- 22650082
TI  - Variety, the spice of clinical dentistry.

PMID- 22650083
TI  - Specialty recognition of oral medicine.

PMID- 22650084
TI  - "Dental lab registration: dentists leading the way".

PMID- 22650085
TI  - Focus on: CBCT technology.

PMID- 22650086
TI  - Get a "yes!" for nonsurgical periodontal treatment.

PMID- 22650087
TI  - Advances in local anesthetics: pH buffering and dissolved CO2.

PMID- 22650088
TI  - Shape of color: aesthetics from a physiologic perspective.

PMID- 22650089
TI  - Cosmetic nightmare! Composite success!

PMID- 22650090
TI  - Separated file removal.

PMID- 22650091
TI  - Making implant dentistry easier and less costly.

PMID- 22650092
TI  - A digital buffet.

PMID- 22650093
TI  - The direct composite bridge.

PMID- 22650094
TI  - Nanomicrohybrid composites make posterior placement easier.

PMID- 22650095
TI  - Treatment planning a bioesthetic case.

PMID- 22650096
TI  - [Risk of infection after placement of an extraventricular drainage catheter].
AB  - INTRODUCTION: The occurrence of infection after the placement of an
      extraventricular drainage (EVD) catheter can be a very serious problem in
      neurosurgery. OBJECTIVE: The aim of this study was to confirm that the use of
      special catheters with impregnated antibiotics decreased the percentage of
      infection. METHODS: The prospective study conducted at the Clinic of Neurosurgery
      in Nis in the period 2006-2009 is presented. Group 1 comprised of 43 patients in
      whom a commonly used system for EVD was applied. Group 2 comprised of 39 patients
      in whom the Rifampycin and Clindamycin impregnated EVD catheters were applied
      (Bactiseal catheters). RESULTS: In Group 1 infection occurred in nine patients,
      mainly caused by bacteria of Staphylococcus genus. In Group 2 only two patients
      developed infections caused by Acinetobacter. CONCLUSION: The use of Bactiseal
      EVD catheters considerably decreased the percentage of infection occurrence with
      prolonged EVD catheter drainage period.

PMID- 22650097
TI  - [Influence of initial visual field sensitivity on visual field loss progression
      in open angle glaucoma].
AB  - INTRODUCTION: It is important to know the risk factors for visual field defect
      progression in order to predict the future development of glaucoma. OBJECTIVE: To
      investigate the influence of visual field initial sensitivity on the rate of
      visual field progression. METHODS: A minimum of five visual fields were performed
      using computerized perimetry (Octopus) over a mean followup 4-year period (48.85
      +/- 17.84 months) in 64 persons (114 eyes) with primary open angle glaucoma. The
      rate of change of the whole central visual field and each of the seven regions of
      the field were measured by linear regression analysis of the mean sensitivity
      value versus time. Based on the slope of the regression line of visual field mean
      sensitivity over time the eyes were divided into two groups: the group with
      stable and the group with progressive visual field.The comparison of the mean
      sensitivity of the whole central visual field between the groups was performed
      using the Mann-Whitney U-test. The Spearman rang correlation coefficient and the
      Spearman probability p values were calculated to assess the mean sensitivity of
      the whole central visual field and of each visual field regions determined at the
      beginning of the study. RESULTS: The initial mean sensitivity of the whole
      central visual field was lower in the group with progressive visual field (16.62
      +/- 6.35 dB). Correlation between the initial mean sensitivity and the slope of
      the regression line was negative. The lowest mean sensitivity was in the group
      with progressive visual field in the upper temporal (13.73 +/- 7.35 dB), nasal
      (14.74 +/- 7.23 dB) and upper nasal (15.03 +/- 7.75 dB) regions. CONCLUSION: The
      lower mean sensitivity value of the visual field, especially in the nasal and
      upper nasal visual field regions, carries a greater risk for delayed progressive
      loss of the visual field in persons with glaucoma.

PMID- 22650098
TI  - [Prevalence of Chlamydia trachomatis in adults with chronic conjunctivitis in
      Nisava district].
AB  - INTRODUCTION: Chlamydia trachomatis causes many infections, including eye
      infections. They manifest as inclusion conjunctivitis and trachoma. The agent is
      transmitted by dirty hands, eyeliners, medical instruments and via swimming-pool
      water or, in neonates, by passage through an infected birth canal. Due to the
      nonspecific clinical features at the beginning of the infection and delayed
      application of symptomatic, anti-allergic and non-specific antibiotic therapy,
      Chlamydia aetiology is usually established only after laboratory diagnosis in the
      chronic stage of infection. OBJECTIVE: Determining the frequency of Chlamydia
      trachomatis antigen in conjunctival and genital samples of adult patients with
      chronic conjunctivitis in Nisava district. METHODS: Our retrospective study was
      carried out on 116 patients (63 female and 53 male) with clinical signs and
      symptoms of chronic conjunctivitis. Chlamydia trachomatis antigen was detected by
      a direct immunofluorescence test with labelled monoclonal antibodies. RESULTS:
      From a total of 116 examined patients in 37 patients Chlamydia trachomatis
      antigen was detected; 17 female and 20 male. Thirty-three of the patients had a
      bilateral infection and four unilateral. Among 24 patients who were also tested
      for Chlamydia trachomatis antigen collected by ocular and genital swabs, 19 had
      conjunctivitis associated with urethritis/vaginitis. CONCLUSION: The studied
      group of patients showed that the common cause of the chronic conjunctivitis were
      bacteria, but predominantly Chlamydia trachomatis. In most cases Chlamydia
      infection occurred bilaterally. The majority of patients had eye Chlamydia
      infection associated with genital Chlamydia infection. There was no statistically
      significant difference in the presence of the disease regarding gender.

PMID- 22650099
TI  - [Sudden hearing loss: our experiences in treatment with vasoactive and
      corticosteroid therapy].
AB  - INTRODUCTION: Sudden hearing loss is a clinical entity of ambiguously defined
      aetiology manifested by hearing loss of more than 30 dB on three contiguous
      frequencies occurring within 72 hours. The lack of standard therapy protocol led
      to the use of variety of different therapies, thus making difficult objective
      quantification of their effect. OBJECTIVE: The aim of the study was to present
      our experience in the treatment of sudden hearing loss with administration of
      vasoactive and corticosteroid therapy. METHODS: Our research included 59
      hospitally treated patients with a sudden hearing loss. During the period 1995
      2004, 37 patients were treated using vasoactive agents (xanthinol nicotinate and
      pentoxifylline), and from 2004-2009, 22 patients were treated using parenteral
      corticosteroids (dexamethasone). All patients had unilateral sensorineural
      hearing loss of different level at frequencies from 500-4000 Hz, while other
      diagnostic procedures (laboratory tests, internist and neurology examinations, X
      ray) were within normal limits. Evaluation of therapy effect was done by follow
      up of hearing threshold changes and subjective complaints. RESULTS: The results
      showed that full recovery was achieved in patients with a mild and not fully
      severe hearing loss, with the majority of those (73%) under corticosteroid
      treatment. In these patients recovery was also achieved more rapidly. A partial
      recovery of hearing was detected in patients with hearing loss of more than 80
      dB, and mostly in patients treated with corticosteroids. CONCLUSION: Although
      statistical evaluation does not indicate significant differences between the
      application of vasoactive drugs or corticosteroids, clinical findings support
      advantages of corticosteroid therapy. Treatment of hearing loss, although
      controversial, requires change of some up-to-now used agents. Advantages should
      go in favour of contricosteroids.

PMID- 22650100
TI  - [Early detection possibilities of obstructive sleep apnoea syndrome].
AB  - INTRODUCTION: Obstructive sleep apnoea (OSA) syndrome represents a significant
      medical problem due to numerous consequences that may follow it. OBJECTIVE: The
      aim of the study was to analyze morphology of the maxilla in children with mouth
      breathing, and to assess possible characteristics in persons with marked clinical
      features of OSA. METHODS: The sample comprised of 60 examinees aged from 8-10
      years, all mouth-breathers. The following X-ray cephalometric parameters were
      measured: angle of maxillary pragmatism, cranial base angle, angle between the
      palatal plane and the anterior cranial base, maxillary length, distance from the
      most prominent labial surface of the maxillary central incisor to NA line, angle
      between the axis of the upper maxillary incisor and NA line. Following parameters
      were obtained from the casts: anterior and posterior width of the maxillary arch,
      height of the maxillary arch, index of the palatal height, as well as the apical
      base length. Assessed values were then compared to the corresponding norms.
      RESULTS: Compared to the corresponding norms, statistically significant lower
      values were determined for the following parameters of the sample: SpP/SN, AW,
      PW, AB. CONCLUSION: Analysis of the morphological characteristics of the maxilla
      in mouth breathing children showed characteristics also present in persons with
      marked clinical features of OSA syndrome, such as a narrow maxilla, insufficient
      apical base length, as well as the reduced angle of the palatal plane angle to
      the anterior cranial base. All these suggest a possible increased risk of
      developing OSA syndrome in children's later age.

PMID- 22650101
TI  - [Simvastatin influence on carotid atherosclerotic disease regression].
AB  - INTRODUCTION: The measurement of intima-media thickness (IMT) of carotid arteries
      has emerged as the method of choice for determining the anatomic extent of
      atherosclerosis and assessing cardiovascular progression. Statins are used in the
      primary and secondary prevention of cardiovascular and cerebrovascular disorders
      so as to reduce morbidity and mortality. OBJECTIVE: To evaluate the effects of
      treatment with simvastatin in patients with elevated cholesterol levels and
      increased values of carotid arteries IMT. METHODS: The study of 275 patients (155
      male and 115 female, aged 37-79 years, mean 60.86 years) was performed from
      January 2008 - January 2010 at the Vascular and Endovascular Surgery Clinic of
      the Clinical Centre of Serbia. All patients were treated with simvastatin
      administered once a day for 6 months. RESULTS: Simvastatin treatment resulted in
      a statistically signuficant decrease of the IMT thickness of the right common
      carotid artery. There was no statistically significant reduction in the IMT of
      the left common carotid artery as well as in the IMT of the right and left
      internal carotid arteries. CONCLUSION: Long-term simvastatin treatment results in
      the regression or slowing down atherosclerosis in symptomatic, as well as in
      asymptomatic patients with a lower grade of carotid stenosis (IMT below 2.5 mm).

PMID- 22650102
TI  - [Endoscopic treatment of gastric and duodenal angiodysplasias by elastic rings
      ligation].
AB  - INTRODUCTION: The most frequently applied methods of endoscopic treatment of
      angiodysplasias, such as argon plasma coagulation, multipolar coagulation and
      heater probe, proved to be effective with certain shortcomings and the
      possibility of complications. There are very scarce data in the literature about
      the treatment of angiodysplasias with endoscopic ligature. OBJECTIVE: The aim of
      the study was to examine the efficacy and safety of endoscopic treatment of
      gastric and duodenal angiodysplasias by ligation with elastic rings. METHODS: In
      12 patients (10 male and 2 female, mean age 65.9 years) the endoscopic ligation
      of gastric and duodenal angiodysplasias was applied. Eight patients (66.6%) had
      solitary angiodysplasias in the stomach, two patients (16.6%) had solitary
      angiodysplasias in the descending part of the duodenum and two patients (16.6%)
      had multiple angiodysplasias in the stomach and duodenum.Two patients (16.6%) had
      active bleeding from angiodysplasias, while 10 patients (83.3%) had recent
      bleeding. We used the Cook Endoscopy system with 4 or 6 elastic rings for
      endoscopic ligation of angiodysplasias. Patients were under follow-up after 2-3
      days, 30 days and then every 6 months following the endoscopic ligation of
      angiodysplasias. RESULTS: Active bleeding from angiodysplasias was stopped in two
      patients (100%) by endoscopic ligation with elastic rings. The average number of
      applied ligation sessions in our 12 patients was 1.6, with an average of 1.8
      ligatures per session. There were no complications after ligation of
      angiodysplasias. Recurrence of bleeding occurred in one patient (8.3%) with
      multiple gastric and duodenal angiodysplasias.The average period of follow-up of
      patients was 22.8 +/- 17.6 months. CONCLUSION: Endoscopic ligation with elastic
      rings can be effective and safe for treatment especially of solitary gastric and
      duodenal angiodysplasias.

PMID- 22650103
TI  - [Evaluation of methods for rapid microalbuminuria screening in kidney diseased
      patients].
AB  - INTRODUCTION: One of the criteria for chronic kidney disease detection is
      determination of microalbuminuria. OBJECTIVE: This analysis was performed to
      evaluate accuracy of three useful methods for microalbuminuria detection in 24h
      urine collection and in the morning urine specimen calculated from urine albumin
      creatinine ratio, or with a dipstick in patients with different kidney diseases
      or kidney function. METHODS: Microalbuminuria was detected in 74 patients
      referred to the Outpatient Nephrology Department for kidney function
      determination or regular nephrology checking. Albumin concentration determined
      using immunonephelometry was lower than 300 mg/day. Discriminates cutoff values
      for spot urine test strip and albumin creatinin ratio in predicting 24 h
      protein'threshold' excretion were determined using ROC analysis. RESULTS: Mean
      value of 24 h microalbuminuria was 80.3 mg/24 h, and value >30 mg/24 h was
      present in 71.8% of patient. Correlation coefficients between dipstick
      microalbuminuria or albumin/creatinine ratio in a spot urine specimen and 24 h
      microalbuminuria were 0.709 and 0.598 (p<0.0001). For pathological value of 24 h
      microalbuminuria >30 mg/24 h, the coresponding dipstick microalbuminuria value
      was > or = 20 mg/L (AUC 0.849, specificity 95%, positive predictive value 97.3%),
      and > or = 3.55 mg albumin/mmol creatinine ratio (AUC 0.914, specificity 90% and
      positive predictive value 95.5%). No difference was found between dipstick
      mikroalbuminuria and albumin/creatinine ratio value. In addition,
      albumin/creatinine ratio value from 24 h urine was similar to the value obtained
      from the spot urine sample. CONCLUSION: Obtained results indicated that
      albuminuria could be determined accurately in spot urine either with the Micral
      test strip or with albumin creatinine ratio.

PMID- 22650104
TI  - Antibiotic resistance of uropathogens in newborns and young children with acute
      pyelonephritis.
AB  - INTRODUCTION: Urinary tract infection is common in childhood. Depending on the
      localization of the infection, severity of its clinical presentation and possible
      acute and long-term complications, it may be described as either acute cystitis
      or acute pyelonephritis. OBJECTIVE: The aim of this study was to assess the
      resistance patterns of uropathogens during the last 5 years in newborns and young
      children with acute pyelonephritis. METHODS: Uropathogens resistance to commonly
      usable anti-microbial agents (ampicillin, a combination of sulphamethoxasole and
      trimethoprim, cephalexin, ceftriaxone, cefotaxime, ceftazidime, gentamycin,
      amikacin, ciprofloxacin, imipenem and nalidixic acid) was retrospectively studied
      in newborns and young children treated during early (2005-2007) and late (2008
      2009) study periods. Anti-bacterial susceptibility testing of the urine isolates
      was performed by the standard disc diffusion method. RESULTS: 117 newborns and
      294 children aged 9.3 +/- 0.7 months were treated during early (n=136) or late
      (n=275) study period due to the first episode of acute pyelonephritis.
      Escherichia coli was the most common bacterial pathogen (85.5%). Compared to
      children older than one month, newborns had higher degree of antibacterial
      resistance to 2nd and 3rd generation cephalosporins, aminoglycosides, and
      nalidixic acid during early, and to ceftazidime, aminoglycosides and nalidixic
      acid during late study period. Also, multidrug resistance was more common in
      newborns during the early study period. CONCLUSION: Newborns had higher rate of
      antibacterial resistance than young children.The progressive increase of anti
      microbial resistance in children with acute pyelonephritis is of great concern.

PMID- 22650105
TI  - [Urinary tract nosocomial infections at the Clinical Centre in Kragujevac].
AB  - INTRODUCTION: Urinary tract infections are the most frequent hospital infections
      and account for about 40% of total hospital infections. The main risk factor for
      their development is the use of catheters. OBJECTIVE: Assessment of basic
      epidemiological and etiological characteristics of nosocomial urinary tract
      infections (NUTIs) and investigation of differences in risk factors among the
      patients with NUTIs with and without the urinary catheter. METHODS: The study
      comprised patients treated in chosen units/ of the Clinical Center in Kragujevac,
      in whom NUTI was registered during 2009. Differences in risk factors for NUTIs
      between the catheterized and uncatheterized patients were tested by the logistic
      regression analysis. RESULTS: NUTIs was registered in 162 patients whose average
      age was 66.2 +/- 13.5 years with approximately equal gender participation (51.2%
      men and 48.8% women). Almost three quarters of the patients with NUITs had
      indwelling urinary catheter, 12.0 +/- 7.7 days on average (from 1 to 39 days). In
      the patients with urinary catheter, the risk for NUITs was significantly
      positively associated with emergency admission to hospital treatment (p=0.0185).
      The uncatheterized patients had a significant frequency of malignant tumours
      comparing to the patients with a urinary catheter (p=0.039). The compared groups
      did not differ in other risk factors. The most frequently isolated microbial
      agents was Klebsiella spp (37.3%), then Pseudomonas aeruginosa (14.1%) and
      Proteus mirabilis (11.9%). Most of the bacteria showed a great level of
      resistance to frequently used antibacterial drugs, even up to 100%. CONCLUSION:
      It is necessary to define national recommendations for the prevention and control
      of NUTIs in the future.

PMID- 22650106
TI  - [Clinical characteristics and disease course in children with haemophagocytic
      lymphohistiocytosis treated at the University Children's Hospital in Belgrade].
AB  - INTRODUCTION: Haemophagocytic lymphohistiocytosis (HLH) is a disorder
      characterised by long-standing fever, splenomegaly and bicytopoenia or
      pancytopoenia. Lymphadenopathy, jaundice and neurological symptoms mayalsooccur.
      HLH may ensue in various forms of innate or acquired immunodeficiency with
      impaired cytotoxic lymphocyte function resulting in excessive macrophage
      activation. OBJECTIVE: To describe and analyse clinical characteristics of
      patients treated for HLH at the University Children's Hospital of Belgrade from
      August 2000 to August 2010. METHODS: Retrospective analysis of medical records.
      RESULTS: Diagnosis of HLH was established in 13 children (five boys and eight
      girls) aged from one month to 14 years. In six children HLH was secondary (to
      visceral leishmaniasis in two, Ebstein-Barr virus infection in one, Langerhans'
      cell histiocytosis in one and systemic juvenile rheumatoid arthritis in two). Of
      the remaining seven patients, genes for perforin and syntaxin 11 were examined in
      two and no mutations were found. Of the remaining seven patients, genes encoding
      perforin and syntaxin 11 were analyzed in two, but no mutations were found. All
      children had fever, splenomegaly, cytopoenias, hyperferritinaemia and
      hypertriglyceridaemia, but haemophagocytosis was seen in only six (46.1%). Six
      children were cured (four with secondary HLH and two with primary HLH).Two
      children are undergoing treatment, while five succumbed (three before treatment
      could be administered and two due to complications). In four of the six cured
      children, HLH arose in the first year of life. Cure rate in those who underwent
      haematopoietic stem cell transplantation was 2/3. CONCLUSION: Results underscore
      the importance of timely diagnosis and treatment of HLH, warranting that in all
      children with fever, splenomegaly and/or cytopoenias, with or without
      haemophagocytosis, HLH be actively sought.

PMID- 22650107
TI  - [Near-hanging with outliving period: pathoforensic aspects].
AB  - INTRODUCTION: Hanging usually ends in death, and about 80% of victims are found
      dead at the scene of the hanging. However, sometimes the hanging victims overlive
      for some time, and sometimes even survive the hanging. OBJECTIVE: The aim was to
      determine the causes of death in near-hanging cases, in people who have been
      outliving hanging for some time, to explain the pathophysiological mechanisms
      leading to death, and to identify prognostic factors for this outcome. METHODS:
      Retrospective autopsy study was performed for a twelve-year period. There were
      only seven cases of near hanging.The sample was analyzed according to gender,
      age, circumstances of death, and autopsy findings of all observed subjects. The
      relevant data were collected from autopsy records, police reports and
      heteroanamnestic interviews. RESULTS: The sample consisted of five men and two
      women, average age 48.3 +/- 19.9 years (29-81 years). The average outliving
      period was 3.8 +/- 2.6 days (from 7 hours to 7 days). Six people were admitted to
      hospital in the state of deep coma. In six cases cardiopulmonary arrest occurred
      after the hanging attempt and all were reanimated for a shorter or longer time
      until admission at hospital. CONCLUSION: Survival after attempted suicide by
      hanging occurs extremely rarely. In all the cases, the immediate cause of death
      after attempted hanging was ischemic brain injury, with a significant and
      pronounced oedema. In all the cases observed, regardless of the presence or
      absence of injuries of soft and hard structures of the neck, there was a ligature
      mark on the neck skin. Acute hemorrhagic gastritis with melaena was present in a
      significant number of reported cases of near-hanging.

PMID- 22650108
TI  - [Significance of perfectionism in understanding different forms of insomnia].
AB  - INTRODUCTION: Studies consistently show a connection between perfectionism as a
      multidimensional construct with various psychological and psychopathological
      states and characteristics. However, studies that analyze the connection between
      this concept and sleep disturbances, especially modalities of insomnia, are rare.
      OBJECTIVE: The aim of this study was to examine whether dimensions of
      perfectionism can explain different forms of insomnia; difficulties initiating
      sleep (insomnia early), difficulties during the sleep (insomnia middle), waking
      in early hours of the morning (insomnia late) and dissatisfaction with sleep
      quality (subjective insomnia). METHODS: The sample consisted of 254 students of
      the School of Medicine in Belgrade. Predictive significance of nine perfectionism
      dimensions, measured by Frost's and Hewitt's and Flett's scales of multi
      dimensional perfectionism, related to four modalities of insomnia, measured by a
      structured questionnaire, was analyzed by multiple linear regression method.
      RESULTS: Perfectionism dimensions are significant predictors of each of the
      tested forms of insomnia. Doubt about actions significantly predicts initial
      insomnia; to other-oriented perfectionism in the negative pole and socially
      prescribed perfectionism underlie the difficulties during the sleep, while
      organization and parental criticism underlie late insomnia. Significant
      predictors of subjective insomnia are personal standards and organization and to
      other-oriented perfectionism on the negative pole. Three of nine analyzed
      dimensions were not confirmed as significant; concern over mistakes, parental
      expectations and self-oriented perfectionism. CONCLUSION: Various aspects of
      perfectionism can be considered as a vulnerability factor for understanding some
      forms of insomnia. Out of all forms of insomnia tested, perfectionism as the
      personality trait proved to be the most significant for understanding subjective
      insomnia.

PMID- 22650109
TI  - Asymptomatic perforation of large bowel and urinary bladder as a complication of
      ventriculoperitoneal shunt: report of two cases.
AB  - INTRODUCTION: Insertion of a ventriculoperitoneal (VP) shunt, the method of
      choice in the treatment of hydrocephalus, is often followed by various mechanical
      and/or infective complications. We present two children with asymptomatic
      perforation of the large bowel and urinary bladder, relatively rare and
      potentially severe complications of this surgical procedure. OUTLINE OF CASES: In
      both patients a VP shunt was implanted in the first month after birth; in a boy
      due to congenital hydrocephalus and in a girl due to the consequences of
      intracranial haemorrhage. Immediately after surgery, as well as during the
      further course, in both children growth and development were optimal and without
      any signs of infection or VP shunt malfunction. In the boy at age 6 months and in
      the girl at age 4 years, without any signs of complications, mothers noted the
      prominence of the VP shunt tip from the anus in the first case and from the
      urethral orifice in the second one. The VP shunts were immediately changed, so
      that both complications were resolved without any consequences. CONCLUSION:
      Insertion of a VP shunt represents the most frequent method of choice of the
      surgical treatment of hydrocephalus, but also potentially a highly risky
      procedure followed by various complications about which parents should be
      informed when patients are children. Owing to adequate approach in the follow-up
      of children with implanted VP shunt, large bowel and urinary bladder perforation,
      examples of severe and potentially fatal complications of this surgical
      intervention, could be disclosed on time and adequately resolved.

PMID- 22650110
TI  - [Pendular stromal tumour of the stomach with dominant PDGFRA immunoexpression:
      case report and short literature review].
AB  - INTRODUCTION: Gastrointestinal stromal tumours are most frequent mesenchimal
      tumours of the gastrointestinal tract that originate from Cajal's interstitial
      cells that are most frequently CD-117 positive. Stromal tumours of the stomach
      are the most frequent mesenchimal tumours of the gastrointestinal tract. Such
      tumours are usually sessile, but rarely pendular when they can be easily removed
      with a limited local excision of the stomach wall around the pedicle. Major
      stomach resections are rarely necessary. CASE OUTLINE: In a 54-year-old woman
      with abdominal pain and fever of unknown aetiology, a large spherical mobile and
      almost painless mass was found within the upper right abdomen. US and CT showed a
      mainly cystic, partly solid tumour, of 15.5x12.5 cm in diameters. Laboratory data
      including tumour markers were within normal limits. At operation a mobile and
      free tumour of the stomach attached to the anterior wall with a 2.5 cm pedicle
      was found and easily excised. Abdominal mucosa was normal. There was no liver
      metastasis or peritoneal dissemination. Hystology and imunohistochemistry showed
      a rare sclerosing sincitial subtype of stromal tumour with imunophenotype
      heterogenicity with a dominant PDGFRA and rare CD-117 immunoexpression. The
      postoperative recovery was uneventful. The patient was symptom-free with no sign
      of recurrence after a year and a half. CONCLUSION: A rare subtype of histological
      highly malignant stromal tumour of the stomach, macroscopically of pendular type,
      that was easily excised, was presented which so far showed a favourable evolution
      with no signs of recurrence.

PMID- 22650111
TI  - Laparoscopic body-tail pancreatic resection for insulinoma.
AB  - INTRODUCTION: Insulinomas are the most common endocrine tumours of the pancreas.
      They are more frequent in females, and they are commonly less than 2 cm in
      diameter. If conservative treatment of typical clinical symptoms fails, detailed
      diagnostic procedures are necessary and surgical treatment is indicated.The aim
      of this report was to emphasize the need of pancreatic resection when insulinoma
      is poorly visualized during surgery and when it is not possible to perform
      intraoperative ultrasonography. CASE OUTLINE: A 27-year-old female patient
      suffered from hypoglycaemic episodes during physical efforts and fasting periods.
      After examination, diagnostic procedures and preoperative preparation,
      laparoscopic surgery was performed. The tumour was less than 10 mm in diameter,
      and it could not be visualized during laparoscopic exploration. The body and the
      tail of the pancreas were mobilized using ultrasound scissors and the resection
      was performed by two Endo GIA staplers. The surgical specimen was removed in an
      endo-bag. The postoperative course was without complications and the glycemic
      level was normalized. Macroscopic examination of the resected specimen showed a
      solitary, poorly demarcated, dark grey lesion, 0.8 cm in diameter, with a solid
      consistence in comparison with the surrounding gland tissue. Histological
      examination showed a poorly demarcated, subcapsular tissue in this area,
      consisting of uniform, irregular, cubic and short cylindrical cells, organized in
      clusters with pseudoglandular and "zellballen" formations. CONCLUSION: In case
      when the insulinoma is so small in size that it cannot be visualized during
      operation, pancreas resection is a surgical procedure of choice. Laparoscopic
      surgery is preferred because of less postoperative complications and faster
      recovery.

PMID- 22650112
TI  - Distal ileal endometriosis as a cause of ileus: a case report.
AB  - INTRODUCTION: Endometriosis is a benign condition affecting females of
      reproductive age. Although intestinal endometriosis is common, it is rarely
      manifested as an acute bowel obstruction secondary to ileal endometriosis.
      Enteric endometriosis should be considered as a differential diagnosis when
      assessing females of reproductive age with acute small bowel obstruction. CASE
      OUTLINE: A 41-year-old woman presented with symptoms and signs of an acute small
      bowel obstruction requiring emergency surgery. A small bowel resection was
      performed with end-to-end anastomosis. Histological examination demonstrated
      endometriosis with fibrosis and stricture of the ileal segment. This case is
      important to report as it highlights the diagnostic difficulty this particular
      condition pre sents to an emergency surgeon. CONCLUSION: In the differential
      diagnosis, endometriosis should be taken into consideration when assessing
      females of reproductive age who present with abdominal pain and small bowel
      obstruction.

PMID- 22650113
TI  - [Unusual case of successful hand replantation with bad functional outcome: a case
      report].
AB  - INTRODUCTION: Traumatic hand amputation is a very severe and rare injury.
      Replantation and revascularization surgery requires the existence of specialized
      centres and well-educated teams of microsurgeons. In places where there are no
      such specialized centres for this kind of surgery, traumatic hand amputation is a
      major concern and quite a challenge, and a successfully performed replantation is
      a great accomplishment. CASE OUTLINE: We report a case of a successfully survived
      replanted hand in a 35-year-old male patient with unfortunately bad end result of
      the treatment. The patient with the amputated left hand (disarticulation) had a
      surgery 4 hours after injury. The urgent surgical procedure required a
      debridement, the excision of the first row of the carpal bones, external fixation
      of the wrist, vascular anastomoses, nerve repair, tenorrhaphy, skin sutures and
      decompression skin incisions.The successful operation did not have a successful
      post-operative course due to the patient's psychiatric problems and lack of
      rehabilitation at the psychiatric institution where the treatment was continued.
      CONCLUSION: Successful surgical performance can unfortunately be ruined due to
      inadequate further treatment course or the wrong selection for such a demanding
      surgery. The survival of the amputated hand can be achieved surgically, but
      achieving refunctioning does not always depend on surgery. It also depends on the
      very patient, his motivation, rehabilitation, as well as on the proper selection
      for such a demanding and complex surgical procedure.

PMID- 22650114
TI  - Immediate allergic reaction to methylprednisolone with tolerance of other
      corticosteroids.
AB  - INTRODUCTION: In spite of the wide usage of corticosteroids for the treatment of
      a plethora of diseases, sometimes they can induce immediate hypersensitivity
      reactions, which are however uncommon. CASE OUTLINE: We report a case of
      immediate allergic reaction induced by intravenous methylprednisolone given
      before operation for surgical repair of an arm contracture as a sequel of burns,
      which the child had tolerated a month before. Six weeks later the patient
      repeated the anaphylactic reaction during skin testing to methylprednisolone. In
      addition, basophile activation test with methylprednisolone (BAT) was positive.
      CONCLUSION: This case report describes a patient who experienced intraoperative
      anaphylaxis and anaphylactic reaction induced by skin testing. This is the first
      report on induction of both anaphylactic reactions by methylprednisolone in the
      same child. Clinical findings, positive BAT and positive skin tests with
      methylprednisolone imply that the child developed type-I hypersensitivity. The
      lack of crossreactivity with other corticosteroids emphasizes that the reactions
      were caused by the steroid molecule.

PMID- 22650116
TI  - Cystic fibrosis.
AB  - Cystic fibrosis (CF) is a multisystemic autosomal recessive disease caused by a
      defect in the expression of CFTR protein, i.e. chloride channel present in the
      apical membrane of respiratory, digestive, reproductive and sweat glands
      epithelium. It primarily occurs in the Caucasians, while being considerably or
      excep tionally rare in persons of other races. Absence, deficit or structural and
      functional abnormalities of CFTR protein lead to mucosal hyperconcentration in
      the respiratory, digestive and reproductive systems and malabsorption of chloride
      and sodium in the sweat glands. Thus, the clinical features of patients' with CF
      are predominated by respiratory, digestive and reproductive disorders, as well as
      the tendency to dehydration in the condition of increased sweating. Beside
      genotype variations, the degree of disease manifestation is also essentially
      influenced by various exogenous factors, such as the frequency and severity of
      respiratory infections, the level of aero-pollution, quality of
      immunoprophylaxis, patients' nutritional condition and other. Chloride
      concentration of over 60 mmol/L in sweat, a high level of immunoreactive
      chymotrypsinogen in blood and the verification of homozygous mutation of CFTR
      gene are the basic methods in the diagnostics of the disease. CF belongs to the
      group of severe and complex chronic diseases, and therefore requires
      multidisciplinary therapeutic approach. Owing to the improvement of healthcare
      provision, most patients with CF now survive into adulthood. In addition, their
      quality of life is also considerably improved.

PMID- 22650115
TI  - Autism and autistic spectrum disorders in the context of new DSM-V
      classification, and clinical and epidemiological data.
AB  - Autism is one of disorders from the autism spectrum, besides Asperger syndrome,
      atypical autism and pervasive developmental disorder not otherwise specified.
      They are classified as mental disorders as being manifested by a wide range of
      cognitive, emotional and neurobehavioural abnormalities. Key categorical
      characteristics of the disorder are clear impairments of the development of the
      child's socialisation, understanding and production of verbal and non-verbal
      communication and restricted and repetitive patterns of behaviour. Demarcation
      boundaries are not clear, neither within the very group of the disorders from the
      autistic spectrum, nor with respect to the autistic behavioural features in the
      general population. For this reason, the term spectrum points out the
      significance of the dimensional assessment of autistic disorders, which will most
      likely be the basis of the new diagnostic classification of the disorders
      belonging to the current group of pervasive developmental disorders in the new
      DSM-V classification. The understanding, as well as the prevalence of the
      autistic spectrum disorders has changed drastically in the last four decades.
      From the previous 4 per 10,000 people, today's prevalence estimates range from
      0.6 to around 1%, and the increase of prevalence cannot be explained solely by
      better recognition on the part of experts and parents or by wider diagnostic
      criteria. The general conclusion is that the autistic spectrum disorders are no
      longer rare conditions and that the approach aimed at acknowledging the warning
      that this is an urgent public health problem is completely justified.

PMID- 22650117
TI  - [Developmental conditions of medicine and spiritual culture at the time of grand
      Prince Stefan Nemanja].
AB  - Medieval medicine and pharmacy were the subjects of numerous researches. The
      enviable level of health culture and social care of the diseased and debilitated
      people of the Serbian medieval state was far advanced for the time. However,
      there are scarce written records of the conditions. The purpose of this paper is
      to point out the conditions which enabled the foundation of the first Serbian
      hospitals, development of scientific medicine and spiritual culture in medieval
      Serbian lands. Favourable conditions for the development of medieval medicine are
      linked with the arrival of the Nemanjic dynasty to the throne of the Serbian
      medieval state, i.e. Stefan Nemanja, and later with the life and work of his son
      Prince Rastko Nemanjic - Saint Sava. The wide field of activity of the Grand
      Prince Stefan Nemanja included the creation of stable and independent state ("the
      unifier of all Serbian lands") with a significant and shrewd political activity
      (vassal to Byzantine Emperor Manuel Comnenus, participation in great alliances
      against Byzantium), building of churches, defender of the Orthodox Christianity,
      foundation of the first Serbian hospital outside of borders of Serbian state in
      Hilandar monastery, social care about people and cultivating literary activity.

PMID- 22650118
TI  - [Impacts of acupuncture and moxibustion on outcome indeices of depression
      patients' subjective reports].
AB  - OBJECTIVE: To assess the clinical efficacy of acupuncture and moxibustion on
      depression in view of the outcome indicators of the patient subjective reports.
      METHODS: One hundred and sixty-three cases of depression being in compliance with
      the inclusive standards were randomized into a soothing-liver and regulating-mind
      group, an acupoint-shallow-puncturing group and a non-acupoint-shallow-puncturing
      group. In the soothing-liver and regulating-mind group, the conventional
      acupuncture was applied to the four-gate points [Hegu (LI 4) and Taichong (LR
      3)], Baihui (GV 20) and Yintang (EX-HN 3), the direct moxibustion with moxa cone
      was applied to the four-flower points [Geshu (BL 17), Danshu (BL 19)]. Finally,
      the intradermal needling was used at Xinshu (BL 15) and Ganshu (BL 18). In the
      acupoint-shallow-puncturing group, the acupoints selected were same as those in
      the soothing-liver and regulating-mind group. But the needle insertion was
      shallower and the time of moxibustion was shorter. In the non-acupoint-shallow
      puncturing group, the spots that were 10 mm lateral to those acupoints in the
      soothing-liver and regulating-mind group were selected. The operation was same as
      that in the acupoint-shallow-puncturing group. The treatment was given twice a
      week in three groups. Totally, 12 weeks of treatment were required. The score of
      symptom checklist 90 (SCL-90), the self-report symptom inventory was observed
      before treatment, 1 month and 3 months after treatment separately so as to assess
      the corresponding short-term, mid-term and long-term efficacies of the program of
      acupuncture and moxibustion for soothing the liver and regulating the mind.
      RESULTS: In each time-point after treatment, for the scores of somatization,
      obsessive-compulsive symptom, interpersonal sensitivity, depression, anxiety,
      hostility, paranoid ideation, psychoticism and the other 8 dimensionalities, in
      comparison between the soothing-liver and regulating-mind group and the non
      acupoint-shallow-puncturing group, the differences were significant statistically
      (all P < 0.05). For the scores of depression, anxiety and hostility, in
      comparison between the soothing-liver and regulating-mind group and the acupoint
      shallow-puncturing group, the differences were significant statistically (all P <
      0.05). CONCLUSION: Acupuncture and moxibustion can improve the scores of SCL-90
      scale for the patients with depression. The outcome indicators of the patient
      subjective reports can accurately assess the clinical efficacy.

PMID- 22650119
TI  - [Observation on therapeutic effect of type II early diabetic nephropathies
      intervened by acupoint thread embedding].
AB  - OBJECTIVE: To observe the therapeutic effect of type II early diabetic
      nephropathies intervened by acupoint thread embedding for strengthening spleen
      and benefiting kidney. METHODS: Sixty cases of type II early diabetic
      nephropathies were randomly divided into an acupoint thread embedding group and a
      routine therapy group, 30 cases in each group. In routine therapy group, western
      medicine routine therapy was applied to control blood sugar, blood pressure and
      blood lipid. In acupoint thread embedding group, besides the western medicine
      routine therapy, thread embedding intervention was given at Pishu (BL 20),
      Zusanli (ST 36), Shenshu (BL 23) and Yishu (Extra) on both sides as main
      acupints, and the treatment course was 3 months. Urinary micro-albumin excretion
      (UAER), total score of TCM syndrome and monitor control indices (blood sugar,
      blood pressure, blood lipid, urea nitrogen and serum creatinine) in both groups
      were observed before and after treatment, and the therapeutic effects in both
      groups were compared. RESULTS: After treatment, the indices of UAER and total
      score of TCM syndrome were all reduced (P < 0.001, P < 0.01); the reduction in
      acupoint thread embedding group was more obvious (P < 0.01, P < 0.05); the total
      effective rate in acupoint thread embedding group was 76.7% (23/30), superior to
      that of 63.3% (19/30) in routine therapy group (P < 0.05). The blood sugar, blood
      pressure and blood lipid in both groups were remarkably improved (all P < 0.001)
      after treatment; the urea nitrogen and creatinine had no notable variation.
      CONCLUSION: Acupoint thread embedding combined with western medicine routine
      therapy can not only reduce the urinary micro-albumin excretion of type II early
      diabetic nephropathies, but also improve the Chinese medicine symptoms and the
      therapeutic effect is superior to that of simple western medicine routine
      therapy.

PMID- 22650120
TI  - [Acupuncture combined with auricular point sticking for 20 cases of white lesions
      of vulva].

PMID- 22650122
TI  - [Efficacy observation on supraspinal ligament injury in deficiency syndrome
      treated with acupuncture at Dazhong (KI 4) only].
AB  - OBJECTIVE: To compare the efficacy difference on the treatment of supraspinal
      ligament injury in deficiency syndrome between only-puncturing at Dazhong (KI 4)
      and routine acupuncture therapy and then explore an optimum process. METHODS: One
      hundred and twenty-six cases were randomly divided into a Dazhong group (63
      cases) and a routine acupuncture group (63 cases). Based on the same treatment
      including TDP irradiation, cupping at Shenshu (BL 23), Dachangshu (BL 25),
      Mingmen (GV 4), Yaoyangguan (GV 3) and Ashi points, the patients in the Dazhong
      group received only-puncturing Dazhong (KI 4) with respiratory reinforcing method
      once daily or every other day, three times of which made a course of the
      treatment, with on interval of one day or without between different courses. For
      the routine acupuncture group, the same reinforcing method was applied at shenshu
      (BL 23) pointect, and the other requirements such as courses were also the same.
      RESULTS: The cured and markedly effective rate was 88.9% (56/63) in the Dazhong
      group, which was significantly superior to that of 54.0% (34/63) in the routine
      acupuncture group (P < 0.01). Compared before and after the treatment, the score
      of Numerical Rating Scale (NRS) and the clinical symptom score of the two groups
      were significantly decreased (all PF < 0.01). Compared between the two groups,
      there were significant differences in NRS and clinical symptom score the Dazhong
      group was better than the routine acupuncture group (both P < 0.01). CONCLUSION:
      The only-puncturing Dazhong (KI 4) method combined with cupping and TDP
      irradiation are simple and effective for supraspinal ligament injury in
      deficiency syndrome.

PMID- 22650121
TI  - [Comparison of the clinical therapeutic effects between electroacupuncture and
      warming needle moxibustion for knee osteoarthritis of kidney deficiency and
      marrow insufficiency pattern/syndrome].
AB  - OBJECTIVE: To explore the actions of electroacupuncture (EA) and the warming
      needle moxibustion on knee osteoarthritis (KOA) of kidney deficiency and marrow
      insufficiency pattern/syndrome and compare the clinical effects between these two
      therapies. METHODS: Seventy-four cases of KOA were randomly divided into an
      electroacupuncture (EA) group and a warming needle moxibustion (WNM) group, 37
      cases in each one. The acupoints were Dubi (ST 35), Neixiyan (EX-LE 4), Xuehai
      (SP 10), Zusanli (ST 36), Yanglingquan (GB 34), etc. In EA group, electric
      stimulation was given, 5 Hz, continuous wave. In the WNM group, warm needling
      technique was applied, 2 moxa cones on each acupoint in each time, three
      treatments a week. Totally, 4 weeks of treatment were required. The indicaices
      such as WOMAC score, illness severity index and systematic efficacy were adopted
      to evaluate the efficacy before treatment, 1 session and 2 sessions after
      treatment separately. RESULTS: The treatment in either group achieved the
      effectiveness. The cured and markedly effective rate was 64.7% (22/34) in EA
      group and was 40.0% (14/35) in WNM group, presenting statistically significant
      difference in comparison (P < 0.05). But the total effective rate did not
      indicate significance (P > 0.05). In EA group, the releasing effect of joint pain
      was obvious (P < 0.01). In the WNM group, the treatment was more advantageous at
      relieving joint stiffness (P < 0.01). There was no difference in the mean
      curative time between two groups (P > 0.05). CONCLUSION: Electroacupuncture and
      the warming needle moxibustion have their own advantages in the treatment of KOA
      of kidney deficiency and marrow insufficiency pattern/syndrome.
      Electroacupuncture is advantageous at analgesia and the warming needle
      moxibustion is at relieving joint stiffness. The total efficacy of
      electroacupuncture is superior to that of the warming needle moxibustion.

PMID- 22650123
TI  - [Overactive bladder after transurethral resection of prostate treated with
      electroacupuncture therapy and tolterodine].
AB  - OBJECTIVE: To evaluate the therapeutic effect of overactive bladder after
      transurethral resection of prostate (TURP) preventively treated with
      electroacupuncture and Tolterodine. METHODS: One hundred and twenty cases of
      benign prostate hyperplasia of TURP were randomly divided into an
      electroacupuncture and medicine group, an electroacupuncture group, a medicine
      group and a control group, 30 cases in each group. All the patients were treated
      with TURP under the continuous epidural anesthesia, and the catheter was retained
      for 5-7 days. In electroacupuncture group, before the surgery of the same day,
      Huiyang (BL 35), Ciliao (BL 32), Qugu (CV 2) and Huiyin (CV 1) were acupunctured
      with electroacupuncture for 30 min, once a day, 5-7 days' treatment was applied.
      In medicine group, Tolterodine Tartrate tablet was taken for 2 mg in the morning
      of surgery day, twice a day and treatment was applied for 5-7 days. In
      electroacupuncture and medicine group, the comprehensive therapies above in both
      electroacupuncture group and medicine group were applied. In control group,
      Pethidine of 50 mg was given by intramuscular injection when bladder was
      overactive, combined with Anisodamine injection of 10 mg according to the
      symptoms. The frequency and lasting time of bladder overactivity were compared
      within 72 hours after TURP in each group. RESULTS: After TURP, the frequency of
      bladder overactivity were 2-4 times a day, and lasted for 5-15 min each time in
      control group. The frequency and lasting time of bladder overactivity in
      treatment groups at different time were less than those in control group (P <
      0.01, P < 0.001). There was no significant difference in comparison of frequency
      and lasting time of bladder overactivity between electroacupuncture and medicine
      group (all P > 0.05). The frequency and lasting time of bladder hyperactivity in
      electroacupuncture and medicine group were less than those in the
      electroacupuncture group and the medicine group at 24 hours, 24-48 hours, 48-72
      hours after TUPR (P < 0.05, P < 0.01, P < 0.001). CONCLUSION: After TURP, early
      prevention of combined therapy of electroacupuncture and Tolterodine with oral
      administration is superior to that of electroacupuncture therapy or Tolterodine
      for overactive bladder treatment, and it is the safe and effective method to
      treat overactive bladder.

PMID- 22650124
TI  - [Case of suspected paraneoplastic neurological syndromes].

PMID- 22650125
TI  - [Clinical observation of the impacts and safety of electroacupuncture at
      Sanyinjiao (SP 6) on labor].
AB  - OBJECTIVE: To observe the impacts of electroacupuncture (EA) at Sanyinjiao (SP 6)
      on labor and assess its safety. METHODS: The random and single-blind method was
      adopted to divide 111 cases of the puerperas of natural delivery into an EA group
      (38 cases), a sham-acupuncture group (37 cases) and a blank control group (36
      cases). In EA group, Sanyinjiao (SP 6) was selected and stimulated with Han's
      acupoint nerve stimulator (HANS). In the sham-acupuncture group, the puerperas
      were stimulated only with the needle tube, needle removed in advance and they
      felt subjectively to be needled. Afterward, the filiform needle was attached to
      Sanyinjiao (SP 6) with the needle tip wrapped with the adhesive plaster in
      advance, then HANS which one conducting wire was cut off in was connected. In the
      blank control group, no any treatment was applied, but the same indices were
      recorded at corresponding time points. The blood pressure and the heart rate of
      the puerperas as well as the heart rate of fetus were measured in 20 min of EA
      and 30 min after needle removal in three groups separately. The bleeding 24 h
      after labor and 1 min Apger score of the newborns were observed. RESULTS: In EA
      group, the active phase of the 1st labor stage ((4.38 +/- 1.76)h) was shorter
      than that ((5.28 +/- 2.41)h) in the blank control group and that ((5.38 +/-
      2.36)h) in the sham-acupuncture group, presenting statistically significant
      differences (all P < 0.05). In the latent phase of the 1st labor stage and the
      2nd and 3rd stages, in the comparison of the blood pressure and the heart rate of
      the puerperas as well as the heart rate of fetus after EA, the bleeding 24 h
      after labor and 1 min Apger score of the newborns among three groups, there were
      no statistically significant differences (all P > 0.05). CONCLUSION: EA at
      Sanyinjiao (SP 6) can shorten the duration of the active phase of the 1st labor
      stage. It is safe for either the puerpera or the fetus and can assist the
      parturition quality in clinic.

PMID- 22650126
TI  - [Moderate and severe sudden deafness treated with low-energy laser irradiation
      combined with auricular acupoint sticking].
AB  - OBJECTIVE: To test the therapeutic effect on moderate and severe sudden deafness
      treated with low-energy laser irradiation on acupoint and external auditory canal
      combined with auricular point sticking (APS) and as compared with
      electroacupuncture. METHODS: Two hundred and fifty-eight cases of moderate and
      severe sudden hearing loss were randomly divided into an observation group 1, an
      observation group 2 and a control group, 86 cases in each group. In three groups,
      10% low molecular Dextran 500 mL were used for intravenous infusion. Based on the
      above treatment, the observation group 1 was treated with low-energy laser
      irradiation on acupoint and external auditory canal (such as Ermen (TE 21),
      Tinggong (SI 19) and Tinghui (GB 2)), combined with APS at Gan (liver), Shen
      (kidney) and Neifenmi (endorine), etc. The observation group 2 was treated with
      electroacupuncture at the same acupoints as those point irradiation in
      observation group 1. Fifteen days made one session. The therapeutic effects were
      evaluated after one and two sessions. RESULTS: After two sessions, The cured rate
      was 40.7% (35/86) in observation group 1 and 38.4% (33/86) in observation group
      2,which were superior to 25.6% (22/86) in control group (both P < 0.05). Compared
      with one session, the therapeutic effects after two sessions were better in two
      observation groups (both P < 0.05), but there was no significant difference
      between two groups (both P > 0.05). In comparison of the improvements of
      frequency audiometry and auditory function, the two observation groups were
      better than those in control group (P < 0.05, P < 0.01), and the improvements
      after two sessions were better in two observation groups (both P < 0.01).
      CONCLUSION: Both of low-energy laser irradiation on acupoint and external
      auditory canal combined with APS and electroacupuncture are able to decrease
      frequency audiometry, improve auditory function, and the therapeutic effects are
      better with prolongation of treatment time. The clinical efficacy of above two
      the rapies on moderate and severe sudden deafness is superior remarkably to that
      of conventional treatment. The therapy of low-energy laser irradiation on
      acupoint and external auditory canal combined with APS can replace the
      electroacupuncture therapy in treating moderate and severe sudden deafness.

PMID- 22650127
TI  - [Treatment of herpes zoster with cotton sheet moxibustion: multicentral
      randomized controlled trial].
AB  - OBJECTIVE: To compare the therapeutic effects and safety of herpes zoster treated
      by the cotton sheet moxibustion combined with the plum-blossom-needle tapping
      therapy to western medicine. METHODS: The multicentral random controlled method
      was adopted, 120 cases of herpes zoster were randomly divided into a
      comprehensive treatment group and a western medication group, 60 cases in each
      one. In the comprehensive treatment group, the tapping therapy of plum blossom
      needle was applied to the foci, corresponding Jiaji (EX-B 2), Quchi (LI 11),
      Waiguan (TE 5), Zusanli (ST 36), Taichong (LR 3), etc. Afterward, the cotton
      sheet moxibustion was given. In western medication group, Acyclovir ointment for
      external application, Valaciclovir Hydrochloride tablets and Vitamin B1 for oral
      administration were prescribed. In 7 days of treatment, the clinical symptom
      score, effect time, efficacy and safety were observed before and after treatment
      between two groups. The recurrence of disease was followed up for 1 month.
      RESULTS: In the comprehensive treatment group, the cured rate and the total
      effective rate were 80.0% (48/60) and 98.3% (59/60) separately, which were
      significantly better than 45.0% (27/60) and 71.7% (43/60) in western medication
      group separately (P < 0.01, P < 0.05). After treatment, in either group, the
      scores of clinical symptoms such as pain rating index (PRI), Visual Analogue
      Scale (VAS), present pain intensity (PPI), skin lesion and sleeping score, etc.
      were all reduced significantly (P < 0.01, P < 0.05). The score reducing was much
      more obvious in the comprehensive treatment group (P < 0.01, P < 0.05). In the
      comprehensive treatment group, the time of pain stopping, the time of blister
      stopping, the time of scarring and the time of healing were all shorter tha tn
      those in western medication group (P < 0.01, P < 0.05). In the follow-up
      observation, 1 case (1.6%) was recurred in the comprehensive treatment group and
      8 cases (13.3%) were in western medication group. In western medication group, 6
      cases presented mild adverse reactions. CONCLUSION: The cotton sheet moxibustion
      combined with the plum-blossom-needle tapping therapy is advantageous at good
      efficacy, quick effect and short-time treatment for herpes zoster, which is
      apparently superior to the treatment with Acyclovir ointment for external
      application, Valaciclovir Hydrochloride tablets and Vitamin B1 for oral
      administration. It is the safe and effective therapy.

PMID- 22650128
TI  - [Neuromyelitis optica: a case report].

PMID- 22650129
TI  - [Effect of quantitative acupuncture manipulation on the skin temperature of
      acupoints].
AB  - OBJECTIVE: To verify the effect of lifting-thrusting reinforcing manipulation at
      Hegu (LI 4) of the right side on skin temperature on the Large Intestine
      Meridian. METHODS: Thirty healthy volunteers were needled at Hegu (LI 4) on the
      right side with lifting-thrusting reinforcing manipulation at the depth of 5 - 8
      mm, 100 times/min in freqency for 1 min. With PowerLab 8/30 eight-channel high
      speed recorders and specially equipped skin temperature detector, the
      temperatures of Shangyang (LI 1) on the bilateral side, Hegu (LI 4) and Kouheliao
      (LI 19) on the left side were tested at the time 30 min before the needling, 1
      min during the needling and 30 min after the needling. RESULTS: After the lifting
      thrusting reinforcing manipulation on the right Hegu (LI 4), the average skin
      temperature (27.89 +/- 3.56) degrees C before the needling at the left Hegu (LI
      4) was increased to (28.30 +/- 2.81) degrees C, the temperature of right
      Shangyang (LI 1) (24.57 +/- 4.29) degrees C was increased to (26.30 +/- 4.32)
      degrees C, left Shangyang (LI 1) (25.13 +/- 5.07) degrees C to (26.58 +/- 4.92)
      degrees C and left Kouheliao (LI 19) (32.11 +/- 1.68) degrees C to (32.25 +/-
      2.15) degrees C, all of which were significantly improved to different degrees (P
      < 0.01, P < 0.05). CONCLUSION: The lifting-thrusting reinforcing manipulation has
      an effect of increasing skin temperature of acupoints, and the temperature
      changes after needling are along meridians and have specificity of acupoins.

PMID- 22650130
TI  - [The responses of moxibustion and the countermeasures].
AB  - To make a distinction among the local response of body, the moxibustion
      sensation, its influence on the disease, adverse reaction and others during and
      after the moxibustion treatment, and explore the countermeasures to these
      reactions in order to guide the clinical practice. Of them, the responses of the
      body surface and local acupoints are usual one of the bases to assess the
      moxibustion effect, while the occurs of moxibustion sensation and its influence
      on the disease are normal, which is not necessary to deal with, and the adverse
      reaction and others could be handled according to the different situations.

PMID- 22650131
TI  - [One hundred and thirty-six cases of insomnia of disharmony between the heart and
      kidney treated by acupuncture].

PMID- 22650132
TI  - [Effects of acupuncture on the expression of Cx43 in different acupoints of
      rats].
AB  - OBJECTIVE: To observe the differences of the expression of Cx43 in rats'
      acupoints and sham-acupoint when needled blocks, and explore the relatively
      specificity of acupoints. METHOD: Twenty Wistar rats were randomly divided into
      two groups: an acupuncture group and a control group, ten in each group. The rats
      in the control group were not treated and sacrificed directly to by air embolism;
      the rats in the acupuncture group were needled at "Neiguan (PC 6)", "Zusanli (ST
      36)", "Dazhui (GV 14)" and "Guanyuan (CV 4)", Sham-acupoints were on 1 cm next to
      each of the above acupoints and "Yongquan (KI 1)" were needled by hand
      manipulation, retented needles for 30 min, then all the rats were sacrificed by
      air embolism. With the rats fixed, the tissue blocks at the acupoints and sham
      acupoints were collected, then quick-frozen and cut into sections. The sections
      were stained by immunohistochemical method (Cx43). RESULTS: The expression of the
      rats' Cx43 at the acupoints was significantly higher than that at the non-points
      in both groups (all P < 0.01). The expression of Cx43 at the acupoints in the
      acupuncture group was significantly higher than that in the control group (all P
      < 0.01). CONCLUSION: The expression of Cx43 at acupoints and non-points is
      significantly different, which indicates that the acupoints are actually existed
      and have relatively specificity.

PMID- 22650133
TI  - [Effects of electroacupuncture of "Shuanggu Yitong" prescription on the T
      lymphocyte subset proportions in aging rats].
AB  - OBJECTIVE: To explore the mechanism of electroacupuncture of "Shuanggu Yitong"
      prescription on postponing aging. METHODS: Forty 3-month SD rats, male only, 30
      rats were made sub-acute aging model by D-galactose s.c. injection continuously
      for 42 d, and rest of the rats, 10, were divided into a normal control group.
      After the modeling, the sub-acute aging model rats were randomly into a Shuanggu
      Yitong group [electroacupuncture at "Guanyuan" (CV 4) and "Zusanli" (ST 36), hand
      needle at "Baihui" (GV 20)], an acupuncture control group [electroacupuncture at
      "Weizhong" (BL 40) and "Shuifen" (CV 9), hand needle at "Yintang" (GV 29)] and an
      aging model group, ten in each one. The treatment was given once in a day, six of
      which made a course. The rats in the normal control group and aging model group
      were not received any treatment. After the treatment for three weeks, the rats
      were put to death and their spleen index, thymus index and the T lymphocytes
      subgroups (CD8(+) T/T cell and CD8(+) CD28(-) T/CD8(+) T cell) were tested.
      RESULTS: The spleen index (1.74 +/- 0.059) and thymus index (0.64 +/- 0.039) in
      the aging model group was obviously lower than those in the normal control group
      (1.93 +/- 0.061), (0.81 +/- 0.053) respectively (both P < 0.05); the CD8(+) CD28(
      ) T/CD8(+) T cell percentages (26.28 +/- 4.69)% and CD8(+) T/T cell percentages
      (43.33 +/- 2.84)% in the aging model group were both significantly higher than
      those (15.08 +/- 5.58)% (P < 0.01), (34.70 +/- 4.24)% (P < 0.01) in the normal
      control group. Compared with the aging model group, the spleen index (1.91 +/-
      0.081) and thymus index (0.79 +/- 0.080) in the Shuanggu Yitong group were
      significantly higher (both P < 0.05), but obviously decreased with the percentage
      of CD8(+) CD28(-) T/CD8(+) T cell (18.07 +/- 1.73) (P < 0.01); the percentage of
      CD8(+) CD28(-) T/CD8(+) T cell (18.07 +/- 1.73)% in the acupuncture control group
      was also lower than the aging model group (P < 0.05), but more obvious reduce for
      the Shuanggu Yitong group (P < 0.05). CONCLUSION: The treatment of Shuanggu
      Yitong prescription could regulate the proportions of the T lymphocyte subset,
      and slow down the immunosenescence of subacute aging model rats induced by D
      galactose.

PMID- 22650134
TI  - [Professor DONG Gui-rong's experience for the treatment of peripheral facial
      paralysis].
AB  - Professor DONG Gui-rong's theoretical principle and manipulation points for
      peripheral facial paralysis were introduced in details from the angels of
      syndrome differentiation, timing, acupoint prescription and needling methods. For
      the syndrome differentiation and timing, the professor emphasized to check the
      treatment timing and follow the symptoms, which should be treated by stages,
      besides, it was necessary to find and distinguish the reason and nature of
      diseases to have a combined treatment of tendons and muscles. For the acupoint
      prescription and needling methods, he has proposed that the acupoints selection
      should be compatible of distal and lacal, and made a best of Baihui (GV 20) to
      regulate the whole yang qi, also he has paid much attention to the needling
      methods and staging treatment. Under the consideration of late stage of
      peripheral facial paralysis, based on syndrome differentiation Back-shu points
      have been selected to regulate zang-fu function, should achieve much better
      therapeutic effect.

PMID- 22650135
TI  - [ZHANG Ren's experience of treatment on glaucoma with acupuncture].
AB  - ZHANG Ren, a chief physician, his experience of treatment on glaucoma with
      acupuncture of removing the stagnated live qi and activating blood circulation is
      introduced in this article. The treatment is applicable on primary open-angle
      glaucoma, and especially effective for normal tension glaucoma. His basic point
      prescription is: Muchuang (GB 16), Taiyang (EX-NH 5), Fengchi (GB 20), Xingjian
      (LR 2), Xinming1 (Extra), Shangjingming (Extra), Chengqi (ST 1), Shangtianzhu
      (Extra), etc. Meanwhile, supplementary methods such as acupoint injection, ear
      therapy and dermal needles are also adopted to improve the eye symptoms and
      recover the vision in a certain degree. Details of the manipulations are
      expounded and typical cases are illustrated in the article as well.

PMID- 22650136
TI  - [Discussion about acupuncture anesthesia applied to nasal operation].
AB  - In view of the characteristics of different analgesic methods applied to nasal
      operation, the principle of point selection in acupuncture anesthesia, the
      frequency of electroacupuncture and the assessment of operation, it was stated
      that the compound acupuncture anesthesia not only prevented from incomplete
      analgesia of local anesthesia, but also avoided the adverse reactions of general
      anesthesia in this paper. Moreover, by reducing the dose of narcotics, the unique
      advantage of acupuncture anesthesia could be displayed. At present, it was
      initially believed that a satisfactory analgesia could be achieved by acupuncture
      at Yingxiang (LI 2) and Yintang (EX-HN 3), with 30 Hz, continuous wave. But there
      were not many clinical reports on the application of acupuncture anesthesia in
      nasal endoscopic operation and the operation was not normalized enough. It was
      expected to optimize the operation procedure of nasal operation under acupuncture
      anesthesia and promote the clinical practice of it.

PMID- 22650137
TI  - [Acupuncture at Hegu (LI 4) for 18 cases of pain during CT-guided percutaneous
      radiofrequency ablation in hepatic tumor patients].

PMID- 22650138
TI  - [Compliance guarantee in acupuncture clinical research].
AB  - Through review of the major databases in English and Chinese, it is found that
      there is an absence of articles on special coverage of compliance of research
      fellows and testees in acupuncture clinical trials. Therefore, the author
      proposed (1) The compliance of research fellows should be guaranteed through
      proper work division with reasonable, standard and strict research designation as
      well as comprehensive systems of selection, supervision and estimation. (2) The
      compliance of testees should be guaranteed through enhancing of the right to
      know, improving of the medical environment and constructing a better doctor
      patient relationship. Therefore, the compliance of clinical trials can be
      improved, the quality of clinical research enhanced and the reliability of the
      research results can be guaranteed.

PMID- 22650139
TI  - [Expertise-based randomized controlled trials and its application in acupuncture
      clinical research].
AB  - Through introduction of the methodological mechanism and comparison with classic
      randomized controlled trial, the status and the applicability of the expertise
      based randomized controlled trials in clinic are explored, and its
      characteristics in acupuncture clinical application are analyzed. It is held that
      expertise-based randomized controlled trial is more suitable for the acupuncture
      clinical research, especially for acupuncture practice which emphasizes
      manipulations and different schools.

PMID- 22650140
TI  - [New percutaneous absorption herbal patch for asthma of paracmasis and its effect
      on the relative transcription factors of patients].
AB  - OBJECTIVE: To observe the therapeutic effect and mechanism of new percutaneous
      absorption herbal patch for asthma of paracmasis, and to optimize the form of the
      patch. METHODS: One hundred and twenty cases of paracmasis asthma were randomly
      divided into medicine patch group, medicinal vesiculation group and western
      medication group with 40 cases for each. The new percutaneous absorption herbal
      patch was applied on medicine patch group. Traditional medicinal herbs cake of
      the hospital were applied on medicinal vesiculation group. Feishu (BL 13),
      Fengmen (BL 12) and Dazhui (GV 14) were adopted for both groups. Each patch was
      applied for 6 hours and once every other day. Accuhaler was applied on the
      western medicine group with 2 inhalations a time and twice a day. Clinical
      symptom scores, number of attacks and asymtomatic days were observed right
      before, after and half a year after the treatment. Meanwhile, the expression
      level of IgE, IL-4, GATA-3 mRNA and T-bet mRNA were observed and compared before
      and after the treatment. RESULTS: Clinical symptom scores of all the 3 groups
      were improved (all P < 0.01). The differences of the total effective rate, number
      of attacks and asymtomatic days of all the 3 groups are without statistical
      significance (all P > 0.05). However, the long-term therapeutic effect in half a
      year after the treatment showed that the total effective rate of the medicine
      patch group was 80.0% (32/40), and the medicinal vesiculation group was 70.0%
      (28/40). Both of the them were obviously higher than 47.5% (19/40) of the western
      medicine group (P < 0.01, P < 0.05). And the medicine patch group surpassed the
      other 2 groups in controlling the number of attacks and increasing the
      asymtomatic days (P < 0.05, P < 0.01). The level of IgE and IL-4 of all the 3
      groups decreased sharply after the treatment (P < 0.05, P < 0.01). And there was
      no statistic significance in differences among groups (all P > 0.05). The level
      of GATA-3 mRNA was obviously decreased, while the level of T-bet mRNA was
      obviouly increased in the medicine patch and medicinal vesiculation groups (P <
      0.05, P < 0.01). And the medicine patch group had obvious superiority on
      increasing the level of T-bet mRNA when compared with the medicinal vesiculation
      and western medicine groups (P < 0.01, P < 0.05). CONCLUSION: It is concluded
      that the new percutaneous absorption herbal patch has exact effect on asthma. The
      treatment may reverse the imbalance condition of Th1/Th2 through regulation on
      cell factor and its specific transcription factors.

PMID- 22650141
TI  - [Comparative study of bloodletting therapy between traditional Chinese medicine
      and Tibetan medicine].
AB  - The comparative study of bloodletting therapy between traditional Chinese
      medicine and Tibetan medicine in view of history development, theoretic basis,
      bloodletting location, bloodletting tool, operation method, bloodletting amount,
      indications, contraindications and the others are conducted in this paper. It is
      pointed out that the bloodletting therapy could be better carried forward and
      developed through the interaction and integration of bloodletting therapy between
      traditional Chinese medicine and Tibetan medicine in term of the theoretic,
      practical and development patterns under the guidance of these two different
      medical theoretical systems.

PMID- 22650142
TI  - [The exploration of the academic thought of external treatment master-Wu ShiJi].
AB  - To explore Wu Shiji's academic thought, his external treatment method were
      arranged and summarized, such as treatment based on triple energizer
      differentiation, the theory of plaster heals various disease and the combination
      of the application of acupuncture, moxibustion and plaster etc. It has been
      proved that Wu's external treatment had compiled all the advantages of each
      school of Chinese medicine before his era, rich in content and convenient to use.
      So it values highly in clinical practice and has provided great convenience for
      the modern clinical research of external treatment.

PMID- 22650143
TI  - [Professor YANG Zhao-min's contribution to the education of modern acupuncture
      and moxibustion].
AB  - It was completely collected and summarized the teaching history and the relevant
      historical materials of Professor YANG Zhao-min via consulting the literatures,
      investigation, interview, etc. in this paper. The summaries indicated that from
      the beginning of running a school, Professor YANG Zhao-min adhered to the CHENG's
      moral, worked hard and successfully explored and practiced the training pattern
      of teaching tour for the personnel training of acupuncture and moxibustion. He
      established the specialty of acupuncture and moxibustion, formatted courses and
      inherited the feature of practice teaching. He was in charge of the compilation
      of textbook and engaged in scientific innovation. He inherited the past and
      forged ahead into the future and had made the decision to cultivate the personnel
      of acupuncture and moxibustion. Professor YANG Zhao-min had practiced and
      developed the modern educational thought from the CHENG Dan-an and had made the
      important contribution to the training of acupuncture and moxibustion
      professionals.

PMID- 22650144
TI  - [Electroacupuncture combined with acupoint injection for 40 cases of comatose due
      to craniocerebral trauma].

PMID- 22650145
TI  - [Of clinical reseach on cervical spondylosis treated with acupoint injection in
      recent five years].
AB  - Electronic retrieval was carried out on literatures from the period of May 1,
      2006 and June 1, 2011 in databases of PubMed, ISI web of knowledge and CNKI. The
      selected literatures were summarized and classified from three aspects of
      acupoints selection, medication selection and manipulations. It is concluded that
      cervical Jiaji (EX-B 2) points, Fengchi (GB 20) and Ashi points, etc. are common
      acupoints. The medications contain simple Chinese herbs (Danggui injectio, etc.)
      and compound Chinese herbs (compound Danggui injectio, etc.), simple western
      medicine (vitamin B family, etc.) and Chinese herbs combined with western
      medicine (compound Danggui injectio combined with vitamin B12, etc.). Disposable
      syringes are used for injection equipment. Acupoint injection in treating
      cervical spondylosis is effective. However, mechanism studies is still in
      deficient since most of the researches focus on clinical observation.
      Manipulation of acupoint injection is not standardized. Laws of clinical effect
      are not clear. Thus, the above mentioned defects are still remained for further
      improvement.

PMID- 22650146
TI  - Hydroxyl radical reaction with trans-resveratrol: initial carbon radical adduct
      formation followed by rearrangement to phenoxyl radical.
AB  - In the reaction between trans-resveratrol (resveratrol) and the hydroxyl radical,
      kinetic product control leads to a short-lived hydroxyl radical adduct with an
      absorption maximum at 420 nm and a lifetime of 0.21 +/- 0.01 MUs (anaerobic
      acetonitrile at 25  degrees C) as shown by laser flash photolysis using N
      hydroxypyridine-2(1H)-thione (N-HPT) as a "photo-Fenton" reagent. The transient
      spectra of the radical adduct are in agreement with density functional theory
      (DFT) calculations showing an absorption maximum at 442 or 422 nm for C2 and C6
      hydroxyl adducts, respectively, and showing the lowest energy for the transition
      state leading to the C2 adduct compared to other radical products. From this
      initial product, the relative long-lived 4'-phenoxyl radical of resveratrol (tau
      = 9.9 +/- 0.9 MUs) with an absorption maximum at 390 nm is formed in a process
      with a time constant (tau = 0.21 +/- 0.01 MUs) similar to the decay constant for
      the C2 hydroxyl adduct (or a C2/C6 hydroxyl adduct mixture) and in agreement with
      thermodynamics identifying this product as the most stable resveratrol radical.
      The hydroxyl radical adduct to phenoxyl radical conversion with concomitant water
      dissociation has a rate constant of 5 * 10(6) s(-1) and may occur by
      intramolecular hydrogen atom transfer or by stepwise proton-assisted electron
      transfer. Photolysis of N-HPT also leads to a thiyl radical which adds to
      resveratrol in a parallel reaction forming a sulfur radical adduct with a
      lifetime of 0.28 +/- 0.04 MUs and an absorption maximum at 483 nm.

PMID- 22650147
TI  - Forsterite dissolution in saline water at elevated temperature and high CO2
      pressure.
AB  - The rates and mechanisms of magnesium silicate dissolution can control the
      aqueous chemistry in ways that influence carbonate mineral precipitation during
      geologic carbon sequestration (GCS). A series of batch experiments was performed
      with forsterite (Mg(1.81)Fe(0.19)SiO(4)) powder to determine the effects of
      pressure (10-100 bar CO(2)), temperature (25-100  degrees C), and salinity (0
      50,000 mg/L NaCl) on its dissolution rate at conditions relevant to GCS.
      Dissolution rates and products were determined by analysis of the aqueous phase,
      equilibrium and reaction path modeling, and solid phase characterization by
      scanning electron microscopy and X-ray diffraction. After an initially rapid
      dissolution period, the dissolution rate declined significantly, an effect that
      is attributed to the formation of a silica-rich layer at the forsterite surface.
      The initial dissolution rate increased with increasing temperature and increasing
      CO(2) pressure; the effect of CO(2) was through its influence on the pH. The
      dissolution rate was enhanced by NaCl, which may have been due to its inhibition
      of the formation of a silica-rich surface layer. The experimental results provide
      information about magnesium silicate dissolution at conditions that will be
      encountered during GCS that can be used to predict the fate of CO(2) and the
      evolution of subsurface geochemistry following CO(2) injection.

PMID- 22650148
TI  - Virosaines A and B, two new birdcage-shaped Securinega alkaloids with an
      unprecedented skeleton from Flueggea virosa.
AB  - Two new Securinega alkaloids, virosaines A (1) and B (2), were isolated from the
      twigs and leaves of Flueggea virosa. The structures and absolute configurations
      were elucidated by means of NMR, X-ray diffraction, and CD analyses. Compounds 1
      and 2 represent the first examples of Securinega alkaloids bearing a 7-oxa-1
      azabicyclo[3.2.1]octane ring system, whose plausible biogenetic pathways were
      also proposed.

PMID- 22650149
TI  - Porous metalloporphyrinic frameworks constructed from metal 5,10,15,20
      tetrakis(3,5-biscarboxylphenyl)porphyrin for highly efficient and selective
      catalytic oxidation of alkylbenzenes.
AB  - We incorporate metal 5,10,15,20-tetrakis(3,5-biscarboxylphenyl)porphyrin (M
      H(8)OCPP), for the first time, into porous metal-organic frameworks. The self
      assembled porous metalloporphyrinic frameworks [Mn(5)Cl(2)(MnCl
      OCPP)(DMF)(4)(H(2)O)(4)].2DMF.8CH(3)COOH.14H(2)O (ZJU-18; ZJU = Zhejiang
      University), [Mn(5)Cl(2)(Ni-OCPP)(H(2)O)(8)].7DMF.6CH(3)COOH.11H(2)O (ZJU-19),
      and [Cd(5)Cl(2)(MnCl-OCPP)(H(2)O)(6)].13DMF.2CH(3)COOH.9H(2)O (ZJU-20) are
      isostructural as revealed by their single X-ray crystal structures. The
      metalloporphyrin octacarboxylates (M-OCPP) (M = Mn(III)Cl for ZJU-18 and ZJU-20,
      M = Ni(II) for ZJU-19) are bridged by binuclear and trinuclear metal carboxylate
      secondary building units to form a 3-periodic, binodal, edge-transitive net with
      Reticular Chemistry Structure Resource symbol tbo with pore windows of about 11.5
      A and pore cages about 21.3 A in diameter. The porous nature of these
      metalloporphyrinic frameworks is further established by sorption studies in which
      different substrates such as ethanol, acetonitrile, acetone, cyclohexane,
      benzene, toluene, ethylbenzene, and acetophenone can readily have access to the
      pores. Their catalytic activities for the oxidation of alkylbenzenes were
      examined at 65  degrees C using tert-butyl hydroperoxide as the oxidant. The
      results indicate that ZJU-18 is much superior to ZJU-19, ZJU-20, and homogeneous
      molecular MnCl-Me(8)OCPP, exhibiting highly efficient and selective oxidation of
      ethylbenzene to acetophenone in quantitative >99% yield and a turnover number of
      8076 after 48 h.

PMID- 22650150
TI  - Prevalence and risk factors associated with dry eye syndrome among senior high
      school students in a county of Shandong Province, China.
AB  - PURPOSE: To determine the prevalence and risk factors for dry eye syndrome (DES)
      among senior high school students in Shouguang, a county of Shandong Province,
      China. METHODS: A cross-sectional survey was conducted in July 2010, and 1902
      senior high school students were selected by multi-stage sampling to answer a
      questionnaire assessing the prevalence and risk factors for DES. DES was defined
      as the presence of a previous clinical diagnosis of DES or severe symptoms (both
      dryness and irritation constantly or often). Risk factors associated with DES
      were evaluated with a chi(2) test and logistic regression analyses. RESULTS: The
      prevalence of DES was 23.7%. In univariate analysis, myopia (P < 0.0001), contact
      lens wear (P = 0.020), inadequate refractive correction (P < 0.0001), frequent
      self-administered topical ophthalmic medications (P < 0.0001), and poor sleep
      quality (P = 0.007) were significantly associated with DES. In multivariate
      analysis, inadequate refractive correction (P < 0.0001, odds ratio, OR 1.980; 95%
      confidence interval, CI 1.577-2.488), frequent self-administered topical
      ophthalmic medications (P < 0.0001, OR 1.838; 95% CI 1.399-2.410), and poor sleep
      quality (P = 0.001, OR 1.342; 95% CI 1.054-1.709) were significant risk factors
      for DES. CONCLUSIONS: Senior high school students are a neglected population with
      a high prevalence of DES. Preventive measures directed against risks factors for
      DES among senior high school students may help reduce the prevalence and provide
      a positive impact on students' health.

PMID- 22650151
TI  - Competition between H...pi and H...O interactions in furan heterodimers.
AB  - Here the interactions of furan with HZ (Z = CCH, CCF, CN, Cl, and F) are studied
      using a variety of electron correlation methods (MP2, CCSD(T), DFT-SAPT) and
      correlation-consistent triple- and quadruple-zeta basis sets including complete
      basis set (CBS) extrapolation. For Fu-HF all methods agree that a n-type
      structure with a hydrogen bridge between the oxygen lone-pair of furan and the
      hydrogen atom of HF is the global minimum structure. It is found to be
      significantly more stable than a pi-type structure where the hydrogen atom of HF
      points toward the pi system of furan. For the other four dimers MP2 and DFT-SAPT
      predict the pi-type structure to be somewhat more stable, while CCSD(T) favors
      the n-type structure as the global minimum for Fu-HCl and predicts both
      structures as nearly isoenergetic for Fu-HCCH and Fu-HCCF. From a geometrical
      point of view, the Fu-HCN dimer structures are more related to those of the Fu
      HCl complex than to Fu-HCCH. The different behavior of HCCF and HF upon
      complexation with furan evidence the effect of the presence of a pi system in the
      aggregation of fluorine derivatives. It is shown that aggregates of furan cannot
      be understood by means of dipole-dipole and electrostatic analysis only. Yet,
      through a combined and detailed analysis of DFT-SAPT energy contributions and
      resonance effects on the molecular charge distributions a consistent explanation
      of the aggregation of furan with both pi electron rich molecules and halogen
      hydrides is provided.

PMID- 22650152
TI  - Effects of molecular structural variants on serum Krebs von den Lungen-6 levels
      in sarcoidosis.
AB  - BACKGROUND: Serum Krebs von den Lungen-6 (KL-6), which is classified as human
      mucin-1 (MUC1), is used as a marker of sarcoidosis and other interstitial lung
      diseases. However, there remain some limitations due to a lack of information on
      the factors contributing to increased levels of serum KL-6. This study was
      designed to investigate the factors contributing to increased levels of serum KL
      6 by molecular analysis. METHODS: Western blot analysis using anti-KL-6 antibody
      was performed simultaneously on the bronchoalveolar lavage fluid (BALF) and serum
      obtained from 128 subjects with sarcoidosis. RESULTS: KL-6/MUC1 in BALF showed
      three bands and five band patterns. These band patterns were associated with the
      MUC1 genotype and the KL-6 levels. KL-6/MUC1 band patterns in serum were
      dependent on molecular size class in BALF. Significantly increased levels of
      serum KL-6, serum/BALF KL-6 ratio and serum soluble interleukin 2 receptor were
      observed in the subjects with influx of high molecular size KL-6/MUC1 from the
      alveoli to blood circulation. The multivariate linear regression analysis
      involving potentially relevant variables such as age, gender, smoking status,
      lung parenchymal involvement based on radiographical stage and molecular size of
      KL-6/MUC1 in serum showed that the molecular size of KL-6/MUC1 in serum was
      significant independent determinant of serum KL-6 levels. CONCLUSIONS: The
      molecular structural variants of KL-6/MUC1 and its leakage behavior affect serum
      levels of KL-6 in sarcoidosis. This information may assist in the interpretation
      of serum KL-6 levels in sarcoidosis.

PMID- 22650154
TI  - Clostridium sordellii surgical site infection after breast mass excision: case
      report.
AB  - BACKGROUND: Clostridium sordellii infection is a rare condition usually
      associated with obstetric operations. There have been few reports of C. sordellii
      in association with other invasive procedures. The mortality rate of this
      infection approaches 70%. METHODS: Case report and review of the pertinent
      English-language literature. RESULTS: We describe the first known C. sordellii
      infection after excision of a breast mass in an adult female. This patient had a
      prolonged hospital course in the surgical intensive care unit and endured
      multiple surgical debridements. CONCLUSION: Our patient showed many clinical
      signs that have been described in past cases of C. sordellii infection. Although
      the patient had substantial acute morbidity secondary to necessary aggressive
      treatment, she did survive ultimately. Our case serves the purpose of
      establishing future treatment for C. sordellii breast surgical site infections
      with the hope that future treatment may be adapted from our experience.

PMID- 22650153
TI  - Spatial correlation between malaria cases and water-bodies in Anopheles sinensis
      dominated areas of Huang-Huai plain, China.
AB  - BACKGROUND: Malaria re-emerged in the Huang-Huai Plain of central China during
      2006-2008, dominated with Anopheles sinensis as a vector. However, there is no
      information on strategies based on multi-factor analysis to effectively control
      the re-emergence of malaria in these areas. Previous experience indicates some
      relationship between the distribution of water bodies and malaria cases, but more
      detailed data are not available and in-depth studies have not been conducted up
      to now. The objective of this study was to identify the relationship between the
      distribution of water bodies and presentation of malaria cases using spatial
      analysis tools in order to provide guidance to help formulate effective
      strategies for use in controlling the sources of malaria infection, based on the
      identification of risk areas and population. METHODS: The geographic information
      of malaria cases and their surrounding water bodies were collected from Suixi,
      Guoyang, Guzhen, Yingshang, Fengyang and Yongqiao County in Anhui province,
      Yongcheng and Tongbai County in Henan province. All malaria cases distributed in
      113 villages in these 8 counties were collected from the China Information System
      for Disease Control and Prevention and confirmed by household investigation. Data
      on GIS and malaria cases were mapped and analyzed with the software of ArcGIS 9.2
      to identify the spatial correlation between malaria cases and water bodies. The
      distance from households with malaria cases to the nearest water bodies was used
      to calculate the OR value by Chi-square test. The risk area was identified
      through the comparison of OR values in different distances. RESULTS: 357 malaria
      cases and their GPS data as well as surrounding water bodies were collected and
      analyzed. 74% of malaria cases were located within the extent of 60 m proximity
      to the water bodies. The risk rate of people living there and presenting with
      malaria was significantly higher than others (OR = 1.6,95%CI (1.042, 2.463),P <
      0.05). CONCLUSIONS: The results revealed that distribution of water bodies is an
      important factor influencing the occurrence and distribution of malaria cases in
      the An.sinensis areas, and implies that the scope and population within 60 m
      around water bodies are at risk and could be a targeted population for case
      management of malaria.

PMID- 22650158
TI  - Simple and robust approach for passivating and functionalizing surfaces for use
      in complex media.
AB  - Pluronic is a popular triblock copolymer used as a surfactant to introduce
      hydrophilic coatings onto many different types of material surfaces, from
      engineering to biomedical applications. Unfortunately, this is limited in its
      ability to resist fouling from complex media (i.e., blood) and leaves the surface
      hard for further modification. Herein, we report a simple, yet robust approach
      for passivating and functionalizing surfaces based on zwitterionic
      poly(carboxybetaine) (PCB) based triblock copolymer, which can be directly
      applied to surfaces to prevent nonspecific protein adsorption from undiluted
      blood plasma, and to provide additional functionalities needed for the attachment
      of biomolecules. Several hydrophobic surfaces including polydimethylsiloxane,
      silanized silica, and self-assembled monolayers are tested to demonstrate its
      applicability to a wide range of systems. This approach provides a robust,
      convenient, and effective surface modification method for real-world applications
      from simple surface passivation to specific targeting in complex media.

PMID- 22650156
TI  - Diagnosing pulmonary aspergillosis in patients with hematological malignancies: a
      multicenter prospective evaluation of an Aspergillus PCR assay and a
      galactomannan ELISA in bronchoalveolar lavage samples.
AB  - OBJECTIVES: Diagnosing invasive pulmonary aspergillosis (IPA) remains a challenge
      in patients with hematological malignancies. The clinical significance of testing
      bronchoalveolar lavage (BAL) samples both with polymerase chain reaction (PCR)
      and Aspergillus galactomannan ELISA (GM) is unclear, and the BAL cutoff for GM
      has not been clearly evaluated yet. METHODS: Using a validated nested PCR assay
      and a GM ELISA, we prospectively examined BAL samples from 87 hematological
      patients at high risk of IPA. Of 76 (87%) evaluable patients, 29 patients had
      proven or probable disease. RESULTS: The receiver operating characteristic (ROC)
      analysis of GM optical density (OD) cutoff levels yielded a BAL OD of 0.5 to be
      optimal. We identified 29 probable or proven cases based on this OD. Sensitivity
      and specificity for BAL GM were 0.79 (95% CI, 0.62-0.9) and 0.96 (95% CI, 0.86
      0.99), respectively. For BAL PCR, sensitivity and specificity were 0.59 (95% CI,
      0.41-0.75) and 0.87 (95% CI, 0.75-0.94), respectively. Combining BAL GM and PCR
      for diagnosis showed a sensitivity and specificity rate of 0.55 (95% CI, 0.38
      0.72) and 1.0 (95% CI, 0.93-1.0), respectively, if positivity was defined by
      positive results for both tests. If either positive BAL GM or positive BAL PCR
      results defined test positivity, the sensitivity was 0.83 (95% CI, 0.65-0.92),
      and the specificity was 0.83 (95% CI, 0.70-0.91) CONCLUSIONS: In terms of optimal
      sensitivity and specificity, a GM OD cutoff of 0.5 was determined for BAL
      samples. Positivity for both GM and Aspergillus PCR in BAL makes a pulmonary
      aspergillosis highly likely.

PMID- 22650155
TI  - Platelet-derived growth factor receptor alpha (PDGFRalpha)-expressing "fibroblast
      like cells" in diabetic and idiopathic gastroparesis of humans.
AB  - BACKGROUND: Emerging evidence suggests that "fibroblast-like cells" (FLC) may
      play a role in the regulation of gastrointestinal (GI) motor function. FLC are
      ultrastructurally distinct from other interstitial cells, including interstitial
      cells of Cajal (ICC), and express small-conductance Ca(2+) -activated K(+)
      channels (SK3). In mice, platelet-derived growth factor receptor alpha
      (PDGFRalpha) antibody has also been shown to label FLC. The aims of this study
      were to determine the morphology and distribution of PDGFRalpha-immunoreactive
      (ir) FLC in human gastric muscle and to determine if FLC are altered in
      gastroparesis, where ICC are reduced. METHODS: Full thickness gastric body
      biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis
      patients were immunolabeled using SK3 and PDGFRalpha staining for FLC and Kit
      staining for ICC. Intramuscular FLC and ICC were quantified. KEY RESULTS:
      Intramuscular PDGFRalpha-ir cells had slender cell bodies and long, thin
      processes and were more abundant in the longitudinal compared with the circular
      muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies
      with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell
      structures showed complete overlap with PDGFRalpha-ir. FLC were in close
      proximity to ICC, but their cell bodies did not overlap. No differences were seen
      in the distribution, morphology, or overall numbers of FLC in gastroparesis
      patients. CONCLUSIONS & INFERENCES: In conclusion, PDGFRalpha identifies FLC in
      human gastric smooth muscle. FLC were not altered in distribution or overall
      numbers in gastroparesis. Additional studies are required to determine their role
      in human GI function.

PMID- 22650157
TI  - Pulseless electrical activity during electroconvulsive therapy: a case report.
AB  - BACKGROUND: Arrhythmias resulting in cardiac arrest during electroconvulsive
      therapy have been reported. Most reported cases of cardiac arrest had asystole as
      the initial rhythm. Pulseless electrical activity as an initial rhythm of cardiac
      arrest during electroconvulsive therapy has never been reported. Also,
      thromboembolism after inflation of pneumatic tourniquet during lower limb surgery
      has been reported but never following tourniquet inflation during an
      electroconvulsive therapy. CASE PRESENTATION: We report a case involving an 81-
      year- old female who presented to us for an electroconvulsive therapy for severe
      depression and developed pulseless electrical activity immediately after
      electroconvulsive therapy. She was successfully resuscitated and was later found
      to have bilateral pulmonary emboli with a complete occlusion of the right lower
      lobe pulmonary artery. The source of embolus was from her left lower extremity
      deep venous thrombus, which we believe, got dislodged intraoperatively after
      inflation of pneumatic tourniquet. Our patient not only survived the massive
      pulmonary embolus, but also showed significant improvement in her mental status
      compared to her pre-admission level at the time of discharge to a sub-acute
      rehabilitation centre. CONCLUSION: We recommend that patients who are elderly and
      at high risk of thromboembolism should selectively undergo a preoperative doppler
      ultrasound for deep venous thrombosis. Also, selective application of tourniquet
      in the upper limb, to monitor for seizure activity, would reduce the incidence of
      pulmonary thrombo-embolism as embolic events are significantly less from deep
      venous thromboses of upper extremities when compared to lower extremities.

PMID- 22650159
TI  - Lipoprotein subclass profiles in individuals with varying degrees of glucose
      tolerance: a population-based study of 9399 Finnish men.
AB  - OBJECTIVES: We investigated serum concentrations of lipoprotein subclass
      particles and their lipid components determined by proton nuclear magnetic
      resonance spectroscopy in a population-based study. DESIGN AND METHODS: A total
      of 9399 Finnish men were included in the study: 3034 men with normal fasting
      glucose and normal glucose tolerance; 4345 with isolated impaired fasting glucose
      (IFG); 312 with isolated impaired glucose tolerance (IGT); 1058 with both IFG and
      IGT; and 650 with newly diagnosed type 2 diabetes (New DM). Lipoprotein
      subclasses included chylomicrons (CM) and largest VLDL particles, other VLDL
      particles (five subclasses), intermediate-density lipoprotein (IDL), LDL (three
      subclasses) and HDL (four subclasses). The phospholipid, triglyceride (TG),
      cholesterol, free cholesterol and cholesterol ester levels of the lipoprotein
      particles were measured. RESULTS: Abnormal glucose tolerance (especially IGT and
      New DM) was significantly associated with increased concentrations of VLDL
      subclass particles and their components (with the exception of very small VLDL
      particles). After further adjustment for total TGs and HDL cholesterol, increased
      lipid concentrations in the CM/largest VLDL particles and in most of the other
      VLDL particles remained significant in individuals with isolated IGT, IFG+IGT and
      New DM. There was a consistent trend towards a decrease in large and an increase
      in small HDL particle concentrations in individuals with hyperglycaemia even
      after adjustment for serum total TGs and HDL cholesterol. CONCLUSIONS: Abnormal
      glucose tolerance modifies the concentrations of lipoprotein subclass particles
      and their lipid components in the circulation and is also related to
      compositional changes in these particles.

PMID- 22650161
TI  - Ectopic intrapulmonary thyroid tissue mimicking metastatic tissue.
AB  - BACKGROUND: Ectopic intrapulmonary thyroid is extremely rare, with only about two
      cases reported in the literature. These cases were found either during the work
      up of a solitary pulmonary nodule or at autopsy. Here, we report a case of
      ectopic intrapulmonary thyroid mimicking multiple pulmonary metastases from an
      endometrioid adenocarcinoma of the uterus. PATIENT FINDINGS: A 50-year-old woman
      presented with dysmenorrhea and menorrhagia. Endometrial curettage of the uterus
      revealed an endometrioid adenocarcinoma. During the staging, multiple pulmonary
      nodules were found. To exclude the possibility of lung metastases of the
      endometrioid adenocarcinoma from the uterus, video-assisted thoracic surgery
      (VATS) with wedge resection was performed for the largest nodule. The
      histopathology for that nodule was entirely consistent with normal thyroid
      tissue. The patient underwent surgery for uterine cancer and was discharged
      without further adjuvant chemotherapy. The remaining intrapulmonary nodules were
      unchanged in size on a serial computed tomography scan. SUMMARY: In this patient,
      pulmonary metastases were initially considered the most likely cause of the
      multiple pulmonary nodules, but the diagnosis of the ectopic intrapulmonary
      thyroid was ultimately made based on VATS-wedge resection for the largest
      pulmonary nodule. The patient was able to avoid any unnecessary systemic
      chemotherapy. CONCLUSIONS: Ectopic intrapulmonary thyroid is extremely rare but
      can be confused with pulmonary metastases from other sites. We are unaware of
      similar cases in the literature.

PMID- 22650160
TI  - Identification of novel subgroup A variants with enhanced receptor binding and
      replicative capacity in primary isolates of anaemogenic strains of feline
      leukaemia virus.
AB  - BACKGROUND: The development of anaemia in feline leukaemia virus (FeLV)-infected
      cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C
      arises from the subgroup that is transmitted, FeLV-A, through alterations in the
      amino acid sequence of the receptor binding domain (RBD) of the envelope
      glycoprotein that result in a shift in the receptor usage and the cell tropism of
      the virus. The factors that influence the transition from subgroup A to subgroup
      C remain unclear, one possibility is that a selective pressure in the host drives
      the acquisition of mutations in the RBD, creating A/C intermediates with enhanced
      abilities to interact with the FeLV-C receptor, FLVCR. In order to understand
      further the emergence of FeLV-C in the infected cat, we examined primary isolates
      of FeLV-C for evidence of FeLV-A variants that bore mutations consistent with a
      gradual evolution from FeLV-A to FeLV-C. RESULTS: Within each isolate of FeLV-C,
      we identified variants that were ostensibly subgroup A by nucleic acid sequence
      comparisons, but which bore mutations in the RBD. One such mutation, N91D, was
      present in multiple isolates and when engineered into a molecular clone of the
      prototypic FeLV-A (Glasgow-1), enhanced replication was noted in feline cells.
      Expression of the N91D Env on murine leukaemia virus (MLV) pseudotypes enhanced
      viral entry mediated by the FeLV-A receptor THTR1 while soluble FeLV-A Env
      bearing the N91D mutation bound more efficiently to mouse or guinea pig cells
      bearing the FeLV-A and -C receptors. Long-term in vitro culture of variants
      bearing the N91D substitution in the presence of anti-FeLV gp70 antibodies did
      not result in the emergence of FeLV-C variants, suggesting that additional
      selective pressures in the infected cat may drive the subsequent evolution from
      subgroup A to subgroup C. CONCLUSIONS: Our data support a model in which variants
      of FeLV-A, bearing subtle differences in the RBD of Env, may be predisposed
      towards enhanced replication in vivo and subsequent conversion to FeLV-C. The
      selection pressures in vivo that drive the emergence of FeLV-C in a proportion of
      infected cats remain to be established.

PMID- 22650162
TI  - Ironing out neurodegeneration: is iron intake important during the teenage years?

PMID- 22650163
TI  - Should the Social Cognition and Emotional Assessment replace standard
      neuropsychological tests for frontotemporal dementia?

PMID- 22650164
TI  - The use of informant-based questionnaires in differentiating mild cognitive
      impairment from normal aging.

PMID- 22650166
TI  - Lacosamide for the treatment of partial-onset seizures.
AB  - Lacosamide (LCM) is an antiepileptic drug approved as adjunctive therapy for
      partial-onset seizures in adults. It has a mechanism of action that differs from
      other antiepileptic drugs in that it selectively enhances sodium channel slow
      inactivation, which is in contrast to 'traditional' sodium channel blockers
      (e.g., carbamazepine, oxcarbazepine, lamotrigine and phenytoin) that primarily
      affect fast inactivation. The pharmacokinetic profile of LCM is well
      characterized and includes a fast rate of absorption, little or no interaction
      with cytochrome P450 isoenzymes, limited effect of age and gender on plasma
      levels, and low potential for drug-drug interactions. Safety and efficacy data
      from three double-blind, placebo-controlled trials, as well as pooled and post
      hoc analyses of these three trials, have been published, and demonstrate the
      safety and rapid-onset efficacy of LCM in adults with treatment-refractory
      partial-onset seizures. LCM is available in tablets and an intravenous
      formulation when oral administration is temporarily not feasible.

PMID- 22650167
TI  - Associations of alcohol consumption with clinical and MRI measures in multiple
      sclerosis.
AB  - While the harmful effects of alcohol abuse are well documented, experimental and
      clinical data support a potential benefit of light to moderate alcohol
      consumption. Cross-sectional studies have suggested an association between
      alcohol consumption and multiple sclerosis (MS) disability. In the absence of
      prospective, longitudinal studies, the causal nature of this relationship cannot
      be established. It remains possible that patients with increased disability
      progression reduce their alcohol intake. Even though there is substantial
      evidence for anti-inflammatory effects of low-to-moderate doses of alcohol, the
      associations need to be interpreted very cautiously. This study discusses the
      current state of knowledge about MS and alcohol consumption, and the limitations
      in conducting research with retrospective data in patients with MS.

PMID- 22650168
TI  - The management of Parkinson's disease in sub-Saharan Africa.
AB  - The vast majority of patients with Parkinson's disease (PD) in sub-Saharan Africa
      are undiagnosed and untreated with impaired quality of life and markedly
      increased mortality rates. PD is a progressive neurodegenerative disorder that
      becomes increasingly common as people age. Diagnosis remains predominantly
      clinical based on motor symptoms: tremor, rigidity, bradykinesia and postural
      instability. In developed countries, it is well recognized and very few patients
      will not be diagnosed and treated. However, in developing countries, such as
      those in sub-Saharan Africa, evidence suggests that most patients are
      undiagnosed, and even if they are diagnosed, they do not have access to
      sustainable, affordable, drug treatment and medical supervision. There is a lack
      of awareness, both within the general population and also among healthcare
      professionals, and many patients seek help from traditional healers. Even if they
      are diagnosed, treatment is often too expensive, and supplies are sporadic. There
      is a great need to increase awareness of PD within the general population and the
      fact that the symptoms are treatable. Education of healthcare workers about PD is
      also important, but a major challenge is there are few doctors and even fewer
      neurologists. Awareness raising and training will be to no avail, unless the
      problem of an affordable, reliable supply of drug treatment can be tackled.

PMID- 22650169
TI  - Recent and future antiepileptic drugs and their impact on cognition: what can we
      expect?
AB  - Cognitive problems are frequently observed in patients with epilepsy and the
      relative contribution of antiepileptic drugs (AEDs) in this respect is
      determinant. During the past few years, a number of new AEDs have been
      introduced, and new compounds will be probably available in the forthcoming
      years. The ideal AED would be the one characterized by good efficacy with no
      negative effects on cognitive functions, mood and behavior. This paper is aimed
      at discussing the potential impact on cognition of a number of new compounds,
      namely lacosamide, rufinamide, retigabine, eslicarbazepine acetate, brivaracetam,
      perampanel and ganaxolone. In almost all cases, specific data on cognitive
      functions are not yet available, and it is possible only to speculate on their
      potential impact considering the mechanism of action and the adverse event
      profile in placebo-controlled studies. Lacosamide, eslicarbazepine acetate and
      probably brivaracetam are promising and will probably exhibit very limited impact
      on cognition. Conversely, retigabine may be more problematic, needing low
      starting doses and slow titration rates to improve cognitive tolerability. Data
      on rufinamide are restricted to special populations such as Lennox-Gastaut
      syndrome. Perampanel and ganaxolone are still in Phase III development, but the
      mechanism of action of these compounds is in line with a more sedative than
      neutral profile.

PMID- 22650170
TI  - Evaluation of the Braak hypothesis: how far can it explain the pathogenesis of
      Parkinson's disease?
AB  - Braak's proposal that, in patients with Parkinson's disease, Lewy bodies and
      neurites progressively invade the brain through regions connected to autonomic
      and olfactory centers remains contentious. Confounding factors include the lack
      of an in vivo marker to examine the progression of Lewy pathology, the
      retrospective nature or absence of clinical information for many cross-sectional
      pathological datasets, and for those with limited disease (clinically or
      neuropathologically), the absence of information concerning additional
      conditions. Despite these data limitations at this time, the brain pathology for
      most patients with typical Parkinson's disease can be predicted using Braak's
      scheme. What this tells us about the pathogenesis of Parkinson's disease will be
      explored in this review.

PMID- 22650171
TI  - Distinguishing essential tremor from Parkinson's disease: bedside tests and
      laboratory evaluations.
AB  - Distinguishing essential tremor from Parkinson's disease can be challenging, both
      in the early stages of these diseases and as these diseases progress. Various
      tremor types (rest, postural, kinetic and intention) may be seen in both
      essential tremor and Parkinson's disease. Furthermore, with time, the two
      diseases may coexist within a single patient. Detailed clinical examination with
      attention to specific features of tremor (frequency, amplitude, pattern and
      distribution) and associated neurological findings may help distinguish patients
      with the two diseases. Laboratory testing may provide information that further
      aids in differentiating the two diseases. These tests include accelerometry and
      surface electromyography, spiral analysis, dopamine transporter imaging,
      olfactory testing and, eventually, postmortem histopathology. These tests have
      limitations and their diagnostic utility requires additional study.

PMID- 22650172
TI  - Autonomic dysfunction in Parkinson's disease.
AB  - Growing recognition of the non-motor features of Parkinson's disease (PD) has led
      to increased awareness of autonomic dysfunction as part of the disease process,
      not only in advanced disease but also early in its course, sometimes even
      preceding the development of the classic motor features of PD. Virtually all
      aspects of autonomic function can become impaired in PD, including
      cardiovascular, gastrointestinal, urological, sexual and thermoregulatory
      function. Recognition of the various autonomic abnormalities of PD is important
      because effective treatment may be available and may measurably improve quality
      of life for individuals with PD.

PMID- 22650173
TI  - Second-generation antiepileptic drugs and pregnancy: a guide for clinicians.
AB  - When treating pregnant women with antiepileptic drugs (AEDs), clinicians have to
      balance potential fetal adverse effects against the risks of uncontrolled
      maternal disease. Only recently have emerging scientic data provided a rational
      basis for treatment decisions considering both aspects. The focus of research is
      currently moving from the first to the second AED generation. Lamotrigine is
      relatively well studied, and data on other novel AEDs, such as levetiracetam,
      oxcarbazepine, topiramate, zonisamide, gabapentin and pregabalin, are in
      progress. Safety issues appear to be favorable for lamotrigine, and preliminary
      results are also promising for levetiracetam and oxcarbazepine. Drugs metabolized
      by uridine-diphospate glucuronosyl transferase or excreted unchanged by the
      kidneys are particularly susceptible to increased body clearance during
      pregnancy. Lamotrigine is subject to both mechanisms, and therapeutic serum
      levels may sometimes be difficult to maintain. The authors review the
      recommendations and clinical research on modern AED treatment during pregnancy,
      highlighting current experience with second-generation drugs.

PMID- 22650174
TI  - The impact of positron emission tomography imaging on the clinical management of
      patients with epilepsy.
AB  - Clinical positron emission tomography (PET) imaging of human epilepsy has a 30
      year history, but it is still searching for its exact role among rapidly
      advancing neuroimaging techniques. The vast majority of epilepsy PET studies used
      this technique to improve detection of epileptic foci for surgical resection.
      Here, we review the main trends emerging from three decades of PET research in
      epilepsy, with a particular emphasis on how PET imaging has impacted on the
      clinical management of patients with intractable epilepsy. While reviewing the
      latest studies, we also present an argument for a changing role of PET and
      molecular imaging in the future, with an increasing focus on epileptogenesis and
      newly discovered molecular mechanisms of epilepsy. These new applications will be
      facilitated by technological advances, such as the use of integrated PET/MRI
      systems and utilization of novel radiotracers, which may also enhance phenotype
      genotype correlations and assist rational, individualized treatment strategies.

PMID- 22650175
TI  - Angiogenic inhibition in high-grade gliomas: past, present and future.
AB  - High-grade gliomas, especially glioblastoma (GBM), are among the most aggressive
      and vascularized tumors. Angiogenesis plays a significant role in tumor growth
      and survival, and thus offers a target for anticancer treatment. Bevacizumab, a
      humanized monoclonal antibody against VEGF, was approved by the US FDA as a
      single agent for the treatment of recurrent glioblastoma. Significant
      radiographic response and progression-free survival were seen with bevacizumab
      treatment. However, benefits to overall survival remain undetermined. Other
      antiangiogenic strategies targeting VEGF, VEGF receptor (VEGFR) and other
      angiogenic factors have also been examined. Tumor progression after
      antiangiogenic treatment is inevitable, and effective salvage therapy is yet to
      be identified. Mechanisms of resistance to antiangiogenic therapy include
      activation of alternative proangiogenic pathways and increased tumor invasion.
      Strategies targeting these escape mechanisms are currently being investigated.
      The use of antiangiogenic drugs is generally well tolerated, although rare and
      potentially life-threatening adverse effects have been identified. With the
      striking antipermeability effect of anti-VEGF inhibitors, assessment of true
      tumor response has become a challenge. The Response Assessment in Neuro-Oncology
      Working Group has developed new criteria for clinical trials in patients with
      high-grade glioma. Identification of neuroimaging advances and biologic markers
      will greatly enhance treatment strategies for these patients.

PMID- 22650177
TI  - Design and synthesis of a novel series of bicyclic heterocycles as potent gamma
      secretase modulators.
AB  - The design and the synthesis of several chemical subclasses of imidazole
      containing gamma-secretase modulators (GSMs) is described. Conformational
      restriction of pyridone 4 into bicyclic pyridone isosteres has led to compounds
      with high in vitro and in vivo potency. This has resulted in the identification
      of benzimidazole 44a as a GSM with low nanomolar potency in vitro. In mouse, rat,
      and dog, this compound displayed the typical gamma-secretase modulatory profile
      by lowering Abeta42 and Abeta40 levels combined with an especially pronounced
      increase in Abeta38 and Abeta37 levels while leaving the total levels of amyloid
      peptides unchanged.

PMID- 22650178
TI  - Proportion of patients with implanted permanent pacemakers with atrial
      fibrillation receiving appropriate medical prophylaxis in North Wales.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with an increased long-term
      risk of stroke, heart failure, and mortality. Previous studies have demonstrated
      the suboptimal use of anticoagulation therapy in patients with AF. METHODS: A
      retrospective survey of patients (N = 1,113) fitted with dual-chamber pacemakers
      found 71 patients (age 69 +/- 35, mean +/- standard deviation) with atrial
      tachycardia and AF (defined as >5 minutes per day). Their medical records and
      anticoagulation status were investigated and used to stratify each patient for
      stroke risk with the Birmingham 2009 schema (CHA(2)DS(2)-VASc) and assessed to
      determine the rate of appropriate thromboembolism (TE) prophylaxis prescription.
      RESULTS: The most common overall concomitant risk factor for stroke was
      hypertension (54%), followed by age >=75 (51%), being female and previous
      stroke/transient ischemic attack/TE (39%). The average CHA(2)DS(2)-VASc score was
      3.7 +/- 1.6. Fifty-six percent of the patients were not receiving appropriate
      anticoagulation therapy. CONCLUSION: This study demonstrates an underutilization
      of the oral anticoagulant warfarin in patients with known AF and that the
      clinicians may not be regarding current stroke risk factors when adopting a
      thromboprophylaxis strategy.

PMID- 22650179
TI  - Is there value in kinetic modeling of thrombin generation? No (unless...).

PMID- 22650181
TI  - New therapeutic strategies for cancer and neurodegeneration emerging from yeast
      cell-based systems.
AB  - Despite great advances in understanding the molecular etiology of cancer and
      neurodegeneration, therapeutic strategies against these diseases are still
      largely lacking. Hence, acceleration of the discovery of new therapeutic agents
      against these pathologies is of enormous interest. This review is focused on the
      role of multi-faceted and expanding yeast cell-based systems in the search for
      new drugs and therapeutic targets in cancer and neurodegeneration. Though the
      obvious limitations of using a microorganism to address human diseases, when used
      in the early phase and with complementary mammalian systems, it can have a
      tremendous impact in the discovery of new therapeutic opportunities. In this
      review, many evidence are provided demonstrating the valuable contribution of
      yeast in this area. Additionally, several yeast target-based drug screening
      approaches based on a readily screenable phenotype on genomic technologies
      increasingly oriented towards genetic and chemical high-throughput analysis are
      addressed. Altogether, with this review, we intend not only to recognize previous
      successes and ongoing work in this area, but also to point out new opportunities
      that may be of interest for yeast as a model organism and as a powerful system in
      the discovery of new lead compounds that have the potential to become novel drugs
      in cancer and neurodegeneration.

PMID- 22650180
TI  - Treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia with
      imatinib combined with a paediatric-based protocol.
AB  - Although the combination of tyrosine kinase inhibitors with chemotherapy is
      widely used for young adults with Philadelphia chromosome positive-acute
      lymphoblastic leukaemia (Ph+ ALL), the outcome and safety of this combination
      using intensive paediatric-based protocols has not been well described. The
      clinical course of 32 adults age 18-60 years with Ph+ ALL treated with a
      paediatric-based protocol plus imatinib was evaluated. The complete response rate
      was 94%. Grade 3-4 infections, neuropathy, myopathy and liver function
      abnormalities were common, resulting in major treatment delays and dose
      reductions, and declines in performance status (physical deconditioning),
      particularly in patients aged 41-60 years. Median and 3-year overall survival
      (OS) was 40.7 months and 53%, respectively, and median and 3-year even-free
      survival (EFS) was 30.1 months and 50%, respectively. OS and EFS were inferior in
      deconditioned patients. Of 16 patients who underwent haematopoietic stem cell
      transplantation (HSCT) in first complete remission, six died of non-relapse
      complications. There was no significant difference in OS and EFS between
      transplanted and non-transplanted patients, based on an intention-to-treat and
      time-to-donor identification analysis. The combination of imatinib with a
      paediatric-based regimen in adults produced high response rates, but was
      associated with considerable toxicity and high non-relapse mortality post-HSCT.

PMID- 22650182
TI  - Attentional asymmetries in a visual orienting task are related to temperament.
AB  - Spatial asymmetries are an intriguing feature of directed attention. Recent
      observations indicate an influence of temperament upon the direction of these
      asymmetries. It is unknown whether this influence generalises to visual orienting
      behaviour. The aim of the current study was therefore to explore the relationship
      between temperament and measures of spatial orienting as a function of target
      hemifield. An exogenous cueing task was administered to 92 healthy participants.
      Temperament was assessed using Carver and White's (1994) Behavioural Inhibition
      System and Behavioural Activation System (BIS/BAS) scales. Individuals with high
      sensitivity to punishment and low sensitivity to reward showed a leftward
      asymmetry of directed attention when there was no informative spatial cue
      provided. This asymmetry was not present when targets were preceded by spatial
      cues that were either valid or invalid. The findings support the notion that
      individual variations in temperament influence spatial asymmetries in visual
      orienting, but only when lateral targets are preceded by a non-directional
      (neutral) cue. The results are discussed in terms of hemispheric asymmetries and
      dopamine activity.

PMID- 22650219
TI  - Ways to reduce cardiovascular disease in diabetes.

PMID- 22650222
TI  - The glycocalyx and cardiovascular disease in diabetes: should we judge the
      endothelium by its cover?
AB  - Patients with diabetes mellitus are characterized by an extraordinary vascular
      vulnerability. Traditionally, glucose-induced damage to the vascular endothelium
      is believed to be one of the first steps in the development of vascular damage.
      However, in the healthy vessel the endothelium is protected by a matrix layer of
      highly glycosylated proteins that form a physical barrier between the endothelium
      and the blood flowing past. Although its presence has been known for half a
      century, this so-called glycocalyx earned little attention from researchers in
      the past because of an underestimation of its size. In the last decade it has
      become clear that its full thickness actually exceeds that of the vascular
      endothelium. Accumulating research into the functional relevance of the
      endothelial glycocalyx suggests an important role for this layer in the
      development of cardiovascular disease in diabetes mellitus. Here we will present
      an overview of the biochemistry of the intact glycocalyx, current methods to
      assess the glycocalyx, and its possible role in the pathophysiology of
      cardiovascular disease in diabetes.

PMID- 22650220
TI  - Cardiovascular disease in children and adolescents with diabetes: where are we,
      and where are we going?
AB  - The increasing prevalence of type 1 and type 2 diabetes mellitus combined with
      advancement in early detection of cardiovascular disease (CVD) has placed CVD as
      a significant concern for preventative pediatric medicine. The public health
      burden of type 2 diabetes is predicted to parallel increasing obesity in children
      with a projected increase of early CVD in adulthood. In this article, we review
      practice guidelines for cardiovascular health in children and adolescents with
      diabetes and data on which they are based. We then focus on imaging modalities
      that are promising tools to expand our understanding of the cardiovascular risk
      imposed on youths with diabetes.

PMID- 22650223
TI  - Cardiovascular disease and oral agent glucose-lowering therapies in the
      management of type 2 diabetes.
AB  - Although glucose-lowering oral agents have been available for clinical use for
      over 60 years, the formal evidence base supporting their advantage and safety in
      regard of cardiovascular (CV) outcomes remains less than optimal. However, a
      synthesis of the evidence results in a high probability of benefit. For
      metformin, the United Kingdom Prospective Diabetes Study (UKPDS) substudy is
      convincing for a definite effect in reducing myocardial infarction (MI), but the
      quantitative extent of that is uncertain. For sulfonylureas, support for
      reduction in MI comes from the UKPDS extension study, where the central estimate
      for risk reduction remains the same as in the original planned end to the study,
      but the greater number of events was statistically significant for the
      sulfonylurea/insulin arm. Other studies do not support the view that metformin
      and sulfonylureas differ with respect to MI or indeed CV outcomes more generally.
      The data available for acarbose, an alpha-glucosidase inhibitor, are weak but not
      of concern, although some positive substudy data are available for people with
      impaired glucose tolerance. For peroxisome proliferator-activated receptor-gamma
      agonists the CV data are more controversial, but the purpose-designed randomized
      controlled trials are clear that pioglitazone is advantageous to placebo (except
      for heart failure [HF]), whereas rosiglitazone is indistinguishable from
      metformin/sulfonylureas (even when including HF data). Lower-quality data do,
      however, lead to significant concerns for MI with rosiglitazone. Early and
      somewhat low-quality data for the dipeptidyl peptidase inhibitors show they are
      safe and hold promise for cardiovascular advantage, with major randomized
      controlled trials being underway. Preliminary CV data are available for one
      sodium/glucose cotransporter 2 inhibitor and look reassuring.

PMID- 22650221
TI  - How to best manage glycemia and non-glycemia during the time of acute myocardial
      infarction.
AB  - Acute myocardial infarction (AMI) is common in patients with diabetes. Reasons
      for this are multifactorial, but all relate to a variety of maladaptive responses
      to acute hyperglycemia. Persistent hyperglycemia is associated with worse left
      ventricular function and higher mortality during AMI, but intervention data are
      far from clear. Although there is a theoretical basis for the use of glucose
      insulin-potassium infusion during AMI, lack of outcome efficacy (and inability to
      reach glycemic targets) in recent randomized trials has resulted in little
      enthusiasm for this strategy. Based on the increasing understanding of the
      dangers of hypoglycemia, while at the same time appreciating the role of
      hyperglycemia in AMI patients, goal glucose levels of 140-180 mg/dL using an
      intravenous insulin infusion while not eating seem reasonable for most patients
      and hospital systems. Non-glycemic therapy for patients with diabetes and AMI has
      benefited from more conclusive data, as this population has greater morbidity and
      mortality than those without diabetes. For ST-elevation myocardial infarction
      (STEMI), reperfusion therapy with primary percutaneous coronary intervention or
      fibrinolysis, antithrombotic therapy to prevent acute stent thrombosis following
      percutaneous coronary intervention or rethrombosis following thrombolysis, and
      initiation of beta-blocker therapy are the current standard of care. Emergency
      coronary artery bypass graft surgery is reserved for the most critically ill. For
      those with non-STEMI, initial reperfusion therapy or fibrinolysis is not
      routinely indicated. Overall, there have been dramatic advances for the treatment
      of people with AMI and diabetes. The use of continuous glucose monitoring in this
      population may allow better ability to safely reach glycemic targets, which it is
      hoped will improve glycemic control.

PMID- 22650224
TI  - Non-insulin injectable treatments (glucagon-like peptide-1 and its analogs) and
      cardiovascular disease.
AB  - Glucagon-like peptide-1 (GLP-1) [GLP-1 (7-36)-amide] plays a fundamental role in
      regulating postprandial nutrient metabolism. GLP-1 acts through a G-protein
      coupled receptor present on the membranes of many tissues, including myocardium
      and endothelium. GLP-1 is cleaved by the dipeptidyl peptidase-4 enzyme to its
      metabolite GLP-1 (9-36)-amide within 1-2 min of its release into the circulation.
      Investigations have been done in humans and in animal models to determine whether
      GLP-1 has effects on the myocardium. Infusions of GLP-1 increase cardiac function
      in ischemic and non-ischemic cardiovascular disease. In humans and animal models,
      constant infusions of GLP-1 decrease the size of infarction and improve
      myocardial function in ischemic/reperfusion injury. In cardiomyopathy and heart
      failure, infusions of GLP-1 improve myocardial function. These beneficial effects
      of GLP-1 on cardiac function are mediated by both GLP-1 receptor activation and
      GLP-1 receptor independent actions. Infusions of the metabolite GLP-1 (9-36)
      amide improve cardiac function in experimental animals with cardiovascular
      disease even though the metabolite does not bind to the GLP-1 receptor. The
      beneficial effects of GLP-1 on the heart occur in the presence of a GLP-1
      receptor antagonist and in animals devoid of GLP-1 receptors. Preliminary data in
      animals with available GLP-1 receptor agonists and cardiac disease suggest that
      exenatide has beneficial effects in porcine models of ischemic heart disease. The
      animal data with liraglutide are inconclusive. Clinical trials with exenatide and
      liraglutide show significant improvements in weight, systolic blood pressure,
      lipid profiles, and other cardiovascular risk factors. Whether these will
      decrease cardiovascular events is currently under investigation.

PMID- 22650225
TI  - Hypoglycemia, diabetes, and cardiovascular disease.
AB  - Cardiovascular disease (CVD) remains the leading cause of death in people with
      diabetes, and the risk of CVD for adults with diabetes is at least two to four
      times the risk in adults without diabetes. Complications of diabetes, including
      not only CVD but also microvascular diseases such as retinopathy and nephropathy,
      are a major health and financial burden. Diabetes is a disease of glucose
      intolerance, and so much of the research on complications has focused on the role
      of hyperglycemia. Clinical trials have clearly demonstrated the role of
      hyperglycemia in microvascular complications of diabetes, but there appears to be
      less evidence for as strong of a relationship between hyperglycemia and CVD in
      people with diabetes. Hypoglycemia has become a more pressing health concern as
      intensive glycemic control has become the standard of care in diabetes. Clinical
      trials of intensive glucose lowering in both type 1 and type 2 diabetes
      populations has resulted in significantly increased hypoglycemia, with no
      decrease in CVD during the trial period, although several studies have shown a
      reduction in CVD with extended follow-up. There is evidence that hypoglycemia may
      adversely affect cardiovascular risk in patients with diabetes, and this is one
      potential explanation for the lack of CVD prevention in trials of intensive
      glycemic control. Hypoglycemia causes a cascade of physiologic effects and may
      induce oxidative stress and cardiac arrhythmias, contribute to sudden cardiac
      death, and cause ischemic cerebral damage, presenting several potential
      mechanisms through which acute and chronic episodes of hypoglycemia may increase
      CVD risk. In this review, we examine the risk factors and prevalence of
      hypoglycemia in diabetes, review the evidence for an association of both acute
      and chronic hypoglycemia with CVD in adults with diabetes, and discuss potential
      mechanisms through which hypoglycemia may adversely affect cardiovascular risk.

PMID- 22650226
TI  - Emerging economies and diabetes and cardiovascular disease.
AB  - Diabetes and cardiovascular diseases (CVDs) are increasing in epidemic
      proportions globally, with the most marked increase in emerging economies. Among
      emerging economies, China and India have the highest numbers of people with
      diabetes and CVD. Over the last two decades, 80% of CVD and diabetes mortality
      occurred in low- and middle-income countries, suggesting that these disorders
      have become a leading threat to public health in most of the developing
      countries. The burden of CVD and diabetes in the developing countries affects the
      productive younger age group, and this has serious economic implications.
      Diabetes shares many characteristics and risk factors with CVD, and thus the risk
      for CVD also escalates with the increase in prevalence of diabetes. Both genetic
      and environmental factors play a major role in causation of diabetes and CVD.
      However, the major drivers of this dual epidemic are demographic changes with
      increased life expectancy, lifestyle changes due to rapid urbanization, and
      industrialization. To reduce the burden of diabetes and CVD in the coming
      decades, emerging economies need to set national goals for early diagnosis,
      effective management, and primary prevention of these disorders. In order to curb
      the epidemic of diabetes and CVD, population-based, multisectoral,
      multidisciplinary, and culturally relevant approaches including various
      departments of the government as well as non-governmental agencies are required.

PMID- 22650227
TI  - Metabolic memory for vascular disease in diabetes.
AB  - Although the terms "metabolic memory" and "legacy effect" have been used to
      describe the prolonged benefits of good blood glucose control, the former is now
      recognized as a phenomenon related to the prolonged harm produced mainly by
      hyperglycemia. At least three randomized clinical trials (Diabetes Control and
      Complications Trial in type 1 diabetes, United Kingdom Prospective Diabetes Study
      and Steno-2 in type 2 diabetes) have demonstrated that patients treated
      intensively for a period of time have a lower risk of micro- and macrovascular
      complications that persists during subsequent follow-up, even after their tight
      control has relented and the levels of glycated hemoglobin in the conventionally
      treated group improve. The mechanisms are not fully understood but most probably
      relate to the physiopathology of vascular complications of diabetes, and in
      recent years a unifying theory has been emerging to understand them. The excess
      superoxide anion produced by the mitochondria in response to hyperglycemia leads
      through disturbances at the nuclear level to the accumulation of potentially
      harmful substances such as advanced glycated end-products, protein kinase C, and
      nuclear factor kappaB, which are directly implicated in the development of
      vascular complications in diabetes. These adverse effects are not reversed when
      the high blood glucose is corrected, and some may be permanent because of
      epigenetic changes. Some antidiabetes drugs and antioxidant substances have
      produced partial reversibility of the mechanisms involved in the metabolic memory
      at the experimental level, but probably the best strategy is to optimize the
      metabolic control as early as possible, even before diabetes is diagnosed.

PMID- 22650228
TI  - Current knowledge and future directions on cardiovascular disease in diabetes.

PMID- 22650229
TI  - Sequential chemical bath deposition of Cu(2-x)Se/CdS film by suppressing ion
      exchange reaction.
AB  - Chemical bath deposition is an attractive technique to form single- and
      multilayered metal oxide/chalcogenide films on electrode surfaces. However, the
      occurrence of desorption and/or ion-exchange reaction during subsequent chemical
      bath deposition has so far limited preparation of multilayered metal
      oxide/chalcogenide films. In this paper, we report a method to prevent desorption
      and ion-exchange reaction of metal oxide/chalcogenide on electrode surfaces using
      a polyelectrolyte multilayer during sequential chemical bath deposition. By
      controlling the ion permeability of the polyelectrolyte multilayer, Cu(2-x)Se
      film was successfully deposited on the CdS film. The Cu(2-x)Se/CdS film is
      confirmed by UV-vis absorption spectroscopy, scanning electron microscopy, energy
      dispersive X-ray analysis, and X-ray powder diffractometer. Furthermore, the Cu(2
      x)Se/CdS films were investigated as photoinduced charge transfer devices which
      showed photocurrents of 0.22 mA/cm(2) under illumination (I = 100 mW/cm(2)).

PMID- 22650231
TI  - The associations between RAS mutations and clinical characteristics in follicular
      thyroid tumors: new insights from a single center and a large patient cohort.
AB  - BACKGROUND: Many studies on thyroid follicular tumors have reported the presence
      of somatic mutations to three forms of RAS: HRAS, KRAS, and NRAS. However, the
      frequency and clinical significance of these RAS mutations remain unclear, in
      large part due to the different methodologies being used for mutation analysis
      and the limited number of cases featured in studies. To clarify the significance
      of RAS mutations, we examined a large number of follicular adenomas and
      carcinomas obtained from a single institute using established methods for the
      analysis of RAS. METHODS: Tumor samples from 40 follicular adenoma and 58
      follicular carcinoma patients treated at the Kanagawa Cancer Center Hospital were
      analyzed. The three RAS mutations at codons 12 and 61 were assessed with a
      polymerase chain reaction-based loop-hybrid mobility shift assay followed by
      confirmation with direct sequencing. The relationships between mutation status
      and clinicopathological features at the time of the initial operation and the
      prognosis of the patients were also analyzed. RESULTS: Twelve out of 40 (30%)
      adenomas harbored RAS mutations. In contrast, 33 out of 58 (57%) follicular
      carcinomas harbored RAS mutations, and the mutation was predominantly found in
      the NRAS codon 61 (22/33, 67%, p<0.01). The rate of gene mutations was
      significantly higher in the carcinomas than in the adenomas (p<0.01). The NRAS
      codon 61 mutation in follicular carcinomas was positively associated with distant
      metastases through the entire clinical course of the patients (p<0.05), and RAS
      mutations were associated with poor overall patient survival (p<0.05).
      CONCLUSIONS: We investigated the frequency of RAS mutations in follicular thyroid
      tumors from a large number of cases obtained from a single institute. The
      predominance of NRAS codon 61 mutations as a feature of carcinomas indicates that
      the diagnosis of adenoma alongside the presence of this mutation should be made
      cautiously. Our study raises the possibility that follicular adenomas with the
      RAS mutations have an inherent malignant potential; however, the clinical
      significance of this finding should be further investigated in more patients and
      over a longer follow-up period.

PMID- 22650232
TI  - Temperature-controlled electrochemical switch based on layered double
      hydroxide/poly(N-isopropylacrylamide) ultrathin films fabricated via layer-by
      layer assembly.
AB  - In this paper we report the fabrication of layered double hydroxide (LDH)
      nanoparticles/poly(N-isopropylacrylamide) (pNIPAM) ultrathin films (UTFs) via the
      layer-by-layer assembly technique, and their switchable electrocatalytic
      performance in response to temperature stimuli was demonstrated. X-ray
      diffraction and UV-vis absorption spectroscopy indicate a periodic layered
      structure with uniform and regular growth of the (LDH/pNIPAM)(n) UTFs; an
      interaction based on hydrogen bonding between LDH nanoparticles and pNIPAM was
      confirmed by X-ray-photoelectron spectroscopy and Fourier transform infrared
      spectroscopy. Temperature-triggered cyclic voltammetry and electrochemical
      impedance spectroscopy switch for the UTFs was obtained between 20 and 40 
      degrees C, accompanied by reversible changes in surface topography and film
      thickness revealed by atomic force microscopy and ellipsometry, respectively. The
      electrochemical on-off property of the temperature-controlled (LDH/pNIPAM)(n)
      UTFs originates from the contraction-expansion configuration of pNIPAM with low
      high electrochemical impedance. In addition, a switchable electrocatalytic
      behavior of the (LDH/pNIPAM)(n) UTFs toward the oxidation of glucose was
      observed, resulting from the temperature-controlled charge transfer rate.
      Therefore, this work provides a facile approach for the design and fabrication of
      a well-ordered command interface with a temperature-sensitive property, which can
      be potentially applied in electrochemical sensors and switching.

PMID- 22650230
TI  - Imatinib enhances docetaxel-induced apoptosis through inhibition of nuclear
      factor-kappaB activation in anaplastic thyroid carcinoma cells.
AB  - BACKGROUND: We previously reported the partial effectiveness of imatinib (also
      known as STI571, Glivec, or Gleevec) on anaplastic thyroid cancer (ATC) cells.
      Imatinib is a selective tyrosine kinase inhibitor that has been used for various
      types of cancer treatments. Recently, several reports have demonstrated that
      imatinib enhanced the sensitivity of cancer cells to other anticancer drugs. In
      this study, therefore, we investigated whether imatinib enhances the antitumor
      activity of docetaxel in ATC cells. METHODS: Two ATC cell lines, FRO and KTC-2,
      were treated with imatinib and/or docetaxel. Cell survival assay and flow
      cytometry for annexin V were used to assess the induction of apoptosis. Changes
      of pro- and antiapoptotic factors were determined by Western blot. Nuclear factor
      kappaB (NF-kappaB) activity was measured by DNA-binding assay. Tumor growth was
      also investigated in vivo. RESULTS: The combined treatment significantly enhanced
      apoptosis compared with single treatment. ATC cells themselves expressed high
      levels of antiapoptotic factors, X-linked inhibitor of apoptosis (XIAP), and
      survivin. The treatment with docetaxel alone further increased their expressions;
      however, the combined treatment blocked the inductions. Although imatinib alone
      had no effect on NF-kappaB background levels, combined treatment significantly
      suppressed the docetaxel-induced NF-kappaB activation. Further, the combined
      administration of the drugs also showed significantly greater inhibitory effect
      on tumor growth in mice xenograft model. CONCLUSIONS: Imatinib enhanced antitumor
      activity of docetaxel in ATC cells. Docetaxel seemed to induce both pro- and
      antiapoptotic signaling pathways in ATC cells, and imatinib blocked the
      antiapoptotic signal. Thus, docetaxel combined with imatinib emerges as an
      attractive strategy for the treatment of ATC.

PMID- 22650233
TI  - Validation of analytical methods in GMP: the disposable Fast Read 102(r) device,
      an alternative practical approach for cell counting.
AB  - BACKGROUND: The quality and safety of advanced therapy products must be
      maintained throughout their production and quality control cycle to ensure their
      final use in patients. We validated the cell count method according to the
      International Conference on Harmonization of Technical Requirements for
      Registration of Pharmaceuticals for Human Use and European Pharmacopoeia,
      considering the tests' accuracy, precision, repeatability, linearity and range.
      METHODS: As the cell count is a potency test, we checked accuracy, precision, and
      linearity, according to ICH Q2. Briefly our experimental approach was first to
      evaluate the accuracy of Fast Read 102(r) compared to the Burker chamber. Once
      the accuracy of the alternative method was demonstrated, we checked the precision
      and linearity test only using Fast Read 102(r). The data were statistically
      analyzed by average, standard deviation and coefficient of variation percentages
      inter and intra operator. RESULTS: All the tests performed met the established
      acceptance criteria of a coefficient of variation of less than ten percent. For
      the cell count, the precision reached by each operator had a coefficient of
      variation of less than ten percent (total cells) and under five percent (viable
      cells). The best range of dilution, to obtain a slope line value very similar to
      1, was between 1:8 and 1:128. CONCLUSIONS: Our data demonstrated that the Fast
      Read 102(r) count method is accurate, precise and ensures the linearity of the
      results obtained in a range of cell dilution. Under our standard method
      procedures, this assay may thus be considered a good quality control method for
      the cell count as a batch release quality control test. Moreover, the Fast Read
      102(r) chamber is a plastic, disposable device that allows a number of samples to
      be counted in the same chamber. Last but not least, it overcomes the problem of
      chamber washing after use and so allows a cell count in a clean environment such
      as that in a Cell Factory. In a good manufacturing practice setting the
      disposable cell counting devices will allow a single use of the count chamber
      they can then be thrown away, thus avoiding the waste disposal of vital dye (e.g.
      Trypan Blue) or lysing solution (e.g. Tuerk solution).

PMID- 22650234
TI  - Network pharmacology for cancer drug discovery: are we there yet?

PMID- 22650235
TI  - From isolated hypotheses to connected practical studies: statisticians' role in a
      seamless targeted therapy development.

PMID- 22650237
TI  - Pharmaceutical structure montages as catalysts for design and discovery.
AB  - Majority of pharmaceuticals are small molecule organic compounds. Their
      structures are most effectively described and communicated using the graphical
      language of organic chemistry. A few years ago we decided to harness this
      powerful language to create new educational tools that could serve well for data
      mining and as catalysts for discovery. The results were the Top 200 drug posters,
      which we have posted online for everyone to enjoy and update yearly. This article
      details the origin and motivation for our design and highlights the value of this
      graphical format by presenting and analyzing a new pharmaceutical structure
      montage (poster) focused on US FDA approved drugs in 2011.

PMID- 22650238
TI  - Modulating metals as a therapeutic strategy for Alzheimer's disease.
AB  - In 1906, Alois Alzheimer first characterized the disease that bears his name.
      Despite intensive research, which has led to a better understanding of the
      pathology, there is no effective treatment for this disease. Of the drugs
      approved by the US FDA, none are disease modifying, only symptomatic.
      Unfortunately, there have been a number of failed clinical trials in the past 10
      years where studies show either no cognitive improvement or, worse, serious side
      effects associated with treatment. Hence, there is a need for the field to look
      at alternative approaches to therapy. In this review, we will discuss how metal
      dyshomeostasis occurs in aging and Alzheimer's disease. Concomitantly, we will
      discuss how targeting this dyshomeostasis offers an effective and novel
      therapeutic approach. Thus far, compounds that mediate these effects have shown
      great potential in both preclinical animal studies as well as in early-stage
      clinical trials.

PMID- 22650239
TI  - From multiply active natural product to candidate drug? Antibacterial (and other)
      minor groove binders for DNA.
AB  - Natural products that bind to DNA in the minor groove are valuable templates for
      drug design. Examples include distamycin, netropsin, duocarmycin and anthramycin.
      Anticancer and anti-infective drugs feature strongly amongst their derivatives.
      The structures and activities of chemotypes with various therapeutic actions are
      discussed in the context of the broader field of therapeutically active minor
      groove binders. The evolution of a series of exceptionally potent and nontoxic
      antibacterial compounds is discussed using the general design principle of
      introducing additional hydrophobicity into the distamycin template to increase
      the strength of binding to DNA. As well as potent antibacterial compounds,
      antifungal and antiparasitic compounds with exceptional cellular activity against
      trypanosomes have been identified. Possible mechanisms of action including gene
      regulation and topoisomerase inhibition are discussed with the need in mind to
      understand selective toxicity in the series to support future drug discovery.

PMID- 22650240
TI  - 5-azacytosine compounds in medicinal chemistry: current stage and future
      perspectives.
AB  - This review summarizes the basic milestones of the research of 5-azacytosine
      nucleosides chronologically from their discovery and anticancer activity
      identification, through to subsequent unveiling of their mechanism of action
      based on DNA hypomethylation and tumor-suppressor gene reactivation, to the final
      US FDA approval of 5-azacytidine (Vidaza((r))) and 2'-deoxy-5-azacytidine
      (Dacogen((r))) for the treatment of myelodysplastic syndromes. 5,6-dihydro-2'
      deoxy-5-azacytidine, a compound with anti-HIV activity through lethal
      mutagenesis, representing a unique mechanism of action among existing anti
      retroviral drugs, is discussed together with quite recent discovery of its so far
      unexpected hypomethylation activity. Special attention is paid to 5-azacytosine
      acyclic nucleoside analogues and phosphonomethyl derivatives with the emphasis on
      the new potent anti-DNA virus agent (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]
      5-azacytosine and its prodrug forms. Considering the potential pharmaceutical
      applications, 5-azacytosine and 5,6-dihydro-5-azacytosine appear to be so far the
      most effective cytosine mimics for the design of novel antiviral and anti-tumor
      drug candidates.

PMID- 22650241
TI  - The medicinal chemistry of stable synthetic leukotriene B(3) and B(4) analogues.
AB  - Leukotriene B(3) and B(4) are part of an important class of signaling molecules -
      the leukotrienes, implicated in the inflammation process. Their pro-inflammatory
      effects have been widely recognized for almost three decades but it is only
      recently that their benefit in host defense has begun to be acknowledged. Their
      use as therapeutic agents is, unfortunately, limited by rapid metabolism.
      However, over the past 25 years, a number of stable leukotriene B(3) and B(4)
      analogues have been produced. In this review, we examine their medicinal
      chemistry and biological evaluation.

PMID- 22650242
TI  - Medicinal chemistry of farnesoid X receptor ligands: from agonists and
      antagonists to modulators.
AB  - The nuclear receptor farnesoid X receptor (FXR) has emerged as a highly promising
      target in preclinical development in recent years. A significant amount of
      research has been conducted and, although none has reached clinical use, many
      synthetic ligands of FXR have been described. This review outlines the available
      knowledge regarding the medicinal chemistry and SAR of these FXR ligands, and
      discusses the molecular interactions of the compounds with the FXR ligand-binding
      domain by interpreting the existing co-crystal structures.

PMID- 22650244
TI  - A novel, unusually efficacious duocarmycin carbamate prodrug that releases no
      residual byproduct.
AB  - A unique heterocyclic carbamate prodrug of seco-CBI-indole(2) that releases no
      residual byproduct is reported as a new member of a class of hydrolyzable
      prodrugs of the duocarmycin and CC-1065 family of natural products. The prodrug
      was designed to be activated by hydrolysis of a carbamate releasing the free drug
      without the cleavage release of a traceable extraneous group. Unlike prior
      carbamate prodrugs examined that are rapidly cleaved in vivo, the cyclic
      carbamate was found to be exceptionally stable to hydrolysis under both chemical
      and biological conditions providing a slow, sustained release of the
      exceptionally potent free drug. An in vivo evaluation of the prodrug found that
      its efficacy exceeded that of the parent drug, that its therapeutic window of
      efficacy versus toxicity is much larger than the parent drug, and that its slow
      free drug release permitted the safe and efficacious use of doses 150-fold higher
      than the parent compound.

PMID- 22650245
TI  - Acetylphosphonate as a surrogate of acetate or acetamide in organocatalyzed
      enantioselective aldol reactions.
AB  - Highly enantioselective aldol reactions of acetylphosphonates and activated
      carbonyl compounds was realized with cinchona alkaloid derived catalysts, in
      which the acetylphosphonate was directly used as an enolate precursor for the
      first time. The aldol product obtained was converted in situ to its corresponding
      ester or amide through methanolysis or aminolysis. The overall process may be
      viewed as formal highly enantioselective acetate or acetamide aldol reactions,
      which are very difficult to achieve directly with organocatalytic methods.

PMID- 22650249
TI  - Ultrasensitive and selective recognition of peptide hormone using close-packed
      arrays of hPTHR-conjugated polymer nanoparticles.
AB  - Recognition of diverse hormones in the human body is a highly significant
      challenge because numerous diseases can be affected by hormonal imbalances.
      However, the methodologies reported to date for detecting hormones have exhibited
      limited performance. Therefore, development of innovative methods is still a
      major concern in hormone-sensing applications. In this study, we report an
      immobilization-based approach to facilitate formation of close-packed arrays of
      carboxylated polypyrrole nanoparticles (CPPyNPs) and their integration with human
      parathyroid hormone receptor (hPTHR), which is a B-class family of G-protein
      coupled receptors (GPCRs). Our devices enabled use of an electrically
      controllable liquid-ion-gated field-effect transistor by using the surrounding
      phosphate-buffered saline solution (pH 7.4) as electrolyte solution. Field
      induced signals from the peptide hormone sensors were observed and provided
      highly sensitive and selective recognition of target molecules at unprecedentedly
      low concentrations (ca. 48 fM). This hormone sensor also showed long-term
      stability and excellent selectivity in fetal bovine serum. Importantly, the
      hormone receptor attached on the surface of CPPyNPs enabled GPCR functional
      studies; synergistic effects corresponding to increased hPTH peptide length were
      monitored. These results demonstrate that close-packed CPPyNP arrays are a
      promising approach for high-performance biosensing devices.

PMID- 22650250
TI  - Unsedated peroral wireless pH capsule placement vs. standard pH testing: a
      randomized study and cost analysis.
AB  - BACKGROUND: Wireless capsule pH-metry (WC) is better tolerated than standard
      nasal pH catheter (SC), but endoscopic placement is expensive. AIMS: to confirm
      that non-endoscopic peroral manometric placement of WC is as effective and better
      tolerated than SC and to perform a cost analysis of the available esophageal pH
      metry methods. METHODS: Randomized trial at 2 centers. Patients referred for
      esophageal pH testing were randomly assigned to WC with unsedated peroral
      placement or SC after esophageal manometry (ESM). Primary outcome was overall
      discomfort with pH-metry. Costs of 3 different pH-metry strategies were analyzed:
      1) ESM + SC, 2) ESM + WC and 3) endoscopically placed WC (EGD + WC) using
      publicly funded health care system perspective. RESULTS: 86 patients (mean age 51
      +/- 2 years, 71% female) were enrolled. Overall discomfort score was less in WC
      than in SC patients (26 +/- 4 mm vs 39 +/- 4 mm VAS, respectively, p = 0.012) but
      there were no significant group differences in throat, chest, or overall
      discomfort during placement. Overall failure rate was 7% in the SC group vs 12%
      in the WC group (p = 0.71). Per patient costs ($Canadian) were $1475 for EGD +
      WC, $1014 for ESM + WC, and $906 for ESM + SC. Decreasing the failure rate of ESM
      + WC from 12% to 5% decreased the cost of ESM + WC to $991. The ESM + SC and ESM
      + WC strategies became equivalent when the cost of the WC device was dropped from
      $292 to $193. CONCLUSIONS: Unsedated peroral WC insertion is better tolerated
      than SC pH-metry both overall and during placement. Although WC is more costly,
      the extra expense is partially offset when the higher patient and caregiver time
      costs of SC are considered. TRIAL REGISTRATION: Clinicaltrials.gov Identifier
      NCT01364610.

PMID- 22650251
TI  - Spliced leader RNA silencing (SLS) - a programmed cell death pathway in
      Trypanosoma brucei that is induced upon ER stress.
AB  - Trypanosoma brucei is the causative agent of African sleeping sickness. The
      parasite cycles between its insect (procyclic form) and mammalian hosts
      (bloodstream form). Trypanosomes lack conventional transcription regulation, and
      their genes are transcribed in polycistronic units that are processed by trans
      splicing and polyadenylation. In trans-splicing, which is essential for
      processing of each mRNA, an exon, the spliced leader (SL) is added to all mRNAs
      from a small RNA, the SL RNA. Trypanosomes lack the machinery for the unfolded
      protein response (UPR), which in other eukaryotes is induced under endoplasmic
      reticulum (ER) stress. Trypanosomes respond to such stress by changing the
      stability of mRNAs, which are essential for coping with the stress. However,
      under severe ER stress that is induced by blocking translocation of proteins to
      the ER, treatment of cells with chemicals that induce misfolding in the ER, or
      extreme pH, trypanosomes elicit the spliced leader silencing (SLS) pathway. In
      SLS, the transcription of the SL RNA gene is extinguished, and tSNAP42, a
      specific SL RNA transcription factor, fails to bind to its cognate promoter. SLS
      leads to complete shut-off of trans-splicing. In this review, I discuss the UPR
      in mammals and compare it to the ER stress response in T. brucei leading to SLS.
      I summarize the evidence supporting the notion that SLS is a programmed cell
      death (PCD) pathway that is utilized by the parasites to substitute for the
      apoptosis observed in higher eukaryotes under prolonged ER stress. I present the
      hypothesis that SLS evolved to expedite the death process, and rapidly remove
      from the population unfit parasites that, by elimination via SLS, cause minimal
      damage to the parasite population.

PMID- 22650252
TI  - Stress cardiomyopathy (Tako-Tsubo) associated with sustained polymorphic
      ventricular tachycardia.
AB  - We present a case of 38-year-old woman with stress cardiomyopathy presenting to
      the emergency department with a 1-week history of recurrent syncope due to
      sustained polymorphic ventricular tachycardia.

PMID- 22650253
TI  - Using fragment-based technologies to target protein-protein interactions.
AB  - Whilst fragment-based screening has found significant utility in aiding the
      discovery of high quality hits against a range of targets, the use of this
      technology in the protein-protein interaction inhibitor field is very much in its
      infancy. This review aims to highlight the key technologies used to identify
      fragment hits, such as NMR, SPR, X-ray crystallography and biochemical screening,
      the fragment-based protein-protein interaction case studies reported to date and,
      more importantly, the potential of this methodology in unearthing high quality
      hit molecules in this critical area of drug discovery. In addition, we also
      discuss some of the key aspects of fragment library design, the composition of a
      high quality library and suggest ways in which future, more structurally diverse
      fragments which occupy different regions of chemical space to the vast majority
      of current fragment libraries may be selected.

PMID- 22650255
TI  - Protein-protein docking and hot-spot prediction for drug discovery.
AB  - Most processes in living organisms occur through an intricate network of protein
      protein interactions, in which any malfunctioning can lead to pathological
      situations. Therefore, current research in biomedicine is starting to focus on
      protein interaction networks. A detailed structural knowledge of these
      interactions at molecular level will be necessary for drug discovery targeting
      protein-protein interactions. The challenge from a structural biology point of
      view is determining the structure of the specific complex formed upon interaction
      of two or several proteins, and/or locating the surface residues involved in the
      interaction and identify which of them are the most important ones for binding
      (hot-spots). In this line, an increasing number of computer tools are available
      to complement experimental efforts. Docking algorithms can achieve successful
      predictive rates in many complexes, as shown in the community assessment
      experiment CAPRI, and have already been applied to a variety of cases of
      biomedical interest. On the other side, many methods for interface and hotspot
      prediction have been reported, based on a variety of evolutionary, geometrical
      and physico-chemical parameters. Computer predictions are reaching a significant
      level of maturity, and can be very useful to guide experiments and suggest
      mutations, or to provide a mechanistic framework to the experimental results on a
      given interaction. We will review here existing computer approaches for
      proteinprotein docking, interface prediction and hot-spot identification, with
      focus to drug discovery targeting protein-protein interactions.

PMID- 22650254
TI  - P53 mdm2 inhibitors.
AB  - The protein-protein interaction (PPI) between p53 and its negative regulator MDM2
      comprises one of the most important and intensely studied PPI's involved in
      preventing the initiation of cancer. The interaction between p53 and MDM2 is
      conformation-based and is tightly regulated on multiple levels. Due to the
      Angstrom level structural insight there is a reasonable understanding of the
      structural requirements needed for a molecule to bind to MDM2 and successfully
      inhibit the p53/MDM2 interaction. The current review summarizes the binding
      characteristics of the different disclosed small molecules for inhibition of MDM2
      with a co-crystal structure. Synthetic access to these compounds as well as their
      derivatives are described in detail.

PMID- 22650256
TI  - Small-molecule inhibitors of protein-protein interactions: how to mimic a protein
      partner.
AB  - This systematic review describes successful examples of small-molecule inhibitors
      of protein-protein interactions, and compares their binding strategies to those
      employed by the natural protein partners. It extends and updates an earlier
      survey of this type (Fry DC, Curr Prot Pep Sci 2008; 9: 240-7). From analysis of
      these systems, common themes and lessons are presented that may assist future
      drug discovery efforts involving targets in this class. One encouraging finding
      is that a wide scope appears to be allowed at these sites in terms of binding
      strategies and chemotypes, which suggests that the outlook for finding small
      molecule protein-protein inhibitors is favorable.

PMID- 22650257
TI  - Modulating protein-protein interactions: from structural determinants of binding
      to druggability prediction to application.
AB  - During the last decades, a large amount of evidence has been gathered on the
      importance of protein-protein interactions in tuning and regulating most
      important biological processes. Since many of these pathways are deeply involved
      in diseases, extensive research efforts have been undertaken towards the
      modulation of protein-protein interactions. At the early stage of this challenge
      most of the attention was drawn to the drawbacks of such a therapeutic approach.
      Encouragingly, however, several recent studies provided a proof of concept that
      protein-protein interactions are actually valuable targets and that they do have
      a promising therapeutic potential. This review is divided into three sections. In
      the first section we summarize the general features of protein-protein
      interfaces, focusing on the characteristics that make them different from
      classical protein-ligand binding sites, as well as on problematic aspects that
      hamper the application of classical drug discovery approaches. In the second
      section, we present how some of the characteristics of protein-protein
      interactions can be exploited fruitfully in drug design, hence focusing on the
      druggability of protein-protein interfaces. Methods successfully applied to
      protein-protein interactions will be introduced, giving special attention to the
      computational ones. In the third section, three case studies are presented.
      First, we describe protein-protein interaction modulators targeting HDM2 and the
      computational methods applied to identify them. Next, we present the
      retrospective application of the discussed approaches on the well-examined target
      IL-2. We conclude with a prospective application to the NHR2 protein, a target
      just recently validated experimentally with the aid of computational methods.

PMID- 22650258
TI  - Druggability of dynamic protein-protein interfaces.
AB  - The conformational flexibility of protein targets is being increasingly
      recognized in the drug discovery and design processes. When working on a
      particular disease-related biochemical pathway, it is of crucial importance to
      carefully select druggable protein binding pockets among all those cavities that
      may appear transiently or permanently on the respective protein surface. In this
      review, we will focus on the conformational dynamics of proteins that governs the
      formation and disappearance of such transient pockets on protein surfaces. We
      will also touch on the issue of druggability of transiently formed pockets. For
      example, protein cavities suitable to bind small drug-like molecules show an
      increased pocket size and buriedness when compared to empty sites. Interestingly,
      we observed in molecular dynamics simulations of five different protein systems
      that the conformational transitions on the protein surface occur almost
      barrierless and large pockets are found at similar frequencies as small pockets,
      see below. Thus, the dynamical processes at protein surfaces are better
      visualized as fluid-like motion than as energetically activated events. We
      conclude by comparing two computational tools, EPOS and MDpocket, for identifying
      transient pockets in PDK1 kinase. We illustrate how the obtained results depend
      on the way in which corresponding pockets in different molecular dynamics
      snapshots are connected to each other.

PMID- 22650259
TI  - Protein-protein interfaces integrated into interaction networks: implications on
      drug design.
AB  - The growing perception that diseases are often consequences of multiple molecular
      abnormalities rather than being the result of a single defect highlights the
      importance of network-centric view in therapeutic approaches. Protein interaction
      networks may contribute to understanding of disease, assist in drug design and
      discovery. Here, we review some recent advances in disease-associated protein
      interaction networks taking a structural approach. We first describe structural
      aspects of protein-protein interactions and properties of protein interfaces as
      related to drug design; we address protein interactions in a network perspective;
      in particular, we illustrate how integrating protein interfaces onto interaction
      networks can guide the identification of selective drug targets or drugs
      targeting multiple proteins in a network.

PMID- 22650261
TI  - Protein-protein interactions: network analysis and applications in drug
      discovery.
AB  - Physical interactions among proteins constitute the backbone of cellular
      function, making them an attractive source of therapeutic targets. Although the
      challenges associated with targeting protein-protein interactions (PPIs) -in
      particular with small molecules - are considerable, a growing number of
      functional PPI modulators is being reported and clinically evaluated. An
      essential starting point for PPI inhibitor screening or design projects is the
      generation of a detailed map of the human interactome and the interactions
      between human and pathogen proteins. Different routes to produce these biological
      networks are being combined, including literature curation and computational
      methods. Experimental approaches to map PPIs mainly rely on the yeast two-hybrid
      (Y2H) technology, which have recently shown to produce reliable protein networks.
      However, other genetic and biochemical methods will be essential to increase both
      coverage and resolution of current protein networks in order to increase their
      utility towards the identification of novel disease-related proteins and PPIs,
      and their potential use as therapeutic targets.

PMID- 22650260
TI  - A leap into the chemical space of protein-protein interaction inhibitors.
AB  - Protein-protein interactions (PPI) are involved in vital cellular processes and
      are therefore associated to a growing number of diseases. But working with them
      as therapeutic targets comes with some major hurdles that require substantial
      mutations from our way to design drugs on historical targets such as enzymes and
      G-Protein Coupled Receptor (GPCR). Among the numerous ways we could improve our
      methodologies to maximize the potential of developing new chemical entities on
      PPI targets, is the fundamental question of what type of compounds should we use
      to identify the first hits and among which chemical space should we navigate to
      optimize them to the drug candidate stage. In this review article, we cover
      different aspects on PPI but with the aim to gain some insights into the specific
      nature of the chemical space of PPI inhibitors. We describe the work of different
      groups to highlight such properties and discuss their respective approach. We
      finally discuss a case study in which we describe the properties of a set of 115
      PPI inhibitors that we compare to a reference set of 1730 enzyme inhibitors. This
      case study highlights interesting properties such as the unfortunate price that
      still needs to be paid by PPI inhibitors in terms of molecular weight,
      hydrophobicity, and aromaticity in order to reach a critical level of activity.
      But it also shows that not all PPI targets are equivalent, and that some PPI
      targets can demonstrate a better druggability by illustrating the better drug
      likeness of their associated inhibitors.

PMID- 22650262
TI  - Pharmacophore modelling as a virtual screening tool for the discovery of small
      molecule protein-protein interaction inhibitors.
AB  - Pharmacophore searches have become a popular tool for virtual screening of
      libraries to identify novel active substances that can be potentially developed
      into drugs. While they have been applied for years on common drug targets, their
      application in the discovery of protein-protein interaction inhibitors remains
      limited. This review describes current pharmacophore modelling methods applied in
      the discovery of novel inhibitors targeting protein-protein interactions. We
      first address the mimicry of protein-protein interactions with their respective
      inhibitors as observed in crystal structure complexes. This mimicry can be
      exploited to derive a pharmacophore query from protein-protein complex
      structures. We then discuss several cases where pharmacophore queries were
      utilized for the discovery of first-in-class inhibitors of their respective
      protein-protein interaction targets. These examples have demonstrated the
      usefulness of pharmacophore modelling in the quest for protein-protein
      interaction inhibitors.

PMID- 22650263
TI  - Editorial: Toward the design of drugs on protein-protein interactions.

PMID- 22650264
TI  - Cervical perivascular epithelioid cell tumour (PEComa) of the uterine cervix:
      cytological findings in a cervical smear.

PMID- 22650265
TI  - Potential energy mapping of the excited-states of (eta6-arene)Cr(CO)3 complexes:
      the evolution toward CO-loss or haptotropic shift processes.
AB  - The potential energy profiles of the optically accessible excited states of two
      model (eta(6)-arene)Cr(CO)(3) systems were explored using Time-Dependent Density
      Functional Theory. Two photochemical reactions were investigated, CO-loss and the
      haptotropic or ring-slip of the arene ligand. In both cases the photochemical
      reaction requires the surmounting of a small thermal barrier in the lowest energy
      excited state. In the case of (eta(6)-benzene)Cr(CO)(3) only one excited state is
      populated following 400 nm excitation and this leads to the release of CO. The
      calculated energy barrier to this process is 13 kJ mol(-1). In the case of
      (eta(6)-thiophenol)Cr(CO)(3) two excited states are accessible one leading to CO
      loss while the other results in the ring-slip process. The calculated barrier to
      the ring-slip process is 11 kJ mol(-1). The calculations are consistent with the
      results of picosecond time-resolved infrared studies.

PMID- 22650266
TI  - What prevents Struthio camelus and Dromaius novaehollandiae (Palaeognathae) from
      choking? A novel anatomical mechanism in ratites, the linguo-laryngeal apparatus.
AB  - BACKGROUND: The avian glottis channels air from the oropharynx to the trachea and
      is situated on an elevated structure, the laryngeal mound. It is imperative that
      the glottis be protected and closed during swallowing, which in mammals is
      achieved by covering the glottis with the epiglottis, as well as by adduction of
      the arytenoid cartilages. An epiglottis, however, is reportedly absent in birds.
      Ratites such as Struthio camelus and Dromaius novaehollandiae possess a very wide
      glottis in comparison to other birds. The question therefore arises as to how
      these large birds avoid inhalation of ingesta through a wide glottis, with
      apparently little protection, particularly as their feeding method involves
      throwing the food over the glottis to land in the proximal esophagus. RESULTS: In
      S. camelus when the glottis was closed and the tongue body retracted, the smooth
      tongue root became highly folded and the rostral portion of the laryngeal mound
      was encased by the pocket in the base of the ? - shaped tongue body. In this
      position the lingual papillae also hooked over the most rostral laryngeal
      projections. However, in D. novaehollandiae, retraction of the tongue body over
      the closed glottis resulted in the prominent, triangular tongue root sliding over
      the rostral portion of the laryngeal mound. In both S. camelus and D.
      novaehollandiae these actions resulted in the rostral portion of the laryngeal
      mound and weakest point of the adducted glottis being enclosed and stabilised.
      CONCLUSIONS: Only after conducting a comparative study between these two birds
      using fresh specimens did it become clear how specific morphological
      peculiarities were perfectly specialised to assist in the closure and protection
      of the wide glottis. We identify, describe and propose a unique anatomical
      mechanism in ratites, which may functionally replace an epiglottis; the linguo
      laryngeal apparatus.

PMID- 22650267
TI  - Mobilized peripheral blood stem cells compared with bone marrow from HLA
      identical siblings for reduced-intensity conditioning transplantation in acute
      myeloid leukemia in complete remission: a retrospective analysis from the Acute
      Leukemia Working Party of EBMT.
AB  - Reduced-intensity conditioning (RIC)-alloSCT is increasingly used for acute
      myelogenous leukemia. Limited data are available for the comparison of peripheral
      blood stem cells with bone marrow for RIC-alloSCT. We used the European Group for
      Blood and Marrow Transplantation (EBMT) ALWP data to compare the outcome of
      mobilized peripheral blood stem cells (PBSC) (n = 1430) vs. bone marrow (BM) (n =
      107) for acute myelogenous leukemia (AML) patients with complete remission that
      underwent RIC-alloSCT from compatible sibling donors. The leukemia features, the
      disease status, and the time from diagnosis were similar between the two groups.
      Engraftment was achieved in 99% and 93% in the PBSC and BM groups, respectively
      (P < 0.0001). The day of engraftment was significantly earlier for the PBSC vs.
      the BM group, 15 (1-59) and 19 (5-69), respectively (P < 0.001). Acute GVHD,
      severe GVHD (grade III-IV) and chronic GVHD did not differ between the groups.
      leukemia-free survival (LFS), relapse, and non-relapsed mortality (NRM) were 51
      +/- 2%, 32 +/- 1%, and 17 +/- 1% vs. 50 +/- 6%, 38 +/- 6%, and 12 +/- 3% for the
      PBSC and BM groups, respectively. Our results indicate faster engraftment, but no
      difference in GVHD, LFS, relapse, and NRM when comparing PBSC to BM grafts from
      sibling donors following RIC conditioning. This is the first study comparing PBSC
      to BM grafts in the RIC setting, analyzing a homogeneous population of patients
      with AML in remission. Whether PBSC should be preferred for advanced phases of
      the disease, where the outcome is dominated by relapse incidences, needs further
      investigation.

PMID- 22650268
TI  - Phosphate-catalyzed degradation of D-glucosone in aqueous solution is accompanied
      by C1-C2 transposition.
AB  - Pathways in the degradation of the C(6) 1,2-dicarbonyl sugar (osone) D-glucosone
      2 (D-arabino-hexos-2-ulose) in aqueous phosphate buffer at pH 7.5 and 37  degrees
      C have been investigated by (13)C and (1)H NMR spectroscopy with the use of
      singly and doubly (13)C-labeled isotopomers of 2. Unlike its 3-deoxy analogue, 3
      deoxy-D-glucosone (3-deoxy-D-erythro-hexos-2-ulose) (1), 2 does not degrade via a
      1,2-hydrogen shift mechanism but instead initially undergoes C1-C2 bond cleavage
      to yield d-ribulose 3 and formate. The latter bond cleavage occurs via a 1,3
      dicarbonyl intermediate initially produced by enolization at C3 of 2. However, a
      careful monitoring of the fates of the sketetal carbons of 2 during its
      conversion to 3 revealed unexpectedly that C1-C2 bond cleavage is accompanied by
      C1-C2 transposition in about 1 out of every 10 transformations. Furthermore, the
      degradation of 2 is catalyzed by inorganic phosphate (P(i)), and by the P(i)
      surrogate, arsenate. C1-C2 transposition was also observed during the degradation
      of the C(5) osone, D-xylosone (D-threo-pentose-2-ulose), showing that this
      transposition may be a common feature in the breakdown of 1,2-dicarbonyl sugars
      bearing an hydroxyl group at C3. Mechanisms involving the reversible formation of
      phosphate adducts to 2 are proposed to explain the mode of P(i) catalysis and the
      C1-C2 transposition. These findings suggest that the breakdown of 2 in vivo is
      probably catalyzed by P(i) and likely involves C1-C2 transposition.

PMID- 22650269
TI  - Preparation of novel W/O gel-emulsions and their application in the preparation
      of low-density materials.
AB  - A series of novel and stable water in oil (W/O) gel-emulsions was created by
      utilizing a new cholesteryl derivative, a low-molecular mass gelator (LMMGs), as
      a stabilizer. In the emulsions, n-heptane, n-octane, n-nonane, n-decane, tertiary
      butyl methacrylate (t-BMA), methyl methacrylate (MMA), or styrene can be used as
      a continuous phase, water as a dispersed phase, and the stabilizer in the
      continuous phase is only 2% (w/v). Importantly, the gel-emulsions could be
      prepared by simple agitation of the mixtures at room temperature, while heating,
      cooling, and addition of a cosolvent or other additional component are
      unnecessary. SEM and optical microscopy studies revealed the foam-like structures
      of the gel-emulsions. Rheological measurements demonstrated that the gel
      emulsions are mechanically stable and exhibit typical viscoelastic properties.
      Surprisingly, the storage modulus, G', and the yield stress of the gel-emulsions
      with the alkanes as continuous phase decrease along with increasing the volume
      ratio of the dispersed phase, water, a property different from those of
      conventional gel-emulsions reported in the literature. From the viewpoint of
      application, the gel-emulsions as prepared are superior to others due to their
      simplicity in preparation, less amount of stabilizer needed, and the nonionic
      nature of the stabilizer, which must benefit practical applications. Furthermore,
      porous polymer monoliths could be prepared by polymerizing gel-emulsions with
      organic monomers as a continuous phase.

PMID- 22650270
TI  - How positive and negative expectations shape the experience of visceral pain: an
      experimental pilot study in healthy women.
AB  - BACKGROUND: In order to elucidate placebo and nocebo effects in visceral pain, we
      analyzed the effects of positive and negative expectations on rectal pain
      perception, rectal pain thresholds, state anxiety and cortisol responses in
      healthy women. METHODS: Painful rectal distensions were delivered at baseline,
      following application of an inert substance combined with either positive
      instructions of pain relief (placebo group, N = 15), negative instructions of
      pain increase (nocebo group, N = 17), or neutral instructions (control, N = 15).
      Perceived pain intensity, unpleasantness/aversion and urge-to-defecate, state
      anxiety and serum cortisol were determined at baseline, immediately following
      group-specific instructions and on a second study day after the same instructions
      (test day). Rectal pain thresholds were determined at baseline and on the test
      day. KEY RESULTS: Whereas perceived pain intensity was significantly decreased in
      the placebo group, the nocebo group revealed significantly increased pain
      intensity ratings, along with significantly greater anticipatory anxiety on the
      test day (all P < 0.05 vs controls). Cortisol concentrations were significantly
      increased in the nocebo group following treatment but not on the test day.
      CONCLUSIONS & INFERENCES: The experience of abdominal pain can be experimentally
      increased or decreased by inducing positive or negative expectations. Nocebo
      effects involve a psychological stress response, characterized by increased
      anticipatory anxiety. These findings further underscore the role of cognitive and
      emotional factors in the experience of visceral pain, which has implications for
      the pathophysiology and treatment of patients with chronic abdominal complaints.

PMID- 22650303
TI  - Proliferative human cell sources applied as biocomponent in bioartificial livers:
      a review.
AB  - INTRODUCTION: Bioartificial livers (BALs) are urgently needed to bridge severe
      liver failure patients to liver transplantation or liver regeneration. When based
      on primary hepatocytes, their efficacy has been shown in animal experiments and
      their safety was confirmed in clinical trials. However, a proliferative human
      cell source with therapeutic functionality is needed to secure availability and
      move BAL application forward. AREAS COVERED: This review compares the performance
      of BALs based on proliferative human biocomponents and primary hepatocytes. This
      review evaluates relevant studies identified by searching the MEDLINE database
      until July 2011 and some of our own unpublished data. EXPERT OPINION: All the
      discussed hepatocyte-like biocomponents show deficiencies in their hepatic
      functionality compared with primary hepatocytes, particularly functions occurring
      late in liver development. Nonetheless, the HepaRG, HepG2-GS-CYP3A4, and
      mesenchymal stem cells show efficacy in a statistically well-powered animal model
      of acute liver failure, when applied in a BAL device. Various methods to gain
      higher functionality of BALs, including genetic modification, the usage of
      combinatory cell sources, and improvement of culture methods, have scarcely been
      applied, but may further pave the path for BAL application. Clinical
      implementation of a BAL based on a human proliferative biocomponent is still
      several years away.

PMID- 22650304
TI  - Pathways linking temperament and depressive symptoms: a short-term prospective
      diary study among adolescents.
AB  - The current study examined mechanisms through which trait negative affectivity
      (NA) and effortful control (EC) prospectively predict increases in depressive
      symptoms in a community sample of 110 adolescents (mean age=16.40 years) in a 9
      week, multi-wave diary study. We hypothesised youth with high NA and low EC would
      experience greater increases in depressive symptoms because they generate more
      maladaptive cognitive responses to stress. NA predicted greater event-specific
      rumination and negative cognitive style across the study period. After
      controlling for trait cognitive vulnerabilities, only event-specific rumination
      mediated the effect of NA on subsequent depressive symptoms, suggesting that high
      NA youth are more likely to ruminate about stressful events, which then predicts
      increases in depressive symptoms. EC did not moderate the effects of NA on either
      depressive symptoms or cognitive responses to stress. Results are discussed in
      terms of vulnerability-stress models linking temperament and depressive symptoms
      in adolescence.

PMID- 22650307
TI  - Using Cross-links to Study Ribosomal Dynamics.
AB  - Abstract   After publications of 3-D models of a static ribosome and its large
      and small subunits, one of the next tasks is to recognize movable ribosomal
      elements responsible for mechanical shifts during protein synthesis. Statistic
      analysis of available cross-linking data allowed us to reveal three well
      separated groups of motions in the ribosome: I, mean magnitude of 10A; II, most
      abundant, centered at 20A and of wide dispersion, and III, sparsely populated,
      with large distances up to 95A. The last group, III, comprises elements, like the
      L7/12-stalk and the L1- protuberance, that adopt different positions in
      crystallographic or electron micrographic structures, and neighboring hairpins 88
      and 89, indicating mobility. We demonstrate that the cross- linking method can be
      applied to study ribosomal dynamics, including large-scale functional movements
      and, in particular, to estimate which structures participate in molecular
      switches.

PMID- 22650305
TI  - Diphenylpyridylethanamine (DPPE) derivatives as cholesteryl ester transfer
      protein (CETP) inhibitors.
AB  - A series of diphenylpyridylethanamine (DPPE) derivatives was identified
      exhibiting potent CETP inhibition. Replacing the labile ester functionality in
      the initial lead 7 generated a series of amides and ureas. Further optimization
      of the DPPE series for potency resulted in the discovery of cyclopentylurea 15d,
      which demonstrated a reduction in cholesterol ester transfer activity (48% of
      predose level) in hCETP/apoB-100 dual transgenic mice. The PK profile of 15d was
      suboptimal, and further optimization of the N-terminus resulted in the discovery
      of amide 20 with an improved PK profile and robust efficacy in transgenic
      hCETP/apoB-100 mice and in hamsters. Compound 20 demonstrated no significant
      changes in either mean arterial blood pressure or heart rate in telemeterized
      rats despite sustained high exposures.

PMID- 22650309
TI  - Real-time observation of polymer network formation by liquid- and solid-state NMR
      revealing multistage reaction kinetics.
AB  - The reaction rate for the end-cross-linking process of vinyl-terminated
      poly(dimethylsiloxane) by a cross-linker with four Si-H functionalities in the
      presence of solvent was studied by (1)H liquid-state NMR in dependence of the
      reaction temperature. The properties of the resulting polymer networks, i.e., the
      gel-point and the formation of the elastically effective network, were monitored
      in situ during the reaction by single-evolution-time (1)H double-quantum (SET-DQ)
      low-field NMR. It was found that the cross-linking kinetics shows no uniform
      reaction order for the conversions of the functional groups before the
      topological gelation threshold of the polymer network. The two NMR methods are
      combined to investigate the formation of the elastically effective network in
      dependence of the conversion of the functional groups of the precursor polymers
      and the cross-linker. The high chemical and time resolution of the experiments
      enabled an in-depth analysis of the reaction kinetics, allowing us to conclude on
      a multistage model for PDMS network formation by hydrosilylation-based end
      linking in the presence of solvent. We found that the nonuniform network
      formation kinetics originates from a dependence of the apparent reaction rate on
      the number of the Si-H groups of the cross-linker that have already reacted
      during the progress of the reaction. The fastest overall reaction rate is
      observed in a range until each cross-linker has reacted once on average, and a
      uniform apparent overall reaction order of unity with respect to cross-linker
      concentration is only found at a later stage, when multiply reacted cross-linker
      molecules with similar reactivity dominate.

PMID- 22650308
TI  - Quantification of biventricular myocardial function using cardiac magnetic
      resonance feature tracking, endocardial border delineation and echocardiographic
      speckle tracking in patients with repaired tetralogy of Fallot and healthy
      controls.
AB  - BACKGROUND: Parameters of myocardial deformation have been suggested to be
      superior to conventional measures of ventricular function in patients with
      tetralogy of Fallot (ToF), but have required non-routine, tagged cardiovascular
      magnetic resonance (CMR) techniques. We assessed biventricular myocardial
      function using CMR cine-based feature tracking (FT) and compared it to speckle
      tracking echocardiography (STE) and to simple endocardial border delineation
      (EBD). In addition, the relation between parameters of myocardial deformation and
      clinical parameters was assessed. METHODS: Overall, 28 consecutive adult patients
      with repaired ToF (age 40.4 +/- 13.3 years) underwent standard steady-state-free
      precession sequence CMR, echocardiography, and cardiopulmonary exercise testing.
      In addition, 25 healthy subjects served as controls. Myocardial deformation was
      assessed by CMR based FT (TomTec Diogenes software), CMR based EBD (using custom
      written software) and STE (TomTec Cardiac Performance Analysis software).
      RESULTS: Feature tracking was feasible in all subjects. A close agreement was
      found between measures of global left (LV) and right ventricular (RV) global
      strain. Interobserver agreement for FT and STE was similar for longitudinal LV
      global strain, but FT showed better inter-observer reproducibility than STE for
      circumferential or radial LV and longitudinal RV global strain. Reproducibility
      of regional strain on FT was, however, poor. The relative systolic length change
      of the endocardial border measured by EBD yielded similar results to FT global
      strain. Clinically, biventricular longitudinal strain on FT was reduced compared
      to controls (P < 0.0001) and was related to the number of previous cardiac
      operations. In addition, FT derived RV strain was related to exercise capacity
      and VE/VCO2-slope. CONCLUSIONS: Although neither the inter-study reproducibility
      nor accuracy of FT software were investigated, and its inter-observer
      reproducibility for regional strain calculation was poor, its calculations of
      global systolic strain showed similar or better inter-oberver reproducibility
      than those by STE, and could be applied across RV image regions inaccessible to
      echo. 'Global strain' calculated by EBD gave similar results to FT. Measurements
      made using FT related to exercise tolerance in ToF patients suggesting that the
      approach could have clinical relevance and deserves further study.

PMID- 22650310
TI  - Surface modification with alginate-derived polymers for stable, protein
      repellent, long-circulating gold nanoparticles.
AB  - Poly(ethylene) glycol is commonly used to stabilize gold nanoparticles (GNPs). In
      this study, we evaluated the ability of cysteine-functionalized alginate-derived
      polymers to both provide colloidal stability to GNPs and avoid recognition and
      sequestration by the body's defense system. These polymers contain multiple
      reactive chemical groups (hydroxyl and carboxyl groups) that could allow for
      ready functionalization with, for example, cell-targeting ligands and therapeutic
      drugs. We report here that alginate-coupled GNPs demonstrate enhanced stability
      in comparison with bare citrate-coated GNPs and a similar lack of interaction
      with proteins in vitro and long in vivo circulation as PEG-coated GNPs.

PMID- 22650311
TI  - Low defibrillation threshold in a patient with a dual-coil defibrillator lead
      implanted through a persistent left superior vena cava.
AB  - Several reports have described the successful insertion of implantable
      cardioverter defibrillator (ICD) in patients with a persistent left superior vena
      cava (PLSVC). The implanters have used various techniques to achieve appropriate
      lead placement. In our case, the use of a long sheath, guided by a deflectable
      catheter, not only facilitated proper implantation of the lead, but also provided
      a unique position of the dual-coil lead. This resulted in a very low
      defibrillation threshold (DFT). We describe a case of a patient found to have a
      PLSVC at implant who after successful insertion of the ICD exhibited DFT <= 5 J.

PMID- 22650318
TI  - Theoretical study of the thermal decomposition of the 5-methyl-2-furanylmethyl
      radical.
AB  - The thermal decomposition of the 5-methyl-2-furanylmethyl radical (R(1)), the
      most important primary radical formed during the combustion and thermal
      decomposition of 2,5-dimethylfuran (a promising next-generation biofuel), was
      studied using CBS-QB3 calculations and master equation (ME)/RRKM modeling.
      Because very little information is available in the literature, the detailed
      potential energy surface (PES) was investigated thoroughly. Only the main
      pathways, having a kinetic influence on the decomposition of R(1), were retained
      in the final ME/RRKM model. Among all the channels studied, the ring-opening of
      the 5-methyl-2-furanylmethyl radical, followed by ring enlargement to form
      cyclohexadienone molecules is predicted to be the easiest decomposition channel
      of R(1). The C(6) cyclic species formed can undergo unimolecular reactions to
      yield phenol and to a lesser extent cyclopentadiene and CO. Our calculations
      predict that these species are important products formed during the pyrolysis of
      2,5-dimethylfuran (DMF). Other channels involved in the decomposition of R(1)
      lead directly to the formation of linear and cyclic unsaturated C(5) species and
      constitute an additional source of cyclopentadiene and CO. High-pressure limit
      rate constants were computed as well as thermochemical properties for important
      species. ME/RRKM analysis was performed to probe the influence of pressure on the
      rate coefficients and pressure dependent rate coefficients were proposed for
      pressures and temperatures ranging, respectively, from 10(-2) bar to 10 bar and
      1000 to 2000 K.

PMID- 22650317
TI  - Aloe vera in the treatment for oral submucous fibrosis - a preliminary study.
AB  - BACKGROUND AND OBJECTIVES: Oral submucous fibrosis (OSMF) is a potentially
      malignant disorder of the oral mucosa, mainly associated with the practice of
      chewing gutka and betel quid. The pathogenesis is obscure, and till date, no
      definitive therapy is available for the management of OSMF. Hence, this
      preliminary study was carried out to compare the efficacy of Aloe vera with
      antioxidants in the treatment for OSMF. METHODS: Twenty study subjects with OSMF
      were included in the study. Patients were divided into two groups. There were 10
      patients in each group; group A subjects received 5 mg of aloe vera gel to be
      applied topically three times daily for 3 months and group B subjects received
      antioxidant capsules twice daily for 3 months. The results were analyzed with
      paired 't' test and unpaired 't' test. RESULTS: Aloe vera responded better in all
      the parameters assessed and responded in all the clinicohistopathological stages
      particularly in those with mild-stage clinically and early-stage
      histopathologically. Aloe vera showed a statistically significant reduction in
      burning sensation (P = 0.008), improvement in mouth opening (P = 0.02), and cheek
      flexibility (P = 0.01) on comparing with the antioxidant group. INTERPRETATION
      AND CONCLUSION: Overall assessment of the parameters depicted that Aloe vera
      group showed a better treatment response compared to the antioxidants group. It
      reduces the burning sensation and improves mouth opening thereby enhanced the
      patients' compliance. It proves to be a relatively safe, can be applied
      topically, easily available, economical, noninvasive, and efficacious in the
      treatment for OSMF.

PMID- 22650316
TI  - A unified phylogeny-based nomenclature for histone variants.
AB  - Histone variants are non-allelic protein isoforms that play key roles in
      diversifying chromatin structure. The known number of such variants has greatly
      increased in recent years, but the lack of naming conventions for them has led to
      a variety of naming styles, multiple synonyms and misleading homographs that
      obscure variant relationships and complicate database searches. We propose here a
      unified nomenclature for variants of all five classes of histones that uses
      consistent but flexible naming conventions to produce names that are informative
      and readily searchable. The nomenclature builds on historical usage and
      incorporates phylogenetic relationships, which are strong predictors of structure
      and function. A key feature is the consistent use of punctuation to represent
      phylogenetic divergence, making explicit the relationships among variant subtypes
      that have previously been implicit or unclear. We recommend that by default new
      histone variants be named with organism-specific paralog-number suffixes that
      lack phylogenetic implication, while letter suffixes be reserved for structurally
      distinct clades of variants. For clarity and searchability, we encourage the use
      of descriptors that are separate from the phylogeny-based variant name to
      indicate developmental and other properties of variants that may be independent
      of structure.

PMID- 22650319
TI  - Single-molecule Forster resonance energy transfer reveals an innate fidelity
      checkpoint in DNA polymerase I.
AB  - Enzymatic reactions typically involve complex dynamics during substrate binding,
      conformational rearrangement, chemistry, and product release. The noncovalent
      steps provide kinetic checkpoints that contribute to the overall specificity of
      enzymatic reactions. DNA polymerases perform DNA replication with outstanding
      fidelity by actively rejecting noncognate nucleotide substrates early in the
      reaction pathway. Substrates are delivered to the active site by a flexible
      fingers subdomain of the enzyme, as it converts from an open to a closed
      conformation. The conformational dynamics of the fingers subdomain might also
      play a role in nucleotide selection, although the precise role is currently
      unknown. Using single-molecule Forster resonance energy transfer, we observed
      individual Escherichia coli DNA polymerase I (Klenow fragment) molecules
      performing substrate selection. We discovered that the fingers subdomain actually
      samples through three distinct conformations--open, closed, and a previously
      unrecognized intermediate conformation. We measured the overall dissociation rate
      of the polymerase-DNA complex and the distribution among the various
      conformational states in the absence and presence of nucleotide substrates, which
      were either correct or incorrect. Correct substrates promote rapid progression of
      the polymerase to the catalytically competent closed conformation, whereas
      incorrect nucleotides block the enzyme in the intermediate conformation and
      induce rapid dissociation from DNA. Remarkably, incorrect nucleotide substrates
      also promote partitioning of DNA to the spatially separated 3'-5' exonuclease
      domain, providing an additional mechanism to prevent misincorporation at the
      polymerase active site. These results reveal the existence of an early innate
      fidelity checkpoint, rejecting incorrect nucleotide substrates before the enzyme
      encloses the nascent base pair.

PMID- 22650320
TI  - Feasibility and effects of patient-cooperative robot-aided gait training applied
      in a 4-week pilot trial.
AB  - BACKGROUND: Functional training is becoming the state-of-the-art therapy approach
      for rehabilitation of individuals after stroke and spinal cord injury. Robot
      aided treadmill training reduces personnel effort, especially when treating
      severely affected patients. Improving rehabilitation robots towards more patient
      cooperative behavior may further increase the effects of robot-aided training.
      This pilot study aims at investigating the feasibility of applying patient
      cooperative robot-aided gait rehabilitation to stroke and incomplete spinal cord
      injury during a therapy period of four weeks. Short-term effects within one
      training session as well as the effects of the training on walking function are
      evaluated. METHODS: Two individuals with chronic incomplete spinal cord injury
      and two with chronic stroke trained with the Lokomat gait rehabilitation robot
      which was operated in a new, patient-cooperative mode for a period of four weeks
      with four training sessions of 45 min per week. At baseline, after two and after
      four weeks, walking function was assessed with the ten meter walking test.
      Additionally, muscle activity of the major leg muscles, heart rate and the Borg
      scale were measured under different walking conditions including a non
      cooperative position control mode to investigate the short-term effects of
      patient-cooperative versus non-cooperative robot-aided gait training. RESULTS:
      Patient-cooperative robot-aided gait training was tolerated well by all subjects
      and performed without difficulties. The subjects trained more actively and with
      more physiological muscle activity than in a non-cooperative position-control
      mode. One subject showed a significant and relevant increase of gait speed after
      the therapy, the three remaining subjects did not show significant changes.
      CONCLUSIONS: Patient-cooperative robot-aided gait training is feasible in
      clinical practice and overcomes the main points of criticism against robot-aided
      gait training: It enables patients to train in an active, variable and more
      natural way. The limited number of subjects in this pilot trial does not permit
      valid conclusions on the effect of patient-cooperative robot-aided gait training
      on walking function. A large, possibly multi-center randomized controlled
      clinical trial is required to shed more light on this question.

PMID- 22650322
TI  - Steroid-sparing effects of angiotensin-II inhibitors in glioblastoma patients.
AB  - BACKGROUND: The standard of care in patients with glioblastoma (GBM) relies on
      surgical resection, radiation therapy (RT), and temozolomide. Steroids are
      required in almost all patients to reduce peritumoral edema, but are associated
      with numerous side effects. Vascular endothelial growth factor (VEGF) is a key
      driver of peritumoral edema and angiogenesis in human GBM. Recently, angiotensin
      II inhibitors were reported to reduce VEGF secretion and tumor growth in some
      animal models. METHODS: To investigate whether angiotensin-II inhibitors might
      have a similar effect in humans and before undertaking a prospective study, we
      retrospectively investigated a series of 87 consecutive, newly diagnosed GBM
      patients, treated in a single center. Amongst these patients, 29 (33%) were
      already treated before RT for high blood pressure (HBP), 18 of them (21%) with an
      angiotensin-II inhibitor. In all patients, performance status, surgical
      procedures, and steroid dosages were documented. RESULTS: Patients treated with
      angiotensin-II inhibitors, but not other antihypertensive drugs, required half of
      the steroids of the other patients during radiotherapy (P = 0.005 in multivariate
      analysis, considering other antihypertensive treatments, surgical resection, and
      performance status). This effect of angiotensin-II inhibitors was also
      significant at the beginning of radiotherapy (P = 0.03 in multivariate analysis).
      Treatment with angiotensin-II inhibitors had no effect on survival (16.2 vs. 17.9
      months for the treated and the non-treated group, respectively, P = 0.77).
      CONCLUSION: Angiotensin-II inhibitors might display significant steroid-sparing
      effects in brain tumor patients. Given the morbidity associated with steroids,
      this finding might have important practical consequences in these patients and
      warrants a randomized study.

PMID- 22650321
TI  - Macrolide-resistant Mycoplasma pneumoniae in adolescents with community-acquired
      pneumonia.
AB  - BACKGROUND: Although the prevalence of macrolide-resistant Mycoplasma pneumoniae
      isolates in Japanese pediatric patients has increased rapidly, there have been no
      reports concerning macrolide-resistant M. pneumoniae infection in adolescents
      aged 16 to 19 years old. The purpose of this study was to clarify the prevalence
      and clinical characteristics of macrolide-resistant M. pneumoniae in adolescent
      patients with community-acquired pneumonia. METHODS: A total of 99 cases with M.
      pneumoniae pneumonia confirmed by polymerase chain reaction (PCR) and culture
      were analyzed. Forty-five cases were pediatric patients less than 16 years old,
      26 cases were 16 to 19-year-old adolescent patients and 28 cases were adult
      patients. Primers for domain V of 23S rRNA were used and DNA sequences of the PCR
      products were compared with the sequence of an M. pneumoniae reference strain.
      RESULTS: Thirty of 45 pediatric patients (66%), 12 of 26 adolescent patients
      (46%) and seven of 28 adult patients (25%) with M. pneumoniae pneumonia were
      found to be infected with macrolide-resistant M. pneumoniae (MR patients).
      Although the prevalence of resistant strains was similar in pediatric patients
      between 2008 and 2011, an increase in the prevalence of resistant strains was
      observed in adolescent patients. Among 30 pediatric MR patients, 26 had an A-to-G
      transition at position 2063 (A2063G) and four had an A-to-G transition at
      position 2064 (A2064G). In 12 adolescent MR patients, 10 showed an A2063G
      transition and two showed an A2064G transition, and in seven adult MR patients,
      six showed an A2063G transition and one showed an A2064G transition. CONCLUSIONS:
      The prevalence of macrolide-resistant M. pneumoniae is high among adolescent
      patients as well as pediatric patients less than 16-years old. To prevent
      outbreaks of M. pneumoniae infection, especially macrolide-resistant M.
      pneumoniae, in closed populations including among families, in schools and in
      university students, physicians should pay close attention to macrolide-resistant
      M. pneumoniae.

PMID- 22650323
TI  - Thermodynamic analysis of ordered and disordered monolayer of argon adsorption on
      graphite.
AB  - We presented a detailed thermodynamic analysis of argon adsorption on a
      graphitized carbon black with a kinetic Monte Carlo scheme. In this study, we
      particularly paid attention to the formation of a hexagonal two-dimensional
      molecular layer on a graphite surface and discuss conditions of its stability and
      thermodynamic properties of the adsorbed phase as a function of loading. It is
      found that the simulation results are substantially affected by the dimensions of
      the simulation box when the monolayer forms a hexagonal ordered structure. This
      is due to the fact that the lattice constant is constrained by the dimensions of
      the surface. To circumvent this, we presented a thermodynamic technique, which
      allows for the variation of the box size as a function of loading, to determine
      the "intrinsic" lattice constant (rather than apparent average value because of
      the fixed dimensions of the simulation box) and the thermodynamic functions for
      the adsorbed phase: the Helmholtz free energy, the chemical potential, and the
      surface tension. The tangential and normal pressures as a function of the
      distance from the surface are also discussed.

PMID- 22650325
TI  - Small molecule inhibitors of signal transducer and activator of transcription 3
      (Stat3) protein.

PMID- 22650324
TI  - Exon skipping for nonsense mutations in Duchenne muscular dystrophy: too many
      mutations, too few patients?
AB  - INTRODUCTION: Duchenne muscular dystrophy (DMD), one of the most common and
      lethal genetic disorders, is caused by mutations of the dystrophin gene. Removal
      of an exon or of multiple exons using antisense molecules has been demonstrated
      to allow synthesis of truncated 'Becker muscular dystrophy-like' dystrophin.
      AREAS COVERED: Approximately 15% of DMD cases are caused by a nonsense mutation.
      Although patient databases have previously been surveyed for applicability to
      each deletion mutation pattern, this is not so for nonsense mutations. Here, we
      examine the world-wide database containing notations for more than 1200 patients
      with nonsense mutations. Approximately 47% of nonsense mutations can be
      potentially treated with single exon skipping, rising to 90% with double exon
      skipping, but to reach this proportion requires the development of exon skipping
      molecules targeting some 68 of dystrophin's 79 exons, with patient numbers spread
      thinly across those exons. In this review, we discuss progress and remaining
      hurdles in exon skipping and an alternative strategy, stop-codon readthrough.
      EXPERT OPINION: Antisense-mediated exon skipping therapy is targeted highly at
      the individual patient and is a clear example of personalized medicine. An
      efficient regulatory path for drug approval will be a key to success.

PMID- 22650326
TI  - Safety and clinical pharmacokinetics of nemonoxacin, a novel non-fluorinated
      quinolone, in healthy Chinese volunteers following single and multiple oral
      doses.
AB  - BACKGROUND: Nemonoxacin, a novel C-8-methoxy non-fluorinated quinolone, is
      currently being developed in oral and intravenous formulations. It exhibits
      potent antibacterial activities against Gram-positive, Gram-negative and atypical
      pathogens, especially methicillin-resistant Staphylococcus aureus. The first-in
      human study of a nemonoxacin capsule was conducted in a Western population. This
      current study was the first investigation on the clinical pharmacokinetics (PK)
      of nemonoxacin in a Chinese population, and was designed to determine PK data in
      a Chinese population and investigate the dose regimen for future clinical use.
      OBJECTIVE: The objective of this study was to evaluate the PK profile of
      nemonoxacin as well as its safety and tolerability in healthy Chinese volunteers
      following single and multiple oral doses. METHODS: The first part of the study
      was a double-blind, placebo-controlled, sequential ascending single-dose safety
      and tolerability study. In each cohort, two subjects received a placebo and six
      received single oral doses of nemonoxacin 125, 250, 500, 750 or 1000 mg. In the
      second part, the single-dose PK study, three dose levels (250, 500 and 750 mg) of
      nemonoxacin were administered orally to 12 healthy Chinese volunteers (male :
      female = 1 : 1) under fasting conditions in a crossover manner. The same
      volunteers received orally an additional dose of 500 mg under fed conditions
      after a 7-day washout. In the third part, the multiple-dose PK study, 24 subjects
      received 500 or 750 mg of nemonoxacin orally once daily for 10 consecutive days.
      Within each cohort, 12 subjects (male : female = 1 : 1) received the same dose
      level of nemonoxacin under fasting conditions. The PK profiles, safety and
      tolerability, and food and sex effects were evaluated. RESULTS: No severe or
      serious adverse events (AEs) occurred in this study, and no clinically
      significant abnormalities were noted in the vital signs or on physical
      examination. Notable AEs, mainly nausea and rash with or without pruritus, were
      mild and resolved spontaneously. Most laboratory AEs were mild and transient and
      the subjects recovered without treatment. Nemonoxacin was found to be rapidly
      absorbed, with peak plasma concentrations (C(max)) attained 1-2 hours after
      administration. The C(max) and area under the concentration-time curve from time
      zero to infinity (AUC(infinity)) were dose-proportional after single oral doses.
      The elimination half-life was 10-12 hours. Nemonoxacin was excreted primarily in
      urine, with a recovery of intact nemonoxacin of 60-70% of the dose over 72 hours.
      Food had a significant effect on the rate and extent of absorption (p < 0.001),
      increasing the time to reach C(max) from 1.14 to 3.64 hours and reducing C(max)
      by 34% and AUC(infinity) by 18%, while a sex effect was not found. C(max) and
      AUC(infinity) were similar between the single-dose and multiple-dose PK studies.
      The multiple-dose PK data suggested no drug accumulation in healthy subjects.
      CONCLUSION: Nemonoxacin exhibited a linear PK profile in the 250-750 mg dose
      range with moderate food effects. There was no accumulation following consecutive
      administration for 10 days. The PK and safety profiles of nemonoxacin in Chinese
      subjects support evaluation of once-daily dosing in the future development of
      this agent.

PMID- 22650351
TI  - Usability and feasibility of smartphone video capabilities for telehealth care in
      the U.S. military.
AB  - The two-way audio/visual capabilities on the latest smartphone platforms bring
      new possibilities for the delivery of healthcare services to users. Because this
      technology is so new, the feasibility and the basic usability of the technology
      need to be evaluated before more research is conducted on its application in the
      telehealth field. The purpose of this study was to conduct preliminary usability
      testing of smartphone two-way video capabilities for potential telehealth use for
      U.S. military service members. Seven service member volunteers communicated with
      research staff at a large military installation via Apple's (Cupertino, CA)
      FaceTime(r) app on the iPhone(r) 4 smartphone platform and conducted basic
      usability testing of the technology. Preferences for potential use of the
      technology were also assessed. The results showed that the technology has both
      limitations as well as potential for telehealth applications that warrant
      additional research.

PMID- 22650350
TI  - Scared stiff: the influence of anxiety on the perception of action capabilities.
AB  - Influences on the perception of affordances (i.e., opportunities for actions)
      have been primarily studied by manipulating the functional morphology of the
      body. However, affordances are not just determined by the functional morphology
      of the perceiver, but also by the physiological state of the perceiver. States of
      anxiety have been shown to lead to marked changes in individuals' physiological
      state and their behaviour. To assess the influence of emotional state on
      affordance perception, the perception of action capabilities in near space was
      examined after participants completed an anxiety-provoking task. Anxiety was
      induced immediately prior to tasks that assessed participants' perceived reaching
      ability in Experiment 1, grasping ability in Experiment 2, and the ability to
      pass their hands through apertures in Experiment 3. Results indicated that those
      participants who experienced changes in anxiety underestimated their reaching,
      grasping, and passing ability compared to non-anxious participants. In other
      words, anxious participants were more conservative in their estimations of their
      action capabilities. These results suggest that anxiety influences the perception
      for affordances in near space and are consistent with the notion that anxiety
      induces withdrawal behaviours.

PMID- 22650352
TI  - A strategy to achieve CRT response in permanent atrial fibrillation without
      obligatory atrioventricular node ablation.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is an established method in
      patients with severe heart failure and wide QRS configuration, particularly
      during sinus rhythm (SR). In CRT patients with permanent atrial fibrillation
      (AF), there is no general consensus regarding the need for atrioventricular node
      (AVN) ablation. The aim of this study was to evaluate the benefit of CRT in
      permanent AF with and without AVN ablation. METHODS: New York Heart Association
      classification, QRS duration, and echocardiographic parameters were assessed
      before and after CRT with a follow-up of 12 +/- 3 months. Two hundred thirty
      patients in SR and 46 patients with permanent AF of 2.1 +/- 0.5 years duration
      were studied. AVN ablation was performed only in AF patients with insufficient
      pharmacological rate control evidenced by <=80 % ventricular stimulation.
      RESULTS: Fifteen AF patients underwent AVN ablation. Biventricular pacing
      comparably improved functional status, left ventricular ejection fraction, and
      left ventricular end-diastolic dimensions in all treated groups. Biventricular
      stimulation percentage was 10% lower in pharmacologically treated AF patients
      over 1 year as compared to patients in SR and to AF patients undergoing AVN
      ablation, which did not affect outcome in this patient population. CONCLUSION: In
      patients with permanent AF and CRT, an AVN ablation strategy might not be
      strictly required in all patients.

PMID- 22650353
TI  - Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide
      expansion disease.
AB  - Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of
      C9ORF72 was reported as the cause of chromosome 9p21-linked frontotemporal
      dementia-amyotrophic lateral sclerosis (FTD-ALS). We here report the prevalence
      of the expansion in a hospital-based cohort and associated clinical features
      indicating a wider clinical spectrum of C9ORF72 disease than previously
      described. We studied 280 patients previously screened for mutations in genes
      involved in early onset autosomal dominant inherited dementia disorders. A repeat
      primed polymerase chain reaction amplification assay was used to identify
      pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were
      further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC
      expansion was identified in a total of 14 probands. Three of these presented with
      atypical clinical features and were previously diagnosed with clinical
      olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS)
      and a corticobasal syndrome (CBS). Further, the pathogenic expansion was
      identified in six FTD patients, four patients with FTD-ALS and one ALS patient.
      All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical
      spectrum of C9ORF72 related disease and confirms the hexanucleotide expansion as
      a prevalent cause of FTD-ALS disorders. There was no indication of a modifying
      effect of the ATXN2 gene.

PMID- 22650354
TI  - Conformation-specific display of 4E10 and 2F5 epitopes on self-assembling protein
      nanoparticles as a potential HIV vaccine.
AB  - The self-assembling protein nanoparticle (SAPN) is an antigen-presenting system
      that has been shown to be suitable for use as a vaccine platform. The SAPN
      scaffold is based on the principles of icosahedral symmetry, beginning from a
      monomeric chain that self-assembles into an ordered oligomeric state. The
      monomeric chain contains two covalently linked alpha-helical coiled-coil domains,
      an N-terminal de novo-designed pentameric tryptophan zipper and a C-terminal de
      novo-designed trimeric leucine zipper, which assemble along the internal symmetry
      axes of an icosahedron. In this study, we incorporated the membrane proximal
      external region (MPER) of HIV-1 gp41 from HXB2 into the N-terminal pentamer,
      referred to as MPER-SAPN, attempting to reproduce the alpha-helical state of the
      4E10 epitope while maintaining a structurally less-constrained 2F5 epitope.
      Sprague-Dawley rats were immunized with MPER-SAPNs, and their sera were analyzed
      for induced humoral anti-HIV-1 responses. We show that high membrane proximal
      external region-specific titers can be raised via the repetitive antigen display
      of MPER on the SAPN without the need for adjuvant. However, none of the sera
      displayed a detectable neutralizing activity against HIV-1. Thus, 4E10- and 2F5
      like neutralizing antibodies could not be elicited by MPER conformationally
      restrained in the SAPN context.

PMID- 22650356
TI  - Step-by-step fabrication of a highly oriented crystalline three-dimensional
      pillared-layer-type metal-organic framework thin film confirmed by synchrotron X
      ray diffraction.
AB  - Fabrication of a crystalline ordered thin film based on the porous metal-organic
      frameworks (MOFs) is one of the practical applications of the future functional
      nanomaterials. Here, we report the creation of a highly oriented three
      dimensional (3-D) porous pillared-layer-type MOF thin film on a metal substrate
      using a step-by-step approach based on liquid-phase epitaxy. Synchrotron X-ray
      diffraction (XRD) study clearly indicates that the thin film is crystalline and
      its orientation is highly controlled in both horizontal and vertical directions
      relative to the substrate. This report provides the first confirmation of details
      of not only the crystallinity but also the orientation of 3-D MOF thin film using
      synchrotron XRD. Moreover, we also demonstrate its guest adsorption/desorption
      behavior by using in situ XRD measurements. The results presented here would
      promise useful insights for fabrication of MOF-based nanodevices in the future.

PMID- 22650355
TI  - Aptamer-nanoparticle assembly for logic-based detection.
AB  - In this work, gold nanoparticles perform Boolean logic operations in response to
      two proangiogenic targets important in cancer diagnosis and treatment: PDGF and
      VEGF. In the absence of protein target, gold nanoparticles are initially
      dispersed as a red solution; the addition of target proteins causes nanoparticle
      aggregation, turning the solution blue, as well as the release of dye-labeled
      aptamer probes, which causes an increase in fluorescence. These outputs
      constitute an AND or OR gate for simultaneous protein detection. We believe this
      logic-gate-based detection system will become the basis for novel rapid, cheap,
      and reliable sensors for diagnostic applications. 

PMID- 22650357
TI  - Molecular ecology and adaptation of visual photopigments in craniates.
AB  - In craniates, opsin-based photopigments expressed in the eye encode molecular
      'light sensors' that constitute the initial protein in photoreception and the
      activation of the phototransduction cascade. Since the cloning and sequencing of
      the first vertebrate opsin gene (bovine rod opsin) nearly 30 years ago
      (Ovchinnikov Yu 1982, FEBS Letters, 148, 179-191; Hargrave et al. 1983,
      Biophysics of Structure & Mechanism, 9, 235-244; Nathans & Hogness 1983, Cell,
      34, 807-814), it is now well established that variation in the subtypes and
      spectral properties of the visual pigments that mediate colour and dim-light
      vision is a prevalent mechanism for the molecular adaptation to diverse light
      environments. In this review, we discuss the origins and spectral tuning of
      photopigments that first arose in the agnathans to sample light within the
      ancient aquatic landscape of the Early Cambrian, detailing the molecular changes
      that subsequently occurred in each of the opsin classes independently within the
      main branches of extant jawed gnathostomes. Specifically, we discuss the adaptive
      changes that have occurred in the photoreceptors of craniates as they met the
      ecological challenges to survive in quite differing photic niches, including
      brightly lit aquatic surroundings; the deep sea; the transition to and from land;
      diurnal, crepuscular and nocturnal environments; and light-restricted fossorial
      settings. The review ends with a discussion of the limitations inherent to the
      'nocturnal-bottleneck' hypothesis relevant to the evolution of the mammalian
      visual system and a proposition that transition through a 'mesopic-bottleneck'
      may be a more appropriate model.

PMID- 22650358
TI  - The assessment of the spondyloarthritis international society concept and
      criteria for the classification of axial spondyloarthritis and peripheral
      spondyloarthritis: A critical appraisal for the pediatric rheumatologist.
AB  - This review refers to the origin and current state of the assessment of the
      SpondyloArthritis International Society (ASAS) criteria for the classification of
      axial and peripheral spondyloarthritis (SpA) and the possible implications in the
      pediatric population. The ASAS criteria evolved from the idea that the earlier
      the recognition of patients with ankylosing spondylitis, the better the efficacy
      of tumor necrosis factor blockers. Strategies included the development of new
      concepts, definitions, and techniques for the study of clinical signs and
      symptoms. Of relevance, the new definition of inflammatory back pain (IBP) and
      the introduction of sacroiliitis by magnetic resonance imaging represented the
      most important advance in the early identification of AS in the "pre-radiographic
      stage" of the disease. AS is considered in this paper as a disease continuum with
      symptoms depending on age at onset. The application of those specific strategies
      in children and adolescents with SpA seems limited because the most important
      manifestation in the early stage of disease is not IBP, but peripheral arthritis
      and enthesitis. In this instance, the logical approach to juvenile onset SpA
      according to ASAS criteria should not be through the axial criteria but rather
      the peripheral set of criteria.

PMID- 22650359
TI  - Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by
      upregulation of p21 and p27Kip1.
AB  - BACKGROUND: In our previous study, we detected decreased expression of phospho
      Smad1/5/8 and its upstream signaling molecule, bone morphogenetic protein
      receptor IB subunit (BMPR-IB), in certain glioblastoma tissues, unlike normal
      brain tissues. In order to clarify the functional roles and mechanism of BMPR-IB
      in the development of glioblastoma, we studied the effects of BMPR-IB
      overexpression on glioblastoma cell lines in vitro and in vivo. METHODS: We
      selected glioblastoma cell lines U251, U87, SF763, which have different
      expression of BMPR-IB to be the research subjects. Colony formation analysis and
      FACS were used to detect the effects of BMPR-IB on the growth and proliferation
      of glioblastoma cells in vivo. Immunofluresence was used to detect the
      differentiation changes after BMPR-IB overexpression or knocking-down. Then we
      used subcutaneous and intracranial tumor models to study the effect of BMPR-IB on
      the growth and differentiation of glioblastoma cells in vivo. The genetic
      alterations involved in this process were examined by real-time PCR and western
      blot analysis.ed. RESULTS AND CONCLUSION: Forced BMPR-IB expression in malignant
      human glioma cells, which exhibit lower expression of BMPR-IB, induced the
      phosphorylation and nuclear localization of smad1/5/8 and arrested the cell cycle
      in G1. Additionally, BMPR-IB overexpression could suppress anchorage-independent
      growth and promote differentiation of theses glioblastoma cells. Furthermore,
      overexpression of BMPR-IB inhibited the growth of subcutaneous and intracranial
      tumor xenografts and prolonged the survival of mice injected intracranially with
      BMPR-IB-overexpressing glioblastoma cells. Conversely, inhibition of BMPR-IB
      caused SF763 malignant glioma cells, a line known to exhibit high BMPR-IB
      expression that does not form tumors when used for xenografts, to show increased
      growth and regain tumorigenicity in a nude mouse model system, ultimately
      shortening the survival of these mice. We also observed significant accumulation
      of p21 and p27kip1 proteins in response to BMPR-IB overexpression. Our study
      suggests that overexpression of BMPR-IB may arrest and induce the differentiation
      of glioblastoma cells due to upregulation of p21 and p27kip1 in vitro and that in
      vivo and decreased expression of BMPR-IB in human glioblastoma cells contributes
      to glioma tumorigenicity. BMPR-IB could represent a new potential therapeutic
      target for malignant human gliomas.

PMID- 22650360
TI  - Exposing human epithelial cells to zoledronic acid can mediate osteonecrosis of
      jaw: an in vitro model.
AB  - BACKGROUND: Osteonecrosis of the jaw (ONJ) is a chronic complication of
      bisphosphonate therapy, mainly when intravenous, in cancer patients with bone
      metastases and myeloma. Its pathophysiology is not yet fully elucidated; in
      particular, the molecular/cellular events triggering ONJ remain unclear. This
      complication could result from the effect of bisphosphonates released from bone
      into the soft-tissues, or from osteolysis induced by soft-tissues directly
      exposed to bisphosphonates. This research investigated the possibility that ONJ
      may be evocated by changes induced in osteoblast activity by factors released by
      soft-tissue cells exposed to zoledronic acid. METHODS: An 'in vitro' model was
      used, in which human osteoblast-like MG-63 cells were grown in medium conditioned
      by human keratinocytes NCTC 2544, exposed or not to zoledronic acid (5 or 50
      MUM); 5 MUM zoledronic acid was also directly administered to MG-63 cells.
      RESULTS: In NCTC 2544 cells, zoledronic acid decreased proliferation via
      decreased hydroxy-3-methyl-glutaryl-CoA reductase, suggesting that a decrease in
      healing capability can occur in case of injury. An increased pro-inflammatory
      potential was also observed. Osteoblasts grown in medium conditioned in the
      presence of zoledronic acid showed decreased proliferation and osteogenic
      properties, and increased ability to induce osteoclast differentiation and
      inflammatory process. Zoledronic acid directly administered to MG-63 modulated
      only some parameters and in a lesser extent. CONCLUSIONS: The research evidenced,
      for the first time, the direct involvement of epithelial cells in zoledronic acid
      triggered molecular mechanisms leading to osteonecrosis of the jaw, by modulating
      both osteoblast and osteoclast properties.

PMID- 22650361
TI  - Genome and proteome analysis of 7-7-1, a flagellotropic phage infecting
      Agrobacterium sp H13-3.
AB  - BACKGROUND: The flagellotropic phage 7-7-1 infects motile cells of Agrobacterium
      sp H13-3 by attaching to and traveling along the rotating flagellar filament to
      the secondary receptor at the base, where it injects its DNA into the host cell.
      Here we describe the complete genomic sequence of 69,391 base pairs of this
      unusual bacteriophage. METHODS: The sequence of the 7-7-1 genome was determined
      by pyro(454)sequencing to a coverage of 378-fold. It was annotated using MyRAST
      and a variety of internet resources. The structural proteome was analyzed by SDS
      PAGE coupled electrospray ionization-tandem mass spectrometry (MS/MS). RESULTS:
      Sequence annotation and a structural proteome analysis revealed 127 open reading
      frames, 84 of which are unique. In six cases 7-7-1 proteins showed sequence
      similarity to proteins from the virulent Burkholderia myovirus BcepB1A. Unique
      features of the 7-7-1 genome are the physical separation of the genes encoding
      the small (orf100) and large (orf112) subunits of the DNA packaging complex and
      the apparent lack of a holin-lysin cassette. Proteomic analysis revealed the
      presence of 24 structural proteins, five of which were identified as baseplate
      (orf7), putative tail fibre (orf102), portal (orf113), major capsid (orf115) and
      tail sheath (orf126) proteins. In the latter case, the N-terminus was removed
      during capsid maturation, probably by a putative prohead protease (orf114).

PMID- 22650362
TI  - All-atom structural investigation of kinesin-microtubule complex constrained by
      high-quality cryo-electron-microscopy maps.
AB  - In this study, we have performed a comprehensive structural investigation of
      three major biochemical states of a kinesin complexed with microtubule under the
      constraint of high-quality cryo-electron-microscopy (EM) maps. In addition to the
      ADP and ATP state which were captured by X-ray crystallography, we have also
      modeled the nucleotide-free or APO state for which no crystal structure is
      available. We have combined flexible fitting of EM maps with regular molecular
      dynamics simulations, hydrogen-bond analysis, and free energy calculation. Our
      APO-state models feature a subdomain rotation involving loop L2 and alpha6 helix
      of kinesin, and local structural changes in active site similar to a related
      motor protein, myosin. We have identified a list of hydrogen bonds involving key
      residues in the active site and the binding interface between kinesin and
      microtubule. Some of these hydrogen bonds may play an important role in coupling
      microtubule binding to ATPase activities in kinesin. We have validated our models
      by calculating the binding free energy between kinesin and microtubule, which
      quantitatively accounts for the observation of strong binding in the APO and ATP
      state and weak binding in the ADP state. This study will offer promising targets
      for future mutational and functional studies to investigate the mechanism of
      kinesin motors.

PMID- 22650363
TI  - Porous Teflon ring-solid disk electrode arrangement for differential mass
      spectrometry measurements in the presence of convective flow generated by a jet
      impinging electrode in the wall-jet configuration.
AB  - A porous Teflon ring|solid disk electrode is herein described specifically
      designed for acquiring online mass spectrometric measurements under well-defined
      forced convection created by liquid emerging from a circular nozzle impinging on
      the disk under wall-jet conditions. Measurements were performed for the oxidation
      of hydrazine, N(2)H(4), in a deaerated phosphate buffer electrolyte (pH 7) on Au,
      a process known to yield dinitrogen as the product. The N(2)(+) ion currents,
      measured by the mass spectrometer, i(N(2)(+)), as well as the corresponding
      polarization curves recorded simultaneously displayed very similar s-like shapes
      when plotted as a function of the potential applied to the Au disk. In fact, the
      limiting currents observed both electrochemically and spectrometrically were
      found to be proportional to [N(2)H(4)]. However, the limiting values of
      i(N(2)(+)) did not increase monotonically with the flow rate, nu(f), reaching
      instead a maximum and then decreasing to values independent of nu(f). This
      behavior has been attributed in part to hindrances in the mass transport of gases
      through the porous materials.

PMID- 22650364
TI  - Risk factors influencing the outcome of peptic ulcer bleeding in end stage renal
      diseases after initial endoscopic haemostasis.
AB  - Background and Aims:  Patients suffering from peptic ulcer (PU) bleeding who have
      end-stage renal disease (ESRD) may encounter more adverse outcomes. The primary
      objective is to investigate the risk factors that influence the outcomes of ESRD
      and chronic kidney disease (CKD) patients with PU bleeding after successful
      initial endoscopic haemostasis. Methods:  A total of 540 patients with PU
      bleeding after initial endoscopic haemostasis in a tertiary hospital were
      investigated retrospectively. They were sorted into three groups after randomised
      age-matched adjustment: ESRD group (n = 90), CKD group (n = 90) and control group
      (n = 360). Main outcome measurements were rebleeding, requirement for blood
      transfusion and surgery, length of hospital stay and mortality. Results:  The
      rebleeding rates were 43% for the ESRD group vs. 21% for the CKD group vs. 12%
      for the control group (overall p = < 0.001). Multivariate analysis showed the
      predictors of rebleeding were ESRD, time to endoscope, and non-high-dose proton
      pump inhibitors (PPI) users. The risk factors for bleeding-related mortality were
      presence of moderate degree of CKD and ESRD group, time to endoscope, and Rockall
      score. All-cause mortality was related to presence of moderate degree of CKD and
      ESRD group, platelet count, time to endoscope, Rockall score and length of
      hospital stay. Conclusions:  ESRD patients who suffered from PU bleeding were at
      risk of excessive rebleeding and mortality with frequent occurrence of delayed
      rebleeding. This study suggests that early endoscopy for initial haemostasis and
      high-dose intravenous PPI are associated with the reduction of rebleeding risk
      especially in patients with high Rockall scores.

PMID- 22650366
TI  - Tension trapping of carbonyl ylides facilitated by a change in polymer backbone.
AB  - Epoxidized polybutadiene and epoxidized polynorbornene were subjected to pulsed
      ultrasound in the presence of small molecules capable of being trapped by
      carbonyl ylides. When epoxidized polybutadiene was sonicated, there was no
      observable small molecule addition to the polymer. Concurrently, no appreciable
      isomerization (cis to trans epoxide) was observed, indicating that the epoxide
      rings along the backbone are not mechanically active under the experimental
      conditions employed. In contrast, when epoxidized polynorbornene was subjected to
      the same conditions, both addition of ylide trapping reagents and net
      isomerization of cis to trans epoxide were observed. The results demonstrate the
      mechanical activity of epoxides, show that mechanophore activity is determined
      not only by the functional group but also the polymer backbone in which it is
      embedded, and facilitate a characterization of the reactivity of the ring-opened
      dialkyl epoxide.

PMID- 22650365
TI  - Decoy activity through microRNAs: the therapeutic implications.
AB  - INTRODUCTION: microRNAs (miRNAs), small noncoding RNAs, are deregulated in
      several diseases including cancer. miRNAs regulate gene expression at a
      posttranscriptional level by binding to 5'UTR, coding regions or 3'UTR of
      messenger RNAs (mRNA), inhibiting mRNA translation or causing mRNA degradation.
      The same miRNA can have multiple mRNA targets, and the same mRNA can be regulated
      by various miRNAs. AREAS COVERED: Recently, seminal contributions by several
      groups have implicated miRNAs as components of an RNA-RNA language that involves
      cross-talk between competing endogenous RNAs through a decoy mechanism. We review
      the studies that described miRNAs as players in a biological decoy activity.
      miRNAs can either be trapped by competing endogenous RNAs or interact with
      proteins that have binding sites for mRNAs. EXPERT OPINION: The miRNA decoy
      functions have implications for the design of therapeutic approaches in human
      diseases, including specific ways to overcome resistance to drug therapy and
      future miRNA-based clinical trials design.

PMID- 22650367
TI  - Free glucosylglycerate is a novel marker of nitrogen stress in Mycobacterium
      smegmatis.
AB  - Nitrogen is an essential element for bacterial growth, and as such, bacteria have
      evolved several pathways to assimilate nitrogen and adapt to situations of
      nitrogen limitation. However, the adaptation of mycobacteria to nitrogen stress
      and the regulation of the stress response pathways is unknown. Identification of
      key metabolites produced by mycobacteria during nitrogen stress could therefore
      provide important insights into mycobacterial survival strategies. Here we used
      NMR-based metabolomics to monitor and quantify intracellular and extracellular
      metabolite levels (metabolic footprinting) in Mycobacterium smegmatis grown under
      nitrogen-limiting and nitrogen-rich conditions. There were several metabolic
      differences between the two conditions: following nitrogen run-out, there was an
      increase in intracellular alpha-ketoglutarate and a decrease in intracellular
      glutamine and glutamate levels. In addition, a sugar-derived compound accumulated
      in nitrogen-starved cells that was subsequently assigned as glucosylglycerate
      (GGA). Free GGA production was responsive to nitrogen stress in M. smegmatis but
      not to oxidative or osmotic stress; lack of a functional GGA synthesis pathway
      slightly reduced growth and decreased ammonium uptake rates under nitrogen
      limiting conditions. Hence, GGA could contribute to the fitness of mycobacteria
      under nitrogen limitation.

PMID- 22650368
TI  - The dynamic effects of surfactants on droplet formation in coaxial microfluidic
      devices.
AB  - Droplet emulsification in microfluidic devices involves the constant formation of
      fresh interfaces between two immiscible fluids. When the multiphase system
      contains surfactant, dynamic mass transfer of the surfactant onto the interface
      results in a dynamic interfacial tension different from the static interfacial
      tension measured in an equilibrium state. In this work, we have systematically
      investigated the effects of surfactant concentration and type on the dynamic
      interfacial tension of two different liquid-liquid two phase systems [N
      hexane/water-sodium dodecyl sulfate (SDS) and N-hexane/water
      cetyltrimethylammonium bromide (CTAB)] rapidly producing relatively small
      droplets in coaxial microfluidic devices. Dynamic interfacial tension experiments
      using the pendent drop method and a tensiometer were conducted, and a
      semiempirical equation was developed to put into context the effects of
      surfactants and the experimental conditions on droplet formation and dynamic
      interfacial tension in dynamic microchannel flows. The results presented in this
      work provide a more in-depth understanding of the dynamic effects of surfactants
      on droplet formation and the precise controllable preparation of monodispersed
      droplets in microfluidic devices.

PMID- 22650370
TI  - Fluorescence-detected X-ray magnetic circular dichroism of well-defined Mn(II)
      and Ni(II) doped in MgO crystals: credential evaluation for measurements on
      biological samples.
AB  - L(2,3)-edge X-ray magnetic circular dichroism (XMCD) spectra have been measured
      for the well-defined dilute Ni(II) and Mn(II) ions doped into a MgO crystal, with
      sub-Kelvin dilution refrigerator cooling and 2 T magnetic field magnetization. A
      30-element Ge array X-ray detector has been used to measure the XMCD for these
      dilute ions, whose concentrations are 1400 ppm for Ni(II) and 10,000 ppm for
      Mn(II). Large XMCD effects have been observed for both Ni(II) and Mn(II), and
      multiplet simulation described the observed spectra. The fluorescence-detected L
      edge absorption spectrum and XMCD of Ni(II) in MgO are comparable with both
      theoretical calculations and the total electron yield measured ions in similar
      chemical environments, at least qualitatively validating the use of the sensitive
      fluorescence detection technique for studying XMCD for dilute 3d metal ions, such
      as various metalloproteins. Sum rule analyses on the XMCD spectra are also
      performed. In addition, these XMCD measurements have also been used to obtain the
      sample's magnetization curve and the beamline's X-ray helicity curve. This study
      also illustrated that bend magnet beamlines are still useful in examining XMCD on
      dilute and paramagnetic metal sites.

PMID- 22650369
TI  - Prospective hospital-based case-control study to assess the effectiveness of
      pandemic influenza A(H1N1)pdm09 vaccination and risk factors for hospitalization
      in 2009-2010 using matched hospital and test-negative controls.
AB  - BACKGROUND: We performed a case-control study to estimate vaccine effectiveness
      (VE) for prevention of hospitalization due to pandemic influenza A(H1N1)pdm09
      (pH1N1) and to identify risk factors for pH1N1 and acute respiratory infection
      (ARI) in 10 hospitals in Berlin from December 2009 to April 2010. METHODS: Cases
      were patients aged 18-65 years with onset of ARI <=10 days before admission
      testing positive for pH1N1 by PCR performed on nasal and throat swabs or by
      serological testing. Cases were compared to (1) matched hospital controls with
      acute surgical, traumatological or other diagnoses matched on age, sex and
      vaccination probability, and (2) ARI patients testing negative for pH1N1.
      Additionally, ARI cases were compared to matched hospital controls. A
      standardized interview and chart review elicited demographic and clinical data as
      well as potential risk factors for pH1N1/ARI. VE was estimated by 1-(Odds ratio)
      for pH1N1-vaccination >=10 days before symptom onset using exact logistic
      regression analysis. RESULTS: Of 177 ARI cases recruited, 27 tested pH1N1
      positive. A monovalent AS03-adjuvanted pH1N1 vaccine was the only pandemic
      vaccine type identified among cases and controls (vaccination coverage in control
      group 1 and 2: 15% and 5.9%). The only breakthrough infections were observed in 2
      of 3 vaccinated HIV positive pH1N1 patients. After exclusion of HIV positive
      participants, VE was 96% (95%CI: 26-100%) in the matched multivariate analysis
      and 46% (95%CI: -376-100%) in the test-negative analysis. Exposure to children in
      the household was independently associated with hospitalization for pH1N1 and
      ARI. CONCLUSIONS: Though limited by low vaccination coverage and number of pH1N1
      cases, our results suggest a protective effect of the AS03-adjuvanted pH1N1
      vaccine for the prevention of pH1N1 hospitalization. The use of hospital but not
      test-negative controls showed a statistically protective effect of pH1N1
      vaccination and permitted the integrated assessment of risk factors for pH1N1
      infection. To increase statistical power and to permit stratified analyses (e.g.
      VE for specific risk groups), the authors suggest pooling of future studies
      assessing effectiveness of influenza vaccines for prevention of severe disease
      from different centres.

PMID- 22650372
TI  - Medicinal chemistry of tumor necrosis factor-alpha inhibitors and related
      oxidative stress.

PMID- 22650373
TI  - From the deepest sea shelf to the uppermost kitchen cabinet shelf: the quest for
      novel TNF-alpha inhibitors.
AB  - TNF-alpha was discovered more then 20 years ago as a cytokine implicated in a
      wide range of cell signaling pathways, many of which are known to lead to the
      activation of genes involved in inflammation and carcinogenesis. TNF-alpha is
      involved in the pathogenesis of many diseases, including Crohn's disease,
      diabetes, septic shock, tumorigenesis, rheumatoid arthritis, psoriatic arthritis
      and inflammatory bowel disease. Multidisciplinary research endeavoring to
      understand the biomolecular and biomedicinal properties of TNF-alpha has never
      faded away, and the search for natural products able to inhibit TNF-alpha
      remains, to date, a hot topic of investigation. Over the last 10 years, many TNF
      alpha-inhibiting natural compounds have been discovered, and their anti-TNF-alpha
      activities have been described. The present review describes the major cell
      signaling pathways activated by TNF-alpha and discusses the chemical and
      biological properties of TNF-alpha-inhibiting natural products, focusing on
      compounds that are able to inhibit TNF-alpha-related signal transduction pathways
      or TNF-alpha gene expression.

PMID- 22650374
TI  - TNF-alpha inhibitors with anti-oxidative stress activity from natural products.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a major cytokine involved in the
      inflammatory response. Elevated TNF-alpha expression has been found to be
      associated with the development of diabetes, septic shock, tumorigenesis,
      cardiovascular diseases, rheumatoid arthritis and inflammatory bowel disease. In
      the past decade, the success of anti-TNF-alpha biologics has valuated the
      importance of the blockade of TNF-alpha production in the treatment of patients
      with various inflammatory diseases. Oxidative stress is another important element
      in oxidative/inflammatory responses that directly linked to oxidation of
      proteins, DNA and lipids. The increased oxidant levels could activate nuclear
      factor-kappaB (NFkappa-B), signal transduction and gene expression of TNF-alpha,
      interleukin-1 (IL-1) and other pro-inflammatory cytokines. Therefore, TNF-alpha
      inhibitors with anti-oxidative stress activity may have multiple target effect
      that could exhibit excellent anti-inflammatory activities. The review briefly
      highlights the pathological roles of TNF-alpha and oxidative stress in
      inflammation, and covers those natural products as TNF-alpha inhibitors capable
      of anti-oxidative stress activity.

PMID- 22650375
TI  - Therapeutic potential of natural products from terrestrial plants as TNF-alpha
      antagonist.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine produced by
      monocytes, macrophages, neutrophils, T-cells, mast cells, epithelial cells,
      osteoblasts and dendritic cells. It can regulate numerous cellular and biological
      processes such as immune function, cell differentiation, proliferation, apoptosis
      and energy metabolism. It is also involved in the pathogenesis of multiple
      chronic inflammatory or autoimmune diseases. The biological activities of TNF
      alpha mediated by two receptors TNFR1 and TNFR2. Its activity can be inhibited by
      neutralizing monoclonal antibodies or soluble TNF receptors. The inhibition of
      its biological activities using anti TNF-alpha antibodies represents an approved
      strategy for the treatment of various diseases like cancer, autoimmune diseases,
      inflammations etc. The involvement of TNF-alpha cytokine in the various types of
      diseases provide the therapeutic rationale for the development of TNF-alpha
      antagonist. A large number of natural and synthetic compounds are currently being
      investigated for TNF-alpha inhibitory activity. Since the synthetic molecules are
      always associated with their side effects hence it is beneficial to develop the
      natural strategies as the alternative sources. There are many medicinal plants
      which are traditionally used for the treatment of the diseases associated with
      TNF-alpha inhibition. Hence, in this review article we make an approach to
      provide a platform for the development of TNF-alpha antagonist from natural
      resources.

PMID- 22650376
TI  - Thalidomide: chemistry, therapeutic potential and oxidative stress induced
      teratogenicity.
AB  - Thalidomide and its one analogue, lenalidomide (CC5103 or revlimid) are recently
      approved for the treatment of multiple myeloma. Multiple myeloma is characterized
      by an overproduction of malignant plasma cells in the bone marrow. The journey of
      thalidomide was started in 1956 when it was marketed as a non-barbiturate
      sedative agent. It was considered as a "wonder drug" that provided safe and sound
      sleep and hence, used to cure morning sickness in pregnant women. Later, in 1961,
      it was withdrawn from the world market due to its serious side effects, i.e.,
      teratogenic activity. However, the recent decade has witnessed a true renaissance
      in interest in its broad biological activity. In particular, thalidomide was
      reevaluated and attracted significant attention due to its selective inhibitory
      activity of tumor necrosis factor-alpha (TNF-alpha), which is a clinically
      important activity against serious diseases such as rheumatoid arthritis, Crohn's
      disease, leprosy, AIDS, and various cancers. The comeback of thalidomide to the
      legitimate status of a marketed drug came in 1998 when it received FDA approval
      for the treatment of erythema nodosum leprosum (ENL). Recently, the drug has got
      FDA approval for the treatment of multiple myeloma. In the last few years, number
      of thalidomide analogues have been synthesized and are in clinical development as
      a class of immunomodulatory drugs. Among these, lenalidomide is more potent than
      thalidomide, and is also non-neurotoxic. It was shown in vitro studies to induce
      apoptosis or arrest growth even in resistant multiple myeloma cell lines,
      decrease binding of the cells to bone marrow stromal cells, and stimulate host
      natural killer cell immunity. It also inhibits tumour growth and decreases
      angiogenesis. Earlier reviews have described the pharmacological aspects of
      thalidomide and a review has focused only on synthetic aspect of thalidomide.
      However, review focusing on chemistry and metabolism and mechanism of biological
      activity is still lacking. In this review, we will concisely describe the
      therapeutic aspects, metabolism and synthesis of thalidomide.

PMID- 22650377
TI  - TNF alpha signaling beholds thalidomide saga: a review of mechanistic role of TNF
      alpha signaling under thalidomide.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic inflammatory cytokine.
      The cytokine possesses both growth stimulating properties and growth inhibitory
      processes, and it appears to have self regulatory properties as well. Agents like
      etanercept and infliximab showed beneficial effects against rheumatoid arthritis
      by modulationg TNF-alpha proteins, however, these agents are largely unable to
      penetrate the blood-brain barrier, which severely limits their use in different
      conditions. Thalidomide, an inhibitor of TNF-alpha protein synthesis is readily
      capable of crossing the blood-brain barrier and thus thalidomide and its analogs
      are excellent candidates for use in determining the potential value of anti-TNF
      alpha therapies in a variety of diseases. Thalidomide blocks TNF-alpha expression
      by different possible mechanisms. Down regulation of nuclear factor kappa-light
      chain-enhancer of activated B cells (NF-kB), an essential transcription factor
      for TNF and other cytokines under thalidomide treatment leads to reduction in the
      TNF-alpha expression. Additionally, myeloid differentiation factor 88 (MyD88), an
      adapter protein regulates the expression of TNF under thalidomide treatment.
      Thalidomide treatment also leads to destruction of TNF-alpha mRNA thus, reducing
      the total expression of TNF-alpha protein. Thalidomide also targets reactive
      oxygen species (ROS) and alpha(1)-acid glycoprotein (AGP) to regulate TNF-alpha.
      In the present review, we discuss different possible mechanism that regulates TNF
      alpha under thalidomide treatment. Additionally, we suggest novel strategies for
      the future targeting combination therapies of thalidomide and its analogs with
      different other anti-inflammatory drug to curb TNF-alpha associated diseases.

PMID- 22650378
TI  - Depression reduces perceptual sensitivity for positive words and pictures.
AB  - There is evidence of maladaptive attentional biases for lexical information
      (e.g., Atchley, Ilardi, & Enloe, 2003; Atchley, Stringer, Mathias, Ilardi, &
      Minatrea, 2007) and for pictographic stimuli (e.g., Gotlib, Krasnoperova, Yue, &
      Joormann, 2004) among patients with depression. The current research looks for
      depressotypic processing biases among depressed out-patients and non-clinical
      controls, using both verbal and pictorial stimuli. A d' measure (sensitivity
      index) was used to examine each participant's perceptual sensitivity threshold.
      Never-depressed controls evidenced a detection bias for positive picture stimuli,
      while depressed participants had no such bias. With verbal stimuli, depressed
      individuals showed specific decrements in the detection of positive person
      referent words (WINNER), but not with positive non-person-referent words
      (SUNSHINE) or with negative words. Never-depressed participants showed no such
      differences across word types. In the current study, depression is characterised
      both by an absence of the normal positivistic biases seen in individuals without
      mood disorders (consistent with McCabe & Gotlib, 1995), and by a specific
      reduction in sensitivity for person-referent positive information that might be
      inconsistent with depressotypic self-schemas.

PMID- 22650379
TI  - Cross-sectional and longitudinal abnormalities in brain structure in children
      with severe mood dysregulation or bipolar disorder.
AB  - BACKGROUND: There is debate as to whether chronic irritability (operationalized
      as severe mood dysregulation, SMD) is a developmental form of bipolar disorder
      (BD). Although structural brain abnormalities in BD have been demonstrated, no
      study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either
      cross-sectionally or over time. Furthermore, the developmental trajectories of
      structural abnormalities in BD or SMD are unknown. This study provides such data
      in BD, SMD, and HV. METHODS: An optimized, modulated voxel-based morphometry
      (VBM) analysis was conducted on structural MRI scans from 201 children (78 SMD,
      55 BD, and 68 HV). In addition, 92 children (31 SMD, 34 BD, and 27 HV) were
      rescanned after 2 years (mean interval 1.99 +/- 0.94 years), to compare time
      related changes among the three groups. RESULTS: Cross-sectionally, the groups
      differed in gray matter (GM) volume in presupplementary motor area (pre-SMA),
      dorsolateral prefrontal cortex (DLPFC), insula, and globus pallidus. The cortical
      differences were driven mainly by increased GM volume in HV compared with BD and
      SMD. In globus pallidus, there was increased GM in BD compared with HV and SMD.
      Longitudinally, group-by-time interactions were evident in two clusters in the
      superior/inferior parietal lobule (R SPL/IPL) and in the precuneus. In both
      clusters, the interactions were driven by an abnormal increase in volume in BD.
      CONCLUSIONS: Cross-sectionally, both BD and SMD are associated with structural
      abnormalities in frontal cortex, insula, and basal ganglia. Although some of
      these deficits overlap (insula and DLPFC), others differentiate SMD and BD (pre
      SMA and globus pallidus). Abnormal developmental trajectories in lateral parietal
      cortex and precuneus are present in, and unique to, BD. Because of the high
      proportion of co-occurring ADHD in the SMD subjects, we could not separate
      effects of ADHD from those of SMD, and future research including a nonirritable
      ADHD group must address this issue.

PMID- 22650380
TI  - A content analysis of chronic diseases social groups on Facebook and Twitter.
AB  - Research on the use of social networks for health-related purposes is limited.
      This study aims to characterize the purpose and use of Facebook and Twitter
      groups concerning colorectal cancer, breast cancer, and diabetes. We searched in
      Facebook ( www.facebook.com ) and Twitter ( www.twitter.com ) using the terms
      "colorectal cancer," "breast cancer," and "diabetes." Each important group has
      been analyzed by extracting its network name, number of members, interests, and
      Web site URL. We found 216 breast cancer groups, 171 colorectal cancer groups,
      and 527 diabetes groups on Facebook and Twitter. The largest percentage of the
      colorectal cancer groups (25.58%) addresses prevention, similarly to breast
      cancer, whereas diabetes groups are mainly focused on research issues (25.09%).
      There are more social groups about breast cancer and diabetes on Facebook (around
      82%) than on Twitter (around 18%). Regarding colorectal cancer, the difference is
      less: Facebook had 62.23%, and Twitter 31.76%. Social networks are a useful tool
      for supporting patients suffering from these three diseases. Regarding the use of
      these social networks for disease support purposes, Facebook shows a higher usage
      rate than Twitter, perhaps because Twitter is newer than Facebook, and its use is
      not so generalized.

PMID- 22650381
TI  - Management of cluster headache.
AB  - The prevalence of cluster headache is 0.1% and cluster headache is often not
      diagnosed or misdiagnosed as migraine or sinusitis. In cluster headache there is
      often a considerable diagnostic delay - an average of 7 years in a population
      based survey. Cluster headache is characterized by very severe or severe orbital
      or periorbital pain with a duration of 15-180 minutes. The cluster headache
      attacks are accompanied by characteristic associated unilateral symptoms such as
      tearing, nasal congestion and/or rhinorrhoea, eyelid oedema, miosis and/or
      ptosis. In addition, there is a sense of restlessness and agitation. Patients may
      have up to eight attacks per day. Episodic cluster headache (ECH) occurs in
      clusters of weeks to months duration, whereas chronic cluster headache (CCH)
      attacks occur for more than 1 year without remissions. Management of cluster
      headache is divided into acute attack treatment and prophylactic treatment. In
      ECH and CCH the attacks can be treated with oxygen (12 L/min) or subcutaneous
      sumatriptan 6 mg. For both oxygen and sumatriptan there are two randomized,
      placebo-controlled trials demonstrating efficacy. In both ECH and CCH, verapamil
      is the prophylactic drug of choice. Verapamil 360 mg/day was found to be superior
      to placebo in one clinical trial. In clinical practice, daily doses of 480-720 mg
      are mostly used. Thus, the dose of verapamil used in cluster headache treatment
      may be double the dose used in cardiology, and with the higher doses the PR
      interval should be checked with an ECG. At the start of a cluster, transitional
      preventive treatment such as corticosteroids or greater occipital nerve blockade
      can be given. In CCH and in long-standing clusters of ECH, lithium, methysergide,
      topiramate, valproic acid and ergotamine tartrate can be used as add-on
      prophylactic treatment. In drug-resistant CCH, neuromodulation with either
      occipital nerve stimulation or deep brain stimulation of the hypothalamus is an
      alternative treatment strategy. For most cluster headache patients there are
      fairly good treatment options both for acute attacks and for prophylaxis. The big
      problem is the diagnosis of cluster headache as demonstrated by the diagnostic
      delay of 7 years. However, the relatively short-lasting attack of pain in one eye
      with typical associated symptoms should lead the family doctor to suspect cluster
      headache resulting in a referral to a neurologist or a headache centre with
      experience in the treatment of cluster headache.

PMID- 22650382
TI  - Facial and vocal affect perception in people at ultra-high risk of psychosis,
      first-episode schizophrenia and healthy controls.
AB  - AIM: The study aims to investigate affect recognition in young people at
      different stages of psychotic illness. METHODS: Seventy-nine ultra-high risk
      patients, 30 first-episode schizophrenia patients and 30 healthy control subjects
      completed a facial affect labelling test and an affective prosody recognition
      test. Psychiatric symptoms were assessed using the Positive and Negative Syndrome
      Scale (PANSS). RESULTS: We observed significant impairments in facial and vocal
      emotion recognition in both of the clinical groups compared with the control
      group. These group differences remained significant when age, sex and education
      were taken into account. CONCLUSIONS: The findings suggest that emotion
      recognition impairments may be independent of the stage of illness in
      schizophrenia. Deficits in emotion recognition may be present before the full
      expression of psychotic illness, and may contribute to the social cognition and
      social functioning deficits apparent in emerging psychotic disorders.

PMID- 22650383
TI  - Mate choice and the genetic basis for colour variation in a polymorphic dart
      frog: inferences from a wild pedigree.
AB  - Understanding how reproductive barriers evolve during speciation remains an
      important question in evolution. Divergence in mating preferences may be a common
      first step in this process. The striking colour pattern diversity of strawberry
      dart frog (Dendrobates pumilio) populations has likely been shaped by sexual
      selection. Previous laboratory studies have shown that females attend to male
      coloration and prefer to court with males of their own colour, suggesting that
      divergent morphs may be reproductively isolated. To test this hypothesis, we used
      molecular data to estimate pedigree relationships from a polymorphic population.
      Whereas in the laboratory both red and yellow females preferred to court with
      males of their own phenotype, our pedigree shows a pattern of assortative mating
      only for red females. In the wild, yellow females appear to be less choosy about
      their mates, perhaps because they incur higher costs associated with searching
      than females of the more common red phenotype. We also used our pedigree to
      investigate the genetic basis for colour-pattern variation. The phenotype
      frequencies we observed were consistent with those expected if dorsal background
      coloration is controlled by a single locus, with complete dominance of red over
      yellow. Our results not only help clarify the role of sexual selection in
      reducing gene flow, but also shed light on the mechanisms underlying colour
      pattern variation among sympatric colour morphs. The difference we observed
      between mating preferences measured under laboratory conditions and the pattern
      of mate choice observed in the wild highlight the importance of field studies for
      understanding behavioural reproductive isolation.

PMID- 22650384
TI  - Glass-encapsulated light harvesters: more efficient dye-sensitized solar cells by
      deposition of self-aligned, conformal, and self-limited silica layers.
AB  - A major loss mechanism in dye-sensitized solar cells (DSCs) is recombination at
      the TiO(2)/electrolyte interface. Here we report a method to reduce greatly this
      loss mechanism. We deposit insulating and transparent silica (SiO(2)) onto the
      open areas of a nanoparticulate TiO(2) surface while avoiding any deposition of
      SiO(2) over or under the organic dye molecules. The SiO(2) coating covers the
      highly convoluted surface of the TiO(2) conformally and with a uniform thickness
      throughout the thousands of layers of nanoparticles. DSCs incorporating these
      selective and self-aligned SiO(2) layers achieved a 36% increase in relative
      efficiency versus control uncoated cells.

PMID- 22650412
TI  - The E288K colon tumor variant of DNA polymerase beta is a sequence specific
      mutator.
AB  - DNA polymerase beta (pol beta) is the main polymerase involved in base excision
      repair (BER), which is a pathway responsible for the repair of tens of thousands
      of DNA lesions per cell per day. Our recent efforts in sequencing colon tumors
      showed that 40% of the tumors sequenced possessed a variant in the coding region
      of the POLB gene; one of these variants is E288K. Expression of the E288K variant
      in cells leads to an increase in the frequency of mutations at AT base pairs. In
      vitro, the E288K variant is as active as and binds one-base-gapped DNA with the
      same affinity as wild-type pol beta. Single-turnover kinetic data for the E288K
      variant show that its mutator phenotype is specific for misincorporating opposite
      template A up to 6-fold more than the wild-type enzyme and that this is due to a
      decrease in the degree of discrimination in nucleotide binding. Molecular
      modeling suggests that the substitution of Lys at position 288 causes the
      polymerase to adopt a more open conformation, which may be disrupting the
      nucleotide binding pocket. This may explain the reduced degree of discrimination
      at the level of nucleotide binding. The enhanced mutagenesis of the E288K variant
      could lead to genomic instability and ultimately a malignant tumor phenotype.

PMID- 22650413
TI  - Loss of adhesion/growth-regulatory galectin-9 from squamous cell epithelium in
      head and neck carcinomas.
AB  - Galectins are potent effectors of cell adhesion and growth regulation. Their
      expression as comples network necessitates systematic study of each member of
      this family. Toward this aim, we here focus on the tandem-repeat-type galectin-9.
      Its presence is monitored in normal squamous epithelium of the head and neck, the
      surgical margin, and four types of squamous cell carcinoma. Lectin presence was
      detected in cells of the basal layer of the epithelium. All galectin-9-negative
      epithelia showed aberrant positivity for keratins 14 and 19. The surgical margin
      presented either a normal pattern of galectin-9 and keratin presence or a mosaic
      like presence/absence of galectin-9 and aberrant expression of both keratins 14
      and 19. All studied specimens of squamous cell carcinoma were negative for
      galectin-9. When biotinylated galectin-9, or its N-terminal domain, was tested,
      no significant tissue reactivity for both probes was observed. Neuraminidase
      treatment generated reactivity to the N-domain. In conclusion, galectin-9 is
      expressed in the majority of samples of normal epithelium, along with regular
      presence of keratins 14 or 19. This lectin can represent a potential marker of
      normality in the cases of the studied squamous cell epithelia.

PMID- 22650414
TI  - Increased conductance of individual self-assembled GeSi quantum dots by inter-dot
      coupling studied by conductive atomic force microscopy.
AB  - The conductive properties of individual self-assembled GeSi quantum dots (QDs)
      are investigated by conductive atomic force microscopy on single-layer (SL) and
      bi-layer (BL) GeSi QDs with different dot densities at room temperature. By
      comparing their average currents, it is found that the BL and high-density QDs
      are more conductive than the SL and low-density QDs with similar sizes,
      respectively, indicating the existence of both vertical and lateral couplings
      between GeSi QDs at room temperature. On the other hand, the average current of
      the BL QDs increases much faster with the bias voltage than that of the SL QDs
      does. Our results suggest that the QDs' conductive properties can be greatly
      regulated by the coupling effects and bias voltages, which are valuable for
      potential applications.

PMID- 22650415
TI  - The phenotype of a CASQ2 mutation in a Saudi family with catecholaminergic
      polymorphic ventricular tachycardia.
AB  - Catecholaminergic polymorphic ventricular tachycardia (CPVT) manifests with
      episodic syncope or sudden death in young patients following physical activity or
      emotional stress. The autosomal recessive form of CPVT is caused by mutations in
      the CASQ2 gene. In a consanguineous family, a novel homozygous CASQ2 mutation
      (p.L77P) was identified in a child with CPVT who required implantation of a
      cardioverter defibrillator due to episodes of syncope while on medical therapy.
      Genetic testing found the younger sibling, who had normal initial clinical
      screening, to be affected. Our cases underscore the importance of family
      screening through genetic testing to preemptively apply the appropriate medical
      intervention in CPVT.

PMID- 22650418
TI  - Building an R&D chemical registration system.
AB  - Small molecule chemistry is of central importance to a number of R&D companies
      in diverse areas such as the pharmaceutical, nutraceutical, food flavoring, and
      cosmeceutical industries. In order to store and manage thousands of chemical
      compounds in such an environment, we have built a state-of-the-art master
      chemical database with unique structure identifiers. Here, we present the concept
      and methodology we used to build the system that we call the Unique Compound
      Database (UCD). In the UCD, each molecule is registered only once (uniqueness),
      structures with alternative representations are entered in a uniform way
      (normalization), and the chemical structure drawings are recognizable to chemists
      and to a cartridge. In brief, structural molecules are entered as neutral
      entities which can be associated with a salt. The salts are listed in a
      dictionary and bound to the molecule with the appropriate stoichiometric
      coefficient in an entity called "substance". The substances are associated with
      batches. Once a molecule is registered, some properties (e.g., ADMET prediction,
      IUPAC name, chemical properties) are calculated automatically. The UCD has both
      automated and manual data controls. Moreover, the UCD concept enables the
      management of user errors in the structure entry by reassigning or archiving the
      batches. It also allows updating of the records to include newly discovered
      properties of individual structures. As our research spans a wide variety of
      scientific fields, the database enables registration of mixtures of compounds,
      enantiomers, tautomers, and compounds with unknown stereochemistries.

PMID- 22650416
TI  - Bacterial urinary tract infection after solid organ transplantation in the
      RESITRA cohort.
AB  - BACKGROUND: Urinary tract infection (UTI) is the most common infection in renal
      transplant patients, but it is necessary to determine the risk factors for
      bacterial UTI in recipients of other solid organ transplants (SOTs), as well as
      changes in etiology, clinical presentation, and prognosis. METHODS: In total,
      4388 SOT recipients were monitored in 16 transplant centers belonging to the
      Spanish Network for Research on Infection in Transplantation (RESITRA). The
      frequency and characteristics of bacterial UTI in transplant patients were
      obtained prospectively from the cohort (September 2003 to February 2005).
      RESULTS: A total of 192 patients (4.4%) presented 249 episodes of bacterial UTI
      (0.23 episodes per 1000 transplantation days); 156 patients were kidney or kidney
      pancreas transplant recipients, and 36 patients were liver, heart, and lung
      transplant recipients. The highest frequency was observed in renal transplants
      (7.3%). High frequency of cystitis versus pyelonephritis without related
      mortality was observed in both groups. The most frequent etiology was Escherichia
      coli (57.8%), with 25.7% producing extended-spectrum beta-lactamase (ESBL). In
      all transplants but renal, most cases occurred in the first month after
      transplantation. Cases were uniformly distributed during the first 6 months after
      transplantation in renal recipients. Age (odds ratio [OR] per decade 1.1, 95%
      confidence interval [CI] 1.02-1.17), female gender (OR 1.74, 95% CI 1.42-2.13),
      and the need for immediate post-transplant dialysis (OR 1.63, 95% CI 1.29-2.05)
      were independent variables associated with bacterial UTI in renal and kidney
      pancreas recipients. The independent risk factors identified in non-renal
      transplants were age (OR per decade 1.79, 95% CI 1.09-3.48), female gender (OR
      1.7, 95% CI 1.43-2.49), and diabetes (OR 1.02, 95% CI 1.001-1.040). CONCLUSIONS:
      UTI was frequent in renal transplants, but also not unusual in non-renal
      transplants. Because E. coli continues to be the most frequent etiology, the
      emergence of ESBL-producing strains has been identified as a new problem. In both
      populations, most cases were cystitis without related mortality. Although the
      first month after transplantation was a risk period in all transplants, cases
      were uniformly distributed during the first 6 months in renal transplants. Age
      and female gender were identified as risk factors for UTI in both populations.
      Other particular risk factors were the need for immediate post-transplant
      dialysis in renal transplants and diabetes in non-renal transplants.

PMID- 22650417
TI  - Shape matters: intravital microscopy reveals surprising geometrical dependence
      for nanoparticles in tumor models of extravasation.
AB  - Delivery is one of the most critical obstacles confronting nanoparticle use in
      cancer diagnosis and therapy. For most oncological applications, nanoparticles
      must extravasate in order to reach tumor cells and perform their designated task.
      However, little understanding exists regarding the effect of nanoparticle shape
      on extravasation. Herein we use real-time intravital microscopic imaging to
      meticulously examine how two different nanoparticles behave across three
      different murine tumor models. The study quantitatively demonstrates that high
      aspect ratio single-walled carbon nanotubes (SWNTs) display extravasational
      behavior surprisingly different from, and counterintuitive to, spherical
      nanoparticles although the nanoparticles have similar surface coatings, area, and
      charge. This work quantitatively indicates that nanoscale extravasational
      competence is highly dependent on nanoparticle geometry and is heterogeneous.

PMID- 22650419
TI  - Polyelectrolyte gels comprising a lipophilic, cost-effective aluminate as
      fluorine-free absorbents for chlorinated hydrocarbons and diesel fuel.
AB  - Superabsorbent polymers comprising a lipophilic, halogen-free, and cost-effective
      aluminate ("altebate") anion have been synthesized. The polyelectrolytes are
      based on octadecyl acrylate monomers, 0.8-1 mol % ethylene dimethacrylate cross
      linker, and 5 mol % N-3-acroyloxypropyl trialkylammonium altebate. At 30  degrees
      C, swelling degrees of 70 (chlorobenzene), 102 (CHCl3), 130 (THF), 163
      (ClCH2CH2Cl), 171 (dichlorobenzene), and 208 (CH2Cl2) have been determined. The
      polyelectrolyte absorbs reversibly diesel fuel with a swelling degree of 34, even
      in the presence of water. Swelling times and critical swelling temperatures have
      also been determined. The challenges for the development of oil absorbents are
      discussed. 

PMID- 22650420
TI  - Versatile supramolecular gelators that can harden water, organic solvents and
      ionic liquids.
AB  - We developed novel supramolecular gelators with simple molecular structures that
      could harden a broad range of solvents: aqueous solutions of a wide pH range,
      organic solvents, edible oil, biodiesel, and ionic liquids at gelation
      concentrations of 0.1-2 wt %. The supramolecular gelators were composed of a long
      hydrophobic tail, amino acids and gluconic acid, which were prepared by liquid
      phase synthesis. Among seven types of the gelators synthesized, the gelators
      containing L-Val, L-Leu, and L-Ile exhibited high gelation ability to various
      solvents. These gelators were soluble in aqueous and organic solvents, and also
      in ionic liquids at high temperature. The gelation of these solvents was
      thermally reversible. The microscopic observations (TEM, SEM, and CLSM) and small
      angle X-ray scattering (SAXS) measurements suggested that the gelator molecules
      self-assembled to form entangled nanofibers in a large variety of solvents,
      resulting in the gelation of these solvents. Molecular mechanics and density
      functional theory (DFT) calculations indicated the possible molecular packing of
      the gelator in the nanofibers. Interestingly, the gelation of an ionic liquid by
      our gelator did not affect the ionic conductivity of the ionic liquid, which
      would provide an advantage to electrochemical applications.

PMID- 22650421
TI  - Bispecific antibody-mediated detection of the Staphylococcus aureus
      thermonuclease.
AB  - We report a novel fluorescence-based immunoassay which enables qualitative
      detection of the Staphylococcus aureus Thermonuclease (TNase) enzyme, thus
      providing confirmation of the presence of the S. aureus bacterium in vitro. The
      biomedical problem of chronic wound healing and the continuing emergence of
      antibiotic-resistant species is addressed in the development of a detection
      system capable of the rapid, real-time assessment of bacterial load and
      diversity. The use of bispecific antibodies (BsAb) provides integration of the
      molecular detection and signal response components of a standard immunoassay due
      to steric hindrance-mediated release of prebound fluorescent reporter molecules
      upon specific binding of TNase to adjacent sites. Rhodamine and fluorescein
      labeled hemocyanin from Megathura crenulata (KLH) were prepared as effective
      immunoconjugates containing a sensitive fluorescent reporter moiety. BsAb that
      both specifically quenched the fluorescence of the reporter conjugate and bound
      the TNase target antigen were produced using cell fusion techniques. Assays were
      then performed to analyze the properties attributable to the steric hindrance
      mediated release of the fluorescent reporter molecules upon adjacent TNase
      binding. This was performed by monitoring the intensity of fluorescence emission
      of the immunogenic reporter conjugate released into an aqueous environment at 578
      and 520 nm, respectively.

PMID- 22650422
TI  - Therapeutic strategies for the prevention and treatment of cytomegalovirus
      infection.
AB  - INTRODUCTION: CMV remains a significant cause of morbidity and mortality in
      immunosuppressed patients, particularly following allogeneic haematopoietic
      transplantation. This reflects the inability of depressed host immunity to
      contain viral replication, principally through the loss of T-cell function. There
      is a clear rationale for the restoration of CMV-specific immunity using adoptive
      T-cell immunotherapy. AREAS COVERED: This review analyses current treatment
      strategies for prophylaxis and preemptive treatment of CMV with a particular
      focus on patients following allogeneic haematopoietic transplantation. The main
      emphasis of this review is the role of adoptive T-cell therapy, particularly some
      of the newer direct selection technologies that allow the rapid generation of a
      GMP-compliant cellular product. Relevant studies were selected from PubMed.
      Search terms: allogeneic transplant, cytomegalovirus, multidrug-resistant virus,
      adoptive T-cell therapy. EXPERT OPINION: A number of early studies showed that T
      cell therapies can be delivered safely and are efficacious. However, they relied
      on culture techniques that make wider application difficult. Newer direct
      selection techniques have allowed production of cellular products more rapidly,
      cheaply, and to GMP standards. Clinical trials will help define the role of these
      cellular products, which have the potential to alter our entire approach to the
      treatment of CMV infection.

PMID- 22650423
TI  - Identification of a transparent mutant tiger barb Puntius tetrazona and its use
      for in vivo observation of a Pleistophora sp. (Microsporidia) infection.
AB  - A transparent mutant tiger barb Puntius tetrazona was identified and
      characterized by its transparent body, which allows clear visualization of
      internal organs. Hybridization of this mutant with the albino variant produces a
      transparent and albinoid double phenotype, and the transparency of this mutant is
      controlled by a recessive allele. Light microscopic and ultrastructural
      examinations show that in contrast to normal individuals, transparent mutants
      lack iridophores, and light penetrates unimpeded through the body. Pleistophora
      sp. infection was observed in vivo, allowing live observation of parasite
      dissemination and the consequent pathological alterations in the fish body as
      well as the simultaneous acquisition of data on the dynamics and spatial pattern
      of pathogenic invasion. It is superior to common fish models, as dynamic
      experimental data can be obtained from individual fish.

PMID- 22650424
TI  - Reproductive biology of the spotback skate Atlantoraja castelnaui in the south
      west Atlantic Ocean.
AB  - This study provides information on the reproduction of spotback skate Atlantoraja
      castelnaui. A total of 232 individuals (119 females and 113 males) were obtained
      from surveys carried out between 2003 and 2006, from the south-west Atlantic
      Ocean, between 34 and 42 degrees  S and <50 m deep; another 514 specimens (241
      females and 273 males) were obtained between 2005 and 2007 from commercial
      fishery operations carried out in the same area and landings in the port of Mar
      del Plata, Argentina. Males ranged from 185 to 1250 mm total length (L(T) ) and
      females from 243 to 1368 mm L(T) . Length at maturity was estimated to be 980 mm
      for males and 1089 mm L(T)  for females. Lack of variation of testis mass
      together with the continuous production of mature spermatocyst and spermatozoa in
      deferent ducts suggested that males can reproduce throughout the year. Females
      reproduced year-round with peaks of reproductive activity an integral part of a
      continuous cycle. This conclusion is corroborated by the seasonal variation of
      ovaries, oviducal gland and the occurrence of females with eggs in the uterus
      throughout the year. Results from this study indicate that A. castelnaui is very
      susceptible to fishery pressure.

PMID- 22650425
TI  - Effect of acclimation temperature on the upper thermal tolerance of Colorado
      River cutthroat trout Oncorhynchus clarkii pleuriticus: thermal limits of a North
      American salmonid.
AB  - In an effort to explore the thermal limitations of Colorado River cutthroat trout
      Oncorhynchus clarkii pleuriticus, the critical thermal maxima (T(cmax) ) of 1+
      year Lake Nanita strain O. c. pleuriticus were evaluated when acclimated to 10,
      15 and 20 degrees  C. The mean +/-s.d.T(cmax) for O. c. pleuriticus acclimated to
      10 degrees  C was 24.6 +/- 2.0 degrees C (n = 30), for 15 degrees  C-acclimated
      fish was 26.9 +/- 1.5 degrees  C (n = 23) and for 20 degrees  C-acclimated fish
      was 29.4 +/- 1.1 degrees  C (n = 28); these results showed a marked thermal
      acclimation effect (Q10 = 1.20). Interestingly, there was a size effect within
      treatments, wherein the T(cmax) of larger fish was significantly lower than that
      of smaller fish acclimated to the same temperature. The critical thermal
      tolerances of age 0 year O. c. pleuriticus were also evaluated from three
      separate populations: Lake Nanita, Trapper Creek and Carr Creek reared under
      'common-garden' conditions prior to thermal acclimation. The Trapper Creek
      population had significantly warmer T(cmax) than the Lake Nanita population, but
      that of the Carr Creek fish had T(cmax) similar to both Trapper Creek and Lake
      Nanita fish. A comparison of these O. c. pleuriticus T(cmax) results with those
      of other stream-dwelling salmonids suggested that O. c. pleuriticus are less
      resistant to rapid thermal fluctuations when acclimated to cold temperatures, but
      can tolerate similar temperatures when acclimated to warmer temperatures.

PMID- 22650426
TI  - Genetic divergence among invasive and native populations of Plagioscion
      squamosissimus (Perciformes, Sciaenidae) in Neotropical regions.
AB  - The genetic divergence among invasive and native populations of Plagioscion
      squamosissimus from four Neotropical hydrographic basins was assessed using the
      hypervariable domain of the mitochondrial DNA (mtDNA) control region. Plagioscion
      squamosissimus is native to the neighbouring hydrographic basins of the Parnaiba
      and Amazon Rivers, and the latter includes the Araguaia-Tocantins drainage, but
      it is invasive in other basins due to introductions. The mtDNA nucleotide
      polymorphism supported the hypothesis that the Amazon and Parnaiba populations
      constitute the same species and are separated into two independent evolutionary
      lineages. Absence of nucleotide polymorphism was observed within and among P.
      squamosissimus populations invasive to the uppper and middle Parana River basins.
      Nucleotide divergence was null or low comparing the Parana invasive populations
      with the populations native to the Parnaiba River basin, whereas it was
      significantly high compared to Tocantins populations. These results ascertain
      that P. squamosissimus populations invasive to the upper Parana River basin and
      to the middle Parana River basin downstream of the Itaipu dam are derived from
      the Parnaiba River basin. The genetic data presented are potentially useful to
      assist further studies on P. squamosissimus taxonomic and geographic
      distribution, development of ecological guidelines for managing populations
      invasive to the upper Parana River basin and for preservation of native fish
      diversity.

PMID- 22650427
TI  - Dietary ontogeny and niche shift to piscivory in lacustrine brown trout Salmo
      trutta revealed by stomach content and stable isotope analyses.
AB  - The feeding ecology and ontogeny of a large size range of brown trout Salmo
      trutta in Lake Fyresvatnet, southern Norway, were examined by stomach content and
      stable isotope analyses. According to the stomach contents, the S. trutta changed
      their diet at c. 30 cm total length (L(T) ). The smaller size classes fed on
      benthic invertebrates and surface insects, whereas larger S. trutta (>30 cm) fed
      mainly on whitefish Coregonus lavaretus. A similar, but more gradual shift to
      piscivory in the size range 25-30 cm was found when using the stable isotope
      mixing model SIAR to reveal dietary ontogeny. The delta13C isotopic signature
      confirmed that S. trutta independent of size predominantly relied upon benthic
      energy sources, suggesting that the littoral zone was the primary foraging
      habitat for both invertebrate and piscivorous feeders. The delta15N values and
      trophic position increased with predator length, ranging from an average of 3.60
      for small-sized S. trutta (<15 cm) to 4.15 for large-sized fish (>35 cm). The S.
      trutta exhibited a relatively slow growth rate during the predominant
      invertebrate feeding stages up to 7 years of age and 28 cm L(T) , whereas fish
      above this size and age displayed a rapid growth rate of 9-11 cm year-1,
      demonstrating the profitability of piscivorous feeding.

PMID- 22650428
TI  - Molecular phylogeny of four morphologically similar Ostorhinchus taxa with
      specific comments on O. cf. properuptus dotted type.
AB  - In this study, the partial mtDNA 16s rRNA gene and the S7 nuclear intron were
      used to resolve the phylogenetic relationship of four morphologically similar
      members of Ostorhinchus, including two colour morphs of Ostorhinchus properuptus
      (lined and dotted types), Ostorhinchus cyanosoma and Ostorhinchus holotaenia. Two
      different tree-building methods, maximum likelihood (ML) and a Bayesian-based
      method, yielded trees with highly similar topologies and high bootstrap values
      and posterior probabilities on the main nodes. Two main clades were recovered,
      suggesting that O. properuptus dotted type is closely related to O. holotaenia,
      and O. properuptus lined type members with O. cyanosoma. In addition, the genetic
      distance between the dotted and lined types of O. properuptus (0.299) was 23-fold
      higher than that between the dotted type and O. holotaenia (0.013). The dotted
      type can be identified by genetics as slightly differentiated in Japanese waters.
      It is treated as a population of the widespread species O. holotaenia.

PMID- 22650430
TI  - Maximum sustainable speed, energetics and swimming kinematics of a tropical
      carangid fish, the green jack Caranx caballus.
AB  - Maximum sustained swimming speeds, swimming energetics and swimming kinematics
      were measured in the green jack Caranx caballus (Teleostei: Carangidae) using a
      41 l temperature-controlled, Brett-type swimming-tunnel respirometer. In
      individual C. caballus [mean +/-s.d. of 22.1 +/- 2.2 cm fork length (L(F) ), 190
      +/- 61 g, n = 11] at 27.2 +/- 0.7 degrees  C, mean critical speed (U(crit)) was
      102.5 +/- 13.7 cm s-1 or 4.6 +/- 0.9 L(F) s-1. The maximum speed that was
      maintained for a 30 min period while swimming steadily using the slow, oxidative
      locomotor muscle (U(max,c)) was 99.4 +/- 14.4 cm s-1 or 4.5 +/- 0.9 L(F) s-1.
      Oxygen consumption rate (M in mg O2 min-1) increased with swimming speed and with
      fish mass, but mass-specific M (mg O2 kg-1 h-1) as a function of relative speed
      (L(F) s-1) did not vary significantly with fish size. Mean standard metabolic
      rate (R(S) ) was 170 +/- 38 mg O2 kg-1 h-1, and the mean ratio of M at U(max,c)
      to R(S) , an estimate of factorial aerobic scope, was 3.6 +/- 1.0. The optimal
      speed (U(opt) ), at which the gross cost of transport was a minimum of 2.14 J kg
      1 m-1, was 3.8 L(F) s-1. In a subset of the fish studied (19.7-22.7 cm L(F) , 106
      164 g, n = 5), the swimming kinematic variables of tailbeat frequency, yaw and
      stride length all increased significantly with swimming speed but not fish size,
      whereas tailbeat amplitude varied significantly with speed, fish mass and L(F) .
      The mean propulsive wavelength was 86.7 +/- 5.6 %L(F) or 73.7 +/- 5.2 %L(T) .
      Mean +/-s.d. yaw and tailbeat amplitude values, calculated from lateral
      displacement of each intervertebral joint during a complete tailbeat cycle in
      three C. caballus (19.7, 21.6 and 22.7 cm L(F) ; 23.4, 25.3 and 26.4 cm L(T) ),
      were 4.6 +/- 0.1 and 17.1 +/- 2.2 %L(T) , respectively. Overall, the sustained
      swimming performance, energetics, kinematics, lateral displacement and
      intervertebral bending angles measured in C. caballus were similar to those of
      other active ectothermic fishes that have been studied, and C. caballus was more
      similar to the chub mackerel Scomber japonicus than to the kawakawa tuna
      Euthynnus affinis.

PMID- 22650429
TI  - Does spatial variation in egg thiamine and fatty-acid concentration of Lake
      Michigan lake trout Salvelinus namaycush lead to differential early mortality
      syndrome and yolk oedema mortality in offspring?
AB  - Individual variation in fatty-acid and thiamine concentrations were determined in
      lake trout Salvelinus namaycush eggs collected at two spawning grounds in Lake
      Michigan. A suite of predictor variables, including spawning location, egg fatty
      acid and thiamine concentrations, were used to attempt to explain cause-and
      effect in early life stage mortality among S. namaycush families. Lipid and fatty
      acid composition of S. namaycush eggs differed between spawning locations.
      Salvelinus namaycush offspring from south-western Lake Michigan were affected by
      a high occurrence of yolk oedema, whereas a higher frequency of early mortality
      syndrome (EMS) was observed among offspring from the north-western part of the
      lake. Random-forest regressions revealed location as the most influential
      predictor of yolk oedema mortality, whereas thiamine level in eggs was the
      strongest predictor of EMS-related mortality. Several polyunsaturated fatty acids
      were also found to be predictors of both mortalities. There is evidence of
      spatial variability in egg fatty-acid concentration among S. namaycush in Lake
      Michigan that, together with diminished thiamine concentration, contribute to low
      survival of S. namaycush progeny.

PMID- 22650431
TI  - Behaviour of fish by-catch in the mouth of a crustacean trawl.
AB  - The behaviour of fish by-catch was recorded and characterized by in situ
      observations in the mouth of a crustacean trawl using an underwater camera system
      with artificial light, at depths between 106 and 461 m, along the central coast
      of Chile. The groups or species studied were rattails (family Macrouridae),
      Chilean hake Merluccius gayi gayi, sharks (orders Carcharhiniformes and
      Squaliformes), skates (family Rajidae), flatfishes (genus Hippoglossina) and
      small benthopelagic and demersal fishes (orders Osmeriformes, Stomiiformes,
      Gadiformes, Ophidiiformes and Perciformes). The fish behaviour was categorized in
      terms of (1) position in the water column, (2) initial orientation with respect
      to the trawl, (3) locomotion and (4) swimming speed with respect to the trawl.
      Rattails, sharks, skates and flatfishes were passive in response to the trawl and
      showed similar behavioural patterns, with most fishes observed sitting or
      touching the bottom with no swimming or other activity. Merluccius gayi gayi was
      the most active species, displaying a wide combination of behavioural responses
      when the trawl approached. This species showed several behavioural patterns,
      mainly characterized by swimming forward at variable speed. A fraction of small
      bentho-pelagic and demersal fishes also showed an active behaviour but always at
      lower speed than the trawl. The species-specific differences in behaviour in the
      mouth of the trawl suggest that improvements at the level of the footrope can be
      made to reduce by-catch, especially of passive species.

PMID- 22650432
TI  - Feeding ecology of indigenous and non-indigenous fish species within the family
      Sphyraenidae.
AB  - The feeding ecology of two common indigenous (Sphyraena viridensis and Sphyraena
      sphyraena) and one abundant non-indigenous sphyraenid species, Sphyraena
      chrysotaenia, of Indo-Pacific Ocean origin, was investigated in an area of the
      eastern Mediterranean Sea. The stomach contents of 738 individuals of varying
      size, collected during the period December 2008 to August 2009, were examined.
      The dietary analyses revealed that all three species were specialized piscivores
      with a diet consisting of >90% fish, both by number and mass. Concurrent sampling
      of the fish assemblage made it possible to calculate selectivity as well as diet
      breadth and overlap of these strict piscivores. Even though several prey species
      were found in the stomachs of the three predators examined, selectivity towards
      Atherina boyeri was highly significant. For all species examined, >70% of the
      diet by mass was made up by three indigenous species of commercial value: Spicara
      smaris, Boops boops and A. boyeri. Diet breadth and size of prey increased with
      increasing body size for all predators. With increased body size, the diet
      overlap between indigenous and non-indigenous species decreased. This could be
      attributed to increased diet breadth and the specific life-history
      characteristics of indigenous species developing into larger individuals. During
      winter, the condition factor of the non-indigenous species was significantly
      lower than that of the indigenous, indicating that winter conditions in the
      Mediterranean Sea may limit its further expansion north and westward. With this
      study, the gap in knowledge of the feeding preferences of the most abundant
      piscivorous species found in coastal areas of the study region is filled.
      Additionally, the results indicate that non-indigenous species familial
      affiliation to indigenous ones does not facilitate invasion success.

PMID- 22650433
TI  - Molecular phylogenetic relationships of pangasiid and schilbid catfishes in
      Thailand.
AB  - In this study, the phylogenetic relationships among 13 pangasiids and six
      schilbids of Thailand were reconstructed based on the almost complete
      mitochondrial cytochrome b (cyt b), 12S rRNA, tRNA-Val and 16S rRNA, as well as
      the partial nuclear recombination-activating gene 1 (rag1) sequences by using the
      maximum likelihood and the Bayesian inference methods of phylogenetic
      reconstruction. The reconstructed phylogeny based on the concatenated sequence
      data set recovered Pangasiidae and Schilbidae as reciprocally monophyletic
      groups. Within Pangasiidae, four major clades were recovered, which according to
      the cyt b genetic distances can be categorized into four genera: Pangasius,
      Pseudolais, Helicophagus and Pangasianodon. The genus Pangasianodon was strongly
      supported as the most basal taxon within pangasiids, whereas Pseudolais +
      Helicophagus were recovered as a sister group of Pangasius. Within the latter,
      the giant pangasius Pangasius sanitwongsei was recovered as a sister group of the
      spot pangasius Pangasius larnaudii, Pangasius krempfi as a sister group of
      Pangasius nasutus + Pangasius conchophilus and Pangasius polyuranodon as a sister
      species of Pangasius macronema. Other internal phylogenetic relationships,
      however, were unresolved. Within Schilbidae, Pseudeutropius was supported as the
      most basal lineage. Eutropiichthys was recovered as a sister group of Clupisoma.
      The enigmatic Clupisoma sinense was recognized as more closely related to Laides
      longibarbis than to Clupisoma prateri. Thus, based on the cyt b genetic
      distances, a recategorization of C. sinense to the genus Laides is suggested. On
      the basis of a relaxed clock fossil calibration, the divergence of pangasiids and
      schilbids was estimated to have occurred 14.93 million years before present
      (b.p.) during the Miocene epoch. The separation between Pangasiidae and
      Schilbidae took place c. 13.12 Mb.p. during the early middle Miocene. The
      estimated divergence time of pangasiids is similar to the age of the calibrated
      fossil, Cetopangasius chaetobranchus, which was discovered in north-central
      Thailand. This suggests that the oldest pangasiid ancestor diverged into diverse
      genera in the area.

PMID- 22650434
TI  - Diet overlap among flatfish species in the southern North Sea.
AB  - The diets of two non-commercial flatfish species (solenette Buglossidium luteum
      and scaldfish Arnoglossus laterna) and two commercial flatfish species (dab
      Limanda limanda and plaice Pleuronectes platessa) were compared in a study area
      in the German Bight (southern North Sea) to investigate prey-resource
      partitioning between these species. The diets of A. laterna and B. luteum mainly
      comprised crustaceans (harpacticoids, amphipods, cumaceans and decapods), whereas
      the diet of L. limanda and P. platessa consisted mainly of polychaetes. The
      Schoener index, calculated for different fish size classes between these flatfish
      species, showed a biologically significant diet overlap between small-sized L.
      limanda and P. platessa and B. luteum and A. laterna, using similar prey
      resources of smaller prey (e.g. amphipods, harpacticoids and juvenile bivalves).
      In contrast, with increasing body size, a change in the diet of L. limanda and P.
      platessa towards larger prey occurred (e.g. polychaetes and decapods), resulting
      in low diet overlap values with B. luteum and A. laterna. Due to these size
      related differences in resource use, it is assumed that there is reduced
      interspecific competition for prey between larger L. limanda and P. platessa and
      both non-commercial flatfishes, probably facilitating resource partitioning
      within the same area. In contrast, smaller L. limanda and P. platessa may compete
      directly for the same prey resources with B. luteum and A. laterna. Furthermore,
      prey availability of most important prey items of the studied flatfishes was
      relatively low in the study area. Therefore, increasing abundances of B. luteum
      and A. laterna in the southern North Sea since the late 1980s, owing to fishing
      effects and climate change, might affect the population dynamics of L. limanda
      and P. platessa.

PMID- 22650435
TI  - Molecular identification of hybrids of the invasive gibel carp Carassius auratus
      gibelio and crucian carp Carassius carassius in Swedish waters.
AB  - Both mitochondrial DNA sequence and two nuclear microsatellite markers were used
      to confirm the identity of the first record of Carassius auratus gibelio in the
      western (Swedish) Baltic Sea region. A total of 49 fishes were analysed, where 22
      were from three Swedish sites connected to the Baltic Sea. The D-loop
      mitochondrial DNA sequences showed that 16 of 22 Swedish fishes were related to
      C. a. gibelio. The phylogenetic analysis of these sequences showed that these
      fish are probably not native, but represent different lineages of C. a. gibelio
      from China, Japan and Russia. All except three of these 16 fishes had
      microsatellite alleles suggesting hybridization with Carassius carassius. These
      findings suggest that a cryptic invasion of C. a. gibelio might be in progress.

PMID- 22650436
TI  - Identification and expression profiles of grass carp Ctenopharyngodon idella tlr7
      in responses to double-stranded RNA and virus infection.
AB  - The toll-like receptor 7 (tlr7) gene was identified and characterized from grass
      carp Ctenopharyngodon idella (designated as citlr7), and the messenger (m)RNA
      expression profiles were examined in vivo and in vitro. The citlr7 genomic
      sequence consists of 4276 nucleotides (nts), including two exons and one intron.
      The full length of citlr7 complementary (c)DNA sequence is 3354 nts with the
      longest open reading frame (ORF) of 3156 nts encoding a peptide of 1051 amino
      acids. citlr7 mRNA expression was high in spleen, skin and heart, and low in
      hepatopancreas, muscle, head kidney and trunk kidney in healthy fish. The
      expression of citlr7 was rapidly and significantly up-regulated at 6 h after
      grass carp reovirus (GCRV) injection (72.91 fold, P < 0.05), and recovered to the
      original level at 24 h post-injection in the spleen. The citlr7 transcript was
      rapidly and significantly down-regulated at the 6 h time point (0.32 fold, P <
      0.05) and retrieved the normal level at 72 h post-injection in the
      hepatopancreas. The citlr7 transcripts were rapidly and significantly inhibited
      at 2 h post-GCRV infection in the C. idella kidney (CIK) cell line (0.62 fold, P
      < 0.05), and were rapidly and significantly elevated by the stimulation of the
      synthetic double-stranded RNA polyriboinosinic-polyribocytidylic acid sodium salt
      [poly(I:C)] in CIK in a dose and time-dependent manner (P < 0.05). The results
      imply that citlr7 is involved in the responses to double-stranded RNA and virus
      infection.

PMID- 22650438
TI  - The reproductive behaviour of Pogonophryne scotti confirms widespread egg
      guarding parental care among Antarctic notothenioids.
AB  - In this paper, the first documentation of egg-guarding behaviour in an
      artedidraconid species, Pogonophryne scotti, through in situ photographic imagery
      obtained during video transects is provided. The male specimen was observed
      closely guarding a well-defined multi-layered egg mass deposited on the sea floor
      at 240 m on the southern South Orkney Islands shelf in the northern Weddell Sea.
      Egg-guarding parental care is present in species that are distributed among all
      of the major lineages of Antarctic notothenioids; however, lack of information on
      egg-deposition behaviours in Bovichtidae and Pseudaphritis prevents assessment of
      whether parental care originated prior to the origin of the Antarctic
      notothenioid radiation.

PMID- 22650437
TI  - Does light explain damselfish Chromis viridis abundances observed over coral
      colonies?
AB  - A single autonomous video camera was used to record the abundances of Chromis
      viridis over a branching Acropora sp. colony eight times per day over a period of
      50 days. The poor explanatory power of global radiation suggests the need for
      recording the light really available to the fish, especially in the UV range. The
      increasing number of C. viridis observed with increasing wind along shore and
      water level may correspond to individuals swimming further from their shelter in
      order to get closer to the food carried by the water currents.

PMID- 22650439
TI  - The effect of hypoxia on ventilation frequency in startled common sole Solea
      solea.
AB  - Ventilation frequency (F(V) ) in motionless common sole Solea solea was measured
      before and after a startling stimulus in normoxia and in hypoxia (15% air
      saturation). Startling reduced F(V) in normoxia (from mean +/-s.e. 41 +/- 3.3
      beats min-1 to near zero, i.e. 2.0 +/- 1.8 beats min-1) and in hypoxia (from mean
      +/-s.e. 80 +/- 4.4 to 58.8 +/- 12.9 beats min-1). It is suggested that the
      maintenance of high F(V) in hypoxia may increase the probability of detection by
      predators compared to normoxia.

PMID- 22650440
TI  - Identification and characterization of polymorphic microsatellite loci in the
      blue shark Prionace glauca, and cross-amplification in other shark species.
AB  - Two to 14 alleles were found to be segregating per locus (mean 5.2), with
      observed and expected heterozygosities ranging from 0.08 to 0.78 and 0.08 to
      0.94, respectively. Cross-amplification of six of these microsatellite loci
      indicated that they are also polymorphic in three species of Carcharhiniformes
      and two species of Lamniformes. The newly developed primers reported here
      constitute a useful tool for genetic population analyses on Prionace glauca and,
      potentially, other related species.

PMID- 22650442
TI  - Early manifestations of manual specialisation in infants: a longitudinal study
      from 20 to 30 weeks.
AB  - This longitudinal study examined lateral differences between latency time of the
      two hands during the development of prehension in 12 infants from 20 to 30 weeks.
      Latency time (LT) is defined as the delay between the visual localisation of a
      reachable target and the beginning of the movement and could be considered as a
      phase in the preparation of action. If LT varies with the hand used and the type
      of movement, this would suggest differences in information processing (nature
      and/or quantity). Results show that the latency time is shorter for the left hand
      approach movements and shorter for the right hand grasping movements. These
      findings are in favour of a manual specialisation--clearly present from 20 weeks-
      and are discussed in a possible hemispheric specialisation perspective.

PMID- 22650444
TI  - Intestinal toxicity evaluation of TiO2 degraded surface-treated nanoparticles: a
      combined physico-chemical and toxicogenomics approach in caco-2 cells.
AB  - BACKGROUND: Titanium dioxide (TiO2) nanoparticles (NPs) are widely used due to
      their specific properties, like UV filters in sunscreen. In that particular case
      TiO2 NPs are surface modified to avoid photocatalytic effects. These surface
      treated nanoparticles (STNPs) spread in the environment and might release NPs as
      degradation residues. Indeed, degradation by the environment (exposure to UV,
      water and air contact ...) will occur and could profoundly alter the
      physicochemical properties of STNPs such as chemistry, size, shape, surface
      structure and dispersion that are important parameters for toxicity. Although the
      toxicity of surface unmodified TiO2 NPs has been documented, nothing was done
      about degraded TiO2 STNPs which are the most likely to be encountered in
      environment. The superoxide production by aged STNPs suspensions was tested and
      compared to surface unmodified TiO2 NPs. We investigated the possible toxicity of
      commercialized STNPs, degraded by environmental conditions, on human intestinal
      epithelial cells. STNPs sizes and shape were characterized and viability tests
      were performed on Caco-2 cells exposed to STNPs. The exposed cells were imaged
      with SEM and STNPs internalization was researched by TEM. Gene expression
      microarray analyses were performed to look for potential changes in cellular
      functions. RESULTS: The production of reactive oxygen species was detected with
      surface unmodified TiO2 NPs but not with STNPs or their residues. Through three
      different toxicity assays, the STNPs tested, which have a strong tendency to
      aggregate in complex media, showed no toxic effect in Caco-2 cells after
      exposures to STNPs up to 100 MUg/mL over 4 h, 24 h and 72 h. The cell morphology
      remained intact, attested by SEM, and internalization of STNPs was not seen by
      TEM. Moreover gene expression analysis using pangenomic oligomicroarrays (4x
      44000 genes) did not show any change versus unexposed cells after exposure to 10
      MUg/ mL, which is much higher than potential environmental concentrations.
      CONCLUSIONS: TiO2 STNPs, degraded or not, are not harmful to Caco-2 cells and are
      unlikely to penetrate the body via oral route. It is likely that the strong
      persistence of the aluminium hydroxide layer surrounding these nanoparticles
      protects the cells from a direct contact with the potentially phototoxic TiO2
      core.

PMID- 22650445
TI  - Polarizability, ionization potential, and softness of water and methanol
      clusters: an interrelation.
AB  - The properties of methanol clusters [(CH(3)OH)(n), n = 1-12] have been studied by
      using ab initio electronic structure calculations with reference to the
      aggregation number dependence of several reactivity descriptors, such as
      ionization potential, electron affinity, polarizability, hardness, and binding
      energy. A good correlation between the dipole polarizability and the ionization
      potential of these hydrogen-bonded molecular clusters is shown to exist. The
      softness parameter has also been shown to correlate strongly with the dipole
      polarizability of these molecular clusters. Similar good correlations are also
      demonstrated to exist for water clusters [(H(2)O)(n), n = 1-20]. This work can
      thus be useful for calculating the polarizability of larger methanol or water
      clusters in terms of the corresponding ionization potential.

PMID- 22650446
TI  - Transcriptome changes after genome-wide admixture in invasive sculpins (Cottus).
AB  - Models on hybrid speciation assume that hybridization generates increased
      phenotypic variance that is utilized to invade new adaptive peaks. We test to
      what extent this prediction can be traced using gene expression data in the fish
      species Cottus perifretum and Cottus rhenanus as well as a natural hybrid lineage
      referred to as invasive sculpins. In addition, interspecies crosses were used to
      explore evolutionary trajectories from initial stages to the hybrid lineage. EST
      (expressed sequence tag) libraries were sequenced to design an oligonucleotide
      microarray that was calibrated for probe-specific differences in binding
      behaviour. Levels of gene expression divergence between species correlate with
      genetic divergence at neutral markers and, accordingly, invasive sculpins were
      intermediate between the parental species overall. However, the hybrid lineage is
      distinguished through unique patterns of gene expression that are enriched for
      biological functions which represent candidates for the fitness properties of
      invasive sculpins. We compare F(2)  crosses with natural invasive sculpins to
      show that the variance in gene expression decreases in invasives. Moreover, few
      of the transgressive patterns of gene expression that distinguish invasives can
      be directly observed in F(2)  crosses. This suggests that the invasive
      transcriptome was subject to secondary changes after admixture. The result is in
      line with an evolutionary process that reduces maladaptive variance and optimizes
      the phenotype of an emerging hybrid lineage.

PMID- 22650447
TI  - Occupational exposure during pregnancy and the risk of hay fever in 7-year-old
      children.
AB  - OBJECTIVES: The prevalence of allergic diseases including hay fever has increased
      in the last decades, especially in Westernised countries. The aim of this study
      was to analyse whether occupational exposure during pregnancy is associated with
      development of hay fever in 7-year-old Danish children. METHODS: A total of
      42,696 women and their children from the Danish National Birth Cohort were
      categorised according to maternal occupational exposure. Exposure information was
      obtained by combining job title in pregnancy with a commonly used asthma Job
      Exposure Matrix. Information on hay fever in the child was obtained by an
      internet questionnaire at follow-up at 7 years of age. RESULTS: Adjusted logistic
      regression analyses showed no significant association between maternal
      occupational exposure during pregnancy and hay fever among the 7-year-old
      children. Stratifying for atopic status in the children did not change the
      results. The prevalence of hay fever was 10.0% in the atopic children compared
      with 3.6% in the non-atopic children. Maternal atopic disposition increased the
      risk of hay fever in the offspring, odds ratio (OR) 2.49 [95% confidence interval
      (CI) 2.26; 2.74]. Rural residence during pregnancy decreased the risk for hay
      fever [OR 0.74 (95% CI 0.59; 0.92)] as did parity, OR 0.72 (95% CI 0.66; 0.80)
      and 0.70 (95% CI 0.48; 1.00) for 2nd and 3rd child, respectively, compared with
      the firstborn child. CONCLUSION: The results suggest that occupational exposure
      among pregnant women in Denmark is not a risk factor for hay fever among young
      children.

PMID- 22650448
TI  - Has the time to come leave the "watch-and-wait" strategy in newly diagnosed
      asymptomatic follicular lymphoma patients?
AB  - BACKGROUND: Historically, the median overall survival for follicular lymphoma
      (FL) has been considered to be 9-10 years, and no treatment had ever prolonged
      this time period. Studies conducted more than 20 years ago demonstrated that
      treating patients with asymptomatic FL at the onset of the disease did not
      increase their survival, and that almost 20% of these patients did not need any
      treatment in the first 10 years of follow-up. Based on these facts, most clinical
      practice guidelines recommend active surveillance policies for patients with
      asymptomatic FL. DISCUSSION: The introduction of antiCD-20 monoclonal antibodies,
      over the last 15 years, has significantly increased the median survival rate to
      above 14 years. This improvement was achieved before the combination of rituximab
      and chemotherapy regimens became extensively used in patients with symptomatic
      disease. Therefore, this increase in survival may currently be more significant.
      At present, several clinical trials have evaluated low-toxicity therapies that
      prolong progression-free periods, among which rituximab monotherapy,
      radioimmunotherapy or the combination of rituximab with bendamustine are the most
      relevant. Unfortunately, these clinical trials have included only patients with
      symptomatic FL. The results of a recently reported clinical trial show that
      treatment with single-agent rituximab prolongs progression-free survival rates,
      time to new treatment and the quality of life of asymptomatic patients, as
      compared with the active surveillance strategy. Longer follow-up of these results
      and data regarding overall survival are awaited before this treatment can be
      recommended as the standard initial therapy. SUMMARY: There are different
      therapeutic possibilities for asymptomatic FL patients, but no data are currently
      available to indicate which option is the best. Patients need to understand the
      risks and benefits of observation versus treatment before a final decision can be
      made. For patients who want active treatment the administration of four weekly
      rituximab doses should be considered.

PMID- 22650449
TI  - Update on biomarkers of acute kidney injury: moving closer to clinical impact?
AB  - Acute kidney injury (AKI) represents a common disorder in hospitalized patients,
      and its incidence is rising at an alarming rate. Despite significant improvements
      in critical care and renal replacement therapies (RRT), the outcome of critically
      ill patients with AKI necessitating RRT remains unacceptably dismal. In current
      clinical practice, the diagnosis and severity classification of AKI is based on a
      rise in serum creatinine levels, which may occur 2-3 days after the initiating
      renal insult and delay potentially effective therapies that are limited to the
      early stage. The emergence of numerous renal tubular damage-specific biomarkers
      offers an opportunity to diagnose AKI at an early timepoint, to facilitate
      differential diagnosis of structural and functional AKI, and to predict the
      outcome of established AKI. The purposes of this review are to summarize and to
      discuss the performance of these novel AKI biomarkers in various clinical
      settings. The most promising AKI biomarkers include plasma and urinary neutrophil
      gelatinase-associated lipocalin (NGAL), urinary interleukin (IL)-18, urinary
      liver-type fatty acid binding protein (L-FABP), urinary cystatin C, and urinary
      kidney injury molecule (KIM)-1. However, enthusiasm about their usefulness in the
      emergency department seems unwarranted at present. There is little doubt that
      urinary biomarkers of nephron damage may enable prospective diagnostic and
      prognostic stratification in the emergency department. However, comparison of the
      areas under the receiver-operating characteristic curves of these biomarkers with
      clinical and/or routine biochemical outcome parameters reveals that none of these
      biomarkers has a clear advantage beyond the traditional approach in clinical
      decision making in patients with AKI. The performance of various biomarkers for
      predicting AKI in patients with sepsis or with acute-on-chronic kidney disease is
      poor. The inability of biomarkers to improve classification of 'unclassifiable'
      (structural or functional) AKI, in which accurate differential diagnosis of pre
      renal versus intrinsic renal AKI has the most value, illustrates another problem.
      Future research is necessary to clarify whether serial measurements of a specific
      biomarker or the use of a panel of biomarkers may be more useful in critically
      ill patients at risk of AKI. Whether or not the use of AKI biomarkers
      revolutionizes critical care medicine by early diagnosis of severe AKI and
      individualizes the management of AKI patients remains to be shown. Currently, the
      place of biomarkers in this decision-making process is still uncertain.
      Indiscriminate use of various biomarkers may distract clinicians from adequate
      clinical evaluation, may result in worse instead of better patient outcomes, and
      may waste money. Future large randomized studies are necessary to demonstrate the
      association between biomarker levels and clinical outcomes, such as dialysis,
      clinical events, or death. It needs to be shown whether assignment to earlier
      treatment for AKI on the basis of generally accepted biomarker cut-off levels
      results in a reduction in mortality and an improvement in recovery of renal
      function.

PMID- 22650450
TI  - The case for kidney donation before end-of-life care.
AB  - Donation after cardiac death (DCD) is associated with many problems, including
      ischemic injury, high rates of delayed allograft function, and frequent organ
      discard. Furthermore, many potential DCD donors fail to progress to asystole in a
      manner that would enable safe organ transplantation and no organs are recovered.
      DCD protocols are based upon the principle that the donor must be declared dead
      prior to organ recovery. A new protocol is proposed whereby after a donor family
      agrees to withdrawal of life-sustaining treatments, premortem nephrectomy is
      performed in advance of end-of-life management. Since nephrectomy should not
      cause the donor's death, this approach satisfies the dead donor rule. The donor
      family's wishes are best met by organ donation, successful outcomes for the
      recipients, and a dignified death for the deceased. This proposal improves the
      likelihood of achieving these objectives.

PMID- 22650451
TI  - In defense of Morrissey's strategy.

PMID- 22650452
TI  - Going all the way: ethical clarity and ethical progress.

PMID- 22650453
TI  - Could premortem organ retrieval be lawful?

PMID- 22650454
TI  - Organ donation prior to death--balancing benefits and harms.

PMID- 22650455
TI  - Avoiding violation of the dead donor rule: the costs to patients.

PMID- 22650456
TI  - Antemortem donor bilateral nephrectomy: a violation of the patient's best
      interests standard.

PMID- 22650458
TI  - Ethics in HIV prevention research: clarifying the complexities.

PMID- 22650457
TI  - How good is "good enough"? The case for varying standards of evidence according
      to need for new interventions in HIV prevention.
AB  - In 2010, randomized controlled trials (RCTs) of two different biomedical
      strategies to prevent HIV infection had positive findings. However, despite
      ongoing very high levels of HIV infection in some countries and population
      groups, it has been made clear by regulatory authorities that the evidence
      remains insufficient to support either product being made available outside of
      research contexts in the developing world for at least two years. In addition,
      prevention trials in endemic areas will continue to test new interventions
      against placebo. But the judgments of evidentiary standards are never value
      neutral. Using the recent trials and their contexts as case studies, we examine
      the basis for these decisions, which will potentially delay access to scientific
      innovation to the people who are most urgently in need of it.

PMID- 22650459
TI  - The devil in the details: thorough assessment of evidence and ethics is needed in
      evaluating new HIV prevention methods.

PMID- 22650460
TI  - Evidence of efficacy and human right to health.

PMID- 22650462
TI  - Reproductive autonomy is an illusion.

PMID- 22650461
TI  - Preserving the right to future children: an ethical case analysis.
AB  - We report on the case of a 2-year-old female, the youngest person ever to undergo
      ovarian tissue cryopreservation (OTC). This patient was diagnosed with a rare
      form of sickle cell disease, which required a bone-marrow transplant, and late
      effects included high risk of future infertility or complete sterility. Ethical
      concerns are raised, as the patient's mother made the decision for OTC on the
      patient's behalf with the intention that this would secure the option of
      biological childbearing in the future. Based on Beauchamp and Childress's
      principlism approach of respect for autonomy, nonmaleficence, beneficence, and
      justice, pursing OTC was ethically justified.

PMID- 22650463
TI  - Juvenile ovarian tissue cryopreservation and social justice: an imperative to
      broaden the discussion.

PMID- 22650464
TI  - Preserving capabilities.

PMID- 22650465
TI  - The ethical status of prophylactic interventions in children: ovarian tissue
      cryopreservation and vaccination.

PMID- 22650466
TI  - The missing piece(s).

PMID- 22650467
TI  - Reframing the justice implications of preserving the right to future children.

PMID- 22650490
TI  - Graft-versus-host disease or toxic epidermal necrolysis: diagnostic dilemma after
      liver transplantation.
AB  - Graft-versus-host disease (GvHD) and toxic epidermal necrolysis (TEN) are rare
      and severe complications after liver transplantation. While mild acute GvHD is
      quite different from TEN and easy to distinguish, severe acute GvHD and TEN can
      be hard to differentiate because of similar clinical symptoms. We herein report a
      case with rapid progression of critical illness, after liver transplantation,
      caused by GvHD or TEN, although between those, diagnosis was not possible during
      the clinical course. Although, based on the timing/progression of the symptoms
      and the chimerism of >40%, the case seemed much more clinically consistent with
      GVHD, the combination of clinical symptoms together with skin rashes and the
      histologic appearance of skin lesions indicated diagnosis of a Stevens-Johnson
      syndrome/TEN overlap. The true diagnostic dilemma in such cases is discussed in
      detail, as these cases emphasize the need for more advanced diagnostic
      techniques.

PMID- 22650492
TI  - Commentary: the impact of compact lipiodolisation following transarterial
      chemoembolisation for hepatocellular carcinoma.

PMID- 22650494
TI  - Letter: acute hepatitis B - to treat or not to treat?

PMID- 22650495
TI  - Letter: pathogenesis of tumour necrosis factor-alpha antagonists-induced
      psoriasiform lesions.

PMID- 22650496
TI  - Multifunctional resistive-heating and color-changing monofilaments produced by a
      single-step coaxial melt-spinning process.
AB  - Multifunctional coaxial monofilaments were successfully produced by melt-spinning
      several polymer composites in a single-step. The external layer of the
      monofilaments was a thermochromic composite having a color-transition at 40 
      degrees C (above the ambient temperature) in order to avoid control interferences
      by the external temperature. The core layer of the monofilaments was a conductive
      polymer nanocomposite whose resistive heating properties were used to control the
      monofilament's temperature and therefore its color using electrical current. The
      careful selection of the materials and adequate formulation allowed to obtain a
      trilayer structure with enhanced compatibility between the layers. The mechanical
      properties of the monofilaments were improved by a solid-state stretching step
      while also decreasing their diameter. A 64 cm(2) prototype fabric was woven to
      characterize the resistive-heating and color-changing properties of the
      monofilaments. Exceptional thermal output levels were reached, with a temperature
      rising up to over 100  degrees C at voltages above 110 V. The reversible color
      change properties were also successfully demonstrated. 

PMID- 22650601
TI  - Use of Cutometer area parameters in evaluating age-related changes in the skin
      elasticity of the cheek.
AB  - BACKGROUND/AIM: The decrease of skin elasticity on the cheek is a major concern
      to woman. The Cutometer has been widely used to evaluate skin elasticity and its
      change with aging. Cutometer parameters derived from one suction have been
      traditionally used to evaluate skin elasticity, and few reports describe the use
      of multiple suctions to obtain parameters to assess the skin elasticity of the
      cheek. To find the most suitable Cutometer parameter that reflects age-related
      changes in the elasticity of cheek skin using multiple suctions. METHODS: The
      cheeks of 32 healthy Japanese women (mean age, 42.3 years) were assessed using
      the Cutometer MPA580 by measuring the skin mechanical parameters R0-R9, F2 and
      F3. Parameters F2 and F3 were obtained by the multiple suction method. The
      relationship between age and these parameters were then examined. RESULTS:
      Significant negative correlations were found between the age of subjects and R2,
      R3, R7, R8 and F3. Of these, the correlation coefficient was best between age and
      F3 (r = -0.641), followed R8 (r = -0.603). CONCLUSION: Although R parameters have
      been used to evaluate skin elasticity, our study showed that F3 parameters
      derived from multiple suctions appear to be suitable for evaluating the
      elasticity of cheek skin, since this parameter is less influenced by
      environmental factors compared with R parameters.

PMID- 22650602
TI  - Metabolic syndrome in type 2 diabetes: comparative prevalence according to two
      sets of diagnostic criteria in sub-Saharan Africans.
AB  - BACKGROUND: Available definition criteria for metabolic syndrome (MS) have
      similarities and inconsistencies. The aim of this study was to determine the
      prevalence of MS in a group of Cameroonians with type 2 diabetes, according to
      the International Diabetes Federation (IDF) and the National Cholesterol
      Education Programme Adult Treatment Panel III (NCEP-ATP III) criteria, and to
      assess the concordance between both criteria, and the implications of combining
      them. METHODS: We collected clinical and biochemical data for 308 patients with
      type 2 diabetes (men 157) at the National Obesity Center of the Yaounde Central
      Hospital, Cameroon. Concordance was assessed with the use of the Kappa statistic.
      RESULTS: Mean age (standard deviation) was 55.8 (10.5) years and the median
      duration of diagnosed diabetes (25th-75th percentiles) was 3 years (0.5-5.0),
      similarly among men and women. The prevalence of MS was 71.7% according to the
      IDF criteria and 60.4% according to NCEP-ATP III criteria. The prevalence was
      significantly higher in women than in men independently of the criteria used
      (both p < 0.001). Overall concordance between both definitions was low to average
      0.51 (95% confidence interval: 0.41-0.61). Combining the two sets of criteria
      marginally improved the yield beyond that provided by the IDF criteria alone in
      men, but not in the overall population and in women. CONCLUSIONS: The IDF and
      NCEP-ATP III criteria do not always diagnose the same group of diabetic
      individuals with MS and combining them merely increases the yield beyond that
      provided by the IDF definition alone. This study highlights the importance of
      having a single unifying definition for MS in our setting.

PMID- 22650604
TI  - Structure-function relationship of Vibrio harveyi NADPH-flavin oxidoreductase
      FRP: essential residues Lys167 and Arg15 for NADPH binding.
AB  - Vibrio harveyi NADPH-FMN oxidoreductase (FRP) catalyzes flavin reduction by
      NADPH. In comparing amino acid sequence and crystal structure with Escherichia
      coli NfsA, residues N134, R225, R133, K167, and R15 were targeted for
      investigation of their possible roles in the binding and utilization of the NADPH
      substrate. By mutation of each of these five residues to an alanine, steady-state
      rate analyses showed that the variants K167A and R15A had apparently greatly
      increased K(m,NADPH) and reduced k(cat)/K(m,NADPH), whereas little or much more
      modest changes were found for the other variants. The deuterium isotope effects
      (D)(V/K) for (4R)-[4-(2)H]-NADPH were markedly increased to 6.3 and 7.4 for K167A
      and R15A, respectively, indicating that the rate constants for NADPH and NADP(+)
      dissociation were greatly enhanced relative to the hydride transfer steps. Also,
      anaerobic stopped-flow analyses revealed that the equilibrium dissociation
      constant for NADPH binding (K(d)) to be 2.5-3.9 and 1.1 mM for K167A and R15A,
      respectively, much higher than the 0.4 MUM K(d) for the native FRP, whereas the
      k(cat) of these two variants were similar to that of the wild-type enzyme.
      Moreover, the K167 to alanine mutation led to even a slight increase in
      k(cat)/K(m) for NADH. These results, taken together, provide a strong support to
      the conclusion that K167 and R15 each was critical in the binding of NADPH by
      FRP. Such a functional role may also exist for other FRP homologous proteins.

PMID- 22650605
TI  - Phonons in slow motion: dispersion relations in ultrathin Si membranes.
AB  - We report the changes in dispersion relations of hypersonic acoustic phonons in
      free-standing silicon membranes as thin as ~8 nm. We observe a reduction of the
      phase and group velocities of the fundamental flexural mode by more than 1 order
      of magnitude compared to bulk values. The modification of the dispersion relation
      in nanostructures has important consequences for noise control in nano- and
      microelectromechanical systems (MEMS/NEMS) as well as opto-mechanical devices.

PMID- 22650606
TI  - Using antibodies to target cancer therapeutics.
AB  - INTRODUCTION: Over a half a century ago, radiolabeled antibodies were shown to
      localize selectively in tissues based on the expression of unique antigens.
      Antibodies have since become the de facto targeting agent, even inspiring the
      development of non-antibody compounds for targeting purposes. AREAS COVERED: In
      this article, we review various aspects of how antibodies are transforming the
      way cancer is being detected and treated, with the growing demand for
      unconjugated and many new antibody conjugates. While unconjugated antibodies
      continue to garner most of the attention, interest in new antibody drug
      conjugates and immunotoxins has expanded over the past few years. However, there
      continues to be active research with new radioimmunoconjugates for imaging and
      therapy, particularly with alpha-emitters, as well as antibody-targeted cytokines
      and other biological response modifiers. EXPERT OPINION: The increasing number of
      new agents being developed and tested clinically suggests that antibody-targeted
      compounds will have an expanding role in the future.

PMID- 22650607
TI  - Intradermal DNA vaccination enhanced by low-current electroporation improves
      antigen expression and induces robust cellular and humoral immune responses.
AB  - DNA represents an ideal vaccine platform for HIV and many infectious diseases
      because of its safety, stability, and ease of manufacture. However, the
      immunogenicity of DNA vaccines has traditionally been low compared with viral
      vectors, recombinant protein, and live attenuated vaccines. The immunogenicity of
      DNA vaccines has been significantly enhanced by delivery with in vivo
      electroporation. Further improvements now allow electroporation to be performed
      in the dermis, which could potentially improve patient tolerability and may
      further enhance immunogenicity. In this study we examined how the current of
      intradermal vaccination impacts antigen expression, inflammation, and the
      induction of both humoral and cellular immunity in guinea pigs and nonhuman
      primates. We observed that a lower (0.1 A) current reduced inflammation and
      improved antigen expression compared with a 0.2 A current. The improved antigen
      expression resulted in a trend toward higher cellular immune responses but no
      impact on HIV- and influenza-specific binding titers. This study highlights the
      need for optimization of electroporation conditions in vivo in order to balance
      enhanced plasmid transfection with a loss of expression due to tissue
      inflammation and necrosis. These results suggest that a lower, 0.1-A current may
      not only improve patient tolerability but also improve immunogenicity.

PMID- 22650608
TI  - Modification of nitrile-terminated biphenylthiol self-assembled monolayers by
      electron irradiation and related applications.
AB  - Here we describe the behavior of self-assembled monolayers (SAMs) of 4'
      cyanobiphenyl-4-thiol (CBPT) on Au(111) upon electron irradiation. Under such a
      treatment, the aromatic framework of CBPT SAMs is laterally cross-linked while
      the nitrile groups, located at the SAM-ambience interface, are reduced to active
      amine moieties which can be used as docking sites for the coupling of other
      species. This makes CBPT monolayers as a promising system for conventional and
      chemical lithography as well as for nanofabrication. Along these lines, we
      demonstrate the preparation of complex polymer brushes, patterning of the
      underlying substrate, and fabrication of molecule-thin, free-standing membranes
      on the basis of CBPT SAMs. The balance between the application-favorable
      processes and defragmentation in these films is studied in detail, and comparison
      to the well-established (for the relevant applications) system of 4'
      nitrobiphenyl-4-thiols is performed. Taking CBPT SAMs as a model system, the
      effect of the energy of the primary electrons on the extent of the chemical
      transformation and cross-linking in substituted aromatic SAMs is investigated.

PMID- 22650609
TI  - Rapid and selective separation for mixed proteins with thiol functionalized
      magnetic nanoparticles.
AB  - Thiol group functionalized silica-coated magnetic nanoparticles (Si-MNPs@SH)
      were synthesized for rapid and selective magnetic field-based separation of mixed
      proteins. The highest adsorption efficiencies of binary proteins, bovine serum
      albumin (BSA; 66 kDa; pI = 4.65) and lysozyme (LYZ; 14.3 kDa; pI = 11) were shown
      at the pH values corresponding to their own pI in the single-component protein.
      In the mixed protein, however, the adsorption performance of BSA and LYZ by Si
      MNPs@SH was governed not only by pH but also by the molecular weight of each
      protein in the mixed protein.

PMID- 22650610
TI  - The perception of attractiveness and trustworthiness in male faces affects
      hypothetical voting decisions differently in wartime and peacetime scenarios.
AB  - Facial appearance of candidates has been linked to real election outcomes. Here
      we extend these findings by examining the contributions of attractiveness and
      trustworthiness in male faces to perceived votability. We first use real faces to
      show that attractiveness and trustworthiness are positively and independently
      related to perceptions of good leadership (rating study). We then show that
      computer graphic manipulations of attractiveness and trustworthiness influence
      choice of leader (experiments 1 and 2). Finally, we show that changing context
      from wartime to peacetime can affect which face receives the most votes.
      Attractive faces were relatively more valued for wartime and trustworthy faces
      relatively more valued for peacetime (experiments 1 and 2). This pattern suggests
      that attractiveness, which may indicate health and fitness, is perceived to be a
      useful attribute in wartime leaders, whereas trustworthiness, which may indicate
      prosocial traits, is perceived to be more important during peacetime. Our studies
      highlight the possible role of facial appearance in voting behaviour and the role
      of attributions of attractiveness and trust. We also show that there may be no
      general characteristics of faces that make them perceived as the best choice of
      leader; leaders may be chosen because of characteristics that are perceived as
      the best for leaders to possess in particular situations.

PMID- 22650612
TI  - Group additivity values for estimating the enthalpy of formation of organic
      compounds: an update and reappraisal. 2. C, H, N, O, S, and halogens.
AB  - This study extends a previous publication on group additivity values (GAVs) for
      the elements C, H, and O, to include the elements nitrogen, sulfur, and the
      halogens. The present state and utility of the Benson additivity schemes for
      estimating the enthalpy of formation (Delta(f)H(0)) of organic compounds are
      again described, extending them to include more elements. Old and new GAVs for a
      wide variety of compounds are provided and are revised where necessary. When new
      terms are proposed, or old ones are significantly altered, the rationale for so
      doing is presented. GAV derived ring strain values for benzene and pyridine
      indicate that the aromatic stabilization of each is essentially the same. As
      before, the thermochemical consequences of replacing one functional group by
      another are also shown, thus permitting quick shortcuts to the estimation of new
      Delta(f)H(0) values.

PMID- 22650611
TI  - The impact of childhood acute rotavirus gastroenteritis on the parents' quality
      of life: prospective observational study in European primary care medical
      practices.
AB  - BACKGROUND: Rotavirus (RV) is the commonest cause of acute gastroenteritis in
      infants and young children worldwide. A Quality of Life study was conducted in
      primary care in three European countries as part of a larger epidemiological
      study (SPRIK) to investigate the impact of paediatric rotavirus gastroenteritis
      (RVGE) on affected children and their parents. METHODS: A self-administered
      questionnaire was linguistically validated in Spanish, Italian and Polish. The
      questionnaire was included in an observational multicentre prospective study of
      302 children aged <5 years presenting to a general practitioner or paediatrician
      for RVGE at centres in Spain, Italy or Poland. RV infection was confirmed by
      polymerase chain reaction (PCR) testing (n = 264). The questionnaire was
      validated and used to assess the emotional impact of paediatric RVGE on the
      parents. RESULTS: Questionnaire responses showed that acute RVGE in a child
      adversely affects the parents' daily life as well as the child. Parents of
      children with RVGE experience worry, distress and impact on their daily
      activities. RVGE of greater clinical severity (assessed by the Vesikari scale)
      was associated with higher parental worries due to symptoms and greater changes
      in the child's behaviour, and a trend to higher impact on parents' daily
      activities and higher parental distress, together with a higher score on the
      symptom severity scale of the questionnaire. CONCLUSIONS: Parents of a child with
      acute RVGE presenting to primary care experience worry, distress and disruptions
      to daily life as a result of the child's illness. Prevention of this disease
      through prophylactic vaccination will improve the daily lives of parents and
      children.

PMID- 22650613
TI  - Use a rabbit or a rhino to sell a carrot? The effect of character-product
      congruence on children's liking of healthy foods.
AB  - This study investigated whether unfamiliar characters are as effective as
      familiar characters in stimulating children's affective responses toward healthy
      foods. In particular, the authors investigated whether an unfamiliar character
      which is congruent with a product can be as effective as a familiar character.
      The authors tested 2 types of character-product congruence: conceptual congruence
      (on the basis of a familiar link), and perceptual congruence (on the basis of
      color similarity). In a repeated measures design, 166 children (4-6 years old)
      were exposed to a picture of a carrot combined randomly with 5 different types of
      character: an (incongruent) familiar character and four unfamiliar characters
      varying in character-product congruence (i.e., both conceptually and perceptually
      congruent, conceptual only, perceptual only, and incongruent). The authors
      measured children's automatic affective responses toward these character-product
      combinations using a time-constrained task, and elaborate affective responses
      using a nonconstrained task. Results revealed that the conceptually congruent
      unfamiliar characters were just as effective as the familiar character in
      increasing children's automatic affective responses. However, the familiar
      character triggered the most positive elaborate affective responses. Results are
      explained in light of processing fluency and parasocial relationship theories.

PMID- 22650614
TI  - Physician perceptions of pharmacist roles in a primary care setting in Qatar.
AB  - PURPOSE: Pharmacists are uniquely trained to provide guidance to patients in the
      selection of appropriate non-prescription therapy. Physicians in Qatar may not
      always recognize how pharmacists function in assuring safe medication use. Both
      these health professional groups come from heterogeneous training and experiences
      before migrating to the country and these backgrounds could influence
      collaborative patient care. Qatar Petroleum (QP), the largest private employer in
      the country, has developed a pharmacist-guided medication consulting service at
      their primary care clinics, but physician comfort with pharmacists recommending
      drug therapy is currently unknown. The objective of this study is to characterize
      physician perceptions of pharmacists and their roles in a primary care patient
      setting in Qatar. METHODS: This cross-sectional survey was developed following a
      comprehensive literature review and administered in English and Arabic.
      Consenting QP physicians were asked questions to assess experiences, comfort and
      expectations of pharmacist roles and abilities to provide medication-related
      advice and recommend and monitor therapies. RESULTS: The median age of the 62
      (77.5%) physicians who responded was between 40 and 50 years old and almost two
      third were men (64.5%). Fourteen different nationalities were represented.
      Physicians were more comfortable with pharmacist activities closely linked to
      drug products than responsibilities associated with monitoring and optimization
      of patient outcomes. Medication education (96.6%) and drug knowledge (90%) were
      practically unanimously recognized as abilities expected of pharmacists, but
      consultative roles, such as assisting in drug regimen design were less
      acknowledged. They proposed pharmacist spend more time with physicians attending
      joint meetings or education events to help advance acceptance of pharmacists in
      patient-centered care at this site. CONCLUSIONS: Physicians had low comfort and
      expectations of patient-oriented pharmacist roles but were not threatened to
      learn more about these capabilities or explore enhanced collaboration in patient
      care.

PMID- 22650615
TI  - Survival and differentiation of subspecies of the land snail Charpentieria itala
      in mountain refuges in the Southern Alps.
AB  - Two groups of subspecies of the door snail Charpentieria itala are distributed in
      a mosaic pattern in the Southern Alps. Some subspecies that morphologically
      resemble Charpentieria stenzii occur at exposed rocks at higher altitudes,
      whereas other subspecies live on more humid rocks at lower altitudes. This
      pattern can be explained by two alternative hypotheses. Either the stenzii-like
      or 'stenzioid' subspecies have a common origin and represent relicts of an early
      colonization wave that survived the ice ages in isolated mountain refuges within
      the Alps, or the geographically isolated stenzioid subspecies evolved through
      parallel adaptation of C. itala populations to life on exposed rocks. In this
      study, the first hypothesis could be supported by several lines of evidence.
      Analyses of amplified fragment length polymorphisms (AFLP) data indicated a
      common origin of the stenzioid subspecies of the Bergamasque Prealps and of the
      stenzioid subspecies of the Brescia and Garda Prealps, whereas an outlier
      analysis detected only few AFLP markers that might be under selection. High 16S
      rDNA distances between subspecies suggest that the divergence of the subspecies
      predates at least most of the glacials. The occurrences of the stenzioid
      subspecies are concentrated in mountain areas that were not glaciated during the
      Last Glacial Maximum. The genetic differentiation and the isolated distribution
      areas of the stenzioid subspecies indicate that they survived in five separate
      mountain refuges in the Bergamasque, Brescia and Garda Prealps. In addition, the
      clustering of the Charpentieria itala latestriata populations from different
      valleys indicates a low-altitude refuge.

PMID- 22650616
TI  - Clinical features of a paediatric asthma population in Trinidad.
AB  - AIM: Clinical features and management of paediatric asthma, highly prevalent in
      the Caribbean, was explored in Trinidadian children. MATERIALS: Children (2-16
      years) with acute [visiting Accident and Emergency (A&E) in the past 12 months
      (50.2%, 120)] or stable asthma [controlled during the previous 3 months (49.8%,
      119)] were studied. RESULTS: There were more (P < 0.001) boys (71.5%) than girls.
      Asthma was associated with asthmatic mothers (48.5%), fathers (19.2%) and both
      parents (15.1%) (P < 0.001). Children's average age of first wheeze was 2.5
      (standard deviation = 1.3) years; 30.1% were nebulized before 1 year. In the past
      12 months, frequencies of A&E visits were once (20.6%), >1 (61.9%) and >3 times
      (26.4%) (P < 0.001). Sufferers of exacerbations showed negative logistic
      regression for age (-0.129, standard error = 0.039, P < 0.001) independent of
      gender. Acute asthmatics who suffered cough, fever and sore throat in the
      preceding week were respectively 15.2 [odds ratio (OR) = 15.2, 95% confidence
      interval (CI) = 6.8-34.0], 13.7 (OR = 13.7, 95% CI = 6.7-28.2) and 3.4 (OR = 3.4,
      95% CI = 1.7-6.7) times more likely to suffer wheeze exacerbations than stable
      children. Most stable children (76.5%) inhaled corticosteroids with salbutamol
      reliever compared with 22.5% of acute asthmatics, whereas 40.8% of the latter
      group used salbutamol alone compared with 19.3% of stable children (P < 0.001).
      CONCLUSION: Childhood wheeze occurs before 3 years and is associated with
      maternal asthma. Cough, fever and sore throat in the previous week are strongly
      associated with exacerbations. Defining these associations could enhance
      preventive approaches to combat childhood asthma.

PMID- 22650617
TI  - Psychogeriatric care: building rural community capacity.
AB  - INTRODUCTION: Since the late 1980s, British Columbia (BC) Canada has been
      undergoing a process of regionalization of health services which includes
      decentralization and the demand for self-sufficiency with respect to caring for
      people with mental health issues. In BC, regionalization has meant the continued
      downsizing of its one large provincial psychiatric hospital Riverview, which has
      resulted in relocating patients from this hospital to cities and towns throughout
      BC, and the establishment and/or renovation of psychiatric tertiary-care
      facilities to treat local community members who experience mental ill health. In
      the context of the relocation of psychiatric tertiary care, communities in
      northern BC face the specific challenge of having to provide these specialized
      services in remote settings, not only for people transferred from Riverview, but
      also for the increasing number of people 'aging-in-place' in a region that has
      the fastest growth of older adults in BC. Little is known about the capacity of
      these remote communities to manage change, develop broader models of care, and
      integrate people with psychogeriatric mental health issues with residents at
      existing facilities. METHODS: This study employed a qualitative research design
      which involved field research in the rural community where people were
      transferred, and interviews and focus groups with key people involved in the
      transfer process. In the analysis of the data a gender-based lens was applied to
      clarify the differing needs and concerns of male and female patients and to
      attend to possible needs relating to culture and ethnicity. RESULTS: The findings
      illustrate persistent 'hinterland-metropolis' and 'front-line versus
      administrative staff' tensions, with respect to resource distribution and top
      down governance, and demonstrate the need for more transparent and comprehensive
      planning by health authorities with respect to instituting mental health reforms
      in a northern context, as well as improved communication between administrative
      and front-line staff. The research suggests that it is important to attend to the
      differing needs of women and men in the context of psychogeriatric care, as well
      as to other factors such as ethnicity and culture, in order to provide
      appropriate care. Finally, building community capacity to deal with the complex
      needs of patients is severely hampered not only by facility and regional health
      authority staff turnover, but also the stresses inherent to working in northern
      communities which include geographic, social and economic challenges. CONCLUSION:
      Increased local engagement is a way to identify and address challenges related to
      relocating psychogeriatric care to northern and remote settings, and to enhance
      psychogeriatric care provision in similar locales. While provincial and regional
      level 'big picture' planning is a necessity, study participants highlighted the
      critical role of local perspective and expertise.

PMID- 22650644
TI  - LiFePO(4) nanocrystals: liquid-phase reduction synthesis and their
      electrochemical performance.
AB  - Nanosized LiFePO4 is a kind of promising material for high performance lithium
      ion batteries; however, the synthesis of nanosized LiFePO4 still has some
      challenges in forming an orthorhombic phase in atmospheric liquid phase and
      protecting the LFP nanoparticles from aggregation, etc. In this work, LiFePO4
      nanocrystals were synthesized through a high-temperature (350  degrees C) liquid
      phase reduction method. The size and morphology of nanocrystals can be readily
      controlled by tuning the ratio of solvents, and the size-dependent behavior of
      lithium storage performance is also observed. After a carbon-coating surface
      treatment, rhombic-shaped LiFePO4 nanocrystals display excellent lithium storage
      properties with high reversible capacities and good cycle life (141.0 mAh g(-1)
      at 0.5 C after 50 cycles etc.). This method can be extended to prepare LiMnPO4
      nanorods by substituting iron source with manganese salt. 

PMID- 22650618
TI  - Rediocide A, an Insecticide, induces G-protein-coupled receptor desensitization
      via activation of conventional protein kinase C.
AB  - In order to identify small-molecule antagonists of Methuselah (Mth), a Drosophila
      G-protein-coupled receptor (GPCR) involved in life-span control, a library of
      natural compounds was screened, and it was found that rediocide A (1), a daphnane
      ester from the roots of Trigonostemon reidioides and used currently for flea
      control, potently inhibited calcium mobilization mediated by this receptor.
      Compound 1 inhibited calcium mobilization in GPCRs other than Mth, indicating
      that the inhibitory effect was not due to receptor antagonism but rather to a
      more general mechanism. It was found that 1 can induce GPCR desensitization and
      internalization, and such effects were mediated by the activation of conventional
      protein kinase C.

PMID- 22650646
TI  - Low carbohydrate diet in type 1 diabetes, long-term improvement and adherence: A
      clinical audit.
AB  - BACKGROUND: Reduction of dietary carbohydrates and corresponding insulin doses
      stabilizes and lowers mean blood glucose in individuals with type 1 diabetes
      within days. The long-term adherence for persons who have learned this technique
      is unknown. To assess adherence over 4 years in such a group the present audit
      was done retrospectively by record analysis for individuals who have attended an
      educational course. Adherence was assessed from HbA1c changes and individuals'
      own reports. FINDINGS: Altogether 48 persons with diabetes duration of 24 +/- 12
      years and HbA1c > = 6.1% (Mono-S; DCCT = 7.1%) attended the course. Mean HbA1c
      for all attendees was at start, at 3 months and 4 years 7.6% +/- 1.0%, 6.3 +/-
      0.7%, 6.9 +/- 1.0% respectively. The number of non-adherent persons was 25 (52%).
      HbA1c in this group was at start, at 3 months and 4 years: 7.5 +/-1.1%, 6.5 +/-
      0.8%, 7.4 +/- 0.9%. In the group of 23 (48%) adherent persons mean HbA1c was at
      start, at 3 months and 4 years 7.7 +/- 1.0%, 6.4 +/- 0.9%, 6.4 +/- 0.8%.
      CONCLUSION: Attending an educational course on dietary carbohydrate reduction and
      corresponding insulin reduction in type 1 diabetes gave lasting improvement.
      About half of the individuals adhered to the program after 4 years. The method
      may be useful in informed and motivated persons with type 1 diabetes. The number
      needed to treat to have lasting effect in 1 was 2.

PMID- 22650645
TI  - Role of mannose-binding lectin-2 polymorphism in the development of acute
      cellular rejection after transplantation for hepatitis C virus-induced liver
      disease.
AB  - The development of liver and graft disease is suspected to be affected by genetic
      diversity. Mannose-binding lectin-2 (MBL-2) is an important immunomodulatory
      factor that is involved in complement activation. The aim of our study was to
      elucidate the role of MBL-2 genotypes after liver transplantation (LT) for
      hepatitis C virus (HCV)-induced liver disease regarding the incidence of acute
      cellular rejection (ACR), graft inflammation, fibrosis development, and antiviral
      treatment response. METHODS: A group of 149 patients who underwent LT for HCV
      induced liver disease were genotyped for MBL-2 (rs7096206; G/C) by TaqMan
      genotyping assay. We evaluated 518 post-LT protocol biopsies and at least 98
      urgent liver biopsies regarding graft fibrosis stages, inflammation grades, and
      evidence for rejection within MBL-2 genotype groups. RESULT: No association of
      MBL-2 polymorphisms was observed regarding inflammation, fibrosis, and antiviral
      treatment outcome. However, the C allele of the MBL-2 gene (P = 0.001) and gender
      compatibility (P = 0.012) were factors significantly associated with the
      incidence of ACR. CONCLUSION: MBL-2 polymorphisms and gender are involved in the
      development of ACR after LT. CC genotype and gender match may be regarded as risk
      factors for ACR in HCV-positive graft recipients. Further studies are needed to
      confirm and verify this observation in non-HCV groups as well.

PMID- 22650647
TI  - Review article: biofilm formation by  Helicobacter pylori as a target for
      eradication of resistant infection.
AB  - BACKGROUND: Helicobacter pylori is one of the most common causes of bacterial
      infection in humans. Resistance of this infection to conventional therapies has
      suggested the role of a biofilm-growing bacterium, which is recalcitrant to many
      antimicrobial agents. AIM: To review the current knowledge on biofilm formation
      by H. pylori and to discuss the implications of this behaviour in the context of
      human infections and their treatment. RESULTS: Scanning electron microscopy
      analysis of gastric biopsies of infected patients demonstrated that H. pylori
      forms biofilm on the gastric mucosa epithelium. Adaptation to the biofilm
      environment may produce many persister cells, namely dormant cells, which are
      highly tolerant to antimicrobials that could account for the recalcitrance of H.
      pylori infections in vivo. Resistant H. pylori infection has become increasingly
      common with triple or quadruple therapy, even in the presence of H. pylori
      strains susceptible to all antibiotics. The mucolytic and thiol-containing
      antioxidant N-acetylcysteine, associated with antibiotics, was successfully used
      in clinic for therapy of patients with chronic respiratory tract infections.
      Consistently, N-acetylcysteine treatment prior to starting antibiotic therapy
      allowed the disappearance of gastric biofilm in all patients in whom H. pylori
      was eradicated. CONCLUSION: Effective strategies targeting H. pylori biofilm
      infections are possible, through the use of substances degrading components of
      the biofilm.

PMID- 22650648
TI  - Antibody-drug conjugates - a perfect synergy.
AB  - INTRODUCTION: There is a great unmet need for effective new treatments in cancer,
      which continues to be a major cause of death. Antibody-drug conjugates (ADCs) are
      emerging, after a long gestation, as a class of biopharmaceuticals with the
      potential to address this need by directing highly potent cytotoxic drugs to
      their point of action. There is increasing interest in ADCs by major
      pharmaceutical companies and a growing pipeline of candidates for clinical use.
      This review summarises progress with development of this new class of drugs.
      AREAS COVERED: The authors describe separately the antibody and drug elements of
      ADCs and then examine the technology and consequences of linkage. The work is
      presented in the light of recent developments in the design, using clinical
      examples where possible. EXPERT OPINION: Since their emergence as independent
      drugs, antibodies and chemotherapy are being brought together in effective
      synergy. The conjunction is timely: many of the technical challenges in preparing
      antibodies have been addressed; potent new drugs are available and linker
      technology is advancing apace. ADCs however are not just a sum of their
      individual parts. The current challenge is in understanding the holistic nature
      of this exciting class of drugs that promise a new avenue for cancer treatment.
      Target selection, the interaction of ADC with tumour and off-tumour targets and
      the internalisation of ADCs, are critical to the effective maturation of ADC
      technology. Ongoing recent developments in attachment sites and linker chemistry
      can provide fine-tuning of drug loading, elements of ADC PK and off-target ADC
      toxicity.

PMID- 22650758
TI  - Daisy chain assembly formed from a cucurbit[6]uril derivative.
AB  - The building block synthesis of a derivative of CB[6] that bears a reactive
      propargyloxy group and its functionalization by click chemistry to yield 1 which
      contains a covalently attached isobutylammonium group is presented. Compound 1
      undergoes self-assembly to yield a cyclic [c2] daisy chain assembly (1(2)) in
      water. The behavior of 1(2) in response to various stimuli (e.g., guests and
      CB[n] receptors) is described.

PMID- 22650759
TI  - Computerized quality assessment of phonocardiogram signal measurement-acquisition
      parameters.
AB  - The major focus of this study is to describe and develop a phonocardiogram (PCG)
      signal measurement binary quality assessment (accept-reject) technique. The
      proposed algorithm is composed of three major stages: preprocessing, numerical
      based quality measurement and advanced measurement subroutines. The preprocessing
      step includes normalization, wavelet-based threshold denoising and baseline
      wander removal. The numerical-based quality measurement routine includes two
      separate stages based on energy and level of noise of the PCG signal. The
      advanced quality measurement step is mainly based on the interval of S1 and S2
      sounds. The proposed technique was applied to 400 2-min PCG signals gathered by
      volunteers with range of skills in PCG data acquisition from patients with
      different types of valve diseases from their 2R (aortic), 2L (pulmonic), 4R
      (apex) and 4L (tricuspid) positions by implementing an electronic stethoscope (3M
      Littmann((r)) 3200, 4 kHz sampling frequency). The dataset was firstly annotated
      manually and then, by applying the proposed algorithm, an accuracy of 95.25% was
      achieved.

PMID- 22650760
TI  - Experimental and computational analysis of soft tissue mechanical response under
      negative pressure in forearm.
AB  - BACKGROUND: Instrumentation, relying on the use of negative pressure (suction),
      has been introduced to reduce pathological tissue swelling. Then, relative
      contribution of skin, adipose tissue and muscle, to the overall mechanical
      response is not known. METHODS: Under suction, stretch of soft tissues in the
      forearm of human subjects (N = 11) was experimentally measured at rest and under
      venous occlusion. Three dimensional, fibril-reinforced hyperelastic finite
      element (FE) model was constructed, the model response was matched with the
      experimental measurement and the mechanical characteristics of each tissue were
      derived. Parametric analyses were conducted to evaluate the impact of different
      tissues on the total stretch. RESULTS: The model suggested that, at large
      strains, the stretch response was more sensitive to changes in the elastic
      modulus of skin than those in adipose tissue. During venous occlusion, reduction
      of the stretch of forearm tissues was related to stiffening of the skin and
      adipose tissue, as evidenced by increased modulus of 27 +/- 21% and 35 +/- 26%,
      respectively. CONCLUSION: The method based on suction may be used to diagnose and
      monitor changes in properties of soft tissues, especially those of skin, as well
      as tissue swelling typical to pathological conditions such as oedema.

PMID- 22650762
TI  - Experiment and theory of low-pressure nitrogen adsorption in organic layers
      supported or grafted on inorganic adsorbents: toward a tool to characterize
      surfaces of hybrid organic/inorganic systems.
AB  - We report experimental nitrogen adsorption isotherms of organics-coated silicas,
      which exhibit a low-pressure desorption branch that does not meet the adsorption
      branch upon emptying of the pores. To address the physical origin of such a
      hysteresis loop, we propose an equilibrium thermodynamic model that enables one
      to explain this phenomenon. The present model assumes that, upon adsorption, a
      small amount of nitrogen molecules penetrate within the organic layer and reach
      adsorption sites that are located on the inorganic surface, between the grafted
      or adsorbed organic molecules. The number of accessible adsorption sites thus
      varies with the increasing gas pressure, and then we assume that it stays
      constant upon desorption. Comparison with experimental data shows that our model
      captures the features of nitrogen adsorption on such hybrid organic/inorganic
      materials. In particular, in addition to predicting the shape of the adsorption
      isotherm, the model is able to estimate, with a reasonable number of adjustable
      parameters, the height of the low-pressure hysteresis loop and to assess in a
      qualitative fashion the local density of the organic chains at the surface of the
      material.

PMID- 22650761
TI  - Identification of methylated proteins in the yeast small ribosomal subunit: a
      role for SPOUT methyltransferases in protein arginine methylation.
AB  - We have characterized the posttranslational methylation of Rps2, Rps3, and
      Rps27a, three small ribosomal subunit proteins in the yeast Saccharomyces
      cerevisiae, using mass spectrometry and amino acid analysis. We found that Rps2
      is substoichiometrically modified at arginine-10 by the Rmt1 methyltransferase.
      We demonstrated that Rps3 is stoichiometrically modified by omega-monomethylation
      at arginine-146 by mass spectrometric and site-directed mutagenic analyses.
      Substitution of alanine for arginine at position 146 is associated with slow cell
      growth, suggesting that the amino acid identity at this site may influence
      ribosomal function and/or biogenesis. Analysis of the three-dimensional structure
      of Rps3 in S. cerevisiae shows that arginine-146 makes contacts with the small
      subunit rRNA. Screening of deletion mutants encoding potential yeast
      methyltransferases revealed that the loss of the YOR021C gene results in the
      absence of methylation of Rps3. We demonstrated that recombinant Yor021c
      catalyzes omega-monomethylarginine formation when incubated with S
      adenosylmethionine and hypomethylated ribosomes prepared from a YOR021C deletion
      strain. Interestingly, Yor021c belongs to the family of SPOUT methyltransferases
      that, to date, have only been shown to modify RNA substrates. Our findings
      suggest a wider role for SPOUT methyltransferases in nature. Finally, we have
      demonstrated the presence of a stoichiometrically methylated cysteine residue at
      position 39 of Rps27a in a zinc-cysteine cluster. The discovery of these three
      novel sites of protein modification within the small ribosomal subunit will now
      allow for an analysis of their functional roles in translation and possibly other
      cellular processes.

PMID- 22650763
TI  - How media campaigns influence children's physical activity: expanding the
      normative mechanisms of the theory of planned behavior.
AB  - This study explicates mechanisms of media campaign effectiveness in the context
      of children's physical activity. The authors' model expands the theory of planned
      behavior by integrating injunctive and descriptive norms into its normative
      mechanism. Analysis of a 3-wave nationally representative evaluation survey among
      1,623 tweens indicates that campaign exposure is significantly related, but only
      indirectly, to both physical activity intention and physical activity behavior.
      Instead, campaign exposure seems more strongly related to perceived behavioral
      control and attitudes toward physical activity. By contrast, perceived behavioral
      control and descriptive norms are strongly related to behavioral intention. The
      findings suggest that integrating normative mechanisms with the theory of planned
      behavior can improve efforts to predict and explain a health behavior.

PMID- 22650765
TI  - Distinguishing nanowire and nanotube formation by the deposition current
      transients.
AB  - High aspect ratio Ni nanowires (NWs) and nanotubes (NTs) were electrodeposited
      inside ordered arrays of self-assembled pores (approximately 50 nm in diameter
      and approximately 50 MUm in length) in anodic alumina templates by a
      potentiostatic method. The current transients monitored during each process
      allowed us to distinguish between NW and NT formation. The depositions were long
      enough for the deposited metal to reach the top of the template and form a
      continuous Ni film. The overfilling process was found to occur in two steps when
      depositing NWs and in a single step in the case of NTs. A comparative study of
      the morphological, structural, and magnetic properties of the Ni NWs and NTs was
      performed using scanning electron microscopy, X-ray diffraction, and vibrating
      sample magnetometry, respectively.

PMID- 22650766
TI  - The International Health Partnership Plus: rhetoric or real change? Results of a
      self-reported survey in the context of the 4th High Level Forum on Aid
      Effectiveness in Busan.
AB  - BACKGROUND: The Paris Declaration on Aid Effectiveness, which provides an
      international agreement on how to deliver aid, has recently been reviewed by the
      Organization for Economic Co-operation and Development (OECD). Health sector aid
      effectiveness is important, given the volume of financial aid and the number of
      mechanisms through which health assistance is provided. Recognizing this, the
      international community created the International Health Partnership (IHP+), to
      apply the Paris Declaration to the health sector. This paper, which presents
      findings from an independent monitoring process (IHP+Results), makes a valuable
      contribution to the literature in the context of the recent 4th High Level Forum
      on Aid Effectiveness in Busan, Korea. METHODS: IHP+Results monitored commitments
      made under the IHP + using an agreed framework with twelve measures for IHP +
      Development Partners and ten for IHP + recipient country governments. Data were
      collected through self-administered survey tools. IHP+Results analyzed these
      data, using transparent criteria, to produce Scorecards as a means to highlight
      progress against commitments and thereby strengthen mutual accountability amongst
      IHP + signatories. RESULTS: There have been incremental improvements in the
      strengthening of national planning processes and principles around mutual
      accountability. There has also been progress in Development Partners aligning
      their support with national budgets. But there is a lack of progress in the use
      of countries' financial management and procurement systems, and in the
      integration of duplicative performance reporting frameworks and information
      systems. DISCUSSION AND CONCLUSIONS: External, independent monitoring is
      potentially useful for strengthening accountability in health sector aid. While
      progress in strengthening country ownership, harmonisation and alignment seems
      evident, there are ongoing challenges. In spite of some useful findings, there
      are limitations with IHP + monitoring that need to be addressed. This is not
      surprising given the challenge of rigorously monitoring Development Partners
      across multiple recipient countries within complex global systems. The findings
      presented here suggest that the health sector is ahead of the game--in terms of
      having an established mechanism to promote alignment and harmonisation, and a
      relatively advanced monitoring framework and methods. But to capitalise on this,
      IHP + signatories should: a) reaffirm their commitments to the IHP+; b) actively
      embrace and participate in monitoring and evaluation processes; and c) strengthen
      in-country capacity notably amongst civil society organizations.

PMID- 22650767
TI  - 'Decision support system (DSS) for prevention of cardiovascular disease (CVD)
      among hypertensive (HTN) patients in Andhra Pradesh, India'--a cluster randomised
      community intervention trial.
AB  - BACKGROUND: Very few studies having decision support systems as an intervention
      report on patient outcomes for cardiovascular disease in the Western world. The
      potential role of decision support system for the management of blood pressure
      among Indian hypertensives remains unclear. We propose a cluster randomised trial
      that aims to test the effectiveness and cost effectiveness of DSS among Indian
      hypertensive patients. METHODS: The trial design is a cluster randomised
      community intervention trial, in which the participants would be adult male and
      female hypertensive patients, in the age group of 35 to 64 years, reporting to
      the Primary Health Care centres of Mahabubnagar district, Andhra Pradesh, India.
      The objective of the study is to test the effectiveness and compare the cost
      effectiveness and cost utility among hypertensive subjects randomized to receive
      either decision support system or a chart based algorithmic support system in
      urban and rural areas of a district in the state of Andhra Pradesh, India
      (baseline versus 12 months follow up). The primary outcome would be a comparison
      of the systolic blood pressure at 0 and 12 months among hypertensive patients
      randomized to receive the decision support system or the chart based algorithmic
      support system. Computer generated randomisation and an investigator and analyser
      blinded method would be followed. 1600 participants; 800 to each arm; each arm
      having eight clusters of hundred participants each have been recruited between 01
      August 2011 - 01 March 2012. A twelve month follow up will be completed by March
      2013 and results are expected by April 2013. DISCUSSION: This cluster randomized
      community intervention trial on DSS will enable policy makers to find out the
      effectiveness, cost effectiveness and cost utility of decision support system for
      management of blood pressure among hypertensive patients in India. Most of the
      previous studies on decision support system have focused on physician
      performance, adherence and on preventive care reminders. The uniqueness of the
      proposed study lies in finding out the effectiveness of a decision support system
      on patient related outcomes. TRIAL REGISTRATION: CTRI/2012/03/002476, Clinical
      Trial Registry - India.

PMID- 22650795
TI  - Radioligand dissociation measurements: potential interference of rebinding and
      allosteric mechanisms and physiological relevance of the biological model
      systems.
AB  - INTRODUCTION: In many situations, optimal drug therapy requires continuing high
      levels of target occupancy and this notion has led pharmacologists to focus their
      attention on the rate by which drug candidates dissociate from their target. To
      this end, radioligand dissociation experiments are often carried out on in vitro
      models, such as intact cells and the membranes thereof, but the interpretation of
      the collected data is sometimes ambiguous. AREAS COVERED: Pharmacodynamics is
      concerned about what the drug does to the target and, in this respect, allosteric
      modulation constitutes a quite novel, very promising research topic. The ability
      of unlabeled drugs to accelerate radioligand dissociation is often advocated to
      be a hallmark of such mechanism. Yet, the present computerized simulations reveal
      that competitive drugs produce the same effect by preventing hindered diffusion-
      and "forced proximity"-related rebinding of the radioligand. Herein, the authors
      provide hints to discern among those mechanisms. EXPERT OPINION: A critical, but
      constructive appraisal of radioligand dissociation binding data leads to the
      viewpoint that, from a physiological perspective, dissociation from confluent
      target-expressing plated cells, when in a naive medium, is likely to provide the
      most pertinent insight in that ligand's in vivo residence time.

PMID- 22650764
TI  - Pleistocene speciation with and without gene flow in Euphaea damselflies of
      subtropical and tropical East Asian islands.
AB  - Climatic oscillations during the Pleistocene period could have had a profound
      impact on the origin of tropical species by the alternation of allopatric
      isolation and interpopulation gene flow cycles. However, whether tropical
      speciation involves strictly allopatric isolation, or proceeds in the face of
      homogenizing gene flow, is relatively unclear. Here, we investigated geographical
      modes of speciation in four closely related Euphaea damselfly species endemic to
      the subtropical and tropical East Asian islands using coalescent analyses of a
      multilocus data set. The reconstructed phylogenies demonstrated distinct species
      status for each of the four species and the existence of two sister species
      pairs, Euphaea formosa/E. yayeyamana and E. decorata/E. ornata. The species
      divergence time of the sibling Euphaea damselflies dates back to within the last
      one Mya of the Middle to Lower Pleistocene. The speciation between the populous
      E. formosa of Taiwan and the less numerous E. yayeyamana of the Yaeyama islands
      occurred despite significant bidirectional, asymmetric gene flow, which is
      strongly inconsistent with a strictly allopatric model. In contrast, speciation
      of the approximately equal-sized populations of E. decorata of the southeast
      Asian mainland and E. ornata of Hainan is inferred to have involved allopatric
      divergence without gene flow. Our findings suggest that differential selection of
      natural or sexual environments is a prominent driver of species divergence in
      subtropical E. formosa and E. yayeyamana; whereas for tropical E. decorata and E.
      ornata at lower latitudes, allopatric isolation may well be a pivotal promoter of
      species formation.

PMID- 22650796
TI  - Anti-atherogenic effect of chromium picolinate in streptozotocin-induced
      experimental diabetes.
AB  - BACKGROUND: Several studies have implicated changes in the levels of trace
      elements in diabetes. Chromium is one such element that seems to potentiate
      insulin action, thereby regulating carbohydrate and lipid metabolism. The aim of
      the present study was to evaluate the effect of chromium supplementation as
      chromium picolinate on the lipid profile of streptozotocin (STZ)-induced diabetic
      rats. METHODS: Rats were rendered diabetic by a single injection of STZ (50
      mg/kg, i.p.). Chromium picolinate (1 mg/kg per day, p.o.) was administered to
      rats for a period of 4 weeks. At the end of the treatment period, plasma total
      lipids, triglycerides, total cholesterol and lipoprotein levels were determined,
      as was hepatic glucose-6-phosphate dehydrogenase activity. RESULTS: Total plasma
      lipids increased significantly in diabetic rats and this increase was ameliorated
      by chromium treatment for 4 weeks. Elevated total lipids in diabetic rats were
      due to increased plasma triglyceride and cholesterol levels. Chromium
      supplementation lowered plasma triglyceride and cholesterol levels to near
      normal. Chromium treatment also normalized low-density lipoprotein-cholesterol
      (LDL-C) and very low-density lipoprotein-cholesterol levels and improved the
      total cholesterol:high-density lipoprotein-cholesterol (HDL-C) and HDL-C:LDL-C
      ratios, suggesting an anti-atherogenic effect. In addition to improving the
      plasma lipid profile, chromium supplementation normalized liver glucose-6
      phosphate dehydrogenase activity in diabetic rats. CONCLUSIONS: These results
      provide evidence that chromium picolinate effectively attenuates the dyslipidemia
      associated with diabetes and thus can be used as an adjuvant therapy in the
      treatment of diabetes and its associated complications.

PMID- 22650797
TI  - On the learnability of frequent and infrequent word orders: an artificial
      language learning study.
AB  - Most languages have a basic or "canonical" word order, which determines the
      relative positions of the subject (S), the verb (V), and the object (O) in a
      typical declarative sentence. The frequency of occurrence of the six possible
      word orders among world languages is not distributed uniformly. While SVO and SOV
      represent around 85% of world languages, orders like VSO (9%) or OSV (0.5%) are
      much less frequent or extremely rare. One possible explanation for this asymmetry
      is that biological and cognitive constraints for structured sequence processing
      make some word orders easier to be processed than others. Therefore, the high
      frequency of these word orders would be related to their higher learnability. The
      aim of the present study was to compare the learnability of different word orders
      between groups of adult subjects. Four artificial languages with different word
      orders were trained: two frequent (SVO, SOV) and two infrequent (VSO, OSV). In a
      test stage, subjects were asked to discriminate between new correct sentences and
      syntax or semantic violations. Higher performance rates and faster responses were
      observed for more frequent word orders. The results support the hypothesis that
      more frequent word orders are more easily learned.

PMID- 22650798
TI  - Short communication: broader T cell responses directed against human
      immunodeficiency virus type 1 in infected Chinese individuals through blood-borne
      transmission in comparison with mucosal transmission.
AB  - Cellular immune responses play a critical role in the control of human
      immunodeficiency virus type 1 (HIV-1), but less is known about the impact of
      transmission routes on immune defenses against HIV-1. Here, we report that
      subjects infected with HIV-1 through contaminated blood showed stronger HIV
      specific T cell responses than those infected through mucosa, both in breadth
      (6.9+/-2.5 vs. 2.3+/-0.5, p=0.0293) and in magnitude [1270.0+/-544.9 vs. 409.5+/
      121.3 SFU per million peripheral blood mononuclear cells (PBMCs), p=0.0223], by
      using a matrix of 404 overlapping peptides spanning all expressed HIV-1 proteins
      in an interferon (IFN)-gamma enzyme-linked immunospot (ELISpot) assay. Our
      observation indicates that different mechanisms might be involved in the
      priming/generating of anti-HIV-specific T cell responses through different
      transmission routes.

PMID- 22650799
TI  - Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in healthy
      Korean subjects.
AB  - WHAT IS KNOWN AND OBJECTIVE: Dexmedetomidine is a selective alpha2-adrenoreceptor
      agonist used for sedation in critically ill patients. The current study aimed to
      evaluate the pharmacokinetics (PKs), pharmacodynamics and tolerability of
      intravenous dexmedetomidine in healthy Korean subjects. METHODS: A randomized,
      double-blind, placebo-controlled study with three parallel dosage groups was
      conducted. Twenty-four subjects were randomly assigned to placebo or one of three
      dexmedetomidine dosing regimens, 3 MUg/kg/h for 10 min followed by 0.17 MUg/kg/h
      for 50 min (low dose), 6 MUg/kg/h for 10 min followed by 0.34 MUg/kg/h for 50 min
      (middle dose) and 3.7 MUg/kg/h for 35 min followed by 0.7 MUg/kg/h for 25 min
      (high dose). Serial blood samples for PK analysis were taken up to 12 h. PK
      parameters were determined using non-compartmental methods (WinNonlin((r))), and
      a population PK model was developed using nonmem((r)). The sedative effect of
      dexmedetomidine was assessed by Ramsay sedation score and visual analogue
      scales/sedation. Adverse events, clinical laboratory tests, electrocardiograms,
      physical examinations and vital signs were monitored for tolerability assessment.
      RESULTS: Six subjects were assigned to each of the three active treatment group
      or placebo group. The AUC(last) of the low-, middle- and high-dose group were
      1096.8 +/- 119.9 (mean +/- SD) ng*h/L, 2643.0 +/- 353.2 ng*h/L and 5600.6 +/-
      411.0 ng*h/L, respectively. PK of dexmedetomidine was best described using a two
      compartment model. The typical value of the population model can be calculated
      using the following equations: central volume of distribution (L) = 19.9
      (age/27)(0.954), peripheral volume of distribution (L) = 59.4, clearance (L/h) =
      33.7 (albumin level/4.3)(1.42) and inter-compartment clearance (L/h) = 67.7.
      Sedative effects were significantly increased by dexmedetomidine compared to
      placebo. The blood pressure and heart rate were decreased, but oxygen saturation
      was maintained stable. WHAT IS NEW AND CONCLUSION: Dexmedetomidine shows linear
      PK characteristics and dose-dependent sedative effects. A two-compartment
      population PK model was developed for healthy Korean subjects. The PK parameter
      estimates are similar in Koreans and Caucasians.

PMID- 22650801
TI  - Kinetic resolution of amines via dual catalysis: remarkable dependence of
      selectivity on the achiral cocatalyst.
AB  - A dual-catalysis/anion-binding approach with a chiral hydrogen bonding (HB)
      catalyst and an achiral nucleophilic cocatalyst was applied to the kinetic
      resolution of amines. Out of a structurally diverse collection of 22 nucleophilic
      species, 4-di-n-propylaminopyridine emerged as the most efficient cocatalyst,
      allowing for the kinetic resolution of benzylic amines with s-factors of up to
      67.

PMID- 22650800
TI  - Metabolic syndrome among Sri Lankan adults: prevalence, patterns and correlates.
AB  - Metabolic Syndrome (MS) increases the risk for Coronary Artery Disease, stroke
      and diabetes. MS is twice more common amongst South Asian immigrants in US
      compared to native Caucasians. There are no nationally representative studies on
      prevalence of MS from any of the South Asian countries. The present study aims to
      evaluate the prevalence of MS among Sri Lankan adults and investigates its
      relationships with socio-demographic, clinical and biochemical parameters. Data
      on MS and its associated details were obtained from a population-based cross
      sectional study conducted between years 2005-2006. MS was defined according to
      the International Diabetes Federation criteria. A binary logistic regression
      analysis was performed using the dichotomous variable MS (0 = absent, 1 =
      present). The independent co-variants were: gender, age category, area of
      residence, ethnicity, level of education, income and physical activity. Sample
      size was 4,485 (Response rate-89.7%), 39.5% were males and mean age was 46.1 +/-
      15.1 years. The crude prevalence of MS was 27.1% (95% CI: 25.8-28.5), and age
      adjusted prevalence was 24.3% (95% CI: 23.0-25.6). Prevalence in males and
      females were 18.4% (95% CI: 16.5-20.3) and 28.3% (95% CI: 26.6-30.0) respectively
      (p < 0.001). Urban adults (34.8% [95% CI: 31.8-37.9]) had a significantly higher
      prevalence than rural adults (21.6% [95% CI: 20.2-23.0]). Among ethnic groups,
      the highest prevalence of MS was observed in Sri Lankan Moors (43.0% [95% CI:
      37.2-48.9]). In all adults, MS was observed in those with the highest level of
      education and monthly household income. Prevalence of MS in the different
      physical activity categories of the IPAQ were; 'inactive'-38.8% (95% CI 34.5
      43.2), 'moderately active'-33.5% (95% CI 30.9-36.1) and 'active'-21.1% (95% CI
      19.6-22.7). The results of the binary logistic regression analysis indicates that
      female gender (OR:1.7), increasing age, urban living (OR:1.7), Moor ethnicity
      (OR:2.6), secondary (OR:1.5) and tertiary levels of education (OR:2.3), monthly
      household income LKR 7,000-24,999 (OR:1.5) and >50,000 (OR:2.1), and physical
      inactivity (OR:1.6), all significantly increased risk of developing MS. MS is
      common among Sri Lankan adults affecting nearly one-fourth of the population.
      Female gender, increasing age, urban living, higher socio-economical status and
      physical inactivity were important associated factors.

PMID- 22650802
TI  - Medroxyprogesterone acetate for refractory emesis in cisplatin-treated patients.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing
      side effects in systemic chemotherapies. Recently, several effective agents have
      been developed to prevent CINV, and CINV can be prevented in 70%-80% of patients
      receiving chemotherapies. Conversely, 20%-30% of patients still suffer from CINV
      despite recommended optimal antiemetic preventions. Refractory emesis is defined
      as emesis occuring despite the use of antiemetic prophylaxis during the previous
      cycle of chemotherapy. Salvage treatments for refractory emesis are necessary,
      but there are few effective treatments at present. We consider
      medroxyprogesterone acetate to be a potentially promising agent for refractory
      emesis. We encountered three cases in which medroxyprogesterone acetate was
      extremely effective for refractory emesis induced by cisplatin-containing
      chemotherapy.

PMID- 22650804
TI  - Langmuir. Biographical sketches.

PMID- 22650803
TI  - Rapid acute onset of bronchiolitis obliterans syndrome in a lung transplant
      recipient after respiratory syncytial virus infection.
AB  - Bronchiolitis obliterans syndrome (BOS) can have either an acute or chronic onset
      with an abrupt or insidious course. The diagnosis is typically achieved by
      physiological criteria with development of a sustained decline in expiratory flow
      rates for at least 3 weeks. We review the rapid development of acute BOS and
      bronchiectasis after respiratory syncytial virus infection in a lung transplant
      recipient, who had been doing well with normal pulmonary function for 3 years
      after lung transplantation.

PMID- 22650805
TI  - Strong preferences of dopamine and l-dopa towards lipid head group: importance of
      lipid composition and implication for neurotransmitter metabolism.
AB  - The interactions of the neurotransmitter dopamine, and its precursor l-dopa, with
      membrane lipids were investigated through a set of molecular dynamic simulations
      with all atom resolution. The results obtained indicate that both dopamine and l
      dopa have a pronounced association with the lipid head groups, predominantly
      mediated through H-bonds. As a result the molecules are anchored to the
      interfacial region of the membrane. The strength of this interaction is dependent
      on lipid composition - the presence of phosphatidylserine leads to an increase in
      the strength of this interaction, resulting in an H-bond network with a lifetime
      much longer than the timescale of our simulations. Also, bilayers that include
      sphingomieline and cholesterol interact strongly with dopamine and l-dopa. We
      postulate that the high membrane association that we have observed for both
      dopamine and l-dopa could have the following effects: 1) when on the plasma
      membrane exterior, favour the availability of these compounds for cell membrane
      uptake processes and, 2) when on an internal membrane surface, accentuate the
      importance of membrane-bound metabolizing enzymes over their soluble
      counterparts.

PMID- 22650906
TI  - Hybrid transparent electrodes of silver nanowires and carbon nanotubes: a low
      temperature solution process.
AB  - Hybrid transparent electrodes with silver nanowires (AgNWs) and single-walled
      carbon nanotubes (SWCNTs) were fabricated on plastic films by a low-temperature
      solution process. The hybrid transparent electrodes exhibited a sheet resistance
      of 29.2 Omega/sq with a transparency of 80% when 6 wt.% of SWCNTs was mixed with
      AgNWs. This sheet resistance was less than one-fourth that of the AgNW
      transparent electrodes that were prepared using the same method. This reduction
      in sheet resistance is because the SWCNTs formed bridges between the AgNWs, thus,
      resulting in high conductivity of the hybrid transparent electrodes. The hybrid
      electrodes formed on plastic films exhibited high conductivity as well as
      excellent stability in sheet resistance when tested using a repeated bending
      test.PACS: 62.23.Hj; 61.48.De; 81.15.-z.

PMID- 22650907
TI  - Tailored jeffamine molecular tools for ordering mesoporous silica.
AB  - Herein, we report the formation of organized mesoporous silica materials prepared
      from a novel nonionic gemini surfactant, myristoyl-end-capped Jeffamine,
      synthesized from a polyoxyalkyleneamine (ED900). The behavior of the modified
      Jeffamine in water was first investigated. A direct micellar phase (L(1)) and a
      hexagonal (H(1)) liquid crystal were found. The structure of the micelles was
      investigated from the SAXS and the analysis by generalized indirect Fourier
      transformation, which show that the particles are globular of core-shell type.
      The myristoyl chains, located at the ends of the amphiphile molecule, are
      assembled to form the core of the micelles and, as a consequence, the molecules
      are folded over on themselves. Mesoporous materials were then synthesized from
      the self-assembly mechanism. The recovered materials were characterized by SAXS
      measurements, nitrogen adsorption-desorption analysis, and transmission and
      scanning electron microscopy. The results clearly evidence that by modifying the
      synthesis parameters, such as the surfactant/silica precursor molar ratio and the
      hydrothermal conditions, one can control the size and the nanostructuring of the
      resulting material. It was observed that, the lower the temperature of the
      hydrothermal treatment, the better the mesopore ordering.

PMID- 22650962
TI  - Sensitivity changes over the course of infection increases the likelihood of
      resistance against fusion but not CCR5 receptor blockers.
AB  - As HIV-1 evolves over the course of infection, resistance against antiretrovirals
      may arise in the absence of drug pressure, especially against receptor and fusion
      blockers because of the extensive changes observed in the envelope glycoprotein.
      Here we show that viruses from the chronic phase of disease are significantly
      less sensitive to CCR5 receptor and fusion blockers compared to early infection
      variants. Differences in susceptibility to CCR5 antagonists were observed in
      spite of no demonstrable CXCR4 receptor utilization. No significant sensitivity
      differences were observed to another entry blocker, soluble CD4, or to reverse
      transcriptase, protease, or integrase inhibitors. Chronic as compared to early
      phase variants demonstrated greater replication when passaged in the presence of
      subinhibitory concentrations of fusion but not CCR5 receptor inhibitors. Fusion
      antagonist resistance, however, emerged from only one chronic phase virus
      culture. Because sensitivity to receptor and fusion antagonists is correlated
      with receptor affinity and fusion capacity, respectively, changes that occur in
      the envelope glycoprotein over the course of infection confer greater ability to
      use the CCR5 receptor and increased fusion ability. Our in vitro passage studies
      suggest that these evolving phenotypes increase the likelihood of resistance
      against fusion but not CCR5 receptor blockers.

PMID- 22650963
TI  - The Skp chaperone helps fold soluble proteins in vitro by inhibiting aggregation.
AB  - The periplasmic seventeen kilodalton protein (Skp) chaperone has been
      characterized primarily for its role in outer membrane protein (OMP) biogenesis,
      during which the jellyfish-like trimeric protein encapsulates partially folded
      OMPs, protecting them from the aqueous environment until delivery to the BAM
      outer membrane protein insertion complex. However, Skp is increasingly recognized
      as a chaperone that also assists in folding soluble proteins in the bacterial
      periplasm. In this capacity, Skp coexpression increases the active yields of many
      recombinant proteins and bacterial virulence factors. Using a panel of single
      chain antibodies and a single-chain T-cell receptor (collectively termed scFvs)
      possessing varying stabilities and biophysical characteristics, we performed in
      vivo expression and in vitro folding and aggregation assays in the presence or
      absence of Skp. For Skp-sensitive scFvs, the presence of Skp during in vitro
      refolding assays reduced aggregation but did not alter the observed folding
      rates, resulting in a higher overall yield of active protein. Of the proteins
      analyzed, Skp sensitivity in all assays correlated with the presence of folding
      intermediates, as observed with urea denaturation studies. These results are
      consistent with Skp acting as a holdase, sequestering partially folded
      intermediates and thereby preventing aggregation. Because not all soluble
      proteins are sensitive to Skp coexpression, we hypothesize that the presence of a
      long-lived protein folding intermediate renders a protein sensitive to Skp.
      Improved understanding of the bacterial periplasmic protein folding machinery may
      assist in high-level recombinant protein expression and may help identify novel
      approaches to block bacterial virulence.

PMID- 22650966
TI  - Editorial: Pharmacotherapies for the treatment of alcohol abuse and dependence.

PMID- 22650967
TI  - The effect of intensity on relative pitch.
AB  - In two experiments, we examined the effect of intensity and intensity change on
      judgements of pitch differences or interval size. In Experiment 1, 39 musically
      untrained participants rated the size of the interval spanned by two pitches
      within individual gliding tones. Tones were presented at high intensity, low
      intensity, looming intensity (up-ramp), and fading intensity (down-ramp) and
      glided between two pitches spanning either 6 or 7 semitones (a tritone or a
      perfect fifth interval). The pitch shift occurred in either ascending or
      descending directions. Experiment 2 repeated the conditions of Experiment 1 but
      the shifts in pitch and intensity occurred across two discrete tones (i.e., a
      melodic interval). Results indicated that participants were sensitive to the
      differences in interval size presented: Ratings were significantly higher when
      two pitches differed by 7 semitones than when they differed by 6 semitones.
      However, ratings were also dependent on whether the interval was high or low in
      intensity, whether it increased or decreased in intensity across the two pitches,
      and whether the interval was ascending or descending in pitch. Such influences
      illustrate that the perception of pitch relations does not always adhere to a
      logarithmic function as implied by their musical labels, but that identical
      intervals are perceived as substantially different in size depending on other
      attributes of the sound source.

PMID- 22650968
TI  - Polyelectrolyte-surfactant complex as a template for the synthesis of zeolites
      with intracrystalline mesopores.
AB  - Mesoporous zeolite silicalite-1 and Al-ZSM-5 with intracrystalline mesopores were
      synthesized with polyelectrolyte-surfactant complex as the template. Complex
      colloids were first formed by self-assembly of the anionic polymer poly(acrylic
      acid) (PAA) and the cationic surfactant cetyltrimethylammonium bromide (CTAB) in
      basic solution. During the synthesis procedure, upon the addition of the silica
      source, microporous template (tetrapropylammonium hydroxide), and NaCl, these
      PAA/CTA complex colloids underwent dissociation and gave rise to the formation of
      hollow silica spheres with mesoporous shells templated by CTAB micelles and PAA
      domains as the core. Under hydrothermal treatment, the hollow silica spheres
      gradually merged together to form larger particles with the PAA domains embedded
      as the space occupant, which acted as a template for intracrystalline mesopores
      during the crystallization of the zeolite framework. Amphiphilic organosilane was
      used to enhance the connection between the PAA domain and the silica phase during
      the synthesis. After calcination, single crystal-like zeolite particles with
      intracrystalline mesopores of about 5-20 nm were obtained, as characterized by X
      ray diffraction, scanning electron microscopy, transmission electron microscopy,
      and N(2) adsorption measurements. With the addition of an aluminum source in the
      synthesis, mesoporous zeolite Al-ZSM-5 with intracrystalline mesopores was also
      synthesized, and enhanced catalytic property was observed with mesoporous Al-ZSM
      5 in acetalization of cyclohexanone with methanol.

PMID- 22650973
TI  - Intramolecular condensation via an o-quinone methide: total synthesis of (+/-)
      heliol.
AB  - An acid-catalyzed intramolecular [4 + 2] cycloaddition of a non-natural
      bisabolene is reported. The key cyclocondensation was developed to access cyclic
      sesquiterpenes from linear phenolic precursors by generating a reactive o-quinone
      methide intermediate to initiate a cascade reaction. The new method was applied
      to the first total synthesis of (+/-)-heliol.

PMID- 22650965
TI  - Paradox of schizophrenia genetics: is a paradigm shift occurring?
AB  - BACKGROUND: Genetic research of schizophrenia (SCZ) based on the nuclear genome
      model (NGM) has been one of the most active areas in psychiatry for the past two
      decades. Although this effort is ongoing, the current situation of the molecular
      genetics of SCZ seems disappointing or rather perplexing. Furthermore, a
      prominent discrepancy between persistence of the disease at a relatively high
      prevalence and a low reproductive fitness of patients creates a paradox.
      Heterozygote advantage works to sustain the frequency of a putative
      susceptibility gene in the mitochondrial genome model (MGM) but not in the NGM.
      METHODS: We deduced a criterion that every nuclear susceptibility gene for SCZ
      should fulfill for the persistence of the disease under general assumptions of
      the multifactorial threshold model. SCZ-associated variants listed in the top 45
      in the SZGene Database (the version of the 23rd December, 2011) were selected,
      and the distribution of the genes that could meet or do not meet the criterion
      was surveyed. RESULTS: 19 SCZ-associated variants that do not meet the criterion
      are located outside the regions where the SCZ-associated variants that could meet
      the criterion are located. Since a SCZ-associated variant that does not meet the
      criterion cannot be a susceptibility gene, but instead must be a protective gene,
      it should be linked to a susceptibility gene in the NGM, which is contrary to
      these results. On the other hand, every protective gene on any chromosome can be
      associated with SCZ in the MGM. Based on the MGM we propose a new hypothesis that
      assumes brain-specific antioxidant defenses in which trans-synaptic activations
      of dopamine- and N-methyl-d-aspartate-receptors are involved. Most of the ten
      predictions of this hypothesis seem to accord with the major epidemiological
      facts and the results of association studies to date. CONCLUSION: The central
      paradox of SCZ genetics and the results of association studies to date argue
      against the NGM, and in its place the MGM is emerging as a viable option to
      account for genomic and pathophysiological research findings involving SCZ.

PMID- 22650974
TI  - Prevalence of dry methods in granite countertop fabrication in Oklahoma.
AB  - Granite countertop fabricators are at risk of exposure to respirable crystalline
      silica, which may cause silicosis and other lung conditions. The purpose of this
      study was to estimate the prevalence of exposure control methods, especially wet
      methods, in granite countertop fabrication in Oklahoma to assess how many workers
      might be at risk of overexposure to crystalline silica in this industry. Granite
      fabrication shops in the three largest metropolitan areas in Oklahoma were
      enumerated, and 47 of the 52 shops participated in a survey on fabrication
      methods. Countertop shops were small businesses with average work forces of fewer
      than 10 employees. Ten shops (21%) reported using exclusively wet methods during
      all fabrication steps. Thirty-five shops (74%) employing a total of about 200
      workers reported using dry methods all or most of the time in at least one
      fabrication step. The tasks most often performed dry were edge profiling (17% of
      shops), cutting of grooves for reinforcing rods (62% of shops), and cutting of
      sink openings (45% of shops). All shops reported providing either half-face or
      full-face respirators for use during fabrication, but none reported doing
      respirator fit testing. Few shops reported using any kind of dust collection
      system. These findings suggest that current consumer demand for granite
      countertops is giving rise to a new wave of workers at risk of silicosis due to
      potential overexposure to granite dust.

PMID- 22650975
TI  - Magnetic resonance imaging in patients with implanted devices.
AB  - Techniques and Technology. The use of magnetic resonance (MR) imaging as a
      diagnostic technique is rapidly expanding. In parallel, the number of patients
      with cardiac devices is constantly growing and many of them may be referred for
      MR examinations. However, implantable cardiac devices are subject to multiple
      effects from MR, and numerous safety issues need to be considered prior to
      scanning. In this review, we will summarize our experience with MR imaging of
      patients with implantable cardiac devices, and outline our safety protocol. (J
      Cardiovasc Electrophysiol, Vol. 23, pp. 1040-1042, September 2012).

PMID- 22650964
TI  - Oral versus intramuscular administration of vitamin B12 for the treatment of
      patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non
      inferiority clinical trial undertaken in the primary healthcare setting (Project
      OB12).
AB  - BACKGROUND: The oral administration of vitamin B12 offers a potentially simpler
      and cheaper alternative to parenteral administration, but its effectiveness has
      not been definitively demonstrated. The following protocol was designed to
      compare the effectiveness of orally and intramuscularly administered vitamin B12
      in the treatment of patients >=65 years of age with vitamin B12 deficiency.
      METHODS/DESIGN: The proposed study involves a controlled, randomised,
      multicentre, parallel, non-inferiority clinical trial lasting one year, involving
      23 primary healthcare centres in the Madrid region (Spain), and patients >=65
      years of age. The minimum number of patients required for the study was
      calculated as 320 (160 in each arm). Bearing in mind an estimated 8-10%
      prevalence of vitamin B12 deficiency among the population of this age group, an
      initial sample of 3556 patients will need to be recruited. Eligible patients will
      be randomly assigned to one of the two treatment arms. In the intramuscular
      treatment arm, vitamin B12 will be administered as follows: 1 mg on alternate
      days in weeks 1 and 2, 1 mg/week in weeks 3-8,and 1 mg/month in weeks 9-52. In
      the oral arm, the vitamin will be administered as: 1 mg/day in weeks 1-8 and 1
      mg/week in weeks 9-52. The main outcome variable to be monitored in both
      treatment arms is the normalisation of the serum vitamin B12 concentration at
      weeks 8, 26 and 52; the secondary outcome variables include the serum
      concentration of vitamin B12 (in pg/ml), adherence to treatment, quality of life
      (EuroQoL-5D questionnaire), patient 3satisfaction and patient preferences. All
      statistical tests will be performed with intention to treat and per protocol.
      Logistic regression with random effects will be used to adjust for prognostic
      factors. Confounding factors or factors that might alter the effect recorded will
      be taken into account in analyses. DISCUSSION: The results of this study should
      help establish, taking quality of life into account, whether the oral
      administration of vitamin B12 is an effective alternative to its intramuscular
      administration. If this administration route is effective, it should provide a
      cheaper means of treating vitamin B12 deficiency while inducing fewer adverse
      effects. Having such an alternative would also allow patient preferences to be
      taken into consideration at the time of prescribing treatment. TRIAL
      REGISTRATION: This trial has been registered with ClinicalTrials.gov, number NCT
      01476007, and under EUDRACT number 2010-024129-20.

PMID- 22650976
TI  - BindingDB and ChEMBL: online compound databases for drug discovery.
AB  - Public domain repositories of compound structures and activity data are
      indispensable tools for many aspects of pharmaceutical research, especially in
      academic environments. Such databases provide essential resources for structure
      activity data mining and the evaluation of chemoinformatics and drug design
      methods. They are also important to support scientific interactions between
      commercial and academic environments. This editorial highlights two major public
      domain compound data repositories, BindingDB and ChEMBL, which have different
      origins. BindingDB has evolved in an academic setting (and continues to be
      developed there) and ChEMBL in a biotechnology environment. The ChEMBL database
      is now maintained and further developed at the European Bioinformatics Institute
      Outstation of the European Molecular Biology Laboratory. These databases mostly
      contain structures and activity data taken from the scientific literature,
      covering different stages of compound exploration and optimization efforts, and
      provide a substantial body of complementary compound activity information.
      Together with PubChem bioassays, ChEMBL and BindingDB provide the foundation of
      compound data analysis in the public domain.

PMID- 22650977
TI  - New methods for multiple sclerosis drug discovery.
AB  - INTRODUCTION: MS is a heterogeneous disorder that requires the development of
      better diagnostics to identify disease subtypes enabling appropriate therapeutic
      intervention at an early stage of the disease. Accumulating evidence indicates
      that members of the inhibitor of apoptosis (IAP) family play an important role in
      the pathogenesis of MS by reducing the apoptotic elimination of autoreactive
      immune cells. AREAS COVERED: The authors describe improved animal modeling
      strategies to identify compounds that have immunomodulatory, neurorestorative and
      neuroprotective properties. In addition, the authors propose new approaches to
      better model cognitive dysfunction in MS, which will aid the development of novel
      therapeutics for this complex disorder. The paper provides the reader with an
      appreciation for the diagnostic and therapeutic potential of apoptosis-related
      proteins for MS. EXPERT OPINION: Recent evidence suggests that increased
      resistance of autoreactive immune cells to apoptotic elimination is a
      contributing factor to both disease susceptibility and progression in MS. This
      occurs, at least in part, because of elevated levels of the IAP family of anti
      apoptotic genes that display distinct expression profiles associated with
      different subtypes of MS. The authors believe that the detection and targeting of
      members of the IAP family can provide better drugs for MS. Particularly, the
      authors feel that the overexpression of IAPs in animal models can provide novel
      insights into MS for both its pathogenesis and the discovery of new lead
      compounds.

PMID- 22650978
TI  - Transformation of in vitro tools for kinase profiling: keeping an eye over the
      off-target liabilities.
AB  - INTRODUCTION: Over the past decade, there has been an increased number of FDA
      approved small molecule kinase inhibitors for the treatment of cancer. This is
      due, in part, to an increased understanding of the fundamental aspects of kinase
      biology, coupled with advances in the methods used to study the inhibitory
      effects of small molecules on kinase activity. Underlying the development of
      these inhibitors are profiling methods that are used to assess the effect of
      potential compounds against their desired and undesired targets. The advancement
      of kinase profiling has stemmed from the development of basic assay technology
      that allows compounds to be tested against ever larger panels of kinases in a
      robust, cost-effective manner. Methods have also been developed that rapidly
      assess compound activity against specific activation states of kinases. There has
      also been a development of newer methods that move beyond traditional biochemical
      formats, which take a 'whole cell' approach to compound profiling. AREAS COVERED:
      This review provides an overview of traditional biochemical-based kinase
      profiling as well as an introduction to advances that have been made by moving
      compound profiling into a cell-based format. EXPERT OPINION: While central to the
      appropriate prioritization and optimization of compounds during the hit to lead
      phase of early-stage pharmaceutical development, every compound profiling format
      must be critically assessed so that one can make informed decisions through an
      understanding of their strengths and limitations. These decisions will ultimately
      be balanced against cost, complexity and its biological relevance.

PMID- 22650979
TI  - Animal models of obsessive compulsive disorder: recent findings and future
      directions.
AB  - INTRODUCTION: Obsessive compulsive disorder (OCD) is a debilitating condition
      with limited treatment options. OCD is heterogeneous with respect to the content
      of obsessions and compulsions and their underlying motivation, among other
      characteristics. Animal models have provided important insights into the
      pathophysiology of OCD. AREAS COVERED: The phenomenology of OCD is discussed,
      with emphasis on clinically-relevant subgroups. The paper also discusses the
      advantages and limitations of animals as models of OCD, along with considerations
      on assessing their validity. A PubMed database search using the terms 'animal
      model' and 'obsessive compulsive disorder' revealed ongoing studies in several
      models, including stereotypy in the deer mouse, quinpirole-induced checking,
      spontaneous alternation, compulsive lever pressing, genetic models, pathogenic
      models and models involving normal compulsive-like behavioral patterns. These
      models are presented with respect to their similarity to specific features of OCD
      and the information gained from them. Studies in many of these models point to
      the participation of corticostriatal thalamocortical circuitry and
      corticostriatal glutamate neurotransmission in the pathophysiology of compulsive
      like behavior. EXPERT OPINION: The use of animal models takes us beyond simple
      serotonin- or dopamine-based models of OCD that are founded on the often limited,
      and still unexplained, response of OCD symptoms to serotonin reuptake inhibitors
      or antipsychotic therapy. Pharmacological challenges that selectively target
      neurochemical systems that modulate either corticostriatal glutamate or striatal
      dopamine neurotransmission, or indeed both, should be investigated in animal
      models of compulsive-like behavior. Such systems include metabotropic glutamate,
      adenosine and endocannabinoid receptors, among others.

PMID- 22650980
TI  - Advances in malignant glioma drug discovery.
AB  - INTRODUCTION: Outcome for patients with glioblastoma (GBM), the most common
      malignant primary brain tumor among adults, remains poor. However, two key
      treatment options have recently generated meaningful improvements in outcome for
      GBM patients. The addition of temozolomide (a methylating chemotherapeutic agent)
      to surgical resection and radiation therapy increases survival and is the first
      evidence that systemic chemotherapy can benefit GBM patients. Also, bevacizumab
      (a humanized mAb against VEGF) has significant antitumor activity among recurrent
      GBM patients. Additional areas of ongoing research are generating more
      therapeutic options that offer exciting potential to build on these results and
      further improve the outcome for malignant glioma patients. AREAS COVERED: This
      review describes three foci of advanced clinical research aimed at improving the
      outcome of GBM patients: protracted temozolomide dosing, VEGF-inhibiting agents
      and integrin inhibitors. This review also discusses potential clinical trial
      strategies to evaluate irreversible EGFR inhibitors as well as therapeutics
      targeting PI3K and the hedgehog signaling pathway. EXPERT OPINION: Several
      factors limit the efficacy of therapeutics targeting GBM. However, significant
      advances from basic science laboratories have recently generated important
      insights into the pathophysiology and molecular genetic abnormalities of these
      tumors. Efforts to translate these findings into innovative treatment strategies
      offer substantial promise to overcome therapeutic hurdles and treat individual
      patients more effectively. Improved understanding of malignant glioma biology and
      factors associated with treatment response will probably lead to improved
      therapeutic options and a better patient outcome.

PMID- 22650981
TI  - Experimental models for anxiolytic drug discovery in the era of omes and omics.
AB  - INTRODUCTION: Animal behavioral models have become an indispensable tool for
      studying anxiety disorders and testing anxiety-modulating drugs. However,
      significant methodological and conceptual challenges affect the translational
      validity and accurate behavioral dissection in such models. They are also often
      limited to individual behavioral domains and fail to target the disorder's real
      clinical picture (its spectrum or overlap with other disorders), which hinder
      screening and development of novel anxiolytic drugs. AREAS COVERED: In this
      article, the authors discuss and emphasize the importance of high-throughput
      multi-domain neurophenotyping based on the latest developments in video-tracking
      and bioinformatics. Additionally, the authors also explain how bioinformatics can
      provide new insight into the neural substrates of brain disorders and its benefit
      for drug discovery. EXPERT OPINION: The throughput and utility of animal models
      of anxiety and other brain disorders can be markedly increased by a number of
      ways: i) analyzing systems of several domains and their interplay in a wider
      spectrum of model species; ii) using a larger number of end points generated by
      video-tracking tools; iii) correlating behavioral data with genomic, proteomic
      and other physiologically relevant markers using online databases and iv)
      creating molecular network-based models of anxiety to identify new targets for
      drug design and discovery. Experimental models utilizing bioinformatics tools and
      online databases will not only improve our understanding of both gene-behavior
      interactions and complex trait interconnectivity but also highlight new targets
      for novel anxiolytic drugs.

PMID- 22650982
TI  - Multilevel analysis of environmental Salmonella prevalences and management
      practices on 49 broiler breeder farms in four south-eastern States, USA.
AB  - A two-part serial survey of 49 broiler breeder farms was conducted in four south
      eastern states: Arkansas, Alabama, Georgia and North Carolina. Broiler breeder
      farms from three to five broiler company complexes in each state were visited on
      two separate occasions to document management practices and perform environmental
      sampling for Salmonella prevalence estimation. Salmonella was detected in 88% of
      the broiler breeder houses that were sampled and was identified on all 49 farms
      enrolled. Many management characteristics were consistent across the different
      states and companies. Multilevel analysis was used to evaluate management
      characteristics as risk factors for Salmonella prevalence and to estimate the
      proportion of variance residing at the different hierarchical sampling levels.
      Management characteristics associated with increased Salmonella prevalence
      included treatment of the flock for any disease, having dusty conditions in the
      house, having dry conditions under the slats and walking through the house more
      than one time per day to pick-up dead birds. After adjusting for state as a fixed
      effect, the percentages of variance in Salmonella prevalence occurring at the
      complex, farm, visit, house and individual sample levels were 5.2%, 6.8%, 11.8%,
      2.8% and 73.4%, respectively. The intraclass correlations for samples collected
      from the same house; for samples from different houses during the same visit; for
      samples from different visits to the same farm; and for samples from different
      farms in the same complex were as follows: 0.27, 0.24, 0.12 and 0.05,
      respectively.

PMID- 22650983
TI  - Polymorphic variation of CYP11B2 predicts postoperative resolution of
      hypertension in patients undergoing adrenalectomy for aldosterone-producing
      adenomas.
AB  - OBJECTIVES: The surgical cure rate of patients with aldosterone-producing adenoma
      varies widely, and causes of persistent hypertension are not completely
      established. The objective of this study was to assess the blood pressure outcome
      in patients after retroperitoneoscopic adrenalectomy, and to analyze the CYP11B2
      344 C/T polymorphism and any factors associated with the outcome. METHODS:
      Between 2002 and 2009, 82 patients with unilateral aldosterone-producing adenoma
      underwent retroperitoneoscopic adrenalectomy. Clinical and biochemical data were
      reviewed retrospectively. Patients were investigated to assess the association of
      the CYP11B2 344 C/T polymorphism with resistant hypertension after surgery.
      RESULTS: Adrenalectomy cured hypertension in 44 patients (53.7%), and 27 patients
      (32.9%) had persistent hypertension that was much easier to control after
      surgery, whereas 11 patients (13.4%) had continued hypertension and poor blood
      pressure control. Multivariate regression analysis showed that the main
      determinants of postoperative cure were duration of hypertension less than 5
      years (OR 4.515, 95% CI 1.978-10.293), number of antihypertensive medications <=2
      (OR 2.639, 95% CI 1.154-6.035), preoperative response to spironolactone (OR
      3.105, 95% CI 1.381-6.985) and the TT genotype of the CYP11B2 gene (344 C/T; OR
      2.765, 95% CI 1.261-6.064). CONCLUSIONS: The 344 C/T polymorphism of the CYP11B2
      gene predicts resolution of hypertension in patients undergoing adrnelactomy for
      aldosterone-producing adenoma. Duration of hypertension, number of
      antihypertensive medications, and preoperative response to spironolactone also
      represents predictive factors that need to be considered for the identification
      of patients with continued postoperative hypertension requiring long-term
      monitoring and treatment.

PMID- 22650984
TI  - Interactions between dendrimers and ionic liquids revealed by pulsed field
      gradient and nuclear Overhauser effect NMR studies.
AB  - The host-guest interactions of cationic and anionic poly(amidoamine) (PAMAM)
      dendrimers with three ionic liquids including 1-butyl-3-methylimidazolium 2-(2
      methoxyethoxy)ethyl sulfate ([BMIM][MDEGSO(4)]), 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ([BMIM][TFSI]), and
      trihexyltetradecylphosphonium bis((trifluoromethyl)sulfonyl)imide ([THTDP][TFSI])
      were investigated by several NMR techniques such as (1)H and (19)F NMR, pulsed
      field gradient (PFG) NMR, and 2D nuclear Overhauser enhancement spectroscopy
      (NOESY). Anionic PAMAM dendrimer interacts with the ionic liquids via ionic
      interactions. However, almost no interaction is observed between cationic PAMAM
      dendrimer and the ionic liquids without pH adjustment. Besides, no inclusion
      formation between the PAMAM dendrimers and the ionic liquids is observed on the
      basis of NOE NMR studies. The interactions between dendrimers and ionic liquids
      are very different from those between dendrimers and surfactants or amphiphilic
      drugs. The results obtained from PFG and NOE studies provide new insights into
      dendrimer-based host-guest systems.

PMID- 22650987
TI  - A look at state-level risk assessment in the United States: making decisions in
      the absence of federal risk values.
AB  - State environmental agencies in the United States are charged with making risk
      management decisions that protect public health and the environment while
      managing limited technical, financial, and human resources. Meanwhile, the
      federal risk assessment community that provides risk assessment guidance to state
      agencies is challenged by the rapid growth of the global chemical inventory. When
      chemical toxicity profiles are unavailable on the U.S. Environmental Protection
      Agency's Integrated Risk Information System or other federal resources, each
      state agency must act independently to identify and select appropriate chemical
      risk values for application in human health risk assessment. This practice can
      lead to broad interstate variation in the toxicity values selected for any one
      chemical. Within this context, this article describes the decision-making process
      and resources used by the federal government and individual U.S. states. The risk
      management of trichloroethylene (TCE) in the United States is presented as a case
      study to demonstrate the need for a collaborative approach among U.S. states
      toward identification and selection of chemical risk values while awaiting
      federal risk values to be set. The regulatory experience with TCE is contrasted
      with collaborative risk science models, such as the European Union's efforts in
      risk assessment harmonization. Finally, we introduce State Environmental Agency
      Risk Collaboration for Harmonization, a free online interactive tool designed to
      help to create a collaborative network among state agencies to provide a vehicle
      for efficiently sharing information and resources, and for the advancement of
      harmonization in risk values used among U.S. states when federal guidance is
      unavailable.

PMID- 22650986
TI  - Progression of female reproductive stages associated with bipolar illness
      exacerbation.
AB  - OBJECTIVES: Late perimenopause and early postmenopause confer an increased risk
      of depression in the population, yet bipolar disorder mood course during these
      times remains unclear. METHODS: Clinic visits in 519 premenopausal, 116
      perimenopausal (including 13 women transitioning from perimenopause to
      postmenopause), and 133 postmenopausal women with bipolar disorder who received
      naturalistic treatment in the multisite Systematic Treatment Enhancement Program
      for Bipolar Disorder (STEP-BD) study over 19.8 +/- 15.5 months were analyzed for
      mood state. History of postpartum and perimenstrual mood exacerbation and current
      hormone therapy were evaluated as potential mood predictors. RESULTS: A
      progression in female reproductive stage (premenopause, perimenopause, and
      postmenopause) was significantly associated with percent of visits decreasing in
      euthymia (29.3%, 27.0%, 25.0%, respectively, p < 0.05), decreasing in syndromal
      mood elevation (5.3%, 4.1%, and 3.0%, respectively, p < 0.001), and increasing in
      subsyndromal symptoms (47.3%, 50.7%, and 52.7%, respectively, p = 0.05). Thirteen
      women transitioning from peri- to postmenopause had a significantly greater
      proportion of visits in syndromal depression (24.4%, p < 0.0005) compared to
      premenopausal, perimenopausal, and postmenopausal women, while depression in the
      latter three groups (18.1%, 18.1%, and 19.3%, respectively) did not differ.
      Perimenstrual and/or postpartum mood exacerbation, or hormone therapy did not
      significantly alter depression during perimenopause. CONCLUSIONS: A progression
      in female reproductive stages was associated with bipolar illness exacerbation. A
      small number of women transitioning from perimenopause to postmenopause had
      significantly greater depression than other female reproductive groups. Euthymia
      and mood elevation decreased with progressing female reproductive stage.
      Menstrual cycle or postpartum mood exacerbation, or current hormone therapy use,
      was not associated with perimenopausal depression. Future studies, which include
      hormonal assessments, are needed to confirm these preliminary findings.

PMID- 22650985
TI  - Glycines: role in alpha-helical membrane protein structures and a potential
      indicator of native conformation.
AB  - Among the growing number of membrane protein structures in the Protein Data Bank,
      there are many transmembrane domains that appear to be native-like; at the same
      time, there are others that appear to have less than complete native-like
      character. Hence, there is an increasing need for validation tools that
      distinguish native-like from non-native-like structures. Membrane mimetics used
      in protein structural characterizations differ in numerous physicochemical
      properties from native membranes and provide many opportunities for introducing
      non-native-like features into membrane protein structures. One possible approach
      for validating membrane protein structures is based on the use of glycine
      residues in transmembrane domains. Here, we have reviewed the membrane protein
      structure database and identified a set of benchmark proteins that appear to be
      native-like. In these structures, conserved glycine residues rarely face the
      lipid interstices, and many of them participate in close helix-helix packing.
      Glycine-based validation allowed the identification of non-native-like features
      in several membrane proteins and also shows the potential for verifying the
      native-like character for numerous other membrane protein structures.

PMID- 22650988
TI  - Calcyon, a mammalian specific NEEP21 family member, interacts with adaptor
      protein complex 3 (AP-3) and regulates targeting of AP-3 cargoes.
AB  - Calcyon is a neural enriched, single transmembrane protein that interacts with
      clathrin light chain and stimulates clathrin assembly and clathrin-mediated
      endocytosis. A similar property is shared by the heterotetrameric adaptor protein
      (AP) complexes AP-1, AP-2, and AP-3 which recruit cargoes for insertion into
      clathrin coated transport vesicles. Here we report that AP medium (MU) subunits
      interact with a YXXO-type tyrosine motif located at residues 133-136 in the
      cytoplasmic domain of calcyon. Site specific mutagenesis of the critical tyrosine
      and bulky hydrophobic residues tyrosine 133 and methionine 136 preferentially
      abrogated binding of the ubiquitous and neuronal isoforms of MU3, and also
      impacted MU1 and MU2 binding to a lesser degree. The relevance of these
      interactions was explored in vivo using mice harboring null alleles of calcyon.
      As seen in the mutagenesis studies, calcyon deletion in mice preferentially
      altered the subcellular distribution of AP-3 suggesting that calcyon could
      regulate membrane-bound pools of AP-3 and AP-3 function. To test this hypothesis,
      we focused on the hilar region of hippocampus, where levels of calcyon, AP-3, and
      AP-3 cargoes are abundant. We analyzed brain cryosections from control and
      calcyon null mice for zinc transporter 3 (ZnT3), and phosphatidylinositol-4
      kinase type II alpha (PI4KIIalpha), two well-defined AP-3 cargoes. Confocal
      microscopy indicated that ZnT3 and PI4KIIalpha are significantly reduced in the
      hippocampal mossy fibers of calcyon knock-out brain, a phenotype previously
      described in AP-3 deficiencies. Altogether, our data suggest that calcyon
      directly interacts with MU3A and MU3B, and regulates the subcellular distribution
      of AP-3 and the targeting of AP-3 cargoes.

PMID- 22650990
TI  - The relationship between vertical stimulation and horizontal attentional
      asymmetries.
AB  - The original aim was to examine the effect of perceived distance, induced by the
      Ponzo illusion, on left/right asymmetries for line bisection. In Experiment 1,
      university students (n = 29) made left/right bisection judgements for lines
      presented in the lower or upper half of the screen against backgrounds of the
      Ponzo stimuli, or a baseline. While the Ponzo illusion had relatively little
      effect on line bisection, elevation in the baseline condition had a strong
      effect, whereby the leftward bias was increased for upper lines. Experiment 2 (n
      = 17) eliminated the effect of elevation by presenting the line in the middle and
      moving the Ponzo stimuli relative to the line. Despite this change, the leftward
      bias was still stronger in the upper condition in the baseline condition. The
      final experiment (n = 17) investigated whether upper/lower visual stimulation,
      which was irrelevant to the task, affected asymmetries for line bisection. The
      results revealed that a rectangle presented in the upper half of the screen
      increased the leftward line bisection bias relative to a baseline and lower
      stimulation condition. These results corroborate neuroimaging research, showing
      increased right parietal activation associated with shifts of attention into the
      upper hemispace. This increased right parietal activation may increase the
      leftward attentional bias-resulting in a stronger leftward bias for line
      bisection.

PMID- 22650989
TI  - Application of RNA silencing to plant disease resistance.
AB  - To reduce the losses caused by plant pathogens, plant biologists have adopted
      numerous methods to engineer resistant plants. Among them, RNA silencing-based
      resistance has been a powerful tool that has been used to engineer resistant
      crops during the last two decades. Based on this mechanism, diverse approaches
      were developed. In this review, we focus on the application of RNA silencing to
      produce plants that are resistant to plant viruses such as RNA and DNA viruses,
      viroids, insects, and the recent expansion to fungal pathogens.

PMID- 22650991
TI  - Short-wavelength light beam in situ monitoring growth of InGaN/GaN green LEDs by
      MOCVD.
AB  - In this paper, five-period InGaN/GaN multiple quantum well green light-emitting
      diodes (LEDs) were grown by metal organic chemical vapor deposition with 405-nm
      light beam in situ monitoring system. Based on the signal of 405-nm in situ
      monitoring system, the related information of growth rate, indium composition and
      interfacial quality of each InGaN/GaN QW were obtained, and thus, the growth
      conditions and structural parameters were optimized to grow high-quality
      InGaN/GaN green LED structure. Finally, a green LED with a wavelength of 509 nm
      was fabricated under the optimal parameters, which was also proved by ex situ
      characterization such as high-resolution X-ray diffraction, photoluminescence,
      and electroluminescence. The results demonstrated that short-wavelength in situ
      monitoring system was a quick and non-destroyed tool to provide the growth
      information on InGaN/GaN, which would accelerate the research and development of
      GaN-based green LEDs.

PMID- 22651094
TI  - Structure & Methods.

PMID- 22651091
TI  - Catalytic asymmetric 5-enolexo aldolizations. A computational study.
AB  - The diastereo- and enantioselectivity obtained experimentally by Enders et all.
      (Enders, D.; Niemeier, O.; Straver, S. Synlett 2006, 3399-3402) in the amine
      catalyzed intramolecular 5-enolexo aldolization of 1,6-dicarbonyl compounds were
      fully rationalized using density functional theory methods. A polarizable
      continuum model was used to describe solvent effects. While 6-enolexo
      aldolizations are well described by Houk's model on the basis of steric and
      electrostatic contacts, the main factors conditioning the final selectivity in 5
      enolexo processes are calculated to be quite different. Thus, the selectivity
      results from the summation of several small electrostatic contacts with an
      unexpected HOMO electronic overlapping plus the ring strain of the five-membered
      ring, whereas steric effects seem to be unimportant. Our results indicate, in
      contrast with 6-enolexo processes, that high selectivities are not expected in
      this type of reaction and that the experimental selectivity shall be very
      dependent on the reaction conditions, as known experimental results seem to
      suggest. 7-enolendo products are not expected, as they are predicted to be formed
      by higher energetic transition states. Variable reaction rates, experimentally
      observed with different catalysts, are suggested to be mainly a result of
      different catalyst solubilities.

PMID- 22651096
TI  - A QMCF-MD investigation of the structure and dynamics of Ce4+ in aqueous
      solution.
AB  - A quantum-mechanical charge-field molecular dynamics simulation has been
      performed for a tetravalent Ce ion in aqueous solution. In this framework, the
      complete first and second hydration spheres are treated by ab initio quantum
      mechanics supplemented by an electrostatic embedding technique, making the
      construction of non-Coulombic solute-solvent potentials unnecessary. During the
      10 ps of simulation time, the structural aspects of the solution were analyzed by
      various methods. Experimental results such as the mean Ce-O bond distance and the
      predicted first-shell coordination number were compared to the results obtained
      from the simulation resolving some ambiguities in the literature. The dynamics of
      the system were characterized by mean ligand residence times and frequency/force
      constant calculations. Furthermore, Ce-O and Ce-H angular radial distribution
      plots were employed, yielding deeper insight into the structural and dynamical
      aspects of the system.

PMID- 22651090
TI  - Redox properties of the disulfide bond of human Cu,Zn superoxide dismutase and
      the effects of human glutaredoxin 1.
AB  - The intramolecular disulfide bond in hSOD1 [human SOD1 (Cu,Zn superoxide
      dismutase 1)] plays a key role in maintaining the protein's stability and
      quaternary structure. In mutant forms of SOD1 that cause familial ALS
      (amyotrophic lateral sclerosis), this disulfide bond is more susceptible to
      chemical reduction, which may lead to destabilization of the dimer and
      aggregation. During hSOD1 maturation, disulfide formation is catalysed by CCS1
      (copper chaperone for SOD1). Previous studies in yeast demonstrate that the yeast
      GSH/Grx (glutaredoxin) redox system promotes reduction of the hSOD1 disulfide in
      the absence of CCS1. In the present study, we probe further the interaction
      between hSOD1, GSH and Grxs to provide mechanistic insight into the redox
      kinetics and thermodynamics of the hSOD1 disulfide. We demonstrate that hGrx1
      (human Grx1) uses a monothiol mechanism to reduce the hSOD1 disulfide, and the
      GSH/hGrx1 system reduces ALS mutant SOD1 at a faster rate than WT (wild-type)
      hSOD1. However, redox potential measurements demonstrate that the thermodynamic
      stability of the disulfide is not consistently lower in ALS mutants compared with
      WT hSOD1. Furthermore, the presence of metal cofactors does not influence the
      disulfide redox potential. Overall, these studies suggest that differences in the
      GSH/hGrx1 reaction rate with WT compared with ALS mutant hSOD1 and not the
      inherent thermodynamic stability of the hSOD1 disulfide bond may contribute to
      the greater pathogenicity of ALS mutant hSOD1.

PMID- 22651098
TI  - Precise pattern replication of polymer blends into nonuniform geometries via
      reducing interfacial tension between two polymers.
AB  - Patterned polymer structures with different functionalities have many potential
      applications. Directed assembly of polymer blends using chemically functionalized
      patterns during spin-coating has been used to fabricate the patterned polymer
      structures. For bridging the gap between laboratorial experiments and
      manufacturing of nanodevices, the polymer blends structures are required to be
      precisely patterned into nonuniform geometries in a high-rate process, which
      still is a challenge. In this Article, we demonstrated for the first time that by
      decreasing the interfacial tension between two polymers polystyrene and
      poly(acrylic acid) via adding a compatibilizer (polystyrene-b-poly(acrylic acid)
      ), a polystyrene/poly(acrylic acid)  blend was precisely patterned into
      nonuniform geometries in a high-rate fashion. The patterned nonuniform geometries
      included angled lines with angles varied from 30 degrees  to 150 degrees , T
      junctions, square arrays, circle arrays, and arbitrary letter-shaped geometries.
      The reduction in the interfacial tension improved the line edge roughness and the
      patterning efficiency of the patterned polymer blends. In addition, the
      commensurability between characteristic length and pattern periodicity for well
      ordered morphologies was also expanded with decreasing interfacial tension. This
      approach can be easily extended to other functional polymers in a blend and
      facilitate the applications of patterned polymer structures in biosensors,
      organic thin-film electronics, and polymer solar cells.

PMID- 22651097
TI  - Use of black vulture (Coragyps atratus) in complementary and alternative
      therapies for cancer in Colombia: a qualitative study.
AB  - BACKGROUND: Although Coragyps atratus has been used as a traditional therapy for
      patients with cancer, the scientific literature does not contain enough
      information on how this therapy is used or the mechanisms that explain this
      therapeutic practice. OBJECTIVES: To understand the methods of use and the
      reasons given by patients and caregivers for the use of Coragyps atratus in
      cancer treatment. METHODS: This study used a qualitative design based on twenty
      in-depth interviews of patients with cancer or caregivers of patients with the
      disease. The analysis of the text was based on an inductive thematic approach.
      RESULTS: Resistance to disease and immune enhancement are properties attributed
      to Coragyps atratus when used for cancer treatment. The most recommended method
      of use is fresh blood ingestion, and the associated mechanism of action is
      transfer of immune factors to the individual who consumes it. CONCLUSIONS: Use of
      Coragyps atratus as a treatment for cancer is a popular alternative therapy in
      Colombia. More studies are needed to understand the clinical effects of this
      intervention in cancer patients.

PMID- 22651099
TI  - Quantity and size distribution of cough-generated aerosol particles produced by
      influenza patients during and after illness.
AB  - The question of whether influenza is transmitted to a significant degree by
      aerosols remains controversial, in part, because little is known about the
      quantity and size of potentially infectious airborne particles produced by people
      with influenza. In this study, the size and amount of aerosol particles produced
      by nine subjects during coughing were measured while they had influenza and after
      they had recovered, using a laser aerosol particle spectrometer with a size range
      of 0.35 to 10 MUm. Individuals with influenza produce a significantly greater
      volume of aerosol when ill compared with afterward (p = 0.0143). When the
      patients had influenza, their average cough aerosol volume was 38.3 picoliters
      (pL) of particles per cough (SD 43.7); after patients recovered, the average
      volume was 26.4 pL per cough (SD 45.6). The number of particles produced per
      cough was also higher when subjects had influenza (average 75,400
      particles/cough, SD 97,300) compared with afterward (average 52,200, SD 98,600),
      although the difference did not reach statistical significance (p = 0.1042). The
      average number of particles expelled per cough varied widely from patient to
      patient, ranging from 900 to 302,200 particles/cough while subjects had influenza
      and 1100 to 308,600 particles/cough after recovery. When the subjects had
      influenza, an average of 63% of each subject's cough aerosol particle volume in
      the detection range was in the respirable size fraction (SD 22%), indicating that
      these particles could reach the alveolar region of the lungs if inhaled by
      another person. This enhancement in aerosol generation during illness may play an
      important role in influenza transmission and suggests that a better understanding
      of this phenomenon is needed to predict the production and dissemination of
      influenza-laden aerosols by people infected with this virus.   [Supplementary
      materials are available for this article. Go to the publisher's online edition of
      Journal of Occupational and Environmental Hygiene for the following free
      supplemental resources: a PDF file of demographic information, influenza test
      results, and volume and peak flow rate during each cough and a PDF file
      containing number and size of aerosol particles produced.].

PMID- 22651100
TI  - Long working hours and metabolic syndrome among Japanese men: a cross-sectional
      study.
AB  - BACKGROUND: The link between long working hours and health has been extensively
      studied for decades. Despite global concern regarding metabolic syndrome,
      however, no studies to date have solely evaluated the relationship between long
      working hours and that syndrome. We therefore examined the association between
      long working hours and metabolic syndrome in a cross-sectional study. METHODS:
      Between May and October 2009, we collected data from annual health checkups and
      questionnaires from employees at a manufacturing company in Shizuoka, Japan.
      Questionnaires were returned by 1,601 workers (response rate: 96.2%; 1,314 men,
      287 women). After exclusions, including women because of a lack of overtime work,
      the analysis was performed for 933 men. We calculated odds ratios (ORs) and 95%
      confidence intervals (CIs) for metabolic syndrome. Further, we conducted a
      stratified analysis by age-group (<40 years vs. >= 40 years). RESULTS: Metabolic
      syndrome was identified in 110 workers (11.8%). We observed a positive
      association between working hours and metabolic syndrome after adjusting for age,
      occupation, shift work, smoking status, frequency of alcohol consumption, and
      cohabiting status. Compared with subjects who worked 7-8 h/day, multivariate ORs
      for metabolic syndrome were 1.66 (95% CI, 0.91-3.01), 1.48 (95% CI, 0.75-2.90),
      and 2.32 (95% CI, 1.04-5.16) for those working 8-9 h/day, 9-10 h/day, and >10
      h/day, respectively. Similar patterns were obtained when we excluded shift
      workers from the analysis. In age-stratified analysis, the corresponding ORs
      among workers aged >= 40 years were 2.02 (95% CI, 1.04-3.90), 1.21 (95% CI, 0.53
      2.77), and 3.14 (95% CI, 1.24-7.95). In contrast, no clear association was found
      among workers aged <40 years. CONCLUSIONS: The present study suggests that 10
      h/day may be a trigger level of working hours for increased risk of metabolic
      syndrome among Japanese male workers.

PMID- 22651101
TI  - MPTP modulates hippocampal synaptic transmission and activity-dependent synaptic
      plasticity via dopamine receptors.
AB  - Parkinson's disease (PD)-like symptoms and cognitive deficits are inducible by 1
      methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Since cognitive abilities,
      including memory formations rely also on hippocampus, we set out to clarify the
      effects of MPTP on hippocampal physiology. We show that bath-application of MPTP
      (25 MUM) to acute hippocampal slices enhanced AMPA receptor-mediated field
      excitatory postsynaptic potentials (AMPAr-fEPSPs) transiently, whereas N-methyl-D
      aspartate (NMDA) receptor-mediated fEPSPs (NMDAr-fEPSPs) were facilitated
      persistently. The MPTP-mediated transient AMPAr-fEPSP facilitation was
      antagonized by the dopamine D2-like receptor antagonists, eticlopride (1 MUM) and
      sulpiride (1 and 40 MUM). In contrast, the persistent enhancement of NMDAr-fEPSPs
      was prevented by the dopamine D1-like receptor antagonist SCH23390 (10 MUM). In
      addition, we show that MPTP decreased paired-pulse facilitation of fEPSPs and
      mEPSCs frequency. Regarding activity-dependent synaptic plasticity, 25 MUM MPTP
      transformed short-term potentiation (STP) into a long-term potentiation (LTP) and
      caused a slow onset potentiation of a non-tetanized synaptic input after
      induction of LTP in a second synaptic input. This heterosynaptic slow onset
      potentiation required activation of dopamine D1-like and NMDA-receptors. We
      conclude that acute MPTP application affects basal synaptic transmission by
      modulation of presynaptic vesicle release and facilitates NMDAr-fEPSPs as well as
      activity-dependent homo- and heterosynaptic plasticity under participation of
      dopamine receptors.

PMID- 22651103
TI  - Intramolecular sigma-bond metathesis between carbon-carbon and silicon-silicon
      bonds.
AB  - An intramolecular sigma-bond metathesis between carbon-carbon and silicon-silicon
      bonds took place on treatment of a disilane tethered to a cyclobutanone with a
      palladium(0) catalyst, furnishing a silaindane skeleton as well as an acylsilane
      functionality at once.

PMID- 22651102
TI  - The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA
      NCAM in offspring born to kindled rats.
AB  - BACKGROUND: Maternal epileptic seizures during pregnancy can affect the
      hippocampal neurons in the offspring. The polysialylated neural cell adhesion
      molecule (PSA-NCAM), which is expressed in the developing central nervous system,
      may play important roles in neuronal migration, synaptogenesis, and axonal
      outgrowth. This study was designed to assess the effects of kindling either with
      or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring.
      METHODS: Forty timed-pregnant Wistar rats were divided into four groups: A)
      Kind+/Seiz+, pregnant kindled (induced two weeks prior to pregnancy) rats that
      received repeated intraperitoneal (i.p.) pentylenetetrazol, PTZ injections on
      gestational days (GD) 14-19; B) Kind-/Seiz+, pregnant non-kindled rats that
      received PTZ injections on GD14-GD19; C) Kind+/Seiz-, pregnant kindled rats that
      did not receive any PTZ injections; and D) Kind-/Seiz-, the sham controls.
      Following birth, the pups were sacrificed on PD1 and PD14, and PSA-NCAM
      expression and localization in neonates' hippocampi were analyzed by Western
      blots and immunohistochemistry. RESULTS: Our data show a significant down
      regulation of hippocampal PSA-NCAM expression in the offspring of Kind+/Seiz+ (p
      = 0.001) and Kind-/Seiz+ (p = 0.001) groups compared to the sham control group.
      The PSA-NCAM immunoreactivity was markedly decreased in all parts of the
      hippocampus, especially in the CA3 region, in Kind+/Seiz+ (p = 0.007) and Kind
      /Seiz+ (p = 0.007) group's newborns on both PD1 and 14. CONCLUSION: Our findings
      demonstrate that maternal seizures but not kindling influence the expression of
      PSA-NCAM in the offspring's hippocampi, which may be considered as a factor for
      learning/memory and cognitive impairments reported in children born to epileptic
      mothers.

PMID- 22651104
TI  - Note on special technical issue on adaptive designs for clinical trials.

PMID- 22651105
TI  - On efficient two-stage adaptive designs for clinical trials with sample size
      adjustment.
AB  - Group sequential designs are rarely used for clinical trials with substantial
      over running due to fast enrollment or long duration of treatment and follow-up.
      Traditionally, such trials rely on fixed sample size designs. Recently, various
      two-stage adaptive designs have been introduced to allow sample size adjustment
      to increase statistical power or avoid unnecessarily large trials. However, these
      adaptive designs can be seriously inefficient. To address this infamous problem,
      we propose a likelihood-based two-stage adaptive design where sample size
      adjustment is derived from a pseudo group sequential design using cumulative
      conditional power. We show through numerical examples that this design cannot be
      improved by group sequential designs. In addition, the approach may uniformly
      improve any existing two-stage adaptive designs with sample size adjustment. For
      statistical inference, we provide methods for sequential p-values and confidence
      intervals, as well as median unbiased and minimum variance unbiased estimates. We
      show that the claim of inefficiency of adaptive designs by Tsiatis and Mehta (
      2003 ) is logically flawed, and thereby provide a strong defense of Cui et al. (
      1999 ).

PMID- 22651106
TI  - Optimization of adaptive designs: efficiency evaluation.
AB  - The rising cost of clinical trials is impeding the development of new drugs.
      There is an acute need for critical evaluation and innovate thinking while
      designing the trial. Adaptive design has been repeatedly called upon in the last
      decade as one of the prescriptions for this intricate problem. From a pure
      statistical perspective, the adaptive design framework depends heavily on the
      appropriate selection of the type of test statistics and stopping boundaries.
      There are several methods proposed in the literature, based on different test
      statistics and stopping boundaries. All of these methods are rigorous in
      controlling type I error. In this paper, we group combination p-value methods
      into major categories along with their stopping boundaries. We review and compare
      these methods based on their operating characteristics, including average sample
      size and maximum sample size under null and alternative hypothesis, power, and
      early stopping probabilities. The optimal interim analysis timing and alpha
      spending function were used as the independent factors for this assessment. We
      propose an evaluation matrix and establish a framework to assess the most
      efficient design in order to assist in "one stop shopping."

PMID- 22651107
TI  - Adaptive group sequential test with changing patient population.
AB  - Standard group sequential test assumes that the treatment effects are homogeneous
      over time. In practice, however, this assumption may be violated. Often, this
      occurs when treatment effects are heterogeneous in patients with different
      prognostic groups, which are not evenly distributed over the time course of the
      group sequential trial. In this article, we consider a setting where the
      inclusion/exclusion criteria for patient entry are relaxed at interim analyses.
      This triggers heterogeneous treatment effects over the enlarged patient
      population. In particular, we assume that the population change relates to some
      baseline covariates. Simulation results show that the type I error can be
      severely inflated if adjustment is not made to the statistical analysis. We
      consider a set of linear regression models. With these models, we make inference
      on the target population based on all data from the changed populations. The
      proposed method leads to unbiased inference.

PMID- 22651108
TI  - Sample size adaptation in fixed-dose combination drug trial.
AB  - Statistical testing in clinical trials can be complex when the statistical
      distribution of the test statistic involves a nuisance parameter. Some type of
      nuisance parameters such as standard deviation of a continuous response variable
      can be handled without too much difficulty. Other type of nuisance parameters,
      specifically associated with the main parameter under testing, can be difficult
      to handle. Without knowledge of the possible value of such a nuisance parameter,
      the maximum type I error associated with testing the main parameter may occur at
      an extreme value of the nuisance parameter. A well known example is the
      intersection-union test for comparing a combination drug with its two component
      drugs where the nuisance parameter is the mean difference between the two
      components. Knowledge of the possible range of value of this mean difference may
      help enhance the clinical trial design. For instance, if the interim internal
      data suggest that this mean difference falls into a possible range of value, then
      the sample size may be reallocated after the interim look to possibly improve the
      efficiency of statistical testing. This research sheds some light into possible
      power advantage from such a sample size reallocation at the interim look.

PMID- 22651109
TI  - On adaptive error spending approach for group sequential trials with random
      information levels.
AB  - A group sequential analysis following the error spending approach of Lan and
      DeMets ( 1983 ) requires that the maximum information level be fixed in advance.
      In practice, however, the maximum information level is often random, making it
      impossible to determine the information fractions required by Lan and DeMets (
      1983 ) to calculate the sequential boundary. We propose an adaptive error
      spending approach that further expands practical applications to settings where
      the interim information levels can depend on blinded accumulating data. We use a
      simple weighting method to combine independent test statistics from different
      stages, which are then compared with adaptive boundary values for the group
      sequential test. We develop a measure-theoretic framework and show that the
      adaptive error spending approach controls the type 1 error rates. Methods for
      point estimates and confidence intervals are also proposed. We warn that an error
      spending approach can lead to serious inflation of the type 1 error rates when
      the number or timing of interim analyses is allowed to depend on unblinded
      accumulating data.

PMID- 22651110
TI  - Estimation of treatment effect following a clinical trial with adaptive design.
AB  - Parameter estimation following an adaptive design or group sequential design has
      been extremely challenging due to potential random high from its face value
      estimate. In this paper, we introduce a new framework to model clinical trial
      data flow based on a marked point process (MPP). The MPP model allows us to use
      methods of stochastic calculus for analyses of any adaptive clinical trial. As an
      example, we apply this method to a two stage treatment selection design and
      derive a procedure to estimate the treatment effect. Numerical examples will be
      used to evaluate the performance of the proposed procedure.

PMID- 22651111
TI  - Adaptive randomization for clinical trials.
AB  - In February 2010, the U.S. Food and Drug Administration (FDA,  2010 ) drafted
      guidance that discusses the statistical, clinical, and regulatory aspects of
      various adaptive designs for clinical trials. An important class of adaptive
      designs is adaptive randomization, which is considered very briefly in subsection
      VI.B of the guidance. The objective of this paper is to review several important
      new classes of adaptive randomization procedures and convey information on the
      recent developments in the literature on this topic. Much of this literature has
      been focused on the development of methodology to address past criticisms and
      concerns that have hindered the broader use of adaptive randomization. We
      conclude that adaptive randomization is a very broad area of experimental design
      that has important application in modern clinical trials.

PMID- 22651112
TI  - Doubly randomized delayed-start design for enrichment studies with responders or
      nonresponders.
AB  - High placebo response has been a major source of bias and is difficult to deal
      with in many central nervous system (CNS) clinical trials. This bias has led to a
      high failure rate in mood disorder trials even with known effective drugs. For
      cancer trials, the traditional parallel group design biases the inference on the
      maintenance effect of the new drug with the traditional time-to-treatment failure
      analysis. To minimize bias, we propose a doubly randomized delayed-start design
      for clinical trials with enrichment. The design consists of two periods. In the
      first period, patients can be randomized to receive several doses of a new drug
      or a control. In the second period, control patients of the first period of an
      enriched population can be rerandomized to receive the same or fewer doses of the
      new drug or to continue on the control. Depending on the clinical needs,
      different randomization ratios can be applied to the two periods. The essential
      feature is that the design is naturally adaptive because of the randomization for
      the second period. As a result, other aspects of the second period, such as the
      sample size, can be modified adaptively when an interim analysis is set up for
      the first period. At the end of the trial, response data from both randomizations
      are combined in an integrated analysis. Because of the enrichment in the second
      period, the design increases the probability of trial success and, in addition,
      reduces the required sample size. Thus, for clinical development, the design
      offers greater efficiency.

PMID- 22651114
TI  - Analysis of time-to-event data with nonuniform patient entry and loss to follow
      up under a two-stage seamless adaptive design with weibull distribution.
AB  - In the pharmaceutical industry, a two-stage seamless adaptive design that
      combines two separate independent clinical trials into a single clinical study is
      commonly employed in clinical research and development. In practice, in the
      interest of shortening the development process, it is not uncommon to consider
      study endpoints with different treatment durations at different stages (Chow and
      Chang,  2006 ; Maca et al.,  2006 ). In this study, our attention is placed on
      the case where the study endpoints of interest are time-to-event data where the
      durations at the two stages are different with nonuniform patient entry and
      losses to follow-up or dropouts. Test statistics for the final analysis based on
      the combined data are developed under various hypotheses for testing equality,
      superiority, noninferiority, and equivalence. In addition, formulas for sample
      size calculation and allocation between the two stages based on the proposed test
      statistic are derived.

PMID- 22651113
TI  - Flexible analytical methods for adding a treatment arm mid-study to an ongoing
      clinical trial.
AB  - It is not uncommon to have experimental drugs under different stages of
      development for a given disease area. Methods are proposed for use when another
      treatment arm is to be added mid-study to an ongoing clinical trial. Monte Carlo
      simulation was used to compare potential analytical approaches for pairwise
      comparisons through a difference in means in independent normal populations
      including (1) a linear model adjusting for the design change (stage effect), (2)
      pooling data across the stages, or (3) the use of an adaptive combination test.
      In the presence of intra-stage correlation (or a non-ignorable fixed stage
      effect), simply pooling the data will result in a loss of power and will inflate
      the type I error rate. The linear model approach is more powerful, but the
      adaptive methods allow for flexibility (re-estimating sample size). The
      flexibility to add a treatment arm to an ongoing trial may result in cost savings
      as treatments that become ready for testing can be added to ongoing studies.

PMID- 22651115
TI  - Adaptive randomization to improve utility-based dose-finding with bivariate
      ordinal outcomes.
AB  - A sequentially outcome-adaptive Bayesian design is proposed for choosing the dose
      of an experimental therapy based on elicited utilities of a bivariate ordinal
      (toxicity, efficacy) outcome. Subject to posterior acceptability criteria to
      control the risk of severe toxicity and exclude unpromising doses, patients are
      randomized adaptively among the doses having posterior mean utilities near the
      maximum. The utility increment used to define near-optimality is nonincreasing
      with sample size. The adaptive randomization uses each dose's posterior
      probability of a set of good outcomes, defined by a lower utility cutoff.
      Saturated parametric models are assumed for the marginal dose-toxicity and dose
      efficacy distributions, allowing the possible requirement of monotonicity in
      dose, and a copula is used to obtain a joint distribution. Prior means are
      computed by simulation using elicited outcome probabilities, and prior variances
      are calibrated to control prior effective sample size and obtain a design with
      good operating characteristics. The method is illustrated by a Phase I/II trial
      of radiation therapy for children with brainstem gliomas.

PMID- 22651116
TI  - A two-dimensional search algorithm for dose-finding trials of two agents.
AB  - Existing algorithms for identifying the maximum tolerated combination in dose
      finding trials of two agents are mostly one-dimensional. Moreover, these
      algorithms use only the frequency of observed dose-limiting toxicities as the
      basis for dose escalations and deescalations. In this article, we propose a two
      dimensional algorithm that uses not only the frequency but also the source of
      dose-limiting toxicities to direct dose escalations and deescalations. In
      addition, when the doses of both agents are escalated simultaneously, a more
      conservative design replaces a default aggressive design to evaluate the
      resulting dose combination. Our method aims to increase in-trial patient safety
      without unnecessary increase in sample size.

PMID- 22651117
TI  - Sample size estimation in single-arm clinical trials with multiple testing under
      frequentist and Bayesian approaches.
AB  - In this paper, we study one-sided multiple testing problems for normal and
      binomial distributions. We use order statistics to test the null hypothesis {all
      H ( i0) are true}. This approach allows us to uniformly address frequentist and
      Bayesian multiple testing models. To calculate order statistics, we use
      confidence limits. In frequentist models, we apply an adjustment to the
      confidence limits that is equivalent to the Bonferroni adjustment of p-values. In
      the Bayesian case, we adjust the credible limits following a concept of
      reconciliation between the Bayesian posterior probability and the frequentist p
      value. We also study the quantitative relationship between the number of tests
      and the sample size of a clinical trial. If the number of tests is very large, we
      suggest using asymptotic order statistics. We study the performance of these
      statistics. The asymptotic order statistics for the normal distribution are used
      to extend the results for independent observations to dependent observations.

PMID- 22651118
TI  - Minimizing the maximum expected sample size in two-stage Phase II clinical trials
      with continuous outcomes.
AB  - Two-stage designs are commonly used for Phase II trials. Optimal two-stage
      designs have the lowest expected sample size for a specific treatment effect, for
      example, the null value, but can perform poorly if the true treatment effect
      differs. Here we introduce a design for continuous treatment responses that
      minimizes the maximum expected sample size across all possible treatment effects.
      The proposed design performs well for a wider range of treatment effects and so
      is useful for Phase II trials. We compare the design to a previously used optimal
      design and show it has superior expected sample size properties.

PMID- 22651119
TI  - On the independence of data monitoring committee in adaptive design clinical
      trials.
AB  - In clinical trials, an independent data monitoring committee (DMC) is often
      established to perform both ongoing safety data monitoring and interim efficacy
      analysis. These evaluations are performed in a blinded fashion in order to avoid
      possible operational biases that may be introduced to the trial after the review
      of the data. The DMCs for clinical trials using adaptive design methods are also
      positioned to implement the adaptation decision according to the prospective
      adaptation algorithm. While the DMC plays an important role in maintaining the
      validity and integrity of the intended clinical trial, adaptive design clinical
      trials trigger a greater role and increased responsibility for the DMC. To assist
      the sponsor in establishing a DMC, the U.S. Food and Drug Administration (FDA)
      published a draft guidance entitled Establishment and Operation of Clinical Trial
      Data Monitoring Committees in 2006. In this article, the composition,
      role/responsibility, and function/activity of a DMC are described. Concerns of
      the additional responsibilities of the DMC for adaptive design clinical trials
      are addressed. Although the intention of the DMC is well-intentioned,
      controversial issues inevitably occur. These controversial issues include, but
      are not limited to, (1) the challenge of the independence of a DMC and (2) the
      issue regarding the direct communication between the DMC and the FDA. Discussion
      of controversial issues and practical issues are also provided.

PMID- 22651123
TI  - Using artificial neural networks to predict cell-penetrating compounds.
AB  - INTRODUCTION: Membrane-cell penetration is a key property for drug candidates,
      particularly those related to CNS and gastrointestinal diseases. The ability to
      know whether a drug or compound has the ability to perform this complex
      characteristic in advance would save time and money for pharmaceutical companies.
      One robust and fast solution is to use artificial neural networks (ANNs) to
      predict the cell penetration of the compound candidates. AREAS COVERED: The
      authors review the application of ANN methods for ANN modeling in the discovery
      of cell-penetrating drugs. The article looks at three main systems including the
      BBB, gastrointestinal absorption and permeation in addition to discussing a new
      approach for cell-penetrating peptide discovery. This review provides the reader
      with an overview of the ANN methods and applications for the broader audience
      interested in prediction of cell penetration of drugs. EXPERT OPINION: ANNs can
      be successfully applied to the prediction of cell-penetrating drugs. Researchers
      have a broad field of applications for the use of quantitative structure-activity
      relationship neural networks in drug discovery and development, and can use these
      areas to further investigate this important pharmaceutical topic.

PMID- 22651124
TI  - Ligand functional selectivity and quantitative pharmacology at G protein-coupled
      receptors.
AB  - INTRODUCTION: In recent years, it has become clear that individual GPCRs can
      elicit multiple G-protein-dependent and -independent cellular responses. This has
      led to the discovery that certain ligands can differentially modulate these
      responses, a concept known as functional selectivity. AREAS COVERED: In this
      review, the authors describe the various manifestations of functional selectivity
      and its potential implication in drug discovery. The authors provide a historical
      perspective of the observations and methodologies that led to the evolution of
      this concept. The authors also describe the proposed molecular mechanisms
      responsible for the engagement of distinct subsets of signaling repertoire by
      different ligands. The review offers the reader a synthetic view of how
      functional selectivity could be used in the design of safer and more effective
      drugs. EXPERT OPINION: Our better understanding of the various ways by which
      compounds modulate GPCR activity has led to a parallel expansion of the
      terminology used to describe these phenomena. The authors propose a
      standardization of this nomenclature as an essential step to both simplify and
      clarify the language used among researchers to facilitate future collaboration
      and discovery of these important therapeutic targets. Such clarification of the
      various aspects of functional selectivity, coupled with the development of tools
      for effective monitoring, will undoubtedly bring this emerging concept into the
      general paradigm of drug discovery at GPCRs.

PMID- 22651125
TI  - Developments in the discovery of drugs for spinal muscular atrophy: successful
      beginnings and future prospects.
AB  - INTRODUCTION: Spinal muscular atrophy (SMA) is an autosomal recessive disease
      caused by mutations in a gene that produces a protein called survival motor
      neuron (SMN). SMN has an important role in snRNP assembly in all cells but that
      may not be its only role; the reasons for SMN deficiency resulting in
      neuromuscular dysfunction and motor neuron degeneration remain active areas of
      research. Besides increasing SMN, compensating for SMN deficiencies or
      neuroprotection may be therapeutic options for SMA. Age of onset and the rate of
      disease progression are variable and therapeutic strategies should be appropriate
      to subtypes of SMA patients. AREAS COVERED: The article discusses SMA, their
      targets and where these targets can be found. Additionally, the article reviews
      small molecules identified as disease modifiers and how these small molecules
      were discovered. The article also describes and discusses emerging concepts
      regarding the disease mechanisms. The author compiled this review using
      scientific literature, patent databases, company and patient association and
      government websites. EXPERT OPINION: Small molecules targeting various processes
      implicated in SMA are reaching the clinic. These molecules and targets, although
      not yet validated, are providing insight into the complexity of a 'simple'
      genetic disease such as SMA. SMA is not a single disease and so various
      therapeutic strategies are needed. Biomarkers and regulatory guidelines are
      required to select patients for clinical trials, decide when to initiate
      treatment and how to develop combinations of investigational drugs.

PMID- 22651126
TI  - Navigating tuberculosis drug discovery with target-based screening.
AB  - INTRODUCTION: Mycobacterium tuberculosis kills more people than any other
      bacterial pathogen. New drugs are required to shorten the treatment time and
      provide a viable therapy for drug-resistant and latent forms of tuberculosis. The
      tuberculosis field has advanced considerably since the publication of the M.
      tuberculosis genome sequence. Today, researchers can build a high definition map
      of the pathogen's traits and behavior and select individual targets for chemical
      disruption. AREAS COVERED: This review examines the discovery of current clinical
      and candidate tuberculosis drugs. It outlines recent developments in the
      selection of molecular targets for the discovery of new anti-mycobacterial
      agents. It appraises techniques that incorporate target knowledge into the
      screening protocol. These techniques include in silico, in vitro enzyme-based,
      differential antisense sensitivity and gene expression screening systems. The
      review also looks ahead to further techniques that may be applied in tuberculosis
      drug discovery. EXPERT OPINION: The adoption of an 'either/or' approach to
      targeted or random tuberculosis drug screening is not expected. The historical
      success of random screening in providing the tuberculosis drugs currently in
      clinical use is likely to ensure that non-targeted protocols retain an important
      role in drug screening. However, a number of M. tuberculosis inhibitors in lead
      optimization and preclinical development have been discovered using targeted
      methods. Realization of the first clinically-approved tuberculosis drugs derived
      from targeted screening and continued refinements in targeted screening
      technologies are likely to increase the adoption of targeted approaches in the
      future.

PMID- 22651127
TI  - Preclinical development of dipeptidyl peptidase IV inhibitor alogliptin: a brief
      overview.
AB  - INTRODUCTION: Alogliptin is a pyrimidinedione-based potent and selective
      inhibitor of DPP IV that was discovered by Syrrx (Takeda San Diego) for the
      treatment of type 2 diabetes mellitus (T2D). Alogliptin is currently launched in
      Japan with the results of its clinical trials indicating that it is generally
      well tolerated and shows relatively fewer adverse side effects than other
      existing therapies for T2D. AREAS COVERED: The objective of the present review is
      to provide an overview of the various stages of preclinical development, for
      example, design, molecular modeling studies, synthesis and in vitro/in vivo
      pharmacological evaluation of alogliptin. An extensive literature search was
      conducted to collect abstracts, publications, patents and presentations from
      various sources. The authors review the information related to the preclinical
      development of alogliptin and summarize and present the relevant results. EXPERT
      OPINION: Alogliptin has shown greater in vitro selectivity for DPP IV over
      closely related enzymes, including DPP VIII and DPP IX, in comparison with other
      launched DPP IV inhibitors such as sitagliptin, saxagliptin and vildagliptin.
      Alogliptin has been evaluated in different diabetic animal models and is found to
      reduce glycosylated hemoglobin, plasma glucose, glucagon and triglycerides
      levels. Alogliptin also ameliorates beta-cell function, with a significant
      increase in plasma insulin levels. The authors believe that this potent and
      selective inhibitor of DPP IV could compete with traditional oral anti-diabetic
      therapies in the future.

PMID- 22651128
TI  - Perception and communication of flood risks: a systematic review of empirical
      research.
AB  - Flood hazards are the most common and destructive of all natural disasters. For
      decades, experts have been examining how flood losses can be mitigated. Just as
      in other risk domains, the study of risk perception and risk communication has
      gained increasing interest in flood risk management. Because of this research
      growth, a review of the state of the art in this domain is believed necessary.
      The review comprises 57 empirically based peer-reviewed articles on flood risk
      perception and communication from the Web of Science and Scopus databases. The
      characteristics of these articles are listed in a comprehensive table, presenting
      research design, research variables, and key findings. From this review, it
      follows that the majority of studies are of exploratory nature and have not
      applied any of the theoretical frameworks that are available in social science
      research. Consequently, a methodological standardization in measuring and
      analyzing people's flood risk perceptions and their adaptive behaviors is hardly
      present. This heterogeneity leads to difficulties in comparing results among
      studies. It is also shown that theoretical and empirical studies on flood risk
      communication are nearly nonexistent. The article concludes with a summary on
      methodological issues in the fields of flood-risk perception and flood-risk
      communication and proposes an agenda for future research.

PMID- 22651130
TI  - 'I never faced up to being gay': sexual, religious and ethnic identities among
      British Indian and British Pakistani gay men.
AB  - This paper presents the findings from a comparative qualitative study of British
      Indian and British Pakistani gay men, all of whom self-identified as members of
      their religious communities. Data were analysed using thematic analysis and
      identity process theory. Results suggest that the intersection between sexuality
      and religion is more relevant to British Pakistani participants, while the
      intersection between sexuality and ethnicity is more relevant to British Indian
      participants. For British Indian participants in particular, homosexuality seems
      to be socially problematic, posing potential obstacles for interpersonal and
      intergroup relations. Conversely, for British Pakistanis, homosexuality is both
      socially and psychologically problematic, affecting intrapsychic as well as
      interpersonal levels of human interdependence. Theoretical and practical
      implications are discussed.

PMID- 22651129
TI  - How changes in nutrition have influenced the development of allergic diseases in
      childhood.
AB  - The increasing prevalence of allergic diseases in childhood in the last decades
      could be linked to concomitant dietary changes, especially with the modified and
      lower consumption of fruit, vegetables and minerals. The consumption of these
      foods by pregnant women and children in the first years of life seems to be
      associated with a reduced risk of asthma and related symptoms. Foods that can
      prevent the development of wheezing through their antioxidant effects contain
      vitamin C and selenium; blood levels of these elements correlate negatively with
      the risk of wheezing. Intake of vitamin E during pregnancy also appears to be
      correlated with a reduced risk of wheezing for the unborn child. Similarly, low
      intake of zinc and carotenoids by pregnant women is associated with an increased
      risk of wheezing and asthma in childhood. Fiber also has anti-inflammatory
      properties and protective effects against allergic diseases such as atopic
      dermatitis and asthma. The consumption of fat influences the development of the
      airways. Populations in Western countries have increased their consumption of n-6
      PUFAs and, in parallel, reduced n-3 PUFAs. This has led to decreased production
      of PGE2, which is believed to have a protective effect against inflammation of
      the airways. Conflicting hypotheses also concern vitamin D; both an excess and a
      deficiency of vitamin D, in fact, have been associated with an increased risk of
      asthma. Further studies on the role of these substances are necessary before any
      conclusions can be drawn on a clinical level.

PMID- 22651131
TI  - Editorial comment to association of prostate-specific antigen doubling time and
      cancer in men undergoing repeat prostate biopsy.

PMID- 22651132
TI  - Was pulmonary vein isolation achieved?

PMID- 22651133
TI  - Computer simulation of the interactions of glyphosate with metal ions in phloem.
AB  - Essential nutrients such as trace metal ions, amino acids, and sugars are
      transported in the phloem from leaves to other parts of the plant. The major
      chelating agents in phloem include nicotianamine, histidine, cysteine, glutamic
      acid, and citrate. A computer model for the speciation of metal ions in phloem
      has been used to assess the degree to which the widely used herbicide glyphosate
      binds to Fe(3+), Fe(2+), Cu(2+), Zn(2+), Mn(2+), Ca(2+), and Mg(2+) in this fluid
      over the pH range of 8 to 6.5. The calculations show that glyphosate is largely
      unable to compete effectively with the biological chelating agents in phloem. At
      a typical phloem pH of 8, 1.5 mM glyphosate binds 8.4% of the total Fe(3+), 3.4%
      of the total Mn(2+), and 2.3% of the total Mg(2+) but has almost no effect on the
      speciation of Ca(2+), Cu(2+), Zn(2+), and Fe(2+). As the pH decreases to 6.5,
      there are some major shifts of the metal ions among the biological chelators, but
      only modest increases in glyphosate binding to 6% for Fe(2+) and 2% for Zn(2+).
      The calculations also indicate that over 90% of the glyphosate in phloem is not
      bound to any metal ion and that none of the metal-glyphosate complexes exceed
      their solubility limits.

PMID- 22651134
TI  - Knockdown of OY-TES-1 by RNAi causes cell cycle arrest and migration decrease in
      bone marrow-derived mesenchymal stem cells.
AB  - OY-TES-1 is a member of the CTA (cancer-testis antigen) group expressed in a
      variety of cancer and restrictedly expressed in adult normal tissues, except for
      testis. To determine whether MSCs (mesenchymal stem cells) express OY-TES-1 and
      its possible roles on MSCs, OY-TES-1 expression in MSCs isolated from human bone
      marrow was tested with RT (reverse transcription)-PCR, immunocytochemistry and
      Western blot. Using RNAi (RNA interference) technology, OY-TES-1 expression was
      knocked down followed by analysing cell viability, cell cycle, apoptosis and
      migration ability. MSCs expressed OY-TES-1 at both mRNA and protein levels. The
      down-regulation of OY-TES-1 expression in these MSCs caused cell growth
      inhibition, cell cycle arrest, apoptosis induction and migration ability
      attenuation. Through these primary results it was suggested that OY-TES-1 may
      influence the biological behaviour of MSCs.

PMID- 22651135
TI  - Fabrication of a form- and size-variable microcellular-polymer-stabilized metal
      nanocomposite using supercritical foaming and impregnation for catalytic
      hydrogenation.
AB  - This article presents the fabrication of size-controllable and shape-flexible
      microcellular high-density polyethylene-stabilized palladium nanoparticles (Pd/m
      HDPE) using supercritical foaming, followed by supercritical impregnation. These
      nanomaterials are investigated for use as heterogeneous hydrogenation catalysts
      of biphenyls in supercritical carbon dioxide with no significant surface and
      inner mass transfer resistance. The morphology of the Pd/m-HDPE is examined using
      scanning electron microscopy images of the pores inside Pd/m-HDPE catalysts and
      transmission electron microscopy images of the Pd particles confined in an HDPE
      structure. This nanocomposite simplifies industrial design and operation. These
      Pd/m-HDPE catalysts can be recycled easily and reused without complex recovery
      and cleaning procedures.

PMID- 22651136
TI  - Reply to: Graefe-Mody U, Friedrich C, Port A et al. Effect of renal impairment on
      the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin.
      Diabetes Obes Metab 2011; 13: 939-946.

PMID- 22651217
TI  - Transition-metal-catalyzed enantioselective heteroatom-hydrogen bond insertion
      reactions.
AB  - Carbon-heteroatom bonds (C-X) are ubiquitous and are among the most reactive
      components of organic compounds. Therefore investigations of the construction of
      C-X bonds are fundamental and vibrant fields in organic chemistry. Transition
      metal-catalyzed heteroatom-hydrogen bond (X-H) insertions via a metal carbene or
      carbenoid intermediate represent one of the most efficient approaches to form C-X
      bonds. Because of the availability of substrates, neutral and mild reaction
      conditions, and high reactivity of these transformations, researchers have widely
      applied transition-metal-catalyzed X-H insertions in organic synthesis.
      Researchers have developed a variety of rhodium-catalyzed asymmetric C-H
      insertion reactions with high to excellent enantioselectivities for a wide range
      of substrates. However, at the time that we launched our research, very few
      highly enantioselective X-H insertions had been documented primarily because of a
      lack of efficient chiral catalysts and indistinct insertion mechanisms.  In this
      Account, we describe our recent studies of copper- and iron-catalyzed asymmetric
      X-H insertion reactions by using chiral spiro-bisoxazoline and diimine ligands.
      The copper complexes of chiral spiro-bisoxazoline ligands proved to be highly
      enantioselective catalysts for N-H insertions of alpha-diazoesters into anilines,
      O-H insertions of alpha-diazoesters into phenols and water, O-H insertions of
      alpha-diazophosphonates into alcohols, and S-H insertions of alpha-diazoesters
      into mercaptans. The iron complexes of chiral spiro-bisoxazoline ligands afforded
      the O-H insertion of alpha-diazoesters into alcohols and water with unprecedented
      enantioselectivities. The copper complexes of chiral spiro-diimine ligands
      exhibited excellent reactivity and enantioselectivity in the Si-H insertion of
      alpha-diazoacetates into a wide range of silanes. These transition-metal
      catalyzed X-H insertions have many potential applications in organic synthesis
      because the insertion products, including chiral alpha-aminoesters, alpha
      hydroxyesters, alpha-hydroxyphosphonates, alpha-mercaptoesters, and alpha-silyl
      esters, are important building blocks for the synthesis of biologically active
      compounds.  The electronic properties of alpha-diazoesters and anilines markedly
      affected the enantioselectivity of N-H insertion reaction, which supports a
      stepwise ylide insertion mechanism. A novel binuclear spiro copper complex was
      isolated and fully characterized using X-ray diffraction analysis and ESI-MS
      analysis. The positive nonlinear effect indicated that binuclear copper complexes
      were the catalytically active species. The 14-electron copper centers, trans
      coordination model, perfect C(2)-symmetric chiral pocket, and Cu-Cu interaction
      facilitate the performance of the chiral spiro catalysts in X-H insertion
      reactions.

PMID- 22651218
TI  - Ethanol effects on apparent solubility of poorly soluble drugs in simulated
      intestinal fluid.
AB  - Ethanol intake can lead to an unexpected and possibly problematic increase in the
      bioavailability of druglike compounds. In this work we investigated the effect of
      ethanol on the apparent solubility and dissolution rate of poorly soluble
      compounds in simulated intestinal fluid representing a preprandial state. A
      series of 22 structurally diverse, poorly soluble compounds were measured for
      apparent solubility and intrinsic dissolution rate (37  degrees C) in phosphate
      buffer pH 6.5 (PhB6.5) and fasted state simulated intestinal fluid (FaSSIF, pH
      6.5) with and without ethanol at 5% v/v or 20% v/v. The obtained data were used
      to understand for which molecules ethanol results in an increased apparent
      solubility and, therefore, may increase the amount of drug absorbed. In
      FaSSIF20%ethanol 59% of the compounds displayed >3-fold higher apparent
      solubility than in pure FaSSIF, whereas the effects of 5% ethanol on solubility,
      in most cases, were negligible. Acidic and neutral compounds were more
      solubilized by the addition of ethanol than by lecithin/taurocholate aggregates,
      whereas bases showed a more substance-specific response to the additives in the
      buffer. The stronger solubilizing capacity of ethanol as compared to the mixed
      lipid aggregates in FaSSIF was further identified through Spearman rank analyses,
      which showed a stronger relationship between FaSSIF20%ethanol and
      PhB6.5,20%ethanol (rS of 0.97) than FaSSIF20%ethanol and FaSSIF (rS of 0.86). No
      relationships were found between solubility changes in media containing ethanol
      and single physicochemical properties, but multivariate data analysis showed that
      inclusion of ethanol significantly reduced the negative effect of compound
      lipophilicity on solubility. For this data set the higher concentration of
      ethanol gave a dose number (Do) <1 for 30% of the compounds that showed
      incomplete dissolution in FaSSIF. Significant differences were shown in the
      melting point, lipophilicity, and dose profiles between the compounds having a Do
      < 1 and Do > 1, with the latter having higher absolute values in all three
      parameters. In conclusion, this study showed that significant effects of ethanol
      on apparent solubility in the preprandial state can be expected for lipophilic
      compounds. The results herein indicate that acidic and neutral compounds are more
      sensitive to the addition of ethanol than to the mixed lipid aggregates present
      in the fasted intestine. 

PMID- 22651219
TI  - Photoinduced charge transfer in short-distance ferrocenylsubphthalocyanine dyads.
AB  - Two new ferrocenylsubphthalocyanine dyads with ferrocenylmethoxide (2) and
      ferrocenecarboxylate (3) substituents directly attached to the subphthalocyanine
      ligand via the axial position have been prepared and characterized using NMR, UV
      vis, and magnetic circular dichroism (MCD) spectroscopies as well as X-ray
      crystallography. The redox properties of the ferrocenyl-containing dyads 2 and 3
      were investigated using the cyclic voltammetry (CV) approach and compared to
      those of the parent subphthalocyanine 1. CV data reveal that the first reversible
      oxidation is ferrocene-centered, while the second oxidation and the first
      reduction are localized on the subphthalocyanine ligand. The electronic
      structures and nature of the optical bands observed in the UV-vis and MCD spectra
      of all target compounds were investigated by a density functional theory
      polarized continuum model (DFT-PCM) and time-dependent (TD)DFT-PCM approaches. It
      has been found that in both dyads the highest occupied molecular orbital (HOMO)
      to HOMO-2 are ferrocene-centered molecular orbitals, while HOMO-3 as well as
      lowest unoccupied molecular orbital (LUMO) and LUMO+1 are localized on the
      subphthalocyanine ligand. TDDFT-PCM data on complexes 1-3 are consistent with the
      experimental observations, which indicate the dominance of pi-pi* transitions in
      the UV-vis spectra of 1-3. The excited-state dynamics of the dyads 2 and 3 were
      investigated using time-correlated single photon counting, which indicates that
      fluorescence quenching is more efficient in dyad 3 compared to dyad 2. These
      fluorescence lifetime measurements were interpreted on the basis of DFT-PCM
      calculations.

PMID- 22651220
TI  - Thermal aromatizations of 2-vinylmethylenecyclopropane and 3-vinylcyclobutene.
AB  - A comprehensive theoretical investigation of thermal rearrangements of 2
      vinylmethylenecyclopropane and 3-vinylcyclobutene is carried out employing
      density functional theory and high level ab initio methods, such as the complete
      active space self-consistent field, multi-reference second-order Moller-Plesset
      perturbation theory, and coupled-cluster singles and doubles with perturbative
      triples. In all computations, Pople's polarized triple-zeta split valence basis
      set, 6-311G(d,p), is utilized. The potential energy surface for the relevant
      system is explored to provide theoretical insights for the thermal aromatizations
      of 2-vinylmethylenecyclopropane and 3-vinylcyclobutene. The rate constant for
      each isomerization reaction is computed using the transition state theory. The
      simultaneous first-order ordinary-differential equations are solved numerically
      for the considered system to obtain time-dependent concentrations, hence the
      product distributions at a given temperature. Our results demonstrate that at
      high temperatures thermal aromatizations of 2-vinylmethylenecyclopropane (at 700 
      degrees C and higher) and 3-vinylcyclobutene (at 500  degrees C and higher) are
      feasible under appropriate experimental conditions. However, at low temperatures
      (at 500  degrees C and lower), 2-vinylmethylenecyclopropane yields 3
      methylenecyclopentene as a unique product, kinetically, and the formation of
      benzene is not favorable. Similarly, at 300  degrees C and lower temperatures, 3
      vinylcyclobutene can only yield trans-1,3,5-hexatriene (major) and cis-1,3,5
      hexatriene (minor). At 300 < T < 500  degrees C, 3-vinylcyclobutene almost
      completely yields 1,3-cyclohexadiene. Hence, our computations provide a useful
      insight for the synthesis of substituted aromatic compounds. Further, calculated
      energy values (reaction energies and activation parameters) are in satisfactory
      agreement with the available experimental results.

PMID- 22651221
TI  - Measurement of implementation components ten years after a nationwide
      introduction of empirically supported programs--a pilot study.
AB  - BACKGROUND: Ten years after the nationwide dissemination of two evidence-based
      treatment programs, the status of the implementation components was evaluated in
      a cross-sectional study. The aim of the study was to pilot a standardized measure
      of implementation components by examining the factor structure, the reliabilities
      of the scores, and their association with implementation outcome variables. The
      aim was also to compare implementation profiles of the two evidence-based
      programs based on multi informant assessments. METHODS: The 218 participants in
      the study were therapists, supervisors, and agency leaders working with Parent
      Management Training, the Oregon model (PMTO), and Multisystemic Therapy (MST) in
      Norway. Interviewers filled in an electronic version of the Implementation
      Components Questionnaire during a telephone interview. RESULTS: The factor
      analysis of the eight one-dimensional subscales resulted in an individual
      clinical-level factor and an organizational system-level factor. Age, experience,
      and number of colleagues in the workplace were negatively correlated with
      positive ratings of the implementation process, but the number of colleagues
      working with the same program predicted positive ratings. MST and PMTO had
      different implementation profiles and therapists, supervisors, and managers
      evaluated some of the implementation drivers significantly differently.
      CONCLUSIONS: The psychometric quality of the questionnaire was supported by
      measures of internal consistency, factor analyses of the implementation
      components, and the comparisons of implementation profiles between programs and
      respondent groups. A moderate, but consistent association in the expected
      direction was found with the implementation outcome variables.

PMID- 22651222
TI  - Time-weighted average sampling of airborne propylene glycol ethers by a solid
      phase microextraction device.
AB  - A solid-phase microextraction (SPME) device was used as a diffusive sampler for
      airborne propylene glycol ethers (PGEs), including propylene glycol monomethyl
      ether (PGME), propylene glycol monomethyl ether acetate (PGMEA), and dipropylene
      glycol monomethyl ether (DPGME). Carboxen-polydimethylsiloxane (CAR/PDMS) SPME
      fiber was selected for this study. A polytetrafluoroethylene (PTFE) tubing was
      used as the holder, and the SPME fiber assembly was inserted into the tubing as a
      diffusive sampler. The diffusion path length and area of the sampler were 0.3 cm
      and 0.00086 cm(2), respectively. The theoretical sampling constants at 30 degrees
      C and 1 atm for PGME, PGMEA, and DPGME were 1.50 * 10(-2), 1.23 * 10(-2) and 1.14
      * 10(-2) cm(3) min(-1), respectively. For evaluations, known concentrations of
      PGEs around the threshold limit values/time-weighted average with specific
      relative humidities (10% and 80%) were generated both by the air bag method and
      the dynamic generation system, while 15, 30, 60, 120, and 240 min were selected
      as the time periods for vapor exposures. Comparisons of the SPME diffusive
      sampling method to Occupational Safety and Health Administration (OSHA) organic
      Method 99 were performed side-by-side in an exposure chamber at 30 degrees C for
      PGME. A gas chromatography/flame ionization detector (GC/FID) was used for sample
      analysis. The experimental sampling constants of the sampler at 30 degrees C were
      (6.93 +/- 0.12) * 10(-1), (4.72 +/- 0.03) * 10(-1), and (3.29 +/- 0.20) * 10(-1)
      cm(3) min(-1) for PGME, PGMEA, and DPGME, respectively. The adsorption of
      chemicals on the stainless steel needle of the SPME fiber was suspected to be one
      of the reasons why significant differences between theoretical and experimental
      sampling rates were observed. Correlations between the results for PGME from both
      SPME device and OSHA organic Method 99 were linear (r = 0.9984) and consistent
      (slope = 0.97 +/- 0.03). Face velocity (0-0.18 m/s) also proved to have no
      effects on the sampler. However, the effects of temperature and humidity have
      been observed. Therefore, adjustments of experimental sampling constants at
      different environmental conditions will be necessary.

PMID- 22651223
TI  - Drug-induced interstitial lung disease: mechanisms and best diagnostic
      approaches.
AB  - Drug-induced interstitial lung disease (DILD) is not uncommon and has many
      clinical patterns, ranging from benign infiltrates to life-threatening acute
      respiratory distress syndrome. There are two mechanisms involved in DILD, which
      are probably interdependent: one is direct, dose-dependent toxicity and the other
      is immune-mediated. Cytotoxic lung injury may result from direct injury to
      pneumocytes or the alveolar capillary endothelium. Drugs can induce all types of
      immunological reactions described by Gell and Coombs; however, most reactions in
      immune-mediated DILD may be T cell-mediated. DILD can be difficult to diagnose;
      diagnosis is often possible by exclusion alone. Identifying the causative drug
      that induces an allergy or cytotoxicity is essential for preventing secondary
      reactions. One method to confirm the diagnosis of a drug-induced disease is re
      exposure or re-test of the drug. However, clinicians are reluctant to place
      patients at further risk of illness, particularly in cases with severe drug
      induced diseases. Assessment of cell-mediated immunity has recently increased,
      because verifying the presence or absence of drug-sensitized lymphocytes can aid
      in confirmation of drug-induced disease. Using peripheral blood samples from drug
      allergic patients, the drug-induced lymphocyte stimulation test (DLST) and the
      leukocyte migration test (LMT) can detect the presence of drug-sensitized T
      cells. However, these tests do not have a definite role in the diagnosis of DILD.
      This study explores the potential of these new tests and other similar tests in
      the diagnosis of DILD and provides a review of the relevant literature on this
      topic.

PMID- 22651224
TI  - CORNET 2.0: integrating plant coexpression, protein-protein interactions,
      regulatory interactions, gene associations and functional annotations.
AB  - To enable easy access and interpretation of heterogeneous and scattered data, we
      have developed a user-friendly tool for data mining and integration in
      Arabidopsis, named CORNET. This tool allows the browsing of microarray data, the
      construction of coexpression and protein-protein interaction (PPI) networks and
      the exploration of diverse functional annotations. Here, we present the new
      functionalities of CORNET 2.0 for data integration in plants. First of all,
      CORNET allows the integration of regulatory interaction datasets accessible
      through the new transcription factor (TF) tool that can be used in combination
      with the coexpression tool or the PPI tool. In addition, we have extended the PPI
      tool to enable the analysis of gene-gene associations from AraNet as well as
      newly identified PPIs. Different search options are implemented to enable the
      construction of networks centered around multiple input genes or proteins. New
      functional annotation resources are included to retrieve relevant literature,
      phenotypes, plant ontology and biological pathways. We have also extended CORNET
      to attain the construction of coexpression and PPI networks in the crop species
      maize. Networks and associated evidence of the majority of currently available
      data types are visualized in Cytoscape. CORNET is available at
      https://bioinformatics.psb.ugent.be/cornet.

PMID- 22651225
TI  - Determinants of high-sensitivity cardiac troponin T during acute exacerbation of
      chronic obstructive pulmonary disease: a prospective cohort study.
AB  - BACKGROUND: A high-sensitivity cardiac troponin T (hs-cTnT) concentration above
      the 99th percentile (i.e. 14 ng/L) is common during Acute Exacerbation of Chronic
      Obstructive Pulmonary Disease (AECOPD) and associated with increased mortality.
      The objective of the study was to identify factors associated with hs-cTnT levels
      during AECOPD. METHODS: We included 99 patients with AECOPD on admission. As 41
      patients had one or more repeat admissions, there were 202 observations in the
      final analysis. We recorded clinical and biochemical data, medication,
      spirometry, chest radiographs, and ECGs. The data were analysed for cross
      sectional and longitudinal associations using ordinary least square as well as
      linear mixed models with the natural logarithm of hs-cTnT as the dependent
      variable. RESULTS: Mean age at inclusion was 71.5 years, mean FEV1/FVC was 45%,
      and median hs-cTnT was 27.0 ng/L. In a multivariable model there was a 24%
      increase in hs-cTnT per 10 years increase in age (p < 0.0001), a 6% increase per
      10 MUmol/L increase in creatinine (p = 0.037), and a 2% increase per month after
      enrollment (p = 0.046). Similarly, the ratios of hs-cTnT between patients with
      and without tachycardia (heart rate >=100/min) and with and without history of
      arterial hypertension were 1.25 (p = 0.042) and 1.44 (p = 0.034), respectively.
      We found no significant association between arterial hypoxemia and elevated hs
      cTnT. CONCLUSION: Age, arterial hypertension, tachycardia, and serum creatinine
      are independently associated with the level of hs-cTnT on admission for AECOPD.

PMID- 22651226
TI  - Serratustones A and B representing a new dimerization pattern of two types of
      sesquiterpenoids from Chloranthus serratus.
AB  - Serratustones A (1) and B (2), featuring a new carbon skeleton and representing a
      novel dimerization pattern of two different types of sesquiterpenoids, were
      isolated from Chloranthus serratus. Their structures with absolute configuration
      were determined on the basis of a detailed explanation of spectroscopic data, X
      ray crystallography, and CD analysis in combination with ECD calculation.

PMID- 22651227
TI  - Eumelanin buildup on the nanoscale: aggregate growth/assembly and visible
      absorption development in biomimetic 5,6-dihydroxyindole polymerization.
AB  - Establishing structure-property relationships in the black insoluble eumelanins,
      the key determinants of human pigmentation and skin photoprotective system, is a
      considerable conceptual and experimental challenge in the current drive for
      elucidation of the biological roles of these biopolymers and their application as
      advanced materials for organoelectronics. Herein, we report a new breakthrough
      toward this goal by the first detailed investigation on the nanoscale level of
      the oxidative polymerization of 5,6-dihydroxyindole (DHI), a model process of
      eumelanin synthesis. On the basis of a combined use of spectrophotometry, dynamic
      light scattering (DLS), and small-angle neutron scattering (SANS) investigations,
      it was possible to unveil the dynamics of the aggregation process before
      precipitation, the key relationships with visible light absorption and the shape
      of fundamental aggregates. The results indicated a polymerization mechanism of
      the type: Polymer(n) + DHI(x) = Polymer(n+x), where DHI(x) indicates monomer,
      dimer, or low oligomers (x <= 5). During polymerization, visible absorption
      increases rapidly, reaching a plateau. Particle growth proceeds slowly, with
      formation of 2-D structures ~55 nm thick, until precipitation occurs, that is,
      when large aggregates with a maximum hydrodynamic radius (R(h)) of ~1200 nm are
      formed. Notably, markedly smaller R(h) values, up to ~110 nm, were determined in
      the presence of poly(vinyl alcohol) (PVA) that was shown to be an efficient
      aggregation-preventing agent for polymerizing DHI ensuring water solubilization.
      Finally, it is shown that DHI monomer can be efficiently and partially
      irreversibly depleted from aqueous solutions by the addition of eumelanin
      suspensions. This behavior is suggested to reflect oxidant-independent competing
      pathways of polymer synthesis and buildup via monomer conversion on the active
      aggregate surface contributing to particle growth. Besides filling crucial gaps
      in DHI polymerization, these results support the attractive hypothesis that
      eumelanins may behave as a peculiar example of living biopolymers. The potential
      of PVA as a powerful tool for solution chemistry-based investigations of
      eumelanin supramolecular organization and for technological manipulation purposes
      is underscored.

PMID- 22651228
TI  - Inclusion compound based approach to arrays of artificial dipolar molecular
      rotors. A surface inclusion.
AB  - We describe an approach to regular triangular arrays of dipolar molecular rotors
      based on insertion of dipolar rotator carrying shafts as guests into channels of
      a host, tris(o-phenylenedioxy)cyclotriphosphazene (TPP). The rotor guests can
      either enter the bulk of the host or stay at or near the surface, if a suitable
      stopper is installed at the end of the shaft. Differential scanning calorimetry,
      solid-state NMR, and powder X-ray diffraction were used to examine the insertion
      of a dipolar rotor synthesized for the purpose, 1-n-hexadecyl-12-(2,3
      dichlorophenyl)-p-dicarba-closo-dodecaborane, and it was found that it forms a
      surface inclusion compound. Rotational barriers from 1.2 to 9 kcal/mol were found
      by dielectric spectroscopy and were attributed to rotors inserted into the
      surface to different degrees, some rubbing the surface as they turn.

PMID- 22651229
TI  - Editorial comment to therapy management of cardiovascular adverse events in the
      context of targeted therapy for metastatic renal cell carcinoma.

PMID- 22651230
TI  - Sequence variability in three mitochondrial genes between the two pig nodule
      worms Oesophagostomum dentatum and O. quadrispinulatum.
AB  - In this study, sequence variation in three mitochondrial DNA regions, namely
      cytochrome c oxidase subunit (cox1) and NADH dehydrogenase subunits 1 and 4 (nad1
      and nad4), between Oesophagostomum dentatum and O. quadrispinulatum isolated from
      pigs in different geographical origins in Mainland China was examined, and their
      phylogenetic relationships were reconstructed. A partial of the cox1 (pcox1),
      nad1, and nad4 genes (pnad1 and pnad4) were amplified separately from individual
      nodule worms by PCR and were subjected to direct sequencing in order to define
      sequence variations. While the intraspecific sequence variations within each of
      the two species were 0.3-5.2% for pcox1, 0-4.9% for pnad1, and 0-7.1% for pnad4,
      the interspecific sequence differences were significantly higher, being 10.7
      13.4% for pcox1, 11-14.6% for pnad1, and 14.9-18% for pnad4, respectively. There
      were a number of nucleotide positions in the pcox1, pnad1, and pnad4 sequences
      with no apparent intraspecific variation but distinct interspecific differences
      among those samples of Oesophagostomum spp. examined, which may be used as
      genetic makers for the identification and differentiation of the Oesophagostomum
      spp. Phylogenetic analyses using three inference methods, namely Bayesian
      inference, maximum likelihood, and maximum parsimony based on the combined
      sequences of pcox1, pnad1, and pnad4 revealed that the O. dentatum and O.
      quadrispinulatum form monophyletic groups, respectively. These findings
      demonstrated clearly the usefulness of the three mitochondrial sequences for
      studying systematics, population genetic structures, and the molecular ecology of
      Oesophagostomum spp.

PMID- 22651231
TI  - Molecular characteristics of mitochondrial DNA and phylogenetic analysis of the
      loach (Misgurnus anguillicaudatus) from the Poyang Lake.
AB  - The goal of our study was to investigate the molecular characteristics of
      mitochondrial DNA (mtDNA) and phylogenetic construction of the weather loach
      (Misgurnus anguillicaudatus) in Poyang Lake. The complete mitochondrial genome
      was 16,634 bp, and the gene order was identical to that of teleost fishes.
      Compared with the previous reported weather loach in China, there were numerous
      nucleotide substitutions and length polymorphisms on the structural genes of
      mitochondrial DNA in the loach from the Poyang Lake. The Phylogenetic tree
      indicated that the loach had its own molecular characteristics and was somewhat
      different from those in other regions of China. Fourteen unique haplotypes of the
      cytochrome b (cyt b) gene were obtained from 300 weather loaches. The
      Phylogenetic tree based on the cyt b gene showed that the loaches were
      substructured into two different populations in The Poyang Lake. Results
      indicated that the loaches in Poyang Lake not only showed the same phylogeny as
      the loaches in other areas of China, but also generated its own unique
      phylogenetic relationships.

PMID- 22651232
TI  - Interspecific variation in mitochondrial serine transfer RNA (UCN) in Euptychiina
      butterflies (Lepidoptera: Satyrinae): structure and alignment.
AB  - The nucleotide variation and structural patterns of mitochondrial RNA molecule
      have been proposed as useful tools in molecular systematics; however, their
      usefulness is always subject to a proper assessment of homology in the sequence
      alignment. The present study describes the secondary structure of mitochondrial
      tRNA for the amino acid serine (UCN) on 13 Euptychiina species and the evaluation
      of its potential use for evolutionary studies in this group of butterflies. The
      secondary structure of tRNAs showed variation among the included species except
      between Hermeuptychia sp1 and sp2. Variation was concentrated in the ribotimidina
      pseudouridine-cystosine (TpsiC), dihydrouridine (DHU) and variable loops and in
      the DHU and TpsiC arms. These results suggest this region as a potential marker
      useful for taxonomic differentiation of species in this group and also confirm
      the importance of including information from the secondary structure of tRNA to
      optimize the alignments.

PMID- 22651233
TI  - Population genetic structure of Scombrops boops (Percoid, Scombropidae) around
      the Japanese archipelago inferred from the cytochrome b gene sequence in
      mitochondrial DNA.
AB  - The gnomefish (Scombrops boops) is a member of the percoid family Scombropidae,
      which includes a single genus and three to four species worldwide. Since little
      is known about the ecology of this species, here, sequencing analysis of the
      cytochrome b gene (1141 bp) in mitochondrial DNA detected 101 haplotypes from 186
      individuals of S. boops collected from waters at seven localities around the
      Japanese archipelago. A single haplotype (Sb2) was the most abundant in the
      combined populations of S. boops from various localities. Genetic population
      structure analyses revealed no significant differences among these populations
      (Fst = - 0.0313-0.0195; Phist = - 0.0505-0.0615) with high haplotype diversity
      and low nucleotide diversity. This suggests that S. boops around the Japanese
      archipelago constitutes a single population, and indicates that the genetic
      structure of this population may be influenced by larval and egg dispersal in
      association with warm currents.

PMID- 22651234
TI  - Conservation genetics of harvested river turtles, Podocnemis expansa and
      Podocnemis unifilis, in the Peruvian Amazon: all roads lead to Iquitos.
AB  - We present a mtDNA analysis of Podocnemis expansa (n = 81) and Podocnemis
      unifilis (n = 228) turtles traded in Peru to evaluate the potential origin of
      these animals. In particular, we were interested in the relationship between
      samples reported in the Iquitos markets (IMs) and a Pacaya Samiria Natural
      Reserve (PSNR) where illegal hunting is presumed. Our mtDNA data showed that, for
      both species, all haplotypes found within the PSNR were observed in the IM, and
      that these markets also displayed haplotypes not documented in the reserve. This
      suggests that the IMs are recipients of Podocnemis turtles from within and
      outside the PSNR. The fact that most of the haplotype diversity observed in the
      markets was not found within the PSNR strongly suggests that Podocnemis genetic
      diversity is exploited in areas where conservation actions are limited. Hence, we
      recommend expanding Podocnemis conservation efforts outside of protected areas.

PMID- 22651235
TI  - Morphological taxonomy and molecular divergence of four balitorid species
      (subfamily: Nemachelinae) from Central Himalaya, India.
AB  - The fishes in this study belong to the difficult group. It is difficult to
      identify about more than 50 nemacheilid loach species in India, mainly due to the
      poor quality of the original descriptions, the lack of good reviews, and the
      similarity of a number of the banded species. In view of this, a morphometric and
      genetic study was conducted on four species that have been documented in Central
      Himalayan region of India. Using comparative methods, a contribution to the
      knowledge about the variability of four Himalayan hillstream loaches, a molted
      loach Acanthocobitis botia (Hamilton, 1822), Nemacheilus corica (Hamilton, 1822),
      a creek loach Schistura beavani (Gunther, 1868), and Schistura montana
      (McClelland, 1838), was accomplished. Morphometric data were analyzed by
      univariate (CV and analysis of variance) and multivariate analyses (discriminant
      function analysis and cluster analysis). Based on the results of these
      statistical analyses, generally all four species grouped into their own species
      cluster with minimal overlap between two species of genus Schistura.
      Mitochondrial DNA cytochrome b (Cyt b) gene analysis revealed 7.7-17.6% genetic
      distances among the four species. Molecular phylogenetic relationship among these
      species and other Balitoridae species was investigated using published
      mitochondrial Cyt b sequences. Dendrograms obtained by the maximum likelihood and
      maximum parsimony method analyses exhibited the same topology. According to this
      topology, all the four species represented distinct species group and A. botia
      form the most distinct species while S. beavani and S. montana are clustered
      together with Nemacheilus species to form a single group. This work may build the
      base for the revision of taxonomic identity of fishes of the family Balitoridae.
      The results may further help to enhance the knowledge of the ichthyologists in
      understanding the fish fauna of India and assist them in planning conservation
      and management strategies for the propagation of these less studied small
      indigenous species along their natural range of distribution.

PMID- 22651236
TI  - Bacterial phylogenetic tree construction based on genomic translation stop
      signals.
AB  - BACKGROUND: The efficiencies of the stop codons TAA, TAG, and TGA in protein
      synthesis termination are not the same. These variations could allow many genes
      to be regulated. There are many similar nucleotide trimers found on the second
      and third reading-frames of a gene. They are called premature stop codons (PSC).
      Like stop codons, the PSC in bacterial genomes are also highly bias in terms of
      their quantities and qualities on the genes. Phylogenetically related species
      often share a similar PSC profile. We want to know whether the selective forces
      that influence the stop codons and the PSC usage biases in a genome are related.
      We also wish to know how strong these trimers in a genome are related to the
      natural history of the bacterium. Knowing these relations may provide better
      knowledge in the phylogeny of bacteria RESULTS: A 16SrRNA-alignment tree of 19
      well-studied alpha-, beta- and gamma-Proteobacteria Type species is used as
      standard reference for bacterial phylogeny. The genomes of sixty-one bacteria,
      belonging to the alpha-, beta- and gamma-Proteobacteria subphyla, are used for
      this study. The stop codons and PSC are collectively termed "Translation Stop
      Signals" (TSS). A gene is represented by nine scalars corresponding to the
      numbers of counts of TAA, TAG, and TGA on each of the three reading-frames of
      that gene. "Translation Stop Signals Ratio" (TSSR) is the ratio between the TSS
      counts. Four types of TSSR are investigated. The TSSR-1, TSSR-2 and TSSR-3 are
      each a 3-scalar series corresponding respectively to the average ratio of TAA:
      TAG: TGA on the first, second, and third reading-frames of all genes in a genome.
      The Genomic-TSSR is a 9-scalar series representing the ratio of distribution of
      all TSS on the three reading-frames of all genes in a genome. Results show that
      bacteria grouped by their similarities based on TSSR-1, TSSR-2, or TSSR-3 values
      could only partially resolve the phylogeny of the species. However, grouping
      bacteria based on thier Genomic-TSSR values resulted in clusters of bacteria
      identical to those bacterial clusters of the reference tree. Unlike the 16SrRNA
      method, the Genomic-TSSR tree is also able to separate closely related
      species/strains at high resolution. Species and strains separated by the Genomic
      TSSR grouping method are often in good agreement with those classified by other
      taxonomic methods. Correspondence analysis of individual genes shows that most
      genes in a bacterial genome share a similar TSSR value. However, within a
      chromosome, the Genic-TSSR values of genes near the replication origin region
      (Ori) are more similar to each other than those genes near the terminus region
      (Ter). CONCLUSION: The translation stop signals on the three reading-frames of
      the genes on a bacterial genome are interrelated, possibly due to frequent off
      frame recombination facilitated by translational-associated recombination (TSR).
      However, TSR may not occur randomly in a bacterial chromosome. Genes near the Ori
      region are often highly expressed and a bacterium always maintains multiple
      copies of Ori. Frequent collisions between DNA- polymerase and RNA-polymerase
      would create many DNA strand-breaks on the genes; whereas DNA strand-break
      induced homologues-recombination is more likely to take place between genes with
      similar sequence. Thus, localized recombination could explain why the TSSR of
      genes near the Ori region are more similar to each other. The quantity and
      quality of these TSS in a genome strongly reflect the natural history of a
      bacterium. We propose that the Genomic- TSSR can be used as a subjective
      biomarker to represent the phyletic status of a bacterium.

PMID- 22651237
TI  - Oxidative status of stressed Caenorhabditis elegans treated with epicatechin.
AB  - The aim of this work was to examine the mechanisms involved in the in vivo
      antioxidant effects of epicatechin (EC), a major flavonoid in the human diet. The
      influence of EC in different oxidative biomarkers (reactive oxygen species (ROS)
      production, intracellular glutathione, activity of catalase (CAT), glutathione
      peroxidase (GPx), and superoxide dismutase (SOD)) was studied in the model
      organism  Caenorhabditis elegans . Under thermal stress condition, exposure of
      the worms (wild type N2 strains) to EC (200 MUM) significantly reduced ROS levels
      (up to 28%) and enhanced the production of reduced glutathione (GSH). However, no
      significant changes were appreciated in the activities of GPx, CAT, and SOD,
      suggesting that further activation of these antioxidant enzymes was not required
      once the concentration of ROS in the EC-treated worms was restored to what could
      be considered physiological levels.

PMID- 22651239
TI  - Implantation feasibility, procedure-related adverse events and lead performance
      during 1-year follow-up in patients undergoing triple-site cardiac
      resynchronization therapy: a substudy of TRUST CRT randomized trial.
AB  - INTRODUCTION: This substudy was to assess implantation feasibility and long-term
      safety of triple-site resynchronization therapy (CRT) in a series of consecutive
      patients included in a randomized trial. METHODS AND RESULTS: One hundred
      consecutive patients enrolled into Triple-Site Versus Standard Cardiac
      Resynchronization Therapy Randomized Trial were analyzed. Eligibility criteria
      included NYHA class III-IV, sinus rhythm, QRS >= 120 milliseconds, left
      ventricular ejection fraction <=35%, and significant mechanical dyssynchrony.
      Patients were randomized in a 1:1 ratio to conventional or triple-site CRT with
      defibrillator-cardioverter. After 12 months of resynchronization 30% of patients
      with conventional resynchronization and 12.5% with triple-site CRT were in NYHA
      functional class III or IV (P < 0.05). Implantation of triple-site systems was
      significantly longer (median 125 minutes vs 96 minutes; P < 0.001), with higher
      fluoroscopic exposure, especially in patients with very enlarged left ventricle
      or pulmonary hypertension. Implantation success-rate was similar in the triple
      site and conventional group (94% vs 98%; P = NS); however, additional techniques
      had to be used in a greater proportion of the triple-site patients (33.3% vs 16%;
      P < 0.05). Long-term lead performance tests revealed significantly higher pacing
      threshold and lower impedance in the triple-site group. The 1-year incidence of
      serious, CRT-related adverse events was similar in triple-site and conventional
      group (20.8% vs 30%; P = NS). CONCLUSIONS: Triple-site CRT is associated with
      more pronounced functional improvement than standard resynchronization. This form
      of pacing is equally safe and feasible as the conventional CRT. However, triple
      site procedure is more time-consuming, associated with higher radiation exposure
      and the need to use additional techniques. Triple-site resynchronization is
      associated with less favorable electrical lead characteristics.

PMID- 22651240
TI  - nPIV velocity measurement of nanofluids in the near-wall region of a
      microchannel.
AB  - Colloidal suspensions of nano-sized particles in a base fluid, nanofluids, have
      recently gained popularity as cooling fluids mainly due to their enhanced heat
      transfer capabilities. However, there is controversy in the literature on the
      reported properties of nanofluids and their applicability, especially since there
      is no fundamental understanding that explains these enhancements. A better
      understanding of these fluids and how they interact with a solid boundary may be
      achieved by a detailed near-wall fluid flow study at nanoscale. This work
      presents for the first time the near-wall velocity measurements for nanofluids
      using nanoparticle image velocimetry. This novel technique uses evanescent
      illumination in the solid-fluid interface to measure near-wall velocity field
      with an out-of-plane resolution on the order of O(100 nm). Nanofluids of
      different concentrations were prepared by dispersing silicon dioxide particles
      (10 to 20 nm) in water as the base fluid. Initially, viscosity measurements were
      conducted for the prepared nanofluids. The near-wall velocity data were then
      measured and compared with that of the base fluid at the same flow condition. It
      was observed that even though nanofluid viscosity had increased with particle
      loading, the near-wall velocity values were similar to that of the base fluid for
      a given flow rate. Together, these measurements vindicate the homogenous and
      Newtonian characteristics of the nanofluids in the near-wall region. Despite the
      low particle concentrations investigated, the present work also discusses the
      complexity involved in utilizing the methodology and possible errors arising
      during experimentation so as to implement this measurement tool more effectively
      in the future.

PMID- 22651241
TI  - Evaluation of body fat composition after linagliptin treatment in a rat model of
      diet-induced obesity: a magnetic resonance spectroscopy study in comparison with
      sibutramine.
AB  - The effects of linagliptin on fat content in diet-induced obese rats were
      compared with those of the appetite suppressant sibutramine. Female Wistar rats
      fed a high-fat diet (HFD) for 3 months received vehicle, linagliptin (10 mg/kg)
      or sibutramine (5 mg/kg) treatment orally, once daily for 6 additional weeks,
      while continuing the HFD. Magnetic resonance spectroscopy analysis of fat content
      was performed at baseline and at the end of the 6-week treatment period.
      Linagliptin treatment profoundly reduced hepatic fat compared with vehicle, with
      an effect comparable to that of sibutramine. The vehicle-corrected mean change
      (95% CI) from baseline in hepatic fat and intramyocellular lipid was -59.0% (
      104.3%, -13.6%; p = 0.015) and -62.1% (-131.6%, 7.4%; p = 0.073), respectively,
      for linagliptin compared with -54.3% (-101.5%, -7.1%; p = 0.027) and -72.4% (
      142.4%, -2.4%; p = 0.044), respectively, for sibutramine.

PMID- 22651238
TI  - Enhanced phosphorylation of Na(+)-Cl- co-transporter in experimental metabolic
      syndrome: role of insulin.
AB  - In the present study, we investigated the activity of the thiazide-sensitive NCC
      (Na(+)-Cl(-) co-transporter) in experimental metabolic syndrome and the role of
      insulin in NCC activation. Renal responses to the NCC inhibitor HCTZ
      (hydrochlorothiazide), as a measure of NCC activity in vivo, were studied in 12
      week-old ZO (Zucker obese) rats, a model of the metabolic syndrome, and in ZL
      (Zucker lean) control animals, together with renal NCC expression and molecular
      markers of NCC activity, such as localization and phosphorylation. Effects of
      insulin were studied further in mammalian cell lines with inducible and
      endogenous expression of this molecule. ZO rats displayed marked
      hyperinsulinaemia, but no differences in plasma aldosterone, compared with ZL
      rats. In ZO rats, natriuretic and diuretic responses to NCC inhibition with HCTZ
      were enhanced compared with ZL rats, and were associated with a decrease in BP
      (blood pressure). ZO rats displayed enhanced Thr(53) NCC phosphorylation and
      predominant membrane localization of both total and phosphorylated NCC, together
      with a different profile in expression of SPAK (Ste20-related proline/alanine
      rich kinase) isoforms, and lower expression of WNK4. In vitro, insulin induced
      NCC phosphorylation, which was blocked by a PI3K (phosphoinositide 3-kinase)
      inhibitor. Insulin-induced reduction in WNK4 expression was also observed, but
      delayed compared with the time course of NCC phosphorylation. In summary, we
      report increased NCC activity in hyperinsulinaemic rodents in conjunction with
      the SPAK expression profile consistent with NCC activation and reduced WNK4, as
      well as an ability of insulin to induce NCC stimulatory phosphorylation in vitro.
      Together, these findings indicate that hyperinsulinaemia is an important driving
      force of NCC activity in the metabolic syndrome with possible consequences for BP
      regulation.

PMID- 22651242
TI  - Consumer satisfaction among patients and their general practitioners about
      involving nurse specialists in primary care for patients with urinary
      incontinence.
AB  - BACKGROUND: Urinary incontinence (UI) is a very common problem, but existing
      guidelines on UI are not followed. To bring care in line with guidelines, we
      planned an intervention to involve nurse specialists on UI in primary care and
      assessed this in a randomised controlled trial. Alongside this intervention, we
      assessed consumer satisfaction among patients and general practitioners (GPs).
      METHODS: Patients' satisfaction with the care provided by either nurse
      specialists (intervention group) or GPs (control group), respectively, was
      measured with a self-completed questionnaire. GPs' views on the involvement of
      nurse specialists were measured in a structured telephone interview. RESULTS: The
      patient satisfaction score on the care offered by nurse specialists was 8.4
      (scale 1-10), vs. 6.7 for care-as-usual by GPs. Over 85% of patients would
      recommend nurse specialist care to their best friends and 77% of the GPs
      considered the role of the nurse specialist to be beneficial, giving it a mean
      score of 7.2. CONCLUSIONS: Although the sample was relatively small and the
      stability of the results only provisionally established, substituting UI care
      from GP to nurse specialist appears to be welcomed by both patients and GPs.
      Small changes like giving additional UI-specific information and devoting more
      attention to UI (which had been given little attention before) would provide a
      simple instrument to stimulate patients to change their behaviour in the right
      direction.

PMID- 22651243
TI  - Allenylphosphonates/allenylphosphine oxides as intermediates/precursors for
      intramolecular cyclization leading to phosphorus-based indenes, indenones,
      benzofurans, and isochromenes.
AB  - Utilizing internally available functional groups, a simple protocol for the
      efficient synthesis of phosphorus-based indenes, indenones, benzofurans, and
      isochromenes via intramolecular cyclization of allene intermediates/precursors is
      generated; the latter intermediates/precursors are conveniently obtained through
      aldehyde-, alkylidene-, and hydroxyl-functionalized propargyl alcohols and P(III)
      Cl precursors. The structures of key products have been unequivocally confirmed
      by X-ray crystallography.

PMID- 22651244
TI  - Nitrogen-rich compounds of the actinoids: dioxouranium(VI) 5,5'
      azobis[tetrazolide] pentahydrate and its unusually small uranyl angle.
AB  - Uranyl(VI) 5,5'-azobis[tetrazolide] pentahydrate was synthesized and
      characterized using X-ray crystallography, elemental analysis, UV/vis, MIR, FIR,
      and Raman spectroscopy. It is the second-most nitrogen rich compound of uranium
      (26.72 wt % N) and only the second structurally characterized uranium complex
      with a tetrazole ligand described in the literature. The compound's structure is
      characterized by an exceptionally small uranyl angle of 172.4(1) degrees , which
      provides information on the coordination properties of tetrazole ligands as they
      affect the donor's environment by strong steric and perhaps electrostatic
      repulsion. The compound showed luminescence under excitation with a near UV
      laser. The mean lifetime of its excited state was shorter than in the case of
      UO(2)(NO(3))(2).6H(2)O, indicating quenching by the ligand. Despite its high
      nitrogen content (and thus potentially explosive character), the title compound
      proved to be stable even under neutron radiation causing induced fission
      processes.

PMID- 22651245
TI  - Chloroplast-targeted bacterial RecA proteins confer tolerance to chloroplast DNA
      damage by methyl viologen or UV-C radiation in tobacco (Nicotiana tabacum)
      plants.
AB  - The nature and importance of the DNA repair system in the chloroplasts of higher
      plants under oxidative stress or UV radiation-induced genotoxicity was
      investigated via gain-of-functional approaches exploiting bacterial RecAs. For
      this purpose, transgenic tobacco (Nicotiana tabacum) plants and cell suspensions
      overexpressing Escherichia coli or Pseudomonas aeruginosa RecA fused to a
      chloroplast-targeting transit peptide were first produced. The transgenic tobacco
      plants maintained higher amounts of chloroplast DNA compared with wild-type (WT)
      upon treatments with methyl viologen (MV), a herbicide that generates reactive
      oxygen species (ROS) in chloroplasts. Consistent with these results, the
      transgenic tobacco leaves showed less bleaching than WT following MV exposure.
      Similarly, the MV-treated transgenic Arabidopsis plants overexpressing the
      chloroplast RecA homologue RECA1 showed weak bleaching, while the recA1 mutant
      showed opposite results upon MV treatment. In addition, when exposed to UV-C
      radiation, the dark-grown E. coli RecA-overexpressing transgenic tobacco cell
      suspensions, but not their WT counterparts, resumed growth and greening after the
      recovery period under light conditions. Measurements of UV radiation-induced
      chloroplast DNA damage using DraI assays (Harlow et al. 1994) with the
      chloroplast rbcL DNA probe and quantitative PCR analyses showed that the
      transgenic cell suspensions better repaired their UV-C radiation-induced
      chloroplast DNA lesions compared with WT. Taken all together, it was concluded
      that RecA-overexpressing transgenic plants are endowed with an increased
      chloroplast DNA maintenance capacity and enhanced repair activities, and
      consequently have a higher survival tolerance to genotoxic stresses. These
      observations are made possible by the functional compatibility of the bacterial
      RecAs in chloroplasts.

PMID- 22651246
TI  - Malignancy validation in a United States registry of rheumatoid arthritis
      patients.
AB  - BACKGROUND: Physician reporting is commonly used to ascertain adverse events or
      outcomes measured in epidemiologic studies. However, little is known on the
      accuracy of physician reported malignancies compared to pertinent medical record
      review in large cohort studies. METHODS: The Consortium of Rheumatology
      Researchers of North America (CORRONA) registry gathers physician-completed
      questionnaires for rheumatoid arthritis (RA) patients, including request for
      information on incident malignancies, approximately every three months. For
      incident malignancies reported from October 1st, 2001, through December 31st,
      2007, we retrospectively requested completion of a Targeted Adverse Event (TAE)
      form for additional information as well as primary source documents to adjudicate
      the malignancy reports. CORRONA has employed a prospective request for source
      documentation for these events since 2008. We classified each malignancy as
      definite, probable, possible, or not a malignancy. RESULTS: From 20,837 RA
      patients enrolled in CORRONA, 461 incident malignancies were initially reported
      on physician questionnaires. After review of returned source documents with
      adjudication, 234 were deemed definite, 69 probable, 101 possible, and 57 not an
      incident malignancy. The positive predictive value (PPV) of initial physician
      report of a malignancy versus "definite or probable" malignancy based on
      adjudication was 0.66 (95% CI 0.61 - 0.70). The PPV was 0.68 (95% CI 0.63 - 0.72)
      when the subsequent TAE form also confirmed the presence of malignancy. When
      possible malignancies were included, the PPV of physician-reported malignancies
      without a subsequent TAE form increased to 0.86 (0.83 - 0.89), and with a
      subsequent TAE form, 0.89 (0.85-0.91). CONCLUSION: Twelve percent of initial
      physician reports of incident malignancy could not be confirmed with review of
      source documents. The most common reason for lack of confirmation was inability
      to obtain documents or insufficient data in source materials. These results
      suggest that timely collection of relevant medical records and an adjudication
      process are required to improve the accuracy of cancer reporting in epidemiologic
      studies.

PMID- 22651248
TI  - Anatomical reconstruction of the patellar tendon using the fascia lata attached
      to the iliac bone following resection for soft tissue sarcoma: a case report.
AB  - A new reconstruction of the patellar tendon was performed in a 43-year-old
      patient who lost tendon and tibial tuberosity after a wide tumor resection for
      low-grade myofibroblastic sarcoma of the parapatellar tendon. In this technique,
      the patellar tendon was anatomically reconstructed using a fascia lata attached
      to the iliac bone. The iliac bone was fixed to the tibial bony trough with
      absorbable screws, and the fascia lata was fashioned into three branches: the
      central branch was folded through the tunnel in the patella, and the medial and
      lateral branches were tagged to the medial and lateral retinaculum, respectively,
      around the patella. The skin defect was covered by the bilateral head of the
      gastrocnemius flap and a split-thickness skin graft. At the 3-year follow-up, the
      active range of motion of the knee joint was 0 to 110 degrees. The functional
      result according to the Musculoskeletal Tumor Society scoring system was 97%.
      Radiographs showed that the grafted bone was united well to the tibial bone, and
      the grafted fascia was confirmed as a dark band on MRI. There was no evidence of
      disease and no complaint of the donor site. This procedure allows for the
      reconstruction of the patellar tendon in the original location. To our knowledge,
      this reconstructive procedure of the patellar tendon using the fascia lata
      attached to the iliac bone has never been reported in English literature.

PMID- 22651249
TI  - Factor X deficiency: an uncommon presentation of AL amyloidosis.
AB  - Factor X deficiency is the most common coagulation factor deficiency amongst
      patients with AL amyloidosis. It presumably occurs due to adsorption of factor X
      to amyloid fibrils. The deficiency of this factor, in conjunction with other
      hemostatic defects, can cause bleeding complications. A case of acquired factor X
      deficiency due to AL amyloidosis is reported, where abnormal coagulation
      parameters were the only presenting feature.

PMID- 22651250
TI  - Microorganisms causing pyogenic spondylitis: comparison of community and hospital
      acquired types.
AB  - Abstract   Pyogenic spondylitis is a common infectious disease caused by various
      microorganisms. It is difficult to predict the infecting microorganism at the
      time of initiation of treatment. Pneumonia is generally clarified into community
      or hospital-acquired types based on where the infection was acquired, and the
      infecting microorganisms are different for each type. We retrospectively analyzed
      20 cases of pyogenic spondylitis treated in our hospital and categorized the
      cases into community and hospital-acquired types. We also identified the
      infecting microorganisms and the rate of sepsis in each type. There were 12 cases
      of community-acquired and 8 of hospital-acquired infection. The major infecting
      microorganisms responsible for the community-acquired type were Gram-positive
      cocci, and those responsible for the hospital-acquired type were methicillin
      resistant Staphylococcus aureus and Gram-negative bacilli. The rate of sepsis was
      significantly different for both groups: 16% for the community-acquired type and
      75% for the hospital-acquired type. The classification of pyogenic spondylitis
      based on where the infection was acquired may be useful for predicting which
      microorganisms are responsible for the disease.

PMID- 22651247
TI  - Sex differences in human adipose tissues - the biology of pear shape.
AB  - Women have more body fat than men, but in contrast to the deleterious metabolic
      consequences of the central obesity typical of men, the pear-shaped body fat
      distribution of many women is associated with lower cardiometabolic risk. To
      understand the mechanisms regulating adiposity and adipose tissue distribution in
      men and women, significant research attention has focused on comparing adipocyte
      morphological and metabolic properties, as well as the capacity of preadipocytes
      derived from different depots for proliferation and differentiation. Available
      evidence points to possible intrinsic, cell autonomous differences in
      preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the
      microenvironment within each adipose tissue, and developmental factors. Gluteal
      femoral adipose tissues of women may simply provide a safe lipid reservoir for
      excess energy, or they may directly regulate systemic metabolism via release of
      metabolic products or adipokines. We provide a brief overview of the relationship
      of fat distribution to metabolic health in men and women, and then focus on
      mechanisms underlying sex differences in adipose tissue biology.

PMID- 22651251
TI  - Stabilization of organophosphorus hydrolase by entrapment in silk fibroin:
      formation of a robust enzymatic material suitable for surface coatings.
AB  - Organophosphates are some of the most acutely toxic compounds synthesized on an
      industrial scale, and organophosphorus hydrolase (OPH) has the ability to
      hydrolyze and inactivate a number of these chemicals. However, OPH activity is
      vulnerable to harsh environmental conditions that would accompany its practical
      utility in the field; a limitation that can also be extended to conditions
      required for incorporation of OPH into useful materials. Here we present evidence
      that entrapment of OPH in silk fibroin leads to stabilization of OPH activity
      under a variety of conditions that would otherwise reduce free enzyme activity,
      such as elevated temperature, UV light exposure and the presence of detergent.
      Silk fibroin entrapment of OPH also allowed for its dispersal into a polyurethane
      based coating that retained organophosphate hydrolysis activity after
      formulation, application and drying. Together, the data presented here
      demonstrate the utility of silk fibroin entrapment for the protection of OPH
      activity under a variety of environmental conditions.

PMID- 22651252
TI  - A highly diastereoselective decarboxylative mannich reaction of beta-keto acids
      with optically active N-sulfinyl alpha-imino esters.
AB  - A range of protected gamma-oxo-alpha-amino esters have been prepared in a highly
      regio- and stereoselective manner through the decarboxylative Mannich reaction of
      beta-keto acids with optically active N-tert-butanesulfinyl alpha-imino esters in
      the presence of 3 mol % La(OTf)(3) or 5 mol % Y(OTf)(3) at 20  degrees C.
      Preliminary mechanistic studies indicate that the reaction proceeds through imine
      addition followed by decarboxylation.

PMID- 22651253
TI  - HLA DNA typing: past, present, and future.
AB  - The human leukocyte antigen (HLA) class I and class II loci are the most
      polymorphic genes in the human genome, with a highly clustered and patchwork
      pattern of sequence motifs. In the three decades since the first HLA gene was
      isolated by molecular cloning (a cDNA clone of HLA-B7), thousands of alleles have
      been identified and the names and sequences of all known alleles have been
      curated in the IMGT/HLA database. This extensive allelic diversity made and
      continues to make high-resolution HLA DNA typing very challenging. The first
      attempt at HLA DNA typing involved restriction fragment length polymorphism
      (RFLP) analysis, but this approach had many limitations. The development of PCR
      in 1985 allowed for the amplification of the polymorphic exons of the HLA class I
      and class II genes and the analysis of the polymorphic sequence motifs with
      sequence-specific oligonucleotide (SSO) hybridization probes. The immobilization
      of these probes on membranes and later on beads, along with primer sets for
      sequence-specific priming (SSP), gave rise to the current set of HLA typing
      reagents. Sanger sequencing has provided high-resolution typing but, in many
      cases, genotyping 'ambiguity' remains an issue. In the past few years, the
      introduction of next-generation sequencing, with the critical properties of
      massively parallel and clonal sequencing, has significantly reduced HLA
      genotyping ambiguity. Here, our lab's efforts to develop high-resolution and high
      throughput HLA DNA typing using the 454 Sequencing System are reviewed, and the
      potential future developments and applications of HLA DNA typing are discussed.

PMID- 22651254
TI  - Nomenclature for factors of the HLA system, update February 2012.

PMID- 22651256
TI  - Regulation of small ubiquitin-like modifier-1, nuclear receptor coreceptor,
      histone deacetylase 3, and peroxisome proliferator-activated receptor-gamma in
      human adipose tissue.
AB  - BACKGROUND: This study investigated the regulation of peroxisome proliferator
      activated receptor-gamma (PPARgamma), the histone deacetylase 3 (HDAC3)-nuclear
      receptor coreceptor (NCoR) complex (a corepressor of transcription used by
      PPARgamma), and small ubiquitin-like modifier-1 (SUMO-1) (a posttranslational
      modifier of PPARgamma) in human adipose tissue and both adipocyte and macrophage
      cell lines. The objective was to determine whether there were alterations in the
      human adipose tissue gene expression levels of PPARgamma, HDAC3, NCoR, and SUMO-1
      associated either with obesity or with treatment of impaired glucose tolerance
      (IGT) subjects with insulin-sensitizing medications. METHODS: We obtained
      subcutaneous adipose tissue biopsies from 86 subjects with a wide range of body
      mass index (BMI) and insulin sensitivity (S(I)). Additionally, adipose tissue
      biopsies were obtained from a randomized subgroup of IGT subjects before and
      after 10 weeks of treatment with either pioglitazone or metformin. RESULTS: The
      adipose mRNA levels of PPARgamma, NCoR, HDAC3, and SUMO-1 correlated strongly
      with each other (P<0.0001); however, SUMO-1, NCoR, and HDAC3 gene expression were
      not significantly associated with BMI or S(I). Pioglitazone increased SUMO-1
      expression by 23% (P<0.002) in adipose tissue and an adipocyte cell line
      (P<0.05), but not in macrophages. Small interfering RNA (siRNA)-mediated
      knockdown of SUMO-1 decreased PPARgamma, HDAC3, and NCoR in THP-1 cells and
      increased tumor necrosis factor-alpha (TNF-alpha) induction in response to
      lipopolysaccharide (LPS). CONCLUSIONS: These results suggest that the coordinate
      regulation of SUMO-1, PPARgamma1/2, HDAC3, and NCoR may be more tightly
      controlled in macrophages than in adipocytes in human adipose and that these
      modulators of PPARgamma activity may be particularly important in the negative
      regulation of macrophage-mediated adipose inflammation by pioglitazone.

PMID- 22651370
TI  - Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella
      pneumoniae in mice.
AB  - BACKGROUND: Recent trials demonstrate increased pneumonia risk in chronic
      obstructive pulmonary disease patients treated with the inhaled corticosteroid
      (ICS) fluticasone propionate (FP). There is limited work describing FP effects on
      host defenses against bacterial pneumonia. METHODS: C57BL/6 mice received daily,
      nose-only exposure to nebulized FP or vehicle for 8 days, followed by pulmonary
      challenge with Klebsiella pneumoniae. Bacterial burden, phagocytosis, leukocyte
      recruitment, cytokine expression, nitric oxide release, and survival were
      measured. RESULTS: Inhaled FP increased bacterial burden in lungs and blood 48 h
      after infection but affected neither in vivo phagocytosis of bacteria by alveolar
      macrophages (AM) nor alveolar neutrophil recruitment. AM from FP-treated mice
      showed impaired expression of infection induced TNF-alpha, IP-10 (CXCL-10), and
      interleukin 6 (IL-6), and AM also showed a trend towards impaired intracellular
      pathogen control following in vivo infection. In vitro FP treatment resulted in a
      dose-dependent impairment of cytokine expression by AM. Furthermore, infection
      induced nitric oxide (but not hydrogen peroxide) production was impaired by FP in
      vivo and in vitro. FP decreased survival in this model. CONCLUSIONS: Exposure to
      inhaled FP impairs pulmonary clearance of K. pneumoniae in mice, an effect
      associated with greater systemic bacteremia and death. Decreased AM cytokine and
      nitric oxide expression parallel the failure to control infection. These results
      support the study of ICS effects on human pulmonary host defenses.

PMID- 22651371
TI  - Physical activity in patients with systemic lupus erythematosus and matched
      controls.
AB  - BACKGROUND: As physical activity reduces cardiovascular disease (CVD) in the
      general population, studies concerning the frequency of physical activity in
      patients with systemic lupus erythematosus (SLE) are needed. Earlier studies
      indicate that patients with SLE are physically inactive but there are few studies
      that compare physical activity in SLE to that in the general population. The aim
      of this study was to examine different aspects of physical activity in patients
      with SLE and population controls and to investigate how they relate to disease
      activity and organ damage. METHODS: Two hundred and seventy-two patients with SLE
      and 272 population controls, individually matched for age, gender, and living
      region, were investigated clinically. For patients, the investigation included
      assessment of disease activity using the SLE Disease Activity Index (SLEDAI) and
      organ damage using the Systemic Lupus International Collaborating
      Clinics/American College of Rheumatology (SLICC) Damage Index. All participants
      filled out an extensive questionnaire concerning physical activity, exercise
      capacity, and sedentary behaviour. RESULTS: The mean age of the patients was 47
      (SD 15) years. Patients reported lower (p < 0.001) capacity for walking, jogging,
      and running and more limiting factors for these activities than controls (p <
      0.001). Patients exercised less often than controls (p < 0.01) and patients with
      SLICC >= 2 points reported less physical activity on 'low to moderate' intensity
      compared to their controls (p < 0.05). Sedentary behaviour was reported by 18% of
      the patients and 26% of the controls (ns). CONCLUSION: Patients with SLE reported
      lower exercise capacity and less frequent exercise than controls. Additionally,
      patients with more organ damage reported less physical activity, and these,
      together with patients who have a sedentary behaviour, should be the focus of
      intervention programmes to support increased physical activity and exercise in
      SLE.

PMID- 22651372
TI  - The ultrastructure of Placus striatus and a revision of the family Placidae
      (Ciliophora).
AB  - The first ultrastructural description of the genus Placus is presented. Each
      somatic kinetosome has a cone-shaped axosomal plate, nonoverlapping postciliary
      microtubules, an anteriorly directed kinetodesmal fiber, and a radial ribbon of
      transverse microtubules, which extend laterally under the ciliary furrow and
      insert in the cortical ridge. A closed ring of paired kinetosomes encircles the
      cytostome. A brosse begins adjacent to the oral pairs and extends posteriorly for
      one-fourth to one-half the cell's length. Autapomorphies for Placus include
      bowling pin-shaped toxicysts extruded onto a distinct area of the cell surface
      immediately posterior to the brosse, and a brosse kinety consisting of a single
      row of paired cilia. Placus and its sister taxon Spathidiopsis both have
      spiraling kineties composed of single cilia inserted into the side of the ciliary
      furrow. Spathidiopsis can be distinguished from Placus because it has a brosse
      consisting of two kineties (i.e. one composed of paired cilia, the other of
      single cilia), a row of rod-shaped toxicyst-bearing palps extending around one
      side of the oral area and along the length of the brosse, and a mid-cell cortical
      inpocketing containing toxicysts and a segment of the brosse. A revised listing
      of species assigned to the family Placidae is given.

PMID- 22651257
TI  - Knowledge translation of research findings.
AB  - BACKGROUND: One of the most consistent findings from clinical and health services
      research is the failure to translate research into practice and policy. As a
      result of these evidence-practice and policy gaps, patients fail to benefit
      optimally from advances in healthcare and are exposed to unnecessary risks of
      iatrogenic harms, and healthcare systems are exposed to unnecessary expenditure
      resulting in significant opportunity costs. Over the last decade, there has been
      increasing international policy and research attention on how to reduce the
      evidence-practice and policy gap. In this paper, we summarise the current
      concepts and evidence to guide knowledge translation activities, defined as T2
      research (the translation of new clinical knowledge into improved health). We
      structure the article around five key questions: what should be transferred; to
      whom should research knowledge be transferred; by whom should research knowledge
      be transferred; how should research knowledge be transferred; and, with what
      effect should research knowledge be transferred? DISCUSSION: We suggest that the
      basic unit of knowledge translation should usually be up-to-date systematic
      reviews or other syntheses of research findings. Knowledge translators need to
      identify the key messages for different target audiences and to fashion these in
      language and knowledge translation products that are easily assimilated by
      different audiences. The relative importance of knowledge translation to
      different target audiences will vary by the type of research and appropriate
      endpoints of knowledge translation may vary across different stakeholder groups.
      There are a large number of planned knowledge translation models, derived from
      different disciplinary, contextual (i.e., setting), and target audience
      viewpoints. Most of these suggest that planned knowledge translation for
      healthcare professionals and consumers is more likely to be successful if the
      choice of knowledge translation strategy is informed by an assessment of the
      likely barriers and facilitators. Although our evidence on the likely
      effectiveness of different strategies to overcome specific barriers remains
      incomplete, there is a range of informative systematic reviews of interventions
      aimed at healthcare professionals and consumers (i.e., patients, family members,
      and informal carers) and of factors important to research use by policy makers.
      SUMMARY: There is a substantial (if incomplete) evidence base to guide choice of
      knowledge translation activities targeting healthcare professionals and
      consumers. The evidence base on the effects of different knowledge translation
      approaches targeting healthcare policy makers and senior managers is much weaker
      but there are a profusion of innovative approaches that warrant further
      evaluation.

PMID- 22651373
TI  - Dapagliflozin has no effect on markers of bone formation and resorption or bone
      mineral density in patients with inadequately controlled type 2 diabetes mellitus
      on metformin.
AB  - AIMS: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2)
      inhibitor, reduces hyperglycaemia in patients with type 2 diabetes (T2DM) by
      increasing urinary glucose excretion. Owing to its mechanism of action,
      dapagliflozin could potentially affect the renal tubular transportation of bone
      minerals. Therefore, markers of bone formation and resorption and bone mineral
      density (BMD) were evaluated in patients with T2DM after 50 weeks of
      dapagliflozin treatment. METHODS: This international, multi-centre, randomized,
      parallel-group, double-blind, placebo-controlled study (ClinicalTrials.gov
      NCT00855166) enrolled patients with T2DM (women 55-75 years and men 30-75 years;
      HbA1c 6.5-8.5%; BMI >= 25 kg/m(2) ; body weight <= 120 kg) whose T2DM was
      inadequately controlled on metformin. One hundred and eighty-two patients were
      randomly assigned 1:1 to receive dapagliflozin 10 mg/day or placebo added to open
      label metformin for a 24-week double-blind treatment period followed by a 78-week
      site- and patient-blinded extension period. At week 50, serum markers of bone
      formation (procollagen type 1 N-terminal propeptide; P1NP) and resorption (C
      terminal cross-linking telopeptides of type I collagen; CTX), bone mineral
      density (BMD) as assessed by standardized Dual-Energy X-ray Absorptiometry (DXA)
      measurements and adverse events of fracture were evaluated as safety objectives.
      RESULTS: One hundred and sixty-five patients (90.7%) completed the first 50
      weeks. Compared with placebo, no significant changes from baseline in P1NP, CTX
      or BMD were identified over 50 weeks of dapagliflozin treatment, with no
      significant treatment-by-gender interactions. No fractures were reported.
      CONCLUSIONS: Dapagliflozin had no effect on markers of bone formation and
      resorption or BMD after 50 weeks of treatment in both male and post-menopausal
      female patients whose T2DM was inadequately controlled on metformin.

PMID- 22651374
TI  - Smoking cessation is followed by a sharp but transient rise in the incidence of
      overt autoimmune hypothyroidism - a population-based, case-control study.
AB  - BACKGROUND: Current smoking is associated with a low prevalence of thyroid
      autoantibodies. On the other hand, smoking withdrawal enhances thyroid
      autoantibody level and may be a risk factor for the development of
      hypothyroidism. The aim of this study was to assess the association between
      smoking habits (smoking cessation in particular) and development of autoimmune
      hypothyroidism. DESIGN: Population-based, case-control study. PARTICIPANTS: Cases
      (n = 140) newly diagnosed with primary autoimmune overt hypothyroidism were
      identified prospectively by population monitoring (2,027,208 person-years of
      observation) of all thyroid function tests performed in the two well-defined
      geographical areas. Individually, age-, sex- and region-matched euthyroid
      controls (n = 560) were simultaneously included from the same population.
      MEASUREMENTS: Participants gave details on smoking habits including smoking
      withdrawal and other lifestyle factors. Smoking habits were verified by measuring
      urinary cotinine (a nicotine metabolite). RESULTS: Incident hypothyroidism was
      very common in people who had recently stopped smoking: OR vs never smokers (95%
      CI); quit smoking <1 years, 7.36 (2.27-23.9); 1-2 years, 6.34 (2.59-15.3); 3-10
      years, 0.75 (0.30-1.87); >10 years, 0.76 (0.38-1.51). Results were consistent in
      both sexes and irrespective of age. Within two years after smoking cessation, the
      percentage of hypothyroid cases attributable to cessation of smoking was 85%. The
      current smoking was not associated with altered risk of developing overt
      hypothyroidism [OR, 0.92 (0.57-1.48)]. CONCLUSIONS: The risk of having overt
      autoimmune hypothyroidism diagnosed is more than 6-fold increased the first 2
      years after cessation of smoking. Clearly, smoking cessation is vital to prevent
      death and severe disease. However, awareness of hypothyroidism should be high in
      people who have recently quit smoking, and virtually any complaint should lead to
      thyroid function testing.

PMID- 22651375
TI  - A unified approach to trans-hydrindane sesterterpenoids.
AB  - A synthetic approach to several sesterterpenoids containing an isopropyl trans
      hydrindane system is presented. Its most remarkable feature is the stereochemical
      diversification of a common precursor through the choice of different
      hydrogenation conditions.

PMID- 22651376
TI  - A visual analytics approach for models of heterogeneous cell populations.
AB  - In recent years, cell population models have become increasingly common. In
      contrast to classic single cell models, population models allow for the study of
      cell-to-cell variability, a crucial phenomenon in most populations of primary
      cells, cancer cells, and stem cells. Unfortunately, tools for in-depth analysis
      of population models are still missing. This problem originates from the
      complexity of population models. Particularly important are methods to determine
      the source of heterogeneity (e.g., genetics or epigenetic differences) and to
      select potential (bio-)markers. We propose an analysis based on visual analytics
      to tackle this problem. Our approach combines parallel-coordinates plots, used
      for a visual assessment of the high-dimensional dependencies, and nonlinear
      support vector machines, for the quantification of effects. The method can be
      employed to study qualitative and quantitative differences among cells. To
      illustrate the different components, we perform a case study using the
      proapoptotic signal transduction pathway involved in cellular apoptosis.

PMID- 22651377
TI  - Cell-derived matrix coatings for polymeric scaffolds.
AB  - Cells in culture deposit a complex extracellular matrix that remains intact
      following decellularization and possesses the capacity to modulate cell
      phenotype. The direct application of such decellularized matrices (DMs) to 3D
      substrates is problematic, as transport issues influence the homogeneous
      deposition, decellularization, and modification of DM surface coatings. In an
      attempt to address this shortcoming, we hypothesized that DMs deposited by human
      mesenchymal stem cells (MSCs) could be transferred to the surface of polymeric
      scaffolds while maintaining their capacity to direct cell fate. The ability of
      the transferred DM (tDM)-coated scaffolds to enhance the osteogenic
      differentiation of undifferentiated and osteogenically induced MSCs under
      osteogenic conditions in vitro was confirmed. tDM-coated scaffolds increased MSC
      expression of osteogenic marker genes (BGLAP, IBSP) and intracellular alkaline
      phosphatase production. In addition, undifferentiated MSCs deposited
      significantly more calcium when seeded onto tDM-coated scaffolds compared with
      control scaffolds. MSC-seeded tDM-coated scaffolds subcutaneously implanted in
      nude rats displayed significantly higher blood vessel density after 2 weeks
      compared with cells on uncoated scaffolds, but we did not observe significant
      differences in mineral deposition after 8 weeks. These data demonstrate that DM
      coatings produced in 2D culture can be successfully transferred to 3D substrates
      and retain their capacity to modulate cell phenotype.

PMID- 22651378
TI  - Human telomere sequence DNA in water-free and high-viscosity solvents: G
      quadruplex folding governed by Kramers rate theory.
AB  - Structures formed by human telomere sequence (HTS) DNA are of interest due to the
      implication of telomeres in the aging process and cancer. We present studies of
      HTS DNA folding in an anhydrous, high viscosity deep eutectic solvent (DES)
      comprised of choline choride and urea. In this solvent, the HTS DNA forms a G
      quadruplex with the parallel-stranded ("propeller") fold, consistent with
      observations that reduced water activity favors the parallel fold, whereas
      alternative folds are favored at high water activity. Surprisingly, adoption of
      the parallel structure by HTS DNA in the DES, after thermal denaturation and
      quick cooling to room temperature, requires several months, as opposed to less
      than 2 min in an aqueous solution. This extended folding time in the DES is, in
      part, due to HTS DNA becoming kinetically trapped in a folded state that is
      apparently not accessed in lower viscosity solvents. A comparison of times
      required for the G-quadruplex to convert from its aqueous-preferred folded state
      to its parallel fold also reveals a dependence on solvent viscosity that is
      consistent with Kramers rate theory, which predicts that diffusion-controlled
      transitions will slow proportionally with solvent friction. These results provide
      an enhanced view of a G-quadruplex folding funnel and highlight the necessity to
      consider solvent viscosity in studies of G-quadruplex formation in vitro and in
      vivo. Additionally, the solvents and analyses presented here should prove
      valuable for understanding the folding of many other nucleic acids and
      potentially have applications in DNA-based nanotechnology where time-dependent
      structures are desired.

PMID- 22651379
TI  - Monopicolinate cyclen and cyclam derivatives for stable copper(II) complexation.
AB  - The syntheses of a new 1,4,7,10-tetraazacyclododecane (cyclen) derivative bearing
      a picolinate pendant arm (HL1), and its 1,4,8,11-tetraazacyclotetradecane
      (cyclam) analogue HL2, were achieved by using two different selective-protection
      methods involving the preparation of cyclen-bisaminal or phosphoryl cyclam
      derivatives. The acid-base properties of both compounds were investigated as well
      as their coordination chemistry, especially with Cu(2+), in aqueous solution and
      in solid state. The copper(II) complexes were synthesized, and the single crystal
      X-ray diffraction structures of compounds of formula [Cu(HL)](ClO(4))(2).H(2)O (L
      = L1 or L2), [CuL1](ClO(4)) and [CuL2]Cl.2H(2)O, were determined. These studies
      revealed that protonation of the complexes occurs on the carboxylate group of the
      picolinate moiety. Stability constants of the complexes were determined at 25.0 
      degrees C and ionic strength 0.10 M in KNO(3) using potentiometric titrations.
      Both ligands form complexes with Cu(2+) that are thermodynamically very stable.
      Additionally, both HL1 and HL2 exhibit an important selectivity for Cu(2+) over
      Zn(2+). The kinetic inertness in acidic medium of both complexes of Cu(2+) was
      evaluated by spectrophotometry revealing that [CuL2](+) is much more inert than
      [CuL1](+). The determined half-life values also demonstrate the very high kinetic
      inertness of [CuL2](+) when compared to a list of copper(II) complexes of other
      macrocyclic ligands. The coordination geometry of the copper center in the
      complexes was established in aqueous solution from UV-visible and electron
      paramagnetic resonance (EPR) spectroscopy, showing that the solution structures
      of both complexes are in excellent agreement with those of crystallographic data.
      Cyclic voltammetry experiments point to a good stability of the complexes with
      respect to metal ion dissociation upon reduction of the metal ion to Cu(+) at
      about neutral pH. Our results revealed that the cyclam-based ligand HL2 is a very
      attractive receptor for copper(II), presenting a fast complexation process, a
      high kinetic inertness, and important thermodynamic and electrochemical
      stability.

PMID- 22651382
TI  - Borrelia burgdorferi visualized in Ixodes scapularis tick excrement by
      immunofluorescence.
AB  - The enzootic cycle of Borrelia burgdorferi, the etiologic agent of Lyme disease,
      involves Ixodes spp. ticks and vertebrates. Resident tick Borrelia, harbored
      inside the midgut, are eventually expelled with the tick's saliva into the
      vertebrate host when a tick consumes a blood meal. During this 4- to 5-day
      feeding period I. scapularis will defecate onto the host's skin. Previously we
      detected borrelial DNA in tick feces throughout engorgement. In this study we
      report the microscopic examination for B. burgdorferi in nymphal excrement. Using
      immunofluorescence assays, we observed Borrelia in all mouse skin and capsule
      fecal swabs tested, although we could not culture the spirochetes. These results
      update our previous analysis by revealing that spirochetes can also be visualized
      in tick excrement. Furthermore, the results emphasize that borrelial
      contamination by defecation is a possibility, and that caution should be
      exercised by researchers investigating pathogen/host/vector interactions. The
      biological significance of the presence of non-culturable Borrelia in tick feces
      during engorgement is unclear.

PMID- 22651380
TI  - Interactions of commonly used dietary supplements with cardiovascular drugs: a
      systematic review.
AB  - BACKGROUND: The objective of this systematic review was to examine the benefits,
      harms and pharmacokinetic interactions arising from the co-administration of
      commonly used dietary supplements with cardiovascular drugs. Many patients on
      cardiovascular drugs take dietary supplements for presumed benefits and may be at
      risk for adverse supplement-drug interactions. METHODS: The Allied and
      Complementary Medicine Database, the Cochrane Library, EMBASE, International
      Bibliographic Information on Dietary Supplements and MEDLINE were searched from
      the inception of the review to October 2011. Grey literature was also
      reviewed.Two reviewers independently screened records to identify studies
      comparing a supplement plus cardiovascular drug(s) with the drug(s) alone.
      Reviewers extracted data using standardized forms, assessed the study risk of
      bias, graded the strength of evidence and reported applicability. RESULTS:
      Evidence was obtained from 65 randomized clinical trials, 2 controlled clinical
      trials and 1 observational study. With only a few small studies available per
      supplement, evidence was insufficient for all predefined gradable clinical
      efficacy and harms outcomes, such as mortality and serious adverse events. One
      long-term pragmatic trial showed no benefit from co-administering vitamin E with
      aspirin on a composite cardiovascular outcome. Evidence for most intermediate
      outcomes was insufficient or of low strength, suggesting no effect. Incremental
      benefits were noted for triglyceridemia with omega-3 fatty acid added to statins;
      and there was an improvement in levels of high-density lipoprotein cholesterol
      with garlic supplementation when people also consumed nitrates CONCLUSIONS:
      Evidence of low-strength indicates benefits of omega-3 fatty acids (plus statin,
      or calcium channel blockers and antiplatelets) and garlic (plus nitrates or
      warfarin) on triglycerides and HDL-C, respectively. Safety concerns, however,
      persist.

PMID- 22651381
TI  - First report of Toxoplasma gondii prevalence in Tibetan pigs in Tibet, China.
AB  - Toxoplasma gondii infection is widely prevalent in humans and animals, including
      pigs throughout the world. In this study, the seroprevalence of T. gondii
      infection in Tibetan pigs in China was investigated for the first time. A total
      of 427 serum samples were collected from Tibetan pigs in Nyingchi prefecture,
      Tibet, between April and December 2010, and were assayed for antibodies to T.
      gondii using the modified agglutination test (MAT). Ninety-seven (22.72%) pigs
      were found to be positive with MAT titers of 1:25 or higher. Slaughter pigs had
      the highest seroprevalence, compared with seroprevalence in fattening pigs,
      growing pigs, or piglets, although the difference was not statistically
      significant (p>=0.05). The results of the present survey indicate that T. gondii
      is highly prevalent in Tibetan pigs in Tibet, which poses a significant public
      health concern in this unique region of the world.

PMID- 22651384
TI  - Willingness to pay for mosquito control: how important is West Nile virus risk
      compared to the nuisance of mosquitoes?
AB  - Public health programs that control mosquitoes and other disease vectors have the
      added benefit of reducing residents' exposure to pest insects. We surveyed
      homeowners in Madison, Wisconsin, and used an economic valuation method, stated
      choice experiments, to measure willingness to pay (WTP) for control of West Nile
      virus (WNV)-transmitting and nuisance mosquitoes under current and increased
      levels of WNV risk. Under current WNV risk levels (approximately 1 in 250,000),
      the average Madison survey respondent was not willing to pay for programs that
      targeted West Nile-transmitting mosquitoes only (WTP=-$21, 95% [CI -$63, $20]),
      while WTP for a reduction in nuisance mosquitoes was substantial (WTP=$147, 95%
      [CI $109, $186]). As the risk of WNV was increased, WTP for control of disease
      carrying mosquitoes also increased (WTP=$158; 95% CI [$111, $206] at the highest
      risk level), but WTP for nuisance control remained high (WTP=$108; 95% CI [$78,
      $138]). Among homeowners in our sample, the "nuisance factor" was more important
      than the "disease factor" in terms of respondents' demand for mosquito control.

PMID- 22651383
TI  - Effect of ambient temperature on the clinical manifestations of experimental
      diffuse cutaneous leishmaniasis in a rodent model.
AB  - Dermal species of Leishmania have a relatively broad temperature range for
      optimal growth in vitro, with temperature differences accompanied by a form
      change. This suggests that when the host is living in moderate temperatures (22
      degrees C), infection may proceed at temperatures lower than those that occur in
      tropical regions (32 degrees C), and a different clinical expression of the
      disease due to a different parasitic form may result. The aim of this study was
      to investigate the effect of environmental temperature on the clinical expression
      of the disease. BALB/C mice infected with Leishmania mexicana were housed at 32
      degrees +/-2 degrees C or 22 degrees +/-1 degrees C, and assessed for the
      development of inflammation and the presence of parasites in organs using PCR and
      immunohistology. The clinical expression of leishmaniasis at 32 degrees C
      included inflammation at the site of inoculation with swelling of the nose and
      tail, whereas at 22 degrees C, up to 50% of the infected mice developed dry
      exfoliative dermatitis with alopecia on the dorsum. In both cases, parasite
      colonization was confirmed in the skin, with parasites at more external locations
      at 22 degrees C. Parasite visceralization was confirmed in all internal organs
      and glands in both cases based on PCR and immunohistology. In conclusion, the
      clinical expression of diffuse leishmaniasis by Leishmania mexicana in laboratory
      mice is modified by temperature, from nodular inflammation at 32 degrees C, to
      dry exfoliative dermatitis and alopecia at 22 degrees C, with parasite
      visceralization in both cases.

PMID- 22651386
TI  - Prevalence of Coxiella burnetii in Hungary: screening of dairy cows, sheep,
      commercial milk samples, and ticks.
AB  - Q fever is an important zoonotic disease caused by Coxiella burnetii. There are
      few reliable data about C. burnetii infection available. The aim of this study
      was to assess the importance and potential infectious sources of Q fever in
      Hungary. A total of 215 milk samples (10 individual samples from each herd and 1
      bulk tank milk sample from each cattle herd), and 400 serum samples (20 from each
      herd) were tested from 15 dairy cattle herds and 5 sheep flocks located in
      different parts of Hungary. The study found 19.3% (58/300) and 38.0% (57/150)
      seropositivity in cattle, and 0% (0/100) and 6.0% (3/50) seropositivity in sheep,
      by complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA),
      respectively. C. burnetii DNA was detected by IS1111 element-based TaqMan real
      time polymerase chain reaction (PCR) in 8.7% (13/150) of individual dairy cow
      milk samples, 4.0% (2/50) of individual sheep milk samples, and 66.7% (10/15) of
      dairy bulk tank milk samples. Samples taken from nine different commercially
      available pasteurized cow milk products from different Hungarian producers were
      also tested for the presence of C. burnetii DNA, and eight of these samples were
      found to be positive (88.9%). The real-time PCR examination of 5402 ixodid ticks
      collected from different parts of the country yielded negative results. Knowledge
      of the true prevalence of Q fever is crucial for policymakers involved in
      evidence-based decision making.

PMID- 22651387
TI  - Epizootiology of trichinellosis in pigs and wild boars in Western Romania, 1998
      2011.
AB  - This article reports for the first time data regarding trichinellosis in
      sacrificed animals (domestic pigs and wild boars) inspected during the period
      from January 1998 to November 2011 in the largest of the Romanian counties. The
      data were collected from the Veterinary Public Health Department of Timis County.
      A total of 5,586,431 domestic pigs on farms, 609,325 pigs in private households,
      and 823 wild boars were examined during the study period. The results indicated
      that 681 domestic pigs (0.01%) on farms and 407 pigs in private households
      (0.07%) were found to be infected with Trichinella. Regarding wild boars,
      infection was detected in only 4 animals (0.5%). Although no infected animals
      have recently been identified during routine examinations (2009-2011), human
      outbreaks continue to occur yearly, and the main factors for these include
      improper handling by the population.

PMID- 22651388
TI  - Seroprevalence of major bovine-associated zoonotic infectious diseases in the Lao
      People's Democratic Republic.
AB  - Bovine-associated zoonotic infectious diseases pose a significant threat to human
      health in the Lao People's Democratic Republic (Lao PDR). In all, 905 cattle and
      buffalo serum samples collected in northern Lao PDR in 2006 were used to
      determine seroprevalence of five major bovine zoonotic infectious diseases that
      included Taenia saginata cysticercosis, bovine tuberculosis, Q-fever, bovine
      brucellosis, and bovine leptospirosis. Five enzyme-linked immunosorbent assays
      (ELISAs) were used to test for the presence of antibodies to the diseases, except
      Taenia saginata, for which we tested for the presence of Taenia metacestode
      circulating antigens. The overall highest prevalence was for T. saginata (46.4%),
      with lower prevalence for Q-fever (4%), leptospirosis (3%), tuberculosis (1%),
      and brucellosis (0.2%). Although there were no significant differences in the
      proportion of seroprevalence between sex and age of the animals sampled, there
      were significant differences between the provincial distributions. Further
      studies are required to determine the seroprevalence of these infections in other
      locations in Lao PDR, as well as other animal species including humans, in order
      to develop effective prevention and control strategies. This is the first study
      to investigate the prevalence of bovine zoonotic infectious agents in the Lao
      PDR. Positivity was demonstrated for all diseases investigated, with the highest
      prevalence for T. saginata antigen and Coxiella burnetti antibodies. For T.
      saginata, there were significant differences in the provincial distribution.
      Approximately 16% seroprevalence of Coxiella burnetti was noted in Xayabuly
      Province; however, there are no clear reasons why this was the case, and further
      studies are required to determine risk factors associated with this observation.

PMID- 22651389
TI  - Reverse transcription PCR-based detection of Crimean-Congo hemorrhagic fever
      virus isolated from ticks of domestic ruminants in Kurdistan province of Iran.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal viral vector-borne
      zoonosis which has a mortality rate of up to 30% without treatment in humans.
      CCHF virus is transmitted to humans by ticks, predominantly from the Hyalomma
      genus. Following the report of two confirmed and one suspected death due to CCHF
      virus in Kurdistan province of Iran in 2007, this study was undertaken to
      determine the fauna of hard ticks on domestic ruminants (cattle, sheep, and
      goats) and their possible infection with CCHF virus using reverse transcription
      PCR technique. This is the first detection of CCHF virus in ticks from the
      Kurdistan province of Iran. Overall, 414 ixodid ticks were collected from two
      districts in this province. They represented four genera from which 10 separate
      species were identified. The Hyalomma genus was the most abundant tick genus
      (70%). It was the only genus shown to be infected with the CCHF virus using RT
      PCR technique. The number of ticks positive for CCHF virus was 5 out of 90 (5.6%)
      adult ticks. The three remaining genera (Haemaphysalis, Rhipicephalus, and
      Dermacentor) were all negative following molecular survey. Four of the five
      virally-infected ticks were from cattle mainly in the Sanandaj district. We
      concluded that CCHF virus is present in the Hyalomma ticks on domestic ruminants
      (cattle) in Kurdistan province of Iran.

PMID- 22651390
TI  - Molecular detection of Leishmania major kDNA from wild rodents in a new focus of
      zoonotic cutaneous leishmaniasis in an Oriental region of Iran.
AB  - Human cutaneous leishmaniasis is one of the most challenging public health issues
      in many tropical and subtropical countries of the world, including Iran. More
      than half (54%) of the new zoonotic cutaneous leishmaniasis (ZCL) cases among the
      Eastern Mediterranean countries were reported from Iran in 2008. The detection of
      Leishmania parasites in rodents is essential to incriminate them as probable
      reservoir hosts of ZCL infection. As a result of the annual detection of about
      200-250 clinical ZCL cases in the Jask district of southern Iran, feral rodents
      were trapped, identified to species level, and examined for Leishmania presence
      by preparing routine blood smears on microscopic slides from 2007 to 2008.
      Overall, 27 Tatera indica, 17 Gerbillus nanus, 29 Meriones persicus, 26 M.
      hurrianae, and 7 M. libycus were identified. Females of T. indica, M. hurrianae,
      and G. nanus appeared to be naturally infected with the protozoan parasite, L.
      major. This is the first report of microscopic and molecular detection of this
      trypanosomatid parasite infecting these three rodents reported from Hormozgan
      province in southeast Iran. More than three-quarters (82%) of the parasite
      infected rodents came from the eastern plain of this province, but none of the
      other rodents were found to be smear-positive or kinetoplast DNA-positive by PCR.
      M. hurrianae, G. nanus, and T. indica are therefore incriminated as three
      potential reservoir hosts of L. major in Oriental parts of Iran.

PMID- 22651385
TI  - Molecular evidence indicates that Phlebotomus major sensu lato (Diptera:
      Psychodidae) is the vector species of the recently-identified sandfly fever
      Sicilian virus variant: sandfly fever turkey virus.
AB  - Sandfly fever turkey virus (SFTV) is a recently-discovered sandfly fever Sicilian
      virus (SFSV) variant (family Bunyaviridae, genus Phlebovirus), characterized
      during retrospective evaluation of febrile disease outbreaks in Turkey. In
      addition to causing sandfly fever, SFTV was observed to induce elevation of liver
      enzymes, and to cause thrombocytopenia in affected individuals. This study was
      conducted to identify vectors for phleboviruses including SFTV in Ankara
      province, Turkey, where evidence indicates ongoing circulation of SFTV, as well
      as Toscana virus. Sandfly sampling was performed in Ankara province in the
      vicinity or in animal housing facilities in 15 peri-domestic sites. Male
      sandflies were identified morphologically, whereas females were evaluated
      individually for Phlebovirus RNA via a nested-PCR assay with consensus primers.
      Selected individuals and PCR-positive sandflies were subjected to barcoding via
      cytochrome c oxidase sequence analyses. The source of blood meals in virus
      infected sandflies was investigated using a multiplexed PCR targeting the
      mitochondrial cytochrome b gene of various vertebrates. A total of 667 sandflies
      were captured in 11 locations. Morphological identification of males (n=226)
      revealed Phlebotomus major sensu lato as the most abundant species (38.9%),
      followed by Phlebotomus sergenti (20.4%), Phlebotomus halepensis (17.7%),
      Phlebotomus papatasi (10.2%), Phlebotomus simici (3.98%), Larrousius spp.
      (3.53%), Phlebotomus tobbi (1.32%), Phlebotomus perfiliewi perfiliewi (1.32%),
      and others. Virus sequences were detected in 3 (3/441) sandflies, two of which
      were characterized as P. major s.l. via barcoding. The detected sequences in
      sandflies were identified as SFTV, and were identical or similar to sequences
      from patients from the same area and the prototype SFTV strain. Bovine and human
      blood meals were demonstrated in SFTV-infected sandflies. P. major s.l. has been
      identified as the vector species for SFTV. Bovidae need to be evaluated as
      probable amplifying hosts for SFTV.

PMID- 22651391
TI  - Implications of spatial patterns of roosting and movements of American robins for
      West Nile virus transmission.
AB  - The arrival of West Nile virus (WNV) in North America has led to interest in the
      interaction between birds, the amplification hosts of WNV, and Culex mosquitoes,
      the primary WNV vectors. American robins (Turdus migratorius) are particularly
      important amplification hosts of WNV, and because the vector Culex mosquitoes are
      primarily nocturnal and feed on roosting birds, robin communal roosting behavior
      may play an important role in the transmission ecology of WNV. Using data from 43
      radio-tracked individuals, we determined spatial and temporal patterns of robin
      roosting behavior, and how these patterns related to the distribution of WNV
      infected mosquitoes. Use of the communal roost and fidelity to foraging areas was
      highly variable both within and among individual robins, and differed markedly
      from patterns documented in a previous study of robin roosting. Although there
      were clear seasonal patterns to both robin roosting and WNV occurrence, there was
      no significant relationship between communal roosting by robins and temporal or
      spatial patterns of WNV-positive mosquitoes. Our results suggest that, although
      robins may be important as WNV hosts, communal roosts are not necessarily
      important for WNV amplification. Other factors, including the availability and
      distribution of high-quality mosquito habitat and favorable weather for mosquito
      reproduction, may influence the importance of robin roosts for local WNV
      amplification and transmission.

PMID- 22651392
TI  - Babesia microti in adult Dermacentor reticulatus ticks from eastern Poland.
AB  - A total of 468 adult Dermacentor reticulatus ticks (298 females and 170 males)
      collected by flagging in the forests of Lubelskie province, eastern Poland, were
      analyzed by PCR and nested-PCR for the presence of Babesia microti DNA. In all,
      21 ticks (4.5%) were found to be infected with B. microti. The infection rate in
      females (5.0%) was slightly greater than in males (3.5%). Detection of B. microti
      for the first time in adult D. reticulatus ticks suggests that this species
      should be considered as a potential vector of B. microti in Europe.

PMID- 22651393
TI  - Isolation and characterization of a new strain of lymphocytic choriomeningitis
      virus from rodents in southwestern France.
AB  - A total of 821 tissue samples from rodents trapped during field campaigns
      organized in Europe and Africa were screened for the presence of arenaviruses by
      molecular methods and cell culture inoculation when feasible. Two Mus musculus
      domesticus trapped in the southwestern part of France were infected with a
      potentially new strain of lymphocytic choriomeningitis virus (LCMV), here
      referred to as LCMV strain HP65-2009, which was isolated and genetically
      characterized by whole genome sequencing. Genetic and phylogenetic analyses
      comparing LCMV HP65-2009 with 26 other LCMV strains showed that it represents a
      novel highly-divergent strain within the group of Mus musculus-associated LCMV.

PMID- 22651394
TI  - Induction of jasmonate signalling regulators MaMYC2s and their physical
      interactions with MaICE1 in methyl jasmonate-induced chilling tolerance in banana
      fruit.
AB  - MYC2, a basic helix-loop-helix (bHLH) transcription factor, is a key regulator in
      the activation of jasmonate (JA) response. However, the molecular details of MYC2
      involving in methyl jasmonate (MeJA)-induced chilling tolerance of fruit remain
      largely unclear. In the present work, two MYC2 genes, MaMYC2a and MaMYC2b, and
      one homolog of the inducer of the C-repeat-binding factor (CBF) gene, MaICE1 were
      isolated and characterized from banana fruit. MaMYC2s and MaICE1 were found to be
      all localized in the nucleus. In addition, the proline-rich domain (PRD) and the
      acidic domain (AD) in the N-terminus were important for the transcriptional
      activation of MaMYC2 in yeast cells. Unlike MaICE1's constitutive expression,
      MaMYC2a and MaMYC2b were induced rapidly following MeJA treatment during cold
      storage. Moreover, protein-protein interaction analysis confirmed that MaMYC2s
      interacted with MaICE1. The expression of ICE-CBF cold-responsive pathway genes
      including MaCBF1, MaCBF2, MaCOR1, MaKIN2, MaRD2 and MaRD5 was also significantly
      induced by MeJA. Taken together, our work provides strong evidence that MaMYC2 is
      involved in MeJA-induced chilling tolerance in banana fruit through physically
      interacting and likely functionally coordinating with MaICE1, revealing a novel
      mechanism for ICE1 in response to cold stress as well as during development of
      induced chilling tolerance.

PMID- 22651396
TI  - Morphogenetic and developmental functions of the Aspergillus nidulans homologues
      of the yeast bud site selection proteins Bud4 and Axl2.
AB  - The yeast bud site selection system represents a paradigm for understanding how
      fungal cells regulate the formation of a polarity axis. In Saccharomyces
      cerevisiae, Bud4 and Axl2 are components of the axial bud site marker. To address
      the possibility that these proteins regulate cellular morphogenesis in
      filamentous fungi, we have characterized homologues of Bud4 and Axl2 in
      Aspergillus nidulans. Our results show that Bud4 is involved in septum formation
      in both hyphae and developing conidiophores. Whereas Axl2 appears to have no
      obvious role in hyphal growth, it is required for the regulation of phialide
      morphogenesis during conidiation. In particular, Axl2 localizes to the phialide
      spore junction, where it appears to promote the recruitment of septins.
      Furthermore, the developmental regulators BrlA and AbaA control the expression of
      Axl2. Additional studies indicate that Axl2 is also involved in the regulation of
      sexual development, not only in A. nidulans, but also in the phylogenetically
      unrelated fungus Fusarium graminearum. Our results suggest that Axl2 plays a key
      role in phialide morphogenesis and/or function during conidiation in the
      aspergilli.

PMID- 22651395
TI  - Laparoscopic and open postchemotherapy retroperitoneal lymph node dissection in
      patients with advanced testicular cancer--a single center analysis.
AB  - BACKGROUND: The open approach represents the gold standard for postchemotherapy
      retroperitoneal lymph node dissection (O-PCLND) in patients with residual
      testicular cancer. We analyzed laparoscopic postchemotherapy retroperitoneal
      lymph node dissection (L-PCLND) and O-PCLND at our institution. METHODS: Patients
      underwent either L-PCLND (n = 43) or O-PCLND (n = 24). Categorical and continuous
      variables were compared using the Fisher exact test and Mann-Whitney U test
      respectively. Overall survival was evaluated with the log-rank test. RESULTS:
      Primary histology was embryonal cell carcinomas (18 patients), pure seminoma (2
      cases) and mixed NSGCTs (47 patients). According to the IGCCCG patients were
      categorized into "good", "intermediate" and "poor prognosis" disease in 55.2%,
      14.9% and 20.8%, respectively. Median operative time for L-PCLND was 212 min and
      232 min for O-PCLND (p = 0.256). Median postoperative duration of drainage and
      hospital stay was shorter after L-PCLND (0.0 vs. 3.5 days; p < 0.001 and 6.0 vs.
      11.5 days; p = 0.002). Intraoperative complications occurred in 21.7% (L-PCLND)
      and 38.0% (O-PCLND) of cases with 19.5% and 28.5% of Clavien Grade III
      complications for L-PCLND and O-PCLND, respectively (p = 0.224). Significant
      blood loss (>500 ml) was almost equally distributed (8.6% vs. 14.2%: p = 0.076).
      No significant differences were observed for injuries of major vessels and
      postoperative complications (p = 0.758; p = 0.370). Tumor recurrence occurred in
      8.6% following L-PCLND and in 14.2% following O-PCLND with a mean disease-free
      survival of 76.6 and 89.2 months, respectively. Overall survival was 83.3 and
      95.0 months for L-PCNLD and O-PCLND, respectively (p = 0.447). CONCLUSIONS: L
      PCLND represents a safe surgical option for well selected patients at an
      experienced center.

PMID- 22651541
TI  - Observational study of the outcomes and costs of initiating maintenance therapies
      in patients with moderate exacerbations of COPD.
AB  - BACKGROUND: There are limited data describing patients with moderate COPD
      exacerbations and evaluating comparative effectiveness of maintenance treatments
      in this patient population. The study examined COPD patients with moderate COPD
      exacerbations. COPD-related outcomes were compared between patients initiating
      fluticasone propionate-salmeterol 250/50 mcg (FSC) vs anticholinergics (ACs)
      following a moderate COPD exacerbation. METHODS: This retrospective observational
      study used a large administrative claims database (study period: 2003-2009) to
      identify and describe patients with an initial, moderate COPD exacerbation. A
      descriptive analysis of patients with moderate COPD exacerbations was done
      evaluating maintenance treatment rates, subsequent COPD exacerbation rates, and
      COPD-related costs during a 1-year period. A cohort analysis compared COPD
      exacerbation rates and associated costs during a variable-length follow-up period
      between patients initiating maintenance therapy with FSC or ACs. COPD
      exacerbations were reported as rate per 100 patient-years, and monthly costs were
      reported (standardized to USD 2009). COPD exacerbation rates between cohorts were
      evaluated using Cox proportional hazards models, and costs were analyzed using
      generalized linear models with log-link and gamma distribution. RESULTS: 21,524
      patients with a moderate COPD exacerbation were identified. Only 25% initiated
      maintenance therapy, and 13% had a subsequent exacerbation. Annual costs averaged
      $594 per patient. A total of 2,849 treated patients (FSC = 925; AC = 1,924) were
      eligible for the cohort analysis. The FSC cohort had a significantly lower rate
      of COPD exacerbations compared to the AC cohort (20.8 vs 32.8; P = 0.04). After
      adjusting for differences in baseline covariates, the FSC cohort had a 42%
      significantly lower risk of a COPD exacerbation (HR = 0.58; 95% CI: 0.38, 0.91).
      The FSC cohort incurred significantly higher adjusted pharmacy costs per patient
      per month by $37 (95% CI: $19, $72) for COPD-related medications vs the AC
      cohort. However, this increase was offset by a significant reduction in adjusted
      monthly medical costs per patient for the FSC vs the AC cohort ($82 vs $112; P <
      0.05). Total monthly COPD-related costs, as a result, did not differ between
      cohorts. CONCLUSIONS: Only a quarter of patients with a moderate COPD
      exacerbation were subsequently treated with maintenance therapy. Initiation of
      FSC among those treated was associated with better clinical and economic outcomes
      compared to AC.

PMID- 22651542
TI  - Modular click assembly of degradable capsules using polyrotaxanes.
AB  - A modular approach for the formation of degradable capsules using polyrotaxanes
      (PRXs) is described. The PRXs consist of alpha-cyclodextrin (alphaCD) and
      poly(ethylene glycol) (PEG), which are both biologically benign and the main
      degradation products of the capsules. The PRXs were equipped with three alkyne
      groups at their ends and could be successfully grafted to azide-functionalized
      silica particles (2.76 MUm diameter) using azide-alkyne click chemistry. The
      assembled PRXs were then cross-linked using a degradable linker. The cross-linked
      structure was sufficiently robust to allow the formation of capsules after
      dissolving the template silica particles. The formation of capsules of ca. 2 MUm
      diameter was verified by optical microscopy, TEM, and AFM imaging. The capsules
      were loaded with the chemotherapy drug doxorubicin (DOX) by conjugating it to the
      threaded alphaCDs via their free OH groups, while maintaining degradability of
      the capsules. Alkyne moieties at the surface of the cross-linked PRX architecture
      were available for further functionalization of the capsules, as is demonstrated
      by clicking on fluorescent PEG moieties. The DOX-loaded capsules were degraded
      within 90 min at 37  degrees C upon exposure to a 5 mM solution of glutathione in
      water.

PMID- 22651543
TI  - Sexual function and laparoscopic ventral rectopexy for complex rectocoele.
AB  - AIM: Laparoscopic ventral rectopexy (LVR) has recently been shown to be feasible,
      safe and efficient in restoring anatomy and improving rectal emptying in female
      patients presenting with a posterior pelvic floor prolapse. However, little is
      known about the sexual function of these patients. This study aimed to assess
      sexual activity in a group of patients referred for complex rectocoele and the
      consequences on sexual comfort of their treatment after LVR. METHOD: We
      prospectively assessed 41 consecutive patients who underwent LVR (either
      laparoscopic or robotic-assisted) for symptomatic complex rectocoele from January
      2009 to January 2010. We first identified sexually active patients in the cohort
      using a nonvalidated simplified questionnaire. The Brief Index Sexual Functioning
      for Women (BISF-W) questionnaire was used postoperatively to assess the impact of
      LVR on sexual function. Acceptability of the assessment of sexuality was also
      tested. The postoperative outcome of the sexually active patients was compared
      with data obtained from the French general population. RESULTS: Among 38 patients
      in whom a successful LVR had been performed (three conversions), 22 (57.9%) were
      sexually active preoperatively and 18 (47.4%) were sexually active
      postoperatively at a mean of 7+/-4.2months of follow-up (P=0.44). No de novo
      dyspareunia was reported. At baseline, 13 patients experienced dyspareunia
      compared with six after LVR (P=0.02). A significant improvement in dyspareunia
      was observed (seven patients vs two patients; P=0.03). 19 (86%) of the 22
      patients responded to the BISF-W questionnaire. The mean composite score was
      26.7+/-8.2, with 63.2% of patients estimating sexual activity as important or
      very important. Compared with a reference population, sexual comfort was similar
      in LVR patients (32.2+/-12.6 vs 26.7+/-8.2; P=0.14). CONCLUSION: Assessment of
      sexual function is accepted by the majority of patients suffering from pelvic
      floor disorders. In addition to the benefit on anatomical restoration and bowel
      function, LVR improves sexual function and dyspareunia in patients operated on
      for complex rectocoele.

PMID- 22651545
TI  - Rhenium-catalyzed regioselective synthesis of multisubstituted pyridines from
      beta-enamino ketones and alkynes via C-C bond cleavage.
AB  - A new method is described for the regioselective synthesis of multisubstituted
      pyridine derivatives. Treatment of N-acetyl beta-enamino ketones with alkynes in
      the presence of the rhenium catalyst, Re(2)(CO)(10), gives multisubstituted
      pyridines regioselectively. In this reaction, the N-acetyl moieties are important
      for the selective formation of the multisubstituted pyridines. This reaction
      proceeds via insertion of alkynes into a carbon-carbon single bond of beta
      enamino ketones, intramolecular nucleophilic cyclization, and elimination of
      acetic acid.

PMID- 22651546
TI  - Independent predictors of recovery of continence 3 months after robot-assisted
      laparoscopic radical prostatectomy.
AB  - PURPOSE: To investigate the factors that predict recovery of continence within 3
      months after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS:
      The charts of 452 patients who underwent RARP with a minimum follow-up period of
      3 months were collected prospectively and reviewed retrospectively. Urinary
      continence was determined using the self-administered validated Expanded Prostate
      Cancer Index Composite questionnaire during the routine follow-up visits.
      RESULTS: The overall continence rate 3 months after RARP was 79.9%. In an
      univariate logistic regression test, age<70 years, higher preoperative Sexual
      Health Inventory for Men (SHIM) score, lower clinical T(1) stage, lower biopsy
      and pathologic Gleason score, shorter operative time, lower estimated blood loss,
      smaller prostate volume (<40 cc) were associated with recovery of urinary
      continence within 3 months after RARP (P<0.05). In multivariate logistic
      regression analysis, younger age, higher SHIM score, lower clinical T(1) stage,
      lower body mass index (BMI), and smaller prostate volume were independent factors
      that predicted return of continence within 3 months after RARP (P<0.05).
      CONCLUSIONS: Younger age (<70 years), higher preoperative SHIM score, clinical
      T(1) stage, lower BMI, and smaller prostate volume (<40 cc) independently
      predicted recovery of continence within 3 months after RARP.

PMID- 22651548
TI  - Direct and stereoselective synthesis of 1,3-cis-3-
      arylsulphonaminodeoxydisaccharides and oligosaccharides.
AB  - The 3-aminoglycosides are ubiquitous in biologically important classes of
      glycoconjugates and naturally occurring oligosaccharides. Despite the rapid
      growth in the development of synthetic method of 3-amino glycosides, the current
      state-of-the art suffers from limited substrate scope, low yields, long reaction
      times, and anomeric mixtures. This work presents a novel direct method for the
      synthesis of 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides
      via alpha-selective glycosylation and hydroamination of glycal in a one-pot
      manner. This efficient multicomponent reaction methodology provides ready access
      to 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides and allows
      derivatization by variation of each component.

PMID- 22651549
TI  - Gender differences in brain activation on a mental rotation task.
AB  - Few neuroimaging studies have explored gender differences on mental rotation
      tasks. Most studies have utilized samples with both genders, samples mainly
      consisting of men, or samples with six or fewer females. Graduate students in
      science fields or liberal arts programs (20 males, 20 females) completed a mental
      rotation task during functional magnetic resonance imaging (fMRI). When a pair of
      cube figures was shown, the participant made a keypad response based on whether
      the pair is the same/similar or different. Regardless of gender, the bilateral
      middle frontal gyrus, bilateral intraparietal sulcus (IPS), and the left
      precuneus were activated when a subject tried to solve the mental rotation task.
      Increased activation in the right inferior frontal gyrus/middle frontal gyrus,
      the left precuneus/posterior cingulate cortex/cuneus region, and the left middle
      occipital gyrus was found for men as compared to women. Better accuracy and
      shorter response times were correlated with an increased activation in the
      bilateral intraparietal sulcus. No significant brain activity differences related
      to mental rotation were found between academic majors. These findings suggest
      that networks involved in visual attention appear to be more strongly activated
      in the mental rotation tasks in men as compared to women. It also suggests that
      men use a more automatic process when analyzing complex visual reasoning tasks
      while women use a more top-down process.

PMID- 22651550
TI  - Signalling profiles of circulating leucocytes in patients recovered from reactive
      arthritis.
AB  - OBJECTIVES: Reactive arthritis (ReA) is a sterile joint inflammation triggered by
      a remote infection and associated with human leucocyte antigen (HLA)-B27. Its
      pathogenesis is unknown, but abnormal response to microbial structures or
      endogenous inflammatory mediators may be involved. We studied responses in
      leucocyte signalling profiles in patients with previous ReA after a full
      recovery. METHOD: The study comprised 10 HLA-B27-positive healthy subjects with a
      history of Yersinia enterocolitica-triggered ReA (B27+ReA+) and 20 healthy
      reference subjects, of whom 10 carried HLA-B27 (B27+ReA-) and 10 did not (B27-ReA
      ). Phosphospecific fluorescent monoclonal antibodies and flow cytometry were used
      to determine activation of nuclear factor kappa B (NF-kappaB), signal transducers
      and activators of transcription (STATs) 1, 3, 5, and 6, and two mitogen-activated
      protein (MAP) kinases, p38 and extracellular signal-regulated kinase (ERK)1/2, in
      monocytes, lymphocytes, lymphocyte subsets, and neutrophils. B27+ReA+ and B27-ReA
      whole-blood samples were incubated with Yersinia with or without infliximab to
      study the role of tumour necrosis factor (TNF) in lymphocyte subset activation.
      Samples of the three subject groups were studied using soluble bacterial or
      endogenous stimuli. Fluorescence levels were determined as relative fluorescence
      units (RFU) and the proportion of positively fluorescing cells. RESULTS: The
      intracellular activation of circulating leucocytes in response to soluble stimuli
      was consistently comparable in B27+ReA+, B27+ReA-, and B27-ReA- subjects.
      Infliximab inhibited Yersinia-induced lymphocyte NF-kappaB phosphorylation
      similarly in B27+ReA+ and B27-ReA- groups. CONCLUSIONS: ReA susceptibility is not
      reflected in leucocyte signalling profiles elicited by phlogistic stimuli.
      However, the possibility remains that aberrations occur in response to
      combinations of stimuli, such as those associated with leucocyte adhesion.

PMID- 22651551
TI  - Unfavorable electrostatic and steric interactions in DNA polymerase beta E295K
      mutant interfere with the enzyme's pathway.
AB  - Mutations in DNA polymerase beta (pol beta) have been associated with
      approximately 30% of human tumors. The E295K mutation of pol beta has been linked
      to gastric carcinoma via interference with base excision repair. To interpret the
      different behavior of E295K as compared to wild-type pol beta in atomic and
      energetic detail, we resolve a binary crystal complex of E295K at 2.5 A and apply
      transition path sampling (TPS) to delineate the closing pathway of the E295K pol
      beta mutant. Conformational changes are important components in the enzymatic
      pathway that lead to and ready the enzyme for the chemical reaction. Our analyses
      show that the closing pathway of E295K mutant differs from the wild-type pol beta
      in terms of the individual transition states along the pathway, associated
      energies, and the active site conformation in the final closed form of the
      mutant. In particular, the closed state of E295K has a more distorted active site
      than the active site in the wild-type pol beta. In addition, the total energy
      barrier in the conformational closing pathway is 65 +/- 11 kJ/mol, much higher
      than that estimated for both correct (e.g., G:C) and incorrect (e.g., G:A) wild
      type pol beta systems (42 +/- 8 and 45 +/- 7 kJ/mol, respectively). In
      particular, the rotation of Arg258 is the rate-limiting step in the
      conformational pathway of E295K due to unfavorable electrostatic and steric
      interactions. The distorted active site in the closed relative to open state and
      the high energy barrier in the conformational pathway may explain in part why the
      E295K mutant is observed to be inactive. Interestingly, however, following the
      closing of the thumb but prior to the rotation of Arg258, the E295K mutant
      complex has a similar energy level as compared to the wild-type pol beta. This
      suggests that the E295K mutant may associate with DNA with similar affinity, but
      it may be hampered in continuing the process of chemistry. Supporting
      experimental data come from the observation that the catalytic activity of wild
      type pol beta is hampered when E295K is present: this may arise from the
      competition between E295K and wild-type enzyme for the DNA. These combined
      results suggest that the low insertion efficiency of E295K mutant as compared to
      wild-type pol beta may be related to a closed form distorted by unfavorable
      electrostatic and steric interactions between Arg258 and other key residues. The
      active site is thus less competent for proceeding to the chemical reaction, which
      may also involve a higher reaction barrier than the wild-type or may not be
      possible in this mutant. Our analysis also suggests further experiments for other
      mutants to test the above hypothesis and dissect the roles of steric and
      electrostatic factors on enzyme behavior.

PMID- 22651552
TI  - Comprehensive microarray-based analysis for stage-specific larval camouflage
      pattern-associated genes in the swallowtail butterfly, Papilio xuthus.
AB  - BACKGROUND: Body coloration is an ecologically important trait that is often
      involved in prey-predator interactions through mimicry and crypsis. Although this
      subject has attracted the interest of biologists and the general public, our
      scientific knowledge on the subject remains fragmentary. In the caterpillar of
      the swallowtail butterfly Papilio xuthus, spectacular changes in the color
      pattern are observed; the insect mimics bird droppings (mimetic pattern) as a
      young larva, and switches to a green camouflage coloration (cryptic pattern) in
      the final instar. Despite the wide variety and significance of larval color
      patterns, few studies have been conducted at a molecular level compared with the
      number of studies on adult butterfly wing patterns. RESULTS: To obtain a catalog
      of genes involved in larval mimetic and cryptic pattern formation, we constructed
      expressed sequence tag (EST) libraries of larval epidermis for P. xuthus, and P.
      polytes that contained 20,736 and 5,376 clones, respectively, representing one of
      the largest collections available in butterflies. A comparison with silkworm
      epidermal EST information revealed the high expression of putative blue and
      yellow pigment-binding proteins in Papilio species. We also designed a microarray
      from the EST dataset information, analyzed more than five stages each for six
      markings, and confirmed spatial expression patterns by whole-mount in situ
      hybridization. Hence, we succeeded in elucidating many novel marking-specific
      genes for mimetic and cryptic pattern formation, including pigment-binding
      protein genes, the melanin-associated gene yellow-h3, the ecdysteroid synthesis
      enzyme gene 3-dehydroecdysone 3b-reductase, and Papilio-specific genes. We also
      found many cuticular protein genes with marking specificity that may be
      associated with the unique surface nanostructure of the markings. Furthermore, we
      identified two transcription factors, spalt and ecdysteroid signal-related E75,
      as genes expressed in larval eyespot markings. This finding suggests that E75 is
      a strong candidate mediator of the hormone-dependent coordination of larval
      pattern formation. CONCLUSIONS: This study is one of the most comprehensive
      molecular analyses of complicated morphological features, and it will serve as a
      new resource for studying insect mimetic and cryptic pattern formation in
      general. The wide variety of marking-associated genes (both regulatory and
      structural genes) identified by our screening indicates that a similar strategy
      will be effective for understanding other complex traits.

PMID- 22651553
TI  - Collaborative learning about e-health for mental health professionals and service
      users in a structured anonymous online short course: pilot study.
AB  - BACKGROUND: Professionals are interested in using e-health but implementation of
      new methods is slow. Barriers to implementation include the need for training and
      limited awareness or experience. Research may not always convince mental health
      professionals (MHPs). Adding the 'voice' of mental health service users (MHSUs)
      in collaborative learning may help. Involving MHSUs in face-face education can be
      difficult. We had previously been unable to engage MHPs in online discussion with
      MHSUs. Here we assessed the feasibility of short online courses involving MHSUs
      and MHPs. METHODS: We ran three e-health courses, comprising live interactive
      webcast, week's access to a discussion forum, and final live interactive webcast.
      We recruited MHPs via posters, newsletters, and telephone from a local NHS trust,
      and online via mailing lists and personal contacts from NHS trusts and higher
      education. We recruited MHSUs via a previous project and an independent user
      involvement service. Participants were presented with research evidence about e
      health and asked to discuss topics using professional and lived experience.
      Feasibility was assessed through recruitment and attrition, participation, and
      researcher workloads. Outcomes of self-esteem and general self-efficacy (MHSUs),
      and Internet self-efficacy and confidence (MHPs) were piloted. RESULTS: Online
      recruiting was effective. We lost 15/41 from registration to follow-up but only
      5/31 that participated in the course failed to complete follow-up. Nineteen MHPs
      and 12 MHSUs took part and engaged with each other in online discussion. Feedback
      was positive; three-quarters of MHPs indicated future plans to use the Internet
      for practice, and 80% of MHSUs felt the course should be continued. Running three
      courses for 31 participants took between 200 to 250 hours. Before and after
      outcome measures were completed by 26/31 that participated. MHP Internet self
      efficacy and general Internet confidence, MHSU self-esteem and general self
      efficacy, all seemed reliable and seemed to show some increase. CONCLUSIONS:
      Collaborative learning between MHSUs and MHPs in a structured online anonymous
      environment over a one-week course is feasible, may be more practical and less
      costly than face-face methods, and is worthy of further study.

PMID- 22651555
TI  - Biomarkers and biomeasures: key enablers for pharmacokinetic-pharmacodynamic
      modeling in drug discovery and development.

PMID- 22651554
TI  - Ischemic preconditioning promotes intrinsic vascularization and enhances survival
      of implanted cells in an in vivo tissue engineering model.
AB  - Ischemic preconditioning (IPC) is a potent and effective means of protecting
      cells against ischemic injury. The protection has been demonstrated to involve
      release of paracrine factors that promote cell survival and angiogenesis, factors
      important for successful tissue engineering. The aim of the present study was to
      determine whether IPC of a vascular bed in vivo is an effective strategy to
      prepare it for tissue engineering with implanted cells. To test this hypothesis,
      an in vivo vascularized tissue engineering approach was employed, whereby
      polyacrylic chambers were placed around the femoral vessels of adult Sprague
      Dawley rats. IPC was induced by 3 cycles of 5 min femoral artery occlusion
      interspersed with 5-min periods of reperfusion. Rats subjected to IPC generated
      bigger tissue constructs at 7 and 28 days postimplantation of empty chambers
      (~50% increase in weight and volume, p<0.05). Morphometric counting of Masson
      trichrome stained tissue sections revealed significantly greater tissue construct
      volumes in ischemic preconditioned vascular beds at 7 and 28 days, increasing
      both fibrin matrix and vascularized tissue. Furthermore, morphometry of lectin
      labeled blood vessels indicated an increase in vascular volume in IPC tissue
      constructs (~100% increase vs. control, p<0.05). To investigate the
      cytoprotective effect of IPC, we implanted DiI-labeled neonatal rat
      cardiomyocytes in the chambers for 3 days, and IPC significantly reduced
      apoptosis of implanted cells as determined by the TUNEL assay and cleaved caspase
      3 immunostaining. Furthermore, IPC significantly increased the cardiac muscle
      volume and vascular volume at 28 days after implantation of cardiomyocytes. In
      conclusion, in vivo IPC promotes survival of implanted cardiomyocytes and is
      associated with enhanced angiogenesis. IPC may represent a new approach to
      optimize tissue engineering with implanted cells.

PMID- 22651557
TI  - Conference report: bioanalytical sessions at the 2011 Eastern Analytical
      Symposium.
AB  - The 2011 Eastern Analytical Symposium (EAS) and Exposition was held at the Garden
      State Exhibit Center in Somerset NJ, USA, 14-17 November and marked the 50th
      anniversary of EAS, with a theme of 'Celebrating Innovation in Analysis'. The
      technical program was rich in presentations relevant to bioanalytical sciences,
      covering biomarkers, proteomics/metabolomics, small molecule and protein LC-MS
      bioanalysis, immunogenicity and biological sample preparation. This conference
      report highlights some of the lectures and short courses of interest to
      bioanalysts at the 2011 EAS.

PMID- 22651558
TI  - Bioanalysis young investigator: Dajana Vuckovic.
AB  - Dajana currently has 21 peer-reviewed articles published or accepted for
      publication in top analytical chemistry journals including Analytical Chemistry
      and Angewandte Chemie International Edition. She has co-authored eight book
      chapters, and made 22 presentations at international conferences such as Pittcon
      and ASMS conferences. Dajana's commitment to excellence is also illustrated by
      the awards she has won to date, including a Postdoctoral Fellow Award offered by
      the Natural Science and Engineering Research Council of Canada (2010-2012) and
      the Douglas E Ryan Analytical Chemistry Student Award of the Canadian Society for
      Chemistry (2010). During her PhD in my group, Dajana excelled in very diverse
      areas of interest including the development of targeted LC-MS assays for drugs
      and metabolites, application of in vivo solid-phase microextraction (SPME) in
      mice and LC-MS metabolomics for the first time, and evaluation of a high
      throughput 96-well plate automated SPME system. Since her graduation from my
      group she has further extended her bioanalytical expertise to proteomics. I think
      Dajana's excellent research productivity, accomplishments to date, willingness to
      address complex bioanalytical challenges and extensive expertise in both small
      molecule and protein bioanalysis make her an excellent candidate for the
      Bioanalysis Young Investigator Award.

PMID- 22651559
TI  - Bioanalysis young investigator: Maria Rambla-Alegre.
AB  - Maria Rambla-Alegre obtained the European doctorate in March 2011, with the
      maximum qualification: Excellent "Cum Laude", and has already published 33
      articles in reputable scientific journals, presented 61 communications in
      international symposia, participated in nine research projects, as well as
      received several awards since 2006. Nowadays, Maria is contracted at Ghent
      University (Belgium) where she is completing a post-doc. During the time I have
      known her, I have frequently been impressed by her exceptional capabilities to
      quickly learn new skills to develop and validate new liquid chromatographic
      procedures, and by her constant initiative to bring together innovative
      analytical methods. Maria has always adopted a positive, critical view and shows
      eagerness to better herself. Besides her exceptional knowledge in LC, she has a
      sound scientific background in capillary electrophoresis, GC, sample preparation
      and optimization procedures that allows her to complement her investigations and
      has resulted in significant papers in the analytical chemistry field. Our
      research group has greatly benefited from Maria's capabilities, as can be seen in
      recent publications in the Journal of Chromatography A, Talanta, Analytical and
      Bioanalytical Chemistry and other specialized journals that directly represent
      her work, mainly as corresponding author. It is extremely remarkable that she has
      published a review of her PhD results. Not everyone has the possibility to
      publish it. This is a clear sign of the high quality of her research. Compared to
      other fellows that I have supervised, Maria is undoubtedly the best one. I can,
      beyond all doubt, give a score of 10/10 to the quality of her research activity.
      Finally, I would personally like to add that she is an outstanding, serious,
      independent thinker who is always well informed about the topics she tackles.
      Maria is also very friendly, a good worker and always willing to help others,
      which has been a most positive characteristic in creating a good atmosphere
      within the department. She is a bright and highly efficient person to work with.
      For all these reasons, I can only strongly recommend Maria to be awarded the
      Bioanalysis Young Investigator Award.

PMID- 22651560
TI  - Implication of free cholesterol in LC-MS response enhancement.
AB  - BACKGROUND: In the context of matrix effects in bioanalytical LC-MS/MS, a
      speculative link between free cholesterol, the recoveries of the compound from
      three common extraction procedures, and response enhancement was qualitatively
      investigated. RESULTS: Injections on-column of cholesterol both in solution and
      extracts, in conjunction with post-column infusion of three representative drugs,
      reveal a direct role in pronounced response enhancement for two out of three
      analytes, under one set of LC-MS/MS conditions, for the majority of typical
      plasma extraction procedures, where electrospray-based gaseous ion generation is
      used. CONCLUSION: Cholesterol has been shown to have a strong association with LC
      MS/MS response enhancement and ideally should be monitored during method
      development, reinforcing the reasoning behind minimizing SPE elution volumes and
      avoiding less selective means of sample preparation.

PMID- 22651561
TI  - Validation study of urinary metabolites as potential biomarkers for prostate
      cancer detection.
AB  - BACKGROUND: Urinary metabolomic profiles have recently drawn a lot of attention
      owing to a debate regarding their possible role as potential clinical markers for
      prostate cancer. In this study, levels of proline, kynurenine, uracil and
      glycerol-3-phosphate in 126 patients with genitourinary malignancies were
      analyzed using a validated method and compared with no evidence of malignancy.
      RESULTS: The statistical results showed that these biomarkers cannot
      differentiate prostate cancer from no evidence of malignancy or from other
      related cancer types, such as bladder cancer. In addition, there was no
      significant difference in biomarker levels for T1 stages, T2 stages and Gleason
      scores <7, >=7. From the correlation study, results showed/demonstrated that age
      or serum prostate-specific antigen levels do not influence these metabolite
      concentrations in urine. However, the strong correlation between these
      metabolites and urinary creatinine concentrations implies that their occurrence
      is mainly due to renal excretion. CONCLUSION: This detailed study shows that the
      aforementioned urinary metabolites are not reliable biomarkers for prostate
      cancer detection or for differentiating the aggressiveness of prostate cancer.

PMID- 22651562
TI  - Comparison of RP-HPLC columns used for determination of nucleoside metabolic
      patterns in urine of cancer patients.
AB  - BACKGROUND: Metabolic profiling allows the measurement of a large set of both
      known and unknown metabolites (such as nucleosides and nucleobases) present in a
      biological sample (e.g., urine). RESULTS: Separation of the isolated urinary
      nucleosides was performed on two connected Gemini C18 columns - 3 um pore size
      (50 cm total length) - at 55 degrees C using mobile-phase gradient elution. The
      Mann-Whitney U test was used to distinguish differences in the concentration of
      compounds in urine from urogenital cancer patients and healthy controls.
      Comparison of mean concentration values from the healthy and cancer groups
      revealed statistically significant differences (p < 0.01) for most of the
      metabolites studied (excluding m7G, m3C and A). Observed elevated levels of
      nucleosides mean concentrated values in urine in the case of cancer patients are
      between 1.5 and 2.0. CONCLUSION: These results verify the usefulness of the RP
      HPLC method to investigate the urinary pattern of normal and modified
      nucleosides.

PMID- 22651563
TI  - LC-MS/MS method for simultaneous estimation of candesartan and
      hydrochlorothiazide in human plasma and its use in clinical pharmacokinetics.
AB  - BACKGROUND: ATACAND HCT((r)) (candesartan cilexetil-hydrochlorothiazide [CAN
      HCTZ]) combines an angiotensin II receptor (type AT1) antagonist and a diuretic.
      Quantification of CAN and HCTZ in biological matrices has traditionally been
      difficult - developing a single method with the desired sensitivity has been the
      issue. RESULTS: A high-throughput bioanalytical method for the analysis of CAN
      and HCTZ in human plasma using liquid-liquid extraction and LC coupled to
      negative ion mode MS/MS has been developed and validated according to US FDA
      guidelines. The method uses 100 ul plasma and covers the calibration range 1-160
      ng/ml for CAN and 2-160 ng/ml for HCTZ for routine pharmacokinetic studies in
      humans. The intra- and inter-day precision values for CAN and HCTZ met the
      acceptance criteria. CAN and HCTZ were stable in a battery of stability studies
      (benchtop, autosampler and long-term). CONCLUSION: The advantages of the
      described technique included a single method with a shorter run time (2.5 min),
      simple extraction technique, LLOQ of 1 ng/ml for CAN and 2 ng/ml for HCTZ and
      lower sample volume (0.10 ml), which overcomes drawbacks of two single methods
      for each analyte, such as higher analysis time, LOQ and sample volume, as in
      previously published methods. The developed assay was applied to an oral
      pharmacokinetic study in humans.

PMID- 22651564
TI  - A novel UPLC-MS/MS method for simultaneous quantification of rhein, emodin,
      berberine and baicalin in rat plasma and its application in a pharmacokinetic
      study.
AB  - BACKGROUND: Dahuang Huanglian Xiexin Decoction (DHXD) is a classical formula in
      traditional Chinese medicines. In this study, a novel UPLC-MS/MS method was
      developed for the simultaneous quantification of rhein, emodin, berberine and
      baicalin, the major bioactive compounds of DHXD in rat plasma. RESULTS: The
      method possessed high sensitivity and ultrashort analysis time (7 min).
      Linearity, accuracy, precision and extraction recovery of four analytes were all
      satisfactory. The method was then successfully applied in a pharmacokinetic study
      of four bioactive components after a single oral administration of DHXD extract
      to rats. CONCLUSION: The method was applicable for simultaneous bioanalysis of
      rhein, emodin, berberine and baicalin.

PMID- 22651565
TI  - Validation and life-cycle management of a quantitative ligand-binding assay for
      the measurement of Nulojix((r)), a CTLA-4-Fc fusion protein, in renal and liver
      transplant patients.
AB  - BACKGROUND: Nulojix((r)) is a fusion protein composed of the Fc portion of a
      human IgG1 linked to the extracellular modified domain of CTLA-4. Nulojix differs
      from another Bristol Myers Squibb product, Orencia((r)) by two amino acids and
      was approved by the FDA on 15 June 2011 for the prophylaxis of organ rejection in
      adult patients receiving kidney transplant. RESULTS: A sandwich ELISA utilizing
      two monoclonal antibodies against CTLA-4 was employed for Nulojix quantification
      and pharmacokinetic analysis. At least 17 analysts have qualified on the assay
      and contributed to reportable results over the last 7 years. In-study accuracy
      and precision demonstrate suitable performance: %bias within -4 to 4%, %CV <=13%
      and total error within 6-15%. Incurred sample reanalysis was completed in
      applicable disease-state populations. The assay was automated and validated in
      additional clinical matrices (ascites and urine) and Nulojix quantification was
      validated in the presence of clinically relevant co-administered compounds. In
      2011, the biotinylation procedure was modified meriting a regression change
      (quadratic to 4-parameter logistic) and associated partial validation.
      CONCLUSION: This long-term pharmacokinetic program provides a good example of the
      dynamic clinical environment and adaptation requirements of ligand-binding
      assays.

PMID- 22651566
TI  - Perspectives on addressing ionization matrix effects in LC-MS bioanalysis.
AB  - Ionization matrix effects are one of the most difficult issues in LC-MS
      bioanalysis that are without a good and universal solution. Most people in the
      field are aware of it, but some are not sure how to deal with it. Many
      laboratories do not routinely assess matrix effects in method validation or
      substitute it with a different experiment that only indirectly and partially test
      matrix effects. Others, when matrix effects are mentioned, immediately link them
      with phospholipids and try to use means to remove them from the samples (e.g.,
      SPE), without understanding if the phospholipids can really impact the analytes.
      In this article, key issues related to matrix effects will be examined, and
      methods to address matrix effect problems will be evaluated for effectiveness and
      practicality.

PMID- 22651567
TI  - LC-MS metabolomics of polar compounds.
AB  - The metabolome is the complete set of small molecules coming from protein
      activity (anabolism and catabolism) in living systems. They have a broad range of
      chemical structures and physicochemical properties and therefore different
      analytical methodologies are necessary. Highly polar metabolites, such as sugars
      and most amino acids are not retained by conventional reversed-phase LC columns.
      Without sufficient retention, coelution may result in identification problems
      while the detection of compounds by MS at low concentrations may also be
      problematic due to ion suppression. In order to retain compounds based on their
      hydrophilicity, polar stationary phases and hydrophilic-interaction LC provide a
      complementary tool to reversed-phase LC for untargeted comprehensive metabolite
      fingerprinting. However, robustness of the methods is still limiting their
      applications. This review focuses on sample pretreatment, stationary phases,
      analytical methods and applications for polar compound analysis in biological
      matrices.

PMID- 22651568
TI  - Biomarker monitoring in sports doping control.
AB  - Biomarker monitoring can be considered a new era in the effort against doping.
      Opposed to the old concept in doping control of direct detection of a prohibited
      substance in a biological sample such as urine or blood, the new paradigm allows
      a personalized longitudinal monitoring of biomarkers that indicate non
      physiological responses independently of the used doping technique or substance,
      and may cause sanctioning of illicit practices. This review presents the
      development of biomarker monitoring in sports doping control and focuses on the
      implementation of the Athlete Biological Passport as the current concept of the
      World Anti Doping Agency for the detection of blood doping (hematological
      module). The scope of the article extends to the description of novel biomarkers
      and future concepts of application.

PMID- 22651570
TI  - In defense of adolescents: They really do use braces for the hours prescribed, if
      good help is provided. Results from a prospective everyday clinic cohort using
      thermobrace.
AB  - BACKGROUND: The effectiveness of bracing relies on the quality of the brace,
      compliance of the patient, and some disease factors. Patients and parents tend to
      overestimate adherence, so an objective assessment of compliance has been
      developed through the use of heat sensors. In 2010 we started the everyday
      clinical use of a temperature sensor, and the aim of this study is to present our
      initial results. METHODS:  POPULATION: A prospective cohort of 68 scoliosis
      patients that finished at least 4 months of brace treatment on March 31, 2011: 48
      at their first evaluation (79% females, age 14.2+/-2.4) and 20 already in
      treatment. TREATMENT: Bracing (SPoRT concept); physiotherapic specific exercises
      (SEAS School); team approach according to the SOSORT Bracing Management
      Guidelines.Methods. A heat sensor, "Thermobrace" (TB), has been validated and
      applied to the brace. The real (measured by TB) and referred (reported by the
      patient) compliances were calculated.Statistics. The distribution was not normal,
      hence median and 95% interval confidence (IC95) and non-parametric tests had to
      be used. RESULTS: Average TB use: 5.5+/-1.5 months. Brace prescription was 23
      hours/day (h/d) (IC95 18-23), with a referred compliance of 100% (IC95 70.7-100%)
      and a real one of 91.7% (IC95 56.6-101.7%), corresponding to 20 h/d (IC95 11-23).
      The more the brace was prescribed, the more compliant the patient was (94.8% in
      23 h/d vs. 73.2% in 18 h/d, P < 0.05). Sixty percent of the patients had at least
      90% compliance, and 45% remained within 1 hour of what had been prescribed. Non
      wearing days were 0 (IC95 0-12.95), and involved 29% of patients. CONCLUSION:
      This is the first study using a TB in a setting of respect for the SOSORT
      criteria for bracing, and it states that it is possible to achieve a very good
      compliance, even with a full time prescription, and better than what was
      previously reported (80% maximum). We hypothesize that the treating team (SOSORT
      criteria) plays a major role in our results. This study suggests that compliance
      is neither due to the type of treatment only nor to the patient alone. According
      to our experience, TB offers valuable insights and do not undermine the
      relationship with the patients.

PMID- 22651571
TI  - Dynamics of biological water: insights from molecular modeling of light
      scattering in aqueous trehalose solutions.
AB  - Extended depolarized light scattering (EDLS) measurements have been recently
      employed to investigate the dynamics of water solvating biological molecules,
      giving evidence of the presence of two different dynamical regimes among water
      molecules. An interpretation of EDLS has been proposed that provides an
      independent estimate of the retardation factor of slowdown with respect to fast
      water molecules and of the number of solvent molecules affected by this slowing
      down. Nevertheless this measure is an inherently complex one, due to the
      collective nature of the physical property probed. In the present work a
      molecular dynamics (MD) approach has been used to more deeply understand
      experimental results. Time correlation functions of the collective polarizability
      anisotropy have been calculated for the prototype disaccharide trehalose in
      aqueous solutions as a function of concentration. The unique capability of MD to
      disentangle the contributions to the dynamics arising from solute, solvent, and
      cross terms between the two allowed us to check the reliability of an
      interpretation that assumes a spectral separation of water and sugar dynamics, as
      well as to highlight the very presence of two distinct relaxation processes in
      water. The two processes have been attributed to the dynamics of bulk and
      hydration water, respectively. A retardation factor of ~5 and concentration
      dependent hydration numbers have been observed, in good agreement with
      experimental results [Paolantoni, M.; et al. J. Phys. Chem. B 2009, 113, 7874
      7878].

PMID- 22651572
TI  - Rapid cardiovascular effects of growth hormone treatment in short prepubertal
      children: impact of treatment duration.
AB  - OBJECTIVE: Previous studies show that growth hormone (GH) treatment increases
      cardiac dimensions in short children with GH deficiency (GHD) and has diverse
      cardiac effects in children with idiopathic short stature (ISS). This study was
      performed to assess the effect of GH on the cardiovascular system in short
      children with a broad range of GH secretion and GH sensitivity/responsiveness.
      DESIGN AND PATIENTS: In this prospective, multicentre study, short prepubertal
      children diagnosed with isolated GHD (89) or ISS (38) were followed during 2
      years of GH treatment. They were randomized to receive either a standard (43
      MUg/kg/day) or an individualized GH dose (range 17-100 MUg/kg/day) based on GH
      responsiveness estimated by a prediction model and distance to target height.
      Echocardiography, blood pressure and electrocardiography were performed at
      baseline, 3, 12 and 24 months. RESULTS: Left ventricular mass (LVM) indexed to
      body surface area increased significantly during 2 years of GH treatment in both
      GHD and ISS irrespective of randomized dose. This change was already apparent at
      3 months, when standard deviation scores (SDS) of wall thickness and diameter
      were increased. At 24 months, left ventricular diameter SDS remained increased,
      whereas myocardial thickness SDS returned to baseline values. There was no
      impairment of systolic or diastolic function. There was no correlation with
      treatment dose and LVM SDS at 24 months. CONCLUSIONS: Irrespective of GH status,
      there was a rapid increase in LVM during GH treatment in short children. At 3
      months, wall thickness and diameter were increased, whereas only diameter
      remained increased at 24 months.

PMID- 22651574
TI  - Peculiar field-dependent magnetic behavior of cyano-bridged coordination polymer
      Er(H2O)4[W(CN)8].
AB  - The two-dimensional cyano-bridged coordination polymer Er(H(2)O)(4)[W(CN)(8)]
      exhibits a magnetic transition at 12 K and an unusual field-dependent transition
      from short-range to ferromagnetic ordering.

PMID- 22651573
TI  - Immigrant women's experiences of maternity-care services in Canada: a protocol
      for systematic review using a narrative synthesis.
AB  - BACKGROUND: Canada's diverse society and statutory commitment to multiculturalism
      means that the synthesis of knowledge related to the health care experiences of
      immigrants is essential to realize the health potential for future Canadians.
      Although concerns about the maternity experiences of immigrants in Canada are
      relatively new, recent national guidelines explicitly call for tailoring of
      services to user needs. We are therefore assessing the experiences of immigrant
      women in Canada accessing maternity-care services. We are focusing on: 1)
      accessibility and acceptability (as an important dimension of access) to
      maternity-care services as perceived and experienced by immigrant women, and 2)
      the birth and postnatal outcomes of these women. METHODS: The aim of this study
      is to use a narrative synthesis, incorporating both a systematic review using
      narrative synthesis of reports of empirical research (qualitative, quantitative,
      and mixed-method designs), and a literature review of non-empirically based
      reports, both of which include 'grey' literature. The study aims to provide
      stakeholders with perspectives on maternity-care services as experienced by
      immigrant women. To achieve this, we are using integrated knowledge translation,
      partnering with key stakeholders to ensure topic relevancy and to tailor
      recommendations for effective translation into future policy and
      practice/programming. Two search phases and a three-stage selection process are
      being conducted (database search retrieved 1487 hits excluding duplicates) to
      provide evidence to contribute jointly to both the narrative synthesis and the
      non-empirical literature review. The narrative synthesis will be informed by the
      previous framework published in 2006 by Popay et al., using identified tools for
      each of its four elements. The non-empirical literature review will build upon
      the narrative-synthesis findings and/or identify omissions or gaps in the
      empirical research literature. The integrated knowledge translation plan will
      ensure that key messages are delivered in an audience-specific manner to optimize
      their effect on policy and practice change throughout the health service, and the
      public health, immigration and community sectors. DISCUSSION: Narrative-synthesis
      methods of systematic review facilitate understanding and acknowledgement of the
      broader influences of theoretical and contextual variables, such as race, gender,
      socioeconomic status, and geographical location. They also enable understanding
      of the shaping of differences between reported outcomes and study designs related
      to childbearing populations, and the development and implementation of maternity
      services and health interventions across diverse settings. PROSPERO REGISTRATION:
      Number 2185.

PMID- 22651575
TI  - Mechanism of the asymmetric activation of the MinD ATPase by MinE.
AB  - MinD is a component of the Min system involved in the spatial regulation of cell
      division. It is an ATPase in the MinD/ParA/Mrp deviant Walker A motif family
      which is within the P loop GTPase superfamily. Its ATPase activity is stimulated
      by MinE; however, the mechanism of this activation is unclear. MinD forms a
      symmetric dimer with two binding sites for MinE; however, a recent model
      suggested that MinE occupying one site was sufficient for ATP hydrolysis. By
      generating heterodimers with one binding site for MinE we show that one binding
      site is sufficient for stimulation of the MinD ATPase. Furthermore, comparison of
      structures of MinD and related proteins led us to examine the role of N45 in the
      switch I region. An asparagine at this position is conserved in four of the
      deviant Walker A motif subfamilies (MinD, chromosomal ParAs, Get3 and FleN) and
      we find that N45 in MinD is essential for MinE-stimulated ATPase activity and
      suggest that it is a key residue affected by MinE binding.

PMID- 22651577
TI  - Oxytocin and oxytocin receptor gene polymorphisms and risk for schizophrenia: a
      case-control study.
AB  - OBJECTIVES: Dysfunctions of the "social brain" belong to the core features of
      schizophrenia. The neurohormone oxytocin (OXT), mediated through its specific
      receptor (OXTR), is involved in the regulation of social behaviour and social
      cognition. Previous research has suggested a role of OXT system genes in
      disorders of social reciprocity. Preliminary evidence points to an association of
      peripheral OXT levels as well as OXT and OXTR gene polymorphisms with psychotic
      symptoms and treatment response in schizophrenia. This study aims to determine a
      possible contribution of OXT and OXTR genetic variations to schizophrenia
      susceptibility. METHODS: Using n = 406 individuals diagnosed with schizophrenia
      according to DSM-IV and n = 406 healthy controls matched for age and gender in a
      case-control design, two single nucleotide polymorphisms (SNPs) within the OXT
      gene (rs2740204, rs2740210) and four SNPs within the OXTR gene (rs53576,
      rs237880, rs237885, rs237902) that were previously investigated in other studies
      were genotyped. RESULTS: Chi(2)-testing suggested significant associations of
      OXTR SNPs rs53576(A > G) (P = 0.008) and rs237885(T > G) (P = 0.025) with a
      diagnosis of schizophrenia. Post-hoc ANCOVA revealed significant associations of
      OXTR SNPs rs53576 with general psychopathology and rs237902 with negative symptom
      scores in schizophrenic patients. CONCLUSIONS: Our findings support hypotheses
      about an involvement of oxytocinergic gene variants in schizophrenia
      vulnerability and warrant independent replication.

PMID- 22651576
TI  - Maternal smoking and the retinoid pathway in the developing lung.
AB  - BACKGROUND: Maternal smoking is a risk factor for pediatric lung disease,
      including asthma. Animal models suggest that maternal smoking causes defective
      alveolarization in the offspring. Retinoic acid signaling modulates both lung
      development and postnatal immune function. Thus, abnormalities in this pathway
      could mediate maternal smoking effects. We tested whether maternal smoking
      disrupts retinoic acid pathway expression and functioning in a murine model.
      METHODS: Female C57Bl/6 mice with/without mainstream cigarette smoke exposure (3
      research cigarettes a day, 5 days a week) were mated to nonsmoking males.
      Cigarette smoke exposure continued throughout the pregnancy and after
      parturition. Lung tissue from the offspring was examined by mean linear intercept
      analysis and by quantitative PCR. Cell culture experiments using the type II cell
      like cell line, A549, tested whether lipid-soluble cigarette smoke components
      affected binding and activation of retinoic acid response elements in vitro.
      RESULTS: Compared to tobacco-naive mice, juvenile mice with tobacco toxin
      exposure had significantly (P < 0.05) increased mean linear intercepts,
      consistent with an alveolarization defect. Tobacco toxin exposure significantly
      (P < 0.05) decreased mRNA and protein expression of retinoic acid signaling
      pathway elements, including retinoic acid receptor alpha and retinoic acid
      receptor beta, with the greatest number of changes observed between postnatal
      days 3-5. Lipid-soluble cigarette smoke components significantly (P < 0.05)
      decreased retinoic acid-induced binding and activation of the retinoic acid
      receptor response element in A549 cells. CONCLUSIONS: A murine model of maternal
      cigarette smoking causes abnormal alveolarization in association with altered
      retinoic acid pathway element expression in the offspring. An in vitro cell
      culture model shows that lipid-soluble components of cigarette smoke decrease
      retinoic acid response element activation. It is feasible that disruption of
      retinoic acid signaling contributes to the pediatric lung dysfunction caused by
      maternal smoking.

PMID- 22651669
TI  - North West England Perinatal and Paediatric HIV Network review of local
      guidelines used to manage infants born to HIV-positive women.

PMID- 22651670
TI  - Fusion of Na-ASP-2 with human immunoglobulin Fcgamma abrogates histamine release
      from basophils sensitized with anti-Na-ASP-2 IgE.
AB  - Na-ASP-2 is a major protein secreted by infective third-stage larvae (L3) of the
      human hookworm Necator americanus upon host entry. It was chosen as a lead
      vaccine candidate for its ability to elicit protective immune responses. However,
      clinical development of this antigen as a recombinant vaccine was halted because
      it caused allergic reactions among some of human volunteers previously infected
      with N. americanus. To prevent IgE-mediated allergic reactions induced by Na-ASP
      2 but keep its immunogenicity as a vaccine antigen, we designed and tested a
      genetically engineered fusion protein, Fcgamma/Na-ASP-2, composed of full-length
      Na-ASP-2 and truncated human IgG Fcgamma1 that targets the negative signalling
      receptor FcgammaRIIb expressed on pro-allergic cells. The chimeric recombinant
      Fcgamma/Na-ASP-2 protein was expressed in Pichia pastoris and shared the similar
      antigenicity as native Na-ASP-2. Compared to Na-ASP-2, the chimeric fusion
      protein efficiently reduced the release of histamine in human basophils
      sensitized with anti-Na-ASP-2 IgE obtained from individuals living in a hookworm
      endemic area. In dogs infected with canine hookworm, Fcgamma/Na-ASP-2 resulted in
      significantly reduced immediate-type skin reactivity when injected intradermally
      compared with Na-ASP-2. Hamsters vaccinated with Fcgamma/Na-ASP-2 formulated with
      Alhydrogel((r))  produced specific IgG that recognized Na-ASP-2 and elicited
      similar protection level against N. americanus L3 challenge as native Na-ASP-2.

PMID- 22651671
TI  - Ternifolide A, a new diterpenoid possessing a rare macrolide motif from Isodon
      ternifolius.
AB  - Ternifolide A (1), a new diterpenoid featuring a unique 10-membered lactone ring
      formed between C-6 and C-15, along with ternifolide B (2), a nor-diterpenoid, and
      ternifolide C (3) were isolated from the leaves of Isodon ternifolius. Both H-8
      and H-9 being alpha-orientations in compound 1 were found for the first time. The
      absolute configurations of 1 and 3 were confirmed by X-ray diffraction study.
      Compounds 1 and 3 were evaluated for their cytotoxicity.

PMID- 22651672
TI  - Phylogenomics supports microsporidia as the earliest diverging clade of sequenced
      fungi.
AB  - BACKGROUND: Microsporidia is one of the taxa that have experienced the most
      dramatic taxonomic reclassifications. Once thought to be among the earliest
      diverging eukaryotes, the fungal nature of this group of intracellular pathogens
      is now widely accepted. However, the specific position of microsporidia within
      the fungal tree of life is still debated. Due to the presence of accelerated
      evolutionary rates, phylogenetic analyses involving microsporidia are prone to
      methodological artifacts, such as long-branch attraction, especially when taxon
      sampling is limited. RESULTS: Here we exploit the recent availability of six
      complete microsporidian genomes to re-assess the long-standing question of their
      phylogenetic position. We show that microsporidians have a similar low level of
      conservation of gene neighborhood with other groups of fungi when controlling for
      the confounding effects of recent segmental duplications. A combined analysis of
      thousands of gene trees supports a topology in which microsporidia is a sister
      group to all other sequenced fungi. Moreover, this topology received increased
      support when less informative trees were discarded. This position of
      microsporidia was also strongly supported based on the combined analysis of 53
      concatenated genes, and was robust to filters controlling for rate heterogeneity,
      compositional bias, long branch attraction and heterotachy. CONCLUSIONS:
      Altogether, our data strongly support a scenario in which microsporidia is the
      earliest-diverging clade of sequenced fungi.

PMID- 22651673
TI  - What we know and what we need to learn about the treatment of dissociative
      disorders.
AB  - In this editorial, I briefly review research design issues and the current
      treatment research for dissociative disorders (DD), discuss the limitations and
      challenges of conducting treatment studies for patients with DD, and conclude by
      describing what I see as the first wave and second wave in the field of
      dissociation. Insurers and federally funded programs are increasingly requiring
      that treatment be empirically supported in order for treatment to be reimbursed.
      For example, psychoanalysis will no longer be reimbursed in The Netherlands
      because of what is perceived as a lack of empirical support. Other countries have
      also established standards about the treatments that have sufficient empirical
      support to merit government payment. I believe it is only a matter of time before
      it is common for patients with DD to be required to seek out empirically
      supported treatment if they want treatment to be reimbursed. We need to
      financially support treatment studies in order to develop a more solid empirical
      basis for the treatment of DD.

PMID- 22651675
TI  - Commentary on "Dissociation and psychosis in dissociative identity disorder and
      schizophrenia" (Laddis & Dell).

PMID- 22651674
TI  - Dissociation and psychosis in dissociative identity disorder and schizophrenia.
AB  - Dissociative symptoms, first-rank symptoms of schizophrenia, and delusions were
      assessed in 40 schizophrenia patients and 40 dissociative identity disorder (DID)
      patients with the Multidimensional Inventory of Dissociation (MID). Schizophrenia
      patients were diagnosed with the Structured Clinical Interview for the DSM-IV
      Axis I Disorders; DID patients were diagnosed with the Structured Clinical
      Interview for DSM-IV Dissociative Disorders-Revised. DID patients obtained
      significantly (a) higher dissociation scores; (b) higher passive-influence scores
      (first-rank symptoms); and (c) higher scores on scales that measure child voices,
      angry voices, persecutory voices, voices arguing, and voices commenting.
      Schizophrenia patients obtained significantly higher delusion scores than did DID
      patients. What is odd is that the dissociation scores of schizophrenia patients
      were unrelated to their reports of childhood maltreatment. Multiple regression
      analyses indicated that 81% of the variance in DID patients' dissociation scores
      was predicted by the MID's Ego-Alien Experiences Scale, whereas 92% of the
      variance in schizophrenia patients' dissociation scores was predicted by the
      MID's Voices Scale. We propose that schizophrenia patients' responses to the MID
      do not index the same pathology as do the responses of DID patients. We argue
      that neither phenomenological definitions of dissociation nor the current
      generation of dissociation instruments (which are uniformly phenomenological in
      nature) can distinguish between the dissociative phenomena of DID and what we
      suspect are just the dissociation-like phenomena of schizophrenia.

PMID- 22651677
TI  - Life history interviews with 11 boys diagnosed with attention
      deficit/hyperactivity disorder who had sexually offended: a sad storyline.
AB  - Little is known of the possible relationship between a diagnosis of attention
      deficit/hyperactivity disorder (ADHD) and sexually offensive behavior in
      adolescents. Our aim was to understand how adolescents with ADHD who had sexually
      offended described their childhood experiences and spoke about their diagnostic
      symptoms. The boys' early lives and relations were unpredictable, and emotional,
      physical, and sexual limits had been crossed. However, many boys saw themselves
      or their diagnosis, rather than their parents, school, or "society," as the
      underlying cause of their behavior. They used different strategies, for example
      repressing memories or regarding traumatic experiences as normal, to manage their
      lives. Most boys had difficulty with emotions and expressed sadness or
      frustration through anger. They spoke of being inattentive and restless in school
      and impulsive before and during their sexual offenses. The psychiatric assessment
      was described as a "messy" experience that strengthened their belief that
      something was wrong with them. Some had incorporated neuropsychiatric language
      into otherwise limited vocabularies and tended to use their diagnostic symptoms
      to excuse their offenses. The focus in the assessment on the boys themselves and
      their behaviors may darken their understandings of themselves, their experiences
      of abuse, and the offenses they have committed. Further research is needed into
      the possible consequences of a diagnosis of ADHD on adolescents' self-image and
      sense of self-control.

PMID- 22651678
TI  - Coping strategies in female survivors of childhood sexual abuse from two Canadian
      and two New Zealand cultural groups.
AB  - Individuals from some minority cultures are at greater risk of experiencing
      childhood sexual abuse (CSA) and are also at heightened risk of negative outcomes
      from abuse. Coping strategies, which may mediate the relationship between CSA and
      outcomes, are also impacted by culture. This study examined the use of coping
      strategies in female survivors of CSA across 4 cultural groupings from 2
      countries-86 European Canadians, 40 Native Canadians, 129 European New
      Zealanders, and 35 Maori New Zealanders-who all completed the Coping Responses
      Inventory. The 4 groups differed significantly on 7 of the 8 Coping Responses
      Inventory scales (Logical Analysis, Positive Reappraisal, Problem Solving,
      Cognitive Avoidance, Acceptance or Resignation, Seeking Alternative Rewards,
      Emotional Discharge). Whereas New Zealanders differed significantly from
      Canadians (p<.001), Europeans did not differ significantly from indigenous
      cultural groups, nor did nationality and culture grouping interact (p>.05). The
      profile of coping in New Zealand Europeans was relatively flat, with average
      scores across coping types close to the mean of the t-score distribution. Maori
      New Zealanders produced a similar profile, with only slight increases on 2 scales
      of avoidant coping. The findings raise questions about the extent to which
      generalizations can be made about there being either a "Western/European" culture
      or a particular "indigenous" culture. This in turn also raises the issue of
      whether cross-validation and replication of findings are needed if the findings
      are to be applied outside of the country in which the data were gathered.

PMID- 22651679
TI  - Parallels in sources of trauma, pain, distress, and suffering in humans and
      nonhuman animals.
AB  - It is widely accepted that animals often experience pain and distress as a result
      of their use in scientific experimentation. However, unlike human suffering, the
      wide range of acute, recurrent, and chronic stressors and trauma on animals is
      rarely evaluated. In order to better understand the cumulative effects of
      captivity and laboratory research conditions on animals, we explore parallels
      between human experiences of pain and psychological distress and those of animals
      based on shared brain structures and physiological mechanisms. We review
      anatomical, physiological, and behavioral similarities between humans and other
      animals regarding the potential for suffering. In addition, we examine
      associations between research conditions and indicators of pain and distress. We
      include 4 case studies of common animal research protocols in order to illustrate
      incidental and experimental factors that can lead to animal suffering. Finally,
      we identify parallels between established traumatic conditions for humans and
      existing laboratory conditions for animals.

PMID- 22651680
TI  - Peritraumatic dissociation as a mediator of peritraumatic distress and PTSD: a
      retrospective, cross-sectional study.
AB  - The objective of the present article was to examine the mediational significance
      of peritraumatic dissociation in the relationship between peritraumatic distress
      and posttraumatic stress disorder (PTSD). A total of 71 individuals with spinal
      cord injuries completed interviews and questionnaires measuring PTSD
      symptomatology, peritraumatic dissociation, and peritraumatic distress.
      Peritraumatic dissociation was found to partially mediate the relationship
      between peritraumatic distress and PTSD symptomatology. These findings provide
      support for the hypothesis that peritraumatic distress and peritraumatic
      dissociation significantly impact PTSD severity. The findings also support the
      hypothesis that peritraumatic dissociation is provoked by peritraumatic distress.
      The results further indicate that although peritraumatic dissociation seems to be
      a significant risk factor for PTSD, it is not necessary for the development of
      PTSD; the presence of peritraumatic distress may be sufficient. These findings
      highlight the importance of investigating peritraumatic reactions after a
      traumatic event in order to identify individuals at risk for developing PTSD.
      Such a practice may help prevent the development of chronic conditions.

PMID- 22651681
TI  - Dancing with the Muses: dissociation and flow.
AB  - This study investigated dissociative psychological processes and flow
      (dispositional and state) in a group of professional and pre-professional dancers
      (n=74). In this study, high scores for global (Mdn=4.14) and autotelic (Mdn=4.50)
      flow suggest that dancing was inherently integrating and rewarding, although
      17.6% of the dancers were identified as possibly having clinical levels of
      dissociation (Dissociative Experiences Scale-Taxon cutoff score>=20). The results
      of the multivariate analysis of variance indicated that subjects with high levels
      of dissociation had significantly lower levels of global flow (p<.05). Stepwise
      linear regression analyses demonstrated that dispositional flow negatively
      predicted the dissociative constructs of depersonalization and taxon (p<.05) but
      did not significantly predict the variance in absorption/imagination (p>.05). As
      hypothesized, dissociation and flow seem to operate as different mental
      processes.

PMID- 22651684
TI  - Nonadiabatic dynamics of photoinduced proton-coupled electron transfer:
      comparison of explicit and implicit solvent simulations.
AB  - Theoretical approaches for simulating the ultrafast dynamics of photoinduced
      proton-coupled electron transfer (PCET) reactions in solution are developed and
      applied to a series of model systems. These processes are simulated by
      propagating nonadiabatic surface hopping trajectories on electron-proton vibronic
      surfaces that depend on the solute and solvent nuclear coordinates. The PCET
      system is represented by a four-state empirical valence bond model, and the
      solvent is treated either as explicit solvent molecules or as a dielectric
      continuum, in which case the solvent dynamics is described in terms of two
      collective solvent coordinates corresponding to the energy gaps associated with
      electron and proton transfer. The explicit solvent simulations reveal two
      distinct solvent relaxation time scales, where the faster time scale relaxation
      corresponds to librational motions of solvent molecules in the first solvation
      shell, and the slower time scale relaxation corresponds to the bulk solvent
      dielectric response. The charge transfer dynamics is strongly coupled to both the
      fast and slow time scale solvent dynamics. The dynamical multistate continuum
      theory is extended to include the effects of two solvent relaxation time scales,
      and the resulting coupled generalized Langevin equations depend on parameters
      that can be extracted from equilibrium molecular dynamics simulations. The
      implicit and explicit solvent approaches lead to qualitatively similar charge
      transfer and solvent dynamics for model PCET systems, suggesting that the
      implicit solvent treatment captures the essential elements of the nonequilibrium
      solvent dynamics for many systems. A combination of implicit and explicit solvent
      approaches will enable the investigation of photoinduced PCET processes in a
      variety of condensed phase systems.

PMID- 22651686
TI  - TILLING in extremis.
AB  - Targeting induced local lesions in genomes (TILLING), initially a functional
      genomics tool in model plants, has been extended to many plant species and become
      of paramount importance to reverse genetics in crops species. Because it is
      readily applicable to most plants, it remains a dominant non-transgenic method
      for obtaining mutations in known genes. The process has seen many technological
      changes over the last 10 years; a major recent change has been the application of
      next-generation sequencing (NGS) to the process, which permits multiplexing of
      gene targets and genomes. NGS will ultimately lead to TILLING becoming an in
      silico procedure. We review here the history and technology in brief, but focus
      more importantly on recent developments in polyploids, vegetatively propagated
      crops and the future of TILLING for plant breeding.

PMID- 22651685
TI  - Factor VII light chain-targeted lidamycin shows intensified therapeutic efficacy
      for liver cancer.
AB  - The overexpression of tissue factor (TF) observed in numerous cancer cells and
      clinical samples of human cancers makes TF an ideal target for cancer therapy.
      The purpose of this study is to develop a TF-targeting energized fusion protein
      hlFVII-LDP-AE, which is composed of a human Factor VII light chain (hlFVII) as
      the targeting domain conjugated to the cytotoxic antibiotic lidamycin (LDM, LDP
      AE) as the effector domain. The potential efficacy of hlFVII-LDP-AE for cancer
      therapy was tested in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) and colony formation assays and in vivo with a
      BALB/c nude mouse xenograft model of human liver cancer line HepG2. The
      inhibitory concentration (IC(50)) value of hlFVII-LDP-AE varied from 0.15 to 0.64
      nM for the various human tumor lines. hlFVII-LDP-AE showed a tumor growth
      inhibition rate of 90.6% at the dose of 0.6 mg/kg in in vivo animal experiments.
      The mechanism through which hlFVII-LDP-AE inhibits tumor growth also was
      determined by Hoechst 33342 staining and Tdt-mediated dUTP nick-end labeling
      (TUNEL) assay. hlFVII-LDP-AE causes tumor cell death through inducing chromatin
      condensation and cleavage of genomic DNA. These findings suggest that the hlFVII
      LDP-AE protocol is efficacious and tolerated in the mouse model of human liver
      cancer HepG2 and has clinical applicability for treating cancer patients.

PMID- 22651687
TI  - Cardiac tamponade: contrast reflux as an indicator of cardiac chamber
      equalization.
AB  - BACKGROUND: Traumatic hemopericardium remains a rare entity; it does however
      commonly cause cardiac tamponade which remains a major cause of death in
      traumatic blunt cardiac injury. OBJECTIVES: We present a case of blunt chest
      trauma complicated by cardiac tamponade causing cardiac chamber equalization
      revealed by reflux of contrast. CASE REPORT: A 29-year-old unidentified male
      suffered blunt chest trauma in a motor vehicle collision. Computed tomography
      (CT) demonstrated a periaortic hematoma and hemopericardium. Significant contrast
      reflux was seen in the inferior vena cava and hepatic veins suggesting a change
      in cardiac chamber pressures. After intensive treatment including cardiac massage
      this patient expired of cardiac arrest. CONCLUSION: Reflux of contrast on CT
      imaging can be an indicator of traumatic cardiac tamponade.

PMID- 22651688
TI  - Pharmacological normalization of circulation after acute brain death.
AB  - BACKGROUND: Circulatory instability is a serious problem after brain death in
      organ donors. The hypotension is often counteracted with infusion of large
      amounts of crystalloid solutions, which may impair lung function leading to
      rejection of the lungs as donor organs. The aim was to show that the circulation
      can be normalized pharmacologically for 24 h in pigs after total removal of the
      brain and brainstem by decapitation (between C2 and C3). METHODS: Twenty-four 40
      kg pigs (n = 8 * 3) were included: non-decapitated, decapitated, and decapitated
      with pharmacological treatment. All animals got the same basal fluid supply and
      ventilation. The pharmacological treatment consisted of the neuronal monoamine
      reuptake blocker cocaine and low doses of noradrenaline and adrenaline.
      Desmopressin, triiodothyroxine, thyroxine and cortisol were also given. RESULTS:
      After decapitation, a catecholamine storm occurred, with an increase of
      noradrenaline and adrenaline by a factor of 79 and 298, respectively. Thirty
      minutes later, the pigs were hypotensive. The median time to the aortic pressure
      that was less than 40 mmHg was 9:09 h (range 5:50 to 22:01). After 6 h, the
      concentration of thyroid hormones and cortisol was significantly reduced. With
      pharmacological treatment of decapitated animals, the aortic pressure, renal
      blood flow, creatinine, urine production, liver function and blood gases did not
      differ significantly from the non-decapitated control animals. CONCLUSION:
      Pharmacological substitution of pituitary gland function, blockade of peripheral
      catecholamine neuronal reuptake and low doses of catecholamines normalize
      circulation in decapitated pigs throughout a 24-h observation period, whereas
      untreated decapitated pigs all develop severe circulatory collapse within 12 h.

PMID- 22651689
TI  - Expression patterns of histone deacetylases in experimental stroke and potential
      targets for neuroprotection.
AB  - 1. Histone deacetylase (HDAC) inhibitors exert neuroprotection in both cellular
      and animal models of ischaemic stroke. However, which HDAC isoform (or isoforms)
      mediates this beneficial effect has not yet been determined. 2. In the present
      study, gene levels of the HDAC isoforms were determined in the mouse cortex using
      reverse transcription-polymerase chain reaction (RT-PCR), whereas changes in the
      expression of individual zinc-dependent HDAC family members were evaluated by
      western blotting, 3, 12, 24 and 48 h after cerebral ischaemia induced by
      transient middle cerebral artery occlusion in male Kunming mice. 3. The HDAC
      isoforms HDAC1-11 were all expressed in the mouse cortex and differentially
      affected by cerebral ischaemia. Notably, there was a substantial increase in
      HDAC3, HDAC6 and HDAC11 expression during the early phases of experimental
      stroke, indicating their contribution to stroke pathogenesis. Furthermore,
      induction of HDAC3 and HDAC6 in cortical neurons by ischaemic stroke was
      confirmed in vivo and in vitro using double-labelled immunostaining and RT-PCR,
      respectively. Therefore, small hairpin (sh) RNAs were used to selectively knock
      down HDAC3 or HDAC6. This knockdown appreciably promoted the survival of cortical
      neurons subjected to oxygen and glucose deprivation. 4. The findings of the
      present study demonstrate the expression patterns of HDAC isoforms during
      experimental ischaemic stroke. Furthermore, HDAC3 and HDAC6 were identified as
      potential mediators in the neurotoxicity of ischaemic stroke, suggesting that
      specific therapeutic approaches may be considered according to HDAC subtype.

PMID- 22651690
TI  - Rhenium(I) tricarbonyl complexes of 5,10,15,20-tetraphenyl-21-thia and 21
      oxaporphyrins.
AB  - The hexa-coordinated rhenium(I) tricarbonyl complexes of 5,10,15,20-tetraphenyl
      21-thiaporphyrin 1 and 5,10,15,20-tetraphenyl-21-oxaporphyrin 2 have been
      synthesized by thermal reaction of corresponding free base porphyrin with
      Re(2)(CO)(10). The compounds 1 and 2 are characterized by HR-MS mass, (1)H, and
      (13)C NMR, FTIR, UV-vis, and electrochemical techniques and the structures are
      determined by X-ray single crystal analysis. The X-ray analysis revealed
      different coordination behavior of Re(CO)(3) with 21-thiaporphyrin and 21
      oxaporphyrin. Interestingly, the Re(CO)(3) coordinates to two of the three inner
      nitrogens and one sulfur instead of three inner nitrogens as generally expected
      to produce unique compound 1 whereas it coordinates to three inner nitrogens but
      not with furan oxygen to form compound 2. The 21-thiaporphyrin ring is more
      distorted in compound 1 compared to 21-oxaporphyrin ring in compound 2 on
      complexation with Re(CO)(3). The presence of three carbonyl groups in compounds 1
      and 2 are verified by (13)C NMR and IR spectroscopy. The absorption spectra of
      compounds 1 and 2 showed ill-defined Q-bands along with broad Soret band and the
      extinction coefficients are much lower than their corresponding free base
      porphyrins. The compounds 1 and 2 showed two reversible porphyrin ring based
      reductions supporting their electron deficient nature. The compound 1 is very
      stable under protonation conditions, and the protonation occurs at the
      uncoordinated pyrrole ring whereas the compound 2 undergoes decomplexation under
      same conditions. Furthermore, compound 1 showed the fluxional behavior in
      coordination mode of binding in solution.

PMID- 22651691
TI  - Predicting protein-ATP binding sites from primary sequence through fusing bi
      profile sampling of multi-view features.
AB  - BACKGROUND: Adenosine-5'-triphosphate (ATP) is one of multifunctional nucleotides
      and plays an important role in cell biology as a coenzyme interacting with
      proteins. Revealing the binding sites between protein and ATP is significantly
      important to understand the functionality of the proteins and the mechanisms of
      protein-ATP complex. RESULTS: In this paper, we propose a novel framework for
      predicting the proteins' functional residues, through which they can bind with
      ATP molecules. The new prediction protocol is achieved by combination of sequence
      evolutional information and bi-profile sampling of multi-view sequential features
      and the sequence derived structural features. The hypothesis for this strategy is
      single-view feature can only represent partial target's knowledge and multiple
      sources of descriptors can be complementary. CONCLUSIONS: Prediction performances
      evaluated by both 5-fold and leave-one-out jackknife cross-validation tests on
      two benchmark datasets consisting of 168 and 227 non-homologous ATP binding
      proteins respectively demonstrate the efficacy of the proposed protocol. Our
      experimental results also reveal that the residue structural characteristics of
      real protein-ATP binding sites are significant different from those normal ones,
      for example the binding residues do not show high solvent accessibility
      propensities, and the bindings prefer to occur at the conjoint points between
      different secondary structure segments. Furthermore, results also show that
      performance is affected by the imbalanced training datasets by testing multiple
      ratios between positive and negative samples in the experiments. Increasing the
      dataset scale is also demonstrated useful for improving the prediction
      performances.

PMID- 22651693
TI  - The 2011 model of the clinical practice of emergency medicine.
AB  - The 2011 Model of the Clinical Practice of Emergency Medicine.

PMID- 22651695
TI  - Access to preventive care by immigrant populations.
AB  - Many immigrant populations lack access to primary health care. A recently
      published study on cholesterol screening among immigrant populations in the US
      found disparities in cholesterol screening in those originating from Mexico,
      largely due to limited access to healthcare. This inverse care affects immigrants
      in many destination countries despite their greater health need.Please see
      related article: http://www.equityhealthj.com/content/11/1/22.

PMID- 22651694
TI  - Adipocyte induction of preadipocyte differentiation in a gradient chamber.
AB  - Adipose tissue expansion involves enlargement of mature adipocytes and the
      formation of new adipocytes through the differentiation of locally resident
      preadipocytes. Factors released by the enlarged adipocytes are potential cues
      that induce the differentiation of the preadipocytes. Currently, there are
      limited options to investigate these cues in isolation from confounding systemic
      influences. A gradient generating microfluidic channel-based cell culture system
      was designed to enable solution patterning, while supporting long-term culture
      and differentiation of preadipocytes. Solution patterning was confirmed by
      selectively staining a fraction of uniformly seeded preadipocytes. An adipogenic
      cocktail gradient was used to induce the differentiation of a fraction of
      uniformly seeded preadipocytes and establish a spatially defined coculture of
      adipocytes and preadipocytes. Varying the adipogenic cocktail gradient generated
      cocultures of preadipocytes and adipocytes with different compositions. Transient
      application of the cocktail gradient, followed by basal medium treatment showed a
      biphasic induction of differentiation. The two phases of differentiation
      correlated with a spatial gradient in adipocyte size. Our results provide in
      vitro data supporting the size-dependent release of preadipocyte differentiation
      factors by enlarged adipocytes. Prospectively, the coculture system developed in
      this study could facilitate controlled, yet physiologically meaningful studies on
      paracrine interactions between adipocytes and preadipocytes during adipose tissue
      development.

PMID- 22651696
TI  - Vapor phase polymerization of EDOT from submicrometer scale oxidant patterned by
      dip-pen nanolithography.
AB  - Some of the most exciting recent advances in conducting polymer synthesis have
      centered around the method of vapor phase polymerization (VPP) of thin films.
      However, it is not known whether the VPP process can proceed using significantly
      reduced volumes of oxidant and therefore be implemented as part of
      nanolithography approach. Here, we present a strategy for submicrometer scale
      patterning of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) via
      in situ VPP. Attolitre (10(-18) L) volumes of oxidant "ink" are controllably
      deposited using dip-pen nanolithography (DPN). DPN patterning of the oxidant ink
      is facilitated by the incorporation of an amphiphilic block copolymer thickener,
      an additive that also assists with stabilization of the oxidant. When exposed to
      EDOT monomer in a VPP chamber, each deposited feature localizes the synthesis of
      conducting PEDOT structures of several micrometers down to 250 nm in width. PEDOT
      patterns are characterized by atomic force microscopy (AFM), conductive AFM, two
      probe electrical measurement, and micro-Raman spectroscopy, evidencing in situ
      vapor phase synthesis of conducting polymer at a scale (picogram) which is much
      smaller than that previously reported. Although the process of VPP on this scale
      was achieved, we highlight some of the challenges that need to be overcome to
      make this approach feasible in an applied setting.

PMID- 22651697
TI  - Degree of vaporization in bipolar and monopolar resection.
AB  - PURPOSE: To compare the in vitro degree of vaporization in bipolar and monopolar
      resection. MATERIALS AND METHODS: Using either a bipolar system or a monopolar
      system, samples of chicken muscle and lamb kidney were resected in an isolated
      basin and then desiccated in an incubator. The percentual degree of vaporization
      for each sample was obtained as a difference between the total fresh weight of
      the sample and the calculated fresh weights of the resected tissue and remains.
      RESULTS: Reference samples showed that the water content was 73% in muscle and
      77% in kidney. More muscle (mean 52%) than kidney (32%; P<0.0001) tissue was
      vaporized. The fraction of vaporized tissue was significantly higher in the
      bipolar technique. In muscle, the differences between monopolar and bipolar were
      17% (P<0.05) and 26% (P<0.001), respectively, depending on the type of irrigation
      used. For kidney, the differences were 27% (P<0.01) and 34% (P<0.01),
      respectively. Further exploration of the degree of vaporization when using the
      bipolar resection showed that the choice of loop (P<0.0001), fluid (P<0.03), and
      tissue (P<0.0001) were all independently associated with the degree of
      vaporization. CONCLUSIONS: This study indicated that vaporization removes 50%
      more tissue than the weight of the resected tissue during conventional tissue
      resection. Bipolar standard loop resection resulted in a significantly higher
      degree of vaporization in both muscle and kidney than did monopolar technique.
      Bipolar resection worked satisfactorily in Ringer's acetate.

PMID- 22651699
TI  - Efficient a priori identification of drug resistant mutations using Dead-End
      Elimination and MM-PBSA.
AB  - Active site mutations that disrupt drug binding are an important mechanism of
      drug resistance. Computational methods capable of predicting resistance a priori
      are poised to become extremely useful tools in the fields of drug discovery and
      treatment design. In this paper, we describe an approach to predicting drug
      resistance on the basis of Dead-End Elimination and MM-PBSA that requires no
      prior knowledge of resistance. Our method utilizes a two-pass search to identify
      mutations that impair drug binding while maintaining affinity for the native
      substrate. We use our method to probe resistance in four drug-target systems:
      isoniazid-enoyl-ACP reductase (tuberculosis), ritonavir-HIV protease (HIV),
      methotrexate-dihydrofolate reductase (breast cancer and leukemia), and gleevec
      ABL kinase (leukemia). We validate our model using clinically known resistance
      mutations for all four test systems. In all cases, the model correctly predicts
      the majority of known resistance mutations.

PMID- 22651698
TI  - Pharmacologic venous thromboembolism prophylaxis after traumatic brain injury: a
      critical literature review.
AB  - Despite the frequency and morbidity of venous thromboembolism (VTE) development
      after traumatic brain injury (TBI), no national standard of care exists to guide
      TBI caregivers for the use of prophylactic anticoagulation. Fears of iatrogenic
      propagation of intracranial hemorrhage patterns have led to a dearth of research
      in this field, and it is only relatively recently that studies dedicated to this
      question have been performed. These have generally been limited to retrospective
      and/or observational studies in which patients are classified in a binary fashion
      as having the presence or absence of intracranial blood. This methodology does
      not account for the fact that smaller injury patterns stabilize more rapidly, and
      thus may be able to safely tolerate earlier initiation of prophylactic
      anticoagulation than larger injury patterns. This review seeks to critically
      assess the literature on this question by examining the existing evidence on the
      safety and efficacy of pharmacologic VTE prophylaxis in the setting of elective
      craniotomy (as this is the closest model available from which to extrapolate) and
      after TBI. In doing so, we critique studies that approach TBI as a homogenous or
      a heterogenous study population. Finally, we propose our own theoretical protocol
      which stratifies patients into low, moderate, and high risk for the likelihood of
      natural progression of their hemorrhage pattern, and which allows one to tailor a
      unique VTE prophylaxis regimen to each individual arm.

PMID- 22651700
TI  - Highly enantioselective chlorination of beta-keto esters and subsequent S(N)2
      displacement of tertiary chlorides: a flexible method for the construction of
      quaternary stereogenic centers.
AB  - Highly enantioselective chlorination of beta-oxo esters and subsequent
      stereospecific substitution of tertiary chlorides are described. Enantioselective
      chlorination of beta-keto esters and malonates was performed using a chiral Lewis
      acid catalyst prepared from Cu(OTf)(2) and the newly developed spirooxazoline
      ligand 2 to yield the desired alpha-chlorinated products with high
      enantioselectivity (up to 98% ee). Nucleophilic substitution of the resulting
      chlorides proceeded smoothly to afford a variety of chiral molecules such as
      alpha-amino, alpha-alkylthio, and alpha-fluoro esters, without loss of
      enantiopurity. The results of X-ray crystallographic analysis proved that Walden
      inversion occurs at the chlorinated tertiary carbon center. These results
      supported the fact that the substitution proceeds via an S(N)2 mechanism.

PMID- 22651701
TI  - Previous gestational diabetes is independently associated with increased carotid
      intima-media thickness, similarly to metabolic syndrome - a case control study.
AB  - BACKGROUND: Women with previous gestational diabetes mellitus (pGDM) face a
      higher risk of developing type 2 diabetes and, consequently, a higher
      cardiovascular risk. This study aimed to compare the carotid intima-media
      thickness (cIMT) from young women with pGDM to those with metabolic syndrome (MS)
      and to healthy controls (CG) to verify whether a past history of pGDM could be
      independently associated with increased cIMT. METHODS: This is a cross-sectional
      study performed in two academic referral centers. Seventy-nine women with pGDM,
      30 women with MS, and 60 CG aged between 18 and 47 years were enrolled. They all
      underwent physical examination and had blood glucose, total cholesterol, high
      density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDLc), and
      triglycerides determined. The cIMT was measured by ultrasound in several carotid
      segments. The primary endpoint was cIMT and clinically relevant parameters
      included as predictors were: age, systolic blood pressure, waist, BMI, total
      cholesterol, LDLc, triglycerides, fasting glucose, previous history of GDM as a
      whole group, previous history of GDM without MS, presence of DM, presence of MS,
      and parity. RESULTS: cIMT was significantly higher in pGDM when compared to CG in
      all sites of measurements (P < 0.05) except for the right common carotid. The
      pGDM women showed similar cIMT measurements to MS in all sites of measurements,
      except for the left carotid bifurcation, where it was significantly higher than
      MS (P < 0.001). In a multivariate analysis which included classical
      cardiovascular risk factors and was adjusted for confounders, pGDM was shown to
      be independently associated with increased composite cIMT (P < 0.01). The pGDM
      without risk factors further showed similar cIMT to MS (P > 0.05) and an
      increased cIMT when compared to controls (P < 0.05). CONCLUSIONS: Previous GDM
      was independently associated with increased composite cIMT in this young
      population, similarly to those with MS and regardless the presence of established
      cardiovascular risk factors.

PMID- 22651702
TI  - Electrocardiographic criteria of true left bundle branch block: a simple sign to
      predict a better clinical and instrumental response to CRT.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has proved to be very
      effective in improving morbidity and mortality in patients affected with severe
      congestive heart failure. Its efficacy has been shown to be greater in patients
      with left bundle branch block (LBBB). The aim of our study was to verify if newly
      proposed criteria for true LBBB identify patients with a better clinical and
      instrumental response to CRT. METHODS: Between May 2007 and April 2011, 111
      patients with left ventricular ejection fraction (LVEF) <= 35% and LBBB
      morphology received a CRT device and were divided into two groups according to
      QRS morphology. Group 1 (61 patients) consisted of patients with "true" LBBB
      morphology; group 2 (50 patients) consisted of patients with "false" LBBB. The
      primary endpoint was the utility of criteria for true LBBB to predict a composite
      endpoint of all-cause mortality and hospital admission with heart failure. The
      secondary endpoint was the utility of the same criteria to predict an absolute
      increase in LVEF >= 10%. RESULTS: "False" LBBB morphology and a dose of
      bisoprolol <5 mg at last follow-up were the only parameters related to clinical
      outcome in multivariate analysis (respectively: hazard ratio [HR] 3.98,
      confidence interval [CI] 95% 1.51-10.48; HR 0.15, CI 95% 0.05-0.43). "True" LBBB
      morphology was the only variable significantly related to a greater increase in
      LVEF (HR 4.57, CI 95% 1.36-8.28). CONCLUSION: True LBBB morphology is related to
      a higher event-free survival rate in CRT patients and better echocardiographic
      response.

PMID- 22651703
TI  - FDG-PET is a good biomarker of both early response and acquired resistance in
      BRAFV600 mutant melanomas treated with vemurafenib and the MEK inhibitor GDC
      0973.
AB  - BACKGROUND: The BRAF inhibitor, vemurafenib, has recently been approved for the
      treatment of metastatic melanoma in patients harboring BRAFV600 mutations.
      Currently, dual BRAF and MEK inhibition are ongoing in clinical trials with the
      goal of overcoming the acquired resistance that has unfortunately developed in
      some vemurafenib patients. FDG-PET measures of metabolic activity are
      increasingly employed as a pharmacodynamic biomarker for guiding single-agent or
      combination therapies by gauging initial drug response and monitoring disease
      progression. However, since tumors are inherently heterogeneous, investigating
      the effects of BRAF and MEK inhibition on FDG uptake in a panel of different
      melanomas could help interpret imaging outcomes. METHODS: 18 F-FDG uptake was
      measured in vitro in cells with wild-type and mutant (V600) BRAF, and in melanoma
      cells with an acquired resistance to vemurafenib. We treated the cells with
      vemurafenib alone or in combination with MEK inhibitor GDC-0973. PET imaging was
      used in mice to measure FDG uptake in A375 melanoma xenografts and in A375 R1, a
      vemurafenib-resistant derivative. Histological and biochemical studies of glucose
      transporters, the MAPK and glycolytic pathways were also undertaken. RESULTS: We
      demonstrate that vemurafenib is equally effective at reducing FDG uptake in cell
      lines harboring either heterozygous or homozygous BRAFV600 but ineffective in
      cells with acquired resistance or having WT BRAF status. However, combination
      with GDC-0973 results in a highly significant increase of efficacy and inhibition
      of FDG uptake across all twenty lines. Drug-induced changes in FDG uptake were
      associated with altered levels of membrane GLUT-1, and cell lines harboring RAS
      mutations displayed enhanced FDG uptake upon exposure to vemurafenib.
      Interestingly, we found that vemurafenib treatment in mice bearing drug-resistant
      A375 xenografts also induced increased FDG tumor uptake, accompanied by increases
      in Hif-1alpha, Sp1 and Ksr protein levels. Vemurafenib and GDC-0973 combination
      efficacy was associated with decreased levels of hexokinase II, c-RAF, Ksr and p
      MEK protein. CONCLUSIONS: We have demonstrated that 18 F-FDG-PET imaging reflects
      vemurafenib and GDC-0973 action across a wide range of metastatic melanomas. A
      delayed post-treatment increase in tumor FDG uptake should be considered
      carefully as it may well be an indication of acquired drug resistance. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01271803.

PMID- 22651704
TI  - The connector SafA interacts with the multi-sensing domain of PhoQ in Escherichia
      coli.
AB  - Sensor histidine kinases of two-component signal transduction systems (TCSs)
      respond to various environmental signals and transduce the external stimuli
      across the cell membrane to their cognate response regulators. Recently, membrane
      proteins that modulate sensory systems have been discovered. Among such proteins
      is SafA, which activates the PhoQ/PhoP TCS by direct interaction with the sensor
      PhoQ. SafA is directly induced by the EvgS/EvgA TCS, thus connecting the two
      TCSs, EvgS/EvgA and PhoQ/PhoP. We investigated how SafA interacted with PhoQ.
      Bacterial two-hybrid and reporter assays revealed that the C-terminal region (41
      65 aa) of SafA activated PhoQ at the periplasm. Adding synthetic SafA(41-65)
      peptide to the cell culture also activated PhoQ/PhoP. Furthermore, direct
      interaction between SafA(41-65) and the sensor domain of PhoQ was observed by
      means of surface plasmon resonance. NMR spectroscopy of (15) N-labelled PhoQ
      sensor domain confirmed that SafA and Mg(2+)  provoked a different conformational
      change of PhoQ. Site-directed mutagenesis studies revealed that R53, within
      SafA(41-65), was important for the activation of PhoQ, and D179 of the PhoQ
      sensor domain was required for its activation by SafA. SafA activated PhoQ by a
      different mechanism from cationic antimicrobial peptides and acidic pH, and
      independent of divalent cations and MgrB.

PMID- 22651706
TI  - The influence of seat backrest angle on perceived discomfort during exposure to
      vertical whole-body vibration.
AB  - National and International Standards (e.g. BS 6841 and ISO 2631-1) provide
      methodologies for the measurement and assessment of whole-body vibration in terms
      of comfort and health. The EU Physical Agents (Vibration) Directive (PAVD)
      provides criteria by which vibration magnitudes can be assessed. However, these
      standards only consider upright seated (90 degrees ) and recumbent (0 degrees )
      backrest angles, and do not provide guidance for semi-recumbent postures. This
      article reports an experimental programme that investigated the effects of
      backrest angle on comfort during vertical whole-body vibration. The series of
      experiments showed that a relationship exists between seat backrest angle, whole
      body vibration frequency and perceived levels of discomfort. The recumbent
      position (0 degrees ) was the most uncomfortable and the semi-recumbent positions
      of 67.5 degrees  and 45 degrees  were the least uncomfortable. A new set of
      frequency weighting curves are proposed which use the same topology as the
      existing BS and ISO standards. These curves could be applied to those exposed to
      whole-body vibration in semi-recumbent postures to augment the existing
      standardised methods. PRACTITIONER SUMMARY: Current vibration standards provide
      guidance for assessing exposures for seated, standing and recumbent positions,
      but not for semi-recumbent postures. This article reports new experimental data
      systematically investigating the effect of backrest angle on discomfort
      experienced. It demonstrates that most discomfort is caused in a recumbent
      posture and that least was caused in a semi-recumbent posture.

PMID- 22651705
TI  - Heritability of non-alcoholic fatty liver disease and association with abnormal
      vascular parameters: a twin study.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been linked to
      increased cardiovascular morbidity. However, genetic factors have an unclear role
      in this condition. AIMS: To analyse heritability of NAFLD and its association
      with abnormal vascular parameters in a large twin cohort. METHODS: Anthropometric
      and lipid metabolic parameters were obtained from 208 adult Hungarian twins (63
      monozygotic and 41 dizygotic pairs; 58 men and 150 women; age 43.7 +/- 16.7
      years). B-mode ultrasonography was performed to detect steatosis and categorize
      severity. Brachial and aortic augmentation indices and aortic pulse wave velocity
      were assessed using oscillometry (TensioMed Arteriograph). Carotid intima media
      thickness (IMT) was measured using ultrasonography on the proximal common, distal
      common and internal carotid arteries. RESULTS: NAFLD was identified in 47
      subjects (22.6%), of which 44 (93.6%) had mild and 3 (6.4%) had moderate
      steatosis. These subjects were older (age: 50.9 +/- 14.3 vs. 41.5 +/- 16.7 years,
      P < 0.001) and had a higher body mass index (BMI; 30.1 +/- 5.2 vs. 24.6 +/- 4.1
      km/m(2) , P < 0.001) than non-NAFLD twins. Based on 91 same-sex twin pairs,
      heritability analysis indicated no discernible role for genetic components in the
      presence of NAFLD (95% confidence interval, 0.0-36.0%), while shared and unshared
      environmental effects accounted for 74.2% and 25.8% of variations adjusted for
      age and BMI. Augmentation indices and carotid IMT in twins with NAFLD were
      increased at most examined locations (P < 0.05-P < 0.001). CONCLUSION: These
      findings do not support heritability of NAFLD, although it coexists with vascular
      parameters linked to increased cardiovascular risk, underscoring the importance
      and value of prevention in this very common disorder.

PMID- 22651792
TI  - Grading breast cancer on microarray samples: comparison with Nottingham grade,
      and use of boosting classification.
AB  - AIMS: Nottingham breast cancer grade (NG) is a subjective morphological
      assessment based on evaluation of the entire tumour. The value of many novel
      immunohistochemical and molecular markers is being assessed on tiny microarray
      samples of tumour and compared with NG. The aim of this study was to investigate
      whether tumour morphology in microarray samples would correlate with NG. METHODS
      AND RESULTS: We examined over 40 morphological features in each of 568 breast
      tumour samples on a microarray obtained from the US National Cancer Institute.
      Evaluations were subjective, and features were recorded as being present or
      absent in each tumour. Subsequently, on the basis of binary results, a boosting
      classification algorithm was implemented to help assign a 'microarray score' and
      'microarray grade' to each tumour. Microarray grade was significantly correlated
      with NG (P < 0.01). High-grade versus low-grade discrepancies were rare (five of
      568 samples). CONCLUSIONS: The strong correlation of microarray grade with NG
      supports pathologist reproducibility in subjective evaluations.

PMID- 22651793
TI  - In search of the big question.

PMID- 22651795
TI  - Does topical lidocaine before tracheal intubation attenuate airway responses in
      children? An observational audit.--Reply.

PMID- 22651794
TI  - Regional anesthesia: not only pain control.

PMID- 22651797
TI  - The pharmacological effects of novel 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen
      8-yl)-1H-indole-2-carboxamide derivatives on plasma lipid profile of Triton-WR
      1339-induced Wistar rats.
AB  - A novel series of 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2
      carboxamides (3c-3g) were synthesized. The present study was undertaken to
      investigate the possible antihyperlipidemic effect of these novel compounds on
      hyperlipidemic rats. Hyperlipidemia was induced by a single intraperitoneal
      injection of Triton WR-1339 (300 mg/kg). The tested animals were divided into
      normal control (NCG), hyperlipidemic control (HCG), compounds 3c-, 3d-, 3e-, 3f-,
      3g- and bezafibrate (BF)-treated groups. At a dose of 15 mg/kg, compounds 3c-3g
      and BF (100 mg/kg) significantly (p < 0.0001) reduced elevated plasma
      triglycerides levels after 12 and 24 h compared to the hyperlipidemic control
      group. However, only compounds 3e and 3g obviously showed a significant (p <
      0.0001) reduction in plasma total cholesterol levels after 12 and 24 h. Moreover,
      high-density lipoprotein cholesterol levels were significantly increased in all
      treated groups. The current study demonstrates that 5-fluoro-N-(9,10-dihydro-9,10
      dioxoanthracen-8-yl)-1H-indole-2-carboxamides (3c-3g) have a definite
      antihyperlipidemic potential and these beneficial activities may contribute to
      their cardioprotective and antiatherosclerotic role. 

PMID- 22651796
TI  - A molecular signature in blood identifies early Parkinson's disease.
AB  - BACKGROUND: The search for biomarkers in Parkinson's disease (PD) is crucial to
      identify the disease early and monitor the effectiveness of neuroprotective
      therapies. We aim to assess whether a gene signature could be detected in blood
      from early/mild PD patients that could support the diagnosis of early PD,
      focusing on genes found particularly altered in the substantia nigra of sporadic
      PD. RESULTS: The transcriptional expression of seven selected genes was examined
      in blood samples from 62 early stage PD patients and 64 healthy age-matched
      controls. Stepwise multivariate logistic regression analysis identified five
      genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds
      ratio [OR] 0.73; 95% confidence interval [CI] 0.60-0.90), huntingtin interacting
      protein-2 (OR 1.32; CI 1.08-1.61), aldehyde dehydrogenase family 1 subfamily A1
      (OR 0.86; 95% CI 0.75-0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60
      0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14-1.70). At a 0.5 cut
      off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3
      and 89.1 respectively and the area under the receiving operating curve (ROC AUC)
      was 0.96. The performance of the five-gene classifier on the de novo PD
      individuals alone composing the early PD cohort (n = 38), resulted in a similar
      ROC with an AUC of 0.95, indicating the stability of the model and also, that
      patient medication had no significant effect on the predictive probability (PP)
      of the classifier for PD risk. The predictive ability of the model was validated
      in an independent cohort of 30 patients at advanced stage of PD, classifying
      correctly all cases as PD (100% sensitivity). Notably, the nominal average value
      of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the
      early PD group (0.83 (SD = 0.22)), suggesting a potential for the model to assess
      disease severity. Lastly, the gene panel fully discriminated between PD and
      Alzheimer's disease (n = 29). CONCLUSIONS: The findings provide evidence on the
      ability of a five-gene panel to diagnose early/mild PD, with a possible
      diagnostic value for detection of asymptomatic PD before overt expression of the
      disorder.

PMID- 22651798
TI  - Synthesis and antimicrobial activity of some new hydrazone-bridged thiazole
      pyrrole derivatives.
AB  - In this work, we synthesized fourteen different compounds which contain hydrazone
      bridged thiazole and pyrrole rings. For this purpose, pyrrole-2-carboxaldehydes
      were reacted directly with thiosemicarbazide in ethanol and then obtained
      thiosemicarbazones were condensed with alpha-bromoacetophenone derivatives
      (Hantzsch reaction) to give 1-substituted pyrrole-2-carboxaldehyde [4-(4
      substituted phenyl)-1,3-thiazol-2-yl] hydrazones. The structures of the obtained
      compounds were elucidated by using IR, (1)H-NMR and FAB(+)-MS spectral data and
      elemental analyses results. All of the compounds were screened for their
      antibacterial and antifungal activities against twelve different microorganisms
      by using microbroth dilution method. Ketoconazole and chloramphenicol were used
      as standard drugs. All of the compounds showed good activity against
      Staphylococcus aureus and Enterococcus faecalis. 

PMID- 22651799
TI  - Purification and characterization of OXA-23 from Acinetobacter baumannii.
AB  - Although the existence of bla(OXA-23) is reported in various parts of the world,
      the product of bla(OXA-23) gene, OXA-23, has not been purified and its kinetic
      properties are not known. In this study, OXA-23 of Acinetobacter baumannii
      isolated from Kocaeli University intensive care unit was characterized after
      purification using recombinant methods. Preliminary results showed that
      conventional protein purification methods were not effective for purification of
      OXA-23. Therefore, OXA-23 was fused to maltose-binding protein of Escherichia
      coli, the fused protein was expressed and purified to homogeneity. Kinetic
      properties of the pure protein were then studied with substrates e.g., imipenem,
      meropenem, cefepime, ceftazidime, ampicilline, piperacillin, penicillin G, and
      nitrocefin. Also clavulanic acid, tazobactam, and sulbactam concentrations that
      inhibit 50% of OXA-23 enzyme activity were calculated. Modelling of OXA-23
      revealed its ionic surface structure, conformation in the fused form and its
      topology allowing us to make predictions for OXA-23 substrate specificity.

PMID- 22651800
TI  - New 5-(nitroheteroaryl)-1,3,4-thiadiazols containing acyclic amines at C-2:
      synthesis and SAR study for their antileishmanial activity.
AB  - A novel series of 5-(5-nitrofuran-2-yl)-and 5-(5-nitrothiophen-2-yl)-1,3,4
      thiadiazole-2-amines bearing acyclic amine at C-2 position of thiadiazole ring
      were synthesized and evaluated in vitro against promastigote and amastigote forms
      of Leishmania major. The structure-activity of series was investigated by
      studying 40 compounds. The most active derivatives were hydroxypropylamino- and
      methoxypropylamino- analogs of 5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazole
      (compounds 29 and 32, respectively) with highest selectivity index (SI >12). 

PMID- 22651801
TI  - Synthesis of a new class of antimicrobial agents incorporating the indolin-2-one
      moiety.
AB  - New furanone derivatives incorporating the indolin-2-one moiety 3 were prepared
      via the Perkin reaction of isatins 1 with aroylpropionic acids 2 under
      conventional conditions or microwave irradiation. A series of functionally
      heterocyclic derivatives (e.g., pyridazines, pyrroles, and sulfonamides)
      incorporating the indolin-2-one moiety was achieved via reaction of 3 with
      different reagents under microwave irradiation conditions. The newly synthesized
      compounds were characterized on the basis of FTIR, (1)H, (13)C NMR and mass
      spectral studies. Some of the new synthesized compounds were screened for
      antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and
      Bacillus cereus), Gram-negative bacteria (Escherichia coli and Shigilla flexneri)
      and antifungal activity against Aspergillus flavus and Candida albicans. Compound
      8 j was equipotent to chloramphenicol in inhibiting the growth of E. coli minimum
      inhibitory concentration (MIC 2.5 MUg/mL). Compound 8j may possibly be used as a
      lead compound for developing a new antibacterial agents. The antibacterial
      activity is expressed as the corresponding MIC (MUg/mL) values. 

PMID- 22651802
TI  - Diffusiophoresis of a spherical soft particle in electrolyte gradients.
AB  - An analytical study of the diffusiophoresis (consisting of electrophoresis and
      chemiphoresis) of a charged soft particle (or composite particle) composed of a
      spherical rigid core and a surrounding porous shell in an electrolyte solution
      prescribed with a uniform concentration gradient is presented. In the solvent
      permeable and ion-penetrable porous surface layer of the particle, idealized
      frictional segments with fixed charges are assumed to distribute at a constant
      density. The electrokinetic equations that govern the electric potential profile,
      ionic concentration distributions, and fluid flow field inside and outside the
      porous layer of the particle are linearized by assuming that the system is only
      slightly distorted from equilibrium. Using a regular perturbation method, these
      linearized equations are solved with the fixed charge densities on the rigid core
      surface and in the porous shell as the small perturbation parameters. An
      analytical expression for the diffusiophoretic mobility of the soft sphere in
      closed form is obtained from a balance between its electrostatic and hydrodynamic
      forces. This expression, which is correct to the second order of the fixed charge
      densities, is valid for arbitrary values of kappaa, lambdaa, and r(0)/a, where
      kappa is the reciprocal of the Debye screening length, lambda is the reciprocal
      of the length characterizing the extent of flow penetration inside the porous
      layer, a is the radius of the soft sphere, and r(0) is the radius of the rigid
      core of the particle. It is shown that a soft particle bearing no net charge can
      undergo diffusiophoresis (electrophoresis and chemiphoresis), and the direction
      of its diffusiophoretic velocity is decided by the fixed charges in the porous
      surface layer of the particle. In the limiting cases of large and small values of
      r(0)/a, the analytical solution describing the diffusiophoretic mobility for a
      charged soft sphere reduces to that for a charged rigid sphere and for a charged
      porous sphere, respectively.

PMID- 22651803
TI  - On crystal versus fiber formation in dipeptide hydrogelator systems.
AB  - Naphthalene dipeptides have been shown to be useful low-molecular-weight
      gelators. Here we have used a library to explore the relationship between the
      dipeptide sequence and the hydrogelation efficiency. A number of the naphthalene
      dipeptides are crystallizable from water, enabling us to investigate the
      comparison between the gel/fiber phase and the crystal phase. We succeeded in
      crystallizing one example directly from the gel phase. Using X-ray
      crystallography, molecular modeling, and X-ray fiber diffraction, we show that
      the molecular packing of this crystal structure differs from the structure of the
      gel/fiber phase. Although the crystal structures may provide important insights
      into stabilizing interactions, our analysis indicates a rearrangement of
      structural packing within the fibers. These observations are consistent with the
      fibrillar interactions and interatomic separations promoting 1D assembly whereas
      in the crystals the peptides are aligned along multiple axes, allowing 3D growth.
      This observation has an impact on the use of crystal structures to determine
      supramolecular synthons for gelators.

PMID- 22651804
TI  - Efficiency of genomic selection using Bayesian multi-marker models for traits
      selected to reflect a wide range of heritabilities and frequencies of detected
      quantitative traits loci in mice.
AB  - BACKGROUND: Genomic selection uses dense single nucleotide polymorphisms (SNP)
      markers to predict breeding values, as compared to conventional evaluations which
      estimate polygenic effects based on phenotypic records and pedigree information.
      The objective of this study was to compare polygenic, genomic and combined
      polygenic-genomic models, including mixture models (labelled according to the
      percentage of genotyped SNP markers considered to have a substantial effect,
      ranging from 2.5% to 100%). The data consisted of phenotypes and SNP genotypes
      (10,946 SNPs) of 2,188 mice. Various growth, behavioural and physiological traits
      were selected for the analysis to reflect a wide range of heritabilities (0.10 to
      0.74) and numbers of detected quantitative traits loci (QTL) (1 to 20) affecting
      those traits. The analysis included estimation of variance components and cross
      validation within and between families. RESULTS: Genomic selection showed a high
      predictive ability (PA) in comparison to traditional polygenic selection,
      especially for traits of moderate heritability and when cross-validation was
      between families. This occurred although the proportion of genomic variance of
      traits using genomic models was 22 to 33% smaller than using polygenic models.
      Using a 2.5% mixture genomic model, the proportion of genomic variance was 79%
      smaller relative to the polygenic model. Although the proportion of variance
      explained by the markers was reduced further when a smaller number of SNPs was
      assumed to have a substantial effect on the trait, PA of genomic selection for
      most traits was little affected. These low mixture percentages resulted in
      improved estimates of single SNP effects. Genomic models implemented for traits
      with fewer QTLs showed even lower PA than the polygenic models. CONCLUSIONS:
      Genomic selection generally performed better than traditional polygenic
      selection, especially in the context of between family cross-validation. Reducing
      the number of markers considered to affect the trait did not significantly change
      PA for most traits, particularly in the case of within family cross-validation,
      but increased the number of markers found to be associated with QTLs. The
      underlying number of QTLs affecting the trait has an effect on PA, with a smaller
      number of QTLs resulting in lower PA using the genomic model compared to the
      polygenic model.

PMID- 22651805
TI  - The relationship between hand osteoarthritis and serum leptin concentration in
      participants of the Third National Health and Nutrition Examination Survey.
AB  - INTRODUCTION: Leptin has been suspected to contribute to the development of
      osteoarthritis (OA). However, this hypothesis has not been tested in large-scale
      hand OA cohorts. Our study aimed to determine whether there is a cross-sectional
      relationship between serum leptin levels and hand OA in a population-based sample
      of US adults. METHOD: We used the Third National Health and Nutrition Examination
      Survey (NHANES III), a national cross-sectional population-based survey, to study
      the relationship between hand OA and serum leptin concentration. We applied
      previously established classification criteria for hand OA. Patients with
      rheumatoid arthritis were excluded. Potential confounders included sex, body mass
      index, the presence of polyarticular OA, diabetes, and total cholesterol. We
      estimated unadjusted mean leptin concentration by hand OA status and by all
      confounders. We further developed a linear regression model to assess mean leptin
      levels, adjusted for appropriate confounders. RESULTS: Of 2,477 subjects in the
      NHANES III sample that had a hand examination and did not have rheumatoid
      arthritis, 1,056 (42.6%) had a leptin measurement and were included in the
      analysis. Subjects with and without leptin measurement had similar demographic
      characteristics. We did not find any significant differences in mean serum leptin
      levels in subjects with symptomatic hand OA (7.38 ng/ml in males (95% confidence
      interval (CI) = 5.31, 9.46) and 21.55 ng/ml in females (95% CI = 17.08, 26.02)),
      asymptomatic hand OA (6.69 ng/ml in males (95% CI = 5.19, 8.18) and 17.09 ng/ml
      in females (95% CI = 15.00, 19.18)), and no hand OA (8.22 ng/ml in males (95% CI
      = 7.47, 8.97) and 20.77 ng/ml in females (95% CI = 18.01, 23.53)) in the
      unadjusted analysis. In a multivariable linear regression model that included
      variables of hand OA status, age, race/ethnicity, and obesity status, we found no
      statistically significant association between serum leptin and hand OA status.
      CONCLUSIONS: In this cross-sectional study of a large representative US cohort,
      we did not find any evidence to support the hypothesis that serum leptin is
      associated with hand OA.

PMID- 22651806
TI  - Ketone formation via mild nickel-catalyzed reductive coupling of alkyl halides
      with aryl acid chlorides.
AB  - The present work highlights unprecedented Ni-catalyzed reductive coupling of
      unactivated alkyl iodides with aryl acid chlorides to efficiently generate alkyl
      aryl ketones under mild conditions.

PMID- 22651807
TI  - Traumatic brain injury and subsequent risk of developing brain tumors.

PMID- 22651808
TI  - A comparative review of cell culture systems for the study of microglial biology
      in Alzheimer's disease.
AB  - Over the past two decades, it has become increasingly apparent that Alzheimer's
      disease neuropathology is characterized by activated microglia (brain resident
      macrophages) as well as the classic features of amyloid plaques and
      neurofibrillary tangles. The intricacy of microglial biology has also become
      apparent, leading to a heightened research interest in this particular cell type.
      Over the years a number of different microglial cell culturing techniques have
      been developed to study either primary mammalian microglia, or immortalized cell
      lines. Each microglial system has advantages and disadvantages and should be
      selected for its appropriateness in a particular research context. This review
      summarizes several of the most common microglial cell culture systems currently
      being employed in Alzheimer's research including primary microglia; BV2 and N9
      retroviral immortalized microglia; human immortalized microglia (HMO6); and
      spontaneously immortalized rodent microglial lines (EOC lines and HAPI cells).
      Particularities of cell culture requirements and characteristics of microglial
      behavior, especially in response to applied inflammogen stimuli, are compared and
      discussed across these cell types.

PMID- 22651809
TI  - Spatial pattern of P waves in paroxysmal atrial fibrillation patients in sinus
      rhythm and controls.
AB  - BACKGROUND: Measuring body surface potentials in the assessment of the electrical
      activity of the heart is the most commonly used noninvasive method for diagnosing
      cardiac arrhythmias. Paroxysmal atrial fibrillation (PAF) patients have disturbed
      cardiac electrophysiology but the detailed characteristics of atrial activation
      on the body surface are unknown. METHODS: P waves from 60 sites on the body
      surface were analyzed from 10 PAF patients in sinus rhythm (PAF group) and 10
      healthy controls (HC group). Evolution of atrial depolarization was described
      qualitatively by maps of P-wave amplitudes. P-wave dipole evolution was described
      quantitatively by measuring the changing location (body site) and amplitude of
      the dipole positive and negative pole peaks. RESULTS: Both groups exhibited
      similar dipolar structure with an area of positive and an area of negative
      potentials. Over the depolarization cycle, there were significant changes in the
      location of the dipole with the positive pole rotating anteriorly right to left
      by two electrode sites (10 cm) (P = 0.001). There were significant differences
      between groups with the positive pole in PAF offset to the right of the chest by
      0.43 (0.38) strips compared to HC (P < 0.007). Compared to controls, the PAF
      group positive poles reached peak amplitude sooner (49 [11] ms vs 65 [14] ms, P =
      0.012) and negative poles reached peak amplitude later (74 [13] ms vs 62 [8] ms,
      P = 0.019). CONCLUSION: Atrial depolarization is characterized by a single dipole
      with time-varying amplitude and orientation with significant differences in
      dipole trajectory between patients with PAF and HCs.

PMID- 22651810
TI  - Validation of the Japanese version of the EORTC hepatocellular carcinoma-specific
      quality of life questionnaire module (QLQ-HCC18).
AB  - BACKGROUND: This Study Examined The Measurement Properties Of The Japanese
      Version Of The European Organisation for Research and Treatment of Cancer (EORTC)
      Hepatocellular Carcinoma-Specific Quality of Life Questionnaire (QLQ-HCC18).
      METHODS: EORTC quality of life (QOL) translation guidelines were followed to
      create a Japanese version of the EORTC QLQ-HCC18. This was then administered to
      192 patients with hepatocellular carcinoma along with the EORTC QLQ-C30 and FACT
      Hep questionnaires. Tests for reliability and validity were conducted including
      comparison of scores between the EORTC and FACT questionnaire and detailed
      assessment of the new scales and items in clinically distinct groups of patients.
      RESULTS: Multi-trait scaling analysis confirmed three putative scales in the QLQ
      HCC18, fatigue, fever and nutrition. Cronbach's alpha for these scales were
      between 0.68 and 0.78. The QLQ-HCC18 scales correlated with scales measuring
      similar items in the FACT-Hep and the questionnaire was stable over time with an
      intra-class correlation score of 0.70 for almost all scales. The questionnaire
      had the ability to distinguish between patients with different Karnofsky
      Performance Status, and Child-Pugh liver function class. CONCLUSIONS: The
      Japanese version of EORTC QLQ-HCC18 is a reliable supplementary measure to use
      with EORTC QLQ-C30 to measure QOL in Japanese patients with hepatocellular
      carcinoma.

PMID- 22651811
TI  - VERSE: a varying effect regression for splicing elements discovery.
AB  - Identification of splicing regulatory elements (SREs) deserves special attention
      because these cis-acting short sequences are vital parts of splicing code. The
      fact that a variety of other biological signals cooperatively govern the splicing
      pattern indicates the necessity of developing novel tools to incorporate
      information from multiple sources to improve splicing factor binding sites
      prediction. Under this context, we proposed a Varying Effect Regression for
      Splicing Elements (VERSE) to discover intronic SREs in the proximity of exon
      junctions by integrating other biological features. As a result, 1562 intronic
      SREs were identified in 16 human tissues, many of which overlapped with
      experimentally verified binding motifs for several well-known splicing factors,
      including FOX-1, PTB, hnRNP A/B, hnRNP F/H, and so on. The discovered tissue,
      region, and conservation preferences of the putative motifs demonstrate that
      splice site selection is a complicated process that needs subtle and delicate
      regulation. VERSE may serve as a powerful tool to not only discover SREs by
      incorporating additional informative signals but also precisely quantify their
      varying contribution under different biological contexts.

PMID- 22651812
TI  - A novel genome-information content-based statistic for genome-wide association
      analysis designed for next-generation sequencing data.
AB  - The genome-wide association studies (GWAS) designed for next-generation
      sequencing data involve testing association of genomic variants, including
      common, low frequency, and rare variants. The current strategies for association
      studies are well developed for identifying association of common variants with
      the common diseases, but may be ill-suited when large amounts of allelic
      heterogeneity are present in sequence data. Recently, group tests that analyze
      their collective frequency differences between cases and controls shift the
      current variant-by-variant analysis paradigm for GWAS of common variants to the
      collective test of multiple variants in the association analysis of rare
      variants. However, group tests ignore differences in genetic effects among SNPs
      at different genomic locations. As an alternative to group tests, we developed a
      novel genome-information content-based statistics for testing association of the
      entire allele frequency spectrum of genomic variation with the diseases. To
      evaluate the performance of the proposed statistics, we use large-scale
      simulations based on whole genome low coverage pilot data in the 1000 Genomes
      Project to calculate the type 1 error rates and power of seven alternative
      statistics: a genome-information content-based statistic, the generalized T(2),
      collapsing method, multivariate and collapsing (CMC) method, individual chi(2)
      test, weighted-sum statistic, and variable threshold statistic. Finally, we apply
      the seven statistics to published resequencing dataset from ANGPTL3, ANGPTL4,
      ANGPTL5, and ANGPTL6 genes in the Dallas Heart Study. We report that the genome
      information content-based statistic has significantly improved type 1 error rates
      and higher power than the other six statistics in both simulated and empirical
      datasets.

PMID- 22651813
TI  - In this special issue of the Journal of Computational Biology, we take great
      pleasure in celebrating the landmark birthdays of two leaders in our field.

PMID- 22651814
TI  - A revised intracarotid etomidate memory (Wada) procedure.
AB  - OBJECTIVES: To evaluate unilateral memory function by the means of a modified
      Montreal etomidate speech and memory procedure (e-SAM) in epilepsy patients who
      were candidates for standard anterior temporal lobectomy involving resection of
      mesial temporal lobe structures. MATERIALS AND METHODS: After the first three
      patients experienced significant side effects with the e-SAM procedure, we
      modified the procedure to a single bolus injection. The neuropsychological data
      of all 21 patients who underwent unilateral memory testing by means of
      intracarotid injection of etomidate were analyzed. RESULTS: There was a
      significant difference in memory scores when injections were on the side
      ipsilateral to the epileptogenic focus compared with when the injections were on
      the contralateral side (P < 0.01), supposedly reflecting unilateral hippocampal
      memory function and dysfunction. In addition, the procedural modification
      resulted in eradication of all major side effects in the ensuing 18 patients.
      CONCLUSIONS: The technical modification of the Montreal procedure from continuous
      to bolus injection effectively enabled the demonstration of the relative weakness
      of the memory function of the epileptogenic hemisphere. The revised etomidate
      procedure provided the clinical information on unilateral hippocampal memory
      function necessary for surgical decision.

PMID- 22651815
TI  - Effect of orientation of the peptide-bridge dipole moment on the properties of
      fullerene-peptide-radical systems.
AB  - We synthesized two series of compounds in which a nitroxide radical and a
      fullerene C(60) moiety were kept separated by a 3(10)-helical peptide bridge
      containing two intramolecular C?O...H-N hydrogen bonds. The direction of the
      resulting molecular dipole moment could be reversed by switching the position of
      fullerene and nitroxide with respect to the peptide nitrogen and carbon termini.
      The resulting fullerene-peptide-radical systems were compared to the behaviors of
      otherwise identical peptides but lacking either C(60) or the free radical moiety.
      Electrochemical analysis and chemical nitroxide reduction experiments show that
      the dipole moment of the helix significantly affects the redox properties of both
      electroactive groups. Besides providing evidence of a folded helical conformation
      for the peptide bridge, IR and NMR results highlight a strong effect of peptide
      orientation on the spectral patterns, pointing to a specific interaction of one
      of the helical orientations with the C(60) moiety. Time-resolved EPR spectra show
      not only that for both systems triplet quenching by nitroxide induces spin
      polarization of the radical spin sublevels, but also that the coupling
      interaction can be either weak or strong depending on the orientation of the
      peptide dipole. As opposed to the concept of dyads, the molecules investigated
      are thus better described as fullerene-peptide-radical systems to stress the
      active role of the bridge as an important ingredient capable of tuning the
      system's physicochemical properties.

PMID- 22651817
TI  - CD34+ megakaryocytes (>=30%) are associated with megaloblastic anaemia and non
      acute myeloid neoplasia.
AB  - AIMS: To evaluate the sensitivity and specificity of CD34 staining of
      megakaryocytes (MKs), in order to distinguish non-neoplastic and neoplastic bone
      marrows (BMs). METHODS AND RESULTS: Three hundred BMs (120 non-neoplastic and 180
      neoplastic) were evaluated for percentage and intensity of CD34 staining of MKs.
      The selected non-neoplastic cases included anaemia, autoimmune conditions, immune
      thrombocytopenia (ITP), and staging BMs. The neoplastic cases included
      myelodysplastic syndromes and/or myeloproliferative neoplasms (MDS, MPN,
      MDS/MPN). Eight per cent of non-neoplastic (9/120) cases and 13% of neoplastic
      (24/180) cases showed >=30% CD34+ MKs, and these were essentially restricted to
      cases of megaloblastic anaemia (MBA) and non-acute myeloid neoplasms. The finding
      of >=30% CD34+ MKs did not distinguish between categories of non-acute myeloid
      neoplasms. MDS cases with >=30% CD34+ MKs had lower platelet counts than cases
      with <30% (P = 0.03). CONCLUSION: In complex BM cases, the presence of >=30%
      CD34+ MKs constitutes a potentially useful diagnostic tool with which to
      distinguish non-acute myeloid neoplasms and MBA from non-MBA reactive conditions,
      for minimal additional cost.

PMID- 22651818
TI  - Endogenous steroid profiling by gas chromatography-tandem mass spectrometry and
      multivariate statistics for the detection of natural hormone abuse in cattle.
AB  - For years it has been suspected that natural hormones are illegally used as
      growth promoters in cattle in the European Union. Unfortunately there is a lack
      of methods and criteria that can be used to detect the abuse of natural hormones
      and distinguish treated from non-treated animals. Pattern recognition of steroid
      profiles is a promising approach for tracing/detecting the abuse of natural
      hormones administered to cattle. Traditionally steroids are analysed in urine as
      free steroid after deconjugation of the glucuronide (and sulphate) conjugates.
      The disadvantage of this deconjugation is that valuable information about the
      steroid profile in the sample is lost. In this study we develop a method to
      analyse steroids at very low concentration levels (ng l(-1)) for the free
      steroid, glucuronide and sulphate conjugates in urine samples. This method was
      used to determine concentrations of natural (pro)hormones in a large population
      (n = 620) of samples from male and female bovine animals and from bovine animals
      treated with testosterone-cypionate, estradiol-benzoate, dihydroepiandrosterone
      and pregnenolone. The data acquired were used to build a statistical model
      applying the multivariate technique 'Soft Independent Modeling of Class Analogy'
      (SIMCA). It is demonstrated that by using this model the results of the urine
      analysis can indicate which animal may have had illegal treatment with natural
      (pro)hormones.

PMID- 22651816
TI  - Conservation of thiol-oxidative stress responses regulated by SigR orthologues in
      actinomycetes.
AB  - Numerous thiol-reactive compounds cause oxidative stress where cells counteract
      by activation of survival strategies regulated by thiol-based sensors. In
      Streptomyces coelicolor, a model actinomycete, a sigma/antisigma pair SigR/RsrA
      controls the response to thiol-oxidative stress. To unravel its full
      physiological functions, chromatin immuno-precipitation combined with sequence
      and transcript analyses were employed to identify 108 SigR target genes in S.
      coelicolor and to predict orthologous regulons across actinomycetes. In addition
      to reported genes for thiol homeostasis, protein degradation and ribosome
      modulation, 64 additional operons were identified suggesting new functions of
      this global regulator. We demonstrate that SigR maintains the level and activity
      of the housekeeping sigma factor HrdB during thiol-oxidative stress, a novel
      strategy for stress responses. We also found that SigR defends cells against UV
      and thiol-reactive damages, in which repair UvrA takes a part. Using a refined
      SigR-binding sequence model, SigR orthologues and their targets were predicted in
      42 actinomycetes. This revealed a conserved core set of SigR targets to function
      for thiol homeostasis, protein quality control, possible modulation of
      transcription and translation, flavin-mediated redox reactions, and Fe-S
      delivery. The composition of the SigR regulon reveals a robust conserved
      physiological mechanism to deal with thiol-oxidative stress from bacteria to
      human.

PMID- 22651819
TI  - Lead concentration in meat from lead-killed moose and predicted human exposure
      using Monte Carlo simulation.
AB  - Lead-based hunting ammunitions are still common in most countries. On impact such
      ammunition releases fragments which are widely distributed within the carcass. In
      Norway, wild game is an important meat source for segments of the population and
      95% of hunters use lead-based bullets. In this paper, we have investigated the
      lead content of ground meat from moose (Alces alces) intended for human
      consumption in Norway, and have predicted human exposure through this source.
      Fifty-two samples from different batches of ground meat from moose killed with
      lead-based bullets were randomly collected. The lead content was measured by
      atomic absorption spectroscopy. The lead intake from exposure to moose meat over
      time, depending on the frequency of intake and portion size, was predicted using
      Monte Carlo simulation. In 81% of the batches, lead levels were above the limit
      of quantification of 0.03 mg kg(-1), ranging up to 110 mg kg(-1). The mean lead
      concentration was 5.6 mg kg(-1), i.e. 56 times the European Commission limit for
      lead in meat. For consumers eating a moderate meat serving (2 g kg(-1) bw), a
      single serving would give a lead intake of 11 ug kg(-1) bw on average, with
      maximum of 220 ug kg(-1) bw. Using Monte Carlo simulation, the median (and 97.5th
      percentile) predicted weekly intake of lead from moose meat was 12 ug kg(-1) bw
      (27 ug kg(-1) bw) for one serving per week and 25 ug kg(-1) bw (45 ug kg(-1) bw)
      for two servings per week. The results indicate that the intake of meat from big
      game shot with lead-based bullets imposes a significant contribution to the total
      human lead exposure. The provisional tolerable weekly intake set by the World
      Health Organization (WHO) of 25 ug kg(-1) bw is likely to be exceeded in people
      eating moose meat on a regular basis. The European Food Safety Authority (EFSA)
      has recently concluded that adverse effects may be present at even lower exposure
      doses. Hence, even occasional consumption of big game meat with lead levels as
      those found in the present study may imply an increased risk for adverse health
      effects. Children and women of child-bearing age are of special concern due to
      the neurodevelopmental effects of lead.

PMID- 22651820
TI  - Quantitative estimation of sampling uncertainties for mycotoxins in cereal
      shipments.
AB  - Many countries receive shipments of bulk cereals from primary producers. There is
      a volume of work that is on-going that seeks to arrive at appropriate standards
      for the quality of the shipments and the means to assess the shipments as they
      are out-loaded. Of concern are mycotoxin and heavy metal levels, pesticide and
      herbicide residue levels, and contamination by genetically modified organisms
      (GMOs). As the ability to quantify these contaminants improves through improved
      analytical techniques, the sampling methodologies applied to the shipments must
      also keep pace to ensure that the uncertainties attached to the sampling
      procedures do not overwhelm the analytical uncertainties. There is a need to
      understand and quantify sampling uncertainties under varying conditions of
      contamination. The analysis required is statistical and is challenging as the
      nature of the distribution of contaminants within a shipment is not well
      understood; very limited data exist. Limited work has been undertaken to quantify
      the variability of the contaminant concentrations in the flow of grain coming
      from a ship and the impact that this has on the variance of sampling. Relatively
      recent work by Paoletti et al. in 2006 [Paoletti C, Heissenberger A, Mazzara M,
      Larcher S, Grazioli E, Corbisier P, Hess N, Berben G, Lubeck PS, De Loose M, et
      al. 2006. Kernel lot distribution assessment (KeLDA): a study on the distribution
      of GMO in large soybean shipments. Eur Food Res Tech. 224:129-139] provides some
      insight into the variation in GMO concentrations in soybeans on cargo out-turn.
      Paoletti et al. analysed the data using correlogram analysis with the objective
      of quantifying the sampling uncertainty (variance) that attaches to the final
      cargo analysis, but this is only one possible means of quantifying sampling
      uncertainty. It is possible that in many cases the levels of contamination
      passing the sampler on out-loading are essentially random, negating the value of
      variographic quantitation of the sampling variance. GMOs and mycotoxins appear to
      have a highly heterogeneous distribution in a cargo depending on how the ship was
      loaded (the grain may have come from more than one terminal and set of storage
      silos) and mycotoxin growth may have occurred in transit. This paper examines a
      statistical model based on random contamination that can be used to calculate the
      sampling uncertainty arising from primary sampling of a cargo; it deals with what
      is thought to be a worst-case scenario. The determination of the sampling
      variance is treated both analytically and by Monte Carlo simulation. The latter
      approach provides the entire sampling distribution and not just the sampling
      variance. The sampling procedure is based on rules provided by the Canadian Grain
      Commission (CGC) and the levels of contamination considered are those relating to
      allowable levels of ochratoxin A (OTA) in wheat. The results of the calculations
      indicate that at a loading rate of 1000 tonnes h(-1), primary sample increment
      masses of 10.6 kg, a 2000-tonne lot and a primary composite sample mass of 1900
      kg, the relative standard deviation (RSD) is about 1.05 (105%) and the
      distribution of the mycotoxin (MT) level in the primary composite samples is
      highly skewed. This result applies to a mean MT level of 2 ng g(-1). The rate of
      false-negative results under these conditions is estimated to be 16.2%. The
      corresponding contamination is based on initial average concentrations of MT of
      4000 ng g(-1) within average spherical volumes of 0.3 m diameter, which are then
      diluted by a factor of 2 each time they pass through a handling stage; four
      stages of handling are assumed. The Monte Carlo calculations allow for variation
      in the initial volume of the MT-bearing grain, the average concentration and the
      dilution factor. The Monte Carlo studies seek to show the effect of variation in
      the sampling frequency while maintaining a primary composite sample mass of 1900
      kg. The overall results are presented in terms of operational characteristic
      curves that relate only to the sampling uncertainties in the primary sampling of
      the grain. It is concluded that cross-stream sampling is intrinsically unsuited
      to sampling for mycotoxins and that better sampling methods and equipment are
      needed to control sampling uncertainties. At the same time, it is shown that some
      combination of cross-cutting sampling conditions may, for a given shipment mass
      and MT content, yield acceptable sampling performance.

PMID- 22651821
TI  - Coexpression of human somatostatin receptor-2 (SSTR2) and SSTR3 modulates
      antiproliferative signaling and apoptosis.
AB  - BACKGROUND: Somatostatin (SST) via five Gi coupled receptors namely SSTR1-5 is
      known to inhibit cell proliferation by cytostatic and cytotoxic mechanisms.
      Heterodimerization plays a crucial role in modulating the signal transduction
      pathways of SSTR subtypes. In the present study, we investigated human
      SSTR2/SSTR3 heterodimerization, internalization, MAPK signaling, cell
      proliferation and apoptosis in HEK-293 cells in response to SST and specific
      agonists for SSTR2 and SSTR3. RESULTS: Although in basal conditions, SSTR2 and
      SSTR3 colocalize at the plasma membrane and exhibit heterodimerization, the cell
      surface distribution of both receptors decreased upon agonist activation and was
      accompanied by a parallel increase in intracellular colocalization. Receptors
      activation by SST and specific agonists significantly decreased cAMP levels in
      cotransfected cells in comparison to control. Agonist-mediated modulation of
      pERK1/2 was time and concentration-dependent, and pronounced in serum-deprived
      conditions. pERK1/2 was inhibited in response to SST; conversely receptor
      specific agonist treatment caused inhibition at lower concentration and
      activation at higher concentration. Strikingly, ERK1/2 phosphorylation was
      sustained upon prolonged treatment with SST but not with receptor-specific
      agonists. On the other hand, SST and receptor-specific agonists modulated p38
      phosphorylation time-dependently. The receptor activation in cotransfected cells
      exhibits Gi-dependent inhibition of cell proliferation attributed to increased
      PARP-1 expression and TUNEL staining, whereas induction of p21 and p27Kip1
      suggests a cytostatic effect. CONCLUSION: Our study provides new insights in
      SSTR2/SSTR3 mediated signaling which might help in better understanding of the
      molecular interactions involving SSTRs in tumor biology.

PMID- 22651822
TI  - Risk factors for and clinical implications of mixed Candida/bacterial bloodstream
      infections.
AB  - Mixed Candida/bacterial bloodstream infections (BSIs) have been reported to occur
      in more than 23% of all episodes of candidaemia. However, the clinical
      implications of mixed Candida/bacterial BSIs are not well known. We performed a
      retrospective case-control study of all consecutive patients with candidaemia
      over a 5-year period to determine the risk factors for and clinical outcomes of
      mixed Candida/bacterial BSIs (cases) compared with monomicrobial candidaemia
      (controls). Thirty-seven (29%) out of 126 patients with candidaemia met the
      criteria for cases. Coagulase-negative staphylococci were the predominant
      bacteria (23%) in cases. In multivariate analysis, duration of previous hospital
      stay >=7 weeks (odds ratio (OR), 2.86; 95% confidence interval (CI), 1.09-7.53),
      prior antibiotic therapy >=7 days (OR, 0.33; 95% CI, 0.14-0.82) and septic shock
      at the time of candidaemia (OR, 2.60; 95% CI, 1.14-5.93) were significantly
      associated with cases. Documented clearance of candidaemia within 3 days after
      initiation of antifungal therapy was less frequent in cases (63% vs. 84%; p =
      0.035). The difference in the rate of treatment failure at 2 weeks was not
      significant between cases (68%) and controls (62%; p = 0.55). The crude mortality
      at 6 weeks and survival through 100 days did not differ between the two patient
      groups (p = 0.56 and p = 0.80, respectively). Mixed Candida/bacterial BSIs showed
      a lower clearance rate of candidaemia during the early period of antifungal
      therapy, although the treatment response and survival rate were similar
      regardless of concurrent bacteraemia. Further studies on the clinical relevance
      of species-specific Candida-bacterial interactions are needed.

PMID- 22651823
TI  - Diazine indole acetic acids as potent, selective, and orally bioavailable
      antagonists of chemoattractant receptor homologous molecule expressed on Th2
      cells (CRTH2) for the treatment of allergic inflammatory diseases.
AB  - New classes of CRTH2 antagonists, the pyridazine linker containing indole acetic
      acids, are described. The initial hit 1 had good potency but poor permeability,
      metabolic stability, and PK. Initial optimization led to compounds of type 2 with
      low oxidative metabolism but poor oral bioavailability. Poor permeability was
      identified as a liability for these compounds. Addition of a linker between the
      indole and diazine moieties afforded a series with good potency, low rates of
      metabolism, moderate permeability, and good oral bioavailability in rodents. 32
      was identified as the development track candidate. It was potent in cell based,
      binding, and whole blood assays and exhibited good PK profile. It was efficacious
      in mouse models of contact hypersensitivity (1 mg/kg b.i.d.) and house dust (20
      mg/kg q.d.) when dosed orally. In sheep asthma, administration at 1 mg/kg iv
      completely blocked the LAR and AHR and attenuated the EAR phase.

PMID- 22651824
TI  - Mesoderm-derived stem cells: the link between the transcriptome and their
      differentiation potential.
AB  - Human adult stem cells (hASCs) have become an attractive source for autologous
      cell transplantation, tissue engineering, developmental biology, and the
      generation of human-based alternative in vitro models. Among the 3 germ cell
      layers, the mesoderm is the origin of today's most widely used and characterized
      hASC populations. A variety of isolated nonhematopoietic mesoderm-derived stem
      cell populations exist, and all of them show important differences in terms of
      function, efficacy, and differentiation potential both in vivo and in vitro. To
      better understand whether the intrinsic properties of these cells contribute to
      the overall differentiation potential of hASCs, we compared the global gene
      expression profiles of 4 mesoderm-derived stem cell populations: human adipose
      tissue-derived stromal cells, human bone marrow-derived stromal cells (hBMSCs),
      human (fore)skin-derived precursor cells (hSKPs), and human Wharton's jelly
      derived mesenchymal stem cells (hWJs). Significant differences in gene expression
      profiles were detected between distinct stem cell types. hSKPs predominantly
      expressed genes involved in neurogenesis, skin, and bone development, whereas
      hWJs and, to some extent, hBMSCs showed an increased expression of genes involved
      in cardiovascular and liver development. Interestingly, the observed differential
      gene expression of distinct hASCs could be linked to existing differentiation
      data in which hASCs were differentiated toward specific cell types. As such, our
      data suggest that the intrinsic gene expression of the undifferentiated stem
      cells has an important impact on their overall differentiation potential as well
      as their application in stem cell-based research. Yet, the factors that define
      these intrinsic properties remain to be determined.

PMID- 22651825
TI  - Molecular dynamics simulation of phosphoric acid doped monomer of
      polybenzimidazole: a potential component polymer electrolyte membrane of fuel
      cell.
AB  - Phosphoric acid doped polybenzimidazole is promising electrolyte membranes for
      high temperature (100  degrees C and above) fuel cells. Proton conduction is
      governed by the amount of phosphoric acid content in the polymer membrane. In
      this present work, we perform molecular dynamics simulations on phosphoric acid
      doped 2-phenyl-1H,1'H-5,5'-bibenzo[d]imidazole (monomer unit of
      polybenzimidazole) to characterize the structural and dynamical properties at
      varying phosphoric acid content and temperature. From the structural analysis, we
      have predicted the arrangement of the phosphoric acids, formation of H-bonds in
      the system, and the contribution of different atoms toward H-bonding. We have
      also examined the stacking of 2-phenyl-1H,1'H-5,5'-bibenzo[d]imidazole molecules
      and how their arrangement changes with the increasing amount of PA in the system
      with the help of cluster analysis. From the molecular dynamics simulation
      conducted at different temperatures and phosphoric acid doping level, we have
      predicted the diffusion of phosphoric acid and monomer. As a dynamic quantity, we
      have also calculated ring flipping of the imidazole ring of the monomer.

PMID- 22651827
TI  - Optical coherence tomography: an arrow in our quiver.

PMID- 22651828
TI  - Clinical applications of intravascular ultrasound in the implantation of drug
      eluting stents.

PMID- 22651829
TI  - Can transcranial ultrasound and microbubble therapy ever enter the mainstream in
      acute stroke therapy?

PMID- 22651826
TI  - Transcripts with in silico predicted RNA structure are enriched everywhere in the
      mouse brain.
AB  - BACKGROUND: Post-transcriptional control of gene expression is mostly conducted
      by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration
      with specific binding proteins and RNAs. In several well characterized cases,
      these RNA elements are known to form stable secondary structures. RNA secondary
      structures also may have major functional implications for long noncoding RNAs
      (lncRNAs). Recent transcriptional data has indicated the importance of lncRNAs in
      brain development and function. However, no methodical efforts to investigate
      this have been undertaken. Here, we aim to systematically analyze the potential
      for RNA structure in brain-expressed transcripts. RESULTS: By comprehensive
      spatial expression analysis of the adult mouse in situ hybridization data of the
      Allen Mouse Brain Atlas, we show that transcripts (coding as well as non-coding)
      associated with in silico predicted structured probes are highly and
      significantly enriched in almost all analyzed brain regions. Functional
      implications of these RNA structures and their role in the brain are discussed in
      detail along with specific examples. We observe that mRNAs with a structure
      prediction in their UTRs are enriched for binding, transport and localization
      gene ontology categories. In addition, after manual examination we observe
      agreement between RNA binding protein interaction sites near the 3' UTR
      structures and correlated expression patterns. CONCLUSIONS: Our results show a
      potential use for RNA structures in expressed coding as well as noncoding
      transcripts in the adult mouse brain, and describe the role of structured RNAs in
      the context of intracellular signaling pathways and regulatory networks. Based on
      this data we hypothesize that RNA structure is widely involved in transcriptional
      and translational regulatory mechanisms in the brain and ultimately plays a role
      in brain function.

PMID- 22651831
TI  - The ASCEND-HF trial: an acute study of clinical effectiveness of nesiritide and
      decompensated heart failure.
AB  - Nesiritide has been approved by the US FDA for the treatment of acute
      decompensated heart failure since 2001. Subsequently, two meta-analyses
      questioned its impact on mortality and association with worsening renal function.
      Therefore, the Acute Study of Clinical Effectiveness of Nesiritide in
      Decompensated Heart Failure trial was designed to assess the safety and efficacy
      of nesiritide in acute decompensated heart failure based on clinically relevant
      outcomes. In this article, the important findings and lessons learned from this
      landmark study are reviewed and potential evolving roles for nesiritide and
      natriuretic peptides in the future of heart failure therapy are proposed.

PMID- 22651832
TI  - Pravastatin and fenofibrate in combination (Pravafenix((r))) for the treatment of
      high-risk patients with mixed hyperlipidemia.
AB  - Pravafenix((r)) is a fixed-dose combination of pravastatin 40 mg and fenofibrate
      160 mg. The rationale for the use of Pravafenix is based on the increased
      residual cardiovascular risk observed for high-risk patients with either
      increased triglycerides or low HDL cholesterol levels despite statin monotherapy.
      This article reviews the current available information on the pharmacology,
      clinical efficacy and safety of Pravafenix. Pravafenix is recommended to be taken
      with food in the evening. In clinical trials, Pravafenix consistently produces
      complementary benefits on the overall atherogenic lipid profile of high-risk
      patients with mixed hyperlipidemia not controlled by either pravastatin 40 mg or
      simvastatin 20 mg. Within the limitations of the database, Pravafenix seems to be
      well tolerated up to 64 weeks, with an overall tolerability and safety profile
      consistent with findings generally observed with fenofibrate treatment. In
      particular, no myopathy or rhabdomyolysis has been reported. The actual European
      indication is restricted to high-risk patients with mixed hyperlipidemia whose
      LDL cholesterol levels are adequately controlled on pravastatin 40 mg
      monotherapy. Whether Pravafenix confers additional cardiovascular benefits in
      high-risk patients treated with a statin remains to be determined.

PMID- 22651834
TI  - How early is early enough to prevent stroke in atrial fibrillation?
AB  - Atrial fibrillation (AF) is a potent risk factor for stroke, being responsible
      for 20% of ischemic strokes. Subclinical AF burden has received much attention,
      especially in the context of patients with cryptogenic strokes. However, little
      is known about the impact of subclinical episodes of rapid atrial rate and the
      primary risk of stroke and systemic embolism. Healey et al. investigated whether
      subclinical rapid atrial rate detected by implanted devices was associated with
      the risk of ischemic stroke in patients without clinical evidence of AF. The
      current article discusses the potential implications of the above results.

PMID- 22651833
TI  - Fixed-dose combination therapy of candesartan cilexetil and amlodipine besilate
      for the treatment of hypertension in Japan.
AB  - Hypertension is one of the most prevalent disorders and the largest contributor
      to global mortality. The aim of antihypertensive treatment is to reduce the risk
      of cardiovascular morbidity and mortality by lowering increased blood pressure
      (BP) to target levels. Despite progress in antihypertensive drug development, BP
      control remains suboptimal. Accumulating evidence has shown that fixed-dose
      combination therapy is better in terms of BP control than increasing the dose of
      one drug or its corresponding combination. Fixed-dose combinations of an
      angiotensin receptor blocker, candesartan cilexetil, and a calcium channel
      blocker, amlodipine besilate (candesartan/amlodipine 8/2.5 or 8/5 mg), were
      approved in Japan for once-daily oral administration in hypertensive patients.
      Recent data showed that a fixed-dose combination of candesartan and amlodipine
      lowered BP safely and rapidly, providing a potential opportunity to improve the
      rate of BP control. Further studies are needed to determine whether this will
      lead to improvements in long-term clinical outcomes.

PMID- 22651835
TI  - State-of-the-art percutaneous pulmonary valve therapy.
AB  - Transcatheter pulmonary valve replacement is one of the most exciting recent
      developments in the treatment of patients with congenital heart disease and is
      being used to treat both stenotic and regurgitant valves within previously placed
      surgical conduits. Although limited somewhat by both patients and available valve
      sizes, ongoing attempts are being made to extend this technology to native right
      ventricular outflow tracts. If achieved, this will represent a significant
      advancement in attempts to prevent morbidity and mortality secondary to the
      chronic effects of right ventricular volume loading. This review deals with the
      development, current status and future endeavors of this approach.

PMID- 22651836
TI  - Stent thrombosis: an overview.
AB  - Stent thrombosis is a challenging problem following percutaneous coronary
      intervention that can lead to serious clinical consequences, such as death and
      acute myocardial infarction. Its pathophysiology is not yet completely known, and
      there are several causes suggested, such as incomplete stent endothelization,
      presence of polymers and late incomplete stent apposition. One of the main
      predictors is the early discontinuation of dual antiplatelet therapy. Stent
      improvements related to their design, with more friendly metallic platforms,
      thinner biocompatible or biodegradable polymers, absence of polymers, and even
      stents manufactured with bioabsorbable materials, could make the percutaneous
      procedure much safer and effective, allowing its application in increasingly
      complex anatomic and clinical scenarios, with low thrombosis rates.

PMID- 22651837
TI  - Stent thrombosis in patients with chronic kidney disease.
AB  - Chronic kidney disease is a strong predictor of adverse cardiac events, including
      death, myocardial infarction and stent thrombosis (ST), after percutaneous
      coronary intervention. In the past few years, the development of new therapeutic
      strategies (including both drugs and devices) and a more complete understanding
      of the pathophysiology and predictive factors of thrombosis have led to a
      significant reduction of this complication. Despite this, ST still remains a
      dramatic event due to its morbidity and mortality. Further efforts should be
      pursued to identify patients at high risk of ST in order to adopt a more
      effective preventive strategy. This review sought to examine the total weight of
      evidence regarding ST with the use of drug-eluting stents in patients with
      chronic kidney disease.

PMID- 22651838
TI  - Access-site complications and their management during transradial cardiac
      catheterization.
AB  - Transradial access for cardiac catheterization is now widely accepted among the
      invasive cardiology community as a safe and viable approach with a markedly
      reduced incidence of major access-related complications compared with the
      transfemoral approach. As this access technique is now being used more commonly
      for cardiac catheterization, it is of paramount importance to be aware of its
      complications and to understand their prevention and management. Some of the
      common complications of transradial access include asymptomatic radial artery
      occlusion, nonocclusive radial artery injury and radial artery spasm. Among these
      complications, radial artery spasm is still a significant challenge. Symptomatic
      radial arterial occlusion, pseudoaneurysm and radial artery perforation are
      rarely reported complications of the transradial approach. Early identification
      of these rare complications and their immediate management is of vital
      importance. Arteriovenous fistula, minor nerve damage and complex regional pain
      syndrome are very rare but have been reported. Recently, granulomas have been
      reported to be associated with the use of a particular brand of hydrophilic
      sheaths during the procedure. Generally, access-site complications can be
      minimized by avoiding multiple punctures, selection of smaller sheaths, gentle
      catheter manipulation, adequate anticoagulation, use of appropriate compression
      devices and avoiding prolonged high-pressure compression. In addition, careful
      observation for any ominous signs such as pain, numbness and hematoma formation
      during and in the immediate postprocedure period is essential in the prevention
      of catastrophic hand ischemia.

PMID- 22651840
TI  - Left ventricular assist devices in heart failure.
AB  - End-stage heart failure is an ever-growing and devastating disease. The median
      survival for patients with heart failure on ionotropic support alone is a meager
      6 months. Historically, the only option for these patients was to be listed for
      heart transplantation. Out of medical necessity, the idea of left ventricular
      assist device (LVAD) as a bridge to transplantation was born. Since their
      approval by the US FDA, LVADs have quadrupled the survival in patients with heart
      failure. The increase in survival has also been accompanied by decreased
      perioperative morbidity, better biocompatibility and longer device life over
      first-generation LVADs. Undoubtedly, LVADs have changed the landscape of heart
      failure treatment and will continue to do so in the foreseeable future. In this
      review, we will highlight the landmark studies that have established LVADs as a
      therapeutic option for heart failure, as well as reviewing the current LVADs
      available and speculating on the advancements that will be made in the upcoming
      years.

PMID- 22651839
TI  - Therapeutic strategies to combat neointimal hyperplasia in vascular grafts.
AB  - Neointimal hyperplasia (NIH) in bypass conduits such as veins and prosthetic
      grafts is an important clinical entity that limits the long-term success of
      vascular interventions. Although the development of NIH in the conduits shares
      many of the same features of NIH that develops in native arteries after injury,
      vascular grafts are exposed to unique circumstances that predispose them to NIH,
      including surgical trauma related to vein handling, hemodynamic changes creating
      areas of low flow, and differences in biocompatibility between the conduit and
      the host environment. Multiple different approaches, including novel surgical
      techniques and targeted gene therapies, have been developed to target and prevent
      the causes of NIH. Recently, the PREVENT trials, the first molecular biology
      trials in vascular surgery aimed at preventing NIH, have failed to produce
      improved clinical outcomes, highlighting the incomplete knowledge of the pathways
      leading to NIH in vascular grafts. In this review, we aim to summarize the
      pathophysiologic pathways that underlie the formation of NIH in both vein and
      synthetic grafts and discuss current and potential mechanical and molecular
      approaches under investigation that may limit NIH in vascular grafts.

PMID- 22651843
TI  - Band gap of carbon-sulfur [N]helicenes.
AB  - Asymmetric synthesis of (-)-[9]helicene, as well as preparation of its lower
      homologues, completes the series of carbon-sulfur [5]-, [7]-, [9]-, and
      [11]helicenes. Spectroscopic and electrochemical studies of this series provide
      an absorption onset-based band gap, E(g) = 3.40 eV, for a cross-conjugated
      (C(2)S)(n) helix; this value may be compared to E(g) = 3.59 eV obtained from TD
      DFT computed excitation energies for a series of dimethyl-substituted
      [n]helicenes (n <= 31).

PMID- 22651841
TI  - Role of biomarkers in the diagnosis and prognosis of acute kidney injury in
      patients with cardiorenal syndrome.
AB  - Cardiac and renal disease frequently coexist but have long been difficult to
      diagnose in a timely manner and treat effectively. Noninvasive and cost-effective
      biomarkers are needed to help identify cardiac patients who are at risk of acute
      kidney injury early in the course of disease. Biomarkers can provide insights
      into underlying mechanisms and lead to a better understanding of complex disease
      states such as the cardiorenal syndrome, which can lead to better therapies and,
      ultimately, to improved patient outcomes. The natriuretic peptides are
      established biomarkers in heart failure and have set the standard for how a well
      validated biomarker can be useful for diagnosis/prognosis, monitoring response to
      therapy and chronic disease management. For patients with acute kidney injury in
      the setting of cardiac disease, new biomarkers such as neutrophil gelatinase
      associated lipocalin, cystatin C, kidney injury molecule-1 and IL-18 are emerging
      as early signals of renal dysfunction prior to any elevations in serum
      creatinine. Other promising candidate biomarkers for the early diagnosis of acute
      kidney injury include osteopontin, N-acetyl-b-d-glucosaminidase, stromal cell
      derived factor-1 and exosomes. More research with all of these novel biomarkers
      is needed; however, the early results are very promising.

PMID- 22651845
TI  - Showing up channels for postinfarct ventricular tachycardia ablation.
AB  - The number of scar-related ventricular tachycardia (VT) ablation procedures is
      increasing worldwide. This is certainly due to the ever growing number of
      patients implanted with an implantable cardioverter defibrillator in whom an
      ablation procedure may be required to better control the ventricular arrhythmia
      burden, but is also likely related to our better understanding of the arrhythmias
      mechanisms as well as the improvement of the mapping techniques during the last
      15 years. Most VTs, especially those arising after myocardial infarction, depend
      on a critical isthmus. Defining precisely the critical isthmus of postinfarct VT
      may be challenging, particularly when the arrhythmia is poorly tolerated. In the
      literature, there are extensive data concerning the value of conventional
      electrophysiological techniques, especially entrainment mapping in association
      with postpacing interval measurements, regarding the identification of
      postinfarct VT isthmuses. There are, however, other--sometimes emerging-
      approaches to image critical postinfarct VT channels. We have summarized these,
      reviewing data from the published literature as well as our own experience.

PMID- 22651844
TI  - Fluid overload and changes in serum creatinine after cardiac surgery: predictors
      of mortality and longer intensive care stay. A prospective cohort study.
AB  - INTRODUCTION: Fluid overload is a clinical problem frequently related to cardiac
      and renal dysfunction. The aim of this study was to evaluate fluid overload and
      changes in serum creatinine as predictors of cardiovascular mortality and
      morbidity after cardiac surgery. METHODS: Patients submitted to heart surgery
      were prospectively enrolled in this study from September 2010 through August
      2011. Clinical and laboratory data were collected from each patient at
      preoperative and trans-operative moments and fluid overload and creatinine levels
      were recorded daily after cardiac surgery during their ICU stay. Fluid overload
      was calculated according to the following formula: (Sum of daily fluid received
      (L)--total amount of fluid eliminated (L)/preoperative weight (kg) * 100).
      Preoperative demographic and risk indicators, intra-operative parameters and
      postoperative information were obtained from medical records. Patients were
      monitored from surgery until death or discharge from the ICU. We also evaluated
      the survival status at discharge from the ICU and the length of ICU stay (days)
      of each patient. RESULTS: A total of 502 patients were enrolled in this study.
      Both fluid overload and changes in serum creatinine correlated with mortality
      (odds ratio (OR) 1.59; confidence interval (CI): 95% 1.18 to 2.14, P = 0.002 and
      OR 2.91; CI: 95% 1.92 to 4.40, P <0.001, respectively). Fluid overload played a
      more important role in the length of intensive care stay than changes in serum
      creatinine. Fluid overload (%): b coefficient = 0.17; beta coefficient = 0.55, P
      <0.001); change in creatinine (mg/dL): b coefficient = 0.01; beta coefficient =
      0.11, P = 0.003). CONCLUSIONS: Although both fluid overload and changes in serum
      creatinine are prognostic markers after cardiac surgery, it seems that
      progressive fluid overload may be an earlier and more sensitive marker of renal
      dysfunction affecting heart function and, as such, it would allow earlier
      intervention and more effective control in post cardiac surgery patients.

PMID- 22651846
TI  - Application of affinity selection-mass spectrometry assays to purification and
      affinity-based screening of the chemokine receptor CXCR4.
AB  - Affinity selection-mass spectrometry (AS-MS) is a sensitive technology for
      identifying small molecules that bind to target proteins, and assays enabled by
      AS-MS can be used to delineate relative binding affinities of ligands for
      proteins. 'Indirect' AS-MS assays employ size-exclusion techniques to separate
      target-ligand complexes from unbound ligands, and target-associated ligands are
      then specifically detected by liquid chromatography mass spectrometry. We report
      how indirect AS-MS binding assays with known reference control compounds were
      used as guideposts for development of an optimized purification method for CXCR4,
      a G-protein coupled chemokine receptor, for which we sought novel antagonists.
      The CXCR4 purification method that was developed was amenable to scale-up and
      enabled the screening of purified recombinant human CXCR4 against a large
      combinatorial library of small molecules by high throughput indirect AS-MS. The
      screen resulted in the discovery of new ligands that competed off binding of
      reference compounds to CXCR4 in AS-MS binding assays and that antagonized
      SDF1alpha-triggered responses and CXCR4-mediated HIV1 viral uptake in cell-based
      assays. This report provides a methodological paradigm whereby indirect AS-MS
      based ligand binding assays may be used to guide optimal integral membrane
      protein purification methods that enable downstream affinity selection-based
      applications such as high throughput AS-MS screens.

PMID- 22651848
TI  - Effect of L-arginine supplement on liver regeneration after partial hepatectomy
      in rats.
AB  - BACKGROUND: Nitric oxide (NO) has been reported to be a key mediator in
      hepatocyte proliferation during liver regeneration. NO is the oxidative
      metabolite of L-arginine, and is produced by a family of enzymes, collective
      termed nitric oxide synthase (NOS). Thus, administration of L-arginine might
      enhance liver regeneration after a hepatectomy. Another amino acid, L-glutamine,
      which plays an important role in catabolic states and is a crucial factor in
      various cellular and organ functions, is widely known to enhance liver
      regeneration experimentally. Thus, the present study was undertaken to evaluate
      the effects of an L-arginine supplement on liver regeneration, and to compared
      this with supplementation with L-glutamine and L-alanine (the latter as a
      negative control), using a rat partial hepatectomy model. METHODS: Before and
      after a 70% hepatectomy, rats received one of three amino acid solutions (L
      arginine, L-glutamine, or L-alanine). The effects on liver regeneration of the
      administered solutions were examined by assessment of restituted liver mass,
      staining for proliferating cell nuclear antigen (PCNA), and total RNA and DNA
      content 24 and 72 hours after the operation. RESULTS: At 72 hours after the
      hepatectomy, the restituted liver mass, the PCNA labeling index and the DNA
      quantity were all significantly higher in the L-arginine and L-glutamine groups
      than in the control. There were no significant differences in those parameters
      between the L-arginine and L-glutamine groups, nor were any significant
      differences found between the L-alanine group and the control. CONCLUSION: Oral
      supplements of L-arginine and L-glutamine enhanced liver regeneration after
      hepatectomy in rats, suggesting that an oral arginine supplement can clinically
      improve recovery after a major liver resection.

PMID- 22651847
TI  - Liposomal clodronate selectively eliminates microglia from primary astrocyte
      cultures.
AB  - BACKGROUND: There is increasing interest in astrocyte biology because astrocytes
      have been demonstrated to play prominent roles in physiological and pathological
      conditions of the central nervous system, including neuroinflammation. To
      understand astrocyte biology, primary astrocyte cultures are most commonly used
      because of the direct accessibility of astrocytes in this system. However, this
      advantage can be hindered by microglial contamination. Although several authors
      have warned regarding microglial contamination in this system, complete
      microglial elimination has never been achieved. METHODS: The number and
      proliferative potential of contaminating microglia in primary astrocyte cultures
      were quantitatively assessed by immunocytologic and flow cytometric analyses. To
      examine the utility of clodronate for microglial elimination, primary astrocyte
      cultures or MG-5 cells were exposed to liposomal or free clodronate, and then
      immunocytologic, flow cytometric, and gene expression analyses were performed.
      The gene expression profiles of microglia-eliminated and microglia-contaminated
      cultures were compared after interleukin-6 (IL-6) stimulation. RESULTS: The
      percentage of contaminating microglia exceeded 15% and continued to increase
      because of their high proliferative activity in conventional primary astrocyte
      cultures. These contaminating microglia were selectively eliminated low
      concentration of liposomal clodronate. Although primary microglia and MG-5 cells
      were killed by both liposomal and free clodronate, free clodronate significantly
      affected the viability of astrocytes. In contrast, liposomal clodronate
      selectively eliminated microglia without affecting the viability, proliferation
      or activation of astrocytes. The efficacy of liposomal clodronate was much higher
      than that of previously reported methods used for decreasing microglial
      contamination. Furthermore, we observed rapid tumor necrosis factor-alpha and IL
      1b gene induction in conventional primary astrocyte cultures after IL-6
      stimulation, which was due to the activation of the Janus kinase/signal
      transducer and activator of the transcription pathway in contaminating microglia.
      CONCLUSIONS: Because contaminating microglia could result in erroneous data
      regarding the pro-inflammatory properties of astrocytes, astrocyte biology should
      be studied in the absence of microglial contamination. Our simple method will be
      widely applicable to experimental studies of astrocyte biology and provide clues
      for understanding the role of astrocytes in neural development, function and
      disease.

PMID- 22651850
TI  - IgA antibodies against tissue transglutaminase, endomysium and gliadin in
      idiopathic polyneuropathy.
AB  - OBJECTIVES: To study the prevalence of antibodies of IgA class against tissue
      transglutaminase (tTG), endomysium (EMA) and gliadin (AGA) in patients with
      chronic idiopathic axonal polyneuropathy (CIAP) and to characterize the patients
      clinically and neurophysiologically. METHODS: Of 182 patients, 126 patients
      agreed to blood sampling. Sera were analysed by ELISAs detecting anti-tTG and
      AGA, whereas EMA was analysed by indirect immunofluorescence (IF) microscopy.
      Gastrointestinal symptoms were assessed by data from medical records and patient
      interviews. RESULTS: Nine of 126 patients (7%) were seropositive in at least one
      test (five with positive anti-tTG and/or EMA and four with positive AGA only).
      One patient with elevated levels of all specificities had laboratory signs of
      malabsorption and gastrointestinal complaints with abdominal pain and diarrhoea.
      CONCLUSIONS: Elevated levels of IgA-AGA were slightly more frequent in patients
      with CIAP (4%) compared to 2.5% in 1866 healthy blood donors. Highly specific
      serological markers indicative of coeliac disease (CD) (anti-tTG and EMA) were
      somewhat more common in our patients with CIAP (4%) than expected from normal
      reference values and from studies of the prevalence of CD in the general
      population. Even though these findings may indicate a relationship, the
      aetiological importance is unclear.

PMID- 22651849
TI  - Alcohol use predicts ER visits in individuals with alpha-1 antitrypsin deficiency
      (AATD) associated COPD.
AB  - Excessive alcohol use in COPD has been associated with increased mortality;
      however, little is known about alcohol use in AATD-associated COPD. A total of
      538 individuals with AATD-associated COPD completed questionnaires at baseline
      and 330 also completed 2 years of follow-up questionnaires. Demographic and
      health information was collected, including information about alcohol use, ER
      visits for COPD, and hospitalizations for COPD. Problem alcohol use was
      characterized using the CAGE screening questionnaire and recent alcohol
      consumption. Demographic and clinical characteristics associated with problem
      drinking were identified using logistic regression. Problem drinking at baseline
      was examined as a predictor of ER visits and hospital admissions for COPD in the
      subsequent two years using logistic regression adjusting for demographic
      variables and baseline health status. 14% of the sample reported a history of
      problem drinking per the CAGE and 8% reported problem drinking in the past week.
      Problem drinking was associated with higher education and greater lifetime
      tobacco exposure. Recent alcohol consumption was a significant predictor of
      having an ER visit for COPD in the subsequent two years. Compared to individuals
      who reported problem drinking in the past week, individuals with no consumption
      (OR = 0.32, 95% CI = 0.10 to 0.97, p = .043) and individuals with low-to-moderate
      consumption (OR = 0.25, 95% CI = 0.08 to 0.77, p = .016) had significantly lower
      odds of an ER visit. Neither measure of problem drinking predicted hospital
      admission. Screening for recent excessive alcohol use in this population may
      identify individuals at risk for use of costly emergency health services.

PMID- 22651852
TI  - Functional and patient-reported outcomes in symptomatic lumbar spinal stenosis
      following percutaneous decompression.
AB  - BACKGROUND: Neurogenic claudication due to symptomatic lumbar spinal stenosis
      (LSS) is a painful condition causing significant functional disability. While the
      cause of LSS is multifactorial, thickened ligamentum flavum (LF) accounts for up
      to 85% of spinal canal narrowing. mild percutaneous lumbar decompression allows
      debulking of the hypertrophic LF while avoiding the morbidities frequently
      associated with more invasive surgical procedures. METHODS: In this prospective
      case series study, consecutive LSS patients presenting with neurogenic
      claudication were treated with percutaneous lumbar decompression. Efficacy was
      evaluated using the Pain Disability Index (PDI) and Roland-Morris Disability
      Questionnaire. Pre- and postprocedure Standing Time, Walking Distance, and Visual
      Analog Score (VAS) were also monitored. Significant device- or procedure-related
      adverse events were reported. RESULTS: The mild procedure was successfully
      performed on forty patients. At twelve months, both PDI and Roland-Morris showed
      significant improvement of 22.6 points (ANOVA, P<0.0001) and 7.7 points (ANOVA,
      P<0.0001), respectively. Walking Distance, Standing Time, and VAS improvements
      were also statistically significant, increasing from 246 to 3,956 feet (ANOVA,
      P<0.0001), 8 to 56 minutes (ANOVA, P<0.0001), and 7.1 to 3.6 points (ANOVA,
      P<0.0001), respectively. Tukey HSD test found improvement in all 5-outcome
      measures to be significant from baseline at each follow-up interval. No
      significant device- or procedure-related adverse events were reported.
      CONCLUSION: This study demonstrated significant functional improvement as well as
      decreased disability secondary to neurogenic claudication after mild procedure.
      Safety, cost-effectiveness, and quality-of-life outcomes are best compared with
      comprehensive medical management in a randomized controlled fashion and, where
      ethical, to open lumbar decompression surgery.

PMID- 22651851
TI  - Role of DNA base excision repair in the mutability and virulence of Streptococcus
      mutans.
AB  - The oral pathogen, Streptococcus mutans, possesses inducible DNA repair defences
      for protection against pH fluctuations and production of reactive oxygen
      metabolites such as hydrogen peroxide (H(2) O(2) ), which are present in the oral
      cavity. DNA base excision repair (BER) has a critical role in genome maintenance
      by preventing the accumulation of mutations associated with environmental factors
      and normal products of cellular metabolism. In this study, we examined the
      consequences of compromising the DNA glycosylases (Fpg and MutY) and
      endonucleases (Smx and Smn) of the BER pathway and their relative role in
      adaptation and virulence. Enzymatic characterization of the BER system showed
      that it protects the organism against the effects of the highly mutagenic lesion,
      7,8-dihydro-8-oxo-2'-deoxyguanine (8-oxo-dG). S. mutans strains lacking a
      functional Fpg, MutY or Smn showed elevated spontaneous mutation frequencies;
      and, these mutator phenotypes correlated with the ability of the strains to
      survive killing by acid and oxidative agents. In addition, in the Galleria
      mellonella virulence model, strains of S. mutans deficient in Fpg, MutY and Smn
      showed increased virulence as compared with the parent strain. Our results
      suggest that, for S. mutans, mutator phenotypes, due to loss of BER enzymes, may
      confer an advantage to virulence of the organism.

PMID- 22651853
TI  - Effects of miltefosine on the proliferation, ultrastructure, and phospholipid
      composition of Angomonas deanei, a trypanosomatid protozoan that harbors a
      symbiotic bacterium.
AB  - Some trypanosomatids, such as Angomonas deanei formerly named as Crithidia
      deanei, present an obligatory intracellular bacterium, which maintains a
      mutualistic relationship with the host. Phosphatidylcholine (PC) is the major
      phospholipid in eukaryotes and an essential component of cell membranes playing
      structural, biochemical, and physiological roles. However, in prokaryotes, PC is
      present only in those species closely associated with eukaryotes, either in
      symbiotic or pathogenic interactions. In trypanosomatids, the endosymbiont
      envelope is composed by a reduced cell wall and by two membrane units that lack
      sterols and present cardiolipin (CL) and PC as the major phospholipids. In this
      study, we tested the effects of miltefosine in A. deanei proliferation, as well
      as, on the ultrastrucuture and phospholipid composition considering that this
      drug inhibits the CTP-phosphocholine cytidyltransferase (CCT), a key enzyme in
      the PC biosynthesis. Besides the low effect of miltefosine in cellular
      proliferation, treated protozoa presented ultrastructural alterations such as
      plasma membrane shedding and blebbing, mitochondrial swelling, and convolutions
      of the endosymbiont envelope. The use of (32) Pi as a tracer revealed that the
      production of PC, CL, and phosphatidylethanolamine decreased while
      phosphatidylinositol production remained stable. Mitochondrion and symbiont
      fractions obtained from protozoa treated with miltefosine also presented a
      decrease in phospholipid production, reinforcing the idea that an intensive
      metabolic exchange occurs between the host trypanosomatid and structures of
      symbiotic origin.

PMID- 22651854
TI  - Age-expanded normative data for the Ruff 2&7 Selective Attention Test: evaluating
      cognition in older males.
AB  - The Ruff 2&7 Selective Attention Test's (RSAT) current scoring data are
      relatively limited for older adults because persons over the age of 70 years were
      not included in the normative sample. Prior evidence suggests that changes in
      attention skills, such as those evaluated by the RSAT, may distinguish normal
      cognitive aging from pathologic cognitive decline. Thus normative data for older
      individuals on this measure increase its utility in diagnosing Mild Cognitive
      Impairment (MCI) and dementia, and enhance its potential use in clinical and
      research settings. Data from 415 male volunteers (mean age = 69.5 +/- 5.7 years)
      in the PREADViSE clinical trial were used in the current investigation. Analysis
      of covariance (ANCOVA) shows statistically significant effects of age, race, and
      education on RSAT Speed measures. Results indicate that age-expanded norms will
      provide a more accurate reflection of the typical performance of older
      individuals on the RSAT.

PMID- 22651858
TI  - Synthesis and pharmacological evaluation of 2,4-dinitroaryldithiocarbamate
      derivatives as novel monoacylglycerol lipase inhibitors.
AB  - Monoacylglycerol lipase (MAGL) is responsible for signal termination of 2
      arachidonoylglycerol (2-AG), an endocannabinoid neurotransmitter endowed with
      several physiological effects. Previously, we showed that the arylthioamide
      scaffold represents a privileged template for designing MAGL inhibitors. A series
      of 37 compounds resulting from pharmacomodulations around the arylthioamide
      template were synthesized and tested to evaluate their inhibitory potential on
      MAGL activity as well as their selectivity over fatty acid amide hydrolase
      (FAAH), another endocannabinoid-hydrolyzing enzyme. We have identified 2,4
      dinitroaryldithiocarbamate derivatives as a novel class of MAGL inhibitors. Among
      the synthesized compounds, we identified [2,4-dinitrophenyl-4-(4-tert
      butylbenzyl)piperazine-1-carbodithioate] (CK37), as the most potent MAGL
      inhibitor within this series (IC(50) = 154 nM). We have also identified [2,4
      dinitrophenyl-4-benzhydrylpiperazine-1-carbodithioate] (CK16) as a selective MAGL
      inhibitor. These compounds are irreversible MAGL inhibitors that probably act by
      interacting with Cys208 or Cys242 and Ser122 residues of the enzyme. Moreover,
      CK37 is able to raise 2-arachidonoylglycerol (2-AG) levels in intact cells.

PMID- 22651857
TI  - Temporal association of stress sensitivity and symptoms in individuals at
      clinical high risk for psychosis.
AB  - BACKGROUND: Increased sensitivity and exposure to stress are associated with
      psychotic symptoms in schizophrenia and its risk states, but little is known
      about the co-evolution of stress sensitivity and exposure with positive and other
      symptoms in a clinical high-risk (CHR) cohort. METHOD: A combined cross-sectional
      and longitudinal design was used to examine the associations over time of stress
      sensitivity and exposure (i.e. life events) with 'prodromal' symptoms in a cohort
      of 65 CHR patients assessed quarterly for up to 4 years, and at baseline in 24
      healthy controls similar in age and gender. RESULTS: Impaired stress tolerance
      was greater in patients, in whom it was associated over time with positive and
      negative symptoms, in addition to depression, anxiety and poor function. By
      contrast, life events were comparable in patients and controls, and bore no
      association with symptoms. In this treated cohort, there was a trajectory of
      improvement in stress tolerance, symptoms and function over time. CONCLUSIONS:
      Impaired stress tolerance was associated with a wide range of 'prodromal'
      symptoms, consistent with it being a core feature of the psychosis risk state.
      Self-reported life events were not relevant as a correlate of clinical status. As
      in other treated CHR cohorts, most patients improved over time across symptom
      domains.

PMID- 22651859
TI  - Chibby suppresses growth of human SW480 colon adenocarcinoma cells through
      inhibition of beta-catenin signaling.
AB  - The canonical Wnt signaling pathway is crucial for embryonic development and
      adult tissue homeostasis. Activating mutations in the Wnt pathway are frequently
      associated with the pathogenesis of various types of cancer, particularly colon
      cancer. Upon Wnt stimulation, beta-catenin plays a central role as a coactivator
      through direct interaction with Tcf/Lef transcription factors to stimulate target
      gene expression. We have previously shown that the evolutionarily conserved
      protein Chibby (Cby) physically binds to beta-catenin to repress beta-catenin
      dependent gene activation by 1) competing with Tcf/Lef factors for binding to
      beta-catenin and 2) facilitating nuclear export of beta-catenin via interaction
      with 14-3-3 proteins. In this study, we employed human colon adenocarcinoma SW480
      cells with high levels of endogenous beta-catenin to address a potential tumor
      suppressor role of Cby. In SW480 stable cells expressing wild-type Cby (CbyWT),
      but not 14-3-3-binding- defective Cby mutant CbyS20A, a significant fraction of
      endogenous beta-catenin was detected in the cytoplasm. Consistent with this,
      CbyWT-expressing cells showed low levels of beta-catenin signaling activity,
      leading to reduced growth. Our results suggest that Cby, in collaboration with 14
      3-3 proteins, can counteract oncogenic beta-catenin signaling in colon cancer
      cells.

PMID- 22651860
TI  - Proteome dynamics and early salt stress response of the photosynthetic organism
      Chlamydomonas reinhardtii.
AB  - BACKGROUND: The cellular proteome and metabolome are underlying dynamic
      regulation allowing rapid adaptation to changes in the environment. System-wide
      analysis of these dynamics will provide novel insights into mechanisms of stress
      adaptation for higher photosynthetic organisms. We applied pulsed-SILAC labeling
      to a photosynthetic organism for the first time and we established a method to
      study proteome dynamics in the green alga Chlamydomonas reinhardtii, an emerging
      model system for plant biology. In addition, we combined the analysis of protein
      synthesis with metabolic profiling to study the dynamic changes of metabolism and
      proteome turnover under salt stress conditions. RESULTS: To study de novo protein
      synthesis an arginine auxotroph Chlamydomonas strain was cultivated in presence
      of stable isotope-labeled arginine for 24 hours. From the time course experiment
      in 3 salt concentrations we could identify more than 2500 proteins and their H/L
      ratio in at least one experimental condition; for 998 protiens at least 3 ratio
      counts were detected in the 24 h time point (0 mM NaCl). After fractionation we
      could identify 3115 proteins and for 1765 of them we determined their de novo
      synthesis rate. Consistently with previous findings we showed that RuBisCO is
      among the most prominent proteins in the cell; and similar abundance and turnover
      for the small and large RuBisCO subunit could be calculated. The D1 protein was
      identified among proteins with a high synthesis rates. A global median half-life
      of 45 h was calculated for Chlamydomonas proteins under the chosen conditions.
      CONCLUSION: To investigate the temporal co-regulation of the proteome and
      metabolome, we applied salt stress to Chlamydomonas and studied the time
      dependent regulation of protein expression and changes in the metabolome. The
      main metabolic response to salt stress was observed within the amino acid
      metabolism. In particular, proline was up-regulated manifold and according to
      that an increased carbon flow within the proline biosynthetic pathway could be
      measured. In parallel the analysis of abundance and de novo synthesis of the
      corresponding enzymes revealed that metabolic rearrangements precede adjustments
      of protein abundance.

PMID- 22651862
TI  - In-stent neoatherosclerosis: a final common pathway of late stent failure.
AB  - Percutaneous coronary intervention with stenting is the most widely performed
      procedure for the treatment of symptomatic coronary disease, and drug-eluting
      stents (DES) have minimized the limitations of bare-metal stents (BMS).
      Nevertheless, there remain serious concerns about late complications such as in
      stent restenosis and late stent thrombosis. Although in-stent restenosis of BMS
      was considered as a stable condition with an early peak of intimal hyperplasia,
      followed by a regression period beyond 1 year, recent studies have reported that
      one-third of patients with in-stent restenosis of BMS presented with acute
      coronary syndrome that is not regarded as clinically benign. Furthermore, both
      clinical and histologic studies of DES have demonstrated evidence of continuous
      neointimal growth during long-term follow-up, which is designated as "late catch
      up" phenomenon. Here, we present emerging evidence of de novo neoatherosclerosis
      based on histology, angioscopy, and intravascular images that provide a new
      insight for the mechanism of late stent failure. In-stent neoatherosclerosis is
      an important substrate for late stent failure for both BMS and DES, especially in
      the extended phase. In light of the rapid progression in DES, early detection of
      neoatherosclerosis may be beneficial to improving long-term outcome of patients
      with DES implants.

PMID- 22651861
TI  - Suzuki-Miyaura cross-coupling reactions of potassium Boc-protected
      aminomethyltrifluoroborate with aryl and hetaryl mesylates.
AB  - Palladium-catalyzed Suzuki-Miyaura cross-coupling reactions were studied with
      potassium Boc-protected aminomethyltrifluoroborate through C-O activation of
      various mesylate derivatives to afford the corresponding products in moderate to
      good yields.

PMID- 22651863
TI  - Applicability of a risk score for prediction of the long-term (8-year) benefit of
      the implantable cardioverter-defibrillator.
AB  - OBJECTIVES: The present study was designed to explore the 8-year survival benefit
      of a nonresynchronization implantable cardioverter-defibrillator (ICD) according
      to a simple risk stratification score. BACKGROUND: There is limited information
      regarding factors that predict the benefit of primary prevention with an ICD
      during long-term follow-up. METHODS: This study used a previously developed risk
      score including 5 clinical factors (New York Heart Association functional class
      >II, age >70 years, blood urea nitrogen >26 mg/dl, QRS duration >0.12 s, and
      atrial fibrillation) to evaluate 8-year ICD survival benefit within risk score
      categories among 1,191 MADIT-II (Multicenter Automatic Defibrillator Implantation
      Trial II) patients. RESULTS: Patients with low (0 risk factors, n = 345) and
      intermediate risk (1 to 2 risk factors, n = 646) demonstrated a significantly
      higher probability of survival at 8-year follow-up when treated by ICD as
      compared with non-ICD therapy (75% vs. 58%, p = 0.004; and 47% vs. 31%, p <
      0.001, respectively). By contrast, among high-risk patients (3 or more risk
      factors, n = 200), there was no significant difference in 8-year survival between
      the ICD and non-ICD subgroups (19% vs. 17%, p = 0.50). Consistently, multivariate
      analysis showed that ICD therapy was associated with a significant long-term
      survival benefit among low- and intermediate-risk patients (hazard ratio [HR]:
      0.52, p < 0.001, and HR: 0.66, p < 0.001, respectively), whereas treatment with
      an ICD was not associated with a significant benefit among high-risk patients
      (HR: 0.84, p = 0.25). CONCLUSIONS: These findings suggest that a simple risk
      score can identify patients who derive significant long-term benefit from primary
      ICD therapy. High-risk patients with multiple comorbidities composed 17% of the
      MADIT-II population and did not derive long-term benefit from
      nonresynchronization device therapy.

PMID- 22651865
TI  - Diabetes and vascular (18)f-fluorodeoxyglucose positron emission tomography
      uptake: another step toward understanding inflammation in atherosclerosis.

PMID- 22651864
TI  - Impact of noninsulin-dependent type 2 diabetes on carotid wall 18F
      fluorodeoxyglucose positron emission tomography uptake.
AB  - OBJECTIVES: In this study, the impact of noninsulin-dependent type 2 diabetes
      mellitus on carotid wall (18)F-fluorodeoxyglucose (FDG) uptake in patients with
      documented or suspected cardiovascular disease was evaluated. BACKGROUND:
      Inflammation is a pivotal process in the progression of atherosclerosis, which
      can be noninvasively imaged by FDG positron emission tomography (FDG-PET).
      METHODS: Carotid artery wall FDG uptake was quantified in 134 patients (age 60.2
      +/- 9.7 years; diabetic subjects, n = 43). The pre-scan glucose (gluc) level
      corrected mean of the maximum standardized uptake value (SUV) values
      ((mean)SUV(gluc)), mean of the maximum target-to-background ratio
      ((mean)TBR(gluc)), and single hottest segment (SHS(gluc)) of FDG uptake in the
      artery wall were calculated. Associations between FDG uptake, the presence of
      risk factors for atherosclerosis, and diabetes were then assessed by multiple
      regression analysis with backward elimination. RESULTS: The study demonstrated a
      significant association between diabetes and FDG uptake in the arterial wall
      (diabetes (mean)SUV(gluc) beta = 0.324, (mean)TBR(gluc) beta = 0.317, and
      SHS(gluc) beta = 0.298; for all, p < 0.0001). In addition, in diabetic patients,
      both body mass index >= 30 kg/m(2) ((mean)SUV(gluc) beta = 0.4, (mean)TBR(gluc)
      beta = 0.357, and SHS(gluc) beta = 0.388; for all, p < 0.015) and smoking
      ((mean)TBR(gluc), beta = 0.312; SHS(gluc), beta = 0.324; for all, p < 0.04) were
      significantly associated with FDG uptake. CONCLUSIONS: Type 2 diabetes was
      significantly associated with carotid wall FDG uptake in patients with known or
      suspected cardiovascular disease. In diabetic patients, obesity and smoking add
      to the risk of increased FDG uptake values.

PMID- 22651866
TI  - Evaluation of patients with possible cardiac chest pain: a way out of the jungle.

PMID- 22651867
TI  - Outcome of cardiac surgery in patients 50 years of age or older with Ebstein
      anomaly: survival and functional improvement.
AB  - OBJECTIVES: This study sought to analyze the presentation, surgical procedures,
      and outcomes in patients >= 50 years of age with Ebstein anomaly (EA).
      BACKGROUND: Data on management and surgical outcomes in older patients with EA
      are limited. METHODS: Operative and clinical data from patients with EA >= 50
      years of age undergoing cardiac surgery at our center between October 1980 and
      January 2010 were analyzed. RESULTS: During the study period, 89 procedures were
      performed in 81 patients with EA (63% women; mean [range] age 59 [50 to 79]
      years). Pre-operative symptoms included palpitations (n = 69), edema (n = 30),
      and previous stroke/transient ischemic attack (n = 21). Seventy-six patients
      (85%) had functional class III or IV symptoms, and 13 (16%) had previous cardiac
      surgery. Tricuspid valve surgery was necessary in 87 of the 89 procedures (98%):
      replacement in 65 (73%) and repair in 22 (25%). Three early deaths occurred (4%).
      On long-term follow-up (available in 73 of 78 early survivors), 63 patients (89%)
      had improved functional class and 13 patients died (19%). The 20-year survival
      was 65% versus 74% for age- and sex-matched controls (p = 0.001). The best
      predictors of late death were lack of post-operative improvement and older age at
      surgery. CONCLUSIONS: Although cardiac surgery in patients with EA >= 50 years of
      age was often complex, early mortality was low (4%) when surgery was performed at
      an experienced center. Long-term survival was good, although less than expected.
      These data suggested that surgery in older patients with EA may have to be
      performed earlier.

PMID- 22651868
TI  - Micro-RNA-34a contributes to the impaired function of bone marrow-derived
      mononuclear cells from patients with cardiovascular disease.
AB  - OBJECTIVES: This study evaluated the regulation and function of micro-RNAs (miRs)
      in bone marrow-mononuclear cells (BMCs). BACKGROUND: Although cell therapy with
      BMCs may represent a therapeutic option to treat patients with heart disease, the
      impaired functionality of patient-derived cells remains a major challenge. Small
      noncoding miRs post-transcriptionally control gene expression patterns and play
      crucial roles in modulating cell survival and function. METHODS: Micro-RNAs were
      detected by miR profiling in BMCs isolated from healthy volunteers (n = 6) or
      from patients with myocardial infarction (n = 6), and the results were confirmed
      by polymerase chain reaction (PCR) in a larger cohort (n = 37). The function of
      selected miRs was determined by gain-of-function studies in vitro and by locked
      nuclear acid (LNA) modified inhibitors in vitro and in vivo. RESULTS: We
      identified several miRs that are up-regulated in BMCs from patients with
      myocardial infarction compared with BMCs from healthy controls, including the pro
      apoptotic and antiproliferative miR-34a and the hypoxia-controlled miR-210.
      Inhibition of miR-34 by LNA-34a significantly reduced miR-34a expression and
      blocked hydrogen peroxide-induced cell death of BMC in vitro, whereas
      overexpression of miR-34a reduced the survival of BMCs in vitro. Pre-treatment of
      BMCs with LNA-34a ex vivo significantly increased the therapeutic benefit of
      transplanted BMCs in mice after acute myocardial infarction (AMI). CONCLUSIONS:
      These results demonstrate that cardiovascular disease modulates the miR
      expression of BMCs in humans. Reducing the expression of the pro-apoptotic miR
      34a improves the survival of BMCs in vitro and enhances the therapeutic benefit
      of cell therapy in mice after AMI.

PMID- 22651869
TI  - Dead man walking: an extreme case of sinusoidal wave pattern in severe
      hyperkalemia.

PMID- 22651870
TI  - President's Page: Restoring the Patient-Physician Relationship.

PMID- 22651871
TI  - Cutoffs for intervention for asymptomatic severe aortic stenosis.

PMID- 22651872
TI  - Aortic stenosis: new classification.

PMID- 22651875
TI  - A swinging pacemaker lead promoting endocarditis and severe tricuspid
      regurgitation.

PMID- 22651877
TI  - Gender impact on prognosis of acute coronary syndrome patients treated with drug
      eluting stents.
AB  - Women have a higher risk of adverse outcomes after percutaneous coronary
      intervention (PCI) than men. However, in acute coronary syndrome (ACS), long-term
      outcomes after contemporary PCI with drug-eluting stent (DES) have not been fully
      investigated. We aimed to test the impact of gender on outcomes in patients with
      ACS after PCI with DES. We analyzed all patients with ACS from the prospective
      NOBORI-2 trial who underwent PCI with a Nobori DES from 2008 through 2009 in 125
      centers worldwide. End points of the study were target lesion failure, cardiac
      death, myocardial infarction (MI), and clinically driven target lesion
      revascularization, and major adverse cardiac events (composite of cardiac death,
      MI, and target vessel revascularization) at 1 year and yearly up to 5 years.
      There were 1,640 patients with ACS, 1,268 men (77%) and 372 women (23%). Compared
      to men, women were 5 years older and more frequently had co-morbidities such as
      diabetes mellitus and hypertension. There were no gender differences for cardiac
      death (1.3% vs 2.7%), MI (2.1% vs 3.2%), or target lesion revascularization (2.6%
      vs 3.8%) at 1 year after the procedure for men and women, respectively. The trend
      was the same at 2 years (cardiac death 2.0% vs 2.3%, MI 2.5% vs 3.5%, target
      lesion revascularization 3.2% vs 4.6%). Target lesion failure rates were 4.5% and
      5.9% at 1 year and 5.7% and 7.3% at 2 years in men and women, respectively (p =
      NS). Multivariate analysis, which included age, hypertension, diabetes mellitus,
      and number of diseased vessels, showed that gender was not a predictor for
      outcome. There were no differences in bleeding or stent thrombosis rates. Relief
      from anginal symptoms was similar. The same rate of adherence to dual
      antiplatelet therapy was observed and reached 73% at 1 year and 31% at 2 years
      after the ACS event and PCI. In conclusion, although women had worse baseline
      characteristics, no differences in outcomes were observed between men and women
      treated for ACS with contemporary DES.

PMID- 22651878
TI  - Development of a consensus document to improve multireader concordance and
      accuracy of aortic regurgitation severity grading by echocardiography versus
      cardiac magnetic resonance imaging.
AB  - Current guidelines recommend a multiparametric echocardiographic assessment of
      aortic regurgitation (AR). However, the absence of a hierarchical weighting of
      discordant parameters could cause interobserver variability. In the present
      study, we sought to define and improve the interobserver variability of AR
      assessment. Seventeen level 3 readers graded 20 randomly selected patients with
      AR. The readers also provided a usefulness score for each parameter, depending on
      its influence on their decision of the AR severity grade. A consensus strategy
      was subsequently formulated and validated against cardiac magnetic resonance
      imaging in a separate group of 80 patients. The readers were updated with the
      consensus document and recalibrated using the same cases. Agreement was
      statistically assessed using Randolph's free-marginal multirater kappa. At
      baseline, no uniform approach was used to combine the individual parameters,
      contributing to the interobserver variability (overall kappa 0.5). A consensus
      strategy to categorize AR severity was developed in which the left ventricular
      volume took precedence over the other parameters and was used to differentiate
      chronic severe AR from less severe categories. Recalibration of the readers using
      this consensus strategy improved concordance (kappa increased to 0.7). The new
      strategy also improved the accuracy relative to cardiac magnetic resonance
      imaging, as evidenced by full agreement on severe AR between the consensus
      document-based grading and AR severity defined by cardiac magnetic resonance
      imaging in the separate validation group of 80 patients. In conclusion, grading
      of chronic AR using a multiparametric approach has suboptimal consistency between
      readers and a left ventricular volume-based consensus document improved
      concordance and accuracy.

PMID- 22651876
TI  - Comparison of the feasibility and effectiveness of transradial coronary
      angiography via right versus left radial artery approaches (from the PREVAIL
      Study).
AB  - It remains undefined if transradial coronary angiography from a right or left
      radial arterial approach differs in real-world practice. To address this issue,
      we performed a subanalysis of the PREVAIL study. The PREVAIL study was a
      prospective, multicenter, observational survey of unselected consecutive patients
      undergoing invasive cardiovascular procedures over a 1-month observation period,
      specifically aimed at assessing the outcomes of radial approach in the
      contemporary real world. The choice of arterial approach was left to the
      discretion of the operator. Prespecified end points of this subanalysis were
      procedural characteristics. Of 1,052 patients consecutively enrolled, 509
      patients underwent transradial catheterization, 304 with a right radial and 205
      with a left radial approach. Procedural success rates were similar between the 2
      groups. Compared to the left radial group, the right radial group had longer
      procedure duration (46 +/- 29 vs 33 +/- 24 minutes, p <0.0001) and fluoroscopy
      time (765 +/- 787 vs 533 +/- 502, p <0.0001). At multivariate analysis, including
      a parsimonious propensity score for the choice of left radial approach, duration
      of procedure (beta coefficient 11.38, p <0.001) and total dose-area product (beta
      coefficient 11.38, p <0.001) were independently associated with the choice of the
      left radial artery approach. The operator's proficiency in right/left radial
      approach did not influence study results. In conclusion, right and left radial
      approaches are feasible and effective to perform percutaneous procedures. In the
      contemporary real world, however, the left radial route is associated with
      shorter procedures and lower radiologic exposure than the right radial approach,
      independently of an operator's proficiency.

PMID- 22651879
TI  - Right ventricular dysfunction and exercise capacity after inferior (posterior)
      wall acute myocardial infarction.
AB  - Tissue Doppler echocardiography is a novel technique that can be used to diagnose
      right ventricular (RV) systolic dysfunction. Until recently, there have been no
      data on the influence of tissue Doppler-derived RV systolic dysfunction on
      exercise capacity after inferior (posterior) myocardial infarction (MI). We
      studied 90 consecutive patients (76% men, mean age 61 +/- 10 years) with first
      inferior ST-segment elevation MI and left ventricular ejection fraction >=45%. RV
      systolic dysfunction was defined as RV systolic myocardial velocity <11.5 cm/s at
      the basal segment of the RV free wall assessed by pulse tissue Doppler. Patients
      were categorized as with or without RV systolic dysfunction (RV systolic
      myocardial velocity 9.34 +/- 1.36 and 13.74 +/- 1.58 cm/s, respectively). A
      cardiopulmonary exercise test was performed before or soon after discharge (day
      14 +/- 10). Patients with RV systolic dysfunction had lower oxygen consumption
      assessed as percent predicted oxygen uptake in liters per minute and milliliters
      per kilogram per minute at their anaerobic threshold (61 +/- 11% vs 69 +/- 17%, p
      = 0.007; 53 +/- 12% vs 61 +/- 19%, p = 0.012, respectively) and at peak exercise
      (71 +/- 12% vs 83 +/- 16%, p = 0.0001; 62 +/- 14% vs 74 +/- 21%, p = 0.002,
      respectively). Multivariate regression analysis revealed that the following
      independent factors negatively influenced exercise capacity: RV systolic
      dysfunction, female gender, age, lower body mass index, current smoking, and
      maximal troponin I concentration. In conclusion, we found decreased exercise
      capacity in patients with systolic RV dysfunction assessed by pulse tissue
      Doppler in patients with inferior (posterior) wall acute MI despite preserved
      left ventricular function.

PMID- 22651880
TI  - Cost-effectiveness of everolimus- versus paclitaxel-eluting stents for patients
      undergoing percutaneous coronary revascularization (from the SPIRIT-IV Trial).
AB  - Although several drug-eluting stents (DESs) have been shown to be economically
      attractive compared to bare-metal stents in patients at moderate to high risk of
      restenosis, little is known about the cost-effectiveness of alternative DES
      designs, especially second-generation DESs. We therefore performed an economic
      substudy alongside the SPIRIT-IV trial, in which 3,687 patients undergoing single
      or multivessel percutaneous coronary intervention were randomized to receive
      second-generation everolimus-eluting stents (EESs; n = 2,458) or first-generation
      paclitaxel-eluting stents (PESs; n = 1,229). Costs through 2 years of follow-up
      were assessed from the perspective of the United States health care system. The
      primary cost-effectiveness end point was the incremental cost-effectiveness ratio
      assessed as cost per quality-adjusted life year gained. Over a 2-year period, use
      of EESs versus PESs led to a trend toward decreased overall repeat
      revascularization procedures (14.2 vs 16.2 per 100 subjects, p = 0.20) driven by
      a significant decrease in the number of target vessel revascularization
      procedures (8.2 vs 11.0 per 100 subjects, p = 0.02) but also a slight increase in
      the number of nontarget vessel revascularization procedures (6.0 vs 5.1 per 100
      subjects, p = 0.37). Follow-up cardiovascular costs were decreased by
      $273/patient in the EES group (95% confidence interval for difference 1,048 less
      to 502 more, p = 0.49). Formal cost-effectiveness analysis based on these results
      demonstrated that the probability that EES was an economically attractive
      strategy (incremental cost-effectiveness ratio <$50,000/quality-adjusted life
      year gained) was 85.7%. These findings demonstrate that in patients undergoing
      percutaneous coronary intervention with DESs, use of EESs is economically
      attractive compared to PESs with improved clinical outcomes and lower overall
      medical care costs at 2 years.

PMID- 22651881
TI  - Cost-effectiveness of rivaroxaban compared to warfarin for stroke prevention in
      atrial fibrillation.
AB  - Rivaroxaban has been found to be noninferior to warfarin for preventing stroke or
      systemic embolism in patients with high-risk atrial fibrillation (AF) and is
      associated with a lower rate of intracranial hemorrhage. To assess the cost
      effectiveness of rivaroxaban compared to adjusted-dose warfarin for the
      prevention of stroke in patients with AF, we built a Markov model using a United
      States payer/Medicare perspective and a lifetime time horizon. The base-case
      analysis assumed a cohort of patients with AF 65 years of age with a congestive
      heart failure, hypertension, age, diabetes, stroke (2 points) score of 3 and no
      contraindications to anticoagulation. Data sources included the Rivaroxaban Once
      daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for
      Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) and
      other studies of anticoagulation. Outcome measurements included costs in 2011
      United States dollars, quality-adjusted life years (QALYs), and incremental cost
      effectiveness ratios (ICERs). Patients with AF treated with rivaroxaban lived an
      average of 10.03 QALYs at a lifetime treatment cost of $94,456. Those receiving
      warfarin lived an average of 9.81 QALYs and incurred costs of $88,544. The ICER
      for rivaroxaban was $27,498 per QALY. These results were most sensitive to
      changes in the hazard decrease of intracranial hemorrhage and stroke with
      rivaroxaban, cost of rivaroxaban, and time horizon. Monte Carlo simulation
      demonstrated rivaroxaban was cost-effective in 80% and 91% of 10,000 iterations
      at willingness-to-pay thresholds of $50,000 and $100,000 per QALY, respectively.
      In conclusion, this Markov model suggests that rivaroxaban therapy may be a cost
      effective alternative to adjusted-dose warfarin for stroke prevention in AF.

PMID- 22651882
TI  - Comparison of circadian rhythm patterns in Tako-tsubo cardiomyopathy versus ST
      segment elevation myocardial infarction.
AB  - Tako-tsubo cardiomyopathy (TTC) is an acute reversible cardiac condition usually
      triggered by stressful events, with a predilection for older women and clinical
      presentation often confused with acute coronary syndrome. Definition of the
      diurnal hourly pattern of TTC events may contribute to understanding the
      pathogenesis of this complex entity. We prospectively enrolled 186 consecutive
      patients with TTC (68 +/- 14 years old, 95% women) and, for comparison, 2,975
      patients with ST-segment elevation myocardial infarction (STEMI) at the
      Minneapolis Heart Institute over the same period. Circadian periodicity was
      analyzed for hourly occurrence of events throughout the day and for days of the
      week and months of the year. Occurrence of TTC showed a nonuniform distribution
      with a distinctive afternoon peak from 12:00 (noon) to 4:00 p.m., comprising 28%
      (n = 52) of all events, and with the nadir at 12 to 4 a.m. (chi-square 25.6, p
      <0.001). Patients with events within the peak were older (73 +/- 13 years) than
      other patients (66 +/- 13 years, p = 0.0025). Events were uniformly distributed
      over days of the week and months (p = 0.2 and 0.47, respectively). In contrast,
      patients with STEMI showed peak occurrence in the early morning hours, 8:00 a.m.
      to 12:00 p.m., comprising 24% of all events (chi-square 248, p <0.001). In
      conclusion, TTC events occurred in a circadian pattern with a peak in the
      afternoon hours, distinctive from the predilection of STEMI for morning hours.
      This timing of TTC events is most consistent with mechanisms underlying stressful
      life situations that usually trigger this condition.

PMID- 22651883
TI  - Downstream testing and subsequent procedures after coronary computed tomographic
      angiography following coronary stenting in patients >=65 years of age.
AB  - Limited data are available on the use of coronary computed tomographic
      angiography (CCTA) in patients who have received percutaneous coronary
      intervention (PCI). To evaluate patterns of cardiac testing including CCTA after
      PCI, we created a retrospective observational dataset linking National
      Cardiovascular Data Registry CathPCI Registry baseline data with longitudinal
      inpatient and outpatient Medicare claims data for patients who received coronary
      stenting from November 1, 2005 through December 31, 2007. In 192,009 patients
      with PCI (median age 74 years), the first test after coronary stenting was CCTA
      for 553 (0.3%), stress testing for 89,900 (46.8%), and coronary angiography for
      22,308 (11.6%); 79,248 (41.3%) had no further testing. Patients referred to CCTA
      first generally had similar or lower baseline risk than those referred for stress
      testing or catheterization first. Compared to patients with stress testing first
      after PCI, patients who underwent CCTA first had higher unadjusted rates of
      subsequent noninvasive testing (10% vs 3%), catheterization (26% vs 15%), and
      revascularization (13% vs 8%) within 90 days of initial testing after PCI (p
      <0.0001 for all comparisons). In conclusion, despite similar or lesser-risk
      profiles, patients initially evaluated with CCTA after PCI had more downstream
      testing and revascularization than patients initially evaluated with stress
      testing. It is unclear whether these differences derive from patient selection,
      performance of CCTA compared to other testing strategies, or the association of
      early adoption of CCTA with distinct patterns of care.

PMID- 22651884
TI  - Triage and clinical management of patients with acute pesticide self-poisoning
      presenting to small rural hospitals.
AB  - Acute pesticide self-poisoning is the single most important cause of fatal self
      harm worldwide, killing at least 250,000 people every year, the vast majority in
      rural Asia. However, for many years the problem was little studied and no
      systematic approach taken to reduce harm and prevent deaths. Eight years ago this
      changed when the World Health Organization (WHO) proposed an inter-sectoral
      public health campaign to improve patient management, prevention, knowledge of
      its epidemiology, and information dissemination. One aim was to improve the
      triage and acute care of pesticide self-poisoned patients presenting to small
      rural hospitals with few resources. To this end, a WHO meeting was held in
      Bangkok at the end of 2007 that developed a protocol for triage and early care
      that was published online. Unfortunately, this approach has not resulted in
      dissemination or uptake and, 4 years later, the guidance has not been widely
      read, critiqued, or used. In this commentary, we describe the basis for the
      guidance that was produced. We hope it will bring the work to a wider clinical
      toxicology audience, to ultimately improve management of pesticide poisoned
      patients, and to encourage clinicians to take part in this important campaign.
      Future attempts to improve clinical care in rural Asia will need to better
      understand and utilise methods for influencing policy makers and clinicians in
      target areas if practice is to be changed.

PMID- 22651885
TI  - Cost of clinical events in health economic evaluations in Germany: a systematic
      review.
AB  - Guidance from the Institute for Quality and Efficiency in Health Care (IQWiG) on
      cost estimation in cost-benefit assessments in Germany acknowledges the need for
      standardization of costing methodology. The objective of this review was to
      assess current methods for deriving clinical event costs in German economic
      evaluations. A systematic literature search of 24 databases (including MEDLINE,
      BIOSIS, the Cochrane Library and Embase) identified articles, published between
      January 2005 and October 2009, which reported cost-effectiveness or cost-utility
      analyses. Studies assessed German patients and evaluated at least one of 11
      predefined clinical events relevant to patients with diabetes mellitus. A total
      of 21 articles, describing 199 clinical cost events, met the inclusion criteria.
      Year of costing and time horizon were available for 194 (97%) and 163 (82%) cost
      events, respectively. Cost components were rarely specified (32 [16%]). Costs
      were generally based on a single literature source (140 [70%]); where multiple
      sources were cited (32 [16%]), data synthesis methodology was not reported. Cost
      ranges for common events, assessed using a Markov model with a cycle length of 12
      months, were: acute myocardial infarction (nine studies), first year, 4,618
      17,556 ?; follow-up years, 1,006-3,647 ?; and stroke (10 studies), first year;
      10,149-24,936 ?; follow-up years, 676-7,337 ?. These results demonstrate that
      costs for individual clinical events vary substantially in German health economic
      evaluations, and that there is a lack of transparency and consistency in the
      methods used to derive them. The validity and comparability of economic
      evaluations would be improved by guidance on standardizing costing methodology
      for individual clinical events.

PMID- 22651887
TI  - Water structure-forming capabilities are temperature shifted for different
      models.
AB  - A large number of water models exist for molecular simulations. They differ in
      the ability to reproduce specific features of real water instead of others, like
      the correct temperature for the density maximum or the diffusion coefficient.
      Past analysis mostly concentrated on ensemble quantities, while few data were
      reported on the different microscopic behavior. Here, we compare seven widely
      used classical water models (SPC, SPC/E, TIP3P, TIP4P, TIP4P-Ew, TIP4P/2005, and
      TIP5P) in terms of their local structure-forming capabilities through hydrogen
      bonds for temperatures ranging from 210 to 350 K by the introduction of a set of
      order parameters taking into account the configuration of up to the second
      solvation shell. We found that all models share the same structural pattern up to
      a temperature shift. When this shift is applied, all models overlap onto a master
      curve. Interestingly, increased stabilization of fully coordinated structures
      extending to at least two solvation shells is found for models that are able to
      reproduce the correct position of the density maximum. Our results provide a self
      consistent atomic-level structural comparison protocol, which can be of help in
      elucidating the influence of different water models on protein structure and
      dynamics.

PMID- 22651886
TI  - Microfluidic electrochemical sensor for on-line monitoring of aerosol oxidative
      activity.
AB  - Particulate matter (PM) air pollution has a significant impact on human morbidity
      and mortality; however, the mechanisms of PM-induced toxicity are poorly defined.
      A leading hypothesis states that airborne PM induces harm by generating reactive
      oxygen species in and around human tissues, leading to oxidative stress. We
      report here a system employing a microfluidic electrochemical sensor coupled
      directly to a particle-into-liquid sampler (PILS) system to measure aerosol
      oxidative activity in an on-line format. The oxidative activity measurement is
      based on the dithiothreitol (DTT) assay, where, after being oxidized by PM, the
      remaining reduced DTT is analyzed by the microfluidic sensor. The sensor consists
      of an array of working, reference, and auxiliary electrodes fabricated in a
      poly(dimethylsiloxane)-based microfluidic device. Cobalt(II) phthalocyanine
      modified carbon paste was used as the working electrode material, allowing
      selective detection of reduced DTT. The electrochemical sensor was validated off
      line against the traditional DTT assay using filter samples taken from urban
      environments and biomass burning events. After off-line characterization, the
      sensor was coupled to a PILS to enable on-line sampling/analysis of aerosol
      oxidative activity. Urban dust and industrial incinerator ash samples were
      aerosolized in an aerosol chamber and analyzed for their oxidative activity. The
      on-line sensor reported DTT consumption rates (oxidative activity) in good
      correlation with aerosol concentration (R(2) from 0.86 to 0.97) with a time
      resolution of approximately 3 min.

PMID- 22651889
TI  - Granulocyte-colony-stimulating factor stimulation of bone marrow mesenchymal
      stromal cells promotes CD34+ cell migration via a matrix metalloproteinase-2
      dependent mechanism.
AB  - Human hematopoietic stem/progenitor cells (HSPCs) can be mobilized into the
      circulation using granulocyte-colony stimulating factor (G-CSF), for graft
      collection in view of hematopoietic transplantation. This process has been
      related to bone marrow (BM) release of serine proteases and of the matrix
      metalloproteinase-9 (MMP-9). Yet, the role of these mediators in HSC egress from
      their niches remains questionable, because they are produced by nonstromal cells
      (mainly neutrophils and monocytes/macrophages) that are not a part of the niche.
      We show here that the G-CSF receptor (G-CSFR) is expressed by human BM
      mesenchymal stromal/stem cells (MSCs), and that G-CSF prestimulation of MSCs
      enhances the in vitro trans-stromal migration of CD34+ cells. Zymography analysis
      indicates that pro-MMP-2 (but not pro-MMP-9) is expressed in MSCs, and that G-CSF
      treatment increases its expression and induces its activation at the cell
      membrane. We further demonstrate that G-CSF-stimulated migration depends on G
      CSFR expression and is mediated by a mechanism that involves MMPs. These results
      suggest a molecular model whereby G-CSF infusion may drive, by the direct action
      on MSCs, HSPC egress from BM niches via synthesis and activation of MMPs. In this
      model, MMP-2 instead of MMP-9 is implicated, which constitutes a major difference
      with mouse mobilization models.

PMID- 22651891
TI  - Preschoolers' sensitivity to speaker action constraints to infer referential
      intent.
AB  - We investigated how preschoolers use their understanding of the actions available
      to a speaker to resolve referential ambiguity. In this study, 58 3- and 4-year
      olds were presented with arrays of eight objects in a toy house and were
      instructed to retrieve various objects from the display. The trials varied in
      terms of whether the speaker's hands were empty or full when she requested an
      object as well as whether the request was ambiguous (i.e., more than one
      potential referent) or unambiguous (i.e., only one potential referent). Results
      demonstrated that both 3- and 4-year-olds were sensitive to speaker action
      constraints and used this information to guide on-line processing (as indexed by
      eye gaze measures) and to make explicit referential decisions.

PMID- 22651890
TI  - Overlapping effector interfaces define the multiple functions of the HIV-1 Nef
      polyproline helix.
AB  - BACKGROUND: HIV-1 Nef is a multifunctional protein required for full
      pathogenicity of the virus. As Nef has no known enzymatic activity, it
      necessarily functions through protein-protein interaction interfaces. A critical
      Nef protein interaction interface is centered on its polyproline segment
      (P69VRPQVPLRP78) which contains the helical SH3 domain binding protein motif,
      PXXPXR. We hypothesized that any Nef-SH3 domain interactions would be lost upon
      mutation of the prolines or arginine of PXXPXR. Further, mutation of the non
      motif "X" residues, (Q73, V74, and L75) would give altered patterns of inhibition
      for different Nef/SH3 domain protein interactions. RESULTS: We found that
      mutations of either of the prolines or the arginine of PXXPXR are defective for
      Nef-Hck binding, Nef/activated PAK2 complex formation and enhancement of virion
      infectivity (EVI). Mutation of the non-motif "X" residues (Q, V and L) gave
      similar patterns of inhibition for Nef/activated PAK2 complex formation and EVI
      which were distinct from the pattern for Hck binding. These results implicate an
      SH3 domain containing protein other than Hck for Nef/activated PAK2 complex
      formation and EVI. We have also mutated Nef residues at the N-and C-terminal ends
      of the polyproline segment to explore interactions outside of PXXPXR. We
      discovered a new locus GFP/F (G67, F68, P69 and F90) that is required for
      Nef/activated PAK2 complex formation and EVI.MHC Class I (MHCI) downregulation
      was only partially inhibited by mutating the PXXPXR motif residues, but was fully
      inhibited by mutating the C-terminal P78. Further, we observed that MHCI
      downregulation strictly requires G67 and F68. Our mutational analysis confirms
      the recently reported structure of the complex between Nef, AP-1 MU1 and the
      cytoplasmic tail of MHCI, but does not support involvement of an SH3 domain
      protein in MHCI downregulation. CONCLUSION: Nef has evolved to be dependent on
      interactions with multiple SH3 domain proteins. To the N- and C- terminal sides
      of the polyproline helix are multifunctional protein interaction sites. The
      polyproline segment is also adapted to downregulate MHCI with a non-canonical
      binding surface. Our results demonstrate that Nef polyproline helix is highly
      adapted to directly interact with multiple host cell proteins.

PMID- 22651892
TI  - The effects of coaching on the verbal and nonverbal medical symptom validity
      tests.
AB  - Evaluation of resistance to coaching is an important step in the validation of
      symptom validity tests (SVTs) for clinical use in neuropsychological evaluations.
      In the present study coaching effects were evaluated for two recently developed
      SVTs, the Medical Symptom Validity Test (MSVT) and Nonverbal Medical Symptom
      Validity Test (NVMSVT) as compared with a well-validated existing SVT, the Test
      of Memory Malingering (TOMM). This study used a simulation design that included
      103 healthy younger study volunteers who were randomly assigned into one of four
      conditions: Symptom Coaching, Test Coaching, Combined Coaching, or Best Effort
      Control. Specificity for all SVTs was excellent (96-100%). Test Coaching, either
      alone or combined with Symptom Coaching, was more effective than Symptom Coaching
      alone in producing raw scores suggestive of "better" effort for all SVTs.
      However, there were only modest declines in the obtained sensitivity, which
      remained above 80% for all SVTs. These results provide empirical support for the
      classification accuracy of the MSVT and NVMSVT, even when challenged with
      combined coaching interventions. However, further validation using known-groups
      designs and clinical samples is needed.

PMID- 22651893
TI  - Guideline for the diagnosis and management of myelofibrosis.
AB  - The guideline group regarding the diagnosis and management of myelofibrosis was
      selected to be representative of UK-based medical experts, together with a
      contribution from a single expert from the USA. MEDLINE and EMBASE were searched
      systematically for publications in English from 1966 until August 2011 using a
      variety of key words. The writing group produced the draft guideline, which was
      subsequently revised by consensus of the members of the General Haematology and
      Haemato-oncology Task Forces of the British Committee for Standards in
      Haematology (BCSH). The guideline was then reviewed by a sounding board of UK
      haematologists, the BCSH and the British Society for Haematology Committee and
      comments incorporated where appropriate. The criteria used to state levels and
      grades of evidence are as outlined in the Procedure for Guidelines commissioned
      by the BCSH; the 'GRADE' system was used to score strength and quality of
      evidence. The objective of this guideline is to provide healthcare professionals
      with clear guidance on the investigation and management of primary myelofibrosis,
      as well as post-polycythaemic myelofibrosis (post-PV MF) and post-thrombocythemic
      myelofibrosis (post-ET MF) in both adult and paediatric patients.

PMID- 22651894
TI  - Editorial: Proteostasis-imbalance and pathogenesis of chronic obstructive lung
      diseases.

PMID- 22651895
TI  - Universal rapid screening for methicillin-resistant Staphylococcus aureus in the
      intensive care units in a large community hospital.
AB  - BACKGROUND: Health care-associated methicillin-resistant Staphylococcus aureus
      (HA-MRSA) infections constitute a significant risk for hospitalized patients.
      This study evaluates the costs and effects of comprehensive and state-mandated
      MRSA screening for intensive care unit (ICU) patients and subsequent contact
      precautions on the rate of HA-MRSA. METHODS: A pre- and postimplementation study
      was conducted in a 24-bed medical intensive care unit (MICU) and a 15-bed
      surgical intensive care unit (SICU) at an acute care 536-bed community hospital.
      This study used computerized records for all patients admitted to ICUs. Costs
      were estimated from financial records. RESULTS: HA-MRSA infection rates did not
      decline after implementation of ICU screening. Regression analysis demonstrated
      that patients admitted from skilled nursing facilities, assisted living, and
      similar facilities were 12 times more likely to screen positive for MRSA as
      compared with patients admitted from home. The costs to identify each MRSA
      positive patient were $1,650 and $953 for comprehensive and state-mandated
      periods, respectively. CONCLUSION: In low prevalence hospitals without MRSA
      outbreaks, it is recommended that MRSA screening be conducted on patients
      admitted from skilled nursing and similar facilities because they are most likely
      to be colonized with MRSA. Results do not support mandates to conduct screening
      on all patients admitted to critical care units.

PMID- 22651896
TI  - Functional quality of life following open valve surgery in high-risk
      octogenarians.
AB  - AIM: The aim of this study was to determine the midterm functional quality of
      life in octogenarians after open valvular surgery. METHODS: One hundred and
      eighty-five consecutive patients above age 80 had valvular surgery with or
      without coronary artery bypass grafting (CABG). Using the Karnofsky Performance
      score and Barthel Index, patients were evaluated for functional autonomy, living
      disposition, and leisure activity by a single telephone interview. Subgroup
      analysis was performed on the 49 cases of isolated aortic valve replacement
      (AVR). RESULTS: Mean age of octogenarians undergoing valvular surgery was 82.7
      years (range 80 to 92 years). Actuarial survival at one and three years was 71%
      and 59%, respectively, for the entire group, compared to 84% and 71%,
      respectively, for isolated AVRs. After a mean follow-up of 38 months there were
      110 survivors (59.5%). Among survivors, 66% were autonomous, 26% semiautonomous,
      and 8% deemed dependent. Seventy-two percent were living at home, 19% in a
      residence, and 9% in a supervised nursing facility. Over 90% of patients pursued
      leisure activities in the social, cognitive, and physical domains. CONCLUSIONS:
      Valvular surgery in high-risk octogenarians, can be performed with acceptable
      mortality rates, and provide patients with functional autonomy and an excellent
      quality of life.

PMID- 22651898
TI  - Correlation or causation? Income inequality and infant mortality in fixed effects
      models in the period 1960-2008 in 34 OECD countries.
AB  - Income inequality is strongly associated with infant mortality across countries,
      but whether this association is causal has not been established. In their
      commentary in this issue of Social Science & Medicine, Regidor et al. (2012)
      argue that this association has disappeared in recent years, and question the
      premise of a causal link. This paper empirically tests the impact of income
      inequality on infant mortality in a fixed effects model that exploits the
      evolution of income inequality over a 38-year period, controlling for all time
      invariant differences across countries. Data came from the Standardized World
      Income Inequality Database, containing yearly estimates for the period 1960-2008
      in 34 countries member of the Organization for Economic Co-operation and
      Development (OECD), linked to infant mortality data from the OECD Health
      database. Infant mortality was modelled as a function of income inequality in a
      country and year fixed effects model, incorporating controls for changing
      economic and labour conditions. In a model without country fixed effects, a one
      point increase in the Gini coefficient was associated with a 7% increase in the
      infant mortality rate (Rate ratio[RR] = 1.07, 95% Confidence Interval [CI] 1.04,
      1.09). Controlling for differences across countries in a country fixed effects
      model, however, income inequality was no longer associated with infant mortality
      (RR = 1.00, 0.98, 1.01). Similar results were obtained when using lagged values
      of income inequality for up to 15 years, and in models that controlled for
      changing labour and economic conditions. Findings suggest that in the short-run,
      changes in income inequality are not associated with changes in infant mortality.
      A possible interpretation of the discrepancy between cross-country correlations
      and fixed effects models is that social policies that reduce infant mortality
      cluster in countries with low income inequality, but their effects do not operate
      via income. Findings highlight the need to examine the impact of more specific
      social policies on infant mortality.

PMID- 22651897
TI  - Sleep budgets in a globalizing world: biocultural interactions influence sleep
      sufficiency among Egyptian families.
AB  - Declines in self-reported sleep quotas with globalizing lifestyle changes have
      focused attention on their possible role in rising global health problems such as
      obesity or depression. Cultural factors that act across the life course and
      support sleep sufficiency have received scant attention, nor have the potential
      interactions of cultural and biological factors in age-related changes in sleep
      behavior been systematically investigated. This study examines the effects of
      cultural norms for napping and sleeping arrangements along with sleep schedules,
      age, and gender on sleep budgets among Egyptian households. Data were collected
      in 2000 from 16 households with 78 members aged 3-56 years at two sites in Egypt
      (Cairo and an agrarian village). Each participant provided one week of continuous
      activity records and details of each sleep event. Records showed that nighttime
      sleep onsets were late and highly variable. Napping was common and, along with
      wake time flexibility, played a key role in maintaining sleep sufficiency
      throughout the life course into later middle age. Cosleeping was prevalent and
      exhibited contrasting associations with reduced duration and sufficiency of both
      nocturnal and total sleep, and with earlier, more regular, and less disrupted
      sleep. Daily sleep quotas met published guidelines and showed age-related changes
      similar to existing reports, but differed in how they were achieved. Cultural
      norms organizing sleep practices by age and gender appear to tap their intrinsic
      biological properties as well. Moreover, flexibility in how sleep was achieved
      contributed to sleep sufficiency. The findings suggest how biocultural dynamics
      can play key roles in sleep patterns that sustain favorable sleep quotas from
      infancy onwards in populations pursuing globalizing contemporary lifestyles.

PMID- 22651899
TI  - Dengue infections in non-immune travellers to Thailand.
AB  - Dengue is the most frequent arboviral disease and is expanding geographically.
      Dengue is also increasingly being reported in travellers, in particular in
      travellers to Thailand. However, data to quantify the risk of travellers
      acquiring dengue when travelling to Thailand are lacking. Using mathematical
      modelling, we set out to estimate the risk of non-immune persons acquiring dengue
      when travelling to Thailand. The model is deterministic with stochastic
      parameters and assumes a Poisson distribution for the mosquitoes' biting rate and
      a Gamma distribution for the probability of acquiring dengue from an infected
      mosquito. From the force of infection we calculated the risk of dengue
      acquisition for travellers to Thailand arriving in a typical year (averaged over
      a 17-year period) in the high season of transmission. A traveller arriving in the
      high season of transmission and remaining for 7 days has a risk of acquiring
      dengue of 0.2% (95% CI 0.16-0.23), whereas the risk for travel of 15 and 30 days'
      duration is 0.46% (95% CI 0.41-0.50) and 0.81% (95% CI 0.76-0.87), respectively.
      Our data highlight that the risk of non-immune travellers acquiring dengue in
      Thailand is substantial. The incidence of 0.81% after a 1-month stay is similar
      to that reported in prospective seroconversion studies in Israeli travellers to
      Thailand, highlighting that our models are consistent with actual data. Risk
      estimates based on mathematical modelling offer more detailed information
      depending on various travel scenarios, and will help the travel medicine provider
      give better evidence-based advice for travellers to dengue-endemic countries.

PMID- 22651900
TI  - Assessment of network perturbation amplitudes by applying high-throughput data to
      causal biological networks.
AB  - BACKGROUND: High-throughput measurement technologies produce data sets that have
      the potential to elucidate the biological impact of disease, drug treatment, and
      environmental agents on humans. The scientific community faces an ongoing
      challenge in the analysis of these rich data sources to more accurately
      characterize biological processes that have been perturbed at the mechanistic
      level. Here, a new approach is built on previous methodologies in which high
      throughput data was interpreted using prior biological knowledge of cause and
      effect relationships. These relationships are structured into network models that
      describe specific biological processes, such as inflammatory signaling or cell
      cycle progression. This enables quantitative assessment of network perturbation
      in response to a given stimulus. RESULTS: Four complementary methods were devised
      to quantify treatment-induced activity changes in processes described by network
      models. In addition, companion statistics were developed to qualify significance
      and specificity of the results. This approach is called Network Perturbation
      Amplitude (NPA) scoring because the amplitudes of treatment-induced perturbations
      are computed for biological network models. The NPA methods were tested on two
      transcriptomic data sets: normal human bronchial epithelial (NHBE) cells treated
      with the pro-inflammatory signaling mediator TNFalpha, and HCT116 colon cancer
      cells treated with the CDK cell cycle inhibitor R547. Each data set was scored
      against network models representing different aspects of inflammatory signaling
      and cell cycle progression, and these scores were compared with independent
      measures of pathway activity in NHBE cells to verify the approach. The NPA
      scoring method successfully quantified the amplitude of TNFalpha-induced
      perturbation for each network model when compared against NF-kappaB nuclear
      localization and cell number. In addition, the degree and specificity to which
      CDK-inhibition affected cell cycle and inflammatory signaling were meaningfully
      determined. CONCLUSIONS: The NPA scoring method leverages high-throughput
      measurements and a priori literature-derived knowledge in the form of network
      models to characterize the activity change for a broad collection of biological
      processes at high-resolution. Applications of this framework include comparative
      assessment of the biological impact caused by environmental factors, toxic
      substances, or drug treatments.

PMID- 22651902
TI  - Treatment-related mortality with vascular endothelial growth factor receptor
      tyrosine kinase inhibitor therapy in patients with advanced solid tumors: a meta
      analysis.
AB  - BACKGROUND: Several vascular endothelial growth factor receptor tyrosine kinase
      inhibitors (VEGFR TKI) are now approved by regulatory agencies and are important
      in the treatment of solid tumor malignancies. The risk of fatal adverse events
      (FAEs) with these agents is not well characterized. METHODS: PubMed was searched
      for articles published from 2001 until 2011. Eligible studies included
      prospective randomized trials evaluating sunitinib, sorafenib, pazopanib, and
      vandetanib in patients with all malignancies. Thirteen eligible randomized
      controlled trials were included in a meta-analysis and the number of FAEs
      (defined by the National Cancer Institute's Common Terminology Criteria for
      Adverse Events (CTCAE) criteria) was extracted and study quality was calculated.
      Incidence rates and relative risks were calculated for all thirteen studies as
      well as for the subset of patients with renal cell carcinoma. RESULTS: Analysis
      of the 5164 patients across 13 RCTs revealed that the relative risk was 1.64 (95%
      CI, 1.16, 2.32; P=0.01; incidence 2.26% vs. 1.26%) for the association of a VEGFR
      TKI with FAEs using a random-effects model. All exploratory subgroup analyses
      indicated a trend toward an increase risk of FAEs with VEGFR TKI treatment,
      though the subgroup analyses reached statistical significance for renal carcinoma
      studies, studies utilizing placebo as the control arm, and studies evaluating
      sorafenib. INTERPRETATION: This analysis suggests that VEGFR TKIs are associated
      with a significant increase in the risk of FAEs in patients with advanced solid
      tumors.

PMID- 22651903
TI  - Interleukin-6 signaling pathway in targeted therapy for cancer.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine which plays an important role
      in a wide range of biologic activities in different types of cell including tumor
      cells. IL-6 is involved in the host immune defense mechanism as well as the
      modulation of growth and differentiation in various malignancies. These effects
      are mediated by several signaling pathways, in particular the signal transducer
      and transcription activator 3 (Stat3). There exists abundant evidence
      demonstrating that deregulated overexpression of IL-6 was associated with tumor
      progression through inhibition of cancer cell apoptosis, stimulation of
      angiogenesis, and drug resistance. Clinical studies have revealed that increased
      serum IL-6 concentrations in patients are associated with advanced tumor stages
      of various cancers (e.g., multiple myeloma, non-small cell lung carcinoma,
      colorectal cancer, renal cell carcinoma, prostate cancer, breast cancer and
      ovarian cancer) and short survival in patients. Therefore, blocking IL-6
      signaling is a potential therapeutic strategy for cancer (i.e., anti-IL-6
      therapy) characterized by pathological IL-6 overproduction. Preliminary clinical
      evidence has shown that antibody targeted IL-6 therapy was well tolerated in
      cancer patients. In this review, we detail the progress of the current
      understanding of IL-6 signaling pathway in cancer as well as an antibody targeted
      IL-6 therapy for human cancer.

PMID- 22651901
TI  - Inborn errors of human STAT1: allelic heterogeneity governs the diversity of
      immunological and infectious phenotypes.
AB  - The genetic dissection of various human infectious diseases has led to the
      definition of inborn errors of human STAT1 immunity of four types, including (i)
      autosomal recessive (AR) complete STAT1 deficiency, (ii) AR partial STAT1
      deficiency, (iii) autosomal dominant (AD) STAT1 deficiency, and (iv) AD gain of
      STAT1 activity. The two types of AR STAT1 defect give rise to a broad infectious
      phenotype with susceptibility to intramacrophagic bacteria (mostly mycobacteria)
      and viruses (herpes viruses at least), due principally to the impairment of IFN
      gamma-mediated and IFN-alpha/beta-mediated immunity, respectively. Clinical
      outcome depends on the extent to which the STAT1 defect decreases responsiveness
      to these cytokines. AD STAT1 deficiency selectively predisposes individuals to
      mycobacterial disease, owing to the impairment of IFN-gamma-mediated immunity, as
      IFN-alpha/beta-mediated immunity is maintained. Finally, AD gain of STAT1
      activity is associated with autoimmunity, probably owing to an enhancement of IFN
      alpha/beta-mediated immunity. More surprisingly, it is also associated with
      chronic mucocutaneous candidiasis, through as yet undetermined mechanisms
      involving an inhibition of the development of IL-17-producing T cells. Thus,
      germline mutations in human STAT1 define four distinct clinical disorders.
      Various combinations of viral, mycobacterial and fungal infections are therefore
      allelic at the human STAT1 locus. These experiments of Nature neatly highlight
      the clinical and immunological impact of the human genetic dissection of
      infectious phenotypes.

PMID- 22651904
TI  - The role of the tumour inflammatory cell infiltrate in predicting recurrence and
      survival in patients with primary operable breast cancer.
AB  - Although the first studies highlighting the importance of the tumour inflammatory
      cell infiltrate were reported more than 80 years ago, the prognostic value of
      this response in breast cancer is still controversial. With the realisation of
      the importance of the inflammatory response in determining tumour progression
      there has been renewed interest in establishing the relationship between the
      type, density and location of inflammatory cell infiltrate and survival in
      patients with primary operable breast cancer. The aim was to undertake a
      systematic review of the literature examining the evidence for the role of the
      tumour inflammatory cell infiltrate in predicting recurrence and survival in
      patients with primary operable breast cancer. A systematic review of published
      papers up to September 2011 was undertaken according to a pre-defined protocol
      (Fig. 1). A total of 66 independent studies (34,086 patients) were identified. It
      can be concluded from the review that despite the large number of studies and
      considerable effort over an extended period, the relationship between different
      aspects of tumour inflammatory cell infiltrate and outcome in primary operable
      breast cancer remains unclear. This is in large part due to the absence of
      methodological validation, underpowered studies (small sample size and sample
      subtype heterogeneity, insufficient follow-up) and the absence of validation
      datasets. Therefore, although there are tantalising examples of the potential of
      the tumour inflammatory cell infiltrate to improve risk stratification patients
      with operable breast cancer (personalised care), this has not yet been realised.
      Future studies with standardised methodology, large and homogenous groups,
      sufficient follow-up and validation datasets should be undertaken to unlock the
      potential of the tumour inflammatory infiltrate to predict outcome in patients
      with primary operable breast cancer.

PMID- 22651905
TI  - Application of ADC measurement in characterization of renal cell carcinomas with
      different pathological types and grades by 3.0T diffusion-weighted MRI.
AB  - PURPOSE: To test the feasibility of apparent diffusion coefficient (ADC) value
      obtained with 3.0 T diffusion-weighted imaging (DWI) in the characterization of
      renal cell carcinomas (RCC) with different pathological subtypes and grades.
      MATERIALS AND METHODS: A total of 137 patients who were diagnosed with RCC and
      underwent DWI were included in this study. The diagnosis was confirmed by
      pathological examination of surgical specimens. Images of DWI were obtained with
      b values of 0 and 800 s/mm2. The ADC values in the solid area of tumors and in
      the corresponding regions of contralateral normal renal parenchyma were measured
      and analyzed statistically. RESULTS: The mean ADC value was significantly lower
      in RCC (1.381+/-0.444*10(-3) mm2/s) than in normal renal parenchyma (2.232+/
      0.221*10(-3) mm2/s) (P<0.001). The ADC value was also statistically different
      between clear cell RCC (CCRCC) and non-CCRCC, and between different grades of
      CCRCC except grade I vs II and grade III vs IV. CONCLUSION: ADC measurement on
      3.0 T DWI provides useful information in diagnostic work-up of RCC in terms of
      differentiation of RCC and normal renal parenchyma, and characterization of RCC
      with different pathological subtypes and grades.

PMID- 22651906
TI  - A photo Lewis acid generator (PhLAG): controlled photorelease of B(C6F5)3.
AB  - A molecule that releases the strong organometallic Lewis acid B(C(6)F(5))(3) upon
      irradiation with 254 nm light has been developed. This photo Lewis acid generator
      (PhLAG) now enables the photocontrolled initiation of several reactions catalyzed
      by this important Lewis acid. Herein is described the synthesis of the
      triphenylsulfonium salt of a carbamato borate based on a carbazole function, its
      establishment as a PhLAG, and the application of the photorelease of
      B(C(6)F(5))(3) to the fabrication of thin films of a polysiloxane material.

PMID- 22651907
TI  - Dissolution and microstructural transformation of ZnO nanoparticles under the
      influence of phosphate.
AB  - The toxicity and fate of nanoparticles (NPs) have been reported to be highly
      dependent on the chemistry of the medium, and the effects of phosphate have
      tended to be ignored despite the wide existence of phosphate contamination in
      aqueous environments. In the present study the influence of phosphate on the
      dissolution and microstructural transformation of ZnO NPs was investigated.
      Phosphate at a low concentration rapidly and substantially reduced the release of
      Zn(2+) into aqueous solution. Synchrotron X-ray absorption spectroscopy and X-ray
      diffraction analysis reveal that interaction between ZnO NPs and phosphate
      induced the transformation of ZnO into zinc phosphate. Transmission electronic
      microscopy observation shows that the morphology of the particles changed from
      structurally uniform nanosized spherical to anomalous and porous material
      containing mixed amorphous and crystalline phases of ZnO and zinc phosphate in
      the presence of phosphate. To our knowledge, this is the first study in which the
      detailed process of phosphate-induced speciation and microstructural
      transformation of ZnO NPs has been analyzed. In view of the wide existence of
      phosphate contamination in water and its strong metal-complexation capability,
      phosphate-induced transformations may play an important role in the behaviors,
      fate, and toxicity of many other metal-based nanomaterials in the environment.

PMID- 22651908
TI  - Neighborhood disorder and screen time among 10-16 year old Canadian youth: a
      cross-sectional study.
AB  - BACKGROUND: Screen time activities (e.g., television, computers, video games)
      have been linked to several negative health outcomes among young people. In order
      to develop evidence-based interventions to reduce screen time, the factors that
      influence the behavior need to be better understood. High neighborhood disorder,
      which may encourage young people to stay indoors where screen time activities are
      readily available, is one potential factor to consider. METHODS: Results are
      based on 15,917 youth in grades 6-10 (aged 10-16 years old) who participated in
      the Canadian 2009/10 Health Behaviour in School-aged Children Survey (HBSC).
      Total hours per week of television, video games, and computer use were reported
      by the participating students in the HBSC student questionnaire. Ten items of
      neighborhood disorder including safety, neighbors taking advantage,
      drugs/drinking in public, ethnic tensions, gangs, crime, conditions of
      buildings/grounds, abandoned buildings, litter, and graffiti were measured using
      the HBSC student questionnaire, the HBSC administrator questionnaire, and
      Geographic Information Systems. Based upon these 10 items, social and physical
      neighborhood disorder variables were derived using principal component analysis.
      Multivariate multilevel logistic regression analyses were used to examine the
      relationship between social and physical neighborhood disorder and individual
      screen time variables. RESULTS: High (top quartile) social neighborhood disorder
      was associated with approximately 35-45% increased risk of high (top quartile)
      television, computer, and video game use. Physical neighborhood disorder was not
      associated with screen time activities after adjusting for social neighborhood
      disorder. However, high social and physical neighborhood disorder combined was
      associated with approximately 40-60% increased likelihood of high television,
      computer, and video game use. CONCLUSION: High neighborhood disorder is one
      environmental factor that may be important to consider for future public health
      interventions and strategies aiming to reduce screen time among youth.

PMID- 22651909
TI  - The management of traumatic isolated inferior rectus rupture.
AB  - Traumatic inferior rectus rupture is a rare cause of diplopia following blunt
      trauma in the absence of blowout fracture. We report the case of a heavy goods
      vehicle driver, aged 42 years, with isolated rupture of the inferior rectus
      following blunt ocular trauma. The technique of repair, using a Hummelsheim-type
      procedure, is described. Good alignment was achieved at 1 month following
      surgery, with an excellent field of binocular vision. Other than vertical
      diplopia on extreme upgaze, the patient was asymptomatic and remained so 15
      months following surgery. He was able to continue his job without any significant
      visual concerns. The surgical outcome was better than that described in previous
      reports of inferior rectus rupture. We feel that a Hummelsheim-type procedure is
      a useful option in the management of inferior rectus rupture.

PMID- 22651910
TI  - Casting a shadow on liver X receptor-mediated atheroprotection: is LXRbeta to
      blame?

PMID- 22651912
TI  - The first Tufts University seminar on the obesity epidemic: science and food
      economics.

PMID- 22651911
TI  - Effects of increased systemic inflammation and central obesity on arterial
      stiffness in patients with nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is associated with increasing arterial
      stiffness. We studied the effects of inflammation on different measurements of
      arterial stiffness in NAFLD. We recruited 80 patients with NAFLD and 40 control
      subjects. Both compliance index (CI) and stiffness index (SI) were measured.
      Patients with NAFLD had significantly lower CI (3.8 +/- 2.1 vs 4.9 +/- 2.9 units;
      P < .05) and higher SI (8.5 +/- 2.4 vs 7.1 +/- 1.5 m/s; P < .05) than the
      controls. Patients with NAFLD were further divided into 2 groups according to the
      median level of high-sensitivity C-reactive protein (hs-CRP). The CI was
      significantly lower in patients with NAFLD with high hs-CRP than in those with
      low hs-CRP (3.2 +/- 1.7 vs 4.4 +/- 2.5 units; P < .05); however, SI was not
      statistically different. We further found that waist circumference (odds ratio,
      1.06; 95% confidence interval, 1.01-1.13; P < .05) was the only independent
      factor that predicted low CI (<median value) in patients with NAFLD. Central
      obesity was an important determinant both for increased arterial stiffness and hs
      CRP in Patients with NAFLD.

PMID- 22651913
TI  - TGF-beta signaling in development and disease.

PMID- 22651914
TI  - Structural studies of the TGF-betas and their receptors - insights into evolution
      of the TGF-beta superfamily.
AB  - TGF-betas are small secreted signaling proteins that function as vital regulators
      of cellular growth and differentiation. They signal through a single pair of
      receptors, known as TbetaR-I and TbetaR-II, and are among the most recently
      evolved members of the signaling superfamily to which they belong. This review
      provides an overview of the TGF-beta, BMP, and activin receptor complexes that
      have been determined over the past several years. These structures underscore the
      shared ancestry of the TGF-betas with the BMPs and activins, but also provide
      insight as to how the TGF-betas diverged from the BMPs and activins to bind and
      assemble their receptors in a distinct manner. These distinctive modes of
      receptor binding engender the TGF-betas with high specificity for their receptors
      and allow them to fulfill their essential functions in vivo without interference
      from the many other proteins of the superfamily.

PMID- 22651915
TI  - Identifying newly acquired cases of hepatitis C using surveillance: a literature
      review.
AB  - Surveillance of newly acquired hepatitis C virus (HCV) infection is crucial for
      understanding the epidemiology of HCV and informing public health practice.
      However, monitoring such infections via surveillance systems is challenging
      because they are commonly asymptomatic. A literature review was conducted to
      identify methodologies used by HCV surveillance systems to identify newly
      acquired infections; relevant surveillance systems in 15 countries were
      identified. Surveillance systems used three main strategies to identify newly
      acquired infections: (1) asking physicians to classify cases; (2) identifying
      symptomatic cases or cases with elevated alanine aminotransferases; and (3)
      identifying cases with documented evidence of anti-HCV antibody seroconversion
      within a specific time-frame. Case-ascertainment methods varied with greater
      completeness of data in enhanced compared to passive surveillance systems.
      Automated systems that extract and link testing data from multiple laboratory and
      clinic databases may provide an opportunity for collecting testing histories for
      individuals that is less resource intensive than enhanced surveillance.

PMID- 22651916
TI  - HLA-G polymorphisms and soluble HLA-G protein levels in women with recurrent
      pregnancy loss from Basrah province in Iraq.
AB  - HLA-G is a nonclassical, class I major histocompatibility complex (MHC) gene that
      exhibits immunomodulatory properties and likely plays a role in the maintenance
      of successful pregnancy. In this study, we investigated the role of HLA-G
      polymorphisms on risk for recurrent pregnancy loss (RPL) and on circulating
      levels of soluble (s)HLA-G in Iraqi women. DNA and plasma were obtained from
      blood samples collected at 9-12 weeks gestation from 50 women with RPL and 50
      healthy pregnant women in Basrah province, Iraq. As measured by ELISA, median
      sHLA-G levels were significantly lower in the RPL cases compared to healthy
      controls (21.4 vs. 38.8 U/ml, respectively; P=0.025), and decreased with
      increasing maternal age (P=0.0051). However, HLA-G allele and haplotype
      frequencies did not differ significantly between cases and controls (P values
      >=0.12 for all tests). In contrast, homozygosity for the C allele (CC) at a tri
      allelic promoter polymorphism, -725C/G/T, was associated with lower
      concentrations of sHLA-G compared to the CG or CT genotypes (median levels 21.1
      vs. 40.1 vs. 42.6 U/ml, respectively; P=0.0089). These results demonstrate that
      HLA-G genotype influences circulating sHLA-G levels during pregnancy but is not
      significantly associated with risk of RPL.

PMID- 22651917
TI  - High glucose concentration in T1D patients modulates apoptotic protein
      expression: down regulation of BAX and FAS and up regulation of XIAP.
AB  - Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by a
      progressive destruction of pancreatic beta cells. It has been reported that
      patients with autoimmune diseases exhibit decreased expression of caspase 3 and
      other pro-apoptotic markers in peripheral blood mononuclear cells (PBMC). AIM: To
      estimate the expression of apoptosis markers in PBMC from T1D patients cultured
      with high glucose concentration. RESULTS: At 11 mM of glucose, the pro-apoptotic
      gene fas showed a 7-fold decreased expression in the T1D group compared to
      controls, while bax showed a 50-fold decreased expression (medians 0.14 and 0.02,
      respectively, considering patients as 1). At 44 mM of glucose, there is a
      decreased expression of the same genes, but less abrupt (medians 0.75 and 0.47).
      Only the anti-apoptotic gene xiap showed a 2-fold increased expression at 11 mM
      of glucose (median 2.3). Regarding the clinical history, no relationships were
      observed with age of diagnosis, ketoacidosis, glucose at debut or GAD-65 and IA-2
      titles. CONCLUSION: We can conclude that the apoptotic mechanisms in PBMC of T1D
      patients under high glucose conditions are altered, and this is proved by the
      decreased expression of the pro-apoptotic genes fas and bax and by the increased
      expression of the anti-apoptotic gene xiap.

PMID- 22651918
TI  - Spontaneous atraumatic fracture of a cervical vertebra in tuberculosis: a case
      report.
AB  - INTRODUCTION: Spontaneous pathological fractures of the cervical spine due to
      tuberculosis are rare. But with escalating incidences of atypical presentations
      of tubercular disease, clinicians should exercise a high index of suspicion for
      early diagnosis of such cases. CASE PRESENTATION: We present a case of a 50-year
      old Hindu man from northern India, who complained of pain and stiffness in his
      neck. His radiographs showed a fracture in his second cervical vertebral body.
      But further investigations raised the suspicion of an infective pathology, which
      was corroborated by magnetic resonance imaging and fine needle aspiration
      cytology. His symptoms improved and the fracture healed following antitubercular
      chemotherapy and immobilization. CONCLUSION: In endemic regions like India,
      clinicians should be on the lookout for atypical presentations of tuberculosis.
      Any suspicious lesion should be evaluated with care for clinical, radiological
      and laboratory evidences of the infection. The affected spine should be protected
      and appropriate chemotherapy should be instituted at the earliest opportunity.

PMID- 22651919
TI  - Expression and purification of the antimicrobial peptide cecropin AD by fusion
      with cationic elastin-like polypeptides.
AB  - Cationic elastin-like polypeptides (CELP) are thermally responsive polypeptides
      that undergo an inverse temperature phase transition, and the recombinant CELP
      fusion proteins may be purified by inverse transition cycling (ITC). To obtain
      high-purity antimicrobial peptide cecropin AD (CAD), CELP was placed at the N
      terminus of CAD and the expression vector pET28a-CELP-CAD was constructed. The
      expression vector was then transformed into Escherichia coli BL21 (DE3) to
      express the recombinant protein. After three rounds of ITC, enterokinase
      digestion and another hot spin, 1.2mg recombinant CAD was purified from 100ml
      culture medium. The antimicrobial test indicated that the high-purity CAD had
      strong antimicrobial activity against E. coli and Staphylococcus aureus.

PMID- 22651920
TI  - Contextual representations increase analogue traumatic intrusions: evidence
      against a dual-representation account of peri-traumatic processing.
AB  - BACKGROUND AND OBJECTIVES: Information processing accounts of post-traumatic
      stress disorder (PTSD) state that intrusive memories emerge due to a lack of
      integration between perceptual and contextual trauma representations in
      autobiographical memory. This hypothesis was tested experimentally using an
      analogue trauma paradigm in which participants viewed an aversive film designed
      to elicit involuntary recollections. METHOD: Participants viewed scenes from the
      film either paired with contextual information or with the contextual information
      omitted. After viewing the film participants were asked to record for one week
      any involuntary intrusions for the film using a provided intrusions diary.
      RESULTS: The results revealed a significant increase in analogue intrusions for
      the film when viewed with contextual information in comparison to when the film
      was viewed with the contextual information omitted. In contrast there was no
      effect of contextual information on valence ratings or voluntary memory for the
      film, or on the reported vividness and emotionality of the intrusions.
      LIMITATIONS: The analogue trauma paradigm may have failed to reproduce the effect
      of extreme stress on encoding that is postulated to occur during PTSD.
      CONCLUSIONS: The findings have potential implications for trauma intervention as
      they suggest that the contextual understanding of a scene during encoding can be
      integral to the subsequent occurrence of traumatic intrusions. The pattern of
      results found in the study are inconsistent with dual-representation accounts of
      intrusive memory formation, and instead provide new evidence that contextual
      representations play a casual role in increasing the frequency of involuntary
      intrusions for traumatic material.

PMID- 22651921
TI  - Behavior as information: "If I avoid, then there must be a danger".
AB  - BACKGROUND AND OBJECTIVES: Cognitive models of anxiety disorders view safety
      seeking behaviors (i.e., avoidance, washing, etc.) as playing a crucial role in
      the maintenance of irrational fear. An explanation of how these behaviors may
      contribute to the maintenance of unrealistic beliefs is that patients use their
      safety behaviors as a source of information about the situation (behavior as
      information): the behavior is clear evidence of the danger. This study
      investigates whether, relative to non-clinical control participants, anxious
      participants actually infer danger on the basis of their safety behaviors, rather
      than on the basis of objective information. METHODS: Three groups of individuals
      affected by anxiety disorders (31 obsessive-compulsive participants, 22 panic
      participants, and 17 participants with social phobia) and a group (31) of non
      clinical controls rated the danger perceived in scripts in which information
      about objective safety vs. objective danger, and safety behavior vs. no-safety
      behavior were systematically varied. RESULTS: As expected, anxious participants
      were influenced by both objective danger information and safety behavior
      information, while the non-clinical controls were mainly influenced by objective
      danger but not by safety behavior information. The effect was disturbance
      specific, but only for individuals with social phobia and obsessive-compulsive
      disorder. CONCLUSIONS: The tendency to infer danger on the basis of the use of
      safety behavior may play a role in the development and maintenance of anxiety
      disorders.

PMID- 22651922
TI  - An analysis of matching cognitive-behavior therapy techniques to learning styles.
AB  - BACKGROUND AND OBJECTIVES: To optimize the effectiveness of cognitive-behavior
      therapy (CBT) for each individual patient, it is important to discern whether
      different intervention techniques may be differentially effective. One factor
      influencing the differential effectiveness of CBT intervention techniques may be
      the patient's preferred learning style, and whether this is 'matched' to the
      intervention. METHOD: The current study uses a retrospective analysis to examine
      whether the impact of two common CBT interventions (thought records and
      behavioral experiments) is greater when the intervention is either matched or
      mismatched to the individual's learning style. RESULTS: Results from this study
      give some indication that greater belief change is achieved when the intervention
      technique is matched to participants' learning style, than when intervention
      techniques are mismatched to learning style. LIMITATIONS: Conclusions are limited
      by the retrospective nature of the analysis and the limited dose of the
      intervention in non-clinical participants. CONCLUSIONS: Results suggest that
      further investigation of the impact of matching the patient's learning style to
      CBT intervention techniques is warranted, using clinical samples with higher dose
      interventions.

PMID- 22651923
TI  - Lipids in biocalcification: contrasts and similarities between intimal and medial
      vascular calcification and bone by NMR.
AB  - Pathomechanisms underlying vascular calcification biogenesis are still
      incompletely understood. Biomineral from human atherosclerotic intimal plaques;
      human, equine, and bovine medial vascular calcifications; and human and equine
      bone was released from collagenous organic matrix by sodium hydroxide/sodium
      hypochlorite digestion. Solid-state (13)C NMR of intimal plaque mineral shows
      signals from cholesterol/cholesteryl esters and fatty acids. In contrast, in
      mineral from pure medial calcifications and bone mineral, fatty acid signals
      predominate. Refluxing (chloroform/methanol) intimal plaque calcifications
      removes the cholesterylic but not the fatty acyl signals. The lipid composition
      of this refluxed mineral now closely resembles that of the medial and bone
      mineral, which is unchanged by reflux. Thus, intimal and medial vascular
      calcifications and bone mineral have in common a pool of occluded mineral
      entrained fatty acyl-rich lipids. This population of fatty acid may contain
      methyl-branched fatty acids, possibly representing lipoprotein particle remnants.
      Cell signaling and mechanistic parallels between physiological (orthotopic) and
      pathological (ectopic) calcification are also reflected thus in the NMR
      spectroscopic fingerprints of mineral-associated and mineral-entrained lipids.
      Additionally the atherosclerotic plaque mineral alone shows a significant
      independent pool of cholesterylic lipids. Colocalization of mineral and lipid may
      be coincidental, but it could also reflect an essential mechanistic component of
      biomineralization.

PMID- 22651924
TI  - Serological investigations on West Nile virus in birds and horses in Shanghai,
      China.
AB  - West Nile virus (WNV) infection is an emerging zoonosis that threatens global
      public health. In this study, a total of 95 bird serum samples from 14 species
      and 341 horse serum samples were collected from 2008 to 2010 in Shanghai, China.
      All serum samples were screened initially for WNV-reactive antibodies using a
      competitive ELISA. The positive samples detected by ELISA were further confirmed
      using a plaque-reduction neutralization test (PRNT) for WNV and its most closely
      related flaviviruses in the area to avoid false positives due to cross
      reactivity. Five (5.3%) of the bird serum samples and none (0.0%) of the horse
      serum samples tested positive for WNV antibodies. The findings strongly suggest
      that some of the birds, specifically the resident birds in China, had been
      exposed to WNV.

PMID- 22651925
TI  - Alteration of antral and proximal colonic motility induced by chronic
      psychological stress involves central urocortin 3 and vasopressin in rats.
AB  - Because of the difficulties in developing suitable animal models, the
      pathogenesis of stress-induced functional gastrointestinal disorders is not well
      known. Here we applied the communication box technique to induce psychological
      stress in rats and then examined their gastrointestinal motility. We measured
      upper and lower gastrointestinal motility induced by acute and chronic
      psychological stress and examined the mRNA expression of various neuropeptides in
      the hypothalamus. Chronic psychological stress disrupted the fasted motility in
      the antrum and accelerated motility in the proximal colon. mRNA expression of
      AVP, oxytocin, and urocortin 3 was increased by chronic psychological stress.
      Intracerebroventricular (ICV) injection of urocortin 3 disrupted the fasted
      motility in the antrum, while ICV injection of Ucn3 antiserum prevented
      alteration in antral motility induced by chronic psychological stress. ICV
      injection of AVP accelerated colonic motility, while ICV injection of SSR 149415,
      a selective AVP V1b receptor antagonist, prevented alteration in proximal colonic
      motility induced by chronic psychological stress. Oxytocin and its receptor
      antagonist L 371257 had no effect on colonic motility in either the normal or
      chronic psychological stress model. These results suggest that chronic
      psychological stress induced by the communication box technique might disrupt
      fasted motility in the antrum via urocortin 3 pathways and accelerates proximal
      colonic motility via the AVP V1b receptor in the brain.

PMID- 22651926
TI  - Dietary 1-monoolein decreases postprandial GIP release by reducing jejunal
      transport of glucose and fatty acid in rodents.
AB  - Postprandial secretion of insulin and glucose-dependent insulinotropic
      polypeptide (GIP) is differentially regulated by not only dietary carbohydrate
      but also fat. Recent studies have shown that the ingestion of diacylglycerol
      (DAG) results in lower postprandial insulin and GIP release than that of
      triacylglycerol (TAG), suggesting a possible mechanism for the antiobesity effect
      of DAG. The structural and metabolic characteristics of DAG are believed to be
      responsible for its beneficial effects. This study was designed to clarify the
      effect of 1-monoacylglycerol [oleic acid-rich (1-MO)], the characteristic
      metabolite of DAG, on postprandial insulin and GIP secretion, and the underlying
      mechanism. Dietary 1-MO dose dependently stimulated whole body fat utilization,
      and reduced high-fat diet-induced body weight gain and visceral fat accumulation
      in mice, both of which are consistent with the physiological effect of dietary
      DAG. Although glucose-stimulated insulin and GIP release was augmented by the
      addition of fat, coingestion of 1-MO reduced the postprandial hormone release in
      a dose-dependent manner. Either glucose or fatty acid transport into the everted
      intestinal sacs and enteroendocrine HuTu-80 cells was also reduced by the
      addition of 1-MO. Reduction of either glucose or fatty acid transport or the
      nutrient-stimulated GIP release by 1-MO was nullified when the intestine was
      pretreated with sodium-glucose cotransporter-1 (SGLT-1) or fatty acid translocase
      (FAT)/CD36 inhibitor. We conclude that dietary 1-MO attenuates postprandial GIP
      and insulin secretion by reducing the intestinal transport of the GIP
      secretagogues, which may be mediated via SGLT-1 and FAT/CD36. Reduced secretion
      of these anabolic hormones by 1-MO may be related to the antiobesity effect of
      DAG.

PMID- 22651927
TI  - Prevalence of undiagnosed HIV infection in the general population having blood
      tests within primary care in Madrid, Spain.
AB  - OBJECTIVE: To estimate the prevalence of undiagnosed HIV infection in men and
      women aged 16-80 years, having blood tests within primary care in Madrid, Spain.
      METHODS: A serosurvey to monitor vaccine-preventable diseases in the general
      population aged 16-80 years was conducted in 2008-2009. Eligible individuals were
      those having blood tests. The blood extraction centres, the primary sampling
      units, were chosen in proportion to the size and socio-economic characteristics
      of the target population, aiming for a sample size of 5355 subjects with equal
      sex distribution within five age bands. Migrants aged 16-40 years were
      oversampled. Previous HIV diagnoses were excluded. Prevalence rates of HIV
      infection with 95% CIs were estimated allocating weights inverse to their
      probability of selection. RESULTS: Overall, 3695 subjects agreed to participate,
      yielding a response rate of 69%, similar for men (66%) and women (73%);
      individuals recruited at healthcare centres or by telephone; and for all age
      groups except those aged >=60 (57%) years. HIV infection was diagnosed in 12
      subjects (0.35%; 95% CI 0.13 to 0.57); prevalence, higher in men (0.51%; 95% CI
      0.12 to 0.89) than in women (0.20%; 95% CI 0.00 to 0.44); participants from other
      countries (0.61%; 95% CI 0.03 to 1.18) as compared with Spanish born (0.30%; 95%
      CI 0.06 to 0.53) and aged 21-30 years (0.65%; 95% CI 0.01 to 1.29), or 31-40
      years (0.71%; 95% CI 0.02 to 1.41). None of the differences were statistically
      significant. Most of the 12 subjects were under follow-up for medical conditions;
      11 had visited the primary care clinic in the preceding month. CONCLUSION: The
      prevalence of undiagnosed HIV infection is very high and calls for strategies to
      unveil occult HIV infection.

PMID- 22651928
TI  - Acyclic retinoid targets platelet-derived growth factor signaling in the
      prevention of hepatic fibrosis and hepatocellular carcinoma development.
AB  - Hepatocellular carcinoma (HCC) often develops in association with liver
      cirrhosis, and its high recurrence rate leads to poor patient prognosis. Although
      recent evidence suggests that peretinoin, a member of the acyclic retinoid
      family, may be an effective chemopreventive drug for HCC, published data about
      its effects on hepatic mesenchymal cells, such as stellate cells and endothelial
      cells, remain limited. Using a mouse model in which platelet-derived growth
      factor (PDGF)-C is overexpressed (Pdgf-c Tg), resulting in hepatic fibrosis,
      steatosis, and eventually, HCC development, we show that peretinoin significantly
      represses the development of hepatic fibrosis and tumors. Peretinoin inhibited
      the signaling pathways of fibrogenesis, angiogenesis, and Wnt/beta-catenin in
      Pdgf-c transgenic mice. In vitro, peretinoin repressed the expression of PDGF
      receptors alpha/beta in primary mouse hepatic stellate cells (HSC), hepatoma
      cells, fibroblasts, and endothelial cells. Peretinoin also inhibited PDGF-C
      activated transformation of HSCs into myofibroblasts. Together, our findings show
      that PDGF signaling is a target of peretinoin in preventing the development of
      hepatic fibrosis and HCC.

PMID- 22651929
TI  - Identification of a molecular signature underlying inhibition of mammary
      carcinoma growth by dietary N-3 fatty acids.
AB  - An increased ratio of dietary n-3 relative to n-6 fatty acids has been shown to
      inhibit the development of mammary cancer in animal models. However, the
      molecular mechanisms by which n-3 fatty acids affect tumor growth remain unknown.
      Here, we investigated the effects of varying dietary ratios of n-3:n-6 fatty
      acids on cell signaling in a rat model of chemically induced mammary carcinoma.
      Cell proliferation was reduced by 60% in carcinomas from the high n-3:n-6
      treatment group compared with the low n-3:n-6 treatment group. These changes were
      associated with decreased cyclin-D1 and phospho-retinoblastoma protein expression
      and increased levels of cyclin-dependent kinase inhibitors, CIP1 (p21) and KIP1
      (p27). In addition, the apoptotic index was increased in carcinomas from the high
      n-3:n-6 group and was associated with elevated apoptotic protease-activating
      factor 1 and a higher ratio of Bax/Bcl-2. Interestingly, changes in protein
      expression were consistent with reduced inflammation and suppressed mTOR
      activity, and the molecular signature associated with high n-3:n-6 treatment
      revealed changes in PPARgamma activation and suppression of lipid synthesis.
      Together, our findings indicate that the molecular effects of high dietary n-3 to
      n-6 ratios are heterogeneous in nature but point to consistent changes in lipid
      metabolism pathways, which may serve as potential therapeutic targets for cancer
      prevention and control. This study identifies the pathways modulated by dietary
      fatty acid ratios in a rat model of breast cancer, with implications for cancer
      prevention.

PMID- 22651930
TI  - Detection of HPAI H5N1 viruses in ducks sampled from live bird markets in
      Vietnam.
AB  - In Vietnam, highly pathogenic avian influenza (HPAI) H5N1 infections in poultry
      often occur without concomitant clinical signs and outbreaks are not consistently
      reported. Live bird markets represent a convenient site for surveillance that
      does not rely on farmers' notifications. Two H5N1 surveys were conducted at live
      bird markets/slaughter points in 39 districts (five provinces) in the Red River,
      Mekong delta, and central Vietnam during January and May 2011. Oropharyngeal and
      rectal swab samples from 12 480 ducks were tested for H5N1 by reverse
      transcription-polymerase chain reaction in pools of five. Traders and
      stallholders were interviewed using standardized questionnaires; 3.3% of pools
      tested positive. The highest prevalence (6.6%) corresponded to the Mekong delta,
      and no H5N1 was detected in the two Red River provinces. The surveys identified
      key risk behaviours of traders and stallholders. It is recommended that market
      surveys are implemented over time as a tool to evaluate progress in HPAI control
      in Vietnam.

PMID- 22651931
TI  - A pleckstrin homology-related domain in SHIP1 mediates membrane localization
      during Fcgamma receptor-induced phagocytosis.
AB  - SH2 domain-containing inositol-5'-phosphatase-1 (SHIP1) inhibits inflammation by
      hydrolyzing phosphoinositide-3'-kinase generated membrane phosphatidylinositol
      3,4,5-trisphosphate (PIP(3)). Bioinformatic analysis of SHIP1 from multiple
      species revealed a pleckstrin homololgy-related (PH-R) domain, which we
      hypothesize mediates SHIP1's association with the membrane, a requirement for its
      biological function. Recombinant murine SHIP1 PH-R domain was subjected to
      biophysical and biochemical analysis. Residues K370 and K397 were found to be
      important for PH-R domain association with membrane PIP(3). Wild-type PH-R domain
      bound PIP(3) with 1.9 +/- 0.2 nM affinity, while the affinity of a K370A/K397A
      substituted mutant was too low to measure. Wild-type (but not the K370A/K397A
      substituted) full-length SHIP1 protein, reconstitutes normal inhibition of
      Fcgamma receptor-mediated phagocytosis when introduced into SHIP1(-/-) murine
      macrophages, reducing the number of phagocytic events by 2-fold as compared to
      SHIP1(-/-) cells. In fact, the PH-R-mediated membrane interaction appears to be a
      major mechanism by which SHIP1 is recruited to the membrane, since the
      K370A/K397A substitution reduced the recruitment of both full-length SHIP1 and
      the PH-R domain by >=2-fold. We have previously shown that SHIP1 enzyme activity
      can be targeted for therapeutic purposes. The current studies suggest that
      molecules targeting the PH-R domain can also modulate SHIP1 function.

PMID- 22651932
TI  - Generation of complement component C5a by ischemic neurons promotes neuronal
      apoptosis.
AB  - C5a receptors are found in the central nervous system (CNS), on both neurons and
      glia. However, the origin of the C5a, which activates these receptors, is
      unclear. In the present study, we show that primary cultured mouse cortical
      neurons constitutively express C5, the precursor of C5a, and express the
      classical receptor for C5a, CD88. With cell ischemia caused by 12 h glucose
      deprivation, or oxygen-glucose deprivation (OGD), neurons demonstrated increased
      apoptosis, up-regulation of CD88, and increased levels of C5a in the media.
      Exogenous murine C5a (100 nM) added to the neuronal cultures resulted in
      apoptosis, without affecting cell necrosis. Pretreatment of the cells with the
      specific CD88 receptor antagonist PMX53 (100 nM) significantly blocked ischemia
      induced apoptosis (~50%), and neurons from CD88(-/-) mice were similarly
      protected. In a murine model of stroke, using middle cerebral artery occlusion
      (MCAO), we found that C5a levels in the brain increased; this also occurred in
      cerebral slice cultures exposed to OGD. CD88(-/-) mice subjected to MCAO had
      significantly reduced infarct volumes and improved neurological scores. Taken
      together, our results demonstrate that neurons in the CNS have the capability to
      generate C5a following ischemic stress, and this has the potential to activate
      their C5a receptors, with deleterious consequences.

PMID- 22651933
TI  - The atypical chemokine receptor D6 controls macrophage efferocytosis and cytokine
      secretion during the resolution of inflammation.
AB  - The resolution of acute inflammation is hallmarked by the apoptotic death of
      inflammatory polymorphonuclear (PMN) cells, followed by their clearance by
      macrophages. In turn, resolution-phase macrophages exert reduced proinflammatory
      cytokine production, termed immune silencing. In this study, we found that the
      atypical chemokine receptor D6 plays an important and chemokine scavenging
      independent role in promoting macrophage-mediated resolution. D6(-/-) mice
      displayed increased numbers of macrophages (2.2-fold increase), but not
      neutrophils, in their peritonea during the resolution of murine zymosan A
      initiated peritonitis, in comparison to D6(+/+) animals. Moreover, D6-deficient
      macrophages engulfed higher numbers of apoptotic PMN cells in vivo (1.6-fold
      increase), and secreted higher amounts of TNF-alpha, CCL3, and CCL5 ex vivo than
      their wild-type (WT) counterparts. In addition, D6 was found to be expressed on
      apoptotic neutrophils from healthy humans and rodents. Moreover, the immune
      silencing of LPS-stimulated macrophages following their incubation with senescent
      PMN cells ex vivo (in terms of TNF-alpha, IL-1beta, and CCL5 secretion) was
      diminished (50-65% decrease) when D6(-/-) PMN cells were applied. Accordingly,
      the adhesive responses induced by macrophage interactions with senescent PMN
      cells were reduced with D6-deficient PMN cells. Thus, our results indicate a
      novel mode of action for D6 during the resolution of inflammation that is
      instrumental to the shaping of resolving macrophage phenotypes and the completion
      of resolution.

PMID- 22651934
TI  - Reversible regulation of aptamer activity with effector-responsive hairpin
      oligonucleotides.
AB  - Aptamers are oligonucleotides that can bind to various nonnucleic acid molecular
      targets in a high affinity and specificity. As an emerging class of therapeutic
      agents, aptamers offer an unparalleled advantage over other classes of
      therapeutic agents: the possibility to rationally regulate the therapeutic
      activity of aptamers. Most existing strategies for regulating the aptamer
      activity have a limited specificity and/or reversibility. Herein we report a
      simple, generic strategy to simultaneously achieve specificity and reversibility
      by exploiting the spontaneous conformational change of hairpin oligonucleotides
      upon the specific recognition of nucleic acid effectors. The effector-responsive
      hairpin oligonucleotide consists of a sensing loop that recognizes a particular
      nucleic acid effector, an aptamer stem that inhibits a certain therapeutic
      target, and an antidote stem that is complementary to the aptamer. Upon the
      introduction/removal of the effector, the hairpin oligonucleotide undergoes a
      conformational change that activates/deactivates the aptamer's inhibiting
      activity on the therapeutic target. This new strategy has been demonstrated with
      an anticoagulant aptamer that binds and inhibits human alpha-thrombin.

PMID- 22651935
TI  - Integration of data systems and technology improves research and collaboration
      for a superfund research center.
AB  - Large collaborative centers are a common model for accomplishing integrated
      environmental health research. These centers often include various types of
      scientific domains (e.g., chemistry, biology, bioinformatics) that are integrated
      to solve some of the nation's key economic or public health concerns. The
      Superfund Research Center (SRP) at Oregon State University (OSU) is one such
      center established in 2008 to study the emerging health risks of polycyclic
      aromatic hydrocarbons while using new technologies both in the field and
      laboratory. With outside collaboration at remote institutions, success for the
      center as a whole depends on the ability to effectively integrate data across all
      research projects and support cores. Therefore, the OSU SRP center developed a
      system that integrates environmental monitoring data with analytical chemistry
      data and downstream bioinformatics and statistics to enable complete "source-to
      outcome" data modeling and information management. This article describes the
      development of this integrated information management system that includes
      commercial software for operational laboratory management and sample management
      in addition to open-source custom-built software for bioinformatics and
      experimental data management.

PMID- 22651936
TI  - Biomek 3000: the workhorse in an automated accredited forensic genetic
      laboratory.
AB  - We have implemented and validated automated protocols for a wide range of
      processes such as sample preparation, PCR setup, and capillary electrophoresis
      setup using small, simple, and inexpensive automated liquid handlers. The
      flexibility and ease of programming enable the Biomek 3000 to be used in many
      parts of the laboratory process in a modern forensic genetics laboratory with low
      to medium sample throughput. In conclusion, we demonstrated that sample
      processing for accredited forensic genetic DNA typing can be implemented on small
      automated liquid handlers, leading to the reduction of manual work as well as
      increased quality and throughput.

PMID- 22651937
TI  - The role of biomarkers in evaluating human health concerns from fungal
      contaminants in food.
AB  - Mycotoxins are toxic secondary metabolites that globally contaminate an estimated
      25 % of cereal crops and thus exposure is frequent in many populations.
      Aflatoxins, fumonisins and deoxynivalenol are amongst those mycotoxins of
      particular concern from a human health perspective. A number of risks to health
      are suggested including cancer, growth faltering, immune suppression and neural
      tube defects; though only the demonstrated role for aflatoxin in the aetiology of
      liver cancer is widely recognised. The heterogeneous distribution of mycotoxins
      in food restricts the usefulness of food sampling and intake estimates; instead
      biomarkers provide better tools for informing epidemiological investigations.
      Validated exposure biomarkers for aflatoxin (urinary aflatoxin M(1), aflatoxin-N7
      guaunine, serum aflatoxin-albumin) were established almost 20 years ago and were
      critical in confirming aflatoxins as potent liver carcinogens. Validation has
      included demonstration of assay robustness, intake v. biomarker level, and
      stability of stored samples. More recently, aflatoxin exposure biomarkers are
      revealing concerns of growth faltering and immune suppression; importantly, they
      are being used to assess the effectiveness of intervention strategies. For
      fumonisins and deoxynivalenol these steps of development and validation have
      significantly advanced in recent years. Such biomarkers should better inform
      epidemiological studies and thus improve our understanding of their potential
      risk to human health.

PMID- 22651938
TI  - Outcomes of total or near-total lip reconstruction with microvascular tissue
      transfer.
AB  - PURPOSE: The reconstruction of total lower lip defects is very challenging,
      whether from trauma or after oncologic treatment. The challenge faced by surgeons
      is to re-create not only an esthetically pleasing lower lip but also, more
      importantly, a lip that is functional. MATERIALS AND METHODS: The authors
      reviewed their experience at the Division of Oral and Maxillofacial Surgery,
      University of Florida College of Medicine, Jacksonville in reconstructing these
      challenging defects over a 3 year period. The timeline extended from 2007 through
      2010. All surgeries were performed by the senior author. The medical records were
      reviewed to retrieve demographics, including age, gender, reasons for the
      acquired defect, lip reconstructed, reconstructive method, flap survival, and
      outcomes. RESULTS: Twelve patients with 13 free tissue transfers for total or
      near total lip defects reconstructed with free tissue transfer were identified.
      The patients' mean age was 57 years, and the overwhelming majority of patients
      were men (10 vs 2). The defects were due to resection of malignancies affecting
      the lip in 10 patients and to avulsive gunshot injuries in 2 patients. Of the 13
      flaps used to reconstruct the defects, 11 were radial forearm flaps using the
      palmaris longus tendon and 1 was an anterolateral thigh flap using the fascia to
      resuspend the lip. There was a 100% survival rate of the flaps. Postoperatively,
      all patients were able to take oral diet and none of the patients complained of
      drooling, an inability to eat in a public setting, or microstomia. Of the
      patients who underwent reconstruction, 8 received pre- or postoperative radiation
      therapy and the remaining 4 patients did not. CONCLUSIONS: In this case series,
      the radial forearm free flap was the most commonly used flap for lip
      reconstruction. The use of free tissue transfer for lip reconstruction is a very
      predictable method for reconstructing these challenging defects and maintaining a
      patient's ability to take in an oral diet. Although there was a clear color
      mismatch in most patients, none viewed this as a major drawback of the
      reconstruction.

PMID- 22651939
TI  - Decreased gray matter diffusivity: a potential early Alzheimer's disease
      biomarker?
AB  - BACKGROUND: Gray matter atrophy, an important biomarker for early Alzheimer's
      disease, might be due to white matter changes within gray matter. METHODS: Twenty
      older participants with significant memory decline over a 12-year period (T12)
      were matched to 20 nondeclining participants. All participants were magnetic
      resonance imaging scanned at T12. Cortical thickness and diffusion tensor imaging
      analyses were performed. RESULTS: Lower cortical thickness values were associated
      with lower diffusion values in frontal and parietal gray matter areas. This
      association was only present in the memory decline group. The cortical thickness
      diffusion tensor imaging correlations showed significant group differences in the
      posterior cingulate gyrus, precuneus, and superior frontal gyrus. CONCLUSIONS:
      Decreased gray matter diffusivity in the posterior cingulate/precuneus area might
      be a disease-specific process and a potential new biomarker for early Alzheimer's
      disease. Future studies should validate its potential as a biomarker and focus on
      cellular changes underlying diffusivity changes in gray matter.

PMID- 22651940
TI  - The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two
      Caucasian case-control cohorts.
AB  - BACKGROUND: Human sirtuins are a current hotspot for research in
      neurodegenerative disorders, including Alzheimer's disease (AD). This study
      investigated whether genetic variants in two members of the sirtuin family, SIRT2
      and SIRT3, affected AD susceptibility. METHODS: A genetic case-control study was
      performed, comprising 534 probable AD cases and 638 nondemented control subjects
      from the north of Italy and Canton Ticino, Switzerland (discovery population).
      The study was focused on SIRT2 rs10410544, SIRT3 rs4980329, and SIRT3 rs536715
      single nucleotide polymorphisms (SNPs). These SNPs were genotyped by real-time
      polymerase chain reaction allelic discrimination assay or restriction fragment
      length polymorphism. The SNPs rs7412 and rs429358, mapping within the
      apolipoprotein E (APOE) gene, were genotyped by real-time polymerase chain
      reaction allelic discrimination assay too. In a replication population comprising
      756 AD cases and 847 nondemented control subjects, SIRT2 rs10410544, APOE rs7412,
      and APOE rs429358 were genotyped as mentioned previously. RESULTS: In the
      discovery population, we observed an association between SIRT2 rs10410544 T
      allele and AD (adjusted odds ratio [OR] = 1.23, 95% confidence interval [CI]:
      1.02-1.50, P = .02, after correction for sex, age, and APOE epsilon4 genotype).
      The association between AD and SIRT2 rs10410544 T allele was only present in APOE
      epsilon4 noncarriers (adjusted OR = 1.29, 95% CI: 1.03-1.61, P = .03). The
      replication study did not confirm this evidence. However, the combined analysis
      on the two cohorts detected the association (adjusted OR = 1.17, 95% CI: 1.02
      1.35, P = .02), and only APOE epsilon4 noncarriers were at risk (adjusted OR =
      1.2, 95% CI: 1.02-1.43, P = .03). CONCLUSIONS: The SIRT2 rs10410544 T allele
      deserves further investigation as a novel minor genetic risk factor for AD in the
      APOE epsilon4-negative Caucasian population.

PMID- 22651941
TI  - Predictors for cognitive decline in patients with confluent white matter
      hyperintensities.
AB  - BACKGROUND: Although patients harboring confluent white matter hyperintensities
      (WMH) are at high risk of cognitive decline, this risk varies among individuals.
      We investigated the predictors for cognitive decline in stroke patients with
      confluent WMH. METHODS: We followed up 100 stroke patients with confluent WMH who
      were participants of the VITAmins TO Prevent Stroke study for 2 years. We
      investigated the association between clinical features, apolipoprotein E status,
      imaging measures (infarcts, microbleeds, volumes of WMH, cortical gray matter
      [cGM], lateral ventricles, and hippocampi), and B vitamins with changes in
      cognitive measures (clinical dementia rating scale, Mini-Mental State
      Examination, Mattis dementia rating scale--initiation/perseveration subscale). We
      performed Pittsburgh compound B imaging among dementia converters. RESULTS:
      Multivariate regression analysis showed that increase in clinical dementia rating
      scale grade was associated with cGM atrophy, absence of hyperlipidemia, and lower
      diastolic blood pressure at baseline. cGM atrophy and absence of hyperlipidemia
      were also associated with deterioration in Mini-Mental State Examination and
      Mattis dementia rating scale--initiation/perseveration subscale scores.
      Pittsburgh compound B retention typical of Alzheimer's disease was found only in
      10% of dementia converters. Incident stroke and B vitamins were not associated
      with cognitive decline. CONCLUSIONS: Among stroke patients with confluent WMH,
      cGM atrophy and absence of hyperlipidemia are important predictors for cognitive
      decline. Significant cognitive decline can occur in the absence of incident
      stroke or Alzheimer's pathology.

PMID- 22651942
TI  - Risk of dementia in an elderly population of Parkinson's disease patients: a 15
      year population-based study.
AB  - BACKGROUND: The incidence of dementia in Parkinson's disease (PD) is not fully
      known, and previous studies have provided a wide range of rates owing to
      variations in diagnostic criteria and methodologies used. We estimated the risk
      of dementia in newly diagnosed cases of PD in a population-based cohort of
      subjects aged >65 years. METHODS: We performed repetitive systematic screening of
      PD diagnosis, cognitive performances, and clinical dementia during 15 years (at
      year 0, 3, 5, 8, 10, and 15) in 3726 elderly subjects living at home in
      southwestern France (PAQUID). Two sets of diagnostic criteria for dementia in PD
      were considered: Diagnostic and Statistical Manual of Mental Disorders, Third
      Edition, Revised criteria and Movement Disorders Society criteria. RESULTS: Forty
      four incident cases of PD occurred in the cohort; of these, 18 (41%) developed
      dementia during a mean follow-up of 6.8 +/- 3.6 years. Incidence rate of dementia
      associated with PD was 74 per 1000 patient-years. The cumulative risk of dementia
      was approximately 25% and 50% after 5 and 10 years of follow-up, respectively.
      The relative risk for developing dementia in incident PD subjects compared with
      non-PD subjects was 2.47 (1.55-3.95). Equivalent estimations were obtained with
      Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised
      criteria or Movement Disorders Society criteria. CONCLUSION: PD represents a high
      risk stage for dementia in the general population.

PMID- 22651943
TI  - Obstructive sleep apnea and carotid intima media thickness? Can we assume an
      independent association?

PMID- 22651944
TI  - Key characteristics of palliative care studies reported in the specialized
      literature.
AB  - CONTEXT: Although research activity in palliative care is rapidly increasing, the
      composition of published studies--in terms of significant research
      characteristics--has not yet been well described. OBJECTIVES: To describe the
      topics of and funding for palliative care studies reported in the three hospice
      and palliative care journals with the highest impact factors (Journal of Pain and
      Symptom Management, Palliative Medicine, and Journal of Palliative Medicine).
      METHODS: This was a substudy of a larger bibliographic study. The targeted
      journals were searched for 2007 using a previously validated Ovid MEDLINE filter
      for palliative care. All empirical palliative care studies were included.
      Articles were classified according to topics (palliative care patient,
      caregiver/family, health professional, service provision, tool development,
      healthy volunteer, medication compatibility, community), study type
      (intervention, nonintervention), country of origin, and funding source
      (pharmaceutical company, other funder, unfunded). RESULTS: Of 409 citations
      identified, the search yielded 189 eligible articles. Most articles were
      descriptive/observational. Approximately half were unfunded. Caregivers, healthy
      volunteers, and health service research were the least frequent topics for
      research. Only five randomized controlled trials were reported. CONCLUSION:
      Although there is a broad range of research undertaken in palliative care, few
      studies generate high-level evidence, with data showing a relative lack of
      funding for hospice and palliative care studies.

PMID- 22651945
TI  - The prevalence of bowel problems reported in a palliative care population.
AB  - CONTEXT: Constipation and other disturbances of bowel function are distressing
      problems for people with specialist palliative care needs. Recent observations
      suggest that such problems may worsen as people become more unwell, but the
      changes in intensity over time are not well documented. OBJECTIVES: The
      objectives of this work were to understand the prevalence, intensity, and
      progression of self-reported bowel disturbances across a community palliative
      care population, which included people with cancer and noncancer diagnoses.
      METHODS: All people referred to a community-based palliative care service over a
      period of 6.3 years had their bowel problem scores reported, using a numerical
      rating score at every clinical encounter until their death, at four discrete time
      points, namely, 90, 60, 30, and seven days before death. This allowed change over
      three time periods to be considered. At the same time, other symptom scores were
      collected including nausea, fatigue, pain, appetite problems, and breathing
      problems. Patients were categorized according to the underlying disease that
      accounted for their referral to palliative care, namely, cancer diagnoses (upper
      gastrointestinal cancers, lower gastrointestinal cancers, cancers of the
      associated digestive organs, and other cancers) and nonmalignant diagnoses. Group
      differences over the time periods were assessed using analysis of variance.
      Bivariate analysis was used to explore the relationship between bowel
      disturbances and other symptoms using Spearman's Rho correlation. RESULTS: For
      7772 patients, data were collected an average of 22.5 times, generating 174,783
      data collection points over an average of 98.6 days on the service. At the time
      of referral to the service, 3248 (42.4%) people had disturbed bowel scores, 548
      (7.2%) of whom described these as severe. Only 1020 (13.1%) people never
      described disturbed bowel function over their time in palliative care. At each
      time point, approximately one-third were experiencing disturbed bowel function,
      with proportionally greater numbers of people experiencing more significant
      problems as death approached (Chi(2) (9)=119.3; P<0.001). Most referrals to the
      service were because of cancer diagnoses, with no significant differences noted
      between the bowel disturbance scores of those with cancer diagnoses compared with
      those with nonmalignant disease. Associations between bowel problem score and
      appetite problems, nausea, breathing problems, fatigue, and pain were explored.
      Although weak, there were statistically significant associations between all
      symptoms and bowel problem scores except for breathing problems. CONCLUSION: In
      conclusion, disturbed bowel function consistently remains a problem for people
      under the care of palliative care services, with the proportion of people with
      severe problems increasing as death approaches. This is despite the time and
      number of interventions currently used to palliate these problems.

PMID- 22651946
TI  - Effect of parenteral hydration therapy based on the Japanese national clinical
      guideline on quality of life, discomfort, and symptom intensity in patients with
      advanced cancer.
AB  - CONTEXT: Although an evidence-based clinical guideline for parenteral hydration
      therapy was established in Japan, the efficacy of the guideline has not been
      assessed. OBJECTIVES: Our purpose was to explore the effect of parenteral
      hydration therapy based on this clinical guideline on quality of life (QoL),
      discomfort, symptoms, and fluid retention signs in patients with advanced cancer.
      METHODS: This multicenter, prospective, observational study included 161 patients
      with advanced abdominal cancer who received guideline-based hydration therapy. We
      evaluated the longitudinal changes of the global QoL (Item 30 of European
      Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire
      C30); the Discomfort Scale; the intensity of seven physical symptoms; and the
      severity of fluid retention signs. We also evaluated patient satisfaction and the
      feeling of benefit from hydration one week after the study commenced, and
      bronchial secretions, hyperactive delirium, communication capacity, and agitation
      48 hours before a patient's death. RESULTS: The global QoL, the Discomfort Scale,
      and the intensities of all physical symptoms, except for vomiting and drowsiness,
      were stable throughout the study period. More than 80% of patients maintained all
      fluid retention signs. Patient global satisfaction was 76.4 (0-100) and feeling
      of benefit was 5.43 (range 0-7). CONCLUSION: Guideline-based parenteral hydration
      therapy contributed to maintaining global QoL and provided satisfaction and a
      feeling of benefit without increasing discomfort and worsening symptoms and fluid
      retention signs in patients with advanced cancer.

PMID- 22651947
TI  - When expectations predict experience: the influence of psychological factors on
      chemotherapy toxicities.
AB  - CONTEXT: Patients with cancer undergoing similar treatments experience variable
      severity and frequency of side effects not adequately explained by
      pharmacological mechanisms, suggesting psychological influence. OBJECTIVES:
      First, this study aimed to further examine the relationship between patients'
      expectations of multiple chemotherapy-related toxicities and experiences. Second,
      this study aimed to explore the impact of anxiety and cancer coping styles to aid
      in informing interventions to lessen such expectations. METHODS: A total of 59
      eligible, consenting patients with cancer rated their expectations of 20
      chemotherapy toxicities on 100-point linear analogue self-assessment indicators
      before treatment and completed the Spielberger State Anxiety Inventory and the
      Mental Adjustment to Cancer scale. Patients then rated their experience of side
      effects after one chemotherapy session. RESULTS: Regressions controlling primary
      treating nurse influence and patient performance status showed toxicity
      experience was significantly predicted by patient expectations of mood changes,
      bleeding, skin itchiness, hair loss, feeling tired, and sleep disturbance
      (beta=0.30-0.55). Anxiety was significantly related to expectations of
      nervousness and mood changes; the coping style Fighting Spirit showed no
      significant associations, whereas conversely, Anxious Preoccupation showed some
      degree of association with all 20 toxicities (r=0.11-0.34). CONCLUSION: Findings
      support the growing contention that patient expectations influence experience,
      negatively impacting quality of life. As it is unethical to withhold treatment
      information, research into screening for at-risk patients and offering brief
      interventions to minimize Anxious Preoccupation could be one way to reduce
      overall side effect burden, perhaps in the case of many medical interventions.

PMID- 22651948
TI  - Inpatient palliative care and patient pain: pre- and post-outcomes.
AB  - CONTEXT: Hospitalized patients with serious illness often receive inadequate pain
      and symptom management at the end of life. OBJECTIVES: To test the effectiveness
      of an interdisciplinary inpatient palliative care (IPC) consultation program in
      the management of pain among seriously ill patients during hospitalization, and
      to examine IPC patient pain outcomes 10 days following hospital discharge.
      METHODS: A two-year pre-post study was conducted at a nonprofit health
      maintenance organization medical center in Los Angeles County. Hospital patients
      (n = 484) aged 65 years and older with life-threatening, complex, chronic
      conditions received comprehensive assessment, pain and symptom relief, care
      planning, counseling, and other supportive services from an IPC team. Measures
      included self-reported pain at baseline, two and 24 hours following IPC
      intervention, discharge, and 10 days post-discharge. RESULTS: Mean pain was
      significantly different between baseline (1.56 +/- 2.79) and two hours (0.91 +/-
      1.59; P < 0.001), 24 hours (0.77 +/- 1.58; P < 0.001), and hospital discharge
      (0.40 +/- 1.09; P < 0.001). Mean pain 10 days after discharge (2.04 +/- 2.79; P <
      0.001) was significantly higher than mean pain at discharge. Number of chronic
      conditions, probability of mortality, and discharge to hospice care significantly
      predicted increased pain following discharge. CONCLUSION: To the authors'
      knowledge, this is the first study to follow IPC patient pain after hospital
      discharge. Findings support IPC teams' effectiveness in managing pain during
      hospitalization but suggest a lack of continuity in pain management following
      discharge. Research exploring IPC patient post-discharge transition experiences
      will likely improve understanding of post-discharge pain outcomes.

PMID- 22651949
TI  - Hospice providers' key approaches to support informal caregivers in managing
      medications for patients in private residences.
AB  - CONTEXT: Managing and administering medications to relieve pain and symptoms are
      common, important responsibilities for informal caregivers of patients receiving
      end-of-life care at home. However, little is known about how hospice providers
      prepare and support caregivers with medication-related tasks. OBJECTIVES: This
      qualitative study explores the key approaches that hospice providers use to
      facilitate medication management for caregivers. METHODS: Semistructured, open
      ended interviews were conducted with 22 providers (14 nurses, four physicians,
      and four social workers) from four hospice organizations around an urban setting
      in the midwestern U.S. RESULTS: Based on the interviews, the following five key
      approaches emerged, constituting how the hospice team collectively helped
      caregivers manage medications: 1) establishing trust; 2) providing information;
      3) promoting self-confidence; 4) offering relief (e.g., provided in-home
      medication assistance, mobilized supportive resources, and simplified
      prescriptions); and 5) assessing understanding and performance. Each hospice
      discipline used multiple approaches. Nurses emphasized tailoring information to
      individual caregivers and patients, providing in-home assistance to help relieve
      caregivers, and assessing caregivers' understanding and performance of medication
      management during home visits. Physicians simplified medication prescriptions to
      alleviate burden and reassured caregivers using their perceived medical
      authority. Social workers facilitated medication management by providing
      emotional support to promote self-confidence and mobilizing resources in
      caregivers' support networks and the community at large. CONCLUSION: Hospice
      nurses, physicians, and social workers identified distinct, yet overlapping,
      approaches in aiding caregivers with medication management. These findings
      emphasize the importance of interdisciplinary teamwork among hospice providers.
      Future research should investigate how common, standardized, effective, and
      efficient these approaches are in practice.

PMID- 22651950
TI  - Assessing the quality of pain care in ambulatory patients with advanced stage
      cancer.
AB  - CONTEXT: Pain is common among patients with advanced cancer despite the
      dissemination of clinical pain care guidelines. OBJECTIVES: We sought to assess
      the quality of pain care among patients with advanced disease. METHODS: We
      reviewed the records of 85 adult ambulatory patients with advanced breast, lung,
      and gastrointestinal cancer treated in 2004-2006. Patients' screening pain
      intensity scores were at least 7 of 10. Nurse reviewers completed medical record
      reviews of care rendered at the index visit and over the subsequent 30 days based
      on the 2004 National Comprehensive Cancer Network pain guideline. An expert panel
      then rated the quality of the evaluation, treatment, and overall pain care. We
      used a multivariable model to analyze guideline compliance and resolution of
      severe pain. RESULTS: Among advanced cancer patients with severe pain, clinicians
      adjusted pain medications only half the time and made few timely referrals for
      pain-related consultations. By 30 days after the index visit, 34% of patients
      continued to report severe pain. The expert panel judged the overall quality of
      pain care as "fair" or "poor" in about two-thirds of cases because more timely
      and effective intervention could have reduced the severity and duration of pain.
      Resolution of severe pain was associated with adjustment of pain medications at
      the index visit (adjusted odds ratio 3.8, 95% CI 1.3-10.6). CONCLUSION: There is
      room for improvement in the pain care of patients with advanced cancer.
      Additional research is needed to understand the reasons for poor performance.

PMID- 22651951
TI  - A case of inaccurate prognostication after the ARCTIC protocol.
AB  - Therapeutic hypothermia (ARCTIC, or Advanced Resuscitation Cooling Therapeutics
      and Intensive Care protocol) is a widely recommended intervention to improve
      mortality and neurologic outcomes after cardiac arrest. However, neurologic
      outcomes are difficult to predict soon after cardiac arrest in the setting of
      hypothermia, as illustrated by this case report. A 60-year-old man had witnessed
      cardiac arrest at home. He was defibrillated twice, with return of spontaneous
      circulation, and cooled to 33 degrees C for 24 hours. Neurologic exam on Day 6
      revealed limited brainstem reflexes, and the intensive care unit team discussed
      with the patient's family that his prognosis for neurologic recovery was poor.
      Palliative care was consulted to participate in a goals-of-care meeting. Just
      prior to the meeting on Day 7, the patient awoke. He fully recovered and walked
      out of the hospital on Day 18. Prior to induced hypothermia, indicators of poor
      outcome included lack of one or more brainstem reflexes (pupillary or corneal
      reflex), absence of motor response at 72 hours, myoclonus, status epilepticus,
      electroencephalogram with generalized suppression, and absent bilateral cortical
      N20 response to somatosensory-evoked potentials. However, several studies have
      found these indicators to be unreliable after hypothermia. This may be the result
      of sedatives, which can affect physical examination and electroencephalogram
      results, and delayed clearance. Because of the unreliability of prognostication
      tests within the first 72 hours of hypothermic protocols in the setting of
      sedation, it appears prudent in some cases to delay final prognosis discussions
      until at least six days postcardiac arrest and after neurologic evaluation is
      done with patients sedative-free.

PMID- 22651952
TI  - Palliative sedation in advanced cancer patients followed at home: a retrospective
      analysis.
AB  - CONTEXT: Data regarding palliative sedation at home in dying patients are
      lacking. OBJECTIVES: To describe the frequency, indication, and modality of
      palliative sedation (PS) in patients followed at home. METHODS: A retrospective
      analysis of home care cancer patients was performed. Patients who received PS
      before dying were selected and information about epidemiologic characteristics,
      indications, duration, drugs, and outcomes was collected. RESULTS: Of 370 medical
      charts of patients who died at home, 49 patients received PS before dying. PS was
      proposed by the team, relatives, or both in 63.3%, 4.1%, and 32.6% of cases,
      respectively. Delirium alone or in combination with other symptoms was the most
      frequent indication to begin PS. Midazolam was the most frequently used drug to
      initiate PS (98%), at a mean dose of 28.1 mg/day, in combination with parenteral
      morphine (84.7%) at a mean dose of 25.4 mg/day. At the time of death, midazolam
      was administered in 98% of patients (mean dose 22.3 mg/day), combined with
      parenteral morphine in 87.8% of patients (mean dose 28.1 mg/day). Satisfaction
      for physicians and principal caregivers after PS was good in 46 and 48 cases,
      respectively. CONCLUSION: PS at home seems to be a feasible treatment option
      among selected patients and makes a potentially important contribution to
      improving care for those who choose to die at home.

PMID- 22651953
TI  - Factor structure and psychometric properties of the Chinese version of the 20
      item Pain Anxiety Symptoms Scale (ChPASS-20).
AB  - CONTEXT: The Pain Anxiety Symptoms Scale (PASS) was designed to assess pain
      related anxiety and fear. Although the scale is a reliable measure with good
      psychometric properties, its validity among ethnic Chinese has yet to be
      evaluated. OBJECTIVES: This study aimed to translate the English-language version
      of the 20-item PASS into Chinese (ChPASS-20) and evaluate its factor structure,
      reliability, and validity. METHODS: A total of 223 Chinese patients with chronic
      musculoskeletal pain attending orthopedic specialist clinics completed the ChPASS
      20, the Chronic Pain Grade questionnaire, the Chinese version of the 11-item
      Tampa Scale of Kinesiophobia, the Hospital Anxiety and Depression Scale, and
      questions assessing sociodemographic and pain characteristics. RESULTS:
      Confirmatory factor analyses showed that all the five-factor solutions tested met
      the minimum acceptable fit criterion. The four ChPASS-20 subscales and the entire
      scale demonstrated good internal consistency (Cronbach's alphas: 0.72-0.92). All
      ChPASS-20 scales showed significant positive correlations with depression, pain
      intensity, and disability. Hierarchical multiple regression analyses showed that
      the ChPASS-20 total score predicted concurrent depression [F(4,159)=11.97,
      P<0.001], pain intensity [F(4,161)=2.47, P<0.05], and pain disability
      [F(4,191)=5.47, P<0.001] scores, and the ChPASS-20 Avoidance subscale
      (standardized beta coefficient=0.21, P<0.05) emerged as a significant independent
      predictor of concurrent pain disability. CONCLUSION: Our data support the
      factorial validity, reliability, and construct validity of the ChPASS-20 in a
      Chinese population.

PMID- 22651955
TI  - Deep brain drug delivery.

PMID- 22651954
TI  - Structural insights into the rodent CNS via diffusion tensor imaging.
AB  - Diffusion tensor imaging (DTI) is a useful tool for studying anatomy and
      pathology in the rodent central nervous system (CNS).The unique tissue contrasts
      provided by DTI are well suited for monitoring disease progression, studying
      brain development, and characterizing anatomical phenotypes. Recent technical
      developments have vastly improved the speed and resolution of rodent DTI. Ongoing
      research efforts exploring the microstructural basis of DTI signals have provided
      useful insights into its capabilities to delineate brain structures and detect
      neuropathology. Significant progress has also been made in combining DTI results
      with data acquired using other imaging modalities to enhance our understanding of
      the rodent CNS.

PMID- 22651956
TI  - Attention modulates 'speech-tracking' at a cocktail party.
AB  - Recent findings by Mesgarani and Chang demonstrate that signals in auditory
      cortex can reconstruct the spectrotemporal patterns of attended speech tokens
      better than those of ignored ones. These results help extend the study of
      attention into the domain of natural speech, posing numerous questions and
      challenges for future research.

PMID- 22651957
TI  - Reduced fear-recognition sensitivity following acute buprenorphine administration
      in healthy volunteers.
AB  - In rodents, the endogenous opioid system has been implicated in emotion
      regulation, and in the reduction of fear in particular. In humans, while there is
      evidence that the opioid antagonist naloxone acutely enhances the acquisition of
      conditioned fear, there are no corresponding data on the effect of opioid
      agonists in moderating responses to fear. We investigated whether a single 0.2mg
      administration of the mu-opioid agonist buprenorphine would decrease fear
      sensitivity with an emotion-recognition paradigm. Healthy human subjects
      participated in a randomized placebo-controlled within-subject design, in which
      they performed a dynamic emotion recognition task 120min after administration of
      buprenorphine and placebo. In the recognition task, basic emotional expressions
      were morphed between their full expression and neutral in 2% steps, and presented
      as dynamic video-clips with final frames of different emotional intensity for
      each trial, which allows for a fine-grained measurement of emotion sensitivity.
      Additionally, visual analog scales were used to investigate acute effects of
      buprenorphine on mood. Compared to placebo, buprenorphine resulted in a
      significant reduction in the sensitivity for recognizing fearful facial
      expressions exclusively. Our data demonstrate, for the first time in humans, that
      acute up-regulation of the opioid system reduces fear recognition sensitivity.
      Moreover, the absence of an effect of buprenorphine on mood provides evidence of
      a direct influence of opioids upon the core fear system in the human brain.

PMID- 22651958
TI  - LC-ESI-MS/MS analysis and pharmacokinetics of 6'-hydroxy justicidin A, a
      potential antitumor active component isolated from Justicia procumbens, in rats.
AB  - A sensitive and accurate LC-ESI-MS/MS method was developed and validated of for
      the determination of 6'-hydroxy justicidin A (HJA), a potential antitumor active
      component isolated from Justicia procumbens in rat plasma using a simple liquid
      liquid extraction (LLE) method for sample preparation. Chromatographic separation
      was achieved on an Agilent Zorbax-C(18) column (2.1 mm * 50 mm, 3.5 MUm) using a
      step gradient program with the mobile phase of 0.1% formic acid aqueous solution
      and acetonitrile with 0.1% formic acid. HJA and IS (buspirone) were detected
      using electrospray positive ionization mass spectrometry in the multiple reaction
      monitoring (MRM) mode. This method demonstrated good linearity and did not show
      any endogenous interference with the active compound and IS peaks. The lower
      limit of quantification (LLOQ) of HJA was 0.50 ng/ml in 50 MUl rat plasma. The
      developed and validated method has been successfully applied to the
      quantification and pharmacokinetic study of HJA in rats after intravenous and
      oral administration of 0.25 mg/kg HJA. The oral bioavailability (F) of HJA was
      estimated to be 36.0+/-13.4% with an elimination half-life (t(1/2)) value of
      1.04+/-0.20 h.

PMID- 22651959
TI  - Using immobilized G-protein coupled receptors to screen bioactive traditional
      Chinese medicine compounds with multiple targets.
AB  - Demand on high-throughput methods for multi-target compounds screening continues
      to increase nowadays due to the decline of new drugs on the market. Two kinds of
      G-protein-coupled receptors, alpha1-adrenoceptor (alpha(1A)-AR) and beta2
      adrenoceptor (beta(2)-AR), were purified and immobilized on the surface of
      macroporous silica gel to prepare new chromatographic stationary phases. Control
      drugs (e.g., prazosin, terazosin, salbutamol, and terbutaline) were used to
      characterize the retention behavior of the obtained alpha(1A)-AR and beta(2)-AR
      columns. This study also coupled both columns with a six-way switching valve to
      construct an automatic two-dimensional system for multi-target compounds
      screening in complex mixtures. Adrenaline hydrochloride was used as a
      representative drug to evaluate the chromatographic performance of the two
      dimensional system. The aqueous extracts from Salvia miltiorrhiza and Coptis
      chinensis were also analyzed by the automatic system. The compounds in S.
      miltiorrhiza had no binding to both alpha(1A)-AR and beta(2)-AR columns. But
      berberine, palmatine and jatrorrhizine were screened as the bioactive compounds
      in C. chinensis, targeting both the receptors. The proposed method is an
      alternative for recognizing and separating the compounds targeting different
      proteins from a complex matrix.

PMID- 22651961
TI  - Transcranial direct current stimulation for the treatment of major depressive
      disorder: a summary of preclinical, clinical and translational findings.
AB  - Major depressive disorder (MDD) is a common psychiatric illness, with 6-12%
      lifetime prevalence. It is also among the five most disabling diseases worldwide.
      Current pharmacological treatments, although relatively effective, present
      important side effects that lead to treatment discontinuation. Therefore, novel
      treatment options for MDD are needed. Here, we discuss the recent advancements of
      one new neuromodulatory technique--transcranial direct current stimulation (tDCS)
      -that has undergone intensive research over the past decade with promising
      results. tDCS is based on the application of weak, direct electric current over
      the scalp, leading to cortical hypo- or hyper-polarization according to the
      specified parameters. Recent studies have shown that tDCS is able to induce
      potent changes in cortical excitability as well as to elicit long-lasting changes
      in brain activity. Moreover, tDCS is a technique with a low rate of reported side
      effects, relatively easy to apply and less expensive than other neuromodulatory
      techniques--appealing characteristics for clinical use. In the past years, 4 of 6
      phase II clinical trials and one recent meta-analysis have shown positive results
      in ameliorating depression symptoms. tDCS has some interesting, unique aspects
      such as noninvasiveness and low rate of adverse effects, being a putative
      substitutive/augmentative agent for antidepressant drugs, and low-cost and
      portability, making it suitable for use in clinical practice. Still, further
      phase II and phase III trials are needed as to better clarify tDCS role in the
      therapeutic arsenal of MDD.

PMID- 22651960
TI  - Involvement of mGlu5 and NMDA receptors in the antidepressant-like effect of
      acamprosate in the tail suspension test.
AB  - Accumulating evidence supports the hypothesis that modulation of glutamatergic
      system via NMDA receptors and mGlu5 receptors might be an effective
      antidepressant therapy. However, clinical application of NMDA and mGlu5
      antagonists in the therapy of depression is still an open question. In the
      present study we investigated potential antidepressant-like effect of a
      functional NMDA and mGlu5 receptor antagonist, acamprosate, which has been used
      in the therapy of human alcoholics as an anti-craving drug for more than 20 years
      and is considered as a safe substance. We have found potential antidepressant
      like effect of acamprosate at doses of 100-400 mg/kg in the TST in C57BL/6J mice.
      Furthermore we have shown that the antidepressant-like effect of acamprosate used
      at a dose of 200 mg/kg was dependent on NMDA and mGlu5 receptor blockade, since
      NMDA (25 mg/kg) and mGlu5 receptor positive allosteric modulator, CDPPB (3
      mg/kg), antagonized its activity in the TST. These data suggest that acamprosate
      may induce antidepressant-like effect and that NMDA and mGlu5 receptors are
      crucial targets of acamprosate in this action.

PMID- 22651962
TI  - Cervical spine posteroanterior stiffness differs with neck position.
AB  - PURPOSE: Spinal stiffness is commonly considered when treating patients with neck
      pain, but there are few studies reporting the objective measurement of cervical
      spine stiffness or the possible kinesiological factors that may affect its
      quantification. The aim of this study was to determine if the position of the
      neck affects cervical spine stiffness. METHODS: An instrumented stiffness
      assessment device measured posteroanterior cervical spine stiffness at C4 of 25
      prone-lying asymptomatic subjects in three neck positions in randomised order:
      maximal flexion, maximal extension, and neutral. The device applied five
      standardised mechanical oscillatory pressures while measuring the applied force
      and concurrent displacement, defining stiffness as the slope of the linear
      portion of the force-displacement curve. Repeated measures analysis of variance
      with Bonferroni-adjusted post hoc comparisons determined whether stiffness
      differed between neck positions. RESULTS: There was a significant difference in
      cervical spine stiffness between different neck positions (F((1.6,38.0)) = 16.6,
      P < 0.001). Stiffness was least in extension with a mean of 3.09 N/mm (95% CI
      2.59, 3.58) followed by neutral (3.94, 95% CI 3.49, 4.39), and then flexion
      (4.32, 95% CI 3.96, 4.69). CONCLUSION: When assessing cervical spine stiffness,
      neck position should be standardised to ensure maximal reliability and utility of
      stiffness judgments.

PMID- 22651964
TI  - Calcium bodies of Titanethes albus (Crustacea: Isopoda): molt-related structural
      dynamics and calcified matrix-associated bacteria.
AB  - Crustaceans form a variety of calcium deposits in which they store calcium
      necessary for the mineralization of their exoskeletons. Calcium bodies, organs
      containing large amounts of calcium, have been reported in some terrestrial
      isopod crustaceans, but have not yet been extensively studied. We analyzed the
      architecture of these organs during the molt cycle in the isopod Titanethes
      albus. Two pairs of calcium bodies are positioned ventrolaterally in posterior
      pereonites of T. albus. Individual organs are epithelial sacs that contain
      material arranged in concentric layers delimited by thin laminae. As demonstrated
      by electron microscopy and fluorescence in situ hybridization, abundant bacteria
      are present within the calcium bodies. Regardless of the molt cycle stage,
      crystalline concretions are present in the central areas of the calcium bodies.
      Energy dispersive X-ray spectrometry of the concretions demonstrated that they
      are composed predominantly of calcium and phosphorus and selected area electron
      diffraction indicated the presence of hydroxyapatite. In molting animals, a
      glassy layer of mineralized matrix is formed between the envelope and the
      outermost lamina of the calcium body. This layer consists of an amorphous calcium
      mineral which contains less phosphorus than the central concretions and is
      resorbed after molt. Since changes in the mineralized matrix are synchronized
      with the molt cycle, the calcium bodies likely function as a storage compartment
      that complements sternal deposits as a source of calcium for the mineralization
      of the exoskeleton. Bacteria associated with the mineralized matrix of calcium
      bodies are evidently involved in calcium dynamics.

PMID- 22651965
TI  - Diffuse type gastric carcinoma presenting as giant gastric folds: lessons learned
      from six miss diagnosed cases.
AB  - Hyperplastic gastropathy is a rare condition characterized by giant gastric
      folds. There are numerous causes of giant gastric folds included benign diseases
      (Menetrier's disease, pseudolymphoma and lymphocytic gastritis) and malignant
      diseases (gastric carcinoma, lymphoma and Zollinger-Ellison syndrome). Six
      gastric carcinoma presenting as giant gastric folds were described. Lessons
      learned from six miss diagnosed cases and how to improve the accuracy of
      diagnosis were elucidated. Moreover, we propose a hypothesis that in diffuse type
      gastric carcinoma gastric cancer, which manifested with thickness of gastric
      folds, there must be some media which is released by cancer cells to stimulate
      superficial mucosa layer benign cells proliferation, instead of malignant cells
      infiltrating directly.

PMID- 22651963
TI  - High-throughput characterization of intrinsic disorder in proteins from the
      Protein Structure Initiative.
AB  - The identification of intrinsically disordered proteins (IDPs) among the targets
      that fail to form satisfactory crystal structures in the Protein Structure
      Initiative represents a key to reducing the costs and time for determining three
      dimensional structures of proteins. To help in this endeavor, several Protein
      Structure Initiative Centers were asked to send samples of both crystallizable
      proteins and proteins that failed to crystallize. The abundance of intrinsic
      disorder in these proteins was evaluated via computational analysis using
      predictors of natural disordered regions (PONDR(r)) and the potential cleavage
      sites and corresponding fragments were determined. Then, the target proteins were
      analyzed for intrinsic disorder by their resistance to limited proteolysis. The
      rates of tryptic digestion of sample target proteins were compared to those of
      lysozyme/myoglobin, apomyoglobin, and alpha-casein as standards of ordered,
      partially disordered and completely disordered proteins, respectively. At the
      next stage, the protein samples were subjected to both far-UV and near-UV
      circular dichroism (CD) analysis. For most of the samples, a good agreement
      between CD data, predictions of disorder and the rates of limited tryptic
      digestion was established. Further experimentation is being performed on a
      smaller subset of these samples in order to obtain more detailed information on
      the ordered/disordered nature of the proteins.

PMID- 22651966
TI  - Quantum dots as nano plug-in's for efficient NADH resonance energy routing.
AB  - The routing of fluorescent signals from NADH to quantum dots (QDs) has been a
      subject of extensive research for FRET based applications. In the present study,
      the spectral cross talk of NAD(+)/NADH with QDs was used to monitor the reaction
      of NAD(+)-dependent dehydrogenase enzyme. CdTe QD may undergo dipolar interaction
      with NADH as a result of broad spectral absorption due to multiple excitonic
      states resulting from quantum confinement effects. Thus, non-radiative energy
      transfer can take place from NADH to CdTe QD enhancing QDs fluorescence. Energy
      routing assay of NADH-QD was applied for detection of formaldehyde as a model
      analyte in the range 1000-0.01 ng/mL by the proposed technique. We observed
      proportionate quenching of CdTe QD fluorescence by NAD(+) and enhancement in the
      presence of NADH formed by various concentrations of enzyme (0.028-0.4 U). Hence,
      it was possible to detect formaldehyde in the range 1000-0.01 ng/mL with a limit
      of detection (LOD) at 0.01 ng/mL and regression coefficient R(2)=0.9982.
      Therefore, a unique optical sensor was developed for the detection of the
      formaldehyde in sensitive level based on the above mechanism. This method can be
      used to follow the activity of NAD(+)-dependent enzymes and detection of
      dehydrogenases in general.

PMID- 22651967
TI  - Signal amplification architecture for electrochemical aptasensor based on network
      like thiocyanuric acid/gold nanoparticle/ssDNA.
AB  - In this work, we described signal amplification architecture for electronic
      aptamer-based sensor (E-AB), which is applicable to a wide range of aptamers.
      Herein, we only take lysozyme as the representative sensing target. The
      amplification method was based on the network of thiocyanuric acid (TCA)/gold
      nanoparticles (AuNPs) modified with ssDNA. The binding event can be detected by a
      decrease in the integrated charge of the surface-bound [Ru(NH(3))(6)](3+) which
      electrostatically absorbed onto the negatively charged phosphate backbones of
      DNA. In the presence of target molecules, a large amount of TCA/AuNP/ssDNA
      network associated with [Ru(NH(3))(6)](3+) would be removed from the electrode
      surface, leading to a significant decrease of redox current. Cyclic voltammetry
      (CV) signals of [Ru(NH(3))(6)](3+) provides quantitative measures of the
      concentrations of lysozyme, with a linear calibration ranging from 5 pM to 1 nM
      and a detection limit is 0.1 pM. The detection limit of the proposed sensor is
      one order of magnitude and three orders of magnitude more sensitive than the
      detection limits in the absence of TCA (5 pM) and in the absence of
      TCA/AuNP/ssDNA network (0.5 nM). This amplification method is promising for broad
      potential application in clinic assay and various protein analysis.

PMID- 22651968
TI  - An ascorbic acid amperometric sensor using over-oxidized polypyrrole and
      palladium nanoparticles composites.
AB  - We constructed a highly responsive ascorbic acid (AA) sensor utilizing over
      oxidized polypyrrole (OPPy) and Palladium nanoparticles (PdNPs) composites (OPPy
      PdNPs). In the presence of PdNPs, polypyrrole (PPy) was coated on a gold (Au)
      electrode through cyclic voltammetry (CV) and over-oxidized at a fixed potential
      in NaOH solution. The PdNPs were characterized using ultraviolet-visible (UV-vis)
      spectrum and transmission electron microscopy (TEM). The surface of OPPy-PdNPs on
      the Au electrode was investigated using field-emission scanning electron
      microscopy (FE-SEM). Results revealed that the OPPy-PdNPs-modified Au electrode
      (OPPy-PdNPs/Au) has the capacity to catalyze the oxidation of AA by lowering its
      oxidation potential to 0 V. The OPPy-PdNPs/Au electrode exhibited 2 different
      linear concentration ranges. In the low concentration range (1-520 MUM), OPPy
      PdNPs/Au exhibited a direct linear relation with current responses and had high
      sensitivity (570 MUA mM(-1)cm(-2)) and a high correlation coefficient (0.995). In
      contrast, in the higher concentration range (120-1600 MUM), the relationship
      between current responses and concentration of AA can be represented by a two
      parameter sigmoidal equation. In addition, the sensor exhibited a short response
      time (less than 2s) and a very low limit of detection of 1 MUM. The
      electrochemical AA sensor constructed in this study was simple, inexpensive,
      reproducible, sensitive, and resistant to interference. Thus, the proposed sensor
      has great potential for detecting AA in complex biosystems and can be applied in
      various fields, particularly neuroscience.

PMID- 22651969
TI  - A novel sensor based on electrochemical polymerization of diglycolic acid for
      determination of acetaminophen.
AB  - Diglycolic acid (DA) polymer was coated on glassy carbon (GC) electrode by cyclic
      voltammetry (CV) technique for the first time. The electrochemical performances
      of the modified electrode were investigated by CV and electrochemical impedance
      (EIS). The obtained electrode showed an excellent electrocatalytic activity for
      the oxidation of acetaminophen (ACOP). A couple of well-defined reversible
      electrochemical redox peaks were observed on the ploy(DA)/GC electrode in ACOP
      solution. Compared with bare GC electrode, the oxidation peak potential of ACOP
      on ploy(DA)/GC electrode moved from 0.289 V to 0.220 V. Meanwhile, the oxidation
      peak current was much higher on the modified electrode than that on the bare GC
      electrode, indicating DA polymer modified electrode possessed excellent
      performance for the oxidation of ACOP. This kind of capability of the modified
      electrode can be enlisted for the highly sensitive and selective determination of
      ACOP. Under the optimized conditions, a wide linear range from 2 * 10(-8) to 5.0
      * 10(-4)M with a correlation coefficient 0.9995 was obtained. The detection limit
      was 6.7 * 10(-9)M (at the ratio of signal to noise, S/N=3:1). The modified
      electrode also exhibited very good stability and reproducibility for the
      detection of ACOP. The established method was applied to the determination of
      ACOP in samples. An average recovery of 100.1% was achieved. These results
      indicated that this method was reliable for determining ACOP.

PMID- 22651970
TI  - A microfluidic-based electrochemical biochip for label-free diffusion-restricted
      DNA hybridization analysis.
AB  - DNA hybridization detection in microfluidic devices can reduce sample volumes,
      processing times, and can be integrated with other measurements. However, as
      device footprints decrease and their complexity increase, the signal-to-noise
      ratio in these systems also decreases and the sensitivity is thereby compromised.
      Device miniaturization produces distinct properties and phenomena with greater
      influence at the micro-scale than at the macro-scale. Here, a diffusion
      restriction model was applied to a miniaturized biochip nanovolume reactor to
      accurately characterize DNA hybridization events that contribute to shifts in
      both charge transfer resistance and diffusional resistance. These effects are
      shown to play a significant role in electrochemical impedance spectroscopy (EIS)
      analyses at these length scales. Our highly functional microfluidic biosensor
      enables the detection of ssDNA targets selectively, with a calculated detection
      limit of 3.8 nM, and cross-reactivity of 13% following 20 min incubation with the
      target. This new biosensing approach can be further modeled and tested
      elucidating diffusion behavior in miniaturized devices and improving the
      performance of biosensors.

PMID- 22651971
TI  - Trends in the use of cytoreductive nephrectomy in the United States.
AB  - BACKGROUND: Two randomized trials published in 2001 established CyNx for patients
      with metastatic renal carcinoma (mRCC) as a treatment standard in the cytokine
      era. However, first-line systemic therapy for mRCC changed in 2005 with FDA
      approval of VEGFR TKIs. We evaluated the patterns of use of CyNx from 2000 to
      2008. MATERIALS AND METHODS: The National Cancer Database was queried for
      patients diagnosed with mRCC. Patients who underwent CyNx were identified and
      were further categorized by pre-VEGFR versus VEGFR TKI era, race, insurance
      status, and hospital. For these subcategories, prevalence ratios (PRs) were
      generated using the proportion of patients with mRCC undergoing CyNx versus those
      not undergoing CyNx. RESULTS: Of the 47,417 patients (pts) identified with mRCC,
      the prevalence of cytoreductive nephrectomy increased 3% each year from 2000 to
      2005 (P < .0001), then decreased 3% each year from 2005 to 2008 (P = .0048), with
      a significant difference between the eras (0.97 vs. 1.025; P < .0001). Black and
      Hispanic pts were less likely than Caucasian pts to undergo CyNx. Pts with
      Medicaid, Medicare, and no insurance were less likely than pts with private
      insurance to undergo CyNx. Pts diagnosed at community hospitals were
      significantly less likely than pts at teaching hospitals to undergo CyNx.
      CONCLUSION: The use of CyNx has declined in the VEGFR-TKI era. In addition,
      racial and socioeconomic disparities exist in the use of CyNx. The results of
      pending randomized trials evaluating the role of CyNx in the VEGFR-TKI era are
      awaited to optimize use of this modality and address potential disparities.

PMID- 22651972
TI  - Informed consent forms fail to reflect best practice.

PMID- 22651974
TI  - Bioassays for evaluation of medical products derived from bacterial toxins.
AB  - Bioassays play central role in evaluation of biological products and those
      derived from bacterial toxins often rely exclusively on in vivo models for
      assurance of safety and potency. This chapter reviews existing regulatory
      approved methods designed to provide information on potency and safety of complex
      biological medicines with an insight into strategies considered for alternative
      procedures.

PMID- 22651975
TI  - Learning from the past: historical aspects of bacterial toxins as
      pharmaceuticals.
AB  - Botulinum neurotoxins are the most poisonous substances known to humankind, but
      also are the bacterial toxins most frequently used as pharmaceuticals to benefit
      humans. The discovery of botulinum toxins and development into a useful drug is
      unique and fascinating, dating back to the early 19th century, when Justinus
      Kerner first recognized that botulism was caused by a biological toxin and
      suggested its use for medicinal purposes. This was translated into reality in
      1980, when Alan Scott for the first time used the toxins to successfully treat
      strabismus. Now a subset of botulinum toxins are widely used for cosmetic
      applications, treatment of various movement disorders, pain and many other
      syndromes, and further developments using other botulinum toxins or recombinant
      molecules engineered from subdomains are promising.

PMID- 22651973
TI  - Shaping cities for health: complexity and the planning of urban environments in
      the 21st century.

PMID- 22651976
TI  - Pseudosarcoma - massive localized lymphoedema in morbidly obese - a rare entity:
      Case report.
AB  - INTRODUCTION: Massive localized lymphoedema (MLL) first described in 1998 by
      Farshid and Weiss. Usually MLL present like huge pedunculated mass and appear
      like sarcoma hence called Pseudosarcoma. Morbid obesity is a growing epidemic in
      our society. Morbid obesity is usually associated with hypertension, Diabetes
      mellitus, dermatological complications like Acanthosis nigricans, skin tags, leg
      ulcers, edema, lymphoedema, plantar hyperkeratosis and massive localized
      lymphoedema (MLL) is one of the complications of morbid obesity. Pseudosarcoma is
      due to derangement of lymphatic channels secondary to excessive deposition of
      adipose tissue. PRESENTATION OF CASE: We report a patient afflicted with this
      unique disorder presented with huge mass arising from monspubis in morbidly obese
      individual with body mass index (BMI) 55. DISCUSSION: Massive localized
      lymphedema presenting like pseudosarcoma in morbidly obese individuals is rare.
      Awareness of this disease is essential to avoid misdiagnosis as soft tissue
      neoplasm. It is a term used to describe a benign over growth of
      lymhoproliferative tissue in morbidly obese patients. Because of its size
      patients have difficult to do daily activities. Histopathologically characterized
      by dilated lymphatic channels with fibrotic and edematous tissue, without
      evidence of malignancy. Patient seeks treatment only if there is huge swelling
      causing discomfort, complications like excoriation, wound break down occur. The
      treatment of choice is complete excision. CONCLUSION: Surgical treatment is
      effective if done along with bariatric surgery. Functional rehabilitation was
      achieved. No recurrence was observed within the follow up period of twenty months
      and BMI was reduced to 28.

PMID- 22651977
TI  - The role of the CNA Pain Assessment Tool (CPAT) in the pain management of nursing
      home residents with dementia.
AB  - Implementation and testing of the CPAT in two hundred fifteen dementia residents
      of three regional skilled nursing facilities. To examine the effect of
      incorporating the CPAT into an AMDA long-term care pain management clinical
      practice guideline on nursing home residents with dementia. To evaluate changes
      in CPAT scores after treatment for pain. A non-randomized pre and post
      intervention design was used. Main outcome measures of the number of falls,
      episodes of distressed behavior and rates of antipsychotic usage were compared
      pre and post CPAT/AMDA guideline implementation. CPAT score changes were
      calculated after pain management. Falls and verbally aggressive behavior were
      reduced post intervention but did not achieve statistical significance.
      Antipsychotic usage declined significantly post intervention. CPAT scores
      declined significantly after treatment for pain. The implementation of a
      CPAT/AMDA guideline in skilled nursing facilities may reduce falls, verbally
      aggressive behaviors and antipsychotic usage in residents with dementia. The CPAT
      is useful in evaluating the effects of pain treatment in nursing home residents
      with dementia.

PMID- 22651978
TI  - Nursing strategies for promoting and maintaining function among community-living
      older adults: the CAPABLE intervention.
AB  - Although many programs aim to help older adults age in place, few target both the
      home environment and individual physical function. We present an
      interprofessional intervention called CAPABLE-Community Aging in Place: Advancing
      Better Living for Elders. CAPABLE's innovative approach incorporates a nurse,
      occupational therapist (OT), and handyman to address both individual and
      environmental factors that contribute to disability. The nurse component of
      CAPABLE addresses key barriers to functional independence such as pain,
      depression, strength and balance, medication management, and poor communication
      with the primary care provider. This article focuses primarily on the nursing
      aspect of the intervention and how it interrelates with the content and processes
      of the OT and handyman.

PMID- 22651979
TI  - Role of nerve growth factor (NGF) and its receptors in folliculogenesis.
AB  - Summary Nerve growth factor (NGF) is a prototype member of the neurotrophins
      family and has important functions in the maintenance of viability and
      proliferation of neuronal and non-neuronal cells, such as certain ovarian cells.
      The present review highlights the role of NGF and its receptors on ovarian
      follicle development. NGF initiates its multiple actions through binding to two
      classes of receptors: the high affinity receptor tyrosine kinase A (TrkA) and the
      low-affinity receptor p75. Different intracytoplasmic signalling pathways may be
      activated through binding to NGF due to variation in the receptors. The TrkA
      receptor activates predominantly phosphatidylinositol-3-kinase (PI3K) and
      mitogenic activated protein kinase (MAPK) to promote cell survival and
      proliferation. The activation of the phospholipase type Cgamma (PLCgamma)
      pathway, which results in the production of diacylglycerol (DAG) and inositol
      triphosphate (IP3), culminates in the release of calcium from the
      intracytoplasmic cellular stocks. However, the details of activation through p75
      receptor are less well known. Expression of NGF and its receptors is localized in
      ovarian cells (oocyte, granulosa, theca and interstitial cells) from several
      species, which suggests that NGF and its receptors may regulate some ovarian
      functions such as follicular survival or development. Thus, the use of NGF in
      culture medium for ovarian follicles may be of critical importance for
      researchers who want to promote follicular development in vitro in the future.

PMID- 22651980
TI  - Microvascular porcine model for the optimization of vascularized composite tissue
      transplantation.
AB  - BACKGROUND: Devastating extremity injuries are prevalent but most often
      survivable on the modern battlefield. The complexity of these injuries requires
      advanced methods of reconstruction. This study is designed to validate the
      feasibility of gracilis myocutaneous flap transplantation via microvascular free
      tissue transfer in a porcine model. This model will facilitate study of
      autotransplant physiology as well as vascularized composite allotransplantation
      as an evolving method for reconstructing previously nonreconstructable injuries.
      MATERIAL AND METHODS: A donor gracilis myocutaneous flap is procured from
      Yorkshire swine. The right external carotid artery and internal jugular vein are
      prepared as the recipient axis for microvascular anastomoses. Group 1 undergoes
      immediate microvascular anastomosis with resultant 1-h ischemic period. Group 2
      undergoes delayed anastomosis with 3-h ischemic period. Markers of ischemia
      reperfusion injury are evaluated after anastomosis and on postoperative days 1,
      2, 7, and 14. RESULTS: A novel porcine model for microvascular composite tissue
      transplantation is demonstrated. Ischemia period-dependent elevations in
      circulating biomarkers (lactate dehydrogenase [LDH], creatine kinase [CK], and
      aspartate transaminase [AST]) demonstrate the effects of prolonged ischemia. Both
      groups showed marked LDH elevation without significant statistical intergroup
      difference (P=0.250). The difference in CK and AST levels at 24h showed strong
      significance (P<0.0001). CONCLUSIONS: A novel method of vascularized gracilis
      myocutaneous flap transplantation was validated in the Yorkshire swine. Assays
      for skeletal muscle tissue injury (LDH, CK, and AST) showed ischemia period
      dependent response providing assessment of ischemia-reperfusion injury at the
      cellular level. Subsequent studies will evaluate agents that mitigate ischemia
      reperfusion injury and transition these findings to potentiate vascularized
      composite allotransplantation.

PMID- 22651981
TI  - Differential gender- and species-specific formation of aneurysms using a novel
      method of inducing abdominal aortic aneurysms.
AB  - BACKGROUND: The objective of this study was to test a novel model of inducing
      abdominal aortic aneurysms (AAAs) in different mouse strains and genders.
      MATERIALS AND METHODS: Male and female C57BL/6 and B6129 mice (n = 5 per group)
      underwent periaortic dissection and porcine pancreatic elastase (30 MUL) or
      inactivated elastase application (5 min) to the aorta. Aortic measurements were
      taken on days 0 and 14. Aortic samples were analyzed for histology and zymography
      for matrix metalloproteinase (MMP) activity. Comparison statistics were performed
      using unpaired t-test. RESULTS: AAA phenotype (50% aortic increase) occurred in
      external elastase-treated males (100%) and females (90%). No control animals
      developed AAAs. The aortic diameter was larger in C57BL/6 and B6129 elastase
      treated versus control males (P = 0.0028 and P < 0.0001, respectively) and
      females (P < 0.0001 and P = 0.0458, respectively). Histology verified phenotype
      via disrupted internal elastic laminae. Macrophage counts in elastase-treated
      animals were >6-fold higher than in controls (all groups significant). MMP9
      activity was greater in elastase-treated males and females in C57BL/6 (P =
      0.0031, P = 0.0004) and B6129 (P = 0.025, P = 0.2) mice; MMP2 activity was
      greater in C57BL/6 versus B6129 male elastase-treated mice. CONCLUSIONS: This
      rodent model produced AAAs in both genders and strains of mice. This model is
      simple, has little variability, and occurs in the infrarenal aorta,
      substantiating the external elastase model for future studies.

PMID- 22651982
TI  - Development of children's internalising and externalising problems from infancy
      to five years of age.
AB  - OBJECTIVE: Mental health problems are an international public health issue
      affecting a substantial proportion of youth. This study aimed to identify groups
      of young children exhibiting distinct internalising and externalising symptom
      trajectories across early childhood compared to existing norms. Linear regression
      then identified child, parenting and family predictors from infancy in the
      development of internalising and externalising behaviours at age 5 years. METHOD:
      This consisted of a follow-up of 5-year-old children from a longitudinal,
      population-based study with earlier surveys having been completed by primary
      caregivers when the children were aged 7, 12, 18, 24 and 36 months. Five hundred
      5-year-olds (68% retention) were included from 733 children recruited at age 6-7
      months from routine well-child appointments across six socio-economically diverse
      government areas in Victoria, Australia. Mothers then completed a further
      questionnaire when their children reached 5 years of age, repeating the
      instruments included in previous waves. The primary outcomes were the Child
      Behavior Checklist (CBCL), 1.5-5 internalising and externalising symptoms (T
      scores in relation to norms) and behaviours (raw scores). RESULTS: Across early
      childhood, three distinct profiles for each of the internalising and
      externalising symptoms (T-scores) were identified and compared to CBCL norms.
      Around 20% of this Australian child population exhibited consistently elevated
      symptoms for each problem. Regarding aetiology, longitudinally the strongest
      predictors of internalising behaviours at 5 years of age were harsh discipline,
      maternal stress, having no older siblings, single parenthood and maternal
      substance misuse. The strongest predictors of externalising behaviours at 5 years
      of age were male sex, harsh discipline and maternal stress. The predictors
      explained 22% of the variation in internalising behaviours and 24% of the
      variation in externalising behaviours at 5 years. CONCLUSIONS: Starting as early
      as the toddler period, effective population approaches to preventing mental
      health problems are needed. Randomised trials of preventive interventions focused
      on improving parenting practices and reducing maternal stress are under way.

PMID- 22651984
TI  - Bacterial actin homolog ParM: arguments for an apolar, antiparallel double helix.
AB  - The bacterial actin homolog ParM has always been modeled as a polar filament,
      comprising two parallel helical strands, like actin itself. I present arguments
      here that ParM may be an apolar filament, in which the two helical strands are
      antiparallel.

PMID- 22651985
TI  - Toxicity of clopidogrel and ticlopidine on human myeloid progenitor cells:
      importance of metabolites.
AB  - Ticlopidine and clopidogrel are thienopyridine derivatives used for inhibition of
      platelet aggregation. Not only hepatotoxicity, but also bone marrow toxicity may
      limit their use. Aims of the study were to find out whether non-metabolized drug
      and/or metabolites are responsible for myelotoxicity and whether the inactive
      clopidogrel metabolite clopidogrel carboxylate contributes to myelotoxicity. We
      used myeloid progenitor cells isolated from human umbilical cord blood in a
      colony-forming unit assay to assess cytotoxicity. Degradation of clopidogrel,
      clopidogrel carboxylate or ticlopidine (studied at 10 and 100 MUM) was monitored
      using LC/MS. Clopidogrel and ticlopidine were both dose-dependently cytotoxic
      starting at 10 MUM. This was not the case for the major clopidogrel metabolite
      clopidogrel carboxylate. Pre-incubation with recombinant human CYP3A4 not only
      caused degradation of clopidogrel and ticlopidine, but also increased
      cytotoxicity. In contrast, clopidogrel carboxylate was not metabolized by
      recombinant human CYP3A4. Pre-incubation with freshly isolated human granulocytes
      was not only associated with a myeloperoxidase-dependent degradation of
      clopidogrel, clopidogrel carboxylate and ticlopidine, but also with dose
      dependent cytotoxicity of these compounds starting at 10 MUM. In conclusion, both
      non-metabolized clopidogrel and ticlopidine as well as metabolites of these
      compounds are toxic towards myeloid progenitor cells. Taking exposure data in
      humans into account, the myelotoxic element of clopidogrel therapy is likely to
      be secondary to the formation of metabolites from clopidogrel carboxylate by
      myeloperoxidase. Concerning ticlopidine, both the parent compound and metabolites
      formed by myeloperoxidase may be myelotoxic in vivo. The molecular mechanisms of
      cytotoxicity have to be investigated in further studies.

PMID- 22651983
TI  - A phylogenetic analysis of normal modes evolution in enzymes and its relationship
      to enzyme function.
AB  - Since the dynamic nature of protein structures is essential for enzymatic
      function, it is expected that functional evolution can be inferred from the
      changes in protein dynamics. However, dynamics can also diverge neutrally with
      sequence substitution between enzymes without changes of function. In this study,
      a phylogenetic approach is implemented to explore the relationship between enzyme
      dynamics and function through evolutionary history. Protein dynamics are
      described by normal mode analysis based on a simplified harmonic potential force
      field applied to the reduced C(alpha) representation of the protein structure
      while enzymatic function is described by Enzyme Commission numbers. Similarity of
      the binding pocket dynamics at each branch of the protein family's phylogeny was
      analyzed in two ways: (1) explicitly by quantifying the normal mode overlap
      calculated for the reconstructed ancestral proteins at each end and (2)
      implicitly using a diffusion model to obtain the reconstructed lineage-specific
      changes in the normal modes. Both explicit and implicit ancestral reconstruction
      identified generally faster rates of change in dynamics compared with the
      expected change from neutral evolution at the branches of potential functional
      divergences for the alpha-amylase, D-isomer-specific 2-hydroxyacid dehydrogenase,
      and copper-containing amine oxidase protein families. Normal mode analysis added
      additional information over just comparing the RMSD of static structures.
      However, the branch-specific changes were not statistically significant compared
      to background function-independent neutral rates of change of dynamic properties
      and blind application of the analysis would not enable prediction of changes in
      enzyme specificity.

PMID- 22651987
TI  - Anticholinergics in the era of atypical antipsychotics: short-term or long-term
      treatment?
AB  - Anticholinergic agents are usually prescribed to prevent or treat antipsychotic
      induced extrapyramidal symptoms. Their long-term benefits are questionable and
      they carry diverse adverse effects, including cognitive impairment and worsening
      of tardive dyskinesia. This literature review explores the impact of
      anticholinergic medication discontinuation on movement disorders, cognition and
      psychopathology in patients receiving antipsychotics. Medline, Embase and
      PsycInfo were searched from 1950 to July 2011 using "cessation /withdrawal
      /discontinuation /stopping" with "anticholinergic*" or "antiparkinson*" and
      "neuroleptic*" or "antipsychotic*". Additional articles were obtained by
      searching the bibliographies of relevant references. Earlier studies of
      anticholinergic agent discontinuation in patients receiving first-generation
      antipsychotics reported relapse rates of extrapyramidal symptoms between 4% and
      80%, reflecting the heterogeneity of the studies. Two recent studies of patients
      prescribed second-generation antipsychotics obtained relapse rates of 4% and 33%.
      Some studies suggest improvement in tardive dyskinesia with cessation of
      anticholinergics. Four studies examined the effects of anticholinergic agent
      discontinuation on cognition and all observed an improvement post
      discontinuation. Changes in symptoms of schizophrenia with anticholinergic
      discontinuation are conflicting, with more recent studies suggesting an
      improvement. Given their questionable benefit with continued use, clinicians
      should consider a gradual withdrawal of anticholinergic agents in stable patients
      receiving antipsychotics.

PMID- 22651986
TI  - One-year outcomes of telephone case monitoring for patients with substance use
      disorder.
AB  - BACKGROUND: Many patients treated for substance use disorder (SUD) do not achieve
      lasting recovery from a single episode of treatment and require continuing care.
      The current randomized clinical trial investigated whether in-person continuing
      care as usual (CCAU) following intensive outpatient SUD treatment leads to better
      SUD outcomes when compared with telephone case monitoring (TCM). METHOD: This
      study randomized 667 intensive SUD outpatients to telephone case monitoring
      versus face-to-face continuing care as usual at two sites. Patients completed
      data at baseline, 3 and 12months with telephone interviews. Data of interest
      include self-report of substance use, psychiatric symptoms, quality of life, and
      treatment satisfaction. We also evaluated potential interaction effects for
      distance to VA provider, SUD severity, and presence of co-morbid psychiatric
      disorder. RESULTS: Participants randomized to the telephone case monitoring
      condition substantially engaged with face-to-face continuing care resulting in
      cross-over contamination. We addressed this issue by using randomization as an
      instrumental variable to evaluate the impact of telephone case monitoring
      (contamination adjusted, intent to treat analysis). Instrumental variable
      analyses indicated significant benefit of telephone case monitoring for drug and
      alcohol percent days abstinent and psychiatric symptom outcomes at 3-months
      follow-up, but not at 12-month follow-up. No interaction analyses were
      significant. DISCUSSION: Participants receiving telephone case monitoring
      achieved better short term outcomes in terms of substance use and psychiatric
      symptoms. The "on treatment" effects suggests the need for future studies to
      investigate consumer (patient) perspectives on the optimal duration of telephone
      case monitoring and use of alternative monitoring methods such as text messaging.

PMID- 22651988
TI  - A flicker change blindness task employing eye tracking reveals an association
      with levels of craving not consumption.
AB  - We investigated attentional biases with a flicker paradigm, examining the
      proportion of alcohol relative to neutral changes detected. Furthermore, we
      examined how measures of the participants initial orienting of attention and of
      their maintained attention relate to levels of alcohol consumption and subjective
      craving in social drinkers. The eye movements of 58 participants (24 male) were
      monitored whilst they completed a flicker-induced change blindness task using
      both simple stimuli and real world scenes, with both an alcohol and neutral
      change competing for detection. When examined in terms of consumption levels, we
      observed that heavier social drinkers detected a higher proportion of alcohol
      related changes in real world scenes only. However, we also observed that levels
      of craving were not indicative of levels of consumption in social drinkers.
      Furthermore, also in real world scenes only, higher cravers detected a greater
      proportion of alcohol related changes compared to lower cravers, and were also
      quicker to initially fixate on alcohol related stimuli. Thus we conclude that
      processing biases in the orienting of attention to alcohol related stimuli were
      demonstrated in higher craving compared to lower craving social users in real
      world scenes. However, this was not related to the level of consumption as would
      be expected. These results highlight various methodological and conceptual issues
      to be considered in future research.

PMID- 22651989
TI  - Molecular cloning and functional analysis of a voltage-gated potassium channel in
      lymphocytes from sea perch, Lateolabrax japonicus.
AB  - Voltage-gated potassium (Kv) channels on cell plasma membrane play an important
      role in both excitable cells and non-excitable cells and Kv1 subfamily is most
      extensively studied channel in mammalian cells. Recently, this potassium channel
      was reported to control processes inside mammalian T lymphocytes such as cell
      proliferation and volume regulation. Little is known about Kv1 channels in fish.
      We have postulated the presence of such a channel in lymphocytes and speculated
      its potential role in immunoregulation in fish. Employing specific primers and
      RNA template, we cloned a segment of a novel gene from sea perch blood sample and
      subsequently obtained a full cDNA sequence using RACE approach. Bioinformatic
      analysis revealed structural and phylogenetic characteristics of a novel Kv
      channel gene, designated as spKv1.3, which exhibits homologous domains to the
      members of Kv1.3 family, but it differs notably from some other members of that
      family at the carboxyl terminus. Full-length of spKv1.3 cDNA is 2152 bp with a
      1440 bp open reading frame encoding a protein of 480 amino acids. SpKv1.3 gene is
      expressed in all of the tested organs and tissues of sea perch. To assess the
      postulated immune function of spKv1.3, we stimulated lymphocytes with LPS and/or
      channel blocker 4-AP. Expression levels of messenger RNA (mRNA) of spKv1.3 under
      stimulation conditions were measured by quantitative RT-PCR. The results showed
      that LPS can motivate the up-regulation of spKv1.3 expression significantly.
      Interestingly, we found for the first time that 4-AP with LPS can also increase
      the spKv1.3 mRNA expression levels in time course. Although 4-AP could block
      potassium channels physically, we speculated that its effect on blockage of
      potassium channel may start up an alternative mechanism which feed back and evoke
      the spKv1.3 mRNA expression.

PMID- 22651990
TI  - Intrathecal treatment of cerebral vasospasm.
AB  - Treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH)
      remains a major therapeutic challenge. Systemic drug administration is the
      current treatment of choice, but patients often do not respond beneficially to
      this approach. Intrathecal (IT) drug administration has several anatomic and
      pharmacodynamic advantages over conventional systemic treatment of cerebral
      vasospasm. We reviewed the most recent literature describing IT administration of
      several drugs to treat aneurysm-induced SAH and cerebral vasospasm, including 16
      clinical trials using IT fibrinolytic agents and 10 trials using several IT
      vasodilators. We evaluated the safety and effectiveness of these trials but made
      no attempt to perform a meta-analysis using these data. IT drug administration of
      fibrinolytic agents and vasodilators caused lysis of the subarachnoid clot burden
      and diminished cerebral vasospasm, respectively. The studies reviewed reported a
      wide range of drug doses, intervals between aneurysm hemorrhage and initiation of
      treatment, success of clot dissolution, and degree of vasodilation of vessels in
      vasospasm. Treatment of vasospasm by IT drug administration is safe and largely
      effective after the aneurysm has been secured. Our findings indicate that IT
      treatment effectively delivers a higher drug concentration to vessels in
      vasospasm with minimal systemic effects. Drugs administered by this route are
      reported to lyse subarachnoid clots, attenuate cerebral vasospasm, improve
      clinical outcomes, and decrease the incidence of hydrocephalus. With greater
      understanding of drug pharmacodynamics, the IT route of drug administration may
      provide a rational, alternative approach to treating aneurysm-induced cerebral
      vasospasm. 

PMID- 22651991
TI  - Streamlining genomes: toward the generation of simplified and stabilized
      microbial systems.
AB  - At the junction between systems and synthetic biology, genome streamlining
      provides a solid foundation both for increased understanding of cellular
      circuitry, and for the tailoring of microbial chassis towards innovative
      biotechnological applications. Iterative genomic deletions (targeted and random)
      helps to generate simplified, stabilized and predictable genomes, whereas
      multiplexing genome engineering reveals a broad functional genetic diversity. The
      decrease in oligo and gene synthesis costs promises effective combinatorial tools
      for the generation of chassis based on streamlined and tractable genomes. Here we
      review recent progresses in streamlining genomes through recombineering
      techniques aiming to generate insights into cellular mechanisms and responses
      towards the design and assembly of streamlined genome chassis together with new
      cellular modules in diverse biotechnological applications.

PMID- 22651992
TI  - Phase I and II biotransformation enzymes and polycyclic aromatic hydrocarbons in
      the Mediterranean mussel (Mytilus galloprovincialis, Lamarck, 1819) collected in
      front of an oil refinery.
AB  - The aim of the present study was to investigate the responses of phase I and II
      biotransformation enzymes and levels of PAHs in the Mediterranean mussel (Mytilus
      galloprovincialis, Lamarck, 1819) collected from three sites at different
      distance from an oil refinery. Phase I enzyme activities as NAD(P)H-cyt c red,
      NADH ferry red, B(a)PMO and phase II as UDPGT, GST were measured in digestive
      gland while 16 PAHs (US-EPA) in whole soft tissue. An added value to the data
      obtained in the present study rely on the RDA analysis which showed close
      correlations between PAHs levels and phase I enzyme activities in mussels
      collected in front of the refinery. And again a significant spatial correlation
      between B(a)P levels and NADPH-cyt c red activities was observed using linear
      models. No differences among sites for B(a)PMO and phase II GST activities were
      observed, while the application of UDPGT as biomarkers requires further
      investigation.

PMID- 22651993
TI  - A reduced scoring system for the Clock Drawing Test using a population-based
      sample.
AB  - BACKGROUND: Many scoring systems exist for clock drawing task variants, which are
      common dementia screening measures, but all have been derived from clinical
      samples. This study evaluates and combines errors from two published scoring
      systems for the Clock Drawing Test (CDT), the Lessig and Tuokko methods, in order
      to create a simple yet optimal scoring procedure to screen for dementia using a
      Canadian population-based sample. METHODS: Clock-drawings from 356 participants
      (80 with dementia, 276 healthy controls) from the Canadian Study on Health and
      Aging were analyzed using logistic regression and Receiver Operating
      Characteristic curves to determine a new, simplified, population-based CDT
      scoring system. The new Jouk scoring method was then compared to other commonly
      used systems (e.g. Shulman, Tuokko, Watson, Wolf-Klein). RESULTS: The Jouk
      scoring system reduced the Lessig system even further to include five critical
      errors: missing numbers, repeated numbers, number orientation, extra marks, and
      number distance, and produced a sensitivity of 81% and a specificity of 68% with
      a cut-off score of one error. With regard to other traditionally used scoring
      methods, the Jouk procedure had one of the most balanced
      sensitivities/specificities when using a population-based sample. CONCLUSIONS:
      The results from this study improve our current state of knowledge concerning the
      CDT by validating the simplified scoring system proposed by Lessig and her
      colleagues in a more representative sample to mimic conditions a general
      clinician or researcher will encounter when working among a wide-ranging
      population and not a dementia/memory clinic. The Jouk CDT scoring system provides
      further evidence in support of a simple and reliable dementia-screening tool that
      can be used by clinicians and researchers alike.

PMID- 22651994
TI  - Application of nanoLC-MS/MS to the shotgun proteomic analysis of the nematocyst
      proteins from jellyfish Stomolophus meleagris.
AB  - The nematocyst proteins of jellyfish Stomolophus meleagris, a complicated
      mixture, contain many important bioactive molecules. In present study, to gain
      comprehensive insight into the protein component and search some novel bioactive
      molecules in the nematocyst proteins, shotgun proteomic analysis of the
      nematocyst proteins was carried out by nano liquid chromatography tandem mass
      spectrometry (nanoLC-MS/MS) for the first time. Digested peptides of the
      nematocyst proteins were analyzed by nanoLC-MS/MS and all MS/MS spectra were then
      automatically searched by the SEQUEST program. A total of 181 proteins had been
      identified, with the molecular weight ranging from 5268.06 to 843,487.57 and the
      pI from 4.49 to 11.39. Bioinformatic analysis was also applied to better
      understand the identified proteins. In the gene ontology (GO) annotation, all the
      identified proteins were classified into 13, 9 and 7 groups according to
      biological process, cellular component and molecular function, respectively.
      Pathways analysis of the identified proteins was conducted with 33 corresponding
      pathways found. On the basis of pathways analysis, we also constructed the gene
      network to analyze the relationship of those genes each other, which contained
      enzyme-enzyme relation, protein-protein interaction and gene expression
      interaction.

PMID- 22651995
TI  - Simultaneous determination of dextromethorphan, dextrorphan and doxylamine in
      human plasma by HPLC coupled to electrospray ionization tandem mass spectrometry:
      application to a pharmacokinetic study.
AB  - In the present study, a fast, sensitive and robust method to quantify
      dextromethorphan, dextrorphan and doxylamine in human plasma using deuterated
      internal standards (IS) is described. The analytes and the IS were extracted from
      plasma by a liquid-liquid extraction (LLE) using diethyl-ether/hexane (80/20,
      v/v). Extracted samples were analyzed by high performance liquid chromatography
      coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS).
      Chromatographic separation was performed by pumping the mobile phase
      (acetonitrile/water/formic acid (90/9/1, v/v/v) during 4.0min at a flow-rate of
      1.5 mL min-1 into a Phenomenex Gemini(r) C18, 5 MUm analytical column (150 * 4.6
      mm i.d.). The calibration curve was linear over the range from 0.2 to 200 ng mL-1
      for dextromethorphan and doxylamine and 0.05 to 10 ng mL-1 for dextrorphan. The
      intra-batch precision and accuracy (%CV) of the method ranged from 2.5 to 9.5%,
      and 88.9 to 105.1%, respectively. Method inter-batch precision (%CV) and accuracy
      ranged from 6.7 to 10.3%, and 92.2 to 107.1%, respectively. The run-time was for
      4 min. The analytical procedure herein described was used to assess the
      pharmacokinetics of dextromethorphan, dextrorphan and doxylamine in healthy
      volunteers after a single oral dose of a formulation containing 30 mg of
      dextromethorphan hydrobromide and 12.5mg of doxylamine succinate. The method has
      high sensitivity, specificity and allows high throughput analysis required for a
      pharmacokinetic study.

PMID- 22651996
TI  - Imaging microglial activation and glucose consumption in a mouse model of
      Alzheimer's disease.
AB  - In Alzheimer's disease (AD), persistent microglial activation as sign of chronic
      neuroinflammation contributes to disease progression. Our study aimed to in vivo
      visualize and quantify microglial activation in 13- to 15-month-old AD mice using
      [(11)C]-(R)-PK11195 and positron emission tomography (PET). We attempted to
      modulate neuroinflammation by subjecting the animals to an anti-inflammatory
      treatment with pioglitazone (5-weeks' treatment, 5-week wash-out period). [(11)C]
      (R)-PK11195 distribution volume values in AD mice were significantly higher
      compared with control mice after the wash-out period at 15 months, which was
      supported by immunohistochemistry data. However, [(11)C]-(R)-PK11195 MUPET could
      not demonstrate genotype- or treatment-dependent differences in the 13- to 14
      month-old animals, suggesting that microglial activation in AD mice at this age
      and disease stage is too mild to be detected by this imaging method.

PMID- 22651997
TI  - [Breast augmentation by Poly Implant Protheses silicone implants: retrospective
      study about 99 patients. Rupture analysis and management].
AB  - BACKGROUND: Breast augmentation is one of the most frequent intervention in
      plastic surgery. In March 2010, the Afssaps has withdrawn from the market all the
      Poly Implant Protheses (PIP) silicone implants, the authors report a
      retrospective study of 99 patients who had breast augmentation by PIP implants.
      The aims of this work are to evaluate the ruptures observed with these implants
      and to propose a management. METHODS: We included in the study 99 patients and
      192 silicone gel implants. The interventions were performed between 2005 and
      2010. On 192 implants, 184 had a textured surface and eight a smooth one.
      According to the latest recommendations from the Afssaps, all patients had a
      clinical examination and an ultrasonography looking for rupture signs. MRI was
      performed in case of doubt. RESULTS: We found 23 ruptured implants: 18
      intracapsular and five extracapsular ruptures, involving 17 patients. We also
      found 28 patients with axillary lymphadenopathy and eight patients with
      locoregional silicone spread. Finally, we found that 35 patients had chronic
      breast pains. CONCLUSION: Given our results, it seems reasonable to withdraw all
      the PIP silicone breast implants.

PMID- 22651998
TI  - [French dental surgeons are struggling to keep the right to use filler on the
      face].

PMID- 22651999
TI  - Acute ascending aortic dissection 41 years after mustard procedure.

PMID- 22652000
TI  - CASE 5--2012: incidentally detected patent foramen ovale in a patient undergoing
      aortic valve replacement: to close or not to close?

PMID- 22652001
TI  - Emergency subclavian vein cannulation through a modified supraclavicular approach
      in a patient with a halo traction device.

PMID- 22652002
TI  - Early extubation in adults undergoing surgery for congenital heart disease.
AB  - OBJECTIVES: Early extubation in adults undergoing surgery for congenital heart
      disease has not been described. The authors report their experience with
      extubation in the operating room (OR), including factors associated with the
      decision to defer extubation to a later time. DESIGN: A retrospective chart
      review. SETTING: A tertiary-care teaching hospital. PARTICIPANTS: This study
      included adults undergoing surgery for congenital heart disease using
      cardiopulmonary bypass. Exclusion criteria were as follows: preoperative
      mechanical ventilation, age >70 years, inotrope score >20 after surgery, and
      surgical risk (Risk Adjustment for Congenital Heart Surgery [RACHS] score >=4).
      INTERVENTIONS: A stepwise logistic regression model was used to test for the
      independent influence of the various factors on extubation in the OR.
      MEASUREMENTS AND MAIN RESULTS: Sixty-seven patients (age 18-59 years, median = 32
      years) were included. Overall, 79% of patients were extubated in the OR. The
      RACHS score was the strongest predictor of deferring extubation (RACHS 3 v 1 or
      2: odds ratio = 16.7; 95% confidence interval, 3.3-84.2; p = 0.0006). Further
      exploration of the high-risk group (RACHS 3) showed that 75% of the RACHS 3
      patients with a body mass index <25 were extubated compared with only 20% of
      patients who had a body mass index >=25 (p = 0.01). Other factors included in the
      analysis did not contribute any additional independent information. CONCLUSIONS:
      Extubation of adult patients in the OR after surgery for congenital heart disease
      is feasible in most cases. Surgical risk (RACHS score) and body mass index
      predict the decision for OR extubation in this patient population.

PMID- 22652003
TI  - Mutation-selection balance and mixed mating with asexual reproduction.
AB  - The effects of asexual reproduction on both the number of deleterious mutations
      per gamete and the mean fitness under mutation-selection balance are
      investigated. We use two simulation models, considering both finite and infinite
      populations. The two models incorporate asexual reproduction with varying levels
      of outcrossing and selfing, degrees of dominance and selection coefficients. The
      values for mean fitness and number of deleterious mutations per gamete are
      compared within and among finite and infinite populations to identify the effect
      of asexual reproduction on levels of load, and how asexual reproduction may
      interact with genetic drift (population size). Increasing asexual reproduction
      resulted in an increase in mean fitness and a decrease in the average number of
      deleterious mutations per gamete for both nearly recessive and additive alleles
      in both the infinite and finite simulations. Increased mean fitness with
      increasing asexuality is possibly due to two interacting forces: a greater
      opportunity for selection to act on heterozygous versus homozygous mutations and
      the shielding of a proportion of the population from meiotic mutations due to
      asexual reproduction. The results found here highlight the need to consider
      asexual reproduction along with mixed mating in models of genetic load and
      mutation-selection balance.

PMID- 22652004
TI  - Ventricular HCN channels decrease the repolarization reserve in the hypertrophic
      heart.
AB  - AIMS: Cardiac hypertrophy is accompanied by reprogramming of gene expression,
      where the altered expression of ion channels decreases electrical stability and
      increases the risk of life-threatening arrhythmias. However, the underlying
      mechanisms are not fully understood. Here, we analysed the role of the
      depolarizing current I(f) which has been hypothesized to contribute to
      arrhythmogenesis in the hypertrophied ventricle. METHODS AND RESULTS: We used
      transverse aortic constriction in mice to induce ventricular hypertrophy. This
      resulted in an increased number of I(f) positive ventricular myocytes as well as
      a strongly enhanced and accelerated I(f) when compared with controls. Of the four
      HCN (hyperpolarization-activated cyclic nucleotide-gated channels) isoforms
      mediating I(f), HCN2 and HCN4 were the predominantly expressed subunits in
      healthy as well as hypertrophied hearts. Unexpectedly, only the HCN1 transcript
      was significantly upregulated in response to hypertrophy. However, the combined
      deletion of HCN2 and HCN4 disrupted ventricular I(f) completely. The lack of I(f)
      in hypertrophic double-knockouts resulted in a strong attenuation of pro
      arrhythmogenic parameters characteristically observed in hypertrophic hearts. In
      particular, prolongation of the action potential was significantly decreased and
      lengthening of the QT interval was reduced. CONCLUSIONS: We suggest that the
      strongly increased HCN channel activity in hypertrophied myocytes prolongs the
      repolarization of the ventricular action potential and thereby may increase the
      arrhythmogenic potential. Our results provide for the first time a direct link
      between an upregulation of ventricular I(f) and a diminished repolarization
      reserve in cardiac hypertrophy.

PMID- 22652005
TI  - Arterial endothelial cells: still the craftsmen of regenerated endothelium.
AB  - For more than a decade, a prevailing hypothesis in research related to arterial
      disease has been that circulating endothelial progenitor cells (EPCs) provide
      protection by their innate ability to replace dysfunctional or damaged
      endothelium. This paradigm has led to extensive investigation of EPCs in the hope
      of finding therapeutic targets to control their homing and differentiation.
      However, from the very beginning, the nomenclature and the phenotype of EPCs have
      been subject to controversy and there are currently no specific markers that can
      unambiguously identify these cells. Moreover, many of the initial observations
      that EPCs differentiate to endothelial cells in the course of arterial disease
      have been criticized for methodological problems. The present review discusses
      the contrasting experimental evidence as to the role of EPCs in contributing to
      relining of the endothelium and highlights some of the methodological pitfalls
      and terminological ambiguities that confuse the field.

PMID- 22652006
TI  - Perfluorooctanoic acid exposure is associated with elevated homocysteine and
      hypertension in US adults.
AB  - OBJECTIVE: To investigate the association between serum perfluorooctanoic acid
      (PFOA) concentration and cardiovascular disease, as measured by homocysteine
      level and blood pressure in a representative sample of US adults. METHODS: A
      cross-sectional study of 2934 adults (>=20 years) who participated in the 2003
      2004 and 2005-2006 National Health and Nutrition Examination Survey and had
      detectable levels of PFOA in their serum. The health effects analysed as
      potentially associated with PFOA exposure included homocysteine level and blood
      pressure. RESULTS: The geometric mean value (95% CI) of the study participants'
      serum PFOA concentration was 4.00 MUg/l (95% CI 3.86 to 4.13). The homocysteine
      and systolic blood pressure were shown to increase significantly with an increase
      in the log-transformed serum PFOA concentration, after adjusting for potential
      confounding variables. Adjusted ORs comparing participants at the 80th versus the
      20th percentiles were 2.62 for hypertension (95% CI 2.09 to 3.14), and a positive
      association was also evident in models based on quartiles or based on restricted
      cubic splines. CONCLUSION: These findings suggest that background exposure to
      PFOA may continue a risk factor for the development of cardiovascular diseases.

PMID- 22652007
TI  - Root coverage stability of the subepithelial connective tissue graft and guided
      tissue regeneration: a 30-month follow-up clinical trial.
AB  - OBJECTIVES: The aim of this study was to compare the long-term clinical effects
      produced by subepithelial connective tissue graft (SCTG) and guided tissue
      regeneration combined with demineralized freeze-dried bone allograft (GTR-DFDBA)
      in the treatment of gingival recessions in a 30-month follow-up clinical trial.
      METHODS: Twenty-four defects were treated in 12 patients who presented canine or
      pre-molar Miller class I and/or II bilateral gingival recessions. GTR-DFDBA and
      SCTG treatments were performed in a randomized selection in a split-mouth design.
      The clinical measurements included root coverage (RC), gingival recession (GR),
      probing depth (PD), clinical attachment level (CAL) and keratinized tissue width
      (KTW). These clinical parameters were evaluated at baseline and after 6, 18 and
      30months post-surgery. RESULTS: The changes in RC, GR, PD and CAL did not show
      significant differences between groups (p>0.05). Both procedures promoted similar
      RC (GTR-DFDBA: 87% and SCTG: 95.5%) and similar reduction in GR (GTR-DFDBA:
      3.25mm and SCTG: 3.9mm), PD (GTR-DFDBA: 1.6mm and SCTG: 1.2mm) and CAL (GTR
      DFDBA: 4.9mm and SCTG: 5.0mm). The increase in KTW was significantly higher
      (p=0.02) in the SCTG group (3.5mm) than in the GTR-DFDBA group (2.4mm).
      CONCLUSIONS: Both techniques for treatment of gingival recession (SCTG and GTR
      DFDBA) lead to favourable and long-term stable results, but SCTG promoted a more
      favourable increase in keratinized tissue.

PMID- 22652008
TI  - Levels, sources and potential human health risks of organic pollutants in urban
      soils.
AB  - Urban soil quality may be severely affected by PAH and PCB contamination,
      impairing environmental and human health. A comprehensive study was conducted in
      two contrasting Portuguese urban areas (Lisbon and Viseu) in order to assess the
      levels of these contaminants and potential risks to human health, to identify
      sources and study their behavior in soils. The concentrations of PAHs and PCBs
      were related to the size of the city. The concentrations found in the larger city
      (Lisbon) were similar to other urban areas. Differences between profiles of the
      two urban areas were observed for both groups of contaminants, which could be
      attributed to differences of sources or climate. Lisbon seems to be affected by
      nearby sources (traffic, industry and incineration processes) whereas in the
      smaller city atmospheric transport may be playing an important role. Cluster
      analysis revealed that PAHs and PCBs were associated with anthropogenic toxic
      elements (Cu, Pb, Zn and Hg in Lisbon; Pb and Hg in Viseu), therefore reflecting
      common sources. It was also found that organic carbon was an important factor for
      PAHs and high chlorinated PCB retention in soils. The incremental probability of
      developing cancer over lifetime, based on a reasonable maximum exposure to PAHs
      present in Lisbon residential soils, was 9.0 * 10(-6) and 2.4 * 10(-6) for an
      occupational exposure, both slightly higher than the target risk of 1 * 10(-6).
      Similarly, the mutagenic risk of PAHs in Lisbon was 3.3 * 10(-5) for residential
      soils and 1.8 * 10(-6) in recreational areas.

PMID- 22652009
TI  - Dermal exposure assessment of pesticide use: the case of sprayers in potato farms
      in the Colombian highlands.
AB  - Quantifying dermal exposure to pesticides in farming systems in developing
      countries is of special interest for the estimation of potential health risks,
      especially when there is a lack of occupational hygiene regulations. In this
      paper we present the results of a dermal exposure assessment for the potato
      farming system in the highlands of Colombia, where farmers apply pesticides with
      hand pressure sprayers without any personal protective equipment. The fractioning
      of the pesticide, in terms of potential and actual dermal exposure, was
      determined via the whole-body dosimetry methodology, using the tracer uranine as
      pesticide surrogate, and luminescence spectrometry as analytical method. We
      assessed the three activities involved in pesticide management: preparation,
      application, and cleaning; analyzed three types of nozzles: one with a standard
      discharge and two modified by farmers to increase the discharge; and derived the
      protection factor given by work clothing. Our results suggest that to reduce the
      health risk, three aspects have to be considered: (i) avoiding the modification
      of nozzles, which affects the droplet size spectrum and increases the level of
      dermal exposure; (ii) using adequate work clothing made of thick fabrics,
      especially on the upper body parts; and (iii) cleaning properly the tank sprayer
      before the application activity.

PMID- 22652010
TI  - Soot particles at an elevated site in eastern China during the passage of a
      strong cyclone.
AB  - Atmospheric particles larger than 0.2 MUm were collected at the top of Mt. Tai
      (36.25 degrees N, 117.10 degrees E, 1534 m a.s.l.) in eastern China in May 2008
      during the passage of a strong cyclone. The particles were analyzed with electron
      microscopes and characterized by morphology, equivalent diameter and elemental
      composition. Soot particles with coating (coated soot particles) and those
      without apparent coating (naked soot particles) were predominant in the diameter
      range smaller than 0.6 MUm in all samples. The number-size distribution of the
      relative abundance of naked soot particles in the prefrontal air was similar to
      that in the postfrontal air and their size modes were around 0.2-0.3 MUm.
      However, the distribution of inclusions of coated soot particles showed a mode in
      the range of 0.1-0.3 MUm. The coating degree of coated soot particles, which was
      defined by the ratio of the diameter of inclusion to the diameter of particle
      body, showed a mode around 0.5 with the range of 0.3-0.6. These results indicate
      that the status of soot particles in the prefrontal and postfrontal air was
      similar although air pollution levels were dramatically different. In addition,
      the relative abundance of accumulation mode particles increased with the decrease
      of soot particles after the front passage.

PMID- 22652011
TI  - An investigation on physicians' acceptance of hospital information systems: a
      case study.
AB  - PURPOSE: Information technology is used to support a wide range of highly
      specified healthcare tasks and services. There is, therefore, a need to
      understand the factors affecting the acceptance of this technology by healthcare
      professionals. Physicians are key providers of healthcare services and are among
      the principal users of hospital information systems. Their acceptance of hospital
      information systems is hence of great significance when evaluating the success of
      those systems. METHOD: The survey methodology was employed to targeted physicians
      in the selected case hospital for investigating factors affecting physicians'
      acceptance of hospital information systems. A total of 202 questionnaires were
      sent out, with 124 completed copies returned, indicating a valid response rate of
      61.4%. We used structural equation modeling to analyze the data. RESULTS: The
      results indicated that top management support (gamma=0.431, p<0.001) had a
      significant impact on perceived usefulness. Project team competency (gamma=0.381,
      p<0.001) and system quality (gamma=0.369, p<0.001) had a significant impact on
      physicians' perceived ease of use of hospital information systems. Physicians'
      perceptions of the usefulness (beta=0.132, p<0.05, R(2)=0.296) and ease of use
      (beta=0.952, p<0.001, R(2)=0.784) of hospital information systems had a
      significant impact on the acceptance of the systems, accounting for 81.4% of
      total explained variance. CONCLUSIONS: Through the understanding of the
      identified critical factors affecting physicians' HIS acceptance, the planners
      and managers should ensure that hospital information systems to be introduced
      into a hospital are useful and ease to use. Effort should be focuses on providing
      sufficient top management support, selecting qualified project team members, and
      delivering higher system quality in addressing physicians' clinical needs. Thus,
      our research results can help planners and managers understand key considerations
      affecting HIS development and use, and may be used as a reference for system
      design, development and implementation.

PMID- 22652012
TI  - SMS reminders improve adherence to oral medication in type 2 diabetes patients
      who are real time electronically monitored.
AB  - BACKGROUND: Poor adherence to oral antidiabetics has a negative influence on
      glycaemic control in type 2 diabetes patients. Real Time Medication Monitoring
      (RTMM) combines real time monitoring of patients' medication use with SMS
      reminders sent only if patients forget their medication, aiming to improve
      adherence. This study aimed to investigate the effect of these SMS reminders on
      adherence to oral antidiabetics in patients using RTMM and investigate patients'
      experiences with RTMM. METHODS: Data were collected in a RCT involving 104 type 2
      diabetes patients with suboptimal adherence to oral antidiabetics. Fifty-six
      patients were randomised to receive SMS reminders if they forgot their
      medication, 48 patients received no reminders. Primary outcome measure was
      adherence to oral antidiabetics registered with RTMM, measured as: (1) days
      without dosing; (2) missed doses; (3) doses taken within predefined standardized
      time windows. Patients' experiences were assessed with written questionnaires.
      RESULTS: Over the six-month study period, patients receiving SMS reminders took
      significantly more doses within predefined time windows than patients receiving
      no reminders: 50% vs. 39% within a 1-h window (p=0.003) up to 81% vs. 70% within
      a 4-h window (p=0.007). Reminded patients tended to miss doses less frequently
      than patients not reminded (15% vs. 19%, p=0.065). Days without dosing were not
      significantly different between the groups. The majority of patients reported
      positive experiences with RTMM and SMS reminders. CONCLUSION: RTMM with SMS
      reminders improves adherence of type 2 diabetes patients, especially the
      precision with which patients follow their prescribed regimen, and is well
      accepted by patients. TRIAL REGISTRATION: Netherlands Trial Register NTR1882.

PMID- 22652014
TI  - The impact of relationships, motivations, and meanings on dementia caregiving
      outcomes.
AB  - BACKGROUND: Numerous theoretical models have been developed to explore how
      caregiving can impact on caregiving outcomes. However, limited attention has been
      given to the effects of caregivers' motivations for providing care, the meaning
      they find in caregiving, and the nature of their relationship with the care
      recipient. The current study explored the associations between intrinsic and
      extrinsic motivations, ability to find meaning in caregiving, and pre-caregiving
      and current relationship quality, and the way in which these variables interact
      to influence caregiving outcomes. METHODS: This was a cross-sectional
      questionnaire study, in which the respondents were 447 caregivers of people with
      dementia who were in receipt of a specialist nursing service. RESULTS: The
      results showed that intrinsic motivations, meaning, and pre-caregiving and
      current relationship quality were significantly related to each other, while
      extrinsic motivations were only related to intrinsic motivations and meaning. All
      these factors were significantly related to caregiving outcomes as measured by
      caregiver burden, role captivity, and competence. CONCLUSIONS: Based on these
      findings, it is recommended that interventions aimed at reducing caregiving
      stress should take into account the impact of the quality of the relationship and
      the caregivers' motivations for providing care. More longitudinal research is
      needed to explore how meanings, motivations, and relationship quality change over
      the caregiving career.

PMID- 22652013
TI  - Overfeeding and underfeeding have detrimental effects on oocyte quality measured
      by in vitro fertilization and early embryonic development in sheep.
AB  - To determine effects of maternal diet on in vitro fertilization (IVF) and early
      embryonic development, ewes (n = 48) were divided into control, overfed (ad
      libitum feeding), and underfed (60% of control) nutritional planes for 8 wk
      before oocyte collection. Follicular development was induced by twice-daily
      injections of FSH on days 13 and 14 of the estrous cycle, and ovaries and blood
      samples were collected on day 15 of the estrous cycle. During the 8-wk
      experiment, for control ewes BW and BCS did not change, but for overfed ewes mean
      (+/- SEM) BW and BCS increased (11.8 +/- 1.1 kg and 2.0 +/- 0.1, respectively)
      and for underfed ewes decreased (14.2 +/- 0.9 kg and 0.7 +/- 0.1, respectively).
      The number of follicles was determined; oocytes were collected and subjected to
      in vitro maturation and fertilization. After IVF, developing embryos were
      evaluated throughout the 8-d culture period. The proportion of cleaved oocytes
      after IVF and developing morula and blastocyst were less (P < 0.0001) in overfed
      and underfed ewes than in control ewes. However, number of visible follicles,
      total number of oocytes, number of healthy oocytes, and percentage of healthy
      oocytes were similar for control, overfed, and underfed ewes. Serum insulin
      concentration was greater (P < 0.05) in overfed ewes than in underfed ewes,
      estradiol 17-beta (E(2)) concentration was greater (P < 0.05) in underfed ewes
      than in overfed ewes, but triiodothyronine (T(3)) and thyroxine (T(4))
      concentrations were similar in all treatment groups. These data show that
      inadequate feeding has a negative effect on oocyte quality which results in lower
      oocyte cleavage after IVF and morula and blastocyst formation; overfeeding
      increased serum insulin and underfeeding increased serum E(2) but not T(3) or
      T(4). These data emphasize the importance of diet for reproductive and metabolic
      functions. Furthermore, the mechanisms through which enhanced or decreased energy
      in diet affect oocyte quality and serum insulin and E(2) concentrations remain to
      be elucidated.

PMID- 22652015
TI  - [Ectopic retroperitoneal thyroid gland].
AB  - The presence of subdiaphragmatic thyroid tissue is a very rare finding. We
      reviewed the literature and found only 15 published cases. The most appropriate
      management of this entity has not been established, but surgical removal is
      common to exclude malignancy. We present the case of a 76-year-old woman with an
      ectopic mesenteric thyroid gland forming a retroperitoneal mass that was
      surgically removed. Outcome was favorable.

PMID- 22652016
TI  - [Linezolid, coagulase-negative Staphylococcus and the problem of resistances].

PMID- 22652017
TI  - [Life-threatening hemoptysis: a continuous multidisciplinary challenge].

PMID- 22652018
TI  - [Advances in the pathophysiology and management of infections in the acute phase
      of stroke].
AB  - Infection in the acute phase of stroke has been identified as an independent
      predictor of poor outcome, both in the short and intermediate term. Various
      factors raising the risk of developing an infection (exposure to multiple
      pathogens, disruption of the protective function of the mucous membranes and a
      state of relative immunosuppression) coexist during the acute phase of stroke.
      Several risk factors have been identified for their development (especially
      increasing age and stroke severity). It has been proposed that infection
      contributes to a worse prognosis through different mechanisms, notably the
      development of an inflammatory response to brain tissue (with a potential to add
      secondary damage to that caused by the ischemic insult). Clinical trials
      evaluating the prophylactic and early administration of antibiotics to reduce the
      incidence of infection in the acute phase of stroke have yielded inconsistent
      results. Immunomodulating strategies, which may provide therapeutic alternatives
      in the future, are currently being evaluated.

PMID- 22652020
TI  - Simultaneous intracranial EEG-fMRI in humans: protocol considerations and data
      quality.
AB  - We have recently performed simultaneous intracranial EEG and fMRI recordings
      (icEEG-fMRI) in patients with epilepsy. In this technical note, we examine
      limited thermometric data for potential electrode heating during our protocol and
      found that heating was <=0.1  degrees C in-vitro at least 10 fold less than in
      vivo limits. We quantify EEG quality, which can be degraded by MRI scanner
      induced artefacts, and fMRI image (gradient echo echo-planar imaging: GE-EPI)
      signal quality around the electrodes, which can be degraded by electrode
      interactions with B1 (radiofrequency) and B0 (static) magnetic fields. We
      recorded EEG outside and within the MRI scanner with and without scanning. EEG
      quality was largely preserved during scanning and in particular heartbeat-related
      artefacts were small compared to epileptic events. To assess the GE-EPI signal
      reduction around the electrodes, we compared image signal intensity along paths
      into the brain normal to its surface originating from the individual platinum
      iridium electrode contacts. GE-EPI images were obtained at 1.5 T with an echo
      time (TE) of 40 ms and repetition time (TR) of 3000 ms and a slice thickness of
      2.5 mm. We found that GE-EPI signal intensity reduction was confined to a 10 mm
      radius and that it was reduced on average by less than 50% at 5mm from the
      electrode contacts. The GE-EPI image signal reduction also varied with electrode
      orientation relative to the MRI scanner axes; in particular, cortical grid
      contacts with a normal along the scanner's main magnetic field (B(0)) axis have
      higher artefact levels relative to those with a normal perpendicular to the z
      axis. This suggests that the artefacts were predominantly susceptibility-related
      rather than due to B1 interactions. This information can be used to guide
      interpretation of results of icEEG-fMRI experiments proximal to the electrodes,
      and to optimise artefact reduction strategies.

PMID- 22652019
TI  - Hippocampal angiogenesis and progenitor cell proliferation are increased with
      antidepressant use in major depression.
AB  - BACKGROUND: Adult neurogenesis is coupled to angiogenesis in neurogenic niches in
      the dentate gyrus (DG) and increased by antidepressants in rodents. We
      hypothesized that, in major depressive disorder (MDD), antidepressants increase
      neural progenitor cells (NPCs) and capillaries in the human DG. METHODS: Neural
      progenitor cells and capillaries, detected on hippocampal sections by
      immunohistochemistry for neural stem cell protein, were quantified by stereology
      in matched MDDs (untreated, n = 12), MDD treated with selective serotonin
      reuptake inhibitors (MDD*SSRI, n = 6) or tricyclic antidepressants (MDD*TCA, n =
      6), and nonpsychiatric control subjects (n = 12), all confirmed by psychological
      autopsy. RESULTS: The MDD*SSRI had a larger capillary area and more NPCs versus
      MDDs (p = .034 and p = .008, respectively) and control subjects (p = .010 and p =
      .002, respectively) in the whole DG, more NPCs in the anterior (pes, p = .042)
      and central (midbody, p = .004) DG, and greater capillary area in the pes (p =
      .002) and midbody (p = .021). The NPC number and capillary area correlated
      positively in the whole sample (R2 = .454, p < .001) and in treated subjects (R2
      = .749, p = .001). We found no NPCs or antidepressant-related angiogenesis in CA1
      and parahippocampal gyrus. The DG volume correlated positively with NPC number (p
      = .004) and capillary area (p < .001) and differed between groups in whole
      hippocampus (p = .013) and midbody (p = .036). Age negatively correlated with NPC
      number (p = .042), capillary area (p = .037), and bifurcations (p = .030). No
      gender effect was detected. CONCLUSIONS: Antidepressants increase human
      hippocampal NPCs and angiogenesis selectively in the anterior and mid DG. These
      results raise the possibility of a causal relationship between angiogenesis and
      neurogenesis, as seen in other proliferating tissues, and support their possible
      role in the mechanism of action of antidepressants.

PMID- 22652022
TI  - Quantitative theory of driven nonlinear brain dynamics.
AB  - Strong periodic stimuli such as bright flashing lights evoke nonlinear responses
      in the brain and interact nonlinearly with ongoing cortical activity, but the
      underlying mechanisms for these phenomena are poorly understood at present. The
      dominant features of these experimentally observed dynamics are reproduced by the
      dynamics of a quantitative neural field model subject to periodic drive. Model
      power spectra over a range of drive frequencies show agreement with multiple
      features of experimental measurements, exhibiting nonlinear effects including
      entrainment over a range of frequencies around the natural alpha frequency
      f(alpha), subharmonic entrainment near 2f(alpha), and harmonic generation.
      Further analysis of the driven dynamics as a function of the drive parameters
      reveals rich nonlinear dynamics that is predicted to be observable in future
      experiments at high drive amplitude, including period doubling, bistable phase
      locking, hysteresis, wave mixing, and chaos indicated by positive Lyapunov
      exponents. Moreover, photosensitive seizures are predicted for physiologically
      realistic model parameters yielding bistability between healthy and seizure
      dynamics. These results demonstrate the applicability of neural field models to
      the new regime of periodically driven nonlinear dynamics, enabling interpretation
      of experimental data in terms of specific generating mechanisms and providing new
      tests of the theory.

PMID- 22652021
TI  - Anisotropic partial volume CSF modeling for EEG source localization.
AB  - Electromagnetic source localization (ESL) provides non-invasive evaluation of
      brain electrical activity for neurology research and clinical evaluation of
      neurological disorders such as epilepsy. Accurate ESL results are dependent upon
      the use of patient specific models of bioelectric conductivity. While the effects
      of anisotropic conductivities in the skull and white matter have been previously
      studied, little attention has been paid to the accurate modeling of the highly
      conductive cerebrospinal fluid (CSF) region. This study examines the effect that
      partial volume errors in CSF segmentations have upon the ESL bioelectric model.
      These errors arise when segmenting sulcal channels whose widths are similar to
      the resolution of the magnetic resonance (MR) images used for segmentation, as
      some voxels containing both CSF and gray matter cannot be definitively assigned a
      single label. These problems, particularly prevalent in pediatric populations,
      make voxelwise segmentation of CSF compartments a difficult problem. Given the
      high conductivity of CSF, errors in modeling this region may result in large
      errors in the bioelectric model. We introduce here a new approach for using
      estimates of partial volume fractions in the construction of patient specific
      bioelectric models. In regions where partial volume errors are expected, we use a
      layered gray matter-CSF model to construct equivalent anisotropic conductivity
      tensors. This allows us to account for the inhomogeneity of the tissue within
      each voxel. Using this approach, we are able to reduce the error in the resulting
      bioelectric models, as evaluated against a known high resolution model.
      Additionally, this model permits us to evaluate the effects of sulci modeling
      errors and quantify the mean error as a function of the change in sulci width.
      Our results suggest that both under and over-estimation of the CSF region leads
      to significant errors in the bioelectric model. While a model with fixed partial
      volume fraction is able to reduce this error, we see the largest improvement when
      using voxel specific partial volume estimates. Our cross-model analyses suggest
      that an approximately linear relationship exists between sulci error and the
      error in the resulting bioelectric model. Given the difficulty of accurately
      segmenting narrow sulcal channels, this suggests that our approach may be capable
      of improving the accuracy of patient specific bioelectric models by several
      percent, while introducing only minimal additional computational requirements.

PMID- 22652023
TI  - Gas-filled microbubble-mediated delivery of antigen and the induction of immune
      responses.
AB  - The use of well characterized recombinant or purified protein antigens (Ag) for
      vaccination is of interest for safety reasons and in the case where inactivated
      pathogens are not available (cancer, allergy). However it requires the addition
      of adjuvants such as Ag carrier or immune stimulators to potentiate their
      immunogenicity. In this study, we demonstrated that gas-filled microbubbles (MB)
      can serve as an efficient Ag delivery system to promote phagocytosis of the model
      Ag ovalbumin (OVA) without the need of ultrasound application. Once internalized
      by DC, OVA was processed and presented to both CD4 and CD8 T cells in vitro; such
      observations were coupled with the capacity of MB to activate DC. In vivo
      administration of MB-associated OVA in naive wild-type Balb/c mice resulted in
      the induction of OVA-specific antibody and T cell responses. Detailed
      characterization of the generated immune response demonstrated the production of
      both IgG1 and IgG2a serum antibodies, as well as the secretion of IFN-gamma and
      IL-10 by splenocytes. Interestingly, similar results were obtained with human DC
      in regards of Ag delivery and cell activation. Therefore, the data presented here
      settle the proof of principle for the further evaluation of MB-based
      immunomodulation studies.

PMID- 22652025
TI  - Family mealtimes: a contextual approach to understanding childhood obesity.
AB  - There has been a growing interest in the role that shared family mealtimes may
      play in promoting the health and well-being of children. Families that regularly
      eat their main meal together four or more times a week are more likely to have
      children who do better in school, are of average weight, less likely to use drugs
      and alcohol at an early age, and consume more fruits and vegetables. The mere
      fact that families eat together does not address the process by which shared
      family mealtimes may protect children from unhealthy weight gain. Just as there
      is no simple explanation for the rising rates of obesity, the link between shared
      family mealtimes and childhood obesity is a complex one including socioeconomic
      and cultural context. In this paper, we provide an overview of how shared family
      mealtimes are embedded in a socio-cultural context that may either support or
      derail healthy eating patterns for children and youth. Evidence from an
      observational study of 200 family mealtimes demonstrates the complex interplay
      between socio-economic factors, family mealtime behaviors, and child obesity
      status. Families who had a child of healthy weight spent more time engaged with
      each other during the meal, expressed more positive communication, and considered
      mealtimes more important and meaningful than families who had a child who was
      overweight or obese. Using a cumulative risk model, it was found that the
      combination of family level and neighborhood risk factors predicted child
      overweight status. Recommendations are made for future research directions and
      policies directed toward families living in diverse economic circumstances.

PMID- 22652024
TI  - Lipid nanoparticles for hepatic delivery of small interfering RNA.
AB  - Clinical application of small interfering RNA (siRNA) requires safe and efficient
      delivery in vivo. Here, we report the design and synthesis of lipid nanoparticles
      (LNPs) for siRNA delivery based on cationic lipids with multiple tertiary amines
      and hydrophobic linoleyl chains. LNPs incorporating the lipid containing tris(2
      aminoethyl)amine (TREN) and 3 linoleyl chains, termed TRENL3, were found to have
      exceptionally high siRNA transfection efficacy that was markedly superior to
      lipofectamine, a commercial transfection agent. In addition, inclusion of
      polyunsaturated fatty acids, such as linoleic acid and linolenic acid in the
      formulation further enhanced the siRNA delivery efficiency. TRENL3 LNPs were
      further shown to transport siRNA into the cytosol primarily via macropinocytosis
      rather than clathrin-mediated endocytosis. The new LNPs have demonstrated
      preferential uptake by the liver and hepatocellular carcinoma in mice, thereby
      leading to high siRNA gene-silencing activity. These data suggest potential
      therapeutic applications of TRENL3 mediated delivery of siRNA for liver diseases.

PMID- 22652026
TI  - Brain structure and function in chronic obstructive pulmonary disease: a
      multimodal cranial magnetic resonance imaging study.
AB  - RATIONALE: Brain pathology is a poorly understood systemic manifestation of
      chronic obstructive pulmonary disease (COPD). Imaging techniques using magnetic
      resonance (MR) diffusion tensor imaging (DTI) and resting state functional MR
      imaging (rfMRI) provide measures of white matter microstructure and gray
      functional activation, respectively. OBJECTIVES: We hypothesized that patients
      with COPD would have reduced white matter integrity and that functional
      communication between gray matter resting-state networks would be significantly
      different to control subjects. In addition, we tested whether observed
      differences related to disease severity, cerebrovascular comorbidity, and
      cognitive dysfunction. METHODS: DTI and rfMRI were acquired in stable
      nonhypoxemic patients with COPD (n = 25) and compared with age-matched control
      subjects (n = 25). Demographic, disease severity, stroke risk, and
      neuropsychologic assessments were made. MEASUREMENTS AND MAIN RESULTS: Patients
      with COPD (mean age, 68; FEV(1) 53 +/- 21% predicted) had widespread reduction in
      white matter integrity (46% of white matter tracts; P < 0.01). Six of the seven
      resting-state networks showed increased functional gray matter activation in COPD
      (P < 0.01). Differences in DTI, but not rfMRI, remained significant after
      controlling for stroke risk and smoking (P < 0.05). White matter integrity and
      gray matter activation seemed to account for difference in cognitive performance
      between patients with COPD and control subjects. CONCLUSIONS: In stable
      nonhypoxemic COPD there is reduced white matter integrity throughout the brain
      and widespread disturbance in functional activation of gray matter, which may
      contribute to cognitive dysfunction. White matter microstructural integrity but
      not gray matter functional activation is independent of smoking and
      cerebrovascular comorbidity. The mechanisms remain unclear, but may include
      cerebral small vessel disease caused by COPD.

PMID- 22652027
TI  - Malignant pleural effusion: tumor-host interactions unleashed.
AB  - Malignant pleural effusion (MPE) poses a significant clinical problem. Current
      nonetiologic management is suboptimal in terms of efficacy and safety. In light
      of recent research progress, we propose herein a new view of MPE development,
      which may rapidly translate into meaningful changes in therapeutics. In addition
      to tumor-induced impairment of pleural fluid drainage, pertinent findings point
      toward another pathway to MPE formation: a vicious loop of interactions between
      pleural-based tumor cells and the host vasculature and immune system that results
      in increased net fluid production via enhanced plasma extravasation into the
      pleural space. The ability of tumor cells to trigger this cascade likely rests on
      a specific and distinct transcriptional repertoire, which results in important
      vasoactive events in the pleural space. Although the characterization of tumor
      derived factors responsible for MPE development is in the making, an additional,
      indirect path to MPE was recently demonstrated: tumor cells recruit and co-opt
      host cells and mediators, which, in turn, amplify tumor cell-primed fluid leakage
      and impact tumor cell functions. Importantly, recent evidence suggests that the
      biologic events that culminate in clinical MPE are likely amenable to therapeutic
      inhibition and even prevention. In this perspective, the scientific basis for an
      update of current concepts of MPE formation is highlighted. Key questions for
      future research are posed. Finally, a vision for novel, effective, safe, and
      convenient treatment modalities that can be offered to outpatients with MPE is
      set forth.

PMID- 22652028
TI  - Vitamin D insufficiency and severe asthma exacerbations in Puerto Rican children.
AB  - RATIONALE: Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been
      associated with severe asthma exacerbations, but this could be explained by
      underlying racial ancestry or disease severity. Little is known about vitamin D
      and asthma in Puerto Ricans. OBJECTIVES: To examine whether vitamin D
      insufficiency is associated with severe asthma exacerbations in Puerto Rican
      children, independently of racial ancestry, atopy, and time outdoors. METHODS: A
      cross-sectional study was conducted of 560 children ages 6-14 years with (n =
      287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma
      vitamin D and estimated the percentage of African racial ancestry among
      participants using genome-wide genotypic data. We tested whether vitamin D
      insufficiency is associated with severe asthma exacerbations, lung function, or
      atopy (greater than or equal to one positive IgE to allergens) using logistic or
      linear regression. Multivariate models were adjusted for African ancestry, time
      outdoors, atopy, and other covariates. MEASUREMENTS AND MAIN RESULTS: Vitamin D
      insufficiency was common in children with (44%) and without (47%) asthma. In
      multivariate analyses, vitamin D insufficiency was associated with higher odds of
      greater than or equal to one severe asthma exacerbation in the prior year (odds
      ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.9; P = 0.001) and atopy, and
      a lower FEV(1)/FVC in cases. After stratification by atopy, the magnitude of the
      association between vitamin D insufficiency and severe exacerbations was greater
      in nonatopic (OR, 6.2; 95% CI, 2-21.6; P = 0.002) than in atopic (OR, 2; 95% CI,
      1-4.1; P = 0.04) cases. CONCLUSIONS: Vitamin D insufficiency is associated with
      severe asthma exacerbations in Puerto Rican children, independently of racial
      ancestry, atopy, or markers of disease severity or control.

PMID- 22652029
TI  - Genomic medicine and lung diseases.
AB  - The recent explosion of genomic data and technology points to opportunities to
      redefine lung diseases at the molecular level; to apply integrated genomic
      approaches to elucidate mechanisms of lung pathophysiology; and to improve early
      detection, diagnosis, and treatment of lung diseases. Research is needed to
      translate genomic discoveries into clinical applications, such as detecting
      preclinical disease, predicting patient outcomes, guiding treatment choices, and
      most of all identifying potential therapeutic targets for lung diseases. The
      Division of Lung Diseases in the National Heart, Lung, and Blood Institute
      convened a workshop, "Genomic Medicine and Lung Diseases," to discuss the
      potential for integrated genomics and systems approaches to advance 21st century
      pulmonary medicine and to evaluate the most promising opportunities for this next
      phase of genomics research to yield clinical benefit. Workshop sessions included
      (1) molecular phenotypes, molecular biomarkers, and therapeutics; (2) new
      technology and opportunity; (3) integrative genomics; (4) molecular anatomy of
      the lung; (5) novel data and information platforms; and (6) recommendations for
      exceptional research opportunities in lung genomics research.

PMID- 22652030
TI  - Interleukin 5 is protective during sepsis in an eosinophil-independent manner.
AB  - RATIONALE: The immune response in sepsis is characterized by overt immune
      dysfunction. Studies indicate immunostimulation represents a viable therapy for
      patients. One study suggests a potentially protective role for interleukin 5 (IL
      5) in sepsis; however, the loss of eosinophils in this disease presents a
      paradox. OBJECTIVES: To assess the protective and eosinophil-independent effects
      of IL-5 in sepsis. METHODS: We assessed the effects of IL-5 administration on
      survival, bacterial burden, and cytokine production after polymicrobial sepsis.
      In addition, we examined the effects on macrophage phagocytosis and survival
      using fluorescence microscopy and flow cytometry. MEASUREMENTS AND MAIN RESULTS:
      Loss of IL-5 increased mortality and tissue damage in the lung, IL-6 and IL-10
      production, and bacterial burden during sepsis. Therapeutic administration of IL
      5 improved mortality in sepsis. Interestingly, IL-5 administration resulted in
      neutrophil recruitment in vivo. IL-5 overexpression in the absence of eosinophils
      resulted in decreased mortality from sepsis and increased circulating neutrophils
      and monocytes, suggesting their importance in the protective effects of IL-5.
      Furthermore, novel data demonstrate IL-5 receptor expression on neutrophils and
      monocytes in sepsis. IL-5 augmented cytokine secretion, activation, phagocytosis,
      and survival of macrophages. Importantly, macrophage depletion before the onset
      of sepsis eliminated IL-5-mediated protection. The protective effects of IL-5
      were confirmed in humans, where IL-5 levels were elevated in patients with
      sepsis. Moreover, neutrophils and monocytes from patients expressed the IL-5
      receptor. CONCLUSIONS: Taken together, these data support a novel role for IL-5
      on noneosinophilic myeloid populations, and suggest treatment with IL-5 may be a
      viable therapy for sepsis.

PMID- 22652032
TI  - Hinfinity filtering for discrete-time genetic regulatory networks with random
      delays.
AB  - The H(infinity) filtering problem is investigated in this paper for a class of
      discrete-time genetic regulatory networks (GRNs) with random delays. The
      addressed filtering problem is to estimate the concentrations of mRNA and
      protein, and the filtering error system is modeled as a Markovian switched
      system. By using a properly constructed Lyapunov function, a sufficient condition
      is derived in terms of linear matrix inequalities (LMIs), which can guarantee
      stochastic stabilization of the filtering error system. Then, an optimization
      problem with LMIs constraints is established to design an H(infinity) filter
      which ensures an optimal H(infinity) disturbance attenuation level. Finally, an
      illustrative example is given to demonstrate the effectiveness of the proposed
      results.

PMID- 22652033
TI  - Classification of large-time behaviors in a reaction-diffusion system modeling
      diallelic selection.
AB  - We study a mathematical model from population genetics, describing a single-locus
      diallelic (A/a) selection-migration process. The model consists of a coupled
      system of three reaction-diffusion equations, one for the density of each
      genotype, posed in a bounded domain or in the whole space R(n). The genotype AA
      is advantageous, due to a smaller death rate, and the main concern is to
      determine whether or not the disadvantageous gene a is eliminated in the large
      time limit. This model was studied in the celebrated work of Aronson and
      Weinberger (1975,1977), where they derived a simplified scalar model as an
      approximation of the full system and studied the asymptotic behavior for the
      scalar model. In particular they showed that, in the fully recessive case (same
      death rate for the heterozygote and inferior homozygote), the behavior crucially
      depends on the space dimension. In a previous paper, we were able to prove that
      their results concerning the scalar model in the fully recessive case remain
      valid in a certain sense for the full system. In this paper, we reconsider the
      general case (all possible values of the death and birth rates). We succeed to
      give a complete picture of whether or not the disadvantageous gene a can survive
      as t->infinity, according to the values of the death and birth rates and of the
      space dimension. We find distinctive behaviors according to whether the
      homozygote is superior, intermediate, or inferior and, in the latter case, to
      whether the common birth rate is smaller or higher than the difference of the
      death rates of the two heterozygotes. In cases when the disadvantageous gene
      disappears, the decay rate of its frequency is estimated as well.

PMID- 22652031
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration prevents
      mediastinoscopies in the diagnosis of isolated mediastinal lymphadenopathy: a
      prospective trial.
AB  - RATIONALE: Patients with isolated mediastinal lymphadenopathy (IML) are a common
      presentation to physicians, and mediastinoscopy is traditionally considered the
      "gold standard" investigation when a pathological diagnosis is required.
      Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is
      established as an alternative to mediastinoscopy in patients with lung cancer.
      OBJECTIVE: To determine the efficacy and health care costs of EBUS-TBNA as an
      alternative initial investigation to mediastinoscopy in patients with isolated
      IML. METHODS: Prospective multicenter single-arm clinical trial of 77 consecutive
      patients with IML from 5 centers between April 2009 and March 2011. All patients
      underwent EBUS-TBNA. If EBUS-TBNA did not provide a diagnosis, then participants
      underwent mediastinoscopy. MEASUREMENTS AND MAIN RESULTS: EBUS-TBNA prevented 87%
      of mediastinoscopies (95% confidence interval [CI], 77-94%; P < 0.001) but failed
      to provide a diagnosis in 10 patients (13%), all of whom underwent
      mediastinoscopy. The sensitivity and negative predictive value of EBUS-TBNA in
      patients with IML were 92% (95% CI, 83-95%) and 40% (95% CI, 12-74%),
      respectively. One patient developed a lower respiratory tract infection after
      EBUS-TBNA, requiring inpatient admission. The cost of the EBUS-TBNA procedure per
      patient was L1,382 ($2,190). The mean cost of the EBUS-TBNA strategy was L1,892
      ($2,998) per patient, whereas a strategy of mediastinoscopy alone was
      significantly more costly at L3,228 ($5,115) per patient (P < 0.001). The EBUS
      TBNA strategy is less costly than mediastinoscopy if the cost per EBUS-TBNA
      procedure is less than L2,718 ($4,307) per patient. CONCLUSIONS: EBUS-TBNA is a
      safe, highly sensitive, and cost-saving initial investigation in patients with
      IML. Clinical trial registered with ClinicalTrials.gov (NCT00932854).

PMID- 22652034
TI  - Disease persistence in epidemiological models: the interplay between vaccination
      and migration.
AB  - We consider the interplay of vaccination and migration rates on disease
      persistence in epidemiological systems. We show that short-term and long-term
      migration can inhibit disease persistence. As a result, we show how migration
      changes how vaccination rates should be chosen to maintain herd immunity. In a
      system of coupled SIR models, we analyze how disease eradication depends
      explicitly on vaccine distribution and migration connectivity. The analysis
      suggests potentially novel vaccination policies that underscore the importance of
      optimal placement of finite resources.

PMID- 22652035
TI  - Direct lineage reprogramming to neural cells.
AB  - Recently we have witnessed an array of studies on direct reprogramming that
      describe induced inter conversion of mature cell types from higher organisms
      including human. While these studies reveal an unexpected level of plasticity of
      differentiated somatic cells, they also provide unprecedented opportunities to
      develop regenerative therapies for many debilitating disorders and model these
      'diseases-in-a-dish' for studying their pathophysiology. Here we review the
      current state of the art in direct lineage reprogramming to neural cells, and
      discuss the challenges that need to be addressed toward achieving the full
      potential of this exciting new technology.

PMID- 22652036
TI  - Modeling the transport and distribution of fecal coliform in a tidal estuary.
AB  - A laterally averaged two-dimensional fecal coliform transport model incorporated
      into hydrodynamic and salt modules was developed to simulate the fate and
      transport of fecal coliform in the tidal Danshui River estuary of northern
      Taiwan. We validated the developed model with measured data, including
      longitudinal velocity, salinity, and fecal coliform concentration, collected in
      2000. The simulated results of current, salinity, and fecal coliform
      concentration quantitatively agreed well with the measured data. The model
      sensitivity analysis indicated that the mortality rate plays an important role in
      the distribution of fecal coliform concentrations along the tidal Danshui River
      estuary to Tahan Stream. The validated model was applied to investigate the
      effects of different freshwater discharges at upstream boundaries on the
      distributions of fecal coliform. The results revealed that low freshwater
      discharge resulted in a higher fecal coliform concentration at upstream reaches
      but had little influence on the downstream of the estuary.

PMID- 22652037
TI  - Gadoxetic acid-enhanced 3.0 T MR imaging versus multidetector-row CT in the
      detection of colorectal metastases in fatty liver using intraoperative ultrasound
      and histopathology as a standard of reference.
AB  - OBJECTIVE: To compare the diagnostic value of gadoxetic acid-enhanced MRI at 3.0
      T with 64-row MDCT in the detection of colorectal liver metastases in diffuse
      fatty infiltration of the liver after neoadjuvant chemotherapy. METHODS: Twenty
      three patients with colorectal liver metastases and at moderate to severe
      steatosis (25-90%) underwent prospectively preoperative tri-phasic MDCT (Somatom
      Sensation 64, Siemens) and gadoxetic acid-enhanced MRI (3-T Magnetom Trio,
      Siemens). All patients underwent surgical resection of liver metastases.
      Intraoperative ultrasound (IOUS) was carried out, which served as the standard of
      reference, together with histopathology. RESULTS: Overall, 68 metastases (range,
      0.4-6 cm; 31/68 metastases [46%] <= 1 cm) were found at histology. MDCT detected
      49/68 lesions (72%), and MRI 66/68 (97%, p < 0.001). For lesions <= 1 cm, MDCT
      detected only 13/31 (41.9%) and MRI 29/31 (93%, p < 0.001). Eight false-positive
      lesions were detected by MDCT, seven small lesions by MRI. There was no
      statistically significant difference between the two modalities in the detection
      of lesions > 1 cm (p = 0.250). IOUS detected all metastases and revealed two
      false-positive diagnoses. CONCLUSION: Gadoxetic acid-enhanced 3.0 T MRI is
      superior to 64-row MDCT in detecting colorectal liver metastases <= 1 cm during
      preoperative staging in patients with liver steatosis. A combination of MRI and
      IOUS may further improve the outcome of surgical treatment.

PMID- 22652038
TI  - Adiponectin is inversely associated with ratio of serum levels of AGEs to sRAGE
      and vascular inflammation.

PMID- 22652039
TI  - Cardiac paraganglioma: clinical presentation, diagnostic approach and factors
      affecting short and long-term outcomes.
AB  - BACKGROUND: We describe our experience of the case of a young female who
      presented with chest pain and was found to have an intra-pericardial mass that
      was later confirmed to be a paraganglioma. Although preoperative magnetic
      resonance imaging (MRI) did not show any left atrial invasion, the patient died
      in the peri-operative period due to irreparable damage of the cardiac structures
      from extensive neoplastic invasion. We then performed a retrospective analysis of
      the available literature to find the factors associated with adverse surgical and
      long-term outcomes in patients with cardiac paraganglioma. METHODS: We found 93
      case reports of cardiac and/or pericardial paragangliomas in the literature.
      After exclusions, 82 cases were included in the final analysis. The patients were
      divided into two groups based on the outcome of surgical management. Univariate
      analysis was performed using SPSS software (Chicago, IL version 18), and the
      statistical significance was defined as a p-value<0.05. RESULTS AND CONCLUSIONS:
      The comparison of available demographic, clinical, pathological and laboratory
      parameters between the deceased and the surviving patients revealed that only the
      intra-cardiac location (p-value=0.021) and the development of metastases (p
      value<0.001) were independently associated with increased surgical and long-term
      mortality, respectively. The size of a paraganglioma, its functional status or
      invasion into the surrounding structures does not appear to affect short-or long
      term survival in these patients. The Kaplan-Meier survival curve showed excellent
      long-term prognosis for patients with a complete surgical removal of the
      neoplasm. Based on our experience, we also suggest preoperative imaging with a
      three dimensional cardiac CT and evaluation for cardiac transplantation before
      embarking on the surgical resection of these tumors.

PMID- 22652040
TI  - Mini-Mental State Examination performance in frail, pre-frail, and non-frail
      community dwelling older adults in Ermelino Matarazzo, Sao Paulo, Brazil.
AB  - BACKGROUND: Frailty in older adults is a multifactorial syndrome defined by low
      metabolic reserve, less resistance to stressors, and difficulty in maintaining
      organic homeostasis due to cumulative decline of multiple physiological systems.
      The relationship between frailty and cognition remains unclear and studies about
      Mini-Mental State Examination (MMSE) performance and frailty are scarce. The
      objective was to examine the association between frailty and cognitive
      functioning as assessed by the MMSE and its subdomains. METHODS: A cross
      sectional population-based study (FIBRA) was carried out in Ermelino Matarazzo, a
      poor subdistrict of the city of Sao Paulo, Brazil. Participants were 384
      community dwelling older adults, 65 years and older who completed the MMSE and a
      protocol to assess frailty criteria as described in the Cardiovascular Health
      Study (CHS). RESULTS: Frail older adults had significantly worse performance on
      the MMSE (p < 0.001 for total score). Linear regression analyses showed that the
      MMSE total score was influenced by age (p < 0.001), education (p < 0.001), family
      income (p < 0.001), and frailty status (p < 0.036). Being frail was associated
      more significantly with worse scores in Time Orientation (p < 0.004) and
      Immediate Memory (p < 0.001). CONCLUSIONS: Our data suggest that being frail is
      associated with worse cognitive performance, as assessed by the MMSE. It is
      recommended that the assessment of frail older adults should include the
      investigation of their cognitive status.

PMID- 22652041
TI  - Epidemiological and etiological characteristics of hand, foot, and mouth disease
      in Ningbo, China, 2008-2011.
AB  - BACKGROUND: Outbreaks of hand, foot, and mouth disease (HFMD) in central China
      have caused public health concerns since 2007. It is of particular public health
      significance to update epidemiology of HFMD in port cities. OBJECTIVE: To
      investigate epidemical, etiological and clinical characteristics of HFMD in
      Ningbo, China, from 2008 to 2011. STUDY DESIGN: From May 2008 to December 2011, a
      total of 37,404 HFMD cases including 196 severe and 12 fatal cases were
      investigated. Human enteroviruses from 2360 cases were determined by real-time RT
      PCR. The VP1 gene of EV71 from 78 cases and CA16 from 21 cases, the VP4 gene from
      28 cases, and full-length genomes of 10 isolates were analyzed. Neutralizing
      antibodies were evaluated in 258 healthy subjects. Parameters associated with
      severe HFMD were evaluated. RESULTS: Annual incidence of HFMD was 3066.8/100,000
      in the population of <=5 years. EV71 C4a, CA16 B1, and other enteroviruses
      accounted for 63.7%, 24.0% and 12.3%, respectively. The genomes of EV71 from
      fatal and non-fatal cases were nearly identical. The positive rates of
      neutralizing antibody to EV71 increased from 13.5% to 67.6% in 1- to 5-year
      healthy groups. The neutralizing antibody to CA16 B1 isolate was negative. EV71,
      exposure history and certain early manifestations including fever, vomiting, limb
      exanthema and peripheral neutrophil ratio were significantly associated with HFMD
      severity. CONCLUSIONS: HFMD mainly caused by EV71 C4a and CA16 B1 is seriously
      epidemic in Ningbo. Future emphasis should be paid on EV71 immuno-prophylaxis and
      early identification of severe cases upon the etiological and clinical
      characteristics.

PMID- 22652042
TI  - Modulating telomerase activity in tumor patients by targeting dyskerin binding
      site for hTR.
AB  - Telomeres shortening, which leads to apoptosis, is prevented by telomerase adding
      small repeated segments of DNA to the telomeres. The telomerase level has been
      correlated with progression of several cancer types, including acute leukemia,
      breast, prostate, lung cancer and melanoma. Suppression of telomerase activity
      was found to reduce metastatic potential but could have serious side effects in
      normal proliferative cells. One of the proteins stabilizing the telomerase
      complex called dyskerin reduces the maximum telomerase activity. We suggest a
      possible therapeutic agent which would disable the interaction of dyskerin and
      telomerase, but would not completely inhibit telomerase activity.

PMID- 22652043
TI  - Temperature dependence of accuracy of DNA polymerase I from Geobacillus
      anatolicus.
AB  - Klenow-like DNA polymerase I fragment from Geobacillus anatolicus (GF) was cloned
      and purified. The accuracy of GF was measured in vitro at three different
      temperatures under single turnover conditions as well as using a forward mutation
      assay. In pre-steady-state kinetic measurements, when temperature was raised from
      22  degrees C to 50  degrees C, the rate (k(pol)) for cognate dTTP and non
      cognate dATP nucleotide incorporations increased six- and four-fold,
      respectively, whereas the K(d) for both nucleotide incorporations changed only
      slightly. As a result, the error frequency was remained constant (~4 * 10(-4))
      over this temperature range. The accuracy of GF was also measured using a forward
      mutation assay during a single cycle of DNA synthesis of the lacZalpha
      complementation gene in M13mp2 DNA. In this assay, which scores various types of
      replication errors, mutant frequency of GF was 5 * 10(-3) at 72  degrees C which
      is four-fold higher than that of 37  degrees C.

PMID- 22652044
TI  - [Increased morbidity and use of Primary Care medical services in patients with
      major depressive disorder and their families: a retrospective cohort study].
AB  - OBJECTIVE: To study the impact of non-psychiatric medical visits by patients with
      Major Depressive Disorder (MDD) and their family members, compared to healthy
      people and their relatives in Primary Care. DESIGN: Retrospective cohort
      observational study. LOCATION: San Alberto Hurtado Primary Care Clinic, Santiago
      Chile. PARTICIPANTS: Patients diagnosed with MDD during 2008 were paired by
      gender, age, and educational level with 2 healthy controls. We followed-up 206
      patients with 310 family members and 412 controls with 588 relatives. MAIN
      MEASUREMENTS: During 1 year after the diagnosis, all health visits were assessed
      in patients and their family members and compared with healthy controls and their
      relatives. For statistical analysis we used U-Mann-Whitney, considering
      statistical significance with p values <=0.05. RESULTS: The relative risk of
      making a non-psychiatric medical visit in depressed patients was 1.43 (95% CI:
      1.19-1.67) and in their family members was 1.37 (95% CI: 1.16-1.58). The most
      frequent health complaints in patients were trauma, respiratory, and neurological
      problems. Family members visited physicians due trauma, psychiatric and
      endocrinological complaints. CONCLUSIONS: The patients with MDD and their family
      members have a higher rate of medical visits in Primary Care. A family-oriented
      treatment of these patients could improve clinical outcomes and reduce the
      patient overload in this setting.

PMID- 22652045
TI  - The breadth of the placental surface but not the length is associated with body
      size at birth.
AB  - Studies of pregnancies complicated by preeclampsia led to the suggestion that the
      surface of the placenta is aligned along two axes, measured by its breadth and
      length. It was hypothesised that tissue along the breadth serves as a nutrient
      sensor, responding to the mother's nutritional state and fetal nutritional
      demands, while tissue along the length has different functions. To develop this
      hypothesis we measured the breadth and length of the placental surface in 401
      neonates born in the King Khalid Hospital, Riyadh, Saudi Arabia, and related
      these measurements to the baby's body size. The breadth and length of the
      placental surface were highly correlated (coefficient = 0.7). Nevertheless, in a
      simultaneous regression with both measurements, only the breadth was associated
      with neonatal body size. There were strong trends of increasing birth weight,
      ponderal index, and the circumferences of the head, chest, abdomen and thigh with
      increasing placental breadth. In contrast no measurement of baby's body size was
      related to placental length. Birth weight increased by 125 g per cm increase in
      placental breadth (95% confidence interval 88 to 162, p < 0.001) but only by 20 g
      per cm increase in placental length (-13 to 53, p = 0.2). The corresponding
      figures for head circumference were 0.28 cm (0.17-0.39, p < 0.001) and 0.03 (
      0.07 to 0.14, p = 0.5). The associations between placental breadth and neonatal
      body size were strongest if the mother's height was below the median (157 cm).
      The associations between a larger breadth of the placental surface and a larger
      baby are consistent with the hypothesis that tissue along the breadth plays a key
      role in nutrient transfer from mother to baby. Mothers who are short in stature
      are known to have lower rates of protein turnover in pregnancy. In these
      circumstances the ability of the placenta to transfer amino acids to the fetus
      may be critical.

PMID- 22652046
TI  - Maternal-fetal resource allocation: co-operation and conflict.
AB  - Pregnancy is generally a co-operative interaction between mother and fetus in
      which the evolutionary genetic interests of both benefit from production of
      healthy offspring. While this view is largely supported by empirical data,
      Kinship Theory predicts that mother and fetus will disagree over the optimum
      level of maternal investment that maximises their respective fitnesses. This
      conflict will be more evident with polyandrous than monogamous mating systems,
      when resources are scarce and in late gestation when the fetus is growing
      maximally, particularly if conceptus mass is large relative to maternal mass. As
      the site of nutrient transfer, the placenta is pivotal in the tug-of-war between
      mother and fetus over resource allocation. It responds to both fetal signals of
      nutrient demand and maternal signals of nutrient availability and, by adapting
      its phenotype, regulates the distribution of available resources. These
      adaptations involve changes in placental size, morphology, transport
      characteristics, metabolism and hormone bioavailability. They are mediated by key
      growth regulatory, endocrine and nutrient supply genes responsive to mismatches
      between nutrient availability and the fetal genetic drive for growth. Indeed,
      evolution of genomic imprinting and placental secretion of hormones are believed
      to have been driven by maternal-fetal conflict over resource allocation. Although
      many of the specific mechanisms involved still have to be identified, the
      placenta confers optimal fitness on the offspring for its developmental
      environment by balancing conflict and cooperation in the allocation of resources
      through generation of nutrient transport phenotypes specific to the prevailing
      nutritional conditions and/or fetal genotype.

PMID- 22652047
TI  - Arterio-arterial vascular anastomoses in monochorionic placentas with and without
      twin-twin transfusion syndrome.
AB  - We performed a matched case-control study to analyze the placental
      angioarchitecture, in particular the diameter of arterio-arterial (AA)
      anastomoses in monochorionic placentas from pregnancies with twin-twin
      transfusion syndrome (TTTS) compared to a control group of uncomplicated
      monochorionic placentas. Placental angioarchitecture was analyzed using colored
      dye injection. AA anastomoses were detected in 37% (14/38) of TTTS placentas
      versus 91% (209/228) in control placentas (p < 0.001). The median diameter of AA
      anastomoses in the group with and without TTTS was 1.9 mm and 2 mm, respectively
      (p = 0.711). In conclusion, our findings show that AA anastomosis occur less
      frequently in TTTS placentas, supporting the concept of the protective role of AA
      anastomoses in TTTS. However, the size of the AA anastomosis, when present, does
      not appear to influence the pathophysiology of the disease.

PMID- 22652049
TI  - Behavioral barcoding in the cloud: embracing data-intensive digital phenotyping
      in neuropharmacology.
AB  - For decades, studying the behavioral effects of individual drugs and genetic
      mutations has been at the heart of efforts to understand and treat nervous system
      disorders. High-throughput technologies adapted from other disciplines (e.g.,
      high-throughput chemical screening, genomics) are changing the scale of data
      acquisition in behavioral neuroscience. Massive behavioral datasets are beginning
      to emerge, particularly from zebrafish labs, where behavioral assays can be
      performed rapidly and reproducibly in 96-well, high-throughput format. Mining
      these datasets and making comparisons across different assays are major
      challenges for the field. Here, we review behavioral barcoding, a process by
      which complex behavioral assays are reduced to a string of numeric features,
      facilitating analysis and comparison within and across datasets.

PMID- 22652048
TI  - Survival by self-destruction: a role for autophagy in the placenta?
AB  - Autophagy is a burgeoning area of research from yeast to humans. Although
      previously described as a death pathway, autophagy is now considered an important
      survival phenomenon in response to environmental stressors to which most organs
      are exposed. Despite an ever expanding literature in non-placental cells, studies
      of autophagy in the placenta are lagging. We review the regulation of autophagy,
      summarize available placental studies of autophagy, and highlight potential areas
      for future research. We believe that such studies will yield novel insights into
      how placentas protect the survival of the species by "self-eating".

PMID- 22652050
TI  - New CD1d agonists: synthesis and biological activity of 6"-triazole-substituted
      alpha-galactosyl ceramides.
AB  - Huisgen [3+2] dipolar cycloaddition of 6"-azido-6"-deoxy-alpha-galactosyl
      ceramide 11 with a range of alkynes (or a benzyne precursor) yielded a series of
      triazole-containing alpha-galactosyl ceramide (alpha-GalCer) analogues in high
      yield. These alpha-GalCer analogues and the precursor azide 11 were tested for
      their ability to activate iNKT cells and stimulate IL-2 cytokine secretion in
      vitro, and IFN-gamma and IL-4 cytokine secretion in vivo. Some of these
      analogues, specifically 11, 12b, 12f and 13, were more potent IL-2 stimulators
      than the prototypical CD1d agonist, alpha-GalCer 1. In terms of any cytokine
      bias, most of the triazole-containing analogues exhibited a small Th2 cytokine
      biasing response relative to that shown by alpha-GalCer 1. In contrast, the
      cycloaddition precursor, namely azide 11, provided a small Th1 cytokine-biasing
      response.

PMID- 22652051
TI  - Evaluation of novel antioxidant triterpenoid saponins from the halophyte
      Salicornia herbacea.
AB  - As a part of an ongoing search for novel antioxidants from the salt marsh plants,
      bioactivity-isolation and structure determination of constituents from Salicornia
      herbacea were performed. One new triterpenoid saponin (4), along with three known
      saponins (1-3), has been isolated from n-BuOH fraction of S. herbacea. On the
      basis of the spectroscopic methods, the structure of the new saponin 4 was
      elucidated as 3beta-hydroxy-23-oxo-30-noroleana-12, 20(29)-diene-28-oic acid 3-O
      beta-D-glucuronopyranosyl-28-O-beta-d-glucopyranoside. Scavenging effects of
      saponins 1-4 were examined on 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical and
      peroxynitrite. Particularly, saponin 3 exerted significant antioxidant activity
      on both authentic peroxynitrite and peroxynitrite generated from
      morpholinosydnonimine (SIN-1).

PMID- 22652052
TI  - Synthesis and biological evaluation of novel technetium-99m labeled
      phenylbenzoxazole derivatives as potential imaging probes for beta-amyloid
      plaques in brain.
AB  - Two uncharged (99m)Tc-labeled phenylbenzoxazole derivatives were biologically
      evaluated as potential imaging probes for beta-amyloid plaques. The (99m)Tc and
      corresponding rhenium complexes were synthesized by coupling monoamine-monoamide
      dithiol (MAMA) and bis(aminoethanethiol) (BAT) chelating ligand via a pentyloxy
      spacer to phenylbenzoxazole. The fluorescent rhenium complexes 6 and 9
      selectively stainined the beta-amyloid plaques on the sections of transgenic
      mouse, and showed high affinity for Abeta((1-42)) aggregates (K(i)=11.1 nM and
      14.3 nM, respectively). Autoradiography in vitro indicated that [(99m)Tc]6
      clearly labeled beta-amyloid plaques on the sections of transgenic mouse.
      Biodistribution experiments in normal mice revealed that [(99m)Tc]6 displayed
      moderate initial brain uptake (0.81% ID/g at 2 min), and quickly washed out from
      the brain (0.25% ID/g at 60 min). The preliminary results indicate that the
      properties of [(99m)Tc]6 are promising, although additional refinements are
      needed to improve the ability to cross the blood-brain barrier.

PMID- 22652053
TI  - Syntheses and biological activities of sulfoximine-based acyclic triaryl olefins.
AB  - Sulfoximine-based acyclic triaryl olefins 8 and 9 have been prepared and initial
      studies have been performed to determine their biological profiles. In contrast
      to their sulfonyl-substituted analog 2 sulfoximines 8 and 9 show low COX
      inhibitory activity. All compounds affect the estrogen receptors. While sulfone 2
      interacts exclusively with ER beta, sulfoximines 8 and 9 reveal almost equal
      blocking potencies for both estrogen receptors, ER alpha and ER beta. In the
      tested series, triaryl olefin 9a shows the highest inhibitory activities with 91%
      and 80%, respectively (at 10 MUM).

PMID- 22652054
TI  - Cryptic diversity among Western Palearctic tree frogs: postglacial range
      expansion, range limits, and secondary contacts of three European tree frog
      lineages (Hyla arborea group).
AB  - We characterize divergence times, intraspecific diversity and distributions for
      recently recognized lineages within the Hyla arborea species group, based on
      mitochondrial and nuclear sequences from 160 localities spanning its whole
      distribution. Lineages of H. arborea, H. orientalis, H. molleri have at least
      Pliocene age, supporting species level divergence. The genetically uniform
      Iberian H. molleri, although largely isolated by the Pyrenees, is parapatric to
      H. arborea, with evidence for successful hybridization in a small Aquitanian
      corridor (southwestern France), where the distribution also overlaps with H.
      meridionalis. The genetically uniform H. arborea, spread from Crete to Brittany,
      exhibits molecular signatures of a postglacial range expansion. It meets
      different mtDNA clades of H. orientalis in NE-Greece, along the Carpathians, and
      in Poland along the Vistula River (there including hybridization). The East
      European H. orientalis is strongly structured genetically. Five geographic
      mitochondrial clades are recognized, with a molecular signature of postglacial
      range expansions for the clade that reached the most northern latitudes.
      Hybridization with H. savignyi is suggested in southwestern Turkey. Thus, cryptic
      diversity in these Pliocene Hyla lineages covers three extremes: a genetically
      poor, quasi-Iberian endemic (H. molleri), a more uniform species distributed from
      the Balkans to Western Europe (H. arborea), and a well-structured Asia Minor
      Eastern European species (H. orientalis).

PMID- 22652055
TI  - A climate for speciation: rapid spatial diversification within the Sorex cinereus
      complex of shrews.
AB  - The cyclic climate regime of the late Quaternary caused dramatic environmental
      change at high latitudes. Although these events may have been brief in
      periodicity from an evolutionary standpoint, multiple episodes of allopatry and
      divergence have been implicated in rapid radiations of a number of organisms.
      Shrews of the Sorex cinereus complex have long challenged taxonomists due to
      similar morphology and parapatric geographic ranges. Here, multi-locus
      phylogenetic and demographic assessments using a coalescent framework were
      combined to investigate spatiotemporal evolution of 13 nominal species with a
      widespread distribution throughout North America and across Beringia into
      Siberia. For these species, we first test a hypothesis of recent differentiation
      in response to Pleistocene climate versus more ancient divergence that would
      coincide with pre-Pleistocene perturbations. We then investigate the processes
      driving diversification over multiple continents. Our genetic analyses highlight
      novel diversity within these morphologically conserved mammals and clarify
      relationships between geographic distribution and evolutionary history.
      Demography within and among species indicates both regional stability and rapid
      expansion. Ancestral ecological differentiation coincident with early
      cladogenesis within the complex enabled alternating and repeated episodes of
      allopatry and expansion where successive glacial and interglacial phases each
      promoted divergence. The Sorex cinereus complex constitutes a valuable model for
      future comparative assessments of evolution in response to cyclic environmental
      change.

PMID- 22652056
TI  - 11beta-Hydroxysteroid dehydrogenase type 1 inhibitors: novel agents for the
      treatment of metabolic syndrome and obesity-related disorders?
AB  - OBJECTIVE: Metabolic syndrome (MetS) and Cushing's syndrome share common
      features. It has been proposed that increased glucocorticoid activity at
      peripheral tissues may play a role in the pathogenesis of MetS and obesity
      related disorders. It is well-known that intracellular cortisol concentrations
      are determined not only by plasma levels but also by the activity of 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1) which catalyzes the conversion
      of inactive cortisone to active cortisol, especially in the liver and adipose
      tissue. Another isoenzyme exists, the 11beta-hydroxysteroid dehydrogenase type 2,
      which acts in the opposite direction inactivating cortisol to cortisone in the
      kidney. This review considers the significance of the 11beta-HSD1 inhibition in
      the treatment of several features of MetS and provides current data about the
      development of 11beta-HSD1 inhibitors, as new agents for this purpose.
      MATERIALS/METHODS: Using PubMed, we searched for publications during the last
      20years regarding the development of 11beta-HSD1 inhibitors. RESULTS: Emerging
      data from animal and human studies indicate an association of 11beta-HSD1 over
      expression with obesity and disorders in glucose and lipid metabolism. This has
      led to the hypothesis that selective inhibition of 11beta-HSD1 could be used to
      treat MetS and diabetes. Indeed, natural products and older agents such as
      thiazolidinediones and fibrates seem to exert an inhibitory effect on 11beta
      HSD1, ameliorating the cardiometabolic profile. In view of this concept, novel
      compounds, such as adamantyltriazoles, arylsulfonamidothiazoles,
      anilinothiazolones, BVT2733, INCB-13739, MK-0916 and MK-0736, are currently under
      investigation and the preliminary findings from both experimental and human
      studies show a favourable effect on glucose and lipid metabolism, weight
      reduction and adipokine levels. CONCLUSIONS: Many compounds inhibiting 11beta
      EtaSD1 are under development and preliminary data about their impact on glucose
      metabolism and obesity-related disorders are encouraging.

PMID- 22652058
TI  - Noradrenergic antidepressants increase cortical dopamine: potential use in
      augmentation strategies.
AB  - Most antidepressant treatments, based on serotonin (5-HT) and/or norepinephrine
      (NE) transporter blockade, show limited efficacy and slow onset of action,
      requiring the use of augmentation strategies. Here we report on a novel
      antidepressant strategy to selectively increase DA function in prefrontal cortex
      (PFC) without the potential tolerance problems associated to DA transporter
      blockade. This approach is based on previous observations indicating that
      extracellular DA in rat medial PFC (mPFC) - but not in nucleus accumbens (NAc) -
      arises from noradrenergic terminals and is sensitive to noradrenergic drugs. A
      low dose of reboxetine (3 mg/kg i.p.; NE reuptake inhibitor) non-significantly
      increased extracellular DA in mPFC. Interestingly, its combined administration
      with 5 mg/kg s.c. mirtazapine (non-selective alpha2-adrenoceptor antagonist)
      increased extracellular DA in mPFC (264 +/- 28%), but not in NAc. Extracellular
      NE (but not 5-HT) in mPFC was also enhanced by the combined treatment (472 +/-
      70%). Repeated (*3) reboxetine + mirtazapine administration produced a moderate
      additional increase in mPFC DA and markedly reduced the immobility time (-51%) in
      the forced-swim test. Neurochemical and behavioral effects of the reboxetine +
      mirtazapine combination persisted in rats pretreated with citalopram (3 mg/kg,
      s.c.), suggesting its potential usefulness to augment SSRI effects. In situ
      hybridization c-fos studies were performed to examine the brain areas involved in
      the above antidepressant-like effects, showing changes in c-fos expression in
      hippocampal and cortical areas. BDNF expression was also increased in the
      hippocampal formation. Overall, these results indicate a synergistic effect of
      the reboxetine + mirtazapine combination to increase DA and NE function in mPFC
      and to evoke robust antidepressant-like responses.

PMID- 22652057
TI  - Gating of NMDA receptor-mediated hippocampal spike timing-dependent potentiation
      by mGluR5.
AB  - Hippocampal long-term potentiation (LTP) is believed to be important for learning
      and memory. Experimentally, the pairing of precisely timed pre- and postsynaptic
      spikes within a time window of ~10 ms can induce timing-dependent LTP (tLTP), but
      the requirements for induction of tLTP change with development: in young rodents
      single postsynaptic spikes are sufficient to induce tLTP, whereas postsynaptic
      burst firing appears to be required in the adult. However, hippocampal neurons in
      vivo show theta-modulated single spike activities also in older hippocampus. Here
      we investigated the conditions for single spike pairing to induce tLTP at older
      CA3-CA1 synapses. We found that the pairing of single pre- and postsynaptic
      spikes could induce tLTP in older hippocampus when the postsynaptic neuronal
      membrane was depolarized and the pairing frequency exceeded ~4 Hz. The spike
      frequency requirement is postsynaptic, as tLTP could still be induced with
      presynaptic stimulation at 1 Hz as long as the postsynaptic spike frequency
      exceeded ~4 Hz, suggesting that postsynaptic theta-frequency activity is required
      for the successful induction of tLTP at older CA3-CA1 synapses. The induction of
      tLTP was blocked by an NMDA receptor antagonist and by the selective mGluR5
      blockers, MPEP and MTEP, whereas activation of mGluR1 and mGluR5 by DHPG relieved
      the postsynaptic spike frequency requirement for tLTP induction. These results
      suggest that activation of mGluR5 during single-spike pairing at older CA3-CA1
      synapses gates NMDA receptor-dependent tLTP.

PMID- 22652059
TI  - Orthosteric and allosteric drug binding sites in the Caenorhabditis elegans mgl-2
      metabotropic glutamate receptor.
AB  - The metabotropic glutamate receptors (mGluRs) are evolutionarily conserved from
      nematodes to vertebrates. The Caenorhabditis elegans (C. elegans) genome contains
      three mGluR genes referred to as mgl-1, mgl-2, and mgl-3. The aim of this study
      was to characterize the pharmacological profiles of orthosteric and allosteric
      mGluR ligands on mgl-2. A phylogenetic analysis revealed that mgl-2 is closely
      associated with the mammalian Group 1 mGluRs (mGluR1 and mGluR5) and is distinct
      from Group 2 and 3 mGluRs. The ligand binding domain of mgl-2 displayed higher
      homology to the rat Group 1 mGluRs binding domains compared to the level of
      homology in the heptahelical transmembrane domain regions. We found that, when
      transiently expressed in human embryonic kidney 293 cells, mgl-2 can be activated
      by glutamate and couples to human G-proteins to induce the release of
      intracellular calcium. Dose-response analyses revealed that mgl-2 has
      approximately a 15-20-fold lower affinity for glutamate and quisqualate compared
      to rat mGluR5. In contrast to orthosteric agonists, Group 1 negative allosteric
      modulators that target the transmembrane domain were ineffective at mgl-2.
      Surprisingly, CDPPB, an mGluR5 positive allosteric modulator, potentiated
      glutamate mediated activation of mgl-2, although MPEP and fenobam, two mGluR5
      antagonists that share similar binding residues with CDPPB were ineffective at
      mgl-2. These findings indicate that selective pressures on mGluR protein
      structures have resulted in conservation of the glutamate binding site, whereas
      the allosteric modulator sites have been subjected to greater divergent
      evolutionary changes.

PMID- 22652061
TI  - [Sneddon's syndrome].
AB  - Sneddon's syndrome is still raising some nosological and etiopathogenic
      questions. The occurrence of ischemic stroke in young adults especially in the
      presence of livedo racemosa should suggest the diagnosis and encourage to perform
      a skin biopsy, which could strengthen the diagnosis. Management begins with
      prevention of vascular risk factors and treatments based primarily on anti
      thrombotic. Large series of studies over several years could provide
      clarification of the etiopathogenesis of this syndrome and pave the way for the
      development of diagnostic criteria and new effective therapies in order to
      prevent progression to irreversible cognitive impairment.

PMID- 22652060
TI  - DEXH box RNA helicase-mediated mitochondrial reactive oxygen species production
      in Arabidopsis mediates crosstalk between abscisic acid and auxin signaling.
AB  - It is well known that abscisic acid (ABA) promotes reactive oxygen species (ROS)
      production through plasma membrane-associated NADPH oxidases during ABA
      signaling. However, whether ROS from organelles can act as second messengers in
      ABA signaling is largely unknown. Here, we identified an ABA overly sensitive
      mutant, abo6, in a genetic screen for ABA-mediated inhibition of primary root
      growth. ABO6 encodes a DEXH box RNA helicase that is involved in regulating the
      splicing of several genes of complex I in mitochondria. The abo6 mutant
      accumulated more ROS in mitochondria, as established using a mitochondrial
      superoxide indicator, circularly permuted yellow fluorescent protein. Two
      dominant-negative mutations in ABA insensitive1 (abi1-1) and abi2-1 greatly
      reduced ROS production in mitochondria. The ABA sensitivity of abo6 can also be
      compromised by the atrbohF mutation. ABA-mediated inhibition of seed germination
      and primary root growth in abo6 was released by the addition of reduced GSH and
      exogenous auxin to the medium. Expression of auxin-responsive markers ProDR5:GUS
      (for synthetic auxin response element D1-4 with site-directed mutants in the 5'
      end from soybean):beta-glucuronidase) and Indole-3-acetic acid inducible2:GUS was
      greatly reduced by the abo6 mutation. Hence, our results provide molecular
      evidence for the interplay between ABA and auxin through the production of ROS
      from mitochondria. This interplay regulates primary root growth and seed
      germination in Arabidopsis thaliana.

PMID- 22652062
TI  - Arthroscopic repair of large rotator cuff tears using the double-row technique:
      an analysis of surgeon experience on efficiency and outcomes.
AB  - BACKGROUND: Arthroscopic rotator cuff repair is one of the most commonly
      performed procedures in the orthopaedic specialty. The goal of this study was to
      evaluate the effect(s) of surgical experience on efficiency and patient outcomes
      after double-row rotator cuff repair. METHODS: A retrospective review of 69
      consecutive patients with large rotator cuff tears who underwent double-row
      arthroscopic rotator cuff repair by 1 surgeon from the start of practice was
      conducted. We divided the patients into 2 cohorts: group 1, early (first 18
      months of study period) (n = 35), and group 2, recent (final 12 months of study
      period) (n = 34). Outcome measures including American Shoulder and Elbow Surgeons
      score, Penn Shoulder Score, and range of motion were assessed preoperatively and
      at final follow-up. In addition, we compared the operative times between the
      groups. RESULTS: At a mean follow-up of 13.25 months, both cohorts showed
      significant improvement (P < .001) in American Shoulder and Elbow Surgeons scores
      (from 47.9 to 76.5 and from 43.6 to 79.4 in groups 1 and 2, respectively) and
      Penn Shoulder Scores (from 45.8 to 80 and from 38.7 to 79.6 in groups 1 and 2,
      respectively) postoperatively. The magnitude of change and final scores were
      similar between the groups. Similar improvements in range of motion were noted in
      both groups. Patients in group 1 had a statistically significantly longer mean
      operative time than those in group 2 (116 minutes vs 99.7 minutes, P = .036).
      CONCLUSION: Double-row rotator cuff repair provides predictable improvement in
      pain and function. It can be performed effectively early in a surgeon's career.
      However, with experience, efficiency is improved.

PMID- 22652064
TI  - Heterotopic ossification of the shoulder in patients with traumatic brain injury.
AB  - BACKGROUND: We retrospectively reviewed 10 consecutive patients (11 shoulders)
      with traumatic brain injury who underwent surgical resection of heterotopic
      ossification (HO) of the shoulder. Our primary research goal was to determine the
      change in range of motion (ROM) at the shoulder after resection of heterotopic
      ossification in patients with traumatic brain injury. Secondary research goals
      were to determine simple functional outcome gains related to activities of daily
      living and to determine complications in this patient cohort. METHODS AND
      MATERIALS: Data were collected retrospectively and included measured ROM of the
      shoulder and observed ability to perform daily activities. The average age of the
      patients was 33 years (range, 20 -45). RESULTS: Sagittal plane motion
      (flexion/extension) increased by 85.0 degrees , coronal plane motion
      (adduction/abduction) increased by 59.1 degrees , and axial plane motion
      (internal/external rotation) increased by 66.8 degrees  (P < .001). Nine patients
      increased independence with improved functional status (7 patients able to
      perform all 3 activities of feeding, grooming, and toiletry) (P < .001).
      CONCLUSION: Surgical resection of heterotopic ossification of the shoulder is an
      effective procedure to increase joint mobility and improve function.

PMID- 22652063
TI  - Prospective evaluation of postoperative compliance and outcomes after rotator
      cuff repair in patients with and without workers' compensation claims.
AB  - BACKGROUND: This study prospectively evaluated compliance and outcomes after
      rotator cuff repair in patients with and without Workers' Compensation claims.
      MATERIALS AND METHODS: From December 2007 to January 2010, 42 consecutive
      patients with Workers' Compensation claims (Work Comp group), and 50 consecutive
      patients without a Workers' Compensation claim (non-Work Comp group) underwent
      arthroscopic rotator cuff repair and were enrolled in this study. Compliance with
      a postoperative protocol of shoulder immobilization and physical therapy was
      documented. Patients were monitored clinically for a minimum of 12 months.
      RESULTS: Noncompliance with protocol was documented in 22 of 42 patients (52%) in
      the Work Comp group compared with 2 of 50 (4%) in the non-Work Comp group (P <
      .001). The Work Comp group had less improvement in preoperative to postoperative
      outcome scores for the American Shoulder and Elbow Surgeons (ASES) score (40.4 to
      60.1), Simple Shoulder Test (SST) score (3.9 to 6.0) and visual analog scale
      (VAS) for pain (7.0 to 3.5) compared with the non-Work Comp group (ASES, 41.7 to
      89.2; SST, 4.3 to 10.7; VAS, 6.2 to 0.35; P < .0001). The compliant Work Comp
      patients had more favorable results in final outcome scores (ASES, 73.1; SST,
      7.9; VAS, 1.5) than noncompliant Work Comp patients (ASES, 48.4; SST, 4.3; VAS,
      5.3; P < .0001). CONCLUSIONS: Patients with Workers' Compensation claims
      demonstrated a high rate of postoperative noncompliance (52%) compared with
      patients without Workers' Compensation claims (4%) after rotator cuff repair.
      Those Workers' Compensation patients who had no evidence of noncompliance had
      significant improvements and more favorable outcomes than the noncompliant
      Workers' Compensation patients.

PMID- 22652065
TI  - Functional outcomes of reverse shoulder arthroplasty compared with
      hemiarthroplasty for acute proximal humeral fractures.
AB  - BACKGROUND: Complex acute proximal humeral fractures may require prosthetic
      replacement of the proximal humerus. Reverse shoulder arthroplasty (RSA) has been
      suggested as an alternative to hemiarthroplasty in the management of such
      fractures. This study compared the functional outcomes of RSA with
      hemiarthroplasty in patients with acute proximal humeral fractures. MATERIALS AND
      METHODS: All patients who underwent RSA or shoulder hemiarthroplasty for acute
      proximal humeral fractures between January 1, 1999, and December 31, 2010 were
      identified from The New Zealand Joint Registry. Baseline information, operative
      characteristics, and postoperative outcomes (Oxford Shoulder Score [OSS] at 6
      months and 5 years, revision rate, and mortality rate) were examined and compared
      between the study groups. RESULTS: During the study period, 55 patients underwent
      RSA and 313 underwent shoulder hemiarthroplasty for acute proximal humeral
      fractures. Compared with hemiarthroplasty patients, RSA patients were
      significantly older (mean age, 79.6 vs 71.9 years; P < .001) and more often women
      (93% vs 78%, P = .013). The 6-month OSS was 28.1 for RSA and 27.9 for
      hemiarthroplasty, which was not significantly different (P = .923); however, the
      RSA group had a significantly better 5-year OSS than the hemiarthroplasty group
      (41.5 vs 32.3; P = .022). There was no significant difference between the RSA and
      hemiarthroplasty groups in revision rate per 100 component-years (1.7 vs 1.1; P =
      .747) or in 1-year mortality (3.5% vs 3.6%; P > .99). CONCLUSIONS: Patients with
      acute proximal humeral fractures who undergo RSA appear to achieve superior 5
      year functional outcomes compared with patients who undergo hemiarthroplasty.

PMID- 22652066
TI  - Sleep quality in caregivers of patients with Alzheimer's disease and Parkinson's
      disease and its relationship to quality of life.
AB  - BACKGROUND: Knowledge about sleep complaints of caregivers of patients with
      Alzheimer's disease (AD) and Parkinson's disease (PD) is limited, and we lack
      information about the relationship between caregivers' sleep problems and their
      quality of life (QoL). METHODS: We evaluated subjective sleep quality and its
      relationship to QoL in a group of 80 caregivers of patients with AD (ADCG, n =
      40) and PD (PDCG, n = 40), and in 150 controls. Information about night-time
      complaints was collected using the Pittsburgh Sleep Quality Index (PSQI). QoL was
      measured using the McGill QoL Questionnaire. RESULTS: Eighteen ADCG (45%), 22
      PDCG (55%), and 45 (30%) controls reported poor sleep quality. Mean global PSQI
      score of PDCG (6.25 +/- 3.9) was not significantly different from that of ADCG
      (5.8 +/- 3.5; p = 0.67). However, both PDCG and ADCG scored significantly higher
      than control group (4.3 +/- 3.1; p < 0.01). ADCG frequently reported difficulties
      falling asleep (72.5%) and disturbed sleep (100%). PDCG reported reduced
      subjective sleep quality (80%) and increased sleep disturbances (100%). Poor
      sleep quality was associated with depressive symptoms and correlated with QoL in
      caregivers of both groups, particularly the psychological symptoms domain.
      CONCLUSIONS: Among caregivers of patients with AD and PD, poor sleep quality is
      frequent and significantly linked to QoL and depressive symptoms. Identifying the
      nature of sleep disturbances not only in patients but also in their caregivers is
      important as appropriate treatment may lead to a better management of the needs
      of families coping with these patients.

PMID- 22652068
TI  - Automatic 80-250Hz "ripple" high frequency oscillation detection in invasive
      subdural grid and strip recordings in epilepsy by a radial basis function neural
      network.
AB  - OBJECTIVE: Recent studies give evidence that high frequency oscillations (HFOs)
      in the range between 80 Hz and 500 Hz in invasive recordings of epilepsy patients
      have the potential to serve as reliable markers of epileptogenicity. This study
      presents an algorithm for automatic HFO detection. METHODS: The presented HFO
      detector uses a radial basis function neural network. Input features of the
      detector were energy, line length and instantaneous frequency. Visual marked
      "ripple" HFOs (80-250 Hz) of 3 patients were used to train the neural network,
      and a further 8 patients served for the detector evaluation. RESULTS: Detector
      sensitivity and specificity were 49.1% and 36.3%. The linear and rank correlation
      between visual and automatic marked "ripple" HFO counts over the channels were
      significant for all recordings. A reference detector based on the line length
      achieved a sensitivity of 35.4% and a specificity of 46.8%. CONCLUSIONS:
      Automatic detections corresponded only partly to visual markings for single
      events but the relative distribution of brain regions displaying "ripple" HFO
      activity is reflected by the automated system. SIGNIFICANCE: The detector allows
      the automatic evaluation of brain areas with high HFO frequency, which is of high
      relevance for the demarcation of the epileptogenic zone.

PMID- 22652067
TI  - Neurogenic potential of progenitor cells isolated from postmortem human
      Parkinsonian brains.
AB  - The success of cellular therapies for Parkinson's disease (PD) will depend not
      only on a conducive growth environment in vivo, but also on the ex vivo
      amplification and targeted neural differentiation of stem/progenitor cells. Here,
      we demonstrate the in vitro proliferative and differentiation potential of
      stem/progenitor cells, adult human neural progenitor cells ("AHNPs") isolated
      from idiopathic PD postmortem tissue samples and, to a lesser extent, discarded
      deep brain stimulation electrodes. We demonstrate that these AHNPs can be
      isolated from numerous structures (e.g. substantia nigra, "SN") and are able to
      differentiate into both glia and neurons, but only under particular growth
      conditions including co-culturing with embryonic stem cell-derived neural
      precursors ("ESNPs"); this suggests that PD multipotent neural stem/progenitor
      cells do reside within the SN and other areas, but by themselves appear to lack
      key factors required for neuronal differentiation. AHNPs engraft following ex
      vivo expansion and transplantation into the rodent brain, demonstrating their
      regenerative potential. Our data demonstrate the presence and capacity of
      endogenous stem/progenitor cells in the PD brain.

PMID- 22652070
TI  - Gene expression profile of human peripheral blood mononuclear cells induced by
      Staphylococcus aureus lipoteichoic acid.
AB  - Lipoteichoic acid (LTA) is a major virulence factor of Gram-positive bacteria
      including Staphylococcus aureus. Despite its pivotal role in causing sepsis, the
      systemic immune responses to LTA in human cells are poorly understood. Here, we
      produced highly-pure and structurally-intact LTA from S. aureus and examined the
      gene expression profile of LTA-stimulated human peripheral blood mononuclear
      cells (PBMCs). The LTA preparation did not contain any detectable biologically
      active impurities and stimulated Toll-like receptor 2. Protein expression
      profiling using a cytokine array kit and ELISA revealed expression of MCP-1/CCL2,
      IL-6, and IL-1beta. We performed transcriptional profiling of PBMCs in response
      to S. aureus LTA using an Affymetrix genechip microarray. A total of 208 genes
      were significantly (fold change>1.5 and P<0.05) altered, with 157 up-regulated
      and 51 down-regulated genes in response to S. aureus LTA treatment. The up
      regulated genes were involved in recognition (30 genes), cellular adhesion (6
      genes), signal transduction (42 genes), co-stimulation (4 genes), chemokines,
      cytokines and their receptors (51 genes), apoptosis (9 genes), and negative
      regulation (15 genes). The down-regulated genes were involved in recognition (12
      genes), antigen processing and presentation (9 genes), signal transduction (27
      genes), and chemotaxis (3 genes). The microarray results were validated using
      real-time RT-PCR with 21 up-regulated genes and 9 down-regulated genes. Our
      results provide a more comprehensive overview of the transcriptional changes in
      PBMCs in response to S. aureus LTA, and contribute to the understanding of the
      pathophysiological role of S. aureus LTA during the systemic inflammatory
      response.

PMID- 22652069
TI  - Comparison of the meat quality and fatty acid composition of traditional fat
      tailed (Chall) and tailed (Zel) Iranian sheep breeds.
AB  - The aim of this study was to compare the meat quality of a traditional fat-tailed
      breed, Chall, to a tailed Iranian sheep breed, Zel. Lambs were grazed on pasture
      until weaning, and then were finished until slaughter at 10-12 months. Meat
      quality traits were measured on the longissimus dorsi (LD) muscle. Zel lambs
      accumulated more intramuscular fat (IMF) (p<0.01) and had lower shear force and
      drip loss than Chall lambs (p<0.05). The meat color of Zel lambs was higher for
      both a* (p<0.001) and b* (p<0.01) compared to Chall lambs. Meat from Zel lambs
      was more tender (p<0.01) and more juicy (p<0.05) than Chall lambs. The PUFA:SFA
      fatty acid ratio (P:S) was higher (p<0.05) and the n-6:n-3 PUFA ratio was lower
      in Chall compared to Zel lambs (p<0.05). Overall, these results show that the
      eating quality of Zel lambs was better, but that this was at the cost of less
      favorable fatty acid profiles and poorer meat color.

PMID- 22652071
TI  - Clinical value of decreased superoxide dismutase 1 in patients with epilepsy.
AB  - PURPOSE: Our previous study using proteomic analysis showed that superoxide
      dismutase 1 (SOD1) was significantly decreased in cerebrospinal fluid (CSF) of
      patients with epilepsy. However, the relevance of CSF-SOD1 alterations for the
      pathophysiology of epilepsy is currently unknown. The present study was intended
      to add to our understanding of this issue by measuring SOD1 levels in the CSF of
      patients with resistant epilepsy and non-resistant epilepsy. METHODS: A total of
      52 patients with epilepsy were recruited. 29 were non-resistant, 23 drug
      resistant. 20 individuals with no evidence of any neurological diseases were used
      as control. The concentration of CSF and serum SOD1 was measured by enzyme-linked
      immunosorbent assay. RESULTS: The concentration of CSF-SOD1 was decreased in both
      the drug-resistant (0.13 +/- 0.12 ng/ml) and the non-resistant epilepsy subgroups
      (0.29 +/- 0.23 ng/ml) compared to the control group (0.40 +/- 0.35 ng/ml). SOD1
      was significantly lower in the drug-resistant than the non-resistant epilepsy
      subgroup (P<0.05). CONCLUSION: SOD1 levels are decreased in the CSF of patients
      with epilepsy, especially of patients with intractable epilepsy. Low CSF-SOD1
      levels may be a predictor of antiepileptic drug resistance in patients with
      epilepsy.

PMID- 22652074
TI  - Advancing our understanding of aging using mathematical modeling of longitudinal
      data: Comment on "The quadratic hazard model for analyzing longitudinal data on
      aging, health, and the life span" by Anatoliy Yashin, Konstantin G Arbeev, Igor
      Akushevich, Alexander Kulminski, Svetlana V Ukraintseva, Eric Stallard, Kenneth C
      Land.

PMID- 22652072
TI  - Are we there yet?: Comment on "Nanopores: A journey towards DNA sequencing" by
      Meni Wanunu.

PMID- 22652075
TI  - Global Perspectives: assessing the impact of new technology.

PMID- 22652076
TI  - Multiple cytokine- and chemokine-producing primary testicular diffuse large B
      cell lymphoma, not otherwise specified.

PMID- 22652077
TI  - The first Italian patient with oculopharyngodistal myopathy: case report and
      considerations on differential diagnosis.
AB  - Oculopharyngodistal myopathy is a clinicopathologically distinct muscular
      disease. The underlying genetic defect has not been identified. We report here a
      43-year old woman with asymmetric bilateral ptosis, dysphonia, swallowing
      difficulties, and weakness of the distal leg muscles. Serum creatine kinase was
      moderately increased. Electromyography revealed myopathic changes and myotonic
      discharges. Both cardiologic and pneumologic evaluation did not reveal
      abnormalities. Muscle computed tomography images showed adipose tissue
      replacement of abdominis rectus, lateral vastus, adductor magnus, and both the
      posterior and anterior compartment muscles below the knee, with prevalent
      involvement of medial gastrocnemius muscle. Muscle biopsy uncovered changes in
      fiber size and the presence of atrophic fibers with rimmed vacuoles of varying
      diameter, and core-like structures in type I fibers. Diagnosis was performed
      according to clinical and histopathologic findings, which were fully consistent
      with the other reported patients, and on the genetic exclusion of similar
      conditions such as oculopharyngeal muscular dystrophy, myotonic dystrophy type 1
      and multi-minicore disease associated to RYR1 mutations. Differential diagnosis
      with mitochondrial myopathies, facioscapulohumeral muscular dystrophy and distal
      myopathies was also considered. This is the first Italian case of
      oculopharyngodistal myopathy, further suggesting the worldwide distribution of
      this rare neuromuscular disorder.

PMID- 22652078
TI  - Nerve, muscle and heart acute toxicity following oxaliplatin and capecitabine
      treatment.
AB  - Capecitabine plus oxaliplatin combination (XELOX) is the first-line treatment in
      metastatic colorectal cancer. Here we report a case of acute, severe but
      substantially reversible, neuromuscular and cardiac toxicity following XELOX
      chemotherapy. Muscle biopsy findings were consistent with a toxic myopathy with
      necrotizing features and vacuolar changes; COX-negative fibers were also present.
      The time course could support a main role for capecitabine, which may have some
      neurotoxic effects (more frequently central), but a detrimental interaction
      between the two drugs cannot be ruled out and further studies are needed.

PMID- 22652079
TI  - Compound heterozygosity in a South African patient with facioscapulohumeral
      muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is characterised by weakness and
      atrophy of the facial and shoulder girdle muscles. The FSHD phenotype segregates
      as an autosomal dominant trait and is caused by a deletion of an integral number
      of 3.3 kilobase pair (kb) repeat units on chromosome 4q35. Haplotype and Southern
      blot analyses of chromosome 4 resulted in the detection of two BlnI resistant
      deletion fragments, of 24 kb and 34 kb respectively, in a single individual from
      a South African FSHD family. The patient had moderate facial weakness and marked
      winging and high-riding of the scapulae with prominent pectoral and proximal arm
      muscle atrophy and weakness. Quadriceps and anterior tibial muscles were weak and
      the patient had bilateral foot drop. Although none of his children were
      symptomatic yet and only two showed very mild clinical signs, one had inherited
      the 24 kb deletion fragment, while the other two had the 34 kb deletion fragment.
      Molecular analysis conclusively identified the first compound heterozygous case
      in the South African FSHD population. However, in accordance with other studies
      of compound heterozygotes and clinical findings, no direct correlation between
      the clinical severity of this patient and the number of deletion fragments was
      observed.

PMID- 22652080
TI  - The multifaceted character of lymphotoxin beta in inflammatory myopathies and
      muscular dystrophies.
AB  - Lymphotoxin beta (LTbeta) regulates some inflammatory mechanisms that could be
      operative in idiopathic inflammatory myopathies (IM). We studied LTbeta and
      LTbetaR in inflammatory myopathies, normal and disease controls with
      immunohistochemistry, Western blotting and in situ hybridisation. LTbeta occurs
      in myonuclei of normal controls, implying its role in normal muscle physiology.
      LTbeta is strongly upregulated in regenerating muscle fibres in all myopathies,
      but not in denervated myofibres. Normal-appearing myofibres in inflammatory
      myopathies and muscular dystrophies express LTbeta possibly reflecting early
      myofibre damage, representing a hitherto undescribed pathologic hallmark.
      Furthermore, we visualised LTbeta in several inflammatory cell types in
      inflammatory myopathies, suggesting its involvement in the different inflammatory
      mechanisms underlying inflammatory myopathy subgroups.

PMID- 22652082
TI  - Simple procedure for fatty acid analysis of glycerophospholipids in Escherichia
      coli and Saccharomyces cerevisiae.
AB  - Rapid, convenient methods have been developed for fatty acid analysis of membrane
      glycerophospholipids in microorganisms. Fatty acid methyl esters derived from
      glycerophospholipids have been prepared directly from wet pellets of Escherichia
      coli cells or Saccharomyces cerevisiae spheroplasts without lipid extraction and
      fractionation in high yields under mild temperature conditions for analysis by
      gas chromatography.

PMID- 22652081
TI  - Novel solvent-free gelucire extract of Plumbago zeylanica using non-everted rat
      intestinal sac method for improved therapeutic efficacy of plumbagin.
AB  - INTRODUCTION: Various shortcomings of the available methods of extraction of
      plumbagin from Plumbago zeylanica using non-edible organic solvents coupled with
      the poor aqueous solubility and low bioavailability called for extracting
      plumbagin in a water soluble form via a single step technique using hydrophilic
      lipid Gelucire 44/14. METHODS: Gelucire extract of P. zeylanica (GPZ) was
      prepared and evaluated for extraction efficiency, High-performance thin layer
      chromatography (HPTLC) and thermal analysis. In vitro intestinal absorption and
      bioavailability of plumbagin from GPZ in comparison with that of aqueous (APZ),
      ethanolic extract (EPZ) and standard plumbagin studied using non-everted rat
      intestinal sac model. RESULTS: The GPZ showed significantly higher extraction
      efficiency (3.24+/-0.12% w/w) compared to ethanolic (EPZ) and aqueous (APZ)
      extraction, 2.48+/-0.16% w/w and 0.07+/-0.02% w/w respectively. GPZ displayed
      significantly higher Q(30min) (cumulative percentage absorption of plumbagin in
      30 min) and lower t(40%) (time required for 40% w/w drug absorption). The flux
      and apparent permeability coefficient in duodenum and ileum were 2, 3 and 6 fold
      higher than EPZ, standard plumbagin and APZ respectively. DISCUSSION: Improved
      therapeutic efficacy of plumbagin may be due to the micellar solubilization and
      consequent enhanced partitioning of plumbagin through intestinal by Gelucire
      which was reflected in the in vivo anti-inflammatory study conducted in rats.
      CONCLUSION: Thus extraction using Gelucire can be proclaimed as an efficient,
      economic and solvent-free technique for extraction of plumbagin and can be
      utilized for various clinically important water insoluble phytoconstituents in
      order to improve their biopharmaceutical properties.

PMID- 22652083
TI  - Biphasic addition strategy of hypoxanthine and thymidine for improving monoclonal
      antibody production.
AB  - In our previous study, we demonstrated that combinatorial addition of
      hypoxanthine (10 mg/L) and thymidine (2 mg/L) was able to stimulate initial cell
      growth and elevate volumetric concentration of antibody by 22% (Chen et al.,
      Appl. Microbiol. Biotechnol., 93, 169-178, 2012). In this study, a systematic
      study was carried out to investigate the effects of hypoxanthine and thymidine
      (H&T) on cell growth and antibody production in a much wider range of
      concentration. In addition, we pursued to establish a highly productive fed-batch
      culture via rationally designing H&T addition regime. It was found that both cell
      growth and antibody production in batch cultures were H&T concentration
      dependent. Specifically, a low concentration stimulated cell growth while
      exerting no influence on specific productivity (q(mAb)), and a high concentration
      inhibited cell growth, however, significantly enhancing q(mAb). Subsequent
      experiments with fed-batch shaking flasks demonstrated the feasibility of
      improving antibody production using a biphasic addition strategy for H&T:
      supplementing a low concentration of H&T during initial cell growth phase and a
      high concentration of H&T at the production phase. By applying the optimized
      feeding regime, a maximum viable cell density (VCD) of 6.45 * 10(6)cells/mL and
      volumetric antibody production of 632 mg/L were achieved in a 2 L-B.Braun
      bioreactor. Taken together, in this study, a biphasic H&T addition strategy for
      cell culture was developed, which hold great promise to improve antibody
      production.

PMID- 22652084
TI  - Gallic acid oxidizes Met residues in peptides released from bovine beta
      lactoglobulin by in vitro digestion.
AB  - Phenolic compounds (PCs) are frequently present in foods. However, little is
      known about the effect of PCs on enzymatic digestion process of food proteins and
      their products. In this study, the effect of gallic acid (GA) on in vitro
      digestion of beta-lactoglobulin (beta-LG) was investigated as a model system for
      analysis of the interaction between PCs and food proteins. GA showed no effect on
      the initial rate of beta-LG digestion. However, after 1.5 h of digestion, the
      observed degree of hydrolysis of beta-LG was lower in the presence than in the
      absence of GA. The peptides released from beta-LG were characterized by LC/IT-TOF
      MS and thirty peptides were identified. In particular, four new peaks were
      obtained following in vitro digestion of beta-LG in the presence of GA. Met(7),
      Met(24) and Met(145) in the peptides corresponding to these peaks were oxidized
      to methionine sulfoxide residues.

PMID- 22652085
TI  - Temperature dependence for anammox bacteria enriched from freshwater sediments.
AB  - The anoxic ammonium oxidation (anammox) process has been regarded as an
      attractive alternative process to treat wastewater containing high ammonium
      concentrations. By the implementation of anammox process at moderately low
      temperatures (<25 degrees C), the anammox process will be applied to more various
      industrial wastewater treatments. In this study, we established enrichment
      cultures of anammox bacteria from freshwater sediments by using an up-flow column
      reactor equipped with porous polyester nonwoven fabric at moderately low
      temperatures. Their nitrogen conversion rates reached 0.07-0.26 kg-N/m3/d.
      Phylogenetic analysis based on 16S rRNA gene from enrichment cultures revealed
      the presence of various anammox bacteria affiliated with unknown anammox bacteria
      as well as known anammox candidates, i.e., Candidatus Kuenenia stuttgartiensis
      and Candidatus Brocadia fulgida, Candidatus Scalindua wagneri. Anammox bacterial
      populations were influenced by enrichment conditions, i.e., seed sediments and
      temperature.

PMID- 22652086
TI  - Anti-allergic effect of lactic acid bacteria isolated from seed mash used for
      brewing sake is not dependent on the total IgE levels.
AB  - Lactic acid bacteria (LAB) in fermented foods have attracted considerable
      attention recently as treatment options for allergic diseases, the incidence of
      which has been increasing worldwide. Five strains of LAB isolated from kimoto,
      the traditional seed mash used for brewing sake, were screened for the ability to
      suppress IgE-mediated hypersensitivity reaction. Leuconostoc mesenteroides and
      Lactobacillus sakei, the normal microflora in kimoto, significantly suppressed
      the reaction, but the contaminant Lactobacillus curvatus did not. Next, we
      examined the effect of L. sakei LK-117 on atopic dermatitis in the NC/Nga mouse
      model. LK-117 supplementation significantly reduced the development of atopic
      dermatitis-like skin lesions in a manner independent of the IgE plasma levels. In
      the in vitro intestinal model constructed using the human intestinal epithelial
      cell line Caco-2 and murine macrophage cell line RAW 264.7, treatment with L.
      sakei LK-117, but not L. curvatus, significantly upregulated TNF-alpha production
      from RAW264.7 cells. This result indicated that L. sakei on the apical side
      affected the macrophages on the basolateral side, and this organism may have the
      ability to improve allergy symptoms mediated by the intestinal immune system.

PMID- 22652087
TI  - Acceleration of cellulose degradation and shift of product via methanogenic co
      culture of a cellulolytic bacterium with a hydrogenotrophic methanogen.
AB  - Although the effects of syntrophic relationships between bacteria and methanogens
      have been reported in some environments, those on cellulose decomposition using
      cellulolytic bacteria from methanogenic reactors have not yet been examined. The
      effects of syntrophic co-culture on the decomposition of a cellulosic material
      were investigated in a co-culture of Clostridium clariflavum strain CL-1 and the
      hydrogenotrophic methanogen Methanothermobacter thermautotrophicus strain DeltaH
      and a single-culture of strain CL-1 under thermophilic conditions. In this study,
      strain CL-1 was newly isolated as a cellulolytic bacterium from a thermophilic
      methanogenic reactor used for degrading garbage slurry. The degradation
      efficiency and cell density of strain CL-1 were 2.9- and 2.7-fold higher in the
      co-culture than in the single-culture after 60 h of incubation, respectively.
      Acetate, lactate and ethanol were the primary products in both cultures, and the
      concentration of propionate was low. The content of acetate to total organic
      acids plus ethanol was 59.3% in the co-culture. However, the ratio decreased to
      24.9% in the single-culture, although acetate was the primary product. Therefore,
      hydrogen scavenging by the hydrogenotrophic methanogen strain DeltaH could shift
      the metabolic pathway to the acetate production pathway in the co-culture.
      Increases in the cell density and the consequent acceleration of cellulose
      degradation in the co-culture would be caused by increases in adenosine 5'
      triphosphate (ATP) levels, as the acetate production pathway includes ATP
      generation. Syntrophic cellulose decomposition by the cellulolytic bacteria and
      hydrogenotrophic methanogens would be the dominant reaction in the thermophilic
      methanogenic reactor degrading cellulosic materials.

PMID- 22652088
TI  - Purification and characterization of an extracellular lipase from Mucor hiemalis
      f. corticola isolated from soil.
AB  - We have screened 39 microfungi isolates originated from soil in terms of
      lipolytic activity. Out of all screened, a novel strain of Mucor hiemalis f.
      corticola was determined to have the highest lipase activity. The extracellular
      lipase was produced in response to 2% glucose and 2.1% peptone. The lipase was
      purified 12.63-folds with a final yield of 27.7% through following purification
      steps; ammonium sulfate precipitation, dialysis, gel filtration column
      chromatography and ion exchange chromatography, respectively. MALDI-TOF MS
      analysis revealed 31% amino-acid identity to a known lipase from Rhizomucor
      miehei species. The molecular weight of the lipase was determined as 46 kDa using
      SDS-PAGE and analytical gel filtration. Optimal pH and temperature of the lipase
      were determined as 7.0 and 40 degrees C, respectively. The enzyme activity was
      observed to be stable at the pH range of 7.0-9.0. Thermostability assays
      demonstrated that the lipase was stable up to 50 degrees C for 60 min. The lipase
      was more stable in ethanol and methanol than other organic solvents tested.
      Furthermore, the activity of the lipase was slightly enhanced by SDS and PMSF. In
      the presence of p-NPP as substrate, K(m) and V(max) values of the lipase were
      calculated by Hanes-Woolf plot as 1.327 mM and 91.11 MUmol/min, respectively.

PMID- 22652089
TI  - Sociality of facial expressions in immersive virtual environments: a facial EMG
      study.
AB  - Immersive virtual environment technology is increasingly used by psychologists as
      a tool for researching social influence in realistic, yet experimentally
      controllable, settings. The present study demonstrates the validity and
      reliability of facial electromyography as a marker of affect in immersive virtual
      environments and further shows that the mere presence of virtual humans is enough
      to elicit sociality effects on facial expressiveness. Participants viewed
      pleasant and unpleasant images in a virtual room either alone or with two virtual
      humans present. The patterns of smiling and frowning activity elicited by
      positive and negative stimuli in the virtual environment were the same as those
      found in laboratory settings. Moreover, when viewing positive stimuli, smiling
      activity was greater when two agents were present than in the alone condition.
      The results provide new psychophysiological evidence for the potency of social
      agents in immersive virtual environments.

PMID- 22652090
TI  - Computer-assisted paramedic electrocardiogram interpretation with remote
      physician over-read: the future of prehospital STEMI care?

PMID- 22652091
TI  - The burden of atrial fibrillation on the hospital sector in Canada.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common disease that frequently requires
      acute hospital care; however, the cost of hospital care in Canada has not been
      reported. The purpose of this study was to estimate the cost of AF related to
      hospital-based care in Canada. METHODS: Analyses were conducted with 2 national
      administrative databases for the fiscal year 2007-2008. Databases included
      information for hospital admissions, day operations, and ambulatory care. Records
      with a most responsible diagnosis of AF, atrial flutter, or a diagnosis related
      to AF with a concomitant comorbidity of AF were included. Hospital costs were
      estimated, in 2010 Canadian dollars, by applying an average cost per weighted
      case to the resource intensity weight for each admission or visit and then adding
      the separate billable fee for admissions, surgical procedures, and interventions.
      RESULTS: In 2007-2008, the number of acute care admissions with AF as the most
      responsible diagnosis was 22,823, same-day surgical procedures was 5707, and
      emergency department visits was 58,066. The hospital costs attributable to AF
      were $815 million in 2010 Canadian dollars: $710 million for hospitalizations;
      $32 million for same-day surgical procedures; and $73 million for emergency
      department visits. Most of the acute care costs were for hospitalizations when AF
      was listed as a comorbidity ($558 million, or 69%). CONCLUSION: AF results in a
      substantial cost burden to the acute care hospital sector. Current hospital costs
      in AF patients are driven by the consequences of AF, while the costs for specific
      treatments for AF are relatively low.

PMID- 22652092
TI  - Sympathetic activation and vasoregulation in response to carbohydrate ingestion
      in patients with congestive heart failure.
AB  - BACKGROUND: In normal individuals, carbohydrate ingestion increases sympathetic
      vasoconstrictor activity but causes net vasodilatation in the same vascular bed.
      This study quantified the effects of carbohydrate ingestion on muscle sympathetic
      nerve activity (MSNA) and vasoregulation in patients with congestive heart
      failure (CHF). We hypothesized that high resting levels of MSNA in patients with
      CHF would blunt further increases in MSNA following carbohydrate ingestion and
      that their sympathetic activation would restrain vasodilatation. METHODS: Eleven
      patients with treated severe CHF and 11 age- and body mass index-matched normal
      controls (NCs) were studied for 2 hours after a high-carbohydrate meal. MSNA was
      measured by peroneal microneurography and calf blood flow by venous occlusion
      plethysmography. RESULTS: Patients with CHF had higher (P < 0.03) baseline MSNA
      (67 +/- 4.0 bursts/100 beats) than NCs (51 +/- 5.8 bursts/100 beats) and lower (P
      < 0.001) baroreflex sensitivity (2.1 +/- 0.58 ms/mm Hg) than NCs (7.4 +/- 1.2
      ms/mm Hg). Carbohydrate ingestion was associated with a significant increase in
      MSNA (P < 0.05) and calf blood flow (P < 0.01) with unchanged blood pressure in
      CHF patients. The magnitude of responses in CHF patients was not significantly
      different from that in NCs, but vasodilatation was delayed significantly (by 30
      minutes). CONCLUSIONS: Despite considerable resting sympathoexcitation and
      reduced baroreflex sensitivity, patients with CHF exhibited further increases in
      MSNA after carbohydrate ingestion, achieving levels similar to those after
      myocardial infarction. They also had temporally delayed vasodilatation, which
      could contribute to cachexia and muscle weakness in CHF patients. These
      observations suggest that high-carbohydrate meals may adversely affect CHF
      patients via altered autonomic tone and blood-flow patterns.

PMID- 22652093
TI  - Isolation and characterization of the immunostimulating beta-glucans of an edible
      mushroom Termitomyces robustus var.
AB  - Two immunostimulating beta-glucans, PS-I (water soluble) and PS-II (water
      insoluble) isolated from hot water extract of the fruiting bodies of an edible
      mushroom Termitomyces robustus var. showed significant macrophage, splenocyte,
      and thymocyte activation. On the basis of total hydrolysis, methylation analysis,
      periodate oxidation, and NMR experiments ((1)H, (13)C, DQF-COSY, TOCSY, DEPT-135,
      HSQC, and HMBC), the structure of the repeating unit of the polysaccharides is
      established as: PS-I: ->6)beta-D-Glcp-(1-> (Water-soluble glucan) PS-II: ->3)
      beta-D-Glcp-(1->3)-beta-D-Glcp-(1-> 6?1 beta-D-Glcp (Water-insoluble glucan,
      Termitan).

PMID- 22652094
TI  - A facile one-pot synthesis of biphenyl methyl-C-beta-D-glycosides.
AB  - Facile one-pot synthesis of biphenyl methyl-C-beta-D-glycosides was carried out
      using 4,6-O-protected-C-glycoside, aromatic aldehydes and malononitrile in
      pyrrolidine as an organocatalyst. Studies reveal that the use of pyrrolidine
      resulted in a better yield.

PMID- 22652095
TI  - Pre-treatment imaging and pathology characteristics of invasive breast cancers of
      limited extent: potential relevance for MRI-guided localized therapy.
AB  - BACKGROUND AND PURPOSE: Identifying breast cancers of limited extent (BCLE) is
      becoming increasingly important, especially for (image guided) minimally invasive
      therapy and partial breast irradiation. The purpose of this study is to establish
      characteristics at functional imaging and pathology associated with invasive
      BCLE. MATERIALS AND METHODS: Seventy-five patients (77 breasts) with invasive
      breast cancer were prospectively included. Excision specimens were processed
      using complete embedding. Microscopic findings were reconstructed and correlated
      with contrast-enhanced MRI. Tumors were stratified by absence or presence of
      occult disease >=10 mm from the MRI-visible lesion: BCLE and non-BCLE,
      respectively. Imaging and pathology characteristics were evaluated for their
      ability to discriminate between BCLE and non-BCLE. Multivariate binary logistic
      regression was employed to create a prediction model for BCLE. RESULTS: At
      univariate analysis, imaging as well as pathology characteristics were indicative
      for BCLE (39/77=51%). At multivariate analysis, a mass on mammography, the
      absence of tumor washout, positive ER and low quantity of DCIS in the index tumor
      retained significance (area under ROC curve=0.87). CONCLUSIONS: Pre-treatment
      assessment of mammography findings, MRI washout kinetics, ER status and quantity
      of DCIS in the index tumor has the potential to accurately identify BCLE.

PMID- 22652096
TI  - Incidence of isolated nodal failure in non-small cell lung cancer patients
      included in a prospective study of the value of PET-CT.
AB  - PURPOSE: Elective nodal irradiation (ENI) is not recommended in PET-CT-based
      radiotherapy for NSCLC despite a low level of evidence to support such
      guidelines. The aim of this investigation is to find out whether omitting ENI is
      safe. MATERIALS AND METHODS: Sixty-seven patients treated within a frame of a
      previously published prospective trial of the value of PET-CT were included in
      the analysis. Seventeen (25%) patients received ENI due to higher initial nodal
      involvement and in the remaining 50 patients (75%) with N0-N1 or single N2
      disease ENI was omitted. Isolated nodal failure (INF) was recorded if relapse
      occurred in the initially uninvolved regional lymph node without previous or
      simultaneous local recurrence regardless of the status of distant metastases.
      RESULTS: With a median follow-up of 32 months, the estimated 3-year overall
      survival was 42%, local progression-free interval was 55%, and distant metastases
      free interval was 62%. Three patients developed INF; all had ENI omitted from
      treatment, giving a final result of three INFs in 50 (6%) patients treated
      without ENI. In this group of patients, the 3-year cause-specific cumulative
      incidence of INF was 6.4% (95% confidence interval: 0-17%). CONCLUSIONS: The
      omission of ENI appears to be not as safe as suggested by current
      recommendations.

PMID- 22652097
TI  - Orexin-A induces anxiety-like behavior through interactions with glutamatergic
      receptors in the bed nucleus of the stria terminalis of rats.
AB  - The hypothalamic neuropeptide orexin (ORX) has been implicated in anxiety, and
      anxiety-like behaviors. The purpose of these studies was to determine the role of
      ORX, specifically orexin-A (ORX-A) in the bed nucleus of the stria terminalis
      (BNST) on anxiety-like behaviors in rats. Rats injected with ORX-A into the BNST
      displayed greater anxiety-like measures in the social interaction and elevated
      plus maze tests compared to vehicle treated controls. Such anxiety-like behaviors
      were not observed when the ORX-A injections were adjacent to the BNST, in the
      medial septum. The anxiety-inducing effects of direct infusions of ORX-A into the
      BNST may be a consequence of increased activation of BNST neurons. In BNST slice
      preparations using patch-clamp techniques, ORX-A induced membrane depolarization
      and generation of action potentials in a subset of BNST neurons. The anxiety
      inducing effects of ORX-A in the BNST also appear to be dependent on NMDA-type
      glutamate receptor activity, as pre-injecting the NMDA antagonist AP5 into the
      BNST blocked anxiogenic effects of local ORX-A injections. Injections of AMPA
      type receptor antagonists into the BNST prior to ORX-A resulted in only a partial
      attenuation of anxiety-like behaviors.

PMID- 22652098
TI  - The arterial and cardiac epicardium in development, disease and repair.
AB  - The importance of the epicardium covering the heart and the intrapericardial part
      of the great arteries has reached a new summit. It has evolved as a major
      cellular component with impact both in development, disease and more recently
      also repair potential. The role of the epicardium in development, its
      differentiation from a proepicardial organ at the venous pole (vPEO) and the
      differentiation capacities of the vPEO initiating cardiac epicardium (cEP) into
      epicardium derived cells (EPDCs) have been extensively described in recent
      reviews on growth and transcription factor pathways. In short, the epicardium is
      the source of the interstitial, the annulus fibrosus and the adventitial
      fibroblasts, and differentiates into the coronary arterial smooth muscle cells.
      Furthermore, EPDCs induce growth of the compact myocardium and differentiation of
      the Purkinje fibers. This review includes an arterial pole located PEO (aPEO)
      that provides the epicardium covering the intrapericardial great vessels. In
      avian and mouse models disturbance of epicardial outgrowth and maturation leads
      to a broad spectrum of cardiac anomalies with main focus on non-compaction of the
      myocardium, deficient annulus fibrosis, valve malformations and coronary artery
      abnormalities. The discovery that in disease both arterial and cardiac epicardium
      can again differentiate into EPDCs and thus reactivate its embryonic program and
      potential has highly broadened the scope of research interest. This reactivation
      is seen after myocardial infarction and also in aneurysm formation of the
      ascending aorta. Use of EPDCs for cell therapy show their positive function in
      paracrine mediated repair processes which can be additive when combined with the
      cardiac progenitor stem cells that probably share the same embryonic origin with
      EPDCs. Research into the many cell-autonomous and cell-cell-based capacities of
      the adult epicardium will open up new realistic therapeutic avenues.

PMID- 22652099
TI  - [Neisseria meningitidis serogroup Y infection with an atypical clinical
      presentation and diagnosis].

PMID- 22652100
TI  - [Associated factors and descriptive analysis of healthcare-related infective
      endocarditis in a tertiary reference hospital].
AB  - INTRODUCTION AND OBJECTIVES: The primary aim of this study was to evaluate
      associated factors, clinical features and prognosis of healthcare-related
      infective endocarditis cases compared with community-acquired and intravenous
      drug user-related episodes. Changes in the distribution of healthcare-related
      infective endocarditis were also analysed over time in our setting. METHODS: A
      prospective, observational, comparative study was performed. We included all the
      cases of infective endocarditis from January 2003 to June 2010, which were then
      classified into 2 groups: group 1: community-acquired and intravenous drug user
      origin, and group 2: nosocomial and non-nosocomial healthcare-related cases. The
      episodes were classified into 2 periods: period I: January/2003-June/2006 and
      period II: July/2006-June 2010. Univariate and multivariate analyses were
      performed. RESULTS: A total of 212 cases were included (group 1: 138, group 2:
      74). The variables of age (risk ratio 1.026; 95%CI, 1.003 to 1.049), Charlson
      index (risk radio 1.242; 95%CI, 1.067 to 1.445), and previous heart surgery (risk
      ratio 2.522; 95%CI, 1.353 to 4.701) were independently associated with healthcare
      related infective endocarditis on multivariate analysis. A non-significant
      increase was observed in healthcare-related cases of infective endocarditis in
      period II (40/104; 38.4% vs. 34/108; 31.4%). CONCLUSIONS: The recent increase in
      healthcare-related infective endocarditis seems to be associated with the use of
      invasive procedures in elderly patients with prosthetic cardiac valve, and those
      with a greater number of underlying diseases, especially patients with chronic
      renal failure on haemodialysis.

PMID- 22652102
TI  - Factors associated with external and internal lymphedema in patients with head
      and-neck cancer.
AB  - PURPOSE: The purpose of this study was to examine factors associated with the
      presence of secondary external and internal lymphedema in patients with head-and
      neck cancer (HNC). METHODS AND MATERIALS: The sample included 81 patients >=3
      months after HNC treatment. Physical and endoscopic examinations were conducted
      to determine if participants had external, internal, and/or combined head-and
      neck lymphedema. Logistic regression analysis was used to examine the factors
      associated with the presence of lymphedema. RESULTS: The following factors were
      statistically significantly associated with presence of lymphedema: (1) location
      of tumor associated with presence of external (P=.009) and combined lymphedema
      (P=.032); (2) time since end of HNC treatment associated with presence of
      external (P=.004) and combined lymphedema (P=.005); (3) total dosage of radiation
      therapy (P=.010) and days of radiation (P=.017) associated with the presence of
      combined lymphedema; (4) radiation status of surgical bed was associated with the
      presence of internal lymphedema, including surgery with postoperative radiation
      (P=.030) and (salvage) surgery in the irradiated field (P=.008); and (5) number
      of treatment modalities associated with external (P=.002), internal (P=.039), and
      combined lymphedema (P=.004). No demographic, health behavior-related, or
      comorbidity factors were associated with the presence of lymphedema in the
      sample. CONCLUSIONS: Select tumor and treatment parameters are associated with
      increased occurrence of lymphedema in patients with HNC. Larger and longitudinal
      studies are needed to identify adjusted effects and causative risk factors
      contributing to the development of lymphedema in patients with HNC.

PMID- 22652101
TI  - Silver clear nylon dressing is effective in preventing radiation-induced
      dermatitis in patients with lower gastrointestinal cancer: results from a phase
      III study.
AB  - PURPOSE: For patients with anal canal and advanced rectal cancer, chemoradiation
      therapy is a curative modality or an important adjunct to surgery. Nearly all
      patients treated with chemoradiation experience some degree of radiation-induced
      dermatitis (RID). Prevention and effective treatment of RID, therefore, is of
      considerable clinical relevance. The present phase III randomized trial compared
      the efficacy of silver clear nylon dressing (SCND) with that of standard skin
      care for these patients. METHODS AND MATERIALS: A total of 42 rectal or anal
      canal cancer patients were randomized to either a SCND or standard skin care
      group. SCND was applied from Day 1 of radiation therapy (RT) until 2 weeks after
      treatment completion. In the control arm, sulfadiazine cream was applied at the
      time of skin dermatitis. Printed digital photographs taken 2 weeks prior to, on
      the last day, and two weeks after the treatment completion were scored by 10
      blinded readers, who used the common toxicity scoring system for skin dermatitis.
      RESULTS: The radiation dose ranged from 50.4 to 59.4 Gy, and there were no
      differences between the 2 groups. On the last day of RT, when the most severe RID
      occurs, the mean dermatitis score was 2.53 (standard deviation [SD], 1.17) for
      the standard and 1.67 (SD, 1.2; P=.01) for the SCND arm. At 2 weeks after RT, the
      difference was 0.39 points in favor of SCND (P=.39). There was considerable
      intraclass correlation among the 10 observers. CONCLUSIONS: Silver clear nylon
      dressing is effective in reducing RID in patients with lower gastrointestinal
      cancer treated with combined chemotherapy and radiation treatment.

PMID- 22652103
TI  - Patient positioning based on a radioactive tracer implanted in patients with
      localized prostate cancer: a performance and safety evaluation.
AB  - PURPOSE: To evaluate the performance and safety of a radiation therapy
      positioning system (RealEye) based on tracking a radioactive marker (Tracer)
      implanted in patients with localized prostate cancer. METHODS AND MATERIALS: We
      performed a single-arm multi-institutional trial in 20 patients. The iridium-192
      ((192)Ir)-containing Tracer was implanted in the patient together with 4 standard
      gold seed fiducials. Patient prostate-related symptoms were evaluated with the
      International Prostate Symptom Score (IPSS) questionnaire. Computed tomography
      (CT) was performed for treatment planning, during treatment, and after treatment
      to evaluate the migration stability of the Tracer. At 5 treatment sessions, cone
      beam CT was performed to test the positioning accuracy of the RealEye. RESULTS:
      The Tracer was successfully implanted in all patients. No device or procedure
      related adverse events occurred. Changes in IPSS scores were limited. The
      difference between the mean change in Tracer-fiducial distance and the mean
      change in fiducial-fiducial distance was -0.39 mm (95% confidence interval [CI]
      upper boundary, -0.22 mm). The adjusted mean difference between Tracer position
      according to RealEye and the Tracer position on the CBCT for all patients was
      1.34 mm (95% CI upper boundary, 1.41 mm). CONCLUSIONS: Implantation of the Tracer
      is feasible and safe. Migration stability of the Tracer is good. Prostate
      patients can be positioned and monitored accurately by using RealEye.

PMID- 22652104
TI  - External beam accelerated partial-breast irradiation using 32 gy in 8 twice-daily
      fractions: 5-year results of a prospective study.
AB  - PURPOSE: External beam accelerated partial breast irradiation (APBI) is an
      increasingly popular technique for treatment of patients with early stage breast
      cancer following breast-conserving surgery. Here we present 5-year results of a
      prospective trial. METHODS AND MATERIALS: From October 2003 through November
      2005, 98 evaluable patients with stage I breast cancer were enrolled in the first
      dose step (32 Gy delivered in 8 twice-daily fractions) of a prospective, multi
      institutional, dose escalation clinical trial of 3-dimensional conformal external
      beam APBI (3D-APBI). Median age was 61 years; median tumor size was 0.8 cm; 89%
      of tumors were estrogen receptor positive; 10% had a triple-negative phenotype;
      and 1% had a HER-2-positive subtype. Median follow-up was 71 months (range, 2-88
      months; interquartile range, 64-75 months). RESULTS: Five patients developed
      ipsilateral breast tumor recurrence (IBTR), for a 5-year actuarial IBTR rate of
      5% (95% confidence interval [CI], 1%-10%). Three of these cases occurred in
      patients with triple-negative disease and 2 in non-triple-negative patients, for
      5-year actuarial IBTR rates of 33% (95% CI, 0%-57%) and 2% (95% CI, 0%-6%;
      P<.0001), respectively. On multivariable analysis, triple-negative phenotype was
      the only predictor of IBTR, with borderline statistical significance after
      adjusting for tumor grade (P=.0537). CONCLUSIONS: Overall outcomes were
      excellent, particularly for patients with estrogen receptor-positive disease.
      Patients in this study with triple-negative breast cancer had a significantly
      higher IBTR rate than patients with other receptor phenotypes when treated with
      3D-APBI. Larger, prospective 3D-APBI clinical trials should continue to evaluate
      the effect of hormone receptor phenotype on IBTR rates.

PMID- 22652105
TI  - Stereotactic radiosurgery of the postoperative resection cavity for brain
      metastases: prospective evaluation of target margin on tumor control.
AB  - PURPOSE: Given the neurocognitive toxicity associated with whole-brain
      irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of
      brain metastases are desirable. Our initial experience with stereotactic
      radiosurgery (SRS) targeting the resection cavity showed promising results. We
      examined the outcomes of postoperative resection cavity SRS to determine the
      effect of adding a 2-mm margin around the resection cavity on local failure (LF)
      and toxicity. PATIENTS AND METHODS: We retrospectively evaluated 120 cavities in
      112 patients treated from 1998-2009. Factors associated with LF and distant brain
      failure (DF) were analyzed using competing risks analysis, with death as a
      competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier
      product-limit method; variables associated with OS were evaluated using the Cox
      proportional hazards and log rank tests. RESULTS: The 12-month cumulative
      incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%,
      respectively. On univariate analysis, expansion of the cavity with a 2-mm margin
      was associated with decreased LF; the 12-month cumulative incidence rates of LF
      with and without margin were 3% and 16%, respectively (P=.042). The 12-month
      toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On
      multivariate analysis, melanoma histology (P=.038) and number of brain metastases
      (P=.0097) were associated with higher DF. The median OS time was 17 months
      (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided
      in 72% of the patients. CONCLUSION: Adjuvant SRS targeting the resection cavity
      of brain metastases results in excellent local control and allows WBRT to be
      avoided in a majority of patients. A 2-mm margin around the resection cavity
      improved local control without increasing toxicity compared with our prior
      technique with no margin.

PMID- 22652106
TI  - Meta-analysis of the alpha/beta ratio for prostate cancer in the presence of an
      overall time factor: bad news, good news, or no news?
AB  - PURPOSE: To present a novel method for meta-analysis of the fractionation
      sensitivity of tumors as applied to prostate cancer in the presence of an overall
      time factor. METHODS AND MATERIALS: A systematic search for radiation dose
      fractionation trials in prostate cancer was performed using PubMed and by manual
      search. Published trials comparing standard fractionated external beam radiation
      therapy with alternative fractionation were eligible. For each trial the
      alpha/beta ratio and its 95% confidence interval (CI) were extracted, and the
      data were synthesized with each study weighted by the inverse variance. An
      overall time factor was included in the analysis, and its influence on alpha/beta
      was investigated. RESULTS: Five studies involving 1965 patients were included in
      the meta-analysis of alpha/beta. The synthesized alpha/beta assuming no effect of
      overall treatment time was -0.07 Gy (95% CI -0.73-0.59), which was increased to
      0.47 Gy (95% CI -0.55-1.50) if a single highly weighted study was excluded. In a
      separate analysis, 2 studies based on 10,808 patients in total allowed extraction
      of a synthesized estimate of a time factor of 0.31 Gy/d (95% CI 0.20-0.42). The
      time factor increased the alpha/beta estimate to 0.58 Gy (95% CI -0.53-1.69)/1.93
      Gy (95% CI -0.27-4.14) with/without the heavily weighted study. An analysis of
      the uncertainty of the alpha/beta estimate showed a loss of information when the
      hypofractionated arm was underdosed compared with the normo-fractionated arm.
      CONCLUSIONS: The current external beam fractionation studies are consistent with
      a very low alpha/beta ratio for prostate cancer, although the CIs include
      alpha/beta ratios up to 4.14 Gy in the presence of a time factor. Details of the
      dose fractionation in the 2 trial arms have critical influence on the information
      that can be extracted from a study. Studies with unfortunate designs will supply
      little or no information about alpha/beta regardless of the number of subjects
      enrolled.

PMID- 22652108
TI  - Assessment of uncertainties in treatment planning for scanned ion beam therapy of
      moving tumors.
AB  - PURPOSE: To provide methods for quantification of uncertainties in 4-dimensional
      (4D) treatment during treatment planning. METHODS AND MATERIALS: Uncertainty
      information was generated by multiple 4D treatment simulations with varying
      parameters. Sampled data were analyzed using uncertainty visualization methods
      that have been added to common treatment plan evaluation methods (eg, dose-volume
      histogram and dose distribution analysis). To illustrate the potential of the
      introduced methods, uncertainty analysis was completed for a single lung cancer
      case using 3 motion mitigation techniques: gating, slice-by-slice rescanning, and
      breath-controlled rescanning. RESULTS: By repeating 4D dose calculations with
      varying parameters, we were able to show local uncertainties in dose
      distributions and to evaluate the stability of treatment setups. The new methods
      were found suitable for uncertainty evaluation in 4D treatment planning of moving
      tumors. Calculation time of the uncertainty base data was time consuming but
      contrivable overnight. CONCLUSIONS: Uncertainty analysis and visualization for 4D
      treatment planning provide an important tool in the decision process for an
      optimal treatment approach.

PMID- 22652107
TI  - Accuracy evaluation of a 3-dimensional surface imaging system for guidance in
      deep-inspiration breath-hold radiation therapy.
AB  - PURPOSE: To investigate the applicability of 3-dimensional (3D) surface imaging
      for image guidance in deep-inspiration breath-hold radiation therapy (DIBH-RT)
      for patients with left-sided breast cancer. For this purpose, setup data based on
      captured 3D surfaces was compared with setup data based on cone beam computed
      tomography (CBCT). METHODS AND MATERIALS: Twenty patients treated with DIBH-RT
      after breast-conserving surgery (BCS) were included. Before the start of
      treatment, each patient underwent a breath-hold CT scan for planning purposes.
      During treatment, dose delivery was preceded by setup verification using CBCT of
      the left breast. 3D surfaces were captured by a surface imaging system
      concurrently with the CBCT scan. Retrospectively, surface registrations were
      performed for CBCT to CT and for a captured 3D surface to CT. The resulting setup
      errors were compared with linear regression analysis. For the differences between
      setup errors, group mean, systematic error, random error, and 95% limits of
      agreement were calculated. Furthermore, receiver operating characteristic (ROC)
      analysis was performed. RESULTS: Good correlation between setup errors was found:
      R(2)=0.70, 0.90, 0.82 in left-right, craniocaudal, and anterior-posterior
      directions, respectively. Systematic errors were <=0.17 cm in all directions.
      Random errors were <=0.15 cm. The limits of agreement were -0.34-0.48, -0.42
      0.39, and -0.52-0.23 cm in left-right, craniocaudal, and anterior-posterior
      directions, respectively. ROC analysis showed that a threshold between 0.4 and
      0.8 cm corresponds to promising true positive rates (0.78-0.95) and false
      positive rates (0.12-0.28). CONCLUSIONS: The results support the application of
      3D surface imaging for image guidance in DIBH-RT after BCS.

PMID- 22652109
TI  - Aspirin and statin nonuse associated with early biochemical failure after
      prostate radiation therapy.
AB  - PURPOSE: To present the largest retrospective series investigating the effect of
      aspirin and statins, which are hypothesized to have antineoplastic properties, on
      biochemical failure (nadir plus 2 ng/mL) after prostate radiation therapy (RT).
      METHODS AND MATERIALS: Between 1989 and 2006, 2051 men with clinically localized
      prostate cancer received definitive RT alone (median dose, 76 Gy). The rates of
      aspirin use and statin use (defined as any use at the time of RT or during follow
      up) were 36% and 34%, respectively. The primary endpoint of the study was an
      interval to biochemical failure (IBF) of less than 18 months, which has been
      shown to be the single strongest predictor of distant metastasis, prostate cancer
      survival, and overall survival after RT. Patient demographic characteristics and
      tumor staging factors were assessed with regard to associations with the
      endpoint. Univariate analysis was performed with the chi(2) test for categorical
      variables and the Wilcoxon test for continuous variables. Multivariable analysis
      was performed with a multiple logistic regression. RESULTS: The median follow-up
      was 75 months. Univariate analysis showed that an IBF of less than 18 months was
      associated with aspirin nonuse (P<.0001), statin nonuse (P<.0001), anticoagulant
      nonuse (P=.0006), cardiovascular disease (P=.0008), and prostate-specific antigen
      (continuous) (P=.008) but not with Gleason score, age, RT dose, or T stage. On
      multivariate analysis, only aspirin nonuse (P=.0012; odds ratio, 2.052 [95%
      confidence interval, 1.328-3.172]) and statin nonuse (P=.0002; odds ratio, 2.465
      [95% confidence interval, 1.529-3.974]) were associated with an IBF of less than
      18 months. CONCLUSIONS: In patients who received RT for prostate cancer, aspirin
      or statin nonuse was associated with early biochemical failure, a harbinger of
      distant metastasis and death. Further study is needed to confirm these findings
      and to determine the optimal dosing and schedule, as well as the relative
      benefits and risks, of both therapies in combination with RT.

PMID- 22652110
TI  - Delayed complications in patients surviving at least 3 years after stereotactic
      radiosurgery for brain metastases.
AB  - PURPOSE: Little is known about delayed complications after stereotactic
      radiosurgery in long-surviving patients with brain metastases. We studied the
      actual incidence and predictors of delayed complications. PATIENTS AND METHODS:
      This was an institutional review board-approved, retrospective cohort study that
      used our database. Among our consecutive series of 2000 patients with brain
      metastases who underwent Gamma Knife radiosurgery (GKRS) from 1991-2008, 167
      patients (8.4%, 89 women, 78 men, mean age 62 years [range, 19-88 years]) who
      survived at least 3 years after GKRS were studied. RESULTS: Among the 167
      patients, 17 (10.2%, 18 lesions) experienced delayed complications (mass lesions
      with or without cyst in 8, cyst alone in 8, edema in 2) occurring 24.0-121.0
      months (median, 57.5 months) after GKRS. The actuarial incidences of delayed
      complications estimated by competing risk analysis were 4.2% and 21.2% at the
      60th month and 120th month, respectively, after GKRS. Among various pre-GKRS
      clinical factors, univariate analysis demonstrated tumor volume-related factors:
      largest tumor volume (hazard ratio [HR], 1.091; 95% confidence interval [CI],
      1.018-1.154; P=.0174) and tumor volume<=10 cc vs >10 cc (HR, 4.343; 95% CI, 1.444
      12.14; P=.0108) to be the only significant predictors of delayed complications.
      Univariate analysis revealed no correlations between delayed complications and
      radiosurgical parameters (ie, radiosurgical doses, conformity and gradient
      indexes, and brain volumes receiving >5 Gy and >12 Gy). After GKRS, an area of
      prolonged enhancement at the irradiated lesion was shown to be a possible risk
      factor for the development of delayed complications (HR, 8.751; 95% CI, 1.785
      157.9; P=.0037). Neurosurgical interventions were performed in 13 patients (14
      lesions) and mass removal for 6 lesions and Ommaya reservoir placement for the
      other 8. The results were favorable. CONCLUSIONS: Long-term follow-up is crucial
      for patients with brain metastases treated with GKRS because the risk of
      complications long after treatment is not insignificant. However, even when
      delayed complications occur, favorable outcomes can be expected with timely
      neurosurgical intervention.

PMID- 22652111
TI  - High-dose-rate prostate brachytherapy consistently results in high quality
      dosimetry.
AB  - PURPOSE: We performed a dosimetry analysis to determine how well the goals for
      clinical target volume coverage, dose homogeneity, and normal tissue dose
      constraints were achieved with high-dose-rate (HDR) prostate brachytherapy.
      METHODS AND MATERIALS: Cumulative dose-volume histograms for 208 consecutively
      treated HDR prostate brachytherapy implants were analyzed. Planning was based on
      ultrasound-guided catheter insertion and postoperative CT imaging; the contoured
      clinical target volume (CTV) was the prostate, a small margin, and the proximal
      seminal vesicles. Dosimetric parameters analyzed for the CTV were D90, V90, V100,
      V150, and V200. Dose to the urethra, bladder, bladder balloon, and rectum were
      evaluated by the dose to 0.1 cm(3), 1 cm(3), and 2 cm(3) of each organ, expressed
      as a percentage of the prescribed dose. Analysis was stratified according to
      prostate size. RESULTS: The mean prostate ultrasound volume was 38.7 +/- 13.4
      cm(3) (range: 11.7-108.6 cm(3)). The mean CTV was 75.1 +/- 20.6 cm(3) (range:
      33.4-156.5 cm(3)). The mean D90 was 109.2% +/- 2.6% (range: 102.3%-118.4%).
      Ninety-three percent of observed D90 values were between 105 and 115%. The mean
      V90, V100, V150, and V200 were 99.9% +/- 0.05%, 99.5% +/- 0.8%, 25.4% +/- 4.2%,
      and 7.8% +/- 1.4%. The mean dose to 0.1 cm(3), 1 cm(3), and 2 cm(3) for organs at
      risk were: Urethra: 107.3% +/- 3.0%, 101.1% +/- 14.6%, and 47.9% +/- 34.8%;
      bladder wall: 79.5% +/- 5.1%, 69.8% +/- 4.9%, and 64.3% +/- 5.0%; bladder
      balloon: 70.3% +/- 6.8%, 59.1% +/- 6.6%, and 52.3% +/- 6.2%; rectum: 76.3% +/-
      2.5%, 70.2% +/- 3.3%, and 66.3% +/- 3.8%. There was no significant difference
      between D90 and V100 when stratified by prostate size. CONCLUSIONS: HDR
      brachytherapy allows the physician to consistently achieve complete prostate
      target coverage and maintain normal tissue dose constraints for organs at risk
      over a wide range of target volumes.

PMID- 22652112
TI  - Impact of neoadjuvant prostate-specific antigen kinetics on biochemical failure
      and prostate cancer mortality: results from a prospective patient database.
AB  - PURPOSE: To confirm findings from an earlier report showing that neoadjuvant (NA)
      prostate-specific antigen (PSA) halving time (PSAHT) impacts biochemical failure
      (BF) rates, and to examine its association with prostate cancer-specific survival
      (PCSS), in a large prospective cohort of patients. METHODS AND MATERIALS: A total
      of 502 patients were selected from a prospective database, who had localized
      prostate adenocarcinoma treated with 2-12 months of neoadjuvant androgen
      deprivation therapy (N-ADT) followed by external beam radiation therapy (EBRT)
      between 1994 and 2000, and had at least 2 NA PSA values. Seventy-four percent of
      patients had high-risk prostate cancer. Median initial PSA value, N-ADT duration,
      total ADT duration, and radiation therapy dose were 14 ng/mL, 6.9 months, 10.8
      months, and 68 Gy, respectively. RESULTS: At a median follow-up of 9.9 years, 210
      patients have had a BF. Median PSAHT was 18 days. On univariate analysis, PSAHT
      was not shown to predict for BF (P=.69) or PCSS (P=.28). However, NA nadir PSA
      (nanPSA) and post-therapy nadir PSA (ptnPSA), when analyzed as continuous or
      categoric variables, predicted for BF (P<.001) and PCSS (P<.001). On multivariate
      analysis, nanPSA (P=.037) and ptnPSA (P<.001) continued to be significantly
      associated with BF. However, N-ADT duration lost significance (P=.67), and PSAHT
      remained a nonsignificant predictor (P=.97). For PCSS, multivariate analysis
      showed nanPSA (P=.049) and ptnPSA (P<.001) to be significant. Again PSAHT (P=.49)
      remained nonsignificant. CONCLUSIONS: In this large, prospective cohort of
      patients, NA PSA kinetics, expressed as PSAHT, did not predict BF or PCSS.
      However, nadir PSAs, in both the NA and post-therapy settings, were significant
      predictors of BF and PCSS. Optimization of therapy could potentially be based on
      early PSA response, with shorter durations of ADT for those predicted to do
      favorably, and intensification of therapy for those likely to have poorer
      outcomes.

PMID- 22652114
TI  - Impact of head trauma on pituitary function.
AB  - There have been in the past decade a growing number of studies relating head
      trauma to hypopituitarism. This condition may affect the rehabilitation process,
      and identification of such patients is therefore required. However, the widely
      different methods used so far for this purpose have provided inconsistent
      results. The incidence rate of hypopituitarism has probably been overestimated.
      This review focuses on the impact of head trauma on pituitary function, the
      diagnostic method, risk factors, and treatment options.

PMID- 22652113
TI  - Behavioral and neuroanatomical investigation of Highly Superior Autobiographical
      Memory (HSAM).
AB  - A single case study recently documented one woman's ability to recall accurately
      vast amounts of autobiographical information, spanning most of her lifetime,
      without the use of practiced mnemonics (Parker, Cahill, & McGaugh, 2006). The
      current study reports findings based on eleven participants expressing this same
      memory ability, now referred to as Highly Superior Autobiographical Memory
      (HSAM). Participants were identified and subsequently characterized based on
      screening for memory of public events. They were then tested for personal
      autobiographical memories as well as for memory assessed by laboratory memory
      tests. Additionally, whole-brain structural MRI scans were obtained. Results
      indicated that HSAM participants performed significantly better at recalling
      public as well as personal autobiographical events as well as the days and dates
      on which these events occurred. However, their performance was comparable to age-
      and sex-matched controls on most standard laboratory memory tests.
      Neuroanatomical results identified nine structures as being morphologically
      different from those of control participants. The study of HSAM may provide new
      insights into the neurobiology of autobiographical memory.

PMID- 22652115
TI  - The bitch uterine response to semen deposition and its modification by male
      accessory gland secretions.
AB  - Little is known about the response of the bitch's reproductive tract to semen
      deposition. In this study, an influx of polymorphonuclear neutrophils (PMNs) into
      the uterus was detected after artificial insemination, but there was normal
      fertility. Doppler ultrasonography showed that insemination induced an increase
      in uterine artery blood velocity and a decrease in the resistance index of short
      duration, indicating vasodilation. Semen that was extended in fluid from the
      sperm rich fraction of the ejaculate (seminal plasma, SP), or third fraction of
      the ejaculate (prostatic fluid, PF), produced a similar magnitude of effect but
      of longer duration. It was hypothesised that vasodilation following insemination
      was largely induced by SP and PF which, together with PMN influx, was part of a
      normal uterine response. Physiological concentrations of PMNs in vitro reduced
      the ability of spermatozoa to attach to uterine epithelium, most likely as a
      result of spermatozoa becoming attached to PMNs. However, both SP and PF
      increased attachment of spermatozoa to the uterine epithelium by reducing sperm
      attachment to PMNs, and potentially by an additional mechanism that did not
      involve inhibition of sperm binding to PMNs. These are the first canine studies
      to document an apparent physiological response by the uterus to semen, associated
      with uterine artery vasodilation and PMN influx. Moreover, these investigations
      are the first to demonstrate that canine SF and PF are part of the mechanism for
      increasing uterine perfusion and that both fluids have a modulatory effect on PMN
      induced inhibition of spermatozoal attachment to uterine epithelium, most likely
      mediated by reduced sperm attachment to PMNs.

PMID- 22652117
TI  - A preparation guide for surgical resident and student rotations to underserved
      regions.
AB  - Interest in global health among surgical residents and medical students is
      growing. There are numerous opportunities worldwide for both short- and long-term
      experiences. In order to maximize the learning potential, the authors present a
      practical guide for residents and students to prepare for a surgical visit,
      elective, rotation, or mission to an underserved region. The following steps will
      be outlined:

PMID- 22652116
TI  - [Schistosoma haematobium, a rare aetiology of spinal cord compression].
AB  - Human schistosomiasis is the second endemic disease after malaria. About 200
      millions people are concerned, particularly in Africa, South America and Asia.
      Schistosomal spinal cord compression is under reported in Africa and not well
      known. Authors present the case of a 10-year-old boy with no suggestive past
      medical story, admitted for spinal cord compression. MRI shows tumor like intra
      dural lesion. Schistosomal granuloma was found after lesion removal by posterior
      approach. Treatment was completed by praziquantel. Controversies of the treatment
      are presented.

PMID- 22652118
TI  - Can virtual reality simulation be used for advanced bariatric surgical training?
AB  - INTRODUCTION: Laparoscopic bariatric surgery is a safe and effective way of
      treating morbid obesity. However, the operations are technically challenging and
      training opportunities for junior surgeons are limited. This study aims to assess
      whether virtual reality (VR) simulation is an effective adjunct for training and
      assessment of laparoscopic bariatric technical skills. METHODS: Twenty bariatric
      surgeons of varying experience (Five experienced, five intermediate, and ten
      novice) were recruited to perform a jejuno-jejunostomy on both cadaveric tissue
      and on the bariatric module of the Lapmentor VR simulator (Simbionix Corporation,
      Cleveland, OH). Surgical performance was assessed using validated global rating
      scales (GRS) and procedure specific video rating scales (PSRS). Subjects were
      also questioned about the appropriateness of VR as a training tool for surgeons.
      RESULTS: Construct validity of the VR bariatric module was demonstrated with a
      significant difference in performance between novice and experienced surgeons on
      the VR jejuno-jejunostomy module GRS (median 11-15.5; P = .017) and PSRS (median
      11-13; P = .003). Content validity was demonstrated with surgeons describing the
      VR bariatric module as useful and appropriate for training (mean Likert score
      4.45/7) and they would highly recommend VR simulation to others for bariatric
      training (mean Likert score 5/7). Face and concurrent validity were not
      established. CONCLUSION: This study shows that the bariatric module on a VR
      simulator demonstrates construct and content validity. VR simulation appears to
      be an effective method for training of advanced bariatric technical skills for
      surgeons at the start of their bariatric training. However, assessment of
      technical skills should still take place on cadaveric tissue.

PMID- 22652119
TI  - Simulation-augmented training program for off-pump coronary artery bypass
      surgery: developing and validating performance assessments.
AB  - BACKGROUND: Simulation-based programs allow trainees to be progressively
      challenged in a systematic, learner-centered and patient-focused fashion. The
      design of these programs requires an understanding of the individual steps that
      comprise the entire surgical procedure and our ability to assess the progress of
      the learner. We present the results of the design and validation of performance
      assessment checklists for a progressive simulation-based program in cardiac
      surgery. METHODOLOGY: Using a case study design, we videotaped 10 off-pump
      coronary artery bypass procedures and applied a new methodological framework to
      deconstruct the procedure into teachable components for which 6 simulation
      scenarios were developed. Individual checklists were designed and validated using
      the Delphi technique. An expert panel of 11 cardiac surgeons rated each checklist
      item by using a 5-point Likert-type scale and provided comments on the rating
      choice. The consistency of the experts' ratings were interpreted as consensus
      achieved when 70% of experts rated 3.5 or greater on the 5-point Likert-type
      scale for each assessment item. RESULTS: An in vivo workflow diagram was
      developed, and 6 simulation modules with progressive difficulty were selected to
      design an off-pump coronary artery bypass simulation-based program. The
      corresponding 6 assessment checklists were designed and validated. After 2 Delphi
      rounds, the overall average score across all checklists was 4.0, and all items
      were greater 3.5. The final checklists comprise between 12 and 23 items.
      CONCLUSION: We have demonstrated the feasibility of designing simulation-based
      program for complex operative procedures in a progressive fashion. The complexity
      at each level was given by the predefined training objectives and assessment
      checklists were designed and validated as content-specific assessment tools for
      each simulation scenario.

PMID- 22652120
TI  - Can skills coaches be used to assess resident performance in the skills
      laboratory?
AB  - INTRODUCTION: The purpose of this study was to compare faculty ratings between
      live versus video-recorded resident performances and faculty versus skills
      coaches' ratings of video-recorded resident performances. METHODS: PGY1 residents
      were observed, video-recorded, and rated during a Verification of Proficiency
      examination on 4 stations (ie, suturing, laparotomy, central line, and
      cricothyroidotomy). One surgeon and 2 trained skills coaches independently rated
      each video-recorded performance (N = 25). The chi-square test was used to compare
      checklist ratings. Analysis of variance was used to compare global ratings.
      Intraclass correlations were used to evaluate inter-rater agreement. RESULTS:
      There were no statistical differences in faculty checklist ratings for live
      versus video-recorded performances (P > .05), and we found a nearly perfect
      interrater agreement, intraclass correlation coefficient (ICC) = 0.99 (P < .001).
      When comparing faculty versus skills coaches' ratings on video-recorded
      performances, we found no differences for the global or checklist ratings. Inter
      rater agreement was moderately high for the global ratings, ICC = 0.71 (P <.
      0.01, 95% confidence interval 0.23-0.96), and nearly perfect for the checklist
      ratings, ICC = 0.99 (P < .001, 95% confidence interval 0.94-1.00). CONCLUSION:
      When assessing residents' performances, use of video-recorded performance ratings
      and skills coaches may be viable alternatives to live ratings performed by
      surgical faculty.

PMID- 22652121
TI  - Orthopaedic Boot Camp II: examining the retention rates of an intensive surgical
      skills course.
AB  - BACKGROUND: We examined retention rates for basic surgical skills taught through
      a 1-month intensive laboratory boot camp-style course at the onset of residency.
      METHODS: We present data from 3 groups, each composed of 6 residents. The first
      group consisted of residents from a new competency-based curriculum (CBC). They
      started residency training with the Toronto Orthopaedic Boot Camp course. The
      other 2 groups were junior (JR) and senior (SR) residents from a traditional
      program whose residency training included no such course. Performance on targeted
      technical skills was tested using an objective structured assessment of technical
      skills examination 7 months after the onset of training for the CBC and JR groups
      and at least 43 months after the onset of training for the SR group. RESULTS: The
      mean global rating scale score for the CBC group immediately after the skills
      course was 4.3, which was maintained 6 months later. There were no significant
      performance differences between the CBC and SR groups. Both the CBC and SR groups
      performed significantly better than the JR group (mean global rating scale 3.7;
      F[2, 15] = 12.269, P < .001). CONCLUSION: We conclude that a surgical skills
      course at the onset of residency is an effective mechanism for teaching targeted
      technical skills and that skills taught in this manner can have excellent
      retention rates. Furthermore, an early focus on technical skills allows junior
      residents to perform at the same level as senior residents for certain tasks and
      may privilege later learning.

PMID- 22652122
TI  - A structured self-directed basic skills curriculum results in improved technical
      performance in the absence of expert faculty teaching.
AB  - BACKGROUND: We developed a novel curriculum teaching 20 open surgical skills in 5
      general domains (instrument handling, knot tying, simple wound closure, advanced
      wound closure, and hemostasis). The curriculum includes online didactics, skills
      practice, and defined performance metrics, but is entirely self-guided with no
      expert oversight or teaching. METHODS: Subjects included first- and second-year
      medical students (n = 9). Subjects first viewed a demonstration video depicting
      proper technique. The pretest was video-recorded performance of each skill.
      Subjects then completed the self-guided skills curriculum at their own pace,
      returning for posttesting once they met defined self-assessment criteria.
      Performance was evaluated through both self-assessment and blinded video review
      by 2 expert reviewers using previously validated scales. RESULTS: After
      completion of the curriculum, performance improved significantly by both self
      assessment (3,754 +/- 1,742 to 6,496 +/- 1,337; P < .01, Wilcoxon signed ranks)
      and expert assessment (10.1 +/- 2.6 to 14.6 +/- 2.7; P = .015). When analyzed by
      the 5 general domains, performance was significantly better for all domains by
      self-assessment (P < .05 for all domains) and in 4 domains by expert assessment
      (P < .04 for all domains other than instrument handling). CONCLUSION: Completion
      of a self-guided basic surgical skills curriculum allows novice learners to
      significantly improve performance in basic open surgical skills, without
      traditional expert teaching. This curriculum is useful for medical students and
      incoming junior residents.

PMID- 22652123
TI  - Residents' perspectives of the value of a simulation curriculum in a general
      surgery residency program: a multimethod study of stakeholder feedback.
AB  - BACKGROUND: Simulation has altered surgical curricula throughout residency
      programs. The purpose of this multimethod study was to explore residents'
      perceptions of simulation within surgical residency as relevant stakeholder
      feedback and program evaluation of the surgery simulation curriculum. METHODS:
      Focus groups were held with a sample of surgery residents (n = 25) at a
      university-affiliated program. Residents participated in focus groups based on
      level of training and completed questionnaires regarding simulation curricula.
      Groups were facilitated by nonsurgeon faculty. Residents were asked: "What is the
      role of simulation in surgical education?" An interdisciplinary team recorded
      narrative data and performed content analyses. Quantitative data from
      questionnaires were summarized using descriptive statistics and frequencies.
      RESULTS: Major themes from the qualitative data included: concerns regarding
      simulation in surgical education (28%), exposure to situations and technical
      skills in a low-stress learning environment (24%), pressure by external agencies
      (19%), an educational tool (17%), and quality assurance for patient care (12%).
      Laparoscopy and cadaver lab were the most prevalent simulation training during
      residency, in addition to trauma simulations, central lines/chest tubes/IV
      access, and stapling lab. In response to the statement: "ACGME should require a
      simulation curriculum in surgery residency," 52.1% responded favorably and 47.8%
      responded nonfavorably. CONCLUSION: Residents acknowledge the value of simulation
      in patient safety, quality, and exposure to procedures before clinical
      experience, but remain divided on efficacy and requirement of simulation within
      curricula. The greater challenge to residency programs may be strategic
      implementation of simulation curricula within the right training context.

PMID- 22652124
TI  - Economic effect of smoke-free ordinances on 11 Missouri cities.
AB  - INTRODUCTION: The harmful effects of secondhand smoke are convincing more and
      more communities across the United States and the world to prohibit smoking in
      public places, especially in eating and drinking establishments. A 1993 Missouri
      state law allows smoking in designated areas in indoor public places such as
      restaurants and bars. Consequently, some Missouri communities have adopted local
      ordinances that prohibit smoking in all indoor workplaces, including restaurants
      and bars. We used an objective measure of economic activity, the taxable sales
      revenues of eating and drinking establishments, to empirically examine the
      economic effect of smoke-free ordinances. METHODS: We studied the economic effect
      of smoke-free ordinances in 11 Missouri cities using multivariate log-linear
      regression models with log-transformed taxable sales revenues of eating and
      drinking establishments as the dependent variable and the smoke-free ordinance as
      the independent variable, while controlling for seasonality, economic condition
      and unemployment. We used data from 20 quarters before the smoke-free ordinances
      and at least 10 quarters after the smoke-free ordinances for all cities. The null
      hypothesis of no effect of smoke-free ordinance on taxable sales of the eating
      and drinking establishments was tested. RESULTS: Eight of the 11 cities had
      increased taxable sales for eating and drinking establishments postordinance. The
      remaining 3 experienced no change. CONCLUSION: The findings of our study are
      consistent with findings from most published economic studies that a smoke-free
      ordinance does not harm a local economy.

PMID- 22652125
TI  - South Asian American perspectives on overweight, obesity, and the relationship
      between weight and health.
AB  - INTRODUCTION: Compared with other racial groups, South Asian adults develop type
      2 diabetes and cardiovascular disease at a lower body mass index (BMI).
      Perceptions of weight and the effect of weight on health can influence weight
      loss attempts but are not well described in this population. The objective of
      this study was to examine perceptions of weight appropriateness and the effect of
      weight on health among South Asian Americans. METHODS: We recruited 75 South
      Asian American adults from a single metropolitan area in the Midwestern United
      States. During individual, face-to-face interviews, we asked participants what
      they think about their weight and how weight affects their health. We measured
      their weight and height and calculated BMI. Each interview was audiotaped,
      transcribed verbatim, and translated into English. We conducted analyses using
      NVivo software. A second investigator coded 20% of interviews to verify coding
      consensus. RESULTS: Sixty-seven percent of participants were overweight or obese;
      40% of overweight participants and 12% of obese participants perceived themselves
      to be normal weight or underweight. Forty-eight percent of overweight and 82% of
      obese participants believed their weight affected their health. Participants
      commonly cited physical problems as being associated with their weight, but few
      connected their weight with risk for chronic diseases. CONCLUSION: South Asian
      Americans may underestimate their weight status and the effect of their weight on
      their risk for chronic diseases. Interventions to promote weight loss among South
      Asian Americans should focus on modifying perceptions of normal weight and
      personalizing the relationship between overweight and chronic diseases.

PMID- 22652126
TI  - Health-related quality of life among US veterans and civilians by race and
      ethnicity.
AB  - INTRODUCTION: Among veterans, having been selected into the military and having
      easy access to medical care during and after military service may reduce
      premature mortality but not morbidity from mental distress and may not improve
      health-related quality of life. The objective of this study was to determine
      whether veterans in different racial/ethnic groups differ in their health-related
      quality of life from each other and from their civilian counterparts. METHODS:
      Among 800,000 respondents to the 2007-2009 Behavioral Risk Factor Surveillance
      System surveys, approximately 110,000 identified themselves as veterans and
      answered questions about their sociodemographic characteristics, self-rated
      health, and recent health-related quality of life. Nonoverlapping 95% confidence
      intervals of means distinguished veterans and civilians of different
      racial/ethnic groups. RESULTS: Veteran and civilian American Indians/Alaska
      Natives reported more physically unhealthy days, mentally unhealthy days, and
      recent activity limitation days than their veteran and civilian counterparts in
      other racial/ethnic groups. Non-Hispanic white veterans and Hispanic veterans
      reported more physically unhealthy days, mentally unhealthy days, and recent
      activity limitation days than their civilian counterparts. CONCLUSION: Unlike
      findings in other studies, our findings show that veterans' health-related
      quality of life differs from that of civilians both within the same racial/ethnic
      group and among different racial/ethnic groups. Because once-healthy soldiers may
      not be as healthy when they return to civilian life, assessing their health
      related quality of life over time may identify those who need help to regain
      their health.

PMID- 22652127
TI  - Paxillus involutus strains MAJ and NAU mediate K(+)/Na(+) homeostasis in
      ectomycorrhizal Populus x canescens under sodium chloride stress.
AB  - Salt-induced fluxes of H(+), Na(+), K(+), and Ca(2+) were investigated in
      ectomycorrhizal (EM) associations formed by Paxillus involutus (strains MAJ and
      NAU) with the salt-sensitive poplar hybrid Populus * canescens. A scanning ion
      selective electrode technique was used to measure flux profiles in non-EM roots
      and axenically grown EM cultures of the two P. involutus isolates to identify
      whether the major alterations detected in EM roots were promoted by the fungal
      partner. EM plants exhibited a more pronounced ability to maintain K(+)/Na(+)
      homeostasis under salt stress. The influx of Na(+) was reduced after short-term
      (50 mm NaCl, 24 h) and long-term (50 mm NaCl, 7 d) exposure to salt stress in
      mycorrhizal roots, especially in NAU associations. Flux data for P. involutus and
      susceptibility to Na(+)-transport inhibitors indicated that fungal colonization
      contributed to active Na(+) extrusion and H(+) uptake in the salinized roots of
      P. * canescens. Moreover, EM plants retained the ability to reduce the salt
      induced K(+) efflux, especially under long-term salinity. Our study suggests that
      P. involutus assists in maintaining K(+) homeostasis by delivering this nutrient
      to host plants and slowing the loss of K(+) under salt stress. EM P. * canescens
      plants exhibited an enhanced Ca(2+) uptake ability, whereas short-term and long
      term treatments caused a marked Ca(2+) efflux from mycorrhizal roots, especially
      from NAU-colonized roots. We suggest that the release of additional Ca(2+)
      mediated K(+)/Na(+) homeostasis in EM plants under salt stress.

PMID- 22652129
TI  - Anticoagulant activity of Moon jellyfish (Aurelia aurita) tentacle extract.
AB  - Moon jellyfish (Aurelia aurita) tentacle extract was studied for its
      anticoagulant activity in vitro. The Jellyfish Tentacle Extract (JFTE) showed
      very strong fibrinogenolytic activity by cleaving Aalpha and Bbeta chain of
      fibrinogen molecule. The fibrinogenolytic activity was found to be stronger than
      some snake venom derived anticoagulants. JFTE also completely liquefied fibrin
      clots in 24 h. JFTE was found to contain both high and low molecular weight
      proteins/peptides. The fibrinogenolysis appears to be caused by high molecular
      weight fractions of the extract. It has been also noted that PMSF significantly
      reduced fibrinogenolytic activity and heating totally abolished it. Autolytic
      degradation of the high molecular weight protein was also noted. Autolysis slowed
      down, but did not abolish the fibrinogenolytic activity of the extract.

PMID- 22652128
TI  - Transcriptional responses toward diffusible signals from symbiotic microbes
      reveal MtNFP- and MtDMI3-dependent reprogramming of host gene expression by
      arbuscular mycorrhizal fungal lipochitooligosaccharides.
AB  - The formation of root nodules and arbuscular mycorrhizal (AM) roots is controlled
      by a common signaling pathway including the calcium/calmodulin-dependent kinase
      Doesn't Make Infection3 (DMI3). While nodule initiation by
      lipochitooligosaccharide (LCO) Nod factors is well characterized, diffusible AM
      fungal signals were only recently identified as sulfated and nonsulfated LCOs.
      Irrespective of different outcomes, the perception of symbiotic LCOs in Medicago
      truncatula is mediated by the LysM receptor kinase M. truncatula Nod factor
      perception (MtNFP). To shed light on transcriptional responses toward symbiotic
      LCOs and their dependence on MtNFP and Ca(2+) signaling, we performed genome-wide
      expression studies of wild-type, Nod-factor-perception mutant1, and dmi3 mutant
      roots challenged with Myc- and Nod-LCOs. We show that Myc-LCOs lead to transient,
      quick responses in the wild type, whereas Nod-LCOs require prolonged incubation
      for maximal expression activation. While Nod-LCOs are most efficient for an
      induction of persistent transcriptional changes, sulfated Myc-LCOs are less
      active, and nonsulfated Myc-LCOs display the lowest capacity to activate and
      sustain expression. Although all symbiotic LCOs up-regulated a common set of
      genes, discrete subsets were induced by individual LCOs, suggesting common and
      specific functions for these in presymbiotic signaling. Surprisingly, even
      sulfated fungal Myc-LCOs and Sinorhizobium meliloti Nod-LCOs, having very similar
      structures, each elicited discrete subsets of genes, while a mixture of both Myc
      LCOs activated responses deviating from those induced by single treatments.
      Focusing on the precontact phase, we identified signaling-related and
      transcription factor genes specifically up-regulated by Myc-LCOs. Comparative
      gene expression studies in symbiotic mutants demonstrated that transcriptional
      reprogramming by AM fungal LCOs strictly depends on MtNFP and largely requires
      MtDMI3.

PMID- 22652130
TI  - On the performance qualification of hypromellose capsules.

PMID- 22652131
TI  - [Vacuum assisted closure in open abdomen and deferred closure: experience in 23
      patients].
AB  - INTRODUCTION: We analyse our experience and the results obtained with the use of
      vacuum assisted closure (VAC((r)), KCI Clinic Spain SL) in the management of open
      abdomen. MATERIAL AND METHODS: We retrospectively reviewed the laparostomies
      performed between June 2006 and March 2011 using VAC((r)) treatment in the
      Hospital Xeral-Cies, Vigo. RESULTS: We included 23 consecutive patients (18 males
      and 5 females) on whom the VAC((r)) was used in the open abdomen due to different
      indications (abdominal trauma, peritonitis, pancreatitis, ischaemic disease or
      abdominal compartmental syndrome). The VAC((r)) needed changing a mean of 3.1
      times per patient (range 1-7), with total mean treatment duration of 14.8 days (2
      43) until closure, primary closure being achieved in 18 out of 21 patients (86%).
      The mean hospital stay was 110.1 days (8-163) and 6 patients (26%) died during
      their hospital stay due to problems related to their underlying disease. Seven
      cases (30%) had complications during the VAC(r) therapy: 3 intra-abdominal
      abscesses (13%), 4 fistulas or suture dehiscence (17%), and 1 evisceration (4%).
      CONCLUSIONS: VAC((r)) therapy is simple to manage, with an acceptable rate of
      complication, particularly of intestinal fistulas, and a reduced mortality. Of
      the various systems available for the deferred closure of the abdomen, the
      VAC((r)) has made considerable progress in the past few years, mainly due to its
      adaptable material, and its numerous advantages. Its use will possibly increase
      in the future.

PMID- 22652134
TI  - The practice of continuous deep sedation until death in Flanders (Belgium), the
      Netherlands, and the U.K.: a comparative study.
AB  - CONTEXT: Existing empirical evidence shows that continuous deep sedation until
      death is given in about 15% of all deaths in Flanders, Belgium (BE), 8% in The
      Netherlands (NL), and 17% in the U.K. OBJECTIVES: This study compares
      characteristics of continuous deep sedation to explain these varying frequencies.
      METHODS: In Flanders, BE (2007) and NL (2005), death certificate studies were
      conducted. Questionnaires about continuous deep sedation and other decisions were
      sent to the certifying physicians of each death from a stratified sample
      (Flanders, BE: n=6927; NL: n=6860). In the U.K. in 2007-2008, questionnaires were
      sent to 8857 randomly sampled physicians asking them about the last death
      attended. RESULTS: The total number of deaths studied was 11,704 of which 1517
      involved continuous deep sedation. In Dutch hospitals, continuous deep sedation
      was significantly less often provided (11%) compared with hospitals in Flanders,
      BE (20%) and the U.K. (17%). In U.K. home settings, continuous deep sedation was
      more common (19%) than in Flanders, BE (10%) or NL (8%). In NL in both settings,
      continuous deep sedation more often involved benzodiazepines and lasted less than
      24 hours. Physicians in Flanders combined continuous deep sedation with a
      decision to provide physician-assisted death more often. Overall, men, younger
      patients, and patients with malignancies were more likely to receive continuous
      deep sedation, although this was not always significant within each country.
      CONCLUSION: Differences in the prevalence of continuous deep sedation appear to
      reflect complex legal, cultural, and organizational factors more than differences
      in patients' characteristics or clinical profiles. Further in-depth studies
      should explore whether these differences also reflect differences between
      countries in the quality of end-of-life care.

PMID- 22652133
TI  - Causal attributions for fatigue by older adults with advanced cancer.
AB  - CONTEXT: Fatigue is a prevalent, debilitating, and often disruptive symptom for
      cancer patients. Yet, it remains inadequately understood and managed, especially
      among late middle-aged and older patients with advanced disease. Few studies have
      explored fatigue qualitatively, and almost none have focused on patients'
      attributions for this subjective and multidimensional symptom. OBJECTIVES: Our
      objectives were to 1) examine the attributions patients aged 55 years or older
      with advanced cancer made for their fatigue and how they arrived at these
      attributions and 2) understand how patients' attributions affect how they contend
      with fatigue, including communication with health care providers. METHODS: We
      conducted qualitative in-depth interviews with 35 patients aged 55 years or older
      on their experiences with fatigue. Patients had a variety of cancers and were at
      stages IV or late III of the disease. Interviews were thematically coded and
      analyzed. RESULTS: Two main themes emerged: 1) Cancer-related treatment was the
      master and often the sole attribution patients made for their fatigue. Patients
      making this attribution expressed certainty about its accuracy and seemed less
      distressed about the symptom. 2) Multiple causes of fatigue, typically a
      combination of cancer, treatment, and nonthreatening causes (e.g., older age,
      overexertion, or anemia), also were offered by some. Patients seemed to resist
      identifying disease severity as a cause and appeared motivated to normalize and
      minimize the symptom, thus decreasing its threatening impact. CONCLUSION:
      Patients' causal attributions for fatigue had a profound effect on their physical
      and psychological well-being, their communication with providers, and their
      integration of the symptom into their lives.

PMID- 22652135
TI  - Direct observation of prognosis communication in palliative care: a descriptive
      study.
AB  - CONTEXT: Palliative care (PC) consultations result in improved patient
      understanding of prognosis and better quality of life, yet the content and
      processes of prognosis communication during PC consultations remain unknown.
      OBJECTIVES: To describe prognosis communication during PC consultation with
      seriously ill hospitalized patients. METHODS: We audio recorded 71 sequential
      inpatient PC consultations (initial visit) with seriously ill patients and their
      families who were referred for "goals of care" clarification or help with "end-of
      life decision making." Conversations were coded using reliable methods and we
      then linked conversation codes to clinical record and clinician interview data.
      RESULTS: Ninety-three percent of consultations contained prognosis communication.
      Participants communicated prognoses regarding quality of life more frequently
      than survival; focused prognosis estimates on the unique patient more frequently
      than on a general population; and framed prognosis using pessimistic cues more
      frequently than optimistic ones. Prognoses were more commonly spoken by PC
      clinicians than by patients/families. The following two factors demonstrated an
      association with the rate of prognostic communication and with the pessimistic
      framing of that information: whether the patient, family, or both participated in
      the conversation, and shorter expected survival (as estimated by the attending
      physician). CONCLUSION: Prognoses are routinely communicated in PC consultations
      with hospitalized patients and their families. The rate and characteristics of
      prognosis communication differ based on the length of time the patient is
      expected to live.

PMID- 22652137
TI  - Assessing the diagnostic accuracy (DA) of the Spanish version of the informant
      based AD8 questionnaire.
AB  - INTRODUCTION: The AD8 is a brief informant-based questionnaire that may also be
      self-administered, and which aids in identifying cognitive impairment (CI). Our
      goal is to assess the diagnostic accuracy (DA) of a Spanish version of that
      questionnaire. MATERIAL AND METHODS: Cross-sectional study of a clinical sample
      of patient/informant dyads including 330 subjects with suspected CI or dementia
      (DEM) and 71 controls. We evaluated internal consistency (Cronbach's alpha) and
      validity (partial correlations with GDS stage, Fototest results and functional
      index measure [FIM]). We assessed DA for CI vs no CI (GDS stage 3-4) using the
      area under the ROC curve (AUC), and the cut-off with the highest Youden index was
      determined to be optimal. RESULTS: In the sample, 105 subjects had no CI, 99 had
      CI without DEM and 203 had DEM. Internal consistency was high (alpha 0.90, 95%
      confidence interval: 0.89-0.92), as were correlations with the GDS score (r=0.72,
      P<.001), Fototest results (r=-0.61, P<.001) and FIM (r=0.59, P<.001). The AUC for
      AD8 was 0.90 (95% confidence interval: 0.86-0.93), which was not significantly
      different from that of the Fototest (AUC 0.93, 95% confidence interval: 0.89
      0.96). The optimal cut-off point was 3/4 with a sensitivity of 0.93 (95%
      confidence interval: 0.88-0.96) and a specificity of 0.81 (95% confidence
      interval: 0.72-0.88); 88.8% of the classifications were correct. Combined use of
      AD8 and the Fototest significantly improved the DA of both (AUC 0.96, 95%
      confidence interval: 0.93-0.98, P<.05). CONCLUSIONS: The Spanish version of the
      AD8 questionnaire preserves the psychometric qualities and DA of the original.
      Using this test in combination with the Fototest significantly increases the DA
      of both tests.

PMID- 22652136
TI  - A successful palliative care intervention for cancer pain refractory to
      intrathecal analgesia.
AB  - Intrathecal delivery of opioid medications has been increasingly used to treat
      cancer pain that is refractory to conventional oral opioid therapy. We present a
      patient with complex and refractory cancer pain who failed both oral and
      intrathecal opioid therapy but responded to the interdisciplinary palliative care
      intervention in the acute palliative care unit. His morphine equivalent daily
      dose decreased by 94% over a 10-day period, and he had better pain control and
      improved function. This case highlights the importance of addressing and treating
      the psychosocial distress that contributes to the total pain expression.

PMID- 22652138
TI  - Spanish normative studies in young adults (NEURONORMA young adults project):
      norms for Stroop Color-Word Interference and Tower of London-Drexel University
      tests.
AB  - INTRODUCTION: The Stroop Color-Word Interference Test (Stroop) measures cognitive
      flexibility, selective attention, cognitive inhibition and information processing
      speed. The Tower of London-Drexel University version test (TOL) assesses higher
      order problem solving and executive planning abilities. OBJECTIVE: In this study,
      as part of the Spanish normative studies project in young adults (NEURONORMA
      young adults), we present normative data for the Stroop and young adults TOL
      tests. MATERIAL AND METHODS: The sample consisted of 179 participants who are
      cognitively normal and range in age from 18 to 49 years. Tables are provided to
      convert raw scores to scaled scores. Scores adjusted for sociodemographic factors
      were obtained by applying linear regression techniques. RESULTS: No effects were
      found for age and sex in either test. Educational level impacted most of the
      Stroop test variables and some of the TOL scores (Total Moves score and Total
      Initiation Time score). CONCLUSIONS: The norms obtained will be extremely useful
      in the clinical evaluation of young Spanish adults.

PMID- 22652139
TI  - Blepharospasm and hemifacial spasm: long-term treatment with botulinum toxin.
AB  - INTRODUCTION: Our purpose is to describe the demographic, clinical and
      therapeutic characteristics of patients with blepharospasm (BS) and hemifacial
      spasm (HFS) in treatment with botulinum toxin type A (BtA). PATIENTS AND METHODS:
      Retrospective analysis of patients diagnosed with BS or HFS and treated with BtA
      in the Neurology Department at Complejo Asistencial de Segovia between March 1991
      and December 2009. RESULTS: Different variables were collected from 34 patients
      with BS and 55 with HFS, of whom 44.1% and 32.7% respectively had been undergoing
      treatment with BtA for more than 10 years. Elapsed time from symptom onset to the
      first visit was 24 months in the BS group and 59.7 months in the HFS group.
      Diagnosis was given on the first visit for 76.5% of the BS patients and 90.7% of
      the HFS patients. Patients were referred by their primary care centres in 34.6%
      of the cases with BS and in 77.6% of the cases with HFS. The most commonly used
      BtA preparation was BOTOX((r)) in both groups, and there were no cases of primary
      or secondary resistance. The median dose of BtA was raised gradually in both
      groups, and the increase was statistically significant during the early years of
      treatment. The most common side effect was ptosis (47.1% in BS, 32.5% in HFS).
      CONCLUSIONS: BS and HFS are the most common facial movement disorders. The
      demographic and clinical characteristics and therapeutic findings from this study
      show that treatment with BtA is both effective and safe over the long term.

PMID- 22652140
TI  - Spanish normative studies in young adults (NEURONORMA young adults project):
      norms for the Rey-Osterrieth Complex Figure (copy and memory) and Free and Cued
      Selective Reminding Test.
AB  - INTRODUCTION: The Rey-Osterrieth Complex Figure (ROCF) and the Free and Cued
      Selective Reminding Test (FCSRT) are widely used in clinical practice. The ROCF
      assesses visual perception, constructional praxis, and visuo-spatial memory. The
      FCSRT assesses verbal learning and memory. OBJECTIVE: In this study, as part of
      the Spanish normative studies project in young adults (NEURONORMA young adults),
      we present age- and education-adjusted normative data for both tests obtained by
      using linear regression techniques. MATERIAL AND METHODS: The sample consisted of
      179 healthy participants ranging in age from 18 to 49 years. We provide tables
      for converting raw scores to scaled scores in addition to tables with scores
      adjusted by socio-demographic factors. RESULTS: The results showed that education
      affects scores for some of the memory tests and the figure-copying task. Age was
      only found to have an effect on the performance of visuo-spatial memory tests,
      and the effect of sex was negligible. CONCLUSIONS: The normative data obtained
      will be extremely useful in the clinical neuropsychological evaluation of young
      Spanish adults.

PMID- 22652142
TI  - Critical stenosis of the basilar artery associated with clinical instability: new
      proposed indication for acute endovascular treatment.

PMID- 22652141
TI  - Spanish normative studies in young adults (NEURONORMA young adults project):
      norms for verbal fluency tests.
AB  - INTRODUCTION: Lexical fluency tests are frequently used in clinical practice to
      assess language and executive function. OBJECTIVE: As part of the Spanish
      normative studies project in young adults (NEURONORMA young adults project), we
      provide age- and education-adjusted normative data for 3 semantic fluency tasks
      (animals, fruits and vegetables, and kitchen tools), three formal lexical fluency
      tasks (words beginning with P, M and R), three excluded-letter fluency tasks
      (words excluding A, E and S) and a verb fluency task. MATERIAL AND METHODS: The
      sample consisted of 179 participants who are cognitively normal and range in age
      from 18 to 49 years. Tables are provided to convert raw scores to scaled scores.
      Age- and education-adjusted scores are provided by applying linear regression
      techniques. RESULTS: The results show that education impacted most of the verbal
      fluency test scores, with no effects related to age and only minimal effects
      related to sex. CONCLUSIONS: The norms obtained will be extremely useful in the
      clinical evaluation of young Spanish adults.

PMID- 22652143
TI  - Spanish normative studies in young adults (NEURONORMA young adults project):
      norms for the Visual Object and Space Perception Battery and Judgment of Line
      Orientation tests.
AB  - INTRODUCTION: The Visual Object and Space Perception Battery (VOSP) and Judgment
      of Line Orientation tests (JLO) are used in clinical practice to assess
      visuoperceptual and visuospatial abilities. OBJECTIVE: In this study, as part of
      the Spanish normative studies project in young adults (NEURONORMA young adults),
      we present normative data for a short version of the VOSP test and for the JLO
      test. MATERIAL AND METHODS: The sample consisted of 179 participants who are
      cognitively normal and range in age from 18 to 49 years. Tables are provided to
      convert raw scores to scaled scores. Education- and sex-adjusted scores were
      obtained by applying linear regression techniques. RESULTS: Our results show that
      education and sex only affect scores on the JLO test, and that age has no effect.
      CONCLUSIONS: The normative data obtained will be extremely useful in the clinical
      evaluation of young Spanish adults.

PMID- 22652144
TI  - [Intravenous thrombolysis in capsular warning syndrome: is it beneficial?].

PMID- 22652145
TI  - Visual form-processing deficits: a global clinical classification.
AB  - INTRODUCTION: Patients who have difficulties recognising visual form stimuli are
      usually labelled as having visual agnosia. However, recent studies let us
      identify different clinical manifestations corresponding to discrete diagnostic
      entities which reflect a variety of deficits along the continuum of cortical
      visual processing. DEVELOPMENT: We reviewed different clinical cases published in
      medical literature as well as proposals for classifying deficits in order to
      provide a global perspective of the subject. Here, we present the main findings
      on the neuroanatomical basis of visual form processing and discuss the criteria
      for evaluating processing which may be abnormal. We also include an inclusive
      diagram of visual form processing deficits which represents the different
      clinical cases described in the literature. Lastly, we propose a boosted decision
      tree to serve as a guide in the process of diagnosing such cases. CONCLUSIONS:
      Although the medical community largely agrees on which cortical areas and
      neuronal circuits are involved in visual processing, future studies making use of
      new functional neuroimaging techniques will provide more in-depth information. A
      well-structured and exhaustive assessment of the different stages of visual
      processing, designed with a global view of the deficit in mind, will give a
      better idea of the prognosis and serve as a basis for planning personalised
      psychostimulation and rehabilitation strategies.

PMID- 22652146
TI  - Evaluating the influence of different modes of administration of a pre-exercise
      screening tool.
AB  - OBJECTIVES: Exercise participation is important in overall health, but is not
      without risk, particularly when exercising at vigorous intensities. Pre-exercise
      screening procedures such as the Sports Medicine Australia Pre-Exercise Screening
      System (SMA PESS) aim to minimise risks while maximising benefits from physical
      activity. The purpose of this study was to evaluate the SMA PESS as it might be
      used within commercial fitness centres and to determine the effect of point of
      care blood analysis on risk identification. DESIGN: Convenience sample of
      participants attending fitness centres for exercise classes. METHODS:
      Participants were recruited from commercial fitness centres and completed the
      PESS via self-administration and interview with an Exercise & Sports Science
      Australia Accredited Exercise Physiologist. Blood related risk factors obtained
      from the CardioChek((r)) point of care blood analyser were compared to those
      obtained from laboratory analysis. RESULTS: Findings indicated that approximately
      54% of participants would be required to seek medical clearance with a further
      17% restricted to moderate intensity exercise. The identification of risk in
      Stage 2 of the SMA PESS improved with increasing rigour of application, with the
      number of participants classified as moderate risk increasing non-significantly
      from 37% to 50% (p=0.40). CONCLUSIONS: Increasing the rigour of administration of
      the SMA PESS influences risk identification and results in a higher number of
      clients being excluded from participation in vigorous intensity exercise.

PMID- 22652147
TI  - Comparison of plantar loads during treadmill and overground running.
AB  - OBJECTIVES: The objective of this study is to compare plantar loads during
      treadmill running and running on concrete and grass surfaces. DESIGN: Crossover
      study design was used in the study. METHODS: A total of 16 experienced heel-to
      toe runners participated in the study. Plantar loads data were collected using a
      Novel Pedar insole sensor system during running on the treadmill, concrete, and
      grass surfaces at 3.8m/s running speed and then analyzed. RESULTS: Compared with
      running on the two other surfaces, treadmill running showed a lower magnitude of
      maximum plantar pressure and maximum plantar force for the total foot, maximum
      plantar pressure at two toe regions, and maximum plantar force for the medial
      forefoot region and two toe regions (p<0.0017). Treadmill running also showed a
      longer absolute contact time at two toe regions compared with running on the
      other two surfaces (p<0.0017). CONCLUSIONS: Treadmill running is associated with
      a lower magnitude of maximum plantar pressure and a lower maximum plantar force
      at the plantar areas. These results suggest that the plantar load distribution in
      treadmill running is not the same as the plantar load distribution in running on
      overground surfaces. Treadmill running may be useful in early rehabilitation
      programs. Patients with injuries in their lower extremities may benefit from the
      reduction in plantar loads. However, the translation to overground running needs
      investigation.

PMID- 22652148
TI  - TIMP-1/-2 and transient elastography allow non invasive diagnosis of cystic
      fibrosis associated liver disease.
AB  - BACKGROUND: Cystic fibrosis (CF) associated liver disease develops in
      approximately 30% of CF patients. However, routine sensitive diagnostic tools are
      lacking. AIMS: We aimed to compare the value of transient elastography and
      experimental fibrosis markers for the detection of liver disease in CF patients.
      METHODS: 145 CF patients (75 children, 70 adults) were prospectively studied and
      received transient elastography. CF liver disease was diagnosed according to
      recent guidelines. Serum concentrations of YKL-40, HA, PIIIP, MMP-9, TIMP-1 and
      TIMP-2 were determined by ELISA. RESULTS: Transient elastography was increased in
      adults and children with CF hepatopathy compared to those without and exhibited a
      high diagnostic accuracy for CF liver disease. In adults with portal
      hypertension, elastography was further enhanced. TIMP-2 was elevated in adults
      with CF hepatopathy associated portal hypertension and exhibited a high
      diagnostic accuracy for portal hypertension in adults and for CF hepatopathy in
      children. TIMP-1 had a high diagnostic accuracy for CF hepatopathy in adults.
      Diagnostic sensitivities were increased when elastography and respective
      biomarkers were combined for the detection of CF hepatopathy and portal
      hypertension. CONCLUSIONS: TIMP-1 and TIMP-2 represent powerful biomarkers for CF
      associated liver disease and portal hypertension. Their determination may confirm
      and improve the diagnostic accuracy of transient elastography.

PMID- 22652149
TI  - Ceramide biosynthesis and metabolism in trophoblast syncytialization.
AB  - Sphingolipid mediators such as ceramide are pleiotropic regulators of cellular
      growth, differentiation and apoptosis. We investigated the role of ceramide
      biosynthesis, metabolism and actions in term human cytotrophoblasts syncytialized
      over 7 days in culture. Intracellular C16 ceramide levels increased modestly
      after 3 days in culture, then declined. Ceramidase was present at particularly
      high levels in syncytialized trophoblasts; inhibition of ceramidase reduced the
      degree of cell fusion. Exposure to short chain C8 ceramide or aSMase enhanced
      secretion of the differentiation marker hCG without affecting fusion or cell
      viability. In contrast, pharmacological inhibition of ceramidase reduced the
      extent of fusion. Inhibition of the ceramide-responsive JNK and PP2A pathways did
      not abolish the effects of ceramide, and JNK phosphorylation was unresponsive to
      ceramide; however, ceramide significantly inhibited phosphorylation of Akt. This
      study suggests that changes in ceramide biosynthesis and metabolism play a
      differential role in the biochemical and morphological features of trophoblast
      differentiation.

PMID- 22652150
TI  - Identification of gene clusters associated with fusaric acid, fusarin, and
      perithecial pigment production in Fusarium verticillioides.
AB  - The genus Fusarium is of concern to agricultural production and food/feed safety
      because of its ability to cause crop disease and to produce mycotoxins.
      Understanding the genetic basis for production of mycotoxins and other secondary
      metabolites (SMs) has the potential to limit crop disease and mycotoxin
      contamination. In fungi, SM biosynthetic genes are typically located adjacent to
      one another in clusters of co-expressed genes. Such clusters typically include a
      core gene, responsible for synthesis of an initial chemical, and several genes
      responsible for chemical modifications, transport, and/or regulation. Fusarium
      verticillioides is one of the most common pathogens of maize and produces a
      variety of SMs of concern. Here, we employed whole genome expression analysis and
      utilized existing knowledge of polyketide synthase (PKS) genes, a common cluster
      core gene, to identify three novel clusters of co-expressed genes in F.
      verticillioides. Functional analysis of the PKS genes linked the clusters to
      production of three known Fusarium SMs, a violet pigment in sexual fruiting
      bodies (perithecia) and the mycotoxins fusarin C and fusaric acid. The results
      indicate that microarray analysis of RNA derived from culture conditions that
      induce differential gene expression can be an effective tool for identifying SM
      biosynthetic gene clusters.

PMID- 22652151
TI  - Expression of minichromosome maintenance 2, Ki-67, and geminin in oral nevi and
      melanoma.
AB  - Evaluation of cell cycle using antibodies against nuclear proteins involved in
      regulating DNA replication has gained special interest in the effort to predict
      biologic behavior of benign and malignant tumors. The aim of this study was to
      analyze the expression of minichromosome maintenance 2, Ki-67, and geminin in
      oral nevi and melanomas. Expression of these cell proliferation markers was
      evaluated by immunohistochemistry in 49 oral melanocytic lesions, including 38
      intramucosal nevi and 11 primary oral melanomas. The labeling index of each
      proliferation marker was assessed considering the percentage of cells expressing
      nuclear positivity out of the total number of cells, counting 1000 cells per
      slide. Minichromosome maintenance 2, Ki-67, and geminin were rarely expressed in
      intramucosal nevi, in contrast to oral melanomas, which showed high levels of
      these cell proliferation markers, particularly minichromosome maintenance 2,
      indicating it is a more sensitive marker in primary oral melanomas than Ki-67 and
      geminin. These results indicate that these markers may be involved in the
      pathogenesis of oral melanomas and could be eventually useful as an additional
      diagnostic tool for differential diagnosis of oral benign and malignant
      melanocytic lesions.

PMID- 22652153
TI  - Robust closed-loop minimal sampling method for HIV therapy switching strategies.
AB  - The emergence of drug-resistant strains of human immunodeficiency virus during
      antiretroviral therapy is a major cause of treatment failure and disease
      progression. Development of a resistant strain necessitates switching to a new
      antiretroviral regimen composed of novel drugs. Recent work has shown that
      current methods of switching antiviral therapies carry significant unnecessary
      risk of subsequent failures, and optimal switching schedules to minimize this
      risk have been proposed. These switching schedules require frequent sampling of
      viral load during an induced phase of transient viral load reduction, with the
      goal of switching to the new antiviral regimen at an induced viral load minimum.
      The proposed frequent sampling carries an unacceptable level of cost both in
      terms of measurement expense and inconvenience to the patient. In this paper, we
      propose a closed-loop sampling algorithm to reduce the number of samples required
      to achieve the desired reduction in risk. We demonstrate through the Monte-Carlo
      analysis that the proposed method is able to robustly achieve an average 50%
      reduction in the number of required samples while maintaining a reduction in the
      risk of subsequent failure to under 3%, despite experimentally verified levels of
      model and measurement uncertainty.

PMID- 22652152
TI  - Potential impact of adding genetic markers to clinical parameters in predicting
      prostate biopsy outcomes in men following an initial negative biopsy: findings
      from the REDUCE trial.
AB  - BACKGROUND: Several germline single nucleotide polymorphisms (SNPs) have been
      consistently associated with prostate cancer (PCa) risk. OBJECTIVE: To determine
      whether there is an improvement in PCa risk prediction by adding these SNPs to
      existing predictors of PCa. DESIGN, SETTING, AND PARTICIPANTS: Subjects included
      men in the placebo arm of the randomized Reduction by Dutasteride of Prostate
      Cancer Events (REDUCE) trial in whom germline DNA was available. All men had an
      initial negative prostate biopsy and underwent study-mandated biopsies at 2 yr
      and 4 yr. Predictive performance of baseline clinical parameters and/or a genetic
      score based on 33 established PCa risk-associated SNPs was evaluated. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Area under the receiver operating
      characteristic curves (AUC) were used to compare different models with different
      predictors. Net reclassification improvement (NRI) and decision curve analysis
      (DCA) were used to assess changes in risk prediction by adding genetic markers.
      RESULTS AND LIMITATIONS: Among 1654 men, genetic score was a significant
      predictor of positive biopsy, even after adjusting for known clinical variables
      and family history (p = 3.41 * 10(-8)). The AUC for the genetic score exceeded
      that of any other PCa predictor at 0.59. Adding the genetic score to the best
      clinical model improved the AUC from 0.62 to 0.66 (p<0.001), reclassified PCa
      risk in 33% of men (NRI: 0.10; p=0.002), resulted in higher net benefit from DCA,
      and decreased the number of biopsies needed to detect the same number of PCa
      instances. The benefit of adding the genetic score was greatest among men at
      intermediate risk (25th percentile to 75th percentile). Similar results were
      found for high-grade (Gleason score >= 7) PCa. A major limitation of this study
      was its focus on white patients only. CONCLUSIONS: Adding genetic markers to
      current clinical parameters may improve PCa risk prediction. The improvement is
      modest but may be helpful for better determining the need for repeat prostate
      biopsy. The clinical impact of these results requires further study.

PMID- 22652154
TI  - MGST1 expression in serous ovarian carcinoma differs at various anatomic sites,
      but is unrelated to chemoresistance or survival.
AB  - OBJECTIVE: To investigate the expression of MGST1 in primary tumors, solid
      metastases and metastatic effusions in advanced-stage serous ovarian carcinoma
      (OC) and analyze the association with clinicopathologic parameters, including
      chemotherapy resistance and survival. METHODS: MGST1 mRNA expression was
      investigated in 178 tumors (88 effusions, 38 primary carcinomas, 52 solid
      metastases) from 144 patients using real-time quantitative PCR (qRT-PCR). Forty
      two of the 88 effusions were additionally analyzed for MGST1 protein expression
      by Western blotting. RESULTS: mRNA expression of MGST1 was higher in primary
      carcinomas and solid metastases compared to effusions (p=0.008 and p=0.012,
      respectively). In patient-matched samples, mRNA expression of MGST1 was higher in
      solid metastases compared to effusions (p=0.023), and a trend for higher MGST1
      levels in solid metastases compared to primary tumors was observed (p=0.06).
      Biopsies from primary carcinomas obtained from patients with >200 ml ascites at
      diagnosis had higher mRNA expression of MGST1 compared to samples from patients
      with <200 ml ascites (p=0.037). MGST1 mRNA expression was not associated with
      age, histological grade, tumor stage, residual disease volume, response to
      chemotherapy, chemotherapy resistance or survival. Western blot analysis of
      patient-matched effusions showed high concordance between MGST1 protein and mRNA
      levels measured by qRT-PCR (p<0.001). CONCLUSIONS: The present study documents
      frequent MGST1 mRNA and protein expression in OC. The data suggest increased
      activity of oxidative response pathways, reflected by higher mRNA expression, in
      solid OC tumors compared to metastatic effusions. Additionally, a tumor
      microenvironment consisting of ascites may induce antioxidant activity.

PMID- 22652155
TI  - Biomechanical modification and sense motor control of body posture after plastic
      surgery.
AB  - Plastic surgery offers a quite unique window on abrupt and permanent
      modifications of a human&#x0027;s body schema. Its impact is comparable to
      amputations or other severe injuries, with the evident advantage from the
      experimenter&#x0027;s (and patient&#x0027;s) point of view that it is planned,
      allowing longitudinal studies and quantification of the weight and distribution
      of modified bodily masses (e.g., weight of the prosthesis). One potential
      drawback is that modifications due to (aesthetic) plastic surgery are often too
      little to be revealed by motor control tasks, making it difficult to measure the
      time course of body schema readaptation. The aim of our study is measuring the
      capability of the body scheme to re-adapt to significant and abrupt changes, such
      as the distribution of mass centers, and in particular to assess what is the time
      course of such re-adaptation. For this reason, we have carried out a longitudinal
      study on postural modifications on a population of female patients (N = 30) who
      were subjected to additive or reductive plastic surgery. Posture and stabilometry
      evaluations were performed before surgery (T0), and after 1 months (T1), 4 months
      (T2), and 1 year (T3). Posture was reconstructed from spatial tracking system
      (FastrackTM Polhemus) recordings. Stabilometry analysis was performed by force
      platform (Globus Italia). The results document a modification in posture and a
      significant increase in the sway area after body mass alterations. Posture and
      stabilometry data return to equilibrium after 1 year. Our data suggest that
      posture control relies on, at least in part, feedforward than only on feedback
      strategies.

PMID- 22652156
TI  - Flexible flatfoot treatment in children with mechanical sound vibration therapy.
AB  - The flat foot can be defined as a syndrome with multiple etiopathogenesis,
      characterized by an altered structure of the longitudinal arch of the plantar
      vault with its reduction in height. The plantar arch collapse can be counteracted
      by strengthening the muscles involved; for many years, specific physical
      exercises have been proposed with this purpose in physical and rehabilitation
      medicine. The aim of our work was to improve the plantar arch muscles' tone using
      high focal vibration therapy (300Hz) METHODS: 10 children with a 4th degree flat
      foot (age: 8,7+/-2,2; height: 132+/-15cm; weight: 35,2+/-12,3Kg) underwent 10
      sessions, 2 days/wk, of 30 min of focused high vibratory therapy at a frequency
      of 300 Hz (Vissman, Italy). Before and after treatment stabilometry (StT), static
      and dynamic baropodometry tests were performed. RESULTS: Evaluation of StT showed
      an improvement of stability, a decrease of sway area and ellipse area.
      Baropodometry tests showed a decrease in foot surface. Also dynamic tests showed
      a decrease in both foot surfaces. DISCUSSION: The results lead us to consider
      this method as a method of first choice to a conservative approach in the
      rehabilitation of flat foot syndrome also for the 4th grade in children.

PMID- 22652157
TI  - Visual sensory disability: rehabilitative treatment in an aquatic environment.
AB  - The outcome of this study is based on the concept of the enormous potentiality
      that is expressed, after the elimination of myofascial and articular
      compensation, from the body system. 10 low vision and blind subjects aged between
      35 and 50 years. The subjects performed 10 sessions (2/week) for 5 weeks. Each
      session consisted of a training in the gym (30 minutes) and hydrokinetic therapy
      (45 minutes) All the subjects at the beginning (T0) and at the end (T1) of the
      rehabilitation program were tested by static baropodometry and the stabilometric
      (Milletrix, Diagnostic support, Rome, Italy). Our results shows an increase of
      the total area of support surface (p0.05). The stabilometry results shows an
      improvement of the orthostatic balance, sway area and the ellipse area decrease
      respectively 15% (236,9vs201 p<=0.05) and 41% b(p<=0.05). Thus, the energy
      expenditure of the patient in maintaining the orthostatic position without visual
      afferences is lower. Rehabilitative treatment in an aquatic environment resulted
      effective in improving posture and balance in all patients with increased
      precision in the execution of the step, which implies less effort during walk,
      less energy consumption and better quality of life.

PMID- 22652158
TI  - Botulinum toxin type A in cervical dystonia.
AB  - Cervical dystonia is a syndrome characterized by anomalous postures and
      unintentional repetitive movements of the head and the neck. Aim of this study is
      to show the effectiveness of the combined treatment botulinum toxin-FKT through
      the use of a recent methodic of investigation, myoton, and of the classical
      clinical evaluations, such as Tsui and VAS scales. 15 patients (9 females, 6
      males) have been selected. During the initial visit and in the following
      controls, performed every month, patients have been submitted to physiatric
      examination, clinical evaluation of the dystonia through the Tsui scale, clinical
      evaluation of the pain through the VAS scale, myometric evaluation. We obtained a
      statistical reduction of muscular tone values in passive elongation
      (t0=16,34&#x00B1;1,23) until 4 month (t4 =16,11&#x00B1;1,23), when we performed a
      second infiltration. After 4 months from the second infiltration
      (t8=15,99&#x00B1;1,11) value did not present more some statistical correlation
      and was necessary to perform a new infiltration. Values of elasticity, stiffness,
      Tsui and VAS scale followed the same course of the tone. Our study demonstrates
      that combined treatment botulinum toxin-FKT is effective. It emerges that if to
      the treatment with botulinum toxin follows a suitable FKT treatment, the effect
      of the drug lasts 4 months and not 3 months as described by the literature. Our
      study has underlined that using myometric measurement we can consider least
      changes in muscular tone, elasticity and stiffness; we have a broader view of the
      spastic muscle, and we can better plan appropriate rehabilitative care for each
      patient.

PMID- 22652159
TI  - Pharmacological aspects and neurological speech therapy: target of dysphony,
      dysarthria and dysphagia.
AB  - The word dysphagy was suggested by Nicolatopoulos (1907) and derives from the
      ancient Greek &#x0022;duz&#x0022;, which means &#x0022;difficulty&#x0022; and
      &#x0022;katapinein&#x0022;, which means &#x0022;to swallow&#x0022;. Generally,
      the dysphagia is defined on the basis of its origin: oral, pharynx and
      oesophagus, otherwise by its mechanical or neurological aetiology. The symptoms
      are dependent on the nature of the lesions in the affected organs. The swallow is
      a complex motor sequence dependent on the coordinate contraction of the muscle of
      mouth, of larynx and of the oesophagus. The mechanical action of the swallow
      helps the liquid or solid food progression from mouth to stomach thanks to
      cooperation of 31 muscles and 5 cranial nerves and allows swallowing about 580
      times approximately. The dysphagy in neurological diseases is mainly due to the
      following reasons. Increase of vascular cerebral disease, increase of population
      age and increase of road and work traumas. The difficulties in swallowing causes
      heavy social problems like meager diet, social isolation and worsening of quality
      of life. The speech rehabilitation requires the involvement of care givers
      through a re-educational program that takes place in two periods: the first of
      relaxation, and the second of restoration of phonodeglutition praxis.

PMID- 22652160
TI  - Combined antimuscarinics for treatment of neurogenic overactive bladder.
AB  - Antimuscarinic drugs are the first line pharmacotherapy for overactive bladder,
      but they are not always effective to achieve complete continence. Nevertheless in
      some patients urodynamic investigations reveal insufficient effects with
      continuing incontinence events even with dose optimization. The aim of this study
      is to evaluate the effect of association of Oxybutynin chloride, Trospium
      chloride and Solifenacin succinate administered orally for a minimum of 12 weeks
      in subjects with suprasacral spinal cord injury with urge-incontinence,
      urodynamic?proven neurogenic detrusor overactivity dysfunction and detrusor
      external sphincter dyssynergia to improve level of continence, reduce the risks
      of urologic complications and enhance QOL. This study was a randomized, double
      blind, controlled, balanced-parallel-groups investigation of orally administed
      Oxybutynin in addition to Trospium chloride in the first group and Oxybutynin in
      addition to Solifenacin in the other group. A total of 12 patients with
      neurogenic detrusor overactivity and clean intermittent catheterization were
      allocated into two treatment groups: 5 mg tablet of Oxibutinin and 20 mg tablet
      of Trospium Chloride were administered respectively 3 times a day and 4 times a
      day in the first group (Group A). 5 mg tablet of Oxibutinin and 10 mg tablet of
      Solifenacin were administered respective 3 times a day and once daily in the
      second group (Group B). In both group of patients we found a significant decrease
      in incontinence episodes, with an improvement of bladder compliance, bladder
      capacity and volume voided. Side effects were higher in patients of group B, but
      in generally well tolerated. In conclusion, a combined antimuscarinic treatment
      might be a right option for patients affected by neurogenic bladder refractory to
      previous antimuscarinic monotherapy, and might slow down or delay other more
      invasive treatments.

PMID- 22652161
TI  - Effects of herbal supplements on the immune system in relation to exercise.
AB  - Athletes who undergo strenuous exercise, especially in endurance sports,
      frequently use herbal supplements in order to have a better performance. In this
      review we try to find out if the most common herbal supplements (Echinacea,
      Rhodiola, Ginseng) are effective in the empowerment of performance or in the
      modulation of the immune system. It seems that the prevalent effect is
      adaptogenic rather than ergogenic, with a better tolerance of the exercise
      induced stress, related to enhancement of the whole immune system and decrease of
      the oxidative damage.

PMID- 22652162
TI  - Associated with intrathecal baclofen treatment and duloxetine in patients with
      multiple sclerosis.
AB  - Baclofen is now used in treatment of patients with severe spasticity secondary to
      neurological diseases through the direct infusion of the drug into the
      subarachnoid space with an implanted programmable pump. Among patients whose
      quality of life improved after the use of intrathecal systems, a very important
      role belongs to people with multiple sclerosis (MS): a disease that due to a
      great variety of symptoms and signs, seriously affects the activities of daily
      living. Among the clinical manifestations of MS are also found mental health
      problems including depression mood. The drugs most commonly offered, for
      treatment of depression in patients with MS, are selective serotonin reuptake
      inhibitors (SSRIs), reuptake inhibitors of serotonin and norepinephrine (SNRIs)
      and tricyclic antidepressants (TCA). Duloxetine presents a high affinity for
      transporters reuptake of serotonin and noradrenalin, and exerts its activity on
      both molecules. In addiction, Duloxetine has demonstrated very effective in
      treatment of depressive disorders of mood as demonstrated by scientific evidences
      about the utility of Duloxetine in the modulation of painful physical symptoms
      associated with depression and in treatment of pain associated with diabetic
      neuropathy. The purpose of our study is to evaluate the effects of antidepressant
      therapy with duloxetine, 60 mg/day in 7 patients with multiple sclerosis treated
      with intrathecal baclofen for spastic modulation of tone. The experience we
      gained, according to data from several multicenter trials confirmed the efficacy
      of Baclofen intrathecally administered, especially with regards to modulation of
      spasticity. Our study also showed, although the limitations of a small sample
      size still, a good clinical response to combined treatment Baclofen
      intrathecal/duloxetine 60 mg/day.

PMID- 22652163
TI  - Treatment of upper limb spasticity after stroke: one-year safety and efficacy of
      botulinum toxin type A NT201.
AB  - A new preparation of botulinum toxin type A called NT 201, free from complexing
      proteins, potentially with low antigenicity has been used in the therapy of
      spasticity in stroke patients. This was an open-label study reported the safety
      and the efficacy of one-year treatment with NT 201 evaluating the therapeutic
      effect on functional disability and on quality of life in upper limb spasticity
      after stroke. Patients received a botulinum toxin therapy in the upper injected
      intramuscularly. After inoculation, patients were submitted to a motor
      rehabilitation program for upper limb injected three times/week. Re-treatment was
      permitted at 12 weeks after the prior treatment. Safety assessment included
      evaluation of adverse events and efficacy was measured by Modified Ashworth Scale
      for spasticity (MAS), Spasm Frequency Score (SFS) for the daily spasms, and
      Disability Assessment Scale (DAS) for disability. Of 35 consecutive patients (13
      women and 12 men) screened for study eligibility, 20 (6 women and 14 men)
      patients (mean age 63,4+/-7,03) were included in this study and were submitted to
      NT 201 therapy for one year. At the baseline, botulinum toxin dose in the upper
      limb ranged from 160 to 450U, whereas total dose in the last treatment
      administrated was reduced respect the first injections ranging from 120 to 350U.
      All the enrolled patients completed the year-long study and reported an
      improvement of clinical picture. MAS, was statistically (px003C;0,001) reduced in
      all muscles at T1 (mean score +/-SD: 2.65+/-0.67) and T2 (mean score+/-SD: 2.55+/
      0.60) in comparison to the baseline T0 (mean score+/-SD: 3.9 +/-0.78).
      Significant reduction (px003C;0,001) from baseline T0 (mean score +/-SD: 3.25+/
      0.78) was also noted in SFS at T1 (mean score +/-SD: 1.55+/-0.51) and T2 (mean
      score+/-SD :1.30+/-0.47). The DAS score showed a reduction of the T1score (mean
      score +/-SD: 1.70+/-0.47) and T2 score (mean score +/-SD: 1,40 +/-0,50) respect
      to baseline T0 score (mean score +/-SD: 2,65 +/-0,48) statistically significant
      (p<=003C;0,001). No adverse effects were observed in these patients. NT 201
      appeared to be an efficacious and well-tolerated long-term treatment option for
      patients with upper limb spasticity after stroke, obtaining a substantial
      improvement in functional disability, muscle hypertone, and daily spasms.

PMID- 22652164
TI  - Listeriolysin O: the Swiss army knife of Listeria.
AB  - Listeriolysin O (LLO) is a toxin produced by Listeria monocytogenes, an
      opportunistic bacterial pathogen responsible for the disease listeriosis. This
      disease starts with the ingestion of contaminated foods and mainly affects
      immunocompromised individuals, newborns, and pregnant women. In the laboratory,
      L. monocytogenes is used as a model organism to study processes such as cell
      invasion, intracellular survival, and cell-to-cell spreading, as this Gram
      positive bacterium has evolved elaborate molecular strategies to subvert host
      cell functions. LLO is a major virulence factor originally shown to be crucial
      for bacterial escape from the internalization vacuole after entry into cells.
      However, recent studies are revisiting the role of LLO during infection and are
      revealing new insights into the action of LLO, in particular before bacterial
      entry. These latest findings along with their impact on the infectious process
      will be discussed.

PMID- 22652165
TI  - Staphylococcus aureus endocarditis with fast development of aortic root abscess
      despite relevant antibiotics.
AB  - We present a case of Staphylococcus aureus endocarditis in which a large abscess
      was formed in only 4 days, despite specific intravenous antibiotics and only few
      vague signs of disease progression. Our case seems to be the first to show
      echocardiographic documentation of how quickly an intracardiac abscess can
      develop despite relevant antibiotics. Clinically, the patient is remarkably
      unaffected, and thus even small signs of progression should lead to
      considerations about repeating the diagnostic imaging workup. This case
      illustrates how aggressive an infection S. aureus endocarditis may be, and
      therefore it should be treated by an experienced team with easy access to both
      transthoracic and transesophageal echocardiography.

PMID- 22652166
TI  - The experience of fatigue as a distressing symptom of heart failure.
AB  - OBJECTIVE: We explored the perceptions, experience, and meaning of fatigue as a
      distressing symptom of chronic heart failure (HF). BACKGROUND: Fatigue, a common
      symptom of HF, may indicate worsening condition. Patients interpret their
      symptoms to determine the need for assistance. The meaning of fatigue in everyday
      life for HF patients in the United States is not well understood. METHODS: We
      performed an interpretive study of in-depth interviews with HF patients (n = 26)
      who reported fatigue as a symptom, using a thematic analysis of transcripts
      within an iterative group framework. RESULTS: Fatigue is characterized by patient
      values related to their self-identity, their body, their experience of time,
      their environment, and their relationships with others, including the healthcare
      system. CONCLUSIONS: Fatigue influences perceived proximity to death and how
      patients try to preserve what they can do. A patient's HF management plan should
      be tailored and responsive to that patient's experience of fatigue as
      communicated by the patient.

PMID- 22652167
TI  - Depressive symptoms and healthcare utilization in patients with noncardiac chest
      pain compared to patients with ischemic heart disease.
AB  - OBJECTIVES: We compared depressive symptoms and healthcare utilization in
      patients admitted for noncardiac chest pain, acute myocardial infarction, and
      angina pectoris after hospitalization and at 1-year follow-up. METHODS: One
      hundred and thirty-one patients with noncardiac chest pain, 66 with acute
      myocardial infarction, and 70 with angina pectoris completed a depression
      screening questionnaire and the Montgomery Asberg Depression Rating Scale.
      Healthcare utilization data were collected from a population-based, diagnosis
      related database. RESULTS: More than 25% of respondents reported depressive
      symptoms, regardless of diagnosis. At follow-up, 9% had recovered, 19% were still
      experiencing depressive symptoms, and 13% had developed depressive symptoms.
      Noncardiac patients with chest pain had similar primary care contacts, but fewer
      hospital admissions, than patients with an acute myocardial infarction. Patients
      with angina pectoris and depressive symptoms used the most healthcare services.
      CONCLUSIONS: Depressive symptoms were common. Patients with noncardiac chest pain
      used as much primary care as did patients with an acute myocardial infarction.
      Interventions should focus on identifying and treating depressive symptoms.

PMID- 22652168
TI  - Octreotide-induced asystolic events in an intensive care unit patient with
      gastrointestinal bleeding.
AB  - Octreotide is a somatostatin analogue used to control upper gastrointestinal
      bleeding. We report a case of a patient with no significant cardiac history who
      had multiple asystolic events during an octreotide infusion at a relatively low
      dose. Although octreotide leading to bradycardia and heart block has been
      documented in several case reports, to our knowledge, octreotide-associated
      asystole has not been described. It is pertinent that physicians must be aware of
      this significant cardiac effect for vigilant cardiac monitoring and management,
      preferably in an intensive care setting. Furthermore, this suggests that although
      dose- and route-related effects have been described, some individuals may be
      susceptible at low doses, even in the absence of heart disease. There were no
      further recurrences after the drug was discontinued.

PMID- 22652169
TI  - Esophageal achalasia compressing left atrium diagnosed by echocardiography using
      a liquid containing carbon dioxide in a 21-year-old woman with Turner syndrome.
AB  - Extrinsic compression of the left atrium by the esophagus, the stomach, or both
      is an uncommon but important cause of hemodynamic compromise. Achalasia is a
      motility disorder characterized by impaired relaxation of the lower esophageal
      sphincter and dilatation of the distal two thirds of the esophagus.
      Echocardiographic imaging after oral ingestion of liquid containing carbon
      dioxide allowed for differentiation between a compressive vascular structure and
      the esophagus. We report a rare case of esophageal achalasia compressing the left
      atrium diagnosed by echocardiography using a liquid containing carbon dioxide in
      a 21-year-old woman with Turner syndrome.

PMID- 22652170
TI  - Pacemaker endocarditis caused by Propionibacterium acnes: a case report.
AB  - A 74-year-old man, with a permanent pacemaker placed 2 years ago for high-grade
      atrioventricular block, was admitted for worsening fatigue, confusion, and
      thrombocytopenic purpura without fever. White blood cell count and C-reactive
      protein were elevated, and echocardiography revealed a 6 * 3-cm echogenic mass
      surrounding the pacemaker leads. Multiple blood cultures were performed, and only
      1 bottle grew Propionibacterium acnes at 93 hours. The patient underwent surgery,
      and 16S rRNA gene polymerase chain reaction amplification confirmed the presence
      of P. acnes in the removed vegetation. Patients with late-onset, device-related
      endocarditis often present with vague symptoms and fever may be absent, obscuring
      the clinical diagnosis. Blood cultures and transesophageal echocardiography are
      key diagnostic tests. As a slow-growing, low virulent, and common human skin
      germ, P. acnes can be wrongly considered as a blood culture contaminant.

PMID- 22652171
TI  - Ventricular tachycardia: how many beats?

PMID- 22652172
TI  - The predictive value of plasma cystatin C for acute coronary syndrome treated
      with percutaneous coronary intervention.
AB  - BACKGROUND: This study was designed to evaluate the value of plasma cystatin C in
      predicting adverse cardiac events after percutaneous coronary intervention (PCI)
      for acute coronary syndrome (ACS). METHODS: A total of 605 patients (404 male,
      mean age 60.4 +/- 10.6 years) with ACS underwent successful PCI. Patients were
      divided into 4 groups according to the level of cystatin C, which was measured
      before the PCI: Q1 (<1.02 mg/L), Q2 (1.02-1.16 mg/L), Q3 (1.17-1.34 mg/L), and Q4
      (>=1.35 mg/L). RESULTS: After a follow-up of 14.3 +/- 1.7 months, the incidence
      of mortality, nonfatal myocardial infarction, and target lesion revascularization
      in the Q2, Q3, and Q4 groups was higher than in the Q1 group (P < .001). The
      incidence of heart failure in the Q3 and Q4 groups was higher than in the Q1
      group (P < .05). Multivariate Cox regression analysis showed that cystatin C
      elevation was an independent predictor of major adverse cardiac events. The
      cumulative survival rate of the Q3 and Q4 groups was lower than in the Q1 group
      (P < .001). CONCLUSION: High plasma cystatin C concentration is an independent
      predictor of major adverse cardiac events in patients with ACS treated with PCI.

PMID- 22652173
TI  - Activation of canonical WNT/beta-catenin signaling enhances in vitro motility of
      glioblastoma cells by activation of ZEB1 and other activators of epithelial-to
      mesenchymal transition.
AB  - Here we show that activation of the canonical WNT/beta-catenin pathway increases
      the expression of stem cell genes and promotes the migratory and invasive
      capacity of glioblastoma. Modulation of WNT signaling alters the expression of
      epithelial-to-mesenchymal transition activators, suggesting a role of this
      process in the regulation of glioma motility. Using immunohistochemistry in
      patient-derived glioblastoma samples we showed higher numbers of cells with
      intranuclear signal for beta-catenin in the infiltrating edge of tumor compared
      to central tumor parenchyma. These findings suggest that canonical WNT/beta
      catenin pathway is a critical regulator of GBM invasion and may represent a
      potential therapeutic target.

PMID- 22652174
TI  - A new protoapigenone analog RY10-4 induces apoptosis and suppresses invasion
      through the PI3K/Akt pathway in human breast cancer.
AB  - RY10-4, a novel protoapigenone analog, shows potent cytotoxicity against a broad
      spectrum of human cancer cells. Here we investigate its anti-tumor activity on
      breast cancer. The results indicated that RY10-4 suppressed proliferation,
      arrested cell cycle, induced apoptosis and inhibited invasion in MDA-MB-231, MCF
      7 and SKBR3 breast cancer cells. Western blot analysis showed that RY10-4 down
      regulated the PI3K/Akt signaling pathway and inhibited doxorubicin-induced p-Akt.
      Moreover, it effectively suppressed tumor growth in mice without major side
      effects. Therefore, RY10-4 had potential anti-tumor activity, and could be used
      as a lead to design more potent derivatives.

PMID- 22652175
TI  - A distinct subpopulation within CD133 positive brain tumor cells shares
      characteristics with endothelial progenitor cells.
AB  - The cell surface marker CD133 has been proposed as a brain tumor stem cell
      marker. However, there have been substantial controversies regarding the
      necessity and role of CD133 in tumorigenesis. This study aimed to characterize
      CD133(+) cells in brain tumors. Human brain tumor specimens and whole blood were
      collected from the same patients (N=12). We carried out dual FACS staining for
      CD133/CD34 and functional tumorigenesis and angiogenesis analyses of CD133(+)
      cells from different origins. We also investigated the in vivo tumorigenic
      potential and histological characteristics of four distinct groups on the basis
      of expression of CD133/CD34 markers (CD133(+), CD133(+)/CD34(+), CD133(+)/CD34(
      ), and CD133(-)). CD133(+) brain tumor cells coexpressed significantly higher
      positivity for CD34 (70.7+/-5.2% in CD133(+) vs. 12.3+/-4.2% in CD133(-) cells,
      P<0.001). CD133(+) brain tumor cells formed neurosphere-like spheroids and
      differentiated into multiple nervous system lineages unlike CD133(+) blood cells.
      They showed biological characteristics of endothelial cells, including vWF
      expression, LDL uptake and tube formation in vitro, unlike CD133(-) brain tumors
      cells. Pathologic analysis of brains implanted with CD133(+) cells showed large,
      markedly hypervascular tumors with well-demarcated boundary. CD133(+)/CD34(-)
      cells produced smaller but highly infiltrative tumors. Notably, pure angiogenic
      cell fractions (CD133(+)/CD34(+)) and CD133(-) tumor cells did not generate
      tumors in vivo. Our data suggest the presence of a distinct subpopulation of
      CD133(+) cells isolated from human brain tumors, with characteristics of
      endothelial progenitor cells (EPCs).

PMID- 22652176
TI  - [Malpractice claims by specialty in a non-US setting].

PMID- 22652177
TI  - The use of skeletal extension torque in reversing Dupuytren contractures of the
      proximal interphalangeal joint.
AB  - Dupuytren contracture of the proximal interphalangeal (PIP) joint can be reversed
      by an extension torque transmitted from an external device, the Digit Widget, by
      skeletal pins to the middle phalanx. This extension torque, generated by the same
      elastic bands dentists use to align teeth, gradually restores length to soft
      tissues palmar to the PIP joint's axis of rotation. Simultaneously, tissues
      dorsal to the joint's axis will shorten toward normal length as the PIP
      progressively straightens. Although the contractile nodules and bands of
      Dupuytren disease may be excised either before or after reversal of the joint's
      contracture, a 2-staged approach is preferred: (1) reverse the PIP flexion
      contracture, and (2) excise the diseased tissue from the straightened finger. We
      believe this 2-staged approach yields better results. In addition, it is
      technically easier to avoid injury to nerves and arteries while excising the
      nodules and bands, when one operates through palmar skin of more nearly normal
      length.

PMID- 22652178
TI  - Titanium integration with bone, welding, and screw head destruction complicating
      hardware removal of the distal radius: report of 2 cases.
AB  - Increasingly, surgeons treat distal radius fractures with locking plate systems.
      Recent case reports have focused on technical insertion errors resulting in
      removal difficulties: poor drilling orientation or cross-threading, destruction
      of the screw head, and filling of the screw recess with tissue. We report 2
      complications of titanium locked plate removal secondary to in vivo reactions
      including titanium integration with bone and mechanical binding between the
      titanium screw and plate. We clarify and discuss terminology relevant to implant
      removal, including cold-welding, galling, fretting, and anodization. Even with
      optimal technique, in situ reactions can complicate titanium implant removal.

PMID- 22652180
TI  - Innovation and innovators: does it take 10,000 hours?

PMID- 22652179
TI  - Salvage of failed resection arthroplasties of the distal radioulnar joint using
      an ulnar head prosthesis: long-term results.
AB  - PURPOSE: The aim of this prospective multicenter study was to evaluate the long
      term outcome of the Herbert ulnar head prosthesis for painful instability of the
      distal radioulnar joint (DRUJ) following resection of the ulnar head. METHODS:
      Twenty-three patients were treated with a Herbert ulnar head prosthesis in 3
      international hand centers. One patient was excluded from the study because a
      septic prosthesis had to be removed after 3 months. Sixteen of the remaining 22
      patients could be assessed at 2 follow-up times, 28 months (range, 10-43 mo) and
      11 years and 2 months (range, 97-158 mo) after surgery, for DRUJ stability,
      forearm rotation, grip strength, pain level (0-10), and satisfaction (0-10).
      Standardized radiographs of the wrist were evaluated for displacement of the
      ulnar head and loosening or bony reactions at the sigmoid notch or the ulna
      shaft. RESULTS: All patients demonstrated a clinically stable DRUJ at the latest
      examination, and no patient required further surgery at the DRUJ since the short
      term evaluation in 1999. Average pain measured 3.7 before surgery, 1.7 at the
      short-term follow-up, and 1.7 at the long-term follow-up; patients' satisfaction,
      2.2, 8.2, and 8.9; pronation, 73 degrees , 86 degrees , and 83 degrees ;
      supination, 52 degrees , 77 degrees , and 81 degrees ; and grip strength, 42%,
      72%, and 81% of the unaffected side. All clinical parameters improved
      significantly from before surgery to the short-term follow-up, with no further
      statistically significant change between the short-term and long-term follow-up.
      Radiographs demonstrated no signs of stem loosening or incongruity of the DRUJ.
      CONCLUSIONS: The previously reported short-term results with the Herbert
      prosthesis did not deteriorate in the long term. Reconstruction of the DRUJ with
      this prosthesis in painful radioulnar impingement following ulnar head resection
      is a reliable and reproducible procedure with lasting results.

PMID- 22652181
TI  - Perioperative management of rheumatoid medications.

PMID- 22652182
TI  - The importance of shoulder external rotation in activities of daily living:
      improving outcomes in traumatic brachial plexus palsy.
AB  - PURPOSE: To define the importance of shoulder external rotation in activities of
      daily living in normal individuals to better understand how restoration of
      shoulder external rotation in traumatic brachial plexus palsy could improve
      patient function. METHODS: Thirty-one normal individuals performed 12 common
      activities of daily living (ADLs) wearing a custom shoulder orthosis designed to
      selectively limit shoulder external rotation to 3 different settings, ranging
      from 0 degrees  (most restrictive) to 90 degrees  (least restrictive) of external
      rotation. Outcomes were measured with a visual analog scale of perceived
      difficulty in accomplishing the ADLs with each orthosis setting and the
      Disabilities of the Arm, Shoulder, and Hand questionnaire administered after each
      set of 12 ADLs was completed. RESULTS: Subjects perceived increasing difficulty
      during all ADLs tested and registered higher disability scores with increasing
      restriction of shoulder external rotation. The ADLs requiring motions
      predominantly above the waist exhibited more marked and earlier changes in visual
      analog scale scores with increasing shoulder external rotation restriction.
      CONCLUSIONS: Traditionally, surgeons have pursued restoration of shoulder
      abduction and forward elevation in secondary reconstruction of traumatic brachial
      plexus injuries. Recently, the concept of preferentially restoring shoulder
      external rotation has been proposed, without clear evidence in the literature of
      the role of shoulder external rotation in ADLs. CLINICAL RELEVANCE: Our results
      support the notion that restoring shoulder external rotation in the treatment of
      traumatic brachial plexus palsy patients might improve outcomes by decreasing
      patient disability and increasing the ability to perform ADLs.

PMID- 22652183
TI  - Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent
      salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin
      lymphoma: a phase 3, multicentre, open-label, randomised trial.
AB  - BACKGROUND: Pixantrone dimaleate (pixantrone)--a novel aza-anthracenedione--was
      synthesised to reduce anthracycline-related cardiotoxicity without compromising
      antitumour efficacy. We aimed to assess the efficacy and safety of pixantrone
      versus an investigator's choice of a single-agent therapy in heavily pretreated
      patients with relapsed or refractory aggressive non-Hodgkin lymphoma. METHODS: In
      this phase 3, multicentre, open-label, randomised trial at 66 hospitals in
      Europe, India, Russia, South America, the UK, and the USA, patients with
      histologically confirmed aggressive non-Hodgkin lymphoma who had relapsed after
      two or more previous chemotherapy regimens were randomly assigned (1:1) by an
      interactive voice response system to treatment with pixantrone dimaleate (85
      mg/m(2) intravenously on days 1, 8, and 15 of a 28-day cycle, for up to six
      cycles) or to a comparator (vinorelbine, oxaliplatin, ifosfamide, etoposide,
      mitoxantrone, or gemcitabine) given at prespecified standard doses and schedules.
      Patients were stratified by region, International Prognostic Index score, and
      previous stem-cell transplantation. Patients and investigators were not masked to
      treatment assignment; however, an independent assessment panel was masked. The
      primary endpoint was the proportion of patients with a complete or unconfirmed
      complete response in the intention-to-treat (ITT) population at the end of
      treatment. Primary analyses of efficacy were based on the independent assessment
      panel's data review. The study is registered at ClinicalTrials.gov, number
      NCT00088530. FINDINGS: The ITT population comprised 70 patients randomly assigned
      to the pixantrone group and 70 to the comparator. Five patients (two in the
      pixantrone group and three in the comparator group) dropped out before receiving
      their study drug. 14 patients (20.0% [95% CI 11.4-31.3]) who received pixantrone
      achieved a complete or unconfirmed complete response at end of treatment compared
      with four patients (5.7% [1.6-14.0]) in the comparator group (p = 0.021). The
      most common grade 3 or 4 adverse events in patients given pixantrone were
      uncomplicated, non-cumulative neutropenia (28 [41.2%] of 68 patients vs 13
      [19.4%] of 67 patients in the comparator group), leucopenia (16 [23.5%] vs five
      [7.5%]), and thrombocytopenia (eight [11.8%] vs seven [10.4%]). INTERPRETATION:
      Pixantrone, given as a single-agent salvage therapy in heavily pretreated
      patients with relapsed or refractory aggressive non-Hodgkin lymphoma, is
      efficacious and tolerable. It could be a treatment option for patients whose
      aggressive non-Hodgkin lymphoma has failed to respond to at least two previous
      chemotherapy regimens. FUNDING: Cell Therapeutics, Inc.

PMID- 22652184
TI  - Pixantrone: a new agent for relapsed aggressive lymphomas.

PMID- 22652186
TI  - [Efficacy and safety of botulinum toxin in the treatment of sialorrhea in
      children with neurological disorders].

PMID- 22652185
TI  - The role of saposin C in Gaucher disease.
AB  - Saposin C is one of four homologous proteins derived from sequential cleavage of
      the saposin precursor protein, prosaposin. It is an essential activator for
      glucocerebrosidase, the enzyme deficient in Gaucher disease. Gaucher disease is a
      rare autosomal recessive lysosomal storage disorder caused by mutations in the
      GBA gene that exhibits vast phenotypic heterogeneity, despite its designation as
      a "simple" Mendelian disorder. The observed phenotypic variability has led to a
      search for disease modifiers that can alter the Gaucher phenotype. The PSAP gene
      encoding saposin C is a prime candidate modifier for Gaucher disease. In humans,
      saposin C deficiency due to mutations in PSAP results in a Gaucher-like
      phenotype, despite normal in vitro glucocerebrosidase activity. Saposin C
      deficiency has also been shown to modify phenotype in one mouse model of Gaucher
      disease. The role of saposin C as an activator required for normal
      glucocerebrosidase function, and the consequences of saposin C deficiency are
      described, and are being explored as potential modifying factors in patients with
      Gaucher disease.

PMID- 22652187
TI  - De novo lipogenesis in the liver and adipose tissues of ducks during early growth
      stages after hatching.
AB  - In vivo de novo lipogenesis (DNL) in the liver and adipose tissues of ducks
      during early developmental stages after hatching has not previously been
      investigated. In this study, female Peking ducks (Anas platyrhynchos) at weeks 1
      to 8 post-hatching were selected for experimentation. We measured the mRNA levels
      of 6 DNL-related genes in the duck liver, subcutaneous adipose tissue and
      abdominal adipose tissue by real-time PCR during the 8 weeks. Correlations of the
      plasma triacylglycerol (TG) and very low density lipoprotein (VLDL)
      concentrations with fat deposition at these sites were also detected during
      growth. Our results showed that fat content was highest in the subcutaneous
      adipose tissue and lowest in the liver during the growth period we studied.
      Additionally, plasma VLDL and TG were significantly associated with lipid content
      in adipose tissue (P<0.05), but not in the liver. Lastly, in the growing birds,
      the expression levels of lipogenic genes (with the exceptions SREBP-1c and SCD1)
      were much higher in the liver than in the adipose tissues, and the maximal
      expression levels of these genes occurred at week 4 or 5 at these sites. These
      findings indicated that the main site of DNL is always the liver in post-hatching
      ducks, and adipose tissues are of little importance for DNL. Taken together, our
      results suggested that the plasma lipoproteins contribute greatly to fat
      deposition in adipose tissues originating from hepatic lipogenesis.

PMID- 22652189
TI  - Robust scale-space filter using second-order partial differential equations.
AB  - This paper describes a robust scale-space filter that adaptively changes the
      amount of flux according to the local topology of the neighborhood. In a manner
      similar to modeling heat or temperature flow in physics, the robust scale-space
      filter is derived by coupling Fick's law with a generalized continuity equation
      in which the source or sink is modeled via a specific heat capacity. The filter
      plays an essential part in two aspects. First, an evolution step size is
      adaptively scaled according to the local structure, enabling the proposed filter
      to be numerically stable. Second, the influence of outliers is reduced by
      adaptively compensating for the incoming flux. We show that classical diffusion
      methods represent special cases of the proposed filter. By analyzing the
      stability condition of the proposed filter, we also verify that its evolution
      step size in an explicit scheme is larger than that of the diffusion methods. The
      proposed filter also satisfies the maximum principle in the same manner as the
      diffusion. Our experimental results show that the proposed filter is less
      sensitive to the evolution step size, as well as more robust to various outliers,
      such as Gaussian noise, impulsive noise, or a combination of the two.

PMID- 22652188
TI  - Controversies in family planning: postabortal pelvic inflammatory disease.

PMID- 22652190
TI  - Frame fundamental high-resolution image fusion from inhomogeneous measurements.
AB  - Frame and fusion frame high-resolution image fusion formulations are presented.
      These techniques use the physical point spread function (PSF) of cameras as the
      building block of the mathematical frames in the fusion process. Cameras
      producing the low-resolution images are allowed to be different, and thereby
      possess different PSFs. Fused image reconstructions are carried out by a
      dimension invariance principle and by a set of iterative reconstruction
      algorithms. These frame fundamental approaches are also seen to be robust to
      realistic fusion problems from inhomogeneous image measurements (taken at
      different space or time or by different cameras), which is one of the main
      focuses of this paper. The effectiveness of this approach is demonstrated through
      both simulated and realistic examples. The results are quite encouraging.

PMID- 22652191
TI  - Multiview image coding using depth layers and an optimized bit allocation.
AB  - In this paper, we present a novel wavelet-based compression algorithm for
      multiview images. This method uses a layer-based representation, where the 3-D
      scene is approximated by a set of depth planes with their associated constant
      disparities. The layers are extracted from a collection of images captured at
      multiple viewpoints and transformed using the 3-D discrete wavelet transform
      (DWT). The DWT consists of the 1-D disparity compensated DWT across the
      viewpoints and the 2-D shape-adaptive DWT across the spatial dimensions. Finally,
      the wavelet coefficients are quantized and entropy coded along with the layer
      contours. To improve the rate-distortion performance of the entire coding method,
      we develop a bit allocation strategy for the distribution of the available bit
      budget between encoding the layer contours and the wavelet coefficients. The
      achieved performance of our proposed scheme outperforms the state-of-the-art
      codecs for several data sets of varying complexity.

PMID- 22652192
TI  - Single-image super-resolution reconstruction via learned geometric dictionaries
      and clustered sparse coding.
AB  - Recently, single image super-resolution reconstruction (SISR) via sparse coding
      has attracted increasing interest. In this paper, we proposed a multiple
      geometric-dictionaries-based clustered sparse coding scheme for SISR. Firstly, a
      large number of high-resolution (HR) image patches are randomly extracted from a
      set of example training images and clustered into several groups of "geometric
      patches," from which the corresponding "geometric dictionaries" are learned to
      further sparsely code each local patch in a low-resolution image. A clustering
      aggregation is performed on the HR patches recovered by different dictionaries,
      followed by a subsequent patch aggregation to estimate the HR image. Considering
      that there are often many repetitive image structures in an image, we add a self
      similarity constraint on the recovered image in patch aggregation to reveal new
      features and details. Finally, the HR residual image is estimated by the proposed
      recovery method and compensated to better preserve the subtle details of the
      images. Some experiments test the proposed method on natural images, and the
      results show that the proposed method outperforms its counterparts in both visual
      fidelity and numerical measures.

PMID- 22652193
TI  - Super resolution image reconstruction through Bregman iteration using morphologic
      regularization.
AB  - Multiscale morphological operators are studied extensively in the literature for
      image processing and feature extraction purposes. In this paper, we model a
      nonlinear regularization method based on multiscale morphology for edge
      preserving super resolution (SR) image reconstruction. We formulate SR image
      reconstruction as a deblurring problem and then solve the inverse problem using
      Bregman iterations. The proposed algorithm can suppress inherent noise generated
      during low-resolution image formation as well as during SR image estimation
      efficiently. Experimental results show the effectiveness of the proposed
      regularization and reconstruction method for SR image.

PMID- 22652194
TI  - Does Oenococcus oeni produce histamine?
AB  - The presence of histamine in wine and other fermented foods may pose a
      toxicological risk for consumers. Production of histamine by Oenococcus oeni,
      which is the main agent of malolactic fermentation in wine and thus very
      important for the wine industry, has been extensively analyzed with contradictory
      results. If histamine production by O. oeni strains is a widespread trait,
      enological practices will be affected and the use of non-producing commercial O.
      oeni starters should be strongly recommended to avoid histamine production during
      winemaking. However, a review of published data showed that most evidence
      strongly supports the view that O. oeni is not responsible for histamine
      production in wine. We therefore propose the adoption of common analytical
      methods and the introduction of publicly-available validated histamine-producing
      O. oeni reference strains as a common positive control in assays to resolve this
      important issue.

PMID- 22652195
TI  - Spatial distribution of fallout 137Cs in the coastal marine environment of India.
AB  - The data on the fallout (137)Cs in the coastal marine environment assume
      significance in view of massive expansion of nuclear power plants in the Asia
      Pacific region and to fulfill the benchmark study required to evaluate the
      possible impact of the Fukushima radioactive releases in the Asia-Pacific region.
      Measurements of (137)Cs in sea water, along with salinity and temperature, were
      carried out at 30 locations covering the coastal area of the Arabian Sea and the
      Bay of Bengal. For the present study the Indian coastal area is divided in three
      different regions. The (137)Cs concentration in sea water of the entire Indian
      coastal region varies from 0.30 to 1.25 Bq m(-3). The data obtained in the
      present study was compared with the North Indian Ocean data and it was observed
      that there is a 33% decrease in the Arabian Sea (region I), 50% in the high
      rainfall coastal area (region II) and 24% in the Bay of Bengal (region III).

PMID- 22652196
TI  - Cooperation between classical and alternative NF-kappaB pathways regulates
      proinflammatory responses in epithelial cells.
AB  - The transcription factor NF-kappaB has been causally linked to inflammatory lung
      diseases. Recent studies have unraveled the complexity of NF-kappaB activation by
      identifying two parallel activation pathways: the classical NF-kappaB pathway,
      which is controlled by IkappaB kinase complex-beta (IKKbeta) and RelA/p50, and
      the alternative pathway, which is controlled by IKKalpha and RelB/p52. The
      alternative pathway regulates adaptive immune responses and lymphoid development,
      yet its role in the regulation of innate immune responses remains largely
      unknown. In this study, we determined the relevance of the alternative NF-kappaB
      pathway in proinflammatory responses in lung epithelial cells. The exposure of
      C10 murine alveolar lung epithelial cells to diverse stimuli, or primary murine
      tracheal epithelial cells to LPS, resulted in the activation of both NF-kappaB
      pathways, based on the nuclear translocation of RelA, p50, RelB, and p52.
      Increases in the nuclear content of RelA occurred rapidly, but transiently,
      whereas increases in nuclear RelB content were protracted. The small interfering
      (si) RNA-mediated knockdown of IKKalpha, RelA, or RelB resulted in decreases of
      multiple LPS-induced proinflammatory cytokines. Surprisingly, the siRNA ablation
      of IKKalpha or RelB led to marked increases in the production of IL-6 in response
      to LPS. The simultaneous expression of constitutively active (CA)-IKKalpha and CA
      IKKbeta caused synergistic increases in proinflammatory mediators. Lastly, the
      disruption of the IKK signalsome inhibited the activation of both NF-kappaB
      pathways. These results demonstrate that the coordinated activation of both NF
      kappaB pathways regulates the magnitude and nature of proinflammatory responses
      in lung epithelial cells.

PMID- 22652198
TI  - Trefoil factor-2 reverses airway remodeling changes in allergic airways disease.
AB  - Trefoil factor 2 (TFF2) is a small peptide with an important role in mucosal
      repair. TFF2 is up-regulated in asthma, suggesting a role in asthma pathogenesis.
      Given its known biological role in promoting epithelial repair, TFF2 might be
      expected to exert a protective function in limiting the progression of airway
      remodeling in asthma. The contribution of TFF2 to airway remodeling in asthma was
      investigated by examining the expression of TFF2 in the airway and lung, and
      evaluating the effects of recombinant TFF2 treatment on established airway
      remodeling in a murine model of chronic allergic airways disease (AAD). BALB/c
      mice were sensitized and challenged with ovalbumin (OVA) or saline for 9 weeks,
      whereas mice with established OVA-induced AAD were treated with TFF2 or vehicle
      control (intranasally for 14 d). Effects on airway remodeling, airway
      inflammation, and airway hyperresponsiveness were then assessed, whereas TFF2
      expression was determined by immunohistochemistry. TFF2 expression was
      significantly increased in the airways of mice with AAD, compared with expression
      levels in control mice. TFF2 treatment resulted in reduced epithelial thickening,
      subepithelial collagen deposition, goblet-cell metaplasia, bronchial epithelium
      apoptosis, and airway hyperresponsiveness (all P < 0.05, versus vehicle control),
      but TFF2 treatment did not influence airway inflammation. The increased
      expression of endogenous TFF2 in response to chronic allergic inflammation is
      insufficient to prevent the progression of airway inflammation and remodeling in
      a murine model of chronic AAD. However, exogenous TFF2 treatment is effective in
      reversing aspects of established airway remodeling. TFF2 has potential as a novel
      treatment for airway remodeling in asthma.

PMID- 22652197
TI  - Human epidermal growth factor receptor signaling in acute lung injury.
AB  - Acute lung injury (ALI) is a syndrome marked by increased permeability across the
      pulmonary epithelium resulting in pulmonary edema. Recent evidence suggests that
      members of the human epidermal growth factor receptor (HER) family are activated
      in alveolar epithelial cells during ALI and regulate alveolar epithelial barrier
      function. These tyrosine kinase receptors, which also participate in the
      pathophysiology of pulmonary epithelial malignancies, regulate cell growth,
      differentiation, and migration as well as cell-cell adhesion, all processes that
      influence epithelial injury and repair. In this review we outline mechanisms of
      epithelial injury and repair in ALI, activation patterns of this receptor family
      in pulmonary epithelial cells as a consequence injury, how receptor activation
      alters alveolar permeability, and the possible intracellular signaling pathways
      involved. Finally, we propose a theoretical model for how HER-mediated modulation
      of alveolar permeability might affect lung injury and repair. Understanding how
      these receptors signal has direct therapeutic implications in lung injury and
      other diseases characterized by altered epithelial barrier function.

PMID- 22652200
TI  - High glucose enhances responsiveness of human airways smooth muscle via the
      Rho/ROCK pathway.
AB  - Glucose moves into airway secretions after a glucose load. Therefore people with
      diabetes or hyperglycemia spend a significant proportion of each day with glucose
      in their airways secretions. This study investigated the effects of glucose on
      isolated human airways and on cultured airway smooth muscle (ASM) cells. Human
      isolated bronchi were stimulated with acetylcholine, histamine, and transmural
      stimulation and treated with the selective ROCK inhibitors Y27632 and SB772077B
      under high-glucose conditions. The effect of high glucose concentrations on
      intracellular calcium flux and the phosphorylation of MYPT1 in ASM cells was also
      investigated. High (44 mM for 6 h) glucose, but not mannitol, concentrations led
      to an enhanced responsiveness of ASM to contractile agents. Y27632 and SB772077B
      completely abolished (P < 0.05) the enhanced contractile effects with a high
      concentration glucose solution, compared with control tissues. In cultured ASM
      cells, incubation with high glucose concentrations significantly (P < 0.05)
      enhanced bradykinin-induced intracellular calcium flux and the levels of pMYPT1,
      which were inhibited by Y27632 (P < 0.05). Our study has demonstrated that high
      glucose concentrations leads to hyperresponsiveness of human isolated bronchi and
      enhances intracellular calcium release in cultured ASM cells via a Rho/ROCK- and
      pMYPT1-dependent pathway, suggesting that this crucial pathway may contribute to
      the reduced lung function observed in patients with diabetes. These data propose
      novel targets for the treatment of patients with respiratory diseases that also
      suffer from diabetes mellitus.

PMID- 22652199
TI  - Dynamic regulation of platelet-derived growth factor receptor alpha expression in
      alveolar fibroblasts during realveolarization.
AB  - Although the importance of platelet-derived growth factor receptor (PDGFR)-alpha
      signaling during normal alveogenesis is known, it is unclear whether this
      signaling pathway can regulate realveolarization in the adult lung. During
      alveolar development, PDGFR-alpha-expressing cells induce alpha smooth muscle
      actin (alpha-SMA) and differentiate to interstitial myofibroblasts. Fibroblast
      growth factor (FGF) signaling regulates myofibroblast differentiation during
      alveolarization, whereas peroxisome proliferator-activated receptor (PPAR)-gamma
      activation antagonizes myofibroblast differentiation in lung fibrosis. Using left
      lung pneumonectomy, the roles of FGF and PPAR-gamma signaling in differentiation
      of myofibroblasts from PDGFR-alpha-positive precursors during compensatory lung
      growth were assessed. FGF receptor (FGFR) signaling was inhibited by
      conditionally activating a soluble dominant-negative FGFR2 transgene. PPAR-gamma
      signaling was activated by administration of rosiglitazone. Changes in alpha-SMA
      and PDGFR-alpha protein expression were assessed in PDGFR-alpha-green fluorescent
      protein (GFP) reporter mice using immunohistochemistry, flow cytometry, and real
      time PCR. Immunohistochemistry and flow cytometry demonstrated that the cell
      ratio and expression levels of PDGFR-alpha-GFP changed dynamically during
      alveolar regeneration and that alpha-SMA expression was induced in a subset of
      PDGFR-alpha-GFP cells. Expression of a dominant-negative FGFR2 and administration
      of rosiglitazone inhibited induction of alpha-SMA in PDGFR-alpha-positive
      fibroblasts and formation of new septae. Changes in gene expression of epithelial
      and mesenchymal signaling molecules were assessed after left lobe pneumonectomy,
      and results demonstrated that inhibition of FGFR2 signaling and increase in PPAR
      gamma signaling altered the expression of Shh, FGF, Wnt, and Bmp4, genes that are
      also important for epithelial-mesenchymal crosstalk during early lung
      development. Our data demonstrate for the first time that a comparable epithelial
      mesenchymal crosstalk regulates fibroblast phenotypes during alveolar septation.

PMID- 22652202
TI  - Cross layer design for optimised region of interest of ultrasound video data over
      mobile WiMAX.
AB  - The application of advanced error concealment techniques applied as a post
      process to conceal lost video information in error-prone channels, such as the
      wireless channel, demand additional processing at the receiver. This increases
      the delivery delay and needs more computational power. However, in general, only
      a small region within medical video is of interest to the physician and thus if
      only this area is considered, the number of computations can be curtailed. In
      this paper we present a technique whereby the Region of Interest (ROI) specified
      by the physician is used to delimit the area where the more complex concealment
      techniques are applied. A cross layer design approach in mobile WiMAX wireless
      communication environment is adopted in this paper to provide an optimized
      Quality of Experience (QoE) in the region that matters most to the mobile
      physician while relaxing the requirements in the background, ensuring real-time
      delivery. Results show that a diagnostically acceptable Peak Signal-to-Noise
      Ratio (PSNR) of about 36 dB can still be achieved within reasonable decoding
      time.

PMID- 22652201
TI  - CCAAT/enhancer binding protein-alpha regulates the protease/antiprotease balance
      required for bronchiolar epithelium regeneration.
AB  - Many transcription factors that regulate lung morphogenesis during development
      are reactivated to mediate repairs of the injured adult lung. We hypothesized
      that CCAAT/enhancer binding protein-alpha (C/EBPalpha), a transcription factor
      critical for perinatal lung maturation, regulates genes required for the normal
      repair of the bronchiolar epithelium after injury. Transgenic
      Cebpalpha(Delta/Delta) mice, in which Cebpa was conditionally deleted from Clara
      cells and Type II cells after birth, were used in this study. Airway injury was
      induced in mice by the intraperitoneal administration of naphthalene to ablate
      bronchiolar epithelial cells. Although the deletion of C/EBPalpha did not
      influence lung structure and function under unstressed conditions, C/EBPalpha was
      required for the normal repair of terminal bronchiolar epithelium after
      naphthalene injury. To identify cellular processes that are influenced by
      C/EBPalpha during repair, mRNA microarray was performed on terminal bronchiolar
      epithelial cells isolated by laser-capture microdissection. Normal repair of the
      terminal bronchiolar epithelium was highly associated with the mRNAs regulating
      antiprotease activities, and their induction required C/EBPalpha. The defective
      deposition of fibronectin in Cebpalpha(Delta/Delta) mice was associated with
      increased protease activity and delayed differentiation of FoxJ1-expressing
      ciliated cells. The fibronectin and ciliated cells were restored by the
      intratracheal treatment of Cebpalpha(Delta/Delta) mice with the serine protease
      inhibitor. In conclusion, C/EBPalpha regulates the expression of serine protease
      inhibitors that are required for the normal increase of fibronectin and the
      restoration of ciliated cells after injury. Treatment with serine protease
      inhibitor may aid in the recovery of injured bronchiolar epithelial cells, and
      prevent common chronic lung diseases.

PMID- 22652203
TI  - Minimum 6year results of an uncemented trabecular metal tibial component in total
      knee arthroplasty.
AB  - INTRODUCTION: There are theoretical advantages of using a trabecular metal tibial
      component in total knee replacement (TKR) for long-term survival. We have
      previously reported outcomes at 3 years. We now report the clinical and
      radiological outcome of an unselected series of 109 knees at a minimum of 6 years
      follow up. METHODS: Patient function was assessed in a research clinic using
      Oxford Knee Score (OKS), Clinical and Functional Knee Society Score (KSS) and SF
      12 physical score. Up to date weight bearing radiographs were obtained. RESULTS:
      Seventy-six knees in 72 patients were available for assessment. OKS scores were
      maintained from the 3-year assessment with a mean of 36.1 (8.6). KSS and SF-12
      scores declined slightly but only to a degree previously reported as normal age
      related change. The mean KSS at follow up was 87.2 (17.7). There was no
      radiographic evidence of loosening in any implant. There has been 1 revision for
      unexplained pain at 27 months. CONCLUSION: The uncemented TMT in an unselected
      group is performing as well as any TKR implant at this stage. Future follow up is
      required to ensure this is maintained. The theoretical advantages may make this
      the prosthesis of choice in younger patients. LEVEL OF EVIDENCE: IV. Case series.

PMID- 22652205
TI  - Improving health equity through theory-informed evaluations: a look at housing
      first strategies, cross-sectoral health programs, and prostitution policy.
AB  - The emergent realist perspective on evaluation is instructive in the quest to use
      theory-informed evaluations to reduce health inequities. This perspective
      suggests that in addition to knowing whether a program works, it is imperative to
      know 'what works for whom in what circumstances and in what respects, and how?'
      (Pawson & Tilley, 1997). This addresses the important issue of heterogeneity of
      effect, in other words, that programs have different effects for different
      people, potentially even exacerbating inequities and worsening the situation of
      marginalized groups. But in addition, the realist perspective implies that a
      program may not only have a greater or lesser effect, but even for the same
      effect, it may work by way of a different mechanism, about which we must
      theorize, for different groups. For this reason, theory, and theory-based
      evaluations are critical to health equity. We present here three examples of
      evaluations with a focus on program theories and their links to inequalities. All
      three examples illustrate the importance of theory-based evaluations in reducing
      health inequities. We offer these examples from a wide variety of settings to
      illustrate that the problem of which we write is not an exception to usual
      practice. The 'Housing First' model of supportive housing for people with severe
      mental illness is based on a theory of the role of housing in living with mental
      illness that has a number of elements that directly contradict the theory
      underlying the dominant model. Multisectoral action theories form the basis for
      the second example on Venezuela's revolutionary national Barrio Adentro health
      improvement program. Finally, decriminalization of prostitution and related
      health and safety policies in New Zealand illustrate how evaluations can play an
      important role in both refining the theory and contributing to improved policy
      interventions to address inequalities. The theoretically driven and
      transformative nature of these interventions create special demands for the use
      of theory in evaluations.

PMID- 22652204
TI  - The position of the centre of the femoral head relative to the midline of the
      pelvis: a consistent landmark in total knee replacement surgery.
AB  - BACKGROUND: Femoro-tibial malalignment in excess of 3 degrees  is a recognised
      contributor of early mechanical failure in total knee replacement (TKR).
      Knowledge of the location of the centre of the femoral head is a pre-requisite to
      identification of the mechanical axis of the femur and can facilitate optimal
      component orientation. We investigated variation in the location of the centre of
      the femoral head relative to the midline of the pelvis. METHODS: We analysed the
      pelvic radiographs of 150 patients with unilateral total hip replacements. The
      perpendicular distance from the centre of the femoral head of the non-operated
      hip to the centre of pubic symphysis was measured. RESULTS: The mean distance
      from the centre of the femoral head to the pubic symphysis was 89.2mm (standard
      deviation, 5.7 mm). Patient height strongly correlated with this distance
      (r=0.53, p<0.01), as did the diameter of the femoral head (r=0.59, p<0.01). The
      latter was significantly larger in men than in women (50.9 mm vs. 44.5mm,
      p<0.01). CONCLUSION: The results demonstrate that the position of the centre of
      the femoral head has very little variability, irrespective of patient age or body
      mass index. If the gender-specific mean femoral head to midline distance is used
      to estimate the location of the femoral head centre, a line from this point to
      the centre of the femoral condyles will deviate from the true mechanical axis by
      no more than 1.5 degrees , in 98% of cases.

PMID- 22652206
TI  - The conduct of dental research: the protocol, a guide.
AB  - BACKGROUND: Research today requires detailed planning to ensure efficient work,
      to raise funding and to fit into time constraints. AIM: The aim of this article
      is to provide a broad guidance on the layout and content of a research protocol.
      METHOD: Years of experience in writing research protocols were used to give
      guidance on writing, timings, content, layout and successful completion.

PMID- 22652207
TI  - Risk factors of hypomineralised second primary molars in a group of Iraqi
      schoolchildren.
AB  - AIM: To investigate risk factor/s involved in the development of hypomineralised
      second primary molars and to relate the location of the affected tooth in the
      dental arches with the timing of the illness/condition incidence. STUDY DESIGN: A
      cluster sample of 1,000, Iraqi 7-9 year-old children were invited to have their
      second primary molars examined for demarcated hypomineralised lesions. METHODS:
      Mothers of 823 children completed a questionnaire-based interview regarding
      pregnancy and childhood systemic health history. In the clinical examination, the
      buccal, occlusal and lingual/palatal surfaces of the second primary molar were
      evaluated for demarcated hypomineralisation lesions by visual examination.
      RESULTS: A response rate of 82.3% was obtained. Of the children examined, 53
      (6.6%) had hypomineralisation defects in at least one second primary molar and
      were considered as the hypomineralised second primary molar-affected group. Of
      the total affected teeth (n=83), maxillary molars were the teeth most frequently
      affected by hypomineralisation throughout all developmental stages (69.9%).
      Demarcated opacities were the most prevalent lesion type (71.0%). Ninety-four
      percent of subjects diagnosed with demarcated defects reported various medical
      conditions possibly associated with hypomineralisation compared with 44% for
      their non-affected counterparts. Peri-natal medical conditions (45.3%) were the
      most frequently reported followed by pre-natal and post-natal conditions (24.5%,
      9.4%; respectively). STATISTICS: Ill health during pregnancy, delivery
      complications, neonatal complications, acute childhood illness, birth weight and
      duration of breast feeding were significant potential risk factors (p<0.05). The
      greater the number of health events reported, the higher was the chance of
      developing the defect. Children who experienced neonatal complications and whose
      mothers reported pregnancy and birth problems were approximately six times more
      likely to have the defect than those whose mothers had delivery complications
      only (80% vs 14.6%) (p<0.001). Also of those children whose mothers did not
      report delivery complications, but were breastfed for less than six months, of
      low birth weight and had history of upper respiratory tract infection, the chance
      of hypomineralised defects was over four times more likely to happen than in
      those who did not suffer any of these problems (25.8% vs 6.7%) (p<0.01). No
      statistically significant association was revealed between the time of the
      illness/condition occurrence and the location of the tooth in the dental arches.
      CONCLUSIONS: Children with hypomineralised second primary molars had experienced
      more medical conditions than their unaffected peers particularly during the peri
      natal period. No single factor was identified as a potential cause, leaving the
      aetiology of the defect unclear.

PMID- 22652208
TI  - Post-operative pain and pain management in children after dental extractions
      under general anaesthesia.
AB  - AIM: To evaluate post-operative pain in children and compare self-ratings of pain
      with those of a parent, and to study analgesic use after dental extractions under
      general anaesthesia (GA). STUDY DESIGN: Prospective observational study. METHODS:
      One hundred children, aged 3-12 years, who had extractions performed under GA
      participated. After treatment, the child and one parent assessed post-operative
      pain on 5 occasions: before discharge, the evening of the treatment day, and the
      following three evenings. The parent rated the child's level of pain on a visual
      analogue scale (VAS), and the child made two ratings, one on a facial analogue
      scale (FAS) and one on a coloured analogue scale (CAS). Analgesics were
      recommended 3-4 times daily, and the parent recorded the intake. RESULTS: Seventy
      eight children only had primary teeth extracted, 8 children had both primary and
      permanent teeth extracted, and 14 children only had permanent teeth extracted.
      The median number of extracted primary teeth was 5 (range 1-12) and of permanent
      teeth 3 (range 1-4). The median pain ratings were highest in the post-operative
      ward, VAS=1.0 (max 9.2), FAS=2 (max 10), and CAS=1.4 (max 10). The second highest
      median values were in the evening following treatment. No significant differences
      were found between pain ratings of the parent and the child or between the two
      ratings of the child. 60% took analgesics on day 1. On day 2, 45% took
      analgesics, of which 29% more than once. STATISTICS: Spearman's rank correlation
      coefficient was used to test concordance between ratings. CONCLUSIONS: Most
      children had mild or no pain, and parent and child pain ratings agreed well. The
      dentist's analgesic recommendations were often poorly followed.

PMID- 22652209
TI  - Oral health status of children with autistic disorder in Chennai.
AB  - AIM: To assess the oral health status of autistic children in Chennai. DESIGN AND
      METHODS: Oral health status was assessed for 483 children with autism, solicited
      from special education schools, autistic child centres and therapy centres.
      Conditions assessed were plaque accumulation, gingival health, dental caries,
      malocclusion, developmental anomalies, oral injuries and restorations.
      STATISTICS: Chi-square and Fisher's exact tests of significance were used to
      compare groups. Proportions test was used to compare the significance of the
      parameters between boys and girls. RESULTS: Autistic children with primary
      dentition showed significantly higher incidence of dental caries (24%), when
      compared to other oral conditions. Children with mixed dentition had more
      gingivitis (50%) and children with permanent dentition had more gingivitis
      (48.96%) and malocclusion (71.15%). All the oral conditions were seen more in
      boys than girls. CONCLUSION: Autistic children have significantly poor oral
      hygiene and higher incidence of malocclusion and dental caries when compared to
      other oral conditions.

PMID- 22652210
TI  - Assessment of periodontal status and treatment needs among 12 and 15 years old
      school children in Udaipur, India.
AB  - AIM: To assess and compare the periodontal status and treatment needs among
      school children aged 12 and 15 years in public and private schools of Udaipur,
      India and to provide baseline data for planning and evaluation of oral health
      care promotion programmes. STUDY DESIGN: A cross-sectional descriptive survey.
      METHODS: A survey was conducted on 900 school children aged 12 and 15 years in
      Udaipur. The data were collected by means of clinical examination using the CPITN
      index. STATISTICS: Data was analysed using Pearson's Chi-square and student's t
      test. RESULTS: Children aged 15 years had higher scores of healthy gingiva
      compared with 12 years old. Gender difference of females having better gingival
      health than males was seen in both age groups. Amongst the schools, children in
      private schools had good periodontal status in comparison to public schools. A
      statistically significant association between frequency of tooth brushing and
      CPITN scores was found among children of the 15 year old group. CONCLUSION: There
      is a need for a long term school oral health promotion program to sustain the
      healthy tissues of this growing Indian population.

PMID- 22652211
TI  - Comparative evaluation of the remineralising effects and surface microhardness of
      glass ionomer cement containing grape seed extract and casein phosphopeptide -
      amorphous calcium phosphate: an in vitro study.
AB  - AIM: To evaluate and compare in vitro the remineralising effects and surface
      microhardness of glass ionomer cement (GIC), GIC containing grape seed extract
      and GIC containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP).
      METHODS: An in vitro study with 45 mandibular premolars with standardised class V
      cavities prepared on the buccal and lingual surfaces. Artificial caries-like
      lesions were created and teeth were randomly divided into 3 groups of 15 teeth
      each. Each tooth was sectioned longitudinally into buccal and lingual halves;
      lingual half was used as control and the other as the test specimen. Axial
      longitudinal sections of the control specimens were analysed under polarised
      light microscopy. The experimental halves were restored with 3 materials. Group
      I: glass ionomer cement (GIC), Group II: 10% (w/w) grape seed extract and GIC
      (GSGIC), Group III: 10% (w/w) casein phosphopeptide-amorphous calcium phosphate
      (Recaldent) and GIC (CPPGIC). The restored tooth specimens were exposed to pH
      cycling for 28 days and analysed again for remineralisation under polarised
      microscopy. For the second part of the study, 60 cylindrical specimens (20 each)
      were made using standardised brass moulds and the three experimental materials.
      The specimens were immersed individually in de-ionised water. After 7 days of
      immersion, 10 specimens from each group were subjected to microhardness
      measurements and repeated on the remaining specimens at the end of 30 days.
      STATISTICS: One way ANOVA and post-hoc Tukey's test were used for statistical
      analysis. RESULTS: CPPGIC showed the greatest remineralisation followed by GSGIC
      and least for GIC. Comparisons of microhardness between the three groups were not
      statistically significant. CONCLUSION: Grape seed extract and CPPACP can be used
      for remineralisation of damaged dentine and their incorporation into GIC does not
      compromise the microhardness properties significantly.

PMID- 22652212
TI  - Effect of consuming different dairy products on calcium, phosphorus and pH levels
      of human dental plaque: a comparative study.
AB  - AIM: To determine the calcium, phosphorus and pH levels of human dental plaque
      after consuming different dairy products. METHODS: 68 students (34 with caries
      and 34 caries-free) aged 17-20 years from a private dental college, Moradabad
      city, who agreed to refrain from oral hygiene procedures for 48 hours were
      selected for the study. Calcium and phosphorus levels of harvested dental plaque
      were measured using an electrolyte analyser while plaque pH was measured using a
      digital pH meter after consuming different dairy products (cheese, milk, yogurt)
      and compared with the control (paraffin) group. RESULTS: Cheese and yogurt groups
      showed a statistically significant rise in mean plaque concentrations of calcium
      and phosphorus, whereas milk and control groups showed the least rise in plaque
      concentrations for both caries-active and caries-free subjects. Plaque pH showed
      a stronger correlation with plaque calcium and phosphorus concentrations in both
      caries-active and caries-free subjects. CONCLUSION: Cheese and yogurt without any
      added sugar (sucrose) are non-cariogenic and to some extent cariostatic as they
      increase calcium and phosphorus concentration in dental plaque. Dairy products
      without added sugar can be recommended as after meal desserts, especially to
      school children, which would help to reduce the incidence of dental caries.

PMID- 22652213
TI  - Handpiece and bur skills evaluation during an introductory Clinical Skills
      Programme in a graduate-entry dental school: a pilot study.
AB  - AIM: To assess the effect of an introductory Clinical Skills Program on the
      development of two tasks aimed at teaching a Class II cavity preparation
      technique. STUDY DESIGN: A prospective, observational study. METHODS: Twenty
      three first year students (F: 19; M: 4) were asked to complete two cavities on a
      Frasaco((r)) tooth 46 using a FG 565 pear-shaped diamond bur. Task One: A groove
      was cut from the central fissure area to within 1mm of the marginal ridge which
      was 5mm in length, 2mm in width and 2mm in depth. Task Two: As for Task One and
      in addition, a slot was cut vertically downward at the marginal ridge to create a
      box 2mm in length, 2mm in width and 3mm in depth. Both tasks were undertaken at
      the start of an introductory Clinical Skills course and two months later after
      further skills practice. Cavity dimensions were measured using a digital caliper
      with a depth gauge. STATISTICS: Data were analysed using a two-sample t-test
      (MINITAB((r)) 15.1). RESULTS: Regarding Task One, a statistically-significant
      improvement in groove width was noted (p=0.001). Concerning Task Two, both the
      groove width and the box width improved and both were statistically significant
      p=0.023 and p=0.049, respectively). CONCLUSION: A Clinical Skills Program would
      appear to result in an improvement in cavity preparation, particularly in
      relation to cavity width.

PMID- 22652214
TI  - An atypical presentation of mechanical failure of eruption of a mandibular
      permanent molar: diagnosis and treatment case report.
AB  - BACKGROUND: Failure of eruption of mandibular permanent molars occurs
      infrequently but is a difficult clinical problem. It can be due to local or
      systemic factors or failure of the eruption process. Primary failure of eruption
      (PFE) is a rare condition that can result in severe posterior open bite, requires
      complex treatment strategies and has unfavourable outcomes. Mechanical failure of
      eruption (MFE) is more unusual but can respond positively to treatment.
      Differentiating between the two is crucial in making the correct diagnosis and
      managing the case successfully. CASE REPORT: A 10-year-old girl presented with a
      partially erupted mandibular right first permanent molar, 46. She had no relevant
      medical or dental history and no family history of tooth eruption failure.
      TREATMENT: 46 was monitored for 6 months to allow spontaneous eruption. Local and
      systemic factors were eliminated. Progress radiographs and longitudinal clinical
      data were collected. Attempted eruption of 46 was completed by surgical luxation
      and elevation by orthodontic force. FOLLOW-UP: Surgical luxation and elevation of
      46 was repeated with the removal of the mandibular right second permanent molar,
      47, which was mechanically obstructing the eruption of 46. With continued
      orthodontic force the tooth was righted up and brought into occlusion with no
      complication of ankylosis. The mandibular right third molar continues to erupt
      and migrate mesially. The patient now exhibits a bilateral functioning posterior
      bite three years after the treatment was commenced. CONCLUSION: Through a
      combination of sequential monitoring with treatment including surgical luxation
      and orthodontic force, a therapeutic diagnosis of MFE was made. The appropriate
      treatment was carried out and the tooth erupted into occlusion.

PMID- 22652215
TI  - Antiparasitic agents: new drugs on the horizon.
AB  - The need for new drugs against tropical parasites such as Plasmodium falciparum
      and Trypanosoma brucei is persistent since problems with resistance and toxicity
      are jeopardizing the currently available medicines. Public-private partnerships
      aiming to develop new medicines for malaria and sleeping sickness have, over the
      past 12 years, brought forward several drug candidates that have entered clinical
      trials. These are the synthetic peroxide OZ439 and the spiroindolone NITD609
      against P. falciparum, fexinidazole and the oxaborole SCYX-7158 against T.
      brucei. A further class of high chemotherapeutic potential are the diamidines,
      novel members of which may serve as back-up compounds against trypanosomes and
      other parasites. Thus, finally, new therapeutic agents against malaria and
      sleeping sickness are within reach.

PMID- 22652216
TI  - Nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/chitosan scaffolds for
      skin regeneration.
AB  - The purpose of this study was to evaluate hybrid poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) (PHBV)/chitosan nanofibrous mats as scaffolds for skin
      engineering. In vitro studies were carried out to test the potential of the
      scaffolds for fibroblasts adhesion, viability, and proliferation (L929 cell
      line). The in vivo performance was also studied in a full-thickness wound healing
      model. PHBV/chitosan 4:1 (w/w) exhibited a higher in vitro biocompatibility and a
      better ability for cell adhesion and growth, compared to PHBV/chitosan 2:3 (w/w).
      The in vivo assay also revealed the better performance of this scaffold,
      improving the wound healing process in rats.

PMID- 22652217
TI  - SAXS and ATR-FTIR studies on EBT-TSX mixtures in their sol-gel phases.
AB  - Our previous study demonstrated that mixtures of tamarind seed xyloglucan (TSX)
      with appropriate concentrations of eriochrome black T (EBT) produced a gel that
      could be of benefit for medical use. Here, the sol-gel systems of various fresh
      and aged mixtures were further investigated using rheological measurements. The
      nanostructural changes of EBT-TSX sol-gel phases were analyzed using SAXS. The
      interactions between EBT and TSX in the sol and gel states were examined using
      ATR-FTIR. SAXS data analysis demonstrated that the mixture containing lower
      concentration of EBT formed rod-like structures and that with higher
      concentrations of EBT produced flat particles. The sizes of the TSX structures
      from the aged mixtures in the gel stage were larger than those from the same
      mixtures in the sol state. ATR-FTIR spectral changes revealed that the azo and
      sulfonic acid groups of EBT interacted with the TSX, and the characteristic
      spectrum of the sulfonic acid group of EBT could discriminate between the sol and
      gel state of the EBT-TSX systems. The interactions between EBT and TSX may cause
      conformational changes to TSX and facilitate the sol-gel transition or formation
      of a gel.

PMID- 22652218
TI  - Antiviral activity against dengue virus of diverse classes of algal sulfated
      polysaccharides.
AB  - Diverse classes of sulfated polysaccharides obtained from the red seaweeds
      (Rhodophyta) Grateloupia indica, Scinaia hatei and Gracilaria corticata, the
      brown seaweeds (Phaeophyta) Stoechospermum marginatum and Cystoseira indica and
      the green seaweed (Chlorophyta) Caulerpa racemosa were assayed for antiviral
      activity against the four serotypes of dengue virus (DENV). DENV-2 was the most
      susceptible serotype to all polysulfates, with inhibitory concentration 50%
      values in the range 0.12-20 MUg/mL. The antiviral potency of the sulfated
      polysaccharides depended on the sulfate content, the position of sulfate group,
      the sugar composition, and the molar mass. Independently of the sugar
      composition, the antiviral effect was mainly exerted during DENV-2 adsorption and
      internalization.

PMID- 22652219
TI  - Polysaccharides from Lycium barbarum leaves: isolation, characterization and
      splenocyte proliferation activity.
AB  - The polysaccharides from the fruits of Lycium barbarum have received considerable
      attention in previous publication, but the polysaccharides from the leaves were
      rarely reported. In the present work, four water-soluble polysaccharide
      fractions: LBP-I, LBP-II, LBP-III and LBP-IV isolated from L. barbarum leaves
      were purified through DEAE-Sephadex A-25. LBP-II and LBP-IV respectively showed
      one symmetrical peak on HPGPC with average molecular weight of 9.39 * 104 Da and
      4.18 * 105 Da. UV and IR analysis of the two fractions showed the characteristics
      of acidic polysaccharides combined with polypeptides or proteins. GC analysis
      showed LBP-IV was mainly composed of rhamnose, arabinose, xylose, glucose and
      galactose with molar ratio of 1.61:3.82:3.44:7.54:1.00, and the uronic acid
      content was 47.68% (w/w) determined by sulfuric acid-carbazole method. 1H and 13C
      NMR spectra of LBP-IV also showed the presence of carboxyl carbon and five
      anomeric carbons, and suggested there may be both alpha- and beta-anomeric
      configurations in this fraction. Moreover, splenocyte proliferation activity
      assay showed that LBP-IV significantly enhanced the proliferation of splenocyte
      stimulated by ConA or LPS, indicating the fraction has the beneficial effect on
      immunostimulating activity.

PMID- 22652220
TI  - Anticancer effect of atorvastatin nanostructured polymeric micelles based on
      stearyl-grafted chitosan.
AB  - The purpose of this study was to develop a new therapeutic approach for
      atorvastatin (ATV) adopting nanostructured polymeric micelles for its controlled
      delivery to the cancer cells. Amphiphilic block copolymers of stearyl chitosan
      (SC) and sulfated stearyl chitosan (S-SC) that could self assemble to form
      polymeric micelles with different degree of substitution (DS) were synthesized
      and characterized. The synthesized chitosan derivatives were able to self
      assemble and form micelles encapsulating ATV with critical micellar
      concentrations ranging from 6.9 to 21MUg/ml, drug-loading ranging from 40% to
      84.1% and encapsulation efficiency ranging from 10.4% to 35%. ATV caused a
      significant decrease in particle size and zeta potential of both SC and S-SC
      micelles. Micelles encapsulating ATV exhibited a sustained release and more
      cytotoxic activity against MCF 7 and HCT 116 cell lines than ATV alone. The 50%
      cellular growth inhibition (IC50%) of the drug decreased from 10.4 to 3.7 in case
      of MCF 7 and from 9.4 to 3.4 in case of HCT 116 after its loading in micelles.
      These results indicate that SC ATV polymeric micelles can be considered as a
      promising system for site specific controlled delivery of ATV to tumor cells.

PMID- 22652221
TI  - Class A scavenger receptor promotes cerebral ischemic injury by pivoting
      microglia/macrophage polarization.
AB  - Class A scavenger receptor (SR-A) is primarily expressed in microglia/macrophages
      and plays an important role in immune responses. However, whether SR-A can
      influence microglia/macrophage polarization in cerebral ischemic injury is not
      known. To this end we monitored the phenotypic alteration of
      microglia/macrophages in an animal model of cerebral ischemia injury. SR-A was up
      regulated in mouse brains 24h after permanent occlusion of middle cerebral artery
      (MCAO). SR-A-deficient mice displayed reduced infarct size and improved
      neurological function compared with wild-type mice littermate controls.
      Furthermore, a decrease in inflammatory F4/80(+)CD11b(+)CD45(high)CD11c(+)
      microglia/macrophages and attenuated nuclear factor-kappaB (NF-kappaB) activation
      was found in ischemic brains in the SR-A null mice. This was accompanied by
      alleviation of classically activated M1 macrophage markers and preservation of
      alternatively activated M2 macrophage markers. These data suggest that SR-A
      contributes to cerebral ischemic injury by pivoting the phenotype of
      microglia/macrophages to a skewed M1 polarization.

PMID- 22652222
TI  - Paraventricular and supraoptic nuclei of the hypothalamus mediate cardiovascular
      responses evoked by the microinjection of noradrenaline into the medial
      amygdaloid nucleus of the rat brain.
AB  - The medial amygdaloid nucleus (MeA) is a part of the limbic system and is
      involved in cardiovascular modulation. We previously reported that microinjection
      of noradrenaline (NA) into the MeA of unanesthetized rats caused pressor and
      bradycardiac responses, which were mediated by acute vasopressin release into the
      systemic circulation. In the present study, we tested the possible involvement of
      magnocellular neurons of the paraventricular (PVN) and/or supraoptic (SON) of the
      hypothalamus that synthesize vasopressin in the cardiovascular pathway activated
      by the microinjection of NA into the MeA. Pressor and bradycardiac responses to
      the microinjection of NA (27 nmol/100 nL) into the MeA were blocked by
      pretreatment of either the PVN or the SON with cobalt chloride (CoCl(2), 1 mM/100
      nL), thus indicating that both hypothalamic nuclei mediate the cardiovascular
      responses evoked by microinjection of NA into the MeA. Our results suggest that
      the pressor and bradycardiac response caused by the microinjection of NA into the
      MeA is mediated by magnocellular neurons in both the PVN and SON.

PMID- 22652223
TI  - Hybrids of ravuconazole: synthesis and biological evaluation.
AB  - In continuation of our work on antimicrobial agents, a number of hybrid molecules
      4a-y containing thiazole and triazole pharmacophores were designed and
      synthesized. The structure of the compounds was established by IR, NMR, MS and
      CHN analysis. All the synthesized compounds were tested for qualitative (Zone of
      inhibition) and quantitative (MIC) antimicrobial activities against four
      pathogenic bacteria Bacillus subtilis, Staphylococcus aureus, Escherichia coli
      and Pseudomonas aeruginosa and two pathogenic fungi Candida albicans and
      Aspergillus niger. Of all the synthesized compounds screened, most of them show
      potent antimicrobial activity against Gram positive and Gram negative bacteria as
      well as the fungi species.

PMID- 22652224
TI  - New N-arylamino biquinoline derivatives: synthesis, antimicrobial,
      antituberculosis, and antimalarial evaluation.
AB  - A new series of N-arylamino biquinoline derivatives 5a-x were synthesized by
      reaction of 2-chloro-3-formyl quinolines 2a-d with malononitrile and various
      enhydrazinoketones 4a-f in absolute ethanol. The newly synthesized compounds were
      evaluated for their in vitro antimicrobial activity against a representative
      panel of pathogenic strains and antituberculosis activity against Mycobacterium
      tuberculosis H37Rv. Compounds 5h and 5s exhibited excellent antibacterial
      activity and some of the compounds demonstrated moderate antituberculosis
      activities compared with the first line drugs. The compounds were evaluated in
      vitro for their activity against the growth of Plasmodium falciparum, the malaria
      causing parasite. Some of them showed antimalarial activity with IC(50) values as
      low as 0.005-0.009 MUg/mL.

PMID- 22652225
TI  - A novel class of small-molecule caspase-3 inhibitors prepared by multicomponent
      reactions.
AB  - A series of tetra- and pentasubstituted polyfunctional dihydropyrroles 5 and 6
      were synthesized via practical multicomponent reactions (MCRs) for research on
      their structure-activity relationship as caspase-3 inhibitors. Among 39 compounds
      evaluated, 14 of them exhibited inhibition against caspase-3 with IC(50) ranging
      from 5 to 20 MUM. The inhibitory activities of 5 and 6 depend on the nature of
      substituents on different positions. 5 and 6 possess a different scaffold from
      those previously reported and are the first caspase-3 inhibitors prepared via
      MCRs. The most active compounds 5k (IC(50) = 5.27 MUM) could therefore be used as
      a lead for the development of highly potent caspase-3 inhibitors as drug
      candidates for therapeutic agents by taking advantage of MCRs.

PMID- 22652226
TI  - Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT
      analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors.
AB  - New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were
      synthesized and evaluated for their in vitro activities against HIV-1 in MT-4
      cell cultures. Chemical diversity was introduced in 4 of the six positions of the
      core and the influence of each substituent was studied. This library was built on
      the basis of a rational diversity analysis with the objective of maximizing
      diversity and thus, the activity range with a minimum number of synthesized
      compounds. Among them, 2{1,2,3,1} and 2{1,2,3,4} exhibited the most potent anti
      HIV-1 activities (EC(50)=0.015 MUg/mL; 0.046 MUM, SI >1667) and (EC(50)=0.025
      MUg/mL; 0.086 MUM, SI >1000), respectively, which were about 71-fold and 38-fold
      more active than the reference compound HEPT (EC(50)=1.01 MUg/mL; 3.27 MUM, SI
      >25).

PMID- 22652227
TI  - Visualizing evolution in real time to determine the molecular mechanisms of n
      butanol tolerance in Escherichia coli.
AB  - Toxicity of products or feedstock components poses a challenge in the biocatalyst
      based production of fuels and chemicals. The genetic determinants that are
      involved in increased resistance to an inhibitor form the adaptive landscape for
      the phenotype; so in order to engineer more robust biocatalysts, a better
      understanding of the adaptive landscape is required. Here, we used an adaptive
      laboratory evolution method called visualizing evolution in real time (VERT) to
      help map out part of the adaptive landscape of Escherichia coli tolerance to the
      biofuel n-butanol. VERT enables identification of adaptive events (population
      expansions triggered by adaptive mutants) via visualization of the relative
      proportions of different fluorescently-labeled cells. Knowledge of the occurrence
      of adaptive events allows for a more systematic isolation of adaptive mutants
      while simultaneously reducing the number of missed adaptive mutants (and the
      underlying adaptive mechanisms) that result from clonal interference during the
      course of in vitro evolution. Based on the evolutionary dynamics observed, clonal
      interference was found to play a significant role in shaping the population
      structure of E. coli during exposure to n-butanol, and VERT helped to facilitate
      the isolation of adaptive mutants from the population. We further combined
      adaptive laboratory evolution with genome shuffling to significantly enhance the
      desired n-butanol tolerance phenotype. Subsequent transcriptome analysis of the
      isolated adaptive mutants revealed different mechanisms of n-butanol resistance
      in different lineages. In one fluorescently-marked subpopulation, members of the
      Fur regulon were upregulated; which was not observed in the other subpopulation.
      In addition, genome sequencing of several adaptive mutants revealed the genetic
      basis for some of the observed transcriptome profiles. We further elucidated the
      potential role of the iron-related gene in n-butanol tolerance via overexpression
      and deletion studies and hypothesized that the upregulation of the iron-related
      genes indirectly led to modifications in the outer membrane, which contributed to
      enhanced n-butanol tolerance.

PMID- 22652228
TI  - Cancer detection and primary care...revisited.

PMID- 22652229
TI  - Capecitabine in the treatment of rectal cancer.

PMID- 22652230
TI  - Polyglutamine diseases and the risk of cancer.

PMID- 22652231
TI  - Priorities for cancer prevention.

PMID- 22652232
TI  - A common language in neoadjuvant breast cancer clinical trials: proposals for
      standard definitions and endpoints.
AB  - The neoadjuvant setting provides a unique opportunity to study the effect of
      systemic treatments on breast cancer biology and to identify clinically useful
      prognostic and predictive biomarkers. Discrepancies and inconsistencies in the
      use of definitions and endpoint assessments in this setting confound the analysis
      and interpretation of results across clinical trials and hinder research
      progress. This Review represents a joint effort of the Breast International Group
      and the National Cancer Institute-sponsored North American Breast Cancer Group to
      provide clinicians and researchers with a series of standardised definitions and
      endpoints that could be implemented in future neoadjuvant clinical trials.
      Definitions of the setting of interest and of survival endpoints are recommended,
      together with proposals for standard assessment of the response to treatment, use
      of functional and molecular imaging endpoints, and characterisation and selection
      of the population to treat. We expect that implementation of these
      recommendations will improve the conduct, reporting, and effectiveness of
      clinical trials and fully exploit the clinical and scientific potential of the
      neoadjuvant setting in breast cancer.

PMID- 22652233
TI  - microRNAs in cancer management.
AB  - Since the identification of microRNAs (miRNAs) in 1993, and the subsequent
      discovery of their highly conserved nature in 2000, the amount of research into
      their function--particularly how they contribute to malignancy--has greatly
      increased. This class of small RNA molecules control gene expression and provide
      a previously unknown control mechanism for protein synthesis. As such, it is
      unsurprising that miRNAs are now known to play an essential part in malignancy,
      functioning as tumour suppressors and oncogenes. This Review summarises the
      present understanding of how miRNAs operate at the molecular level; how their
      dysregulation is a crucial part of tumour formation, maintenance, and metastasis;
      how they can be used as biomarkers for disease type and grade; and how miRNA
      based treatments could be used for diverse types of malignancies.

PMID- 22652234
TI  - Short-term androgen deprivation therapy for patients with intermediate-risk
      prostate cancer undergoing dose-escalated radiotherapy: the standard of care?
AB  - What is the best way to manage patients with intermediate-risk prostate cancer?
      One of the most controversial aspects of treatment is the role of short-term
      androgen deprivation therapy in combination with definitive radiotherapy. In two
      randomised trials of patients with mostly intermediate-risk prostate cancer,
      increased overall survival was reported when short-term androgen deprivation
      therapy was added to radiotherapy. However, radiation doses in these studies were
      far below the current standard of care. This limitation, in combination with the
      heterogeneous nature of the cancers classified as intermediate risk, has
      complicated the application of these trial results to modern clinical practice.
      In this Review, we discuss clinical evidence for and against use of short-term
      androgen deprivation therapy with dose-escalated radiotherapy for patients with
      intermediate-risk prostate cancer.

PMID- 22652235
TI  - Optimising radiation treatment decisions for patients who receive neoadjuvant
      chemotherapy and mastectomy.
AB  - Whereas randomised clinical trials have established which patients might benefit
      from postmastectomy radiation therapy after upfront surgery, no such data exist
      for guiding decisions on who might benefit from postmastectomy radiation therapy
      after upfront chemotherapy. Insight must be drawn from non-randomised data to
      provide such guidance. Early data suggest that both extent of disease at
      presentation and response to neoadjuvant chemotherapy predict the risk of
      locoregional recurrence, and can be used to tailor recommendations for
      postmastectomy radiation therapy. Randomised clinical trial data are needed to
      assess whether postmastectomy radiation therapy can be safely omitted in selected
      women with good response to neoadjuvant chemotherapy.

PMID- 22652236
TI  - Reversible laminar signal intensity in deep cortical gray matter in T1-weighted
      images and FLAIR after mild acute hyperammonemic hepatic encephalopathy.
AB  - Soporific acute hyperammonemic hepatic encephalopathy (aHE) can induce
      considerable changes in cerebral white and gray matter. This report describes a
      patient in the subacute phase of aHE grade I without disturbed consciousness and
      with reversible fine laminar cortical involvement on magnetic resonance imaging
      (MRI). The 59-year-old patient had esophageal varices bleeding due to primary
      biliary cirrhosis (ammonium blood level: 140 mmoL/L) and presented with sensory
      Jacksonian seizures, dysarthria, and increased drowsiness and fatigue. MRI
      revealed patchy hyperintense (T2-weighted, T2w) white-matter lesions and
      bilateral signal intensities in the striatum (T1w). During a rise of ammonium
      blood level to 220 mmoL/L, the patient had increased drowsiness, persistent
      dysarthria and mild temporary hemiparesis without loss of consciousness. Two
      weeks later, the patient was asymptomatic and blood ammonium level had reverted
      to normal value. MRI at that time revealed bihemispheric fine laminar subcortical
      hyperintensities on T2w and fluid-attenuated inversion recovery (FLAIR) imaging,
      and partially on T1w sequences, with no swelling or restricted diffusion; the
      hyperintensities were fully reversible a month later. Such a distinct cortical
      signal increase not only on T2w images, but also on T1w, in a patient after a
      mild form of aHE is a new MR finding.

PMID- 22652237
TI  - Bevacizumab as salvage therapy for progressive brain stem gliomas.
AB  - OBJECTIVE: There is no standard of care for patients with progredient brain stem
      gliomas. Therefore, we report about clinical, radiological and metabolic response
      to anti-angiogenic treatment with bevacizumab in a series of 3 patients with
      gliomas involving the brain stem. PATIENTS AND METHODS: Three patients with
      histologically confirmed gliomas involving the brain stem were treated with
      bevacizumab for tumor progression. The clinical data, histopathological findings
      as well as MRI and PET follow up examinations during bevacizumab therapy were
      retrospectively analyzed. RESULTS: The histopathological diagnosis revealed an
      anaplastic astrocytoma WHO grade III in two patients and an astrocytoma WHO grade
      II in 1 patients with clinical and neuroradiological signs of malignization. One
      patient is still progression-free 97 weeks after initiation of bevacizumab
      therapy. Mean progression-free survival and overall survival for the other two
      patients after initiation of bevacizumab therapy was 34.5 weeks and 43.5 weeks.
      During bevacizumab therapy mean KPS improved from 60 to 80 and mean dosage of
      daily dexamathasone was reduced from 7.3 mg to 1.3 mg. MRI showed a decrease of
      T2 weighted hyperintense lesions in all patients and a decrease of contrast
      enhancement in two patients. (18)F-FET-PET showed a decrease of tracer uptake in
      all cases (mean maximum decrease: 25%). CONCLUSION: In this series treatment of
      progressive gliomas involving the brain stem with bevacizumab resulted in an
      improved clinical condition of the patients as well as a reduction of the T2
      weighted lesions and reduced amino acid uptake in the tumor area. It therefore
      may represent a therapeutic salvage option for this type of tumor.

PMID- 22652238
TI  - A systematic review of clinical outcomes, perioperative data and selective
      adverse events related to mild hypothermia in intracranial aneurysm surgery.
AB  - BACKGROUND: In the last two decades, mild intraoperative hypothermia has become
      widely accepted as a protective therapy in neurosurgery. However, its effect in
      intracranial aneurysm surgery remains unclear. OBJECTIVE: The purpose of this
      study was to assess the perioperative effects and selected adverse events
      associated with intraoperative mild hypothermia in aneurysm surgery and to
      compare those with events in normothermic surgery. METHODS: Three literature
      databases, namely the Cochrane Library, PubMed and EMBASE, were searched for
      randomised controlled trials (RCTs) of aneurysm surgery that compared
      intraoperative mild hypothermia and normothermia from January 1965 to August
      2010. Three RCTs were identified. We extracted the following information: author
      names and publication year; clinical outcome (number of deaths and Glasgow
      outcome scales); perioperative data (number of moderate or severe intraoperative
      brain swelling occurrences, hypertensive episodes, ruptured or leaking aneurysms,
      volume of blood loss during surgery, duration of temporary clipping, and number
      of patients who received protective drugs, who required rewarming and who were
      intubated); number of adverse events (cerebral infarctions, brain swelling,
      myocardial ischaemia or infarction, congestive heart failure, meningitis or
      ventriculitis and pneumonia). Except for author names and publication year, the
      data were pooled to perform a mean effect size estimate. The effects of
      intraoperative mild hypothermia were then analysed. RESULTS: The number of
      patients requiring rewarming in the mild hypothermia group was significantly
      greater than in the normothermia group (odds ratio, 33.89; 95% confidence
      intervals, 3.61-318.36). There were no other statistically significant
      differences. CONCLUSION: Based on available RCTs, especially involving surgery of
      low-grade aneurysms, intraoperative mild hypothermia showed no advantages
      compared with normothermia.

PMID- 22652239
TI  - Unusual case of trigeminal neuralgia caused by remote effect of dermoid cyst in
      the ipsilateral cerebellar hemisphere.

PMID- 22652241
TI  - Functional characterization of amyrin synthase involved in ursolic acid
      biosynthesis in Catharanthus roseus leaf epidermis.
AB  - Catharanthus roseus accumulates high levels of the pentacyclic triterpene,
      ursolic acid, as a component of its wax exudate on the leaf surface.
      Bioinformatic analyses of transcripts derived from the leaf epidermis provide
      evidence for the specialized role of this tissue in the biosynthesis of ursolic
      acid. Cloning and functional expression in yeast of a triterpene synthase derived
      from this tissue showed it to be predominantly an alpha-amyrin synthase (CrAS),
      since the alpha-amyrin to beta-amyrin reaction products accumulated in a 5:1
      ratio. Expression analysis of CrAS showed that triterpene biosynthesis occurs
      predominantly in the youngest leaf tissues and in the earliest stages of seedling
      development. Further studies using laser capture microdissection to harvest RNA
      from epidermis, mesophyll, idioblasts, laticifers and vasculature of leaves
      showed the leaf epidermis to be the preferred sites of CrAS expression and
      provide conclusive evidence for the involvement of this tissue in the
      biosynthesis of ursolic acid in C. roseus.

PMID- 22652240
TI  - Atypical category processing and hemispheric asymmetries in high-functioning
      children with autism: revealed through high-density EEG mapping.
AB  - Behavioral evidence for an impaired ability to group objects based on similar
      physical or semantic properties in autism spectrum disorders (ASD) has been
      mixed. Here, we recorded brain activity from high-functioning children with ASD
      as they completed a visual-target detection task. We then assessed the extent to
      which object-based selective attention automatically generalized from targets to
      non-target exemplars from the same well-known object class (e.g., dogs). Our
      results provide clear electrophysiological evidence that children with ASD (N=17,
      aged 8-13 years) process the similarity between targets (e.g., a specific dog)
      and same-category non-targets (SCNT) (e.g., another dog) to a lesser extent than
      do their typically developing (TD) peers (N=21). A closer examination of the data
      revealed striking hemispheric asymmetries that were specific to the ASD group.
      These findings align with mounting evidence in the autism literature of anatomic
      underconnectivity between the cerebral hemispheres. Years of research in
      individuals with TD have demonstrated that the left hemisphere (LH) is
      specialized toward processing local (or featural) stimulus properties and the
      right hemisphere (RH) toward processing global (or configural) stimulus
      properties. We therefore propose a model where a lack of communication between
      the hemispheres in ASD, combined with typical hemispheric specialization, is a
      root cause for impaired categorization and the oft-observed bias to process local
      over global stimulus properties.

PMID- 22652242
TI  - Phytochemical and biological studies of bryophytes.
AB  - The bryophytes contain the Marchantiophyta (liverworts), Bryophyta (mosses) and
      Anthocerotophyta (hornworts). Of these, the Marchantiophyta have a cellular oil
      body which produce a number of mono-, sesqui- and di-terpenoids, aromatic
      compounds like bibenzyl, bis-bibenzyls and acetogenins. Most sesqui- and di
      terpenoids obtained from liverworts are enantiomers of those found in higher
      plants. Many of these compounds display a characteristic odor, and can have
      interesting biological activities. These include: allergenic contact dermatitis,
      antimicrobial, antifungal and antiviral, cytotoxic, insecticidal, insect
      antifeedant, superoxide anion radical release, 5-lipoxygenase, calmodulin,
      hyaluronidase, cyclooxygenase, DNA polymerase beta, and alpha-glucosidase and NO
      production inhibitory, antioxidant, piscicidal, neurotrophic and muscle relaxing
      activities among others. Each liverwort biosynthesizes unique components, which
      are valuable for their chemotaxonomic classification. Typical chemical structures
      and biological activity of the selected liverwort constituents as well as the
      hemi- and total synthesis of some biologically active compounds are summarized.

PMID- 22652243
TI  - Suppression of camptothecin biosynthetic genes results in metabolic modification
      of secondary products in hairy roots of Ophiorrhiza pumila.
AB  - Camptothecin is a monoterpenoid indole alkaloid that exhibits anti-tumor
      activity. In Ophiorrhiza pumila, production of camptothecin and its related
      alkaloids was high in the hairy roots, but not in the cell suspension culture
      derived from hairy roots. To identify the intermediates in camptothecin
      biosynthesis, expression of genes encoding tryptophan decarboxylase (TDC) and
      secologanin synthase (SLS), the two enzymes catalyzing the early steps in
      camptothecin biosynthesis, were suppressed in the hairy roots of O. pumila by RNA
      interference (RNAi), and metabolite changes were investigated. In most TDC- and
      SLS-suppressed lines, accumulation of camptothecin and related alkaloids,
      strictosidine, strictosamide, pumiloside, and deoxypumiloside was reduced. The
      accumulation levels of secologanin exhibited a strong negative correlation with
      the expression level of TDC, and that of loganin exhibited a negative correlation
      with the expression level of SLS. Some hairy root-specific chromatographic peaks
      detected by liquid chromatography Fourier transform ion cyclotron resonance mass
      spectrometry (LC-FTICR-MS) exhibited positive or negative correlation with TDC
      expression, suggesting their possible involvement in camptothecin biosynthesis.

PMID- 22652244
TI  - Gender differences in knowledge and health beliefs related to behavioral
      intentions to prevent human papillomavirus infection.
AB  - This study assessed gender differences in human papillomavirus (HPV) awareness
      (including knowledge), health beliefs, and behavioral intentions to prevent
      infection. The participants comprised 763 and 905 sexually active men and women,
      respectively. Gender differences were observed in HPV knowledge, health beliefs,
      and sociodemographics that were significantly correlated with behavioral
      intentions to prevent infection. There were gender differences in the factors
      related to behavioral intentions to prevent HPV. In multiple regression analysis,
      HPV knowledge was not related to behavioral intentions, whereas perceived
      benefits were related to behavioral intentions consistently among men and women,
      while the effects of perceived barriers were inconsistent. HPV awareness was very
      low regardless of gender. While HPV education is urgently required for men,
      enhancing HPV awareness, reinforcing positive perceptions of HPV prevention, and
      reducing unhealthy sexual behaviors are necessary for the entire Korean
      population.

PMID- 22652245
TI  - Family function of the families consisting of Asian immigrant women living in
      South Korea: a 3-year longitudinal study.
AB  - Marriages between Korean men and immigrant women from elsewhere in Asia have
      increased rapidly during recent years. The aim of this study was to analyze the
      relationship within families consisting of immigrant women and to identify the
      relevant factors. The study subjects were 62 Asian immigrant women married to
      South Korean men living in South Korea. In a baseline study in August 2008, the
      socioeconomic factors and family APGAR (adaptation, partnership, growth,
      affection, and resolve) scores were measured. Family APGAR has been widely used
      to study the relationship of family function and health problems in the busy
      clinician's office. A 3-year follow-up study was then conducted in August 2011,
      and the results were compared with the baseline study results. Family APGAR
      scores were higher at the 3-year follow-up than those at baseline. Changes in
      family APGAR scores were found to be influenced by the birthplace, reported
      subjective ability to read Korean, and Center for Epidemiologic Studies
      Depression Scale score. 

PMID- 22652246
TI  - Cervical and anal human papillomavirus infection in adult women in American
      Samoa.
AB  - The prevalence of cervical and anal human papillomavirus (HPV) and risk factors
      associated with infections were evaluated in a cross-sectional study of 211 adult
      women in American Samoa. Overall, 53% of women reported ever having a Pap smear.
      Cervical and anal HPV was detected in 10% and 16% of women, respectively; 4% of
      women had concurrent cervical and anal HPV. The most common cervical genotypes
      were HPV 6, HPV 16, and HPV 53. Cutaneous HPV types were detected in 40% of anal
      infections. Cervical HPV infection was associated with anal HPV (age-adjusted
      odds ratio = 3.32, 1.10-10.00). After age adjustment, cervical HPV was associated
      with being unmarried, postsecondary education, hot running water at home,
      multiple sexual partners, nulliparity, condom use, and other contraceptive
      methods. In multivariate analyses, only age remained associated with cervical HPV
      and anal HPV. Cervical and anal HPV was more prevalent among younger women; only
      anal HPV was detected in older women.

PMID- 22652247
TI  - Maternal autonomy and child health care utilization in India: results from the
      National Family Health Survey.
AB  - The objective of this study was to examine the association of maternal autonomy
      with preventive and curative child health care utilization in India. Data from
      the National Family Health Survey 2005-2006 were used to ascertain association of
      maternal autonomy (in 3 dimensions: decision making, access to financial
      resources, freedom of movement) with child's primary immunization status
      (indicative of preventive health care use) and treatment seeking for child's
      acute respiratory infection (indicative of curative health care use). Low
      maternal freedom of movement was associated with higher odds of incomplete
      primary immunization of the child and for not seeking treatment for the child's
      acute respiratory infection. Low maternal financial access was associated with
      increased odds for incomplete primary immunization of the child. The findings
      show that improvement in autonomy of Indian mothers, especially their freedom of
      movement, may help improve utilization of health care for their children. 

PMID- 22652248
TI  - The alcohol dehydrogenase 1C(rs698) genotype and breast cancer: a meta-analysis.
AB  - Published data regarding the association between alcohol dehydrogenase (ADH) 1C
      genotypes and breast cancer risk show conflicting results. The authors performed
      this meta-analysis on 1969 patients and 2244 controls from 4 (including 7 study
      populations) related case-control studies to estimate the association between
      ADH1C(rs698) genotyping information and breast cancer risk. According to the 6
      eligible populations, the odds ratios (ORs) and 95% confidence intervals (CIs)
      for breast cancer risk for ADH1C (1-2) versus ADH1C (2-2) , ADH1C (1-1) versus
      ADH1C (2-2) genotype, and ADH1C (1) versus ADH1C (2) were 1.16 (0.95-1.42), 1.17
      (0.95-1.44), and 1.05 (0.96-1.16), respectively. The OR (95% CI) for ADH1C (1-1)
      + ADH1C (1-2) versus ADH1C (2-2) from the 7 study populations was 1.14 (0.96
      1.36). Meanwhile, genotypes of ADH1C (1-1) + ADH1C (1-2) increased the risk of
      breast cancer in drinkers (OR = 1.35; 95% CI = 1.03-1.76). This meta-analysis
      suggested that the ADH1C (1) allele might modestly influence the effect of
      alcohol on breast cancer but is not an independent risk factor for breast cancer.
      However, more restricted prospective studies are needed. 

PMID- 22652249
TI  - Growth curves for school children from Kuching, Sarawak: a methodological
      development.
AB  - In this article, the authors propose reference curves for height and weight for
      school children in the Kuching area, Sarawak. The school children were from
      primary to secondary schools (aged 6.5 to 17 years old) and comprised both
      genders. Anthropometric measurements and demographic information for 3081 school
      aged children were collected (1440 boys and 1641 girls). Fitted line plots and
      percentiles for height and weight (3rd, 10th, 25th, 50th, 75th, 90th, and 97th
      percentiles) were obtained. The height of school boys and school girls were
      almost similar at the start of their school-going age. For school girls, height
      and weight values stabilized when they reached 16 or 17 years old but kept
      increasing for school boys. School boys were taller than school girls as they
      entered adolescence. Height differences between school boys and school girls
      became significantly wider as they grew older. Chinese school children were
      taller and heavier than those of other ethnic groups. 

PMID- 22652250
TI  - Why do Bangladeshi people use smokeless tobacco products?
AB  - Despite scientific evidence about the harmful effects of smokeless tobacco (SLT),
      it is widely used in Bangladesh. This study explored perceptions about health
      effects of SLT use. Semistructured interviews were conducted with 1812 nonsmoking
      adults. About 40% of the participants were current SLT users or had used SLT in
      the past. Family members' influence was the main factor for initiation. The
      participants believed that people continued using SLT because of addiction (52%)
      and as a part of their lifestyle (23%). The majority of participants (77%) did
      not mention any benefit, but SLT users considered it to be a remedy for toothache
      (P < .05). Almost all participants mentioned that SLT was harmful and causes
      heart disease, cancer, and tuberculosis. Doctors' advice was the common
      motivating factor to quit. Health promotion interventions should highlight the
      adverse effects of SLT use, which outweigh the perceived benefits, and should
      consider addressing the role of family in SLT initiation and use. 

PMID- 22652251
TI  - Treatment outcome of multidrug-resistant Mycobacterium tuberculosis in Nepal.
AB  - The purpose of this study was to examine factors associated with treatment
      outcome of multidrug-resistant tuberculosis (MDR-TB) cases in Nepal. A
      retrospective analysis of MDR-TB cases by demographic determinants and treatment
      was conducted. A total of 494 MDR-TB cases were registered from 2005 to 2008,
      with data obtained from the National Tuberculosis Center. Chi-squared tests were
      used to assess statistically the association between smear and culture conversion
      and treatment outcome. Determinants were analyzed with the use of Kaplan-Meier
      curves and Cox proportional hazards models to generate estimates of the
      associations with the time to treatment outcome. Sputum conversion status and
      culture conversion status were positively associated with treatment outcome for
      MDR-TB. In a multiple Cox proportional hazards regression model, no determinants
      were found to be associated with time to cure.

PMID- 22652252
TI  - Equity of access under Korean universal health insurance.
AB  - This study examined the extent to which equity in the use of physician services
      has been achieved in the Republic of Korea. Descriptive and logistic regression
      analysis was performed examining the relationship between the dependent variable
      and the independent variables and the relative importance of factors. The results
      indicate that a universal health insurance system has not yielded a fully
      equitable distribution of services. Access differences arise from coverage
      limitation, as well as urban/rural variations in the distributions of providers.
      The policy options for expansion of coverage should be encouraged to ease the
      financial burden of out-of-pocket payments on patients and to limit the range of
      noninsured services. Urban/rural variations in the distributions of providers are
      caused by the government's "laissez-faire" policy for the private medical sector.
      To solve this geographic misdistribution, the attention of policy makers is
      required, with changing of the government's "laissez-faire" policy. 

PMID- 22652253
TI  - Validity of the Malay version of the Internet Addiction Test: a study on a group
      of medical students in Malaysia.
AB  - The use of the Internet has been increasing dramatically over the decade in
      Malaysia. Excessive usage of the Internet has lead to a phenomenon called
      Internet addiction. There is a need for a reliable, valid, and simple-to-use
      scale to measure Internet addiction in the Malaysian population for clinical
      practice and research purposes. The aim of this study was to validate the Malay
      version of the Internet Addiction Test, using a sample of 162 medical students.
      The instrument displayed good internal consistency (Cronbach's alpha = .91),
      parallel reliability (intraclass coefficient = .88, P < .001), and concurrent
      validity with the Compulsive Internet Use Scale (Pearson's correlation = .84, P <
      .001). Receiver operating characteristic analysis showed that 43 was the optimal
      cutoff score to discriminate students with and without Internet dependence.
      Principal component analysis with varimax rotation identified a 5-factor model.
      The Malay version of the Internet Addiction Test appeared to be a valid
      instrument for assessing Internet addiction in Malaysian university students. 

PMID- 22652254
TI  - Beta-carboline alkaloids derived from the ascidian Synoicum sp.
AB  - Six beta-carboline alkaloids (1-6) of the eudistomin Y class were isolated from
      the Korean ascidian Synoicum sp. These compounds were chemically converted to a
      known compound, eudistomin Y(1) (7) and six new derivatives, designated
      eudistomins Y(8)-Y(13) (8-13). Several of these natural and synthetic compounds
      exhibited moderate to significant antimicrobial activity, weak cytotoxic
      activity, and inhibitory activities toward sortase A, isocitrate lyase, and
      Na(+)/K(+)-ATPase. Structure-activity relationships were also deduced.

PMID- 22652255
TI  - C-Aryl 5a-carba-beta-d-glucopyranosides as novel sodium glucose cotransporter 2
      (SGLT2) inhibitors for the treatment of type 2 diabetes.
AB  - C-Aryl 5a-carba-beta-d-glucopyranose derivatives were synthesized and evaluated
      for inhibition activity against hSGLT1 and hSGLT2. Modifications to the
      substituents on the two benzene rings resulted in enhanced hSGLT2 inhibition
      activity and extremely high hSGLT2 selectivity versus SGLT1. Using the created
      superimposed model, the reason for the high hSGLT2 selectivity was speculated to
      be that additional substituents occupied a new space, in a different way than
      known inhibitors. Among the tested compounds, the ethoxy compound 5h with high
      hSGLT2 selectivity exhibited more potent and longer hypoglycemic action in db/db
      mice than our O-carbasugar compound (1) and sergliflozin (2), which could be
      explained by its improved PK profiles relative to those of the two compounds.
      These results indicated that 5h might be a promising drug candidate for the
      treatment of type 2 diabetes.

PMID- 22652256
TI  - Preparation of giant unilamellar vesicles from damp lipid film for better lipid
      compositional uniformity.
AB  - Giant unilamellar vesicles (GUVs) containing cholesterol often have a wide
      distribution in lipid composition. In this study, GUVs of 1,2-dioleoyl-sn-glycero
      3-phosphocholine(DOPC)/1,2-distearoyl-sn-glycero-3
      phosphocholine(DSPC)/cholesterol and 1,2-diphytanoyl-sn-glycero-3
      phosphocholine(diPhyPC)/1,2-dipalmitoyl-sn-glycero-3
      phosphocholine(DPPC)/cholesterol were prepared from dry lipid films using the
      standard electroformation method as well as a modified method from damp lipid
      films, which are made from compositional uniform liposomes prepared using the
      Rapid Solvent Exchange (RSE) method. We quantified the lipid compositional
      distributions of GUV by measuring the miscibility transition temperature of GUVs
      using fluorescence microscopy, since a narrower distribution in the transition
      temperature should correspond to a more uniform distribution in GUV lipid
      composition. Cholesterol molecules can demix from other lipids in dry state and
      form cholesterol crystals. Using optical microscopy, micron-sized crystals were
      observed in some dry lipid films. Thus, a major cause of GUV lipid compositional
      heterogeneity is the demixing of lipids in the dry film state. By avoiding the
      dry film state, GUVs prepared from damp lipid films have a better uniformity in
      lipid composition, and the standard deviations of miscibility transition
      temperature are about 2.5 times smaller than that of GUVs prepared from dry lipid
      films. Comparing the two ternary systems, diPhyPC/DPPC/cholesterol GUVs has a
      larger cholesterol compositional heterogeneity, which directly correlates with
      the low maximum solubility of cholesterol in diPhyPC lipid bilayers (40.2+/
      0.5mol%) measured by light scattering. Our data indicate that cholesterol
      interacts far less favorably with diPhyPC than it does with other PCs. The damp
      lipid film method also has a potential of preparing GUVs from cell membranes
      containing native proteins without going through a dry state.

PMID- 22652257
TI  - Vanillin and ferulic acid: not the major degradation products of curcumin.

PMID- 22652258
TI  - [News in management of colorectal cancer at JFHOD 2012 meeting].
AB  - All aspects of the management of colorectal cancer were presented during the 2012
      edition of JFHOD meeting, from screening to new drugs tested in metastatic
      situation. It was confirmed that an average number of more than 0.8 detected
      polyps was a quality criteria of screening colonoscopies performed for positive
      Hemoccult((r)). The superiority of brush-sampling fecal immunological test
      compared to guaiac fecal occult blood test has been demonstrated in two studies,
      with doubled and tripled detection rates of invasive cancers and advanced
      adenomas, respectively. Reproducibility is a major quality factor of the
      histopathological analysis of malignant colorectal polyps treated by endoscopic
      polypectomy. The inter-observer concordance was satisfying for the invasion depth
      and the resection margins, but inadequate for the degree of differentiation, the
      budding, the degree of submucosal infiltration and vascular embol. Reliability
      was enhanced by the importance of the endoscopic activity in center and by the
      orientation of the polyps. Ultrasonographic evidence of downsizing after
      neoadjuvant radiochemotherapy in rectal cancer was predictive of better survival.
      In a randomized trial, neoadjuvant radiochemotherapy was more toxic in patients
      older than 70 years, inducing a decreased frequency of surgery and more frequent
      permanent colostomy. After retrospective analysis of individual data from
      patients with synchronous metastases included in four clinical trials, the
      resection of the primary tumor was an independent predictive factor of overall
      and progression free survival. A prospective randomized trial must confirm this
      result. A study confirmed the important contribution of diffusion-weighted MRI in
      the preoperative evaluation of liver metastases. Promising data were presented
      concerning the intensification of chemotherapy, hepatic intra-arterial
      chemotherapy and integration of targeted therapies to increase the resectability
      rate of metastases. In palliative setting, the promising action of two tyrosine
      kinase inhibitors (sorafenib and nintedanib) in phase I-II studies will warrant
      further clinical development.

PMID- 22652259
TI  - Recent advances on multidimensional liquid chromatography-mass spectrometry for
      proteomics: from qualitative to quantitative analysis--a review.
AB  - With the acceleration of proteome research, increasing attention has been paid to
      multidimensional liquid chromatography-mass spectrometry (MDLC-MS) due to its
      high peak capacity and separation efficiency. Recently, many efforts have been
      put to improve MDLC-based strategies including "top-down" and "bottom-up" to
      enable highly sensitive qualitative and quantitative analysis of proteins, as
      well as accelerate the whole analytical procedure. Integrated platforms with
      combination of sample pretreatment, multidimensional separations and
      identification were also developed to achieve high throughput and sensitive
      detection of proteomes, facilitating highly accurate and reproducible
      quantification. This review summarized the recent advances of such techniques and
      their applications in qualitative and quantitative analysis of proteomes.

PMID- 22652260
TI  - Multivariate curve resolution combined with gas chromatography to enhance
      analytical separation in complex samples: a review.
AB  - This review describes the major advantages and pitfalls of iterative and non
      iterative multivariate curve resolution (MCR) methods combined with gas
      chromatography (GC) data using literature published since 2000 and highlighting
      the most important combinations of GC coupled to mass spectrometry (GC-MS) and
      comprehensive two-dimensional gas chromatography with flame ionization detection
      (GC*GC-FID) and coupled to mass spectrometry (GC*GC-MS). In addition, a brief
      summary of some pre-processing strategies will be discussed to correct common
      issues in GC, such as retention time shifts and baseline/background
      contributions. Additionally, algorithms such as evolving factor analysis (EFA),
      heuristic evolving latent projection (HELP), subwindow factor analysis (SFA),
      multivariate curve resolution-alternating least squares (MCR-ALS), positive
      matrix factorization (PMF), iterative target transformation factor analysis
      (ITTFA) and orthogonal projection resolution (OPR) will be described in this
      paper. Even more, examples of applications to food chemistry, lipidomics and
      medicinal chemistry, as well as in essential oil research, will be shown. Lastly,
      a brief illustration of the MCR method hierarchy will also be presented.

PMID- 22652261
TI  - Chemometric evaluation of different experimental conditions on wheat (Triticum
      aestivum L.) development using liquid chromatography mass spectrometry (LC-MS)
      profiles of benzoxazinone derivatives.
AB  - Different chemometric techniques have been used to evaluate the effect of
      distinct experimental conditions and factors on Triticum aestivum L. plant
      development. The study was conducted using three wheat varieties, Astron, Ritmo
      and Stakado. These varieties were grown under organic and conventional
      cultivation systems. Samples were collected at five growth stages. Shoots and
      roots of each plant at these stages were analysed. Three replicates of each
      analysed sample were performed to improve representativeness and to allow for the
      evaluation of natural variability and interaction effects. All samples were
      analysed using Liquid Chromatography Mass-Spectrometry (LC-MS), and the Total Ion
      Current (TIC) profiles of benzoxazinone derivatives obtained for each sample were
      investigated. Qualitative and quantitative assessments of these TIC profiles and
      of their changes in the analysed samples were carried out using different
      chemometric techniques. Estimation of main effects, and of their possible
      interaction, was performed by means of Analysis of Variance combined to Principal
      Component Analysis (ANOVA-PCA) and of Analysis of Variance combined to
      Simultaneous Component Analysis (ASCA).

PMID- 22652262
TI  - Optimization of antibiotic analysis in water by solid-phase extraction and high
      performance liquid chromatography-mass spectrometry/mass spectrometry.
AB  - This paper describes the development of an optimized method based on solid-phase
      extraction (SPE) followed by liquid chromatography-electrospray ionization tandem
      mass spectrometry (LC-MS/MS) for the simultaneous analysis of ten antibiotic
      compounds including tetracyclines, sulfonamides, macrolides and quinolones. LC
      MS/MS sensitivity has been optimized by alterations to both LC and MS operations.
      Of the two high resolution columns tested, Waters Symmetry C(18) endcapped and
      Agilent Zorbax Bonus-RP, the latter was found to show better performance in
      producing sharp peaks and clear separation for most of the target compounds.
      Optimization of the MS fragmentation collision and cone energy enhanced the peak
      areas of the target analytes. The recovery of the target compounds from water
      samples was most efficient on Waters Oasis HLB SPE cartridge, while methanol was
      shown to be the most suitable solvent for desorbing the compounds from SPE. In
      addition, acidification of samples prior to SPE was shown to enhance the recovery
      of the compounds. To ensure a satisfactory recovery, the flow rate through SPE
      should be maintained at <=10 mL min(-1). The method was successfully applied to
      the analysis of antibiotics from environmental water samples, with concentrations
      being <LOD in tap water, between <LOD to 28 ng L(-1) in river water and between
      <LOD to 230 ng L(-1) in sewage effluent.

PMID- 22652263
TI  - Molecularly imprinted polymer coated solid-phase microextraction fiber prepared
      by surface reversible addition-fragmentation chain transfer polymerization for
      monitoring of Sudan dyes in chilli tomato sauce and chilli pepper samples.
AB  - Surface reversible addition-fragmentation chain transfer (RAFT) polymerization
      method was firstly applied to the preparation of molecularly imprinted polymer
      (MIP) coated silicon solid-phase microextraction (SPME) fibers. With Sudan I as
      template, an ultra-thin MIP coating with about 0.55-MUm thickness was obtained
      with homogeneous structure and controlled composition, due to the controllable
      radical growing and chain propagation in surface RAFT polymerization. The MIP
      coated fibers were found with enhanced selectivity coefficients (3.0-6.5) to
      Sudan I-IV dyes in contrast with those reported in our previous work.
      Furthermore, the ultra-thin thickness of MIP coating was helpful to the effective
      elution of template and fast adsorption/desorption kinetics, so only about 18 min
      was needed for MIP-coated SPME operation. The detection limits of 21-55 ng L(-1)
      were achieved for four Sudan dyes, when MIP-coated SPME was coupled with liquid
      chromatography (LC) and mass spectrometry (MS) detection. The MIP-coated SPME-LC
      MS/MS method was tested for the monitoring of ultra trace Sudan dyes in spiked
      chilli tomato sauce and chilli pepper samples, and high enrichment effect,
      remarkable matrix peaks-removing capability, and consequent high sensitivities
      were achieved to four Sudan dyes.

PMID- 22652264
TI  - Quantitative selenium speciation in human urine by using liquid chromatography
      electrospray tandem mass spectrometry.
AB  - A liquid chromatography-electrospray-tandem mass spectrometry (ES-MS/MS) method
      was developed for the speciation analysis of four organic selenium species of
      relevance to human urinary metabolism, namely trimethylselenomium ion (TMSe(+)),
      selenomethionine (SeMet) and the two selenosugars, methyl 2-acetamido-2-deoxy-1
      seleno-beta-D-galactos/-glucos-amine (SeGalNAc and SeGluNAc, respectively). Their
      chromatographic separation was achieved by using a cation exchange pre-column
      coupled in-series with a reversed-phase high-performance liquid chromatography
      column, along with an isocratic mobile phase. Online detection was performed
      using ES-MS/MS in selective reaction monitoring mode. SeGalNAc was detected as
      the major human urinary metabolite of selenium in the samples analysed, whereas
      TMSe(+) was detected in the urine of one volunteer before and after receiving a
      selenium supplement. SeMet was not detected as a urine excretory metabolite in
      this study. Spiking experiments performed with the urine samples revealed
      significant signal suppression caused by coeluting matrix constituents. To
      overcome such interferences, isotopically labelled (13)CD(3)(82)SeGalNAc was used
      as an internal standard, whereas in the absence of an isotopically labelled
      internal standard for TMSe(+), the standard addition method was applied. Quality
      control for the accurate quantitation of TMSe(+) and SeGalNAc was carried out by
      analysing spiked human urine samples with appropriate selenium standards over a
      concentration range of 10-50 MUg Se L(-1). The method has achieved a limit of
      detection in the presence of urine matrix comparable to that of HPLC-inductively
      coupled plasma-mass spectrometry for the four selenium species: 1.0 MUg Se L(-1)
      for TMSe(+), 5.6 MUg Se L(-1) for SeMet, and 0.1 MUg Se L(-1) for both SeGalNAc
      and SeGluNAc.

PMID- 22652265
TI  - Integrated rapid resolution liquid chromatography-tandem mass spectrometric
      approach for screening and identification of metabolites of the potential
      anticancer agent 3,6,7-trimethoxyphenanthroindolizidine in rat urine.
AB  - An integrated approach combining data acquisition using MS(E) and multi-period
      product ion scan (mpMS/MS), with high-resolution characteristic extracted ion
      chromatograms (hcXIC) as a data mining method, was developed for in vivo drug
      metabolites screening and identification. This approach is illustrated by
      analyzing metabolites of a potential anticancer agent, 3,6,7
      trimethoxyphenanthroindolizidine (CAT) in rat urine based on rapid resolution
      liquid chromatography combined with tandem mass spectrometry (RRLC-MS/MS).
      Untargeted full-scan MS(E) enabled the high-throughput acquisition of potential
      metabolites, and targeted mpMS/MS contributed to the sensitivity and specificity
      of the acquisition of molecules of interest. The data processing method hcXIC,
      based on the structure of CAT, was shown to be highly effective for the
      metabolite discovery. Through the double-filtering effect of the characteristic
      ion and accurate mass, conventional extracted ion chromatograms that contained a
      substantial number of false-positive peaks were simplified into chromatograms
      essentially free of endogenous interferences. As a result, 21 metabolites were
      detected in rat urine after oral administration of CAT. Based on the
      characteristic fragmentation patterns of the phenanthroindolizidine alkaloid, the
      structures of 9 metabolites were identified. Furthermore, the interpretation of
      the MS/MS spectra of these metabolites enabled the determination of demethylation
      position as well as the differentiation between N-oxidized and hydroxylated
      metabolites.

PMID- 22652266
TI  - Highly sensitive and selective detection of biothiols using graphene oxide-based
      "molecular beacon"-like fluorescent probe.
AB  - A fluorometric method for quantity analysis of biothiols was developed using a
      graphene oxide (GO)-based "molecular beacon"-like probe, which consisted of FITC
      labeled thymine (T)-rich single-stranded DNA (ssDNA), GO and Hg(2+) ions. The
      labeled ssDNA containing T-T mismatches would self-hybridize to duplex in the
      presence of Hg(2+), which can avoid its adsorption on GO and the fluorescence of
      this GO-based probe was recovered. The fluorescence of the probe quenched after
      the addition of biothiols such as glutathione (GSH) and cysteine (Cys) owing to
      thiol groups can selectively competitive ligation of Hg(2+) ions with T-T
      mismatches. In the present work, the GO-based probe was used for the
      determination of GSH and Cys. Under the optimal conditions, a linear correlation
      was established between fluorescence intensity ratio I(0)/I and the concentration
      of GSH in the range of 2.0*10(-9)-5.0*10(-7) mol L(-1) with a detection limit of
      1.0*10(-9) mol L(-1). The linear range for Cys is from 5.0*10(-9) to 4.5*10(-7)
      mol L(-1) with a detection limit of 2.0*10(-9) mol L(-1). The proposed method was
      applied to the determination of GSH in human serum and cell extract samples with
      satisfactory results.

PMID- 22652267
TI  - Novel, highly selective detection of Cr(III) in aqueous solution based on a gold
      nanoparticles colorimetric assay and its application for determining Cr(VI).
AB  - A simple, rapid, sensitive and field-portable colorimetric technique for the
      determination of Cr(III) in aqueous solution based on an aggregation-induced
      color transition of gold nanoparticles (AuNPs) has been developed. AuNPs were
      first functionalized with a dithiocarbamate-modified N-benzyl-4-(pyridin-4
      ylmethyl)aniline ligand (BP-DTC). Chelation of Cr(III) by several of these
      ligands, bound to different nanoparticles, led to nanoparticle aggregation in
      solution. This gave rise to a color change from wine-red to blue that was
      discernible by the naked eye and an easily measurable alteration in the
      extinction spectrum of the particles. The method could be used to determine
      Cr(III) with a detection limit of 31 ppb. Furthermore, selective detection of
      trace Cr(III) in aqueous solution in the presence of 12 other transition metal
      ions has been achieved. Toward the goal of practical applications, the sensor has
      been further evaluated with a view to monitoring Cr(III) in nutritional
      supplements and the blood of diabetes patients and also applied in the indirect
      determination of Cr(VI) in waste water.

PMID- 22652268
TI  - Dynamic properties of the polyethylene glycol molecules on the oscillating solid
      liquid interface.
AB  - The dynamic properties of polyethylene glycol (PEG) molecules on the solid-liquid
      interface oscillating at MHz were investigated using the quartz crystal
      microbalance (QCM). The number-average molecular weights (M(n)) of the PEG
      molecules were systematically varied over 4 orders of magnitude. This study makes
      it clear that the series-resonant frequency shift, DeltaF, of the QCM against the
      square root of the density-viscosity product of the PEG solution is linear and
      has the intercept. Moreover, systematical analysis reveals that the DeltaF slope
      rapidly decreases with M(n) and that the DeltaF intercept becomes constant above
      4.0*10(3) g mol(-1). As a result, those reveal that the resonant length of the
      PEG molecule moving with the oscillating plate of 9 MHz is 54.2 A. We also find
      that the behaviors of DeltaF due to M(n) are mainly caused by the length of the
      PEG molecule.

PMID- 22652269
TI  - High-performance closed-tube PCR based on switchable luminescence probes.
AB  - We introduce a switchable lanthanide luminescence reporter technology based
      closed-tube PCR for the detection of specific target DNA sequence. In the
      switchable lanthanide chelate complementation based reporter technology
      hybridization of two nonfluorescent oligonucleotide probes to the adjacent
      positions of the complementary strand leads to the formation of a highly
      fluorescent lanthanide chelate complex. The complex is self-assembled from a
      nonfluorescent lanthanide chelate and a light-harvesting antenna ligand when the
      reporter molecules are brought into close proximity by the oligonucleotide
      probes. Outstanding signal-to-background discrimination in real-time PCR assay
      was achieved due to the very low background fluorescence level and high specific
      signal generation. High sensitivity of the reporter technology allows the
      detection of a lower concentration of amplified DNA in the real-time PCR,
      resulting in detection of the target at the earlier amplification cycle compared
      to commonly used methods.

PMID- 22652270
TI  - Neuroconnectivity and valproic acid: the myelin hypothesis.
AB  - Neuropsychiatric medications that directly alter the epigenome, such as valproic
      acid, can under certain conditions reactivate critical developmental periods and
      thus impact adult neuroconnectivity. In animal models valproic acid was shown to
      inhibit the process of postnatal myelination and to replicate age-dependent
      decline in remyelination efficiency. The human central nervous system's
      myelination process, unlike that of non-human primates commonly used in the
      experimental models, is an intricate heterochronous process that continues well
      into adult life and which probably underlies later life neurocognitive changes
      and plasticity. Chronic exposure to valproic acid, especially in patients with
      epilepsy and neuropsychiatric disorders, may profoundly affect this process and
      its developmental trajectory. Further studies using novel MRI methods that allow
      in vivo mapping of myelination trajectories across the lifespan are urgently
      required to address the potential effects of valproic acid on brain development.

PMID- 22652271
TI  - The effect of growth hormone treatment or physical training on motor performance
      in Prader-Willi syndrome: a systematic review.
AB  - Although motor problems in Prader-Willi syndrome (PWS) are prominent in infants,
      and continue into childhood and adulthood, there is little insight into the
      factors important for clinical management. The literature was reviewed to: (1)
      provide an overview of the characteristics and prevalence of motor problems and
      (2) evaluate the effects of growth hormone (GH) treatment and physical training
      on motor performance. A systematic search revealed 34 papers: 13 on motor
      performance; 12 on GH treatment; and nine on physical training. In infants, motor
      development is 30-57% of the normal reference values, and children and adults
      also have significant problems in skill acquisition, muscle force, cardiovascular
      fitness, and activity level. GH treatment positively influenced motor performance
      in infants, children, and adults, although not all studies demonstrated an
      effect. All studies on physical training demonstrated beneficial effects in PWS
      patients. We suggest a combination of GH treatment and physical training to be
      started as soon as possible, especially in infants, to improve motor development
      as this will positively influence general development.

PMID- 22652273
TI  - A novel protein Jpk induces bacterial cell death through reactive oxygen species.
AB  - Jpk, a trans-acting regulatory factor associating with the position-specific
      regulatory element of Hoxa-7, has been reported to induce cell death in both
      prokaryotic and eukaryotic cells upon overexpression. The N- and C-terminal
      deleted variants of Jpk were constructed and then the toxicity of each construct
      was analyzed by checking the viability of the cells and the concomitant
      morphological changes through electron microscopy following the expression. The N
      terminus of Jpk harboring transmembrane domain seemed to be more toxic to
      bacterial cell than C-terminus and the morphology of bacterial cells expressing N
      terminal Jpk was similar to that induced by full length Jpk. The toxicity caused
      by Jpk protein in bacterial cell was through the production of ROS, which was
      decreased by an antioxidant (DTT) in a concentration dependent manner. The
      finding described in this study provides valuable clues on the relationship
      between Jpk toxicity and ROS generation.

PMID- 22652272
TI  - Correlation of methylenetetrahydrofolate reductase polymorphisms with
      homocysteine metabolism in healthy Lebanese adults.
AB  - Hyperhomocysteinemia is associated with several vascular and teratogenic
      conditions. Determinants of total homocysteine concentrations include genetic and
      nutritional factors. This study assesses the relation between homocysteine
      concentrations and MTHFR gene polymorphisms at two common alleles (C677T
      (rs1801133) and A1298C (rs1801131)) as well as other predictors of homocysteine
      (folate, vitamin B(12), body mass index (BMI), age, and gender) in a group of
      healthy Lebanese: 109 males and 124 females aged 17-55years. We used serum for
      the determination of homocysteine, folate and vitamin B(12) levels and blood
      drawn in EDTA tubes for molecular analysis of MTHFR polymorphisms.
      Hyperhomocysteinemia was present in 59/233 (25.3%) of the subjects, with
      male/female ratio of 1.95. Multivariable regression analysis showed that
      homocysteine levels were negatively related to folate and vitamin B(12) and
      positively related to male gender and C677T homozygosity; but not A1298C
      polymorphism, BMI or age. The prevalence of wild, heterozygous, and homozygous
      C677T genotypes was 45.0%, 43.3% and 11.6%, respectively; with a carrier
      frequency of 54.9% and allelic frequency of 33.3%. The A1298C genotypic
      prevalence was 39.5%, 30.9%, and 29.6% respectively; with a carrier frequency of
      60.5% and allelic frequency of 45.1%. C677T/A1289C compound heterozygosity was
      present in 47/233 (20.2%) of volunteers. In this first pilot study, gender,
      folate, vitamin B(12) and C677T mutational status could explain around 32% of
      homocysteine variations. Future larger studies are recommended to investigate
      other predictors of homocysteine variation and combine them with markers explored
      in this and other studies, in order to evaluate their impact on vascular and/or
      congenital diseases.

PMID- 22652274
TI  - The role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes
      mellitus risk: a case-control study in a Turkish population.
AB  - The aim of the present study was to investigate the role of some polymorphisms in
      GSTs (GSTM1, GSTT1 and GSTP1) which are very important protective mechanisms
      against oxidative stress and in OGG1 gene which is important in DNA repair,
      against the risk of type 2 diabetes mellitus (T2DM). 127 T2DM and 127 control
      subjects were included in the study. DNA was extracted from whole blood. Analyses
      of GSTM1 and GSTT1 gene polymorphisms were performed by allele specific PCR and
      those of GSTP1 Ile105Val and OGG1 Ser326Cys by PCR-RFLP. Our data showed that
      GSTM1 null genotype frequency had a 2-6 times statistically significant increase
      in a patient group (OR=3.841, 95% CI=2.280-6.469, p<0.001) but no significance
      with GSTT1 null/positive and GSTP1 Ile105Val genotypes was observed. When T2DM
      patients with OGG1 Ser326Cys polymorphism were compared with patients with a wild
      genotype, a 2-3 times statistically significant increase has been observed (OR
      1.858, 95% CI=1.099-3.141, p=0.021). The combined effect of GSTM1 null and OGG1
      variant genotype frequencies has shown to be statistically significant.
      Similarly, the risk of T2DM was statistically increased with GSTM1 null
      (OR=3.841, 95% CI=2.28-6.469), GSTT1 null+GSTP1 (H+M) (OR=4.118, 95% CI=1.327
      12.778) and GSTM1 null+OGG1 (H+M) (OR=3.322, 95% CI=1.898-5.816) and GSTT1
      null+OGG1 (H+M) (OR=2.179, 95% CI=1.083-4.386) as compared to the control group.
      According to our study results, it has been observed that the combined evaluation
      of GSTM1-GSTT1-GSTP1 and OGG1 Ser326Cys gene polymorphisms can be used as
      candidate genes in the etiology of T2DM, especially in the development of T2DM.

PMID- 22652275
TI  - Genetic polymorphisms in translesion synthesis genes are associated with
      colorectal cancer risk and metastasis in Han Chinese.
AB  - Translesion synthesis (TLS) polymerases have low processivity and fidelity
      compared with replicative polymerases. Defective function of TLS polymerases
      result in chromosome instability. The aim of this study was to evaluate the
      effects of TLS genes on susceptibility and metastasis in colorectal cancer (CRC).
      Four single nucleotide polymorphisms (SNPs) (rs462779, rs11153292, rs373572 and
      rs2233004) of TLS genes were genotyped in the pilot cohort consisted of 516
      patients with CRC and 503 controls, and then replicated in the replication cohort
      of 421 cases and 446 controls. The genotype frequencies of rs462779 and rs373572
      were significantly different between CRC patients and controls in both two
      cohorts, even after it was adjusted by age, gender and smoking status. Stratified
      analysis showed that rs462779 and rs373572 were significantly associated with
      both colon and rectum cancer. In patients with metastatic CRC, the frequency of
      AA genotype of rs373572 was significantly increased as compared with those
      without metastasis CRC (P=0.001). Furthermore, rs462779 and rs373572 exhibited
      remarkably cumulative effect on the risk of CRC (trend P value=0.001). No
      significant difference was observed between other SNPs and CRC. These results
      suggest that polymorphisms in TLS genes are associated with susceptibility to CRC
      in Chinese and might be a novel biomarker for the predication of metastasis risk
      of CRC.

PMID- 22652277
TI  - Self-rated health in diabetes: should the question be the first administered?
AB  - In 599 individuals with Type 2 diabetes, mode of administration of self-rated
      health did not affect ratings when the item was placed before or after health
      related questions. 85% of individuals had stable ratings providing support for
      comparisons across studies using the measure in this population.

PMID- 22652279
TI  - Why does it take so long to process my manuscript?

PMID- 22652278
TI  - [Eosinophilic gastroenteritis].
AB  - PURPOSE: Eosinophilic gastroenteritis is a rare and heterogeneous disorder
      characterized by eosinophilic infiltration of one or more layers of the
      gastrointestinal tract. Although it can involve any part of the gastrointestinal
      tract, the stomach and the proximal small bowel are the most common sites of
      involvement. Clinical features depend on which layer and site are involved. We
      report eight cases of eosinophilic gastroenteritis. METHODS: We conducted a
      retrospective review of consecutive adult cases diagnosed with eosinophilic
      gastroenteritis from 1990 to 2010. The diagnosis was established by histologic
      examination of endoscopic biopsy or operative specimen or by the presence of
      eosinophilic ascites. RESULTS: Eight patients (three men, five women) were
      diagnosed with eosinophilic gastroenteritis during the study period. Three out of
      the eight patients had a history of allergy. All patients had gastrointestinal
      symptoms. The most common symptoms were abdominal pain, vomiting, weight loss and
      ascites. Seven patients (87.5%) had hypereosinophilia. Seven patients had
      involvement of the subserosa and one of the mucosa. Four patients were treated
      with oral prednisolone. The symptoms in all the patients subsided within one
      month. The remaining four patients improved spontaneously. Four of our patients
      were followed-up for at least 2 months (11 to 68 months). A single patient
      presented a relapse. CONCLUSION: Eosinophilic gastroenteritis should be suspected
      in patients having gastrointestinal discomfort along with peripheral
      eosinophilia. Definitive diagnosis requires histological demonstrations of
      eosinophilic infiltration of the gastrointestinal wall or high eosinophilic count
      in ascites fluid.

PMID- 22652280
TI  - Relationship of chronic pain and opioid use with respiratory disturbance during
      sleep.
AB  - This research assessed: 1) whether patients thought to have sleep disordered
      breathing would have more severe symptoms if they were taking opioids; 2) whether
      severity of sleep disordered breathing was associated with class or dose of
      opioid; and 3) whether pain intensity was associated with sleep disordered
      breathing. A descriptive cross-sectional study of patients referred for
      assessment of sleep disorders was conducted. Data were collected on a total of
      419 subjects (no pain [n = 171], chronic pain without opioid treatment [n = 187],
      and chronic pain with opioid treatment [n = 61]). The findings suggest that
      regardless of opioid drug or dose, the management of chronic pain with opioids is
      not likely to exacerbate obstructive sleep apnea at stable doses. However,
      central sleep apnea was associated with opioid use. Patients with chronic pain
      taking opioids had a mean of 5 +/- 13 central apneic events per hour compared
      with 1.6 +/- 7 events per hour in patients without pain and not taking opioids.
      Oxygen saturation mean nadir 83.5% (opioid group) versus 82.9% (no pain, pain
      without opioid) was not significantly different. The clinical relevance of the
      effect is unknown, so the potential for marginal respiratory disturbance (an
      increase of 2.8 central events per hour for every 100 mg morphine-equivalent
      opioid dose) must be weighed against the therapeutic value of pain management
      with opioids.

PMID- 22652276
TI  - A patient-based study on the adherence of physicians to guidelines for the
      management of type 2 diabetes in Turkey.
AB  - AIMS: To evaluate physicians' adherence to guidelines by Diabetes Study Group of
      The Society of Endocrinology and Metabolism of Turkey (SEMT). METHODS: The
      medical records of 1790 patients with type 2 diabetes (mean age, 58.7 +/- 10.9
      years; diabetes duration, 7.7 +/- 7.5 years) followed by 180 physicians during
      last 12 months were reviewed. Adherence to SEMT guidelines was analysed under
      medical history, physical examination and laboratory evaluations subheadings,
      each scored on a 10-point scale. Effects of patients' age, gender, diabetes
      duration, body mass index, chronic complications, physicians' specialty and
      institution on guideline adherence were evaluated. RESULTS: Follow-up procedures
      were >75% compliant for 52% of patients. Full adherence to medical history,
      physical examination and laboratory aspects of SEMT guidelines were met in 68.6%,
      8.3% and 19.2% of patients, respectively. Older patients and males fared better
      for laboratory evaluations. All aspects of guideline adherence were poor in
      patients with short duration of diabetes and in the absence of chronic
      complications. State institutions and family practitioners had lower adherence
      scores for physical examination and laboratory evaluation. CONCLUSIONS: Overall
      guideline adherence of physicians was suboptimal. Educational programs
      emphasizing the preventive aspect of diabetes management, targeted towards family
      practitioners and state institutions, may improve guideline adherence and patient
      outcome.

PMID- 22652281
TI  - Self-treatment of pain among adolescents in an urban community.
AB  - Pain occurrence among adolescents, whether acute or chronic, persistent or
      intermittent, remains high, with potentially serious effects on quality of life,
      physical and emotional functioning, and psychosocial adjustment. The prevalence
      of pain in adolescents varies widely, and although discussed in the literature
      for more than two decades, data on adolescent knowledge and pain self-treatment
      is scarce. This descriptive-correlational study identified pain prevalence and
      intensity and pain self-treatment choices among adolescents in a diverse urban
      community. Almost 90% (n = 253) of high school students reported pain in the
      preceding 2 weeks and completed a series of study questionnaires (demographic
      data form, Brief Pain Inventory-Short Form, Adolescent Self-Treatment Survey).
      Respondents ranged in age from 14 to 19 years (mean 16) and were predominantly
      female (70%) and caucasian (75%). The sample was representative of all high
      school grades, and the majority (86%) reported participation in sports, dance,
      and physical activities. Mean pain scores ranged from 3.0 (current pain) to 6.5
      (worst pain), with significantly higher scores among girls. A gender-related
      effect was also noted for pain interference in activities, mood, and sleep among
      the adolescent girls compared with the boys. Gender also predicted use of self
      treatment methods, with girls more likely to use over-the-counter medications and
      nonpharmacologic therapies. Number of pain sites was also a strong predictor of
      use of self-treatment methods among adolescents. Knowledge of the pain experience
      during adolescence will help guide community-based nursing initiatives aimed at
      increasing awareness, promoting knowledge about pain and its treatment, and
      ensuring safety and positive outcomes related to self-treatment.

PMID- 22652282
TI  - An integrative review of literature examining psychometric properties of
      instruments measuring anxiety or fear in hospitalized children.
AB  - Anxiety and fear are among the most frequently reported emotional responses to
      hospitalization and are known to be contributing factors to pain and other
      negative patient outcomes. The first step in confronting unnecessary anxiety and
      fear is to identify valid and clinically feasible assessment instruments. The
      purpose of this paper is to review and evaluate instruments that measure
      children's fear or anxiety associated with hospitalization or painful procedures.
      A search was conducted of published English-language literature from 1980 through
      2010 with the use of Ovid Health and Psychosocial Instruments, Medline,
      Nursing/Academic Edition, Cinahl, and Google Scholar. Inclusion criteria
      specified that the self-report instrument: 1) was developed in English; 2) was
      developed for and/or widely used with hospitalized children or children
      undergoing medical procedures or treatment; and 3) had research evidence of
      psychometric properties from at least five different studies. A comprehensive
      review of the literature revealed only five fear or anxiety instruments with
      adequate testing for evaluation of reliability and validity. Although all
      instruments have beginning psychometric adequacy, no one tool stands out as
      superior to the others. Therefore, we recommend that researchers and clinicians
      exercise caution in choosing assessment instruments, balancing potential
      strengths with reported limitations. Using more than one tool (triangulating) may
      be one way to achieve more credible results. Knowledge of credible existing
      instruments alerts us to what is possible today and to the imperative for
      research that will improve communication with children tomorrow.

PMID- 22652283
TI  - The role of intravenous acetaminophen in acute pain management: a case
      illustrated review.
AB  - For more than a century, acetaminophen has been recognized worldwide as a safe
      and effective agent for relieving pain and reducing fever in a wide range of
      patients. However, until recently, acetaminophen was available in the United
      States only in oral and rectal suppository formulations. In November 2010, the
      United States Food and Drug Administration granted approval for the use of a new
      intravenous (IV) formulation of acetaminophen for: 1) the management of mild to
      moderate pain; 2) the management of moderate to severe pain with adjunctive
      opioid analgesics; and 3) the reduction of fever in adults and children (age >= 2
      years). This case-illustrated review of IV acetaminophen begins with a discussion
      of the rationale for the drug's development and proceeds to analyze the clinical
      pharmacology, efficacy, safety, and nursing implications of its use, both as
      monotherapy and in combination with other agents as part of a multimodal pain
      therapy strategy.

PMID- 22652284
TI  - Fasciocutaneous flaps of the subscapular artery axis to reconstruct large
      extremity defects.
AB  - INTRODUCTION: The scapular, parascapular and thoracodorsal artery perforator
      (TDAP) flaps represent fasciocutaneous flaps derived from the subscapular artery
      axis. These flaps can be harvested individually or combined as conjoint flaps,
      tailored to reconstruct a wide variety of defects in the extremities. ANALYSIS
      AND METHODS: All patients undergoing free-flap reconstruction at North Bristol
      trust with a fasciocutaneous flap of the subscapular axis from April 2006 until
      April 2010 were included. This cohort of 45 patients was retrospectively
      analysed. The Enneking score for return of limb function was used as an outcome
      measure after reconstruction. Donor-site morbidity analysis was carried out
      prospectively using Oxford Medical Research Council (MRC) score, Vancouver Scar
      Scale and disability of arm, shoulder and hand questionnaire (DASH) scores.
      RESULTS: A total of 45 patients had extremity reconstruction using flaps of the
      subscapular artery axis following severe limb trauma, often comprising open
      tibial fractures. A total of 42 patients had lower limb injuries and three had
      upper limb injuries. All flaps survived. The mean Injury Severity Score (ISS) was
      9.3, the mean Enneking score was 27 at 12 months mean follow-up. In the nine
      conjoint flaps, the mean area of tissue resurfaced was 257 cm2. CONCLUSIONS: In
      this case series of fasciocutaneous flaps of the subscapular artery axis, we
      establish that these flaps are robust and versatile. They replace 'like-with
      like' and have good patient satisfaction. The donor site can be closed primarily,
      is discrete and has minimal donor morbidity. The conjoint flaps can be used for
      reconstruction of very large defects without the need to sacrifice functionally
      important muscle.

PMID- 22652286
TI  - Volume of deep inferior epigastric perforator flap quantified preoperatively by
      using 64-multidetector-row computed tomography.

PMID- 22652285
TI  - Perineal and vaginal wall reconstruction using a combined inferior gluteal and
      pudendal artery perforator flap: a case report.
AB  - Reliable perineal and posterior vaginal wall restoration following extensive
      abdominoperineal excision or pelvic exenteration is a reconstructive challenge,
      especially if the rectus abdominis is unavailable or insufficient for transpelvic
      transposition. In this short report, we present a novel combined perforator-based
      technique, in which an inferior gluteal perforator flap is used for perineal
      reconstruction whereas vaginal reconstruction is performed simultaneously by
      means of a pudendal artery perforator flap. This procedure circumvents functional
      muscle loss, permits a tension-free closure of difficult three-dimensional
      defects and offers a high degree of reconstructive flexibility, which allows a
      straightforward and independent reconstruction of two different anatomical units.

PMID- 22652287
TI  - A subcutaneous pedicled propeller flap: new alternative technique for lower
      eyelid reconstruction after excision of basal cell carcinoma.

PMID- 22652288
TI  - Bilateral Dupuytren's contractures of the thumb interphalangeal joints.
AB  - Dupuytren's disease was first described by Baron Guillaume Dupuytren in 1831. He
      outlined the pathology of palmar fascia thickening and contracture resulting in
      flexion of one or more digits. Dupuytren's disease usually affects the little or
      ring fingers, with the thumb rarely affected. Furthermore, the thumb in isolation
      is only affected in 0.5% of cases, with contracture at the metacarpophalangeal
      joint. We present a unique and interesting case of Dupuytren's disease
      predominantly of the thumbs, with isolated contractures bilaterally at the
      interphalangeal joints, in a 59 year old lady with epilepsy who was otherwise fit
      and well. To our knowledge this disease pattern has never been reported in the
      literature. Furthermore a relevant literature review of Dupuytren's disease
      affecting the thumb, in particular the interphalangeal joint, is presented. Our
      interesting and unique case reinforces the notion that the disease pathogenesis
      is diverse and multifactorial, and provides a further interesting example for the
      literature.

PMID- 22652289
TI  - Smartphone applications for the plastic surgeon: an update of Google's Android
      operating system.

PMID- 22652290
TI  - Legal disputes over informed consent for cosmetic procedures: a descriptive study
      of negligence claims and complaints in Australia.
AB  - BACKGROUND: Plastic surgeons and other doctors who perform cosmetic procedures
      face relatively high risks of malpractice claims and complaints. In particular,
      alleged problems with the consent process abound in this area, but little is
      known about the clinical circumstances of these cases. METHOD: We reviewed 481
      malpractice claims and serious health care complaints resolved in Australia
      between 2002 and 2008 that alleged failures in the informed consent process for
      cosmetic and other procedures. We identified all "cases" involving cosmetic
      procedures and reviewed them in-depth. We calculated their frequency, and
      described the treatments, allegations, and outcomes involved. RESULTS: A total of
      16% (77/481) of the legal disputes over informed consent involved cosmetic
      procedures. In 70% (54/77) of these cases, patients alleged that the doctor
      failed to disclose risks of a particular complication, in 39% patients claimed
      that potential lack of benefit was not explained, and in 26% patients allegations
      centred on the process by which consent was sought. Five treatment types
      liposuction, breast augmentation, face/neck lifts, eye/brow lifts, and
      rhinoplasty/septoplasty-featured in 70% (54/77) of the cases. Scarring (30/77)
      and the need for reoperation (18/77) were among the most prevalent adverse health
      outcomes at issue. CONCLUSION: A mix of factors "supercharges" the informed
      consent process for cosmetic procedures. Doctors who deliver these procedures
      should take special care to canvas the risks and possible outcomes that matter
      most to patients.

PMID- 22652291
TI  - Anomalous large unique muscle belly of flexor digitorum superficialis and the
      absence of palmaris longus in the forearm.
AB  - Anomalies of muscles of the upper extremity are frequently encountered and
      anatomic variations of the flexor digitorum superficialis (FDS) muscle-tendon
      unit are frequently reported by anatomists and clinicians. FDS anomalies can be
      in forms of tendon interconnections, substitution, absence or muscle belly
      variations and most of the times the anomalies of FDS produce few clinical
      symptoms. We report a rare and unusual case of FDS anomaly with a unique and
      large muscle belly. The deformity is type V according to the classification of
      Elliot et al. in which the muscle belly extends to four digits (the index,
      middle, ring and little finger) in the right hand of patient and there is absence
      of the palmaris longus tendon. The hand surgeon should be able to realise all
      variations of the FDS tendon and should be prepared for unexpected findings
      during surgery.

PMID- 22652292
TI  - Re-excision of incompletely excised cutaneous squamous cell carcinoma:
      histological findings influence prognosis.
AB  - INTRODUCTION: We have previously shown 28.6% of re-excisions for margin-positive
      cutaneous SCC to yield residual tumour (positive re-excision). Original tumour
      diameter and thickness conferred significant risks for positive re-excision. We
      now report a 5-year prospective follow-up of our re-excision cohort. RESULTS: Of
      676 consecutive SCC patients, 84 underwent wider-excision for positive margins.
      79 of these patients completed a mean of 28 months follow-up. Overall, 9/79 (11%)
      of this re-excision cohort experienced locoregional recurrence, all within 2
      years of primary resection. Of the positive re-excisions, 29% experienced
      recurrence, vs 5% in those with negative re-excisions. Logistic-regression
      analysis revealed positive re-excision to predict recurrence (P<0.05, RR 10.1),
      independent from tumour-grade, anatomical site, size, and delay to re-excision.
      CONCLUSION: Factors associated with residual tumour on re-excision are similar to
      characteristics of high-risk SCCs; larger tumours in particular are more likely
      to persist and may benefit from wider excision-margins at original resection.
      Positive re-excision is newly identified as a significant risk for locoregional
      recurrence, whilst negative re-excision is associated with a return to a low-risk
      prognosis, for all tumours. Our findings thus support the treatment of cutaneous
      SCC through to completion. We also recommend re-excision where narrow or close
      margins are reported. Patients with a positive re-excision should be considered
      at high risk for recurrence, requiring extended follow-up.

PMID- 22652293
TI  - Prostaglandin E2 promotes the nuclear accumulation of lymphoid enhancer factor-1
      in poorly differentiated breast cancer cells.
AB  - Products of the COX reaction are frequently elevated in solid tumors and their
      roles in the malignant phenotype have been extensively investigated. We have
      shown that COX-2 is essential for the growth of MDA-MB-231 cells in the fat pad
      of SCID mice and for their extrapulmonary colonization following injection in the
      tail vein of SCID mice. The molecular changes that follow shRNA-mediated
      silencing of COX-2 include a significant downregulation of LEF-1, a transcription
      factor normally activated during development following the Wnt-induced nuclear
      translocation of beta-catenin. We also report that COX-2-silenced cells have
      reduced nuclear accumulation of LEF-1 protein and that the COX-2 product PGE(2)
      partially restored nuclear LEF-1 expression in COX-2-silenced cells. Further, we
      demonstrate that, like parental COX-2 containing MDA-MB-231 cells, COX-2-silenced
      cells maintain nuclear localization of beta-catenin.

PMID- 22652294
TI  - Toward a more informative voice range profile: the role of laryngeal vibratory
      mechanisms on vowels dynamic range.
AB  - PURPOSE: The impact that vowels have on the variation across voice range profiles
      (VRPs) is studied along with three factors: fundamental frequency, singer's
      gender, and laryngeal vibratory mechanism used to sing. MATERIALS AND METHODS:
      VRPs of 21 advanced singers were established by recording, in separate takes,
      vocal productions using laryngeal vibratory mechanisms M1 and M2 for /a/, /i/,
      and /o/. Recordings were focused on the range C3-C5, where most singers can sing
      in either M1 or M2. It allows to compare the singer's dynamics in M1 versus M2
      while holding other variables constant. RESULTS: The vowel has an influence on
      the upper limit of singers' VRPs when they use M1 but not when they use M2,
      independently of the singer's gender and the fundamental frequency. DISCUSSION
      AND CONCLUSION: The laryngeal vibratory mechanisms allow one to explain the
      nonconsensual results observed in the literature about the influence of vowels on
      the VRP. A simulation shows that the different influence of vowels on the VRP
      partially results from the different open quotient values that can be observed in
      M1 and in M2.

PMID- 22652296
TI  - [Von Hippel-Lindau disease and the role of the internal medicine physician in
      rare diseases].

PMID- 22652297
TI  - Living with uncertainty.
AB  - The persistence of highly endemic parasitic, bacterial and viral diseases makes
      individuals and populations vulnerable to emerging and re-emerging diseases.
      Evaluating the role of multiple component, often interacting, causes of disease
      may be impossible with research tools designed to isolate single causes.
      Similarly, it may not be possible to identify statistically significant treatment
      effects, even for interventions known to be effective, when multiple morbidities
      are present. Evidence continues to accumulate that nutritional deficiencies,
      bacterial, viral and parasitic coinfections accelerate HIV transmission.
      Inclusion of antiparasitics and other beneficial interventions in HIV-prevention
      protocols is impeded by reliance on inappropriate methodologies. Lack of full
      scientific certainty is not a reason for postponing safe, cost-effective measures
      to prevent irreversible damage.

PMID- 22652295
TI  - Mephedrone ('bath salt') elicits conditioned place preference and dopamine
      sensitive motor activation.
AB  - Abuse of a dangerous street drug called mephedrone (4-methylmethcathinone) has
      become commonplace in the United States. Mephedrone is hypothesized to possess
      abuse liability, share pharmacological properties with psychostimulants, and
      display toxicity that has been linked to fatalities and non-fatal overdoses.
      Knowledge about the pharmacology of mephedrone has been obtained primarily from
      surveys of drug abusers and emergency room visits rather than experimental
      studies. The present study used motor activity and conditioned place preference
      (CPP) assays to investigate behavioral effects of mephedrone. Acute mephedrone
      (3, 5, 10, 30 mg/kg, ip) administration increased ambulatory activity in rats.
      Mephedrone (5 mg/kg, ip)-induced ambulation was inhibited by pretreatment with a
      dopamine D1 receptor antagonist (SCH 23390) (0.5, 1, 2 mg/kg, ip) and enhanced by
      pretreatment with a dopamine D2 receptor antagonist (sulpiride) (2 mg/kg, ip).
      Rats injected for 5 days with low dose mephedrone (0.5 mg/kg, ip) and then
      challenged with mephedrone (0.5 mg/kg, ip) following 10 days of abstinence
      displayed sensitization of ambulatory activity. In CPP experiments, mephedrone
      (30 mg/kg, ip) conditioning elicited a preference shift in both rats and mice.
      The CPP and dopamine-sensitive motor activation produced by mephedrone is
      suggestive of abuse liability and indicates commonalities between the
      neuropharmacological profiles of mephedrone and established drugs of abuse.

PMID- 22652298
TI  - Validity of malaria models: need for a less circular, more secular, argument.

PMID- 22652299
TI  - [Adenoid cystic carcinoma of the head and neck: a retrospective series of 169
      cases].
AB  - PURPOSE: Adenoid cystic carcinoma represents 1% of head and neck cancers. Adenoid
      cystic carcinomas are slow growing tumours with high potential for local
      recurrence. Treatment usually associates radiotherapy and surgery, but the role
      of radiotherapy remains unclear. We report a retrospective multicentric study of
      the management and prognostic factors of 169 adenoid cystic carcinomas of head
      and neck. PATIENTS AND METHODS: Between 1982 and 2010, 169 patients with adenoid
      cystic carcinoma of the head and neck were referred to the Cercle des oncologues
      radiotherapeutes du Sud departments of radiotherapy either for primary untreated
      tumour (n=135) or for a recurrence of previously treated tumour (n=34). The site
      of adenoid cystic carcinoma was: parotid gland (n=48, 28.4%), minor salivary
      gland (n=35, 20.7%), submandibular gland (n=22, 13%), sinus cavities (n=22, 13%),
      other (n=42, 24.9%). Tumour stages were: T1 (12.4%); T2 (14.2%); T3 (12.4%); T4
      (41.4%) and Tx (19.5%). Lymph node involvement was 13% and distant metastasis
      8.9%. For adenoid cystic carcinomas of the parotid gland, major nerve involvement
      was evaluated. Preferential site of metastasis was the lung (87.5%). Treatments
      were: surgery alone (n=27), surgery and adjuvant radiotherapy (n=89), surgery and
      adjuvant chemoradiotherapy (n=12), exclusive chemoradiotherapy (n=13), exclusive
      radiotherapy (n=14), other associations (n=5) and no treatment (n=7).
      Radiotherapy was delivered through photons (n=119), neutrons (n=6), both (n=4).
      Two patients had a brachytherapy boost. Median prescribed doses to T and N were
      respectively 65 Gy and 50 Gy for the 119 photons treated patients. RESULTS: Mean
      follow-up was 58 months (range 1-250 months). As of December 1, 2010, 83 patients
      were alive with no evolutive disease (49%), 35 alive and had recurred, 18 had
      uncontrolled evolutive disease, 28 had died of adenoid cystic carcinoma and 5 of
      intercurrent disease. Overall survival and disease free survival were
      respectively 72% and 72% at 5 years, 53% and 32% at 10 years; 5 and 10-year
      freedom from local recurrence were 81% and 52% respectively. Nerve involvement
      was found in 17/48 parotid gland adenoid cystic carcinomas. The Cox model
      including all patients, showed that surgery (P<0.001), surgical margins
      (P=0.015), nerve involvement (P=0.0079), length of radiotherapy (P=0.018), and
      tumour location (P=0.041) were associated with disease free survival. CONCLUSION:
      In this large series of adenoid cystic carcinoma of head and neck with a majority
      of T3-T4 tumours, 10-year survivals were achieved for 50% of patients.
      Radiotherapy did not impact survival.

PMID- 22652300
TI  - [Stereotactic radiotherapy for intracranial meningioma].
AB  - Meningiomas are the most common non-malignant tumours of the brain. Gross-total
      resection remains the preferred treatment, if achievable without morbidity.
      Radiation therapy is advocated for inoperable, incompletely resected, or
      recurrent grade 1 tumours, if there is a progressive, symptomatic lesion, or in
      case of functional impairment. Postoperative radiation therapy is recommended for
      grade 2 or 3 lesions. Fractionated stereotactic radiotherapy and stereotactic
      radiosurgery are high precision techniques, allowing good sparing of surrounding
      tissues. Fractionated stereotactic radiotherapy and stereotactic radiosurgery
      give comparable results, with excellent 5-year tumour control rates of more than
      90% for benign meningiomas. Toxicity is low and seems equivalent, despite a
      biased use of fractionated stereotactic radiotherapy for larger meningiomas,
      close to critical structures. Fractionated stereotactic radiotherapy seems to be
      of special interest in the treatment of cavernous sinus or optic pathways
      meningiomas. The different therapeutic modalities should be discussed by a
      multidisciplinary team.

PMID- 22652301
TI  - Testing a diathesis-stress model: potential genetic risk factors for development
      of distress in context of acute leukemia diagnosis and transplant.
AB  - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that
      has antidepressant-like effects in animals and may be implicated in the etiology
      of mood-related phenotypes, specifically in the context of stressful life events.
      We hypothesized that this single-nucleotide polymorphism will predict the
      development of psychological distress among patients diagnosed with acute
      leukemia and preparing for hematopoietic stem cell transplant (HSCT). We also
      explored the relationship of other genetic factors to psychological distress,
      including 5HTTLPR and STin2, FKBP5, and the CRHR1 TAT haplotype. METHOD: In a
      retrospective cohort design, 107 adult acute leukemia survivors preparing for
      HSCT at a major medical center completed a pre-HSCT psychological evaluation and
      volunteered to donate blood to the HSCT Cell and Serum Research Repository for
      future research studies. RESULTS: There was evidence of a potential association
      between BDNF (Val66Met) and psychological distress. More specifically, rs6265 was
      related to both personal mental health history (P = 0.09, 0.06 adjusted) and
      diagnosis of depression/adjustment disorder at time of pre-transplant evaluation
      (P = 0.11, 0.09 adjusted). Other genetic factors were unrelated to distress.
      CONCLUSION: The BDNF Val66Met polymorphism may contribute to development of
      depressive symptomatology in patients undergoing stressful life events, such as
      diagnosis of acute leukemia and preparation for HSCT. The SNPs in BDNF might be
      applicable in identifying patients at risk for developing psychological distress
      and depression in the context of coping with stressful medical conditions.
      Polymorphism in other genes (FKBP5, CRHR1, and 5HTT) did not show any significant
      relationships. Replication studies are needed with larger samples of people
      undergoing similar significant life stressors.

PMID- 22652302
TI  - Self-mutilation and biblical delusions: a review.
AB  - OBJECTIVE: To review the literature for cases of deliberate self-harm that
      directly reference Bible verses as a motivation for action and discuss predictive
      factors of such behaviors and post-injury management strategies. METHODS: Sixteen
      cases of self-mutilation prompted by Biblical verses were found in the existing
      literature. The authors also describe a novel case of penile amputation prompted
      by a verse from the Gospel of Matthew. RESULTS: Four biblical verses associated
      with self-mutilation were found, all from the Gospel of Matthew. All patients
      presented with a diagnosis of psychosis at the time of the event. Other common
      themes include substance abuse, guilt over sexual acts, absence of pain or
      regret, and destruction of the severed body part. CONCLUSIONS: Patients with
      symptoms of psychosis may misinterpret various verses from the Gospel of Matthew
      as instructions to engage in self-injurious behavior. Psychiatrists should be
      aware of these four verses to understand their significance and potentially
      forestall these behaviors.

PMID- 22652304
TI  - Type 1 diabetes mellitus in mice increases hippocampal D-serine in the acute
      phase after streptozotocin injection.
AB  - Diabetes mellitus (DM) is known to be a risk factor in the development of
      deficits in cognition, learning, and memory. In DM animal models, including the
      streptozotocin (STZ)-induced diabetic rodent model, abnormalities in the
      regulation of several neurotransmitters have been reported. However, the role in
      DM of d-serine, an endogenous co-agonist of glutamatergic N-methyl-d-aspartate
      receptors, remains unknown. Here, we measured the amounts of d-/l-serine and l
      glutamate in the hippocampi of STZ-treated mice using a 2D-HPLC system from acute
      to chronic phases after the induction of DM. STZ treatment significantly
      increased the d-serine level by 23.7% in the hippocampus compared with vehicle
      treatment at 1 week after the injection, whereas it did not affect the levels of
      l-serine. In contrast, l-glutamate levels in the hippocampus were elevated at 3
      days after STZ injection and rather decreased at 1 week after that. Such
      alterations in the amino acids were not evident in the chronic phases. We further
      tested whether the STZ-induced d-serine increase was caused by DM
      pathophysiology. In vivo, subcutaneous insulin implants into STZ-treated mice
      restored the elevated d-serine levels in the hippocampus. An in vitro study using
      primary cultured hippocampal neurons revealed that treatments of STZ did not
      directly affect the level of d-serine secreted in the cultured media. These
      results indicate that DM pathology caused by insulin deficiency triggers
      transient d-serine increase and l-glutamate alteration in the hippocampus. Such
      aberrant regulations of excitatory neurotransmitters may be relevant to the
      formation of DM-related dysfunction of the central nervous system (CNS).

PMID- 22652303
TI  - New onset of bipolar disorder in late life.

PMID- 22652305
TI  - NMDA preconditioning prevents object recognition memory impairment and increases
      brain viability in mice exposed to traumatic brain injury.
AB  - Recent studies have focused on the role of N-methyl-d-aspartate (NMDA) in brain
      injury. The present study is aimed at verifying memory, anxiety/depression
      parameters, and cellular viability in the brain of mice preconditioned with NMDA
      and subjected to the model of mild traumatic brain injury. For this purpose, male
      albino CF-1 mice were pre-treated with NMDA (75 mg/kg) and subjected to brain
      trauma, and after 24h submitted to memory tasks and anxiety and depression-like
      behavioral tests. The memory tests were evaluated at 1.5h, 24h, and 7 days after
      the training. In addition, the cellular viability was evaluated in the cerebral
      cortex and hippocampus 96 h after the trauma. It was observed that the cellular
      viability was reduced in the hippocampus of the mice subjected to trauma and the
      preconditioning with NMDA was able to protect this damage. All mice learnt the
      task in the habituation test, but in the object recognition task the mice
      preconditioned with NMDA were protected against impairment induced by TBI in both
      short and long-term memory. On the other hand, in the step-down inhibitory
      avoidance test, only the mice treated with NMDA showed impairment of long-term
      memory (7 days after training session). The evaluation of anxiety/depression
      behavior showed no changes after TBI. In conclusion, NMDA preconditioning induced
      impairment of the long-term memory; however, it was able to protect against the
      novel recognition memory impairment and increase the cellular survival in the
      hippocampus of mice exposed to traumatic brain injury.

PMID- 22652307
TI  - Temporal assessment of traumatic axonal injury in the rat corpus callosum and
      optic chiasm.
AB  - Impaired axoplasmic transport (IAT) and neurofilament compaction (NFC), two
      common axonal pathology processes involved in traumatic axonal injury (TAI), have
      been well characterized. TAI is found clinically and in animal models in
      brainstem white matter (WM) tracts and in the corpus callosum (CC), optic chiasm
      (Och), and internal capsule. Previous published quantitative studies of the time
      course of TAI expression induced by the Marmarou impact acceleration model have
      been limited to the brainstem. Accordingly, this study assessed the extent of IAT
      and NFC in the CC and Och at 8h, 28 h, 3 days and 7 days after traumatic brain
      injury (TBI) induction by the Marmarou impact acceleration model. IAT peak
      density was observed at 8h in the CC and 28 h in the Och post-TBI. NFC peak
      density was observed at 28 h in both structures. The density of IAT and NFC
      decreased with increasing survival time in both structures. The NFC density time
      profile followed a similar trend in both the Och and CC, whereas the IAT density
      time profile was variable between the Och and CC. Furthermore, a strong linear
      relationship was observed between IAT and NFC in the CC but not in the Och. These
      findings highlight the heterogeneity of TAI as evidenced by variable IAT and NFC
      injury time profiles in each anatomical structure. This variability indicates the
      requirement of multiple markers for a comprehensive TAI evaluation and multiple
      targeted treatments for TAI polypathology within its therapeutic window time
      frame.

PMID- 22652306
TI  - Contrasting visual working memory for verbal and non-verbal material with
      multivariate analysis of fMRI.
AB  - We performed a Delayed-Item-Recognition task to investigate the neural substrates
      of non-verbal visual working memory with event-related fMRI ('Shape task'). 25
      young subjects (mean age: 24.0 years; STD=3.8 years) were instructed to study a
      list of either 1, 2 or 3 unnamable nonsense line drawings for 3s ('stimulus
      phase' or STIM). Subsequently, the screen went blank for 7s ('retention phase' or
      RET), and then displayed a probe stimulus for 3s in which subjects indicated with
      a differential button press whether the probe was contained in the studied shape
      array or not ('probe phase' or PROBE). Ordinal Trend Canonical Variates Analysis
      (Habeck et al., 2005a) was performed to identify spatial covariance patterns that
      showed a monotonic increase in expression with memory load during all task
      phases. Reliable load-related patterns were identified in the stimulus and
      retention phase (p<0.01), while no significant pattern could be discerned during
      the probe phase. Spatial covariance patterns that were obtained from an earlier
      version of this task (Habeck et al., 2005b) using 1, 3, or 6 letters ('Letter
      task') were also prospectively applied to their corresponding task phases in the
      current non-verbal task version. Interestingly, subject expression of covariance
      patterns from both verbal and non-verbal retention phases correlated positively
      in the non-verbal task for all memory loads (p<0.0001). Both patterns also
      involved similar frontoparietal brain regions that were increasing in activity
      with memory load, and mediofrontal and temporal regions that were decreasing.
      Mean subject expression of both patterns across memory load during retention also
      correlated positively with recognition accuracy (d(L)) in the Shape task
      (p<0.005). These findings point to similarities in the neural substrates of
      verbal and non-verbal rehearsal processes. Encoding processes, on the other hand,
      are critically dependent on the to-be-remembered material, and seem to
      necessitate material-specific neural substrates.

PMID- 22652308
TI  - Delivering post-abortion care through a community-based reproductive health
      volunteer programme in Pakistan.
AB  - This qualitative study was conducted in May-June 2010 with women using post
      abortion care (PAC) services provided by the Marie Stopes Society in Pakistan
      during the six month period preceding the study, more than 70% of whom had been
      referred to the clinics by reproductive health volunteers (RHVs). The aim of the
      study was to establish the socio-demographic profile of clients, determine their
      preferred method of treatment, explore their perceptions of the barriers to
      accessing post-abortion services and to understand the challenges faced by RHVs.
      The sample women were selected from six randomly selected districts of Sindh and
      Punjab. Eight focus group discussions were conducted with PAC clients and fifteen
      in-depth interviews with RHVs. In addition, a quantitative exit interview
      questionnaire was administered to 76 clients. Medical, rather than surgical,
      treatment for incomplete and unsafe abortions was preferred because it was
      perceived to 'cause less pain', was 'easy to employ' and 'having fewer
      complications'. Household economics influence women's decision-making on seeking
      post-abortion care. Other restraining factors include objection by husbands and
      in-laws, restrictions on female mobility, the views of religious clerics and a
      lack of transport. The involvement of all stakeholders could secure social
      approval and acceptance of the provision of safe post-abortion care services in
      Pakistan, and improve the quality of family planning services to the women who
      want to space their pregnancies.

PMID- 22652309
TI  - Electroconvulsive therapy training: can it be a model of an entrustable
      professional activity in a competency program?
AB  - OBJECTIVES: This paper gives an overview of the teaching and assessment process
      in electroconvulsive therapy (ECT) provided in the Hunter Region to see if it can
      be used as a successful example of competency assessment and training. We
      describe the process and practice of training and credentialing in ECT in the
      Hunter Region, and compare these with the requirements of an Entrustable
      Professional Activity (EPA) in particular and competency based training and
      assessment in general. CONCLUSION: The intensely supervised 'hands on' training
      and assessment in this program, and the entrusting of successful graduates to
      perform ECT and related activities with sufficient independence, demonstrate an
      'Entrustable Professional Activity' as proposed for introduction in the Royal
      Australian and New Zealand College of Psychiatrists Competency Based Fellowship
      Program.

PMID- 22652310
TI  - Review of the off-label use of recombinant activated factor VII in pediatric
      cardiac surgery patients.
AB  - In recent years the off-label use of recombinant activated factor VII (rFVIIa)
      has markedly increased, particularly in pediatric cardiac surgery patients, and
      practitioners differ widely in their usage of the drug. In 2009, the Congenital
      Cardiac Anesthesia Society (CCAS) assembled a task force to review the literature
      on rFVIIa administration to pediatric cardiac surgery patients. The goal of the
      CCAS Task Force was to assess current practices and make recommendations about
      rFVIIa therapy to enhance quality of care, improve patient outcomes, reduce
      costs, and develop future research. In this review we summarized the important
      topics on current administration of rFVIIa to pediatric cardiac surgery patients
      including indications for use, efficacy, safety, dosing, and monitoring. All
      pediatric and pertinent adult literature regarding the administration of rFVIIa
      to cardiac surgical patients and published since 2000 were selected and studied.
      Of the 40 pediatric publications reviewed for this report, only 1 was a
      prospective randomized controlled trial thus making determinations of efficacy
      difficult. There is no substantive evidence to support the efficacy of rFVIIa as
      prophylactic or routine therapy during pediatric cardiac surgery. It may prove
      reasonable as rescue therapy because current observational evidence suggests that
      potential benefits of rFVIIa for this indication might outweigh the risks. Rescue
      therapy is appropriate for bleeding that is massive, potentially life
      threatening, and refractory to conventional therapy. Nevertheless, extreme
      caution is advised when considering the administration of rFVIIa to patients who
      are at risk for thromboembolic complications because rates for clinical and
      subclinical thrombosis secondary to rFVIIa therapy are unknown at this time. This
      review is designed to aid practitioners in deciding when and how to administer
      rFVIIa to pediatric cardiac surgery patients; it is not intended to determine
      standard-of-care or practice guidelines. There are insufficient data to make
      evidence-based recommendations. Randomized controlled trials are needed to assess
      the efficacy of rFVIIa as prophylactic, routine, or rescue therapy and to
      determine the drug's safety profile particularly with regard to thrombosis. The
      CCAS rFVIIa Task Force will continue to monitor the literature, gather data, and
      make updates as more information becomes available.

PMID- 22652311
TI  - Trends in in-hospital major morbidity and mortality after total joint
      arthroplasty: United States 1998-2008.
AB  - BACKGROUND: The use of total joint arthroplasties is increasing worldwide. In
      this work we aim to elucidate recent trends in demographics and perioperative
      outcomes of patients undergoing total hip (THA) or total knee arthroplasty (TKA).
      METHODS: Data from the US Nationwide Impatient Sample between 1998 and 2008 were
      gathered for primary THAs and TKAs. Trends in patient age, comorbidity burden,
      length of hospitalization, frequency of major perioperative complications, and in
      hospital mortality were analyzed. In-hospital outcomes were reported as events
      per 1000 inpatient days to account for changes in length of hospitalization over
      time. Deyo index, discharge status, and the interaction effect of time and
      discharge status were included in the adjusted trend analysis for morbidity.
      RESULTS: Between 1998 and 2008, the average age of patients undergoing TKA and
      THA decreased by 2 to 3 years (P < 0.001). The average length of stay decreased
      by approximately 1 day over the time interval studied (P < 0.001). The percentage
      of patients being discharged home declined from 29.7% to 25.4% after TKA and from
      29.3% to 24.2% after THA, in favor of dispositions to long- and short-term care
      facilities (P < 0.0001). Comorbidity burden as measured by the Deyo comorbidity
      index increased by 35% and 30% for TKA and THA patients, respectively (P <
      0.0001). After TKA, there was an increase in the incidence of the following major
      complications: pulmonary embolism (coefficient estimate [CE] 0.069; 95%
      confidence interval [CI], 0.059-0.079; P < 0.0001), sepsis (CE 0.034; 95% CI,
      0.014-0.054; P = 0.001), nonmyocardial infarction cardiac complications (CE
      0.038; 95% CI, 0.035-0.041; P < 0.0001), and pneumonia (CE 0.039; 95% CI, 0.031
      0.047; P < 0.0001). After THA, there was an increase in the incidence of the
      following major complications: pulmonary embolism (CE 0.031; 95% CI, 0.012-0.049;
      P = 0.001), sepsis (CE 0.060; 95% CI, 0.039-0.081; P < 0.0001), nonmyocardial
      infarction cardiac complications (CE 0.040; 95% CI, 0.036-0.043; P < 0.0001), and
      pneumonia (CE 0.039; 95% CI, 0.029-0.048). In-hospital mortality declined after
      both TKA (CE -0.059; 95% CI, -0.077 to -0.040; P < 0.0001) and THA (CE -0.068;
      95% CI, -0.086 to -0.051; P < 0.0001). CONCLUSION: Between 1998 and 2008, trends
      show increases in several major in-hospital complications after THA and TKA,
      including pulmonary embolism, sepsis, nonmyocardial infarction cardiac
      complications, and pneumonia. Despite the increase in complications, declining in
      hospital mortality was noted over this period.

PMID- 22652312
TI  - [French adaptation of a question prompt list for cancer patients and their carers
      in supportive and palliative care].
AB  - Allowing cancer patients to actively participate by asking questions during the
      medical consultation has demonstrated that it improves care provision. In order
      to ease this behaviour, an Australian team developed and validated a question
      prompt list (QPL). Our purpose is to present the French adaptation of this tool.
      Independently translated by three translators, a first version in French was
      submitted to a committee of ten specialists, oncologists and psycho-oncologists.
      We submit that second version to a sample of 10 patients in supportive and
      palliative care unit, including a meeting with a psychologist. Clinicians and
      patients were invited to comment on the clarity, relevance and acceptability of
      the QPL. These findings suggest that French patients assessed this QPL to be
      comprehensive and helpful to express their concerns.

PMID- 22652313
TI  - Too early to call.

PMID- 22652314
TI  - Percutaneous lower extremity arterial interventions using primary balloon
      angioplasty versus cryoplasty: a randomized pilot trial.
AB  - BACKGROUND: Target lesion revascularization (TLR) with primary percutaneous
      transluminal angioplasty (PTA) versus cryoplasty (CRYO) in the treatment of de
      novo femoropopliteal disease has not been well defined in randomized trials.
      METHODS: In this prospective, 2-center randomized trial of PTA vs CRYO of
      femoropopliteal arteries, the primary endpoint of TLR was evaluated at 6 months.
      Secondary endpoints included the rate of bail out stenting because of suboptimal
      acute angiographic results (defined as a residual narrowing of >=30% or type C or
      higher dissection) and target vessel revascularization (TVR). Major adverse
      events including death and amputations were recorded. A two sample t test was
      used to compare the two groups on the continuous variables. For categorical
      variables, cross tabular analysis was conducted with nonparametric tests (Chi
      Square and Fisher's Exact) used to test for significant differences. RESULTS: A
      total of 40 patients were included in the study. Of these 20 patients (24
      vessels) were included in the PTA arm and 20 patients (26 vessels) in the CRYO
      arm. CRYO was performed at a predefined automated pressure of 8 atm. PTA was
      performed at a mean pressure of 9.57+/-1.34 atm (P=.001 compared to CRYO). TLR
      (10.5% vs. 15%, P=NS) and TVR (10% vs 25%, P=NS) were statistically similar
      between the PTA arm compared to the CRYO arm respectively. Bail out stenting was
      performed in 10/24 (41.7%) of vessels in the PTA arm and 10/26 (38.5%) of
      patients in the CRYO arm (P=NS). CONCLUSION: In this pilot randomized study of de
      novo femoropopliteal lesions, CRYO and PTA had the same TLR and TVR at 6 months
      in treating femoropopliteal de novo lesions. Also, bail out stenting was
      statistically similar between the 2 groups. Larger studies are needed to confirm
      these results.

PMID- 22652316
TI  - Symptomatic abnormal vessel wall reaction after implantation of the first
      generation sirolimus-eluting stent: a case series.
AB  - AIMS: Expansive vessel wall remodeling has been previously reported after
      implantation of drug-eluting stents. These abnormal vessel wall reactions (AVWR),
      though uncommon may be associated with serious clinical events. We report on a
      series of patients in whom symptoms developed despite patent stents. METHODS AND
      RESULTS: We report a series of 10 consecutive patients with evidence of AVWR on
      angiography and/or intravascular ultrasonography after implantation of sirolimus
      eluting stents (age 39-90 years, 4 females) during a period of 4 years. All
      patients were symptomatic despite patent stents in coronary angiographies done
      because of persistent chest pain. Four patients subsequently developed very late
      stent thrombosis (VLST). These 4 patients were only on aspirin monotherapy prior
      to the VLST. Of the remaining 6 patients, 3 patients underwent coronary
      interventions (with or without stenting) while the remaining 3 patients were
      managed conservatively. All 6 were advised for life-long dual antiplatelet
      therapy. CONCLUSION: Though uncommon, AVWR might precede VLST. In our series, all
      patients were symptomatic despite patent stents. Additional studies are required
      to identify patients at risk and to determine the best treatment modality for
      this challenging new entity. Until further data become available, these patients
      should stay on dual antiplatelet therapy after an AVWR has been identified.

PMID- 22652318
TI  - V-ATPases in osteoclasts: structure, function and potential inhibitors of bone
      resorption.
AB  - The vacuolar-type H(+)-ATPase (V-ATPase) proton pump is a macromolecular complex
      composed of at least 14 subunits organized into two functional domains, V(1) and
      V(0). The complex is located on the ruffled border plasma membrane of bone
      resorbing osteoclasts, mediating extracellular acidification for bone
      demineralization during bone resorption. Genetic studies from mice to man
      implicate a critical role for V-ATPase subunits in osteoclast-related diseases
      including osteopetrosis and osteoporosis. Thus, the V-ATPase complex is a
      potential molecular target for the development of novel anti-resorptive agents
      useful for the treatment of osteolytic diseases. Here, we review the current
      structure and function of V-ATPase subunits, emphasizing their exquisite roles in
      osteoclastic function. In addition, we compare several distinct classes of V
      ATPase inhibitors with specific inhibitory effects on osteoclasts. Understanding
      the structure-function relationship of the osteoclast V-ATPase may lead to the
      development of osteoclast-specific V-ATPase inhibitors that may serve as
      alternative therapies for the treatment of osteolytic diseases.

PMID- 22652317
TI  - Evaluation of multi-well microelectrode arrays for neurotoxicity screening using
      a chemical training set.
AB  - Microelectrode array (MEA) approaches have been proposed as a tool for detecting
      functional changes in electrically excitable cells, including neurons, exposed to
      drugs, chemicals or particles. However, conventional single well-MEA systems lack
      the throughput necessary for screening large numbers of uncharacterized
      compounds. Recently, multi-well MEA (mwMEA) formats have become available to
      address the need for increased throughput. The current experiments examined the
      effects of a training set of 30 chemicals on spontaneous activity in networks of
      cortical neurons grown on mwMEA plates. Each plate contained 12 wells with 64
      microelectrodes/well, for a total of 768 channels. Of the 30 chemicals evaluated,
      23 were known to alter neuronal function in vivo ("positives"), including 6
      GABAergic and 3 glutamatergic antagonists/agonists, 4 pyrethroids, 3 metals, 2
      cholinesterase inhibitors, 2 nicotinic acetylcholine receptor agonists, valproic
      acid, verapamil, and fluoxetine. Seven compounds expected to have no effect on
      neuronal function were tested as "negatives" (glyphosate, acetaminophen,
      salicylic acid, paraquat, saccharin, d-sorbitol and amoxicillin). Following
      collection of 33 min of baseline activity, chemical effects (50 MUM or highest
      soluble concentration) were recorded for 33 min. Twenty of the positives altered
      the mean network spike rate by more than the 14% threshold (two standard
      deviations from the mean for DMSO control). The three positives without effect
      were bifenthrin, nicotine and imidacloprid. None of the negative compounds caused
      a change in activity beyond the threshold. Based on these results, the mwMEA
      assay has both high sensitivity (87% identification of positive compounds) and
      specificity (100% identification of negative compounds). These experiments
      demonstrate the capacity of mwMEAs to screen compounds for neurotoxic effects
      mediated by a broad variety of mechanisms.

PMID- 22652319
TI  - The role of blood glucose monitoring in non-insulin treated type 2 diabetes: what
      is the evidence?
AB  - Over the past few decades, self-monitoring of blood glucose (SMBG) has been
      recognized as a core component of effective diabetes self-management among
      insulin-treated type 2 diabetes (T2DM) patients. Given the costly nature of
      current T2DM care, especially as the worldwide prevalence of T2DM continues to
      increase rapidly, it is critical to determine whether resources devoted to SMBG
      in non-insulin treated T2DM patients are also justified and being applied
      effectively. We review the conflicting evidence on the use of SMBG in insulin
      naive T2DM patients.

PMID- 22652321
TI  - 4-nitrophenol surface molecularly imprinted polymers based on multiwalled carbon
      nanotubes for the elimination of paraoxon pollution.
AB  - Molecularly imprinted polymers were grafted on the surface of multiwalled carbon
      nanotubes (MWCNT) using the hydrolysis product of paraoxon 4-nitrophenol as
      template, 4-vinyl pyridine (4-VPy) as the functional monomer and divinylbenzen
      (DVB) as the crosslinker. The binding experiments of 4-nitrophenol indicated that
      the MWCNT based molecularly imprinted polymers (MWCNT-MIP) have much higher
      adsorption ability than the MWCNT based non-imprinted polymers (MWCNT-NIP). At
      the same time we found that the adsorption of 4-nitrophenol can help to increase
      the hydrolytic rate of paraoxon, which indicates that there is an obvious
      catalyzing effect on the hydrolysis of paraoxon for this kind of materials.
      Furthermore, the 4-nitrophenol left in the paraoxon hydrolysis medium is only
      0.01056 mM for MWCNT-MIP in the catalytic experiment of paraoxon we made (the
      initial concentration of paraoxon is 0.5 mM and MWCNT-MIP is 4 mg), which
      indicates that this kind of MWCNT based imprinted polymers can not only catalyze
      the hydrolysis of paraoxon but also eliminate the poisonous organism product 4
      nitrophenol.

PMID- 22652320
TI  - High-efficient treatment of wastewater contained the carcinogen naphthylamine by
      electrochemical oxidation with gamma-Al2O3 supported MnO2 and Sb-doped SnO2
      catalyst.
AB  - 1-Naphthylamine wastewater causes severe environmental pollution because of its
      acute toxicity and carcinogenicity in humans, which makes it difficult to reuse
      by conventional technologies. In this study, we report an investigation of the
      electrochemical catalytic oxidation of 1-naphthylamine in synthetic wastewater in
      a 150 mL electrolytic batch reactor with Ti/Sb-SnO(2)/PbO(2) as anode and steel
      plate as cathode, where the reaction was assisted by MnO(2) and Sn(1-x)Sb(x)O(2)
      composite materials as the catalyst and gamma-Al(2)O(3) as the carrier (MnO(2)
      Sn(1-x)Sb(x)O(2)/gamma-Al(2)O(3)). The catalyst was synthesized by impregnating
      process and was characterized by X-ray diffraction (XRD) and X-ray photoelectron
      spectroscopy (XPS). The effects of pH and current density on the efficiency of
      the electrochemical degradation process were also studied. It was found that
      MnO(2)-Sn(1-x)Sb(x)O(2)/gamma-Al(2)O(3) exhibited excellent catalytic activity in
      the electrochemical degradation of 1-naphthylamine wastewater. The results showed
      that the refractory organics in wastewater can be effectively removed by this
      process, and a chemical oxygen demand (COD) removal efficiency of 92.2% was
      obtained in 20 min at pH 7.0 and current density was equal to 50 mA cm(-2).
      According to the experimental results, a hypothetical mechanism of
      electrochemical catalytic degradation was also proposed.

PMID- 22652322
TI  - Quantitative evaluation of multi-walled carbon nanotube uptake in wheat and
      rapeseed.
AB  - Environmental contamination with carbon nanotubes would lead to plant exposure
      and particularly exposure of agricultural crops. The only quantitative exposure
      data available to date which can be used for risk assessment comes from computer
      modeling. The aim of this study was to provide quantitative data relative to
      multi-walled carbon nanotube (MWCNT) uptake and distribution in agricultural
      crops, and to correlate accumulation data with impact on plant development and
      physiology. Roots of wheat and rapeseed were exposed in hydroponics to uniformly
      (14)C-radiolabeled MWCNTs. Radioimaging, transmission electron microscopy and
      raman spectroscopy were used to identify CNT distribution. Radioactivity counting
      made it possible absolute quantification of CNT accumulation in plant leaves.
      Impact of CNTs on seed germination, root elongation, plant biomass,
      evapotranspiration, chlorophyll, thiobarbituric acid reactive species and
      H(2)O(2) contents was evaluated. We demonstrate that less than 0.0050/00 of the
      applied MWCNT dose is taken up by plant roots and translocated to the leaves.
      This accumulation does not impact plant development and physiology. In addition,
      it does not induce any modifications in photosynthetic activity nor cause
      oxidative stress in plant leaves. Our results suggest that if environmental
      contamination occurs and MWCNTs are in the same physico-chemical state than the
      ones used in the present article, MWCNT transfer to the food chain via food crops
      would be very low.

PMID- 22652323
TI  - Arsenic undergoes significant speciation changes upon incubation of contaminated
      rice with human colon micro biota.
AB  - Cellular and animal studies involving MMA(III) (monomethyl arsonous acid) and
      DMA(III) (dimethyl arsinous acid) have indicated that their toxicities meet or
      exceed that of iAs. Thiolated arsenic metabolites were observed in urine after
      oral exposure of inorganic arsenic in some studies. For these species, the
      toxicological profile was not yet fully characterized in human cells. Some
      studies revealed that trivalent organoarsenic species are well absorbed in the
      intestine compared to iAs. However, other studies also indicated that a
      significant amount of rice-bound As reaches the colon, which may be attributed to
      the fibre-rich nature of the rice. Studies have revealed that microorganisms from
      the gut environment are important contributors to arsenic speciation changes. We
      aimed to study how the gut microbial metabolism affects As in different rice
      matrices. This was done in vitro using colon suspension from the Simulator of the
      Human Intestinal Microbial Ecosystem (SHIME system). Significant amounts of
      MMA(III), DMA(III) and MMMTA(V) were formed due to microbial metabolic processes
      like methylation and thiolation. These results suggested that presystemic
      metabolism by human gut micro biota should not be neglected in risk assessment
      studies. In this context, also toxicity and absorption of thiolated species by
      mammalian cells should be further investigated. 

PMID- 22652324
TI  - An exploratory study: student nurses' perceptions of professionalism.
AB  - AIM OF THE STUDY: To explore final year nursing students' perceptions of
      professionalism using a reflective approach. DESIGN: A phenomenological approach
      informed the study, and data was collected by a focus group and five individual
      semi-structured interviews. SUBJECTS: Participants were ten final year student
      nurses studying on the adult nursing education programme in the United Kingdom.
      DATA ANALYSIS: Thematic analysis resulted in an extensive list of general
      statements or 'units of meaning', from which meaningful categories describing a
      phenomenon evolved. RESULTS: The findings revealed that student nurse's perceived
      vulnerability, symbolic representation, role modelling, discontent and
      professional development as elements that informed their own professionalism.
      Additionally, being able to observe the behaviours of registered nurses appeared
      to be significant to the student in the development of their own sense of
      professional identity, using positive and negative role models constructively.
      CONCLUSIONS: It appears that final year student nurses are cognisant of the
      impact of practice scenarios and observational influences, affecting their own
      perceptions of professionalism. They are able to clearly identify and make sense
      of experiences in practice, and constructively use this knowledge to positively
      inform their practice.

PMID- 22652325
TI  - The 'follow-through' experience in three-year Bachelor of Midwifery programs in
      Australia: a survey of students.
AB  - INTRODUCTION: The follow-through experience in Australian midwifery education is
      a strategy that requires midwifery students to 'follow' a number of women through
      pregnancy, labour and birth and into the parenting period. BACKGROUND: The
      experience was introduced by the Australian College of Midwives as part of
      national standards for the three-year Bachelor of Midwifery programs.
      Anecdotally, the introduction caused considerable debate. A criticism was that
      these experiences were incorporated with little evidence of their value. METHODS:
      An online survey was undertaken to explore the follow-through experience from the
      perspectives of current and former students. There were 101 respondents, 93
      current students with eight recent graduates. RESULTS: Participants were positive
      about developing relationships with women. They also identified aspects of the
      follow-through experience that were challenging. Support to assist with the
      experience was often lacking and the documentation required varied. Despite these
      difficulties, 75% felt it should be mandatory as it facilitated positive learning
      experiences. DISCUSSION: The follow-through experience ensured that students were
      exposed to midwifery continuity of care. The development of relationships with
      women was an important aspect of learning. CONCLUSION: Despite these challenges,
      there were significant learning opportunities. Future work and research needs to
      ensure than an integrated approach is taken to enhance learning.

PMID- 22652326
TI  - Mechanistic evaluation of the insulin response in H4IIE hepatoma cells: new
      endpoints for toxicity testing?
AB  - This study was designed to evaluate if the rat H4IIE hepatoma cell line is a
      physiologically relevant model to study hepatic insulin responses to hint at its
      prospective application in pollutant-related insulin resistance research. DNA
      microarray analysis, real-time PCR and flow cytometric cell cycle analysis were
      used to assess the relevance of the insulin response in H4IIE cells. Insulin dose
      dependently stimulated H4IIE growth and time dependently altered the expression
      of the known insulin responsive genes: Fasn, Pck1 and Irs2. Microarray analysis
      performed on cells exposed to insulin (100nM) for 6h and 24h showed that genes
      related to carbohydrate and lipid metabolism were most profoundly afflicted, in
      accordance with in vivo hepatic insulin action. Since changes in carbohydrate and
      lipid metabolism are pivotal in the pathogenesis of insulin resistance, the
      presence of a physiological relevant insulin response in H4IIE cells pleads for
      further testing of its potential use in research on pollutant-driven insulin
      resistance.

PMID- 22652327
TI  - Managing the stiff hand: dual orthosis innovation.

PMID- 22652328
TI  - New clinical motor test for cubital tunnel syndrome.
AB  - When suspecting proximal injury to the ulnar nerve, it is common to assess the
      integrity of the small finger flexor digitorum profundus muscle via methods such
      as isolated blocking exercises, active exercises, and applied resistance. This
      author describes another method of assessing the integrity of proximal ulnar
      nerve motor function.

PMID- 22652329
TI  - The evidence on ways to improve patient's adherence in hand therapy.

PMID- 22652330
TI  - [Major therapeutic advances in the treatment of metastatic melanoma].
AB  - The treatment of metastatic melanoma is presently in complete revolution. Two
      molecules have recently been authorized for this indication. These treatments
      have a very different mechanism of action compared to previous chemotherapies.
      Vemurafenib is a targeted therapy, which blocks BRAF selectively. This molecule
      induces objective responses in more than 50 % of the patients with V600E mutated
      melanoma and a benefit in terms of overall survival. However, many patients
      relapse after about 6 to 8 months of treatment. Many mechanisms are evoked to
      explain these secondary resistances to therapy. Ipilimumab is an immunotherapy
      that blocks CTLA4, a physiological brake of lymphocyte activation. With
      ipilimumab, the objective responses are less frequent than with vemurafenib but
      are more prolonged over time. Two phases III have demonstrated that ipilimumab
      treatment is effective on the overall survival of patients with metastatic
      melanoma. New combination therapies and additional targeted and immunotherapy
      agents are exciting perspectives that make us more optimistic for the future of
      metastatic melanoma treatment.

PMID- 22652331
TI  - Fluorescence study on aggregated lysozyme and lipid bilayer interactions.
AB  - Fluorescent probes 1,6-diphenyl-1,3,5-hexatriene (DPH), pyrene, 4
      dimethylaminochalcone (DMC) and 4-p-(dimethylaminostyryl)-1-dodecylpyridinium
      (DSP-12) have been utilized to monitor the impact of lysozyme (Lz) oligomers on
      physicochemical properties of phosphatidylcholine/cardiolipin (PC/CL) membranes.
      Analysis of spectral responses of the employed probes revealed the reduction of
      membrane free volume and dehydration of lipid bilayer surface upon incorporation
      of Lz self-assemblies. Hydrophobic interactions were found to control the binding
      of Lz oligomers to the lipid bilayer. Comparison of the effects of Lz monomers,
      oligomers and fibrils showed that soluble oligomeric intermediates exert the most
      destructive influence on membrane properties.

PMID- 22652332
TI  - Addition of UVA-absorber butyl methoxy dibenzoylmethane to topical ketoprofen
      formulation reduces ketoprofen-photoallergic reaction.
AB  - Topical application of ketoprofen (KP) clinically evokes the allergic type of
      photocontact dermatitis. To avoid this adverse reaction, we investigated the
      beneficial effect of each ultraviolet (UV) filter that was included in topical
      ketoprofen formulation. We first tested the inhibitory effects of four UVA
      filters by a modified local lymph node assay following KP application on the
      mouse skin and UVA irradiation on the same site. In this assessment, butyl
      methoxy dibenzoylmethane (BMDBM), when included in KP application, exerted the
      most effective inhibitory effect on stimulation with KP and UVA. We manufactured
      topical patch and gel KP applicants containing BMDBM, which retained KP
      penetration through the skin and KP stability toward UVA. The ability of BMDBM in
      these formulations to inhibit KP photosensitivity was evaluated by a modified
      adjuvant and strip method in guinea pigs, and the photoallergic reactions induced
      by the BMDBM-containing KP applicants were lower than the non-containing ones. It
      is known that KP has a cross-reactivity with benzophenone upon UVA exposure, but
      such a photocross-reactivity of BMDBM with KP was not observed in a mouse ear
      swelling model. The anti-inflammatory effect of the BMDBM-containing KP patch
      applicant was comparable to the non-containing one. These results suggest that
      the addition of BMDBM into KP topical formulations is efficacious for inhibition
      of KP photocontact dermatitis.

PMID- 22652333
TI  - [Evaluation of the efficiency of pharmacological antiemetic prophylaxis in
      different risk groups after general anaesthesia in the surgical population of
      Catalonia].
AB  - OBJECTIVE: To assess the efficiency of pharmacological antiemetic prophylaxis in
      patients subjected to surgery under general anaesthetic in different
      postoperative nausea and vomiting (NVPO) risk groups. MATERIAL AND METHODS: A
      randomised, observational, prospective and multicentre cohort study was
      conducted. The study included 1239 patients from 26 hospitals who were subjected
      to elective surgery under general anaesthesia. The data collected included,
      demographic characteristics, the NVPO risk factors, anaesthetic technique, type
      of surgery, the duration, fluid therapy, antiemetic prophylaxis administered, and
      the incidence of NVPO in the first 24h after surgery. A stratified analysis (low,
      moderate and high risk) was performed with the intention of evaluating the
      relationship between prophylaxis and NVPO using a logistic regression model
      adjusted for propensity score. The number of patients needed to treat (NNT) to
      prevent an NVPO episode was then calculated for each of the strata. RESULTS: The
      incidence of NVPO in the low risk stratum was 21.6% without prophylaxis and 8.6%
      with prophylaxis, 31.3% compared to 17.7% in the moderate risk, and 46.5%
      compared to 32.7% in the high risk group. There was a significant protective
      effect in the three strata (odds ratio between treated and untreated patients)
      and in the NNT (95% CI) was 7 (5-11) in the low risk stratum, 7 (5-13) in that of
      the moderate risk, and 6 (4-16) in the high risk. CONCLUSIONS: The efficiency of
      pharmacological antiemetic prophylaxis in patients subjected to surgery under
      general anaesthesia was similar in all risk groups. Not providing antiemetic
      prophylaxis in low risk patients may not be justified due to the cost
      effectiveness criteria. Future clinical guidelines to improve the quality of
      health care of patients operated on under general anaesthesia should consider the
      advantages of a universal NVPO prophylaxis.

PMID- 22652334
TI  - Assessment of drug-drug interactions caused by metabolism-dependent cytochrome
      P450 inhibition.
AB  - This study was designed to develop methods for detecting metabolism-dependent
      reversible, quasi-irreversible, and irreversible cytochrome P450 (CYP) inhibition
      using pooled human liver microsomes and a liquid chromatography/tandem mass
      spectrometry (LC-MS/MS) system. Metabolism-dependent inhibition (MDI) was
      identified based on IC(50) shifts after pre-incubation of the tested compounds
      with NADPH. To distinguish reversible MDI from mechanism-based inhibition (MBI),
      R-fluoxetine and ticlopidine were used as positive inhibitors for reversible MDI
      and MBI of CYP2C19, respectively. R-fluoxetine and ticlopidine inhibited CYP2C19
      activity, as determined using S-mephenytoin as a substrate, and caused 8.7- and
      2.3-fold IC(50) shifts, respectively, after pre-incubation. Inhibition of CYP2C19
      by R-fluoxetine, but not ticlopidine, was markedly reversed by
      ultracentrifugation, and two or three ultracentrifugations were not more
      effective than one, indicating that ultracentrifugation only once may be
      sufficient to reverse the reversible MDI. To distinguish between quasi
      irreversible and irreversible inhibition, diltiazem and mifepristone were used as
      quasi-irreversible and irreversible inhibitors of CYP3A4, respectively, and
      CYP3A4 activity was measured using midazolam and testosterone as substrates.
      After pre-incubation, CYP3A4 IC(50) shifts caused by diltiazem and mifepristone
      were greater than 2.5- and 3.7-fold, respectively. Incubation with 2mM potassium
      ferricyanide for 10min reversed the MDI of CYP3A4 by diltiazem, but not
      mifepristone. Increases in potassium ferricyanide concentration and incubation
      time reduced the recovery of CYP3A4 activity. The established methods were
      confirmed using three CYP3A4 inhibitors including diltiazem, mifepristone and
      amiodarone (a reversible metabolism-dependent inhibitor). We consider these
      methods to be useful tools for discriminating between reversible MDI and MBI.

PMID- 22652335
TI  - Inhibition of mitochondrial complex I by various non-steroidal anti-inflammatory
      drugs and its protection by quercetin via a coenzyme Q-like action.
AB  - Mitochondrial dysfunction plays a major role in the development of oxidative
      stress and cytotoxicity induced by non-steroidal anti-inflammatory drugs
      (NSAIDs). A major objective of the present study was to investigate whether in
      vitro the NSAIDs, aspirin, indomethacin, diclofenac, piroxicam and ibuprofen,
      which feature different chemical structures, are able to inhibit mitochondrial
      complex I. All NSAIDs were effective inhibitors when added both, directly to
      mitochondria isolated from rat duodenum epithelium (50 MUM) or to Caco-2 cells
      (250 MUM). In the former system, complex I inhibition was concentration-dependent
      and susceptible to competition and reversion by the addition of coenzyme Q (32.5
      520 MUM). Based on reports suggesting a potential gastro-protective activity of
      quercetin, the ability of this flavonoid to protect isolated mitochondria against
      NSAIDs-induced complex I inhibition was evaluated. Low micromolar concentrations
      of quercetin (1-20 MUM) protected against such inhibition, in a concentration
      dependent manner. In the case of aspirin, quercetin (5 MUM) increased the IC50 by
      10-fold. In addition, the present study shows that quercetin (5-10 MUM) can
      behave as a "coenzyme Q-mimetic" molecule, allowing a normal electron flow along
      the whole electron transporting chain (complexes I, II, III and IV). The exposed
      findings reveal that complex I inhibition is a common deleterious effect of
      NSAIDs at the mitochondrial level, and that such effect is, for all tested
      agents, susceptible to be prevented by quercetin. Data provided here supports the
      contention that the protective action of quercetin resides on its, here for first
      time-shown, ability to behave as a coenzyme Q-like molecule.

PMID- 22652336
TI  - Assessment of the Turkish health care system reforms: a stakeholder analysis.
AB  - BACKGROUND: The Turkish health care system has been undergoing a significant
      transformation with the Health Transformation Program (HTP) since 2003. The HTP's
      overall objective is to improve governance, efficiency, user and provider
      satisfaction, and long-term fiscal sustainability of the health care system in
      Turkey. OBJECTIVES: To systematically evaluate the effects of the HTP Phase I
      reforms on various stakeholders, and to outline strategic options for the
      implementation of the second phase of health transformation in Turkey. METHODS: A
      total of 47 formal structured stakeholder interviews, representing 29 different
      institutions, are conducted between December 2008 and January 2009. Five main
      components of the HTP were examined: strengthening of the Ministry of Health
      (MoH) capacity for stewardship, universal health insurance, reorganizing health
      service delivery, human resources development, and national health information
      system. RESULTS AND CONCLUSIONS: There is a general agreement among stakeholders
      that the progress made thus far is the greatest in the national health
      information system and the slowest in strengthening the MoH capacity for
      stewardship. It appears that the HTP has the capacity to deliver cost-effective
      health care services and the implementation progress, so far, is in congruence
      with the overall economic development and growth in Turkey.

PMID- 22652337
TI  - [The intermetacarpal double pinning in the surgical treatment of Bennett fracture
      (report of 24 cases)].
AB  - OBJECTIVES: The interest of this work is to show the benefits of surgical
      treatment of Bennett fractures by intermetacarpal double pinning. PATIENTS AND
      METHODS: It is a retrospective study of 24 cases of Bennett fracture treated by
      intermetacarpal double pinning, between January 2005 and December 2009. The
      treatment was surgical for all patients. The intermetacarpal double pinning using
      the technique of Iselin has been reserved for fractures with small fragment found
      in the series in 18 cases (72% of operated patients), and by Tubiana in six cases
      (24%). RESULTS: After a mean of 36 months, we could follow only 21 patients, the
      evaluation of results was based on clinical criteria relevant to pain, mobility
      and the pinch grip, and on criteria after radiological analysis of radiographs
      specific trapezo-metacarpal. All fractures were consolidated. Two cases of
      moderate osteoarthritis were observed. Overall, the results were excellent in 15
      patients (71%), good in four patients (19%) and poor in two patients (10%).
      CONCLUSION: Intermetacarpal double pinning is a technique of choice in surgical
      treatment of Bennett fracture. It ensures a good closed reduction and a
      satisfactory functional result.

PMID- 22652339
TI  - Consistency of the auditory evoked response: the presence of aberrant responses
      and their effect on N100 localization.
AB  - The structure and distribution of the sources underlying the generation of evoked
      potentials (EPs) is often very complex. In an effort to improve localization
      accuracy of the auditory N100 (negative response occurring around 100ms
      poststimulus) component, we analyzed 13 datasets of single-trial EPs obtained
      from normal subjects using an iterative independent component analysis procedure
      which allowed us to detect a clear N100 component in each single trial and to
      study gross changes in component morphology across trials. We found that single
      trial N100 amplitude was most often negative in polarity, as expected, but
      occasionally exhibited a marked reversal to become positive. The average N100,
      however, showed the typical negative polarity, in all subjects. Based on this
      observation, we separated the processed single trials in two groups of typical
      and aberrant responses, and from each group, we computed a partial EP that was
      used to localize the underlying intracranial sources. Additionally, we localized
      the classical ensemble average EP. Before processing, the N100 sources were
      identified correctly in the primary auditory cortex in only four datasets, while
      after processing, all 13 datasets yielded correct localizations, and the
      confidence volume of the sources improved by about 80%. Further analysis
      demonstrated that in nine datasets the improvement was mostly due to the typical
      responses, while the aberrant responses had an antagonistic effect. Our results
      suggest that aberrant responses should not be included in source localizations,
      especially when EEG-based brain mapping is intended as a clinical tool.

PMID- 22652338
TI  - The cortisol awakening response predicts major depression: predictive stability
      over a 4-year follow-up and effect of depression history.
AB  - BACKGROUND: The cortisol awakening response (CAR) has been shown to predict major
      depressive episodes (MDEs) over a 1-year period. It is unknown whether this
      effect: (a) is stable over longer periods of time; (b) is independent of
      prospective stressful life events; and (c) differentially predicts first onsets
      or recurrences of MDEs. METHOD: A total of 270 older adolescents (mean age 17.06
      years at cortisol measurement) from the larger prospective Northwestern-UCLA
      Youth Emotion Project completed baseline diagnostic and life stress interviews,
      questionnaires, and a 3-day cortisol sampling protocol measuring the CAR and
      diurnal rhythm, as well as up to four annual follow-up interviews of diagnoses
      and life stress. RESULTS: Non-proportional person-month survival analyses
      revealed that higher levels of the baseline CAR significantly predict MDEs for
      2.5 years following cortisol measurement. However, the strength of prediction of
      depressive episodes significantly decays over time, with the CAR no longer
      significantly predicting MDEs after 2.5 years. Elevations in the CAR did not
      significantly increase vulnerability to prospective major stressful life events.
      They did, however, predict MDE recurrences more strongly than first onsets.
      CONCLUSIONS: These results suggest that a high CAR represents a time-limited risk
      factor for onsets of MDEs, which increases risk for depression independently of
      future major stressful life events. Possible explanations for the stronger effect
      of the CAR for predicting MDE recurrences than first onsets are discussed.

PMID- 22652340
TI  - A microdevice platform for visualizing mitochondrial transport in aligned
      dopaminergic axons.
AB  - Experimental evidence points to the importance of mitochondrial transport defects
      in contributing to major neurodegenerative diseases, such as Parkinson's disease
      (PD). Studies of mitochondrial transport along single axons are difficult with
      traditional dissociated culture systems and the fragility of the midbrain
      dopaminergic cultures precludes their survival in previously developed
      microfluidic devices with an enclosed architecture. Using soft lithography, we
      generated a microdevice from polydimethylsiloxane (PDMS) for the purpose of
      studying the transport of mitochondria along single dopaminergic axons. The
      device comprises two large open culture chambers connected by a parallel array of
      microchannels that achieves fluidic separation of axons from the soma and allows
      the tracking of mitochondrial movement along oriented axons. Dopaminergic neurons
      from midbrain cultures were successfully cultured within the microdevices for up
      to 4 weeks and extended their axons across the microchannels. Axonal mitochondria
      within the microchannels were labeled by transduction with a mitochondrial
      targeted DsRed2 lentiviral vector or with the mitochondria-specific dye,
      Mitotracker Deep Red and were visually tracked with conventional confocal
      microscopy. The methodology and device that we have described here will allow
      further study of the role of mitochondrial transport defects play in major
      neurodegenerative diseases.

PMID- 22652341
TI  - Farnesoid X receptor targeting to treat nonalcoholic steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver
      condition evolving in a proportion of patients into nonalcoholic steatohepatitis
      (NASH), an aggressive form of NAFLD associated with increased cardiovascular
      mortality and significant risk of progressive liver disease, including fibrosis,
      cirrhosis and hepatocellular carcinoma. At present, no specific therapies for
      NASH exist. In this review, we examine the evidence supporting activation of the
      farnesoid X receptor (FXR), a nuclear hormone receptor regulated by bile acids
      (BAs), for the treatment of NASH. We also discuss the potential of the semi
      synthetic BA derivative obeticholic acid (OCA), a first-in-class FXR agonist, as
      a safe and effective drug to address this significant unmet medical need.

PMID- 22652342
TI  - Nanotechnology-based combinational drug delivery: an emerging approach for cancer
      therapy.
AB  - Combination therapy for the treatment of cancer is becoming more popular because
      it generates synergistic anticancer effects, reduces individual drug-related
      toxicity and suppresses multi-drug resistance through different mechanisms of
      action. In recent years, nanotechnology-based combination drug delivery to tumor
      tissues has emerged as an effective strategy by overcoming many biological,
      biophysical and biomedical barriers that the body stages against successful
      delivery of anticancer drugs. The sustained, controlled and targeted delivery of
      chemotherapeutic drugs in a combination approach enhanced therapeutic anticancer
      effects with reduced drug-associated side effects. In this article, we have
      reviewed the scope of various nanotechnology-based combination drug delivery
      approaches and also summarized the current perspective and challenges facing the
      successful treatment of cancer.

PMID- 22652343
TI  - Understanding the efficacy variables of an HIV vaccine trial.

PMID- 22652345
TI  - Neurocognitive profile and its association with psychopathology in first-degree
      relatives of patients with schizophrenia. a case-control study.
AB  - BACKGROUND: People with schizophrenia show a broad range of neurocognitive
      deficits, which are considered as core features of the disorder and are thought
      to be partly heritable. Similar deficits, albeit at a lesser degree, have been
      also found in their healthy biological relatives. These deficits, if better
      characterized, might represent underlying vulnerable traits for psychosis.
      METHODS: This case-control study compared neurocognitive functioning of adult
      first-degree relatives of patients with schizophrenia (SCZ-RELs) (n=55) with
      healthy control subjects (n=55) and explored its association with the negative
      symptoms. Subjects in both study and control group were assessed with an
      extensive neurocognitive test battery (Trail Making test, Phonemic Verbal
      fluency, Wisconsin Card Sorting Test, Bushke Fuld Test, Stroop Test, n-Back and
      Digit span) and a set of clinical measures (SANS, GAF and DAS). RESULTS: SCZ-RELs
      were more significantly impaired on executive function tasks (i.e. Wisconsin Card
      Sorting Test and the Phonemic Verbal fluency) and displayed significantly more
      severe negative symptoms and poorer social functioning than control subjects.
      Significant correlations between neurocognitive measures and negative symptoms
      were found in the study group, whereas no significant correlations were detected
      among the controls. DISCUSSION: Subtle executive impairments, associated with
      negative symptoms, are shown to be evident in healthy relatives of patients with
      schizophrenia. These deficits, which reflect subtle dysfunction in concept
      formation, flexibility and mental shifting, may be seen as potential phenotypic
      markers of vulnerability for schizophrenia. This raises the question of
      underlying prefrontal dysfunction as core feature of the disorder.

PMID- 22652344
TI  - Risk behaviour and time as covariates for efficacy of the HIV vaccine regimen
      ALVAC-HIV (vCP1521) and AIDSVAX B/E: a post-hoc analysis of the Thai phase 3
      efficacy trial RV 144.
AB  - BACKGROUND: The Thai phase 3 HIV vaccine trial RV 144 showed modest efficacy of a
      vaccine against HIV acquisition. Baseline variables of age, sex, marital status,
      and risk did not modify vaccine efficacy. We did a post-hoc analysis of the
      trial's data to investigate behavioural risk and efficacy every 6 months after
      vaccination. METHODS: RV 144 was a randomised, multicentre, double-blind, placebo
      controlled efficacy trial testing the combination of the HIV vaccines ALVAC-HIV
      (vCP1521) and AIDSVAX B/E to prevent HIV infection or reduce setpoint viral load.
      Male and female volunteers aged 18-30 years were recruited from the community. In
      this post-hoc analysis of the modified intention-to-treat population (16,395
      participants), HIV risk behaviour was assessed with a self-administered
      questionnaire at the time of initial vaccination in the trial and every 6 months
      thereafter for 3 years. We classified participants' behaviour as low, medium, or
      high risk. Both the acquisition endpoint and the early viral-load endpoint were
      examined for interactions with risk status over time and temporal effects after
      vaccination. Multiple proportional hazards regression models with treatment and
      time-varying risk covariates were analysed. FINDINGS: Risk of acquisition of HIV
      was low in each risk group, but 9187 (58.2%) participants reported higher-risk
      behaviour at least once during the study. Participants classified as high or
      increasing risk at least once during follow-up were compared with those who
      maintained low-risk or medium-risk behaviour as a time-varying covariate, and the
      interaction of risk status and acquisition efficacy was significant (p=0.01),
      with greater benefit in low-risk individuals. Vaccine efficacy seemed to peak
      early--cumulative vaccine efficacy was estimated to be 60.5% (95% CI 22-80)
      through the 12 months after initial vaccination--and declined quickly.
      Vaccination did not seem to affect viral load in either early or late infections.
      INTERPRETATION: Future HIV vaccine trials should recognise potential interactions
      between challenge intensity and risk heterogeneity in both population and
      treatment effects. The regimen tested in the RV 144 phase 3 trial might benefit
      from extended immunisation schedules. FUNDING: US Army Medical Research and
      Materiel Command and Division of AIDS, National Institute of Allergy and
      Infectious Disease, National Institutes of Health.

PMID- 22652346
TI  - The efficacy of a brief psycho-educational intervention to improve awareness of
      cognitive dysfunction in schizophrenia.
AB  - People with schizophrenia have neuro-cognitive deficits that are associated with
      poor functional outcome, yet their awareness of their cognitive deficiencies is
      variable. As new treatments for cognition are developed, it will be important
      that patients are receptive to the need for more therapy. Since insight into
      symptoms has been associated with treatment compliance, it may be of value to
      provide psycho-education to improve understanding about cognition in
      schizophrenia. We report a randomized controlled trial that enrolled 80 subjects
      in either a brief psycho-education intervention about cognition, or a control
      condition. Subjects in the two conditions did not differ at baseline in insight
      or receptiveness to treatment, or on demographic, cognitive, or psychiatric
      variables. Current cognitive impairment of subjects was evidenced by the indice
      of working memory, attention and executive functioning abilities, (X=77.45
      intervention group; 82.50 control condition), that was significantly below both
      the normative mean and estimated average premorbid IQs (X=101.3 intervention
      group; X=104.57 control condition). Multivariate repeated measures ANOVAs
      indicated that subjects who received the psycho-education did not improve insight
      into their cognitive deficits or willingness to engage in treatment for cognitive
      dysfunction. While the failure to find a significant impact of this intervention
      on awareness of cognitive deficit and receptiveness to cognitive treatment raises
      questions about the malleability of insight into neuro-cognitive deficits, the
      intervention was briefer than most reported psycho-education programs and multi
      session formats may prove to be more effective.

PMID- 22652347
TI  - New methods can extend the use of minimal important difference units in meta
      analyses of continuous outcome measures.
AB  - OBJECTIVE: For continuous outcomes measured using instruments with an established
      minimally important difference (MID), pooled estimates can be usefully reported
      in MID units. Approaches suggested thus far omit studies that used instruments
      without an established MID. We describe an approach that addresses this
      limitation. STUDY DESIGN: Using the ratio of MID to standard deviation in the
      trials with an established MID, we imputed the MID for instruments without an
      established MID and pooled across all trials. We applied this approach to two
      meta-analyses. RESULTS: In 20 trials of respiratory rehabilitation, the pooled
      estimate did not differ significantly between trials with an established MID and
      those without an established MID (interaction P=0.23). The same was true for 52
      trials examining amitriptyline vs. other antidepressants (interaction P=0.54). In
      the respiratory example, the addition of trials without an established MID led to
      little change in point estimates or confidence intervals (CIs, more data balanced
      by more heterogeneity in a random effects model). In the antidepressant example,
      the additional trials resulted in an identical point estimate with a narrowing of
      the CI. CONCLUSION: Our method allows estimates of a pooled effect in MID units
      using both trials with and without an established MID.

PMID- 22652348
TI  - Visualizing interaction effects: a proposal for presentation and interpretation.
AB  - OBJECTIVE: Interaction terms are often included in regression models to test
      whether the impact of one variable on the outcome is modified by another
      variable. However, the interpretation of these models is often not clear. We
      propose several graphical presentations and corresponding statistical tests
      alleviating the interpretation of interaction effects. STUDY DESIGN AND SETTING:
      We implemented functions in the statistical program R that can be used on
      interaction terms in linear, logistic, and Cox Proportional Hazards models.
      Survival data were simulated to show the functionalities of our proposed
      graphical visualization methods. RESULTS: The mutual modifying effect of the
      interaction term is grasped by our presented figures and methods: the combined
      effect of both continuous variables is shown by a two-dimensional surface
      mimicking a 3D-Plot. Furthermore, significance regions were calculated for the
      two variables involved in the interaction term, answering the question for which
      values of one variable the effect of the other variable significantly differs
      from zero and vice versa. CONCLUSION: We propose several graphical visualization
      methods to ease the interpretation of interaction effects making arbitrary
      categorizations unnecessary. With these approaches, researchers and clinicians
      are equipped with the necessary information to assess the clinical relevance and
      implications of interaction effects.

PMID- 22652349
TI  - Regarding a case report: rare diseases and bibliometric impact factor.

PMID- 22652350
TI  - The "Lost NNT" can be used to represent uncertainty surrounding number needed to
      treat.
AB  - OBJECTIVES: The uncertainty around number needed to treat (NNT) is often
      represented through a confidence interval (CI). However, it is not clear how the
      CI can help inform treatment decisions. We developed decision-theoretic measures
      of uncertainty for the NNT. STUDY DESIGN AND SETTING: We build our argument on
      the basis that a risk-neutral decision maker should always choose the treatment
      with the highest expected benefit, regardless of uncertainty. From this
      perspective, uncertainty can be seen as a source of "opportunity loss" owing to
      its associated chance of choosing the suboptimal treatment. Motivated from the
      concept of the expected value of perfect information (EVPI) in decision analysis,
      we quantify such opportunity loss and propose novel measures of uncertainty
      around the NNT: the Lost NNT and the Lost Opportunity Index (LOI). RESULTS: The
      Lost NNT is the quantification of the lost opportunity expressed on the same
      scale as the NNT. The LOI is a scale-free measure quantifying the loss in terms
      of the relative efficacy of treatment. We illustrate the method using a sample of
      published NNT values. CONCLUSION: Decision-theoretic concepts have the potential
      to be applied in this context to provide measures of uncertainty that can have
      relevant implications.

PMID- 22652351
TI  - Thurstone scaling revealed systematic health-state valuation differences between
      patients with dementia and proxies.
AB  - BACKGROUND: Conventional techniques to measure health-related quality of life
      (HRQoL) in a single value or index are complex, require abstract reasoning
      skills, and are prone to biases (e.g., adaptation). A possible alternative that
      requires less cognitive demand is Thurstone scaling. The present explorative
      study investigates the feasibility and concurrent validity of using Thurstone
      scaling to elicit health-state values in patients with dementia and their
      proxies. METHODS: The participants in the present study were 145 pairs,
      consisting of community-dwelling persons with dementia and their proxies. We
      administered the prototype of the dementia quality-of-life instrument (DQI), a
      dementia-specific HRQoL index instrument, to both patients and proxies. The
      patient's health state as defined by the DQI was placed randomly among nine other
      DQI health states and these were ranked from best to worst. These rankings were
      used for Thurstone scaling. After ranking, the health states were placed on a
      visual analogue scale (VAS). RESULTS: Thurstone scaling had a completion rate of
      37% for patients and 88% for proxies. Thurstone scaling showed a high
      correspondence with VAS values. In addition, we identified a trend that shows
      that patients value most of the evaluated health states systematically lower than
      proxies. CONCLUSIONS: Thurstone scaling proved to be unfeasible for most
      patients, but feasible for proxies. Its concurrent validity was supported and new
      insights into patient-proxy discrepancies were discovered.

PMID- 22652352
TI  - Attachment of hydrogel microstructures and proteins to glass via thiol-terminated
      silanes.
AB  - Micropatterning strategies often call for attachment of non-fouling biomaterials
      and immobilization of proteins in order to create biosensing surfaces or to
      control cell-surface interactions. Our laboratory has made frequent use of
      hydrogel photolithography - a micropatterning process for immobilizing
      poly(ethylene glycol) (PEG) hydrogel microstructures on glass surfaces. In the
      present study we explored the use of thiolsilane as a coupling layer for both
      covalent anchoring of hydrogel microstructures and covalent immobilization of
      proteins on glass. These new surfaces were compared to acryl-silane
      functionalized glass slides that allowed covalent attachment of gels but only
      physical adsorption of proteins as well as surfaces containing a mixture of both
      functional groups. We observed comparable attachment and retention of hydrogel
      microstructures on acryl and thiol-terminated silanes. Ellipsometry studies
      revealed presence of significantly higher level of proteins on thiol
      functionalized glass. Overall, our studies demonstrate that thiol-silane
      functionalized glass surfaces may be used to create complex micropatterned
      surfaces comprised of covalently attached hydrogels and proteins. This simple and
      effective surface modification strategy will be broadly applicable in cellular
      engineering and biosensing studies employing hydrogel micropatterns.

PMID- 22652353
TI  - Synthesis of silver nanorods using Coscinium fenestratum extracts and its
      cytotoxic activity against Hep-2 cell line.
AB  - Silver nanorod has attracted considerable interest due to its potential
      applications in display technologies, thermoelectric and electronic devices,
      optoelectronic devices and biomedicine. In this study, crystalline silver
      nanorods were successfully prepared from AgNO(3) using Coscinium fenestratum
      extract as a reducing agent. The products were characterized by UV-visible
      spectroscopy, FTIR (Fourier-transform IR) spectroscopy and SEM (scanning electron
      microscopy) analysis. Bundle-like nanostructures were observed by SEM analysis
      and the diameters of the nanorods were found to be in the range of 28.5-68.0 nm.
      The MTT assay results revealed that silver nanorod exhibit significant cytotoxic
      effect on HEp-2 cells.

PMID- 22652354
TI  - Mangrove Streptomyces sp. BDUKAS10 as nanofactory for fabrication of bactericidal
      silver nanoparticles.
AB  - Biosynthesis has led to the development of various biomimetic approaches for the
      fabrication of nanoscale materials. The present study reveals a unique procedure
      for the biosynthesis of bactericidal silver nanoparticles (AgNPs) using a novel
      Streptomyces sp. BDUKAS10, an isolate of mangrove sediment. Aqueous silver
      nitrate (AgNO(3)) solution was treated with cell free supernatant (CFS) of the
      isolate to synthesize bactericidal silver nanoparticles. Initial characterization
      was performed by visual observation for color change to intense brown color. UV
      visible spectrophotometry (UV-vis) for measuring surface plasmon resonance
      indicated a maximum absorption peak at 441 nm. Fourier Transform Infrared
      Spectroscopy (FTIR) analysis provides evidence for proteins as possible reducing,
      and capping agents. Energy dispersive X-ray (EDAX) spectroscopy analysis showed
      elemental silver as major signal. Transmission Electron Microscopy (TEM) study
      indicated spherical silver nanoparticles in the size range of 21-48 nm. Compared
      to the CFS, the biosynthesized AgNPs exemplified superior bactericidal efficacy
      towards the tested bacterial strains. Results from this study suggested that
      Streptomyces sp. BDUKAS10 can be advantageous for the synthesis of AgNPs by
      extracellular method in the view of sustainable and ecofriendly approach.

PMID- 22652355
TI  - Functionalized mesoporous silicon for targeted-drug-delivery.
AB  - The present work concerns a preliminary step in the production of anticancer drug
      loaded porous silicon (PSi) for targeted-drug-delivery applications. A successful
      procedure for the covalent attachment of folic acid, polyethylene glycol (PEG)
      and doxorubicin to hydrophilic mesoporous silicon layers is presented. A
      systematic approach has been followed to obtain the optimal composition of the
      N,N'-dicyclohexylcarbodiimide (DCC)/N-hydroxysuccimide (NHS) in dimethylsulfoxide
      (DMSO) solution for the surface activation process of the undecylenic acid (UD)
      grafted molecules to take place with minimal undesired byproduct formation. The
      effect of reactant concentration and kind of solvent (aqueous or DMSO) on the
      attachment of folic acid to the activated PSi layer has been investigated. The
      covalent attachment of the doxorubicin molecules to the PSi layer functionalized
      with folic acid and PEG is discussed. The drug release kinetics as a function of
      pH has been studied. The functionalized PSi particles show a high cytotoxicity
      compared to the equivalent amount of free drug. Cell toxicity tests show clearly
      that the incorporation of folate molecules increases substantially the toxicity
      of the loaded PSi particles. Accordingly this new functionalized PSi may be
      considered a proper candidate for targeted drug delivery.

PMID- 22652356
TI  - Optimization of perfluoro nano-scale emulsions: the importance of particle size
      for enhanced oxygen transfer in biomedical applications.
AB  - Nano-scale emulsification has long been utilized by the food and cosmetics
      industry to maximize material delivery through increased surface area to volume
      ratios. More recently, these methods have been employed in the area of biomedical
      research to enhance and control the delivery of desired agents, as in
      perfluorocarbon emulsions for oxygen delivery. In this work, we evaluate critical
      factors for the optimization of PFC emulsions for use in cell-based applications.
      Cytotoxicity screening revealed minimal cytotoxicity of components, with the
      exception of one perfluorocarbon utilized for emulsion manufacture,
      perfluorooctylbromide (PFOB), and specific w% limitations of PEG-based
      surfactants utilized. We optimized the manufacture of stable nano-scale emulsions
      via evaluation of: component materials, emulsification time and pressure, and
      resulting particle size and temporal stability. The initial emulsion size was
      greatly dependent upon the emulsion surfactant tested, with pluronics providing
      the smallest size. Temporal stability of the nano-scale emulsions was directly
      related to the perfluorocarbon utilized, with perfluorotributylamine, FC-43,
      providing a highly stable emulsion, while perfluorodecalin, PFD, coalesced over
      time. The oxygen mass transfer, or diffusive permeability, of the resulting
      emulsions was also characterized. Our studies found particle size to be the
      critical factor affecting oxygen mass transfer, as increased micelle size
      resulted in reduced oxygen diffusion. Overall, this work demonstrates the
      importance of accurate characterization of emulsification parameters in order to
      generate stable, reproducible emulsions with the desired bio-delivery properties.

PMID- 22652357
TI  - Electrophoresis of a soft toroid of nonuniform structure.
AB  - The electrophoresis of a nonuniformly structured soft particle is modeled
      theoretically by considering an isolated soft toroid comprising a rigid core and
      a polyelectrolyte layer with exponential segment distribution. The influences of
      the thickness of double layer, and the fixed charge density, the friction
      coefficient, the uniformity, and the thickness of the polyelectrolyte layer on
      the electrophoresis behavior of the toroid are examined. We show that for a
      specified fixed charge density, the electrophoresis mobility of the toroid
      increases with increasing double layer thickness, and the higher that density the
      larger the mobility. The thicker the polyelectrolyte layer and/or more uniform
      the segment distribution of that layer the higher the fixed charge density,
      yielding a larger mobility. The thicker the double layer the more significant is
      the influence of the polyelectrolyte layer structure of a toroid on its mobility.

PMID- 22652358
TI  - Effect of pH on stability and plasmonic properties of cysteine-functionalized
      silver nanoparticle dispersion.
AB  - Citrate-stabilized spherical silver nanoparticles (Ag NPs) with d=8.25+/-1.25 nm
      diameter were prepared and functionalized with L-cysteine (Cys) in aqueous
      dispersion. The nanosilver-cysteine interactions have been investigated by Raman
      and (1)H NMR spectroscopy. The effect of pH on stability of biofunctionalized Ag
      NPs was investigated. The cysteine-capped nanosilver dispersions remain stable at
      higher pH (pH>7), while the degree of aggregation increased as the pH decreased.
      Below pH ~7, the characteristic surface plasmon band of bare silver nanoparticles
      was back-shifted from lambda(measured)(bareAgNP)=391 nm to
      lambda(measured)(1)=387-391 nm, while the presence of a new band at
      lambda(measured)(2)=550-600 nm was also observed depending on pH. Finite element
      method (FEM) was applied to numerically compute the absorption spectra of aqueous
      dispersions containing bare and cysteine-functionalized Ag NPs at different pH.
      Both the dynamic light scattering (DLS) measurements, Zeta potential values and
      the transmission electron microscopic (TEM) images confirmed our supposition.
      Namely, electrostatic interaction arose between the deprotonated carboxylate
      (COO(-)) and protonated amino groups (NH(3)(+)) of the amino acid resulting in
      cross-linking network of the Ag NPs between pH ~3 and 7. If the pH is measurable
      lower than ~3, parallel with the protonation of citrate and L-cysteine molecules
      the connection of the particles via l-cysteine is partly decomposed resulting in
      decrease of second plasmon band intensity.

PMID- 22652359
TI  - Interactions between bovine serum albumin and Langmuir films composed of charged
      and uncharged poly(N-isopropylacrylamide) block copolymers.
AB  - The thermoresponsive poly(N-isopropylacrylamide) (PNIPAAM) and NIPAAM block
      copolymer derivatives are attractive for drug delivery applications as they
      contract reversibly at lower critical solution temperatures (LCST) close to
      physiological conditions. In order to investigate biomaterial-protein
      compatibility, we have studied the interaction between PNIPAAM copolymer films
      spread at the air-water surface and bovine serum albumin (BSA) injected below the
      precompressed polymer films, using the Langmuir technique coupled with Brewster
      angle microscopy (BAM). A PNIPAAM homopolymer was applied together with a number
      of PNIPAAM-based di- and triblock copolymers, to assess effects of e.g., charge
      and hydrophobicity on protein-polymer interactions. The nature and strength of
      protein-polymer interaction was found to be tunable, ranging from complex
      formation (PNIPAAM homopolymer) to mixed monolayers and electrostatic cross
      linking, according to the nature of the co-monomer. Results show that
      intercalation versus adsorption can be controlled through polymer composition.

PMID- 22652360
TI  - Effects of ionic surfactants on the morphology of silver nanoparticles using Paan
      (Piper betel) leaf petiole extract.
AB  - Stable silver nanoparticles were synthesized by the reduction of silver ions with
      a Paan (Piper betel) leaf petiole extract in absence and presence of
      cetyltrimethylammonium bromide (CTAB) and sodium dodecyl sulphate (SDS). The
      reaction process was simple and convenient to handle, and was monitored using
      ultraviolet-visible spectroscopy. Absorbance of Ag-nanoparticles increases with
      the concentrations of Paan leaf extract, acts as reducing, stabilizing and
      capping agents. The polyphenolic groups of petiole extract are responsible to the
      rapid reduction of Ag(+) ions into metallic Ag(0). The results indicated that the
      shape of the spectra, number of peaks and its position strongly depend on the
      concentration of CTAB, which played a shape-controlling role during the formation
      of silver nanoparticles in the solutions, whereas SDS has no significant effect.
      The morphology (spherical, truncated triangular polyhedral plate and some
      irregular nanoparticles) and crystalline phase of the particles were determined
      from transmission electron microscopy (TEM) and selected area electron
      diffraction (SAED).

PMID- 22652361
TI  - Sensitive period in flavor learning: effects of duration of exposure to formula
      flavors on food likes during infancy.
AB  - BACKGROUND & AIMS: Emerging research has revealed the existence of periods in
      which the developing brain has heightened sensitivity to environmental
      influences. We discovered a sensitive period, <4 months of age, when exposure to
      the flavor of extensively hydrolyzed protein hydrolysate formulas (ePHF)
      determines its hedonic tone. This formula has pronounced bitter, sour, and savory
      tastes compared to cow-milk-based formulas (CMF). This study aimed to determine
      the effects of duration of exposure during the sensitive period on a food
      containing an exemplar of the savory flavor. METHODS: Formula-fed infants were
      randomized into four groups at age 0.5 months: one control group fed the CMF for
      8 months, and three groups fed ePHF for 1, 3, or 8 months and CMF otherwise. When
      infants were 8.5 months, their acceptance of a savory and plain broth was
      measured. RESULTS: Infants fed hydrolysate formula for 3 or 8 months, but not 1
      month, showed greater acceptance of the savory broth relative to the plain broth
      (p < 0.01) and consumed it at a faster rate (p = 0.01). CONCLUSIONS: The duration
      of flavor exposure affects infants' earliest responses to foods: a 3-month
      exposure to ePHF shifted the hedonic tone for savory flavor.

PMID- 22652362
TI  - Meta-analysis of B vitamin supplementation on plasma homocysteine, cardiovascular
      and all-cause mortality.
AB  - BACKGROUND & AIMS: Results from randomized controlled trials (RCT) of B vitamin
      supplementation on risk of cardiovascular disease (CVD) were inconclusive. The
      aim of the present study was to systematically review the effects of B vitamin
      supplementation on plasma homocysteine (Hcy), cardiovascular and all-cause
      mortality in RCT. METHODS: RCT publications on the effect of B vitamin
      supplementation on plasma Hcy, cardiovascular and all-cause mortality were
      searched from PubMed and web of science database. Data were independently
      abstracted by 2 investigators using a standardized protocol. The results were
      pooled with a fixed-effects model using Stata software. RESULTS: Data from 19
      studies including 47921 participants were analyzed using a fixed-effects model.
      The overall relative risks with 95% confidence intervals of outcomes for patients
      treated with B vitamin supplementation compared with placebo were 0.98 (0.94
      1.03) for CVD, 0.98 (0.92-1.05) for coronary heart disease (CHD), 0.97 (0.90
      1.05) for myocardial infarction (MI), 0.88 (0.82-0.95) for stroke, and 0.97 (0.91
      1.02) for cardiovascular death, 0.99 (0.95-1.04) for all-cause mortality. Blood
      Hcy levels were decreased in all included RCTs. CONCLUSIONS: B vitamin
      supplementation has a significant protective effect on stroke, but none on the
      risk of CVD, MI, CHD, cardiovascular death, or all-cause mortality.

PMID- 22652363
TI  - CD8-positive mycosis fungoides bullosa.

PMID- 22652365
TI  - Neonatal cholestasis with increased 3beta-monohydroxy-Delta5 bile acids in serum
      and urine: not necessarily primary oxysterol 7alpha hydroxylase deficiency.
AB  - BACKGROUND: Inborn errors of bile acid synthesis are rare genetic disorders that
      can present with cholestatic liver disease. Recently we encountered 3 infants
      with neonatal cholestasis and excessive 3beta-monohydroxy-Delta5-C24 bile acids
      in serum and urine. We investigated whether identification of 3beta-hydroxy-5
      cholestenoic acid and 27-hydroxycholesterol in serum and urine of cholestatic
      patients is necessary for diagnosis of primary oxysterol 7alpha-hydroxylase
      deficiency. METHODS: These 3 patients initially led us to suspected oxysterol
      7alpha-hydroxylase deficiency. However, sequence analysis of genomic DNA resulted
      in diagnosis of 2 patients with oxysterol 7alpha-hydroxylase deficiency and 1
      patient with 3beta-hydroxy-Delta5-C27-steroid dehydrogenase/isomerase deficiency.
      We examined identification of 3beta-hydroxy-5-cholestenoic acid and 27
      hydroxycholesterol by gas chromatography-mass spectrometry after diagnosis.
      RESULTS: Interestingly, we detected a peak for 3beta-hydroxy-5-cholestenoic acid
      in serum and 27-hydroxycholesterol of the neutral sterol in urine from 2 patients
      who were diagnosed with primary oxysterol 7alpha-hydroxylase deficiency.
      CONCLUSION: In evaluating infants with cholestasis and excessive 3beta
      monohydroxy-Delta5-C24 bile acids in infancy, one needs to conduct C24 bile acid
      analysis serially. Results can guide performance and interpretation of genomic
      DNA analysis. Moreover, identification of 3beta-hydroxy-5-cholestenoic acid in
      serum and 27-hydroxycholesterol in urine is highly important for diagnosis of
      oxysterol 7alpha-hydroxylase deficiency as is genomic DNA analysis.

PMID- 22652364
TI  - In vitro measurement of attenuation and nonlinear scattering from echogenic
      liposomes.
AB  - Echogenic liposomes (ELIP) are an excellent candidate for concurrent imaging and
      drug delivery applications. They combine the advantages of liposomes
      biocompatibility and ability to encapsulate both hydrophobic and hydrophilic
      drugs-with strong reflections of ultrasound. The objective of this study is to
      perform a detailed in vitro acoustic characterization - including nonlinear
      scattering that has not been studied before - along with an investigation of the
      primary mechanism of echogenicity. Both components are critical for developing
      viable clinical applications of ELIP. Mannitol, a cryoprotectant, added during
      the preparation of ELIP is commonly believed to be critical in making them
      echogenic. Accordingly, here ELIP prepared with varying amount of mannitol
      concentration are investigated for their pressure dependent linear and non-linear
      scattered responses. The average diameter of these liposomes is measured to be
      125-185nm. But they have a broad size distribution including liposomes with
      diameters over a micro-meter as observed by TEM and AFM. These larger liposomes
      are critical for the overall echogenicity. Attenuation through liposomal solution
      is measured with four different transducers (central frequencies 2.25, 3.5, 5,
      10MHz). Measured attenuation increases linearly with liposome concentration
      indicating absence of acoustic interactions between liposomes. Due to the broad
      size distribution, the attenuation shows a flat response without a distinct peak
      in the range of frequencies (1-12MHz) investigated. A 15-20dB enhancement with
      1.67 MUg/ml of lipids is observed both for the scattered fundamental and the
      second harmonic responses at 3.5MHz excitation frequency and 50-800kPa amplitude.
      It demonstrates the efficacy of ELIP for fundamental as well as harmonic
      ultrasound imaging. The scattered response however does not show any distinct
      subharmonic peak for the acoustic excitation parameters studied. Small amount of
      mannitol proves critical for echogenicity. However, mannitol concentration above
      100mM shows no effect.

PMID- 22652366
TI  - Association of total iron binding capacity with coronary artery disease.
AB  - OBJECTIVE: A case-control study and a meta-analysis were conducted to assess the
      association between total iron binding capacity (TIBC) and coronary artery
      disease (CAD) risk. METHODS: A hospital-based case-control study was conducted
      with 258 CAD cases and 282 healthy controls. Logistic regression was utilized to
      estimate odds ratio (OR) with 95% confidence interval (CI) and adjust potential
      confounders. Dose-response relation was investigated between TIBC and CAD risk by
      dividing TIBC concentration into quartiles. A meta-analysis was performed on the
      standardized mean difference (SMD) as well as OR. RESULTS: In our case-control
      study, TIBC was found associated with decreased CAD risk both in univariate
      (OR=0.981, 95% CI=0.975, 0.986) and multivariate (OR=0.979, 95% CI=0.972, 0.986)
      adjusted logistic regressions. The multivariate-adjusted OR for the highest
      quartile compared with the lowest quartile was 0.087 (95% CI=0.042, 0.181). After
      sensitivity analysis, the meta-analysis on SMD showed that TIBC was associated
      with decreased CAD risk (SMD=-0.211, 95% CI=-0.318, -0.104). The results of
      pooled measure on OR (OR=0.970, 95% CI=0.946, 0.995) were consistent with those
      of SMD analysis. CONCLUSION: A weak association was found between TIBC levels and
      decreased CAD risk, further investigations are necessary to clarify the dose
      response relationship.

PMID- 22652367
TI  - Preliminary investigation of contractile activity of Ricinus communis and Euclea
      divinorum extracts on isolated rabbit uterine strips.
AB  - Ricinus communis and Euclea divinorum of the family Euphorbiaceae and Ebenaceae,
      respectively, are traditionally used by Traditional Birth Attendants (TBAs) in
      Machakos district of Kenya to induce or augment labor, manage protracted labor,
      post-partum hemorrhage and retained after birth. Ethno-pharmacological relevance
      of the study will be the provision of scientific evidence and justification for
      the ethnic use of both plants as oxytocic agents in the initiation of labor,
      treatment of prolonged labor, post-partum hemorrhage and retained placenta.
      MATERIALS AND METHODS: The plants were harvested in the wild, identified and
      voucher specimens preserved. The root bark was processed to powder form, from
      which aqueous and ethanol extracts were obtained. Each of the extracts was
      separately tested on isolated uterine muscle tissue from non-pregnant and
      pregnant rabbits. The effect on contraction frequency (number of contractions per
      second) in the absence or presence of oxytocin was evaluated statistically using
      ANOVA. P values <0.05 were considered significant. RESULTS AND CONCLUSIONS: All
      uteri exhibited a strong initial contraction following exposure to the aqueous
      and ethanol root bark extracts of both plants. After recovery, the resumed
      contraction frequencies varied with the plant extract and exogenous hormone. The
      results show that the extracts of both plants were able to stimulate uterine
      tissue contractility directly and to augment the tissue's response to oxytocin.
      The increase in uterine contractions as a percentage relative to negative
      controls was particularly significant in pregnant rabbit tissues in the presence
      of oxytocin, where increments of up to 245% were observed. Further
      pharmacological studies are however required to determine the active principles,
      possible mechanisms of action, efficacy and safety margins of the plant extracts.

PMID- 22652368
TI  - The effect of implementing a modified early warning scoring (MEWS) system on the
      adequacy of vital sign documentation.
AB  - INTRODUCTION AND OBJECTIVES: Early recognition of deteriorating patients results
      in better patient outcomes. Modified early warning scores (MEWS) attempt to
      identify deteriorating patients early so timely interventions can occur thus
      reducing serious adverse events. We compared frequencies of vital sign recording
      24h post-ICU discharge and 24h preceding unplanned ICU admission before and after
      a new observation chart using MEWS and an associated educational programme was
      implemented into an Australian Tertiary referral hospital in Brisbane. DESIGN:
      Prospective before-and-after intervention study, using a convenience sample of
      ICU patients who have been discharged to the hospital wards, and in patients with
      an unplanned ICU admission, during November 2009 (before implementation; n=69)
      and February 2010 (after implementation; n=70). MAIN OUTCOME MEASURES: Any change
      in a full set or individual vital sign frequency before-and-after the new MEWS
      observation chart and associated education programme was implemented. A full set
      of vital signs included Blood pressure (BP), heart rate (HR), temperature (T
      degrees ), oxygen saturation (SaO2) respiratory rate (RR) and urine output (UO).
      RESULTS: After the MEWS observation chart implementation, we identified a
      statistically significant increase (210%) in overall frequency of full vital sign
      set documentation during the first 24h post-ICU discharge (95% CI 148, 288%, p
      value <0.001). Frequency of all individual vital sign recordings increased after
      the MEWS observation chart was implemented. In particular, T degrees  recordings
      increased by 26% (95% CI 8, 46%, p value=0.003). An increased frequency of full
      vital sign set recordings for unplanned ICU admissions were found (44%, 95% CI 2,
      102%, p value=0.035). The only statistically significant improvement in
      individual vital sign recordings was urine output, demonstrating a 27% increase
      (95% CI 3, 57%, p value=0.029). CONCLUSIONS: The implementation of a new MEWS
      observation chart plus a supporting educational programme was associated with
      statistically significant increases in frequency of combined and individual vital
      sign set recordings during the first 24h post-ICU discharge. There were no
      significant changes to frequency of individual vital sign recordings in unplanned
      admissions to ICU after the MEWS observation chart was implemented, except for
      urine output. Overall increases in the frequency of full vital sign sets were
      seen.

PMID- 22652369
TI  - Diet promotes sleep duration and quality.
AB  - Sleep, much like eating, is an essential part of life. The mechanisms of sleep
      are only partially clear and are the subject of intense research. There is
      increasing evidence showing that sleep has an influence on dietary choices. Both
      cross-sectional and epidemiologic studies have demonstrated that those who sleep
      less are more likely to consume energy-rich foods (such as fats or refined
      carbohydrates), to consume fewer portions of vegetables, and to have more
      irregular meal patterns. In this narrative review, we pose the opposite question:
      can ingested food affect sleep? The purpose of this review is to discuss the
      evidence linking diet and sleep and to determine whether what we eat and what
      kind of nutrients we obtain from the food consumed before bedtime matter. In
      addition, scientific evidence behind traditional sleep-promoting foods such as
      milk and some herbal products is briefly described. These are reviewed using data
      from clinical trials, mostly in healthy subjects. In addition, we discuss the
      possible mechanisms behind these observations. Lastly, we summarize our findings
      that emerging evidence confirms a link between diet and sleep. Overall, foods
      impacting the availability of tryptophan, as well as the synthesis of serotonin
      and melatonin, may be the most helpful in promoting sleep. Although there are
      clear physiological connections behind these effects, the clinical relevance
      needs to be studied further.

PMID- 22652370
TI  - High L-carnitine concentrations do not prevent late diabetic complications in
      type 1 and 2 diabetic patients.
AB  - Increased intake of L-carnitine, a cofactor in cellular energy metabolism, is
      recommended for diabetic patients with late complications. However, its clinical
      benefits remain controversial. We hypothesized that patients with low L-carnitine
      levels would have an increased rate of diabetic complications. To test this
      hypothesis, we evaluated the relationship of L-carnitine concentrations in blood
      with the prevalence and severity of late diabetic complications in type 1 and 2
      diabetic patients. Human blood samples were collected from 93 and 87 patients
      diagnosed as having type 1 or type 2 diabetes, respectively, and 122 nondiabetic
      individuals. The determination of free L-carnitine concentrations in whole blood
      lysates was performed using ultra-performance liquid chromatography with tandem
      mass spectrometry. In diabetic patients, diabetic complications such as
      neuropathy, retinopathy, nephropathy, or hypertension were recorded. The average
      L-carnitine concentration in the blood of control subjects was 33 +/- 8 nmol/mL,
      which was not significantly different from subgroups of patients with type 1 (32
      +/- 10 nmol/mL) or type 2 diabetes (36 +/- 11 nmol/mL). Patients with low (<20
      nmol/mL) l-carnitine levels did not have increased occurrences of late diabetic
      complications. In addition, patient subgroups with higher L-carnitine
      concentrations did not have decreased prevalence of late diabetic complications.
      Our results provide evidence that higher L-carnitine concentrations do not
      prevent late diabetic complications in type 1 and 2 diabetic patients.

PMID- 22652371
TI  - Vitamin E supplementation protects erythrocyte membranes from oxidative stress in
      healthy Chinese middle-aged and elderly people.
AB  - Elderly people are subject to higher levels of oxidative stress than are young
      people. Vitamin E, as a powerful antioxidant residing mainly in biomembranes, may
      provide effective protection against oxidative membrane damage and resultant age
      related deterioration, especially in the elderly. We hypothesized that
      appropriate levels of vitamin E supplementation would protect erythrocyte
      membranes from oxidative stress and thus improve membrane fluidity in healthy
      middle-aged and elderly people. To test this, we conducted a 4-month double
      blind, randomized trial in which 180 healthy subjects (55-70 years old) were
      randomly divided into 4 groups: group C (control), and 3 treatment groups in
      which daily doses of 100 mg (VE1), 200 mg (VE2), and 300 mg (VE3) dl-alpha
      tocopheryl acetate were administered. We measured plasma alpha-tocopherol
      concentration, malondialdehyde, and superoxide dismutase levels, erythrocyte
      hemolysis, and erythrocyte membrane fluidity at the beginning and end of the
      trial. After 4 months supplementation, plasma alpha-tocopherol concentrations in
      the 3 treatment groups had increased by 71%, 78%, and 95%, respectively (all P <
      .01), and significant decreases in plasma malondialdehyde concentrations were
      observed in these groups (all P < .05). Erythrocyte hemolysis was decreased by
      20% to 38% after vitamin E supplementation (all P < .05), and in addition, groups
      VE2 and VE3 showed dramatic improvements in erythrocyte membrane fluidity (P <
      .01). Surprisingly, superoxide dismutase activity also decreased significantly in
      the treatment groups (all P < .05). In summary, vitamin E supplementation
      apparently alleviates oxidative stress in healthy middle-aged to elderly people,
      at least in part by improving erythrocyte membrane fluidity and reducing
      erythrocyte hemolysis.

PMID- 22652372
TI  - Food intake in women two years or more after bariatric surgery meets adequate
      intake requirements.
AB  - Restricted food intake after bariatric surgery can be an important factor both in
      the long-term control of body weight and in the onset of nutritional
      deficiencies. The objective of this study was to assess the adequacy of food
      intake in women two or more years after bariatric surgery according to the excess
      weight lost. A group of 141 women who underwent banded Roux-en-Y gastric bypass
      (RYGB) was divided according to the percentage of excess weight they lost
      (%EWL)<50; 50?75; = 75. The habitual energy and nutrient intakes were determined
      by a 24-hour recall over two days and the probability of adequate intake was
      based on the Dietary Reference Intake. The mean total estimated energy
      requirement (EER) as well as energy, macronutrient and cholesterol intakes did
      not differ among the groups. Only the %EWL<50 group had an intake equal to their
      EER, but they presented a higher number of inadequacies, such as low levels of
      magnesium, folic acid and vitamins C and E. Calcium and dietary fiber intakes
      were extremely low in all three groups. In conclusion, weight loss after surgery
      is associated with food habits that favor energy intake over micronutrient
      intake.

PMID- 22652373
TI  - Association between endothelial nitric oxide gene intron 4a4b VNTR polymorphism
      and plasma homocysteine concentrations in Tunisian male patients with myocardial
      infarction.
AB  - Many studies have shown that hyperhomocysteinemia may be an independent risk
      factor for coronary artery disease. However, not all prospective studies support
      an association between elevated plasma homocysteine levels and coronary artery
      disease. Nitric oxide (NO) plays a relevant role in various events during
      atherogenesis, and in vitro data suggest that NO may modulate total homocysteine
      (tHcy) concentrations, whereas polymorphisms of the endothelial nitric oxide
      (NOS3) gene have been reported to be related to an increased risk of myocardial
      infarction (MI) and hyperhomocysteinemia, but the results have been
      controversial. We hypothesized that the NOS3 synthase 4a4b VNTR polymorphism is a
      determinant of tHcy concentrations and tested this in 310 patients with MI and
      250 controls. The NOS3 gene intron 4a4b VNTR polymorphism was analyzed by
      polymerase chain reaction analysis. There was no significant difference in the
      homocysteine levels between patients with MI and controls. The frequencies of the
      NOS34b4b, 4b4a, and 4a4a genotypes in the MI group were significantly different
      from those in the control group. In patients with MI, plasma tHcy concentrations
      were significantly different among the NOS3 genotypes (13.5+/-4.5, 18.5+/-3.9,
      and 20.4+/-2.1 MUmol/L for 4b4b, 4a4b, and 4a4a genotypes, respectively; P<.001).
      However, no significant difference was observed for tHcy concentrations in the
      control group. In conclusion, the NOS34a4b gene polymorphism (presence of 4a
      allele) is associated with MI and influences plasma tHcy concentrations in
      patients with MI in the Tunisian male population.

PMID- 22652374
TI  - Renoprotective effects of (+)-catechin in streptozotocin-induced diabetic rat
      model.
AB  - Diabetic nephropathy is a complication of diabetes mellitus leading to end-stage
      renal disease. Oxidative stress and inflammation play a major role in the
      pathogenesis of diabetic nephropathy. Green tea, known for its antioxidant and
      anti-inflammatory properties, has been shown to be renoprotective. We
      hypothesized that (+)-catechin (CTN), a component of green tea, is responsible
      for the renoprotection. Our investigation of the therapeutic potential of CTN in
      streptozotocin-induced diabetic rats demonstrated for the first time that the
      effects of CTN treatment were comparable with the effects of an angiotensin
      converting enzyme inhibitor (ACEi) enalapril for the treatment of albumin
      excretion. After 12 weeks of CTN treatment with 35 mg/d in the drinking water,
      urinary albumin excretion and plasma creatinine concentrations in all the
      diabetic treatment groups were reduced, compared with the diabetic group with no
      treatment. Urine creatinine and creatinine clearance were higher in diabetic
      groups treated with CTN and ACEi compared with the diabetic group with no
      treatment. Endothelin 1, lipid peroxidation, concentration of alanine transferase
      enzyme, and expression of fibronectin were lower in all the treatment groups
      compared with the diabetic group with no treatment. Concentrations of free thiols
      were higher in the CTN-treated group compared with the diabetic rats with no
      treatment. Our findings suggest that CTN has renoprotective properties comparable
      with ACEi, and coadministration of CTN and enalapril might be useful in reducing
      albumin excretion as well as improving endothelial function. (+)-Catechin might
      be successfully used in the future for clinical situations where ACEi is poorly
      tolerated or contraindicated.

PMID- 22652375
TI  - Delphinidin-3-O-galactoside protects mouse hepatocytes from (-)-epigallocatechin
      3-gallate-induced cytotoxicity via up-regulation of heme oxygenase-1 and heat
      shock protein 70.
AB  - Delphinidin-3-O-galactoside (D3G) is a water-soluble anthocyanin with antioxidant
      activity. (-)-Epigallocatechin-3-gallate (EGCG) is also known as a powerful
      antioxidant but concomitantly possesses a prooxidative property. We hypothesized
      that D3G is capable of protecting the EGCG-induced cytotoxicity and endoplasmic
      reticulum (ER) stress via inducing self-protective proteins and antioxidant
      enzymes. (-)-Epigallocatechin-3-gallate (200-500 MUM) dose dependently decreased
      the viability of hepa1c1c-7 mouse hepatocytes, whereas D3G (50-500 MUM) did not
      change it. Pretreatment with D3G significantly suppressed EGCG-induced
      cytotoxicity in a time-dependent manner (0, 6, and 24 hours). (-)
      Epigallocatechin-3-gallate drastically decreased heme oxygenase-1 and heat shock
      protein 70 messenger RNA (mRNA) levels, whereas, pretreatment with D3G markedly
      attenuated their down-regulations. Delphinidin-3-O-galactoside remarkably
      decreased EGCG-induced ER stress responses such as C/EBP-homologus protein mRNA
      expression and X-box-binding protein-1 mRNA splicing. Taken together, our data
      suggest that D3G is capable of masking the EGCG-induced cytotoxicity and ER
      stress, presumably through up-regulation of antioxidant enzymes and heat shock
      proteins.

PMID- 22652376
TI  - Platycodon grandiflorum root attenuates vascular endothelial cell injury by
      oxidized low-density lipoprotein and prevents high-fat diet-induced dyslipidemia
      in mice by up-regulating antioxidant proteins.
AB  - We hypothesized that a Platycodon grandiflorum root (PG) ethyl acetate extract
      (PGEA) would help reduce the vascular cell injury caused by oxidized low-density
      lipoprotein (oxLDL) and prevent high-fat (HF) diet-induced dyslipidemia and
      oxidative stress by up-regulating antioxidant proteins. We investigated the
      protective effects of PGEA against vascular endothelial cell injury induced by
      oxLDL and dyslipidemia induced by an HF diet, and the mechanisms underlying these
      effects were studied. The protective effects of PGEA were investigated with
      respect to calf pulmonary arterial endothelial (CPAE) cell viability and the
      lactate dehydrogenase release during oxLDL treatment. The in vivo effects of PGEA
      were examined using C57BL/6 mice, which were fed an HF diet for 9 weeks. The HF
      diet was supplemented with 0, 25, or 75 mg/kg PGEA during the last 4 weeks of the
      experimental period. Histologic analyses of hepatic lipid accumulation were
      performed. The changes in antioxidant protein levels induced by PGEA, which
      protects against HF diet-induced oxidative stress, were measured using a
      proteomics approach. We found that PGEA exhibited antioxidant activity. In CPAE
      cells, PGEA inhibited both oxLDL-induced cell death and lactate dehydrogenase
      release. In the HF diet-induced obese mice that received PGEA, we observed
      significantly reduced plasma and hepatic lipid levels, demonstrating that PGEA
      has beneficial effects on hyperlipidemia. In addition, we found that PGEA caused
      the up-regulation of antioxidant proteins. These findings suggest that the
      antioxidant effects of PGEA may protect against oxidative stress-related
      diseases.

PMID- 22652377
TI  - Sulforaphane retards the growth of UM-UC-3 xenographs, induces apoptosis, and
      reduces survivin in athymic mice.
AB  - Sulforaphane (SFN), an isothiocyanate that exists exclusively in cruciferous
      vegetables, may be the most promising preventive agent for bladder cancer (BC) to
      date. We previously observed that SFN dramatically inhibits human BC T24 cells in
      vitro. Our hypothesis is that SFN may attenuate BC growth. To test our
      hypothesis, we investigated the effect of SFN on human BC UM-UC-3 cell xenografts
      implanted into athymic mice. Sulforaphane extract was routinely prepared in our
      laboratory, and its content was measured with high-performance liquid
      chromatography. Athymic mice were injected subcutaneously with a UM-UC-3 cell
      suspension (2.0*10(6) cells/200 MUL per mouse) and randomly divided into 2
      groups. The positive control group was orally gavaged with water, and the
      treatment group was orally administered SFN from broccoli sprout (12 mg/kg body
      weight) for 5 weeks. At the end of the experiment, tumor tissues were harvested
      and processed for hematoxylin and eosin staining and immunohistochemistry. The
      average tumor volume decreased from 4.1+/-1.67 cm(3) in the positive control mice
      to 1.5+/-0.72 cm(3) in the SFN-treated mice, evidencing an inhibitory rate of
      63%. The SFN extract also reduced the appearance of tumors, including
      karyopyknosis and angiogenesis. Sulforaphane extract induced caspase 3 and
      cytochrome c expression but reduced the expression of survivin. Sulforaphane
      extract retards the growth of UM-UC-3 xenografts in vivo, confirming its future
      potential in BC therapy.

PMID- 22652378
TI  - Fish oil supplementation maintains adequate plasma arachidonate in cats, but
      similar amounts of vegetable oils lead to dietary arachidonate deficiency from
      nutrient dilution.
AB  - Because fatty acid (FA) metabolism of cats is unique, effects of dietary fish and
      vegetable oil supplementation on plasma lipids, lipoproteins,
      lecithin/cholesterol acyl transferase activities, and plasma phospholipid and
      esterified cholesterol (EC) FAs were investigated. Cats were fed a commercial
      diet supplemented with 8 g oil/100 g diet for 4 weeks using either high-oleic
      acid sunflower oil (diet H), Menhaden fish oil (diet M), or safflower oil (diet
      S). When supplemented, diet M contained sufficient arachidonate (AA), but diets H
      and S were deficient. We hypothesized that diet M would modify plasma lipid
      metabolism, increase FA long-chain n-3 (LCn-3) FA content but not deplete AA
      levels. Also, diet S would show linoleic acid (LA) accumulation without
      conversion to AA, and both vegetable oil supplements would dilute dietary AA
      content when fed to meet cats' energy needs. Plasma samples on weeks 0, 2, and 4
      showed no alterations in total cholesterol or nonesterified FA concentrations.
      Unesterified cholesterol decreased and EC increased in all groups, whereas
      lecithin/cholesterol acyl transferase activities were unchanged. Diet M showed
      significant triacylglycerol lowering and decreased pre-beta-lipoprotein
      cholesterol. Plasma phospholipid FA profiles revealed significant enrichment of
      18:1n-9 with diet H, LA and 20:2n-6 with diet S, and FA LCn-3FA with diet M.
      Depletion of AA was observed with diets H and S but not with diet M. Diet M EC FA
      profiles revealed specificities for LA and 20:5n-3 but not 22:5n-3 or 22:6n-3.
      Oversupplementation of some commercial diets with vegetable oils causes AA
      depletion in young cats due to dietary dilution. Findings are consistent with the
      current recommendations for at least 0.2 g AA/kg diet and that fish oil
      supplements provide both preformed LCn-3 polyunsaturated FA and AA.

PMID- 22652379
TI  - Tomato paste supplementation improves endothelial dynamics and reduces plasma
      total oxidative status in healthy subjects.
AB  - Consumption of tomato products is linked to beneficial outcomes through
      antioxidant and anti-inflammatory mechanisms. The aim of this study was to
      determine whether a 14-day period of tomato paste supplementation would improve
      endothelial function. Nineteen volunteers (mean age, 39 +/- 13 years; 8 men/11
      women) were studied in a randomized (exposure sequence), single-blind (operator),
      crossover design. The study consisted of a supplementation arm (70 g tomato paste
      containing 33.3 mg of lycopene) and a control arm, during which no tomato paste
      was added to their regular diet. Volunteers maintained their regular diet during
      study arms. Two-week washout periods preceded each arm. Flow-mediated dilatation
      (FMD) measured by brachial artery ultrasonography was used as an estimate of
      endothelial function at day 1 (acute response) and day 15 (midterm response).
      Plasma lipid peroxides were measured with a photometric enzyme-linked
      immunosorbent assay as an index of total oxidative status. Tomato supplementation
      led to an overall FMD increase compared with the control period (P = .047 for
      repeated-measures 3 * 2 analysis of variance). At day 1, FMD was not
      significantly increased (P = .329). By day 15, tomato supplementation resulted in
      an increase in FMD by 3.3% +/- 1.4%, whereas at the control arm, FMD declined by 
      0.5% +/- 0.6% (P = .03); magnitudes of change are absolute FMD values. Total
      oxidative status decreased at the end of the supplementation period compared with
      baseline values (P = .038). Daily tomato paste consumption exerts a beneficial
      midterm but not short-term effect on endothelial function. Further studies are
      warranted to explore the effects of tomato paste on endothelial dilation in
      different age groups and comorbidities.

PMID- 22652380
TI  - Adherence of platelets to in situ albumin-binding surfaces under flow conditions:
      role of surface-adsorbed albumin.
AB  - Surfaces that preferentially bind human serum albumin (HSA) were generated by
      grafting albumin-binding linear peptide (LP1) onto silicon surfaces. The research
      aim was to evaluate the adsorption pattern of proteins and the adhesion of
      platelets from platelet-poor plasma and platelet-rich plasma, respectively, by
      albumin-binding surfaces under physiological shear rate (96 and 319 s(-1))
      conditions. Bound proteins were quantified using enzyme-linked immunosorbent
      assays (ELISAs) and two-dimensional gel electrophoresis. A ratio of ~1000:100:1
      of adsorbed HSA, human immunoglobulin (HIgG) and human fibrinogen (HFib) was
      noted, respectively, on LP1-functionalized surfaces, and a ratio of ~5:2:1 of the
      same was noted on control surfaces, as confirmed by ELISAs. The surface-adsorbed
      von Willebrand factor was undetectable by sensitive ELISAs. The amount of adhered
      platelets correlated with the ratio of adsorbed HSA/HFib. Platelet morphology was
      more rounded on LP1-functionalized surfaces when compared to control surfaces.
      The platelet adhesion response on albumin-binding surfaces can be explained by
      the reduction in the co-adsorption of other plasma proteins in a surface
      environment where there is an excess of albumin molecules, coupled with
      restrictions in the conformational transitions of other surface-adsorbed proteins
      into hemostatically active forms.

PMID- 22652381
TI  - Microstructural stress relaxation mechanics in functionally different tendons.
AB  - Tendons experience widely varying loading conditions in vivo. They may be
      categorised by their function as either positional tendons, which are used for
      intricate movements and experience lower stress, or as energy storage tendons
      which act as highly stressed springs during locomotion. Structural and
      compositional differences between tendons are thought to enable an optimisation
      of their properties to suit their functional environment. However, little is
      known about structure-function relationships in tendon. This study adopts porcine
      flexor and extensor tendon fascicles as examples of high stress and low stress
      tendons, comparing their mechanical behaviour at the micro-level in order to
      understand their stress relaxation response. Stress-relaxation was shown to occur
      predominantly through sliding between collagen fibres. However, in the more
      highly stressed flexor tendon fascicles, more fibre reorganisation was evident
      when the tissue was exposed to low strains. By contrast, the low load extensor
      tendon fascicles appears to have less capacity for fibre reorganisation or
      shearing than the energy storage tendon, relying more heavily on fibril level
      relaxation. The extensor fascicles were also unable to sustain loads without
      rapid and complete stress relaxation. These findings highlight the need to
      optimise tendon repair solutions for specific tendons, and match tendon
      properties when using grafts in tendon repairs.

PMID- 22652382
TI  - Postural control adjustments during progressive inclination of the support
      surface in children.
AB  - One of the most important postural challenges in daily life is to continuously
      correct the destabilizing torque due to gravity that accelerates the body further
      away from the upright position. This study examined children's (7.9 years old)
      (n=7) and adults' (n=10) capacity to generate continuous corrective torque during
      a progressive perturbation. The experimental task was to maintain an upright
      quiet standing on a platform that gradually and slowly toes-down tilted to a
      maximum of 14 degrees  without visual cues. The vertical forces applied on the
      platform and the electromyograms from the tibialis anterior and the gastrocnemius
      were measured. The results showed that children had a different postural response
      to the perturbation than adults. When the platform was stationary before the
      inclination, children shifted their body weight backward whereas adults had a
      more balanced distribution of their weight. During the inclination, children
      applied a stronger forward force, suggesting a larger postero-anterior
      displacement of their body weight. Muscular activities were higher in children
      for both the tibialis anterior and the gastrocnemius, and their tibialis anterior
      activation profile was different. In conclusion, this study showed that in
      children aged from 7 to 10 years old neuromuscular responses were not mature
      enough to generate continuous postural corrective torque in response to the
      perturbation.

PMID- 22652383
TI  - Primary trigeminal afferents are the main source for stimulus-induced CGRP
      release into jugular vein blood and CSF.
AB  - BACKGROUND: Administration of inflammatory soup (IS) leads to a significant
      release of calcitonin gene-related peptide (CGRP). Whether IS-induced CGRP
      release originates in primary or secondary neurons of the trigeminovascular
      system has not been clarified. METHODS: We determined CGRP release into the
      external jugular vein and in cerebrospinal fluid (CSF) following intracisternal
      IS administration using an in vivo rat model. We further performed polymerase
      chain reaction (PCR) and immunohistochemistry of the trigeminal ganglion and
      brainstem (trigeminal nucleus caudalis). To further elucidate a primary vs.
      secondary origin, experiments were repeated after neonatal capsaicin treatment
      (NCT) as this treatment destroys primary trigeminal afferents. RESULTS: IS
      induced CGRP release into the external jugular vein and CSF were significantly
      reduced after NCT in both compartments but inhibition was more pronounced in
      jugular vein blood than in CSF. Baseline CGRP levels were not affected by NCT.
      PCR results show that following NCT, CGRP mRNA was significantly reduced in the
      trigeminal ganglion but not in the brainstem. Immunohistochemistry of the TG and
      brainstem support these results. CONCLUSIONS: We conclude that resting state CGRP
      levels can be maintained after trigeminal denervation of the meninges. However,
      for functional purposes primary trigeminal afferents are mandatory as they are
      the major source for stimulus-induced CGRP release.

PMID- 22652384
TI  - Effects of repetitive transcranial magnetic stimulation on somatosensory evoked
      potentials and high frequency oscillations in migraine.
AB  - BACKGROUND: In previous studies we found that high-frequency somatosensory
      oscillations (HFOs) reflecting thalamo-cortical activation were decreased in
      migraineurs between attacks and that high-frequency repetitive transcranial
      magnetic stimulation (rTMS) was able to normalize the habituation deficit of
      visual evoked potentials (VEPs). Here we study the effects of activating (10 Hz)
      or inhibiting (1 Hz) rTMS on conventional low-frequency (LF) and high-frequency
      somatosensory evoked potentials (SSEPs). SUBJECTS AND METHODS: rTMS was applied
      on the motor cortex of 13 healthy volunteers (HVs) and 13 migraine without aura
      (MO) patients. We measured N20-P25 LF-SSEP amplitude and habituation, and maximal
      peak-to-peak amplitude of early and late HFOs before and after rTMS. RESULTS: In
      HVs, 1 Hz rTMS significantly reduced the amplitude of the first LF-SSEP block and
      its habituation. In MO patients, 10 Hz rTMS increased the amplitude of the first
      block and induced habituation. Ten Hz rTMS produced an increase of late HFO in
      both groups, but more interestingly, in MO patients also significantly increased
      the early HFOs, which are reduced at baseline compared to those of HVs.
      CONCLUSIONS: These data confirm for SSEP that excitatory rTMS can normalize
      habituation in migraine patients and show that this is accompanied by early an
      HFO increase, which is thought to reflect thalamo-cortical activity. Taken
      together with similar effects we observed for VEPs, this finding supports the
      hypothesis that dysfunctioning thalamo-cortical loops may be responsible for the
      interictal habituation deficit in migraine.

PMID- 22652385
TI  - Cortical effect of oxaliplatin associated with sustained neuropathic pain:
      exacerbation of cortical activity and down-regulation of potassium channel
      expression in somatosensory cortex.
AB  - Oxaliplatin is a third-generation platinum-based chemotherapy drug that has
      gained importance in the treatment of advanced metastatic colorectal cancer. Its
      dose-limiting side effect is the production of chronic peripheral neuropathy.
      Using a modified model of oxaliplatin-induced sensory neuropathy, we investigated
      plastic changes at the cortical level as possible mechanisms underlying the
      chronicity of pain sensation in this model. Changes in gene expression were
      studied using DNA microarray which revealed that when oxaliplatin-treated animals
      displayed clinical neuropathic pain symptoms, including mechanical and thermal
      hypersensitivity, approximately 900 were down-regulated in the somatosensory
      cortex. Because of the known role of potassium channels in neuronal excitability,
      the study further focussed on the down-regulation of these channels as the
      possible molecular origin of cortical hyperexcitability. Quantification of the
      magnitude of neuronal extracellular signal-regulated kinase (ERK) phosphorylation
      in cortical neurons as a marker of neuronal activity revealed a 10-fold increase
      induced by oxaliplatin treatment, suggesting that neurons of cortical areas
      involved in transmission of painful stimuli undergo a chronic cortical
      excitability. We further demonstrated, using cortical injection of lentiviral
      vector shRNA against Kv2.2, that down-regulation of this potassium channel in
      naive animals induced a sustained thermal and mechanical hypersensitivity. In
      conclusion, although the detailed mechanisms leading to this cortical
      excitability are still unknown, our study demonstrated that a cortical down
      regulation of potassium channels could underlie pain chronicity in this model of
      chemotherapy-induced neuropathic pain.

PMID- 22652387
TI  - Validity of interview surveys.

PMID- 22652386
TI  - Intact 2D-form recognition despite impaired tactile spatial acuity in complex
      regional pain syndrome type I.
AB  - Tactile acuity measured by 2-point discrimination performance is impaired in
      patients with complex regional pain syndrome type I (CRPS-I). This is mirrored by
      pain-associated shrinkage of the cortical representation of the affected limb. We
      investigated whether, also, more complex tactile performance assessed by a
      dynamic 2D-form perception task is disturbed in CRPS-I patients. Therefore, we
      developed a Braille-like recognition task (BT) for geometrical dot pattern
      identification by dynamic touch. We studied 47 healthy volunteers (Study I) and
      compared them to 16 CRPS-I patients (Study II). Besides recognition time and
      error quote of the BT, we assessed static 2-point discrimination thresholds
      (TPDT). In healthy subjects, the performance in the BT correlated significantly
      with age and TPDT. In CRPS patients, TPDT was significantly increased on the
      affected side compared to sex- and age-matched controls from study I (2.98 +/-
      0.84 mm vs 2.05 +/- 0.82 mm, P<0.01). The performance in the BT was not impaired
      in CRPS-I patients (compared to sex- and age-matched controls from study I) and
      was not correlated to the TPDT. The intact 2D-form recognition ability in CRPS-I
      patients might be explained by intact dynamic tactile and proprioceptive
      functions, which appear to be uncompromised by the impaired static tactile
      perception, provided that the spacing of the dot pattern is above the individual
      tactile acuity. These intact 2D-form perception capacities may also be related to
      higher sensory integration functions like the visual system and intact semantic
      understanding, which may be spared by the cortical reorganization phenomena in
      CRPS-I.

PMID- 22652388
TI  - Bladder wall thickness and urodynamic correlation in children with primary
      nocturnal enuresis.
AB  - OBJECTIVE: To investigate the correlations between ultrasonographic bladder wall
      thickness (BWTh) and urodynamic study (UDS) findings and estimate the diagnostic
      value of BWTh for prediction of DO in children with monosymptomatic and non
      monosymptomatic primary nocturnal enuresis (PNE). PATIENTS AND METHODS:
      Ultrasound measurements (US) and UDS were performed on a total of 100 children,
      50 consecutive boys and 50 consecutive girls, 6-14 years old, with
      monosymptomatic PNE (group 1, n = 75), and non-monosymptomatic PNE (group 2, n =
      25). The US Protocol was specially designed for the evaluation of BWTh. All
      children underwent urodynamic studies for detailed assessment of any underlying
      bladder overactivity. Findings were compared between the two groups of patients.
      RESULTS: The mean BWTh was increased in the group 2 compared to the group 1 (mean
      +/- SD = 2.4 +/- 0.41 mm, mean +/- SD = 1.52 +/- 0.18 mm respectively, p < 0.05).
      Detrusor overactivity (DO) occurred in 23/75 (30.5%) children of the group 1 and
      in 17/25 (68%) children of the group 2 (p < 0.05). Comparing the BWTh between the
      two groups of patients and the UDS findings, it was found that BWTh was
      significantly correlated with DO(r = 0.92 and p < 0.001), children with DO
      presented significantly increased BWTh compared to those without (mean +/- SD =
      2.1 +/- 0.4 mm, mean +/- SD = 1.5 +/- 0.4 mm respectively, p < 0.05) and the
      maximum amplitude of DO occurred in 20 children who had non-monosymptomatic PNE.
      CONCLUSIONS: We suggest that BWTh could be applied as a screening tool to
      identify the cases of DO between the children with PNE. Children with non
      monosymptomatic PNE presented increased BWTh and higher percentages of DO.

PMID- 22652389
TI  - Is a closed bladder neck on preoperative videourodynamic studies an important
      factor for continence following augmentation ileocystoplasty in myelodysplastic
      patients?
AB  - PURPOSE: The aim of this study is to evaluate the importance of a closed bladder
      neck during videourodynamic (VUDE) studies in relation to urinary continence
      following augmentation ileocystoplasty in myelodysplastic patients. MATERIALS AND
      METHODS: We retrospectively reviewed the records of 24 myelodysplastic patients
      who underwent augmentation ileocystoplasty, using a standard technique. All
      patients had a closed bladder neck during preoperative VUDE studies. Their
      charts, imaging studies and VUDE data before and after surgery were analyzed. The
      mean follow-up after augmentation ileocystoplasty was 8.4 years. RESULTS: The
      overall incidence of urinary incontinence following the augmentation
      ileocystoplasty was 12.5%. Continence was achieved in 21 of 24 (87.5%) patients
      without additional outlet procedures. No significant upper tract changes
      developed. A clinically apparent tethered cord significantly hindered the
      achievement of continence. No significant correlation was found between the other
      videourodynamic parameters and obtaining continence. CONCLUSIONS: Our study
      provides evidence that a coexisting cord tethering in this myelodysplastic group
      can affect bladder neck morphology and function, and subsequent continence.

PMID- 22652390
TI  - Rare cause of dysuria: eosinophilic cystitis.
AB  - Eosinophilic cystitis is an inflammatory condition characterized by eosinophilic
      infiltration of whole layers of the bladder wall. The condition occurs more
      commonly in adults. We report a case of eosinophilic cystitis mimicking a bladder
      tumor in a 5-year-old boy with symptoms of dysuria and urinary incontinence. The
      diagnosis was confirmed by histopathology and he underwent clinical treatment
      with trimethoprim-sulfamethoxazole and antihistamine (cetirizine). The symptoms
      fully resolved in follow up, which is continuing. Although very rare,
      eosinophilic cystitis should be considered in cases of dysuria and increased
      bladder wall thickness but no identified urinary tract infection.

PMID- 22652391
TI  - Systems biology for complex diseases.

PMID- 22652392
TI  - Impaired reward learning and intact motivation after serotonin depletion in rats.
AB  - Aside from the well-known influence of serotonin (5-hydroxytryptamine, 5-HT) on
      emotional regulation, more recent investigations have revealed the importance of
      this monoamine in modulating cognition. Parachlorophenylalanine (PCPA) depletes 5
      HT by inhibiting tryptophan hydroxylase, the enzyme required for 5-HT synthesis
      and, if administered at sufficiently high doses, can result in a depletion of at
      least 90% of the brain's 5-HT levels. The present study assessed the long-lasting
      effects of widespread 5-HT depletions on two tasks of cognitive flexibility in
      Long Evans rats: effort discounting and reversal learning. We assessed
      performance on these tasks after administration of either 250 or 500 mg/kg PCPA
      or saline (SAL) on two consecutive days. Consistent with a previous report
      investigating the role of 5-HT on effort discounting, pretreatment with either
      dose of PCPA resulted in normal effortful choice: All rats continued to climb
      tall barriers to obtain large rewards and were not work-averse. Additionally,
      rats receiving the lower dose of PCPA displayed normal reversal learning.
      However, despite intact motivation to work for food rewards, rats receiving the
      largest dose of PCPA were unexpectedly impaired relative to SAL rats on the
      pretraining stages leading up to reversal learning, ultimately failing to
      approach and respond to the stimuli associated with reward. High performance
      liquid chromatography (HPLC) with electrochemical detection confirmed 5-HT, and
      not dopamine, levels in the ventromedial frontal cortex were correlated with this
      measure of associative reward learning.

PMID- 22652393
TI  - Anxious, hypoactive phenotype combined with motor deficits in Gtf2ird1 null mouse
      model relevant to Williams syndrome.
AB  - Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by a hemizygous
      deletion of around 28 genes on the long arm of chromosome 7 (7q11.23),
      characterized by a unique spectrum of behavioral impairments, including mental
      retardation, deficits in visuospatial constructive cognition, hypersociability,
      anxiety and simple phobias. Physical characteristics include dysmorphic faces,
      short stature, oculomotor deficits, gross and fine coordination impairments,
      diminished control of balance and mild extrapyramidal signs as well as gait
      abnormalities resembling gait hypokinesia. Genes near the distal deletion
      breakpoint appear to contribute most to the WBS cognitive and behavioral profile
      and include the GTF family of transcription factors: GTF2I, GTF2IRD1, GTF2IRD2.
      We have previously shown that heterozygous deletions of GTF2IRD1 in humans and
      homozygous deletion in mice contributes to craniofacial abnormalities. Here we
      show an important role of this gene in motor coordination and anxiety ascertained
      from extensive behavioral mouse phenotyping. Gtf2ird1 null mice showed lower body
      weight, decreased spontaneous and circadian locomotor activity, diminished motor
      coordination and strength, gait abnormalities, increased anxiety and an elevated
      endocrinological response to stress. Gtf2ird1 heterozygous mice displayed lower
      body weight and decreased circadian activity, but only minor motor coordination
      and anxiety-related behavioral dysfunctions. Our study strongly supports a role
      for GTF2IRD1 in the motoric and anxiety-related abnormalities seen in Williams
      Beuren syndrome, and suggests basal ganglia and potentially cerebellar
      abnormalities in Gtf2ird1 mice.

PMID- 22652394
TI  - Individual differences are critical in determining modafinil-induced behavioral
      sensitization and cross-sensitization with methamphetamine in mice.
AB  - Modafinil is a non-amphetaminic psychostimulant used therapeutically for sleep
      and psychiatric disorders. However, some studies indicate that modafinil can have
      addictive properties. The present study examined whether modafinil can produce
      behavioral sensitization in mice, an experience and drug-dependent behavioral
      adaptation, and if individual differences play a role in this process. We further
      tested context-related factors and cross-sensitization between modafinil and
      methamphetamine. Important individual differences in the behavioral sensitization
      of Swiss Albino mice were observed after repeated administration of 50 mg/kg
      modafinil (Experiment 1), or 1 mg/kg methamphetamine (Experiment 2). Only mice
      classified as sensitized subgroup developed clear behavioral sensitization to the
      drugs. After a withdrawal period, mice received challenges of modafinil
      (Experiment 1), or methamphetamine (Experiment 2) and locomotor activity was
      evaluated in the activity cages (previous context) and in the open field arena
      (new context) in order to evaluate the context dependency of behavioral
      sensitization. The expression of sensitization to modafinil, but not to
      methamphetamine, was affected by contextual testing conditions, since modafinil
      sensitized mice only expressed sensitization in the activity cage, but not in the
      open field. Subsequently, locomotor cross-sensitization between methamphetamine
      and modafinil was assessed by challenging modafinil-pretreated mice with 1mg/kg
      methamphetamine (Experiment 1), and methamphetamine-pretreated mice with 50mg/kg
      modafinil (Experiment 2). We observed a symmetrical cross-sensitization between
      the drugs only in those mice that were classified as sensitized subgroup. Our
      findings indicate that repeated exposure to modafinil induces behavioral
      sensitization only in some animals by similar neurobiological, but not
      contextual, mechanisms to those of methamphetamine.

PMID- 22652395
TI  - Photoperiod alters fear responses and basolateral amygdala neuronal spine density
      in white-footed mice (Peromyscus leucopus).
AB  - Photoperiodism is a biological phenomenon in which environmental day length is
      monitored to ascertain time of year to engage in seasonally appropriate
      adaptations. This trait is common among organisms living outside of the tropics.
      White-footed mice (Peromyscus leucopus) are small photoperiodic rodents which
      display a suite of adaptive responses to short day lengths, including reduced
      hippocampal volume, impairments in hippocampal-mediated memory, and enhanced
      hypothalamic-pituitary-adrenal axis reactivity. Because these photoperiodic
      changes in brain and behavior mirror some of the etiology of post-traumatic
      stress disorder (PTSD), we hypothesized that photoperiod may also alter fear
      memory and neuronal morphology within the hippocampus-basolateral amygdala
      prefrontal cortex fear circuit. Ten weeks of exposure to short days increased
      fear memory in an auditory-cued fear conditioning test. Short days also increased
      dendritic spine density of the neurons of the basolateral amygdala, without
      affecting morphology of pyramidal neurons within the infralimbic region of the
      medial prefrontal cortex. Taken together, photoperiodic phenotypic changes in
      brain morphology and physiology induced by a single environmental factor,
      exposure to short day lengths, affect responses to fearful stimuli in white
      footed mice. These results have potential implications for understanding seasonal
      changes in fear responsiveness, as well as for expanding translational animal
      models for studying gene-environment interactions underlying psychiatric
      diseases, such as PTSD.

PMID- 22652396
TI  - Synergistic effect of estradiol and fluoxetine in young adult and middle-aged
      female rats in two models of experimental depression.
AB  - The antidepressant effect of estrogens combined with antidepressants is
      controversial: some preclinical data showed that estrogens facilitate the effect
      of antidepressants in the forced swimming test (FST) in young adult rats, while
      others failed to find such effect in middle-aged rats in the chronic mild stress
      (CMS) model. In clinics similar differences were reported and may be due to the
      compounds, the depression model or type of depression, the experimental design,
      and the age of the subjects or the women's menopause stage. The objective of this
      study was to analyze the antidepressant-like effect of the combination of 17beta
      estradiol (E(2)) and fluoxetine (FLX) in young adults (2-4 months) and middle
      aged (12-14 months) ovariectomized (OVX) rats in two experimental models: FST and
      CMS. E(2) (5 and 10 MUg/rat) and FLX (2.5 and 10 mg/kg) per se dose-dependently
      reduced immobility in both age groups and, in young adults both compounds
      increased swimming, whereas in middle-aged rats they increased swimming and
      climbing. Analysis of the antidepressant-like effect of the combination of
      suboptimal doses of FLX (1.25 mg/kg) and E(2) (2.5 MUg/rat) showed a decrease in
      immobility and an increase in swimming in both age groups. In the CMS, chronic
      E(2) (2.5 MUg/rat) with FLX (1.25 mg/kg) augmented relative sucrose intake, but
      middle-aged rats responded 2 weeks earlier than young adults. These results show
      that the antidepressant-like effect of the combination of E(2) and FLX in young
      adult and middle-aged female rats is evidenced in the two animal models of
      depression: FST and CMS.

PMID- 22652397
TI  - Reduction of high pathogenicity avian influenza virus in eggs from chickens once
      or twice vaccinated with an oil-emulsified inactivated H5 avian influenza
      vaccine.
AB  - The negative impact of high pathogenicity avian influenza virus (HPAIV) infection
      on egg production and deposition of virus in eggs, as well as any protective
      effect of vaccination, is unknown. Individually housed non-vaccinated, sham
      vaccinated and inactivated H5N9 vaccinated Once or Twice adult White leghorn hens
      were challenged intranasally/intratracheally 3-weeks post-vaccination with H5N2
      HPAIV. The non-/sham-vaccinated layers experienced 100% mortality (0%
      survivability) within 3-4 days post-challenge (DPC), and major changes to
      reproductive parameters including precipitous drops in egg production (79-0% in
      <5 days), production of soft and thin-shelled eggs, and deposition of virus in
      albumin and yolk, and on the egg shell surface of 53% of eggs. By comparison, the
      three H5-vaccinated groups had 83%, 100% and 100% survivability after challenge;
      the two H5-vaccinated Once hens that died had low pre-challenge HI titers
      (GMT=16). H5-vaccinated Once or Twice groups maintained egg production after
      challenge (63%), but there was a mild and significant reduction in egg production
      as compared to pre-challenge egg production (79%). H5-vaccinated groups had
      reduced number of virus contaminated eggs (28%), and in most groups, reduced
      quantity of virus in contaminated eggs compared to non-/sham-vaccinated groups.
      No HPAIV-positive eggs were laid on or after 5 DPC. In conclusion, HPAIV
      infection had major negative impact on egg production and other reproductive
      parameters. H5-vaccination Once or Twice prevented declines in egg production
      after HPAIV challenge, reduced number of virus-infected eggs, and typically
      reduced the titer of virus in internal contents and on eggshell surface.

PMID- 22652398
TI  - Nuclear import of the influenza A virus transcriptional machinery.
AB  - Unusually for an RNA virus, influenza A viruses transcribe and replicate their
      genomes in the nuclei of infected cells. As a result the viral ribonucleoprotein
      complexes (RNPs), and their newly synthesised protein subunits, must interact
      with the host nuclear import machinery. In this review we discuss how the virus
      exploits nuclear import pathways to allow regulated and chaperoned assembly of
      RNPs in the nucleus, and describe how the import machinery itself can be a
      determinant of host tropism.

PMID- 22652399
TI  - Measles outbreak in Burkina Faso, 2009: a case-control study to determine risk
      factors and estimate vaccine effectiveness.
AB  - OBJECTIVE: We investigated a large measles outbreak that occurred in 2009 in
      Burkina Faso in order to describe the epidemic, assess risk factors associated
      with measles, and estimate measles vaccine effectiveness. METHODS: We reviewed
      national surveillance and measles vaccine coverage data, and conducted a case
      control study in three geographic areas. Case-patients were randomly selected
      from the national case-based measles surveillance database or, when a case
      patient could not be traced, were persons in the same community who experienced
      an illness meeting the WHO measles clinical case definition. Controls were
      matched to the same age stratum (age 1-14 years or age 15-30 years) and community
      as case-patients. Risk factors were assessed using conditional logistic
      regression. RESULTS: Lack of measles vaccination was the main risk factor for
      measles in all three geographic areas for children aged 1-14 years (adjusted
      matched odds ratio [aMOR] [95% confidence interval (CI)], 19.4 [2.4-155.9], 5.9
      [1.6-21.5], and 6.4 [1.8-23.0] in Bogodogo, Zorgho, and Sahel, respectively) and
      persons aged 15-30 years (aMOR [95% CI], 3.2 [1.1-9.7], 19.7 [3.3-infinity], 8.0
      [1.8-34.8] in Bogodogo, Zorgho, and Sahel, respectively). Among children aged 1
      14 years, VE of any measles vaccination prior to 2009 was 94% (95% CI, 45-99%) in
      Bogodogo, 87% (95% CI, 37-97%) in Zorgho, and 84% (95% CI, 41-96%) in Sahel. Main
      reasons for not receiving measles vaccination were lack of knowledge about
      vaccination campaigns or need for measles vaccination and absence during
      vaccination outreach or campaign activities. CONCLUSION: These results emphasize
      the need for improved strategies to reduce missed opportunities for vaccination
      and achieve high vaccination coverage nationwide in order to prevent large
      measles outbreaks and to continue progress toward measles mortality reduction.

PMID- 22652400
TI  - Two decades of hepatitis B vaccination in mentally retarded patients:
      effectiveness, antibody persistence and duration of immune memory.
AB  - INTRODUCTION: Institutionalized mentally retarded subjects are well-known to be
      at-risk for HBV infection. We studied the persistence of vaccine-induced anti-HBs
      antibodies and the robustness of the HBsAg-specific immune memory in this
      population, 18-20 years after the first vaccine dose. MATERIALS AND METHODS: Non
      immune residents of 4 institutions were immunized in 1984-1986. In 2004, 207
      subjects were bled to determine humoral and cellular immune memory. Immune
      response to a booster dose was evaluated in subjects with anti-HBs level <100
      IU/L. RESULTS: Four subjects showed anti-HBc seroconversion, without clinical
      implications. Pre-booster anti-HBs levels <100 IU/L were found in 45 subjects
      (22%); 34/39 (87%) responded with a rapid and high anti-HBs titer to the booster
      dose. Robust T and B cell memory was present pre- and post-booster. DISCUSSION
      AND CONCLUSION: Overall results confirm that hepatitis B vaccines are highly
      effective and immunogenic, and confer long-term persistence of antibodies and
      immune memory in an at-risk population.

PMID- 22652401
TI  - Calcineurin B subunit triggers innate immunity and acts as a novel Engerix-B HBV
      vaccine adjuvant.
AB  - We showed previously that calcineurin B subunit (CnB) protein activates innate
      immune cells including macrophages, monocytes and dendritic cells and acts as an
      adjuvant of a model antigen (ovalbumin) and a recombinant pneumolysin antigen,
      but the detailed mechanism is not clear and whether it can serve as an adjuvant
      of a commercial HBV vaccine is unknown. Here, we report that CnB promotes
      inflammatory cytokines production, splenocytes proliferation and NK lytic
      activity, and that CnB-induced inflammatory cytokines (IFN-gamma, IL-6, TNF
      alpha) production is dependent on integrin alphaM. Animal experiments demonstrate
      that CnB markedly increases the total anti-HBs antibodies in a dose and time
      dependent manner. Furthermore, CnB increases both anti-HBs IgM and anti-HBs IgG
      titers and changes the balance of IgG2a and IgG1. Combined use of CnB and CpG
      induces more cytokines production in splenocytes, as well as more anti-HBs
      antibodies production in vivo. These results reveal a probable mechanism of CnB
      induced inflammatory cytokines production and further demonstrate that CnB is a
      novel and effective adjuvant of Engerix-B HBV vaccine.

PMID- 22652402
TI  - Compatibility of ASO3-adjuvanted H1N1pdm09 and seasonal trivalent influenza
      vaccines in adults: results of a randomized, controlled trial.
AB  - When Canada chose a novel adjuvanted vaccine to combat the 2009 influenza
      pandemic, seasonal trivalent inactivated vaccine (TIV) was also available but
      compatibility of the two had not been assessed. To compare responses after
      concurrent or sequential administration of these vaccines, adults 20-59 years old
      were randomly assigned (1:1) to receive ASO3-adjuvanted H1N1pdm09 vaccine
      (Arepanrix, GSK, Quebec City, Quebec), with TIV (Vaxigrip, Sanofi Pasteur,
      Toronto) given concurrently or 21 days later. Blood was obtained at baseline and
      21 days after each vaccination to measure hemagglutination inhibition (HAI)
      titers. Adverse effects were assessed using symptom diaries and personal
      interviews. 282 participants completed the study (concurrent vaccines 145,
      sequential vaccines 137). HAI titers to H1N1pdm09 were >= 40 at baseline in 15
      18% of participants and following vaccination in 91-92%. Initially seropositive
      subjects (titer >= 10) had lower H1N1pdm09 geometric mean HAI titers (GMT) after
      concurrent than separate vaccinations (320.0 vs 476.5, p=0.039) but both exceeded
      GM responses of initially naive participants, which were unaffected by concurrent
      TIV. Responses to TIV were not lower after concurrent than separate vaccination.
      Adverse event rates were not increased by concurrent vaccinations above those
      with H1N1pdm09 vaccine alone. This adjuvanted H1N1pdm09 vaccine was immunogenic
      and compatible with concurrently administered TIV.

PMID- 22652403
TI  - Psychosocial determinants of parents' intention to vaccinate their newborn child
      against hepatitis B.
AB  - From October 2011, The Netherlands started to vaccinate all newborns against
      hepatitis B. The aim of the present study was to get insight in the psychosocial
      factors that determine parents' intention to vaccinate their child against
      hepatitis B, and to test whether intention to vaccinate is a good predictor of
      actual vaccination behaviour. In total, 2000 parents of newborns (0-2 weeks old)
      received a self-report questionnaire measuring intention towards hepatitis B
      vaccination and its psychosocial determinants (response rate 45.6%). Participants
      were invited for follow-up research and subsequently offered the opportunity to
      have their child vaccinated against hepatitis B. The findings showed that the
      large majority of parents intend to vaccinate their child against hepatitis B.
      The intention to vaccinate was most strongly determined by parents' attitude
      towards hepatitis B vaccination, which in turn was positively associated with
      perceived benefits of the vaccination and perceptions of the child's
      susceptibility to hepatitis B. The majority of the 246 parents that accepted the
      invitation for a follow-up study had their child vaccinated (83.7%). Intention
      was found to be a significant predictor of vaccination behaviour although less
      strong than expected. It is concluded that Dutch parents were positive towards
      hepatitis B vaccination in terms of both intention and behaviour. To further
      sustain parents' positive attitudes towards hepatitis B vaccination, educational
      campaigns should strengthen the benefits of vaccination along with emphasizing
      the child's risk to hepatitis B infection.

PMID- 22652405
TI  - Economic modelling assessment of the HPV quadrivalent vaccine in Brazil: a
      dynamic individual-based approach.
AB  - We examined the cost-effectiveness of the quadrivalent HPV vaccine for the pre
      adolescent female population of Brazil. Using demographic, epidemiological and
      cancer data, we developed a dynamic individual-based model representing the
      natural history of HPV/cervical cancer as well as the impact of screening and
      vaccination programmes. Assuming the current screening strategies, we calculated
      the incremental cost-effectiveness ratio (ICER) for cohorts with and without
      vaccination taking into account different combinations of vaccination coverage
      (50%, 70%, 90%) and cost per vaccinated woman (US$25, US$55, US$125, US$556). The
      results varied from cost-saving (coverage 50% or 70% and cost per vaccinated
      woman US$25) to 5950 US$/QALY (coverage 90% and cost per vaccinated 556 US$). In
      a scenario in which a booster shot was needed after 10 years in order to secure
      lifelong protection, the ICER resulted in 13,576 US$/QALY. Considering the very
      cost-effective and cost-effective thresholds based on Brazil's GDP per capita,
      apart from the booster scenario which would be deemed cost-effective, all the
      other scenarios would be deemed very cost-effective. Both the cost per dose of
      vaccine and discount rate (5%) had an important impact on the results.
      Vaccination in addition to the current screening programme is likely to save
      years of life and, depending on the cost of vaccination, may even save resources.
      Price negotiations between governments and manufacturers will be paramount in
      determining that the vaccine not only represents good value for money, but is
      also affordable in middle-income countries like Brazil.

PMID- 22652404
TI  - Post-exposure immunization against Francisella tularensis membrane proteins
      augments protective efficacy of gentamicin in a mouse model of pneumonic
      tularemia.
AB  - Successful treatment of pneumonic infection with Francisella tularensis, the
      causative agent of tularemia, requires rapid initiation of antibiotic therapy,
      yet even then treatment failures may occur. Consequently, new treatments are
      needed to enhance the effectiveness of antimicrobial therapy for acute pneumonic
      tularemia. In a prior study, immunization with F. tularensis membrane protein
      fraction (MPF) antigens 3 days prior to challenge was reported to induce
      significant protection from inhalational challenge. We therefore hypothesized
      that MPF immunization might also be effective in enhancing infection control if
      combined with antibiotic therapy and administered after infection as post
      exposure immunotherapy. To address this question, a 24h post-exposure treatment
      model of acute pulmonary Schu S4 strain of F. tularensis infection in BALB/c mice
      was used. Following exposure, mice were immunized with MPF and treated with low
      dose gentamicin, alone or in combination and the effects on survival, bacterial
      burden and dissemination were assessed. We found that immunization with MPF
      significantly increased the effectiveness of subtherapeutic gentamicin for post
      exposure treatment of pneumonic tularemia, with 100% of combination-treated mice
      surviving long-term. Bacterial burdens in the liver and spleen were significantly
      reduced in combination MPF-gentamicin treated mice at 7 days after challenge.
      Passively transferred antibodies against MPF antigens also increased the
      effectiveness of gentamicin therapy. Thus, we concluded that post-exposure
      immunization with MPF antigens was an effective means of enhancing conventional
      antimicrobial therapy for pneumonic tularemia.

PMID- 22652406
TI  - Increasing adolescent immunization by webinar: a brief provider intervention at
      federally qualified health centers.
AB  - OBJECTIVE: To evaluate a brief intervention to increase provision of adolescent
      vaccines at health centers that reach the medically underserved. METHOD: In April
      2010, clinical coordinators from 17 federally qualified health centers (serving
      7827 patients ages 12-17) participated in a competition to increase uptake of
      recommended adolescent vaccines: tetanus, diphtheria, and pertussis booster;
      meningococcal conjugate; and human papillomavirus. Vaccination coordinators
      attended a webinar that reviewed provider-based changes recommended by the CDC's
      Assessment, Feedback, Incentives, and eXchanges (AFIX) program and received
      weekly follow-up emails. Data on vaccine uptake came from the North Carolina
      Immunization Registry. RESULTS: Uptake of targeted adolescent vaccines increased
      during the one-month intervention period by about 1-2% (all p<.05). These small
      but reliable increases were greater than those observed for non-targeted vaccines
      (measles, mumps, and rubella; hepatitis B; and varicella). CONCLUSION: This AFIX
      webinar led to small increases in provision of targeted adolescent vaccines over
      a one-month period. Similar, sustainable programs at healthcare facilities,
      including federally qualified health centers that function as safety net
      providers for medically underserved populations could help reach populations with
      great need.

PMID- 22652407
TI  - Depth matters: cells grown on nano-porous anodic alumina respond to pore depth.
AB  - Recent experiments have shown unambiguously that living cells respond to the nano
      topography of surfaces they grow on-specifically, the fate of stem cells grown on
      nano-porous titania or alumina have been shown to be decided by the pore size.
      However, most experiments have focused on pore size or pitch. Here we show that
      in addition to pore size and pitch, the depth of the pores has a profound effect
      on cell morphology and the arrangement of the actin cytoskeleton.

PMID- 22652408
TI  - Autoantibodies to domain 1 of beta 2 glycoprotein 1: a promising candidate
      biomarker for risk management in antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by
      frequent clotting in arteries and veins and/or miscarriages. Autoantibodies to
      phospholipids and to beta 2 glycoprotein 1 (beta(2)GP1) play an important role in
      the pathogenesis of APS. Antibodies to the domain 1 of beta(2)GP1 (beta(2)GP1-D1)
      have been suggested as a risk marker for thrombosis and to a lesser extent for
      pregnancy complications in patients suffering from APS. Despite significant
      interest in anti-beta(2)GP1-D1 antibodies and a considerable research history,
      the number of studies is still limited and acceptance of the clinical
      significance of this biomarker is still evolving. The present review summarizes
      the current knowledge of anti-beta(2)GP1-D1 antibodies and provides insights on
      recent discoveries. Moreover, we present a suggested guideline for future studies
      to better understand and verify the clinical utility of anti-beta(2)GP1-D1
      antibodies.

PMID- 22652410
TI  - Cadmium tolerance in Brassica juncea roots and shoots is affected by antioxidant
      status and phytochelatin biosynthesis.
AB  - Indian mustard (Brassica juncea L. Czern.) tolerates high concentrations of heavy
      metals and is a promising species for the purpose of phytoextraction of cadmium
      (Cd) from metal-contaminated soils. This work investigates the extent to which
      antioxidant and metal sequestering mechanisms are responsible for this tolerance.
      To this end, seedlings of Indian mustard were grown for 7 days in 0, 50 or 200
      MUM Cd. Increasing Cd concentrations led to a progressive Cd accumulation in
      roots and shoots, accompanied by an organ-dependent alteration in mineral uptake,
      and a decrease in root/shoot length and fresh/dry weight. Cd negatively affected
      chlorophyll and carotenoid contents and activated the xanthophyll cycle,
      suggesting the need to protect the photosynthetic apparatus from photoinhibition.
      Shoots seemed to be less efficient than roots in ROS scavenging, as indicated by
      the different response to Cd stress shown by peroxidase and catalase activities
      and, solely with regard to the highest Cd concentration, by ascorbate level. Such
      a different antioxidant capacity might at least partly explain differences in the
      trend of lipid peroxidation observed in the two organs. Moreover, in both roots
      and shoots, glutathione and phytochelatin content markedly increased under Cd
      stress, regardless of the metal concentration involved.

PMID- 22652409
TI  - Activation of the damage-associated molecular pattern receptor P2X7 induces
      interleukin-1beta release from canine monocytes.
AB  - P2X7, a damage-associated molecular pattern receptor and adenosine 5'
      triphosphate (ATP)-gated cation channel, plays an important role in the
      activation of the NALP3 inflammasome and subsequent release of interleukin (IL)
      1beta from human monocytes; however its role in monocytes from other species
      including the dog remains poorly defined. This study investigated the role of
      P2X7 in canine monocytes, including its role in IL-1beta release. A fixed-time
      flow cytometric assay demonstrated that activation of P2X7 by extracellular ATP
      induces the uptake of the organic cation, YO-PRO-1(2+), into peripheral blood
      monocytes from various dog breeds, a process impaired by the specific P2X7
      antagonist, A438079. Moreover, in five different breeds, relative P2X7 function
      in monocytes was about half that of peripheral blood T cells but similar to that
      of peripheral blood B cells. Reverse transcription-PCR demonstrated the presence
      of P2X7, NALP3, caspase-1 and IL-1beta in LPS-primed canine monocytes.
      Immunoblotting confirmed the presence of P2X7 in LPS-primed canine monocytes.
      Finally, extracellular ATP induced YO-PRO-1(2+) uptake into and IL-1beta release
      from these cells, with both processes impaired by A438079. These results
      demonstrate that P2X7 activation induces the uptake of organic cations into and
      the release of IL-1beta from canine monocytes. These findings indicate that P2X7
      may play an important role in IL-1beta-dependent processes in dogs.

PMID- 22652411
TI  - Analysis of 49 autosomal SNPs in an Iraqi population.
AB  - Forty-nine of the 52 autosomal single nucleotide polymorphisms (SNPs) in the
      SNPforID 52plex were typed in 101 unrelated Iraqis living in Denmark. No
      significant deviation from HWE was found in all but one of the 49 SNP systems and
      no significant pairwise linkage disequilibrium was observed for any SNP pair.
      When 18 worldwide populations were compared (including populations in Iraq,
      Turkey, Israel, Pakistan, India, China, Taiwan, Japan, Siberia, Algeria, Somalia,
      Uganda, Mozambique, Angola, Nigeria, Denmark, Portugal, Spain), a significant
      global F(ST) value was obtained. All but six F(ST) values were statistically
      significant when pairwise comparisons were performed between the 18 populations.
      The Iraqi population did not show significant difference from the population in
      Turkey and it grouped together with other Middle-Eastern populations when a
      multidimensional scaling plot was drawn based on the pairwise F(ST) values. The
      combined mean match probability and the typical paternity index for trios were
      8.3*10(-20) and 259,000, respectively, for the Iraqi population.

PMID- 22652412
TI  - Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid
      arthritis.
AB  - Circulating IgG anti-cyclic citrullinated peptide antibodies (CCP) are highly
      specific for rheumatoid arthritis (RA) and prognostic of poor outcome. Serum IgA
      anti-CCP occurs in a subset of IgG-positive cases and relates to still more
      aggressive disease. Mucosal IgA-class antibodies, however, are generally
      associated with anti-inflammatory actions and systemic tolerance induction. In
      the present study, unstimulated salivary samples from 63 patients with
      established RA and 20 healthy persons were analysed by enzyme-linked immunoassay
      for the presence of IgA anti-CCP antibodies. To ensure antigen specificity, IgA
      reactivity with the corresponding uncitrullinated antigen, cyclic arginine
      peptide (CAP), was analysed and anti-CCP/anti-CAP ratios calculated.
      Retrospective data regarding disease activity and radiological outcome were
      achieved via medical records. Salivary IgA anti-CCP was found in 14/63 (22%)
      patients and one (5%) control (positive test=anti-CCP/anti-CAP ratio>1.5).
      Salivary IgA reactivity was dose-dependently inhibited by pre-incubation with
      soluble CCP to a degree strongly correlating with anti-CCP/anti-CAP ratio. In
      salivary IgA anti-CCP positive patients, joint erosions within 6 years of
      diagnosis was significantly lower (p=0.043), and at the time for diagnosis there
      was a trend towards lower erythrocyte sedimentation rate (p=0.071) and C-reactive
      protein (p=0.085). Contrasting to circulating IgG and IgA anti-CCP, our results
      imply that salivary IgA antibodies may be associated with a less severe outcome
      of RA. Hypothetically, this relates to an anti-inflammatory and protective
      immunomodulating role of secretory IgA-class autoantibodies against citrullinated
      antigens presented at mucosal surfaces.

PMID- 22652413
TI  - Increased intraepithelial (CD103+) CD8+ T cells in the airways of smokers with
      and without chronic obstructive pulmonary disease.
AB  - T cells are accumulated in the lungs of chronic obstructive pulmonary disease
      (COPD) patients. Intraepithelial T cells, expressing the integrin alphaE (CD103)
      beta7, and regulatory T cells have been implicated in pathogenesis of the
      disease. We asked whether COPD patients and smokers have altered frequencies of
      these T cells and if their phenotypes differ. A total of 40 never-smokers, 40
      smokers with normal lung function and 38 COPD patients (GOLD I and II), of which
      11 were ex-smokers, were included. T cells in bronchoalveolar lavage (BAL) fluid
      and peripheral blood were analysed for the expression of CD103, FOXP3 and markers
      of activation and differentiation using multi-colour flow cytometry. Smokers,
      regardless of airway obstruction, had significantly more CD8+CD103+ cells in
      their BAL fluid compared to never-smokers but less of those cells were CD27+CD69
      . Smokers, in particular those with chronic bronchitis, had a higher percentage
      of CD4+FOXP3+ T-regulatory BAL cells compared to never-smokers and COPD ex
      smokers. Chronic cigarette smoking leads to an accumulation of CD8+ T cells with
      an altered phenotype in the airway epithelium. The increased frequency of
      regulatory T cells may influence the ability to regulate smoke-induced
      inflammation which could be decisive for disease development. Our results further
      indicate a reversibility of smoke-induced changes.

PMID- 22652414
TI  - A multi-beach study of Staphylococcus aureus, MRSA, and enterococci in seawater
      and beach sand.
AB  - Incidences of Staphylococcus aureus and methicillin resistant S. aureus (MRSA)
      have risen worldwide prompting a need to better understand routes of human
      exposure and whether standard bacterial water quality monitoring practices
      adequately account for this potential threat. Beach water and sand samples were
      analyzed during summer months for S. aureus, enterococci, and MRSA at three
      southern California beaches (Avalon, Doheny, Malibu Surfrider). S. aureus
      frequently was detected in samples of seawater (59%, n = 328) and beach sand
      (53%, n = 358). MRSA sometimes was detected in seawater (1.6%, n = 366) and sand
      (2.7%, n = 366) at relatively low concentrations. Site specific differences were
      observed, with Avalon Beach presenting the highest concentrations of S. aureus
      and Malibu Surfrider the lowest in both seawater and sand. S. aureus
      concentrations in seawater and sand were correlated to each other and to a
      variety of other parameters. Multiple linear regression on the combined beach
      data indicated that significant explanatory variables for S. aureus in seawater
      were S. aureus in sand, water temperature, enterococci in seawater, and the
      number of swimmers. In sand, S. aureus concentrations were related to S. aureus
      in seawater, water temperature, enterococci in seawater, and inversely to surf
      height classification. Only the correlation to water temperature held for
      individually analyzed beaches and for S. aureus concentrations in both seawater
      and sand. To provide context for these results, the prevalence of S. aureus in
      sand was compared to published fomite studies, and results suggested that beach
      prevalence was similar to that in homes.

PMID- 22652415
TI  - Effect of short-term interferon-beta treatment on cytokines in multiple
      sclerosis: significant modulation of IL-17 and IL-23.
AB  - Therapeutic effect of interferon-beta (IFN-beta) treatment has been associated
      with modulation of the balance between Th1, Th17, Th2 and regulatory T (Treg)
      cells, whereas the impact of disease modifying drugs on Th9-immunity in multiple
      sclerosis (MS) has not been studied. To investigate the short-term effects of IFN
      beta treatment on cytokines in MS, we determined serum levels of IL-17, IL-23, IL
      10, IL-4, IFN-gamma, IL-9 and TGF-beta in relapsing remitting MS patients before
      and 2 months after IFN-beta treatment by ELISA. MS patients showed increased IL
      17, IL-23 and IL-4 levels and decreased IL-9 levels as compared to healthy
      controls. IFN-beta treatment only reduced IL-17 and IL-23 levels, whereas the
      levels of other cytokines remained unchanged. IFN-beta treatment appears to exert
      its earliest therapeutic effect on Th17-immunity. The influence of IL-9 on MS
      pathogenesis needs to be further studied.

PMID- 22652416
TI  - Interleukin-4 rs2243250 polymorphism is associated with asthma among Caucasians
      and related to atopic asthma.
AB  - Published data on the association between interleukin-4 (IL-4) rs2243250 (C-589T)
      polymorphism and asthma susceptibility are inconclusive. To derive a more precise
      estimation of the relationship, a meta-analysis was performed. A total of 17
      studies with 3037 asthma patients and 3032 healthy controls were included.
      Overall, significantly elevated asthma risk was associated with IL-4 T allele
      when all studies were pooled into the meta-analysis (CT vs. CC: OR=1.187, 95%
      CI=1.016-1.387; dominant model: OR=1.213, 95% CI=1.046-1.405). In the subgroup
      analysis by ethnicity, significantly increased risk was only found for Caucasians
      (TT vs. CC: OR=1.591, 95% CI=1.032-2.452; dominant model: OR=1.292, 95% CI=1.028
      1.624). When stratified by asthma type, statistically significantly elevated risk
      was only found in atopic asthma group (dominant model: OR=1.313, 95% CI=1.033
      1.667). Despite some limitations, this meta-analysis suggests that T allele at
      position -589 of the IL-4 gene promoter region is a low-penetrant risk factor for
      asthma development especially for Caucasians and atopic type.

PMID- 22652417
TI  - CXCL10 contributes to p38-mediated apoptosis in primary T lymphocytes in vitro.
AB  - CXCL10 is part of the group of interferon-stimulated genes and it plays an
      important role during different viral infections by inducing cell activation,
      chemotaxis and lymphocyte priming toward the Th1 phenotype. In this study, we
      investigated in vitro the effects of CXCL10 in activated human primary T
      lymphocytes in terms of apoptosis or survival, and delineated the signaling
      pathways that are involved. CXCL10, in combination with IL-2 and/or IFNalpha,
      induces apoptosis in T lymphocytes. Moreover, CXCL10-induced activation of CXCR3
      also triggers pro-survival signals that can be blocked by pertussis toxin. The
      analysis of the downstream signaling kinases shows that apoptosis is p38 MAPK
      dependent and the pro-survival signals rely on the sustained activation of PI3K
      and the transient activation of Akt. On the other hand, the transient activation
      of p44/p42 ERK did not have an impact on T lymphocyte survival. We propose an
      immunological model in which CXCL10, together with other co-stimulating
      cytokines, participates in the activation of T lymphocytes, promotes survival and
      expansion of certain lymphocyte subsets, and induces chemotaxis toward the
      infected tissues. On the other hand, CXCL10 might contribute to the triggering of
      apoptosis in other subsets of T lymphocytes, including those lymphocytes that
      were transiently activated but later lacked the appropriate sets of specific co
      stimulating signals to ensure their survival.

PMID- 22652418
TI  - Enzymatic autoantibody glycan hydrolysis alleviates autoimmunity against type VII
      collagen.
AB  - Autoantibody-mediated diseases comprise a heterogeneous group of disorders in
      which the pathogenic potential of autoantibodies has been clearly demonstrated.
      In general, their treatment relies on the long-term use of systemic
      corticosteroids and other immunosuppressants that are associated with
      considerable adverse reactions. EndoS, an endoglycosidase derived from
      Streptococcus pyogenes, specifically hydrolyzes the N-linked glycan of native IgG
      and has previously been shown to modulate the interaction between the Fc portion
      of autoantibody and Fcgamma receptors on leukocytes. Here, different models of
      autoimmunity to type VII collagen, a structural protein of the dermal-epidermal
      junction (DEJ), were employed to explore the therapeutic potential of EndoS.
      First, pretreatment of otherwise pathogenic anti-murine type VII collagen (mCOL7)
      IgG with EndoS significantly reduced split formation at the DEJ in cryosections
      of murine skin and abrogated clinical disease in mice. Next, the effect of EndoS
      was also seen when the enzyme was injected into mice after pathogenic anti-mCOL7
      IgG had been administered. Finally, to mimic the patient situation even closer,
      EndoS was applied in mice that had already developed clinical disease after
      immunization with mCOL7. In all EndoS-treated mice, disease progression was
      stopped, and in the majority of mice, clinical disease even regressed. Of note,
      EndoS was shown to hydrolyze already in vivo-bound pathogenic autoantibodies. In
      addition, EndoS treatment decreased lesional expression of activating FcgammaRs
      while increasing FcgammaRIIB expression.

PMID- 22652419
TI  - Pollination function transferred: modified tepals of Albuca (Hyacinthaceae) serve
      as secondary stigmas.
AB  - BACKGROUND AND AIMS: The stigma, a structure which serves as a site for pollen
      receipt and germination, has been assumed to have evolved once, as a modification
      of carpels, in early angiosperms. Here it is shown that a functional stigma has
      evolved secondarily from modified tepals in some Albuca species (Hyacinthaceae).
      METHODS: Deposition of pollen on Albuca floral organs by bees was recorded.
      Pollen germination and fruit set was measured in flowers that had pollen
      deposited solely on their tepals or had their tepal tips experimentally isolated
      or removed after pollination. KEY RESULTS: Leafcutter bees deposit pollen onto
      the papillate apices of the inner tepals of Albuca flowers. Pollen germinates in
      tepal-derived fluid secreted 2 or 3 d after anthesis and pollen tubes
      subsequently penetrate the style during flower wilting. Application of cross
      pollen to the inner tepal apices of A. setosa flowers led to high fruit set. No
      fruits were produced in pollinated flowers in which the inner tepals were
      mechanically isolated or removed. CONCLUSIONS: Pollen capture by tepals in the
      Albuca clade probably evolved in response to selection for floral morphology that
      maximizes the accuracy of pollen transfer. These findings show how pollination
      function can be transferred among floral organs, and shed light on how the
      original angiosperm stigma developed from sporophylls.

PMID- 22652420
TI  - Arabinogalactan-protein secretion is associated with the acquisition of stigmatic
      receptivity in the apple flower.
AB  - BACKGROUND AND AIMS: Stigmatic receptivity plays a clear role in pollination
      dynamics; however, little is known about the factors that confer to a stigma the
      competence to be receptive for the germination of pollen grains. In this work, a
      developmental approach is used to evaluate the acquisition of stigmatic
      receptivity and its relationship with a possible change in arabinogalactan
      proteins (AGPs). METHODS: Flowers of the domestic apple, Malus * domestica, were
      assessed for their capacity to support pollen germination at different
      developmental stages. Stigmas from these same stages were characterized
      morphologically and different AGP epitopes detected by immunocytochemistry. KEY
      RESULTS: Acquisition of stigmatic receptivity and the secretion of classical AGPs
      from stigmatic cells occurred concurrently and following the same spatial
      distribution. While in unpollinated stigmas AGPs appeared unaltered, in cross
      pollinated stigmas AGPs epitopes vanished as pollen tubes passed by. CONCLUSIONS:
      The concurrent secretion of AGPs with the acquisition of stigmatic receptivity,
      together with the differential response in unpollinated and cross-pollinated
      pistils point out a role of AGPs in supporting pollen tube germination and
      strongly suggest that secretion of AGPs is associated with the acquisition of
      stigma receptivity.

PMID- 22652421
TI  - Expression of floral MADS-box genes in Sinofranchetia chinensis
      (Lardizabalaceae): implications for the nature of the nectar leaves.
AB  - BACKGROUND AND AIMS: The perianths of the Lardizabalaceae are diverse. The second
      whorl floral organs of Sinofranchetia chinensis (Lardizabalaceae) are nectar
      leaves. The aim of this study was to explore the nature of this type of floral
      organ, and to determine its relationship to nectar leaves in other Ranunculales
      species, and to other floral organs in Sinofranchetia chinensis. METHODS:
      Approaches of evolutionary developmental biology were used, including 3' RACE
      (rapid amplification of cDNA ends) for isolating floral MADS-box genes,
      phylogenetic analysis for reconstructing gene evolutionary history, in situ
      hybridization and tissue-specific RT-PCR for identifying gene expression patterns
      and SEM (scanning electron microscopy) for observing the epidermal cell
      morphology of floral organs. KEY RESULTS: Fourteen new floral MADS-box genes were
      isolated from Sinofranchetia chinensis and from two other species of
      Lardizabalaceae, Holboellia grandiflora and Decaisnea insignis. The phylogenetic
      analysis of AP3-like genes in Ranunculales showed that three AP3 paralogues from
      Sinofranchetia chinensis belong to the AP3-I, -II and -III lineages. In situ
      hybridization results showed that SIchAP3-3 is significantly expressed only in
      nectar leaves at the late stages of floral development, and SIchAG, a C-class
      MADS-box gene, is expressed not only in stamens and carpels, but also in nectar
      leaves. SEM observation revealed that the adaxial surface of nectar leaves is
      covered with conical epidermal cells, a hallmark of petaloidy. CONCLUSIONS: The
      gene expression data imply that the nectar leaves in S. chinensis might share a
      similar genetic regulatory code with other nectar leaves in Ranunculales species.
      Based on gene expression and morphological evidence, it is considered that the
      nectar leaves in S. chinensis could be referred to as petals. Furthermore, the
      study supports the hypothesis that the nectar leaves in some Ranunculales species
      might be derived from stamens.

PMID- 22652422
TI  - Can post-ictal intervention prevent sudden unexpected death in epilepsy? A report
      of two cases.
AB  - It has been suggested that alerting caregivers to seizure occurrence so they can
      deliver post-ictal care may be an effective way to prevent sudden unexpected
      death in epilepsy (SUDEP). We report two cases of SUDEP referred for an expert
      medical-legal review for which immediate post-ictal intervention was ineffective.
      In both patients, prompt resuscitation procedures by medical personnel after
      seizures failed to prevent SUDEP. These cases demonstrate that some seizures may
      lead to death even with expert intervention almost immediately after the seizure
      occurs. It is possible that for some SUDEP cases, seizures may trigger an
      irreversible cascade of cardiopulmonary and cerebral changes that lead to death.
      Further studies in the pathophysiology of SUDEP may help identify alternative
      prevention strategies.

PMID- 22652423
TI  - Seizure diaries for clinical research and practice: limitations and future
      prospects.
AB  - PURPOSE: An NINDS-sponsored conference in April of 2011 reviewed issues in
      epilepsy clinical trials. One goal was to clarify new electronic methods for
      recording seizure information and other data in clinical trials. METHODS: This
      selective literature review and compilation of expert opinion considers
      advantages and limitations of traditional paper-based seizure diaries in
      comparison to electronic diaries. KEY FINDINGS: Seizure diaries are a type of
      patient-reported outcome. All seizure diaries depend first on accurate
      recognition and recording of seizures, which is a problem since about half of
      seizures recorded during video-EEG monitoring are not known to the patient.
      Reliability of recording is another key issue. Diaries may not be at hand after a
      seizure, lost or not brought to clinic visits. On-line electronic diaries have
      several potential advantages over paper diaries. Smartphones are increasingly
      accessible as data entry gateways. Data are not easily lost and are accessible
      from clinic. Entries can be time-stamped and provide immediate feedback,
      validation or reminders. Data can also can be graphed and pasted into an EMR.
      Disadvantages include need for digital sophistication, higher cost, increased
      setup time, and requiring attention to potential privacy issues. The Epilepsy
      Diary by epilepsy.com and Irody, Inc. has over 13,000 registrants and
      SeizureTracker over 10,000, and both are used for clinical and research purposes.
      Some studies have documented patient preference and increased compliance for
      electronic versus paper diaries. Seizure diaries can be challenging in the
      pediatric population. Children often have multiple seizure types and limited
      reporting of subjective symptoms. Multiple caregivers during the day require more
      training to produce reliable and consistent data. Diary-based observational
      studies have the advantages of low cost, allowing locus-of-control by the patient
      and testing in a "real-world" environment. Diary-based studies can also be useful
      as descriptive "snapshots" of a population. However, the type of information
      available is very different from that obtained by prospective controlled studies.
      The act of self-recording observations may itself influence the observation, for
      example, by causing the subject to attend more vigilantly to seizures after
      changing medication. Pivotal anti-seizure drug or device trials still mostly rely
      on paper-based seizure diaries. Industry is aware of the potential advantages of
      electronic diaries, particularly, the promise of real-time transmission of data,
      time-stamping of entries, reminders to subjects, and potentially automatic
      interfaces to other devices. However, until diaries are validated as research
      tools and the regulatory environment becomes clearer, adoption of new types of
      diaries as markers for a primary study outcome will be cautious. SIGNIFICANCE:
      Recommendations from the conference included: further studies of validity of
      epilepsy diaries and how they can be used to improve adherence; use and further
      development of core data sets, such as the one recently developed by NINDS;
      encouraging links of diaries to electronic sensors; development of diary privacy
      and legal policies; examination of special pediatric diary issues; development of
      principles for observational research from diaries; and work with the FDA to make
      electronic diaries more useful in industry-sponsored clinical trials.

PMID- 22652424
TI  - Acute psychosis during the postictal period in a patient with idiopathic
      generalized epilepsy: postictal psychosis or aggravation of schizophrenia? A case
      report and review of the literature.
AB  - Postictal psychoses are common comorbid conditions of temporal lobe epilepsy and
      are reported to be characterized by affective changes. However, postictal
      psychoses are rare among patients with idiopathic generalized epilepsy, and the
      causal relationship between postictal psychoses and idiopathic generalized
      epilepsy is unknown. Here, we report the case of a man who had idiopathic
      generalized epilepsy and experienced 4 episodes of schizophrenia-like interictal
      psychosis before the age of 41 years. At the age of 56 years, he experienced a
      generalized tonic-clonic seizure for the first time in 15 years and developed
      psychotic symptoms on the next day. Notably, in addition to the schizophrenia
      like symptoms, the patient experienced mania-like symptoms such as elated mood,
      grandiose delusions, agitation, and pressured speech during the last psychotic
      episode in the postictal period. It was suspected that postictal neuronal
      processes and a predisposition to endogenous psychosis both contributed to the
      psychopathology of this episode.

PMID- 22652425
TI  - Validation of the Italian version of the Neurological Disorders Depression
      Inventory for Epilepsy (NDDI-E).
AB  - The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was
      developed for the rapid detection of a major depressive episode in people with
      epilepsy. It has been proven to be a user-friendly screening instrument. This
      study describes the development, validation, and psychometric properties of the
      Italian version of the NDDI-E. A consecutive sample of 120 outpatients with
      epilepsy has been assessed using the M.I.N.I. Plus version 5.0.0 and the NDDI-E.
      All patients had no major difficulties in understanding or answering the
      questions of the Italian version. Cronbach's alpha coefficient was 0.851.
      Receiver operating characteristic analysis showed an area under the curve of
      0.943 (CI95%=0.902-0.985; SE 0.021; p<0.001), a cut off score of 13, a
      sensitivity of 86.2%, a specificity of 89%, a positive predictive value of 71.4%,
      and a negative predictive value of 95.3%.

PMID- 22652426
TI  - A dioxin response element in the multiple cloning site of the pGL3 luciferase
      reporter influences transcriptional activity.
AB  - Luciferase reporter plasmids (pGL3 backbone, Promega) have been utilized to
      characterize the transcriptional effects of the environmental contaminant 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon receptor (AhR)
      ligands. Following ligand activation, the AhR and its dimerization partner AhR
      nuclear translocator (ARNT) regulate transcription by binding dioxin response
      elements (DREs) in regulatory regions of dioxin-sensitive genes. Upon sequencing
      of our luciferase reporters, we unexpectedly identified a DRE core motif within
      the multiple cloning site (mcsDRE) of the pGL3 luciferase plasmid backbone in a
      subset of our reporters. Therefore, the objective of this study was to determine
      if the mcsDRE inadvertently influences reporter activity. Utilizing deletional
      analysis we determined that the mcsDRE did significantly alter the
      transcriptional effect induced by TCDD. Since many chemicals have been shown to
      interact with the AhR and influence transcription through the DRE, the presence
      of the mcsDRE in the pGL3 luciferase plasmid may inappropriately influence
      promoter and enhancer analysis. As such, insertion of regulatory elements into
      pGL3 reporters should be designed to avoid retaining the mcsDRE core motif
      (GCGTG) and currently utilized pGL3 reporters should be evaluated for the
      presence of the mcsDRE.

PMID- 22652427
TI  - Comparisons of mammalian Giardia duodenalis assemblages based on the beta
      giardin, glutamate dehydrogenase and triose phosphate isomerase genes.
AB  - The objective of this study was to determine and compare the assemblages of
      Giardia duodenalis isolated from mammalian fecal samples using the beta-giardin
      (bg), glutamate dehydrogenase (gdh) and triosephosphate isomerase (tpi) genes. A
      total of 202 samples, either submitted to the Veterinary Diagnostic Laboratory
      (Parasitology) at Colorado State University or part of ongoing research studies,
      were typed. A subset of 50 dog samples were also assessed by the tpi-D-specific
      primers. Of these, 183 were from dogs, 13 were from cats, two were from llamas,
      and one each was from a calf, an alpaca, a sheep, and a horse. The majority of
      the dogs (171 of 183 isolates) in this study were infected with only dog-adapted
      Assemblage C or D. The tpi-D-specific primers confirmed that 28 of the samples
      that typed as Assemblage D by the bg and gdh genes were also Assemblage D by the
      tpi-D-specific primers. Only 12 isolates were Assemblage A alone or Assemblage A
      and Assemblage C or D. Of the 13 cat isolates, seven were Assemblage F, two were
      Assemblage D, three were Assemblage A and 1 contained both Assemblages C and D.
      The calf isolate was Assemblage E (gdh, tpi) and the alpaca (bg, gdh), llamas
      (gdh), sheep (bg, gdh, tpi) and horse (tpi) isolates were all Assemblage A. When
      the assemblage could be determined for more than one gene, 91 of 117 dog isolates
      gave consistent results and 8 of 9 cat isolates gave consistent results.

PMID- 22652428
TI  - Recombinant human bone morphogenetic protein-2 released from polyurethane-based
      scaffolds promotes early osteogenic differentiation of human mesenchymal stem
      cells.
AB  - The purposes of this study were to determine the pharmacokinetics of recombinant
      human bone morphogenetic protein-2 (rhBMP-2) from a polyurethane (PUR)-based
      porous scaffold and to determine the biological responses of human mesenchymal
      stem cells (hMSCs) to the rhBMP-2 released from those scaffolds. The rhBMP-2 was
      incorporated into the PUR three-dimensional (3D) porous scaffolds and release
      profiles were determined using enzyme-linked immunosorbent assay. The bioactivity
      of the rhBMP-2 containing releasates was determined using hMSCs and compared with
      exogenous rhBMP-2. Release of rhBMP-2 from PUR-based systems was bi-phasic and
      characterized by an initial burst followed by a sustained release for up to 21
      days. Expression of alkaline phosphatase activity by hMSCs treated with the rhBMP
      2 releasates was significantly greater than the cells alone (control) throughout
      the time periods. Furthermore, after 14 days of culture, the hMSCs cultured with
      rhBMP-2 releasate had a greater amount of mineralization compared to exogenous
      rhBMP-2. Overall, the rhBMP-2 release from the PUR-based scaffolds was sustained
      for 21 days and the releasates appeared to be bioactive and promoted earlier
      osteogenic differentiation and mineralization of hMSCs than the exogenous rhBMP
      2.

PMID- 22652429
TI  - Inflammatory milieu as an early marker of kidney injury in offspring rats from
      diabetic mothers.
AB  - The present study investigated the early presence of inflammatory response in
      renal tissue of young offspring from diabetic mothers. The effect of L-arginine
      (L-arg) supplementation was also investigated. The offspring was divided into
      four groups: group CO (controls); group DO (diabetic offspring); group CA (CO
      receiving 2% L-arg solution) and group DA (DO receiving the 2% L-arg solution).
      Glycemia, arterial pressure and renal function were evaluated; gene and protein
      expression of pro-inflammatory cytokines were also measured. Blood pressure
      levels were significantly increased in 2 and 6 month-old DO rats, whereas L-arg
      administration caused a significant decrease in the DA group, at both ages. DO
      rats showed a significantly blunted glycemic response to exogenous insulin. In 2
      month-old DO animals, renal protein expression of pro-inflammatory molecules was
      significantly increased. At six months of age, we also observed an increase in
      gene expression of pro-inflammatory molecules, whereas L-arg supplementation
      prevented this increase at both ages. Our data suggest that activation of
      inflammatory pathways is present early in the kidney of DO rats, and that L-arg
      can attenuate the expression of these markers of tissue inflammation. Our results
      also reinforce the concept that intrauterine environmental factors are a
      fundamental determinant in the development of metabolic and vascular diseases
      later in life.

PMID- 22652430
TI  - The genetic deletion of Mas abolishes salt induced hypertension in mice.
AB  - The G protein-coupled receptor Mas is a physiological antagonist of the
      angiotensin II type 1 receptor and is associated with angiotensin-(1-7)
      signaling. We investigated the effect of Mas-deficiency on blood pressure
      regulation under physiological conditions and salt load using radiotelemetry. Mas
      knockout mice and their wild-type controls received a telemetry implant in the
      carotid artery. One week after surgery, animals were monitored for 3 days
      receiving normal diet (0.6% NaCl) followed by one-week high-salt diet (8% NaCl).
      Under same high-salt diet, another set of mice was placed in individual metabolic
      cages for 4 days. Basal mean arterial pressure, heart rate and locomotor activity
      displayed normal day-night rhythm in Mas-deficient mice. Mas-knockout mice were
      normotensive. High dietary NaCl ingestion did not alter heart rate or locomotor
      activity in both groups, but significantly increased night time mean arterial
      pressure in control mice whereas this increase was blunted in Mas-deficient mice.
      Baseline food and water intake and urine osmolality were not different between
      both genotypes. Under high-salt diet, water consumption and food intake were
      equally increased in wild-type controls and Mas-knockout, but urinary
      electrolytes and osmolality were significantly higher in Mas-knockout. Taken
      together, basal hemodynamic parameters are unchanged in Mas-knockout mice. In
      contrast to wild-type controls, telemetric mean arterial pressure measurement
      revealed salt resistance in Mas-deficient animals, probably due to their higher
      urinary NaCl excretion. This is the first direct proof that Mas blockade might be
      a new option in the treatment of salt-sensitive hypertension.

PMID- 22652431
TI  - Effects of intraperitoneal administration of the GABAB receptor positive
      allosteric modulator 2,6-di tert-butyl-4-(2-hydroxy-2,2-dimethyl-propyl)-phenol
      (CGP7930) on food intake in non-deprived rats.
AB  - gamma-Aminobutyric acid-(B) (GABA(B)) receptor positive allosteric modulators
      (PAMs) act on an allosteric site on the GABA(B) receptor to potentiate the
      effects of GABA and GABA(B) receptor agonists. It has previously been
      demonstrated that the GABA(B) receptor agonist baclofen increases food intake in
      non-deprived rats. The aim of this study was to investigate whether the GABA(B)
      receptor PAM 2,6-di tert-butyl-4-(2-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930)
      would (i) increase food intake, and (ii) potentiate the hyperphagic effects of
      baclofen in rats. In Experiment 1, the effects of intraperitoneal (i.p.)
      administration of CGP7930 (1, 6 and 12 mg/kg) was investigated on food intake in
      non-deprived male Wistar rats. The 12 mg/kg dose of CGP7930 significantly
      increased cumulative food intake 30, 60 and 120 min (P<0.05, in each case) after
      administration. The 1 and 6 mg/kg doses were without effect. In Experiment 2, the
      effects of pretreatment with CGP7930 (6 mg/kg; i.p.) 5 min prior to
      administration of baclofen (2mg/kg, i.p.) was investigated on 30min cumulative
      food intake in non-deprived male Wistar rats. Baclofen (2mg/kg) significantly
      increased food intake compared with vehicle treatment (P<0.01). CGP7930 (6 mg/kg)
      had no effect on feeding. However, pretreatment with CGP7930 (6 mg/kg)
      significantly potentiated the hyperphagic effects of baclofen (2mg/kg) (P<0.01).
      These findings show that CGP7930 increases food intake and enhances the
      hyperphagic effects of baclofen, and are consistent with in vitro studies that
      suggest that it potentiates the effects of endogenous GABA and GABA(B) receptor
      agonists by allosteric modulation of the GABA(B) receptor.

PMID- 22652432
TI  - Characterization of an intracellular ATP assay for evaluating the viability of
      live attenuated mycobacterial vaccine preparations.
AB  - The viability of BCG vaccine has traditionally been monitored using a colony
      forming unit (CFU) assay. Despite its widespread use, results from the CFU assay
      can be highly variable because of the characteristic clumping of mycobacteria,
      their requirement for complex growth media, and the three week incubation period
      needed to cultivate slow-growing mycobacteria. In this study, we evaluated
      whether an ATP luminescence assay (which measures intracellular ATP content)
      could be used to rapidly estimate the viability of lyophilized and/or frozen
      preparations of six different BCG vaccine preparations - Danish, Tokyo, Russia,
      Brazil, Tice, and Pasteur - and two live attenuated mycobacterial vaccine
      candidates - a DeltalysADeltapanCD M. tuberculosis strain and a DeltammaA4 BCG
      vaccine mutant. For every vaccine tested, a significant correlation was observed
      between intracellular ATP concentrations and the number of viable attenuated
      bacilli. However, the extractable intracellular ATP levels detected per cell
      among the different live vaccines varied suggesting that validated ATP
      luminescence assays with specific appropriate standards must be developed for
      each individual live attenuated vaccine preparation. Overall, these data indicate
      that the ATP luminescence assay is a rapid, sensitive, and reliable alternative
      method for quantifying the viability of varying live attenuated mycobacterial
      vaccine preparations.

PMID- 22652433
TI  - High-resolution melt PCR analysis for rapid identification of Chlamydia abortus
      live vaccine strain 1B among C. abortus strains and field isolates.
AB  - We describe a novel high-resolution melt assay that clearly differentiates
      Chlamydia abortus live vaccine strain 1B from field C. abortus strains and field
      wild-type isolates based on previously described single nucleotide polymorphisms.
      This modern genotyping technique is inexpensive, easy to use, and less time
      consuming than PCR-RFLP.

PMID- 22652434
TI  - RNA in all its forms.

PMID- 22652435
TI  - Primitive polypoid granular cell tumor.

PMID- 22652436
TI  - Editor's perspectives - June 2012.

PMID- 22652438
TI  - The paracrine role of 5-HT in the control of gill blood flow.
AB  - Storage of serotonin in teleost gill cells has been detected in neurons,
      polymorphous granular cells and in neuroepithelial cells. Innervation from the
      glossopharyngeal nerve (first gill arch) and the vagus nerve (all gill arches)
      carries afferent as well as efferent fibers. This innervation extends to the
      efferent filament artery, including the sphincter muscle associated with the
      efferent filament artery, but except for the Antarctic fish does not reach the
      afferent filament artery. Serotonergic nerves as well as neuroepithelial cells
      have been shown to release serotonin, while very little is known about the
      polymorphous granular cells. The paracrine action of the released serotonin may
      affect vascular smooth muscle cells and pillar cells, which also contain
      contractile filaments. Already the earliest functional studies revealed a severe
      increase in branchial resistance as a result of serotonin application, combined
      with an increase in the perfusion of the arterio-venous path and the central
      sinus spaces of the gills. Pharmacological analysis demonstrated that this is a
      serotonin specific effect, which in Antarctic fish is due to activation of the 5
      HT(2) receptor, while inhibition of the 5-HT(1) receptor does not reduce the
      serotonin induced vasoconstriction of gill blood vessels. Hypoxic degranulation
      of serotonergic cells evoked the hypothesis that serotonergic vasoconstriction
      might result in more even and overall better perfusion of gill lamellae.
      Microscopic analysis indicated, however, that perfusion of distal lamellae was
      reduced after serotonin application. Furthermore, a serotonergic increase in
      branchial resistance caused a decrease in dorsal arterial oxygen saturation, not
      an increase as would be expected as a result of a better perfusion of gill
      lamellae. A detailed analysis of hypoxic effects on gill perfusion revealed that
      hypoxia induced changes in gill blood flow are due to cholinergic effects, but
      serotonergic influences could not be detected. These observations contradict the
      hypothesis that serotonergic vasoconstriction might support hypoxic gas exchange.
      The functional significance of the serotonergic control of gill blood flow
      therefore is not yet totally clear. Recent observations indicate that specific
      inhibitors of serotonin re-uptake accumulate in freshwater and in estuaries.
      Considering the negative effect of serotonin on arterial blood oxygenation this
      may become a threat to teleost species.

PMID- 22652437
TI  - The effect of acute non-invasive ventilation on corticospinal pathways to the
      respiratory muscles in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease is associated with altered cortical
      excitability. The relevance of this to the need for non-invasive ventilation is
      not known. We assessed the diaphragm response to transcranial magnetic
      stimulation in terms of motor threshold and latency as well as assessing
      intracortical excitability using paired stimulation in eight long-term users and
      six non-users of home ventilation with COPD. Overall, intracortical facilitation
      was strongly correlated with inspiratory muscle strength (r2 0.72, p<0.001)
      whereas intracortical inhibition was correlated with PaCO2 (r2 0.51, p=0.01). The
      two groups did not differ in motor evoked potential or latency, nor in the
      excitability of intracortical inhibitory or facilitatory circuits assessed using
      paired stimulation. The acute effect of isocapnic non-invasive ventilation was
      studied in six established ventilator users. Diaphragm motor evoked potential
      fell but there was no effect on intracortical facilitation or inhibition,
      implying an effect of neuromechanical feedback at brainstem or spinal level.

PMID- 22652439
TI  - Active brain targeting of a fluorescent P-gp substrate using polymeric magnetic
      nanocarrier system.
AB  - Magnetic nanoparticles (NP) were developed for the active brain targeting of
      water-soluble P-glycoprotein (P-gp) substrate rhodamine 123 (Rh123). The NP
      matrix of poly(lactide-co-glycolide) (PLGA) and methoxy poly(ethyleneglycol)
      poly(lactic acid) (M-PEG-PLA) was prepared by single emulsion solvent evaporation
      of polymers with oleic acid-coated magnetic nanoparticles (OAMNP) and Rh123. All
      formulations were characterized in terms of morphology, particle size, magnetic
      content and Rh123 encapsulation efficiency. The maximum encapsulation efficiency
      of Rh123 was 45 +/- 3% and of OAMNP was 42 +/- 4%. The brain targeting and
      biodistribution study was performed on Sprague Dawley rats (3 groups, n = 6).
      Rh123 (0.4 mg kg(-1)) was administered in saline form, NP containing Rh123, and
      NP containing Rh123 in the presence of a magnetic field (0.8 T). The fluorimetric
      analysis of brain homogenates revealed a significant uptake (p < 0.05) of Rh123
      in the magnetically targeted group relative to controls. These results were
      supported by fluorescence microscopy. This study reveals the ability of
      magnetically targeted nanoparticles to deliver substances to the brain, the
      permeation of which would otherwise be inhibited by the P-gp system.

PMID- 22652440
TI  - Management of recurrent ankylosis in arthrogryposis: new solutions to a rare
      problem.
AB  - Arthrogryposis is a rare condition that comprises contracture of the joints,
      muscular weakness, and fibrosis. Restricted mouth opening caused by coronoid
      hyperplasia has been reported but to our knowledge, ankylosis of the
      temporomandibular joint (TMJ) has not. Standard management of ankylosis includes
      creation of a gap arthroplasty and possible reconstruction with autogenous or
      alloplastic materials. We describe management of a patient with arthrogryposis
      who developed ankylosis for a second time after satisfactory gap arthroplasty and
      total replacement of the TMJ with a custom-made prosthesis. The original
      prosthesis was removed, the ankylosis resected, and the prosthesis replaced. This
      has given an excellent outcome at 12 months.

PMID- 22652441
TI  - Photocatalytic reduction of Cr(VI) by small molecular weight organic acids over
      schwertmannite.
AB  - In this study, a series of bath experiments was carried out to investigate the
      photoreduction of Cr(VI) by small molecular weight organic acids (SOAs) over
      schwertmannite, a mineral found in acid mine drainage (AMD). The results
      demonstrated that schwertmannite or SOAs alone was unable to effectively
      transform Cr(VI) to Cr(III) even if exposed to an illumination of mimic solar
      light. However, an addition of schwertmannite significantly enhanced the
      reduction of Cr(VI) by SOAs under the same condition. For example, 100MUM Cr(VI)
      was almost completely removed within 50min in the presence of both schwertmannite
      (0.6gL(-1)) and oxalic acid (300MUM) at pH 3.0. The photocatalytic reduction of
      Cr(VI) was strongly influenced by pH, the initial concentrations and the
      structures of SOAs. Of the tested three SOAs, the reaction rates of
      photocatalytic reduction of Cr(VI) were in the order of oxalic acid>citric
      acid>tartaric acid. The reaction obeyed to zero-order kinetics with respect to
      Cr(VI) with excess SOAs. A possible mechanism for photoreduction of Cr(VI) by
      SOAs over schwertmannite was proposed. Fe(III) on the surface of schwertmannite
      was dissolved by SOAs, and then Fe(III)-SOA complexes with high photochemical
      activity formed. Further, Fe(II) together with organic acid radicals, CO(2)(-)
      and O(2)(-), was generated through a metal-ligand-charge-transfer pathway (MLCT),
      leading to a rapid reduction of Cr(VI).

PMID- 22652442
TI  - Roles of ATP-dependent N-acylhomoserine lactones (AHLs) and extracellular
      polymeric substances (EPSs) in aerobic granulation.
AB  - Aerobic granules which form through a cell-to-cell self-immobilization process
      have been intensively studied and developed for wastewater biotreatment. However,
      the microbiological origin of this phenomenon is still largely unknown. This
      study investigated the possible role of metabolic energy in the development of
      aerobic granules. Results showed that aerobic granulation was positively related
      to ATP-dependent N-acylhomoserine lactones (AHLs) and extracellular polymeric
      substances (EPSs) production. Inhibited ATP synthesis by a chemical uncoupler,
      3,3',4',5-tetrachlorosalicylanilide, led to significant reduction of AHLs and
      EPSs production, which in turn prevented aerobic granulation. This study for the
      first time demonstrated the involvement of ATP-dependent AHLs in aerobic
      granulation.

PMID- 22652443
TI  - Effect of variations in the redox potential of Gleysol on barium mobility and
      absorption in rice plants.
AB  - Two assays were designed to obtain information about the influence of redox
      potential variations on barium mobility and bioavailability in soil. One assay
      was undertaken in leaching columns, and the other was conducted in pots
      cultivated with rice (Oryza sativa) using soil samples collected from the surface
      of Gleysol in both assays. Three doses of barium (100,300 mg kg(-1) and 3000 mg
      kg(-1)-soil dry weight) and two redox potential values (oxidizing and reducing)
      were evaluated. During the incubation period, the redox potential (Eh) was
      monitored in columns and pots until values of -250 mV were reached. After the
      incubation period, geochemical partitioning was conducted on the barium using the
      European Communities Bureau of Reference (BCR) method. Rainfall of 200 mm d(-1)
      was simulated in the columns and in the planting of rice seedlings in the pots.
      The results of the geochemical partitioning demonstrated that the condition of
      reduction favors increased barium concentrations in the more labile chemical
      forms and decreased levels in the chemical forms related to oxides. The highest
      barium concentrations in leached extracts (3.36 mg L(-1)) were observed at the
      highest dose and condition of reduction at approximately five times above the
      drinking water standard. The high concentrations of barium in the soil did not
      affect plant dry matter production. The highest levels and accumulation of barium
      in roots, leaves, and grains of rice were found at the highest dose and condition
      of reduction. These results demonstrate that reduction leads to solubilization of
      barium sulfate, thereby favoring greater mobility and bioavailability of this
      element.

PMID- 22652444
TI  - Fabrication, mechanical and in vivo performance of polycaprolactone/tricalcium
      phosphate composite scaffolds.
AB  - This paper explores the use of selective laser sintering (SLS) for the generation
      of bone tissue engineering scaffolds from polycaprolactone (PCL) and
      PCL/tricalcium phosphate (TCP). Different scaffold designs are generated, and
      assessed from the point of view of manufacturability, porosity and mechanical
      performance. Large scaffold specimens are produced, with a preferred design, and
      are assessed through an in vivo study of the critical size bone defect in sheep
      tibia with subsequent microscopic, histological and mechanical evaluation.
      Further explorations are performed to generate scaffolds with increasing TCP
      content. Scaffold fabrication from PCL and PCL/TCP mixtures with up to 50 mass%
      TCP is shown to be possible. With increasing macroporosity the stiffness of the
      scaffolds is seen to drop; however, the stiffness can be increased by minor
      geometrical changes, such as the addition of a cage around the scaffold. In the
      animal study the selected scaffold for implantation did not perform as well as
      the TCP control in terms of new bone formation and the resulting mechanical
      performance of the defect area. A possible cause for this is presented.

PMID- 22652445
TI  - Sixty cases of extreme osteonecrosis and osteomyelitis of the mandible and
      maxilla in a West African population.
AB  - A description of 60 cases of extreme osteonecrosis and osteomyelitis of the jaws
      is presented. The patients attended the dental clinics of the medical charity
      organisation Mercy Ships, over a 2.5-year period when the hospital ship the
      'Africa Mercy' was docked in the West African countries of Liberia, Benin and
      Togo. Possible reasons for the development of these clinical conditions are
      discussed including aetiologies, genetics (coagulopathies, osteopetrosis),
      Gorham's disease, infective conditions (tuberculosis, herpes zoster, HIV
      infection, osteomyelitis), toxicity (bisphosphonates, spider bites), and
      environmental effects (phossy jaw, radium jaw). The possible causes of these
      cases of osteonecrosis and osteomyelitis of the jaw are under investigation.

PMID- 22652446
TI  - Mandible reconstruction with transport-disc distraction osteogenesis in children
      of deciduous dentition.
AB  - Reconstructing segmental mandibular defects in children of deciduous dentition is
      a challenge. The authors treated a 23-month-old girl with a segmental mandibular
      defect secondary to tumour resection. Considering the unpredictable negative
      impacts of the autogenous bone grafting method on the musculoskeletal system of
      the donor sites, which was growing rapidly at this age, the authors applied
      transport disc distraction osteogenesis (TDDO) to reconstruct the mandible
      discontinuity. To the best of the authors' knowledge, this is the first time TDDO
      has been used for mandible reconstruction in such a young patient with deciduous
      dentition. Aesthetics and function were restored satisfactorily at the end of
      treatment. The facial appearance and occlusion were stable through the 35 month
      follow-up, possibly due to the growth of the regenerated bone parallel with the
      rest of the maxillofacial skeleton. The satisfactory reconstruction also
      contributed to the patient's physical and psychological development. The success
      of mandible reconstruction with TDDO in this study casts new light on the
      management of segmental mandibular defect in children with deciduous dentition.

PMID- 22652447
TI  - VEGF expression from human dysplastic or malignant oral epithelium may be related
      to mast cell density and the subsequent angiogenetic phenomena.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic cytokine and mast
      cells play a role in neoangiogenesis in various malignancies. The aim of the
      present study was to elucidate the role of VEGF and mast cells in the early
      stages of tumorigenesis in oral squamous cell carcinoma (OSCC).
      Immunohistochemistry was conducted to study VEGF expression and microvessel
      density (MVD) in 49 tissue samples, 31 OSCCs, 13 leukoplakias (8 with and 5
      without dysplasia) and 5 samples from normal oral tissue. Counterstaining with
      tolouidine blue was conducted to reveal mast cells. The number of microvessels
      and mast cells were counted at the same optical field. A gradually increased VEGF
      expression was observed from normal oral epithelium to leukoplakia and OSCC. MVD
      was found to increase significantly between normal oral tissue and OSCC
      (p=0.000). The number of mast cells was found to increase significantly between
      normal oral tissue, dysplasia (p=0.012) and OSCC (p=0.000). In the early stages
      of tumorigenesis in OSCC, VEGF, which is secreted by the epithelium, is gradually
      increased immediately affecting the population of mast cells, which are then
      related to the increase of microvessels.

PMID- 22652448
TI  - Endocultivation: the influence of delayed vs. simultaneous application of BMP-2
      onto individually formed hydroxyapatite matrices for heterotopic bone induction.
AB  - When bone morphogenetic protein (BMP) is delivered to matrices in vivo may affect
      tissue engineered bone constructs for jaw reconstruction after cancer surgery.
      This study compared the effects of BMP application at different times after
      matrix implantation for heterotopic bone induction in a rat model. Hydroxyapatite
      blocks were implanted unilaterally onto the surface of the latissimus dorsi
      muscle. A second block was implanted onto the contralateral muscle after 1, 2 or
      4 weeks and 200 MUg rhBMP-2 was injected into the blocks on both sides. Bone
      formation and density inside the blocks was analysed by CT and histology. 8 weeks
      after BMP application increases in bone density within the scaffolds were most
      pronounced in the simultaneous application group (179 HU). Less pronounced
      increases were observed for the 1 (65 HU), 2 (58 HU) and 4 (31 HU; p<0.0001) week
      delay group. Homogeneous bone induction started from the central channel of the
      blocks. Capillaries and larger vessels were seen in all constructs, samples
      receiving delayed BMP treatment demonstrated significantly greater
      neovascularization. Delayed application of BMP was less effective for heterotopic
      bone formation than simultaneous application. A central channel allows
      homogeneous bone induction directly from the centre of the blocks.

PMID- 22652449
TI  - Nanosecond pulsed electric fields act as a novel cellular stress that induces
      translational suppression accompanied by eIF2alpha phosphorylation and 4E-BP1
      dephosphorylation.
AB  - Recent advances in electrical engineering enable the generation of ultrashort
      electric fields, namely nanosecond pulsed electric fields (nsPEFs). Contrary to
      conventional electric fields used for DNA electroporation, nsPEFs can directly
      reach intracellular components without membrane destruction. Although nsPEFs are
      now recognized as a unique tool in life sciences, the molecular mechanism of
      nsPEF action remains largely unclear. Here, we present evidence that nsPEFs act
      as a novel cellular stress. Exposure of HeLa S3 cells to nsPEFs quickly induced
      phosphorylation of eIF2alpha, activation of its upstream stress-responsive
      kinases, PERK and GCN2, and translational suppression. Experiments using PERK-
      and GCN2-knockout cells demonstrated dual contribution of PERK and GCN2 to nsPEF
      induced eIF2alpha phosphorylation. Moreover, nsPEF exposure yielded the elevated
      GADD34 expression, which is known to downregulate the phosphorylated eIF2alpha.
      In addition, nsPEF exposure caused a rapid decrease in 4E-BP1 phosphorylation
      irrespective of the PERK/GCN2 status, suggesting participation of both eIF2alpha
      and 4E-BP1 in nsPEF-induced translational suppression. RT-PCR analysis of stress
      inducible genes demonstrated that cellular responses to nsPEFs are distinct from
      those induced by previously known forms of cellular stress. These results provide
      new mechanistic insights into nsPEF action and implicate the therapeutic
      potential of nsPEFs for stress response-associated diseases.

PMID- 22652450
TI  - Tunneling nanotubes: emerging view of their molecular components and formation
      mechanisms.
AB  - Cell-to-cell communication is essential for the development and maintenance of
      multicellular organisms. The tunneling nanotube (TNT) is a recently recognized
      distinct type of intercellular communication device. TNTs are thin protrusions of
      the plasma membrane and allow direct physical connections of the plasma membranes
      between remote cells. The proposed functions for TNTs include the cell-to-cell
      transfer of large cellular structures such as membrane vesicles and organelles,
      as well as signal transduction molecules in a wide variety of cell types.
      Moreover TNT and TNT-related structures are thought to facilitate the
      intercellular spreading of virus and/or pathogenic proteins. Despite their
      contribution to normal cellular functions and importance in pathological
      conditions, virtually nothing is known about the molecular basis for their
      formation. We have recently shown that M-Sec (also called TNFaip2) is a key
      molecule for TNT formation. In cooperation with the RalA small GTPase and the
      exocyst complex, M-Sec can induce the formation of functional TNTs, indicating
      that the remodeling of the actin cytoskeleton and vesicle trafficking are
      involved in M-Sec-mediated TNT formation. Discovery of the role of M-Sec will
      accelerate our understanding of TNTs, both at the molecular and physiological
      levels.

PMID- 22652452
TI  - Heat shock proteins in hematopoietic malignancies.
AB  - Inducible heat shock proteins are molecular chaperones whose expression is
      increased after many different types of stress. They have a protective function
      helping the cell to cope with lethal conditions. Their basal expression is low in
      nonstressed, normal and nontransformed cells. However, in cancer cells and
      particularly in hematological malignancies, they are surprisingly abundant.
      Malignant cells have to rewire their metabolic requirements and therefore have a
      higher need for chaperones. This cancer cell addiction for HSPs is the basis for
      the use of HSP inhibitors in cancer therapy. HSPs have been shown to interact
      with different key apoptotic proteins. As a result, HSPs can essentially block
      the apoptotic pathways at several steps, most of them involving the activation of
      cystein proteases called caspases. Apoptosis and differentiation are
      physiological processes that share many common features, for instance, a
      controlled caspase activation and chromatin condensation are frequently observed.
      It is, therefore, not surprising that HSPs may be implicated in the
      differentiation process. HSPs may determine the fate of the cells by
      orchestrating the decision of apoptosis versus differentiation. This review will
      focus on the role of HSPs in hematological malignancies and the emerging
      therapeutic options that are being either proposed or used to target these
      protective proteins.

PMID- 22652454
TI  - GSK3 inactivation is involved in mitochondrial complex IV defect in transforming
      growth factor (TGF) beta1-induced senescence.
AB  - Transforming growth factor beta1 (TGF beta1) induces Mv1Lu cell senescence by
      persistently producing mitochondrial reactive oxygen species (ROS) through
      decreased complex IV activity. Here, we investigated the molecular mechanism
      underlying the effect of TGF beta1 on mitochondrial complex IV activity. TGF
      beta1 progressively phosphorylated the negative regulatory sites of both glycogen
      synthase kinase 3 (GSK3) alpha and beta, corresponding well to the intracellular
      ROS generation profile. Pre-treatment of N-acetyl cysteine, an antioxidant, did
      not alter this GSK3 phosphorylation (inactivation), whereas pharmacological
      inhibition of GSK3 by SB415286 significantly increased mitochondrial ROS,
      implying that GSK3 phosphorylation is an upstream event of the ROS generation.
      GSK3 inhibition by SB415286 decreased complex IV activity and cellular O(2)
      consumption rate and eventually induced senescence of Mv1Lu cell. Similar results
      were obtained with siRNA-mediated knockdown of GSK3. Moreover, we found that GSK3
      not only exists in cytosol but also in mitochondria of Mv1Lu cell and the
      mitochondrial GSK3 binds complex IV subunit 6b which has no electron carrier and
      is topologically located in the mitochondrial intermembrane space. Involvement of
      subunit 6b in controlling complex IV activity and overall respiration rate was
      proved with siRNA-mediated knockdown of subunit 6b. Finally, TGF beta1 treatment
      decreased the binding of the subunit 6b to GSK3 and subunit 6b phosphorylation.
      Taken together, our results suggest that GSK3 inactivation is importantly
      involved in TGF beta1-induced complex IV defects through decreasing
      phosphorylation of the subunit 6b, thereby contributing to senescence-associated
      mitochondrial ROS generation.

PMID- 22652451
TI  - Mixed lineage kinase 3 is required for matrix metalloproteinase expression and
      invasion in ovarian cancer cells.
AB  - Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase
      (MAP3K) that activates MAPK signaling pathways and regulates cellular responses
      such as proliferation, migration and apoptosis. Here we report high levels of
      total and phospho-MLK3 in ovarian cancer cell lines in comparison to immortalized
      nontumorigenic ovarian epithelial cell lines. Using small interfering RNA (siRNA)
      mediated gene silencing, we determined that MLK3 is required for the invasion of
      SKOV3 and HEY1B ovarian cancer cells. Furthermore, mlk3 silencing substantially
      reduced matrix metalloproteinase (MMP)-1, -2, -9 and -12 gene expression and MMP
      2 and -9 activities in SKOV3 and HEY1B ovarian cancer cells. MMP-1, -2, -9 and-12
      expression, and MLK3-induced activation of MMP-2 and MMP-9 requires both
      extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)
      activities. In addition, inhibition of activator protein-1 (AP-1) reduced MMP-1,
      MMP-9 and MMP-12 gene expression. Collectively, these findings establish MLK3 as
      an important regulator of MMP expression and invasion in ovarian cancer cells.

PMID- 22652453
TI  - Insulin receptor substrate 1 expression enhances the sensitivity of 32D cells to
      chemotherapy-induced cell death.
AB  - The adapters IRS1 and IRS2 link growth factor receptors to downstream signaling
      pathways that regulate proliferation and survival. Both suppress factor
      withdrawal-induced apoptosis and have been implicated in cancer progression.
      However, recent studies suggest IRS1 and IRS2 mediate differential functions in
      cancer pathogenesis. IRS1 promoted breast cancer proliferation, while IRS2
      promoted metastasis. The role of IRS1 and IRS2 in controlling cell responses to
      chemotherapy is unknown. To determine the role of IRS1 and IRS2 in the
      sensitivity of cells to chemotherapy, we treated 32D cells lacking or expressing
      IRS proteins with various concentrations of chemotherapeutic agents. We found
      that expression of IRS1, in contrast to IRS2, enhanced the sensitivity of 32D
      cells to chemotherapy-induced apoptosis. When IRS2 was expressed with IRS1, the
      cells no longer showed enhanced sensitivity. Expression of IRS1 did not alter the
      expression of pro- and anti-apoptotic proteins; however, 32D-IRS1 cells expressed
      higher levels of Annexin A2. In 32D-IRS1 cells, IRS1 and Annexin A2 were both
      located in cytoplasmic and membrane fractions. We also found that IRS1
      coprecipitated with Annexin A2, while IRS2 did not. Decreasing Annexin A2 levels
      reduced 32D-IRS1 cell sensitivity to chemotherapy. These results suggest IRS1
      enhances sensitivity to chemotherapy in part through Annexin A2.

PMID- 22652456
TI  - Parkin co-regulated gene is involved in aggresome formation and autophagy in
      response to proteasomal impairment.
AB  - PArkin Co-Regulated Gene is a gene that shares a bidirectional promoter with the
      Parkinson's disease associated gene parkin. The encoded protein (PACRG) is found
      in Lewy bodies and glial cytoplasmic inclusions, the pathological hallmarks of
      parkinsonian disorders. To investigate the function and regulation of PACRG,
      cells were treated with the proteasomal inhibitor, MG-132. As previously reported
      with parkin, inhibition of the proteasome resulted in the formation of aggresomes
      that contained endogenous PACRG. Increased levels of exogenous PACRG resulted in
      an increase in aggresome formation, and conferred significant resistance to
      aggresome disruption and cell death mediated by microtubule depolymerisation. In
      contrast, shRNA mediated knockdown of PACRG significantly reduced aggresome
      numbers. Elevated levels of PACRG also resulted in increased autophagy, as
      demonstrated by biochemical and quantitative analysis of autophagic vesicles,
      whereas lowered levels of PACRG resulted in reduced autophagy. These results
      suggest a role for PACRG in aggresome formation and establish a further link
      between the UPS and autophagy.

PMID- 22652455
TI  - OX2R activation induces PKC-mediated ERK and CREB phosphorylation.
AB  - Deficiencies in brain orexins and components of mitogen activated protein kinase
      (MAPK) signaling pathway have been reported in either human depression or animal
      model of depression. Brain administration of orexins affects behaviors toward
      improvement of depressive symptoms. However, the documentation of endogenous
      linkage between orexin receptor activation and MAPK signaling pathway remains to
      be insufficient. In this study, we report the effects of orexin 2 receptor (OX2R)
      activation on cell signaling in CHO cells over-expressing OX2R and in mouse
      hypothalamus cell line CLU172. Short-term extracellular signal-regulated kinase
      (ERK) phosphorylation and long-term cyclic adenosine monophosphate (cAMP)
      response element binding protein (CREB) phosphorylation were subsequently
      observed in CHO cells that over-express OX2R while 20 min of ERK phosphorylation
      was significantly detected in mouse adult hypothalamus neuron cell line CLU172.
      Orexin A, which can also activate OX2R, mediated ERK phosphorylation was as the
      same as orexin B in CHO cells. A MAPK inhibitor eliminated ERK phosphorylation
      but not CREB phosphorylation in CHO cells. Also, ERK and CREB phosphorylation was
      not mediated by protein kinase A (PKA) or calmodulin kinase (CaMK). However,
      inhibition of protein kinase C (PKC) by GF 109203X eliminated the phosphorylation
      of ERK and CREB in CHO cells. A significant decrease in ERK and CREB
      phosphorylation was observed with 1 MUM GF 109203X pre-treatment indicating that
      the conventional and novel isoforms of PKC are responsible for CREB
      phosphorylation after OX2R activation. In contrast, ERK phosphorylation induced
      by orexin B in CLU172 cells cannot be inhibited by 1 MUM of protein kinase C
      inhibitor. From above observation we conclude that OX2R activation by orexin B
      induces ERK and CREB phosphorylation and orexin A played the same role as orexin
      B. Several isoforms of PKC may be involved in prolonged CREB phosphorylation.
      Orexin B induced ERK phosphorylation in mouse hypothalamus neuron cells differs
      from CHO cell line and cannot be inhibited by PKC inhibitor GF 109203X. And
      hypothalamus neuron cells may use different downsteam pathway for orexin B
      induced ERK phosphorylation. This result supports findings that orexins might
      have anti-depressive roles.

PMID- 22652458
TI  - Thymosin beta4 promotes the migration of endothelial cells without intracellular
      Ca2+ elevation.
AB  - Numerous studies have demonstrated the effects of Tbeta4 on cell migration,
      proliferation, apoptosis and inflammation after exogenous treatment, but the
      mechanism by which Tbeta4 functions is still unclear. Previously, we demonstrated
      that incubation of endothelial cells with Tbeta4 induced synthesis and secretion
      of various proteins, including plasminogen activator inhibitor type 1 and matrix
      metaloproteinases. We also showed that Tbeta4 interacts with Ku80, which may
      operate as a novel receptor for Tbeta4 and mediates its intracellular activity.
      In this paper, we provide evidence that Tbeta4 induces cellular processes without
      changes in the intracellular Ca(2+) concentration. External treatment of HUVECs
      with Tbeta4 and its mutants deprived of the N-terminal tetrapeptide AcSDKP
      (Tbeta4(AcSDKPT/4A)) or the actin-binding sequence KLKKTET (Tbeta4(KLKKTET/7A))
      resulted in enhanced cell migration and formation of tubular structures in
      Matrigel. Surprisingly, the increased cell motility caused by Tbeta4 was not
      associated with the intracellular Ca(2+) elevation monitored with Fluo-4 NW or
      Fura-2 AM. Therefore, it is unlikely that externally added Tbeta4 induces HUVEC
      migration via the surface membrane receptors known to generate Ca(2+) influx. Our
      data confirm the concept that externally added Tbeta4 must be internalized to
      induce intracellular mechanisms supporting endothelial cell migration.

PMID- 22652459
TI  - Fortuitous birth, convivial baptism and early youth of podosomes.

PMID- 22652457
TI  - The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular
      endothelial growth factor promote tumor growth and angiogenesis in oral squamous
      cell carcinoma.
AB  - Growth and metastasis of solid tumors requires induction of angiogenesis to
      ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing
      transformed cells. Through either mutations, hypoxia generated by cytoreductive
      therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a
      change from an avascular to a neovascular phenotype, a transition mediated by the
      hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular
      endothelial growth factor (VEGF) is one example of a gene whose transcription is
      stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and
      survival by stimulating new blood vessel growth in response to such stresses as
      chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a
      tempting target for neutralizing antibodies in the treatment of advanced
      neoplasms. Emerging evidence has shown that the semaphorins, proteins originally
      associated with control of axonal growth and immunity, are regulated by changes
      in oxygen tension as well and may play a role in tumor-induced angiogenesis.
      Through the use of RNA interference, in vitro and in vivo angiogenesis assays and
      tumor xenograft experiments, we demonstrate that expression of semaphorin 4D
      (SEMA4D), which is under the control of the HIF-family of transcription factors,
      cooperates with VEGF to promote tumor growth and vascularity in oral squamous
      cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D
      function along with VEGF could represent a novel anti-angiogenic therapeutic
      strategy for the treatment of OSCC and other solid tumors.

PMID- 22652460
TI  - Fetal thymus graft prevents age-related hearing loss and up regulation of the IL
      1 receptor type II gene in CD4(+) T cells.
AB  - We found that rejuvenation of the recipient immunity by inoculation of young
      CD4(+) T cells or a fetal thymus graft led to down regulation of the interleukin
      1 receptor type II (IL-1R2) gene in CD4(+) T cells and reduced age-related
      hearing loss and degeneration of the spiral ganglion in SAMP1 mice, a murine
      model of human senescence. Our studies on the relationship between age-related
      systemic immune dysfunctions and neurodegeneration mechanisms open up new avenues
      of treatment of neurosenescence, including presbycusis, for which there is no
      effective therapy.

PMID- 22652461
TI  - Usefulness of neuromonitoring in thyroid surgery.
AB  - INTRODUCTION: Identifying the recurrent laryngeal nerve is the gold standard for
      reducing injury in thyroidectomy. OBJECTIVE: To evaluate the usefulness of
      neuromonitoring in identifying the recurrent laryngeal nerve. METHODS: This was a
      study of 259 recurrent laryngeal nerves at risk during thyroidectomy performed
      with neuromonitoring (group A: 129 nerves) and without neuromonitoring (control
      group B: 130 nerves). RESULTS: The percentage of visually unidentified nerves was
      18% in group A and 20% in group B, with no statistical difference. From the
      moment of non-identification, identification with neuromonitoring was achieved in
      group A in 100% of cases. The difference was statistically significant. The
      positive and negative predictive value of neuromonitoring was 100%. CONCLUSIONS:
      Neuromonitoring helps to identify the recurrent laryngeal nerve and increases the
      security of the surgeon in the technique. It is advisable to perform
      neuromonitoring routinely in thyroid surgery.

PMID- 22652462
TI  - Relative potency of albendazole and its sulfoxide metabolite in two in vitro
      tests for developmental toxicity: the rat whole embryo culture and the mouse
      embryonic stem cell test.
AB  - The benzimidazole carbamate albendazole (ABZ), a potent anthelmintic, is a
      teratogenic compound in rats. At present it is unclear to which degree this
      effect is caused by the parent compound or its major metabolite, albendazole
      sulfoxide (ASO). Both substances were studied separately and in combinations to
      mimic incomplete bioactivation in two in vitro tests: mouse embryonic stem cell
      test (EST) and rat whole embryo culture (WEC). In both assays, ABZ and mixtures
      with ASO induced detrimental effects at lower concentrations compared to ASO
      alone. While ABZ caused half-maximal effects on cardiomyocyte differentiation at
      a mean concentration of 0.26 MUM (EST) and dysmorphogenic development of rat
      embryos at 3.7 MUM (WEC), effective concentrations of ASO were similar in both
      assays (10-13 MUM). By using WEC and EST we demonstrate that ABZ exhibits
      stronger inherent embryotoxic potency although ASO might be the proximate
      teratogen in vivo because of higher plasma concentrations.

PMID- 22652463
TI  - Relative parameter sensitivity in prenatal toxicity studies with substances
      classified as developmental toxicants.
AB  - Developmental toxicity testing according to the globally standardized OECD 414
      protocol is an important basis for decisions on classification and labeling of
      developmental toxicants in the European Union (EU). This test requires relatively
      large animal numbers, given that parental and offspring generations are involved.
      In vitro assay designs and systems biology paradigms are being developed to
      reduce animal use and to improve prediction of human hazard. Such approaches
      could benefit from the long-term experience with animal protocols and more
      specifically from information on the relevance of effects observed in these tests
      for developmental toxicity. Therefore, we have analyzed relative parameter
      sensitivity in 22 publicly available developmental toxicity studies, representing
      about one third of all classified developmental toxicants under European
      legislation. Maternal and fetal weight effects and fetal survival were most often
      affected parameters at the developmental Lowest Observed Adverse Effect Level
      (dLOAEL), followed by skeletal malformations. Specific end points such as cleft
      palate were observed in fewer studies at dLOAEL, but if observed may have been
      crucial in classification and labeling decisions. These results are similar to
      earlier studies using different selections of chemicals, indicating that in
      general classified developmental toxicants have a similar pattern of effects at
      the dLOAEL as chemicals in general. These findings are discussed within the
      perspective of the development of innovative alternative approaches to
      developmental hazard assessment.

PMID- 22652464
TI  - Fine structure analysis and sintering properties of Si-doped hydroxyapatite.
AB  - Si-doped hydroxyapatite (Si-HA) has been intensively investigated as a promising
      bone biomaterial because of the biomineralization and bone formation benefit from
      silicon addition. In the current work, Si-HA samples were synthesized by the
      aqueous precipitation method. The sintering property of Si-HA was studied in
      terms of phase composition and transition, which was influenced by the Si doping
      percentage and sintering temperature. The results indicate that all the as
      prepared and sintered low Si doping samples (Si% <= 1.6 wt%) possess HA phases;
      while the high Si doping samples (Si% >= 2 wt%) present amorphous phases as
      prepared, and largely or even completely transform to beta-tricalcium phosphate
      (beta-TCP) phase after sintering at 1250  degrees C. The Rietveld refinement on x
      ray diffraction patterns was conducted to determine the particle sizes,
      microstrain factors and anisotropic distributions. According to the refined
      results, the calculated anisotropic particle sizes correspond to the observations
      made by transmission electron microscopy. The microstrains also present
      anisotropic distributions in all refinements. The accurate variation in the fine
      structure of Si-HA has been studied by the improved refinements after considering
      the anisotropic distribution.

PMID- 22652466
TI  - Intact limbic-prefrontal connections and reduced amygdala volumes in Parkinson's
      disease with mild depressive symptoms.
AB  - BACKGROUND: Depression is very common in Parkinson's disease (PD). The
      neuropathological basis for this remains unclear; however, dysfunction in
      prefrontal and limbic regions may play a role. METHODS: We examined non-demented
      PD patients with and without depression and healthy controls (n = 6 per group)
      for differences in limbic structures and connections between these structures and
      the prefrontal cortex. Depressed individuals were selected from a representative
      sample of 33 PD patients using scores from the 15 question geriatric depression
      scale (GDS). Magnetic resonance diffusion tensor imaging (DTI) tractography was
      used to examine the structural integrity of the uncinate fasciculus (UF), a white
      matter tract that projects from the hippocampus, amygdala and temporal pole to
      the orbitofrontal cortex, and the corpus callosum. Integrity of the UF and corpus
      callosum was established through measures of mean diffusivity (MD), fractional
      anisotropy (FA) and tract length. A volumetric analysis of the hippocampal head,
      body and tail, as well as the amygdala was performed to determine whether volume
      differences in these structures in PD relate to depression. RESULTS: The
      depressed PD group showed smaller amygdala volumes compared to healthy controls,
      but the groups did not differ on any other measure. CONCLUSIONS: The present
      study found intact limbic connectivity but suggests that amygdala atrophy may be
      present in Parkinson's disease with depression. Further work is needed to
      replicate these findings.

PMID- 22652465
TI  - Subcellular distribution of THAP1 and alterations in the microstructure of brain
      white matter in DYT6 dystonia.
AB  - BACKGROUND: Mutations in the THAP1 gene have recently been identified as the
      cause of DYT6 primary dystonia. However, the changes in THAP1 gene function and
      in the microstructure of brain white matter have not been well-characterized.
      METHODS: Four different mutations of THAP1 expression (clones F22fs71X, C54F,
      F25fs53X, and L180S) were transfected into HEK-293T cells. The subcellular
      distribution of THAP1 in each clone was identified using immunofluorescence
      microscopy and Western blot. Six patients who harbored these THAP1 mutations
      underwent diffusion tensor magnetic resonance imaging (DTI) of the brain. The
      fractional anisotropy (FA) and mean diffusivity (MD) were measured in twenty-four
      regions of interest (ROI). RESULTS: In two truncated mutations (F22fs71X and
      F25fs53X), the subcellular distribution of THAP1 were both in the cytoplasm and
      nucleus. However, the subcellular distribution was detected almost in the nucleus
      in two missense mutations (C54F and L180S). In the DTI maps, the average values
      of fractional anisotropy (FA), a measure of axonal integrity and coherence, was
      reduced (p < 0.005) in the subgyral white matter of the sensorimotor cortex of
      the DYT1 carriers, comparing with controls. CONCLUSIONS: Truncated THAP1
      mutations (F22fs71X and F25fs53X) can alter the subcellular distributions, while
      some missense mutation (C54F and L180S) can not. The axonal integrity and
      coherence in the region of sensorimotor area of the brain was damaged in DYT6
      dystonia.

PMID- 22652467
TI  - Adjuvant clinical effects of polydeoxyribonucleotide in lichen sclerosus.

PMID- 22652468
TI  - Recombinant human granulocyte-macrophage colony-stimulating factor hydrogel
      promotes healing of deep partial thickness burn wounds.
AB  - OBJECTIVE: To assess the effects of recombinant human granulocyte/macrophage
      colony-stimulating factor (rhGM-CSF) hydrogel on the healing of deep partial
      thickness burn wounds. METHODS: Ninety three wounds of 65 burn patients who
      suffered from a deep partial thickness burn of <5% TBSA and could not heal over 3
      weeks were included in this study. The patients were randomly assigned to use
      rhGM-CSF hydrogel (GC group, n=32) or hydrogel without rhGM-CSF (control group,
      n=33). rhGM-CSF hydrogel or hydrogel without rhGM-CSF was topically applied to
      the wounds, the dressing was changed once a day. Wound healing time and
      percentage, wound discharge, periwound inflammation, the positive wound swabs
      culture count, and adverse drug reactions were observed and compared between two
      groups. RESULTS: Healing time was 12.2 +/- 5.0 days after the application of rhGM
      CSF hydrogel. This was significantly shorter than that of control wounds (15.5 +/
      4.7 days). Healing percentage at 14 days in the rhGM-CSF-treated wounds was 97.5
      +/- 7.7%, which was markedly higher than the control (85.9 +/- 6.8%). At 3, 6,
      12, 14 day, the GC group was significantly superior to the control group with
      respect to the score of periwound inflammation, wound purulence and discharge.
      The positive wound swabs culture count of the GC group on the 7th and 14th day
      post-treatment was 14 and 4, respectively, which was significantly lower than the
      control. CONCLUSION: rhGM-CSF hydrogel promotes the healing process of deep
      partial thickness burns effectively. No adverse reaction of the drug was observed
      during the study.

PMID- 22652469
TI  - Urinary excretion of histamine and methylhistamine after burns.
AB  - BACKGROUND: The increased vascular permeability seen after burn contribute to
      morbidity and mortality as it interferes with organ function and the healing
      process. Large efforts have been made to explore underlying pathophysiological
      mechanisms that generate increased vascular permeability after burns. Many
      different substances have been proposed as mediators of which histamine,
      serotonin and oxygen radicals are claimed most important. However, no specific
      blocker has convincingly been shown to be clinically effective. Early work has
      claimed increased histamine plasma-concentrations in humans after burn and data
      from animal models pointed at histamine as an important mediator. Modern human
      clinical studies investigating the role of histamine as a mediator of the
      generalized post burn increase in vascular permeability are lacking. METHOD: We
      examined histamine turnover by measuring the urinary excretion of histamine and
      methyl histamine for 48 h after burns in 8 patients (mean total burn surface area
      24%). RESULTS: Over time, in this time frame and compared to healthy controls we
      found a small increase in the excretion of histamine, but no increase of its
      metabolite methylhistamine. CONCLUSION: Our findings do not support that
      histamine is an important mediator of the increased systemic vascular
      permeability seen after burn.

PMID- 22652471
TI  - Non-traumatic subluxation of the atlantoaxial joint after thermal burn of the
      head and the neck. Case report.

PMID- 22652472
TI  - Early management of eyelid burns with full-thickness skin grafts prevents eye
      injury.

PMID- 22652473
TI  - Comparison of five dermal substitutes in full-thickness skin wound healing in a
      porcine model.
AB  - The wound healing attributes of five acellular dermal skin substitutes were
      compared, in a two-step procedure, in a porcine model. Ten pigs were included in
      this experimental and randomized study. During the first step, dermal substitutes
      (Integra((r)), ProDerm((r)), Renoskin((r)), Matriderm((r)) 2mm and
      Hyalomatrix((r)) PA) were implanted into full-thickness skin wounds and the
      epidermis was reconstructed during a second step procedure at day 21 using
      autologous split-thickness skin graft or cultured epithelial autograft. Seven
      pigs were followed-up for 2 months and 3 pigs for 6 months. Dermal substitute
      incorporation, epidermal graft takes, wound contraction and Vancouver scale were
      assessed, and histological study of the wounds was performed. Results showed
      significant differences between groups in dermis incorporation and in early wound
      contraction, but there was no difference in wound contraction and in Vancouver
      scale after 2 and 6 months of healing. We conclude there was no long-term
      difference of scar qualities in our study between the different artificial
      dermis. More, there was no difference between artificial dermis and the control
      group. This study makes us ask questions about the benefit of artificial dermis
      used in a two-step procedure.

PMID- 22652474
TI  - A simple technique for the retrieval of buried staples.
AB  - The use of staples for skin graft fixation is practiced in many burn centers
      worldwide. This application provides a fast and easy means of fixation. However,
      buried staples are frequently encountered if the staples are forgotten or removed
      too late. Apart from physical symptoms, buried staples can also lead to potential
      medico-legal consequences. In our center, we adopt a simple retrieval technique
      for the buried staples with the assistance of C-arm image intensifier. This
      method allows quick identification and removal of buried staples while minimizing
      tissue disruption. We describe this technique in the following article.

PMID- 22652475
TI  - Comments on "Sympathetic skin response in electrical burn injury".

PMID- 22652476
TI  - A pilot evaluation study of high resolution digital thermal imaging in the
      assessment of burn depth.
AB  - Thermal imaging is a tool that can be used to determine burn depth. We have
      revisited the use of this technology in the assessment of burns and aim to
      establish if high resolution, real-time technology can be practically used in
      conjunction with clinical examination to determine burn depth. 11 patients with
      burns affecting upper and lower limbs and the anterior and posterior trunk were
      included in this study. Digital and thermal images were recorded at between 42 h
      and 5 days post burn. When compared to skin temperature, full thickness burns
      were significantly cooler (p<0.001), as were deep partial thickness burns
      (p<0.05). Superficial partial thickness burns were not significantly different in
      temperature than non-burnt skin (p>0.05). Typically, full thickness burns were
      2.3 degrees C cooler than non-burnt skin; deep partial thickness burns were 1.2
      degrees C cooler than non-burnt skin; whilst superficial burns were only 0.1
      degrees C cooler. Thermal imaging can correctly determine difference in burn
      depth. The thermal camera produces images of high resolution and is quick and
      easy to use.

PMID- 22652477
TI  - The domestication of fire: the relationship between biomass fuel, fossil fuel and
      burns.
AB  - Primitive man's discovery and use of fire had a tremendous impact on modern
      development. It changed lifestyles, and brought with it new fuel sources and
      cooking methods. It also introduced devastation, injury, pain, disfigurement, and
      loss of life, and the need to continuously develop management, training and
      prevention programs.

PMID- 22652478
TI  - VACUETTE((r)) for burn depth assessment--a simple and novel alternative use for a
      ubiquitous phlebotomy device.
AB  - The depth of any burn wound is an important determinant of its management and
      outcome. It also governs the outcome of wound healing and scarring making initial
      depth assessment extremely vital. Various methods both invasive and non-invasive
      have been described in literature for burn depth estimation. We describe a useful
      adjunct to clinical burn depth assessment, a VACUETTE((r)) venous blood sampling
      device. This single cheap, ubiquitous and sterile device usually used for
      phlebotomy allows subjective assessment of the most useful parameters in the
      assessment of burn wounds, including, capillary refill, evaluation of sensation
      to blunt and sharp stimuli including pain.

PMID- 22652479
TI  - Burns and use of mirror to prevent these injuries among young and adult workers
      at hot clay ovens, tandoors: an innovative, cost-effective solution in a low
      income setting.

PMID- 22652480
TI  - Reproductive experiences of teenagers in the Ejisu-Juabeng district of Ghana.
AB  - OBJECTIVE: To determine the proportions of male and female teenagers aged 15-19
      years who have ever been involved in pregnancy, and to examine factors associated
      with involvement in teenage pregnancy in the Ejisu-Juabeng district of Ghana.
      METHODS: In a household-based cross-sectional survey, 481 randomly selected male
      and female teenagers were enrolled between August 3 and September 17, 2009. Study
      variables included demographics; sexual exposure; contraceptive use; and
      involvement in pregnancy, childbirth, and induced abortion. Multivariable
      multinomial logistic regression analyses were used to examine the association
      between involvement in pregnancy, and the background and reproductive profiles of
      the respondents via SPSS version 16.0. RESULTS: Both the mean and median ages of
      the respondents were 17.2 years. One-third of respondents lived with both
      parents, and one-third lived with single mothers. The median age of sexual debut
      was 16.0 years. Approximately 58% of sexually experienced females had been
      pregnant, and 37% had had an induced abortion. Age at sexual debut, gender, and
      being out of school were significantly associated with involvement in teenage
      pregnancy, whereas residential status, relationship with first partner, and
      contraceptive use were not. CONCLUSION: Keeping adolescents enrolled in school
      might reduce their risk of involvement in pregnancy in the Ejisu-Juabeng district
      of Ghana.

PMID- 22652481
TI  - Value and feasibility of LLETZ procedures for pregnant women with suspected high
      grade squamous intraepithelial lesions and microinvasive cervical cancer.
AB  - OBJECTIVE: To evaluate the efficacy, safety, and feasibility of large loop
      excision of the transformation zone (LLETZ) procedures during pregnancy. METHODS:
      A retrospective study included 27 patients who underwent LLETZ during pregnancy
      for suspected high-grade squamous intraepithelial lesions (HSIL) where
      microinvasion could not be excluded. The study investigated intraoperative and
      postoperative complications, and compared preoperative and postoperative results.
      Questionnaires were used to obtain information about peripartum and postpartum
      data. RESULTS: Three (11.1%) women had invasive or microinvasive cancer, 22
      (81.5%) had cervical intraepithelial neoplasia (CIN) 3, and 1 (3.7%) had CIN 2.
      Twenty-four were positive for high-risk human papillomavirus. All cervical
      cancers were classified as HSIL or CIN 3 before LLETZ. There were positive
      resection margins in 15 (55.6%) cases. No intraoperative complications occurred.
      One (3.7%) patient had a postoperative missed abortion. Major complications such
      as premature labor or cervical incompetence without influence on delivery
      occurred after LLETZ in 4 (14.8%) patients. CONCLUSION: LLETZ during pregnancy
      can be performed if invasive cancer cannot be excluded by colposcopy, cytology,
      or biopsy. The procedure has a diagnostic intention but can also be a curative
      therapy in pregnancy, with low intraoperative, postoperative, and peripartum
      complication rates.

PMID- 22652482
TI  - Comparison of PET/CT with other imaging modalities in women with genital
      tuberculosis.
AB  - OBJECTIVE: To compare findings with 2-deoxy-2-((18)F)fluoro-D-glucose positron
      emission tomography combined with computed tomography ((18)F-FDG-PET/CT) with
      findings obtained using ultrasound (US), magnetic resonance imaging (MRI), and CT
      in patients with proven tubercular tubo-ovarian masses. METHODS: Seventeen
      patients with proven tubercular tubo-ovarian masses underwent (18)F-FDG-PET/CT
      imaging and the findings were compared with US (for all patients), MRI (for 9
      patients), CT (for 4 patients), and laparotomy or laparoscopic findings (for 14
      patients). RESULTS: Eleven patients (64.7%) had unilateral tubo-ovarian masses,
      with activity in 6 masses (35.3%); 4 patients (23.5%) had bilateral tubo-ovarian
      masses, with activity in all masses; and 2 patients (11.76%) had unilateral space
      occupying lesions, with activity in 1 lesion. The detection rates of tubo-ovarian
      masses with (18)F-FDG-PET/CT were similar to, but the characterization of adnexal
      masses was less than, those obtained with CT or MRI. Finally, (18)F-FDG-PET/CT
      was equally accurate as laparoscopy or laparotomy in detecting the presence,
      laterality, and activity of tubo-ovarian masses. CONCLUSION: Imaging with (18)F
      FDG-PET/CT is noninvasive and appears to be clinically useful for the diagnosis
      of tubercular tubo-ovarian masses.

PMID- 22652483
TI  - Optogenetic activation during detector "dead time" enables compatible real-time
      fluorescence imaging.
AB  - Optogenetic tools, such as channelrhodopsin2 (ChR2), have enabled the behavior of
      whole organisms by light-mediated manipulation of neuronal activities.
      Fluorescent indicators have been used to aid in the understanding of what is
      happening in living cells. To date, optogenetic stimulation and imaging
      acquisition were sequentially performed during detector "live time." However,
      there is a problem with interrupting acquisition time sequences because such
      stimulation invades the time territory of fluorescent imaging. Here, our purpose
      was to show that optogenetic stimulation can be performed within the "dead time"
      of the charge-coupled device camera, the short interval of data transfer between
      frames. We show the kinetic measurement of Ca(2+) dynamics in neuron-like cells
      upon ChR2 stimulation, by which we reveal the biphasic property of the Ca(2+)
      increase in response to optical stimulation.

PMID- 22652484
TI  - Functionalized polymer spheres via one-step photoinduced synthesis for
      antimicrobial activity and gene delivery.
AB  - Despite the fact that polystyrene (PS) spheres have been developed as polymeric
      carriers or matrices for various biomedical applications, the synthesis of PS
      spheres is time-consuming. This work describes the fabrication of a uniform PS
      sphere, coated with silver nanoparticles (Ag-PS), by simultaneous photoinduced
      polymerization and reduction fabricated using x-rays in aqueous solution without
      any initiator. The solution contains only styrene, silver ions (Ag(+)), and
      poly(vinyl pyrrolidone) (PVP) as a stabilizer. The proposed mechanism of the
      formation of the Ag-PS nanocomposite spheres involves the generation of radicals
      in the aqueous solution to induce PS polymerization and the reduction of Ag. The
      distribution of the sizes of the core PS spheres in the Ag-PS nanocomposite
      spheres was systematically examined as a function of irradiation time,
      concentration of styrene, and amount of PVP. Ag-PS nanocomposite spheres exhibit
      antimicrobial activity against bacteria (Escherichia coli and Staphylococcus
      aureus). Additionally, the cationic (vinylbenzyl)trimethylammonium (TMA) monomer
      was photopolymerized to form positively charged TMA-PS spheres as gene carriers
      with uniquely low cytotoxicity. Given these design advantages, the method
      proposed herein is simpler than typical approaches for synthesizing PS spheres
      with functionalized groups and PS spheres coated with Ag nanoparticles.

PMID- 22652485
TI  - Velopharyngeal and choanal stenosis after radiotherapy for nasopharyngeal
      carcinoma.
AB  - Choanal stenosis is a well recognized late complication of radiotherapy for
      nasopharyngeal carcinoma. However velopharyngeal stenosis post radiotherapy for
      nasopharyngeal carcinoma is rare. We present here a case of bilateral choanal
      stenosis and velopharyngeal stenosis in a patient treated with radiotherapy for
      nasopharyngeal carcinoma. A 58-year-old woman presented to our otolaryngology
      clinic with a one year history of nasal obstruction. She was diagnosed to have
      nasopharyngeal carcinoma 12 years ago for which she received radiotherapy.
      Clinical examination revealed bilateral choanal stenosis and velopharyngeal
      stenosis. Treatment of choanal stenosis and velopharyngeal stenosis is
      challenging due to high incidence of recurrence and patients frequently require
      multiple procedures. The patient underwent a transnasal endoscopic excision of
      velopharyngeal scar tissue and widening of posterior choana using Surgitron(r),
      mitomycin-C applied topically to the surgical wound and bilateral stenting under
      general anesthesia. The stents were kept for two weeks, and 3 years post
      operation velopharyngeal aperture and posterior choana remained patent. As
      illustrated in this case velopharyngeal stenosis can occur after radiotheraphy
      and should not be overlooked. Combine modality of transnasal endoscopic excision
      of velopharyngeal scar tissue, widening of choanal stenosis with Surgitron(r)
      followed by the application of mitomycin-C and stenting has been shown to be an
      effective option.

PMID- 22652486
TI  - A cohort study of patients with tinnitus and sensorineural hearing loss in a
      Swedish population.
AB  - OBJECTIVE: We aimed to describe a large cohort of patients with tinnitus and
      sensorineural hearing loss (SNHL) in Sweden, and also to explore the possibility
      of finding potential possible differences between various diagnoses within SNHL.
      It is also of great interest to see how a multidisciplinary team was used in the
      different subgroups and the frequency of hearing aids use in patients with
      tinnitus. METHODS: Medical records of all patients who had received the diagnosis
      SNHL in Ostergotland County, Sweden between 2004 and 2007 were reviewed. Patients
      between 20 and 80 years with tinnitus and a pure tone average (PTA) lower than
      70dB HL were included in the study. Patients were excluded from the analyses if
      they had a cochlear implantation, middle ear disorders or had a hearing loss
      since birth or childhood. The investigators completed a form for each included
      patient, covering background facts, and audiograms taken at the yearly check up.
      RESULTS: Of a total 1672 patients' medical record review, 714 patients were
      included. The majority of patients (79%) were in the age group over 50 years. In
      male patients with bilateral tinnitus, the PTA for the left ear was significantly
      higher than for the right ear. The results regarding the configuration of hearing
      loss revealed that 555 patients (78%) had symmetric and 159 (22%) asymmetric
      hearing loss. Retrocochlear examinations were done in 372 patients and MRI was
      the most common examination. In all patients, 400 had no hearing aids and out of
      those 220 had unilateral tinnitus and 180 patients had bilateral tinnitus. 219
      patients had a PTA>20dB HL and did not have any hearing aid. Results demonstrated
      that the Stepped Care model was not used widely in the daily practice. In our
      study, patients with bilateral-, unilateral hearing loss or Mb Meniere were the
      most common patients included in the Stepped Care model. CONCLUSION: In a large
      cohort of patients with SNHL and tinnitus, despite their hearing loss only 39%
      had hearing aids. It was observed that the medical record review often showed a
      lack of information about many background factors, such as; patients' general
      health condition, which could be a quality factor that needs improvement. Our
      results show that the Stepped Care model could be an effective option for
      providing a better access for tinnitus-focused treatment, although the number of
      patients in this study who were included in the Stepped Care model was low.

PMID- 22652487
TI  - Factors affecting the use of emergency obstetric care among pregnant women with
      antenatal bleeding.
AB  - OBJECTIVE: to investigate the factors that affect the use of emergency obstetric
      care services among pregnant women in Turkey with antenatal bleeding. DESIGN:
      descriptive, cross-sectional study. SETTING: Mersin Maternity and Child Hospital,
      Mersin, Turkey. PARTICIPANTS: 125 pregnant women who had been admitted to the
      emergency department for antenatal bleeding. FINDINGS: advanced age, high level
      of education, lack of health insurance, receiving antenatal care, nuclear family
      structure and knowledge of the danger signs during pregnancy were found to affect
      the use of emergency obstetric care services among pregnant women with antenatal
      bleeding. KEY CONCLUSIONS: delays in seeking emergency obstetric care among
      pregnant women with antenatal bleeding are due to the difficulties faced by women
      when deciding whether or not to seek health care. Access to health services and
      health institutions themselves do not cause any delay in terms of provision of
      emergency obstetric care to pregnant women with antenatal bleeding. IMPLICATIONS
      FOR PRACTICE: pregnant women should be informed about the causes of antenatal
      bleeding, what to do in the case of bleeding, and the need to seek health care as
      soon as possible. In addition, midwives should inform families and pregnant women
      about the use of emergency medical services and the relevant procedures.

PMID- 22652488
TI  - A novel capture compound for the identification and analysis of cyclic di-GMP
      binding proteins.
AB  - The second messenger cyclic di-GMP is a near-ubiquitous signaling molecule that
      globally alters bacterial cell physiology to promote biofilm formation and
      community behavior. Much progress was made in recent years towards the
      identification and characterization of diguanylate cyclases and
      phosphodiersterases, enzymes involved in the synthesis and degradation of this
      signaling compound. In contrast, our knowledge of the nature and mechanistic
      details of c-di-GMP effector proteins lags behind, primarily because effective
      tools for their specific enrichment and rapid analysis are missing. In this
      report we demonstrate that a novel tri-functional c-di-GMP-specific Capture
      Compound (cdG-CC) can be effectively used to identify and validate c-di-GMP
      binding proteins. The cdG-CC was able to specifically and efficiently pull down
      bona fide c-di-GMP effector proteins. Furthermore, in combination with mass
      spectrometry (CCMS), this technology robustly identified a substantial fraction
      of the known c-di-GMP signaling components directly from cell extracts of
      different model organisms. Finally, we applied the CCMS technique to profile c-di
      GMP binding proteins of Pseudomonas aeruginosa and Salmonella enterica serovar
      typhimurium. Our studies establish CCMS as a powerful and versatile tool to
      identify and analyze components of the cellular c-di-GMP pathway in a wide range
      of different organisms.

PMID- 22652489
TI  - Proteomic study of beta-aminobutyric acid-mediated cadmium stress alleviation in
      soybean.
AB  - The present study highlights the protective role of beta-aminobutyric acid (BABA)
      in alleviating cadmium (Cd) stress in soybean. Proteomic analyses revealed that
      out of 66 differentially abundant protein spots in response to Cd challenge, 17
      were common in the leaves of BABA-primed and non-primed plants. Oxygen-evolving
      enhancer protein 1 and ribulose bisphosphate carboxylase small chain 1 were
      detected in increase abundance in both groups of leaves. Among the 15 commonly
      decreased protein spots, the relative intensity levels of heat shock cognate 70
      kDa protein, carbonic anhydrase, methionine synthase, and glycine dehydrogenase
      were partially restored after BABA treatment. Moreover, BABA priming
      significantly enhanced the abundance of the defense-related protein peroxiredoxin
      and glycolytic enzymes in response to Cd exposure. Additionally, the impact of Cd
      on the physiological state of BABA-primed and non-primed plants was analyzed
      using a biophoton technique. The finding of comparatively low biophoton emission
      in BABA-primed leaves under Cd stress indicates that these plants experienced
      less oxidative damage than that of non-primed plants. Proteomic study coupled
      with biophoton analysis reveals that BABA pretreatment helps the plants to combat
      Cd stress by modulating plants' defence mechanism as well as activating cellular
      detoxification system to protect the cells from Cd induced oxidative stress
      damages.

PMID- 22652490
TI  - Identification and profiling of salinity stress-responsive proteins in Sorghum
      bicolor seedlings.
AB  - Sorghum bicolor, a drought tolerant cereal crop, is not only an important food
      source in the semi arid/arid regions but also a potential model for studying and
      gaining a better understanding of the molecular mechanisms of drought and salt
      stress tolerance in cereals. In this study, seeds of a sweet sorghum variety,
      MN1618, were planted and grown on solid MS growth medium with or without 100mM
      NaCl. Heat shock protein expression immunoblotting assays demonstrated that this
      salt treatment induced stress within natural physiological parameters for our
      experimental material. 2D PAGE in combination with MS/MS proteomics techniques
      were used to separate, visualise and identify salinity stress responsive proteins
      in young sorghum leaves. Out of 281 Coomassie stainable spots, 118 showed
      statistically significant responses (p<0.05) to salt stress treatments. Of the
      118 spots, 79 were selected for tandem mass spectrometric identification, owing
      to their good resolution and abundance levels, and of these, 55 were positively
      identified. Identified proteins were divided into six functional categories
      including both known and novel/putative stress responsive proteins. Molecular and
      physiological functions of some of our proteins of interest are currently under
      investigation via bioinformatic and molecular biology approaches.

PMID- 22652491
TI  - New postcranial fossils of Australopithecus afarensis from Hadar, Ethiopia (1990
      2007).
AB  - Renewed fieldwork at Hadar, Ethiopia, from 1990 to 2007, by a team based at the
      Institute of Human Origins, Arizona State University, resulted in the recovery of
      49 new postcranial fossils attributed to Australopithecus afarensis. These
      fossils include elements from both the upper and lower limbs as well as the axial
      skeleton, and increase the sample size of previously known elements for A.
      afarensis. The expanded Hadar sample provides evidence of multiple new
      individuals that are intermediate in size between the smallest and largest
      individuals previously documented, and so support the hypothesis that a single
      dimorphic species is represented. Consideration of the functional anatomy of the
      new fossils supports the hypothesis that no functional or behavioral differences
      need to be invoked to explain the morphological variation between large and small
      A. afarensis individuals. Several specimens provide important new data about this
      species, including new vertebrae supporting the hypothesis that A. afarensis may
      have had a more human-like thoracic form than previously appreciated, with an
      invaginated thoracic vertebral column. A distal pollical phalanx confirms the
      presence of a human-like flexor pollicis longus muscle in A. afarensis. The new
      fossils include the first complete fourth metatarsal known for A. afarensis. This
      specimen exhibits the dorsoplantarly expanded base, axial torsion and domed head
      typical of humans, revealing the presence of human-like permanent longitudinal
      and transverse arches and extension of the metatarsophalangeal joints as in human
      like heel-off during gait. The new Hadar postcranial fossils provide a more
      complete picture of postcranial functional anatomy, and individual and temporal
      variation within this sample. They provide the basis for further in-depth
      analyses of the behavioral and evolutionary significance of A. afarensis anatomy,
      and greater insight into the biology and evolution of these early hominins.

PMID- 22652492
TI  - Fine resolution of early hominin time, Beds I and II, Olduvai Gorge, Tanzania.
AB  - Reconstructing paleoenvironments and landscapes within lake-centered, hominin
      yielding basinal sequences requires a resolution of time-rock units finer than
      but complementary to that provided by the present tephrostratigraphy. Although
      indispensable in providing an absolute time frame at Olduvai, the average 15,000
      20,000 year intervals between successive tuff units lack the time resolution to
      construct a sufficiently contemporary paleolandscape within sedimentary intervals
      away from the interleaved tuffs. Such control is essential to construct valid
      paleogeographies in which to contextualize contemporaneous paleoanthropological
      sites and the traces of hominin land use they contain. Within Beds I and II of
      the Olduvai Basin a Sequence Stratigraphic analysis has achieved a relative time
      framework in which time-rock units, "lake-parasequences," each generated by a
      major advance and withdrawal of the lake system, are recognizable for average
      periods of about 4000 years duration. Within each of these time slices at least
      two paleogeographic landscapes are identifiable, reducing the time constraints of
      an individual landscape reconstruction to a few thousand years. Within the
      sedimentary succession both highly incised and less incised unconformities are
      identifiable to provide sequence boundaries. Within each sequence the higher
      frequency lake-parasequences can be identified by (1) a disconformable base, (2)
      accretion of sediment during lake transgression and at maximum, (3) a
      disconformable top caused by lake withdrawal, and (4) a soil profile generated
      beneath that disconformable land surface. Individual lake-parasequences can be
      recognized in lake marginal and fan settings, and their imprint can also be seen
      in the lake setting where, for example, maximum flooding might be marked by a
      layer of dolomite. Lower Bed II parasequences represent time intervals of <5000
      years, while parasequential periods between Tuffs IB and IC in Bed I are <4300
      years. Analogous Holocene lake-level changes of the same order in East Africa
      have a period close to 4200 years. The estimated period is close to that defined
      by Stadial/Interstadial Dansgaard-Oeschger Events recorded in the Greenland Ice
      record, which force cycles of period similar to lake-parasequences, both in the
      Arabian Sea and Lake Malawi. Lake-parasequences not only aid construction of
      landscapes, they also allow contextualization of individual paleoanthropological
      occurrences. For instance, a parasequence lies between Leakey's Level 1 and her
      butchered Deinotherium occurrence at FLK N. However, elephantid and giraffid
      skeletons associated with stone artifacts at VEK, uncovered by OLAPP excavations,
      are situated on the same land surface as a possibly butchered rhinocerid at KK.
      To complement the existing absolute radiometric time framework, relative Sequence
      Stratigraphic techniques might be applied to any lake-centered, hominin-yielding
      basinal sequence, not only those found within East Africa. Because they are
      climatically controlled, and might plausibly be related to globally driven
      Dansgaard-Oeschger Events, lake-parasequences and their associated sequences
      might be correlatable between various East African basins in the Plio-Pleistocene
      in the same way as they presently are for the Holocene.

PMID- 22652493
TI  - Prediabetic increase in hemoglobin A1c compared with impaired fasting glucose in
      patients receiving antipsychotic drugs.
AB  - BACKGROUND: In 2010, the American Diabetes Association recommended that
      individuals with hemoglobin A1c 5.7-6.4% be classified as prediabetic even in the
      absence of impaired fasting glucose (IFG). AIM OF STUDY: To compare the clinical
      and metabolic characteristics of patients receiving antipsychotic drugs who have
      normal glucose tolerance (NGT), hemoglobin A1c 5.7-6.4% or IFG (fasting glucose
      100-125 mg/dL). METHOD: Body mass index, waist circumference, fasting glucose,
      insulin, lipids, hemoglobin A1c, and insulin resistance assessed with the
      homeostatic model (HOMA-IR) were measured in a consecutive cohort of adult
      psychiatric inpatients with NGT (N = 423), hemoglobin A1c 5.7-6.4% (N = 130), IFG
      (N = 52) and IFG plus hemoglobin A1c 5.7-6.4% (n = 39). RESULTS: The hemoglobin
      A1c 5.7-6.4% group had lower fasting insulin levels (9.8 +/- 5.6 vs. 15.5 +/-
      11.4 MUU/mL, p < 0.0001) and HOMA-IR (2.1 +/- 1.2 vs. 4.1 +/- 3.1, p < 0.0001)
      than the IFG group, but were metabolically similar to those with NGT. The
      hemoglobin A1c 5.7-6.4% was the predominant prediabetic pattern in patients
      treated with antipsychotics other than clozapine or olanzapine. Patients with
      hemoglobin A1c 5.7-6.4% and those with IFG were statistically similar in age
      (40.1 +/- 13.6 vs. 39.7 +/- 10.3 years), body mass index (26.0 +/- 4.8 vs. 26.3
      +/- 4.9) and waist circumference 93.1 +/- 13.9 vs. 98.1 +/- 12.1 cm for males and
      92.5 +/- 13.5 vs. 90.7 +/- 15.8 cm for females. CONCLUSION: The hemoglobin A1c in
      the 5.7-6.4% range is common in euglycemic patients receiving antipsychotic drugs
      and this prediabetic pattern has metabolic and pharmacological features that
      differentiates it from IFG.

PMID- 22652495
TI  - A self-assembled Ag nanoparticle agglomeration process on graphene for enhanced
      light output in GaN-based LEDs.
AB  - We introduce Ag nanoparticles fabricated by a self-assembled agglomeration
      process in order to enhance the electrical properties, adhesive strength, and
      reliability of the graphene spreading layer in inorganic-based optoelectronic
      devices. Here, we fabricated InGaN/GaN multi-quantum-well (MQW) blue LEDs having
      various current spreading layers: graphene only,  graphene with Ag nanoparticles
      covering the surface, and graphene with Ag nanoparticles only in selectively
      patterned micro-circles. Although the Ag nanoparticles were found to act as an
      additional current path that increases the current spreading, optical properties
      such as transmittance also need to be considered when the Ag nanoparticles are
      combined with graphene. As a result, LEDs having a graphene spreading layer with
      Ag nanoparticles formed in selectively patterned micro-circles displayed more
      uniform and stable light emission and 1.7 times higher light output power than
      graphene only LEDs.

PMID- 22652494
TI  - Tako-Tsubo cardiomyopathy caused immediately following cesarean section delivery
      of triplets: a case report.
AB  - The name 'tako-tsubo' cardiomyopathy was initially used to describe a unique
      'short-neck round-flask'-shaped form of left ventricular apical ballooning,
      resembling a Japanese tako-tsubo, a jar (tsubo) used for capturing octopus
      (tako). Tako-tsubo cardiomyopathy exhibits acute onset, transient left
      ventricular apical wall motion abnormalities with chest symptoms and minimal
      myocardial enzymatic release, mimicking acute myocardial infarction in patients
      without angiographic stenosis on coronary angiography. There have been few case
      reports on tako-tsubo cardiomyopathy, and this disorder is especially rare in
      pregnant women. A 30-year-old woman who was pregnant with triplets, and had been
      treated with ritodrine hydrochloride for 12 weeks for threatened premature
      delivery, underwent cesarean section with spinal anesthesia at 30 weeks'
      gestation. Three hours later, she complained of acute chest pain, dyspnea and
      episodes of unconsciousness. She was transferred to the intensive care unit and
      intubated for ventilatory support. We diagnosed heart failure due to tako-tsubo
      cardiomyopathy based on heart ultrasonography, blood tests, chest X-ray,
      electrocardiogram and myocardial scintigraphy. She was extubated from the
      ventilator after 3 days of catecholamine, furosemide and carperitide
      administration. She was discharged from the hospital on day 53 without symptoms.

PMID- 22652496
TI  - Staphylococcus aureus and Staphylococcus epidermidis adhesion to
      nanohydroxyapatite in the presence of model proteins.
AB  - Bacterial infections can have adverse effects on the efficacy, lifetime, and
      safety of an implanted device. The aim of this study was to investigate the
      initial adhesion of several strains, namely S. aureus and S. epidermidis, on two
      distinct types of nanohydroxyapatite (nanoHA), sintered at 725  degrees C and
      1000  degrees C. A comparison was also made with nanohydroxyapatite having
      adsorbed fetal bovine serum (FBS), human fibronectin (FN) and human serum albumin
      (HSA). Adhered bacterial cells were examined by scanning electron microscopy and
      quantified as colony forming units after being released by sonication. The
      wettability of the sample surface with and without adsorbed protein was assessed
      by contact-angle measurements. NanoHA sintered at 1000  degrees C showed lower
      bacterial adhesion than this heat-treated at 725  degrees C. Adsorption of FBS
      onto the nanoHA surface caused a decrease in the adhesion of all strains on both
      materials. The bacterial adhesion patterns in the presence of FN were different
      for both nanoHA substrates; the adherence of the bacterial strains, except for
      the clinical strain of S. epidermidis, was significantly higher on nanoHA 1000 in
      comparison to nanoHA 1000 without protein and the bacterial adhesion on the FN
      coated nanoHA 725 was lower in comparison to the bare nanoHA 725. The effect of
      HSA on bacterial adhesion was concentration and bacterial strain dependent.

PMID- 22652497
TI  - Prevalence and associated socio-demographic factors of chronic suppurative otitis
      media among rural primary school children of Bangladesh.
AB  - BACKGROUND: Chronic suppurative otitis media (CSOM) is a common community health
      disorder of childhood in all developing countries including Bangladesh. In
      children, it may cause significant delays in speech, cognitive, educational and
      psychological development. OBJECTIVES: To determine prevalence of CSOM and its
      relationship with certain socio-demographic factors among rural primary school
      going children of Bangladesh. METHODOLOGY: 4280 rural primary school children of
      palash upazilla of Narsingdi district, Bangladesh had underwent ENT check up by
      doctors trained in ENT and their guardians were interviewed regarding certain
      socio demographic factors using a pre tested protocol. RESULTS: 48% of them were
      boys and 52% were girls with a mean age of 8.8 years (SD+/-2.35). 5.63% of study
      population revealed to have CSOM and girls were relatively more sufferer than
      boys (6.6% vs 4.5%). Our study revealed statistically significant association of
      CSOM with age, sex, guardian's income, maternal education, family size, and
      sanitation of children. Housing though an important risk factor of CSOM but it
      was not evident in this study. CONCLUSION: Thus, improvement of the socio
      demographic status and primary ear care education to children, their teachers and
      guardians can prevent these vulnerable children from developing CSOM and
      resultant complications.

PMID- 22652498
TI  - Effects of rapid maxillary expansion on middle ear function: one-year follow-up.
AB  - OBJECTIVE: To evaluate the effects of rapid maxillary expansion (RME) on middle
      ear function before, after, 3 months and one year from expansion procedure.
      PATIENTS AND METHODS: Eighteen patients with mean age of 8.1 years (+/-3.7) and
      posterior cross-bite were followed from pre expansion to one year after RME,
      regarding their hearing quality and middle ear function. Nine of them presented
      middle ear dysfunction (MED) and nine presented normal function (NF) before rapid
      maxillary expansion. Audiometric and tympanometric exams were taken before rapid
      maxillary expansion, after RME (15 days), 3 months and one year after rapid
      maxillary expansion. RESULTS: Among those in the MED group, no patient had
      acoustic reflex (AR) before rapid maxillary expansion; 67% presented type C
      tympanometric curve, 22% had type A and 11% had As type tympanometric curve. One
      year after rapid maxillary expansion, all patients presented AR and showed type A
      tympanometric curves. In NF group, all patients showed AR and type A
      tympanometric curves in all records. In both groups no audiograms presented
      significant variations along study. CONCLUSION: Rapid maxillary expansion has no
      deleterious effect in hearing quality and seems to improve middle ear function in
      children with posterior cross-bite in a one-year perspective.

PMID- 22652500
TI  - Successful treatment of two invasive squamous cell carcinomas with topical 5%
      imiquimod cream in elderly patients.

PMID- 22652499
TI  - Cochlear implanted children present vocal parameters within normal standards.
AB  - OBJECTIVE: to compare acoustic and perceptual parameters regarding the voice of
      cochlear implanted children, with normal hearing children. METHOD: this is a
      cross-sectional, quantitative and qualitative study. METHODS: Thirty six cochlear
      implanted children aged between 3 y and 3 m to 5 y and 9 m and 25 children with
      normal hearing, aged between 3 y and 11 m and 6 y and 6 m, participated in this
      study. The recordings and the acoustics analysis of the sustained vowel/a/and
      spontaneous speech were performed using the PRAAT program. The parameters
      analyzed for the sustained vowel were the mean of the fundamental frequency,
      jitter, shimmer and harmonic-to-noise ratio (HNR). For the spontaneous speech,
      the minimum and maximum frequencies and the number of semitones were extracted.
      The perceptual analysis of the speech material was analyzed using visual
      analogical scales of 100 points, composing the aspects related to the overall
      severity of the vocal deviation, roughness, breathiness, strain, pitch, loudness
      and resonance deviation, and instability. This last parameter was only analyzed
      for the sustained vowel. RESULTS: The results demonstrated that the majority of
      the vocal parameters analyzed in the samples of the implanted children disclosed
      values similar to those obtained by the group of children with normal hearing.
      CONCLUSION: implanted children who participate in a (re) habilitation and follow
      up program, can present vocal characteristics similar to those vocal
      characteristics of children with normal hearing.

PMID- 22652501
TI  - Mechanical analysis of cuff tear arthropathy during multiplanar elevation with
      the AnyBody shoulder model.
AB  - BACKGROUND: This numerical study analysed the mechanics of cuff tear arthropathy
      with the AnyBody shoulder model. METHODS: The model simulated three frequent
      characteristics of cuff tear arthropathy: A supero-posterior massive rotator cuff
      tear, a proximal and static migration of the humeral head, and a contact between
      the humeral head and the scapula (glenoid & acromion) with friction. The
      mechanics of the cuff tear arthropathy with and without friction were studied by
      analysing: the mechanics of the deltoid (i.e. length & strength), the gleno
      humeral and acromio-humeral contact forces, the friction moment, and the maximum
      elevation angle. Elevations in the frontal, scapular and sagittal planes were
      simulated. FINDINGS: Compared to an intact condition, the cuff tear arthropathy
      model without friction estimated a deltoid strength of -18% (frontal=-13%,
      scapular=-17%, sagittal=-25%), a gleno-humeral contact force of -34% (frontal=
      60%, scapular=-46%, sagittal=+5%), estimated an acromio-humeral contact force of
      240 N (frontal=213 N, scapular=184 N, sagittal=324 N) and a maximum elevation
      angle of 77 degrees  (frontal=80 degrees , scapular=87 degrees , sagittal=65
      degrees ). Contact friction enhanced this behaviour, decreasing even more the
      gleno-humeral contact force and the maximum elevation angle, while increasing the
      acromio-humeral contact force. INTERPRETATION: This novel cuff tear arthropathy
      model suggests that friction and plane of elevation greatly influence the
      mechanics of the shoulder with cuff tear arthropathy. It also shows that the
      AnyBody simulation tool may be useful to study musculoskeletal pathologies and
      not only normal conditions.

PMID- 22652502
TI  - The effect of experimental shortening of the clavicle on shoulder kinematics.
AB  - BACKGROUND: Malunion after mid shaft clavicle fractures has recently been
      recognized as a cause of pain and dysfunction of the shoulder. The mechanism that
      causes these complaints is however yet unclear. In this study we describe the
      kinematic changes that occur in the shoulder girdle due to clavicle shortening.
      METHODS: An experimental cadaveric study was performed on five shoulders of three
      fresh frozen specimens. The specimens were fixed in an upright position that
      allowed free motion of the shoulder girdle. We measured position of the bony
      structures with an opto-electronic system (Northern Digital Inc., Waterloo,
      Ontario Canada) in rest and during in a series of motions. Measurements were done
      with a normal clavicle and after shortening of the clavicle by 1.2, 2.4 and 3.6
      cm. The shoulders were moved manually by one of the researchers. We examined for
      changes in resting position and during movement that resulted from the
      experimental shortening of the clavicle. FINDINGS: In the resting position,
      winging of the scapula increased with resultant changes in the orientation of the
      glenoid, acromio-clavicular and sterno-clavicular joints and an altered position
      of the clavicle. On average protraction increased by 20 degrees , lateral
      rotation changed 12 degrees  and posterior tilt decreased by 7 degrees . Clavicle
      shortening affected sterno-clavicular joint rotations but did not do so in the
      acromio-clavicular joint. In arm elevation the offset in scapula orientation at
      resting position stayed relatively constant over the full range of motion but the
      amount of disposition is progressive in relation to the amount of shortening.
      INTERPRETATION: Shortening of the clavicle leads to significant changes in the
      shoulder girdle in resting position and in movement.

PMID- 22652503
TI  - Precalcaneal congenital fibrolipomatous hamartoma.

PMID- 22652504
TI  - Chronic plantar ulcer in an immigrant from Africa.

PMID- 22652505
TI  - Sweet-like lesions induced by bortezomib: a review of the literature and a report
      of 2 cases.

PMID- 22652506
TI  - Macular carotenoid supplementation in subjects with atypical spatial profiles of
      macular pigment.
AB  - This study was designed to investigate the impact of macular carotenoid
      supplementation on the spatial profile of macular pigment (MP) in subjects where
      the profile does not exhibit the typical central peak (i.e. peaked MP at foveal
      epicentre). Thirty one healthy subjects with such atypical MP spatial profiles
      were assigned to one of three intervention groups: Group 1: (n = 10), 20 mg/day
      lutein (L), 2 mg/day zeaxanthin (Z); Group 2: (n = 10), 10 mg/day meso-zeaxanthin
      (MZ), 10 mg/day L, 2 mg/day Z; Group 3: (n = 10), 17 mg/day MZ, 3 mg/day L, 2
      mg/day Z. Subjects were instructed to take one capsule daily over an 8-week
      period. MP at 0.25 degrees , 0.5 degrees , 1 degrees , 1.75 degrees  and 3
      degrees  was measured using customized-heterochromatic flicker photometry at
      baseline, four weeks and 8 weeks. Over the study period, we report no
      statistically significant increase in MP at any eccentricity in Group 1 (p >
      0.05, for all eccentricities). There was a trend towards an increase in MP at all
      eccentricities in Group 2, with a significant increase found at 0.25 degrees  and
      0.50 degrees  (p = 0.000 and p = 0.016, respectively). There was a statistically
      significant increase evident in MP at 0.25 degrees  in Group 3 (p = 0.005), but
      at no other eccentricity (p > 0.05, for all other). We report that the typical
      central peak of MP can be realised in subjects with atypical spatial profiles,
      following supplementation with a preparation containing all three macular
      carotenoids, but not with a supplement lacking MZ. The implications of our
      findings, in terms of visual performance and/or a (photo)-protective effect,
      warrant additional study.

PMID- 22652507
TI  - The way of sex: Joseph Needham and Jolan Chang.
AB  - This paper analyses the understandings of Daoist alchemy and Chinese sexuality of
      Joseph Needham and his friend and correspondent, the Chinese-Swedish writer Jolan
      Chang (Chang Chung-lan, 1917-2002). Using the extensive correspondence between
      the two men, as well as Needham's files on "inner alchemy" deposited at the
      Needham Research Institute, the paper begins with a partial reconstruction of a
      1977 symposium, chaired by Needham, to promote Chang's new book, The Tao of Love
      and Sex: The Ancient Chinese Way to Ecstasy. Needham and Chang's visions of
      Chinese sex are then read against excerpts from Science and Civilisation in
      China, specifically Volume V: Chemistry and Chemical Technology, Part 5:
      Spagyrical Discovery and Invention: Physiological Alchemy (1983). Three inter
      related aspects are explored. First, reading Science and Civilisation in China
      against materials in the Needham archives offers crucial hints to Needham's
      historiography and historical practice. Second, the way that Daoist regimens came
      to be actively reconstructed and repackaged as practices concerned with the
      enhancement of sexual pleasure and intensity. Third, the investigation of the
      networks and circulations of assumptions, visions, fantasies about "China".

PMID- 22652508
TI  - Facile and rapid synthesis of spherical porous palladium nanostructures with high
      catalytic activity for formic acid electro-oxidation.
AB  - Highly uniform, spherical porous palladium nanostructures (SPPNs) with rough
      surfaces were prepared by a facile and rapid ultrasound assisted reduction. The
      synthesis involves sonicating a solution of K(2)PdCl(4) and ascorbic acid for
      only 7 min at 40  degrees C without any additives. The products are isolated
      structures with a narrow size distribution, and their average diameters are
      controllable in a range from 40 to 100 nm via the K(2)PdCl(4) concentration.
      Typical products have a diameter of 52 nm and consist of loosely packed grains of
      2-3 nm. They are thus very porous, with a specific surface area of 47 m(2) g(-1).
      The growth mechanism of SPPNs is discussed on the basis of varying relevant
      reaction parameters and characterizations from different microscopy techniques,
      nitrogen absorption analysis, and time-dependent UV-vis spectra. The
      electrocatalytic performance of the SPPNs was evaluated by electro-oxidation of
      formic acid. The mass current density per mass of SPPNs (1.88 A mg(-1)) exceeds
      that of commercial Pd black (1.69 A mg(-1)) and is more than twice that of
      commercial Pd/C catalyst (0.79 A mg(-1)). Long-term stability of the activity
      makes this material a promising anode catalyst for direct formic acid fuel cells.

PMID- 22652509
TI  - Core protein-mediated 5'-3' annealing of the West Nile virus genomic RNA in
      vitro.
AB  - Genome cyclization through conserved RNA sequences located in the 5' and 3'
      terminal regions of flavivirus genomic RNA is essential for virus replication.
      Although the role of various cis-acting RNA elements in panhandle formation is
      well characterized, almost nothing is known about the potential contribution of
      protein cofactors to viral RNA cyclization. Proteins with nucleic acid chaperone
      activities are encoded by many viruses (e.g., retroviruses, coronaviruses) to
      facilitate RNA structural rearrangements and RNA-RNA interactions during the
      viral replicative cycle. Since the core protein of flaviviruses is also endowed
      with potent RNA chaperone activities, we decided to examine the effect of West
      Nile virus (WNV) core on 5'-3' genomic RNA annealing in vitro. Core protein
      binding resulted in a dramatic, dose-dependent increase in 5'-3' complex
      formation. Mutations introduced in either the UAR (upstream AUG region) or CS
      (conserved sequence) elements of the viral RNA diminished core protein-dependent
      annealing, while compensatory mutations restored the 5'-3' RNA interaction. The
      activity responsible for stimulating RNA annealing was mapped to the C-terminal
      RNA-binding region of WNV core protein. These results indicate that core protein 
      besides its function in viral particle formation - might be involved in the
      regulation of flavivirus genomic RNA cyclization, and thus virus replication.

PMID- 22652510
TI  - Population-environment drivers of H5N1 avian influenza molecular change in
      Vietnam.
AB  - This study identifies population and environment drivers of genetic change in
      H5N1 avian influenza viruses (AIV) in Vietnam using a landscape genetics
      approach. While prior work has examined how combinations of local-level
      environmental variables influence H5N1 occurrence, this research expands the
      analysis to the complex genetic characteristics of H5N1 viruses. A dataset of 125
      highly pathogenic H5N1 AIV isolated in Vietnam from 2003 to 2007 is used to
      explore which population and environment variables are correlated with increased
      genetic change among viruses. Results from non-parametric multidimensional
      scaling and regression analyses indicate that variables relating to both the
      environmental and social ecology of humans and birds in Vietnam interact to
      affect the genetic character of viruses. These findings suggest that it is a
      combination of suitable environments for species mixing, the presence of high
      numbers of potential hosts, and in particular the temporal characteristics of
      viral occurrence, that drive genetic change among H5N1 AIV in Vietnam.

PMID- 22652511
TI  - The relationship between cluster-analysis derived walkability and local
      recreational and transportation walking among Canadian adults.
AB  - We investigated the association between objectively-assessed neighborhood
      walkability and local walking among adults. Two independent random cross
      sectional samples of Calgary (Canada) residents were recruited. Neighborhood
      based walking, attitude towards walking, neighborhood self-selection, and socio
      demographic characteristics were captured. Built environmental attributes
      underwent a two-staged cluster analysis which identified three neighborhood types
      (HW: high walkable; MW: medium walkable; LW: low walkable). Adjusting for all
      other characteristics, MW (OR 1.40, p < 0.05) and HW (OR 1.34, approached p <
      0.05) neighborhood residents were more likely than LW neighborhood residents to
      participate in neighborhood-based transportation walking. HW neighborhood
      residents spent 30-min/wk more on neighborhood-based transportation walking than
      both LW and MW neighborhood residents. MW neighborhood residents spent 14-min/wk
      more on neighborhood-based recreational walking than LW neighborhood residents.
      Neighborhoods with a highly connected pedestrian network, large mix of
      businesses, high population density, high access to sidewalks and pathways, and
      many bus stops support local walking.

PMID- 22652512
TI  - Phylogeographical structure of the tick Ixodes persulcatus: a novel view.
AB  - The tick Ixodes persulcatus Schulze, 1930, has a wide distribution from the
      Baltic to the Far East and is a vector of a number of human pathogens. Thus, the
      study of the genetic structure and evolution of this species is of great
      epidemiological importance. rRNA genes were used as genetic markers to identify
      the phylogeographical structure of the ticks. The sequences of gene fragments of
      28S (expansion segment D3) and mitochondrial 12S rRNA for 25 and 76 ticks,
      respectively, that had been collected in various regions of Russia in 2007-2011,
      were obtained. The sequences of the 28S rRNA D3 segment were identical for all
      ticks within the studied area. Analysis of the sequences of the mitochondrial 12S
      rRNA fragment revealed 4 haplotypes with one occurring at a frequency of 0.96. It
      is shown that the 'deep' population structure of I. persulcatus (McLain et al.,
      2001) was erroneous because of the inclusion of contaminating fungi sequences of
      28S rRNA in the phylogenetic analysis. This was, possibly, due to the use of
      universal PCR primers that amplify the DNA of a wide range of eukaryotes,
      particularly of fungi which are common in samples of ticks. The influence of PCR
      conditions on the preferential amplification of the DNA of different organisms is
      also demonstrated.

PMID- 22652514
TI  - [Left hemiparesis with headache in a 4-year-old boy. Unilateral closed-lip
      schizencephaly].

PMID- 22652513
TI  - Skin temperature responses to cold stress in patients with severe motor and
      intellectual disabilities.
AB  - Patients with severe motor and intellectual disabilities (SMID) often suffer from
      autonomic nervous system disturbances. At the same time, the caregivers of
      patients with SMID face challenges to understand the patients' chronic health
      problems effectively by simply observing them. Therefore, recognizing specific
      symptoms is important to improve support for SMID. We investigated the autonomic
      nervous function in patients with SMID with skin vasomotor responses to cold
      stimuli. The relationship of the results of cold stress and autonomic symptoms
      observed by the main caretakers was also examined. We analyzed 38 patients with
      SMID. Their hand skin temperature was measured before and after cold stimuli
      using infrared thermography. A 'distal-dorsal difference' (DDD) at baseline, and
      the recovery rate of the second fingertip and dorsum were calculated. All main
      caregivers filled out questionnaires evaluating autonomic symptoms. The recovery
      rate of the second fingertip and dorsum after cold stimuli was lower than 80% in
      64% and 60% patients, respectively. The baseline DDD was greater than 1  degrees
      C in 84% of the patients. A DDD>1  degrees C was associated with a reduced
      recovery rate. All caregivers recognized some autonomic-related symptoms.
      Patients with constipation or snoring demonstrated a reduced recovery rate.
      However, none of the observed symptoms can predict the presence of a reduced rate
      with cold stimuli in a statistically significant way. This study showed excessive
      sympathetic nerve activities in patients with SMID. The baseline DDD could be a
      valuable parameter accessing their microvascular circulation. To improve the life
      of a person with SMID, accessing autonomic function using a noninvasive method,
      such as thermography is warranted without directly observed symptoms.

PMID- 22652515
TI  - [Systematic review and meta-analysis: simple knowledge overview or original
      research tool?].

PMID- 22652516
TI  - [Acute cannabis poisoning in a 10-month-old infant].
AB  - We describe a case of accidental cannabis poisoning in a 10-month-old girl, who
      presented with impaired consciousness, with drowsiness and restlessness,
      generalized hypotonia, and inadequate smiles. No circulatory or respiratory
      problems were observed. Initial investigations were not informative (blood
      biology, CT scan, and cerebrospinal fluid examination), while the main causes of
      coma (meningoencephalitis, head trauma, metabolic disorders) were excluded.
      Questioning the parents led to suspecting accidental ingestion of a piece of
      cannabis, which was confirmed by the detection of high blood and urine levels of
      cannabinoid derivatives. Management was symptomatic and the clinical course,
      marked by the occurrence of agitation and irritability episodes lasting up to
      H18, led to complete regression of symptoms. Because of the high consumption in
      France, pediatric poisoning by cannabis seems increasingly common. The toxic
      levels in children are unknown however. Diagnosis is based on questioning and the
      search for cannabinoid derivatives in urine. In children, clinical symptoms are
      more expressive compared to adults, with neurological (drowsiness, agitation,
      abnormal behavior, ataxia, hypotonia, coma, and convulsions) or cardiopulmonary
      (tachycardia, bradypnea, apnea) or homeostatic presentations (hypothermia).
      Treatment in children is essentially symptomatic but sometimes requires active
      resuscitation. Recommendations are based on clinical monitoring the first 24h
      after intoxication and on medicosocial support.

PMID- 22652517
TI  - [Severe tetanus complicated with rhabdomyolysis and acute renal failure: a
      pediatric case report].
AB  - Renal failure is a rare complication of tetanus in children. It occurs following
      poorly controlled muscle spasms and rigidity. We describe a severe case of
      tetanus complicated with rhabdomyolysis and acute renal failure in a child.

PMID- 22652518
TI  - [Early onset pediatric sarcoidosis, diagnostic problems].
AB  - Sarcoidosis, a chronic multisystem inflammatory granulomatous disorder of unknown
      origin, is a rare disease in children. Two distinct clinical presentations of
      sarcoidosis in childhood are known. Older children usually show multisystem
      disease, close to the adult manifestation, with lung infiltration and frequent
      hilar lymphadenopathy. Prior to the age of 5, sarcoidosis reveals more frequently
      with the classical triad of rash, arthritis, and uveitis. Due to non-specific
      clinical features and the lack of a specific test, recognizing sarcoidosis can be
      difficult in the pediatric population. Moreover, unlike in adults, lung
      involvement is rare in pediatric sarcoidosis. Given the lack of a definitive
      blood test, the World Association of Sarcoidosis and Other Granulomatous
      disorders (WASOG) only recommends dosing the serum angiotensin-converting enzyme
      (ACE). Its level is usually higher in children than in adults, but an increased
      ACE may help in the diagnosis. The gold standard is a biopsy specimen with
      typical epithelioid gigantocellular granuloma without caseating necrosis
      granuloma, after other disorders known to cause granulomatous disease have been
      reasonably excluded. We report here the case of a 4.5-year-old male with the
      history of polyarthritis and uveitis, considered first as juvenile rheumatoid
      arthritis, followed 5 years later by cutaneous involvement, which led to
      reconsidering the diagnosis. There were no pulmonary clinical findings. Histology
      provided the diagnosis of sarcoidosis. He then developed dependence on steroids.
      The lack of the classical triad delayed the diagnosis several years. This case
      shows the pediatric singularity of sarcoidosis, which needs to be known so that
      early and appropriate follow-up can be conducted.

PMID- 22652519
TI  - [Bronchiolitis among infants under 1 year of age in France: epidemiology and
      factors associated with mortality].
AB  - Little information is available on the characteristics of infants hospitalized
      for acute bronchiolitis in France. An analysis of hospital records (PMSI) was
      conducted at the national level to describe the cases of bronchiolitis that
      require hospitalization among infants under 1 year of age and the factors
      associated with death. The analysis of all admissions that occurred during 2009,
      for which the diagnosis of acute bronchiolitis was recorded in the PMSI database
      for infants aged less than 1 year, was performed. Cases were described according
      to age, sex, underlying conditions (including bronchopulmonary dysplasia, cystic
      fibrosis, and congenital heart disease), length of hospital stay, recurrent
      admissions, admission to an intensive care unit (ICU), and use of assisted
      ventilation. Factors associated with death during hospitalization were studied by
      logistic regression. The hospitalization rate was 35.8 per 1000 infants under 1
      year in 2009 in France. Approximately 10% of hospitalized infants required ICU
      admission. Twenty-two infants died. The estimated case-fatality rate was 0.08%
      among hospitalized infants and 0.56% for those hospitalized in the ICU. Mortality
      among all infants under 1 year was 2.6/10(5) in France. Factors associated with
      death were bronchopulmonary dysplasia (OR=6.7, 95% CI [1.5-29.8]),
      hospitalization in an ICU (OR=6.46, 95% CI [2.4-17.4]), and the use of assisted
      ventilation (OR=6.2, 95% CI [2.2-17.1]). This study has enabled the
      quantification of the rate of hospitalization and mortality, and a better
      description of infants who need hospitalization. The results are consistent with
      international literature, but further prospective analysis will be needed to
      better describe the cases at higher risk, aiming to improve their management.

PMID- 22652521
TI  - [Intravenous immunoglobulin-resistant Kawasaki disease with hemophagocytosis].
AB  - Kawasaki disease is acute self-limited vasculitis of unknown etiology that mainly
      affects infants and young children. Many different clinical aspects can be
      encountered. A single dose of intravenous immunoglobulin and treatment by aspirin
      are the standard therapy. Cases of immunoglobulin therapy resistance pose a real
      problem. We report on the case of a 14-year-old boy with Kawasaki disease and
      hemophagocytic syndrome, resistant to the combination of two doses of
      immunoglobulins and three doses of corticosteroids. Recovery was obtained with
      one dose of infliximab. This observation highlights Kawasaki disease in
      adolescents and the therapeutic difficulties that may be encountered in cases of
      resistance to immunoglobulins. Association with macrophage activation syndrome is
      rare.

PMID- 22652522
TI  - Community-associated Panton-Valentine leukocidin-negative meticillin-resistant
      Staphylococcus aureus clone (ST72-MRSA-IV) causing healthcare-associated
      pneumonia and surgical site infection in Korea.
AB  - BACKGROUND: Community-associated meticillin-resistant Staphylococcus aureus (CA
      MRSA) has emerged as an important pathogen worldwide in a continent-specific
      manner. Clinical characteristics of infections caused by CA-MRSA other than
      USA300, especially in healthcare settings, have not been well established. AIM:
      To conduct a retrospective cohort study to determine the clinical characteristics
      of infections caused by Panton-Valentine leukocidin (PVL)-negative, multilocus
      sequence type (ST) 72 staphylococcal cassette chromosome mec (SCCmec) type IV, a
      major CA-MRSA clone in Korea. METHODS: ST72-IV isolates, which were susceptible
      to fluoroquinolones, gentamicin, rifampicin, and cotrimoxazole, were
      presumptively identified among 4667 MRSA isolates and then confirmed by SCCmec
      typing and multilocus sequence typing. A total of 124 cases of ST72-IV infections
      were analysed. FINDINGS: The annual incidence of infections by ST72-IV per
      100,000 admissions increased from 45.5 to 66.3 cases during 2007-2009. The most
      frequently occurring type of infection was skin and soft tissue infection (SSTI)
      (46.0%), followed by pneumonia (27.4%) and bone and joint infection (9.7%).
      Surgical site infection accounted for 22.6% and 32.5% of community-onset (CO)
      healthcare-associated infection and hospital-onset (HO) infection, respectively.
      Pneumonia was most frequent (45.0%) among HO infection. Multivariate analysis
      showed that pneumonia increased the odds of all-cause mortality (odds ratio:
      18.8; 95% confidence interval: 2.6-133.9) compared with other types of infection.
      CONCLUSIONS: Increasing trends were observed in annual incidence of CO and HO
      infections by ST72-IV in Korea. Pneumonia was the most frequent among HO
      infection and was associated with higher mortality. These findings pose important
      implications for successful antibiotic therapy and infection control in the era
      of CA-MRSA.

PMID- 22652524
TI  - Efficient spin filter based on FeN4 complexes between carbon nanotube electrodes.
AB  - We present a theoretical study to explore the spin transport properties of FeN(4)
      complexes sandwiched between two armchair (5, 5) carbon nanotube (CNT)
      electrodes. The ab initio modeling is performed by combining the spin-dependent
      density functional theory with nonequilibrium Green's function formalism. The
      calculated results clearly demonstrate that the transport properties of FeN(4)
      complexes are sensitive to the contact configuration. Near the Fermi level the
      conductance through three examined junctions is mainly governed by the spin-up
      electrons. The FeN(4) complex coupled to CNT electrodes with the pi-type contact
      conjugation can act as a nearly perfect spin filter, and its spin filter
      efficiency is up to 98.0%. Our theoretical results demonstrate that FeN(4)
      complexes are promising for future molecular spintronics devices.

PMID- 22652523
TI  - Memory ability and hippocampal volume in adolescents with prenatal drug exposure.
AB  - The objective of the present study was to examine the influence of prenatal drug
      exposure (PDE) on memory performance and supporting brain structures (i.e.,
      hippocampus) during adolescence. To achieve this goal, declarative memory ability
      and hippocampal volume were examined in a well-characterized sample of 138
      adolescents (76 with a history of PDE and 62 from a non-exposed comparison group
      recruited from the same community, mean age=14 years). Analyses were adjusted
      for: age at time of the assessments, gender, IQ, prenatal exposure to alcohol and
      tobacco, and indices of early childhood environment (i.e., caregiver depression,
      potential for child abuse, and number of caregiver changes through 7 years of
      age). Results revealed that adolescents with a history of PDE performed worse on
      the California Verbal Learning Test-Child Version (CVLT-C), and story recall from
      the Children's Memory Scale (CMS), and had larger hippocampal volumes, even after
      covariate adjustment. Hippocampal volume was negatively correlated with memory
      performance on the CVLT-C, with lower memory scores associated with larger
      volumes. These findings provide support for long-term effects of PDE on memory
      function and point to neural mechanisms that may underlie these outcomes.

PMID- 22652525
TI  - Differentiation of interstitial cells of Cajal in the human distal colon.
AB  - At the end of the embryonic period of human development, interstitial cells of
      Cajal (ICC) are present in the esophagus, stomach, and proximal duodenum, around
      the inception of the myenteric plexus (MP) ganglia. In the small and large bowel,
      ICC appear later. The object of the present study was to determine the timing of
      appearance and pattern of distribution of ICC in the human embryonic and fetal
      distal colon. Human distal colon specimens were obtained from 8 embryos and 14
      fetuses without gastrointestinal disorders. The specimens were 7-16 weeks of
      gestational age. The specimens were exposed to anti-c-kit antibodies to
      investigate ICC differentiation. Enteric plexuses were immunohistochemically
      examined using anti-neuron-specific enolase, and the differentiation of smooth
      muscle cells was studied with anti-desmin antibodies. In the distal colon, ICC
      emerged at weeks 10-11 of the fetal period in the form of two parallel belts of
      densely packed cells extending at the submucous plexus (SMP) and the MP level.
      These cells correspond to ICC of the SMP (ICC-SMP) and ICC of the MP (ICC-MP).
      The simultaneous appearance of ICC at the SMP and MP level in the distal colon
      can be explained by the fact that there are differences in the migration of
      neural crest cells in particular portions of the digestive tube. In conclusion,
      in humans, there was a difference in the patterns of development of ICC in the
      distal colon compared to the rest of the gut.

PMID- 22652526
TI  - Serum 25-hydroxyvitamin D concentration, established and emerging cardiovascular
      risk factors and risk of myocardial infarction before the age of 60 years.
AB  - OBJECTIVE: We examined the relationships of serum 25-hydroxyvitamin D (25(OH)D)
      concentration to established and emerging cardiovascular risk factors and risk of
      myocardial infarction (MI) in a population-based case-control study of MI before
      the age of 60 years. METHODS: A total of 387 survivors of a first MI and 387 sex-
      and age-matched controls were included. Fasting blood samples drawn three months
      after the MI in cases and at the same time in the matched controls were used for
      biochemical analyses. RESULTS: Serum concentrations of 25(OH)D, adjusted for
      seasonal variation, were lower in cases than controls (55.0 (40.0-71.0) nmol/L vs
      60.5 (47.0-75.0) nmol/L; median (interquartile range); standardized odds ratio
      (OR) for MI with 95% confidence interval in univariable analysis: 0.80 (0.69
      0.93); p = 0.003). The 25(OH)D association with MI disappeared after adjustment
      for established and emerging risk factors (OR: 1.01 (0.82-1.25)). Current smoking
      and plasma levels of proinsulin and PAI-1 activity were independently associated
      with 25(OH)D in controls, whereas waist circumference, plasma triglycerides,
      proinsulin, PAI-1 activity and cystatin C, and non-Nordic ethnicity were
      independently associated with 25(OH)D in patients. Serial measurements of 25(OH)D
      (samples drawn <4 h and 3 months after the onset of MI) in 57 patients showed no
      systematic differences between sampling times. CONCLUSION: Vitamin D
      insufficiency, which is associated with a multitude of metabolic, procoagulant
      and inflammatory perturbations, is not independently related to premature MI.
      This suggests that vitamin D insufficiency either constitutes an epiphenomenon or
      increases the risk of MI by promoting established risk factor mechanisms that
      predispose to atherothrombosis.

PMID- 22652527
TI  - Associations of ankle-brachial index (ABI) with cerebral arterial disease and
      vascular events following ischemic stroke.
AB  - OBJECTIVES: Low ankle-brachial index (ABI), indicative of peripheral arterial
      disease (PAD), is a risk factor for stroke. ABI has been shown to be associated
      with cerebral arterial disease and prognosis following stroke. We studied the
      associations of the degree of ABI lowering with extracranial carotid disease
      (ECD), intracranial large artery disease (ICLAD), and subsequent vascular events
      in a prospective cohort of acute ischemic stroke patients. METHODS: ABI,
      extracranial and intracranial cerebral arteries were assessed in a blinded
      manner. ABI was categorized into 0.9-1.3 (normal), 0.8-0.89 (mildly lowered) and
      <0.8 (severely lowered). Follow-up data at 1 year were obtained from standardized
      telephone interviews and verified with medical records. RESULTS: Among the 1311
      patients, 73% had normal ABI, 13% had ABI 0.8-0.89 and 13% had ABI <0.8. Compared
      to patients with normal ABI, those with ABI<0.8 had higher prevalence of severe
      ECD (15% vs. 5%, p = 0.006) and ICLAD (72% vs. 48%, p = 0.003), even after
      adjustment for age, gender, hypertension, diabetes, hyperlipidemia, smoking,
      ischemic heart disease and atrial fibrillation (severe ECD p < 0.001, ICLAD p <
      0.001). At 1 year, patients with ABI <0.8 had a higher incidence of composite
      vascular events (19% vs. 11%, p = 0.02), stroke (15% vs. 10%, p = 0.06) and
      myocardial infarction (4% vs. 2%, p = 0.07) than patients with normal ABI.
      CONCLUSION: Among ischemic stroke patients, large cerebral arterial disease and
      incidence of subsequent vascular events at 1 year were associated with severe ABI
      lowering <0.8, but not with mild ABI lowering (0.8-0.89).

PMID- 22652528
TI  - Tissue transglutaminase (TG-2) modified amniotic membrane: a novel scaffold for
      biomedical applications.
AB  - The amniotic membrane (AM) is considered as a natural cell culture substrate and
      has occasionally been exploited in regenerative medicine especially for ocular
      surface reconstruction and dermal wound healing applications. However, its use is
      limited by its relatively weak mechanical strength, difficulty during manual
      handling and susceptibility to proteolytic degradation in vivo. Therefore, in
      this study we aimed to enhance the mechanical and biological characteristics of
      the AM by enzymatically cross-linking it using tissue transglutaminase (TG)-a
      calcium-dependent enzyme capable of forming stable epsilon(gamma-glutamyl)lysine
      cross-linkages. Using a biological catalyst such as TG does not only prevent
      denaturation during sample preparation but also minimizes the potential of
      residual chemical cross-linking agents compared to alternative methodologies.
      Human AM, sourced from elective caesarean sectioning, were treated with TG,
      bovine serum albumin and/or a no-treatment control. Samples were then compared in
      terms of their physical and (scanning electron microscopy (SEM), transparency,
      mechanical strength, susceptibility to proteolytic degradation) biological
      characteristics (in vitro cell culture, activation of dendritic cells (DC)) and
      their in vivo biocompatibility/angiogenic capacity (chick chorioallantoic
      membrane assay). TG-treated AM exhibited enhanced mechanical strength and greater
      resistance to proteolytic/collagenase degradation compared to the control(s). SEM
      imaging of the TG-treated membrane summarized a significantly closer association
      and greater interconnectivity of individual collagen fibres yet it had no effect
      on the overall transparency of the AM. In vitro cell culture demonstrated no
      detrimental effect of TG-treatment on the AM in terms of cell attachment,
      spreading, proliferation and differentiation. Moreover, an 'immune response' was
      not elicited based on extended in vitro culture with human-monocyte-derived DC.
      Interestingly, the TG-treated AM still allowed angiogenesis to occur and in some
      instances, demonstrated an enhancement compared to the control (n = 5). We hereby
      demonstrate that treating the AM with the cross-linking enzyme, TG, results in a
      novel biomaterial with enhanced mechanical and biological characteristics. Above
      all, this modified membrane demonstrates greater strength, maintains in vitro
      cell growth, retains optical transparency and allows angiogenesis to occur
      without inducing an immune response. Altogether, this study demonstrates the
      feasibility of TG as an alternate cross-linking treatment for the production of
      novel biomaterials and suggests that TG-treated AM may now be more commonly
      exploited as a therapeutic dressing for ocular or wound applications.

PMID- 22652529
TI  - Section 504 and student health problems: the pivotal position of the school
      nurse.
AB  - News reports illustrate controversies between parents and schools in response to
      student health problems. Today's school nurse is in a pivotal position for the
      avoidance and resolution of disputes not only by increasing awareness of student
      health conditions but also by having a working knowledge of legal developments
      under Section 504 and its sister statute-the Americans with Disabilities Act
      (ADA). The ADA amendments of 2008 have extended the standards for eligibility and
      expanded questions about school districts' obligations under Section 504 and the
      ADA. This article provides a comprehensive synthesis of recent case law and
      related legal developments under this pair of federal statutes, culminating in
      practical implications and professional recommendations for school nurses.

PMID- 22652530
TI  - Involvement of the endogenous cannabinoid 2 ligand 2-arachidonyl glycerol in
      allergic inflammation.
AB  - BACKGROUND: Cannabinoid (CB) 2 is expressed on immune and inflammatory cells.
      Identification of 2-arachidonyl glycerol (2-AG) and anandamide as endogenous CB2
      ligands has allowed investigations of the roles of CB2 and its endogenous ligand
      system in inflammatory cells. However, the roles of this receptor-ligand system
      in inflammatory and allergic immune responses in vivo have not been fully
      elucidated. METHODS: Two mouse allergy models, namely ear dermatitis induced by
      2,4-dinitrofluorobenzene and allergic bronchitis induced by ovalbumin, were
      analyzed for 2-AG amounts in allergic tissues, with reference to allergic and
      inflammatory symptoms. To investigate the gene expression via CB2 in inflammatory
      cells, human promyelocytic HL-60 cells were stimulated by the CB2 ligand 2-AG
      ether and analyzed using a DNA microarray. RESULTS: In the ear dermatitis model,
      the 2-AG amount increased upon serial 2,4-dinitrofluorobenzene challenges and was
      correlated with ear weight gain. The increased ear thickness in this allergy
      model was clearly suppressed in CB2 knockout mice, suggesting that the generated
      endogenous CB2 ligands induce ear thickness through aberrant inflammatory
      responses and remodeling mediated via CB2. In the allergic bronchitis model, the
      2-AG level in bronchoalveolar lavage was increased and sustained during the
      elevation of inflammatory cell infiltration. The DNA microarray analysis of human
      HL-60 cells revealed that 2-AG ether induced expressions of not only inflammatory
      chemokines/cytokines but also of cell growth factors. CONCLUSION: Our data
      strongly suggest that endogenous CB2 ligands upregulated upon disease progression
      in allergic models are involved in aberrant alterations of both inflammatory
      responses and tissue cell growth.

PMID- 22652531
TI  - In vitro anthelmintic activity of five tropical legumes on the exsheathment and
      motility of Haemonchus contortus infective larvae.
AB  - This study investigated the in vitro anthelmintic (AH) activity of five tropical
      legume plants [Arachis pintoi CIAT 22160 (A.p. 22160), Gliricidia sepium,
      Cratylia argentea (C.a. Yacapani), C. argentea CIAT 22386 (C.a. 22386), C.
      argentea Veranera (C.a. Veranera)] against Haemonchus contortus infective larvae
      and the role of tannins/polyphenolic compounds in the AH effect. Lyophilized leaf
      extracts of each plant were evaluated using the Larval Exsheathment Inhibition
      Assay (LEIA) and the larval migration inhibition assay (LMIA). The role of
      tannins/polyphenolic compounds in the AH effect was evaluated in both assays
      using polyethylene glycol (PEG) to remove tannins from the solutions. At the
      highest concentration (1200MUg of extract/ml), A. pintoi 22160, C.a. Yacapani,
      C.a. Veranera and C.a. 22386 completely inhibited the exsheathment process of H.
      contortus (P<0.01). At the same concentration (1200MUg of extract/ml), the
      inhibition of larval migration for C.a. 22386, C.a. Veranera and G. sepium was
      66.0%, 35.9% and 39.2% (relative to the PBS control), respectively. In both
      bioassays (LEIA and LMIA), the AH effect shown by each plant was blocked after
      the addition of polyethylene glycol (PEG), corroborating the role of
      tannins/polyphenolic compounds.

PMID- 22652532
TI  - Germline mutations in the DNA damage response genes BRCA1, BRCA2, BARD1 and TP53
      in patients with therapy related myeloid neoplasms.
AB  - BACKGROUND: Therapy related myeloid neoplasms (t-MNs) are complex diseases
      originating from an interplay between exogenous toxicities and a susceptible
      organism. It has been hypothesised that in a subset of cases t-MNs develop in the
      context of hereditary cancer predisposition syndromes. METHODS: The study
      systematically evaluated pedigrees of patients with t-MNs for cancer incidences
      and the possibility of a hereditary cancer predisposition syndrome. In addition,
      mutational analyses were performed using constitutional DNA from index patients,
      and deleterious heterozygous germline mutations were assessed for loss of
      heterozygosity in sorted leukaemic cells by single nucleotide polymorphism array.
      RESULTS: A nuclear pedigree was obtained in 51/53 patients with t-MNs resulting
      in a total of 828 individuals analysed. With a standardised incidence ratio of
      1.03 (95% CI 0.74 to 1.39), the tumour incidence of first- degree relatives was
      not increased. However, six pedigrees were suggestive for a hereditary breast and
      ovarian cancer syndrome, three of a Li-Fraumeni like syndrome, and three index
      patients showed multiple primary neoplasms. Mutational analysis revealed two
      BRCA1 (c.3112G->T, c.5251C->T), one BRCA2 (c.4027A->G), two BARD1 (C557S) and
      four TP53 germline mutations (g.18508_18761delinsGCC, c.847C->T,
      c.845_848dupGGCG, c.1146delA) in nine of 53 (17%) index patients with t-MNs. Loss
      of heterozygosity in leukaemic cells was demonstrated for the BRCA1c.3112G->T and
      TP53c.845_848dupGGCG mutations, respectively. CONCLUSION: It is concluded that a
      proportion of patients with t-MNs carry cancer susceptibility mutations which are
      likely to contribute to therapy related leukaemogenesis.

PMID- 22652533
TI  - A Finnish founder mutation in RAD51D: analysis in breast, ovarian, prostate, and
      colorectal cancer.
AB  - BACKGROUND: RAD51D and RAD54L are involved in homologous recombination, and rare
      mutations in RAD51D were recently found in breast-ovarian cancer families. This
      study investigated RAD51D and RAD54L for mutations in breast and ovarian cancer
      patients in the Finnish population. METHODS: The study sequenced the RAD51D and
      RAD54L genes in 95 breast and/or ovarian cancer families and genotyped the
      identified mutation in an additional 2200 breast and 553 ovarian cancer patients
      and 2102 population controls. To investigate the role of the mutation in other
      common cancers, 1094 prostate and 980 colorectal cancer patients were genotyped.
      RESULTS: In the screening of RAD51D, one deleterious founder mutation c.576+1G>A
      was identified in two breast-ovarian cancer families. No mutations were found in
      RAD54L. Altogether, the c.576+1G>A mutation was detected in 5/707 patients with a
      personal or family history of ovarian cancer (OR 9.16, 95% CI 1.07 to 78.56;
      p=0.024), with the highest frequency among breast-ovarian cancer families (3/105
      vs 1/1287 controls, OR 37.82, 95% CI 3.90 to 366.91; p=0.0016), but no elevated
      frequency among breast cancer patients/families (2/2105, p=1). The mutation was
      not found among prostate or colorectal cancer patients. CONCLUSIONS: The results
      of this study on familial and unselected breast, ovarian, colorectal, and
      prostate cancer patients suggest that RAD51D is primarily a moderate penetrance
      susceptibility gene for ovarian cancer, with clinical significance for the
      carriers.

PMID- 22652534
TI  - Mutation in RAB33B, which encodes a regulator of retrograde Golgi transport,
      defines a second Dyggve--Melchior--Clausen locus.
AB  - BACKGROUND: Dyggve--Melchior--Clausen syndrome (DMC) is a chondrodysplasia that
      bears significant phenotypic resemblance to mucopolysaccharidosis type IV
      (Morquio disease). Autosomal recessive mutations in DYM are known to cause this
      disease through its role in Golgi organisation and intracellular traffic, but
      genetic heterogeneity is suspected. METHODS: A family with DMC and normal
      intellectual development underwent clinical evaluation followed by autozygosity
      mapping and exome sequencing. Immunoblot and immunofluorescence analyses were
      performed to characterise the effect of the mutation. RESULTS: This multiplex
      consanguineous family links to a novel locus on 4q31.1. Exome sequencing revealed
      a missense mutation in RAB33B, which encodes a Rab protein with an established
      role in retrograde Golgi traffic. The mutation qualitatively replaces the
      invariant lysine residue in the guanine nucleotide-binding domain of this small
      GTPase protein and leads to marked protein deficiency, making it the likely
      causative mutation of DMC in this family. CONCLUSION: This study identifies a new
      DMC gene and highlights the role of intracellular traffic in the pathogenesis of
      this disease.

PMID- 22652538
TI  - The neural correlates of maternal sensitivity: an fMRI study.
AB  - Research on maternal neural response to infant distress highlights circuits that
      may underlie differences in quality of maternal behavior. However, it is far from
      clear which circuits are relevant to maternal sensitivity, as opposed to other
      maternal behavioral dimensions, particularly after the early postpartum. This
      study examined maternal sensitivity, intrusiveness, and mother-infant dyadic
      harmony as correlates of mothers' neural responses to the cries of their own
      infants. Twenty-two primiparous mothers were observed during an interaction with
      their infants at 18 months postpartum. In a separate functional neuroimaging
      session, mothers were exposed to their own infant's cry sound, as well as
      unfamiliar infant's cry and control sounds. Mothers who displayed more sensitive
      behaviors with their infant exhibited greater activation to their own infant's
      cry compared to that of an unfamiliar infant in the right frontal pole and
      inferior frontal gyrus. Mothers who displayed more intrusive behaviors with their
      infant showed greater activation in the left anterior insula and temporal pole,
      while mothers who had more harmonious interactions with their infant displayed
      greater activation in left hippocampal regions. The roles of these areas in the
      regulation of maternal emotion and stress, self and other awareness, and empathy
      are examined.

PMID- 22652540
TI  - Magnetoresistance of rolled-up Fe3Si nanomembranes.
AB  - Magnetotransport of individual rolled-up Fe(3)Si nanomembranes is investigated in
      a broad temperature range from 4.2 K up to 300 K in pulsed magnetic fields up to
      55 T. The observed magnetoresistance (MR) has the following pronounced features:
      (i) MR is negative in the investigated intervals of temperature and magnetic
      field; (ii) its magnitude increases linearly with the magnetic field in a low
      field region and reveals a gradual trend to saturation when the magnetic field
      increases; (iii) the MR effect becomes more pronounced with increasing
      temperature. These dependences of MR on the magnetic field and temperature are in
      line with predictions of the spin-disorder model of the spin-flip s-d interaction
      assisted with creation or annihilation of magnons, which is expected above a
      certain critical temperature. Comparison of the MR features in rolled-up and
      planar samples reveals a substantial increase of the critical temperature in the
      rolled-up tube, which is attributed to a new geometry and internal strain arising
      in the rolled-up nanomembranes, influencing the electronic and magnetic
      properties of the material.

PMID- 22652541
TI  - Structural characteristics and harmonic vibrational analysis of the stable
      conformer of 2,3-epoxypropanol by quantum chemical methods.
AB  - The FT-IR and FT-Raman spectra of H bond inner conformer of 2,3-epoxypropanol
      have been recorded in the regions 3700-400 and 3700-100 cm(-1), respectively. The
      spectra were interpreted in terms of fundamentals modes, combination and overtone
      bands. The normal coordinate analysis was carried out to confirm the precision of
      the assignments. The structure of the conformers H bond inner and H bond outer1
      were optimised and the structural characteristics were determined by density
      functional theory (DFT) using B3LYP and MP2 methods with 6-31G** and 6-311++G**
      basis sets. The vibrational frequencies were calculated in all these methods and
      were compared with the experimental frequencies which yield good agreement
      between observed and calculated frequencies. The electronic properties HOMO and
      LUMO energies were measured by time-dependent TD-DFT approach.

PMID- 22652542
TI  - Structural, proton-transfer, thermodynamic and nonlinear optical studies of (E)-2
      ((2-hydroxyphenyl)iminiomethyl)phenolate.
AB  - Recently, the study of imine-bridged organics is interested in proton-transfer
      and photo-responsive material fields. Herein, we make a investigation on the
      structural, thermodynamic and nonlinear optical properties of (E)-2-((2
      hydroxyphenyl)iminiomethyl)phenolate (HPIMP). The structural varieties of the
      studied compound are characterized by the X-ray single crystal diffraction and
      vibrational spectral techniques, as well as the vibrational spectral bands are
      precisely ascribed to the studied structure with the aid of DFT theoretical
      calculations. The experimental results of the FT-IR and X-ray measurements supply
      good proofs to reveal the proton-transfer procedures of HPIMP, and exhibit that
      the studied compound is a good proton-transfer model. In addition, the
      thermodynamic properties are obtained from the theoretical vibrations of the
      optimized HPIMP. The linear polarizability (alpha(0)) and first-order
      hyperpolarizabilities (beta(0)) respectively present the values of 26.28 A(3) and
      7.41*10(-30) cm(5)/esu predicated theoretically by the DFT-B3lYP method at 6
      31G(d) level, which indicates that the studied compound is a promising nonlinear
      optical material candidate.

PMID- 22652535
TI  - Amino acid balance with extended daily diafiltration in acute kidney injury.
AB  - BACKGROUND: The impact of hybrid dialysis therapies on amino acid (AA) balance in
      critically ill patients with acute kidney injury is unknown. METHODS: We examined
      prospectively the AA balance with extended daily diafiltration (EDDF). RESULTS:
      We studied 7 patients. AA clearances with EDDF ranged from 21.6 ml/min
      (tryptophan) to 66.9 ml/min (taurine). AA loss was 4.2 (IQR 1.4-12.3) g/day and
      4.5% of daily protein intake for patients on enteral nutrition (EN). Percentage
      AA loss per hour on EDDF was highest for glutamine (32.1%) and lowest for
      glutamic acid (0.8%). Blood AA levels correlated with corresponding EDDF losses.
      Median total nitrogen appearance was 25.0 (IQR 20.6-29.3) g/day for patients on
      EN. This resulted in a negative nitrogen balance of -10.7 (IQR -16.6 to -1.4)
      g/day, of which 6.5% was attributable to AA loss. CONCLUSIONS: AA loss with EDDF
      was limited, but with much individual variability, and contributed to a strongly
      negative daily nitrogen balance.

PMID- 22652539
TI  - Dual roles of Atg8-PE deconjugation by Atg4 in autophagy.
AB  - Modification of target molecules by ubiquitin or ubiquitin-like (Ubl) proteins is
      generally reversible. Little is known, however, about the physiological function
      of the reverse reaction, deconjugation. Atg8 is a unique Ubl protein whose
      conjugation target is the lipid phosphatidylethanolamine (PE). Atg8 functions in
      the formation of double-membrane autophagosomes, a central step in the well
      conserved intracellular degradation pathway of macroautophagy (hereafter
      autophagy). Here we show that the deconjugation of Atg8-PE by the cysteine
      protease Atg4 plays dual roles in the formation of autophagosomes. During the
      early stage of autophagosome formation, deconjugation releases Atg8 from non
      autophagosomal membranes to maintain a proper supply of Atg8. At a later stage,
      the release of Atg8 from intermediate autophagosomal membranes facilitates the
      maturation of these structures into fusion-capable autophagosomes. These results
      provide new insights into the functions of Atg8-PE and its deconjugation.

PMID- 22652543
TI  - Subtractive-FTIR spectroscopy to characterize organic matter in lignite samples
      from different depths.
AB  - Organic matter present in lignite samples collected from different depths (i.e.
      top, mid and bottom) of lignite source, Ilgin, Konya province, was examined by
      using subtractive-FTIR-ATR spectroscopy. FTIR spectra were recorded on (i)
      original samples, (ii) the samples dried at 105  degrees C and (iii) the samples
      acid-treated and dried. After a combustion process performed for each sample at
      650  degrees C for 15 min, the spectra of samples were recorded and subtracted
      from the spectra of untreated samples. Hence, a software-based subtraction made
      it possible to acquire a representative spectra related with organic matter. As
      the contribution of the bands related with inorganic constituents in lignite
      samples were eliminated after spectrum-subtraction procedure, difference-spectra
      led analyzing the spectra related with organic matter in lignite samples,
      reasonably. Furthermore, the bands related with acidic functional groups,
      aromatic and aliphatic structures were analyzed on the basis of difference
      spectra, easily. From the difference-spectra it was shown that an acid-treatment
      process under mild conditions caused shift in some specific bands related with
      carbonyl groups of carboxyls so that the band at around 1710 cm(-1) arisen, while
      the intensity of the band at around 1420 cm(-1) was diminished. Through the acid
      treatment process, acidic groups in lignite samples from different depths were
      thought to be turned into similar forms by protonation and/or stripping of metal
      ions originally bonded. Difference-spectra acquired for acid-treated samples made
      it possible to evaluate the form of carboxylic acid groups present in the studied
      samples under specific environmental conditions. Hence, a facile and
      environmentally-friendly methodology was used to analyze organic matter in
      lignite by using FTIR spectra, and valuable information was acquired about the
      aliphatic, aromatic and acidic character of the studied lignite samples collected
      from different depths. The proposed methodology seems to be promising in
      acquiring approximate representative spectra for lignite organic matter by using
      little or no chemicals.

PMID- 22652544
TI  - Serum angiopoietin-like protein 3 concentrations in rheumatic diseases.
AB  - Angiopoietin-like protein 3 (Angptl3) is one of the angiogenic cytokines that
      stimulates endothelial cell adhesion, migration, and neovascularization. No link
      has been established between Angptl3 and rheumatic diseases such as systemic
      sclerosis or dermatomyositis (DM). In this study, we determined the serum Angptl3
      levels in patients with various rheumatic diseases, and tried to evaluate the
      possibility that serum levels of Angptl3 can be a useful disease marker. Serum
      samples were collected from 21 SSc patients, 10 systemic lupus erythematosus
      (SLE) patients, 21 DM patients, 5 polymyositis (PM) patients and 11 patients with
      clinically amyopathic DM (CADM) as well as 12 healthy volunteers. Levels of serum
      Angptl3 were measured with a specific ELISA kit. There was a significant increase
      of serum Angptl3 levels in patients with SSc or DM (p<0.05). Levels of serum
      Angptl3 were also slightly higher in patients with ADM, PM or SLE compared with
      healthy controls, but not statistically significant. Myoglobin levels were
      significantly higher in DM patients with increased serum Angptl3 levels than
      those with normal levels (p<0.05). In addition, among patients with SSc, the
      prevalence of cutaneous ulcers was significantly greater in patients with
      elevated Angptl3 levels than those with normal levels (p<0.05). Serum Angptl3
      levels may be associated with the pathogenesis of muscle involvement in DM
      patients and microangiopathy in SSc patients. Clarifying the role of Angptl3 in
      each rheumatic disease may lead to further understanding of the pathogenesis and
      new therapeutic approaches.

PMID- 22652547
TI  - Field-effect transistor-based solution-processed colloidal quantum dot
      photodetector with broad bandwidth into near-infrared region.
AB  - We demonstrate a solution-processed colloidal quantum dot (CQDs) photodetector
      with the configuration of a field-effect transistor (FET), in which the drain and
      source electrodes are fabricated by a shadow mask. By blending PbS CQDs into the
      hybrid blend, poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C(61)-butyric acid
      methylester (PCBM), the photosensitive spectrum of the nanocomposite blend is
      extended into the near-infrared region. A FET-based photodetector ITO/PMMA (180
      nm)/P3HT:PCBM:PbS (110 nm)/Al, in which PMMA (polymethylmethacrylate) acts as the
      dielectric layer and P3HT:PCBM:PbS (in weight ratio of 1:1:1) as the active
      layer, shows a broad spectral bandwidth, a responsivity of 0.391 mA W(-1) and a
      specific detectivity of 1.31 * 10(11) Jones  are obtained at V(GS) = 1 V under
      600 nm illumination with an intensity of 30 MUW cm(-2). Therefore, it provides an
      easy way to fabricate such a FET-based photodetector with a channel length of
      some hundreds of micrometers by a shadow mask.

PMID- 22652546
TI  - Predicting the oral absorption of a poorly soluble, poorly permeable weak base
      using biorelevant dissolution and transfer model tests coupled with a
      physiologically based pharmacokinetic model.
AB  - For predicting food effects and simulating plasma profiles of poorly soluble
      drugs, physiologically based pharmacokinetic models have become a widely accepted
      tool in academia and the pharmaceutical industry. Up till now, however,
      simulations appearing in the open literature have mainly focused on BCS class II
      compounds, and many of these simulations tend to have more of a "retrospective"
      than a prognostic, predictive character. In this work, investigations on the
      absorption of a weakly basic BCS class IV drug, "Compound A", were performed. The
      objective was to predict the plasma profiles of an immediate release (IR)
      formulation of Compound A in the fasted and fed state. For this purpose, in vitro
      biorelevant dissolution tests and transfer model experiments were conducted.
      Dissolution and precipitation kinetics were then combined with in vivo post
      absorptive disposition parameters using STELLA(r) software. As Compound A not
      only exhibits poor solubility but also poor permeability, a previously developed
      STELLA(r) model was revised to accommodate the less than optimal permeability
      characteristics as well as precipitation of the drug in the fasted state small
      intestine. Permeability restrictions were introduced into the model using an
      absorption rate constant calculated from the Caco-2 permeability value of
      Compound A, the effective intestinal surface area and appropriate intestinal
      fluid volumes. The results show that biorelevant dissolution tests are a helpful
      tool to predict food effects of Compound A qualitatively. However, the plasma
      profiles of Compound A could only be predicted quantitatively when the results of
      biorelevant dissolution test were coupled with the newly developed PBPK model.

PMID- 22652548
TI  - Design and characterization of a novel amphiphilic chitosan nanocapsule-based
      thermo-gelling biogel with sustained in vivo release of the hydrophilic anti
      epilepsy drug ethosuximide.
AB  - Thermo-gelling injectable nanogels, with no burst release of loaded drug, were
      prepared by a simple route by combining self assembled nanocapsules of
      amphiphilically modified chitosan with glycerophosphate di-sodium salt and
      glycerol. The potential as a depot drug delivery system was demonstrated in vivo
      through the therapeutic effect of ethosuximide (ESM) loaded nanogels, suppressing
      spike wave discharges (SWDs) in Long Evan rat model. Simultaneously clearance of
      gels from the site of administration was monitored non-invasively using MRI. The
      gel structure was characterized using TEM and SEM, confirming the gels to be an
      assembly of nanocapsules and using two-photon microscopy to visualize the network
      structure. In vitro drug release studies using ESM revealed that the nanogels
      exhibited extended, mostly Fickian release. Finally, all investigated
      formulations displayed excellent cytotoxicity data determined by MTT assay using
      human retinal pigmented epithelium cells. All presented properties are highly
      desirable for injectable depot gels for drug delivery.

PMID- 22652549
TI  - Carbosilane dendrimer nanotechnology outlines of the broad HIV blocker profile.
AB  - Researchers have been working hard for more than 20 years to develop safe and
      effective microbicides to empower women to better control their own sexual life
      and to protect themselves against HIV and other sexually transmitted infections
      (STIs). Microbicide classes include moderately specific macromolecular anionic
      polymers that block HIV and other STIs, and HIV specific drugs that inhibit viral
      entry and reverse transcription. Based on innovative nanotechnology design, we
      showed a novel water-soluble anionic carbosilane dendrimer (2G-S16) as a
      propitious molecule against HIV-infection. A state-of-the-art research was
      accomplished that focused on biomedical cutting-edge techniques such as in vitro
      and in vivo cytotoxicity assays performed on female rabbit genital tracts,
      simulate in vitro model of vaginal epithelium in order to evaluate HIV
      transmission blockade through the monolayer, complete gene expression profiling
      experiment to study deregulated genes after 2G-S16 exposition, molecular dynamics
      simulation of 2G-S16 molecule against principal proteins of HIV particles and pro
      and anti-inflammatory cytokine profile study. Therefore, a high-throughput study
      and detailed analysis of the results were achieved in this article. We provided
      promising outcomes to encourage 2G-S16 as a hopeful microbicide.

PMID- 22652550
TI  - An unusual case of spinal dysraphism with four splits including three posterior
      spurs.
AB  - BACKGROUND: Composite-type split spinal cord malformation (SCM) is very rare and
      results from 2 separate foci of ectoendodermal adhesions and endomesenchymal
      tracts leading to the development of SCM with an intervening normal cord in the
      same patient. Posterior spurs are even rarer. We report a unique case of
      composite SCM, where the patient had 3 posterior bony spurs and 1 fibrous spur at
      different levels. To our knowledge, this is the first reported case of a patient
      having composite-type SCM with posterior spurs at 3 different levels. CLINICAL
      PRESENTATION: A 3-year-old girl presented to us with progressively worsening
      scoliosis. Neurological examination was unremarkable except for mild weakness in
      the left lower limb. Three-dimensional CT imaging demonstrated posterior bony
      spurs located at T(6), T(12) and L(3) levels. The patient underwent T(11)-L(5)
      laminoplasty and T(5)/T(6) laminectomy and excision of SCM type 1 with division
      of the thickened filum terminale. All the bony spurs arose from the inner surface
      of the lamina, where the base of the spur was located. CONCLUSIONS: The unique
      point of this case report is the rarity of such a presentation. Careful planning
      and knowledge of the occurrence of such conditions can make surgery in these
      children safe, and all the levels can be treated in a single setting.

PMID- 22652551
TI  - The effect of temperature and mobile phase composition on separation mechanism of
      flavonoid compounds on hydrosilated silica-based columns.
AB  - We investigated the effects of mobile phase composition on the retention of
      flavones on four different hydrosilated C silica-based columns in buffered
      aqueous acetonitrile. Cogent UDC cholesterolTM and Cogent bidentate C18TM columns
      show significant dual reversed-phase/normal-phase retention behavior, while
      Cogent Diamond hydrideTM and Cogent Silica hydrideTM columns show negligible
      retention in the reversed-phase mode. The effect of the aqueous acetate buffer
      concentration on retention factors of flavones over the full mobile phase
      composition range, including both aqueous normal-phase (ANP) and reversed-phase
      mechanisms, can be described by a four-parameter equation for dual-retention
      mechanism. At increasing temperature, the retention factors and peak widths
      decrease both in the aqueous normal phase and in the reversed phase mobile phase
      range. In agreement with van't Hoff model, linear lnk versus 1/T plots were
      observed, showing a single retention mechanism in the highly organic normal-phase
      and in highly aqueous reversed-phase mobile phase ranges. From among the
      stationary phases tested, Cogent UDC cholesterolTM column has high temperature
      stability (up to 100  degrees C) and provides most selective and efficient
      separations of flavones both in the ANP and in the RP modes with almost reversed
      elution order.

PMID- 22652552
TI  - Reversed-phase ion-pair liquid chromatography electrospray ionization tandem mass
      spectrometry for separation, sequencing and mapping of sites of base modification
      of isomeric oligonucleotide adducts using monolithic column.
AB  - In this manuscript, an efficient high resolution reversed phase-ion pairing
      liquid chromatography electrospray ionization tandem mass spectrometry (RP-IP-LC
      MS/MS) method for separation of isomeric modified oligonucleotides using a
      polymeric (styrene-divinylbenzene) monolithic capillary column is presented. The
      effects of different ion pairing reagents (IPR), their concentration, mobile
      phase additives and conditions were evaluated towards achieving the highest
      possible resolution and chromatographic separation of isomeric oligonucleotides.
      Ion pairing reagents and mobile phase conditions were evaluated using as model N
      acetylaminofluorene [AAF] adducted ss-oligonucleotides (CCC CGA GCA ATC TCA AT).
      The optimized mobile phase conditions were then applied for the mapping of sites
      of base modification of AAF adducted 15-base pair oligonucleotide fragments
      containing codon 135 of the p53 gene and for profiling a complex synthetic
      oligonucleotide mixture. The optimized method utilizes a monolithic poly(styrene
      divinylbenzene) capillary column, triethylammonium bicarbonate as ion pairing
      reagent and methanol as organic modifier to perform IP-RPLC-ESI-MS/MS separation.
      The results show that the method is simultaneously applicable not only to
      oligonucleotide fragments adducted separately by different carcinogens but also
      to the analysis of multiple adducts in the same oligonucleotide fragment in a
      single experiment. The method presents itself as a tool for the identification,
      characterization and mapping of oligonucleotide adducts as biomarkers for DNA
      damage from carcinogens.

PMID- 22652553
TI  - In vitro degradation of electrodeposited calcium phosphate coatings by osteoclast
      like cells.
AB  - The aim of this study is to investigate the in vitro degradation of
      electrolytically deposited calcium phosphate coatings in the presence of
      osteoclast-like cells. Titanium alloy plates electrolytically coated with calcium
      phosphate with or without chitosan were incubated with RAW264.7 cells for 14
      days. The TRAP activity was measured and the cell attachment and proliferation
      capacity were analyzed. The calcium ion concentrations in the culture medium
      before and after incubation were calculated. Both coatings were observed with
      scanning electron microscopy and characterized through an x-ray diffractometer
      and Fourier transform infrared spectrum. The RAW264.7 cells differentiated into
      TRAP-positive osteoclast-like cells on both coatings after 7 days. Although
      presenting different cell attachment pattern, the RAW264.7 cells demonstrated the
      similar TRAP activity and proliferation capacity. It was found that the calcium
      ion concentrations in the medium decreased at the beginning, but increased after
      11 and 14 days. The chitosan containing coatings had higher Ca(2+) concentration
      in the medium compared to that without chitosan. Besides, the incubation of
      coatings with cells induced higher calcium ion concentrations than those without
      cells at day 11 and day 14. Despite the structural changes of dissolution pits
      and osteoclastic resorption lacunae present on both coatings, the x-ray
      diffractometer and Fourier transform infrared spectrum showed few alternations in
      their chemical compositions. Both electrodeposited calcium phosphate coatings can
      be resorbed by osteoclast-like RAW264.7 cells and dissolved in the culture medium
      in vitro. The degradation brings little change to the chemical compositions of
      both coatings.

PMID- 22652555
TI  - Metallodynameric membranes--toward the constitutional transport of gases.
AB  - The adequate selection of macromonomers, dialdehyde core connectors and of
      coordinating metal ions makes possible the generation of metallodynameric
      materials, allowing the fine modulation of the gas transport through rubbery
      membranes.

PMID- 22652554
TI  - Effect of genetic polymorphism of ALOX15 on aspirin-exacerbated respiratory
      disease.
AB  - BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome
      associated with chronic inflammation in the airways coincident with chronic
      rhinitis, sinusitis, recurrent polyposis and asthma. Eosinophils are the key
      inflammatory cells in the development of AERD. AERD has been attributed to
      abnormalities of the arachidonic acid metabolism, but the pathogenesis of AERD is
      not fully understood. Our aim was to investigate the genetic contribution of the
      arachidonate 15-lipoxygenase gene (ALOX15) to the development of AERD. METHODS:
      We enrolled 171 patients with AERD, 229 patients with aspirin-tolerant asthma,
      and 195 normal healthy controls in a Korean population. Three polymorphisms (
      427G/A, -272C/A, -217G/C) in the promoter region of ALOX15 were genotyped. The
      functional variability of the promoter polymorphisms were analyzed by luciferase
      reporter activity assay. RESULT: No significant difference in the genotype
      frequency of the ALOX15 genetic polymorphism was found. Peripheral total
      eosinophil count was significantly higher in the patients carrying the GG
      genotype of the -427G/A polymorphism (p = 0.016). Similarly, the patients
      carrying haplotype 1 (ht1) (GCG) of -427G/A, -272C/A and -217G/C showed a
      significantly higher total eosinophil count compared to the other haplotypes (p =
      0.008) in the AERD group. The promoter activity of the ht1 (GCG) construct was
      significantly higher compared to that of the ht3 (AGG) construct in A549 and U937
      cells (both p < 0.001). CONCLUSION: These results suggest that the promoter
      polymorphisms of the ALOX15 gene affect ALOX15 activity leading to increased
      eosinophil infiltration in AERD patients.

PMID- 22652556
TI  - On-line haemodiafiltration improves response  to calcifediol treatment.
AB  - INTRODUCTION: 25-hydroxy vitamin D (25-OH-vit D) levels in the blood are
      associated with multiple pathologies. "Normal" values have been defined based on
      cardiovascular risk, and under this framework, patients with chronic kidney
      disease often have a deficit. 25-OH-vit D replacement in patients on
      haemodialysis (HD), in which dosage has not yet been clearly established, is
      becoming a constant in our daily practice. OBJECTIVE: To assess whether dialysis
      technique influences the baseline concentration of 25-OH-vitamin D and the
      response to supplements. METHOD: Prospective observational study of two cohorts
      of patients, those patients treated with calcifediol and those untreated
      (controls). Blood levels of Ca, P, PTH, and 25-OH-vit D were measured in 59
      prevalent patients on HD (35 male; mean age: 65.2 (15.7) years) in November 2010.
      Thirty-six patients with 25-OH-vit D<10 ng/ml were treated with weekly
      calcifediol (Hidroferol(r), 1 ampoule: 266 MUg) since January 2011, which was
      administered after HD by a nurse. They received 6 doses, and blood levels were
      measured again in March 2011. We compared the response based on the technique of
      HD (online haemodiafiltration [OL-HDF] vs HD). RESULTS: Mean baseline values
      (n=59): 25-OH-vit D: 9.8 (7.0)ng/ml, Ca: 9.3 (0.5)mg/dl, P: 4.5 (1.4)mg/dl, and
      iPTH: 299 (224)pg/ml. There were no differences by age, sex, or dialysis
      technique (HD vs OL-HDF). Treated patients (n=36): 25-OH-vit D levels rose from
      6.2 (3.4)ng/ml to 51 (22.9)ng/ml (P<.0001), without significant changes in Ca.
      Serum phosphate increased an average of 0.6 (1.4)mg/dl, from 4.4 mg/dl to 5mg/dl,
      (P=.015). PTH decreased an average of 85 (208)pg/ml (P=.023). In these patients,
      the indication for phosphate binders increased by an average dose equivalent of
      0.47 (0.82)mg/dl (P<.001). The 13 patients under treatment with OL-HDF reached 25
      OH-vit D levels significantly higher than the 23 treated on HD: 63 (21)ng/ml vs
      43 (21)ng/ml (P=.011). Dual treatment with native and active Vit D was associated
      with significantly increased levels of P (P=.043). Untreated patients (n=23): 25
      OH-vit D levels decreased from 15.3 (7.5)ng/ml in November to 11.1 (6.8)ng/ml in
      March (P<.01), without significant changes in P or PTH and without differences
      according to age. 25-OH-vit D levels declined in patients on HD (15) but not in
      patients on OL-HDF. CONCLUSION: The patients on haemodialysis have low or very
      low baseline values for 25-OH-vit D. The response to treatment with calcifediol
      is good, with the most marked improvement occurring in patients on OL-HDF.
      Furthermore, 25-OH-vit D levels decreased in untreated patients, which was
      probably correlated with the lower sun exposure in winter. Some patients
      experienced an increase in phosphataemia despite increasing the dosage of
      phosphate binders, mainly in those receiving treatment with active vitamin D.

PMID- 22652557
TI  - Is ultrasound follow-up necessary in humero-axillary prosthetic arteriovenous
      fistulas for haemodialysis?
AB  - AIM: To evaluate through a specific trial on vascular access fistulas (T-VAF),
      the impact of intensive follow-up controls on the permeability of humero-axillary
      fistulas (Hax-AVF). PATIENTS AND METHOD: Retrospective study. Between January
      2005 and December 2009, 108 Hax-AVF were implanted. From June 2007 a T-AVF was
      established. A preoperative duplex was performed and a follow-up control carried
      out a month after the intervention and subsequently every 3 months. RESULTS: An
      analysis was made of the permeability of 57 Hax-AVF carried out between June 2007
      and December 2009 (T-AVF Group), in comparison to 51 interventions performed
      during the previous 30 months (Control Group). No differences in the permeability
      achieved were found at 12 and 24 months, with a secondary permeability at 12
      months of 49% in the T-AVF Group and 52% in the Control Group. The percentage of
      patients needing to be re-operated was inferior in the T-AVF Group (35%) than in
      the Control Group (67%) p=0.02. The re-operation per patient average was lower in
      the T-AVF Group than in the Control Group (0.49 vs. 1.18 p=0.01). The patients of
      the TAVF Group underwent a lesser number of re-operations for obstruction as
      opposed to the Control Group (0.42 vs 1.04 p=0.01). CONCLUSIONS: In our
      experience, the intensive follow-up controls did not improve the permeability of
      the Hax-AVF, although re-operations due to obstruction did diminish. The follow
      up of these access fistulas should be clinical based on hemodialysis data,
      leaving ultrasonographic evaluation for those cases where a malfunction is
      suspected.

PMID- 22652559
TI  - Multifunctional role of an ionic liquid in melt-blended poly(methyl
      methacrylate)/ multi-walled carbon nanotube nanocomposites.
AB  - Poly(methyl methacrylate) (PMMA)/multi-walled carbon nanotube (MWNT)
      nanocomposites with a homogeneous dispersion of MWNTs have been fabricated by a
      simple melt-mixing method in the presence of a room-temperature ionic liquid, 1
      butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF6]. It has been found that
      the ionic liquid provided multiple functions in the preparation of the
      nanocomposites: (1) the ionic liquid acts as an effective compatibilizer to
      significantly improve the dispersion of MWNTs in the PMMA matrix; (2) the ionic
      liquid is an efficient plasticizer for the prepared nanocomposites, inducing a
      drastically reduced glass transition temperature in the PMMA matrix; (3) the
      ionic liquid acts as a processing aid for the melt processing of PMMA/MWNT
      nanocomposites; (4) the ionic liquid increases the electrical conductivity as a
      dopant. This strategy is free of solvents and compatible with industrial
      applications, which opens new avenues for the larger-scale fabrication of
      polymer/carbon nanotube nanocomposites.

PMID- 22652558
TI  - Long-term treatment with the pure anti-estrogen fulvestrant durably remodels
      estrogen signaling in BG-1 ovarian cancer cells.
AB  - Most ovarian cancers are estrogen-positive and hormonal treatments using anti
      estrogens or aromatase inhibitors are under investigation for treating the tumors
      that are resistant to conventional therapies. In this study, the long-term
      effects of two anti-estrogens, namely 4-hydroxytamoxifen and fulvestrant (or
      ICI182,780), were investigated in ERalpha-positive BG1 epithelial ovarian cancer
      cells. To this aim, cells were grown in the presence of anti-estrogen
      concentrations that were sufficient to saturate the estrogen receptors, but were
      neither cytotoxic nor cytostatic as indicated by the absence of inhibition of
      cell proliferation. In these conditions and despite the lack of cytostatic effect
      of the drugs, long-term treatment (3 months) with the pure anti-estrogen
      fulvestrant induced a specific, reproducible and irreversible inhibition of
      ERalpha expression. This inhibition was accompanied by loss of estrogen-induced
      cell proliferation and gene expression as indicated by the analysis of several
      estrogen-responsive genes. ERalpha down-regulation was not linked to deregulated
      expression of transcription factors which drive ERalpha transcription and did not
      involve DNA methylation or histone deacetylation. Altogether, these results
      demonstrate that non-cytotoxic concentrations of pure anti-estrogens affect
      estrogen signaling and might be relevant for the treatment for ovarian cancers.

PMID- 22652560
TI  - Hemodialysis with a dialyzer loaded with argatroban may be performed in vivo
      without a systemic anticoagulant.
AB  - BACKGROUND/AIMS: Anticoagulation in hemodialysis (HD) patients at high risk of
      bleeding remains an intractable problem. Simulating endothelial cells by
      releasing anticoagulant on the membrane may be a promising alternative. METHODS:
      We modified a polyacrylonitrile (PAN) dialyzer by loading argatroban into its
      membrane and verified its anticoagulation efficiency and its influence on
      coagulation markers such as activated partial thromboplastin time (aPTT), D-dimer
      and thrombin-antithrombin complex (TAT) in an animal HD model. RESULTS: All HD
      sessions with the argatroban dialyzer were completed successfully with either no
      or minimal fiber clotting. D-dimer was lower in the argatroban group than in the
      PAN group; TAT and aPTT values were similar in the two groups, which suggests
      better anticoagulation and a similar influence on the coagulation system.
      CONCLUSION: HD with the argatroban dialyzer is feasible, safe and simple, and
      could be used in patients at high risk of bleeding.

PMID- 22652562
TI  - Amphetamines, the pregnant woman and her children: a review.
AB  - The objective of this study is to review and summarize available evidence
      regarding the impact of amphetamines on pregnancy, the newborn infant and the
      child. Amphetamines are neurostimulants and neurotoxins that are some of the most
      widely abused illicit drugs in the world. Users are at high risk of psychiatric
      co-morbidities, and evidence suggests that perinatal amphetamine exposure is
      associated with poor pregnancy outcomes, but data is confounded by other adverse
      factors associated with drug-dependency. Data sources are Government data,
      published articles, conference abstracts and book chapters. The global incidence
      of perinatal amphetamine exposure is most likely severely underestimated but
      acknowledged to be increasing rapidly, whereas exposure to other drugs, for
      example, heroin, is decreasing. Mothers known to be using amphetamines are at
      high risk of psychiatric co-morbidity and poorer obstetric outcomes, but their
      infants may escape detection, because the signs of withdrawal are usually less
      pronounced than opiate-exposed infants. There is little evidence of amphetamine
      induced neurotoxicity and long-term neurodevelopmental impact, as data is scarce
      and difficult to extricate from the influence of other factors associated with
      children living in households where one or more parent uses drugs in terms of
      poverty and neglect. Perinatal amphetamine-exposure is an increasing worldwide
      concern, but robust research, especially for childhood outcomes, remains scarce.
      We suggest that exposed children may be at risk of ongoing developmental and
      behavioral impediment, and recommend that efforts be made to improve early
      detection of perinatal exposure and to increase provision of early-intervention
      services for affected children and their families.

PMID- 22652561
TI  - Does aggressive phototherapy increase mortality while decreasing profound
      impairment among the smallest and sickest newborns?
AB  - OBJECTIVE: Aggressive phototherapy (AgPT) is widely used and assumed to be safe
      and effective for even the most immature infants. We assessed whether the
      benefits and hazards for the smallest and sickest infants differed from those for
      other extremely low-birth-weight (ELBW; <= 1000 g) infants in our Neonatal
      Research Network trial, the only large trial of AgPT. STUDY DESIGN: ELBW infants
      (n=1974) were randomized to AgPT or conservative phototherapy at age 12 to 36 h.
      The effect of AgPT on outcomes (death, impairment, profound impairment, death or
      impairment (primary outcome), and death or profound impairment) at 18 to 22
      months of corrected age was related to BW stratum (501 to 750 g; 751 to 1000 g)
      and baseline severity of illness using multilevel regression equations. The
      probability of benefit and of harm was directly assessed with Bayesian analyses.
      RESULT: Baseline illness severity was well characterized using mechanical
      ventilation and FiO(2) at 24 h age. Among mechanically ventilated infants <= 750
      g BW (n=684), a reduction in impairment and in profound impairment was offset by
      higher mortality (P for interaction <0.05) with no significant effect on
      composite outcomes. Conservative Bayesian analyses of this subgroup identified a
      99% (posterior) probability that AgPT increased mortality, a 97% probability that
      AgPT reduced impairment, and a 99% probability that AgPT reduced profound
      impairment. CONCLUSION: Findings from the only large trial of AgPT suggest that
      AgPT may increase mortality while reducing impairment and profound impairment
      among the smallest and sickest infants. New approaches to reduce their serum
      bilirubin need development and rigorous testing.

PMID- 22652563
TI  - Significance of neonatal body indices in identifying fetal macrosomia.
AB  - OBJECTIVE: To explore the significance of neonatal body indices in identifying
      macrosomic infants, we compared the neonatal birth weight, body length, head
      circumference, chest circumference, neonatal body indices, Quetelet index (QI),
      Kaup Index (KI), head circumference to chest circumference ratio (HC/CC) and
      maternal fasting blood glucose (BG) for both diabetic and healthy mothers. STUDY
      DESIGN: This is a retrospective study of 177 macrosomic neonates, 100 having been
      born to normal mothers and 77 to diabetic mothers. Multiple regression analyses
      were done between neonatal body indices and maternal fasting BG. RESULT: Fetal QI
      and KI indices of macrosomic infants of diabetic mothers were higher compared
      with those born to healthy mothers, whereas the HC/CC was the reverse. The
      multiple regression equation used to compare neonatal physical development
      indices to maternal fasting BG was BG=6.959+0.031QI-(4.482 * HC/CC). QI and HC/CC
      had linear relationships to maternal fasting BG (P<0.05). As birth weight had no
      direct correlation with maternal fasting BG, it was not introduced into the
      regression equation. CONCLUSION: Higher QI and KI along with lower HC/CC may be a
      predictor of macrosomia due to maternal diabetes when compared with birth weight
      alone.

PMID- 22652564
TI  - Fabrication of high-density In(3)Sb(1)Te(2) phase change nanoarray on glass
      fabric reinforced flexible substrate.
AB  - Mushroom-shaped phase change memory (PCM) consisting of a Cr/In(3)Sb(1)Te(2)
      (IST)/TiN (bottom electrode) nanoarray was fabricated via block copolymer
      lithography and single-step dry etching with a gas mixture of Ar/Cl(2). The
      process was performed on a high performance transparent glass-fabric reinforced
      composite film (GFR Hybrimer) suitable for use as a novel substrate for flexible
      devices. The use of GFR Hybrimer with low thermal expansion and flat surfaces
      enabled successful nanoscale patterning of functional phase change materials on
      flexible substrates. Block copolymer lithography employing asymmetrical block
      copolymer blends with hexagonal cylindrical self-assembled morphologies resulted
      in the creation of hexagonal nanoscale PCM cell arrays with an areal density of
      approximately 176 Gb/in(2).

PMID- 22652565
TI  - A search for predictive factors for hypersensitivity reactions to paclitaxel and
      platinum salts in chemotherapy for gynecologic pelvic neoplasms.
AB  - AIMS: To investigate the frequency of and predictive factors for hypersensitivity
      reactions (HR) to taxanes and platinum salts in a cohort of patients treated for
      pelvic gynecologic malignancies. METHODS: The medical records of all patients
      with gynecologic pelvic neoplasms treated with chemotherapy at the Department of
      Gynecologic Oncology, AO Mauriziano Umberto I of Turin, from September 2007
      through August 2008, were retrospectively reviewed. Two multivariate models,
      regarding carboplatin and taxane chemotherapy, respectively, were performed to
      evaluate the potential predictive value of various clinical features. RESULTS:
      The incidence of HR was 14% (22/157). Multivariate models showed that menopausal
      women had a significantly lower probability of HR (OR 0.12, CI 0.02-1.13, p =
      0.06 for the carboplatin model and OR 0.05, CI 0.01-0.63, p = 0.02 for the taxane
      model) while a history of systemic hypersensitivity was associated with a higher
      but non-significant risk of HR (OR 2.64, CI 0.78-8.95, p = 0.11, for the
      carboplatin model and OR 3.42, CI 0.94-12.45, p = 0.06, for the taxane model).
      CONCLUSION: We confirmed a history of hypersensitivity as a risk factor for HR.
      Other larger cohorts should be analyzed: we need to find new predictive factors
      in order to select women who should be submitted to experimental prophylactic
      strategies.

PMID- 22652567
TI  - Rapidly assessing changes in bone mineral balance using natural stable calcium
      isotopes.
AB  - The ability to rapidly detect changes in bone mineral balance (BMB) would be of
      great value in the early diagnosis and evaluation of therapies for metabolic bone
      diseases such as osteoporosis and some cancers. However, measurements of BMB are
      hampered by difficulties with using biochemical markers to quantify the relative
      rates of bone resorption and formation and the need to wait months to years for
      altered BMB to produce changes in bone mineral density large enough to resolve by
      X-ray densitometry. We show here that, in humans, the natural abundances of Ca
      isotopes in urine change rapidly in response to changes in BMB. In a bed rest
      experiment, use of high-precision isotope ratio MS allowed the onset of bone loss
      to be detected in Ca isotope data after about 1 wk, long before bone mineral
      density has changed enough to be detectable with densitometry. The physiological
      basis of the relationship between Ca isotopes and BMB is sufficiently understood
      to allow quantitative translation of changes in Ca isotope abundances to changes
      in bone mineral density using a simple model. The rate of change of bone mineral
      density inferred from Ca isotopes is consistent with the rate observed by
      densitometry in long-term bed rest studies. Ca isotopic analysis provides a
      powerful way to monitor bone loss, potentially making it possible to diagnose
      metabolic bone disease and track the impact of treatments more effectively than
      is currently possible.

PMID- 22652566
TI  - Imatinib resistance and microcytic erythrocytosis in a KitV558Delta;T669I/+
      gatekeeper-mutant mouse model of gastrointestinal stromal tumor.
AB  - Most gastrointestinal stromal tumors (GISTs) harbor a gain-of-function mutation
      in the Kit receptor. GIST patients treated with the tyrosine kinase inhibitor
      imatinib frequently develop imatinib resistance as a result of second-site Kit
      mutations. To investigate the consequences of second-site Kit mutations on GIST
      development and imatinib sensitivity, we engineered a mouse model carrying in the
      endogenous Kit locus both the Kit(V558Delta) mutation found in a familial case of
      GIST and the Kit(T669I) (human KIT(T670I)) "gatekeeper" mutation found in
      imatinib-resistant GIST patients. Similar to Kit(V558/+) mice, Kit(V558;T669I/+)
      mice developed gastric and colonic interstitial cell of Cajal hyperplasia as well
      as cecal GIST. In contrast to the single-mutant Kit(V558/+) control mice,
      treatment of the Kit(V558;T669I/+) mice with either imatinib or dasatinib failed
      to inhibit oncogenic Kit signaling and GIST growth. However, this resistance
      could be overcome by treatment of Kit(V558;T669I/+) mice with sunitinib or
      sorafenib. Although tumor lesions were smaller in Kit(V558;T669I/+) mice than in
      single-mutant mice, both interstitial cell of Cajal hyperplasia and mast cell
      hyperplasia were exacerbated in Kit(V558;T669I/+) mice. Strikingly, the
      Kit(V558;T669I/+) mice developed a pronounced polycythemia vera-like
      erythrocytosis in conjunction with microcytosis. This mouse model should be
      useful for preclinical studies of drug candidates designed to overcome imatinib
      resistance in GIST and to investigate the consequences of oncogenic KIT signaling
      in hematopoietic as well as other cell lineages.

PMID- 22652569
TI  - Radar observations of individual rain drops in the free atmosphere.
AB  - Atmospheric remote sensing has played a pivotal role in the increasingly
      sophisticated representation of clouds in the numerical models used to assess
      global and regional climate change. This has been accomplished because the
      underlying bulk cloud properties can be derived from a statistical analysis of
      the returned microwave signals scattered by a diverse ensemble comprised of
      numerous cloud hydrometeors. A new Doppler radar, previously used to track small
      debris particles shed from the NASA space shuttle during launch, is shown to also
      have the capacity to detect individual cloud hydrometeors in the free atmosphere.
      Similar to the traces left behind on film by subatomic particles, larger cloud
      particles were observed to leave a well-defined radar signature (or streak),
      which could be analyzed to infer the underlying particle properties. We examine
      the unique radar and environmental conditions leading to the formation of the
      radar streaks and develop a theoretical framework which reveals the regulating
      role of the background radar reflectivity on their observed characteristics. This
      main expectation from theory is examined through an analysis of the drop
      properties inferred from radar and in situ aircraft measurements obtained in two
      contrasting regions of an observed multicellular storm system. The observations
      are placed in context of the parent storm circulation through the use of the
      radar's unique high-resolution waveforms, which allow the bulk and individual
      hydrometeor properties to be inferred at the same time.

PMID- 22652568
TI  - Influence of cobalamin scarcity on diatom molecular physiology and identification
      of a cobalamin acquisition protein.
AB  - Diatoms are responsible for ~40% of marine primary production and are key players
      in global carbon cycling. There is mounting evidence that diatom growth is
      influenced by cobalamin (vitamin B(12)) availability. This cobalt-containing
      micronutrient is only produced by some bacteria and archaea but is required by
      many diatoms and other eukaryotic phytoplankton. Despite its potential
      importance, little is known about mechanisms of cobalamin acquisition in diatoms
      or the impact of cobalamin scarcity on diatom molecular physiology. Proteomic
      profiling and RNA-sequencing transcriptomic analysis of the cultured diatoms
      Phaeodactylum tricornutum and Thalassiosira pseudonana revealed three distinct
      strategies used by diatoms to cope with low cobalamin: increased cobalamin
      acquisition machinery, decreased cobalamin demand, and management of reduced
      methionine synthase activity through changes in folate and S-adenosyl methionine
      metabolism. One previously uncharacterized protein, cobalamin acquisition protein
      1 (CBA1), was up to 160-fold more abundant under low cobalamin availability in
      both diatoms. Autologous overexpression of CBA1 revealed association with the
      outside of the cell and likely endoplasmic reticulum localization. Cobalamin
      uptake rates were elevated in strains overexpressing CBA1, directly linking this
      protein to cobalamin acquisition. CBA1 is unlike characterized cobalamin
      acquisition proteins and is the only currently identified algal protein known to
      be implicated in cobalamin uptake. The abundance and widespread distribution of
      transcripts encoding CBA1 in environmental samples suggests that cobalamin is an
      important nutritional factor for phytoplankton. Future study of CBA1 and other
      molecular signatures of cobalamin scarcity identified here will yield insight
      into the evolution of cobalamin utilization and facilitate monitoring of
      cobalamin starvation in oceanic diatom communities.

PMID- 22652570
TI  - Folding pathways of proteins with increasing degree of sequence identities but
      different structure and function.
AB  - Much experimental work has been devoted in comparing the folding behavior of
      proteins sharing the same fold but different sequence. The recent design of
      proteins displaying very high sequence identities but different 3D structure
      allows the unique opportunity to address the protein-folding problem from a
      complementary perspective. Here we explored by Phi-value analysis the pathways of
      folding of three different heteromorphic pairs, displaying increasingly high
      sequence identity (namely, 30%, 77%, and 88%), but different structures called
      G(A) (a 3-alpha helix fold) and G(B) (an alpha/beta fold). The analysis, based on
      132 site-directed mutants, is fully consistent with the idea that protein
      topology is committed very early along the pathway of folding. Furthermore, data
      reveals that when folding approaches a perfect two-state scenario, as in the case
      of the G(A) domains, the structural features of the transition state appear very
      robust to changes in sequence composition. On the other hand, when folding is
      more complex and multistate, as for the G(B)s, there are alternative nuclei or
      accessible pathways that can be alternatively stabilized by altering the primary
      structure. The implications of our results in the light of previous work on the
      folding of different members belonging to the same protein family are discussed.

PMID- 22652572
TI  - Homologation and functionalization of carbon monoxide by a recyclable uranium
      complex.
AB  - Carbon monoxide (CO) is in principle an excellent resource from which to produce
      industrial hydrocarbon feedstocks as alternatives to crude oil; however, CO has
      proven remarkably resistant to selective homologation, and the few complexes that
      can effect this transformation cannot be recycled because liberation of the
      homologated product destroys the complexes or they are substitutionally inert.
      Here, we show that under mild conditions a simple triamidoamine uranium(III)
      complex can reductively homologate CO and be recycled for reuse. Following
      treatment with organosilyl halides, bis(organosiloxy)acetylenes, which readily
      convert to furanones, are produced, and this was confirmed by the use of
      isotopically (13)C-labeled CO. The precursor to the triamido uranium(III) complex
      is formed concomitantly. These findings establish that, under appropriate
      conditions, uranium(III) can mediate a complete synthetic cycle for the
      homologation of CO to higher derivatives. This work may prove useful in spurring
      wider efforts in CO homologation, and the simplicity of this system suggests that
      catalytic CO functionalization may soon be within reach.

PMID- 22652573
TI  - Kinetic and structural studies, origins of selectivity, and interfacial charge
      transfer in the artificial photosynthesis of CO.
AB  - The effective design of an artificial photosynthetic system entails the
      optimization of several important interactions. Herein we report stopped-flow UV
      visible (UV-vis) spectroscopy, X-ray crystallographic, density functional theory
      (DFT), and electrochemical kinetic studies of the Re(bipy-tBu)(CO)(3)(L) catalyst
      for the reduction of CO(2) to CO. A remarkable selectivity for CO(2) over H(+)
      was observed by stopped-flow UV-vis spectroscopy of [Re(bipy-tBu)(CO)(3)](-1).
      The reaction with CO(2) is about 25 times faster than the reaction with water or
      methanol at the same concentrations. X-ray crystallography and DFT studies of the
      doubly reduced anionic species suggest that the highest occupied molecular
      orbital (HOMO) has mixed metal-ligand character rather than being purely doubly
      occupied d(z)(2), which is believed to determine selectivity by favoring CO(2)
      (sigma + pi) over H(+) (sigma only) binding. Electrocatalytic studies performed
      with the addition of Bronsted acids reveal a primary H/D kinetic isotope effect,
      indicating that transfer of protons to Re -CO(2) is involved in the rate limiting
      step. Lastly, the effects of electrode surface modification on interfacial
      electron transfer between a semiconductor and catalyst were investigated and
      found to affect the observed current densities for catalysis more than threefold,
      indicating that the properties of the electrode surface need to be addressed when
      developing a homogeneous artificial photosynthetic system.

PMID- 22652574
TI  - Synthesis of electroactive multinuclear dipyrrinato complexes and Fe(III)
      assisted formation of alpha-alkoxy substituted 5-ferrocenyldipyrromethenes.
AB  - The synthesis and characterization of multinuclear complexes [Pd(acac)(fcdpm)]
      (1), [Pd(fcdpm)(2)] (2), [Co(acac)(fcdpm)(2)] (3), [Co(fcdpm)(3)] (4) and alpha
      alkoxy derivatives [alpha-OMe-fcdpm] (5), [alpha-OEt-fcdpm] (6), [alpha-OPr(n)
      fcdpm] (7) and [alpha-OBu(n)-fcdpm] (8) (fcdpm = 5-ferrocenyldipyrromethene; acac
      = acetylacetone) have been described. Formation of alkoxy derivatives 5-8 takes
      place from highly selective Fe(III) mediated alkoxylation of fcdpm in alcohol. It
      has been established that yield of alpha-alkoxy derivatives depend on the alcohol
      chain length. The compounds under study have been characterized by elemental
      analyses, spectral (IR, (1)H, (13)C NMR, ESI-MS, UV-vis) and electrochemical
      studies (CV and DPV). Structures of 1, 3 and 5 have been verified by X-ray single
      crystal analyses. Structural studies revealed distorted square planar and
      octahedral geometry about Pd(II) and Co(III) centres. All the compounds exhibited
      oxidation wave due to Fc/Fc(+) redox couple (0.34-0.36, 1-4; 0.24-0.25 V, 5-8).

PMID- 22652575
TI  - Identifying competencies in vulvar disorder management for medical students and
      residents: a survey of US vulvar disorder experts.
AB  - OBJECTIVE: The study aimed to perform a content validation process by surveying
      vulvar disorder experts to identify evidence-based competencies appropriate for
      use in developing vulvar curricula for medical trainees. MATERIALS AND METHODS:
      We identified 65 potential vulvar disorder competencies from literature review
      and expert opinions. Survey participants rated these competencies from 1 (not at
      all important) to 4 (highly important) in the training of 3 different groups of
      learners as follows: medical students, obstetrics and gynecology residents, and
      dermatology residents. We administered the survey to all US-based clinical
      members of the International Society for the Study of Vulvovaginal Disease as of
      September 2008 (n = 90). The content validity index and asymmetric CI were
      calculated for each curricular competency for each group of learners separately
      and used to identify competencies for use in curricula development. RESULTS:
      Forty-seven surveys were returned, yielding a response rate of 52.2%.
      Obstetrician-gynecologists represented 66% of the study sample, followed by
      dermatologists (15%), and nurse practitioners (9%). Seventy-nine percent of
      experts received their training by self-teaching, which included mentored
      experiences (62%) and attending conferences or courses (62%). Only 19% received
      vulvar training during residency and 11% during fellowship. Four curricular
      competencies met content validity criteria for medical students, 60 competencies
      for obstetrics and gynecology residents, and 47 competencies for dermatology
      residents. The differences between the 2 groups of residents focused on
      vulvovaginal pain and infection, examination, and procedures of the vagina.
      CONCLUSIONS: The competencies identified in this study can aid in the development
      of targeted curricula for medical students, obstetrics and gynecology residents,
      and dermatology residents.

PMID- 22652576
TI  - Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar
      intraepithelial neoplasia 3 in the United States before vaccine introduction.
AB  - OBJECTIVE: The study aimed to determine the baseline prevalence of human
      papillomavirus (HPV) types in invasive vulvar cancer (IVC) and vulvar
      intraepithelial neoplasia 3 (VIN 3) cases using data from 7 US cancer registries.
      MATERIALS AND METHODS: Registries identified eligible cases diagnosed in 1994 to
      2005 and requested pathology laboratories to prepare 1 representative block for
      HPV testing on those selected. Hematoxylin-eosin-stained sections preceding and
      following those used for extraction were reviewed to confirm representation.
      Human papillomavirus was detected using L1 consensus polymerase chain reaction
      (PCR) with PGMY9/11 primers and type-specific hybridization, with retesting of
      samples with negative and inadequate results with SPF10 primers. For IVC, the
      confirmatory hematoxylin-eosin slides were re-evaluated to determine histological
      type. Descriptive analyses were performed to examine distributions of HPV by
      histology and other factors. RESULTS: Human papillomavirus was detected in
      121/176 (68.8%) cases of IVC and 66/68 (97.1%) cases of VIN 3 (p < .0001).
      Patients with IVC and VIN 3 differed by median age (70 vs 55 y, p = .003). Human
      papillomavirus 16 was present in 48.6% of IVC cases and 80.9% of VIN 3 cases;
      other high-risk HPV was present in 19.2% of IVC cases and 13.2% of VIN 3 cases.
      Prevalence of HPV differed by squamous cell carcinoma histological subtype (p <
      .0001) as follows: keratinizing, 49.1% (n = 55); nonkeratinizing, 85.7% (n = 14),
      basaloid, 92.3% (n = 14), warty 78.2% (n = 55), and mixed warty/basaloid, 100% (n
      = 7). CONCLUSIONS: Nearly all cases of VIN 3 and two thirds of IVC cases were
      positive for high-risk HPV. Prevalence of HPV ranged from 49.1% to 100% across
      squamous cell carcinoma histological subtypes. Given the high prevalence of HPV
      in IVC and VIN 3 cases, prophylactic vaccines have the potential to decrease the
      incidence of vulvar neoplasia.

PMID- 22652579
TI  - Preparation and evaluation of antioxidant peptides from ethanol-soluble proteins
      hydrolysate of Sphyrna lewini muscle.
AB  - To get high yield of ethanol-soluble proteins (EP) and the antioxidant peptides
      from Sphyrna lewini muscle, orthogonal experiments (L(9)(3)(4)) were applied to
      optimize the best extraction conditions and enzyme hydrolysis conditions. The
      yield of EP reached 5.903+/-0.053% under the optimum conditions of ethanol
      concentration 90%, solvent to material ratio 20:1, extraction temperature of 40
      degrees C and extraction time of 80min. The antioxidant SEPH (EP hydrolysate of
      S. lewini muscle) was prepared by using papain under the optimum conditions of
      enzymolysis time 2h, total enzyme dose 1.2%, enzymolysis temperature 50 degrees C
      and pH 6, and its DPPH radical scavenging activity reached 21.76+/-0.42% at the
      concentration of 10mg/ml. Two peptides (F42-3 and F42-5) were isolated from SEPH
      by using ultrafiltration, anion-exchange chromatography, gel filtration
      chromatography and RP-HPLC. The structures of F42-3 and F42-5 were identified as
      Trp-Asp-Arg and Pro-Tyr-Phe-Asn-Lys with molecular weights of 475.50Da and
      667.77Da, respectively. F42-3 and F42-5 exhibited good scavenging activity on
      hydroxyl radical (EC(50) 0.15mg/ml and 0.24mg/ml), ABTS radical (EC(50) 0.34mg/ml
      and 0.12mg/ml), and superoxide anion radical (EC(50) 0.09mg/ml and 0.11mg/ml),
      but moderate DPPH radical (EC(50) 3.63mg/ml and 4.11mg/ml). F42-3 and F42-5 were
      also effectively against lipid peroxidation in the model system and peroxyl free
      radical scavenging in beta-carotene linoleic acid assay. Their high activities
      were due to the smaller size and the presence of antioxidative amino acids within
      the peptide sequences.

PMID- 22652578
TI  - Vulvar pyoderma gangrenosum with renal involvement.
AB  - Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis of unknown etiology
      which usually occurs over the lower extremities; however, unusual presentations
      such as that involving the genital region have been described. Extracutaneous
      involvement of PG in the form of sterile neutrophilic infiltrates in various
      organs has infrequently been reported. We hereby describe a case of PG that was
      limited to the vulvar and perianal area in a 37-year-old female, with associated
      renal involvement in the form of a slight increase in the serum creatinine,
      microhematuria of glomerular origin and proteinuria. The patient had a rapid
      response of both her mucocutaneous lesions and renal dysfunction after the
      initiation of systemic steroids. The present case highlights the importance of
      evaluating all patients with PG for extracutaneous disease to avoid potentially
      harmful diagnostic or therapeutic procedures. Two other reasons for interest are
      the localized presentation of disease on the genital region and the presence of
      vascular involvement, albeit without signs of true vasculitis, vascular changes
      possibly being a histological hallmark of PG involving genitalia.

PMID- 22652580
TI  - Neuromedin B stimulates proliferation of mouse chondrogenic cell line ATDC5.
AB  - Neuromedin B (NMB), which was originally isolated from porcine spinal cord, is a
      mammalian bombesin-related peptide that exerts various physiological effects.
      Previously, we observed expression of NMB in rib cartilage from chicken. Here, we
      report the initial attempt to elucidate the role of NMB in cartilage. We used RT
      PCR to measure the expression of NMB and its receptor (NMB-R) in mouse
      chondrogenic cell line ATDC5. During chondrogenic differentiation of ATDC5 cells,
      NMB mRNA transiently increased on day 4 and then decreased on day 14, whereas NMB
      R mRNA decreased on days 7 and 14. We also characterized immunoreactive NMB in
      ATDC5 culture medium using a combination of specific radioimmunoassay (RIA) and
      reverse phase-high performance liquid chromatography (RP-HPLC). Furthermore,
      using the WST-8 assay, we demonstrated that NMB significantly induced ATDC5
      proliferation; this was inhibited by NMB-R antagonist, BIM 23127. These results
      implicate that NMB is involved in cartilage development, either in an autocrine
      or paracrine manner.

PMID- 22652581
TI  - Interferon responsiveness does not change in treatment-experienced hepatitis C
      subjects: implications for drug development and clinical decisions.
AB  - BACKGROUND: The purpose of this research was to compare interferon (IFN)
      responsiveness in treatment-naive and pegylated interferon alpha-ribavirin (P/R)
      experienced subjects and to understand the implications of comparability in IFN
      responsiveness across treatment courses on drug development and clinical decision
      making. METHODS: Data from 3750 subjects treated with P/R in 8 trials were
      reviewed. The change in hepatitis C virus (HCV) RNA at week 4 in response to P/R
      was compared according to end-of-study (EOS) status (responder, relapser, partial
      and null responder) for treatment-naive subjects and the previous P/R response
      status (known as prior relapsers, prior partial responders, and prior null
      responders at the baseline) for P/R-experienced subjects. RESULTS: In subjects
      receiving a first course of P/R treatment (treatment-naive subjects), HCV RNA
      change after 4 weeks of P/R was correlated with EOS status on a P/R regimen.
      Importantly, for the first time, we have quantitatively demonstrated that IFN
      responsiveness in P/R-experienced subjects administered a second course of P/R
      treatment was similar to the IFN responsiveness in the treatment-naive subjects
      with corresponding EOS status. CONCLUSIONS: We contend that P/R-experienced
      subjects are represented within treatment-naive subjects. There are 2 important
      implications of this finding: (1) from a drug development perspective, a
      successful direct antiviral plus P/R therapy (IFN-based triple therapy) trial in
      P/R-experienced subjects may serve as supportive evidence in treatment-naive
      subjects; and (2) from a clinical decision perspective, previous P/R exposure
      should not alter new treatment decisions involving IFN-based triple therapy, as
      the IFN responsiveness to a second course of IFN is comparable.

PMID- 22652583
TI  - Correlation of spectroscopically determined ligand donor strength and
      nucleophilicity of substituted pyrazoles.
AB  - The relative ligand donor strengths of 10 pyrazole-derived ligands has been
      determined with great accuracy, making use of the interdependence between the
      donor strength of the co-ligand and the (13)C NMR chemical shift of the (i)Pr(2)
      bimy carbene signal in trans-[PdBr(2)((i)Pr(2)-bimy)L] complexes ((i)Pr(2)-bimy =
      1,3-diisopropylbenzimidazolin-2-ylidene; L = pyrazole-derived ligand). Even
      subtle variations in the substitution pattern of the pyrazole backbone up to
      three bonds away from the coordinating nitrogen could be detected reliably using
      this methodology. Alkylation experiments conducted on the pyrazoles using
      electrophiles of varied reactivity (ethyl bromide, ethyl iodide, and
      trimethyloxonium tetrafluoroborate) served as a benchmark to rank the pyrazoles
      in three groups of gradually increasing nucleophilicity, which correlated well
      with their determined donor strength.

PMID- 22652582
TI  - Long-term comparative immunogenicity of protein conjugate and free polysaccharide
      pneumococcal vaccines in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23)
      protects against invasive disease in young healthy persons, randomized controlled
      trials in chronic obstructive pulmonary disease (COPD) have demonstrated no
      benefit in the intention-to-treat population. We previously reported that the 7
      valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe
      and induced greater serotype-specific immunoglobulin G (IgG) and functional
      antibody than did PPSV23 1 month after vaccination. We hypothesized that these
      advantages would persist at 1 and 2 years. METHODS: One hundred eighty-one
      patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90)
      or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay
      and assessed functional antibody activity by a standardized opsonophagocytosis
      assay, reported as a killing index (OPK). We determined differences in IgG and
      OPK between vaccine groups at 1 and 2 years. RESULTS: Relative to PPSV23, PCV7
      induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This
      response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2
      years. Comparable differences in IgG were observed but were less often
      statistically significant. Despite meeting Centers for Disease Control and
      Prevention criteria for PPSV23 administration, almost 50% of individuals had
      never been vaccinated. No differences in the frequency of acute exacerbations,
      pneumonia, or hospitalization were observed. CONCLUSIONS: PCV7 induces a greater
      functional antibody response than PPSV23 in patients with COPD that persists for
      2 years after vaccination. This superior functional response supports testing of
      conjugate vaccination in studies examining clinical end points. CLINICAL TRIALS
      REGISTRATION: NCT00457977.

PMID- 22652586
TI  - Impact of maternal allergy and use of probiotics during pregnancy on breast milk
      cytokines and food antibodies and development of allergy in children until 5
      years.
AB  - BACKGROUND: Whether breast milk (BM) can protect against allergy has been studied
      extensively, with conflicting results. Variations in mothers' BM composition may
      explain some of the conflicting results. Our aim was to assess the impact of
      maternal allergy and probiotic intervention on BM food antibodies, transforming
      growth factor (TGF)-beta(2) and interleukin (IL)-10 and their impact on allergy
      development in children until the ages of 2 and 5. METHODS: We measured total
      IgA, IgA antibodies to cow's milk (CM), casein, beta-lactoglobulin and ovalbumin
      (OVA), TGF-beta(2) and IL-10 in 364 colostrum samples and 321 BM samples taken at
      3 months from mothers participating in a prospective study evaluating the allergy
      preventive effect of probiotics in a cohort with an increased risk for allergy.
      RESULTS: CM, casein and OVA antibodies, TGF-beta(2) and IL-10 were detectable in
      most samples. Maternal allergy was associated with raised levels of IgA to casein
      (p = 0.04) and lower levels of TGF-beta(2) (p = 0.006) in mature BM. Probiotic
      supplementation was associated with increased IL-10 (p = 0.046) and decreased
      casein IgA antibodies (p = 0.027) in mature BM. High OVA IgA antibodies in
      colostrum were associated with the development of atopy by the age of 2, while
      low levels in mature BM were a significant risk factor for the development of
      eczema by the age of 2. TGF-beta(2) levels in BM constituted a risk for
      development of allergy by the age of 2. CONCLUSIONS: The immunologic composition
      of BM was only slightly affected by maternal atopy and could be altered by
      probiotic supplementation. Small effects of BM components on allergy development
      in children were evident.

PMID- 22652588
TI  - Fractional crystallization of oil droplets in O/W emulsions dispersed by
      Synperonic F127.
AB  - The aim of this works is to study an oil-in-water emulsion stabilized with a
      triblock copolymer Synperonic F127 which presents a double size distribution of
      oil droplets. The emulsions were studied experimentally by means of differential
      scanning calorimetry (DSC) and dynamic light scattering (DLS). The DSC analysis
      was carried out focusing on the cooling behavior of the emulsion. The cooling
      thermograms of the oil-in-water emulsion revealed two crystallization peaks with
      Gaussian profile; the interesting characteristic is that both peaks are separated
      in temperature. In accordance to previous works for a single oil dispersed within
      an aqueous phase, the DSC technique must show a single Gaussian peak of
      crystallization attributable to a size distribution of droplets. In the present
      case of emulsions stabilized with 1 g/L of Synperonic F127, the aggregation
      behavior of triblock as a function of temperature allows to produce an emulsion
      with a double size droplet distribution. Comparison with emulsions stabilized
      with 2 and 4 wt% of non-ionic Tween 20 are also presented.

PMID- 22652589
TI  - An improved convective self-assembly method for the fabrication of binary
      colloidal crystals and inverse structures.
AB  - We report an improved convective self-assembly method for the fabrication of
      highly ordered, crack-free binary colloidal crystals (BCCs) and the associated
      inverse structures in large domains at length scales of several centimeters. With
      this method, BCCs can be fabricated in a non-close packed pattern and binary
      inverse opal films can be obtained over a centimeter scale. The presence of
      tetraethyl orthosilicate (TEOS) sol in the self-assembly system was found to play
      a significant role in the resultant structures. The pseudostop band positions are
      adjustable via varying the number ratio of small to large polystyrene (PS)
      spheres. At a given TEOS-to-PS ratio, the binary inverse opal film thickness was
      controllable by varying the colloidal volume fraction with an upper thickness
      threshold (>16 layers).

PMID- 22652590
TI  - Facile fabrication of a superhydrophobic fabric with mechanical stability and
      easy-repairability.
AB  - The poor mechanical stability of superhydrophobic fabrics severely hindered their
      use in practical applications. Herein, to address this problem, we fabricated a
      superhydrophobic fabric with both mechanical stability and easy-repairability by
      a simple method. The mechanical durability of the obtained superhydrophobic
      fabric was evaluated by finger touching and abrasion with sandpaper. The results
      show that rough surface textures of the fabric were retained, and the fabric
      surface still exhibited superhydrophobicity after tests. More importantly, when
      the fabric lost its superhydrophobicity after a long-time abrasion, it can be
      easily rendered with superhydrophobicity once more by a regeneration process.

PMID- 22652591
TI  - Bio-inspired catechol chemistry for electrophoretic nanotechnology of oxide
      films.
AB  - Bio-inspired chemical approach has been developed for the surface modification
      and electrophoretic deposition of manganese dioxide and zirconia nanoparticles,
      prepared by chemical precipitation methods. Caffeic acid, trans-cinnamic acid, p
      coumaric acid, and 2,4-dihydroxycinnamic acid were investigated for the surface
      modification of the nanoparticles. The influence of the structure of the organic
      molecules on their adsorption on the oxide nanoparticles has been investigated.
      The mechanism of caffeic acid adsorption was similar to that of natural
      catecholic amino acid, L-3,4-dihydroxyphenylalanine. The use of caffeic acid
      allowed for agglomerate-free synthesis, efficient dispersion, charging,
      electrophoretic deposition and co-deposition of manganese dioxide and zirconia
      nanoparticles. The deposition yield data, coupled with the results of
      thermogravimetric analysis, X-ray diffraction analysis, and Fourier transform
      infrared spectroscopy, showed that surface chemistry, rather than the crystal
      structure, determined the adsorption behavior. Electron microscopy and energy
      dispersive spectroscopy investigations showed the formation of nanostructured
      oxide films and composites. The deposit composition can be varied.

PMID- 22652592
TI  - Autophagic cell death exists.
AB  - The term autophagic cell death (ACD) initially referred to cell death with
      greatly enhanced autophagy, but is increasingly used to imply a death-mediating
      role of autophagy, as shown by a protective effect of autophagy inhibition. In
      addition, many authors require that autophagic cell death must not involve
      apoptosis or necrosis. Adopting these new and restrictive criteria, and
      emphasizing their own failure to protect human osteosarcoma cells by autophagy
      inhibition, the authors of a recent Editor's Corner article in this journal
      argued for the extreme rarity or nonexistence of autophagic cell death. We here
      maintain that, even with the more stringent recent criteria, autophagic cell
      death exists in several situations, some of which were ignored by the Editor's
      Corner authors. We reject their additional criterion that the autophagy in ACD
      must be the agent of ultimate cell dismantlement. And we argue that rapidly
      dividing mammalian cells such as cancer cells are not the most likely situation
      for finding pure ACD.

PMID- 22652595
TI  - Differences between tumor necrosis factor-alpha receptors types 1 and 2 in the
      modulation of spinal glial cell activation and mechanical allodynia in a rat
      sciatic nerve injury model.
AB  - STUDY DESIGN: Immunohistological analysis of spinal glial cells and analysis of
      pain behavior in the rat neuropathic pain model were investigated to clarify the
      function of tumor necrosis factor (TNF)-alpha receptors p55 type 1 and p75 type
      2. OBJECTIVE: Our objective was to investigate changes in hyperalgesia and glial
      cell activation after injection of antibodies to each TNF receptor in a rat
      sciatic nerve injury model. SUMMARY OF BACKGROUND DATA: Recent research has
      revealed that activation of spinal glia plays an important role in radicular and
      neuropathic pain. TNF-alpha is reportedly a modulator for glial cell activation;
      however, the precise relationship between TNF-alpha and its 2 receptors on glial
      cells has not been fully delineated. METHODS: Chronic constriction sciatic nerve
      injury and sham-operated rats were used. Antibodies to p55 or p75 or saline were
      intrathecally injected at the L5 level into rats with chronic constriction
      injury. Mechanical allodynia was examined for 2 weeks. Spinal cords were removed
      for immunohistochemical studies of ionized calcium-binding adaptor molecule 1 or
      glial fibrillary acidic protein. RESULTS: Saline rats showed significantly more
      mechanical allodynia and the number of ionized calcium-binding adaptor molecule 1
      -immunoreactive microglia and glial fibrillary acidic protein--immunoreactive
      astrocytes were significantly increased in the saline rats compared with sham
      operated rats during the 2 weeks. Injection of both antibodies significantly
      reduced pain behavior and anti-p55 caused significantly greater reduction
      compared with anti-p75. The numbers of microglia in both the antibodies groups
      were significantly decreased when compared with the saline group. In addition,
      the anti-p55 antibody suppressed microglial activation more than the anti-p75
      antibody. CONCLUSION: These results indicate that the microglial TNF-alpha p55
      pathway played a more important role than the TNF-alpha p75 pathway in the
      pathogenesis of peripheral nerve injury pain. This suggests that future studies
      seeking to clarify neuropathic pain should target TNF-alpha and p55 receptors in
      microglia.

PMID- 22652593
TI  - Neuroprotective therapy using granulocyte colony-stimulating factor for patients
      with worsening symptoms of thoracic myelopathy: a multicenter prospective
      controlled trial.
AB  - STUDY DESIGN: An open-labeled multicenter prospective controlled clinical trial.
      OBJECTIVE: To confirm the feasibility of granulocyte colony-stimulating factor (G
      CSF) administration for patients with thoracic myelopathy. SUMMARY OF BACKGROUND
      DATA: Although G-CSF is best known as an important cytokine commonly used to
      treat neutropenia, it also has nonhematopoietic functions. Previous experimental
      studies have shown that G-CSF can enhance tissue regeneration of several organs,
      such as the heart and the brain. We previously reported that G-CSF promotes
      functional recovery after spinal cord injury in rodents. On the basis of those
      findings, we started a clinical trial of neuroprotective therapy, using G-CSF for
      patients with worsening symptoms of thoracic myelopathy. METHODS: Patients whose
      Japanese Orthopaedic Association (JOA) score for thoracic myelopathy had
      decreased 2 points or more during a recent 1-month period were eligible for
      entry. After giving informed consent, patients were assigned to G-CSF and control
      groups. The G-CSF group (n = 10) received G-CSF 10 MUg/kg per day intravenously
      for 5 consecutive days. The control group (n = 14) received similar treatments as
      the G-CSF group except for G-CSF administration. The primary outcome was JOA
      recovery rate at 1 month after G-CSF administration or initial treatment.
      RESULTS: There was greater improvement in neurological functioning between
      baseline and 1-month follow-up in the G-CSF group (JOA recovery rate: 29.1 +/-
      20.5%) than in the control group (JOA recovery rate: 1.1 +/- 4.2%) (P < 0.01). No
      serious adverse events occurred during or after the G-CSF administration.
      CONCLUSION: The results provide evidence that G-CSF administration caused
      neurological recovery in patients with worsening symptoms of thoracic compression
      myelopathy.

PMID- 22652596
TI  - Patterns of care after magnetic resonance imaging of the spine in primary care.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To examine health care
      services use after a magnetic resonance imaging (MRI) scan of the lumbosacral or
      cervical spine ordered by a primary care physician. SUMMARY OF BACKGROUND DATA:
      The use of MRI of the spine in the primary care setting is increasing, yet little
      is known about the relationship between MRI scan findings and subsequent patterns
      of health care utilization. METHODS: Linkage of records from an audit of
      outpatient MRI scans of the spine performed in Ontario, Canada, to administrative
      databases. RESULTS: Of the 647 patients who had a lumbosacral spine MRI scan
      ordered by a primary care physician, 288 (44.5%) were seen in consultation by an
      orthopedic surgeon or neurosurgeon, and 42 (6.5%) received spine surgery during 3
      years of follow-up. Of the 373 patients who had a cervical spine MRI scan ordered
      by a primary care physician, 164 (44.0%) were seen in consultation by an
      orthopedic surgeon or neurosurgeon, and none had spine surgery during 3 years of
      follow-up. Patients with severe disc herniation (likelihood ratio, 5.62, 95%
      confidence interval, 2.64-12.00) or severe spinal stenosis (likelihood ratio,
      2.34; 95% confidence interval, 1.13-4.85) on lumbosacral spine MRI were more
      likely to undergo subsequent surgery. However, many patients with these MRI
      abnormalities did not receive surgery, and the absence of these MRI findings did
      not significantly lower the likelihood of subsequent surgery. CONCLUSION:
      Patients receiving MRI scans of the spine in the primary care setting are
      frequently referred for surgical assessment and most do not receive subsequent
      surgery. MRI scan results do not discriminate very well between those who will
      and will not undergo surgery, suggesting that alternative models for the
      assessment of patients with spinal complaints in primary care should be explored,
      particularly in jurisdictions with long wait times for elective spinal surgery
      consultation.

PMID- 22652597
TI  - Extrahepatic high-density lipoprotein receptor SR-BI and apoA-I protect against
      deep vein thrombosis in mice.
AB  - OBJECTIVE: Deep vein thrombosis (DVT) and pulmonary embolism are frequent causes
      of morbidity and mortality. The goal of our study was to determine whether plasma
      high-density lipoprotein (HDL), which inversely correlates with the risk of
      cardiovascular events, affects DVT. METHODS AND RESULTS: Using a murine DVT model
      of inferior vena cava stenosis, we demonstrated that deficiency of the HDL
      receptor, scavenger receptor class B type I (SR-BI), promotes venous thrombosis.
      As SR-BI(-/-) mice have increased plasma cholesterol levels and abnormal HDL
      particles, we tested SR-BI(-/-) mice with an SR-BI liver transgene that
      normalizes both parameters. These mice also exhibited increased susceptibility to
      DVT, indicating a protective role of extrahepatic SR-BI. Mice lacking the major
      HDL apolipoprotein apoA-I or endothelial nitric oxide synthase (eNOS) (a
      downstream target of endothelial SR-BI signaling) also had a prothrombotic
      phenotype. Intravenous infusion of human apoA-I, an HDL component and SR-BI
      ligend, prevented DVT in wild-type but not SR-BI(-/-) or eNOS(-/-) mice,
      suggesting that its effect is mediated by SR-BI and eNOS. Intravenous apoA-I
      infusion abolished histamine-induced platelet-endothelial interactions, which are
      important for DVT initiation. CONCLUSIONS: An apoA-I (HDL)-SR-BI-eNOS axis is
      highly protective in DVT and may provide new targets for prophylaxis and
      treatment of venous thrombosis.

PMID- 22652598
TI  - Genetic ablation of Adamts13 gene dramatically accelerates the formation of early
      atherosclerosis in a murine model.
AB  - OBJECTIVE: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1
      repeats-13) cleaves von Willebrand factor, thereby modulating thrombosis and
      inflammation. Low plasma ADAMTS13 activity is associated with cardiovascular
      events, including myocardial and cerebral infarction. Here, we investigated the
      role of ADAMTS13 in the development of early atherosclerosis in a murine model.
      METHODS AND RESULTS: Apolipoprotein E-null (ApoE(-/-)) and Adamts13-null
      (Adamts13(-/-)) ApoE(-/-) mice were fed with a high-fat Western diet for 12
      weeks. Atherosclerotic lesions in the aorta and aortic roots were quantified
      after staining. Leukocyte rolling and adhesion onto cremaster venules after
      oxidative injury were determined by intravital microscopy. Although plasma
      cholesterol levels were largely similar in both groups, the extent of
      atherosclerotic lesions in the aorta en face and in the aortic roots in the
      Adamts13(-/-)ApoE(-/-) mice increased ~ 5.5-fold (P=0.0017) and ~ 6.1-fold
      (P=0.0037), respectively. In addition, the ratio of plasma high- to low-molecular
      weight von Willebrand factor multimers increased ~ 3-fold. The leukocyte rolling
      velocities were significantly reduced (P<0.001), with an increased number of
      leukocyte rolling (P=0.0026) and macrophage infiltration into the atherosclerotic
      lesions in the Adamts13(-/-)ApoE(-/-) mice. CONCLUSIONS: Our results suggest that
      ADAMTS13 plays a critical role in modulating the development of early
      atherosclerosis, likely through the proteolytic cleavage of ultra-large von
      Willebrand factor multimers, thereby inhibiting platelet deposition and
      inflammation.

PMID- 22652599
TI  - Fractalkine activates a signal transduction pathway similar to P2Y12 and is
      associated with impaired clopidogrel responsiveness.
AB  - OBJECTIVE: Fractalkine (FKN) activates a G(alphai) protein-coupled signaling
      pathway similar to the one activated by ADP via P2Y(12), which is the drug target
      of clopidogrel. FKN levels are increased under several disease conditions
      associated with impaired clopidogrel responsiveness. METHODS AND RESULTS: Blood
      samples were obtained from healthy volunteers and from 40 patients under chronic
      clopidogrel treatment. FKN reduced prostaglandin E1-induced vasodilator
      stimulated phosphoprotein phosphorylation by ~ 25% (P<0.01) at least partially
      mimicking the effect of ADP via P2Y(12). In vitro, FKN increased platelet
      reactivity index in clopidogrel-treated patients indicating potential activation
      of downstream targets of P2Y(12). When stratifying patients by their FKN levels,
      patients within the highest quartile of FKN (2042 +/- 25 pg/mL) had the weakest
      response to clopidogrel (platelet reactivity index, 68 +/- 4%), and patients
      within the lowest quartile (479 +/- 50 pg/mL) had the strongest response
      (platelet reactivity index, 48 +/- 7%; P=0.0106). FKN by itself induced
      phosphoinositide 3-kinase activation leading to Akt phosphorylation at Ser(473)
      (P<0.01 versus basal). CONCLUSIONS: In addition to desensitizing platelets to
      prostaglandin E1 via G(alphai), FKN induces phosphoinositide 3-kinase-dependent
      Akt phosphorylation via a G(betagamma) protein similar to ADP signaling through
      P2Y(12). FKN increased the platelet ADP response in clopidogrel-treated patients.
      Once released from an atherosclerotic lesion, this mechanism could contribute
      locally to impaired clopidogrel responsiveness at the vulnerable plaque.

PMID- 22652601
TI  - Endothelial cells require related transcription enhancer factor-1 for cell-cell
      connections through the induction of gap junction proteins.
AB  - OBJECTIVE: Capillary network formation represents a specialized endothelial cell
      function and is a prerequisite to establish a continuous vessel lumen. Formation
      of endothelial cell connections that form the vascular structure is regulated, at
      least in part, at the transcriptional level. We report here that related
      transcription enhancer factor-1 (RTEF-1) plays an important role in vascular
      structure formation. METHODS AND RESULTS: Knockdown of RTEF-1 by small
      interfering RNA or blockage of RTEF-1 function by the transcription enhancer
      activators domain decreased endothelial connections in a Matrigel assay, whereas
      overexpression of RTEF-1 in endothelial cells resulted in a significant increase
      in cell connections and aggregation. In a model of oxygen-induced retinopathy,
      endothelial-specific RTEF-1 overexpressing mice had enhanced angiogenic sprouting
      and vascular structure remodeling, resulting in the formation of a denser and
      more highly interconnected superficial capillary plexus. Mechanistic studies
      revealed that RTEF-1 induced the expression of functional gap junction proteins
      including connexin 43, connexin 40, and connexin 37. Blocking connexin 43
      function inhibited RTEF-1-induced endothelial cell connections and aggregation.
      CONCLUSIONS: These findings provide novel insights into the transcriptional
      control of endothelial function in the coordination of cell-cell connections.

PMID- 22652600
TI  - Neutrophil extracellular trap (NET) impact on deep vein thrombosis.
AB  - Deep vein thrombosis (DVT) is a major health problem that requires improved
      prophylaxis and treatment. Inflammatory conditions such as infection, cancer, and
      autoimmune diseases are risk factors for DVT. We and others have recently shown
      that extracellular DNA fibers produced in inflammation and known as neutrophil
      extracellular traps (NETs) contribute to experimental DVT. NETs stimulate
      thrombus formation and coagulation and are abundant in thrombi in animal models
      of DVT. It appears that, in addition to fibrin and von Willebrand factor, NETs
      represent a third thrombus scaffold. Here, we review how NETs stimulate
      thrombosis and discuss known and potential interactions of NETs with endothelium,
      platelets, red blood cells, and coagulation factors and how NETs could influence
      thrombolysis. We propose that drugs that inhibit NET formation or facilitate NET
      degradation may prevent or treat DVT.

PMID- 22652603
TI  - Mast cells induce vascular smooth muscle cell apoptosis via a toll-like receptor
      4 activation pathway.
AB  - OBJECTIVE: Activated mast cells (MCs) release chymase, which can induce vascular
      smooth muscle cell (VSMC) apoptosis leading to plaque destabilization. Because
      the mechanism through which MCs release chymase in atherosclerosis is unknown, we
      studied whether MC-associated VSMC apoptosis is regulated by toll-like receptor 4
      (TLR4) signaling. METHODS AND RESULTS: Local recruitment and activation of MCs
      reduced VSMC content specifically in the cap region of vulnerable plaques in
      apolipoprotein E knockout mice. Cotreatment with the TLR4 antagonist Bartonella
      quintana lipopolysaccharide prevented this VSMC loss, suggesting an important
      role for TLR4 signaling in MC-induced VSMC apoptosis. Coculture of VSMCs with MCs
      activated by the TLR4 agonist Escherichia coli lipopolysaccharide increased VSMC
      apoptosis. Apoptosis was inhibited by TLR4 and chymase blockers, indicating that
      TLR4 signaling is involved in chymase release in MCs. This pathway was mediated
      via interleukin-6 because interleukin-6 promoted MC-associated VSMC apoptosis,
      which was inhibited by blocking chymase release. In addition, TLR4 activation in
      MCs induced interleukin-6 production, which was reduced by preincubation with
      either B. quintana lipopolysaccharide or an anti-TLR4 antibody. CONCLUSIONS: We
      show that MCs promote VSMC apoptosis in vivo. In addition, TLR4 signaling is
      important in chymase release in MCs and, therefore, in plaque destabilization by
      regulating VSMC apoptosis.

PMID- 22652604
TI  - A combined etching process toward robust superhydrophobic SiC surfaces.
AB  - Large-scale porous SiC was fabricated by a combination of Pt-assisted etching and
      reactive ion etching. It was found that the surface roughness of combined
      etchings increased dramatically in comparison with metal-assisted etching or
      reactive ion etching only. To reduce the surface energy, the porous SiC surface
      was functionalized with perfluorooctyl trichlorosilane, resulting in a
      superhydrophobic SiC surface with a contact angle of 169.2 degrees  and a
      hysteresis of 2.4 degrees . The superhydrophobicity of the SiC surface showed a
      good long-term stability in an 85  degrees C/85% humidity chamber. Such
      superhydrophobicity was also stable in acidic or basic solutions, and the pH
      values showed little or no effect on the SiC surface status. In addition,
      enhancement of porosity-induced photoluminescence intensity was found in the
      superhydrophobic SiC samples. The robust superhydrophobic SiC surfaces may have a
      great potential for microfluid device, thermal ground plane, and biosensor
      applications.

PMID- 22652605
TI  - Influence of adsorbed polar molecules on the electronic transport in a composite
      material Li(1.1)V3O8-PMMA for lithium batteries.
AB  - The broadband dielectric spectroscopy (BDS) technique (40 to 10(10) Hz) is used
      here to measure the electronic transport across all observed size scales of a
      Li(1.1)V(3)O(8)-polymer-gel composite material for lithium batteries. Different
      electrical relaxations are evidenced, resulting from the polarizations at the
      different scales of the architecture: (i) atomic lattice (small-polaron hopping),
      (ii) particles, (iii) clusters of particles, and finally (iv) sample-current
      collector interface. A very good agreement with dc-conductivity measurements on a
      single macro-crystal [M. Onoda and I. Amemiya, J. Phys.: Condens. Matter, 2003,
      15, 3079.] shows that the BDS technique does allow probing the bulk (intrinsic)
      electrical properties of a material in the form of a network of particles
      separated by boundaries in a composite. Moreover, this study highlights a
      lowering of the surface electronic conductivity of Li(1.1)V(3)O(8) particles upon
      adsorption of polar ethylene carbonate (EC) and propylene carbonate (PC) that
      trap surface polarons. This result is meaningful as EC and PC are typical
      constituents of a liquid electrolyte of lithium batteries. It is thus suggested
      that interactions between active material particles and the liquid electrolyte
      play a role in the electronic transport within composite electrodes used in a
      lithium battery.

PMID- 22652602
TI  - Selective beta2-adrenoreceptor stimulation attenuates myocardial cell death and
      preserves cardiac function after ischemia-reperfusion injury.
AB  - OBJECTIVE: beta(2)-adrenoreceptor activation has been shown to protect cardiac
      myocytes from cell death. We hypothesized that acute beta(2)-adrenoreceptor
      stimulation, using arformoterol (ARF), would attenuate myocardial
      ischemia/reperfusion (R) injury via NO synthase activation and cause a subsequent
      increase in NO bioavailability. METHODS AND RESULTS: Male C57BL/6J and
      endothelial NO synthase (eNOS) knockout mice were subjected to 45 minutes of
      myocardial ischemia and 24 hours of R. ARF or vehicle was administered 5 minutes
      before R. Serum troponin-I was measured, and infarct size per area-at-risk was
      evaluated at 24 hours of R. Echocardiography was performed at baseline and 2
      weeks after R. Myocardial cAMP, protein kinase A, eNOS/Akt phosphorylation
      status, and NO metabolite levels were assayed. ARF (1 ug/kg) reduced infarct size
      per area-at-risk by 53.1% (P<0.001 versus vehicle) and significantly reduced
      troponin-I levels (P<0.001 versus vehicle). Ejection fraction was significantly
      preserved in ARF-treated hearts compared with vehicle hearts at 2 weeks of R.
      Serum cAMP and nuclear protein kinase A C-alpha increased 5 and 15 minutes after
      ARF injection, respectively (P<0.01). ARF increased Akt phosphorylation at
      Thr(308) (P<0.001) and Ser(473) (P<0.01), and eNOS phosphorylation at Ser(1177)
      (P<0.01). ARF treatment increased heart nitrosothiol levels (P<0.001) at 15 min
      after injection. ARF failed to reduce infarct size in eNOS(-/-) mice.
      CONCLUSIONS: Our results indicate that beta(2)-adrenoreceptor stimulation
      activates cAMP, protein kinase A, Akt, and eNOS and augments NO bioavailability.
      Activation of this prosurvival signaling pathway attenuates myocardial cell death
      and preserves cardiac function after ischemia/reperfusion.

PMID- 22652606
TI  - The VIP syndrome: a clinical study in hospital psychiatry. 1964.

PMID- 22652607
TI  - Rereading Weintraub.

PMID- 22652608
TI  - Special section on DSM-5: nearing the finish line.

PMID- 22652609
TI  - Diagnostic inflation: causes and a suggested cure.
AB  - There have been a striking diagnostic inflation and a corresponding increase in
      the use of psychotropic drugs during the past 30 years. DSM-5, scheduled to
      appear in May 2013, proposes another grand expansion of mental illness. In this
      article, we will review the causes of diagnostic exuberance and associated
      medical treatment. We will then suggest a method of stepped care combined with
      stepped diagnosis, which may reduce overdiagnosis without risking undertreatment
      of those who really need help. The goal is to control diagnostic inflation, to
      reduce the harms and costs of unnecessary treatment, and to save psychiatry from
      overdiagnosis and ridicule.

PMID- 22652610
TI  - Recurrence of depression after bereavement-related depression: evidence for the
      validity of DSM-IV bereavement exclusion from the Epidemiologic Catchment Area
      Study.
AB  - The DSM-IV diagnostic criteria for major depressive disorder exclude bereavement
      related depressive episodes that are brief and lack certain severe symptoms and
      are thus better explained as normal grief responses. However, the DSM-5 Task
      Force proposes to eliminate this exclusion because of a lack of evidence that
      such episodes differ relevantly from standard major depression. Using the two
      wave longitudinal Epidemiologic Catchment Area Study, we compared 1-yr depression
      recurrence rates at wave 2 of four groups at wave 1 baseline: (1) those with no
      history of depressive disorder (n = 18,239), (2) those who had only lifetime
      excludable bereavement-related depression (n = 25), (3) those with brief-episode
      (<= 2 months duration) lifetime standard depressive disorder (n = 446), and (4)
      those with nonbrief lifetime standard depressive disorder (n = 581). The
      recurrence rate in the excludable-depression group (3.7%) was not significantly
      different from the no-history group (1.7%) but was significantly and
      substantially lower than in the brief and nonbrief standard depression groups
      (14.4% and 16.2%, respectively). These findings confirm findings reported by
      Mojtabai (Arch Gen Psychiatry 68:920-928, 2011) using a different data set and
      time frame and thus substantially strengthen the support for the validity of
      bereavement exclusion and for its preservation in the DSM-5.

PMID- 22652611
TI  - DSM-5 further inflates attention deficit hyperactivity disorder.
AB  - Since the publication of DSM-IV in 1994, attention deficit hyperactivity disorder
      (ADHD) prevalence and medication use unexpectedly increased significantly. In
      this article, we explore the DSM-5 proposals for ADHD that are likely to further
      increase its prevalence. We also address the possible harmful consequences of
      further expansion of this already broad, defined, and inflated DSM category.

PMID- 22652612
TI  - Behavioral addiction--quo vadis?
AB  - Behavioral addiction is a new class of psychiatric disorders being considered for
      inclusion in the next edition of the American Psychiatric Association's
      Diagnostic and Statistical Manual of Mental Disorders (DSM-5). In this article,
      pathological model railroading disorder is introduced as a vehicle for
      highlighting and discussing the foreseeable risks and benefits of legitimizing
      behavioral addiction as a diagnostic class in DSM-5.

PMID- 22652613
TI  - Hebephilia and the construction of a fictitious diagnosis.
AB  - As mass media and the advertising industry sexualize children at earlier ages,
      DSM-5 is considering a proposal for a new mental disorder involving sexual
      attraction to adolescents. Despite the fact that most men are sexually aroused by
      pubescent teens, some clinicians and researchers believe they have identified a
      new subgroup of chronically impaired men who are compulsively drawn to older
      children. We discuss the proposal and conclude that it is insufficiently
      documented and that with such potentially serious medicolegal consequences,
      inclusion in the new manual is not advised. Clinically, there are insufficient
      data showing the construct to be reliable and valid. Forensically, a new
      diagnosis of hebephilia is likely to be used to justify indefinite civil
      commitment and other onerous punishments.

PMID- 22652614
TI  - Mixed anxiety depression should not be included in DSM-5.
AB  - Subthreshold anxiety and subthreshold depressive symptoms often co-occur in the
      general population and in primary care. Based on their associated significant
      distress and impairment, a psychiatric classification seems justified. To enable
      classification, mixed anxiety depression (MAD) has been proposed as a new
      diagnostic category in DSM-5. In this report, we discuss arguments against the
      classification of MAD. More research is needed before reifying a new category we
      know so little about. Moreover, we argue that in patients with MAD symptoms and a
      history of an anxiety or depressive disorder, symptoms should be labeled as part
      of the course trajectories of these disorders, rather than calling it a different
      diagnostic entity. In patients with incident co-occurring subthreshold anxiety
      and subthreshold depression, subthreshold categories of both anxiety and
      depression could be classified to maintain a consistent classification system at
      both threshold and subthreshold levels.

PMID- 22652615
TI  - Should prolonged grief be reclassified as a mental disorder in DSM-5?:
      reconsidering the empirical and conceptual arguments for complicated grief
      disorder.
AB  - The proposed changes to DSM-5 will create new categories of mental disorder
      (referred to here generically as Prolonged Grief Disorder'' [PGD]) to diagnose
      individuals experiencing prolonged intense grief reactions to the loss of a loved
      one. Individuals could be diagnosed even if they have no depressive or anxiety
      symptoms but only symptoms typical of grief (e.g., yearning, avoidance of
      reminders, disbelief, feelings of emptiness). The main challenge for such
      proposals is to establish that the proposed diagnostic criteria validly
      discriminate a genuine psychiatric disorder of grief from intense normal grief.
      With this test in mind, I evaluate the soundness of four empirical arguments and
      one conceptual argument that have been put forward to support such proposals: (1)
      PGD has discriminant validity because distinctive, pathognomonic symptoms
      distinguish it from normal grief; (2) PGD has discriminant validity because it
      identifies grief symptoms that are of greater absolute severity than in normal
      grief; (3) PGD has predictive validity because it implies a chronic, interminable
      process of grieving, thus a derailment of the normal process of grief resolution;
      (4) PGD has predictive validity because it predicts negative mental and physical
      health outcomes unlikely in normal grief; and (5) PGD has conceptual validity
      because grief is analogous to a wound or, alternatively, lengthy grief is
      analogous to a wound that does not heal. Upon close examination, each of these
      arguments turns out to have serious empirical or conceptual deficiencies. I
      conclude that the proposed diagnostic criteria for PGD fail to discriminate
      disorder from intense normal grief and are likely to yield massive false-positive
      diagnoses. Consequently, the proposal to add pathological grief categories to DSM
      5 should be withdrawn pending further research to identify more valid criteria
      for diagnosing PGD.

PMID- 22652616
TI  - A critique of the DSM-5 field trials.
AB  - This article provides an overview and critique of the field trials for the
      current revision of the Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition (DSM-5). The purpose of the DSM-5 field trials was to evaluate the
      use, feasibility, safety, reliability, and validity of the DSM-5 proposals. In
      this article, the procedures for evaluating these properties of the DSM-5 are
      reviewed, and several concerns-such as delays, disorganization, missed deadlines,
      field trial cancellations, lack of adequate validity testing, and high clinician
      attrition rates-and their likely impact on the field trial results are presented.

PMID- 22652617
TI  - Comparing the stability of diagnosis in full vs. partial posttraumatic stress
      disorder.
AB  - We studied differences in diagnostic stability between patients with full and
      patients with partial posttraumatic stress disorder (PTSD). We collected self
      reported symptoms of PTSD, anxiety, depression, and functioning at a Veterans
      Affairs mental health clinic (n = 1962). We classified patients as meeting full
      or partial PTSD based upon their initial assessment. We performed Kaplan-Meier
      survival analysis to compare stability of diagnosis over time and Cox
      proportional hazards models to understand how comorbid symptoms and level of
      functioning confounded the relationship. We performed a chart review to examine
      differences in treatment received by the two groups. Patients in the partial PTSD
      group lost their diagnosis significantly faster and at significantly higher rates
      than did patients with full PTSD. Comorbid symptoms contributed significantly to
      this difference. Mental health treatments delivered to the two groups were
      similar. These diagnoses appear to be different, suggesting that people with
      partial PTSD may benefit from a different clinical approach.

PMID- 22652618
TI  - Personality disorder assessments in acute depressive episodes: stability at
      follow-up.
AB  - Assessment of personality disorders during the acute phase of major depression
      may be invalidated by the potential distortion of personality traits in depressed
      mood states. However, few studies have tested this assumption. We examined the
      stability of personality disorder diagnoses during and then after a major
      depressive episode (MDE). Subjects with major depression (N = 82) completed the
      17-item Hamilton Depression Scale (HAM-17) and the Structured Clinical Interview
      for Axis II both at baseline during an MDE and at 3-month follow-up. We compared
      subjects who continued to meet DSM-IV criteria for the same Axis II diagnoses
      with patients whose diagnosis changed and patients with no DSM-IV personality
      disorder to determine the relationship to major depression and its severity.
      Sixty-six percent of subjects met DSM-IV criteria for at least one Axis II
      diagnosis at baseline and 80% had the same personality disorder diagnoses at
      follow-up. Thirty-four percent had a full remission of MDE at 3-month follow-up.
      Instability of Axis II diagnosis was associated with number of Axis II diagnoses
      at baseline (p = .036) and Hispanic ethnicity (p = .013). HAM-17 score change was
      unrelated to differences in the number of symptoms of personality disorders from
      baseline to follow-up, nor was remission from MDE on follow-up. Axis II diagnoses
      in acutely depressed patients reassessed after 3 months are often stable and not
      associated with remission of or improvement in major depression.

PMID- 22652620
TI  - The role of forgiveness in adolescents who engage in nonsuicidal self-injury.
AB  - The present study is an exploratory investigation assessing the role of
      forgiveness of self and forgiveness of others in adolescent nonsuicidal self
      injury (NSSI). Participants included a diverse sample of self-injuring
      adolescents (N = 30). Results indicated that lack of self-forgiveness was
      associated with engaging in NSSI for specific reasons related to the regulation
      of emotions and social functioning, namely to get rid of unwanted emotions, to
      feel something due to feeling numb or empty, and to communicate with others. Lack
      of self-forgiveness was also associated with greater lifetime frequency of NSSI.
      No relationship was found between forgiveness of others and NSSI. The
      implications of these findings are discussed in relation to Dialectical Behavior
      Therapy for NSSI, traditional forgiveness interventions, and treatment of youth
      who engage in NSSI.

PMID- 22652619
TI  - Exposure to antidepressant medications and suicide attempts in adult depressed
      inpatients.
AB  - The effects of antidepressant medication on suicide risk remain unclear. This
      study explores any association between antidepressant medication and suicide
      attempts leading to hospitalization in adult depressed patients.The medical
      records of 103 patients admitted after a suicide attempt were examined and
      compared with those of a matched control group of depressed patients (n = 103)
      admitted without suicide attempts as well as a patient group with and without
      suicide attempts on separate hospitalizations (n = 25). No significant difference
      in antidepressant medication exposure before hospitalization was found between
      groups. Selective serotonin reuptake inhibitor exposure was higher in patients
      with suicide attempts, albeit nonsignificant, but was identical in patients
      admitted on two occasions with and without suicide attempts. The most common
      method for suicide attempt was drug overdose (52.4%). Patients in the group with
      suicide attempts had significantly more past suicide attempts. Study results do
      not confirm any relationship between antidepressants and suicide attempts. Close
      monitoring of depressed patients is advised especially in early treatment.

PMID- 22652621
TI  - Perceptions of parental caretaking in childhood and religiosity/spirituality
      status in adulthood.
AB  - Relationships between parental caretaking quality in childhood and
      religiosity/spirituality in adulthood, which are the focus of the present study,
      have undergone limited study. Using a cross-sectional sample of consecutive
      internal medicine outpatients, we examined in 308 participants three aspects of
      their parenting experience (i.e., number of different caretakers, whether
      caretakers were biological parents or not, perceived quality of parental
      caretaking) and level of religiosity/spirituality over the past 12 months using
      the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being Scale
      (FACIT-Sp-12). Current level of religiosity/spirituality did not correlate with
      the number of different caretakers or whether caretakers were biological parents
      or not. However, 6 of 12 FACIT-Sp-12 scales and the overall FACIT-Sp-12 score
      statistically significantly correlated with perceived quality of parental
      caretaking, with better parenting ratings associated with higher levels of self
      reported religiosity/spirituality. Findings suggest that better parenting in
      childhood is associated with higher levels of certain aspects of current
      religiosity/spirituality in adulthood.

PMID- 22652623
TI  - Electrical nano-imprint lithography.
AB  - We present a novel technique called electrical nano-imprint lithography (e-NIL)
      for topographic and electrostatic patterning of thermoplastic electret films at
      the nanometer scale. This versatile parallel process consists of simultaneously
      transferring micro- or nano-patterns from a conductive mold into a thermoplastic
      electret film and injecting positive or negative electrical charges into the
      bottom of the imprinted patterns. As proof of concept, we used this e-NIL process
      to fabricate arrays of 5 MUm and 300 nm wide topographic charged patterns into
      polymethylmethacrylate (PMMA) thin films coated on silicon wafers. We
      demonstrated that these patterned PMMA films, exhibiting thousands of
      topographically confined and electrostatically active sites, can be used for high
      throughput directed assembly of colloidal nanoparticles.

PMID- 22652622
TI  - Psychiatric treatment of the VIP: some paradoxical risks.
AB  - One might expect that VIPs-individuals with wealth, fame, or power-would
      typically receive excellent care when treated for psychiatric disorders. Often,
      this is the case, but paradoxically, VIP status may compromise the quality of
      psychiatric treatment. In this article, we present four case examples,
      representing disguised amalgamations of actual cases from our experience,
      demonstrating how VIP patients may sometimes receive suboptimal psychiatric care.
      These cases show certain similarities; typically, there was no serious doubt
      about the general nature of the treatment that should be undertaken, but the
      treatment team was unable to deliver that treatment in the usual manner because
      of various outside pressures created by the VIP status of the patient and by the
      patient's entourage. One possible solution to this problem, when feasible, is to
      assign treatment to a team specifically experienced with VIP patients. A strong
      and united treatment team, accustomed to the unusual difficulties and pressures
      often encountered with VIP patients, can be prepared to act promptly, firmly, and
      unanimously to devise an appropriate treatment plan and then maintain this plan
      true to its course despite these pressures.

PMID- 22652624
TI  - microRNA biomarkers in body fluids of prostate cancer patients.
AB  - The abundance of miRNAs - small non-coding RNAs involved in posttranscriptional
      regulation of gene expression - in tissues and body fluids of cancer patients
      hold great promise to identify specific biomarkers, which may be useful for early
      diagnosis as well as to predict the clinical outcome and treatment response. For
      the extraction and quantification of miRNAs from cells and tissues, present
      technologies for transcriptome analyses like microarrays, quantitative real-time
      PCR or next generation sequencing can be applied. However, the analyses of miRNAs
      in body fluids like serum or urine is still a challenge with respect to the
      nucleic acid recovery from very limited sources of biomaterial, normalization
      strategies and validation using independent technologies. The presence of
      specific miRNA patterns in body fluids like serum of cancer patients suggests a
      promising role of these molecules as surrogate markers. However, the majority of
      miRNA studies were addressed in relatively small patient cohorts limiting the
      validity and the clinical application of potential miRNA biomarkers or
      signatures. We reflect the critical steps to translate miRNA biomarker into
      clinical routine diagnostics and present future aspects for the fast, robust and
      standardized quantification of miRNAs in body fluids.

PMID- 22652625
TI  - Hi-C: a comprehensive technique to capture the conformation of genomes.
AB  - We describe a method, Hi-C, to comprehensively detect chromatin interactions in
      the mammalian nucleus. This method is based on Chromosome Conformation Capture,
      in which chromatin is crosslinked with formaldehyde, then digested, and re
      ligated in such a way that only DNA fragments that are covalently linked together
      form ligation products. The ligation products contain the information of not only
      where they originated from in the genomic sequence but also where they reside,
      physically, in the 3D organization of the genome. In Hi-C, a biotin-labeled
      nucleotide is incorporated at the ligation junction, enabling selective
      purification of chimeric DNA ligation junctions followed by deep sequencing. The
      compatibility of Hi-C with next generation sequencing platforms makes it possible
      to detect chromatin interactions on an unprecedented scale. This advance gives Hi
      C the power to both explore the biophysical properties of chromatin as well as
      the implications of chromatin structure for the biological functions of the
      nucleus. A massively parallel survey of chromatin interaction provides the
      previously missing dimension of spatial context to other genomic studies. This
      spatial context will provide a new perspective to studies of chromatin and its
      role in genome regulation in normal conditions and in disease.

PMID- 22652626
TI  - Computational detection and analysis of sequences with duplex-derived interstrand
      G-quadruplex forming potential.
AB  - Bioinformatic approaches to the identification of genomic sequences having G
      quadruplex forming potential (QFP) has enabled important tests of the structure
      of these sequences in vitro and of their behavior under conditions where the
      formation or function of G-quadruplexes is modulated in vivo. Several similar
      approaches to identifying intramolecular QFP (i.e. forming among G-runs on one
      strand of DNA) have been developed previously, but none appears to perfectly
      predict G-quadruplex formation. Here we describe a new approach, which
      complements and differs from prior approaches in that it identifies motifs
      containing G-runs on both strands of duplex DNA that could contribute to G
      quadruplex structures. We call these motifs duplex-derived interstrand QFP
      (ddiQFP), and illustrate their potential applications by describing their genomic
      distribution and an example of their correspondence to loci targeted by a G
      quadruplex-unwinding DNA helicase in yeast.

PMID- 22652627
TI  - The challenge of gene expression profiling in heterogeneous clinical samples.
AB  - Almost all samples used in tumor biology, such as tissues and bodily fluids, are
      heterogeneous, i.e., consist of different cell types. Evaluating the degree of
      heterogeneity in samples can increase our knowledge on processes such as clonal
      selection and metastasis. In addition, generating expression profiles from
      specific sub populations of cells can reveal their distinct functions. Tissue
      heterogeneity also poses a challenge, as it can confound the interpretation of
      gene expression data. This chapter will (1) give a brief overview on how
      heterogeneity may influence gene expression profiling data and (2) describe the
      methods that are currently available to assess transcriptional biomarkers in a
      heterogeneous cell population.

PMID- 22652629
TI  - Missense polymorphisms within IL-10R1 exons are not associated with systemic
      lupus erythematosus in Chinese.
AB  - OBJECTIVE: Studies have suggested that interleukin-10 receptor1 (IL-10R1) is
      involved in genetic susceptibility to systemic lupus erythematosus (SLE) in
      animal models and Caucasians. Therefore, the current study was designed to
      determine whether the IL-10R1 gene plays a role in the pathogenesis of human SLE
      in the Chinese Han population. METHODS: The seven exons of the IL-10R1 gene were
      amplified and sequenced using a BigDye Terminator v1.1 Cycle Sequencing kit and
      an ABI 3100 DNA Analyzer. A missense single nucleotide polymorphism (SNP) locus
      with a minor allele frequency of at least 0.1 was chosen to evaluate the
      correlation with the incidence of SLE. RESULTS: Seven SNPs were found to reside
      in the exons of the IL-10R1 gene. Among the SNPs, A744G was evaluated for a
      correlation with the incidence of SLE because A744G was the only missense SNP
      with a minor allele frequency of at least 0.1. There was no significant
      difference in the distribution of the A and G alleles between the SLE patient
      group and the healthy control group (P = 0.693). Furthermore, the genotype
      frequencies of A744A, A744G and G744G did not differ significantly between the
      two groups (P = 0.906). CONCLUSION: In the Chinese Han population, missense SNPs
      within the exons of the IL-10R1 gene do not contribute to the development of SLE.

PMID- 22652628
TI  - Impaired osteogenic differentiation of mesenchymal stem cells derived from
      multiple myeloma patients is associated with a blockade in the deactivation of
      the Notch signaling pathway.

PMID- 22652630
TI  - Bones, groans, and silicone.

PMID- 22652631
TI  - Serum procalcitonin has negative predictive value for bacterial infection in
      active systemic lupus erythematosus.
AB  - BACKGROUND: Previous studies in systemic lupus erythematosus (SLE) patients have
      produced conflicting results regarding the diagnostic utility of procalcitonin
      (PCT). The aim of this study was to determine predictive values of PCT and C
      reactive protein (CRP) for bacterial infection in SLE patients. MATERIALS AND
      METHODS: This was a cross-sectional study of clinic and hospitalized SLE patients
      with and without bacterial infection recruited over 18 months. Bacterial
      infection was defined as positive culture results. SLE disease activity was
      measured using SLEDAI. PCT and CRP were measured by automated immunoassays.
      RESULTS: Sixty-eight patients (57 females) were studied. Ten patients (15%) had
      infection. The areas under the receiver operating characteristic curves for PCT
      and CRP were not significantly different [0.797 (CI 0.614-0.979) versus 0.755 (CI
      0.600-0.910)]. In lupus flare patients, PCT but not CRP was higher with infection
      (p = 0.019 versus 0.195). A PCT of <0.17 ng/ml ruled out infection with 94%
      negative predictive value (NPV). In remission patients, CRP but not PCT was
      elevated with infection (p = 0.036 versus 0.103). CRP < 0.57 mg/dl had 96% NPV.
      CONCLUSION: PCT may be a better marker to rule out bacterial infection in lupus
      flare but not in remission or general screening.

PMID- 22652632
TI  - Late-onset systemic lupus erythematosus in Northwestern Spain: differences with
      early-onset systemic lupus erythematosus and literature review.
AB  - To further investigate into the epidaemiology of systemic lupus erythematosus
      (SLE) in Southern Europe, we have assessed the incidence, clinical spectrum and
      survival of patients diagnosed with late-onset SLE (age >= 50 years) according to
      the 1982 American College of Rheumatology (ACR) classification criteria at the
      single hospital for a well-defined population of Lugo, Northwestern (NW) Spain.
      Between January 1987 and December 2006, 51 (39.3%) of the 150 patients diagnosed
      as having SLE fulfilled definitions for late-onset SLE. The predominance of women
      among late-onset SLE (4:1) was reduced when compared with that observed in early
      onset SLE (7:1). However, the incidence of late-onset SLE was significantly
      higher in women (4.2 [95% confidence interval (CI): 3.1-5.6] per 100,000
      population) than in men (1.3 [95% CI: 0.6-2.2] per 100,000 population) (p <
      0.001). As observed in early-onset SLE, the most frequent clinical manifestation
      in patients with late-onset SLE was arthritis (71.2%). Renal disease was less
      common in late-onset SLE (13.5%) than in early-onset SLE (26.4%); p = 0.07). In
      contrast, secondary Sjogren syndrome was more commonly found in the older age
      group (27.1% versus 12.1%; p = 0.03). A non-significantly increased incidence of
      serositis was also observed in late-onset SLE patients (33.9% versus 22.0%; p =
      0.13). Hypocomplementaemia (72.9% versus 91.2%) and positive results for anti-DNA
      and anti-Sm (49.2% and 6.8% versus 68.1% and 23.1, respectively) were
      significantly less common in late-onset SLE patients than in early-onset SLE. The
      probability of survival was reduced in late-onset SLE (p < 0.001). With respect
      to this, the 10-year and 15-year survival probability were 74.9 % and 63.3% in
      the late-onset SLE group and 96.3% and 91.0% in patients with early-onset SLE,
      respectively. In conclusion, our results confirm that in NW Spain SLE is not
      uncommon in individuals 50 years and older. In keeping with earlier studies, late
      onset SLE patients from NW Spain have some clinical and laboratory differences
      with respect to those individuals with early-onset SLE. Our data support the
      claim of a reduced probability of survival in the older age-group of SLE
      patients.

PMID- 22652633
TI  - Abstracts of the 17th Meeting of the European Society of Neurosonology and
      Cerebral Hemodynamics. Venice, Italy. May 17-20, 2012.

PMID- 22652634
TI  - Long-term efficacy of pulmonary rehabilitation in patients with occupational
      respiratory diseases.
AB  - BACKGROUND: Pulmonary rehabilitation is a well-recognized treatment option in
      chronic obstructive lung disease improving exercise performance, respiratory
      symptoms and quality of life. In occupational respiratory diseases, which can be
      rather cost-intensive due to the compensation needs, very little information is
      available. OBJECTIVES: This study aims at the evaluation of the usefulness of
      pulmonary rehabilitation in patients with occupational respiratory diseases,
      partly involving complex alterations of lung function and of the sustainability
      of effects. METHODS: We studied 263 patients with occupational respiratory
      diseases (asthma, silicosis, asbestosis, chronic obstructive pulmonary disease)
      using a 4-week inpatient rehabilitation program and follow-up examinations 3 and
      12 months later. The outcomes evaluated were lung function, 6-min walking
      distance (6MWD), maximum exercise capacity (Wmax), skeletal muscle strength,
      respiratory symptoms, exacerbations and associated medical consultations, quality
      of life (SF-36, SGRQ), anxiety/depression (HADS) and Medical Research Council and
      Baseline and Transition Dyspnea Index scores. RESULTS: Compared to baseline,
      there were significant (p < 0.05) improvements in 6MWD, Wmax and muscle strength
      immediately after rehabilitation, and these were maintained over 12 months (p <
      0.05). Effects were less pronounced in asbestosis. Overall, a significant
      reduction in the rate of exacerbations by 35%, antibiotic therapy by 27% and use
      of health care services by 17% occurred within 12 months after rehabilitation. No
      changes were seen in the questionnaire outcomes. CONCLUSIONS: Pulmonary
      rehabilitation is effective even in the complex settings of occupational
      respiratory diseases, providing sustained improvement of functional capacity and
      reducing health care utilization.

PMID- 22652635
TI  - A multicomponent synthetic strategy for two-carbon-tethered 1,3-oxathiole-indole
      pairs.
AB  - An efficient methodology for the multicomponent synthesis of new and highly
      functionalized heterocycles containing 1,3-oxathiole and indole units which are
      connected through an sp(2)-C(2) bridge has been developed. This domino reaction
      enables successful assembly of three new sigma bonds including a C-S bond and a C
      O bond in a one-pot operation. Features of this strategy include mild conditions,
      convenient one-pot operation, and high stereo- and regioselectivity.

PMID- 22652636
TI  - Random/aligned electrospun PCL/PCL-collagen nanofibrous membranes: comparison of
      neural differentiation of rat AdMSCs and BMSCs.
AB  - In this study, the aligned (A) and randomly oriented (R) polycaprolactone (PCL-A
      and PCL-R) and PCL/collagen (PCL/Col-A and PCL/Col-R) nanofibers were electrospun
      onto smooth PCL membranes (PCLMs) prepared by solvent casting. In order to
      investigate the effects of chemical composition and nanotopography of fibrous
      surfaces on proliferation and on neural differentiation of mesenchymal stem cells
      (MSCs), adipose and bone marrow-derived rat MSCs (AdMSCs and BMSCs) were
      cultivated in suitable media i.e. inducing medium containing basic fibroblast
      growth factor (bFGF) and epidermal growth factor (EGF), and cell maintenance
      medium (CMM). BMSCs adhered and proliferated on all nanofibrous membranes more
      efficiently than AdMSCs. PCL/Col-A was found as the most convenient surface
      supporting proliferation in both cell types. Immunofluorescence staining
      indicated that BMSCs and AdMSCs are prone for differentiation to oligodendrocytes
      more than they differentiate to other neuronal cell types. PCL-A nanofibrous
      membranes supported differentiation of MSCs to O4(+) (an oligodendrocytes surface
      antigen) cells in both culture media. The intensity of immunoreactivity of O4(+)
      cells differentiated from BMSCs on PCL-A was highest when compared with the other
      groups (p < 0.001). Some BIII-T signed neural cells were investigated on PCL-A
      nanofibrous membranes, but the intensity of immunoreactivity was lower than that
      of O4(+) cells. In conclusion, this study can be evaluated to establish the cell
      therapy strategies in neurodegenerative disorders, which are relevant to
      oligodendrocyte abstinence using BMSCs or AdMSCs on aligned nanofibrous
      membranes.

PMID- 22652640
TI  - A review of factors affecting antler composition and mechanics.
AB  - Antlers constitute the only mammal model for limb regeneration. A number of
      factors affect antler regeneration. In this review, we examine such factors and
      the potential consequences for organ regeneration. As body mineral stores are
      depleted to grow antlers, physiological exhaustion is shown in the mineral
      composition, mechanical performance and, according to preliminary studies,
      porosity of the antler bone material. Nutrition plays an important role in antler
      characteristics. Thus, antler composition can be used as a diagnostic tool to
      assess mineral deficiencies in deer. Studies on ecological effects of exceptional
      weather in plants suggest that minor minerals, particularly Mn, may play
      disproportionately roles in mechanical performance of bone material. This
      suggests that Mn (and perhaps other minerals) is essential to incorporate Ca and
      P from resorbed skeleton material in antlers. Apart from implications for game
      management, some effects may have applications for medicine.

PMID- 22652641
TI  - Vaginal DNA vaccination against infectious diseases transmitted through the
      vagina.
AB  - There is an urgent need for the development of vaccines against genital virus
      infections that are transmitted through heterosexual intercourse, including the
      HIV and HPV. In general, the surface of female genital mucosa, including vaginal
      mucosa, is the most common site of initiation of these infections. Thus, it is
      becoming clear that successful vaccines must induce both cellular and humoral
      immune responses in both the local genital tract and systemically. We believe
      that a strong vaginal immune response could be obtained by inducing strong gene
      expression of antigen-coding DNA in the local targeted tissue. In order to
      improve transfection efficiency in the vagina, it is important that methods
      allowing breakthrough of the various barriers, such as the epithelial layer,
      cellular and nuclear membrane, are developed. Therefore, systems providing less
      invasive and more effective delivery into the subepithelial layer are required.
      In this review, we will introduce our studies into efficient vaginal DNA
      vaccination methods, focusing on the effects of the menstrual cycle, utilization
      of the combination of functional peptides, and use of a needle-free injector.

PMID- 22652639
TI  - High sensitive troponin T in individuals with chest pain of presumed ischemic
      origin.
AB  - This study was aimed at assessing the bias of high sensitive cardiac troponin T
      vs. the standard cardiac troponin T in a selected population with chest pain of
      presumed cardiac origin. Serum cTnT was determined in 132 patients and in 106
      apparently healthy controls by both assays. The hs-cTnT outperformed the standard
      generation assay by: i) allowing a larger and earlier diagnosis of AMI (74.2
      percent vs. 64.3 percent patients resulted positive at the final diagnosis of AMI
      when tested with the hs-cTnT or the std-cTnT assay, respectively); ii) showing a
      better time-dependent dynamics in patients with AMI due to a higher precision at
      low concentrations; iii) identifying, within the controls, 6 subjects in whom a
      further examination revealed the presence of chronic asymptomatic cardiac
      ischemia. The results underscore the excellent performance of the hs-cTnT assay
      in our population. The use of this test can thus be strongly recommended in
      subjects presenting to the emergency unit with chest pain of presumed ischemic
      origin in order to increase the probability of earlier diagnosis of AMI,
      especially in non-STEMI.

PMID- 22652642
TI  - The immune system: endogenous anticancer mechanism.
AB  - The genetic alterations acquired by cancer cells are identified by diverse immune
      mechanisms, creating a complex network of interactions that can either favor or
      control tumor growth. Defects and impairments in the immune system are associated
      with cancer development. Compelling new evidences are also available regarding
      the protective value of anti-tumor adaptive immune responses, both local and
      systemic, developed by the host. More recently, the identification of new subsets
      of T helper, T cytotoxic, and dendritic cells, unraveled new forms of
      interactions between immune and tumor cells. The immune system is a powerful ally
      in the control of cancer development, metastasis and recurrence, due to two
      important properties that are absent in most anti-cancer treatments--specificity,
      and long-lasting memory. These properties are being increasingly explored in
      cancer therapy, from the wide use of monoclonal antibodies to the still
      experimental dendritic cell based therapies. Now, more than ever, the
      preservation as well as the recruitment of immune responses in the host
      constitute important approaches to be applied in cancer therapy.

PMID- 22652644
TI  - Autoimmunity and lung transplantation.
AB  - Lung transplantation is a viable treatment option for a variety of end-stage lung
      diseases. Since the first successful human lung transplant about 20 years ago,
      tremendous progress has been made in this field. However, lung allografts have
      the poorest long term survival compared to other solid organs. The predominant
      reason for this is the development of chronic rejection, also known as
      bronchiolitis obliterans syndrome (BOS). Although the traditional view supports
      alloimmunity as the major cause of chronic rejection, emerging evidence reveals a
      complex interplay of multiple etiologies including peri-operative stressors,
      inflammation, and autoimmunity along with alloimmunity. Identification of
      autoimmunity in the pathogenesis of BOS is an exciting recent finding in lung
      transplantation and promises to introduce novel strategies for future therapeutic
      interventions. In this review, we discuss recent studies and concepts related to
      the role of autoimmunity in the development of BOS.

PMID- 22652643
TI  - GST P1, a novel downstream regulator of LRRK2, G2019S-induced neuronal cell
      death.
AB  - The enhanced neurotoxicity of the Parkinson's disease-associated LRRK2 mutant,
      G2019S, than its wild-type counter-part has recently been reported.
      Overexpression of LRRK2 (G2019S) in cultured neural cells results in caspase-3
      dependent apoptosis via a yet undefined signaling pathway. Elucidation of the
      mechanism underlying LRRK2 (G2019S) neurotoxicity may offer new insights into the
      pathogenesis of Parkinson's disease. In this study, we identified glutathione s
      transferase P1 (GSTP1) as a selective target whose expression is negatively
      regulated at the transcriptional levels via promoter hyper-methylation by LRRK2
      (G2019S). Overexpression of LRRK2 (G2019S) in the human neuronal cell line SH
      SY5Y markedly suppressed the expression of GSTP1 prior to any manifestation of
      cell death. Moreover, shRNA-mediated knockdown of endogenous GSTP1 expression
      exacerbated LRRK2 (G2019S) neurotoxicity, whereas overexpression of GSTP1
      protected against LRRK2 (G2019S)-induced caspase-3 activation and neuronal
      apoptosis. In conclusion, the results suggest a previously undefined signaling
      mechanism underlying the neurotoxic effect of LRRK2 (G2019S), in which LRRK2
      (G2019S) triggers oxidative stress in cells and, in turn, results in caspase
      dependent apoptosis at least in part by suppressing the expression of GSTP1.

PMID- 22652645
TI  - Adenovirus KH901 promotes 5-FU antitumor efficacy and S phase in LoVo cells.
AB  - A combination of oncolytic and chemotherapeutic agents has been used to kill
      cancer cells. However, the effect of oncolytic adenoviruses on the cell cycle
      remains to be determined. Cytotoxicity assays were performed to determine cell
      death in cells treated with 5-fluorouracil (5-FU) alone or in combination with
      the oncolytic adenovirus KH901. Dynamic changes in the cell cycle, cell
      proliferation, and apoptosis-related proteins including p-AKT, Bcl-2, Bax, and
      caspase 3 were investigated after treatment with 5-FU with or without KH901. A
      higher proportion of S-phase cells were observed after treatment with KH901 and 5
      FU than with 5-FU alone. p-AKT, Bcl-2, and Bax expression was increased upon
      treatment with KH901, whereas the expression of caspase-3 was not induced upon
      treatment with KH901 with or without 5-FU. KH901 exhibited significant potential
      as an oncolytic adenovirus and increased cell death in combination with 5-FU in
      LoVo cells, as compared to 5-FU alone. In conclusion, KH901 stimulates LoVo cells
      to enter the S-phase by activation of p-AKT, which could partly explain its
      synergistic effect with 5-FU on LoVo cell cytotoxicity.

PMID- 22652646
TI  - Hemodialysis access monitoring and surveillance, how and why?
AB  - Hemodialysis access is the 'life line' for patients on renal replacement therapy.
      Vascular access failure and complications are the second leading cause for
      hospitalization of patients on hemodialysis. The concept of access monitoring is
      based on the basic tenet that identification of patients at risk of developing
      future access failure, coupled with elective intervention will decrease the
      incidence of hemodialysis access failure and improve patient outcomes. Clinical
      monitoring and surveillance techniques are very effective in detecting
      hemodialysis access lesions. However, the studies analyzing the impact of
      monitoring and surveillance have yielded a variety of controversial results,
      which is likely the result of the differences in methodology and use of a variety
      of parameters. Despite the controversy surrounding the value of monitoring and
      surveillance, the Conditions of Coverage for dialysis providers mandate
      monitoring with appropriate and timely referrals to achieve and sustain vascular
      access. This review discusses pros and cons of various monitoring and
      surveillance techniques and suggests a strategy based on current literature.

PMID- 22652648
TI  - C-reactive protein and obstructive sleep apnea syndrome in children.
AB  - Obesity has emerged as one of the most important epidemics in the western
      hemisphere, and as its prevalence continues to increase in children, the
      associated risk for cardiovascular and metabolic complications follows parallel
      increases in prevalence, and reflects activation of underlying inflammatory
      pathways. The obstructive sleep apnea syndrome (OSAS) is a frequent condition in
      children associated with intermittent upper airway obstruction during sleep, its
      prevalence is markedly increased in the presence of obesity, and is associated
      with activation of similar inflammatory mechanisms as those activated by obesity,
      suggesting that the 2 disorders may reciprocally contribute to their adverse
      consequences.  C-reactive protein (CRP) is a prototypic marker of inflammation
      that has repeatedly shown promise as a potentially reliable biomarker of
      cardiovascular morbidity. In addition, under certain circumstances CRP may
      enhance inflammation, oxidative stress, and pro-coagulant activity and thus
      promote atherogenesis.  In this paper, we will critically review the available
      evidence linking OSAS to systemic inflammation in children using CRP levels as
      the reporter biomarker.

PMID- 22652647
TI  - Cigarette smoke enhances chemotaxis via acetylation of proline-glycine-proline.
AB  - Several chronic lung diseases have been linked to cigarette smoking (Chronic
      Obstructive Pulmonary Disease (COPD), and cancer are associated with increased
      tobacco use).  We recently described a collagen fragment, proline-glycine-proline
      (PGP), chemotactic for neutrophils, that appears to play a role in COPD, cystic
      fibrosis, and bronchiolitis obliterans syndrome.  PGP can exist in either its
      native or acetylated form (NAcPGP), although the mechanism of N-terminal
      acetylation remains unknown.  This work investigates the possibility that
      cigarette smoke (CS) and its components acetylate PGP, describing a possible
      mechanism for some of the chronic inflammation seen in tobacco-associated
      disease. CSE and CSC (3.56 and 12.38 ng/ml NAcPGP respectively, p less than 0.01)
      and its components (acrolein, acetaldehyde, and methyl glyoxal) acetylated PGP
      (0.51, 1.03, and 0.23 ng/ml NAcPGP, p less than 0.01).  Both N-acetyl-cysteine
      and carbocysteine (scavengers of reactive aldehydes) blocked chemical acetylation
      of PGP by CS (100 percent  and 97 percent  inhibition, respectively, p less than
      0.01).  NAcPGP is more chemoattractive to neutrophils, and less susceptible to
      degradation by Leukotriene-A4-Hydrolase (detected in the lung).  These
      experiments propose a mechanism for the increased neutrophil recruitment seen in
      smoking-associated lung diseases.

PMID- 22652649
TI  - Early atherosclerotic plaques show evidence of infection by Chlamydia pneumoniae.
AB  - Chlamydia pneumoniae (Cpn) could play an important role in the development of
      atherosclerosis. Cpn interferes with HIF-1alpha regulation in infected host cells
      during intracellular replication in hypoxia. We obtained carotid artery specimens
      with low (n=38), high (n=25) levels of stenosis and 10 middle cerebral arteries.
      Fifty eight percent of the carotids with low levels of stenosis showed evidence
      of the viable organism. Ninety one percent of the positive results were derived
      from pre-atheromatous lesions. Only 12 percent of plaques removed at
      endarterectomy showed the presence of Cpn DNA. All middle cerebral arteries
      failed to show evidence of live Chlamydia. Ninety one percent of sera from 22
      endarterectomy patients failed to show the presence of Cpn antibodies.
      Immunohistology of carotid arteries with low levels of stenosis was used to
      confirm the presence of HIF-1alpha in infected specimens and showed a correlation
      between the over-expression of HIF-1alpha and Cpn in the plaque (p less than
      0.05). Cpn might play an important role in activation and development of the
      initial stages of atherosclerotic lesions.

PMID- 22652650
TI  - Defining the pathogenesis of inflammatory and immune diseases through database
      mining.
AB  - Recent research in human and animal genomes, transcriptomes, proteomes, and
      antigen-omes has generated a large library of data and has led to the
      establishment of many experimental data-based searchable databases. Scientists
      now face new, unprecedented challenges to develop more systemic methods to
      analyze experimental data and generate new hypotheses. This review will briefly
      summarize our pioneering efforts in using new database mining methods to answer
      important questions in inflammatory and immune-related diseases. The new
      principles and basic methodologies of database mining developed in Dr. Yang's
      laboratory will be delineated in the following studies: 1) a stimulation
      responsive alternative splicing model for generating untolerized autoantigen
      epitopes; 2) a three-tier model for caspase-1 activation and inflammation
      privileges of various organs; and 3) a group of anti-inflammatory microRNAs which
      inhibit proatherogenic gene expression during atherogenesis. With technological
      advances, database mining has provided important insight into new directions for
      experimental research.

PMID- 22652651
TI  - The role of micronutrients in the diet of HIV-1-infected individuals.
AB  - Vitamins, zinc and selenium are important micronutrients that play crucial
      functions at the cellular and molecular level. Immune response of several
      different cell types can be modulated by these micronutrients. Deficiency in
      micronutrients has been extensively reported in HIV-1-infected individuals and
      further correlated with CD4+ T-cell count, HIV-1 plasma viral load, disease
      progression and mortality. Supplementation by micronutrients has had
      controversial effects. Thorough future investigations and trials are certainly
      needed to strategically plan evidence-based interventions. Here, we review the
      available data on use of micronutrients during the course of HIV-1 infection.

PMID- 22652652
TI  - Role of p14(ARF) alterations in endometrial tumorigenesis: a mini-review.
AB  - In the current mini-review, we present a short overview of genetic as well as
      immunohistochemical p14(ARF) alterations either in primary human endometrial
      carcinomas (ECs) or in metastatic lesions originated from malignant endometrium.
      The prognostic utility of p14(ARF) in uterine malignancies has also been briefly
      discussed.

PMID- 22652653
TI  - A bivariate variance components model for mapping iQTLs underlying endosperm
      traits.
AB  - Genomic imprinting plays a pivotal role in early stage development in plants.
      Linkage analysis has been proven to be useful in mapping imprinted quantitative
      trait loci (iQTLs) underlying imprinting phenotypic traits in natural populations
      or experimental crosses. For correlated traits, studies have shown that
      multivariate genetic linkage analysis can improve QTL mapping power and
      precision, especially when a QTL has a pleiotropic effect on several traits. In
      addition, the joint analysis of multiple traits can test a number of biologically
      interesting hypotheses, such as pleiotropic effects vs close linkage. Motivated
      by a triploid maize endosperm dataset, we extended the variance components
      linkage analysis model incorporating imprinting effect  proposed by Li and Cui
      (2010) to a bivariate trait modeling framework, aimed to improve the mapping
      precision and to identify pleiotropic imprinting effects. We proposed to
      partition the genetic variance of a QTL into sex-specific allelic variance
      components, to model and test the imprinting effect of an iQTL on two traits.
      Both simulation studies and real data analysis show the power and utility of the
      method.

PMID- 22652655
TI  - Sleep, inflammation and cardiovascular disease.
AB  - In data from prospective cohort studies, self report of insufficient or disturbed
      sleep is related to increased overall and cardiovascular morbidity. Inflammation
      is established as a key mechanism in the development of arteriosclerotic heart
      and vascular disease. Inflammation has been considered a possible link between
      short sleep and cardiovascular disease and morbidity. Measures of inflammation
      are increased by experimental sleep deprivation, but in cohort studies a
      relationship of sleep duration to inflammatory markers is less clear. In these
      studies the association of self reported short sleep to cardiac morbidity is
      confounded by many psychological and socioeconomic variables. More studies are
      needed to explain the link between short sleep duration and cardiac morbidity.
      Experimental studies of sleep deprivation mimicking habitual shortened sleep over
      long time intervals, and studies employing sleep extension in habitual short
      sleepers will allow better characterization of the health benefits of adequate
      sleep duration. Prospective cohort studies should include objective measures of
      sleep duration and should to control for the known confounding variables.

PMID- 22652654
TI  - Very early-initiated physical rehabilitation protects against ischemic brain
      injury.
AB  - Recent clinical data suggest that very early initiated physical rehabilitation
      (VEIPR) within 24 hours after stroke may reduce morbidity.  However, there is
      limited evidence to support the beneficial effects of VEIPR and the underlying
      mechanisms are yet unknown. The present study investigated the effect of VEIPR on
      brain damage, inflammation, and neurobehavioral outcomes following cerebral
      ischemia. Rats that underwent transient focal cerebral ischemia (tFCI) were
      randomly assigned to VEIPR or non-exercise (NE) groups. VEIPR was induced 24
      hours after the insult by initiating treadmill training for a maximum of 14 days
      while the NE group remained sedentary in their cages during this period. The
      results indicated that VEIPR significantly improved recovery of functional
      behavior as measured by neurological score, foot fault test, and Morris water
      maze performance. We also demonstrated that VEIPR significantly reduced infarct
      volume, brain water content, BBB damage, and acute inflammatory response. In
      summary, our results provide novel evidence that VEIPR confers marked
      neuroprotection against experimental stroke by attenuating pro-inflammatory
      reactions, brain edema, BBB damage, and cognitive and behavioral deficits.

PMID- 22652656
TI  - Cancer stem cells and niche mircoenvironments.
AB  - The isolation and characterization of cancer stem cells as the cells that
      initiate cancer has lead to a paradigm shift in our approaches toward cancer
      management. According to this new concept, only a small percentage of cells,
      termed cancer stem cells (CSCs), drive tumor formation and progression and give
      rise to the heterogeneity of tumor cells. It has been a decade since the cancer
      cell was proclaimed to be, self-sufficient in growth signals. However, recent
      researches suggest that even the CSCs rely heavily on the ancillary cells present
      in the tumor stroma for their persistence in the quiescent state. In this review
      we will discuss a complex integrated ongoing process in the tumor
      microenvironment which enables the CSCs to maintain their undifferentiated yet
      plastic state.

PMID- 22652657
TI  - Obesity and breast cancer: mechanisms and therapeutic implications.
AB  - Obesity is a known risk factor for postmenopausal breast cancer, whereby factors
      produced by the adipose tissue are known to directly and indirectly affect tumour
      growth. It is now becoming increasingly clear that both obesity and cancer arise
      as a consequence of dysregulated metabolism, both in response to altered energy
      status and endocrine factors, and to intrinsic changes within cells. Moreover,
      both obesity and cancer lead to localised inflammation, whereby inflammatory
      cytokines and prostaglandins are produced by adipose tissue and tumour cells.
      Obesity is also a risk factor for type 2 diabetes, with a consequential increase
      in circulating insulin and insulin-like growth factor-I (IGF-I) known to promote
      tumour cell growth. Interestingly, these factors converge to increase aromatase
      expression within the breast and hence, estrogen production, thereby increasing
      the risk of breast cancer and the growth of breast tumour cells. Therapies aimed
      at treating obesity/diabetes are therefore attractive options for the treatment
      of postmenopausal breast cancer.

PMID- 22652658
TI  - Homocysteine-impaired angiogenesis is associated with VEGF/VEGFR inhibition.
AB  - This study investigated the effects of homocysteine (Hcy) on angiogenesis in
      cultured human umbilical vein endothelial cells (HUVEC) and zebrafish embryos. We
      found that Hcy (50 micromol/L) significantly decreased cell numbers, viability,
      and induced a G1/S arrest in HUVEC in the presence of adenosine (Ade, 50
      micromol/L). Hcy, in combination with Ade, reduced migration and suppressed tube
      like formation on Matrigel in HUVEC. Further, Hcy reduced subintestinal vessel
      formation in zebrafish embryos. Interestingly, Hcy-induced inhibitory effects on
      cell growth, migration, tube-like formation, and vessel formation in HUVEC and
      zebra fish embryos were abolished by the supplement of recombinant VEGF (10
      ng/ml). Finally, Hcy in combination with Ade reduced the mRNA levels of VEGF,
      VEGFR-1, VEGFR-2, and attenuated protein levels of VEGF, ERK1/2 and Akt. The
      present study suggests that Hcy inhibits angiogenesis, and that the mechanism
      anti-angiogenic effects of Hcy may be through VEGF/VEGFR, Akt, and ERK1/2
      inhibition.

PMID- 22652659
TI  - Igf1r is not required for AIB1-induced mammary hyperplasia and ductal branching.
AB  - The oncogene AIB1 (amplified in breast cancer 1) is a transcriptional coactivator
      which is up-regulated in many types of tumors including breast cancer. Studies
      with cell lines and animal models reveal that AIB1 interacts with the IGF-I
      signaling pathway at different molecular levels. To determine whether AIB1
      dependent cell growth requires IGF-I signaling, we deleted the Igf1r gene
      specifically in the mammary gland of transgenic mice which overexpress AIB1 and
      are characterized by the development of epithelial hyperplasia, a pre-neoplastic
      change in breast tissue. Loss of Igf1r alone reduced cell proliferation, ductal
      branching and fat pad occupancy in comparison with wild-type glands. However, in
      the transgenic mice that overexpress moderate levels of AIB1, the absence of
      Igf1r had a minimal effect on epithelial hyperplasia and ductal branching in the
      mammary gland. Thus, our results confirm the essential role of Igf1r in mammary
      gland morphogenesis and demonstrate that overexpression of AIB1 circumvents the
      requirement for the Igf1r pathway in promoting epithelial growth during mammary
      development.

PMID- 22652660
TI  - Gene therapy in age related macular degeneration and hereditary macular
      disorders.
AB  - In ophthalmology, administration of the therapeutic agent can be difficult due to
      the tight barriers in the eye. Multiple injections may be needed to allow the
      therapeutic agent to reach adequate levels in retina and choroidea which may
      increase the risk of complications including endophthalmitis, cataract and
      haemorrhages. Optimal methods for the delivery of therapeutic agents to the
      posterior segments of the eye have not yet been developed. Gene therapy offers an
      alternative where the therapeutic protein or proteins can be induced in the
      target tissue for a prolonged period of time after a single injection. The eye is
      a promising target for gene therapy due to its small size and tissue boundaries
      preventing leakage of the therapeutic material to other tissues or systemic
      circulation. However, most of the work in ocular gene therapy is still at the
      preclinical phase; only three vectors have reached phase 1/2 clinical trials.
      This review summarizes basic principles and current status of gene therapy in age
      related macular degeneration and hereditary macular disorders.

PMID- 22652661
TI  - Assessing the clinical significance of tumor markers in common neoplasms.
AB  - The term tumor markers include a spectrum of molecules and substances with widely
      divergent characteristics whose presence in the significant amount can be related
      to the malignant disease. An ideal tumor marker should have high specificity and
      sensitivity, which would allow its use in early diagnosis and prognosis of
      malignant disease, as well as in prediction of therapeutic response and follow-up
      of the patients. Numerous biochemical entities have emerged as potentially
      valuable tumor markers so far, but only few markers showed to be of considerable
      clinical reliability and have been accepted into standard clinical practice.
      Recent development of genomics and proteomics has enabled the examination of many
      new potential tumor markers. Scientific studies on discovery, development, and
      application of tumor markers have been proceeding quite rapidly providing great
      opportunities for improving the management of cancer patients. This review is
      focusing on the clinical usefulness of various tumor markers already in clinical
      practice as well as certain potential markers, giving a brief description of
      their prognostic and predictive significance in most common malignancies.

PMID- 22652662
TI  - Expression, identification and purification of human FMRP isoform 10.
AB  - Fragile X syndrome (FXS), which is the most frequently inherited mental
      retardation after Down syndrome, is caused by the absence of the fragile X mental
      retardation protein (FMRP) encoded by the fragile X mental retardation 1 (FMR1)
      gene. Patients with FXS can be identified by antibody tests that detect the
      absence of FMRP caused by loss-of-function mutations including the prevalent CGG
      repeat amplification in lymphocytes. Although the expression of recombinant FMRP
      in prokaryotic and eukaryotic expression systems has been achieved in different
      laboratories, the solubilization and purification of this protein is time
      consuming, varies with each protocol, and often results in low yield. In this
      study, glutathione S-transferase FMRP fusion protein (GST-FMRP) was expressed in
      and purified from Escherichia coli BL21(DE3) pLysS cells transformed with pGEX-6P
      1 fusion expression vector containing the FMR1 cDNA. The recombinant GST-FMRP was
      purified on a glutathione sepharose 4B affinity column and detected using SDS
      PAGE followed by western blotting with anti-FMRP antibody. This highly purified
      and soluble GST-FMRP protein can be very beneficial for generating anti-FMRP
      antibodies and developing FXS diagnosis kits.

PMID- 22652663
TI  - Molecular mediators of polymicrobial sepsis.
AB  - Sepsis is still a major cause of postoperative morbidity and mortality. Numerous
      biochemical indicators have been evaluated regarding their potential in
      predicting prognosis in sepsis. Generally, one must differentiate between
      indicators: those for preoperative risk of lethal sepsis, those for early
      prediction of lethal outcome and those for evaluating effectiveness of therapy.
      In the past, immunomodulatory therapies developed in various animal studies
      failed to be successful in humans. It has been proposed that present models have
      to be reevaluated, and new, clinically more relevant models should be evolved.
      This article will give a short overview on the most common animal models and a
      comprehensive overview on markers for sepsis in animal models and clinical
      studies. The focus will be on abdominal sepsis with a mortality rate up to 80
      percent after major surgery. Two animal models designed to closely mimic the
      clinical course of intra-abdominal sepsis, will be compared. Furthermore,
      relevant clinical parameters for predicting prognosis before and after major
      visceral surgery are illustrated.

PMID- 22652664
TI  - Identifying lipid metabolism genes in pig liver after clenbuterol administration.
AB  - Clenbuterol is a repartition agent (beta 2-adrenoceptor agonist) that can
      decrease fat deposition and increase skeletal muscle growth at manageable dose.
      To better understand the molecular mechanism of Clenbuterol's action, GeneChips
      and real-time PCR were used to compare the gene expression profiles of liver
      tissue in pigs with/without administration of Clenbuterol. Metabolism effects and
      the global gene expression profiles of liver tissue from Clenbuterol-treated and
      untreated pigs were conducted. Function enrichment tests showed that the
      differentially expressed genes are enriched in glycoprotein protein, plasma
      membrane, fatty acid and amino acid metabolic process, and cell differentiation
      and signal transduction groups. Pathway mining analysis revealed that
      physiological pathways such as MAPK, cell adhesion molecules, and the insulin
      signaling pathway, were remarkably regulated when Clenbuterol was administered.
      Gene prioritization algorithm was used to associate a number of important
      differentially expressed genes with lipid metabolism in response to Clenbuterol.
      Genes identified as differentially expressed in this study will be candidates for
      further investigation of the molecular mechanisms involved in Clenbuterol's
      effects on adipose and skeletal muscle tissue.

PMID- 22652666
TI  - Role of Toll like receptors in the antibody response to encapsulated bacteria.
AB  - Encapsulated bacteria are major pathogens in humans. The capsular polysaccharides
      (PS) of these bacteria are T-independent type 2 antigens, are not processed by
      antigen presenting cells and do not induce T cell help. PS antigens are poor
      immunogens in children less than two years, the peak age incidence of
      encapsulated bacterial infection. The TNF family receptors BAFFR and TACI
      interaction with the cytokines BAFF and APRIL are essential co-stimulatory
      factors for humoral responses to PS. Linkage of PS to a carrier protein to make
      glycoconjugate vaccines, enhances the immune response to PS similar to a T cell
      dependent antigen. Multiple doses of glycoconjugate vaccines are required to
      elicit protection, making their use in the developing world problematic. TLR
      engagement augments BAFF mediated PS antibody responses and TLR ligands serve as
      adjuvants for induction of anti-PS antibodies either for pure PS or for PS
      protein conjugate vaccines. A variety of TLR ligands stimulate increased
      production of antibodies directed to both PS and protein components of
      encapsulated bacteria, and glycoconjugate vaccines, suggesting their future role
      in immunization strategies.

PMID- 22652667
TI  - Use of BMPs and bisphosphonates in improving bone fracture healing.
AB  - In orthopaedics, focus is often placed on increasing bone formation by an
      anabolic drug like the recombinant human bone morphogenetic protein (rhBMP).
      However, premature or excessive bone resorption, due to stress-shielding,
      instability or infection/inflammation can lead to poor, delayed, or absent bone
      union. Anti-catabolic drugs such as bisphosphonates have therefore been explored
      to improve bone repair. This short review discusses the current literature
      underlying the anabolic-catabolic paradigm for bone repair with a focus on BMP
      and bisphosphonate combination approaches.

PMID- 22652668
TI  - Imidazolineoxyl N-oxide induces COX-2 in endothelial cells:  role of free
      radicals.
AB  - cPTIO (2-[4-carboxyphenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) exerts
      beneficial actions on systemic inflammatory response. Besides its nitric oxide
      (NO) scavenging properties cPTIO could exert beneficial effects through
      modulation of arachidonic acid metabolism. We studied the effect of cPTIO on the
      biosynthesis of vasoactive prostaglandins (PG) by endothelial cells. Human cord
      umbilical vein endothelial cells (HUVEC) were treated with cPTIO, and expression
      of cycloxygenase (COX) isoenzymes in terms of mRNA and protein was determined by
      real-time-PCR and immunoblotting. Release of PGE2 (as index of untransformed PGH2
      release) and 6-oxo-PGF1alpha (PGI2 stable metabolite) was determined by enzyme
      immunoassay. cPTIO significantly increases the release of untransformed PGH2
      associated to the induction of COX-2 expression. Experiments with NO-synthase
      inhibitors and radical scavengers showed that induction of COX-2 by cPTIO was
      mediated by free radical species, likely caused by the mobilization of NO from
      cellular stores. Finally, using specific signal-transduction inhibitors we show
      the involvement of Src/PI3-K/PKC pathway. Additional effects other than a direct
      NO scavenging activity may confer therapeutic advantages to cPTIO as compared
      with NO-synthase inhibitors for the treatment of systemic inflammation-associated
      vascular hyporeactivity.

PMID- 22652665
TI  - Age related cardiovascular dysfunction and effects of physical activity.
AB  - The aim of the present article is to review  the principal  pathogenetic pathways
      of age-related cardiovascular  changes and the  positive effects of physical
      activity on these changes  as well as on  related cardiovascular dysfunction. The
      ageing mechanisms reviewed have been grouped into reduced tolerance  of oxidative
      stress, loss of cardiac stem cells, cardiovascular remodeling and impairment of
      neurovegetative control. New  pathogenetic conditions and their tests are
      described (sirtuines, telomere length, heart rate variability). Age related
      cardiovascular changes predispose the individual to arterial hypertension, heart
      failure and arrythmia. A broad spectrum of tests are available to indentify and
      monitor the emerging cardiovascular dysfunction. Physical activity influences all
      age related cardiovascular mechanisms, improves cardiovascular function and even,
      at moderate intensity can reduce mortality and heart attack risk. It is likely
      that the translation of laboratory studies to humans will improve understanding 
      and stimulate the use of physical activity to benefit cardiovascular patients.

PMID- 22652669
TI  - MicroRNA-27a activity is not suppressed in porcine oocytes.
AB  - MicroRNAs (miRNAs) are a class of small noncoding RNAs involved in multiple
      cellular processes. Recent findings indicate that miRNA activity is globally
      suppressed in mouse oocytes. However, whether miRNAs are expressed and function
      in porcine oocytes remains unknown. In this study, our aims were to ascertain if
      miRNA biogenesis occurs and whether miRNA activity is globally suppressed during
      porcine oocyte maturation. First, to identify if miRNA biogenesis occurred, a
      TaqMan low-density array containing 365 mature human miRNAs was used to examine
      miRNA expression. This analysis revealed dynamic changes in miRNA expression,
      suggesting miRNA biogenesis during porcine oocyte maturation. Then, to identify
      if miRNA activity was globally suppressed in porcine oocytes, we focused on miR
      27a, which functions in the cell cycle. miR-27a was found to facilitate the first
      cleavage and repress the translation of its messenger RNA target (MAP2K4),
      suggesting that miR-27a activity was not suppressed in porcine oocytes. Taken
      together, our results suggest that miRNA activity was not globally suppressed in
      porcine oocytes, at least for miR-27a. However, because we only investigated the
      activity of miR-27a, further experiments are definitely required to ascertain
      this point.

PMID- 22652670
TI  - Role of obesity , alcohol and smoking on bone health.
AB  - The burden of osteoporosis is increasing in all societies. In comparison with
      other organs or apparatuses fewer studies have focused on incorrect lifestyles
      and bone. This article reviews clinical and experimental studies on the effects
      of obesity, alcohol abuse and smoking on bone. Overweight and obesity protect
      bone, thus reducing the fracture risk and the development of osteoporosis in
      older adults. However, extreme obesity (body mass index more than 40
      kilogram/meter squared) seems to be a risk factor for osteoporosis. Moderate
      alcohol consumption may have a protective effect, whereas excessive consumption
      is an important risk factor. Cytokines are the main mediators of the detrimental
      effects of obesity and alcohol. Smoking contributes to bone loss and fracture
      probably by interfering with estrogens, calcium and vitamin D. Health information
      campaigns against these harmful lifestyles should be strengthened by using
      available scientific information to increase awareness about their consequences
      on the bone.

PMID- 22652671
TI  - A U-Statistic-based random Forest approach for genetic association study.
AB  - Variations in complex traits are influenced by multiple genetic variants,
      environmental risk factors, and their interactions. Though substantial progress
      has been made in identifying single genetic variants associated with complex
      traits, detecting the gene-gene and gene-environment interactions remains a great
      challenge. When a large number of genetic variants and environmental risk factors
      are involved, searching for interactions is limited to pair-wise interactions due
      to the exponentially increased feature space and computational intensity.
      Alternatively, recursive partitioning approaches, such as random forests, have
      gained popularity in high-dimensional genetic association studies. In this
      article, we propose a U-Statistic-based random forest approach, referred to as
      Forest U-Test, for genetic association studies with quantitative traits. Through
      simulation studies, we showed that the Forest U-Test outperformed exiting
      methods. The proposed method was also applied to study Cannabis Dependence (CD),
      using three independent datasets from the Study of Addiction: Genetics and
      Environment. A significant joint association was detected with an empirical p
      value less than 0.001. The finding was also replicated in two independent
      datasets with p-values of 5.93e-19 and 4.70e-17, respectively.

PMID- 22652672
TI  - Rosuvastatin effect on intima media thickness in adult vs elderly patients.
AB  - The benefits of cardiovascular therapies such as statins for the treatment of
      atherosclerosis have been well documented. Many studies have demonstrated
      important benefits in patients with asymptomatic carotid atherosclerosis. We have
      evaluated the effect of low dose of rosuvastatin on asymptomatic carotid
      atherosclerosis in elderly versus adult subjects. Among 640 participants in the
      Asymptomatic Carotid Atherosclerotic Disease In Manfredonia Study (ACADIM Study)
      forty-five patients (21 adults, 24 elderly) with hypercholesterolemia and
      asymptomatic carotid atherosclerosis on baseline carotid ultrasound investigation
      (CUI) were examined with repeat CUI after one treatment year with rosuvastatin
      (ROS) (10 mg/day). Total and low density lipoprotein cholesterol decreased
      significantly (p<0.001) while high density lipoprotein cholesterol increased
      significantly (p<0.001) during the intervention. Mean decrease in carotid intima
      media thickness (CIMT) of the right and left common carotid arteries were higher
      in adult versus elderly subjects (p<0.04 for each), even if in both group there
      was a significant regression in carotid atherosclerosis respect to baseline
      values (P<0.001). These results confirm the reduction in IMT of the CCAs in
      response to ROS at a low dose in a one-year treatment period, even if in elderly
      subjects this effect is lower respect to adult. The treatment of asymptomatic
      carotid atherosclerosis defined by CIMT started in the adult age is more
      effective.

PMID- 22652674
TI  - P4 down-regulates Jagged2 and Notch1 expression during primordial
      folliculogenesis.
AB  - Nest breakdown and primordial folliculogenesis of the mouse ovary can be
      inhibited by progesterone (P4) and Notch signaling inhibitors. However, the
      relationship between these two signals during this process remains unknown. In
      the present study, transcript levels of Jagged2, Notch1, and their target, Hey2,
      increased markedly in ovaries during the beginning stage of folliculogenesis
      (17.5 days post coitus (dpc) to birth). Maternal P4 levels decreased
      simultaneously. We found that maternal midpregnancy P4 levels significantly
      inhibited Jagged2, Notch1, and Hey2 expression, and follicle formation in vitro.
      Maintaining high maternal P4 levels by daily injection also significantly
      suppressed the expression of Jagged2, Notch1, and Hey2, and follicle formation
      during late pregnancy. Based on immunohistochemistry, Jagged2 was localized in
      oocytes and Notch1 was strongly stained in pre-granulosa cells in 19.5 dpc
      ovaries. Suppression of their function by antibody addition and RNAi markedly
      inhibited nest breakdown and follicle formation. Taken together, these results
      demonstrate that maternal P4 levels during midpregnancy can inhibit the
      expression of Jagged2 and Notch1, which are involved in primordial
      folliculogenesis, in the mouse fetal ovary.

PMID- 22652673
TI  - Emotional dysfunction as a marker of bipolar disorders.
AB  - BACKGROUND: Assessment of emotional reactivity, defined as rapid emotional
      responses to salient environmental events, has been neglected in mood disorders.
      This article reviews data showing the relevance of using emotional reactivity to
      better characterize bipolar mood episodes. METHOD: We reviewed clinical data on
      emotional reactivity during all phases of bipolar disorders (euthymic, manic,
      mixed and depressive states) and brain-imaging, neurochemical, genetic studies
      related to emotional reactivity disturbances. RESULT: Euthymic bipolar patients
      show mild abnormalities (hypersensitivity to emotional stimuli and higher
      arousability) in comparison to controls. Both manic and mixed states are
      characterized by a significant increase in emotional reactivity. Furthermore,
      emotional reactivity may discriminate between two types of bipolar depression,
      the first being characterized by emotional hypo-reactivity and global behavioral
      inhibition, the second by emotional hyper-reactivity. Brain-imaging studies can
      help to identify the underlying mechanisms involved in disturbances of emotional
      reactivity. CONCLUSION: Emotional reactivity can be used to refine more
      homogeneous pathophysiological subtypes of mood episodes. Future research should
      explore possible correlations between biomarkers, response to treatments and
      these clinical phenotypes.

PMID- 22652675
TI  - CD24, COX-2, and p53 in epithelial ovarian cancer and its clinical significance.
AB  - Epithelial ovarian cancer (EOC) prognosis is associated with International
      Federation of Gynecology and Obstetrics (FIGO) staging, cancer cell
      classification, patient age, and residual tumor size. However, the molecular
      markers for predicting EOC prognosis remain to be explored. In this study, we
      investigated the expression of CD24, COX-2, and p53 in EOC, and their
      relationships to clinical prognosis. We found that the expression of CD24 was
      detected in the cell membrane in 90.6 percent (58/64) of EOC cases and in the
      cytoplasm in 54.7 percent (35/64) of EOC cases; 78.6 percent (11/14) cases of
      borderline tumors had CD24-positive staining in the cell membrane. All 9 cases of
      benign tumors were negative for CD24 staining. Expression of CD24 correlated with
      the nuclear expression of p53, but not with the expression of COX-2.
      Overexpression of CD24 is an independent factor associated with tumor metastasis,
      a low survival rate, and a short survival time. Our results suggest that CD24 may
      be a valuable molecular marker for predicting prognoses of patients with EOC.

PMID- 22652676
TI  - The opposing roles of anti-angiogenic factors in cancer and preeclampsia.
AB  - Hypertensive disorders of pregnancy such as preeclampsia present an increasing
      source of concern during gestation and accumulating evidence suggests there are
      long-term effects on the subsequent health of the mother and child. While
      formerly preeclamptic women have increased risk for later cardiovascular disease,
      they appear to have decreased risk of some cancers. Recent investigations have
      revealed exciting insights into potential mechanisms underlying the pathogenesis
      of preeclampsia and some of these findings may bear relevance to the attenuated
      cancer risk reported in the literature. Placental ischemia, regarded as a primary
      initiating factor in preeclampsia, results in elevated levels of factors such as
      soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin/CD105 (sEng)
      that generate profound effects on the vascular endothelium and cardiovascular
      function. Further, these factors may also influence development of susceptible
      organs such as the mammary. Moreover, recent evidence suggests these molecules
      may be regulated by factors derived from cigarette smoke. Taken together,
      elucidating mechanisms linking placental ischemia, endothelial function and
      subsequent cancer risk is an important step towards identifying novel therapies
      for cancer.

PMID- 22652677
TI  - A score-statistic approach for determining threshold values in QTL mapping.
AB  - Issues in determining the threshold values of QTL mapping are often investigated
      for the backcross and F2 populations with relatively simple genome structures so
      far. The investigations of these issues in the progeny populations after F2
      (advanced populations) with relatively more complicated genomes are generally
      inadequate. As these advanced populations have been well implemented in QTL
      mapping, it is important to address these issues for them in more details. Due to
      an increasing number of meiosis cycle, the genomes of the advanced populations
      can be very different from the backcross and F2 genomes. Therefore, special
      devices that consider the specific genome structures present in the advanced
      populations are required to resolve these issues. By considering the differences
      in genome structure between populations, we formulate more general score test
      statistics and gaussian processes to evaluate their threshold values. In general,
      we found that, given a significance level and a genome size, threshold values for
      QTL detection are higher in the denser marker maps and in the more advanced
      populations. Simulations were performed to validate our approach.

PMID- 22652678
TI  - Irritable bowel syndrome: the role of gut neuroendocrine peptides.
AB  - Irritable bowel syndrome (IBS) is a common chronic disorder with a prevalence
      ranging from 5 to 10 percent of the world's population. This condition is
      characterised by abdominal discomfort or pain, altered bowel habits, and often
      bloating and abdominal distension. IBS reduces quality of life in the same degree
      of impairment as major chronic diseases such as congestive heart failure and
      diabetes and the economic burden on the health care system and society is high.
      Abnormalities have been reported in the neuroendocrine peptides/amines of the
      stomach, small- and large intestine in patients with IBS. These abnormalities
      would cause disturbances in digestion, gastrointestinal motility and visceral
      hypersensitivity, which have been reported in patients with IBS. These
      abnormalities seem to contribute to the symptom development and appear to play a
      central role in the pathogenesis of IBS. Neuroendocrine peptides/amines are
      potential tools in the treatment and diagnosis of IBS. In particular, the cell
      density of duodenal chromogranin A expressing cells appears to be a good
      histopathological marker for the diagnosis of IBS with high sensitivity and
      specificity.

PMID- 22652681
TI  - An organ system based approach to prognosis in advanced melanoma.
AB  - Previous models to study the biology of melanoma have focused on individual
      factors, such as proliferative and invasive capacity, the microenvironment,
      angiogenesis, or systemic immune dysfunction. However, all of these factors
      contribute to melanoma progression in concert. One physiologic phenomenon that
      typifies the coordination of these processes is placental development,
      characterized by trophoblast proliferation, invasion into decidual tissues,
      angiogenesis, and transient organ system-based immune evasion. Herein, we explore
      expression of 34 proteins involved in placentation and determine their
      association with an established prognostic factor, tumor infiltrating lymphocytes
      (TILs), in a 118-patient tumor microarray (TMA). Melanoma expression of CD58 and
      galectin-9 independently predicted for a favorable prognosis. Patients could be
      categorized into three clusters based upon patterns of protein expression and
      TILs. Patients in Cluster 2 demonstrated frequent TILs and superior overall
      survival. Pathway enrichment using MetaCore (trademark) from GeneGo, a Thompson
      Reuters company, showed that TIMP2 and CD44 were expressed more frequently within
      Cluster 2 patients, suggesting a potential association with TILs. A subset of
      melanoma patients appear to lack an organized immune response to the tumor, which
      portends a poor prognosis.

PMID- 22652679
TI  - A high-throughput screen to identify inhibitors of SOD1 transcription.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disease.
      Approximately 20 percent of familial ALS cases are caused by mutations in the
      Cu/Zn superoxide dismutase (SOD1) gene. Rodents expressing mutant SOD1 transgenes
      develop progressive, fatal motor neuron disease and disease onset and progression
      is dependent on the level of SOD1. We investigated the possibility that a
      reduction in SOD1 protein may be of therapeutic benefit in ALS and screened
      30,000 compounds for inhibition of SOD1 transcription. The most effective
      inhibitor identified was N-{4-[4-(4-methylbenzoyl)-1-piperazinyl]phenyl}-2
      thiophenecarboxamide (Compound ID 7687685), which in PC12 cells showed an EC50 of
      10.6 microM for inhibition of SOD1 expression and an LD50 more than 30 microM.
      This compound was subsequently shown to reduce endogenous SOD1 levels in HeLa
      cells and to exhibit a modest reduction of SOD1 protein levels in mouse spinal
      cord tissue. These data suggest that the efficacy of compound 7687685 as an
      inhibitor of SOD1 gene expression is not likely to be clinically useful, although
      the strategy reported could be applied broadly to screening for small molecule
      inhibitors of gene expression.

PMID- 22652680
TI  - Bladder cancer documentation of causes: multilingual questionnaire, 'bladder
      cancer doc'.
AB  - There is a considerable discrepancy between the number of identified occupational
      related bladder cancer cases and the estimated numbers particularly in emerging
      nations or less developed countries where suitable approaches are less or even
      not known. Thus, within a project of the World Health Organisation Collaborating
      Centres in Occupational Health, a questionnaire of the Dortmund group, applied in
      different studies, was translated into more than 30 languages (Afrikaans, Arabic,
      Bengali, Chinese, Czech, Dutch, English, Finnish, French, Georgian, German,
      Greek, Hindi, Hungarian, Indonesian, Italian, Japanese, Kannada, Kazakh, Kirghiz,
      Korean, Latvian, Malay, Persian (Farsi), Polish, Portuguese,
      Portuguese/Brazilian, Romanian, Russian, Serbo-Croatian, Slovak, Spanish,
      Spanish/Mexican, Tamil, Telugu, Thai, Turkish, Urdu, Vietnamese). The bipartite
      questionnaire asks for relevant medical information in the physician's part and
      for the occupational history since leaving school in the patient's part.
      Furthermore, this questionnaire is asking for intensity and frequency of certain
      occupational and non-occupational risk factors. The literature regarding
      occupations like painter, hairdresser or miner and exposures like carcinogenic
      aromatic amines, azo dyes, or combustion products is highlighted. The
      questionnaire is available on www.ifado.de/BladderCancerDoc.

PMID- 22652682
TI  - Gene expression in visceral and subcutaneous adipose tissue in overweight women.
AB  - Excess weight and obesity are common health problems with multifactorial and
      polygenic causes. Abdominal or visceral obesity is associated with a higher risk
      of obesity related complications. The aim of the study was to evaluate
      differentially expressed genes in visceral adipose tissue (VAT) and subcutaneous
      adipose tissue (SAT) of 10 overweight women undergoing elective laparoscopic
      cholecystectomy. Following expression profiling using microarrays, a set of 294
      genes that exhibited differential expression between VAT and SAT was further
      analyzed to test the functional correlation of gene sets using the Gene Set
      Enrichment Analysis method. To confirm the functional pathways involved in
      differential expression between SAT and VAT, additional pathway analysis was done
      using the GeneGo MetaCore software and the Ingenuity Pathway Analysis. Ten
      differentially expressed genes were selected according to the microarray data,
      with seven exhibiting significant differential expression in the RT-PCR
      experiments. The data from this preliminary study suggest enrichment of
      inflammation and oxidative stress related pathways in VAT, while insulin
      homeostasis pathways as well as pathways pertaining to several growth factors are
      enriched in SAT.

PMID- 22652683
TI  - Effects of in utero endotoxemia on the ovine fetal brain: a model for
      schizophrenia?
AB  - Infections during pregnancy can adversely affect the development of the fetal
      brain. This may contribute to disease processes such as schizophrenia in later
      life. Changes in the (cyto-) architecture of the anterior cingulate cortex (ACC),
      particularly in GABA-ergic interneurons, play a role in the pathogenesis of
      schizophrenia. We hypothesized that exposure to infection during pregnancy could
      result in cyto-architectural changes in the fetal ACC, similar to the
      pathogenesis seen in schizophrenia. Fetal sheep of 110 days GA (term=150 days GA)
      received an intravenous injection of 100 ng or 500 ng lipopolysaccharide (LPS) or
      saline as control. After delivery at 113 days GA, the cyto-architecture of the
      cingulate cortex (CC) was examined by immunohistochemistry. High dose LPS
      exposure resulted in a decreased density of GFAP-, calbindin D-28K- and
      parvalbumin-immunoreactive cells in the CC. In addition, these cells and
      calretinin-immunoreactive cells showed a changed morphology with reduced cell
      processes. This study provides further evidence that intra-uterine endotoxemia
      can induce changes in the fetal brain which correspond with changes seen in
      schizophrenia.

PMID- 22652684
TI  - Stem cell theory for the pathogenesis of endometriosis.
AB  - Proposed hypothetical causes of endometriosis include retrograde menstruation,
      lymphatic and vascular metastasis, iatrogenic direct implantation, coelomic
      metaplasia, embryonic rest, and mesenchymal cell differentiation (induction).
      Each theory, individually, fails to account for all types of endometriotic
      lesions, thereby implicating combined and/or type-specific mechanisms. Recent
      evidence supports the presence of endometrial stem/progenitor cells and their
      possible involvement in eutopic endometrial regeneration and differentiation.
      Thus an additional novel mechanism for the origin of endometriotic lesions is
      that they arise from ectopic endometrial stem/progenitor cells.

PMID- 22652685
TI  - Modeling disease using three dimensional cell culture: multi-lumen and inverted
      cyst phenotypes.
AB  - Three-dimensional cell culture provides a unique system to investigate intrinsic
      mechanisms and micro environmental cues involved in the morphogenesis of
      epithelial glandular architectures.  While this culture system allows insight
      into normal tissue development, it is also is readily amenable to manipulations
      that permit cellular modeling of various disease states.  Here, we discuss a
      range of cellular and genetic alterations that result in two distinct cyst
      phenotypes, the multi-lumen cyst and the inverted cyst, both of which involve
      defects in cell polarity and lumen formation.  Multi-lumen cyst formation results
      from disturbances in the mechanisms that regulate cell polarity, apical assembly,
      and the rate of lumen clearance.  In the inverted cyst, the apical domain is
      oriented adjacent to the matrix, markedly affecting the morphogenic cues the
      matrix provides for cystogenesis.  Both of these abnormal glandular phenotypes
      are highly reminiscent of histological patterns used to classify a number of
      diseases.  A better understanding of the causes of multi-lumen and inverted cysts
      will provide insights into the origin and progression of epithelial diseases,
      potentially leading to the development of new therapies.

PMID- 22652688
TI  - Mediators and cytokines in persistent allergic rhinitis and nonallergic rhinitis
      with eosinophilia syndrome.
AB  - BACKGROUND: Patients with nonallergic rhinitis with eosinophilia syndrome (NARES)
      show typical symptoms of persistent allergic rhinitis (PAR). The aim of the
      present study was to compare nasal cytokine patterns between NARES and PAR.
      METHODS: Nasal secretions of 31 patients suffering from NARES, 20 patients with
      PAR to house dust mite and 21 healthy controls were collected using the cotton
      wool method and analyzed for interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL
      7, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating
      factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-gamma
      (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant
      protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta) by Bio
      Plex Cytokine Assay as well as eosinophil cationic protein (ECP) and tryptase by
      UniCAP-FEIA. RESULTS: NARES and PAR presented elevated levels of tryptase, while
      ECP was markedly increased solely in NARES compared to both the controls and PAR.
      Elevated levels of IL-1beta, IL-17, IFN-gamma, TNF-alpha and MCP-1 were found in
      NARES compared to the controls as well as PAR. MIP-1beta was elevated in NARES
      and PAR, while IL-4, IL-6 and G-CSF showed increased levels in NARES, and IL- 5
      was elevated in PAR only. CONCLUSIONS: In patients with NARES and PAR,
      eosinophils and mast cells appear to be the pivotal cells of inflammation,
      reflected by high levels of tryptase and ECP as well as IL-5 and GM-CSF as
      factors for eosinophil migration and survival. The elevated levels of
      proinflammatory cytokines in NARES may indicate the chronic, self-perpetuating
      process of inflammation in NARES which seems to be more pronounced than in PAR.
      IL-17 might be a factor for neutrophilic infiltration or be responsible for
      remodeling processes in NARES.

PMID- 22652689
TI  - Indoor air in schools and lung function of Austrian school children.
AB  - The Children's Environment and Health Action Plan for Europe (CEHAPE) of WHO
      focuses (inter alia) on improving indoor environments where children spend most
      of their time. At present, only little is known about air pollution in schools
      and its effect on the lung function of school children. Our project was set up as
      an Austrian contribution to CEHAPE. In a cross-sectional approach, differences in
      indoor pollution in nine elementary all-day schools were assessed and 34 of these
      pollutants were analyzed for a relationship with respiratory health determined by
      spirometry using a linear regression model. Overall 596 children (aged 6-10
      years) were eligible for the study. Spirometry was performed in 433 children.
      Socio-economic status, area of living (urban/rural), and smoking at home were
      included in the model as potential confounders with school-related average
      concentration of air pollutants as the variable of primary interest. A negative
      association with flow volumes (MEF(75)) was found for formaldehyde in air
      samples, benzylbutylphthalate and the sum of polybrominated diphenylethers in
      school dust. FVC and FEV(1) were negatively associated with ethylbenzene and
      xylenes in air samples and tris(1,3-dichlor-2-propyl)-phosphate on particulates.
      Although, in general, the quality of school indoor air was not worse than that
      reported for homes, effects on the respiratory health of children cannot be
      excluded. A multi-faceted strategy to improve the school environment is needed.

PMID- 22652690
TI  - Influence of nanoconfinement on morphology and dehydrogenation of the Li11BD4
      Mg(11BD4)2 system.
AB  - The decomposition of a nanoconfined mixture of lithium-magnesium borohydride,
      Li(11)BD(4)-Mg((11)BD(4))(2), has been investigated and compared to the
      corresponding mixture in the bulk form. The systems were investigated by thermal
      analysis, small-angle neutron scattering, (11)B nuclear magnetic resonance and
      transmission electron microscopy. The dehydrogenation temperatures decreased by
      up to 60  degrees C in the nanoconfined system, with gas evolution following
      different steps, compared to the behaviour of the bulk material under the same
      conditions. Most importantly, desorption from the nanoconfined hydride proceeds
      without formation of diborane, B(2)D(6), which evolves from the bulk mixture.
      From small-angle neutron scattering, differences in morphology between the bulk
      and the nanoconfined systems are also demonstrated. Evidence of a complete
      decomposition has been found in the nanoconfined system, after heating up to 460 
      degrees C. Furthermore, (11)B NMR data show that nanoconfinement inhibits the
      formation of dodecaborane, [B(12)D(12)](2-), during decomposition, a result which
      is important for practical applications of borohydrides.

PMID- 22652691
TI  - Mixed monolayer protected gold atom-oxide cluster synthesis and characterization.
AB  - Small atomic gold clusters in solution, Au(n), stabilized by cetyl
      trimethylammonium bromide (CTAB) and cysteine, have been synthesized
      potentiodynamically in quiescent aqueous solutions. The electrodissolution of
      gold to gold ions during an anodic scan and subsequent cluster formation during a
      cathodic scan in underpotential (UPDD) and overpotential dissolution-deposition
      (OPDD) regions were studied. The experimental potentiodynamic I-E profiles and
      chronoamperometric i-t transients are fit into reported theoretical models of
      adsorption and electrocrystallization. The plausible application of
      clusters/cluster film to cysteine sensing based on fluorescence quenching and
      square wave stripping voltammetry is demonstrated.

PMID- 22652692
TI  - Acute pulmonary vein isolation is achieved by a combination of reversible and
      irreversible atrial injury after catheter ablation: evidence from magnetic
      resonance imaging.
AB  - BACKGROUND: Pulmonary vein reconnection after pulmonary vein isolation is common
      and is usually associated with recurrences of atrial fibrillation. We used
      cardiac magnetic resonance imaging after radiofrequency ablation to investigate
      the hypothesis that acute pulmonary vein isolation results from a combination of
      irreversible and reversible atrial injury. METHODS AND RESULTS: Delayed
      enhancement (DE; representing areas of acute tissue injury/necrosis) and T2
      weighted (representing tissue water content, including edema) cardiac magnetic
      resonance scans were performed before, immediately after (acute), and later than
      3 months (late) after pulmonary vein isolation in 25 patients with paroxysmal
      atrial fibrillation undergoing wide-area circumferential ablation. Images were
      analyzed as pairs of pulmonary veins to quantify the percentage of
      circumferential antral encirclement composed of DE, T2, and combined DE+T2
      signal. Fourteen of 25 patients were atrial fibrillation free at 11-month follow
      up (interquartile range, 8-16 months). These patients had higher DE (71+/-6.0%)
      and lower T2 signal (72+/-7.8%) encirclement on the acute scans compared with
      recurrences (DE, 55+/-9.1%; T2, 85+/-6.3%; P<0.05). Patients maintaining sinus
      rhythm had a lesser decline in DE between acute and chronic scans compared with
      recurrences (71+/-6.0% and 60+/-5.8% versus 55+/-9.1% and 34+/-7.3%,
      respectively). The percentage of encirclement by a combination of DE+T2 was
      almost similar in both groups on the acute scans (atrial fibrillation free, 89+/
      5.4%; recurrences, 92+/-4.8%) but different on the chronic scans (60+/-5.7%
      versus 34+/-7.3%). CONCLUSIONS: The higher T2 signal on acute scans and greater
      decline in DE on chronic imaging in patients with recurrences suggest that they
      have more reversible tissue injury, providing a potential mechanism for pulmonary
      vein reconnection, resulting in arrhythmia recurrence.

PMID- 22652693
TI  - WRAD: enabler of the SET1-family of H3K4 methyltransferases.
AB  - Methylation of histone H3 at lysine 4 (H3K4) is a conserved feature of active
      chromatin catalyzed by methyltransferases of the SET1-family (SET1A, SET1B, MLL1,
      MLL2, MLL3 and MLL4 in humans). These enzymes participate in diverse gene
      regulatory networks with a multitude of known biological functions, including
      direct involvement in several human disease states. Unlike most lysine
      methyltransferases, SET1-family enzymes are only fully active in the context of a
      multi-subunit complex, which includes a protein module comprised of WDR5, RbBP5,
      ASH2L and DPY-30 (WRAD). These proteins bind in close proximity to the catalytic
      SET domain of SET1-family enzymes and stimulate H3K4 methyltransferase activity.
      The mechanism by which WRAD promotes catalysis involves elements of allosteric
      control and possibly the utilization of a second H3K4 methyltransferase active
      site present within WRAD itself. WRAD components also engage in physical
      interactions that recruit SET1-family proteins to target sites on chromatin.
      Here, the known molecular mechanisms through which WRAD enables the function of
      SET1-related enzymes will be reviewed.

PMID- 22652694
TI  - Organization of Mhc class II A and B genes in the tilapiine fish Oreochromis.
AB  - Perch-like fishes of the family Cichlidae are models for the study of speciation.
      An important tool in these studies is the major histocompatibility complex (Mhc)
      and its organization. The present study takes the first step toward the
      elucidation of the Mhc class II gene organization in the tilapiine fish
      Oreochromis niloticus (Orni). Using class II A- and class II B-specific probes,
      Mhc-bearing clones were identified and isolated from a bacterial artificial
      chromosome (BAC) library. The analysis of these clones by a combination of
      molecular, genetic-mapping, and phylogenetic methods led to the identification of
      nine class II A and 15 class II B loci. Genes at these loci constitute two
      families, which we designate as class IIa and class IIb families. Each of the
      families contains A and B loci. Some genes in both families are expressed and
      functional. The two families differ in their chromosomal location (they are
      unlinked) and their mode of evolution. The class IIa family genes are conserved
      across different teleost taxonomical orders, whereas the class IIb family genes
      are apparently products of multiple, more recent, rounds of gene duplications.
      The rounds established at least five monophyletic groups of genes. The founding
      unit of each monophyletic group might have been a pair of class II A and B loci.

PMID- 22652699
TI  - A slate grey rash.

PMID- 22652701
TI  - Vertical and tilted Ag-NPs@ZnO nanorods by plasma-enhanced chemical vapour
      deposition.
AB  - Supported ZnO nanorods have been prepared at 405 K by plasma-enhanced chemical
      vapour deposition (PECVD) using diethylzinc as precursor, oxygen plasma and
      silver as the promotion layer. The nanorods are characterized by a hollow and
      porous microstructure where partially percolated silver nanoparticles are
      located. By changing different deposition parameters like the thickness of the
      silver layer, the type of oxidation pretreatment or the geometry of the
      deposition set-up, the length, the width and the tilting angle of the nanorods
      with respect to the substrate can be modified. Other nanostructures like
      nanobushes, zigzag linear structures and stacked bilayers with nanocolumns of
      TiO(2) can also be prepared by adjusting the deposition conditions. A
      phenomenological model relying on the assessment of the diverse nanostructure
      morphologies and the evidence provided by an in situ x-ray photoelectron
      spectroscopy (XPS) experiment has been proposed to describe their formation
      mechanism. From this analysis it is deduced that the effect of the electrical
      field of the plasma sheath, the high mobility of silver and silver oxide, and the
      diffusion of the precursor molecules are some of the critical factors that must
      converge by the formation of the nanorods.

PMID- 22652695
TI  - Killer-cell immunoglobulin-like receptors (KIR) in severe A (H1N1) 2009 influenza
      infections.
AB  - Introduction of a novel influenza virus into the human population leads to the
      occurrence of pandemic events, such as the one caused by pandemic influenza A
      (H1N1) 2009 virus. The severity of infections caused by this virus in young
      adults was greater than that observed in patients with seasonal influenza. Fatal
      cases have been associated with an abnormal innate, proinflammatory immune
      response. A critical role for natural killer cells during the initial responses
      to influenza infections has been suggested. In this study, we assessed the
      association of killer-cell immunoglobulin-like receptors (KIRs) with disease
      severity by comparing KIR gene content in patients with mild and severe pandemic
      influenza virus infections to a control group. We found that activator (KIR3DS1
      and KIR2DS5) and inhibitory (KIR2DL5) genes, encoded in group B haplotypes
      containing the cB01, cB03 and tB01 motifs, are associated with severe pandemic
      influenza A (H1N1) 2009 infections. Better understanding of how genetic
      variability contributes to influenza virus pathogenesis may help to the
      development of immune intervention strategies aiming at controlling the severity
      of disease.

PMID- 22652700
TI  - Tobacco modalities used and outcome in patients with acute coronary syndrome: an
      observational report.
AB  - AIM: The authors evaluated the prevalence and effect of the various tobacco use
      modalities among patients presenting with acute coronary syndrome (ACS) and
      compared them with non-tobacco and ex-tobacco users. METHODS: An analysis of the
      2nd Gulf Registry of Acute Coronary Events conducted between October 2008 and
      June 2009 and which included 7930 consecutive patients hospitalised with ACS was
      made. Patients initially were divided into non-tobacco users, ex-tobacco users
      and current tobacco users. Subanalysis according to the tobacco modality used was
      subsequently made: cigarette, waterpipe or smokeless tobacco users. RESULTS:
      Overall, 2834 (36%) patients were current tobacco users, 306 (3.9%) patients were
      waterpipe smokers and 240 patients (3%) were oral tobacco users. When compared
      with non-tobacco and ex-tobacco users, overall current tobacco users were
      younger, more likely to be male subjects and less likely to have diabetes
      mellitus, hypertension and dyslipidaemia. Mortality rate (p=0.001) and overall
      cardiovascular events (p=0.001) were lower among current tobacco users when
      compared with the other two groups. After adjustment for baseline variables,
      tobacco use was not an independent predictor of adverse events. Subset analysis
      demonstrates oral tobacco users and waterpipe smokers were older and more likely
      to be women when compared with cigarette smokers. Among the various tobacco
      groups, inhospital mortality rates were significantly higher among the waterpipe
      smokers when compared with the other two groups. CONCLUSIONS: Clinical
      characteristics and outcomes of ACS patients depend on the tobacco modality used.
      Further studies are required to evaluate the impact of emerging tobacco use
      modalities on patients with coronary artery disease.

PMID- 22652702
TI  - Quantum chemistry simulation on quantum computers: theories and experiments.
AB  - It has been claimed that quantum computers can mimic quantum systems efficiently
      in the polynomial scale. Traditionally, those simulations are carried out
      numerically on classical computers, which are inevitably confronted with the
      exponential growth of required resources, with the increasing size of quantum
      systems. Quantum computers avoid this problem, and thus provide a possible
      solution for large quantum systems. In this paper, we first discuss the ideas of
      quantum simulation, the background of quantum simulators, their categories, and
      the development in both theories and experiments. We then present a brief
      introduction to quantum chemistry evaluated via classical computers followed by
      typical procedures of quantum simulation towards quantum chemistry. Reviewed are
      not only theoretical proposals but also proof-of-principle experimental
      implementations, via a small quantum computer, which include the evaluation of
      the static molecular eigenenergy and the simulation of chemical reaction
      dynamics. Although the experimental development is still behind the theory, we
      give prospects and suggestions for future experiments. We anticipate that in the
      near future quantum simulation will become a powerful tool for quantum chemistry
      over classical computations.

PMID- 22652707
TI  - Twenty years of bicarbonate solutions.
AB  - For many years, lactate has been used successfully as a buffer in peritoneal
      dialysis solutions although its effectiveness in the correction of uremic
      acidosis and its biocompatibility on peritoneal resident cells have been
      questioned. In addition, some investigators have suggested other potential
      adverse metabolic effects resulting from the unphysiologically high lactate flux
      into the body during CAPD. These potential problems associated with lactate
      containing CAPD solution prompted the search for alternative buffer-containing
      solutions. Bicarbonate, the physiological buffer, was considered when the problem
      of calcium and magnesium carbonate solubility was solved by the use of a two
      compartment bag system allowing the mixing of bicarbonate and divalent cations
      immediately before infusion. The long-term tolerance, safety, efficacy and
      therapeutic value of a bicarbonate-buffered peritoneal dialysis solution have
      been evaluated for about 15 years. RCT studies demonstrated a benefit for acid
      base improvement, while observational reports showed other clinical effects such
      as a preservation of residual renal function, less inflammatory effect and
      peritonitis prevention. In addition, there is a consensus that local
      biocompatibility is improved. Therefore, as bicarbonate is the physiological
      buffer of the body, it should become the solution of choice in PD patients.

PMID- 22652704
TI  - Natriuretic peptide receptor guanylyl cyclase-A protects podocytes from
      aldosterone-induced glomerular injury.
AB  - Natriuretic peptides produced by the heart in response to cardiac overload exert
      cardioprotective and renoprotective effects by eliciting natriuresis, reducing
      BP, and inhibiting cell proliferation and fibrosis. These peptides also
      antagonize the renin-angiotensin-aldosterone system, but whether this mechanism
      contributes to their renoprotective effect is unknown. Here, we examined the
      kidneys of mice lacking the guanylyl cyclase-A (GC-A) receptor for natriuretic
      peptides under conditions of high aldosterone and high dietary salt. After 4
      weeks of administering aldosterone and a high-salt diet, GC-A knockout mice, but
      not wild-type mice, exhibited accelerated hypertension with massive proteinuria.
      Aldosterone-infused GC-A knockout mice had marked mesangial expansion, segmental
      sclerosis, severe podocyte injury, and increased oxidative stress. Reducing the
      BP with hydralazine failed to lessen such changes; in contrast, blockade of the
      renin-angiotensin-aldosterone system markedly reduced albuminuria, ameliorated
      podocyte injury, and reduced oxidative stress. Furthermore, treatment with the
      antioxidant tempol significantly reduced albuminuria and abrogated the histologic
      changes. In cultured podocytes, natriuretic peptides inhibited aldosterone
      induced mitogen-activated protein kinase phosphorylation. Taken together, these
      results suggest that renoprotective properties of the endogenous natriuretic
      peptide/GC-A system may result from the local inhibition of the renin-angiotensin
      aldosterone system and oxidative stress in podocytes.

PMID- 22652705
TI  - Activation of MAPK/PI3K/SMAD pathways by TGF-beta(1) controls differentiation of
      radial glia into astrocytes in vitro.
AB  - The major neural stem cell population in the developing cerebral cortex is the
      radial glia cells, which generate neurons and glial cells. The mechanisms that
      modulate the maintenance of the radial glia stem cell phenotype, or its
      differentiation, are not completely elucidated. We previously demonstrated that
      transforming growth factor-beta(1) (TGF-beta(1)) promotes radial glia
      differentiation into astrocytes in vitro [Glia 2007;55:1023-1033]. Here we
      investigated the intracellular signaling pathways involved in the TGF-beta(1)
      induced radial glia fate commitment. We demonstrate that the mechanisms
      underlying the TGF-beta(1) effect on radial glia cell differentiation or
      progenitor potential maintenance diverge. Whereas radial glia differentiation
      into astrocytes is mediated by the activation of the MAPK signaling pathway,
      neurogenesis is modulated by different levels of PI3K and SMAD2/3 activity. Our
      work demonstrates that radial glia cells are a heterogeneous population and a
      potential target of TGF-beta(1), and suggests that its effect on radial glia fate
      commitment is mediated by the recruitment of a complex multipathway mechanism
      that controls astrocyte and neuronal generation in the developing cerebral
      cortex.

PMID- 22652708
TI  - Peritoneal dialysis solution and nutrition.
AB  - 20-70% of peritoneal dialysis patients have some signs of malnutrition. Anorexia,
      protein and amino acid losses in dialysate, advanced age of elderly patients,
      inflammation and cardiac failure are among the main causes. Modern dialysis
      solutions aim to reduce these causes, but none of them is without side effects:
      glucose is relatively safe and brings additional energy but induces anorexia and
      lipid abnormalities, amino acids compensate dialysate losses but may increase
      uremia and acidosis, icodextrin helps control hyperhydration and chronic heart
      failure and minimizes glucose side effects, but may sometimes cause inflammation,
      and poly chamber bags allow the replacement of lactate by bicarbonate and are
      more biocompatible, decrease GDP, induce less inflammation and have a better
      effect on nutritional status. However, it appears that the management of
      nutrition with the different solutions available nowadays necessitates various
      combinations of solutions adapted to different patient profiles and there is not
      actually a single universal solution to minimize malnutrition in peritoneal
      dialysis patients.

PMID- 22652709
TI  - Alternative dialysis strategies with icodextrin.
AB  - Proper volume management continues to be a major challenge in patients requiring
      renal replacement therapy. In patients performing peritoneal dialysis the
      introduction of icodextrin represented a major advance in this effort. Recent
      studies have demonstrated a potential role for the use of novel dialysis
      strategies employing icodextrin to further enhance ultrafiltration and to improve
      cardiac indices in patients with ultrafiltration failure. These alternative
      strategies include the use of icodextrin in non-traditional patient populations
      (low transporters), the simultaneous use of glucose-based and icodextrin
      solutions in combination, and the use of icodextrin twice daily rather than for
      just a single dwell. This paper will briefly review the current status of these
      alternative dialysis strategies with icodextrin. In addition, the potential role
      for icodextrin to decrease postoperative adhesions will be discussed as well.

PMID- 22652706
TI  - Antifungal therapy in children: an update.
AB  - Invasive fungal infections are a common problem in children affected by primary
      or secondary immunodeficiencies. Thanks to an increased knowledge about their
      mechanisms of action and their pharmacokinetic and toxicity profiles, the use of
      these drugs in common and uncommon invasive infections in immunocompromised
      children has improved over the last decades. Choosing the most appropriate
      antifungal drug is a serious challenge for any clinician, also considering that,
      in most cases, therapy has to be started before cultures are available, the
      choice being driven by clinical symptoms and statistical criteria only. In this
      study, we performed a systematic review of literature, providing antifungal
      treatment recommendations for paediatric patients which can help clinicians find
      the most suitable treatment for each specific case. Principal antifungal drugs
      ranging from first-generation antimycotics to the latest molecules-are classified
      according to their targets, and of each group, the pharmacokinetic profile,
      clinical indications and side effects are extensively described.

PMID- 22652710
TI  - Are current peritoneal dialysis solutions adequate for pediatric use?
AB  - Peritoneal dialysis (PD) is the treatment modality of choice in pediatric CKD5D
      patients awaiting renal transplantation. Facing many decades of renal replacement
      therapy long term preservation of peritoneal membrane function is of particular
      importance in this patient group. Whereas conventional PD fluids induce severe
      morphological and functional alterations of the peritoneal membrane within a few
      years, reduction of glucose degradation product content by multichamber systems,
      replacement of glucose by icodextrin and amino acids, and of lactate by
      bicarbonate at a neutral to physiological pH are expected to preserve peritoneal
      membrane integrity. Based on numerous in vitro, experimental and clinical
      studies, the European Pediatric Dialysis Working Group recommended the use of low
      glucose degradation product solutions whenever possible. Icodextrin is considered
      a useful option, in particular in children with sodium and water overload, even
      though infants may absorb higher amounts of icodextrin and achieve less
      ultrafiltration. The concept of amino acid-based PD fluids is intriguing, but
      pediatric benefits are insufficiently described and cannot replace tube feeding
      in malnourished children. Bicarbonate-based PD fluids better control metabolic
      acidosis and have been recommended in children with acute kidney injury and
      impaired lactate metabolism. This review discusses the scientific evidence and
      potential advantages of PD solutions with an improved biocompatibility profile,
      with a particular focus on pediatric studies.

PMID- 22652711
TI  - Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD): from conception to
      execution of a national peritoneal dialysis reality check.
AB  - Systematic data collection of patients undergoing renal replacement therapy is
      critical to the epidemiological and clinical understanding of the treatment.
      These data may allow more rational use of economic resources and identify
      interventions to improve treatment and decrease the morbidity and mortality of
      these patients. The Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD), an
      observational cohort study of peritoneal dialysis (PD) patients in Brazil, aimed
      to collect monthly demographics, clinical, laboratory and outcome data of PD
      patients treated in 114 dialysis clinics around the country, was started in
      December 2004 and ended in September 2011. BRAZPD has been generating solid and
      important information, which is very useful as a reality check of the PD therapy
      for all Brazilian PD centers.

PMID- 22652712
TI  - Comparing outcomes of hemodialysis and peritoneal dialysis patients: consider the
      pitfalls.
AB  - Patients with end-stage renal disease have a limited life expectancy. It is
      primarily for this reason that there is interest in determining whether one form
      of dialysis therapy provides any survival advantage over another in different
      subgroups of individuals. Randomized controlled clinical trials are the gold
      standard in answering such a question. However, in-center hemodialysis and home
      peritoneal dialysis require profoundly significant but different effects on
      patients' lifestyle and it is not surprising that most patients don't want to
      leave that choice to chance and refuse to participate in such clinical trials.
      Thus, we have to depend upon observational data to compare outcomes with the two
      different dialysis therapies. Yet such studies are not without pitfalls,
      particularly those arising from selection bias, confounding by indication, and
      residual confounding. These pitfalls and potential methods to overcome them are
      discussed in this paper. Despite such adjustments, it is impossible to determine
      if the differences in survival, if any, are a direct result of the dialysis
      modality or from differences in the characteristics of the patients who are
      treated with these therapies. Juxtaposing this limitation with the profound
      impact of dialysis therapies on patients' lives, it is prudent to leave the
      decision of selection of dialysis modality to the patients themselves and
      healthcare providers should offer decision support for individuals attempting to
      make such a selection.

PMID- 22652713
TI  - Hypogonadism in males with chronic kidney disease: another cause of resistance to
      erythropoiesis-stimulating agents?
AB  - Anemia, inflammation, resistance to erythropoiesis-stimulating agents (ESA) and
      hypogonadism (testosterone deficiency) are highly prevalent conditions, which
      heralds poor prognosis, in chronic kidney disease (CKD). It has been speculated
      that testosterone stimulates erythropoiesis via production of hematopoietic
      growth factors and possibly improvement of iron bioavailability. Where as
      inflammation stimulates synthesis of the liver-derived iron regulatory protein
      hepcidin, a recent study suggests that testosterone inhibits hepcidin synthesis,
      thus offering a possible novel mechanism for testosterone-induced erythropoiesis.
      As any agent that lowers hepcidin may be an effective strategy to normalize iron
      homeostasis and overcome renal anemia, testosterone deficiency should be
      considered in this patient group. Indeed, a recent study in males with CKD showed
      that hypogonadism may be an additional cause of anemia and reduced ESA
      responsiveness. Thus, a randomized controlled trial is needed to test the
      possibility that restoration of testosterone levels in hypogonadal CKD males may
      translate into lower prevalence of anemia, better ESA responsiveness and better
      quality of life.

PMID- 22652714
TI  - Getting the right patient on the right renal replacement therapy.
AB  - Adequate selection of the modality of renal replacement therapy (RRT), ideally
      based on well-planned predialysis care, informed decision by the patient and
      timely initiation of dialysis, is essential to optimize the outcome of patients
      with chronic kidney disease. However, there are important practical limitations
      to the success of this process. A major consequence is the underutilization of
      home-based dialysis therapies, including peritoneal dialysis (PD). A wide array
      of medical and social factors have been invoked as contraindications to PD, but
      well-designed studies have shown that most patients (probably >70%) starting
      dialysis are suitable for this technique. PD is feasible and may be preferred by
      a significant proportion of patients in many claimed unfavorable settings. The
      practicing nephrologist should be able to: disclose which are insurmountable
      barriers to PD, clarify the significance of relative contraindications in
      individual cases, and identify favorable and unfavorable settings for home
      dialysis. These abilities will permit quality education, justified advice, well
      targeted informed decision and, predictably, successful selection of the modality
      of RRT. This article provides some clues to approach these issues in three
      different settings: planned start of RRT after predialysis care, unplanned start
      of dialysis and programmed changes of modality during follow-up.

PMID- 22652715
TI  - Doubts on the long-term survival of peritoneal dialysis patients are no longer a
      medical barrier to home dialysis.
AB  - Remarkable differences in the utilization of peritoneal dialysis (PD) versus
      other forms of renal replacement therapy (RRT) exist between different
      continents, countries and even different regions in a given country. Since many
      years a number of medical and nonmedical barriers against home dialysis, notably
      PD have been recognized. One of the reasons for the low utilization of home
      (peritoneal) dialysis is the incomplete presentation of treatment options to the
      patient with ESRD. This review updates some recent data on the long-term survival
      of PD patients in comparison with long-term hemodialysis. Doubts on the long-term
      survival results on PD are still one of the major medical systematic barriers
      preventing the expansion of PD for the treatment of ESRD. These recent survival
      results show that even over a long follow-up time, PD, at least in patients who
      are starting RRT in a planned way, has the same survival as patients starting on
      chronic hemodialysis.

PMID- 22652716
TI  - How to avoid technique failure in peritoneal dialysis patients?
AB  - It is well established that technique failure is one of the main reasons for
      peritoneal dialysis cessation. Early PD failures occur during the first 6 months
      of PD and are mainly related to catheter dysfunction and psychosocial problems.
      Catheter malfunction should be treated by a video-laparoscopic procedure as this
      prolongs the catheter survival. Assisted peritoneal dialysis could help patients
      to cope with peritoneal dialysis. Preservation of residual renal function is of
      importance in peritoneal dialysis patients as it affects both patients and
      technique survival. Failure to obtain a sufficient ultrafiltration volume to
      maintain a euvolemic state without using large amount of hypertonic glucose
      solution can cause peritoneal dialysis failure. New approaches in the use of
      icodextrin to increase ultrafiltration and sodium removal are under
      investigation. A novel modality of prescribing automated peritoneal dialysis
      would improve ultrafiltration in peritoneal dialysis patients.

PMID- 22652717
TI  - Clinical practice guidelines: an important tool in improving dialysis quality.
AB  - Clinical practice guidelines (CPGs) are 'systematically developed statements to
      assist practitioner and patient decisions about appropriate health care for
      specific clinical circumstances'. Ideally they should provide a summary of the
      clinical evidence about a topic, based on relevant systematic reviews, well
      performed metaanalyses or individual sufficiently powered randomized trials. CPGs
      can help physicians and their patients to incorporate the best evidence into
      their individual practice but also inform further research in the field by
      identifying flaws and trends in the literature. Guidelines complement but should
      not replace clinical judgment and are not intended to define a standard of care
      and should thus not be used as outcome performance measures. It should, however,
      be recognized that in nephrology and in dialysis most of the guidelines are based
      on weak evidence and are mostly expert or 'consensus' based. However, there is,
      albeit largely indirect, evidence that adhering to CPGs is associated with
      improvement in dialysis care and even patient outcomes.

PMID- 22652718
TI  - Remote monitoring for continuous peritoneal dialysis.
AB  - Peritoneal dialysis affords patients the luxury of independence and with this an
      improved quality of life. However, patients on peritoneal dialysis still require
      monthly visits with the care team to assess the quality of therapy (volume and
      blood pressure control, solute clearance, attainment of metabolic goals, and
      others). Furthermore, a critical aspect of therapy is that the patient must
      actively monitor their therapy with daily recordings of weight, blood pressure,
      and fluid removal. Remote monitoring of the patient on peritoneal dialysis offers
      the benefits of real-time monitoring and recording of the therapy as well as an
      interactive interface with the care team that may allow both acute 'trouble
      shooting' for problems as well as a means to interact with the patient for their
      monthly evaluation. This remote monitoring allows assurance of patient safety
      through surveillance of critical portions of the treatment as well as the ability
      to monitor compliance with prescribed therapy and automated collection of
      treatment data. Recent advances in telemedicine, telemonitoring, remote network
      access and sensor technologies have made such remote monitoring of peritoneal
      dialysis therapy feasible.

PMID- 22652719
TI  - e-Health: remote health care models in peritoneal dialysis.
AB  - A general review is given on advantages and disadvantages of the various forms of
      e-Health. The sparse available literature on e-Health and peritoneal dialysis is
      discussed. It is concluded that in general e-Health interventions lead to small
      but to moderate positive effects on primary health outcomes, although the
      evidence still is not fully convincing.

PMID- 22652720
TI  - Remote monitoring of peritoneal dialysis in special locations.
AB  - Peritoneal dialysis (PD) as a therapy with all its advantages has not grown as
      would have been expected except in certain pockets, notably in Asia. In our
      opinion, from patient and their family interviews, a perception among prospective
      PD patients of inaccessibility to the referral PD Unit (RPU), usually for
      patients from rural areas in far flung places, inaccessible due to difficult
      terrain or long distances, play a strong role against the choice of PD as their
      modality choice for end-stage renal disease. We decided to address this issue by
      adopting novel initiatives such as easy access to the RPU through usage of
      internet and mobile phones from the patient homes especially in addressing the
      more clinically relevant infectious complications such as peritonitis and exit
      site infections with immediate treatment management responses from the RPU. In
      addition, we found that inherently the rural PD patients had several advantages
      over their urban counterparts and also over their hemodialysis (HD) counterparts
      in many socioeconomic, emotional support and nutritional parameters. We enhanced
      these advantages with an intensive home visit program. This two pronged approach
      has paid dividends in that our rural PD patients do as well, if not better than
      the urban PD and the HD patients, contrary to prevailing international
      experience.

PMID- 22652721
TI  - Dialysis modality choice for the elderly patient with end-stage renal disease.
AB  - The number of elderly patients with stage 5 chronic kidney disease (CKD) is
      growing and leads to challenges in deciding the proper modality of treatment for
      these patients. The majority of these patients will not be candidates for
      transplantation and thus, the choice is between medical management, hemodialysis
      or peritoneal dialysis. Each of these choices had advantages and disadvantages
      and ultimately the decision to select a course of therapy must be individualized
      based upon the benefits and risks of the therapy, patient comorbidities, family
      and community resources and frank discussions regarding goals of care and end-of
      life issues.

PMID- 22652722
TI  - Anemia management in patients on peritoneal dialysis.
AB  - Anemia is a common complication of patients receiving peritoneal dialysis (PD)
      but has been little studied compared to other chronic kidney disease (CKD)
      populations. A number of factors can affect its severity or response to
      erythropoiesis-stimulating agents (ESA). Some, such as iron deficiency, occult
      blood loss, infection, inflammation, oxidative stress, inadequate dialysis dose,
      and hyperparathyroidism are common to all dialysis patients but they may be more
      or less important depending on dialysis modality. The net balance of their
      contribution explains the fact that on average PD patients require less ESA doses
      compared to hemodialysis patients to correct anemia and maintain stable Hb
      levels. As in other CKD patients, low hemoglobin levels have been associated with
      increased mortality in PD patients. Unfortunately, no clinical trials have been
      carried out specifically in this population whether aiming at different Hb
      targets with ESAs may modify patient outcome. Given the lack of a vascular
      access, it is advisable to give PD patients ESA therapy subcutaneously. Long
      acting molecules may be of advantage, especially when the drug is administered at
      the dialysis center.

PMID- 22652723
TI  - Maximizing the erythropoietin response: iron strategies.
AB  - Anemia is a significant cause of morbidity and lowers the quality of life of
      patients suffering from chronic kidney disease (CKD). Iron deficiency is the most
      important cause of erythropoietin (EPO) hyporesponsiveness in CKD. EPO
      administration significantly increases the costs of CKD management. It follows
      that paramount importance must be given to enhancing responsiveness to EPO
      thereby ensuring that the patient derives maximum benefit. Intravenous iron (IVI)
      administration has been used for decades to replenish body iron stores. Multiple
      preparations of Iron are available in the market. However, IVI administration is
      fraught with dangers like adverse drug reactions, susceptibility to infection,
      and, as recently postulated, direct cellular toxicity. Traditional approaches to
      IVI administration have focused on multiple administrations of lower doses for
      fear of adverse reactions. However, recent studies have demonstrated that higher
      doses can be safely administered in a single infusion, thereby reducing
      hospitalization costs and patient inconvenience. Newer preparations of IVI are
      relatively safer, easier to administer and efficacious. Preparations like Iron
      sucrose, ferumoxytol, ferric carboxymaltose and iron isomaltoside do not require
      test doses and allow higher doses to be administered at a time with cost and
      effect benefits.

PMID- 22652724
TI  - Lipid disorders in uremia and dialysis.
AB  - Treatment of cholesterol in people with advanced stage chronic kidney disease
      (CKD) clearly reduces cardiovascular risk; however, it does not significantly
      slow nephropathy progression. Moreover, cholesterol reduction does not reduce
      mortality in people on dialysis. In general, cholesterol reduction is very
      important for reducing cardiovascular risk in people with GFR values >15 ml/min
      who are not on dialysis. There are many reasons for the lack cardiovascular risk
      reduction with cholesterol lowering in dialysis patients including a defective
      HDL and higher than usual oxidation rates of LDL. The reviews some of the
      biochemistry of lipids in uremia and discusses the randomized trial data that
      support these statements and provides greater detail regarding use of statin in
      patients with stages 4 and 5 CKD. Caution should be used in dosing statins in
      stage 3b or higher CKD. Specifically, all statins except for atorvastatin and
      pravastatin need dose reductions due to safety issues. Given the more 'metabolic
      syndrome like' profile of lipids in stage 5 CKD adjunctive methods such as
      fibrates and omega-3 is discussed, however no good data are available in this
      group on outcomes with these agents.

PMID- 22652725
TI  - Statins and lipid-lowering strategies in PD.
AB  - Both traditional and nontraditional cardiovascular risk factors are considered to
      contribute to the high prevalence of cardiovascular disease (CVD) in peritoneal
      dialysis (PD) patients, and CVD is a major cause of both morbidity and mortality
      in this patient population. Among traditional risk factors, lipid disturbances
      are very common in patients with chronic renal failure and PD patients have in
      general, compared to hemodialysis (HD) and nondialyzed patients, an even more
      atherogenic lipid profile. The pathogenesis of the lipid disturbances in PD
      patients is not completely understood, but both the protein loss in the
      dialysate, and the glucose absorption from the dialysate may contribute to these
      alterations. Hydroxymethylglutaryl coenzyme A reductase inhibitors, more commonly
      known as statins, are effective to reduce low density cholesterol levels in PD
      patients and have few side effects. The use of statins is associated with reduced
      mortality in PD patients, but so far no large randomized controlled trial has
      been performed concerning the effects on clinical outcome in PD patients (except
      for the fact that 496 patients in the SHARP trial were treated with PD). In
      addition, except from their lipid lowering effects, statins also have pleiotropic
      effects, independent of their lipid lowering effect, that theoretically have
      beneficial effects on the peritoneal membrane remodeling. Use of alternative
      osmotic agents as well as nutritional interventions has also been reported to
      improve the lipid profilein PD patients.

PMID- 22652726
TI  - Statin therapy is associated with decreased small, dense low-density lipoprotein
      levels in patients undergoing peritoneal dialysis.
AB  - Cardiovascular disease is a major cause of morbidity and mortality among
      hemodialysis (HD) and peritoneal dialysis (PD) patients, and dyslipidemia plays
      an important role in its pathogenesis. In particular, small, dense LDL (sd-LDL)
      particles have been recently highlighted as an emerging cardiovascular risk
      factor. PD patients exhibit a more overtly abnormal lipid profile than HD
      patients, probably due to the metabolic interference of the peritoneal dialysis
      fluid. Statins are the main drugs for the treatment of dyslipidemia and they are
      able to decrease all LDL subclasses levels, but it remains unclear whether they
      can influence the proportion of sd-LDL. Only few studies regarding the effect of
      statins on the proportion of these particles have been performed in HD patients
      and, to our knowledge, no trials have been carried out in PD patients. Therefore,
      we compared the lipid profile and the proportion of sd-LDL in two populations of
      HD and PD patients. Our study suggests that statin therapy may be effective in
      reducing both the absolute amount and the proportion of sd-LDL in patients with a
      more overtly abnormal lipid profile, such as patients undergoing peritoneal
      dialysis. Statins do not seem to be effective in altering sd-LDL levels in
      patients undergoing hemodialysis with other factors that can influence LDL
      subtractions generation, such as hypertension and diabetes mellitus. If and when
      our results prove to be reproducible in large-scale studies, such studies should
      provide new insights into sd-LDL and its actual role in atherogenesis in patients
      undergoing hemodialysis or peritoneal dialysis.

PMID- 22652727
TI  - Phosphate control in peritoneal dialysis.
AB  - Chronic kidney disease (CKD) is characterized by phosphorus retention and, in
      more advanced stages, by high serum phosphorus (P) levels. During the last
      decade, it has been elucidated the central role of P in the pathogenesis of CKD
      mineral bone disorder (CKD-MBD), determining both renal osteodystrophy and
      cardiovascular disease. Unfortunately, at least one third of patients on chronic
      dialysis have high serum P levels, with a consequent higher serum PTH levels,
      commonly associated with vitamin D deficiency, increased vascular calcification
      and the highest ratios of morbidity and mortality. In patients with CKD stage 5
      on dialysis, therapeutic approaches to reduce serum P levels should include
      restriction of dietary phosphate intake, optimal dialysis treatment, and use of P
      binders. In this context, the use of P binders appears to be an essential
      treatment to control P overload in CKD patients. In this review, we analyzed the
      use of calcium-based and calcium-free P binders in peritoneal dialysis patients.

PMID- 22652729
TI  - Calcimimetics in peritoneal dialysis patients.
AB  - Though the prevalence of secondary hyperparathyroidism (SHP) and the related
      mineral metabolism (MM) changes have been reported at almost the same rate in
      peritoneal dialysis (PD) as in hemodialysis (HD) patients, PD patients have a
      higher prevalence of adynamic bone disease (ABD), suggesting that their bone is
      less sensitive for a given level of PTH. Furthermore, the phosphorus control
      seems to be better and vitamin D deficiency is more common in PD patients than in
      HD patients. So, the therapeutic approach to SHP and MM changes in PD patients
      might be different from the one applied to HD patients. Vitamin D metabolites and
      phosphate binders, though effective in controlling SHP of CKD patients, are not
      equally effective in controlling at the same extent calcium and/or phosphorus
      levels. Recently, a new drug (Cinacalcet) has been introduced in the clinical
      practice which significantly increased the chance of obtaining a simultaneous
      control of both PTH and MM parameters. However, only scanty data are present in
      the literature regarding the use of Cinacalcet in PD patients. The few studies
      produced in PD retraced the results obtained in hemodialysis patients, confirming
      that both in the short- and long-term Cinacalcet induced a more pronounced
      reduction of PTH in a larger percentage of patients as compared with standard
      therapy (ST), and this effect was associated with a decrease in both calcium and
      phosphorus concentrations, though the extent of the percentage decrease of
      phosphorus was lower than in HD patients. The safety/tolerability profile was
      again the same as in HD patients, with gastrointestinal symptoms representing the
      more frequently reported side effects. In our experience, given that a severe
      form of SHP is less frequent, the control of phosphate is usually better and
      vitamin D deficiency is more frequent in PD than in HD patients, making the
      former patients more prone to hypo- rather than hypercalcemia, the need for the
      use of the most recent and potent drugs for the control of SHP, including
      Cinacalcet, is usually lower in PD than in HD patients.

PMID- 22652728
TI  - Role of vitamin D receptor activators in peritoneal dialysis.
AB  - Chronic kidney disease (CKD), including patients on peritoneal dialysis (PD), is
      linked to an important increase in mortality risk. Within the new systemic term
      CKD-MBD, alterations in vitamin D metabolism are also included. Many adverse
      events have been associated with vitamin D deficiency or lack of vitamin D
      receptor (VDR) activation both in the general population and CKD patients, and
      these associations seem to be maintained in PD patients. Particularities of PD in
      vitamin D metabolism, calcium balance, low PTH levels and the high prevalence of
      adynamic bone disease are discussed. We also review the associations of clinical
      or survival benefits with vitamin D supplementation, VDR or selective VDR
      activation, although they are low-graded and most of them obtained from HD
      databases. Nevertheless, we think that the combined approach to secondary
      hyperparathyroidism seems also to be appropriate in PD patients, and vitamin D
      (native plus VDR or selective VDR activation) seem an important part of the
      required integral approach. The later may provide additional benefits but
      definitive prove is still lacking.

PMID- 22652730
TI  - Factors affecting loss of residual renal function(s) in dialysis.
AB  - Many physiological processes relate to two aspects of kidney function: (1)
      excretory and secretory (excretion of electrolytes and water, elimination of
      metabolic end products and uremic toxins, regulation of the acid-base status),
      and (2) endocrine functions (regulating bone and mineral metabolism and red blood
      cell production). Decreases in renal functions are known to be associated with
      shortened survival. The exact mechanisms for this are still to be elucidated but
      evidence in the literature suggests mechanisms such as adverse effects of
      accumulation of uremic toxins, fluid overload, inflammation and possibly loss of
      antioxidant functions. Knowledge of factors affecting decrease of residual renal
      function is currently based on observational data only. Possible strategies to
      preserve residual renal function have been suggested but require confirmation in
      adequately powered prospective trials to test their effectiveness.

PMID- 22652732
TI  - Assessment of fluid status in peritoneal dialysis.
AB  - Fluid management is recognized as a basic component of management of patients on
      dialysis. Fluid overload is an important adverse factor in patient outcomes, and
      the negative effects of fluid depletion, including on residual renal function,
      are also increasingly being recognized. The complexities of fluid distribution in
      renal failure need to be understood to inform assessment of hydration. Clinical
      assessment of hydration is insensitive to abnormalities in hydration. BIA is the
      most promising technique for objective assessment of fluid status, but it is
      essential that the underlying principles and limitations are understood, and that
      results from BIA are utilized in conjunction with clinical assessment rather than
      in isolation.

PMID- 22652731
TI  - Prospective safety study of bardoxolone methyl in patients with type 2 diabetes
      mellitus, end-stage renal disease and peritoneal dialysis.
AB  - Patients on peritoneal dialysis experience inflammation associated with advanced
      chronic kidney disease and the therapy itself. An important consequence of the
      inflammation may be acceleration of the rate of decline in residual renal
      function. The decline in residual renal function has been associated with an
      increased mortality for patients in this population. Bardoxolone methyl is a
      synthetic triterpenoid. To date, the effects of bardoxolone methyl on kidney
      function in humans have been studied in patients with type 2 diabetes mellitus. A
      large-scale event-driven study of bardoxolone methyl in patients with type 2
      diabetes mellitus with stage 4 chronic kidney disease is underway. The safety of
      bardoxolone methyl has not been evaluated in patients with more advanced (stage
      5) chronic kidney disease or patients on dialysis. This report describes a
      proposed double blind, prospective evaluation of bardoxolone methyl in patients
      with type 2 diabetes mellitus receiving peritoneal dialysis. In addition to
      assessing the safety of bardoxolone methyl in this population, the study will
      evaluate the effect of bardoxolone methyl on residual renal function over 6
      months as compared to placebo.

PMID- 22652733
TI  - Fluid transport and homeostasis in peritoneal dialysis.
AB  - Ultrafiltration failure is one of the main concerns for patients on long-term
      peritoneal dialysis. According to the three-pore model of peritoneal transport,
      peritoneal water flows via four pathways: ultrasmall pores, small pores, large
      pores and through peritoneal or lymphatic reabsorption. New methods that allow
      clinicians to identify the mechanisms behind disturbances in water transport can
      be applied in clinical practice. Small pore transport and free water transport
      can be estimated after a short 1-hour dwell with a glucose solution, without the
      need for an intraperitoneal volume marker. Until now, peritoneal reabsorption has
      been calculated using indirect and complicated methods. However, a simple,
      standardized method that is useful in clinical practice is needed.
      Ultrafiltration failure may be caused by rapid solute transport, slow solute
      transport, high peritoneal reabsorption and decreased free water transport
      (aquaporin failure). This article briefly discusses the clinical significance of
      disturbances in ultrafiltration, possible improvements in treatment options, and
      how to achieve or maintain fluid homeostasis.

PMID- 22652734
TI  - Bioimpedance and brain natriuretic peptide in peritoneal dialysis patients.
AB  - Assessment of ideal body weight in peritoneal dialysis (PD) patients is important
      for clinical practice. Fluid overload may produce hypertension, reduced arterial
      distensibility, left ventricular hypertrophy. All these are risk factors for
      mortality in PD patients: cardio- and cerebrovascular events are the main causes
      of morbidity and mortality in PD population. Nowadays, a clear and widely
      accepted definition of ideal body weight in PD patients does not exist. Probably
      the ideal body weight is the weight at which the extra cellular volume is normal.
      Many different tools have been used to assess the hydration status in dialysis
      patients. Ultrasonic evaluation of inferior vena cava diameter only assesses
      intravascular volume, and is also influenced by diastolic dysfunction and is thus
      a reflection of preload and not of tissue hydration. Direct measurement of extra
      cellular and total body water by dilution methods is considered as the golden
      standard, but these techniques are laborious and expensive. Parameters, such as
      brain natriuretic peptide (BNP) or NT-proBNP can reflect changes in hydration
      status and may help the nephrologist to estimate it. Natriuretic peptides are
      influenced both by preload and ventricular abnormalities and in patients with
      renal failure accumulation can occur. Bioimpedance is an accurate, reproducible,
      not expensive and not invasive technique that permits a good evaluation of
      hydration status in PD and can drive the nephrologist in his clinical choices.
      Clinical evaluation, strict control of body weight, diuresis, sodium and fluids
      intakes, bioimpedance monitoring and serum levels of natriuretic peptides may all
      together help us to maintain the PD patient euvolemic.

PMID- 22652735
TI  - Role of peritoneal dialysis as a chronic renal replacement therapy in cardiorenal
      patients.
AB  - The cardiorenal syndrome (CRS) is a pathophysiological condition characterized by
      a simultaneous combination of cardiac and renal dysfunction. When diuretic
      resistance occurs, fluid removal by ultrafiltration (UF) is beneficial. However,
      in progressive CRS type II multiple hospitalizations for intravenous therapy or
      extracorporeal UF due to recurrent decompensations have important implications in
      the deterioration of quality of life and in the use of hospital resources.
      Peritoneal daily sustained UF appears to be a good therapeutic tool for the
      chronic ambulatory management of these patients avoiding the risks of a central
      venous access, aggressive volume shifts and the circulatory stress of the
      extracorporeal techniques. Controversies on the results of peritoneal dialysis in
      cardiorenal patients are mostly dependent on therapy skills since individuals
      with heart failure have a narrower window of tolerance, presenting significant
      complications even in presence of small deviations from optimal fluid balance.
      The updated use of volume monitoring tools is recommended. Multifrequency
      bioimpedance allows detailed information on the total body water overload and,
      more importantly on the extracellular/intracellular water distribution. This is
      an instrument that can be longitudinally used to improve the accuracy of clinical
      judgment concerning volume status. Incremental PD with use of icodextrine besides
      the promising role of low sodium solutions and bimodal solutions are therapy
      issues that can improve clinical outcomes of cardio-renal patients under
      peritoneal dialysis, as a home-based continuous therapy.

PMID- 22652736
TI  - Vascular and arterial calcification in peritoneal dialysis patients--state-of-the
      art 2012.
AB  - Vascular calcification is a major challenge to the long-term health of many
      patients with chronic kidney disease, and patients receiving peritoneal dialysis
      therapy are no exception to this. The mechanisms behind vascular calcification
      are complex and diverse. There are several different imaging techniques that can
      be used to interrogate the vasculature in these patients, and the relative merits
      of these as research and screening tools we discuss. There are some recent
      epidemiological studies which throw fresh light on the implications of the
      development or progression of vascular calcification. Finally, an animal model
      experiment is reported which one day may open up the possibility of a successful
      therapeutic intervention.

PMID- 22652737
TI  - Adequacy in peritoneal dialysis.
AB  - Peritoneal dialysis (PD) adequacy is usually estimated by parameters based on the
      kinetics of small solutes as total Kt/V(urea) and total weekly creatinine
      clearance. However, other aspects (blood pressure, anemia, nutrition,
      inflammation, mineral metabolism and prevention of cardiovascular events) and, in
      particular, residual renal function must be taken into account. Although minimal
      levels are well defined, there are no optimal targets to be achieved. Clinical
      assessments are more and more relevant. In addition, fluid and sodium removal
      must be estimated, several studies showing that even in an uric patients adequacy
      can be obtained. Nutrition and inflammation have to be evaluated and their role
      seems to be more important than peritoneal membrane status in patient survival.
      Guidelines and recommendations are available to provide a better follow-up in
      patients on PD.

PMID- 22652738
TI  - Setting up research in peritoneal dialysis.
AB  - Over the past 30 years, peritoneal dialysis (PD) not only developed into a
      valuable treatment modality, but also stimulated basic science research. Here, we
      summarize some of such PD-inspired studies that addressed more general aspects of
      immunology and pathology and helped us to appreciate the complexity of peritoneal
      biology.

PMID- 22652739
TI  - Continuous flow peritoneal dialysis: update 2012.
AB  - Continuous flow peritoneal dialysis (CFPD) is a technique of renal replacement
      therapy (RRT) dating back to the 1950s. Its essential features are a fixed
      intraperitoneal volume and rapid, continuous movement of dialysis solution into
      and out of the peritoneal cavity. Inlet and outlet catheters and a means of
      generating a large volume of sterile dialysate are required. External
      regeneration of dialysate via conventional hemodialysis equipment or sorbent
      technology mitigates the need for large volumes of sterile fluid and makes the
      technique feasible. Clearance depends on peritoneal mass transfer coefficient,
      rate of dialysate flow and efficiency of external regeneration. Studies to date
      all demonstrate small solute clearances 3-8 times greater than conventional
      automated peritoneal dialysis (APD). Catheter design is crucial to the clinical
      success of the technique and will be discussed. Potential applications include
      daily home dialysis, treatment of acute renal failure in the ICU, ultrafiltration
      of ascites, and the wearable artificial kidney.

PMID- 22652740
TI  - Combination therapy: five days PD and one day HD--what are the benefits?
AB  - Other than renal transplantation, the two major treatment options for patients
      with stage V kidney disease are hemodialysis and peritoneal dialysis. Both
      therapies have advantages and disadvantages while there are obvious physical
      differences in the way they are delivered. In clinical practice, one typically
      uses one therapy at a time in patients. However, there are medical and patient
      lifestyle reasons why you may want to use both on a weekly basis. Early clinical
      experience with this approach has been encouraging. With emerging data suggesting
      that more frequent hemodialysis or slower ultrafiltration rates may be beneficial
      for the patient there are now even more compelling reasons to consider this
      approach. This paper reviews the published literature on combined modality
      therapy and suggests reasons why we may want to utilize combination therapy more
      often.

PMID- 22652741
TI  - Peritoneal dialysis access: what's the best approach?
AB  - There are many procedures for placement of an intraabdominal peritoneal catheter
      for peritoneal dialysis. Each one has its own advantages and disadvantages.
      Although the blind technique with a trocar was the initial procedure utilized,
      over the years interventional nephrologists and surgeons have evolved to more
      modern techniques that allow more direct visualization of the peritoneal cavity,
      minimizing complications catheter-related. Novel techniques such as
      peritoneoscopy and laparoscopy appear to be associated with a reduced number of
      exit site infections, lower incidence of peritonitis, decreased risk of leakage
      and improved catheter survival. Since some studies have not seen all these
      benefits associated with these procedures, one recognizes the importance of the
      experience obtained with each procedure in every center and the impossibility of
      generalization.

PMID- 22652742
TI  - Time between peritoneal dialysis catheter insertion and use.
AB  - Successful performance of peritoneal dialysis (PD) is predicated upon the
      presence of a properly functioning catheter. Several techniques are available for
      placing PD catheters among which peritoneoscopic and laparoscopic techniques are
      gaining broader acceptance. Once placed, PD catheters may be used immediately
      with low dialysate volumes and a dry day. Alternatively, utilizing what is now
      referred to as the Moncrief-Popovich technique, they may be embedded
      subcutaneously for later use. Embedding PD catheters following implantation is an
      attractive option with multiple potential advantages. Such advantages may
      encourage wider use of the Moncrief-Popovich technique in PD units Observational
      studies indicate that the duration of catheter embedment between implantation and
      externalization does not appear to affect catheter survival. Larger studies are
      still awaited to further explore the optimum duration of embedment.

PMID- 22652743
TI  - Peritoneal dialysis membrane evaluation in clinical practice.
AB  - A review is given on the various methods to assess the quality of the peritoneum
      as a dialysis membrane. The quality of the peritoneum in patients who are treated
      with chronic peritoneal dialysis (PD) has mainly focused on solute transport.
      Only recently have biomarkers in effluent been considered as useful, but are not
      generally applied. Peritoneal function tests should not be performed only when
      clinical problems are present, but rather on a regular basis, for instance every
      6-12 months. Only in this way can the natural cause become apparent.

PMID- 22652745
TI  - Today's approaches to prevent peritonitis.
AB  - Peritonitis continues to be a significant problem in patients on peritoneal
      dialysis. There is a striking variability of peritonitis rates from one center to
      another. These results suggest that all centers can strive for the low levels of
      peritonitis that are seen at some centers of excellence (0.3 episodes per year at
      risk or lower). Routine monitoring of PD related infections as organism specific
      rates (rather than proportions) is critical to achieving lower rates. Training
      and retraining of PD patients may be key to lowering peritonitis rates,
      particularly from organisms that commonly come from contamination such as
      coagulase-negative staphylococcus (CNS). Rates of CNS peritonitis may be used as
      a hallmark of adequate patient training, with a goal of a CNS peritonitis rate of
      0.03 episodes per year at risk or less. New technology in connectology would be
      helpful to lower peritonitis related to contamination. Protocols to prevent
      peritonitis related to exit site infection include exit site mupirocin or exit
      site gentamicin as part of routine care. A randomized control trial (RCT)
      comparing exit site medi-honey to intranasal mupirocin is nearing completion and
      may prove to be an attractive alternative. Enteric peritonitis may be due to a
      bowel source; there are limited data on approaches to prevention. Procedures such
      as colonoscopy are clearly a risk for peritonitis and prophylaxis is recommended.
      Bowel approaches such as the prescription of a probiotic should be tested in a
      multicenter RCT to see if such approaches may lower enteric peritonitis.
      Hypokalemia is a known risk factor for peritonitis from Enterobacteriacea and
      should be prevented/treated. More research is needed to test various approaches
      to reduce peritonitis. Until more RCTs have been done, best demonstrated
      practices (as outlined in the recent ISPD position paper) should be utilized to
      lower peritonitis rates.

PMID- 22652744
TI  - Bioelectrical impedance analysis in the assessment of hydration status in
      peritoneal dialysis patients.
AB  - OBJECTIVE: Assessment of fluid status in chronic peritoneal dialysis (PD)
      patients is complex. Clinical evaluation based solely on body weight, blood
      pressure, volume of ultrafiltration (UF) and peripheral edema is insufficient. A
      non-invasive test, bioelectrical impedance analysis (BIA) might be of potential
      benefit. AIM: To test whether BIA correlates with other ancillary markers of
      extracellular fluid volume, namely B-type natriuretic peptide (BNP), residual
      renal function (RRF) and UF, and whether BIA provides complementary information
      in categorizing PD patients vis-a-vis hydration status. METHODS: A cross
      sectional study of 61 out-patients on chronic PD. Single-frequency BIA
      measurements of resistance/height were divided into tertiles (lowest: <253
      Omega/m; middle: >253 Omega/m and <316 Omega/m; highest: >316 Omega/m). RESULTS:
      Compared to patients in the highest tertile of BIA (least fluid), patients in the
      lowest tertile (most fluid) had highest BNP, RRF and UF (93.5 vs. 55.0 pg/ml, p =
      0.029; 850 vs. 300 ml/day, p = 0.05; and 1.75 vs. 1.21 l/day, p = 0.023,
      respectively). CONCLUSIONS: BIA tertiles categorized PD patients who differed in
      BNP, RRF and UF in a stepwise pattern, suggesting BIA may better inform hydration
      status, and serve as an additional clinical tool in management of chronic PD
      patients.

PMID- 22652746
TI  - Transplant outcomes and dialysis modality.
AB  - The prevalence of end-stage renal disease continues to rise, and patients are
      treated for increasing periods of time with hemodialysis, peritoneal dialysis,
      and transplantation. Transition from one treatment modality to another is common,
      and the astute clinician should be aware of a wide array of observational data
      regarding the advantages and disadvantages of certain modalities around these
      transition points. In this paper, we explore data that informs lifelong care of
      the ESRD patient. The discussion focuses on the impact of dialysis modality on
      the likelihood of transplantation, and then moves to short-term and long-term
      outcomes after transplantation. Large observational studies indicate that
      peritoneal dialysis patients may experience increased rates of graft thrombosis
      and early (3-month) graft failure. Importantly, however, compared to their HD
      counterparts PD patients enjoy advantages in shorter time to transplantation,
      decreased rates of delayed graft function (DGF), and enhanced long-term
      transplant survival.

PMID- 22652747
TI  - Neutrophil gelatinase-associated lipocalin in the early diagnosis of peritonitis:
      the case of neutrophil gelatinase-associated lipocalin.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL), a protein involved in iron
      handling, has been recognized as a marker of inflammation. In this regard, serum
      and urine NGAL levels have proven a useful diagnostic tool for acute kidney
      injury. Bacterial peritonitis is an all too common complication of peritoneal
      dialysis (PD) and while diagnosis in most cases is routine, there are times when
      patients present with typical symptoms but do not have an elevated PD effluent
      white blood cell count. Furthermore, patients may present with an elevated PD
      fluid white count, a cloudy effluent and no evidence of active infection. In
      these cases, a discriminating role for peritoneal fluid NGAL would be useful to
      distinguish bacterial and nonbacterial PD fluid infection. A small case control
      study was performed which demonstrated a very high sensitivity and specificity
      for peritoneal fluid NGAL. These preliminary data show that peritoneal fluid NGAL
      may be a useful tool for the early and accurate diagnosis of peritonitis.

PMID- 22652748
TI  - Prognostic factors for peritonitis outcome.
AB  - Despite advances in treatment and prevention, peritonitis remains a major problem
      in peritoneal dialysis (PD) patients with often technique failure as a
      consequence. The last decades the focus of PD peritonitis has changed from
      lowering peritonitis incidence to improvement of peritonitis outcome. Prognostic
      factors for peritonitis outcome can influence decision making during the
      treatment of peritonitis, for example to take out the PD catheter early in the
      time course of peritonitis and prevent further damage to the peritoneal membrane.
      In this paper, we give a review of the literature about prognostic factors for
      peritonitis outcome. In most studies, age, gender, diabetes, time on PD, a
      precursor of calcitonin:procalcitonin, IL-6 and albumin did not show a
      significant effect on peritonitis outcome. The following factors have been
      associated with poor outcome of peritonitis: Gram-negative organisms,
      Mycobacterium species, fungal peritonitis, polymicrobial peritonitis, concurrent
      exit site or tunnel infection, Caucasian race, low residual GFR, persistently
      elevated peritoneal dialysate white cell count, CRP, and low levels of slCAM-1
      and hyaluronan at the end of peritonitis treatment. In fungal peritonitis,
      abdominal pain, bowel obstruction, the catheter remaining in situ and
      Candidaparapsilosis are factors associated with higher mortality rate and a
      greater risk of technique failure. Recent antibiotic therapy and peritonitis are
      associated with poor treatment response in culture-negative peritonitis.
      Recurrent peritonitis episodes have a poor therapeutic response and high
      mortality and have a worse prognosis than relapsing ones. Older age, long PD
      duration and continuous elevated serum CRP levels are predictors of adverse
      outcomes in PD patients after peritonitis-related catheter removal. Peritonitis
      remains a serious complication of PD with marked morbidity. It is a common cause
      of technique failure. The rate of PD-related peritonitis has decreased over the
      last decades due to advances in treatment and prevention. Nowadays, the focus
      moved from lowering peritonitis incidence towards improving peritonitis outcome.
      It is useful to have prognostic factors for peritonitis outcome, because they can
      influence decision-making during the treatment of peritonitis, for example to
      take out the PD catheter early in the time course of peritonitis and prevent
      further damage to the peritoneal membrane. In the last decades, many publications
      appeared about prognostic factors for peritonitis outcome. This article
      summarizes those prognostic factors, based on an extensive review of the
      literature.

PMID- 22652749
TI  - Improving the care of diabetic patients on peritoneal dialysis.
AB  - An overwhelming majority of patients on dialysis reach end-stage renal disease
      (ESRD) secondary to diabetes mellitus (DM). Although renal transplantation offers
      the best option for these patients, shortage of available kidneys becomes a major
      impediment. Besides hemodialysis (HD), peritoneal dialysis (PD) is also a
      commonly offered dialysis modality to these patients. However, PD in diabetics
      poses unique challenges. A constant exposure to glucose in the dialysate may
      further worsen the internal milieu of hyperglycemic diabetic individuals. A
      number of factors may help improve outcomes in such patients. Protection of the
      peritoneal membrane and residual renal function (RRF) are extremely important in
      this regard. Close monitoring of blood glucose levels and prompt management of
      peritoneal and exit site infections can prevent long term complications. This
      brief review addresses some important measures that can help improve outcomes of
      such patients on PD.

PMID- 22652750
TI  - How to select among dialysis options.
AB  - End-stage renal disease is an almost unique disease area in which patients not
      only choose their treatment modality but can also change their mind and their
      treatment as time goes by. The way that information about treatment options is
      presented to patients is critical in influencing how they process this
      information, and it is possible to present information to patients in different
      ways so that patients can make better decisions about the treatment they receive.
      It is important to recognize that simply giving more information to patients does
      not necessarily improve their ability to make decisions. Instead, a series of
      simple principles should be used when giving information to help patients to
      choose between dialysis options, and it is possible to put this together into
      'patient decision aid' which will reduce bias and increase the likelihood of a
      patient choosing the treatment which is right for them. If a patient does do
      this, it is more likely that they will comply with the treatment better, tolerate
      complications of the treatment better, and experience better outcomes.

PMID- 22652751
TI  - Apportioning variability of polycyclic aromatic hydrocarbons (PAHs) and
      chlordanes in indoor and outdoor environments.
AB  - Measurements of semi-volatile organic compounds (SVOCs) in air are subject to
      substantial variability and uncertainty. This study apportions total variance of
      polycyclic aromatic hydrocarbons (PAHs) and chlordanes to variability and
      uncertainty components. Concentrations of PAHs and chlordanes were measured
      inside and outside of 116 residences in three large cities in the U.S. during
      1999-2000. Total variance was apportioned to between-city, between-tract, between
      residence, and seasonal variation, as well as measurement uncertainty using
      variance component analysis and log-transformed data for frequently detected
      compounds. Outdoors, seasonal variation was the greatest portion (44-67%) of
      total variance, and city effects were significant (19-24%). Indoors, seasonality
      dominated variability of PAH measurements (>50%). Gas-phase PAHs varied more
      within city than between cities; particulate-phase PAHs varied significantly
      between cities but were largely homogeneous within cities. Gas-phase chlordanes
      showed larger intra-urban variation (63%) than seasonal variation (18%).
      Measurement uncertainty was generally below 10% with a few exceptions occurring
      at very low concentrations. Results indicate a need to collect multiple-season
      samples to account for the large temporal variation between seasons. Samples from
      centrally located monitoring stations could be representative of ambient SVOCs.
      Variance component analysis is useful to weigh influential factors in SVOC
      concentrations, identify and apportion sources, evaluate method performance, and
      design effective monitoring programs.

PMID- 22652753
TI  - Electrodeposition of gold thin films with controlled morphologies and their
      applications in electrocatalysis and SERS.
AB  - Here, an easy and effective electrochemical route towards the synthesis of gold
      thin films with well-controlled roughness, morphology and crystallographic
      orientation is reported. To control these different factors, the applied
      potential during deposition played a major role. A tentative nucleation and
      growth mechanism is demonstrated by means of electrochemical characterizations
      and a formation mechanism is proposed. Interestingly, the differences in geometry
      and orientation of the different gold deposits have shown a clear correlation
      with the electrocatalytical activity in the case of oxygen sensing. In addition,
      not only the electrocatalytical activity but also the surface-enhanced Raman
      scattering of the gold deposits have been found to depend both on the roughness
      and on the size of the surface nanostructures, allowing a fine tuning by
      controlling these two parameters during deposition.

PMID- 22652752
TI  - Autophagy is active in normal colon mucosa.
AB  - Recently, autophagy has been found to be strongly activated in colon cancer
      cells, but few studies have addressed the normal colon mucosa. The aim of this
      study was to characterize autophagy in normal human intestinal cells. We used the
      expression of LC3-II and BECN1 as well as SQSTM1 as markers of autophagy
      activity. Using the normal human intestinal epithelial crypt (HIEC) cell
      experimental model, we found that autophagy was much more active in
      undifferentiated cells than in differentiated cells. In the normal adult colonic
      mucosa, BECN1 was found in the proliferative epithelial cells of the lower part
      of the gland while SQSTM1 was predominantly found in the differentiated cells of
      the upper part of the gland and surface epithelium. Interestingly, the weak
      punctate pattern of SQSTM1 expression in the lower gland colocalized with BECN1
      labeled autophagosomes. The usefulness of SQSTM1 as an active autophagy marker
      was confirmed in colon cancer specimens at the protein and transcript levels. In
      conclusion, our results show that autophagy is active in the colonic gland and is
      associated with the intestinal proliferative/undifferentiated and progenitor cell
      populations.

PMID- 22652755
TI  - Leukemia-associated antigens and their relevance to the immunotherapy of acute
      myeloid leukemia.
AB  - The graft-versus-leukemia effect of allogeneic hematopoietic stem cell
      transplantation (HSCT) has shown that the immune system is capable of eradicating
      acute myeloid leukemia (AML). This knowledge, along with the identification of
      the target antigens against which antileukemia immune responses are directed, has
      provided a strong impetus for the development of antigen-targeted immunotherapy
      of AML. The success of any antigen-specific immunotherapeutic strategy depends
      critically on the choice of target antigen. Ideal molecules for immune targeting
      in AML are those that are: (1) leukemia-specific; (2) expressed in most leukemic
      blasts including leukemic stem cells; (3) important for the leukemic phenotype;
      (4) immunogenic; and (5) clinically effective. In this review, we provide a
      comprehensive overview on AML-related tumor antigens and assess their
      applicability for immunotherapy against the five criteria outlined above. In this
      way, we aim to facilitate the selection of appropriate target antigens, a task
      that has become increasingly challenging given the large number of antigens
      identified and the rapid pace at which new targets are being discovered. The
      information provided in this review is intended to guide the rational design of
      future antigen-specific immunotherapy trials, which will hopefully lead to new
      antileukemia therapies with more selectivity and higher efficacy.

PMID- 22652759
TI  - Purification, characterization and structural determination of chitinases
      produced by Moniliophthora perniciosa.
AB  - The enzyme chitinase from Moniliophthora perniciosa the causative agent of the
      witches' broom disease in Theobroma cacao, was partially purified with ammonium
      sulfate and filtration by Sephacryl S-200 using sodium phosphate as an extraction
      buffer. Response surface methodology (RSM) was used to determine the optimum pH
      and temperature conditions. Four different isoenzymes were obtained: ChitMp I,
      ChitMp II, ChitMp III and ChitMp IV. ChitMp I had an optimum temperature at 44
      73oC and an optimum pH at 7.0-8.4. ChitMp II had an optimum temperature at 45
      73oC and an optimum pH at 7.0-8.4. ChitMp III had an optimum temperature at 54
      67oC and an optimum pH at 7.3-8.8. ChitMp IV had an optimum temperature at 60oC
      and an optimum pH at 7.0. For the computational biology, the primary sequence was
      determined in silico from the database of the Genome/Proteome Project of M.
      perniciosa, yielding a sequence with 564 bp and 188 amino acids that was used for
      the three-dimensional design in a comparative modeling methodology. The generated
      models were submitted to validation using Procheck 3.0 and ANOLEA. The model
      proposed for the chitinase was subjected to a dynamic analysis over a 1 ns
      interval, resulting in a model with 91.7% of the residues occupying favorable
      places on the Ramachandran plot and an RMS of 2.68.

PMID- 22652760
TI  - Production, extraction and characterization of exopolysaccharides produced by the
      native Leuconostoc pseudomesenteroides R2 strain.
AB  - The genus Leuconostoc belongs to a group of lactic acid bacteria usually isolated
      from fermented vegetables, which includes species involved in the production of
      exopolysaccharides (EPS). These biopolymers possess considerable commercial
      potential. Because of the wide variety of industrial applications of EPS, this
      study aimed to produce and characterize the native exopolysaccharide strain
      Leuconostoc pseudomesenteroides R2, which was isolated from cabbage collected in
      a semi-arid region of Bahia. We employed the following conditions for the
      production of EPS: 10.7% sucrose, pH 8.2, without agitation and incubation at
      28oC for 30 hours. The fermentation broth was treated with ethanol and generated
      two types of polysaccharide substances (EPS I and EPS II). The identification of
      EPS I and EPS II was conducted using FT-IR, (1)H, (13)C and DEPT-135 NMR spectra.
      The two substances were identified as linear dextran alpha polysaccharides (1 ->
      6) which indicated different characteristics with respect to thermal analysis and
      density of free packaging, viscosity and time of solubilization. Both dextrans
      are of low density, possess high thermal stability and exhibited the behavior
      characteristic of pseudoplastic polymers.

PMID- 22652762
TI  - Reviewing reasons for the decreased CSF Abeta42 concentration in Alzheimer
      disease.
AB  - Cerebrospinal fluid (CSF) amyloid beta42 (Abeta42) concentrations are decreased
      in patients with Alzheimer disease (AD). Consequently, low Abeta42 is considered
      a positive biomarker for AD. Surprisingly, the mechanisms that underlie the
      decrease in CSF Abeta42 remain speculative. Better understanding of this
      biomarker is an essential step to unravel AD pathophysiology and to develop and
      evaluate treatment. Therefore, we systematically examined the possible reasons
      for the decreased CSF Abeta42 concentration in AD. Under normal conditions,
      Abeta42 can be degraded by proteases, taken up by microglia, or cleared from the
      brain interstitial fluid across the blood brain barrier. Alternatively, it can be
      transported to the CSF and be cleared from there. Aggregation of Abeta42 appears
      the most likely cause for the decreased CSF Abeta42 concentration in AD: the
      aggregated state inhibits Abeta42 from being transported from the ISF to the CSF.
      Evidence for other possibilities such as a decreased production of Abeta42, an
      increased proteolytic breakdown or microglial uptake of Abeta42, or an increased
      clearance of Abeta42 to the blood, is - at best - scarce or even absent.

PMID- 22652763
TI  - Phytoalexins in cancer prevention.
AB  - Plant phytoalexins are a class of low molecular weight compounds that accumulate
      in response to biotic and abiotic elicitors such as pathogens, wounding,
      freezing, UV light, and exposure to agricultural chemicals.  Phytoalexins have
      been identified in at least 75 plants including cruciferous vegetables, soybean,
      garlic, tomato, rice, beans, and potatoes suggesting plants may be a rich source
      of cancer-fighting compounds. Preclinical evidence suggests these compounds
      possess anticancer properties including an inhibition of microbial activity, cell
      proliferation, invasion and metastasis, hormonal stimulation, and stimulatory
      effects on expression of metabolizing enzymes. This review highlights the
      plausible molecular mechanisms through which phytoalexins regulate biological
      processes that can impinge cancer development.  Targets of phytoalexins include
      signal transduction pathways, transcription factors, cell cycle checkpoints,
      intrinsic and extrinsic apoptotic pathways, cell invasion and matrix
      metalloproteinase, nuclear receptors, and the phase II detoxification pathway. 
      Additional research should address physiological relevant dietary concentrations,
      combinations of phytoalexins and interactions with other dietary compounds,
      duration of exposure, and tissue specificity as variables that influence the
      effectiveness of phytoalexins on normal and cancerous processes.

PMID- 22652764
TI  - Src-mediated regulation of E-cadherin and EMT in pancreatic cancer.
AB  - The Src family of non receptor tyrosine kinases are integrators of divergent
      signal transduction pathways which regulate numerous cellular processes,
      including tumorigenicity and angiogenesis. In pancreatic adenocarcinoma, c-Src
      (Src) is frequently activated and results in increased tumor progression,
      invasion and metastasis. Dysfunction of the E-cadherin-mediated cell adhesion
      system plays an important role in tumor progression to invasive, metastatic
      carcinoma. Src has been shown to play a role in E-cadherin regulation and
      epithelial to mesenchymal transition (EMT). Increased Src activity promotes EMT
      while Src inhibition suppresses this process. Recent studies have focused on Src
      dependent regulation of E-cadherin and other tumor progression-related events
      such as EMT with the development of metastasis. Src has also been shown to be
      involved in chemoresistance of PDAC cells by promoting EMT. Although the
      molecular events associated with Src-dependent regulation of E-cadherin are
      becoming better defined, the cellular processes that trigger the onset of EMT
      remain unclear. Here we highlight recent work that advances our understanding of
      Src signaling as it relates to E-cadherin associated regulation and EMT in PDAC.

PMID- 22652766
TI  - Molecular pharmacology of histamine H4 receptors.
AB  - The histamine H4 receptor (H4R) is the youngest member of the histamine receptor
      family. Based on its predominant expression pattern in hematopoietic cells, the
      H4R is considered to be an interesting drug target for inflammatory disorders
      such as allergy and asthma. Since the identification and cloning of the H4R in
      2000, drug discovery programs boosted the development of various H4R (specific)
      ligands. Differences between H4R orthologs in combination with available three
      dimensional G protein-coupled receptor (GPCR) models have guided site-directed
      mutagenesis studies to gain insight in ligand binding and receptor activation. In
      addition, ongoing characterization of H4R-mediated signaling in transfected and
      native cells contributes to further unravel the (patho-) physiological functions
      of H4Rs.

PMID- 22652767
TI  - JAK and Src tyrosine kinase signaling in asthma.
AB  - Tyrosine kinases play a critical role in transducing intracellular signals from
      the receptors. Many receptors do not have intrinsic tyrosine kinase activity, so
      they rely on cytosolic and/or membrane-associated tyrosine kinases for initial
      signal generation.  The Src and JAK family kinases are frequently associated with
      receptors and generate the initial cytosolic signals.  These signals are then
      transduced to other compartments of the cytosol and to the nucleus to elicit a
      specific cellular response.  In this review we focus on these two families of
      tyrosine kinases and review their involvement in activation of cells that are
      involved in the pathogenesis of asthma.  A Th2-type immune response dominates the
      processes that lead to the phenotype of asthma.  For this reason we give special
      attention to the tyrosine kinases that are involved in a Th2 response.  Further
      we examine the involvement of tyrosine kinases in activation of mast cells,
      eosinophils and other cells.

PMID- 22652761
TI  - Protein-mediated enamel mineralization.
AB  - Enamel is a hard nanocomposite bioceramic with significant resilience that
      protects the mammalian tooth from external physical and chemical damages. The
      remarkable mechanical properties of enamel are associated with its hierarchical
      structural organization and its thorough connection with underlying dentin. This
      dynamic mineralizing system offers scientists a wealth of information that allows
      the study of basic principels of organic matrix-mediated biomineralization and
      can potentially be utilized in the fields of material science and engineering for
      development and design of biomimetic materials. This chapter will provide a brief
      overview of enamel hierarchical structure and properties and the process and
      stages of amelogenesis. Particular emphasis is given to current knowledge of
      extracellular matrix protein and proteinases, and the structural chemistry of the
      matrix components and their putative functions. The chapter will conclude by
      discussing the potential of enamel for regrowth.

PMID- 22652768
TI  - Mechanistic insight into Type I restriction endonucleases.
AB  - Restriction and modification are two opposing activities that are used to protect
      bacteria from cellular invasion by DNA (e.g. bacteriophage infection). 
      Restriction activity involves cleavage of the DNA; while modification activity is
      the mechanism used to "mark" host DNA and involves DNA methylation. The study of
      Type I restriction enzymes has often been seen as an esoteric exercise and this
      reflects some of their more unusual properties - non-stoichiometric (non
      catalytic) cleavage of the DNA substrate, random cleavage of DNA, a massive
      ATPase activity, and the ability to both cleave DNA and methylate DNA.  Yet these
      enzymes have been found in many bacteria and are very efficient as a means of
      protecting bacteria against bacteriophage infection, indicating they are
      successful enzymes. In this review, we summarise recent work on the mechanisms of
      action, describe switching of function and review their mechanism of action.  We
      also discuss structural rearrangements and cellular localisation, which provide
      powerful mechanisms for controlling the enzyme activity.  Finally, we speculate
      as to their involvement in recombination and discuss their relationship to
      helicase enzymes.

PMID- 22652765
TI  - Superfamily 2 helicases.
AB  - Superfamily 2 helicases are involved in all aspects of RNA metabolism, and many
      steps in DNA metabolism.  This review focuses on the basic mechanistic,
      structural and biological properties of each of the families of helicases within
      superfamily 2.  There are ten separate families of helicases within superfamily
      2, each playing specific roles in nucleic acid metabolism.  The mechanisms of
      action are diverse, as well as the effect on the nucleic acid.  Some families
      translocate on single-stranded nucleic acid and unwind duplexes, some unwind
      double-stranded nucleic acids without translocation, and some translocate on
      double-stranded or single-stranded nucleic acids without unwinding.

PMID- 22652769
TI  - Ubiquitin and its binding domains.
AB  - Post-translational modification by ubiquitin (ubiquitination, ubiquitylation,
      ubiquitinylation) is used as a robust signaling mechanism in a variety of
      processes that are essential for cell homeostasis. Its signaling specificity is
      conferred by the inherent dynamics of ubiquitin, the multivalency of ubiquitin
      chains, and its subcellular context, often defined by ubiquitin receptors and the
      substrate. Greater than 150 ubiquitin receptors have been found and their
      ubiquitin-binding domains (UBDs) are structurally diverse and include alpha
      helical motifs, zinc fingers (ZnF), pleckstrin-homology (PH) domains, ubiquitin
      conjugating (Ubc)-related structures and src homology 3 (SH3) domains. New UBD
      structural motifs continue to be identified expanding the ubiquitin-signaling map
      to proteins and structural families not previously associated with ubiquitin
      trafficking. In this manuscript, we highlight several ubiquitin receptors from
      the multiple UBD folds with a focus on the structural characteristics of their
      interaction with ubiquitin.

PMID- 22652770
TI  - Enabling  techniques for in vitro studies on mammalian spinal locomotor
      mechanisms.
AB  - The neonatal rodent spinal cord maintained in vitro is a powerful model system to
      understand the central properties of spinal circuits generating mammalian
      locomotion. We describe three enabling approaches that incorporate afferent input
      and attached hindlimbs. (i) Sacral dorsal column stimulation recruits and
      strengthens ongoing locomotor-like activity, and implementation of a closed
      positive-feedback paradigm is shown to support its stimulation as an untapped
      therapeutic site for locomotor modulation. (ii) The spinal cord hindlimbs
      restrained preparation allows suction electrode electromyographic recordings from
      many muscles. Inducible complex motor patterns resemble natural locomotion, and
      insights into circuit organization are demonstrated during spontaneous motor
      burst 'deletions', or following sensory stimuli such as tail and paw pinch. (iii)
      The spinal cord hindlimbs-pendant preparation produces unrestrained hindlimb
      stepping. It incorporates mechanical limb perturbations, kinematic analyses,
      ground reaction force monitoring, and the use of treadmills to study spinal
      circuit operation with movement-related patterns of sensory feedback while
      providing for stable whole-cell recordings from spinal neurons. Such techniques
      promise to provide important additional insights into locomotor circuit
      organization.

PMID- 22652771
TI  - Telomere dysfunction and genome instability.
AB  - The nucleoprotein complexes that cap the very ends of the eukaryotic chromosomes,
      named telomeres, are indispensable for cell viability. Telomeric DNA shortens in
      each cell division until it cannot exert end-protective functions in human
      somatic cells. Additionally, several proteins have been described to play a key
      role in telomere homeostasis preventing chromosome extremities to be recognized
      as double-stranded breaks (DSBs). When telomeres become dysfunctional, either
      through excessive shortening or due to defects in the proteins that form its
      structure, they trigger p53/pRb pathways what limits proliferative lifespan.
      Impairment of telomere function together with a compromised senescence/apoptosis
      response leads to chromosome instability. Fusions between dysfunctional telomeres
      or even between dysfunctional telomeres and DSBs can initiate breakage-fusion
      bridge (BFB) cycles. Initially, telomere fusions were proposed to cause only
      structural abnormalities. Nevertheless, changes in chromosome number have also
      emerged as a possible consequence of alterations in end capping. Here we review
      the main aspects of telomeres and telomere-based chromosome instability,
      highlighting why they have been proposed as a driving force for tumourigenesis.

PMID- 22652772
TI  - The Fbw7 and betaTRCP E3 ubiquitin ligases and their roles in tumorigenesis.
AB  - The Ubiquitin Proteasome System (UPS) is a major regulator of protein abundance
      in the cell.  The UPS influences the functions of multiple biological processes
      by targeting key regulators for destruction. E3 ubiquitin ligases are a vital
      component of the UPS machinery, working with E1 and E2 enzymes to bind substrates
      and facilitate the transfer of ubiquitin molecules onto the target protein.  This
      poly-ubiquitination, in turn, directs the modified proteins for proteolysis by
      the 26S proteasome.  As the UPS regulates the degradation of multiple oncogenes
      and tumor suppressors, the dysregulation of this pathway is known to promote
      various diseases including cancer.  While E1 and E2 enzymes have only been
      minimally linked to cancer development, burgeoning amounts of evidence have
      implicated loss or gain of E3 function as a key factor in cancer initiation and
      progression. This review will examine the literature on two SCF-type E3 ligases,
      SCFFbw7 and SCFbeta-TRCP.  In particular, we will highlight novel substrates
      recently identified for these two E3 ligases, and further discuss how UPS
      regulation of these targets may promote carcinogenesis.

PMID- 22652774
TI  - Regulatory roles for L-arginine in reducing white adipose tissue.
AB  - As the nitrogenous precursor of nitric oxide, L-arginine regulates multiple
      metabolic pathways involved in the metabolism of fatty acids, glucose, amino
      acids, and proteins through cell signaling and gene expression.  Specifically,
      arginine stimulates lipolysis and the expression of key genes responsible for
      activation of fatty acid oxidation to CO2 and water. The underlying mechanisms
      involve increases in the expression of peroxisome proliferator-activated receptor
      gamma coactivator-1 alpha (PGC-1 alpha), mitochondrial biogenesis, and the growth
      of brown adipose tissue growth. Furthermore, arginine regulates adipocyte-muscle
      crosstalk and energy partitioning via the secretion of cytokines and hormones. In
      addition, arginine enhances AMP-activated protein kinase (AMPK) expression and
      activity, thereby modulating lipid metabolism and energy balance toward the loss
      of triacylglycerols. Growing evidence shows that dietary supplementation with
      arginine effectively reduces white adipose tissue in Zucker diabetic fatty rats,
      diet-induced obese rats, growing-finishing pigs, and obese patients with type II
      diabetes. Thus, arginine can be used to prevent and treat adiposity and the
      associated metabolic syndrome.

PMID- 22652775
TI  - Cobalt chloride improves angiogenic potential of CD133+ cells.
AB  - Umbilical cord blood-derived CD133+ cells exhibit the ability to differentiate
      into endothelial cells and induce new blood vessel growth. Hypoxia-inducible
      factor-1 (HIF-1), a regulator of hypoxia or the hypoxia-mimetic agent response,
      actives the SDF-1/CXCR4 signaling pathway and thus plays an important role in
      angiogenesis in-vivo. In this study we aim to investigate whether CD133+ cells
      enhance angiogenic ability through hypoxia or CoCl2 in vitro. The CD133+ cells
      were cultured in normoxia (20 Percent O2), hypoxia (10 Percent O2, 3 Percent O2),
      or in various concentrations of CoCl2 (50 microM/L, 100 microM/L, 200 microM/L)
      and subjected to in vitro flow cytometric analysis, tubule formation, as well as
      migration and proliferation assays. The results demonstrate that both
      environmental hypoxia and CoCl2 induced hypoxia result in significantly increased
      CD133+ cell migration, proliferation, and tubule-like structure formation
      compared with normoxia culture conditions. The HIF-1a, SDF-1, and VEGF protein
      and gene expression level in conditions of hypoxia is higher than that found in
      normaxia conditions. Collectively, these data suggest that angiogenic potential
      of CD133+ cells is influenced by hypoxia or a hypoxia mimetic agent in vitro.

PMID- 22652776
TI  - Dietary approach in the prevention and treatment of NAFLD.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a rapidly emerging chronic liver
      disorder and will increasingly be a critical global health problem. Diet is an
      important pathogenic factor of NAFLD and it is well documented that the increased
      prevalence of NAFLD during the last decades was associated with deep modification
      of dietary habits, especially increased  intakes of fats and simple
      carbohydrates. As the disease stems from excess calorie intake and lack of
      physical activity, the correction of unhealthy lifestyles is the basis  of any
      prevention and treatment strategy while drugs should remain a second-line of
      treatment.  NAFLD patients should receive counselling for a low carbohydrate and
      low saturated fat diet, avoidance of fructose-enriched soft drinks and increased
      consumption of fruits and vegetables. The use of functional foods in NAFLD has
      been poorly studied and up to day only few reports are encouraging and incite the
      promotion of functional food approach  on NAFLD prevention on the basis of food
      and nutritional genomics.

PMID- 22652777
TI  - Geldanamycin and its derivatives as Hsp90 inhibitors.
AB  - The Hsp90 molecule, one of the most abundant heat shock proteins in mammalian
      cells, maintains homeostasis and prevents stress-induced cellular damage. Hsp90
      is expressed under normal conditions at a level of about 1-2 Percent of total
      proteins, while its expression increases 2-10 fold in cancer cells. The two main
      constitutively expressed isoforms of Hsp90 are known as Hsp90-alpha and Hsp90
      beta, and their upregulation is associated with tumor progression, invasion and
      formation of metastases, as well as development of drug resistance. The Hsp90 is
      a key target for many newly established, potent anticancer agents containing
      Hsp90 N-terminal ATP binding inhibitors, such as geldanamycin, and its analogues
      17AAG and 17DMAG. The therapeutic usage of geldanamycin has been limited due to
      its poor water solubility and severe hepatotoxicity. Therefore, its analogues,
      including 17AAG, 17DMAG, Tanespimycin and Retaspimycin hydrochloride, with
      improved pharmacokinetic profiles, have been developed.

PMID- 22652773
TI  - Autosomal recessive nonsyndromic deafness genes: a review.
AB  - More than 50 Percent of prelingual hearing loss is genetic in origin, and of
      these up to 93 Percent are monogenic autosomal recessive traits. Some forms of
      genetic deafness can be recognized by their associated syndromic features, but in
      most cases, hearing loss is the only finding and is referred to as nonsyndromic
      deafness. To date, more than 700 different mutations have been identified in one
      of 42 genes in individuals with autosomal recessive nonsyndromic hearing loss
      (ARNSHL). Reported mutations in GJB2, encoding connexin 26, makes this gene the
      most common cause of hearing loss in many populations. Other relatively common
      deafness genes include SLC26A4, MYO15A, OTOF, TMC1, CDH23, and TMPRSS3. In this
      report we summarize genes and mutations reported in families with ARNSHL. Founder
      effects were demonstrated for some recurrent mutations but the most significant
      findings are the extreme locus and allelic heterogeneity and different spectrum
      of genes and mutations in each population.

PMID- 22652778
TI  - Neutrophils in acute lung injury.
AB  - Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is
      characterised by lung oedema due to increased permeability of the alveolar
      capillary barrier and subsequent impairment of arterial oxygenation. Lung oedema
      and endothelial and epithelial injury are accompanied by an influx of neutrophils
      into the interstitium and alveolar space. Hence, the activation and recruitment
      of polymorphonuclear neutrophils (PMNs) are thought to play key roles in the
      progression of ALI/ARDS. Neutrophils, which have anti-microbial activity, are the
      first cells to be recruited to the site of inflammation. This review focuses on
      the mechanisms of neutrophil activity in patients with ALIs with respect to
      attachment, recruitment, adhesion, migration, activation, release of damage
      mediators, and apoptosis via PMNs.

PMID- 22652779
TI  - Th17 related cytokines in acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is the most common hematological malignancy in
      adults, characterized by distorted proliferation and development of myeloid cells
      and their precursors in blood and bone marrow. Impressive biologic advances have
      increased our understanding of leukemogenesis, however, little is known about the
      pathogenic events which lead to the initiation and progression of AML. T helper
      type 17 (Th17) cells are a unique subset of CD4+ T cells. They play important
      roles in the pathogenesis of many diseases, including inflammatory diseases,
      autoimmune diseases, and cancers. A range of cytokines, such as interleukin (IL)
      23, transforming growth factor-beta (TGF-beta), IL-1beta, IL-6, IL-17, IL-22, and
      IL-21, have been shown related to Th17 cells. Some researchers have reported that
      the levels of Th17 and its related cytokines were different between normal cells
      and malignant AML cells, suggesting that Th17 might be involved in AML
      pathogenesis. In this review, we summarize current progress in the mechanisms of
      Th17 related cytokines in AML pathogenesis.

PMID- 22652780
TI  - PDCD10 interacts with STK25 to accelerate cell apoptosis under oxidative stress.
AB  - An apoptosis-related protein, cerebral cavernous malformation 3 (CCM3 or PDCD10),
      has recently been implicated in mutations associated with cerebral cavernous
      malformation. Herein, we show that PDCD10 interacts with serine/threonine kinase
      25 (STK25), an oxidant stress response kinase related to sterile-20 (Ste20) that
      is activated by oxidative stress and induces apoptotic cell death. Functional
      investigations indicate that PDCD10 and STK25 protein are up-regulated by H2O2
      stimulation, and that co-expression of the proteins accelerates cell apoptosis.
      The induction of small interfering PDCD10 (siPDCD10) or siSTK25 results in
      decreased endogenous PDCD10 and STK25 expression, which is accompanied by
      attenuated cell apoptosis. Interaction between PDCD10 and STK25 modulates ERK
      activity under oxidative stress. PDCD10 stabilizes STK25 protein through a
      proteasome-dependent pathway. Our findings suggest that PDCD10 might be a
      regulatory adaptor required for STK25 functions, which differ distinctly
      depending on the redox status of the cells that may be potentially related to
      tumor progression.

PMID- 22652781
TI  - IL-6, IL-17 and STAT3: a holy trinity in auto-immunity?
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the regulation of the
      cross talk between haematopoietic/immune cells and stromal cells, including the
      onset and resolution of inflammation, responses to infection, tissue remodelling
      and cancer. It is produced, among others, by fibroblasts, endothelial cells,
      macrophages and lymphocytes. IL-6 can interact with both membrane-bound and
      soluble forms of its ligand-binding receptor, the IL-6Ralpha, triggering
      signalling via dimerization of gp130, the signalling subunit of the IL-6 receptor
      complex. This leads to the activation of the JAK/STAT pathway and mainly
      culminates in the activation of the STAT3 transcription factor. Both IL-6 and
      STAT3 have recently emerged as main regulators of the differentiation and
      function of Th17 cells, via a positive feedback loop enhancing expression and/or
      activation of IL-6 itself, IL-17 and STAT3. Dysregulated IL-6 production and
      signalling are associated with chronic inflammatory diseases, auto-immunity and
      cancer, and are the object of intense translational research as promising
      therapeutic targets.

PMID- 22652783
TI  - Role of miR-155 in breast cancer.
AB  - Breast cancer is the second leading cause of death due to cancer in women.
      Accumulating evidence shows a correlation between overexpression of miR-155 and
      breast cancer development. The microRNA (miRNA) encoded by mir-155 is known to be
      oncogenic in multiple tumors. This review summarizes the signaling pathways that
      are regulated by miR-155 in breast cancer and discusses therapeutic possibilities
      related to miR-155.

PMID- 22652784
TI  - Obesity-related hepatocellular carcinoma: roles of risk factors altered in
      obesity.
AB  - Epidemiological data have demonstrated that the prevalence of either obesity or
      hepatocellular carcinoma (HCC) is increasing worldwide during past decades, and
      obesity has been unequivocally shown to be a risk factor for HCC. It has been
      reported that a significant proportion of HCC in obesity develops in cryptogenic
      cirrhosis, which is largely associated with the progression of nonalcoholic fatty
      liver disease, especially nonalcoholic steatohepatitis. Since the HCC is a highly
      malignant tumor with a poor prognosis, a better understanding of the molecular
      mechanisms may help researchers to explore new approaches for preventing and
      treating the obesity-related HCC, and thereby facilitating a substantial
      reduction of morbidity and mortality. In this article, we reviewed the mechanisms
      underlying the relationship between obesity and HCC, with an emphasis on the
      roles of insulin/insulin-like growth factor axis, adipose tissue derived
      hormones, oxidative stress, and liver stem cells. In addition, we will discuss
      the impact of life-style modification on obesity-related HCC.

PMID- 22652785
TI  - The expression and regulation of aquaporins in placenta and fetal membranes.
AB  - Previous studies by our group as well as other researchers have found expression
      of Aquaporins (AQPs) 1, 3, 8, and 9 in human chorioamniotic membranes and
      placenta. Our previous study found that the alteration of the expression of AQPs
      1, 3, 8, and 9 in placenta and fetal membranes was an adaptive response to
      maintain amniotic fluid homeostasis in case of abnormal amniotic fluid volume,
      which is likely to affect the intramembranous absorption and transport of water
      and solute from mother to fetus. However, the actual regulation mechanisms of
      intramembranous absorption and placental water flow are not yet clear, making it
      difficult to treat abnormal amniotic fluid volume effectively. Several studies
      found that many factors, including hormone levels, osmotic pressure, temperature,
      and oxygen concentration, regulate expression of AQPs in placenta, fetal
      membranes, and other mammalian organs through several signal transduction
      pathways, such as the cAMP, the MAPK, the PI3K/AKT, and the PKC pathways. These
      factors could provide potential therapeutic targets for the treatment of abnormal
      amniotic fluid volume.

PMID- 22652782
TI  - Endothelial progenitor cells in atherosclerosis.
AB  - Endothelial progenitor cells (EPCs) are involved in the maintenance of
      endothelial homoeostasis and in the process of new vessel formation. 
      Experimental and clinical studies have shown that atherosclerosis is associated
      with reduced numbers and dysfunction of EPCs; and that medications alone are able
      to partially reverse the impairment of EPCs in patients with atherosclerosis. 
      Therefore, novel EPC-based therapies may provide enhancement in restoring EPCs'
      population and improvement of vascular function.  Here, for a better
      understanding of the molecular mechanisms underlying EPC impairment in
      atherosclerosis, we provide a comprehensive overview on EPC characteristics,
      phenotypes, and the signaling pathways underlying EPC impairment in
      atherosclerosis.

PMID- 22652786
TI  - Obesity and gastric cancer.
AB  - Obesity is an important public health problem worldwide. It increases the risk of
      many chronic diseases such as diabetes and cardiovascular diseases. Meanwhile,
      obesity is a major risk factor for several types of cancer including gastric
      cancer. Possible mechanisms linking obesity with gastric cancer may include
      obesity associated gastro-oesophageal reflux, insulin resistance, altered levels
      of adiponectin, leptin, ghrelin, and an abnormally increased blood level of
      insulin-like growth factor (IGF). Helicobacter pylori (H. pylori) infection is a
      well-recognized risk factor for peptic ulcer and gastric cancer. Recent studies
      have revealed an increased prevalence of H. pylori infection in obese patients,
      providing another clue for the increased incidence of gastric cancer in obese
      population. If this connection can be confirmed in animal models and a large
      cohort of patients, then eradicating H. pylori together with life style
      modification in obese individuals may help prevent the development of gastric
      cancer in the increasingly obese population.

PMID- 22652787
TI  - Transdifferentiation of hepatic oval cells into pancreatic islet beta-cells.
AB  - Insulin production by beta-cells derived from hepatic oval cells is a promising
      new approach for the treatment of diabetes. Hepatic oval cells can be redirected
      to the beta-cell linage by an appropriate combination of high extracellular
      glucose, specific extracellular matrix proteins (laminin and fibronectin),
      cytokines (activin A), and the expression of several differentiation-related
      transcription factors (Pdx-1, Ngn-3, MafA). We explore the process of hepatic
      oval cell transdifferentiation into pancreatic islet beta-cells and the cellular
      signaling pathways involved.

PMID- 22652788
TI  - The effects of dietary flavonoids on the regulation of redox inflammatory
      networks.
AB  - Dietary flavonoids are a large family of polyphenols ubiquitously expressed in
      plants. Recent evidence show that flavonoids possess several anti-inflammatory
      activities due to their ability to scavenge reactive oxygen and nitrogen species
      (ROS and RNS), to inhibit the pro-inflammatory activity of ROS-generating enzymes
      including cyclooxygenase (COX), lipoxygenase (LOX) and inducible nitric oxide
      synthase (iNOS) and to modulate different intracellular signaling pathways from
      NF-kB to mitogen-activated protein kinases (MAPKs) through perturbation of redox
      sensible networks in immune cells. This report will review current knowledge on
      the anti-inflammatory effects of flavonoids on immune cells focusing on their
      ability to modulate multiple redox-sensible pathways involved in inflammation.

PMID- 22652789
TI  - Angiotensinergic neurotransmission in the peripheral autonomic nervous system.
AB  - Angiotensin (Ang) II has for long been identified as a neuropeptide located
      within neurons and pathways of the central nervous system involved in the control
      of thirst and cardio-vascular homeostasis. The presence of Ang II in ganglionic
      neurons of celiac, dorsal root, and trigeminal ganglia has only recently been
      described in humans and rats. Ang II-containing fibers were also found in the
      mesenteric artery and the heart, together with intrinsic Ang II-containing
      cardiac neurons. Ganglionic neurons express angiotensinogen and co-localize it
      with Ang II. Its intraneuronal production as a neuropeptide appears to involve
      angiotensinogen processing enzymes other than renin. Immunocytochemical and gene
      expression data suggest that neuronal Ang II acts as a neuromodulatory peptide
      and co-transmitter in the peripheral autonomic, and also sensory nervous system.
      Neuronal Ang II probably competes with humoral Ang II for effector cell
      activation. Its functional role, however, still remains to be determined.
      Angiotensinergic neurotransmission in the autonomic nervous system is a potential
      new target for therapeutic interventions in many common diseases such as
      essential hypertension, heart failure, and cardiac arrhythmia.

PMID- 22652790
TI  - The role of melatonin in acute myocardial infarction.
AB  - Melatonin, a circadian hormone with marked antioxidant properties, has been shown
      to protect against ischemia-reperfusion myocardial damage, especially when
      administered during reperfusion period. Melatonin has cardioprotective properties
      via its direct free radical scavenging and its indirect antioxidant activity.
      Melatonin efficiently interacts with various reactive oxygen and reactive
      nitrogen species and it also upregulates antioxidant enzymes and downregulates
      pro-oxidant enzymes. In addition, melatonin demonstrated blood pressure lowering,
      lipid profile normalizing and anti-inflammatory properties. The lack of these
      cardioprotective effects due to insufficient melatonin levels might be associated
      with several cardiovascular pathologies including ischemic heart disease.
      Patients with acute coronary syndrome or after myocardial infarction were shown
      to have reduced nighttime melatonin levels and 6-sulfatoxymelatonin urinary
      excretion. These alterations might translate to increased cardiovascular risk
      observed in acute myocardial infarction patients with low melatonin levels; and a
      mutation in melatonin receptors might augment the risk for acute myocardial
      infarction. Therefore, it is expected that melatonin administration could play a
      clinically relevant role in the pharmacotherapy of ischemic heart disease; an
      assumption supported by low toxicity and high safety of melatonin.

PMID- 22652791
TI  - Compound selection for in vitro modeling of developmental neurotoxicity.
AB  - Development of in vitro systems, such as those based on embryonic stem cell
      differentiation, depends on the selection of adequate test and training
      compounds. We recommend the use of two classes of positive controls, the "gold
      standard compounds" for which developmental neurotoxicity (DNT) has been proven
      in man, and the "pathway compounds" that are known to disrupt signalling pathways
      and key processes relevant for neuronal differentiation. We introduce the concept
      of toxicity endophenotypes (TEP) as changes in neuronal connectivity resulting
      from exposure to developmental toxicants. Thus, TEPs provide the scientific
      rationale for modeling DNT with simple in vitro models of key neurodevelopmental
      events. In this context, we discuss scientific and technical aspects of the test
      compound selection process. We suggest to include compounds with unspecific
      toxicity, besides negative control compounds, and we recommend tandem approaches
      to determine relative toxicities instead of absolute measures. Finally, we
      discuss how to avoid pitfalls by distinguishing between unspecific forms of
      cytotoxicity and specific developmental neurotoxicity. A compilation of compound
      lists corresponding to the above-discussed principles supplement this review.

PMID- 22652792
TI  - Mechanisms and emerging functions of DNA degradation in the epidermis.
AB  - Degradation of DNA is involved in key processes maintaining the integrity of the
      epidermis such as the cornification of keratinocytes, the removal of damaged
      cells and the defense against potentially harmful microorganisms. Recent studies
      have characterized some of the molecular mechanisms and physiological functions
      of DNA degradation in the epidermis. Deoxyribonuclease (DNase)1L2 and TREX2 were
      identified as epidermis-specific DNases and DNase 2 was shown to be the
      predominant DNA-degrading enzyme on the surface of the skin. Here we review the
      latest insights into the DNA catabolism in the skin and discuss open questions
      pertaining to the molecular biology of epidermal DNA breakdown.

PMID- 22652793
TI  - Structural biology of factor VIIa/tissue factor initiated coagulation.
AB  - Factor VII (FVII) consists of an N-terminal gamma-carboxyglutamic acid domain
      followed by two epidermal growth factor-like (EGF1 and EGF2) domains and the C
      terminal protease domain. Activation of FVII results in a two-chain FVIIa
      molecule consisting of a light chain (Gla-EGF1-EGF2 domains) and a heavy chain
      (protease domain) held together by a single disulfide bond. During coagulation,
      the complex of tissue factor (TF, a transmembrane glycoprotein) and FVIIa
      activates factor IX (FIX) and factor X (FX).  FVIIa is structurally "zymogen
      like" and when bound to TF, it is more "active enzyme-like."  FIX and FX share
      structural homology with FVII. Three structural biology aspects of FVIIa/TF are
      presented in this review. One, regions in soluble TF (sTF) that interact with
      FVIIa as well as mapping of Ca2+, Mg2+, Na+ and Zn2+ sites in FVIIa and their
      functions; two, modeled interactive regions of Gla and EGF1 domains of FXa and
      FIXa with FVIIa/sTF; and three, incompletely formed oxyanion hole in FVIIa/sTF
      and its induction by substrate/inhibitor. Finally, an overview of the recognition
      elements in TF pathway inhibitor is provided.

PMID- 22652794
TI  - Regulation of hepatic stellate cells by connective tissue growth factor.
AB  - Connective tissue growth factor (CTGF/CCN2) regulates cell proliferation,
      differentiation, adhesion, chemotaxis, migration, apoptosis and extracellular
      matrix production. Through these diverse actions, CTGF/CCN2 plays a major role in
      important physiological and pathophysiological processes such as embryogenesis,
      implantation, angiogenesis, chondrogenesis, tumorigenesis, differentiation, wound
      healing and fibrosis. Whereas hepatic levels of CTGF/CCN2 are usually low,
      elevated levels of hepatic CTGF/CCN2 occur in patients with liver fibrosis and in
      experimental animal models of liver fibrosis.  In fibrotic liver, CTGF/CCN2 is
      produced by multiple cell types but its sustained expression by and action on
      hepatic stellate cells is particularly important because these cells assume an
      activated phenotype during fibrosing injury and are principally responsible for
      the excessive production of fibrillar collagens, a process that is driven by
      CTGF/CCN2. Through its direct actions and interactions with other molecules such
      as fibronectin or transforming growth factor beta-1, CTGF/CCN2 promotes
      proliferation, survival, migration, adhesion, and extracellular matrix production
      in activated hepatic stellate cells, thereby promoting hepatic fibrogenic
      pathways. This review focuses on the regulation of hepatic stellate cell function
      by CTGF/CCN2.

PMID- 22652796
TI  - BMP2 induces PANC-1 cell invasion by MMP-2 overexpression through ROS and ERK.
AB  - The emerging roles of bone morphogenetic proteins (BMPs) in the initiation and
      progression of multiple cancers have drawn great attention in cancer research. We
      hypothesized that BMP2 promotes cancer metastasis by modulating MMP-2 secretion
      and activity through intracellular ROS regulation and ERK activation in human
      pancreatic cancer. Our data show that stimulation of PANC-1 cells with BMP2
      induced MMP-2 secretion and activation, associated with decreased E-cadherin
      expression, resulting in epithelial-to-mesenchymal transformation (EMT) and cell
      invasion. Blockade of ROS by the ROS scavenger, 2-MPG, abolished cell invasion,
      inhibited the EMT process and decreased MMP-2 expression, suggesting ROS
      accumulation caused an increase in MMP-2 expression in BMP2-stimulated PANC-1
      cell invasion. Furthermore, treatment of PANC-1 cells with 2-MPG or ERK inhibitor
      PD98059 reduced the phosphorylation of ERK, resulting in attenuation of BMP2
      induced cell invasion and MMP-2 activation. Taken together, these results suggest
      that BMP2 induces the cell invasion of PANC-1 cells by enhancing MMP-2 secretion
      and acting through ROS accumulation and ERK activation.

PMID- 22652797
TI  - Association between obesity and gallbladder cancer.
AB  - Obesity has become a global health issue because of its increased morbidity and
      mortality, and a close association with at least 20 different cancers. Clinical
      and epidemiological studies have suggested that obesity and overweight are
      positively related with the risk of GBC. Gallbladder cancer (GBC) is a relatively
      infrequent but highly lethal neoplasm. Obesity may disturb lipid and endogenous
      hormones metabolism, affect gallbladder motility, increase the risk of
      gallstones, and thus plays a role in GBC. Control of obesity through measures
      such as lifestyle modification, healthy diet, and regular exercise may prove
      useful in the prevention of GBC.

PMID- 22652798
TI  - The origins of vacularization in tumors.
AB  - Vascularization is crucial for tumor growth and metastasis. Angiogenesis and
      vasculogenesis are widely accepted processes of tumor vascularization,
      particularly for endothelium-dependent vessels. In both these processes, the
      tumor vascular endothelial cells are derived from the host cells, including cells
      in normal tissues around the tumor or endothelial progenitor cells. In addition,
      the mosaic vessels occur as a transitional pattern between endothelium-dependent
      vessels and vasculogenic mimicry (VM), wherein both host endothelium and tumor
      cells participate in tumor vascularization. VM provides a special passage not
      involving endothelial cells and is conspicuously different from angiogenesis and
      vasculogenesis. The biological features of the tumor cells that form VM remain
      unknown. Tumor stem cells may participate in VM. In this review, we discuss the
      patterns involved in the origin of vascularization in tumors.

PMID- 22652795
TI  - MicroRNAs: molecular features and role in cancer.
AB  - microRNAs (miRNAs) are small noncoding endogenously produced RNAs that play key
      roles in controlling the expression of many cellular proteins. Once they are
      recruited and incorporated into a ribonucleoprotein complex miRISC, they can
      target specific mRNAs in a miRNA sequence-dependent process and interfere in the
      translation into proteins of the targeted mRNAs via several mechanisms.
      Consequently, miRNAs can regulate many cellular pathways and processes.
      Dysregulation of their physiological roles may largely contribute to disease. In
      particular, in cancer, miRNAs can be involved in the deregulation of the
      expression of important genes that play key roles in tumorigenesis, tumor
      development, and angiogenesis and have oncogenic or tumor suppressor roles. This
      review focuses on the biogenesis and maturation of miRNAs, their mechanisms of
      gene regulation, and the way their expression is deregulated in cancer. The
      involvement of miRNAs in several oncogenic pathways such as angiogenesis and
      apoptosis, and in the inter-cellular dialog mediated by miRNA-loaded exosomes as
      well as the development of new therapeutical strategies based on miRNAs will be
      discussed.

PMID- 22652801
TI  - Senescence; an endogenous anticancer mechanism.
AB  - Pre-malignant tumor cells enter a state of irreversible cell cycle arrest termed
      senescence (cellular senescence; CS). CS is a part of the aging program and
      involves multiple signaling cascades and transduction mechanisms. In general,
      senescence can be divided into replicative senescence and premature senescence.
      Replicative senescence (replicative CS) has been described for all metabolically
      active cells that undergo a spontaneous decline in growth rate. Notably, ectopic
      expression of telomerase holoenzyme (hTert) can prevent replicative CS. In cancer
      cells, premature senescence induced by oncogenes, named oncogene-induced
      senescence (oncogene induced CS; OIS), play an important role in preventing the
      development of cancer. Oncogene induced CS can be promoted by the loss of tumor
      suppressor genes, such as PTEN. Additionally, other interesting mechanisms, like
      selective microRNA expression, epigenetic modifications, or even stress
      conditions, are also able to activate the senescence program. Here, we will
      critically review the literature on the role of senescence in preventing the
      development of cancer and discuss the potential of senescence modulation for
      generating new molecular tools that could be explored as anticancer treatments.

PMID- 22652802
TI  - The role of melatonin treatment in chronic kidney disease.
AB  - The pineal hormone melatonin plays a major role in circadian sleep-wake rhythm.
      Patients with Chronic Kidney Disease (CKD), especially those who are on
      hemodialysis, frequently suffer from sleep disturbances. In this review an
      overview is given of the classification of stages of chronic kidney disease,
      followed by a presentation of the circadian rhythm disorders in renal disease
      involving sleep disturbances in relation to melatonin deficiency. The therapeutic
      benefit of melatonin treatment in sleep disorders related to chronic kidney
      disease including the controlled trials solving this topic, is described.
      Furthermore, the beneficial effect of melatonin on blood pressure alterations in
      CKD states and the protection of melatonin in oxidative stress and inflammation
      in renal disorders are explored. Finally a hypothetic model is described for the
      relation between circadian rhythm disorders and CKD.

PMID- 22652803
TI  - Regulation of endochondral ossification by transcription factors.
AB  - Endochondral ossification is very unique and complex biological event which is
      associated with skeletal development and tissue partnering. Genetic studies and
      gene-targeting approaches identified several transcription factors that play
      important roles in endochondral ossification. These transcription factors
      sequentially and harmoniously regulate each step of endochondral ossification,
      and consequently maintain the spatio-temporal control of the program.
      Importantly, these transcription factors form large protein complex to control
      chromatin remodeling, histone modification, transcription and splicing steps
      during endochondral ossification. It is also important to understand how these
      transcription factors regulate expression of their target genes. Biochemical and
      molecular cloning techniques largely contributed to identification of the
      components of the transcriptional complex and the target genes. Most recently,
      importance of endoplasmic reticulum (ER) stress in endochondral ossification has
      been reported. A transcription factor, BBF2H7, functions as an ER stress sensor
      in chondrocytes through regulation of appropriate secretion of chondrogenic
      matrices. We would like to discuss how the transcription factors regulate
      endochondral ossification.

PMID- 22652804
TI  - TGF-beta 1 induced fibroblast proliferation is mediated by the FGF-2/ERK pathway.
AB  - Pulmonary fibrosis, defined as the accumulation of connective tissue in the
      lungs, is a severe and often fatal form of interstitial lung disease.
      Transforming growth factor-beta (TGF-beta) is a powerful activator of connective
      tissue synthesis and fibroblast proliferation in the lung, and a critical
      paracrine signal for the development of pulmonary fibrosis. To investigate
      signaling pathways downstream of TGF- beta that contribute to lung fibrosis, TGF-
      beta stimulation of fibroblasts was replicated by treating NIH3T3 fibroblasts
      with conditioned medium (CM) from TGF- beta -treated type II alveolar epithelial
      cells (ATII cells). The data showed that fibroblast growth factor 2 (FGF-2)
      signaling is responsible for TGF-beta 1 CM-induced fibroblast proliferation,
      while it does not affect TGF-beta 1 CM-induced fibrotic differentiation.
      Moreover, fibroblast proliferation and differentiation induced by TGF- beta CM
      was totally abrogated by pretreatment of NIH3T3 cells with the specific ERK1/2
      inhibitor, PD98059. These findings indicate that FGF-2 secreted by alveolar
      epithelial cells in response to TGF- beta 1 induces fibroblast proliferation and
      fibrotic activation through the ERK kinase pathway.

PMID- 22652799
TI  - Xin proteins and intercalated disc maturation, signaling and diseases.
AB  - Intercalated discs (ICDs) are cardiac-specific structures responsible for
      mechanical and electrical communication among adjacent cardiomyocytes and are
      implicated in signal transduction.  The striated muscle-specific Xin repeat
      containing proteins localize to ICDs and play critical roles in ICD formation and
      cardiac function. Knocking down the Xin gene in chicken embryos collapses the
      wall of developing heart chambers and leads to abnormal cardiac morphogenesis. In
      mammals, a pair of paralogous genes, Xinalpha and Xinbeta exist. Ablation of the
      mouse Xinalpha (mXinalpha) does not affect heart development. Instead, mXinalpha
      deficient mice show adult late-onset cardiac hypertrophy and cardiomyopathy with
      conduction defects. The mXinalpha-deficient hearts up-regulate mouse Xinbeta
      (mXinbeta, suggesting a partial compensatory role of mXinbeta. Complete loss of
      mXinbeta however, leads to failure of forming ICD, mis-localization of mXinalpha,
      and early postnatal lethality. In this review, we will briefly discuss recent
      advances in the anatomy and function of ICDs. We will then review what we know
      about Xin repeat-containing proteins and how this protein family promotes ICD
      maturation and stability for normal cardiac function.

PMID- 22652805
TI  - Abnormal bone metabolism in Crohn's disease.
AB  - Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative
      colitis (UC) have a major impact on the health of individuals and populations.
      These diseases result from an inappropriate immune response, in genetically
      susceptible individuals, to microbial antigens of commensal microorganisms. This
      paper reviews the abnormal bone metabolism associated with CD, in order to
      elucidate the mechanism of bone loss.

PMID- 22652800
TI  - B cell TLRs and induction of immunoglobulin class-switch DNA recombination.
AB  - Toll-like receptors (TLRs) are a family of conserved pattern recognition
      receptors (PRRs).  Engagement of B cell TLRs by microbe-associated molecular
      patterns (MAMPs) induces T-independent (TI) antibody responses and plays an
      important role in the early stages of T-dependent (TD) antibody responses before
      specific T cell help becomes available.  The role of B cell TLRs in the antibody
      response is magnified by the synergy of B cell receptor (BCR) crosslinking and
      TLR engagement in inducing immunoglobulin (Ig) class switch DNA recombination
      (CSR), which crucially diversifies the antibody biological effector functions.
      Dual BCR/TLR engagement induces CSR to all Ig isotypes, as directed by cytokines,
      while TLR engagement alone induces marginal CSR.  Integration of BCR and TLR
      signaling results in activation of the canonical and non-canonical NF-kappaB
      pathways, induction of activation-induced cytidine deaminase (AID) and germline
      transcription of IgH switch (S) regions.  A critical role of B cell TLRs in CSR
      and the antibody response is emphasized by the emergence of several TLR ligands
      as integral components of vaccines that greatly boost humoral immunity in a B
      cell-intrinsic fashion.

PMID- 22652806
TI  - Immunotherapy for tuberculosis: what's the better choice?
AB  - A Th1/Th2 imbalance in tuberculosis (TB) patients caused by a decreased Th1
      response and an increased Th2 response is a significant factor in the
      pathogenesis and development of TB. Protective immune responses to TB include
      bacteriostatic and bactericidal responses. Unfortunately, however,
      immunoprotection and immune pathology co-exist in TB patients. Immunotherapy for
      TB principally aims to restore the Th1/Th2 balance by enhancing the Th1 response
      and suppressing the excessive Th2 response. Immunotherapy for TB can be
      classified into three categories: immune-enhancing therapy using cytokines,
      immunosuppressive therapy, and immunomodulatory therapy. Immunomodulatory therapy
      targets the Th1/Th2 imbalance and includes cytokine regulation therapy, antibody
      regulation therapy, a multi-dose heat-inactivated Mycobacterium vaccae vaccine,
      thymosin hormones and a DNA vaccine. A new approach in supplementary TB
      immunotherapy is to simultaneously up-regulate the Th1 response and down-regulate
      the Th2 response. While immunotherapy can contribute to TB treatment, it may also
      cause immunopathological injury. Therefore, immunotherapy needs to be improved
      and further studied to maximize its potential.

PMID- 22652807
TI  - Phage in the diagnosis and treatment of tuberculosis.
AB  - The serious global TB epidemic coupled with limited diagnostic and therapeutic
      technologies necessitate the study of the role phage in TB treatment.
      Mycobacterium phage have been used for TB diagnosis, but the accuracy of such
      methods needs to be improved. Phage have various advantages in treating many
      kinds of bacterial infection, and coupled with the abuse and misuse of
      antibiotics, and the increasing prevalence of drug-resistant bacteria, they have
      been studied as a novel therapy to support antibiotics. The study of phage in TB
      therapy has developed from the selection of appropriate phage to the simultaneous
      use of multiple phage and even the use of purified lyase proteins. Though phage
      have great potential in TB therapy, the technology is still in the in vitro and
      animal experiment stages, and needs further study.

PMID- 22652809
TI  - Nutritional and regulatory role of branched-chain amino acids in lactation.
AB  - Optimal growth and health of suckling neonates critically depend on milk
      production by their mothers. In both humans and animals, branched-chain amino
      acids (BCAA) are not only the major components of milk proteins but are also
      nitrogenous precursors for the synthesis of glutamate, glutamine, alanine, and
      aspartate in the mammary gland. These synthetic pathways, which are initiated by
      BCAA transaminase, contribute to the high abundance of free and peptide-bound
      glutamate, glutamine, aspartate and asparagine in milk.  In mammary epithelial
      cells, the carbon skeletons of BCAA can be partially oxidized via branched-chain
      alpha-ketoacid dehydrogenase to provide energy for highly active metabolic
      processes, including nutrient transport, protein turnover, as well as lipid and
      lactose syntheses. In addition, results of recent studies indicate that BCAA play
      regulatory roles in mammary metabolism.  For example, leucine can activate the
      mammalian target of rapamycin cell signaling pathway to enhance protein synthesis
      in mammary epithelial cells. Dietary supplementation with BCAA may have great
      potential to enhance milk synthesis by the lactating mammary gland, thereby
      improving neonatal survival, growth and development.

PMID- 22652808
TI  - Expression pattern and targeting of HER family members and IGF-IR in pancreatic
      cancer.
AB  - Pancreatic cancer is still one of the most aggressive and fatal types of human
      cancer . Survival rates for patients with pancreatic cancer are extremely poor
      and one major contributing factor is the lack of specific marker(s) for the early
      detection of pancreatic cancer. Indeed, the great majority of pancreatic cancer
      cases are diagnosed at an advanced stage of the disease and these patients often
      have a poor response to treatment with conventional forms of therapy. In this
      article, we conduct a comprehensive review of the literature on the expression
      pattern, prognostic significance and predictive value of EGFR family members, IGF
      IR and their ligands in pancreatic cancer. We also discuss recent advances in
      pancreatic cancer treatments and highlight the remaining challenges as well as
      future opportunities for more effective targeting of such receptors using a
      combination of growth factor receptor specific monoclonal antibodies, small
      molecule tyrosine kinase inhibitors and other therapeutic strategies. Such
      strategies could ultimately help to overcome the development of drug resistance
      and improve the overall survival rates for patients with pancreatic cancer.

PMID- 22652810
TI  - Mechanisms of dopamine quantal size regulation.
AB  - The study of dopamine (DA) quantal size, or the amount of transmitter released
      per vesicle fusion event, has been enabled by subsecond resolution amperometric
      recordings. These methods, together with other electrophysiology techniques,
      novel optical approaches and classical molecular biology and biochemistry
      methodologies, have advanced our understanding of quantal size regulation in
      dopaminergic and other catecholaminergic systems. The presynaptic mechanisms that
      determine DA quantal size regulate two features: the amount of transmitter stored
      in each vesicle and the fraction of vesicular contents that are released per
      fusion event. The amount of vesicular DA is dependent on DA synthesis, DA
      vesicular loading and storage and on DA reuptake from the extracellular space
      upon exocytosis. The mode of vesicle fusion and the related fusion pore dynamics
      control the fraction of DA released per fusion event. We will summarize current
      understanding on the regulation of these steps by endogenous and exogenous
      factors, including drugs of abuse and DA itself.

PMID- 22652811
TI  - A nanochannel array based device for determination of the isoelectric point of
      confined proteins.
AB  - A nanochannel array based nanodevice can mimic the biological environments and
      thus unveil the natural properties, conformation and recognition information of
      biomolecules such as proteins and DNA in confined spaces. Here we report that
      porous anodic alumina (PAA) of a highly parallel nanochannel array covalently
      modified with proteins significantly modulates the transport of a negatively
      charged probe of ferricyanide due to the electrostatic interactions between the
      probes and modified nanochannel inner surface. Results show that such
      electrostatic interaction exists in a wide range of ionic strength from 1 mM to
      100 mM in 20 nm nanochannels modified with proteins (hemoglobin, bovine serum
      albumin, and goat anti-rabbit IgG secondary antibody). In addition, the maximal
      steady-state flux of the charged probe through the modified nanochannel array is
      directly related to the ionic strength which determines the electric double layer
      thickness and solution pH which modulates the nanochannel surface charge. Thus,
      the modulated mass transport of the probe by solution pH can be used to study the
      charge properties of the immobilized proteins in nanochannel confined conditions,
      leading us to obtain the isoelectric point (pI) of the proteins confined in
      nanochannels. The determined pI values of two known proteins of hemoglobin and
      bovine serum albumin are close to the ones of the same proteins covalently
      modified on a 3-mercaptopropionic acid self-assembled monolayer/gold electrode.
      In addition, the pI of an unknown protein of goat anti-rabbit IgG secondary
      antibody confined in nanochannels was determined to be 6.3. Finally, the
      confinement effect of nanochannels on the charge properties of immobilized
      proteins has been discussed.

PMID- 22652812
TI  - Spider-silk-based fabrication of nanogaps and wires.
AB  - We report on the use of spider fibers as micro- and nanostencils for the
      fabrication of nanogaps between ultrathin conductive electrodes, and as molds for
      fabrication of micro- and nanowires by deposition of evaporated gold. Atomic
      force microscopy (AFM) morphological characterization of the nanogaps is
      described, together with the measurement of the electrical behavior of both
      nanogaps and nanowires. Gaps as narrow as 20 nm, comparable to e-beam-fabricated
      gaps, with electrical resistance higher than 10(13) Omega have been obtained;
      while conductive fibers ranging from 350 nm to 1.5 MUm in diameter and
      resistances ranging from 50 MOmega to 100 Omega have been obtained and
      characterized.

PMID- 22652813
TI  - Preparation and thermoelectric properties of sulfur doped Ag2Te nanoparticles via
      solvothermal methods.
AB  - In this work, n-type Ag(2)Te nanoparticles are prepared by a solvothermal
      approach with uniform and controllable sizes, e.g. 5-15 nm. The usage of
      dodecanethiol during the synthesis effectively introduces sulfur doping into the
      sample, which optimizes the charge carrier concentration of the nanoparticles to
      >1 * 10(20) cm(-3). This allows us to achieve the desired electrical
      resistivities of <5 * 10(-6)Omega m. It is demonstrated that Ag(2)Te particles
      prepared by this solvothermal process can exhibit high ZT values, e.g. 15 nm
      Ag(2)Te nanoparticles with effective sulphur doping show a maximum ZT value of
      ~0.62 at 550 K.

PMID- 22652814
TI  - An exonic peroxisome proliferator-activated receptor-gamma coactivator-1alpha
      variation may mediate the resting energy expenditure through a potential
      regulatory role on important gene expression in this pathway.
AB  - BACKGROUND/AIMS: We studied peroxisome proliferator-activated receptor-gamma
      coactivator-1alpha (PPARGC1A) gene variations at the 23815227-23815706 positions
      and examined their possible correlation with obesity-related conditions and
      resting energy expenditure (REE). We investigated the expression of PPARGC1A,
      mitogen-activated protein kinase (MAPK) and uncoupling protein 2 (UCP2), which
      play key roles in cellular energy expenditure, in a cellular model consisting of
      peripheral blood mononuclear cells, and compared them with various genotypes of
      the PPARGC1A gene. METHODS: In total, 100 normal-weight and 129 obese subjects
      participated in the current study. All subjects were assessed for REE and body
      composition. We sequenced the PPARGC1A gene. Real-time PCR was used for
      determining the PPARGC1A, MAPK, and UCP2 gene expression. RESULTS: There were
      significant differences in terms of body mass index, fat mass, low-density
      lipoprotein, insulin levels, REE/kg body weight, and REE/lean body mass among
      rs17574213 genotypes. There were significant differences in total cholesterol and
      low-density lipoprotein cholesterol levels among the various genotypes of
      Gly482Ser (rs8192678) and rs3755863. The relative PPARGC1A, MAPK, and UCP2 gene
      expressions had similar trends in the two studied SNPs, and the expression level
      of these genes was lowest in the TT genotype of Gly482Ser and rs3755863 and
      highest in the CC genotype of Gly482Ser and rs3755863. CONCLUSIONS: Our findings
      suggest that PPARGC1A variations may influence PPARGC1A expression and the
      coordinating regulators of downstream targets in energy homeostasis. Further
      study is needed to shed some light on this process.

PMID- 22652821
TI  - Rosai-Dorfman disease: a retrospective analysis of 13 cases.
AB  - BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, idiopathic, histiocytic
      proliferative disorder, the infrequent occurrence of which limits in-depth
      studies. Consequently, many characteristics of this disease remain unknown,
      restricting early diagnosis and proper treatment. METHODS: In this study, the
      literature was reviewed and a retrospective analysis of the medical records of 13
      patients with RDD conducted to investigate the demographic data, clinical data,
      laboratory and imaging results, treatment, and prognosis of this disease.
      RESULTS: Of the 13 cases in our sample, 10 (77%) were purely extranodal RDD, 2
      (15%) were both nodal and extranodal, and 1 (8%) was purely nodal. The locations
      of the 10 purely extranodal RDD lesions included the central nervous system (n =
      6, 60%), nasal cavity and paranasal sinuses (n = 3, 30%), and the cutis (n = 1,
      10%). The locations of the central nervous system-related RDD lesions included
      the cerebral subdura (n = 2, 29%), the sellar region (n = 3, 14%), the cerebral
      parenchyma (n = 1, 14%) and the spinal subdura (n = 1, 14%). Ten patients (77%)
      had stable conditions, 3 (23%) experienced recurrence, and 2 (15%) experienced
      recurrence and lesion metastasis. CONCLUSIONS: RDD is rare, requiring knowledge
      of its clinical manifestations for a rapid and correct diagnosis. In light of the
      possibility of recurrence and lesion metastasis, long-term follow-up is needed.
      Treatment is still controversial. Future efforts should be directed at
      investigating the etiology and postoperative treatment for relapsing cases or
      those with subresected lesions.

PMID- 22652820
TI  - Frequency, risk factors and prognosis of postoperative hyperbilirubinemia after
      heart valve surgery.
AB  - OBJECTIVES: Despite recent advances in cardiovascular surgery, hyperbilirubinemia
      after heart valve surgery occurs often and the mechanism is not well clarified.
      We evaluated the incidence and nature of postoperative hyperbilirubinemia in
      heart valve surgery patients to analyze its risk factors and to identify its
      clinical significance for associated morbidity and mortality. METHODS: We
      investigated 334 consecutive patients who underwent heart valve surgery.
      Postoperative hyperbilirubinemia was defined as total serum bilirubin
      concentration greater than 3 mg/dl at any postoperative measurement point.
      RESULTS: Postoperative hyperbilirubinemia developed in 63 patients (19.0%) and
      was associated with greater in-hospital mortality (15.9 vs. 1.5%, p < 0.01).
      Univariate analysis revealed congestive heart failure history, cardiogenic shock,
      infective endocarditis, preoperative liver dysfunction, longer cardiopulmonary
      bypass time and transfusion as significantly related to postoperative
      hyperbilirubinemia. In multivariate analysis, preoperative liver dysfunction
      [odds ratio (OR) 6.5, p < 0.05] and longer cardiopulmonary bypass time (OR 1.007,
      p < 0.01) were independent predictors. In postoperative hyperbilirubinemia
      patients, preoperative New York Heart Association status and history of heart
      failure were associated with outcome. CONCLUSIONS: Postoperative
      hyperbilirubinemia remains common in patients undergoing heart valve surgery and
      is associated with a high rate of in-hospital mortality. For patients with heart
      failure or liver dysfunction, meticulous operative management is required to
      reduce cardiopulmonary bypass time and transfusion.

PMID- 22652822
TI  - Investigations of mercury concentrations in walleye and other fish in the
      Athabasca River ecosystem with increasing oil sands developments.
AB  - Recent studies have reported an increasing trend of mercury concentrations in
      walleye (Sander vitreus) from the Athabasca River, north eastern Alberta
      (Canada); these studies were based on three years of comparison and attributed
      the mercury increase to expanding oil sands developments in the region. In order
      to conduct a more comprehensive analysis of mercury trends in fish, we compiled
      an extensive database for walleye, lake whitefish (Coregonus clupeaformis),
      northern pike (Esox lucius) and lake trout (Salvelinus namaycush) using all
      available data obtained from provincial, federal, and industry-funded monitoring
      and other programs. Evidence for increasing trends in mercury concentrations were
      examined for each species by location and year also considering fish weight and
      length. In the immediate oil sands area of the Athabasca River, mercury
      concentrations decreased (p < 0.001) in walleye and lake whitefish over 1984
      2011. In western Lake Athabasca and its delta, mercury concentrations decreased
      (p < 0.0001) in northern pike (1981-2009) although no trend was evident for
      walleye (1981-2005) and lake trout (1978-2009). Mercury concentrations in lake
      trout from Namur Lake, a small lake west of the oil sands area, were higher in
      2007 than 2000 (p < 0.0001); it is difficult to ascribe this increase to an oil
      sands impact because similar increases in mercury concentrations have been
      observed in lake trout from similar sized lakes in the Northwest Territories.
      While mercury emissions rates have increased with oil sands development and the
      landscape become more disturbed, mercury concentrations remained low in water and
      sediments in the Athabasca River and its tributaries and similar to
      concentrations observed outside the development areas and in earlier decades. Our
      fish database was assembled from a series of studies that differed in study
      purpose, design, and analytical methods. Future monitoring programs investigating
      mercury trends in fish should be more rigorous in their design.

PMID- 22652823
TI  - Breastfeeding and determinants of adult body composition: a prospective study
      from birth to young adulthood.
AB  - BACKGROUND: The impact of breastfeeding on adult body composition is
      controversial. We evaluated effects of lifestyle and childhood-related factors,
      including infant feeding, on adult body composition. METHODS: We determined total
      body and trunk fat and lean mass by densitometry in 158 adults who were born full
      term and prospectively followed from birth to the age of 32 years. Data on
      various factors, extending from infancy to adulthood, with potential effect on
      body composition, were recorded. RESULTS: Scapular skinfold thickness at 12
      months correlated with adult trunk (R = 0.22, p = 0.005) and body fat percentage
      (R = 0.18, p = 0.023). In linear regression analysis, current physical activity
      (R = -0.33, p < 0.001) and maternal BMI (R = 0.28, p = 0.002) were associated
      with adult body fat percentage. Gender (R = 0.78, p < 0.001) and weight gain
      during infancy (R = 0.147, p = 0.008) were associated with adult lean mass. In
      the analysis of covariance, prolonged breastfeeding tended to lead to lower fat
      percentage in adulthood, but no direct association with the duration of
      breastfeeding and adult body composition was confirmed. CONCLUSIONS: Current
      physical activity, growth in infancy, gender and maternal BMI influence adult
      body composition. Breastfeeding has an indirect influence on adult body fat
      accumulation by affecting growth and body adiposity in infancy.

PMID- 22652824
TI  - Hydrogen distribution in Nb/Ta superlattices.
AB  - The distribution of hydrogen in Nb/Ta superlattices has been investigated by
      combined neutron reflectivity and x-ray scattering. We provide evidence to
      support that strain modulations determined with x-ray diffraction can be
      interpreted as modulations in hydrogen content. We show that the hydrogen
      concentration is modulated and favors Nb, in agreement with previous studies. We
      measure the concentration directly using neutron reflectivity and demonstrate no
      detectable change in the distribution of hydrogen with temperature, in stark
      contrast to previous studies.

PMID- 22652825
TI  - Effect of physiological exercise on osteocalcin levels in subjects with adrenal
      incidentaloma.
AB  - AIM: In the present study, we have evaluated whether physical exercise affect low
      osteocalcin concentrations observed in patients with subclinical
      hypercortisolism. SUBJECTS AND METHODS: Sixteen patients (10 men and 6 women, age
      38-55 yr) with adrenal incidentaloma were studied. Fifteen healthy volunteers
      matched for age (range 35-47 yr) were used as controls. Subjects were submitted
      to a 8-week exercise-training program with cycle-ergometer for 1 h/day 3-4
      days/week at 60% of their individual VO2 max. Before and after this period,
      resting venous serum osteocalcin and GH concentrations were measured in the same
      batch. The blood sampling after 8 weeks of the training program were performed
      after resting for one day. All patients and controls underwent also the following
      endocrine evaluation: serum cortisol, plasma ACTH. RESULTS: Our results
      demonstrate a significant increase of osteocalcin after physical exercise and a
      positive correlation between osteocalcin and GH. This later might suggest a role
      of GH in the increased osteocalcin secretion. CONCLUSIONS: The data of the
      present study suggest a positive effect of physical exercise on bone metabolism
      in patients with adrenal incidentaloma.

PMID- 22652827
TI  - Acute adrenal insufficiency in a neonate with bilateral adrenal hemorrhage and
      combined prothrombotic risk factors.

PMID- 22652828
TI  - Endocrinology and art. The hermaphrodite figure in the National Archeological
      Museum of Melfi.

PMID- 22652831
TI  - Alloyed Mn-Cu-In-S nanocrystals: a new type of diluted magnetic semiconductor
      quantum dots.
AB  - A new type of Mn-Cu-In-S diluted magnetic semiconductor quantum dots was
      synthesized and reported for the first time. The quantum dots, with no highly
      toxic elements, not only show the same classic diluted magnetic behavior as Mn
      doped CdSe, but also exhibit tunable luminescent properties in a relatively large
      window from 542 to 648 nm. An absolute photoluminescence quantum yield up to 20%
      was obtained after the shell growth of ZnS. This kind of magnetic/luminescent bi
      functional Mn-Cu-In-S/ZnS core/shell quantum dot might serve as promising
      nanoprobes for use in dual-mode optical and magnetic resonance imaging
      techniques.

PMID- 22652826
TI  - Advances in the epidemiology, pathogenesis, and management of Cushing's syndrome
      complications.
AB  - Cushing's syndrome (CS) is a clinical condition resulting from chronic exposure
      to glucocorticoid excess. As a consequence, hypercortisolism contributes
      significantly to the early development of systemic disorders by direct and/or
      indirect effects. Complications such as obesity, hypertension, diabetes,
      dyslipidemia, and hypercoagulability cause premature atherosclerosis and increase
      cardiovascular mortality. Impairment of the skeletal system is a relevant cause
      of morbidity and disability in these patients especially due to the high
      prevalence of vertebral fractures. In addition, muscle weakness, emotional
      lability, depression, and impairment of quality of life are very common. Clinical
      management of these patients is complex and should be particularly careful in
      identifying global cardiovascular risks and aim at controlling all complications.
      Although the primary goal in the prevention and treatment of complications is the
      correction of hypercortisolism, treatment does not completely eliminate these
      comorbidities. Given that cardiovascular risk and fracture risk can persist after
      cure, early detection of each morbidity could prevent the development of
      irreversible damage. In this review we present the various complications of CS
      and their pathogenetic mechanisms. We also suggest the clinical management of
      these patients based on our extensive clinical experience and on the available
      literature.

PMID- 22652832
TI  - Identification of functional CNV region networks using a CNV-gene mapping
      algorithm in a genome-wide scale.
AB  - MOTIVATION: Identifying functional relation of copy number variation regions
      (CNVRs) and gene is an essential process in understanding the impact of genotypic
      variations on phenotype. There have been many related works, but only a few
      attempts were made to normal populations. RESULTS: To analyze the functions of
      genome-wide CNVRs, we applied a novel correlation measure called Correlation
      based on Sample Set (CSS) to paired Whole Genome TilePath array and messenger RNA
      (mRNA) microarray data from 210 HapMap individuals with normal phenotypes and
      calculated the confident CNVR-gene relationships. Two CNVR nodes form an edge if
      they regulate a common set of genes, allowing the construction of a global CNVR
      network. We performed functional enrichment on the common genes that were trans
      regulated from CNVRs clustered together in our CNVR network. As a result, we
      observed that most of CNVR clusters in our CNVR network were reported to be
      involved in some biological processes or cellular functions, while most CNVR
      clusters from randomly constructed CNVR networks showed no evidence of functional
      enrichment. Those results imply that CSS is capable of finding related CNVR-gene
      pairs and CNVR networks that have functional significance. AVAILABILITY:
      http://embio.yonsei.ac.kr/~ Park/cnv_net.php. CONTACT: sanghyun@cs.yonsei.ac.kr
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22652833
TI  - Clinical relations of methotrexate pharmacokinetics in the treatment for
      pediatric osteosarcoma.
AB  - PURPOSE: High-dose methotrexate (HD-MTX) with leucovorin rescue is widely used to
      treat osteosarcoma. Our objectives were to assess correlations between
      pharmacokinetic parameters and the outcome of osteosarcoma and to analyze the
      relation between HD-MTX exposure and toxicity. METHODS: Pharmacokinetic data of
      105 patients with osteosarcoma treated with 989 HD-MTX courses were evaluated.
      Pharmacokinetic parameters (clearance, half-life and AUC) were calculated based
      on methotrexate (MTX) serum levels measured at 6, 24, 36, 48 h after the
      initiation of the infusion. Clinical data were collected by retrospective chart
      review. Hepato-, nephro- and bone marrow toxicity parameters were categorized
      according to Common Toxicity Criteria v.3.0, and MTX dose intensity was
      calculated. Event-free survival (EFS) and overall survival (OS) were estimated
      according to the Kaplan-Meier method. RESULTS: Patients with serious
      hepatotoxicity had higher mean peak MTX concentrations (p < 0.0001), 24-h (p =
      0.001) and 48-h MTX serum levels (p = 0.008) and AUC(0-48) (p < 0.0001), and
      lower MTX clearance (p = 0.0002). No significant association was found between
      toxicity and age, gender, presence of metastases or histological tumor response.
      Patients with higher 48-h MTX serum levels had significantly better OS and EFS.
      Higher dose intensity was associated with better EFS (p = 0.0504). There was no
      association between presence of toxicity and survival. CONCLUSION: There was
      correlation between MTX exposure and the incidence of toxicity. Higher serum
      concentrations at 48 h were associated with a better 5-year OS and EFS. These
      results suggest that higher MTX exposure may lead to serious side effects, but it
      also improves treatment outcome.

PMID- 22652836
TI  - The human story of aortic stenosis: a time for new surrogate markers in clinical
      decision making.

PMID- 22652837
TI  - Ruthenium(II) [3 + 2 + 1] mixed ligand complexes: substituent effect on
      photolability, photooxidation of bases, photocytotoxicity and photonuclease
      activity.
AB  - Mixed ligand complexes of ruthenium(II), [Ru(itpy)(bpy)Cl]ClO(4)1,
      [Ru(itpy)(phen)Cl]ClO(4)2, [Ru(bitpy)(bpy)Cl]ClO(4)3 and
      [Ru(bitpy)(phen)Cl]ClO(4)4 have been synthesized and characterized. Complex 3 has
      also been characterized crystallographically. These complexes exhibit
      photolability of the Ru-Cl bond. Upon irradiation at 440 nm in the presence of
      nucleosides and nucleotides the complexes exchange chloride for the nucleoside or
      nucleotide. The photolability of the Ru-Cl bond depends on the nature of the
      substituent in the tridentate tpy ligand. Photolysis of the complexes in the
      presence of a nucleoside or nucleotide also produces 8-oxoguanine due to the
      oxidation of guanine by the excited states of the complexes. These four complexes
      exhibit photonuclease properties and bring about the cleavage of plasmid DNA when
      irradiated at 440 nm. These complexes have been found to be toxic towards NIH 3T3
      cells under photolytic conditions.

PMID- 22652838
TI  - The use of a Ga+ focused ion beam to modify graphene for device applications.
AB  - In this work, we clarify the features of the lateral damage of line defects in
      single layer graphene. The line defects were produced through well-controlled
      etching of graphene using a Ga(+) focused ion beam. The lateral damage length was
      obtained from both the integrated intensity of the disorder induced Raman D band
      and the minimum ion fluence. Also, the line defects were characterized by
      polarized Raman spectroscopy. It was found that graphene is resilient under the
      etching conditions since the intensity of the defect induced Raman D peak
      exhibits a dependence on the direction of the lines relative to the crystalline
      lattice and also on the direction of the laser polarization relative to the
      lines. In addition, electrical measurements of the modified graphene were
      performed. Different ion fluences were used in order to obtain a completely
      insulating defect line in graphene, which was determined experimentally by means
      of charge injection and electric force microscopy measurements. These studies
      demonstrate that a Ga+ ion column combined with Raman spectroscopy is a powerful
      technique to produce and understand well-defined periodic arrays of defects in
      graphene, opening possibilities for better control of nanocarbon devices.

PMID- 22652839
TI  - Recent developments in yeast cell surface display toward extended applications in
      biotechnology.
AB  - Yeasts are promising hosts for industrial bio-refinery applications. In yeast
      cell surface displays, functional proteins, such as cellulases or lipases, are
      genetically fused to an anchor protein and expressed on the cell surface.
      Saccharomyces cerevisiae is the most commonly used yeast for cell surface
      display. Engineered yeasts have been utilized for a variety of applications, such
      as bioethanol production, chemicals synthesis, adsorption of environmental
      pollutants, and protein evolution. Here, we summarize recent developments in
      yeast cell surface display techniques for bio-refinery applications, including
      methods using hosts such as Pichia pastoris, Yarrowia lipolytica, and S.
      cerevisiae, focusing on the characteristics of anchor proteins and applications.

PMID- 22652842
TI  - Relationship of retinal vessel caliber to cardiovascular disease and mortality in
      African Americans with type 1 diabetes mellitus.
AB  - OBJECTIVE: To examine the relationship between retinal arteriolar and venular
      diameter and the 6-year incidence of cardiovascular disease and mortality among
      African Americans with type 1 diabetes mellitus. METHODS: Included were 468
      African Americans with type 1 diabetes mellitus who participated in the New
      Jersey 725 and who had undergone a 6-year follow-up examination. At both baseline
      and 6-year follow-up, hypertension and presence of heart disease, stroke, or
      lower extremity arterial disease (LEAD) were documented and confirmed by review
      of hospital admission and medical records. Computer-assisted grading from
      digitized images of retinal photographs was accomplished to determine the average
      diameter of retinal arterioles (central retinal arteriolar equivalent) and
      venules (central retinal venular equivalent). Retinal vessel diameter size was
      examined in relation to the 6-year incidence of hypertension, any cardiovascular
      disease (heart disease, stroke, or LEAD), heart disease or stroke, LEAD, and
      mortality. RESULTS: Narrower central retinal arteriolar equivalent at baseline
      significantly and independently predicted 6-year incidence of any cardiovascular
      disease and LEAD, whereas larger retinal venular diameter at baseline
      significantly and independently predicted 6-year incidence of hypertension.
      Proteinuria and retinopathy severity at baseline were stronger predictors of
      mortality than retinal vascular diameter. CONCLUSION: In African Americans with
      type 1 diabetes mellitus, baseline retinal vessel caliber is an independent
      predictor of incident hypertension and LEAD.

PMID- 22652844
TI  - Intravenous chemoreduction or intra-arterial chemotherapy for cavitary
      retinoblastoma: long-term results.
AB  - OBJECTIVE: To assess the long-term results of chemotherapy for cavitary
      retinoblastoma. METHODS: Retrospective, nonrandomized, interventional case series
      of 26 cavitary retinoblastomas in 25 eyes of 24 patients. Retinoblastomas were
      treated with intravenous chemoreduction and/or intra-arterial chemotherapy. Main
      outcome measures included tumor control, globe salvage, and metastasis. RESULTS:
      Of 24 patients with cavitary retinoblastoma, the mean age at diagnosis was 16
      months. The mean number of cavitary tumors per eye was 1 (median, 1; range, 1-2),
      with a mean tumor basal diameter of 13 (median, 13; range, 7-24) mm and mean
      tumor thickness of 7 (median, 6; range, 3-17) mm. The mean number of cavities per
      tumor was 2 (median, 2; range, 1-5), with a mean cavity diameter of 3 (median, 2;
      range, 1-10) mm. Related features included vitreous seeds in 7 tumors (27%),
      subretinal seeds in 6 (23%), and subretinal fluid in 13 (50%). Intravenous
      chemoreduction was used in 23 tumors (88%); intra-arterial chemotherapy, in 2
      (8%); and both, in 1 (4%). After treatment, the mean reduction in tumor base was
      22% and mean reduction in tumor thickness was 29%. Despite minimal reduction,
      tumor recurrence was noted in only 1 eye (4%), globe salvage was achieved in 22
      (88%), and there were no cases of metastasis or death during 49 (range, 6-189)
      months of follow-up. CONCLUSION: Despite minimal visible tumor response to
      chemotherapy, cavitary retinoblastoma displays relatively stable long-term
      results.

PMID- 22652845
TI  - Multicenter study of infliximab for refractory uveoretinitis in Behcet disease.
AB  - OBJECTIVE: To describe the effects of infliximab on refractory uveoretinitis in
      patients with Behcet disease during the first year of treatment. METHODS: Data
      were collected prospectively at 8 tertiary uveitis centers. Safety was analyzed
      in 63 patients. Efficacy was analyzed in 50 patients, after exclusion of those
      who had received infliximab for various reasons before the study. RESULTS: Eighty
      nine percent (56 of 63) of the patients were male, with 70% (44 of 63) of the
      patients aged 25 to 44 years. The safety analysis demonstrated that 34 episodes
      of adverse effects occurred in 46% (29 of 63) of patients during 1 year,
      including 3 episodes of infusion reactions. No adverse effects were deemed
      serious. The efficacy analysis at 1 year showed that uveoretinitis had improved
      in 69% (33 of 48), had improved somewhat in 23% (11 of 48), was unchanged in 8%
      (4 of 48), and had worsened in no patients. The mean number of ocular attacks per
      6-month period decreased from 2.66 at baseline to 0.44 during months 1 through 6
      of infliximab therapy and to 0.79 during months 7 through 12. Forty-four percent
      (21 of 48) of patients had no ocular attacks during the 1-year period. Efficacy
      was best for patients with uveoretinitis duration of less than 5 years. The mean
      best-corrected visual acuity improved logarithm of the minimum angle of
      resolution from 0.736 at the first infliximab infusion to 0.616 at the end of 1
      year (P = .01). CONCLUSIONS: Infliximab treatment for Behcet disease
      uveoretinitis was well tolerated, with nonserious adverse effects occurring in
      about half of the patients. At the end of 1 year, uveoretinitis had improved or
      improved somewhat in 92% (44 of 48) of patients, accompanied by improvement in
      the mean visual acuity.

PMID- 22652846
TI  - Predictive value of the seventh edition American Joint Committee on Cancer
      staging system for conjunctival melanoma.
AB  - OBJECTIVE: To evaluate the predictive value of the seventh edition American Joint
      Committee on Cancer (AJCC) staging system for conjunctival melanoma. METHODS:
      Retrospective, observational case series of 42 eyes of 42 patients with
      conjunctival melanoma studied by reviewing medical records, pathology reports,
      and color photographs. The main evaluated outcomes were demographic information,
      laterality, tumor size, thickness, pathologic diagnosis, seventh edition AJCC
      stage (clinical and pathologic), recurrence, metastasis, and duration of follow
      up. RESULTS: There was no sex preference, and the median age was 61 years.
      Recurrent disease was noted in 33% of patients (n = 14 of 42), with 64% occurring
      at a median of 2.5 years (range, 1-5 years) after primary treatment. Metastasis
      was noted in 19% of patients. The significant predictive factors for high risk of
      tumor recurrence were tumors involving more than 1 quadrant (P = .02), tumors
      thicker than 0.5 mm (P = .04), and tumor multifocality (P = .04). The significant
      predictive factors for high risk of tumor metastasis were tumors thicker than 0.5
      mm (P = .005), tumor invasiveness (P = .04), pathologic diagnosis of conjunctival
      melanoma rather than melanoma in situ (P = .04), and tumor recurrence (P < .001).
      Similarly, increasing AJCC T stages (clinical and pathologic) were associated
      with unfavorable outcomes. For example, clinical stage-related recurrence rates
      were 19% (Tis), 27% (T1), 33% (T2), and 75% (T3). Clinical stage-related
      lymphatic and distant metastasis rates were 0% (Tis), 20% (T1), 0% (T2), and 63%
      (T3). CONCLUSIONS: Advanced AJCC T-stage (clinical and pathologic) tumors were at
      higher risk for recurrence and metastasis. In this study, the seventh edition
      AJCC staging system was predictive of local control and systemic spread of
      conjunctival melanoma.

PMID- 22652847
TI  - Trends in the indications for corneal graft surgery in the United Kingdom: 1999
      through 2009.
AB  - OBJECTIVE: To examine trends in the indications for corneal graft surgery in the
      United Kingdom. METHODS: National Health Service Blood and Transplant data were
      analyzed for keratoplasty operations performed in the United Kingdom between
      April 1, 1999, and March 31, 2009, distinguishing the type of graft and the
      surgical indication. RESULTS: The total number of annual keratoplasty operations
      increased from 2090 in 1999-2000 to 2511 in 2008-2009. Among these, the annual
      number of grafts performed for endothelial failure increased from 743 (35.6%) in
      1999-2000 to 939 (37.4%) in 2008-2009. The performance of penetrating
      keratoplasty (PK) for endothelial failure decreased from 98.3% of all grafts in
      1999-2000 to 46.6% of all grafts in 2008-2009, while the performance of
      endothelial keratoplasty increased from 0.3% of all grafts in 1999-2000 to 51.2%
      of all grafts in 2008-2009. The annual number of grafts performed for keratoconus
      increased from 514 (24.6%) in 1999 to 564 (22.5%) in 2008-2009. The performance
      of PK for keratoconus decreased from 88.4% of all grafts in 1999-2000 to 57.1% of
      all grafts in 2008-2009, while the performance of deep anterior lamellar
      keratoplasty increased from 8.8% of all grafts in 1999-2000 to 40.1% of all
      grafts in 2008-2009. The number of annual regraft operations increased from 249
      (11.9%) in 1999-2000 to 401 (16.0%) in 2008-2009, most commonly for endothelial
      failure. In 2008-2009, PK regrafts (78.1%) far outnumbered endothelial
      keratoplasty regrafts (17.0%). CONCLUSIONS: Endothelial failure is the most
      common indication for keratoplasty in the United Kingdom, and endothelial
      keratoplasty is performed more commonly than PK for this indication. The number
      of grafts performed for pseudophakic bullous keratopathy has remained stable,
      while the number of grafts performed for Fuchs endothelial dystrophy is likely to
      continue increasing. Keratoconus is the second most common indication for
      keratoplasty, and deep anterior lamellar keratoplasty numbers are approaching
      those for PK. Regraft surgery is the third most common indication for
      keratoplasty, required in most cases because of endothelial failure.

PMID- 22652848
TI  - Health services utilization and cost of retinitis pigmentosa.
AB  - OBJECTIVE: To estimate annual per-patient health services utilization and costs
      of retinitis pigmentosa (RP) in the United States. METHODS: A retrospective
      claims analysis of patients with RP (N = 2990) and a 1:1 exactly matched cohort
      of non-RP patients was conducted using the MarketScan Commercial and Medicare
      Supplemental Databases. Individuals were continuously enrolled in a commercial
      health plan or employer-sponsored health insurance for at least 1 year. The
      following annual outcomes were analyzed using nonlinear multivariate models:
      inpatient hospital admissions, inpatient hospital days, emergency department
      visits, outpatient physician visits, and prescription drug refills and inpatient
      and outpatient medical, pharmacy, and total health care costs. RESULTS: Patients
      with RP had 0.04 more hospital admissions (P < .001), 0.19 more inpatient
      hospital days (P < .02), 0.05 more emergency department visits (P < .01), 2.74
      more outpatient visits (P < .001), and 2.18 additional prescription drug fills (P
      < .001) annually compared with their non-RP counterparts. Health care
      expenditures were significantly higher for patients with RP, who cost $894,
      $4855, and $452 more for inpatient, outpatient, and pharmacy services,
      respectively (P < .001). Overall health care costs were $7317 more per patient
      per year in the RP cohort, with expenditures varying considerably by age.
      CONCLUSIONS: Patients with RP consume substantially greater amounts of health
      services with significantly higher health care costs. CLINICAL RELEVANCE:
      Treatments that slow, halt, or possibly restore RP-related vision loss may prove
      cost-effective for payers and society.

PMID- 22652849
TI  - Use of adhesive tape for temporary management of inturned upper eyelid eyelashes.
AB  - OBJECTIVE: To evaluate the efficacy of adhesive tape for temporary management of
      inturned upper eyelid eyelashes. METHODS: In a prospective, consecutive,
      comparative, nonrandomized, interventional case series, 50 patients (100 eyes)
      had inturned eyelashes with at least 1 of 3 symptoms: foreign body sensation,
      itchiness, and tearing. Transpore tape was applied to the right upper eyelid of
      each patient; the left eye was used as a control. A questionnaire was used to
      assess relief or persistence of the symptoms before, during, and after tape
      adhesion. RESULTS: Analysis of variance showed a significant difference between
      the study and control groups (P = .002). Tukey honestly significant difference
      analysis revealed a significant difference in symptoms before and during tape
      adhesion and a significant difference during and after tape adhesion. Symptoms in
      the control eye remained unchanged. CONCLUSION: Use of adhesive tape can be an
      effective temporary measure for relief of symptoms of inturned upper eyelid
      eyelashes.

PMID- 22652850
TI  - William Lawrence and the English ophthalmology textbooks of the 1830s and 1840s.
AB  - William Lawrence was a leading English ophthalmic surgeon in the middle of the
      19th century. This article briefly discusses his life, career, and well-known
      textbook (Treatise on Diseases of the Eye). His book and 3 others were the best
      known English texts on diseases of the eye of the 1830s and 1840s. The 3 others
      were William Mackenzie's Practical Treatise on Diseases of the Eye, Richard
      Middlemore's Treatise on the Diseases of the Eye and Its Appendages, and Thomas
      Wharton Jones' Manual of the Principles and Practice of Ophthalmic Medicine and
      Surgery.

PMID- 22652853
TI  - Interview with Stephen J. Ryan, MD, by George B. Bartley, MD.

PMID- 22652852
TI  - The physician workforce discussion revisited: the implications for ophthalmology.

PMID- 22652851
TI  - Global burden of visual impairment and blindness.

PMID- 22652854
TI  - Curvularia endophthalmitis following open globe injuries.

PMID- 22652856
TI  - Phototherapeutic keratectomy for treatment of long-term dye migration after
      corneal tattooing.

PMID- 22652857
TI  - Optical coherence tomography and autofluorescence findings in photic maculopathy
      secondary to distant lightning strike.

PMID- 22652858
TI  - Crystallization after intravitreous foscarnet injections.

PMID- 22652859
TI  - Scleritis associated with toxoplasmic retinochoroiditis.

PMID- 22652860
TI  - Unusual paraneoplastic cause of vision loss: combined paraneoplastic cone
      dystrophy and optic neuropathy.

PMID- 22652861
TI  - Orbital sarcoma in a young patient with Li-Fraumeni syndrome.

PMID- 22652862
TI  - Prognostic accuracy of the seventh edition vs sixth edition of the American Joint
      Committee on Cancer tumor classification for adenoid cystic carcinoma of the
      lacrimal gland.

PMID- 22652863
TI  - Complications of blepharoptosis surgery.

PMID- 22652864
TI  - Velocity map imaging of a slow beam of ammonia molecules inside a quadrupole
      guide.
AB  - Velocity map imaging inside an electrostatic quadrupole guide is demonstrated. By
      switching the voltages that are applied to the rods, the quadrupole can be used
      for guiding Stark decelerated molecules and for extracting the ions. The
      extraction field is homogeneous along the axis of the quadrupole, while it
      defocuses the ions in the direction perpendicular to both the axis of the
      quadrupole and the axis of the ion optics. To compensate for this astigmatism, a
      series of planar electrodes with horizontal and vertical slits is used. A
      velocity resolution of 35 m s(-1) is obtained. It is shown that signal due to
      thermal background can be eliminated, resulting in the detection of slow
      molecules with an increased signal-to-noise ratio. As an illustration of the
      resolving power we have used the velocity map imaging system to characterize the
      phase-space distribution of a Stark decelerated ammonia beam.

PMID- 22652865
TI  - Sleep in invertebrates: crayfish.
AB  - Although sleep is a very conspicuous behavior in all animals that we are
      frequently in contact with and possibly in many others, its scientific study was
      for many years restricted to very few of them. However, since the end of the XX
      century there have been studies about sleep in several animals and currently many
      of them attempt to found, first, if all animals sleep and second, if their sleep
      is similar to that of other animals. An important objective of this search is to
      identify the animal species in which sleep originated, which might gives us clues
      about the need that was fulfilled by such behavior. The search started with
      insects, among the most developed arthropods, but has now been expanded to
      include other invertebrates, among them crustaceans. In this work we review some
      aspects of sleep in invertebrates, focusing on the crustacean crayfish, animals
      in which both, behavioral and electrophysiological studies have been conducted
      and whose results show surprising similarities with sleep in mammals.

PMID- 22652866
TI  - Proteinase-activated receptors in the endometrium and endometriosis.
AB  - Proteinase-activated receptors (PARs) are G protein-coupled receptors activated
      by various proteinases. PARs play important roles in haemostasis, thrombosis, and
      inflammation. PAR1 and PAR2 are expressed in endometrial cells from the eutopic
      endometrium and endometriotic cells derived from endometriotic lesions. A typical
      activator of PAR1, thrombin, and a typical activator of PAR2, tryptase, are
      produced in the endometrium as well as endometriotic lesions. PAR1 activation in
      endometrial stromal cells induces production of vascular endothelial growth
      factor and matrix metalloproteinases, and increases activities of tissue-type and
      urokinase-type plasminogen activator. PAR2 activation in endometrial stromal
      cells stimulates interleukin (IL)-8 and stem cell factor production and
      proliferation of the cells. PAR1 activation in endometriotic stromal cells
      induces production of IL-8, monocyte chemotactic protein-1, and cyclooxygenase-2,
      and proliferation of the cells. PAR2 activation in endometriotic stromal cells
      increases secretion of IL-6 and IL-8, and the number of the cells. These findings
      indicate a wide range of function of PAR1 and PAR2 in the endometrium and
      endometriosis, and suggest PAR1 and PAR2 as possible therapeutic targets for
      endometriosis.

PMID- 22652867
TI  - The role of NF-kappaB in endometriosis.
AB  - The nuclear factor kappaB (NF-kappaB) is a ubiquitously expressed transcription
      factor playing vital roles in innate immunity and other processes involving
      cellular survival, proliferation, and differentiation. This review highlights the
      importance of NF-kappaB in the pathophysiology of endometriosis. Constitutive
      activation of NF-kappaB has been shown in endometriotic lesions. Complex
      interactions of NF-kappaB with steroid receptors and apoptotic molecules in
      endometriosis resulting in opposing roles of NF-kappaB are discussed. NF-kappaB
      regulates the expression of cytokines mediating autocrine self-amplifying cycles
      of cytokine release and NF-kappaB activation, leading to maintenance of
      inflammatory reactions in endometriosis. NF-kappaB can contribute to the
      increased ability of endometriotic cells to invade and adhere to the peritoneal
      surface by regulating the expression of matrix metaloproteinases. We are
      presenting the role of NF-kappaB to regulate vascularization and oxidative stress
      in endometriotic cells. Effects of drugs used for the treatment of endometriosis
      on NF-kappaB pathway are presented and we show how drugs that inhibit the NF
      kappaB can mediate the progression of endometriosis. Novel therapeutic strategies
      involving the NF-kappaB and applied in endometriosis are also discussed.

PMID- 22652868
TI  - Heterogeneity of cancer-initiating cells within glioblastoma.
AB  - Malignant gliomas, particularly glioblastoma multiforme (GBM), account for the
      majority of brain tumors. Their incidence is increasing world wide and they are
      incurable. Although a transient response to therapy is observed, tumor recurrence
      is inevitable and occurs within tissue that has received cytotoxic therapy. This
      suggests that a subpopulation of resistant cells is responsible for tumor
      regrowth. The treatment of GBMs represents a daunting challenge to clinicians due
      principally to the lack of effective therapeutic options. One explanation for
      this is the marked cellular and genetic heterogeneity within and across these
      types of tumors. Unravelling the cellular composition of gliomas and describing
      cell lineage relationships are essential for therapeutic breakthroughs. The
      recent proposal that a small percentage of cells with stem cells characteristics
      are responsible for tumor initiation and growth has sparked an interest in
      applying approaches used to study somatic stem cells toward an understanding of
      the cellular elements responsible for cancer progression and recurrence. To
      outline the relevance of these findings is the purpose of this review.

PMID- 22652869
TI  - Effect of additives on enzyme-catalyzed polymerization of phenols and aromatic
      amines.
AB  - Among biological approaches to the removal of aromatic amines and phenols from
      wastewater, the so-called enzyme-catalyzed polymerization and precipitation
      (ECPP) process relies on the use of oxidoreductases acting via radical mechanisms
      and characterized by a rather relaxed substrate specificity, such as laccase,
      tyrosinase and peroxidases. The main technical constraints of ECPP processes are
      due to a variety of enzyme deactivation phenomena occurring during catalysis and
      to the incomplete removal of oxidation products from solution. In order to put
      ECPP into practice, these drawbacks have to be either counteracted or minimized.
      Although several approaches, such as enzyme immobilization and reaction
      engineering, have been proposed to limit these constraints, this review is
      intended to provide a wide survey on some chemical additives with either
      protective or coagulating effects that have been so far employed for these
      purposes.

PMID- 22652870
TI  - Small RNA in spermatogenesis and male infertility.
AB  - Small RNA has become a crucial regulator of protein synthesis during
      spermatogenesis. Alterations in small RNA function prove to be detrimental to
      proper spermatogenesis. As many patients suffer from idiopathic infertility,
      understanding the molecular mechanisms of small RNA identifies possible causes of
      certain types of infertility. With a comprehensive review of the history of miRNA
      and piRNA function and specificity in the testis from a wide range of studies
      offers a view of detrimental defects of small RNA. By combining a concise
      overview of small RNA mechanism and recent research we explain how some cases of
      male infertility can be a product of complications in specific small RNA
      functions.  The future direction section offers insight into how infertility
      treatment may be approached with a novel perspective.

PMID- 22652871
TI  - Cell sources for cartilage repair; contribution of the mesenchymal perivascular
      niche.
AB  - Tissue and cell sources for cartilage repair are revised, including: 1) cartilage
      and subchondral bone (auto and allografts; single or multiple/mosaicplasty
      grafts), 2) cultured chondrocytes (autologous/ACI, characterized/CCI, matrix
      assisted/MAC, or allogenic), 3) adult mesenchymal stem cells (MSCs), 4)
      progenitor cells from perichondrium and periosteum, 5) embryonic and prenatal
      stem cells, 6) induced pluripotent stem cells, and 7) genetically modified cells.
      We consider the biological mechanisms that explain usage and possible
      complications, advantages and limitations, emerging technologies and possible
      modulations on extracellular matrix properties and on migration, proliferation,
      de-differentiation, re-differentiation, morphology, function and integration of
      the cells. The study of MSC role involve: a) identification, b) location
      (perivascular niche hypothesis, pericytes as progenitor cells), c) lineage
      (myoadipofibrogenic system: transit amplifying cells, fibroblast/myofibroblasts,
      chondrocytes, osteoblasts, odontoblasts, vascular smooth muscle cells and
      adipocytes), and d) use in cartilage repair, comprising: 1) MSCs recruited from
      neighbouring tissues (bone marrow stimulation, MSCs based "in situ" cartilage
      repair, microfracture) and 2) MSCs cultured and expanded from bone marrow,
      adipose tissue, synovial membrane or granulation tissue.

PMID- 22652872
TI  - Pharmacologic efficacy in inflammatory bowel disease models.
AB  - The utility of inflammatory bowel disease (IBD) models in evaluating
      pharmacologic efficacy of novel drug candidates is reviewed. IBD models are
      generally classified into six groups based on the etiopathogenesis: chemically-
      and hapten-induced, spontaneously developed, T-cells, transgenic and
      immunoregulatory knockout models. The chemically- and hapten-induced models are
      the most widely utilized for evaluating pharmacologic efficacy of novel drug
      candidates because they are technically simple and rapid to induce gut pathology.
      In contrast, the T-cells adoptive transfer model is technically more complex to
      execute with longer study duration, resulting in the rare utility of this model
      in pharmacologic efficacy studies. Spontaneously developed, transgenic and
      immunoregulatory knockout IBD models gradually develop spontaneous colitis or
      ileitis as they age. In this critical review, the pathological and immunological
      characteristics of various IBD animal models, and the pharmacologic efficacy of
      current therapeutic agents and drug candidates for IBD in these animal models are
      compared. Moreover, perspectives on experimental conditions, and applicability to
      evaluation of prophylactic and therapeutic pharmacologic efficacy of drug
      candidates in drug discovery and development are discussed.

PMID- 22652873
TI  - Environmental stress influencing plant development and flowering.
AB  - Plants are sessile organisms and unlike animals, cannot run away from adverse
      environmental conditions. Therefore, they have evolved sophisticated signaling
      and protective systems to overcome sub-lethal stress situations. Although, effect
      of stress on physiology and morphology were studied earlier, the research on
      molecular mechanisms of stress response is albeit new. Studies at the molecular
      level on stress physiology reveal that, many stress-induced pathways converge
      downstream or interact significantly. Abiotic stress factors regulate the extent
      and pattern of developmental programme. The timing of transition from vegetative
      to flowering phase, which is vital for survival and reproductive success, is
      often altered under various stresses. Unraveling the mechanisms by which
      different environmental stresses induce their effects and how tolerance to stress
      is achieved is an active area of research. Enhancing stress tolerance, especially
      in crop plants is an area of prime importance. In this review, we focus on stress
      responses induced by temperatures, high and low light intensities, UV radiation,
      drought and salinity stress and summarize the recent advancements by highlighting
      the underlying molecular pathways and processes.

PMID- 22652875
TI  - Computational methods for the analysis of tag sequences in metagenomics studies.
AB  - Metagenomics commonly refers to the study of genetic materials directly derived
      from environments without culturing. Several ongoing large-scale metagenomics
      projects related to human and marine life, as well as pedology studies, have
      generated enormous amounts of data, posing a key challenge for efficient
      analysis, as we try to 1) understand microbial organism assemblage under
      different conditions, 2) compare different communities, and 3) understand how
      microbial organisms associate with each other and the environment.To address such
      questions, investigators are using new sequencing technologies, including Sanger,
      Illumina Solexa, and Roche 454, to sequence either particular genes, called tag
      sequences, mostly 16S or 18S ribosomal RNA sequences or other conserved genes, or
      whole metagenome shotgun sequences of all the genetic materials in a given
      community. In this paper, we review computational methods used for the analysis
      of tag sequences.

PMID- 22652874
TI  - How HLA-DM works: recognition of MHC II conformational heterogeneity.
AB  - Helper T cells respond to peptide antigens derived from exogenous sources
      presented by MHC II on antigen presenting cells.  Antigens from pathogens are
      internalized by professional antigen presenting cells (APC) and processed for
      presentation.  Certain epitopes are selected during processing as the final
      peptides for stimulation of T cells and are termed "immunodominant".
      Understanding how selection of immunodominant epitopes takes place has been a
      difficult task because of the complexity of the mechanisms governing both antigen
      processing and T cell recognition.  In this review, we discuss our current
      understanding of HLA-DM function in peptide exchange and selection and its
      relevance to epitope immunodominance.

PMID- 22652876
TI  - Particle shape effects in vitro and in vivo.
AB  - Particles that have the potential to deliver imaging agents and drugs to cells
      and tissue now have many different shapes and sizes. This diversity in particle
      shape could provide new options for potential treatments of diseases because
      geometry affects biodistribution. However, the myriad of particle shapes now
      available increases the number of variables or parameters that must be taken into
      consideration for the drug delivery field to understand particle-cell
      interactions. This is especially true when the shape of a particle is a tunable
      parameter along with particle chemistry, charge, and hydrophobicity. Here we
      review the impact of shape on particle-cell interactions in vitro and the
      ramifications of different particle geometries on circulation, biodistribution,
      localization to tumors, and toxicology in rodents.

PMID- 22652878
TI  - A switch in aminergic modulation of locomotor CPG output during amphibian
      metamorphosis.
AB  - In the South African clawed frog, Xenopus laevis, a complete functional switch in
      the mode of locomotion occurs during development from axial, undulatory, tail
      based swimming in post-hatching tadpoles to limb-based kick propulsion in the
      adult froglet. At key stages during the metamorphosis from tadpole to frog both
      locomotor systems are present, co-functional and subject to modulation by the two
      ubiquitous biogenic amines, serotonin (5-HT) and noradrenaline (NA), arising from
      the brainstem. Here we review evidence on the roles of 5-HT and NA in the early
      maturation and dynamic modulation of spinal locomotor circuitry in the
      postembryonic tadpole and describe the way in which the modulatory effects of the
      two amines, which are always in opposition, subsequently switch during the
      metamorphic period of development. We speculate on the underlying cellular,
      synaptic and network mechanisms that might be responsible for this change in
      role.

PMID- 22652879
TI  - Antimicrobial peptides in the brain: neuropeptides and amyloid.
AB  - Antimicrobial peptides (AMPs) are ancient defense molecules of the innate immune
      system. Similarly, neuropeptides are ancient signaling molecules. Similarities in
      size, cationic charge or amphipatic design between some neuropeptides and AMPs
      suggest that they might serve an additional function in antimicrobial immunity.
      This hypothesis, supported by experimental evidence, adds another level of
      understanding to the intricate crosstalk between the nervous system and the
      immune system. The recent observation, that another brain protein, amyloid-beta,
      has antimicrobial activities, suggests that this peptide, prominently known as an
      accumulating toxic waste material, might have a physiologic function as anti
      infective agent.

PMID- 22652877
TI  - Autophagy: mechanism and physiological relevance 'brewed' from yeast studies.
AB  - Autophagy is a highly conserved process of quality control occurring inside cells
      by which cytoplasmic material can be degraded and the products recycled for use
      as new building blocks or for energy production. The rapid progress and
      'explosion' of knowledge concerning autophagic processes in mammals/humans that
      has occurred over the last 15 years was driven by fundamental studies in yeast,
      principally using Saccharomyces cerevisiae, leading to the identification and
      cloning of genes required for autophagy. This chapter reviews the role of yeast
      studies in understanding the molecular mechanisms of autophagic processes,
      focusing on aspects that are conserved in mammals/humans and how autophagy is
      increasingly implicated in the pathogenesis of disease and is required for
      development and differentiation.

PMID- 22652880
TI  - Peptides: an arrival point in cancer vaccinology.
AB  - During the past few decades, numerous approaches towards therapeutic vaccines
      have been investigated. In addition to traditional prophylactic vaccines against
      infectious microorganisms, there have been attempts to develop therapeutic
      vaccines for indications as complex as autoimmunity and cancer. Driven by an
      increasing understanding of the underlying mechanisms, researchers have attempted
      to interfere with complex molecular cascades during disease progression.
      Monoclonal antibodies have gained more importance, and their specificity has
      become more predictable. However, in spite of the advances in our knowledge,
      crucial problems linger unsolved in vaccinology, such as the major
      histocompatibility complex (MHC) degeneration phenomenon, the escape from immune
      surveillance of cancer and microbes, and the possibility of adverse events,
      perhaps linked to peptide cross-reactivity. In essence, it seems that in order to
      understand immune responses the peptide-peptide interactions have yet to be
      clearly defined. These issues will be discussed in the frame of current
      approaches to vaccine development with special focus on cancer vaccines.

PMID- 22652881
TI  - Peptide cross-reactivity: the original sin of vaccines.
AB  - Recent numerous studies have demonstrated that an extensive peptide identity
      platform characterizes entities spanning the entire evolutionary arc from viruses
      to humans and establishes an immune cross-reactivity potential among viruses and
      bacteria, as well as between microbial organisms and humans. This peptide
      commonality presents obstacles to diagnostics, burdens therapeutic vaccinology
      with harmful collateral effects, and can result in autoimmune diseases. The
      present study 1) recapitulates the significance of cross-reactivity from the
      molecular mimicry hypothesis to the phenomenon of microbial immunoevasion; 2)
      analyzes the implications of cross-reactivity for the self-nonself discrimination
      issue; 3) highlights the negative role exerted by cross-reactions in translating
      immunology to effective vaccines; 4) outlines the  vicious circle connecting
      peptide commonality, microbial immune escape, adjuvanted vaccines and autoimmune
      cross-reactions; and 5) conclusively indicates sequence uniqueness as a basic
      criterion for designing effective vaccines exempt from autoimmune cross
      reactions.

PMID- 22652882
TI  - Manipulation of microglial activity as a therapy for Alzheimer's disease.
AB  - The review aims to elucidate the potential of microglia as a therapeutic target
      in alleviating Alzheimer's Disease (AD). Microglia are the resident immune cells
      in the brain which respond to the presence of the hallmarks of AD, amyloid-beta
      (A beta) plaques and neurofibrillary tangles (NFT). Activated microglia are able
      to phagocytose and secrete pro-inflammatory and anti-inflammatory cytokines.
      However, the eventual accumulation of excess A beta peptides and NFT in AD means
      that microglial clearance of pathogens has been impaired. Pro-inflammatory
      cytokines may also contribute to the neurodegeneration. Based on the amyloid
      cascade hypothesis, A beta-activated microglia can produce pro-inflammatory
      cytokines which may exacerbate the hyperphosporylation of tau proteins that forms
      NFT in AD pathology. Microglial activation can thus be manipulated to prevent
      neurodegeneration and promote neuroprotection through several therapeutic agents
      and methods.  Further studies regarding comprehensive microglial response towards
      A beta and NFT are required to develop an effective treatment of AD involving
      microglia.

PMID- 22652883
TI  - Cardiomyocyte generation using stem cells and directly reprogrammed cells.
AB  - Cardiomyocytes are terminally differentiated cells with limited regenerative
      capacity in the adult heart, making cell replacement therapy an attractive option
      to repair injured hearts. Embryonic stem (ES) cells and induced pluripotent stem
      (iPS) cells are pluripotent and capable of infinite expansion in vitro,
      implicating them as ideal cell types for cell replacement therapy. During the
      past several years, significant advances in iPS cell generation technology,
      cardiac differentiation, and cell purification protocols were achieved for the
      development of stem cell-based heart therapies. The discovery of iPS cells has
      also sparked the novel idea of direct conversion of mature cell types into
      another cell type without passing through a pluripotent stem cell state.
      Functional cardiomyocytes could therefore be directly reprogrammed from
      differentiated somatic cells by transduction of the three cardiac transcription
      factors, Gata4, Mef2c, and Tbx5. Herein, we review the recent research
      achievements and discuss future challenges in stem cell-based cardiac generation
      and direct cardiac reprogramming technology for heart regeneration.

PMID- 22652884
TI  - The malaria digestive vacuole.
AB  - During the development of malaria parasites within human erythrocytes, the fusion
      of digestive vesicles gives rise to a large digestive vacuole (DV). This
      organelle, which is maintained at low pH, processes 60-80 percent of the
      erythrocyte hemoglobin to provide a pool of amino acids that is crucial for
      parasite growth and development.  During proteolysis, heme is released from
      hemoglobin as a toxic byproduct and is detoxified by biocrystallization to
      hemozoin.  Proteases that contribute to hemoglobin breakdown, as well as other DV
      associated proteins, arrive at this site via several different transport
      pathways. Antimalarial quinoline drugs, such as chloroquine, act by binding to
      heme and thus prevent its sequestration into hemozoin.  Other drugs, such as
      artemisinin, may cause oxidative damage of DV macromolecules and membranes. The
      membrane of the DV contains ion pumps and transporters that maintain its low pH
      but are also pivotal in the development of parasite resistance to several
      antimalarial drugs.  Methods for the isolation of the DV organelle have been
      developed to study the biogenesis and function of this important organelle.

PMID- 22652885
TI  - Receptor-associated prorenin system in the pathogenesis of retinal diseases.
AB  - Receptor-associated prorenin system (RAPS) refers to the pathogenic mechanisms
      whereby prorenin binding to (pro)renin receptor [(P)RR] dually activates tissue
      renin-angiotensin system (RAS) and RAS-independent intracellular signaling
      through the receptor. Although we found significant involvement of angiotensin II
      type 1 receptor (AT1-R) in intraocular inflammation and neovascularization,
      central pathologies of age-related macular degeneration and diabetic retinopathy,
      the association of RAPS with these vision-threatening disorders has not been
      defined. (P)RR blockade to murine disease models led to significant suppression
      of laser-induced choroidal neovascularization and diabetes-induced retinal
      inflammation together with the upregulation of intercellular adhesion molecule
      (ICAM)-1, monocyte chemotactic protein (MCP)-1 and vascular endothelial growth
      factor (VEGF). Either the genetic ablation or the pharmacological blockade of AT1
      R exhibited significant reduction of choroidal and retinal abnormalities, both of
      which were further suppressed by (P)RR blockade. (P)RR blockade inhibited ERK
      activation and the production of VEGF and MCP-1, but not ICAM-1, in AT1-R
      deficient mice with retinal and choroidal disorders. These recent findings
      indicate significant contribution of RAPS to the pathogenesis of age-related
      macular degeneration and diabetic retinopathy.

PMID- 22652886
TI  - Single molecular level analysis and processing in nanochannels.
AB  - Recent advances in nanofluidic technologies have enabled devices to be fabricated
      that integrate nanochannels with at least one dimension smaller than several
      hundred nanometers. Since this dimension is close to the sizes of biomolecules
      such as DNA, proteins, and other biomolecules, it opens up new scientific and
      technological fields based on analysis and manipulation of single molecules. This
      paper reviews the current state of knowledge regarding single molecular level
      analysis and processing in nanochannels, particularly experimental findings in
      this area. While there have been many theoretical and molecular simulation
      studies, this paper surveys experimental studies. Following a brief survey of
      techniques for fabricating nanochannels, we review fundamental studies of single
      molecule behavior and manipulation in nanochannels. We then discuss important
      transport phenomena of single molecules in nanochannels. Finally, the emerging
      challenge of electrical single-molecule detection and its possible applications
      are highlighted.

PMID- 22652888
TI  - Growth factor pathways in development and progression of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma accounts for approximately 700,000 deaths per year. 
      This tumor displays morphologic and phenotypic heterogeneity, and heterogeneity
      extends to the molecular level.  Nevertheless, common pathways have been
      identified that are variably employed by these tumors. Such pathways often
      include aberrant signaling by growth factors, many of which are involved in liver
      development and regeneration. This review focuses on several such pathways and
      highlights patterns of structural expression of relevant molecules as well as
      effects of pathway stimulation or inhibition, both in vitro and in vivo. 
      Specifically, the HGF/MET axis, epidermal growth factor receptors and associated
      ligands, insulin growth factor, vascular endothelial growth factor, fibroblast
      growth factor, platelet-derived growth factor and TGF-beta pathways are reviewed
      in the context of experimental models of HCC. Clinical-pathologic correlations
      are drawn for each of these, and current status of molecular targeted therapies
      is assessed.  Review of available information indicates that redundancies and
      interactions among these signaling pathways must be taken into account if they
      are to be exploited to block and reverse HCC growth and spread.

PMID- 22652887
TI  - Developmental regulation of decidual cell polyploidy at the site of implantation.
AB  - Polyploidy has been reported in several animal cells, as well as within humans;
      however the mechanism of developmental regulation of this process remains poorly
      understood. Polyploidy occurs in normal biologic processes as well as in
      pathologic states. Decidual polyploid cells are terminally differentiated cells
      with a critical role in continued uterine development during embryo implantation
      and growth.  Here we review the mechanisms involved in polyploidy cell formation
      in normal developmental processes, with focus on known regulatory aspects in
      decidual cells.

PMID- 22652889
TI  - Endogenous anticancer mechanism: differentiation.
AB  - It has been recently shown that within heterogeneous tumor masses a small
      population of less differentiated transformed cells has the ability to self-renew
      and regenerate the bulk of the tumor. Their similarities with normal stem cells
      in terms of gene expression patterns, proliferative capacity and surface markers
      rendered them the name of cancer stem-like cells (CSC), and these are thought to
      be the tumor initiating cells (TIC). Their limited susceptibility to classical
      anti-tumor therapy help explain the high incidence of cancer-treatment relapses
      observed in selected malignancies. Much effort is being directed towards the
      understanding of factors that maintain CSC survival and their self-renewal
      capacity, with the goal that these same signaling pathways can be harnessed for
      treatments that aim at inducing CSC differentiation. This review will discuss the
      CSC theory, its implications, potential signaling pathways responsible for
      maintaining their undifferentiated and pluripotent states, and new venues being
      explored to target these cells in modern cancer therapy.

PMID- 22652890
TI  - Cytochrome P450 in non-small cell lung cancer related to exogenous chemical
      metabolism.
AB  - The occurrence of lung cancer is associated with smoking, which exposes smokers
      to a series of carcinogenic chemicals. CYP (cytochrome P450) usually metabolizes
      carcinogens to their inactive derivatives, but occasionally convert the chemicals
      to more potent carcinogens. In addition to the metabolism of carcinogenic
      compounds, CYP also participates in the activation and/or inactivation of anti
      carcinogenic agents, suggesting that the local CYP expression in lung cancer and
      surrounding tissues could be an important determinant of efficacy of anticancer
      drugs. Furthermore, CYP19 (aromatase), estrogen synthase P450, expressed in more
      than 80 percent of non-small cell lung cancers. It suggests an association
      between estrogens and cancer development, which makes aromatase an attractive
      therapeutic target for the treatment of lung cancer. 1alpha,25-Dihydroxyvitamin
      D3 has an inhibitory effect on the proliferation of cancer tissues, and is
      converted to its inactive 24-hydroxylated derivatives by CYP24, which is
      frequently expressed in lung cancer tissues. Therefore, understanding the CYP
      expression in tumor tissues is important in developing better therapies for lung
      cancer, and may lead us to standardized, tailor-made therapies for individuals.

PMID- 22652891
TI  - Unaffected motor endplate occupancy in eye muscles of ALS G93A mouse model.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative
      disorder characterised by selective loss of motor neurons with accompanying
      muscle paralysis and respiratory failure. Despite progressive paralysis in trunk
      and extremity muscles, disturbed eye motility is not a hallmark of ALS.
      Extraocular muscles (EOMs) of terminal ALS patients show far less morphological
      signs of disease than their limb muscles. One of the earliest signs of the
      disease in the transgenic G93A SOD1 mouse model of ALS is loss of motor neuron
      contact at the neuromuscular junctions (NMJ) in limb muscles. We used
      immunohistochemistry to identify NMJs and evaluate innervation in EOMs and limb
      muscles of G93A mice. In G93A limb muscles, loss of axonal contact was seen in 6
      82 percent of the NMJs. On the contrary, the degree of endplate occupancy in the
      EOMs did not differ between transgenic mice and wild-type controls. We propose
      that EOM-specific properties make these muscles more resistant to the underlying
      pathophysiological process of ALS and that the EOMs are a useful model to advance
      our understanding of ALS.

PMID- 22652892
TI  - Transcriptomic analysis reveals pH-responsive antioxidant gene networks.
AB  - Reactive oxygen species (ROS) are produced in different physiological conditions.
      In response to ROS imbalance cells activate oxidative stress defenses, which
      include more than 60 antioxidant genes. It has been suggested that gene products
      associated with ROS detoxification can work coordinately, acting as an
      antioxidant-defense network. However, the functional overlap among oxidative
      stress defenses and other related cell functions makes difficult the
      characterization of this network. We previously described a network-based model
      to characterize the interactions existing among different antioxidant gene
      products and their substrates. Here, we test whether this network-based model of
      human antioxidant genes can respond to different physiological conditions. We
      used a systems biology approach applied to the analysis of two independent gene
      expression datasets: transcriptomes from HeLa cells and primary astrocytes
      maintained under hypoxic conditions and transcriptomes from SKGT4 cells exposed
      to low pH environment. We found that the proposed gene network model responds
      selectively to both hypoxia and acidosis. We anticipate that this antioxidant
      gene network model can be helpful to describe stress-responsive expression
      profiles in different cell types.

PMID- 22652893
TI  - Role of NK cells and HLA-G in endometriosis.
AB  - Impaired natural killer (NK) activity in women with endometriosis is thought to
      promote implantation and progression of endometrial tissue, in accord with
      Sampson's hypothesis. However, the mechanisms responsible for decreased NK cell
      activity and the antigens recognized by NK cells are not clear.We focused on
      human leukocyte antigen (HLA)-G, a ligand of NK receptors, expression and its
      menstrual cycle changes by eutopic endometrium. Interestingly, HLA-G expression
      was identified on eutopic endometrium only in the menstrual phase but not in the
      proliferative or secretory phases. Furthermore, HLA-G expressing cells were also
      detected in peritoneal fluid during the menstrual period. During retrograde
      menstruation, HLA-G expressing endometrial tissue may enter the peritoneal
      cavity, and may be reduced by immunosurveillance system. Although peritoneal NK
      cells play an important role in this system, impairment of NK cytotoxicity via
      HLA-G may allow peritoneal endometrial cell survival and implantation. In this
      review, we discuss the pathogenesis of endometriosis from the viewpoint of
      intraperitoneal immune interaction between NK cell receptors and HLA-G that can
      enter into peritoneal cavity from eutopic endometrium through retrograde
      menstruation.

PMID- 22652894
TI  - The actin-like MreB proteins in Bacillus subtilis: a new turn.
AB  - A decade ago, two breakthrough descriptions were reported: 1) the first helix
      like protein localization pattern of MreB and its paralog Mbl in Bacillus
      subtilis and 2) the crystal structure of Thermotoga maritima MreB1, which was
      remarkably similar to that of actin. These discoveries strongly stimulated the
      field of bacterial development, leading to the identification of many new
      cytoskeletal proteins (1) and the publication of many studies describing the
      helical patterns of protein, DNA and even lipid domains. However, today, new
      breakthroughs are shaking up what had become a dogma. Instead of helical
      structures, MreBs appear to form discrete patches that move circumferentially
      around the cell, questioning the idea of MreB cables forming an actin-like
      cytoskeleton. Furthermore, increasing evidence of biochemical properties that are
      unlike the properties of actin suggest that the molecular behavior of MreB
      proteins may be different. The aim of this review is to summarize the current
      knowledge of the so-called "actin-like" MreB cytoskeleton through a discussion of
      the model Gram-positive bacterium B. subtilis and the most recent findings in
      this rapidly evolving research field.

PMID- 22652895
TI  - Impact of perioperative bleeding on the protective effect of beta-blockers during
      infrarenal aortic reconstruction.
AB  - BACKGROUND: The use of beta-blockers during the perioperative period remains
      controversial. Although some studies have demonstrated their protective effects
      regarding postoperative cardiac complications, others have demonstrated increased
      mortality when beta-blockers were introduced before surgery. METHODS: In this
      observational study involving 1,801 patients undergoing aortic reconstruction, we
      prospectively assessed beta-blocker therapy compared with no beta-blocker
      therapy, with regard to cardiac and noncardiac postoperative outcomes using a
      propensity score approach. The impact of beta-blockers was analyzed according to
      the intraoperative bleeding estimated by transfusion requirements. RESULTS: In
      hospital mortality was 2.5% (n=45), beta-blocker use was associated with a
      reduced frequency of postoperative myocardial infarction (OR=0.46, 95% CI [0.26;
      0.80]) and myocardial necrosis (OR=0.62, 95% CI [0.43; 0.88]) in all patients,
      but also with an increased frequency of multiple organ dysfunction syndromes
      (OR=2.78, 95% CI [1.71; 4.61]). In patients with severe bleeding (n=163; 9.1%),
      the frequency of in-hospital death (OR=6.65, 95% CI [1.09; 129]) and/or multiple
      organ dysfunction syndromes (OR=4.18, 95% CI [1.81; 10.38]) were markedly
      increased. Furthermore, no more than 28% of the patients who died presented with
      postoperative myocardial infarction, whereas 69% of the patient with a
      postoperative myocardial infarction also presented an excessive bleeding.
      CONCLUSIONS: Perioperative beta-blocker therapy was associated with an overall
      reduction in postoperative cardiac events. In the vast majority of patients with
      low perioperative bleeding, the global effect of beta-blockers was protective; in
      contrast, patients given beta-blockers who experienced severe bleeding had higher
      mortality and an increased frequency of multiorgan dysfunction syndrome.

PMID- 22652897
TI  - Chronic pain as a narratological distress: a phenomenological study.
AB  - OBJECTIVES: This paper reports finding from a study that focused on people living
      with chronic pain, chronicling their experiences of pain and emotional distress,
      and their social and personal narratives. METHODS: The paper presents an
      interpretative phenomenological analysis (IPA) of six interviews conducted with
      men and women aged between 27 and 61. The interviews were taken from a larger
      study of the experience of chronic pain. FINDINGS: Chronic pain is a double faced
      phenomenon: a vivid and total experience on one hand, an elusive and deceptive
      phenomenon on the other. The nature of this phenomenon - together with the
      medical and public discourse that ignores and delegitimizes chronic pain this
      condition - prompts people to question their own experiences and to face what we
      define as a narratological distress. DISCUSSION: Narratological distress is the
      internal battle between two unwanted narratives: The elusive delegitimizing
      narrative of denial, which seeks to ignore the experience of pain; and the
      narrative that acknowledges the pain, but with the price of accepting oneself as
      "ill" or "disabled."

PMID- 22652896
TI  - Asymmetric dimethylarginine reduces nitric oxide donor-mediated dilation of
      arterioles by activating the vascular renin-angiotensin system and reactive
      oxygen species.
AB  - INTRODUCTION: We tested the hypothesis that asymmetric dimethylarginine (ADMA)
      interferes with other mechanisms in addition to inhibition of nitric oxide
      synthase (NOS). Thus, in skeletal muscle arterioles, in the presence of ADMA, we
      investigated the dilator effect of an NO donor and increases in flow and aimed to
      elucidate the underlying mechanisms, including the role of oxidative stress,
      which is known to reduce the bioavailability of NO. METHODS AND RESULTS: In
      isolated rat gracilis skeletal muscle arterioles (~160 um at 80 mm Hg), ADMA
      (similarly to pyrogallol) reduced dilations to sodium nitroprusside (SNP), which
      was significantly prevented by the presence of superoxide dismutase (SOD) and
      catalase (CAT): SNP 10(-8)M; control: 43.2 +/- 3%, ADMA: 4.9 +/- 1%, ADMA +
      SOD/CAT: 30.2 +/- 9% (p < 0.05). Also, ADMA reduced basal diameter and flow
      induced dilations, which were not restored by L-arginine, but prevented by
      SOD/CAT and by inhibition of NAD(P)H oxidase (but not xanthine oxidase) and by an
      angiotensin-converting enzyme inhibitor or an angiotensin type 1 receptor blocker
      (ARB). ADMA increased the production of reactive oxygen species detected by
      lucigenin-enhanced chemiluminescence, which was significantly inhibited by SNP or
      ARB. CONCLUSION: We suggest that by activating the vascular renin-angiotensin
      NAD(P)H oxidase pathway, ADMA elicits oxidative stress, which interferes with the
      bioavailability of NO and consequently reduces NO-mediated dilations.

PMID- 22652898
TI  - Role of regucalcin in brain calcium signaling: involvement in aging.
AB  - Regucalcin was discovered in 1978 to be a calcium-binding protein that does not
      contain the EF-hand motif of the calcium-binding domain [M. Yamaguchi and T.
      Yamamoto, Chem. Pharm. Bull., 26, 1915-1918, 1978]. The regucalcin gene is
      localized on the X chromosome and its expression is enhanced through various
      transcription factors. Regucalcin is known to play a multifunctional role as a
      suppressor protein of cell signaling in many cell types. Regucalcin is expressed
      in rat brain neurons and it is decreased in the cerebral cortex and hippocampus
      of the brain with aging. Neuronal Ca(2+) signaling has been implicated in
      mechanisms of neuronal plasticity like long-term potentiation, which is likely to
      play an important role in learning and memory. The disturbance of brain Ca(2+)
      homeostasis may play a pivotal role in the revelation of brain disease. The
      intracellular Ca(2+) in brain tissues is increased with aging. Aging enhances the
      entry of Ca(2+) into brain neuronal cells across the plasma membranes. An
      increase in the brain microsomal Ca(2+)-ATPase activity of rats with aging
      resulted in calcium accumulation in the microsomes of the Ca(2+)-sequestrating
      system that is partly related to the brain toxicity by calcium. Regucalcin had an
      inhibitory effect on rat brain microsomal Ca(2+)-ATPase activity. The suppressive
      effect of regucalcin on brain microsomal Ca(2+)-ATPase activity was weakened in
      aged rats. Regucalcin was found to inhibit brain cytosolic protein kinase C.
      Brain microsomal Ca(2+)-ATPase activity was enhanced by protein kinase C in aged
      rats. Regucalcin could also inhibit activity of Ca(2+)/calmodulin-dependent
      protein kinase, protein phosphatase, and Ca(2+)/calmodulin-dependent nitric oxide
      synthase, which is linked to Ca(2+) signaling, in the cytosol of rat brain
      neurons. These inhibitory effects of regucalcin were weakened with aging.
      Regucalcin may play a pivotal role in the regulation of Ca(2+) signaling which is
      stimulated through a neurotransmitter in the brain neurons with aging.

PMID- 22652899
TI  - Current transport across the pentacene/CVD-grown graphene interface for diode
      applications.
AB  - We investigate the electronic transport properties across the pentacene/graphene
      interface. Current transport across the pentacene/graphene interface is found to
      be strikingly different from transport across pentacene/HOPG and pentacene/Cu
      interfaces. At low voltages, diodes using graphene as a bottom electrode display
      Poole-Frenkel emission, while diodes with HOPG and Cu electrodes are dominated by
      thermionic emission. At high voltages conduction is dominated by Poole-Frenkel
      emission for all three junctions. We propose that current across these interfaces
      can be accurately modeled by a combination of thermionic and Poole-Frenkel
      emission. Results presented not only suggest that graphene provides low resistive
      contacts to pentacene where a flat-laying orientation of pentacene and
      transparent metal electrodes are desired but also provides further understanding
      of the physics at the organic semiconductor/graphene interface.

PMID- 22652900
TI  - Adrenocortical hormonal activity in 20-year-old subjects born small or
      appropriate for gestational age.
AB  - BACKGROUND: Altered adrenocortical activity is one suggested mechanism relating
      small birth size with the metabolic syndrome in adulthood. Adrenal androgen
      concentrations are higher in children born small (SGA) than appropriate for
      gestational age (AGA). AIM: To compare adrenocortical hormonal activity between
      20-year-old subjects born SGA or AGA. METHODS: Seventy 20-year-old subjects (35
      SGA and 35 age- and gender-matched AGA controls) were studied. Serum cortisol,
      cortisone, corticosteroid-binding globulin (CBG), glucocorticoid bioactivity
      (GBA), aldosterone, dehydroepiandrosterone sulfate (DHEAS) and androstenedione
      were measured, and the free cortisol index (FCI) was calculated. RESULTS: The
      mean levels of glucocorticoid parameters, aldosterone, DHEAS or androstenedione
      did not differ between the SGA and AGA groups. In both groups, the males had
      lower cortisol (p < 0.05) and CBG levels (p < 0.01) and higher DHEAS (p < 0.01)
      concentrations than the females. Females who used hormonal contraceptives had
      higher cortisol and CBG levels (p < 0.01) but similar FCI, GBA and DHEAS levels
      than females who did not use contraceptives. CONCLUSION: No differences in
      adrenocortical activity were found between 20-year-old SGA and AGA subjects.
      Enhanced peripubertal adrenal androgen secretion seems to disappear by early
      adulthood in full-term born SGA subjects. FCI and GBA are useful parameters in
      the evaluation of the glucocorticoid milieu during hormonal contraceptive use.

PMID- 22652902
TI  - Topical and systemic therapies for nickel allergy.
AB  - Nickel allergy can result in both cutaneous and systemic manifestations, and can
      range from mild to severe symptoms. A severe form of this allergy is the Systemic
      nickel allergy syndrome, clinically characterized by cutaneous manifestions
      (contact dermatitis, pompholyx, hand dermatitis dyshydrosis, urticaria) with
      chronic course and systemic symptoms (headache, asthenia, itching, and
      gastrointestinal disorders related to histopathological alterations of
      gastrointestinal mucosa, borderline with celiac disease). This review aims to
      briefly update the reader on past and current therapies for nickel contact
      allergy.

PMID- 22652903
TI  - Patch testing with a large series of metal allergens: findings from more than
      1,000 patients in one decade at Mayo Clinic.
AB  - BACKGROUND: The standard allergen series used in patch testing contains metals
      that most commonly cause allergic contact dermatitis, but testing with additional
      metal allergens is warranted for select patients. OBJECTIVE: To report our
      experience with patch testing of metals. METHODS: We retrospectively analyzed
      outcomes of 1,112 patients suspected of having metal allergies. Patients were
      seen from January 1, 2000, through December 31, 2009. Patch testing was performed
      with 42 metal preparations (6 in the standard series, 36 in the metal series).
      RESULTS: Patch testing most commonly was performed for patients with oral disease
      (almost half the patients), hand dermatitis, generalized dermatitis, and
      dermatitis affecting the lips, legs, arms, trunk, or face. At least one positive
      reaction was reported for 633 patients (57%). Metals with the highest allergic
      patch-test reaction rates were nickel, gold, manganese, palladium, cobalt,
      Ticonium, mercury, beryllium, chromium, and silver. Metals causing no allergic
      patch-test reactions were titanium, Vitallium, and aluminum powder. Metals with
      extremely low rates of allergic patch-test reactions included zinc, ferric
      chloride, and tin. Reaction rates varied depending on metal salt, concentration,
      and timing of readings. CONCLUSION: Many metals not in the standard series were
      associated with allergic patch-test reactions. The many questions raised by these
      findings, concerning patch testing with individual metals, will be the subject of
      future studies.

PMID- 22652905
TI  - Unusual localization of cell phone dermatitis.

PMID- 22652904
TI  - Phthalates in baby skin care products.
AB  - BACKGROUND: The systemic toxicity of phthalates has been extensively reported.
      Although rarely sensitizing, phthalates have been implicated in promoting the
      development of both atopy and contact dermatitis in animal models. Dermal
      absorption of phthalates may contribute to overall chemical burden. Infants may
      be particularly susceptible to chemical exposures. Baby skin care products may be
      a significant source of phthalate exposure. OBJECTIVE: We measured the phthalate
      content of 30 skin care products intended for babies and children. METHODS:
      Nineteen leave-on and 11 wash-off baby skin care products were analyzed for 17
      unique phthalates by an independent laboratory using standard gas chromatographic
      mass spectrometry. RESULTS: Of 30 products tested, four had phthalate levels
      above the reporting limit (0.1-0.5 ppm); of these, only one had levels above 1
      ppm (44 ppm). There was no statistical significance of phthalate detection in
      leave-on versus wash-off products (p = .578). CONCLUSION: The majority (26 of 30)
      of the baby skin care products analyzed did not have detectable phthalate levels.
      Four products had detectable phthalate levels. In baby skin care products, levels
      of the 17 phthalates tested are low overall, but occasional products may contain
      higher phthalate levels. Monitoring products to ensure safety standards are met
      may be warranted.

PMID- 22652906
TI  - Nonpruritic contact dermatitis from disperse blue dyes.

PMID- 22652907
TI  - In-lab three-dimensional printing: an inexpensive tool for experimentation and
      visualization for the field of organogenesis.
AB  - The development of the microscope in 1590 by Zacharias Janssenby and Hans
      Lippershey gave the world a new way of visualizing details of morphogenesis and
      development. More recent improvements in this technology including confocal
      microscopy, scanning electron microscopy (SEM) and optical projection tomography
      (OPT) have enhanced the quality of the resultant image. These technologies also
      allow a representation to be made of a developing tissue's three-dimensional (3
      D) form. With all these techniques however, the image is delivered on a flat two
      dimensional (2-D) screen. 3-D printing represents an exciting potential to
      reproduce the image not simply on a flat screen, but in a physical, palpable
      three-dimensional structure. Here we explore the scope that this holds for
      exploring and interacting with the structure of a developing organ in an entirely
      novel way. As well as being useful for visualization, 3-D printers are capable of
      rapidly and cost-effectively producing custom-made structures for use within the
      laboratory. We here describe the advantages of producing hardware for a tissue
      culture system using an inexpensive in-lab printer.

PMID- 22652909
TI  - APEX1 regulation of aldosterone synthase gene transcription is disrupted by a
      common polymorphism in humans.
AB  - RATIONALE: The genetic mechanisms underlying hypertension are unclear, but
      relative aldosterone excess, present in ~10% of hypertensive patients, is known
      to be a heritable trait. This phenotype associates with a T/C single nucleotide
      polymorphism (SNP) at position -344 of the aldosterone synthase gene (CYP11B2).
      However, deletion of this SNP has no effect on gene transcription. We have
      identified another T/C SNP at -1651, in tight linkage disequilibrium with the 
      344 SNP and here investigate its functional effect on CYP11B2 transcription.
      OBJECTIVE: We assessed the effect on transcriptional activity of the -1651 T/C
      SNP in vivo and in vitro and propose the mechanism by which transcriptional
      activity is altered. METHODS AND RESULTS: We demonstrated that the SNP at -1651
      exerts significant allele-dependent effects on CYP11B2 transcription. We confirm
      binding of the transcriptional repressor APEX1 to -1651T, which is associated
      with reduced transcriptional activity in relation to the less strongly bound 
      1651C. We show that inhibiting APEX1 by small molecule inhibition or small
      interfering RNA (SiRNA) leads to increased CYP11B2 transcription. In addition,
      overexpression of APEX1 is associated with reduced transcriptional activity.
      Finally, we also show that -1651T associates with lower excretion rates of
      aldosterone metabolites in human subjects. CONCLUSIONS: We conclude that APEX1 is
      a novel transcriptional repressor of CYP11B2 and that differential APEX1 binding
      at -1651 of CYP11B2 results in altered gene expression. This mechanism may
      contribute to the observed relationship between CYP11B2 genotype and aldosterone
      phenotype in a subgroup of hypertensive patients.

PMID- 22652917
TI  - Effects of an off-season conditioning program on the physical characteristics of
      adolescent rugby union players.
AB  - The aims of the study were to determine if a supervised off-season conditioning
      program enhanced gains in physical characteristics compared with the same program
      performed in an unsupervised manner and to establish the persistence of the
      physical changes after a 6-month unsupervised competition period. Forty-four
      provincial representative adolescent rugby union players (age, mean +/- SD, 15.3
      +/- 1.3 years) participated in a 15-week off-season conditioning program either
      under supervision from an experienced strength and conditioning coach or
      unsupervised. Measures of body composition, strength, vertical jump, speed, and
      anaerobic and aerobic running performance were taken, before, immediately after,
      and 6 months after the conditioning. Post conditioning program the supervised
      group had greater improvements in all strength measures than the unsupervised
      group, with small, moderate and large differences between the groups?x{2019}
      changes for chin-ups (9.1%; +/- 11.6%), bench-press (16.9%; +/- 11.7%) and box
      squat (50.4%; +/- 20.9%) estimated 1RM respectively. Both groups showed trivial
      increases in mass; however increases in fat free mass were small and trivial for
      supervised and unsupervised players respectively. Strength declined in the
      supervised group while the unsupervised group had small increases during the
      competition phase, resulting in only a small difference between the long-term
      changes in box-squat 1RM (15.9%; +/- 13.2%). The supervised group had further
      small increases in fat free mass resulting in a small difference (2.4%; +/- 2.7%)
      in the long-term changes. The postconditioning differences between the 2 groups
      may have been a result of increased adherence and the attainment of higher
      training loads during supervised training. The lack of differences in strength
      after the competition period indicates that supervision should be maintained to
      reduce substantial decrements in performance.

PMID- 22652918
TI  - Biomechanical analysis of standing long jump from varying starting positions.
AB  - The purpose of this study was (a) to investigate the effect of the different foot
      movement (placement) during take-off and the initial knee joint angle used in
      standing long jump by the ground reaction forces analysis and 3-dimensional
      motion analysis (BTS SMART motion) and (b) investigate how the jump performances
      of different foot placement is related to the electromyography (EMG) activity
      (Noraxon) of 3 selected muscle groups (m. gastrocnemius, m. gluteus maximus, m.
      rectus femoris, m. tibialis anterior, m. biceps femoris, and m. vastus medialis).
      Six high caliber sprinters (100 m: 10.87 +/- 0.38 seconds and 400 m: 46.75 +/-
      1.05 seconds) performed a series of jumps from parallel and straddle foot
      placement at take-off on a 2 force platform (Kistler model 9286B) to determine if
      a different pattern of take-off improves jumping distance. Using kinematic and
      kinetic data, the knee joint angle, the trajectories of center of mass (COM),
      magnitude of take-off peak force, and impulse during take-off phase were
      calculated. Average standing long jump performances with straddle foot placement
      were 13.58 cm (5.18%) above that from parallel feet placement. The take-off
      velocity with 90 degrees  knee initial angle initiation of take-off was not
      different (1.18 and 1.17 m.s, respectively) between the 2 jumps. The take-off
      angles on the COM trajectory also showed differences (69.87 and 66.8 degrees ,
      respectively) between each other. The contribution (EMG activation) made by the 6
      muscles were almost the same during all phases for the 2 jumps; however, some
      differences can be found, in either unilateral (single leg) or sums of both legs
      (bilateral) measurements. A recommendation can be formulated that the
      contribution of straddle foot placement during take-off can significantly
      increase the value of power measurement especially when the evaluation requires a
      complex movement structure with the division on the left and right legs, for
      example, sprint start from block.

PMID- 22652908
TI  - MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth
      muscle cell proliferation.
AB  - RATIONALE: Dedifferentiation of vascular smooth muscle cells (VSMC) leading to a
      proliferative cell phenotype significantly contributes to the development of
      atherosclerosis. Mitogen-activated protein kinase (MAPK) phosphorylation of
      proteins including connexin 43 (Cx43) has been associated with VSMC proliferation
      in atherosclerosis. OBJECTIVE: To investigate whether MAPK phosphorylation of
      Cx43 is directly involved in VSMC proliferation. METHODS AND RESULTS: We show in
      vivo that MAPK-phosphorylated Cx43 forms complexes with the cell cycle control
      proteins cyclin E and cyclin-dependent kinase 2 (CDK2) in carotids of
      apolipoprotein-E receptor null (ApoE(-/-)) mice and in C57Bl/6 mice treated with
      platelet-derived growth factor-BB (PDGF). We tested the involvement of Cx43 MAPK
      phosphorylation in vitro using constructs for full-length Cx43 (Cx43) or the Cx43
      C-terminus (Cx43(CT)) and produced null phosphorylation Ser>Ala
      (Cx43(MK4A)/Cx43(CTMK4A)) and phospho-mimetic Ser>Asp (Cx43(MK4D)/Cx43(CTMK4D))
      mutations. Coimmunoprecipitation studies in primary VSMC isolated from Cx43 wild
      type (Cx43(+/+)) and Cx43 null (Cx43(-/-)) mice and analytic size exclusion
      studies of purified proteins identify that interactions between cyclin E and Cx43
      requires Cx43 MAPK phosphorylation. We further demonstrate that Cx43 MAPK
      phosphorylation is required for PDGF-mediated VSMC proliferation. Finally, using
      a novel knock-in mouse containing Cx43-MK4A mutation, we show in vivo that
      interactions between Cx43 and cyclin E are lost and VSMC proliferation does not
      occur after treatment of carotids with PDGF and that neointima formation is
      significantly reduced in carotids after injury. CONCLUSIONS: We identify MAPK
      phosphorylated Cx43 as a novel interacting partner of cyclin E in VSMC and show
      that this interaction is critical for VSMC proliferation. This novel interaction
      may be important in the development of atherosclerotic lesions.

PMID- 22652919
TI  - Reliability and sensitivity of a repeated high-intensity exercise performance
      test for rugby league and rugby union.
AB  - The purpose of this study was to examine the reliability and sensitivity of 3
      ecologically valid repeated high-intensity exercise (RHIE) tests for professional
      rugby league (RL) and rugby union (RU) players. A further purpose was to
      investigate the relationship between RHIE performance and measures of speed (20-m
      sprint) and high-intensity intermittent running ability (yo-yo intermittent
      recovery test). Thirty-six RU and RL players were separated into 3 equal groups
      based on playing position: backs, RL forwards and RU forwards. Test-retest
      reliability was assessed by comparing total sprint time over 9 sprints during 2
      identical testing sessions. The intraclass correlation coefficients (ICCs) for
      total sprint time were moderate to high (0.82, 0.97, and 0.94) and coefficient of
      variation (CV) low (4.2, 1.4, and 0.6%) for the backs, RL forwards, and RU
      forwards tests, respectively. However, sprint performance decrement scores were
      poorer, with ICC and CV of 0.78, 0.86, and 0.88 and 49.5, 48.2, and 35.8% for the
      backs, RL forwards, and RU forwards, respectively. Total sprint times for the
      backs, RL forwards, and RU forwards decreased over the 3 tests by 0.54, 0.53, and
      2.09 seconds, respectively. Changes in RHIE total sprint time were moderately
      related to changes in 20-m sprint times (T1 to T2, r = 0.63; T2 to T3, r = 0.69;
      and T1 to T3, r = 0.63; all p < 0.05) but not yo-yo intermittent recovery test
      performances. This study has shown that the designed RL and RU RHIE tests have
      moderate to high reliability and produce significant improvements over a training
      period when total sprint times are compared.

PMID- 22652920
TI  - Are there any differences in physical fitness and throwing velocity between
      national and international elite female handball players?
AB  - This study compared physical characteristics in a 2003 national elite female team
      (NE; n = 16; fourth in the Spanish Championship) to the same team when it reached
      international level in 2009 (IE; n = 14; winner of the Spanish Championship and
      the European Handball Cup). Body height, body mass, body fat, and fat-free mass,
      1-repetition maximum bench press (1RMBP), vertical jumping height, handball
      throwing velocity, power-load relationship of the leg and arm extensor muscles, 5
      and 15-m sprint running time, and running endurance were measured in the second
      competitive mesocycle of a season. Results revealed that, compared with NE, IE
      players presented similar values in body mass, body height, sprint running time,
      handball throwing velocity, and jumping, but higher values (p < 0.01-0.05) in age
      (17%), 1RMBP (15%), power-load relationship of the arm (16%), and leg (10%)
      extensors, and endurance running velocities (7%). Significant correlations (r =
      0.71-0.72, p < 0.05) were observed in IE, but not in NE, between individual
      values of standing throw and individual values of power at 30% of 1RMBP, and
      individual values of power at 60% of body mass during half-squat actions. The
      present results suggest that more experienced, powerful and aerobically
      conditioned players are at an advantage in international-level female handball.
      The ball throwing velocity of international elite female handball players depends
      on their ability to produce muscle power at submaximal loads with the upper and
      lower extremities. However, in lower-level players, this depends on the level of
      performance at maximal strength of the upper extremities.

PMID- 22652921
TI  - Evaluation of the most intense high-intensity running period in English FA
      premier league soccer matches.
AB  - The aim of this study was to examine the most intense period of high-intensity
      running during elite soccer matches. Elite players (n = 100) were analyzed using
      a multicamera computerized tracking system. High-intensity running (speed >19.8
      km.h) in 5-min periods were quantified during matches. High-intensity running was
      performed for approximately 3% of total time, but this doubled (F[1,99] = 9.179,
      p < 0.001, d > 1.2) during the most intense period (8.4 +/- 2.7 vs. 16.4 +/- 4.6
      seconds). Recovery time between high-intensity efforts was approximately 30
      seconds during the most intense period (33.3 +/- 19.7 seconds). The work:rest
      ratio between high-intensity bouts increased (F[1,99] = 2.018, p < 0.001, d >
      0.6) from 1:12 for the match average to 1:2 during the most intense period. The
      distance of each discrete high-intensity running bout increased (F[1,99] = 1.958,
      p < 0.001, d > 0.6) approximately 13% during the most intense period compared
      with that of the match average (6.7 +/- 1.8 vs. 5.8 +/- 0.6 m). Central defenders
      were running at high-intensity for less (F[4,95] = 4.907, p < 0.05, d > 0.6) time
      than full-backs, wide midfielders, and attackers (12.9 +/- 2.4 vs. 17.9 +/- 3.4,
      18.3 +/- 5.5, and 16.9 +/- 3.8 seconds). Central defenders had a greater recovery
      time (F[4,95] = 3.083, p < 0.05, d > 0.6) between high-intensity efforts than
      wide midfielders. No differences were evident between playing positions for
      maximum running speed and average distances of high-intensity running. These
      results show that high-intensity running, work:rest ratios, and average high
      intensity distances change markedly during the most intense period of matches and
      are highly dependent on positional role. Therefore, conditioning drills and
      performance tests should closely mimic distances, work:rest ratios, and recovery
      times of those found during the most intense period of matches.

PMID- 22652923
TI  - Relative importance of genetic, ontogenetic, induction, and seasonal variation in
      producing a multivariate defense phenotype in a foundation tree species.
AB  - Plant adaptations for defense against herbivory vary both among species and among
      genotypes. Moreover, numerous forms of within-plant variation in defense,
      including ontogeny, induction, and seasonal gradients, allow plants to avoid
      expending resources on defense when herbivores are absent. We used an 18-year-old
      cottonwood common garden composed of Populus fremontii, Populus angustifolia, and
      their naturally occurring F(1) hybrids (collectively referred to as "cross
      types") to quantify and compare the relative influences of three hierarchical
      levels of variation (between cross types, among genotypes, and within individual
      genotypes) on univariate and multivariate phytochemical defense traits. Within
      genotypes, we evaluated ontogeny, induction (following cottonwood leaf beetle
      herbivory), and seasonal variation. We compared the effect sizes of each of these
      sources of variation on the plant defense phenotype. Three major patterns
      emerged. First, we observed significant differences in concentrations of defense
      phytochemicals among cross types, and/or among genotypes within cross types.
      Second, we found significant genetic variation for within-plant differences in
      phytochemical defenses: (a) based on ontogeny, levels of constitutive phenolic
      glycosides were nearly three times greater in the mature zone than in the
      juvenile zone within one cottonwood cross type, but did not significantly differ
      within another cross type; (b) induced levels of condensed tannins increased up
      to 65 % following herbivore damage within one cottonwood cross type, but were not
      significantly altered in another cross type; and (c) concentrations of condensed
      tannins tended to increase across the season, but did not do so across all cross
      types. Third, our estimates of effect size demonstrate that the magnitude of
      within-plant variation in a phytochemical defense can rival the magnitude of
      differences in defense among genotypes and/or cross types. We conclude that, in
      cottonwood and likely other plant species, multiple forms of within-individual
      variation have the potential to substantially influence ecological and
      evolutionary processes.

PMID- 22652924
TI  - Editorial: Pediatric bipolar disorder.

PMID- 22652926
TI  - Evidence-based assessment strategies for pediatric bipolar disorder.
AB  - Evidence-based assessment of pediatric bipolar disorder has advanced rapidly in
      the last two decades, moving from isolated clinical case descriptions to what is
      now a portfolio of techniques that include checklists from multiple informants,
      semi-structured diagnostic interviews and severity ratings, and technologies that
      allow daily tracking of mood and energy over the course of treatment. This review
      critically appraises (a) the need for evidence-based assessment of bipolar
      disorder as a common component of clinical practice, (b) triggers that warrant
      assessment of bipolar, (c) when best to deploy different techniques over the
      course of diagnosis and treatment, and (d) promising new developments in
      assessment. A decision-making framework is adapted from evidence-based medicine
      to guide assessment sequences in a patient-centered approach. Emphasis is placed
      on approaches that currently have the best validity and are feasible in most
      clinical practice settings. These methods increase accuracy and address many
      controversies surrounding pediatric bipolar diagnoses.

PMID- 22652927
TI  - Biological evidence for a neurodevelopmental model of pediatric bipolar disorder.
AB  - Bipolar disorder (BD) is a chronic illness with high morbidity and mortality.
      Pediatric onset BD has a more severe course of illness with higher rates of
      relapse and psychosocial impairment. Discovering interventions early in the
      course of BD in youth is paramount to preventing full illness expression and
      improve functioning in these individuals throughout the lifespan. It is therefore
      important to understand the mechanisms involved in the development of BD in order
      to determine which youth are at most risk and provide biological targets for
      early intervention. To serve this cause, we propose a neurodevelopmental model of
      BD, based on the existing data that implicate prefrontal-subcortical network
      dysfunction, caused by pre-existing genetic susceptibility and triggered by
      pathological reactions to stress and chronic inflammatory processes.

PMID- 22652925
TI  - Prevalence, clinical presentation and differential diagnosis of pediatric bipolar
      disorder.
AB  - BACKGROUND: Over the past 20 years, the evidence regarding pediatric bipolar
      disorder (BP) has increased substantially. As a result, recent concerns have
      focused primarily on prevalence and differential diagnosis. METHOD: Selective
      review of the literature. RESULTS: BP as defined by rigorously applying
      diagnostic criteria has been observed among children and especially adolescents
      in numerous countries. In contrast to increasing diagnoses in clinical settings,
      prevalence in epidemiologic studies has not recently changed. BPspectrum
      conditions among youth are highly impairing and confer high risk for conversion
      to BP-I and BP-II. Compared to adults, youth with BP have more mixed symptoms,
      more changes in mood polarity, are more often symptomatic and seem to have worse
      prognosis. The course, clinical characteristics, and comorbidities of BP among
      children and adolescents are in many ways otherwise similar to those of adults
      with BP. Nonetheless, many youth with BP receive no treatment and most do not
      receive BP-specific treatment. CONCLUSION: Despite increased evidence supporting
      the validity of pediatric BP, discrepancies between clinical and epidemiologic
      findings suggest that diagnostic misapplication may be common. Simultaneously,
      low rates of treatment of youth with BP suggest that withholding of BP diagnoses
      may also be common. Clinicians should apply diagnostic criteria rigorously in
      order to optimize diagnostic accuracy and ensure appropriate treatment.

PMID- 22652928
TI  - Diagnostic implications of informant disagreement about rage outbursts: bipolar
      disorder or another condition?
AB  - BACKGROUND: Modest agreement between parent- and teacher-reports of child
      behavior is a common finding. This study examines diagnoses made when significant
      disparity occurs in parent- and teacher-reports of rage behaviors. METHODS:
      Parents and teachers of 911 5-18 year-olds referred for psychiatric outpatient
      services completed rating scales and received a psychiatric evaluation blind to
      parent- and teacher-ratings. Children with rage outbursts (n=431, 47.2%) were
      assessed for diagnosis, family history, and clinical variables. RESULTS: Children
      were 12.0 (3.6) years; 26.5% were female. Bipolar disorder was rare (11.2%) in
      this sample; however, in children with parent- and teacher-reported rages, severe
      mood dysregulation was the most common condition (54.4%). In parent only reported
      rages, anxiety disorders were most common (40.6%) diagnoses, and in teacher only
      reported rages, learning/language disorders were the most common (46.0%)
      diagnoses. CONCLUSION: The context in which a rage outburst occurs may impact the
      diagnosis; however, diagnosis alone does not explain this difficult and impairing
      behavior.

PMID- 22652929
TI  - Beyond dogma: from diagnostic controversies to data about pediatric bipolar
      disorder and children with chronic irritability and mood dysregulation.
AB  - From the mid-1990s through the present, studies have demonstrated a significant
      rise in the numbers of children and adolescents diagnosed with bipolar disorder
      (BD). Why is this? The present manuscript reviews several possibilities, most
      notably ambiguity in the diagnostic criteria for mania and how they may apply to
      children with functionally-impairing irritability. Furthermore, we discuss
      ongoing phenomenological and affective neuroscience research approaches to
      address those children most on the fringes of our current psychiatric nosology.
      In summary, these studies suggest that BD youths may be distinguished on some
      measures from those with chronic irritability and severe mood dysregulation,
      although the two groups also have some shared deficits.

PMID- 22652930
TI  - A magnetic resonance spectroscopy study of the anterior cingulate cortex in youth
      with emotional dysregulation.
AB  - BACKGROUND: The main aim of this study was to use proton Magnetic Resonance
      Spectroscopy (MRS) to identify brain biomarkers for emotional dysregulation in
      youth as measured by subscales of the Child Behavior Checklist (CBCL). METHODS:
      We measured glutamate (Glu) concentrations in the anterior cingulated cortex
      (ACC) of 37 pediatric subjects (aged 6-17 years) using high field (4.0 Tesla)
      proton Magnetic Resonance Spectroscopy (MRS). Subjects were grouped based on
      combined T scores on three subscales (Anxiety/Depression, Aggression and
      Attention) of the CBCL previously associated with deficits in the regulation of
      emotion. Subjects were stratified into those with high (> 180) (N=10) and low (<
      180) (N=27) scores. LIMITATIONS: Limitations include small sample size, wide age
      range studied, focus on Anterior Cingulate Cortex (ACC) only, and that some
      subjects received psychopharmacological treatments. RESULTS: We found a
      statistically significant correlation between Glu levels in the ACC and CBCL
      dysregulation profile scores among subjects with high dysregulation profile
      scores. CONCLUSIONS: These results suggest that glutamatergic dysregulation in
      the ACC may represent a useful biomarker of emotional dysregulation in youth.
      Further investigation into the causality, time line and utility as a predictive
      metric is warranted.

PMID- 22652931
TI  - High-sensitivity in vivo imaging for tumors using a spectral up-conversion
      nanoparticle NaYF4: Yb3+, Er3+ in cooperation with a microtubulin inhibitor.
AB  - Fluorescein has been used for in vivo imaging to identify tumors. However, this
      technique presents several limitations, mainly due to its limited targeting
      efficiency, tissue autofluorescence and poor light penetration in tissue. In the
      present study, an alternative fluorescence imaging technique to localize tumors
      has been developed by using up-conversion nanoparticles (UCNs) and enhanced
      targeting approaches. A folic acid molecule is conjoined with UCNs (NaYF(4):
      Yb(3+), Er(3+)) to improve the tumor-specificity; the UCN is also loaded with the
      microtubule inhibitor CA4P, to further improve the local delivery of particles in
      the tumor. The proposed imaging technique combines several well-established
      individual concepts into one novel integrated procedure and significantly
      improves its tumor-imaging capability: the near-infrared excitation for UCNs
      minimizes tissue autofluorescence and allows imaging into deeper tissue; the
      improvement in the signal to noise ratio (SNR) is at least a magnitude better
      than that of a conventional fluorescence imaging technique, and the modification
      of UCNs with folic acid significantly improves the tumor targeting efficiency by
      utilizing its affinity for the folic acid receptor that is often over expressed
      in tumors. The loading of CA4P further helps UCNs to cross blood vessel walls to
      reach tumor cells by depolymerizing the microtubules of endothelial cells. The
      integrated nanoparticle possesses the near-infrared-identical optical properties
      of UCNs alone, thus achieving a highly effective fluorescence imaging probe. The
      results demonstrated that the proposed method provides an excellent alternative
      for tumor localization and a potential traceable vehicle for highly efficient
      drug delivery.

PMID- 22652932
TI  - Slowing down and stretching DNA with an electrically tunable nanopore in a p-n
      semiconductor membrane.
AB  - We have studied single-stranded DNA translocation through a semiconductor
      membrane consisting of doped p and n layers of Si forming a p-n-junction. Using
      Brownian dynamics simulations of the biomolecule in the self-consistent membrane
      electrolyte potential obtained from the Poisson-Nernst-Planck model, we show that
      while polymer length is extended more than when its motion is constricted only by
      the physical confinement of the nanopore. The biomolecule elongation is
      particularly dramatic on the n-side of the membrane where the lateral membrane
      electric field restricts (focuses) the biomolecule motion more than on the p
      side. The latter effect makes our membrane a solid-state analog of the alpha
      hemolysin biochannel. The results indicate that the tunable local electric field
      inside the membrane can effectively control dynamics of a DNA in the channel to
      either momentarily trap, slow down or allow the biomolecule to translocate at
      will.

PMID- 22652934
TI  - Pressure ulcer prevalence in Turkey: a sample from a university hospital.
AB  - PURPOSE: The purpose of this study was to identify pressure ulcer prevalence
      among hospitalized patients in a university hospital setting. SETTING AND
      SUBJECTS: The study setting was medical and surgical inpatient wards and critical
      care units in a university hospital in Adana, Turkey. The sample population
      comprised 404 patients who were aged 18 years or older and admitted to the
      intensive care units and internal and surgery units at least 24 hours before data
      collection. METHODS: Each participating patient's skin was assessed and pressure
      ulcers were classified according to the National Pressure Ulcers Advisory Panel
      grading system. Pressure ulcer risk was assessed using the Braden Scale. Data
      were recorded on a patient observation form designed for this study. INSTRUMENTS:
      The following tools were used to collect data: (a) data collection form in
      identifying sociodemographic and medical characteristics of the patients, (b) the
      classification developed by the National Pressure Ulcers Advisory Panel in
      identifying the phases and localization of pressure ulcers, and (c) Braden Risk
      Assessment Scale in assessing risks. RESULTS: The average age of patients was
      51.22 +/- 0.84 years (mean +/- SD); 51.7% were male. The mean hospital length of
      stay was 9.6 +/- 0.5 days. Pressure ulcer risk assessment revealed that 34.2% of
      the patients were at increased risk. The prevalence of pressure ulcers was 10.4%.
      Pressure ulcers occurred most frequently in the sacral area (43.9%); 45.2% of
      them were stage (grade) II. CONCLUSIONS: The pressure ulcer prevalence identified
      in this study is comparable with studies conducted in other countries.

PMID- 22652933
TI  - Factors associated with sustained attention during an activity intervention in
      persons with dementia.
AB  - BACKGROUND/AIMS: Are the noncognitive factors of self-reported mood and
      personality related to sustained attention in nursing home residents with
      dementia during an activity intervention? METHODS: Intervention data from a
      randomized clinical trial were used to address the aim of this project. Subjects
      were 128 nursing home residents who were assessed for mood, personality,
      behavioral indicators of attention, time on task and number of disengagements
      during an activity intervention. RESULTS: More positive self-reported mood was
      associated with greater behavioral displays of attention during activities,
      greater time spent engaged in the activities and less disengagement. CONCLUSION:
      To our knowledge, this is the first study to report on the association of mood,
      personality and sustained attention in nursing home residents with dementia.
      While the findings are preliminary, they can be used to inform the design of
      future research.

PMID- 22652935
TI  - More than skin deep: developing a hospital-wide Wound Ostomy Continence Unit
      Champion program.

PMID- 22652936
TI  - Urinary incontinence among Turkish women: an outpatient study of prevalence, risk
      factors, and quality of life.
AB  - PURPOSE: The aim of this study was to determine the prevalence and potential risk
      factors associated with urinary incontinence (UI) in women and to assess its
      impact on quality of life (QOL). DESIGN: We undertook a cross-sectional study
      based on interviews, using a structured questionnaire. SUBJECTS AND SETTING: Two
      hundred eighty-eight women, aged 19 years and older, from gynecology outpatient
      clinics attached to a university hospital in Ankara, Turkey, were interviewed.
      INSTRUMENTS: Data were collected via a Turkish version of the international
      consultation on incontinence questionnaire short form (ICIQ-SF) and the Wagner's
      quality of life scale. METHODS: Data were collected by face-to-face interviews
      with subjects and took approximately 30 minutes to complete. Potential risk
      factors were analyzed using logistic regression. RESULTS: The prevalence of UI
      was 31.9%. Logistic regression analysis indicated that the number of pregnancies
      (odds ratio [OR] = 0.53, 95% CI: 0.28-0.99), UI in mother (OR = 2.46, 95% CI:
      1.35-4.50) and sister (OR = 0.34, 95% CI: 0.16-0.77), previous UI during
      pregnancy (OR = 12.22, 95% CI: 4.11-36.36) and postpartum period (OR = 11.28, 95%
      CI: 3.66-34.76), and body mass index (OR = 0.49, 95% CI: 0.29-0.85) were
      associated with a higher likelihood of incontinence (P < .05). Ninety-two of 288
      women (31.9%) stated that UI has a negative impact on their QOL and only 40 of 92
      (43.5%) had asked for medical help. Impairment of QOL was related with the type
      of UI, frequency of UI episode, and amount of leakage. CONCLUSION: Our study
      results determined that UI is common in Turkish women. The QOL of women was
      mostly mildly or moderately affected by UI.

PMID- 22652937
TI  - Factors impacting the quality of life of people with an ostomy in North America:
      results from the Dialogue Study.
AB  - PURPOSE: The purpose of this study was to evaluate skin condition and quality of
      life following the use of a double-layer adhesive pouching system. This article
      reports results from North American participants. DESIGN: The study was an open
      label, noncomparative, multicenter study. SUBJECTS AND SETTING: Seven hundred
      forty-three persons with ostomies who reside in North America participated in the
      study. INSTRUMENTS: A stoma-quality of life (QOL) questionnaire consisting of 20
      questions was used to measure health-related quality of life. The Ostomy Skin
      Tool was used to assess peristomal skin condition. METHODS: Peristomal skin and
      health-related quality of life were assessed by WOC nurses at baseline and again
      after 6 to 8 weeks following the use of a double-layer adhesive ostomy pouching
      system. The participants recorded self-reported leakage level, presence of
      peristomal skin disorder, use of appliance type (e.g., convex, 1- or 2-piece),
      and frequency of consultation with the WOC nurse. RESULTS: Participants
      experienced a significant decrease in frequency of pouch leakage (P < .0001) and
      accessory use, improvement of skin condition, and overall significant improvement
      in mean quality of life score (56.8 vs. 58.9, P < .0001). The greatest change on
      the Stoma-QOL scores was observed in the quartile of participants with the lowest
      QOL at baseline. Their QOL scores rose from a mean 43.8 at visit 1 to 50.1 at
      visit 2 (P < .0001). CONCLUSION: The combination of a regular contact with a WOC
      nurse and the use of a double-layer adhesive appliance led to a significant
      reduction in leakage and accessory use, improved skin condition, and significant
      improvement in health-related quality of life.

PMID- 22652938
TI  - Developing the standardized wound care documentation model: a Delphi study to
      improve the quality of patient care documentation.
AB  - OBJECTIVE: The aim of this study was to validate a set of previously developed
      criteria for wound care documentation and to use the validated criteria as a
      framework for developing a wound care documentation model. The Skin Integrity
      component of the Finnish Care Classification, the Finnish Classification of
      Nursing Diagnosis, and the Finnish Classification of Nursing Interventions serve
      as the basis for the wound care documentation model. SUBJECTS AND SETTING:
      Finnish wound care specialists, mainly nurses, from different Finnish hospitals,
      and from the Finnish Wound Care Society having on average 18 years of experience
      in wound management. Data were collected using electronic survey technology.
      METHODS: A Delphi technique was used to develop and validate the documentation
      system. RESULTS: The final model consists of 7 main categories and 25
      subcategories of the Skin Integrity component of the Finnish Classification of
      Nursing Diagnosis and 5 main categories and 25 subcategories of the Skin
      Integrity component of the Finnish Classification of Nursing Intervention. Based
      on the results of the Delphi survey, consensus was reached on all elements of the
      wound care documentation model. CONCLUSION: The Delphi process was used to
      develop a wound care documentation model for use in an electronic record to
      promote systematic documentation of both wound assessment and wound care. Future
      research should address the utility of this documentation model for nurses with
      expertise in wound care and generalist nurses.

PMID- 22652939
TI  - Effectiveness of apoptotic factors expressed on the wounds of patients with stage
      III pressure ulcers.
AB  - PURPOSE: The purpose of this study was to explore the expression of apoptotic
      factors in stage III pressure ulcers and explain their effects on wound healing.
      SUBJECTS AND SETTING: The sample comprised 8 patients with stage III pressure
      ulcers, along with 4 volunteers with normal skin who were undergoing elective
      surgical procedures. METHODS: Eight patient tissue specimens from wound of stage
      III pressure ulcers were obtained from hospitalized patients. Tissue specimens
      from 4 volunteer patients were obtained during surgery. All 12 tissue specimens
      were analyzed for presence of apoptosis-related factors including bax/bcl-2 (B
      cell lymphoma 2), Fas/fasL (Fas ligand), and terminal deoxynucleotide transferase
      mediated dUTP nick end labeling (TUNEL) as well as immunohistochemical analysis
      with Fas/FasL. RESULTS: Bax positive cells were strongly expressed from
      surrounding zone to center zone in the specimens obtained from stage III pressure
      ulcers, and Bcl-2 expression staining decreased contrarily (P < .01). Comparison,
      apoptotic factors bax positive cell and fas/fasL mRNA expression occurred rarely
      in tissue specimens from the control group. Fas/fasL mRNA-positive granules were
      detected in epidermal cells and fibroblasts, demonstrating a progressive increase
      from the margin of the pressure ulcers progressing toward the center of the wound
      bed. We also found an increased intensity of TUNEL staining in ulcer center as
      well as wound margin, compared with control skin tissue. CONCLUSION: These
      results suggest that molecular regulators of apoptosis are involved in pressure
      ulcer wound healing. Results also suggest that differences in the expression and
      distribution of the apoptotic related factors in stage III pressure ulcers play
      an important role in the delayed wound healing characteristic of these complex
      wounds.

PMID- 22652942
TI  - The effect of prednisolone on sequelae in Bell's palsy.
AB  - OBJECTIVE: To study whether prednisolone reduces sequelae in Bell's palsy.
      DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter
      trial with 12 months of follow-up. SETTING: Seventeen referral centers. PATIENTS:
      In all, 829 patients aged 18 to 75 years. INTERVENTIONS: Randomization within 72
      hours in a factorial fashion to placebo plus placebo (n = 206); prednisolone, 60
      mg/d for 5 days, with the dosage then tapered for 5 days, plus placebo (n = 210);
      valacyclovir hydrochloride, 1000 mg 3 times daily for 7 days, plus placebo (n =
      207); or prednisolone plus valacyclovir (n = 206). MAIN OUTCOME MEASURES: Facial
      function at 12 months assessed with the Sunnybrook and House-Brackmann grading
      systems. RESULTS: In 184 of the 829 patients, the Sunnybrook score was less than
      90 at 12 months; 71 had been treated with prednisolone and 113 had not (P <
      .001). In 98 patients, the Sunnybrook score was less than 70; 33 had received
      prednisolone and 65 had not (P < .001). The difference between patients who
      received prednisolone and who did not in House-Brackmann gradings higher than I
      and higher than II was also significant (P < .001 and P = .01, respectively). No
      significant difference was found between patients who received prednisolone and
      those who did not in Sunnybrook scores less than 50 (P = .10) or House-Brackmann
      grades higher than III (P = .80). Synkinesis was assessed with the Sunnybrook
      score in 743 patients. Ninety-six patients had a synkinesis score more than 2, of
      whom 33 had received prednisolone and 63 had not (P = .001). Sixty patients had a
      synkinesis score more than 4, of whom 22 had received prednisolone and 38 had not
      (P = .005). CONCLUSION: Prednisolone significantly reduces mild and moderate
      sequelae in Bell's palsy. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00510263.

PMID- 22652943
TI  - Septal batten graft to correct cartilaginous deformities in endonasal
      septoplasty.
AB  - OBJECTIVE: To evaluate the usefulness of septal batten grafts to correct
      cartilaginous septal deformities in endonasal septoplasty. DESIGN: Retrospective
      study. SETTING: University medical center. PATIENTS: Of 430 patients who
      underwent endonasal septoplasties from January 2006 to January 2011, 30 received
      septal batten grafts and were enrolled in the study. Twenty-eight patients were
      male and 2 were female. MAIN OUTCOME MEASURES: Thirty consecutive patients
      received septal batten grafts and were followed up for more than 6 months.
      Patterns of septal deformity, materials used for batten graft, surgical results,
      symptom improvement, findings of acoustic rhinometry, and surgical complications
      were investigated. RESULTS: Among the 30 patients, 5 were revision cases. Most of
      the deformities were characterized as moderate to severe degrees of curved or
      angulated deviations of the cartilaginous septum. The batten graft was performed
      with either septal cartilage (n = 21) or bony septum (n = 9). A straight septum
      was achieved in 90% of all procedures. Subjective symptoms of nasal obstruction
      were improved in all patients, as evaluated by the Nasal Obstruction Symptom
      Evaluation scale. Acoustic rhinometry revealed that after surgery the mean
      minimal cross-sectional area changed from 0.33 cm2 to 0.42 cm2 (P = .02) and the
      nasal volume from 4.71 mL to 6.28 mL (P = .02). There were no major
      complications, eg, septal perforation or saddle nose, and no revision surgery was
      needed. CONCLUSION: Endonasal septal batten graft is a safe, useful, and
      effective technique to straighten moderate to severe septal cartilage deformities
      that are otherwise not correctable via conventional septoplasty techniques.

PMID- 22652944
TI  - Bacterial biofilm associated with chronic laryngitis.
AB  - OBJECTIVE: To determine the incidence of biofilm on the vocal fold epithelium of
      patients with chronic laryngitis. Bacteria can grow in biofilm protected by a
      glycoprotein mass. Recent studies have shown the importance of biofilm in chronic
      otolaryngologic infections. Because chronic laryngitis is often recurrent and
      occasionally purulent, we hypothesized that it is biofilm related. DESIGN:
      Prospective, controlled, blinded study. Epithelial biopsy specimens from true
      vocal folds from patients with chronic laryngitis undergoing diagnostic
      laryngomicroscopy were prepared for confocal scanning laser microscopy (CSLM) and
      polymerase chain reaction (PCR) microarray: CSLM images were evaluated for
      bacterial biofilm morphologic characteristics; PCR with microarray-based
      diagnostic assay was used to identify the bacterial species involved. Patients
      with vocal fold polyp served as control cases. SETTING: Tertiary care university
      hospital. PATIENTS: Eighteen consecutive patients were enrolled in the study.
      Thirteen of them had chronic laryngitis, and 5 had vocal fold polyps. RESULTS: In
      9 cases, the CSLM revealed bacterial growth in biofilm form, and most of these
      specimens (8 out of 9) were from patients with chronic laryngitis. The PCR
      results were positive in 13 cases, including all 9 biofilm-positive cases.
      CONCLUSIONS: Direct detection of biofilm in laryngeal biopsy specimens from
      patients with chronic laryngitis supports the hypothesis that chronic laryngitis
      may be biofilm related. Biofilm was found in 62% of the cases of chronic
      laryngitis. To our knowledge, this is the first report of bacterial biofilm
      associated with chronic laryngitis; however, further investigation is warranted
      before a clear conclusion can be drawn.

PMID- 22652945
TI  - Treatment strategies for lateral sphenoid sinus recess cerebrospinal fluid leaks.
AB  - OBJECTIVE: To highlight concepts critical to achieving successful repair and
      avoiding intracranial complications in the treatment of cerebrospinal fluid (CSF)
      leaks from the lateral recess of the sphenoid sinus (LRS). DESIGN: Outcomes
      study. SETTING: Tertiary referral university hospital. PATIENTS: Eleven patients
      with LRS CSF leaks from June 2008 to June 2010. INTERVENTIONS: Endoscopic
      transpterygoid approach and multilayer repair of skull base defect in the LRS.
      MAIN OUTCOME MEASURES: Recurrence, graft techniques, postoperative intracranial
      pressure (ICP), and use of ventriculoperitoneal (VP) shunt. RESULTS: Thirteen CSF
      leaks originating in the LRS were surgically repaired in 11 patients; 2 patients
      required bilateral leak repair. The endoscopic transpterygoid approach was used
      in 12 of 13 repairs. Eight patients had failed attempts at repair prior to
      presentation (4 endoscopic sphenoidotomies and 4 middle cranial fossa [MCF]
      approaches). One patient presented with a temporal lobe abscess following
      hydroxyapatite "obliteration" to seal off the LRS. This required a combined
      MCF/transpterygoid approach to drain the abscess, remove the encephalocele and
      hydroxyapatite, and seal the skull base defect. In 2 cases, the LRS was left
      patent owing to concerns of inadequate mucosal extirpation. The median duration
      of follow-up was 10.8 months (range, 2-29 months). One patient experienced a
      failure (2 months after repair), which was successfully sealed on the second
      attempt. Postoperatively, 5 patients required VP shunts, and 5 were maintained on
      acetazolamide for elevated ICP (average, 26.7 cm H2O in 8 patients; presumed
      elevated in 2 patients). CONCLUSIONS: The current study demonstrated a 92%
      success rate using the endoscopic transpterygoid approach for LRS skull base
      defects providing support for routine use in the treatment algorithm. Poor
      outcomes were observed with previous surgical attempts to obstruct the LRS
      without repairing the skull base defect.

PMID- 22652946
TI  - The effect of positional dependency on outcomes of treatment with a mandibular
      advancement device.
AB  - OBJECTIVE: To evaluate retrospectively the efficacy of the mandibular advancement
      device (MAD) in patients with obstructive sleep apnea in terms of positional
      dependency. DESIGN: Retrospective analysis. SETTING: Academic tertiary referral
      center. PATIENTS: One hundred patients with obstructive sleep apnea treated with
      the MAD at the Department of Otorhinolaryngology sleep clinic were included from
      January 1, 2005, through December 31, 2010. INTERVENTIONS: All patients underwent
      nocturnal full-night polysomnography before and at least 3 months after intraoral
      MAD application. MAIN OUTCOME MEASURES: Treatment results and prognostic factors
      deciding the success of MAD application. RESULTS: Of the 100 patients, 80 showed
      positional dependency and 20 showed nondependency. In the position-dependent
      obstructive sleep apnea group, the median (interquartile range) apnea-hypopnea
      index (AHI) decreased from 32.1 (24.4-41.9) to 8.6 (3.7-13.8) (P < .001); in the
      nondependent group, from 56.4 (26.2-71.5) to 15.7 (6.8-30.7) (P < .001). The
      success rate (AHI reduction >=50% and AHI <10) was 57.5% and 30.0% in position
      dependent and position-nondependent groups, respectively (P = .04). CONCLUSION:
      Identifying patients with obstructive sleep apnea as position dependent or
      nondependent may have important therapeutic implications in predicting the
      outcome of MAD treatment.

PMID- 22652947
TI  - Vertical partial laryngectomy with temporoparietal free flap reconstruction for
      recurrent laryngeal squamous cell carcinoma: technique and long-term outcomes.
AB  - OBJECTIVES: To present a technique for reconstruction of the vertical partial
      laryngectomy defect using a vascularized carrier consisting of a temporoparietal
      free flap, cartilage graft, and buccal mucosal graft; to evaluate the oncologic
      outcomes with respect to locoregional control and overall survival; and to
      provide an assessment of patient quality of life and functional outcomes. DESIGN:
      Retrospective medical record review and prospective cross-sectional analysis of
      functional outcomes. SETTING: Princess Margaret Hospital-University Health
      Network and the Odette Cancer Centre-Sunnybrook Health Sciences Centre. METHODS:
      We collected data on patient demographic characteristics, tumor staging, initial
      treatment, recurrence, management, and follow-up. Prospectively, a cross
      sectional study was performed using the European Organization for Research and
      Treatment of Cancer Quality of Life of Cancer Patients Questionnaire C30 and HN35
      module and voice and swallowing results using the Voice Handicap Index and
      Swallowing Quality of Life index. MAIN OUTCOME MEASURES: Local recurrence-free
      survival, cause-specific survival, and overall survival. RESULTS: Forty men met
      inclusion criteria (median age, 65.0 years). Local recurrence-free survival was
      84% at 3 years and 75% at 5 years. Cause-specific survival was 88% at 3 years and
      78% at 5 years. Thirty-eight patients were successfully decannulated; all
      patients tolerated oral intake after the surgical procedure. The C30 and HN35
      symptomatic results were comparable with patients with standardized stages I and
      II head and neck tumors. The Voice Handicap Index results were comparable with
      patients with functional dysphonia. Patients' swallowing was in the normal range.
      CONCLUSIONS: Patients receiving vertical partial laryngectomy with
      temporoparietal free flap reconstruction for recurrent glottic carcinoma
      following radiation treatment failure have high rates of locoregional control.
      The use of the temporoparietal free flap in this patient population produces high
      quality voice results and normal swallowing and has no major effect on quality of
      life.

PMID- 22652948
TI  - Long-term results of bilateral endoscopic vidian neurectomy in the management of
      moderate to severe persistent allergic rhinitis.
AB  - OBJECTIVE: To evaluate the long-term efficacy of bilateral endoscopic vidian
      neurectomy in the management of moderate to severe persistent allergic rhinitis.
      DESIGN: A prospective reassessment of the postoperative long-term results of
      bilateral endoscopic vidian neurectomy using the Rhinoconjunctivitis Quality of
      Life Questionnaire and visual analog scale for patients with moderate to severe
      persistent allergic rhinitis. SETTING: University hospital. PATIENTS: A total of
      236 patients with moderate to severe persistent allergic rhinitis were divided
      into the following 3 treatment groups: those who underwent bilateral endoscopic
      vidian neurectomy (group 1, n = 93), those who underwent partial inferior
      turbinectomy and/or septoplasty (group 2, n = 51), and those who received
      conservative therapy (controls, n = 92). MAIN OUTCOME MEASURE: The patients'
      quality of life was assessed at 6 months, 1 year, and 3 years after undergoing
      the initial selected treatments for moderate to severe persistent allergic
      rhinitis. The complications were observed after treatment. RESULTS: Data from 199
      of 236 patients who had complete follow-up documents were statistically analyzed.
      The average posttreatment bilateral endoscopic vidian neurectomy scores of the
      Rhinoconjunctivitis Quality of Life Questionnaire and visual analog scale were
      significantly improved at 6 months, 1 year, and 3 years compared with
      pretreatment scores for group 1 (P < .00) and for those in groups 2 and 3 during
      the same period. By the patient's self-evaluation posttreatment, the percentages
      of much improved, improved, and not improved was 64.7% (55 cases), 24.7% (21
      cases), and 10.6% (9 cases), respectively. The percentages were significantly
      higher for those in group 1 than for those in group 2 (P < .05). No severe
      complication occurred in all 3 patient groups. CONCLUSION: In the hands of a well
      trained surgeon bilateral endoscopic vidian neurectomy is an effective and safe
      technique in the management of moderate to severe persistent allergic rhinitis.

PMID- 22652950
TI  - Evaluation and management of the patient with postoperative facial paralysis.
AB  - Postoperative facial paralysis comprises a spectrum of injuries ranging from
      mild, temporary weakness to severe, permanent paralysis, affecting as little as
      one muscle group to as much as the full hemiface. Herein is presented an
      introductory review of iatrogenic facial paralysis, from initial evaluation and
      decision making to the full range of conservative and operative management.

PMID- 22652949
TI  - Frontoethmoidal and intraorbital osteomas: exploring the limits of the endoscopic
      approach.
AB  - OBJECTIVE: To review our experience with the surgical treatment of
      frontoethmoidal osteomas, focusing on the osteomas that were either localized
      laterally in the frontal sinus or showing intraorbital involvement. DESIGN:
      Retrospective evaluation. SETTING: Tertiary care center. PATIENTS: Patients with
      symptomatic frontoethmoidal or intraorbital osteomas who had been treated
      surgically from 1996 through 2011. INTERVENTION: Sixty frontoethmoidal osteomas
      were treated surgically. The lesion involved the far lateral portion of the
      frontal sinus in 23 cases and the orbital region in 6 cases. In 31 cases, a
      purely endoscopic approach was performed while a combined procedure was used in
      25 patients. In 4 patients, an exclusively external approach was required. MAIN
      OUTCOME MEASURE: No recurrence of osteoma. RESULTS: Radical resection was
      obtained, except in the case of 2 lesions. No osteoma recurrence was observed
      during a mean follow-up of 72.6 months. CONCLUSIONS: The size of the osteoma, far
      lateral extension of the tumor in the frontal sinus beyond the lamina papyracea,
      and intraorbital involvement are no longer absolute contraindications for purely
      transnasal endoscopic resection. What is important is that the surgeon should not
      be dogmatic but rather be ready to change his or her mind during surgery,
      shifting to an external approach when required.

PMID- 22652951
TI  - More than a frog in the throat: a case series and review of localized laryngeal
      amyloidosis.

PMID- 22652952
TI  - Prepontine epidural abscess: a rare complication of bacterial rhinosinusitis.

PMID- 22652955
TI  - Radiology quiz case 2. Pyriform sinus fistula.

PMID- 22652953
TI  - Radiology quiz case 1. Non-Hodgkin lymphoma (NHL) (diffuse large B-cell type) of
      the frontal sinus.

PMID- 22652957
TI  - Pathology quiz case 1. Small cell carcinoma (SmCC) of the larynx.

PMID- 22652959
TI  - Pathology quiz case 2. Multifocal nodular oncocytic hyperplasia (MNOH).

PMID- 22652961
TI  - Notice of retraction: duplicate data reported in "Anatomical variability of the
      maxillary artery: findings from 100 Asian cadaveric dissections" (Arch
      Otolaryngol Head Neck Surg. 2010;136[8]:813-818.).

PMID- 22652962
TI  - In situ IR study of surface hydroxyl species of dehydrated TiO2: towards
      understanding pivotal surface processes of TiO2 photocatalytic oxidation of
      toluene.
AB  - The surface species on P25-TiO(2) were characterized by FTIR after evacuation at
      50-550  degrees C. The functions of OH groups on P25-TiO(2) catalysts have been
      tested by the adsorption and photooxidation of toluene in an in situ IR cell.
      FTIR studies show that the hydroxyl species on P25-TiO(2) are clearly temperature
      dependent and P25-TiO(2) has six isolated hydroxyls with bands at 3734, 3715,
      3688, 3671, 3658 and 3640 cm(-1). The OH groups on P25 play different roles in
      the photo-oxidation process: surface hydroxyls with bands at 3688, 3671, 3658 and
      3640 cm(-1) act as adsorption sites while surface hydroxyls with bands at 3734
      and 3715 cm(-1) act as sources of the OH radical.

PMID- 22652963
TI  - Abstracts of EDHF 2012, the 10th Anniversary Meeting. Vaux-de-Cernay. France.
      June 27-30, 2012.

PMID- 22652964
TI  - Nucleoside-5'-phosphorothioate analogues are biocompatible antioxidants
      dissolving efficiently amyloid beta-metal ion aggregates.
AB  - Amyloid beta (Abeta) peptide is known to precipitate and form aggregates with
      zinc and copper ions in vitro and, in vivo in Alzheimer's disease (AD) patients.
      Metal-ion-chelation was suggested as therapy for the metal-ion-induced Abeta
      aggregation, metal-ion overload, and oxidative stress. In a quest for
      biocompatible metal-ion chelators potentially useful for AD therapy, we tested a
      series of nucleoside 5'-phosphorothioate derivatives as re-solubilization agents
      of Cu(+)/Cu(2+)/Zn(2+)-induced Abeta-aggregates, and inhibitors of Fenton
      reaction in Cu(+) or Fe(2+)/H(2)O(2) system. The most promising chelator in this
      series was found to be APCPP-gamma-S. This nucleotide was found to be more
      efficient than EDTA in re-solubilization of Abeta(40)-Cu(2+) aggregates as
      observed by the lower diameter, d(H), (86 vs. 64 nm, respectively) obtained in
      dynamic light scattering measurements. Likewise, APCPP-gamma-S dissolved
      Abeta(40)-Cu(+) and Abeta(42)-Cu(2+)/Zn(2+) aggregates, as monitored by (1)H-NMR
      and turbidity assays, respectively. Furthermore, addition of APCPP-gamma-S to
      nine-day old Abeta(40)-Cu(2+)/Zn(2+) aggregates, resulted in size reduction as
      observed by transition electron microscopy (diameter reduction from 2.5 to 0.1
      MUm for Abeta(40)-Cu(2+) aggregates). APCPP-gamma-S proved to be more efficient
      than ascorbic acid and GSH in reducing OH radical production in Fe(2+)/H(2)O(2)
      system (IC(50) values 85, 216 and, 92 MUM, respectively). Therefore, we propose
      APCPP-gamma-S as a potential AD therapy capable of both reducing OH radical
      production and re-solubilization of Abeta(40/42)-M(n+) aggregates.

PMID- 22652965
TI  - [Model to estimate epidemic patterns of influenza A (H1N1) in Mexico].
AB  - OBJECTIVE: Apply a mathematical model to estimate the epidemic patterns of
      influenza A (H1N1) in Mexico during the stages of application and suspension of
      measures to mitigate the epidemic. METHODS: The effective reproductive number (R)
      for each state of Mexico during and after the application of social distancing
      measures was estimated by the SIR model (susceptible, infected, and recovered
      individuals) based on data published by the Ministry of Health of Mexico.
      RESULTS: From the beginning of the outbreak until suspension of school activities
      (28 April-13 May 2009), the national median of R was 1.13. In the following
      period (14 May-17 July 2009) the national median of R decreased to 1.01.
      CONCLUSIONS: It was demonstrated that several epidemic scenarios occurred at the
      national level. It is suggested that heterogeneous patterns at the state level be
      taken into account in decision-making on the adoption of measures to mitigate
      influenza epidemics.

PMID- 22652966
TI  - Comparison of crude and adjusted mortality rates from leading causes of death in
      northeastern Brazil.
AB  - OBJECTIVE: To present how the adjustment of incompleteness and misclassification
      of causes of death in the vital registration (VR) system can contribute to more
      accurate estimates of the risk of mortality from leading causes of death in
      northeastern Brazil. METHODS: After estimating the total numbers of deaths by age
      and sex in Brazil's Northeast region in 2002-2004 by correcting for undercount in
      the VR data, adjustment algorithms were applied to the reported cause-of-death
      structure. Average annual age-standardized mortality rates were computed by
      cause, with and without the corrections, and compared to death rates for Brazil's
      South region after adjustments for potential misdiagnosis. RESULTS: Death rates
      from ischemic heart disease, lower respiratory infections, chronic obstructive
      pulmonary disease, and perinatal conditions were more than 100% higher for both
      sexes than what was suggested by the routine VR data. Corrected cause-specific
      mortality rates were higher in the Northeast region versus the South region for
      the majority of causes of death, including several noncommunicable conditions.
      CONCLUSIONS: Failure to adjust VR data for undercount of cases reported and
      misdiagnoses will cause underestimation of mortality risks for the populations of
      the Northeast region, which are more vulnerable than those in other regions of
      the country. In order to more reliably understand the pattern of disease, all
      cause-specific mortality rates in poor populations should be adjusted.

PMID- 22652967
TI  - [Evolution of consumption of high-cost drugs in Colombia].
AB  - OBJECTIVE: Determine the patterns of consumption of high-cost drugs (HCD) during
      the 2005-2010 period in a population of Colombian patients enrolled in the
      General System of Social Security in Health. METHODS: An observational
      descriptive study was conducted. The prescription data of formulas of any drug
      considered to be high-cost dispensed to all users (1 674 517) in 20 cities of
      Colombia between 2005 and 2010 were analyzed. The anatomical therapeutic
      classification was considered, and the number of patients as well as monthly
      invoicing for each drug, the daily dose defined, and the cost per 1 ;000
      inhabitants/day were defined. RESULTS: Over the entire study period, the amount
      invoiced for HCDs increased by 847.4%. Antineoplastic and immunomodulator drugs
      accounted for 46.3% of the total invoicing. The other drugs were anti-infectives
      (15.2%), systemic hormonal preparations (9.5%), and drugs for the nervous system
      (9.1%). Most of these drugs were prescribed at the daily doses defined as
      recommended by the World Health Organization, but with high costs per 1000
      inhabitants/day. CONCLUSIONS: In Colombia a crisis has occurred in recent years
      due to the high spending generated by the most expensive drugs. The progressive
      growth of pharmaceutical spending is greater than the increased coverage by the
      country's health system. The Colombian health system should evaluate how much it
      is willing to pay for the most expensive drugs for some diseases and what
      strategies should be implemented to cover these expenses and thus guarantee
      access to the insured.

PMID- 22652968
TI  - [Agroecology and health promotion in Brazil].
AB  - OBJECTIVE: Research how specialists in health promotion and agroecology
      understand the concepts in those areas of common guidelines and how the
      relationship between such concepts is conceived. METHODS. Qualitative research.
      Fourteen specialists in the two areas were interviewed about the relationship
      between the agrofood system and health, concepts of agroecology and health
      promotion, and the relevance of including agroecology in public health training
      courses and vice-versa. RESULTS: There is little dialogue between the fields of
      study that were considered similar, food quality being the main interface between
      the areas. agroecology appeared to be a system of healthy food production, but
      the study showed other connections: agroecology and empowerment, a spur to
      autonomy and quality of life, and better socioeconomic conditions for the farmer;
      agroecology and environmental health; agroecology and community involvement;
      agroecology, territoriality, and cultural rescue [translator's note: this is a
      term for measures taken to revitalize or preserve imperiled indigenous cultures];
      and agroecology, local foods, and low costs of production. Health promotion
      already was linked in effect to practices oriented to healthy lifestyles. The
      specialists appeared favorable toward including knowledge about public health in
      agroecology and vice-versa. CONCLUSIONS: Agroecology and health promotion
      contribute to one another and are complementary, and bringing them closer
      together can lead to an enriched discussion about rural health and the concept of
      public policies that focus on this theme, thereby stimulating actions for
      improvement and intersectoral practices.

PMID- 22652969
TI  - Lead exposure among children from native communities of the Peruvian Amazon
      basin.
AB  - OBJECTIVE: To assess potential risk factors associated with elevated blood lead
      levels (BLLs) among children in two communities from the Corrientes River basin
      in the Peruvian Amazon. METHODS: Children aged 0-17 years were screened for BLLs,
      hemoglobin levels, and anthropometric measures. Dwelling, family, and child data
      were collected through a parental questionnaire. Statistical analysis included
      descriptive and bivariate analysis. Multiple linear and logistic regressions
      using generalized estimating equations were also conducted to determine
      associated risk factors. A map of each community was drawn to examine the spatial
      distribution of BLLs. RESULTS: Of 208 children (88 from 23 households of the
      Peruanito community and 120 from 28 households of Santa Isabel), 27.4% had BLLs >
      10 ug/dL. The geometric mean (+/- standard deviation) BLL was 8.7 +/- 4.0 ug/dL
      (range 3.0-26.8 ug/dL). In the total population, linear regression analysis
      indicated that age was positively associated with BLLs (P < 0.05). Logistic
      regression analysis showed that boys had 2.12 times greater odds of having BLLs >
      10 ug/dL than girls (P < 0.05). Among the children 0-3 years, those whose mothers
      had BLLs > 10 ug/dL had 45.0% higher odds of presenting BLLs > 10 ug/dL than
      children whose mothers had BLLs < 10 ug/dL (P < 0.05). CONCLUSIONS: Older age,
      male gender, and mothers' BLL > 10 ug/dL were the main risk factors for elevated
      BLLs. The higher risk in boys 7-17 years suggests that exposure could be related
      to specific activities in this group, such as fishing and hunting. Continuous
      monitoring of BLLs in the Corrientes River population is recommended.

PMID- 22652971
TI  - [Out-of-pocket health spending: the case of Chile, 1997 and 2007].
AB  - OBJECTIVE: Determine the impact, characteristics, and changes in out-of-pocket
      health spending of households in Chile in 1997 and 2007. METHODS: A descriptive
      econometric study was conducted based on household surveys with cross-sectional
      information on spending in two years-1997 and 2007-for Greater Santiago. The
      evolution of indicators of per capita household spending by quintile was
      reviewed. The method proposed by the World Health Organization was used for
      econometric analysis of the determinants of out-of-pocket spending and
      catastrophic spending. The Gini indices were also calculated to analyze equity.
      RESULTS: Out-of-pocket health spending in the households of Greater Santiago
      increased significantly (39.5% per capita). The ratio of health spending in
      quintile 5 compared to quintile 1 decreased, but the increase in spending was
      less in quintile 5. In 2007, out-of-pocket spending was still determined by the
      presence of risk groups: under 5 years and, although to a lesser extent, over 65
      years of age. Catastrophic spending decreased slightly and the presence of older
      adults continues to increase this risk. The presence of women of childbearing age
      tends to minimize out-of-pocket spending. CONCLUSIONS: Out-of-pocket health
      spending in the households is high and has increased. It continues to have a
      significant influence on inequality. The effects of out-of-pocket spending
      containment programs such as AUGE are evident, but new financial protection
      policies that address the problem are needed.

PMID- 22652970
TI  - [Prevalence of grade retention and associated factors among adolescents from the
      1993 Pelotas, Brazil, birth cohort].
AB  - OBJECTIVE: To evaluate the occurrence of grade retention until 11 years of age
      and the factors associated with retention. METHODS: This prospective study
      included 4 452 adolescents from the 1993 city of Pelotas birth cohort (state of
      Rio Grande do Sul, Brazil). This sample represents 87.5% of the original cohort.
      Grade retention was defined as the repetition of at least one school grade until
      the date of the interview. The following independent variables were analyzed:
      sex, skin color, birth weight, ownership of goods, age, maternal schooling, type
      of school (private, state, or city), age at school entry, and employment.
      RESULTS: The overall frequency of grade retention was 36.3%, vs. 42.8% for boys
      and 30.0% for girls. The adjusted analysis showed that the lower the level of
      maternal schooling, ownership of goods, and birth weight, the higher the risk of
      grade retention for both boys and girls. Black/brown adolescents, those studying
      in public schools, and those who were 7 years of age or older at school entry had
      a higher risk of grade retention. For boys, childhood labor was associated with
      grade retention. CONCLUSIONS: Low socioeconomic and low maternal schooling levels
      were the factors most strongly associated with grade retention. Strategies to
      reduce this situation must take into account demographic and socioeconomic
      characteristics.

PMID- 22652972
TI  - Coronary heart disease mortality in China: age, gender, and urban-rural gaps
      during epidemiological transition.
AB  - OBJECTIVE: To examine and describe coronary heart disease (CHD) mortality and its
      pattern of change (trend) by sex, age, and area of residence (urban versus rural)
      in Tianjin, China, within the context of epidemiological transition, and compare
      it with current trends in the Americas and Europe. METHODS: A total of 104 393
      cases of CHD death in Tianjin occurring between 1999 and 2008 were monitored.
      Death due to CHD was coded using International Classification of Diseases (ICD)
      standards (ninth and tenth revisions). Standardized CHD mortality rates and their
      trends were analyzed by age, sex, and urban versus rural residence. RESULTS:
      During the 10-year study period, the proportion of total deaths due to CHD in
      Tianjin increased significantly (from 16% to 24%) and age-standardized CHD
      mortality increased slightly (with no statistical differences), in contrast to
      CHD mortality trends in various countries in the Americas and Europe, which are
      declining. No difference was found in Tianjin's CHD mortality trend by sex.
      Overall CHD mortality was consistently higher among older age groups, males, and
      residents of urban areas. The proportion of CHD deaths occurring outside
      hospitals was 55.81%, with a declining trend over the study period. Rural areas
      had a higher proportion of outside-hospital CHD mortality than urban areas, but
      no difference was found across age groups. CONCLUSIONS: From 1999 to 2008, CHD
      mortality in Tianjin varied by sex, age, and urban versus rural area of
      residence. Future research to identify CHD risk factors and the populations most
      vulnerable to the disease is recommended to help strengthen CHD prevention.
      Strategies for CHD control similar to those used in various developed countries
      in the Americas and Europe should be developed to reduce the CHD burden in China.

PMID- 22652973
TI  - [Economic benefits of the cochlear implant for treating profound sensorineural
      hearing loss].
AB  - OBJECTIVE: Evaluate the cost-benefit, cost-utility, and cost-effectiveness of
      cochlear implantation, comparing it to the use of hearing aids in children with
      profound bilateral sensorineural hearing loss. METHODS: The nonparametric
      propensity score matching method was used to carry out an economic and impact
      assessment of the cochlear implant and then perform cost-benefit, cost-utility,
      and cost-effectiveness analyses. Primary information was used, taken randomly
      from 100 patients: 62 who received cochlear implants (treatment group) and 38
      belonging to the control group who used hearing aids to treat profound
      sensorineural hearing loss. RESULTS: An economic cost differential was found-to
      the advantage of the cochlear implant-of close to US$ 204,000 between the implant
      and the use of hearing aids over the expected life span of the patients analyzed.
      This amount refers to the greater expenses that hearing-aid patients will have.
      With this adjusted figure, the cost-benefit indicator shows that for each dollar
      invested to treat the cochlear-implant patient, there is a return on the
      investment of US$ 2.07. CONCLUSIONS: The cochlear implant produces economic
      benefits for the patient. It also produces health utilities since positive cost
      utility (gain in decibels) and cost-effectiveness (gain in language
      discrimination) ratios were found.

PMID- 22652974
TI  - [Interventions to reduce salt consumption through labeling].
AB  - OBJECTIVE: Determine the extent to which labeling of food products informs about
      salt consumption. METHODS: A critical and systematic analysis was conducted of 9
      studies selected out of a total of 133 studies. The studies were collected by
      reviewing the scientific literature on interventions conducted in the human
      population aimed towards reducing salt consumption through label messaging. All
      of the information was obtained by direct consultation and by Internet from the
      scientific literature collected in several databases. RESULTS: Out of the 133
      articles recovered, after the inclusion and exclusion criteria were applied, 9
      studies were selected for review. All of them took into account the ability of
      the study population to interpret and understand salt content labeling in foods.
      CONCLUSIONS: Food consumers understand and value easily recognizable logos more
      than the information found on nutritional composition labels. Therefore, use of
      alternative logos that facilitate this information and are also standardized
      could be justified. This situation is reinforced because the inclusion of symbols
      that are easily understandable favors the most adequate choice by consumers.

PMID- 22652975
TI  - [Identification of ICF participation categories in quality-of-life instruments
      utilized in cerebrovascular accident victims].
AB  - OBJECTIVE: To identify the categories of the participation component of the
      International Classification of Functionality, Incapacity, and Health (ICF) which
      are currently related to Health-related Quality of Life (HRQOL) instruments
      commonly used in cerebrovascular accident (CVA) victims-Nottingham Health Profile
      (NHP), Short-Form Health Survey (SF-36), and Stroke Specific Quality of Life (SS
      QOL)-and suggest the utilization of these instruments to assess and/or
      characterize that component in that population. METHODS: Through searches in the
      Medline, SciELO, and Lilacs databases, a compilation of studies which associated
      the concepts measured by the NHP, SF-36, and SS-QOL items with the ICF components
      and categories, was carried out. RESULTS: Of the 24 identified studies, four met
      the established criteria: two assessed the three HRQOL instruments, one assessed
      the NHP and SF-36, and the other just the SS-QOL. For each instrument, three
      studies were found which associated their concepts up to, at least, the second
      hierarchical level of the ICF categories. Considering the results that were in
      agreement between the three studies that assessed the same instrument, nine
      participation categories were associated with the NHP, seven with the SF-36, and
      15 with the SS-QOL, although just one was specific to the NHP, one to the SF-36,
      and seven to the SS-QOL. CONCLUSIONS: To assess the participation of CVA victims
      based upon the ICF framework, the SS-QOL appeared to be the most suitable
      instrument in that, in addition to assessing the greatest number of categories,
      it also assesses the greatest number of distinct categories, when compared to the
      other two HRQOL instruments, which added just one category to those measured by
      SS-QOL.

PMID- 22652976
TI  - Medical equipment donations in Haiti: flaws in the donation process.
AB  - The magnitude 7.0 earthquake that struck Haiti on 12 January 2010 devastated the
      capital city of Port-au-Prince and the surrounding area. The area's hospitals
      suffered major structural damage and material losses. Project HOPE sought to
      rebuild the medical equipment and clinical engineering capacity of the country. A
      team of clinical engineers from the United States of America and Haiti conducted
      an inventory and assessment of medical equipment at seven public hospitals
      affected by the earthquake. The team found that only 28% of the equipment was
      working properly and in use for patient care; another 28% was working, but lay
      idle for technical reasons; 30% was not working, but repairable; and 14% was
      beyond repair. The proportion of equipment in each condition category was similar
      regardless of whether the equipment was present prior to the earthquake or was
      donated afterwards. This assessment points out the flaws that existed in the
      medical equipment donation process and reemphasizes the importance of the
      factors, as delineated by the World Health Organization more than a decade ago,
      that constitute a complete medical equipment donation.

PMID- 22652977
TI  - Cholera in Haiti's Artibonite Valley.

PMID- 22652978
TI  - Neptunium multipoles and resonant x-ray Bragg diffraction by neptunium dioxide
      (NpO2).
AB  - The low-temperature ordered state of neptunium dioxide (NpO(2)) remains
      enigmatic. After decades of experimental and theoretical efforts, long-range
      order of a time-odd (magnetic) high-order atomic multipole moment is now
      generally considered to be the fundamental order parameter, the most likely
      candidate being a magnetic triakontadipole (rank 5). To date, however, direct
      experimental observation of the primary order parameter remains outstanding. In
      the light of new experimental findings, we re-examine the effect of crystal
      symmetry on the atomic multipoles and the resulting x-ray resonant scattering
      signature. Our simulations use the crystallographic point group 3m (D(3d)),
      because corresponding magnetic groups 3m', 3'm', and 3'm are shown by us to be at
      odds with a wealth of experimental results. In addition to the previously
      observed (secondary) quadrupole order, we derive expressions for higher-order
      multipoles that might be observed in future experiments. In particular, magnetic
      octupole moments are predicted to contribute to Np M(2,3) and L(2,3) resonant
      scattering via E2-E2 events. The Lorentzian-squared lineshape observed at the
      M(4) resonance is shown to be the result of the anisotropy of the 3p(3/2) core
      levels. Quantitative comparison of our calculations to the measured data yields a
      core-hole width Gamma = 2.60(7) eV and a core-state exchange energy [absolute
      value]epsilon(1/2)[absolute value] = 0.76(2) eV.

PMID- 22652980
TI  - Synthetic approaches toward sesterterpenoids.
AB  - Sesterterpenoids account for many bioactive natural products, often with unusual
      and complex structural features, which makes them attractive targets for
      synthetic chemists. This review surveys efforts undertaken toward the synthesis
      of sesterterpenoids, focusing on completed total syntheses and covering ca. 50
      natural products in total.

PMID- 22652981
TI  - Absence of community-acquired methicillin-resistant Staphylococcus aureus
      carriage or infection in a cohort of 300 men who have sex with men attending an
      inner-city sexually transmitted disease clinic in Paris, France.
AB  - BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus
      (caMRSA) skin and soft-tissue infections are a major cause for concern.
      Communities of men who have sex with men (MSM) in the USA being prone to caMRSA
      epidemics, we investigated whether MSM attending our sexually transmitted disease
      clinic were carriers of or infected by caMRSA. METHODS: 300 MSM were
      prospectively recruited, interrogated and examined. Swabs of their nares and of
      their pubic and perineal skin were taken and cultured. RESULTS: No evidence of
      carriage or infection by caMRSA was found. Nasal carriage of methicillin
      sensitive S. aureus was within French estimates. Perineal carriage significantly
      correlated with the number of sexual partners. CONCLUSION: Although caMRSA
      carriage or infection does not seem to affect Paris MSM, prospective sampling may
      not be the best method to monitor them. The correlation between number of
      partners and perineal carriage suggests that thorough hygiene after intercourse
      could limit the spread of S. aureus in MSM with multiple partners.

PMID- 22652982
TI  - 82Rb PET/CT: entering a new area of myocardial perfusion imaging?

PMID- 22652979
TI  - Health and wellness technology use by historically underserved health consumers:
      systematic review.
AB  - BACKGROUND: The implementation of health technology is a national priority in the
      United States and widely discussed in the literature. However, literature about
      the use of this technology by historically underserved populations is limited.
      Information on culturally informed health and wellness technology and the use of
      these technologies to reduce health disparities facing historically underserved
      populations in the United States is sparse in the literature. OBJECTIVE: To
      examine ways in which technology is being used by historically underserved
      populations to decrease health disparities through facilitating or improving
      health care access and health and wellness outcomes. METHODS: We conducted a
      systematic review in four library databases (PubMed, PsycINFO, Web of Science,
      and Engineering Village) to investigate the use of technology by historically
      underserved populations. Search strings consisted of three topics (eg,
      technology, historically underserved populations, and health). RESULTS: A total
      of 424 search phrases applied in the four databases returned 16,108 papers. After
      review, 125 papers met the selection criteria. Within the selected papers, 30
      types of technology, 19 historically underserved groups, and 23 health issues
      were discussed. Further, almost half of the papers (62 papers) examined the use
      of technology to create effective and culturally informed interventions or
      educational tools. Finally, 12 evaluation techniques were used to assess the
      technology. CONCLUSIONS: While the reviewed studies show how technology can be
      used to positively affect the health of historically underserved populations, the
      technology must be tailored toward the intended population, as personally
      relevant and contextually situated health technology is more likely than broader
      technology to create behavior changes. Social media, cell phones, and videotapes
      are types of technology that should be used more often in the future. Further,
      culturally informed health information technology should be used more for chronic
      diseases and disease management, as it is an innovative way to provide holistic
      care and reminders to otherwise underserved populations. Additionally, design
      processes should be stated regularly so that best practices can be created.
      Finally, the evaluation process should be standardized to create a benchmark for
      culturally informed health information technology.

PMID- 22652983
TI  - Pathogen identification by nuclear imaging--almost there?

PMID- 22652984
TI  - A new nonsense mutation is associated with dysmorphism in lethal neonatal CPTII
      deficiency.

PMID- 22652986
TI  - Comparison of two methods for interpreting lifting performance during functional
      capacity evaluation.
AB  - BACKGROUND: Functional capacity evaluation (FCE) requires determination of effort
      by observation of effort indexes for performance interpretation. Waddell signs
      have been shown to be associated with decreased functional performance. Whether
      determination of effort by observational criteria and Waddell sign testing can be
      used interchangeably to interpret lifting performance is unknown. OBJECTIVE: The
      purposes of this study were to assess the concurrent validity of submaximal
      effort and Waddell signs and to determine whether these contribute independently
      to lifting performance. DESIGN: This investigation was an analytical cross
      sectional study. METHODS: A total of 130 people who had chronic nonspecific low
      back pain and were referred for fitness-for-work evaluation were included.
      Physical effort was determined on the basis of observational criteria for lifting
      from floor to waist, lifting from waist to shoulder, and horizontal lifting
      during FCE. A second assessor conducted Waddell sign testing. The concurrent
      validity of Waddell signs and submaximal effort was assessed by calculating
      sensitivity and specificity. Hierarchical regression analysis was used to
      determine the contributions of Waddell signs and submaximal effort to lifting
      performance. Age and sex were covariates. RESULTS: The FCE assessor found a low
      sensitivity of Waddell signs for submaximal effort determination. Between 53% and
      63% of the participants who were classified as showing submaximal effort had
      Waddell signs. Waddell signs and submaximal effort were independent contributors
      to lifting performance. The contribution of submaximal effort was larger than
      that of Waddell signs, as shown by 20% to 29% higher explained variance in
      lifting performance when submaximal effort was added to the model first versus 3%
      to 6% higher explained variance when Waddell signs were added first. LIMITATIONS:
      Assessor variability could have influenced the study results. CONCLUSIONS: In
      people with chronic nonspecific low back pain, Waddell sign testing and
      determination of physical effort by observational criteria should not be used
      interchangeably to interpret lifting performance during FCE.

PMID- 22652987
TI  - Safety and feasibility of an early mobilization program for patients with
      aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Survivors of aneurysmal subarachnoid hemorrhage (SAH) are faced with
      a complicated recovery, which typically includes surgery, prolonged monitoring in
      the intensive care unit, and treatment focusing on the prevention of
      complications. OBJECTIVE: The purpose of this study was to determine the safety
      and feasibility of an early mobilization program for patients with aneurysmal
      SAH. DESIGN: This study was a retrospective analysis. METHODS: Twenty-five
      patients received early mobilization by a physical therapist or an occupational
      therapist, or both, which focused on functional training and therapeutic exercise
      in more progressively upright positions. Participation criteria focused on
      neurologic and physiologic stability prior to the initiation of early
      mobilization program sessions. RESULTS: Patients met the criteria for
      participation in 86.1% of the early mobilization program sessions attempted.
      Patients did not meet criteria for the following reasons: Lindegaard ratio >3.0
      or middle cerebral artery (MCA) mean flow velocity (MFV) >120 cm/s (8.1%), mean
      arterial pressure (MAP) <80 mm Hg (1.8%), intracranial pressure (ICP) >15 mm Hg
      (1.8%), unable to open eyes in response to voice (0.9%), respiratory rate >40
      breaths/min (0.6%), MAP >110 mm Hg (0.3%), and heart rate <40 bpm (0.3%). Adverse
      events occurred in 5.9% of early mobilization program sessions for the following
      reasons: MAP <70 mm Hg (3.1%) or >120 mm Hg (2.4%) and heart rate >130 bpm
      (0.3%). The 30-day mortality rate for all patients was 0%. Participation in the
      early mobilization program began a mean of 3.2 days (SD=1.3) after aneurysmal
      SAH, and patients received an average of 11.4 sessions (SD=4.3). Patients
      required a mean of 5.4 days (SD=4.2) to participate in out-of-bed activity and a
      mean of 10.7 days (SD=6.2) to walk >=15.24 m (50 ft). CONCLUSIONS: The results of
      this study suggest that an early mobilization program for patients with
      aneurysmal SAH is safe and feasible.

PMID- 22652985
TI  - Relationship between intensity of quadriceps muscle neuromuscular electrical
      stimulation and strength recovery after total knee arthroplasty.
AB  - BACKGROUND: Neuromuscular electrical stimulation (NMES) can facilitate the
      recovery of quadriceps muscle strength after total knee arthroplasty (TKA), yet
      the optimal intensity (dosage) of NMES and its effect on strength after TKA have
      yet to be determined. OBJECTIVE: The primary objective of this study was to
      determine whether the intensity of NMES application was related to the recovery
      of quadriceps muscle strength early after TKA. A secondary objective was to
      quantify quadriceps muscle fatigue and activation immediately after NMES to guide
      decisions about the timing of NMES during rehabilitation sessions. DESIGN: This
      study was an observational experimental investigation. METHODS: Data were
      collected from 30 people who were 50 to 85 years of age and who received NMES
      after TKA. These people participated in a randomized controlled trial in which
      they received either standard rehabilitation or standard rehabilitation plus NMES
      to the quadriceps muscle to mitigate strength loss. For the NMES intervention
      group, NMES was applied 2 times per day at the maximal tolerable intensity for 15
      contractions beginning 48 hours after surgery over the first 6 weeks after TKA.
      Neuromuscular electrical stimulation training intensity and quadriceps muscle
      strength and activation were assessed before surgery and 3.5 and 6.5 weeks after
      TKA. RESULTS: At 3.5 weeks, there was a significant association between NMES
      training intensity and a change in quadriceps muscle strength (R(2)=.68) and
      activation (R(2)=.22). At 6.5 weeks, NMES training intensity was related to a
      change in strength (R(2)=.25) but not to a change in activation (R(2)=.00).
      Furthermore, quadriceps muscle fatigue occurred during NMES sessions at 3.5 and
      6.5 weeks, whereas quadriceps muscle activation did not change. LIMITATIONS: Some
      participants reached the maximal stimulator output during at least 1 treatment
      session and might have tolerated more stimulation. CONCLUSIONS: Higher NMES
      training intensities were associated with greater quadriceps muscle strength and
      activation after TKA.

PMID- 22652988
TI  - Dorsal column mapping for intramedullary spinal cord tumor resection decreases
      dorsal column dysfunction.
AB  - STUDY DESIGN: Retrospective cohort study and technical report. OBJECTIVE: To
      demonstrate, through our institutional series of intramedullary spinal tumor
      resection, the potential avoidance of dorsal column dysfunction after using
      dorsal column mapping. SUMMARY OF BACKGROUND DATA: Surgical resection of
      intramedullary spinal cord tumors carries significant associated postoperative
      morbidity. Much of this morbidity is because of dorsal column dysfunction from
      the dorsal myelotomy. The inconsistency and distortion of anatomic landmarks for
      a midline myelotomy has posed a significant challenge for spine surgeons. Dorsal
      column mapping is a relative new technique that may decrease the morbidity
      associated with operative resection of intramedullary masses. METHODS: A cohort
      of patients operated upon at our institution for intramedullary lesions were
      retrospectively reviewed. Neurologic examination changes were assessed through
      clinic notes and chart review. A total of 91 intramedullary tumors were assessed,
      with 80 patients without dorsal column mapping and 11 patients with dorsal column
      mapping. RESULTS: In our cohort of 91 patients with intramedullary tumors
      undergoing resection over the past decade, postoperative dorsal column
      dysfunction was observed in 45%. Dorsal column mapping decreased the frequency of
      new postoperative posterior column dysfunction. Patients with dorsal column
      mapping had a statistically significant decrease rate of new postoperative
      posterior column dysfunction of 9% compared with 50% for without mapping
      (P=0.01). Tumor histology was not found to correlate with worsening posterior
      column dysfunction in patients undergoing tumor resection. CONCLUSIONS: With our
      surgical cohort as an internal control, we found a decreased rate of
      postoperative posterior column dysfunction when using intraoperative dorsal
      column mapping. Our findings show the ability of this evolving technology to
      provide useful intraoperative information to localize the physiological midline
      and decrease the rate of posterior column dysfunction after intramedullary spinal
      cord tumor resection.

PMID- 22652989
TI  - Posterior facet load changes in adjacent segments due to moderate and severe
      degeneration in C5-C6 disc: a poroelastic C3-T1 finite element model study.
AB  - STUDY DESIGN: Biomechanics of normal vertebral segments adjacent to a degenerated
      segment in the cervical spine. OBJECTIVE: To test the hypothesis that posterior
      facet joints of adjacent segments are loaded more when degeneration occurs in the
      intermediate disc segment. SUMMARY OF BACKGROUND DATA: Degeneration progression
      in adjacent segments is a clinical concern. Literature studies that have
      documented the effects of a degenerated segment on the adjacent-segment discs
      have not addressed these effects on adjacent-segment posterior facets. Moreover,
      these biomechanical studies are performed mainly on the lumbar spine or the
      tissue quality of the cadavers is poor because of degenerated segments.
      Retrospectively, it is difficult to decipher to what extent degeneration in a
      single disc induces biomechanical changes in facet joints along the posterior
      spinal column. To date, no cervical spine biomechanical study investigated the
      facet joints response of adjacent segments when the disc in between those
      segments degenerates. METHODS: An earlier validated poroelastic, 3-dimensional
      finite element model of a normal C3-T1 segment was used. Two stages of
      degeneration (moderate and severe) were simulated in the C5-C6 disc. Disc
      geometry and tissue material properties were modified to simulate C5-C6 disc
      degeneration. For the 3 C3-T1 models, loads on the posterior facets at 3 levels
      (C4-C5, C5-C6, and C6-C7) were computed under moment loads. RESULTS: With
      progressive degeneration in the C5-C6 disc, posterior facet loading in adjacent
      segments and in the intermediate degenerated disc segment increased. Changes in
      facet loading in the inferior C6-C7 segment were greater than the corresponding
      changes in the superior C4-C5 segment. These changes were highest in lateral
      bending and lowest in axial rotation. CONCLUSIONS: Higher changes in facet loads
      along the posterior spinal column may contribute to altered biomechanics in
      neighboring segments. Future biomechanical experiments are required to develop a
      more clear understanding of the posterior facet joints response in neighboring
      segments because of degeneration in a cervical disc.

PMID- 22652991
TI  - The prevalence and severity of lumbar spine motion impairment in normal subjects.
AB  - STUDY DESIGN: Crosssectional. OBJECTIVE: To assess the prevalence and severity of
      lumbar spine motion impairment in normal subjects. SUMMARY OF BACKGROUND DATA: A
      prior study of cervical and lumbar spine impairment indicated that a high
      percentage of normal subjects had impairment. METHODS: A total of 579 normal
      subjects were assessed for lumbar spine motion impairment using 3 editions (Third
      Edition Revised, Fourth Edition, and Fifth Edition) of the American Medical
      Association Guides to the Evaluation of Permanent Impairment (AMA Guides).
      RESULTS: Eighty percent to 86% of normal subjects had impairment due to loss of
      lumbar motion. CONCLUSIONS: A high percentage of normal subjects will have lumbar
      spine impairment due to loss of lumbar motion using the AMA Guides.

PMID- 22652990
TI  - Fluoroscopic caudal epidural injections with or without steroids in managing pain
      of lumbar spinal stenosis: one-year results of randomized, double-blind, active
      controlled trial.
AB  - STUDY DESIGN: A randomized, double-blind, active-controlled trial. OBJECTIVE: To
      evaluate the effectiveness of caudal epidural injections with or without steroids
      in providing effective and long-lasting pain relief in the management of chronic
      low back pain related to lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA:
      Multiple interventions including surgery and interventional techniques such as
      epidural injections and adhesiolysis are commonly performed in managing pain
      related to spinal stenosis. There is continuing debate on the effectiveness of
      all interventions, and a paucity of literature regarding effectiveness. METHODS:
      One-hundred participants were randomly assigned to 1 of the 2 groups, with Group
      I participants receiving caudal epidural injections of local anesthetic
      (lidocaine 0.5%), whereas Group II participants received caudal epidural
      injections with 0.5% lidocaine 9 mL mixed with 1 mL of steroid (nonparticulate
      Celestone). OUTCOMES ASSESSMENT: Multiple outcome measures were used, including
      the Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI),
      employment status, and opioid intake with assessment at 3, 6, and 12 months
      posttreatment. Significant pain relief and improvement in disability were defined
      as 50% or more. RESULTS: Overall, significant pain relief and functional status
      improvement (>=50%) were demonstrated in 48% in Group I and 46% in Group II.
      However, significant pain relief and functional status improvement were seen in
      60% of the participants in both groups in the successful category when the
      participants were separated into successful and failed categories. The overall
      number of procedures was 3.1+/-1.3 or 3.6+/-1.1 in the successful category in
      Group I, with overall 2.9+/-1.4 or 3.5+/-1.2 in the successful category in Group
      II. CONCLUSION: Caudal epidural injections of local anesthetic with or without
      steroids may be an effective treatment for a select group of patients with
      chronic function-limiting low back and lower extremity pain secondary to spinal
      stenosis.

PMID- 22652992
TI  - The challenge of using gene- or cell-based therapies to treat lung disease.

PMID- 22652993
TI  - It's time to end RAC review of gene therapy protocols.

PMID- 22652996
TI  - Challenges in vector and trial design using retroviral vectors for long-term gene
      correction in hematopoietic stem cell gene therapy.

PMID- 22652997
TI  - Novel therapies, high-risk pediatric research, and the prospect of benefit:
      learning from the ethical disagreements.

PMID- 22652998
TI  - Myocardial repair and regeneration: bone marrow or cardiac stem cells?

PMID- 22653001
TI  - Strong non-linear effects in the chiroptical properties of the ligand-exchanged
      Au38 and Au40 clusters.
AB  - Ligand exchange reactions on size-selected Au(38)(2-PET)(24) and Au(40)(2
      PET)(24) clusters (2-PET: 2-phenylethylthiol) with mono- and bi-dentate chiral
      thiols were performed. The reactions were monitored with MALDI mass spectrometry
      and the arising chiroptical properties were compared to the number of
      incorporated chiral ligands. Only a small fraction of chiral ligands is needed to
      induce significant optical activity to the clusters. The use of bidentate 1,1'
      binaphthyl-2,2'-dithiol (BINAS) leads to slow exchange, but the optical activity
      measured is strong. Moreover, a non-linear behaviour between optical activity and
      the number of chiral ligands is found in the BINAS case for both Au(38) and
      Au(40), which may indicate different exchange rates of enantiopure BINAS with the
      enantiomers of inherently chiral (but racemic) clusters. This is ascribed to
      effects arising from the bidentate nature of BINAS. In contrast, the use of
      monodentate camphor-10-thiol (CamSH) leads to comparably fast exchange on both
      clusters. The arising optical activity is weak. This is the first study where
      chiroptical effects are directly correlated with the composition of the ligand
      shell.

PMID- 22652999
TI  - Advances in foamy virus vector technology and disease correction could speed the
      path to clinical application.

PMID- 22653003
TI  - Contact dermatitis in military personnel.
AB  - Military personnel encounter the same allergens and irritants as their civilian
      counterparts and are just as likely to develop contact dermatitis from common
      exposures encountered in everyday life. In addition, they face some unique
      exposures that can be difficult to avoid owing to their occupational duties.
      Contact dermatitis can be detrimental to a military member's career if he or she
      is unable to perform core duties or avoid the inciting substances. An
      uncontrolled contact dermatitis can result in the member's being placed on
      limited-duty (ie, nondeployable) status, needing a job or rate change, or
      separation from military service. We present some common causes of contact
      dermatitis in military personnel worldwide and some novel sources of contact
      dermatitis in this population that may not be intuitive.

PMID- 22653004
TI  - "Eczemas" and leptin.
AB  - BACKGROUND: Leptin belongs to the helical cytokine family and has structural
      similarity to interleukin (IL)-6, IL-12, IL-15, prolactin, and growth hormone. It
      is mainly secreted by adipocytes but (at lower levels) also by stomach, skeletal
      muscle, and placenta. Initially, leptin was considered an antiobesity hormone,
      but experimental evidence has also shown pleiotropic effects on hematopoiesis,
      angiogenesis, lymphoid organ homeostasis, and T-lymphocyte functions. Recent
      evidence indicates that leptin modifies T-cell immunity by promoting T helper 1
      proinflammatory immune response and production of cytokines. OBJECTIVE: The aim
      of the present study was to evaluate leptin serum levels in patients with
      allergic contact dermatitis (ACD) and atopic dermatitis and to evaluate the
      correlation of these levels with different patterns of lymphocyte subpopulations.
      METHODS: Serum leptin was assayed by enzyme-linked immunosorbent assay.
      Immunophenotypic analysis of peripheral blood was performed by flow cytometry.
      RESULTS: We found that serum leptin levels were higher in ACD patients than in
      healthy controls (p = .02). In these patients, an inverse correlation between
      serum leptin and the percentage of CD4CD25 T lymphocytes was observed (p = .002).
      CONCLUSION: These data seem to suggest that leptin might play a role in the
      pathogenesis of ACD and thus have implications for the therapy for ACD.

PMID- 22653005
TI  - Prevalence of contact allergy at a dermatology clinic in China from 1990-2009.
AB  - BACKGROUND: The prevalence of contact allergy varies in different regions and
      populations. OBJECTIVE: To describe the frequency of sensitization in patients
      with dermatitis or eczema referred to Peking University First Hospital and
      analyze the trends in the prevalence of common allergens from January 1, 1990, to
      December 31, 2009. METHODS: A total of 1,858 patients were patch tested with the
      Chinese baseline series of contact allergens. Data were collected from
      retrospective charts and analyzed. RESULTS: Positive reactions to one or more
      allergens were shown in 1,374 patients (74.0%). The most common sensitizers were
      nickel sulfate (25.7%), fragrance mix I (25.6%), thiuram mix (25.5%), ammoniated
      mercury (20.5%), and p-phenylenediamine (19.1%). A statistically significant
      increase of sensitization over the 20-year period was seen for nickel sulfate,
      fragrance mix, ammoniated mercury, colophony, ethylenediamine, and potassium
      dichromate. Mercapto mix showed a trend of a statistically significant decrease
      in sensitizations from 1990 to 2009. CONCLUSIONS: The patterns of contact allergy
      in patients from Peking University Hospital are different from those of patients
      in other regions of China, in European countries, and in the United States.
      Nickel and fragrance mix were the most common allergens, and the sensitization
      rates of these two allergens had been increasing remarkably during the 20 years
      from 1990 to 2009.

PMID- 22653006
TI  - A 10-year review of p-phenylenediamine allergy and related para-amino compounds
      at the Ottawa Patch Test Clinic.
AB  - BACKGROUND: p-Phenylenediamine (PPD) is an important allergen; 5.0% of patients
      tested positive to PPD when patch-tested, according to the North American Contact
      Dermatitis Group. Hair dyes are the main source of exposure. OBJECTIVE: To assess
      the significance of PPD allergy at the Ottawa Patch Test Clinic. METHODS: We
      assessed the epidemiology of PPD allergies and determined the cross-reactivity
      with other para-amino compounds. Charts of patients visiting the Ottawa Patch
      Test Clinic between May 1997 and July 2009 were reviewed. RESULTS: One hundred
      thirty-four patients were found to have a contact allergy to PPD; 75.4% were
      female, 24.6% were male, 13.4% were hairdressers, 18.7% had a history of atopy,
      90.3% were sensitized by hair dye, 2.2% were sensitized by henna tattoos, and
      7.5% were sensitized by other sources. Positive patch-test reactions to textile
      dyes were seen in 24.6%, 7.5% reacted to benzocaine, 6.0% reacted to sulfa drugs,
      1.5% reacted to isopropyl-para-phenylenediamine, and 1.5% reacted to para
      aminobenzoic acid. CONCLUSIONS: PPD is an important source of allergic contact
      allergy. Our results show a significant relationship of PPD with other related
      para-amino compounds.

PMID- 22653007
TI  - Textile dyes Disperse Orange 1 and Yellow 3 contain more than one allergen as
      shown by patch testing with thin-layer chromatograms.
AB  - BACKGROUND: It is known that some patch-test preparations containing disperse
      dyes contain impurities with unknown relevance for the development or elicitation
      of contact allergy. OBJECTIVE: To evaluate the significance of the impurities
      found in the commercial dyes Disperse Orange 1 (DO1) and Disperse Yellow 3 (DY3)
      regarding contact allergy in patients with known sensitivity to them. METHODS:
      Ten patients allergic to DY3 and/or DO1 were tested with a dilution series of
      commercial and purified DY3 and DO1 (with water-soluble parts prepared from the
      commercial dyes) and with naphthalene sulfonate. Nine patients were additionally
      tested with thin-layer chromatograms (TLCs) made from the commercial DO1 and DY3
      and with paper chromatograms made from the water-soluble part of these dyes.
      RESULTS: Eight of nine and three of six patients tested positively to the TLCs of
      DO1 and DY3, respectively. Among them, 4 of 8 and 2 of 3 patients, respectively,
      were positive also to another spot on the TLCs. One patient was positive to the
      paper chromatogram from the water-soluble part of DO1. None of the tested
      patients reacted to naphthalene sulfonate. CONCLUSION: The results of our study
      suggest that there are more relevant allergens in the fat-soluble and water
      soluble fractions of the commercial disperse dyes.

PMID- 22653008
TI  - Lavender.
AB  - Lavender is a commonly used product in personal and household care items as well
      as for aromatherapy. It is increasing in popularity as a fragrance. Additionally,
      multiple recent publications attest to its antimicrobial activity. Whereas
      lavender has been associated with irritant dermatitis, allergic contact
      dermatitis, and photodermatitis, it is anticipated that with increasing exposure,
      more patients will experience these complications. Most cases of allergic contact
      dermatitis have been reported as being due to occupational exposures through
      massage and aromatherapy. One study of the Japanese population demonstrated an
      increased incidence of contact dermatitis from lavender (from 1.1% to 13.9% over
      8 years). It is important that clinicians recognize lavender as a potential
      allergen.

PMID- 22653009
TI  - Allergic contact dermatitis from carmine in cosmetic blush.
AB  - Although there are many reported cases of immediate allergy after ingestion of
      foods containing cochineal, there are few reports of allergic contact dermatitis
      from carmine. We present a rare case of allergic contact dermatitis due to
      carmine. A 52-year-old female presented with an itchy erythema on her cheeks at
      the site where blush had been applied. Patch-tested with her cosmetics, she
      showed a positive reaction to the blush (30% in petrolatum) and to 0.2% (but not
      0.1%) carmine in petrolatum. In this case, the optimum patch-test concentration
      of carmine was 0.2% in petrolatum.

PMID- 22653010
TI  - Ear dermatitis + epoxy reactivity = hearing aid allergy?

PMID- 22653011
TI  - Alcohol urticaria syndrome.

PMID- 22653012
TI  - Dermatitis induced by estrogen and progesterone: dual positive results on the
      intradermal skin test.

PMID- 22653013
TI  - Unusual localization of allergic contact dermatitis from p-phenylenediamine.

PMID- 22653014
TI  - Intertriginous and flexural exanthema after application of a topical anesthetic
      cream: a case of baboon syndrome.

PMID- 22653016
TI  - [Epidemiology of osteoporosis in Japan].
AB  - The high prevalence and tragic consequences of related fractures make
      osteoporosis a major burden on modern society. According to population-based
      epidemiologic studies, the estimated number of people with osteoporosis in Japan
      is 15 million, and only 20% of them are under treatment. Osteoporosis is a highly
      undertreated disease.  The most recent incidence rates of hip fracture in Japan
      were 5.1 in 10,000 men and 18.1 in 10,000 women in 2007, and the number of
      patients are approximately 130 thousands which are 2.8-fold higher than those of
      the initial survey of 1987, but are still substantially less than rates in
      Caucasian populations. This increase in incidence rates can be explained by an
      increase in the elderly population.  Data on the prevalence and incidence of
      vertebral fractures in Japan are vague compared with those of hip fracture.
      Prevalence rate of vertebral fracture was reported to be comparable to those in
      Caucasian populations, or even higher, and is approximately 30% in women aged 70s
      and 40% in those aged 80s.  Hip fracture increases the mortality risk by
      approximately 10% or 20% during one year after the index fracture. Functional
      level of patients with hip fracture is deteriorated in 60% of them compared with
      pre-fracture level. Vertebral fracture also increases the risk of mortality even
      in radiographically determined ones.  We currently have 13 million patients with
      osteoporosis in Japan among whom 130 thousands are suffered from hip fracture
      every year among whom 20 thousands die and 60 thousands experience functional
      decline. Effective preventive and therapeutic measures for osteoporosis should be
      conducted in more efficient ways. A greater role of the new guideline is expected
      than ever to promote preventive measures against osteoporosis and to increase
      physician's awareness to this disease.

PMID- 22653017
TI  - [Etiology of osteoporosis -decrease of bone mineral density and deterioration of
      bone quality-].
AB  - In osteoporosis, the risk of fracture is influenced by decrease of bone mineral
      density and deterioration of bone quality. The latter includes deterioration of
      the material and structural properties of bone. These changes arise from the
      influence of changes in hormonal balance, aging, changes in mechanical stress,
      lifestyle-related diseases, etc. on bone absorption and bone formation as the
      coupled functions of osteoclasts and osteoblasts. Deterioration of bone quality
      occurs at various levels ranging from the molecular to the tissue level, or even
      at the individual level, and leads to an increased fracture risk. Evaluating
      fracture risk on the basis of a sound understanding of the various etiologies of
      osteoporosis is important when treating osteoporosis.

PMID- 22653018
TI  - [Osteoporosis secondary to various disorders].
AB  - Secondary osteoporosis is caused by various disorders, metabolic derangements,
      and drug administration. Among causative disorders, primary hyperparathyroidism,
      rheumatoid arthritis, type 2 diabetes mellitus, and chronic kidney disease are
      prevalent ones. Fractures in type 2 diabetes and chronic kidney disease tend to
      result from the reduction in bone quality rather than that in bone mass.

PMID- 22653019
TI  - [Development and application of fracture risk assessments].
AB  - Definition of osteoporosis by BMD T-score has been accepted globally. However,
      the age-dependent changes in BMD values differ on the different sites for
      measurements and the sensitivity of BMD to predict the risk of osteoporotic
      fracture, assessed by the risk gradient value, is as small as 1.7. Reportedly,
      WHO Fracture Risk Assessment (FRAX(r)) tool to compute 10-year probabilities of
      osteoporotic fracture, is sensitive enough to select the high fracture risk
      subjects with the risk gradient value of 2.57 - 2.77 in Japanese men and women.
      The combination of the three major risk factors such as age, BMD and prevalent
      fractures, when both morphometric spine and clinical non-spine fracture are
      included, represents the value of 2.49 - 2.71. Radiographic assessment of
      prevalent vertebral fracture, along with FRAX(r)evaluation, seems to be important
      in assessing the fracture risk in Japanese subjects.

PMID- 22653020
TI  - [Prevention of osteoporosis].
AB  - Of all interventions for osteoporosis as an overt lifestyle-related disease,
      primary prevention is given first priority, where gaining beneficial lifestyle
      habits during younger years leads to acquisition of maximum bone mass.  Clear
      increases in bone mass are seen before the age of 18 years, with the increases
      being most conspicuous from 10 to 14 years of age, the time of onset of menarche,
      during which, for individuals in adequate nutritional status, vertical load
      exercises are the most efficient of all approaches in ensuring acquisition of
      maximum bone mass.  After the young adult mean (YAM) has been attained between 20
      and 44 years, the focus in primary prevention is shifted to prevention of bone
      mass decreases, in which high bone mass acquired through beneficial diet and
      exercise habits during younger years helps to delay the onset of osteoporosis
      even in advanced age.

PMID- 22653021
TI  - [Diagnosis of osteoporotic fracture].
AB  - The concept and terminology for bone fractures is now in some confusion between
      two academic fields, one of osteoporosis and the other of orthopedic fracture
      treatment, concerning the treatment of osteoporosis and the prevention of
      fragility fractures. In the former field, the terms of "incident or prevalent"
      fracture are commonly used ; by contrast, bone fracture simply means "fresh"
      fracture in the latter. Used to be based of X-ray films, diagnosis of
      osteoporotic fracture are now changing to depend on MRI, because its sensitivity
      and specificity of detecting fresh fracture of vertebral body is far better than
      other methods.

PMID- 22653022
TI  - [Significance of marker for bone metabolism].
AB  - The measurement of biochemical markers for bone metabolism is officially approved
      in clinical practice for osteoporosis in Japan for the purpose of assessment of
      bone metabolism and thus for rational selection of anti-osteoporotic drug and the
      early determination of its effect. In 2011 version of guideline for protection
      and treatment for osteoporosis and 2012 version of guideline for bone metabolic
      marker, the novel marker, such as P1NP, which responds precisely to newly
      approved PTH (1-34) with bone-formation stimulating effect was focused.
      Furthermore, the effect of renal dysfunction on the markers which were secreted
      into urine was also emphasized because of the apparent increases in their serum
      levels independent of bone metabolic state.

PMID- 22653023
TI  - [QOL evaluation for osteoporosis].
AB  - It is important to evaluate the Health Related QOL (HRQOL) in the treatment of
      the patients with osteoporosis. In 1999, the Japanese Society for Bone and
      Mineral Research made Japanese Osteoporosis Quality of Life Questionnaire (JOQOL)
      to evaluate the osteoporosis specific HRQOL of the Japanese patients. This JOQOL
      1999-version was revised in 2000. JOQOL 2001 version consists of six domain 38
      items, using five-point scale ranging from 0 to 4, scored from 0 to 152.  
      Osteoporosis is a bone disorder with decreased bone strength, resulting in bone
      fragility and consequently fractures. The vertebral fractures cause a change in
      the spinal column (kyphosis) and the decline of the physical function due to the
      back pain. This is the decrease in QOL of the patients with osteoporosis compared
      to cases without osteoporosis. Therefore, assessment of QOL are recommended in
      the prevention and treatment for osteoporosis.

PMID- 22653024
TI  - [Assessment of fall risk and fall prevention].
AB  - Typical risk factors for falls include a history of falling, decreased walking
      ability, and taking certain drugs. Serum vitamin D concentration is associated
      with falls, and vitamin D administration decreases falls. Fall prevention methods
      include exercise intervention, interventions other than exercise, and
      multifaceted interventions. However, the scientific evidence for whether fall
      prevention prevents fractures is poor. Fracture prevention with the use of hip
      protectors is effective in nursing facility dwellers, but not in elderly people
      living at home.

PMID- 22653025
TI  - [Clinical application of FRAX(r) in Japan].
AB  - FRAX(r) is a fracture risk assessment tool developed by WHO working groups. Ten
      year risks for major osteoporotic fractures or hip fracture can be calculated
      with FRAX(r). It has been discussed how to utilize FRAX(r) in the clinical
      settings in Japan. It was necessary to recognize the performance and limitation
      of this tool. In the Japanese guideline for prevention and treatment of
      osteoporosis 2011, a threshold of 10-year risk for major osteoporotic risk was
      proposed for the patients with osteopenia. It is emphasized that this is the
      proposal to use FRAX(r) in addition to the result of bone mineral density
      measurement and is not the proposal to use FRAX(r) as a screening tool. The way
      to utilize FRAX(r) as a screening tool should be investigated further.

PMID- 22653026
TI  - [Many issues about bone quality].
AB  - According to the present definition of osteoporosis, bone mineral density,
      architecture, and tissue material properties are important factors in determining
      bone strength. Bone matrix consists of a two-phase composite material in which
      the mineral phase provides stiffness and collagen provide tensile strength and
      ductility. The proposed determinants of bone strength at the material level are
      the degree of mineralization of basic structure units, microdamage accumulation,
      and collagen cross-link formation. These are regulated by cellular activities,
      tissue turnover rate, and the levels of oxidative stress and glycation. In this
      review, I describe the concerns regarding bone qualities.

PMID- 22653027
TI  - [New approved drugs for osteoporosis in Japan].
AB  - These 2 years, we had had new therapeutic options for osteoporotic patients, for
      example minodoronate, bazedoxifene, teriparatide and eldecalcitol in Japan.
      Minodoronate and eldecalcitol came from Japan and they had many clinical
      evidences on Japanese patients. Teriparatide is a powerful anabolic agent for
      bone, had been provided as daily or weekly subcutaneous injection. These reagents
      may become helpful drug for osteoporotic patients. This review shows the
      character and clinical evidences of these drugs.

PMID- 22653028
TI  - [New approved markers of bone turnover for osteoporosis in Japan].
AB  - Various markers of bone turnover are already under clinical use in Japan, and
      mostly for clinical investigation in some countries. Standard values including
      ranges and variations are summarized in the previous edition of the guideline.
      The information of additional new markers adapted by government is summarized
      including clinical features in the new edition 2012. Among the new markers, the
      methods for measurement for TRACP-5b and ucOC are developed in Japan. As P1NP and
      TRACP-5b levels are not affected by meals, biological variations are smaller
      compared with other markers. ucOC is unique because it is to evaluate vitamin K
      insufficiency for bone. New bone markers adapted in the Japanese guideline 2012
      will facilitate clinicians to utilize of metabolic markers of bone for
      osteoporosis treatment.

PMID- 22653029
TI  - [Therapeutic purpose and treatment guideline of osteoporosis].
AB  - The purpose of osteoporosis treatment is mainly for maintenance of bone health
      and QOL as well as for fracture prevention, and pharmacological intervention,
      improvement of risk factors including lifestyle, utilization of FRAX(r) are
      important in practice. Recently, treatment guideline of osteoporosis is revised
      in the Japanese guidelines for the prevention and treatment of osteoporosis.

PMID- 22653030
TI  - [Evaluation methods of therapeutic effects of drugs for osteoporosis].
AB  - "The guideline for prevention and treatment of osteoporosis 2011" shows methods
      and precautions for evaluations of therapeutic effects of drugs for osteoporosis,
      in terms of bone mineral measurements, bone turnover markers, and vertebral
      deformities and fractures. Bone mineral measurements are effective, but
      responsible for just some part of the observed reduction in the risk of vertebral
      fracture. Bone turnover markers enable early and easy evaluations for the
      effectiveness of drugs, such as bone-resorption inhibitors or bone-formation
      accelerators. In particular, TRACP-5b and P1NP are user-friendly, because of
      small daily and day-to-day variations, as well as large amount of changes with
      therapy. SQ methods are well designed for X-ray evaluations of vertebral
      deformities and fractures with high convenience and reproducibility, good for not
      only epidemiological study, but daily practice.

PMID- 22653031
TI  - [Anti-osteoporosis drugs : their characteristics and evidence for anti-fracture
      efficacy].
AB  - Remarkable progress in development of anti-fracture drugs has been achieved. Now
      we have anti-resorptive drugs, bisphosphonates and selective estrogen receptor
      modulators (SERMs) , bone anabolic one, teriparatide, and active vitamin D(3)
      analogues, alfacalcidol and eldecalcitol. Accumulating evidence shows their anti
      fracture efficacy and safety profiles. We should learn fundamental evidence of
      those medicines as prescribing them to patients with osteoporosis.

PMID- 22653032
TI  - [Concomitant treatment of the osteoporotic drugs].
AB  - Osteoporotic drugs are classified to 3 categories ; anti-resorptives,
      supplemental and anabolic drugs. A lot of evidence has been made about each
      osteoporotic drug. Although concomitant drug subscriptions are often used by many
      physicians, little evidence has been ever made about the concomitant drug
      treatment. Theoretically different categorized drugs should be combined in
      concomitant treatment. Fragility fracture risks have been tested compared
      alendronate (Aln) mono-therapy and Aln + alfacalcidol (VD(3)) for 2 year in
      JOINT02 of ATOP study. Aln + alfacalcidol (VD(3)) concomitant treatment has
      significantly reduced vertebral fracture risk compared with Aln mono-therapy in
      patients with advanced osteoporosis with multiple and high SQ grade vertebral
      fracture and also reduced weight bearing bone fracture risk.

PMID- 22653033
TI  - [Is SSBT associated with atypical femoral fracture? SSBT is associated with
      atypical femoral fracture - pathophysiology of atypical femoral fractures - ].
AB  - Recently, atypical femoral fracture has emerged as potential complication of long
      term bisphosphonate therapy. Before considering the potential harmful effects of
      oversupression of bone turnover, it has been supposed that suppressed bone
      turnover in postmenopausal skeleton has well documented beneficial effects on
      bone strength and fracture risk. However, the benefit of long-term use of
      bisphosphonate for the prevention of femoral fractures seems to be lower than
      previously speculated. There are several factors by which severely suppressed
      bone turnover may reduce bone mechanical properties. These include increased
      mineralization of bone and increased homogeneity of mineralization, changes in
      collagen cross linking and accumulation of bone microdamage.

PMID- 22653034
TI  - [Is SSBT associated with atypical femoral fracture? SSBT isn't associated with
      atypical femoral fracture].
AB  - Recent studies indicating a relationship between duration of bisphosphonate
      therapy and risk of atypical femoral fractures, together with epidemiological
      data demonstrating divergent trends in hip versus subtrochanteric fracture
      incidence, support the contention that there is an association between
      bisphosphonate therapy and atypical femoral fractures. However, although there
      are biologically plausible mechanisms by which bisphosphonates may impair bone
      strength, a direct causal association has yet to be established. The vast
      majority of patients treated with bisphosphonates do not develop atypical femoral
      fractures despite suppressed bone turnover, and, moreover, there is no evidence
      that suppression is greater in those with than without atypical fractures.
      Current evidence suggests that bisphosphonates, whilst not a prerequisite for the
      development of atypical femoral fractures, may contribute to their development in
      some cases. Identification of the factors that predispose individuals to develop
      these rare fractures may hold the key to uncovering their pathophysiology. The
      benefits of bisphosphonates use outweigh the risks.

PMID- 22653035
TI  - Identification in an anaerobic batch system: global sensitivity analysis, multi
      start strategy and optimization criterion selection.
AB  - Several mathematical models have been developed in anaerobic digestion systems
      and a variety of methods have been used for parameter estimation and model
      validation. However, structural and parametric identifiability questions are
      relatively seldom addressed in the reported AD modeling studies. This paper
      presents a 3-step procedure for the reliable estimation of a set of kinetic and
      stoichiometric parameters in a simplified model of the anaerobic digestion
      process. This procedure includes the application of global sensitivity analysis,
      which allows to evaluate the interaction among the identified parameters, multi
      start strategy that gives a picture of the possible local minima and the
      selection of optimization criteria or cost functions. This procedure is applied
      to the experimental data collected from a lab-scale sequencing batch reactor. Two
      kinetic parameters and two stoichiometric coefficients are estimated and their
      accuracy was also determined. The classical least-squares cost function appears
      to be the best choice in this case study.

PMID- 22653036
TI  - Metabolic pathway analysis and kinetic studies for production of nattokinase in
      Bacillus subtilis.
AB  - We have constructed a reaction network model of Bacillus subtilis. The model was
      analyzed using a pathway analysis tool called elementary mode analysis (EMA). The
      analysis tool was used to study the network capabilities and the possible effects
      of altered culturing conditions on the production of a fibrinolytic enzyme,
      nattokinase (NK) by B. subtilis. Based on all existing metabolic pathways, the
      maximum theoretical yield for NK synthesis in B. subtilis under different
      substrates and oxygen availability was predicted and the optimal culturing
      condition for NK production was identified. To confirm model predictions,
      experiments were conducted by testing these culture conditions for their
      influence on NK activity. The optimal culturing conditions were then applied to
      batch fermentation, resulting in high NK activity. The EMA approach was also
      applied for engineering B. subtilis metabolism towards the most efficient pathway
      for NK synthesis by identifying target genes for deletion and overexpression that
      enable the cell to produce NK at the maximum theoretical yield. The consistency
      between experiments and model predictions proves the feasibility of EMA being
      used to rationally design culture conditions and genetic manipulations for the
      efficient production of desired products.

PMID- 22653037
TI  - Autophagy genes promote apoptotic cell corpse clearance.
AB  - Autophagy is a catabolic process through which damaged organelles and protein
      aggregates are delivered to lysosomes for degradation. Autophagy genes are
      reported to promote exposure of "eat me" signals on the surface of apoptotic
      cells, but whether they function in engulfing cells is not clear. Recently, we
      found that the autophagy mutants atg-18 and epg-5 are defective in removing
      apoptotic cells derived from the C. elegans Q neuroblast, a phenotype that can be
      fully rescued by expression of ATG-18 and EPG-5 in the engulfing cell. Loss of
      ATG-18 or EPG-5 does not affect cell corpse engulfment but causes defects in
      phagosomal recruitment of RAB-5 and RAB-7 and formation of phagolysosomes. EPG-5,
      ATG-18 and LGG-1 are sequentially recruited to phagosomes, suggesting that they
      function at different steps of phagosomal maturation. Our studies indicate that
      autophagy genes function sequentially to promote apoptotic cell corpse
      degradation in the engulfing cell.

PMID- 22653038
TI  - Gold nanorods as nanotransducers to monitor the growth and swelling of ultrathin
      polymer films.
AB  - In this work, we demonstrate that plasmonic nanostructures can be employed as
      nanoscale transducers to monitor the growth and phase transitions in ultrathin
      polymer films. In particular, gold nanorods with high refractive index
      sensitivity (~150 nm/refractive index unit (RIU)) were employed to probe the
      growth and swelling of polyelectrolyte multilayers (PEM). By comparing the
      wavelength shift and extinction intensity increase of the localized surface
      plasmon resonance (LSPR) of the gold nanorods coated with PEM in air and water,
      the swelling of PEM was estimated to be 26% +/- 6%. The swelling was
      quantitatively confirmed with independent thickness measurement of PEM in dry and
      swollen states using AFM. The deployment of shape-controlled metal nanostructures
      with high refractive index sensitivity represents a novel and facile approach for
      monitoring the phase transition in polymers with nanoscale resolution.

PMID- 22653039
TI  - Analytical GIAO and hybrid-basis integral derivatives: application to geometry
      optimization of molecules in strong magnetic fields.
AB  - Analytical integral evaluation is a central task of modern quantum chemistry.
      Here we present a general method for evaluating differentiated integrals over
      standard Gaussian and mixed Gaussian/plane-wave hybrid orbitals. The main idea is
      to have a representation of basis sets that is flexible enough to enable
      differentiated integrals to be reinterpreted as standard integrals over modified
      basis functions. As an illustration of the method, we report a very simple
      implementation of Hartree-Fock level geometrical derivatives in finite magnetic
      fields for gauge-origin independent atomic orbitals, within the London program.
      As a quantum-chemical application, we optimize the structure of helium clusters
      and some well-known covalently bound molecules (water, ammonia and benzene)
      subject to strong magnetic fields.

PMID- 22653040
TI  - Early neonatal special care units and their scientific achievements.
AB  - Treatment of sick neonates originated in maternity and foundling hospitals in the
      19th century. Nosocomial infections and difficult logistics of wet-nursing
      prevented admission of neonates in most children's hospitals well into the 20th
      century. In this article, 31 hospitals are described, all located in large
      cities, in which preterm and sick neonates were treated before the Great
      Depression. Even though mostly initiated by private charity, these institutions
      performed research right from the start. Topics included warming and feeding
      preterm infants, collecting and distributing human milk, developing and storing
      breast milk substitutes, prevention of rickets and nosocomial infections,
      maternal and public education regarding infection control, pathoanatomic
      characterisation of diseases and malformations and epidemiologic studies of
      infant mortality. These pioneering hospitals, their founding dates, researchers
      and classic publications are presented in a table.

PMID- 22653041
TI  - Accuracy of echocardiographic assessment of pulmonary hypertension severity and
      right ventricular dysfunction in patients with chronic thromboembolic pulmonary
      hypertension.
AB  - AIM: Chronic thromboembolic pulmonary hypertension (CTEPH) results from chronic
      thrombotic occlusion of the pulmonary arterial circulation and may be potentially
      cured by pulmonary thromboendarterectomy. Echocardiography is the most practical
      modality for the assessment of right ventricular function and right heart
      pressures before and after surgery. However, there is scant data on how these
      estimates compare with the "gold standards" of invasive right heart
      catheterization and CT and MR scanning. METHODS: The records of 100 consecutive
      patients with CTEPH who subsequently underwent pulmonary thromboendarterectomy at
      our institution were studied. Right atrial (RA) and right ventricular (RV)
      systolic pressure estimated at preoperative echocardiography were compared with
      measurements at preoperative cardiac catheterization. In addition, preoperative
      echocardiographic estimates of RV systolic function by visual assessment and by
      calculation of RV index of myocardial performance were compared with preoperative
      measurements of RV ejection fraction (EF) by computed tomography (CT) or magnetic
      resonance (MR) scanning. RESULTS: Although estimates of RA and PA systolic
      pressures by echocardiography correlated significantly with those at cardiac
      catheterization (p<0.0001) in patients with CTEPH, Bland-Altman analysis
      demonstrated significant variation in these measurements compared with cardiac
      catheterization. Cohen's Kappa analysis demonstrated that agreement between echo
      and cath derived values was slight (kappa=0.1). RVEF assessed by CT or MR
      scanning correlated with echocardiographic visual assessment of RV systolic
      function (P<0.0001), and with RIMP (P=0.001), but actual measurements of right
      ventricular ejection fraction at a given assessment of right ventricular function
      by RIMP or visual assessment varied widely CONCLUSION: Caution is warranted in
      over-reliance on echo derived measurements of right heart hemodynamics and
      function in the setting of pulmonary hypertension, and where the clinical
      scenario calls the data into question, a low threshold should be maintained for
      proceeding to more advanced and invasive modalities of evaluation.

PMID- 22653043
TI  - Renalguard system in high-risk patients for contrast-induced acute kidney injury.
AB  - Contrast-induced acute kidney injury (CI-AKI) predicts unfavorable outcomes. The
      use of the RenalGuardTM(r) system, to create high urine output and fluid
      balancing, may be beneficial in preventing CI-AKI. The REMEDIAL II trial is a
      randomized, multicenter, investigator-driven trial addressing the prevention of
      CI-AKI in high risk patients. Consecutive patients with an estimated glomerular
      filtration rate (eGFR) <=30 mL/min/1.73 m2 and/or a risk score >=11 were randomly
      assigned to 1) sodium bicarbonate solution and N-acetylcysteine (NAC) (Control
      group) or 2) the RenalGuard therapy, that is, hydration with saline and NAC
      controlled by the RenalGuard System and furosemide (RenalGuard group). CI-AKI
      (defined as an increase of >=0.3 mg/dL in the serum creatinine concentration at
      48 hours after the procedure) occurred in 16/146 patients in the RenalGuard group
      (11%) and in 30/146 patients in the Control group (20.5%) (P=0.025; OR=0.47; 95%
      CI=0.24-0.92). Absolute changes in CyC at 24 hours (0.02+/-0.32 versus -0.08+/
      0.26; P=0.002) and at 48 hours (0.12+/-0.42 versus -0.03+/-0.31; P=0.001), as
      well as the rate of in-hospital dialysis (4.1% versus 0.7%; P=0.056) were higher
      in the Control group. In conclusion, the RenalGuard therapy seems to be a
      promising new approach in preventing CI-AKI in high risk patients.

PMID- 22653042
TI  - Same-day discharge after catheter ablation for routine arrhythmias: an initial
      experience.
AB  - AIM: Same-day discharge (SDD) in the setting of catheter ablation (CA) is not
      widely applied. We present our experience concerning SDD in a selected population
      of patients who underwent CA; the outcome was evaluated in terms of feasibility
      and safety. METHODS: 401 CA procedures were performed at our institution between
      January 2008 and December 2009 in 379 patients (65+/-16 years, 221 men). 336 CA
      procedures (84%) were considered eligible for SDD, after the exclusion of
      ventricular arrhythmias, atrial fibrillation, atypical atrial flutter, AV node
      ablation as well as procedures involving an arterial or transseptal access.
      Subsequently, a number of clinical and organizational exclusion criteria were
      applied. RESULTS: 223 patients were actually discharged on the same day of CA
      (56% of 401 overall CA procedures): 114 atrial flutter (AFL) and 109
      supraventricular tachycardia. Many patients were excluded before CA due to a
      limited availability of the day-hospital facility; this occurred more frequently
      in the year 2008 than 2009 (45 vs. 2, P=0.0001); in the year 2009 the rate of
      total CA procedures which underwent SDD was of 68%. Overall, three groin
      hematomas occurred, all in patients ablated for AFL. Two of them were recognized
      during the postablation CONCLUSION: SDD can be safely performed in most patients
      undergoing CA for routine arrhythmias. This may result in a significant impact on
      daily practice in terms of both organizational improvement and subjective benefit
      for the patients.

PMID- 22653044
TI  - Epicardial and pericardial adipose tissue: physiological importance and role of
      imaging techniques.
AB  - Epicardial adipose tissue (EAT) is becoming a cardiovascular risk factor.
      Multiple imaging techniques are used to measure it, each one with its prons and
      cons. We will review the literature realizing that there is still a lot of work
      that needs to be done.

PMID- 22653045
TI  - Invasive imaging of the coronary atherosclerotic plaque.
AB  - Coronary atherosclerosis has a high prevalence and is known as the leading cause
      of death worldwide. Clinically, coronary atherosclerosis is routinely evaluated
      by coronary angiography, which provides a luminogram of the coronary artery and
      allows for recognizing lumen narrowing. However, angiography does not allow for
      the direct assessment of the disease process within the coronary vessel wall.
      Today, a number of catheter-based imaging methods can overcome this shortcoming
      and provide physicians with additional information on specific morphological
      components of atherosclerotic lesions. This article discusses the abilities of
      intravascular imaging techniques such as intravascular ultrasound (IVUS), IVUS
      VH, iMAP, integrated backscatter-IVUS, intravascular optical coherence
      tomography, near-infrared spectroscopy and angioscopy, to diagnose coronary
      atherosclerosis and their potential to guide clinical decision making.

PMID- 22653046
TI  - Prognostication of cardiac CT angiography.
AB  - The rapidly emerging technique of cardiac computed tomography angiography (CTA)
      has enabled the anatomical assessment of coronary artery disease. CTA has very
      good diagnostic accuracy with the ability to detect nonobstructive from
      obstructive coronary artery disease and provides information on the presence of
      coronary artery calcification as well as on left ventricular function. Over the
      last few years, many prognostic studies have reviewed the outcome benefit of
      different scoring indices in predicting hard cardiac events. The following
      article will review the most recent literature available on the use of CTA in
      measuring luminal stenoses, identifying high-risk obstructive CAD, calcium plaque
      score, and LV function all in different models with their impact on the
      estimation of clinical risk. More recent data from a large multicenter registry
      supports the incremental benefit of CAD severity and LVEF as independent
      predictors of prognosis. Future directions and emerging applications such as the
      utility of CTA combined with perfusion analysis may lead to a new anatomical
      functional diagnostic test that may provide optimal noninvasive assessment of
      coronary artery anatomy and be superior to invasive coronary angiography.

PMID- 22653048
TI  - Exogenous inflammatory acne due to combined application of cosmetic and facial
      rubbing.
AB  - BACKGROUND: Exogenous acne refers to acneiform lesions due to external factors
      such as cosmetic agents, exposure to various oils, skin rubbing or friction or
      chloracne, now better called metabolizing acquired dioxin-induced skin hamartoma
      (MADISH). Here we report a new form of severe inflammatory exogenous acne due to
      the association of two factors: facial friction with cosmetic agents.
      OBSERVATIONS: A 15-, 17- and 19-year-old female presented at the department with
      severe inflammatory acne. In all cases, the face had been strongly rubbed in a
      compulsory manner in the previous weeks with cosmetic agents. The disease has not
      responded to various conventional acne treatments and was well controlled by a
      combination of oral corticosteroids and low-dose isotretinoin. CONCLUSION:
      Because cosmetic face friction as a cosmetic care becomes more and more
      fashionable, dermatologists should be aware of this severe clinical condition,
      which can occur in patients without a personal history of acne.

PMID- 22653050
TI  - Polyoxometalates as efficient catalysts for transformations of cellulose into
      platform chemicals.
AB  - Efficient utilisation of renewable biomass resources, particularly
      lignocellulosic biomass, for the production of chemicals and fuels has attracted
      much attention in recent years. The catalytic conversion of cellulose, the main
      component of lignocellulosic biomass, selectively into a platform chemical such
      as glucose, 5-hydroxymethyl furfural (HMF), sorbitol or gluconic acid under mild
      conditions is the most desirable route. Acid catalysis plays a crucial role in
      the conversion of cellulose via the cleavage of its glycosidic bonds. Owing to
      their unique features such as strong acidity, water-tolerance, low corrosiveness
      and recoverability, polyoxometalates have shown promising performances in
      transformations of cellulose into platform chemicals both in homogeneous and
      heterogeneous systems. This article highlights recent studies on polyoxometalates
      and polyoxometalate-based bifunctional catalysts or catalytic systems for the
      selective conversions of cellulose and cellobiose, a model molecule of cellulose,
      into platform chemicals.

PMID- 22653047
TI  - Nesprin interchain associations control nuclear size.
AB  - Nesprins-1/-2/-3/-4 are nuclear envelope proteins, which connect nuclei to the
      cytoskeleton. The largest nesprin-1/-2 isoforms (termed giant)  tether F-actin
      through their N-terminal actin binding domain (ABD). Nesprin-3, however, lacks an
      ABD and associates instead to plectin, which binds intermediate filaments.
      Nesprins are integrated into the outer nuclear membrane via their C-terminal KASH
      domain. Here, we show that nesprin-1/-2 ABDs physically and functionally interact
      with nesprin-3. Thus, both ends of nesprin-1/-2 giant are integrated at the
      nuclear surface: via the C-terminal KASH-domain and the N-terminal ABD-nesprin-3
      association. Interestingly, nesprin-2 ABD or KASH-domain overexpression leads to
      increased nuclear areas. Conversely, nesprin-2 mini (contains the ABD and KASH
      domain but lacks the massive nesprin-2 giant rod segment) expression yields
      smaller nuclei. Nuclear shrinkage is further enhanced upon nesprin-3 co
      expression or microfilament depolymerization. Our findings suggest that
      multivariate intermolecular nesprin interactions with the cytoskeleton form a
      lattice-like filamentous network covering the outer nuclear membrane, which
      determines nuclear size.

PMID- 22653051
TI  - Large spin figure of merit in a double quantum dot coupled to noncollinear
      ferromagnetic electrodes.
AB  - The spin thermoelectric effects are studied in a Rashba double quantum dot (QD)
      attached to ferromagnetic leads with noncollinear magnetic moments. The spin
      conductance G(s), spin thermopower S(s), electron thermal conductance kappa(el)
      and spin thermoelectric figure of merit Z(s)T are calculated by using Green's
      function method. We find that the magnitude of the spin figure of merit can be
      remarkably enhanced by the coexistence of the Rashba spin-orbit interaction in
      the QDs and the leads' spin polarization, and can reach even as high as 3 by
      optimizing the parameters of the structure. The angle between the leads' magnetic
      moments can act as a powerful means to manipulate the properties of the spin
      figure of merit.

PMID- 22653052
TI  - The complexities of G-protein-coupled receptor kinase function in Hedgehog
      signaling.
AB  - Hedgehog (Hh) signaling is essential for proper tissue patterning and maintenance
      and has a substantial impact on human disease. While many of the main components
      and mechanisms involved in transduction of the Hh signal have been identified,
      the details of how the pathway functions are continually being refined. One
      aspect that has attracted much attention recently is the involvement of G-protein
      coupled receptor kinases (GRKs) in the pathway. These regulators of G-protein
      coupled receptor (GPCR) signaling have an evolutionarily-conserved function in
      promoting high-threshold Hh target gene expression through regulation of
      Smoothened (Smo), a GPCR family member that activates intracellular Hh signaling.
      Several models of how GRKs impact on Smo to increase downstream signaling have
      been proposed. Recently, we demonstrated that these kinases have surprisingly
      complex and conflicting roles, acting to limit signaling through the pathway
      while also promoting Smo activity. In addition to the previously described direct
      effects of Gprk2 on Smo activation, Gprk2 also indirectly affects Hh signaling by
      controlling production of the second messenger cyclic AMP to influence Protein
      kinase A activity.

PMID- 22653053
TI  - The urogynecological side of pelvic floor MRI: the clinician's needs and the
      radiologist's role.
AB  - In pelvic floor dysfunction (PFD), magnetic resonance imaging of the pelvic floor
      supporting system from a functional point of view allows radiologists to
      recognize and classify the types of defects in each supporting structure (namely,
      the urethral supporting system, the vaginal supporting system, and the anal
      sphincter complex). Combined analysis of both the static and dynamic images of
      patients reporting stress urinary incontinence and pelvic organ prolapse has
      revealed a close relationship between certain anatomical defects in the pelvic
      organ support system and specific PFD. Because of the consistency and
      reproducibility of this relationship, radiologists can accurately identify and
      report the underlying structural defects, allowing clinicians to individually
      tailor surgical techniques for each patient. This is important because even those
      patients presenting with the same clinical symptoms may have different underlying
      structural derangement or abnormalities that may warrant a different treatment
      plan or approach. In view of the reported high rate of dysfunction recurrence
      after surgical treatment and clinicians' desire for a test that can pinpoint each
      patient's structural and anatomical defects, this approach provides the necessary
      scientific evidence on which best clinical practice can be based, and the data
      reporting system used for analysis provides a tool for accurately planning
      reconstructive surgery, reducing the risk of surgical failure, dysfunction
      recurrence, and reoperation. With the improved radiological evidence made
      possible by combined image analysis, clinicians can now have the documentation
      that they need to plan more effective procedures and thus produce better
      outcomes. This review focuses on the MRI anatomy of the pelvic floor from a
      functional point of view and from the urogynecological side of floor dysfunction
      (UI and POP), adopting a problem-oriented approach. The first section of this
      article provides the basic essential anatomical information about the pelvic
      floor and briefly reviews the pathophysiology and clinical features of SUI and
      POP. The second portion details the vital role of the radiologist in obtaining
      accurate images for the clinician to use in planning reconstructive surgery. In
      addition, it includes case examples, illustrating how to report MRI findings
      systematically and comprehensively on both the static and dynamic images, using a
      recently developed integrated MRI analytical approach from a purely functional
      point of view that may enhance radiologists' interaction with clinicians and
      bridges the gap between radiology and surgery. 

PMID- 22653054
TI  - Thymocyte responsiveness to endogenous glucocorticoids is required for
      immunological fitness.
AB  - Generation of a self-tolerant but antigen-responsive T cell repertoire occurs in
      the thymus. Although glucocorticoids are usually considered immunosuppressive,
      there is also evidence that they play a positive role in thymocyte selection. To
      address the question of how endogenous glucocorticoids might influence the
      adaptive immune response, we generated GRlck-Cre mice, in which the
      glucocorticoid receptor gene (GR) is deleted in thymocytes prior to selection.
      These mice were immunocompromised, with reduced polyclonal T cell proliferative
      responses to alloantigen, defined peptide antigens, and viral infection. This was
      not due to an intrinsic proliferation defect, because GR-deficient T cells
      responded normally when the TCR was cross-linked with antibodies or when the T
      cell repertoire was "fixed" with alphabeta TCR transgenes. Varying the affinity
      of self ligands in alphabeta TCR transgenic mice showed that affinities that
      would normally lead to thymocyte-positive selection caused negative selection,
      and alterations in the TCR repertoire of polyclonal T cells were confirmed by
      analysis of TCR Vbeta CDR3 regions. Thus, endogenous glucocorticoids are required
      for a robust adaptive immune response because of their promotion of the selection
      of T cells that have sufficient affinity for self, and the absence of thymocyte
      glucocorticoid signaling results in an immunocompromised state.

PMID- 22653055
TI  - Targeting the FOXO1/KLF6 axis regulates EGFR signaling and treatment response.
AB  - EGFR activation is both a key molecular driver of disease progression and the
      target of a broad class of molecular agents designed to treat advanced cancer.
      Nevertheless, resistance develops through several mechanisms, including
      activation of AKT signaling. Though much is known about the specific molecular
      lesions conferring resistance to anti-EGFR-based therapies, additional molecular
      characterization of the downstream mediators of EGFR signaling may lead to the
      development of new classes of targeted molecular therapies to treat resistant
      disease. We identified a transcriptional network involving the tumor suppressors
      Kruppel-like factor 6 (KLF6) and forkhead box O1 (FOXO1) that negatively
      regulates activated EGFR signaling in both cell culture and in vivo models.
      Furthermore, the use of the FDA-approved drug trifluoperazine hydrochloride
      (TFP), which has been shown to inhibit FOXO1 nuclear export, restored sensitivity
      to AKT-driven erlotinib resistance through modulation of the KLF6/FOXO1 signaling
      cascade in both cell culture and xenograft models of lung adenocarcinoma.
      Combined, these findings define a novel transcriptional network regulating
      oncogenic EGFR signaling and identify a class of FDA-approved drugs as capable of
      restoring chemosensitivity to anti-EGFR-based therapy for the treatment of
      metastatic lung adenocarcinoma.

PMID- 22653056
TI  - Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS
      inflammatory disease.
AB  - In inflammatory CNS conditions such as multiple sclerosis (MS), current options
      to treat clinical relapse are limited, and more selective agents are needed.
      Disruption of the blood-brain barrier (BBB) is an early feature of lesion
      formation that correlates with clinical exacerbation, leading to edema,
      excitotoxicity, and entry of serum proteins and inflammatory cells. Here, we
      identify astrocytic expression of VEGF-A as a key driver of BBB permeability in
      mice. Inactivation of astrocytic Vegfa expression reduced BBB breakdown,
      decreased lymphocyte infiltration and neuropathology in inflammatory and
      demyelinating lesions, and reduced paralysis in a mouse model of MS. Knockdown
      studies in CNS endothelium indicated activation of the downstream effector eNOS
      as the principal mechanism underlying the effects of VEGF-A on the BBB. Systemic
      administration of the selective eNOS inhibitor cavtratin in mice abrogated VEGF-A
      induced BBB disruption and pathology and protected against neurologic deficit in
      the MS model system. Collectively, these data identify blockade of VEGF-A
      signaling as a protective strategy to treat inflammatory CNS disease.

PMID- 22653057
TI  - Fatal breathing dysfunction in a mouse model of Leigh syndrome.
AB  - Leigh syndrome (LS) is a subacute necrotizing encephalomyelopathy with gliosis in
      several brain regions that usually results in infantile death. Loss of murine
      Ndufs4, which encodes NADH dehydrogenase (ubiquinone) iron-sulfur protein 4,
      results in compromised activity of mitochondrial complex I as well as progressive
      neurodegenerative and behavioral changes that resemble LS. Here, we report the
      development of breathing abnormalities in a murine model of LS. Magnetic
      resonance imaging revealed hyperintense bilateral lesions in the dorsal brain
      stem vestibular nucleus (VN) and cerebellum of severely affected mice. The mutant
      mice manifested a progressive increase in apnea and had aberrant responses to
      hypoxia. Electrophysiological recordings within the ventral brain stem pre
      Botzinger respiratory complex were also abnormal. Selective inactivation of
      Ndufs4 in the VN, one of the principle sites of gliosis, also led to breathing
      abnormalities and premature death. Conversely, Ndufs4 restoration in the VN
      corrected breathing deficits and prolonged the life span of knockout mice. These
      data demonstrate that mitochondrial dysfunction within the VN results in aberrant
      regulation of respiration and contributes to the lethality of Ndufs4-knockout
      mice.

PMID- 22653058
TI  - FOXO1 in the ventromedial hypothalamus regulates energy balance.
AB  - The transcription factor FOXO1 plays a central role in metabolic homeostasis by
      regulating leptin and insulin activity in many cell types, including neurons.
      However, the neurons mediating these effects and the identity of the molecular
      targets through which FOXO1 regulates metabolism remain to be defined. Here, we
      show that the ventral medial nucleus of the hypothalamus (VMH) is a key site of
      FOXO1 action. We found that mice lacking FOXO1 in steroidogenic factor 1 (SF-1)
      neurons of the VMH are lean due to increased energy expenditure. The mice also
      failed to appropriately suppress energy expenditure in response to fasting.
      Furthermore, these mice displayed improved glucose tolerance due to increased
      insulin sensitivity in skeletal muscle and heart. Gene expression profiling and
      sequence analysis revealed several pathways regulated by FOXO1. In addition, we
      identified the nuclear receptor SF-1 as a direct FOXO1 transcriptional target in
      the VMH. Collectively, our data suggest that the transcriptional networks
      modulated by FOXO1 in VMH neurons are key components in the regulation of energy
      balance and glucose homeostasis.

PMID- 22653059
TI  - G protein-coupled receptor 21 deletion improves insulin sensitivity in diet
      induced obese mice.
AB  - Obesity-induced inflammation is a key component of systemic insulin resistance,
      which is a hallmark of type 2 diabetes. A major driver of this
      inflammation/insulin resistance syndrome is the accumulation of proinflammatory
      macrophages in adipose tissue and liver. We found that the orphan GPCR Gpr21 was
      highly expressed in the hypothalamus and macrophages of mice and that whole-body
      KO of this receptor led to a robust improvement in glucose tolerance and systemic
      insulin sensitivity and a modest lean phenotype. The improvement in insulin
      sensitivity in the high-fat diet-fed (HFD-fed) Gpr21 KO mouse was traced to a
      marked reduction in tissue inflammation caused by decreased chemotaxis of Gpr21
      KO macrophages into adipose tissue and liver. Furthermore, mice lacking
      macrophage expression of Gpr21 were protected from HFD-induced inflammation and
      displayed improved insulin sensitivity. Results of in vitro chemotaxis studies in
      human monocytes suggested that the defect in chemotaxis observed ex vivo and in
      vivo in mice is also translatable to humans. Cumulatively, our data indicate that
      GPR21 has a critical function in coordinating macrophage proinflammatory activity
      in the context of obesity-induced insulin resistance.

PMID- 22653062
TI  - Acrylates.

PMID- 22653063
TI  - Acrylates in contact dermatitis.
AB  - Acrylates are plastic materials that are formed by the polymerization of monomers
      derived from acrylic or methacrylic acid. They have found numerous applications
      in paints, varnishes and adhesives, in the printing industry, in the medical and
      dental professions, and in artificial nails. Beginning in the 1950s, many reports
      of occupational and nonoccupational allergic contact dermatitis to (meth)acrylate
      monomers have been published. These molecules are strong irritants, and patch
      testing can induce active sensitization. When patch tested, acrylate-allergic
      patients often display multiple positive tests. These reactions may represent
      cross-reactions, or concomitant reactions due to the presence, in the products
      responsible for sensitization, of impurities not disclosed in material safety
      data sheets. (Meth)acrylates are volatile and unstable chemicals, as demonstrated
      by their rapid disappearance from commercially available patch test allergens
      when exposed to air for more than a few hours.

PMID- 22653060
TI  - Ribosomal RACK1 promotes chemoresistance and growth in human hepatocellular
      carcinoma.
AB  - Coordinated translation initiation is coupled with cell cycle progression and
      cell growth, whereas excessive ribosome biogenesis and translation initiation
      often lead to tumor transformation and survival. Hepatocellular carcinoma (HCC)
      is among the most common and aggressive cancers worldwide and generally displays
      inherently high resistance to chemotherapeutic drugs. We found that RACK1, the
      receptor for activated C-kinase 1, was highly expressed in normal liver and
      frequently upregulated in HCC. Aberrant expression of RACK1 contributed to in
      vitro chemoresistance as well as in vivo tumor growth of HCC. These effects
      depended on ribosome localization of RACK1. Ribosomal RACK1 coupled with
      PKCbetaII to promote the phosphorylation of eukaryotic initiation factor 4E
      (eIF4E), which led to preferential translation of the potent factors involved in
      growth and survival. Inhibition of PKCbetaII or depletion of eIF4E abolished
      RACK1-mediated chemotherapy resistance of HCC in vitro. Our results imply that
      RACK1 may function as an internal factor involved in the growth and survival of
      HCC and suggest that targeting RACK1 may be an efficacious strategy for HCC
      treatment.

PMID- 22653064
TI  - Recommendations for a screening series for allergic contact eyelid dermatitis.
AB  - BACKGROUND: Although allergic contact dermatitis of the eyelids is a common
      condition, limited information is available regarding the selection of patch
      testing chemicals for proper evaluation. OBJECTIVE: The purpose of this analysis
      was to evaluate the relevance of allergens responsible for allergic eyelid
      dermatitis among a series of patch-tested patients attending our clinic at the
      University of Miami and compare these results to published studies in the
      literature. METHODS: Data were retrospectively reviewed for eyelid-only
      dermatitis from clinically relevant patch-test evaluations performed between
      December 2004 and January 2007. RESULTS: Formaldehyde was the most frequently
      encountered antigen, accounting for 45.83% (11/24) of the cases, followed by
      nickel 33.33% (8/24) and balsam of Peru (Myroxylon pereirae) 29.17% (7/24). In
      addition, not only did we find a higher prevalence of certain allergens when
      compared with other studies, but we identified several relevant allergens not
      previously reported at other referral centers. CONCLUSIONS: The allergens found
      to be relevant in eyelid dermatitis vary among different regions. These data may
      help contribute to generating a standard screening tool to improve the detection
      and management of these cases.

PMID- 22653065
TI  - Fragrance series testing in eyelid dermatitis.
AB  - BACKGROUND: Allergic contact dermatitis is considered one of the most common
      causes of eyelid dermatitis. In addition to metals and topical antibiotics,
      fragrances have emerged as a leading source of contact allergy for individuals
      with this condition. OBJECTIVES: The objective of this study was to determine the
      added benefit of including a fragrance tray when patch testing patients
      presenting with eyelid dermatitis. METHODS: During a 4.5-year period, all
      patients with suspected allergic contact dermatitis involving the eyelids were
      patch tested with both standard and fragrance trays. RESULTS: One hundred
      consecutive patients with eyelid dermatitis were patch tested. Of these patients,
      42 (42%) tested positive for 1 or more allergens within the fragrance series. Of
      these patients, 15 (36%) had no fragrance markers detected on the standard
      series, and these allergens would therefore have been missed had fragrance series
      testing not been performed. Overall, fragrance markers within the standard series
      detected 73.2% (41/56) of cases of fragrance allergy. CONCLUSIONS: Our results
      suggest that there may be a significant benefit to fragrance series testing in
      patients with eyelid dermatitis. Fragrance tray inclusion in this population may
      identify additional cases of fragrance allergy that are missed by the standard
      series.

PMID- 22653067
TI  - Does the new standard for eugenol designed to protect against contact
      sensitization protect those sensitized from elicitation of the reaction?
AB  - BACKGROUND: Potential fragrance allergens used in daily products should have a
      concentration limited to levels that are at, or below, acceptable exposure levels
      based on the quantitative risk assessment for the induction of dermal
      sensitization. To date, there are insufficient data to discern any quantitative
      relationship between induction and elicitation concentrations for fragrance
      ingredients that have a potential for dermal sensitization. When available, these
      data should be used to confirm the effectiveness of quantitative risk assessment
      based risk management procedures. OBJECTIVE: In this study, the relationship
      between the allergen concentration and the time to elicit allergic contact
      dermatitis in eugenol-sensitized patients was studied. The products used to
      elicit allergic contact dermatitis had a concentration of eugenol that was equal
      to, or below, the International Fragrance Association standard. METHODS:
      Volunteers with and without known sensitization to eugenol were patch tested with
      various concentrations of eugenol (dilution series) and also underwent repeated
      open application tests (ROATs). This study model has previously been successfully
      used with stronger sensitizers. RESULTS: In this study, allergic contact
      dermatitis, as evidenced by a positive ROAT, could not be elicited by any of the
      concentrations studied, including in those patients where the patch tests were
      positive. CONCLUSIONS: When tested in a 3-week ROAT at, or below, its current
      International Fragrance Association Standard, eugenol did not induce reactions
      even in those known to be sensitized. Whether this represents a false-negative
      result for a weak allergen is unknown.

PMID- 22653068
TI  - Is quaternium-15 a formaldehyde releaser? Correlation between positive patch test
      reactions to formaldehyde and quaternium-15.
AB  - BACKGROUND: The question of whether quaternium-15 is a formaldehyde releaser is
      controversial. Understanding this relationship is critical because of the
      widespread use of quaternium-15 and the need to properly advise formaldehyde
      allergic individuals. OBJECTIVES: This study aimed to look for an association
      between allergy to quaternium-15 and formaldehyde by correlating reactions to
      both and to correlate the intensity of positive patch test results to
      formaldehyde with reactivity to quaternium-15. METHODS: This is a retrospective
      analysis of 1905 patients who underwent patch testing for allergic contact
      dermatitis. Associations were analyzed by chi testing. RESULTS: Of all patients,
      9.5% reacted to quaternium-15, 7.2% reacted to formaldehyde, and 5.4% reacted to
      both (P < 0.001). Of 137, 86 had strong (2 or 3+) and 51 had weak (1+ or +/-)
      formaldehyde reactions; there was no relationship between the severity of
      formaldehyde reactivity and responsiveness to quaternium-15 (P = 0.229). Sex
      analysis did not change these findings. LIMITATIONS: This study is limited by its
      retrospective analysis and small sample size. CONCLUSIONS: A statistically
      significant relationship exists between reactivity to quaternium-15 and
      formaldehyde; however, the severity of the formaldehyde reaction does not predict
      reactivity to quaternium-15. Despite coreactivity with formaldehyde, quaternium
      15 may not be a significant formaldehyde releaser. The coreactivity between
      quaternium-15 and formaldehyde requires further studies.

PMID- 22653066
TI  - Fire-retardant clothing-related dermatitis.
AB  - BACKGROUND: Several laborers in a refinery unit undergoing a work over noted skin
      eruptions. Signs and symptoms included erythema, pruritus, scaling, and
      perifollicular inflammation on skin contacted by fire-retardant clothing (FRC).
      OBJECTIVE: The purposes of this report were to show a correlation between this
      rash outbreak and the use of FRC, to report the investigative results as to what
      aspect of the FRC most likely caused the dermatitis, and to present how this
      outbreak was ended. METHODS: Employees received questionnaires, were examined,
      and received patch testing, and pH testing of FRC was performed to evaluate the
      causative factors. RESULTS: More than 100 workers reported a rash, and
      approximately a third of these individuals exhibited a unique rash. There was a
      trend toward Hispanic and white workers being more affected than black workers.
      The onset of the rash peaked from June to August. This FRC-related rash resolved
      with the use of manufacturer-recommended laundering procedures. CONCLUSIONS: The
      FRC-associated eruption was most likely a form of irritant contact dermatitis due
      to inadequate laundering procedures. The most effective preventative measure
      other than proper laundering was the use of underclothing to prevent contact of
      FRC with sweat-moistened skin.

PMID- 22653070
TI  - Tea tree oil.
AB  - Tea tree oil is an increasingly popular ingredient in a variety of household and
      cosmetic products, including shampoos, massage oils, skin and nail creams, and
      laundry detergents. Known for its potential antiseptic properties, it has been
      shown to be active against a variety of bacteria, fungi, viruses, and mites. The
      oil is extracted from the leaves of the tea tree via steam distillation. This
      essential oil possesses a sharp camphoraceous odor followed by a menthol-like
      cooling sensation. Most commonly an ingredient in topical products, it is used at
      a concentration of 5% to 10%. Even at this concentration, it has been reported to
      induce contact sensitization and allergic contact dermatitis reactions. In 1999,
      tea tree oil was added to the North American Contact Dermatitis Group screening
      panel. The latest prevalence rates suggest that 1.4% of patients referred for
      patch testing had a positive reaction to tea tree oil.

PMID- 22653069
TI  - Erythema papulosa semicircularis recidivans:  a new reactive dermatitis?
AB  - BACKGROUND: Nine patients with recrudescent and centrifugally expanded
      papuloerythematous eruptions were observed in our outpatient department during
      the recent 8 years. The patients were all young and middle-aged men presenting
      with characteristic skin lesions and relapsing each year in the warm humid
      season. Such an observation has not yet been described in the English literature.
      OBJECTIVES: The objective of this study was to describe the clinical
      characteristics and explore the possible etiologies of our cases. In addition,
      differential diagnosis with other common figurate erythemas was also reviewed and
      discussed. METHODS: In 5 of the patients, skin-prick testing was performed with
      common airborne and food allergens, and skin patch testing with the Chinese
      baseline series of contact allergens was performed, along with histopathologic
      examinations. RESULTS: The skin findings in our patients were conspicuous in
      their papular characteristics of the borders, semicircular arrangement, male
      predominance, and yearly crescendo of recurrence in warm seasons. Histopathologic
      examination showed superficial perivascular dermatitis, whereas skin-prick
      testing and patch testing showed negative results. CONCLUSIONS: Although the
      etiology of our cases remains unclear at present, the clinical characteristics
      make them distinct from other well-described figurate erythemas characterized by
      annular erythematous lesions. We propose the term erythema papulosa
      semicircularis recidivans to depict a special form of recurrent
      papuloerythematous figurate erythema of unknown etiology.

PMID- 22653071
TI  - Dog tag dermatitis and nickel allergy in the military.

PMID- 22653073
TI  - Atopic dermatitis in adults.

PMID- 22653072
TI  - Fixed drug eruption due to quinine in tonic water: study of cross-reactions.

PMID- 22653075
TI  - Connubial allergic contact dermatitis caused by fragrance ingredients.

PMID- 22653076
TI  - Use of a surgical specimen-collection kit to improve mediastinal lymph-node
      examination of resectable lung cancer.
AB  - INTRODUCTION: Pathologic examination of mediastinal lymph nodes (MLNs) after
      resection of non-small-cell lung cancer is critical in the determination of
      prognosis and postoperative management. Although systematic nodal dissection is
      recommended, the quality of pathologic lymph-node staging often falls short of
      recommendations in practice. We tested the feasibility of improving pathologic
      lymph-node staging of resectable non-small-cell lung cancer by using a prelabeled
      specimen-collection kit. METHODS: Case-control study with comparison of 51
      resections, using a special lymph-node collection kit, with 51 controls matched
      for surgeon, extent of resection, pathologist, and T category. Appropriate
      statistical methods were used for all comparisons. RESULTS: The median number of
      MLNs examined increased from one in the control group, to six in the case group
      (p < 0.001). The percentage of resections attaining the National Comprehensive
      Cancer Network-recommended quality of MLN examination, and the proportion that
      would have been eligible for recent landmark postresection adjuvant therapy
      trials increased significantly (p < 0.001). The duration of surgery and
      postoperative complication rates were similar between cases and controls.
      Eighteen percent of kit cases had positive MLN, compared with 8% of controls.
      CONCLUSIONS: The use of a specialized specimen-collection kit for MLN examination
      was feasible, markedly improved MLN staging, and showed a trend toward increased
      detection of patients with MLN metastasis, with only a modest increase in
      duration of surgery, and no increase in perioperative morbidity, mortality, or
      hospital length of stay.

PMID- 22653077
TI  - Adopting integrated care pathways in non-small-cell lung cancer: from theory to
      practice.
AB  - INTRODUCTION: Integrated care pathways (ICPs) have been proposed as effective
      strategies for quality improvement. To date, limited data are available that
      detail the methodology to design an optimal care pathway for patients with non
      small-cell lung cancer (NSCLC). The main aim of this study was to assess the
      quality of health care delivered to lung cancer patients referred to a hub
      university hospital. METHODS: All professionals involved with the management of
      NSCLC patients, in cooperation with health care researchers, identified 11
      quality indicators and associated benchmarks. These were used to estimate the
      quality and efficiency of health care delivered to a cohort of 175 NSCLC
      patients. RESULTS: The gap between "desired" and "actual" performance has been
      measured by benchmarking current practice against key quality indicators.
      Diagnostic workup, multidisciplinary team care and medical treatment of advanced
      disease have emerged as areas of good performance. Conversely, the management of
      early-stage disease offers room for improvement, in terms of both accuracy of
      nodal staging and surgical timeliness. CONCLUSIONS: Analyzing the process of
      caring for NSCLC patients is feasible and offers room for improvement. Acquired
      knowledge may be shared with hospital administrators, guide the revision of ICPs,
      and enable the delivery of consistent, high-quality clinical standards.

PMID- 22653078
TI  - Insightful practice: a reliable measure for medical revalidation.
AB  - BACKGROUND: Medical revalidation decisions need to be reliable if they are to
      reassure on the quality and safety of professional practice. This study tested an
      innovative method in which general practitioners (GPs) were assessed on their
      reflection and response to a set of externally specified feedback. SETTING AND
      PARTICIPANTS: 60 GPs and 12 GP appraisers in the Tayside region of Scotland, UK.
      METHODS: A feedback dataset was specified as (1) GP-specific data collected by
      GPs themselves (patient and colleague opinion; open book self-evaluated knowledge
      test; complaints) and (2) Externally collected practice-level data provided to
      GPs (clinical quality and prescribing safety). GPs' perceptions of whether the
      feedback covered UK General Medical Council specified attributes of a 'good
      doctor' were examined using a mapping exercise. GPs' professionalism was examined
      in terms of appraiser assessment of GPs' level of insightful practice, defined
      as: engagement with, insight into and appropriate action on feedback data. The
      reliability of assessment of insightful practice and subsequent recommendations
      on GPs' revalidation by face-to-face and anonymous assessors were investigated
      using Generalisability G-theory. MAIN OUTCOME MEASURES: Coverage of General
      Medical Council attributes by specified feedback and reliability of assessor
      recommendations on doctors' suitability for revalidation. RESULTS: Face-to-face
      assessment proved unreliable. Anonymous global assessment by three appraisers of
      insightful practice was highly reliable (G=0.85), as were revalidation decisions
      using four anonymous assessors (G=0.83). CONCLUSIONS: Unlike face-to-face
      appraisal, anonymous assessment of insightful practice offers a valid and
      reliable method to decide GP revalidation. Further validity studies are needed.

PMID- 22653079
TI  - Bibliography. Mineral metabolism. Current world literature.

PMID- 22653082
TI  - Ordered mesoporous metal oxides: synthesis and applications.
AB  - Great progress has been made in the preparation and application of ordered
      mesoporous metal oxides during the past decade. However, the applications of
      these novel and interesting materials have not been reviewed comprehensively in
      the literature. In the current review we first describe different methods for the
      preparation of ordered mesoporous metal oxides; we then review their applications
      in energy conversion and storage, catalysis, sensing, adsorption and separation.
      The correlations between the textural properties of ordered mesoporous metal
      oxides and their specific performance are highlighted in different examples,
      including the rate of Li intercalation, sensing, and the magnetic properties.
      These results demonstrate that the mesoporosity has a direct impact on the
      properties and potential applications of such materials. Although the scope of
      the current review is limited to ordered mesoporous metal oxides, we believe that
      the information may be useful for those working in a number of fields.

PMID- 22653081
TI  - Effect of viscosity on food transport and swallow initiation during eating of two
      phase food in normal young adults: a pilot study.
AB  - When eating food containing both liquid and solid phases (two-phase food), the
      liquid component frequently enters the hypopharynx before swallowing, which may
      increase the risk of aspiration. We therefore tested whether preswallow bolus
      transport and swallow initiation would change as the viscosity of two-phase food
      was increased. Fiberoptic endoscopy was recorded while 18 adult subjects ate 5 g
      of steamed rice with 3 ml of blue-dye water. Liquid viscosity was set at four
      levels by adding a thickening agent (0, 1, 2, and 4 wt%, respectively). We
      measured the timing of the leading edge of the food reaching the base of the
      epiglottis, as well as the location of the leading edge at swallow initiation. As
      viscosity increased, the leading edge of the food reached the epiglottis
      significantly later during chewing and was higher in the pharynx at swallow
      onset. The time after the leading edge reached the epiglottis did not vary among
      the viscosities of the two-phase food. This study found that the initial
      viscosity of two-phase food significantly altered oropharyngeal bolus flow and
      the timing of swallow initiation. Accordingly, increased two-phase food viscosity
      may delay food entry into the pharynx and be of use in dysphagic diets.

PMID- 22653083
TI  - Low-temperature ozone exposure technique to modulate the stoichiometry of WOx
      nanorods and optimize the electrochromic performance.
AB  - A low-temperature ozone exposure technique was employed for the post-treatment of
      WO(x) nanorod thin films fabricated from hot-wire chemical vapor deposition
      (HWCVD) and ultrasonic spray deposition (USD) techniques. The resulting films
      were characterized with x-ray diffraction (XRD), transmission electron microscopy
      (TEM), Raman spectroscopy, UV-vis-NIR spectroscopy and x-ray photoelectron
      spectroscopy (XPS). The stoichiometry and surface crystallinity of the WO(x) thin
      films were subsequently modulated upon ozone exposure and thermal annealing
      without particle growth. The electrochromic performance was studied in a LiClO(4)
      propylene carbonate electrolyte, and the results suggest that the low-temperature
      ozone exposure technique is superior to the traditional high-temperature thermal
      annealing (employed to more fully oxidize the WO(x)). The optical modulation at
      670 nm was improved from 35% for the as-deposited film to 57% for the film after
      ozone exposure at 150  degrees C. The coloration efficiency was improved and the
      switching speed to the darkened state was significantly accelerated from 18.0 s
      for the as-deposited film to 11.8 s for the film after the ozone exposure. The
      process opens an avenue for low-temperature and cost-effective manufacturing of
      electrochromic films, especially on flexible polymer substrates.

PMID- 22653085
TI  - Cardiovascular and metabolic regulation by the adiponectin/C1q/tumor necrosis
      factor-related protein family of proteins.

PMID- 22653084
TI  - C1q/tumor necrosis factor-related protein-3, a newly identified adipokine, is a
      novel antiapoptotic, proangiogenic, and cardioprotective molecule in the ischemic
      mouse heart.
AB  - BACKGROUND: Obesity and diabetes mellitus adversely affect postischemic heart
      remodeling via incompletely understood mechanisms. C1q/tumor necrosis factor
      related protein-3 (CTRP3) is a newly identified adipokine exerting beneficial
      metabolic regulation, similar to adiponectin. The aim of the present study was to
      determine whether CTRP3 may regulate postischemic cardiac remodeling and cardiac
      dysfunction, and, if so, to elucidate the underlying mechanisms. METHODS AND
      RESULTS: Male adult mice were subjected to myocardial infarction (MI) via left
      anterior descending coronary artery occlusion. Both the effect of MI on
      endogenous CTRP3 expression/production and the effect of exogenous CTRP3
      (adenovirus or recombinant CTRP3) replenishment on MI injury were investigated.
      MI significantly inhibited adipocyte CTRP3 expression and reduced the plasma
      CTRP3 level, reaching a nadir 3 days after MI. CTRP3 replenishment improved
      survival rate (P<0.05), restored cardiac function, attenuated cardiomyocyte
      apoptosis, increased revascularization, and dramatically reduced interstitial
      fibrosis (all P<0.01). CTRP3 replenishment had no significant effect on cardiac
      AMP-activated protein kinase phosphorylation but significantly increased Akt
      phosphorylation and expression of hypoxia inducing factor-1alpha and vascular
      endothelial growth factor. Surprisingly, treatment of human umbilical vascular
      endothelial cells with CTRP3 did not directly affect nitric oxide production or
      tube formation. However, preconditioned medium from CTRP3-treated cardiomyocytes
      significantly enhanced human umbilical vascular endothelial cell tube formation,
      an effect blocked by either pretreatment of cardiomyocytes with a PI3K inhibitor
      or pretreatment of human umbilical vascular endothelial cells with a vascular
      endothelial growth factor inhibitor. Finally, the protective effect of adipocyte
      conditioned medium against hypoxia-induced cardiomyocyte injury is significantly
      blunted when CTRP3 is knocked down. CONCLUSION: CTRP3 is a novel antiapoptotic,
      proangiogenic, and cardioprotective adipokine, the expression of which is
      significantly inhibited after MI.

PMID- 22653086
TI  - Cognitive impairment and formal thought disorders in parents of early-onset
      schizophrenia patients.
AB  - BACKGROUND: Both cognitive impairment and formal thought disorder (communication
      disturbances) found in patients with schizophrenia are also commonly observed in
      their relatives. Recently, the role of such deficits as putative endophenotypes
      of schizophrenia has been proposed. However, in a majority of studies, the
      families of adult patients were assessed whereas the relatives of early-onset
      psychotic subjects were rarely studied. The aim of our study was to evaluate the
      presence of cognitive impairment and formal thought disorders in parents of
      adolescents with a diagnosis of schizophrenia spectrum disorder (SSD) and in
      matched healthy controls. METHOD: Thirty-eight parents of 29 SSD adolescents and
      38 healthy controls were assessed with a battery of neurocognitive tests and the
      Thought, Language and Communication Scale. RESULTS: Parents of schizophrenia
      patients showed an increased tendency for perseverative thinking when compared to
      matched healthy controls. No statistically significant differences in cognitive
      functioning were observed between the groups. CONCLUSION: These results may
      suggest the need for further exploration of communication disturbances as a
      potential endophenotypic marker of early-onset schizophrenia.

PMID- 22653087
TI  - Effect of portal haemodynamics on liver graft and intestinal mucosa after small
      for-size liver transplantation in swine.
AB  - BACKGROUND: After small-for-size graft (SFSG) transplantation, elevated portal
      venous pressure (PVP) may lead to postoperative liver damage. Herein we evaluated
      the impact of portocaval shunt (PCS) to control PVP on liver grafts and intestine
      following SFSG transplantation. METHODS: Nineteen SFSG transplantations were
      performed with 30% of native liver in swine. Swine were divided into 3 groups: a
      high-flow shunt group (HS: n = 7), in which portal venous flow (PVF) was reduced
      with a 10-mm diameter PCS; a low-flow shunt group (LS: n = 6), in which PVF was
      reduced with a 5-mm diameter PCS, and a no-shunt group (NS: n = 6), in which no
      PCS was placed. RESULTS: Seven-day survivals were 83.3% in NS, 100% in LS and 0%
      in HS (p = 0.0088). PVP was significantly higher in the NS group (p = 0.0001;
      mean +/- SEM NS/LS/HS: 20.5 +/- 0.7/14.0 +/- 1.2/11.6 +/- 0.5 mm Hg). The LS
      group exhibited the highest compliance (PVF/PVP; NS/LS/HS 42.7 +/- 10.9/44.6 +/-
      4.9/37.7 +/- 8.3 ml/min/mm Hg; p = 0.009), the lowest aspartate aminotransferase
      (NS/LS/HS 562 +/- 18/370 +/- 55/720 +/- 130 IU/l; p = 0.0493), and suppressed
      deleterious alternations of the hepatic parenchyma and intestinal mucosa.
      CONCLUSIONS: Portal hypertension after SFSG transplantation impaired liver and
      intestinal mucosa; however, inadequate portal flow impaired not only the liver,
      but also survival.

PMID- 22653088
TI  - The meanings associated with medicines in heart failure patients.
AB  - BACKGROUND: The purpose of this study was to explore the theoretical linkages
      between symptom experiences and meaning associated with medication adherence. The
      specific objectives were to evaluate the key constructs of Meaning-Response
      theory for understanding medication adherence in patients with chronic heart
      failure; to assess the influence of symptom persistence on the meaning associated
      with prescribed medicines; and to explore the extent to which meaningful
      associations improve medication adherence. Among patients with heart failure,
      poor medication adherence occurs in over half of the population, resulting in
      high rates of symptom exacerbation, avoidable hospitalization, and death. Nurses
      play a key role in facilitating self-management skills, but patients' perceptions
      of the relationship between symptoms and medicines is not clear. METHODS: Using a
      prospective mixed methods design, the study assessed patients' (n=10) perception
      of chronic heart failure symptoms and medication adherence. Patients completed
      guided interviews related to six concepts of meaning ascribed to medication use
      and four standardized measures of medication-related beliefs, behaviours,
      symptoms, and satisfaction. RESULTS: This study suggests that patients'
      perception of meaning associated with medication taking was categorized as
      positive, negative, or absent. Symptom persistence influenced a majority of
      patient beliefs in the efficacy medicines, and patients with more positive
      meaningful associations with their medicines were more likely to remain adherent
      during the course of this study. CONCLUSIONS: Development of meaningful
      associations with medicines may improve long-term adherence with prescribed
      medication in heart failure.

PMID- 22653089
TI  - Knowledge, attitudes, and beliefs about acute coronary syndrome in patients
      diagnosed with ACS: an Irish cross-sectional study.
AB  - BACKGROUND: To reduce mortality and morbidity associated with acute coronary
      syndrome (ACS), individuals who experience ACS symptoms should seek treatment
      promptly. However, for this to be possible, they must adopt appropriate attitudes
      and beliefs about ACS symptoms and have the prerequisite knowledge to respond to
      those symptoms. AIM: This paper details the results of a cross-sectional Irish
      study that measured knowledge, attitudes, and beliefs about ACS in patients
      diagnosed with ACS. METHODS: A total of 1947 patients were enrolled in the study.
      Recruitment took place across five academic teaching hospitals in Dublin,
      Ireland. Knowledge, attitudes, and beliefs about ACS were measured using the ACS
      Response Index questionnaire. RESULTS: Almost half the patients (n=49.5%)
      demonstrated high knowledge levels (i.e. >70% of correct answers) about ACS
      symptoms. The majority recognized chest pain/pressure (98.9%) and left arm pain
      (90.2%) as symptoms. Many failed to associate jaw pain, heartburn and/or
      indigestion (44.7%), nausea and vomiting (47.6%), and neck pain (42.5%) with a
      heart attack. Higher knowledge levels were independently associated with higher
      levels of education (p=0.007), a history of angina (p=0.001), and attitudes
      (p=<0.001) and beliefs (p=<0.001) that are consistent with positively decisive
      responses to ACS symptoms. CONCLUSION: Despite having experienced an ACS event,
      overall knowledge levels were poor. Higher knowledge levels were associated with
      better attitudes and beliefs, indicating the inextricable relationship between
      all three components. Educational programmes should incorporate all three
      components so that prompt behaviour can be initiated when symptoms arise.

PMID- 22653090
TI  - High nutritional risk is associated with worse health-related quality of life in
      patients with heart failure beyond sodium intake.
AB  - BACKGROUND: The most desirable outcome in heart failure (HF) management is to
      improve health-related quality of life (HRQoL) as a patient-centred health
      outcome. Nutrition is assumed to be important in HF management, whereas there is
      little evidence that nutritional risk affects HRQoL, except for sodium. PURPOSE:
      We aimed to determine whether nutritional risk is associated with worse HRQoL
      after controlling for daily sodium intake. METHODS: A total of 134 consecutive
      patients with HF [age 63 +/- 11 years, 35% female, 45% New York Heart Association
      (NYHA) class III/IV, ejection fraction (EF) 33 +/- 13%] completed the Nutrition
      Screening Initiative (NSI) to assess nutritional risk and a 24-h urine sodium
      excretion assessment to estimate daily sodium intake at baseline. The Minnesota
      Living with HF Questionnaire was used to evaluate HRQoL at baseline and 6 months
      later. Hierarchical linear regressions were used to determine whether nutritional
      risk predicted HRQoL at baseline and 6 months later. RESULTS: Seventy-eight
      (58.2%) patients had high nutritional risk as indicated by a total NSI score >=
      6. Increased nutritional risk was independently associated with worse HRQoL at
      baseline and 6 months later (beta = 0.33, p < 0.001; beta = 0.35, p < 0.001,
      respectively), after controlling for age, gender, aetiology, body mass index,
      NYHA class, EF, total comorbidity score, prescribed medications, and daily sodium
      intake. CONCLUSION: These findings show that higher nutritional risk beyond
      sodium intake affects worse HRQoL in patients with HF. Further work is required
      to provide specific dietary guidelines to improve health outcomes for patients
      with HF.

PMID- 22653091
TI  - Variegated dermoscopy of in situ melanoma.
AB  - BACKGROUND: Melanomas in situ (MIS) are difficult to diagnose, lacking well
      established dermoscopic descriptors. OBJECTIVE: The aim of this study was to
      improve the identification of early melanomas describing the variegated
      dermoscopic features of MIS and their correlation with demographic and clinical
      aspects. METHODS: Dermoscopic images of 114 histologically proven MIS were
      evaluated by 3 expert dermoscopists and classified into their main dermoscopic
      patterns. Dermoscopic features were also considered for their correlation with
      clinical parameters. RESULTS: Eight different dermoscopic subtypes of MIS were
      identified: reticular grey-blue (27.2%), reticular (21.1%), multicomponent
      (20.2%), island (10.5%), spitzoid (7%), inverse network (6.1%), 'net-blue
      globules' (5.3%) and globular (2.6%). Clinical characteristics of lesions and
      patients varied according to the different dermoscopic groups. CONCLUSION: We
      hypothesize that the different dermoscopic subgroups of MIS correspond to lesions
      with a different origin and, possibly, various patterns of growth and a different
      biological behaviour.

PMID- 22653093
TI  - [Student evaluation of anesthesiological teaching: steering instrument of a
      continuous improvement process].
AB  - BACKGROUND: The amendment to the higher education act ("Hochschulrahmengesetz")
      of 1998 postulates an evaluation of teaching for quality assurance. Hence, in the
      winter semester of 2004 the University Medical Center of Bonn introduced a
      semester questionnaire for students to evaluate the quality of teaching (EVALON).
      This evaluation is designed to be an objective benchmarking tool which is used
      for the distribution of university funds. It is also a steering instrument for
      direct improvement of teaching in clinical subjects. The aim of this study was to
      investigate, whether EVALON improved the quality of teaching between 2006 and
      2010 and whether the department of anesthesiology improved its ranking in
      comparison with the other participating institutes. MATERIALS AND METHODS: Data
      from the EVALON questionnaire from the years 2006-2010 were analyzed for
      improvements in the quality of teaching in anesthesiology. This study focused on
      three essential contents of the EVALON questionnaire (structural content and
      organizational procedure of lectures and seminars, course presentation), which
      were used for the generation of a ranking list of all participating medical
      institutes and departments. On the basis of these results, 12.5% of the funding
      was assigned for educational purposes. RESULTS: There was an average return rate
      of the questionnaires of 74.5%. A significant increase in the overall assessment
      score of 43.4% could be observed from 5.3 in the summer semester of 2006 to 7.6
      in the winter semester of 2009/10. The evaluation score for the department of
      anesthesiology concerning structural content of seminars and lectures increased
      by 79% from 4.8 in 2006 to 8.6 in 2010. The quality of organizational procedure
      was evaluated with a score of 4.9 in 2006 and improved by 74% to 8.5 in 2010. The
      course presentation skills of the teachers as evaluated by EVALON improved by 61%
      from a score of 5.2 in 2006 to 8.4 in 2010. In comparison with all other
      participating medical institutes the department of anesthesiology improved its
      ranking from position 36 in the winter semester 2006 to position 2 in the summer
      semester 2010. CONCLUSIONS: The reorganization of teaching anesthesiology,
      directly controlled by the results of EVALON improved the ranking of the
      department of anesthesiology. There was also a concomitant increase of the
      performance-oriented allocation of funds assigned to the department of
      anesthesiology based on the EVALON results.

PMID- 22653094
TI  - Eperisone versus tizanidine for treatment of chronic low back pain.
AB  - AIM: Many therapies exist for treatment of chronic low-back pain (LBP) including
      the use of muscle relaxant and analgesic drugs. The aim of this paper was to
      compare efficacy and tolerability of eperisone and tizanidine in combination
      treatment with tramadol in chronic LBP. METHODS: Sixty patients affected by
      chronic LBP associated with contractures of paravertebral muscles were randomized
      in two groups: Group E (30 patients) treated with eperisone; Group T (30
      patients) treated with tizanidine. Both groups received tramadol retard 100
      mg/day. VAS at rest and with effort were used at baseline (T0) and after 5 (T5),
      10 (T10), 15 (T15) and 30 (T30) days of treatment. The Summed Pain Intensity
      Difference (SPID), the SPID percentage (SPID%) and the Total Pain Relief
      (TOTPAR), at rest (-r) and with effort (-e) were calculated. RESULTS: In both
      groups a statistically significant reduction in VAS-r and VAS-e was observed
      during the treatment; similar reductions occurred in both groups at every
      timepoint. SPID-r and -e, SPID%-r and -e and TOTPAR-r and -e resulted similar
      between groups. A significant difference between groups occurred for incidence of
      somnolence: 16.6% for Group E versus 43.3% for Group T. Treatment was stopped due
      to adverse events in 5 patients of Group E and in 9 patients of Group T, without
      statistically significant difference. CONCLUSION: Both associations assumed for
      one month, have shown effective for LBP at rest and with effort.
      Eperisone/tramadol, reducing discontinuation and allowing a better adherence to
      the therapy, may be considered a viable option for the treatment of chronic LBP.

PMID- 22653095
TI  - Identification of Wnt pathway, uPA, PAI-1, MT1-MMP, S100A4 and CXCR4 associated
      with enhanced metastasis of human large cell lung cancer by DNA microarray.
AB  - AIM: The aim of this paper was to investigate the differentially expressed genes
      in large cell lung cancer cell lines with different metastatic potential, and to
      screen out new candidate genes related to metastasis of lung cancer. METHODS: The
      total RNAs of low and high metastatic large cell lung cancer cell lines (NL9980
      and L9981) were extracted and processed, then hybridized to Affymetrix HG U133
      Plus 2.0 array. The hybridization signals were scanned and compared to find out
      the differentially expressed genes. Chosen genes were verified by Western Blot.
      Bioinformatics were used to analyze the functions and related pathways of the
      genes. RESULTS: There were 933 differentially expressed genes between NL9980 and
      L9981 cell lines. In the high metastatic cell line L9981, 672 genes were up
      regulated and 260 genes were down-regulated compared with the low metastatic cell
      line NL9980. The differentially expressed genes were mainly associated with
      binding, catalytic activity, signal transducer activity and transporter activity,
      and mainly involved in pathways including, pathways in cancer, focal adhesion,
      regulation of actin cytoskeleton, ECM-receptor interaction. CONCLUSION:
      Differentially expressed genes with the functions including binding, catalytic
      activity, signal transducer activity and transporter activity may promote
      metastasis of lung cancer cells through complicated networks including Wnt
      pathway and metastasis-related genes such as uPA, PAI-1, MT1-MMP, S100A4 and
      CXCR4.

PMID- 22653097
TI  - [Study of codeine-paracetamol combination treatment compared with tramadol
      paracetamol in the control of moderate-to-severe low back pain].
AB  - AIM: The objective of this study was to compare the analgesic efficacy and
      tolerability of tramadol hydrochloride compared with codeine phosphate in
      combination with paracetamol in patients with moderate-to-severe low back pain
      caused by osteoarthritis. In fact, while paracetamol is the analgesic of choice
      for this disease, in cases where this treatment may be ineffective, the
      therapeutic choice involves the addition of weak opioids. Due to the chronic
      nature of the disease, these drugs represent a safer alternative compared to anti
      inflammatory drugs (NSAIDs) and selective inhibitors of cyclooxygenase 2 (COX-2).
      METHODS: In the present study two combination treatments were considered: codeine
      paracetamol (respectively 30 mg and 500 mg) and tramadol-paracetamol
      (respectively 37.5 mg and 325 mg). The study duration was 4 weeks and involved 38
      patients (mean age 64.7 years). The effectiveness of the two treatments was
      assessed in terms of analgesic efficacy, tolerability and safety. RESULTS: The
      results recorded after a week of treatment and at the end of the study showed a
      difference in favour of codeine-paracetamol association which showed slightly
      higher values in pain improvement and, above all, was better tolerated in terms
      of adverse events and drop out. CONCLUSION: The study, although conducted on a
      limited number of patients and for a relatively short time, demonstrates the
      greater efficacy and tolerability of the association codeine-paracetamol compared
      to tramadol-paracetamol.

PMID- 22653096
TI  - Mutual role of PGRN/TNF-alpha on osteopenia developing in obesity's inflammation
      state.
AB  - AIM: The aim of the study was to investigate the concentration of PGRN and other
      inflammatory cytokines TNF-alpha, IL-1beta, IL-4, IL-6, IL-10, IL-13 and IL-17 in
      osteopenic and non-osteopenic obese subjects. Bone mineral density in subjects
      with different PGRN levels were compared to the appraisal of our hypothesis.
      METHODS: A total of 171 obese participants (BMI >=30) were included in the study.
      Analysis of body composition was performed with use of Body Composition Analyzer.
      All blood samples were collected between 8:00 and 10:00 a.m. following an
      overnight fasting. The circulating levels of TNF-alpha, PGRN, IL-1beta, IL-4, IL
      6, IL-10, IL-13, IL-17, PTH, 25-Hydroxy Vitamin D and crosslaps were measured
      with the EIA method. BMD was measured by use of dual energy X-ray absorptiometery
      (DXA) at lumbar spine (vertebrae L2-L4) and hip level. Participants were
      categorized into osteopenic and healthy group according to the World Health
      Organization (WHO) criteria. Of 171 participants, 51 (29.82 %) were osteopenic
      and 120 (70.17%) were healthy. RESULTS: We found significantly higher
      concentrations of crosslaps, IL-17, IL-6, TNFalpha and IL-4 and lower
      concentrations of IL-13, IL-10, PGRN and free fat mass in osteopenic group. With
      raising the PGRN level, the concentrations of IL-13, IL-10 and 25-(OH) vitamin D
      were increased and the concentration of TNFalpha and IL-17 were decreased. Our
      results demonstrated that the density of bone at both sites of lumbar spine (L2
      L4) and hip region was highest in 4th quartile and lowest in first quartile of
      categorized PGRN concentration. The bone status was gradually improved with
      raising the PGRN level in parallel at lumbar spine (L2-L4) and hip regions.
      CONCLUSION: Based on the pathway of effect of TNFalpha on bone metabolism, it
      appears that PGRN acts on the bone with mechanisms involving TNFR signaling,
      disturbance and TNFalpha performance, similar to the results that have been found
      in animal model study.

PMID- 22653098
TI  - IgG-anti-IgA antibodies: an autoimmune finding in patients with psoriasis
      vulgaris.
AB  - AIM: Psoriasis is thought to be an autoimmune disease caused by inappropriate
      activation of the cellular immune system. In this study, we aimed to search out
      IgG-anti-IgA antibody levels, serum immunoglobulins and antinuclear antibodies
      (ANA). METHODS: The study enrolled 38 psoriasis vulgaris patients and 40 healthy
      controls. RESULTS: Mean IgG-anti-IgA levels were significantly higher in
      psoriasis patients. The frequency of positive ANA testing was 21.1%; however,
      there was no correlation between IgG-anti-IgA antibody levels and ANA positivity.
      Only one patient had low IgA levels without high IgG-anti-IgA concentrations.
      CONCLUSION: The data about high IgG-anti-IgA antibody levels are noteworthy for a
      new evidence of autoimmune mechanism.

PMID- 22653099
TI  - Is there any relationship between pulmonary function tests and post-transplant
      complications of allogeneic hematopoetic stem cell transplantation?
AB  - AIM: Pulmonary function tests (PFT) have an important role in the assessment of
      pulmonary and nonpulmonary complications of hematopoetic stem cell
      transplantation (HSCT). In this study the relationship between PFTs and DLCOadj
      values and the complications of HSCT was investigated. The possible role of iron
      overload in the deterioration of the PFTs after HSCT was also searched. METHODS:
      One hundred and fifty one patients who had undergone allogeneic HSCT between
      years 2003 through 2008, and had the records of PFTs prior to and at 1, 3, 6, 9
      and 12 months after transplantation were included in the study. Prospectively
      collected data of these patients were analysed retrospectively. RESULTS: Although
      no significant difference was identified in other PFT parameters, a significant
      decrease in DLCOadj was determined after 1st and 3rd months of HSCT. A
      significant correlation was found between pretransplant DLCOadj value <%70 and
      sinusoidal obstruction syndrome (SOS) (P=0.001, r=0.323), but in multivariate
      analysis pretransplant DLCOadj was not an independent predictor of SOS; only
      total body irradiation (TBI) (OR: 3.673, %95 CI: 0.880-15.804), the day of
      platelet engraftment (OR=1.093, %95 CI: 1.029-1.161) and serum ferritin
      (OR=1.001, %95 CI: 1.000-1.001) were significant. Advancing age and serum
      ferritin levels >600 ng/mL were the independent risk factors for pretransplant
      DLCOadj <%70 (OR: 0.970, %95 CI: 0.941-0.999 and OR: 2.355, %95 CI: 1.058-5.241
      respectively). CONCLUSION: Although a significant correlation exists between
      pretransplant DLCOadj values and post-transplant SOS development, pretransplant
      DLCOadj was not an independent predictor of SOS. Increased serum ferritin levels
      were common both for pretransplant DLCO decrease and post-transplant SOS
      development. Iron induced endothelial damage may be the common pathophysiologic
      mechanism causing lung and liver vulnerability, and DLCOadj may be a non-invasive
      method of demonstrating this vulnerability.

PMID- 22653100
TI  - Patent foramen ovale and ischemic stroke.
AB  - Patent foramen ovale (PFO) is a common finding in healthy subjects and has not
      been associated with increased risk of ischemic stroke in population-based cohort
      studies. Nevertheless, case-control studies have consistently shown an increased
      prevalence of PFO in cryptogenic stroke, suggesting that PFO might be a cause of
      stroke. The risk of stroke recurrence in patients with cryptogenic stroke and PFO
      is low under aspirin therapy but may be substantially higher in patients with an
      associated atrial septal aneurysm (ASA). The mechanisms of stroke associated with
      PFO or ASA are uncertain. Paradoxical embolism through the PFO is rarely
      documented. The optimal treatment for secondary prevention in patients with
      cryptogenic stroke and PFO is still uncertain and debated. A randomized
      controlled trial failed to demonstrate the superiority of transcatheter PFO
      closure over medical therapy. Whether anticoagulation is superior to aspirin
      should be tested in a randomized controlled trial.

PMID- 22653102
TI  - Nonlinearity exponent of ac conductivity in disordered systems.
AB  - We measured the real part of ac conductance Sigma(x,f) or Sigma(T,f) of iron
      doped mixed-valent polycrystalline manganite oxides LaMn(1-x)Fe(x)O(3) as a
      function of frequency f by varying initial conductance Sigma(0) by quenched
      disorder x at a fixed temperature T (room) and by temperature T at a fixed
      quenched disorder x. At a fixed temperature T, Sigma(x,f) of a sample with fixed
      x remains almost constant at its zero-frequency dc value Sigma(0) at lower
      frequency. With increase in f, Sigma(x,f) increases slowly from Sigma(0) and
      finally increases rapidly following a power law with an exponent s at high
      frequency. Scaled appropriately, the data for Sigma(T,f) and Sigma(x,f) fall on
      the same universal curve, indicating the existence of a general scaling formalism
      for the ac conductivity in disordered systems. The characteristic frequency f(c)
      at which Sigma(x,f) or Sigma(T,f) increases for the first time from Sigma(0)
      scales with initial conductance Sigma(0) as f(c) ~ Sigma(0)(x(f)), where x(f) is
      the onset exponent. The value of x(f) is nearly equal to one and is found to be
      independent of x and T. Further, an inverse relationship between x(f) and s
      provides a self-consistency check of the systematic description of Sigma(x,f) or
      Sigma(T,f). This apparent universal value of x(f) is discussed within the
      framework of existing theoretical models and scaling theories. The relevance to
      other similar disordered systems is also highlighted.

PMID- 22653101
TI  - [Radiometabolic therapy for metastatic thyroid carcinoma: overview of the
      literature and rational bases for the use of recombinant human TSH].
AB  - The established treatment for differentiated thyroid carcinoma (DTC) is founded
      on total thyroidectomy and subsequent administration of radioiodine (131I) to
      ablate the thyroid remnant and to treat the metastatic disease. In the case of
      metastatic or recurrent disease, further cycles of 131I therapy are often
      necessary. The condition for maximizing the effectiveness of the treatment is to
      have an adequate stimulation from TSH, which must be >25-30 mIU/L. This elevation
      is achieved either discontinuing the hormone suppression therapy for an
      appropriate period, or administering recombinant human TSH (rhTSH). The latter
      has shown good clinical efficacy in patients with residual thyroid gland and is
      nowadays commonly employed since it is easy to use and allows to avoid the side
      effects of hypothyroidism. It thus represents a good alternative to thyroid
      hormone withdrawal for the remnant ablation, while is still open the question if
      its efficacy on the management of metastatic disease is superimposable to thyroid
      hormone withdrawal. To this purpose, a Panel of expert reviewed the literature,
      assessing the advantages and disadvantages for the patient, as well as the impact
      in terms of cost and benefit to the National Health Service. The work of the
      Panel concluded with a proposal for the use of rhTSH in selected patients with
      metastatic DTC, in which is considered the efficacy and safety of the product and
      is examined its use in terms of costs; this proposal was accepted by the Italian
      Drug Agency resulting in an update of the indications for rhTSH.

PMID- 22653103
TI  - Measuring the Cobb angle with the iPhone in kyphoses: a reliability study.
AB  - PURPOSE: Smartphones have gained widespread use in the healthcare field to
      fulfill a variety of tasks. We developed a small iPhone application to take
      advantage of the built-in position sensor to measure angles in a variety of
      spinal deformities. We present a reliability study of this tool in measuring
      kyphotic angles. METHODS: Radiographs taken from 20 different patients' charts
      were presented to a panel of six operators at two different times. Radiographs
      were measured with the protractor and the iPhone application and statistical
      analysis was applied to measure intraclass correlation coefficients between both
      measurement methods, and to measure intra- and interobserver reliability RESULTS:
      The intraclass correlation coefficient calculated between methods (i.e. CobbMeter
      application on the iPhone versus standard method with the protractor) was 0.963
      for all measures, indicating excellent correlation was obtained between the
      CobbMeter application and the standard method. The interobserver correlation
      coefficient was 0.965. The intraobserver ICC was 0.977, indicating excellent
      reproductibility of measurements at different times for all operators. The
      interobserver ICC between fellowship trained senior surgeons and general
      orthopaedic residents was 0.989. Consistently, the ICC for intraobserver and
      interobserver correlations was higher with the CobbMeter application than with
      the regular protractor method. This difference was not statistically significant.
      CONCLUSION: Measuring kyphotic angles with the iPhone application appears to be a
      valid procedure and is in no way inferior to the standard way of measuring the
      Cobb angle in kyphotic deformities.

PMID- 22653114
TI  - Liver enzyme and adipocytokine profiles are synergistically associated with
      insulin resistance: the J-SHIPP study.
AB  - AIM: Alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are
      associated with insulin resistance and arteriosclerotic disease. Since adiposity
      raises liver enzyme levels and causes insulin resistance, adipocytokines are
      thought to underlie the relationship between liver enzymes and insulin
      resistance. To clarify this hypothesis, we conducted a cross-sectional
      epidemiological study in a Japanese general population. METHODS: The study
      subjects were 903 middle-aged to elderly persons. Plasma levels of adiponectin
      and leptin were measured, while other clinical parameters were obtained from
      personal health records of medical check-ups. Insulin resistance was assessed by
      a homeostasis model assessment index (HOMA-IR). RESULTS: Plasma levels of ALT
      (r=0.379, p<0.001), GGT (r=0.225, p<0.001), adiponectin (r= -0.346, p<0.001) and
      leptin (r=0.369, p<0.001) were significantly correlated with insulin resistance
      even on subgroup analysis by sex. Further, any combination of liver enzymes and
      adipocytokines was synergistically associated with insulin resistance (p<0.001)
      after adjustment for possible covariates (ALT*adiponectin: beta=-0.098, p<0.001,
      ALT*leptin: beta=0.129, p<0.001, GGT*adiponectin: beta=-0.054, p=0.054,
      GGT*leptin: beta=0.126, p<0.001); however, in simple obese subjects with normal
      adipocytokine levels, liver enzymes were not associated with insulin resistance
      (mean HOMA-IR: worsened adipocytokine +/visceral obesity +, 2.01+/-1.14; +/-,
      1.39+/-0.84; -/+, 1.23+/- 0.55; -/-, 1.03+/-0.57; p<0.001). CONCLUSION: Plasma
      levels of ALT and GGT were independent determinants of insulin resistance only in
      subjects with a worsened adipocytokine profile. Use of liver enzyme levels as a
      marker of insulin resistance requires stratification by adipocytokine profile.

PMID- 22653115
TI  - Current world literature.

PMID- 22653118
TI  - Template-free electrodeposition of highly oriented and aspect-ratio controlled
      ZnO hexagonal columnar arrays.
AB  - We report an easy one-step template-free electrodeposition method for preparing
      large arrays of ZnO hexagonal nanocolumns, vertically oriented on a Au-coated Si
      substrate. Systematic scanning electron microscopy investigations revealed the
      potential of this method for obtaining a high degree of verticality and
      orientation of the nanostructures and for controlling their aspect-ratio in an
      easy manner. Further structural studies demonstrated that the as-obtained ZnO
      nanocolumns present a well defined hexagonal symmetry exhibiting an excellent
      crystallinity.

PMID- 22653117
TI  - Versatile robotic interface to evaluate, enable and train locomotion and balance
      after neuromotor disorders.
AB  - Central nervous system (CNS) disorders distinctly impair locomotor pattern
      generation and balance, but technical limitations prevent independent assessment
      and rehabilitation of these subfunctions. Here we introduce a versatile robotic
      interface to evaluate, enable and train pattern generation and balance
      independently during natural walking behaviors in rats. In evaluation mode, the
      robotic interface affords detailed assessments of pattern generation and dynamic
      equilibrium after spinal cord injury (SCI) and stroke. In enabling mode,the robot
      acts as a propulsive or postural neuroprosthesis that instantly promotes
      unexpected locomotor capacities including overground walking after complete SCI,
      stair climbing following partial SCI and precise paw placement shortly after
      stroke. In training mode, robot-enabled rehabilitation, epidural electrical
      stimulation and monoamine agonists reestablish weight-supported locomotion,
      coordinated steering and balance in rats with a paralyzing SCI. This new robotic
      technology and associated concepts have broad implications for both assessing and
      restoring motor functions after CNS disorders, both in animals and in humans.

PMID- 22653120
TI  - Allergic contact dermatitis and patch-testing education in US dermatology
      residencies in 2010.
AB  - BACKGROUND: The state of allergic contact dermatitis (ACD) education has not been
      formally examined since the original study done by High and Cruz (Am J Contact
      Dermat. 2003;14(4):195-199). OBJECTIVE: The objectives of the study were to
      characterize the current state of ACD and patch-testing education in US
      dermatology residency programs and to determine if there has been any significant
      improvement over the past 8 years. METHOD: This was a survey of ACD education and
      patch-testing practices in US dermatology residency programs. RESULTS: Surveys
      were sent to program directors and chief residents at all 112 US dermatology
      residency programs. Of the 224 surveys sent out, 105 (46.88%) were returned.
      There were several statistically significant changes from the 2002 survey. More
      faculty members who are designated as ACD experts are now members of the American
      Contact Dermatitis Society. Fewer programs now routinely review contact
      dermatitis-specific journals. Residents are now more likely to receive didactic
      lectures on ACD. Program directors estimated graduating residents will now be
      less likely to perform the TRUE Test in practice, and although not statistically
      significant, program directors also estimated an increase in the number of
      residents who will use expanded tests. CONCLUSIONS: Although some areas of ACD
      education have improved over the past 8 years, opportunities to further improve
      remain.

PMID- 22653121
TI  - Clinically relevant patch test results in patients with burning mouth syndrome.
AB  - BACKGROUND: Patients with a sore or burning mouth associated with clinically
      normal oral mucosa present a difficult diagnostic challenge. OBJECTIVE: The
      objective of this study was to assess the value of patch testing in patients with
      burning mouth syndrome. METHODS: We retrospectively reviewed the results of patch
      testing to an oral series in patients with burning mouth syndrome seen at Mayo
      Clinic, Rochester, Minnesota, between January 2000 and April 2006. RESULTS: Of
      195 consecutive patients with a burning or sore mouth, 75 had patch testing to an
      oral series, and 28 of these patients (37.3%) had allergic patch test reactions.
      The most common allergens were nickel sulfate hexahydrate 2.5%, balsam of Peru,
      and gold sodium thiosulfate 0.5%. On follow-up, 15 patients reported improvement,
      4 removed or avoided the offending dental metal, and 6 avoided the dietary
      allergen. Thirteen patients did not improve; 6 avoided identified allergens, but
      without improvement; 1 removed dental metals without symptom change; and 5
      avoided test-positive dietary allergens but without improvement. The remaining 7
      nonresponders had nonrelevant patch test results or did not avoid allergens.
      CONCLUSIONS: Patch testing can identify patients who may be allergic to dental
      metals or dietary additives and who may benefit from removal or avoidance of
      these.

PMID- 22653122
TI  - Patch tests with fragrance mix II and its components.
AB  - BACKGROUND: Fragrance mix II (FM II) was initiated to detect contact
      hypersenstitivity (CH) to fragrances that could not have been identified
      previously. OBJECTIVE: The aim of this multicenter study was to map the frequency
      of CH to FM II and its components in Hungary. METHODS: Six centers participated
      in the survey from 2009 to 2010. A total off 565 patients (434 women and 131 men)
      with former skin symptoms provoked by scented products were patch tested. The
      tests were performed with Brial GmbH D-Greven allergens. In the environmental
      patch test series, FM II, FM I, Myroxylon pereirae, colophonium, wood-tar mix,
      propolis, and sesquiterpene lactone mix were tested as fragrance allergens. The
      FM II components (citral, farnesol, coumarin, citronellol, alpha-hexyl
      cinnamaldehyde, and hydroxy-isohexyl-3-cyclohexene-carboxaldehyde [Lyral]) were
      also tested. RESULTS: Contact hypersenstitivity to any fragrances was detected in
      28.8%, to FM II in 17.2% of the patients. Contact hypersenstitivity to hydroxy
      isohexyl-3-cyclohexene-carboxaldehyde was observed in 7.3%, to coumarin in 5.1%,
      to alpha-hexyl-cinnamaldehyde in 3.5%, to citral in 3.4%, to farnesol in 2.5%,
      and to citronellol in 1.2%. Of the FM II-positive cases, 48.4% showed isolated CH
      reaction. CONCLUSIONS: The frequency of CH to FM II is 17.2% in the tested,
      selected Hungarian population. The CH to FM II and its components could not have
      been revealed without the present test materials.

PMID- 22653123
TI  - Climatotherapy at the Dead Sea: an effective treatment modality for atopic
      dermatitis with significant positive impact on quality of life.
AB  - BACKGROUND: Atopic dermatitis (AD) has an appreciable effect on quality of life.
      Improving the quality of life of AD patients is a priority. OBJECTIVE: This study
      aimed to evaluate the impact of Dead Sea climatotherapy (DSC) as a treatment of
      AD and its influence on the quality of life of these patients. METHODS: Forty
      nine adult patients with AD treated during the years 2009-2010 at the Deutsches
      Medizinisches Zentrum Medical Center participated in this prospective study.
      Climatotherapy was administered in accordance with a computer-designed protocol
      and included gradually increased sun exposure after a sea bath. Severity of AD
      was evaluated using the Scoring Atopic Dermatitis (SCORAD) index. Patient quality
      of life was evaluated using Skindex-29. Statistical analysis was performed using
      a paired t test and Wilcoxon and Mann-Whitney U tests. RESULTS: After treatment,
      the mean SCORAD value improved by 39 points (P < 0.001). The overall Skindex-29
      score improved by a mean value of 33 points (P < 0.001). The pretreatment SCORAD,
      duration of AD, and maximal daily sun exposure predicted the posttreatment SCORAD
      values. Pretreatment Skindex-29 and patient age predicted the posttreatment
      Skindex-29 in a multiple linear regression model. CONCLUSIONS: Dead Sea
      climatotherapy provides an effective treatment modality for AD by improving the
      patient's skin condition and quality of life.

PMID- 22653124
TI  - Prevalence of cutaneous adverse drug reactions in Southwest China: an 11-year
      retrospective survey on in-patients of a dermatology ward.
AB  - BACKGROUND: An update of the information about the prevailing trend of cutaneous
      adverse drug reactions (CADRs) is important for clinicians. OBJECTIVE: The
      objective of the study was to survey the prevalence of CADRs in Southwest China
      over the past 11 years. METHODS: The clinical and laboratory data of all
      inpatients admitted with a diagnosis of CADRs to the dermatology ward of
      Southwest Hospital during the past 11 years were retrospectively investigated.
      RESULTS: In the 547 recruited patients, the most common clinical pattern was
      maculopapular eruptions (n = 277), followed by fixed drug eruptions (n = 84) and
      acute urticaria (n = 44). In 206 cases with single medication intake, the 3 most
      common culprit drugs were acetaminophen (n = 44), penicillins (n = 44), and
      cephalosporins (n = 30). The frequency of urticaria in the elderly (>=60 years
      old) (n = 117) was significantly lower than that in younger patients (<60 years
      old) (n = 430) (P = 0.046), whereas erythema multiforme was much more common in
      the elderly (P = 0.038). As compared with younger patients, allopurinol was the
      most common culprit drug in the elderly. CONCLUSIONS: In contrast to previous
      studies, our study showed that the prevalence profiles of CADRs in the elderly
      are quite different from those in younger population. Acetaminophen was the most
      common culprit drug for total CADRs, which should be alerted as an important
      public health problem.

PMID- 22653125
TI  - p-tert-Butylphenol formaldehyde resin and its impact on children.
AB  - : p-tert-Butylphenol formaldehyde resin (PTBPFR) is widely used as an adhesive
      owing to its rapid onset of action, durability, flexibility, and heat resistance.
      Moreover, because of its tackiness, it is particularly useful as a glue component
      on both leather and rubber products. Sensitization to this resin has been
      increasing since the first cases of PTBPFR contact allergy in the late 1950s, and
      pediatric contact allergy to this resin is a significant problem. p-tert
      Butylphenol formaldehyde resin has been reported as a leading cause of shoe
      associated dermatitis internationally, as well as a cause of allergic contact
      dermatitis from its use in neoprene wet suits and sports equipment such as shin
      guards. In summary, patch test screening of both adults and children with PTBPFR
      is important, given the ubiquitous use of this chemical.

PMID- 22653126
TI  - Sesquiterpene lactone-related allergic contact dermatitis after exposure to tulip
      poplar wood and bark.

PMID- 22653127
TI  - Butylhydroxytoluene--from jet fuels to cosmetics?

PMID- 22653129
TI  - Allergy to jasmine is not always delayed contact allergy.

PMID- 22653128
TI  - Contact dermatitis following exposure to bird excrement.

PMID- 22653130
TI  - Allergic contact dermatitis induced by topical hydrocortisone-17-butyrate
      mimicking papular rosacea.

PMID- 22653132
TI  - Blue contact urticaria.

PMID- 22653131
TI  - Contact allergy to a permanent marker.

PMID- 22653133
TI  - Recall dermatitis at patch test sites in alopecia areata treated with
      diphencyprone.

PMID- 22653134
TI  - Acute generalized exanthematous pustulosis associated with acyclovir, confirmed
      by patch testing.

PMID- 22653135
TI  - Influence of antipsychotic agents on heart rate variability in male WKY rats:
      implications for cardiovascular safety.
AB  - BACKGROUND: Sudden cardiac death is higher among schizophrenic patients and is
      associated with parasympathetic hypoactivity. Antipsychotic agents are highly
      suspected to be a precipitating factor. Thus, we aimed to test if the
      antipsychotics haloperidol, risperidone and clozapine affect cardiac autonomic
      function, excluding the confounding effect of altered sleep structure by the
      drugs. METHODS: In this study, haloperidol, risperidone and clozapine were given
      separately by intraperitoneal injection to male Wistar-Kyoto rats for 5 days.
      Electroencephalogram (EEG), electromyogram (EMG) and electrocardiographic signals
      were recorded at baseline and 5 days after drug treatments. Sleep scoring was
      based on EEG and EMG signals. Cardiac autonomic function was assessed using heart
      rate variability analysis. RESULTS: Clozapine increased heart rate and suppressed
      cardiac sympathetic and parasympathetic activity. Cardiac acceleration was more
      severe during sleep. Haloperidol tended to decrease heart rate while risperidone
      mildly increased heart rate; however, their effects were less obvious than those
      of clozapine. There was a significant drug-by-stage interaction on several heart
      rate variability measures. CONCLUSION: Taking this evidence as a whole, we
      conclude that haloperidol has a better level of cardiovascular safety than either
      risperidone or clozapine. Application of this approach to other psychotropic
      agents in the future will be a useful and helpful way to evaluate the
      cardiovascular safety of the various psychotropic medications that are in
      clinical use.

PMID- 22653136
TI  - Damage- and pathogen-associated molecular patterns and alarmins: keys to sepsis?.
AB  - The concept that sepsis is the result of an uncontrolled inflammatory response of
      the host's innate immune system towards invading pathogens has recently been
      challenged. Evidence is accumulating that, in addition, host-derived alarm
      molecules are released during sepsis- and trauma-associated cell death, thus
      triggering the host's immune response. The identification and characterization of
      exogenous as well as endogenous danger molecules allowed significant advances in
      our understanding of the pathophysiology of sepsis and may provide potential
      targets for therapeutic interventions.

PMID- 22653137
TI  - [Minimally invasive adrenal gland surgery. Transperitoneal or retroperitoneal
      approach?].
AB  - Currently adrenal gland surgery can be performed by a variety of laparoscopic and
      retroperitoneoscopic approaches. Of particular importance are the lateral
      laparoscopic and posterior retroperitoneoscopic approaches. Comparative studies
      of transperitoneal and retroperitoneal adrenalectomy demonstrate heterogeneous
      results. Nevertheless, retroperitoneal techniques may offer less postoperative
      pain and faster recovery. All these minimally invasive techniques are safe and
      reliable and have replaced open approaches in most cases.

PMID- 22653138
TI  - [Death on the operating table and death in the early post-operative period :
      recommendations of forensic pathologists].
AB  - Death during an operation represents a severe event for physicians and family of
      the deceased. A further difficulty arises when certifying the cause and manner of
      death because medical staff are often afraid that they will incriminate
      themselves when declaring an unnatural death or an unclear manner of death but
      are also afraid to issue a false statement by declaring a natural death. In such
      cases of mors in tabula it is recommended to declare an unclear manner of death
      because this leads to police investigations and in the majority of the cases to
      exoneration of the medical staff.

PMID- 22653139
TI  - [Surgical management of a retrorectal tumor with consideration of a rare
      differential diagnosis].
AB  - We present a case of a retrorectal space occupying lesion diagnosed as an
      adenocarcinoma of unknown primary origin by preoperative histopathology.
      Localization slightly above the anal sphincter would have required extirpation of
      the rectum. Rectal palpation, endosonography and radiological imaging, however,
      suggested a retrorectal tumor or a metastasis of an adenocarcinoma. Both entities
      would have required local resection. We applied a surgical algorithm including
      frozen biopsy allowing a stepwise choice of operative procedure from the spectrum
      in question. The operation performed was thus tailored to the entity of the
      tumor.

PMID- 22653141
TI  - Comparison of breast augmentation incisions and common complications.
AB  - BACKGROUND: Incisions for insertion of breast implants are most commonly placed
      in the inframammary fold, areola, or axilla. Previous studies have evaluated
      selection of incision location preoperatively and for nipple-areola complex
      sensation retention after primary augmentation mammaplasty. This study compares
      the most common postoperative complications for each incision location in
      patients who underwent primary breast augmentation. METHODS: A retrospective
      chart review was performed on 619 patients who underwent primary breast
      augmentation, excluding simultaneous mastopexy, within a single group practice
      from July 1994 to June 2009. Incision location, postoperative complications
      (capsular contracture, hematoma formation, rippling, infection, and rupture), and
      total reoperation rates were recorded. Incision locations were also compared with
      respect to implant fill type (saline or silicone gel) and pocket location
      (subglandular or submuscular). RESULTS: A statistically significant association
      was identified between total reoperation and incision location (p = 0.0054). The
      highest rate of total reoperation occurred when using an inframammary fold
      incision compared to either the transaxillary or periareolar. This relationship
      with total reoperation was not attributed to the five complications analyzed, but
      rather with patient desire for size/style change, asymmetry, or ptosis. No
      statistically significant association was observed between incision location and
      specific complications such as capsular contracture, rippling, implant rupture,
      hematoma, or infection. CONCLUSIONS: None of the five complications analyzed
      correlated with incision location. The data generated from this study will assure
      the surgeon that all three incision locations are safe. Preoperative examination,
      patient preference, and surgeon comfort should remain the mainstays of incision
      planning in augmentation mammaplasty. LEVEL OF EVIDENCE IV: This journal requires
      that authors assign a level of evidence to each article.

PMID- 22653142
TI  - Endoscopically assisted aesthetic augmentation of tuberous breasts and fat
      grafting to correct the double bubble.
AB  - BACKGROUND: Treatment of tuberous breasts types 1 and 2 must deal with the
      problem of the pseudo-double bubble in the primitive inframammary fold and also
      must release the constrictive ring. Two techniques currently are used to overcome
      these problems, but neither is entirely satisfactory. The first technique, in
      which the approach is via the primitive inframammary fold, leaves significant
      scarring when the lower poles expand. The second technique, in which the approach
      is periareolar, considerably reduces the area's sensitivity. This report presents
      a new endoscopically assisted technique with an axillary approach designed to
      solve these problems. METHODS: Between 2005 and 2010, 68 patients (ages 18-42
      years) underwent surgery. The intervention was bilateral in 57 and unilateral in
      11 of these patients. All cases involved tuberous breasts types 1 and 2
      (Grolleau's classification). The augmentation involves a transaxillary subfascial
      endoscopic approach, opening of the fascia at the primitive inframammary fold,
      and releasing of the constricting ring to enable the breast to expand, followed
      by implantation of an anatomic prosthesis to add volume to the lower quadrants.
      If the pseudo-double bubble appears, fat grafting is applied during the same
      surgical procedure. RESULTS: The results were reported to be highly satisfactory
      both by the patients and by the independent medical team. For six patients (8.82
      %), fat grafting had to be repeated in the double bubble. No major complications
      were reported. CONCLUSION: The endoscopically assisted subfascial breast
      augmentation technique obtains highly satisfactory results in tuberous breasts
      types 1 and 2 (Grolleau's classification). The single scar is concealed in the
      axillary fold. LEVEL OF EVIDENCE IV: This journal requires that authors assign a
      level of evidence to each article.

PMID- 22653143
TI  - Huge recurrent tumoral calcinosis needing extensive excision and reconstruction:
      report of a rare case and brief literature review.
AB  - Tumoral calcinosis, a rare benign clinical condition resembling a neoplasm, is
      characterized by calcium deposits, usually located in the soft tissues around the
      large joints. It can be primary or secondary to renal failure and
      hyperparathyroidism. This report describes an unusual case of recurrent tumoral
      calcinosis presenting as a huge mass infiltrating the skin and muscles of the
      lumbosacral area. The patient underwent wide excision and reconstruction with
      bilateral V-Y advancement gluteal fasciocutaneous flaps and at this writing
      remains disease free 4 years postoperatively. A concise review of the pertinent
      literature focusing on the diagnosis, treatment options, and preventive measures
      also is reported. LEVEL OF EVIDENCE V: This journal requires that authors assign
      a level of evidence to each article.

PMID- 22653144
TI  - NT5E CpG island methylation is a favourable breast cancer biomarker.
AB  - BACKGROUND: Relapse risk assessment and individual treatment recommendations
      remain suboptimal for breast cancer patients. In the light of existing
      preclinical and clinical data, we studied NT5E (5'-nucleotidase, ecto) expression
      and NT5E CpG island methylation in breast cancer. METHODS: We used RT-PCR, qPCR,
      methylation-specific PCR and pyrosequencing to analyse NT5E in breast carcinoma
      cell lines and primary and breast carcinomas. RESULTS: NT5E CpG island
      methylation was inversely associated with NT5E expression in breast carcinoma
      cell lines. In clinical series, patients whose primary tumours had NT5E CpG
      island methylation were less likely to develop metastasis (P=0.003, OR=0.34, 95%
      CI: 0.17-0.69). In 3/4 paired samples, NT5E was methylated in primary tumours and
      demethylated in CNS metastases. Patients progressing to non-visceral as compared
      with visceral metastases were more likely to have NT5E CpG island methylation in
      primary tumours (P=0.01, OR=11.8). Patients with tumours lacking detectable
      methylation had shorter disease-free survival (DFS) (P=0.001, HR=2.7) and overall
      survival (OS) (P=0.001, HR=3). The favourable prognostic value of NT5E
      methylation was confirmed in oestrogen receptor negative (P=0.011, HR=3.27, 95%
      CI: 1.31-8.12) and in triple negative cases (P=0.004; HR=6.2, 95% CI: 1.9-20).
      Moreover, we observed a more favourable outcome to adjuvant chemotherapy in
      patients whose tumours were positive for NT5E CpG island methylation: DFS
      (P=0.0016, HR=5.1, 95% CI: 1.8-14.37) and OS (P=0.0005, HR=7.4, 95% CI: 2.416
      23.08). CONCLUSION: NT5E CpG island methylation is a promising breast cancer
      biomarker.

PMID- 22653146
TI  - Pressure-induced enhancement of the superconducting properties of single
      crystalline FeTe0.5Se0.5.
AB  - The pressure dependence, up to 11.3 kbar, of basic parameters of the
      superconducting state, such as the critical temperature (T(c)), the lower and the
      upper critical fields, the coherence length, the penetration depth, and their
      anisotropy, was determined from magnetic measurements performed for two single
      crystalline samples of FeTe(0.5)Se(0.5). We have found pressure-induced
      enhancement of all of the superconducting state properties, which entails a
      growth of the density of superconducting carriers. However, we noticed a more
      pronounced increase in the superconducting carrier density under pressure than
      that in the critical temperature which may indicate an appearance of a mechanism
      limiting the increase of T(c) with pressure. We have observed that the critical
      current density increases under pressure by at least one order of magnitude.

PMID- 22653145
TI  - Fatty acid synthase expression associated with NAC1 is a potential therapeutic
      target in ovarian clear cell carcinomas.
AB  - BACKGROUND: This study examined the clinical significance of NAC1 and the
      expression level of its potential downstream target fatty acid synthase (FASN) in
      ovarian clear cell carcinomas (OCCCs), and evaluated the NAC1/FASN pathway as a
      potential therapeutic target. METHODS: NAC1 and FASN expression and NACC1 gene
      amplification were assessed in ovarian cancers by immunohistochemistry,
      fluorescence in situ hybridisation, and clinical data collected by a
      retrospective chart review. C75, a FASN inhibitor, was used to assess whether
      this pathway represented a therapeutic target in OCCC. RESULTS: High NAC1
      expression was most frequent in clear cell tumours (40.0%:24/60). NACC1 gene
      amplification was identified in none of the 58 OCCCs. The frequency of NACC1 gene
      amplification was significantly higher in the high-grade serous histology than in
      the clear cell histology (P<0.01). NAC1 expression was significantly correlated
      with FASN expression in both OCCC samples and OCCC cell lines. Either high NAC1
      expression or high FASN expression significantly correlated with shorter
      progression-free and overall survival (P=0.002 and 0.0048). NAC1 overexpression
      stimulated FASN expression, and NAC1 silencing using siRNA decreased FASN
      expression in OCCC cell lines. Profound growth inhibition was observed in C75
      treated carcinoma cells with FASN overexpression when compared with the response
      in carcinoma cells without FASN expression. CONCLUSION: These findings indicate
      that NAC1/FASN overexpression is critical to the growth and survival of a subset
      of OCCC. The FASN silencing by the C75-induced phenotypes depends on the
      expression status of the targeted cell line. Therefore, NAC1/FASN pathway
      targeted therapy may benefit selected OCCC patients.

PMID- 22653148
TI  - Current world literature.

PMID- 22653153
TI  - The synthesis and characterization of mono and dinuclear group 13 complexes
      derived from a Schiff base.
AB  - The coordination preferences of the tetradentate Schiff base, N,N'
      ethylenebis(acetylacetoimine), H(2)L, with a variety of group 13 precursors, led
      to the formation of a series of mono and binuclear products. The reaction of
      H(2)L with AlMe(3) and Me(2)GaCl afforded the binuclear complexes,
      [L{Al(Me)(2)}(2)] 1 and [H(2)L{GaCl(Me)(2)}(2)], 3, the latter an adduct of the
      neutral ligand. Treatment of 1 with iodine generated the cationic Al(III)
      complex, [LAl(thf)(2)]I, 2, while the addition of n-BuLi to H(2)L, followed by
      reaction with GaCl(3) and InCl(3) led to an ionic complex
      [{LGaCl}(2)(MULi)]GaCl(4), 4, an In(III) dimer, [LInCl](2), 5 and monomeric
      [LInCl(thf)], 6. In contrast, the reaction of [In{N(SiMe(3))(2)}(3)] with H(2)L
      yielded a homoleptic, air stable, indium complex, [L(3)In(2)], 7. All products
      were definitively characterized by X-ray crystallography and their structures
      confirmed by pertinent spectroscopic techniques.

PMID- 22653154
TI  - Realization of thermally durable close-packed 2D gold nanoparticle arrays using
      self-assembly and plasma etching.
AB  - Realization of thermally and chemically durable, ordered gold nanostructures
      using bottom-up self-assembly techniques are essential for applications in a wide
      range of areas including catalysis, energy generation, and sensing. Herein, we
      describe a modular process for realizing uniform arrays of gold nanoparticles,
      with interparticle spacings of 2 nm and above, by using RF plasma etching to
      remove ligands from self-assembled arrays of ligand-coated gold nanoparticles.
      Both nanoscale imaging and macroscale spectroscopic characterization techniques
      were used to determine the optimal conditions for plasma etching, namely RF
      power, operating pressure, duration of treatment, and type of gas. We then
      studied the effect of nanoparticle size, interparticle spacing, and type of
      substrate on the thermal durability of plasma-treated and untreated nanoparticle
      arrays. Plasma-treated arrays showed enhanced chemical and thermal durability, on
      account of the removal of ligands. To illustrate the application potential of the
      developed process, robust SERS (surface-enhanced Raman scattering) substrates
      were formed using plasma-treated arrays of silver-coated gold nanoparticles that
      had a silicon wafer or photopaper as the underlying support. The measured value
      of the average SERS enhancement factor (2 * 10(5)) was quantitatively
      reproducible on both silicon and paper substrates. The silicon substrates gave
      quantitatively reproducible results even after thermal annealing. The paper-based
      SERS substrate was also used to swab and detect probe molecules deposited on a
      solid surface.

PMID- 22653152
TI  - Identification of two novel mutations in SLC29A3 encoding an equilibrative
      nucleoside transporter (hENT3) in two distinct Syrian families with H syndrome:
      expression studies of SLC29A3 (hENT3) in human skin.
AB  - BACKGROUND: H syndrome is a rare autosomal recessive genetic disorder which
      involves the skin and other systemic organs and is caused by mutations in the
      SLC29A3 gene. OBJECTIVES: To disclose the molecular basis of H syndrome in two
      Syrian families, and to determine the localization of hENT3 in human skin.
      METHODS: DNA from two Syrian families with H syndrome was analyzed through direct
      sequencing, and the expression of hENT3 in normal human skin was investigated by
      in situ hybridization and immunostaining. RESULTS: We identified two novel
      mutations in the SLC29A3 gene: a homozygous splice site mutation IVS1+2T>G
      predicted to cause a splicing error, and a homozygous missense mutation c.1157G>A
      (p.R386Q) which substituted highly conserved amino acid residue in a
      transmembrane domain of hENT3. Furthermore, we demonstrate that hENT3 is
      expressed in histiocytes as well as in endothelium of blood and lymphatic vessels
      in normal human skin. CONCLUSIONS: Our results further enhance the mutation
      spectrum of the SLC29A3 gene for this rare genetic disorder, and also suggest
      potential pathomechanisms for the skin lesions resulting from SLC29A3 mutations.

PMID- 22653155
TI  - Characterization of the transcriptome in isolated and transplanted mouse
      pancreatic islets: associations with engraftment and dysfunction.
AB  - The transplantation of pancreatic islets is an option for therapeutic management
      of hypoglycemia unawareness in select patients with type 1 diabetes mellitus.
      Characteristics of the transcriptome of freshly isolated islets, islet
      allografts, and islet isograft are reported in the literature. However, no single
      experiment has undertaken a comparison of the islet allograft to isograft.
      Potential implications of the latter are the use in diagnosis of rejection and to
      discover the molecular pathways in islet allograft dysfunction after transplant.
      Here, the mouse model of islet transplant is used to characterize the
      transcriptome of freshly isolated islets and compare islet graft in an isogeneic
      vs. allogeneic host using an Affymetrix GeneChip(r) Array assay. A set of islet
      associated transcripts (IAT) was developed, and subsequently shown to have high
      level of expression in islet allografts and isografts harvested either five- or
      ten-days after transplant. Furthermore, specific analysis of transcriptome
      differences between islet isografts and pre-rejection allografts (ten-day),
      reveal a series of islet rejection associated transcripts (IRAT). Nearly half of
      IRAT show overlap with previously described pathogenesis based transcript sets
      identified in the setting of mouse kidney allograft rejection. The novel
      transcripts identified to be associated with islet rejection include those
      involved in chemotaxis or lymphocyte function. Although use of biopsy based
      monitoring of humans islet transplants remains difficult at the present time,
      this study provides proof of principle for a transcriptome based technique for
      islet graft rejection monitoring and describes the transcripts associated with
      islet graft dysfunction.

PMID- 22653157
TI  - Ferromagnetic exchange in a twisted, oxime-bridged [Mn(III)2] dimer.
AB  - The dimeric complex [Mn(III)(2)(Naphth-sao)(2)(Naphth-saoH)(2)(MeOH)(2)].4MeOH
      (1.4MeOH), acts as a simple model complex with which to examine the magneto
      structural relationship in polymetallic, oxime-bridged Mn(III) complexes. Dc
      magnetic susceptibility studies reveal that ferromagnetic exchange is mediated
      through the heavily twisted Mn-O-N-Mn moiety (J = +1.24 cm(-1)) with
      magnetisation measurements at low temperatures and high fields suggesting
      significant anisotropy. Simulations of high field, high frequency EPR data reveal
      a single ion anisotropy, D((Mn(III))) = -3.94 cm(-1). Theoretical studies on
      simplified model complexes of 1 reveal that calculated values of the exchange
      coupling and the anisotropy are in excellent agreement with experiment, with the
      weak ferromagnetism resulting from an accidental orthogonality between the Mn-N-O
      plane of the first Mn(III) ion and the Jahn-Teller axis of the second Mn(III)
      ion.

PMID- 22653156
TI  - A cuprous oxide-reduced graphene oxide (Cu2O-rGO) composite photocatalyst for
      hydrogen generation: employing rGO as an electron acceptor to enhance the
      photocatalytic activity and stability of Cu2O.
AB  - Photocorrosion, that causes rapid deactivation of Cu(2)O photocatalysts, was
      addressed by incorporating this oxide in a composite with reduced graphene oxide
      which acts as an electron acceptor to extract photogenerated electrons from
      Cu(2)O. Cu(2)O-rGO composite engineering also allows enhancing significantly
      photocatalytic activities of Cu(2)O for H(2) generation.

PMID- 22653158
TI  - Low-frequency rTMS over right dorsolateral prefrontal cortex in the treatment of
      resistant depression: cognitive improvement is independent from clinical
      response, resting motor threshold is related to clinical response.
AB  - BACKGROUND: Clinical studies have shown that repetitive transcranial magnetic
      stimulation (rTMS) is effective in a certain percentage of treatment-resistant
      depression (TRD). The left dorsolateral prefrontal cortex (DLPFC) 10 Hz rTMS
      stimulation received FDA approval in 2008, although different rTMS protocols have
      also shown their effectiveness in reducing depressive symptoms. We investigated
      the clinical, cognitive and neurophysiologic effects of a 3 weeks' protocol of
      low-frequency rTMS applied over the right DLPFC in resistant depression. METHODS:
      Twenty-eight patients with TRD (age range 28-55) received low-frequency rTMS (1
      Hz) over the right DLPFC in a 3-week open trial. Hamilton scales for depression
      and anxiety, Corsi block-tapping test, phonemic verbal fluency, right and left
      resting motor thresholds were evaluated in each subject over the trial period.
      RESULTS: At the end of the trial 42.9% of the subjects were considered as
      responders. A significant reduction of both HAMD (p < 0.001) and HAMA (p < 0.01)
      total scores was observed. At the 3rd week, the performances in Corsi test (p <
      0.02) and phonemic verbal fluency (p = 0.065) were improved independently from
      depressive symptoms variation. At the end of the rTMS protocol, a significantly
      decreased left hemisphere resting motor threshold was registered (p < 0.01),
      while right hemisphere resting motor threshold did not show significant
      variation. CONCLUSION: Low-frequency rTMS over the right DLPFC appeared effective
      in 42.9% of depressive resistant subjects in this sample. A significant decrease
      in left hemisphere resting motor threshold was observed only in responders, while
      a trend for improvement in cognitive function has been found and appeared
      independent from clinical response.

PMID- 22653159
TI  - Synthesis of polystyrene microspheres and functionalization with Pd(0)
      nanoparticles to perform bioorthogonal organometallic chemistry in living cells.
AB  - We have developed miniaturized heterogeneous Pd(0)-catalysts (Pd(0)-microspheres)
      with the ability to enter cells, stay harmlessly within the cytosol and mediate
      efficient bioorthogonal organometallic chemistries (e.g., allylcarbamate cleavage
      and Suzuki-Miyaura cross-coupling). This approach is a major addition to the
      toolbox available for performing chemical reactions within cells. Here we
      describe a full protocol for the synthesis of the Pd(0)-microspheres from readily
      available starting materials (by the synthesis of size-controlled amino
      functionalized polystyrene microspheres), as well as for their characterization
      (electron microscopy and palladium quantitation) and functional validation ('in
      solution' and 'in cytoplasm' conversions). From the beginning of the synthesis to
      functional evaluation of the catalytic device requires 5 d of work.

PMID- 22653160
TI  - Synthesis of oligo(poly(ethylene glycol) fumarate).
AB  - This protocol describes the synthesis of oligo(poly(ethylene glycol) fumarate)
      (OPF; 1-35 kDa; a polymer useful for tissue engineering applications) by a one
      pot reaction of poly(ethylene glycol) (PEG) and fumaryl chloride. The procedure
      involves three parts: dichloromethane and PEG are first dried; the reaction step
      follows, in which fumaryl chloride and triethylamine are added dropwise to a
      solution of PEG in dichloromethane; and finally, the product solution is filtered
      to remove by-product salt, and the OPF product is twice crystallized, washed and
      dried under vacuum. The reaction is affected by the molecular weight of PEG and
      reactant molar ratio. The OPF product is cross-linked by radical polymerization
      by either a thermally induced or ultraviolet-induced radical initiator, and the
      physical properties of the OPF oligomer and resulting cross-linked hydrogel are
      easily tailored by varying PEG molecular weight. OPF hydrogels are injectable,
      they polymerize in situ and they undergo biodegradation by hydrolysis of ester
      bonds. The expected time required to complete this protocol is 6 d.

PMID- 22653161
TI  - Targeted axon-attached recording with fluorescent patch-clamp pipettes in brain
      slices.
AB  - Understanding the physiology of axons in the central nervous system requires
      experimental access to intact axons. This protocol describes how to perform cell
      attached recordings from narrow axon fibers (phi <1 MUm) in acute and cultured
      brain slice preparations (with a success rate of ~50%). By using fluorophore
      coated glass pipettes and Nipkow disk confocal microscopy, fluorescently labeled
      axons can be visually targeted under online optical control. In the cell-attached
      configuration, axonal action potentials are extracellularly recorded as unit
      like, sharp negative currents. The axon morphology labeling and cell-attached
      recordings of axons can be completed within 1-2 h. The recordings are stable for
      at least 30 min.

PMID- 22653163
TI  - Is the carotid intima-media thickness really a good surrogate marker of
      atherosclerosis?
AB  - AIM: Intima-media thickness (IMT) is considered a surrogate measurement of
      atherosclerosis but this is still under debate. METHODS: To evaluate the
      relationship between carotid IMT and atherosclerosis, postmortem specimens of the
      distal segments of the left common carotid artery (CCA) from 133 Korean men aged
      from 20 to 78 years were used for histopathology and computer-assisted
      morphometry. Blood lipids and atherosclerosis-associated collagen and elastin
      were quantitatively analyzed. RESULTS: Correlation coefficients of IMT were
      smaller than those of intima thickness but IMT was well associated with age (r=
      0.55, p <0.00001), atherosclerosis score (or grade, AS, r= 0.73, p < 0.00001),
      plaque area (PA, r= 0.72, p <0.00001), total cholesterol (TC, r= 0.69, p
      <0.00001), low-density lipoprotein cholesterol (LDL-c, r= 0.72, p <0.00001) and
      triglyceride (TG, r= 0.38, p < 0.001). Coronary artery stenosis (CAS) and
      coronary calcification were also well associated with age (p <0.00001), IMT (p
      <0.005) and PA (p <0.00001). When IMT was thicker than 1 mm, the possibility of
      carotid atherosclerosis accompanied with CAS and coronary calcification, TC, LDL
      c and TG was much higher (CAS with coronary calcification,p <0.005; TC, p
      <0.00001; LDL-c, p < 0.00005; TG, p <0.00001). Collagen tended to increase while
      elastin tended to decrease as AS increased (p <0.005); collagen increased and
      elastin decreased (p <0.00001) when comparing plaque to the plaque-free area in
      the same segment. CONCLUSION: These results support that the carotid IMT in
      association with TC, LDL-c and TG can be used as a good surrogate marker of
      atherosclerosis and predictor of coronary heart disease. Plaque formation may
      influence significant quantitative changes in collagen and elastin.

PMID- 22653162
TI  - Assessment of mitochondrial respiratory chain enzymatic activities on tissues and
      cultured cells.
AB  - The assessment of mitochondrial respiratory chain (RC) enzymatic activities is
      essential for investigating mitochondrial function in several situations,
      including mitochondrial disorders, diabetes, cancer, aging and neurodegeneration,
      as well as for many toxicological assays. Muscle is the most commonly analyzed
      tissue because of its high metabolic rates and accessibility, although other
      tissues and cultured cell lines can be used. We describe a step-by-step protocol
      for a simple and reliable assessment of the RC enzymatic function (complexes I
      IV) for minute quantities of muscle, cultured cells and isolated mitochondria
      from a variety of species and tissues, by using a single-wavelength
      spectrophotometer. An efficient tissue disruption and the choice for each assay
      of specific buffers, substrates, adjuvants and detergents in a narrow
      concentration range allow maximal sensitivity, specificity and linearity of the
      kinetics. This protocol can be completed in 3 h.

PMID- 22653164
TI  - Adiponectin and smoking status: a systematic review.
AB  - AIM: Smoking and adiponectin are individually associated with cardiometabolic
      pathologies. The present systematic review was carried out in order to summarize
      the association between the smoking status and circulating adiponectin levels.
      METHODS: Original articles, restricted to epidemiological studies (by a cross
      sectional, case-control and cohort study design) and intervention studies for
      adult humans, were screened for the years 1995-2010. All of the research group
      members then selected the eligible literature and assessed the articles in a
      structured systematic review manner. RESULTS: There were 11 key studies, which
      included 9 articles with a cross-sectional design and 2 articles with an
      intervention design. Most cross-sectional studies reported lower levels of
      adiponectin in current smokers than in non/never smokers and/or ex-smokers, while
      2 studies reported a non-significant difference in adiponectin between male
      smokers and non-smokers. The two intervention studies, conducted in patients on 9
      week bupropion treatment and 6-month non-pharmacological treatment, reported that
      smoking cessation increased the adiponectin levels. CONCLUSION: This review
      suggests that there is a decreased adiponectin level in current smokers and this
      reduction can be reversed by quitting smoking. More studies are required to
      confirm the findings and elucidate the biological mechanisms underlying the
      association between the smoking status and adiponectin levels.

PMID- 22653165
TI  - Anti-atherosclerotic potential of dihydropyridine calcium channel blockers.
AB  - Dihydropyridine calcium channel blockers (CCBs) are widely used agents for
      patients with hypertension. Dihydropyridine CCBs lower blood pressure mainly
      through vasodilation and reduction of peripheral resistance, and several clinical
      studies have demonstrated that they have clinical benefits in patients with
      cardiovascular diseases. In addition, some studies have indicated that
      dihydropyridine CCBs have anti-atherogenic effects beyond their blood pressure
      lowering effects. In fact, several studies using atherosclerotic model animals
      have revealed that dihydropyridine CCBs suppress atherosclerotic lesion
      formation. It is well known that the production of reactive oxygen species (ROS)
      is involved in the progression of atherosclerosis by stimulating the production
      of inflammatory factors such as chemokines, cytokines and adhesion molecules.
      Dihydropyridine CCBs can suppress ROS generation and subsequent inflammatory
      actions in vascular cells and arterial walls. Furthermore, several reports have
      revealed that dihydropyridine CCBs suppress the expression of adhesion molecules,
      thereby inhibiting monocyte adhesion to endothelial cells, which is thought to be
      an early step in the pathogenesis of atherosclerosis. In smooth muscle cells,
      dihydropyridine CCBs suppress cell proliferation and migration in vitro and in
      vivo. In macrophages, dihydropyridine CCBs decrease cholesterol accumulation and
      intracellular cholesterol esterification, and increase cholesteryl ester
      hydrolysis. Moreover, dihydropyridine CCBs suppress the expression of matrix
      metalloproteinases, which affects the stability of atheromatous plaques.
      Interestingly, recent studies have revealed that the anti-atherosclerotic effects
      of dihydropyridine CCBs are mediated, at least in part, via the activation of
      peroxisome proliferator-activated receptor-gamma. In this review, we focus on the
      anti-atherosclerotic effects of dihydropyridine CCBs beyond their blood pressure
      lowering effects.

PMID- 22653166
TI  - Statistical reassessment of the association between waist circumference and
      clustering metabolic abnormalities in Japanese population.
AB  - AIM: The use of ethnic-specific cutoff values of waist circumference (WC) has
      been recently recommended, but they were originally developed on different
      statistical grounds. We investigated whether different statistical procedures and
      clinical settings generate different WC cutoff values in one ethnic population.
      METHODS: We recruited 3810 Japanese subjects and performed the following three
      statistical analyses: 1) search for WC cutoff points associated with the risk of
      clustering metabolic abnormalities, 2) calculation of WC associated with certain
      body mass index (BMI) levels, 3) evaluation with receiver operating
      characteristic (ROC) curves for the risk. We also simulated population models to
      evaluate whether WC cutoff values depend on the clinical settings of the study
      population. RESULTS: First, in risk analysis, males and females had the same risk
      when females had 10 cm larger WC than males, although the risk increased almost
      linearly, without any clear threshold. Second, WC corresponding to BMI of 25
      kg/m(2) was 87 cm in males and 85 cm in females, with a slight sex difference.
      Third, ROC curves showed that the male optimal cutoff value was 85 cm, larger
      than the female one (79 cm). However, simulated population models with various WC
      distributions gave different ROC curves and different WC cutoff values.
      Furthermore, WC cutoff values varied by age in any of the three statistical
      procedures. CONCLUSIONS: Different statistical grounds could generate different
      WC cutoff values. If one plans to establish a unified trans-ethnic diagnostic
      tool of metabolic syndrome, ethnic-specific WC cutoff values should be primarily
      provided based on a unified statistical ground.

PMID- 22653167
TI  - Blood transfusion practice in critically ill patients: a single institutional
      experience.
AB  - OBJECTIVES: To assess the transfusion practice in the intensive care unit (ICU)
      in a general hospital in Kuwait relative to indications, pretransfusion
      hemoglobin, red blood cell (RBC) use and outcome. SUBJECTS AND METHODS: 475
      patients were admitted to the ICU during the study period (January 2009 to
      February 2010). Ninety-nine received RBC transfusion. Demographic, clinical and
      transfusion data were prospectively collected for the 99 patients who were
      followed up for 30 days, until hospital discharge, or death, whichever occurred
      first. Indications for RBC transfusion included hemorrhage in 39 patients,
      improving oxygen-carrying capacity in 55, and hemolysis in 5. RESULTS: Of the 99
      transfused patients, 22 (22.22%) were also transfused after discharge from the
      ICU. Transfusions were more frequent in patients admitted with respiratory
      failure (30, 30.3%), hemorrhagic shock (24, 24.2%), and septic shock (18, 18.4%).
      The mean pretransfusion hemoglobin in ICU transfusions was statistically
      different (70.9 +/- 12.7 g/l) from transfusions after discharge (79.7 +/- 9.4
      g/l) (p < 0.001). Longer ICU stay was associated with more RBC units transfused
      per transfusion episode per patient (p < 0.001). The Sequential Organ Failure
      Assessment (SOFA) score was significantly associated with the number of RBC units
      transfused per patient (p = 0.006). Mortality was significantly associated with
      Acute Physiology and Chronic Health Evaluation II and SOFA scores, the need and
      duration for mechanical ventilation, and the length of stay in hospital.
      CONCLUSION: Intensivists in our center followed a restrictive transfusion
      practice, by adopting a low pretransfusion hemoglobin threshold. Decisions on RBC
      transfusions seemed in most cases to be based on a 'transfusion trigger' rather
      than a physiologic need.

PMID- 22653168
TI  - Surgical trauma and postoperative immune dysfunction.
AB  - BACKGROUND: In postoperative sepsis, mortality is increased due to the surgically
      induced immune dysfunction. Further causes of this traumatic effect on the immune
      system include burn injuries and polytrauma, as well as endogenous traumata like
      stroke. Several animal models have been defined to analyse the characteristics of
      trauma-induced immune suppression. This article will correlate our results from
      animal studies and clinical observations with the recent literature on
      postoperative immune suppression. METHODS: The previously described model of
      surgically induced immune dysfunction (SID) was performed in mice by laparotomy
      and manipulation of the small intestine in the antegrade direction. Blood samples
      were collected 6 and 72 h following SID to analyse the white blood cell count and
      corticosterone levels. To assess the postoperative immune status in humans, we
      analysed expression of HLA-DR on monocytes of 118 patients by flow cytometry
      prior to and 24, 48 and 72 h after surgery. RESULTS: The postoperative immune
      suppression in our SID model is characterised by lymphocytopenia and
      significantly increased corticosterone levels in mice dependent on the degree of
      surgical trauma. This is comparable to the postoperative situation in humans:
      major and especially long-lasting surgery results in a significantly reduced
      expression of HLA-DR on circulating monocytes. Previous studies describe a
      similar situation following burn injury and endogenous trauma, i.e. stroke.
      CONCLUSIONS: We suggest the completion of our previously published sepsis
      classification due to the immune status at the onset of sepsis: type A as the
      spontaneously acquired sepsis and type B as sepsis in trauma-induced pre-existing
      immune suppression.

PMID- 22653170
TI  - Hypersensitivity reactions to vaccine constituents:  a case series and review of
      the literature.
AB  - Vaccines are composed of immunogens, preservatives, adjuvants, antibiotics, and
      manufacturing by-products. Components of vaccines may rarely elicit adverse
      reactions in susceptible individuals, thus raising concerns regarding vaccine
      safety. In this report, we add to the medical literature 3 cases of cutaneous
      delayed-type hypersensitivity to the vaccine preservative aluminum. We provide a
      review of major constituents in vaccines that have elicited immediate-type or
      delayed-type hypersensitivity reactions and describe their clinical
      manifestations. We include a table of the Food and Drug Administration-approved
      vaccines, which lists the quantities of major components including ovalbumin (egg
      protein), gelatin, aluminum, neomycin, 2-phenoxyethanol, thimerosal, and
      formaldehyde. Our goals were to inform physicians on the variety of
      hypersensitivity reactions to common vaccines and to provide information on the
      choice of vaccines in patients with suspected hypersensitivity.

PMID- 22653171
TI  - The role of contact allergens in chronic idiopathic urticaria.
AB  - OBJECTIVE: The objective of this study was to determine whether contact allergens
      play a role in chronic idiopathic urticaria (CIU). METHODS: We conducted a
      longitudinal prospective study of 23 patients with CIU. Patients were patch
      tested to a modified North American Contact Dermatitis Group standard, fragrance,
      and cosmetic series; other series were tested as warranted by relevant history
      and physical examination. Readings were performed at 48 and 72 hours. Patients
      were counseled to avoid proven contact allergens and were followed up 2 to 9
      months after testing. RESULTS: Twenty-one of 23 patients were female. The mean
      age was 46 years. The mean duration of urticaria was 32 months. Of the 23
      patients, 8 (35%) experienced improvement of their symptoms with allergen
      avoidance. Four (17%) experienced a complete remission, and 4 (17%) experienced
      partial improvement. Two of the complete responders challenged themselves to
      proven contact allergens and developed urticaria, which resolved upon allergen
      avoidance. The most common allergens were potassium dichromate (n = 9), nickel
      sulfate (n = 7), Myroxylon pereirae (n = 6), cobalt chloride, neomycin, p
      phenylenediamine (n = 5); fragrance mix I, fragrance mix II (n = 4); cinnamic
      aldehyde (n = 3); and formaldehyde (n = 2). CONCLUSIONS: Patch testing may be
      helpful in the evaluation of CIU patients for whom previous workup has failed to
      reveal an etiology.

PMID- 22653172
TI  - The Sino-American belt study: nickel and cobalt exposure, epidemiology, and
      clinical considerations.
AB  - BACKGROUND: Nickel and cobalt are common causes of metal allergy. OBJECTIVE: The
      objective of this study was to investigate nickel and cobalt exposure in belt
      buckles by testing 701 belts purchased in China and the United States and to
      consider the prevalence of nickel allergy and its relevance among Chinese
      patients. METHODS: Seven hundred one belt buckles purchased in China and the
      United States were tested for nickel and cobalt release. Six hundred thirty-one
      Chinese patients with suspected allergic contact dermatitis were patch tested and
      interviewed to determine clinical relevance of results. The Chinese and American
      literature was reviewed to investigate trends in nickel prevalence over the past
      decades. RESULTS: Sixty percent (n = 219) of belts purchased in China (n = 365)
      released nickel, and 0.5% (n = 2) released cobalt; 55.7% (n = 187) in the United
      States (n = 336) released nickel, and 0.9% (n = 3) released cobalt. Belt
      dermatitis was a significant clinical finding in 34.8% of Chinese nickel-allergic
      patients. Literature review suggests increasing nickel allergy prevalence in the
      United States and China. CONCLUSIONS: Metallic belt buckles are an important
      source of nickel exposure to consumers. Belts from lowest socioeconomic vendors
      were more likely to release nickel. Belts with silver color and dark metallic
      color were more likely to release nickel and cobalt, respectively. Clinical
      findings show belt dermatitis in China to be a problem.

PMID- 22653173
TI  - Neighborial allergy:  a hidden cause of nonoccupational airborne contact
      dermatitis in a housewife from epoxy resin.

PMID- 22653174
TI  - Allergic contact dermatitis to p-tert butylphenol formaldehyde resin in a
      continuous positive airway pressure strap.

PMID- 22653175
TI  - Allergic contact dermatitis from depilatory wax.

PMID- 22653176
TI  - Scalp "sensitivity" without visible lesions.

PMID- 22653177
TI  - Prevention of airborne propolis-induced allergic contact dermatitis with barrier
      cream.

PMID- 22653178
TI  - Isocyanates.
AB  - Owing to the widespread use of isocyanate-derived products across multiple
      industries, it is important for physicians to be aware of their sensitizing
      potential. We first provide a general overview of isocyanates and the industries
      that may be associated with exposure to these compounds. This is followed by a
      description of the most commonly used isocyanate products in commercial patch
      test preparations. Finally, we discuss appropriate isocyanate patch testing
      methodology and optimal isocyanate patch test concentrations.

PMID- 22653179
TI  - Female wet workers and contact dermatitis: patch test results and sensitization
      in North-East Italy.

PMID- 22653180
TI  - [Antiperspirants for the therapy of focal hyperhidrosis].
AB  - In Europe often no clear distinction is made between deodorant and
      antiperspirant. Particularly in Germany, the labeling "deo" is used for both.
      Only antiperspirants are capable of influencing the activity of eccrine sweat
      glands. In the treatment of focal hyperhidrosis, the use of aluminum chloride
      solutions represents the first choice. The efficacy is well documented in a
      variety of studies. Subjective side effects include pruritus and - less often -
      irritant dermatitis, which can be treated symptomatically and usually does not
      require discontinuation of the treatment. Rare variants of focal hyperhidrosis
      like auriculotemporal syndrome, Ross syndrome and nevus sudoriferus also are
      suitable for treatment with topical aluminum chloride hexahydrate solutions.

PMID- 22653181
TI  - [Pruritic submammary papular lesions].
AB  - Focal, mostly suprabasal acantholyis with development of dyskeratotic
      keratinocytes are typical histological features of Grover's disease. The
      histological distinction between other forms of acantholytic dermatoses is often
      difficult. A combined assessment of the histological findings and the clinical
      symptoms often allows a clear diagnosis. The disease is self-limiting but
      treatment is necessary in some cases due to the sometimes excessive pruritis.

PMID- 22653182
TI  - Participation of surgical residents in operations: challenging a common
      classification.
AB  - BACKGROUND: One important form of surgical training for residents is their
      participation in actual operations, for instance as an assistant or supervised
      surgeon. The aim of this study was to explore what participation in operations
      entails and how it might be described and analyzed. METHODS: A qualitative study
      was undertaken in a major teaching hospital in London. A total of 122 general
      surgical operations were observed. A subsample of 14 laparoscopic
      cholecystectomies involving one or more residents was analyzed in detail. Audio
      and video recordings of eight operations were transcribed and analyzed
      linguistically. RESULTS: The degree of participation of trainees frequently
      shifted as the operation progressed to the next stage. Participation also varied
      within each stage. When trainees operated under supervision, the supervisors
      constantly adjusted their degree of control over the resident's operative
      maneuvers. CONCLUSIONS: Classifications such as "assistant" and "supervised
      surgeon" describing a trainee's overall participation in an operation potentially
      misrepresent the varying involvement of resident and supervisor. Video recordings
      provide a useful alternative for documenting and analyzing actual participation
      in operations.

PMID- 22653183
TI  - Silicon nanocrystal production through non-thermal plasma synthesis: a
      comparative study between silicon tetrachloride and silane precursors.
AB  - Silicon nanocrystals with sizes between 5 and 10 nm have been produced in a non
      thermal plasma reactor using silicon tetrachloride as precursor. We demonstrate
      that high-quality material can be produced with this method and that production
      rates as high as 140 mg h(-1) can be obtained, with a maximum precursor
      utilization rate of roughly 50%. Compared to the case in which particles are
      produced using silane as the main precursor, the gas composition needs to be
      modified and hydrogen needs to be added to the mixture to enable the nucleation
      and growth of the powder. The presence of chlorine in the system leads to the
      production of nanoparticles with a chlorine terminated surface which is
      significantly less robust against oxidation in air compared to the case of a
      hydrogen terminated surface. We also observe that significantly higher power
      input is needed to guarantee the formation of crystalline particles, which is a
      consequence not only of the different gas-phase composition, but also of the
      influence of chlorine on the stability of the crystalline structure.

PMID- 22653184
TI  - Magnetic behaviour of interacting antiferromagnetic nanoparticles.
AB  - Magnetic properties of interacting La(0.2)Ca(0.8)MnO(3) nanoparticles have been
      investigated. The field-induced transition from antiferromagnetic (AFM) to
      ferromagnetic (FM) state in the La(0.2)Ca(0.8)MnO(3) bulk has been observed at
      exceptionally high magnetic fields. For large particles, the field-induced
      transition widens while magnetization progressively decreases. In small particles
      the transition is almost fully suppressed. The thermoremanence and
      isothermoremanence curves constitute fingerprints of irreversible magnetization
      originating from nanoparticle shells. We have ascribed the magnetic behaviour of
      nanoparticles to a core-shell scenario with two main magnetic contributions; one
      attributed to the formation of a collective state formed by FM clusters in
      frustrated coordination at the surfaces of interacting AFM nanoparticles and the
      other associated with inner core behaviour as a two-dimensional diluted
      antiferromagnet.

PMID- 22653187
TI  - Ultrashort-echo time MR imaging of the patella with bicomponent analysis:
      correlation with histopathologic and polarized light microscopic findings.
AB  - PURPOSE: To correlate short and long T2* water fractions, derived from ultrashort
      echo time (TE) magnetic resonance (MR) imaging, with semiquantitative
      histopathologic and polarized light microscopic (PLM) assessment of human
      cadaveric patellae cartilage. MATERIALS AND METHODS: Twenty human cadaveric
      patellae were evaluated by using ultrashort-TE imaging, spin-echo imaging,
      histopathologic analysis, and PLM, with institutional review board approval.
      Short and long T2* water components were evaluated for each patella by using
      bicomponent fitting of ultrashort-TE signal decay. Four to six regions of
      interest (ROIs) within each patella were chosen for correlation between
      ultrashort-TE bicomponent analysis, histopathologic grading (Mankin score), and
      PLM grading (Vaudey score). RESULTS: Ultrashort-TE imaging with bicomponent
      analysis showed two distinct water components with a short T2* and a longer T2*
      in all patellae. ROI analysis showed that the short T2* fraction was correlated
      significantly with the Mankin (rho = 0.66, P < .001) and Vaudey (rho = 0.68, P <
      .001) scores. The Mankin scores were weakly positively correlated with T2 (rho =
      0.28, P = .13) and short T2* (rho = 0.24, P = .14) but were negatively correlated
      with long T2* (rho = -0.55, P < .01). The Vaudey scores were weakly positively
      correlated with T2 (rho = 0.18, P = .16) and short T2* (rho = 0.22, P = .14) but
      were negatively correlated with long T2* (rho = -0.55, P < .01). CONCLUSION:
      Short T2* water fraction derived from ultrashort-TE imaging with bicomponent
      analysis correlates significantly with both the Mankin and Vaudey scores and may
      serve as a biomarker of cartilage degeneration.

PMID- 22653188
TI  - Adenocarcinomas with predominant ground-glass opacity: correlation of morphology
      and molecular biomarkers.
AB  - PURPOSE: To retrospectively identify successive changes in peripheral lung
      adenocarcinoma that feature dominant ground-glass opacity (GGO) at computed
      tomography (CT) and correlate with biomolecular markers. MATERIALS AND METHODS:
      The institutional review board approved this retrospective study, and all 25
      patients provided informed consent. Patients with lung adenocarcinomas smaller
      than 3 cm in diameter in whom tumor growth could be evaluated with CT before
      surgery were included. Two thoracic radiologists evaluated tumor growth by
      analyzing GGO type (pure or mixed) and size increases. Immunohistochemistry of
      the p53 protein and molecular analysis of the epidermal growth factor receptor
      (EGFR) and K-ras genes were performed. The Fisher exact test was used to assess
      statistical significance. RESULTS: Tumor size increased in 19 of 25 patients
      (76%) during the observation period. The CT changes in 19 patients were
      classified into four patterns: persistent pure GGO (n = 8), change from pure to
      mixed GGO (n = 3), mixed GGO with growth of solid component (n = 4), and mixed
      GGO with growth of GGO component (n = 4). The remaining six patients (24%) had
      pure GGO without any interval changes. Staining for p53 was negative in all 14
      patients with pure GGO and positive in six of 11 patients (55%) with mixed GGO (P
      < .01). In these six patients appearance or growth of the solid component was
      seen. EGFR mutations were found in both pure (36%) and mixed (45%) GGO lesions (P
      = .70). CONCLUSION: Lung adenocarcinomas with a dominant GGO often possess EGFR
      mutations. Interval changes in the solid component may be related to p53
      inactivation.

PMID- 22653189
TI  - Pulmonary lesion assessment: comparison of whole-body hybrid MR/PET and PET/CT
      imaging--pilot study.
AB  - PURPOSE: To compare the performance of magnetic resonance (MR)/positron emission
      tomography (PET) imaging in the staging of lung cancer with that of PET/computed
      tomography (CT) as the reference standard and to compare the quantification
      accuracy of a new whole-body MR/PET system with corresponding PET/CT data sets.
      MATERIALS AND METHODS: Institutional review board approval and informed consent
      were obtained. Ten patients in whom bronchial carcinoma was proven or clinically
      suspected underwent clinically indicated fluorine 18 fluorodeoxyglucose (FDG)
      PET/CT and, immediately thereafter, whole-body MR/PET imaging with a new hybrid
      whole-body system (3.0-T MR imager with integrated PET system). Attenuation
      correction of MR/PET images was segmentation based with fat-water separation.
      Tumor-to-liver ratios were calculated and compared between PET/CT and MR/PET
      imaging. Tumor staging on the basis of the PET/CT and MR/PET studies was
      performed by two readers. Spearman rank correlation was used for comparison of
      data. RESULTS: MR/PET imaging provided diagnostic image quality in all patients,
      with good tumor delineation. Most lesions (nine of 10) showed pronounced FDG
      uptake. One lesion was morphologically suspicious for malignancy at CT and MR
      imaging but showed no FDG uptake. MR/PET imaging had higher mean tumor-to-liver
      ratios than did PET/CT (4.4 +/- 2.0 [standard deviation] for PET/CT vs 8.0 +/-
      3.9 for MR/PET imaging). Significant correlation regarding the tumor-to-liver
      ratio was found between both imaging units (rho = 0.93; P < .001). Identical TNM
      scores based on MR/PET and PET/CT data were found in seven of 10 patients.
      Differences in T and/or N staging occurred mainly owing to modality-inherent
      differences in lesion size measurement. CONCLUSION: MR/PET imaging of the lung is
      feasible and provides diagnostic image quality in the assessment of pulmonary
      masses. Similar lesion characterization and tumor stage were found in comparing
      PET/CT and MR/PET images in most patients.

PMID- 22653190
TI  - How useful is the alpha angle for discriminating between symptomatic patients
      with cam-type femoroacetabular impingement and asymptomatic volunteers?
AB  - PURPOSE: To compare the alpha-angle measurements in volunteers and patients with
      femoroacetabular impingement (FAI) and to develop potential threshold values.
      MATERIALS AND METHODS: This study was approved by the institutional review board;
      all individuals signed informed consent. Magnetic resonance (MR) images at 1.5 T
      in 106 individuals (ages 20-50 years) were analyzed in 53 patients (33 cam- and
      20 mixed-type FAI) and 53 age- and sex-matched asymptomatic volunteers. Alpha
      angles were measured on radially reformatted MR images of the proximal femur by
      two independent readers. Intraclass correlation coefficient (ICC) and receiver
      operating characteristic (ROC) were calculated. RESULTS: Mean alpha angles were
      highest in the anterosuperior segment: 65.4 degrees  +/- 11.5 [standard
      deviation] and 65.2 degrees  +/- 7.3 for readers 1 and 2 in patients and 53.3
      degrees  +/- 9.6 and 55.0 degrees  +/- 8.8 in volunteers, respectively (P < .001,
      patients vs volunteers). Alpha angles greater than 55 degrees  were measured in
      20 (38%) and 33 (62%) of 53 volunteers for readers 1 and 2, respectively. Maximal
      alpha angle in any segment was substantially different (P < .001) in patients and
      volunteers (70.3 degrees  +/- 11.2 vs 57.9 degrees  +/- 10.5 for reader 1; 69.4
      degrees  +/- 8.8 vs 58.7 degrees  +/- 8.9 for reader 2), with a large overlap.
      Overall interobserver agreement was good (ICC, 0.712). ROC showed the largest
      area under the curve at the anterosuperior segment: 0.791 and 0.824 for readers 1
      and 2, respectively (P < .001). A 55 degrees  alpha-angle threshold value gave a
      sensitivity and specificity of 81% and 65% for reader 1 and of 90% and 47% for
      reader 2, respectively. A 60 degrees  alpha-angle threshold value gave a
      sensitivity and specificity of 72% and 76% for reader 1 and 80% and 73% for
      reader 2, respectively. CONCLUSION: There is substantial overlap in the alpha
      angle measurements between volunteers and patients with cam-type deformities.
      Discrimination is best at the anterosuperior segment. Increasing the alpha-angle
      threshold value from 55 degrees  to 60 degrees  reduces false-positive results
      while maintaining a reasonable sensitivity.

PMID- 22653200
TI  - Revitalizing psychiatric drug discovery.
AB  - Psychiatric drug discovery needs to close the systems neuroscience gap to improve
      the clinical success rates of candidate drugs with novel mechanisms of action.

PMID- 22653201
TI  - The gout pipeline crystallizes.

PMID- 22653191
TI  - Factors associated with meniscal extrusion in knees with or at risk for
      osteoarthritis: the Multicenter Osteoarthritis study.
AB  - PURPOSE: To assess the associations of meniscal tears, knee mal-alignment,
      cartilage damage, knee effusion, and body mass index with meniscal extrusion.
      MATERIALS AND METHODS: The Multicenter Osteoarthritis study is an observational
      study of individuals who have or are at risk for knee osteoarthritis (OA). The
      HIPAA-compliant protocol was approved by the institutional review boards of all
      participating centers, and written informed consent was obtained from all
      patients. All subjects with available baseline knee radiographs and magnetic
      resonance (MR) images were included. MR imaging assessment of meniscal
      morphologic characteristics, meniscal position, and cartilage morphologic
      characteristics with use of the Whole-Organ Magnetic Resonance Imaging Score
      system was performed by two musculoskeletal radiologists. Cross-sectional
      associations of severity of meniscal tears, knee malalignment, tibiofemoral
      cartilage damage, knee effusion, and body mass index with meniscal extrusion were
      assessed by using logistic regression, with multiadjustments when testing each
      predictor. RESULTS: A total of 1527 subjects (2131 knees; 2116 medial and 2106
      lateral menisci) were included. Medially, meniscal tears, varus malalignment, and
      cartilage damage were associated with meniscal extrusion, with odds ratios (ORs)
      of 6.3 (95% confidence interval [CI]: 5.0, 8.0), 1.3 (95% CI: 1.1, 1.7), and 1.8
      (95% CI: 1.4, 2.2), respectively. Laterally, meniscal tears, valgus malalignment,
      and cartilage damage were associated with meniscal extrusion, with ORs of 10.3
      (95% CI: 7.1, 14.9), 2.2 (95% CI: 1.5, 3.2), and 2.0 (95% CI: 1.3, 2.9),
      respectively. CONCLUSION: Meniscal tears are not the only factors associated with
      meniscal extrusion; other factors include knee malalignment and cartilage damage.
      Meniscal extrusion is probably an effect of the complex interactions among joint
      tissues and mechanical stresses involved in the OA process.

PMID- 22653202
TI  - Can next-generation antibodies offset biosimilar competition?

PMID- 22653205
TI  - Deal watch: Shire increases focus on regenerative medicine.

PMID- 22653204
TI  - Deal watch: Amgen builds secondary hyperparathyroidism [corrected] pipeline.

PMID- 22653206
TI  - Chemical structure does not define obviousness.

PMID- 22653207
TI  - An audience with... Gregory Lip. Interview by Asher Mullard.

PMID- 22653208
TI  - Outlook for the next 5 years in drug innovation.

PMID- 22653209
TI  - Vismodegib.

PMID- 22653210
TI  - Gene therapy: Crossing mitochondrial barriers.

PMID- 22653211
TI  - Neurodevelopmental disorders: Glutamate blockers show benefit in models of autism
      spectrum disorders.

PMID- 22653219
TI  - The magnetoelectric effect due to local noncentrosymmetry.
AB  - Magnetoelectrics often possess ions located in noncentrosymmetric surroundings.
      Based on this fact we suggest a microscopic model of magnetoelectric interaction
      and show that the spin-orbit coupling leads to spin-dependent electric dipole
      moments of the electron orbitals of these ions, which results in non-vanishing
      polarization for certain spin configurations. The approach accounts for the
      macroscopic symmetry of the unit cell and is valid for both commensurate and
      complex incommensurate magnetic structures. The model is illustrated by the
      examples of MnWO(4), MnPS(3) and LiNiPO(4). Application to other magnetoelectrics
      is discussed.

PMID- 22653218
TI  - Generation, characterization and structural data of chymase binding proteins
      based on the human Fyn kinase SH3 domain.
AB  - The serine protease chymase (EC = 3.4.21.39) is expressed in the secretory
      granules of mast cells, which are important in allergic reactions. Fynomers,
      which are binding proteins derived from the Fyn SH3 domain, were generated
      against human chymase to produce binding partners to facilitate crystallization,
      structure determination and structure-based drug discovery, and to provide
      inhibitors of chymase for therapeutic applications. The best Fynomer was found to
      bind chymase with a KD of 0.9 nM and koff of 6.6x10 (-4)  s (-1) , and to
      selectively inhibit chymase activity with an IC 50 value of 2 nM. Three different
      Fynomers were co-crystallized with chymase in 6 different crystal forms overall,
      with diffraction quality in the range of 2.25 to 1.4 A resolution, which is
      suitable for drug design efforts. The X-ray structures show that all Fynomers
      bind to the active site of chymase. The conserved residues Arg15-Trp16-Thr17 in
      the RT-loop of the chymase binding Fynomers provide a tight interaction, with
      Trp16 pointing deep into the S1 pocket of chymase. These results confirm the
      suitability of Fynomers as research tools to facilitate protein crystallization,
      as well as for the development of assays to investigate the biological mechanism
      of targets. Finally, their highly specific inhibitory activity and favorable
      molecular properties support the use of Fynomers as potential therapeutic agents.

PMID- 22653220
TI  - The change in low-density lipoprotein cholesterol concentration is positively
      related to plasma docosahexaenoic acid but not eicosapentaenoic acid.
AB  - AIM: The Japan EPA Lipid Intervention Study (JELIS) reported a 19% reduction of
      the risk for coronary artery disease after long-term use of pure eicosapentaenoic
      acid (EPA) in Japanese patients with hypercholesterolemia. The variation in
      plasma fatty acid composition influenced the risk of coronary events. The aim of
      this study was to examine in JELIS participants the possible correlation of
      changes in plasma fatty acids with those of serum lipids. METHODS: The
      coefficient for the correlation between the absolute change in plasma fatty acid
      concentrations and the changes in serum lipids was calculated in 13,901 JELIS
      participants. RESULTS: Low-density lipoprotein (LDL) cholesterol exhibited a
      positive correlation with docosahexaenoic acid (DHA; r=0.117 in control group,
      r=0.155 in EPA group) and linoleic acid (r=0.139 in control group, r=0.177 in EPA
      group), but the correlation coefficients with EPA (r=0.097 in control group, r=
      0.032 in EPA group) were less than 0.1. We distributed the patients into 9 groups
      according to tertiles of the change in EPA and DHA. The average absolute decrease
      of LDL cholesterol and L/H ratio in each group was significantly smaller
      (p<0.001) in the DHA-high tertile, but not in any EPA tertile. CONCLUSION: The
      changes in DHA, but not in EPA, showed a positive correlation with the changes in
      LDL-cholesterol.

PMID- 22653221
TI  - Ability of emergency physicians to detect early ischemic changes of acute
      ischemic stroke on cranial computed tomography.
AB  - OBJECTIVE: The objective of this study was to evaluate the ability of emergency
      physicians (EPs) to diagnose early ischemic changes due acute ischemic stroke on
      cranial computed tomography (CT). SUBJECTS AND METHODS: Three EPs interpreted CT
      scans obtained within 3 h of symptom onset in 50 patients with acute stroke. The
      CT scans were interpreted by the EPs and compared to official neuroradiologist
      reports as a gold standard. K statistics were calculated to determine agreement
      among the three readers. Sensitivities and specificities were analyzed for each
      reader. RESULTS: The EPs' sensitivities were 50, 45.5, and 45.5%, and
      specificities were 64.3, 82.1, and 64.3%, respectively. Focal parenchymal
      hypodensity was the criterion for which the EPs were the most sensitive (77.3%).
      The ability of EPs to recognize early ischemic changes on CT scans in acute
      ischemic stroke was moderate based on sensitivities. CONCLUSION: Based on this
      study, EPs must be trained especially for recognizing early ischemic changes in
      acute ischemic stroke to improve their accuracy of interpretation.

PMID- 22653222
TI  - Functional microspheres of graphene quantum dots.
AB  - Graphene-quantum-dot microspheres (GQDSs) have been prepared by assembly of
      graphene quantum dots (GQDs) via a water-in-oil (W/O) emulsion technique without
      the addition of any surfactants. Although made of quantum-sized graphene dots,
      the as-formed GQDSs are solid and remain intact after slight ultrasonication. The
      versatile W/O emulsion method allows the in situ intercalation of functional
      nanocomponents into the GQDSs for specific applications. As exemplified by the
      Fe(3)O(4)-containing GQDSs, Fe(3)O(4)-GQDSs exhibit a large magnetic response.
      Furthermore, the embedded Fe(3)O(4) nanoparticles in GQDSs can act as the
      catalysts for the growth of carbon nanotubes (CNTs), which opens the
      opportunities for fabricating new complex structures of CNTs surrounding GQDSs by
      simple chemical vapor deposition.

PMID- 22653216
TI  - Are sirtuins viable targets for improving healthspan and lifespan?
AB  - Although the increased lifespan of our populations illustrates the success of
      modern medicine, the risk of developing many diseases increases exponentially
      with old age. Caloric restriction is known to retard ageing and delay functional
      decline as well as the onset of disease in most organisms. Studies have
      implicated the sirtuins (SIRT1-SIRT7) as mediators of key effects of caloric
      restriction during ageing. Two unrelated molecules that have been shown to
      increase SIRT1 activity in some settings, resveratrol and SRT1720, are excellent
      protectors against metabolic stress in mammals, making SIRT1 a potentially
      appealing target for therapeutic interventions. This Review covers the current
      status and controversies surrounding the potential of sirtuins as novel
      pharmacological targets, with a focus on SIRT1.

PMID- 22653217
TI  - Strategies for the discovery and development of therapies for metastatic breast
      cancer.
AB  - Nearly all deaths caused by solid cancers occur as a result of metastasis--the
      formation of secondary tumours in distant organs such as the lungs, liver, brain
      and bone. A major obstruction to the development of drugs with anti-metastatic
      efficacy is our fragmented understanding of how tumours 'evolve' and metastasize,
      at both the biological and genetic levels. Furthermore, although there is
      significant overlap in the metastatic process among different types of cancer,
      there are also marked differences in the propensity to metastasize, the extent of
      metastasis, the sites to which the tumour metastasizes, the kinetics of the
      process and the mechanisms involved. Here, we consider the case of breast cancer,
      which has some marked distinguishing features compared with other types of
      cancer. Considerable progress has been made in the development of preclinical
      models and in the identification of relevant signalling pathways and genetic
      regulators of metastatic breast cancer, and we discuss how these might facilitate
      the development of novel targeted anti-metastatic drugs.

PMID- 22653225
TI  - Superior laryngeal nerve loop: patterns and surgical implications.
AB  - This study clarifies the patterns of the superior laryngeal nerve loop (SLN
      loop), connecting the cervical sympathetic chain (CSC) and the SLN and its
      branches, so as to provide an anatomic basis for decreasing the risk of injury to
      the external laryngeal nerve (ELN) during neck surgery. Fifty Chinese adult human
      cadavers fixed with 4 % formalin were dissected, and their SLN loop patterns were
      analyzed and summarized. In 98 of 100 sides the CSC anastomosed with the SLN and
      its branches, forming a looped nerve structure which we called the SLN loop. The
      SLN loops could be divided into five types: e ( n ), t ( n ), i ( n ), t ( n ) e
      ( n ), and i ( n ) e ( n ) based on morphological variations. The results
      demonstrated that e ( n ) was most frequently found in the samples (82/100)
      followed by t ( n ) (9/100), i ( n ) (3/100), t ( n ) e ( n ) (2/100), and i ( n
      ) e ( n ) (2/100). Comparing with the previous work, we identified additional 18
      subtypes of the SLN loop. The relations of the SLN loop to the surrounding
      structures were complicated, which brought more challenges to thyroidectomy.
      Thus, we do not advocate routine identification of ELN/ELN loop during the
      process of thyroidectomy, especially systematic identification of ELN during
      operation. However, this study introduces the possibility that nerve injury can
      be avoided by exposure of the nerve via careful dissection in the region of the
      superior pole of the thyroid gland to the extent that we can initiate individual
      ligation of the superior polar vessels, along with the help of neuromonitors,
      video monitors, and magnifying loupes.

PMID- 22653226
TI  - Interventions using high-technology communication devices: a state of the art
      review.
AB  - BACKGROUND/AIMS: In the last 20 years the range of high-technology augmentative
      and alternative communication (AAC) aids has rapidly expanded. This review aimed
      to provide a 'state of the art' synthesis, to provide evidence-based information
      for researchers, potential users and service providers. METHODS: Electronic
      databases were searched from 2000 to 2010, together with reference lists of
      included papers and review papers. The review considered work of any design which
      reported an intervention using high-tech AAC with people who have communication
      difficulties (excluding those with solely hearing or visual loss) published in
      peer-reviewed journals. RESULTS: Sixty-five papers reporting interventions using
      high-tech AAC were identified. There was evidence that high-technology AAC may be
      beneficial across a range of diagnoses and ages. The evidence, however, is
      currently drawn from studies using designs considered to be at high risk of bias.
      CONCLUSION: The review suggests that the high level of individual variation in
      outcome requires a greater understanding of characteristics of clients who may or
      may not benefit from this technology. Also, the wide range of outcomes measured
      requires further work in the field to establish what a 'good outcome' from
      intervention may be.

PMID- 22653228
TI  - Antigen presentation: Visualizing DC dynamics in the lung.

PMID- 22653227
TI  - Graphene: a versatile nanoplatform for biomedical applications.
AB  - Graphene, with its excellent physical, chemical, and mechanical properties, holds
      tremendous potential for a wide variety of biomedical applications. As research
      on graphene-based nanomaterials is still at a nascent stage due to the short time
      span since its initial report in 2004, a focused review on this topic is timely
      and necessary. In this feature review, we first summarize the results from
      toxicity studies of graphene and its derivatives. Although literature reports
      have mixed findings, we emphasize that the key question is not how toxic graphene
      itself is, but how to modify and functionalize it and its derivatives so that
      they do not exhibit acute/chronic toxicity, can be cleared from the body over
      time, and thereby can be best used for biomedical applications. We then discuss
      in detail the exploration of graphene-based nanomaterials for tissue engineering,
      molecular imaging, and drug/gene delivery applications. The future of graphene
      based nanomaterials in biomedicine looks brighter than ever, and it is expected
      that they will find a wide range of biomedical applications with future research
      effort and interdisciplinary collaboration.

PMID- 22653229
TI  - Innate immunity: Destructive interference of PRRs.

PMID- 22653241
TI  - Medical education: eternal values.

PMID- 22653243
TI  - Homocysteine levels and MTHFR polymorphisms in young patients with acute
      myocardial infarction: a case control study.
AB  - INTRODUCTION: Increased levels of homocysteine are known to be associated with
      coronary artery disease (CAD). The most common form of genetic
      hyperhomocysteinemia results from MTHFR polymorphisms. To examine the role of
      homocysteine levels and MTHFR polymorphisms in premature CAD and acute myocardial
      infarction (MI) in the Cypriot population, a case control study was performed in
      Nicosia General Hospital. METHODS: Sixty-three male patients less than 50 years
      old who presented with MI in Nicosia General Hospital were compared with 54
      controls without CAD. Fasting homocysteine and lipids were tested within 24 hrs
      from admission, while MTHFR C677T and A1298C polymorphisms were also tested.
      RESULTS: Mean homocysteine levels were 14.5 mol/L in patients and 12.3 mol/L in
      controls (p=0.017). Mutant homozygous MTHFR C677T was present in 17.7% of the
      patients and 19.2% of the controls (p=0.838), while mutant homozygous MTHFR
      A1298C was found in 16.1% of patients and 13.5% of controls (p=0.690). Mean
      homocysteine levels were 12.6 mol/L in patients with single-vessel CAD and 15.5
      mol/L in patients with multi-vessel CAD (p=0.025). Lower HDL appeared to be
      associated with higher levels of homocysteine with an odds ratio of 0.901,
      indicating that for each unit increase in HDL, the expected odds of having high
      homocysteine levels decreased by approximately 10%. CONCLUSIONS: Higher levels of
      homocysteine are associated with acute MI and multi-vessel disease in Cypriot
      patients under the age of 50. The existence and extent of disease are not
      associated with MTHFR polymorphisms. Lower HDL is associated with higher levels
      of homocysteine.

PMID- 22653242
TI  - Conflict of interest policies and disclosure requirements among European Society
      of Cardiology national cardiovascular journals.
AB  - Disclosure of potential conflicts of interest (COI) is used by biomedical
      journals to guarantee the credibility and transparency of the scientific process.
      COI disclosure, however, is not systematically nor consistently dealt with by
      journals. Recent joint editorial efforts paved the way towards the implementation
      of uniform vehicles for COI disclosure. This paper provides a comprehensive
      editorial perspective on classical COI-related issues. New insights into current
      COI policies and practices among European Society of Cardiology national
      cardiovascular journals, as derived from a cross-sectional survey using a
      standardised questionnaire, are discussed.

PMID- 22653244
TI  - Combined intravenous treatment with ascorbic acid and desferrioxamine to reduce
      myocardial reperfusion injury in an experimental model resembling the clinical
      setting of primary PCI.
AB  - INTRODUCTION: During reperfusion of ischemic myocardium, oxygen-derived free
      radicals are produced and can cause deleterious effects, known as reperfusion
      injury. We aimed to determine if a combination of the antioxidant ascorbic acid
      and an iron-chelating agent desferrioxamine, which reduces the production of the
      hydroxyl radical via ferrum-catalyzed reactions, can exert a protective action
      against reperfusion injury. METHODS: Twenty-two young male farm pigs were
      anesthetized and subjected to 45 mins of ischemia and 3 and a half hours of
      reperfusion, in the left circumflex coronary artery territory, via the inflation
      and deflation of an angioplasty balloon. Animals were randomly assigned to
      receive either an intravenous infusion of 100 mg/ kg ascorbic acid and 60 mg/kg
      desferrioxamine (treatment group, TG) or an equal amount of normal saline
      (control group, CG). The I/R ratio, the ratio of the infarcted (necrotic) zone
      (I) to the myocardial area at risk (R) after 3 and a half hours of reperfusion,
      was calculated using the tetrazolium staining method. Left ventricular end
      diastolic pressure (LVEDP), number of episodes of ventricular arrhythmias, TIMI
      flow in the reperfused vessel, and left ventricular ejection fraction (LVEF) were
      evaluated within the first hour post reperfusion in order to assess further
      injury severity. RESULTS: There was no significant difference in the I/R between
      the TG (27.9 +/- 2.2%) and the CG (32.9 +/- 2.4%) (p=0.15). In both groups there
      was a significant reduction in LVEF (-11.6 +/- 2.28% for TG and -12.0 +/- 2.27%
      for CG, p<0.01 for both groups) and a significant increase in LVEDP (+3.2 +/- 0.9
      mmHg for TG and +4.6 +/- 0.9 mmHg for CG, p<0.01 for both groups) compared to the
      baseline values. No significant difference was noted between groups (p=0.61 for
      LVEF and p=0.60 for LVEDP values, at one hour post reperfusion). In all other
      parameters measured, no significant difference was observed between the study
      groups. CONCLUSIONS: Intravenous treatment with a combination of the antioxidant
      ascorbic acid and the iron-chelating agent desferrioxamine does not provide
      significant protection against myocardial reperfusion injury.

PMID- 22653245
TI  - A propensity score-based comparison of flat panel digital detector fluoroscopy
      versus digital cinefluoroscopy for coronary artery calcium detection.
AB  - INTRODUCTION: Detection of coronary artery calcification (CAC) allows for a
      refined prediction of cardiovascular risk beyond global risk assessment
      algorithms. Newer-generation, high-resolution, flat-panel digital detector (FPDD)
      fluoroscopic systems may provide higher CAC detection rates compared with older
      fluoroscopic devices. METHODS: We compared the CAC detection rates of two
      fluoroscopic techniques in two different cohorts of asymptomatic individuals,
      analyzed within a two-decade time interval. RESULTS: FPDD detected CAC more
      frequently than the older fluoroscopy device, in the more recent and the older
      patient cohort of individuals, respectively. After propensity score matching to
      account for differences in age and risk factor prevalence, the adjusted rates of
      CAC detection remained higher in favor of FPDD (37.7% vs. 23.7%, p=0.026).
      CONCLUSIONS: The ability of newer cine-fluoroscopic systems to identify CAC in a
      larger number of asymptomatic, intermediate-risk individuals may have
      implications for further risk stratification, management of risk factors and long
      term prognosis.

PMID- 22653246
TI  - Surgical treatment for atrial fibrillation: where do we stand?

PMID- 22653247
TI  - Ventricular arrhythmias: from the electrophysiology laboratory to clinical
      practice. Part II: potentially malignant and benign ventricular arrhythmias.

PMID- 22653248
TI  - Understanding mitral valve pathology: three-dimensional transesophageal
      echocardiography parametric maps.

PMID- 22653249
TI  - Catheter-based renal sympathetic denervation for the treatment of resistant
      hypertension: first experience in Greece with significant ambulatory blood
      pressure reduction.
AB  - We describe the first two cases in Greece of catheter-based renal sympathetic
      denervation (RSD) by means of radiofrequency ablation. The procedure was
      performed on middle-aged men with long-standing resistant hypertension (office
      blood pressure, BP 195/115 mmHg and ambulatory BP 190/110 mmHg; office BP 170/95
      mmHg and ambulatory BP 151/87 mmHg) under optimal medical therapy. The
      percutaneous RSD was completed successfully, and led to a significant reduction
      in both office and ambulatory BP at 3 weeks, with no vascular complications,
      while renal function remained unaltered. These cases of RSD suggest that renal
      nerve ablation for the treatment of resistant hypertension constitutes an
      effective and safe therapeutic modality, accompanied by significant reduction of
      ambulatory BP, and broadening of its clinical use in our country is of clinical
      importance.

PMID- 22653250
TI  - Severe mitral regurgitation coexisting with descending thoracic aorta aneurysm:
      staged approach using endovascular repair.
AB  - We describe the case of a 67-year-old man who was referred for the management of
      severe mitral valve regurgitation and coronary artery disease. Further workup
      revealed a descending thoracic aorta aneurysm. He underwent mitral valve
      replacement with coronary artery bypass surgery and, at a second stage,
      endovascular stent graft repair of the descending thoracic aorta aneurysm.

PMID- 22653251
TI  - Successful vaginal delivery in a woman with tetralogy of Fallot and pulmonary
      atresia after four cardiac operations.
AB  - We describe a woman with tetralogy of Fallot and pulmonary atresia, with a
      history of four previous cardiac operations, who decided to bear her own
      children. Under interdisciplinary counselling and the appropriate medical care,
      she underwent a successful vaginal delivery and had a healthy baby.

PMID- 22653252
TI  - What is the place of percutaneous coronary intervention in the management of
      stable angina?

PMID- 22653253
TI  - Pre-participation screening of athletes in Greece: what are the data?

PMID- 22653254
TI  - The HellenicSCORE: a simple tool for measuring cardiovascular disease risk.

PMID- 22653255
TI  - Comparative effects of low-carbohydrate high-protein versus low-fat diets on the
      kidney.
AB  - BACKGROUND AND OBJECTIVES: Concerns exist about deleterious renal effects of low
      carbohydrate high-protein weight loss diets. This issue was addressed in a
      secondary analysis of a parallel randomized, controlled long-term trial. DESIGN,
      SETTING, PARTICIPANTS, AND MEASUREMENTS: Between 2003 and 2007, 307 obese adults
      without serious medical illnesses at three United States academic centers were
      randomly assigned to a low-carbohydrate high-protein or a low-fat weight-loss
      diet for 24 months. Main outcomes included renal filtration (GFR) indices (serum
      creatinine, cystatin C, creatinine clearance); 24-hour urinary volume; albumin;
      calcium excretion; and serum solutes at 3, 12, and 24 months. RESULTS: Compared
      with the low-fat diet, low-carbohydrate high-protein consumption was associated
      with minor reductions in serum creatinine (relative difference, -4.2%) and
      cystatin C (-8.4%) at 3 months and relative increases in creatinine clearance at
      3 (15.8 ml/min) and 12 (20.8 ml/min) months; serum urea at 3 (14.4%), 12 (9.0%),
      and 24 (8.2%) months; and 24-hour urinary volume at 12 (438 ml) and 24 (268 ml)
      months. Urinary calcium excretion increased at 3 (36.1%) and 12 (35.7%) months
      without changes in bone density or clinical presentations of new kidney stones.
      CONCLUSIONS: In healthy obese individuals, a low-carbohydrate high-protein weight
      loss diet over 2 years was not associated with noticeably harmful effects on GFR,
      albuminuria, or fluid and electrolyte balance compared with a low-fat diet.
      Further follow-up is needed to determine even longer-term effects on kidney
      function.

PMID- 22653256
TI  - Differential outcomes of expanded-criteria donor renal allografts according to
      recipient age.
AB  - BACKGROUND AND OBJECTIVES: Expanded-criteria donor (ECD) kidneys are used to
      expand the number of deceased-donor kidney transplants, often for elderly
      recipients. This study sought to determine whether older recipients had
      significantly worse outcomes from receiving ECD kidneys and whether outcomes of
      ECD versus standard-criteria donor (SCD) kidneys differed in younger recipients.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a single-center,
      retrospective review of all primary deceased-donor kidney transplantations
      performed between 2000 and 2005. Group 1 consisted of patients >=60 years of age
      (n=189) who received an ECD (n=96) or an SCD (n=93) kidney. Group 2 consisted of
      patients 40-59 years of age (n=370) who received an ECD (n=105) or an SCD (n=265)
      kidney. RESULTS: Older recipients (group 1) who received ECD kidneys demonstrated
      significantly shortened 5-year actuarial patient and graft survival rates
      compared with older recipients of SCD allografts. Group 1 ECD recipients also had
      significantly worse outcomes than younger (group 2) ECD recipients. In
      multivariate analysis, ECD kidneys remained an independent predictor of poorer
      outcome in group 1. CONCLUSIONS: Morbidity and mortality were increased in
      elderly recipients of ECD kidneys. These findings may have implications in kidney
      allocation policy developments that encourage placement of ECD kidneys for older
      recipients.

PMID- 22653257
TI  - Fallopian tube reanastomosis by laparotomy versus laparoscopy: a meta-analysis.
AB  - OBJECTIVE: To compare efficacy of sterilization reversals by laparotomy versus
      laparoscopy. DESIGN: Meta-analysis. SEARCH STRATEGY: Electronic searches were
      carried out for randomized controlled trials and retrospective and prospective
      clinical studies. Search engines such as PubMed, Science Direct, Medline and the
      Cochrane database were made use of. Our restrictions were English human studies
      published from 1989 to January 2010. INTERVENTIONS: Microsurgical tubal
      reanastomosis performed comparing laparoscopy with laparotomy using a
      microsurgical technique. OUTCOME MEASURES: Primary: overall pregnancy rates,
      including positive clinical pregnancy, intrauterine and ectopic pregnancy rates.
      Secondary: surgery time. RESULTS: Three retrospective comparative studies were
      retrieved from international data that investigated laparotomy versus
      laparoscopy. A total number of 184 patients were included, 88 and 96 respectively
      undergoing laparoscopy and laparotomy. Pregnancy rates achieved by laparoscopy
      ranged from 65 to 80.5% (mean 74.43%) and by laparotomy from 70 to 80% (mean
      71.33%). A subanalysis of two of the three comparative studies show that
      laparoscopy reversal surgery requires a statistically significant longer
      operative time than does laparotomy (p < 0.00001). CONCLUSIONS: There is no
      difference between the laparoscopy and laparotomy approach to tubal reanastomosis
      when regarding overall pregnancy rates, intrauterine and ectopic pregnancy rates.

PMID- 22653258
TI  - [Myasthenia gravis and thymolipoma: a rare variation of a well-known theme].

PMID- 22653259
TI  - Oxidized low-density lipoprotein antigen transport induces autoimmunity in the
      renal tubulointerstitium.
AB  - BACKGROUND/AIMS: Chronic kidney disease involves inflammation/oxidative stress,
      which contributes to progressive kidney injury. METHODS: Male Sprague-Dawley rats
      underwent 5/6 nephrectomy (Nx) or sham Nx and were sacrificed after 2 days, 2
      weeks and 4 weeks. Microarray analysis expression sets over time suggested the
      evolution of renal lymphocyte infiltration and antigen-presenting cell (APC)
      activation after 5/6Nx. RT-PCR analysis also confirmed the migration and
      activation of lymphocytes and APCs through the upregulation of CD3, CXCR3/CXCL10
      and CCR7/CCL19 mRNA in remnant kidney (RK). Purified T lymphocytes from spleen
      and unilateral ureteral obstruction (UUO) kidney were incubated with oxidized low
      density lipoprotein (Ox-LDL)-treated major histocompatibility complex class II
      (MHC II)-expressing APCs. Culture supernatant was collected for mouse IFN-gamma
      ELISA and cell proliferation was measured. RESULTS: Ox-LDL deposited
      predominantly in renal tubulointerstitial areas of RK, increased over time, and
      co-stained with lectin-like Ox-LDL receptor in affected renal tubular cells. Both
      Ox-LDL and renal-specific glycoprotein Tamm-Horsfall protein were identified in
      renal lymph nodes. Cells co-staining for major MHC II and Ox-LDL were observed in
      RK and draining renal lymph nodes after 5/6Nx. Similarly, Ox-LDL was also present
      in tubules after UUO, CD3-positive T cells were present in the interstitium, and
      Ox-LDL-treated MHC II-expressing APCs induced proliferation and IFN-gamma
      production in renal tubulointerstitial T lymphocytes isolated from kidneys after
      UUO. CONCLUSIONS: These data demonstrate that the tubulointerstitial inflammatory
      infiltrate that accompanies chronic kidney disease reflects, at least in part,
      the development of autoimmunity to novel antigens generated during renal injury.

PMID- 22653260
TI  - Cholangiocarcinoma and dominant strictures in patients with primary sclerosing
      cholangitis:  a 25-year single-centre experience.
AB  - BACKGROUND: Dominant biliary strictures occur commonly in patients with primary
      sclerosing cholangitis (PSC), who have a high risk of developing
      cholangiocarcinoma (CC). The natural history and optimal management of dominant
      strictures remain unclear, with some reports suggesting that endoscopic
      interventions improve outcome. METHODS: We describe a 25-year experience in
      patients with PSC-related dominant strictures at a single tertiary referral
      centre. RESULTS: A total of 128 patients with PSC (64% men, mean age at referral
      49 years) were followed for a mean of 9.8 years. Eighty patients (62.5%) with
      dominant biliary strictures had a median of 3 (range 0-34) interventions,
      compared with 0 (0-7) in the 48 patients without dominant strictures (P<0.001).
      Endoscopic interventions included the following: (i) stenting alone (46%), (ii)
      dilatation alone (20%), (iii) dilatation and stenting (17%) and (iv) none or
      failed intervention (17%, of whom most required percutaneous transhepatic
      drainage). The major complication rate for endoscopic retrograde
      cholangiopancreatography was low (1%). The mean survival of those with dominant
      strictures (13.7 years) was worse than that for those without dominant strictures
      (23 years), with much of the survival difference related to a 26% risk of CC
      developing only in those with dominant strictures. Half of those with CC
      presented within 4 months of the diagnosis of PSC, highlighting the importance of
      a thorough evaluation of new dominant strictures. CONCLUSION: Repeated endoscopic
      therapy in PSC patients is safe, but the prognosis remains worse in the subgroup
      with dominant strictures. In our series, dominant strictures were associated with
      a high risk of developing CC.

PMID- 22653261
TI  - Proteinase protection of prApe1 as a tool to monitor Cvt vesicle/autophagosome
      biogenesis.
AB  - Due in part to the increasing number of links between autophagy malfunction and
      human diseases, this field has gained tremendous attention over the past decade.
      Our increased understanding of the molecular machinery involved in macroautophagy
      (hereafter autophagy) seems to indicate that the most complex step, or at least
      the stage of the process where the majority of the autophagy-related (Atg)
      proteins participate, is in the formation of the double-membrane sequestering
      vesicle. Thus, it is important to establish reliable approaches to monitor this
      specific process. One of the most commonly used methods is morphological analysis
      by electron microscopy of the cytosolic vesicles used in the cytoplasm-to-vacuole
      targeting (Cvt) pathway and autophagy, or the single-membrane intralumenal
      products, termed Cvt or autophagic bodies, that are formed after the fusion of
      these vesicles with the yeast vacuole. This method, however, can be costly and
      time consuming, and reliable analysis requires expert input. Furthermore, it is
      extremely difficult to detect an incomplete autophagosome by electron microscopy
      because of the difficulty of obtaining a section that randomly cuts through the
      open portion of the phagophore. The primary Cvt pathway cargo, precursor
      amminopeptidase I (prApe1), is enwrapped within either a Cvt vesicle or
      autophagosome depending on the nutritional conditions. The proteolytic
      sensitivity of the prApe1 propeptide can therefore serve as a useful tool to
      determine the completion status of double-membrane Cvt vesicles/autophagosomes in
      the presence of exogenously added proteinase. Here, we describe an assay that
      examines the proteinase protection of prApe1 for determining the completion of
      Cvt vesicles/autophagosomes.

PMID- 22653264
TI  - Is Doppler ultrasonography essential for hemorrhoidal artery ligation?
AB  - BACKGROUND: Doppler ultrasonography enables accurate identification of the
      terminal branches of the superior rectal artery prior to hemorrhoidal artery
      ligation (HAL). However, since the positions of these branches have been found to
      be relatively constant, the question arises as to the necessity of
      ultrasonography for their identification. The aim of the current study was to
      examine the positions of all arteries identified and ligated during the HAL
      procedure. METHODS: We recorded the position of all arteries located and ligated
      in 135 consecutive patients who underwent the HAL procedure during the years 2003
      to 2006. RESULTS: In all patients, 6-8 terminal arterial branches were located
      above the dentate line. In 102 (76 %) patients, terminal branches were located in
      all 6 of the odd-numbered clock positions around the anus (1, 3, 5, 7, 9, and 11
      o'clock in the lithotomy position). If we had ligated arteries only at these odd
      numbered clock positions, without using Doppler ultrasonography, we would have
      located all the arteries in 96 (71 %) of our patients. CONCLUSIONS: The number
      and location of arterial branches of the superior rectal artery are relatively
      constant. Nevertheless, if, Doppler ultrasonography had not been performed and,
      ligation in the HAL procedure had been at the odd-numbered clock positions only,
      then at least one artery would have been missed in 29 % of our patients.

PMID- 22653265
TI  - Upregulation of Gp96 correlates with the radiosensitivity and five-year survival
      rate of nasopharyngeal carcinoma.
AB  - Gp96 (GRP94) is a chaperone that is responsible for molecular folding and
      assembly of proteins. To investigate correlations among Gp96 expression,
      sensitivity to radiotherapy and clinical features of nasopharyngeal carcinoma
      (NPC), the expression of Gp96 in 98 NPC samples was analyzed by
      immunohistochemistry and Western blotting at the protein level, and by real-time
      PCR at the mRNA level. Clinicopathological features, including stage, sex, grade
      and survival, were compared between the high and low Gp96 expression groups. As a
      result, Gp96 was expressed at a higher level in NPC tissues than in noncancerous
      nasopharyngeal mucosa (p = 0.001). Univariate analysis suggested that a higher
      Gp96 expression level was associated with significantly decreased disease-free
      and 5-year survival rates (p = 0.000, p = 0.000, respectively). Multivariate Cox
      proportional-hazard regression analysis, which adjusts for clinicopathological
      variables, indicated that it was only associated with the 5-year overall survival
      rate (p = 0.002). Furthermore, patients with high Gp96 expression levels were
      significantly more resistant to radiotherapy (p = 0.001). These data are the
      first indication of a positive correlation between Gp96 expression levels and
      radiosensitivity and 5-year survival rate. Gp96 might serve as a novel candidate
      marker for predicting the long-term prognostic outcome of NPC.

PMID- 22653267
TI  - Modulating breast milk composition - the key to allergy prevention?.

PMID- 22653268
TI  - Formation of MU(2)-hydroxo-bonded (MgPc)2OH- assemblies and (C60(-))2 dimers in
      ionic fullerene {(MgPc)2OH-}2.(C60(-))2.(cation+)4 complexes.
AB  - Ionic complexes containing MU(2)-hydroxo-bonded (MgPc)(2)OH(-) phthalocyanine
      assemblies and C(60)(-) anions: {(MgPc)(2)OH(-)}(2).(C(60)(
      ))(2).(PMDAE(+))(4).(C(6)H(5)CN)(4) (1); {(MgPc)(2)OH(-)}(2).(C(60)(
      ))(2).(TMP(+))(4).(C(6)H(5)CN)(3).(C(6)H(4)Cl(2))(2.5) (2) (where PMDAE(+) is the
      cation of N,N,N',N',N'-pentamethyldiaminoethane and TMP(+) is the N,N'N'
      trimethylpiperazinium cation) have been obtained as single crystals. The ionic
      ground state of the complexes is justified by the EPR spectra and the spectra in
      the IR and NIR ranges. The C(60)(-) radical anions are dimerized both in 1 and 2
      in the 240-220 K range. Dimerization is accompanied by the reversible transition
      of the complexes from paramagnetic to diamagnetic state. MgPc forms unusual
      (MgPc)(2)OH(-) assemblies, in which the hydroxo-anion coordinates to two MgPc
      molecules by a MU(2)-fashion. The length of the Mg-O bonds is 1.936-1.955(2) A,
      the Mg-O-Mg angle is 133.37-135.27(4) degrees  and the displacement of the Mg
      atoms out of the mean 24-atom phthalocyanine plane is 0.77-0.86 A. The packing of
      spherical fullerene and planar phthalocyanine molecules is attained in a crystal
      by the insertion of fullerenes between phenylene groups of phthalocyanines. It
      has been shown that metal phthalocyanines in ionic complexes with C(60) form
      M(II)Pc.(L(-)) assemblies, whereas metalloporphyrins form M(II)porphyrin.(C(+))
      assemblies.

PMID- 22653266
TI  - Comparative proteomics of two Vibrio anguillarum serotype O1 strains with
      different virulence phenotypes.
AB  - Vibrio anguillarum is part of the natural flora in the aquatic habitat, but under
      certain circumstances it can cause terminal hemorrhagic septicemia in marine fish
      due to the action of virulence-associated proteins. In our study, V. anguillarum
      MN and 3010 were identified as serotype O1 by AFLP analysis, and the virulence of
      V. anguillarum MN was shown 50-fold higher than that of the strain 3101 by LD(50)
      tests with Japanese flounder Paralichthys olivaceus. Nine spots were noted as
      differentially expressed proteins by comparing the cellular and extracellular
      protein profiles of V. anguillarum MN and 3101. Mass spectrometry results showed
      OmpU and PrtV were highly expressed in the virulent strain MN but lowly expressed
      in the less virulent strain 3101. Expression level confirmed by semiquantitative
      RT-PCR showed that ompU and prtV were indeed highly expressed in the virulent
      strain MN. Together with similar amino acid sequences of both OmpU and PrtV in V.
      anguillarum MN and 3101, our study indicated that the expression level of OmpU
      and PrtV may be associated with the virulence of V. anguillarum.

PMID- 22653269
TI  - Nanopores--the 'Holey Grail' in nanotechnology research.

PMID- 22653271
TI  - Myocardial strain abnormalities in fetal congenital heart disease assessed by
      speckle tracking echocardiography.
AB  - OBJECTIVES: To compare myocardial deformation patterns in fetuses with congenital
      heart disease (CHD) with our reference range using speckle tracking
      echocardiography. METHODS: We prospectively stored and analyzed 4-chamber loops
      of 28 fetuses with CHD (median gestation 27 weeks, range 20.9-37.0). The peak
      longitudinal left (LVs) and right (RVs) ventricular free wall Lagrangian strain
      and LV/RV strain ratio were measured from Syngo VVI software- (Siemens) derived
      original coordinates. Strain values from the first examination were compared with
      normative data from the same population using ANOVA with post hoc tests and
      serial examinations described in 14 fetuses. RESULTS: Simple shunt lesions (0.82)
      and shunts with pulmonary stenosis or atresia (0.93) had reduced mean LV/RV
      strain ratios compared to normal fetuses (1.01; 95% CI 0.97-1.05). Fetuses with
      hypoplastic left heart had the lowest (0.29), and those with Ebstein the highest
      (1.55), LV:RV ratio. Serial measurements showed increased LVs in aortic
      coarctation and aortic stenosis, but not in one developing important mitral
      regurgitation. Increased right ventricular loading in a fetus developing
      pulmonary regurgitation was associated with increasing RVs. CONCLUSIONS:
      Myocardial strain reflects the changing physiology of fetal CHD. Speckle tracking
      might be a useful tool to study the progress of myocardial function in affected
      fetuses.

PMID- 22653270
TI  - Deletion of p47phox attenuates the progression of diabetic nephropathy and
      reduces the severity of diabetes in the Akita mouse.
AB  - AIMS/HYPOTHESIS: Reactive oxygen species (ROS) contribute to diabetes-induced
      glomerular injury and endoplasmic reticulum (ER) stress-induced beta cell
      dysfunction, but the source of ROS has not been fully elucidated. Our aim was to
      determine whether p47(phox)-dependent activation of NADPH oxidase is responsible
      for hyperglycaemia-induced glomerular injury in the Akita mouse, a model of type
      1 diabetes mellitus resulting from ER stress-induced beta cell dysfunction.
      METHODS: We examined the effect of deleting p47 (phox) (also known as Ncf1), the
      gene for the NADPH oxidase subunit, on diabetic nephropathy in the Akita mouse
      (Ins2 (WT/C96Y)) by studying four groups of mice: (1) non-diabetic mice (Ins2
      (WT/WT)/p47 (phox+/+)); (2) non-diabetic p47 (phox)-null mice (Ins2 (WT/WT)/p47
      (phox-/-)); (3) diabetic mice: (Ins2 (WT/C96Y)/p47 (phox+/+)); and (4) diabetic
      p47 (phox)-null mice (Ins2 (WT/C96Y)/p47 (phox-/-)). We measured the urinary
      albumin excretion rate, oxidative stress, mesangial matrix expansion, and plasma
      and pancreatic insulin concentrations in 16-week-old mice; we also measured
      glucose tolerance and insulin sensitivity, islet and glomerular NADPH oxidase
      activity and subunit expression, and pro-fibrotic gene expression in 8-week-old
      mice. In addition, we measured NADPH oxidase activity, subunit expression and pro
      fibrotic gene expression in high glucose-treated murine mesangial cells. RESULTS:
      Deletion of p47 (phox) reduced kidney hypertrophy, oxidative stress and mesangial
      matrix expansion, and also reduced hyperglycaemia by increasing pancreatic and
      circulating insulin concentrations. p47 (phox-/-) mice exhibited improved glucose
      tolerance, but modestly decreased insulin sensitivity. Deletion of p47 (phox)
      attenuated high glucose-induced activation of NADPH oxidase and pro-fibrotic gene
      expression in glomeruli and mesangial cells. CONCLUSIONS/INTERPRETATION: Deletion
      of p47 (phox) attenuates diabetes-induced glomerular injury and beta cell
      dysfunction in the Akita mouse.

PMID- 22653275
TI  - Improving self-reports of active and sedentary behaviors in large epidemiologic
      studies.
AB  - Questionnaires that assess active and sedentary behaviors in large-scale
      epidemiologic studies are known to contain substantial errors. We present three
      options for improving measures of physical activity behaviors in large-scale
      epidemiologic studies, discuss the problems and prospects for each of these
      options, and highlight a new direction for measuring these behaviors in such
      studies.

PMID- 22653276
TI  - Select exercise modalities may reverse movement dysfunction because of peripheral
      neuropathy.
AB  - Peripheral neuropathy (PN) is a highly prevalent and potentially debilitating
      disease linked to mobility and postural control impairments and movement
      dysfunction in goal-directed movements. Although different exercises have
      produced functional improvements in PN, recent evidence indicates that exercises
      like Tai Chi can alter the damaged sensory system and facilitate recovery of
      mobility and balance, potentially reducing the reliance on other people.

PMID- 22653277
TI  - A dual mechanism of action for skeletal muscle FAT/CD36 during exercise.
AB  - Carnitine palmitoyltransferase I has been viewed historically as the sole
      regulator of fatty acid oxidation. However, we have identified fatty acid
      translocase/CD36 as an additional control point. Specifically, fatty acid
      translocase/CD36 seems to have a novel dual mechanism of action with regard to
      fatty acid oxidation during exercise, influencing transport of lipids across the
      sarcolemmal membrane and into the mitochondria.

PMID- 22653278
TI  - Metabolic dysfunction under reduced estrogen levels:  looking to exercise for
      prevention.
AB  - Loss of estrogen function leads to the development of metabolic dysfunction that
      spans numerous tissues. In this review, we explore the concept that estrogens are
      critical for defining metabolic function in adipose and hepatic tissues and also
      the possibility that exercise training should be considered a substitute for
      estrogen replacement therapy in women with impairments in estrogen levels.

PMID- 22653279
TI  - Effectiveness of preacclimatization strategies for high-altitude exposure.
AB  - Acute mountain sickness (AMS) and large decrements in endurance exercise
      performance occur when unacclimatized individuals rapidly ascend to high
      altitudes. Six altitude and hypoxia preacclimatization strategies were evaluated
      to determine their effectiveness for minimizing AMS and improving performance
      during altitude exposures. Strategies using hypobaric chambers or true altitude
      were much more effective overall than those using normobaric hypoxia (breathing,
      <20.9% oxygen).

PMID- 22653280
TI  - Comparison of three multichannel transmit/receive radiofrequency coil
      configurations for anatomic and functional cardiac MRI at 7.0T: implications for
      clinical imaging.
AB  - OBJECTIVES: To implement, examine, and compare three multichannel
      transmit/receive coil configurations for cardiovascular MR (CMR) at 7T. METHODS:
      Three radiofrequency transmit-receive (TX/RX) coils with 4-, 8-, and 16-coil
      elements were used. Ten healthy volunteers (seven males, age 28 +/- 4 years)
      underwent CMR at 7T. For all three RX/TX coils, 2D CINE FLASH images of the heart
      were acquired. Cardiac chamber quantification, signal-to-noise ratio (SNR)
      analysis, parallel imaging performance assessment, and image quality scoring were
      performed. RESULTS: Mean total examination time was 29 +/- 5 min. All images
      obtained with the 8- and 16-channel coils were diagnostic. No significant
      difference in ejection fraction (EF) (P > 0.09) or left ventricular mass (LVM) (P
      > 0.31) was observed between the coils. The 8- and 16-channel arrays yielded a
      higher mean SNR in the septum versus the 4-channel coil. The lowest geometry
      factors were found for the 16-channel coil (mean +/- SD 2.3 +/- 0.5 for R = 4).
      Image quality was rated significantly higher (P < 0.04) for the 16-channel coil
      versus the 8- and 4-channel coils. CONCLUSIONS: All three coil configurations are
      suitable for CMR at 7.0T under routine circumstances. A larger number of coil
      elements enhances image quality and parallel imaging performance but does not
      impact the accuracy of cardiac chamber quantification. KEY POINTS : * Cardiac
      chamber quantification using 7.0T magnetic resonance imaging is feasible. *
      Examination times for cardiac chamber quantification at 7.0T match current
      clinical practice. * Multichannel transceiver RF technology facilitates improved
      image quality and parallel imaging performance. * Increasing the number of RF
      channels does not influence cardiac chamber quantification.

PMID- 22653281
TI  - Early diffusion weighted magnetic resonance imaging can predict survival in women
      with locally advanced cancer of the cervix treated with combined chemo-radiation.
AB  - OBJECTIVES: To assess the predictive value of diffusion weighted imaging (DWI)
      for survival in women treated for advanced cancer of the cervix with concurrent
      chemo-radiotherapy. METHODS: Twenty women treated for advanced cancer of the
      cervix were recruited and followed up for a median of 26 (range <1 to 43) months.
      They each had DWI performed before treatment, 2 weeks after beginning therapy
      (midtreatment) and at the end of treatment. Apparent diffusion coefficient (ADC)
      values were calculated from regions of interest (ROI). All participants were
      reviewed for follow-up data. ADC values were compared with mortality status (Mann
      Whitney test). Time to progression and overall survival were assessed (Kaplan
      Meier survival graphs). RESULTS: There were 14 survivors. The median midtreatment
      ADC was statistically significantly higher in those alive compared to the non
      survivors, 1.55 and 1.36 (*10(-3)/mm(2)/s), respectively, P = 0.02. The median
      change in ADC 14 days after treatment commencement was significantly higher in
      the alive group compared to non-survivors, 0.28 and 0.14 (*10(-3)/mm(2)/s),
      respectively, P = 0.02. There was no evidence of a difference between survivors
      and non-survivors for pretreatment baseline or post-therapy ADC values.
      CONCLUSION: Functional DWI early in the treatment of advanced cancer of the
      cervix may provide useful information in predicting survival. KEY POINTS : *
      Diffusion weighted magnetic resonance imaging (DWI) is increasingly used in
      cervical cancer. * Functional DWI early in treatment of cervical cancer may help
      predict survival. * DWI may help clinicians to tailor or individualise treatment
      appropriately. * This may limit toxicity from ineffective treatment and allow
      early alternative therapy.

PMID- 22653283
TI  - Dynamic contrast-enhanced 3-T MR imaging in cervical cancer before and after
      concurrent chemoradiotherapy.
AB  - OBJECTIVE: To investigate the changes of dynamic contrast-enhanced MR imaging
      (DCE-MRI) parameters at 3 T in cervical cancer patients before and after
      concurrent chemoradiotherapy (CCRT), and to correlate the parameters with final
      tumour response to therapy. METHODS: Thirty-five patients with cervical cancer
      underwent DCE-MRI before CCRT, 4 weeks after starting therapy and at 1 month
      after the end of therapy. DCE-MRI parameters were calculated in the tumour and
      normal gluteus muscle. Final response to treatment as determined by changes in
      tumour size and volume was correlated with pre-treatment DCE-MRI parameters.
      RESULTS: DCE-MRI parameters (i.e. K (trans), v (e) and k (ep)) in the tumours
      showed significant changes in response to CCRT (P < 0.05) and in particular K
      (trans) and v (e) demonstrated early significant increase (P < 0.01), but those
      in normal muscle did not show a significant difference (P > 0.05). Before
      therapy, the mean values of K (trans), k (ep), v (e) and v (p) in the tumours
      were significantly greater than those in muscle (P < 0.05). DCE-MRI parameters of
      the tumours at pre-treatment were not statistically associated with final tumour
      size or volume change. CONCLUSION: DCE-MRI parameters may help evaluate early
      changes of cervical cancer to CCRT, but larger, more definitive studies are
      needed. KEY POINTS : * DCE-MRI offers new insights into tumour behaviour. *
      Changes in tumour size lag behind biomarkers which improve quickly in responders.
      * DCE-MRI is a non-invasive imaging technique that can characterize tumour
      vasculature. * DCE-MRI of cervical cancer may be useful in monitoring changes
      with therapy.

PMID- 22653282
TI  - Assessment of pulmonary melanoma metastases with 18F-FDG PET/CT: which PET
      negative patients require additional tests for definitive staging?
AB  - OBJECTIVES: To determine, in patients with melanoma, the dependence of PET
      sensitivity on pulmonary metastasis size, and to determine patients who require
      further evaluation for definite staging. METHODS: Of 183 melanoma patients who
      underwent (18)F-fluorodeoxyglucose PET/computed tomography (CT) for staging or
      follow-up between January 2008 and June 2011, 38 patients (18 women and 20 men;
      mean age 62.0 +/- 14.7 years) with one or more pulmonary metastases visible on CT
      were included in the retrospective study. Each pulmonary metastasis was rated as
      positive or negative on PET, and lesion size (maximum transverse diameter) was
      assessed on CT. PET sensitivity was calculated according to the lesions' size, in
      2-mm steps. RESULTS: A total of 181 pulmonary metastases were analysed. PET
      sensitivity was 7.9 % for lesions of 4-5 mm; 33.3 % for lesions of 6-7 mm; 56.8 %
      for lesions of 8-9 mm; 63.6 % for lesions of 10-11 mm; 100 % for lesions of 12-14
      mm; and 100 % for lesions of at least 15 mm. The differences in sensitivity
      between the size groups were significant (P < 0.001) CONCLUSIONS: With current
      state-of-the-art PET/CT technology, additional tests are necessary for definitive
      staging of melanoma patients who have one or more PET-negative lung nodules less
      than 12 mm in diameter on expiratory CT. KEY POINTS : * PET cannot rule out
      malignancy in pulmonary nodules less than 12 mm on expiratory CT. * Melanoma
      patients with PET-negative pulmonary nodules less than 12 mm require additional
      tests. * Knowledge of these factors can help interpretation of PET and PET/CT
      findings.

PMID- 22653284
TI  - Controllable labelling of stem cells with a novel superparamagnetic iron oxide
      loaded cationic nanovesicle for MR imaging.
AB  - OBJECTIVE: To investigate the feasibility of highly efficient and controllable
      stem cell labelling for cellular MRI. METHODS: A new class of cationic,
      superparamagnetic iron oxide nanoparticle (SPION)-loaded nanovesicles was
      synthesised to label rat bone marrow mesenchymal stem cells without secondary
      transfection agents. The optimal labelling conditions and controllability were
      assessed, and the effect of labelling on cell viability, proliferation activity
      and multilineage differentiation was determined. In 18 rats, focal ischaemic
      cerebral injury was induced and the rats randomly injected with 1 * 10(6) cells
      labelled with 0-, 8- or 20-mV nanovesicles (n = 6 each). In vivo MRI was
      performed to follow grafted cells in contralateral striata, and results were
      correlated with histology. RESULTS: Optimal cell labelling conditions involved a
      concentration of 3.15 MUg Fe/mL nanovesicles with 20-mV positive charge and 1-h
      incubation time. Labelling efficiency showed linear change with an increase in
      the electric potentials of nanovesicles. Labelling did not affect cell viability,
      proliferation activity or multilineage differentiation capacity. The distribution
      and migration of labelled cells could be detected by MRI. Histology confirmed
      that grafted cells retained the label and remained viable. CONCLUSION: Stem cells
      can be effectively and safely labelled with cationic, SPION-loaded nanovesicles
      in a controllable way for cellular MRI. KEY POINTS: * Stem cells can be
      effectively labelled with cationic, SPION-loaded nanovesicles. * Labelling did
      not affect cell viability, proliferation or differentiation. * Cellular uptake of
      SPION could be controlled using cationic nanovesicles. * Labelled cells could
      migrate along the corpus callosum towards cerebral infarction. * The grafted,
      labelled cells retained the label and remained viable.

PMID- 22653285
TI  - Detection of symptomatic vasospasm after subarachnoid haemorrhage: initial
      findings from single time-point and serial measurements with arterial spin
      labelling.
AB  - OBJECTIVES: To detect symptomatic hemispheres during the postoperative course of
      subarachnoid haemorrhage (SAH) using arterial spin labelling (ASL). METHODS:
      Eighteen patients with aneurysmal SAH were included; four exhibited symptomatic
      vasospasm postoperatively. All patients underwent ASL on days 9-10 (single time
      point ASL). Nine patients underwent serial measurements of ASL (serial ASL) on
      days 1-2, 9-10 and 13-21, and seven patients also underwent imaging on days 4-7.
      CBF in the posterior part of the MCA territory was measured, and the
      ipsilateral/contralateral ratio of CBF was calculated. Differences between
      symptomatic hemispheres and others underwent ROC analysis. RESULTS: Single time
      point ASL revealed that CBF(day9-10) and CBF(i/c_day9-10) were significantly
      lower in symptomatic hemispheres than in asymptomatic hemispheres (P < 0.001).
      Serial ASL was significantly decreased on CBF(day4-7) compared with CBF(day1-2)
      and on CBF(day9-10) compared with CBF(day4-7), and significantly increased on
      CBF(day13-21) compared with CBF(day9-10). ROC analysis of single time-point ASL
      revealed that AUC for CBF(day9-10) was 0.95, significantly higher than
      CBF(i/c_day9-10) (P < 0.001). ROC analysis of serial ASL showed that AUC for
      CBF(day9-10) was 0.93 and significantly higher than CBF(day9-10/day1-2) and
      CBF(i/c_day9-10) (P < 0.001). CONCLUSIONS: Single time-point ASL revealed
      significant CBF reduction in symptomatic hemispheres compared with asymptomatic
      hemispheres. Serial ASL showed time-dependent CBF changes after SAH. KEY POINTS :
      * MR arterial spin labelling (ASL) can non-invasively assess cerebral blood flow
      (CBF) * ASL revealed significant CBF reduction in symptomatic hemispheres
      compared with asymptomatic hemispheres * Serial ASL measurements enable
      observation of time-dependent CBF changes after SAH * ASL is non- invasive and
      suitable for serial repeated examinations.

PMID- 22653286
TI  - Tumour size of resectable oesophageal squamous cell carcinoma measured with
      multidetector computed tomography for predicting regional lymph node metastasis
      and N stage.
AB  - OBJECTIVES: To determine whether and how tumour size of resectable oesophageal
      squamous cell carcinoma (ESCC) measured with multidetector CT could predict
      regional lymph node metastasis (LNM) and N stage. METHODS: Two hundred five
      patients with ESCC underwent radical oesophagectomy with three-field
      lymphadenectomy less than 3 weeks after contrast-enhanced CT. Tumour size of the
      ESCC (tumour length, maximal thickness and gross tumour volume, GTV) was measured
      on CT. Statistical analyses were performed to identify whether tumour size could
      predict regional LNM and N stage, and to determine how to use the size of ESCC to
      predict N stage. RESULTS: Univariate analysis showed that tumour size could
      predict regional LNM (all P < 0.05). Logistic regression analysis revealed that
      GTV could independently predict regional LNM (P = 0.021, odds ratio = 1.813).
      Mann-Whitney tests showed that tumour size could distinguish grouped N stages
      (all P < 0.05). GTV might be a differentiating indicator between N0 and N1-3
      stages (cutoff, 14.4 cm(3)), between N0-1 and N2-3 (cutoff, 15.9 cm(3)), and
      between N0-2 and N3 (cutoff, 26.1 cm(3)), with sensitivity of 76%, 63% or 75%,
      and specificity of 75%, 61% and 81%, respectively. CONCLUSIONS: The GTV of ESCC
      measured with CT could be an indicator for predicting regional LNM and grouped N
      stages. KEY POINTS : * Multidetector computed tomography (MDCT) allows accurate
      assessment of oesophageal tumour size * For resectable squamous cell tumours,
      size helped predict regional lymph node involvement * Gross tumour volume may
      predict the N stage of oesophageal squamous cell carcinoma.

PMID- 22653287
TI  - Safety and efficacy of US-guided high-intensity focused ultrasound for treatment
      of submucosal fibroids.
AB  - OBJECTIVES: To evaluate the safety and efficacy of US-guided high-intensity
      focused ultrasound (HIFU) ablation for the treatment of submucosal fibroids
      METHODS: A total of 76 women with 78 submucosal uterine fibroids (68 type II
      fibroids, 10 type I fibroids) underwent US-guided HIFU ablation. The pretreatment
      fibroid diameter ranged from 2.4 to 13.5 cm (mean 5.7 +/- 2.3 cm). The fibroids
      were ablated using a power output of 420-520 W. During follow-up, the volume
      shrinkage of the ablated fibroids was continuously observed on contrast-enhanced
      MR and/or contrast-enhanced ultrasound (CEUS). The change of symptoms was
      evaluated by using the symptom severity score questionnaire. RESULTS: HIFU
      ablation was well tolerated in all patients. No major complications occurred. The
      mean nonperfused ablation ratio was 80 +/- 12 % on CEUS. During follow-up, the
      ablated fibroids shrank significantly over time. The symptoms were alleviated
      significantly. No patients had amenorrhoea after treatment. Vaginal expulsion of
      necrotic tissue was seen in 58 % (44/76) of patients after HIFU ablation which
      disappeared after 2-4 menstrual cycles. Four patients received repeated HIFU
      ablation for enlarged residual fibroids. CONCLUSIONS: US-guided HIFU ablation may
      be a safe and effective treatment for submucosal fibroids. Further studies are
      warranted to observe its influence on fertility. KEY POINTS : * High-intensity
      focused ultrasound (HIFU) is a new minimally invasive therapeutic technique. *
      HIFU ablation may be safe and effective for treatment of submucosal fibroids *
      Treatment is minimally invasive and repeatable. * Vaginal expulsion of necrotic
      tissue is common after treatment.

PMID- 22653288
TI  - Thrombus imaging in acute ischaemic stroke using thin-slice unenhanced CT:
      comparison of conventional sequential CT and helical CT.
AB  - OBJECTIVES: Thin-slice helical unenhanced CT can be used for thrombus imaging but
      increases radiation exposure. Conventional sequential images obtained by
      multidetector CT can be reconstructed into thin-slice images. The purpose of this
      study was to evaluate if conventional sequential unenhanced CT images can replace
      helical unenhanced CT for thrombus imaging. METHODS: Fifty consecutive patients
      with acute ischaemic stroke underwent both 5-mm conventional sequential
      unenhanced CT and helical unenhanced CT. Each of the sequential and helical
      unenhanced CT images was subsequently reconstructed into four 1.25-mm images.
      Thrombus volumes and HU were measured semi-automatically using both types of
      unenhanced CT. Thrombus HU ratio (rHU) was calculated using the HU of the
      contralateral segment. The intraclass correlation coefficient (ICC) and Bland
      Altman plots were used to assess measurement agreement. RESULTS: The mean rHUs
      were 1.47 +/- 0.17 for sequential unenhanced CT and 1.47 +/- 0.18 helical
      unenhanced CT (P = 0.542). The mean thrombus volumes were 124.25 +/- 125.65 mm(3)
      and 117.84 +/- 124.32 mm(3) on sequential and helical unenhanced CT images,
      respectively (P = 0.063). Measurement agreement between thrombus volumes from the
      two unenhanced CT images was high (ICC = 0.981). CONCLUSIONS: Thin-slice
      unenhanced CT images reconstructed from 5-mm sequential images can replace
      helical unenhanced CT for thrombus imaging in acute ischaemic stroke. KEY POINTS
      : * Unenhanced CT is used to evaluate intra-arterial thrombus. * Thrombus HU and
      volume measurements using sequential or helical CT are comparable. * Conventional
      sequential images can replace helical CT for thrombus imaging. * Radiation dose
      for thrombus imaging can be reduced using sequential CT.

PMID- 22653289
TI  - Use of mesenchymal stem cells and darbepoetin improve ischemia-induced acute
      kidney injury outcomes.
AB  - BACKGROUND: Interest has recently been focused on the possible role of bone
      marrow-originating stem cells and the therapeutic role of erythropoietin in the
      recovery of ischemia-induced acute kidney injury (AKI). The aim of the present
      study was to compare treatment with mesenchymal stem cells (MSCs) to treatment
      with darbepoetin-alpha (DPO) or both concomitantly in a rat model of
      ischemia/reperfusion (I/R) AKI. METHODS: Forty male Sprague-Dawley rats were
      included, and 28 of them were randomly assigned to controls (treated with serum
      physiologic) or one of the three treatment groups treated with either DPO, MSCs,
      or both (MSCs and DPO concomitantly) after the induction of I/R injury.
      Hematocrit, serum creatinine, and BUN levels were obtained at 0, 24, 48, and 72 h
      of surgery, and renal tissue was obtained at 72 h after nephrectomy for
      histological analysis. Tissue injury was quantified by standardized histological
      scoring systems, using light and electron microscopes. RESULTS: Treatment with
      MSCs or DPO improved renal function compared with controls. However, the
      improvement observed in renal function in the MSC/DPO group was better than that
      in the other groups. Histological analysis demonstrated that tissue injury was
      significantly decreased in rats in the MSC or DPO groups compared to that of the
      controls; however the best recovery was observed in rats treated with MSCs and
      DPO concomitantly. CONCLUSION: These results suggest that concomitant application
      of DPO and MSCs may be a potential novel renoprotective therapy for patients
      after having sustained an ischemic renal insult.

PMID- 22653291
TI  - Chest physiotherapy during an acute exacerbation of chronic obstructive pulmonary
      disease.

PMID- 22653293
TI  - Heidelberg Coping Scales for Delusions: psychometric evaluation of an expert
      rating instrument.
AB  - BACKGROUND: Coping is of substantial relevance in the treatment and course of
      psychiatric disorders. Standardized instruments to assess coping with psychotic
      symptoms, particularly delusions, are rare. The aim of this study was to develop
      and evaluate the psychometric properties of a new instrument to assess coping
      strategies in the context of delusional experiences: the Heidelberg Coping Scales
      for Delusions (HCSD). METHODS: Two hundred and twelve inpatients with
      schizophrenia spectrum disorders and affective disorders currently experiencing
      delusions were interviewed with the HCSD and other coping assessment instruments.
      Psychometric properties and factor structure were analyzed. RESULTS: The HCSD
      showed good inter-rater reliability and convergent validity. Factor analysis
      yielded an interpretable structure with five factors: resource-oriented coping,
      medical care, distraction, cognitive coping, and depressive coping. Symptomatic
      behavior, due to its particular characteristics, was considered apart.
      CONCLUSION: The HCSD is a reliable and valid instrument for the assessment of
      coping strategies in patients with delusions. Further research is needed to
      evaluate coping changes over time and their influence on treatment and clinical
      outcomes.

PMID- 22653292
TI  - Asthma endophenotypes and polymorphisms in the histamine receptor HRH4 gene.
AB  - BACKGROUND: Histamine as an inflammatory mediator plays an important role in
      chronic allergic and asthmatic conditions. However, the role of genetic
      polymorphisms of the histamine receptor HRH4 (histamine receptor H4) gene in
      asthma susceptibility and endophenotypes has not been studied yet. Our aim was to
      investigate the possible association between single nucleotide polymorphisms
      (SNPs) in the HRH4 gene and asthma or some endophenotypes of asthma. METHODS:
      Twenty-one SNPs of the HRH4 gene were genotyped in 313 asthmatic patients and 360
      controls using Sequenom(r) iPLEX(r) Gold Genotyping Technology. RESULTS: Genotype
      distribution of three HRH4 SNPs, namely rs17187619 [p = 0.002; odds ratio, OR
      (95% confidence interval, CI) = 2.4 (4.1-1.4)], rs527790 [p = 0.0002; OR (95% CI)
      = 3.3 (6.1-1.8)] and rs487202 [p = 0.00007; OR (95% CI) = 3.5 (6.6-1.9)] differed
      significantly between patients with or without infection-induced asthma.
      Haplotypes, which included the rs4800573-rs527790 CC allele combination, were
      found to be associated with infection-induced asthma [p = 0.0009, OR (95% CI) =
      0.5 (0.4-0.8)]. The rs487202-rs574913 CA haplotype was more frequent among
      patients with infection-induced asthma [p = 0.0006, OR (95% CI) = 1.9 (1.3-2.6)].
      None of the SNPs contributed directly to the risk of asthma. CONCLUSIONS: Our
      results suggest that genetic variation in the HRH4 gene might influence the
      pathogenesis of infection-induced asthma.

PMID- 22653295
TI  - Type II TGFbeta receptor modulates chondrocyte phenotype.
AB  - Aging is one of the major risk factors of osteoarthritis. This pathology during
      which chondrocytes undergo modifications of their phenotype may result from
      alteration of transforming growth factor beta (TGFbeta) signaling. This study
      investigates the role of TGFbeta response in the process of chondrocyte
      dedifferentiation/redifferentiation. Dedifferentiation was induced by successive
      passages of human articular chondrocytes, whereas their redifferentiation was
      performed by three-dimensional culture in alginate. Human mesenchymal stem cells
      were obtained from bone marrow and differentiated into chondrocyte-like phenotype
      by three-dimensional culture, embedded in the same scaffold. Protein and mRNA
      levels were analyzed by Western blot and real-time reverse transcription PCR.
      Regulatory mechanism was investigated using specific inhibitors (mithramycin),
      mRNA silencing or decoy oligonucleotides, and expression vectors. Chondrocyte
      dedifferentiation interfered with TGFbeta signaling by decreasing TbetaRII mRNA
      and protein levels and subsequent TGFbeta response. TbetaRII ectopic expression
      in passaged chondrocytes permitted to increase the expression of several matrix
      genes, such as aggrecan or type II collagen. Redifferentiation of passaged
      chondrocytes permitted to restore, at least in part, TbetaRII expression and was
      related to differentiation of human bone marrow mesenchymal stem cells toward
      chondrocytes, where both specific protein 1 (Sp1) and TbetaRII mRNA levels were
      increased. Moreover, Sp1 manipulation by silencing or ectopic expression and
      pharmacologic inhibition revealed a link between expression levels of this
      transcriptional factor, which is crucial for constitutive expression of TbetaRII
      in cartilage, and TGFbeta response. Therefore, these data permit us to suggest an
      important role of TbetaRII expression in the maintenance of chondrocyte
      phenotype, which is altered with age, and bring new insights in our understanding
      of chondrogenesis process. 

PMID- 22653298
TI  - Dietary lipids and aging compromise chaperone-mediated autophagy by similar
      mechanisms.
AB  - Chaperone-mediated autophagy (CMA) is a selective form of autophagy whose
      distinctive feature is the fact that substrate proteins are translocated directly
      from the cytosol across the lysosomal membrane for degradation inside lysosomes.
      CMA substrates are cytosolic proteins bearing a pentapeptide motif in their
      sequence that, when recognized by the cytosolic chaperone HSPA8/HSC70, targets
      them to the surface of the lysosomes. Once there, substrate proteins bind to the
      lysosome-associated membrane protein type 2 isoform A (LAMP2A), inducing assembly
      of this receptor protein into a higher molecular weight protein complex that is
      used by the substrate proteins to reach the lysosomal lumen. CMA is
      constitutively active in most cells but it is maximally activated under
      conditions of stress.

PMID- 22653297
TI  - Curcumin-supplemented diets increase superoxide dismutase activity and mean
      lifespan in Drosophila.
AB  - Curcumin is a polyphenolic bioactive compound in turmeric. We examined if
      antioxidant effects of curcumin are associated with lifespan extension in
      Drosophila. In this experiment, females and males of Drosophila were fed diets
      either containing no curcumin (C0) or supplemented with curcumin at 0.5 (C1) and
      1.0 (C2) mg/g of diet. The levels of malondialdehyde (MDA), enzyme activity of
      superoxide dismutase (SOD), and expression of seven age-related genes in females
      and males were analyzed. We found that C1 and C2 increased mean lifespan by 6.2 %
      and 25.8 % in females, and by 15.5 % and 12.6 % in males, respectively.
      Meanwhile, C1 and C2 significantly decreased MDA levels and increased SOD
      activity in both genders. Diets C1 in females and C2 in males are effective in
      extending mean lifespan and improving levels of two physiological and biochemical
      measures related to aging in Drosophila. Lifespan extension of curcumin in
      Drosophila was associated with the up-regulation of Mn-SOD and CuZn-SOD genes,
      and the down-regulation of dInR, ATTD, Def, CecB, and DptB genes. The present
      results suggest that curcumin increases mean lifespan of Drosophila via
      regulating gene expression of the key enzyme SOD and reducing accumulation of MDA
      and lipid peroxidation. This study provided new insights for understanding the
      anti-aging mechanism of curcumin in Drosophila.

PMID- 22653296
TI  - Effects of aging and sex on voluntary activation and peak relaxation rate of
      human elbow flexors studied with motor cortical stimulation.
AB  - Data are equivocal on whether voluntary activation is preserved or decreased in
      old compared to young adults. Further, data are scant on the effect of age on the
      rate of muscle relaxation when the muscle is contracting voluntarily. Assessment
      of both measures with transcranial magnetic stimulation (TMS) yields information
      which cannot be obtained with traditional peripheral nerve stimulation. Hence,
      voluntary activation and peak relaxation rate of the elbow flexors were assessed
      with TMS during repeated maximal efforts in 30 men and 28 women between the ages
      of 22-84 years. Voluntary activation was similar for the two sexes (P = 0.154)
      and was not affected by age in men (96.2 +/- 2.7 %; P = 0.887) or women (95.1 +/-
      3.0 %; P = 0.546). Men had a significantly faster peak rate of relaxation than
      women in absolute units (-880.0 +/- 223.2 vs. -360.2 +/- 78.5 Nm/ s,
      respectively; P < 0.001) and when normalized to subject strength (-12.5 +/- 2.1
      vs. -8.7 +/- 1.0 s(-1), respectively; P < 0.001). Absolute and normalized
      relaxation rates slowed with age in men (P = 0.002 and P = 0.006, respectively),
      but not women (P = 0.142 and P = 0.950, respectively). Across the age range
      studied, all subjects, regardless of age or sex, were able to achieve high
      voluntary activation scores for the elbow flexors (~95 %). In contrast, peak
      relaxation rate was markedly faster in men than women and slowed with age in men
      but not women. Normalization of relaxation rates to strength did not affect the
      influence of age or sex.

PMID- 22653305
TI  - Phytotoxicity of atrazine, S-metolachlor, and permethrin to Typha latifolia
      (Linneaus) germination and seedling growth.
AB  - Phytotoxicity assessments were performed to compare responses of Typha latifolia
      (L.) seeds to atrazine (only) and atrazine + S-metolachlor exposure
      concentrations of 0.03, 0.3, 3, and 30 mg L(-1), as well as permethrin exposure
      concentrations of 0.008, 0.08, 0.8, and 8 mg L(-1). All atrazine + S-metolachlor
      exposures resulted in significantly reduced radicle development (p < 0.001). A
      stimulatory effect for coleoptile development was noted in the three highest
      atrazine (only) exposures (p = 0.0030, 0.0181, and 0.0016, respectively). This
      research provides data concerning the relative sensitivity of T. latifolia seeds
      to pesticides commonly encountered in agricultural settings, as well as critical
      understanding and development of using T. latifolia in phytoremediation efforts
      for pesticide exposures.

PMID- 22653299
TI  - Excretion and metabolism of milnacipran in humans after oral administration of
      milnacipran hydrochloride.
AB  - The pharmacokinetics, excretion, and metabolism of milnacipran were evaluated
      after oral administration of a 100-mg dose of [14C]milnacipran hydrochloride to
      healthy male subjects. The peak plasma concentration of unchanged milnacipran
      (~240 ng/ml) was attained at 3.5 h and was lower than the peak plasma
      concentration of radioactivity (~679 ng Eq of milnacipran/ml) observed at 4.3 h,
      indicating substantial metabolism of milnacipran upon oral administration.
      Milnacipran has two chiral centers and is a racemic mixture of cis isomers: d
      milnacipran (1S, 2R) and l-milnacipran (1R, 2S). After oral administration, the
      radioactivity of almost the entire dose was excreted rapidly in urine
      (approximately 93% of the dose). Approximately 55% of the dose was excreted in
      urine as unchanged milnacipran, which contained a slightly higher proportion of d
      milnacipran (~31% of the dose). In addition to the excretion of milnacipran
      carbamoyl O-glucuronide metabolite in urine (~19% of the dose), predominantly as
      the l-milnacipran carbamoyl O-glucuronide metabolite (~17% of the dose),
      approximately 8% of the dose was excreted in urine as the N-desethyl milnacipran
      metabolite. No additional metabolites of significant quantity were excreted in
      urine. Similar plasma concentrations of milnacipran and the l-milnacipran
      carbamoyl O-glucuronide metabolite were observed after dosing, and the maximum
      plasma concentration of l-milnacipran carbamoyl O-glucuronide metabolite at 4 h
      after dosing was 234 ng Eq of milnacipran/ml. Lower plasma concentrations (<25 ng
      Eq of milnacipran/ml) of N-desethyl milnacipran and d-milnacipran carbamoyl O
      glucuronide metabolites were observed.

PMID- 22653306
TI  - Toxicological effect of herbicides (diuron and bentazon) on snake venom and
      electric eel acetylcholinesterase.
AB  - The toxicological effects of the active ingredients of the herbicides diuron and
      bentazon on the activity of acetylcholinesterase (AChE) of krait (Bungarus
      sindanus) venom and electric eel (Electrophorus electricus) were studied. The
      diuron and entazon caused non-competitive inhibition of AChE from both species.
      For the venom AChE, the calculated IC50 for diuron and bentazon were found to be
      3.25 and 0.14 MUM, while for eel AChE, the respective IC50 values were 3.6 and
      0.135 MUM. In comparison, bentazon was a more potent inhibitor than diuron of
      AChE from both species. The insecticide lindane did not have any inhibitory
      effect on AChE activity in either species, even when tested at high
      concentrations (200-800 MUM).

PMID- 22653307
TI  - Effects of olive oil mill waste water (OMWW) on the frog larvae.
AB  - In this research, acute effect of the olive oil mill wastewater (OMWW) on the
      frog larvae has been studied. Larvae showed hyperactivity symptoms first and loss
      of balance and remained motionless due to toxicity of wastewater. Toxicity was
      observed between 2 and 159 min depending on the test concentrations. Upon
      removing the phenolic compounds from the OMWW, this effect was seen after 248
      min. Potential effects of the OMWW in Lake Iznik were also researched. Salinity
      of the lake water changed from 0.2 0/00 to 0.0 0/00 respectively in the
      measurements done in May and December.

PMID- 22653308
TI  - Metal contamination and health risk from consumption of organically grown
      vegetables influenced by atmospheric deposition in a seasonally dry tropical
      region of India.
AB  - Pot-culture experiments showed that organically grown Vicia faba, influenced by
      atmospheric deposition, accumulated (MUg g(-1)) 0.088-3.246 Cadmium, 0.19-42.48
      Chromium, 0.0124-30.43 Copper, 0.075-4.28 Lead and 0.63-67.68 Zinc. Similar
      trends appeared for Abelmoschus esculentus. At high deposition sites, Cadmium,
      Lead and Zinc exceeded the safe limits of Prevention of Food Adulteration
      standards. Health risk index for Cadmium, Copper and Lead exceeded the safe
      limits of United States Environmental Protection Agency. The study suggests that
      atmospheric deposition could substantially elevate metal levels in organically
      grown vegetables in 2011.

PMID- 22653309
TI  - Phosphate binding to the [Au(IPr)] moiety: inner vs. outer sphere coordination
      behaviour.
AB  - The synthesis and characterization of a new class of cationic (NHC)gold(I) (NHC =
      N-Heterocyclic carbene) complex containing the phosphate counterions TRISPHAT and
      TRISPHAT-N have been achieved. The selection of the appropriate hexacoordinated
      phosphate architecture permits the isolation of complexes bearing an inner or
      outer sphere anionic counterion.

PMID- 22653310
TI  - Two-dimensional strain and twist by vector velocity imaging in adolescents with
      severe obesity.
AB  - The prevalence of severe obesity is increasing worldwide in adolescents. Whether
      it is associated with functional myocardial abnormalities remains largely
      unknown, potentially because of its frequent association with other
      cardiovascular risk factors and also use of insensitive techniques to detect
      subclinical changes in myocardial function. We used 2D vector velocity imaging
      (VVI) to investigate early changes in left ventricular (LV) myocardial function
      in youths with isolated severe obesity. Thirty-seven asymptomatic severely obese
      adolescents free of diabetes and hypertension, and 24 lean controls were
      enrolled. LV longitudinal, basal, and apical circumferential strain, strain rate
      (SR), rotations, and LV twist were measured. Obese adolescents had greater LV
      mass and reduced systolic and early diastolic tissue Doppler imaging (TDI)
      velocities than lean counterparts. L strain (-24%) and systolic and early
      diastolic SR were also diminished in the obese, whereas no intergroup differences
      existed for the circumferential deformation indexes. LV twist was more pronounced
      in the obese (+1.7 degrees , P < 0.01) on account of greater apical rotation only
      (4.1 +/- 0.9 vs. 5.2 +/- 1.2 degrees , P < 0.01), potentially compensating for
      the loss in longitudinal function. Systolic-diastolic coupling, an important
      component of early filling and diastolic function, was maintained with severe
      obesity. No intergroup differences were reported regarding time to peak values
      for all VVI indexes highlighting that dynamics of strain and twist/untwist along
      the cardiac cycle was preserved with severe obesity. Isolated severe obesity in
      adolescents, at a preclinical stage, is associated with changes in myocardial
      deformation and torsional mechanics that could be in part related to alterations
      in relaxation and contractility properties of subendocardial fibers.

PMID- 22653312
TI  - Adipokines, ghrelin and obesity-associated insulin resistance in nondiabetic
      patients with acute coronary syndrome.
AB  - Altered glucose metabolism negatively modulates outcome in acute coronary
      syndromes (ACS). Insulin resistance is commonly associated with increasing BMI in
      the general population and these associations may involve obesity-related changes
      in circulating ghrelin and adipokines. We aimed at investigating interactions
      between BMI, insulin resistance and ACS and their associations with plasma
      ghrelin and adipokine concentrations. Homeostasis model assessment of insulin
      resistance (HOMA(IR))-insulin resistance index, plasma adiponectin, leptin, total
      (T-Ghrelin), acylated (Acyl-Ghrelin), and desacylated ghrelin (Desacyl-Ghrelin)
      were measured in 60 nondiabetic ACS patients and 44 subjects without ACS matched
      for age, sex, and BMI. Compared with non-ACS, ACS patients had similar HOMA(IR)
      and plasma adipokines, but lower T- and Desacyl-Ghrelin and higher Acyl-Ghrelin.
      Obesity (BMI > 30) was associated with higher HOMA(IR), lower adiponectin, and
      higher leptin (P < 0.05) similarly in ACS and non-ACS subjects. In ACS (n = 60)
      HOMA(IR) remained associated negatively with adiponectin and positively with
      leptin independently of BMI and c-reactive protein (CRP) (P < 0.05). On the other
      hand, low T- and Desacyl-Ghrelin with high Acyl-Ghrelin characterized both obese
      and non-obese ACS patients and were not associated with HOMA(IR). In conclusion,
      in ACS patients, obesity and obesity-related changes in plasma leptin and
      adiponectin are associated with and likely contribute to negatively modulate
      insulin resistance. ACS per se does not however enhance the negative impact of
      obesity on insulin sensitivity. High acylated and low desacylated ghrelin
      characterize ACS patients independently of obesity, but are not associated with
      insulin sensitivity.

PMID- 22653313
TI  - Post-treatment change in the localization of recurrent or persistent macular
      edema secondary to branch retinal vein occlusion.
AB  - PURPOSE: To investigate the change in localization of recurrent or persistent
      macular edema (ME) secondary to branch retinal vein occlusion (BRVO) after a
      therapeutic intervention. METHODS: Twenty-six eyes of 23 patients with recurrent
      or persistent ME secondary to BRVO were included in this retrospective case
      series. We analyzed the distance between the fovea and the top of the ME (fovea
      ME top distance) and the ME area using optical coherence tomography before
      treatment and when ME recurred or persisted. RESULTS: The fovea-ME top distance
      decreased from 1.8 +/- 1.6 to 1.2 +/- 1.3 mm (p = 0.008). The ME area also
      decreased from 11.9 +/- 4.9 to 7.6 +/- 5.0 mm(2) (p = 0.0003). The retinal
      vascular leakage area correlated with the ME area in all eyes. CONCLUSION: The
      site of recurrent or persistent ME tends to shift toward the fovea. These results
      suggest that residual perifoveal vascular leakage might be the predominant cause
      of recurrent or persistent ME.

PMID- 22653314
TI  - The prevalence of primary angle closure glaucoma in European derived populations:
      a systematic review.
AB  - AIM: To estimate the prevalence of primary angle closure glaucoma (PACG) in
      European derived populations. METHOD: Systematic review and modelling of PACG
      prevalence data from population studies. PACG was defined according to the ISGEO
      definition requiring structural and/or functional evidence of glaucomatous optic
      neuropathy. Prevalence estimates were applied to the 2010 United Nations
      projected population figures to estimate case numbers. RESULTS: The prevalence of
      PACG in those 40 years or more is 0.4% (95% CI 0.3% to 0.5%). Age-specific
      prevalence values are 0.02% (CI 0.00 to 0.08) for those 40-49 years, 0.60% (0.27
      to 1.00) for those 50-59 years, 0.20% (0.06 to 0.42) for those 60-69 years and
      0.94% (0.63 to 1.35) for those 70 years and older. Three-quarters of all cases
      occur in female subjects (3.25 female to 1 male; CI 1.76 to 5.94). CONCLUSION:
      This analysis provides a current evidence-based estimate of PACG prevalence in
      European derived populations and suggests there are 130,000 people in the UK,
      1.60 million people in Europe and 581,000 people in the USA with PACG today.
      Accounting for ageing population structures, cases are predicted to increase by
      19% in the UK, 9% in Europe and 18% in the USA within the next decade. PACG is
      more common than previously thought, and all primary glaucoma cases should be
      considered to be PACG until the anterior chamber angle is shown to be open on
      gonioscopy.

PMID- 22653315
TI  - Control issues.

PMID- 22653316
TI  - What lies behind chemotherapy-induced ovarian toxicity?
AB  - Seminal advances in anticancer therapy as well as supportive care strategies have
      led to improved survival rates, posing an emphasis on preserving an optimum
      quality of life after cancer treatment. This recognition has paved the way to an
      increasing research of long-term side effects, both clinical and preclinical and
      to an ongoing design of a supportive care system to evaluate and treat long-term
      adverse effects of anticancer treatments, including the impact on fertility. As
      with many adverse effects induced by anticancer treatments, the literature
      comprised mostly clinical data with regard to chemotherapy-induced
      gonadotoxicity, while understanding of the biological mechanism is lagging. The
      impact of anticancer treatments on female fertility depends on the women's age at
      the time of treatment, the chemotherapy protocol, the duration, and total
      cumulative dose administered. Several suggested mechanisms that underlie
      chemotherapy-induced gonadotoxicity have been described. This review illustrates
      the clinical evidence, as well as its supportive preclinical studies, while
      proceeding from the 'bedside to the bench work' and provides an insight to what
      lies behind chemotherapy-induced gonadotoxicity.

PMID- 22653317
TI  - XIAP: a potential determinant of ovarian follicular fate.
AB  - X-linked inhibitor of apoptosis protein (XIAP), a member of the inhibitor of
      apoptosis protein family, is involved in regulating a number of functions
      including receptor-mediated intracellular signalling and early development. Its
      role as an endogenous caspase inhibitor, however, is the most highly
      characterised. Consequently, this protein has been implicated as an anti
      apoptotic factor in the ovary. In vitro and in vivo studies have begun dissecting
      the stimuli and signalling networks that lead to XIAP upregulation in granulosa
      cells. The objective of this review is to briefly summarise the current knowledge
      concerning XIAP and its interactions with different caspases. Furthermore, XIAP's
      emerging role in the mammalian ovary will be explored and comparison is made with
      its functions in the mammary gland. Finally, the idea that XIAP may act as a
      molecular signalling switch in granulosa cells following detachment from
      underlying layers to promote follicular atresia will be introduced.

PMID- 22653318
TI  - Identification of miRNAs associated with the follicular-luteal transition in the
      ruminant ovary.
AB  - Little is known about the involvement of microRNAs (miRNAs) in the follicular
      luteal transition. The aim of this study was to identify genome-wide changes in
      miRNAs associated with follicular differentiation in sheep. miRNA libraries were
      produced from samples collected at defined stages of the ovine oestrous cycle and
      representing healthy growing follicles, (diameter, 4.0-5.5  mm), pre-ovulatory
      follicles (6.0-7.0  mm), early corpora lutea (day 3 post-oestrus) and late
      corpora lutea (day 9). A total of 189 miRNAs reported in sheep or other species
      and an additional 23 novel miRNAs were identified by sequencing these libraries.
      miR-21, miR-125b, let-7a and let-7b were the most abundant miRNAs overall,
      accounting for 40% of all miRNAs sequenced. Examination of changes in cloning
      frequencies across development identified nine different miRNAs whose expression
      decreased in association with the follicular-luteal transition and eight miRNAs
      whose expression increased during this transition. Expression profiles were
      confirmed by northern analyses, and experimentally validated targets were
      identified using miRTarBase. A majority of the 29 targets identified represented
      genes known to be actively involved in regulating follicular differentiation in
      vivo. Finally, luteinisation of follicular cells in vitro resulted in changes in
      miRNA levels that were consistent with those identified in vivo, and these
      changes were temporally associated with changes in the levels of putative miRNA
      targets in granulosa cells. In conclusion, this is the first study to
      characterise genome-wide miRNA profiles during different stages of follicle and
      luteal development. Our data identify a subset of miRNAs that are potentially
      important regulators of the follicular-luteal transition.

PMID- 22653319
TI  - Differentially expressed plasma microRNAs in premature ovarian failure patients
      and the potential regulatory function of mir-23a in granulosa cell apoptosis.
AB  - Recent studies implicate the regulatory function of microRNAs (miRNAs) in oocyte
      maturation and ovarian follicular development. Differentially expressed miRNAs
      are found in the plasma of premature ovarian failure (POF) patients and normal
      cycling women. In this study, miRNA-regulated signaling pathways and related
      genes were described using Gene Ontology (GO) analysis and Kyoto Encyclopedia of
      Genes and Genomes pathway analysis. The effect of mir-23a on granulosa cell
      apoptosis was also studied by examining the protein expression of X-linked
      inhibitor of apoptosis protein (XIAP) and caspase-3, followed by subsequent
      counting of apoptotic cells after Hoechst 33258 staining. Both GO analysis and
      pathway analysis suggested that many signaling pathways, including the AKT
      signaling pathway, steroid hormone receptor signaling pathways, and others, were
      regulated by this group of differentially expressed miRNAs. A decrease in XIAP
      expression (mRNA and protein level) and caspase-3 protein levels and an increase
      in cleaved caspase-3 protein were observed in human ovarian granulosa cells
      transfected with pre-mir-23a, along with an increased occurrence of apoptosis. In
      conclusion, differentially expressed miRNAs in the plasma of POF patients may
      have regulatory effects on proliferation and apoptosis of granulosa cells by
      affecting different signaling pathways. Mir-23a may play important roles in
      regulating apoptosis via decreasing XIAP expression in human ovarian granulosa
      cells.

PMID- 22653320
TI  - Inflammatory markers and acid-base equilibrium in exhaled breath condensate of
      stable and unstable asthma patients.
AB  - BACKGROUND: Nitrosative and acid stress play an important role in the
      pathogenesis of asthma. The aim of this study was to evaluate whether, in
      asthmatics, a link exists between the concentrations of nitrite/nitrate, ammonia
      and pH values in exhaled breath condensate (EBC) and asthma severity, lung
      function, exhaled nitric oxide (F(ENO)), total IgE, eosinophil cationic protein
      (ECP) and blood eosinophilia. METHODS: The above-mentioned parameters were
      measured in 19 healthy volunteers and 91 allergic asthmatics divided into three
      groups, i.e. 22 subjects with steroid-naive stable asthma, 35 with inhaled
      corticosteroid (ICS)-treated stable asthma and 34 with ICS-treated unstable
      asthma. RESULTS: Compared with healthy subjects, EBC from asthmatics had
      significantly lower pH values and ammonia concentrations and significantly higher
      levels of nitrite/nitrate. The extent of these changes was higher in patients
      with unstable than in patients with steroid-naive and stable ICS-treated asthma.
      The EBC pH was positively correlated with ammonia and negatively correlated with
      nitrite/nitrate, F(ENO) or blood eosinophilia in all three groups of asthmatics.
      Significant positive correlations between EBC nitrite/nitrate and blood
      eosinophilia, ECP levels or F(ENO) were observed in all groups of asthmatics.
      Significant negative correlations between EBC ammonia and nitrite/nitrate,
      F(ENO), ECP concentrations or blood eosinophilia were demonstrated in the groups
      of ICS-naive and ICS-treated stable asthmatics. CONCLUSIONS: In asthmatic
      patients there is a relationship between EBC pH, ammonia and nitrite/nitrate
      concentrations and other recognized markers of airway inflammation. EBC pH
      values, ammonia and nitrite/nitrate levels measured together may help to assess
      airway inflammatory status and asthma severity.

PMID- 22653321
TI  - Serum total bilirubin is inversely associated with brachial-ankle pulse wave
      velocity in men with hypertension.
AB  - Serum total bilirubin has been suggested to have the potential anti-inflammatory
      and antioxidant effects on the vasculature. This study was designed to
      investigate the association of bilirubin with brachial-ankle pulse wave velocity
      (baPWV), a marker of arterial stiffness and cardiovascular disease. Hypertensive
      male subjects (n = 2,361) were classified into groups according to the 50th,
      75th, and 95th percentiles of baPWV value. Correlation and regression analysis
      were used to assess the relationship between baPWV and other variables.
      Hypertensive subjects with baPWV above the 50th, 75th, and 95th percentiles had a
      significantly lower bilirubin level than those with baPWV under them (0.97 +/-
      0.40 vs. 1.00 +/- 0.41 mg/dl, P < 0.001; 0.95 +/- 0.39 vs. 0.99 +/- 0.41 mg/dl, P
      = 0.001; 0.92 +/- 0.36 vs. 0.99 +/- 0.42 mg/dl, P = 0.048, respectively).
      Bilirubin is inversely related to baPWV (R (2) = 0.0032, P = 0.003) and C
      reactive protein (CRP) (correlation coefficient = -0.13, P < 0.001). A 0.1 mg/dl
      increase in bilirubin was associated with a 19, 20, and 34 % reduced odds ratio
      for baPWV above the 50th, 75th, and 95th percentiles, respectively [odds ratio
      (OR) 0.77 (95 % confidence interval (CI) 0.62-0.95), P = 0.015; OR 0.80 (95 % CI
      0.64-0.99), P = 0.044; OR 0.68 (95 % CI 0.45-1.00), P = 0.048, respectively]
      after adjustment for several variables. This study demonstrates an independent
      inverse association between bilirubin and baPWV in hypertensive men.
      Additionally, reduced CRP may be one of mediators on the mechanisms how bilirubin
      reduces baPWV.

PMID- 22653322
TI  - Short- and long-term effects of alkali therapy in chronic kidney disease: a
      systematic review.
AB  - BACKGROUND: Clinical practice guidelines recommend alkali therapy in patients
      with non-dialysis-dependent chronic kidney disease (CKD) and metabolic acidosis
      to prevent complications from metabolic acidosis. We systematically reviewed the
      effect of sodium bicarbonate on benefits and harms in patients with CKD. METHODS:
      We searched for randomized controlled trials in MEDLINE (through July 2011),
      Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and
      scientific abstracts. We included trials that compared sodium bicarbonate to
      standard-of-care therapy or placebo that reported on kidney-related outcomes. We
      performed random-effects model meta-analyses to compute net changes (for
      continuous variables) and risk ratios (for binary variables). RESULTS: Two short
      term (<= 7 days) crossover trials and 4 long-term (>= 2 months) parallel-design
      randomized controlled trials met eligibility (312 patients). All 6 trials
      prescribed sodium bicarbonate in the alkali-treated group. In the long-term
      studies, alkali therapy was associated with a net decrease in serum creatinine (
      0.07 mg/dl, 95% CI -0.09, -0.05; p < 0.001; I(2) = 0), a net improvement in GFR
      (3.2 ml/min/1.73 m(2), 95% CI 1.6, 4.7; p < 0.001; I(2) = 0), and a lower
      incidence of dialysis initiation (risk ratio 0.21, 95% CI 0.08, 0.54; p = 0.001;
      I(2) = 0). No benefit was observed on the serum creatinine or GFR in short-term
      studies. Alkali therapy was not associated with a higher likelihood of initiating
      or escalating anti-hypertensive medications. CONCLUSIONS: Alkali therapy is
      associated with an improvement in kidney function, which may afford a long-term
      benefit in slowing the progression of CKD. However, differences in study
      protocols and small sample sizes preclude definitive conclusions.

PMID- 22653323
TI  - Effect of playing surface properties on neuromuscular fatigue in tennis.
AB  - PURPOSE: The aim of this study was to evaluate the effect of the playing surface
      properties on the development of neuromuscular fatigue in tennis. METHODS: Ten
      subjects played randomly two tennis matches on hard court (HARD) and clay court
      (CLAY) for an effective playing duration of 45 min (i.e., corresponding
      approximately to a 3-h game). Before and after each match, the maximal voluntary
      contraction (MVC) force of the plantar flexors, the maximal voluntary activation
      level, the maximal compound muscle action characteristic, and the EMG activity
      were determined on the soleus (SOL) and lateralis gastrocnemius (LG) muscles.
      Tetanic and single stimulations were also delivered to evaluate the presence of
      low-frequency fatigue and contractile impairment. Finally, reflex responses were
      evoked on the relaxed muscle (H-reflex) and during MVC (H-reflex and V-wave).
      RESULTS: Statistical analysis did not reveal any significant difference between
      playing surfaces. MVC was similarly reduced after the game (HARD, -9.1% +/- 8.7%;
      CLAY, -4.3% +/- 19.9%) and was associated with alterations of the contractile
      properties of the plantar flexor muscles. The implication of central factors was
      less clear, as evidenced by the significant reduction (P < 0.05) of the H-reflex
      on the relaxed LG (HARD, -16.2% +/- 33.3%; CLAY, -23.9% +/- 54.0%) and SOL (HARD,
      -16.1% +/- 48.9%; CLAY, -34.9% +/- 35.9%) and the nonsignificant reduction of the
      activation level. In addition, the reflex responses evoked during MVC were not
      significantly modified by the exercise. CONCLUSION: These results suggest that
      the ground surface properties influence neither the extent nor the origin of
      neuromuscular fatigue in tennis. The moderate force decrement observed in the
      current study was mainly associated with peripheral fatigue.

PMID- 22653325
TI  - Computational fluid dynamics in aneurysm research: critical reflections, future
      directions.

PMID- 22653326
TI  - Individual detection of patients with Parkinson disease using support vector
      machine analysis of diffusion tensor imaging data: initial results.
AB  - BACKGROUND AND PURPOSE: Brain MR imaging is routinely performed in the work-up of
      suspected PD, yet its role is essentially limited to the exclusion of other
      pathologies. We performed a pattern-recognition analysis based on DTI data to
      detect subjects with PD at the individual level. MATERIALS AND METHODS: We
      included 40 consecutive patients with Parkinsonism suggestive of PD who had DTI
      at 3T, brain (123)I ioflupane SPECT (DaTSCAN), and extensive neurologic testing
      including follow-up (17 PD: age range, 67.8 +/- 6.7 years; 9 women; 23 Other:
      consisting of atypical forms of Parkinsonism; age range, 67.2 +/- 9.7 years; 7
      women). Data analysis included group-level TBSS and individual-level SVM
      classification. RESULTS: At the group level, patients with PD versus Other had
      spatially consistent increase in FA and decrease in RD and MD in a bilateral
      network, predominantly in the right frontal white matter. At the individual
      level, SVM correctly classified patients with PD at the individual level with
      accuracies up to 97%. CONCLUSIONS: Support vector machine-based pattern
      recognition of DTI data provides highly accurate detection of patients with PD
      among those with suspected PD at an individual level, which is potentially
      clinically applicable. Because most suspected subjects with PD undergo brain MR
      imaging, already existing MR imaging data may be reused; this practice is very
      cost-efficient.

PMID- 22653327
TI  - Change in biomass of symbiotic ants throughout the ontogeny of a myrmecophyte,
      Macaranga beccariana (Euphorbiaceae).
AB  - Macaranga myrmecophytes (ant-plants) provide their partner symbiotic ants (plant
      ants) with food bodies as their main food, and they are protected by the plant
      ants from herbivores. The amount of resource allocated to food bodies determines
      the plant-ant colony size and consequently determines the intensity of ant
      defense (anti-herbivore defense by plant-ants). As constraints in resource
      allocation change as plants grow, the plant-ant colony size is hypothesized to
      change with the ontogenesis of Macaranga myrmecophyte. To determine the
      ontogenetic change in the relative size of the plant-ant colony, we measured the
      dry weights of the whole plant-ant colony and all of the aboveground parts of
      trees at various ontogenetic stages for a myrmecophytic species (Macaranga
      beccariana) in a Bornean lowland tropical rain forest. Ant biomass increased as
      plant biomass increased. However, the rate of increase gradually declined, and
      the ant biomass appeared to reach a ceiling once trees began to branch. The
      ant/plant biomass ratio consistently decreased as plant biomass increased, with
      the rate of decrease gradually accelerating. We infer that the ontogenetic
      reduction in ant/plant biomass ratio is caused by an ontogenetic change in
      resource allocation to food rewards for ants related to the physiological changes
      accompanying the beginning of branching.

PMID- 22653328
TI  - [Economic impact of infected total hip arthroplasty in the German diagnosis
      related groups system].
AB  - BACKGROUND: The treatment of an infected total hip arthroplasty is becoming an
      increasing economic problem. The additional costs of treatment are insufficiently
      represented in the diagnosis-related groups (DRG) categories. The aim of this
      study was to clarify whether the costs can be covered under the German DRG system
      and to identify the extent of the surplus or negative balance. PATIENTS AND
      METHODS: A retrospective analysis of the treatment costs of total hip
      arthroplasty was carried out. Data from all patients treated at the orthopedic
      clinic of the University Hospital in Rostock were collected from patient records
      and from the hospital information system and calculation of the personnel and
      material costs using data from the central pharmacy and control centre of the
      University of Rostock. RESULTS: In this study a total of 49 patients were
      included. The average treatment costs were 29,331.36 EUR per patient for an
      infected and 6,263.59 EUR for a primarily non-infected total hip arthroplasty. A
      comparison between the calculated and compensated costs resulted in an average
      deficit of 12,685.60 EUR per patient and an average surplus of 781.41 EUR per
      patient in the control group. CONCLUSIONS: An economically viable treatment of
      infected total hip arthroplasty was not possible mostly due to the increased
      personnel and material costs but also to the lack of inclusion of the procedures
      in the DRG system. Further multicenter cost analysis studies and extensive
      quality assurance measures are necessary with respect to a comprehensive medical
      standard for a medically meaningful and economically reasonable treatment of
      periprosthetic infections.

PMID- 22653330
TI  - Unexpected gallbladder cancer after laparoscopic cholecystectomy for acute
      cholecystitis: a worrisome picture.
AB  - OBJECTIVE: The objective of this study is to assess the prognosis of unexpected
      gallbladder cancer diagnosed after laparoscopic cholecystectomy for acute
      cholecystitis. METHODS: Data of all patients treated for unexpected gallbladder
      cancer after laparoscopic cholecystectomy at a tertiary care surgical center
      between January 1998 and December 2009 were reviewed. Demographics and clinical
      and pathological data of patients submitted to adjunctive revisional surgery were
      analyzed. Survival was calculated by the Kaplan-Meier method, and log-rank test
      was used to compare the survival curves. The Cox proportional hazard model was
      used to determine the effect on survival of urgent surgery for acute
      cholecystitis and of the other common factors such as age, gender, tumor grading,
      pT stage, nodal involvement, residual disease at re-exploration, and American
      Joint Committee on Cancer stage. RESULTS: In the considered period, 34 patients
      with pT1b, pT2, or pT3 unexpected gallbladder cancer underwent a second standard
      revisional procedure including resection of liver segments 4b and 5,
      lymphadenectomy, and port-sites excision. Thirteen patients had previously
      undergone urgent surgery for acute cholecystitis; 21 had undergone a routine
      operation. The 5-year overall survival was 63.3 %. At multivariate analysis, G3
      tumor grading (hazard ratio, 12.261; p = 0.002), residual disease at re
      exploration [hazard ratios (HR) = 7.760, p = 0.004], and urgent surgery for acute
      cholecystitis (HR = 5.436, p = 0.012) were independent predictors of poor
      prognosis. CONCLUSIONS: The prognosis of unexpected gallbladder cancer is
      worsened when laparoscopic cholecystectomy is performed for acute cholecystitits.
      The unfavorable impact of emergency surgery on prognosis might be related to
      intraoperative gallbladder emptying with bile spillage and cancer dissemination.

PMID- 22653329
TI  - [Long-term results of Imhauser osteotomy for chronic slipped femoral head
      epiphysiolysis].
AB  - BACKGROUND: The treatment of slipped capital femoral epiphysis (SCFE) has
      produced in its complexity a great deal of discussion. One well-established
      method of operative treatment is the corrective intertrochanteric osteotomy
      according to Imhauser. This study presents the clinical and radiological long
      term results and the biomechanical impacts of this invasive intervention.
      PATIENTS AND METHODS: A total of 28 patients with chronic SCFE with slip angles
      between 30 degrees  and 60 degrees  were treated by Imhauser osteotomy at an
      average age of 13.7 years (SD+/- 2.2 years, range 9-19 years) and were reexamined
      after an average period of 24 years (SD+/- 6.7 years, range 12-32 years).
      RESULTS: The results of the biomechanical analyses indicated an increase of force
      affecting the articulating joint postoperative compared to preoperative, even
      though the pressure on the joint decreased. This can be interpreted as a result
      of the enlargement of the articulating joint surface. Of the patients 17 achieved
      an excellent Harris hip score, 8 a good and 3 a satisfying result in the clinical
      assessment. There were significant differences in the degree of arthrosis between
      the side with and the side without osteotomy. Out of 27 cases 10 showed a
      decrease in the degree of arthrosis of the side with osteotomy whereas 3 cases
      showed an increase. In 14 cases no difference was measured. CONCLUSIONS: Despite
      the valgisation the Imhauser osteotomy relieves the hip joint thus probably
      counteracting degenerative alterations even though being unable to fully prevent
      this progress. The good biomechanical, clinical and radiological results support
      indications for Imhauser osteotomy for slip angles between 30 degrees  and 60
      degrees .

PMID- 22653331
TI  - Outcome of surgery for colovesical and colovaginal fistulas of diverticular
      origin in 40 patients.
AB  - INTRODUCTION: According to literature, colonic resection with a primary
      anastomosis and no defunctioning ileostomy is a safe treatment for colovesical or
      colovaginal fistula of diverticular origin. This study investigates the outcome
      of surgery for this patient group in a regional hospital. METHODS: Patients were
      obtained from a prospective database in the period 2004-2011. Several variables
      were investigated for their relation with surgical outcome. RESULTS: A
      colovesical (n = 35) or colovaginal (n = 5) fistula was diagnosed in 18 men and
      22 women. The mean age was 69 years (range, 45-90). A rectosigmoid resection with
      primary anastomosis was performed in 32 patients. Fourteen patients received a
      defunctioning ileostomy. Eight patients were treated with a Hartmann procedure.
      Overall 30-day treatment-related morbidity and mortality was 48 and 8 %,
      respectively. Major morbidity, because of anastomotic leakage, was mainly
      observed in the primary anastomosis group without a defunctioning ileostomy.
      Morbidity and mortality were associated with high body mass index, diabetes, use
      of corticosteroids, and American Society of Anesthesiologists classification,
      though not significantly. CONCLUSIONS: One should be liberal in the use of a
      defunctioning ileostomy in case of a primary anastomosis after colonic resection
      for a diverticular fistula, in order to prevent high morbidity rates due to
      anastomotic leakage.

PMID- 22653332
TI  - A 1D Schiff base zinc polymer as a versatile metallo-ligand for the synthesis of
      polynuclear zinc cages.
AB  - The 1D polymeric Schiff base zinc complex, [LZn(2)Et(2)](n), where LH(2) = (NN'
      ethylene-bis(4-iminopentan-2-one)) has been demonstrated as a useful synthetic
      metallo building block for the synthesis of homo and heteronuclear zinc cages.
      The reaction of [LZn(2)Et(2)](n) with CdI(2) afforded the hetero-nuclear cage, 1,
      [L(2)Zn(4)(Et)(2)CdI(4)], while reaction with HgI(2) afforded a hexanuclear zinc
      cage, [L(2)Zn(6)(Et)(4)(MU(4)O)(MU(3)OEt)I], 2. The versatility of
      [LZn(2)Et(2)](n) as a metallo building block is demonstrated through the reaction
      with ferrocenyl carboxylic acid, affording the ferrocenyl supported zinc cage,
      [L(2)Zn(8)(FcCO(2))(4)(Et)(2)(OEt)(2)(MU(4)O)(2)], 3, while the reaction with
      Er(III) acetate afforded the decanuclear zinc cage,
      [L(3)Zn(10)(MU(4)O)(4)(Et)(6)], 4.

PMID- 22653333
TI  - Psychometric properties of a Russian version of the General Health Questionnaire
      28.
AB  - BACKGROUND: The 28-item General Health Questionnaire (GHQ-28) is a scaled version
      of the General Health Questionnaire that has been used internationally to screen
      for mental disorders in nonpsychiatric populations. There is great need to
      validate international screening instruments in the Russian language for their
      use in post-Soviet countries. METHODS: 200 persons were surveyed in a deprived
      area of Almaty, Kazakhstan using the Russian version of the GHQ-28 and
      socioeconomic measures (income level, employment situation and education). We
      calculated the median and the mean GHQ-28 scores for different socioeconomic
      subgroups. The internal reliability was tested using Cronbach's alpha coefficient
      and intersubscale correlations. We conducted an exploratory factor analysis using
      varimax rotation. RESULTS: The median score of the GHQ-28 was 2 (mean = 3.56; SD
      = 5.09) for the total sample. Higher age, unemployment and female gender were
      significantly associated with high mean GHQ-28 scores. Cronbach's alpha
      coefficient was 0.92 for the total scale. Exploratory factor analysis revealed
      four factors explaining 50.07% of the variance. The factor Anxiety/Insomnia
      accounted for 14.87%, Severe Depression for 13.74%, Social Dysfunction for 13.47%
      and Somatic Symptoms for 8.81% of the variance. CONCLUSIONS: The test showed good
      internal consistency. The median GHQ-28 score was relatively low compared to
      other countries. The subscale Severe Depression including items on suicidal
      ideation may have a lower acceptance than the other subscales Somatic Symptoms,
      Anxiety/Insomnia and Social Dysfunction.

PMID- 22653334
TI  - RAS/ERK pathway transcriptional regulation through ETS/AP-1 binding sites.
AB  - The RAS/RAF/MEK/ERK signaling pathway is activated by mutation in many cancers.
      Neighboring ETS and AP-1 DNA binding sequences can act as response elements for
      transcriptional activation by this pathway. ERK phosphorylation of an ETS
      transcription factor is one mechanism of activating the RAS/ERK gene expression
      program that can promote cancer cell phenotypes such as proliferation, invasion,
      and metastasis. Recent genome-wide mapping of ETS proteins over-expressed by
      chromosomal rearrangement in prostate cancer reveals a second mechanism for
      activation of this gene expression program. An oncogenic subset of ETS
      transcription factors can activate RAS/ERK target genes even in the absence of
      RAS/ERK pathway activation by binding ETS/AP-1 sequences. Thus, regulation of
      cancer cell invasion and metastasis via ETS/AP-1 sequence elements depends on
      which ETS protein is bound, and the status of the RAS/ERK pathway. This
      commentary will focus on what is known about the selectivity of ETS/AP-1
      sequences for different ETS transcription factors and the transcriptional
      consequences of ETS protein selection.

PMID- 22653336
TI  - Synthesis, spectroscopic analysis and photolabilization of water-soluble
      ruthenium(III)-nitrosyl complexes.
AB  - In this paper, the synthesis, structural and spectroscopic characterization of a
      series of new Ru(III)-nitrosyls of {RuNO}(6) type with the coligand TPA (tris(2
      pyridylmethyl)amine) are presented. The complex [Ru(TPA)Cl(2)(NO)]ClO(4) (2) was
      prepared from the Ru(III) precursor [Ru(TPA)Cl(2)]ClO(4) (1) by simple reaction
      with NO gas. This led to the surprising displacement of one of the pyridine (py)
      arms of TPA by NO (instead of the substitution of a chloride anion by NO), as
      confirmed by X-ray crystallography. NO complexes where TPA serves as a
      tetradentate ligand were obtained by reacting the new Ru(II) precursor
      [Ru(TPA)(NO(2))(2)] (3) with a strong acid. This leads to the dehydration of
      nitrite to NO(+), and the formation of the {RuNO}(6) complex
      [Ru(TPA)(ONO)(NO)](PF(6))(2) (4), which was also structurally characterized.
      Derivatives of 4 where nitrite is replaced by urea (5) or water (6) were also
      obtained. The nitrosyl complexes obtained this way were then further investigated
      using IR and FT-Raman spectroscopy. Complex 2 with the two anionic chloride
      coligands shows the lowest N-O and highest Ru-NO stretching frequencies of 1903
      and 619 cm(-1) of all the complexes investigated here. Complexes 5 and 6 where
      TPA serves as a tetradentate ligand show nu(N-O) at higher energy, 1930 and 1917
      cm(-1), respectively, and nu(Ru-NO) at lower energy, 577 and 579 cm(-1),
      respectively, compared to 2. These vibrational energies, as well as the inverse
      correlation of nu(N-O) and nu(Ru-NO) observed along this series of complexes,
      again support the Ru(II)-NO(+) type electronic structure previously proposed for
      {RuNO}(6) complexes. Finally, we investigated the photolability of the Ru-NO bond
      upon irradiation with UV light to determine the quantum yields (phi) for NO
      photorelease in complexes 2, 4, 5, and additional water-soluble complexes
      [Ru(H(2)edta)(Cl)(NO)] (7) and [Ru(Hedta)(NO)] (8). Although {RuNO}(6) complexes
      are frequently proposed as NO delivery agents in vivo, studies that investigate
      how phi is affected by the solvent water are lacking. Our results indicate that
      neutral water is not a solvent that promotes the photodissociation of NO, which
      would present a major obstacle to the goal of designing {RuNO}(6) complexes as
      photolabile NO delivery agents in vivo.

PMID- 22653335
TI  - Expert review document part 2: methodology, terminology and clinical applications
      of optical coherence tomography for the assessment of interventional procedures.

PMID- 22653337
TI  - Effect of growth differentiation factor 5 on the proliferation and tenogenic
      differentiation potential of human mesenchymal stem cells in vitro.
AB  - The use of growth differentiation factor 5 (GDF-5) in damaged tendons has been
      shown to improve tendon repair. It has been hypothesized that further
      improvements may be achieved when GDF-5 is used to promote cell proliferation and
      induce tenogenic differentiation in human bone marrow-derived mesenchymal stem
      cells (hMSCs). However, the optimal conditions required to produce these effects
      on hMSCs have not been demonstrated in previous studies. A study to determine
      cell proliferation and tenogenic differentiation in hMSCs exposed to different
      concentrations of GDF-5 (0, 5, 25, 50, 100 and 500 ng/ml) was thus conducted. No
      significant changes were observed in the cell proliferation rate in hMSCs treated
      at different concentrations of GDF-5. GDF-5 appeared to induce tenogenic
      differentiation at 100 ng/ml, as reflected by (1) a significant increase in total
      collagen expression, similar to that of the primary native human tenocyte
      culture; (2) a significant upregulation in candidate tenogenic marker gene
      expression, i.e. scleraxis, tenascin-C and type-I collagen; (3) the ratio of type
      I collagen to type-III collagen expression was elevated to levels similar to that
      of human tenocyte cultures, and (4) a significant downregulation of the non
      tenogenic marker genes runt-related transcription factor 2 and sex determining
      region Y (SRY)-box 9 at day 7 of GDF-5 induction, further excluding hMSC
      differentiation into other lineages. In conclusion, GDF-5 does not alter the
      proliferation rates of hMSCs, but, instead, induces an optimal tenogenic
      differentiation response at 100 ng/ml.

PMID- 22653338
TI  - Let's huddle to prevent a muddle: centrosome declustering as an attractive
      anticancer strategy.
AB  - Nearly a century ago, cell biologists postulated that the chromosomal aberrations
      blighting cancer cells might be caused by a mysterious organelle-the centrosome
      that had only just been discovered. For years, however, this enigmatic structure
      was neglected in oncologic investigations and has only recently reemerged as a
      key suspect in tumorigenesis. A majority of cancer cells, unlike healthy cells,
      possess an amplified centrosome complement, which they manage to coalesce neatly
      at two spindle poles during mitosis. This clustering mechanism permits the cell
      to form a pseudo-bipolar mitotic spindle for segregation of sister chromatids. On
      rare occasions this mechanism fails, resulting in declustered centrosomes and the
      assembly of a multipolar spindle. Spindle multipolarity consigns the cell to an
      almost certain fate of mitotic arrest or death. The catastrophic nature of
      multipolarity has attracted efforts to develop drugs that can induce declustering
      in cancer cells. Such chemotherapeutics would theoretically spare healthy cells,
      whose normal centrosome complement should preclude multipolar spindle formation.
      In search of the 'Holy Grail' of nontoxic, cancer cell-selective, and superiorly
      efficacious chemotherapy, research is underway to elucidate the underpinnings of
      centrosome clustering mechanisms. Here, we detail the progress made towards that
      end, highlighting seminal work and suggesting directions for future research,
      aimed at demystifying this riddling cellular tactic and exploiting it for
      chemotherapeutic purposes. We also propose a model to highlight the integral role
      of microtubule dynamicity and the delicate balance of forces on which cancer
      cells rely for effective centrosome clustering. Finally, we provide insights
      regarding how perturbation of this balance may pave an inroad for inducing lethal
      centrosome dispersal and death selectively in cancer cells.

PMID- 22653339
TI  - C/EBP homologous protein contributes to cytokine-induced pro-inflammatory
      responses and apoptosis in beta-cells.
AB  - Induction of the C/EBP homologous protein (CHOP) is considered a key event for
      endoplasmic reticulum (ER) stress-mediated apoptosis. Type 1 diabetes (T1D) is
      characterized by an autoimmune destruction of the pancreatic beta-cells. Pro
      inflammatory cytokines are early mediators of beta-cell death in T1D. Cytokines
      induce ER stress and CHOP overexpression in beta-cells, but the role for CHOP
      overexpression in cytokine-induced beta-cell apoptosis remains controversial. We
      presently observed that CHOP knockdown (KD) prevents cytokine-mediated
      degradation of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and myeloid
      cell leukemia sequence 1 (Mcl-1), thereby decreasing the cleavage of executioner
      caspases 9 and 3, and apoptosis. Nuclear factor-kappaB (NF-kappaB) is a crucial
      transcription factor regulating beta-cell apoptosis and inflammation. CHOP KD
      resulted in reduced cytokine-induced NF-kappaB activity and expression of key NF
      kappaB target genes involved in apoptosis and inflammation, including iNOS, FAS,
      IRF-7, IL-15, CCL5 and CXCL10. This was due to decreased IkappaB degradation and
      p65 translocation to the nucleus. The present data suggest that CHOP has a dual
      role in promoting beta-cell death: (1) CHOP directly contributes to cytokine
      induced beta-cell apoptosis by promoting cytokine-induced mitochondrial pathways
      of apoptosis; and (2) by supporting the NF-kappaB activation and subsequent
      cytokine/chemokine expression, CHOP may contribute to apoptosis and the chemo
      attraction of mononuclear cells to the islets during insulitis.

PMID- 22653340
TI  - The role of ALFY in selective autophagy.
AB  - Autophagy, a highly conserved lysosomal degradation pathway, was initially
      characterized as a bulk degradation system induced in response to starvation. In
      recent years, autophagy has emerged also as a highly selective pathway, targeting
      various cargoes such as aggregated proteins and damaged organelles for
      degradation. The key factors involved in selective autophagy are autophagy
      receptors and adaptor proteins, which connect the cargo to the core autophagy
      machinery. In this review, we discuss the current knowledge about the only
      mammalian adaptor protein identified thus far, autophagy-linked FYVE protein
      (ALFY). ALFY is a large, scaffolding, multidomain protein implicated in the
      selective degradation of ubiquitinated protein aggregates by autophagy. We also
      comment on the possible role of ALFY in the context of disease.

PMID- 22653341
TI  - Endocervical-type mucinous borderline tumors are related to endometrioid tumors
      based on mutation and loss of expression of ARID1A.
AB  - Nongastrointestinal-type mucinous borderline tumors have been described as
      displaying endocervical and serous differentiation and hence have been termed
      "endocervical-type" mucinous borderline tumors, "mixed-epithelial papillary
      cystadenoma of borderline malignancy of mullerian type," or "atypical
      proliferative seromucinous tumors." A striking feature of these tumors is their
      frequent association with endometriosis, which has been reported in a third to a
      half of cases. This is an unusual finding, as pure endocervical and serous tumors
      are not usually associated with endometriosis. ARID1A is a recently identified
      tumor suppressor, which frequently loses its expression and is mutated in
      endometrium-related carcinomas including ovarian clear cell, ovarian
      endometrioid, and uterine endometrioid carcinomas. Although ARID1A mutations and
      their expression have been studied in gynecologic cancer, the expression pattern
      of ARID1A has not been investigated in ovarian atypical proliferative
      (borderline) tumors. In this study, we analyzed ARID1A expression in serous,
      gastrointestinal-type and endocervical-type (seromucinous) mucinous, and
      endometrioid atypical proliferative (borderline) tumors using
      immunohistochemistry and performed mutational analysis in selected cases. We
      observed loss of ARID1A staining in 8 (33%) of 24 seromucinous tumors. In
      contrast, ARID1A staining was retained in all the other 32 tumors except in 1
      endometrioid tumor (P<0.01). Mutational analysis was performed on 2
      representative seromucinous tumors, which showed complete loss of ARID1A. Both
      tumors harbored somatic inactivating ARID1A mutations. Previous studies have
      reported loss of expression and/or mutation of ARID1A in 30% to 57% of
      endometrioid and clear cell carcinomas but only rarely in serous tumors. In
      summary, these tumors often contain endocervical-type mucinous epithelium, but
      they typically display papillary architecture, unlike most endocervical
      neoplasms, and their immunophenotype is different from both endocervical and
      serous tumors. Moreover, they frequently contain ciliated cells, endometrial-type
      cells, cells with abundant eosinophilic cytoplasm, and hobnail-shaped cells, all
      of which can be found in endometrioid tumors. The loss of expression of ARID1A
      and the presence of inactivating mutations of the ARID1A gene further link this
      tumor to endometrioid and clear cell tumors, as does the frequent association
      with endometriosis. Accordingly, we suggest designating these tumors "atypical
      proliferative (borderline) papillary mullerian tumors" as this designation more
      accurately reflects their clinicopathologic, immunohistochemical, and molecular
      genetic features.

PMID- 22653342
TI  - The dichotomy in the histogenesis of endometriosis-associated ovarian cancer:
      clear cell-type versus endometrioid-type adenocarcinoma.
AB  - The histogenesis of endometriosis and endometriosis-associated ovarian cancer is
      one of the most mysterious aspects of pathology. To better understand the
      histogenesis of endometriosis and endometriosis-associated ovarian cancer, we
      analyzed the possibility of a link of endometrium, ovarian surface epithelium,
      and a cortical inclusion cyst to ovarian endometriosis and endometriosis
      associated ovarian cancer by immunohistochemistry using the epithelial membrane
      antigen (an epithelial marker), calretinin (a mesothelial marker), and hepatocyte
      nuclear factor (HNF)-1beta (a clear cell carcinoma-specific transcription
      factor). During ovarian surface epithelium invagination, cortical inclusion cyst
      epithelial cells may, in some cases, undergo mesothelial-epithelial transition
      and subsequently differentiate into endometriosis. This case of endometriosis
      that has undergone Mullerian metaplasia arises from the HNF-1beta-negative cells.
      The remaining endometriosis may develop from the late secretory and menstrual
      endometria, with HNF-1beta-positive staining, by retrograde menstruation.
      Endometrioid adenocarcinoma and clear cell carcinoma arise from the HNF-1beta
      negative and HNF-1beta-positive epithelial cells of endometriosis, respectively.
      It has been proposed that clear cell and endometrioid-type adenocarcinomas arise
      from distinct types of endometriosis with different cells of origin.

PMID- 22653343
TI  - Metastatic mucinous carcinomas in the ovary:  a practical approach to diagnosis
      related to gross aspects and to immunohistochemical evaluation.
AB  - Ovarian mucinous carcinomas are uncommon, and the differential diagnosis is
      metastatic carcinoma mainly from the gastrointestinal tract. The aim was to
      verify the importance of immunohistochemical reactions and the algorithm
      described in literature on the basis of laterality and tumor size. Twenty-five
      cases identified as metastatic mucinous adenocarcinomas were reviewed, along with
      clinical records; a tissue microarray was created, and immunohistochemical
      reactions for CK7, CK20, Ca125, hormonal receptors, WT1, DPC4, beta-catenin, and
      Cdx2 were determined. The median age was 51, and only 9 patients had a history of
      cancer. Sixteen patients (64%) had bilateral tumors, with sizes ranging from 5 to
      36 cm (average, 20.5 cm); 9 (36%) had unilateral tumors varying from 5.5 to 38 cm
      (average, 21.8 cm). Algorithm agreement was 76%; most unilateral tumors were >13
      cm. Common positive markers were Dpc4 (88%), Cdx2 (68%), CK20 (60%), and CK7
      (44%). The useful markers were CK7, CK20, and Cdx2, although there were cases
      with overlapping results. The most common primary tumor was of colorectal origin
      (14 cases). The mean survival age was 32.6 mo. Although the proposed algorithm
      and immunohistochemical reactions are useful tools for diagnosis, some mucinous
      tumors cannot be definitively classified as primary or metastatic without further
      clinical evaluation, emphasizing the limits of this challenging diagnosis.

PMID- 22653344
TI  - Replication protein A in nonearly ovarian adenocarcinomas: correlation with MCM
      2, MCM-5, Ki-67 index and prognostic significance.
AB  - Replication protein A (RPA) is an ssDNA-binding protein required for the
      initiation of DNA replication and the stabilization of ssDNA. Collaboration with
      several molecules, that is, the MCM2-7 complex, has been suggested to be
      imperative for its multifaceted role. In this study, we investigated the
      immunohistochemical expression of the RPA2 subunit in correlation with the MCM-2
      and MCM-5 and Ki67 index, and assessed its prognostic significance in 76 patients
      with nonearly ovarian adenocarcinomas, the majority of whom had a serous
      histotype. RPA2 protein expression was observed in all cases, whereas the
      staining intensity varied from weak to strong. RPA2 expression was correlated
      with the tumor stage in the entire cohort and in serous tumors (P=0.0053 in both
      relationships). Moreover, RPA2 immunoexpression was positively correlated with
      MCM-2 (P=0.0001) and MCM-5 (P<0.0001) expression, but was unrelated to the Ki67
      index (P>0.10). In multivariate survival analysis, RPA2 expression emerged as an
      independent predictor of adverse outcome (P<0.0001) along with tumor histologic
      grade. RPA2 remained an independent predictor of survival (P=0.002) even after
      adjustment for MCM-2 and MCM-5 expression and when analysis was restricted to
      serous carcinomas (P=0.004). Our results further support the interrelation of
      RPA2 protein with MCM-2 and MCM-5 in OCs. Moreover, RPA2 protein may play an
      important role in ovarian tumorigenesis, and may serve as a useful independent
      molecular marker for stratifying patients with OC in terms of prognosis.

PMID- 22653345
TI  - Chromosomal aberrations detected by chromogenic in situ hybridization in
      abdominal wall endometriosis after cesarean section.
AB  - The goal of this study is to evaluate the chromosomal loss in abdominal wall
      endometriosis by chromogenic in situ hybridization (CISH). Twenty-four cases of
      abdominal wall endometriosis that developed after cesarean section at the Korea
      University Medical Center between January 1997 and December 2006 were selected.
      CISH was performed in the sections of tissue microarray block using the Zymed
      CISH centromeric probes for chromosomes 3, 7, 8, 9, 10, 11, 17, and 18. Monosomy
      was defined when the percentage of the nuclei with a single dot was more than
      mean+3 SD of the respective probe in normal control endometrium. CISH study was
      possible in more than half of the endometriosis samples, except for chromosome 9,
      and was most successful for chromosome 17. The frequency of monosomy was high for
      chromosomes 9 (75.0%) and 17 (73.9%), moderate for chromosomes 10 (57.1%) and 18
      (56.3%), and low for chromosomes 3 (12.5%), 7 (22.2%), 8 (10.5%), and 11 (10.5%).
      Monosomy for >2 and 3 chromosomes occurred in 66.7% and 42.9% of the cases,
      respectively. It is concluded that CISH method may be considered a useful
      laboratory technique in detecting chromosomal loss, and multiple chromosomal loss
      is involved in the formation of ectopic endometrium in abdominal wall
      endometriosis.

PMID- 22653346
TI  - Combined ovarian granulosa cell tumor and mucinous tumor:  collision tumor or
      heterologous differentiation?

PMID- 22653347
TI  - Low-grade, low-stage endometrioid endometrial adenocarcinoma: a clinicopathologic
      analysis of 324 cases focusing on frequency and pattern of myoinvasion.
AB  - Patients with low-stage, low-grade endometrial adenocarcinomas have a favorable
      prognosis; however, a subset has a risk of recurrence and death. We were
      interested in evaluating patterns of myometrial invasion and correlating them
      with clinical outcome to potentially identify patients at increased risk. A total
      of 324 cases of low-stage Grade 1 endometrial adenocarcinoma were reviewed to
      identify those with myoinvasion. The myoinvasive cases were classified on the
      basis of the pattern of invasion: infiltrating glands, microcystic elongated and
      fragmented (MELF; a distinctive histologic variant of the infiltrative gland
      pattern), broad front, adenomyosis like, and adenoma malignum. Depth of invasion
      and lymphovascular invasion were recorded, and a clinical follow-up of at least 2
      y was obtained, as most recurrences occur in this time frame. Ninety-eight of 324
      (30%) cases were invasive; 75 had >2 y of follow-up, with an average length of
      follow-up of >7 y (range, 24-154 mo; mean 87 mo). All patients had a hysterectomy
      and bilateral salpingo-oophorectomy; 39 (52%) also underwent a lymphadenectomy.
      Twenty-seven (36%) were superficially invasive (<10% myoinvasion), 42 (56%)
      invaded 10% to 49%, and 6 (8%) invaded >50%. Six (8%) cases exhibited cervical
      stromal invasion (Stage II); the rest were Stage I (65 IA, 4 IB). The invasive
      patterns consisted of infiltrative glands (48; 65%), a broad front (16; 21%),
      MELF (5; 7%), adenomyosis like (5; 7%), and adenoma malignum like (1, 1%). There
      were 65 Stage 1A cases and, of these, the myoinvasive pattern was as follows: 41
      infiltrating glands, 15 broad front, 5 MELF, and 4 adenomyosis like. There were 4
      Stage IB cases, of which 2 had infiltrating glands, 1 had adenoma malignum, and 1
      displayed adenomyosis-like invasion. Six (8%) cases had cervical stromal invasion
      (Stage II), of which 5 had an infiltrative pattern of growth and 1 displayed a
      broad front. Lymphovascular invasion was noted in 6 cases (8%), all of which had
      infiltrative glands. The majority of Grade 1 endometrioid endometrial
      adenocarcinomas do not invade the myometrium. In cases with invasion, the
      infiltrative gland pattern was associated with higher stage, (3/4 Stage IB, 5/6
      Stage II), lymphovascular invasion (4/6 cases), and recurrence (2/75 cases),
      suggesting that this growth pattern may be associated with tumors having other
      histologic features typically associated with more aggressive behavior.

PMID- 22653348
TI  - Why do women with double primary carcinoma of the endometrium and ovary have a
      favorable prognosis?
AB  - Patients with double primary cancer (DPC) of the ovary and endometrium are
      considered to have a better prognosis than patients with only epithelial ovarian
      cancer (EOC). The aim of this study was to clarify the difference in prognosis by
      comparing clinicopathologic characteristics and survival. From the population
      based database of the nationwide Netherlands Cancer Registry, women diagnosed
      between 1996 and 2006 with EOC were identified. Within this database of all EOC
      patients in 11 hospitals, the DPC patients were identified. Differences in
      characteristics between EOC-only and DPC patients were tested using Pearson chi
      tests and t-tests. Differences in overall survival were analyzed by Kaplan-Meier
      survival analyses and log-rank tests. Multivariable Cox regression analyses were
      performed to study the factors that influence survival. Among 1105 EOC patients,
      29 (2.6%) DPC patients were identified. DPC patients were more often
      premenopausal (P<0.01), in the early stage of disease (P<0.01), and more often
      had low-grade endometrioid tumors. Overall survival was better for DPC patients
      (P=0.004), but after stratification for stage the overall survival was similar.
      In multivariable analysis, DPC patients did not show a favorable prognosis after
      adjustment for age, disease stage, histology, tumor grade, and residual tumor
      after surgery. DPC patients seem to constitute a prognostically favorable group
      among EOC patients; however, after correction for age, stage, histology, tumor
      grade, and residue, survival is similar. This study shows how important it is for
      clinicians to distinguish DPC from metastatic diseases.

PMID- 22653349
TI  - Expression levels of adiponectin receptors are decreased in human endometrial
      adenocarcinoma tissues.
AB  - Adiponectin is a cytokine secreted by adipocytes, whose plasma levels are
      decreased in obesity. Adiponectin has insulin-sensitizing, antiatherogenic, and
      antidiabetogenic effects. It has been shown that adiponectin may also exert
      antineoplastic activity through suppression of tumor proliferation and
      neoangiogenesis and through induction of apoptosis. Recently, low adiponectin
      serum concentration has been found in obesity-related malignancies, including
      endometrial cancer. In addition, the expression of adiponectin receptors (AdipoR1
      and AdipoR2) has been documented in several human cancer tissues, but the
      expression has previously not been assessed in human endometrial cancer tissues.
      In this study, we analyzed the immunohistochemical expression of AdipoR1 and
      AdipoR2 in a series of surgically resected human endometrioid adenocarcinoma
      tissues from a total of 141 cases. Decreased AdipoR1 or AdipoR2 expression was
      significantly associated with histological higher grade (P=0.0026 and 0.0004,
      respectively). Decreased expression of AdipoR1 was associated with myometrial
      invasion and lymph node metastasis of endometrioid adenocarcinoma (P=0.0039 and
      P=0.0069, respectively). AdipoR1 and AdipoR2 immunoexpression was significantly
      associated with the expression of the progesterone receptor, although it was not
      significantly correlated with the expression of the estrogen receptor, Ki-67 or
      p53. Our present study raises the possibility that decreased expression of
      adiponectin receptors is implicated in the development, invasion, and metastasis
      of human endometrioid adenocarcinoma. Our findings, moreover, indicate that
      adiponectin receptors could be considered as therapeutic targets for endometrioid
      adenocarcinoma. In adiponectin receptor-positive endometrioid adenocarcinoma, we
      think adiponectin-based anticancer therapy is useful; however, in histological
      high-grade endometrioid adenocarcinoma, in which the expression levels of
      adiponectin receptors are relatively low, adiponectin therapy supported by
      adiponectin receptor induction is needed.

PMID- 22653350
TI  - Uterine lipoleiomyosarcoma:  report of 2 cases and review of the literature.
AB  - Uterine lipoleiomyosarcoma is a rare entity with only 6 case reports in the
      Pubmed database at the time of writing this article. We report 2 additional cases
      of uterine lipoleiomyosarcoma, characterized on microscopy by coexistence of
      leiomyosarcomatous and liposarcomatous components, with focal intermingling,
      without an intervening lipoleiomyomatous area. The liposarcomatous component in
      both of our cases had the morphology of myxoid liposarcoma. Both cases underwent
      postoperative chemotherapy. One of our cases had recurrence in the pelvis with
      microscopic features of myxoid liposarcoma. This patient died with multiple
      metastases 4.5 yr after hysterectomy, with the metastatic lesions being
      liposarcomas, without an evident leiomyosarcomatous component. Although lacking a
      treatment protocol because of the rarity of such cases, postoperative adjuvant
      therapy is mandatory.

PMID- 22653351
TI  - Molecular genetic analysis of nongestational choriocarcinoma in a postmenopausal
      woman:  a case report and literature review.
AB  - Choriocarcinoma is a highly malignant tumor of trophoblastic origin. Most cases
      occur in association with preceding gestational events. However, on very rare
      occasions, nongestational choriocarcinoma arises from germ cell or trophoblastic
      differentiation in different types of carcinoma. This article reports the case of
      a 58-year-old woman with primary nongestational choriocarcinoma of the uterus
      that developed 19 years after her final pregnancy and 4 years after menopause. A
      total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed.
      Histopathological examination showed choriocarcinoma of the uterus without
      components of other germ cell tumors. Karyotype analysis of the tumor cells
      demonstrated XX. We confirmed its nongestational origin by DNA polymorphism
      analysis at 15 short tandem repeat loci. After surgery, the patient was given
      four courses of combination chemotherapy. She is still alive and there has been
      no evidence of recurrence 3 years after surgery.

PMID- 22653352
TI  - Desmoplastic stromal response as defined by positive alpha-smooth muscle actin
      staining is predictive of invasion in adenocarcinoma of the uterine cervix.
AB  - The objective of this research was to examine the immunohistochemical profiles of
      adenocarcinoma in situ (AIS) and early invasive adenocarcinoma (AC) to identify
      biomarkers that enhance the accurate diagnosis of early invasive glandular
      lesions of the cervix. The University of California, Irvine, and Long Beach
      Memorial tumor registries were used to identify 20 women with AIS or early AC
      treated between 1990 and 2008. An immunohistochemical study was performed, and
      the primary endpoint measured was the correlation between biomarker expression
      and invasive disease as diagnosed on hematoxylin and eosin examination. The
      biomarkers studied included alpha-smooth muscle actin (alpha-SMA), estrogen
      receptor, carcinoembryonic antigen, Ki67, p16, cyclooxygenase-2, and cluster of
      differentiation 1a. Stains were described on the basis of (1) positive or
      negative staining; (2) intensity; (3) percentage of positive cells; and (4)
      pattern of staining. Statistical analysis was performed using SYSTAT v. 11.0.
      Fisher exact test, Mann-Whitney nonparametric test, kappa statistic, and
      intraclass correlation coefficient were used to evaluate results and interpreter
      agreement. A statistically significant increase in the staining of the
      periglandular stroma for alpha-SMA was seen in AC as compared with AIS. The
      intensity was 2.2 versus 1.2 (P=0.04) and the percent of positive-staining cells
      was 44% versus 18% (P=0.05) in AC and AIS, respectively. The presence of a
      desmoplastic stromal response as identified by the increased periglandular
      staining for alpha-SMA is useful in identifying invasive glandular lesions of the
      endocervix. Further studies are necessary to establish biologically relevant cut
      off values for alpha-SMA staining.

PMID- 22653353
TI  - Endocervical margin involvement as an important risk factor for abnormal cytology
      after LLETZ.
AB  - This study was designed to determine the risk factors for abnormal Papanicolaou
      (Pap) smear after large loop excision of the transformation zone (LLETZ). We
      retrospectively reviewed the medical records of 343 women who underwent LLETZ
      between 2006 and 2008. The associations between clinicopathologic characteristics
      including margin status and abnormal follow-up cytology were analyzed. Forty-two
      (12.2%) women were found to have abnormal Pap after LLETZ. Old age at the time of
      procedure (21.2% versus 10.1%, P=0.020) and endocervical resection margin
      involvement (33.3% versus 10.7%, P=0.004) were the risk factors for abnormal Pap
      after LLETZ. The histologic grades of LLETZ pathology were inversely correlated
      with abnormal follow-up cytology (P=0.018). Logistic regression analysis revealed
      that old age, endocervical margin involvement, and lower histologic grades of
      LLETZ pathology were independent risk factors for recurrence. Our findings show
      that a positive endocervical margin is an important risk factor for abnormal Pap
      after LLETZ, suggesting that women with positive exocervical or deep cervical
      margins could be followed up with reassurance.

PMID- 22653354
TI  - Conization of the uterine cervix: does the level of gynecologist's training
      predict margin status?
AB  - The management of cervical intraepithelial neoplasia is becoming more
      individualized. The European Federation of Colposcopy has developed guidelines
      for quality assurance and also certifies specialists. The status of the resection
      margins of conization specimens is prognostically important and is a quality
      feature. We examined the rate of positive margins in conization specimens
      according to the training level of the gynecologic surgeon. We reviewed the
      hospital charts of 411 consecutive patients who underwent conization for cervical
      intraepithelial neoplasia or adenocarcinoma in situ between November 2006 and
      December 2009. Preoperative colposcopy was performed to localize and characterize
      the transformation zone and the lesion in all cases. Ninety-seven conizations
      were performed by residents, 138 by staff members, and 124 by 1 certified
      specialist for colposcopy. A total of 334 cold-knife conizations and 25 loop
      electrosurgical excision procedures were carried out. The rates of positive
      histologic margins in conization specimens were 16%, 22%, and 5% for residents,
      staff members, and the certified specialist, respectively (P<0.001). Expertise of
      the gynecologic surgeon in performing conization procedures appears to influence
      the rate of involved margins after conization. These data support quality-assured
      preoperative colposcopy and European Federation of Colposcopy quality assurance
      criteria. Specialization of gynecologic staff members in the field of colposcopy
      is warranted.

PMID- 22653355
TI  - Embryonal (botryoides) rhabdomyosarcoma of the uterus harboring a primitive
      neuroectodermal tumor component.
AB  - The association of a uterine sarcoma botryoides of the adolescence with a
      primitive neuroectodermal tumor is reported in a 12-year-old patient who
      presented with abnormal vaginal bleeding that occurred after passing per vaginam
      a polypoid mass. The sarcoma botryoides of the adolescence exhibited foci of
      cartilage and a central area of primitive neuroectodermal tumor with a
      trabecular, adamantiform histology and prominent angiogenesis. Primitive
      neuroectodermal tumor was positive for vimentin, synaptophysin, neuron-specific
      enolase, CD99, and SOX2 and negative for both the FLI-1 fusion protein and the
      rearrangement of ESWR1 gene. The neoplasm exhibited a nonaggressive behavior
      similar to sarcoma botryoides of the adolescence, being alive and well 3 y after
      its presentation. This is possibly related to its polypoid nature and the absence
      of invasive features at its uterine insertion level. A conservative approach
      without further resection and chemotherapy was indicated taking into account the
      patient's age.

PMID- 22653356
TI  - Bartonella quintana-induced vulval bacillary angiomatosis.
AB  - Bacillary angiomatosis (BA) is an increasingly reported infection, mainly in
      patients with acquired immunodeficiency syndrome. Different epidemiological risk
      factors are associated with the transmission of the causative agents, Bartonella
      henselae and B. quintana. Vulval BA is described rarely. Two patients presented
      with a vulval mass (Patient 1) and a verrucous vulval growth (Patient 2), which
      were diagnosed clinically as tuberculosis and carcinoma, respectively. Patient 1
      also had pulmonary tuberculosis and Kaposi sarcoma. Biopsy of the vulval lesions
      confirmed BA, characterized by a multilobular proliferation of blood vessels that
      were lined by epithelioid endothelial cells. There were prominent intervascular
      neutrophils, karyorrhectic debris, and clumps of paravascular argyrophilic
      organisms. The biopsy from Patient 1 was deep dermal/subcutaneous in location and
      displayed foci of confluent suppuration. There was florid pseudoepitheliomatous
      hyperplasia in the biopsy from Patient 2. Molecular investigations confirmed
      intralesional B. quintana, hitherto unreported in vulval BA, as the causative
      agent in both biopsies. On follow-up, Patient 2 had developed additional lesions
      in the vulva and thigh, but all her lesions and the vulval mass (Patient 1)
      responded to erythromycin treatment. Patient 1 succumbed to tuberculosis.
      Heightened recognition of BA underpins rapid and optimal clinicopathological
      diagnosis, even in uncommon locations. Identification of the causative Bartonella
      species is important for appropriate, interventive social management.

PMID- 22653364
TI  - Hypoallergenic mutants of the Timothy grass pollen allergen Phl p 5 generated by
      proline mutations.
AB  - BACKGROUND: Phl p 5 is a major allergen of Timothy grass (Phleum pratense). A
      recombinant native Phl p 5 has already been used in clinical trials of allergen
      specific immunotherapy as a component of a cocktail of allergens. Recombinant
      hypoallergenic allergens should further improve the treatment by reducing the
      risk of anaphylactic reactions at an increased therapeutic dosage. Native Phl p 5
      is formed by alpha-helical regions separated by regions containing prolines. In
      order to generate hypoallergenic mutants, we studied the effect of proline
      mutations in single and multiple regions. METHODS: All mutants were analyzed by
      IgE inhibition assays and size exclusion chromatography with on-line mass
      determination. Selected mutants were additionally analyzed by field-flow
      fractionation, dynamic light scattering, circular dichroism spectroscopy,
      basophil activation and T-cell proliferation assays. RESULTS: Variants lacking
      prolines in a single region were obtained as soluble monomers. Six of eight
      molecules showed a slightly reduced IgE-binding capacity. Mutants carrying
      proline deletions in multiple regions formed monomers, dimers or insoluble
      aggregates. The mutant MPV.7 with five proline deletions and a substitution of
      proline 211 to leucine is monomeric, shows a strongly diminished IgE binding and
      maintains T-cell reactivity. The hydrodynamic radius and the content of the alpha
      helical structure of MPV.7 are well comparable with the wild-type allergen.
      CONCLUSIONS: The hypoallergenic Phl p 5 variant MPV.7 combines multiple proline
      deletions with a substitution of proline 211 to leucine and meets basic demands
      for a pharmaceutical application. MPV.7 is a promising candidate for grass pollen
      immunotherapy with a cocktail of recombinant hypoallergens.

PMID- 22653365
TI  - Cochlear implant insertion forces in microdissected human cochlea to evaluate a
      prototype array.
AB  - Cochlear implant array insertion forces are potentially related to cochlear
      trauma. We compared these forces between a standard (Digisonic SP; Neurelec,
      Vallauris, France) and an array prototype (Neurelec) with a smaller diameter. The
      arrays were inserted by a mechatronic tool in 23 dissected human cochlea
      specimens exposing the basilar membrane. The array progression under the basilar
      membrane was filmed together with dynamic force measurements. Insertion force
      profiles and depth of insertion were compared. The recordings showed lower
      insertion forces beyond 270 degrees  of insertion and deeper insertions with the
      thin prototype array. This will potentially allow larger cochlear coverage with
      less trauma.

PMID- 22653366
TI  - Bouveret's syndrome.

PMID- 22653367
TI  - Laxative prescriptions to cancer outpatients receiving opioids: a study from the
      Norwegian prescription database.
AB  - BACKGROUND: During opioid treatment of cancer pain, constipation is one of the
      most prevalent and bothersome side effects. Guidelines suggest that treatment
      with laxatives should be initiated when opioid therapy is started. AIM: This
      study aims: (1) to determine to what extent patients, starting on opioids due to
      cancer pain, receive laxatives; (2) to examine the temporal relationship between
      initiation of opioid therapy and initiation of treatment with laxatives; and (3)
      to study to which extent the treatment follows current guidelines. METHODS: Data
      from the Norwegian prescription database (NorPD) were used to investigate
      dispensed prescriptions of laxatives to outpatients in Norway, who are receiving
      opioids for cancer pain. Data from NorPD cover all dispensed prescriptions of
      drugs to outpatients, making it possible to follow patients over time. The study
      cohort was followed from 2005 to the end of 2008. RESULTS: Of 2,982 patients who
      started opioid therapy directly with WHO step III opioids, 1,325 patients (44.4
      %) did not receive laxatives during the study period. Only 738 patients (24.7 %)
      received laxatives at the same time as opioid therapy was initiated. Another 657
      patients (22.0 %) received laxatives after their initiation of opioids at some
      time during the study period. CONCLUSION: Of those who started directly on a
      strong opioid, only one fourth received laxatives concomitantly with the first
      opioid, and nearly half did not receive laxatives at all. These findings indicate
      that the current guidelines are not followed.

PMID- 22653368
TI  - A cross-sectional study of constipation and laxative use in advanced cancer
      patients: insights for revision of current practice.
AB  - PURPOSE: This study aimed to evaluate the bowel habit and laxative use in
      advanced cancer patients with constipation in palliative care unit. METHODS: It
      was a cross-sectional study using a self-designed questionnaire. RESULTS: A total
      of 225 patients were analysed. Among all patients, 92.0 % (207 patients) had any
      intervention for relief of constipation, including laxatives, suppositories,
      enemas, digital evacuation and Chinese herbal medicine, and 65.3 % (147 patients)
      were on laxatives prescribed by our doctors. The severity of constipation as
      assessed by the constipation visual analogue scale (CVAS) (0-7, 7 = most severe)
      was reported as no constipation (0-1) in 19.6 % of patients, constipation (2-4)
      in 50.7 % and severe constipation (5-7) in 29.8 %. More patients with severe
      constipation, as compared with patients with constipation and no constipation,
      reported inadequate pushing force (83.6 vs. 47.4 vs. 6.8 %), sense of incomplete
      defecation (40.3 vs. 14.9 vs. 6.8 %) and difficult defecation (58.2 vs. 26.3 vs.
      0 %), all p < 0.001, but there was no difference in stool types as assessed by
      Bristol Stool Scale (p = 0.303). Patients not on opioids, as compared with
      patients on strong opioids, had similar CVAS scores and description of
      constipation but had least laxatives prescribed (60.2 vs. 78.9 %, p = 0.012).
      CONCLUSION: Evaluation of constipation should not rely on stool form or
      consistency alone, and patient's description of constipation is worth
      consideration. Constipation is also a problem in patients not on opioids and more
      attention is required. A revisit to existing guidelines is needed.

PMID- 22653369
TI  - Temperature- and time-dependent changes in TLR2-activated microglial NF-kappaB
      activity and concentrations of inflammatory and anti-inflammatory factors.
AB  - PURPOSE: Therapeutic hypothermia protects neurons following injury to the central
      nervous system (CNS). Microglia express toll-like receptors (TLRs) that play
      significant roles in pathological processes in sterile CNS injury. We have
      examined the effects of culture temperature on the TLR2-activated microglial
      production of cytokines and nitric oxide (NO), which are known to be associated
      with CNS damage, and the possible involvement of nuclear factor-kappaB (NF
      kappaB) activation underlying such effects. METHODS: Rat microglia were cultured
      with a selective TLR2 agonist, Pam(3)CSK(4), under hypothermic, normothermic, and
      hyperthermic conditions, and with Pam(3)CSK(4) in the presence of a NF-kappaB
      activation inhibitor at 37  degrees C. Cytokine and NO levels and NF-kappaB p65
      activation were measured. RESULTS: The production of tumor necrosis factor-alpha
      (TNF-alpha), interleukin-10 (IL-10), and NO and the activation of NF-kappaB p65
      were reduced by hypothermia, but augmented by hyperthermia at 3-6, 24-48, 48, and
      0.5 h, post-treatment initiation, respectively. Pharmacological inhibition of NF
      kappaB activation impaired the Pam(3)CSK(4)-induced TNF-alpha, IL-10, and NO
      production. CONCLUSIONS: In TLR2-activated microglia, hypothermia reduced, while
      hyperthermia increased, the early activation of NF-kappaB and the subsequent NF
      kappaB-mediated production of TNF-alpha, IL-10, and NO in a time-dependent
      manner, suggesting that attenuation of these factors via suppression of NF-kappaB
      in microglia is one possible neuroprotective mechanism of therapeutic
      hypothermia. Moreover, temperature-dependent changes in microglial TNF-alpha
      production during the early phase and IL-10 and NO production during the late
      phase indicate that these factors might be useful as clinical markers to monitor
      hypothermia-related neuronal protection and hyperthermia-related neuronal injury.

PMID- 22653370
TI  - Inhalation of NO during myocardial ischemia reduces infarct size and improves
      cardiac function.
AB  - PURPOSE: Bioactive NO carriers in circulating blood formed during NO inhalation
      selectively distribute blood flow to areas in need, and may thus improve
      collateral perfusion to the area-at-risk in acute myocardial infarction (AMI).
      Here, we tested the hypothesis that NO inhalation during the ischemic phase of
      AMI may improve left ventricular function and reduce infarct size in rats.
      METHODS: Following left anterior descending coronary artery (LAD) occlusion, rats
      received 50 ppm NO for 2 h of ischemia, during subsequent 3 h of reperfusion, or
      for 5 h of ischemia and reperfusion. Effects of inhaled NO were compared to those
      of intravenous nitrite as a putative carrier formed during NO inhalation.
      Downstream signaling via soluble guanylate cyclase was tested by inhibition with
      1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). RESULTS: NO inhalation during
      myocardial ischemia increased left ventricular systolic pressure, contractility,
      relaxation, and cardiac output, and reduced myocardial infarction size and area
      at-risk as compared to untreated controls. NO inhalation during the reperfusion
      phase caused a comparable protective effect. Combined inhalation during ischemia
      and reperfusion did not further improve left ventricular hemodynamics, but had an
      additive protective effect on the myocardial area-at-risk. NO inhalation
      increased circulating nitrite levels, and mimicking of this effect by intravenous
      nitrite infusion achieved similar protection as NO inhalation during myocardial
      ischemia, while ODQ blocked the protective NO effect. CONCLUSIONS: Inhalation of
      NO during myocardial ischemia improves left ventricular function and reduces
      infarct size by mechanisms that increase levels of circulating nitrite and
      involve soluble guanylate cyclase. NO inhalation may represent a promising early
      intervention in AMI.

PMID- 22653371
TI  - Point of care ultrasound for sepsis management in resource-limited settings: time
      for a new paradigm for global health care.

PMID- 22653373
TI  - Perioperative amplitude-integrated EEG and neurodevelopment in infants with
      congenital heart disease.
AB  - PURPOSE: Perioperative brain injury is common in young infants undergoing cardiac
      surgery. We aimed to determine the relationship between perioperative electrical
      seizures, the background pattern of amplitude-integrated electroencephalography
      (aEEG) and 2-year neurodevelopmental outcome in young infants undergoing surgery
      for congenital heart disease. METHODS: A total of 150 newborn infants undergoing
      cardiac surgery underwent aEEG monitoring prior to and during surgery, and for 72
      h postoperatively. Two blinded assessors reviewed the aEEGs for seizure activity
      and background pattern. Survivors underwent neurodevelopmental outcome assessment
      using the Bayley Scales of Infant Development (3rd edn.) at 2 years. RESULTS: The
      median age at surgery was 7 days (IQR 4-11). Cardiopulmonary bypass was used in
      83 %. Perioperative electrical seizures occurred in 30 %, of whom 1/4 had a
      clinical correlate, but were not associated with 2-year outcome. Recovery to a
      continuous background occurred at a median 6 (3-13) h and sleep-wake cycling
      recovered at 21 (14-30) h. Prolonged aEEG recovery was associated with increased
      mortality and worse neurodevelopmental outcome. Failure of the aEEG to recover to
      a continuous background by 48 postoperative hours was associated with impairment
      in all outcome domains (p < 0.05). Continued abnormal aEEG at 7 postoperative
      days was highly associated with mortality (p < 0.001). CONCLUSIONS: Perioperative
      seizures were common in this cohort of infants but did not impact on 2-year
      neurodevelopmental outcome. Delayed recovery in aEEG background was associated
      with increased risk of early mortality and worse neurodevelopment. Ongoing
      monitoring of the survivors is essential to determine the longer-term
      significance of these findings.

PMID- 22653374
TI  - Clinical effects of a nine-month web-based intervention in subacute non-specific
      low back pain patients: a randomized controlled trial.
AB  - OBJECTIVE: To test the clinical effect of a web-based lower back pain
      intervention on quality of life and selected lower back pain outcomes. DESIGN: A
      prospective single-blinded randomized intervention. SETTING: Occupational
      preventive service. SUBJECTS: One hundred office workers with non-specific
      subacute lower back pain. INTERVENTION: The 50 intervention group subjects were
      educated daily about sitting correctly and asked to perform exercises shown by
      video demonstrations on the university website. The exercise routines included
      strengthening, mobility and stretching exercises focused on the postural
      stability muscles. The 50 control group subjects only received standard
      occupational care. MEASURES: Outcomes were measured by the EuroQol questionnaire
      five dimensions three levels, the Oswestry Disability Index, and the StarT Back
      Screening Tool questionnaires. At nine months, the intervention group outcomes
      were compared to the baseline data and the control group outcomes. RESULTS: For
      97% (n = 45) of the experimental group quality of life (clinical utility)
      improved significantly; 3.58 times greater than the control group. Oswestry
      Disability Index showed an odds ratio (OR) of 5.42 with a 37% (n = 17) change for
      the intervention group with respect to the control group. With regard to the
      StarT Back Screening Tool, 76% (n = 35) of the intervention group improved their
      clinical state (odds ratio = 3.04 with respect to the control group improvement).
      Logistic regression analysis revealed positive changes in EuroQol questionnaire,
      increasing the likelihood of observing positive changes in StarT Back Screening
      Tool (OR = 15.5) and Oswestry Disability Index (OR = 4.5). CONCLUSIONS: The
      intervention showed clinical improvements in quality of life and selected lower
      back pain outcomes in the experimental group compared to the control group.

PMID- 22653375
TI  - Patient-focused goal planning process and outcome after spinal cord injury
      rehabilitation: quantitative and qualitative audit.
AB  - OBJECTIVE: To evaluate the process and outcome of a multidisciplinary inpatient
      goal planning rehabilitation programme on physical, social and psychological
      functioning for patients with spinal cord injury. DESIGN: Clinical audit:
      quantitative and qualitative analyses. SETTING: Specialist spinal injury unit,
      Perth, Australia. SUBJECTS: Consecutive series of 100 newly injured spinal cord
      injury inpatients. MAIN MEASURE(S): The Needs Assessment Checklist (NAC), patient
      focused goal planning questionnaire and goal planning progress form. RESULTS: The
      clinical audit of 100 spinal cord injured patients revealed that 547 goal
      planning meetings were held with 8531 goals stipulated in total. Seventy-five per
      cent of the goals set at the first goal planning meeting were achieved by the
      second meeting and the rate of goal achievements at subsequent goal planning
      meetings dropped to 56%. Based on quantitative analysis of physical, social and
      psychological functioning, the 100 spinal cord injury patients improved
      significantly from baseline to discharge. Furthermore, qualitative analysis
      revealed benefits consistently reported by spinal cord injury patients of the
      goal planning rehabilitation programme in improvements to their physical, social
      and psychological adjustment to injury. CONCLUSIONS: The findings of this
      clinical audit underpin the need for patient-focused goal planning rehabilitation
      programmes which are tailored to the individual's needs and involve a
      comprehensive multidisciplinary team.

PMID- 22653376
TI  - Embedded proteins and sacrificial bonds provide the strong adhesive properties of
      gastroliths.
AB  - The adhesive properties of gastroliths from a freshwater crayfish (Cherax
      quadricarinatus) were quantified by colloidal probe atomic force microscopy (AFM)
      between heavily demineralized gastrolith microparticles and gastrolith substrates
      of different composition. Combined AFM and transmission electron microscopy
      studies demonstrated that the sequential detachment and large adhesion energies
      that characterise the adhesive behaviour of a native gastrolith substrate are
      dominated by sacrificial bonds between chitin fibres and between chitin fibres
      and CaCO(3). The sacrificial bonds were shown to be strongly related to the
      gastrolith proteins and when the majority of these proteins were removed by
      ethylenediaminetetraacetic acid (EDTA), the sequential detachment disappeared and
      the adhesive energy was reduced by more than two orders of magnitude.

PMID- 22653377
TI  - The unusual cell biology of the hyperthermophilic Crenarchaeon Ignicoccus
      hospitalis.
AB  - The Crenarchaeon Ignicoccus hospitalis is an anaerobic, obligate
      chemolithoautotrophic hyperthermophile, growing by reduction of elemental sulfur
      using molecular hydrogen as electron donor. Together with Nanoarchaeum equitans
      it forms a unique, archaeal biocoenosis, in which I. hospitalis serves as host
      for N. equitans. Both organisms can be cultivated in a stable coculture which is
      mandatory for N. equitans but not for I. hospitalis. This strong dependence is
      affirmed by the fact that N. equitans obtains its lipids and amino acids from the
      host. I. hospitalis cells exhibit several unique features: they can adhere to
      surfaces by extracellular appendages ('fibers') which are not used for motility;
      they use a novel CO(2) fixation pathway, the dicarboxylate/4-hydroxybutyrate
      pathway; and they exhibit a unique cell envelope for Archaea consisting of two
      membranes but lacking an S-layer. These membranes form two cell compartments, a
      tightly packed cytoplasm surrounded by a weakly staining intermembrane
      compartment (IMC) with a variable width from 20 to 1,000 nm. In this IMC, many
      round or elongated vesicles are found which may function as carriers of lipids or
      proteins out of the cytoplasm. Based on immuno-EM analyses and immuno
      fluorescence experiments it was demonstrated recently that the A(1)A(O) ATP
      synthase, the H(2):sulfur oxidoreductase complex and the acetyl-CoA synthetase
      (ACS) of I. hospitalis are located in its outermost membrane. Therefore, this
      membrane is energized and is here renamed as "outer cellular membrane" (OCM).
      Among all prokaryotes possessing two membranes in their cell envelope, I.
      hospitalis is the first organism with an energized outermost membrane and ATP
      synthesis outside the cytoplasm. Since DNA and ribosomes are localized in the
      cytoplasm, energy conservation is separated from information processing and
      protein biosynthesis in I. hospitalis. This raises questions concerning the
      function and characterization of the two membranes, the two cell compartments and
      of a possible ATP transfer to N. equitans.

PMID- 22653379
TI  - After-hours care and its coordination with primary care in the U.S.
AB  - BACKGROUND: Despite expectations that medical homes provide "24 * 7 coverage"
      there is little to guide primary care practices in developing sustainable models
      for accessible and coordinated after-hours care. OBJECTIVE: To identify and
      describe models of after-hours care in the U.S. that are delivered in primary
      care sites or coordinated with a patient's usual primary care provider. DESIGN:
      Qualitative analysis of data from in-depth telephone interviews. SETTING: Primary
      care practices in 16 states and the organizations they partner with to provide
      after-hours coverage. PARTICIPANTS: Forty-four primary care physicians, practice
      managers, nurses and health plan representatives from 28 organizations. APPROACH:
      Analyses examined after-hours care models, facilitators, barriers and lessons
      learned. RESULTS: Based on 28 organizations interviewed, five broad models of
      after-hours care were identified, ranging in the extent to which they provide
      continuity and patient access. Key themes included: 1) The feasibility of a model
      varies for many reasons, including patient preferences and needs, the local
      health care market supply, and financial compensation; 2) A shared electronic
      health record and systematic notification procedures were extremely helpful in
      maintaining information continuity between providers; and 3) after-hours care is
      best implemented as part of a larger practice approach to access and continuity.
      CONCLUSION: After-hours care coordinated with a patient's usual primary care
      provider is facilitated by consideration of patient demand, provider capacity, a
      shared electronic health record, systematic notification procedures and a broader
      practice approach to improving primary care access and continuity. Payer support
      is important to increasing patients' access to after-hours care.

PMID- 22653380
TI  - Variation in primary care physicians' colorectal cancer screening recommendations
      by patient age and comorbidity.
AB  - BACKGROUND: Screening patterns among primary care physicians (PCPs) may be
      influenced by patient age and comorbidity. Colorectal cancer (CRC) screening has
      little benefit among patients with limited life expectancy. OBJECTIVE: To
      characterize the extent to which PCPs modify their recommendations for CRC
      screening based upon patients' increasing age and/or worsening comorbidity
      DESIGN: Cross-sectional, nationally representative survey. PARTICIPANTS: The
      study comprised primary care physicians (n = 1,266) including general internal
      medicine, family practice, and obstetrics-gynecology physicians. MAIN MEASURES:
      Physician CRC screening recommendations among patients of varying age and
      comorbidity were measured based upon clinical vignettes. Independent variables in
      adjusted models included physician and practice characteristics. KEY RESULTS: For
      an 80-year-old patient with unresectable non-small cell lung cancer (NSCLC), 25 %
      of PCPs recommended CRC screening. For an 80-year-old patient with ischemic
      cardiomyopathy (New York Heart Association, Class II), 71 % of PCPs recommended
      CRC screening. PCPs were more likely to recommend fecal occult blood testing than
      colonoscopy as the preferred screening modality for a healthy 80-year-old,
      compared to healthy 50- or 65-year-old patients (19 % vs. 5 % vs. 2 % p < 0.001).
      For an 80-year-old with unresectable NSCLC, PCPs who were an obstetrics
      gynecology physician were more likely to recommend CRC screening, while those
      with a full electronic medical record were less likely to recommend screening.
      CONCLUSIONS: PCPs consider comorbidity when screening older patients for CRC and
      may change the screening modality from colonoscopy to FOBT. However, a sizable
      proportion of PCPs would recommend screening for patients with advanced cancer
      who would not benefit. Understanding the mechanisms underlying these patterns
      will facilitate the design of future medical education and policy interventions
      to reduce unnecessary care.

PMID- 22653381
TI  - A study of racial/ethnic differences in treatment preferences among lupus
      patients.
AB  - OBJECTIVES: To determine whether there are racial/ethnic differences in the
      willingness of SLE patients to receive CYC or participate in clinical trials, and
      whether demographic, psychosocial and clinical characteristics contribute to
      these differences. METHODS: Data from 120 African-American and 62 white lupus
      patients were evaluated. Structured telephone interviews were conducted to
      determine treatment preferences, as well as to study characteristics and beliefs
      that may affect these preferences. Data were analysed using serial hierarchical
      multivariate logistic regression and deviances were calculated from a saturated
      model. RESULTS: Compared with their white counterparts, African-American SLE
      patients expressed less willingness to receive CYC (67.0% vs 84.9%, P = 0.02) if
      their lupus worsened. This racial/ethnic difference remained significant after
      adjusting for socioeconomic and psychosocial variables. Logistic regression
      analysis showed that African-American race [odds ratio (OR) 0.29, 95% CI 0.10,
      0.80], physician trust (OR 1.05, 95% CI 1.00, 1.12) and perception of treatment
      effectiveness (OR 1.40, 95% CI 1.22, 1.61) were the most significant determinants
      of willingness to receive CYC. A trend in difference by race/ethnicity was also
      observed in willingness to participate in a clinical trial, but this difference
      was not significant. CONCLUSION: This study demonstrated reduced likelihood of
      accepting CYC in African-American lupus patients compared with white lupus
      patients. This racial/ethnic variation was associated with belief in medication
      effectiveness and trust in the medical provider, suggesting that education about
      therapy and improved trust can influence decision-making among SLE patients.

PMID- 22653382
TI  - Continuous efficacy of etanercept in severe and advanced ankylosing spondylitis:
      results from a 12-week open-label extension of the SPINE study.
AB  - OBJECTIVE: To evaluate the longer-term efficacy of etanercept in patients with
      severe and advanced active AS. METHODS: Seventy-seven patients who completed the
      randomized, double-blind, placebo-controlled 12-week SPINE study enrolled in a 12
      week open-label extension and received s.c. etanercept 50 mg once weekly. The
      etanercept/etanercept group received a total of 24 weeks treatment with
      etanercept (n = 38); the placebo/etanercept group received placebo during the
      double-blind study then 12 weeks' etanercept treatment during the open-label
      extension (n = 39). RESULTS: At the end of the open-label extension, BASDAI
      scores in the etanercept/etanercept group had further decreased beyond reductions
      observed during the double-blind study [mean (s.d.) change from baseline -37.6
      (22.4) at end of extension vs -27.4 (23.8) at end of double-blind study]. Mean
      (s.d.) BASDAI scores also improved in the placebo/etanercept group once switched
      to etanercept [-28.6 (24.3) vs -15.0 (20.0)]. Similar trends were observed in
      BASFI and BASMI scores. In the placebo/etanercept group, total back pain
      decreased to similar levels achieved in the etanercept group in the double-blind
      study. Pain levels continued to decrease with longer-term etanercept therapy in
      the etanercept/etanercept group. CONCLUSION: Despite the improvements in symptoms
      and inflammatory markers observed shortly after initiation of once-weekly
      etanercept, there was no notable plateauing effect on patient-reported outcomes.
      Indeed, signs and symptoms of severe and advanced active AS continued to improve
      after up to 24 weeks, treatment with etanercept.

PMID- 22653383
TI  - Validation of the Illness Perception Questionnaire for Schizophrenia in a German
      speaking sample of outpatients with chronic schizophrenia.
AB  - BACKGROUND: Because the mere definition of insight from the therapist's viewpoint
      may not be sufficient to identify treatment targets for adherence enhancement, we
      need assessment strategies which are more sensitive to the patient's perspective.
      Illness perception (IP), defined as the beliefs a patient holds about his/her
      health problems, has been shown to affect coping in the context of a physical or
      mental illness, e.g. compliance behaviour. To assess IP in people diagnosed with
      schizophrenia, the Illness Perception Questionnaire for Schizophrenia (IPQS) was
      developed. The aim of the present study was to analyse the psychometric
      properties of the German version of the IPQS. SAMPLING AND METHODS: The study
      sample consisted of 128 German-speaking outpatients suffering from chronic
      schizophrenia or schizoaffective disorder. To achieve comparability with the
      validation of the English scale version, the same constructs were assessed:
      psychopathology, depression, and beliefs about medication. Furthermore, insight
      into one's illness was assessed. Internal consistency, test-retest reliability
      and construct validity including convergent and discriminant validity were
      analysed. RESULTS: Five of eight IPQS subscales were found to be internally
      reliable and all subscales demonstrated high stability over time. Correlations
      with validity measures indicated that the subscales assess dimensions of a
      construct, which is distinct from psychopathology, depression, beliefs about
      medication and insight, except for the Identity subscale which substantially
      overlapped with measures of insight. CONCLUSIONS: The German version of the IPQS
      is an essentially reliable and valid measure of IP for German-speaking people
      with a schizophrenia spectrum disorder. This may encourage its usage in further
      studies investigating the impact of subjective beliefs about mental health
      problems on outcome and recovery in schizophrenia.

PMID- 22653384
TI  - Potential antitumor therapeutic strategies of human amniotic membrane and
      amniotic fluid-derived stem cells.
AB  - As stem cells are capable of self-renewal and can generate differentiated
      progenies for organ development, they are considered as potential source for
      regenerative medicine and tissue replacement after injury or disease. Along with
      this capacity, stem cells have the therapeutic potential for treating human
      diseases including cancers. According to the origins, stem cells are broadly
      classified into two types: embryonic stem cells (ESCs) and adult stem cells. In
      terms of differentiation potential, ESCs are pluripotent and adult stem cells are
      multipotent. Amnion, which is a membranous sac that contains the fetus and
      amniotic fluid and functions in protecting the developing embryo during
      gestation, is another stem cell source. Amnion-derived stem cells are classified
      as human amniotic membrane-derived epithelial stem cells, human amniotic membrane
      derived mesenchymal stem cells and human amniotic fluid-derived stem cells. They
      are in an intermediate stage between pluripotent ESCs and lineage-restricted
      adult stem cells, non-tumorigenic, and contribute to low immunogenicity and anti
      inflammation. Furthermore, they are easily available and do not cause any
      controversial issues in their recovery and applications. Not only are amnion
      derived stem cells applicable in regenerative medicine, they have anticancer
      capacity. In non-engineered stem cells transplantation strategies, amnion-derived
      stem cells effectively target the tumor and suppressed the tumor growth by
      expressing cytotoxic cytokines. Additionally, they also have a potential as novel
      delivery vehicles transferring therapeutic genes to the cancer formation sites in
      gene-directed enzyme/prodrug combination therapy. Owing to their own advantageous
      properties, amnion-derived stem cells are emerging as a new candidate in
      anticancer therapy.

PMID- 22653386
TI  - Prevention of tumor growth by needle-free jet injection of anti-C7orf24 siRNA.
AB  - Chromosome 7 open reading frame 24 (C7orf24), which was identified by proteome
      analysis, is upregulated in various types of cancer and is associated with
      cellular proliferation. However, in vivo antitumor effect by knockdown of C7orf24
      has not been clarified. In this study, we investigated that the antitumor effect
      of anti-C7orf24 small interfering RNA (siRNA) administered by needle-free jet
      injection (JI) on lung cancer-bearing mice. Transfection of anti-C7orf24 siRNA
      induced cytotoxicity in cultured human lung cancer cells through specific
      knockdown of C7orf24. Furthermore, JI could effectively deliver anti-C7orf24
      siRNA to tumor tissues, and as a result tumor growth was significantly inhibited.
      Immunohistochemical analysis revealed that C7orf24 levels were significantly
      reduced within tumor tissues collected from anti-C7orf24 siRNA-administered mice,
      indicating that the knockdown of C7orf24 induced cytotoxicity in tumor tissue. In
      conclusion, these data show for the first time that knockdown of C7orf24 prevents
      tumor growth in vivo following JI-mediated the siRNA delivery.

PMID- 22653388
TI  - Successful treatment of pudendal neuralgia with tricolumn spinal cord
      stimulation:  case report.
AB  - BACKGROUND AND IMPORTANCE: There is large variation in the success of
      decompressive surgery for pudendal neuralgia (PN), the most chronic, disabling
      form of perineal pain. We attempt to determine whether spinal cord stimulation
      using new-generation multicolumn leads could form part of the treatment algorithm
      for refractory PN. CLINICAL PRESENTATION: A man with PN that was unresponsive to
      conventional treatment demonstrated a neuropathic component and had a negative
      response to nerve infiltrations (so he was not indicated for decompressive
      surgery) and a positive response to perianal transcutaneous electrical nerve
      stimulation and was implanted with a 16-contact surgical lead at the level of
      conus medullaris, allowing multicolumn stimulation. Using transverse
      combinations, it was possible to obtain 100% paresthesia over the perineal area
      without unwanted dorsal root stimulation. Perineal and radicular pain was
      successfully relieved for up to 12 months (80% and 60% reduction in the visual
      analogue scale scores, respectively), with an improvement in all quality of life
      domains and a reduction in drug consumption. CONCLUSION: Spinal cord stimulation
      using a 16-contact lead may be a viable therapeutic option for patients with
      refractory PN for whom decompressive surgery is contraindicated.

PMID- 22653385
TI  - Systemic delivery of a breast cancer-detecting adenovirus using targeted
      microbubbles.
AB  - One of the major limitations of cancer gene therapy using recombinant human
      adenovirus (Ad) is rapid Ad inactivation from systemic delivery. To eliminate
      this, biotin-coated ultrasound contrast agents, or microbubbles (MBs), were
      streptavidin-coupled with biotinylated antibodies to three distinct tumor
      vasculature-associated receptors (alpha(V)beta(3) integrin, P-selectin and
      vascular endothelial growth factor receptor-2) for systemic targeting of a
      previously generated vector Ad5/3-Id1-SEAP-Id1-mCherry. This cancer-specific,
      dual-reporter vector was loaded in the targeted MBs and confirmed by confocal
      microscopy. MB loading capacity was estimated by functional assays as 4.72 +/-
      0.2 plaque forming unit (PFU) per MB. Non-loaded (free) Ad particles were
      effectively inactivated by treatment with human complement. The Ad-loaded,
      targeted-MBs were injected systemically in mice bearing MDA-MB-231 tumors (Grp 1)
      and compared with two control groups: Ad-loaded, non-targeted MBs (Grp 2) and
      free Ad (Grp 3) administered under the same conditions. Two days after
      administration the blood levels of secreted embryonic alkaline phosphatase (SEAP)
      reporter in Grp 1 mice (16.1 ng ml(-1) +/- 2.5) were significantly higher
      (P<0.05) than those in Grp 2 (9.75 ng ml(-1) +/- 1.5) or Grp 3 (4.26 ng ml(-1) +/
      2.5) animals. The targeted Ad delivery was also confirmed by fluorescence
      imaging. Thus, Ad delivery by targeted MBs holds potential as a safe and
      effective system for systemic Ad delivery for the purpose of cancer screening.

PMID- 22653389
TI  - Single center experience with pipeline stent:  feasibility, technique, and
      complications.
AB  - BACKGROUND: Endovascular coil embolization is an established method of treatment
      for intracranial aneurysms. The pipeline embolization device (PED) is a low
      porosity endovascular stent designed to reconstruct the parent artery and
      decrease blood flow into the aneurysm. OBJECTIVE: To report a series of 36
      patients treated with the PED. METHODS: Thirty-six patients underwent PED
      placement for aneurysm at the Jefferson Hospital for Neuroscience from October
      2010 to November 2011. Clinical charts were reviewed. RESULTS: Thirty-six
      patients with 42 aneurysms were treated (3 male; 33 female; ages, 34-82; mean
      age, 60.1 years). Forty-one aneurysms were located in the anterior circulation,
      whereas one was located at the vertebrobasilar junction. PED placement was
      successful in all patients and resulted in stasis within all treated aneurysms.
      Symptomatic postoperative complications were witnessed in 13.9% (n = 5) of
      patients. These complications included intracerebral hemorrhage (n = 4),
      dissection (n = 1), symptomatic stroke (n = 2), and death (n = 1). CONCLUSION:
      Treatment of simple or complex intracranial aneurysms with PEDs alone or in
      conjunction with coil embolization is technically feasible, and the deployment
      technique requires a high degree of endovascular skills. Major perioperative
      adverse events must be studied. Respect for the indications of the procedure is
      crucial to justify the risk.

PMID- 22653387
TI  - Expression of FMS-like tyrosine kinase 3 ligand by oncolytic herpes simplex virus
      type I prolongs survival in mice bearing established syngeneic intracranial
      malignant glioma.
AB  - BACKGROUND: Glioblastoma is a fatal brain tumor in needing urgent effective
      therapy. Treatments with both oncolytic viruses and immunotherapy have shown
      preclinical efficacy and clinical promise. We sought to exploit possible
      synergies between oncolytic herpes simplex virus type 1 (oHSV-1) infection of
      intracranial gliomas and delivery of immune-stimulating fms-like tyrosine kinase
      3 ligand (Flt3L) by engineering a herpes vector to express the cytokine.
      OBJECTIVE: To construct an oHSV-1 vector that expresses high levels of Flt3L and
      examine its antiglioma efficacy in an immunocompetent murine model. METHODS:
      G47Delta and a bacterial artificial chromosome system were used to generate a
      novel oHSV-1, termed G47Delta-Flt3L, expressing Flt3L. Cytokine expression was
      confirmed, and G47Delta-Flt3L was injected intratumorally into established
      intracranial CT-2A gliomas in syngeneic C57/Bl6 mice. Animals were followed for
      survival and assessed by the Kaplan-Meier method. RESULTS: G47Delta-Flt3L
      expressed high levels of Flt3L in culture. Expression of Flt3L affected neither
      viral replication nor had a cytotoxic effect on CT2A glioma cells. Direct
      inoculation into intracerebral CT2A glioma cells resulted in high levels of
      detectable Flt3L in mouse blood and was superior to parental G47Delta in
      prolonging survival in glioma-bearing animals. CONCLUSION: Treatment with
      G47Delta-Flt3L improves survival of glioma-bearing mice.

PMID- 22653390
TI  - The relationship between cerebral blood flow autoregulation and cerebrovascular
      pressure reactivity after traumatic brain injury.
AB  - BACKGROUND: Cerebrovascular pressure reactivity is the principal mechanism of
      cerebral autoregulation. Assessment of cerebral autoregulation can be performed
      by using the mean flow index (Mx) based on transcranial Doppler ultrasonography.
      Cerebrovascular pressure reactivity can be monitored by using the pressure
      reactivity index (PRx), which is based on intracranial pressure monitoring. From
      a practical point of view, PRx can be monitored continuously, whereas Mx can only
      be monitored in short periods when transcranial Doppler probes can be applied.
      OBJECTIVE: To assess to what degree impairment in pressure reactivity (PRx) is
      associated with impairment in cerebral autoregulation (Mx). METHODS: A database
      of 345 patients with traumatic brain injury was screened for data availability
      including simultaneous Mx and PRx monitoring. Absolute differences, temporal
      changes, and association with outcome of the 2 indices were analyzed. RESULTS: A
      total of 486 recording sessions obtained from 201 patients were available for
      analysis. Overall a moderate correlation between Mx and PRx was found (r = 0.58;
      P < .001). The area under the receiver operator characteristic curve designed to
      detect the ability of PRx to predict impaired cerebral autoregulation was 0.700
      (95% confidence interval: 0.607-0.880). Discrepancies between Mx and PRx were
      most pronounced at an intracranial pressure of 30 mm Hg and they were
      significantly larger for patients who died (P = .026). Both Mx and PRx were
      significantly lower at day 1 postadmission in patients who survived than in those
      who died (P < .01). CONCLUSION: There is moderate agreement between Mx and PRx.
      Discrepancies between Mx and PRx are particularly significant in patients with
      sustained intracranial hypertension. However, for clinical purposes, there is
      only limited interchangeability between indices.

PMID- 22653391
TI  - Submandibular high-flow bypass in the treatment of skull base lesions: an
      analysis of long-term outcome.
AB  - BACKGROUND: Cerebral bypass surgery remains an integral part of the treatment of
      complex skull base tumors and unclippable aneurysms. OBJECTIVE: The authors
      retrospectively analyzed a single-surgeon experience using a high-flow
      submandibular-infratemporal saphenous vein graft bypass technique after carotid
      artery sacrifice in the resection of complex skull base tumors and carotid
      isolation in unclippable aneurysms. METHODS: Data on indications, surgical
      technique, bypass patency, complications, and outcome were collected for patients
      treated with adjunctive submandibular high-flow bypass for skull base lesions.
      RESULTS: Eleven patients (age range, 13-77 years) were treated for various skull
      base lesions: 4 patients were treated for skull base tumors with resection of the
      internal carotid artery (ICA), 6 were treated for aneurysms not amenable to
      clipping, and one was treated for invasive Mucor infection. With the use of a
      saphenous vein graft, a high-flow bypass was created from the high cervical ICA
      or external carotid artery to ICA or middle cerebral artery by means of a
      submandibular-infratemporal route. Postoperative angiography indicated bypass
      patency in 10 of 11 patients. There was no operative mortality. Follow-up of up
      to 12 years (mean, 56 months) was achieved. CONCLUSION: Direct high-flow
      submandibular-infratemporal interpositional saphenous vein bypass graft is an
      effective and durable technique for the treatment of complex skull base lesions
      where ICA revascularization is indicated.

PMID- 22653392
TI  - Assessment of a quick reference table algorithm for determining initial
      postoperative pressure settings of programmable pressure valves in patients with
      idiopathic normal pressure hydrocephalus: SINPHONI subanalysis.
AB  - BACKGROUND: Management of overdrainage complications in shunted patients with
      idiopathic normal pressure hydrocephalus (INPH) remains a difficult task despite
      the use of programmable pressure valves. OBJECTIVE: To assess the usefulness of a
      quick reference table (QRT) algorithm for achieving a suitable initial
      programmable pressure valve setting in INPH patients who participated in the
      Study for INPH on Neurological Improvement (SINPHONI). METHODS: One hundred
      registered patients diagnosed with probable INPH were treated with
      ventriculoperitoneal shunts using Codman-Hakim programmable valves (CHPVs). In
      this series, the initial CHPV setting was decided prospectively according to the
      QRT algorithm. Shunt effectiveness, complications, and the number of CHPV
      readjustments during follow-up periods were investigated. RESULTS: Eighty
      patients were considered better than shunt responders (more than 1 point
      improvement in modified Rankin scale at any follow-up period). Readjustments of
      CHPVs within 3 months after treatment with ventriculoperitoneal shunt were
      performed 56 times in 44 cases (44%, 0.56 times/patient). Low-pressure headache
      occurred in 9 patients, all of whom improved by readjustment alone. Nontraumatic
      subdural fluid collections and chronic subdural hematomas occurred in 15 cases
      (15%); however, most of the cases were subclinical and improved after CHPV
      readjustments alone. Burr hole irrigation was necessary in only 1 case.
      CONCLUSION: Use of the QRT algorithm was associated with a decrease in
      postoperative CHPV readjustments and serious overdrainage complications during
      the follow-up period. The QRT algorithm is an easy, safe, and effective method
      for determining the initial CHPV pressure setting in INPH patients.

PMID- 22653393
TI  - Myoepithelioma of the skull:  a case report.
AB  - BACKGROUND AND IMPORTANCE: Myoepithelioma of bone is a rare osseous tumor thought
      to be related to myoepithelial lesions found at other anatomic sites such as the
      salivary gland and skin. These tumors are composed of varying proportions of
      epithelial and myoepithelial cells and exhibit a spectrum of biologic behavior
      ranging from benign to malignant. We present the first reported case of
      myoepithelioma of the skull. CLINICAL PRESENTATION: A 20-year-old white woman
      presented with a persistent right parieto-occipital skull nodule, relating its
      presence to a fall on the site 2 years previously. The nodule had become painful
      in the past 2 months. Her past medical history and workup were otherwise
      unremarkable. The initial biopsy was inconclusive for diagnosis. The lytic bone
      lesion was subsequently resected, and histopathological examination showed a
      proliferation of epithelioid cells in a myxochondroid background. Fluorescence in
      situ hybridization studies revealed a rearrangement of the EWSR1 locus. The
      morphologic and molecular findings were consistent with the diagnosis of
      myoepithelioma of bone. CONCLUSION: Six months after surgery, the patient is
      doing well with no evidence of recurrence. This case illustrates the clinical
      presentation, histopathology, and molecular findings of a myoepithelioma of the
      skull with successful surgical treatment. Because myoepitheliomas with benign
      morphological appearance may rarely act aggressively, long-term clinical follow
      up is warranted.

PMID- 22653394
TI  - Ruptured de novo aneurysm arising at a site remote from the anastomosis 14 years
      after superficial temporal artery-middle cerebral artery bypass:  a case report.
AB  - BACKGROUND AND IMPORTANCE: The long-term outcome of superficial temporal artery
      (STA)-middle cerebral artery (MCA) bypass is unclear. We report a very rare case
      of a de novo aneurysm after bypass surgery. CLINICAL PRESENTATION: A 57-year-old
      woman who underwent STA-MCA bypass and internal carotid artery aneurysm treatment
      14 years earlier developed a subarachnoid hemorrhage and a temporal lobe hematoma
      on the same side as the anastomosis. Angiography showed excellent patency of the
      STA bypass and a ruptured de novo saccular aneurysm at a site remote from the
      anastomosis. Neck clipping and hematoma evacuation were performed on the second
      day, and postoperative angiography showed complete aneurysmal clipping. The
      aneurysm was considered to be caused by hemodynamic stress because it was remote
      from the anastomosis and had developed after a prolonged interval of 14 years;
      furthermore, the aneurysm projected because of the hemodynamic force of the STA
      perfusion. CONCLUSION: This is the first reported case of a de novo MCA aneurysm
      that developed at a site remote from STA-MCA anastomosis because of hemodynamic
      force. Therefore, long-term control of blood pressure and repeated imaging
      examination should be performed to confirm patency and to identify aneurysm
      formation after STA-MCA bypass.

PMID- 22653395
TI  - The impact of standing regional cervical sagittal alignment on outcomes in
      posterior cervical fusion surgery.
AB  - BACKGROUND: Positive spinal regional and global sagittal malalignment has been
      repeatedly shown to correlate with pain and disability in thoracolumbar fusion.
      OBJECTIVE: To evaluate the relationship between regional cervical sagittal
      alignment and postoperative outcomes for patients receiving multilevel cervical
      posterior fusion. METHODS: From 2006 to 2010, 113 patients received multilevel
      posterior cervical fusion for cervical stenosis, myelopathy, and kyphosis.
      Radiographic measurements made at intermediate follow-up included the following:
      (1) C1-C2 lordosis, (2) C2-C7 lordosis, (3) C2-C7 sagittal vertical axis (C2-C7
      SVA; distance between C2 plumb line and C7), (4) center of gravity of head SVA
      (CGH-C7 SVA), and (5) C1-C7 SVA. Health-related quality-of-life measures included
      neck disability index (NDI), visual analog pain scale, and SF-36 physical
      component scores. Pearson product-moment correlation coefficients were calculated
      between pairs of radiographic measures and health-related quality-of-life scores.
      RESULTS: Both C2-C7 SVA and CGH-C7 SVA negatively correlated with SF-36 physical
      component scores (r = -0.43, P < .001 and r = -0.36, P = .005, respectively). C2
      C7 SVA positively correlated with NDI scores (r = 0.20, P = .036). C2-C7 SVA
      positively correlated with C1-C2 lordosis (r = 0.33, P = .001). For significant
      correlations between C2-C7 SVA and NDI scores, regression models predicted a
      threshold C2-C7 SVA value of approximately 40 mm, beyond which correlations were
      most significant. CONCLUSION: Our findings demonstrate that, similar to the
      thoracolumbar spine, the severity of disability increases with positive sagittal
      malalignment following surgical reconstruction.

PMID- 22653396
TI  - Magnetic resonance thermometry-guided laser-induced thermal therapy for
      intracranial neoplasms:  initial experience.
AB  - BACKGROUND: Laser-induced thermal therapy is a promising tool in the
      neurosurgeon's armamentarium. This methodology has seen a resurgence in
      application as a result of advances in technology. OBJECTIVE: To report our
      initial experience with the procedure after treating 20 consecutive patients, the
      largest series to date. METHODS: Patients were selected for laser therapy if they
      had failed conventional therapies, were unable to tolerate an open cranial
      procedure, or the tumor was deemed otherwise inoperable. In this series, 980-nm
      diode laser catheters were placed stereotactically in the operating room. The
      patients were then transferred to the magnetic resonance imaging suite for
      thermal ablation. RESULTS: A total of 31 laser applicators were placed in 20
      patients with intracranial neoplasms. The majority of patients (17 of 20) had
      prior treatment for their tumors. The overall accuracy of laser insertion was
      83.9%, improving with increased experience. The average lesion volume treated was
      7.0 +/- 9.0 cm2. With the use of damage estimates from the software provided, the
      treatment continued until the entire tumor had been irreversibly ablated. The
      average length of hospitalization was 2.27 days, with the majority of patients
      going home on postoperative day 1. Complications occurred in 4 patients,
      typically in those who were in poor health preoperatively. CONCLUSION: Laser
      induced thermal therapy is an intuitive procedure for treating difficult
      intracranial neoplasms. As with any other procedure, patient selection and lesion
      selection are important factors in determining outcome.

PMID- 22653397
TI  - Use of the da Vinci minimally invasive robotic system for resection of a
      complicated paraspinal schwannoma with thoracic extension: case report.
AB  - BACKGROUND AND IMPORTANCE: Applications of robotics to minimally invasive spine
      surgery have produced several benefits while sparing patients the morbidity of
      traditional open surgery. Minimally invasive spine surgery offers the advantages
      of less pain and less blood loss, along with quicker recovery and shorter
      hospital stays. The da Vinci robotic surgical system has recently been adapted to
      neurosurgical applications. This article details a posterior approach using a
      tubular retraction system in conjunction with an anterior approach using the da
      Vinci robot to completely remove large spinal schwannomas with intrathoracic
      extension. This technique is an example of a novel application of existing
      technology initially developed for other applications. CLINICAL PRESENTATION: Two
      patients with large thoracic schwannomas extending into the chest cavity are
      reviewed. We present images and video of the combined minimally invasive approach
      used to completely remove the lesions without complications. CONCLUSION: This
      report describes a novel neurosurgical application of an existing minimally
      invasive robotic surgical system.

PMID- 22653398
TI  - Factors and outcomes associated with early and delayed aneurysm treatment in
      subarachnoid hemorrhage patients in the United States.
AB  - BACKGROUND: Recent studies from selected centers have shown that early surgical
      treatment of aneurysms in subarachnoid hemorrhage (SAH) patients can improve
      outcomes. These results have not been validated in clinical practice at large.
      OBJECTIVE: To identify factors and outcomes associated with timing of ruptured
      intracranial aneurysm obliteration treatment in patients with SAH after
      hospitalization in the United States. METHODS: We analyzed the data from the
      Nationwide Inpatient Sample (2005-2008) for all patients presenting with primary
      diagnosis of SAH, receiving aneurysm treatment (endovascular coil embolization or
      surgical clip placement). Early treatment was defined as aneurysm treatment
      performed within 48 hours and delayed treatment if treatment was performed after
      48 hours of admission. RESULTS: Of 32 048 patients with SAH who underwent
      aneurysm treatment, 24 085 (75.2%) underwent early treatment and 7963 (24.8%)
      underwent delayed treatment. Female sex (P = .002), endovascular embolization (P
      < .001), and weekday admission (P < .001) were independent predictors of early
      treatment. In the early treatment group, patients were more likely discharged
      with none to minimal disability (odds ratio [OR] 1.30, 95% confidence interval
      [CI] 1.14-1.47) and less likely to be discharged with moderate to severe
      disability (OR 0.77, 95%CI 0.67-0.87) compared with those in the delayed
      treatment group. The in-hospital mortality was higher in the early treatment
      group compared with the delayed treatment group (OR 1.36 95%CI 1.12-1.66).
      CONCLUSION: Patients with SAH who undergo aneurysm treatment within 48 hours of
      hospital admission are more likely to be discharged with none to minimal
      disability. Early treatment is more likely to occur in those undergoing
      endovascular treatment and in patients admitted on weekdays.

PMID- 22653399
TI  - Involvement of Can f 5 in a case of human seminal plasma allergy.
AB  - BACKGROUND: The existence of IgE binding to dog dander extract without IgE
      antibodies against the described dog allergens (Can f 1, 2, 3 and 4) implies the
      presence of other dog allergens yet to be identified. Recently, an IgE-binding
      protein was isolated from dog urine and identified as prostatic kallikrein; it
      has been named Can f 5. Cross-reactivity between a dog dander allergen and human
      prostate-specific antigen (PSA) has been described. The aim of this study was to
      identify the dog dander allergen that presents cross-reactivity with PSA and
      demonstrate its clinical relevance in our patient with human seminal plasma
      allergy. METHODS: SDS-PAGE immunoblotting and inhibition tests were performed.
      Mass spectrometry was carried out to identify the protein involved in the allergy
      reactions. RESULTS: SDS-PAGE immunoblotting-inhibition with an IgE-binding
      protein from dog prostatic secretion showed total IgE binding inhibition to a 28
      kDa IgE-reactive band identified as PSA. The electroeluted protein from dog
      prostatic secretion was identified by mass spectrometry as Can f 5. IgE
      immunoblotting of human seminal plasma incubated with the serum of the patient
      revealed two IgE-binding bands (28 and 32.7 kDa). Both SDS-PAGE immunoblotting
      inhibition assays, with human seminal plasma or purified PSA in solid phase,
      showed complete IgE binding inhibition when the serum of the anaphylactic patient
      was preincubated with dog dander extract or recombinant Can f 5. CONCLUSIONS: The
      dog dander allergen that shows cross-reactivity with human PSA has been
      characterized and turns out to be the recently described Can f 5. We demonstrated
      the clinical relevance of this cross-reactivity in a patient.

PMID- 22653400
TI  - Second-year Italian medical students' attitudes toward care of the dying patient:
      an exploratory study.
AB  - To our knowledge, no other study has investigated Italian medical students'
      attitudes toward care of the dying patient. The purpose of this study is to
      investigate those attitudes among second-year Italian medical students. Two
      hundred students completed the Italian version of the Frommelt Attitude Toward
      Care of the Dying Scale form B (FATCOD Form B). Students obtained a mean total
      score on FATCOD Form B of 112.8 (the possible total score ranges from 30 to 150).
      On some items, statistically significant differences (p < 0.05) emerged for
      gender and personal previous experiences with terminally ill people. This study
      shows poor attitudes toward care of the dying patient among second-year Italian
      medical students, as measured by FATCOD Form B. The need to establish tailored
      methods in End-of-Life Care education to make students aware of their
      relationship patterns and to improve students' attitudes toward dying patients is
      discussed.

PMID- 22653406
TI  - The Swiss report on homeopathy: a case study of research misconduct.

PMID- 22653407
TI  - Internal validity and the risk of bias: a case for a comprehensive review.

PMID- 22653409
TI  - Could chemical enhancement of gold nanoparticle penetration be extrapolated from
      established approaches for drug permeation?
AB  - BACKGROUND AND AIM: Investigations on chemical enhancement of skin penetration of
      gold nanoparticles are considered crucial to have a deeper insight into the main
      barrier of particle penetration. METHODS: In this study, penetration of gold
      nanoparticles in the presence of several chemical enhancers - urea, sodium lauryl
      sulphate, polysorbate 80 and dimethyl sulfoxide (DMSO) - through human skin was
      studied. RESULTS: Among the tested chemical enhancers, DMSO could induce the
      penetration of hydrophilic (citrate-stabilized) gold colloid of no intrinsic
      penetration ability in a concentration-dependent manner. Pretreatment of the skin
      with DMSO however reduced the penetration of hydrophobic (cetrimide-coated) gold
      nanoparticles as a result of aggregation in the top layers of the stratum corneum
      limiting penetration into the deeper skin layers. In addition, nanoparticles
      vehicle interaction and the stability of the nanoparticles in the applied vehicle
      were found important determinants of skin penetration. CONCLUSION: Our results
      demonstrate that the already established approaches for chemical permeation
      enhancement of drug molecules and their postulated mechanisms could be used as
      preliminary guidelines for enhancing the penetration of nanoparticles. At this
      size range of 15 nm, intercellular lipids provide the main barrier to particle
      penetration through the stratum corneum.

PMID- 22653414
TI  - Cooperation between metal and ligand in oxygen atom transport by N-confused
      porphyrin oxorhenium(V) complexes.
AB  - N-Confused porphyrin oxorhenium(V) complexes were prepared and their X-ray
      structures were elucidated. The oxorhenium(V) complexes can transfer oxygen atom
      from pyridine N-oxide to triphenylphosphine, in which unique cooperation between
      metal and ligand was observed.

PMID- 22653415
TI  - Congestive heart failure: who is likely to be readmitted?
AB  - Readmission for congestive heart failure (CHF) is the most common reason for
      readmission among Medicare fee-for-service patients. Yet CHF readmissions are not
      just a Medicare problem. This study examined who is likely to be readmitted for
      CHF, using all-payer hospital discharges from 14 of the states participating in
      the Healthcare Cost and Utilization Project. Patients with the strongest positive
      association with readmission were discharged against medical advice, covered by
      Medicaid, and had more severe loss of function and certain comorbidities such as
      drug abuse, renal failure, or psychoses. Weak negative relationship between
      readmission and cost of index admission provides some evidence that hospitals
      with higher readmission rates do not systematically use fewer resources in
      treating patients in initial encounters. High readmission rate for Medicaid
      patients suggests that state and federal governments should target Medicaid
      populations and drug abuse treatment for better care coordination to reduce
      readmissions and health care costs.

PMID- 22653416
TI  - Does a large-scale organizational transformation toward patient-centered access
      change the utilization and costs of care for patients with diabetes?
AB  - The authors examined whether Group Health's Access Initiative changed the
      utilization and costs of care among enrollees with diabetes. Using a single (one
      group) interrupted time series design, repeated-measures generalized estimating
      equation models were used to estimate changes in utilization and costs during the
      Initiative rollout (2002-2003) and to compare the slopes (annual rates of change)
      for utilization and costs during the Pre-Initiative period (1998-2002) to the
      slopes during Full-Implementation (2003-2006) among 9,871 members continuously
      enrolled from 1997 to 2006 with type 1 or 2 diabetes. Total costs increased in
      Full-Implementation, but the annual change in total costs did not change. Primary
      care visits declined, but primary care contacts grew, largely from the
      Initiative's introduction of secure messaging. Specialty visits did not change;
      however, the Initiative may have increased emergency visits. To reduce emergency
      visits, future access initiatives should include proactive and comprehensive
      outpatient care for patients with diabetes.

PMID- 22653417
TI  - Various phosphodiesterase activities in different regions of the heart alter the
      cardiac effects of nitric oxide.
AB  - The modulation of cardiac functions by nitric oxide (NO) was established. This
      study examined the influences of phosphodiesterase (PDE) inhibitors on the action
      of NO in the different regions of the rat heart. NO donor diethylamine nonoate
      (DEA/NO) (0.1-100 MUM) decreased functions of the right atrium. DEA/NO-induced
      depression of the developed tension of the right atrium was inhibited by [erythro
      9-(2-hydroxy-3-nonyl)adenine] (PDE2 inhibitor), augmented by milrinone (PDE3
      inhibitor), and upturned by rolipram (PDE4 inhibitor). A DEA/NO-induced decrease
      in the resting tension was inhibited by vinpocetine (PDE1 inhibitor) and [erythro
      9-(2-hydroxy-3-nonyl)adenine] but reversed by rolipram. The decreased sinus rate
      by DEA/NO was prevented by vinpocetine and rolipram. DEA/NO increased cyclic
      guanosine monophosphate and cyclic adenosine monophosphate (cAMP) concentrations
      in the right atrium, and rolipram enhanced increased cAMP level. DEA/NO had no
      effect on the contraction of the papillary muscle. However, unchanged contraction
      under DEA/NO stimulation was decreased by vinpocetine, milrinone, and rolipram.
      DEA/NO increased cyclic guanosine monophosphate concentration but has no effect
      on cAMP in the papillary muscle. However, in the presence of vinpocetine and
      milrinone, DEA/NO reduced cAMP level. The PDE5 inhibitor sildenafil has no effect
      on DEA/NO actions. This study indicates that a variety of PDE activities in
      different regions of the rat heart shapes the action of NO on the myocardium.

PMID- 22653418
TI  - Modeling hereditary cardiac disease with patient-specific-induced pluripotent
      stem cells: opportunities and concerns.

PMID- 22653419
TI  - The effects of poloxamer-188 on left ventricular function in chronic heart
      failure after myocardial infarction.
AB  - BACKGROUND: Poloxamer-188 (P-188) is a biological membrane sealant that prevents
      the unregulated entry of Ca into cardiomyocytes and has been shown to have the
      ability to act as a membrane-repair agent in isolated cardiac myocytes. The
      purpose of this study was to determine if treatment with P-188 would improve left
      ventricular (LV) function in a rat chronic heart failure (CHF) model. METHODS: We
      ligated the left coronary artery of adult male Sprague-Dawley rats to induce a
      myocardial infarction (MI). The rats were allowed to recover for 8 weeks until
      stable CHF was present and treated with a range of P-188 doses [1.5 mg/kg (N =
      6), 4.6 mg/kg (N = 11), 15.3 mg/kg (N = 11), and 460 mg/kg (N = 6)] delivered via
      30 minutes of intravenous infusion. The rats were randomized to study groups:
      control, 2 hours, 24 hours, 48 hours, 1 week, and 2 weeks posttreatment (N = 8 in
      each group). RESULTS: Two weeks after high dose (460 mg/kg) administration, P-188
      improved (P < 0.05) left ventricular ejection fraction from 34% to 51%, which
      persisted over 38 hours and decreased (P < 0.05) LV end systolic diameter from
      0.9 +/- 0.07 to 0.6 +/- 0.08 cm, in the rats with CHF. There was no statistical
      change in hemodynamics. Additionally, P-188 reduced (P < 0.05) circulating
      troponin levels 2 weeks after treatment. CONCLUSIONS: Treatment with P-188
      improves the LV function and partially reverses maladaptive LV remodeling in rats
      with moderate CHF after MI. These data introduce the idea of using a biological
      membrane sealant as a new approach to treating CHF after MI.

PMID- 22653420
TI  - Regulation of autophagy in the heart in health and disease.

PMID- 22653421
TI  - Larval abundance and its relation to macrofouling settlement pattern in the
      coastal waters of Kalpakkam, southeastern part of India.
AB  - The present work revealed that salinity, water temperature, and food availability
      were the most crucial factors affecting the abundance of larvae and their
      settlement as macrofouling community in the coastal waters of Kalpakkam.
      Quantitative as well as qualitative results showed that late post-monsoon (April
      May) and pre-monsoon (June-September) periods were found to be suitable periods
      for larval growth, development, and survival to adult stages for most of the
      organisms. Clustering of physico-chemical and biological (including larval and
      adult availability) data yielded two major clusters; one formed by northeast (NE)
      monsoon months (October-January) and the other by post-monsoon/summer (February
      May) months, whereas; pre-monsoon months (June-September) were distributed
      between these two clusters. Among all the major macrofouler groups, only bivalves
      established a successful relationship between its larval abundance and adult
      settlement. Principal component analysis indicated good associations of bivalve
      larvae with polychaete larvae and adult bivalves with adult barnacles. However,
      biotic relation between ascidians and bryozoans was observed both in the larval
      as well as adult community.

PMID- 22653422
TI  - One-dimensional mean computed tomography value evaluation of ground-glass opacity
      on high-resolution images.
AB  - OBJECTIVE: Differentiation of atypical adenomatous hyperplasia (AAH),
      bronchioloalveolar carcinoma (BAC), and invasive carcinoma on computed tomography
      (CT) is useful for determining "follow-up or resection" strategies for lesions
      displaying ground-glass opacity (GGO). The purpose of this study is to evaluate
      one-dimensional quantitative CT values of GGO on high-resolution CT (HRCT) images
      using computer-aided diagnosis. METHODS: Between April 2001 and March 2010, a
      total of 44 nodules in 42 patients with pure or mixed GGOs <=2 cm were
      retrospectively evaluated. Maximum diameter and one-dimensional mean CT (m-CT)
      value of the diameter were measured using a computer graphics support system
      (HOPE/DrABLE-EX, Fujitsu, Tokyo, Japan) that displays a CT density profile across
      the tumor. RESULTS: m-CT values were -682 +/- 64 HU (range) for AAH lesions, -544
      +/- 179 (range) for Type A lesions, -496 +/- 147 (range) for Type B lesions, and 
      371 +/- 142 (range) for invasive lesions. AAH lesions had a significantly lower m
      CT value than Type B lesions. AAH, Type A, and Type B lesions had significantly
      lower m-CT values than invasive lesions (p < 0.05). All seven GGO lesions with a
      maximum diameter <=1 cm and m-CT value <=-600 HU were pre-invasive lesions, while
      16 of 22 (73 %) cases with maximum diameter >1 cm and m-CT value >-600 HU were
      invasive lesions. CONCLUSION: Observation may be indicated for GGO lesions with a
      maximum diameter <=1 cm and m-CT value <=-600 HU.

PMID- 22653423
TI  - Flow injection chemiluminescence sensor using core-shell molecularly imprinted
      polymers as recognition element for determination of dapsone.
AB  - This paper reports the preparation of dapsone (DDS) imprinted polymer layer
      coated silica submicron particles (SiO(2)) combined with chemiluminescence (CL)
      toward analysis of tracing DDS in practical samples. To induce the selective
      occurrence of surface polymerization, the amino groups were first grafted at the
      surface of SiO(2) by the (3-aminopropyl)triethoxysilane (APTES). The molecularly
      imprinted polymers (MIP) were coated at the surface of modified SiO(2) by the
      graft copolymerization. After the removal of templates, recognition sites of DDS
      were exposed in the polymer layers. The DDS-imprinted products were characterized
      by FT-IR, SEM, TEM, dynamic adsorption, and static adsorption tests. The
      proximity between the thickness of MIP layer and the spatial size of DDS
      indicated that the imprinted sites almost situated at the surface of MIP, leading
      to rapid adsorption saturation within 90 min. The apparent maximum binding amount
      of MIP toward DDS was evaluated as 14.98 mg.g(-1), which was much higher than
      that of non-molecularly imprinted polymers. The CL sensor provided a wide linear
      range for DDS within 1.0 * 10(-6) to 1.0 * 10(-4) mol.L(-1) with a detection
      limit of 5.27 * 10(-7) mol.L(-1) and the relative standard deviation of 1.8 % (n
      = 11) by determinations of 5.0 * 10(-6) mol.L(-1) DDS. This method was applied to
      determine DDS in urine samples and satisfactory results were obtained.

PMID- 22653424
TI  - DNA methylation-specific multiplex assays for body fluid identification.
AB  - Recent advances in whole-genome epigenetic analysis indicate that chromosome
      segments called tissue-specific differentially methylated regions (tDMRs) show
      different DNA methylation profiles according to cell or tissue type. Therefore,
      body fluid-specific differential DNA methylation is a promising indicator for
      body fluid identification. However, DNA methylation patterns are susceptible to
      change in response to environmental factors and aging. Therefore, we investigated
      age-related methylation changes in semen-specific tDMRs using body fluids from
      young and elderly men. After confirming the stability of the body fluid-specific
      DNA methylation profile over time, two different multiplex PCR systems were
      constructed using methylation-sensitive restriction enzyme PCR and methylation
      SNaPshot, in order to analyze the methylation status of specific CpG sites from
      the USP49, DACT1, PRMT2, and PFN3 tDMRs. Both multiplex systems could
      successfully identify semen with spermatozoa and could differentiate menstrual
      blood and vaginal fluids from blood and saliva. Although including more markers
      for body fluid identification might be necessary, this study adds to the support
      that body fluid identification by DNA methylation profiles could be a valuable
      tool for forensic analysis of body fluids.

PMID- 22653425
TI  - Controlled human exposures to diesel exhaust.
AB  - Diesel exhaust is a complex mixture of gaseous and particulate compounds
      resulting from an incomplete combustion of diesel fuel. Controlled human
      exposures to diesel exhaust and diesel exhaust particles (DEP) have contributed
      to understanding health effects. Such acute exposure studies of healthy subjects
      to diesel exhaust and DEP demonstrate a pro-inflammatory effect in the lung and
      systemically but only at higher concentrations (with a threshold dose
      approximating 300 ug/m3). Unexpectedly, there appears to be a lack of an
      inflammatory response to diesel exhaust and DEP in asthmatic individuals.
      Controlled human exposure studies of cardiovascular effects show that, comparable
      to other particle-associated exposures, diesel exhaust has a capacity to
      precipitate coronary artery disease. In addition, there is a relationship between
      diesel exhaust and DEP exposure and vascular endpoints; these effects in diesel
      exhaust may be diminished with removal of DEP. Many extra-pulmonary health
      effects of diesel exhaust exposure, including systemic inflammation, pro
      thrombotic changes, and cardiovascular disease, are considered consequent to pro
      inflammatory events and inflammation in the lung. Future research will focus on
      the relative importance of diesel exhaust components, potential interactions
      between components and other pollutants, effects in sensitive individuals, and
      effects of longer or repeated exposures.

PMID- 22653427
TI  - Surgeons and scientists: symbiosis in spinal research?

PMID- 22653426
TI  - Crystal structure of kindlin-2 PH domain reveals a conformational transition for
      its membrane anchoring and regulation of integrin activation.
AB  - Kindlin-2 belongs to a subfamily of FERM domain containing proteins, which plays
      key roles in activating integrin transmembrane receptors and mediating cell
      adhesion. Compared to conventional FERM domains, kindlin-2 FERM contains an
      inserted pleckstrin homology (PH) domain that specifically binds to
      phosphatidylinositol (3,4,5) trisphosphate (PIP3) and regulates the kindlin-2
      function. We have determined the crystal structure of kindlin-2 PH domain at 1.9
      A resolution, which reveals a conserved PH domain fold with a highly charged and
      open binding pocket for PIP3 head group. Structural comparison with a previously
      reported solution structure of kindlin-2 PH domain bound to PIP3 head group
      reveals that upon PIP3 insertion, there is a significant conformational change of
      both the highly positively charged loop at the entry of the PIP3 binding pocket
      and the entire beta barrel of the PH domain. We propose that such "induced-fit"
      type change is crucial for the tight binding of PIP3 to anchor kindlin-2 onto the
      membrane surface, thereby promoting its binding to integrins. Our results provide
      important structural insight into kindlin-2-mediated membrane anchoring and
      integrin activation.

PMID- 22653429
TI  - Fall prevention through patient partnerships.
AB  - Falls in community-dwelling older adults are often preventable, yet remain the
      leading cause of deaths due to injury and a major cost to the healthcare system.
      Primary care nurse practitioners who care for older adults can minimize the risk
      for falls by using specific assessment and prevention strategies.

PMID- 22653430
TI  - Strategies to increase colorectal cancer screening.
AB  - Colorectal cancer screening (CRCS) is the only way to detect colorectal cancer in
      its earlier stages when morbidity and mortality are low. The literature has shown
      provider-directed recommendations with office system-directed interventions are
      the best way to increase CRCS rates.

PMID- 22653431
TI  - Amelogenin enhances the osteogenic differentiation of mesenchymal stem cells
      derived from bone marrow.
AB  - Amelogenins are the major constituent of developing extracellular enamel matrix
      proteins and are understood to have an exclusively epithelial origin. Recent
      studies have demonstrated that amelogenins can be detected in other tissues,
      including bone marrow mesenchymal stem cells (MSCs), but the role of amelogenins
      in MSCs remains unclear. The purpose of this study was to examine the effect of
      recombinant human full-length amelogenin (rh174) on the osteogenic
      differentiation of cultured human MSCs. MSCs isolated from human bone marrow were
      cultured in osteoblastic differentiation medium with 0, 10 or 100 ng/ml rh174.
      The mRNA levels of bone markers were examined by real-time PCR analysis. Alkaline
      phosphatase (ALP) activity and calcium concentration were determined.
      Mineralization was evaluated by alizarin red staining. The mRNA levels of ALP,
      type I collagen, osteopontin and bone sialoprotein in the MSCs treated with rh174
      became significantly higher than those in non-treated controls. Treatment of MSCs
      with rh174 also enhanced ALP activity and calcium concentration, resulting in
      enhanced mineralization, as denoted by high intensity of alizarin red staining.
      In conclusion, the present study showed that rh174 enhances the mineralization
      accompanied by the upregulation of bone markers in human bone marrow MSCs during
      osteogenic differentiation, suggesting a certain role of amelogenin in the
      modulation of osteogenic differentiation of MSCs.

PMID- 22653437
TI  - Characterisation of energy response of Al(2)O(3):C optically stimulated
      luminescent dosemeters (OSLDs) using cavity theory.
AB  - Aluminium oxide (Al(2)O(3):C) is a common material used in optically stimulated
      luminescent dosemeters (OSLDs). OSLDs have a known energy dependence, which can
      impact on the accuracy of dose measurements, especially for lower photon
      energies, where the dosemeter can overrespond by a factor of 3-4. The purpose of
      this work was to characterise the response of Al(2)O(3):C using cavity theory and
      to evaluate the applicability of this approach for polyenergetic photon beams.
      The cavity theory energy response showed good agreement (within 2 %) with the
      corresponding measured values. A comparison with measured values reported in the
      literature for low-energy polyenergetic spectra showed more varied agreement
      (within 6 % on average). The discrepancy between these results is attributed to
      differences in the raw photon energy spectra used to calculate the energy
      response. Analysis of the impact of the photon energy spectra versus the mean
      photon energy showed improved accuracy if the energy response was determined
      using the entire photon spectrum rather than the mean photon energy. If not
      accounted for, the overresponse due to photon energy could introduce substantial
      inaccuracy in dose measurement using OSLDs, and the results of this study
      indicate that cavity theory may be used to determine the response with reasonable
      accuracy.

PMID- 22653438
TI  - Safety assessment by multiphoton fluorescence/second harmonic generation/hyper
      Rayleigh scattering tomography of ZnO nanoparticles used in cosmetic products.
AB  - Zinc oxide nanoparticles (ZnO NPs) are commonly used as UV filters in commercial
      sunscreen products. Their penetration into the skin is intensively discussed in
      the literature. In the present in vivo study, penetration of ZnO NPs (30 nm in
      size) into human skin was investigated by multiphoton tomography. Based on the
      non-linear effects of a second harmonic generation and hyper-Rayleigh scattering,
      the distribution of ZnO NPs in the horny layers of the epidermis, as well as the
      furrows, wrinkles and orifice of the hair follicles was analyzed. This method
      permitted distinguishing between the particulate and dissolved forms of Zn. A
      detection limit of 0.08 fg/MUm(3) was estimated. Taking advantage of this
      sensitivity, it was clearly shown that ZnO NPs penetrate only into the outermost
      layers of stratum corneum, furrows and into the orifices of the hair follicles
      and do not reach the viable epidermis.

PMID- 22653439
TI  - Spectral-domain optical coherence tomography (SD-OCT) patterns and response to
      intravitreal bevacizumab therapy in macular edema associated with branch retinal
      vein occlusion.
AB  - BACKGROUND: To evaluate the baseline spectral-domain optical coherence tomography
      (SD-OCT) characteristics of macular edema (ME) due to branch retinal vein
      occlusion (BRVO) for visual outcome after intravitreal bevacizumab injection.
      METHODS: Fifty-nine patients treated in one eye with intravitreal bevacizumab for
      ME due to BRVO were retrospectively reviewed. Stepwise multiple regression
      analysis was used to evaluate the relative contribution of several variables,
      including SD-OCT characteristics such as photoreceptor inner segment/outer
      segment (IS/OS) integrity and external limiting membrane (ELM status), baseline
      best-corrected visual acuity (BCVA), and baseline central retinal thickness (CRT)
      with final visual outcome. RESULTS: Thirty-one patients (52.5 %) had disrupted
      photoreceptor IS/OS integrity. The mean BCVA improved significantly from 0.50
      logMAR (20/63 Snellen equivalent) to 0.10 logMAR (20/25 Snellen equivalent) in
      the intact photoreceptor group (p = 0.000, paired t-test). However, the mean BCVA
      was improved in the disrupted photoreceptor group, from 1.10 logMAR (20/252
      Snellen equivalent) to 0.94 logMAR (20/174 Snellen equivalent), which was not
      statistically significant (p = 0.177, paired t-test). ELM was disrupted in 23
      patients (39.0 %). The mean BCVA improved significantly from 0.63 logMAR (20/85
      Snellen equivalent) to 0.26 logMAR (20/36 Snellen equivalent) in the intact ELM
      group (p = 0.000, paired t-test), however, not significantly improved in the
      disrupted ELM group, from 1.09 logMAR (20/246 Snellen equivalent) to 1.01 logMAR
      (20/205 Snellen equivalent) (p = 0.563, paired t-test). The strongest individual
      predictor of final BCVA among patients with ME due to BRVO was the integrity of
      photoreceptor IS/OS layer on SD OCT (r (2) = 0.514, p = 0.000, stepwise multiple
      regression), but the most efficient model was the combination of the
      photoreceptor IS/OS integrity, ELM status, and baseline BCVA (r(2) = 0.671, p =
      0.000, stepwise multiple regression). The strongest predictor of final BCVA was
      the status of photoreceptor IS/OS integrity (beta = 0.532, p = 0.000, stepwise
      multiple regression), followed by ELM status (beta = 0.325, p = 0.006, stepwise
      multiple regression), and the baseline BCVA (beta = 0.238, p = 0.013, stepwise
      multiple regression). CONCLUSION: Our results suggest that baseline SD-OCT
      characteristics, the status of photoreceptor IS/OS and ELM can be helpful in
      predicting the final visual outcome after intravitreal bevacizumab injection in
      these patients.

PMID- 22653440
TI  - Evaluation of myopic corneal diameter with the Orbscan II Topography System.
AB  - BACKGROUND: To assess the myopic corneal diameter with Orbscan II Topography
      System (Bausch & Lomb, Orbtek Inc., Salt Lake City, UT, USA). METHODS: Four
      hundred sixty-two eyes of 231 myopic patients and 129 emmetropic eyes were
      measured with the Orbscan II system. Eyes were divided into four groups according
      to the spherical equivalent(SE) as follows: group 1 [emmetropic group, spherical
      equivalents between -0.50 D and +0.50 D (-0.50<SE <= +0.50)]; group 2 [low myopia
      group, spherical equivalent between -0.50 D and -3.00D (-3.00<SE <= -0.50)];
      group 3 [median myopia group, spherical equivalent between -3.00 and -6.00D (
      6.00<SE <= -3.00)]; and group 4 [high myopia group, spherical equivalents of 
      6.00D or less (<=-6.00)]. Manifest refraction results and the Orbscan II corneal
      topographic maps were reviewed retrospectively. Horizontal corneal diameters
      (white-to-white [WTW] distance) were measured with the Orbscan II system.
      Subjects in different groups were matched to be comparable in terms of spherical
      equivalents. RESULTS: The corneal diameter in all myopic eyes was 11.49 +/- 0.36
      mm. There were no significant differences between right and left eyes in the t
      test for paired samples (t = -0.119, P = 0.906). Differences among four groups
      proved to be significant in the ANOVA (F = 4.487, P = 0.004). CONCLUSIONS: This
      article provides a detailed description and analysis of Orbscan II corneal
      diameter of a normal myopic population. High degree of mirror image symmetry
      existed in myopic corneal diameter. Spherical equivalents made a difference in
      corneal diameter.

PMID- 22653441
TI  - Group I and II mammalian PAKs have different modes of activation by Cdc42.
AB  - p21-activated kinases (PAKs) are Cdc42 effectors found in metazoans, fungi and
      protozoa. They are subdivided into PAK1-like (group I) or PAK4-like (group II)
      kinases. Human PAK4 is widely expressed and its regulatory mechanism is unknown.
      We show that PAK4 is strongly inhibited by a newly identified auto-inhibitory
      domain (AID) formed by amino acids 20 to 68, which is evolutionarily related to
      that of other PAKs. In contrast to group I kinases, PAK4 is constitutively
      phosphorylated on Ser 474 in the activation loop, but held in an inactive state
      until Cdc42 binding. Thus, group II PAKs are regulated through conformational
      changes in the AID rather than A-loop phosphorylation.

PMID- 22653442
TI  - Adaptive governance of synthetic biology.

PMID- 22653443
TI  - Mutant p53 interactome identifies nardilysin as a p53R273H-specific binding
      partner that promotes invasion.
AB  - The invasiveness of tumour cells depends on changes in cell shape, polarity and
      migration. Mutant p53 induces enhanced tumour metastasis in mice, and human cells
      overexpressing p53R273H have aberrant polarity and increased invasiveness,
      demonstrating the 'gain of function' of mutant p53 in carcinogenesis. We
      hypothesize that p53R273H interacts with mutant p53-specific binding partners
      that control polarity, migration or invasion. Here we analyze the p53R273H
      interactome using stable isotope labelling by amino acids in cell culture and
      quantitative mass spectrometry, and identify at least 15 new potential mutant p53
      specific binding partners. The interaction of p53R273H with one of them-
      nardilysin (NRD1)--promotes an invasive response to heparin binding-epidermal
      growth factor-like growth factor that is p53R273H-dependant but does not require
      Rab coupling protein or p63. Advanced proteomics has thus allowed the detection
      of a new mechanism of p53-driven invasion.

PMID- 22653445
TI  - Total aortic arch replacement with a novel four-branched frozen elephant trunk
      graft: first-in-man results.
AB  - OBJECTIVES: The combined disease of the aortic arch and the proximal descending
      aorta remains a surgical challenge. With the 'frozen elephant technique', the
      ascending aorta, along with the aortic arch, is replaced conventionally and an
      endovascular stent graft is placed into the descending aorta in the antegrade
      manner through the open aortic arch, thereby potentially allowing for a 'single
      stage' operation. The purpose of this study was to assess the feasibility of a
      novel four-branched hybrid graft (Vascutek, Scotland). METHODS: From April 2010
      to August 2011, 34 patients (25 males, age 60 +/- 14 years) were operated on [14
      aneurysms, 20 dissections (18 acute)]. Ten of these patients had undergone
      previous cardiac operations. The collapsed endoprosthesis was deployed in the
      descending aorta through the opened aortic arch. A sewing collar between the
      graft segments simplified the 'distal' anastomosis. The four-branched graft
      segment allowed the replacement of the aortic arch and supra-aortic vessels
      individually. Concomitant procedures were performed if necessary. RESULTS: There
      were three deaths within the 30 postoperative days. All of them were of AADA
      patients. The mean cardiopulmonary bypass time was 254 +/- 53 min, aortic cross
      clamp time was 148 +/- 48 min and circulatory arrest time was 48 +/- 22 min.
      Aortic valve-sparing root surgery was performed in 12 patients, Bentall procedure
      in four, CABG in three and mitral valve repair in two. In one patient, a
      secondary endovascular extension of the stent graft was necessary to reach the
      landing zone. In all others, postoperative CT-Scans confirmed the desired
      results. CONCLUSIONS: The graft adds to the 'frozen elephant trunk' concept for
      treating the arch and proximal descending aorta. Early experience demonstrates an
      excellent 30-day survival. Combining the frozen elephant with a four-branched
      arch graft increases the armament of the surgeon in the treatment of complex and
      diverse aortic arch pathology.

PMID- 22653446
TI  - Surgical treatment of right ventricular outflow tract obstruction after Tetralogy
      of Fallot {S,D,I} repair.
AB  - Situs solitus of viscera and atria, D-looped ventricle with atrioventricular
      concordance, and inverted normally related great arteries with ventriculoarterial
      concordance characterize the segmental anatomy of an extremely rare {S,D,I}
      variant of Tetralogy of Fallot. The main pulmonary artery is rightward of the
      aorta and the right coronary artery crosses over the right ventricular outflow
      tract from left to right to reach the right atrioventricular groove. Our patient
      had undergone a neonatal repair due to persistent cyanosis with the implantation
      of a pericardial infundibular patch after the diagnosis of Tetralogy of Fallot
      {S,D,I}. He presented with an annular right ventricular outflow tract obstruction
      at 19 months of age. We describe the surgical approach employing a transannular
      patch implantation for the relief of the annular right ventricular outflow tract
      obstruction.

PMID- 22653444
TI  - The base of the cilium: roles for transition fibres and the transition zone in
      ciliary formation, maintenance and compartmentalization.
AB  - Both the basal body and the microtubule-based axoneme it nucleates have
      evolutionarily conserved subdomains crucial for cilium biogenesis, function and
      maintenance. Here, we focus on two conspicuous but underappreciated regions of
      these structures that make membrane connections. One is the basal body distal
      end, which includes transition fibres of largely undefined composition that link
      to the base of the ciliary membrane. Transition fibres seem to serve as docking
      sites for intraflagellar transport particles, which move proteins within the
      ciliary compartment and are required for cilium biogenesis and sustained
      function. The other is the proximal-most region of the axoneme, termed the
      transition zone, which is characterized by Y-shaped linkers that span from the
      axoneme to the ciliary necklace on the membrane surface. The transition zone
      comprises a growing number of ciliopathy proteins that function as modular
      components of a ciliary gate. This gate, which forms early during ciliogenesis,
      might function in part by regulating intraflagellar transport. Together with a
      recently described septin ring diffusion barrier at the ciliary base, the
      transition fibres and transition zone deserve attention for their varied roles in
      forming functional ciliary compartments.

PMID- 22653447
TI  - A rare cause of chest pain: a partial congenital absence of the pericardium.

PMID- 22653448
TI  - Extended mild hypothermic aortic surgery.

PMID- 22653449
TI  - Endosis and exosis: new names for fusion and budding.

PMID- 22653450
TI  - Application of Pediatric Appendicitis Score on the emergency department of a
      secondary level hospital.
AB  - BACKGROUND: Acute appendicitis is the most common surgical emergency during
      childhood. Accurate early diagnosis is important to avoid complications and
      unnecessary interventions. In 2002, Samuel developed the Pediatric Appendicitis
      Score (PAS) based on a series of data obtained from anamnesis, physical
      examination, and laboratory tests. The main purpose of this study was to check
      the validity of PAS and its applicability to our population. METHODS: Prospective
      observational study, carried out at Hospital Rio Hortega (Valladolid, Spain),
      between June 2009 and May 2010. Data from 101 patients who presented to the
      emergency department experiencing abdominal pains were recovered. RESULTS: A
      total of 101 patients were included in the study: 55 were boys and 46 girls. The
      mean age was 9.51 (2.76) years. Diagnosis was acute appendicitis in 28 patients,
      adenitis in 8 patients, nonspecific abdominal pain in 51 patients, and other
      diagnoses in 14 patients. The mean (SD) PAS for children with and without
      appendicitis was 7.43 (1.79) and 4.97 (1.67), respectively (P < 0.001).
      CONCLUSIONS: With a cutoff PAS of 3 or lower, there were no patients diagnosed
      with acute appendicitis; hence, these patients could be discharged without any
      image studies. If all the patients with a PAS of 8 or higher undergo surgery, we
      would find in our sample a 4.95% rate of negative appendicectomy, less than other
      studies have shown. The application of this score in the emergency department
      could help in the decision making process, aiding in the identification of
      patients with a low risk of having appendicitis and enabling a better use of
      resources by avoiding unnecessary diagnostic tests.

PMID- 22653451
TI  - Obesity screening in the pediatric emergency department.
AB  - OBJECTIVES: The purposes of this study were (1) to examine parental perception of
      childhood obesity and race with measured body mass index (BMI), (2) to determine
      if parents are receptive to obesity screening in the pediatric emergency
      department and if receptivity varies by race or weight status, and (3) to
      determine eating habits that are predictors of obesity. METHODS: This study is a
      cross-sectional study, with a convenience sample of 213 patients (aged 4-16 years
      accompanied by a parent/legal guardian to a pediatric emergency department).
      Weight and height were obtained, and parents were asked to complete a survey
      about perception of their child's weight, nutrition, and exercise habits.
      RESULTS: The current study found that parent perception of weight status was
      fairly accurate, and perception was predictive of BMI. Race, however, was not
      predictive of BMI. Parents were generally receptive of weight screening in the
      pediatric emergency department, and this did not vary as a function of weight
      status; however, receptivity did vary based on ethnicity, with African American
      parents being more receptive than white parents. Large portion sizes and the
      number of times a child eats fast food per week were found to be predictive of
      obesity. CONCLUSIONS: Greater than half of the children presenting to our
      pediatric emergency department were overweight or obese. Parents were generally
      accurate in their perception of their child's weight but were still receptive to
      obesity prevention and screening in the pediatric emergency department.

PMID- 22653452
TI  - Internet access and electronic communication among families in an urban pediatric
      emergency department.
AB  - BACKGROUND: The Internet may represent an opportunity for health care providers
      in the emergency department (ED) to deliver discharge instructions and after-care
      educational materials electronically to patients and their caregivers.
      OBJECTIVES: The objectives of this study were to determine the prevalence of
      Internet access and use among caregivers of children who visit the ED and to
      evaluate their interest in receiving after-care communication and educational
      material electronically. METHODS: We distributed a self-administered survey to a
      convenience sample of English-speaking caregivers of children who presented to
      the ED of an urban, academic, pediatric hospital during November and December
      2009. RESULTS: The survey was distributed to and completed by 509 English
      speaking respondents. Of the participants, 423 (83.1%) of 509 identified
      themselves as black/African American, and 397 (77.9%) of 509 were publicly
      insured. Of the participants, 503 of 509 (98.9%; 95% confidence interval [CI],
      97.9%-99.8%) reported that they have access to the Internet. Of the participants
      with Internet access, 312 of 503 (62.0%; 95% CI, 57.8%-66.3%) have access at
      home, 166 of 503 (33.0%; 95% CI, 28.9%-33.1%) have access at work, and 112 of 503
      (22.3%; 95% CI, 18.6%-25.9%) have access by mobile phone. When asked about
      electronic communication and social networking, 483 of 503 (96.0%; 95% CI, 94.3%
      97.7%) have an e-mail account, and 304 of 503 (60.4%; 95% CI, 56.2%-64.7%) have a
      Facebook account. Furthermore, 353 of 503 (70.1%; 95% CI, 66.2%-74.2%) reported
      accessing the Internet daily, whereas 128 of 503 (25.4%; 95% CI, 21.6%-29.3%)
      access the Internet at least 2 to 6 times per week. Among all respondents,
      interest in receiving communication from the ED only electronically was expressed
      by 259 of 509 participants (50.9%; 95% CI, 46.5%-55.2%). Approximately one third
      of the participants (173/509 [34%; 95% CI, 29.9%-38.1%]) expressed interest in an
      electronic channel for communication between the ED and their child's patient
      primary care provider. CONCLUSIONS: In this predominantly minority and
      economically disadvantaged population of caregivers presenting to an urban
      pediatric ED, a large majority reported regular access to the Internet and
      willingness and ability to receive communication from the ED via electronic
      means.

PMID- 22653453
TI  - Weighing the pediatric patient during trauma resuscitation and its concordance
      with estimated weight using Broselow Luten Emergency Tape.
AB  - OBJECTIVE: Obtaining an accurate weight is crucial during pediatric
      trauma/medical resuscitation. Currently, length-based weight estimations are
      used. Study objective was to assess feasibility of obtaining actual weights of
      children during trauma resuscitation and study its concordance with length-based
      estimated weight using the Broselow Pediatric Emergency Tape. METHODS: Pediatric
      trauma patients 0 to 14 years old presenting to a tertiary care pediatric trauma
      center between November 2008 and October 2009 were enrolled prospectively. Length
      based weight estimation was done on patient arrival using the Broselow tape; in
      addition, an actual patient weight was recorded using the trauma stretcher
      integrated weighing scale. RESULTS: Two hundred thirty-one patients were eligible
      and enrolled. Weights were recorded in 145 children (63.2%). In 27 patients
      (18.6%) whose body length exceeded Broselow tape range, weight was measured using
      stretcher scale only. The remaining 118 patients (mean age, 5.0 [SE +/- 0.3]
      years; 67% male) were used for correlation analysis. There was good correlation
      (Pearson correlation coefficient, r = 0.86) between estimated weight and measured
      weight. However, Bland-Altman analysis showed mean bias +2.6 kg (95% confidence
      interval [CI], 1.6-3.6 kg); lower/upper limits of agreement were -8.3 kg (CI, 
      10.0 to -6.6 kg) and 13.5 kg (CI, 11.7-15.2 kg). CONCLUSIONS: It is possible to
      obtain an actual patient weight during pediatric trauma resuscitation. Length
      based estimated weight using Broselow tape underestimated weight by 2.6 kg; the
      mean error was greatest in the highest weight category.

PMID- 22653454
TI  - "ABC-SBAR" training improves simulated critical patient hand-off by pediatric
      interns.
AB  - OBJECTIVES: This study was done to assess whether a modified "ABC-SBAR" mnemonic
      (airway, breathing, circulation followed by situation, background, assessment,
      and recommendation) improves hand-offs by pediatric interns in a simulated
      critical patient scenario. METHODS: Each of 26 interns reviewed a scenario
      involving a decompensating pediatric patient and gave a simulated hand-off to a
      responder. They received a didactic session on ABC-SBAR, then performed a second
      hand-off using another scenario. Two blinded reviewers assessed 52 video-recorded
      hand-offs for inclusion, order, and elapsed time to essential hand-off
      information using a scoring tool. RESULTS: Mean score of hand-offs increased
      after ABC-SBAR training (preintervention: 3.1/10 vs postintervention: 7.8/10, P <
      0.001). In hand-offs after ABC-SBAR training, the reason for the emergency call
      was more often prioritized before background information (preintervention: 4% vs
      postintervention: 81%, P < 0.001) and stated earlier (elapsed time
      preintervention: 19 seconds vs postintervention: 7 seconds, P < 0.001). Hand-offs
      including an airway or breathing assessment increased after training
      (preintervention: 35% vs postintervention: 85%, P = 0.001), and this information
      was also stated earlier (preintervention: 25 seconds vs postintervention: 5
      seconds, P < 0.001). Total hand-off duration was increased (preintervention: 29
      seconds vs postintervention: 36 seconds, P = 0.004). CONCLUSIONS: Unstructured
      hand-off by interns in a simulated patient emergency emphasizes background
      information, leaving essential information (such as reason for the call and ABCs)
      delayed or omitted. ABC-SBAR was associated with improved inclusion and
      timeliness of essential information in simulated critical patient hand-offs by
      pediatric interns; however, hand-off duration was increased. Further studies are
      needed to elucidate optimal hand-off in an emergency situation.

PMID- 22653455
TI  - Visceral leishmaniasis: a common cause of post-infectious febrile pancytopenia in
      children in an endemic area: experience of a children's tertiary hospital.
AB  - BACKGROUND: Visceral leishmaniasis (VL, kala-azar) is caused by Leishmania spp, a
      parasite that is commonly encountered in Mediterranean countries. Leishmaniasis
      usually presents with fever, hepatosplenomegaly, lymphadenopathy, and
      pancytopenia. OBJECTIVES: The aim of the study was to prospectively examine the
      characteristics of cytopenia associated with VL and compare it with other post
      infectious cytopenias observed in children with febrile illnesses. METHODS: We
      studied 112 children, aged (mean) 4.0 (SD, 3.8) years (range, 0-14 years), who
      were admitted to the pediatric ward because of febrile cytopenia associated with
      infections, during a 2-year period (March 2005 to June 2007). Study participants
      were investigated with measurement of acute-phase reactants, bacterial cultures,
      and serologic tests. RESULTS: Pancytopenia was detected in 9 (8%) of 112 patients
      (5 boys), with a mean age of 4.5 (SD, 3.0) years.The mean value of white blood
      cell was 3827 (SD, 1455)/mL; absolute neutrophil count, 1229 (SD, 655)/mL;
      hemoglobin, 8.3 (SD, 1.1) g/dL; and platelet count, 88,200 (SD, 20,186)/mL. All
      patients with pancytopenia had fever (mean duration, 8.9 [SD, 8.7] days) (maximum
      temperature, 39.5 degrees C [SD, 0.6 degrees C]) and hepatosplenomegaly (9/9),
      whereas 2 of 9 had lymphadenopathy. In these patients, a bone marrow aspiration
      was performed, and VL was detected in all 9 samples. They were treated with
      liposomal amphotericin B and had an excellent response rate. Pancytopenia
      resolved within a mean period of 17.6 (SD, 17.3) days (range, 8-60 days), and
      there was no relapse during a 2 years' follow-up. CONCLUSIONS: In endemic
      countries, leishmaniasis is the main cause of febrile pancytopenia among children
      in whom hematologic malignancy has been ruled out.

PMID- 22653456
TI  - Clinical and analytical characteristics and short-term evolution of enteroviral
      meningitis in young infants presenting with fever without source.
AB  - OBJECTIVE: The objective of this study was to describe the characteristics of the
      enteroviral meningitis diagnosed in a pediatric emergency department among
      infants younger than 3 months with fever without source and its short-term
      evolution. METHODS: This was a retrospective, cross-sectional, 6-year descriptive
      study including all infants younger than 3 months who presented with fever
      without source and who were diagnosed with enteroviral meningitis. RESULTS: A
      lumbar puncture was practiced at their first emergency visit in 398 (29.5%) of
      1348 infants, and 65 (4.8%) were diagnosed with enteroviral meningitis, 33 of
      them (50.7%) between May and July. Among these 65 infants, 61 were classified as
      well-appearing; parents referred irritability in 16 (25.3%) of them (without
      statistical significance when compared with infants without meningitis). Forty
      one (63.0%) had no altered infectious parameters (white blood cell [WBC] count
      between 5000 and 15,000/MUL, absolute neutrophil count less than 10,000/MUL, and
      C-reactive protein less than 20 g/L), and 39 (60%) had no pleocytosis. All of the
      65 infants recovered well, and none of them developed short-term complications.
      CONCLUSIONS: The symptoms in infants younger than 3 months with enteroviral
      meningitis were similar to those in infants with a self-limited febrile process
      without intracranial infection. C-reactive protein and WBC count were not good
      enteroviral meningitis predictors. Cerebrospinal fluid WBC count was normal in
      many of these infants, so performing a viral test is recommended for febrile
      infants younger than 3 months in which a lumbar puncture is practiced during warm
      months. The short-term evolution was benign.

PMID- 22653457
TI  - An intervention to improve pain management in the pediatric emergency department.
AB  - OBJECTIVE: The objective of this study was to measure the impact of a structured
      intervention on pain management in a pediatric emergency department (ED).
      METHODS: Data were prospectively collected from children presenting to an urban
      tertiary care pediatric ED before and after intervention. Data were collected on
      the rate and timeliness of analgesic administration, the assessment and
      reassessment of pain, periprocedural anesthesia, and patient satisfaction. The
      intervention was developed by a multidisciplinary committee composed of
      physicians, nurses, and child life specialists and was focused on correcting
      deficiencies identified before intervention data collection. It consisted of a
      policy defining pain, pain-appropriate analgesia, age-appropriate pain
      assessment, and adequate preprocedural and periprocedural analgesia.
      Implementation occurred through provider education, organizational changes, and
      patient empowerment. RESULTS: One hundred two patients were enrolled during the
      preintervention period, and 109 were enrolled in the postintervention period. The
      percentage of patients in pain receiving any analgesic increased from 34% to 50%,
      an increase of 16% (95% confidence interval [CI], 1%-30%). The median time to
      medication administration decreased from 97 minutes to 57 minutes, a decrease of
      40 minutes (95% CI, -84 to 4 minutes). The percentage of children receiving
      preprocedural analgesia increased from 10% to 62%, an increase of 52% (95% CI,
      12%-74%). Reassessment of pain by physicians increased from 6% to 76%, an
      increase of 70% (95% CI, 59%-78%). CONCLUSIONS: A structured intervention,
      tailored to pain management shortcomings commonly found in the pediatric ED, can
      lead to improvements in the treatment and prevention of pain in childhood
      emergencies.

PMID- 22653458
TI  - Factors associated with bowel resection among infants with intussusception in the
      United States.
AB  - BACKGROUND: Intussusception is the most common cause of infant bowel obstruction.
      Because delays in diagnosis can lead to severe outcomes, differentiating milder
      cases from those with potentially serious outcomes is important. OBJECTIVE: The
      objective of this study was to identify factors associated with bowel resection
      among intussusception cases using data from a large nationwide study, which
      investigated the association between intussusception and Rotashield. METHODS: We
      examined characteristics of 376 intussusception cases not associated with
      Rotashield use. Cases were confirmed by a radiologic procedure, surgery, or
      autopsy. Clinical characteristics of infants with and without bowel resection
      were compared. RESULTS: During the week before hospitalization, 93% of the 376
      infants with intussusception had vomiting, 72% reported bloody stool, 63% had
      hemoccult positive stool, 51% had diarrhea, 43% reported fever, and 14% had
      documented fever. Surgery was performed on 209 cases (56%). Of these 209 cases,
      33% (67/209) required bowel resection. Documented fever on admission
      significantly increased the risk of bowel resection (odds ratio, adjusted for
      race and sex, 2.7; 95% confidence interval, 1.2-6.0). Among infants with
      intussusception, the presence of a reported symptom for at least 2 days before
      hospital admission was also an independent predictor of bowel resection (adjusted
      odds ratio, 2.7; 95% confidence interval, 1.5-4.8). CONCLUSIONS: Bowel resection
      appears to be more likely among intussusception patients with documented fever
      and symptoms for at least 2 days. However, because resection also occurred among
      those without fever or prolonged symptoms, severe disease must also be considered
      in absence of these symptoms.

PMID- 22653459
TI  - Randomized trial comparing wound packing to no wound packing following incision
      and drainage of superficial skin abscesses in the pediatric emergency department.
AB  - OBJECTIVE: The objective of this study was to investigate the impact of wound
      packing versus no wound packing on short-term failure rates and long-term
      recurrences after incision and drainage (I&D) of a simple cutaneous abscess.
      METHODS: In this randomized, single-blind, prospective study, subjects between
      the ages 1 and 25 years with skin abscesses needing an I&D were enrolled
      consecutively and randomized to be packed or not packed following the procedure.
      Treatment failure was assessed at a 48-hour follow-up visit by a masked observer
      who rated the need for a major intervention (repeat I&D or re-exploration) or
      minor intervention (antibiotics initiated or changed, need for packing, or repeat
      visit). Pain scores were assessed using color analog scales before and after the
      procedure and repeated at the 48-hour follow-up visit. Healing and abscess
      recurrence were assessed via telephone interview at 1 week and 1 month. RESULTS:
      Fifty-seven subjects were enrolled over a 15-month period. Overall failure rates
      were similar between the groups, with 19 (70%) of 27 subjects in the packed group
      needing an intervention by 48 hours compared with 13 (59%) of 22 subjects in the
      nonpacked group who needed an intervention (difference, 11%; 95% confidence
      interval, -15% to 36%). Major and minor intervention rates were also similar.
      Pain scores did not significantly differ between groups. CONCLUSIONS: Wound
      packing does not appear to significantly impact the failure or recurrence rates
      after simple I&D. Larger studies are needed to better validate the equivalency of
      these 2 strategies.

PMID- 22653460
TI  - Effect of cough and cold medication withdrawal and warning on ingestions by young
      children reported to Texas poison centers.
AB  - OBJECTIVE: This study examined whether the withdrawal of over-the-counter cough
      and cold medication labeled for use in children younger than 2 years in October
      2007 and the warning against use of the products in children younger than 4 years
      in October 2008 affected cough and cold medication ingestions by young children
      reported to a statewide poison system. METHODS: Cases were all cough and cold
      medication ingestions by children aged 0 to 5 years reported to the Texas Poison
      Center Network during October 1998 to September 2009. The annual number of
      ingestions was determined, and the percent change from the previous year
      calculated. RESULTS: During October 1998 to September 2007, the number of
      ingestions exhibited a mean annual increase of 2.5%. The number of ingestions
      declined by 16.0% during October 2007 to September 2008 and 9.3% during October
      2008 to September 2009. During October 2007 to September 2008, the number
      decreased by 26.5% in children aged 0 to 1 years, 13.5% in those aged 2 to 3
      years, 5.4% in those aged 4 to 5 years, 23.4% therapeutic errors or adverse drug
      reactions, and 11.5% in all other circumstances. CONCLUSIONS: The voluntary
      withdrawal and subsequent voluntary warning of over-the-counter cough and cold
      medications appear to have resulted in a decline in ingestions reported to Texas
      poison centers not only among children aged 0 to 1 and 2 to 3 years but also
      among children aged 4 to 5 years, although the degree of decline was greatest for
      the youngest age groups. The decrease was observed not only among therapeutic
      errors and adverse drug reactions, but also in other circumstances of ingestion,
      although the decrease was greater for the former circumstances.

PMID- 22653461
TI  - Febrile seizures: current role of the laboratory investigation and source of the
      fever in the diagnostic approach.
AB  - OBJECTIVES: The aim of this study was to analyze the value of performing
      laboratory tests, taking cultures, and imaging, a diagnostic approach for febrile
      seizures (FSs) still routinely performed despite the American Academy of
      Pediatrics recommendations not to. Another aim of this study was to identify the
      most common sources of fever in patients with FSs and to determine whether the
      occurrence of FSs correlates with the seasons of the year. METHODS: This is a
      retrospective study that included all patients diagnosed with simple or complex
      FSs who were seen in the emergency room or inpatient unit from January 2004 to
      December 2009. RESULTS: Of the 219 patients included in the study, 135 (61.4%)
      cases had the etiology of the FS diagnosed. Upper respiratory tract infection,
      otitis media, urinary infection, and pneumonia were the most common diagnoses
      attributed to the fever. Leukocytosis was present in 48 (24%) of 219, and
      neutrophilia in 199 (91%) of 219 cases. Low bicarbonate levels were common among
      every age group. Only 1 blood culture was positive for Salmonella. The incidence
      of FS was higher during the winter (49.3% of the cases), and it closely
      paralleled the seasonal variation of viral infections. CONCLUSIONS: Even though
      laboratory tests, taking cultures, and imaging are performed in daily practice
      when approaching FSs, the association of FSs with serious infectious disease is
      rare and usually overestimated. The diagnostic approach should be individualized
      to each case and correlated with available data like that shown in this study.
      Parents should be educated with the knowledge that the occurrence of FSs tends to
      be higher in winter.

PMID- 22653462
TI  - Identification and validation of prognostic criteria for persistence of mild
      traumatic brain injury-related impairment in the pediatric patient.
AB  - OBJECTIVES: This study aimed to develop and validate prognostic criteria to
      identify children at risk for persistence of mild traumatic brain injury (MTBI)
      impairment. METHODS: A prospective cohort study was conducted among 11- to 17
      year-old emergency department (ED) patients admitted for MTBI. The Immediate
      Postconcussion Assessment and Cognitive Testing neurocognitive test was
      administered during hospitalization and at routine clinic follow-up (ImPACT).
      Logistic regression and receiver operating characteristic (ROC) analyses were
      used to develop prognostic criteria for MTBI-related impairment in 1 group and
      validate the criteria in a second group. Mild traumatic brain injury-related
      impairment was defined as any impairment (symptom score >8 or <25th percentile on
      at least 1 of 4 neurocognitive composite domains) or severe impairment (symptom
      score >12 or <25th percentile on at least 2 of 4 neurocognitive composite
      domains) present on follow-up. RESULTS: The derivation and validation cohorts
      were 42 and 21 patients (median age, 14 years; 71.4% male). Using the mean of the
      validation cohort patients' 4 neurocognitive deficit composite percentiles at
      baseline, a cut point of less than 39 percentile had high sensitivity (0.89) and
      specificity (0.80) and an area under the ROC curve of 0.85 in predicting the
      presence of any impairment at follow-up; it discriminated equally well in the
      validation cohort. A cut point of less than 27 percentile had good sensitivity
      (0.67) and specificity (0.67) and area under the ROC curve of 0.67 in predicting
      the presence of severe impairment in the derivation cohort at follow-up; it
      discriminated equally well in the validation cohort. CONCLUSIONS: This is the
      first study demonstrating prognostic criteria that may greatly help physicians
      identify patients who would benefit from structured follow-up care after MTBI.

PMID- 22653463
TI  - Petechiae/purpura in well-appearing infants.
AB  - BACKGROUND: Well infants with petechiae and/or purpura can present to emergency
      departments, and their management can be difficult. Many will have extensive
      investigations and treatment that may not be necessary. METHODS: This was a
      retrospective and descriptive audit investigating well infants (<8 months of age)
      presenting with petechiae or purpura in the absence of fever to a pediatric
      emergency department over a 91/2-year period. All presenting problems of
      petechiae or purpura were reviewed. Patients were excluded if they appeared
      unwell, were febrile or have a history of fever, or had eccyhmoses on
      presentation. RESULTS: Thirty-six babies were identified. The average age was 3.8
      months (range, 1-7 months). The majority of the infants had localized
      purpura/petechiae to the lower limbs (92%) with two thirds of these patients
      having bilateral signs. None had generalized signs. Most infants had a full blood
      count (94%), coagulation profile (59%) and C-reactive protein (59%), and blood
      cultures (59%), with all being normal (except for mild elevation in platelets).
      Nine patients were admitted for observation, with only 1 patient having
      progression of signs. This patient had a diagnosis of acute hemorrhagic edema of
      infancy. The rest of the patients were thought to have either a mechanical reason
      for their petechiae/purpura (tourniquet phenomena) or a formal diagnosis was not
      specified. CONCLUSIONS: Well infants with localized purpura and/or petechiae with
      an absence of fever are more likely to have a benign etiology. Further study is
      required to determine if a full blood count and coagulation profile is necessary,
      or a period of observation (4 hours) is all that is required. If there is no
      progression of signs, it is likely that they can be safely discharged. The likely
      cause may be due to a tourniquet phenomenon (eg, diaper).

PMID- 22653464
TI  - A presurvey and postsurvey of a web- and simulation-based course of ultrasound
      guided nerve blocks for pediatric emergency medicine.
AB  - OBJECTIVES: Fracture pain in the pediatric emergency department generally is
      treated with systemic analgesia using opioids. Fracture pain can alternatively be
      controlled with ultrasound (U/S)-guided nerve blocks for which only minimal
      training is available to pediatric emergency medicine physicians. This study
      evaluated the effects of a Web- and half-day simulation-based U/S course. Outcome
      measures were physician comfort level with and intention to use U/S-guided nerve
      blocks in clinical practice. METHODS: We conducted a presurvey and postsurvey
      study targeting pediatric emergency medicine physicians. Participants completed a
      Web-based tutorial and a half-day simulation program. Participants completed
      survey questionnaires to document their comfort level and intention to use U/S
      guided nerve blocks. Questionnaires were completed before, immediately after, and
      1 month after course. RESULTS: Eleven physicians participated in the study. The
      participants' comfort with and intention to use U/S-guided ulnar and femoral
      nerve blocks increased immediately after course, but neither increase was
      sustained 1 month after course. Immediately following the course, participants
      reported that the course addressed their learning needs (91%) and that they would
      consider advanced training (91%). One month after course, participants reported
      that they would partake in refresher courses (82%), particularly if offered once
      per year (64%). CONCLUSIONS: This study suggests that Web- and simulation-based
      learning can increase comfort and intention to use U/S-guided nerve blocks and
      the need for follow-on training. Participants reported that their learning needs
      were met but that they would need annual refresher courses.

PMID- 22653465
TI  - Capillary-channeled polymer (C-CP) fibers as a stationary phase for sample clean
      up of protein solutions for matrix-assisted laser/desorption ionization mass
      spectrometry.
AB  - Capillary-channeled polymer (C-CP) fibers are employed in a micropipette tip
      format to affect a stationary phase for the solid phase extraction (SPE) of
      proteins from buffer solutions prior to MALDI-MS analysis. Proteins readily
      adsorb to the polypropylene (PP) C-CP fibers while buffer species are easily
      washed off the tips using DI-H(2)O. Elution of the solutes is achieved with an
      aliquot of 50:50 ACN:H(2)O, which is compatible with the subsequent spotting on
      the MALDI target with the matrix solution. Lysozyme and cytochrome c are used as
      test species, with a primary buffer composition of 100 mM Tris-HCl. In this case,
      direct MALDI-MS produces no discernible protein signals. SPE on the C-CP fibers
      yields high fidelity mass spectra for 1 MUL sample volumes. Limits of detection
      for cytochrome c in 100 mM Tris-HCl are on the order of 40 nM. Extraction of
      cytochrome c from buffer concentrations of up to 1 M Tris-HCl, provides signal
      recoveries that are suppressed by only ~50% versus neat protein solutions.
      Finally, extraction of 3.1 MUM cytochrome c from a synthetic urine matrix
      exhibits excellent recovery.

PMID- 22653467
TI  - Intervertebral disc regeneration or repair with biomaterials and stem cell
      therapy--feasible or fiction?
AB  - The "gold standard" for treatment of intervertebral disc herniations and
      degenerated discs is still spinal fusion, corresponding to the saying "no disc -
      no pain". Mechanical prostheses, which are currently implanted, do only have
      medium outcome success and have relatively high re-operation rates. Here, we
      discuss some of the biological intervertebral disc replacement approaches, which
      can be subdivided into at least two classes in accordance to the two different
      tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). On the
      side of NP replacement hydrogels have been extensively tested in vitro and in
      vivo. However, these gels are usually a trade-off between cell biocompatibility
      and load-bearing capacity, hydrogels which fulfill both are still lacking. On the
      side of AF repair much less is known and the question of the anchoring of
      implants is still to be addressed. New hope for cell therapy comes from
      developmental biology investigations on the existence of intervertebral disc
      progenitor cells, which would be an ideal cell source for cell therapy. Also
      notochordal cells (remnants of the embryonic notochord) have been recently pushed
      back into focus since these cells have regenerative potential and can activate
      disc cells. Growth factor treatment and molecular therapies could be less
      problematic. The biological solutions for NP and AF replacement are still more
      fiction than fact. However, tissue engineering just scratched the tip of the
      iceberg, more satisfying solutions are yet to be added to the biomedical
      pipeline.

PMID- 22653466
TI  - Degree of ionization in MALDI of peptides: thermal explanation for the gas-phase
      ion formation.
AB  - Degree of ionization (DI) in matrix-assisted laser desorption ionization (MALDI)
      was measured for five peptides using alpha-cyano-4-hydroxycinnanmic acid (CHCA)
      as the matrix. DIs were low 10(-4) for peptides and 10(-7) for CHCA. Total number
      of ions (i.e., peptide plus matrix) was the same regardless of peptides and their
      concentration, setting the number of gas-phase ions generated from a pure matrix
      as the upper limit to that of peptide ions. Positively charged cluster ions were
      too weak to support the ion formation via such ions. The total number of gas
      phase ions generated by MALDI, and that from pure CHCA, was unaffected by the
      laser pulse energy, invalidating laser-induced ionization of matrix molecules as
      the mechanism for the primary ion formation. Instead, the excitation of matrix by
      laser is simply a way of supplying thermal energy to the sample. Accepting strong
      Coulomb attraction felt by cations in a solid sample, we propose three hypotheses
      for gas-phase peptide ion formation. In Hypothesis 1, they originate from the
      dielectrically screened peptide ions in the sample. In Hypothesis 2, the
      preformed peptide ions are released as part of neutral ion pairs, which generate
      gas-phase peptide ions via reaction with matrix-derived cations. In Hypothesis 3,
      neutral peptides released by ablation get protonated via reaction with matrix
      derived cations.

PMID- 22653469
TI  - In situ synthesis of nickel tiara-like clusters with two different thiolate
      bridges.
AB  - Four nickel clusters, cyclo-[{Ni(MU-S(i)Pr)(MU-SMe)}(6)] (1), cyclo-[{Ni(MU
      StBu)(MU-SMe)}(6)] (2), cyclo-[{Ni(MU-S(i)Pr)(MU-SEt)}(6)] (3) and cyclo-[{Ni(MU
      StBu)(MU-SEt)}(10)] (4), based on thiolate ligands have been successfully
      synthesized and characterized by elemental analysis, FT-IR spectra, UV-vis-NIR
      spectra, powder X-ray diffraction and single-crystal X-ray diffraction.
      Intriguingly, the SMe and SEt ligands are generated from solvothermal in situ
      ligand synthesis through the cleavage of the S-S bond respectively. The four
      nickel thiolate clusters exhibit tiara-like frameworks consisting of two
      different types of thiolate ligands.

PMID- 22653468
TI  - The possibility of using fibrin-based collagen as an antibiotic delivery system.
AB  - PURPOSE: Collagen and fibrin are known to have potential use as a local drug
      delivery system. This experimental study was designed to evaluate whether a
      fibrinogen-based collagen (FBC) fleece, coated with thrombin and aprotinin, can
      be used as an antibiotic delivery system. METHODS: In an in vitro study,
      gentamicin, fosfomycin, ampicillin, ciprofloxacin and dibekacin were absorbed by
      the FBC, Kirby-Bauer disks (KBDs), and expanded polytetrafluoroethylene. After
      washing with saline or phosphate buffer saline (PBS) 3 times for 6, 12 and 24 h,
      each sample was analyzed for antibiotic retention. In an in vivo study, we
      implanted the FBC onto mouse livers and dripped gentamicin and ciprofloxacin onto
      the FBC. The FBCs were subsequently collected and analyzed for their antibiotic
      activities. RESULTS: After irrigation with saline, each antibiotic showed
      different activities. After PBS washing, the FBC impregnated with each antibiotic
      had higher activity than the KBDs, and inhibited the bacterial growth by 60-80 %
      compared to the control. Gentamicin dripped onto the FBC could inhibit bacterial
      growth after 48 h in vivo without affecting the hemostatic properties of the FBC.
      However, the FBC treated with ciprofloxacin exhibited antibacterial activity for
      only 3 h. CONCLUSIONS: Some bases, including FBC, can retain antibacterial
      activities dependent on the ingredients of the base and the type of antibiotic.
      Gentamicin, but not ciprofloxacin, was retained in the FBC in vivo. These results
      suggest that absorbent FBC might be useful not only as hemostatic material, but
      also as a local drug-delivery system.

PMID- 22653470
TI  - Long conjugated 2-nitrobenzyl derivative caged anticancer prodrugs with visible
      light regulated release: preparation and functionalizations.
AB  - A series of anticancer prodrugs with different chemical functional groups were
      prepared, in which the styryl conjugated 2-nitrobenzyl derivatives were
      introduced as the phototrigger to regulate the drug (chlorambucil) release.
      Compared to the common 4,5-dimethoxy-2-nitrobenzyl caged compounds, most of the
      prodrugs exhibited large and redshifted one-photon absorption within the visible
      range. One-photon excitation for the drug release was studied by measuring UV-vis
      absorption, FT-IR, and HPLC spectra, which suggested that chlorambucil was
      released effectively and precisely by manipulating external light conditions. And
      the introduction of different functional groups made this type of prodrug a good
      platform to further react with some typical drug carriers and to further form
      excellent visible light responsive drug delivery systems. Moreover, the drug also
      could be effectively released under the excitation of two-photon at 800 nm with
      comparable photorelease efficiencies.

PMID- 22653479
TI  - Digital image analysis of diverse Mexican rice cultivars.
AB  - BACKGROUND: Digital image analysis has an important role in geographical
      provenance of grains, as it can provide parameters of size, shape and color,
      which are important quality parameters for the design of engineering processes
      such as drying and milling of grains. In this study, digital image analysis was
      used to classify nine rice cultivars based on different morphometric parameters
      using the three sides of the grain (lateral, ventral and axial), Feret diameter,
      and 10 different form factors and color parameters (CIE L*, a* and b*). RESULTS:
      Result of principal component analyisis was an equation with seven variables
      (area, perimeter, length, width, thickness, sphericity and color), which was
      useful for distinguishing between nine different cultivars. The morphometric and
      color parameters for the Mor A-98 and Mor A-92 varieties showed they had 88%
      similarity. The variability was expressed with a confidence of 95%. CONCLUSION:
      Multivariate analysis indicated that the lateral side is the most sensitive for
      the classification of Mexican rice grains because of its color and morphometric
      characteristics. These results showed the application of image analysis for the
      future classifications of grains.

PMID- 22653480
TI  - Face-infringement space: the frame of reference of the ventral intraparietal
      area.
AB  - Experimental studies have shown that responses of ventral intraparietal area
      (VIP) neurons specialize in head movements and the environment near the head. VIP
      neurons respond to visual, auditory, and tactile stimuli, smooth pursuit eye
      movements, and passive and active movements of the head. This study demonstrates
      mathematical structure on a higher organizational level created within VIP by the
      integration of a complete set of variables covering face-infringement. Rather
      than positing dynamics in an a priori defined coordinate system such as those of
      physical space, we assemble neuronal receptive fields to find out what space of
      variables VIP neurons together cover. Section 1 presents a view of neurons as
      multidimensional mathematical objects. Each VIP neuron occupies or is responsive
      to a region in a sensorimotor phase space, thus unifying variables relevant to
      the disparate sensory modalities and movements. Convergence on one neuron joins
      variables functionally, as space and time are joined in relativistic physics to
      form a unified spacetime. The space of position and motion together forms a
      neuronal phase space, bridging neurophysiology and the physics of face
      infringement. After a brief review of the experimental literature, the neuronal
      phase space natural to VIP is sequentially characterized, based on experimental
      data. Responses of neurons indicate variables that may serve as axes of neural
      reference frames, and neuronal responses have been so used in this study. The
      space of sensory and movement variables covered by VIP receptive fields joins
      visual and auditory space to body-bound sensory modalities: somatosensation and
      the inertial senses. This joining of allocentric and egocentric modalities is in
      keeping with the known relationship of the parietal lobe to the sense of self in
      space and to hemineglect, in both humans and monkeys. Following this inductive
      step, variables are formalized in terms of the mathematics of graph theory to
      deduce which combinations are complete as a multidimensional neural structure
      that provides the organism with a complete set of options regarding objects
      impacting the face, such as acceptance, pursuit, and avoidance. We consider four
      basic variable types: position and motion of the face and of an external object.
      Formalizing the four types of variables allows us to generalize to any sensory
      system and to determine the necessary and sufficient conditions for a neural
      center (for example, a cortical region) to provide a face-infringement space. We
      demonstrate that VIP includes at least one such face-infringement space.

PMID- 22653481
TI  - Reversible intracranial parenchymal changes in MRI after MCA aneurysm treatment
      with stent-assisted coiling technique; possible nickel allergy.

PMID- 22653482
TI  - The combined stress effects of atrazine and cadmium on the earthworm Eisenia
      fetida.
AB  - To assess the combined toxic effects of atrazine and cadmium on earthworms,
      specimens of Eisenia fetida were exposed in artificial soil to three
      concentrations of atrazine (0, 0.5, and 2.5 mg kg(-1)) and a range of
      concentrations of cadmium (Cd; 0, 0.03, 0.3, and 3.0 mg kg(-1)) both singly and
      as mixtures. The DNA damage and internal atrazine and cadmium concentrations were
      assessed in earthworms on days 7, 14, 21, and 28 of the treatment. The results
      showed that the olive tail moments (OTMs) at individual atrazine and cadmium
      concentrations were significantly higher than those of the controls (p < 0.01).
      As exposure to atrazine or cadmium progressed, the OTMs increased and the maximum
      value occurred on day 28. In all combined treatments, the OTMs were much less
      than those of the sum of individual atrazine and cadmium OTMs, suggesting that
      the combined effects of atrazine and cadmium were less than additive. The less
      than additive toxicity of atrazine and cadmium might be due to the formation of
      atrazine-cadmium complexes or the activation of detoxification isozymes.
      Moreover, there was a significant correlation between internal atrazine or
      cadmium concentrations and DNA damage in most exposures, indicating that body
      residues were consistent with toxicity response.

PMID- 22653483
TI  - Mama Grizzly and the polar bears.

PMID- 22653484
TI  - A balancing act: focus on aneuploidy.

PMID- 22653485
TI  - Perinatal exposures and Kawasaki disease in Washington State: a population-based,
      case-control study.
AB  - BACKGROUND: This study tested the hypothesis that selected perinatal exposures
      are associated with Kawasaki Disease (KD) in later childhood. METHODS: A
      retrospective, population-based, case-control study was performed. Children
      hospitalized for KD in Washington State from 1987 to 2007 (n = 995) were
      identified through hospital discharge records and were linked to birth
      certificates and birth hospitalization discharge records. Controls were randomly
      selected from remaining birth records. Maternal and infant exposure information
      was obtained from hospital discharge records. Unconditional logistic regression
      was used to obtain adjusted relative risk estimates and to explore the effect of
      gender on observed associations. RESULTS: After adjusting for race, gender and
      birth year, the following were significantly associated with KD: maternal age
      >=35 years (odds ratio [OR] 1.65; [95% confidence interval: 1.20-2.27]); mother
      of foreign birth (OR 1.36; [1.06-1.75]); maternal Group B streptococcal
      colonization (OR 0.51; [0.26-0.97]); and early infancy hospitalization (OR 1.42;
      [1.04-1.93]). Early hospitalization for bacterial illness was associated with a
      2.8-fold increased risk of KD (OR 2.84; [1.59-5.06]). There was weak evidence to
      suggest that the association between early hospitalization and KD varies by
      gender. CONCLUSIONS: This study provides preliminary evidence of association
      between certain perinatal exposures and KD and raises the possibility of late
      biological effects of immune exposures during infancy. The association between KD
      and early infectious exposures deserves further study.

PMID- 22653486
TI  - Variability in processes of care and outcomes among children hospitalized with
      community-acquired pneumonia.
AB  - BACKGROUND: Substantial care variation occurs in a number of pediatric diseases.
      METHODS: We evaluated the variability in healthcare resource utilization and its
      association with clinical outcomes among children, aged 1-18 years, hospitalized
      with community-acquired pneumonia (CAP). Each of 29 children's hospitals
      contributing data to the Pediatric Hospital Information System was ranked based
      on the proportion of CAP patients receiving each of 8 diagnostic tests. Primary
      outcome variable was length of stay (LOS), revisit to the emergency department or
      readmission within 14 days of discharge. RESULTS: Of 21,213 children hospitalized
      with nonsevere CAP, median age was 3 years (interquartile range: 1-6 years).
      Laboratory testing and antibiotic usage varied widely across hospitals;
      cephalosporins were the most commonly prescribed antibiotic. There were large
      differences in the processes of care by age categories. The median LOS was 2 days
      (interquartile range: 1-3 days) and differed across hospitals; 25% of hospitals
      had median LOS >= 3 days. Hospital-level variation occurred in 14-day emergency
      department visits and 14-day readmission, ranging from 0.9% to 4.9% and from 1.5%
      to 4.4%, respectively. Increased utilization of diagnostic testing was associated
      with longer hospital LOS (P = 0.036) but not with probability of 14-day
      readmission (Spearman rho = 0.234; P = 0.225). There was an inverse correlation
      between LOS and 14-day revisit to the emergency department (rho = -0.48; P =
      0.013). CONCLUSIONS: Wide variability occurred in diagnostic testing for children
      hospitalized with CAP. Increased diagnostic testing was associated with a longer
      LOS. Earlier hospital discharge did not correlate with increased 14-day
      readmission. The precise interaction of increased use with longer LOS remains
      unclear.

PMID- 22653487
TI  - Etiology and seasonality of viral respiratory infections in rural Honduran
      children.
AB  - BACKGROUND: Limited data are available in Honduras that describe the etiology and
      seasonality of respiratory infections, especially in rural outpatient settings.
      Better data may lead to improved therapeutic and preventive strategies. The goal
      of our study was to determine the viral etiology and seasonality of acute
      respiratory infections in a rural Honduran population of children. METHODS:
      Prospective clinic surveillance was conducted to identify children < 5 years of
      age presenting with respiratory symptoms of < 5 days duration. We obtained data
      on age, sex, medical history, breastfeeding history, symptoms, risk factors,
      household setting, temperature, respiratory rate and chest examination findings.
      To assess the association between specific viruses and weather, regional
      meteorological data were collected. Nasopharyngeal samples were tested for 16
      respiratory viruses using a multiplex polymerase chain reaction panel. RESULTS:
      From February 2010 through June 2011, 345 children < 5 years of age were
      enrolled; 17%, 23%, 30% and 31% were <6, 6-11, 12-23 and 24-60 months old,
      respectively. Including all clinics in the region, 44.5% of patients < 5 years of
      age with documented respiratory diagnoses were enrolled. At least 1 virus was
      identified in 75.4% children, of which 7.5% were coinfections; 13.3% were
      positive for parainfluenza, 11.9% for influenza, 8.1% for human metapneumovirus
      and 7.5% for respiratory syncytial virus. Rainfall correlated with parainfluenza
      (P < 0.0001), influenza (P < 0.0001), human metapneumovirus (P = 0.0182) and
      respiratory syncytial virus (P < 0.0001). CONCLUSIONS: These results suggest that
      the spectrum of viruses in ill, rural, Honduran children is similar to that in
      North and Central America, although the seasonality is typical of some tropical
      regions.

PMID- 22653488
TI  - Bacterial meningitis and pneumococcal serotype distribution in children in
      cameroon.
AB  - Acute bacterial meningitis causes a substantial number of deaths in Cameroon.
      Among 170 children with acute meningitis, 112 were positive for a bacterial
      pathogen when tested using polymerase chain reaction amplification, and
      Streptococcus pneumoniae accounted for 57.1% of cases. Pneumococcal serotype
      coverage by 13-valent pneumococcal conjugate vaccine was 62.1%. This study shows
      that in Cameroon, 13-valent pneumococcal conjugate vaccine coverage is less than
      what is estimated for other African countries.

PMID- 22653489
TI  - Infliximab treatment of pancreatitis complicating acute kawasaki disease.
AB  - Kawasaki disease can be associated with gastrointestinal complications, including
      pancreatitis. We describe a child in whom infliximab infusion for intravenous
      immunoglobulin-resistant Kawasaki disease coincided with marked clinical
      improvement of the patient's acute pancreatitis.

PMID- 22653490
TI  - Interferon gamma-induced protein-10 concentrations in children with previous
      tuberculosis infections and disease.
AB  - Interferon gamma-induced protein-10 is a diagnostic test for tuberculosis
      infection. There is no information on its concentrations over time. Interferon
      gamma-induced protein-10 was evaluated in 72 children formerly treated or in
      former contact with tuberculosis using Quantiferon Gold in-tube. Cases and
      contacts had similar interferon gamma-induced protein-10 concentrations.
      Concentrations varied with the tuberculin and interferon gamma release tests'
      concordance or discordance, and were independent of time.

PMID- 22653491
TI  - Priming mass spectrometry-based sulfoglycomic mapping for identification of
      terminal sulfated lacdiNAc glycotope.
AB  - In an effort to prime our mass spectrometry (MS)-based sulfoglycomic mapping
      platform technology for facile identification of sulfated lacdiNAc (GalNAcbeta1
      4GlcNAcbeta1-), we have re-examined the N-glycans of bovine thyroid stimulating
      hormone. We showed that MALDI-MS mapping of permethylated glycans in negative ion
      mode can give an accurate representation of the sulfated glycans and, through
      MS/MS, diagnostic ions can be derived that we can collectively define the
      presence of a terminal sulfated lacdiNAc moiety at high sensitivity. Based on
      these ions, which can also be produced by nanoESI-MS(n), we demonstrated that the
      glycome of an ovarian carcinoma cell line, RMG-1, comprises a high abundance of
      sulfated lacdiNAc epitopes carried on multiantennary complex type N-glycans
      alongside fucosylated, sialylated and/or sulfated lacNAc antennae. This
      represents the first report of a natural glycomic occurrence of sulfated lacdiNAc
      on a cell line, as opposed to other better-characterized presence on secreted
      glycoproteins from a handful of sources. It is anticipated that with improved
      methods of detection such as that developed in this work, we are likely to
      identify a wider occurrence of sulfated lacdiNAc and be able to more accurately
      delineate the regulatory mechanism dictating the choice of a cell type in
      synthesizing sulfated, sialylated, fucosylated and/or non-substituted lacdiNAc.

PMID- 22653492
TI  - An abnormal echo-bright structure seen in the ascending aorta: right coronary
      artery stent protrusion.

PMID- 22653493
TI  - [Direct antiviral treatment strategies in chronic hepatitis C].
AB  - The standard antiviral therapy for chronic hepatitis C is pegylated interferon
      alfa (PegIFN) and ribavirin since about 10 years. This treatment regimen leads to
      a sustained virological response (SVR) in 40-50 % of patients infected with HCV
      genotype 1 and in approx. 80 % of those infected with HCV genotype 2 or 3.  In
      recent years, many direct antiviral agents (DAA) have been developed and are
      being explored in clinical studies. These antiviral agents target different viral
      proteins that are central for HCV replication, incl. the NS3/4A protease, NS5B
      polymerase, and the NS5A protein. The protease inhibitors telaprevir and
      boceprevir have recently been approved for the treatment of chronic HCV genotype
      1 infection in combination with PegIFN and ribavirin. These triple therapies
      increase the SVR rates in HCV genotype 1 patients from 40-50 % to approx. 70 %.
      Other DAAs will likely be approved in the near future and may result in an IFN
      free antiviral therapy.

PMID- 22653494
TI  - A comparison of unilateral laminectomy with bilateral decompression and fusion
      surgery in the treatment of grade I lumbar degenerative spondylolisthesis.
AB  - BACKGROUND: Although unilateral laminectomy and bilateral decompression (ULBD) is
      effective in the treatment of degenerative spondylolisthesis (DSPL), few reports
      have compared the outcomes of ULBD and instrumented fusion for the treatment of
      DSPL. We describe here the clinical and radiological outcomes of ULBD and
      instrumented fusion surgery for the treatment of DSPL after a minimum 3-year
      follow-up. METHODS: We retrospectively analyzed the outcomes of 47 DSPL patients
      with radicular pain who underwent ULBD or instrumented fusion between January
      2005 and December 2007. Clinical outcomes were assessed using the numeric rating
      scale (NRS) for back and leg pain, the Oswestry Disability Index (ODI), and Short
      Form-36 Health Survey (SF-36). Radiological outcomes of ULBD were analyzed by
      determining changes in slippage, disc height translation, and angular difference
      on simple and dynamic X-rays. RESULTS: The mean NRS of back pain showed a
      significantly greater decrease in the fusion than the ULBD group, whereas the
      mean NRS of leg pain, mean ODI, and mean physical component summary and mental
      component summary of the SF-36 decreased similarly in the ULBD and fusion groups.
      Radiologically, the ULBD group showed a 2.1 +/- 3.10% change in mean slippage, a
      0.15 +/- 1.58 mm change in mean translation, a -0.91 +/- 4.48 degrees  change in
      mean angular difference, and a -1.83 +/- 1.69 mm change in mean disc height. In
      the ULBD group, three patients had residual pain and three had recurrent pain. In
      comparison, no patient in the fusion group reported residual pain, whereas five
      patients experienced recurrent radicular pain caused by adjacent segmental
      disease. CONCLUSIONS: Our findings suggest that ULBD is the recommendable
      procedure for the treatment of patients with grade I DSPL who have mainly
      radicular pain. Although the two groups showed similar clinical outcomes overall,
      radiological degeneration was not as serious after ULBD treatment. In our
      analysis, foraminal stenosis is a contraindication for ULBD in the treatment of
      grade I DSPL.

PMID- 22653495
TI  - Microsurgical anatomy of the dorsal thoracic rootlets and dorsal root entry
      zones.
AB  - BACKGROUND: For successful DREZ (dorsal root entry zone) surgery, optimal
      neuroanatomical orientation and precise microsurgical dissection are required.
      Although cervical, lumbar, and sacral spinal segments have been studied in
      detail, such information is not available for thoracic segments. The objective of
      this anatomical study is to comprehensively illustrate the microanatomical
      features of the thoracic DREZs and their variations. METHODS: Fifteen formalin
      fixed adult cadaveric spinal cords from T1 to T12 were used. The dorsal rootlet
      numbers, distance between the posteromedial and posterolateral sulcus, length of
      each DREZ, length of each segment, and mean length of the dorsal rootlets were
      measured under a surgical microscope. RESULTS: The longest DREZs were observed at
      the T6, T7, and T8 segments with mean values of 15.3 mm, 15.6 mm, and 15.4 mm,
      respectively. The longest segment was observed at the T10 segment with a mean
      value of 21.0 mm, and the shortest segment was observed at the T1 segment with a
      mean value of 13.5 mm. CONCLUSIONS: The highest dorsal rootlet density is at the
      T1 segment of the spinal cord, can be easily distinguished visually, and may be a
      useful surgical landmark. The DREZs in T6-7 segments are longest, while these two
      segments have the least number of rootlets. Because the dorsolateral tract is
      remarkably narrow and the dorsal horn is exceedingly deep, DREZ surgery at the
      thoracic level may be difficult and risky for the dorsal column and corticospinal
      tract. Acquaintance with the microanatomy of the DREZ in the thoracic spinal cord
      is crucial to DREZ surgery.

PMID- 22653496
TI  - Independent predictors for recurrence of chronic subdural hematoma.
AB  - BACKGROUND: Chronic subdural hematoma is characterized by blood in the subdural
      space that evokes an inflammatory reaction. Numerous factors potentially
      associated with recurrence of chronic subdural hematoma have been reported, but
      these factors have not been sufficiently investigated. In this study, we
      evaluated the independent risk factors of recurrence. METHODS: We analyzed data
      for 420 patients with chronic subdural hematoma treated by the standard surgical
      procedure for hematoma evacuation at our institution. RESULTS: Ninety-two (21.9
      %) patients experienced at least one recurrence of chronic subdural hematoma
      during the study period. We did not identify any significant differences between
      chronic subdural hematoma recurrence and current antiplatelet therapy. The
      recurrence rate was 7 % for the homogeneous type, 21 % for the laminar type, 38 %
      for the separated type, and 0 % for the trabecular type. The rate of recurrence
      was significantly lower in the homogeneous and trabecular type than in the
      laminar and separated type. We performed a multivariate logistic regression
      analysis and found that postoperative midline shifting (OR, 3.6; 95 % CI, 1.618
      7.885; p = 0.001), diabetes mellitus (OR, 2.2; 95 % CI, 1.196-3.856; p = 0.010),
      history of seizure (OR, 2.6; 95 % CI, 1.210-5.430; p = 0.014), width of hematoma
      (OR, 2.1; 95 % CI, 1.287-3.538; p = 0.003), and anticoagulant therapy (OR, 2.7;
      95 % CI, 1.424-6.960; p = 0.005) were independent risk factors for the recurrence
      of chronic subdural hematoma. CONCLUSIONS: We have shown that postoperative
      midline shifting (>=5 mm), diabetes mellitus, preoperative seizure, preoperative
      width of hematoma (>=20 mm), and anticoagulant therapy were independent
      predictors of the recurrence of chronic subdural hematoma. According to internal
      architecture of hematoma, the rate of recurrence was significantly lower in the
      homogeneous and the trabecular type than the laminar and separated type.

PMID- 22653498
TI  - Ferrocene species included within a pyrogallol[4]arene tube.

PMID- 22653497
TI  - Phosphosulindac (OXT-328) selectively targets breast cancer stem cells in vitro
      and in human breast cancer xenografts.
AB  - Pharmacological targeting of breast cancer stem cells (CSCs) is highly promising
      for the treatment of breast cancer, as the small population of CSCs appears
      responsible for tumor initiation and progression and also for resistance to
      conventional treatment. Here we report that the novel phosphosulindac (OXT-328,
      PS) selectively and effectively eliminates breast CSCs both in vitro and in vivo.
      PS reduced cell proliferation and induced apoptosis in various breast CSCs.
      Breast CSCs are resistant to conventional cancer drugs but are sensitive to PS.
      Long-term treatment of mixtures of cultured breast CSCs and breast cancer cells
      with PS preferentially eliminated the CSCs. PS impaired the ability of CSCs to
      form mammospheres and markedly suppressed the expression of CSC-related genes.
      More importantly, PS prevented by half (p = .06) the formation of tumors
      initiated by CSCs in immunodeficient mice, and inhibited by 83% (p < .05) the
      growth of already formed breast cancer xenografts, reducing the proportion of
      CSCs in them. PS suppressed the Wnt/beta-catenin pathway by stimulating the
      degradation of beta-catenin and its relocalization to the cell membrane and also
      blocked the epithelial-mesenchymal transition and the generation of breast CSCs.
      These results indicate that PS has a strong inhibitory effect against breast
      cancer, acting, at least in part, by targeting CSCs through a signaling mechanism
      involving Wnt signaling.

PMID- 22653499
TI  - Site-specific protein propargylation using tissue transglutaminase.
AB  - Transglutaminases (TGases) catalyse the transamidation of glutamine residues with
      primary amines. Herein we report the first FRET-based activity assay for the
      direct detection of the ligation (transamidation) reaction mediated by tissue
      TGase (TG2). This novel assay was then used in a microtiter plate-based screen of
      a library of 18 potential amine substrates. From this screen it was discovered
      that propargyl amine serves as an excellent substrate for TG2. Subsequently,
      propargyl amine and 2-azidoethyl amine were validated independently as TG2
      substrates with K(M) values of 44 +/- 4 MUM, and 0.99 +/- 0.06 mM, respectively.
      In a proof-of-principle protein labelling experiment, the protein casein was
      selectively functionalized with propargyl amine using TG2 and subsequently
      fluorescently labelled through a dipolar cycloaddition reaction with an azido
      fluorescein conjugate. This application demonstrates the strong potential of
      using TG2 for site-specific protein modification through a combination of
      enzymatic and bioorthogonal chemistry.

PMID- 22653512
TI  - Pain management after comprehensive stage 2 repair for hypoplastic left heart
      syndrome.
AB  - Achieving optimal pain control for children after complex cardiac surgery can be
      challenging. Recently, the hybrid approach to palliation of hypoplastic left
      heart syndrome (HLHS) was introduced as an alternative to the classic Norwood
      procedure. The second stage of the hybrid approach is a complex procedure known
      as comprehensive stage 2 (CS2). The authors have noted that pain control after
      the CS2 procedure is particularly difficult to manage. This report presents a
      review of the authors' pain management strategy in this clinical scenario and
      evaluates its efficacy. The medical records of patients who underwent CS2 repair
      of the hybrid procedure for HLHS between June 2008 and August 2011 were
      retrospectively reviewed. As a comparative group with a similar physiology,
      patients undergoing an isolated Glenn procedure also were reviewed. In addition
      to demographic data, the intraoperative use of narcotics and other adjunct
      medications for analgesia and sedation was recorded. Postoperatively, the mode of
      analgesia, the total opioid administered during the first 48 h postoperatively,
      and the nursing-assessed patient pain scores were recorded. Any adverse drug
      effect or need to adjust the analgesic regimen was recorded, as well as the
      timing of tracheal extubation. During the study period, 36 patients ranging in
      age from 4 to 14 months underwent the CS2 procedure, and 21 patients underwent a
      Glenn procedure. After CS2 repair, fentanyl was the opioid initially prescribed
      for all but 2 of the 21 patients managed with the nurse-controlled analgesia
      (NCA) delivery method and 15 patients managed with continuous infusion. After the
      Glenn shunt, all patients were prescribed NCA, with 20 patients receiving
      fentanyl and 1 patient receiving hydromorphone. The use of intraoperative
      dexmedetomidine caused a decrease in the total narcotic requirements, although
      this did not reach a statistical significance for either the extubated or
      intubated patients after CS2. The extubated patients who underwent the Glenn
      procedure received a smaller total equivalent dose of fentanyl during the first
      24 h (29.02 +/- 10.6 MUg/kg) than did the extubated patients after the CS2
      procedure, who received an average of 37.92 +/- 8.5 MUg/kg (P = 0.02). During the
      second 24 h, the extubated Glenn patients continued to receive less fentanyl, at
      an average dose of 7.02 +/- 11.5 MUg/kg compared with 27.7 +/- 23.1 MUg/kg for
      the CS2 patients (P = 0.02). The extubated patients who underwent the Glenn
      procedure required less NCA time (33.68 +/- 17.7) than the CS2 patients (57.9 +/-
      31.8 h) (P = 0.04). Dexmedetomidine use with the CS2 patients resulted in a trend
      toward lowering of the total fentanyl dose, but this did not reach statistical
      significance. The intubated patients who received dexmedetomidine after the CS2
      procedure had less NCA time (61.7 +/- 39.2 vs. 128.1 +/- 100 h; P = 0.02). After
      the CS2 procedure for palliation of HLHS, patients experience a complex pain
      profile that differs from the pain associated with the traditional Glenn
      procedure. This group of patients generally can be managed with fentanyl NCA.
      Achieving a balance between a proper level of analgesia and sedation in the
      setting of early tracheal extubation to optimize postoperative physiology can be
      challenging. The preliminary data suggest that improvements in pain management
      should be investigated given that more than 30 % of the pain scores in the CS2
      group were in the moderate to severe range compared with 18 % after the Glenn
      procedure.

PMID- 22653502
TI  - Mitochondrial function and malfunction in the pathophysiology of pancreatitis.
AB  - As a primary energy producer, mitochondria play a fundamental role in pancreatic
      exocrine physiology and pathology. The most frequent aetiology of acute
      pancreatitis is either gallstones or heavy alcohol consumption. Repeated episodes
      of acute pancreatitis can result in the development of chronic pancreatitis and
      increase the lifetime risk of pancreatic cancer 100-fold. Pancreatic cancer is
      one of the most common causes of cancer mortality with only about 3-4 % of
      patients surviving beyond 5 years. It has been shown that acute pancreatitis
      involves Ca2+ overload and overproduction of reactive oxygen species in
      pancreatic acinar cells. Both factors significantly affect mitochondria and lead
      to cell death. The pathogenesis of inflammation in acute and chronic pancreatitis
      is tightly linked to the induction of necrosis and apoptosis. There is currently
      no specific therapy for pancreatitis, but recent findings of an endogenous
      protective mechanism against Ca2+ overload--and particularly the potential to
      boost this protection--bring hope of new therapeutic approaches.

PMID- 22653513
TI  - Cerebral oximetry monitoring during preoperative phlebotomy to limit allogeneic
      blood use in patients undergoing cardiac surgery.
AB  - Preoperative phlebotomy can minimize the need for allogenic blood products.
      Frequently, removed blood is replaced with intravenous fluids to maintain
      euvolemia (acute normovolemic hemodilution [ANH]). During cardiopulmonary bypass
      (CPB), ANH may present problems when the circuit prime causes further
      hemodilution and unacceptably low hemoglobin. This investigation aimed to
      demonstrate that minimum volume replacement after preoperative phlebotomy can be
      used safely when guided by cerebral oxygenation (rSO(2)) measured by near
      infrared spectroscopy (NIRS). This prospective study included patients undergoing
      surgery for congenital heart disease. After preoperative phlebotomy, fluid
      replacement was guided by mean arterial pressure (MAP), heart rate, and rSO(2),
      which were measured at baseline, immediately after phlebotomy, and 15 and 30 min
      after phlebotomy. This study enrolled 38 patients ages 3 months to 50 years.
      Preoperative phlebotomy removed 9.3 +/- 2.9 mL/kg of blood, and 5.6 +/- 5.1 mL/kg
      of crystalloid was administered intraoperatively. Within 30 min after phlebotomy,
      23 patients had a MAP decrease of 20 % or more from baseline. This fall in MAP
      coincided with a decrease in rSO(2) of 20 or more at 2 of 114 measured points.
      Initially, rSO(2) decreased from 74 +/- 9 to 68 +/- 10 but thereafter remained
      constant. On five occasions, rSO(2) decreased 20 or more from baseline, but no
      patient's NIRS value was less than 45. A decrease in rSO(2) occurred more
      commonly in younger patients and those who had a larger volume of blood removed.
      Preoperative phlebotomy without significant volume replacement can be performed
      safely before CPB. Volume replacement may be more appropriately guided by rSO(2)
      than by hemodynamic variables.

PMID- 22653514
TI  - Subplasma membrane Ca2+ signals.
AB  - Ca(2+) may selectively activate various processes in part by the cell's ability
      to localize changes in the concentration of the ion to specific subcellular
      sites. Interestingly, these Ca(2+) signals begin most often at the plasma
      membrane space so that understanding subplasma membrane signals is central to an
      appreciation of local signaling. Several experimental procedures have been
      developed to study Ca(2+) signals near the plasma membrane, but probably the most
      prevalent involve the use of fluorescent Ca(2+) indicators and fall into two
      general approaches. In the first, the Ca(2+) indicators themselves are
      specifically targeted to the subplasma membrane space to measure Ca(2+) only
      there. Alternatively, the indicators are allowed to be dispersed throughout the
      cytoplasm, but the fluorescence emanating from the Ca(2+) signals at the
      subplasma membrane space is selectively measured using high resolution imaging
      procedures. Although the targeted indicators offer an immediate appeal because of
      selectivity and ease of use, their limited dynamic range and slow response to
      changes in Ca(2+) are a shortcoming. Use of targeted indicators is also largely
      restricted to cultured cells. High resolution imaging applied with rapidly
      responding small molecule Ca(2+) indicators can be used in all cells and offers
      significant improvements in dynamic range and speed of response of the indicator.
      The approach is technically difficult, however, and realistic calibration of
      signals is not possible. In this review, a brief overview of local subplasma
      membrane Ca(2+) signals and methods for their measurement is provided.

PMID- 22653516
TI  - Myotonia congenita with strabismus in a large family with a mutation in the SCN4A
      gene.
AB  - BACKGROUND/AIMS: To determine the genetic basis of myotonia congenita (MC) and
      strabismus in a large Caucasian family. METHODS: Seven patients making up four
      generations of a family with MC and strabismus were recruited. All patients had
      at least one standard ophthalmic examination, including best-corrected visual
      acuity, refraction, and ocular motility measurements. CLCN1 and SCN4A genes were
      sequenced and analysed for mutations. RESULTS: Five out of the seven family
      members were diagnosed with MC by clinical history and electromyography.
      Ophthalmic history and exam revealed eyelid myotonia and strabismus. All patients
      with MC were diagnosed with strabismus between the ages of 3 and 6 and required
      surgical restoration of ocular alignment. Sequencing results revealed a c.
      1333G>A; p. Val445Met mutation in the SCN4A gene. CONCLUSION: There are few
      reports describing eyelid myotonia and strabismus in patients diagnosed with MC.
      We found significant ocular involvement in a family with a mutation in SCN4A.
      Future studies may confirm that MC with significant ocular involvement can be
      used to direct genetic analysis.

PMID- 22653518
TI  - Post-traumatic endophthalmitis.

PMID- 22653515
TI  - Neuroimmunomodulation in unipolar depression: a focus on chronobiology and
      chronotherapeutics.
AB  - The rising burden of unipolar depression along with its often related sleep
      disturbances, as well as increasing rates of sleep restriction in modern society,
      make the search for an extended understanding of the aetiology and
      pathophysiology of depression necessary. Accumulating evidence suggests an
      important role for the immune system in mediating disrupted neurobiological and
      chronobiological processes in depression. This review aims to provide an overview
      of the neuroimmunomodulatory processes involved with depression and
      antidepressant treatments with a special focus on chronobiology,
      chronotherapeutics and the emerging field of immune-circadian bi-directional
      crosstalk. Increasing evidence suggests that chronobiological disruption can
      mediate immune changes in depression, and likewise, immune processes can mediate
      chronobiological disruption. This may suggest a bi-directional relationship in
      immune-circadian crosstalk. Furthermore, given the immunomodulatory effects of
      antidepressants and chronotherapeutics, as well as their associated beneficial
      effects on circadian disturbance, we--and others--suggest that these therapeutic
      agents may exert their chronobiotic effects partially via the neuroimmune system.
      Further research is required to better elucidate the mechanisms of immune
      involvement in the chronobiology of depression.

PMID- 22653517
TI  - Tomographic fundus features in pseudoxanthoma elasticum: comparison with
      neovascular age-related macular degeneration in Japanese patients.
AB  - PURPOSE: To determine the retinal and subretinal features characteristic to
      pseudoxanthoma elasticum (PXE) compared with age-related macular degeneration by
      using spectral-domain optical coherence tomography (SD-OCT) in Japanese patients.
      METHODS: We reviewed colour fundus photographs, fluorescein angiograms, and SD
      OCT images of 52 eyes (27 Japanese patients) with angioid streaks (AS) due to
      PXE. Then we compared the incidence of tomographic features between 24 eyes (24
      patient) with choroidal neovascularization (CNV) secondary to AS and 44 eyes (44
      patients) with CNV secondary to age-related macular degeneration (AMD). RESULTS:
      Secondary CNV was found in 44 eyes (84.6%) of 52 patients with PXE during follow
      up. We found characteristic round or ovoid tubular structures with highly
      reflective annular lines (termed 'outer retinal tubulation' (ORT)) in 31 (70.5%)
      of 44 eyes with CNV, but none were found in eyes without CNV. We also found
      characteristic undulations of Bruch's membrane in 38 (73.1%) eyes with AS. The
      incidence of ORT was significantly greater in eyes with CNV secondary to AS
      (70.8%; P=0.005) compared with eyes with CNV secondary to AMD (34.1%). The
      incidence of Bruch's membrane undulation was significantly greater in eyes with
      CNV secondary to AS (70.8%; P<0.0001) than in eyes with CNV secondary to AMD
      (11.4%). CONCLUSION: SD-OCT imaging clearly revealed a greater incidence of
      unique lesions, including ORT and Bruch's membrane undulation, in eyes in PXE
      patients with CNV secondary to AS than in eyes with CNV secondary to AMD.

PMID- 22653519
TI  - Relationship between perifoveal capillaries and pathomorphology in macular oedema
      associated with branch retinal vein occlusion.
AB  - PURPOSE: To study the relationship between macular ischaemia on fluorescein
      angiography (FA) and pathomorphology at the foveal centre delineated by spectral
      domain optical coherence tomography (OCT) in macular oedema (MO) associated with
      branch retinal vein occlusion (BRVO). METHODS: One hundred and five consecutive
      eyes of 105 patients with MO (centre point thickness (CPT) >= 300 MUm) associated
      with BRVO in which FA using Heidelberg Retinal Angiography 2 and Spectralis OCT
      were performed on the same day were retrospectively reviewed. We evaluated the
      foveal pathomorphology using OCT images and the association with macular
      ischaemia. RESULTS: Within 1 year from symptom onset, 94 eyes were classified
      with perfused macula (34 eyes) or non-perfused macula (60 eyes). Eyes with
      perfused macula had better visual acuity and less CPT than those with non
      perfused macula (P=0.024 and P<0.001, respectively). Fourteen eyes with perfused
      macula had serous retinal detachment (SRD) alone at the presumed foveal centre
      (SRD type); seven, a sponge-like swelling at that area (retinal swelling type);
      11, foveal cystoid spaces alone (cystoid MO (CMO) type), and 2, with both SRD and
      foveal cystoid spaces (SRD+CMO type). However, 58 eyes with non-perfused macula
      had foveal cystoid spaces (42 of CMO type and 16 of SRD+CMO type), with a
      significant association between them (P<0.001). Among 11 eyes with symptoms
      exceeding 1 year, 6 eyes had perfused macula, and none had the SRD type.
      CONCLUSION: Most eyes without foveal cystoid spaces have perfused macula in MO
      associated with BRVO.

PMID- 22653521
TI  - Longitudinal assessment of pain outcomes in the clinical setting: development of
      the "APOLO" electronic data capture system.
AB  - Data to fully evaluate the effectiveness of many commonly used interventions in
      the clinical pain management setting are inadequate. Clinical data collected for
      patient management often are not based on validated instruments, and this impedes
      the ability to conduct longitudinal research. To address these needs, modified
      patient intake and return visit forms were established and the Assessment of Pain
      Outcomes Longitudinal Electronic Data Capture system was developed. Data
      collection has been underway since November 22, 2010. As of December 7, 2011, 951
      New Patient and 688 Return Visit forms had been entered. The forms have been well
      received, with less than 6.5% failing to complete at least 90% of the data
      requested. Accuracy of data entry is excellent, with an error rate of 1 in 11,250
      potential data points. Data output converts easily to standard statistical
      programs. The creation of a pain outcomes database using validated measures and
      clinically relevant data is feasible.

PMID- 22653522
TI  - Resource planning for ambulance services in mass casualty incidents: a DES-based
      policy model.
AB  - Due to an increasing number of mass casualty incidents, which are generally
      complex and unique in nature, we suggest that decision makers consider operations
      research-based policy models to help prepare emergency staff for improved
      planning and scheduling at the emergency site. We thus develop a discrete-event
      simulation policy model, which is currently being applied by disaster-responsive
      ambulance services in Austria. By evaluating realistic scenarios, our policy
      model is shown to enhance the scheduling and outcomes at operative and online
      levels. The proposed scenarios range from small, simple, and urban to rather
      large, complex, remote mass casualty emergencies. Furthermore, the organization
      of an advanced medical post can be improved on a strategic level to increase
      rescue quality, including enhanced survival of injured victims. In particular, we
      consider a realistic mass casualty incident at a brewery relative to other
      exemplary disasters. Based on a variety of such situations, we derive general
      policy implications at both the macro (e.g., strategic rescue policy) and micro
      (e.g., operative and online scheduling strategies at the emergency site) levels.

PMID- 22653529
TI  - Structural requirements of research tissue banks derived from standardized
      project surveillance.
AB  - Tissue banks constitute decisive and rate-limiting resource and technology
      platforms for basic and translational biomedical research, notably in the area of
      cancer. Thus, it is essential to plan and structure tissue banking and allocate
      resources according to research needs, but essential requirements are still
      incompletely defined. The tissue bank of the National Center of Tumor Diseases
      Heidelberg (NCT) was founded with the intention to provide tissues of optimal
      quality and to prioritize the realization of research projects. We analysed its
      structure and prospective project management registration as well as tracking
      records for all projects of the NCT tissue bank as of its start in 2005 in order
      to obtain information that may be relevant for tissue bank planning. All project
      proposals submitted to the NCT tissue bank (n = 681) were included in the study.
      For a detailed evaluation of provided services, only projects that were completed
      until July 2011 (n = 605) were analysed. For these 605 projects, NCT tissue bank
      provided 769 specific services. In all projects/services, we recorded project
      leader, type and amount of material provided, type of research
      (basic/translational), work load of project and project completion. Furthermore,
      all completed projects were tracked after 90 days according to a standard
      protocol to determine principal investigators' (PI) satisfaction and quality of
      the provided material. Until July 2011, 605 projects had been successfully
      completed as documented by material transfer agreement. Of the projects, 72.7 %
      addressed basic research, 22.3 % were translational research projects and 3 %
      concerned epidemiological research; 91 % (n = 546) concerned a single PI and the
      NTC tissue bank. For these projects, 769 specific services were provided. Of
      these services, 288 concerned providing formalin-fixed and paraffin-embedded
      (FFPE) tissue (extracts, full size sections), 126 providing fresh frozen
      materials (including fresh frozen sections), 137 providing tissue micro-array
      (TMA)-based sections and 199 providing immunohistochemical services. Project
      tracking demonstrated that all projects had started within 90 days after
      reception of the material by the PIs, and PI satisfaction with provided material
      exceeded 97 %. Standardized registration and tracking provides valuable
      structural information for planning and financing of tissue banks and allocation
      of resources. The high number of completed projects as well as high user
      satisfaction demonstrates that structuring of tissue banks should be preferably
      research-oriented and highly efficient. The comparable number of requests for
      FFPE and fresh frozen tissue as well as TMA-based services underpins the need for
      a broad approach in terms of methods and material types in order to fulfil
      research needs.

PMID- 22653528
TI  - Neuroimaging studies of the aging HIV-1-infected brain.
AB  - Highly active antiretroviral therapy (HAART) has increased life expectancy among
      HIV-infected individuals, and by 2015, at least half of all HIV-infected
      individuals will be over 50 years of age. Neurodegenerative processes associated
      with aging may be facilitated by HIV-1 infection, resulting in premature brain
      aging. This review will highlight brain abnormalities in HIV patients in the
      setting of aging, focusing on recent neuroimaging studies of the structural,
      physiological, functional and neurochemical changes. Magnetic resonance imaging
      (MRI) and magnetic resonance spectroscopy studies performed during the pre-HAART
      era or on antiretroviral-naive subjects suggest an accelerated aging process,
      while those on HAART-treated subjects suggest premature brain atrophy. Diffusion
      tensor imaging studies yielded conflicting findings on the relationship between
      HIV and age in neuroasymptomatic individuals. Functional MRI studies found
      evidence of premature or accelerated aging processes in the brains of HIV
      subjects. Lastly, many age-related illnesses such as diabetes, stroke, and
      depression, as well as comorbid substance abuse, may further exacerbate the aging
      process in the HIV-infected brain, leading to premature or accelerated age
      related brain changes. Given the different pathologic or physiologic changes in
      the brain assessed by the different neuroimaging techniques, using a multimodal
      approach in longitudinal follow-up studies is recommended for future studies.

PMID- 22653532
TI  - [Remodeling in asthma, a comprehensive review].

PMID- 22653530
TI  - Impact of cell division on intracellular uptake and nuclear targeting with
      fluorescent SiC-based nanoparticles.
AB  - Semiconductor nanoparticles (NPs) became important and wide-used tool for cell
      imaging because of their unique remarkable properties. Nevertheless, all previous
      investigations in this area were done on proliferating cells. For the first time,
      this work demonstrates strong influence of cell active proliferation/contact
      inhibition of proliferation on uptake of NPs. In addition, we show that cell
      division plays key-role in penetration of silicon carbide based NPs (SiC NPs)
      inside the cell nucleus. This may very likely concern other types of NPs able to
      reach the cell nuclei. In particular, observed effect of cell division gives
      perspectives for future selective cancer treatment with NPs.

PMID- 22653533
TI  - [Therapy for small airways disease: basic principles and therapeutic
      implications].
AB  - This paper describes the possibility of targeting the small airways. In addition
      to aiding in the therapy for chronic obstructive lung diseases this may prove to
      be invaluable in the development of treatment strategies for diseases of the
      bronchioli. Essential factors in peripheral lung deposition include extra-fine
      particles, a slow and controlled inspiratory flow and an endexspiratory
      breathhold of 5 - 10 sec (especially for steroids). Due to methodological
      difficulties, clinical data comparing steroids with larger or extra-fine
      particles are limited in the field of asthma therapy. However, research suggests
      a trend for reduced symptoms, positively affected biomarkers and decreased lung
      hyperinflation when steroids with extra-fine particles are used.

PMID- 22653534
TI  - Utilizing ultrasonography in the diagnosis of pediatric fibroepithelial polyps
      causing ureteropelvic junction obstruction.
AB  - BACKGROUND: Fibroepithelial polyps are a rare cause of ureteropelvic junction
      (UPJ) obstruction in children. Preoperative US diagnosis of fibroepithelial
      polyps is infrequently reported, with intravenous pylogram and retrograde
      pyelography being most commonly used for diagnosis. OBJECTIVE: To recommend the
      most accurate process for diagnosing this disease in children by assessing a
      modified ultrasonographic procedure for the diagnosis of fibroepithelial polyps.
      MATERIALS AND METHODS: A retrospective review of US and IVP imaging studies
      performed in surgically and histologically confirmed cases of fibroepithelial
      polyps in children. Each child was asked to drink as much water as possible 30
      min before the US testing. For US, the renal pelvis, UPJ and the proximal ureter
      were inspected for an echogenic mass resulting in hydronephrosis. For IVP
      studies, abdominal plain films were performed at 7, 15 and 30 min following
      contrast injection. RESULTS: Thirty-five children, 34 boys and 1 girl, had
      confirmed fibroepithelial polyps. The children ranged in age from 3 to 14 years
      (mean age 9 years). Clinical presentation included intermittent vague abdominal
      pain (100%) and/or hematuria (9.7%) for a period ranging from 1 month to 5 years.
      Of the 35 children (37 polyps), 21 (23 polyps) were correctly diagnosed
      preoperatively with US, establishing a 62.2% (23/37) US accuracy rate. Twenty
      polyps were seen on the left, three on the right and two children had bilateral
      polyps. The masses were all mildly echogenic with defined edges. Eight children
      (9 polyps) had an IVP consistent with fibroepithelial polyps giving IVP an
      accuracy rate of 24.3% (9/37). CONCLUSION: US is an effective screening tool for
      identifying fibroepithelial polyps causing UPJ obstruction in children.

PMID- 22653536
TI  - Prenatal healthcare providers' Gaucher disease carrier screening practices.
AB  - PURPOSE: Gaucher disease carrier screening is controversial in the medical
      community. The goal of this study was to explore current Gaucher disease carrier
      screening practices of prenatal healthcare providers. METHODS: Prenatal
      healthcare providers were invited by email to complete an electronic-based
      survey. RESULTS: A total of 1,454 prenatal healthcare providers, including 209
      genetic counselors, 450 midwives, and 795 physicians, completed the study. The
      majority of genetic counselors (n = 208/209, >99%), physicians (n = 415/450,
      92%), and midwives (n = 634/795, 80%) currently offer Jewish ancestry disease
      carrier screening to couples in whom one or both partners are Jewish. Of
      providers who offer Jewish ancestry disease screening, the majority of genetic
      counselors (n = 199/208, 96%) and physicians (n = 352/415, 85%) always or
      sometimes offer Gaucher disease screening whereas the majority of midwives (n =
      357/634, 56%) never offer Gaucher disease screening. CONCLUSION: This study
      presents the first report of Gaucher disease carrier screening practices of the
      prenatal healthcare providers in North America. Our results indicate that Gaucher
      disease carrier screening is being offered at a high rate within the scope of
      Jewish ancestry-based carrier screening. This may highlight a need to move away
      from the debate as to whether Gaucher disease carrier screening should be offered
      and, instead, focus on how best to provide Gaucher disease carrier screening
      services.

PMID- 22653535
TI  - Tetrasomy 15q26: a distinct syndrome or Shprintzen-Goldberg syndrome phenocopy?
AB  - PURPOSE: The aim of this study was to characterize the clinical phenotype of
      patients with tetrasomy of the distal 15q chromosome in the form of a neocentric
      marker chromosome and to evaluate whether the phenotype represents a new clinical
      syndrome or is a phenocopy of Shprintzen-Goldberg syndrome. METHODS: We carried
      out comprehensive clinical evaluation of four patients who were identified with a
      supernumerary marker chromosome. The marker chromosome was characterized by G
      banding, fluorescence in situ hybridization, single nucleotide polymorphism
      oligonucleotide microarray analysis, and immunofluorescence with antibodies to
      centromere protein C. RESULTS: The marker chromosomes were categorized as being
      neocentric with all showing tetrasomy for regions distal to 15q25 and the common
      region of overlap being 15q26->qter. CONCLUSION: Tetrasomy of 15q26 likely
      results in a distinct syndrome as the patients with tetrasomy 15q26 share a
      strikingly more consistent phenotype than do the patients with Shprintzen
      Goldberg syndrome, who show remarkable clinical variation.

PMID- 22653538
TI  - Species typing of Cuban Trichomonas vaginalis virus by RT-PCR, and association of
      TVV-2 with high parasite adhesion levels and high pathogenicity in patients.
AB  - The viral infection of the parasite with T. vaginalis virus (TVV) may have
      important implications for trichomonal virulence. In this study we identified the
      TVV species isolated from Cuban T. vaginalis, using specie specific Reverse
      Transcriptase-PCR. Of the 37 clinical isolates studied, 21 were infected with
      TVV, 6 contained TVV-1, 12, TVV- 2 and 3 were co-infected with TVV-1 and -2. The
      strains infected with TVV showing highest adhesion level in comparison to not
      infected strains, with high statistical significance. The strains infected only
      with TVV-2 showing highest adhesion level in comparison to strains infected with
      TVV-1, with high statistical significance. The parasites classified as mild
      symptomatic are infected only with TVV-1, however the severe only with TVV-2.
      According to our results, it seems that only two TVV species are infecting the
      Cuban isolates. Further studies using higher number of strains should be
      conducted in order to corroborate these results.

PMID- 22653537
TI  - Frequency and characterization of porcine hokovirus (PHoV) in domestic pigs in
      eastern China.
AB  - This study reports the frequency and age distribution of porcine hokovirus (PHoV)
      in domestic pigs and characterizes the strains prevalent in eastern China. A
      total of 242 tissues from domestic pigs were tested for PHoV using PCR, and six
      near-full-length genome sequences were used for phylogenetic analysis. The PHoV
      sequences from domestic pigs in China showed a close relationship to sequences of
      isolates from Romania and Hong Kong. The results provide evidence that there are
      differences between PHoV in China compared to early isolates. PHoV infections are
      more frequent in 0- to 6-week-old pigs than in older ones.

PMID- 22653541
TI  - A new adjustable macular buckle designed for highly myopic eyes.

PMID- 22653542
TI  - Time course of silicone oil emulsification.
AB  - PURPOSE: To investigate the natural course of silicone oil emulsification after
      silicone oil tamponade usage in retinal detachment surgery. The presence of a
      group of patients whose silicone oil tamponades we preferred to keep as long as
      possible because of high risk of redetachment enabled us to investigate the
      course of in vivo silicone oil emulsification. METHODS: Thirty-two cases that
      were considered to have a high risk of redetachment after silicone oil removal
      were closely monitored, and it was preferred to keep the silicon oil as long as
      possible until first signs of silicone oil emulsification were observed. Any
      ocular complication directly related to the silicone oil tamponade did not arise
      in any of these cases, and the only indication for silicone oil removal was the
      signs of emulsification. RESULTS: The silicone oil emulsification time ranges
      from 5 months to 24 months with a mean of 13.2 +/- 4.8 months. In most cases, it
      occurs within the first year. However, there are also 2 cases where
      emulsification is not observed until the 24th month. CONCLUSION: It could be
      possible to extend the silicone oil removal time up to 1 year to achieve a stable
      retinal status in cases with a high risk of redetachment.

PMID- 22653543
TI  - Role of hyperglycemia-mediated erythrocyte redox state alteration in the
      development of diabetic retinopathy.
AB  - PURPOSE: To evaluate erythrocyte redox state and its surrogates in patients with
      different stages of diabetic retinopathy and their association with cellular
      metabolic derangement developed in retinal microvascular cells. METHODS: Sixty
      type 2 diabetic patients with nonproliferative diabetic retinopathy (NPDR), 85
      patients with proliferative diabetic retinopathy (PDR), and 70 patients with
      diabetes but without retinopathy were considered as diabetic control (DC) for the
      study. In addition, 65 normal individuals without diabetes were enrolled as
      healthy control in this study. Erythrocyte oxidized nicotinamide adenine
      dinucleotide phosphate / reduced nicotinamide adenine dinucleotide phosphate
      (NADP / NADPH), oxidized nicotinamide adenine dinucleotide / reduced nicotinamide
      adenine dinucleotide (NAD / NADH) glutathione, plasma and vitreous lactate, and
      pyruvate levels were determined by enzymatic reaction-based spectrophotometric
      assay for the patients and individuals. RESULT: Erythrocyte NADP+ to NADPH ratio
      to NADPH ratio was found to be significantly higher among NPDR and PDR patients
      compared with DC subjects (P < 0.0001). Erythrocyte-reduced glutathione was
      significantly decreased in patients of NPDR (P = 0.0004) and patients of PDR (P =
      0.0157) compared to DC. Erythrocyte NAD to NADH ratio was also significantly
      decreased in patients of NPDR (P < 0.0001) and PDR (P < 0.0001) compared to DC
      subjects. Lactate to pyruvate ratio of plasma was elevated significantly in
      patients with NPDR compared with DC (P < 0.0001) and those having PDR (P =
      0.0046). In the vitreous fluid, the lactate to pyruvate ratios were found to be
      significantly lower in normal individuals without diabetes compared with patients
      having PDR (P < 0.0001). CONCLUSION: Hyperglycemia-mediated erythrocyte redox
      state alterations might be a potential risk factor for the development of NPDR in
      poorly controlled diabetic subjects.

PMID- 22653544
TI  - Removal of silicone oil: prognostic factors and incidence of retinal
      redetachment.
AB  - PURPOSE: To evaluate the incidence of retinal redetachment after the removal of
      silicone oil endotamponade for complicated retinal detachment and identify
      possible factors affecting outcome. METHODS: This is a retrospective review of
      173 patients who underwent pars plana vitrectomy with silicone oil tamponade for
      complex retinal detachment and subsequent removal of silicone oil (ROSO). The
      outcome factors studied included anatomical success, best-corrected visual acuity
      and intraocular pressure pre- and post-ROSO. RESULTS: Anatomical success was
      achieved in 167 of the 173 eyes (96.5%) after ROSO. The mean duration of silicone
      oil tamponade was 70 +/- 48 weeks (median, 56 weeks; mode, 48 weeks). The cause
      for primary retinal detachment was proliferative diabetic retinopathy in 36
      (20.8%) and proliferative vitreoretinopathy in 137 of 173 cases (79.2%). Best
      corrected visual acuity of greater than 20/100 was achieved in 83 cases (49.4%)
      at 3 months after ROSO. Levene's test for equality of variances was used to
      determine the association between previous unsuccessful retinal surgeries and
      redetachment (P = 0.523) and between duration of endotamponade and anatomical
      success (P = 0.451). CONCLUSION: The incidence of retinal redetachment after ROSO
      in our study was 3.46%. Aggressive removal of the vitreous base, performing
      retinotomies, ensuring complete silicone oil filling for adequate tamponade, and
      argon retinopexy can lead to low complication rates and improved outcomes.

PMID- 22653545
TI  - Macular sensitivity and morphology after intravitreal injection of triamcinolone
      acetonide for macular edema with branch retinal vein occlusion.
AB  - PURPOSE: To evaluate the changes of macular sensitivity, thickness, and total
      macular volume after intravitreal injection of triamcinolone acetonide to treat
      macular edema with branch retinal vein occlusion. METHODS: Seventeen eyes of 17
      patients with branch retinal vein occlusion with macular edema received
      intravitreal triamcinolone acetonide. Using capillary nonperfusion on fluorescein
      angiography, patients were classified into nonischemic or ischemic groups.
      Microperimetry was used to measure macular sensitivity within the central 4
      degrees , 10 degrees , and 20 degrees  fields. Macular thickness and macular
      volume within these fields were measured by optical coherence tomography.
      RESULTS: The mean macular thickness within the central 4 degrees , 10 degrees ,
      and 20 degrees  fields decreased significantly after intravitreal therapy (all Ps
      < 0.001) as did total macular volume (all Ps < 0.001). Visual acuity was
      significantly better at 3 and 6 months (P = 0.002) as was the mean macular
      sensitivity within the three fields (all Ps < 0.05). There were no significant
      differences in the trend profile of macular thickness and volume within the three
      fields between the ischemic and nonischemic groups. There were also no
      significant differences in the trend profile of visual acuity and macular
      sensitivity. CONCLUSION: Intravitreal triamcinolone acetonide may improve macular
      sensitivity and morphology in patients with ischemic and nonischemic branch
      retinal vein occlusion.

PMID- 22653546
TI  - In vitro and in vivo antifungal properties of cysteine proteinase inhibitor from
      green kiwifruit.
AB  - BACKGROUND: Higher plants possess several mechanisms of defense against plant
      pathogens. Proteins actively synthesized in response to those stresses are called
      defense-related proteins which, among others, include certain protease
      inhibitors. It is of particular relevance to investigate plant natural defense
      mechanisms for pathogen control which include cystatins-specific inhibitors of
      cysteine proteases. RESULTS: In this study, a cysteine proteinase inhibitor
      (CPI), 11 kDa in size, was purified from green kiwifruit to homogeneity. Immuno
      tissue print results indicated that CPI is most abundant in the outer layer of
      pericarp, near the peel, and the inner most part of the pulp-sites where it could
      act as a natural barrier against pathogens entering the fruit. The purified
      protein (15 umol L(-1)) showed antifungal activity against two phytopathogenic
      fungi (Alternaria radicina and Botrytis cinerea) by inhibiting fungal spore
      germination. In vivo, CPI (10 umol L(-1)) was able to prevent artificial
      infection of apple and carrot with spore suspension of B. cinerea and A.
      radicina, respectively. It also exerted activity on both intracellular and
      fermentation fluid proteinases. CONCLUSION: Identification and characterization
      of plant defense molecules is the first step towards creation of improved methods
      for pathogen control based on naturally occurring molecules.

PMID- 22653547
TI  - The subjective duration of audiovisual looming and receding stimuli.
AB  - Looming visual stimuli (log-increasing in proximal size over time) and auditory
      stimuli (of increasing sound intensity over time) have been shown to be perceived
      as longer than receding visual and auditory stimuli (i.e., looming stimuli
      reversed in time). Here, we investigated whether such asymmetry in subjective
      duration also occurs for audiovisual looming and receding stimuli, as well as for
      stationary stimuli (i.e., stimuli that do not change in size and/or intensity
      over time). Our results showed a great temporal asymmetry in audition but a null
      asymmetry in vision. In contrast, the asymmetry in audiovision was moderate,
      suggesting that multisensory percepts arise from the integration of unimodal
      percepts in a maximum-likelihood fashion.

PMID- 22653548
TI  - Non-aqueous synthesis of isotropic and anisotropic actinide oxide nanocrystals.

PMID- 22653549
TI  - Communication and social deficits in relatives of individuals with SLI and
      relatives of individuals with ASD.
AB  - We investigate two aspects of the autism triad, communication and social
      difficulties, in relatives of specific language impairment (SLI) probands (with
      and without additional autistic symptomatology) as compared to relatives of
      autism spectrum disorder (ASD) and Down's syndrome (DS) probands. Findings
      involving 726 first degree relatives of 85 SLI, 99 ASD and 36 DS probands
      revealed a higher rate of communication difficulties in relatives of both
      subgroups of SLI probands compared to ASD and DS relatives. Similar levels of
      social deficits were found in relatives of SLI + ASD and ASD probands. There was
      a higher than would be expected rate (4.3 %) of ASD, particularly in siblings of
      SLI + ASD probands. Communication and social deficits appear to breed true in SLI
      and ASD.

PMID- 22653550
TI  - Inflatable hollow obturator prostheses for patients undergoing an extensive
      maxillectomy: a case report.
AB  - The presence of a large palatal or maxillary defect after partial or total
      maxillectomy for tumor, trauma or congenital deformation poses a challenge to
      prosthodontists, particularly when the use of an implant cannot be considered.
      This case report described the use of an air valve in a hollow silicone obturator
      to manufacture an inflatable obturator that could be extended further into
      undercut area to retain itself. The inflatable obturator exhibited adequate
      retention, stability and border sealing, thereby improving the
      masticatory,pronunciation and swallowing functions of patients. It may be a
      suitable alternative treatment option to an implant-retained obturator.

PMID- 22653552
TI  - The role of Notch in the differentiation of CD4+ T helper cells.
AB  - CD4+ T helper cells are playing critical roles in host defense to pathogens and
      in the maintenance of immune homeostasis. Naive CD4+T cells, upon antigen
      specific recognition, receive signals to differentiate into distinct effector T
      helper cell subsets characterized by their pattern of cytokine production and
      specific immune functions. A tight balance between these different subsets
      ensures proper control of the immune response. There is increasing evidence
      revealing an important role for Notch signaling in the regulation of CD4+T helper
      cell differentiation or function in the periphery. However, the exact mechanisms
      involved remain unclear and appear contradictory. In this review, we summarize
      current knowledge and discuss recent advances in the field to reconcile different
      views on the role of Notch signaling in the differentiation of functional T
      helper subsets.

PMID- 22653553
TI  - The relationships between adult juvenile idiopathic arthritis and employment.
AB  - OBJECTIVE: The chronicity of juvenile idiopathic arthritis (JIA) into adulthood
      and attendant potential disability may adversely influence educational attainment
      and the ability to secure and maintain gainful employment. We undertook this
      study to investigate the effects of patient- and disease-specific factors on
      education and employment outcomes in a group of adult patients with JIA. METHODS:
      We performed a cross-sectional study of 103 consecutive adults attending a JIA
      continuity clinic, and patients who consented completed questionnaires relating
      to educational achievement, employment status, and functional disability (the
      Health Assessment Questionnaire disability index [HAQ DI]), and, for those who
      were employed, the rheumatoid arthritis Work Instability Scale. We used the
      structural equation modeling technique to study key patient and disease variables
      for employment in adults with JIA. RESULTS: The median age of patients was 24
      years (range 17-71 years) with median disease duration of 19 years (range 7-67
      years). Functional disability (the mean HAQ DI score) was significantly lower in
      patients who were employed (P = 0.03) and in those with oligoarticular JIA (t =
      2.29, P = 0.02). Educational achievement was not influenced by JIA subtype (F =
      1.18, P = 0.33). Educational achievement measured by General Certificate of
      Secondary Education (GCSE) grades had a positive effect on the type of job
      achieved in later life (F = 11.63, P = 0.001), with greater success leading to
      more professional or managerial posts. In the complex structural equation model,
      job stability was influenced positively by educational achievement measured by
      GCSE grades and negatively by the HAQ DI score (t = 10.94, P = 6.36 * 10(-16) ).
      CONCLUSION: Educational attainment is key to successful employability and is
      influenced by functional disability rather than by JIA subtype. These findings
      have implications for choice of occupation and delivery of career advice to aid
      decision making by young people with JIA.

PMID- 22653551
TI  - Validity assessment and determination of the cutoff value for the Index of
      Complexity, Outcome and Need among 12-13 year-olds in Southern Chinese.
AB  - To validate the use of the Index of Complexity, Outcome and Need (ICON) in
      assessing orthodontic treatment need among 12-13 year-olds in southern China, we
      determined the threshold value of ICON based on Chinese orthodontists' judgments.
      The samples consisted of 335 students in grade 7 from 16 randomly selected middle
      schools in Chengdu, China. Three associate professors provided ICON scores for
      each participant and the results were compared with the gold standard judgments
      from 25 experts on treatment needs. Based on the gold standard, 195 casts
      belonged to the treatment category, while the rest 140 belonged to the no
      treatment category. With the international cutoff point of 43, the sensitivity
      and specificity of the ICON score were 0.29 and 0.98.The best compromise between
      sensitivity and specificity in Chengdu, compared with the gold standard, was
      found at a cutoff point of 29, and the sensitivity and specificity were 0.88 and
      0.83. When used to evaluate the treatment need of 12-13 year-olds in southern
      China, the international ICON cutoff value did not correspond well with Chinese
      orthodontists' judgments; a lower cutoff value of 29 offered a greater
      sensitivity and specificity with respect to expert orthodontists' perception of
      treatment need.

PMID- 22653554
TI  - Changes in biogenic amines of silver carp (Hypophthalmichthys molitrix) fillets
      stored at different temperatures and their relation to total volatile base
      nitrogen, microbiological and sensory score.
AB  - BACKGROUND: Biogenic amines have received considerable attention owing to their
      undesirable effects in humans. There are few studies of changes in biogenic amine
      contents related to freshwater fish. Silver carp is an important freshwater fish
      species in China. This study aimed to investigate the changes in biogenic amines
      and their relation to total volatile base nitrogen (TVB-N), microbiological and
      sensory score of silver carp fillets stored at 0, 3 and 15  degrees C. RESULTS:
      The total biogenic amine contents of all silver carp fillets (regardless of
      storage time and temperature) ranged from 13.05 to 318.10 mg kg(-1). Putrescine
      and histamine were the main biogenic amines in silver carp fillets during
      storage. Cadaverine was only detected after 12 days at 3  degrees C and after 2
      days at 15  degrees C. Spermidine and spermine contents increased during the
      early storage period and then slightly decreased. CONCLUSION: Low temperature
      could control the quality of silver carp fillets by inhibiting the contents of
      biogenic amines. Putrescine showed significant correlation with TVB-N, total
      aerobic content, sensory score, tryptamine and phenylethylamine. Putrescine was a
      good quality marker of silver carp fillets in the cold chain.

PMID- 22653556
TI  - Igf-I regulates pheochromocytoma cell proliferation and survival in vitro and in
      vivo.
AB  - IGFs are involved in malignant transformation and growth of several tissues,
      including the adrenal medulla. The present study was designed to evaluate the
      impact of IGF-I on pheochromocytoma development. We used a murine
      pheochromocytoma (MPC) cell line (MPC4/30) and an animal model with a reduction
      of 75% in circulating IGF-I levels [liver-IGF-I-deficient (LID) mice] to perform
      studies in vitro and in vivo. We found that, in culture, IGF-I stimulation
      increases proliferation, migration, and anchorage-independent growth, whereas it
      inhibits apoptosis of MPC cells. When injected to control and to LID mice, MPC
      cells grow and form tumors with features of pheochromocytoma. Six weeks after
      cell inoculation, all control mice developed sc tumors. In contrast, in 73% of
      LID mice, tumor development was delayed to 7-12 wk, and the remaining 27% did not
      develop tumors up to 12 wk after inoculation. LID mice harboring MPC cells and
      treated with recombinant human IGF-I (LID+) developed tumors as controls. Tumors
      developed in control, LID, and LID+ mice had similar histology and were similarly
      positive for IGF-I receptor expression. The apoptotic index was higher in tumors
      from LID mice compared with those from control mice, whereas vascular density was
      decreased. In summary, our work demonstrates that IGF-I has a critical role in
      maintaining tumor phenotype and survival of already transformed pheochromocytoma
      cells and is required for the initial establishment of these tumors, providing
      encouragement to carry on research studies to address the IGF-I/IGF-I receptor
      system as a target of therapeutic strategies for pheochromocytoma treatment in
      the future.

PMID- 22653557
TI  - Macrophage mineralocorticoid receptor signaling plays a key role in aldosterone
      independent cardiac fibrosis.
AB  - Mineralocorticoid receptor (MR) activation promotes the development of cardiac
      fibrosis and heart failure. Clinical evidence demonstrates that MR antagonism is
      protective even when plasma aldosterone levels are not increased. We hypothesize
      that MR activation in macrophages drives the profibrotic phenotype in the heart
      even when aldosterone levels are not elevated. The aim of the present study was
      to establish the role of macrophage MR signaling in mediating cardiac tissue
      remodeling caused by nitric oxide (NO) deficiency, a mineralocorticoid
      independent insult. Male wild-type (MRflox/flox) and macrophage MR-knockout
      (MRflox/flox/LysMCre/+; mac-MRKO) mice were uninephrectomized, maintained on 0.9%
      NaCl drinking solution, with either vehicle (control) or the nitric oxide
      synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (L-NAME; 150 mg/kg/d)
      for 8 wk. NO deficiency increased systolic blood pressure at 4 wk in wild-type L
      NAME/salt-treated mice compared with all other groups. At 8 wk, systolic blood
      pressure was increased above control in both L-NAME/salt treated wild-type and
      mac-MRKO mice by approximately 28 mm Hg by L-NAME/salt. Recruitment of
      macrophages was increased 2- to 3-fold in both L-NAME/salt treated wild-type and
      mac-MRKO. Inducible NOS positive macrophage infiltration and TNFalpha mRNA
      expression was greater in wild-type L-NAME/salt-treated mice compared with mac
      MRKO, demonstrating that loss of MR reduces M1 phenotype. mRNA levels for markers
      of vascular inflammation and oxidative stress (NADPH oxidase 2, p22phox,
      intercellular adhesion molecule-1, G protein-coupled chemokine receptor 5) were
      similar in treated wild-type and mac-MRKO mice compared with control groups. In
      contrast, L-NAME/salt treatment increased interstitial collagen deposition in
      wild-type by about 33% but not in mac-MRKO mice. mRNA levels for connective
      tissue growth factor and collagen III were also increased above control treatment
      in wild-type (1.931 +/- 0.215 vs. 1 +/- 0.073) but not mac-MRKO mice (1.403 +/-
      0.150 vs. 1.286 +/- 0.255). These data demonstrate that macrophage MR are
      necessary for the translation of inflammation and oxidative stress into
      interstitial and perivascular fibrosis after NO deficiency, even when plasma
      aldosterone is not elevated.

PMID- 22653558
TI  - Chronic prednisolone treatment aggravates hyperglycemia in mice fed a high-fat
      diet but does not worsen dietary fat-induced insulin resistance.
AB  - Synthetic glucocorticoids such as prednisolone have potent antiinflammatory
      actions. Unfortunately, these drugs induce severe adverse effects in patients,
      many of which resemble features of the metabolic syndrome, such as insulin
      resistance. In this study, we investigated whether adverse effects of
      prednisolone on glucose homeostasis are aggravated in mice with compromised
      insulin sensitivity due to a high-fat diet by applying various methods to analyze
      changes in insulin sensitivity in mice. C57BL/6J mice were fed a high-fat diet
      for 6 wk and treated with either prednisolone (10 mg/kg . d) or vehicle for the
      last 7 d. Insulin sensitivity and blood glucose kinetics were analyzed with state
      of-the-art stable isotope procedures in different experimental conditions.
      Prednisolone treatment aggravated fasting hyperglycemia and hyperinsulinemia
      caused by high-fat feeding, resulting in a higher homeostatic assessment model of
      insulin resistance. In addition, prednisolone-treated high-fat diet-fed mice
      appeared less insulin sensitive by detailed analysis of basal glucose kinetics.
      Remarkably, using hyperinsulinemic-euglycemic or hyperglycemic clamp techniques,
      neither hepatic nor peripheral insulin resistance was worsened in the group that
      was treated with prednisolone. Yet analysis of hepatic glucose metabolism
      revealed that prednisolone did alter glycogen balance by reducing glycogen
      synthase flux under hyperinsulinemic as well as hyperglycemic conditions. In
      addition to elevated insulin levels, prednisolone-treated mice showed a major
      rise in plasma leptin and fibroblast growth factor 21 levels. Our data indicate
      that prednisolone-induced adverse effects on glucose metabolism in high-fat diet
      fed mice do not reflect impaired insulin sensitivity but may be caused by other
      changes in the hormonal regulatory network controlling glucose metabolism such as
      fibroblast growth factor 21 and leptin.

PMID- 22653559
TI  - Diagnosis of latex allergy: the importance of hev B 11.
AB  - We present the cases of 5 patients with a positive clinical history of cutaneous
      symptoms due to contact with latex products. A latex allergological assessment
      was made through skin prick tests (SPTs) both with commercial latex extracts and
      extemporaneous glove extracts, and serum-specific IgE to latex and glove-use
      tests. In addition, serum-specific IgE to recombinant allergens for Hevea
      brasiliensis was dosed. Molecular diagnostics in association with the glove-use
      test and, to a lesser extent, the SPTs with glove eluate are useful diagnostic
      tests to confirm the diagnosis of latex allergy in patients with mucocutaneous
      symptoms.

PMID- 22653560
TI  - Simulation-based learning versus problem-based learning in an acute care
      pharmacotherapy course.
AB  - INTRODUCTION: There is a lack of comparative data with simulation-based learning
      (SBL) and other types of learning. The objective of the study was to determine
      whether high-fidelity simulation is superior to problem-based learning (PBL) for
      training pharmacy students in an acute care elective. METHODS: Twenty-nine
      pharmacy students enrolled in the Acute Care Pharmacotherapy Simulation course
      over 2 years voluntarily participated in this randomized, crossover study.
      Students were randomized to group 1 or 2. The SBL group consisted of students in
      group 1 who had SBL during study week 1 and group 2 students who had SBL in week
      2. The PBL group consisted of students in group 1 who had PBL cases during study
      week 2 and group 2 students who had PBL cases in week 1. The topics covered were
      management of dysrhythmias (week 1) and heart failure (week 2). RESULTS: The SBL
      group significantly improved compared with the PBL on postquiz scores. The SBL
      group performed at least 15% better in the clinical assessment (P = 0.013).
      Students in the SBL group performed significantly better in their critical
      thinking skills for problem list, pharmacotherapy plan, and monitoring plan.
      CONCLUSIONS: Learning was enhanced with the use of SBL compared with PBL.

PMID- 22653561
TI  - Assessing the use of multiple sources in student essays.
AB  - The present study explored different approaches for automatically scoring student
      essays that were written on the basis of multiple texts. Specifically, these
      approaches were developed to classify whether or not important elements of the
      texts were present in the essays. The first was a simple pattern-matching
      approach called "multi-word" that allowed for flexible matching of words and
      phrases in the sentences. The second technique was latent semantic analysis
      (LSA), which was used to compare student sentences to original source sentences
      using its high-dimensional vector-based representation. Finally, the third was a
      machine-learning technique, support vector machines, which learned a
      classification scheme from the corpus. The results of the study suggested that
      the LSA-based system was superior for detecting the presence of explicit content
      from the texts, but the multi-word pattern-matching approach was better for
      detecting inferences outside or across texts. These results suggest that the best
      approach for analyzing essays of this nature should draw upon multiple natural
      language processing approaches.

PMID- 22653562
TI  - Heterogeneity in osteosarcoma cell lines and the biological effects of the
      chemical structure of 25-hydroxyvitamin D3 and 1 a,25 dihydroxyvitamin D3.

PMID- 22653563
TI  - Engaging basic scientists in translational research.

PMID- 22653564
TI  - DNA synthesis as a therapeutic target: the first 65 years.

PMID- 22653565
TI  - Vermeer and Leeuwenhoek, figments of the imagination?

PMID- 22653566
TI  - Retraction.

PMID- 22653567
TI  - Volatile mediated interactions between bacteria and fungi in the soil.
AB  - Soil is one of the major habitats of bacteria and fungi. In this arena their
      interactions are part of a communication network that keeps microhabitats in
      balance. Prominent mediator molecules of these inter- and intraorganismic
      relationships are inorganic and organic microbial volatile compounds (mVOCs). In
      this review the state of the art regarding the wealth of mVOC emission is
      presented. To date, ca. 300 bacteria and fungi were described as VOC producers
      and approximately 800 mVOCs were compiled in DOVE-MO (database of volatiles
      emitted by microorganisms). Furthermore, this paper summarizes morphological and
      phenotypical alterations and reactions that occur in the organisms due to the
      presence of mVOCs. These effects might provide clues for elucidating the
      biological and ecological significance of mVOC emissions and will help to unravel
      the entirety of belowground' volatile-wired' interactions.

PMID- 22653570
TI  - This special issue on Soil Chemical Ecology, the 7th in our series, follows
      previous ones on Allelopathy, 2000.

PMID- 22653569
TI  - Direct proof of ingested food regurgitation by Spodoptera littoralis caterpillars
      during feeding on Arabidopsis.
AB  - Oral secretions of herbivorous lepidopteran larvae contain a mixture of saliva
      and regurgitant from the insect gut. Different compounds from the oral secretions
      can be recognized by the host plants and, thus, represent elicitors that induce
      plant defenses against feeding herbivores. Exogenously applied oral secretions
      can initiate the biosynthesis of jasmonates, phytohormones involved in the
      regulation of plant defense. However, it is not known (a) whether or not non
      manipulated insects indeed release oral secretions including gut-derived
      compounds into a leaf wound during the natural feeding process, or (b) whether
      they adjust the release of gut components to the state of plant defense. We
      addressed these questions by using Arabidopsis thaliana as host plant and larvae
      of the generalist herbivorous insect Spodoptera littoralis. We investigated the
      conversion of the plant-derived jasmonate precursor, cis-12-oxophytodienoic acid
      (cis-OPDA), to iso-OPDA by the larvae. This enzymatic reaction is mediated by a
      specific glutathione-S-transferase in the insect gut, but not in the plant. Any
      presence of iso-OPDA in plant tissue, thus, indicated that gut content had been
      regurgitated into the plant wound. Our study demonstrates that the plant is the
      only source for the substrate cis-OPDA by using aos (allene oxide synthase)
      mutants that are unable to synthesize OPDA. The fact that iso-OPDA accumulated
      over time on feeding-damaged leaves shows that the feeding larvae are constantly
      regurgitating on leaves. Although the larvae provided the signaling compounds
      that were recognized by the plant and elicited defense reactions, the larval
      regurgitation behavior did not depend on whether they fed on a defensive wild
      type plant or on a non defensive coi1-16 plant. This suggests that S. littoralis
      larvae do not adjust regurgitation to the state of plant defense.

PMID- 22653571
TI  - False-positive results from colorectal cancer screening in Catalonia (Spain),
      2000-2010.
AB  - OBJECTIVE: To identify factors associated with a false-positive result in a
      population-based colorectal cancer (CRC) screening programme with the faecal
      occult blood test (FOBT) in Catalonia between 2000 and 2010. METHODS: The study
      population consisted of participants of the Catalan CRC screening programme with
      a positive FOBT who underwent a colonoscopy for diagnostic confirmation from 2000
      to 2010. A false-positive result was defined as having a positive test but
      detecting no high-risk adenoma or cancer in the follow-up colonoscopy.
      Multivariate logistic regression models were performed to identify
      sociodemographic and screening variables related to false-positive results.
      Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were estimated.
      RESULTS: Over the screening period, 1074 (1.7%) of the 63,332 screening tests had
      a positive result in the Catalan CRC screening programme. The false-positive
      proportion was 55.2% (n = 546). Women were more likely to have a positive FOBT in
      the absence of CRC neoplasia than men (adjusted OR = 2.91; 95% CI: 2.22-3.28).
      During the first prevalence round, the proportion of false-positive results was
      higher than in subsequent rounds (69.5% vs. 48.9%; P < 0.05). Re-screening and
      having a bleeding pathology such as haemorrhoids or anal fissures were also
      associated with a false-positive result. CONCLUSION: The proportion of false
      positive results and the associated risks should be estimated to provide an
      eligible population with more reliable information on the adverse effects of
      screening.

PMID- 22653568
TI  - Ant interactions with soil organisms and associated semiochemicals.
AB  - This review focuses on the semiochemical interactions between ants and their soil
      environment. Ants occupy virtually every ecological niche and have evolved
      mechanisms to not just cope with, but also manipulate soil organisms. The
      metapleural gland, specific to ants was thought to be the major source of
      semiochemical antimicrobial compounds targeting general or specific deleterious
      microbes. The extremely diverse variety of semiochemicals and their sources with
      antimicrobial activity or potential activity is highlighted. The leaf-cutting
      ants and fire ant provide the most researched species, in part because they cause
      significant economic damage. The leaf-cutting ant is particularly interesting
      because researchers have uncovered unexpected interactions between leaf-cutting
      ant fungal farm, parasitic fungi, bacteria, yeasts, and ant defensive
      semiochemicals. These complex relationships highlight the multidimensional
      aspects of ants and the soil environment in which they live.

PMID- 22653572
TI  - Recruitment methods employed in the National Lung Screening Trial.
AB  - OBJECTIVES: To report participant recruitment experiences in a large, US
      randomized controlled trial (RCT) of lung cancer screening, with the aim of
      providing information that may be of use to researchers who wish to conduct
      similar future studies. SETTING: The National Lung Screening Trial (NLST), an RCT
      that demonstrated a 20% lung cancer mortality reduction with low dose helical
      computed tomography screening, relative to single-view chest radiograph
      screening. Thirty-three US medical centres recruited 53,454 participants from
      August 2002 through April 2004. METHODS: After recruitment was completed, centre
      co-ordinators were asked to complete a questionnaire addressing the extent to
      which specific methods were used and, for each specific method, numbers enrolled
      and total cost of the effort. Cost per enrollee was calculated. Co-ordinators
      also were asked to report lessons learned. RESULTS: Twenty-two centres returned
      questionnaires. Use of recruitment method varied by centre. Among centres
      reporting number enrolled by method, about 19,000 participants were enrolled with
      direct mail, about 4200 with mass media, and about 1000 with community outreach.
      Cost per enrollee varied across centres but medians were (US) $101 (direct mail),
      $79 (mass media), and $4 (community outreach). Co-ordinators reported that it was
      important to know where to find persons likely to be eligible and interested, and
      how best to approach them. CONCLUSIONS: Most NLST participants were recruited
      through direct mail, although median cost per participant was highest for that
      method.

PMID- 22653574
TI  - First trimester, second trimester, and integrated screening for Down's syndrome
      in China.
AB  - OBJECTIVE: To compare the effectiveness of first trimester, second trimester, and
      integrated screening for Down's syndrome. SETTING: Two prenatal diagnosis centres
      in China. METHODS: A total of 11,966 pregnant women (>=18 years) were screened
      over 21 months. First trimester screening (11-13 weeks) comprised measurement of
      serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated
      protein-A concentrations, and fetal nuchal translucency thickness. Second
      trimester screening (15-20 weeks) comprised measurement of beta-hCG and alpha
      fetoprotein concentrations. Computer software was used to calculate the risk of
      carrying a Down's syndrome fetus. RESULTS: The overall incidence of Down's
      syndrome was 0.2% (23/11,966). When the false-positive rate was fixed at 5%,
      detection rates for first trimester, second trimester, and integrated screening
      were 73.9%, 69.6%, and 82.6%, respectively. When the false-positive rate was
      fixed at 3%, detection/sensitivity rates for first trimester, second trimester,
      and integrated screening were 65.2%, 56.5%, and 73.9%, respectively. CONCLUSIONS:
      These findings suggest that integrated screening was the most effective means of
      screening for Down's syndrome in a Chinese population.

PMID- 22653573
TI  - The impact of media coverage of the Flexible Sigmoidoscopy Trial on English
      colorectal screening uptake.
AB  - OBJECTIVE: To assess the impact of media coverage of the UK Flexible
      Sigmoidoscopy Trial on colorectal screening uptake in England. SETTING: In April
      2010, publication of the UK Flexible Sigmoidoscopy (FS) Trial results generated
      considerable media interest in both FS and colorectal cancer (CRC) generally.
      METHODS: We used routinely collected data from the south of England (excluding
      London) to analyse return of faecal occult blood test (FOBt) kits within 28 days
      of the invitation (early uptake) among 60-69 year olds, before (T1, n = 31,229),
      around the time of (T2, n = 39,571), and one month after (T3, n = 33,430) the FS
      publicity. RESULTS: FOBt uptake over the whole period was 58.2%, with 38.4% of
      the kits returned within 28 days (early uptake). Across the three time periods,
      early uptake was 35.8% at T1, 39.4% at T2, and 39.7% at T3. Multivariate
      regression controlling for age, gender and socioeconomic status confirmed that
      uptake was higher if people received the FOBt kit around the time of the media
      coverage (T2: odds ratio [OR] = 1.17, 95% CI = 1.13-1.20), or one month after
      (T3: OR = 1.18, 95% CI = 1.15-1.22) than before (T1). Sub-group analyses
      demonstrated that the impact was stronger among previous non-responders than
      among first-time invitees or previous responders (P < 0.001). CONCLUSION: Media
      coverage of the FS Trial appeared to have a small but positive impact on FOBt
      screening uptake, especially among people who had previously abstained from
      screening.

PMID- 22653575
TI  - The impact of Jade Goody's diagnosis and death on the NHS Cervical Screening
      Programme.
AB  - OBJECTIVES: In August 2008 the British reality TV star Jade Goody made public her
      diagnosis of cervical cancer. In February 2009 it was announced that she was
      terminally ill and she died a few weeks later. A surge in cervical screening
      attendances associated with these events was widely reported. This paper aims to
      quantify the size of that effect across England, its duration, and whether it
      affected some groups of women more than others. SETTING: The Cervical Screening
      Programme in England. METHODS: Routinely collected statistics for the months
      around Jade Goody's diagnosis and death were compared with those for other
      periods. RESULTS: About half a million extra cervical screening attendances
      occurred in England between mid-2008 and mid-2009, the period during which Jade
      Goody was diagnosed and died; among these were 370 attendances where the test
      result was suspected neoplasia. At its peak in March 2009, attendance was 70%
      higher than expected. Increases were seen in both initial and follow-up screening
      attendances and in colposcopy attendances, and at all ages, though the magnitude
      was greater for women aged under 50. A substantially greater proportion of the
      extra attendances of women aged 25-49 on routine recall occurred in women whose
      attendance was overdue (28% occurred at 60 months or more) and relatively little
      represented over-screening (8% had been screened within the last 30 months).
      CONCLUSIONS: The pattern of increased attendance mirrored the pattern of media
      coverage of Jade Goody's diagnosis and death. It is likely that the increased
      screening resulted in a number of lives saved.

PMID- 22653576
TI  - Pd-catalyzed cross-coupling of aryl carboxylic acids with propiophenones through
      a combination of decarboxylation and dehydrogenation.
AB  - A Heck of a reaction: With a PCy(3)-supported Pd catalyst, aryl carboxylic acids
      cross-couple to saturated propiophenones through a combination of decarboxylation
      and dehydrogenation to give chalcones bearing a variety of functional groups in
      generally good yields (see scheme). Furthermore, a one-pot procedure, involving
      this reaction and a subsequent selective hydrogenative cyclization process, has
      been developed for the facile synthesis of quinoline derivatives from 2
      nitrobenzoic acids.

PMID- 22653577
TI  - Microsporogenesis in Brachiaria  brizantha (Poaceae) as a selection tool for
      breeding.
AB  - The  genus Brachiaria comprises more than 100 species and is the single most 
      important genus of forage grass in the tropics. Brachiaria brizantha,  widely
      used in Brazilian pastures for beef and dairy production, is native to  tropical
      Africa. As a subsidy to the breeding program underway in Brazil,  cytological
      studies were employed to determine the chromosome number and to  evaluate
      microsporogenesis in 46 accessions of this species available at  Embrapa Beef
      Cattle (Brazil). Thirty-four accessions presented 2n = 36; seven  had 2n = 45,
      and five had 2n = 54 chromosomes. Based on the higher level of  chromosome
      association observed in diakinesis, in tetra-, penta-, and  hexavalents,
      respectively, it was concluded that they are derived from x = 9;  consequently,
      these accessions are tetra- (2n = 4x = 36), penta- (2n = 5x =  45), and
      hexaploids (2n = 6x = 54). The most common meiotic abnormalities were  irregular
      chromosome segregation due to polyploidy. Chromosome stickiness,  abnormal
      cytokinesis, non-congressed bivalents in metaphase I and chromosomes  in
      metaphase II, and chromosome elimination were recorded at varying  frequencies in
      several accessions. The mean percentage of meiotic abnormalities  ranged from
      0.36 to 95.76%. All the abnormalities had the potential to affect  pollen
      viability by generating unbalanced gametes. Among the accessions, only  the
      tetraploid ones with less than 40% of abnormalities are suitable as pollen 
      donors in intra- and interspecific crosses. Currently, accessions with a high 
      level of ploidy (5 and 6n) cannot be used as male genitors in crosses because  of
      the lack of sexual female genitors with the same levels of ploidy.

PMID- 22653578
TI  - Characterization of  microsatellite markers in cassava based on microsatellite
      AFLP technique.
AB  - We  developed molecular markers for cassava based on the microsatellite-amplified
      fragment length polymorphism (M-AFLP) technique. Twenty primer pairs were 
      developed and used for the analysis of 48 samples of Manihot species,  consisting
      of M. esculenta (33), M. esculenta ssp flabellifolia (3), M. chlorosticta (3), M.
      carthaginensis (3), M.  filamentosa (3), and M. tristis (3). Nine microsatellite
      loci that  were polymorphic among these Manihot species were identified, giving
      32  polymorphic alleles and from two to seven alleles per locus. Unbiased and 
      direct count heterozygosity varied from 0.0233 to 0.7924 and 0.0000 to 0.7083, 
      respectively. There was significant deviation (P < 0.05) from Hardy-Weinberg 
      equilibrium at five loci. Genotypic data from the Manihot species were  subjected
      to genetic diversity analysis. We found that M. chlorosticta and M. esculenta ssp
      flabellifolia were the closest populations,  while M. filamentosa and M.
      esculenta ssp flabellifolia were  the most divergent. Considering within M.
      esculenta, the samples from  Nigeria and Fiji were the most closely related,
      while those from Venezuela and  of unknown origin were the most divergent. We
      conclude that the M-AFLP  technique is an effective method for generating
      microsatellite markers that are  useful for genetic diversity analysis in Manihot
      species.

PMID- 22653579
TI  - Molecular cloning and single  nucleotide polymorphism analysis of IGF2a genes in
      the common carp (Cyprinus carpio).
AB  - We  studied whether two IGF2 transcripts in common carp are similar to those 
      found in zebrafish. The full-length IGF2a cDNA contains a 5'-terminal 
      untranslated region (UTR) of 105 bp, a 3'-terminal UTR of 1358 bp and an open 
      reading frame of 612 bp, which encodes a 206-amino acid protein. A 6614-bp  full
      length IGF2a DNA molecule, including the 5'-flanking region, was  isolated.
      Genomic DNA structure analysis revealed that the IGF2a gene  contains four exons
      and three introns. Bioinformatics analysis indicated that  the proteins encoded
      by IGF2a genes in common carp have one signal  peptide and one apparent
      transmembrane region. Bootstrapping was performed 1000  times to obtain support
      values for each branch. The common carp IGF2a were  clustered in one group, while
      the outgroup (common carp IGF1) clustered  in another group. We identified two
      new single nucleotide polymorphisms in  intron 2 of the gene. One polymorphism,
      A/N, can be found only in the Huanghe  carp. The other polymorphism, C/N, can be
      found in both male Huanghe carp *  female Heilongjiang carp and male Huanghe carp
      * female Jian carp. The second  polymorphism, C/N, is primarily transferred from
      the male and may be related to  heterosis.

PMID- 22653580
TI  - Identification and  characterization of a novel Iraqi isolate of Fusarium
      pseudograminearum causing  crown rot in wheat.
AB  - Crown  rot is one of the main important fungal diseases affecting wheat in many
      areas  of the world, including Australia, USA, and Iran. Until now, there had
      been no  report of this pathogen in Iraq. Plants displaying crown rot symptoms
      were  observed in Shaat Alarab (Basra, Iraq); we investigated the causal agent of
      the  disease. Samples were surface-sterilized in bleach (1% available chlorine)
      and  cultured on quarter-strength potato dextrose agar plates. DNA was extracted 
      from fungal mycelia, using a modified CTAB protocol. The ITS/5.8S regions were 
      amplified using primer pair ITS1 and ITS4. PCR products purified using a gel 
      extraction kit were sequenced. The sequence that was detected was used to BLAST 
      against NCBI data. The most similar sequence was the ITS/5.8S rDNA region of
      Fusarium  pseudograminearum (strain NRRL28062), showing 97.95% identity. This
      species  normally causes crown rot, resulting in severe damage under dry spring 
      conditions. A pathogenicity test employed to assess the disease-causing ability 
      of the strain showed significant disease symptoms up to 57% infected spikelets. 
      The results confirmed the presence of F. pseudograminearum as a causal  agent of
      wheat crown rot in Iraq. The presence of this pathogen demands further 
      investigations to develop resistant cultivars and/or mechanical control.

PMID- 22653581
TI  - A common genetic variant of  5p15.33 is associated with risk for prostate cancer
      in the Chinese population.
AB  - Recent  evidence has suggested that single-nucleotide polymorphisms (SNPs)
      located at  5p15.33 contribute to susceptibilities for several cancer types,
      including  prostate cancer. To determine whether SNP rs402710 in this region
      plays a role  in prostate cancer, we analyzed these associations in a Chinese
      population; 251  prostate cancer patients and 273 control subjects were included
      in this  case-control study. Genotypes were determined by PCR-RFLP. We found that
      subjects carrying the CC homozygote had a decreased risk for prostrate cancer 
      compared to those carrying TT/TC genotypes (odds ratio (OR) = 0.69, 95% 
      confidence interval (CI) = 0.48-0.98, P = 0.038). Compared with the TT 
      homozygote, subjects carrying the CC homozygote also had a decreased risk for 
      prostate cancer (OR = 0.71, 95%CI = 0.51-0.99, P = 0.043). We conclude that 
      rs402710 polymorphisms in the 5p15.33 region are associated with prostate  cancer
      risk in the Chinese population. Further investigations with large  cohorts and
      done worldwide are warranted to determine whether our findings are  detected in
      other populations.

PMID- 22653582
TI  - Multiclass microarray data classification based on  confidence evaluation.
AB  - Microarray technology is becoming a powerful tool for  clinical diagnosis, as it
      has potential to discover gene expression patterns  that are characteristic for a
      particular disease. To date, this possibility has  received much attention in the
      context of cancer research, especially in tumor  classification. However, most
      published articles have concentrated on the  development of binary classification
      methods while neglected ubiquitous  multiclass problems. Unfortunately, only a
      few multiclass classification  approaches have had poor predictive accuracy. In
      an effort to improve  classification accuracy, we developed a novel multiclass
      microarray data  classification method. First, we applied a "one versus rest
      support vector  machine" to classify the samples. Then the classification
      confidence of each  testing sample was evaluated according to its distribution in
      feature space and  some with poor confidence were extracted. Next, a novel
      strategy, which we  named as "class priority estimation method based on centroid
      distance", was  used to make decisions about categories for those poor confidence
      samples. This  approach was tested on seven benchmark multiclass microarray
      datasets, with  encouraging results, demonstrating effectiveness and feasibility.

PMID- 22653583
TI  - Association of killer cell immunoglobulin-like receptors with pulmonary 
      tuberculosis in Chinese Han.
AB  - Killer cell immunoglobulin-like receptors (KIRs) are  involved in the
      pathogenesis of a variety of diseases. However, whether KIR  polymorphism is
      associated with susceptibility to pulmonary tuberculosis was  unknown. We
      examined a possible association of KIR polymorphism with susceptibility  to
      pulmonary tuberculosis in Chinese Han. We analyzed 15 KIR genes in 109  pulmonary
      tuberculosis patients and 110 healthy controls using  sequence-specific primer
      PCR analysis of genomic DNA. We found that the  frequencies of KIR2DS1, 2DS3 and
      3DS1 were significantly higher in patients  than in the control group. In
      addition, the number of subjects carrying more  than two activating KIR genes in
      the patient group was significantly higher  than in the control group. The gene
      cluster containing KIR3DS1-2DL5-2DS1-2DS5  was also significantly more frequent
      in the patient group. In conclusion, KIR  genes 2DS1, 2DS3 and 3DS1 appear to be
      associated with resistance to pulmonary  tuberculosis in the Chinese Han
      population. KIR genes apparently have a role in  resistance to pulmonary
      tuberculosis.

PMID- 22653584
TI  - A rapid and inexpensive method for isolation of total  DNA from Trichoderma spp
      (Hypocreaceae).
AB  - Extraction of high-quality genomic DNA for PCR amplification  from filamentous
      fungi is difficult because of the complex cell wall and the  high concentrations
      of polysaccharides and other secondary metabolites that  bind to or co
      precipitate with nucleic acids. We developed a modified sodium  dodecyl
      sulfate/phenol protocol, without maceration in liquid nitrogen and  without a
      final ethanol precipitation step. The A(260/280) absorbance ratios of isolated
      DNA were approximately  1.7-1.9, demonstrating that the DNA fraction is pure and
      can be used for  analysis. Additionally, the A(260/230) values  were higher than
      1.6, demonstrating negligible contamination by  polysaccharides. The DNA isolated
      by this protocol is of sufficient quality for  molecular applications; this
      technique could be applied to other organisms  that have similar substances that
      hinder DNA extraction. The main advantages of  the method are that the mycelium
      is directly recovered from culture medium and  it does not require the use of
      expensive and specialized equipment.

PMID- 22653585
TI  - Establishment and initial characterization  of SOX2-overexpressing NT2/D1 cell
      clones.
AB  - SOX2, a  universal marker of pluripotent stem cells, is a transcription factor
      that  helps control embryonic development in vertebrates; its expression persists
      in  neural stem/progenitor cells into adulthood. Considering the critical role of
      the SOX2 transcription factor in the regulation of genes required for  self
      renewal and pluripotency of stem cells, we developed and characterized SOX2
      overexpressing  NT2/D1 cell clones. Using Southern blot and semi-quantitative RT
      PCR, we  confirmed integration and expression of exogenous SOX2 in three NT2/D1 
      cell clones. Overexpression of the SOX2 gene was detected in two of  these
      clones. SOX2 overexpression in NT2/D1 cell clones resulted in  altered expression
      of key pluripotency genes OCT4 and NANOG.  Furthermore, SOX2-overexpressing
      NT2/D1 cell clones entered into  retinoic acid-dependent neural differentiation,
      even when there was elevated SOX2 expression. After 21 days of induction by
      retinoic acid, expression of  neural markers (neuroD1 and synaptophysin) was
      higher in induced cell  clones than in induced parental cells. The cell clone
      with SOX2 overexpression  had an approximately 1.3-fold higher growth rate
      compared to parental cells. SOX2 overexpression did not increase the population
      of cells undergoing  apoptosis. Taken together, we developed two SOX2
      overexpressing cell  clones, with constitutive SOX2 expression after three weeks
      of retinoic  acid treatment. SOX2 overexpression resulted in altered expression
      of  pluripotency-related genes, increased proliferation, and altered expression
      of  neural markers after three weeks of retinoic acid treatment.

PMID- 22653586
TI  - Association of TP53 gene codon 72 polymorphism with  endometriosis in Mexican
      women.
AB  - The TP53 tumor suppressor gene plays an important role  in cell cycle regulation;
      polymorphisms of this gene have been associated with  endometriosis. We examined
      the role of TP53 codon 72 polymorphism by comparing  genotypes of 235 healthy
      Mexican women (controls with surgically excluded  endometriosis) with the
      genotypes of 151 Mexican women with endometriosis. The  observed genotype
      frequencies for controls and endometriosis patients were 8  and 22% for
      proline/proline (Pro/Pro), 30 and 34% for proline/arginine  (Pro/Arg), and 62 and
      44% for arginine/arginine (Arg/Arg), respectively. We  found that odds ratio (OR)
      = 3.3; 95% confidence intervals (95%CI) = 1.7-6.4; P  = 0.0001. The association
      was also evident in the comparison of the  distributions of genotypes Pro/Pro and
      Pro/Arg in patients with  moderate-to-severe endometriosis; OR = 1.9; 95%CI =
      0.95-3.9; P = 0.049. We  suggest that genotype Pro/Pro of codon 72 polymorphism
      in TP53 contributes  significantly to endometriosis susceptibility in the Mexican
      population.

PMID- 22653587
TI  - Genome-wide identification and characterization of  simple sequence repeat loci
      in grape phylloxera, Daktulosphaira vitifoliae.
AB  - A genome-wide sequence search was conducted to  identify simple sequence repeat
      (SSR) loci in phylloxera, Daktulosphaira  vitifoliae, a major grape pest
      throughout the world. Collectively,  1524 SSR loci containing mono-, di-, tri-,
      tetra-, penta-, and hexanucleotide  motifs were identified. Among them,
      trinucleotide repeats were the most  abundant in the phylloxera genome (34.4%),
      followed by hexanucleotide (20.4%)  and dinucleotide (19.6%) repeats. Mono-,
      tetra- and pentanucleotide repeats  were found at a frequency of 1.3, 11.2 and
      12.9%, respectively. The abundance  and inherent variations in SSRs provide
      valuable information for developing  molecular markers. The high levels of
      allelic variation and codominant features  of SSRs make this marker system a
      useful tool for genotyping, diversity  assessment and population genetic studies
      of reproductive characteristics of  phylloxera in agricultural and natural
      populations.

PMID- 22653588
TI  - Genetic progress in the UNB-2U population of popcorn  under recurrent selection
      in Rio de Janeiro, Brazil.
AB  - As part of the Universidade Estadual do Norte  Fluminense recurrent selection
      program of popcorn, we evaluated full-sib  families of the sixth cycle of
      recurrent selection and estimated genetic  progress for grain yield and expansion
      capacity. We assessed 200 full-sib  families for 10 agronomic traits, in a
      randomized block design, with two  replications within sets in two environments:
      Campos dos Goytacazes and  Itaocara, in the State of Rio de Janeiro, Brazil.
      There were significant  differences for families/"sets" for all traits,
      indicating genetic variability  that could be exploited in future cycles. In the
      selection of superior  progenies, the Mulamba and Mock index gave the best gains
      for popping expansion  (PE) and grain yield (GY), with values of 10.97 and
      15.30%, respectively, using  random economic weights. By comparing the evolution
      of the means obtained for  PE and GY in the cycles C(0), C(1), C(2), C(3), C(4),
      C(5), and predicted for C(6), a steady increase was observed for both  PE and GY,
      with the addition of 1.71 mL/g (R(2) = 0.93) and 192.87 kg/ha (R(2) = 0.88),
      respectively, in each cycle. Given the good  performance of this popcorn
      population in successive cycles of intrapopulation  recurrent selection, we
      expect that a productive variety with high expansion  capacity will soon be
      available for producers in the north and northwest  regions of Rio de Janeiro
      State, Brazil.

PMID- 22653590
TI  - Low prevalence of glucokinase  gene mutations in gestational diabetic patients
      with good glycemic control.
AB  - Glucokinase  (GCK) plays a key role in glucose homeostasis. Gestational diabetes
      mellitus  increases the risk of gestational complications in pregnant women and
      fetuses.  We screened for mutations in coding and flanking regions of the GCK
      gene  in pregnant women with or without gestational diabetes in a Brazilian 
      population. A sample of 200 pregnant women classified as healthy (control, N = 
      100) or with gestational diabetes (N = 100) was analyzed for mutations in the GCK
      gene. All gestational diabetes mellitus patients had good glycemic control 
      maintained by diet alone and no complications during pregnancy. Mutations were 
      detected by single-strand conformation polymorphism and DNA sequencing.  Thirteen
      of the 200 subjects had GCK gene mutations. The mutations  detected were in
      intron 3 (c.43331A>G, new), intron 6 (c.47702T>C,  rs2268574), intron 9
      (c.48935C>T, rs2908274), and exon 10 (c.49620G>A,  rs13306388). None of these GCK
      mutations were found to be significantly  associated with gestational diabetes
      mellitus. In summary, we report a low  frequency of GCK mutations in a pregnant
      Brazilian population and  describe a new intronic variation (c.43331A>G, intron
      3). We conclude that  mutations in GCK introns and in non-translatable regions of
      the GCK gene  do not affect glycemic control and are not correlated with
      gestational diabetes  mellitus.

PMID- 22653589
TI  - Evaluation of the effects of  androgen receptor gene trinucleotide repeats and
      prostate-specific antigen gene  polymorphisms on prostate cancer.
AB  - The  number of trinucleotide repeats [CAG (coding for polyglutamine), GGC (coding
      for polyglycine)] in the first exon of the androgen receptor (AR) gene and 
      prostate-specific antigen (PSA) gene androgen response element I A/G 
      polymorphism are both related to prostate cancer prognosis. We investigated 
      whether these genomic changes occur in the AR and PSA genes, which are usually 
      found in individuals with prostate cancer, of Turkish patients and to find out 
      their distribution in the population. We used PCR and PCR-RFLP assays for AR  and
      PSA genes, respectively, to detect molecular changes in 44 prostate cancer 
      patients. Our findings indicate that individuals with prostate cancer tend to 
      have around 18 CAG trinucleotide repeats. We observed significant differences 
      between 22 controls, 33 benign prostate hyperplasia (BPH) patients and 44 
      adenocarcinoma patients for long CAG repeats. However, we did not find any 
      significant differences in GGC repeats between controls, BPH and adenocarcinoma 
      patients (P = 0.408). We also did not observe significant differences in the  PSA
      A/G polymorphism frequency between controls, BPH and adenocarcinoma  patients (P
      = 0.483). In conclusion, CAG and GGC repeats in the AR and PSA gene 
      polymorphisms may be associated with prostate cancer risk and BPH in the  Turkish
      population.

PMID- 22653591
TI  - Stable expression and  integrated hepatitis B virus genome in a human hepatoma
      cell line.
AB  - HepG2.2.15  cell is a widely used cell model for studying HBV (hepatitis B virus)
      in  vitro. In these cells, the HBV genome is integrated in several sites of 
      HepG2 cellular DNA. These multiple copies may have some influence on the 
      cellular processes. We constructed a new plasmid, pSEH-Flag-HBV, and  transfected
      it into HepG2 cells, and then screened it with hygromycin. We then  used ELISA,
      PCR, and RT-PCR to detect the expression of HBV in these cell  lines. A cell line
      that stably expressed hepatitis B e antigen (HBeAg) and  hepatitis B surface
      antigen (HBsAg) was established. Using Southern blotting  analysis, we found that
      the HBV genome was integrated as a single copy in the  cellular DNA. This cell
      line will be a useful alternative model for HBV  studies.

PMID- 22653592
TI  - Development of 18  microsatellite loci for the freshwater snail Bellamya
      aeruginosa (Mollusca,  Gastropoda).
AB  - Although  it is a major freshwater gastropod species, genetic diversity of
      Bellamya  aeruginosa was completely unknown. Eighteen microsatellite loci were 
      isolated and characterized from (AC)(15)-enriched genomic  libraries of the
      freshwater snail B. aeruginosa. Most of the 18 loci  were successfully amplified
      and high polymorphic information content values  were found, ranging from 0.244
      to 0.792 (mean 0.541). The number of alleles per  locus ranged from 5 to 13 (mean
      8.8), the expected heterozygosity varied from  0.347 to 0.950 (mean 0.815) and
      the observed heterozygosity varied from 0.087  to 0.782 (mean 0.431). Eight loci
      showed significant deviation from  Hardy-Weinberg equilibrium after Bonferroni's
      correction and no significant  genotypic linkage disequilibrium was detected
      between most locus pairs, except  for TXH79-TXH97 and TXH113-TXH121. These 18
      polymorphic microsatellite loci  should be useful for population genetics
      analysis and species identification of Bellamya.

PMID- 22653593
TI  - A novel mutation of the MFN2 gene in a Chinese family  with Charcot-Marie-Tooth
      disease.
AB  - Charcot-Marie-Tooth (CMT) is a group of clinically and  genetically heterogeneous
      inherited neuromuscular disorders. At present, more  than 30 loci have been
      reported to be associated with CMT disease; point  mutations in the mitofusin 2
      (MFN2) gene is one of the most common causes. We  studied a Chinese family with
      CMT disease in which the phenotype of affected  individuals varied, and the
      weakness condition of the distal legs in males,  except the proband, was less
      severe than in females in this family. Linkage  analysis and PCR sequencing
      revealed a missense mutation (NM_014874.3:c.1066  A>G) in the MFN2 gene,
      resulting in an animo acid substitution of threonine  to alanine in condon 356
      (Thr356Ala). This is a novel phenotype and mutation  for CMT family.

PMID- 22653594
TI  - Mutations in NPHS1 in a  Chinese child with congenital nephrotic syndrome.
AB  - Since  the identification of the NPHS1 gene, which encodes nephrin, various 
      investigators have demonstrated that the NPHS1 mutation is a frequent  cause of
      congenital nephrotic syndrome (CNS); it is found in 98% of Finnish  children with
      this syndrome and in 39-80% of non-Finnish cases. In China,  compound
      heterozygous mutations in the NPHS1 gene have been identified  in two Chinese
      families with CNS. To our knowledge, however, whether or not NPHS1 is the
      causative gene in sporadic Chinese CNS cases has not been  established. We
      identified a homozygous mutation of NPHS1, 3250insG  (V1084fsX1095), in a Chinese
      child with sporadic CNS. This finding leads us to  suggest that NPHS1 mutations
      are also present in sporadic Chinese CNS  cases. This gives additional support
      for the necessity for genetic examination  of mutations in the NPHS1 gene in
      Chinese children with sporadic CNS.

PMID- 22653595
TI  - Seventeen polymorphic microsatellite markers developed  for the Javelin goby,
      Synechogobius hasta (Gobiidae).
AB  - Synechogobius hasta is an important commercial marine fish with  distinctive
      features of rapid growth and short lifespan. We isolated and  characterized 17
      microsatellite markers for S. hasta using a (GT)(13)-enriched  genomic library.
      Polymorphism was assessed in 48 individuals from a single  population collected
      from the northern coastal waters of the Yellow Sea. The  number of alleles per
      locus ranged from 2 to 23, with a mean of 11.3. The  observed and expected
      heterozygosities ranged from 0.130 to 1.000 and from  0.123 to 0.939, with means
      of 0.758 and 0.774, respectively. Fourteen of 17  loci conformed to Hardy
      Weinberg equilibrium and no significant linkage  disequilibrium between locus
      pairs was detected. These microsatellite markers  will be useful for population
      genetic structure analyses.

PMID- 22653596
TI  - Development of microsatellite markers for the small  yellow croaker Larimichthys
      polyactis (Sciaenidae) by cross-species  amplification.
AB  - The small yellow croaker (Larimichthys polyactis)  is a highly valued fish for
      human consumption found in the Western Pacific that  was considered endangered
      until recently because of overfishing. We selected  microsatellite markers for
      this species from markers developed for Miichthys  miiuy, also of the family
      Sciaenidae. Among 43 markers polymorphic for M.  miiuy, 11 were found to be
      polymorphic for L. polyactis.  Characterization of these 11 loci was made based
      on 30 L. polyactis individuals  collected by trawling in the Zhoushan Fishing
      Ground, Zhejiang Province, China.  Total genomic DNA was isolated from fin clips.
      The number of alleles per locus  ranged from 4 to 10, with a mean of 5.82, while
      the effective number of alleles  ranged from 1.64 to 10.00, with a mean of 3.22.
      Observed and expected  heterozygosities ranged from 0.17 to 0.72 and from 0.39 to
      0.81, respectively.  Significant deviation from Hardy-Weinberg equilibrium was
      found at four loci,  after applying Bonferroni's correction. There was no
      significant association  between any of the pairs of microsatellite loci, hence
      allelic variation at  these loci was considered independent. These 11 polymorphic
      microsatellite loci  will be useful for genetic diversity analysis and molecular
      assisted breeding  for L. polyactis.

PMID- 22653597
TI  - Molecular characterization of  a mariner-like element in the Atta sexdens
      rubropilosa genome.
AB  - Mobile  elements are widely present in eukaryotic genomes. They are repeated DNA 
      segments that are able to move from one locus to another within the genome.  They
      are divided into two main categories, depending on their mechanism of 
      transposition, involving RNA (class I) or DNA (class II) molecules. The mariner
      like  elements are class II transposons. They encode their own transposase, which
      is  necessary and sufficient for transposition in the absence of host factors.
      They  are flanked by a short inverted terminal repeat and a TA dinucleotide
      target  site, which is duplicated upon insertion. The transposase consists of two
      domains,  an N-terminal inverted terminal repeat binding domain and a C-terminal 
      catalytic domain. We identified a transposable element with molecular 
      characteristics of a mariner-like element in Atta sexdens rubropilosa genome.
      Identification started from a PCR with degenerate primers and queen  genomic DNA
      templates, with which it was possible to amplify a fragment with mariner
      transposable-element homology. Phylogenetic analysis demonstrated that this 
      element belongs to the mauritiana subfamily of mariner-like  elements and it was
      named Asmar1. We found that Asmar1 is  homologous to a transposon described from
      another ant, Messor bouvieri.  The predicted transposase sequence demonstrated
      that Asmar1 has a  truncated transposase ORF. This study is part of a molecular
      characterization  of mobile elements in the Atta spp genome. Our finding of
      mariner-like  elements in all castes of this ant could be useful to help
      understand the  dynamics of mariner-like element distribution in the Hymenoptera.

PMID- 22653598
TI  - Association of GSTM1 and GSTT1 with ageing in auto  repair shop workers.
AB  - We evaluated the possible influence of  glutathione S-transferase mu (GSTM1) and
      glutathione S-transferase theta  (GSTT1) genes on genetic damage due to
      occupational exposure, which  contributes to accelerate ageing. This study was
      conducted on 120 car auto  repair workshop workers exposed to occupational
      hazards and 120 controls  without this kind of exposure. The null and non-null
      genotypes of GSTM1 and  GSTT1 genes were determined by multiplex PCR.
      Micronucleus frequency, Comet  tail length and relative telomere length
      differences between the null and  non-null genotypes of the GSTM1 gene were
      significantly greater in the exposed  group. Lack of GSTT1 did not affect the
      damage biomarkers significantly (P >  0.05), while lack of GSTM1 was associated
      with greater susceptibility to  genomic damage due to occupational exposure. It
      was concluded that early ageing  is under the influence of these genes and the
      environmental and  socio-demographic factors. Duration of working time was
      significantly  associated with micronucleus frequency, Comet tail length and
      relative telomere  length.

PMID- 22653599
TI  - Expression of Pink1 with alpha-synuclein in the dopaminergic  neurons of
      Drosophila leads to increases in both lifespan and healthspan.
AB  - Overexpression  of the gene coding for alpha-synuclein has been shown to be an
      inherited cause of Parkinson disease. Our  laboratory has previously co-expressed
      the parkin and Pink1 genes  to rescue alpha-synuclein-induced  phenotypes within
      a Drosophila model. To further investigate the effect  of Pink1 in this model, we
      performed longevity and behavioral studies  using several drivers to express the
      alpha-synuclein and Pink1 genes.  Our findings showed that overexpression of
      Pink1 and overexpression of Pink1 with alpha-synuclein resulted in an increased
      lifespan when driven with the TH-Gal4 transgene.  This increase in longevity was
      accompanied by an increased healthspan, as  measured by mobility over time,
      suggesting that this is an example of improved  functional aging. Our results
      indicate that, in the dopaminergic cells targeted  by TH-Gal4, increased
      expression of alpha-synuclein and Pink1 together  have a synergistic effect,
      allowing for enhanced protection and increased  survival of the organism.

PMID- 22653600
TI  - Rapid isolation and  characterization of polymorphic microsatellite loci in the
      mud crab, Scylla  paramamosain (Portunidae).
AB  - Scylla paramamosain is a widespread and commercially important species of coastal
      marine crab. We identified 13 polymorphic microsatellite loci from a genome
      library constructed with 5'-anchored PCR method. Thirty-two S. paramamosain from
      the East China Sea were used to analyze the characteristics of these loci. The
      number of alleles per locus ranged from 3 to 8, with a mean of 5.923. Observed
      and expected heterozygosities ranged from 0.500 to 0.875 and from 0.500 to 0.859,
      respectively. Eleven of the 13 loci were highly polymorphic (polymorphic
      information content >0.5). All of the 13 novel loci were in Hardy-Weinberg
      equilibrium after Bonferroni's correction (P < 0.0038). There was no null allele,
      stuttering errors or evidence of allelic dropout in any of the loci analyzed by
      MICRO-CHECKER. According to pairwise tests, no significant linkage disequilibrium
      was found among the 13 loci (P < 0.0038, adjusted value). These novel developed
      microsatellites will be useful for studies of genetic variation, population
      structure, conservation genetics, and molecular-assisted selective breeding of S.
      paramamosain.

PMID- 22653601
TI  - Comparison of a retrotransposon-based marker with microsatellite markers  for
      discriminating accessions of Vitis vinifera.
AB  - Identification and knowledge concerning genetic  diversity are fundamental for
      efficient management and use of grapevine  germplasm. Recently, new types of
      molecular markers have been developed, such  as retrotransposon-based markers.
      Because of their multilocus pattern,  retrotransposon-based markers might be able
      to differentiate grapevine accessions  with just one pair of primers. In order to
      evaluate the efficiency of this type  of marker, we compared retrotransposon
      marker Tvv1 with seven  microsatellite markers frequently used for genotyping of
      the genus Vitis (VVMD7,  VVMD25, VVMD5, VVMD27, VVMD31, VVS2, and VZAG62). The
      reference population that  we used consisted of 26 accessions of Vitis, including
      seven European  varieties of Vitis vinifera, four North American varieties and
      hybrids  of Vitis labrusca, and 15 rootstock hybrids obtained from crosses of 
      several Vitis species. Individually, the Tvv1 and the group of  seven SSR markers
      were capable of distinguishing all accessions except 'White  Niagara' compared to
      'Red Niagara'. Using the Structure software, the  retrotransposon marker Tvv1
      generated two clusters: one with V.  vinifera plus North American varieties and
      the other comprising rootstocks.  The seven SSR markers generated five clusters:
      V. vinifera, the North  American varieties, and three groups of rootstock
      hybrids. The percentages of  variation explained by the first two components in
      the principal coordinate  analysis were 65.21 (Tvv1) and 50.42 (SSR markers)
      while the Mantel  correlation between the distance matrixes generated by the two
      types of markers  was 42.5%. We conclude that the Tvv1 marker is useful for DNA 
      fingerprinting, but it lacks efficiency for discrimination of structured  groups.

PMID- 22653602
TI  - Development and characterization of nine polymorphic  microsatellites for the
      small brown planthopper Laodelphax striatellus (Hemiptera:  Delphacidae).
AB  - Nine microsatellite loci were isolated from the genome  of Laodelphax striatellus
      (Homoptera: Delphacidae) by constructing (TC)(6)(AC)(5) and (AG)(6)(AC)(5)
      compound SSR-enriched libraries using  suppression-PCR procedures. These loci
      were found to be highly polymorphic,  with 13 to 30 alleles per locus in the
      three populations that we investigated  (Jiangsu, Shandong and Zhejiang). The
      observed and expected heterozygosities  ranged from 0.255 to 0.833 and 0.392 to
      0.929, respectively. These  microsatellite markers can be used for the study of
      population genetic  structure and genetic diversity of L. striatellus.

PMID- 22653603
TI  - An improved protocol and a new grinding device for  extraction of genomic DNA
      from microorganisms by a two-step extraction procedure.
AB  - Current protocols to extract genomic DNA from microorganisms  are still
      laborious, tedious and costly, especially for the species with thick  cell walls.
      In order to improve the effectiveness of extracting DNA from  microbial samples,
      a novel protocol, defined as two-step extraction method,  along with an improved
      tissue-grinding device, was developed. The protocol  included two steps,
      disruption of microbial cells or spores by grinding the  sample together with
      silica sand in a new device and extraction of DNA with an  effective buffer
      containing cell lysis chemicals. The device was prepared by  using a commercial
      electric mini-grinder, adapted with a grinding stone, and a  sample cup processed
      by lathing from a polytetrafluoroethylene rod. We tested  the method with
      vegetative cells of four microbial species and two microbial  spores that have
      thick cell walls and are therefore hard to process; these  included Escherichia
      coli JM109, Bacillus subtilis WB600, Sacchromyces  cerevisiae INVSc1, Trichoderma
      viride AS3.3711, and the spores of S.  cerevisiae and T. viride, respectively,
      representing Gram-positive  bacteria, Gram-negative bacteria, yeast, filamentous
      fungi. We found that this  new method and device extracted usable quantities of
      genomic DNA from the  samples. The DNA fragments that were extracted exceeded 23
      kb. The target  sequences up to about 5 kb were successfully and exclusively
      amplified by PCR  using extracted DNA as the template. In addition, the DNA
      extraction was  finalized within 1.5 h. Thus, we conclude that this two-step
      extraction method  is an effective and improved protocol for extraction of
      genomic DNA from  microbial samples.

PMID- 22653604
TI  - Recombinant expression and characterization of an endoglucanase III  (cel12a)
      from  Trichoderma harzianum (Hypocreaceae)  in the yeast Pichia pastoris.
AB  - Filamentous fungi from the genus Trichoderma have  been widely investigated due
      to their considerable production of important  biotechnological enzymes. Previous
      studies have demonstrated that the T.  harzianum strain IOC-3844 has a high
      degree of cellulolytic activity. After  excluding the native signal peptide, the
      open reading frame of the T.  harzianum endoglucanase III enzyme was cloned in
      the expression vector  pPICZalphaA, enabling protein secretion to the  culture
      medium. The recombinant plasmid was used to transform Pichia  pastoris.
      Recombinant expression in the selected clone yielded 300 mg pure  enzyme per
      liter of induced medium. The recombinant enzyme proved to be active  in a
      qualitative analysis using Congo red. A quantitative assay, using 
      dinitrosalicylic acid, revealed a high degree of activity at pH 5.5 and around 
      48 degrees C. This information contributes to our understanding of the
      cellulolytic  repertory of T. harzianum and the determination of a set of enzymes
      that  can be incorporated into mixes for second-generation ethanol production.

PMID- 22653605
TI  - Application of functional genomic information to  develop efficient EST-SSRs for
      the chicken (Gallus gallus).
AB  - Many years of domestication and breeding have given  rise to the wide range of
      chicken breeds that exist today; however, an  increasing number of local chicken
      breeds are under threat of extinction. A  comprehensive characterization of
      chicken markers (especially type I markers)  is needed to monitor and conserve
      genetic diversity in this species. The  explosion of genomics and functional
      genomics information in recent years has  opened new possibilities for the
      generation of molecular markers. We analyzed a  large number of expressed
      sequence tags (ESTs) to test the possibility of using  EST-derived microsatellite
      markers for investigating the Gallus gallus genome.  Chromosomal locations for
      the majority of these SSRs were predicted. Of the  31,576 unigenes assembled from
      the 544,150 redundant EST sequences, 1757 SSR  markers were discovered on 1544
      ESTs, using the SSRLocator software, with an  average density of 28.7 kb per SSR.
      The dimer motifs were the most frequent  (46.38%), followed by trimeric (38.58%),
      tetrameric (10.19%), pentameric  (4.5%), and hexameric (<1%) markers. Different
      from the case for cattle and  sheep, AT/TA was the most abundant dimeric repeat,
      accounting for 41.71% of all  dimeric repeats in the chicken ESTs. The EST-SSR
      distribution was not uniform  among the chromosomes; the majority of the EST-SSRs
      were located on chromosomes  GGA2 and GGA10. We found that most of the EST-SSRs
      are involved in positive  regulation of cellular and metabolic processes. This is
      the first time that EST  sequences have been mined to find chicken
      microsatellites. On average, 3.8% of  the G. gallus UniGene sequences could be
      exploited for development of  EST-SSRs, indicating a good source for molecular
      markers as well as for  functional genome analysis.

PMID- 22653606
TI  - Retraction: Novel azithromycin derivatives with the C-4" bisamide side chains:
      synthesis and biological evaluation against gram-positive bacteria.

PMID- 22653607
TI  - Binding mechanism between Hsp90 and Sgt1 explored by homology modeling and
      molecular dynamics simulations in rice.
AB  - The Hsp90 (for heat shock protein90) and the Sgt1 (for suppressor of the G2
      allele of skp1) are widely distributed in animals, yeast, and plants. The former
      functions as molecular chaperon activating a series of client proteins, the
      latter functions as an adaptor protein participating in multiple biological
      processes such as immunity response through interactions with different protein
      complexes. In the present study, we have constructed a homology model of Hsp90
      Sgt1 complex in rice based on a recently resolved structure from barley and
      Arabidopsis to explore its binding mechanisms and to understand the detailed
      interaction profile. A total of 20 ns explicit solvent molecular dynamics
      simulations combined with MM-GBSA computations and virtual alanine scanning were
      performed for the modeled complex. In the final structure, three strong salt
      bridges were found between OsHsp90 and OsSgt1, D217(OsHsp90)-K186(OsSgt1),
      D218(OsHsp90)-K237(OsSgt1) and K161(OsHsp90)-E239(OsSgt1). Besides, residue Y173
      of OsSgt1 played a vital role in the interactions with OsHsp90, the detailed
      interactions were discussed. These results would help us understand the critical
      features determining the Hsp90-Sgt1 binding process.

PMID- 22653608
TI  - Photodissociation of a ruthenium(II) arene complex and its subsequent
      interactions with biomolecules: a density functional theory study.
AB  - The piano-stool Ru(II) arene complex [(eta6-benz)Ru(bpm)(py)]2+ (benz = benzene,
      bpm = 2,2'-bipyrimidine, and py = pyridine), which is conventionally nonlabile
      (on a timescale and under conditions relevant for biological reactivity), can be
      activated by visible light to selectively photodissociate the monodentate ligand
      (py). In the present study, the aquation and binding of the photocontrolled
      ruthenium(II) arene complex [(eta6-benz)Ru(bpm)(py)]2+ to various biomolecules
      are studied by density functional theory (DFT) and time-dependent DFT (TDDFT).
      Potential energy curves (PECs) calculated for the Ru-N (py) bonds in [(eta6
      benz)Ru(bpm)(py)]2+ in the singlet and triplet state give useful insights into
      the photodissociation mechanism of py. The binding energies of the various
      biomolecules are calculated, which allows the order of binding affinities among
      the considered nuleic-acid- or protein-binding sites to be discerned. The
      kinetics for the replacement of water in the aqua complex with biomolecules is
      also considered, and the results demonstrate that guanine is superior to other
      biomolecules in terms of coordinating with the Ru(II) aqua adduct, which is in
      reasonable agreement with experimental observations.

PMID- 22653609
TI  - Ribavirin, a nucleoside with potential insecticidal activity.
AB  - BACKGROUND: The triazole-based antiviral nucleoside ribavirin exhibited
      significant in vitro insecticidal effects against Spodoptera litura, a finding
      that has prompted further investigations into its in vivo insecticidal properties
      and mode of action against this insect pest. RESULTS: Ribavirin showed delayed
      insecticidal effects on third-instar larvae of S. litura at a concentration of 1
      mg mL(-1) . When incorporated into an artificial diet, ribavirin caused various
      effects, depending on the concentration used. Compared with controls, food intake
      was lower, larval growth was reduced and larval development prolonged. Pupae
      weight was reduced, and adult morphology was also affected. Relative to the
      untreated group, treated groups showed higher mortality at larval and pupal
      stages, which was generally caused by moult disruption. Results of this study
      with ribavirin resemble those found in treatment with insect growth regulators.
      CONCLUSION: This work shows that ribavirin merits further study as a lead
      compound in a novel class of potential insect control agents or for managing
      field populations of Lepidoptera pests on cruciferous crops.

PMID- 22653610
TI  - Chemical composition and sensory quality of bovine milk as affected by type of
      forage and proportion of concentrate in the feed ration.
AB  - BACKGROUND: The objective of this study was to investigate how some small changes
      in the forage content of maize and lucerne silage and in the ration between
      forage and concentrate in the diet of dairy cows affect milk quality. Milk
      quality was assessed by quantitative descriptive sensory analysis and by analysis
      of tocopherols and carotenoids as well as fatty acid composition. RESULTS:
      Changing the ratio between maize silage and lucerne silage from 5:1 to 2:1
      increased milk fat content of carotenoids (23-27%) and C18:3 n3 (15%), and
      reduced stale aroma and creamy flavour. Increasing the proportion of concentrates
      in the feed ration from 0.2 to 0.4 increased energy corrected milk yield (26%),
      reduced fat content (-10%), increased C18 fatty acids (8-62%) and reduced C16 (
      20%) content in milk fat. In addition, this milk type was described by the
      sensory panel as less oily, less saturated and less yellow. The changes in milk
      composition were related to differences in feed composition. CONCLUSION: The
      study revealed the potential to produce milk with a distinct composition and
      sensory quality based on even small changes in the feed composition that are
      straightforward to implement by farmers.

PMID- 22653612
TI  - Oral plasmablastic lymphoma in an HIV-positive patient with an unusual survival
      rate.

PMID- 22653613
TI  - Effect of graphene oxide on undifferentiated and retinoic acid-differentiated SH
      SY5Y cells line.
AB  - Graphene oxide (GO), has created an unprecedented opportunity for development and
      application in biology, due to its abundant functional groups and well water
      solubility. Recently, the potential toxicity of GO in the environment and in
      humans has garnered more and more attention. In this paper, we systematically
      studied the cytotoxicity of GO nanosheets via examining the effect of GO on the
      morphology, viability and differentiation of a human neuroblastoma SH-SY5Y cell
      line, which was an ideal model used to study neuronal disease in vitro. The
      results suggested that GO had no obvious cytotoxicity at low concentration (<80
      MUg mL(-1)) for 96 h, but the viability of cells exhibited dose- and time
      dependent decreases at high concentration (>= 80 MUg mL(-1)). Moreover, GO did
      not induce apoptosis. Very interestingly, GO significantly enhanced the
      differentiation of SH-SY5Y induced-retinoic acid (RA) by evaluating neurite
      length and the expression of neuronal marker MAP2. These data provide a promising
      application for neurodegenerative diseases.

PMID- 22653614
TI  - The effects of local vanadium treatment on angiogenesis and chondrogenesis during
      fracture healing.
AB  - This study quantified the effects of local intramedullary delivery of an organic
      vanadium salt, which may act as an insulin-mimetic on fracture healing. Using a
      BB Wistar rat femoral fracture model, local vanadyl acetylacetonate (VAC) was
      delivered to the fracture site and histomorphometry, mechanical testing, and
      immunohistochemistry were performed. Callus percent cartilage was 200% higher at
      day 7 (p < 0.05) and 88% higher at day 10 (p < 0.05) in the animals treated with
      1.5 mg/kg of VAC. Callus percent mineralized tissue was 37% higher at day 14 (p <
      0.05) and 31% higher at day 21 (p < 0.05) in the animals treated with 1.5 mg/kg
      of VAC. Maximum torque to failure was 104% and 154% higher at 4 weeks post
      fracture (p < 0.05) for the healing femurs from the VAC-treated (1.5 and 3.0
      mg/kg) animals. Animals treated with other VAC doses demonstrated increased
      mechanical parameters at 4 weeks (p < 0.05). Immunohistochemistry detected 62%
      more proliferating cells at days 7 (p < 0.05) and 94% more at day 10 (p < 0.05)
      in the animals treated with 1.5 mg/kg VAC. Results showed 100% more vascular
      endothelial growth factor-C (VEGF-C) positive cells and 80% more blood vessels at
      day 7 (p < 0.05) within the callus subperiosteal region of VAC-treated animals
      (1.5 mg/kg) compared to controls. The results suggest that local VAC treatment
      affects chondrogenesis and angiogenesis within the first 7-10 days post-fracture,
      which leads to enhanced mineralized tissue formation and accelerated fracture
      repair as early as 3-4 weeks post-fracture.

PMID- 22653615
TI  - Factors related to weight loss attempt among Dominican immigrants.
AB  - To assess weight loss attempt among a Latino immigrant population from the
      Dominican Republic we analyzed data on 585 overweight and obese Dominicans from a
      cross-sectional survey using Chi-square statistics, Student's t-tests, and
      logistic regression models. We found 58% of the overweight and obese tried to
      lose weight. Female gender (OR 2.28, CI 1.53-3.39), overweight perception (OR
      2.37, CI 1.57-3.60) and weight loss advice from health professionals (OR 1.90, CI
      1.24-2.91) were strongly associated with weight loss attempt. Individuals with
      diabetes were more likely to receive advice to lose weight (OR 2.58, CI 1.18
      5.63; yet, they were more satisfied with their weight (40.5 vs. 27.8%, p <
      0.021), and no difference in their weight loss attempt (p = 0.849) was detected
      compared to individuals without diabetes. We conclude a significant proportion of
      overweight and obese Dominican immigrants do not attempt to lose weight.
      Overweight perception and, except among individuals with diabetes, weight loss
      advice were strong inducements to weight loss attempt.

PMID- 22653616
TI  - Association between serum thymosin beta4 levels of rheumatoid arthritis patients
      and disease activity and response to therapy.
AB  - The aim of this study was to evaluate whether thymosin beta4 (Tbeta4) levels are
      increased in the serum of rheumatoid arthritis (RA) patients, and if this
      increase is associated with RA disease activity and resistance to treatment.
      Blood samples from 40 patients with RA were collected at baseline and 6 months
      after starting treatment with disease-modifying antirheumatic drugs (DMARD)
      and/or tumor necrosis factor (TNF)-alpha blocker. Serum levels of Tbeta4 were
      measured by ELISA. Tbeta4 levels (mean +/- standard deviation) in RA patients
      were significantly (approximately tenfold) higher than in healthy controls (577.4
      +/- 67.92 vs. 56.61 +/- 5.72 ng/mL). Serum Tbeta4 levels in patients with severe
      disease activity before therapy were slightly higher than in patients with
      moderate disease activity (662.4 +/- 491.5 vs. 462.5 +/- 305.3 ng/ml, P > 0.05).
      Tbeta4 levels were significantly associated with disease activity according to
      the 28-joint Disease Activity Score. The mean Tbeta4 level at baseline in the
      DMARD treatment group was significantly lower than in the DMARD + TNF-alpha
      blocker treatment group. Tbeta4 levels were increased in the serum of patients
      with RA and were positively associated with disease activity. Levels of Tbeta4
      may also be relevant in determining or predicting resistance to RA treatment.
      Further studies are necessary to determine if Tbeta4 is an appropriate
      therapeutic target for controlling inflammation associated with RA.

PMID- 22653617
TI  - Effects of buprofezin and diflubenzuron on various developmental stages of Asian
      citrus psyllid, Diaphorina citri.
AB  - BACKGROUND: Diaphorina citri populations in Florida are developing resistance to
      commonly used neurotoxic insecticides. Alternatives to neurotoxins, such as
      insect growth regulators, are needed to control this season-long subtropical pest
      to prevent or delay development of insecticide resistance. In the present
      investigation, two insect growth regulators (IGRs), buprofezin and diflubenzuron,
      were evaluated against various developmental stages of D. citri. RESULTS: The 0-1
      day-old D. citri eggs were more susceptible to buprofezin and diflubenzuron than
      the 3-4-day-old eggs. Adult emergence was completely suppressed by treating first
      or third-instar nymphs with buprofezin or diflubenzuron at 30-240 or 23-184 ug
      mL(-1) rates respectively. Treatment of fifth-instar nymphs with diflubenzuron at
      a rate of 184 ug mL(-1) and with buprofezin at 30-240 ug mL(-1) rates resulted in
      approximately 20 and 15-80% reductions in adult emergence respectively. The mean
      number of eggs per plant was reduced at 5 days after topical treatment with
      diflubenzuron. Mean egg hatch per plant was reduced at 5 and 6-15 days after
      topical treatments with buprofezin and diflubenzuron respectively. CONCLUSION:
      Buprofezin and diflubenzuron effectively suppressed D. citri adult emergence. D.
      citri were more susceptible as early (first-third-instar) than late (fifth
      instar) nymphs. Both IGRs inhibited egg production and egg hatch. Reduction in
      the number of subsequent offspring suggests reduced vertical transmission of
      Candidatus Liberibacter asiaticus, the pathogen thought to cause citrus greening
      disease. The present results indicate that both IGRs tested here should be
      effective tools for rotation in insecticide-based D. citri management programs.

PMID- 22653618
TI  - Using preventive home monitoring to reduce hospital admission rates and reduce
      costs: a case study of telehealth among chronic obstructive pulmonary disease
      patients.
AB  - We studied whether preventive home monitoring of patients with chronic
      obstructive pulmonary disease (COPD) could reduce the frequency of hospital
      admissions and lower the cost of hospitalization. Patients were recruited from a
      health centre, general practitioner (GP) or the pulmonary hospital ward. They
      were randomized to usual care or tele-rehabilitation with a telehealth monitoring
      device installed in their home for four months. A total of 111 patients were
      suitable for inclusion and consented to be randomized: 60 patients were allocated
      to intervention and three were lost to follow-up. In the control group 51
      patients were allocated to usual care and three patients were lost to follow-up.
      In the tele-rehabilitation group, the mean hospital admission rate was 0.49 per
      patient per 10 months compared to the control group rate of 1.17; this difference
      was significant (P = 0.041). The mean cost of admissions was ?3461 per patient in
      the intervention group and ?4576 in the control group; this difference was not
      significant. The Kaplan-Meier estimates for time to hospital admission were
      longer for the intervention group than the controls, but the difference was not
      significant. Future work requires large-scale studies of prolonged home
      monitoring with more extended follow-up.

PMID- 22653619
TI  - Use of honey bees (Apis mellifera L.) to detect the presence of Mediterranean
      fruit fly (Ceratitis capitata Wiedemann) larvae in Valencia oranges.
AB  - BACKGROUND: When fruit deteriorates a characteristic profile of volatile
      chemicals is produced that is different from that produced by healthy fruits. The
      identification of such chemicals allows the possibility of monitoring the fruit
      for early signs of deterioration with biological sensors. The use of honey bees
      and other insects as biological sensors is well known. This study aimed to
      identify the volatiles produced by oranges infested with larvae of the
      Mediterranean fruit fly and to test the ability of honey bees, conditioned to
      this volatile chemical profile, to detect such oranges. RESULTS: Seventeen
      compounds that were present in higher concentrations in the volatile profiles of
      infested oranges than in those of insect-free fruits were mixed at the same
      relative concentrations as those in the collected volatiles of infested oranges.
      The synthetic mixture was used to train honey bees by classical Pavlovian
      conditioning and subsequent tests showed that they were then able to discriminate
      between medfly-infested and uninfested oranges. CONCLUSION: This study
      demonstrates an innovative way of detecting, at an early stage, the symptoms of
      damage to oranges by the Mediterranean fruit fly.

PMID- 22653621
TI  - Why do walk-in patients prefer a busy urban emergency department during office
      hours?  A pilot survey of 200 consecutive patients from Switzerland.
AB  - PRINCIPLES: In Switzerland, more and more patients go directly to the emergency
      department, bypassing general practitioners. However, a mixture of non-urgent
      walk-in patients and acute emergencies in the same emergency department can
      inevitably make it more difficult to provide genuine emergencies with rapid
      treatment, leading to deterioration in the quality of emergency services, and
      tending to increase on-floor mortality and morbidity, together with higher
      overall costs. METHODS: A series of 200 consecutive walk-in patients were
      interviewed during general practitioners' office hours. To avoid selection bias,
      we performed the survey on 31 randomly chosen days, between 11 July 2011 and 31
      August 2011, excepting weekends and Thursday afternoons, when GP offices in Bern
      are closed. The patients were interviewed using a paper based, self-administered
      questionnaire, which was distributed by a medical student not involved in the
      medical treatment. RESULTS: 200 patients were interviewed during the study
      period. The majority of walk-in patients interviewed (82%; n = 165) were
      registered with a GP. When asked about the circumstances of admission and
      subjective drivers to visit our emergency department, 39% (n = 61) patients
      reported greater confidence in the hospital emergency department. When asked if
      they saw a visit to a GP as appropriate, a majority stated that they preferred
      the hospital to their GP in any kind of emergency and the majority defined an
      emergency as either a condition requiring rapid attention or a life threatening
      situation (53%; n = 63). DISCUSSION: Our study is another small piece of the
      puzzle to help us to understand why people in "minor" medical emergencies prefer
      to consult a hospital than their own GP. Our study supported the evidence in
      current literature that there is a demand for hospital-based ambulatory emergency
      medicine. Only a future large study on the drivers and barriers to emergency care
      in Switzerland can provide additional answers.

PMID- 22653620
TI  - Nanoemulsion mucosal adjuvant uniquely activates cytokine production by nasal
      ciliated epithelium and induces dendritic cell trafficking.
AB  - While the nasal mucosa is a potentially useful site for human immunization, toxin
      based nasal adjuvants are generally unsafe and less effective in humans. Safe
      mucosal adjuvants that activate protective immunity via mucosal administration
      are highly dependent on barrier antigen sampling by epithelial and DCs. Here, we
      demonstrate that protein antigens formulated in unique oil-in-water nanoemulsions
      (NEs) result in distinctive transcellular antigen uptake in ciliated nasal
      epithelial cells, leading to delivery into nasal associated lymphoid tissue. NE
      formulation also enhances MHC class II expression in epithelial cells and DC
      activation/trafficking to regional lymphoid tissues in mice. These materials
      appear to induce local epithelial cell apoptosis and heterogeneous cytokine
      production by mucosal epithelial cells and mixed nasal tissues, including G-CSF,
      GM-CSF, IL-1a, IL-1b, IL-5, IL-6, IL-12, IP-10, KC, MIP-1a, TGF-beta, and TSLP.
      This is the first observation of a nasal adjuvant that activates calreticulin
      associated apoptosis of ciliated nasal epithelial cells to generate broad
      cytokine/chemokine responses in mucosal tissue.

PMID- 22653622
TI  - The WHO ILAR COPCORD Latin America: consistent with the world and setting a new
      perspective.

PMID- 22653623
TI  - Gout mimicking psoriatic arthritis flare.

PMID- 22653624
TI  - "Sandwich vertebrae" appearance in osteopetrosis.

PMID- 22653625
TI  - Gout, anemia, and hepatomegaly in a young man with glycogen storage disease.

PMID- 22653627
TI  - Herpes zoster in systemic lupus erythematosus.

PMID- 22653629
TI  - Policy and practice of work ability: a negotiation of responsibility in
      organizing return to work.
AB  - PURPOSE: In welfare policy and practical work it is unclear what the concept of
      work ability involves and assessments may be different among involved actors,
      partly due to a lack of theoretical research in relation to regulations and
      practice. Based on theoretical and legal aspects of work ability the aim of the
      study is to analyze stakeholders' perspectives on work ability in local practice
      by studying multi-stakeholder meetings. METHODS: The material comprises nine
      digitally recorded multi-stakeholder meetings. Apart from the sick-listed
      individual, representatives from the public Social Insurance Agency, health care,
      employers, public employment service and the union participated in the meeting.
      The material was analyzed using qualitative content analysis. RESULTS: Three
      perspectives on work ability were identified: a medical perspective, a workplace
      perspective and a regulatory perspective. The meetings developed into
      negotiations of responsibility concerning workplace adjustments, rehabilitation
      efforts and financial support. Medical assessments served as objective expert
      statements to legitimize stakeholders' perspectives on work ability and return to
      work. CONCLUSIONS: Although the formal goal of the status meeting was to
      facilitate stakeholder collaboration, the results demonstrates an unequal
      distribution of power among cooperating actors where the employers had the "trump
      card" due to their possibilities to offer workplace adjustments. The employer
      perspective often determined whether or not persons could return to work and if
      they had work ability.

PMID- 22653631
TI  - Diversity of endophytic fungal  community associated with Piper hispidum
      (Piperaceae) leaves.
AB  - Tropical  and subtropical plants are rich in endophytic community diversity.
      Endophytes,  mainly fungi and bacteria, inhabit the healthy plant tissues without
      causing  any damage to the hosts. These fungi can be useful for biological
      control of  pathogens and plant growth promotion. Some plants of the genus Piper
      are  hosts of endophytic microorganisms; however, there is little information
      about  endophytes on Piper hispidum, a medicinal shrub used as an insecticide, 
      astringent, diuretic, stimulant, liver treatment, and for stopping hemorrhages. 
      We isolated the fungal endophyte community associated with P. hispidum leaves 
      from plants in a Brazilian forest remnant. The endophytic diversity was  examined
      based on sequencing of the ITS1-5.8S-ITS2 region of rDNA. A high  colonization
      frequency was obtained, as expected for tropical angiosperms.  Isolated
      endophytes were divided into 66 morphogroups, demonstrating  considerable
      diversity. We identified 21 isolates, belonging to 11 genera (Alternaria,
      Bipolaris, Colletotrichum, Glomerella, Guignardia, Lasiodiplodia, Marasmius,
      Phlebia, Phoma, Phomopsis, and Schizophyllum);  one isolate was identified only
      to the order level (Diaporthales). Bipolaris was the most frequent genus among
      the identified endophytes. Phylogenetic  analysis confirmed the molecular
      identification of some isolates to genus level  while for others it was confirmed
      at the species level.

PMID- 22653630
TI  - Physical urticaria.
AB  - The physical urticarias are a heterogeneous subgroup of chronic urticarias in
      which wheals can be reproducibly induced by different specific physical stimuli
      such as cold, heat, pressure, vibration, or sunlight. Physical urticarias
      comprise up to 25 % of chronic urticarias and occur more frequently in young
      adults. Symptoms, i.e. wheal and flare responses or angioedema, are usually
      limited to the skin areas exposed to the eliciting stimulus. However, generalised
      urticaria with variable extracutaneous manifestations can also occur. Some
      patients may also present with more than one physical urticaria. Skin lesions in
      physical urticaria result from mast cell activation and mediator release. The
      mechanisms by which physical stimuli activate skin mast cells are not fully
      understood. Because of this, trigger avoidance and symptomatic treatment are key
      therapeutic concepts for physical urticarias. Identification of the inducing
      physical trigger, including its individual thresholds, is necessary for an
      effective therapy. Here, we have summarized clinical features, diagnostic workup
      and therapy options for physical urticarias.

PMID- 22653632
TI  - Optimization of DNA extraction from fresh leaf tissues  of Melanoxylon brauna
      (Fabaceae).
AB  - Melanoxylon brauna (Fabaceae - Caesalpinioideae) is an endemic and  valuable
      hardwood tree species in the Brazilian Atlantic rainforest; it is  comparable to
      African ebony wood. We tested three protocols of DNA extraction  based on the
      citrimonium bromide (CTAB) method and evaluated the quantity,  purity and
      integrity of the DNA. We also determined whether these procedures  interfere with
      PCR amplification in order to develop a protocol for M.  brauna. We found that
      the quality and integrity of DNA were improved with  the use of proteinase K in
      the extraction buffer and by modifications in the  centrifugation speed. The
      lowest concentration of DNA was obtained with Doyle  and Doyle's protocol (5.42
      ng/MUL). Ferreira and Grattapaglia's protocol modified for M.  brauna provided
      the most DNA (36.89 ng/MUL) and the highest quality DNA (purity ratio of 1.80 
      nm). The original Ferreira and Grattapaglia protocol provided 13.42 ng/MUL DNA;
      however, the purity ratio (1.44 nm)  indicates protein contamination. PCR results
      showed that Ferreira and  Grattapaglia's protocol modified for M. brauna gave
      satisfactory  quantity and purity of DNA for molecular studies.

PMID- 22653633
TI  - SLC30A8 (ZnT8) variations and  type 2 diabetes in the Chinese Han population.
AB  - In  recent genome-wide association studies, variants in the SLC30A8 gene have
      been  found to be associated with risk for type 2 diabetes. We examined a
      possible  association of tag SNPs spanning SLC30A8 and their haplotypes with type
      2 diabetes  in the Chinese Han population. There were 1508 Chinese Han type 2
      diabetes  patients and 1500 age- and gender-matched control subjects; all were
      genotyped  for three tagging SNPs (rs2466295, rs4876703, and rs11558471) of the
      human  SLC30A8 gene. The AA genotype of rs11558471 was found significantly more 
      frequently in type 2 diabetes patients than in controls (46 vs 24%). The 
      frequency of the A-C-A haplotype was significantly higher in type 2 diabetes 
      patients than in controls (0.331 vs 0.120). The frequency of the A-C-G  haplotype
      was significantly lower in type 2 diabetes patients than in controls  (0.160 vs
      0.365). We conclude that type 2 diabetes is associated with  the AA genotype of
      rs11558471 in the human SLC30A8 gene. The A-C-A haplotype  appears to be a risk
      factor and the A-C-G haplotype may be a protective factor  against type 2
      diabetes in Chinese Han.

PMID- 22653634
TI  - Impact of total hip arthroplasty on pain, walking ability, and cardiovascular
      fitness.
AB  - We tested the hypothesis that total hip arthroplasty (THA) patients have less
      pain and are able to walk longer post-operatively than pre-operatively, and that
      THA patients before and after have higher heart rates and compromised gas
      exchange determinants at rest and following exercise compared to healthy subjects
      with a post-operative improvement. Fifty-two patients completed questionnaires
      and an incremental walking stress test pre-operatively and 6-months after THA.
      Twenty-four age-matched control subjects completed the same stress test. Fifty
      one patients had less pain 6-months after THA compared to pre-operative levels.
      Forty-three patients showed an improvement of at least one walking duration
      category. Patients had compromised cardiovascular fitness compared to the control
      group with a tendency to improve after THA. Hence, 6-months following THA,
      deficits exist other than reduced strength as reported in the literature. Prior
      to THA, the ability to walk longer is compromised by pain and not by poor
      cardiovascular fitness. Studies on specific rehabilitation programs of varying
      intensities may demonstrate opportunities to improve the cardiovascular fitness
      of this population.

PMID- 22653635
TI  - Outpatient parenteral antibiotic therapy (OPAT) at home in Attica, Greece.
AB  - Outpatient parenteral antibiotic therapy (OPAT) is considered to be a cost
      effective and safe alternative treatment strategy to hospitalization. We
      retrospectively evaluated data regarding the demographic and treatment
      characteristics of patients that sought medical advice from a network of
      physicians performing house-call visits and who received OPAT at home during a 17
      month period (May 2009 to September 2010) in Attica, Greece. A total of 91
      patients (69.2 % females) received intravenous antibiotic therapy at home during
      the evaluated period. The mean age [+/- standard deviation (SD)] of the patients
      was 85.3 (+/- 9) years. The main indications were pneumonia [46 patients (50.5
      %)], urinary tract infection [25 (27.5 %)], and gastrointestinal tract infection
      [9 (9.9 %)]. Of the patients, 76.4 % received a beta-lactam, 17.5 % a
      fluoroquinolone, 15.3 % an imidazole, 8.7 % an aminoglycoside, and 5.4 % a
      lincosamide. The cure rate was 72.5 % and mortality was 27.5 %. The mean duration
      (+/- SD) of intravenous antibiotic treatment was 4.7 (+/- 3.3) days. The mean
      cost per patient was <euro>637 and was comparable to the mean cost if the patient
      were to be hospitalized for the same infection. There was significant clinical
      effectiveness of OPAT at home in this mainly elderly population, at an acceptable
      cost.

PMID- 22653636
TI  - Mosquito adulticidal activity of a biosurfactant produced by Bacillus subtilis
      subsp. subtilis.
AB  - BACKGROUND: A biosurfactant, surfactin, produced by a strain of Bacillus subtilis
      subsp. subtilis (VCRC B471), was effective in killing mosquito larval and pupal
      stages. As it was lethal to the non-feeding pupal stage, it was presumed that it
      could kill the adult mosquitoes also. In this study, the adulticidal effect of
      the biosurfactant was assessed in the laboratory against a malaria vector,
      Anopheles stephensi. RESULTS: The biosurfactant surfactin, separated from the
      culture supernatant of the production strain, showed mosquito adulticidal
      activity when tested as ultralow-volume (ULV) spray in a Peet-Grady chamber.
      Knockdown activity and mortality were found to increase with increasing surfactin
      dosage. Knockdown dosage (KD) and lethal dosage (LD) were calculated by
      statistical analysis. The KD(50) and KD(90) dosages were 10.73 and 26.39 mg m(-3)
      respectively. The LD(50) and LD(90) dosages were 16.13 and 39.21 mg m(-3) . The
      average droplet size of B. subtilis surfactin was 17.5 +/- 1.07 um. CONCLUSION:
      The present study indicates that the biosurfactant surfactin, produced by B.
      subtilis subsp. subtilis (VCRC B471), is a potential bioadulticide for ULV spray
      against malaria-transmitting Anopheles stephensi mosquitoes. This is the first
      report of a mosquito adulticide from a microbial source.

PMID- 22653637
TI  - Molecular dynamics simulation of thionated hen egg white lysozyme.
AB  - Understanding of the driving forces of protein folding is a complex challenge
      because different types of interactions play a varying role. To investigate the
      role of hydrogen bonding involving the backbone, the effect of thio substitutions
      in a protein, hen egg white lysozyme (HEWL), was investigated through molecular
      dynamics simulations of native as well as partly (only residues in loops) and
      fully thionated HEWL using the GROMOS 54A7 force field. The results of the three
      simulations show that the structural properties of fully thionated HEWL clearly
      differ from those of the native protein, while for partly thionated HEWL they
      only changed slightly compared with native HEWL. The analysis of the torsional
      angle distributions and hydrogen bonds in the backbone suggests that the alpha
      helical segments of native HEWL tend to show a propensity to convert to 3(10)
      helical geometry in fully thionated HEWL. A comparison of the simulated
      quantities with experimental NMR data such as nuclear overhauser effect (NOE)
      atom-atom distance bounds and (3)J((H)(N)(H)(alpha))-couplings measured for
      native HEWL illustrates that the information content of these quantities with
      respect to the structural changes induced by thionation of the protein backbone
      is rather limited.

PMID- 22653638
TI  - Anti-IL-6 receptor mAb eliminates myeloid-derived suppressor cells and inhibits
      tumor growth by enhancing T-cell responses.
AB  - CD11b(+) Gr-1(+) immature myeloid cells (ImCs), which are abnormally increased in
      tumor-bearing mice, were classified into three different subsets according to
      their phenotypic and morphological characteristics: Gr-1(low) F4/80(+)
      macrophages (MPhi-ImCs), Gr-1(mid) stab neutrophils (Neut(stab)-ImCs), and Gr
      1(high) segmented neutrophils (Neut(seg)-ImCs). In the spleen, only MPhi-ImCs but
      not Neut(stab)-ImCs and Neut(seg)-ImCs exhibited a significant immunosuppressive
      activity in MLR. In contrast, tumor-infiltrating leukocytes (TILs) contained only
      two ImC subsets, MPhi-ImCs and Neut(seg)-ImC, both of which exhibited stronger
      inhibitory activity against T cells compared with spleen-MPhi-ImCs. Thus, we
      concluded that tumor-infiltrating MPhi-ImCs and Neut(seg)-ImCs were fully
      differentiated myeloid-derived suppressor cells (MDSCs) with stronger T-cell
      inhibitory activity. Indeed, spleen MPhi-ImCs were converted into stronger MPhi
      MDSCs by tumor-derived factor (TDF). Moreover, both spleen Neut(stab)-ImCs and
      Neut(seg)-ImCs differentiated into Neut(seg)-MDSCs with suppressive activity
      after culture with TDF. We first demonstrated that administration of anti-IL-6R
      mAb could downregulate the accumulation of MPhi-MDSCs and Neut(seg)-MDSCs in
      tumor-bearing mice. The elimination of those MDSCs caused subsequent enhancement
      of antitumor T-cell responses, including IFN-gamma-production. The therapeutic
      effect of anti-IL-6R mAb was further enhanced by combination with gemcitabine
      (GEM). Thus, we propose that anti-IL-6R mAb could become a novel tool for the
      downmodulation of MDSCs to enhance antitumor T-cell responses in tumor-bearing
      hosts.

PMID- 22653639
TI  - Continuous EEG monitoring in the intensive care unit.
AB  - In the past 15 years, the increased availability and use of continuous
      electroencephalography (cEEG) in critically ill patients has substantially
      changed our understanding of the injured brain. We have become increasingly aware
      that electrographic seizures in this population may have only subtle or no
      clinical signs and that cEEG greatly increases the likelihood of detecting these
      seizures. This review highlights the rationale behind using cEEG rather than
      routine EEG for detection of nonconvulsive seizures and nonconvulsive status
      epilepticus in critically ill patients and defines which patients are at greatest
      risk. It also describes other applications of cEEG in the intensive care unit and
      how it may play an important role in monitoring brain function.

PMID- 22653640
TI  - Cardiac pre-competiton screening in Swiss athletes. Current situation in
      competitive athletes and short-time assessment of an exemplary local screening
      program.
AB  - AIM OF THE STUDY: In Switzerland, screening concepts for the prevention of sports
      associated sudden cardiac death are still insufficiently established in the large
      group of competitive athletes who are not integrated in an Olympic- or other high
      level squad. The aim of the present study was to objectively determine the
      current situation in this particular group of athletes concerning cardiac pre
      competition screening and define specific features of an "ideal" Swiss screening
      concept. Based on these data, the feasibility and validity was tested by the
      implementation of an exemplary local screening programme. METHODS: A standardised
      questionnaire was completed by 1,047 competitive athletes of different ages and
      gender. The individual, sports-specific profile of an athlete and furthermore,
      the personal attitude towards and the vision of a "perfect" cardiac screening
      were assessed. Based on the results, an exemplary local screening programme for
      competitive athletes was implemented at the "Academic Sports Association Zurich"
      (ASVZ) in Zurich, Switzerland and evaluated 1 year after its introduction.
      RESULTS: Only 9% of the 1,047 interviewed competitive athletes (aged 13 to 64
      years; median age 22 years, SD = 5.87) had previously undergone a cardiac
      screening. Only 47% of the interviewed competitive athletes expressed their
      interest to undergo a cardiac screening at all. Male and older athletes showed a
      significantly higher acceptance rate for the screening programme than women and
      younger athletes. All athletes accepted to bear the expenses for the baseline
      screening programme, adapted to international standards (minimal accepted fee of
      60 Swiss Francs). Almost half of the athletes (49.2%) preferred easy
      accessibility to a sports cardiologist (max. distance of 10 kilometres). The
      exemplary local screening programme proved to be feasible and successful.
      However, only 30% of the 102 screened individuals were female and most of the
      athletes (80%) who made use of the screening had a specific concern or symptom
      (selection bias). A total of 5 athletes (4.9%) were, at least temporarily,
      declared as not eligible for competitive sports due to a relevant cardiac
      pathology. CONCLUSION: The fact that only 9% of the interviewed competitive
      athletes had previously undergone cardiac screening is alarming, but underlines
      the necessity and urgency of implementing a cost-effective and adequate screening
      concept in the enormous group of competitive athletes who are not integrated in
      an Olympic- or other high-level squad. The need for a certain self-determination
      and personal responsibility of the athletes should be respected. Therefore, the
      screening should not be mandatory. However, adequate information about the issue
      is crucial for an informed decision.

PMID- 22653641
TI  - Insight into gene evolution within Cervidae and  Bovidae through genetic
      variation in MHC-DQA in the black muntjac (Muntiacus  crinifrons).
AB  - The critical role that the major histocompatibility  complex plays in the immune
      recognition of parasites and pathogens makes its  evolutionary dynamics
      exceptionally relevant to ecology, population biology,  and conservation studies.
      The black muntjac is a rare deer endemic to a small  mountainous region in
      eastern China. We found that this species has two DQA loci  through cDNA
      expression and sequence variation analysis. The level of variation  at both DQA
      loci was found to be extremely low (three alleles for DQA1 and four alleles for
      DQA2), possibly because of past bottlenecks and  the species' relatively solitary
      behavior pattern. The ratio of d(N)/d(S) in the putative peptide binding region
      of  the DQA2 locus (13.36, P = 0.012) was significantly larger than one but  not
      that of DQA1 (0.94, P = 0.95), suggesting strong positive selection  at the DQA2
      but not at the DQA1 locus. This difference might  reflect different sets of
      evolutionary selection pressures acting on the two  loci. The phylogenetic tree
      showed that DQA1 alleles from two species of  Cervidae and two of Bovidae grouped
      together, as did the DQA2 alleles.  However, different genes from the four
      species were located in separate  branches. These results lead us to suggest that
      these DQA alleles are  derived from primordial DQA genes from a common ancestor
      and are  maintained in Cervidae and Bovidae since their divergence around 25.5
      27.8  million years ago.

PMID- 22653642
TI  - Novel nonsense and frameshift NTRK1 gene  mutations in Chinese patients with
      congenital insensitivity to pain with  anhidrosis.
AB  - Congenital  insensitivity to pain with anhidrosis (CIPA; MIM 256800) is a rare
      autosomal  recessive disorder characterized by absence of reaction to noxious
      stimuli,  recurrent episodes of fever, anhidrosis, and mental retardation. It is
      caused  by mutations in the gene coding for neurotrophic tyrosine kinase receptor
      type  1 (NTRK1; MIM# 191315). We screened two Chinese CIPA cases for mutations 
      in the NTRK1 gene and examined their phenotype. Two novel mutations of  the NTRK1
      gene and two known mutations were identified. Including our  two novel mutations,
      there are now 62 different NTRK1 gene mutations  reported in patients with CIPA.
      We find that a combination of two null alleles  usually leads to the severe
      phenotype, while the mild form of the CIPA disease  is associated with at least
      one mild allele. Thirty-four among the 62 mutations  (55%) are located within the
      tyrosine kinase domain of the NTRK1 protein. We concluded  that the tyrosine
      kinase domain is a hot spot for mutations.

PMID- 22653643
TI  - Microarray-based gene  expression profiles in rabbit retina due to negative
      pressure suction.
AB  - We investigated a possible molecular pathogenesis  involving retinal ganglion
      cell apoptosis following transient high intraocular  pressure. Changes in the
      gene expression profiles of the retina were detected  via gene chip methodology.
      Twelve New Zealand white rabbits were randomly  assigned to control and 3-min
      negative pressure suction groups. The control  group was treated only with a
      laser, and the experimental group was also  treated with suction for 3 min, using
      a negative pressure generator. Total RNA  was then extracted from the retinal
      tissue at different recovery stages to  analyze gene expression profiles using
      the Agilent rabbit one-way gene chip.  The groups were then compared. Immediately
      after negative pressure suction  induction, 704 genes were differentially
      expressed. Among these, 485 genes were  upregulated, and 219 were downregulated.
      Expression of the genes encoding  CRYAA, CRYAB, and TLR3 genes, which are
      involved in apoptosis, was elevated. The  KRT18 gene, which is involved in
      apoptosis, had reduced expression. Seven days  after negative pressure suction,
      482 genes were differentially expressed. Among  these, 178 genes were
      upregulated, and 304 were downregulated. Expression of  the genes encoding CRYAB,
      IL1-BETA and IL1R1, which are involved in apoptosis,  was upregulated. Ten days
      after negative pressure suction, 402 genes were  differentially expressed. Of
      these, 213 genes were upregulated, and 189 were  downregulated. Apoptosis genes
      CRYAB, CRYBA3, CRYBB2, IL1- BETA, and IL1R1  showed higher expression levels. We
      concluded that negative pressure suction  for long periods of time (for example,
      3 min) results in changes in gene  expression. Genes with higher fold changes
      help protect retinal ganglion cells  from apoptosis. We suggest that promoting
      the expression of these genes should  be considered as a new means for treating
      ischemic-hypoxic retinopathy.

PMID- 22653644
TI  - Fine-scale spatial genetic  structure of an endangered marsh herb, Caldesia
      grandis (Alismataceae).
AB  - The  endangered marsh herb, Caldesia grandis, is native to China. We 
      investigated the spatial structure of the genetic variation of three  populations
      of C. grandis using RAPD markers and spatial  autocorrelation analysis, based on
      the method of equal distance interval. A  total of 157 individuals were sampled
      from four patches collected from the  region of Hunan and Yunnan Provinces,
      China. Among the polymorphic bands  generated by seven selective primers,
      polymorphic bands with frequencies  ranging from 20 to 80% were used to calculate
      Moran's I spatial  autocorrelation coefficient for each patch. We found
      significant spatial  structure of genetic variation in the three patches in Bei
      Hai (BH) (patches  BH-1 and BH-2) and Guai Hu (GH) (patch GH-1) populations of C.
      grandis (with significant positive autocorrelation within the short distance 
      class). In contrast, the genetic variation in the Lang Pan Hu (LPH) population 
      (patch LPH-1) was found to be randomly distributed. The different spatial 
      distribution patterns may be attributed to environment differences. These 
      results have implications for the conservation and management of this species, 
      especially for sampling strategies for ex situ conservation.

PMID- 22653645
TI  - Genetic instability and CpG methylation in the 5'-flanking region of the PAI-1
      gene in  Chinese patients with gastric cancer.
AB  - We explored a possible correlation of genetic  instability and CpG methylation in
      the 5'-flanking region of the PAI-1 gene  with clinicopathologic features of
      gastric cancer in Chinese patients and  looked for molecular markers for
      diagnosing gastric tumor development.  Microsatellite instability and loss of
      heterozygosity of the PAI-1 gene locus D7S515, D7S471 and pai-1 in 50 specimens
      of gastric cancer and relevant  pericancerous tissues were detected by PCR-single
      strand conformation  polymorphism (PCR-SSCP) with sliver staining. Methylation
      specific PCR was used  to detect CpG methylation in the 5'-flanking region of the
      PAI-1 gene.  Microsatellite instability was significantly more common in the
      negative than  in the positive serosa infiltration group of gastric cancer (42.86
      vs 2.33%).  The frequency of microsatellite instability was significantly lower
      in the  cases with lymph node metastasis than in those without metastasis (18.18
      vs 2.56%);  however, it was significantly higher in the low differentiation group
      than that  in the middle or high differentiation groups (21.05 vs 0.00%). CpG 
      methylation in the 5'-flanking region of the PAI-1 gene did not differ 
      significantly. Microsatellite instability and loss of heterozygosity of the  PAI
      1 gene apparently regulates the development of gastric cancer through  different
      pathways. Microsatellite instability could be used as a molecular  marker for the
      development of gastric cancer. CpG methylation in the  5'-flanking region of the
      PAI-1 gene appears not to be involved in the  development of gastric cancer.

PMID- 22653646
TI  - Increased expression of a  novel splice variant of the complement component 4
      (C4A) gene in  mastitis-infected dairy cattle.
AB  - The  complement system helps in the direct lysis of invading pathogens and
      modulates  phagocytic, humoral and cellular immune responses. Complement 4 is a
      critical  component in complement activity and protection against many bacterial 
      pathogens because it is essential to classical and lectin activation pathways. 
      We used reverse transcription and PCR to investigate alternative splicing and 
      expression of the complement component 4 (C4A) gene in Chinese Holstein  cattle.
      The PCR products were cloned and sequenced. A novel splice variant  involving
      intron 10 was identified, which we named C4A-AS. To examine how C4A gene activity
      is affected by bovine mastitis, six Chinese Holstein cattle  were divided into
      healthy (non-mastitic) and Staphylococcus aureus-induced  mastitic groups. Real
      time quantitative PCR (qRT-PCR) revealed that the  C4A-complete and C4A-AS
      transcripts are expressed at significantly different  levels in healthy cows,
      while there were no significant differences in the  mastitic group (P = 0.257).
      Expression of C4A-AS increased significantly when  mastitis developed. We also
      examined the expression of C4A-complete and C4A-AS  in several tissues (liver,
      heart, spleen, lung, kidney, tongue, and muscle).  The two transcripts were
      expressed in all of these tissues but there were no  significant differences in
      expression between healthy and mastitic cows. We  therefore conclude that the C4A
      complete transcript is the main transcript  under normal physiological
      conditions, while C4A-AS is augmented when mastitis  develops.

PMID- 22653647
TI  - Association between PPARgamma2 Pro12Ala  polymorphism and myocardial infarction
      and obesity in  Han Chinese in Hohhot, China.
AB  - Activation of the peroxisome proliferator-activated  receptor g (PPARg) improves
      insulin sensitivity and inhibits atherosclerosis.  Whether PPARg2 Pro12Ala
      polymorphism affects myocardial infarction is not  clearly understood. We
      investigated a possible association of PPARg2 Pro12Ala  polymorphism with obesity
      and myocardial infarction in Han Chinese in Hohhot,  Inner Mongolia, China. We
      included 121 subjects with myocardial infarction and  137 healthy controls in our
      study. Triglycerides, total cholesterol,  low-density lipoprotein cholesterol,
      and high-density lipoprotein cholesterol  were measured. The following
      information was recorded for each subject: age,  gender, body height, body
      weight, systolic blood pressure, and diastolic blood  pressure; the body mass
      index was calculated. PCR-RFLP was used to examine  Pro12Ala polymorphism. There
      were significant differences in clinical  characteristics between myocardial
      infarction patients and healthy controls,  except for diastolic blood pressure
      and triglycerides. The PP, PA/AA genotype  frequencies were 88.4 and 11.6% in
      myocardial infarction patients and 95.6 and  4.4% in controls, respectively (P =
      0.031). Individuals with the A allele had a  significantly higher risk of
      myocardial infarction. The A allele was not an  independent risk factor for
      obesity. We conclude that PPARg2 Pro12Ala  polymorphisms are associated with
      increased risk for myocardial infarction in  Han Chinese in Hohhot.

PMID- 22653648
TI  - SCAR markers for discriminating species of two genera  of medicinal plants,
      Liriope and Ophiopogon.
AB  - The development of DNA markers that can closely  discriminate between Liriope and
      Ophiopogon species is vital for  efficient and accurate identification of these
      species, and to ensure the  quality, safety, and efficacy of medicines made from
      these plants. We developed  species-specific molecular markers for these two
      genera. Forty RAPD primers  were tested to detect polymorphism; species-specific
      RAPD bands were  gel-purified, cloned, and sequenced. Primers for sequence
      characterized  amplified regions (SCARs) were then designed, based on nucleotide
      sequences of  specific RAPD primers. SCAR markers SA06 and SB05, specific to
      Ophiopogon  japonicus, amplified 460- and 553-bp DNA fragments, respectively. The
      marker SA12 amplified a 485-bp fragment specific to Liriope platyphylla.  This
      is the first report of a species-specific SCAR marker for this group.  These
      markers will be useful for rapid identification of closely related Liriope and
      Ophiopogon species.

PMID- 22653649
TI  - Molecular cloning, sequence characterization of a  novel pepper gene NADP-ICDH
      and its effect on cytoplasmic male sterility.
AB  - NADP-dependent isocitrate dehydrogenase (NADP-ICDH)  is an important enzyme
      involved in energy metabolism. The complete coding sequence  of the pepper
      (Capsicum annuum) NADP-ICDH gene was amplified  using a reverse transcriptase PCR
      based on the conserved sequence information  of the tomato and other Solanaceae
      plants and known highly homologous pepper  ESTs. Nucleotide sequence analysis
      revealed that the pepper NADP-ICDH gene  encodes a protein of 415 amino acids
      that has high homology with the proteins  of seven species, Solanum tuberosum
      (100%), Citrus limon (98%), Daucus  carota (98%), Nicotiana tabacum (98%), Vitis
      vinifera (99%), Arabidopsis  thaliana (97%), and Oryza sativa (98%). Tissue
      expression analysis  demonstrated that the pepper NADP-ICDH gene is over
      expressed in flower,  pericarp and seed, moderately in placenta, weakly in stem
      and leaf, hardly  expressed in root. At the abortion stages, activities and
      expression levels of NADP-ICDH in anthers of a sterile line were strongly
      reduced, while those in an F(1) hybrid remained  normal. Activities and
      expression levels of NADP-ICDH were too low to  maintain balanced energy
      metabolism in the sterile line, which indicated that  stable transcripts of NADP
      ICDH are necessary to maintain energy  metabolism at a normal level. When the
      restorer gene was transferred to the  cytoplasmic male sterile line, activities
      and expression level of NADP-ICDH were  regulated by the restorer gene and became
      stable. The restorer gene likely  plays an important role in keeping the balance
      of the energy metabolism within  normal levels during microspore development.

PMID- 22653650
TI  - Meta analysis of  angiotensin-converting enzyme I/D polymorphism as a risk factor
      for  preeclampsia in Chinese women.
AB  - Preeclampsia affects 3-8% of pregnancies and is a  major cause of maternal and
      perinatal morbidity and mortality worldwide.  Inappropriate activation of the
      renin-angiotensin system may play a role in the  development of preeclampsia. An
      insertion/deletion polymorphism in the  angiotensin-converting enzyme gene (ACE
      I/D) has been associated with  differences in ACE activity. However, there are
      controversies in reports on the  association of ACE-I/D with preeclampsia. Data
      were analyzed using Review  Manager Version 5.0 and a random effects model was
      applied irrespective of  between studies heterogeneity, which was evaluated via
      sensitivity and subgroup  analyses. Publication bias was evaluated using the fail
      safe number. A  systematic search was performed based on published case control
      studies up to  October 1, 2011, and 11 studies were included, involving 800
      patients and 949  controls. Significant association of the ACE D allele with
      increase risk  of preeclampsia was found (odds ratio = 1.93, 95% confidence
      interval =  1.19-3.12; P = 0.008). Sensitivity analysis showed that no individual
      study had  an undue influence on the summary odds ratios for all contrasts. An
      analysis  stratified by study size showed an attenuated odds ratio towards a null
      effect  as study size increased. Based on our meta-analysis, we suggest that the
      D  allele of the ACE gene is related with increased risk for preeclampsia  in the
      Chinese population. Considering the potential existence of small study  bias,
      further research should be performed with a larger dataset.

PMID- 22653651
TI  - Sex chromosome differentiation  in Belostoma (Insecta: Heteroptera:
      Belostomatidae).
AB  - Belostoma, a genus of the family Belostomatidae, includes species of great
      ecological importance as biocontrol agents. Few species of these species have
      been the subject of cytogenetic analyses. Karyotypic evolution in this genus
      involves agmatoploidy and simploidy; there are also different sex chromosome
      systems. We examined two Belostoma species (B. dilatatum and B. candidulum)
      collected from the Paranapanema River Basin (Brazil). Mitotic and meiotic
      analysis revealed 2n(?) = 26 + X1X2X3Y for B. dilatatum and 2n(?) = 14 + XY for
      B. candidulum; both karyotypes have holokinetic chromosomes. Differences in
      heterochromatin distribution were also observed between the species, besides
      variation in the localization of CMA3+/DAPI- blocks. The existence of different
      types of sex chromosome systems in these species was confirmed based on
      arrangements of the chromosomes in different meiotic stages. We identified a new
      sex system in B. dilatatum, and make the first cytogenetic report on B.
      candidulum.

PMID- 22653652
TI  - Forgiveness and health in christian women.
AB  - Researchers in psychology have studied the influence of forgiveness on the both
      the psychological and physical health of individuals. In addition, parish nursing
      is also looking at forgiveness as a potential benefit for self-care and health
      promotion. Forgiveness was measured using Enright's Forgiveness Inventory. Health
      was measured using Spielberg's State/Trait Anger measure, Beck's II Depression
      measure, SPF-15 Health Survey. Body Mass Index was also calculated. Mixed Methods
      was also used to describe the qualitative findings using content analysis on the
      types of unjust violations Christian women experienced. Women expressed very
      severe unjust violations involving sexual, physical, emotional, financial and
      spiritual abuse. Statistical correlations suggested important relationships among
      forgiveness and overall health measures warranting further investigation. The
      relationship between Church type and forgiveness raised questions about women's
      role in the Church as well as, the importance of acknowledging personal feelings,
      which are excluded in many orthodox denomination's doctrines. 

PMID- 22653653
TI  - Religion and disparities: considering the influences of Islam on the health of
      American Muslims.
AB  - Both theory and data suggest that religions shape the way individuals interpret
      and seek help for their illnesses. Yet, health disparities research has rarely
      examined the influence of a shared religion on the health of individuals from
      distinct minority communities. In this paper, we focus on Islam and American
      Muslims to outline the ways in which a shared religion may impact the health of a
      racially, ethnically, and socioeconomically diverse minority community. We use
      Kleinman's "cultural construction of clinical reality" as a theoretical framework
      to interpret the extant literature on American Muslim health. We then propose a
      research agenda that would extend current disparities research to include
      measures of religiosity, particularly among populations that share a minority
      religious affiliation. The research we propose would provide a fuller
      understanding of the relationships between religion and health among Muslim
      Americans and other minority communities and would thereby undergird efforts to
      reduce unwarranted health disparities. 

PMID- 22653655
TI  - Augmented autophagy pathways and MTOR modulation in fibroblasts from long-lived
      mutant mice.
AB  - Fibroblasts from long-lived pituitary dwarf mutants, including Snell dwarf, Ames
      dwarf and the growth hormone receptor knockout (GHRKO) mice, are resistant in
      culture to multiple forms of lethal stress. We found that fibroblasts from Snell
      dwarf and GHRKO mice are more susceptible than control cells to autophagy induced
      by amino acid withdrawal or by oxidative stress. We also found evidence for lower
      MTOR function in dwarf cells under conditions that induce autophagy, consistent
      with the evidence that increased autophagy requires lower TOR activity. Our
      results provide new hints about the connections between autophagy and aging in
      long-lived mutants with alterations in GH-IGF1 levels, and suggest a role for
      hyperactive autophagy in the resistance of cells from these mice to lethal
      stresses.

PMID- 22653656
TI  - Bioconversion of iodoacetophenones by marine fungi.
AB  - Nine marine fungi (Aspergillus sclerotiorum CBMAI 849, Aspergillus sydowii Ce19,
      Beauveria felina CBMAI 738, Mucor racemosus CBMAI 847, Penicillium citrinum CBMAI
      1186, Penicillium miczynskii Ce16, P. miczynskii Gc5, Penicillium oxalicum CBMAI
      1185, and Trichoderma sp. Gc1) catalyzed the asymmetric bioconversion of
      iodoacetophenones 1-3 to corresponding iodophenylethanols 6-8. All the marine
      fungi produced exclusively (S)-ortho-iodophenylethanol 6 and (S)-meta
      iodophenylethanol 7 in accordance to the Prelog rule. B. felina CBMAI 738, P.
      miczynskii Gc5, P. oxalicum CBMAI 1185, and Trichoderma sp. Gc1 produced (R)-para
      iodophenylethanol 8 as product anti-Prelog. The bioconversion of para
      iodoacetophenone 3 with whole cells of P. oxalicum CBMAI 1185 showed competitive
      reduction-oxidation reactions.

PMID- 22653654
TI  - Atherothrombotic disease, traditional risk factors, and 4-year mortality in a
      Latin American population: the REACH Registry.
AB  - BACKGROUND: Atherothrombosis is becoming the leading cause of chronic morbidity
      in developing countries. This epidemiological transition will represent an
      unbearable socioeconomic burden in the near future. We investigated factors
      associated with 4-year all-cause mortality in a Latin American population at high
      risk. HYPOTHESIS: Largely modifiable risk factors as well as polyvascular disease
      are the main predictors of 4-year all-cause and cardiovascular mortality in this
      Latin American cohort. METHODS: We analyzed 1816 Latin American stable
      outpatients (62.3% men, mean age 67 years) with symptomatic atherothrombosis
      (87.1%) or with multiple risk factors only (12.9%), in the Reduction of
      Atherothrombosis for Continued Health registry. RESULTS: Of patients with
      symptomatic atherothrombosis, 57.3% had coronary artery disease, 32%
      cerebrovascular disease, and 11.7% peripheral artery disease at baseline (9.1%
      polyvascular). The main risk factors were hypertension (76%),
      hypercholesterolemia (60%), and smoking (52.3%) in patients with established
      atherothrombosis; and hypertension (89.7%), diabetes (80.8%), and
      hypercholesterolemia (73.9%) in those with risk factors only. Four-year all-cause
      mortality steeply increased with none (6.8%), 1 (9.2%), 2 (15.5%), and 3 (29.2%)
      symptomatic arterial disease locations. In patients with only 1 location,
      cardiovascular mortality was significantly higher with peripheral artery disease
      (11.3%) than with cerebrovascular disease (6%) or coronary artery disease (5.1%).
      Significant baseline predictors of 4-year all-cause mortality were congestive
      heart failure (hazard ratio [HR]: 3.81), body mass index <20 (HR: 2.32),
      hypertension (HR: 1.84), polyvascular disease (HR: 1.69), and age >= 65 years
      (HR: 1.47), whereas statin use (HR: 0.49) and body mass index >= 30 (HR: 0.58)
      were associated with a reduced risk. CONCLUSIONS: Hypertension was the main
      modifiable risk factor for atherothrombosis and all-cause mortality in this Latin
      American cohort. Nearly one-third of the population with 3 symptomatic vascular
      disease locations died at 4-year follow-up.

PMID- 22653657
TI  - Immunomodulatory therapies delay disease progression in multiple sclerosis.
AB  - BACKGROUND: Few studies have analysed long-term effects of immunomodulatory
      disease modifying drugs (DMDs). OBJECTIVE: Assessment of the efficacy of DMDs on
      long-term evolution of multiple sclerosis, using a Bayesian approach to overcome
      methodological problems related to open-label studies. METHODS: MS patients from
      three different Italian multiple sclerosis centres were divided into subgroups
      according to the presence of treatment in their disease history before the
      endpoint, which was represented by secondary progression. Patients were
      stratified on the basis of the risk score BREMS (Bayesian risk estimate for
      multiple sclerosis), which is able to predict the unfavourable long-term
      evolution of MS at an early stage. RESULTS: We analysed data from 1178 patients
      with a relapsing form of multiple sclerosis at onset and at least 10 years of
      disease duration, treated (59%) or untreated with DMDs. The risk of secondary
      progression was significantly lower in patients treated with DMDs, regardless of
      the initial prognosis predicted by BREMS. CONCLUSIONS: DMDs significantly reduce
      the risk of multiple sclerosis progression both in patients with initial high
      risk and patients with initial low-risk. These findings reinforce the role of
      DMDs in modifying the natural course of the disease, suggesting that they have a
      positive effect not only on the inflammatory but also on the neurodegenerative
      process. The study also confirms the capability of the BREMS score to predict MS
      evolution.

PMID- 22653658
TI  - Dendritic cell, monocyte and T cell activation and response to glatiramer acetate
      in multiple sclerosis.
AB  - BACKGROUND: Treatment with glatiramer acetate (GA) modestly decreases disease
      activity in multiple sclerosis (MS). The mechanism of action is incompletely
      understood and differences in the response to treatment between individuals may
      exist. OBJECTIVE: To study the activation of CD4+ T cells, monocytes and
      dendritic cells (DC) in relation to disease activity in MS patients treated with
      GA. METHODS: Flow cytometry was used to study the activation of CD4+ T cells and
      T cell subsets (CD25(high) and CD26(high) cells), monocytes and DCs in a cross
      sectional study of 39 untreated and 29 GA-treated MS patients, the latter
      followed prospectively for one year. Gd-enhanced magnetic resonance imaging (MRI)
      studies were conducted in all patients. Disease activity was assessed as
      relapses. RESULTS: The median percentage of DCs expressing CD40 was 10% in
      untreated MS patients and 5.9% in GA-treated patients (Bonferroni-corrected
      p=0.0005). The hazard ratio of relapse was 1.32 (95% confidence interval 1.05
      1.64) per 1% increase in CD40+ DCs. Patients treated with GA had fewer CD4+ T
      cells expressing surface markers associated with T helper type 1 effector
      responses and more CD4+ T cells expressing surface markers associated with
      regulatory, naive or central memory T cell populations, but CD4+ T cell
      activation was not related with relapse risk. CONCLUSIONS: MS patients treated
      with GA show prominent changes in circulating antigen-presenting cells and CD4+ T
      cells. Expression of CD40 on DCs is significantly lower and associated with
      relapse risk in MS patients treated with GA.

PMID- 22653659
TI  - Long term benefit of multiple sclerosis treatment: an investigation using a novel
      data collection technique.
AB  - BACKGROUND: The Knowledge Program (KP) is an initiative to collect self-reported
      patient data and objective clinician assessments electronically at each
      outpatient clinical encounter. Available outcomes include the EuroQoL-5D (EQ5D),
      Patient Health Questionnaire-9 (PHQ9), Multiple Sclerosis Performance Scales
      (MSPS), and the timed 25-foot walk (T25FW). OBJECTIVE: This study was designed to
      use the KP to investigate the long-term benefits of early treatment (ET) in
      multiple sclerosis (MS). METHODS: The KP was queried for patients with relapsing
      remitting MS or secondary progressive MS who were >= 5 years from symptom onset.
      ET was defined as treatment with an approved agent for >= 3 of the first five
      years after symptom onset. Propensity scores for ET were calculated based on
      early clinical characteristics. Patients were divided into propensity score
      quintiles and linear regression models were constructed to determine the
      treatment effect sizes and confidence intervals. RESULTS: From the 1082 patients
      that met entry criteria, 453 patients (41.9%) received ET. Those patients
      receiving ET showed significantly better scores on the EQ5D index, PHQ9, and
      MSPS, but only in the upper three propensity quintiles. For the T25FW, ET did not
      result in significantly better times in any quintile. CONCLUSIONS: These results
      suggest that ET of MS is beneficial but the effect appears modest.

PMID- 22653661
TI  - Improved bioavailability of inhibitors of Trypanosoma cruzi trans-sialidase:
      PEGylation of lactose analogs with multiarm polyethyleneglycol.
AB  - The trans-sialidase of Trypanosoma cruzi (TcTS) catalyzes the transfer of sialic
      acid from host glycoconjugates to terminal beta-galactopyranosides in the mucins
      of the parasite. During infection, the enzyme is actively shed by the parasite to
      the bloodstream inducing hematological alterations. Lactitol prevents cell
      apoptosis caused by the TcTS, although it is rapidly eliminated from the
      circulatory system. Linear polyethyleneglycol (PEG) conjugates of lactose analogs
      were prepared but their clearance from blood was still quite fast. With the aim
      of improving their circulating half-lives in vivo, we now synthesized covalent
      conjugates of eight-arm PEG. The star-shape of these conjugates allows an
      increase in the molecular weight together with the loading of the active sugar.
      Two approaches were used for PEGylation of disaccharide derivatives containing
      beta-D-Galp as the non-reducing unit. (1) Amide formation between benzyl beta-D
      galactopyranosyl-(1->6)-2-amino-2-deoxy-alpha-D-glucopyranoside and a succinimide
      activated PEG. (2) Conjugation of lactobionolactone with amino end-functionalized
      PEG. Two 8-arm PEG derivatives (20 and 40 kDa) were used for each sugar.
      Substitution of all arms was proved by (1)H nuclear magnetic resonance (NMR)
      spectroscopy. The bioavailability of the conjugates in mice plasma was
      considerably improved with respect to the 5 kDa linear PEG conjugates retaining
      their inhibitory properties.

PMID- 22653662
TI  - The TF-antigen binding lectin from Sclerotium rolfsii inhibits growth of human
      colon cancer cells by inducing apoptosis in vitro and suppresses tumor growth in
      vivo.
AB  - Glycan array analysis of Sclerotium rolfsii lectin (SRL) revealed its exquisite
      binding specificity to the oncofetal Thomsen-Friedenreich (Galbeta1-3GalNAcalpha
      O-Ser/Thr, T or TF) antigen and its derivatives. This study shows that SRL
      strongly inhibits the growth of human colon cancer HT29 and DLD-1 cells by
      binding to cell surface glycans and induction of apoptosis through both the
      caspase-8 and -9 mediated signaling. SRL showed no or very weak binding to normal
      human colon tissues but strong binding to cancerous and metastatic tissues.
      Intratumor injection of SRL at subtoxic concentrations in NOD-SCID mice bearing
      HT29 xenografts resulted in total tumor regression in 9 days and no subsequent
      tumor recurrence. As the increased expression of TF-associated glycans is
      commonly seen in human cancers, SRL has the potential to be developed as a
      therapeutic agent for cancer.

PMID- 22653663
TI  - The conserved arginine 380 of Hsp90 is not a catalytic residue, but stabilizes
      the closed conformation required for ATP hydrolysis.
AB  - Hsp90, a dimeric ATP-dependent molecular chaperone, is required for the folding
      and activation of numerous essential substrate "client" proteins including
      nuclear receptors, cell cycle kinases, and telomerase. Fundamental to its
      mechanism is an ensemble of dramatically different conformational states that
      result from nucleotide binding and hydrolysis and distinct sets of interdomain
      interactions. Previous structural and biochemical work identified a conserved
      arginine residue (R380 in yeast) in the Hsp90 middle domain (MD) that is required
      for wild type hydrolysis activity in yeast, and hence proposed to be a catalytic
      residue. As part of our investigations on the origins of species-specific
      differences in Hsp90 conformational dynamics we probed the role of this MD
      arginine in bacterial, yeast, and human Hsp90s using a combination of structural
      and functional approaches. While the R380A mutation compromised ATPase activity
      in all three homologs, the impact on ATPase activity was both variable and much
      more modest (2-7 fold) than the mutation of an active site glutamate (40 fold)
      known to be required for hydrolysis. Single particle electron microscopy and
      small-angle X-ray scattering revealed that, for all Hsp90s, mutation of this
      arginine abrogated the ability to form the closed "ATP" conformational state in
      response to AMPPNP binding. Taken together with previous mutagenesis data
      exploring intra- and intermonomer interactions, these new data suggest that R380
      does not directly participate in the hydrolysis reaction as a catalytic residue,
      but instead acts as an ATP-sensor to stabilize an NTD-MD conformation required
      for efficient ATP hydrolysis.

PMID- 22653664
TI  - Classification of perimenstrual headache: clinical relevance.
AB  - Although more than 50% of women with migraine report an association between
      migraine and menstruation, menstruation has generally considered to be no more
      than one of a variety of different migraine triggers. In 2004, the second edition
      of the International Classification of Headache Disorders introduced specific
      diagnostic criteria for menstrual migraine. Results from research undertaken
      subsequently lend support to the clinical impression that menstrual migraine
      should be seen as a distinct clinical entity. This paper reviews the recent
      research and provides specific recommendations for consideration in future
      editions of the classification.

PMID- 22653665
TI  - Antigen amount dictates CD8+ T-cell exhaustion during chronic viral infection
      irrespective of the type of antigen presenting cell.
AB  - Chronic viral infections lead to CD8(+)  T-cell exhaustion, characterized by
      impaired cytokine secretion and loss of proliferative capacity. While viral load
      and T-cell dysfunction correlate, it is currently unclear whether the quality of
      a cell type presenting antigen determines the degree of T-cell exhaustion or if
      the overall amount of antigen recognized by T cells promotes exhaustion. We found
      that chronic lymphocytic chorio-meningitis virus infection led to decreased
      CD8(+)  T-cell exhaustion in DC-MHC class I (MHCI) mice, in which CD8(+)  T cells
      can only recognize antigen on DCs. However, this increase in CD8(+)  T-cell
      function came at the expense of fatal immunopathology. Additional antigen
      recognition on nonhematopoietic cells in DC-MHCI mice promoted T-cell exhaustion
      and avoidance of immunopathology. Likewise, increased numbers of antigen
      expressing hematopoietic cells, as well as a selective elevation of the number of
      DCs as the only cell type presenting antigen in DC-MHCI mice, resulted in
      compromised T-cell function. These results favor a scenario in which the overall
      amount of antigen exposure, rather than the type of cell engaging with virus
      specific CD8(+)  T cells, is responsible for their functional exhaustion.
      Furthermore, exhaustion of virus-specific CD8(+)  T cells leads to avoidance of
      life-threatening immunopathology.

PMID- 22653666
TI  - Influence of the pH on the synthesis of reduced graphene oxide under hydrothermal
      conditions.
AB  - Here we describe the important role played by the pH on the morphology and
      structure of the reduced graphite oxide (rGO) samples obtained by hydrothermal
      treatment of the previously prepared GO. The nature of the resulting samples has
      been studied on the basis of a complete battery of experimental techniques.

PMID- 22653667
TI  - Phosphatidylinositol 3-kinase inhibitor (PIK75) containing surface functionalized
      nanoemulsion for enhanced drug delivery, cytotoxicity and pro-apoptotic activity
      in ovarian cancer cells.
AB  - PURPOSE: Ovarian cancer is a debilitating disease, which needs multi-pronged
      approach of targeted drug delivery and enhanced efficacy with the use of
      combination therapeutics. In this study, we have examined the anticancer activity
      of PIK75 incorporated in surface functionalized nanoemulsions for targeted
      delivery to SKOV-3 cells. A pro-apoptotic molecule C(6)-ceramide was also co
      delivered to augment therapeutic efficacy. METHODS: EGFR and FR functionalized
      nanoemulsions incorporating PIK75 and C(6)-ceramide were characterized for
      particle size, surface charge, entrapment efficiency and morphology. Fluorescence
      and quantitative uptake studies were conducted in SKOV-3 cells to determine
      intracellular distribution. Cell viability was assessed using MTT assay while
      mechanism of cytotoxicity was evaluated using capsase-3/7, TUNEL and hROS assay.
      RESULTS: Cytotoxicity assay showed 57% decrease in IC(50) value of PIK75
      following treatment with EGFR targeted nanoemulsion and 40% decrease following
      treatment with FR targeted nanoemulsion. Combination therapy with PIK75 and
      ceramide enhanced the cytotoxicity of PIK75 compared to therapy with individual
      formulations. The increase in cytotoxicity was attributed to increase in cellular
      apoptosis and hROS activity. CONCLUSION: The results of this study showed that
      the targeted system improved cytotoxicity of PIK75 compared to the non-targeted
      system. Combination therapy with ceramide augmented PIK75's therapeutic activity.

PMID- 22653669
TI  - Molecular cytogenetic  identification of a wheat (Triticum aestivum)-American
      dune grass (Leymus  mollis) translocation line resistant to stripe rust.
AB  - Leymus  mollis, a perennial allotetraploid (2n = 4x = 28), known as American 
      dune grass, is a wild relative of wheat that could be useful for cultivar 
      improvement. Shannong0096, developed from interspecific hybridization between 
      common wheat cv. Yannong15 and L. mollis, was analyzed with cytological 
      procedures, genomic in situ hybridization, stripe-rust resistance  screening and
      molecular marker analysis. We found that Shannong0096 has 42  chromosomes in the
      root-tip cells at mitotic metaphase and 21 bivalents in the  pollen mother cells
      at meiotic metaphase I, demonstrating cytogenetic  stability. Genomic in situ
      hybridization probed with total genomic DNA  from L. mollis gave strong
      hybridization signals in the distal region of  two wheat chromosome arms. A
      single dominant Yr gene, derived from L.  mollis and temporarily designated as
      YrSn0096, was found on the long  arm of chromosome 4A of Shannong0096. YrSn0096
      should be a novel Yr gene  because none of the previously reported Yr genes on
      chromosome 4A are  related to L. mollis. This gene was found to be closely linked
      to the  loci Xbarc236 and Xksum134 with genetic distances of 5.0 and 4.8  cM,
      respectively. Based on data from 267 F(2) plants of  Yannong15/Huixianhong, the
      linkage map of YrSn0096, using the two  molecular markers, was established in the
      order Xbarc236-YrSn0096-Xksum134.  Shannong0096 appeared to be a unique wheat-L.
      mollis translocation with  cryptic alien introgression. Cytogenetic stability, a
      high level of stripe-rust  resistance, the common wheat background, and other
      positive agronomic traits  make it a desirable donor for introducing novel alien
      resistance genes in wheat  breeding programs, with the advantage of molecular
      markers that can be used to  confirm introgression.

PMID- 22653668
TI  - A family-based association study  identified CYP17 as a candidate gene for
      obesity susceptibility in Caucasians.
AB  - The  cytochrome P450c17alpha gene  (CYP17) encodes a key biosynthesis enzyme of
      estrogen, which is critical  in regulating adipogenesis and adipocyte development
      in humans. We therefore  hypothesized that CYP17 is a candidate gene for
      predicting obesity. In  order to test this hypothesis, we performed a family
      based association test to  investigate the relationship between the CYP17 gene
      and obesity  phenotypes in a large sample comprising 1873 subjects from 405
      Caucasian  nuclear families of European origin recruited by the Osteoporosis
      Research  Center of Creighton University, USA. Both single SNPs and haplotypes
      were  tested for associations with obesity-related phenotypes, including body
      mass  index (BMI) and fat mass. We identified three SNPs to be significantly 
      associated with BMI, including rs3740397, rs6163, and rs619824. We further 
      characterized the linkage disequilibrium structure for CYP17 and found  that the
      whole CYP17 gene was located in a single-linkage disequilibrium  block. This
      block was observed to be significantly associated with BMI. A major  haplotype in
      this block was significantly associated with both BMI and fat  mass. In
      conclusion, we suggest that the CYP17 gene has an effect on  obesity in the
      Caucasian population. Further independent studies will be needed  to confirm our
      findings.

PMID- 22653670
TI  - Differences in mitochondrial  gene expression profiles, enzyme activities and
      myosin heavy chain types in yak  versus bovine skeletal muscles.
AB  - Hypoxia  can affect energy metabolism. We examined gene expression and enzyme
      activity  related to mitochondrial energy metabolism, as well as myosin heavy
      chain (MyHC)  types in yaks (Bos grunniens) living at high altitudes. Real-time 
      quantitative PCR assays indicated that the yak has significantly lower levels  of
      carnitine palmitoyltransferase (CPT) mRNA in the biceps femoris and  lower levels
      of uncoupling protein 3 (UCP3) mRNA in both biceps femoris  and longissimus dorsi
      than in Yellow cattle. No significant differences between  yak and Yellow cattle
      were observed in the activities of mitochondrial beta-hydroxyacyl-CoA
      dehydrogenase,  isocitrate dehydrogenase and cytochrome oxidase in the same
      muscles.  Semi-quantitative RT-PCR analysis showed that the MyHC 1 mRNA levels in
      yak biceps femoris was lower than in Yellow cattle. We conclude that the yak 
      has significantly lower mRNA levels of CPT, UCP3, and MyHC 1 in  biceps femoris
      than in Yellow cattle, suggesting that the yak biceps femoris  has lower fatty
      acid oxidation capacity and greater glycolytic metabolic  potential.

PMID- 22653671
TI  - Isolation and characterization of new microsatellite  markers in the pen shell
      Atrina pectinata (Pinnidae).
AB  - The pen shell, Atrina pectinata, is a  commercially important bivalve species,
      widely consumed in the Asian Pacific  region. We identified 16 new microsatellite
      makers for A. pectinata using  a modified fast isolation by AFLP of sequences
      containing repeat protocols; 27  individuals were collected from Xiamen to
      evaluate the degree of polymorphism.  The number of polymorphic alleles per locus
      ranged from 2 to 11. The observed  and expected heterozygosities were 0.050-0.913
      and 0.049-0.869, respectively.  The loci identified in this study could provide a
      useful tool for research on  genetic diversity and genetic differentiation of A.
      pectinata populations.

PMID- 22653672
TI  - Identification of the e allele at the Extension  locus (MC1R) in Brazilian Creole
      sheep and its role in wool color  variation.
AB  - The melanocortin 1 receptor (MC1R) gene has been described as responsible for the
      black color in some breeds of sheep, but little is known about its function in
      many colored breeds, particularly those with a wide range of pigmentation
      phenotypes. The Brazilian Creole is a local breed of sheep from southern Brazil
      that has a wide variety of wool colors. We examined the MC1R gene (Extension
      locus) to search for the e allele and determine its role in controlling wool
      color variation in this breed. One hundred and twenty-five animals, covering the
      most common Creole sheep phenotypes (black, brown, dark gray, light gray, and
      white), were sequenced to detect the mutations p.M73K and p.D121N. Besides these
      two mutations, three other synonymous sites (429, 600, and 725) were found. The
      dominant allele (E(D): p.73K, and p.121N) was found only in colored animals,
      whereas the recessive allele (E+: p.73M, and p.121D) was homozygous only in white
      individuals. We concluded that MC1R is involved in the control of wool color in
      Brazilian Creole sheep, particularly the dark phenotypes, although a second gene
      may be involved in the expression of the white phenotype in this breed.

PMID- 22653673
TI  - Construction and preliminary  characterization of a river buffalo bacterial
      artificial  chromosome library.
AB  - River  buffalo genome analyses have advanced significantly in the last decade,
      and  the genome sequence of Bubalus bubalis will be available shortly. 
      Nonetheless, large-insert DNA library resources such as bacterial artificial 
      chromosomes (BAC) are still required for validation and accurate assembly of  the
      genome sequence. We constructed a river buffalo BAC library containing  52,224
      clones with an average insert size of 97 kb, representing 1.7 * coverage  of the
      genome. This genomic resource for river buffalo will facilitate further  studies
      in this economically important species allowing for instance, whole  genome
      physical mapping and isolation of genes and gene clusters, contributing  to the
      elucidation of gene organization and identification of regulatory  elements.

PMID- 22653674
TI  - Selection of peptides for  serological detection of equine infectious anemia.
AB  - Equine  infectious anemia caused by equine infectious anemia virus is an
      important  disease due to its high severity and incidence in animals. We used a
      phage  display library to isolate peptides that can be considered potential
      markers  for equine infectious anemia diagnosis. We selected peptides using IgG
      purified  from a pool comprised of 20 sera from animals naturally infected with
      equine  infectious anemia virus. The diagnostic potential of these peptides was 
      investigated by ELISA, Western blot and dot blot with purified IgG and serum 
      samples. Based on the results, we chose a peptide mimetic for glycoprotein gp45 
      epitopes of equine infectious anemia virus, with potential for use as an  antigen
      in indirect diagnostic assays. Synthesis of this peptide has possible 
      applications for the development of new diagnostic tools for this disease.

PMID- 22653675
TI  - Molecular diversity and  population structure of the forage grass Hemarthria
      compressa (Poaceae)  in south China based on SRAP markers.
AB  - Hemarthria  compressa is one of the most important and widely utilized  forage
      crops in south China, owing to its high forage yield and capability of 
      adaptation to hot and humid conditions. We examined the population structure  and
      genetic variation within and among 12 populations of H. compressa in  south China
      using sequence-related amplified polymorphism (SRAP) markers. High  genetic
      diversity was found in these samples [percentage polymorphic bands  (PPB) =
      82.21%, Shannon's diversity index (I) = 0.352]. However, there was  relatively
      low level of genetic diversity at the population level (PPB =  29.17%, I =
      0.155). A high degree of genetic differentiation among populations  was detected
      based on other measures and molecular markers (Nei's genetic  diversity analysis:
      G(ST) =  54.19%; AMOVA analysis: F(ST) =  53.35%). The SRAP markers were found to
      be more efficient than ISSR markers for  evaluating population diversity. Based
      on these findings, we propose changes in  sampling strategies for appraising and
      utilizing the genetic resources of this  species.

PMID- 22653676
TI  - Smoking is associated with impaired bone mass development in young adult men: a 5
      year longitudinal study.
AB  - It has previously been shown that smoking is associated with reduced bone mass
      and increased fracture risk, but no longitudinal studies have been published
      investigating altered smoking behavior at the time of bone mass acquisition. The
      aim of this study was to investigate the development of bone density and geometry
      according to alterations in smoking behavior in a 5-year, longitudinal,
      population-based study of 833 young men, age 18 to 20 years (baseline).
      Furthermore, we aimed to examine the cross-sectional, associations between
      current smoking and parameters of trabecular microarchitecture of the radius and
      tibia, using high-resolution peripheral quantitative computed tomography (HR
      pQCT), in young men aged 23 to 25 years (5-year follow-up). Men who had started
      to smoke since baseline had considerably smaller increases in areal bone mineral
      density (aBMD) at the total body (mean +/- SD, 0.020 +/- 0.047 mg/cm(2) versus
      0.043 +/- 0.040 mg/cm(2) , p < 0.01) and lumbar spine (0.027 +/- 0.062 mg/cm(2)
      versus 0.052 +/- 0.065 mg/cm(2) , p = 0.04), and substantially greater decreases
      in aBMD at the total hip (-0.055 +/- 0.058 mg/cm(2) versus -0.021 +/- 0.062
      mg/cm(2) , p < 0.01) and femoral neck (-0.077 +/- 0.059 mg/cm(2) versus -0.042 +/
      0.070 mg/cm(2) , p < 0.01) than men who were nonsmokers at both the baseline and
      follow-up visits. At the tibia, subjects who had started to smoke had a smaller
      increment of the cortical cross-sectional area (CSA) than nonsmokers (8.1 +/- 4.3
      mm(2) versus 11.5 +/- 8.9 mm(2) , p = 0.03), and a larger decrement of trabecular
      volumetric BMD (vBMD) than nonsmokers (-13.9 +/- 20.5 mg/mm(3) versus -4.1 +/-
      13.9 mg/mm(3) , p < 0.001). In the cross-sectional analysis at follow-up (23-25
      years of age), smokers had significantly lower trabecular vBMD at the tibia
      (7.0%, p < 0.01) due to reduced trabecular thickness (8.9%, p < 0.001), as
      assessed using HR-pQCT, than nonsmokers. In conclusion, this study is the first
      to report that men who start to smoke in young adulthood have poorer development
      of their aBMD at clinically important sites such as the spine and hip than
      nonsmokers, possibly due to augmented loss of trabecular density and impaired
      growth of cortical cross-sectional area.

PMID- 22653677
TI  - Quantification of islet size and architecture.
AB  - Human islets exhibit distinct islet architecture particularly in large islets
      that comprise of a relatively abundant fraction of alpha-cells intermingled with
      beta-cells, whereas mouse islets show largely similar architecture of a beta-cell
      core with alpha-cells in the periphery. In humans, islet architecture is islet
      size dependent. Changes in endocrine cell mass preferentially occurred in large
      islets as demonstrated in our recent study on pathological changes of the
      pancreas in patients with type 2 diabetes. ( 1) The size dependency of human
      islets in morphological changes prompted us to develop a method to capture the
      representative islet distribution in the whole pancreas section combined with a
      semi-automated analysis to quantify changes in islet architecture. The computer
      assisted quantification allows detailed examination of endocrine cell composition
      in individual islets and minimizes sampling bias. The standard
      immunohistochemistry based method is widely applicable to various specimens,
      which is particularly useful for large animal studies but is also applied to a
      large-scale analysis of the whole organ section from mice. In this article, we
      describe the method of image capture, parameters measured, data analysis and
      interpretation of the data.

PMID- 22653678
TI  - Prevalence of germline TP53 mutations and history of Li-Fraumeni syndrome in
      families with childhood adrenocortical tumors, choroid plexus tumors, and
      rhabdomyosarcoma: a population-based survey.
AB  - PURPOSE: Whether childhood adrenocortical tumors (ACTs), choroid plexus tumors
      (CPTs), and rhabdomyosarcoma (RMS) are early manifestation of Li-Fraumeni
      syndrome (LFS) is uncertain. In this study, we evaluated the frequency of
      germline TP53 mutations and family history in a population-based series of
      patients. PATIENTS AND METHODS: We identified children (<=18 years) diagnosed
      between 1958 and 2008 with ACT (n = 3) or CPT (n = 7), or children <=5 years with
      RMS (n = 29). Registry-based pedigree expansion was performed. RESULTS: No
      patients had a family history of classic LFS but 17 fulfilled Chompret or Eeles
      criteria. TP53 mutations were found in 1/3 ACT patients and 1/18 RMS patients;
      both were novel mutations. Of five tested CPT patients none had a detectable
      mutation. No excess of LFS associated tumors was observed, except for breast
      cancer in families of CPT patients. An overall increased cancer incidence was
      observed in families of patients with CPT [standardized incidence ratio (SIR) =
      2.0; 95% CI: 1.1-3.5] due to excess of breast and female kidney cancer and in
      families of patients with RMS (SIR = 1.2; 95% CI: 0.9-1.7), due to excess of
      early-onset melanoma and male stomach cancer. CONCLUSION: Relatives of patients
      with childhood ACTs, CPTs, and RMSs showed no increased risk of LFS associated
      tumors. However, TP53 mutations could be found in these children irrespective of
      family history. Absence of LFS associated tumors may suggest the presence of
      other cancer syndromes. Improved knowledge about relatives' cancer risks could be
      helpful in counseling family members of children with cancer.

PMID- 22653679
TI  - Abstracts of the ISPD 16th International Conference on Prenatal Diagnosis and
      Therapy. Miami, Florida, USA. June 3-6, 2012.

PMID- 22653680
TI  - Effort-reward and work-life imbalance, general stress and burnout among employees
      of a large public hospital in Switzerland.
AB  - INTRODUCTION: Effort-reward imbalance (ERI) and work-life imbalance (WLI) are
      recognised risk factors for work stress and burnout but have not been
      investigated conjointly so far and compared with each other in this regard. The
      present cross-sectional study provides initial evidence by studying associations
      of ERI and WLI with general stress and burnout simultaneously. METHODS: The study
      was based on survey data collected in 2007 among the personnel of a large public
      hospital in the canton of Zurich covering a random sample of 502 employees of all
      professions and positions. Prevalence rates, correlation coefficients,
      standardised regression coefficients and odds ratios were calculated as measures
      of association. RESULTS: Concerning the main research question and relating to
      the entire study sample, WLI was found to be more strongly associated with
      general stress and burnout than ERI. As stratified analyses with regard to
      burnout have shown, this applied especially to nursing, technical care and
      emergency staffs who account for more than three fifths of the study population.
      But for other professional categories like physicians, therapists and medical
      technical personnel the opposite of a stronger association of ERI with burnout
      was found. Results also suggested that general stress plays a (rather minor)
      mediating role in the relationships between ERI and burnout and particularly
      between WLI and burnout. CONCLUSION: For the prevention of chronic stress and
      burnout one should consider both high efforts put into work as well as all job
      demands that are competing and interfering with family responsibilities or other
      private activities should be considered.

PMID- 22653682
TI  - Biotechnological utilization of biodiesel-derived glycerol for the production of
      ribonucleotides and microbial biomass.
AB  - Ten yeast strains were evaluated concerning their capabilities to assimilate
      biodiesel-derived glycerol in batch cultivation. The influence of glycerol
      concentration, temperature, pH and yeast extract concentration on biomass
      production was studied for the yeast selected. Further, the effect of agitation
      on glycerol utilization by the yeast Hansenula anomala was also studied. The
      yeast H. anomala CCT 2648 showed the highest biomass yield (0.30 g g(-1)) and
      productivity (0.19 g L(-1) h(-1)). Citric acid, succinic acid, acetic acid and
      ethanol were found as the main metabolites produced. The increase of yeast
      extract concentration from 1 to 3 g L(-1) resulted in high biomass production.
      The highest biomass concentration (21 g L(-1)), yield (0.45 g g(-1)) and
      productivity (0.31 g L(-1) h(-1)), as well as ribonucleotide production (13.13 mg
      g(-1)), were observed at 700 rpm and 0.5 vvm. These results demonstrated that
      glycerol from biodiesel production process showed to be a feasible substrate for
      producing biomass and ribonucleotides by yeast species.

PMID- 22653681
TI  - Thermal stabilization of an endoglucanase by cyclization.
AB  - An intein-driven protein splicing approach allowed for the covalent linkage
      between the N- and C-termini of a polypeptide chain to create circular variants
      of the endo-beta-1,3-1,4-glucanase, LicA, from Bacillus licheniformis. Two
      circular variants, LicA-C1 and LicA-C2, which have connecting loops of 20 and 14
      amino acids, respectively, showed catalytic activities that are approximately two
      and three times higher, respectively, compared to that of the linear LicA (LicA
      L1). The thermal stability of the circular variants was significantly increased
      compared to the linear form. Whereas the linear glucanase lost half of its
      activity after 3 min at 65  degrees C, the two circular variants have 6-fold
      (LicA-C1) and 16-fold (LicA-C2) increased half-life time of inactivation. In
      agreement with this, fluorescence spectroscopy and differential scanning
      calorimetry studies revealed that circular enzymes undergo structural changes at
      higher temperatures compared to that of the linear form. The effect of calcium on
      the conformational stability and function of the circular LicAs was also
      investigated, and we observed that the presence of calcium ions results in
      increased thermal stability. The impact of the length of the designed loops on
      thermal stability of the circular proteins is discussed, and it is suggested that
      cyclization may be an efficient strategy for the increased stability of proteins.

PMID- 22653683
TI  - Antibodies and carbohydrate ligands binding to DC-SIGN differentially modulate
      receptor trafficking.
AB  - DCs are regarded as key APCs that initiate humoral and cellular immune responses.
      Consequently, targeted delivery of Ag toward DC-specific receptors enhances
      vaccine efficacy. DC-SIGN is a C-type lectin receptor that facilitates DC
      specific delivery of Ag. This is accomplished by conjugating Ag to receptor
      specific Ab or carbohydrate ligands that bind to its carbohydrate recognition
      domain. Here, we investigated the fate of DC-SIGN following receptor triggering
      with Ab. Both whole and single-chain Ab induced rapid internalization of about
      half of the surface receptor molecules. Biochemical studies showed that about
      half of the receptor molecules were still intracellular after 3 h, while minimal
      or no resurfacing of internalized or newly synthesized unbound DC-SIGN molecules
      was observed. Prolonged exposure of DCs to DC-SIGN Ab, but not carbohydrate
      ligands, resulted in reduced receptor expression levels, which lasted up to 2
      days following removal of the Ab. In addition, exposure to DC-SIGN Ab reduced the
      ability of the receptor to internalize. Consequently, DC-SIGN showed a poor
      ability to accumulate targeting Abs within DCs. Vaccine efficacy may therefore be
      enhanced by strategies increasing the amount of Ag entering via a single receptor
      molecule, such as the use of targeting moieties allowing DC-SIGN recycling or Ab
      coated vaccine carriers.

PMID- 22653684
TI  - The role of home smoking bans in limiting exposure to secondhand tobacco smoke in
      Hungary.
AB  - Our objective was to assess how exposure to secondhand tobacco smoke occurs in
      Hungarian homes, particularly among non-smokers, and to examine the effectiveness
      of home smoking bans in eliminating exposure to secondhand smoke at home. In
      2009, 2286 non-smokers and smokers aged 16-70 years, who were selected randomly
      from a nationally representative sample of 48 Hungarian settlements, completed
      paper-and-pencil self-administered questionnaires addressing tobacco-related
      attitudes, opinions and behaviors. Chi-square tests, one-way analysis of variance
      and multivariate logistic regression models were used to assess the effect of
      demographics, socio-economic characteristics and home smoking policies on the
      risk of exposure to secondhand tobacco smoke at home. Significantly higher risk
      of exposure was found among younger, lower educated and poorer people and among
      those having no or partial home smoking restrictions. There was a significant
      interaction between education level and home smoking policies: the effect of a
      smoking ban on exposure to secondhand tobacco smoke was stronger for the lower
      educated group than the higher educated group. The results suggest that
      Hungarians are making good progress in implementing home smoking bans, and that
      in the majority of population these bans are working. More can be done to promote
      the uptake of home smoking bans among poorer and less educated subpopulations.

PMID- 22653685
TI  - Prospective individual and social predictors of changes in adjustment for
      patients attending a regional cancer service.
AB  - PURPOSE: This study applied the social-cognitive processing (SCP) model to
      examine whether positive (social support) and negative (social constraints)
      aspects of the social environment influenced emotional distress, quality of life
      (QoL), well-being, and benefit finding after cancer. METHODS: Participants were
      439 adults at a median of 66 weeks post-diagnosis and 79 % of them had completed
      cancer treatments. Outcome measures and predictors were assessed twice, 6 months
      apart, and their relationships were analyzed using hierarchical multiple
      regressions. RESULTS: Participants reported improved physical QoL at retest.
      Correlations showed that better outcomes for depression, anxiety, QoL, and well
      being were associated with higher social support and lower social constraints. In
      addition, benefit finding correlated with social support but not social
      constraints. After other predictors were taken into account, lower initial social
      constraints were modestly associated with improved mental QoL at retest. Higher
      social constraints scores also predicted the development of clinically
      significant depression and anxiety. CONCLUSIONS: Results provided some support
      for the SCP model's prediction that both positive and negative aspects of social
      environment can contribute to adjustment in people with cancer. Although several
      findings supported the model, a heterogeneous sample and small effect sizes
      indicate that replication and further study is needed.

PMID- 22653686
TI  - Optimized noninvasive procedures to measure DNA damage in comet assay.
AB  - The comet assay is a well-established, simple and sensitive method to measure DNA
      damage in single cell and is commonly used in human trials to investigate the
      effects of pollution, occupational hazards and potential genoprotective agents.
      Peripheral blood lymphocytes are most commonly used in human biomonitoring
      studies, but lymphocytes collected from the mouth offer a potentially attractive,
      noninvasive alternative. The aim of the current study was to develop a buccal
      cell lymphocyte comet assay procedure. Cells were collected from mouthwash of
      three healthy volunteers and tested individually. The comet assay was performed
      under different pH and times of alkaline treatment, electrophoresis run times and
      hydrogen peroxide concentrations. Optimal conditions for buccal lymphocytes in
      comet assay were found to be pH >13 for unwinding and electrophoresis buffers, 10
      min alkaline unwinding treatment and 20-min electrophoresis run time. We
      successfully utilized our optimized assay conditions to demonstrate the
      genoprotective activity of quercetin. This newly established procedure offers an
      alternative noninvasive sampling method for the investigation of DNA protection
      and/or damaging effect.

PMID- 22653687
TI  - Effect of phenethyl isothiocyanate on Ca2+ movement and viability in MDCK canine
      renal tubular cells.
AB  - The effect of the natural compound phenethyl isothiocyanate (PEITC) on cytosolic
      Ca(2+) concentrations ([Ca(2+)](i)) and viability in MDCK renal cells is unknown.
      This study explored whether PEITC changed [Ca(2+)](i) in MDCK cells using the
      Ca(2+)-sensitive fluorescent dye fura-2. PEITC at 200-700 MUM increased
      [Ca(2+)](i) in a concentration-dependent manner. The signal was reduced by
      removing extracellular Ca(2+). PEITC-induced Ca(2+) influx was inhibited by
      nifedipine, econazole, SK&F 96365 and protein kinase C modulators. In Ca(2+)-free
      medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor
      thapsigargin (TG) or 2,5-di-tert-butylhydroquinone (BHQ) inhibited PEITC-induced
      rise in [Ca(2+)](i). Incubation with PEITC also inhibited TG or BHQ-induced rise
      in [Ca(2+)](i). Inhibition of phospholipase C with U73122 abolished PEITC-induced
      rise in [Ca(2+)](i). At 15-75 MUM, PEITC decreased viability. The cytotoxic
      effect of PEITC was enhanced by chelating cytosolic Ca(2+) with 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl ester. Annexin V
      FITC data suggest that 20 and 50 MUM PEITC induced apoptosis. At 10 and 15 MUM,
      PEITC did not increase reactive oxygen species (ROS) production. Together, in
      renal tubular cells, PEITC-induced rise in [Ca(2+)](i) by inducing phospholipase
      C-dependent Ca(2+) release from endoplasmic reticulum and Ca(2+) entry via store
      operated Ca(2+) channels. PEITC induced apoptosis in a concentration-dependent,
      ROS/Ca(2+)-independent manner.

PMID- 22653688
TI  - Can Atropa belladonna L. poisoning result in acute subdural hematoma?

PMID- 22653689
TI  - Effects of BQ-788 on amitriptyline-induced cardiovascular toxicity.
AB  - OBJECTIVE: We investigated both the effects of the endothelin type B (ETB)
      receptor antagonist, BQ-788, on amitriptyline-induced cardiotoxicity and the role
      of ETB receptors on amitriptyline-induced cardiovascular depression. METHODS:
      Male Wistar rats were anaesthetized with urethane/chloralose. Mean arterial
      pressure (MAP), heart rate (HR) and QRS duration were recorded. Toxicity was
      induced by amitriptyline infusion (0.94 mg/kg per min) until the 50% inhibition
      of MAP. In the first protocol, 5% dextrose or BQ-788 bolus was administered to
      control or experimental group animals, respectively. In the second protocol,
      after incubation with BQ-788 or 5% dextrose, amitriptyline was infused. RESULTS:
      Amitriptyline caused a significant decrease in MAP, prolonged QRS duration and
      decreased HR for both the groups. BQ-788 administration improved MAP (5, 10 and
      15 min), shortened the prolonged QRS (5 and 10 minutes) and increased HR (5, 10
      and 15 min) compared with dextrose group. While all the amitriptyline-infused
      rats survived in BQ-788 group, all the amitriptyline-infused rats died within 20
      min in dextrose group. In the second protocol, BQ-788 incubation did not cause
      any statistically significant change in amitriptyline-induced cardiovascular
      depression. CONCLUSION: BQ-788 may have beneficial effects in amitriptyline
      induced cardiovascular changes via a physiologic antagonism. ETB receptor
      antagonists may be the promising antidotes for the cardiovascular toxicity with
      hypotension and bradycardia.

PMID- 22653690
TI  - Determination of DNA damage after exposure to inhalation anesthetics in human
      peripheral lymphocytes and sperm cells in vitro by comet assay.
AB  - In this study, genotoxic activities of four halogenated anesthetics (halothane,
      isoflurane, sevoflurane and desflurane) were investigated in human peripheral
      blood lymphocytes (PBLs) and sperm cells in vitro by alkaline comet assay. For
      this purpose, sperm or lymphocyte suspension was exposed to different
      concentrations (0.1 mM, 1 mM, 10 mM and 100 mM) of anesthetic agents and 1%
      dimethyl sulfoxide (DMSO) or phosphate-buffered saline (PBS) as controls. The DNA
      strand breaks as well as alkali-labile sites were measured as percentage tail
      intensity with comet assay. The results of this study demonstrate that all
      analyzed drugs were capable of inducing DNA damage on PBLs in a dose-dependent
      manner in vitro. However, the results in sperm cells were slightly different
      since we did not observe any genotoxic effect for desflurane in any of the
      exposure doses, and the genotoxic effect of halothane was not dose dependent.
      This experimental study points out to the presence of DNA damage after exposure
      to halogenated anesthetics in both PBLs and sperm cells, although this effect
      seems to be higher in PBLs.

PMID- 22653691
TI  - Perindopril protects against streptozotocin-induced hyperglycemic myocardial
      damage/alterations.
AB  - High blood pressure, obesity, abnormal lipid profile, which often coexist with
      diabetes, tend to be associated with preclinical cardiovascular abnormalities and
      may contribute to the association of diabetes with cardiovascular events. Many
      studies have proved that streptozotocin (STZ) is responsible for type-2-diabetes
      induced cardiovascular complications. Long-term perindopril therapy in patients
      with hypertension and diabetes has been observed to correct carotid remodeling by
      reducing hypertrophy. We studied the effect of perindopril (1 mg/kg/d orally
      [po]) on cardiovascular complications in neonatal model of rats, which was
      induced by administering STZ (90 mg/kg, intraperitoneally [ip]), in 5-d-old
      wistar rats and cardiac hypertrophy induced by isoprenaline (ISO; 5 mg/kg, ip)
      for 10 d. Various biochemical, cardiac, and hemodynamic parameters were measured
      at the end of 8 weeks of treatment in diabetes model and 10 d in hypertrophy
      model. STZ produced hyperglycemia, hyperinsulinemia, dyslipidemia, hypertension,
      bradycardia, increased creatinine kinase (CK-MB), lactate dehydrogenase enzymes
      (LDH) and C-reactive protein (CRP) levels, cardiac hypertrophy, and oxidative
      stress. Chronic treatment with perindopril significantly prevented STZ-induced
      hyperglycemia and hyperinsulinemia and controlled dyslipdemia in diabetic rats.
      Further, perindopril produced a significant reduction in elevated levels of CRP,
      LDH, and CK. STZ-induced hypertension and bradycardia were also prevented by
      perindopril treatment. Perindopril also produced beneficial effect by preventing
      cardiac hypertrophy as evident from cardiac hypertrophy index and left
      ventricular hypertrophic index. Perindopril also prevented STZ-induced oxidative
      stress. Similar results were obtained in ISO-induced cardiac hypertrophic model,
      which confirms the beneficial role of perindopril in cardiac hypertrophy. In
      conclusion, our data from both studies suggest that perindopril produced
      beneficial effect on cardiac complications.

PMID- 22653692
TI  - Licorice induced hypokalemia, edema, and thrombocytopenia.
AB  - Licorice originates from the root of Glycyrrhiza glabra, which has a herbal
      ingredient, glycyrrhizic acid, and has a mineralocorticoid-like effect. Chronic
      intake of licorice induces a syndrome similar to that found in primary
      hyperaldosteronism. Excessive intake of licorice may cause a
      hypermineralocorticoidism-like syndrome characterized by sodium and water
      retention, hypertension, hypokalemia, metabolic alkalosis, low-renin activity,
      and hypoaldosteronism. In this case report, an association of hypokalemia, edema,
      and thrombocytopenia that is developed due to the excessive intake of licorice is
      presented. There are case reports in the literature, which suggest that toxicity
      findings may emerge with hyperaldosteronism-like manifestations such as
      hypokalemia, edema, and hypertension. However, any knowledge of thrombocytopenia
      as a resultant was not encountered among these reported toxic effects. Our case
      is important because it shows that the excessive intake of licorice may cause a
      toxic effect in the form of thrombocytopenia. This report is the first presented
      case to show thrombocytopenia due to licorice syrup consumption.

PMID- 22653694
TI  - The value of daily fetal heart rate home monitoring in addition to serial
      ultrasound examinations in pregnancies complicated by fetal gastroschisis.
AB  - OBJECTIVES: To audit the practice of daily fetal heart rate home monitoring (FHM)
      in pregnancies complicated by fetal gastroschisis (GS). METHODS: Prenatal records
      and pregnancy outcome were reviewed of all cases with fetal GS between 1999 and
      2010, managed with a consistent protocol, which included weekly fetal
      cardiotocography and ultrasound examinations after 30 weeks, and option of daily
      FHM. Data were collected including gestational age (GA) at FHM and the presence
      of fetal heart rate anomaly. Follow-up included fetal growth, amniotic fluid
      volume, gastrointestinal appearance and cardiotocography findings. RESULTS: One
      hundred five cases of GS were identified. Stillbirth rate was 1.9% (2/105). FHM
      was performed in 97/105 (92.4%) cases. Abnormal FHM was recorded in 24 cases.
      Fetuses with abnormal versus normal FHM were more likely to have C-section for
      fetal heart rate anomaly (50% vs 24%, p=0.025) at an earlier gestational age
      (34.9 +/- 1.7 vs 35.8 +/- 1.4 weeks, p=0.016). There was no difference in Apgar
      score or umbilical artery pH at birth. CONCLUSION: Fetal heart rate abnormalities
      are frequent in fetuses with GS. FHM appears useful in detecting fetal distress
      necessitating expedited delivery. However, the impact of a daily FHM policy on
      neonatal outcome should be evaluated in a randomized study.

PMID- 22653693
TI  - Catch up in bone acquisition in young adult men with late normal puberty.
AB  - The aim of this study was to investigate the development of bone mineral density
      (BMD) and bone mineral content (BMC) in relation to peak height velocity (PHV),
      and to investigate whether late normal puberty was associated with remaining low
      BMD and BMC in early adulthood in men. In total, 501 men (mean +/- SD, 18.9 +/-
      0.5 years of age at baseline) were included in this 5-year longitudinal study.
      Areal BMD (aBMD) and BMC, volumetric BMD (vBMD) and cortical bone size were
      measured using dual-energy X-ray absorptiometry (DXA) and pQCT. Detailed growth
      and weight charts were used to calculate age at PHV, an objective assessment of
      pubertal timing. Age at PHV was a strong positive predictor of the increase in
      aBMD and BMC of the total body (R(2) aBMD 11.7%; BMC 4.3%), radius (R(2) aBMD
      23.5%; BMC 22.3%), and lumbar spine (R(2) aBMD 11.9%; BMC 10.5%) between 19 and
      24 years (p < 0.001). Subjects were divided into three groups according to age at
      PHV (early, middle, and late). Men with late puberty gained markedly more in aBMD
      and BMC at the total body, radius, and lumbar spine, and lost less at the femoral
      neck (p < 0.001) than men with early puberty. At age 24 years, no significant
      differences in aBMD or BMC of the lumbar spine, femoral neck, or total body were
      observed, whereas a deficit of 4.2% in radius aBMD, but not in BMC, was seen for
      men with late versus early puberty (p < 0.001). pQCT measurements of the radius
      at follow-up demonstrated no significant differences in bone size, whereas
      cortical and trabecular vBMD were 0.7% (p < 0.001) and 4.8% (p < 0.05) lower in
      men with late versus early puberty. In conclusion, our results demonstrate that
      late puberty in males was associated with a substantial catch up in aBMD and BMC
      in young adulthood, leaving no deficits of the lumbar spine, femoral neck, or
      total body at age 24 years.

PMID- 22653695
TI  - Intracranial EEG surface renderings: new insights into normal and abnormal brain
      function.
AB  - Intracranial electro-encephalography (icEEG) provides a unique opportunity to
      record directly from the human brain and is clinically important for planning
      epilepsy surgery. However, traditional visual analysis of icEEG is often
      challenging. The typical simultaneous display of multiple electrode channels can
      prevent an in-depth understanding of the spatial-time course of brain activity.
      In recent decades, advances in the field of neuroimaging have provided powerful
      new tools for the analysis and display of signals in the brain. These methods can
      now be applied to icEEG to map electrical signal information onto a three
      dimensional rendering of a patient's cortex and graphically observe the changes
      in voltage over time. This approach provides rapid visualization of seizures and
      normal activity propagating over the brain surface and can also illustrate subtle
      changes that might be missed by traditional icEEG analysis. In addition, the
      direct mapping of signal information onto accurate anatomical structures can
      assist in the precise targeting of sites for epilepsy surgery and help correlate
      electrical activity with behavior. Bringing icEEG data into a standardized
      anatomical space will also enable neuroimaging methods of statistical analysis to
      be applied. As new technologies lead to a dramatic increase in the rate of data
      acquisition, these novel visualization and analysis techniques will play an
      important role in processing the valuable information obtained through icEEG.

PMID- 22653696
TI  - How the early voltage clamp studies of Jose del Castillo inform "modern"
      neuroscience.
AB  - The description of ionic currents that flow across the membrane of the squid
      giant axon during an action potential sparked an interest in determining whether
      there were similar currents in vertebrates. The preparation of choice was the
      node of Ranvier in single myelinated fibers in frog. Jose del Castillo spent 3
      years on the United States mainland from 1956 to 1959. During that time, he
      collaborated with Jerome Y. Lettvin and John W. Moore. I discuss how these
      individuals met one another and some of their scientific discoveries using the
      voltage clamp to study squid giant axons and frog nodes. Much of this work was
      conducted at the Marine Biological Laboratory in Woods Hole, MA, and I attempt to
      convey a sense of the unique scientific "melting pot" that existed at the Marine
      Biological Laboratory and the broader effect that del Castillo had on "modern"
      neuroscience.

PMID- 22653697
TI  - [The effect of oral calcium lactate in postpartum cows].
AB  - The oral administration of calcium lactate for prophylaxis of bovine parturient
      paresis has been promoted for a number of years. The goal of the present study
      was to investigate the effect of this treatment on the serum concentrations of
      calcium, inorganic phosphorus and magnesium in parturient cows. Five fresh calved
      cows were given a drench containing calcium lactate and 5 control cows received
      the same drench but without calcium lactate. There were no significant
      differences in the serum concentrations of total and ionised calcium and
      magnesium between treated and control cows within 24 hours of treatment. Because
      the calcium lactate drench did not significantly affect calcium concentrations in
      the blood of fresh cows, it appears highly questionable whether the
      administration of calcium lactate decreases the risk of bovine parturient
      paresis. Based on our results, the oral administration of calcium lactate can not
      be recommended for prophylaxis of bovine parturient paresis.

PMID- 22653698
TI  - Sepsis and bacterial suppurative meningitis-meningoencephalitis in critically ill
      neonatal Piedmontese calves: clinical approach and laboratory findings.
AB  - Sepsis (S) and bacterial suppurative meningitis-meningoencephalitis (M-ME) are
      common causes of death in bovine neonates. The aim of this prospective study was
      to evaluate the prevalence of S and M-ME in critically ill neonatal Piedmontese
      calves. Critically ill animals up to 15 days old referred by practitioners were
      registered according to their status and subsequently assigned to clinical
      standardized score. Calves with a clinical score > = 5 were further assessed
      under a clinical and clinical-pathological protocol to strengthen the suspicion
      of S and M-ME. Critically ill neonatal calves sent for necropsy were included in
      the study as well. Fifty-nine calves were investigated, 26 of which referred
      alive and 33 dead. Ten out of the 26 clinically evaluated calves were classified
      as suspicious of S on the basis of the clinical and clinical-pathological
      protocols. S was confirmed by positive bacteriologic culture in 7 cases and in 3
      cases on the basis of necroptic lesions. Concomitant suppurative M-ME suspected
      in 6 of these 10 calves was subsequently confirmed by CSF analysis or
      histological findings. Of the 33 calves examined only post-mortem, 20 showed
      pathognomonic findings of S and 14 signs of M-ME. The prevalence of S and M-ME
      was 46 and 36 %, respectively. Clinical signs of S were confirmed to be vague and
      overlapping with other diseases. The developed protocol was highly accurate in
      predicting S in these neonatal calves.

PMID- 22653699
TI  - Antimicrobial susceptibility of canine Clostridium perfringens strains from
      Switzerland.
AB  - Fifty Clostridium perfringens strains were isolated from individual dogs with
      acute diarrhoea that were not given antibiotics. Toxin types and minimal
      inhibitory concentrations of 15 antibiotics were determined for each of them. All
      strains harboured the alpha-toxin gene, 12 of them had both the alpha- and entero
      toxin gene and 5 had both the alpha- and beta2-toxin gene. Eighteen percent of
      the isolates showed resistance to tetracycline and 54 % showed decreased
      susceptibility to metronidazole which is one of the most frequently used
      antibiotics in the treatment of canine diarrhoea. Apart from that, all isolates
      were susceptible to the remaining antibiotics tested. These findings lead to the
      conclusion that despite a general susceptibility to antibiotics in C.
      perfringens, resistance is developing in isolates from dogs. Therefore, careful
      identification of the pathogenic agent and antibiotic susceptibility testing
      should be performed prior to therapy in order to minimise further selection of
      antibiotic resistance.

PMID- 22653700
TI  - [Incidence and genotypes of Toxoplasma gondii in the muscle of sheep, cattle,
      pigs as well as in cat feces in Switzerland].

PMID- 22653701
TI  - [e-TAK - The Swiss Veterinary Drug Compendium for smartphones and tablet
      computer].

PMID- 22653702
TI  - [TVS: effective, but also well known?].

PMID- 22653703
TI  - [Customer complaints - what you should know].

PMID- 22653704
TI  - A novel KIF11 mutation in a Turkish patient with microcephaly, lymphedema, and
      chorioretinal dysplasia from a consanguineous family.
AB  - Microcephaly-lymphedema-chorioretinal dysplasia (MLCRD) syndrome is a rare
      syndrome that was first described in 1992. Characteristic craniofacial features
      include severe microcephaly, upslanting palpebral fissures, prominent ears, a
      broad nose, and a long philtrum with a pointed chin. Recently, mutations in KIF11
      have been demonstrated to cause dominantly inherited MLCRD syndrome. Herein, we
      present a patient with MLCRD syndrome whose parents were first cousins. The
      parents are unaffected, and thus a recessive mode of inheritance for the disorder
      was considered likely. However, the propositus carries a novel, de novo nonsense
      mutation in exon 2 of KIF11. The patient also had midline cleft tongue which has
      not previously been described in this syndrome.

PMID- 22653705
TI  - Atopaxar and its effects on markers of platelet activation and inflammation:
      results from the LANCELOT CAD program.
AB  - Atopaxar is a reversible protease activated receptor (PAR)-1 thrombin receptor
      antagonist that interferes with platelet signaling. The effects of PAR-1
      antagonists on biomarkers remain unknown. The primary objective was to assess the
      effects of atopaxar on biomarkers of inflammation and platelet activation. The
      LANCELOT-CAD trial randomized 720 subjects to atopaxar (50, 100, or 200 mg daily)
      or matching placebo for 24 weeks. Biomarkers were assessed at serial time points.
      A linear mixed model to account for repeated measures was used to evaluate the
      change in biomarker concentration from randomization across time to week 24.
      Least square means were determined from the linear mixed models. The
      concentration of sCD40L decreased on average over time by -553 (95 % CI -677, 
      429) ng/L in the combined atopaxar group versus -30.3 (-249 to 189) ng/L fall in
      the placebo arm (P < 0.001) and a dose-dependent trend was seen across treatment
      groups (P < 0.001 for trend). In contrast, Lp-PLA(2) mass rose on average over
      time by 12.6 (95 % CI 10.0, 15.3) ng/ml in the combined atopaxar group as
      compared with 2.6 (95 % CI -2.1, 7.3) ng/ml in the placebo arm (P < 0.001).
      Similarly, the concentration of IL-18 rose by 17.5 (95 % CI 12.4, 22.6) pg/ml in
      the atopaxar group versus a -1.2 (95 % CI -10.2, 7.8) pg/ml fall in the placebo
      group (P < 0.001). The effects of atopaxar on Lp-PLA(2) and IL-18 appeared to be
      dose-dependent (P < 0.001 for trend) and were observed in J-LANCELOT. Atopaxar
      did not have a significant effect on other inflammatory markers. In conclusion,
      atopaxar appeared to decrease sCD40L, but did not demonstrate an anti
      inflammatory effect in patients with stable CAD. Although atopaxar increased the
      concentration of Lp-PLA(2) and IL-18, the clinical relevance of these findings
      remains unknown and warrants further investigation and validation.

PMID- 22653706
TI  - Thromboprophylaxis in major knee and hip replacement surgery: a review.
AB  - Patients undergoing total knee and total hip replacement (THR/TKR) surgery are at
      high risk of venous thromboembolism (VTE), and routine thromboprophylaxis is
      recommended after these procedures. However, current thromboprophylaxis may
      require daily injections, careful anticoagulation monitoring, and dietary
      restrictions, which can lead to poor patient compliance and suboptimal outcomes.
      Therefore, there is an unmet need for simpler medication options. Newer oral
      anticoagulants have improved efficacy over standard treatments, with convenient
      dosing regimens, more predictable pharmacologic profiles that reduce the need for
      anticoagulation monitoring, and fewer drug or food interactions. These drugs have
      the potential to simplify anticoagulation after THR or TKR surgery, which may
      lead to improved adherence, thus lowering the incidence of VTE and associated
      complications after surgery.

PMID- 22653707
TI  - AA amyloidosis: basic knowledge, unmet needs and future treatments.
AB  - Systemic AA amyloidosis is a long-term complication of several chronic
      inflammatory disorders, including rheumatoid arthritis, ankylosing spondylitis,
      autoinflammatory syndromes, Crohn's disease, malignancies and conditions
      predisposing to recurrent infections. Organ damage results from the extracellular
      deposition of proteolytic fragments of the acute-phase reactant serum amyloid A
      (SAA) as amyloid fibrils. A sustained high concentration of SAA is the
      prerequisite for developing AA amyloidosis. However, only a minority of patients
      with long-standing inflammation actually presents with this complication,
      pointing to the existence of disease-modifying factors, the best characterised of
      which being SAA1 genotype. The kidneys, liver and spleen are the main target
      organs of AA amyloid deposits. In more than 90% of patients proteinuria,
      nephrotic syndrome and/or renal dysfunction dominate the clinical picture at
      onset. If not effectively treated, this disease invariably leads to end stage
      kidney disease and renal replacement therapy, that are still associated with a
      poor outcome.  Although the incidence of AA in rheumatoid arthritis and other
      chronic arthritides has continuously decreased over the past ten years, thanks to
      the increasing availability of more effective anti-inflammatory and
      immunosuppressive therapies, AA remains a life-threatening disease with several
      areas of uncertainty and unmet needs, deserving continuous efforts at prevention
      and effective treatment. The deeper understanding of the molecular mechanisms of
      amyloid formation and regression is now driving the development of novel
      treatments targeting different steps in the amyloidogenic cascade. These
      therapies will hopefully improve the quality of life and outcome of these
      patients in a near future.

PMID- 22653708
TI  - Determination of distributions of Cd, Cu, and Pb concentrations in sediments of a
      Mexican reservoir to infer their environmental risk.
AB  - The Jose Antonio Alzate Dam in the State of Mexico, Mexico, receives wastewaters
      from domestic, industrial, and agricultural activities through the Lerma River.
      Chemical and physicochemical characteristics of the water were determined.
      Sediment has been studied in order to define the importance of its influence on
      the reservoir's state as a whole. The quantification of the metals, Cd, Cu, and
      Pb in total forms and the geochemical distribution and the chemical mobility of
      these metals in sediment have been established using a chemical sequential
      extraction scheme. The three metals showed a common characteristic, being more
      abundant in fraction F6 (residual), but the other fractions of the geochemical
      distribution were variable depending on the metal. First, the contamination level
      was evaluated with the results of the total metals, using the criteria of EPA,
      Thomas and Murdoch, and the Ontario Ministry of Environment for sediment in water
      bodies. Subsequently, the risk was assessed using the same criteria but
      considering the results of sequential extractions, where the geochemical
      distribution of each metal allowed a better understanding of metal portions with
      more influence on the risk, in which Cu and Pb presented low risk, but not Cd.

PMID- 22653710
TI  - Body stalk anomaly in Denmark during 20 years (1970-1989).
AB  - Body stalk anomaly is a severe defect of the abdominal wall with uncovered
      thoracic and/or abdominal organs. The umbilical cord is absent or very short.
      Here I present epidemiological and clinical data on 16 infants with body stalk
      anomaly. The 16 infants represent 3.4% of the 469 infants ascertained in an
      almost complete nationwide data set of live- and stillborn infants born with
      abdominal wall defects during the two decades 1970-1989 in Denmark. The
      prevalence was 0.12 per 10,000 live- and stillborn. Nine of the infants were
      stillbirths, seven were live births, and they all died shortly after birth. The
      gestational age at birth varied from 33 to 40 weeks. There was an excess of males
      M/F ratio: 2.2 (CI: 0.85-10.71). All infants had severe associated malformations.
      Among the most severe were: severe limb reduction defects (56%), absence of one
      kidney associated with malformations of genitalia and/or urinary bladder (62%),
      scoliosis (82%), and anal atresia (57%). A normal karyotype was found in all
      eight of the infants who were tested. There were two sets of twins; one
      discordant and one concordant. Mean maternal and paternal ages were 28.5 and 29.5
      years, respectively, not significantly different from the mean parental ages of
      the Danish population during the same period.

PMID- 22653712
TI  - Concise review: the role of hematopoietic stem cell transplantation in the
      treatment of acute myeloid leukemia.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially
      curative option for patients with acute myeloid leukemia (AML). Our understanding
      of the biology of leukemic stem cells has continued to improve over the last
      decade and risk stratification using cytogenetics and molecular markers have
      improved our ability to select patients who would benefit from allogeneic
      transplantation. Results of HSCT have also improved substantially, extending the
      potential application of allogeneic transplant to more patients. This review
      discusses the theoretical aspects of transplant, analyzes clinical results, and
      provides recommendations for the use of HSCT in AML. Further study of the biology
      of leukemic stem cells and the role for HSCT is necessary to optimize outcomes in
      AML patients.

PMID- 22653709
TI  - Rapid early innate control of hepatitis C virus during IFN-alpha treatment
      compromises adaptive CD4+ T-cell immunity.
AB  - The ability to control HCV with IFN-alpha-based treatments provides an
      opportunity in humans to study how the rate of viral clearance in vivo impinges
      on the development of antiviral responses. Ex vivo (IFN-gamma-producing) and
      cultured antiviral CD4(+)  T cells, serum cytokines, and viral loads were
      measured repeatedly in a cohort of chronically HCV-infected subjects (n = 33)
      receiving IFN-alpha. Rapid control of virus indicated by an increased calculated
      rate of virus clearance, occurred in those subjects demonstrating absent/minimal
      T-cell responses (p < 0.0006). Surprisingly, in subjects who demonstrated the
      most robust T-cell responses (and reduced serum IL-10), there was actually a
      reduced rate of early virus clearance. A subsequent analysis of NK-cell function
      in available subjects (n = 8) revealed an inverse correlation between
      pretreatment NK-cell expression of NKp46 and the potential to upregulate
      cytotoxic function on exposure to IFN-alpha (p < 0.004), as well as the
      subsequent measured rate of viral clearance (p = 0.045). Thus, the CD4(+)  T-cell
      response during IFN-alpha treatment appears to be shaped by the rate of innate
      virus suppression. These data suggest that individuals who respond most
      effectively to immune intervention may be most in need of subsequent vaccination
      to prevent reinfection.

PMID- 22653711
TI  - Reference ranges for time-related analysis of ductus venosus flow velocity
      waveforms in singleton pregnancies.
AB  - OBJECTIVES: To investigate time intervals of ductus venosus (DV) flow velocity
      waveforms (FVW) in correlation to fetal heart rate and gestational age and to
      construct reference ranges for the second and third trimester. Furthermore, we
      investigate time intervals of FVW through the tricuspid valve. METHODS: Flow
      velocity waveforms of the DV and through the tricuspid valve were recorded in 135
      normal singleton fetuses between 17 and 38 weeks' gestation. Time intervals for
      systolic (S) and early diastolic (D) peaks were analyzed regarding acceleration
      time (acc-S for S, acc-D for D) and deceleration time (dec-S for S, dec-D for D),
      respectively. Similarly, time intervals for both peaks of right ventricular
      inflow were analyzed regarding acceleration time (acc-E for E-wave, acc-A for A
      wave) and deceleration time (dec-E for E-wave, dec-A for A-wave), respectively.
      RESULTS: In the DV, acc-D and dec-D increased significantly with gestational age.
      In tricuspid valve, acc-E and acc-A showed a significant increase with
      gestational age. All parameters except acc-S showed significant negative
      correlations with fetal heart rate. CONCLUSION: With advancing gestational age,
      prolongation of the diastolic phase of DV-FVW and of the E-wave of tricuspid flow
      was observed, suggesting maturation of ventricular diastolic function. Time
      related analysis of Doppler signals of DV-FVW may provide detailed insights into
      fetal cardiac function.

PMID- 22653713
TI  - Effect of low-dose calcium supplements on bone loss in perimenopausal and
      postmenopausal Asian women: a randomized controlled trial.
AB  - Current standard-dose calcium supplements (eg, 1000 mg/d) may increase the risk
      for cardiovascular events. Effectiveness of lower-dose supplements in preventing
      bone loss should thus be considered. This study aimed to assess whether calcium
      supplements of 500 or 250 mg/d effectively prevent bone loss in perimenopausal
      and postmenopausal Japanese women. We recruited 450 Japanese women between 50 and
      75 years of age. They were randomly assigned to receive 500 mg of calcium (as
      calcium carbonate), 250 mg of calcium, or placebo daily. Medical examinations
      conducted three times over a 2-year follow-up period assessed bone mineral
      density (BMD) of the lumbar spine and femoral neck. One-factor repeated measures
      ANOVA was used for statistical tests. Subgroup analyses were also conducted.
      Average total daily calcium intake at baseline for the 418 subjects who underwent
      follow-up examinations was 493 mg/d. Intention-to-treat analysis showed less
      dramatic decreases in spinal BMD for the 500-mg/d calcium supplement group
      compared to the placebo group (1.2% difference over 2 years, p = 0.027). Per
      protocol analysis (>=80% compliance) revealed that spinal BMD for the 500-mg/d
      and 250-mg/d calcium supplement groups decreased less than the placebo group
      (1.6%, p = 0.010 and 1.0%, p = 0.078, respectively), and that femoral neck BMD
      for the 500-mg/d calcium supplement group decreased less relative to the placebo
      group (1.0%, p = 0.077). A low-dose calcium supplement of 500 mg/d can
      effectively slow lumbar spine bone loss in perimenopausal and postmenopausal
      women with habitually low calcium intake, but its effect on the femoral neck is
      less certain. Calcium supplementation dosage should thus be reassessed. (Clinical
      Trials Registry number: UMIN000001176).

PMID- 22653714
TI  - Ex vivo expansion of cord blood-CD34(+) cells using IGFBP2 and Angptl-5 impairs
      short-term lymphoid repopulation in vivo.
AB  - Cord blood-derived haematopoietic stem cells (CB-HSCs) are an attractive source
      for transplantation in haematopoietic disorders. However, the yield of CB-HSCs
      per graft is limited and often insufficient, particularly for the treatment of
      adult patients. Here we compare the capacity of three cytokine cocktails to
      expand CB-CD34(+) cells. Cells were cultured for 5 or 14 days in media
      supplemented with: (a) SCF, FL, IL-3 and IL-6 (SFLIL3/6); (b) SCF, TPO, FGF-1 and
      IL-6 (STFIL6); and (c) SCF, TPO, FGF-1, IGFBP2 and Angptl-5 (STFAI). We observed
      that STFAI-culture expansion sustained the most vigorous cell proliferation,
      maintenance of CD34(+) phenotype and colony-forming unit counts. In addition,
      STFAI-cultured cells had a potent ex vivo migration activity. STFAI-expanded
      cells were able to engraft NSG mice. However, no significant difference in
      overall engraftment was observed among the expansion cocktails. Assessment of
      short-term reconstitution using multilineage markers demonstrated that the STFAI
      cocktail for HSCs expansion greatly improved total cell expansion but may impair
      short-term lymphoid repopulation.

PMID- 22653716
TI  - [Patient safety - definition and epidemiology of adverse events, errors and
      incidents].
AB  - Multiple studies in the last years on patient safety brought this issue into
      focus for healthcare workers, but also politics and public. It is evident, that
      patient safety in health care is not longer a "nice to have", but an absolutely
      "must", analog others high risk industries. This article presents the most
      important basis principles of patient safety. The development from the error- to
      the safety culture is described. The terms adverse event, error and incident are
      defined as well other important terms and possible human pitfalls. At the end
      epidemiology correlations are presented, to underline the importance of patient
      safety in medicine. This article should help to understand the terminology of
      patient safety, to be able to understand the real important ideas and context of
      patient safety.

PMID- 22653715
TI  - Family relationships and troubled sleep among U.S. adults: examining the
      influences of contact frequency and relationship quality.
AB  - Sleep is essential for health and daily functioning, and social relationships may
      be a key social factor influencing sleep, yet sleep has been understudied in the
      literature on social relationships and health. This study used data from the
      National Survey of Midlife Development in the United States to examine
      associations between troubled sleep and family contact, social support, and
      strain. Results show that having strained family relationships is associated with
      more troubled sleep, while supportive family relationships are associated with
      less troubled sleep. Family strain is more consequential for sleep than support,
      and sleep troubles are greatest when family relationships are highly strained and
      provide inadequate emotional support. Family strain is also more harmful to sleep
      among individuals who are in frequent contact with family members. These findings
      underscore the importance of focusing on both negative and positive aspects of
      relationships and highlight the significance of family relationships for sleep.

PMID- 22653717
TI  - [CIRRNET(r) - learning from errors, a success story].
AB  - CIRRNET(r) is the network of local error-reporting systems of the Swiss Patient
      Safety Foundation. The network has been running since 2006 together with the
      Swiss Society for Anaesthesiology and Resuscitation (SGAR), and network
      participants currently include 39 healthcare institutions from all four different
      language regions of Switzerland. Further institutions can join at any time. Local
      error reports in CIRRNET(r) are bundled at a supraregional level, categorised in
      accordance with the WHO classification, and analysed by medical experts. The
      CIRRNET(r) database offers a solid pool of data with error reports from a wide
      range of medical specialist's areas and provides the basis for identifying
      relevant problem areas in patient safety. These problem areas are then processed
      in cooperation with specialists with extremely varied areas of expertise, and
      recommendations for avoiding these errors are developed by changing care
      processes (Quick-Alerts(r)). Having been approved by medical associations and
      professional medical societies, Quick-Alerts(r) are widely supported and well
      accepted in professional circles. The CIRRNET(r) database also enables any
      affiliated CIRRNET(r) participant to access all error reports in the 'closed user
      area' of the CIRRNET(r) homepage and to use these error reports for in-house
      training. A healthcare institution does not have to make every mistake itself -
      it can learn from the errors of others, compare notes with other healthcare
      institutions, and use existing knowledge to advance its own patient safety.

PMID- 22653718
TI  - [Assessment, frequency, causes, and prevention of medication errors - a critical
      analysis].
AB  - Medication errors are responsible for up to 50% of errors in healthcare.
      Therefore, they are an important target for the improvement of patient safety.
      The application of evidence-based methods for the analysis of institution
      specific medication safety hotspots is crucial. Recommended methods for the
      identification of medication safety problems have individual strengths and
      weaknesses, but there is little overlap. Consequently, a combination of methods
      is recommended. While the analysis of critical incident reporting systems
      preferentially identifies serious medication errors, trigger tool represents an
      effective and cost-efficient approach. Evidence-based data for improvement
      methods is limited. However, the implementation of clinical pharmacy services, IT
      tools (electronic prescribing, barcoding) and standardized double-check showed a
      significant impact on error reduction. In addition, the support of institutional
      leadership is an important prerequisite.

PMID- 22653719
TI  - [Patient safety in outpatient care - study of Swiss primary care offices].
AB  - Knowledge of the most frequent and relevant safety problems is necessary in order
      to identify areas of risk in patient safety and to specify need for action. For
      Switzerland, there was no data available that systematically describes the type
      and frequency of critical incidents in outpatient care. Due to differences in
      primary care systems world wide, the transfer of international data to the Swiss
      context is of limited validity. For this reason the Patient Safety Foundation
      conducted a research project in cooperation with partners from primary care
      practice. We analysed the frequency and severity of patient safety risks in
      primary care offices as well as the safety climate in those practices. Results of
      the survey show the following areas of risk are of high relevance: medication,
      triage by nurse at initial contact (by phone), diagnosis as well as failures to
      monitor patients in the office. In addition, errors in tests and therapeutic
      interventions should be prioritized for future action. Several differences
      between professional groups could be identified regarding the perception and
      estimation of critical incidents as with respect to the safety climate. In
      conclusion, physicians and nurses should be involved when analysing risks and
      developing measures in order to insure high quality standards in patient care.

PMID- 22653720
TI  - [Patients as vigilant partners - patient involvement in patient safety].
AB  - Patients can contribute to the improvement in patient safety. They are usually
      vigilant observers of the care they receive and can provide information about
      adverse events and safety-related processes. In addition, they can help to
      prevent errors by active engagement in safety. This potential for involvement in
      error prevention is increasingly acknowledged internationally. Educational
      material has been developed and can be used to instruct and motivate patients to
      monitor care for failures and errors and communicate their observations towards
      health care workers. Preliminary research suggests that this approach can be
      successful in improving patient safety.

PMID- 22653721
TI  - [Communication with patients about medical incidents].
AB  - Errors in medicine are common and often inevitable. They represent a dramatic
      situation for patients and their families. Thus, the physician-patient
      communication after a critical incident is crucial to prevent increased trauma.
      An error disclosure is a difficult, often overwhelming challenge for physicians.
      Doctors commonly experience enormous pressures from patient advocates and
      ethicists, who encourage full disclosure while risk managers and liability
      insurers demand restraint. Despite increasing institutional and legal
      protections, physicians are still reluctant to disclose errors to their patients.
      And those error disclosures that do occur often fail to meet patients'
      expectations. In fact, there is a substantial gap between what patients want to
      hear and what physicians typically disclose. Previous research has proposed a
      series of verbal messages doctors should communicate during error disclosures.
      However, considering the emotional content of such messages, patients likely
      derive much of the meaning from physicians' nonverbal behaviors. This article
      presents a detailed review of the existing literature on this topic area and
      discusses the verbal and nonverbal components that constitute a competent error
      disclosure in the medical field.

PMID- 22653722
TI  - ["Second victim" - error, crises and how to get out of it].
AB  - Medical errors do not only harm patients ("first victims"). Almost all health
      care professionals become a so-called "second victim" once in their career by
      being involved in a medical error. Studies show that error involvement can have a
      tremendous impact on health care workers leading to burnout, depression and
      professional crisis. Moreover persons involved in errors show a decline in job
      performance and jeopardize therefore patient safety. Blaming the person is one of
      the typical psychological reactions after an error happened as the attribution
      theory tells. The self-esteem gets stabilized if we can put blame on someone and
      pick out a scapegoat. But standing alone makes the emotional situation even
      worse. A vicious circle can evolve with tragic effect for the individual and
      negative implications for patient safety and the health care setting.

PMID- 22653723
TI  - Long-term survival and onset of granulomatous pneumonia after lung metastasectomy
      in a patient with non-muscle-invasive bladder cancer.
AB  - AIMS: This case report describes a first case of granulomatous pneumonia
      occurring at the same site of the previous lung metastasectomy in a patient with
      high-grade non-muscle-invasive bladder cancer (NMIBC), which was treated with
      bladder preservation therapy despite multiple recurrences and failure of
      intravesical bacillus Calmette-Guerin (BCG) therapy. CLINICAL CASE: We report a
      52-year-old woman who underwent transurethral surgery and BCG therapy for pT1, G3
      bladder cancer. Although cystectomy was recommended after BCG failure, the
      operation was not performed because of the patient's wish for bladder
      preservation. Eighteen months after the first surgery, computed tomography (CT)
      revealed solitary lung mass. Partial lobectomy which the patient underwent after
      chemotherapy revealed G3 metastatic urothelial carcinoma. Three years after lung
      metastasectomy, CT revealed lung mass at the same site of the previous lung
      metastasectomy. Dynamic contrast-enhanced magnetic resonance imaging showed the
      significantly enhanced lung mass, which indicated lung metastasis. However,
      lobectomy of the remnant lobe revealed that the lung mass was granulomatous
      pneumonia. Although no additional specific treatment was carried out, the patient
      remains free of disease for 53 months after surgery. CONCLUSIONS: Lung metastasis
      from NMIBC rarely occurs. Our case report confirms that lung metastasectomy in
      highly selected patients may contribute to long-term disease control. Moreover,
      our case report suggests that mycobacterial lung infections along the staple
      suture line rarely occur, and percutaneous biopsy should be considered under
      these circumstances to avoid the unnecessary operation.

PMID- 22653724
TI  - Views of healthcare professionals dealing with legal termination of pregnancy up
      to 12 WA in French-speaking Switzerland.
AB  - BACKGROUND: In 2002, by popular vote, Swiss citizens accepted to legalise
      termination of pregnancy (TOP), up to the 12th week of amenorrhoea (WA). As a
      result, the cantons formulated rules of application. In 2002, medical TOP was
      authorised. Health institutions then had to modify their procedures and
      practices. QUESTIONS UNDER STUDY/PRINCIPLES: What are the views of healthcare
      professionals on the modifications of procedures and practices implemented in
      French-speaking Switzerland? METHODS: Qualitative method: in-depth interviews
      with 77 healthcare professionals, including doctors, nurses and midwives, and
      sexual and reproductive health social workers. Voluntary participation. Thematic
      analysis with content analysis software. RESULTS: Most professionals have a
      balanced point of view on their practices. There is no point of view specific to
      each different category of professionals interviewed. They are unanimous on the
      elimination of the need for a second opinion. The points of view diverge on the
      usefulness of imposed waiting time to think before TOP, minors' access to TOP
      without parental consent, access to medical TOP and the right to refuse to
      practice TOP for personal reasons in public hospitals. CONCLUSIONS: The
      professionals do not question women's right to have TOP up to 12 WA, but they do
      diverge over procedures and practices. Institutional and cantonal cultures are
      probably behind these differences.

PMID- 22653725
TI  - Thyroid function and stress hormones in children with stress hyperglycemia.
AB  - The purpose of the study is to determine the prevalence of stress hyperglycemia
      and to investigate how thyroid and stress hormones alter during stress
      hyperglycemia in children admitted to pediatric emergency wards. A prospective
      cross-sectional study was conducted in children, less than 19 years old, who were
      admitted to pediatric emergency wards of Nemazee and Dastgheib Hospitals, Shiraz,
      Southern Iran. Those patients taking steroids, beta-agonists or intravenously
      administered glucose before venipuncture, and patients with diabetes mellitus
      (DM) or thyroid diseases were excluded. Children with blood glucose >= 150 mg/dL
      during admission were regarded as cases. The controls were age- and- sex-
      matched, euglycemic children. Stress hormones including cortisol, insulin, growth
      hormone, and prolactin were measured, and thyroid function was tested with a
      radioimmunoassay (RIA) method in all cases and controls. The results showed that
      among 1,054 screened children, 39 cases (3.7 %) had stress hyperglycemia and 89
      controls were included in the study. The occurrence of hyperglycemia was
      independent of sex, but it occurred mostly in children under 6 years old.
      Hyperglycemia occurred more frequently in patients with a positive family history
      of DM (odds ratio = 3.2, 95 % CI = 1.3-7.9, and P = 0.009). There were no
      significant differences between cases and controls regarding any hormones except
      higher cortisol, and lower total T3 and T4 in cases compared with controls.
      Neither of cases developed diabetes in the 24-month follow-up period. These
      findings led us to the conclusion that stress hyperglycemia is occasionally seen
      in critically ill patients. Among the stress hormones measured, only cortisol
      increased during hyperglycemia. It seems that hyperglycemia is not an important
      risk factor for future diabetes.

PMID- 22653726
TI  - Saturated free fatty acids: islet beta cell "stressERs".

PMID- 22653727
TI  - Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator
      complex.
AB  - The circadian clock in mammals is driven by an autoregulatory transcriptional
      feedback mechanism that takes approximately 24 hours to complete. A key component
      of this mechanism is a heterodimeric transcriptional activator consisting of two
      basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) domain protein subunits, CLOCK and
      BMAL1. Here, we report the crystal structure of a complex containing the mouse
      CLOCK:BMAL1 bHLH-PAS domains at 2.3 A resolution. The structure reveals an
      unusual asymmetric heterodimer with the three domains in each of the two subunits
      -bHLH, PAS-A, and PAS-B--tightly intertwined and involved in dimerization
      interactions, resulting in three distinct protein interfaces. Mutations that
      perturb the observed heterodimer interfaces affect the stability and activity of
      the CLOCK:BMAL1 complex as well as the periodicity of the circadian oscillator.
      The structure of the CLOCK:BMAL1 complex is a starting point for understanding at
      an atomic level the mechanism driving the mammalian circadian clock.

PMID- 22653728
TI  - Biochemistry. A lipid linchpin for Wnt-Fz docking.

PMID- 22653729
TI  - High-resolution protein structure determination by serial femtosecond
      crystallography.
AB  - Structure determination of proteins and other macromolecules has historically
      required the growth of high-quality crystals sufficiently large to diffract x
      rays efficiently while withstanding radiation damage. We applied serial
      femtosecond crystallography (SFX) using an x-ray free-electron laser (XFEL) to
      obtain high-resolution structural information from microcrystals (less than 1
      micrometer by 1 micrometer by 3 micrometers) of the well-characterized model
      protein lysozyme. The agreement with synchrotron data demonstrates the immediate
      relevance of SFX for analyzing the structure of the large group of difficult-to
      crystallize molecules.

PMID- 22653730
TI  - A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid
      noscapine.
AB  - Noscapine is an antitumor alkaloid from opium poppy that binds tubulin, arrests
      metaphase, and induces apoptosis in dividing human cells. Elucidation of the
      biosynthetic pathway will enable improvement in the commercial production of
      noscapine and related bioactive molecules. Transcriptomic analysis revealed the
      exclusive expression of 10 genes encoding five distinct enzyme classes in a high
      noscapine-producing poppy variety, HN1. Analysis of an F(2) mapping population
      indicated that these genes are tightly linked in HN1, and bacterial artificial
      chromosome sequencing confirmed that they exist as a complex gene cluster for
      plant alkaloids. Virus-induced gene silencing resulted in accumulation of pathway
      intermediates, allowing gene function to be linked to noscapine synthesis and a
      novel biosynthetic pathway to be proposed.

PMID- 22653731
TI  - Structural basis of Wnt recognition by Frizzled.
AB  - Wnts are lipid-modified morphogens that play critical roles in development
      principally through engagement of Frizzled receptors. The 3.25 angstrom structure
      of Xenopus Wnt8 (XWnt8) in complex with mouse Frizzled-8 (Fz8) cysteine-rich
      domain (CRD) reveals an unusual two-domain Wnt structure, not obviously related
      to known protein folds, resembling a "hand" with "thumb" and "index" fingers
      extended to grasp the Fz8-CRD at two distinct binding sites. One site is
      dominated by a palmitoleic acid lipid group projecting from serine 187 at the tip
      of Wnt's thumb into a deep groove in the Fz8-CRD. In the second binding site, the
      conserved tip of Wnt's "index finger" forms hydrophobic amino acid contacts with
      a depression on the opposite side of the Fz8-CRD. The conservation of amino acids
      in both interfaces appears to facilitate ligand-receptor cross-reactivity, which
      has important implications for understanding Wnt's functional pleiotropy and for
      developing Wnt-based drugs for cancer and regenerative medicine.

PMID- 22653734
TI  - Peptides as asymmetric catalysts and templates for the controlled formation of Ag
      nanoparticles.
AB  - The question whether peptides can fulfill functions for which nature utilizes
      large macromolecules is an overarching theme of the research in the Wennemers
      laboratory. The Zervas Award Lecture summarized our research on the development
      of peptides as asymmetric catalysts and templates for the controlled formation of
      silver nanoparticles. Tripeptides of the general type Pro-Pro-Xaa (Xaa = acidic
      amino acid) were presented that effectively catalyze aldol and conjugate addition
      reactions. These peptides are not only highly active, robust, and stereoselective
      catalysts but have also remarkable chemoselectivities. In the second part, short
      peptides that allow for the generation of silver nanoparticles in distinctly
      different sizes were presented.

PMID- 22653732
TI  - Membrane fusion intermediates via directional and full assembly of the SNARE
      complex.
AB  - Cellular membrane fusion is thought to proceed through intermediates including
      docking of apposed lipid bilayers, merging of proximal leaflets to form a
      hemifusion diaphragm, and fusion pore opening. A membrane-bridging four-helix
      complex of soluble N-ethylmaleimide-sensitive factor attachment protein receptors
      (SNAREs) mediates fusion. However, how assembly of the SNARE complex generates
      docking and other fusion intermediates is unknown. Using a cell-free reaction, we
      identified intermediates visually and then arrested the SNARE fusion machinery
      when fusion was about to begin. Partial and directional assembly of SNAREs
      tightly docked bilayers, but efficient fusion and an extended form of hemifusion
      required assembly beyond the core complex to the membrane-connecting linkers. We
      propose that straining of lipids at the edges of an extended docking zone
      initiates fusion.

PMID- 22653733
TI  - Broad heparin-binding haemagglutinin-specific cytokine and chemokine response in
      infants following Mycobacterium bovis BCG vaccination.
AB  - Heparin-binding haemagglutinin (HBHA)-specific immune responses have been linked
      to protection against tuberculosis (TB). We investigated the hypothesis that BCG
      vaccination of human infants primes an HBHA-specific response, using multiplex to
      measure secreted cytokines and chemokines following HBHA and Mycobacterium
      tuberculosis purified protein derivative (PPD) stimulation of diluted whole blood
      samples from BCG-vaccinated or -unvaccinated infants. Of 42 analytes measured, 24
      and 32 significant, BCG-associated increases were detected in response to HBHA
      and PPD, respectively. Both response profiles included Th-1, Th-2, Th-17 and
      inflammatory cytokines and chemokines (e.g. IFN-gamma, TNF-alpha, IL-5, IL-10, IL
      13, IL-17, MIP-1alpha and MIP-1beta). We also found that six of the seven
      responses most closely correlated with IFN-gamma were common to both HBHA and
      PPD. Notably, all HBHA-specific secretion of cytokines and chemokines from infant
      samples was dependent on previous BCG vaccination. Also, long-term persistence of
      HBHA-specific responses was found in adolescents with evidence of infant BCG
      vaccination. This study demonstrates for the first time BCG priming of an HBHA
      specific immune response in infants that is characterised by a broad cytokine and
      chemokine signature. It also suggests a number of BCG vaccination associated,
      HBHA-induced responses that should be useful for future studies of biomarkers of
      protection against TB.

PMID- 22653736
TI  - Images in endocrine pathology : oncocytic differentiation in a mixed
      adenoneuroendocrine carcinoma of the colon.

PMID- 22653735
TI  - Cognitive differences among depressed and non-depressed MCI participants: a
      project FRONTIER study.
AB  - OBJECTIVE: Depression is the most commonly reported psychiatric symptom in
      patients with mild cognitive impairment (MCI). However, more research is needed
      examining the impact of depression on cognitive functioning in MCI patients. The
      purpose of this study was to examine differences in cognitive functioning in a
      sample of community- based, depressed, and non-depressed MCI patients. METHODS:
      One hundred and five participants with MCI were included in this study.
      Participants were recruited from Project FRONTIER, a study of rural health.
      Depression was assessed via the Geriatric Depression Scale (GDS-30), and
      cognition was measured using the Repeatable Battery for the Assessment of
      Neuropsychological Status. RESULTS: The results indicated that depressed MCI
      participants performed significantly worse than their non-depressed counterparts
      on several cognitive measures. MCI participants with depression scored
      significantly lower on immediate memory (t = 3.4, p < 0.01) and delayed memory (t
      = 2.8, p < 0.01) indices than their non-depressed counterparts. CONCLUSIONS: The
      results of this study indicated that MCI participants with depression experienced
      greater deficits in cognitive functioning than their non-depressed counterparts.
      Depressed MCI participants exhibited greater deficits in both immediate and
      delayed memory. Thus, identifying and treating depression in individuals with MCI
      may improve memory and cognitive functioning.

PMID- 22653737
TI  - Duplication of 18q21.32-q22.3 identified in a stillborn and two relatives with
      minimal dysmorphic features.

PMID- 22653738
TI  - Shear stress influences the pluripotency of murine embryonic stem cells in
      stirred suspension bioreactors.
AB  - Pluripotent embryonic stem cells (ESCs) have been used increasingly in research
      as primary material for various tissue-engineering applications. Pluripotency, or
      the ability to give rise to all cells of the body, is an important characteristic
      of ESCs. Traditional methods use leukaemia inhibitory factor (LIF) to maintain
      murine embryonic stem cell (mESC) pluripotency in static and bioreactor cultures.
      When LIF is removed from mESCs in static cultures, pluripotency genes are
      downregulated and the cultures will spontaneously differentiate. Recently we have
      shown the maintenance of pluripotency gene expression of mESCs in stirred
      suspension bioreactors during differentiation experiments in the absence of LIF.
      This is undesired in a differentiation experiment, where the goal is
      downregulation of pluripotency gene expression and upregulation of gene
      expression characteristic to the differentiation. Thus, the objective of this
      study was to examine how effectively different levels of shear stress [100 rpm (6
      dyne/cm(2) ), 60 rpm (3 dyne/cm(2) )] maintained and influenced pluripotency in
      suspension bioreactors. The pluripotency markers Oct-4, Nanog, Sox-2 and Rex-1
      were assessed using gene expression profiles and flow-cytometry analysis and
      showed that shear stress does maintain and influence the gene expression of
      certain pluripotency markers. Some significant differences between the two levels
      of shear stress were seen and the combination of shear stress and LIF was
      observed to synergistically increase the expression of certain pluripotency
      markers. Overall, this study provides a better understanding of the environmental
      conditions within suspension bioreactors and how these conditions affect the
      pluripotency of mESCs.

PMID- 22653739
TI  - Age-specific reference ranges for prostate-specific antigen among healthy Syrian
      men.
AB  - Prostate-specific antigen (PSA) has become the most useful serum tumor marker in
      adjunct to digital rectal examination (DRE) for the management of prostate cancer
      (PC). The currently cited reference range of normal PSA levels (between 0 and 4.0
      ng/mL) is deficient in terms of both sensitivity and specificity. Age-adjusted
      PSA have been proposed as an alternative to serum PSA. The primary objective of
      the present study is to determine the age-specific PSA and the percentage of free
      PSA (%FPSA) in healthy Syrian men. A total of 3,000 healthy Syrian men over 40
      years old participated in this study. All men were asked to have total serum
      (TPSA) and free PSA (FPSA) tested, a DRE, and, when recommended, a prostate
      biopsy. Serum TPSA levels correlated with age (r=0.30, p<0.001). The 95th
      percentile TPSA values ranged from 1.7 ng/mL in the age group 40-49 years to 5.8
      ng/mL in the group 70-80 years. The general pattern for medians and the
      percentile values for FPSA across age groups were similar to those seen for TPSA
      concentrations (r=0.37, p<0.001). However, the %FPSA was fairly constant across
      age groups except for the higher ratios in the youngest age group. These findings
      confirm that the serum TPSA and FPSA levels correlate with age. Interestingly,
      however, Syrian men have lower PSA values compared with other races. Racial
      differences of PSA concentrations were observed. Our results may help increasing
      the sensitivity and specificity of PSA measurements in the diagnosis of prostate
      cancer in Syria and probably in the surrounding regions.

PMID- 22653740
TI  - Clinical relevance of human mammaglobin mRNA in pleural effusion from patients
      undergoing thoracoscopy: a pilot study.
AB  - BACKGROUND: human mammaglobin (hMAM) expression has been reported in pleural
      effusions (PE). The aim of this study was to assess the clinical relevance of
      hMAM mRNA in PE from patients who underwent thoracoscopy.? MATERIAL AND METHODS:
      A total of 288 patients with PE were studied, 155 of which were diagnosed with
      malignant and 133 with non-malignant diseases by thoracoscopy. Cells from PE were
      analyzed by nested hMAM RT-PCR. Statistical analyses were performed to evaluate
      the diagnostic performance parameters (DPP), the association between hMAM
      expression and benign or malignant status and the relative risk of cancer for
      patients with negative thoracoscopy showing hMAM positivity.? RESULTS: hMAM mRNA
      was found in 68/288 (23.6%) PE samples of which 51 were from the 155 patients
      diagnosed with malignant diseases and 17 were from the 133 patients diagnosed
      with non-malignant diseases. A significant correlation between hMAM expression
      and malignancy was found (OR=3.04) and the DPP were as follows:
      sensitivity=32.9%, specificity=87.2%, accuracy=58.0%, positive predictive
      value=75.0% and negative predictive value=52.7%. Among the patients with negative
      thoracoscopy (n=133), 5/17 (29.4%) hMAM-positive patients had or developed a
      tumor during the 18-month follow up period, as compared to 10/116 (8.6%) hMAM
      negative patients (relative risk of 4.6 for developing a malignancy).?
      CONCLUSION: These findings suggest a possible application of hMAM RT-PCR
      detection in PE as to identify a false-negative thoracoscopy in non-specific
      pleuritis.

PMID- 22653741
TI  - Presence of CSE1L protein in urine of patients with urinary bladder urothelial
      carcinomas.
AB  - The chromosome segregation 1-like (CSE1L) protein is highly expressed in most
      cancers and has been shown to be secreted by tumor cells. We studied the presence
      of CSE1L in the urine of patients with bladder urothelial carcinomas. The results
      of our immunohistochemical analysis showed a high expression of CSE1L in bladder
      cancer specimens, while the normal bladder specimens only showed a very faint
      staining in some cells. Immunoblotting showed that CSE1L was present in urine of
      patients with bladder cancer. Urinary CSE1L-positive cases were detected in 95%
      (57/60) of patients with bladder urothelial carcinomas or the atypical/suspicious
      cases with urothelial atypia. No CSE1L was detected in urine of healthy controls
      (p<0.01). Our results suggest that urinary CSE1L deserves further evaluation for
      the screening of bladder cancer.

PMID- 22653742
TI  - Urinary 5-HIAA excretion is not increased in patients with head and neck
      paragangliomas.
AB  - BACKGROUND: Case reports have documented carcinoid-like features in head and neck
      paragangliomas (HNPGLs), which, in addition to catecholamine storing granules,
      may also contain granules with serotonin. Serotonin is metabolized to 5
      hydroxyindoleacetic acid (5-HIAA). ? AIM: To assess the urinary excretion rates
      of 5-HIAA and catecholamines in HNPGL patients.? METHODS: In 114 consecutive
      HNPGL patients, normetanephrine, metanephrine, norepinephrine, epinephrine, VMA,
      dopamine, 3-methoxytyramine and 5-HIAA excretion rates were measured in two 24
      hour urinary samples. Increased excretion rates were defined as an increase of
      the average hormone excretion rate of 2 urine samples above the reference range.
      In all patients with catecholamine excess, intrathoracic and abdominal
      paragangliomas were excluded by 123I-MIBG scintigraphy, MRI and/or CT. Genetic
      screening for mutations in genes of the succinate dehydrogenase (SDH) family was
      performed. ? RESULTS: Mean urinary 5-HIAA excretion rate was 14+/-9 MUmol/24
      hours (reference range 10-44 MUmol/24 hours). Urinary 5-HIAA excretion was
      slightly increased in only 1 patient (48 MUmol/24 hours). None of the 50 patients
      (44%) with increased urinary excretion rates of catecholamines and/or their
      metabolites had elevated 5-HIAA excretion.? CONCLUSION: Urinary 5-HIAA excretion
      is within the normal reference range in almost all HNPGL patients. Therefore,
      this parameter has no clinical relevance in the routine clinical assessment of
      HNPGL patients.

PMID- 22653743
TI  - Breast cancer survival and immunohistochemical similarities between primary and
      metastatic sites, as a surrogate marker for the cancer self-seeding.

PMID- 22653744
TI  - BAT-25 polymorphism in Chinese from Jiangsu province and its implication for
      locus microsatellite instability screening.
AB  - BACKGROUND: Colorectal cancer is one of the most common tumors with high
      mortality in China. Microsatellite instability (MSI) analysis is important for
      the diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) and for the
      prediction of 5-FU chemotherapy efficiency of colorectal tumors, especially in
      terms of therapeutic response and overall survival rates. Among the MSI markers
      recommended by the NIH/NCI, BAT-25 has been extensively studied for its major
      role in MSI. BAT-25 presents different polymorphisms in different ethnic
      populations and studies of its polymorphisms in the Chinese population are still
      very limited. AIMS: To analyze the frequency of constitutive polymorphic
      variation at the BAT-25 locus in Chinese from Jiangsu Province and its
      implication for locus MSI screening. METHODS: The frequency of allelic variation
      at the BAT-25 locus of cervical cells from 500 healthy women and blood from 16
      healthy males was assessed by direct sequencing. Twenty samples were also
      analyzed by fragment analysis. DNA extracted from blood of 94 patients with
      gastrointestinal cancer or endometrial cancer was analyzed by fragment analysis.
      RESULTS: After comparison with the sequencing results, the more frequent allele
      lengths were 126-127 bp, 128-129 bp, 129-130 bp, respectively consistent with the
      24 poly(T) (T24), T25 and T26 alleles. At the BAT-25 locus, 516 healthy
      individuals had respectively 1.36%, 97.28% and 1.36% of the T24, T25 and T26.
      Whereas for the 94 cancer patients allelic frequencies were 0.53%, 1.06%, 96.8%,
      1.6% for T15, T24, T25 and T26 alleles respectively. Sixteen healthy males had
      only the T25 allele and heterozygous T15 was only found in 1 male patient with
      colon cancer. CONCLUSION: We established the relation between fragment length and
      thymine repeats in BAT-25. The results showed that the BAT-25 locus is
      quasimonomorphic in Chinese from Jiangsu province. Moreover we showed that
      variant alleles of BAT-25 were found more likely in blood from cancer patients
      than in healthy individuals, suggesting the need to perform comparative studies
      between tumor and blood, or normal tissue, as to obtain a correct MSI
      identification.

PMID- 22653745
TI  - Insertion/deletion polymorphisms are convenient and reliable markers to assess
      chromosomal instability in human tumors.
AB  - Chromosomal instability (CIN) is frequently associated with a poor outcome in
      human carcinomas. The genomes of the main human malignancies are well defined as
      hundreds of tumors have been characterized by arrays. Targeting the appropriate
      chromosomes with set of markers appears as a realistic approach for CIN
      assessment. We decided to test the reliability of different insertion/deletion
      (InDel) polymorphisms to detect allelic loss in a subset of previously
      characterized hepatocellular carcinomas (HCC). To this aim 3 kinds of markers, L1
      insertion (n=1), Alu insertions (n=4) and Marshfield InDel (MID, n=8) markers,
      were tested on a series of 68 paired HCC/non-tumor liver samples that were
      previously characterized for loss of heterozygosity (LOH). All markers were
      analyzed on agarose gels and some were tested with the high resolution melting
      (HRM) technique. Heterozygosity of the tested markers was high with a mean of
      0.489 and a range of 0.265-0.525. Using 6 markers for chromosome 8p, the
      sensitivity of the method was high. LOH was detected in all samples known to be
      affected (n=34) whereas retention was found in 29/30 samples (specificity of
      96.6%). Finally, the HRM analysis applied to 2 MID markers provided consistent
      profiles enabling closed-tube determination of chromosomes 17p and 18q status.
      Overall, our work suggests that different types of InDel markers are suitable for
      CIN detection in human tumors and may provide convenient and useful information
      for basic or translational research as well as for future applications in
      clinical practice.

PMID- 22653746
TI  - Why depressive symptoms cause distress: the clients' perspective.
AB  - BACKGROUND: Depressive symptoms are associated with distress, but research has
      not focused on the processes underlying this association. METHOD: We interviewed
      18 patients experiencing depressive symptoms to identify the various reasons why
      depressive symptoms cause distress. Digital recordings were transcribed and
      grounded theory methods were used in analyzing the data and building theory.
      RESULTS: We identified 14 reasons for why patients find depressive symptoms
      distressing. These reasons frequently were particular thoughts, behaviors, or
      subsequent outcomes in response to the symptom; in other cases, the experience of
      the symptom itself directly caused distress. CONCLUSIONS: We present a general
      model of direct and indirect symptom-distress relationships that may help target
      clinical interventions for depression.

PMID- 22653747
TI  - Interleukin-1, inflammasomes, autoinflammation and the skin.
AB  - Interleukin 1, one of the first cytokines discovered in the 1980s, and a potent
      mediator of fever, pain and inflammation, is at present experiencing a revival in
      biology and medicine. Whereas the mechanism of activation and secretion of
      interleukin 1beta, which critically regulates the function of this molecule, has
      remained mysterious for some 30 years following its discovery, the identification
      of a new cytoplasmic complex of proteins regulating IL-1beta activation and
      secretion has carried our understanding of the role of IL1 in biology and disease
      one big step further. The inflammasomes, recently identified innate immune
      complexes that sense intracellular danger- (e.g. uric acid, ATP, cytoplasmic DNA)
      or pathogen-associated molecular patterns (e.g. muramyl dipeptide, flagellin,
      anthrax lethal toxin), are now known to be responsible for triggering
      inflammation in response to several molecular patterns, including, for example,
      uric acid, a danger-associated molecular pattern and trigger of gout.
      Dysregulation of inflammasome function is however also the cause of a family of
      genetic autoinflammatory diseases known as cryopyrin-associated periodic
      syndromes (CAPS) characterised by recurrent episodes of fever, urticarial-like
      skin lesions, systemic inflammation and arthritis. In mouse models recapitulating
      mutations observed in CAPS, neutrophilic inflammation of the skin is a cardinal
      feature, in a manner similar to several autoinflammatory diseases with skin
      involvement such as PAPA (pyoderma gangrenosum, acne and pyogenic arthritis) and
      Schnitzler's syndrome, in which IL-1beta very probably plays a pathogenic role.
      In this article the role of the inflammasome in IL-1 biology, autoinflammation
      and disease is reviewed, together with new avenues for the therapy of these
      diseases.

PMID- 22653748
TI  - New insights into the heating mechanisms and self-regulating abilities of
      manganite perovskite nanoparticles suitable for magnetic fluid hyperthermia.
AB  - The heating and self-regulating abilities of La(1-x)Sr(x)MnO(3+Delta)
      ferromagnetic nanoparticles for magnetic fluid hyperthermia are studied. The
      samples, synthesized by the Glycine Nitrate Process, present non-agglomerated
      particles but are partially constituted by polycrystalline nanoparticles,
      displaying average crystallite diameters ranging from 21 to 31 nm. The strontium
      content of these nanoparticles, between 0.14 and 0.39, is associated with non
      stoichiometry effects in the materials, and both govern their Curie temperatures
      (T(C)), which range between 13 and 86  degrees C, respectively. Heating
      experiments carried out on samples suspended in an aqueous agarose gel and with
      different alternating magnetic fields derive unexpected maximum temperatures that
      cannot be explained on the basis of static magnetization data. The measurement of
      the thermal dependence of the specific absorption rate (SAR) of nanopowders by
      adiabatic magnetothermia reveals the existence of a dissipation peak just below
      T(C), which is assigned to a Hopkinson peak. This thermal dependence of SAR,
      together with a simple thermal model that considers a linear approximation for
      the heat power losses, is crucial to clarify the behavior observed in heating
      experiments and also to discuss the possibilities of the samples as self
      regulating hyperthermia mediators. This analysis emphasizes that, for the correct
      design of a self-regulating system, the heat power losses determined by the
      surrounding conditions must be taken into account as well as the heating capacity
      of the magnetic nanoparticles.

PMID- 22653750
TI  - Comparison of the potency of a variety of beta-glucans to induce cytokine
      production in human whole blood.
AB  - beta-Glucans are components of fungal cell walls and potent stimulants of innate
      immunity. The majority of research on biological activities of glucans has
      focused on beta-(1->3)-glucans, which have been implicated in relation to fungal
      exposure-associated respiratory symptoms and as important stimulatory agents in
      anti-fungal immune responses. Fungi-and bacteria and plants-produce a wide
      variety of glucans with vast differences in the proportion and arrangement of
      their beta-(1->3)-, -(1->4)- and -(1->6)-glycosidic linkages. Thus far, the pro
      inflammatory potential of different beta-glucans has not been studied within the
      same experimental model. Therefore, we compared the potency of 13 different
      glucan preparations to induce in vitro production of IL-1beta, IL-6, IL-8 and TNF
      alpha in human, whole blood cultures. The strongest inducers of all cytokines
      were pustulan [beta-(1->6)-glucan], lichenan [beta-(1->3)-(1->4)-glucan],
      xyloglucan [beta-(1->4)-glucan] and pullulan [alpha-(1->4)-(1->6)-glucan].
      Moderate-to-strong cytokine production was observed for curdlan [beta-(1->3)
      glucan], baker's yeast glucan [beta-(1->3)-(1->6)-glucan] and barley glucan [beta
      (1->3)-(1->4)-glucan], while all other glucan preparations induced very low, or
      no, detectable levels of cytokines. We therefore conclude that innate immunity
      reactions are not exclusively induced by beta-(1->3)-glucans, but also by beta-(1
      >6)- and beta-(1->4)-structures. Thus, not only beta-(1->3)-glucan, but also
      other beta-glucans and particularly beta-(1->6)-glucans should be considered in
      future research.

PMID- 22653751
TI  - Globozoospermia is mainly due to DPY19L2 deletion via non-allelic homologous
      recombination involving two recombination hotspots.
AB  - To date, mutations in two genes, SPATA16 and DPY19L2, have been identified as
      responsible for a severe teratozoospermia, namely globozoospermia. The two
      initial descriptions of the DPY19L2 deletion lead to a very different rate of
      occurrence of this mutation among globospermic patients. In order to better
      estimate the contribution of DPY19L2 in globozoospermia, we screened a larger
      cohort including 64 globozoospermic patients. Twenty of the new patients were
      homozygous for the DPY19L2 deletion, and 7 were compound heterozygous for both
      this deletion and a point mutation. We also identified four additional mutated
      patients. The final mutation load in our cohort is 66.7% (36 out of 54). Out of
      36 mutated patients, 69.4% are homozygous deleted, 19.4% heterozygous composite
      and 11.1% showed a homozygous point mutation. The mechanism underlying the
      deletion is a non-allelic homologous recombination (NAHR) between the flanking
      low-copy repeats. Here, we characterized a total of nine breakpoints for the
      DPY19L2 NAHR-driven deletion that clustered in two recombination hotspots, both
      containing direct repeat elements (AluSq2 in hotspot 1, THE1B in hotspot 2).
      Globozoospermia can be considered as a new genomic disorder. This study confirms
      that DPY19L2 is the major gene responsible for globozoospermia and enlarges the
      spectrum of possible mutations in the gene. This is a major finding and should
      contribute to the development of an efficient molecular diagnosis strategy for
      globozoospermia.

PMID- 22653752
TI  - Early complex I assembly defects result in rapid turnover of the ND1 subunit.
AB  - Complex I (CI, NADH ubiquinone oxidoreductase), the largest complex of the
      respiratory chain, is composed of 45 structural subunits, 7 of which are encoded
      in mtDNA. At least 10 factors necessary for holoenzyme assembly have been
      identified; however, the specific roles of most of them are not well understood.
      We investigated the role of NDUFAF3, NDUFAF4, C8orf38 and C20orf7, four early
      assembly factors, in the translation of the mtDNA-encoded CI structural subunits.
      Transient, or stable, siRNA-mediated knock-down of any of these factors abrogated
      the assembly of CI, and resulted in a specific decrease in the labeling of the
      ND1 subunit in a pulse translation experiment, whereas knock-down of NDUFAF2, a
      late assembly factor, did not affect ND1 translation. Pulse-chase experiments in
      cells knocked down for NDUFAF3 showed that the half-life of ND1 in the chase was
      reduced 4-fold, fully accounting for the decrease in pulse labeling. Transient,
      short-term knock-down of the m-AAA protease AGF3L2 in cells that had been
      depleted of any of the early CI assembly factors completely rescued the ND1
      labeling phenotype, confirming that it is not a synthesis defect, but rather
      results from rapid proteolysis of newly synthesized ND1. NDUFAF3 co
      immunoprecipitated with NDUFAF4, and three matrix arm structural subunits
      (NDUFS2, NDUFA9, NDUFS3) that are found in a 400 kDa assembly intermediate
      containing ND1. These data suggest that the four early CI assembly factors have
      non-redundant functions in the assembly of a module that docks and stabilizes
      newly synthesized ND1, nucleating assembly of the holoenzyme.

PMID- 22653753
TI  - Postnatal inactivation reveals enhanced requirement for MeCP2 at distinct age
      windows.
AB  - Rett Syndrome is a neurological disorder caused by mutations in the X-linked
      MECP2 gene. Mouse models where Mecp2 is inactivated or mutated recapitulate
      several features of the disorder and have demonstrated a requirement for the
      protein to ensure brain function in adult mice. We deleted the Mecp2 gene in ~80%
      of brain cells at three postnatal ages to determine whether the need for MeCP2
      varies with age. Inactivation at all three time points induced Rett-like
      phenotypes and caused premature death of the animals. We find two threshold ages
      beyond which the requirement for MeCP2 markedly increases in stringency. The
      earlier threshold (8-14 weeks), when inactivated mice develop symptoms,
      represents early adulthood in the mouse and coincides with the period when Mecp2
      null mice exhibit terminal symptoms. Unexpectedly, we identified a later age
      threshold (30-45 weeks) beyond which an 80% reduction in MeCP2 is incompatible
      with life. This finding suggests an enhanced role for MeCP2 in the aging brain.

PMID- 22653754
TI  - The structure of affective symptomatology in older adults with osteoarthritis.
AB  - OBJECTIVE: To examine the structure of symptoms of affective disorder among older
      adults with a chronic health problem (osteoarthritis) and to explore cross
      sectional and longitudinal associations of obtained affective symptom clusters
      with key health outcomes (pain, functional disability, perceived health).
      METHODS: One-year longitudinal study of older adults with diagnosed
      osteoarthritis of the knee. Symptoms of DSM depression and anxiety were assessed
      in a research diagnostic interview by using a DSM-IV symptom checklist; self
      reports captured demographic characteristics, objective health, pain, disability,
      and perceived health. Confirmatory factor analysis tested comparability of
      affective symptom structure in this sample to findings of previous research;
      ordinary least squares regression examined cross-sectional and longitudinal
      associations of affective symptoms with health outcomes, controlling for
      demographics and objective health. RESULTS: The current sample displayed an
      affective symptom structure comparable with that observed in previous research,
      with symptoms clustering into depressed mood (DM), somatic symptoms (SS), and
      psychic anxiety (PA) factors. DM was cross-sectionally associated with pain and
      disability and marginally with perceived health; SS predicted current pain and
      perceived health. Only DM predicted 1 year change in disability and perceived
      health (but not pain). CONCLUSIONS: This research confirms the role of SS of
      distress in fueling disability and perceived ill health among older adults who
      are chronically ill. However, it is DM that drives changes in perceived health
      and functional ability.

PMID- 22653755
TI  - Maternal genetic effect in DNA analysis: egg on your traits.
AB  - A dilemma of penetrance parallels the uncertainty principle as array analyses
      uncover a disturbing continuity of human molecular variation. Among mechanisms
      for altered penetrance is maternal genetic effect, hypothesized to explain mother
      offspring discordance from 12/13 translocation [Wilson et al., 1991] and
      important to consider when confronting identical genetic changes in normal
      mothers and their abnormal children. A boy with developmental delays, autistic
      features, minimal dysmorphology, and maternally inherited 17p13.3
      microduplication could exemplify maternal genetic effect, as could a boy with
      altered brain pattern and maternally inherited Sonic Hedgehog mutation reported
      by Schell-Apacik et al. [2009]. Maternal genetic effects, characterized in fly,
      fish, and mouse, are important to consider in human DNA analysis so that
      identical findings in mother and child are not routinely dismissed as benign
      variations. Suspect families can define relevant maternal-zygote transition (MZT)
      genes, provide assays for oocyte function and disruption, and shift anomaly
      emphasis from pattern recognition to pattern restoration.

PMID- 22653756
TI  - MAGE-4 gene m-RNA and TGF in blood as potential biochemical markers for HCC in
      HCV-infected patients.
AB  - Progression from chronic hepatitis C virus infection to cirrhosis then to
      hepatocellular carcinoma usually results in some protein changes in peripheral
      blood. We evaluated MAGE-4 mRNA, TGFbeta1 and AFP in peripheral blood as
      potential biochemical markers for diagnosis and prognosis of some complications
      of HCV infection. MAGE-4 mRNA in blood by reverse transcription polymerase chain
      reaction, serum TGF-Beta1 and AFP by ELISA was assayed in seventy-five
      individuals who were classified into five groups: group I (control) comprised
      fifteen apparently healthy volunteers, group II involved fifteen HCV-infected
      patients without cirrhosis, group III involved fifteen HCV fifteen HCV-infected
      patients with cirrhosis, group IV included fifteen HCV-infected patients with
      cirrhosis and early stage HCC, and group V included fifteen HCV cirrhotic
      patients and late-stage HCC. We found that the frequency of positivity of MAGE-4
      among the late hepatoma group was 40 %, while in the early hepatoma group the
      positivity was 6.7 %. The results for TGF-Beta1 revealed a significant increase
      in serum TGF-Beta1 in groups IV and V as compared to control, II, III groups. The
      obtained results of AFP showed a significant positive increase in serum AFP in
      groups IV and V when compared to groups II and III. Detection of MAGE-4
      transcripts in blood, especially with follow-up survey, may help to predict the
      prognosis and monitoring of the response to the therapy, and serum TGF-Beta1
      level in HCC patients is directly correlated with metastasis and recurrence of
      tumors and increases gradually with the progression of HCC.

PMID- 22653757
TI  - Quantification of homocysteine-related metabolites and the role of betaine
      homocysteine S-methyltransferase in HepG2 cells.
AB  - We optimized and validated a rapid and sensitive liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method for the quantification of six metabolites of
      homocysteine metabolism: homocysteine, methionine, cysteine, S
      adenosylmethionine, S-adenosylhomocysteine and betaine. The detection limits for
      these metabolites were in the nanomolar range, and the intra- and inter-day
      precisions were lower than 20% of the relative standard deviations. The method
      was specifically designed for the determination of the intracellular
      concentrations of the metabolites in cultured cells. To study the role of betaine
      homocysteine S-methyltransferase (BHMT), HepG2 cells and HepG2 cells that were
      stably transfected with BHMT ((BHMT) HepG2) were treated with homocysteine or
      with a specific inhibitor of BHMT, and metabolite levels were subsequently
      measured. Severely compromised methyl group metabolism in the HepG2 cells, which
      is typical of cancer-derived cells, prevented clear evaluation of the changes
      caused by the external manipulations of homocysteine metabolism. However, the
      ease of handling these cells and the almost unlimited source of experimental
      material supplied by cells in permanent culture allowed us to develop a reliable
      methodology. The precautions concerning intracellular metabolite determinations
      using LC-MS/MS in cultured cells that are expressed in this work will have global
      validity for future metabolomics studies.

PMID- 22653758
TI  - Recent advances in therapeutic bronchoscopy.
AB  - Therapeutic bronchoscopy has come a long way from removal of foreign bodies to
      minimally invasive techniques in management of diseases like lung cancer, chronic
      obstructive pulmonary disease and asthma. This article discusses the exciting new
      techniques of therapeutic bronchoscopy namely; bronchoscopic lung volume
      reduction, bronchial thermoplasty, radiofrequency ablation, and use of fiducial
      markers in external beam irradiation.

PMID- 22653759
TI  - Self-efficacy's influence on student academic achievement in the medical anatomy
      curriculum.
AB  - Self-efficacy is defined as a person's beliefs in his or her own abilities to
      successfully complete a task and has been shown to influence student motivation
      and academic behaviors. More specifically, anatomical self-efficacy is defined as
      an individual's judgment of his or her ability to successfully complete tasks
      related to the anatomy curriculum; these include dissecting, learning anatomical
      concepts, and applying anatomical knowledge to clinical situations. The purpose
      of this study was to investigate the influence of anatomical self-efficacy on the
      academic performance of students enrolled in a medical gross anatomy course. To
      obtain students' anatomical self-efficacy ratings, surveys containing the same
      anatomical self-efficacy instrument were completed by first-year medical students
      at a southeastern United States allopathic medical school after each of four
      gross anatomy assessments. Additional data collected included student demographic
      information, Medical College Admission Test((r)) (MCAT((r))) scores, and anatomy
      assessment scores, both written examination and laboratory practical. To
      investigate the potential predictive nature of self-efficacy for academic
      performance on both the written examination and the laboratory practical
      components of medical anatomy assessments, hierarchical linear regression
      analyses were conducted. For these analyses, academic ability (defined as the sum
      of the physical sciences and biological sciences MCAT scores) was controlled. The
      results of the hierarchical linear regressions indicated that all four laboratory
      practical scores were predicted by the corresponding self-efficacy ratings, while
      two (i.e., thorax/abdomen and pelvis/lower limb) of the four written examination
      scores were predicted by the corresponding self-efficacy ratings (P <= 0.05).

PMID- 22653760
TI  - Comparison of long-term variability of retinal nerve fiber layer measurements
      made with the RTVue OCT and scanning laser polarimetry.
AB  - Purpose. To compare long-term variability of retinal nerve fiber layer thickness
      (RNFLT) measurements made with the RTVue-100 Fourier-domain optical coherence
      tomograph (RTVue-OCT) and scanning laser polarimetry with variable (GDx-VCC) and
      enhanced (GDx-ECC) corneal compensation. Methods. One eye each of 110 Caucasian
      patients (17 healthy, 20 ocular hypertensive, 22 preperimetric, and 51 perimetric
      glaucoma eyes, of which 10 showed visual field progression) were imaged
      prospectively at 6-month intervals for 1.5 to 3 years. Results. Median change of
      Octopus visual field mean defect was -0.300 dB/y for the controls, -0.120 dB/y
      for perimetric glaucoma group, and 1.231 dB/y  for the 10 functionally
      progressing perimetric glaucoma eyes. Relative (%) variance of all RNFLT
      parameters measured with RTVue-OCT was significantly (p<<0.001) smaller than that
      with both of the GDx methods. Relative RNFLT progression slopes (% change/y) did
      not differ significantly between the methods. Relative variance of the RNFLT
      parameters did not differ between the control and perimetric glaucoma group with
      RTVue-OCT, but for most parameters it was consistently higher for perimetric
      glaucoma with both GDx methods (p=0.01). Relative RNFLT progression slopes,
      however, did not separate the control and perimetric glaucoma eyes with either
      method. Conclusions. Long-term RNFLT measurements are less variable with the
      RTVue-OCT than with GDx-VCC and GDx-ECC. Long-term measurement variability is
      higher in perimetric glaucoma than in healthy eyes with both GDx methods, but no
      similar between-group difference is seen with RTvue-OCT. None of the tested
      methods separated the rate of progression between healthy and well-controlled
      perimetric glaucoma eyes in 1.5 to 3 years follow-up.

PMID- 22653761
TI  - Efficacy and tolerance of levodopa to treat amblyopia: a systematic review and
      meta-analysis.
AB  - Purpose. Amblyopia is the leading cause of visual impairment in children,
      affecting up to 4% of the general population. Several clinical trials evaluated
      the efficacy of levodopa versus placebo in treating amblyopia. However, the
      results appeared contradictory, suggesting both beneficial and ineffective. The
      aim of this study was to address the efficacy and tolerance of levodopa on
      amblyopia. Methods. Randomized controlled trials were identified and extracted
      from PubMed, EMBASE, Web of Science, and the Cochrane library. The quality of
      included trials was assessed by using Jadad score and heterogeneity was analyzed
      using chi-square test. Both efficacy and tolerance endpoints were evaluated. Data
      were extracted and analyzed using standard meta-analysis. Results. A total of 6
      trials were identified from the search strategy. The pooled mean difference of
      endpoint logMAR of levodopa versus placebo was -0.11 (95% confidence interval 
      0.19~-0.02, p=0.01). Amblyopic patients receiving levodopa did not show
      significantly higher frequent adverse events than those receiving placebo.
      Conclusions. The use of levodopa is an effective and safe option for the
      treatment of amblyopia, and levodopa can be considered as first-line treatment of
      amblyopia.

PMID- 22653762
TI  - The effect of glycemic control on visual and anatomic outcomes in response to
      therapy for diabetic macular edema.
AB  - Purpose. To evaluate the effect of glycemic control on response to therapy of
      diabetic clinically significant macular edema (CSME). Methods. Patients with CSME
      had their glycosylated hemoglobin (HbA1c) measured at baseline and 6 months.
      Central foveal thickness (CFT) and best-corrected visual acuity (BCVA) in logMAR
      were measured at baseline, 3 months, and 6 months. Therapy included laser and
      intravitreal bevacizumab. HbA1c was graded as G1 <7%, G23 7%-7.9%, G3 8%-8.9%, G4
      >9%. Results. Fifty-two eyes were included with mean logMAR BCVA and CFT as
      follows: baseline 0.75 and 423+/-106 um; 3 months 0.47 and 293+/-69 um; and 6
      months 0.48 and 324+/-76 um. Mean HbA1c was 8.13% and 7.43% at baseline and 6
      months, respectively. There was no statistically significant difference between
      baseline and 6 months HbA1c groups and logMAR BCVAs and CFTs at baseline, 3
      months, and 6 months. However, there were positive correlations between baseline
      HbA1c levels and each of baseline logMAR BCVA (p=0.024), baseline CFT (p<0.001),
      and 6-month logMAR BCVA (p=0.007). Improved HbA1c by 6 months did not show any
      correlation with logMAR BCVA and CFT at 6 months. Conclusions. Lower HbA1c
      appeared to be correlated with better visual acuity and lower CFT values at
      baseline, and also correlated with significantly better vision and
      nonsignificantly thinner CFT with therapy at 6 months.

PMID- 22653763
TI  - Cultural adaptation of the difficulties in emotion regulation scale: reliability
      and validity of an Italian version.
AB  - OBJECTIVE: The aim of this study was to evaluate the reliability and validity of
      an Italian version of the Difficulties in Emotion Regulation Scale (DERS; Gratz &
      Roemer, 2004). METHOD: Three studies were completed. First, factorial structure,
      internal consistency, and concurrent validity of our Italian version of the DERS
      were examined with a sample of 323 students (77% female; mean age 25.6). Second,
      test-retest analyses were completed using a different sample of 61 students (80%
      female; mean age 24.7). Third, the scores produced by a small clinical sample of
      participants (N = 38; mean age = 24.2) affected by anorexia, binge eating
      disorder, or bulimia were compared to those of an age-matched, nonclinical female
      sample (N = 38; mean age = 24.7). RESULTS: The factorial structure replicated
      quite well the six-factor structure proposed by Gratz and Roemer. The internal
      consistency and test-retest reliability were adequate and comparable to previous
      findings. The validity was good, as indicated by both the concurrent validity
      analysis and the clinical-nonclinical sample comparison. CONCLUSIONS: These
      studies provide further support for the multidimensional model of emotion
      regulation postulated by Gratz and Roemer and strengthen the rationale for cross
      cultural utilization of the DERS.

PMID- 22653764
TI  - Evidence for a dissociative subtype of PTSD by latent profile and confirmatory
      factor analyses in a civilian sample.
AB  - BACKGROUND: Dissociative symptoms are increasingly recognized in individuals with
      posttraumatic stress disorder (PTSD). The aim of this study was to investigate
      the prevalence of derealization and depersonalization symptoms via latent profile
      analyses (LPAs) in a civilian PTSD sample and examine the relationship between
      PTSD and dissociative symptoms via factor analytic methods. METHODS: A civilian
      sample of individuals with PTSD predominantly related to childhood abuse (n =
      134) completed a diagnostic interview for PTSD and comorbid psychiatric
      disorders. LPAs and confirmatory factor analyses (CFAs) were performed on the
      severity scores for PTSD, derealization, and depersonalization symptoms. RESULTS:
      LPAs extracted three groups, one of which was uniquely characterized by high
      derealization and depersonalization symptoms, and accounted for 25% of the
      sample. Individuals in the dissociative subgroup also showed a higher number of
      comorbid Axis I disorders and a more significant history of childhood abuse and
      neglect. CFAs suggested the acceptance of a five factor solution in which
      dissociative symptoms are distinct from but correlate significantly with the core
      PTSD symptom clusters. CONCLUSIONS: The results from LPAs and CFAs are concordant
      with the concept of a dissociative subtype in patients with PTSD and suggest that
      symptoms of derealization-depersonalization and the core symptoms of PTSD are
      positively correlated. Thought should be given to including a dissociative
      subtype of PTSD in the DSM-5.

PMID- 22653765
TI  - Home mechanical ventilation in Australia and New Zealand.
AB  - This study aims to describe the pattern of home mechanical ventilation (HMV)
      usage in Australia and New Zealand. 34 centres providing HMV in the region were
      identified and asked to complete a questionnaire regarding centre demographics,
      patient diagnoses, HMV equipment and settings, staffing levels and methods
      employed to implement and follow-up therapy. 28 (82%) centres responded,
      providing data on 2,725 patients. The minimum prevalence of HMV usage was 9.9
      patients per 100,000 population in Australia and 12.0 patients per 100,000
      population in New Zealand. Variation existed across Australian states (range 4-13
      patients per 100,000 population) correlating with population density (r=0.82;
      p<0.05). The commonest indications for treatment were obesity hypoventilation
      syndrome (OHS) (31%) and neuromuscular disease (NMD) (30%). OHS was more likely
      to be treated in New Zealand, in smaller, newer centres, whilst NMD was more
      likely to be treated in Australia, in larger, older centres. Chronic obstructive
      pulmonary disease was an uncommon indication (8.0%). No consensus on indications
      for commencing treatment was found. In conclusion, the prevalence of HMV usage
      varies across Australia and New Zealand according to centre location, size and
      experience. These findings can assist HMV service planning locally and highlight
      trends in usage that may be relevant in other countries.

PMID- 22653766
TI  - A trial of beclomethasone/formoterol in COPD using EXACT-PRO to measure
      exacerbations.
AB  - Combination inhalers containing corticosteroids and long-acting beta-agonists are
      used to reduce exacerbation rates in patients with severe chronic obstructive
      pulmonary disease (COPD). The FORWARD (Foster 48-week Trial to Reduce
      Exacerbations in COPD) clinical trial in severe COPD patients is a comparison of
      extrafine beclomethasone dipropionate and formoterol in a combination inhaler
      with extrafine formoterol; the co-primary end-points are exacerbation rates over
      48 weeks and improvement in forced expiratory volume in 1 s over 12 weeks. The
      traditional physician diagnosis of exacerbations is a co-primary outcome, and the
      Exacerbations of Chronic Pulmonary Disease Tool (EXACT) means of collecting
      patient-reported outcome data are also being used to enhance the detection of
      exacerbation events. EXACT data are being collected using a novel application of
      a digital platform technology. FORWARD is therefore expected to provide
      information on the ability of EXACT to detect and measure exacerbations in a
      large clinical trial setting. The study design of FORWARD is described in this
      article.

PMID- 22653767
TI  - Lung function from infancy to preschool in a cohort of children with cystic
      fibrosis.
AB  - This study aimed to describe lung function in a cohort of children with cystic
      fibrosis (CF) who underwent infant pulmonary function tests (IPFTs) and preschool
      spirometry. Children performed up to four IPFTs (raised volume rapid thoracic
      compression technique) over 1 yr and five preschool spirometry tests over up to 2
      yrs during participation in prospective, multicentre studies of infant and
      preschool lung function. All lung function data were reviewed centrally for
      measurement acceptability. 45 children had 252 acceptable measurements (137 IPFTs
      and 115 preschool spirometries) at ages 0.3-6.5 yrs. The median number of
      measurements per participant was 6 (range 3-9). Recent Pseudomonas aeruginosa
      infection was associated with 5.1% (95% CI 0.01-9.9%) lower forced expiratory
      volume in 0.5 s (FEV(0.5)) and 16.4% (95% CI 7.0-24.9%) lower forced expiratory
      flow at 25-25% of forced vital capacity (FEF(25-75%)), after adjustment for
      length, test type and centre. Recent cough was associated with 5.7% (95% CI 1.1
      10.1%) lower FEV(0.5) and 10.1% (95% CI 0.6-18.7%) lower FEF(25-75%). Even after
      accounting for infection status, cough, sex, length, test type and centre, there
      was significant inter-individual variability in lung function (p<0.01 for each of
      FEV(0.5), FEF(25-75%) and forced vital capacity). Recent P. aeruginosa infection
      and cough are associated with lower lung function in children with CF.
      Significant inter-individual variability in lung function remains to be
      explained.

PMID- 22653768
TI  - Early detection of asthma exacerbations by using action points in self-management
      plans.
AB  - Our aim was to validate optimal action points in written action plans for early
      detection of asthma exacerbations. We analysed daily symptoms and morning peak
      expiratory flows (PEFs) from two previous studies. Potential action points were
      based on analysis of symptom scores (standard deviations) percentage of personal
      best PEF, PEF variability in relation to a run-in period or combinations of these
      measures. Sensitivity and specificity for predicting exacerbations were obtained
      for each action point. The numbers needed to treat to prevent one exacerbation
      and the time interval between reaching action point criteria and the start of the
      exacerbation were calculated. Based on these parameters, the optimal action
      points for symptoms, PEF and PEF plus symptoms were determined, and their
      performance compared with published guidelines' action points. The optimal action
      points were, for symptoms, statistical variability (standard deviations) and, for
      PEF, <70% of personal best. The combination of PEF plus symptoms performed best,
      with improved specificity and earlier detection. The main benefits associated
      with using these action points was to reduce false positive rates for detecting
      exacerbations. Early detection of asthma exacerbations can be improved using a
      composite action point comprising symptoms and PEF measurements over 1 week.

PMID- 22653769
TI  - Barriers to an early switch from intravenous to oral antibiotic therapy in
      hospitalised patients with CAP.
AB  - Do physicians apply an early-switch strategy (from intravenous to oral
      antibiotics) in clinically stable patients hospitalised with community-acquired
      pneumonia (CAP)? If not, why not? In a multicentre prospective cohort study,
      adult patients admitted for i.v. CAP treatment were included. On day 3 of
      antibiotic treatment, clinical stability was assessed and treating resident
      physicians were interviewed on their switch strategies. Additionally, treating
      physicians were interviewed to evaluate their knowledge of and adherence to
      guideline advice. 149 (92%) out of 162 patients were included and 97 (91%) out of
      107 physicians were interviewed. A switch to oral antibiotics was possible in 68
      (46%) out of 149 patients on day 3 of treatment but not performed in 27 (40%) out
      of 68. Patient factors delaying the switch were high CURB-65 (confusion of new
      onset, urea >7 mmol . L(-1), respiratory rate of >= 30 breaths . min(-1), blood
      pressure <90 mmHg or diastolic blood pressure <= 60 mmHg, and age >= 65 yrs)
      score (on admission) (p=0.04) and oxygen treatment (p=0.04), high temperature
      (p=0.00) and high respiration rate (p=0.04) (day 3). Physicians' barriers to an
      early switch in clinically stable patients included misconceptions (26 (55%) out
      of 47), practical considerations (13 (28%) out of 47) and organisational factors
      (eight (17%) out of 47). Strikingly, 91 (94%) out of 97 interviewed physicians
      were not aware of guideline advice. The switch from i.v. to oral antibiotics is
      often unnecessarily delayed in patients hospitalised with CAP due to different
      types of barriers.

PMID- 22653770
TI  - PPAR ligands decrease human airway smooth muscle cell migration and extracellular
      matrix synthesis.
AB  - Airway smooth muscle cells produce extracellular matrix proteins, which in turn
      can promote smooth muscle survival, proliferation and migration. Currently
      available therapies have little effect on airway smooth muscle matrix production
      and migration. Peroxisome proliferator-activated receptor (PPAR) ligands are
      reported to decrease migration and matrix production in various cell lines. In
      this study, we examined the effect of PPAR ligands on human airway smooth muscle
      (HASM) matrix production and migration. PPAR expression was examined by RT-PCR
      and Western blotting. Endogenous PPAR activity was examined by transfecting cells
      with a PPAR response element-luciferase reporter plasmid. We observed that HASM
      cells express PPARalpha, beta and gamma. A six-fold induction of luciferase
      activity was observed by stimulating cells with a pan-agonist, indicating
      endogenous PPAR activity. The PPAR ligands ciglitazone, 15-deoxy-Delta12,14
      prostaglandin J(2) and WY-14643 decreased migration towards platelet-derived
      growth factor receptor. This was not mediated by inhibiting Akt phosphorylation
      or promoting PTEN activity, but partly through cyclooxygenase-2 induction and
      prostaglandin E(2) production that increased cyclic AMP levels in the cells. All
      three ligands also caused an inhibition of collagen and fibronectin secretion by
      cultured smooth muscle cells. We conclude that PPAR ligands decrease HASM
      migration and matrix production and are, therefore, potentially useful for
      modulating airway remodelling.

PMID- 22653771
TI  - General and abdominal obesity and incident asthma in adults: the HUNT study.
AB  - Measures of body mass index (BMI) and waist circumference define general obesity
      and abdominal obesity respectively. While high BMI has been established as a risk
      factor for asthma in adults, waist circumference has seldom been investigated. To
      determine the association between BMI, waist circumference and incident asthma in
      adults, we conducted a prospective study (n=23,245) in a population living in
      Nord-Trondelag, Norway in 1995-2008. Baseline BMI and waist circumference were
      measured and categorised as general obesity (BMI >=30.0 kg.m(2)) and abdominal
      obesity (waist circumference >=88 cm in females and >=102 cm in males). Incident
      asthma was self-reported new-onset cases during an 11-yr follow-up period. Odds
      ratios for asthma associated with obesity were calculated using multivariable
      logistic regression. General obesity was a risk factor for asthma in females (OR
      1.96, 95% CI 1.52-2.52) and males (OR 1.84, 95% CI 1.30-2.59). In females, after
      additional adjustment for BMI, abdominal obesity remained a risk factor for
      asthma development (OR 1.46, 95% CI 1.04-2.05). Abdominal obesity seems to
      increase the risk of incident asthma in females in addition to BMI, indicating
      that using both measures of BMI and waist circumference in females may be a
      superior clinical assessment for asthma risk than any measure alone.

PMID- 22653772
TI  - Minimum package for cross-border TB control and care in the WHO European region:
      a Wolfheze consensus statement.
AB  - The World Health Organization (WHO) European region estimates that more than
      400,000 tuberculosis (TB) cases occur in Europe, a large proportion of them among
      migrants. A coordinated public health mechanism to guarantee TB prevention,
      diagnosis, treatment and care across borders is not in place. A consensus paper
      describing the minimum package of cross-border TB control and care was prepared
      by a task force following a literature review, and with input from the national
      TB control programme managers of the WHO European region and the Wolfheze 2011
      conference. A literature review focused on the subject of TB in migrants was
      carried out, selecting documents published during the 11-yr period 2001-2011.
      Several issues were identified in cross-border TB control and care, varying from
      the limited access to early TB diagnosis, to the lack of continuity of care and
      information during migration, and the availability of, and access to, health
      services in the new country. The recommended minimum package addresses the
      current shortcomings and intends to improve the situation by covering several
      areas: political commitment (including the implementation of a legal framework
      for TB cross-border collaboration), financial mechanisms and adequate health
      service delivery (prevention, infection control, contact management, diagnosis
      and treatment, and psychosocial support).

PMID- 22653773
TI  - Efficacy, safety and pharmacokinetics of bosentan in portopulmonary hypertension.
AB  - Data on treatment of patients with portopulmonary hypertension (PoPH) are
      limited, as they are usually excluded from randomised controlled trials with
      pulmonary arterial hypertension (PAH)-specific therapies. This study investigated
      the short- and long-term efficacy/safety of bosentan in these patients, as well
      as its pharmacokinetics. All 34 consecutive patients with PoPH treated with first
      line bosentan (December 2002 to July 2009) were retrospectively evaluated.
      Assessments included the New York Heart Association functional class (NYHA FC),
      blood tests, haemodynamics, 6-min walk distance (6MWD) and event-free status. The
      pharmacokinetics of bosentan in five patients with Child-Pugh (C-P) class B
      cirrhosis were compared with idiopathic PAH patients. Significant improvements
      from baseline were observed in NYHA FC, 6 MWD and haemodynamics, and were largely
      maintained during follow-up. Patients with C-P class B cirrhosis (n=9) had
      significantly larger haemodynamic improvement after mean +/- SD 5 +/- 2 months.
      Mean follow-up time was 43 +/- 19 months; four patients died and seven patients
      had significant elevation of liver enzymes (annual rate 5.5%). Plasma
      concentrations of bosentan were higher in patients with C-P class B cirrhosis
      than those observed in idiopathic PAH. These data confirm the benefit of bosentan
      treatment for patients with PoPH. Haemodynamic improvements were particularly
      pronounced in patients with more severe cirrhosis. The safety profile of bosentan
      was consistent with previous studies.

PMID- 22653775
TI  - Lung cancer risk and solid fuel smoke exposure: a systematic review and meta
      analysis.
AB  - The aim of this systematic review was to quantify the impact of biomass fuel and
      coal use on lung cancer and to explore reasons for heterogeneity in the reported
      effect sizes. A systematic review of primary studies reporting the relationship
      between solid fuel use and lung cancer was carried out, based on pre-defined
      criteria. Studies that dealt with confounding factors were used in the meta
      analysis. Fuel types, smoking, country, cancer cell type and sex were considered
      in sub-group analyses. Publication bias and heterogeneity were estimated. The
      pooled effect estimate for coal smoke as a lung carcinogen (OR 1.82, 95% CI 1.60
      2.06) was greater than that from biomass smoke (OR 1.50, 95% CI 1.17-1.94). The
      risk of lung cancer from solid fuel use was greater in females (OR 1.81, 95% CI
      1.54-2.12) compared to males (OR 1.16, 95% CI 0.79-1.69). The pooled effect
      estimates were 2.33 (95% CI 1.72-3.17) for adenocarcinoma, 3.58 (1.58-8.12) for
      squamous cell carcinoma and 1.57 (1.38-1.80) for tumours of unspecified cell
      type. These findings suggest that in-home burning of both coal and biomass is
      consistently associated with an increased risk of lung cancer.

PMID- 22653774
TI  - Protecting the tuberculosis drug pipeline: stating the case for the rational use
      of fluoroquinolones.
AB  - The use of fluoroquinolones (FQs) to treat lower respiratory tract infections
      (LTRI) other than tuberculosis (TB) allows selection of FQ-resistant TB when TB
      is misdiagnosed. This study maps national guidelines on the use of FQs for LRTI
      in Europe and determines the risk of FQ-resistant TB upon FQ treatment before TB
      diagnosis. A questionnaire was developed to map existing national LRTI and
      community-acquired pneumonia (CAP) guidelines. A systematic review and meta
      analysis were performed to determine the risk of FQ-resistant TB if prescribed
      FQs prior to TB diagnosis. 15 (80%) out of 24 responding European Respiratory
      Society national delegates reported having national LRTI management guidelines,
      seven including recommendations on FQ use and one recommending FQs as the first
      choice drug. 18 out of 24 countries had national CAP management guidelines, two
      recommending FQ as the drug of choice. Six studies investigating FQ exposure and
      the risk of FQ-resistant TB were analysed. TB patients had a three-fold higher
      risk of having FQ-resistant TB when prescribed FQs before TB diagnosis, compared
      to non FQ-exposed patients (OR 2.81, 95% CI 1.47-5.39). Although the majority of
      European countries hold national LRTI/CAP guidelines, our results suggest that a
      risk of developing FQ resistance exists. Further strengthening of, and adherence
      to, guidelines is needed to ensure rational use of FQs.

PMID- 22653776
TI  - TLR9- and Src-dependent expression of Krueppel-like factor 4 controls interleukin
      10 expression in pneumonia.
AB  - The release of potent pro-inflammatory mediators is crucial to mounting an
      efficient host response during infection. However, excessive inflammation may
      lead to deleterious tissue damage. This is highlighted in severe pneumococcal
      pneumonia, in which the delicate balance between a robust inflammatory response
      necessary to kill pneumococci and the loss of organ function determines the
      outcome of the disease. We assessed the regulation of the potent anti
      inflammatory cytokine interleukin (IL)-10 in pneumococcal infection via Western
      blot, ELISA and chromatin immunoprecipitation analysis. Streptococcus pneumoniae
      induced IL-10 expression in mouse lungs and human lung epithelial cells.
      Pneumococcal infection resulted in a strong induction of Krueppel-like factor
      (KLF)4 expression in vivo and in vitro. The induction of both IL-10 and KLF4 is
      mediated by a pathway involving bacterial DNA, Toll-like receptor (TLR)9, MyD88
      and Src kinase. KLF4 is recruited to the il10 promoter, and small-interfering RNA
      mediated knockdown of KLF4 expression blocked IL-10 expression during
      pneumococcal infection. In conclusion, KLF4 is induced in a bacterial DNA-TLR9
      Src-dependent manner and regulates IL-10 expression, linking the detection of
      bacterial DNA by TLR9 to the control of an inflammatory response.

PMID- 22653778
TI  - Bradykinin enhances cell migration in human prostate cancer cells through B2
      receptor/PKCdelta/c-Src dependent signaling pathway.
AB  - BACKGROUND: Prostate cancer is the most commonly diagnosed malignancy in men and
      shows a predilection for metastasis to the bone. Bradykinin (BK) is an
      inflammatory mediator, and shows elevated levels in regions of severe injury and
      inflammatory diseases. The aim of this study was to investigate whether
      Bradykinin is associated with migration of prostate cancer cells. METHODS: Cancer
      cells migration activity was examined using the Transwell assay. The c-Src and
      PKCdelta phosphorylation was examined by using Western blot method. The qPCR was
      used to examine the mRNA expression of metalloproteinase. A transient
      transfection protocol was used to examine NF-kappaB activity. RESULTS: We found
      that bradykinin increased the chemomigration and the expression of MMP-9 of human
      prostate cancer cells. Bradykinin-mediated chemomigration and metalloproteinase
      expression was attenuated by PKCdelta inhibitor (rottlerin), PKCdelta siRNA, c
      Src inhibitor (PP2) and c-Src mutant. Activations of PKCdelta, c-Src and NF
      kappaB pathways after bradykinin treatment was demonstrated, and bradykinin
      induced expression of metalloproteinase and chemomigration activity was inhibited
      by the specific inhibitor and mutant of PKCdelta, c-Src, and NF-kappaB cascades.
      CONCLUSIONS: This study showed for the first time that the bradykinin mediates
      migration of human prostate cancer cells. One of the mechanisms underlying
      bradykinin directed migration was transcriptional up-regulation of MMP-9 and
      activation of B2 receptor, PKCdelta, c-Src, and NF-kappaB pathways.

PMID- 22653779
TI  - Expression of olfactory-type cyclic nucleotide-gated channels in rat cortical
      astrocytes.
AB  - Cyclic nucleotide-gated (CNG) channels are nonselective cation channels activated
      by cyclic AMP (cAMP) or cyclic GMP (cGMP). They were originally identified in
      retinal and olfactory receptors, but evidence has also emerged for their
      expression in several mammalian brain areas. Because cGMP and cAMP control
      important aspects of glial cell physiology, we wondered whether CNG channels are
      expressed in astrocytes, the most functionally relevant glial cells in the CNS.
      Immunoblot and immunofluorescence experiments demonstrated expression of the CNG
      channel olfactory-type A subunit, CNGA2, in cultured rat cortical astrocytes. In
      patch-clamp experiments, currents elicited in these cells by voltage ramps from 
      100 to +100 mV in the presence of the cGMP analogue, dB-cGMP, were significantly
      reduced by the CNG channel blockers, L-cis-diltiazem (LCD) and Cd(2+) . The
      reversal potentials of the LCD- and Cd(2+) -sensitive currents were more positive
      than that of K(+) , as expected for a mixed cation current. Noninactivating,
      voltage-independent currents were also elicited by extracellular application of
      the membrane permeant cGMP analogue, 8-Br-cGMP. These effects were blocked by LCD
      and were mimicked by natriuretic peptide receptor activation and inhibition of
      phosphodiesterase activity. Voltage-independent, LCD-sensitive currents were also
      elicited by 8-Br-cGMP in astrocytes of hippocampal and neocortical brain slices.
      Immunohistochemistry confirmed a broad distribution of CNG channels in astrocytes
      of the rat forebrain, midbrain, and hindbrain. These findings suggest that CNG
      channels are downstream targets of cyclic nucleotides in astrocytes, and they may
      be involved in the glial-mediated regulation of CNS functions under physiological
      and pathological conditions.

PMID- 22653780
TI  - OMIP-012: Phenotypic and numeric determination of human leukocyte reconstitution
      in humanized mice.

PMID- 22653781
TI  - Risk and protective behaviours for residential carbon monoxide poisoning.
AB  - BACKGROUND: Unintentional, non-fire-related carbon monoxide (CO) poisoning is a
      leading cause of poisoning death and injury in the USA. Residential poisonings
      caused by faulty furnaces are the most common type of CO exposure. However, these
      poisonings are largely preventable with annual furnace inspections and CO alarm
      installation. OBJECTIVE: This study aimed to identify the knowledge, attitudes
      and beliefs that might lead consumers to adopt these protective behaviours.
      METHODS: In August 2009, four focus groups (n=29) were conducted with homeowners
      in Chicago, Illinois, USA, to identify the knowledge, attitudes and beliefs that
      lead consumers to adopt risk and protective behaviours. Discussions were
      transcribed and the findings were analysed using an ordered meta-matrix. RESULTS:
      Focus group participants were aware of CO poisoning and supported the idea of
      regular furnace inspections. However, few participants consistently scheduled
      professional inspections for fear of costly repairs and unscrupulous contractors.
      Participants often owned CO alarms, but many did not locate them properly, nor
      maintain them. Some participants confused CO and natural gas and were unsure how
      to react if a CO alarm sounds. Participants stated that incentives, such as
      discounts and inspector selection tips, would make them more likely to schedule
      furnace inspections. Participants also identified trustworthy sources for CO
      education, including realtors, fire departments, home insurance agents and local
      media outlets. CONCLUSIONS: Participants' residential CO risk behaviours are not
      random but driven by underlying knowledge, attitudes and beliefs. Correcting
      misperceptions, providing incentives and partnering with trustworthy sources
      might encourage greater consumer adoption of protective behaviours.

PMID- 22653782
TI  - You are the weakest link, goodbye (to physical inactivity!): a comment on Irwin
      et al.

PMID- 22653785
TI  - Aryl hydrocarbon receptor controls regulatory CD4+ T cell function.
AB  - The ligand activated transcription factor aryl hydrocarbon receptor (AhR) has
      been studied for many decades in toxicology as the ligand for the environmental
      contaminant dioxin. However, AhR has recently emerged as a critical physiological
      regulator of immune responses affecting both innate and adaptive systems, and
      several AhR ligands with different pharmacological profiles have recently been
      studied. The current review discusses new insights into the role of AhR
      signalling and AhR ligands on the regulation of the immune system, with a focus
      on regulatory T cells which maintain immune tolerance. Notably, AhR is expressed
      and modulates the development of two induced regulatory CD4+ T cell subsets, the
      forkhead box P3-positive (Foxp3+) regulatory T cells (iTreg) and the IL-10
      secreting type 1 regulatory T (T(R)1) cells, through different signalling
      pathways. We will finally discuss how AhR ligands could be exploited to alleviate
      human autoimmune diseases. Clearly, drugs targeted against AhR should promote the
      development of new strategies to fight against autoimmune diseases.

PMID- 22653783
TI  - Sildenafil reduces respiratory muscle weakness and fibrosis in the mdx mouse
      model of Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy
      caused by mutations in the dystrophin gene. Loss of dystrophin initiates a
      progressive decline in skeletal muscle integrity and contractile capacity which
      weakens respiratory muscles including the diaphragm, culminating in respiratory
      failure, the leading cause of morbidity and mortality in DMD patients. At
      present, corticosteroid treatment is the primary pharmacological intervention in
      DMD, but has limited efficacy and adverse side effects. Thus, there is an urgent
      need for new safe, cost-effective, and rapidly implementable treatments that slow
      disease progression. One promising new approach is the amplification of nitric
      oxide-cyclic guanosine monophosphate (NO-cGMP) signalling pathways with
      phosphodiesterase 5 (PDE5) inhibitors. PDE5 inhibitors serve to amplify NO
      signalling that is attenuated in many neuromuscular diseases including DMD. We
      report here that a 14-week treatment of the mdx mouse model of DMD with the PDE5
      inhibitor sildenafil (Viagra((r)), Revatio((r))) significantly reduced mdx
      diaphragm muscle weakness without impacting fatigue resistance. In addition to
      enhancing respiratory muscle contractility, sildenafil also promoted normal
      extracellular matrix organization. PDE5 inhibition slowed the establishment of
      mdx diaphragm fibrosis and reduced matrix metalloproteinase-13 (MMP-13)
      expression. Sildenafil also normalized the expression of the pro-fibrotic (and
      pro-inflammatory) cytokine tumour necrosis factor alpha (TNFalpha). Sildenafil
      treated mdx diaphragms accumulated significantly less Evans Blue tracer dye than
      untreated controls, which is also indicative of improved diaphragm muscle health.
      We conclude that sildenafil-mediated PDE5 inhibition significantly reduces
      diaphragm respiratory muscle dysfunction and pathology in the mdx mouse model of
      Duchenne muscular dystrophy. This study provides new insights into the
      therapeutic utility of targeting defects in NO-cGMP signalling with PDE5
      inhibitors in dystrophin-deficient muscle.

PMID- 22653786
TI  - Maximizing modern distribution of complex anatomical spatial information: 3D
      reconstruction and rapid prototype production of anatomical corrosion casts of
      human specimens.
AB  - Anatomical corrosion casts of human specimens are useful teaching aids. However,
      their use is limited due to ethical dilemmas associated with their production,
      their lack of perfect reproducibility, and their consumption of original
      specimens in the process of casting. In this study, new approaches with modern
      distribution of complex anatomical spatial information were explored to overcome
      these limitations through the digitalization of anatomical casts of human
      specimens through three-dimensional (3D) reconstruction, rapid prototype
      production, and Web-based 3D atlas construction. The corrosion cast of a lung,
      along with its associated arteries, veins, trachea, and bronchial tree was CT
      scanned, and the data was then processed by Mimics software. Data from the lung
      casts were then reconstructed into 3D models using a hybrid method, utilizing
      both "image threshold" and "region growing." The fine structures of the bronchial
      tree, arterial, and venous network of the lung were clearly displayed and
      demonstrated their distinct relationships. The multiple divisions of bronchi and
      bronchopulmonary segments were identified. The 3D models were then uploaded into
      a rapid prototype 3D printer to physically duplicate the cast. The physically
      duplicated model of the lung was rescanned by CT and reconstructed to detect its
      production accuracy. Gross observation and accuracy detection were used to
      evaluate the duplication and few differences were found. Finally, Virtual Reality
      Modeling Language (VRML) was used to edit the 3D casting models to construct a
      Web-based 3D atlas accessible through Internet Explorer with 3D display and
      annotation functions.

PMID- 22653784
TI  - MicroRNAs are universal regulators of differentiation, activation, and
      polarization of microglia and macrophages in normal and diseased CNS.
AB  - MicroRNAs (miRNAs) are a class of small (~22 nucleotides) noncoding RNAs involved
      in the regulation of gene expression at the post-translational level. It is
      estimated that 30-90% of human genes are regulated by miRNAs, which makes these
      molecules of great importance for cell growth, activation, and differentiation.
      Microglia is CNS-resident cells of a myeloid lineage that play an important role
      in immune surveillance and are actively involved in many neurologic pathologies.
      Although the exact origin of microglia remains enigmatic, it is established that
      primitive macrophages from a yolk sac populate the brain and spinal cord in
      normal conditions throughout development. During various pathological events such
      as neuroinflammation, bone marrow derived myeloid cells also migrate into the
      CNS. Within the CNS, both primitive macrophages from the yolk sac and bone marrow
      derived myeloid cells acquire a specific phenotype upon interaction with other
      cell types within the CNS microenvironment. The factors that drive
      differentiation of progenitors into microglia and control the state of activation
      of microglia and bone marrow-derived myeloid cells within the CNS are not well
      understood. In this review we will summarize the role of miRNAs during activation
      and differentiation of myeloid cells. The role of miR-124 in the adaptation of
      microglia and macrophages to the CNS microenvironment will be further discussed.
      We will also summarize the role of miRNAs as modulators of activation of
      microglia and microphages. Finally, we will describe the role of miR-155 and miR
      124 in the polarization of macrophages towards classically and alternatively
      activated phenotypes.

PMID- 22653787
TI  - Role of glyoxalase I in the proliferation and apoptosis control of human LNCaP
      and PC3 prostate cancer cells.
AB  - BACKGROUND: Glyoxalase I (GLOI) detoxifies reactive dicarbonyls, as methylglyoxal
      (MG) that, directly or through the formation of MG-derived adducts, is a growth
      inhibitor and apoptosis inducer. GLOI has been considered a general marker of
      cell proliferation, but a direct link between the two has yet to be demonstrated.
      The aim of the present work was to clarify whether GLOI was involved in the
      proliferation control of LNCaP and PC3 human prostate cancer cells or might play
      a different role in the growth regulation of these cells. METHODS: RNA
      interference was used to study the role of GLOI in cell proliferation or
      apoptosis. Cell proliferation was evaluated by [3H]thymidine incorporation assay
      and flow cytometry, that was also used to analyze apoptosis. Real-time TaqMan
      polymerase chain reaction and spectrophotometric analyses were used to study
      transcript levels or specific activity, respectively. Proteins levels were
      analyzed by Western blot. MG was measured by high-performance liquid
      chromatography. RESULTS: We found that GLOI is not implicated in the
      proliferation control of LNCaP and PC3 cells but plays a role in the apoptosis of
      invasive prostate cancer PC3 cells, through a mechanism involving a specific MG
      adduct and NF-kB signaling pathway. CONCLUSIONS: Our data represent the first
      systematic demonstration that GLOI cannot be considered a general marker of cell
      proliferation and that acts as a pro-survival factor in invasive PC3 cells by
      elusing apoptosis. GLOI may be involved in prostate cancer progression, via the
      control of key molecules in the mitochondrial apoptotic mechanism, through NF-kB
      signaling pathway.

PMID- 22653788
TI  - Expanding the zebrafish embryo proteome using multiple fractionation approaches
      and tandem mass spectrometry.
AB  - The proteome of zebrafish, Danio rerio, embryos has not been studied in great
      detail mainly due to the presence of high abundance yolk proteins in embryos.
      Here we report the highest number of the zebrafish embryo proteins identified so
      far to our knowledge, through a combination of a protein-level fractionation
      approach (1D SDS-PAGE) and two different peptide-level fractionation approaches
      (IEF and strong anion exchange (SAX)) of deyolked zebrafish embryos followed by
      LC-MS/MS. We detected 5267 proteins in total of which 3464 proteins were
      identified with at least two peptides (less than 1% peptide false discovery
      rate). The analysis of proteome coverage from each method showed that 56% of
      detected proteins were common to all approaches and 95% of the detected proteome
      was obtained from 1D SDS-PAGE approach alone. Bioinformatics analysis of the
      detected proteome demonstrated that nucleocytoplasmic transport (biological
      process) and ribosomal proteins (cellular component) were the most over
      represented proteins, whereas cell-cell signaling (biological process) and
      extracellular space proteins (cellular component) were the most under-represented
      proteins in the identified proteome.

PMID- 22653789
TI  - Simple sets for digital microphotography used and tested in the study of
      microorganisms.
AB  - Four simple sets for digital microphotography are described that have been tested
      with the Carl Zeiss Jena, Meopta Prague, Lambda Prague, and LOMO Sankt Petersburg
      microscopes and with DSLR Nikon D 70 and Nikon D 300 cameras. They permit precise
      image focusing in the camera using a prism Zeiss. The sets make use of commonly
      available extensions Zeiss, Praktica and reductions Nikon-Praktica manufactured
      by ROWI (without a lens) or HAMA (with a lens). An extension has further been
      designed and manufactured for connecting the DSLR Nikon D 300 camera fitted with
      the HAMA reduction (only with a lens) and a focusing extensible prism with Zeiss
      Jena light measurement. It permits a precise image focusing of low light
      intensity objects (autofluorescence or low-contrast or moving objects when using
      positive or negative phase contrast). The sets are applicable to all microscopes
      constructed according to German DIN industrial standards.

PMID- 22653790
TI  - Molecular diversity analysis of Rhizoctonia solani isolates infecting various
      pulse crops in different agro-ecological regions of India.
AB  - Genetic diversity of 89 isolates of Rhizoctonia solani isolated from different
      pulse crops representing 21 states from 16 agro-ecological regions of India, 49
      morphological, and 7 anastomosis groups (AGs) was analyzed using 12 universal
      rice primers (URPs), 22 random amplified polymorphic DNA (RAPD), and 23 inter
      simple sequence repeats (ISSR) markers. Both URPs and RAPD markers provided 100 %
      polymorphism with the bands ranging from 0.1 to 5 kb in size, whereas ISSR
      markers gave 99.7 % polymorphism with the bands sizes ranging from 0.1 to 3 kb.
      The marker URP 38F followed by URP13R, URP25F, and URP30F, RAPD marker R1
      followed by OPM6, A3 and OPA12 and ISSR3 followed by ISSR1, ISSR4, and ISSR20
      produced the highest number of amplicons. R. solani isolates showed a high level
      of genetic diversity. Unweighted pair group method with an arithmetic average
      (UPGMA) analysis grouped the isolates into 7 major clusters at 35 % genetic
      similarity using the three sets of markers evaluated. In spite of using three
      different types of markers, about 95 % isolates shared common grouping patterns.
      The majority of the isolates representing various AGs were grouped together into
      different sub-clusters using all three types of markers. Molecular groups of the
      isolates did not correspond to agro-ecological regions or states and crops of the
      origin. An attempt was made for the first time in the present study to determine
      the genetic diversity of R. solani populations isolated from different pulse
      crops representing various AGs and agro-ecological regions.

PMID- 22653791
TI  - PET and MRI reveal early evidence of neurodegeneration in spinocerebellar ataxia
      type 17.
AB  - Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominantly inherited
      neurodegenerative disorder presenting with a variable phenotype including ataxia,
      dystonia, chorea, and parkinsonism, as well as cognitive impairment. We evaluated
      morphologic and functional imaging characteristics to elucidate evidence of
      neurodegeneration in SCA17, even in the presymptomatic stage of the disease.
      METHODS: Nine individuals of 3 large SCA17 pedigrees, including 4 presymptomatic
      mutation carriers, underwent cranial 3-dimensional MRI volumetry, as well as
      multitracer PET with (18)F-FDG, (11)C-d-threo-methylphenidate, and (11)C
      raclopride. Healthy subjects showing no signs of a neurologic or psychiatric
      disease served as controls. RESULTS: MRI volumetry revealed atrophy of the
      cerebellum and caudate nucleus in manifesting patients (P = 0.04 and 0.05,
      respectively) and in presymptomatic mutation carriers (P = 0.04 and 0.01,
      respectively). PET demonstrated decreased glucose metabolism in the striatum, as
      well as in the cuneus, cingulum, and parietal lobe, in all SCA17 patients and
      presymptomatic mutation carriers. In addition, PET was closely correlated with
      motor performance as assessed by the Scale for the Assessment and Rating of
      Ataxia (P = 0.037) and Unified Parkinson Disease Rating Scale (P = 0.05) and with
      cognitive function as assessed by the Mini-Mental Status Examination (P = 0.037).
      Furthermore, (11)C-raclopride PET showed impairment of the postsynaptic
      dopaminergic compartment of the putamen and caudate nucleus not only in manifest
      SCA17 patients (P = 0.04 and 0.008, respectively) but also in yet-unaffected
      mutation carriers (P = 0.05 and 0.05, respectively). The degree of postsynaptic
      dopaminergic dysfunction was associated with impairment of motor performance. In
      contrast, significant presynaptic dopaminergic deficits assessed with (11)C-d
      threo-methylphenidate PET were not detected. CONCLUSION: MRI volumetry, as well
      as (11)C-raclopride and (18)F-FDG PET, reveal neuronal dysfunction and
      neurodegeneration even in the presymptomatic stage and may serve as markers for
      disease activity in upcoming interventional trials on SCA17.

PMID- 22653792
TI  - Accurate differentiation of recurrent gliomas from radiation injury by kinetic
      analysis of alpha-11C-methyl-L-tryptophan PET.
AB  - PET of amino acid transport and metabolism may be more accurate than conventional
      neuroimaging in differentiating recurrent gliomas from radiation-induced tissue
      changes. alpha-(11)C-methyl-l-tryptophan ((11)C-AMT) is an amino acid PET tracer
      that is not incorporated into proteins but accumulates in gliomas, mainly because
      of tumoral transport and metabolism via the immunomodulatory kynurenine pathway.
      The aim of this study was to evaluate the usefulness of (11)C-AMT PET
      supplemented by tracer kinetic analysis for distinguishing recurrent gliomas from
      radiation injury. METHODS: Twenty-two (11)C-AMT PET scans were obtained in adult
      patients who presented with a lesion suggestive of tumor recurrence on
      conventional MRI 1-6 y (mean, 3 y) after resection and postsurgical radiation of
      a World Health Organization grade II-IV glioma. Lesional standardized uptake
      values were calculated, as well as lesion-to-contralateral cortex ratios and 2
      kinetic (11)C-AMT PET parameters (volume of distribution [VD], characterizing
      tracer transport, and unidirectional uptake rate [K]). Tumor was differentiated
      from radiation-injured tissue by histopathology (n = 13) or 1-y clinical and MRI
      follow-up (n = 9). Accuracy of tumor detection by PET variables was assessed by
      receiver-operating-characteristic analysis. RESULTS: All (11)C-AMT PET parameters
      were higher in tumors (n = 12) than in radiation injury (n = 10) (P <= 0.012 in
      all comparisons). The lesion-to-cortex K-ratio most accurately identified tumor
      recurrence, with highly significant differences both in the whole group (P <
      0.0001) and in lesions with histologic verification (P = 0.006); the area under
      the receiver-operating-characteristic curve was 0.99. A lesion-to-cortex K-ratio
      threshold of 1.39 (i.e., a 39% increase) correctly differentiated tumors from
      radiation injury in all but 1 case (100% sensitivity and 91% specificity). In
      tumors that were high-grade initially (n = 15), a higher lesion-to-cortex K-ratio
      threshold completely separated recurrent tumors (all K-ratios >= 1.70) from
      radiation injury (all K-ratios < 1.50) (100% sensitivity and specificity).
      CONCLUSION: Kinetic analysis of dynamic (11)C-AMT PET images may accurately
      differentiate between recurrent World Health Organization grade II-IV
      infiltrating gliomas and radiation injury. Separation of unidirectional uptake
      rates from transport can enhance the differentiating accuracy of (11)C-AMT PET.
      Applying the same approach to other amino acid PET tracers might also improve
      their ability to differentiate recurrent gliomas from radiation injury.

PMID- 22653793
TI  - Reception learning and self-discovery learning in histology: students'
      perceptions and their implications for assessing the effectiveness of different
      learning modalities.
AB  - Two questionnaires were used to investigate students' perceptions of their
      motivation to opt for reception learning (RL) or self-discovery learning (SDL) in
      histology and their choices of complementary learning strategies (CLS). The
      results demonstrated that the motivation to attend RL sessions was higher than
      the motivation to attend SDL to gain new knowledge (P < 0.01) and to apply this
      acquired knowledge to diagnosis (P < 0.01), therapy (P < 0.01), and research (P <
      0.05). Students also showed a stronger preference for RL based on motivations
      related to leadership (P < 0.01) and competition (P < 0.01), although the rates
      were very low in both cases (<= 1.9 +/- 1.1). Statistically significant
      differences were found between male and female students for leadership (higher in
      males), responsibility (higher in females), and acquiring new knowledge (higher
      in females only in RL). This study's findings for students' preferred CLS
      strategies suggested a greater need for additional complementary resources after
      RL than after SDL (P < 0.01). In conclusion, RL was associated with a greater
      need for complementary training resources such as textbooks, atlases, the
      internet, audiovisual media, and tutorials, whereas SDL was associated with a
      greater need to orient teaching and training toward medical practice. These
      results suggest the need to reorient both types of learning processes to enhance
      their effectiveness in teaching histology, especially in the case of SDL, which
      should place more emphasis on clinically oriented knowledge.

PMID- 22653794
TI  - Up-regulated expression of sulfatases (SULF1 and SULF2) as prognostic and
      metastasis predictive markers in human gastric cancer.
AB  - Gastric cancer (GC) is the fourth most common cancer worldwide. In spite of the
      mortality incidence associated with GC, no reliable prognostic biomarkers are
      currently available for this malignancy. The sulfatases (or SULFs), SULF1 and
      SULF2, play a critical role in the pathogenesis of a variety of human cancers. We
      sought to evaluate the potential of SULFs as biomarkers for GC. Thirty pairs of
      GC and corresponding normal tissues were analysed for the expression and
      methylation status of SULFs. Furthermore, the functional role of SULF
      overexpression was investigated in GC cell lines and tumour xenograft animal
      models. Lastly, we validated the expression of SULF1 protein in a large cohort of
      450 GC patients. GC tissues showed conspicuously higher expression of SULF1 (p =
      0.0002) and SULF2 (p = 0.001) compared to normal mucosa, which was correlated
      with its promoter hypomethylation. Furthermore, high expression of SULFs caused
      marked acceleration in the growth of xenograft tumours in nude mice. The
      expression of SULF1 protein significantly correlated with higher recurrence rates
      (p = 0.0002) and worse overall survival (p < 0.0001) in GC patients. Multivariate
      analysis revealed that SULF1 is an independent prognostic (p = 0.0123) and lymph
      node metastasis predictive factor (p = 0.0003) in patients with GC. We provide
      novel evidence that hypomethylation of promoter CpG islands within SULF genes
      imparts them with oncogenic potential in GC. Moreover, our data suggest that
      SULF1 may serve as a promising biomarker for patients with GC.

PMID- 22653795
TI  - HIV antibodies and athletes.

PMID- 22653796
TI  - CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on
      experimentally induced inflammation.
AB  - The endocannabinoid anandamide (AEA) is released by macrophages and microglia on
      pathological neuroinflammatory conditions such as multiple sclerosis (MS). CD200
      is a membrane glycoprotein expressed in neurons that suppresses immune activity
      via its receptor (CD200R) mainly located in macrophages/microglia. CD200-CD200R
      interactions contribute to the brain immune privileged status. In this study, we
      show that AEA protects neurons from microglia-induced neurotoxicity via CD200
      CD200R interaction. AEA increases the expression of CD200R1 in LPS/IFN-gamma
      activated microglia through the activation of CB(2) receptors. The
      neuroprotective effect of AEA disappears when microglial cells derive from
      CD200R1(-/-) mice. We also show that engagement of CD200R1 by CD200Fc decreased
      the production of the proinflammatory cytokines IL-1beta and IL-6, but increased
      IL-10 in activated microglia. In the chronic phases of Theiler's virus-induced
      demyelinating disease (TMEV-IDD) the expression of CD200 and CD200R1 was reduced
      in the spinal cord. AEA-treated animals up-regulated the expression of CD200 and
      CD200R1, restoring levels found in sham animals together with increased
      expression of IL-10 and reduced expression of IL-1beta and IL-6. Treated animals
      also improved their motor behavior. Because AEA up-regulated the expression of
      CD200R1 in microglia, but failed to enhance CD200 in neurons we suggest that AEA
      induced up-regulation of CD200 in TMEV-IDD is likely due to IL-10 as this
      cytokine increases CD200 in neurons. Our findings provide a new mechanism of
      action of AEA to limit immune response in the inflamed brain.

PMID- 22653797
TI  - Mapping the invisible hand: a body model of a phantom limb.

PMID- 22653798
TI  - The local-ladder effect: social status and subjective well-being.
AB  - Dozens of studies in different nations have revealed that socioeconomic status
      only weakly predicts an individual's subjective well-being (SWB). These results
      imply that although the pursuit of social status is a fundamental human
      motivation, achieving high status has little impact on one's SWB. However, we
      propose that sociometric status-the respect and admiration one has in face-to
      face groups (e.g., among friends or coworkers)-has a stronger effect on SWB than
      does socioeconomic status. Using correlational, experimental, and longitudinal
      methodologies, four studies found consistent evidence for a local-ladder effect:
      Sociometric status significantly predicted satisfaction with life and the
      experience of positive and negative emotions. Longitudinally, as sociometric
      status rose or fell, SWB rose or fell accordingly. Furthermore, these effects
      were driven by feelings of power and social acceptance. Overall, individuals'
      sociometric status matters more to their SWB than does their socioeconomic
      status.

PMID- 22653799
TI  - Reconstruing intolerance: abstract thinking reduces conservatives' prejudice
      against nonnormative groups.
AB  - Myrdal (1944) described the "American dilemma" as the conflict between abstract
      national values ("liberty and justice for all") and more concrete, everyday
      prejudices. We leveraged construal-level theory to empirically test Myrdal's
      proposition that construal level (abstract vs. concrete) can influence prejudice.
      We measured individual differences in construal level (Study 1) and manipulated
      construal level (Studies 2 and 3); across these three studies, we found that
      adopting an abstract mind-set heightened conservatives' tolerance for groups that
      are perceived as deviating from Judeo-Christian values (gay men, lesbians,
      Muslims, and atheists). Among participants who adopted a concrete mind-set,
      conservatives were less tolerant of these nonnormative groups than liberals were,
      but political orientation did not have a reliable effect on tolerance among
      participants who adopted an abstract mind-set. Attitudes toward racial out-groups
      and dominant groups (e.g., Whites, Christians) were unaffected by construal
      level. In Study 3, we found that the effect of abstract thinking on prejudice was
      mediated by an increase in concerns about fairness.

PMID- 22653800
TI  - Treatment of immune thrombocytopenia with intravenous immunoglobulin and insights
      for other diseases. A historical review.
AB  - Since 1946 the development of fractionation and purification methods of human
      plasma led to biologic immunoglobulin for intravenous use (IVIG). In 1980 a child
      with refractory immune thrombocytopenia (ITP), bleeding and secondary
      hypogammaglobulinaemia due to long term immunosuppressive treatment got IVIG. His
      platelet counts dramatically increased. In 13 consecutive children with ITP, but
      without hypogammaglobulinaemia, similar rapid platelet increases were observed
      and confirmed in a controlled, multicentre study. During the past three decades
      this biologic treatment modality evoked clinical and laboratory research on the
      mechanisms of action and in disorders with similar immune pathogenesis. It was
      recognised that IVIG modulates the disturbed immune response in multiple,
      synergistic ways between the different components of the immune system. Beside
      other immune hematologic disorders other inflammatory and autoimmune diseases,
      mainly in the field of neurology and dermatology, IVIG showed beneficial effects.
      The worldwide consumption of IVIG increased from 300 kg per year in 1980 to 100
      tonnes per year in 2010. Due to the heterogeneity of immunopathological
      mechanisms of autoimmune diseases evidence based indications of IVIG remain rare
      and off label use high. Registries of large numbers of patients and first
      endpoints of defining less heterogenous subgroups in immune related disorders are
      the next steps toward establishment of evidence based IVIG indications.

PMID- 22653802
TI  - Reduction of mental distress in the dissection course by introducing the body
      donor experience through anatomical demonstrations of organ systems.
AB  - The practice of dissection teaches students not only the foundations of
      anatomical knowledge but also encourages the development of professional
      competencies. Yet, the dissection of cadavers in the gross anatomy course can be
      a stress factor for medical students. There are a minor proportion of students
      who demonstrate strong emotional reactions in anticipation of being confronted
      with a cadaver. Therefore, in 2008, the authors implemented a voluntary course
      entitled, "Anatomical demonstrations of organ systems" (AD-OS) in advance of the
      dissection course to ease this psychological burden. The question of whether
      attendees of AD-OS showed less mental distress at the start of the dissection
      course compared with those that had not or only infrequently visited AD-OS was
      addressed. AD-OS attendees assessed their expected mental distress using a five
      point Likert scale before starting the dissection course and a second time at the
      end of their first day, after they had been confronted with a cadaver. AD-OS was
      evaluated as excellent and the majority of students participated actively during
      teaching sessions. Overall, female students showed higher levels of mental
      distress. AD-OS attendees assessed themselves as being less burdened by mental
      distress than members of the control group. Longitudinal analysis revealed that
      students who visited AD-OS showed a marked decrease of their mental distress
      level, comparing prospective and retrospective ratings. This was significantly (P
      < 0.001; Z = -6.061) different from nonattendees or those who visited AD-OS only
      infrequently. AD-OS satisfied its intended teaching goals and proved that a step
      by-step introduction of dissection through anatomical demonstrations helped to
      reduce the mental distress of students. Future studies are planned to measure
      mental distress with objective instruments.

PMID- 22653803
TI  - Site-specific degree of phosphorylation in proteins measured by liquid
      chromatography-electrospray mass spectrometry.
AB  - This review focuses on quantitative protein phosphorylation analysis based on
      coverage of both the phosphorylated and nonphosphorylated forms. In this way,
      site-specific data on the degree of phosphorylation can be measured, generating
      the most detailed level of phosphorylation status analysis of proteins. To
      highlight the experimental challenges in this type of quantitative protein
      phosphorylation analysis, we discuss the typical workflows for mass spectrometry
      based proteomics with a focus on the quantitative analysis of
      peptide/phosphopeptide ratios. We review workflows for measuring site-specific
      degrees of phosphorylation including the label-free approach, differential stable
      isotope labeling of analytes, and methods based on the addition of stable isotope
      labeled peptide/phosphopeptide pairs as internal standards. The discussion also
      includes the determination of phosphopeptide isoform abundance data for multiply
      phosphorylated motifs that contain information about the connectivity of
      phosphorylation events. The review closes with a prospective on the use of intact
      stable isotope labeled proteins as internal standards and a summarizing
      discussion of the typical accuracies of the individual methods.

PMID- 22653801
TI  - Epicardial progenitor cells in cardiac development and regeneration.
AB  - The epicardium forms an epithelial layer on the surface of the heart. It is
      derived from a cluster of mesothelial cells, which is termed the proepicardium.
      The proepicardium gives rise not only to the epicardium but also to epicardium
      derived cells. These cells populate the myocardial wall and differentiate into
      smooth muscle cells, fibroblast, and possibly endothelial cells. In this review,
      the formation of the proepicardium is discussed. Marker genes, suitable to
      identify these cells in the embryo and in the adult, are introduced. Recent
      evidence suggests that the PE is made up of distinct cell populations. These cell
      lineages can be distinguished on the basis of marker gene expression and differ
      in their differentiation potential. The role of the epicardium as a resource for
      cardiac stem cells and its importance in cardiac regeneration is also discussed.

PMID- 22653805
TI  - Comparing the cohort design and the nested case-control design in the presence of
      both time-invariant and time-dependent treatment and competing risks: bias and
      precision.
AB  - PURPOSE: Observational studies using electronic administrative healthcare
      databases are often used to estimate the effects of treatments and exposures.
      Traditionally, a cohort design has been used to estimate these effects, but
      increasingly, studies are using a nested case-control (NCC) design. The relative
      statistical efficiency of these two designs has not been examined in detail.
      METHODS: We used Monte Carlo simulations to compare these two designs in terms of
      the bias and precision of effect estimates. We examined three different settings:
      (A) treatment occurred at baseline, and there was a single outcome of interest;
      (B) treatment was time varying, and there was a single outcome; and C treatment
      occurred at baseline, and there was a secondary event that competed with the
      primary event of interest. Comparisons were made of percentage bias, length of
      95% confidence interval, and mean squared error (MSE) as a combined measure of
      bias and precision. RESULTS: In Setting A, bias was similar between designs, but
      the cohort design was more precise and had a lower MSE in all scenarios. In
      Settings B and C, the cohort design was more precise and had a lower MSE in all
      scenarios. In both Settings B and C, the NCC design tended to result in estimates
      with greater bias compared with the cohort design. CONCLUSIONS: We conclude that
      in a range of settings and scenarios, the cohort design is superior in terms of
      precision and MSE. Copyright (c) 2012 John Wiley & Sons, Ltd.

PMID- 22653804
TI  - Use of mutation profiles to refine the classification of endometrial carcinomas.
AB  - The classification of endometrial carcinomas is based on pathological assessment
      of tumour cell type; the different cell types (endometrioid, serous,
      carcinosarcoma, mixed, undifferentiated, and clear cell) are associated with
      distinct molecular alterations. This current classification system for high-grade
      subtypes, in particular the distinction between high-grade endometrioid (EEC-3)
      and serous carcinomas (ESC), is limited in its reproducibility and prognostic
      abilities. Therefore, a search for specific molecular classifiers to improve
      endometrial carcinoma subclassification is warranted. We performed target
      enrichment sequencing on 393 endometrial carcinomas from two large cohorts,
      sequencing exons from the following nine genes: ARID1A, PPP2R1A, PTEN, PIK3CA,
      KRAS, CTNNB1, TP53, BRAF, and PPP2R5C. Based on this gene panel, each endometrial
      carcinoma subtype shows a distinct mutation profile. EEC-3s have significantly
      different frequencies of PTEN and TP53 mutations when compared to low-grade
      endometrioid carcinomas. ESCs and EEC-3s are distinct subtypes with significantly
      different frequencies of mutations in PTEN, ARID1A, PPP2R1A, TP53, and CTNNB1.
      From the mutation profiles, we were able to identify subtype outliers, ie cases
      diagnosed morphologically as one subtype but with a mutation profile suggestive
      of a different subtype. Careful review of these diagnostically challenging cases
      suggested that the original morphological classification was incorrect in most
      instances. The molecular profile of carcinosarcomas suggests two distinct
      mutation profiles for these tumours: endometrioid-type (PTEN, PIK3CA, ARID1A,
      KRAS mutations) and serous-type (TP53 and PPP2R1A mutations). While this nine
      gene panel does not allow for a purely molecularly based classification of
      endometrial carcinoma, it may prove useful as an adjunct to morphological
      classification and serve as an aid in the classification of problematic cases. If
      used in practice, it may lead to improved diagnostic reproducibility and may also
      serve to stratify patients for targeted therapeutics.

PMID- 22653806
TI  - Enantioseparation of racemic mixtures based on solvent sublation.
AB  - A method of solvent sublation was developed for the enantioseparation of racemic
      ofloxacin (rac Oflx) and racemic tryptophan (rac Trp). In this method, dibenzoyl
      L-tartaric acid (L-DBTA) and di-(2-ethylhexyl) phosphoric acid (D2EHPA) and
      sodium lauryl sulfate (SDS) were used as chiral coextractants and foamer,
      respectively. Several important parameters influencing the separation
      performances, such as pH in aqueous phase, concentrations of rac mixtures, L
      DBTA, D2EHPA, and SDS, were investigated. Under the optimal operation conditions,
      the enantiomeric excess and enantioselectivity were 60.08% and 5.58 for Oflx and
      65.09% and 6.31 for Trp, respectively. The yields of D-enantiomer and L
      enantiomer were 34.23% and 8.54% for Oflx and 18.59% and 3.93% for Trp,
      respectively. The results suggest that the enantioselectivities have been
      enhanced compared with the traditional chiral extraction. This technique is an
      efficient chiral separation method, with many advantages such as low expenditures
      of organic solvent, low consumption of chiral extractant, and easy realization of
      multistage operation.

PMID- 22653807
TI  - Volumetric MRI differences in treatment naive and chronically treated adolescents
      with ADHD-combined type.
AB  - OBJECTIVE: The purpose of this study was to determine whether there are
      differences in the volume of specific brain regions using magnetic resonance
      imaging (MRI) between children and adolescents with ADHD and controls and whether
      such differences are related to the participants' history of stimulant treatment.
      METHOD: A total of 16 healthy controls, 16 children, and adolescents with ADHD
      combined (ADHD-C) type with a history of stimulant treatment, and 13 children and
      adolescents with ADHD-C type treatment naive participated. RESULTS: Total
      frontal, prefrontal, and caudate volumes were larger for children and adolescents
      with ADHD compared with controls with no differences based on medication history
      with larger right gray and white matter prefrontal volumes in the ADHD groups. A
      medication difference was found with the right anterior cingulate cortex smaller
      in children and adolescents without a treatment history. CONCLUSION: These
      findings suggest that aberrant prefrontal and caudate volumes in ADHD-C may
      compromise functioning of the frontostriatal circuitry.

PMID- 22653808
TI  - ADHD predominantly inattentive subtype with high sluggish cognitive tempo: a new
      clinical entity?
AB  - OBJECTIVE: The authors investigate differences in the neuropsychological and
      behavioral profiles of two groups of children with ADHD, one with predominantly
      inattentive subtype of ADHD (PI) and high sluggish cognitive tempo (SCT; n = 19)
      and another formed by the rest of the sample (children with ADHD combined subtype
      and children with PI and low SCT scores; n = 68). METHOD: Instruments included
      Wechsler Intelligence Scale for Children and subtests from Developmental
      Neuropsychological Assessment, Conners' Continuous Performance Test, Behavior
      Rating Inventory of Executive Function, and Achenbach's Child Behavior Checklist
      for ages 6 to 18. RESULTS: PI with high SCT had fewer problems with sustained
      attention, and more internalizing problems, anxiety/depression, and
      withdrawn/depressed behavior, and more executive problems with self-monitoring
      than the rest of the ADHD sample. CONCLUSION: This study supports revising
      subtype's criteria and further studying the hypothesis that ADHD with high SCT
      constitutes a separate clinical entity.

PMID- 22653809
TI  - Alcohol and substance use history among ADHD adults: the relationship with
      persistent and remitting symptoms, personality, employment, and history of
      service use.
AB  - OBJECTIVE: To profile substance use, personality, service use, and employment in
      adults with ADHD. METHOD: The sample consisted of 216 consecutive referrals to an
      adult ADHD service and classified with ADHD, partially or fully remitted ADHD, or
      no ADHD. Normal controls (n = 33) were recruited from a general practitioner's
      center. Participants completed measures of alcohol and illicit substance use,
      employment, service use, ADHD symptoms, and personality. RESULTS: High rates of
      substance use were found in participants with current ADHD diagnoses. ADHD
      participants showed increased rates of personality trait or disorder scores and
      unemployment. There was some indication that those with ADHD and substance
      related impairment place higher demand on services. Individuals with partially
      remitted ADHD showed similar substance use to those with current ADHD, whereas
      those in full remission were comparable with normal controls. CONCLUSION:
      Although ADHD symptoms may remit with time, individuals retaining persisting or
      partial symptoms have substantial needs in adulthood.

PMID- 22653810
TI  - ADHD symptoms are differentially related to specific aspects of quality of life.
AB  - OBJECTIVE: The objectives of this study were to investigate the relationships
      between ADHD symptoms and specific domains of the Medical Outcomes Study 36-Item
      Short Form Health Survey (SF-36) mental component. METHOD: A sample of 149 adults
      participated in the study. Data were collected from the participant's medical
      records and from self-report questionnaires. Multiple regression analyses were
      applied to identify predictors of the SF-36 mental component outcomes. RESULTS:
      The sample was highly impaired in terms of low health-related quality of life on
      all SF-36 mental component scales. The ADHD Self-Report Scale (ASRS)
      inattentiveness was the strongest predictor of vitality and the only significant
      predictor of role-emotional outcome. The ASRS hyperactivity/impulsivity was the
      strongest predictor of social function and the only predictor of mental health
      outcome. CONCLUSION: Inattentiveness and hyperactivity/impulsivity were
      differentially related to specific quality-of-life domains. Inattentiveness was
      significantly predicting vitality and role-emotional outcomes, and
      hyperactivity/impulsivity predicted social function and mental health outcomes.

PMID- 22653811
TI  - JD induced pluripotent stem cell-derived hepatocytes faithfully recapitulate the
      pathophysiology of familial hypercholesterolemia.
AB  - Elevated levels of low-density lipoprotein cholesterol (LDL-C) in plasma are a
      major contributor to cardiovascular disease, which is the leading cause of death
      worldwide. Genome-wide association studies (GWAS) have identified 95 loci that
      associate with control of lipid/cholesterol metabolism. Although GWAS results are
      highly provocative, direct analyses of the contribution of specific allelic
      variations in regulating LDL-C has been challenging due to the difficulty in
      accessing appropriate cells from affected patients. The primary cell type
      responsible for controlling cholesterol and lipid flux is the hepatocyte.
      Recently, we have shown that cells with hepatocyte characteristics can be
      generated from human induced pluripotent stem cells (iPSCs). This finding raises
      the possibility of using patient-specific iPSC-derived hepatocytes to study the
      functional contribution of GWAS loci in regulating lipid metabolism. To test the
      validity of this approach, we produced iPSCs from JD a patient with mutations in
      the low-density lipoprotein receptor (LDLR) gene that result in familial
      hypercholesterolemia (FH). We demonstrate that (1) hepatocytes can be efficiently
      generated from FH iPSCs; (2) in contrast to control cells, FH iPSC-derived
      hepatocytes are deficient in LDL-C uptake; (3) control but not FH iPSC-derived
      hepatocytes increase LDL uptake in response to lovastatin; and (4) FH iPSC
      derived hepatocytes display a marked elevation in secretion of lipidated
      apolipoprotein B-100. CONCLUSION: Cumulatively, these findings demonstrate that
      FH iPSC-derived hepatocytes recapitulate the complex pathophysiology of FH in
      culture. These results also establish that patient-specific iPSC-derived
      hepatocytes could be used to definitively determine the functional contribution
      of allelic variation in regulating lipid and cholesterol metabolism and could
      potentially provide a platform for the identification of novel treatments of
      cardiovascular disease. (HEPATOLOGY 2012).

PMID- 22653812
TI  - Copper-mediated and copper-catalyzed cross-coupling of indoles and 1,3-azoles:
      double C-H activation.
AB  - A new bronze age: the described copper-mediated cross-coupling with double C-H
      activation can provide a convergent access to indole-containing biheteroaryls
      that are of high interest in pharmaceutical and medicinal chemistry. In this
      strategy an easily attachable and detachable 2-pyrimidyl directing group is used.
      Moreover, a variant that is catalytic in copper is achieved by using atmospheric
      oxygen as an ideal co-oxidant.

PMID- 22653813
TI  - Conflict of interest policies and disclosure requirements among European Society
      of Cardiology National Cardiovascular Journals.
AB  - Disclosure of potential conflicts of interest (COI) is used by biomedical
      journals to guarantee credibility and transparency of the scientific process. COI
      disclosure, however, is not systematically nor consistently dealt with by
      journals. Recent joint editorial efforts paved the way towards the implementation
      of uniform vehicles for COI disclosure. This paper provides a comprehensive
      editorial perspective on classical COI-related issues. New insights into current
      COI policies and practices among European Society of Cardiology national
      cardiovascular journals, as derived from a cross-sectional survey using a
      standardised questionnaire, are discussed.

PMID- 22653814
TI  - Percutaneous treatment of native aortic coarctation in adults.

PMID- 22653815
TI  - Three-dimensional computed tomography overlay for pulmonary vein antrum
      isolation: Follow-up and clinical outcomes.
AB  - BACKGROUND: To facilitate the creation of circumferential lines in pulmonary vein
      (PV) antrum isolation, three-dimensional (3D) navigation systems are used widely.
      Alternatively, 3D reconstructions of the left atrium (LA) can be superimposed
      directly on fluoroscopy to guide ablation catheters and to mark ablation sites.
      METHODS: In 71 atrial fibrillation patients circumferential PV ablation was
      performed. 3D reconstructions of the LA were derived from contrast cardiac
      computed tomography and circumferential PV isolation was performed. In subsequent
      ablation procedures, veins were re-isolated, and defragmentation or linear
      lesions were performed if necessary. RESULTS: Adequate 3D reconstructions were
      formed and registered to fluoroscopy in all patients. All veins, except 2 in one
      single patient, could be isolated, resulting in freedom of AF in 45 patients (63
      %). In 19 patients a second procedure was performed, in which 2.7 +/- 1.1 PV per
      patient were re-isolated; in 3 patients a third procedure was performed. After
      follow-up of 15 +/- 8 months, 51 (91 %) of patients with paroxysmal and 10 (67 %)
      with persistent AF were free of AF. CONCLUSIONS: The results of 3D overlay for
      circumferential PV isolation are good, although the reconduction rate and need
      for subsequent ablations remains high, and the outcomes of this technique appear
      to be equivalent to other mapping techniques.

PMID- 22653816
TI  - Loosely-guided, self-directed learning versus strictly-guided, station-based
      learning in gross anatomy laboratory sessions.
AB  - Anatomy students studying dissected anatomical specimens were subjected to either
      a loosely-guided, self-directed learning environment or a strictly-guided,
      preformatted gross anatomy laboratory session. The current study's guiding
      questions were: (1) do strictly-guided gross anatomy laboratory sessions lead to
      higher learning gains than loosely-guided experiences? and (2) are there
      differences in the recall of anatomical knowledge between students who undergo
      the two types of laboratory sessions after weeks and months? The design was a
      randomized controlled trial. The participants were 360 second-year medical
      students attending a gross anatomy laboratory course on the anatomy of the hand.
      Half of the students, the experimental group, were subjected without prior
      warning to station-based laboratory sessions; the other half, the control group,
      to loosely-guided laboratory sessions, which was the course's prevailing
      educational method at the time. The recall of anatomical knowledge was measured
      by written reproduction of 12 anatomical names at four points in time:
      immediately after the laboratory experience, then one week, five weeks, and eight
      months later. The strictly-guided group scored higher than the loosely-guided
      group at all time-points. Repeated ANOVA showed no interaction between the
      results of the two types of laboratory sessions (P = 0.121) and a significant
      between-subject effect (P <= 0.001). Therefore, levels of anatomical knowledge
      retrieved were significantly higher for the strictly-guided group than for the
      loosely-guided group at all times. It was concluded that gross anatomy laboratory
      sessions with strict instructions resulted in the recall of a larger amount of
      anatomical knowledge, even after eight months.

PMID- 22653817
TI  - Evaluation of fluoroquinolone reduced dosage regimens in elderly patients by
      using pharmacokinetic modelling and Monte Carlo simulations.
AB  - OBJECTIVES: Fluoroquinolones are widely used in geriatric patients, but elderly
      patients are known to be at increased risk of decline in renal function. As
      fluoroquinolones usually exhibit a dominant renal elimination pathway, reduced
      dosage regimens are often used in geriatric patients. Our objective was to assess
      the capability to reach a pharmacokinetic-pharmacodynamic target of efficacy with
      such reduced dosage regimens of ofloxacin, levofloxacin and ciprofloxacin in
      elderly patients. METHODS: Using Monte Carlo simulations, 1000 simulated elderly
      patients were created, based on published pharmacokinetic and pharmacodynamic
      data, and measured demographic data. Three usually proposed drug regimens taking
      renal function into account were evaluated using compartmental models. The
      probability of reaching an fAUC/MIC >100 was calculated for each regimen.
      RESULTS: For MICs <1 mg/L, all simulated patients reach the efficacy target.
      However, with higher values of MIC, the proposed regimens were inefficient for
      patients with moderate or severe renal impairment: 3.4% and 30.2% of patients
      with moderate renal impairment reached the efficacy target for ciprofloxacin and
      ofloxacin, respectively, for an MIC of 2 mg/L. For ciprofloxacin, more than 80%
      of patients with severe renal impairment were unable to reach the target fAUC/MIC
      with an MIC as low as 1 mg/L, whereas for levofloxacin, all simulated patients
      reached the efficacy target until an MIC of 4 mg/L. CONCLUSIONS: This suggests
      that the proposed dosage reduction does not allow the same exposure to be
      achieved in elderly patients with renal impairment, eventually leading to
      treatment failure or development of resistant strains.

PMID- 22653819
TI  - Invasive fungal breakthrough infections, fungal colonization and emergence of
      resistant strains in high-risk patients receiving antifungal prophylaxis with
      posaconazole: real-life data from a single-centre institutional retrospective
      observational study.
AB  - OBJECTIVES: The broad-spectrum triazole posaconazole showed promising results in
      preventing invasive fungal infections (IFIs) in high-risk patients. Concerns rise
      over the relevance of breakthrough IFIs (bIFIs) and the emergence of azole
      resistant strains. The current retrospective analysis was undertaken to evaluate
      the incidence of bIFIs and to study fungal colonization and resistance following
      posaconazole exposure. METHODS: Ninety-five patients who underwent 202 courses of
      primary antifungal prophylaxis with 200 mg of posaconazole three times daily
      during neutropenia after chemotherapy/haematopoietic stem cell transplantation
      between September 2008 and September 2010 were evaluated. An IFI was considered
      to be a bIFI if its occurrence was detected >=4 days after initiation of
      preventative posaconazole prophylaxis. RESULTS: The incidence of bIFIs was 13%
      (27/202), with 11/27 (41%) proven and 16/27 (59%) probable bIFIs. Proven
      infections were mainly localized in the lungs (85%). Species diagnosis
      exclusively revealed non-Aspergillus species, i.e. mucormycetes in 55% and yeasts
      in 45%. The median overall survival for patients with bIFIs was 5.2 months.
      Sixteen of 27 patients with bIFIs (proven and probable) succumbed. Regarding only
      proven cases, 8/11 patients died, whereas only 1/16 deaths was caused by fungal
      disease. Prospective screening confirmed colonization with yeasts in 42/202 (21%)
      courses; moulds were not identified. The spectrum of colonizing yeasts changed
      slightly over time, shifting to more rare yeasts. There were no deaths due to
      invasive yeast infections. CONCLUSIONS: A significant proportion of bIFIs,
      compared with historical data, with a shift to non-Aspergillus spp. and in
      particular to mucormycetes was observed in patients at high risk for IFI during
      posaconazole prophylaxis.

PMID- 22653821
TI  - Editorial: "crossing boundaries: stem cells, materials, and mesoscopic sciences".
AB  - "Crossing Boundaries: Stem Cells, Materials, and Mesoscopic Sciences". This
      Special Issue, edited by Prof. Anthony Ho and Prof. Norio Nakatsuji, comprises
      review articles on the interdisciplinary study of stem cells and material science
      and is a celebration of the friendship and collaboration between Heidelberg
      University and Kyoto University in Germany and Japan, respectively.

PMID- 22653824
TI  - Heidelberg-Kyoto partnership bridges life and materials sciences, strengthens
      bilateral ties.
AB  - Coinciding with the 150(th)  anniversary of German-Japanese friendship, Kyoto
      University and Heidelberg University, two universities replete with history and
      tradition strengthened their close ties at a joint meeting in Heidelberg,
      Germany, forming the core of a broad collaborative effort between the two
      countries. This forum article provides a background and overview of the
      collaborations.

PMID- 22653825
TI  - Biomaterials in medical devices: an interview with Jorg Vienken of Fresenius
      Medical Care, Germany.
AB  - Biomaterial and biopolymer research have significant impact on the development as
      well as application of biotechnology. Biotechnology Journal recently attended the
      "Nanomaterials for Biomedical Technologies 2012" conference. We were privileged
      to have the opportunity to ask Prof. Dr. Jorg Vienken, VP of BioSciences at
      Fresenius Medical Care, a few questions relating to medical devices, the
      importance of publishing for industry, and also his advice for young
      scientists/engineers looking for a career in industry.

PMID- 22653826
TI  - Systematic approaches to dissect biological processes in stem cells by image
      based screening.
AB  - High-throughput RNAi or small molecule screens have proven to be powerful
      methodologies for the systematic dissection of cellular processes. In model
      organisms and cell lines, large-scale screens have identified key components of
      many cellular pathways and helped to identify novel targets in disease-relevant
      pathways. Image-based high-content screening has become an increasingly important
      tool in high-throughput screening, enabling changes in phenotype characteristics,
      such as cell morphology and cell differentiation, to be monitored. In this
      review, we discuss the use of image-based screening approaches to explore the
      behavior of adult, embryonic, and induced pluripotent stem cells. First, we
      review how current pluripotency and differentiation assays can be adapted to high
      throughput formats. We then describe general aspects of image-based screening of
      cells and present an outlook on challenges for screening stem cells.

PMID- 22653830
TI  - A comparison of outcome from surgical and endovascular salvage procedures for
      occluded arteriovenous fistulae.

PMID- 22653829
TI  - Impaired decidual natural killer cell regulation of vascular remodelling in early
      human pregnancies with high uterine artery resistance.
AB  - During human pregnancy, natural killer (NK) cells accumulate in the maternal
      decidua, but their specific roles remain to be determined. Decidual NK (dNK)
      cells are present during trophoblast invasion and uterine spiral artery
      remodelling. These events are crucial for successful placentation and the
      provision of an adequate blood supply to the developing fetus. Remodelling of
      spiral arteries is impaired in the dangerous pregnancy complication pre
      eclampsia. We studied dNK cells isolated from pregnancies at 9-14 weeks'
      gestation, screened by uterine artery Doppler ultrasound to determine resistance
      indices which relate to the extent of spiral artery remodelling. dNK cells were
      able to promote the invasive behaviour of fetal trophoblast cells, partly through
      HGF. Cells isolated from pregnancies with higher resistance indices were less
      able to do this and secreted fewer pro-invasive factors. dNK cells from
      pregnancies with normal resistance indices could induce apoptotic changes in
      vascular smooth muscle and endothelial cells in vitro, events of importance in
      vessel remodelling, partly through Fas signalling. dNK cells isolated from high
      resistance index pregnancies failed to induce vascular apoptosis and secreted
      fewer pro-apoptotic factors. We have modelled the cellular interactions at the
      maternal-fetal interface and provide the first demonstration of a functional role
      for dNK cells in influencing vascular cells. A potential mechanism contributing
      to impaired vessel remodelling in pregnancies with a higher uterine artery
      resistance is presented. These findings may be informative in determining the
      cellular interactions contributing to the pathology of pregnancy disorders where
      remodelling is impaired, such as pre-eclampsia.

PMID- 22653831
TI  - Superficialization of the radial artery--an alternative secondary vascular
      access.
AB  - PURPOSE: The standard approach in patients with a clotted arteriovenous fistula
      (AVF) on the forearm is the creation of another vascular access on the arm using
      the patient's own vessels or a prosthetic graft. Here we propose another option
      as secondary angioaccess for chronic hemodialysis (HD): superficialization of the
      radial artery. METHODS: Indications for the procedure were 1) long-standing
      forearm AVF that has irreversibly clotted and/or central vein stenosis resistant
      to angioplasty; 2) patients who have no other prospect for forearm or even
      brachial AVF. The procedure was undertaken in 7 chronic HD patients dialyzed by
      forearm AVF for 27+/-26 months. RESULTS: In one case the superficialization was
      abandoned intra-operatively due to small diameter of the artery (<4 mm). Five of
      6 elevated arteries were patent and the follow-up period ranges from 11 to 15
      (median 12) months. In 1 male patient with prothrombin G20210A mutation the
      artery clotted after 13 months of usage. CONCLUSIONS: Superficialized radial
      artery was successfully used for hemodialysis over one year. The only
      prerequisite for safe repeated puncture is a patent and enlarged radial artery.
      Due to avoidance of arteriovenous shunt this access type may be particularly
      suitable for patients with cardiac failure.

PMID- 22653832
TI  - Surgical treatment modalities for complicated aneurysms and pseudoaneurysms of
      arteriovenous fistulas.
AB  - PURPOSE: This study was designed to determine the clinical presentation,
      characteristics, and management of aneurysm/pseudoaneurysm formation (APF) in
      dialysis access fistulas. METHODS: The treatment methods and outcomes of 31
      patients who underwent surgery for APF in dialysis access fistulas were
      retrospectively reviewed over a 9-year period. RESULTS: We performed 1558
      operations for arteriovenous fistulas (AVFs) between 2000 and 2009 at our centre.
      Of the 1558 operations, 35 were carried out for APFs (2.2%) on 31 patients.
      Thirty of these operations were restorative. Twenty-two (71%) of these patients
      had their original access done elsewhere, and all corrective surgeries were
      performed at our hospital. Approximately 52% of the subjects were female, with a
      mean age of 45.7 +/- 17 years. The mean duration of end-stage renal disease was
      70.2 +/- 51.5 months. The mean number of AVFs per patient was 2.2 +/- 1.5.
      Synthetic grafts were used in five patients (16.1%). Most of the procedures were
      left-sided (67.7%) and brachial-cephalic fistulas (48.3%). Among 31
      complications, 22 were arterial/venous aneurysms (71%) and nine were
      pseudoaneurysms (29%). Fourteen patients (46.6%) were treated by excision of the
      aneurysm and primary suture repair. The post-intervention primary patencies for
      all revised APFs were 68%, 56%, and 52% at 1, 6, and 12 months, respectively.
      Dysfunction of AVF (16.1%) and bleeding (12.9%) were the most encountered
      complications after aneurysmectomy. CONCLUSION: Reformative operations should be
      considered in cases of urgency and irresponsiveness to endovascular surgery
      rather than closing the fistulas directly, as it prolongs the duration of AVF
      patency.

PMID- 22653833
TI  - Central venous catheter-induced cardiac tamponade: a preventable complication.

PMID- 22653834
TI  - Strengths-based cognitive-behavioural therapy: a four-step model to build
      resilience.
AB  - Padesky and Mooney's four-step Strengths-Based cognitive-behavioural therapy
      (CBT) model is designed to help clients build positive qualities. This article
      shows how it can be used to build and strengthen personal resilience. A
      structured search for client strengths is central to the approach, and methods
      designed to bring hidden strengths into client awareness are demonstrated through
      therapist-client dialogues. Development of positive qualities requires a shift in
      therapy perspective and different therapy methods from those employed when
      therapy is designed to ameliorate distress. Required adjustments to classic CBT
      are highlighted with specific recommendations for clinical modifications designed
      to support client development of resilience such as a focus on current strengths,
      the constructive use of imagery and client-generated metaphors. Although the
      focus of this article is on resilience, this Strengths-Based CBT model offers a
      template that also can be used to develop other positive human qualities.

PMID- 22653835
TI  - Phase behavior and mesophase structures of 1,3,5-benzene- and 1,3,5
      cyclohexanetricarboxamides: towards an understanding of the losing order at the
      transition into the isotropic phase.
AB  - One of the simplest and most-versatile motifs in supramolecular chemistry is
      based on 1,3,5-benzenetricarboxamides. Variation of the core structure and subtle
      changes in the structures of the lateral substituents govern the self-assembly
      and determine the phase behavior. Herein, we provide a comprehensive comparison
      between the phase behavior and mesophase structure of a series of 1,3,5-benzene-
      and 1,3,5-cyclohexanetricarboxamides that contain linear and branched alkyl
      substituents. Depending on the substituent, different crystalline, plastic
      crystalline, and liquid crystalline phases were formed. The relatively rare
      columnar nematic (N(C)) phase was only observed in cyclohexane-based trisamides
      that contained linear alkyl substituents. Of fundamental interest in liquid
      crystalline supramolecular systems is the transition from the mesomorphic state
      into the isotropic state and, in particular, the question of how the order
      decreases. Temperature-dependent IR spectroscopy and XRD measurements revealed
      that columnar H-bonded aggregates were still present in the isotropic phase. At
      the clearing transition, mainly the lateral order was lost, whilst shorter
      columnar aggregates still remained. A thorough understanding of the phase
      behavior and the mesophase structure is relevant for selecting processing
      conditions that use supramolecular structures in devices or as fibrillar
      nanomaterials.

PMID- 22653836
TI  - Multiple-charged P1-centered cations: perspectives in synthesis.

PMID- 22653838
TI  - Use of intubation introducers through a supraglottic airway to facilitate
      tracheal intubation: a brief review.
AB  - PURPOSE: This article is a narrative review regarding the usage and effectiveness
      of introducers or catheters to facilitate tracheal intubation through a
      supraglottic airway (SGA) as an alternative intubation technique in normal and
      difficult airway management. SOURCES: Relevant articles were obtained through
      Medline (1948-July 2011). The articles were subsequently cross-referenced for
      additional literature, and only articles published in English were included.
      PRINCIPAL FINDINGS: In this review, we consider 32 reports using the LMA
      ClassicTM, LMA UniqueTM, LMA ProSealTM, LMA SupremeTM, AuraOnceTM, and i-gelTM as
      SGA conduits for intubation. In 13 articles, the use of an Aintree Intubation
      Catheter was described as an intubation introducer and resulted in high success
      rates in both elective and emergent situations. Eight studies used a guidewire
      exchange catheter technique. Although blind intubation using a guidewire resulted
      in a high failure rate, these studies found that using a bronchoscope improved
      successful intubation. Ten studies showed that insertion of a gum elastic bougie
      with a bronchoscope as an intubation introducer has high success rates compared
      with blind bougie insertion. One article described the use of a small
      endotracheal tube as an intermediary for tracheal intubation. CONCLUSIONS: In
      failed intubation scenarios, supraglottic airways, such as the LMA ClassicTM or
      LMA ProSealTM can serve as a conduit for tracheal intubation. A number of
      techniques using introducers or catheters can facilitate the insertion of an
      adequately sized endotracheal tube, particularly guided by a bronchoscope. Usage
      of introducers or catheters through a supraglottic airway may be a useful
      alternative intubation technique in difficult airway management.

PMID- 22653839
TI  - Allergic contact dermatitis at the epidural catheter site due to Mastisol(r)
      liquid skin adhesive.

PMID- 22653837
TI  - Cyclic AMP/PKA-dependent paradoxical activation of Raf/MEK/ERK signaling in
      polycystin-2 defective mice treated with sorafenib.
AB  - Mutations in polycystins are a cause of polycystic liver disease. In polycystin-2
      (PC2)-defective mice, cyclic adenosine monophosphate (cAMP)/protein kinase A
      (PKA)-dependent activation of the Rat Sarcoma (Ras)/rapidly accelerated
      fibrosarcoma (Raf)/mitogen signal-regulated kinase-extracellular signal-regulated
      kinase (ERK) 1/2 pathway stimulates the growth of liver cysts. To test the
      hypothesis that sorafenib, a Raf inhibitor used for the treatment of liver and
      kidney cancers, inhibits liver cyst growth in PC2-defective mice, we treated PC2
      (i.e., Pkd2(flox/-) :pCxCreER(TM) [Pkd2cKO]) mice with sorafenib-tosylate for 8
      weeks (20-60 mg/kg/day). Sorafenib caused an unexpected increase in liver cyst
      area, cell proliferation (Ki67), and expression of phosphorylated ERK (pERK)
      compared with Pkd2cKO mice treated with vehicle. When given to epithelial cells
      isolated from liver cysts of Pkd2cKO mice (Pkd2cKO-cells), sorafenib
      progressively stimulated pERK1/2 and cell proliferation [3-(4,5-dimethylthiazol-2
      yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and
      bromodeoxyuridine assay (MTS)] at doses between 0.001 and 1 MUM; however, both
      pERK1/2 and cell proliferation significantly decreased at the dose of 10 MUM. Raf
      kinase activity assay showed that whereas B-Raf is inhibited by sorafenib in both
      wild-type (WT) and Pkd2cKO cells, Raf-1 is inhibited in WT cells but is
      significantly stimulated in Pkd2cKO cells. In Pkd2cKO cells pretreated with the
      PKA inhibitor 14-22 amide, myristolated (1 MUM) and in mice treated with
      octreotide in combination with sorafenib, the paradoxical activation of
      Raf/ERK1/2 was abolished, and cyst growth was inhibited. CONCLUSION: In PC2
      defective cells, sorafenib inhibits B-Raf but paradoxically activates Raf-1,
      resulting in increased ERK1/2 phosphorylation, cell proliferation, and cyst
      growth in vivo. These effects are consistent with the ability of Raf inhibitors
      to transactivate Raf-1 when a PKA-activated Ras promotes Raf-1/B-Raf
      heterodimerization, and are inhibited by interfering with cAMP/PKA signaling both
      in vitro and in vivo, as shown by the reduction of liver cysts in mice treated
      with combined octreotide and sorafenib.

PMID- 22653840
TI  - Brief review: theory and practice of minimal fresh gas flow anesthesia.
AB  - PURPOSE: The aim of this brief review is to provide an update on the theory
      regarding minimal fresh gas flow techniques for inhaled general anesthesia. The
      article also includes an update and discussion of the practical aspects
      associated with minimal-flow anesthesia, including the advantages, potential
      limitations, and safety considerations of this important anesthetic technique.
      PRINCIPAL FINDINGS: Reducing the fresh gas flow to < 1 L.min(-1) during
      maintenance of anesthesia is associated with several benefits. Enhanced
      preservation of temperature and humidity, cost savings through more efficient
      utilization of inhaled anesthetics, and environmental considerations are three
      key reasons to implement minimal-flow and closed-circuit anesthesia, although
      potential risks are hypoxic gas mixtures and inadequate depth of anesthesia. The
      basic elements of the related pharmacology need to be considered, especially
      pharmacokinetics of the inhaled anesthetics. The third-generation inhaled
      anesthetics, sevoflurane and desflurane, have low blood and low tissue
      solubility, which facilitates rapid equilibration between the alveolar and effect
      site (brain) concentrations and makes them ideally suited for low-flow
      techniques. The use of modern anesthetic machines designed for minimal-flow
      techniques, leak-free circle systems, highly efficient CO(2) absorbers, and the
      common practice of utilizing on-line real-time multi-gas monitor, including
      essential alarm systems, allow for safe and cost-effective minimal-flow
      techniques during maintenance of anesthesia. The introduction of new anesthetic
      machines with built-in closed-loop algorithms for the automatic control of
      inspired oxygen and end-tidal anesthetic concentration will further enhance the
      feasibility of minimal-flow techniques. CONCLUSIONS: With our modern anesthesia
      machines, reducing the fresh gas flow of oxygen to 0.3-0.5 L.min(-1) and using
      third-generation inhaled anesthetics provide a reassuringly safe anesthetic
      technique. This environmentally friendly practice can easily be implemented for
      elective anesthesia; furthermore, it will facilitate cost savings and improve
      temperature homeostasis.

PMID- 22653841
TI  - [A case of rocuronium-induced anaphylactic shock, improved by sugammadex].

PMID- 22653842
TI  - Cysteine cathepsin S processes leptin, inactivating its biological activity.
AB  - Leptin is a 16  kDa hormone mainly produced by adipocytes that plays an important
      role in many biological events including the regulation of appetite and energy
      balance, atherosclerosis, osteogenesis, angiogenesis, the immune response, and
      inflammation. The search for proteolytic enzymes capable of processing leptin
      prompted us to investigate the action of cysteine cathepsins on human leptin
      degradation. In this study, we observed high cysteine peptidase expression and
      hydrolytic activity in white adipose tissue (WAT), which was capable of degrading
      leptin. Considering these results, we investigated whether recombinant human
      cysteine cathepsins B, K, L, and S were able to degrade human leptin. Mass
      spectrometry analysis revealed that among the tested enzymes, cathepsin S
      exhibited the highest catalytic activity on leptin. Furthermore, using a Matrigel
      assay, we observed that the leptin fragments generated by cathepsin S digestion
      did not exhibit angiogenic action on endothelial cells and were unable to inhibit
      food intake in Wistar rats after intracerebroventricular administration. Taken
      together, these results suggest that cysteine cathepsins may be putative leptin
      activity regulators in WAT.

PMID- 22653843
TI  - Relevance of increased serum cystatin C to vascular alterations in obese
      children.
AB  - OBJECTIVE: Epidemiological studies report a positive relationship between serum
      cystatin C and cardiovascular outcomes in adults. Here, we tested the relevance
      of cystatin C as a biomarker for early vascular alterations in severely obese
      children. METHODS: Two hundred nineteen obese (140 girls; age = 11.7 +/- 2.7
      years, BMI Z-score = 4.7 +/- 1.2 SD) and 262 non-obese children (129 girls; age =
      11.6 +/- 0.6 years, body mass index [BMI] Z-score = 0.1 +/- 1.0 SD). Serum
      cystatin C was measured by immunonephelometry. Intima media thickness (IMT),
      incremental elastic modulus, and flow-mediated and glyceryl-trinitrate-mediated
      dilations were determined at the common carotid artery and the brachial artery in
      obese children. RESULTS: Obese children had significantly higher serum cystatin C
      than normal weight controls (0.86 +/- 0.01 vs. 0.80 +/- 0.01, P < 0.0001). In
      obese children, serum cystatin C correlates positively with BMI and the
      homeostasis model assessment index and negatively with the quantitative insulin
      sensitivity check index and adiponectin. A positive relationship was found
      between serum cystatin C and carotid IMT (r = 0.23, P = 0.0005), which remained
      significant in multivariate models adjusted for BMI (P = 0.01) and adiponectin
      with a trend towards significance (P = 0.05). CONCLUSION: This study positions
      cystatin C and adiponectin as covariables associated with arterial wall thickness
      in obese children. Although the underlying pathophysiology linking cystatin C to
      early vascular disease remains to be deciphered, cystatin C may represent a novel
      adipose tissue-derived biomarker implicated in obesity-related comorbidities
      early in life.

PMID- 22653844
TI  - Label-free homogeneous immunosensor based on FRET for the detection of virus
      antibody in serum.

PMID- 22653845
TI  - Activation of Wnt signalling promotes development of dysplasia in Barrett's
      oesophagus.
AB  - Barrett's oesophagus is a precursor of oesophageal adenocarcinoma, via intestinal
      metaplasia and dysplasia. Risk of cancer increases substantially with dysplasia,
      particularly high-grade dysplasia. Thus, there is a clinical need to identify and
      treat patients with early-stage disease (metaplasia and low-grade dysplasia) that
      are at high risk of cancer. Activated Wnt signalling is critical for normal
      intestinal development and homeostasis, but less so for oesophageal development.
      Therefore, we asked whether abnormally increased Wnt signalling contributes to
      the development of Barrett's oesophagus (intestinal metaplasia) and/or dysplasia.
      Forty patients with Barrett's metaplasia, dysplasia or adenocarcinoma underwent
      endoscopy and biopsy. Mice with tamoxifen- and beta-naphthoflavone-induced
      expression of activated beta-catenin were used to up-regulate Wnt signalling in
      mouse oesophagus. Immunohistochemistry of beta-catenin, Ki67, a panel of Wnt
      target genes, and markers of intestinal metaplasia was performed on human and
      mouse tissues. In human tissues, expression of nuclear activated beta-catenin was
      found in dysplasia, particularly high grade. Barrett's metaplasia did not show
      high levels of activated beta-catenin. Up-regulation of Ki67 and Wnt target genes
      was also mostly associated with high-grade dysplasia. Aberrant activation of Wnt
      signalling in mouse oesophagus caused marked tissue disorganization with features
      of dysplasia, but only selected molecular indicators of metaplasia. Based on
      these results in human tissues and a mouse model, we conclude that abnormal
      activation of Wnt signalling likely plays only a minor role in initiation of
      Barrett's metaplasia but a more critical role in progression to dysplasia.

PMID- 22653846
TI  - Comparison of four shape features for detecting hippocampal shape changes in
      early Alzheimer's.
AB  - We compare four methods for generating shape-based features from 3D binary images
      of the hippocampus for use in group discrimination and classification. The first
      method we investigate is based on decomposing the hippocampal binary segmentation
      onto an orthonormal basis of spherical harmonics, followed by computation of
      shape invariants by tensor contraction using the Clebsch-Gordan coefficients. The
      second method we investigate is based on the classical 3D moment invariants;
      these are a special case of the spherical harmonics-based tensor invariants. The
      third method is based on solving the Helmholtz equation on the geometry of the
      binary hippocampal segmentation, and construction of shape-descriptive features
      from the eigenvalues of the Fourier-like modes of the geometry represented by the
      Laplacian eigenfunctions. The fourth method investigates the use of initial
      momentum obtained from the large-deformation diffeomorphic metric mapping method
      as a shape feature. Each of these shape features is tested for group differences
      in the control (Clinical Dementia Rating Scale CDR 0) and the early (very mild)
      Alzheimer's (CDR 0.5) population. Classification of individual shapes is
      performed via a linear support vector machine based classifer with leave-one-out
      cross validation to test for overall performance. These experiments show that all
      of these feature computation approaches gave stable and reasonable classification
      results on the same database, and with the same classifier. The best performance
      was achieved with the shape-features constructed from large-deformation
      diffeomorphic metric mapping-based initial momentum. 

PMID- 22653847
TI  - On the P-coordinating limit of NHC-phosphenium cations toward Rh(I) centers.
AB  - Two types of imidazoliophosphane with additional electron-withdrawing
      substituents, such as alkoxy or imidazolio groups, are experimentally described
      and theoretically studied. Diethyl N,N'-2,4,6-methyl(phenyl)imidazoliophosphonite
      is shown to retain a P-coordinating ability toward a {RhCl(cod)} (cod = cycloocta
      1,5-diene) center, thus competing with the cleavage of the labile C-P bond.
      Derivatives of N,N'-phenylene-bridged diimidazolylphenylphosphane were isolated
      in good yield. Whereas the dicationic phosphane proved to be inert in the
      presence of [{RhCl(cod)}(2)], the monocationic counterpart was shown to retain
      the P-coordinating ability toward a {RhCl(cod)} center, thus competing with the N
      coordinating ability of the nonmethylated imidazolyl substituent. The ethyl
      phosphinite version of the dication, thus possessing an extremely electron-poor
      P(III) center, was also characterized. According to the difference between the
      calculated homolytic and heterolytic dissociation energies, the N(2)C???P bond of
      imidazoliophosphanes with aryl, amino, or alkoxy substituents on the P atom is
      shown to be of dative nature. The P-coordinating properties of
      imidazoliophosphanes with various combinations of phenyl or ethoxy substituents
      on the P atom and those of six diimidazolophosphane derivatives with zero, one,
      or two methylium substituents on the N atom, were analyzed by comparison of the
      corresponding HOMOs and LUMOs and by calculation of the IR C=O stretching
      frequencies of their [RhCl(CO)(2)] complexes. Comparison of the nu(CO)  values
      allows the family of the electron-poor Im(+) PRR' (Im = imidazolyl) potential
      ligands to be ranked in the following order versus (R,R'):
      P(OEt)(3)<(Ph,Ph)<(Ph,OEt)<(OEt,OEt)<PF(3)<(Ph,Im)<(Ph,Im(+))<(OEt,Im(+)). The
      (Ph,Im) representative is therefore the least electron-donating phosphane for
      which coordinating behavior toward a Rh(I) center has been experimentally
      evidenced to date. Ultimate applications in catalysis could be envisaged.

PMID- 22653848
TI  - Efficient modeling of symmetric protein aggregates from NMR data.
AB  - An efficient approach to determine the structures of symmetric protein aggregates
      from liquid and solid-state NMR data is presented. Any symmetry can be used
      (cyclic or dihedral point symmetries, helical symmetries, crystallographic
      symmetries). Because the starting point is the random structure of the monomer,
      the knowledge of the 3D structure of the monomer is not required.

PMID- 22653849
TI  - Toxicokinetic and toxicodynamic model for diazinon toxicity--mechanistic
      explanation of differences in the sensitivity of Daphnia magna and Gammarus
      pulex.
AB  - A mechanistic toxicokinetic and toxicodynamic model for acute toxic effects
      (immobilization, mortality) of the organothiophosphate insecticide diazinon in
      Daphnia magna is presented. The model was parameterized using measured external
      and internal (whole-body) concentrations of diazinon, its toxic metabolite
      diazoxon, and the inactive metabolite 2-isopropyl-6-methyl-4-pyrimidinol, plus
      acetylcholinesterase (AChE) activity measured during exposure to diazinon in
      vivo. The toxicokinetic and toxicodynamic model provides a coherent picture from
      exposure to the resulting toxic effect on an organism level through internally
      formed metabolites and the effect on a molecular scale. A very fast reaction of
      diazoxon with AChE (pseudo first-order inhibition rate constant k(i) = 3.3 h(-1))
      compared with a slow formation of diazoxon (activation rate constant k(act) =
      0.014 h(-1)) was responsible for the high sensitivity of D. magna toward
      diazinon. Recovery of AChE activity from inhibition was slow and rate-determining
      (99% recovery within 16 d), compared with a fast elimination of diazinon (99%
      elimination within 17 h). The obtained model parameters were compared with
      toxicokinetic and toxicodynamic parameters of Gammarus pulex exposed to diazinon
      from previous work. This comparison revealed that G. pulex is less sensitive
      because of a six times faster detoxification of diazinon and diazoxon and an
      approximately 400 times lower rate for damage accrual. These differences
      overcompensate the two times faster activation of diazinon to diazoxon in G.
      pulex compared to D. magna. The present study substantiates theoretical
      considerations that mechanistically based effect models are helpful to explain
      sensitivity differences among different aquatic invertebrates.

PMID- 22653850
TI  - [Mating behavior and birth seasonality of black-and-white snub-nosed monkeys
      (Rhinopithecus bieti) at Mt. Lasha].
AB  - Copulation patterns are important to understanding male mating strategies and
      stabilization strategies of social organizations in primates. However,
      information on copulation patterns of Asian primates is relatively rare. This
      study was undertaken to collect data on mating behavior and birth seasonality of
      Black-and-white Snub-nosed monkeys (Rhinopithecus bieti) using all occurrence
      sampling and Focal animal-scan sampling methods at Mt. Lasha, between January and
      December, 2011. Our study focused on observing mating frequency and birth rates.
      Snub-nosed monkeys mate year round, with two observable peaks: one reproductive
      peak during the mating season, roughly from August to October, and a second non
      breeding peak during the birth season. It is unclear what biological significance
      this non-reproductive mating peak has. During our observation, we noted a lower
      ratio of mount to ejaculation and rare ejaculatory copulations, which indicated
      that every mating would not result in ejaculation. This study corroborates the
      previous view that the Rhinopithecus bieti's copulatory pattern is likely
      multiple-mount ejaculation (MME) or at the upper part of mating continuum of
      single-mount ejaculation (SME) toward MME. More ejaculatory copulations initiated
      by males than females indicate that MME is not only a mating strategy of males,
      but that males can influence the position of their copulatory pattern on the
      continuum between SME and MME. The mating frequencies significantly correlated
      with the birth rates with a delay of 6 to 7 months. Monkeys gave birth within a
      strict seasonality with a birth peak of March, which confirms the previous view.
      Infants were born with a certain degree of synchronization, but different
      populations displayed different modes of synchronizations.

PMID- 22653851
TI  - [Two distinct parts within the song of Phoenicurus auroreus, and individual
      identification on the basis of the song].
AB  - Bird song has two key functions: attraction and competition. The structures of
      these songs have been shaped by both intra- and intersexual selection.
      Accordingly, there are some species that appear to use different parts of song to
      attract females and repel males. Alongside this functional separation, the
      structure of song can also have significant divergence. We studied the songs from
      32 individuals of Phoenicurus auroreus, recorded in Beijing Xiaolongmen forest
      Park during the 2011 breeding season. The song of Phoenicurus auroreus consists
      of two distinct parts, a stereotyped and variable part. Significant differences
      between these two parts were observed between all the variables we measured.
      Based on the stereotyped part, the rate of correct individual identification is
      satisfactory, and most of songs can be correctly classified.

PMID- 22653852
TI  - [Distribution and changes in species composition and abundance of ichthyoplankton
      in the Yangtze estuary].
AB  - Based on four surveys of eggs and larvae in the Yangtze estuary in 2005 (April
      and November) and 2006 (April and September), combined with the historical data
      of the wetland in 1990 (September) and 1991 (March), we analyzed seasonal changes
      in fish species composition and quantity of ichthyoplankton. Thirty-six species
      of egg and larvae were collected and marine fish species were the highest
      represented ecological guild. Average fish species and average abundance in
      spring were lower than in autumn for every survey. The total number of eggs in
      brackish water was higher than in fresh water, but the total number of larvae and
      juveniles in brackish water was lower. The abundance of eggs and larvae during
      from 2005 to 2006 in both spring and autumn was higher compared to those from
      1990 to 1991. Obvious differences in species composition in September between
      1990 and 2006 were found, especially for Erythroculter ilishaeformis and
      Neosalanx taihuensis. Fish species composition and quantity within the
      ichthyoplankton community has obviously changed in the Yangtze estuary over the
      last 20 years.

PMID- 22653853
TI  - [Development of the lateral line system in juvenile Siberian sturgeon (Acipenser
      baerii)].
AB  - The Siberian sturgeon (Acipenser baerii Brandt), a chondrostean, occupies an
      important position in the evolution of the electroreceptor. In order to more
      fully understanding the evolution of these receptors, we examined the development
      of the lateral line system during early ontogeny of the Siberian sturgeon by
      using light and scanning electron microscopes. We detected four major events in
      this process: the lateral line placodal development, the sensory ridge formation,
      the receptor formation and the canal formation. On day 1 of post hatching, all
      six lateral line placodes are present and the posterior lateral line placode
      starts actively migrating posteriorly along the mid-line of the trunk, depositing
      neuromasts at intervals on the way of migration. The other lateral line placodes
      elongate to form sensory ridges according to its destination line pattern over
      the head, all containing primordial neuromasts. By day 7, ampullary organs rise
      from the lateral zones of the ventral of the head, though this may lag up to one
      week behind of that of the neuromasts. On day 9, the epidermis under the
      neuromast slowly invaginates, and the bony lateral line canals begin to form.
      Towards day 29, the epidermal cells surrounded some single openings of the
      ampullary organs at the ventral surface of the head, begin to migrate, and then
      transform into 3 to 4 aggregate openings. By this point, abundant microvilli are
      visible on the surface of the receptor epithelium, similar to the structure in
      elasmobranches and other sturgeons. On the day 57 of post hatching, the trunk
      canal is fully embedded into the lateral scutes. By then, the majority of
      ampullary organs are highly concentrated on the ventral rostrum, arranged in
      clusters of 3-4, distributing closely such as the shape of quincunx, thus
      completing the formation of the lateral line system.

PMID- 22653854
TI  - [Allometry of scales in Chinese pangolins (Manis pentadactyla) and Malayan
      pangolins (Manis javanica) and application in judicial expertise].
AB  - Pangolins are unique mammals in that they possess scales that serve a protective
      biological function. As an important raw material of traditional medicine,
      illegal trades of these scales are frequent and difficult to investigate or
      prosecute. We used allometric models of dry weight of scales to compare 35
      Chinese pangolins (Manis pentadactyla) and 119 Malayan pangolins (Manis
      javanica). Our results showed that the dry weight of scales increases
      significantly faster with the length of head and body in Malayan pangolins
      (P=0.005), while dry weight of scales is positive (slope=3.725) in Malayan
      pangolins but isometric (slope=3.105) in Chinese pangolins. The differences in
      morphology between these species may reflect an evolutionary adaptation to
      different environments; Malayan pangolins in tropical regions appear to suffer
      from greater predation pressure than Chinese pangolins in temperate regions. We
      advise the conversion standards between dry weight of scales and number of
      individuals as 573.47 g in Chinese pangolins and 360.51 g in Malayan pangolins
      respectively, and when two are mixed together, average above two parameters of
      the median at 466.99 g. We propose these measurements be used as judicial
      evidences in forensic identification of related cases.

PMID- 22653855
TI  - [Measuring the estrus cycle and its effect on superovulation in mice].
AB  - This study compares superovulation efficiency during different stages of the
      estrus cycle in mice by investigating the pudendum appearance, vaginal epithelial
      cell type, and the follicular development dynamics, in relation to the estrus
      cycle. We determined the stages of the estrus cycle by observing the pudendum and
      making vaginal smears of the Kunming mouse, and ascertaining the follicular
      development by making paraffin sections. Based on the observation, mice in stages
      of proestrus, oestrus, metoestrus and dioestrus were superovulated respectively,
      and their follicular developments and embryo collection results were tracked to
      ascertain the appropriate estrus cycle stage for superovulation. Our data showed
      that pudendum appearance and vaginal smears could effectively distinguish
      different stages of the estrus cycle and that ovarian tissue observation showed
      that follicular development, corpus luteum formation and luteolysis were regular
      during the estrus cycle. Likewise, during the estrus cycle of the Kunming mouse,
      pudendum appearance, vaginal epithelial cell type and follicular development were
      relational to one another. Superovulating mice in different stages of the estrus
      cycle showed marked differences both in pregnancy rate and average number of
      embryos collected. Proestrus was significantly better than metoestrus and
      dioestrus (P<0.05), and better than oestrus, but the difference between them was
      not significant (P>0.05).  We suggest that pudendum appearance and vaginal smears
      can be used to distinguish estrus cycle stages and that proestrus is the optimal
      stage of the estrus cycle for superovulation.

PMID- 22653856
TI  - [Cryopreservation of sperm from Neolissochilus benasi].
AB  - Cryopreservation of sperm from Neolissochilus benasi was studied in 2011. The
      effects of various cryoprotectants of different concentrations, dilution ratios
      of milt to extender, storage volume and thawing temperature on motility of post
      thawing of spermatozoa were examined to optimize cryopreservation procedures.
      Semen was stored in liquid nitrogen in 1.8 mL cryovial for 24 h, and the
      intensity of sperm motility was measured before and after cryopreservation. Post
      thawing motility of frozen sperm obtained with cryoprotectants 10% MeOH or 15% EG
      were higher than for others. The most effective dilution ratio of milt to
      extender is 1:7. The maximal storage volume is 60 MUL of 1.8 mL cryovial and the
      optimal sperm equilibration period in the extender D-15+10% MeOH was between 10
      60 min. Thawing was optimal in a 37 Degrees Celsius water bath. When fresh sperm
      motility is (62.33+/-2.05)%, this cryopreservation protocol resulted in frozen
      thawed semen with 20%-30% motile. The overall effect is not ideal, and cannot
      achieve extensive application. Different breeding management of different ground
      protection may have contributed to this result. Therefore, it is necessary to
      reduce stress capture induced in management of parent fish and provide suitable
      forming conditions. In the ex situ conservation of rare fish the broodstocks
      management of males is as important as that for females and the key to obtaining
      high quality larval fish.

PMID- 22653857
TI  - [Phenotype analysis and mutant gene location of ventral yellow mouse (VY(Slac))].
AB  - The ventri-yellow pigmentation mouse (temporarily named VY(Slac)) arose
      spontaneously in the C57BL/6J inbred mouse strain, found and bred by Shanghai
      SLAC Laboratory Animal Co., Ltd. VY(Slac) presented a special phenotype marked by
      yellow coat on the ventral surface of neck and trunk that was without melanin
      deposition but maintained a normal structure. The number of melanocytes in
      epidermis and melanin in hair follicle of the abdominal skin of the mutant mouse
      were less than that of their background strain, while there was no significant
      difference between the dorsal skins of the two strains. This mutant phenotype was
      inherited as single-gene dominant inheritance, confirmed by genetic experiment,
      and there was no significant difference between VY(Slac) and B(6) for other
      biological parameters such as weight, anatomic and histological structures of
      major organs and blood physiology. When the linkage relationship between the
      genomic DNA samples of F(2) 48 mice (VY(Slac)D(2)F(1)*D(2)) and mutant phenotype
      were evaluated, the mutant gene was confirmed on chromosome 2 near D2Mit229. New
      microsatellite and SNP markers were selected to amplify genomic DNA samples of
      196 F(2) mice and the mutant gene was narrowed down to 5.3 Mb region between
      rs13476833 and rs27310903 on chromosome 2. The preliminary results of our
      phenotype analysis and gene location provides a solid basis for further
      identification of this mutant gene.

PMID- 22653858
TI  - [Effects of compensatory growth on the levels of IGF-1, IGFBP-1 and expressions
      of IGF-1 mRNA, IGF-1R mRNA in Carassius auratus gibelio].
AB  - We studied the effects of starvation and re-feeding on the levels of plasma IGF
      1, IGFBP-1 and expressions of hepatic IGF-1 mRNA and muscle IGF-1R mRNA in
      Carassius auratus gibelio. During the two week starvation period, both the levels
      of plasma IGF-1 and IGFBP-1 decreased and were significantly lower on day 14 (P
      <0.05). On the first day of re-feeding, the level of plasma IGF-1 increased
      sharply, to the level of control group, and had no significant changes for the
      remaining days. While the level of plasma IGFBP-1 was still greatly lower than
      that of control group at the first day of re-feeding, it increased significantly
      higher than that of control group by day 14 (P <0.05). During the starvation
      period, expression of IGF-1 mRNA in liver decreased, but it was not statistically
      different from that of the control group (P>0.05). During the early period of re
      feeding, the abundance of IGF-1 mRNA was still significantly lower than that of
      control group (P <0.05), then increased to the level of control group on day 7.
      IGF-1R mRNA showed a decreasing trend after starvation, and reached a
      significantly low value on day 3 (P <0.05). After re-feeding, the abundance of
      IGF-1R mRNA increased to peak at day 14. These results indicate that the higher
      level of IGFBP-1 in serum and IGF-1R mRNA in muscle after re-feeding could
      improve the promoting growth effect of IGF-1 to participate in the regulation of
      compensatory growth.

PMID- 22653859
TI  - [Identification and expressional analysis of green fluorescent protein genes in
      amphioxus].
AB  - Endogenous green fluorescent proteins (GFPs) have recently been found in
      amphioxus, where different characteristics of light production in different
      development stages and between different individuals have manifested. We
      identified the GFP genes in an amphioxus species Branchiostoma belcheri and
      monitored real time fluorescence signals of GFPs during different developmental
      stages to provide an insight on the GFP function in amphioxus. We found there are
      at least 12 endogenous GFP genes in amphioxus genome, and fluorescent expression
      changes in body position during different developmental stages. Additionally, GFP
      expression after metamorphosis development differed significantly among different
      amphioxus individuals, suggesting that there are multiple GFP homologous genes
      responsible for fluorescent expression. Expression levels of these genes varied
      significantly during different developmental stages, indicating that different
      GFP genes may have their unique functions in the development of amphioxus during
      specific phases of growth.

PMID- 22653860
TI  - [Comparison and analysis between P(ST) and F(ST) of mitten crabs in the Minjiang
      River].
AB  - Recently, differentiation in phenotypic traits (P(ST)) and differentiation at
      neutral molecular markers (F(ST)) across populations have been become an
      important topic in evolutionary biology. The Minjiang River is a key genetic
      introgression zone between the Chinese mitten crab (Eriocheir sinensis) and the
      Hepu mitten crab (Eriocheir hepuensis), making it an excellent area to study
      their genetics and evolutionary mechanisms. We compared and analyzed P(ST) in 14
      phenotypic traits and F(ST) in six microsatellite markers from 133 individuals of
      the mitten crab, sampled in the Minjiang River in 2009 and 2010. The results
      indicated that 11 phenotypic traits were significantly different (P<0.01) between
      the 2009 and 2010 populations. The mean expected heterozygosity (H(E)) of the
      2009 populations was significantly higher (P=0.008) than that of 2010
      populations, but the mean allele richness (A(R)), observed heterozygosity (H( O))
      and inbreeding coefficient (F(IS)) were all not significant between 2009 and 2010
      populations (P=0.136-0.675). F(ST) in microsatellite markers was 0.1429 between
      the two years. In the 14 traits, only one trait (F2) was found with P(ST)<F( ST),
      suggesting that stabilizing selection is favoring a trait of F2; the other 13
      traits were P(ST)>F(ST), suggesting that directional selection is occurring. This
      study provides valuable data to the further study and analysis of the molecular
      evolution of the mitten crab, and contributes a useful reference in comparing
      P(ST) and F(ST) in other aquatic organisms.

PMID- 22653861
TI  - [Phylogenetic relationship among some groups of orthopteran based on complete
      sequences of the mitochondrial COI gene].
AB  - Complete sequences of the COI gene were used to reconstruct the phylogenetic
      relationship among 56 species from Orthoptera. We also analyzed the reliability
      of Orthoptera phylogenetic relationship using translated amino acid sequences of
      the COI genes. The COI sequences were divided into three data sets on the basis
      of different codon positions to calculate the Partitioned Bremer support (PBS),
      and to test the phylogenetic signal in different codon positions of protein
      coding genes. The result supports the monophyly of Caelifera and Ensifera; but
      the monophyly of Acrididae, Catantopidae, Oedipodidae, Arcypteridae and
      Gomphoceridae are not supported. The P-distances among families vary from 0.107
      to 0.153, which are smaller than those of other families, being consist with the
      classification that these 5 families should be merged into one family
      (Acrididae). Chrotogonidae and Pyrgomorphidae belong to the superfamily
      Pyrgomorphoidea. Pamphagidae should be a family alone consistent with Otte's
      taxonomic system. According to the PBS values, the 3rd and 1st codon positions
      contribution more for the Phylogenetic tree branches than the 2nd, and longer
      sequences contain more informative sites. We further demonstrated that it is
      feasible for phylogenetic studies at family level to use the genetic distances
      among COI sequences from different species of Orthopera.

PMID- 22653862
TI  - [Genetic diversity of Pseudosciaena polyactis in Zhoushan based on mitochondrial
      DNA D-loop region sequences].
AB  - Pseudosciaena polyactis is an economically important species of marine fish in
      China that is currently declining due to overexploitation, environmental
      pollution and related factors. Research in to the genetic structure of
      Pseudosciaena polyactis populations plays a key role in protecting and promoting
      sustainable utilization. We collected 53 individuals of Pseudosciaena polyactis
      from Zhoushan, Zhejiang and sequenced and amplified the mitochondrial DNA (mtDNA)
      D-loop region using Polymerase Chain Reactions (PCR). The sequence length of the
      53 individuals ranged from 795 to 801 bp. The sequences were analyzed by Clustal
      X1.83, MEGA3.1 and DnaSP4.0. The results showed that the average base content of
      T, C, A, G was 30.3%, 23.1%, 32.3% and 14.3%, respectively and there were 93
      transition or transversion sites, including 53 single nucleotide mutation sites
      and 40 parsimony informative sites, which accounted for 11.6% of the length of
      the analyzed sequences. In total, we identified 52 haplotypes and found haplotype
      diversity (hd) of 0.9993, average number of nucleotide differences were 9.73875
      (k), and nucleotide diversity (Pi) of 0.01233. The average genetic distance of
      haplotypes was 0.012, and the average transition/transversion was 4.305. Based on
      mitochondrial DNA D-loop region sequences, these results indicate that the
      genetic diversity of the Pseudosciaena polyactis population in Zhoushan is
      currently at a medium level.

PMID- 22653863
TI  - [Animal models of human glioma: the progress of application and investigation].
AB  - The glioma accounts for half of the central nervous tumors, among which the
      glioblastoma multiforme (GBM) is one of the most aggressive and lethal brain
      tumors. The difficulties in glioma therapy indicate the need of appropriate
      animal models for preclinical studies. Benefiting from the development of
      molecular biology, genetics, and transgenic technology, variable animal models of
      glioma have been established. These animal models of human glioma are reviewed in
      this paper.

PMID- 22653864
TI  - Distribution of serotonin and FMRF-amide in the brain of Lymnaea stagnalis with
      respect to the visual system.
AB  - Despite serotonin's and FMRF-amide's wide distribution in the nervous system of
      invertebrates and their importance as neurotransmitters, the exact roles they
      play in neuronal networks leaves many questions. We mapped the presence of
      serotonin and FMRF-amide-immunoreactivity in the central nervous system and eyes
      of the pond snail Lymnaea stagnalis and interpreted the results in connection
      with our earlier findings on the central projections of different peripheral
      nerves. Since the chemical nature of the intercellular connections in the retina
      of L. stagnalis is still largely unknown, we paid special attention to clarifying
      the role of serotonin and FMRF-amide in the visual system of this snail and
      compared our findings with those reported from other species. At least one
      serotonin- and one FMRF-amidergic fibre were labeled in each optic nerve, and
      since no cell bodies in the eye showed immunoreactivity to these
      neurotransmitters, we believe that efferent fibres with somata located in the
      central ganglia branch at the base of the eye and probably release 5HT and FMRF
      amide as neuro-hormones. Double labelling revealed retrograde transport of
      neurobiotin through the optic nerve, allowing us to conclude that the central
      pathways and serotonin- and FMRF-amide-immunoreactive cells and fibres have
      different locations in the CNS in L. stagnalis. The chemical nature of the
      fibres, which connect the two eyes in L. stagnalis, is neither serotoninergic nor
      FMRF-amidergic.

PMID- 22653865
TI  - The structure of integument and wax glands of Phenacoccus fraxinus (Hemiptera:
      Coccoidea: Pseudococcidae).
AB  - Using scanning electron microscopy and optical microscopy, we studied the
      structure of the integument and wax glands of the mealybug, Phenacoccus fraxinus
      Tang (Hemiptera: Coccoidea: Pseudococcidae). We observed the ultrastructure of
      four wax pores including trilocular, quinquelocular, and multilocular pores as
      well as tubular ducts, recording characteristics of their structure, size and
      distribution. We found that that the integument of the mealybug consists of three
      main layers-the procuticle, epidermis and basement membrane-and four sub-layers
      of the procuticle-the epicuticle, exocuticle, endocuticle and formation zone. The
      wax-secreting gland cells were closely arranged in epidermis. All of them were
      complex and composed of one central cell and two or more lateral cells. These
      complex cells possess a large common reservoir for collection and storage.
      Synthesized by the glandular cells, the wax is excreted outside integument
      through canals.

PMID- 22653866
TI  - Important population viability analysis parameters for giant pandas (Aliuropoda
      melanoleuca).
AB  - Population viability analysis (PVA) is a tool to evaluate the risk of extinction
      for endangered species and aid conservation decision-making. The quality of PVA
      output is dependent on parameters related to population dynamics and life
      history; however, it has been difficult to collect this information for the giant
      panda (Aliuropoda melanoleuca), a rare and endangered mammal native to China,
      confined to some 30 fragmented habitat patches. Since giant pandas are long
      lived, mature late, have lower reproductive rates, and show little sexual
      dimorphism, obtaining data to perform adequate PVA has been difficult. Here, we
      develop a parameter sensitivity index by modeling the dynamics of six giant panda
      populations in the Minshan Mountains, in order to determine the parameters most
      influential to giant panda populations. Our data shows that the giant panda
      populations are most sensitive to changes in four female parameters: initial
      breeding age, reproductive rate, mortality rate between age 0 and 1, and
      mortality rate of adults. The parameter sensitivity index strongly correlated
      with initial population size, as smaller populations were more sensitive to
      changes in these four variables. This model suggests that demographic parameters
      of females have more influence on the results of PVA, indicating that females may
      play a more important role in giant panda population dynamics than males.
      Consequently, reintroduction of female individuals to a small giant panda
      population should be a high priority for conservation efforts. Our findings form
      a technical basis for the coming program of giant panda reintroduction, and
      inform which parameters are crucial to successfully and feasibly monitoring wild
      giant panda populations.

PMID- 22653867
TI  - Age, growth and reproduction of Sarcocheilichthys nigripinnis from the Qingyi
      Stream in the Huangshan Mountains.
AB  - Identifying the life-history strategies of fish and their associations with the
      surrounding environment is the basic foundation in the conservation and
      sustainable utilization of fish species. We examined the age, growth, and
      reproduction of Sarcocheilichthys nigripinnis using 352 specimens collected
      monthly from May 2009 to April 2010 in the Qingyi Stream. We found the sex ratio
      of this study population was 0.58:1 (female: male), significantly different from
      expected 1:1. Females and males both comprised four age groups. The annuli on the
      scales were formed during February and March. No obvious between-sex difference
      was observed in length-weight and length-scale-radius relationships. The total
      length in back-calculation significantly increased with age for both sexes, but
      did not differ significantly at each age between the two sexes. An inflection
      point was observed in the growth curves given by the von Bertalanffy growth
      function for total weight. At this inflection point, fish were 3.95 years. Both
      sexes reach their 50% sex maturity at age 2, when females and males were 94.7 mm
      and 103.0 mm total length. The temporal pattern of the gonado-somatic index
      corresponded to a spawning period that occurred from April through July. The non
      synchronicity of egg diameter in each mature ovary during the breeding period
      suggested these fish may be batch spawners. The absolute fecundity increased
      significantly with total length and weight, whereas no significant correlation
      was observed between the relative fecundity and body size.

PMID- 22653868
TI  - Intramolecular [2+2] photocycloaddition reactions as an entry to the 2
      oxatricyclo[4.2.1.0(4,9)]nonan-3-one skeleton of lactiflorin.
AB  - Two [2+2] photocycloaddition routes were evaluated as possible ways to access the
      tricyclic core structure found in the terpene monoglycoside lactiflorin. While
      the first route via gamma-substituted cyclopentenones was quickly discarded, the
      reactions of racemic (5R*)-3-benzyloxy-5-but-3'-enyl-4-methoxycarbonylfuran-2(5H)
      ones proceeded in high yields and with perfect diastereoselectivity. However, it
      turned out that the regioselectivity was strongly dependent on the substitution
      pattern within the but-3'-enyl chain, which connects the terminal olefinic double
      bond to the photoexcited butenolide chromophor. If the chain was unsubstituted or
      if a tert-butyldimethylsilyloxy group was placed at the 2' position in a syn
      relationship to the existing stereogenic center (5R*,2'S*), the crossed product
      prevailed with regioselectivities of 89:11 to 69:31. If the tert
      butyldimethylsilyloxy group was positioned at 2' in an anti-relationship to the
      existing stereogenic center (5R*,2'R*), the desired straight products were
      obtained in regioselectivities of 74:24 to 55:45 (61-83% yield). Following this
      route, the aglycon part of lactiflorin was obtained by an intramolecular [2+2]
      photocycloaddition and a subsequent hydrogenolysis in 53% yield. Its further
      conversion into the natural product after glycosylation included a methyl
      addition to the lactone carbonyl group, which was optimized to give the desired
      key intermediate in a yield of 70%. The further conversion to lactiflorin was
      achieved in four steps and with an overall yield of 49%.

PMID- 22653869
TI  - MYC-regulated genes involved in liver cell dysplasia identified in a transgenic
      model of liver cancer.
AB  - Foci of liver cell dysplasia (LCD) are distinct morphological entities and may
      evolve into hepatocellular carcinomas (HCCs). While most HCCs overexpress c-Myc,
      its role in LCD remains uncertain. Therefore, a c-Myc transgenic model of HCC was
      investigated to understand the genetic events forcing liver cells into dysplasia
      and subsequent malignant transformation. Specifically, whole genome scans enabled
      fingerprinting of genes at different stages of disease, ie LCD and HCC, while
      laser microdissected LCD lesions were used to validate regulation of candidate
      genes by quantitative real-time RT-PCR, ie Mybbp1a, Rps7, Rps19, Rpl10a, Skp1a,
      Tfdp1, Nhp2, and Bola2. EMSA band shift assays confirmed c-Myc DNA binding at
      regulatory sequences of candidate gene-specific promoters. Additionally,
      published ChIP-seq data helped to define the candidate genes as c-Myc bona fide
      targets. Treatment of the human hepatoma cell line HepG2 with hepatic growth
      factor (Hgf) caused c-Myc protein induction and transcriptional up-regulation of
      candidate genes, albeit at different levels when individual genes were compared.
      A significant increase of HepG2 entering the G1-phase was associated with up
      regulation of the candidate genes in an Hgf concentration-dependent matter.
      Finally, we confirmed regulation of candidate genes in patients' samples with low
      and high-grade dysplasia and HCC staged T1 to T3, while their expression was
      unchanged in focal nodular hyperplasia and hepatic adenoma, therefore asserting
      the diagnostic value and clinical significance of these candidate genes. Overall,
      novel c-Myc targeted genes were identified and may contribute to hepatocyte
      transformation by altering cell cycle control, thereby contributing to c-Myc's
      oncogenic activity.

PMID- 22653870
TI  - Screening of microbial contamination and antimicrobial activity of sea cucumber
      Holothuria polii.
AB  - Microbiological studies were carried out on microbial contamination and
      antimicrobial activity of sea cucumber Holothuria polii collected from
      Mediterranean Sea at Abu-kir shore of Alexandria, Egypt. The obtained results
      revealed the presence of isolates of five human Gram-negative pathogenic
      bacteria, representing five genera were identified to species level, including,
      Esherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella sp.
      and Shigella sp. In addition, an yeast Candida albicans was isolated. The
      pathogenic bacteria were identified using API 20E strip system (BioMereux). All
      collected H. polii specimens were healthy with no external signs of infection.
      Histopathological study of the tegument, intestine and gonads showed no abnormal
      changes. The antimicrobial activity of two tegumental ethanol extracts (A and B,
      differ in the method of dehydration) were tested against wide range of pathogenic
      bacteria and fungi, including intestinal, skin and nosocomial pathogens and one
      plant fungal pathogen. The results revealed a remarkable antifungal activity of
      the extract B at 2.5 mg/ml MIC90, especially on Aspergillus niger, Scloretium sp,
      C. albicans, Aspergillus flavus and Malassezia furfur, and limited antibacterial
      activity against Gram-negative bacteria (Salmonella choleraesuis ATCC 14028 and
      Aeromonas hydrophila). The domain of bacterial and limited fungal contamination
      confirms the results that showed strong antifungal activity of investigated
      extract.

PMID- 22653871
TI  - DNA hypermethylation in somatic cells correlates with higher reprogramming
      efficiency.
AB  - The efficiency of somatic cell reprogramming to pluripotency using defined
      factors is dramatically affected by the cell type of origin. Here, we show that
      human keratinocytes, which can be reprogrammed at a higher efficiency than
      fibroblast [Nat Biotechnol 2008;26:1276-1284], share more genes hypermethylated
      at CpGs with human embryonic stem cells (ESCs) than other somatic cells
      frequently used for reprogramming. Moreover, pluripotent cells reprogrammed from
      keratinocytes (KiPS) are more similar to ESCs than those reprogrammed from
      fibroblasts (FiPS) in regard to DNA methylation levels, mostly due to the
      presence of genes that fail to acquire high levels of DNA methylation in FiPS
      cells. We propose that higher reprogramming efficiency correlates with the
      hypermethylation of tissue-specific genes rather than with a more permissive
      pluripotency gene network.

PMID- 22653872
TI  - One-pot synthesized DNA-CdTe quantum dots applied in a biosensor for the
      detection of sequence-specific oligonucleotides.

PMID- 22653873
TI  - Bioavailability of cyanide and metal-cyanide mixtures to aquatic life.
AB  - Cyanide can be toxic to aquatic organisms, and the U.S. Environmental Protection
      Agency has developed ambient water-quality criteria to protect aquatic life.
      Recent work suggests that considering free, rather than total, cyanide provides a
      more accurate measure of the biological effects of cyanides and provides a basis
      for water-quality criteria. Aquatic organisms are sensitive to free cyanide,
      although certain metals can form stable complexes and reduce the amount of free
      cyanide. As a result, total cyanide is less toxic when complexing metals are
      present. Cyanide is often present in complex effluents, which requires
      understanding how other components within these complex effluents can affect
      cyanide speciation and bioavailability. The authors have developed a model to
      predict the aqueous speciation of cyanide and have shown that this model can
      predict the toxicity of metal-cyanide complexes in terms of free cyanide in
      solutions with varying water chemistry. Toxicity endpoints based on total cyanide
      ranged over several orders of magnitude for various metal-cyanide mixtures.
      However, predicted free cyanide concentrations among these same tests described
      the observed toxicity data to within a factor of 2. Aquatic toxicity can be well
      described using free cyanide, and under certain conditions the toxicity was
      jointly described by free cyanide and elevated levels of bioavailable metals.

PMID- 22653874
TI  - Design strategy for DNA rotaxanes with a mechanically reinforced PX100 axle.

PMID- 22653876
TI  - Dosing regimen determination for juvenile idiopathic arthritis: a review of
      studies during drug development.
AB  - Juvenile idiopathic arthritis (JIA) is the most common childhood arthritis. In
      the past 10-15 years, the medical treatment options of JIA have greatly evolved
      and expanded due to a better understanding of the disease and the application of
      biologic agents. Regulations pertinent to pediatric clinical research have also
      helped provide a legal basis for investigating the effects of drugs and biologics
      in pediatrics and facilitate the pediatric drug development. The evaluation of
      clinical pharmacology, efficacy, and safety has provided valuable labeling
      information for pediatric use, including comparing exposure between adult and
      pediatric patients, bridging different formulations and regimens, providing
      appropriate dose selection recommendation with the modeling and simulation
      approach, and assessing the risks and benefits. This review summarizes the drugs
      and biologics with JIA labeling implications and discusses the application of
      clinical pharmacology, safety, and efficacy assessment in determining pediatric
      dosing regimens.

PMID- 22653875
TI  - Plasma proteomics of differential outcome to long-term therapy in children with
      idiopathic pulmonary arterial hypertension.
AB  - PURPOSE: The prognosis for children with IPAH unresponsive to therapy is poor. We
      investigated the plasma proteome for a molecular basis of good versus poor
      outcome to long-term vasodilator therapy. EXPERIMENTAL DESIGN: Plasma was
      collected at baseline or shortly after therapy initiation and following chronic
      vasodilator therapy, then divided into those with good outcome (n = 8), and those
      with a poor outcome (n = 7). To identify proteins unique to either outcome, we
      used differential gel electrophoresis and mass spectrometry. Results were
      confirmed by commercial enzyme-linked immunosorbent assay. RESULTS: Before and
      after therapy, SAA-4 was 4-fold lower in those with good outcome compared to
      those with poor outcome, while serum paraoxonase/arylesterase-1 was increased 2
      fold in those with good outcome versus poor outcome. After therapy, haptoglobin
      and hemopexin were 1.45- and 1.8-fold lower, respectively, in those with a good
      versus poor outcome. Among those with a good outcome, SAP was 1.3-fold lower
      prior to therapy. CONCLUSIONS AND CLINICAL RELEVANCE: SAP and SAA-4 regulate
      circulating mononuclear phagocytes. As such, they may contribute to the
      differential response to chronic vasodilator therapy in the context of
      inflammation in IPAH.

PMID- 22653877
TI  - Intestinal transport of aminopterin enantiomers in dogs and humans with psoriasis
      is stereoselective: evidence for a mechanism involving the proton-coupled folate
      transporter.
AB  - N-[4-[[(2,4-diamino-6-pterdinyl)methyl]amino]benzoyl]-L/D-glutamic acid (L/D-AMT)
      is an investigational drug in phase 1 clinical development that consists of the L
      and D-enantiomers of aminopterin (AMT). L/D-AMT is obtained from a novel process
      for making the L-enantiomer (L-AMT), a potent oral antiinflammatory agent. The
      purpose of these studies was to characterize oral uptake and safety in the dog
      and human of each enantiomer alone and in combination and provide in vitro
      evidence for a mechanism of intestinal absorption. This is the first report of L
      /D-AMT in humans. In dogs (n = 40) orally dosed with L-AMT or D-AMT absorption
      was stereoselective for the L-enantiomer (6- to 12-fold larger peak plasma
      concentration after oral administration and area under the plasma concentration
      time curve at 0-4 h; p < 0.001). D-AMT was not toxic at the maximal dose tested
      (82.5 mg/kg), which was 100-fold larger than the maximal nonlethal L-AMT dose
      (0.8 mg/kg). Dogs (n = 10) and humans with psoriasis (n = 21) orally administered
      L-AMT and L /D-AMT at the same L-enantiomer dose resulted in stereoselective
      absorption (absent D-enantiomer in plasma), bioequivalent L-enantiomer
      pharmacokinetics, and equivalent safety. Thus, the D-enantiomer in L/D-AMT did
      not perturb L-enantiomer absorption or alter the safety of L-AMT. In vitro uptake
      by the human proton-coupled folate transporter (PCFT) demonstrated minimal
      transport of D-AMT compared with L-AMT, mirroring the in vivo findings.
      Enantiomer selectivity by PCFT was attributable almost entirely to decreased
      binding affinity rather than changes in transport rate. Collectively, our results
      demonstrate a strong in vitro-in vivo correlation implicating stereoselective
      transport by PCFT as the mechanism underlying stereoselective absorption observed
      in vivo.

PMID- 22653879
TI  - Two Vernier-templated routes to a 24-porphyrin nanoring.

PMID- 22653878
TI  - Hormonal and chemical regulation of paraoxonases in mice.
AB  - In humans and rodents, paraoxonase (PON/Pon) 1 expression and activity in livers
      and serum are higher in females than in males, and some drugs increase
      paraoxonase's expression. However, the underlining mechanisms of gender-divergent
      expression and chemical regulation of Pon1 remain largely unknown. The present
      study determined the regulatory mechanisms contributing to gender-divergent and
      chemically altered Pon expression in mouse livers. Pon1 mRNA was much more
      abundant in the livers of mice than other tissues, with higher levels in female
      livers than male livers at mRNA and protein levels. Pon2 mRNA was ubiquitously
      expressed in mouse tissues, but minimally in mouse liver. Pon3 mRNA was most
      abundant in mouse lung and liver and less abundant in other tissues. Pon1 mRNA
      was lowest in fetal liver, markedly increased at parturition, and remained
      relatively constant thereafter. Pon2 and Pon3 mRNA are highly expressed in fetal
      liver and decreased after birth. Male-pattern growth hormone (GH) administration
      in hypophysectomized and lit/lit mice decreased Pon1 expression. Sex hormones and
      female-pattern GH administration had no effect on Pon1 expression, indicating the
      importance of male-pattern GH in regulating Pon1. Aryl hydrocarbon receptor,
      pregnane X receptor, and NF-E2-related factor activators had no effect on Pon1
      mRNA. A constitutive androstane receptor (CAR) activator decreased Pon1
      expression in wild-type but not CAR-null mice. In conclusion, Pon1 mRNA was most
      abundant in adult mouse livers, whereas Pon2 and Pon3 mRNAs were most abundant in
      fetal mouse livers. Female-predominant Pon1 expression in mouse livers is caused
      by the inhibitory effects of male-pattern GH secretion, and CAR activation
      decreases Pon1 expression.

PMID- 22653880
TI  - Cross-cultural adaptation and validation of the Peripheral Artery Questionnaire:
      Korean version for patients with peripheral vascular diseases.
AB  - The Peripheral Artery Questionnaire (PAQ), as developed in US English, is a
      validated scale to evaluate the health status of patients with peripheral artery
      disease (PAD). The aim of this study was to translate the PAQ into Korean and to
      evaluate its reliability and validity. A multi-step process of forward
      translation, reconciliation, consultation with the developer, back-translation
      and proofreading was conducted. The test-retest reliability was evaluated at a 2
      week interval using the intra-class correlation coefficient (ICC). The validity
      was assessed by identifying associations between Korean PAQ (KPAQ) scores and
      Korean Health Assessment Questionnaire (KHAQ) scores. A total of 100 PAD patients
      were enrolled: 63 without and 37 with severe claudication. The reliability of the
      KPAQ was adequate, with an ICC of 0.71. There were strong correlations between
      KPAQ's subscales. Cronbach's alpha for the summary score was 0.94, indicating
      good internal consistency and congruence with the original US version. The
      validity was supported by a significant correlation between the total KHAQ score
      and KPAQ physical function, stability, symptom, social limitation and quality of
      life scores (r = -0.24 to -0.90; p < 0.001) as well as between the KHAQ walking
      subscale and the KPAQ physical function score (r = -0.55, p < 0.001). Our results
      indicate that the KPAQ is a reliable, valid instrument to evaluate the health
      status of Korean patients with PAD.

PMID- 22653881
TI  - The unpredictability of electrostatic charging.
AB  - Capricious charges: the electrostatic charging that occurs when two surfaces come
      into contact is familiar to everyone, and has been known for millennia.
      Nonetheless, the scientific understanding of the phenomenon is poor, and it is
      not possible to reliably predict which surface will charge positively and which
      will charge negatively. Recent work shows why electrostatic charging may never be
      predictable.

PMID- 22653883
TI  - Exploration of forbidden Povarov processes as a source of unexpected reactivity:
      a multicomponent Mannich-Ritter transformation.
AB  - When a door closes, a window opens! The use of geometrically or electronically
      restricted imines for Povarov-type processes does not afford the anti-Bredt
      tetrahydroquinolines, but leads instead to highly functionalized structures
      through novel reaction pathways (see picture; LA=Lewis acid). The exploration of
      "forbidden" routes constitutes a valuable approach in the search for new
      multicomponent reactions.

PMID- 22653882
TI  - Independent factors and predictive score for extrahepatic metastasis of
      hepatocellular carcinoma following curative hepatectomy.
AB  - BACKGROUND: Postoperative extrahepatic metastasis (EHM) contributes to a poor
      prognosis in patients with hepatocellular carcinoma (HCC) after hepatectomy. This
      study was aimed to develop a practical method that can be used to predict
      postoperative EHM. METHODS: In total, 578 patients were enrolled. We analyzed the
      clinicopathological features of the tumors and did a long-term follow-up to
      observe HCC recurrence. Postoperative EHM was detected in 136 patients, and
      multivariate analysis was used to confirm independent risk factors for
      postoperative EHM. After the factors were identified, a predictive scoring system
      was constructed as a weighted sum of these factors. The cutoff value that
      determines a high risk for EHM was defined by maximizing the Youden's index of
      the receiver operating characteristic curve. RESULTS: Microvascular invasion,
      incomplete capsule, and larger tumor diameter were the three independent factors
      predictive for a high risk for EHM. The scoring system was derived with an area
      under the curve (AUC) of 0.81 for postoperative 10-year EHM prediction. A cutoff
      value of 43 was derived and validated with a sensitivity >90% and specificity
      >60% to predict the development of EHM. This system was further verified in a
      subgroup of Barcelona Clinic Liver Cancer stage 0-A patients with an AUC of 0.82.
      When the cutoff value was set at 43, the sensitivity and specificity were 90.38%
      and 64.88%, respectively. CONCLUSIONS: Our predictive scoring system may be used
      to identify HCC patients who have a high risk for EHM following curative
      hepatectomy.

PMID- 22653884
TI  - Human rabies in Tianjin, China.
AB  - BACKGROUND: Human rabies has recently re-emerged as a significant public health
      threat in Tianjin, China. METHODS: Using surveillance data compiled by the
      Tianjin Centers for Disease Control and Prevention, we describe 60 cases of human
      rabies reported from 2005 to 2011 in the municipality of Tianjin, China. RESULTS:
      All 60 cases of human rabies resulted in death. Cases were primarily male (80%),
      middle aged (mean 40.6 years), and exposed to rabies in a rural setting (82%).
      Most exposures were associated with dog bites (93%) and no animal had a history
      of rabies vaccination; no cases were laboratory confirmed. Fifteen percent of
      patients sought medical attention for their wound, and none received a complete
      regimen of WHO-recommended post-exposure prophylaxis (PEP). CONCLUSIONS: These
      findings suggest the need for China's public health authority to improve animal
      rabies surveillance and control strategies through laboratory case confirmation,
      more rapid response to potential exposures with provision of appropriate PEP, and
      education to the public and to health care providers on identifying and reducing
      rabies risk.

PMID- 22653885
TI  - The effects of a community-based partnership, Project Access Dallas (PAD), on
      emergency department utilization and costs among the uninsured.
AB  - BACKGROUND: Approximately 19% of non-elderly adults are without health insurance.
      The uninsured frequently lack a source of primary care and are more likely to use
      the emergency department (ED) for routine care. Improving access to primary care
      for the uninsured is one strategy to reduce ED overutilization and related costs.
      METHODS: A comparison group quasi-experimental design was used to evaluate a
      broad-based community partnership that provided access to care for the uninsured
      Project Access Dallas (PAD)-on ED utilization and related costs. Eligible
      uninsured patients seen in the ED were enrolled in PAD (n = 265) with similar
      patients not enrolled in PAD (n = 309) serving as controls. Study patients were
      aged 18-65 years, <200% of the federal poverty level and uninsured. Outcome
      measures include the number of ED visits, hospital days and direct and indirect
      costs. RESULTS: PAD program enrollees had significantly fewer ED visits (0.93 vs.
      1.44; P < 0.01) and fewer inpatient hospital days (0.37 vs. 1.07; P < 0.05) than
      controls. Direct hospital costs were ~60% less ($1188 vs. $446; P < 0.01) and
      indirect costs were 50% less ($313 vs. $692; P < 0.01). CONCLUSIONS: A broad
      based community partnership program can significantly reduce ED utilization and
      related costs among the uninsured.

PMID- 22653886
TI  - Trends in hospital admissions for sickle cell disease in England, 2001/02
      2009/10.
AB  - BACKGROUND: Sickle cell disease (SCD) is a rising cause of mortality and
      morbidity in England and consequently an important policy issue for the National
      Health Service. There has been no previous study that has examined SCD admission
      rates in England. METHODS: Data from Hospital Episode Statistics were analysed
      for all hospital episodes (2001/10) in England with a primary diagnosis of sickle
      cell anaemia with crisis (D57.0) or without crisis (D57.1). Secondary and
      tertiary diagnoses were examined among those patients admitted with either of
      these codes as their primary diagnosis. RESULTS: The overall SCD admission rate
      per 100 000 has risen from 21.2 in 2001/02 to 33.5 in 2009/10, a rise of over
      50%. London accounts for 74.9% of all SCD admissions in England. 57.9% of
      patients admitted are discharged within 24 h. The largest rise in admission rates
      was seen among males aged 40-49 years where admission rates per 100 000 increased
      from 7.6 to 26.8 over the study period. CONCLUSIONS: Our data show that SCD
      admissions are rising in England, particularly in London. Over half of patients
      admitted with SCD were discharged within 24 h, suggesting that some of these
      admissions could be prevented through better ambulatory care of patients.

PMID- 22653887
TI  - Cellular requirements for LARK in the Drosophila circadian system.
AB  - RNA-binding proteins mediate posttranscriptional functions in the circadian
      systems of multiple species. A conserved RNA recognition motif (RRM) protein
      encoded by the lark gene is postulated to serve circadian output and molecular
      oscillator functions in Drosophila and mammals, respectively. In no species,
      however, has LARK been eliminated, in vivo, to determine the consequences for
      circadian timing. The present study utilized RNA interference (RNAi) techniques
      in Drosophila to decrease LARK levels in clock neurons and other cell types in
      order to evaluate the circadian functions of the protein. Knockdown of LARK in
      timeless (TIM)- or pigment dispersing factor (PDF)-containing clock cells caused
      a significant number of flies to exhibit arrhythmic locomotor activity,
      demonstrating a requirement for the protein in pacemaker cells. There was no
      obvious effect on PER protein cycling in lark interference (RNAi) flies, but a
      knockdown within the PDF neurons was associated with increased PDF
      immunoreactivity at the dorsal termini of the small ventral lateral neuronal (s
      LNv) projections, suggesting an effect on neuropeptide release. The expression of
      lark RNAi in multiple neurosecretory cell populations demonstrated that LARK is
      required within pacemaker and nonpacemaker cells for the manifestation of normal
      locomotor activity rhythms. Interestingly, decreased LARK function in the
      prothoracic gland (PG), a peripheral organ containing a clock required for the
      circadian control of eclosion, was associated with weak population eclosion
      rhythms or arrhythmicity.

PMID- 22653888
TI  - Solitary and gregarious locusts differ in circadian rhythmicity of a visual
      output neuron.
AB  - Locusts demonstrate remarkable phenotypic plasticity driven by changes in
      population density. This density dependent phase polyphenism is associated with
      many physiological, behavioral, and morphological changes, including observations
      that cryptic solitarious (solitary-reared) individuals start to fly at dusk,
      whereas gregarious (crowd-reared) individuals are day-active. We have recorded
      for 24-36 h, from an identified visual output neuron, the descending
      contralateral movement detector (DCMD) of Schistocerca gregaria in solitarious
      and gregarious animals. DCMD signals impending collision and participates in
      flight avoidance maneuvers. The strength of DCMD's response to looming stimuli,
      characterized by the number of evoked spikes and peak firing rate, varies
      approximately sinusoidally with a period close to 24 h under constant light in
      solitarious locusts. In gregarious individuals the 24-h pattern is more complex,
      being modified by secondary ultradian rhythms. DCMD's strongest responses occur
      around expected dusk in solitarious locusts but up to 6 h earlier in gregarious
      locusts, matching the times of day at which locusts of each type are most active.
      We thus demonstrate a neuronal correlate of a temporal shift in behavior that is
      observed in gregarious locusts. Our ability to alter the nature of a circadian
      rhythm by manipulating the rearing density of locusts under identical light-dark
      cycles may provide important tools to investigate further the mechanisms
      underlying diurnal rhythmicity.

PMID- 22653889
TI  - Is the sex communication of two pyralid moths, Plodia interpunctella and Ephestia
      kuehniella, under circadian clock regulation?
AB  - Females of the Indian meal moth, Plodia interpunctella, and females of the
      Mediterranean flour month, Ephestia kuehniella (both Lepidoptera: Pyralidae),
      exhibit daily rhythms in calling behavior. The peak in P. interpunctella calling
      occurs at dusk, whereas E. kuehniella calls preferentially at dawn. This behavior
      turned arrhythmic in P. interpunctella females in constant darkness (DD) and
      remained arrhythmic in constant light (LL), whereas E. kuehniella females showed
      a persistent rhythm in DD and suppression of the behavior in LL, indicating
      regulation by a circadian clock mechanism. The rhythm of male locomotor activity
      corresponded well with the sexual activity of females, reaching the peak at dusk
      in P. interpunctella and at dawn in E. kuehniella. An immunohistochemical study
      of the pheromone biosynthesis activating neuropeptide, corazonin, and pigment
      dispersing factor revealed distinct sets of neurons in the brain-subesophageal
      complex and in the neurohemal organs of the 2 species.

PMID- 22653890
TI  - The colony environment, but not direct contact with conspecifics, influences the
      development of circadian rhythms in honey bees.
AB  - Honey bee (Apis mellifera) workers emerge from the pupae with no circadian
      rhythms in behavior or brain clock gene expression but show strong rhythms later
      in life. This postembryonic development of circadian rhythms is reminiscent of
      that of infants of humans and other primates but contrasts with most insects,
      which typically emerge from the pupae with strong circadian rhythms. Very little
      is known about the internal and external factors regulating the ontogeny of
      circadian rhythms in bees or in other animals. We tested the hypothesis that the
      environment during early life influences the later expression of circadian
      rhythms in locomotor activity in young honey bees. We reared newly emerged bees
      in various social environments, transferred them to individual cages in constant
      laboratory conditions, and monitored their locomotor activity. We found that the
      percentage of rhythmic individuals among bees that experienced the colony
      environment for their first 48 h of adult life was similar to that of older
      sister foragers, but their rhythms were weaker. Sister bees isolated individually
      in the laboratory for the same period were significantly less likely to show
      circadian rhythms in locomotor activity. Bees experiencing the colony environment
      for only 24 h, or staying for 48 h with 30 same-age sister bees in the
      laboratory, were similar to bees individually isolated in the laboratory. By
      contrast, bees that were caged individually or in groups in single- or double
      mesh enclosures inside a field colony were as likely to exhibit circadian rhythms
      as their sisters that were freely moving in the same colony. These findings
      suggest that the development of the circadian system in young adult honey bees is
      faster in the colony than in isolation. Direct contact with the queen, workers,
      or the brood, contact pheromones, and trophallaxis, which are all important means
      of communication in honey bees, cannot account for the influence of the colony
      environment, since they were all withheld from the bees in the double-mesh
      enclosures. Our results suggest that volatile pheromones, the colony
      microenvironment, or both influence the ontogeny of circadian rhythms in honey
      bees.

PMID- 22653891
TI  - Light acts on the zebrafish circadian clock to suppress rhythmic mitosis and cell
      proliferation.
AB  - A fundamental role of the circadian clock is to control biochemical and
      physiological processes such that they occur an optimal time of day. One of the
      most significant clock outputs from a clinical as well as basic biological
      standpoint is the timing of the cell cycle. Here we show that the circadian clock
      regulates the timing of mitosis in a light-responsive, clock-containing zebrafish
      cell line. Disrupting clock function, using a CLOCK1 dominant-negative construct
      or constant light, blocks the gating of cell division, demonstrating that this
      mitotic rhythm is cell autonomous and under control of the circadian pacemaker.
      Quantitative PCR reveals that several key mitotic genes, including Cyclin B1,
      Cyclin B2, and cdc2, are rhythmically expressed and clock-controlled. Peak
      expression of these genes occurs at a critical phase required to gate mitosis to
      the late night/early morning. Using clock and cell cycle luminescent reporter
      zebrafish cell lines, we show that light strongly represses not only circadian
      clock function, but also mitotic gene expression, and consequently slows cell
      proliferation.

PMID- 22653892
TI  - The circadian clock modulates enamel development.
AB  - Fully mature enamel is about 98% mineral by weight. While mineral crystals appear
      very early during its formative phase, the newly secreted enamel is a soft gel
      like matrix containing several enamel matrix proteins of which the most abundant
      is amelogenin (Amelx). Histological analysis of mineralized dental enamel reveals
      markings called cross-striations associated with daily increments of enamel
      formation, as evidenced by injections of labeling dyes at known time intervals.
      The daily incremental growth of enamel has led to the hypothesis that the
      circadian clock might be involved in the regulation of enamel development. To
      identify daily rhythms of clock genes and Amelx, we subjected murine ameloblast
      cells to serum synchronization to analyze the expression of the circadian
      transcription factors Per2 and Bmal1 by real-time PCR. Results indicate that
      these key genetic regulators of the circadian clock are expressed in synchronized
      murine ameloblast cell cultures and that their expression profile follows a
      circadian pattern with acrophase and bathyphase for both gene transcripts in
      antiphase. Immunohistological analysis confirms the protein expression of Bmal
      and Cry in enamel cells. Amelx expression in 2-day postnatal mouse molars
      dissected every 4 hours for a duration of 48 hours oscillated with an
      approximately 24-hour period, with a significant approximately 2-fold decrease in
      expression during the dark period compared to the light period. The expression of
      genes involved in bicarbonate production (Car2) and transport (Slc4a4), as well
      as in enamel matrix endocytosis (Lamp1), was greater during the dark period,
      indicating that ameloblasts express these proteins when Amelx expression is at
      the nadir. The human and mouse Amelx genes each contain a single nonconserved E
      box element within 10 kb upstream of their respective transcription start sites.
      We also found that within 2 kb of the transcription start site of the human NFYA
      gene, which encodes a positive regulator of amelogenin, there is an E-box element
      that is conserved in rodents and other mammals. Moreover, we found that Nfya
      expression in serum-synchronized murine ameloblasts oscillated with a strong 24
      hour rhythm. Taken together, our data support the hypothesis that the circadian
      clock temporally regulates enamel development.

PMID- 22653893
TI  - Enhancement and suppression of ultradian and circadian rhythms across the female
      hamster reproductive cycle.
AB  - The impact of ovarian hormones on hamster ultradian rhythms (URs) is unknown. We
      concurrently monitored URs and circadian rhythms (CRs) of home cage locomotor
      activity during the estrous cycle, pregnancy, and lactation of Syrian hamsters.
      URs with a mean period of 4-5 h were evident during the dark phase in more than
      90% of females on days 1 and 2 of the estrous cycle but were significantly less
      prevalent on cycle days 3 and 4. The period of the UR did not vary as a function
      of estrous cycle stage, but at all stages, the UR period was longer in the dark
      than the light phase. The UR acrophase occurred significantly earlier on cycle
      day 4 than on days 1 and 2, and UR robustness and amplitude were reduced on days
      3 and 4. Robustness, mesor, and amplitude of CRs were greater during cycle days 3
      and 4; timing of the CR acrophase was delayed on day 4 relative to all other
      cycle days. Effects of the estrous cycle on URs were evident only during the dark
      phase. The proportion of hamsters displaying dark phase URs increased
      significantly during early and late gestation and decreased during lactation.
      Pregnancy significantly increased UR complexity, robustness, and amplitude. The
      emergence of URs over gestation was paralleled by decrements in the robustness
      and amplitude of CRs, which also were absent in a significant proportion of dams
      during lactation but re-emerged at weaning of litters. The changing endocrine
      profile of the estrous cycle, hormonal dynamics of pregnancy and lactation, and
      nursing demands placed on dams are each associated with alterations in the
      expression of ultradian and circadian locomotor rhythms. Diminution of CRs and
      augmentation of URs may afford greater behavioral flexibility during life stages
      when interactions with mates and offspring are less predictable.

PMID- 22653894
TI  - Does pupil constriction under blue and green monochromatic light exposure change
      with age?
AB  - Many nonvisual functions are regulated by light through a photoreceptive system
      involving melanopsin-expressing retinal ganglion cells that are maximally
      sensitive to blue light. Several studies have suggested that the ability of light
      to modulate circadian entrainment and to induce acute effects on melatonin
      secretion, subjective alertness, and gene expression decreases during aging,
      particularly for blue light. This could contribute to the documented changes in
      sleep and circadian regulatory processes with aging. However, age-related
      modification in the impact of light on steady-state pupil constriction, which
      regulates the amount of light reaching the retina, is not demonstrated. We
      measured pupil size in 16 young (22.8+/-4 years) and 14 older (61+/-4.4 years)
      healthy subjects during 45-second exposures to blue (480 nm) and green (550 nm)
      monochromatic lights at low (7*10(12) photons/cm2/s), medium (3*10(13)
      photons/cm2/s), and high (10(14) photons/cm2/s) irradiance levels. Results showed
      that young subjects had consistently larger pupils than older subjects for dark
      adaptation and during all light exposures. Steady-state pupil constriction was
      greater under blue than green light exposure in both age groups and increased
      with increasing irradiance. Surprisingly, when expressed in relation to baseline
      pupil size, no significant age-related differences were observed in pupil
      constriction. The observed reduction in pupil size in older individuals, both in
      darkness and during light exposure, may reduce retinal illumination and
      consequently affect nonvisual responses to light. The absence of a significant
      difference between age groups for relative steady-state pupil constriction
      suggests that other factors such as tonic, sympathetic control of pupil dilation,
      rather than light sensitivity per se, account for the observed age difference in
      pupil size regulation. Compared to other nonvisual functions, the light
      sensitivity of steady-state pupil constriction appears to remain relatively
      intact and is not profoundly altered by age.

PMID- 22653895
TI  - Self-healing supramolecular gels formed by crown ether based host-guest
      interactions.
AB  - Automatic repair: a polymer with pendent dibenzo[24]crown-8 units (purple in
      picture) was cross-linked by two bisammonium salts (green) to form two
      supramolecular gels based on host-guest interactions. These two gels are stimuli
      responsive materials that respond to changes of the pH value and are also self
      healing materials, as can be seen by eye and as evidenced by rheological data.

PMID- 22653896
TI  - Photodynamic therapy in melanoma--an update.
AB  - Melanoma, a cancer that arises from melanocytes is one of the most unresponsive
      cancers to known therapies. Several studies showed encouraging results of the
      efficacy of photodynamic therapy (PDT) using different experimental settings in
      vitro and in vivo as well as a few clinical reports, suggesting a possible role
      as an adjuvant therapy in the management of advanced melanoma (stage III and IV).
      In experimental settings, PDT using different protocols on human and mice
      melanoma cells induced significant apoptosis, necrosis, tumor growth arrest and
      prolonged the survival of the animals, but seldom achieved complete remission
      and/or was followed by recurrence and side effects. Clinical reports showed
      regression of choroidal melanoma and skin melanoma metastasis following PDT. PDT
      consists in administration of a photosensitizer, which undergoes excitation after
      suitable irradiation emitted from a light source and generates singlet oxygen
      (1O2) and other cytotoxic oxygen species such as superoxide anion radical (O2.-)
      and hydroxyl radical (OH.). The antitumor effects result from the combination of
      direct tumor cell photodamage, destruction of tumor vasculature and activation of
      an immune response. To increase the effectiveness of PDT in melanoma, the therapy
      has to overcome the protective mechanisms like pigmentation and increased
      oxidative stress defense, possibly through inhibition of melanogenesis and
      melanosome targeted photosensitizers. The optimal protocols for tumor and
      vascular targeted PDT could destroy melanoma and endothelial tumor cells and
      activate the immune response, thus increasing the overall efficacy. Combination
      of PDT with immune stimulation therapies might increase the efficiency in
      destroying the initial tumor as well as micro metastases and decrease the
      melanoma relapses.

PMID- 22653897
TI  - Effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on rat
      vascular smooth muscle in vitro--the role of the endothelium.
AB  - Hypotension is a frequent side effect of the antidepressant treatment. It is
      controversial whether this effect is attributable to interactions within the
      central nervous or the cardiovascular system. We examined often used
      antidepressants for their vasoactive properties in vitro in rat aortal rings with
      and without endothelium. The influence of pre-incubation with the antidepressants
      (0.5 MUM) on adrenergic elicited smooth muscle contraction and the effects of
      cumulative concentrations (0.05 MUM-500 MUM) of the antidepressants on isometric
      tension were measured. In addition, conceivable modulation of the NO-cGMP,
      adrenergic and potassium channel pathways were examined. Amitriptyline and
      fluoxetine inhibited, whereas tranylcypromine enhanced adrenergic elicited
      responses of smooth muscle contraction. The antidepressants amitriptyline,
      fluoxetine and tranylcypromine showed, to a different extent, vasorelaxing
      properties in the preparations pre-contracted with phenylephrine 0.1 MUM; the
      pEC50, (means and S.E.M.) in descending order of potency: amitriptyline 6.98
      (0.13), fluoxetine 6.11 (0.05), tranylcypromine 5.33 (0.05) (n=8 each,
      preparations with endothelium); or after pre-contraction with KCl 20 mM:
      fluoxetine 6.00 (0.06), tranylcypromine 4.99 (0.30), amitriptyline, 4.89 (0.11),
      (n=7 each, preparations with endothelium). Venlafaxine did not relax the aortal
      rings and even lead to further contraction of the endothelium intact
      preparations. The observed effects were partially endothelium dependent via
      activation of the NO-cGMP pathway and some probably mediated through K+ channel
      activation. Amitriptyline, fluoxetine and tranylcypromine relax rat aorta in
      vitro. They partially delay vascular smooth muscle reactions to adrenergic
      agonists and can lead to sustained hypotension episodes despite administration of
      sympathomimetic drugs.

PMID- 22653898
TI  - Perifocal and remote blood-brain barrier disruption in cortical photothrombotic
      ischemic lesion and its modulation by the choice of anesthesia.
AB  - We assessed blood-brain barrier (BBB) disruption in early stage of
      photothrombotic focal cerebral ischemia in the rat. We specifically looked for
      contralateral changes in BBB permeability and tested the influence of two
      anesthetics on the results. Adult Wistar rats were randomly anesthetized with
      pentobarbital (PB) or ketamine-xylazine (KX). Rats received intravenously (i.v.)
      Rose Bengal followed by Evans Blue (EB). Stereotactically defined spots on
      denuded skull were irradiated by laser (532 nm) for 18 min. Twenty four hours
      later, rats were killed, brains perfused, fixated, sectioned and slices analyzed
      by fluorescence microscopy. Volume of necrosis and volume of EB-albumin
      extravasation were calculated. Evidence of BBB breakdown in remote brain areas
      was sought and compared to sham handled controls. BBB disruption was consistently
      present, frequently with EB-albumin accumulating cells. Total lesion volume did
      not significantly differ among groups (TLVPB=9.4+/-1.3 mm3 vs. TLVKX=8.3+/-2.1
      mm3); same was true for the volume of necrosis (NVPB=5.1+/-0.7 mm3 vs. NVKX=6.3+/
      1.9 mm3). However, volume of EB-albumin extravasation area was significantly
      smaller in KX group (EBEVPB=4.3+/-0.8 mm3 vs. EBEVKX=2.0+/-0.5 mm3; p=0.0293).
      Median background EB-fluorescence signal density was higher in PB group
      (p<0.0001). Furthermore, regional increase in EB-fluorescence was found in two
      animals in PB group. Our study shows that anesthesia with NMDA-antagonist
      ketamine and alpha2-adrenergic agonist xylazine may reduce BBB breakdown in
      photothrombosis. Pentobarbital anesthesia lead to increased BBB permeability in
      the contralateral hemisphere.

PMID- 22653899
TI  - The clinical aspects of Helicobacter heilmannii infection in children with
      dyspeptic symptoms.
AB  - Helicobacter heilmannii (H. heilmannii) infection is a relatively rare causative
      agent of gastroduodenal diseases in children. However, H. heilmannii frequently
      colonizes gastric mucosa of animals, mainly cats and dogs, from where it can be
      transmitted to humans. The aim of the study was to evaluate the incidence of H.
      heilmannii infection in children with dyspeptic symptoms treated in our clinic. A
      number of 13,124 esophagogastroduodenoscopies in children aged 4 to 18 years were
      conducted from 1992 to 2010. The indications for examination were: chronic
      abdominal pain, nausea, vomiting, heartburn, anaemia, disturbances of intestinal
      absorption and other. In 11,023 cases microbiologic studies and cultures toward
      Helicobacter infection were carried out and in 22 children H. heilmannii
      infection was confirmed. H. heilmannii infection was diagnosed based on
      morphologic examination in direct microscopy of biopsy specimens from gastric
      mucosa. In children with H. heilmannii infection clinical symptoms, contact with
      animals, endoscopic findings of the upper gastrointestinal tract and results of
      diagnostic tests for Helicobacter pylori infection were assessed. In our studies
      H. heilmannii infection was diagnosed in 22 children. The rate of H. heilmannii
      infection was 0.2% in examination of gastric mucosa specimens. No sex-dependent
      difference in the rates was observed. Most of the children lived in cities and
      54.5% had contact with dogs and/or cats. Children complained of chronic
      epigastric pain, nausea, vomiting and heartburn. Endoscopic studies most often
      revealed nodular gastritis and gastric or duodenal ulcer in two children. In
      three children result of the endoscopic study was normal. CONCLUSIONS: H.
      heilmannii infection in children is rare. However, it may be one of the causes of
      gastroduodenal diseases in children.

PMID- 22653900
TI  - Rebamipide attenuates nonsteroidal anti-inflammatory drugs (NSAID) induced lipid
      peroxidation by the manganese superoxide dismutase (MnSOD) overexpression in
      gastrointestinal epithelial cells.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) often cause gastrointestinal
      complications such as gastric ulcers and erosions. Recent studies on the
      pathogenesis have revealed that NSAIDs induce lipid peroxidation in gastric
      epithelial cells by generating superoxide anion in mitochondria, independently
      with cyclooxygenase-inhibition and the subsequent prostaglandin deficiency.
      Although not clearly elucidated, the impairment of mitochondrial oxidative
      phosphorylation, or uncoupling, by NSAIDs is associated with the generation of
      superoxide anion. Physiologically, superoxide is immediately transformed into
      hydrogen peroxide and diatomic oxygen with manganese superoxide dismutase
      (MnSOD). Rebamipide is an antiulcer agent that showed protective effects against
      NSAID-induced lipid peroxidation in gastrointestinal tracts. We hypothesized that
      rebamipide may attenuate lipid peroxidation by increasing the expression of MnSOD
      protein in mitochondria and decreasing the leakage of superoxide anion in NSAID
      treated gastric and small intestinal epithelial cells. Firstly, to examine
      rebamipide increases the expression of MnSOD proteins in mitochondria of
      gastrointestinal epithelial cells, we underwent Western blotting analysis against
      anti-MnSOD antibody in gastric RGM1 cells and small intestinal IEC6 cells.
      Secondly, to examine whether the pretreatment of rebamipide decreases NSAID
      induced mitochondrial impairment and lipid peroxidation, we treated these cells
      with NSAIDs with or without rebamipide pretreatment, and examined with specific
      fluorescent indicators. Finally, to examine whether pretreatment of rebamipide
      attenuates NSAID-induced superoxide anion leakage from mitochondria, we examined
      the mitochondria from indomethacin-treated RGM1 cells with electron spin
      resonance (ESR) spectroscopy using a specific spin-trapping reagent, CYPMPO.
      Rebamipide increased the expression of MnSOD protein, and attenuated NSAID
      induced mitochondrial impairment and lipid peroxidation in RGM1 and IEC6 cells.
      The pretreatment of rebamipide significantly decreased the signal intensity of
      superoxide anion from the mitochondria. We conclude that rebamipide attenuates
      lipid peroxidation by increasing the expression of MnSOD protein and decreasing
      superoxide anion leakage from mitochondria in both gastric and small intestinal
      epithelial cells.

PMID- 22653901
TI  - Interaction between selective cyclooxygenase inhibitors and capsaicin-sensitive
      afferent sensory nerves in pathogenesis of stress-induced gastric lesions. Role
      of oxidative stress.
AB  - Gastric microcirculation plays an important role in the maintenance of the
      mucosal gastric integrity and the mechanism of injury as well as providing
      protection to the gastric mucosa. Disturbances in the blood perfusion, through
      the microcapillaries within the gastric mucosa may result in the formation of
      mucosal damage. Acute gastric mucosal lesions constitute an important clinical
      problem. Originally, one of the essential component of maintaining the gastric
      mucosal integrity was the biosynthesis of prostaglandins (PGs), an issue that has
      captured the attention of numerous investigations. PGs form due to the activity
      of cyclooxygenase (COX), an enzyme which is divided into 2 isoforms: constitutive
      (COX-1) and inducible (COX-2) ones. The inhibition of COX-1 by SC-560, or COX-2
      by rofecoxib, reduces gastric blood flow (GBF) and impairs gastric mucosal
      integrity. Another detrimental effect on the gastric mucosal barrier results from
      the ablation of sensory afferent nerves by neurotoxic doses of capsaicin.
      Functional ablation of the sensory afferent nerves by capsaicin attenuates GBF
      and also renders the gastric mucosa more susceptible to gastric mucosal damage
      induced by ethanol, aspirin and stress. However, the role of reactive oxygen
      species (ROS) in the interaction between COX specific inhibitors and afferent
      sensory nerves has not been extensively studied. The aim of our present study was
      to determine the participation of ROS in pathogenesis of stress-induced gastric
      lesions in rats administered with SC-560 or rofecoxib, with or without ablation
      of the sensory afferent nerves. ROS were estimated by measuring the gastric
      mucosal tissue level of MDA and 4-HNE, the products of lipid peroxidation by ROS
      as well as the SOD activity and reduced glutathione (GSH) levels, both considered
      to be scavengers of ROS. It was demonstrated that exposure to 3.5 h of WRS
      resulted in gastric lesions, causing a significant increase of MDA and 4-HNE in
      the gastric mucosa, accompanied by a decrease of SOD activity and mucosal GSH
      level. Pretreatment with COX-1 and COX-2 inhibitors (SC-560 and rofecoxib,
      respectively) aggravated the number of gastric lesions, decreased GBF, attenuated
      GSH level without further significant changes in MDA and 4-HNE tissue levels and
      SOD activity. Furthermore, the capsaicin--nactivation of sensory nerves resulted
      in exaggeration of gastric mucosal damage induced by WRS and this was further
      augmented by rofecoxib. We conclude that oxidative stress, as reflected by an
      increase of MDA and 4-HNE tissue concentrations (an index of lipid peroxidation),
      as well as decrease of SOD activity and the fall in GSH tissue level, may play an
      important role in the mechanism of interaction between the inhibition of COX
      activity and afferent sensory nerves releasing vasoactive neuropeptides. This is
      supported by the fact that the addition of specific COX-1 or COX-2 inhibitors to
      animals with capsaicin denervation led to exacerbation of gastric lesions, and
      further fall in the antioxidizing status of gastric mucosa exposed to stress.

PMID- 22653903
TI  - Ageing influences the effect of pre-hypoxic administration of clonidine, an
      alpha2-adrenoceptor agonist, on post-hypoxic vasomotricity.
AB  - In a previous study, we showed that clonidine, an alpha2-adrenoceptor agonist,
      administered prior to hypoxia improves post-hypoxic contractility (PC) and
      endothelium-dependent dilatation (PED) in isolated young rat aortas. These
      effects were not investigated in old rats. Ageing influences vascular physiology
      and modifies the response to vasoactive drugs. Some drugs, such as simvastatin,
      improve endothelial function, a pivotal component of vascular homeostasis. This
      study intends to investigate the effect of pre-hypoxic clonidine administration
      on post-hypoxic vasomotricity in old rats with or without simvastatin. Isolated
      aortic rings from young and old rats were submitted to hypoxia/reoxygenation (20
      min/40 min). For each aorta ring from one rat, clonidine (10-5 M) was
      administered in two randomised baths and washed out before hypoxia; two other
      baths constituted the control group. In some experiments, the old rats were
      treated with simvastatin (10 mg x kg-1 x day-1) 3 days prior to hypoxia. PED and
      PC were assessed in all baths. Clonidine enhances PED in young rats (p<0.001) but
      decreases it in old rats (p=0.038). In young rats, clonidine improves PC
      (p<0.001), but this effect is not present in old rats (p=0.339). Without
      endothelium, clonidine does not influence PC in young rats (p= 0.687) but
      decreases it in old rats (p<0.001). In the simvastatin group, clonidine improves
      PED (p<0.001) but does not influence PC (p=0.203). In young rats, clonidine
      increases PED and PC, while it decreases PED and does not influence PC in old
      rats. With simvastatin, clonidine improves PED but does not influence PC.

PMID- 22653902
TI  - Nitroxide pirolin reduces oxidative stress generated by doxorubicin and docetaxel
      in blood plasma of rats bearing mammary tumor.
AB  - Combination of doxorubicin (DOX) and docetaxel (DTX) is clinically effective
      against many drug-refractory cancers, nevertheless, enhanced side effects, e.g.
      cardiotoxicity related to oxidative damage of tissue macromolecules is observed.
      Nitroxides represent an attractive class of synthetic compounds to ameliorate DOX
      DTX toxicity in non-targeted tissues due to their antioxidant and iron-oxidizing
      properties. The aim of the study was to define the ability of 3
      carbamoylpyrroline nitroxyl derivative pirolin (PL) to mitigate oxidative damage
      to blood plasma proteins and lipids induced by DOX-DTX chemotherapy in Sprague
      Dawley rats bearing DMBA-induced mammary tumor. Additionally we also evaluated:
      i) pro-oxidant and antioxidant activity of pirolin administered as a single agent
      according to different regimens and ii) differences in biomarkers of the
      oxidative stress between healthy rats and rats with DMBA-induced mammary tumors.
      The extent of oxidative stress was evaluated on the basis of its foremost
      biomarkers: thiol and carbonyl groups, lipid peroxidation products
      (hydroperoxides, TBARS), activity of antioxidant defense enzyme superoxide
      dismutase (SOD) and non-enzymatic antioxidant capacity (NEAC). We have found that
      pirolin alone displayed dual, antioxidant and pro-oxidant activity depending on
      the regimen of treatment. Daily treatment for 2 weeks increased the amount of
      thiols, and decreased the protein carbonyl groups. Three administrations of
      pirolin at 3-week intervals did not influence thiol content but increased
      hydroperoxides, TBARS and carbonyl groups. Chemotherapy employing DOX-DTX
      combination caused considerable oxidative stress in the plasma. Significant and
      dose-dependent oxidative damage to lipids and proteins with concomitant thiol
      depletion were evident in treated animals. Drugs also increased SOD activity and
      NEAC. Association of pirolin with DOX-DTX chemotherapy resulted in a partial
      amelioration of oxidative stress generated by anticancer drugs. This study
      indicates that a nitroxyl compound pirolin applied as a single agent in vivo can
      display both antioxidant and pro-oxidant properties but in conjunction with DOX
      DTX it is able to protect partially blood plasma against oxidative stress
      generated by chemotherapy. The outcome, however, seems to be highly dependent on
      the ratio between the doses of employed anticancer drugs and the nitroxide.

PMID- 22653904
TI  - Repeated blockade of 5-HT7 receptors depresses glutamatergic transmission in the
      rat frontal cortex.
AB  - The effects of the intraperitoneal administration of the 5-HT7 receptor
      antagonist SB 269970 were studied in the rat frontal cortex. In ex vivo slices
      prepared from rats receiving 14 daily doses of the drug (1.25 mg/kg) the mean
      frequency and the mean amplitude of glutamate-mediated, spontaneous excitatory
      postsynaptic currents (sEPSCs) recorded from layer II/III pyramidal neurons, were
      decreased. In contrast, single administration of SB 269970 affected neither the
      frequency nor the amplitude of sEPSCs. Treatment with SB 269970 did not affect
      membrane excitability of pyramidal cells. These data indicate that repeated, but
      not single, treatment with SB 269970 results in an attenuation of glutamatergic
      transmission in the frontal cortex, most likely due to a combination of pre- and
      postsynaptic mechanisms.

PMID- 22653905
TI  - Dimethyl sulfoxide in a 10% concentration has no effect on oxidation stress
      induced by ovalbumin-sensitization in a guinea-pig model of allergic asthma.
AB  - In allergic asthma, activated cells produce various substances including reactive
      oxygen species (ROS). As heterogenic pathophysiology of asthma results to
      different response to the therapy, testing novel interventions continues. Because
      of water-insolubility of some potentially beneficial drugs, dimethyl sulfoxide
      (DMSO) is often used as a solvent. Based on its antioxidant properties, this
      study evaluated effects of DMSO on mobilization of leukocytes into the lungs, and
      oxidation processes induced by ovalbumin (OVA)-sensitization in a guinea-pig
      model of allergic asthma. Guinea-pigs were divided into OVA-sensitized and naive
      animals. One group of OVA-sensitized animals and one group of naive animals were
      pretreated with 10% DMSO, the other two groups were given saline. After
      sacrificing animals, blood samples were taken and total antioxidant status (TAS)
      in the plasma was determined. Left lungs were saline-lavaged and differential
      leukocyte count in bronchoalveolar lavage fluid (BAL) was made. Right lung tissue
      was homogenized, TAS and products of lipid and protein oxidation were determined
      in the lung homogenate and in isolated mitochondria. OVA-sensitization increased
      total number of cells and percentages of eosinophils and neutrophils in BAL
      fluid; increased lipid and protein oxidation in the lung homogenate and
      mitochondria, and decreased TAS in the lungs and plasma compared with naive
      animals. However, no differences were observed in DMSO-instilled animals compared
      to controls. In conclusion, OVA-sensitization increased mobilization of
      leukocytes into the lungs and elevated production of ROS, accompanied by decrease
      in TAS. 10% DMSO had no effect on lipid and protein oxidation in a guinea-pig
      model of allergic asthma.

PMID- 22653906
TI  - The content of myosin heavy chains in hindlimb muscles of female and male rats.
AB  - The aim of the study was to test whether the considerable differences in the
      hindlimb muscles mass, the number and diameter of muscles fibers were connected
      with differences in the myosin heavy chain isoform content (expressed as the
      percentage of the given isoform in respect to total myosin heavy chains).
      Therefore, the content of myosin heavy chain (MHC) isoforms was studied in four
      hindlimb muscles: flexor digitorum brevis, soleus, tibialis anterior and
      gastrocnemius medialis of female and male rats by means of polyacrylamide gel
      electrophoresis supplemented with densitometric analyses. Muscles were isolated
      and homogenized prior to electrophoretic analysis. The most interesting result
      concerned considerably different composition of myosin isoforms for male and
      female subjects in the slow soleus muscles, which contained predominantly slow
      MHC isoform (MHC I). However, in the male muscle about 13% of IIa isoform (MHC
      IIa) was also detected; this isoform was not found in the majority of the studied
      female muscles (81% of muscle samples). This dimorphic difference was further
      confirmed by immunofluorescence stainining for slow and fast skeletal myosin
      isoforms and by assessment of the fiber ATPase activity. For the three remaining
      fast muscles (flexor digitorum brevis, tibialis anterior and gastrocnemius
      medialis) all four MHC isoforms were detected with the fast isoforms being
      dominant ones. However, there were not statistically significant differences
      observed between males and females, with the exception of IIx isoform, which was
      more frequent in male tibialis anterior muscle.

PMID- 22653907
TI  - Expression of ghrelin and its receptor in porcine ovarian follicles collected
      from prepubertal and estrous cycle animals.
AB  - Ghrelin, a hormone predominantly found in the stomach, was described as a factor
      that controls female reproductive function. Using real time PCR and western blot,
      we measured gene and protein expression of ghrelin and its receptor. Enzyme-like
      immunoassay (ELISA) was used to measure the concentration of acylated (Ac) and
      unacylated (UnAc) forms of ghrelin as well as levels of estradiol (E2) in
      follicular fluid. For all analyses, we compared small, medium and large ovarian
      follicles collected from ovaries of prepubertal and estrous cycling pigs. We
      demonstrated that the gene expression levels of ghrelin significantly increased
      in ovarian follicles from cycling animals, with the maximum expression in large
      follicles, without any change in prepubertal. However, the protein expression of
      ghrelin and its concentration was increased with increasing follicle size both in
      prepubertal and cycling animals and it was positively correlated with E2 levels
      in follicular fluid. In addition, both receptor growth hormone secretagogue
      receptor (GHSR) and GHSR type GHSR-1a expression were significantly higher in
      ovarian follicles from cycling animals than prepubertal. Results of this study
      suggest the possibility of local synthesis of ghrelin in the ovarian follicles
      and point to important modulatory functions for ghrelin before puberty and during
      the estrous cycle.

PMID- 22653908
TI  - Low dose pioglitazone does not affect bone formation and resorption markers or
      bone mineral density in streptozocin-induced diabetic rats.
AB  - Our study aims to investigate the effect of a low-dose pioglitazone regimen on
      bone mineral density and bone formation-resorption markers in control and
      diabetic rats. Wistar rats were divided into 4 groups: non-diabetic controls,
      control rats receiving pioglitazone (3 mg/kg), streptozocin-treated diabetic rats
      (50 mg/kg), diabetic rats treated with pioglitazone (3 mg/kg). The duration of
      the experiment was 8 weeks. Diabetes in our rats was associated with weight loss,
      increased urinary calcium excretion and reduced plasma osteocalcin levels.
      Diabetes mellitus did not affect bone mineral density. Pioglitazone
      administration had no impact on bone formation and resorption markers levels and
      did not modify bone mineral density in the four studied groups. Pioglitazone at
      the 3 mg/kg dose was not associated with significant skeletal complications in
      our experimental model.

PMID- 22653909
TI  - Bis[N,N'-diisopropylbenzamidinato(-)]silicon(II): a silicon(II) compound with
      both a bidentate and a monodentate amidinato ligand.
AB  - Well looked-after: reductive HCl elimination of the lambda(6)-silicon(IV) complex
      1 leads to the lambda(3)-silicon(II) species 2, a novel type of donor-stabilized
      silylene. Reaction of 2 with [W(CO)(6)] and with I(2) yields the lambda(5)
      silicon(II) complex 3 and the lambda(6)-silicon(IV) complex 4, respectively.

PMID- 22653910
TI  - Cell-based high-throughput screens for the discovery of chemotherapeutic agents.
AB  - With modern advances in robotics and data processing, high-throughput screening
      (HTS) is playing an increasingly growing role in the drug discovery process. The
      ultimate success of HTS depends upon the development of assays that are robust
      and reproducible in miniaturized formats, have low false-positive rates, and can
      identify drugs that offer improvements over those currently on the market. One
      example of such an assay is the ATAD5-luciferase HTS assay, which identified
      three antioxidants that could kill cancer cells without inducing mutagenesis.
      Here we discuss the ATAD5- luciferase assay and expand upon the value of HTS in
      identifying other potential cancer drugs, focusing on cell-based assays that
      involve DNA damage or repair pathways.

PMID- 22653912
TI  - High-throughput screening of a diversity collection using biodefense category A
      and B priority pathogens.
AB  - One of the objectives of the National Institutes of Allergy and Infectious
      Diseases (NIAID) Biodefense Program is to identify or develop broad-spectrum
      antimicrobials for use against bioterrorism pathogens and emerging infectious
      agents. As a part of that program, our institution has screened the 10 000
      compound MyriaScreen Diversity Collection of high-purity druglike compounds
      against three NIAID category A and one category B priority pathogens in an effort
      to identify potential compound classes for further drug development. The
      effective use of a Clinical and Laboratory Standards Institute-based high
      throughput screening (HTS) 96-well-based format allowed for the identification of
      49 compounds that had in vitro activity against all four pathogens with minimum
      inhibitory concentration values of <=16 ug/mL. Adaptation of the HTS process was
      necessary to conduct the work in higher-level containment, in this case,
      biosafety level 3. Examination of chemical scaffolds shared by some of the 49
      compounds and assessment of available chemical databases indicates that several
      may represent broad-spectrum antimicrobials whose activity is based on novel
      mechanisms of action.

PMID- 22653913
TI  - Development of a high-content high-throughput screening assay for the discovery
      of ATM signaling inhibitors.
AB  - The genome is constantly exposed to DNA damage agents, leading up to as many as 1
      million individual lesions per cell per day. Cells have developed a variety of
      DNA damage repair (DDR) mechanisms to respond to harmful effects of DNA damage.
      Failure to repair the damaged DNA causes genomic instability and, as a result,
      leads to cellular transformation. Indeed, deficiencies of DDR frequently occur in
      human cancers, thus providing a great opportunity for cancer therapy by
      developing anticancer agents that work by synthetic lethality-based mechanisms or
      enhancing the clinical efficacy of radiotherapy and existing chemotherapies.
      Ataxia-telangiectasia mutated (ATM) plays a key role in regulating the cellular
      response to DNA double-strand breaks. Ionizing radiation causes double-strand
      breaks and induces rapid ATM autophosphorylation on serine 1981 that initiates
      ATM kinase activity. Activation of ATM results in phosphorylation of many
      downstream targets that modulate numerous damage-response pathways, most notably
      cell-cycle checkpoints. We describe here the development and validation of a high
      throughput imaging assay measuring levels of phospho-ATM Ser1981 in HT29 cells
      after exposure to ionizing radiation. We also examined activation of downstream
      ATM effectors and checked specificity of the endpoint using known inhibitors of
      DNA repair pathways.

PMID- 22653914
TI  - Rugulactone and its analogues exert antibacterial effects through multiple
      mechanisms including inhibition of thiamine biosynthesis.
AB  - Rugulactone is a dihydro-alpha-pyrone isolated from the plant Cryptocarya
      rugulosa in 2009. It has been reported to display IkB kinase (IKK) inhibitory
      activity, as well as antibiotic activity in several strains of pathogenic
      bacteria. However, its biological targets and mode of action in bacteria have not
      yet been explored. Here we present enantioselective syntheses of rugulactone and
      of some corresponding activity-based protein profiling (ABPP) probes. We found
      that the ABPP probes in this study are more potent than rugulactone against
      Staphyloccocus aureus NCTC 8325, S. aureus Mu50, Listeria welshimeri SLCC 5334
      and Listeria monocytogenes EGD-e, and that molecules of this class probably exert
      their antibacterial effect through a combination of targets. These targets
      include covalent inhibition of 4-amino-5-hydroxymethyl-2-methylpyrimidine
      phosphate (HMPP) kinase (ThiD), which is an essential component of the thiamine
      biosynthesis pathway in bacteria. This represents the first example of a small
      molecule inhibitor of ThiD.

PMID- 22653915
TI  - Postprandial glycaemia in cats fed a moderate carbohydrate meal persists for a
      median of 12 hours--female cats have higher peak glucose concentrations.
AB  - The postprandial increase in glucose concentration is typically not considered in
      selecting diets to manage diabetic and pre-diabetic cats. This study describes
      increases in glucose and insulin concentrations in 24 clinically healthy,
      neutered adult cats following one meal (59 kcal/kg) of a moderate carbohydrate
      diet (25% of energy). Median time to return to baseline after feeding for glucose
      was 12.2 h (1.8->=24 h) and for insulin was 12.3 h (1.5->=24 h). Time to return
      to baseline for glucose was not different between male (10.2 h) and female (17.2
      h) cats. There was evidence female cats had a longer return to baseline for
      insulin (18.9 h versus 9.8 h) and females had higher (0.9 mmol/l difference) peak
      glucose than males. This demonstrates that the duration of postprandial glycaemia
      in cats is markedly longer than in dogs and humans, and should be considered when
      managing diabetic and pre-diabetic cats.

PMID- 22653917
TI  - The use and productivity of past tense morphology in specific language
      impairment: an examination of Danish.
AB  - PURPOSE: The authors' primary goal was to investigate the potential of past tense
      inflection as a clinical marker of Danish specific language impairment (SLI).
      They also wished to test the predictions of the extended optional infinitive
      (EOI) account and processing based accounts of SLI on Danish. METHOD: Using
      sentence completion and sentence repetition tasks, the authors investigated the
      use of past tense by 3 groups (  n = 11 in each group): (a) children with SLI
      whose ages ranged from 5;2 (years;months) to 7;11; (b) children with typical
      language development matched on chronological age; and (c) children with typical
      language development matched on vocabulary. RESULTS: Participants with SLI were
      less likely to produce past tense than were both typically developing control
      groups. In particular, only the children with SLI had difficulties with
      accurately producing past tense verbs during the sentence repetition task. Past
      tense accuracy was associated with children's productive vocabulary levels and
      proficiency with a nonword repetition task. CONCLUSION: Past tense use is
      potentially a clinical marker of Danish SLI, but more research is needed to
      confirm this. Results provided mixed support for competing accounts of SLI.

PMID- 22653916
TI  - Indirect estimates of jaw muscle tension in children with suspected hypertonia,
      children with suspected hypotonia, and matched controls.
AB  - PURPOSE: In this study, the authors compared indirect estimates of jaw-muscle
      tension in children with suspected muscle-tone abnormalities with age- and gender
      matched controls. METHOD: Jaw movement and muscle activation were measured in
      children (ages 3 years, 11 months, to 10 years) with suspected muscle-tone
      abnormalities (Down syndrome or spastic cerebral palsy; n = 10) and controls (n =
      11). Two measures were used to infer jaw tension: a kinematic index of mass
      normalized stiffness and electromechanical delay (EMD). The kinematic index used
      video-based kinematics to obtain the slope of the peak velocity-displacement
      relationship. The EMD was derived from the interval between the onset of
      suprahyoid muscle activity and the onset of jaw depression. RESULTS: Neither
      measure differentiated the groups. The kinematic index revealed differences
      between stressed and unstressed syllables in 3-syllable productions by the
      participants with cerebral palsy and controls, but not in 2-syllable productions
      by the participants with Down syndrome and controls. CONCLUSION: This preliminary
      investigation included the novel application of 2 measures to infer the jaw
      muscle tension of children with suspected tone abnormalities. Although the
      results do not support the hypothesis that suspected muscle-tone abnormalities
      affect jaw movement sufficiently to influence speech production, considerations
      for interpreting the findings include methodological limitations and possible
      compensatory muscle coactivation.

PMID- 22653918
TI  - Audiovisual speech perception in children with developmental language disorder in
      degraded listening conditions.
AB  - PURPOSE: The effect of the signal-to-noise ratio (SNR) on the perception of
      audiovisual speech in children with and without developmental language disorder
      (DLD) was investigated by varying the noise level and the sound intensity of
      acoustic speech. The main hypotheses were that the McGurk effect (in which
      incongruent visual speech alters the auditory speech percept) would be weaker for
      children with DLD than for controls and that it would get stronger with
      decreasing SNR in both groups. METHOD: The participants were 8-year-old children
      with DLD and a sample of children with normal language development. In the McGurk
      stimuli, the consonant uttered by the voice differed from that articulated by the
      face. Three sound intensities (24, 36, and 48 dB) and noise levels (-12, 0, and
      +6 dB) were used. Perception of unisensory visual speech was also measured.
      RESULTS: The children with DLD experienced a weak McGurk effect, that is, a weak
      influence of visual speech on audiovisual speech perception, which remained
      rather constant across SNR levels. The children with DLD were inaccurate at
      lipreading. CONCLUSIONS: Children with DLD have problems in perceiving spoken
      consonants presented audiovisually and visually. The weaker McGurk effect could
      be accounted for by the poorer lipreading ability of children with DLD.

PMID- 22653919
TI  - Additive effects of lengthening on the utterance-final word in child-directed
      speech.
AB  - PURPOSE: The authors investigated lengthening effects in child-directed speech
      (CDS) across the sentence, testing the additive effects on duration of Word
      Position, Register, Focus, and Sentence Mode (statement/question). METHOD: Five
      theater students produced 6 sentences containing 5 monosyllabic words in a
      simulated dialogue, varying in Register, Focus, and Sentence Mode. The authors
      segmented a total of 1,800 sentences using forced-alignment tools, and they
      analyzed the duration of each word. RESULTS: The results show significant effects
      of Register, Word Position, and their interactions. The simple effect of Register
      was significant in all 5 word positions, indicating a global elongation effect in
      CDS. Interestingly, there was no proportional increase of the final word in CDS.
      In addition, the 3-way interactions Register * Word Position * Focus and Register
      * Word Position * Sentence Mode were significant, which converge to the
      conclusion that the utterance-final word in CDS is additively elongated when it
      is focused and in a statement. CONCLUSION: Elongation in CDS is a global effect,
      but the additive effects of duration demonstrated in the authors' data suggest
      that the effect of enhanced utterance-final lengthening in CDS in naturalistic
      samples may be a by-product of discourse characteristics of CDS.

PMID- 22653921
TI  - Significant association of the dupA gene of Helicobacter pylori with duodenal
      ulcer development in a South-east Indian population.
AB  - A novel virulence factor, duodenal ulcer-promoting gene A (dupA), in Helicobacter
      pylori has been found to be associated with disease in certain populations but
      not in others. This study analysed a South-east Indian population as part of the
      debate about the relevance of dupA for the prediction of clinical outcomes. A
      total of 140 H. pylori strains isolated from duodenal ulcer (DU) (n = 83) and non
      ulcer dyspepsia (NUD) patients (n = 57) were screened by PCR and dot-blot
      hybridization to determine the presence of the ORFs jhp0917 and jhp0918. Part of
      jhp0917-jhp0918 was sequenced to search for the C/T insertion that characterizes
      dupA and the levels of dupA transcripts were also assessed. The PCR and dot-blot
      results indicated the presence of jhp0917 and jhp0918 in 37.3 % (31/83) and 12.2
      % (7/57) of H. pylori strains isolated from DU and NUD patients, respectively.
      Sequencing analysis showed insertion of a C at nt 1386 in the 3' region of
      jhp0917, forming the dupA gene in 35 strains. RT-PCR analysis detected the dupA
      transcript in 28 of these 35 strains. The expression level of the dupA transcript
      varied from strain to strain, as shown by real-time PCR. The results demonstrated
      that analysis based on PCR only for dupA may produce an erroneous interpretation.
      The prevalence of dupA was significantly greater among strains isolated from
      patients with DU than from patients with NUD in this population (P = 0.001, odds
      ratio = 4.26, confidence interval = 1.60-11.74). Based on these findings, dupA
      can be considered a biomarker for DU patients in India. The reported
      discrepancies for this putative virulence marker in different populations may be
      due to the genome plasticity of H. pylori.

PMID- 22653922
TI  - Echinocandin resistance due to simultaneous FKS mutation and increased cell wall
      chitin in a Candida albicans bloodstream isolate following brief exposure to
      caspofungin.
AB  - Echinocandins are first-line agents for treating severe invasive candidiasis.
      Glucan synthase gene (FKS1) mutations lead to echinocandin resistance but the
      role of enhanced chitin expression is not well recognized in clinical isolates.
      We report a case of bloodstream Candida albicans infection with both Fks1 hotspot
      mutation and elevated cell wall chitin.

PMID- 22653920
TI  - Proteomic profiling of the planarian Schmidtea mediterranea and its mucous
      reveals similarities with human secretions and those predicted for parasitic
      flatworms.
AB  - The freshwater planarian Schmidtea mediterranea has been used in research for
      over 100 years, and is an emerging stem cell model because of its capability of
      regenerating large portions of missing body parts. Exteriorly, planarians are
      covered in mucous secretions of unknown composition, implicated in locomotion,
      predation, innate immunity, and substrate adhesion. Although the planarian genome
      has been sequenced, it remains mostly unannotated, challenging both genomic and
      proteomic analyses. The goal of the current study was to annotate the proteome of
      the whole planarian and its mucous fraction. The S. mediterranea proteome was
      analyzed via mass spectrometry by using multidimensional protein identification
      technology with whole-worm tryptic digests. By using a proteogenomics approach,
      MS data were searched against an in silico translated planarian transcript
      database, and by using the Swiss-Prot BLAST algorithm to identify proteins
      similar to planarian queries. A total of 1604 proteins were identified. The
      mucous subproteome was defined through analysis of a mucous trail fraction and an
      extract obtained by treating whole worms with the mucolytic agent N
      acetylcysteine. Gene Ontology analysis confirmed that the mucous fractions were
      enriched with secreted proteins. The S. mediterranea proteome is highly similar
      to that predicted for the trematode Schistosoma mansoni associated with
      intestinal schistosomiasis, with the mucous subproteome particularly highly
      conserved. Remarkably, orthologs of 119 planarian mucous proteins are present in
      human mucosal secretions and tear fluid. We suggest planarians have potential to
      be a model system for the characterization of mucous protein function and
      relevant to parasitic flatworm infections and diseases underlined by mucous
      aberrancies, such as cystic fibrosis, asthma, and other lung diseases.

PMID- 22653924
TI  - A membership benefit we all can enjoy: highlights of the scientific program of
      the 2012 ADA Annual Session.

PMID- 22653925
TI  - A new model for caries classification and management: the FDI World Dental
      Federation caries matrix.

PMID- 22653923
TI  - Allosteric conversation in the androgen receptor ligand-binding domain surfaces.
AB  - Androgen receptor (AR) is a major therapeutic target that plays pivotal roles in
      prostate cancer (PCa) and androgen insensitivity syndromes. We previously
      proposed that compounds recruited to ligand-binding domain (LBD) surfaces could
      regulate AR activity in hormone-refractory PCa and discovered several surface
      modulators of AR function. Surprisingly, the most effective compounds bound
      preferentially to a surface of unknown function [binding function 3 (BF-3)]
      instead of the coactivator-binding site [activation function 2 (AF-2)]. Different
      BF-3 mutations have been identified in PCa or androgen insensitivity syndrome
      patients, and they can strongly affect AR activity. Further, comparison of AR x
      ray structures with and without bound ligands at BF-3 and AF-2 showed structural
      coupling between both pockets. Here, we combine experimental evidence and
      molecular dynamic simulations to investigate whether BF-3 mutations affect AR LBD
      function and dynamics possibly via allosteric conversation between surface sites.
      Our data indicate that AF-2 conformation is indeed closely coupled to BF-3 and
      provide mechanistic proof of their structural interconnection. BF-3 mutations may
      function as allosteric elicitors, probably shifting the AR LBD conformational
      ensemble toward conformations that alter AF-2 propensity to reorganize into
      subpockets that accommodate N-terminal domain and coactivator peptides. The
      induced conformation may result in either increased or decreased AR activity.
      Activating BF-3 mutations also favor the formation of another pocket (BF-4) in
      the vicinity of AF-2 and BF-3, which we also previously identified as a hot spot
      for a small compound. We discuss the possibility that BF-3 may be a protein
      docking site that binds to the N-terminal domain and corepressors. AR surface
      sites are attractive pharmacological targets to develop allosteric modulators
      that might be alternative lead compounds for drug design.

PMID- 22653926
TI  - Prosthetic joint infections.

PMID- 22653928
TI  - Cow milk and caries.

PMID- 22653930
TI  - Infants and fluoride.

PMID- 22653932
TI  - NCCL or AAE?

PMID- 22653934
TI  - A question of coverage.

PMID- 22653936
TI  - Length of tooth survival in older adults with complex medical, functional and
      dental backgrounds.
AB  - BACKGROUND: Tooth loss can be considered a failure of current oral health care
      strategies. Knowing how soon this failure will occur can help clinicians enhance
      preventive strategies for preventing tooth loss and minimizing its impact. The
      authors conducted a study to detail tooth survival patterns in an older cohort.
      METHODS: The authors conducted a retrospective longitudinal study of 491
      participants aged 43 to 102 years. They treated the participants' dental
      conditions before they entered the study. They also collected participants'
      sociodemographic, medical, functional, cognitive and dental data when they first
      arrived at the clinic. The authors used Fisher exact tests, chi(2) tests and
      analysis of variance to examine the association between baseline characteristics
      and tooth survival. They generated Kaplan-Meier estimates and used Cox
      proportional hazards regression models to detail tooth survival and associated
      risk factors. RESULTS: The authors found that tooth survival patterns differed
      among participants who had different numbers of carious teeth or retained roots
      (carious or broken teeth that were missing most of their coronal structures) when
      they first arrived at the clinic (P < .001) and between participants who wore
      removable prostheses and those who did not (P = .02). Participants' tooth loss at
      different times differed by sex, number of medications being taken and number of
      carious teeth or retained roots. The authors found that after they adjusted for
      other factors, tooth survival was associated with the number of carious teeth or
      retained roots (P = .01), as well as the interaction between the number of
      carious teeth or retained roots and use of prostheses (P = .02). CONCLUSIONS:
      Caries and the use of removable prostheses synergistically compromised tooth
      survival in older patients. Patients who wore prostheses and had multiple active
      carious teeth or retained roots at arrival had the highest risk of losing teeth
      soon after their existing conditions were treated. CLINICAL IMPLICATIONS: These
      findings highlight the need for preventing tooth loss in older adults who wear
      removable prostheses and have poor oral health. Knowing the groups at the highest
      risk of experiencing tooth loss soon after dental treatment is received can help
      dentists better target and design preventive strategies.

PMID- 22653937
TI  - The effects of home-use and in-office bleaching treatments on calcium and
      phosphorus concentrations in tooth enamel: an in vivo study.
AB  - BACKGROUND: Because the effects of dental bleaching on enamel needs to be
      clarified in vivo, the authors conducted a study to determine calcium and
      phosphorus concentrations in enamel after the application of different bleaching
      treatments. METHODS: The authors applied four agents (10 percent and 20 percent
      carbamide peroxide [both recommended for home use], 38 percent and 35 percent
      hydrogen peroxide [both applied in the dental office]) to the enamel of 80
      participants, who were divided into four groups of 20. The authors collected
      enamel microbiopsy specimens from incisors before (baseline), during (seven, 14
      and 21 days) and after (seven and 14 days) the bleaching treatments. They
      analyzed calcium and phosphorus concentrations by using a spectrophotometer.
      RESULTS: The authors analyzed data by using the Friedman test and the Kruskal
      Wallis test, followed by the Dunn test (alpha= .05). There were no statistical
      differences between the evaluation results, regardless of which bleaching gel was
      used, for determining the concentration of either calcium or phosphorus.
      CONCLUSIONS: Home-use and in-office bleaching gels did not alter the
      concentrations of calcium and phosphorus concentrations on the enamel surface in
      vivo. CLINICAL IMPLICATIONS: In vivo, different dental bleaching techniques did
      not alter the inorganic composition of enamel.

PMID- 22653938
TI  - Dietary and nutritional needs of patients after therapy for head and neck cancer.
AB  - BACKGROUND: The number of cancer survivors in the general population is
      increasing. Oral and dental status affects patients' quality of life and oral
      function, which, in turn, may affect nutritional intake and general health. The
      authors review the importance of oral health and the role of the oral health care
      provider in supporting dietary intake and providing nutritional guidance.
      METHODS: The authors provide a brief review of oral complications of therapy and
      nutritional guidelines for patients with head and neck cancer. RESULTS: Oral
      adverse effects of head and neck cancer treatment include salivary gland
      dysfunction, taste change, orofacial pain and mucosal sensitivity, oral
      infection, tissue defects and necrosis, trismus and fibrosis, progressive dental
      and periodontal disease, and problems with prosthesis function. CONCLUSIONS:
      Managing oral adverse effects of treatment may have an impact on dietary and
      nutritional intake, as well as on quality of life. Dietary modifications may be
      needed because of the patient's oral function and may include modification of
      food texture and flavor, as well as the use of dietary supplements. CLINICAL
      IMPLICATIONS: As part of the patient's health care team, dental care
      professionals should be aware of the oral adverse effects of cancer therapy, as
      well as their role in recognizing and treating the resulting oral conditions. In
      addition, they should provide guidance to patients to support their oral dietary
      and nutritional intake.

PMID- 22653939
TI  - Repair or replacement of defective restorations by dentists in The Dental
      Practice-Based Research Network.
AB  - BACKGROUND: The authors aimed to determine whether dentists in practices
      belonging to The Dental Practice-Based Research Network (DPBRN) were more likely
      to repair or to replace a restoration that they diagnosed as defective; to
      quantify dentists' specific reasons for repairing or replacing restorations; and
      to test the hypothesis that certain dentist-, patient- and restoration-related
      variables are associated with the decision between repairing and replacing
      restorations. METHODS: This cross-sectional study had a consecutive patient and
      restoration recruitment design. Practitioner-investigators (P-Is) recorded data
      for consecutively seen restorations in permanent teeth that needed repair or
      replacement. The DPBRN is a consortium of dental practitioners and dental
      organizations in the United States and Scandinavia. The collected data included
      the primary reason for repair or replacement, tooth surface or surfaces involved,
      restorative materials used and patients' demographic information. RESULTS: P-Is
      collected data regarding 9,484 restorations from 7,502 patients in 197 practices.
      Seventy-five percent (7,073) of restorations were replaced and 25 percent (2,411)
      repaired. Secondary caries was the main reason (43 percent, n = 4,124) for
      treatment. Factors associated with a greater likelihood of repairing versus
      replacing restorations (P < .05) included having graduated from dental school
      more recently, practicing in a large group practice, being the dentist who placed
      the original restoration, patient's being of an older age, the original
      restorative material's being something other than amalgam, restoration of a molar
      and the original restoration's involving fewer tooth surfaces. CONCLUSIONS: DPBRN
      dentists were more likely to replace than to repair restorations. Secondary
      caries was the most common reason for repairing or replacing restorations.
      Certain dentist-, patient- and restoration-related variables were associated with
      the repair-or-replace decision. CLINICAL IMPLICATIONS: The selection of minimally
      invasive treatment for an existing restoration is critical, as it may affect the
      longevity of the tooth.

PMID- 22653942
TI  - Assessing production characteristics, influential factors and administrative
      policies in a multicenter dental organization.
AB  - BACKGROUND: In multicenter service organizations, managers often make centralized
      decisions without considering the effects of differing production characteristics
      and influential factors on each center. METHODS: In this study, the author
      examines differences in production characteristics and factors that influence
      production, as well as their likely effect on policy formulation, in a large, six
      center dental group in the Chicago area. RESULTS: The results of the study show
      that the six centers (in two groups) exhibited two distinct production patterns,
      with three having logarithmic distributions and three having normal
      distributions. Production differences between the groups likely resulted from
      differences in managed care, staffing and dental procedures performed.
      CONCLUSIONS: Instead of being monolithic, the organization exhibited two types of
      centers, each with its own production characteristics and factors that influenced
      production. PRACTICE IMPLICATIONS: The study results suggest that large service
      corporations and }partnerships would benefit from conducting analyses of
      production characteristics and factors that influence production before making
      policy decisions that affect the entire organization.

PMID- 22653941
TI  - Oxalates may not be effective in treating dentin hypersensitivity.

PMID- 22653940
TI  - The effect of training on the use of tobacco-use cessation guidelines in dental
      settings.
AB  - BACKGROUND: An increase in the number of dentists conducting tobacco-use
      cessation treatment is needed. The authors assessed the effects of high-intensity
      training (HIT) or low-intensity training (LIT) and reimbursement on general
      dentists' tobacco-use-related attitudes and treatment behaviors. METHODS: The
      authors randomly selected 265 dentists in three states and assigned them to one
      of five groups: HIT workshop groups with and without tobacco-use cessation
      counseling reimbursement, LIT mailed self-study groups with and without
      reimbursement or a control group. Outcomes at follow-up were dentists' self
      reported tobacco-use-related attitudes and behaviors and patients' reports of
      dentists' behaviors. RESULTS: Significantly more dentists in the intervention
      groups reported having positive attitudes and behaviors at follow-up than did
      dentists in the control group. Dentists in the HIT groups, however, reported
      assessing patients' willingness to quit and assisting them with the quitting
      process significantly more often than did dentists in the LIT groups.
      Significantly more patients of dentists in the intervention groups who used
      tobacco reported receiving advice and assistance from their dentists than did
      patients of dentists in the control group. Adding reimbursement to HIT or LIT
      conditions did not provide additional intervention effect. CONCLUSION: Dentists
      trained by means of a workshop or self-study program used components of a
      recommended guideline more frequently and felt more positive toward tobacco-use
      cessation counseling than did dentists in the control group. CLINICAL
      IMPLICATIONS: Although the workshop training was more successful than the self
      study training, the latter's reach among dentists could have a more significant
      public health impact. The effect of reimbursement needs further study.

PMID- 22653943
TI  - The team-building myth.

PMID- 22653944
TI  - Nonsyndromic multiple hyperdontia in a series of 13 patients: epidemiologic and
      clinical considerations.
AB  - BACKGROUND: The authors conducted a retrospective-casuistic study to determine
      the prevalence of nonsyndromic multiple hyperdontia in a sample of the population
      of Madrid, as well as possible complications associated with the presence of such
      supernumerary teeth. METHODS: The study included a data assessment of all
      patients seeking dental care at a hospital's department of oral surgery across
      four years. The authors studied data from patients who had nonsyndromic multiple
      hyperdontia. We used univariate and bivariate analysis to make comparisions
      between variables. RESULTS: The authors identified nonsyndromic multiple
      hyperdontia in the records of 13 patients (0.1 percent) of the total population
      studied. These patients had 55 supernumerary teeth. Premolars were the most
      frequently seen type of supernumerary tooth and constituted 45.5 percent of the
      sample. CONCLUSIONS: Nonsyndromic multiple hyperdontia usually is diagnosed as a
      coincidental radiographic finding in the course of routine examination rather
      than as the result of an associated disease. However, the authors found a higher
      percentage of comorbidity than they initially expected; mechanical or obstructive
      pathology was associated with 20.0 percent of the supernumerary teeth and
      enlargement of the follicular sac of more than 3 millimeters was present in 23.6
      percent of the sample. CLINICAL IMPLICATIONS: The early diagnosis and follow-up
      of patients with multiple supernumerary teeth should help clinicians prevent the
      diseases associated with this kind of hyperodontia.

PMID- 22653945
TI  - Cutaneous and oral mucosal lesions in a cardiac transplant recipient.
AB  - BACKGROUND: Solid organ transplantation no longer is considered a rare procedure.
      After undergoing transplants, patients will require both routine and emergent
      oral health care, and it can be provided safely in private dental offices.
      Transplant recipients are immunosuppressed, and for this reason clinicians should
      be alert for oral abnormalities in such patients. CASE DESCRIPTION: A 53-year-old
      man with a history of cardiac transplant and multiple medical comorbidities had
      unusual mucosal plaques, oral discomfort and skin lesions. As a result of his
      compromised immune system, the clinical presentation of his condition-which
      proved to be herpes zoster (HZ) virus, also called "shingles"-was atypical,
      resulting in a delay of the definitive diagnosis. CONCLUSIONS: and CLINICAL
      IMPLICATIONS: HZ is a serious infection in the immunocompromised population.
      Timely diagnosis and treatment of this condition is necessary to prevent
      treatment delay and medication errors.

PMID- 22653946
TI  - Periplasmic proteins encoded by VCA0261-0260 and VC2216 genes together with copA
      and cueR products are required for copper tolerance but not for virulence in
      Vibrio cholerae.
AB  - The bacterial pathogen Vibrio cholerae requires colonizination of the human small
      intestine to cause cholera. The anaerobic and slightly acidic conditions
      predominating there enhance toxicity of low copper concentrations and create a
      selective environment for bacteria with evolved detoxifying mechanisms. We
      reported previously that the VCA0260, VCA0261 and VC2216 gene products were
      synthesized only in V. cholerae grown in microaerobiosis or anaerobiosis. Here we
      show that ORFs VCA0261 and VCA0260 are actually combined into a single gene
      encoding a 18.7 kDa protein. Bioinformatic analyses linked this protein and the
      VC2216 gene product to copper tolerance. Following the approach of predict-mutate
      and test, we describe for the first time, to our knowledge, the copper tolerance
      systems operating in V. cholerae. Copper susceptibility analyses of mutants in
      VCA0261-0260, VC2216 or in the putative copper-tolerance-related VC2215 (copA
      ATPase) and VC0974 (cueR), under aerobic and anaerobic growth, revealed that CopA
      represents the main tolerance system under both conditions. The VC2216-encoded
      periplasmic protein contributes to resistance only under anaerobiosis in a CopA
      functional background. The locus tag VCA0261-0260 encodes a copper-inducible,
      CueR-dependent, periplasmic protein, which mediates tolerance in aerobiosis, but
      under anaerobiosis its role is only evident in CopA knock-out mutants. None of
      the genes involved in copper homeostasis were required for V. cholerae virulence
      or colonization in the mouse model. We conclude that copper tolerance in V.
      cholerae, which lacks orthologues of the periplasmic copper tolerance proteins
      CueO, CusCFBA and CueP, involves CopA and CueR proteins along with the
      periplasmic Cot (VCA0261-0260) and CopG (VC2216) V. cholerae homologues.

PMID- 22653947
TI  - IncP-1beta plasmids of Comamonas sp. and Delftia sp. strains isolated from a
      wastewater treatment plant mediate resistance to and decolorization of the
      triphenylmethane dye crystal violet.
AB  - The application of toxic triphenylmethane dyes such as crystal violet (CV) in
      various industrial processes leads to large amounts of dye-contaminated sludges
      that need to be detoxified. Specific bacteria residing in wastewater treatment
      plants (WWTPs) are able to degrade triphenylmethane dyes. The objective of this
      work was to gain insights into the genetic background of bacterial strains
      capable of CV degradation. Three bacterial strains isolated from a municipal WWTP
      harboured IncP-1beta plasmids mediating resistance to and decolorization of CV.
      These isolates were assigned to the genera Comamonas and Delftia. The CV
      resistance plasmid pKV29 from Delftia sp. KV29 was completely sequenced. In
      addition, nucleotide sequences of the accessory regions involved in conferring CV
      resistance were determined for plasmids pKV11 and pKV36 from the other two
      isolates. Plasmid pKV29 contains typical IncP-1beta backbone modules that are
      highly similar to those of previously sequenced IncP-1beta plasmids that confer
      antibiotic resistance, degradative capabilities or mercury resistance. The
      accessory regions located between the conjugative transfer (tra) and mating pair
      formation modules (trb) of all three plasmids analysed share common modules and
      include a triphenylmethane reductase gene, tmr, that is responsible for
      decolorization of CV. Moreover, these accessory regions encode other enzymes that
      are dispensable for CV degradation and hence are involved in so-far-unknown
      metabolic pathways. Analysis of plasmid-mediated degradation of CV in Escherichia
      coli by ultra-high-performance liquid chromatography-electrospray ionization
      quadrupole-time-of-flight MS revealed that leuco crystal violet was the first
      degradation product. Michler's ketone and 4-dimethylaminobenzaldehyde appeared as
      secondary degradation metabolites. Enzymes encoded in the E. coli chromosome seem
      to be responsible for cleavage of leuco crystal violet. Plasmid-mediated
      degradation of triphenylmethane dyes such as CV is an option for the
      biotechnological treatment of sludges contaminated with these dyes.

PMID- 22653948
TI  - Global transcriptional analysis of the stringent response in Enterococcus
      faecalis.
AB  - In Enterococcus faecalis, production of guanosine tetraphosphate/guanosine
      pentaphosphate [(p)ppGpp], the effector molecule of the stringent response, is
      controlled by the bifunctional synthetase/hydrolase RelA and the monofunctional
      synthetase RelQ. Previously, the (p)ppGpp profiles of strains lacking relA, relQ
      or both genes indicated that RelA is the primary enzyme responsible for (p)ppGpp
      synthesis under stress conditions, while the contributions of RelQ to the
      stringent response and cell homeostasis remained elusive. Here, survival within
      the mouse-derived macrophage cell line J774A.1 and killing of Galleria mellonella
      supported initial evidence that virulence was attenuated in the (p)ppGpp(0)
      DeltarelADeltarelQ strain but not in the DeltarelA or DeltarelQ strains. We
      performed, for the first time to our knowledge, global transcriptome analysis in
      a documented (p)ppGpp(0) Gram-positive bacterium and provided the first insights
      into the role of a Gram-positive monofunctional (p)ppGpp synthetase in
      transcriptional regulation. Transcription profiling after mupirocin treatment
      confirmed that RelA is the major enzyme responsible for the (p)ppGpp-mediated
      transcriptional repression of genes associated with macromolecular biosynthesis,
      but also revealed that RelQ is required for full and timely stringent response
      induction. The delayed transcriptional response of DeltarelQ could not be
      correlated with reduced or slower production of (p)ppGpp, in part because RelA
      dependent (p)ppGpp accumulation occurred very rapidly. Comparisons of the
      transcriptional responses of DeltarelA or DeltarelADeltarelQ strains with the
      parent strain under starvation conditions revealed upregulation of operons
      involved in energy metabolism in the (p)ppGpp(0) strain. Thus, while DeltarelA
      and DeltarelADeltarelQ cannot use (p)ppGpp to sense and respond to stresses,
      fitness of DeltarelADeltarelQ may be further impaired due to an unbalanced
      metabolism.

PMID- 22653949
TI  - FCA: forget chemoimmunotherapy with alemtuzumab?

PMID- 22653950
TI  - Novel treatment for congenital FXIII deficiency.

PMID- 22653951
TI  - CD20 antibodies: type II to tango?

PMID- 22653952
TI  - From famine to feast: sending out the clones.

PMID- 22653953
TI  - Do not super-excess me!

PMID- 22653954
TI  - Monocytes in HIT: an evolving story.

PMID- 22653955
TI  - SNPs and GVHD prediction: where to next?

PMID- 22653956
TI  - Monoclonal antibodies against macrophage colony-stimulating factor diminish the
      number of circulating intermediate and nonclassical
      (CD14(++)CD16(+)/CD14(+)CD16(++)) monocytes in rheumatoid arthritis patient.

PMID- 22653957
TI  - Programmed vesicle transfer of green fluorescent protein from a stably transduced
      cell line to primary hematopoietic cells.

PMID- 22653958
TI  - Absence of BRAF-V600E in the human cell lines BONNA-12, ESKOL, HAIR-M, and HC-1
      questions their origin from hairy cell leukemia.

PMID- 22653959
TI  - Studying c-Myc serine 62 phosphorylation in leukemia cells: concern over antibody
      cross-reactivity.

PMID- 22653960
TI  - Does the NO/sGC/cGMP/PKG pathway play a stimulatory role in platelets?

PMID- 22653961
TI  - Extra-platelet NO and NO(+)-containing drugs are potent inhibitors of platelet
      aggregation in humans by cGMP-dependent and cGMP-independent mechanisms.

PMID- 22653962
TI  - Forward surgery and combat hospitals: the origins of the MASH.
AB  - The U.S. Army adopted forward surgical hospitals (SHs) during World War I on the
      advice of the British and French armies. The purposes were not just to save
      lives, but to benefit the military by returning more patients to duty and
      reducing the size of the hospital system through fewer infections and shorter
      hospital stays. The Army examined the utility of the units at the end of the war
      and retained them for any future conflicts, but opposition also survived. The
      question was the utility for the Army: was it worth making a substantial
      investment, and reducing care for other wounded soldiers, for the most grievously
      wounded, perhaps 1 percent of the total? Devising an effective way to organize
      forward SHs was a problem in the interwar years and early in World War II (WWII).
      But from the late 1930s, the Army never reexamined whether it should provide
      forward surgery, only how to do so, including pushing surgeons even further
      forward on the battlefield. At the end of WWII, the Mobile Army Surgical Hospital
      (MASH) was created to perform the mission, although the MASH was only the latest
      format. 

PMID- 22653963
TI  - Effect of a 60-day oral gavage of a crude alkaloid extract from Chromolaena
      odorata leaves on hormonal and spermatogenic indices of male rats.
AB  - The present study was aimed at investigating the effects of the crude  alkaloids
      isolated from Chromolaena odorata leaves on the hormonal  and spermatogenic
      indices of male rats. The alkaloids obtained from C  odorata leaves using
      standard methods were administered to male rats for  60 days at the doses of 250,
      500, and 1000 mg/kg body weight. Thin-layer  chromatographic analysis of the
      alkaloid mixture produced 8 spots, 3 of which  were alkaloids with R(f) values of
      0.41, 0.49, and 0.55 as confirmed  by the formation of orange color and creamy
      precipitates with both Dragendorff  and Mayer reagents, respectively. The
      alkaloids were represented in the  extract by a yield of 20.28 g, corresponding
      to a percentage yield of 90.05%  of the total extract of 22.52 g. The final body
      weights of both the control  and alkaloid-treated animals increased significantly
      (P < .05)  compared with their respective body weights before treatment. The
      alkaloids  significantly decreased (P < .05) the testes-body weight  ratio; the
      concentrations of testicular total protein, glycogen, sialic acid,  and
      cholesterol; and the activities of gamma-glutamyl transferase, acid  phosphatase,
      and alkaline phosphatase. The serum luteinizing hormone and  follicle-stimulating
      hormone levels, as well as testicular and serum  testosterone levels, also
      decreased significantly (P < .05). There  were decreases in the sperm count,
      motility, and density, as well as  morphological changes in the sperm cells. The
      pH and whitish-gray color of the  semen were not significantly affected. All of
      the doses of the alkaloids  increased the total mean number of sperm cell
      abnormalities, with the  secondary type predominating over the primary sperm cell
      abnormality. The  alterations in the levels of the hormones and secretory and
      synthetic  constituents of the testes and the spermatotoxic effects by the
      alkaloids from  C odorata leaves may be due to nonavailability or deprivation of 
      testosterone to the target organ. This lack of testosterone may have 
      consequential effects on the reproductive process of the male rat.

PMID- 22653964
TI  - NADPH oxidase activation: a mechanism of erectile dysfunction in a rat model of
      sleep apnea.
AB  - Erectile dysfunction (ED) is a frequent occurrence in male patients with 
      obstructive sleep apnea syndrome (OSAS). Long-term intermittent hypoxia  (LTIH),
      one of the hallmarks of OSAS, could mediate ED. The objective of this  study was
      to test the hypothesis that increased nicotinamide adenine  dinucleotide
      phosphate (NADPH) oxidase activity contributes to ED in rat  responses to LTIH.
      Healthy male Sprague-Dawley rats were randomly distributed  into 4 groups: a LTIH
      group, an apocynin (a selective NADPH oxidase  inhibitor)-treated LTIH group, a
      sham LTIH group, and an apocynin-treated sham  group. Erectile function was
      examined by measuring the mean arterial blood  pressure (MAP) and intracavernosal
      pressure (ICP) on electrical stimulation of  the cavernous nerve. Real-time
      quantitative polymerase chain reaction and  Western blot were used to examine
      mRNA and protein expression of NADPH oxidase  subunit in corpus cavernosa (CC).
      The level of malondialdehyde and superoxide  dismutase were detected by
      colorimetry. Nitric oxide synthase (NOS) isoforms  in CC were also investigated.
      LTIH markedly attenuated the erectile responses  (ICP/MAP), and these were
      partially prevented by apocynin treatment. Promoted  oxidative stress-associated
      NADPH oxidase subunit activation was found  in CC from LTIH rats. Decreased
      expression and activity of constitutive NOS  (cNOS), including endothelial NOS
      and neuronal NOS, associated with enhanced  inducible NOS (iNOS) expression and
      activity were observed in LTIH rats.  Apocynin prevented the decrease in cNOS
      activity and inhibited iNOS expression  and activity in LTIH rats. These results
      indicate that NADPH oxidase  activation plays an important role in the
      pathogenesis of LTIH-mediated  ED.

PMID- 22653965
TI  - Evaluation of testicular sperm CRISP2 as a potential target for contraception.
AB  - Cysteine-rich secretory protein 2 (CRISP2) is a testicular sperm protein 
      proposed to be involved in fertilization. With the aim of examining the 
      relevance of CRISP2 for fertility and its potential use as a target for 
      contraception, in the present work, male and female rats were immunized with 
      recombinant CRISP2 coupled to maltose-binding protein (MBP) and evaluated for 
      their subsequent fertility. As controls, animals were injected with either MBP 
      or recombinant CRISP1. Enzyme-linked immunosorbent assay of sera collected at 
      different intervals after immunization indicated that CRISP2 immunization  raised
      specific antibodies in both sexes, with levels that increased as a  function of
      time. Western blot studies revealed that anti-CRISP2 sera were  capable of
      recognizing CRISP2 in testicular, epididymal, and sperm extracts,  whereas
      histological studies showed no evidence of autoimmune orchitis or  epididymitis.
      Indirect immunofluorescence experiments revealed the ability of  anti-CRISP2 sera
      to recognize the native sperm protein in fresh, capacitated,  and ionophore
      induced acrosome-reacted cells. Moreover, anti-CRISP2 sera  significantly
      inhibited the sperm ability to penetrate zona-free eggs,  confirming the role of
      CRISP2 in rat gamete fusion. In spite of the presence  of circulating anti-CRISP2
      antibodies capable of inhibiting the sperm  fertilizing ability, mating studies
      revealed no effects of CRISP2 immunization  on male or female fertility, in
      contrast to the significant inhibition  observed in both sexes in animals
      injected with CRISP1. Together, these  observations indicated the immunogenic
      properties of testicular CRISP2 but do  not support CRISP2 as a target for
      immunocontraception or as a molecule  responsible for generating autoimmune
      orchitis or immunoinfertility.

PMID- 22653966
TI  - Oxidative stress induced by curcumin promotes the death of cutaneous T-cell
      lymphoma (HuT-78) by disrupting the function of several molecular targets.
AB  - Curcumin is known to exert its anticancer effect either by scavenging or by
      generating reactive oxygen species (ROS). In this study, we report that curcumin
      mediated rapid generation of ROS induces apoptosis by modulating different cell
      survival and cell death pathways in HuT-78 cells. Curcumin induces the activation
      of caspase-8, -2, and -9, alteration of mitochondrial membrane potential, release
      of cytochrome c, and activation of caspase-3 and concomitant PARP cleavage, but
      the addition of caspase inhibitors only partially blocked the curcumin-mediated
      apoptosis. Curcumin also downregulates the expression of antiapoptotic proteins c
      FLIP, Bcl-xL, cellular inhibitor of apoptosis protein, and X-linked IAP in a ROS
      dependent manner. Curcumin disrupts the integrity of IKK and beclin-1 by
      degrading Hsp90. Degradation of IKK leads to the inhibition of constitutive NF
      kappaB. Degradation of beclin-1 by curcumin leads to the accumulation of
      autophagy-specific marker, microtubule-associated protein-I light chain 3 (LC3),
      LC3-I. Our findings indicate that HuT-78 cells are vulnerable to oxidative stress
      induced by curcumin and as a result eventually undergo cell death.

PMID- 22653967
TI  - Characterization of the mechanism of action of the pan class I PI3K inhibitor NVP
      BKM120 across a broad range of concentrations.
AB  - The pan-phosphoinositide 3-kinase (PI3K) inhibitor BKM120 was found, at high
      concentrations, to cause cell death in various cellular systems, irrespective of
      their level of PI3K addiction. Transcriptional and biochemical profiling studies
      were used to identify the origin of these unexpected and apparently PI3K
      independent effects. At 5- to 10-fold, the concentration needed to half-maximally
      inhibit PI3K signaling. BKM120 treatment caused changes in expression of mitotic
      genes and the induction of a robust G(2)-M arrest. Tubulin polymerization assays
      and nuclear magnetic resonance-binding studies revealed that BKM120 inhibited
      microtubule dynamics upon direct binding to tubulin. To assess the contribution
      of this off-target activity vis-a-vis the antitumor activity of BKM120 in PI3K
      dependent tumors, we used a mechanistic PI3K-alpha-dependent model. We observed
      that, in vivo, daily treatment of mice with doses of BKM120 up to 40 mg/kg led to
      tumor regressions with no increase in the mitotic index. Thus, strong antitumor
      activity can be achieved in PI3K-dependent models at exposures that are below
      those necessary to engage the off-target activity. In comparison, the clinical
      data indicate that it is unlikely that BKM120 will achieve exposures sufficient
      to significantly engage the off-target activity at tolerated doses and schedules.
      However, in preclinical settings, the consequences of the off-target activity
      start to manifest themselves at concentrations above 1 MUmol/L in vitro and doses
      above 50 mg/kg in efficacy studies using subcutaneous tumor-bearing mice. Hence,
      careful concentration and dose range selection is required to ensure that any
      observation can be correctly attributed to BKM120 inhibition of PI3K.

PMID- 22653969
TI  - The checkpoint kinase inhibitor AZD7762 potentiates chemotherapy-induced
      apoptosis of p53-mutated multiple myeloma cells.
AB  - DNA cross-linking agents are frequently used in the treatment of multiple myeloma
      generating lesions, which activate checkpoint kinase 1 (Chk1), a critical
      transducer of the DNA damage response. Chk1 activation promotes cell survival by
      regulating cell-cycle arrest and DNA repair following genotoxic stress. The
      ability of AZD7762, an ATP-competitive Chk1/2 inhibitor to increase the efficacy
      of the DNA-damaging agents bendamustine, melphalan, and doxorubicin was examined
      using four human myeloma cell lines, KMS-12-BM, KMS-12-PE, RPMI-8226, and U266B1.
      The in vitro activity of AZD7762 as monotherapy and combined with alkylating
      agents and the "novel" drug bortezomib was evaluated by studying its effects on
      cytotoxicity, signaling, and apoptotic pathways. The Chk1/2 inhibitor AZD7762
      potentiated the antiproliferative effects of bendamustine, melphalan, and
      doxorubicin but not bortezomib in multiple myeloma cell lines that were p53
      deficient. Increased gammaH2AX staining in cells treated with bendamustine or
      melphalan plus AZD7762 indicates a greater degree of DNA damage with combined
      therapy. Abrogation of the G(2)-M checkpoint by AZD7762 resulted in mitotic
      catastrophe with ensuing apoptosis evidenced by PARP and caspase-3 cleavage. In
      summary, the cytotoxic effects of bendamustine, melphalan and doxorubicin on p53
      deficient multiple myeloma cell lines were enhanced by the coadministration of
      AZD7762. These data provide a rationale for testing these combinations in
      patients with relapsed and/or refractory multiple myeloma.

PMID- 22653968
TI  - Protein kinase C inhibitor AEB071 targets ocular melanoma harboring GNAQ
      mutations via effects on the PKC/Erk1/2 and PKC/NF-kappaB pathways.
AB  - Somatic GNAQ mutations at codon 209 have been identified in approximately 50% of
      uveal melanomas and have been reported to be oncogenic through activating
      PLCbeta/PKC/Erk1/2 pathways. We hypothesized that protein kinase C (PKC) may
      provide new opportunities for therapeutic targeting of uveal melanoma carrying
      GNAQ mutations. To test this hypothesis, uveal melanoma cells harboring wild-type
      or mutant GNAQ were treated with the PKC inhibitor AEB071 (sotrastaurin) or
      infected with lentivirus-expressing short hairpin RNAs (shRNA) targeting PKC
      isoforms. Notably, AEB071 at low micromolar concentrations significantly
      inhibited the growth of uveal melanoma cells harboring GNAQ mutations through
      induction of G(1) arrest and apoptosis. However, AEB071 had little effect on
      uveal melanoma cells carrying wild-type GNAQ. AEB071-mediated cell inhibition in
      the GNAQ-mutated uveal melanoma was accompanied by inhibition of extracellular
      signal-regulated kinase (Erk)1/2 phosphorylation, NF-kappaB, decreased expression
      of cyclin D1, survivin, Bcl-xL, and XIAP, and increased expression of cyclin
      dependent kinase inhibitor p27(Kip1). AEB071 suppressed the expression of PKC
      alpha, beta, delta, epsilon, and theta in GNAQ-mutated uveal melanoma cells. Our
      findings from shRNA-mediated knockdown studies revealed that these PKC isoforms
      are functionally important for uveal melanoma cells harboring GNAQ mutations.
      Furthermore, inhibitors of Erk1/2 and NF-kappaB pathways reduced viability of
      uveal melanoma cells. Together, our findings show that AEB071 exerts antitumor
      action on uveal melanoma cells carrying GNAQ mutations via targeting PKC/Erk1/2
      and PKC/NF-kappaB pathways. Targeted PKC inhibition with drugs such as AEB071
      offers novel therapeutic potential for uveal melanoma harboring GNAQ mutations.

PMID- 22653970
TI  - Long QT2 mutation on the Kv11.1 ion channel inhibits current activity by ablating
      a protein kinase Calpha consensus site.
AB  - Mutations that inhibit Kv11.1 ion channel activity contribute to abnormalities of
      cardiac repolarization that can lead to long QT2 (LQT2) cardiac arrhythmias and
      sudden death. However, for most of these mutations, nothing is known about the
      molecular mechanism linking Kv11.1 malfunction to cardiac death. We have
      previously demonstrated that disease-related mutations that create consensus
      sites for kinases on ion channels can dramatically change ion channel activity.
      Here, we show that a LQT2-associated mutation can inhibit Kv11.1 ion channel
      activity by perturbing a consensus site for the Ser/Thr protein kinase C alpha
      (PKCalpha). We first reveal by mass spectrometry analysis that Ser890 of the
      Kv11.1 ion channel is phosphorylated. Then, we demonstrate by a phospho-detection
      immunoassay combined with genetic manipulation that PKCalpha phosphorylates
      Ser890. Furthermore, we show that Ser890 phosphorylation is associated with an
      increase in Kv11.1 membrane density with alteration of recovery from
      inactivation. In addition, a newly discovered and as yet uncharacterized LQT2
      associated nonsynonymous single nucleotide polymorphism 2660 G->A within the
      human ether-a-go-go-related gene 1 coding sequence, which replaces arginine 887
      with a histidine residue (R887H), strongly inhibits PKCalpha-dependent
      phosphorylation of residue Ser890 on Kv11.1, and ultimately inhibits surface
      expression and current density. Taken together, our data provide a functional
      link between this channel mutation and LQT2.

PMID- 22653972
TI  - How I treat CML blast crisis.
AB  - Blast crisis (BC) remains the major challenge in the management of chronic
      myeloid leukemia (CML). It is now generally accepted that BC is the consequence
      of continued BCR-ABL activity leading to genetic instability, DNA damage, and
      impaired DNA repair. Most patients with BC carry multiple mutations, and up to
      80% show additional chromosomal aberrations in a nonrandom pattern. Treatment
      with tyrosine kinase inhibitors has improved survival in BC modestly, but most
      long-term survivors are those who have been transplanted. Patients in BC should
      be treated with a tyrosine kinase inhibitor according to mutation profile, with
      or without chemotherapy, with the goal of achieving a second chronic phase and
      proceeding to allogeneic stem cell transplantation as quickly as possible.
      Although long-term remissions are rare, allogeneic stem cell transplantation
      provides the best chance of a cure in BC. Investigational agents are not likely
      to provide an alternative in the near future. In view of these limited options,
      prevention of BC by a rigorous and early elimination of BCR-ABL is recommended.
      Early response indicators should be used to select patients for alternative
      therapies and early transplantation. Every attempt should be made to reduce or
      eliminate BCR-ABL consistent with good patient care as far as possible.

PMID- 22653971
TI  - Functional and pharmacological characteristics of metabotropic glutamate
      receptors 2/4 heterodimers.
AB  - Metabotropic glutamate receptors (mGluRs) were thought until recently to function
      mainly as stable homodimers, but recent work suggests that heteromerization is
      possible. Despite the growth in available compounds targeting mGluRs, little is
      known about the pharmacological profile of mGluR heterodimers. Here, this
      question was addressed for the mGluR2/4 heterodimer, examined by coexpressing
      both receptors in isolated sympathetic neurons from the rat superior cervical
      ganglion (SCG), a native neuronal system with a null mGluR background. Under
      conditions that favor mGluR2/4 heterodimer formation, activation of the receptor
      was not evident with the mGluR2-selective agonist (2S,2'R,3'R)-2-(2',3'
      dicarboxycyclopropyl)glycine (DCG-IV) or with the mGluR4 selective agonist L-(+)
      2-amino-4-phosphonobutyric acid (L-AP4); however, full activation was apparent
      when both ligands were applied together, confirming that mGluR dimers require
      ligand binding in both subunits for full activation. Properties of allosteric
      modulators were also examined, including the findings that negative allosteric
      modulators (NAMs) have two binding sites per dimer and that positive allosteric
      modulators (PAMs) have only a single site per dimer. In SCG neurons, mGluR2/4
      dimers were not inhibited by the mGluR2-selective NAM (Z)-1-[2-cycloheptyloxy-2
      (2,6-dichlorophenyl)ethenyl]-1H-1,2,4-triazole (Ro 64-5229), supporting the two
      site model. Furthermore, application of the mGluR4 selective PAMs N-(4-chloro-3
      methoxyphenyl)-2-pyridinecarboxamide (VU0361737) or N-phenyl-7
      (hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) and combined
      application of mGluR4 PAMs with the mGluR2 selective PAM biphenyl indanone-A
      failed to potentiate glutamate responses through mGluR2/4, suggesting that
      mGluR2/4 heterodimers are not modulatable by PAMs that are currently available.

PMID- 22653973
TI  - VEGFR1 stimulates a CXCR4-dependent translocation of megakaryocytes to the
      vascular niche, enhancing platelet production in mice.
AB  - It has previously been reported that VEGF-A stimulates megakaryocyte (MK)
      maturation in vitro. Here we show that treatment of mice with the isoform VEGF
      A(165) resulted in a significant increase in circulating numbers of platelets.
      Using specific VEGFR1 and VEGFR2 blocking mAbs and selective VEGFR1 and 2
      agonists, PlGF-2 and VEGF-E, respectively, we show directly that stimulation of
      VEGFR1, but not VEGFR2, increases circulating platelet numbers in vivo. Using
      flow cytometric analysis of harvested MKs, we show that while PlGF does not
      change the absolute numbers of MKs present in the bone marrow and the spleen, it
      increases both their maturation and cell-surface expression of CXCR4 in the bone
      marrow. Histology of the bone marrow revealed a redistribution of MKs from the
      endosteal to the vascular niche in response to both VEGF-A(165) and PlGF-2
      treatment in vivo. Antagonism of CXCR4 suppressed both the VEGFR1-stimulated
      redistribution of megakyocytes within the bone marrow compartment and the VEGF
      A(165)-induced thrombocytosis. In conclusion, we define a novel proinflammatory
      VEGFR1-mediated pathway that stimulates the maturation and up-regulation of CXCR4
      on megakaryocytes, leading to their redistribution within the bone marrow
      environment, thereby enhancing platelet production in vivo.

PMID- 22653974
TI  - Reconstructing the human hematopoietic niche in immunodeficient mice:
      opportunities for studying primary multiple myeloma.
AB  - Interactions within the hematopoietic niche in the BM microenvironment are
      essential for maintenance of the stem cell pool. In addition, this niche is
      thought to serve as a sanctuary site for malignant progenitors during
      chemotherapy. Therapy resistance induced by interactions with the BM
      microenvironment is a major drawback in the treatment of hematologic malignancies
      and bone-metastasizing solid tumors. To date, studying these interactions was
      hampered by the lack of adequate in vivo models that simulate the human
      situation. In the present study, we describe a unique human-mouse hybrid model
      that allows engraftment and outgrowth of normal and malignant hematopoietic
      progenitors by implementing a technology for generating a human bone environment.
      Using luciferase gene marking of patient-derived multiple myeloma cells and
      bioluminescent imaging, we were able to follow pMM cells outgrowth and to
      visualize the effect of treatment. Therapeutic interventions in this model
      resulted in equivalent drug responses as observed in the corresponding patients.
      This novel human-mouse hybrid model creates unprecedented opportunities to
      investigate species-specific microenvironmental influences on normal and
      malignant hematopoietic development, and to develop and personalize cancer
      treatment strategies.

PMID- 22653975
TI  - Coagulation biomarkers predict disease progression in SIV-infected nonhuman
      primates.
AB  - HIV infection is associated with increased risk of cardiovascular complications,
      the underlying mechanism of which remains unclear. Plasma levels of the
      coagulation biomarker D-dimer (DD) correlate with increased mortality and
      cardiovascular events in HIV-infected patients. We compared the incidence of
      cardiovascular lesions and the levels of the coagulation markers DD and thrombin
      antithrombin in pathogenic SIV infections of rhesus and pigtailed macaques (PTMs)
      and in nonpathogenic SIV infection of African green monkeys (AGMs) and sooty
      mangabeys. Hypercoagulability and cardiovascular pathology were only observed in
      pathogenic SIV infections. In PTMs infected with SIV from AGMs (SIVagm), DD
      levels were highly indicative of AIDS progression and increased mortality and
      were associated with cardiovascular lesions, pointing to SIVagm-infected PTMs as
      an ideal animal model for the study of HIV-associated cardiovascular disease. In
      pathogenic SIV infection, DD increased early after infection, was strongly
      correlated with markers of immune activation/inflammation and microbial
      translocation (MT), and was only peripherally associated with viral loads.
      Endotoxin administration to SIVagm-infected AGMs (which lack chronic SIV-induced
      MT and immune activation) resulted in significant increases of DD. Our results
      demonstrate that hypercoagulation and cardiovascular pathology are at least in
      part a consequence of excessive immune activation and MT in SIV infection.

PMID- 22653976
TI  - Bortezomib with chemotherapy is highly active in advanced B-precursor acute
      lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma
      (TACL) Study.
AB  - Therapy of relapsed pediatric acute lymphoblastic leukemia (ALL) is hampered by
      low remission rates and high toxicity, especially in second and subsequent
      relapses. Our phase 1 study, T2005-003, showed that the combination of bortezomib
      with vincristine, dexamethasone, pegylated asparaginase, and doxorubicin had
      acceptable toxicity. We report the phase 2 expansion of this combination in
      patients with relapsed ALL who failed 2-3 previous regimens. Twenty-two patients
      with relapsed ALL were treated with bortezomib combined with this regimen; their
      ages ranged from 1 to 22 years, and they had either B-precursor ALL (n = 20) or T
      cell ALL (n = 2). Grade 3 peripheral neuropathy developed in 2 (9%) patients.
      After 3 patients died from bacterial infections, treatment with vancomycin,
      levofloxacin, and voriconazole prophylaxis resulted in no further infectious
      mortality in the last 6 patients. Fourteen patients achieved complete remission
      (CR), and 2 achieved CR without platelet recovery, for an overall 73% response
      rate, meeting predefined criteria allowing for early closure. B-precursor
      patients faired best, with 16 of 20 (80%) CR + CR without platelet recovery,
      whereas the 2 patients with T-cell ALL did not respond. Thus, this combination of
      bortezomib with chemotherapy is active in B-precursor ALL, and prophylactic
      antibiotics may be useful in reducing mortality. Bortezomib merits further
      evaluation in combination therapy in pediatric B-precursor ALL. This study is
      registered at http://www.clinicaltrials.gov as NCT00440726.

PMID- 22653977
TI  - FANCL ubiquitinates beta-catenin and enhances its nuclear function.
AB  - Bone marrow failure is a nearly universal complication of Fanconi anemia. The
      proteins encoded by FANC genes are involved in DNA damage responses through the
      formation of a multisubunit nuclear complex that facilitates the E3 ubiquitin
      ligase activity of FANCL. However, it is not known whether loss of E3 ubiquitin
      ligase activity accounts for the hematopoietic stem cell defects characteristic
      of Fanconi anemia. Here we provide evidence that FANCL increases the activity and
      expression of beta-catenin, a key pluripotency factor in hematopoietic stem
      cells. We show that FANCL ubiquitinates beta-catenin with atypical ubiquitin
      chain extension known to have nonproteolytic functions. Specifically, beta
      catenin modified with lysine-11 ubiquitin chain extension efficiently activates a
      lymphocyte enhancer-binding factor-T cell factor reporter. We also show that
      FANCL-deficient cells display diminished capacity to activate beta-catenin
      leading to reduced transcription of Wnt-responsive targets c-Myc and Cyclin D1.
      Suppression of FANCL expression in normal human CD34(+) stem and progenitor cells
      results in fewer beta-catenin active cells and inhibits expansion of multilineage
      progenitors. Together, these results suggest that diminished Wnt/beta-catenin
      signaling may be an underlying molecular defect in FANCL-deficient hematopoietic
      stem cells leading to their accelerated loss.

PMID- 22653978
TI  - Protein disulfide isomerase capture during thrombus formation in vivo depends on
      the presence of beta3 integrins.
AB  - Extracellular protein disulfide isomerase (PDI) is required for platelet thrombus
      formation and fibrin generation after arteriolar wall injury in live mice. PDI is
      secreted from platelets and endothelial cells on cellular activation, but the
      mechanism of capture of secreted PDI within the injured vasculature is unknown.
      We establish that, like the endothelial beta3 integrin alpha(V)beta(3), the
      platelet integrin alpha(IIb)beta(3) binds PDI. PDI also binds to recombinant
      beta3. Using intravital microscopy, we demonstrate that PDI accumulation at the
      site of laser-induced arteriolar wall injury is markedly reduced in beta3-null
      (beta3(-/-)) mice, and neither a platelet thrombus nor fibrin is generated at the
      vessel injury site. The absence of fibrin after vascular injury in beta3(-/-)
      mice is because of the absence of extracellular PDI. To evaluate the relative
      importance of endothelial alpha(V)beta(3) versus platelet alpha(IIb)beta(3) or
      alpha(V)beta(3), we performed reciprocal bone marrow transplants on wild-type and
      beta3(-/-) mice. PDI accumulation and platelet thrombus formation were markedly
      decreased after vessel injury in wild-type mice transplanted with beta3(-/-) bone
      marrow or in beta3(-/-) mice transplanted with wild-type bone marrow. These
      results indicate that both endothelial and platelet beta3 integrins contribute to
      extracellular PDI binding at the vascular injury site.

PMID- 22653979
TI  - Pioglitazone and the risk of bladder cancer.

PMID- 22653980
TI  - Assessment of female sex as a risk factor in atrial fibrillation in Sweden:
      nationwide retrospective cohort study.
AB  - OBJECTIVE: To determine whether women with atrial fibrillation have a higher risk
      of stroke than men. DESIGN: Nationwide retrospective cohort study. SETTING:
      Patients with a diagnosis of atrial fibrillation in the Swedish hospital
      discharge register between 1 July 2005 and 31 December 2008. Information about
      drug treatment taken from the Swedish drug register. PARTICIPANTS: 100,802
      patients with atrial fibrillation at any Swedish hospital or hospital affiliated
      outpatient clinic with a total follow-up of 139,504 years at risk (median 1.2
      years). We excluded patients with warfarin at baseline, mitral stenosis, previous
      valvular surgery, or who died within 14 days from baseline. MAIN OUTCOME MEASURE:
      Incidence of ischaemic stroke. RESULTS: Ischaemic strokes were more common in
      women than in men (6.2% v 4.2% per year, P<0.0001). The univariable hazard ratio
      for women compared with men was 1.47 (95% confidence 1.40 to 1.54), indicating a
      47% higher incidence of ischaemic stroke in women than in men. Stratification
      according to the CHADS(2) scheme showed increased stroke rates for women in all
      strata. After multivariable adjustment for 35 cofactors for stroke, an increased
      risk of stroke in women remained (1.18, 1.12 to 1.24). Among patients with "lone
      atrial fibrillation" (age <65 years and no vascular disease), the annual stroke
      rate tended to be higher in women than in men, although this difference was not
      significant (0.7% v 0.5%, P=0.09). When low risk patients with CHADS(2) scores of
      0-1 were stratified according to their CHA(2)DS(2)-VASc scores, women did not
      have higher stroke incidence than men at CHA(2)DS(2)-VASc scores of 2 or less.
      CONCLUSION: Women with atrial fibrillation have a moderately increased risk of
      stroke compared with men, and thus, female sex should be considered when making
      decisions about anticoagulation treatment. However, women younger than 65 years
      and without other risk factors have a low risk for stroke, and do not need
      anticoagulant treatment.

PMID- 22653983
TI  - Female sex as a risk factor for stroke in atrial fibrillation.

PMID- 22653982
TI  - The effectiveness and cost effectiveness of dark chocolate consumption as
      prevention therapy in people at high risk of cardiovascular disease: best case
      scenario analysis using a Markov model.
AB  - OBJECTIVE: To model the long term effectiveness and cost effectiveness of daily
      dark chocolate consumption in a population with metabolic syndrome at high risk
      of cardiovascular disease. DESIGN: Best case scenario analysis using a Markov
      model. SETTING: Australian Diabetes, Obesity and Lifestyle study. PARTICIPANTS:
      2013 people with hypertension who met the criteria for metabolic syndrome, with
      no history of cardiovascular disease and not receiving antihypertensive therapy.
      MAIN OUTCOME MEASURES: Treatment effects associated with dark chocolate
      consumption derived from published meta-analyses were used to determine the
      absolute number of cardiovascular events with and without treatment. Costs
      associated with cardiovascular events and treatments were applied to determine
      the potential amount of funding required for dark chocolate therapy to be
      considered cost effective. RESULTS: Daily consumption of dark chocolate
      (polyphenol content equivalent to 100 g of dark chocolate) can reduce
      cardiovascular events by 85 (95% confidence interval 60 to 105) per 10,000
      population treated over 10 years. $A40 (L25; ?31; $42) could be cost effectively
      spent per person per year on prevention strategies using dark chocolate. These
      results assume 100% compliance and represent a best case scenario. CONCLUSIONS:
      The blood pressure and cholesterol lowering effects of dark chocolate consumption
      are beneficial in the prevention of cardiovascular events in a population with
      metabolic syndrome. Daily dark chocolate consumption could be an effective
      cardiovascular preventive strategy in this population.

PMID- 22653981
TI  - The use of pioglitazone and the risk of bladder cancer in people with type 2
      diabetes: nested case-control study.
AB  - OBJECTIVE: To determine if the use of pioglitazone is associated with an
      increased risk of incident bladder cancer in people with type 2 diabetes. DESIGN:
      Retrospective cohort study using a nested case-control analysis. SETTING: Over
      600 general practices in the United Kingdom contributing to the general practice
      research database. PARTICIPANTS: The cohort consisted of people with type 2
      diabetes who were newly treated with oral hypoglycaemic agents between 1 January
      1988 and 31 December 2009. All incident cases of bladder cancer occurring during
      follow-up were identified and matched to up to 20 controls on year of birth, year
      of cohort entry, sex, and duration of follow-up. Exposure was defined as ever use
      of pioglitazone, along with measures of duration and cumulative dosage. MAIN
      OUTCOME MEASURE: Risk of incident bladder cancer associated with use of
      pioglitazone. RESULTS: The cohort included 115,727 new users of oral
      hypoglycaemic agents, with 470 patients diagnosed as having bladder cancer during
      follow-up (rate 89.4 per 100,000 person years). The 376 cases of bladder cancer
      that were diagnosed beyond one year of follow-up were matched to 6699 controls.
      Overall, ever use of pioglitazone was associated with an increased rate of
      bladder cancer (rate ratio 1.83, 95% confidence interval 1.10 to 3.05). The rate
      increased as a function of duration of use, with the highest rate observed in
      patients exposed for more than 24 months (1.99, 1.14 to 3.45) and in those with a
      cumulative dosage greater than 28,000 mg (2.54, 1.05 to 6.14). CONCLUSION: The
      use of pioglitazone is associated with an increased risk of incident bladder
      cancer among people with type 2 diabetes.

PMID- 22653984
TI  - The kinetics of highly sensitive cardiac troponin T release after prolonged
      treadmill exercise in adolescent and adult athletes.
AB  - The nature and kinetics of postexercise cardiac troponin (cTn) appearance is
      poorly described and understood in most athlete populations. We compared the
      kinetics of high-sensitivity cTn T (hs-cTnT) after endurance running in training
      matched adolescents and adults. Thirteen male adolescent (mean age: 14.1 +/- 1.1
      yr) and 13 male adult (24.0 +/- 3.6 yr) runners performed a 90-min constant-load
      treadmill run at 95% of ventilatory threshold. Serum hs-cTnT levels were assessed
      preexercise, immediately postexercise, and at 1, 2, 3, 4, 5, 6, and 24 h
      postexercise. Serum NH(2)-terminal pro-brain natriuretic peptide (NT-pro-BNP)
      levels were recorded preexercise and 3, 6, and 24 h postexercise. Left
      ventricular function was assessed preexercise, immediately postexercise, and 6 h
      postexercise. Peak hs-cTnT occurred at 3-4 h postexercise in all subjects, but
      was substantially higher (P < 0.05) in adolescents [median (range): 211.0 (11.2
      794.5) ng/l] compared with adults [median (range): 19.1 (9.7-305.6) ng/l]. Peak
      hs-cTnT was followed by a rapid decrease in both groups, although adolescent data
      had not returned to baseline at 24 h. Substantial interindividual variability was
      noted in peak hs-cTnT, especially in the adolescents. NT-pro-BNP was
      significantly elevated postexercise in both adults and adolescents and remained
      above baseline at 24 h in both groups. In both groups, left ventricular ejection
      fraction and the ratio of early-to-atrial peak Doppler flow velocities were
      significantly decreased immediately postexercise. Peak hs-cTnT was not related to
      changes in ejection fraction, ratio of early-to-atrial peak Doppler flow
      velocities, or NT-pro-BNP. The present data suggest that postexercise hs-cTnT
      elevation 1) occurred in all runners, 2) peaked 3-4 h postexercise, and 3) the
      peak hs-cTnT concentration after prolonged exercise was higher in adolescents
      than adults.

PMID- 22653985
TI  - Viewpoint: Are there valid concerns for completing a marathon at 39 weeks of
      pregnancy?

PMID- 22653987
TI  - Effect of oxygen breathing on micro oxygen bubbles in nitrogen-depleted rat
      adipose tissue at sea level and 25 kPa altitude exposures.
AB  - The standard treatment of altitude decompression sickness (aDCS) caused by
      nitrogen bubble formation is oxygen breathing and recompression. However, micro
      air bubbles (containing 79% nitrogen), injected into adipose tissue, grow and
      stabilize at 25 kPa regardless of continued oxygen breathing and the tissue
      nitrogen pressure. To quantify the contribution of oxygen to bubble growth at
      altitude, micro oxygen bubbles (containing 0% nitrogen) were injected into the
      adipose tissue of rats depleted from nitrogen by means of preoxygenation
      (fraction of inspired oxygen = 1.0; 100%) and the bubbles studied at 101.3 kPa
      (sea level) or at 25 kPa altitude exposures during continued oxygen breathing. In
      keeping with previous observations and bubble kinetic models, we hypothesize that
      oxygen breathing may contribute to oxygen bubble growth at altitude. Anesthetized
      rats were exposed to 3 h of oxygen prebreathing at 101.3 kPa (sea level). Micro
      oxygen bubbles of 500-800 nl were then injected into the exposed abdominal
      adipose tissue. The oxygen bubbles were studied for up to 3.5 h during continued
      oxygen breathing at either 101.3 or 25 kPa ambient pressures. At 101.3 kPa, all
      bubbles shrank consistently until they disappeared from view at a net
      disappearance rate (0.02 mm(2) * min(-1)) significantly faster than for similar
      bubbles at 25 kPa altitude (0.01 mm(2) * min(-1)). At 25 kPa, most bubbles
      initially grew for 2-40 min, after which they shrank and disappeared. Four
      bubbles did not disappear while at 25 kPa. The results support bubble kinetic
      models based on Fick's first law of diffusion, Boyles law, and the oxygen window
      effect, predicting that oxygen contributes more to bubble volume and growth
      during hypobaric conditions. As the effect of oxygen increases, the lower the
      ambient pressure. The results indicate that recompression is instrumental in the
      treatment of aDCS.

PMID- 22653986
TI  - WISE 2005: responses of women to sublingual nitroglycerin before and after 56
      days of 6 degrees  head-down bed rest.
AB  - This study tested the hypothesis that cardiovascular effects of sublingual
      nitroglycerin (NG) would be exaggerated after 56 days of 6 degrees  head-down bed
      rest (HDBR) in women, and that an aerobic and resistive exercise countermeasure
      (EX, n = 8) would reduce the effect compared with HDBR without exercise (CON, n =
      7). Middle cerebral artery maximal blood flow velocity (CBFV), cardiac stroke
      volume (SV), and superficial femoral artery blood flow (Doppler ultrasound) were
      recorded at baseline rest and for 5 min following 0.3 mg sublingual NG. Post
      HDBR, NG caused greater increases in heart rate (HR) in CON compared with EX
      (+24.9 +/- 7.7 and +18.8 +/- 6.6 beats/min, respectively, P < 0.0001). The
      increase in HR combined with reductions in SV to maintain cardiac output.
      Systolic, mean, and pulse pressures were reduced 5-10 mmHg by NG, but total
      peripheral resistance was only slightly reduced at 3 min after NG. Reductions in
      CBFV of -12.5 +/- 3.8 cm/s were seen after NG, but a reduction in the Doppler
      resistance index suggested dilation of the middle cerebral artery with no
      differences after HDBR. The femoral artery dilated with NG and blood flow was
      reduced ~50% with the appearance of large negative waves suggesting a marked
      increase in downstream resistance, but there were no effects of HDBR. In general,
      responses of women to NG were not altered by HDBR; the greater increase in HR in
      CON but not EX was probably a consequence of cardiovascular deconditioning. These
      results contrast with the hypothesis and a previous investigation of men after
      HDBR by revealing no change in cardiovascular responses to exogenous nitric
      oxide.

PMID- 22653988
TI  - Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and
      increases exercise endurance.
AB  - Statins are cholesterol-lowering drugs widely used in the prevention of
      cardiovascular diseases; however, they are associated with various types of
      myopathies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase and thus decrease biosynthesis of low-density lipoprotein cholesterol
      and may also reduce ubiquinones, essential coenzymes of a mitochondrial electron
      transport chain, which contain isoprenoid residues, synthesized through an HMG
      CoA reductase-dependent pathway. Therefore, we hypothesized that statin treatment
      might influence physical performance through muscular mitochondrial dysfunction
      due to ubiquinone deficiency. The effect of two statins, atorvastatin and
      pravastatin, on ubiquinone content, mitochondrial function, and physical
      performance was examined by using statin-treated mice. Changes in energy
      metabolism in association with statin treatment were studied by using cultured
      myocytes. We found that atorvastatin-treated mice developed muscular
      mitochondrial dysfunction due to ubiquinone deficiency and a decrease in exercise
      endurance without affecting muscle mass and strength. Meanwhile, pravastatin at
      ten times higher dose of atorvastatin had no such effects. In cultured myocytes,
      atorvastatin-related decrease in mitochondrial activity led to a decrease in
      oxygen utilization and an increase in lactate production. Conversely, coenzyme
      Q(10) treatment in atorvastatin-treated mice reversed atorvastatin-related
      mitochondrial dysfunction and a decrease in oxygen utilization, and thus improved
      exercise endurance. Atorvastatin decreased exercise endurance in mice through
      mitochondrial dysfunction due to ubiquinone deficiency. Ubiquinone
      supplementation with coenzyme Q(10) could reverse atorvastatin-related
      mitochondrial dysfunction and decrease in exercise tolerance.

PMID- 22653990
TI  - Effects of voluntary running on oxygen consumption, RQ, and energy expenditure
      during primary prevention of diet-induced obesity in C57BL/6N mice.
AB  - Diet-induced obesity (DIO) in C57BL/6 mice is the standard model for studying
      obesity in mice. The few reports of DIO utilizing voluntary running provide
      contradictory results with respect to prevention of obesity. However, total
      energy expenditures associated with voluntary running during DIO are unknown. We
      hypothesized that voluntary running would increase the amount of total energy
      expended during DIO. Female C57BL/6N mice were randomly assigned to one of three
      experimental groups [high-fat diet with voluntary running (HFRun); high-fat diet
      without running (HFSed); and low-fat diet without running (LFSed)] for a 10-wk
      period. We confirmed production of obesity in HFSed, and more importantly
      demonstrated primary prevention of obesity by voluntary running in a group of
      cohorts (HFRun). Indirect calorimetry was performed to determine oxygen
      consumption (Vo(2)) and respiratory quotient (RQ). The following novel mechanisms
      were identified in female C57BL/6N mice: 1) HFRun showed ~2 times greater total
      energy expenditures during a day compared with HFSed and LFSed; 2) HFRun had
      increased Vo(2) compared with HFSed and LFSed, lower RQ in the light period than
      HFSed, and lower RQ in both light and dark periods than LFSed; and 3) in the
      HFRun group, the magnitude of change in Vo(2) and RQ differed in dark and light
      periods during voluntary running. Our data combined with existing literature
      point to a potential threshold of physical activity that would prevent DIO in
      this mouse model. These data give a mechanistic explanation to resolve
      contradictory reports on whether voluntary running can prevent obesity in the DIO
      mouse model. In conclusion, voluntary running rescues high-fat fed, female
      C57BL/6N mice from obesity in DIO by doubling energy expenditure during the dark
      period and significantly increasing energy expenditure during the light cycle.

PMID- 22653989
TI  - What can computed tomography and magnetic resonance imaging tell us about
      ventilation?
AB  - This review provides a summary of pulmonary functional imaging approaches for
      determining pulmonary ventilation, with a specific focus on multi-detector x-ray
      computed tomography and magnetic resonance imaging (MRI). We provide the
      important functional definitions of pulmonary ventilation typically used in
      medicine and physiology and discuss the fact that some of the imaging literature
      describes gas distribution abnormalities in pulmonary disease that may or may not
      be related to the physiological definition or clinical interpretation of
      ventilation. We also review the current state-of-the-field in terms of the key
      physiological questions yet unanswered related to ventilation and gas
      distribution in lung disease. Current and emerging imaging research methods are
      described, including their strengths and the challenges that remain to translate
      these methods to more wide-spread research and clinical use. We also examine how
      computed tomography and MRI might be used in the future to gain more insight into
      gas distribution and ventilation abnormalities in pulmonary disease.

PMID- 22653991
TI  - Diminished muscle growth in the obese Zucker rat following overload is associated
      with hyperphosphorylation of AMPK and dsRNA-dependent protein kinase.
AB  - Previous data have suggested that insulin-resistant skeletal muscle may exhibit a
      diminished ability to undergo hypertrophy and that this result may be mediated,
      at least in part, from decrements in mammalian target of rapamycin (mTOR)
      signaling (Katta A, Kundla S, Kakarla SK, Wu M, Fannin J, Paturi S, Liu H,
      Addagarla HS, Blough ER. Am J Physiol Regul Integr Comp Physiol 299: R1666-R1675,
      2010). Herein, we attempt to extend these observations by determining if this
      attenuation in muscle growth is associated with alterations in AMP-activated
      protein kinase (AMPK) signaling, an upstream mediator of mTOR, and changes in the
      activation of dsRNA-dependent protein kinase (PKR), which functions as an
      inhibitor of protein synthesis and potential mediator of protein degradation.
      Compared with that observed in lean Zucker (LZ) rats, the phosphorylation of
      AMPKalpha at Thr172 was higher after 3 wk of overload in the insulin-resistant
      obese Zucker (OZ) soleus (P < 0.05). This change in AMPKalpha phosphorylation was
      accompanied by increases in the amount of phosphorylated PKR (Thr446), elevations
      in the PKR-dependent phosphorylation of eukaryotic initiation factor (eIF)-2alpha
      (Ser51), augmented p38 MAP kinase (Thr180/Tyr182) phosphorylation, and increases
      in the amount of protein ubiquitination (P < 0.05). Taken together, these results
      suggest that the diminished hypertrophic response we observe in the OZ rat may be
      mediated, at least in part, by the hyperactivation of AMPK- and PKR-related
      signaling.

PMID- 22653993
TI  - A novel cardiopulmonary exercise test protocol and criterion to determine maximal
      oxygen uptake in chronic heart failure.
AB  - Cardiopulmonary exercise testing for peak oxygen uptake (Vo(2peak)) can evaluate
      prognosis in chronic heart failure (CHF) patients, with the peak respiratory
      exchange ratio (RER(peak)) commonly used to confirm maximal effort and maximal
      oxygen uptake (Vo(2max)). We determined the precision of RER(peak) in confirming
      Vo(2max), and whether a novel ramp-incremental (RI) step-exercise (SE) (RISE)
      test could better determine Vo(2max) in CHF. Male CHF patients (n = 24; NYHA
      class I-III) performed a symptom-limited RISE-95 cycle ergometer test in the
      format: RI (4-18 W/min; ~10 min); 5 min recovery (10 W); SE (95% peak RI work
      rate). Patients (n = 18) then performed RISE-95 tests using slow (3-8 W/min; ~15
      min) and fast (10-30 W/min; ~6 min) ramp rates. Pulmonary gas exchange was
      measured breath-by-breath. Vo(2peak) was compared within patients by unpaired t
      test of the highest 12 breaths during RI and SE phases to confirm Vo(2max) and
      its 95% confidence limits (CI(95)). RER(peak) was significantly influenced by
      ramp rate (fast, medium, slow: 1.21 +/- 0.1 vs. 1.15 +/- 0.1 vs. 1.09 +/- 0.1; P
      = 0.001), unlike Vo(2peak) (mean n = 18; 14.4 +/- 2.6 ml.kg(-1).min(-1); P =
      0.476). Group Vo(2peak) was similar between RI and SE (n = 24; 14.5 +/- 3.0 vs.
      14.7 +/- 3.1 ml.kg(-1).min(-1); P = 0.407); however, within-subject comparisons
      confirmed Vo(2max) in only 14 of 24 patients (CI(95) for Vo(2max) estimation
      averaged 1.4 +/- 0.8 ml.kg(-1).min(-1)). The RER(peak) in CHF was significantly
      influenced by ramp rate, suggesting its use to determine maximal effort and
      Vo(2max) be abandoned. In contrast, the RISE-95 test had high precision for
      Vo(2max) confirmation with patient-specific CI(95) (without secondary criteria),
      and showed that Vo(2max) is commonly underestimated in CHF. The RISE-95 test was
      well tolerated by CHF patients, supporting its use for Vo(2max) confirmation.

PMID- 22653992
TI  - Ischemia reperfusion injury, KATP channels, and exercise-induced cardioprotection
      against apoptosis.
AB  - Exercise is a potent stimulus against cardiac ischemia reperfusion (IR) injury,
      although the protective mechanisms are not completely understood. The study
      purpose was to examine whether the mitochondrial or sarcolemmal ATP-sensitive
      potassium channel (mito K(ATP) or sarc K(ATP), respectively) mediates exercise
      induced cardioprotection against post-IR cell death and apoptosis. Eighty-six, 4
      mo-old male Sprague Dawley rats were randomly assigned to treadmill exercise (Ex;
      30 m/min, 3 days, 60 min, ~70 maximal oxygen uptake) and sedentary (Sed)
      treatments. Rats were exposed to regional cardiac ischemia (50 min) and
      reperfusion (120 min) or Sham (170 min; no ligation) surgeries. Exercise
      subgroups received placebo (saline), 5-hydroxydecanoate (5HD; 10 mg/kg ip), or
      HMR1098 (10 mg/kg ip) to inhibit mito K(ATP) or sarc K(ATP) channel.
      Comprehensive outcome assessments included post-IR ECG arrhythmias, cardiac
      tissue necrosis, redox perturbations, and autophagy biomarkers. No arrhythmia
      differences existed between exercised and sedentary hearts following extended
      duration IR (P < 0.05). The sarc K(ATP) channel was confirmed essential (P =
      0.002) for prevention of antinecrotic tissue death with exercise (percent
      infarct, Sed = 42%; Ex = 20%; Ex5HD = 16%; ExHMR = 42%), although neither the
      mito K(ATP) (P = 0.177) nor sarc K(ATP) (P = 0.274) channel provided post-IR
      protection against apoptosis (terminal deoxynucleotidyl transferase deoxy UTP
      mediated nick-end labeling-positive nuclei/mm(2), Sham = 1.8 +/- 0.5; Sed = 19.4
      +/- 6.7; Ex = 7.5 +/- 4.6; Ex5HD = 14.0 +/- 3.9; ExHMR = 11.1 +/- 1.8). Exercise
      preconditioning also appears to preserve basal autophagy levels, as assessed by
      Beclin 1 (P <= 0.001), microtubule-associated protein-1 light-chain 3B ratios (P
      = 0.020), and P62 (P <= 0.001), in the hours immediately following IR. Further
      research is needed to better understand these findings and corresponding redox
      changes in exercised hearts.

PMID- 22653996
TI  - In medicine we are privileged to treat our fellow humans. Introduction.

PMID- 22653997
TI  - Commentary on 'Accuracy of the skyline view for detecting dorsal cortical
      penetration during volar distal radius fixation' by A.P. Riddick, B. Hickey, and
      S.P. White. J Hand Surg Eur. 2012, 37: 407-11.

PMID- 22653994
TI  - Mitochondrial antioxidative capacity regulates muscle glucose uptake in the
      conscious mouse: effect of exercise and diet.
AB  - The objective of this study was to test the hypothesis that exercise-stimulated
      muscle glucose uptake (MGU) is augmented by increasing mitochondrial reactive
      oxygen species (mtROS) scavenging capacity. This hypothesis was tested in
      genetically altered mice fed chow or a high-fat (HF) diet that accelerates mtROS
      formation. Mice overexpressing SOD2 (sod2(Tg)), mitochondria-targeted catalase
      (mcat(Tg)), and combined SOD2 and mCAT (mtAO) were used to increase mtROS
      scavenging. mtROS was assessed by the H(2)O(2) emitting potential (JH(2)O(2)) in
      muscle fibers. sod2(Tg) did not decrease JH(2)O(2) in chow-fed mice, but
      decreased JH(2)O(2) in HF-fed mice. mcat(Tg) and mtAO decreased JH(2)O(2) in both
      chow- and HF-fed mice. In parallel, the ratio of reduced to oxidized glutathione
      (GSH/GSSG) was unaltered in sod2(Tg) in chow-fed mice, but was increased in HF
      fed sod2(Tg) and both chow- and HF-fed mcat(Tg) and mtAO. Nitrotyrosine, a marker
      of NO-dependent, reactive nitrogen species (RNS)-induced nitrative stress, was
      decreased in both chow- and HF-fed sod2(Tg), mcat(Tg), and mtAO mice. This effect
      was not changed with exercise. Kg, an index of MGU was assessed using 2-[(14)C]
      deoxyglucose during exercise. In chow-fed mice, sod2(Tg), mcat(Tg), and mtAO
      increased exercise Kg compared with wild types. Exercise Kg was also augmented in
      HF-fed sod2(Tg) and mcat(Tg) mice but unchanged in HF-fed mtAO mice. In
      conclusion, mtROS scavenging is a key regulator of exercise-mediated MGU and this
      regulation depends on nutritional state.

PMID- 22653998
TI  - Commentary on 'Early CT for suspected occult scaphoid fractures' by Stevenson et
      al. J Hand Surg Eur. 2012, 37: 447-51.

PMID- 22654000
TI  - CORESS (Confidential Reporting System for Surgery) specialty report.

PMID- 22653999
TI  - The Paul R. Manske Award for the best upper extremity congenital research
      manuscript.

PMID- 22654002
TI  - Bronchoscopic lung volume reduction for emphysema: where next?

PMID- 22654003
TI  - Multidrug-resistant tuberculosis in Eastern Europe: still on the increase?

PMID- 22654004
TI  - Pre-implantation genetic testing for hereditary pulmonary arterial hypertension:
      promise and caution.

PMID- 22654005
TI  - Respiratory critical care HERMES syllabus: defining competencies for respiratory
      doctors.

PMID- 22654006
TI  - Multicentre European study for the treatment of advanced emphysema with bronchial
      valves.
AB  - This multicentre, blinded, sham-controlled study was performed to assess the
      safety and effectiveness of bronchial valve therapy using a bilateral upper lobe
      treatment approach without the goal of lobar atelectasis. Patients with upper
      lobe predominant severe emphysema were randomised to bronchoscopy with (n = 37)
      or without (n = 36) IBV Valves for a 3-month blinded phase. A positive responder
      was defined as having both a >= 4-point improvement in St George's Respiratory
      Questionnaire (SGRQ) and a lobar volume shift as measured by quantitative
      computed tomography. At 3 months, there were eight (24%) positive responders in
      the treated group versus none (0%) in the control group (p = 0.002). Also, there
      was a significant shift in volume in the treated group from the upper lobes (mean
      +/- SD -7.3 +/- 9.0%) to the non-treated lobes (6.7 +/- 14.5%), with minimal
      change in the control group (p<0.05). Mean SGRQ total score improved in both
      groups (treatment: -4.3 +/- 16.2; control: -3.6 +/- 10.7). The procedure and
      devices were well tolerated and there were no differences in adverse events
      reported in the treatment and control groups. Treatment with bronchial valves
      without complete lobar occlusion in both upper lobes was safe, but not effective
      in the majority of patients.

PMID- 22654007
TI  - Pre-implantation genetic diagnosis in pulmonary arterial hypertension due to
      BMPR2 mutation.

PMID- 22654009
TI  - Monitoring of tobramycin levels in patients with cystic fibrosis by finger-prick
      sampling.

PMID- 22654008
TI  - Increased arterial stiffness in children with cystic fibrosis.

PMID- 22654010
TI  - Noninvasive ventilation in cystic fibrosis: the Italian physiotherapists' point
      of view.

PMID- 22654011
TI  - Penicillium marneffei presenting as an obstructing endobronchial lesion in an
      immunocompetent host.

PMID- 22654012
TI  - Surfactant protein A in chronic extrinsic allergic alveolitis.

PMID- 22654013
TI  - Supine volume drop and diaphragmatic function in adults with Pompe disease.

PMID- 22654014
TI  - Acute exacerbations of COPD: it's the weekend but it can't wait until Monday.

PMID- 22654015
TI  - Could neutrophilic airway inflammation in obese people be more due to obstructive
      sleep apnoea syndrome than to asthma?

PMID- 22654016
TI  - EBUS-TBNA in the differential diagnosis of pulmonary artery sarcoma and
      thromboembolism.

PMID- 22654020
TI  - Competitions to support STEM.

PMID- 22654025
TI  - Radio astronomy. Telescope project splits array to avoid division.

PMID- 22654017
TI  - Nomogram to predict the presence of EGFR activating mutation in lung
      adenocarcinoma.

PMID- 22654026
TI  - Archaeology. Early dates for artistic Europeans.

PMID- 22654027
TI  - Astronomy. Creative deal gives NASA telescope new lease on life.

PMID- 22654028
TI  - Psychiatry. Criticism continues to dog psychiatric manual as deadline approaches.

PMID- 22654029
TI  - Mysteries of astronomy.

PMID- 22654030
TI  - Astronomy. What is dark energy?

PMID- 22654031
TI  - Astronomy. How hot is dark matter?

PMID- 22654032
TI  - Astronomy. Where are the missing baryons?

PMID- 22654033
TI  - Astronomy. How do stars explode?

PMID- 22654034
TI  - Astronomy. What reionized the universe?

PMID- 22654035
TI  - Astronomy. What's the source of the most energetic cosmic rays?

PMID- 22654036
TI  - Astronomy. Why is the solar system so bizarre?

PMID- 22654037
TI  - Astronomy. Why is the sun's corona so hot?

PMID- 22654038
TI  - Reading too much into baboon skills?

PMID- 22654040
TI  - Going to bat for an endangered species.

PMID- 22654041
TI  - Biosecurity on thin ice in Antarctica.

PMID- 22654043
TI  - Medicine. The ultimate genetic test.

PMID- 22654044
TI  - Medicine. Whole-genome sequencing: the new standard of care?

PMID- 22654045
TI  - Evolution. Efficiency in evolutionary trade-offs.

PMID- 22654046
TI  - Geochemistry. Tracking the Fukushima radionuclides.

PMID- 22654047
TI  - Geology. Understanding sediments--reducing tsunami risk.

PMID- 22654048
TI  - Immunology. When less signaling is more.

PMID- 22654049
TI  - Physics. Speeding up quantum field theories.

PMID- 22654050
TI  - Designing cell-compatible hydrogels for biomedical applications.
AB  - Hydrogels are polymeric materials distinguished by high water content and diverse
      physical properties. They can be engineered to resemble the extracellular
      environment of the body's tissues in ways that enable their use in medical
      implants, biosensors, and drug-delivery devices. Cell-compatible hydrogels are
      designed by using a strategy of coordinated control over physical properties and
      bioactivity to influence specific interactions with cellular systems, including
      spatial and temporal patterns of biochemical and biomechanical cues known to
      modulate cell behavior. Important new discoveries in stem cell research, cancer
      biology, and cellular morphogenesis have been realized with model hydrogel
      systems premised on these designs. Basic and clinical applications for hydrogels
      in cell therapy, tissue engineering, and biomedical research continue to drive
      design improvements using performance-based materials engineering paradigms.

PMID- 22654051
TI  - Structure of a 16-nm cage designed by using protein oligomers.
AB  - Designing protein molecules that will assemble into various kinds of ordered
      materials represents an important challenge in nanotechnology. We report the
      crystal structure of a 12-subunit protein cage that self-assembles by design to
      form a tetrahedral structure roughly 16 nanometers in diameter. The strategy of
      fusing together oligomeric protein domains can be generalized to produce other
      kinds of cages or extended materials.

PMID- 22654053
TI  - Tracking Cooper pairs in a cuprate superconductor by ultrafast angle-resolved
      photoemission.
AB  - In high-temperature superconductivity, the process that leads to the formation of
      Cooper pairs, the fundamental charge carriers in any superconductor, remains
      mysterious. We used a femtosecond laser pump pulse to perturb superconducting
      Bi(2)Sr(2)CaCu(2)O(8+delta) and studied subsequent dynamics using time- and angle
      resolved photoemission and infrared reflectivity probes. Gap and quasiparticle
      population dynamics revealed marked dependencies on both excitation density and
      crystal momentum. Close to the d-wave nodes, the superconducting gap was
      sensitive to the pump intensity, and Cooper pairs recombined slowly. Far from the
      nodes, pumping affected the gap only weakly, and recombination processes were
      faster. These results demonstrate a new window into the dynamical processes that
      govern quasiparticle recombination and gap formation in cuprates.

PMID- 22654052
TI  - Quantum algorithms for quantum field theories.
AB  - Quantum field theory reconciles quantum mechanics and special relativity, and
      plays a central role in many areas of physics. We developed a quantum algorithm
      to compute relativistic scattering probabilities in a massive quantum field
      theory with quartic self-interactions (phi(4) theory) in spacetime of four and
      fewer dimensions. Its run time is polynomial in the number of particles, their
      energy, and the desired precision, and applies at both weak and strong coupling.
      In the strong-coupling and high-precision regimes, our quantum algorithm achieves
      exponential speedup over the fastest known classical algorithm.

PMID- 22654054
TI  - Tailoring electrical transport across grain boundaries in polycrystalline
      graphene.
AB  - Graphene produced by chemical vapor deposition (CVD) is polycrystalline, and
      scattering of charge carriers at grain boundaries (GBs) could degrade its
      performance relative to exfoliated, single-crystal graphene. However, the
      electrical properties of GBs have so far been addressed indirectly without
      simultaneous knowledge of their locations and structures. We present electrical
      measurements on individual GBs in CVD graphene first imaged by transmission
      electron microscopy. Unexpectedly, the electrical conductance improves by one
      order of magnitude for GBs with better interdomain connectivity. Our study
      suggests that polycrystalline graphene with good stitching may allow for
      uniformly high electrical performance rivaling that of exfoliated samples, which
      we demonstrate using optimized growth conditions and device geometry.

PMID- 22654055
TI  - Theory untangles the high-resolution infrared spectrum of the ortho-H2-CO van der
      Waals complex.
AB  - Rovibrational spectroscopy of molecules boasts extremely high precision, but its
      usefulness relies on the assignment of spectral features to corresponding quantum
      mechanical transitions. In the case of ortho-H(2)-CO, a weakly bound complex
      abundant in the interstellar medium (although not yet observed there), the rather
      complex spectrum has been unexplained for more than a decade. We assigned this
      spectrum by comparison with a purely ab initio calculation. For most lines,
      agreement to within 0.01 centimeter(-1) between experiment and theory was
      achieved. Our results show that the applicability of rovibrational spectroscopy
      can be extended with the assistance of high-accuracy quantum mechanical
      computations.

PMID- 22654056
TI  - Evolution of a vertebrate social decision-making network.
AB  - Animals evaluate and respond to their social environment with adaptive decisions.
      Revealing the neural mechanisms of such decisions is a major goal in biology. We
      analyzed expression profiles for 10 neurochemical genes across 12 brain regions
      important for decision-making in 88 species representing five vertebrate
      lineages. We found that behaviorally relevant brain regions are remarkably
      conserved over 450 million years of evolution. We also find evidence that
      different brain regions have experienced different selection pressures, because
      spatial distribution of neuroendocrine ligands are more flexible than their
      receptors across vertebrates. Our analysis suggests that the diversity of social
      behavior in vertebrates can be explained, in part, by variations on a theme of
      conserved neural and gene expression networks.

PMID- 22654057
TI  - Chitin-induced dimerization activates a plant immune receptor.
AB  - Pattern recognition receptors confer plant resistance to pathogen infection by
      recognizing the conserved pathogen-associated molecular patterns. The cell
      surface receptor chitin elicitor receptor kinase 1 of Arabidopsis (AtCERK1)
      directly binds chitin through its lysine motif (LysM)-containing ectodomain
      (AtCERK1-ECD) to activate immune responses. The crystal structure that we solved
      of an AtCERK1-ECD complexed with a chitin pentamer reveals that their interaction
      is primarily mediated by a LysM and three chitin residues. By acting as a
      bivalent ligand, a chitin octamer induces AtCERK1-ECD dimerization that is
      inhibited by shorter chitin oligomers. A mutation attenuating chitin-induced
      AtCERK1-ECD dimerization or formation of nonproductive AtCERK1 dimer by
      overexpression of AtCERK1-ECD compromises AtCERK1-mediated signaling in plant
      cells. Together, our data support the notion that chitin-induced AtCERK1
      dimerization is critical for its activation.

PMID- 22654058
TI  - Rocket launcher mechanism of collaborative actin assembly defined by single
      molecule imaging.
AB  - Interacting sets of actin assembly factors work together in cells, but the
      underlying mechanisms have remained obscure. We used triple-color single-molecule
      fluorescence microscopy to image the tumor suppressor adenomatous polyposis coli
      (APC) and the formin mDia1 during filament assembly. Complexes consisting of APC,
      mDia1, and actin monomers initiated actin filament formation, overcoming
      inhibition by capping protein and profilin. Upon filament polymerization, the
      complexes separated, with mDia1 moving processively on growing barbed ends while
      APC remained at the site of nucleation. Thus, the two assembly factors directly
      interact to initiate filament assembly and then separate but retain independent
      associations with either end of the growing filament.

PMID- 22654059
TI  - The amyloid precursor protein has a flexible transmembrane domain and binds
      cholesterol.
AB  - C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor
      protein that is cleaved by gamma-secretase to release the amyloid-beta
      polypeptides, which are associated with Alzheimer's disease. Nuclear magnetic
      resonance and electron paramagnetic resonance spectroscopy show that the
      extracellular amino terminus of C99 includes a surface-embedded "N-helix"
      followed by a short "N-loop" connecting to the transmembrane domain (TMD). The
      TMD is a flexibly curved alpha helix, making it well suited for processive
      cleavage by gamma-secretase. Titration of C99 reveals a binding site for
      cholesterol, providing mechanistic insight into how cholesterol promotes
      amyloidogenesis. Membrane-buried GXXXG motifs (G, Gly; X, any amino acid), which
      have an established role in oligomerization, were also shown to play a key role
      in cholesterol binding. The structure and cholesterol binding properties of C99
      may aid in the design of Alzheimer's therapeutics.

PMID- 22654060
TI  - Computational design of self-assembling protein nanomaterials with atomic level
      accuracy.
AB  - We describe a general computational method for designing proteins that self
      assemble to a desired symmetric architecture. Protein building blocks are docked
      together symmetrically to identify complementary packing arrangements, and low
      energy protein-protein interfaces are then designed between the building blocks
      in order to drive self-assembly. We used trimeric protein building blocks to
      design a 24-subunit, 13-nm diameter complex with octahedral symmetry and a 12
      subunit, 11-nm diameter complex with tetrahedral symmetry. The designed proteins
      assembled to the desired oligomeric states in solution, and the crystal
      structures of the complexes revealed that the resulting materials closely match
      the design models. The method can be used to design a wide variety of self
      assembling protein nanomaterials.

PMID- 22654061
TI  - Generic indicators for loss of resilience before a tipping point leading to
      population collapse.
AB  - Theory predicts that the approach of catastrophic thresholds in natural systems
      (e.g., ecosystems, the climate) may result in an increasingly slow recovery from
      small perturbations, a phenomenon called critical slowing down. We used replicate
      laboratory populations of the budding yeast Saccharomyces cerevisiae for direct
      observation of critical slowing down before population collapse. We mapped the
      bifurcation diagram experimentally and found that the populations became more
      vulnerable to disturbance closer to the tipping point. Fluctuations of population
      density increased in size and duration near the tipping point, in agreement with
      the theory. Our results suggest that indicators of critical slowing down can
      provide advance warning of catastrophic thresholds and loss of resilience in a
      variety of dynamical systems.

PMID- 22654062
TI  - Restoring voluntary control of locomotion after paralyzing spinal cord injury.
AB  - Half of human spinal cord injuries lead to chronic paralysis. Here, we introduce
      an electrochemical neuroprosthesis and a robotic postural interface designed to
      encourage supraspinally mediated movements in rats with paralyzing lesions.
      Despite the interruption of direct supraspinal pathways, the cortex regained the
      capacity to transform contextual information into task-specific commands to
      execute refined locomotion. This recovery relied on the extensive remodeling of
      cortical projections, including the formation of brainstem and intraspinal relays
      that restored qualitative control over electrochemically enabled lumbosacral
      circuitries. Automated treadmill-restricted training, which did not engage
      cortical neurons, failed to promote translesional plasticity and recovery. By
      encouraging active participation under functional states, our training paradigm
      triggered a cortex-dependent recovery that may improve function after similar
      injuries in humans.

PMID- 22654064
TI  - Integrated care: a story of hard won success.

PMID- 22654063
TI  - Carbapenem antibiotics for serious infections.

PMID- 22654065
TI  - A third of cardiac arrests in hospital could have been prevented, finds inquiry.

PMID- 22654066
TI  - People and planet: from vicious cycle to virtuous circle.

PMID- 22654067
TI  - Improving vascular health: are pills the answer?

PMID- 22654068
TI  - Down on the "pharm": do genetically modified plants hold the key to cheaper
      drugs?

PMID- 22654069
TI  - Army doctor who tried to resuscitate Iraqi man after soldier's beating faces GMC
      hearing.

PMID- 22654070
TI  - Psychoanalysis can seriously damage your health.

PMID- 22654071
TI  - Private company that took over failing NHS hospital seeks {pound}47.5m to prevent
      insolvency.

PMID- 22654072
TI  - Experts call for more safe sex education as gonorrhoea cases rise by a quarter in
      England.

PMID- 22654073
TI  - Prepregnancy care.

PMID- 22654074
TI  - Northern Ireland signs deal for electronic patient records after successful
      pilot.

PMID- 22654075
TI  - Appetite for patient safety in England falls behind that in the rest of the UK,
      conference hears.

PMID- 22654076
TI  - Watchdog inspects Cornish out of hours service after doctors complain.

PMID- 22654077
TI  - Critics call for "misleading" consultation on shared decision making to be
      withdrawn.

PMID- 22654078
TI  - Management of work-related asthma: guidelines and challenges.

PMID- 22654079
TI  - A trans-disciplinary overview of case reports of thunderstorm-related asthma
      outbreaks and relapse.

PMID- 22654080
TI  - Contribution of host factors and workplace exposure to the outcome of
      occupational asthma.
AB  - The outcome of occupational asthma after diagnosis is often poor. The
      identification of factors associated with a worse outcome may help in the
      management of the disease, determining its prognosis and assessing the permanent
      impairment attributable to occupational exposure. The aim of this systematic
      review was to provide the available evidence from the medical literature to
      answer the question: "What is the contribution of host factors and workplace
      exposure to the risk of a bad outcome of occupational asthma?" A systematic
      literature search was conducted in March 2010. We retrieved 177 abstracts. Of
      these, 67 were assessed as potentially relevant. After full text evaluation, 35
      articles that were actually relevant for the question were included in the
      analysis. The information obtained was sufficient to establish that older age,
      high-molecular-weight agents, impaired lung function and longer duration of
      exposure to the offending agent at the time of diagnosis had a negative role on
      the outcome of occupational asthma. Atopy and smoking at diagnosis did not seem
      to influence the outcome of occupational asthma. A limited number of studies
      considered sex and the pattern of asthmatic reaction on specific inhalation
      challenge and their findings were contradictory.

PMID- 22654081
TI  - What is the optimal management option for occupational asthma?
AB  - The optimal management of occupational asthma remains uncertain in clinical
      practice. The aim of this review was to analyse the published information
      pertaining to the management of occupational asthma in order to produce evidence
      based statements and recommendations. A systematic literature search was
      conducted up to March 2010 to identify original studies addressing the following
      different treatment options: 1) persistence of exposure; 2) pharmacological
      treatment; 3) complete avoidance of exposure; 4) reduction of exposure; and 5)
      the use of personal protective equipment. After full text evaluation of 83
      potentially relevant articles, 52 studies were retained for analysis. The
      conclusions from this systematic review are limited by the methodological
      weaknesses of most published studies. Critical analysis of available evidence
      indicates that: 1) persistent exposure to the causal agent is more likely to
      result in asthma worsening than complete avoidance; 2) there is insufficient
      evidence to determine whether pharmacological treatment can alter the course of
      asthma in subjects who remain exposed; 3) avoidance of exposure leads to recovery
      of asthma in less than one-third of affected workers; 4) reduction of exposure
      seems to be less beneficial than complete avoidance of exposure; and 5) personal
      respiratory equipment does not provide complete protection.

PMID- 22654082
TI  - What are the benefits of medical screening and surveillance?
AB  - Pre-employment examination is considered to be an important practice and is
      commonly performed in several countries within the European Union. The benefits
      of medical surveillance programmes are not generally accepted and their structure
      is often inconsistent. The aim of this review was to evaluate, on the basis of
      the available literature, the usefulness of medical screening and surveillance.
      MEDLINE was searched from its inception up to March 2010. Retrieved literature
      was evaluated in a peer-review process and relevant data was collected following
      a systematic extraction schema. Pre-placement screening identifies subjects who
      are at an increased risk for developing work-related allergic disease, but pre
      employment screening is too low to be used as exclusion criteria. Medical
      surveillance programmes can identify workers who have, or who are developing,
      work-related asthma. These programmes can also be used to avoid worsening of
      symptoms by implementing preventive measures. A combination of different tools
      within the surveillance programme, adjusted for the risk of the individual
      worker, improves the predictive value. Medical surveillance programmes provide
      medical as well as socioeconomic benefits. However, pre-employment screening
      cannot be used to exclude workers. They may act as a starting point for
      surveillance strategies. A stratified approach can increase the effectiveness and
      reduce the costs for such programmes.

PMID- 22654083
TI  - Primary prevention: exposure reduction, skin exposure and respiratory protection.
AB  - Interventions for the primary prevention of occupational asthma have been
      reported in the medical literature, understanding the effectiveness of these
      efforts could help future interventions. The aim of our study was to evaluate the
      existing knowledge regarding the impact of controlling work exposure on the
      prevention of occupational asthma. We conducted systematic literature searches
      through April 2010 to examine if control of workplace exposures is effective for
      primary prevention of sensitisation and occupational asthma. The literature
      search for primary prevention of occupational asthma yielded 29 studies.
      Assessment of the available information led to the following conclusions and
      recommendations concerning primary prevention of occupational asthma. Exposure
      elimination is the strongest and preferred primary preventive approach to reduce
      the burden of occupational asthma. If elimination is not possible, exposure
      reduction is the second best option for primary prevention of occupational
      asthma. The evidence for the effectiveness of respirators in preventing
      occupational asthma is limited, and other options higher in the list of controls
      for occupational exposures, notably eliminating or minimising exposures at the
      source or in the environment, should be used preferentially. There is strong
      evidence to recommend not using powdered allergen-rich natural rubber latex
      gloves. There is weak evidence that suggests workers should minimise skin
      exposure to asthma-inducing agents.

PMID- 22654085
TI  - Idiopathic pulmonary fibrosis: recent milestones in disease management.

PMID- 22654084
TI  - The management of work-related asthma guidelines: a broader perspective.
AB  - The aim of the European Respiratory Society work-related asthma guidelines is to
      present the management and prevention options of work-related asthma and their
      effectiveness. Work-related asthma accounts for 5-25% of all adult asthma cases
      and is responsible for a significant socioeconomic burden. Several hundred
      occupational agents, mainly allergens but also irritants and substances with
      unknown pathological mechanisms, have been identified as causing work-related
      asthma. The essential message of these guidelines is that the management of work
      related asthma can be considerably optimised based on the present knowledge of
      causes, risk factors, pathomechanisms, and realistic and effective interventions.
      To reach this goal we urgently require greatly intensified primary preventive
      measures and improved case management. There is now a substantial body of
      evidence supporting the implementation of comprehensive medical surveillance
      programmes for workers at risk. Those workers who fail surveillance programmes
      need to be referred to a clinician who can confirm or exclude an occupational
      cause. Once work-related asthma is confirmed, a revised risk assessment in the
      workplace is needed to prevent further cases. These new guidelines confirm and
      extend already existing statements and recommendations. We hope that these
      guidelines will initiate the much-needed research that is required to fill the
      gaps in our knowledge and to initiate substantial improvements in preventative
      measures.

PMID- 22654086
TI  - An earlier and more confident diagnosis of idiopathic pulmonary fibrosis.
AB  - A diagnosis of idiopathic pulmonary fibrosis (IPF) has serious implications for
      the affected individuals, who have a 50% likelihood of dying within 2-3 yrs, an
      outcome which is worse than many cancers. A swift and accurate diagnosis is
      imperative, especially as commencing treatment at a relatively early disease
      stage may have the greatest impact on reducing disease progression. The 2011, IPF
      guidelines provide updated and simplified IPF diagnostic criteria that may
      facilitate making a more confident diagnosis. The key investigational tool is
      high-resolution computed tomography (HRCT). In the presence of the four classical
      features, that together accurately identify a usual interstitial pneumonia (UIP)
      pattern, a definitive diagnosis of IPF can be made. When HRCT honeycombing is
      absent, even in the presence of all other features including traction
      bronchiectasis, the guidelines provide no designation for this constellation of
      features that many clinicians and radiologists would regard as consistent with
      UIP. The diagnostic algorithm suggested by the 2011 guidelines emphasises the
      importance of multidisciplinary discussion between clinicians, radiologists and
      pathologists to improve diagnostic confidence. The course of disease in IPF is
      unpredictable, but the importance of an early diagnosis is clear, as individuals
      with less severe lung function abnormalities have a better prognosis.

PMID- 22654087
TI  - Assessing the treatment effect from multiple trials in idiopathic pulmonary
      fibrosis.
AB  - The magnitude of treatment effect can be assessed by a number of methods. One
      method of collectively analysing data is that used by the Cochrane Collaboration.
      Their systematic reviews identify, analyse and present research-based evidence in
      an accessible format. These reviews may contain meta-analyses combining data from
      multiple studies to provide robust evaluations of overall treatment effects. In
      2003, Cochrane reviews of data for treatment with corticosteroids in idiopathic
      pulmonary fibrosis (IPF) found no evidence supporting their use; similarly,
      reviews of immunomodulatory agents found very little evidence to support their
      use. A recent update of these Cochrane reviews failed to identify any evidence
      supporting the use of corticosteroids in IPF; however, a review of non-steroid
      agents in the treatment of IPF identified 15 clinical trials suitable for
      analysis. Two trials of interferon-gamma-1b were combined, and no treatment
      effect was observed in terms of survival. Two Japanese trials of treatment with
      pirfenidone were combined, and a positive effect of pirfenidone on pulmonary
      function decline was observed. Meta-analysis of three phase III studies suggested
      that pirfenidone significantly increased progression-free survival by 30%. The
      findings of this systematic review, although not presenting new original data,
      together with an acceptable safety profile, suggest that pirfenidone may have a
      role in IPF treatment.

PMID- 22654088
TI  - Unravelling the progressive pathophysiology of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a life-threatening condition, with a
      median survival of <3 yrs. The pathophysiology is not fully understood, but
      chronic injury of alveolar epithelial type II cells (AECII) is considered key. In
      IPF, disturbed folding and processing of surfactant proteins and impaired DNA
      repair may represent underlying reasons for maladaptive endoplasmic reticulum
      stress responses, increased reactive oxygen species production and/or DNA damage.
      Excessive AECII apoptosis occurs, leading to permanently perturbed epithelial
      homeostasis. The role of secondary hits also becomes evident. These may aggravate
      the disease and result in increased epithelial turnover, exhausting the
      regenerative capacity of progenitors and disturbing epithelial-mesenchymal
      interactions. Fibroblast proliferation, transdifferentiation and matrix
      deposition may be mediated through various mechanisms including epithelial
      mesenchymal transition, fibrocyte invasion or expansion of a local fibroblast
      population. Treatment modalities aiming to attenuate epithelial injury are
      currently in early pre-clinical development and may reach the clinical arena in
      only a few years. Meanwhile, novel drugs acting on highly activated fibroblasts
      such as pirfenidone, an anti-fibrotic drug authorised for IPF in the European
      Union, or BIBF 1120, a novel triple-kinase inhibitor (blocking vascular
      endothelial growth factor, platelet-derived growth factor and fibroblast growth
      factor) currently under clinical investigation, seem to attenuate the progression
      of IPF.

PMID- 22654089
TI  - Changing the idiopathic pulmonary fibrosis treatment approach and improving
      patient outcomes.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic disease, with no
      effective treatment and a median survival time of 2-5 yrs. The search for
      effective treatment has involved numerous clinical trials of investigational
      agents without significant success until 2011, when European approval was given
      for the first treatment for IPF, pirfenidone. Four key clinical trials supported
      the efficacy and tolerability of pirfenidone. In recently published results from
      two phase III randomised, double-blind, placebo-controlled, multinational trials
      evaluating pirfenidone (studies 004 and 006), patients with mild-to-moderate IPF
      were screened for eligibility using the following functional criteria: forced
      vital capacity (FVC) >=50% predicted; diffusing capacity of the lung for carbon
      monoxide >=35%; and 6-min walk test (6MWT) distance >=150 m. Only study 004 met
      the primary end-point of change in per cent predicted FVC at week 72 (p<0.001).
      Pooled analysis of primary end-point data from both studies also showed that
      pirfenidone significantly reduced the decline in per cent predicted FVC compared
      to placebo (p<0.005). Evidence of beneficial effects of pirfenidone treatment was
      also observed with regard to several secondary end-points, including progression
      free survival time, categorical FVC change, and mean change from baseline to week
      72 in 6MWT distance. Pirfenidone was generally well tolerated, with the most
      common side-effects being gastrointestinal discomfort and photosensitivity. The
      pooled study results, coupled with recent data regarding the prognostic
      significance of changes in FVC and 6MWT, provide further evidence of a clinically
      meaningful treatment benefit with pirfenidone in patients with IPF.

PMID- 22654090
TI  - Hypersensitivity pneumonitis due to isocyanate exposure in an airbag "welder".

PMID- 22654091
TI  - A before and after study on personality assessment in adolescents exposed to the
      2009 earthquake in L'Aquila, Italy: influence of sports practice.
AB  - OBJECTIVE: To assess and estimate the personality changes that occurred before
      and after the 2009 earthquake in L'Aquila and to model the ways that the
      earthquake affected adolescents according to gender and sport practice. The
      consequences of earthquakes on psychological health are long lasting for portions
      of the population, depending on age, gender, social conditions and individual
      experiences. Sports activities are considered a factor with which to test the
      overall earthquake impact on individual and social psychological changes in
      adolescents. DESIGN: Before and after design. SETTING: Population-based study
      conducted in L'Aquila, Italy, before and after the 2009 earthquake. PARTICIPANTS:
      Before the earthquake, a random sample of 179 adolescent subjects who either
      practised or did not practise sports (71 vs 108, respectively). After the
      earthquake, of the original 179 subjects, 149 were assessed a second time.
      PRIMARY OUTCOME MEASURE: Minnesota Multiphasic Personality Inventory-Adolescents
      (MMPI-A) questionnaire scores, in a supervised environment. RESULTS: An
      unbalanced split plot design, at a 0.05 significance level, was carried out using
      a linear mixed model with quake, sex and sports practice as predictive factors.
      Although the overall scores indicated no deviant behaviours in the adolescents
      tested, changes were detected in many individual content scale scores, including
      depression (A-dep score mean +/- SEM: before quake =47.54+/-0.73; after quake
      =52.67+/-0.86) and social discomfort (A-sod score mean +/- SEM: before quake
      =49.91+/-0.65; after quake =51.72+/-0.81). The MMPI-A profiles show different
      impacts of the earthquake on adolescents according to gender and sport practice.
      CONCLUSIONS: The differences detected in MMPI-A scores raise issues about social
      policies required to address the psychological changes in adolescents. The
      current study supports the idea that sport should be considered part of a coping
      strategy to assist adolescents in dealing with the psychological effects of the
      earthquakes on their personalities.

PMID- 22654093
TI  - The best of the UK? A report on the value and future of UK databases in the
      health and social care fields: a systematic map protocol.
AB  - INTRODUCTION: This protocol covers the first part of a two-part project funded by
      the Health Libraries Group and the University Health and Medical Librarians
      Group. It details the proposed methodology for a systematic map of the literature
      relating to UK bibliographic databases in the fields of health and social care.
      The aim of this mapping exercise is to consider ways in which UK bibliographic
      databases are described, considered and discussed in the published and
      unpublished literature. In doing so, we hope to gain a clearer sense of the ways
      in which UK bibliographic databases are used and viewed by the research
      community. It also enables the identification of any gaps in the literature for
      further research and discussion. This topic is important because UK databases are
      generally underused by researchers in the UK context and some databases are at
      risk of closure. A lack of access to UK databases means that researchers may miss
      relevant UK evidence when identifying an evidence base. METHOD: Systematic Map.
      ANALYSIS: The authors will present a narrative description of the literature
      relating to UK bibliographic databases in the fields of health and social care.
      They will use tables to present descriptive information about the literature (eg,
      frequency tables) and use cross-tabulations to demonstrate intersecting themes.
      Separately, guidance on how to use the resources (eg, areas of unique content,
      updating frequencies, unique truncation symbols) will be sought from stakeholders
      and reported alongside the report narrative as a guide to usage.

PMID- 22654092
TI  - Too complex and time-consuming to fit in! Physicians' experiences of elderly
      patients and their participation in medical decision making: a grounded theory
      study.
AB  - OBJECTIVE: To explore physicians' thoughts and considerations of participation in
      medical decision making by hospitalised elderly patients. DESIGN: A qualitative
      study using focus group interviews with physicians interpreted with grounded
      theory and completed with a questionnaire. SETTING AND PARTICIPANTS: The setting
      was three different hospitals in two counties in Sweden. Five focus groups were
      conducted with physicians (n=30) in medical departments, with experience of care
      of elderly patients. RESULTS: Physicians expressed frustration at not being able
      to give good care to elderly patients with multimorbidity, including letting them
      participate in medical decision making. Two main categories were found: 'being
      challenged' by this patient group and 'being a small part of the healthcare
      production machine'. Both categories were explained by the core category 'lacking
      in time'. The reasons for the feeling of 'being challenged' were explained by the
      subcategories 'having a feeling of incompetence', 'having to take relatives into
      consideration' and 'having to take cognitive decline into account'. The reasons
      for the feeling of 'being a small part of the healthcare production machine' were
      explained by the subcategories 'at the mercy of routines' and 'inadequate
      remuneration system', both of which do not favour elderly patients with
      multimorbidity. CONCLUSIONS: Physicians find that elderly patients with
      multimorbidity lead to frustration by giving them a feeling of professional
      inadequacy, as they are unable to prioritise this common and rapidly growing
      patient group and enable them to participate in medical decision making. The
      reason for this feeling is explained by lack of time, competence, holistic view,
      appropriate routines and proper remuneration systems for treating these patients.

PMID- 22654094
TI  - Minimal coronary artery damage by myocardial electroporation ablation.
AB  - AIMS: Radiofrequency catheter ablation is a successful treatment for cardiac
      arrhythmias, but may lead to major complications such as permanent coronary
      damage. Irreversible electroporation (IRE) is a new non-thermal ablation
      modality, but its effect on coronary arteries is still unknown. METHODS AND
      RESULTS: In a porcine model, epicardial IRE lesions were created at the base of
      the left ventricle in four hearts (group A) and directly on the left anterior
      descending artery (LAD) in five hearts (group B). After 3 weeks, coronary
      arteries inside IRE lesions and in apparently undamaged myocardium next to the
      lesions were (immuno-)histologically studied. Two untreated hearts served as
      controls. Coronary damage was defined as intimal hyperplasia. Left anterior
      descending artery angiograms were obtained before ablation, directly after
      ablation, and before termination in group B. In group A, 103 arterial branches
      were studied. Of these, 5 of 56 arterial branches inside lesions and 1 of 47
      outside lesions showed intimal hyperplasia, but all had <50% area stenosis.
      Targeted LADs (group B) did not reveal intimal hyperplasia and angiograms showed
      no signs of stenosis. Expression of connective tissue growth factor was observed
      in the scar tissue, but not in the fibrotic tissue directly around the arteries,
      confirming that the arteries are indeed spared from tissue damage and
      remodelling. CONCLUSION: Coronary arteries remain free of clinically relevant
      damage 3 weeks after epicardial IRE ablation, even amid very large myocardial
      lesions. This suggests that IRE ablation can be applied safely near or even on
      coronary arteries. With IRE ablation, arterial blood flow does not appear to
      affect lesion formation.

PMID- 22654095
TI  - So you implanted an implantable cardioverter defibrillator, now what to do with
      it?

PMID- 22654096
TI  - Prognostic value of left atrial expansion index and exercise-induced change in
      atrial natriuretic peptide as long-term predictors of atrial fibrillation
      recurrence.
AB  - AIMS: We propose to assess the value of exercise-induced change in N-terminal-pro
      atrial natriuretic peptide (NT-proANP) and left atrial expansion index (LAEI) in
      predicting AFR after cardioversion and their effect on AF-free survival. METHODS
      AND RESULTS: Fifty-five patients with persistent AF of <18 months duration
      needing cardioversion were recruited for the study. Fifty-four patients were
      successfully cardioverted. At 3 months 28/54 (51%) were in SR and at 12 months
      21/53 (39%). On multivariate analysis, only exercise-induced change in NT-proANP
      and LAEI were found to be predictive of AFR up to 12 months post-cardioversion
      and had an effect on AF-free survival. N-terminal-pro brain natriuretic peptide
      was elevated in all persistent AF patients but did not predict recurrent AF.
      CONCLUSIONS: Left atrial expansion index and exercise-induced atrial natriuretic
      peptide change show promise as predictors of AFR after cardioversion. These
      predictors may identify patients at an early stage in their disease with intact
      neurohumoral feedback systems and less advanced atrial remodelling. Further
      studies are required to confirm these findings.

PMID- 22654097
TI  - Assessing fitness, predicting outcome, and the missing axis.
AB  - Summary This article discusses how to estimate the risk of postoperative death,
      an outcome that affects an important minority of patients in the month(s) after
      scheduled surgery. In addition, it reflects on our inability to characterize the
      effects of surgery on quality of life. This outcome is of primary concern to the
      much more numerous survivors but is absent from all graphs of postoperative
      survival: it is the missing axis. The calculations discussed in the article are
      available online at https://sites.google.com/site/informrisk/.

PMID- 22654098
TI  - Measuring and recording outcome.
AB  - Achieving good health outcomes for patients is the fundamental purpose of
      healthcare. What really matters to patients is the outcome of an intervention and
      the effect it will have on their wellbeing and life expectancy. After media
      coverage, and public enquiry into high mortality rates for paediatric cardiac
      surgery at the Bristol Royal Infirmary during the early 1990s, mortality rates
      for paediatric cardiac surgical procedures decreased dramatically both in Bristol
      and nationally. There can be little doubt that one of the prime 'drivers for
      change' was the placement of outcome data into the public domain. After events in
      Bristol, the Society for Cardiothoracic Surgery in Britain and Ireland (SCTS) has
      taken the lead in measuring and publishing clinical outcome data. It has also
      discussed how outcome data could be used to assess an individual's clinical
      performance and how, in the future, this might be linked to continuing
      professional development, appraisal, and revalidation. Measuring quality and
      outcome in healthcare is complex. Ideal outcome measures should be specific,
      sensitive, reliable, responsive, validated, timely, and easy to measure.
      Monitoring of outcomes can be 'process' orientated or 'clinically' orientated.
      The 2010 National Health Service (NHS) White Paper aimed for an NHS which 'moves
      away from centrally driven process targets and focuses on delivering outcomes
      which matter to people'. Measuring outcome in anaesthesia is problematic. There
      are issues around clinical coding, risk adjustment, the influence of clinical
      teamworking, and environmental factors. The National Institute of Academic
      Anaesthesia (NIAA) has identified that the description of clinical practice in
      anaesthesia and perioperative medicine is currently limited by a lack of valid,
      reliable quality measures. The NIAA suggests that there is a requirement for
      further research into identifying the anaesthetic outcome indicators which are
      most relevant to patients, and then benchmarking the performance of anaesthetic
      departments and anaesthetists.

PMID- 22654099
TI  - The Salmonella type III secretion system inner rod protein PrgJ is partially
      folded.
AB  - The type III secretion system (T3SS) is essential in the pathogenesis of many
      bacteria. The inner rod is important in the assembly of the T3SS needle complex.
      However, the atomic structure of the inner rod protein is currently unknown.
      Based on computational methods, others have suggested that the Salmonella inner
      rod protein PrgJ is highly helical, forming a folded 3 helix structure. Here we
      show by CD and NMR spectroscopy that the monomeric form of PrgJ lacks a tertiary
      structure, and the only well-structured part of PrgJ is a short alpha-helix at
      the C-terminal region from residues 65-82. Disruption of this helix by glycine or
      proline mutation resulted in defective assembly of the needle complex, rendering
      bacteria incapable of secreting effector proteins. Likewise, CD and NMR data for
      the Shigella inner rod protein MxiI indicate this protein lacks a tertiary
      structure as well. Our results reveal that the monomeric forms of the T3SS inner
      rod proteins are partially folded.

PMID- 22654100
TI  - Identification of a novel Francisella tularensis factor required for
      intramacrophage survival and subversion of innate immune response.
AB  - Francisella tularensis, the causative agent of tularemia, is one of the deadliest
      agents of biological warfare and bioterrorism. Extremely high virulence of this
      bacterium is associated with its ability to dampen or subvert host innate immune
      response. The objectives of this study were to identify factors and understand
      the mechanisms of host innate immune evasion by F. tularensis. We identified and
      explored the pathogenic role of a mutant interrupted at gene locus FTL_0325,
      which encodes an OmpA-like protein. Our results establish a pathogenic role of
      FTL_0325 and its ortholog FTT0831c in the virulent F. tularensis SchuS4 strain in
      intramacrophage survival and suppression of proinflammatory cytokine responses.
      This study provides mechanistic evidence that the suppressive effects on innate
      immune responses are due specifically to these proteins and that FTL_0325 and
      FTT0831c mediate immune subversion by interfering with NF-kappaB signaling.
      Furthermore, FTT0831c inhibits NF-kappaB activity primarily by preventing the
      nuclear translocation of p65 subunit. Collectively, this study reports a novel F.
      tularensis factor that is required for innate immune subversion caused by this
      deadly bacterium.

PMID- 22654101
TI  - Prostanoid receptor 2 signaling protects T helper 2 cells from BALB/c mice
      against activation-induced cell death.
AB  - T helper 2 (Th2) cells play a central role in the progression of many diseases
      such as allergic airway inflammation, autoimmune diseases, and infections caused
      by intracellular pathogens. Consequently, animals such as BALB/c mice, which
      exhibit a propensity for generating Th2 responses, are susceptible to allergic
      airway inflammation, type-II autoimmune diseases, and various infections induced
      by intracellular pathogens, namely, Leishmania. In contrast, C3H/OuJ mice have a
      tendency for generating T helper 1 (Th1) responses and show resistance to these
      diseases. Here, we show that prostaglandin endoperoxide E(2) selectively inhibits
      activation-induced cell death of Th2 cells by signaling through its receptor E
      prostanoid receptor 2 (EP2). Consequently, Th2 cells derived from BALB/c mice
      expressed very high levels of EP2. On the other hand, Th2 cells derived from
      C3H/OuJ mice expressed very low levels of EP2, which failed to support the
      survival of Th2 cells. Furthermore, we found that this effect of EP2 on Th2 cells
      from BALB/c mice was executed by a granzyme B-mediated mechanism. EP2 belongs to
      a group of G-protein-coupled receptors that are amenable to therapeutic
      targeting. Our findings therefore identify EP2 as a promising target for small
      molecule-directed immunomodulation.

PMID- 22654102
TI  - Glioblastoma-derived tumor cells induce vasculogenic mimicry through Flk-1
      protein activation.
AB  - Glioblastoma (GBM) is extremely aggressive and essentially incurable. Its
      malignancy is characterized by vigorous microvascular proliferations. Recent
      evidence has shown that tumor cells display the ability to drive blood-perfused
      vasculogenic mimicry (VM), an alternative microvascular circulation independent
      of endothelial cell angiogenesis. However, molecular mechanisms underlying this
      vascular pathogenesis are poorly understood. Here, we found that vascular
      channels of VM in GBM were composed of mural-like tumor cells that strongly
      express VEGF receptor 2 (Flk-1). To explore a potential role of Flk-1 in the
      vasculogenesis, we investigated two glioblastoma cell lines U87 and GSDC, both of
      which express Flk-1 and exhibit a vascular phenotype on Matrigel. Treatment of
      both cell lines with either Flk-1 gene knockdown or Flk-1 kinase inhibitor SU1498
      abrogated Flk-1 activity and impaired vascular function. Furthermore, inhibition
      of Flk-1 activity suppressed intracellular signaling cascades, including focal
      adhesion kinase and mitogen-activated protein kinase ERK1/2. In contrast,
      blockade of VEGF activity by the neutralizing antibody Bevacizumab failed to
      recapitulate the impact of SU1498, suggesting that Flk-1-mediated VM is
      independent of VEGF. Xenotransplantation of SCID/Beige mice with U87 cells and
      GSDCs gave rise to tumors harboring robust mural cell-associated vascular
      channels. Flk-1 shRNA restrained VM in tumors and subsequently inhibited tumor
      development. Collectively, all the data demonstrate a central role of Flk-1 in
      the formation of VM in GBM. This study has shed light on molecular mechanisms
      mediating tumor aggressiveness and also provided a therapeutic target for patient
      treatment.

PMID- 22654103
TI  - Cdk5 levels oscillate during the neuronal cell cycle: Cdh1 ubiquitination
      triggers proteosome-dependent degradation during S-phase.
AB  - When cell cycle re-activation occurs in post-mitotic neurons it places them at
      increased risk for death. The cell cycle/cell death association has been reported
      in many neurodegenerative diseases including Alzheimer disease (AD), yet the
      mechanisms by which a normal neuron suppresses the cycle remain largely unknown.
      Recently, our laboratory has shown that Cdk5 (cyclin-dependent kinase 5) is a key
      player in this protective function. When a neuron is under stress, Cdk5 is
      transported to the cytoplasm; this eliminates its cell cycle suppression activity
      and the neuron re-enters S-phase. In the current study we show that a similar
      principle applies during a normal cell cycle. When a neuronal cell enters S
      phase, Cdk5 is transported to the cytoplasm where it is ubiquitinated by the E3
      ligase APC-Cdh1. Ubiquitinated Cdk5 is then rapidly degraded by the proteasome.
      The ubiquitination site of Cdk5 appears to be in the p35 binding area; in the
      presence of high levels of p35, the ubiquitination of Cdk5 was blocked, and the
      degradation in S phase was attenuated. The data suggest an unsuspected role for
      Cdk5 during the progression of a normal cell cycle and offer new pharmaceutical
      targets for regulating neuronal cell cycling and cell death.

PMID- 22654104
TI  - Methionine oxidation perturbs the structural core of the prion protein and
      suggests a generic misfolding pathway.
AB  - Oxidative stress and misfolding of the prion protein (PrP(C)) are fundamental to
      prion diseases. We have therefore probed the effect of oxidation on the structure
      and stability of PrP(C). Urea unfolding studies indicate that H(2)O(2) oxidation
      reduces the thermodynamic stability of PrP(C) by as much as 9 kJ/mol. (1)H-(15)N
      NMR studies indicate methionine oxidation perturbs key hydrophobic residues on
      one face of helix-C as follows: Met-205, Val-209, and Met-212 together with
      residues Val-160 and Tyr-156. These hydrophobic residues pack together and form
      the structured core of the protein, stabilizing its ternary structure. Copper
      catalyzed oxidation of PrP(C) causes a more significant alteration of the
      structure, generating a monomeric molten globule species that retains its native
      helical content. Further copper-catalyzed oxidation promotes extended beta-strand
      structures that lack a cooperative fold. This transition from the helical molten
      globule to beta-conformation has striking similarities to a misfolding
      intermediate generated at low pH. PrP may therefore share a generic misfolding
      pathway to amyloid fibers, irrespective of the conditions promoting misfolding.
      Our observations support the hypothesis that oxidation of PrP destabilizes the
      native fold of PrP(C), facilitating the transition to PrP(Sc). This study gives a
      structural and thermodynamic explanation for the high levels of oxidized
      methionine in scrapie isolates.

PMID- 22654105
TI  - Nuclear factor-kappaB regulates betaAPP and beta- and gamma-secretases
      differently at physiological and supraphysiological Abeta concentrations.
AB  - Anatomical lesions in Alzheimer disease-affected brains mainly consist of senile
      plaques, inflammation stigmata, and oxidative stress. The nuclear factor-kappaB
      (NF-kappaB) is a stress-activated transcription factor that is activated around
      senile plaques. We have assessed whether NF-kappaB could be differentially
      regulated at physiological or supraphysiological levels of amyloid beta (Abeta)
      peptides. Under these experimental conditions, we delineated the putative NF
      kappaB-dependent modulation of all cellular participants in Abeta production,
      namely its precursor betaAPP (beta-amyloid precursor protein) and the beta- and
      gamma-secretases, the two enzymatic machines involved in Abeta genesis. Under
      physiological conditions, NF-kappaB lowers the transcriptional activity of the
      promoters of betaAPP, beta-secretase (beta-site APP-cleaving enzyme 1, BACE1),
      and of the four protein components (Aph-1, Pen-2, nicastrin, presenilin-1, or
      presenilin-2) of the gamma-secretase in HEK293 cells. This was accompanied by a
      reduction of both protein levels and enzymatic activities, thereby ultimately
      yielding lower amounts of Abeta and AICD (APP intracellular domain). In stably
      transfected Swedish betaAPP-expressing HEK293 cells triggering supraphysiological
      concentrations of Abeta peptides, NF-kappaB activates the transcription of
      betaAPP, BACE1, and some of the gamma-secretase members and increases protein
      expression and enzymatic activities, resulting in enhanced Abeta production. Our
      pharmacological approach using distinct NF-kappaB kinase modulators indicates
      that both NF-kappaB canonical and alternative pathways are involved in the
      control of Abeta production. Overall, our data demonstrate that under
      physiological conditions, NF-kappaB triggers a repressive effect on Abeta
      production that contributes to maintaining its homeostasis, while NF-kappaB
      participates in a degenerative cycle where Abeta would feed its own production
      under pathological conditions.

PMID- 22654106
TI  - Primary mesenchymal stem and progenitor cells from bone marrow lack expression of
      CD44 protein.
AB  - Despite significant progress in our understanding of mesenchymal stem cell (MSC)
      biology during recent years, much of the information is based on experiments
      using in vitro culture-selected stromal progenitor cells. Therefore, the natural
      cellular identity of MSCs remains poorly defined. Numerous studies have reported
      that CD44 expression is one of the characteristics of MSCs in both humans and
      mice; however, we here have prospectively isolated bone marrow stromal cell
      subsets from both human and mouse bone marrow by flow cytometry and characterized
      them by gene expression analysis and function assays. Our data provide functional
      and molecular evidence suggesting that primary mesenchymal stem and progenitor
      cells of bone marrow reside in the CD44(-) cell fraction in both mice and humans.
      The finding that these CD44(-) cells acquire CD44 expression after in vitro
      culture provides an explanation for the previous misconceptions concerning CD44
      expression on MSCs. In addition, the other previous reported MSC markers,
      including CD73, CD146, CD271, and CD106/VCAM1, are also differentially expressed
      on those two cell types. Our microarray data revealed a distinct gene expression
      profile of the freshly isolated CD44(-) cells and the cultured MSCs generated
      from these cells. Thus, we conclude that bone marrow MSCs physiologically lack
      expression of CD44, highlighting the natural phenotype of MSCs and opening new
      possibilities to prospectively isolate MSCs from the bone marrow.

PMID- 22654107
TI  - L-xylo-3-hexulose reductase is the missing link in the oxidoreductive pathway for
      D-galactose catabolism in filamentous fungi.
AB  - In addition to the well established Leloir pathway for the catabolism of d
      galactose in fungi, the oxidoreductive pathway has been recently identified. In
      this oxidoreductive pathway, D-galactose is converted via a series of NADPH
      dependent reductions and NAD(+)-dependent oxidations into D-fructose. The pathway
      intermediates include galactitol, L-xylo-3-hexulose, and d-sorbitol. This study
      identified the missing link in the pathway, the L-xylo-3-hexulose reductase that
      catalyzes the conversion of L-xylo-3-hexulose to D-sorbitol. In Trichoderma
      reesei (Hypocrea jecorina) and Aspergillus niger, we identified the genes lxr4
      and xhrA, respectively, that encode the l-xylo-3-hexulose reductases. The
      deletion of these genes resulted in no growth on galactitol and in reduced growth
      on D-galactose. The LXR4 was heterologously expressed, and the purified protein
      showed high specificity for L-xylo-3-hexulose with a K(m) = 2.0 +/- 0.5 mm and a
      V(max) = 5.5 +/- 1.0 units/mg. We also confirmed that the product of the LXR4
      reaction is D-sorbitol.

PMID- 22654108
TI  - A regulatory feedback loop between Ca2+/calmodulin-dependent protein kinase
      kinase 2 (CaMKK2) and the androgen receptor in prostate cancer progression.
AB  - The androgen receptor (AR) plays a critical role in prostate cancer (PCa)
      progression, however, the molecular mechanisms by which the AR regulates cell
      proliferation in androgen-dependent and castration-resistant PCa are incompletely
      understood. We report that Ca(2+)/calmodulin-dependent kinase kinase 2 (CaMKK2)
      expression increases and becomes nuclear or perinuclear in advanced PCa. In the
      TRAMP (transgenic adenocarcinoma of mouse prostate) model of PCa, CaMKK2
      expression increases with PCa progression with many cells exhibiting nuclear
      staining. CaMKK2 expression is higher in human castration-resistant tumor
      xenografts compared with androgen-responsive xenografts and is markedly higher in
      the AR-expressing, tumorigenic cell line LNCaP compared with cell lines that are
      AR-nonexpressing and/or nontumorigenic. In LNCaP cells, dihydrotestosterone
      induced CaMKK2 mRNA and protein expression and translocation of CaMKK2 to the
      nucleus. Conversely, androgen withdrawal suppressed CaMKK2 expression. Knockdown
      of CaMKK2 expression by RNAi reduced LNCaP cell proliferation and increased
      percentages of cells in G(1) phase, whereas correspondingly reducing percentages
      in S phase, of the cell cycle. CaMKK2 knockdown reduced expression of the AR
      target gene prostate-specific antigen at both mRNA and protein levels, AR
      transcriptional activity driven by androgen responsive elements from the prostate
      specific probasin gene promoter and levels of the AR-regulated cell cycle
      proteins, cyclin D1 and hyperphosphorylated Rb. Our results suggest that in PCa
      progression, CaMKK2 and the AR are in a feedback loop in which CaMKK2 is induced
      by the AR to maintain AR activity, AR-dependent cell cycle control, and continued
      cell proliferation.

PMID- 22654109
TI  - Heparan sulfate dissociates serum amyloid A (SAA) from acute-phase high-density
      lipoprotein, promoting SAA aggregation.
AB  - Inflammation-related (AA) amyloidosis is a severe clinical disorder characterized
      by the systemic deposition of the acute-phase reactant serum amyloid A (SAA). SAA
      is normally associated with the high-density lipoprotein (HDL) fraction in
      plasma, but under yet unclear circumstances, the apolipoprotein is converted into
      amyloid fibrils. AA amyloid and heparan sulfate (HS) display an intimate
      relationship in situ, suggesting a role for HS in the pathogenic process. This
      study reports that HS dissociates SAA from HDLs isolated from inflamed mouse
      plasma. Application of surface plasmon resonance spectroscopy and molecular
      modeling suggests that HS simultaneously binds to two apolipoproteins of HDL, SAA
      and ApoA-I, and thereby induce SAA dissociation. The activity requires a minimum
      chain length of 12-14 sugar units, proposing an explanation to previous findings
      that short HS fragments preclude AA amyloidosis. The results address the initial
      events in the pathogenesis of AA amyloidosis.

PMID- 22654110
TI  - Hyaluronan expressed by the hematopoietic microenvironment is required for bone
      marrow hematopoiesis.
AB  - The contribution of hyaluronan (HA) to the regulatory network of the
      hematopoietic microenvironment was studied using knock-out mice of three
      hyaluronan synthase genes (Has1, Has2, and Has3). The number of hematopoietic
      progenitors was decreased in bone marrow and increased in extramedullary sites of
      Prx1-Cre;Has2(flox/flox);Has1(-/-);Has3(-/-) triple knock-out (tKO) mice as
      compared with wild type (WT) and Has1(-/-);Has3(-/-) double knock-out (dKO) mice.
      In line with this observation, decreased hematopoietic activity was observed in
      long term bone marrow cultures (LTBMC) from tKO mice, whereas the formation of
      the adherent layer and generation of hematopoietic cells in WT and dKO cultures
      was not different. 4-Methylumbelliferone (4MU) was used to pharmacologically
      inhibit the production of HA in LTBMC. Treatment with 4MU inhibited HA synthesis,
      decreased expression of HAS2 and HAS3, and eliminated hematopoiesis in LTBMC, and
      this effect was alleviated by the addition of exogenous HA. Exogenous HA also
      augmented the cell motility in LTBMC, which correlated with the HA-stimulated
      production of chemokines and growth factors. Conditioned media from HA-induced
      LTBMC enhanced the chemotaxis of hematopoietic stem/progenitor cells (HSPC) in
      response to SDF-1. Exposure of endothelial cells to 4MU decreased their ability
      to support HSPC rolling and adhesion. In addition, migration of transplanted HSPC
      into the marrow of 4MU-pretreated mice was lower than in untreated mice.
      Collectively, the results suggest that HA depletion reduces the ability of the
      microenvironment to support HSPC, and confirm a role for HA as a necessary
      regulatory element in the structure of the hematopoietic microenvironment.

PMID- 22654111
TI  - Elevated carbon dioxide blunts mammalian cAMP signaling dependent on inositol
      1,4,5-triphosphate receptor-mediated Ca2+ release.
AB  - Elevated CO(2) is generally detrimental to animal cells, suggesting an
      interaction with core processes in cell biology. We demonstrate that elevated
      CO(2) blunts G protein-activated cAMP signaling. The effect of CO(2) is
      independent of changes in intracellular and extracellular pH, independent of the
      mechanism used to activate the cAMP signaling pathway, and is independent of cell
      context. A combination of pharmacological and genetic tools demonstrated that the
      effect of elevated CO(2) on cAMP levels required the activity of the IP(3)
      receptor. Consistent with these findings, CO(2) caused an increase in steady
      state cytoplasmic Ca(2+) concentrations not observed in the absence of the IP(3)
      receptor or under nonspecific acidotic conditions. We examined the well
      characterized cAMP-dependent inhibition of the isoform 3 Na(+)/H(+) antiporter
      (NHE3) to demonstrate a functional relevance for CO(2)-mediated reductions in
      cellular cAMP. Consistent with the cellular biochemistry, elevated CO(2)
      abrogated the inhibitory effect of cAMP on NHE3 function via an IP(3) receptor
      dependent mechanism.

PMID- 22654112
TI  - The ciliary protein nephrocystin-4 translocates the canonical Wnt regulator Jade
      1 to the nucleus to negatively regulate beta-catenin signaling.
AB  - Nephronophthisis (NPH) is an autosomal-recessive cystic kidney disease and
      represents the most common genetic cause for end-stage renal disease in children
      and adolescents. It can be caused by the mutation of genes encoding for the
      nephrocystin proteins (NPHPs). All NPHPs localize to primary cilia, classifying
      this disease as a "ciliopathy." The primary cilium is a critical regulator of
      several cell signaling pathways. Cystogenesis in the kidney is thought to involve
      overactivation of canonical Wnt signaling, which is negatively regulated by the
      primary cilium and several NPH proteins, although the mechanism remains unclear.
      Jade-1 has recently been identified as a novel ubiquitin ligase targeting the
      canonical Wnt downstream effector beta-catenin for proteasomal degradation. Here,
      we identify Jade-1 as a novel component of the NPHP protein complex. Jade-1
      colocalizes with NPHP1 at the transition zone of primary cilia and interacts with
      NPHP4. Furthermore, NPHP4 stabilizes protein levels of Jade-1 and promotes the
      translocation of Jade-1 to the nucleus. Finally, NPHP4 and Jade-1 additively
      inhibit canonical Wnt signaling, and this genetic interaction is conserved in
      zebrafish. The stabilization and nuclear translocation of Jade-1 by NPHP4
      enhances the ability of Jade-1 to negatively regulate canonical Wnt signaling.
      Loss of this repressor function in nephronophthisis might be an important factor
      promoting Wnt activation and contributing to cyst formation.

PMID- 22654114
TI  - Proteomic identification of glycosylphosphatidylinositol anchor-dependent
      membrane proteins elevated in breast carcinoma.
AB  - The glycosylphosphatidylinositol (GPI) anchor is a lipid and glycan modification
      added to the C terminus of certain proteins in the endoplasmic reticulum by the
      activity of a multiple subunit enzyme complex known as the GPI transamidase
      (GPIT). Several subunits of GPIT have increased expression levels in breast
      carcinoma. In an effort to identify GPI-anchored proteins and understand the
      possible role of these proteins in breast cancer progression, we employed a
      combination of strategies. First, alpha toxin from Clostridium septicum was used
      to capture GPI-anchored proteins from human breast cancer tissues, cells, and
      serum for proteomic analysis. We also expressed short interfering RNAs targeting
      the expression of the GPAA1 and PIGT subunits of GPIT in breast cancer cell lines
      to identify proteins in which membrane localization is dependent on GPI anchor
      addition. Comparative membrane proteomics using nano-ESI-RPLC-MS/MS led to the
      discovery of several new potential diagnostic and therapeutic targets for breast
      cancer. Furthermore, we provide evidence that increased levels of GPI anchor
      addition in malignant breast epithelial cells promotes the dedifferentiation of
      malignant breast epithelial cells in part by increasing the levels of cell
      surface markers associated with mesenchymal stem cells.

PMID- 22654113
TI  - The synthetic cannabinoid R(+)WIN55,212-2 augments interferon-beta expression via
      peroxisome proliferator-activated receptor-alpha.
AB  - We have demonstrated that R(+)WIN55,212-2, a synthetic cannabinoid that possesses
      cannabimimetic properties, acts as a novel regulator of Toll-like receptor 3
      (TLR3) signaling to interferon (IFN) regulatory factor 3 (IRF3) activation and
      IFN-beta expression, and this is critical for manifesting its protective effects
      in a murine multiple sclerosis model. Here we investigated the role of peroxisome
      proliferator-activated receptor-alpha (PPARalpha) in mediating the effects of
      R(+)WIN55,212-2 on this pathway. Data herein demonstrate that the TLR3 agonist
      poly(I:C) promotes IFN-beta expression and R(+)WIN55,212-2 enhances TLR3-induced
      IFN-beta expression in a stereoselective manner via PPARalpha. R(+)WIN55,212-2
      promotes increased transactivation and expression of PPARalpha. Using the
      PPARalpha antagonist GW6471, we demonstrate that R(+)WIN55,212-2 acts via
      PPARalpha to activate JNK, activator protein-1, and positive regulatory domain IV
      to transcriptionally regulate the IFN-beta promoter. Furthermore, GW6471
      ameliorated the protective effects of R(+)WIN55,212-2 during the initial phase of
      experimental autoimmune encephalomyelitis. Overall, these findings define
      PPARalpha as an important mediator in manifesting the effects of R(+)WIN55,212-2
      on the signaling cascade regulating IFN-beta expression. The study adds to our
      molecular appreciation of potential therapeutic effects of R(+)WIN55,212-2 in
      multiple sclerosis.

PMID- 22654115
TI  - Mapping of potent and specific binding motifs, GLOGEN and GVOGEA, for integrin
      alpha1beta1 using collagen toolkits II and III.
AB  - Integrins are well characterized cell surface receptors for extracellular matrix
      proteins. Mapping integrin-binding sites within the fibrillar collagens
      identified GFOGER as a high affinity site recognized by alpha2beta1, but with
      lower affinity for alpha1beta1. Here, to identify specific ligands for
      alpha1beta1, we examined binding of the recombinant human alpha1 I domain, the
      rat pheochromocytoma cell line (PC12), and the rat glioma Rugli cell line to our
      collagen Toolkit II and III peptides using solid-phase and real-time label-free
      adhesion assays. We observed Mg(2+)-dependent binding of the alpha1 I domain to
      the peptides in the following rank order: III-7 (GLOGEN), II-28 (GFOGER), II-7
      and II-8 (GLOGER), II-18 (GAOGER), III-4 (GROGER). PC12 cells showed a similar
      profile. Using antibody blockade, we confirmed that binding of PC12 cells to
      peptide III-7 was mediated by integrin alpha1beta1. We also identified a new
      alpha1beta1-binding activity within peptide II-27. The sequence GVOGEA bound
      weakly to PC12 cells and strongly to activated Rugli cells or to an activated
      alpha1 I domain, but not to the alpha2 I domain or to C2C12 cells expressing
      alpha2beta1 or alpha11beta1. Thus, GVOGEA is specific for alpha1beta1. Although
      recognized by both alpha2beta1 and alpha11beta1, GLOGEN is a better ligand for
      alpha1beta1 compared with GFOGER. Finally, using biosensor assays, we show that
      although GLOGEN is able to compete for the alpha1 I domain from collagen IV
      (IC(50) ~3 MUm), GFOGER is much less potent (IC(50) ~90 MUm), as shown
      previously. These data confirm the selectivity of GFOGER for alpha2beta1 and
      establish GLOGEN as a high affinity site for alpha1beta1.

PMID- 22654116
TI  - A Specific interaction between SecA2 and a region of the preprotein adjacent to
      the signal peptide occurs during transport via the accessory Sec system.
AB  - The accessory Sec systems of streptococci and staphylococci mediate the transport
      of a family of large, serine-rich glycoproteins to the bacterial cell surface.
      These systems are comprised of SecA2, SecY2, and three core accessory Sec
      proteins (Asp1-3). In Streptococcus gordonii, transport of the serine-rich
      glycoprotein GspB requires both a unique 90-residue N-terminal signal peptide and
      an adjacent 24-residue segment (the AST domain). We used in vivo site-specific
      photo-cross-linking to identify proteins that interact with the AST domain during
      transport. To facilitate this analysis, the entire accessory Sec system of S.
      gordonii was expressed in Escherichia coli. The determinants of GspB trafficking
      to the accessory Sec system in E. coli matched those in S. gordonii, establishing
      the validity of this approach. When the photo-cross-linker was placed within the
      AST domain, the preprotein was found to cross-link to SecA2. Importantly, no
      cross-linking to SecA was detected. Cross-linking of the N-terminal end of the
      AST domain to SecA2 occurred regardless of whether Asp1-3 were present. However,
      cross-linking to the C-terminal end was dependent on the Asps. The combined
      results indicate that full engagement of the AST domain by SecA2 is modulated by
      one or more of the Asps, and suggest that this process is important for
      initiating transport.

PMID- 22654117
TI  - Polydom/SVEP1 is a ligand for integrin alpha9beta1.
AB  - A variety of proteins, including tenascin-C and osteopontin, have been identified
      as ligands for integrin alpha9beta1. However, their affinities for integrin
      alpha9beta1 are apparently much lower than those of other integrins (e.g.
      alpha3beta1, alpha5beta1, and alpha8beta1) for their specific ligands, leaving
      the possibility that physiological ligands for integrin alpha9beta1 still remain
      unidentified. In this study, we found that polydom (also named SVEP1) mediates
      cell adhesion in an integrin alpha9beta1-dependent manner and binds directly to
      recombinant integrin alpha9beta1 with an affinity that far exceeds those of the
      known ligands. Using a series of recombinant polydom proteins with N-terminal
      deletions, we mapped the integrin-binding site to the 21st complement control
      protein domain. Alanine-scanning mutagenesis revealed that the EDDMMEVPY sequence
      (amino acids 2636-2644) in the 21st complement control protein domain was
      involved in the binding to integrin alpha9beta1 and that Glu(2641) was the
      critical acidic residue for the integrin binding. The importance of this sequence
      was further confirmed by integrin binding inhibition assays using synthetic
      peptides. Immunohistochemical analyses of mouse embryonic tissues showed that
      polydom colocalized with integrin alpha9 in the stomach, intestine, and other
      organs. Furthermore, in situ integrin alpha9beta1 binding assays using frozen
      mouse tissues showed that polydom accounts for most, but not all, of the integrin
      alpha9beta1 ligands in tissues. Taken together, the present findings indicate
      that polydom is a hitherto unknown ligand for integrin alpha9beta1 that functions
      as a physiological ligand in vivo.

PMID- 22654118
TI  - Identification of cell adhesive sequences in the N-terminal region of the laminin
      alpha2 chain.
AB  - The laminin alpha2 chain is specifically expressed in the basement membrane
      surrounding muscle and nerve. We screened biologically active sequences in the
      mouse laminin N-terminal region of alpha2 chain using 216 soluble peptides and
      three recombinant proteins (rec-a2LN, rec-a2LN+, and rec-a2N) by both the peptide
      or protein-coated plate and the peptide-conjugated Sepharose bead assays. Ten
      peptides showed cell attachment activity in the plate assay, and 8 peptides were
      active in the bead assay. Seven peptides were active in the both assays. Five
      peptides promoted neurite outgrowth with PC12 cells. To clarify the cellular
      receptors, we examined the effects of heparin and EDTA on cell attachment to 11
      active peptides. Heparin inhibited cell attachment to 10 peptides, and EDTA
      significantly affected only A2-8 peptide (YHYVTITLDLQQ, mouse laminin alpha2
      chain, 117-128)-mediated cell attachment. Cell attachment to A2-8 was also
      specifically inhibited by anti-integrin beta1 and anti-integrin alpha2beta1
      antibodies. These results suggest that A2-8 promotes an integrin alpha2beta1
      mediated cell attachment. The rec-a2LN protein, containing the A2-8 sequence,
      bound to integrin alpha2beta1 and cell attachment to rec-a2LN was inhibited by A2
      8 peptide. Further, alanine substitution analysis of both the A2-8 peptide and
      the rec-a2LN+ protein revealed that the amino acids Ile-122, Leu-124, and Asp-125
      were involved in integrin alpha2beta1-mediated cell attachment, suggesting that
      the A2-8 site plays a functional role as an integrin alpha2beta1 binding site in
      the LN module. These active peptides may provide new insights on the molecular
      mechanism of laminin-receptor interactions.

PMID- 22654119
TI  - Optimal intensity shock wave promotes the adhesion and migration of rat
      osteoblasts via integrin beta1-mediated expression of phosphorylated focal
      adhesion kinase.
AB  - To search for factors promoting bone fracture repair, we investigated the effects
      of extracorporeal shock wave (ESW) on the adhesion, spreading, and migration of
      osteoblasts and its specific underlying cellular mechanisms. After a single
      period of stimulation by 10 kV (500 impulses) of shock wave (SW), the adhesion
      rate was increased as compared with the vehicle control. The data from both wound
      healing and transwell tests confirmed an acceleration in the migration of
      osteoblasts by SW treatment. RT-PCR, flow cytometry, and Western blotting showed
      that SW rapidly increased the surface expression of alpha5 and beta1 subunit
      integrins, indicating that integrin beta1 acted as an early signal for ESW
      induced osteoblast adhesion and migration. It has also been found that a
      significant elevation occurred in the expression of phosphorylated beta-catenin
      and focal adhesion kinase (FAK) at the site of tyrosine 397 in response to SW
      stimulation after the increasing expression of the integrin beta1 molecule. When
      siRNAs of integrin alpha5 and beta1 subunit were added, the level of FAK
      phosphorylation elevated by SW declined. Interestingly, the adhesion and
      migration of osteoblasts were decreased when these siRNA reagents as well as the
      ERK1/2 signaling pathway inhibitors, U0126 and PD98059, were present. Further
      studies demonstrated that U0126 could inhibit the downstream integrin-dependent
      signaling pathways, such as the FAK signaling pathway, whereas it had no
      influence on the synthesis of integrin beta1 molecule. In conclusion, these data
      suggest that ESW promotes the adhesion and migration of osteoblasts via integrin
      beta1-mediated expression of phosphorylated FAK at the Tyr-397 site; in addition,
      ERK1/2 are also important for osteoblast adhesion, spreading, migration, and
      integrin expression.

PMID- 22654120
TI  - Timing of voice breaking in males associated with growth and weight gain across
      the life course.
AB  - BACKGROUND: In contrast to the many studies in females, there are few data in
      males on the relationships between childhood growth and weight gain and the
      timing of pubertal maturation and its relevance to adult body mass index (BMI)
      and body composition. METHODS: A total of 2008 males in the 1946 British Birth
      Cohort Study had assessment of pubertal status including voice-breaking status
      (no change, starting, or complete) at age 14 yr. These responses were related to
      growth measurements at birth (weight only) and at 2, 4, 6, 7, 11, 14, 20, 26, 36,
      43, 53, and 60-64 yr. Body composition was assessed by dual-energy x-ray
      absorptiometry at 60-64 yr. RESULTS: Males with more advanced voice-breaking
      status at age 14 yr had similar birth weights compared with other males; they
      showed faster weight gain from 0-2 yr and had higher mean weight and BMI at age 2
      yr. Subsequently, they continued to accelerate in weight and BMI, and also in
      height, and maximum differences in body size were seen at age 14 yr. Adult height
      did not differ between groups, but males with advanced voice breaking had higher
      adult BMI and greater whole-body lean mass and greater android fat mass at 60-64
      yr. CONCLUSION: Similar to females with earlier menarche, the trajectory to
      earlier sexual maturation in males is manifested by faster early postnatal growth
      and weight gain and leads to higher adult BMI. Timing of pubertal maturation has
      potential relevance to adult disease risks in males. We also describe conditional
      height difference in sd score as a proxy marker of pubertal timing in males.

PMID- 22654122
TI  - Editorial: lipids: fueling the fire in tuberculosis?

PMID- 22654123
TI  - Editorial: (CD)40 winks to prevent CD8+ T cell lethargy.

PMID- 22654125
TI  - The Vegetative State and the Science of Consciousness.
AB  - Consciousness in experimental subjects is typically inferred from reports and
      other forms of voluntary behaviour. A wealth of everyday experience confirms that
      healthy subjects do not ordinarily behave in these ways unless they are
      conscious. Investigation of consciousness in vegetative state patients has been
      based on the search for neural evidence that such broad functional capacities are
      preserved in some vegetative state patients. We call this the standard approach.
      To date, the results of the standard approach have suggested that some vegetative
      state patients might indeed be conscious, although they fall short of being
      demonstrative. The fact that some vegetative state patients show evidence of
      consciousness according to the standard approach is remarkable, for the standard
      approach to consciousness is rather conservative, and leaves open the pressing
      question of how to ascertain whether patients who fail such tests are conscious
      or not. We argue for a cluster-based 'natural kind' methodology that is adequate
      to that task, both as a replacement for the approach that currently informs
      research into the presence or absence of consciousness in vegetative state
      patients and as a methodology for the science of consciousness more generally.

PMID- 22654127
TI  - Duplicity in pet food marketing--a comment.

PMID- 22654128
TI  - Duplicity in pet food marketing--a reply.

PMID- 22654121
TI  - Trauma equals danger--damage control by the immune system.
AB  - Traumatic injuries induce a complex host response that disrupts immune system
      homeostasis and predisposes patients to opportunistic infections and inflammatory
      complications. The response to injuries varies considerably by type and severity,
      as well as by individual variables, such as age, sex, and genetics. These
      variables make studying the impact of trauma on the immune system challenging.
      Nevertheless, advances have been made in understanding how injuries influence
      immune system function as well as the immune cells and pathways involved in
      regulating the response to injuries. This review provides an overview of current
      knowledge about how traumatic injuries affect immune system phenotype and
      function. We discuss the current ideas that traumatic injuries induce a unique
      type of a response that may be triggered by a combination of endogenous danger
      signals, including alarmins, DAMPs, self-antigens, and cytokines. Additionally,
      we review and propose strategies for redirecting injury responses to help restore
      immune system homeostasis.

PMID- 22654129
TI  - Duplicity in pet food marketing--a reply.

PMID- 22654130
TI  - Defensive medicine--a comment.

PMID- 22654131
TI  - Heartworm resistance.

PMID- 22654132
TI  - An ethicist's commentary on racehorse abuse.

PMID- 22654133
TI  - Blastomycotic osteomyelitis associated with severe lameness in a horse.
AB  - A 12-year-old Quarter horse gelding was presented for evaluation of severe right
      forelimb lameness, 2 draining tracts over the lateral aspect of the right
      proximal antebrachium, and weight loss. A presumptive diagnosis of blastomycotic
      osteomyelitis was established based on radiographs and cytology of the exudate.
      This diagnosis was confirmed at necropsy.

PMID- 22654134
TI  - A case of hypertrophic osteoarthropathy in a Belgian blue cow.
AB  - A 12-year-old cow was presented with chronic respiratory disease and lameness.
      Chronic pleuritis, pneumonia, and bronchial carcinoma were found as well as
      periosteal proliferation on limb bones. Ancillary tests and necropsy confirmed a
      combined pathology of pulmonary inflammation and neoplasm, and hypertrophic
      pulmonary osteopathy.

PMID- 22654135
TI  - Asymptomatic encephalitis in calves experimentally infected with bovine
      herpesvirus-5.
AB  - This study demonstrated that bovine herpesvirus 5 (BoHV)-5 infected calves can
      develop encephalitis and remain asymptomatic. Seven calves were infected
      intranasally and monitored for 30 days. Cerebrospinal fluid (CSF) analysis was
      performed from the onset of neurological signs. Multiple sections of brain and
      the trigeminal ganglion were submitted to histopathology. Virus detection (PCR
      and isolation) was performed on CSF and tissues. Four calves developed signs of
      neurologic disease and died. Three calves remained asymptomatic and were
      euthanized 30 days post-infection. Cerebrospinal fluid mononuclear pleocytosis
      occurred in symptomatic and asymptomatic calves. BoHV-5 was isolated and viral
      DNA was detected in multiple areas of the encephalon of all calves. The viral DNA
      was detected in the CSF of 2 calves showing neurological signs. Histologically,
      inflammation was noted in the brain of all calves and confirmed that the
      encephalitis caused by BoHV-5 may be mild and asymptomatic.

PMID- 22654136
TI  - Surgical versus conservative management of patella fractures in cats: a
      retrospective study.
AB  - This study compared the clinical outcome in cats with patella fractures treated
      by surgery to those treated conservatively. Six cats with 9 patella fractures
      were treated. Six fractures were treated surgically and 3 were treated
      conservatively. Medical records of all 6 patients were reviewed for age, breed,
      gender, trauma, and fracture conformation. All patients had follow-up which
      consisted of a physical examination, radiographs, and an interview with the
      client between 1 and 4.5 y after surgery or diagnosis. All cats treated
      conservatively returned to normal activity with no gait abnormalities. In cats
      that had surgery, 4/6 had breakdown of the surgical repair but all cats went on
      to full recovery with normal activity and gait. The conclusions of this
      preliminary study are that surgical repair of cat patella fractures has a high
      rate of implant failure and that conservative management of cat patella fractures
      results in excellent clinical outcome.

PMID- 22654137
TI  - The prevalence of intestinal parasites in dogs and cats in Calgary, Alberta.
AB  - The prevalence of endoparasites was evaluated in 619 dogs and 153 cats in the
      Calgary, Alberta region. Both homed and shelter-sourced pets were evaluated, and
      prevalence was assessed in various age groups. The overall endoparasite
      prevalence was 16.5% in canine samples and 7.2% in feline samples. The most
      common intestinal parasites in dogs were Giardia (8.1%) and ascarids (4.2%). The
      most common feline endoparasite was ascarids (6.5%). This study will help
      veterinarians to better plan diagnostic and preventative strategies with regard
      to companion animal intestinal parasites.

PMID- 22654139
TI  - Magnetic resonance and computed tomographic features of 4 cases of canine
      congenital thoracic vertebral anomalies.
AB  - Magnetic resonance and computed tomography features of 4 cases of canine
      congenital vertebral anomalies (CVAs) are discussed. Two of the cases represent
      unusual presentations for such anomalies that commonly affect screw-tail or toy
      breeds. Moreover, the combination of CVAs and a congenital peritoneo-pericardial
      diaphragmatic hernia has never before been imaged.

PMID- 22654138
TI  - Evaluation of the zoonotic potential of Giardia duodenalis in fecal samples from
      dogs and cats in Ontario.
AB  - This study determined the distribution and zoonotic potential of Giardia
      duodenalis assemblage types among canine and feline fecal samples from Ontario.
      The effectiveness of Giardia assemblage typing methods by sequencing the genes of
      small subunit ribosomal RNA (ssu-rRNA), beta-giardin (bg), glutamate
      dehydrogenase (gdh), and triose phosphate isomerase (tpi) was evaluated
      simultaneously. From 2008 to 2010, 118 canine and 15 feline Giardia positive
      fecal samples were tested. The ssu-rRNA sequencing method typed 64% (75/118) and
      87% (13/15) of the Giardia-positive canine and feline samples, respectively.
      Among the typeable samples, 68% (51/75) of canine samples contained G. duodenalis
      assemblage D and 31% (23/75) contained G. duodenalis assemblage C (both non
      zoonotic assemblage types). Only 1% (1/75) of the typeable canine samples
      contained a potentially zoonotic assemblage B. In contrast, 100% (13/13) of the
      typeable feline samples contained potentially zoonotic assemblages A (n = 12) or
      B (n = 1).

PMID- 22654140
TI  - Mycotic encephalitis, sinus osteomyelitis, and guttural pouch mycosis in a 3-year
      old Arabian colt.
AB  - Mycotic encephalitis caused severe ataxia and other neurologic deficits in a
      horse. The finding of a single, large focus of cerebral malacia, with
      histopathologic evidence of fungal elements, suggested infection was a result of
      direct transfer from the frontal sinuses, rather than hematogenous spread from
      the guttural pouch.

PMID- 22654141
TI  - Seroprevalence of bovine viral diarrhea virus neutralizing antibodies in finisher
      hogs in Ontario swine herds and targeted diagnostic testing of 2 suspect herds.
AB  - A pilot study was initiated to determine the seroprevalence of bovine viral
      diarrhea virus (BVDV) neutralizing antibodies in finisher hogs in Ontario swine
      herds, including 2 swine herds with clinical syndromes suspicious of BVDV. No
      herds were positive for BVDV antibodies by virus neutralization. The 2 swine
      herds with clinical disease suggestive of pestivirus infection were also negative
      for antibodies to BVDV in indirect fluorescent antibody assays. Prevalence of
      BVDV in Ontario swine farms is negligible.

PMID- 22654142
TI  - Pemphigus foliaceus in a juvenile Cashmere goat, and outcome after prednisolone
      and methylprednisolone therapy.
AB  - A juvenile Cashmere goat was evaluated and treated for generalized pustular and
      crusting dermatitis. A diagnosis of pemphigus foliaceus was made based on
      histopathology and immunohistochemistry. Treatment with prednisolone resulted in
      resolution of the lesions. Despite tapering doses and combination with
      methylprednisolone for monthly maintenance, the kid was euthanized for poor
      growth and fiber quality.

PMID- 22654143
TI  - Exophthalmos due to multicentric B-cell lymphoma in a goat.
AB  - Multicentric B-cell lymphoma with extensive retrobulbar involvement was diagnosed
      in a 6-year-old Nubian goat that was presented with conjunctival swelling and
      exophthalmos. Serologic testing for bovine leukemia virus (BLV) was negative.
      Postmortem computed tomography aided in identification of the extent of soft
      tissue and bone lesions.

PMID- 22654145
TI  - Half-empty and half-full communication: the practitioner.

PMID- 22654144
TI  - Ova of Dioctophyme renale in a canine struvite urolith.
AB  - This report describes light and scanning electron microscopic appearance of an
      ovum from the giant kidney worm, Dioctophyme renale found in the nidus and stone
      layer of a struvite calculus. The stone had been surgically removed from the
      bladder of a 4-year-old spayed female mixed breed dog from northern Ontario.

PMID- 22654146
TI  - Orthopedic hardware and equipment for the beginner. Part 2: plates and screws.

PMID- 22654147
TI  - Avoiding the "no".

PMID- 22654148
TI  - Methodological Encounters with the Phenomenal Kind.
AB  - Block's well-known distinction between phenomenal consciousness and access
      consciousness has generated a large philosophical literature about putative
      conceptual connections between the two. The scientific literature about whether
      they come apart in any actual cases is rather smaller. Empirical evidence
      gathered to date has not settled the issue. Some put this down to a fundamental
      methodological obstacle to the empirical study of the relation between phenomenal
      consciousness and access consciousness. Block (2007) has drawn attention to the
      methodological puzzle and attempted to answer it. While the evidence Block points
      to is relevant and important, this paper puts forward a more systematic framework
      for addressing the puzzle. To give it a label, the approach is to study
      phenomenal consciousness as a natural kind. The approach allows consciousness
      studies to move beyond initial means of identifying instances of the kind like
      verbal report, and to find its underlying nature. It is well-recognised that
      facts about an underlying kind may allow identification of instances of the kind
      that do not match the initial means of identification (cp. non-liquid samples of
      water). This paper shows that the same method can be deployed to investigate
      phenomenal consciousness independently of access consciousness.

PMID- 22654149
TI  - Welfare as Maternity Leave? Exemptions from Welfare Work Requirements and
      Maternal Employment.
AB  - In some states, the Temporary Assistance for Needy Families (TANF) program offers
      the equivalent of paid maternity leave without job protection to low-income,
      single mothers of infants. Age-of-youngest-child (AYC) exemptions waive work
      requirements for TANF recipients after the birth of a child, generally for 3-12
      months, depending on the state. This study uses data from the Current Population
      Survey (1998-2008) to examine whether the availability and length of AYC
      exemptions are predictive of rates of employment, work, and full-time work among
      low-educated single mothers with infants. The analysis uses the difference-in
      differences (DD) technique, a comparison of outcomes under different policy
      treatments and between treatment and comparison groups. The results suggest that
      AYC exemptions are not related to employment or work rates but that living in a
      state with no AYC exemption is strongly and positively associated with rates of
      full-time work among low-educated mothers with infants.

PMID- 22654150
TI  - SYNTHESIS OF N-SUBSTITUTED CARBONYLAMINO-1,2,3,6-TETRAHYDROPYRIDINES AS POTENTIAL
      ANTI-INFLAMMATORY AGENTS.
AB  - Several N-substituted carbonyl/sulfonylamino-1,2,3,6-tetrahydropyridines (5a-i
      and 9a, b) were synthesized via sodium borohydride reduction of the corresponding
      N-substitutedimino-pyridinium ylides (4a-i and 8a, b) in absolute ethanol.

PMID- 22654151
TI  - Role of biotechnology in the treatment of polyester fabric.
AB  - Poly (ethylene terephthalate) fibre [PET] is the commonly used fibre for majority
      of end-use applications, however, the desire for improved textile properties such
      as wettability or hydrophilicity are increasing. Biotechnology can be defined as
      the application of scientific and engineering to the processing of materials by
      biological agents to provide goods and services. The environmental issues
      associated with the textile processing are not new. Currently and in the years to
      come, besides lower cost of operation, improved durability, wear comfort and
      development of new attributes for textiles, the new criteria for judging the new
      processes is ecology. This paves the way for biotechnology. This article throws
      light on the applications of enzymes for the treatment of polyester fabrics.

PMID- 22654153
TI  - Phylogenetic characterization of archaea in saltpan sediments.
AB  - A study was undertaken to investigate the presence of archaeal diversity in
      saltpan sediments of Goa, India by 16S rDNA-dependent molecular phylogeny. Small
      subunit rRNA (16S rDNA) from saltpan sediment metagenome were amplified by
      polymerase chain reaction (PCR) using primers specific to the domain archaea. 10
      unique phylotypes were obtained by PCR based RFLP of 16S rRNA genes using
      endonuclease Msp 1, which was most suitable to score the genetic diversity. These
      phylotypes spanned a wide range within the domain archaea including both
      crenarchaeota and euryarcheaota. None of the retrieved crenarchaeota sequences
      could be grouped with previously cultured crenarchaeota however; two sequences
      were related with haloarchaea. Most of the sequences determined were closely
      related to the sequences that had been previously obtained from metagenome of a
      variety of marine environments. The phylogenetic study of a site investigated for
      the first time revealed the presence of low archaeal population but showed yet
      unclassified species, may specially adapted to the salt pan sediment of Goa.

PMID- 22654154
TI  - Mutation-Screening in l-(+)-Lactic Acid Producing Strains by Ion Implantation.
AB  - In this paper, in order to obtain some industrial strains with high yield of l
      (+)-lactic acid, the wild type strain Lactobacillus casei CICC6028 was mutated by
      nitrogen ions implantation. By study, it was found that the high positive
      mutation rate was obtained when the output power was 10 keV and the dose of N(+)
      implantation was 50 * 2.6 * 10(13) ions/cm(2). In addition, the initial screening
      methods were also studied, and it was found that the transparent halos method was
      unavailable, for some high yield strains of l-(+)-lactic acid were missed. Then a
      mutant strain which was named as N-2 was isolated, its optimum fermentation
      temperature was 40 degrees C and the l-(+)-lactic acid yield was 136 g/l compared
      to the original strain whose optimum fermentation temperature was 34 degrees C
      and l-(+)-lactic acid production was 98 g/l. Finally, High Performance Liquid
      Chromatography method was used to analyze the purity of l-(+)-lactic acid that
      was produced by the mutant N-2, and the result showed the main production of N-2
      was l-(+)-lactic acid.

PMID- 22654152
TI  - Role of heat shock proteins in diseases and their therapeutic potential.
AB  - Heat shock proteins are ubiquitously expressed intracellular proteins and act as
      molecular chaperones in processes like protein folding and protein trafficking
      between different intracellular compartments. They are induced during stress
      conditions like oxidative stress, nutritional deficiencies and radiation. They
      are released into extracellular compartment during necrosis. However, recent
      research findings highlights that, they are not solely present in cytoplasm, but
      also released into extracellular compartment during normal conditions and even in
      the absence of necrosis. When present in extracellular compartment, they have
      been shown to perform various functions like antigen presentation, intercellular
      signaling and induction of pro-inflammatory cytokines. Heat shock proteins
      represents as dominant microbial antigens during infection. The phylogenetic
      similarity between prokaryotic and eukaryotic heat shock proteins has led to
      proposition that, microbial heat shock proteins can induce self reactivity to
      host heat shock proteins and result in autoimmune diseases. The self-reactivity
      of heat shock proteins protects host against disease by controlling induction and
      release of pro-inflammatory cytokines. However, antibodies to self heat shock
      proteins haven been implicated in pathogenesis of autoimmune diseases like
      arthritis and atherosclerosis. Some heat shock proteins are potent inducers of
      innate and adaptive immunity. They activate dendritic cells and natural killer
      cells through toll-like receptors, CD14 and CD91. They play an important role in
      MHC-antigen processing and presentation. These immune effector functions of heat
      shock proteins are being exploited them as therapeutic agents as well as
      therapeutic targets for various infectious diseases and cancers.

PMID- 22654155
TI  - Detection of Integrons from Escherichia coli Isolates Obtained from Some Selected
      Animals in Republic of Korea.
AB  - We detected integrons in 298 of 1106 Escherichia coli isolates obtained from the
      feces of pigs, chicken, ducks and elks. Among the sources there was higher number
      of integrons detected in the isolates of pigs. No integron was found in the
      isolates of gooses. Detection of lot of integrons in these isolates discovers the
      possibility of spread of antibiotic resistance genes in the environment.

PMID- 22654156
TI  - Application of Polymerase Chain Reaction to Detect HIV-1 DNA in Pools of Dried
      Blood Spots.
AB  - Nucleic acid tests that detect HIV infection at an early phase are available and
      have been applied on individual dried blood spot (DBS). The present study was
      undertaken with an aim to evaluate the feasibility of performing PCR for HIV-1
      DNA on pools of DBS as an alternative to individual testing. Standardization of
      PCR by a modified Amplicor HIV-1 DNA assay version 1.5 (Roche molecular
      diagnostics, USA), on pooled DBS was performed using five confirmed HIV reactive
      samples with known low viral load of HIV-1 and HIV non-reactive samples in pools
      of 5, 10 and 20 DBS. After successful standardization of pooling procedure, a
      total of 183 pools (of 10 DBS each) were prepared from 1,823 DBS samples,
      collected from a population-based study that tested negative for HIV antibodies
      and p24 antigen. All these pools were screened for HIV-1 DNA by the Amplicor
      assay. Standardization of pooling procedure indicated that pooling of 10 DBS gave
      an optimum result. Out of 183 pools tested, one pool of 10 samples was positive
      and of these ten DBS that were tested individually to identify the positive DBS,
      one sample was detected to be positive for HIV-1 DNA. Our study demonstrates that
      PCR for HIV-1 DNA can be successfully performed on pools of DBS. However, this
      may be needed only on specialized studies of HIV and not for routine epidemiology
      studies as only a very small fraction of cases would be missed if only
      antibody/antigen testing were done.

PMID- 22654157
TI  - Regulation of Saccharomyces cerevisiae Plasma membrane H(+)-ATPase (Pma1) by
      Dextrose and Hsp30 during Exposure to Thermal Stress.
AB  - Pma1p is an essential plasma membrane H(+)-pump in Saccharomyces cerevisiae that
      pumps out H(+) at the expense of cellular ATP. Its activity is induced by glucose
      at 30 degrees C and is inhibited by Hsp30 during exposure to heat shock
      conditions. To further investigate the regulation of Pma1 function by glucose and
      Hsp30 during exposure to thermal stress, we estimated Pma1 activity, its protein
      levels and ser-phosphorylation status in membrane fractions isolated from BY4741
      and hsp30Delta cells grown in dextrose and sorbitol at 30 degrees C, and
      following exposure at 40 degrees C for 30 min. Our results demonstrate that Pma1
      activity and protein levels were reduced in Hsp30(+) cells following exposure to
      thermal stress in dextrose media. The above was not observed in hsp30Delta cells
      wherein Pma1 activity did not decrease following exposure to similar conditions.
      Although Pma1p levels decreased in heat-shocked hsp30Delta cells, it was lower
      compared to that observed in Hsp30(+) cells. Total ser-phosphorylation of Pma1
      also showed a decrease following exposure to heat shock condition in dextrose
      media in both BY4741 and hsp30Delta cells. Its levels were also reduced in BY4741
      cells upon heat shock treatment in sorbitol unlike that observed in hsp30Delta
      cells wherein it was increased. Taken together the above indicate that heat shock
      induced reduction in Pma1 activity and protein levels in dextrose media required
      Hsp30. To examine functional interactions between dextrose utilization, Hsp30 and
      the regulation of various aspects of Pma1, we determined if dextrose regulated
      other functions attributed to Hsp30. Results demonstrate that the deletion of
      HSP30 rendered cells dependent on dextrose utilization for survival during
      exposure to lethal heat stress. Our study has hence been able to establish a
      functional relationship between glucose utilization, Hsp30 function and the
      regulation of Pma1 activity. Finally, since the deletion of HSP30 renders Pma1p
      levels and its activity unresponsive to thermal stress in dextrose media, we
      concluded that Hsp30 is necessary to maintain Pma1 in a regulation competent
      conformation. Hsp30 may thus act as a chaperone in the S. cerevisiae plasma
      membrane.

PMID- 22654158
TI  - Decolorization of Azo Dye (Orange MR) by an Autochthonous Bacterium, Micrococcus
      sp. DBS 2.
AB  - Soil and sediment samples obtained from Orange MR dye contaminated habitat were
      screened for heterotrophic bacterial population. The heterotrophic bacterial
      density of dye-contaminated soil was 2.14 * 10(6) CFU/g. The generic composition
      of heterotrophic bacterial population was primarily composed of 10% of Proteus
      sp., 15% Aeromonas sp., 20% Bacillus sp., 25% Pseudomonas sp. and 30% Micrococcus
      sp. The bacterial strain that decolorized the azo dye Orange MR up to 900 ppm was
      identified as Micrococcus sp. The optimum inoculum load, pH and temperature were
      found to be 5%, 6 and 35 degrees C, respectively. The rate of decolorization was
      assessed using spectrophotometer at 530 nm and the percentage of decolorization
      was ascertained. The autochthonous bacterial isolate was able to utilize the dye
      as both nitrogen and carbon source.

PMID- 22654159
TI  - Stability Study of Crude Dextransucrase from Leuconostoc citreum NRRL B-742.
AB  - In the present work, the stability of crude dextransucrase from Leuconostoc
      citreum B-742 was evaluated in synthetic and in cashew apple juice culture broth.
      Optimum stability conditions for dextransucrase from L. citreum B-742 were
      different from the reported for its parental industrial strain enzyme (L.
      mesenteroides B-512F). Crude dextransucrase, from L. citreum B-742, produced
      using cashew apple juice as substrate, presented higher stability than the crude
      enzyme produced using synthetic culture medium, showing the same behavior
      previously reported for dextransucrase from L. mesenteroides B-512F. The crude
      enzyme presented good stability in cashew apple juice for 48 h at 25 degrees C
      and pH 6.5.

PMID- 22654160
TI  - Autohydrolysed Tilapia nilotica Fish Viscera as a Peptone Source in Bacteriocin
      Production.
AB  - Fish processing generates large amounts of solid and liquid wastes. Many
      different by-products have been produced from fish processing wastes. Studies on
      solubilization of Bolti fish (Tilapia nilotica) viscera by endogenous enzymes at
      different pHs are described. Hydrolysis reactions were conducted with freshly
      thawed viscera utilizing an initial temperature gradient and terminated at
      various time points by heat inactivation of the enzymes. Various peptones
      obtained from hydrolysed visceral homogenates of Bolti fish residues showed their
      suitability for promoting the growth of lactic acid bacteria (mainly
      Lactobacillus sake Lb 706), microorganisms with particularly complex nutritional
      requirements especially peptidic sources. The assay of several treatments with L.
      sakei Lb 706, producer of the bacteriocin sakacin A, demonstrated that optimum
      conditions for biomass and bacteriocin production only imply a brief
      autohydrolysis at room temperature. The results showed that the Bolti fish
      hydrolysates gave remarkable results to those found in costly commercial media,
      specifically recommended for culturing and large-scale production of lactic acid
      bacteria.

PMID- 22654161
TI  - Chemical Characterization, Crossfeeding and Uptake Studies on Hydroxamate
      Siderophore of Alcaligenes faecalis.
AB  - We report the production of two types of siderophores namely catecholate and
      hydroxamate in modified succinic acid medium (SM) from Alcaligenes faecalis. Two
      fractions of siderophores were purified on amberlite XAD, major fraction was
      hydroxamate type having a lambda(max) at 224 nm and minor fraction appeared as
      catecholate with a lambda(max) of 264 nm. The recovery yield obtained from major
      and minor fractions was 297 and 50 mg ml(-1) respectively. The IEF pattern of XAD
      4 purified siderophore suggested the pI value of 6.5. Cross feeding studies
      revealed that A. faecalis accepts heterologous as well as self (hydroxamate)
      siderophore in both free and iron complexed forms however; the rate of
      siderophore uptake was more in case of siderophores complexed to iron.
      Siderophore iron uptake studies indicated the differences between hydroxamate
      siderophore of A. faecalis and Alc E, a siderophore of Alcaligenes eutrophus.

PMID- 22654162
TI  - Phenotypic and genotypic characterization of bacteriocins in enterococcal
      isolates of different sources.
AB  - A collection of 57 enterococcal isolates from different origin (including river,
      treatment plant, spring and garbage water, soil, animal, and vegetables from
      Aydin) was screened for the production of bacteriocins. Enterococci were
      identified at species levels as Enterococcus faecium (34), E. hirae (6), E.
      casseliflavus (4), E. durans (4), E. faecalis (4), E. mundtii (3) and E. avium
      (2). Of the 57 isolates 40 of them inhibited the growth of at least one indicator
      bacterium. Based on our PCR results 54 strains possesed enterocin genes. The
      genes of entA and entB were the most frequently detected structural genes among
      the PCR positive strains (54 and 53 strains, respectively) and the entB gene was
      always associated with entA gene. The highest combination of enterocin genes (24
      of 54 strains) detected was entA, entB, entP and entL50A/B. The enterocins AS-48
      and CylL(LS) genes were not found. Three enterococcal isolates, 2 E. faecium and
      1 E. hirae were not harbour any of tested enterocin genes. No correlation between
      the presence of enterocin structural genes and the origin of the strain was
      detected, also no relationship seemed to exist between the tested enterocin genes
      and the activity spectra of isolates. Genes encoding bacteriocins are widely
      disseminated among enterocci from different origin and more studies should be
      done for evaluate industrial potential of bacteriocins. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s12088-011-0143-0)
      contains supplementary material, which is available to authorized users.

PMID- 22654163
TI  - Distribution of coliphages against four e. Coli virotypes in hospital originated
      sewage sample and a sewage treatment plant in bangladesh.
AB  - The distribution of coliphages infecting different Escherichia coli virotypes
      (EHEC, EIEC, EPEC, ETEC) and an avirulent strain (K-12) in sewage system of a
      hospital and a sewage treatment plant (STP) was investigated by culture-based
      agar overlay methods. Coliphages were found in all the samples except stool
      dumping site in the sewage system of the hospital and lagoon of the STP.
      Bacteriophage count (pfu/ml) infecting E. coli strains showed the following
      ascending pattern (EHEC < EIEC < EPEC < ETEC < E coli K-12) in all the collected
      samples except one. Phages capable of infecting avirulent E. coli K-12 strains
      were present in the highest number among all the examined locations. Phages
      specific for E. coli K-12 presented high diversity in plaque size on the
      bacterial lawn. Virulent E. coli specific coliphages rarely produced plaques with
      diameter of 1-2 mm or over. Conventional agar overlay method was found to be not
      satisfactory for phage community analysis from primary stool dumping site of the
      hospital, probably due to the presence of high concentration of antimicrobial
      substances. The gradual decrease seen in the five groups of coliphage quantity
      with the ongoing treatment process and then the absolute absence of coliphages in
      the outlet of the examined treatment plant is indicative of the usefulness of the
      treatment processes practiced there.

PMID- 22654164
TI  - Genetic Diversity and Pathogenicity of Xanthomonas axonopodis Strains Inducing
      Citrus Canker Disease in Iran and South Korea.
AB  - For the first time in 1989 citrus bacterial canker disease has seen on
      Citrusaurantiifolia in southern Iran. A total of 43 strains from affected citrus
      trees, ten strains from South Korea and representative from all known five
      pathotypes of Xanthomonas axonopodis pathogenic on citrus trees were used in this
      study. Isolated strains from Iran were indistinguishable by phenotypic, FAMEs,
      and SDS-PAGE analyses but showed different host range. First group were
      pathogenic on all tested citrus seedlings including C. aurantiifolia, C.
      limettioides, C. limon, C. jambhiri, Poncirus trifoliata X C. paradisi, C.
      aurantium, C. paradise, C. medica, P. trifoliate, C. grandis, C. sinensis, C.
      reticulate and C. sinensis X P. trifoliate. Pathogenicity of the second group
      were limited to C. aurantiifolia, C. limettioides, C. limon, C. jambhiri, P.
      trifoliata X C. paradis, and C. aurantium. Among the strains studied by AFLP
      fingerprinting six clusters were found. These clusters were: (1) strains of
      pathotype C; (2) strains of pathotypes B and D; (3) strains of pathotype A
      together with the main group of the Iranian strains; (4) strains isolated from
      Korea; (5) strains of pathotype E; and (6) seven strains from Iran which made a
      completely separate cluster. Strains from pathotypes B and D could not be
      differentiated by AFLP. The tested Iranian strains belongs to the two different
      groups and strains from Korea grouped as a subcluster from main cluster of
      Iranian strains belong to the pathotype A.

PMID- 22654165
TI  - Evaluation of Volvariella volvacea Strains for Yield and Diseases/Insect-Pests
      Resistance Using Composted Substrate of Paddy Straw and Cotton Mill Wastes.
AB  - Out of the 3 parent strains and 4 single spore isolates of Volvariella volvacea
      evaluated, strain, OE-274 gave earliest yield in 11.25-11.50 days post-spawning
      in all 4 trials. The yield varied in different strains in different trials and it
      was highest in strain, OE-272 in trial 1, SSI, OE-55-08 in trial 2, and strain,
      OE-274 in trial 3 and 4. In overall average, highest yield was in strain, OE-272,
      closely followed by strain, OE-274. The number of fruiting bodies per q substrate
      also varied in different strains in different trials. Highest numbers were in
      strain, OE-272, SSIs, OE-55-08 and OE-12-22, and strain, OE-210 in trial 1, 2, 3
      and 4, respectively. Highest fruiting body wt was in strain, OE-274 in all 4
      trials. The yield during different weeks of cropping varied in different strains
      but invariably it was highest in first week, which accounted for 60-70% of the
      total yield. The fruiting bodies of strain, OE-274 were of bigger size, brownish,
      toughest and with least tendency of veil opening, while that of strain, OE-272
      and SSI, OE-55-08 were whitish to grayish-white, oblong, medium size, delicate
      and lesser tendency of veil opening. The strain, OE-274 and SSI, OE-55-08
      exhibited higher resistance against the growth of competitor moulds and
      infestations of insect-pests, while strain, OE-272 exhibited highest
      susceptibility to insect-pests infestation.

PMID- 22654166
TI  - Over-Expression of YLR162W in Saccharomyces cerevisiae Inhibits Cell
      Proliferation and Renders Cells Susceptible to the Hypoxic Conditions Induced by
      Cobalt Chloride.
AB  - YLR162W is an uncharacterized Saccharomyces cerevisiae ORF whose transcript level
      is elevated in cells under environmental stress, during alpha-factor response and
      in stationary phase. We obtained a partial cDNA clone of YLR162W by subtractive
      hybridization cloning of genes that were not expressed in a CoCl(2) resistant DNA
      synthesis mutant but expressed in its wild type counterpart. Our studies
      demonstrated that YLR162W transcript level was reduced in BY4741 cells upon
      exposure to the hypoxia mimetic agent CoCl(2), and continuous expression of full
      length YLR162W from a plasmid borne copy of the gene rendered BY4741 cells
      extremely susceptible to the hypoxic conditions induced by CoCl(2). At initial
      time points following the induction of YLR162W expression, cell cycle progression
      was inhibited with the emergence of a distinct sub-G1 peak indicative of
      apoptotic cells, mitochondrial membrane potential was also decreased along with
      an increase in the fraction of cells permeable to propidium iodide; none of the
      above was further affected by CoCl(2). The up-regulation of Ylr162wp in cells
      exposed to environmental stress and in non-replicating cells appears to be
      related to its growth inhibitory properties presented in this report.

PMID- 22654167
TI  - Outbreak of Abortions and Infertility in Thoroughbred Mares Associated with
      Waterborne Aeromonas hydrophila.
AB  - At a thoroughbred equine breeding farm near Hissar (Haryana), three mares aborted
      in their seventh month of pregnancy. The vaginal swabs of all aborted mares, and
      stomach contents, heart blood, liver, spleen and placenta of aborted fetuses
      yielded pure culture of Aeromonas hydrophila. In addition, A. hydrophila was also
      isolated from the vaginal swabs of three repeat breeding mares and faecal sample
      of a diarrheic foal. The source of infection was possibly water supply as all the
      water samples collected from taps, mother tank and storage tank were found to be
      positive for A. hydrophila. The antibiogram of all the isolates was similar
      showing resistance to ampicillin, carbenicillin, gentamicin, kanamycin and
      amikacin but sensitive to chloramphenicol, ciprofloxacin, cefuroxime,
      ceftriaxone, cotrimoxazole, cotrimazine, nitrofurantoin, streptomycin and
      tetracycline. All the 20 sera samples collected from three aborted and three
      repeat breeding, and eight in-contact mares, a diarrheic foal, three cows and two
      male buffaloes maintained at the same farm contained antibodies against A.
      hydrophila with titres ranging from 80 to 640. The water supply was instantly
      chlorinated using 0.05% sodium hypochlorite for three consecutive days and all
      the culturally positive mares were treated with intravaginal administration of 1
      g ciprofloxacin, while the foal was given nitrofurantoin for three days. After
      one month, A. hydrophila could not be isolated either from mares or from their
      environment and antibody titre in all the seropositive animals showed a declining
      trend. Later, all the aborted and repeat breeding mares were confirmed to be
      pregnant. Thus, the present study indicated that water-borne A. hydrophila might
      be associated with equine abortions and infertility, and diarrhea in newborn
      foals.

PMID- 22654168
TI  - Topical Treatment of Dermatophytic Lesion on Mice (Mus musculus) Model.
AB  - Antidermatophytic potential of three weed plants viz. Tridax procumbens L.,
      Capparis decidua (forsk) Edgew and Lantana camara L. were explored and
      experimentally induced dermatophytic lesion was topically treated in mice.
      Microbroth dilution method was carried out for determination of MIC and MFC of
      different extracts of selected plants. In animal studies, mice were
      experimentally inoculated with Trichophyton mentagrophytes and infected animals
      were topically treated with 5 mg/g terbinafine and two concentrations, i.e., 5
      and 10 mg/g of test extract ointment. Complete recovery from the infection was
      observed on 12th day of treatment for reference drug terbinafine (5 mg/g) and 10
      mg/g concentration of test extract ointment whereas 5 mg/g concentration of test
      extract ointment showed complete cure on 16th day of treatment. Fungal burden was
      also calculated by culturing skin scrapings from infected animals of different
      groups. Test extract ointment successfully treated induced dermatophytosis in
      mice without any disease recurrence incidences, thereby indicating efficacy of
      test extract as an excellent topical antifungal agent for the cure of
      dermatophytosis.

PMID- 22654169
TI  - Comparative Seroepidemiologic Analysis of Chlamydophila Pneumoniae Infection
      using Microimmunofluorescence, Enzyme Immunoassay and Neutralization Test:
      Implications for Serodiagnosis.
AB  - A seroepidemiologic study using the microimmunofluorescence (MIF) technique was
      conducted to determine the prevalence of Chlamydophila pneumoniae IgG antibodies
      among 205 healthy Singapore university undergraduates using the MRL Diagnostics
      MIF test kit. The overall seroprevalence was 35.1% with significantly higher
      seropositivity rates among males than females (48.2 vs. 18.7%, P < 0.001). A
      comparative study using the Labsystems MIF test kit was conducted on sera from
      192 students. Using the MRL MIF test as the reference, the sensitivity and
      specificity of Labsystems MIF test were 92.6 and 87.9%, respectively. A total of
      78 samples comprising 15 MIF-negative and 63 MIF-positive samples were also
      tested for complement-independent neutralizing antibodies in vitro. All the 78
      samples and 11 additional MIF-negative samples were also tested for IgM, IgG and
      IgA against C. pneumoniae by enzyme immunoassay (EIA) using the Labsystems EIA
      test kit. None of these 89 samples were seropositive for IgM. The percentages of
      IgG and IgA seropositivity increased with increasing grades of MIF-positivity.
      Among the IgG seropositive samples, 69.1% were also positive for IgA, suggesting
      that a high proportion of infected individuals also had IgA antibodies denoting
      chronicity. Neutralizing antibodies were detected in 22.2% of MIF-positive sera,
      but only in 6.7% of MIF-negative sera. 26.4 and 34.2% of samples which were IgG
      and IgA seropositive respectively also exhibited neutralizing activity. The
      percentages of MIF-positive sera with neutralizing activity increased with the
      grade of MIF positivity, i.e. 0% (1+), 7.1% (2+), 18.8% (3+), and 63.6% (4+).
      High-grade MIF positivity (particularly with MRL MIF kits) may represent a useful
      serologic marker of predictive value for neutralizing activity.

PMID- 22654170
TI  - In vitro sensitivity of Rhizobium and phosphate solubilising bacteria to
      herbicides.
AB  - Nitrogen fixing bacteria, rhizobia and phosphate solubilizing bacteria (PSB) are
      the commonly applied microbial inoculants in grain legumes (Pulses). It is
      important to apply herbicides to control weeds in order to augment yield of the
      crop. The herbicides may however, be incompatible with the microbial inoculants.
      This study compared the effect of the recommended pre-plant incorporated
      herbicide, fluchloralin (20.25 * 10(4) ppm) and pre-emergence herbicide,
      pendimethalin in two doses (9 * 10(4) and 15 * 10(4) ppm) on the growth and
      survival of mungbean Rhizobium and PSB, under laboratory conditions. These
      herbicides were also used under field conditions in conjunction with
      biofertilizers (R, PSB) to improve grain yield of mungbean. It was found that
      fluchloralin (20.25 * 10(4) ppm) and the lower dose of pendimethalin (9 * 10(4)
      ppm) had no adverse effect on growth of Rhizobium and PSB. The higher dose of
      pendimethalin (15 * 10(4) ppm) was safe on PSB but it imposed a retarding effect
      on the growth of Rhizobium.

PMID- 22654171
TI  - Storage and preservation of temperate mushroom cultures, agaricus bisporus and
      pleurotus Florida.
AB  - Two temperate mushroom cultures namely Agaricus bisporus (U-3) and Pleurotus
      florida (PAU-5) were evaluated for their physiological (linear growth and biomass
      production), biochemical (beta-1,4 endoglucanase production) and fruiting
      behaviour after preservation in 10% (v/v) glycerol and storage at room
      temperature (25-35 degrees C), -20 degrees C and -196 degrees C for 6 months with
      the objective of establishing the recovery/changes in these fungi after storage.
      Studies indicated that the viability and recovery of A. bisporus and P. florida
      is affected by the storage conditions. Both the fungi could be best stored in
      liquid nitrogen for longer durations but for regular use, conventional sub
      culturing was appropriate.

PMID- 22654172
TI  - Gut-Brain Communication is Influenced by Gut Microbes.

PMID- 22654173
TI  - Geobacter: the electric microbe! Efficient microbial fuel cells to generate
      clean, cheap electricity.

PMID- 22654174
TI  - SPY-ing into Protein Stability.

PMID- 22654175
TI  - Dynamics of neuronal bursting.

PMID- 22654177
TI  - A database of computational models of a half-center oscillator for analyzing how
      neuronal parameters influence network activity.
AB  - A half-center oscillator (HCO) is a common circuit building block of central
      pattern generator networks that produce rhythmic motor patterns in animals. Here
      we constructed an efficient relational database table with the resulting
      characteristics of the Hill et al.'s (J Comput Neurosci 10:281-302, 2001) HCO
      simple conductance-based model. The model consists of two reciprocally inhibitory
      neurons and replicates the electrical activity of the oscillator interneurons of
      the leech heartbeat central pattern generator under a variety of experimental
      conditions. Our long-range goal is to understand how this basic circuit building
      block produces functional activity under a variety of parameter regimes and how
      different parameter regimes influence stability and modulatability. By using the
      latest developments in computer technology, we simulated and stored large amounts
      of data (on the order of terabytes). We systematically explored the parameter
      space of the HCO and corresponding isolated neuron models using a brute-force
      approach. We varied a set of selected parameters (maximal conductance of
      intrinsic and synaptic currents) in all combinations, resulting in about 10
      million simulations. We classified these HCO and isolated neuron model
      simulations by their activity characteristics into identifiable groups and
      quantified their prevalence. By querying the database, we compared the activity
      characteristics of the identified groups of our simulated HCO models with those
      of our simulated isolated neuron models and found that regularly bursting neurons
      compose only a small minority of functional HCO models; the vast majority was
      composed of spiking neurons.

PMID- 22654176
TI  - The role of spiking and bursting pacemakers in the neuronal control of breathing.
AB  - Breathing is controlled by a distributed network involving areas in the
      neocortex, cerebellum, pons, medulla, spinal cord, and various other subcortical
      regions. However, only one area seems to be essential and sufficient for
      generating the respiratory rhythm: the preBotzinger complex (preBotC). Lesioning
      this area abolishes breathing and following isolation in a brain slice the
      preBotC continues to generate different forms of respiratory activities. The use
      of slice preparations led to a thorough understanding of the cellular mechanisms
      that underlie the generation of inspiratory activity within this network. Two
      types of inward currents, the persistent sodium current (I(NaP)) and the calcium
      activated non-specific cation current (I(CAN)), play important roles in
      respiratory rhythm generation. These currents give rise to autonomous pacemaker
      activity within respiratory neurons, leading to the generation of intrinsic
      spiking and bursting activity. These membrane properties amplify as well as
      activate synaptic mechanisms that are critical for the initiation and maintenance
      of inspiratory activity. In this review, we describe the dynamic interplay
      between synaptic and intrinsic membrane properties in the generation of the
      respiratory rhythm and we relate these mechanisms to rhythm generating networks
      involved in other behaviors.

PMID- 22654178
TI  - Inferring and quantifying the role of an intrinsic current in a mechanism for a
      half-center bursting oscillation: A dominant scale and hybrid dynamical systems
      analysis.
AB  - This paper illustrates an informatic technique for inferring and quantifying the
      dynamic role of a single intrinsic current in a mechanism of neural bursting
      activity. We analyze the patterns of the most dominant currents in a model of
      half-center oscillation in the leech heartbeat central pattern generator. We find
      that the patterns of dominance change substantially over a cycle, allowing
      different local reductions to be applied to the model. The result is a hybrid
      dynamical systems model, which is a piecewise representation of the mechanism
      combining multiple vector fields and discrete state changes. The simulation of
      such a model tests explicit hypotheses about the mechanism and is a novel way to
      retain both mathematical clarity and scientific detail in answering mechanistic
      questions about a complex model. Several insights into the central mechanism of
      "escape-release" in the model are elucidated by this analysis and compared with
      previous studies. The broader application and extension of this technique is also
      discussed.

PMID- 22654179
TI  - Qualitative validation of the reduction from two reciprocally coupled neurons to
      one self-coupled neuron in a respiratory network model.
AB  - The pre-Botzinger complex of the mammalian brainstem is a heterogeneous neuronal
      network, and individual neurons within the network have varying strengths of the
      persistent sodium and calcium-activated nonspecific cationic currents.
      Individually, these currents have been the focus of modeling efforts. Previously,
      Dunmyre et al. (J Comput Neurosci 1-24, 2011) proposed a model and studied the
      interactions of these currents within one self-coupled neuron. In this work, I
      consider two identical, reciprocally coupled model neurons and validate the
      reduction to the self-coupled case. I find that all of the dynamics of the two
      model neuron network and the regions of parameter space where these distinct
      dynamics are found are qualitatively preserved in the reduction to the self
      coupled case.

PMID- 22654180
TI  - Positive feedback loops sustain repeating bursts in neuronal circuits.
AB  - Voluntary movements in animals are often episodic, with abrupt onset and
      termination. Elevated neuronal excitation is required to drive the neuronal
      circuits underlying such movements; however, the mechanisms that sustain this
      increased excitation are largely unknown. In the medicinal leech, an identified
      cascade of excitation has been traced from mechanosensory neurons to the swim
      oscillator circuit. Although this cascade explains the initiation of excitatory
      drive (and hence swim initiation), it cannot account for the prolonged excitation
      (10-100 s) that underlies swim episodes. We present results of physiological and
      theoretical investigations into the mechanisms that maintain swimming activity in
      the leech. Although intrasegmental mechanisms can prolong stimulus-evoked
      excitation for more than one second, maintained excitation and sustained swimming
      activity requires chains of several ganglia. Experimental and modeling studies
      suggest that mutually excitatory intersegmental interactions can drive bouts of
      swimming activity in leeches. Our model neuronal circuits, which incorporated
      mutually excitatory neurons whose activity was limited by impulse adaptation,
      also replicated the following major experimental findings: (1) swimming can be
      initiated and terminated by a single neuron, (2) swim duration decreases with
      experimental reduction in nerve cord length, and (3) swim duration decreases as
      the interval between swim episodes is reduced.

PMID- 22654181
TI  - Ion concentration dynamics as a mechanism for neuronal bursting.
AB  - We describe a simple conductance-based model neuron that includes intra- and
      extracellular ion concentration dynamics and show that this model exhibits
      periodic bursting. The bursting arises as the fast-spiking behavior of the neuron
      is modulated by the slow oscillatory behavior in the ion concentration variables
      and vice versa. By separating these time scales and studying the bifurcation
      structure of the neuron, we catalog several qualitatively different bursting
      profiles that are strikingly similar to those seen in experimental preparations.
      Our work suggests that ion concentration dynamics may play an important role in
      modulating neuronal excitability in real biological systems.

PMID- 22654184
TI  - "The times they are a changin:" home diagnosis of sleep apnea has arrived.

PMID- 22654185
TI  - The further rise of internet interventions.

PMID- 22654183
TI  - Sleep: a health imperative.
AB  - Chronic sleep deficiency, defined as a state of inadequate or mistimed sleep, is
      a growing and underappreciated determinant of health status. Sleep deprivation
      contributes to a number of molecular, immune, and neural changes that play a role
      in disease development, independent of primary sleep disorders. These changes in
      biological processes in response to chronic sleep deficiency may serve as
      etiological factors for the development and exacerbation of cardiovascular and
      metabolic diseases and, ultimately, a shortened lifespan. Sleep deprivation also
      results in significant impairments in cognitive and motor performance which
      increase the risk of motor vehicle crashes and work-related injuries and fatal
      accidents. The American Academy of Sleep Medicine and the Sleep Research Society
      have developed this statement to communicate to national health stakeholders the
      current knowledge which ties sufficient sleep and circadian alignment in adults
      to health.

PMID- 22654186
TI  - Searching for genetic clues at the interface of sleep and mood.

PMID- 22654187
TI  - The role of GABA in primary insomnia.

PMID- 22654188
TI  - Respect for muscle.

PMID- 22654189
TI  - The young and the rest-less.

PMID- 22654190
TI  - Early treatment of obstructive apnea and stroke outcome.

PMID- 22654192
TI  - Guidance needed in patient-centered medical home concept for management of
      obstructive sleep apnea.

PMID- 22654194
TI  - The clinical dilema: to treat or not to treat REM related obstructive sleep
      apnea?

PMID- 22654195
TI  - A multisite randomized trial of portable sleep studies and positive airway
      pressure autotitration versus laboratory-based polysomnography for the diagnosis
      and treatment of obstructive sleep apnea: the HomePAP study.
AB  - STUDY OBJECTIVES: To test the utility of an integrated clinical pathway for
      obstructive sleep apnea (OSA) diagnosis and continuous positive airway pressure
      (CPAP) treatment using portable monitoring devices. DESIGN: Randomized, open
      label, parallel group, unblinded, multicenter clinical trial comparing home
      based, unattended portable monitoring for diagnosis and autotitrating CPAP
      (autoPAP) compared with in-laboratory polysomnography (PSG) and CPAP titration.
      SETTING: Seven American Academy of Sleep Medicine (AASM) accredited sleep
      centers. PARTICIPANTS: Consecutive new referrals, age 18 yr or older with high
      probability of moderate to severe OSA (apnea-hypopnea index [AHI] >= 15)
      identified by clinical algorithm and Epworth Sleepiness Scale (ESS) score >= 12.
      INTERVENTIONS: Home-based level 3 testing followed by 1 wk of autoPAP with a
      fixed pressure CPAP prescription based on the 90% pressure from autotitration of
      PAP therapy (autoPAP) device (HOME) compared with attended, in-laboratory studies
      (LAB). MEASUREMENTS: CPAP acceptance, time to treatment, adherence at 1 and 3 mo;
      changes in ESS, and functional outcomes. RESULTS: Of 373 participants,
      approximately one-half in each study arm remained eligible (AHI >= 15) to
      continue in the study. At 3 mo, PAP usage (nightly time at pressure) was 1 hr
      greater: 4.7 +/- 2.1 hr (HOME) compared with 3.7 +/- 2.4 hr (LAB). Adherence
      (percentage of night used >= 4 hr) was 12.6% higher: 62.8 +/- 29.2% compared with
      49.4 +/- 36.1% in the HOME versus LAB. Acceptance of PAP therapy, titration
      pressures, effective titrations, time to treatment, and ESS score change did not
      differ between arms. CONCLUSIONS: A home-based strategy for diagnosis and
      treatment compared with in-laboratory PSG was not inferior in terms of
      acceptance, adherence, time to treatment, and functional improvements. TRIAL
      REGISTRATION: http://www.ClinicalTrials.gov; Identifier: NCT: 00642486.

PMID- 22654196
TI  - A randomized, placebo-controlled trial of online cognitive behavioral therapy for
      chronic insomnia disorder delivered via an automated media-rich web application.
AB  - STUDY OBJECTIVES: The internet provides a pervasive milieu for healthcare
      delivery. The purpose of this study was to determine the effectiveness of a novel
      web-based cognitive behavioral therapy (CBT) course delivered by an automated
      virtual therapist, when compared with a credible placebo; an approach required
      because web products may be intrinsically engaging, and vulnerable to placebo
      response. DESIGN: Randomized, placebo-controlled trial comprising 3 arms: CBT,
      imagery relief therapy (IRT: placebo), treatment as usual (TAU). SETTING: Online
      community of participants in the UK. PARTICIPANTS: One hundred sixty-four adults
      (120 F: [mean age 49y (18-78y)] meeting proposed DSM-5 criteria for Insomnia
      Disorder, randomly assigned to CBT (n = 55; 40 F), IRT placebo (n = 55; 42 F) or
      TAU (n = 54; 38 F). INTERVENTIONS: CBT and IRT each comprised 6 online sessions
      delivered by an animated personal therapist, with automated web and email
      support. Participants also had access to a video library/back catalogue of
      session content and Wikipedia style articles. Online CBT users had access to a
      moderated social network/community of users. TAU comprised no restrictions on
      usual care and access to an online sleep diary. MEASUREMENTS AND RESULTS: Major
      assessments at baseline, post-treatment, and at follow-up 8-weeks post-treatment;
      outcomes appraised by online sleep diaries and clinical status. On the primary
      endpoint of sleep efficiency (SE; total time asleep expressed as a percentage of
      the total time spent in bed), online CBT was associated with sustained
      improvement at post-treatment (+20%) relative to both TAU (+6%; d = 0.95) and IRT
      (+6%: d = 1.06), and at 8 weeks (+20%) relative to IRT (+7%: d = 1.00) and TAU
      (+9%: d = 0.69) These findings were mirrored across a range of sleep diary
      measures. Clinical benefits of CBT were evidenced by modest superiority over
      placebo on daytime outcomes (d = 0.23-0.37) and by substantial improved sleep
      wake functioning on the Sleep Condition Indicator (range of d = 0.77-1.20). Three
      quarters of CBT participants (76% [CBT] vs. 29% [IRT] and 18% [TAU]) completed
      treatment with SE > 80%, more than half (55% [CBT] vs. 17% [IRT] and 8% [TAU])
      with SE > 85%, and over one-third (38% [CBT] vs. 6% [IRT] and 0% [TAU]) with SE >
      90%; these improvements were largely maintained during follow-up. CONCLUSION: CBT
      delivered using a media-rich web application with automated support and a
      community forum is effective in improving the sleep and associated daytime
      functioning of adults with insomnia disorder. CLINICAL TRIAL REGISTRATION: ISRCTN
      - 44615689.

PMID- 22654197
TI  - Sleep is associated with the metabolic syndrome in a multi-ethnic cohort of
      midlife women: the SWAN Sleep Study.
AB  - STUDY OBJECTIVES: We evaluated associations among subjective and objective
      measures of sleep and the metabolic syndrome in a multi-ethnic sample of midlife
      women. DESIGN: Cross-sectional study. SETTING: Participants' homes. PARTICIPANTS:
      Caucasian (n = 158), African American (n = 125), and Chinese women (n = 57); mean
      age = 51 years. Age range = 46-57 years. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: Metabolic syndrome was measured in the clinic and sleep quality was
      assessed by self-report. Indices of sleep duration, continuity/fragmentation,
      depth, and sleep disordered breathing were assessed by in-home polysomnography
      (PSG). Covariates included sociodemographics, menopausal status, use of
      medications that affect sleep, and self-reported health complaints and health
      behaviors known to influence metabolic syndrome risk. Logistic regression was
      used to test the hypothesis that the metabolic syndrome would be associated with
      increased subjective sleep complaints and PSG-assessed sleep disturbances. In
      univariate analyses, the metabolic syndrome was associated with decreased sleep
      duration and efficiency and increased NREM beta power and apnea-hypopnea index
      (AHI). After covariate adjustment, sleep efficiency (odds ratio [OR] = 2.06, 95%
      confidence interval [CI]: 1.08-3.93), NREM beta power (OR = 2.09, 95% CI: 1.09
      3.98), and AHI (OR = 1.86, 95% CI: 1.40-2.48) remained significantly associated
      with the metabolic syndrome (odds ratio values are expressed in standard
      deviation units). These relationships did not differ by race. CONCLUSIONS:
      Objective indices of sleep continuity, depth, and sleep disordered breathing are
      significant correlates of the metabolic syndrome in midlife women, independent of
      race, menopausal status and other factors that might otherwise account for these
      relationships.

PMID- 22654198
TI  - Short sleep as an environmental exposure: a preliminary study associating 5
      HTTLPR genotype to self-reported sleep duration and depressed mood in first-year
      university students.
AB  - OBJECTIVES: This study examined whether the 5-HTTLPR polymorphism in the SLC6A4
      gene is associated with self-reported symptoms of depressed mood in first-year
      university students with a persistent pattern of short sleep. DESIGN: Students
      provided DNA samples and completed on-line sleep diaries and a mood scale during
      the first semester. A priori phenotypes for nocturnal sleep and mood scores were
      compared for the distribution of genotypes. SETTING: Brown University,
      Providence, Rhode Island. PARTICIPANTS: A sample of 135 first-year students, 54
      male, 71 Caucasian, mean age 18.1 (+/- 0.5) yr. INTERVENTIONS: None.
      MEASUREMENTS: Students completed on-line sleep diaries daily across the first
      term (21-64 days; mean = 51 days +/- 11) and Center for Epidemiologic Studies
      Depression (CES-D) mood scale after 8 wk. DNA was genotyped for the triallelic 5
      HTTLPR polymorphism. Low-expressing S and L(G)polymorphisms were designated S',
      and high-expressing L(A) was designated L'. Phenotype groups were identified from
      a combination of CES-D (median split: high > 12; low < 13) and mean nocturnal
      total sleep time (TST) from diaries: (shorter <= 7 hr; longer >= 7.5 hr). Three
      genotypes were identified (S'S', S'L', L'L'); the S'S' genotype was present in a
      higher proportion of Asian than non-Asian students. RESULTS: FOUR PHENOTYPE
      GROUPS WERE COMPARED: 40 students with shorter TST/high CES-D; 34 with shorter
      TST/low CES-D; 29 with longer TST/high CES-D; 32 with longer TST/low CES-D.
      Female:male distribution did not vary across phenotype groups (chi-square = 1.39;
      df = 3; P = 0.71). S'S' participants (n = 23) were overrepresented in the shorter
      TST/high CES-D group (chi- square = 15.04; df = 6; P < 0.02). This association
      was sustained after removing participants with preexisting evidence of depressed
      mood (chi-square = 12.90; df = 6; P = 0.045). CONCLUSION: These data indicate
      that young adults who reported shorter nocturnal sleep and higher depressed mood
      are more likely than others to carry a variant of the SLC6A4 gene associated with
      low expression of the serotonin transporter.

PMID- 22654199
TI  - Dismantling multicomponent behavioral treatment for insomnia in older adults: a
      randomized controlled trial.
AB  - STUDY OBJECTIVE: Recently, the use of multicomponent insomnia treatment has
      increased. This study compares the effect of single component and multicomponent
      behavioral treatments for insomnia in older adults after intervention and at 3
      months and 1 yr posttreatment. DESIGN: A randomized, controlled study. SETTING:
      Veterans Affairs medical center. PARTICIPANTS: 179 older adults (mean age, 68.9
      yr +/- 8.0; 115 women [64.2%]) with chronic primary insomnia. INTERVENTIONS:
      Participants were randomly assigned to 6 wk of stimulus control therapy (SCT),
      sleep restriction therapy (SRT), the 2 therapies combined into a multicomponent
      intervention (MCI), or a wait-list control group. MEASUREMENTS AND RESULTS:
      Primary outcomes were subjective (daily sleep diary) and objective (actigraphy)
      measures of sleep-onset latency (SOL), wake after sleep onset (WASO), total sleep
      time (TST), time in bed (TIB), and sleep efficiency (SE). Secondary outcomes were
      clinical measures including response and remission rates. There were no
      differences between the single and multicomponent interventions on primary sleep
      outcomes measured by diary and actigraphy. All treatments produced significant
      improvement in diary-reported sleep in comparison with the control group. Effect
      sizes for sleep diary outcomes were medium to large. Treatment gains were
      maintained at follow-up for diary and actigraph measured SOL, WASO, and SE. The
      MCI group had the largest proportion of treatment remitters. CONCLUSIONS: For
      older adults with chronic primary insomnia, the findings provide initial evidence
      that SCT, SRT, and MCI are equally efficacious and produce sustainable treatment
      gains on diary, actigraphy, and clinical outcomes. From a clinical perspective,
      MCI may be a preferred treatment due to its higher remission rate. CLINICAL TRIAL
      INFORMATION: Behavioral Intervention for Insomnia in Older Adults. NCT01154023.
      URL:
      http://clinicaltrials.gov/ct2/show/NCT01154023?term=Behavioral+Intervention+for+I
      somnia+in+Older+Adults&rank=1.

PMID- 22654200
TI  - Cortical GABA levels in primary insomnia.
AB  - STUDY OBJECTIVES: GABA is increasingly recognized as an important
      neurotransmitter for the initiation and maintenance of sleep. We sought to
      measure cortical GABA content through proton magnetic resonance spectroscopy
      (MRS) in persons with and without primary insomnia, and relate brain GABA levels
      to polysomnographic sleep measures. DESIGN: Two-group comparison study. SETTING:
      Outpatient study at a university research clinic. PARTICIPANTS: Non-medicated
      persons with primary insomnia (N = 16) and no sleep complaints (N = 17).
      INTERVENTIONS: Participants kept sleep diaries and a regular time-in-bed schedule
      for 9 days, culminating in 2 consecutive nights of ambulatory polysomnography and
      a single proton MRS session. The main outcome measure was occipital GABA/creatine
      ratios; secondary measures included sleep measurements and relationship between
      polysomnographically measured time awake after sleep onset and occipital GABA
      content. MEASUREMENTS AND RESULTS: The primary insomnia group was distinguished
      from persons with no sleep complaints on self-reported and polysomnographically
      measured sleep. The two groups did not differ in age, sex, body mass index,
      habitual bed- and wake-times, napping, use of caffeine, or use of cigarettes.
      Mean occipital GABA level was 12% higher in persons with insomnia than in persons
      without sleep complaints (P < 0.05). In both groups, GABA levels correlated
      negatively with polysomnographically measured time awake after sleep onset (P <
      0.05). CONCLUSIONS: Increased GABA levels in persons with insomnia may reflect an
      allostatic response to chronic hyperarousal. The preserved, negative relationship
      between GABA and time awake after sleep onset supports this notion, indicating
      that the possible allostatic response is adaptive.

PMID- 22654201
TI  - The longitudinal course of insomnia symptoms: inequalities by sex and
      occupational class among two different age cohorts followed for 20 years in the
      west of Scotland.
AB  - STUDY OBJECTIVES: The natural history of insomnia symptomatology is poorly
      understood. Cross-sectional associations have been demonstrated among
      socioeconomic disadvantage, female sex, and poor sleep but it is unclear how
      these social factors predict patterns of insomnia symptoms over time. The aim of
      this article is to describe longitudinal patterns of insomnia symptoms as people
      age and investigate how they vary by sex and occupational class. DESIGN: A
      prospective cohort study with 20 yr of follow-up from 1987 to 1988. SETTING: West
      of Scotland. PARTICIPANTS: One cohort approximately 36 yr of age at baseline
      aging to 57 yr (n = 1,444), and another aging from approximately 56 to 76 yr (n =
      1,551). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: At approximately 5-yr
      intervals, respondents self-reported trouble initiating and maintaining sleep.
      Latent class analysis identified 4 main sleep patterns: a healthy pattern with
      little sleeping trouble across the 20 yr; an episodic pattern, characterized by
      trouble maintaining sleep; a chronic pattern with trouble maintaining and
      initiating sleep throughout the study; and a pattern where symptoms developed
      during the 20-yr follow-up. Chronic patterns were more likely in the older cohort
      than the younger one, for women than men in the older cohort, and for those from
      a manual rather than a nonmanual occupational class in both cohorts. In the
      middle-aged cohort a developing pattern was more likely for women than men.
      CONCLUSIONS: Chronic symptoms, characterized by both trouble maintaining and
      initiating sleep, are patterned by social factors.

PMID- 22654202
TI  - Insomnia, comorbidity, and risk of injury among insured Americans: results from
      the America Insomnia Survey.
AB  - STUDY OBJECTIVES: To estimate associations of broadly defined insomnia (i.e.,
      meeting inclusion criteria for International Classification of Diseases, Tenth
      Revision (ICD-10), Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition (DSM-IV), or Research Diagnostic Criteria/International Classification of
      Sleep Disorders, Second Edition (RDC/ICSD-2) diagnosis) with
      workplace/nonworkplace injuries controlling for comorbid conditions among workers
      in the America Insomnia Survey (AIS). DESIGN/SETTING: Cross-sectional telephone
      survey. PARTICIPANTS: National sample of 4,991 employed health plan subscribers
      (age 18 yr and older). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Broadly
      defined insomnia with duration of at least 12 mo was assessed with the Brief
      Insomnia Questionnaire (BIQ). Injuries in the 12 mo before interview were
      assessed with a standard self-report measure of injuries causing role impairment
      or requiring medical attention. Eighteen comorbid condition clusters were
      assessed with medical/pharmacy claims records and self-reports. Insomnia had
      significant gross associations (odds ratios, ORs) with both workplace and
      nonworkplace injuries (OR 2.0 and 1.5, respectively) in logistic regression
      analyses before controlling for comorbid conditions. The significant population
      attributable risk proportions (PARPs) of total injuries with insomnia was 4.6%
      after controlling for comorbid conditions. Only 2 other conditions had PARPs
      exceeding those of insomnia. The associations of insomnia with injuries did not
      vary significantly with worker age, sex, or education, but did vary significantly
      with comorbid conditions. Specifically, insomnia was significantly associated
      with workplace and nonworkplace injuries (OR 1.8 and 1.5, respectively) among
      workers having no comorbid conditions, with workplace but not nonworkplace
      injuries (OR 1.8 and 1.2, respectively) among workers having 1 comorbid
      condition, and with neither workplace nor nonworkplace injuries (OR 0.9 and 1.0,
      respectively) among workers having 2 or more comorbid conditions. CONCLUSIONS:
      The associations of insomnia with injuries vary with comorbid conditions in ways
      that could have important implications for targeting workplace interventions.

PMID- 22654203
TI  - Normative EMG values during REM sleep for the diagnosis of REM sleep behavior
      disorder.
AB  - BACKGROUND: Correct diagnosis of rapid eye movement sleep behavior disorder (RBD)
      is important because it can be the first manifestation of a neurodegenerative
      disease, it may lead to serious injury, and it is a well-treatable disorder. We
      evaluated the electromyographic (EMG) activity in the Sleep Innsbruck Barcelona
      (SINBAR) montage (mentalis, flexor digitorum superficialis, extensor digitorum
      brevis) and other muscles to obtain normative values for the correct diagnosis of
      RBD for clinical practice. SETTING: Two university hospital sleep disorder
      centers. PARTICIPANTS: Thirty RBD patients (15 idiopathic [iRBD], 15 with
      Parkinson disease [PD]) and 30 matched controls recruited from patients with
      effectively treated sleep related breathing disorders. INTERVENTIONS: Not
      applicable. METHODS AND RESULTS: Participants underwent video-polysomnography,
      including registration of 11 body muscles. Tonic, phasic, and "any" (any type of
      EMG activity, irrespective of whether it consisted of tonic, phasic or a
      combination of both) EMG activity was blindly quantified for each muscle. When
      choosing a specificity of 100%, the 3-sec miniepoch cutoff for a diagnosis of RBD
      was 18% for "any" EMG activity in the mentalis muscle (area under the curve [AUC]
      0.990). Discriminative power was higher in upper limb (100% specificity, AUC
      0.987-9.997) than in lower limb muscles (100% specificity, AUC 0.813-0.852). The
      combination of "any" EMG activity in the mentalis muscle with both phasic flexor
      digitorum superficialis muscles yielded a cutoff of 32% (AUC 0.998) for patients
      with iRBD and with PD-RBD. CONCLUSION: For the diagnosis of iRBD and RBD
      associated with PD, we recommend a polysomnographic montage quantifying "any"
      (any type of EMG activity, irrespective of whether it consisted of tonic, phasic
      or a combination of both) EMG activity in the mentalis muscle and phasic EMG
      activity in the right and left flexor digitorum superficialis muscles in the
      upper limbs with a cutoff of 32%, when using 3-sec miniepochs.

PMID- 22654204
TI  - Repeated sleep restriction in adolescent rats altered sleep patterns and impaired
      spatial learning/memory ability.
AB  - STUDY OBJECTIVES: To investigate possible differences in the effect of repeated
      sleep restriction (RSR) during adolescence and adulthood on sleep homeostasis and
      spatial learning and memory ability. DESIGN: The authors examined
      electroencephalograms of rats as they were subjected to 4-h daily sleep
      deprivation that continued for 7 consecutive days and assessed the spatial
      learning and memory by Morris water maze test (WMT). PARTICIPANTS: Adolescent and
      adult rats. MEASUREMENTS AND RESULTS: Adolescent rats exhibited a similar amount
      of rapid eye movement (REM) and nonrapid eye movement (NREM) sleep with higher
      slow wave activity (SWA, 0.5-4 Hz) and fewer episodes and conversions with
      prolonged durations, indicating they have better sleep quality than adult rats.
      After RSR, adult rats showed strong rebound of REM sleep by 31% on sleep
      deprivation day 1; this value was 37% on sleep deprivation day 7 in adolescents
      compared with 20-h baseline level. On sleep deprivation day 7, SWA in adult and
      adolescent rats increased by 47% and 33%, and such elevation lasted for 5 h and 7
      h, respectively. Furthermore, the authors investigated the effects of 4-h daily
      sleep deprivation immediately after the water maze training sessions on spatial
      cognitive performance. Adolescent rats sleep-restricted for 7 days traveled a
      longer distance to find the hidden platform during the acquisition training and
      had fewer numbers of platform crossings in the probe trial than those in the
      control group, something that did not occur in the sleep-deprived adult rats.
      CONCLUSIONS: Repeated sleep restriction (RSR) altered sleep profiles and mildly
      impaired spatial learning and memory capability in adolescent rats.

PMID- 22654205
TI  - Decoupling of sleepiness from sleep time and intensity during chronic sleep
      restriction: evidence for a role of the adenosine system.
AB  - STUDY OBJECTIVE: Sleep responses to chronic sleep restriction (CSR) might be very
      different from those observed after short-term total sleep deprivation. For
      example, after sleep restriction continues for several consecutive days, animals
      no longer express compensatory increases in daily sleep time and sleep intensity.
      However, it is unknown if these allostatic, or adaptive, sleep responses to CSR
      are paralleled by behavioral and neurochemical measures of sleepiness. DESIGN:
      This study was designed to investigate CSR-induced changes in (1) sleep time and
      intensity as a measure of electrophysiological sleepiness, (2) sleep latency as a
      measure of behavioral sleepiness, and (3) brain adenosine A1 (A1R) and A2a
      receptor (A2aR) mRNA levels as a putative neurochemical correlate of sleepiness.
      SUBJECTS: Male Sprague-Dawley rats INTERVENTIONS: A 5-day sleep restriction (SR)
      protocol consisting of 18-h sleep deprivation and 6-h sleep opportunity each day.
      MEASUREMENT AND RESULTS: Unlike the first SR day, rats did not sleep longer or
      deeper on days 2 through 5, even though they exhibited significant elevations of
      behavioral sleepiness throughout all 5 SR days. For all SR days and recovery day
      1, A1R mRNA in the basal forebrain was maintained at elevated levels, whereas
      A2aR mRNA in the frontal cortex was maintained at reduced levels. CONCLUSION: CSR
      LEADS TO A DECOUPLING OF SLEEPINESS FROM SLEEP TIME AND SLEEP INTENSITY,
      SUGGESTING THAT THERE ARE AT LEAST TWO DIFFERENT SLEEP REGULATORY SYSTEMS: one
      mediating sleepiness (homeostatic) and the other mediating sleep time/intensity
      (allostatic). The time course of changes observed in adenosine receptor mRNA
      levels suggests that the basal forebrain and cortical adenosine system might
      mediate sleepiness rather than sleep time or intensity.

PMID- 22654206
TI  - The effects of a nighttime nap on the error-monitoring functions during extended
      wakefulness.
AB  - STUDY OBJECTIVES: To examine the effects of a 1-hr nighttime nap, and the
      associated sleep inertia, on the error-monitoring functions during extended
      wakefulness using the 2 event-related potential components thought to reflect
      error detection and emotional or motivational evaluation of the error, i.e., the
      error-related negativity/error-negativity (ERN/Ne) and error-positivity (Pe),
      respectively. DESIGN: Participants awakened at 07:00 the morning of the
      experimental day, and performed a stimulus-response compatibility (arrow
      orientation) task at 21:00, 02:00, and 03:00. SETTING: A cognitive task with EEG
      data recording was performed in a laboratory setting. PARTICIPANTS: Twenty young
      adults (mean age 21.3 +/- 1.0 yr, 14 males) participated. INTERVENTIONS: Half of
      the participants took a 1-hr nap, and the others had a 1-hr awake-rest period
      from 01:00-02:00. MEASUREMENTS AND RESULTS: Behavioral performance and amplitude
      of the Pe declined after midnight (i.e., 02:00 and 03:00) compared with the 21:00
      task period in both groups. During the task period starting at 03:00, the
      participants in the awake-rest condition reported less alertness and showed fewer
      correct responses than those who napped. However, there were no effects of a nap
      on the amplitude of the ERN/Ne or Pe. CONCLUSIONS: Our results suggest that a 1
      hr nap can alleviate the decline in subjective alertness and response accuracy
      during nighttime; however, error-monitoring functions, especially emotional or
      motivational evaluation of the error, might remain impaired by extended
      wakefulness even after the nap. This phenomenon could imply that night-shift
      workers experiencing extended wakefulness should not overestimate the positive
      effects of a nighttime 1-hr nap during extended wakefulness.

PMID- 22654209
TI  - Antiretrovirals and the use of traditional, complementary and alternative
      medicine by HIV patients in Kwazulu-Natal, South Africa: a longitudinal study.
AB  - The aim of this prospective study (20 months) was to assess HIV patients' use of
      Traditional, Complementary and Alternative Medicine (TCAM) and its effect on ARV
      adherence at three public hospitals in KwaZulu-Natal, South Africa. Seven hundred
      and thirty-five (29.8% male and 70.2% female) patients who consecutively attended
      three HIV clinics completed assessments prior to ARV initiation, 519 after 6
      months, 557 after 12 and 499 after 20 months on antiretroviral therapy (ART).
      Results indicate that following initiation of ARV therapy the use of herbal
      therapies for HIV declined significantly from 36.6% prior to ARV therapy to 8.0%
      after 6 months, 4.1% after 12 months and 0.6% after 20 months on ARVs. Faith
      healing methods (including spiritual practices and prayer) declined from 35.8% to
      22.1%, 20.8% and 15.5%, respectively. In contrast, the use of micronutrients
      (vitamins, etc.) significantly increased from 42.6% to 78.2%. The major herbal
      remedies that were used prior to ART were unnamed traditional medicine, followed
      by imbiza (Scilla natalensis planch), canova (immune booster), izifozonke
      (essential vitamins mixed with herbs), African potato (Hypoxis hemerocallidea),
      stametta (aloe mixed with vitamins and herbs) and ingwe (tonic). Herbal remedies
      were mainly used for pain relief, as immune booster and for stopping diarrhea. As
      herbal treatment for HIV was associated with reduced ARV adherence, patient's use
      of TCAM should be considered in ARV adherence management.

PMID- 22654210
TI  - Disclosure of the quackery: testing of the bactericidal action of products based
      on the "hydronic" technology ("informed glass") on ATCC strains of Enterococcus
      faecalis, Salmonella enteritidis and Candida albicans.
AB  - To disclose a quackery called "revitalisation of tired water by hydronic
      technology", scientific experiments have been conducted with drinking water kept
      in "ordinary, everyday-use" drinking glasses and so-called 'informed' glasses, a
      patent-protected product supposed to have an effect on the "structure, vitality
      and memory of water". Drinking "informed" water is claimed to have a wide range
      of positive revitalising health effects (blue informed glass), to facilitate
      weight loss (red informed glass) and to have a stress-relieving action (green
      informed glass). Allegedly, by the use of the "orgon methodology", information is
      coded into the glass, which action is additionally enforced by the addition of
      the "magic life" symbol - a specially designed energy condenser which, together
      with the selected information, is permanently introduced into the liquid
      contained in the glass. Since the manufacturer claimed the products to have a
      broad bactericidal action, regardless of the external conditions and completely
      independent from additional factor that would lead to the activation of the
      system, the efficacy of the informed drinking glass was tested using
      standardised, microbiological tests. Respecting the principle of a single-blind
      test for each of 5 samples of each type of the informed glass, growth reduction
      factor (RF) (difference log cfu/ml - colony per unit/ml of control glass and log
      cfu/ml of each informed glass) was determined after 0,2,4,6 and 8 h in spring
      water experimentally contaminated with standardised ATCC strains of two types of
      bacteria and one yeast. The results showed a statistically significant
      bactericidal action of the blue informed glass with all strains-Enterococcus
      faecalis (RF 0.62/0.76), Salmonella enteritidis (RF 0.87/0.97), and Candida
      albicans (RF 0.5/0.60) - as opposed to the red and green glasses where this
      effect was negligible (RF < 0.1). However, when the tests were repeated in
      complete darkness, none of the three informed glasses showed any bactericidal
      action. The obtained results indicate a fraud: bactericidal effect is rather a
      result of photocatalytic action of a hidden component used on purpose in the
      production of glass or subsequently applied by the use of nanotechnology
      (possibly antimony trioxide or titanium oxide) than of the so-called "orgon and
      hydronic technology".

PMID- 22654207
TI  - Telemetric study of sleep architecture and sleep homeostasis in the day-active
      tree shrew Tupaia belangeri.
AB  - STUDY OBJECTIVES: In this study the authors characterized sleep architecture and
      sleep homeostasis in the tree shrew, Tupaia belangeri, a small, omnivorous, day
      active mammal that is closely related to primates. DESIGN: Adult tree shrews were
      individually housed under a 12-hr light/12-hr dark cycle in large cages
      containing tree branches and a nest box. The animals were equipped with radio
      transmitters to allow continuous recording of electroencephalogram (EEG),
      electromyogram (EMG), and body temperature without restricting their movements.
      Recordings were performed under baseline conditions and after sleep deprivation
      (SD) for 6 hr or 12 hr during the dark phase. MEASUREMENTS AND RESULTS: Under
      baseline conditions, the tree shrews spent a total of 62.4 +/- 1.4% of the 24-hr
      cycle asleep, with 91.2 +/- 0.7% of sleep during the dark phase and 33.7 +/- 2.8%
      sleep during the light phase. During the dark phase, all sleep occurred in the
      nest box; 79.6% of it was non-rapid eye movement (NREM) sleep and 20.4% was rapid
      eye movement (REM) sleep. In contrast, during the light phase, sleep occurred
      almost exclusively on the top branches of the cage and only consisted of NREM
      sleep. SD was followed by an immediate increase in NREM sleep time and an
      increase in NREM sleep EEG slow-wave activity (SWA), indicating increased sleep
      intensity. The cumulative increase in NREM sleep time and intensity almost made
      up for the NREM sleep that had been lost during 6-hr SD, but did not fully make
      up for the NREM sleep lost during 12-hr SD. Also, only a small fraction of the
      REM sleep that was lost was recovered, which mainly occurred on the second
      recovery night. CONCLUSIONS: The day-active tree shrew shares most of the
      characteristics of sleep structure and sleep homeostasis that have been reported
      for other mammalian species, with some peculiarities. Because the tree shrew is
      an established laboratory animal in neurobiological research, it may be a
      valuable model species for studies of sleep regulation and sleep function, with
      the added advantage that it is a day-active species closely related to primates.

PMID- 22654211
TI  - Combination of acupuncture and chinese medicinal herbs in treating model rats
      with polycystic ovary syndrome.
AB  - We explored the effects of combination of acupuncture and Chinese medicinal herbs
      in treating model rats with polycystic ovarian syndrome (PCOS) and to explore
      whether acupuncture has positive effects on the absorption of salvianolic acid B
      in the extracts of a Chinese medicine formula when treating the model rats. 60
      female Sprague-Dawley (SD) rats were randomly divided into Groups A, B, C, D, E
      and F, with ten rats in each group. Except Group F, all of the other rats were
      induced to PCOS with oral administration of letrozole. The rats in Group F served
      as normal controls. Group A was treated with acupuncture. Group B was treated
      with oral administration of the extracts of the Chinese medicine formula. Group C
      was treated with a combination of oral administration of the extracts of Chinese
      medicine and acupuncture. Group D received western medicine as positive controls.
      After treatment, the serum levels of follicle stimulating hormone (FSH),
      luteinizing hormone(LH) and testosterone (T) in each group were detected with the
      Enzyme-Linked ImmunoSorbent Assay (ELISA) and the serum concentration of
      salvianolic acid B were determined using High Performance Liquid Chromatography
      (HPLC). The serum levels of T and the ratio of LH/FSH in Group A, B. C, D, and F
      were significantly lower than those of Group E, indicating the model rats with
      PCOS were successfully established. Compared with Groups A, B, D and E, the serum
      levels of T and the ratio of LH/FSH in Group C were significantly lower
      respectively, indicating combination of acupuncture and Chinese medicinal herbs
      can significantly enhance curative effects in treating model rats with PCOS. The
      concentration of serum salvianolic acid Group C was significantly higher than
      Group B, indicating that acupuncture might improve the absorption of salvianolic
      acid B from the extracts of Salvia miltiorrhiza Bunge in the Chinese medicine
      formula. Combination of acupuncture and Chinese medicinal herbs significantly
      enhance curative effects in treating model rats with PCOS and acupuncture has
      positive effects in improving the absorption of salvianolic acid B in the
      extracts of the Chinese medicine formula when treating the model rats with PCOS.

PMID- 22654212
TI  - Antioxidant capacity of some plant foods and beverages consumed in the Eastern
      Region of Nigeria.
AB  - Today plant foods and beverages are receiving more scientific attention because
      of their potential to curb the effect of free radicals in the human system. The
      present study reports on the antioxidant potentials of some plants foods and
      beverages consumed in the Eastern Region of Nigeria. The study made use of the
      ferric reducing antioxidant power, phenolic and the flavonoid contents assays to
      assess the quality of the antioxidant potentials of the plant foods and
      beverages. Of the different classes of foods analyzed the following showed high
      antioxidant potentials: coffee for beverages, star apple for fruits, thyme for
      vegetable and spices, and raices for alcoholic beverages. Generally the
      vegetables and spices registered the highest antioxidant properties. The results
      obtained in this study could help consumers' choice based on the antioxidant
      capacity of the samples analyzed.

PMID- 22654213
TI  - Structure, control and regulation of the formal market for medicinal plants'
      products in Nigeria.
AB  - There are informal and formal markets for medicinal plants' products in Nigeria.
      The formal market is subject to the national regulatory framework for Food and
      Drug Administration and Control. It is relatively new and underdeveloped. This
      study was designed to appraise this market with special emphasis on the market
      participants, market structure, marketing functions performed, conduct of sellers
      in the market and; standards and regulations to which the market is subject.
      Information used for this study was collected through personal interviews and
      interactions with key participants in the market; especially the officials of
      regulatory agency. The market structure was analysed in terms of the share of
      market controlled by participants and product types. Concentration Ratios (CR2
      and CR4) were used to assess the market share. Marketing functions being
      performed were described in terms of the exchange, physical and facilitating
      functions while the conduct was described in terms of pricing and promotional
      strategies. The regulatory framework under which the market operates was
      appraised. The market was highly concentrated with a CR2 and CR4 of 58.5% and
      80.8 %; respectively. Imported products accounted for only 12.3% of the market.
      The predominant modes of presentation of the product were capsule (41.6%) and
      liquid (36.2%). About 20.77% of the products were classified as multivitamins,
      13.85% were antibiotics while 10.77% addressed sexual dysfunctional problems.
      These products were regulated under the Food and Drug Administration and Control
      (NAFDAC) decrees, 1993-1999. Only 2.3% of the products have received full
      registration status while the others were only listed.

PMID- 22654214
TI  - Myostimulating effect of sesamum radiatum aqueous leaf extract in isolated Guinea
      pig Taenia caeci contractile activity.
AB  - This study was carried to examine the effects of the aqueous leaf extract of
      Sesamum radiatum, a laxative plant on the contractile activity of Taenia caeci,
      an intestinal smooth muscle. Strips of Taenia caeci were rapidly removed from
      guinea-pig and were suspended between two L-shaped stainless steel hooks in a 10
      ml organ bath with Mac Ewen solution. The isometric contractile force of the
      Taenia caeci strips were recorded by using a strain gauge. S. radiatum aqueous
      leaf extract (ESera) is a spasmogenic substance. This myostimulant effect is
      characterized by the increase of the rhythm and the amplitude of isolated guinea
      pig Taenia caeci smooth muscle in normal solution and by the development of
      contracture in modified solution and in solution without calcium. A similar
      effect was observed with ACh which caused a graded increase of the contractile
      activity of Taenia caeci. The effects induced by ESera and ACh were reversed in
      the presence of atropine. The spasmogenic effect induced by ESera could justify
      partially the use of S. radiatum as laxative in traditional medicine.

PMID- 22654215
TI  - Preliminary phytochemical screening and antimicrobial evaluation of three
      medicinal plants used in Nigeria.
AB  - Methanol extract of three Nigerian medicinal plants were screened for
      antimicrobial activity using modified Kirby-Bauer disc diffusion and agar
      dilution techniques to determine the diameters of zone of inhibition and minimum
      inhibitory concentrations (MIC) of the extracts respectively. The extract of each
      of the plants were tested against five clinical bacterial isolates comprising of
      two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and
      three Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli and
      Klebsiella pneumonia) organisms. All the extracts exhibited moderate to high
      level of antimicrobial activities against these microorganisms. Phytochemical
      screening of powdered plant material revealed the presence of some secondary
      metabolites such as alkaloids, saponins, tannins, anthraquinones and flavonoids.
      These Nigerian medicinal plants could be developed into cheap, safe and
      culturally acceptable standardized herbal products and may serve as a source of
      new molecules for broad-spectrum antimicrobial agents.

PMID- 22654216
TI  - In vitro antioxidant activity of extracts from the leaves of Abies pindrow Royle.
AB  - Traditionally, the leaves of Abies pindrow Royle are employed as an ayurvedic
      remedy for fever, hypoglycaemic, respiratory and inflammatory conditions. In this
      study, dichloromethane, methanol and acetone extracts of A. pindrow leaves were
      analysed for their phytochemical content and in vitro antioxidant activities. The
      methanol extract exhibited highest antioxidant activity while acetone extract
      showed presence of relatively high total phenol and flavonoids contents. The
      present study provides evidence that extracts of Abies pindrow leaves are a
      potential source of natural antioxidants and could serve as a base for future
      drugs.

PMID- 22654217
TI  - Management of experimental benign prostatic hyperplasia in rats using a food
      based therapy containing Telfairia occidentalis seeds.
AB  - The usefulness of diet containing Telfairia occidentalis seeds, in managing
      benign prostatic hyperplasia (BPH) in rats was studied. Twenty male Wistar rats
      were divided into four equal groups. BPH was induced by sub-cutaneous injection
      of dihydrotestosterone (DHT) and estradiol valerate (ratio, 10:1) every other day
      for 28 days. Rats in the test group were placed on the test diet for 7 days
      following disease induction. One control group (DC) was fed on a normal diet for
      7 days following disease induction. Two other control groups, HC and HDC, were
      given sub-cutaneous olive oil (vehicle) for the same duration, and placed on the
      test diet and normal diet, respectively. Markers of BPH, and hormone profile were
      determined using standard methods. The results show that relative prostate weight
      and protein content of the prostates were lower [albeit not significantly
      (p>0.05)] in the test group, relative to the DC group. Serum prostatic acid
      phosphatase concentrations (U/L) decreased significantly (p<0.05) from 2.9 +/-
      0.2 in the DC group to 2.1 +/- 0.7 in the test group. Histological findings
      corroborate these data. The testosterone: estradiol ratio (* 10(3)) was increased
      from 4.0 +/- 0.2 in the DC group to 4.6 +/- 0.2 in the test group. The test diet
      reduced the mass and secretory activity of the enlarged prostate and may act by
      increasing the testosterone: estradiol ratio.

PMID- 22654218
TI  - Chemical and ecological evaluation of a genuine Chinese medicine: Atractylodes
      macrocephala Koidz.
AB  - The study was designated to complete a chemical and ecological evaluation of a
      genuine Chinese medicine Atractylodes macrocephala Koidz (A. macrocephala) and to
      explore the existence of correlation between chemical ingredients of different A.
      macrocephala populations and ecological factors. Different samples of A.
      macrocephala collected from six Chinese habitats were analyzed using chemical and
      ecological methods. The results showed the bioactive ingredients of A.
      macrocephala to be closely related to ecological factors. The study can serve the
      purposes of preservation and development of genuine Chinese medicines.

PMID- 22654219
TI  - Investigation of the antinociceptive and anti-inflammatory properties of
      Heteromorpha arborescens (Apiaceae).
AB  - Heteromorpha arborescens belongs to the family Apiaceae. It is commonly known as
      the parsley tree. One of its uses in the Eastern Cape Province of South Africa is
      for the treatment of abdominal pains. The therapeutic effects of the methanolic
      and aqueous root extracts of H. arborescens were investigated at two dose levels
      respectively on experimental models of pain and inflammation in rodents. The
      antinociceptive activity was evaluated using the hot-plate, abdominal
      constriction and formalin tests. The anti-inflammatory properties of these
      extracts were assessed using albumin and carrageenan as phlogistic agents. Both
      extracts produced significant (P<0.05, P<0.01) inhibition of thermal nociception
      induced by a hot plate. On chemical nociception induced by intraperitoneal acetic
      acid and subplantar formalin injection, both extracts significantly (P<0.05,
      P<0.01) decreased the number of writhing episodes and the licking time in a dose
      dependent manner. Treatment with the extracts at the same doses produced a
      significant (P<0.05, P<0.01) pain inhibition of the carrageenan induced
      inflammatory pain. Similarly, both extracts produced a significant (P<0.05,
      P<0.01) reduction of edema induced by albumin and carrageenan. These results
      suggest that both extracts of H. arborescens may act by inhibition of the
      mediators of inflammation. These findings seem to justify the use of the plant in
      traditional medicine in the management of pain and inflammation related diseases.

PMID- 22654220
TI  - Anti-inflammatory, analgesic and antipyretic effects of Lepidagathis anobrya Nees
      (Acanthaceae).
AB  - This study investigated the general acute, anti-inflammatory, analgesic and
      antipyretic effects of methanol extract of Lepidagathis anobrya Nees
      (Acanthaceae). Carrageenan-induced rat paw edema and croton oil-induced ear edema
      in rats were used for the evaluation of general acute anti-inflammatory effects.
      Acetic acid-induced writhing response and yeast-induced hyperpyrexia in mice were
      used to evaluate the analgesic and antipyretic activities respectively. The
      extract at doses of 10, 25, 50 and 100 mgkg(-1) for carrageenan test and doses of
      0.5 mg/ear for croton oil test induced a significant reduction (p < 0.001) of paw
      and ear edemas in rats. In the analgesic and antipyretic tests, the extract has
      shown a significant inhibition of writhes and hyperpyrexia with all the doses
      used when compared to the untreated control group. These results clearly show the
      anti-inflammatory, analgesic and antipyretic effects of the methanol extract of
      Lepidagathis anobrya and give the scientific basis for its traditional use.
      Further studies are needed to clarify the mechanism of action and the components
      responsible for these pharmacological effects.

PMID- 22654221
TI  - Antifertility effects of Oldenlandia affinis in male rats - a preliminary study.
AB  - Antifertility effects of an aqueous leaf extract of Oldenlandia affinis on male
      rats were investigated. The extract was administered intraperitoneally in
      sexually mature male rats at a dose of 24 mg/rat (n=8) for a total of eight
      injections over a 4 week period. There was a decrease in testis weights but all
      other accessory sex organs and vital organ weights were not affected by treatment
      with O. affinis extract. Testis histology revealed fewer spermatozoa or
      azoospermic seminiferous tubules in treated animals compared to controls with no
      change in neither tubule thickness nor Sertoli cell structure. O. affinis
      treatment caused a 17% decrease in sperm motility but there was no change in
      cauda epididymal sperm counts. However, serum testosterone levels decreased
      significantly (P<0.05) in the experimental group (602.4 +/- 57 ng/dL) compared to
      controls (808.9 +/- 55 ng/dL). These preliminary results show that the aqueous
      leaf extract of O. affinis suppresses fertility parameters in male rats.

PMID- 22654222
TI  - Comparison of the selected secondary metabolite content present in the cancer
      bush Lessertia (Sutherlandia) frutescens L. Extracts.
AB  - Extracts of in vitro leaves, field leaves and seeds of the leguminous plant
      Lessertia frutescens were analyzed using spectrophotometric and gravimetric
      methods, to the effect of quantitative comparison of their phenolic, flavonoid,
      alkaloid and saponin contents. As compared to the field leaves and seeds,
      saponins were found to be most abundantly represented in in vitro leaves,
      followed by phenolics, flavonoids and alkaloids. The extracts were also
      qualitatively analyzed so as to evaluate the presence of other phytochemicals of
      medicinal interest. This qualitative analysis indicated the presence of tannins,
      phlobatannins and cardiac glycosides. Having in mind the documented therapeutic
      use of these phytochemicals, the results of this study offer a strong rationale
      for further animal and clinical investigations of L. frutescens extracts.

PMID- 22654223
TI  - Phytochemical and biological investigations of Atriplex semibacata R .BR. growing
      in Egypt.
AB  - The lipid content of Atriplex semibacata growing in Egypt was studied. The
      unsaponifiable fraction was identified by GLC. A series of hydrocarbons ranging
      from C(14)- C(28) in addition to cholesterol, stigmasterol and the triterpenoids
      alpha and beta - amyrin were identified. GLC analysis of fatty alcohols fraction
      revealed the presence of six fatty alcohols in which dotriacontanol (C(32)H(66)O)
      was the major (14.68%). Six compounds (five coumarins and one phenolic acid) were
      isolated for the first time from A. semibacata. The coumarin constituents
      isolated from the chloroform and the ethyl acetate fractions of the aqueous
      alcoholic extract of A. semibacata were identified as scopoletin, umbelliferorne,
      coumarin, scopolin, 7-methoxy coumarin in addition to a phenolic acid P-coumaric
      acid. Also, the flavonoidal compounds isolated from the n-butanol fraction of the
      plant revealed the presence of kaempferol 3-O glucoside and acacetin. Their
      identity was proved by m.p., TLC, PC, UV and MS analysis. The alcohol extract
      showed significant antimicrobial activity against G-ve bacteria, moderate
      activity against G+ve bacteria. On the other hand, the pet. Ether extract showed
      marked activity against G+ve bacteria and fungi, also the G-ve bacteria was
      greatly inhibited by the chloroform extract. The different extracts of the plant
      exhibited no cytotoxic activity against Erlich-ascites carcinoma cells line at
      the tested concentrations, also showed a strong antioxidant activity using DPPH.

PMID- 22654224
TI  - Haemostatic effect of Ankaferd Blood Stopper((r)) seen during adenoidectomy.
AB  - In Turkey, Ankaferd Blood Stopper((r)) (ABS) has been approved for the management
      of external haemorrhages and bleedings occurring during dental surgeries (Goker
      et al., 2008). Ankaferd comprises a standardized mixture of plants, including
      Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and
      Urtica diodica. This study aimed to evaluate the efficacy of AB S tam ponade in
      the control of intra-operative bleeding occurring during ad enoidectomy performed
      in children under the age of 12. Sixty children were randomized to receive 1 to 5
      minute-tamponade with either ABS or topical gauze sponges soaked in saline
      solution (SS) during their ad enoidectomy.. Time-to-haemostasis and the number of
      packs required were recorded. A visual analog scale was used by the operating
      surgeon to record subjective data, including the rate of bleeding following the
      first adenoid pack removal (0= none, 3=brisk). Compared to the children in the SS
      group (n=30), time-to-haemostasis seen in ABS patients (n=30) was significantly
      shorter (mean +/- standard deviation, 1.93 +/- 1.39 min vs 3.20 +/- 1.50 min;
      p<0.0001); they required a lower number of packs (mean, 1.93 vs. 3.20), and
      appeared to bleed less (53.3% vs 6.7%; p=0.0001). ABS aids in the control of
      intra-operative bleeding and reduces the number of packs required to achieve
      haemostasis, so that it can be recommended for tamponades per formed during
      paediatric adenoidectomies.

PMID- 22654225
TI  - Molluscicidal effect of Piper guineense.
AB  - The study was undertaken to assess the dosage-mortality ratio and toxic effects
      of Piper guineense fruit extracts on the adults of Biomphalaria pfeifferi, the
      snail intermediate host of Schistosoma mansoni, which causes intestinal
      schistosomiasis. The result showed significant toxic effects with crude ethanol
      and hot water fruits extracts. The estimated lethal dose concentration by
      arithmetic method (LC(50) and LC(90)) using both crude ethanol and hot water
      fruit media extracts were found to be (0.10 +/- 0.04, 0.9 +/- 0.2) mgl(-1)
      respectively for ethanolic extract and (5.0 +/- 1.4, 8.5 +/- 0.7) mgl(-1)
      respectively for hot water extract. Ethanolic extract was more potent than hot
      water extract. An all or none phenomenon appeared characteristic of the
      biological activity of these extracts. There was significant decrease in
      oviposition rate (p < 0.02). The extract from the fruits of this tropical plant
      holds promise in the control of Biomphalaria pfeifferi.

PMID- 22654227
TI  - Evaluation of analgesic and anti-inflammatory effects of ethanol extract of Ficus
      iteophylla leaves in rodents.
AB  - This study was undertaken to investigate the leaf part of the plant for analgesic
      and anti-inflammatory. The ethanol extract of Ficus iteophylla leaves (100, 200,
      and 400 mg kg(-1), i.p) was evaluated for analgesic and anti-inflammatory
      activities. The analgesic effect was studied using acetic acid-induced abdominal
      constriction and hot plate test in mice, while the anti-inflammatory effect was
      investigated using carrageenan induced paw oedema in rats. The ethanol extract at
      100 mg kg(-1), 200 mg kg(-1), and 400 mg kg(-1) significantly (P< 0.05) inhibited
      acetic acid induced writhes by 1.50 +/- 0.43, 3.0 +/- 0.82 and 1.0 +/- 0.82
      respectively. It also exhibited significantly (P< 0.05) anti-inflammatory by 0.11
      +/- 0.02, 0.11 +/- 0.03, 0.08 +/- 0.01 respectively. The preliminary
      phytochemical screening of the plant extract revealed the presence of flavonoids,
      steroids, tannins and saponins while the effect of flavonoids, steroids and
      tannins on analgesic and inflammatory has been reported. The intraperitoneal
      median lethal dose (LD(50)) value of the extract was found to be 3807.8 mgkg(-1)
      body weights. The result obtained from this study shows that the extract of Ficus
      iteophylla contained phytochemical constituents with analgesic and anti
      inflammatory activities, therefore the leaf part of the plant could be used in
      the management of pain and inflammatory conditions.

PMID- 22654226
TI  - Anacardium occidentale Linn. (Anacardiaceae) stem bark extract induces
      hypotensive and cardio-inhibitory effects in experimental animal models.
AB  - Anacardium occidentale Linn. (Anacardiaceae) is a plant largely used in Africa
      for the treatment of different diseases. In Cote d'Ivoire it's commonly used for
      the treatment of hypertension. The present study was carried out in order to
      assess the effects of Anacardium occidentale extract (ANOE) on cardiovascular
      parameters in animal models. A mercury manometer kymograph of Ludwig was used to
      measure the blood pressure of normotensive rabbits in control conditions (normal
      physiological solution) and under the influence of ANOE. The contractile activity
      of an isolated rat heart was also measured in control conditions and under the
      influence of ANOE in different physiological media using a modified Langendhorff
      (1895) apparatus. The aqueous Anacardium occidentale (ANOE) bark extract applied
      intravenously in different doses (12, 40, 90, and 167 mg/kg b.w.), produced a
      significant dose-dependent decrease in blood pressure of previously normotensive
      rabbits (up to 89% vs control). Atropine (1 mg/ml) pre-treatment failed to
      reverse the hypotensive effects elicited by the extract. ANOE applied to isolated
      rat heart preparations in different concentrations (0.01, 0.1, 1.0, and 10 ug/ml)
      induced negative inotropic and chronotropic effects. Atropine pre-treatment of
      heart preparations (0.1 ug/ml) failed to reverse the negative effects induced by
      ANOE. The extract's action on heart contractile activity studied in modified
      culture media further confirmed its cardio-inhibitory effects. ANOE induced
      strong hypotensive and cardio-inhibitory effects in animal models.

PMID- 22654228
TI  - Effect of Shen-qi-di-huang decoction on reducing proteinuria by preserving
      nephrin in adriamycin-induced nephropathy rats.
AB  - The aim of this study is to investigate the effect of Shen-qi-di-huang decoction
      on reducing proteinuria and to discuss the mechanism of its action in Adriamycin
      (ADR)-induced nephropathy rats. The rats were randomly divided into three groups
      (n=12 each group): normal control (group A); ADR model control (group B); ADR +
      Shen-qi-di-huang decoction (group C). In group B and C, the rats were
      intravenously injected with ADR (6.5mg/kg). The rats in group C were orally
      administrated with Shen-qi-di-huang decoction after the injection of ADR. On day
      7, 14, 28, 56 after ADR injection, 24h urine protein was detected. On day 28, 56
      after ADR injection, ALB, ALT, serum creatinine (Scr) and BUN were examined. The
      morphological changes of the kidneys were observed by light microscope and
      electron microscope on day 28, 56 after ADR injection. The expression of nephrin
      was determined by immunohistochemistry and RT-PCR on day 28, 56 after ADR
      injection. Compared with group B, 24h urine protein and Scr decreased in group C
      on day 56 (P<0.05). The expression of nephrin determined by immunohistochemistry
      and RT-PCR increased in group C on day 28, 56 (P<0.05). The morphology observed
      by light microscope and electron microscope improved in group C on day 28, 56.
      Shen-qi-di-huang decoction decreases proteinuria, protects kidney function, and
      ameliorates histopathology in ADR-induced rats by preserving nephrin expression.

PMID- 22654230
TI  - Filling in the gaps before clients fall through the cracks: physiotherapists have
      the skills to help clients preserve bone and prevent falls.

PMID- 22654229
TI  - Determination of parameters affecting the use of complementary and alternative
      medicine in cancer patients and detection of prevalence of use.
AB  - This study was conducted to find out the frequency of complementary and
      alternative medicine (CAM) use that could lead to troubles in patient health and
      in applied standard therapy protocols when used improperly, which method is used,
      the reasons for use and from which resources the information about this topic
      were obtained. A questionnaire consisting of 28 questions was applied to 195
      patients with cancer diagnosis by a face-to-face interview. The obtained data
      were assessed with SPSS 11.5 program. Out of 195 cancer patients, 100 (51.3%)
      were using CAM and 48.7% (n=95) were not. The most commonly used agent was nettle
      (72%). This was followed by herbal teas (21%), grape molasses (20%) and black
      seed (20%). The frequency of CAM use was found higher in those under age 50, in
      literate people, in those working during the diagnosis stage and having disease
      at the later stage. While CAM was commonly recommended by friends and relatives
      of the patients (73%), this ratio was only 5% for health professionals. While
      51.3% of all patients were gathering information about CAM, 75% of those actually
      using CAM gathered information about it. Whilst information was gathered mostly
      from the relatives of patients and tamperers (47%), it can be gathered from
      physicians only with a ratio of 10%. Cancer patients use CAM and they gather
      information mainly from unreliable sources rather than physicians. Although the
      primary information source should be physicians, the ratio for this was very low
      (10%). We suggest that physicians should spend more time in gathering correct
      information and sharing them with their patients for a better guidance.

PMID- 22654232
TI  - Clinician's Commentary on Cott et al.(1).

PMID- 22654231
TI  - Models of integrating physical therapists into family health teams in ontario,
      Canada: challenges and opportunities.
AB  - PURPOSE: To explore the potential for different models of incorporating physical
      therapy (PT) services within the emerging network of family health teams (FHTs)
      in Ontario and to identify challenges and opportunities of each model. METHODS: A
      two-phase mixed-methods qualitative descriptive approach was used. First, FHTs
      were mapped in relation to existing community-based PT practices. Second, semi
      structured key-informant interviews were conducted with representatives from
      urban and rural FHTs and from a variety of community-based PT practices.
      Interviews were digitally recorded, transcribed verbatim, and analyzed using a
      categorizing/editing approach. RESULTS: Most participants agreed that the ideal
      model involves embedding physical therapists directly into FHTs; in some
      situations, however, partnering with an existing external PT provider may be more
      feasible and sustainable. Access and funding remain the key issues, regardless of
      the model adopted. CONCLUSION: Although there are differences across the
      urban/rural divide, there exist opportunities to enhance and optimize existing
      delivery models so as to improve client access and address emerging demand for
      community-based PT services.

PMID- 22654233
TI  - The Alberta Health Technology Assessment (HTA) Ambassador Program: The
      Development of a Contextually Relevant, Multidisciplinary Clinical Practice
      Guideline for Non-specific Low Back Pain: A Review.
AB  - PURPOSE: To describe the development of a contextually relevant multidisciplinary
      clinical practice guideline (CPG) for non-specific low back pain (LBP) and to
      discuss its value to the management of LBP and the practice of physiotherapy.
      METHOD: To mitigate an identified knowledge gap for Alberta primary-care
      practitioners in the management of non-specific LBP, a collaborative process was
      developed to engage multidisciplinary health care providers in designing a
      primary-care CPG for non-specific LBP. A comprehensive review of published LBP
      guidelines identified the seven highest-quality CPGs; these were used to inform a
      multidisciplinary guideline development group (GDG) as they developed the CPG.
      RESULTS: The GDG constructed a CPG for non-specific LBP along with point-of-care
      decision-support and patient-education tools. CONCLUSIONS: The Ambassador Program
      on Low Back Pain worked with front-line clinicians from across Alberta to review
      the best available evidence in developing a CPG responsive to the Alberta
      context. This CPG is intervention specific and provides a wide range of primary
      care practitioners with the best available evidence to inform their clinical
      decisions in managing non-specific LBP.

PMID- 22654234
TI  - Clinician's Commentary on Cutforth et al.(1).

PMID- 22654236
TI  - Interactions between Pain and the Motor Cortex: Insights from Research on Phantom
      Limb Pain and Complex Regional Pain Syndrome.
AB  - PURPOSE: Pain is a significantly disabling problem that often interacts with
      other deficits during the rehabilitation process. The aim of this paper is to
      review evidence of interactions between pain and the motor cortex in order to
      attempt to answer the following questions: (1) Does acute pain interfere with
      motor-cortex activity? (2) Does chronic pain interfere with motor-cortex
      activity, and, conversely, does motor-cortex plasticity contribute to chronic
      pain? (3) Can the induction of motor plasticity by means of motor-cortex
      stimulation decrease pain? (4) Can motor training result in both motor-cortex
      reorganization and pain relief? SUMMARY OF KEY POINTS: Acute experimental pain
      has been clearly shown to exert an inhibitory influence over the motor cortex,
      which can interfere with motor learning capacities. Current evidence also
      suggests a relationship between chronic pain and motor-cortex reorganization, but
      it is still unclear whether one causes the other. However, there is growing
      evidence that interventions aimed at normalizing motor-cortex organization can
      lead to pain relief. CONCLUSIONS: Interactions between pain and the motor cortex
      are complex, and more studies are needed to understand these interactions in our
      patients, as well as to develop optimal rehabilitative strategies.

PMID- 22654237
TI  - Development of a theory-based intervention to increase prescription of
      inspiratory muscle training by health professionals in the management of people
      with chronic obstructive pulmonary disease.
AB  - PURPOSE: The purpose of this paper is twofold: (1) to provide an overview of the
      literature on barriers to evidence-based practice (EBP) and the effectiveness of
      implementation interventions in health care; and (2) to outline the development
      of an implementation intervention for improving the prescription of inspiratory
      muscle training (IMT) by physical therapists and other health professionals for
      people with chronic obstructive pulmonary disease (COPD). SUMMARY OF KEY POINTS:
      Individuals, organizations, and the research itself present barriers to EBP in
      physical therapy. Despite the evidence supporting the use of IMT, this treatment
      continues to be under-used in managing COPD. Current health services research
      shows that traditional information-based approaches to implementation, such as
      didactic lectures, do not adequately address the challenges health professionals
      face when trying to make changes in practice. We propose the development of a
      theory-based intervention to improve health professionals' use of IMT in the
      management of COPD. It is postulated that a behavioural intervention, based on
      the theory of planned behaviour (TPB), may be more effective than an information
      based strategy in increasing the prescription of IMT by health professionals.
      CONCLUSION: TPB may be used to understand the antecedents of health
      professionals' behaviour and to guide the development of implementation
      interventions. Further research is needed to evaluate the effectiveness of this
      proposed intervention in the management of people with COPD.

PMID- 22654235
TI  - Strategies Aimed at Preventing Chronic Post-surgical Pain: Comprehensive
      Perioperative Pain Management after Total Joint Replacement Surgery.
AB  - PURPOSE: Chronic post-surgical pain (CPSP) is a frequent outcome of
      musculoskeletal surgery. Physiotherapists often treat patients with pain before
      and after musculoskeletal surgery. The purposes of this paper are (1) to raise
      awareness of the nature, mechanisms, and significance of CPSP; and (2) to
      highlight the necessity for an inter-professional team to understand and address
      its complexity. Using total joint replacement surgeries as a model, we provide a
      review of pain mechanisms and pain management strategies. SUMMARY OF KEY POINTS:
      By understanding the mechanisms by which pain alters the body's normal
      physiological responses to surgery, clinicians selectively target pain in post
      surgical patients through the use of multi-modal management strategies.
      Clinicians should not assume that patients receiving multiple medications have a
      problem with pain. Rather, the modern-day approach is to manage pain using
      preventive strategies, with the aims of reducing the intensity of acute
      postoperative pain and minimizing the development of CPSP. CONCLUSIONS: The roles
      of biological, surgical, psychosocial, and patient-related risk factors in the
      transition to pain chronicity require further investigation if we are to better
      understand their relationships with pain. Measuring pain intensity and analgesic
      use is not sufficient. Proper evaluation and management of risk factors for CPSP
      require inter-professional teams to characterize a patient's experience of
      postoperative pain and to examine pain arising during functional activities.

PMID- 22654239
TI  - Estimating the Accuracy of the Chedoke-McMaster Stroke Assessment Predictive
      Equations for Stroke Rehabilitation.
AB  - PURPOSE: To estimate the predictive accuracy and clinical usefulness of the
      Chedoke-McMaster Stroke Assessment (CMSA) predictive equations. METHOD: A
      longitudinal prognostic study using historical data obtained from 104 patients
      admitted post cerebrovascular accident was undertaken. Data were abstracted for
      all patients undergoing rehabilitation post stroke who also had documented
      admission and discharge CMSA scores. Published predictive equations were used to
      determine predicted outcomes. To determine the accuracy and clinical usefulness
      of the predictive model, shrinkage coefficients and predictions with 95%
      confidence bands were calculated. RESULTS: Complete data were available for 74
      patients with a mean age of 65.3+/-12.4 years. The shrinkage values for the six
      Impairment Inventory (II) dimensions varied from -0.05 to 0.09; the shrinkage
      value for the Activity Inventory (AI) was 0.21. The error associated with
      predictive values was greater than +/-1.5 stages for the II dimensions and
      greater than +/-24 points for the AI. CONCLUSIONS: This study shows that the
      large error associated with the predictions (as defined by the confidence band)
      for the CMSA II and AI limits their clinical usefulness as a predictive measure.
      Further research to establish predictive models using alternative statistical
      procedures is warranted.

PMID- 22654238
TI  - Can administrative claim file review be used to gather physical therapy,
      occupational therapy, and psychology payment data and functional independence
      measure scores? Implications for rehabilitation providers in the private health
      sector.
AB  - PURPOSE: Rehabilitation costs for spinal-cord injury (SCI) are increasingly borne
      by Canada's private health system. Because of poor outcomes, payers are
      questioning the value of their expenditures, but there is a paucity of data
      informing analysis of rehabilitation costs and outcomes. This study evaluated the
      feasibility of using administrative claim file review to extract rehabilitation
      payment data and functional status for a sample of persons with work-related SCI.
      METHODS: Researchers reviewed 28 administrative e-claim files for persons who
      sustained a work-related SCI between 1996 and 2000. Payment data were extracted
      for physical therapy (PT), occupational therapy (OT), and psychology services.
      Functional Independence Measure (FIM) scores were targeted as a surrogate measure
      for functional outcome. Feasibility was tested using an existing approach for
      evaluating health services data. RESULTS: The process of administrative e-claim
      file review was not practical for extraction of the targeted data. CONCLUSIONS:
      While administrative claim files contain some rehabilitation payment and outcome
      data, in their present form the data are not suitable to inform rehabilitation
      services research. A new strategy to standardize collection, recording, and
      sharing of data in the rehabilitation industry should be explored as a means of
      promoting best practices.

PMID- 22654240
TI  - Clinician's Commentary on Dang et al.(1).

PMID- 22654241
TI  - Applying motor-control theory to physical therapy practice: a case report.
AB  - PURPOSE: This case report describes the application of an integrated, systems
      based theory of motor control to physical therapy practice.Client Description:
      The patient was a 5-year-old boy with spastic hemiplegic cerebral palsy who was
      entering kindergarten. Parent concerns related to the child's safety in
      playground activities such as playing on the slide. INTERVENTIONS: Motor-control
      theory, including factors related to the task, the environment, and the
      individual, was used to guide and direct physical therapy management related to
      the patient goal of safely and effectively climbing the ladder to the playground
      slide.Patient Outcomes: When the child entered kindergarten, he was able to
      safely ascend the ladder to the playground slide, using a modified movement
      pattern, when distractions were minimized. However, attentional issues continued
      to affect task execution when other children were present. IMPLICATIONS: This
      case report demonstrates a means by which current knowledge and theory can be
      integrated into clinical practice. FUTURE DIRECTIONS: Applying motor-control
      theory to this case led to the development of clinical questions for future
      research.

PMID- 22654243
TI  - Cardiovascular fitness training for a patient in the early stages of recovery
      post stroke.

PMID- 22654242
TI  - Morphological, electrophysiological, and metabolic characteristics of skeletal
      muscle in people with end-stage renal disease: a critical review.
AB  - PURPOSE: Fatigue is one of the most frequent debilitating symptoms reported by
      people with end-stage renal disease (ESRD) on haemodialysis (HD) therapy. A wide
      range of underlying abnormalities, including skeletal muscle weakness, have been
      implicated as causes of this fatigue. Skeletal muscle weakness is well
      established in this population, and such muscle weakness is amenable to physical
      therapy treatment. The purpose of this review was to identify morphological,
      electrophysiological, and metabolic characteristics of skeletal muscles in people
      with ESRD/HD that may cause skeletal muscle weakness. METHOD: Electronic
      databases were searched for relevant literature from inception to March 2010.
      Inclusion criteria were English language; adult subjects with ESRD/HD; and the
      use of muscle biopsy, electromyography, and nuclear magnetic spectroscopy ((31)P
      NMRS) techniques to evaluate muscle characteristics. RESULTS: In total, 38
      studies were included. All studies of morphological characteristics reported type
      II fibre atrophy. Electrophysiological characteristics included both neuropathic
      and myopathic skeletal muscle changes. Studies of metabolic characteristics
      revealed higher cytosolic inorganic phosphate levels and reduced effective muscle
      mass. CONCLUSION: The results indicate an array of changes in the morphological,
      electrophysiological, and metabolic characteristics of skeletal muscle structure
      in people with ESRD/HD that may lead to muscle weakness.

PMID- 22654244
TI  - What Does the Cochrane Collaboration Say about the Treatment of Pain?

PMID- 22654245
TI  - When will the evidence catch up with clinical practice?

PMID- 22654247
TI  - Life, liberty, and the pursuit of quality?

PMID- 22654246
TI  - A Qualitative Investigation of Practicing Psychologists' Attitudes Toward
      Research-Informed Practice: Implications for Dissemination Strategies.
AB  - This article presents the results of a qualitative analysis of interviews with 25
      psychologists in independent practice, investigating everyday treatment decisions
      and attitudes about treatment outcome research and empirically supported
      treatments (ESTs). Clinicians noted positive aspects about treatment outcome
      research, such as being interested in what works. However, they had misgivings
      about the application of controlled research findings to their practices, were
      skeptical about using manualized protocols, and expressed concern that
      nonpsychologists would use EST lists to dictate practice. Clinicians reported
      practicing in an eclectic framework, and many reported including cognitive
      behavioral elements in their practice. To improve their practice, they reported
      valuing clinical experience, peer networks, practitioner-oriented books, and
      continuing education when it was not too basic. Time and financial barriers
      concerned nearly all participants. Clinicians suggested they might be interested
      in ESTs if they could integrate them into their current frameworks, and if
      resources for learning ESTs were improved.

PMID- 22654248
TI  - Radioembolization complicated by dissection of the common femoral artery.
AB  - The common femoral artery is the most frequently used access site for
      angiographic procedures in interventional radiology. Potential complications of
      common femoral arteriotomy include hematoma formation, pseudoaneurysm,
      uncontrolled groin or retroperitoneal bleeding, acute arterial occlusion,
      dissection, and arteriovenous fistula formation. In a case such as the one
      described here, with a common femoral artery dissection with intraluminal
      thrombus and vessel occlusion, the complication may have occurred at the time of
      access or at the time of closure, with both procedure-associated and patient
      specific risk factors affecting the overall risk of complications. Though some
      studies have shown an increased risk of complications with the use of arterial
      closure devices, others have found no increase. In any patient with symptoms
      following a femoral arteriotomy, rapid diagnosis and treatment is necessary to
      avoid further complications. Both patient-specific and procedure-associated risk
      factors should be considered prior to arteriotomy and usage of an arterial
      closure device.

PMID- 22654249
TI  - Percutaneous renal cryoablation complicated by hemorrhage.
AB  - The authors describe a case in which a patient underwent percutaneous
      cryoablation of a suspected right renal cell carcinoma complicated by bleeding.
      Urgent angiography revealed a lower renal pole arteriovenous (AV) fistula,
      correlating with the recent treatment site. This AV fistula was successfully
      treated with coil and Gelfoam embolization. Three days later, the patient's
      hemoglobin dropped following dialysis. Computed tomography (CT) imaging revealed
      an increase in the size of the pararenal hematoma. There were multiple
      pseudoaneurysms as well as a small AV fistula on repeat angiography. The right
      main renal artery was coil embolized.

PMID- 22654250
TI  - Hepatic artery dissection in a patient on bevacizumab resulting in pseudoaneurysm
      formation.
AB  - Interventional radiologists are frequently encountering patients with colorectal
      cancer that are being treated with bevacizumab. This therapeutic agent is
      associated with a potentially increased risk of adverse events when invasive
      procedures are performed while patients are on therapy. The current case report
      reviews a complication related to planning angiography for radioembolization with
      Yttrium-90 microspheres in an individual on bevacizumab and subsequent management
      of the patient.

PMID- 22654251
TI  - Endovascular stent reconstruction of the inferior vena cava complicated by
      duodenocaval fistula.
AB  - A patient with retroperitoneal metastatic uterine adenocarcinoma resulting in
      symptomatic occlusion of the inferior vena cava underwent palliative endovascular
      stent reconstruction and subsequent radiation therapy. She then developed sepsis
      and massive lower gastrointestinal bleeding. Computed tomography (CT) and
      cavography demonstrated a fistulous communication between the duodenum and the
      stented segment of inferior vena cava. Deployment of endovascular stent graft
      devices successfully occluded the fistulous communication and resulted in
      clinical improvement.

PMID- 22654253
TI  - Acute Thrombosis of Left Portal Vein during Right Portal Vein Embolization
      Extended to Segment 4.
AB  - Portal vein thrombosis (PVT) is an uncommon, but potentially devastating
      complication of portal vein embolization (PVE). Its occurrence relates to both
      local and systemic risk factors. In the setting of PVE, precipitating factors
      include injury to the vessel wall and reduced portal flow. Contributory factors
      include portal hypertension, hypercoagulopathy, inflammatory processes,
      malignancy, pregnancy, oral contraceptive use, and asplenia. The goal of therapy
      is to prevent thrombus progression and lyse existing clot. Hepatectomy is
      impossible if adequate recanalization has not occurred and/or overt portal
      hypertension develops. The mechanisms for thrombus development, its diagnosis,
      management, and prognosis are discussed.

PMID- 22654252
TI  - Microwave lung ablation complicated by bronchocutaneous fistula: case report and
      literature review.
AB  - Microwave ablation is a developing treatment option for unresectable lung cancer.
      Early experience suggests that it may have advantages over radiofrequency (RF)
      ablation with larger ablation zones, shorter heating times, less susceptibility
      to heat sink, effectiveness in charred lung, synergism with multiple applicators,
      no need for grounding pads, and similar survival benefit. Newer microwave
      ablation devices are being developed and as their use becomes more prevalent, a
      greater understanding of device limitations and complications are important.
      Herein we describe a microwave lung ablation complicated by bronchocutaneous
      fistula (BCF) and its treatment. BCF treatment options include close monitoring,
      surgical closure, percutaneous sealant injection, and endoscopic plug or sealant
      in those who are not surgical candidates.

PMID- 22654254
TI  - Pulmonary radiofrequency ablation complicated by acute respiratory distress
      syndrome.
AB  - The authors present a case of a patient with rectal adenocarcinoma and lung
      metastasis undergoing elective radiofrequency (RF) ablation of a large,
      refractory pulmonary metastasis. The mass was located in the left upper lobe,
      invading the left hilum. The patient experienced shortness of breath following
      the procedure and shortly after extubation. This shortness of breath progressed
      over 4 days, when the patient developed acute respiratory distress syndrome
      (ARDS). The patient suffered from complications related to respiratory support
      and expired 9 days after RF ablation. Possible mechanisms of ARDS development
      following pulmonary ablation are discussed.

PMID- 22654255
TI  - Iatrogenic Brachial Plexopathy due to Improper Positioning during Radiofrequency
      Ablation.
AB  - Iatrogenic peripheral nerve injuries are a common source of postprocedural
      morbidity. The authors present a case report of a patient who developed brachial
      plexopathy from positioning during radiofrequency ablation of a renal mass.
      Though incidence data on the majority of iatrogenic peripheral nerve injury is
      scarce, there is more concrete data on iatrogenic brachial plexopathy. The
      incidence of brachial plexopathies is ~0.2% of all patients who receive general
      anesthesia, with between 7 and 10% of brachial plexopathies being iatrogenic in
      nature. The mechanism of injury in the majority of cases is due to stretching or
      compression of the nerve tissue. Treatment is largely supportive. Prevention is
      key in minimizing this form of patient morbidity. It is the operator's
      responsibility to mitigate this risk by employing proper positioning techniques
      and communicating closely with the anesthesia staff when applicable.

PMID- 22654256
TI  - Radiofrequency ablation of a solitary liver metastasis complicated by colonic
      perforation.
AB  - Radiofrequency ablation is used for the treatment of primary liver malignancies
      and liver metastases. In this case, the authors performed percutaneous
      radiofrequency ablation of a solitary esophageal carcinoma metastasis within the
      left hepatic lobe. Following the procedure, the patient developed a colonic
      perforation with a large right upper quadrant abscess. Although the abscess
      nearly resolved after intravenous antibiotics and percutaneous drainage, the
      patient ultimately developed a colocutaneous fistula that required surgical
      excision and right hemicolectomy. The risks for developing this complication as
      well as measures to minimize this risk are discussed.

PMID- 22654257
TI  - Radiofrequency ablation of pulmonary neoplasm complicated by pulmonary
      hemorrhage.
AB  - Pulmonary hemorrhage is a potentially serious complication of radiofrequency
      ablation of pulmonary neoplasms that may occur with or without hemoptysis.
      Several factors influence the development of parenchymal hemorrhage, including
      tumor size, tumor location, and procedural technique. As radiofrequency ablation
      has become more common, the prompt diagnosis and appropriate treatment of
      hemorrhage is vital. The authors report a case of radiofrequency ablation of a
      solitary pulmonary metastasis complicated by pulmonary hemorrhage and hemoptysis.

PMID- 22654258
TI  - Radiofrequency ablation complicated by skin burn.
AB  - Radiofrequency (RF) ablation has been increasingly utilized as a minimally
      invasive treatment for primary and metastatic liver tumors, as well as tumors in
      the kidneys, bones, and adrenal glands. The development of high-current RF
      ablation has subsequently led to an increased risk of thermal skin injuries at
      the grounding pad site. The incidence of skin burns in recent studies ranges from
      0.1-3.2% for severe skin burns (second-/third-degree), and from 5-33% for first
      degree burns.(1-3).

PMID- 22654259
TI  - Pulmonary radiofrequency ablation complicated by tension pneumothorax.
AB  - Pneumothorax is a common complication of radiofrequency ablation of pulmonary
      lesions. During a treatment session, a moderate pneumothorax was initially
      managed by placement of a pigtail catheter. Due to technical considerations,
      ablation of the lesion was not performed; given resolution of the pneumothorax,
      the pigtail catheter was removed. However, after a short time, the patient's
      vital signs abruptly deteriorated and the diagnosis of tension pneumothorax was
      made clinically. A small-gauge catheter was emergently inserted with prompt
      improvement in the patient's condition, and a chest tube was subsequently placed
      via this access in the interventional department for definitive treatment.

PMID- 22654260
TI  - Tract seeding following radiofrequency ablation for hepatocellular carcinoma:
      prevention, detection, and management.
AB  - Radiofrequency ablation (RFA) has become an important tool in the armamentarium
      of interventional oncology, particularly in the treatment of primary
      hepatocellular carcinoma and metastatic tumors. This procedure has proven to be
      an effective adjunct in treating hepatic tumors as a bridge to liver
      transplantation, and has a low complication profile. Although adverse events are
      rare and usually minor, a notable negative outcome is dissemination and
      implantation of viable tumor cells into the route of applicator entry, or tract
      seeding. Counter to the goal of treating a patient's cancer, this results in
      metastatic disease. In this report, the authors present 2 cases of tract seeding
      after RFA, methods of detection, and means of reducing the incidence of this
      relatively rare, but significant, complication.

PMID- 22654261
TI  - Hepatic abscess complicating transarterial chemoembolization in a patient with
      liver metastases.
AB  - Hepatic abscess following transarterial chemoembolization is an uncommon
      complication. The authors describe a case of liver abscess after transarterial
      chemoembolization for neuroendocrine liver metastases, including risk factors,
      prophylaxis, treatment, and outcomes.

PMID- 22654262
TI  - Transarterial chemoembolization complicated by deteriorating hepatic function.
AB  - Worsening hepatic function is a well-known potential complication of
      chemoembolization and occurs in up to 58% of patients undergoing
      chemoembolization. Although liver function returns to baseline levels within 3-4
      weeks in the majority of patients, fulminant liver failure and death occur with a
      reported frequency of ~2-10%. Poor performance status, portal vein obstruction,
      biliary obstruction, extensive tumor burden, and Child-Pugh status B or C are
      among factors predisposing to an increased risk of transient or fulminant hepatic
      failure, with Child-Pugh status being the most accurate. Unless the patient is a
      candidate for liver transplantation, treatment for hepatic failure is limited to
      supportive measures.

PMID- 22654263
TI  - Nontarget embolization complicating transarterial chemoembolization in a patient
      with hepatocellular carcinoma.
AB  - Nontarget embolization during transarterial chemoembolization, although
      infrequent, can be a serious complication. The authors describe a case of
      nontarget gastric embolization to the stomach after transarterial
      chemoembolization and describe the published incidence of nontarget embolization
      to various organs, its diagnosis, treatment, and possible outcomes.

PMID- 22654264
TI  - Hepatic transcatheter arterial chemoembolization complicated by postembolization
      syndrome.
AB  - Postembolization syndrome (PES) is a common complication after embolic
      procedures, and it is a frequent cause of extended inpatient hospital admissions.
      PES is a self-limited constellation of symptoms consisting of fevers, unremitting
      nausea, general malaise, loss of appetite, and variable abdominal pain following
      the procedure. Although a definite cause is unknown, this syndrome is thought to
      be a result of therapeutic cytotoxicity, tumor ischemia, and resulting
      intrahepatic and extrahepatic inflammation. The authors report a case of PES
      precipitated by transcatheter intrarterial chemoembolization of hepatic
      metastases.

PMID- 22654265
TI  - Chemoembolization with drug-eluting beads complicated by intrahepatic biloma.
AB  - Chemoembolization with drug-eluting beads is a type of locoregional therapy
      currently being used for the treatment of hepatocellular carcinoma and metastatic
      disease to the liver. This treatment has proven effectiveness in controlling
      tumor growth, extending survival time, and improving quality of life.
      Chemoembolization with drug-eluting beads have been shown to be safe, but like
      any other invasive procedure, can have associated complications. The authors
      present a case of intrahepatic biloma formation occurring as a result of
      treatment with drug-eluting beads.

PMID- 22654266
TI  - Chemoembolization of hepatocellular carcinoma with drug-eluting beads complicated
      by interstitial pneumonitis.
AB  - Transarterial chemoembolization has proven benefit in the treatment of
      unresectable hepatocellular carcinoma (HCC). Commonly reported symptoms following
      chemoembolization with or without drug-eluting beads include abdominal pain,
      nausea, and low-grade fever, which typically limited resolve within a few days. A
      recent study comparing traditional chemoembolization versus chemoembolization
      with drug-eluting beads demonstrated similar survival between the two techniques,
      but improved tolerability when the drug-eluting beads were used. This case report
      describes a patient with unresectable HCC undergoing chemoembolization with drug
      eluting beads. The postprocedure course was complicated by interstitial
      pneumonitis secondary to shunting of the drug-eluting beads containing
      doxorubicin to both lungs via tumor vasculature. This case highlights the
      relationship between the number and size of the tumors to be treated,
      arteriovenous shunting within the liver/tumors, and the size of the embolization
      particles.

PMID- 22654267
TI  - Hepatic radioembolization complicated by abscess.
AB  - Hepatic abscess is a rare complication of yttrium-90 radioembolization of hepatic
      tumors that most commonly occurs in patients with a history of biliary
      intervention. Patients usually present several weeks after therapy with pain,
      nausea, vomiting, and fever. Cross-sectional imaging is necessary in cases of
      suspected abscess to ensure prompt diagnosis and to help plan treatment, which
      involves antibiotics and percutaneous drainage.

PMID- 22654268
TI  - Radioembolization for hepatocellular carcinoma complicated by biliary stricture.
AB  - The authors present a case of radiation-induced biliary stricture following
      yttrium-90 ((90)Y) radioembolization for hepatocellular carcinoma. Biliary
      complications (e.g., biliary stricture, biliary necrosis, biloma) following
      radioembolization and other locoregional therapies are uncommon and usually
      managed conservatively. In instances when biliary injury is refractory to medical
      management, as in the case presented herein, endoscopic, percutaneous, or
      surgical intervention may be required. Timely diagnosis of biliary complications
      with correlation to liver function permits optimal clinical management of
      patients undergoing (90)Y radioembolization.

PMID- 22654269
TI  - Hepatic radioembolization complicated by radiation cholecystitis.
AB  - Biliary complications following yttrium-90 ((90)Y) radioembolization are rare,
      and radiation-induced cholecystitis requiring intervention represents an even
      smaller proportion of these complications, reportedly occurring in fewer than 1%
      of patients treated with (90)Y [1]. However, its implications are serious, as the
      treatment of radiation cholecystitis may require cholecystectomy in patients
      otherwise considered poor surgical candidates. While biliary complications such
      as intrahepatic biliary strictures or bilomas may be unavoidable in the course of
      treating hepatic malignancies due to local field effects of radiation, radiation
      cholecystitis results from non-target embolization of radioactive microspheres.
      Meticulous attention to anatomic detail and catheter position may be adequate in
      preventing this avoidable complication. Herein we discuss the clinical,
      radiographic, and pathologic findings, as well as the outcome, of a patient who
      experienced radiation cholecystitis following (90)Y radioembolization.

PMID- 22654270
TI  - Radioembolization complicated by nontarget embolization to the falciform artery.
AB  - The most common application of radioembolization is in the treatment of primary
      and secondary liver tumors, and the most common radioisotope is Yttrium-90. This
      form of treatment has proven to be successful in achieving reduction of tumor
      size and ultimately improving survival. Fatigue and nausea/vomiting are the most
      common side effects related to radioembolization and are usually self-limiting.
      This report describes a case of abdominal pain caused by shunting of yttrium-90
      microspheres to the anterior abdominal wall via a patent hepatic falciform
      artery. This case highlights the need for vigilant angiography and awareness of
      the falciform artery with prophylactic embolization when necessary/warranted.

PMID- 22654271
TI  - Hepatic radioembolization complicated by gastrointestinal ulceration.
AB  - Gastric ulceration is a relatively uncommon but well-described complication of
      yttrium 90 (Y90) radioembolization therapy in the locoregional treatment of
      hepatic tumors. Meticulous attention to vascular anatomy, an assessment of
      antegrade hepatic arterial flow, and knowledge of the dynamic embolic effect of
      the chosen Y90 particulate at treatment are requirements to reduce the risk of
      nontarget embolization to gastrointestinal structures. Radiation-associated
      gastrointestinal ulceration is difficult to treat, and may be associated with
      gastrointestinal bleeding, bowel obstruction, and perforation. Surgical excision
      of the involved segment with bypass may be necessary. The increased use of coil
      embolization of at-risk vessels combined with administration of Y90 particulates
      with minimal embolic effect has reduced the incidence of radioembolization
      associated gastrointestinal ulceration.

PMID- 22654272
TI  - Hepatic radioembolization complicated by fulminant hepatic failure.
AB  - A 68-year-old man with a history of metastatic colorectal carcinoma underwent
      left hepatic lobectomy and right hepatic wedge resection as initial treatment of
      his metastatic disease. He subsequently underwent right lobar radioembolization
      for treatment of a segment 8 lesion. At 6 weeks postembolization, he developed
      hepatic dysfunction which rapidly progressed to fulminant liver failure. A liver
      biopsy revealed hepatic venous obstruction and fibrosis. The patient died 14
      weeks after radioembolization.

PMID- 22654274
TI  - Pleural tumor seeding following percutaneous cryoablation of hepatocellular
      carcinoma.
AB  - Numerous modalities for hepatic tumor ablation are currently used including
      ethanol injection, radiofrequency ablation (RFA), cryoablation, and microwave
      ablation. The results and complications of these various tumor ablation
      techniques have been reported extensively, with the most data existing for
      percutaneous RFA. One of the most serious complications from tumor ablation is
      the seeding of cancer cells along the ablation tract. The incidence and risk
      factors for tract seeding in RFA have been reported, but little information
      regarding this complication with other ablation modalities has been reported. We
      report a case of tumor seeding into the pleural space following percutaneous
      cryoablation of hepatocellular carcinoma (HCC).

PMID- 22654273
TI  - Hepatic arterial embolization complicated by acute cholecystitis.
AB  - Hepatic arterial embolization (HAE) is a treatment used in the management of
      primary and some metastatic hepatic tumors. Complications of HAE are similar to
      those seen in other treatments, particularly transcatheter arterial
      chemoembolization (TACE), but without the possibility for chemotherapy related
      side effects. Particle reflux into the cystic artery is generally clinically
      occult but gallbladder ischemia severe enough to require cholecystostomy tube
      placement can occur. The authors discuss the case of a patient who underwent HAE
      and subsequently required a cholecystostomy tube due to development of acute
      cholecystitis.

PMID- 22654275
TI  - Thoracic duct embolization.

PMID- 22654276
TI  - Systemic air embolism.

PMID- 22654277
TI  - Universal access to health care for all: exploring road map.

PMID- 22654278
TI  - Nexus of poverty, energy balance and health.
AB  - Since the inception of planning process in India, health planning was an integral
      component of socio-economic planning. Recommendations of several committees,
      policy documents and Millennium development goals were instrumental in
      development of impressive health infrastructure. Several anti-poverty and
      employment generation programmes were instituted to remove poverty. Spectacular
      achievements took place in terms of maternal and child health indicators and
      expectancy of life at birth. However, communicable diseases and undernutrition
      remain cause of serious concern and non-communicable diseases are imposing
      unprecedented challenge to planners and policy makers. Estimates of poverty based
      on different criteria point that it has remained a sustained problem in the
      country and emphasizes on revisiting anti-poverty programmes, economic policies
      and social reforms. Poverty affects purchasing power and thereby, food
      consumption. Energy intake data has inherent limitations. It must be assessed in
      terms of energy expenditure. Energy balance has been least explored area of
      research. The studies conducted in three different representative population
      group of Eastern Uttar Pradesh revealed that 69.63% rural adolescent girls (10-19
      years), 79.9% rural reproductive age group females and 62.3% rural geriatric
      subjects were in negative energy balance. Negative energy balance was
      significantly less in adolescent girls belonging to high SES (51.37%), having
      main occupation of family as business (55.3%), and highest per capita income
      group (57.1%) with respect to their corresponding sub-categories. In case of
      rural reproductive age groups, this was maximum (93.0%) in SC/ST category and
      least (65.7%) in upper caste group. In case of geriatric group, higher adjusted
      Odd's Ratio for negative energy balance for subjects not cared by family members
      (AOR 23.43, CI 3.93-139.56), not kept money (AOR 5.27, CI 1.58-17.56), belonging
      to lower and upper middle SES by Udai Pareekh Classification (AOR 3.73, CI 1.22
      11.41), with lowest per capita income (AOR 15.14, CI 2.44-94.14) and in age group
      >80 years (AOR 5.76, CI 1.03-32.39). Of those in negative energy balance, 70.21%
      rural adolescent girls and 7 out of 10 geriatric subjects (activity based) were
      victims of CED. Extent of undernutrition and CED in rural reproductive age group
      females were more in those caste groups where energy deficit was also of higher
      magnitude. Energy balance must be visualized giving due consideration to the
      importance of exercise on human health. The evidence thus generated needs to be
      translated to the masses based on principles of translational research.

PMID- 22654279
TI  - Protein conjugate polysaccharide vaccines: challenges in development and global
      implementation.
AB  - Pneumonia and meningitis caused by Haemophilus influenzae type b, Streptococcus
      pneumoniae, and Neisseria meningitidis are among the leading causes of under five
      mortality and morbidity. Polysaccharide vaccines to prevent these infections are
      available since 1980s, but these are not effective in infants and children who
      are the common targets; therefore, protein conjugated were developed. The aim of
      this article is to understand the need for peumococcal protein conjugate
      vaccines, the challenges related to their development and global implementation,
      and the impact of these vaccines on global child health. Challenges in
      development of new vaccines are as follows:While pneumonia is a major threat in
      developing countries, available vaccine 7-valent pneumococcal conjugate vaccine
      (PCV7) protects against only 30% of invasive disease.Serogroup B of Neisseria
      meningitidis causes 32% of the cases in the USA and 45-80% or more in Europe. Due
      to similarity of its capsular polysaccharide with the cell surface glycoprotein
      on fetal brain tissue, developing a vaccine against this bacterium remains a
      challenge.Challenges in implementation are as follows:Replacement by nonvaccine
      serotypes;capsule switching;time duration of the antibody protective effect
      following vaccination;costs of the vaccines, programme costs, lack of knowledge
      of the disease burden, and targeting population groups for vaccination.

PMID- 22654280
TI  - Institutionalization of the NACP and Way Ahead.
AB  - In India, HIV prevention and control activities started way before the reporting
      of the first case of HIV infection. On reporting of evidences of HIV infection
      from different parts of the country and varied groups, Government launched the
      National AIDS Control Program (NACP). The program was launched on the foundation
      of early interventions and Mid-Term Plan, which evolved in three phases over the
      period of eighteen years. With progression of time, epidemiological situation
      changed and knowledge/capacity to tackle HIV improved. In the course of the
      evolution, NACP has moved from the centrally controlled program to district
      driven. Also different strategies were inducted/refined and many important
      institutes like Task Force, a high-powered National AIDS Committee, National AIDS
      Control Board, National AIDS Control Organization, State AIDS Control Societies,
      Project Support Units/Project Management Units, National Council on AIDS,
      Department of AIDS Control, Technical Support Unit, District AIDS Prevention and
      Control Unit (DAPCU) were created. Currently program is implemented vertically
      with good impetus and is able to contain the spread of HIV in India. For
      enhancing the effectiveness and sustainability, future of the NACP is strongly
      linked with the well-performing DAPCU and good synergy/integration with General
      Health System. HIV/AIDS epidemic in India has entered into the third decade.
      Evidences show that this epidemic in India is of concentrated type and
      characterized by the heterogeneity, following the type 4 pattern, where the
      epidemic shifts from the most vulnerable populations [such as female sex workers,
      men who have sex with men, injecting drug users to bridge populations (clients of
      sex workers, sexually transmitted infection patients, partners of drug users,
      long route truck drivers, short stay cyclical single male migrants], then to the
      general population and from urban centers to rural areas (ruralization of
      epidemic) with increasing involvement of youth and women (feminization of
      epidemic).

PMID- 22654281
TI  - Estimating the Burden of Disease from Unsafe Injections in India: A Cost-benefit
      Assessment of the Auto-disable Syringe in a Country with Low Blood-borne Virus
      Prevalence.
AB  - BACKGROUND: Unsafe medical injections are a prevalent risk factor for viral
      hepatitis and HIV in India. OBJECTIVES: This review undertakes a cost-benefit
      assessment of the auto-disable syringe, now being introduced to prevent the
      spread of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus
      (HIV). MATERIALS AND METHODS: The World Health Organization methods for modeling
      the global burden of disease from unsafe medical injections are reproduced,
      correcting for the concentrated structure of the HIV epidemic in India. A
      systematic review of risk factor analyses in India that investigate injection
      risks is used in the uncertainty analysis. RESULTS: The median population
      attributable fraction for hepatitis B carriage associated with recent injections
      is 46%, the median fraction of hepatitis C infections attributed to unsafe
      medical injections is 38%, and the median fraction of incident HIV infections
      attributed to medical injections is 12% in India. The modeled incidence of blood
      borne viruses suggests that introducing the auto-disable syringe will impose an
      incremental cost of $46-48 per disability adjusted life year (DALY) averted. The
      epidemiological evidence suggests that the incremental cost of introducing the
      auto-disable syringe for all medical injections is between $39 and $79 per DALY
      averted. CONCLUSIONS: The auto-disable syringe is a cost-effective alternative to
      the reuse of syringes in a country with low prevalence of blood-borne viruses.

PMID- 22654282
TI  - Alcohol Use and STI among Men in India: Evidences from a National Household
      Survey.
AB  - BACKGROUND: Alcohol use has been found to correlate with risky sexual behavior as
      well as with sexually transmitted infections (STI) among populations with high
      risk behavior in India. OBJECTIVE: To examine the correlates of alcohol use and
      its association with STI among adult men in India. MATERIALS AND METHODS: Data
      from a national representative large-scale household sample survey in the country
      were used. It included information on sociodemographic characteristics and
      alcohol use as a part of substance use. Clinical as well laboratory testing was
      done to ascertain the STI. RESULTS: The overall STI prevalence among adult males
      was found to be 2.5% (95% confidence interval (CI): 1.9-3.1). Over 26% adult men
      were found to have been using alcohol in the study population. It was higher
      among men who were illiterate and unskilled industrial workers/drivers. The men
      who consumed alcohol had higher prevalence of STI (3.6%; 95% CI: 2.9-5.1) than
      those who did not consume alcohol (2.1%; 95% CI: 1.5-2.6). The degree of
      association between alcoholism and STI was slightly reduced after adjusting for
      various sociodemographic characteristics (adjusted odds ratio: 1.5; 95% CI: 0.9
      2.3; P=0.06). CONCLUSIONS: The findings of present study suggest integrating
      alcohol risk reduction into STI/HIV prevention programmes.

PMID- 22654283
TI  - Mass drug administration coverage evaluation survey for lymphatic filariasis in
      bagalkot and gulbarga districts.
AB  - BACKGROUND: Lymphatic filariasis (LF) is endemic in 83 countries and territories,
      with more than a billion people at risk of infection. In view with the global
      elimination, mass drug administration (MDA) with single dose of
      diethylcarbamazine and albendazole tablets was carried out for the eligible
      population in Bagalkot and Gulbarga districts. OBJECTIVE: Assess coverage of MDA
      against LF in Bagalkot and Gulbarga districts. MATERIALS AND METHODS: In this
      cross-sectional coverage evaluation survey, one urban and three rural clusters
      were selected randomly in each district. The data were collected in a pretested
      performa, computed and analyzed using SPSS-10 to calculate frequencies and
      proportions. RESULTS: A total of eight clusters in two districts resulted in a
      total study population of 1,228 individuals. The overall compliance rate in
      Bagalkot district was 78.6% and in Gulbarga district it was only 38.8%. The prime
      reason for noncompliance was fear of side effects and not received tablets.
      CONCLUSION: There is an urgent need for more effective drug delivery strategies
      to improve the compliance in both the districts.

PMID- 22654284
TI  - A study to evaluate the effect of nutritional intervention measures on admitted
      children in selected nutrition rehabilitation centers of indore and ujjain
      divisions of the state of madhya pradesh (India).
AB  - BACKGROUND: The state of Madhya Pradesh has 1.3 million severely malnourished
      children. Nutrition rehabilitation centers (NRCs) were started in the state to
      control severe malnutrition and decrease the prevalence of severe malnourished
      children to less than 1% among children aged 1-5 years. MATERIALS AND METHODS:
      The present study was conducted from November 2008 to October 2009; 100 children
      admitted to seven different NRCs in Indore and Ujjain divisions of Madhya Pradesh
      were observed during their stay at NRCs and the follow-up period to analyze the
      effect of interventional measures on select anthropometric indicators. Mothers of
      the children were interviewed on health issues and therapeutic feeding practices
      at the NRCs using a predesigned and pretested interview schedule. RESULTS: The
      study group consisted of 48 boys and 52 girls; 60% were between 13 and 36 months
      of age. 93 children were analyzed for anthropometric indicators following a
      dropout rate of 7%. A statistically significant difference was obtained between
      the weight of children at admission and discharge (t=14.552, P<0.001); difference
      of mid upper arm circumference (MUAC) at admission and discharge was
      statistically significant (t=9.548, P<0.001). The average weight gain during the
      stay at the centers was 9.25 +/- 5.89 g/kg/day. Though the number of severe
      malnourished children decreased from 85 to 43 following the stay at NRCs (chi(2)
      = 44.195, P<0.001); 48.78% of the children lost weight within 15 days of
      discharge from the NRCs. Dropout rates of 9.89%, 23.07%, 42.65%, and 61.76% for
      the study group were obtained during the follow-up period of 6 months for the
      four follow-up visits conducted 15 days, 1, 3, and 6 months after discharge. The
      mothers of the children lacked adequate information on health issues and
      composition and preparation of therapeutic diets at the centers. CONCLUSION: The
      NRCs were effective in improving the condition of admitted children, but the
      effects were not sustained following discharge due to high drop-out rate and lack
      of adequate parental awareness. There is an urgent need to link these centers
      with community-based models for follow-up and improve health education measures
      to maintain the gains achieved.

PMID- 22654285
TI  - An epidemiological study of mental disorders at pune, maharashtra.
AB  - BACKGROUND: The WHO Global Burden of Disease study estimates that mental and
      addictive disorders are among the most burdensome in the world, and their burden
      will increase over the next decades. The mental and behavioral disorders account
      for about 12% of the global burden of disease. However, these estimates and
      projections are based largely on literature review rather than cross-national
      epidemiological surveys. In India, little is known about the extent, severity and
      unmet need of treatment mental disorders. Thus, there was a need to carry out
      rigorously implemented general population surveys that estimate the prevalence of
      mental disorders among urban population at Pune, Maharashtra. The study attempted
      to address unmet need and to form a basis for formulating the mental health need
      of the community. OBJECTIVE: The study was undertaken to estimate the lifetime
      prevalence and 12 month prevalence of specific mental disorders in urban
      population, socio-demographic correlates of mental disorders and to assess the
      service utilization in individuals with mental disorders. MATERIALS AND METHODS:
      The study was undertaken among adults aged 18 years and above living in house
      hold and in geographical area of Pune , Maharashtra. A minimum sample of 3000
      completed interviews was planned using representative probabilities to population
      size (PPS) sampling method which ensured equal probability for every eligible
      member. Data listing was obtained from Census Office from recent census of 2001
      data. The face to face interviews were undertaken in homes using fully structured
      interview schedule of World Mental Health Survey Initiative duly revised Version
      of WHO- Composite International Diagnostic Interview (CIDI 3.0) by trained
      investigators. Clinical reappraisal was carried out using Schedules for Clinical
      Assessment in Neuropsychiatry (SCAN) among ten percent of diagnosed cases
      selected randomly. Data were entered into DDE (Blaize Software) and analyzed
      using SPSS software package. RESULTS: Overall lifetime prevalence of mental
      disorders was found to be 5.03%.Rates among males (5.30%) were higher as compared
      to females (4.73%). Among the diagnostic group , depression(3.14%) was most
      prevalent followed by substance use disorder (1.39%) and panic disorder (0.86%).
      Overall 12 month prevalence of mental disorder was found to be 3.18% which was
      3.47% among males and 2.85% among females. Prevalence of depression (1.75%) was
      the most 12-month mental disorder, followed by substance use mental disorder
      (0.99%) and panic disorder (0.69%).Lifetime and twelve month prevalence of any
      mental disorder was the highest among employed group, followed by home makers and
      depression was more among married, followed by separated/divorced/widowed group
      and the least in unmarried group in the study. Treatment gap due to low
      prescription received indicated the most of the ill person did not acknowledge
      their need for treatment or do not received the appropriate care. CONCLUSION: The
      figure of 5.03% prevalence of diagnosable psychiatric disorders in adult
      population points to the great need to increase the prevention strategies both at
      primary and secondary level to overcome the disability and economic loss to
      society due to mental disorders.

PMID- 22654286
TI  - Impact of policy initiatives on civil registration system in haryana.
AB  - BACKGROUND: Despite the existence of Registration of Birth and Death Act (1969),
      Civil Registration System (CRS) in India registered only 68.3% of the births and
      63.2% of the deaths. Hence, National Population Policy (2000) emphasized the need
      to improve registration of vital events. In 2005, Haryana initiated policy
      changes to enhance registration of vital events. We evaluated the impact of these
      policy changes on CRS in 2009. MATERIALS AND METHODS: Records and reports of CRS
      were reviewed. On the basis of the birth and deaths reported by the Sample
      Registration System, the proportion of births and deaths registered by CRS were
      estimated using the projected population from 2001 Census. RESULTS: Before 2005,
      Police Stations were the registration centers in rural Haryana. On 1(st) January
      2005, the birth and death registration was made the responsibility of Primary
      Health Centers (PHCs). Medical Officers at PHCs were designated as Registrar and
      Pharmacists as Sub-Registrar of Births and Deaths. Auxiliary Nurse Midwife and
      Anganwadi Workers facilitated the registration. Till 2004, the registration of
      births was stagnant at the level of 70% for several years, which increased to 95%
      by 2009. Similarly registration of death events increased from 73.5% to 92.1%.
      CONCLUSION: Haryana state is still to achieve complete registration of births and
      deaths, but certainly shift of registration from police to health department has
      strengthened the CRS.

PMID- 22654287
TI  - Factors affecting the performance of undergraduate medical students: a
      perspective.
AB  - CONTEXT: Performance of medical students in developing nations like India is
      perceived to have largely declined. AIMS: We attempted to assess the reasons
      behind such trends. SETTINGS AND DESIGN: Students in their third year of medical
      study were given a predesigned, pretested structured and validated questionnaire
      that they filled in anonymously. The key areas assessed were concentration,
      interest and understanding of the subject and other perceived causes of poor
      performance. Tests for descriptive statistics were applied for evaluation.
      RESULTS AND CONCLUSIONS: One hundred and fifty students participated in the
      study. Fifty-five (36.66%) students performed poorly. Male gender, inability to
      clear the previous professional examination at the first attempt, difficulty in
      understanding medium of instruction, self-assessed depression, sleep disorders
      and perceived parental and peer pressure and dissatisfaction with career choice
      were significantly linked with poor performance (P<0.05 for each factor).
      Socioeconomic status and regularity in class were not linked to academic
      performance.

PMID- 22654288
TI  - Perceptions of Medical Students about their Educational Environment in Community
      Medicine in a Medical College of Coastal Karnataka.

PMID- 22654289
TI  - Association of adiposity with pulse pressure amongst gujarati Indian adolescents.

PMID- 22654290
TI  - H1N1 Newer Vaccine Usage: Experiences from Karnataka State.

PMID- 22654291
TI  - Different routes of administration of cell culture rabies vaccines.

PMID- 22654292
TI  - The current seroprevalence of hepatitis C virus in a tertiary care centre in
      vellore, Tamil Nadu.

PMID- 22654294
TI  - Blood transfusion transmitted infections in multiple blood transfused patients of
      Beta thalassaemia.
AB  - Transfusion Transmitted Infection (TTI) continue to be a problem in many parts of
      world and multi-transfused patients of beta thalassaemia major are at a
      particularly increased risk of TTI. This study is aimed to estimate the
      prevalence of blood TTI in multiple blood transfused patients of beta
      thalassaemia major. Cross-sectional study of 200 multi-transfused patients of
      beta thalassaemia major, who were interviewed using a structured questionnaire
      and history was taken regarding sero-status of HIV (Human Immunodeficiency
      Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus) infection from their
      case papers. This study was conducted at the department of Pathology, M.P. Shah
      medical college, Jamnagar and Thalassemia ward, G.G. Hospital, Jamnagar (Gujarat,
      India) from March to May 2010. Out of 200 multiple blood transfused patients 7%
      patients were infected with TTI. Total 9 male patients and 5 female patients were
      infected with TTI. The seroreactivity for HIV was 3% (06/200); 1% (02/200) were
      males and 2% (04/200) were females. The seroreactivity for HBV was 2% (04/200)
      all were males. The seroreactivity for HCV was 2% (04/200); 1.5% (03/200) were
      males and 0.5% (01/200) was female. HIV, HBV, HCV infections are most prevalent
      TTI among multiple blood transfused patients of beta thalassemia major, and
      remains a major health problem for these patients.

PMID- 22654293
TI  - Haematology research in India: past, present and future.
AB  - Haematology research in India is relatively recent in origin. However the
      pioneers in the field not only did exemplary work when compared to advanced
      western countries, they also made it a point to develop centres of excellence and
      human resources for future of haematology work in this country. In this brief
      overview an effort has been made to give a taste of quality and expanse of
      haematology research in this country. This review does not claim to have
      described every bit of haematology research in this country. Our pioneers worked
      under extremely difficult and trying circumstances on a subject which was limited
      to funding available from Indian Council of Medical Research. Now the times have
      changed, several funding agencies in the country are able to provide substantial
      fund for research. Modern state of the art basic research institutions are tying
      up with medical colleges for good quality research and the seeds which our
      pioneers had planted have grown into a mighty tree. It would not be an
      exaggeration to say we are on the threshold of the golden era of haematology
      research in this country.

PMID- 22654295
TI  - Unfurling the rationale use of platelet transfusion in dengue Fever.
AB  - Dengue fever and dengue haemorrhagic fever have emerged as a global public health
      problem in recent decades. The practice of platelet transfusion has been adapted
      into the standard clinical practice in management of hospitalized dengue
      patients. The exact indications and situations in which platelet have to be
      transfused may vary greatly. Blood components especially platelet concentrates
      due to their short shelf life are frequently in limited supply. Hence,
      appropriate use of blood is required to ensure the availability of blood for
      patients in whom it is really indicated, as well as to avoid unnecessary exposure
      of the patients to the risk of transfusion reactions and transmission of blood
      borne infection. The present study was conducted to evaluate the appropriateness
      of platelet transfusion done in dengue patients with thrombocytopenia. The
      present study was conducted on 343 serologically confirmed dengue patients
      admitted at JSS University Hospital between 1st January and 30th August 2009.
      Clinical data, platelet count and platelet requirements were analyzed. Among the
      343 serologically confirmed cases, the prevalence of thrombocytopenia (platelet
      count < 100,000/cumm) was 64.72% (222 patients) and bleeding manifestations were
      recorded in 6.12% (21 patients). 71 (20.7%) patients of dengue cases received
      platelet transfusion. Among them 34 (47.89%) patients had a platelet count
      <20,000/cumm, 28 patients (39.44%) had platelet counts in the range of 21
      40,000/cumm while the remaining 9 (12.67%) patients had platelet count between 41
      100,000/cumm. Out of 37 patients with a platelet count >20,000/cumm 11 patients
      had haemorrhagic manifestations such as petechiae, gum bleeding, epistaxis etc.,
      which necessitates the use of platelet transfusion. However, the remaining 26
      patients with platelet count >20,000/cumm and with no haemorrhagic manifestations
      received inappropriate platelet transfusion. Transfusion of 36.62% of platelet
      concentrate was inappropriate. The study emphasizes the need for development of
      specific guidelines for transfusion of blood components, constant interaction and
      co-ordination amongst clinicians and transfusion centre for implementation of
      these guidelines and a regular medical audit to review the optimal utilization of
      blood components.

PMID- 22654296
TI  - Iron profile in children with behavioural disorders: a prospective study in a
      tertiary care hospital in north India.
AB  - Iron deficiency anemia is the most frequent micronutrient deficiency in the
      developing countries like India especially affecting pregnant women and young
      children. Iron is an essential element involved in myelin formation,
      neurotransmitter synthesis and neuro-metabolism. Several behavioural disturbances
      have been reported in iron deficient children. In the present study, we
      determined the prevalence of iron deficiency anemia in children with behavioural
      disorders and assessed the improvement in terms of symptoms (by child behaviour
      check list), haematological parameters and iron status after treatment with oral
      iron. In this prospective study, 44 children in the age group of 3-12 years who
      were diagnosed with behavioural disorders were evaluated. Complete blood counts
      using automated hematology analyzer and iron parameters (serum iron, total iron
      binding capacity, % transferrin saturation and serum ferritin) were measured in
      all the patients to assess the prevalence of iron deficiency in these children.
      Thirty age matched controls were also studied. Iron deficiency was found in 32
      (73%) children, as assessed by transferrin saturation <16% and/or serum ferritin
      <16 MUg/l. Following treatment with iron for 100 +/- 10 days, there was a
      statistically (P <= 0.05) significant improvement in the clinical features,
      haematological profile and iron status. The presence of iron deficiency in
      children with behavioural disorders and subsequent improvement in clinical
      features, haematological profile and iron status suggests a possible causal
      relationship between iron deficiency and behavioural disorders.

PMID- 22654297
TI  - Neutrophil Apoptosis in Neutropenic Patients With Hepatitis C Infection: Role of
      Caspases 3, 10, and GM-CSF.
AB  - Patients with chronic HCV infection are prone to increased susceptibility
      bacterial infection due to neutropenia complicating the course of this disease.
      Neutropenia in those patients may stem from enhanced neutrophil apoptosis.
      However, the molecular mechanism of neutrophil apoptosis has not been clearly
      defined. Neutrophils harvested from 26 neutropenic patients with hepatitis C
      infection and nine age and sex-matched healthy control subjects were examined for
      the degree of apoptosis. Neutrophil apoptosis was quantified by flow cytometry
      through determination of annexin-V expression at 0 time (fresh neutrophil), and
      24 h culture. Neutrophils from healthy subjects were also incubated with either
      10% heterologous normal or neutropenic sera, with and without 10 ug GM-CSF.
      Caspases 3, 10 were assessed colormetrically in neutrophils at 0 times and after
      24 h culture. At 0 time culture the neutrophil apoptosis of the HCV patients was
      in significantly higher as compared to that of normal control (P = 0.059). At 24
      h culture patients neutrophils cultured with neutropenic patients own sera showed
      neutrophil apoptosis significantly increased as compared to that at 0 time
      culture and this effect was significantly attenuated in similar culture with
      addition of GM-CSF (P < 0.001). On the other hand patient's neutrophil cultured
      with normal sera showed insignificantly increased neutrophil apoptosis at 24 h
      culture as compared to that at 0 time culture. Caspases 3 and 10 activities were
      significantly higher in patients neutrophil after 24 h cultured with patients own
      sera as compared to 0 time culture (P < 0.001 for both). Addition of GM-CSF to
      the neutrophil culture down regulates the caspases 3 and 10 activities. The
      correlation study between annexin-V expression and caspases activities revealed a
      borderline positive correlation between annexin-V and caspase 3 (r = 0.376, P =
      0.058), and significant positive correlation with caspase 10 activity (r = 0.494,
      P = 0.01). In conclusion, these findings suggest that enhanced neutrophil
      apoptosis demonstrated in neutropenic patients with HCV infection might be
      induced through activation of caspase 10 and is attenuated by GM-CSF.

PMID- 22654298
TI  - Hematological Evaluation of Primary Extra Nodal Versus Nodal NHL: A Study from
      North India.
AB  - Primary extra nodal lymphomas (EN-NHL) are different from primary nodal non
      Hodgkin's lymphoma (N-NHL) and are comparatively less common. Hemogram findings
      and bone marrow involvement is less studied and very few reports are available in
      the literature. The present study is a retrospective analysis of bone marrow
      samples evaluated for staging of non-Hodgkin's lymphoma. The age, sex
      distribution, clinical features, and site of presentation, hemogram findings,
      pattern of bone marrow involvement and grade of reticulin fibrosis was noted.
      These findings were compared with the type of non-Hodgkin's lymphoma and
      prognostic information was determined. A total of 647 cases of NHL, which
      underwent bone marrow examination for staging, over a seven year period, were
      retrieved and analyzed for all hematological parameters. Prevalence of EN-NHL was
      23.5% (152/647), while nodal NHL comprised 76.5% (495/647) of all NHL cases.
      90.1% (137/152) cases of EN-NHL were adult patients, out of which 15.3% (21/137)
      cases showed bone marrow infiltration as compared to 89% (441/495) adult primary
      nodal NHL cases, of which 39% (175/441) showed bone marrow infiltration. 9.9%
      (15/152) cases of EN-NHL were pediatric patients, out of which 40% (6/15) showed
      bone marrow infiltration, while 10.9% (54/495) of nodal NHL cases were pediatric,
      of which 20.3% (11/54) showed bone marrow infiltration. Hemogram findings were
      not found useful in predicting bone marrow infiltration in both nodal as well as
      EN-NHL. 100% (6/6) of pediatric patients had high grade lymphoma as compared to
      48% (9/21) of adult patients, showing bone marrow infiltration in EN-NHL group.
      Reticulin fibrosis also did not reveal relation with grading of NHL.
      Prognostically EN-NHL of stomach and central nervous system were found to be
      better than EN-NHL of other sites, as none of these cases showed bone marrow
      infiltration. EN-NHL can involve various sites and the prognosis depends upon the
      sites of disease as well as the type of NHL. Moreover, pediatric EN-NHL cases are
      likely to have poorer prognosis, due to increased risk of bone marrow involvement
      as compared to their counterparts having primary nodal NHL. Bone marrow
      infiltration at times cannot be assessed reliably from hemogram findings only and
      a bone marrow biopsy for staging is mandatory.

PMID- 22654299
TI  - Metastasis of solid tumors in bone marrow: a study from northern India.
AB  - The metastasis of bone marrow by the solid tumors is a sign of advanced stage of
      disease and poor prognosis. The aim of this study was to assess the pattern of
      bone marrow involvement of different solid tumors and their correlation with
      hematological findings. In a retrospective study we evaluated 434 aspirates and
      76 biopsy sections from 124 cases of different types of solid tumors previously
      diagnosed on the basis of their clinical and histopathological findings. The
      hematological profile of the patients was done and correlated with the bone
      marrow findings. The study was carried out at a medical college hospital of
      northern India. Out of 124 cases of solid tumors 31 (25%) have metastasized to
      bone marrow. The highest number 25 (36%) of bone marrow involvement was seen in
      carcinoma prostate followed by gastric carcinoma and melanoma (25%) The least
      number (14.2%) cases of bone marrow metastasis were observed in endometrial
      carcinoma. Anemia was found the commonest (71.4%) hematological finding followed
      by thrombocytopenia in 45.1% cases. The bone marrow examination is an easy,
      convenient, sensitive and cost effective procedure for assessment of staging and
      monitoring of prognosis of solid tumors.

PMID- 22654300
TI  - Uric Acid as a potential biomarker of pulmonary arterial hypertension in patients
      with sickle cell disease.
AB  - Serum uric acid (UA) is emerging as a strong and independent marker for pulmonary
      arterial hypertension (PAH). PAH is well recognized as a life threatening
      complication of sickle cell disease (SCD). However, the association between UA
      and PAH in SCD is unknown. We reviewed electronic medical records (EMR) of 559
      consecutive adult SCD patients from Kings County Hospital Center (KCHC) between
      January 2005 and February 2010. Patients (n = 96) with measurement of UA in close
      temporal proximity to the transthoracic echocardiography (TTE) were identified.
      PAH was defined as pulmonary artery systolic pressure (PASP) >=30 mm Hg. Patients
      (n = 16) with other risk factors which may cause PAH and chronic renal
      insufficiency were excluded. In 18 patients, TTE could not measure PASP. Finally,
      62 patients were selected. Statistical analysis was performed using Student t
      tests, Pearson correlation coefficient and multivariate regression analysis. Out
      of 62 patients, 30 had PAH. Patients with PAH had a higher UA level (8.67 +/- 4.8
      vs. 5.35 +/- 2.1, P = 0.001). We found strong positive correlation between the UA
      level and PASP (r = 0.71; P < 0.0001). This correlation was independent of
      diuretic use. UA could be a potential marker for PAH in SCD. However, its'
      prognostic and pathophysiologic role in SCD patients with PAH needs to be further
      investigated.

PMID- 22654301
TI  - Autoimmune lymphoproliferative syndrome: response to mycophenolate mofetil and
      pyrimethamine/sulfadoxine in a 5-year-old child.
AB  - Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of
      disrupted lymphocyte homeostasis characterized by chronic splenomegaly and
      lymphadenopathy of early onset, hypergammaglobulinemia (Ig G and Ig A),
      autoimmune phenomena, and expanded populations of TCR-alpha/beta+, CD3+, CD4-,
      CD8-T cells (Fisher et al. Cell 81:935-946; 1995), called double negative T-cells
      [(DN) T cells]. We discuss a case of ALPS which showed good response to
      immunosuppressant drug Mycophenolate-Mofetil in combination with
      Pyrimethamine/Sulfadoxine.

PMID- 22654302
TI  - Exflagellated microgametes of Plasmodium vivax in human peripheral blood: an
      uncommon feature of malaria.
AB  - In the life cycle of malarial parasite exflagellation of microgametes occur in
      mosquitoes. Usually this will not occur in the peripheral blood of human beings.
      However, exflagellation can occur in the collected blood and may create
      diagnostic dilemma. We report a case of vivax malaria with exflagellated
      microgametes, which were mistaken for a double infection of vivax malaria and
      borrelia.

PMID- 22654303
TI  - Autoimmune hemolytic anemia: mixed type-a case report.
AB  - Mixed autoimmune haemolytic anemia (AIHA) is defined by the presence of both warm
      and cold auto antibodies. Diagnosis is based on detection of autoantibodies by
      monospecific direct antiglobulin test showing a pattern of IgG and complement C3d
      and presence of cold agglutinins. We report a rare case of primary mixed AIHA in
      a 12 year old girl who responded to corticosteroids.

PMID- 22654304
TI  - Acute lymphoblastic leukaemia with microfilaria: a rare coincidence in bone
      marrow aspirate.
AB  - Microfilariae in bone marrow aspirates have been reported occasionally, but until
      now no case has been reported in association with acute leukaemia. This is a
      unique finding, not mentioned in literature. Microfilariae are seen mainly in
      peripheral blood smears (PBS) and rarely in bone marrow aspirate, but this
      surprisingly did not show any parasite in PBS. Meticulous examination of bone
      marrow smears revealed acute lymphoblastic leukaemia and a few interspersed
      microfilariae. This rare combination, reported for the first time, definitely
      needs a space in literature.

PMID- 22654305
TI  - Glanzmann's Thrombasthenia: A Rare Cause of Recurrent Profuse Epistaxis.
AB  - Though epistaxis is a commonplace emergency encountered in the
      Otorhinolaryngology clinic, recurrent, severe and intractable cases are
      relatively less common. In those cases where no local causes are found that could
      explain such episodes, systemic causes, including hematological disorders should
      be considered, and thoroughly explored. However, routine hematological
      investigations often fail to identify a definite cause. Here we report about a 23
      year-old woman presenting with severe recurrent epistaxis due to Glanzmann's
      thrombasthenia-a rare, autosomal recessive disease. Never before Glanzmann's
      thrombasthenia has been reported to present with severe epistaxis as its sole
      feature.

PMID- 22654306
TI  - Hemophagocytosis associated with hepatitis a and e coinfection in a young child.
AB  - We report and discuss a unique case of hemophagocytosis associated with hepatitis
      A and E coinfection in a young child which has never been reported earlier in
      children. Its varied presentation is emphasized and possible management options
      and outcome are discussed.

PMID- 22654307
TI  - Immunoglobulin and iron deficiency anemia.

PMID- 22654308
TI  - Epizootiology, pathogenesis and immunoprophylactic trends to control tropical
      bubaline fasciolosis: an overview.
AB  - On the Indian sub-continent, nearly 5,000 years ago, the domestication of the
      riverine buffalo-the incredible Asian dairy animal was initiated. It plays a
      versatile role in socio-economic upliftment of its owners from the rural
      agricultural communities in Asian, African, South American and a few European
      countries. Comparatively, buffaloes are lesser evolved and susceptible to
      infectious diseases than cattle. However, poor body thermoregulation and
      wallowing nature predisposed them to snail borne infections, especially tropical
      fasciolosis-an incessant major constraint on buffalo production and improvement
      programmes. This review article is an insight into the global prevalence, varied
      epizootiological factors, offers possible explanation to pathophysiological
      clinical signs, deleterious effects of the tropical liver fluke, involving hepato
      biliary system, haemopoitic system, endocrine glands and their secretions,
      oxidative stress, altered metabolism and significant fall in food conversion
      efficiency with unaffected digestibility of nutrients. Besides, the authors have
      briefly discussed and reviewed the developments and significance of successful
      immunodiagnostic approaches for detecting and forecasting the disease during
      early pre-patency and feasibility of developing a cost effective immunoprotection
      strategies against tropical fasciolosis.

PMID- 22654310
TI  - Distribution pattern of apicomplexan parasites (Sporozoa: Haemosporida) in
      Columba livia, Gmelin.
AB  - During 39 months of sampling, the prevalence of apicomplexan parasites
      (Haemoproteus and Plasmodium) was studied in Columba livia Gmelin of Rohilkhand
      region, UP, India, according to the sex of the host, different seasons and host
      localities. Out of 266 pigeons sampled, 148 pigeons were positive for
      Haemoproteus at a prevalence of 55.63%. Only 18 pigeons (2.67%) had a dual
      Haemoproteus and Plasmodium infection and 130 pigeons (48.87%) had Haemoproteus
      infection. No pigeons were positive for Plasmodium alone. Parasite incidence in
      relation to the sex of the host indicated a higher infestation in females
      (62.79%) as compared to males (57.65%). The overall highest infectivity of
      parasites was recorded during the summer season (82.85%) followed by spring
      season (59.37%) and least in the winter season (42.30%). It was also observed
      that Haemoproteus occurred at diverse infectivity in C. livia from different
      localities (Badaun 51.35%, Bareilly 57.14%, and Shajahanpur 58.06%) whereas
      Plasmodium was recorded at 11.18% only from Bareilly. The intensity of the
      parasite was highest (2.77/100 RBC) at Shahjahanpur.

PMID- 22654309
TI  - Control of poultry coccidiosis: changing trends.
AB  - Coccidiosis is the most important protozoan disease affecting the poultry
      industry worldwide. Control of poultry coccidiosis is presently based on
      managerial skills and the use of prophylactic coccidiostatic drugs. With the
      emergence of drug resistant Eimeria strains, emphasis has been laid on
      development and use of safer vaccines; some of them have been commercialized
      successfully. The present review deals with the various factors responsible for
      the development of clinical coccidiosis in poultry as well as an overview of the
      currently available inducers and boosters of immunity against coccidiosis. There
      are three groups of vaccines currently available against coccidiosis which can be
      distinguished on the basis of characteristics of the Eimeria species included in
      the respective products, viz. vaccines based on live virulent strains, vaccines
      based on live attenuated strains, and vaccines based on live strains that are
      relatively tolerant to the ionophore compounds. The latter vaccine combines the
      early chemotherapeutic effect of ionophores with the late prophylactic effect of
      vaccination. Although in the near future more varieties of oocyst based live
      vaccines are expected, identification of selective coccidian-specific
      immunoprotective molecules is likely to get more attention to facilitate the
      sustainable control of poultry coccidiosis.

PMID- 22654311
TI  - Two new species of Myxobolus (Myxozoa: Myxosporea: Bivalvulida) infecting an
      Indian major carp in Ropar and Kanjali wetlands (Punjab).
AB  - In India, more than 104 species of Myxobolus are recorded infecting freshwater
      and marine fishes. During our study on the myxozoan parasites of fishes of Punjab
      wetlands, India, two new myxosporean species, Myxobolus ropari sp. nov. and
      Myxobolus kanjali sp. nov. were recorded from mucous membrane around gill
      lamellae and scales of Cirrhina mrigala (Ham.), respectively. Spores of the first
      species, M. ropari sp. nov. measure 12.58 * 4.5 MUm in size, elongately pyriform,
      slender in shape with a pointed anterior end and a rounded posterior end. Polar
      capsules are two, equal, elongately pyriform, measuring 4.96 * 1.50 MUm in size,
      placed posteriorly from the tip of the spore running parallel to each other.
      Spores of the second species, M. kanjali sp. nov. measure 9.5 * 7.7 MUm in size,
      spherical in shape with rounded anterior and posterior extremities. Polar
      capsules are two, equal, broadly pyriform with a blunt anterior and a rounded
      posterior end measuring 4.8 * 1.8 MUm in size. A prominent tubular structure
      originate from the anterior end of one of the polar capsule and extend backward
      beyond the margin of the spore body and run upwards to join the posterior end of
      the other polar capsule.

PMID- 22654312
TI  - Two new species of Myxobolus (Myxozoa:Myxosporea:Bivalvulida) from freshwater
      fishes of Punjab wetlands (India).
AB  - During the present study two new species were collected from mucous membrane
      around gill lamellae of Puntius sophore (Ham.) vern. chittal and Cirrhina mrigala
      (Ham.) vern. mrigal from Harike Wetland, Punjab respectively. Spore of the first
      species i.e. Myxobolus chittalii are histozoic, pear shaped with characteristic
      nipple-like anterior end and rounded posterior end. They measure 9.0 * 6.18 MUm.
      Polar capsules are two, equal, measuring 4.5 * 2.4 MUm, pyriform with bluntly
      pointed anterior end and rounded posterior end. They are placed posteriorly from
      the tip of the spore and are parallel to each other in the spore body cavity. A
      prominent, tongue shaped intercapsular process is present. Spores of the second
      species i.e. M. mehlhorni are histozoic, oval to egg in shape having narrow,
      blunt anterior end and broad rounded posterior end, measure 8.9 * 6.8 MUm. Shell
      valves smooth, symmetrically thin, measure 0.5 MUm in thickness. Parietal folds
      are absent. Polar capsules two, prominently unequal, placed anteriorly and
      converge towards the anterior end. Both polar capsules are flask-shaped with
      anterior end having a prominent neck. The larger polar capsule measure 3.7 * 2.5
      MUm occupying less than half while the smaller one measure 2.6 * 1.5 MUm and
      occupy less than one-third of the spore body cavity. An intercapsular process is
      absent.

PMID- 22654313
TI  - Three new species of Xiphidiocercariae from the thiarid snail Thiara tuberculata
      in Palakkad, Kerala, India.
AB  - Three new species of Xiphidiocercous cercariae, Cercaria sp. IX Malabar n.sp.,
      Cercaria sp. X Malabar n.sp. and Cercaria sp. XI Malabar n.sp. were recovered
      from the thiarid snail Thiara tuberculata collected from freshwater bodies in the
      Palakkad district of Kerala. The three new species are described in detail and
      compared with their related species to establish their systematic position.

PMID- 22654314
TI  - Natural trematode infection in liver of water buffalo (Bubalus bubalis):
      histopathological investigation.
AB  - This study reports the infection of liver and bile ducts, carried out from
      November 2008 to April 2010, on 730 randomly selected water buffaloes
      Bubalusbubalis, infected with the amphistome trematode parasite Explanatum
      explanatum (Creplin, 1847) Fukui, 1929. Macroscopic examination revealed massive
      infection of adult fluke in bile ducts and intrahepatic ductules in 131 (18%)
      cases. The predominant features were multifocal granulomatous nodules throughout
      the luminal surface of the bile ducts. Histopathological study of 4 MUm thick
      tissue sections cut adjacent to and through the site of attachment of individual
      worm and stained with hematoxylin and eosin revealed intense infiltration of
      inflammatory cells such as lymphocytes, macrophages, plasma cells, eosinophils as
      well as fibrocytes. This was associated with fibrosis and thickening of the bile
      ducts. Due to high level of prevalence and intensity of natural infection,
      amphistomiasis appears to be endemic in this geographical region and probably
      represent one of the most important animal health problems. It is hoped that the
      study may draw attention to the need for educating farmers, regarding the
      economic importance of infection of these amphistome parasites and also for the
      development of control strategies to prevent the spread of infection to
      ruminants.

PMID- 22654315
TI  - Intestinal coccidian parasitic infections in rural community in and around Loni,
      Maharashtra.
AB  - Fecal samples examination of 310 individuals with variable gastro-intestinal (GI)
      disturbances but negative for intestinal parasites or bacterial pathogens,
      revealed 97 persons positive for infection with coccidian parasites employing
      modified Ziehl-Neelsen (ZN) staining and Sheather's sucrose floatation technique.
      Cryptosporidium oocysts alone were detected in 64 (64/97; 66%) cases whereas
      Cyclospora oocysts along with Cryptosporidium were present in other 30 cases
      (31%); remaining three cases yielded only Cyclospora oocysts (3%) in their feces.
      None of the 97 cases positive for the two coccidian parasites was reactive for
      antibodies to human immunodeficiency virus (HIV) in their blood nor did any
      individual have history of taking immuno-suppressive drugs or antibiotics in the
      recent past. A breakdown of these 97 cases according to age and sex revealed not
      much difference in infection with two coccidian parasites. Further, comparison
      between two techniques revealed modified ZN staining was far superior to
      Sheather's floatation. As the coccidian parasites, particularly Cryptosporidium
      is gaining much importance; therefore modified ZN staining should be included
      preferably along with other techniques in routine fecal examination which may
      lead to an overall improvement in the health-care facilities.

PMID- 22654316
TI  - A study on in vitro culture of Trichuris ovis in different physiological
      solutions at constant temperature, 37 degrees C.
AB  - The primary aim of in vitro culture of whipworms (Trichuris ovis) is to provide
      artificial conditions under which the life cycle of the parasites completed
      outside the host under controlled conditions. The physiological solutions used
      for the present study were sodium chloride (0.64%), Ringer's solution, Tyrode's
      solution, and Lock-Lewis solution. Parasites were collected from freshly
      slaughtered intestine of the host. The recovered parasites were washed with
      running tap water after that with normal saline. After washing parasites were put
      in four petridishes containing different physiological solutions. Observations
      were recorded after interval of every 8 h. The hundred percent survival of
      Trichuris ovis was observed at 32, 40, and 48 h in NaCl (0.64%), Ringer's,
      Tyrode's, and Lock-Lewis solution, respectively in case of both male and female
      parasites. In sodium chloride solution (0.64%) cent percent mortality was
      observed after 64 h of incubation in males and in case of females it was observed
      72 h. In Ringer's solution cent percent mortality was observed after 72 in males
      and in females it was observed 80 h. In Tyrode's solution cent percent mortality
      was observed after 88 h in males and 96 h in females. In Lock-Lewis solution cent
      percent mortality was observed after 96 h in case of both the male and female
      parasites. Present study could be used to understand the effects of various drugs
      on the above parasites and also other intra-intestinal parasites.

PMID- 22654317
TI  - Seasonal incidence of protozoan parasites of the black tiger shrimp (Penaeus
      monodon) of Sundarbans, West Bengal, India.
AB  - There is a delicate balance between the host, pathogen and environment. Aquatic
      organisms, including shellfish, respond directly to climatic changes in their
      biological environment as their metabolic processes are influenced by
      temperature, salinity, and oxygen levels. Certain environmental conditions are
      more conducive to diseases than others among which water temperature is
      significantly associated with disease outbreak. The present study showed that
      Peneaus monodon of Sundarbans serve as a host for many protozoan parasites and
      epibionts including ciliates, gregarines and microsporidia. The protozoan
      parasites also require a particular environmental condition for their maximum
      growth and survival. The intensity of infection significantly increases with rise
      in temperature (P < 0.05) following a definite trend but no significant
      relationship between infection rate of ciliates and pH of water. In case of
      gregarine parasites significance (P < 0.05) exists among infection rate and
      temperature as well as pH of the farm water. Microsporidian parasites do not
      follow any significant seasonal trend in infecting the host P. monodon.

PMID- 22654318
TI  - Metazoan parasites of the Indian mackerel, Rastrelliger kanagurta (Scombridae) of
      Visakhapatnam coast, Bay of Bengal.
AB  - The metazoan parasite fauna of the Indian mackerel Rastrelliger kanagurta of
      Visakhapatnam coast, Bay of Bengal comprised 15 species including three species
      of Monogenea, seven species of Digenea and five species of Crustacea. Digeneans
      were the dominant members in the parasite spectrum while infections with
      ectoparasitic monogeneans and crustaceans were rare. The digeneans Opechona
      bacillaris and Lecithocladium angustiovum which occurred with high prevalence and
      mean intensity are the typical parasites of the mackerel. The parasitic fauna in
      general is found to be a reflection of the planktonivorous diet of the host.
      Except for two species of digeneans, Lecithocladium angustiovum and Aponurus
      laguncula, all the remaining species of metazoans showed narrow specificity to R.
      kanagurta, indicating a high degree of host specialization. The parasitological
      data may prove useful for differentiating stocks of R. kanagurta.

PMID- 22654319
TI  - Occurrence of Gnathostoma spinigerum in free range tigress.
AB  - Postmortem examination of free-range tigress of Pench Tiger Reserve, MP, India,
      aged approx 15 years revealed nodule in the pyloric part of the stomach packed
      with worms and was identified as Gnathostoma spinigerum on the basis of
      morphology of male and female worms, including eggs.

PMID- 22654320
TI  - Detection of filarial specific IgG4 antibodies in individuals residing in endemic
      areas using panLFRAPID test card.
AB  - In order to achieve the goal of global programme for elimination of lymphatic
      filariasis (GPELF), chemotherapy programmes are underway to interrupt
      transmission of the disease. At this point, detection of exposure will be more
      appropriate to monitor the programme and to certify areas cleared of active
      transmission as disease-free. A recently available cassette form of rapid test,
      panLFRAPID is a filarial IgG4 antibody detection test that may be useful for the
      programme. Therefore, we carried out a preliminary test using this cassette test
      on various categories of serum samples. The result showed that the test appeared
      to have potential in monitoring the exposure to filarial infection in GPELF.

PMID- 22654321
TI  - A new report on the occurrence of monogenean parasites (Monogenoidea) on gill
      filaments of freshwater fishes in Meghalaya.
AB  - The edible freshwater fishes of several genera including Labeo, Cyprinus,
      Cirrhinus, Danio, Puntius, Garra (Cypriniformes), Channa (Channiformes), Clarias,
      Heteropneustes, Rita, Monopterus, Ompak, Bagarius and Mystus (Siluriformes) in
      Meghalaya State were examined for their helminth parasite spectrum. Two
      monogenean flukes representing the genera Diplozoon and Bifurcohaptor were
      recovered from the gills of the host fish, which are redescribed herein and their
      descriptions supplemented with information on their surface fine topography.
      Labeo pangusia and L. boga constitute new host records for the diplozoid
      monogenean. Both the monogenean species are reported for the first time from the
      fishes in Meghalaya, a new locality record.

PMID- 22654323
TI  - Withering internship training in India.

PMID- 22654322
TI  - Accuracy of probing attachment levels using a new computerized cemento-enamel
      junction probe.
AB  - BACKGROUND AND OBJECTIVES: The assessment of clinical attachment level (CAL)
      represents the gold standard for diagnosing and monitoring periodontal disease.
      The aim of the present study was to evaluate the performance of the newly
      introduced cemento-enamel junction (CEJ) probe in detecting CAL, using CEJ as a
      fixed reference point, and to compare the CEJ probe with the Florida stent probe
      (FSP) as well as with a standard manual probe, University of North Carolina-15
      (UNC-15). MATERIALS AND METHODS: Three examiners recorded the probing attachment
      level in 384 sites in case group (chronic periodontitis), and in 176 sites, in
      control group (healthy periodontal status), using the three probes. Subjects
      included both the sexes and ranged from 35 to 45 years. The experimental design
      was structured to balance the intra- and inter-examiner consistency at the same
      site during the two visits. RESULTS: CEJ probe showed higher intra-and inter
      examiner consistency over both FSP and UNC-15 in both the case and control
      groups. Frequency distribution of differences of various magnitudes of repeated
      measurements <=1 mm was in the higher range of 86.8% to 87.5% for CEJ probe. The
      FSP was more reproducible than UNC-15 in detecting relative attachment level
      (RAL). INTERPRETATION AND CONCLUSION: CEJ automated probe was found to have
      greatest potential for accuracy and consistency in detecting CAL than FSP and UNC
      15. The automated probes appeared to be more reproducible than manual probes.

PMID- 22654324
TI  - Chernobyl & Fukushima: Lessons to be Learnt.

PMID- 22654325
TI  - Prospective randomised controlled trial comparing sub-epididymal orchiectomy
      versus conventional orchiectomy in metastatic carcinoma of prostate.
AB  - Androgen blockade (surgical or medical castration) is a standard procedure for
      patients with metastatic carcinoma prostate. Sub-epididymal orchiectomy involves
      removal of testis leaving behind epididymis. This epididymal stump over a period
      gives a pseudo testicular feel within the scrotum. We present a prospective
      randomized study to assess the functional utility of this procedure and compare
      it with total orchiectomy in terms of achieving castrate levels. From July 2005
      Jan 2008, 60 patients with metastatic carcinoma prostate were alternately
      randomised and allotted to two groups, 30 underwent sub-epididymal orchiectomy
      (group A) and remaining 30 (group B) underwent total orchiectomy. Age: 56-80
      years. Serum PSA: 55-268 ng/ml. Preoperative serum testosterone: Group A-300-650
      ng/ml and group B-320-640 ng/ml. Postoperative serum testosterone: group A-2-18
      ng?ml and group B-7-15 ng?ml on day 7 after surgery. Operating time-26-40 mins
      for group A and 20-34 mins for group B. Follow up-6 weeks and 3 months. At 3
      months patients were asked to grade appearance of scrotum for asthetic value on a
      scale of 1-100 using visual analogue score. Postoperative serum testosterone
      reached castrate levels in seven days (both groups). Duration of surgery in both
      groups was comparable. Complications-wound infection in 1 patient (group A) & 1
      scrotal hematoma (group B). Satisfaction score for group A (83.5 +/- 9.7) was
      significantly (p < 0.05) better (95%CI-18.58-28.42), compared to that of group B
      (60 +/- 9.4) by using't' test. Sub epididymal orchiectomy is comparable to total
      orchiectomy in terms of achieving castrate levels with similar operating time. It
      has significant advantage in terms of mental satisfaction to patients. It is a
      simple and safe procedure that can be conveniently performed in an outpatient
      clinic setting using pure local anaesthesia.

PMID- 22654326
TI  - Clinico-Microbiological Aspects of Necrotising Fasciitis in Type II Diabetes
      Mellitus.
AB  - Necrotising fasciitis is insidiously advancing soft tissue infection,
      characterized by widespread fascial necrosis. One of the most common conditions
      encountered in the clinical practice and which required clinical suspicion in
      patients who have less resistance to these infections. Especially in diabetic
      patients who are more prone for such infection due to low immunity and other
      reasons like early detection of these infections helps these patients to have a
      better recovery by aggressive surgical management and other measures required for
      the same. Literature has enough evidence on how serious this entity. Hence this
      study is designed in that aspect to help in early diagnosis and appropriate
      treatment. This study will help to determine the clinical presentation, the
      polymicrobial involved. The organisms most closely linked to necrotizing
      fasciitis are group A beta-hemolytic streptococci, although the disease may also
      be caused by other bacteria and their sensitivity patterns will help us to
      install appropriate antibiotics with the surgical management. And to compare our
      mortality rate with the other studies. A prospective descriptive study including
      all type II diabetic patients with necrotizing fasciitis over 3 years. Patients
      were evaluated in detail with respect to patient's history, examination, culture
      sensitivity and chart reviews and followed up using standard evaluation tools to
      measure the various outcomes. In 62 patients, the commonest clinical presentation
      was necrotic patch of skin and cellulites. The organisms cultured being beta
      hemolytic streptococci and E.Coli. The culture sensitivity pattern is to broad
      spectrum antibiotics. The average stay in the hospital was about 13.74 days for
      the study group and the time delay in presentation is 6 days. Wagner's score is a
      useful tool for aiding the diagnosis. Patients without foot care had extensive
      lesions. And a mortality rate of 1.6 % in these patients. In an acutely swollen
      limb in a diabetic patient a high degree of suspicion of necrotizing fasciitis is
      required. A detailed foot care is warranted in these patients. An early extensive
      debridement is mandatory and key for a favorable outcome. And to start on broad-
      spectrum antibiotics is advisable. Wagner's scoring is helpful to predict the
      chances of a second surgery. With the above entities in mind the mortality rate
      of necrotizing fasciitis in type ii diabetes mellitus can be contained.

PMID- 22654327
TI  - Doctor patient communication-a vital yet neglected entity in Indian medical
      education system.
AB  - Doctor patient communication is the most important and an integral part of any
      treatment regimen. Properly carried out it has been shown to have a therapeutic
      effect equivalent to drugs. Despite being so important part of treatment it is
      more than often taken and carried out casually. Apart from apathy towards this
      practice, its omission in the medical study curriculum is an important factor.
      This study was carried in amongst the surgical residents of surgical departments
      of various medical colleges to assess the attitude of surgical residents towards
      patient doctor communication. A questionnaire was forwarded by mail and email and
      the response was assessed: The responses of the surgical residents from various
      residents from different medical colleges were similar. Most of the residents
      prefer inclusion of communication skill in medical education curriculum.

PMID- 22654328
TI  - Giant retroperitoneal lipoma presenting as inguinal hernia.
AB  - Retroperitoneal lipomas are known for their rarity and varied presentations. We
      are reporting a case of giant retroperitoneal lipoma which presented as inguinal
      hernia.

PMID- 22654329
TI  - Role of prophylactic antibiotics in open inguinal hernia repair: a randomised
      study.
AB  - To study the role of prophylactic antibiotics in open inguinal hernia repair. A
      total of 200 patients were included, they were randomised in two groups. Group 1
      was given prophylactic dose of inj amoxy-clav while group 2 was given placebo
      only. Results were compared and Data analysed using the Chi-square test.
      Complications in both the groups were compared. Rate of serous discharge and
      seroma formation was 1% and 22% respectively in group 1 while 2% and 26% in group
      2 also the rate of erythema and stitch abscess were 1% and none in group 1 and 2%
      and 1% in group 2 respectively. On statistical analysis these differences were
      not significant. Addition of prophylactic antibiotics in elective open inguinal
      hernia repair has no significant benefit over placebo although larger studies are
      required to prepare some uniform guidelines.

PMID- 22654330
TI  - Surgeons' Evaluation of Colorectal Cancer Resections Against Standard HPE
      Protocol-Auditing the Surgeons.
AB  - The survival of Colorectal Cancer patients is very much dependent on complete
      tumor resection and multimodality adjuvant treatment. However, the main
      determinants for management plan of these patients rely heavily on accurate
      staging through histopathological examination (HPE). A reliable standard HPE
      protocol will be a significant impact in determining best surgical outcome. We
      evaluate surgeons' intra-operative judgment and the quality of resected specimens
      in the treatment of colorectal cancers. To quantify the quality of surgery by
      applying standard HPE protocol in colorectal cancer specimens and to assess the
      use of new format for pathological reporting in Colorectal Cancer using a
      formulated standard proforma. We perform a prospective observation of all
      colorectal cancer patients who underwent surgical resection over 8 month
      duration. Surgeons are required to make self-assessment about completion of tumor
      excision and possible lymph nodes or adjacent organ involvement while all
      pathologists followed standard reporting protocol for examination of the
      specimens. We evaluate the accuracy of surgeons judgment against HPE. The study
      involved 44 colorectal cancers comprising of 23 male and 21 female patients. The
      majority of these patients were Malay (50%) followed by Chinese (43%) and Indian
      (7%). The main presenting symptoms were bleeding (32%), intestinal obstruction
      (29%) and perforation (7%). Sixteen (36%) patients underwent emergency
      surgery.Rectal tumor was the commonest (53%) followed by sigmoid colon (22.7%).
      Neoadjuvant Chemoradiation were given to 8 patients and complete pathological
      response was observed in 1 (12.5%) of these. The final TNM classification for
      staging were; stage I (22.7%), stage IIa (18.2%), stage IIb (11.4%), stage IIIa
      (2.3%), stage IIIb (25%), stage IIIc (13.6%) and stage IV (6.8%).The commonest
      surgery performed was anterior resection with mesorectal excision (43.2%). Ten
      patients (22.7%) had laparoscopic surgery with 3 (30%) patients converted to open
      surgery. The surgeons claimed to have performed a curative resection with
      complete excision and clear margin in 40 (90%) patients. Of these, only 1 (2.5%)
      patient had a positive resection margin. Meanwhile, the surgeons reported
      involvement of resection margins in 4 cases but this was disputed by the HPE in
      all 4 cases. Lymph nodes involvement was detected intra-operatively in 13 (29.5%)
      of the cases and all were proven positive for metastases through HPE. On the
      other hand, of the remaining 31 patients who were reported as no obvious
      lymphadenopathy by the surgeons, lymph nodes positvity was found in 7 (22.5%)
      cases. Using standard HPE reporting protocol brings suitable evaluation of
      surgery in colorectal cancer treatment. Although surgeons' judgment is fairly
      accurate in predicting margin clearance and complete specimen excision, complete
      mesocolic and mesorectal excision is of utmost importance since lymph nodes
      metastatic involvement may not be obvious at surgery.

PMID- 22654331
TI  - Centchroman regresses mastalgia: a randomized comparison with danazol.
AB  - We conducted a randomized trial to evaluate effectiveness of Centchroman in
      control of mastalgia and compared it with Danazol. Research Question- Is
      proportion of pain relief achieved by Centchroman similar to or inferior to that
      achieved by Danazol? In a randomized controlled trial of Centchroman vs. Danazol
      in mastalgia, 81 patients with mastalgia were studied. Thirty-nine patients were
      randomized to Danazol arm and 42 in Centchroman arm. The treatment was given for
      12 weeks, followed by observation for 12 weeks. The pain was measured by visual
      analogue scale (VAS) of 0-10. At 12 weeks 89.7% women achieved reduction in pain
      score to <=3 in Centchroman group (pvalue 0.001). In Danazol group 69.44% women
      achieved reduction in pain score to <= 3 (p = 0.001). Three months after stopping
      therapy, Centchroman was more effective in pain score reduction at 24 weeks as
      compared to Danazol (p = 0.019). Centchroman is an effective, safe and
      inexpensive alternative to Danazol for treatment of mastalgia. ELECTRONIC
      SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12262
      010-0216-z) contains supplementary material, which is available to authorized
      users.

PMID- 22654332
TI  - Sacrococcygeal masses other than meningomyelocele.
AB  - This series comprises of a variety of sacrococcygeal masses other than
      meningomyelocele that presented to the department of pediatric surgery of Medical
      College Kolkata over last 10 years. In this series, 23 cases of sacrococcygeal
      masses are included. Barring meningomyelocele, teratoma constitutes a major group
      of cases. It also includes few other interesting and atypical masses such as
      presacral dermoid, degenerated nerve fiber, fibrofatty tissue, rhabdomyosarcoma,
      etc. This is an endeavor to enlighten ourselves so that the diagnosis and
      management of unfamiliar sacrococcygeal masses can be done.

PMID- 22654333
TI  - Large neurofibroma of trunk.
AB  - Neurofibroma is a benign tumor of cutaneous nerves. These are benign tumors which
      may have a varied presentations ranging from a cosmetic problem to a spinal tumor
      which may lead to neural complications. We here by present a case where the
      patient has become an appendage of the tumor and its the mass of the tumor that
      has handicapped the patient. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s12262-010-0129-x) contains supplementary
      material, which is available to authorized users.

PMID- 22654334
TI  - Double gall bladder-a rare entity.
AB  - Cholecystectomy is the most commonly performed operation in surgery. Variations
      inanatomical disposition are not infrequent. However variations in number of
      cystic ductand gall bladder is quiet rare. This poses a diagnostic and management
      problem withcomplications during surgery and missed gall bladder being reported
      in world literature. We here by report a case of double gall bladder with double
      cystic duct that was managed by laparoscopic surgery.

PMID- 22654335
TI  - Idiopathic neonatal colonic perforation- a case report.
AB  - Perforation of the transverse colon in neonate is a rare finding in clinical
      practice. We report a case of Idiopathic neonatal colonic perforation in a twenty
      one days old, healthy, female neonate without any demonstrable cause. She
      presented with abdominal distention and constipation. Abdominal radiograph showed
      massive pneumoperitoneum. On exploration, transverse colonic perforation was
      found near splenic flexure area. The perforation was closed primarily. Other than
      inflammatory fibrin flakes the rest of the large intestine and small bowel
      appeared normal. Hirschsprung's diseases, necrotizing enterocolitis, small left
      colon syndrome, atresia, imperforate anus, cystic fibrosis are some causes of
      colonic perforation in neonates. However none of the clinical features or intra
      operative finding of the above conditions could be found in our case. At follow
      up, the baby showed normal weight gain without any symptoms.

PMID- 22654336
TI  - Heteropagus twins-a tale of two cases.
AB  - Heteropagus twinning is a rare occurrence. Parasitic and asymmetric conjoined
      twins are rarer anomalies of monochorionic monoamniotic twins; which consist of
      an incomplete twin attached to the fully developed body of the co-twin. We
      present here two such cases of Heteropagus twinning.

PMID- 22654337
TI  - A Rare Case of FAP in Kashmir Valley.
AB  - Familial adenomatous polyposis (FAP) is the commonest form of inherited form of
      CRC. It comprises of about 5% of all the colorectal cancers (CRCs). FAP patients
      have a family history of CRC that suggests a genetic contribution, common
      exposures among family members, or a combination of both. This case report gives
      a glimpse of the phenotypic manifestation of FAP and the underlying molecular
      mechanism which leads to FAP, in addition it also sheds a light on the management
      of FAP in early stages of life.

PMID- 22654338
TI  - Plexiform neurofibroma of the submandibular salivary gland: a rare tumour.
AB  - A 15 year old boy presented with swelling in the submandibular region. X ray of
      the part showed faint radio opaque shadow. A provisional diagnosis of
      sialadenitis with sialiolithiasis was made. Excised mass was reported
      histopathologically as plexiform neurofibroma of submandibular salivary gland.
      Plexiform neurofibroma of the salivary gland is a rare benign tumour, often
      present in the parotid gland. It is very rare in submandibular salivary gland. It
      is a slow growing, locally infiltrating tumour. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s12262-010-0174-5)
      contains supplementary material, which is available to authorized users.

PMID- 22654339
TI  - Wunderlich's Syndrome in a Tuberous Sclerosis Patient.
AB  - Spontaneous non-traumatic renal hemorrhage known as Wunderlich's syndrome is
      known to occur in renal angiomyolipoma and may be the first manifestation of the
      disease. Angiomyolipomas in tuberous sclerosis are usually bilateral and
      multicentric. A 25yr old female, a case of Tuberous sclerosis with bilateral
      renal angiomyolipomas presented with right loin pain of increasing severity. On
      evaluation she had acute abdomen with increasing abdominal distension.
      Investigations revealed large right perinephric hematoma with bilateral renal
      angiomyolipomas. Exploratory laparotomy and right nephrectomy was done.
      Spontaneous hemorrhage in renal angiomyolipoma in a case of tuberous sclerosis
      and management are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s12262-010-0231-0) contains supplementary
      material, which is available to authorized users.

PMID- 22654340
TI  - Laparoscopic resection of a gastric glomus tumor.
AB  - Surgeons are commonly asked to evaluate patients with subepithelial masses of the
      stomach. Glomus tumors are subepithelial mesenchymal tumors that are rarely
      included in the differential diagnosis when evaluating these patients. We present
      the case of 55-year old man with a gastric glomus tumor that was diagnosed
      preoperatively and removed by laparoscopic wedge resection. We review the
      preoperative evaluation and classic finding associated with this uncommon entity.

PMID- 22654341
TI  - Leiomyoma of testis -a case report.
AB  - Leiomyomas, benign tumors, can arise from any organ containing smooth muscle. In
      the genitourinary tract, the renal capsule is most commonly involved.
      Intrascrotal leiomyomas are infrequently seen. Testis-associated leiomyomas are
      extremely rare. We report here testis associated leiomyoma.

PMID- 22654342
TI  - A rare presentation of mass abdomen.
AB  - An elderly male who had undergone inguinal hernia surgery eight years back
      presented with an intra-abdominal mass. Clinically and radiologically it was
      diagnosed as mesenteric cyst. Laparotomy revealed a thick walled cyst embedded in
      the omentum, containing brownish necrotic material and few 'linen thread knots'.
      On the basis of the latter finding the mass was thought to be a walled off
      hematoma, a complication of previous hernia surgery. Such a complication of
      inguinal surgery has not been reported earlier.

PMID- 22654343
TI  - Omphalolith.
AB  - Omphalolith (Umbolith) is uncommon under normal circumstances. However in a
      deeply retracted umbilicus in an obese individual, accumulation of sebum and
      keratin may lead to the formation of a stone. This calculus may remain
      undiagnosed for many years until revealed by secondary infection or ulceration.We
      report an intersting case of omphalolith in an elderly woman.

PMID- 22654344
TI  - An unusual bump on the head: spontaneous superficial temporal artery aneurysm.
AB  - This case report describes a spontaneous superficial temporal artery aneurysm.
      Although characteristically post traumatic in nature, in the absence of trauma, a
      spontaneous superficial temporal artery aneursym can form part of the
      differential diagnosis when confronted with a pulsatile swelling over the temple.

PMID- 22654345
TI  - "Letter to the editor".

PMID- 22654347
TI  - A comparative analysis of the effect of various denture adhesives available in
      market on the retentive ability of the maxillary denture: an in vivo study.
AB  - "Every human being has a divine right to enjoy the health to its fullest." Oral
      and Dental health is not an exception to this dictum. The speciality of
      Prosthodontics has emerged as a science to provide replacement of missing
      dentition for its form and functions along with associated structures. Any
      successful complete denture treatment combines exemplary technique, effective
      patient rapport, patient education, and familiarity with all possible management
      options in order to provide maximum satisfaction to patient. There are some
      forcing situations where providing desirable (optimal) retention may be a
      problem. In such types of patients use of denture adhesives is recommended for
      enhancing the quality of retention. The use of denture adhesive provides comfort
      and additional confidence not only by increasing the adhesive and cohesive but
      also eliminating voids between the denture base and the basal seat. This study is
      undertaken to evaluate the enhancement of retentive quality of complete denture
      with the use of denture adhesives available in Indian markets for the use by
      denture wearers.

PMID- 22654346
TI  - An appraisal on increasing the occlusal vertical dimension in full occlusal
      rehabilitation and its outcome.
AB  - Increasing the occlusal vertical dimension for gaining sufficient restoration
      space in the management of severely worn dentition is being practiced. This
      contentious belief has lead to challenging thoughts regarding its effects on the
      Odonto-stomatognathic system. There are basic uncertainties and existing
      erroneous thoughts regarding the perception of increasing the occlusal vertical
      dimension. This manuscript will review the bite raising concepts and its outcome
      on the stomatognathic system.

PMID- 22654348
TI  - Shear bond strength of composite veneers and acrylic veneer bonded to ni-cr
      alloy: a laboratory study.
AB  - A growing number of composite materials are being used as an alternative for
      veneering cast restorations. The objective of this investigation was to evaluate
      and compare the shear bond strength of UDMA based composite, restorative
      composite, and heat cure acrylic when veneered to Ni-Cr alloy and to evaluate the
      type of bond failure. Three different veneering materials were used: heat cure
      acrylic, UDMA based composite and a restorative composite. 10 samples were
      fabricated, each with heat cure acrylic and restorative composite and 20 samples
      were fabricated with UDMA based composite; thus, the total number of samples
      amounted to 40. All the samples were subject to shear bond stress fracture tests
      and observed for the type of bond failure. The greatest mean shear bond strength
      was recorded in relation to the UDMA based composite material when thermal
      conducting paste was used during the curing (10.51 MPa). The mean bond strength
      values of UDMA based composite without thermal conducting paste (8.92 MPa), heat
      cured acrylic veneering material (4.24 MPa) and restorative composite material
      (5.03 MPa) were significantly different from each other (p > 0.05). Samples
      veneered with heat cure acrylic veneering material and restorative composite
      material showed adhesive failure. Samples prepared with UDMA based composite
      veneering composite showed cohesive or predominantly cohesive failure. UDMA based
      composite veneering material when used with heat protection paste exceeds the
      shear bond strength requirement as suggested by Matsumura et al. (>10 MPa). A
      statistically significant association between the test groups and the type of
      failure was observed.

PMID- 22654349
TI  - A Study on Prevalence of Dental Attrition and its Relation to Factors of Age,
      Gender and to the Signs of TMJ Dysfunction.
AB  - A study was planned to determine the severity of dental attrition in adults of
      both sexes in different age groups and its possible relationship to
      temporomandibular disorders. 500 subjects comprising of 260 females and 240 males
      in the age group of 18-55 years were clinically examined for bruxism, attrition,
      and signs of temporomandibular disorders. Tooth sensitivity, tooth or restoration
      fracture, scalloping of tongue, ridging of buccal mucosa, TMJ sounds, muscle
      tenderness, TMJ tenderness, referred pain, pain on mouth opening and limitation
      of mouth opening were recorded along with attrition score in a proforma. The
      basic data was then analysed to arrive at certain conclusions. A high prevalence
      of attrition (88.0%) with increase in age (P < 0.00) and was seen more in males
      as compared to females (P < 0.01). On comparing attrition with some of the signs
      of bruxism it was shown that tooth or restoration fracture and scalloping of
      tongue had no relation to the severity of attrition score. Whereas a significant
      relation was seen between attrition and tooth sensitivity (P < 0.00), and ridging
      of buccal mucosa (P < 0.05). Muscle tenderness (P < 0.00), pain on mouth opening
      (P < 0.05) and deviation of mandible on mouth opening (P < 0.00) had significant
      relation to attrition. Other signs of temporomandibular disorders such as joint
      tenderness, referred pain, joint sounds and limitation of mouth opening had no
      relation to attrition score. This study showed a limited association between the
      severity of attrition and TMJ dysfunction.

PMID- 22654350
TI  - An invitro analysis of elemental release and cytotoxicity of recast nickel
      chromium dental casting alloys.
AB  - Recasting of the casting alloys affects the composition and elemental release
      which may have cytotoxic effect different from the pure alloy in the surrounding
      tissues. An Invitro study was conducted to investigate the elemental release and
      their cytotoxic effects from commercially available Ni-Cr dental casting alloys,
      commonly used for fabricating fixed partial dentures. Three Ni-Cr alloys [Wiron
      99(A), Ceramet (B), and Hi Nickel CB (C)] were tested. Alloy specimens (disks 3 *
      5 mm) were casted and grouped as follows: Group I (A(1)/B(1)/C(1)): 100% pure
      alloy; Group II (A(2)/B(2)/C(2)): 50% new with 50% recast; and Group III
      (A(3)/B(3)/C(3)): 100% recast. Disks of each alloy type from each group were
      transferred to Dulbecco's modified eagle medium and left for 3 days at 37 degrees
      C in an atmosphere of 5% CO(2). Ni, Cr, Co, Cu and Mo elemental release from
      metal alloys into culture medium was investigated using Inductively Coupled
      Plasma Mass Spectrometry. Cytotoxicity was tested using mouse fibroblast cells
      and MTT Assay. Controls consisted of 6 wells containing cells with no alloy
      specimens. Data were analyzed by two-way analysis of variance followed by t-test.
      The total amount of elements released in parts per billion for various casting
      groups were Group I, A(1)-6.572, B(1)-6.732, C(1)-8.407; Group II, A(2)-22.046,
      B(2)-26.450, C(2)-29.189; Group III, A(3)-84.554, B(3)-88.359, C(3)-92.264. More
      amounts of elements were released in Hi Nickel CB than Ceramet and Wiron 99 in
      all the three test groups. Percentage of viable cells from MTT analysis were
      Group I, A(1)-62.342, B(1)-61.322 C(1)-60.593, Group II, A(2)-58.699, B(2)
      56.494, C(2)-52.688, Group III, A(3)-53.101, B(3)-52.195, C(3)-47.586. The viable
      cells present in the culture media were more in Wiron 99 than Ceramet and Hi
      Nickel CB. Elemental release increased with amount of recast alloy. Amongst the
      three alloys tested Hi Nickel CB had significantly higher elements released
      compared to Ceramet and Wiron 99 in 100% pure alloys, 50% recast and 100% recast
      alloys. Wiron 99 showed least element release in 100% pure alloy, 50% recast and
      100% recast specimens. 100% pure alloys of all three alloys are less cytotoxic,
      but their cytotoxicity is more on 50% and 100% re-casted alloys. Out of all three
      variations of casting Wiron 99 was least cytotoxic, followed by Ceramet and Hi
      Nickel CB. Recasting of alloys significantly increased the elements released and
      their cytotoxicity.

PMID- 22654351
TI  - Prosthetic rehabilitation of a patient with congenital Oro-nasal defect with an
      interim prosthesis: a case report.
AB  - Rehabilitation in patients with facial defects requires multidisciplinary
      approach involving a head and neck surgeon, a maxillofacial prosthodontist and a
      reconstructive surgeon. Here we discuss a case of mid-facial defect due to a
      congenital anomaly for which a sectional impression was made. A removable nasal
      prosthesis obturating oro-nasal defect along with an overlay partial maxillary
      denture for the correction of malocclusion was given to the patient till
      definitive reconstructive surgery was performed.

PMID- 22654352
TI  - Esthetic Management of Unilateral Cross Bite with Dento-vestibular Enhancement
      Prosthetic Appliance.
AB  - Unilateral crossbite is a commonly encountered condition in clinical practice.
      The most frequently employed treatment protocol to manage unilateral crossbite is
      orthodontic correction or orthognathic surgery or combination of both. When the
      clinical situation less favours both these modalities of management, a
      transitional prosthetic appliance--dentovestibular enhancement prosthetic
      appliance- can be effectively used to manage this condition.

PMID- 22654353
TI  - Crowns to create esthetics for mal-aligned central incisors: a case report.
AB  - This case report describes the smile design of crowded upper central anteriors in
      a female patient aged 25 years. The patient wanted the correction to be completed
      in a short period of time. A smile design schedule was drawn up involving root
      canal treatment of the central incisors and placing posts in both the teeth. All
      ceramic crowns were then fabricated to establish a very satisfactory and pleasing
      esthetics.

PMID- 22654354
TI  - Management of compromised ridges: a case report.
AB  - Complete denture therapy is an age old form of dental treatment. Ridge atrophy
      poses a clinical challenge towards the fabrication of a successful prosthesis.
      Extreme resorption of the maxillary and mandibular denture bearing areas results
      in sunken appearance of cheeks, unstable and non retentive dentures with
      associated pain and discomfort. This article describes the step by step
      rehabilitation procedure of a patient with atrophic ridges using a hollow
      maxillary complete denture with cheek plumpers attached to it and the recording
      of neutral zone to ensure a stable mandibular denture.

PMID- 22654355
TI  - A simplified chair-side technique with pre-fabricated directional rings in a case
      of divergent root retained overdenture.
AB  - Precision attachments have been largely ignored by most dental professionals for
      trivial reasons such as cost and reluctance of a practitioner to grasp the
      intricacies of its indications and applications. Precision attachments offer
      considerable advantages such as increased retention of a denture, preservation of
      teeth which are otherwise indicated for extraction, as a viable alternative to
      implant retained overdenture and the ability to obtain parallelism in divergent
      abutments. A prosthodontist who familiarizes himself with precision attachments
      will be in a position to suggest a better treatment options in retaining teeth
      which might otherwise be considered for extraction or immediate implant
      placement. In this clinical report, we have described an overdenture placed on a
      previously unfavourable abutment made favourable by placing directional rings to
      maintain parallelism thus facilitating easy insertion and removal of the
      prosthesis.

PMID- 22654356
TI  - Radicular stud attachment: an alternative to improved retention and esthetics.
AB  - With the increasing demand and popularity of dental implants, the use of
      removable partial dentures in replacing missing teeth has become less popular.
      One of the obvious limitations of RPD is the unsightly view of metal used for the
      retentive clasp and the difficulty in obtaining a good fit. This case report
      describes the use of a radicular stud attachment as an alternative method to
      obtain improved retention and esthetics.

PMID- 22654357
TI  - Prosthetic rehabilitation of a patient with a large mid face defect secondary to
      Basal cell carcinoma.
AB  - The art of maxillofacial prosthetics restores esthetics and function in patients
      with gross developmental or acquired defects of face and helps them to restore
      hope and ambition to lead a useful life. This valuable service provided by
      maxillofacial prosthodontist lifts the morale of the patient and thus aids in
      physical well being and quality of life. Diagnosis and treatment planning should
      include attention to each detail prior to rehabilitation process. This paper
      describes a clinical case of mid face defect due to basal cell carcinoma,
      rehabilitated with facial prosthesis and intraoral obturator.

PMID- 22654358
TI  - "Transport distraction osteogenesis for reconstruction of mandibular defects":
      our experience.
AB  - INTRODUCTION: Mandibular defects usually involve a combination of osseous and
      soft tissue deficiency and are among the most challenging problems in
      maxillofacial surgery, many options are available for mandibular reconstruction.
      One of the options discussed in literature recently being distraction
      osteogenesis. AIM AND OBJECTIVE: The aims and objectives of the study were to
      evaluate clinically the technique of distraction osteogenesis to reconstruct
      mandibular defects, using indigenous transport distractors, and to evaluate the
      efficacy of Indigenous transport distraction osteogenesis device. MATERIALS AND
      METHODS: A prospective, experimental study was designed to examine the use of
      transport distraction osteogenesis in the treatment of defects of the mandible.
      Four patients with defects of the mandible were subjected to distraction
      osteogenesis with indigenously manufactured distraction device. The regenerate
      was assessed clinically and radiographically. RESULTS: The results showed that
      the regenerate was clinically as hard as the adjacent unaffected mandible and
      radiologic evidence of bone regeneration was observed. The major advantage being
      regeneration of hard tissue and soft tissue components without the morbidity of
      donor site, so that functional rehabilitation of the patient is possible.
      CONCLUSION: Thus from our study it is shown that transport distraction
      osteogenesis using indigenous distractors is a reliable yet affordable option for
      reconstruction of mandibular defects.

PMID- 22654359
TI  - Evaluation of the perioperative use of 0.2% chlorhexidine gluconate for the
      prevention of alveolar osteitis after the extraction of impacted mandibular third
      molars: a clinical study.
AB  - PURPOSE: To clinically evaluate the perioperative use of 0.2% chlorhexidine
      gluconate for the prevention of alveolar osteitis, to assess the patient
      compliance to chlorhexidine and to prepare a comprehensive treatment plan to
      prevent alveolar osteitis after removal of an impacted third molar extraction.
      METHODS: A prospective study was done on 50 patients with bilaterally impacted
      lower third molars which were indicated for extraction. Extraction of impacted
      mandibular third molar on one side was done without using any mouthrinse. While
      extracting the third molar on the other side, patients were instructed to use
      chlorhexidine 0.2% mouth rinse for 8 days, 1 day preceding and 7 days following
      the surgery. They were instructed to use chlorhexidine 0.2% (Rexidine) mouth
      rinse for 30 s twice a day (before breakfast and after dinner) with 15 ml of the
      rinse with 1:1 dilution with clean water. All the patients were evaluated for
      pain, presence or absence of clot and condition of the alveolar bone for the
      diagnosis of dry socket. RESULTS: Incidence of dry sockets was 8%, when patients
      did not use 0.2% chlorhexidine gluconate perioperatively which is statistically
      significant. CONCLUSIONS: It appeared that the incidence of dry socket can be
      reduced significantly by using 0.2% chlorhexidne gluconate mouth rinse
      perioperatively (twice daily, 1 day before and 7 days after surgical extraction.

PMID- 22654360
TI  - Primary and secondary closure of the surgical wound after removal of impacted
      mandibular third molars.
AB  - AIM: The present study attempted the evaluation of Primary and secondary closure
      techniques after removal of impacted third molars in terms of healing, post
      operative pain and swelling. MATERIAL AND METHODS: 60 patients with impacted
      mandibular third molars were randomly divided into two groups of 30. Panoramic
      radiographs were taken to assess degree of eruption and to asses 3rd molar
      angulations to the long axis of 2nd molar. Teeth were extracted, and in Group 1
      the socket was closed by hermetically suturing the flap. In group II a 5-6 mm
      wedge of mucosa distal to the second molar was removed & the flap was
      repositioned. Interrupted sutures were given, so as to form a triangular opening
      distal to second molar measuring about 5 * 5 mm. Swelling and pain were evaluated
      for 7 days after surgery with the VAS scale. RESULTS: Study results showed that
      post operative Sequale were comparatively less in secondary closure group than
      the primary closure group. Pain showed statistically significant difference
      between two groups. Pain was less in secondary closure group from day 1 to day 7.
      Swelling & trismus was also significantly less in secondary closure group.
      Evaluation of the complications of these two techniques showed that delayed wound
      healing occurred in 66.6% of cases (20 cases out of 30) in secondary closure
      group where as dehiscence of suture line occurred in 33.33% of cases (10 out of
      30) in primary closure group. CONCLUSIONS: The results obtained in the present
      study enable us to conclude that, in cases of equal intra-operative difficulty,
      open healing of the surgical wound after removal of impacted third molars
      produces less post-operative swelling and pain than occurs with closed healing,
      by hermetically suturing the socket.

PMID- 22654361
TI  - Randomized double blind comparative study on the efficacy of Ibuprofen and
      aceclofenac in controlling post-operative sequelae after third molar surgery.
AB  - OBJECTIVE: To compare the efficacy of Ibuprofen and Aceclofenac in controlling
      pain, swelling and trismus following removal of impacted mandibular third molar
      teeth. To assess the patient's acceptability of these drugs. METHODS: The present
      double blind study was conducted on 60 adult patients for the surgical removal of
      impacted mandibular third molars. Drugs administered were Ibuprofen and
      Aceclofenac. Both the drugs were packed separately and coded with equal in
      number. After removal of impacted mandibular third molars, following parameters
      were studied: (1) Analgesic activity, (2) Maximum mouth opening, (3) Swelling.
      RESULTS: The scores were recorded preoperatively and on 1st, 3rd, 5th and 7th
      postoperative day. CONCLUSION: Ibuprofen has a marginal edge over Aceclofenac.
      Both the drugs were well accepted by the patients with no reported adverse
      effects.

PMID- 22654362
TI  - Bone regeneration in osseous defects using hydroxyapatite graft and the extent of
      ossification in osseous defects treated without grafts: a comparative evaluation.
AB  - OBJECTIVES: Objective of this study is to evaluate the new bone formation in bony
      defects following insertion of hydroxyapatite graft and to compare the efficacy
      and regenerative potential of this bone graft material. METHOD: The patients
      having osseous defects after surgery were selected. Preoperatively a brief
      history, examination, relevant blood investigation and radiographs were taken.
      Post operative observation period of 6 months was planned. Radiographic and bone
      scintigraphic (isotope study of bone activity) evaluation of bone specimens was
      completed in defined time. RESULTS: Radiographic evaluation indicated increased
      calcification surrounding the material, indicative of acceptance of the graft to
      the bone. Bone scintigraphic evaluation indicated area of increased bone
      metabolism and is evidenced as area of increased radiotracer uptake, namely 'hot
      spots' (active bone formation). CONCLUSION: It can be concluded that the
      hydroxyapatite graft met the clinical requirement of a bone substitute material
      which is biocompatible and non-allergic. The use of this material is advantageous
      over other bone grafts because of simplicity of application, cost effectiveness
      and easy availability. Due to its microstructure, complete resorption and neo
      bone formation took place during the course of this study.

PMID- 22654363
TI  - Self Tapping Screws v/s Erich Arch Bar for Inter Maxillary Fixation: A
      Comparative Clinical Study in the Treatment of Mandibular Fractures.
AB  - INTRODUCTION AND OBJECTIVE: Numerous methods have been described for achievement
      of Intermaxillary fixation in the treatment of fractures of facial skeleton.
      Conventional methods like Erich arch bars and eyelet wires are currently most
      common methods for achieving intermaxillary fixation (IMF), but they have their
      own disadvantages. Since 1989, IMF using intraoral self tapping IMF screws has
      been introduced for treatment of mandibular fractures. The aim of this work was
      to compare the efficacy, advantages, disadvantages indications and potential
      complications associated with Erich archbar v/s self tapping IMF screws in the
      management of mandibular fractures. METHODS: Twenty patients with mandibular
      fractures, reporting to Department of Oral and Maxillofacial Surgery, The Oxford
      Dental College, Bangalore were evaluated, to compare the efficacy of two
      techniques. The parameters considered were, time taken, perforations in the
      gloves, patient acceptance, oral hygiene, iatrogenic dental injuries, and needle
      stick injuries during IMF with Erich arch Bar and self tapping IMF screws.
      RESULTS: The mean time taken for IMF was 8.52 +/- 2.7 min with screws as compared
      to 100 min with Erich arch bars. Mean number of perforations were significantly
      more in Group II. Oral hygiene status was good in 90% and fair in 10% of Group I
      and 100% fair in Group II patients. CONCLUSION: Use of self tapping IMF screws
      for intermaxillary fixation is a valid alternative to conventional Erich arch
      bars in the treatment of mandibular fractures. Iatrogenic injury to dental roots
      is the most important problem to this procedure, which can be minimized by
      careful radiographic evaluation and treatment planning.

PMID- 22654364
TI  - Oral cancer: risk factors and molecular pathogenesis.
AB  - INTRODUCTION: Oral cancer is one of the most common cancers and it constitutes a
      major health problem particularly in developing countries. It is one of the
      leading causes of death. Tobacco and alcohol consumption appears to be the major
      determinants of oral cancer. MATERIALS AND METHODS: The literature search was
      carried out in NCBI Pubmed database using keywords "oral cancer", "risk factor",
      "epidemiology" and "patho*". Some basic information was also obtained from
      textbook and medical university websites. RESULTS: Several risk factors have been
      well characterized to be associated with oral cancer with substantial evidences.
      The development of oral cancer is a multistep process involving the accumulation
      of genetic and epigenetic alterations in key regulatory genes. Experimental
      pathological studies of oral cancer in animal models and direct molecular genetic
      analysis of oral cancer subjects in recent times have revealed a substantial
      amount of knowledge on specific gene alterations or other genetic mechanisms
      involved in initiation and subsequent progression. CONCLUSION: Considering known
      risk factors, oral cancer appears to be to a certain extent, a preventable
      disease. Recent development of molecular picture of pathoprogression and
      molecular genetic tools opens the avenue for easier diagnosis, better
      prognostication and efficient therapeutic management.

PMID- 22654365
TI  - Management of zygomatic complex fractures in a tertiary hospital: a retrospective
      study.
AB  - AIM: This retrospective study was done to analyse the management of zygomatic
      complex fractures necessitating surgical intervention in a tertiary care hospital
      in a 8 year period in terms of incidence, cause, pattern and treatment. MATERIALS
      AND METHODS: Two hundred and thirteen cases of zygomatic complex fractures
      treated during this period were analysed. RESULTS: One hundred and eighty three
      cases of zygomatic complex fractures were treated by a two point fixation while
      additional fixation was used in 25 cases and single point fixation in five cases.
      The main etiology in zygomatic complex fractures was Road traffic accidents (RTA)
      (83.56 %-178 cases) followed by sport injuries (10 cases-4.65%), accidental falls
      (19 cases-8.9%) and domestic violence (2.81%-6 cases). The average age at the
      time of injury was 34.36 years with the age range being 7 years to 75 years. The
      highest incidence of fractures was seen in the third decade of life (102 cases)
      (47.88 %) followed by the second decade (44 cases) (20.65%), 41 cases (19.24 %)
      in the 4th decade, 8 cases each (3.75%) in the 5th and 6th decades, six cases
      (2.81%) in the 7th decade and four cases (1.87%) in the 8th decade. CONCLUSION:
      The protocol of two point fixation was found to be adequate in most cases of
      zygomatic complex fractures in terms of stability and restoration of contour and
      function.

PMID- 22654366
TI  - Pterygoid disjunction for internal derangement of temporomandibular joint.
AB  - AIM: The aim of this study was to clinically evaluate the outcomes of pterygoid
      disjunction (PD) carried out as the primary treatment modality for reducing disc
      displacement type of internal derangement (ID) of temporomandibular joint (TMJ)
      refractory to conservative management and arthrocentesis. PATIENTS AND METHOD: 59
      PD were carried out in 33 patients. In 26 cases procedure was done bilaterally
      and in 7 cases unilaterally as per the presentation from 2008 to 2010. Three
      patients were lost to follow up. Using the Helkimo Anamnestic and Clinical
      Dysfunction Indices cases were evaluated pre and postoperatively after 1 year.
      RESULTS: All 30 cases showed improvement. After 1 year follow up 6 cases were in
      Dio and 22 cases were in DiI and 2 cases were in DiII of clinical dysfunction
      index. From which we can co-relate that post surgically all the patients were
      benefited by this procedure. CONCLUSION: PD as a primary surgical option
      significantly reduces pain and improves function in the refractory cases of
      reducing disc displacement type of ID of TMJ.

PMID- 22654367
TI  - Verrucous carcinoma of the oral cavity: a histopathologic study of 10 Japanese
      cases.
AB  - OBJECTIVE: To reports ten Japanese surgical cases of verrucous carcinoma (VC) of
      the oral cavity. STUDY DESIGN: The author reviewed histopathology of 10 cases of
      oral VC. RESULTS: Ten cases of oral VC were found in our pathology department in
      the last 10 years. During the 10 years, a total of 187 cases of oral malignancy
      were recognized. Therefore, the frequency of VC was 5.3% of all oral
      malignancies. The patients consisted of six women and four men. The age ranged
      from 52 to 84 years with a median of 68 years. The locations of VC were buccal
      mucosa in two cases, gingiva in three cases, hard palate in one case, tongue in
      three cases, and soft palate in one case. The presenting symptoms were oral
      discomfort in two cases and tumors in eight cases. All cases underwent surgical
      resection. Frozen sections were performed in three cases for margin check.
      Grossly, all cases showed verrucous lesions. The size ranged from 0.8 to 3.2 cm
      with a median of 1.3 cm. Histologically, tumor cells proliferated with verrucous
      or papillary features. The tumor cells had acidophilic, ample cytoplasm, and
      nuclear atypia was minimal. Individual keratinization, koilocytosis, basal cell
      mild atypia, and squamous pearl formation were recognized in all cases. Three
      cases showed microinvasion. One case had focal ordinary squamous cell carcinoma
      within the VC. Epithelial dysplasia in the mucosa was recognized in the vicinity
      of VC in two cases. One case showed multiple tumors of VC; the number was five.
      Lymphocytic infiltration in the dermis was recognized in seven cases.
      Immunohistochemically, p53 protein was positive in all the ten cases. Its
      location was accentuated near the basal cells and microinvasive parts. Ki-67
      positive cells were also seen mainly in the basal cells and in the microinvasive
      areas, and the KI-67 labeling index ranged from 12 to 21%. Two patients recurred,
      and additional operations were performed. None show metastatic lesions. One
      patient died of other disease, and nine patients are now alive without tumors.
      CONCLUSION: Clinicopathologic features of ten cases of oral VC were described.

PMID- 22654368
TI  - Treatment of lymphangioma of the face with intralesional bleomycin: case
      discussion and literature review.
AB  - Surgical treatment of lymphangioma of the face is a difficult task to achieve due
      to close vicinity of the lesion to the facial nerve and possibility of scar
      tissue formation. Inefficient surgical removals generally will give rise to high
      recurrence rates because of infiltrative and diffuse extension of the lesion.
      However, complete cure has been described by non-surgical methods. A 5-year-old
      girl with extensive lymphangioma of the left cervicofacial area was treated with
      intralesional bleomycin injection under ultrasonographic guidance. Case
      discussion and related literature review was presented.

PMID- 22654369
TI  - Juvenile Psammomatoid Ossifying Fibroma (JPOF) of Maxilla-a Rare Entity.
AB  - Juvenile Ossifying Fibroma (JOF) is an uncommon fibro-osseous lesion affecting
      the facial bones. Although a benign entity, JOF is known to be locally aggressive
      and has a high tendency to recur. Two distinctive microscopic patterns have been
      described; a trabecular variant and a Psammomatoid variant. The latter variant is
      predominantly a craniofacial lesion and occurs rarely in the jaws. We report a
      rare case of Psammomatoid Juvenile ossifying fibroma that occurred in maxilla of
      a 20 year old female patient.

PMID- 22654370
TI  - Primary giant cell rich osteosarcoma of maxilla: an unusual case report.
AB  - Giant cell rich osteosarcomas, histological variant of conventional osteosarcomas
      account for 3% of all cases of osteosarcomas and most of them are arise from the
      appendicular skeleton. Giant cell rich osteosarcomas have been rarely reported in
      the head and neck region. This is the first case report of giant cell rich
      variant of osteosarcoma in the maxilla. It is important to recognize this
      variant, as its prognosis is worse as compared to conventional osteosarcomas of
      the head and neck region. We here present a case of giant cell rich variant of
      osteosarcoma of the maxilla and along with its characteristic radiological and
      histopathological picture.

PMID- 22654371
TI  - Metastatic carcinoma of gingiva mimicking pyogenic granuloma.
AB  - A case of metastasis of lung carcinoma to mandibular gingiva in 46 year old man
      has been presented here. The patient suffered discomfort due to growth in the
      lower left molar region with occasional hemorrhage and increased mobility of his
      lower left molars. After extraction of the teeth curettage was performed and
      histopathological examination revealed similar findings to those found in the
      lung tumor. This case report emphasizes the need to recognize that the gingival
      masses similar to benign or inflammatory lesions may represent an initial sign of
      underlying distant malignant tumors.

PMID- 22654372
TI  - Cholesterol granuloma of the orbit. Report of cases and analysis of controversial
      treatment.
AB  - Cholesterol granuloma of the orbit is a rare entity originated from a foreign
      body reaction against cholesterol crystal. Its pathogenesis still remains
      unclear, while controversy is still present concerning its management. In the
      present report, two new cases of cholesterol granuloma of the orbit are presented
      and the authors focus on treatment considerations.

PMID- 22654373
TI  - Hemimasticatory spasm: a case report with a new management strategy.
AB  - Hemimasticatory spasm is a rare neuromuscular disorder where the patient
      experiences involuntary, painful spasm of muscles of mastication. Only 15 cases
      have been reported in literature. We present a case which was treated
      unconventionally with satisfactory outcome.

PMID- 22654374
TI  - Destombes-rosai dorfman disease: a rare case report.
AB  - Destombes Rosai Dorfman disease and sinus histocytosis with massive
      lymphadenopathy is a rare benign idiopathic proliferative disease of phagocytic
      histiocytes. Approximately 80% of patient present with painless massive cervical
      lymphadenopathy. It rarely involves other sites for example CNS, eyes, upper
      respiratory tract and skin. A case of Destombes Rosai Dorfman disease is reported
      with history of gradual protrusion of left eye since many years. The histological
      features were consistent with the diagnosis.

PMID- 22654375
TI  - Lag screw fixation of fracture of the anterior mandible: a new minimal access
      technique.
AB  - OBJECTIVE: Purpose of this study to introduce a new minimal access technique for
      management of anterior mandible fracture with several advantages over
      conventional methods. METHOD: Four cases of undisplaced anterior mandibular
      fracture were selected. Tension band was achieved either by arch bar fixation to
      mandible or placement of interdental wire followed by intermaxillary fixation.
      With a 1 cm vertical incision was placed adjacent to fractured line. Fractured
      segment was immobilized with lag screw with minimal stripping. All patients were
      followed for 6 months. RESULTS: All four cases shown good stable segment after 6
      months of post operative follow up. OPG revealed well placed lag screw and there
      were no surgical complications, for example parasthesia, scarring and odema.
      CONCLUSION: Fixation of anterior mandible fracture using this technique can
      achieve good stability and appropriate compression. The technique is simple and
      easily performed, reducing the surgical time, reduce the chances of infection due
      to less exposure and promote the healing process by producing stress in the
      fracture lines.

PMID- 22654376
TI  - Letter to the editor.

PMID- 22654377
TI  - Preface, MSM 2012.

PMID- 22654378
TI  - Psychopharmacology of schizophrenia: The Future Looks Bleak.
AB  - INTRODUCTION: More than half a century after the introduction of effective
      pharmacotherapy for the illness, in most patients schizophrenia remains a
      chronic, relapsing condition with poor long-term outcomes. METHODS: We examine
      the pharmacological treatment of schizophrenia from different perspectives to
      understand why there have not been significant advances, and to consider what the
      future might hold in store. RESULTS: We argue that the treatment of schizophrenia
      addresses the phenotype and not the cause; that the causes may not be treatable
      even if identifiable; that secondary prevention approaches involving treating the
      phenotype before full-fledged illness develops have, so far, not yielded
      promising results; and that shifting the focus of treatment from dopamine to
      other neurotransmitter systems is merely a tertiary prevention approach which
      will not reverse the extensive structural and functional pathology of
      schizophrenia. CONCLUSIONS: We believe that, given the current state of our
      knowledge of the illness, the future of the pharmacotherapy of schizophrenia
      looks bleak.

PMID- 22654379
TI  - The future of schizophrenia pharmacotherapeutics: not so bleak.
AB  - Chlorpromazine efficacy in schizophrenia was observed 60 years ago. Advances in
      pharmacotherapy of this disorder have been modest with effectiveness still
      limited to the psychosis psychopathology and mechanism still dependent on
      dopamine antagonism. While a look backward may generate pessimism, future
      discovery may be far more robust. The near future will see significant changes in
      paradigms applied in discovery. Rather than viewing schizophrenia as a disease
      entity represented by psychosis, the construct will be deconstructed into
      component psychopathology domains. Each domain will represent a clinical target
      for aetiologic and therapeutic discovery. Research on pathophysiology will shift
      to the neural circuit level in relation to specific behavioural constructs.
      Progress at the molecular, genetic, cellular and network levels will be more
      robust. The behavioural paradigm will map on to the deconstructed clinical
      paradigm and in the process discovery will cut across current classification
      boundaries.

PMID- 22654380
TI  - Treatment-resistant Schizophrenia: Evidence-based Strategies.
AB  - Treatment-resistant symptoms complicate the clinical course of schizophrenia, and
      a large proportion of patients do not reach functional recovery. In consequence,
      polypharmacy is frequently used in treatment-refractory cases, addressing
      psychotic positive, negative and cognitive symptoms, treatment-emergent side
      effects caused by antipsychotics and comorbid depressive or obsessive-compulsive
      symptoms. To a large extent, such strategies are not covered by pharmacological
      guidelines which strongly suggest antipsychotic monotherapy. Add-on strategies
      comprise combinations of several antipsychotic agents and augmentations with mood
      stabilizers; moreover, antidepressants and experimental substances are applied.
      Based on the accumulated evidence of clinical trials and meta-analyses,
      combinations of clozapine with certain second-generation antipsychotic agents and
      the augmentation of antipsychotics with antidepressants seem recommendable, while
      the augmentation with mood stabilizers cannot be considered superior to placebo.
      Forthcoming investigations will have to focus on innovative pharmacological
      agents, the clinical spectrum of cognitive deficits and the implementation of
      cognitive behavioral therapy.

PMID- 22654381
TI  - Suicide and antidepressants: what current evidence indicates.
AB  - The documented efficacy and long-term benefit of antidepressants in patients with
      recurrent forms of severe anxiety or depressive disorders support their use in
      those individuals with these disorders, who experience suicidal thoughts or
      behavior. In general, it is assumed that antidepressants are beneficial for all
      symptoms of depression, including suicidality. However, some evidence suggests
      that Selective Serotonin Reuptake Inhibitors [SSRIs] may cause worsening of
      suicidal ideas in vulnerable patients. Systematic reviews and pooled analysis of
      experimental, observational, and epidemiological studies have investigated the
      use of SSRIs and their association with suicidality. Taking account of the
      methodological limitations of these studies, the current evidence fails to
      provide a clear relationship between their use and risk of suicidality in adults.
      However, in children and adolescents, there appears to be a bit of increased risk
      of suicidal ideations and attempts, but not of completed suicides. This risk can
      be anticipated and managed clinically. Clinicians are, therefore, advised to
      maintain a close follow-up during the initial treatment periods and remain
      vigilant of this risk. This advisory, however, should not deter clinicians from
      the use of effective dosages of antidepressants for a sufficient period of time,
      in every age group of patients, when clinically needed, and if found suitable
      otherwise.

PMID- 22654383
TI  - Stigma of Mental Illness-1: Clinical reflections.
AB  - Although the quality and effectiveness of mental health treatments and services
      have improved greatly over the past 50 years, therapeutic revolutions in
      psychiatry have not yet been able to reduce stigma. Stigma is a risk factor
      leading to negative mental health outcomes. It is responsible for treatment
      seeking delays and reduces the likelihood that a mentally ill patient will
      receive adequate care. It is evident that delay due to stigma can have
      devastating consequences. This review will discuss the causes and consequences of
      stigma related to mental illness.

PMID- 22654384
TI  - Stigma of Mental Illness-2: Non-compliance and Intervention.
AB  - The consequences of stigma are preventable. We argue that individual attention
      should be provided to patients when dealing with stigma. Also, in order to deal
      with the impact of stigma on an individual basis, it needs to be assessed during
      routine clinical examinations, quantified and followed up to observe whether or
      not treatment can reduce its impact. A patient-centric anti-stigma programme that
      delivers the above is urgently needed. To this end, this review explores the
      experiences, treatment barriers and consequences due to stigma. We also offer
      putative solutions to this problem.

PMID- 22654385
TI  - The Foetal 'Mind' as a Reflection of its Inner Self: Evidence from Colour Doppler
      Ultrasound of Foetal MCA.
AB  - The unborn healthy foetus is looked upon as a blessing by one and all. A plethora
      of thoughts arise in the brains of expectant parents. But what goes on in the
      brain of the yet unborn still remains a mystery. 'Foetal mind' is a reflection of
      functions of its organs of sense, an instrument of knowledge that may even be
      reduced to machine to demonstrate the effect of sense organs and brain contact.
      Testimony to this fact are the various waveform patterns obtained non-invasively
      from the foetal Middle Cerebral Artery (MCA) by using Colour Doppler Ultrasound.
      Our study, conducted for evaluating the foetal MCA in a rural obstetric
      population in Maharashtra, India, explains how the MCA - a major artery supplying
      foetal brain, can give abundant information about foetal heart and foetal stress.
      When only the foetal heart is stressed by the presence of arrhythmias or ectopic
      beats, these changes are manifest in the foetal MCA velocity waveform pattern as
      seen on Colour Doppler study. When the entire foetus is under stress, as in cases
      of intra uterine growth retardation (IUGR), changes again manifest in the foetal
      MCA velocity waveform pattern and are designated as the foetal Brain Sparing
      Effect. Thus scientific evaluation of foetal MCA waveform can objectively
      demonstrate that the overtly non-communicating foetal brain indeed remains an
      internal organ of sense and a vital instrument of knowledge to clarify the
      various effects of sense organs and brain contact. Although the brain parenchyma
      or cerebral metabolism has not been studied here, cerebral vessels serve as a
      window to cerebral metabolism, as auto regulatory function of brain leads to
      changes in haemodynamics of cerebral vessels. Also, like other vessels, MCA
      mirrors foetal distress and IUGR; but unlike other vessels, e.g. the umbilical or
      uterine artery, which show these changes in the form of reduction or even
      reversal of diastolic flow, MCA shows an increase in diastolic component due to
      brain sparing effect. The unique connection between physical changes in the
      foetal heart, brain and mental operations are thus critically clarified to some
      extent, and this helps untangle and comprehend the lattice of mental operations.
      Although this preliminary study has its limitations, it still carries forward the
      present corpus of knowledge on the strength of its evidential and critical
      enquiry and helps unravel the concept of foetal consciousness.

PMID- 22654382
TI  - Drug therapy of attention deficit hyperactivity disorder: current trends.
AB  - Attention deficit hyperactivity disorder is a developmental disorder with an age
      onset prior to 7 years. Children with ADHD have significantly lower ability to
      focus and sustain attention and also score higher on impulsivity and
      hyperactivity. Stimulants, such as methylphenidate, have remained the mainstay of
      ADHD treatment for decades with evidence supporting their use. However, recent
      years have seen emergence of newer drugs and drug delivery systems, like osmotic
      release oral systems and transdermal patches, to mention a few. The use of
      nonstimulant drugs like atomoxetine and various other drugs, such as alpha
      agonists, and a few antidepressants, being used in an off-label manner, have
      added to the pharmacotherapy of ADHD. This review discusses current trends in
      drug therapy of ADHD and highlights the promise pharmacogenomics may hold in the
      future.

PMID- 22654386
TI  - Science of the mind.
AB  - The popular concept and practice of science as an exclusively objective exercise
      ignores the study of rich and unavoidable subjective phenomena relating to mind.
      This article proposes that as a process of generating knowledge from perceptual
      experiences, science-skill is innate to man, which demands precision and
      effective management of bias, and relies on faith for communication. It manifests
      in man along two dimensions, one of precision and the other of need and interest.
      Two more dimensions influence its practice and communicability. This
      dimensionality accommodates scientific study of diverse human experiences,
      including religion and spirituality. Evolution of scientific study of mind
      requires complementing the existing objective techniques with development of
      techniques for investigating subjective and intuitive experiences. It would also
      benefit by borrowing concepts and methodologies from ancient Indian philosophies
      and spiritual practices. Swami Vivekananda's observations are presented in this
      connection.

PMID- 22654387
TI  - Medicalization: current concept and future directions in a bionic society.
AB  - The article illustrates the main features of the concept of medicalization,
      starting from its theoretical roots. Although it is the process of extending the
      medical gaze on human conditions, it appears that medicalization cannot be
      strictly connected to medical imperialism anymore. Other "engines" of
      medicalization are influential: consumers, biotechnology and managed care. The
      growth of research and theoretical reflections on medicalization has led to the
      proposal of other parallel concepts like pharmaceuticalization, genetization and
      biomedicalization. These new theoretical tools could be useful in the analysis of
      human enhancement. Human enhancement can be considered as the use of biomedical
      technology to improve performance on a human being who is not in need of a cure:
      a practice that is increasingly spreading in what might be defined as a "bionic
      society".

PMID- 22654388
TI  - Democracy, Human Rights and Women's Health.
AB  - Significant improvements in human rights and democracy have been made since the
      adoption of the Universal Declaration of Human Rights by the United Nations in
      1948. Yet, human rights, especially women's rights, are still being violated in
      many parts of the developing world. The adverse effects of such violations on
      women's and children's health are well known, but they are rarely measured. This
      study uses cross-national data from over 145 countries to estimate the impact of
      democracy and respect for human rights on various measures of women's health
      while controlling for confounding socio-economic factors such as income,
      education, fertility and healthcare. It finds that democracy and regards for
      human rights contribute positively to women's health outcomes, as do socio
      economic variables.

PMID- 22654390
TI  - On being the Editor of the Medical Journal of Australia: Living dangerously.
AB  - Editorial independence is crucial for the viability of a journal and editors have
      many masters - the public, the readers, the authors and the owners. Negotiating
      the resultant minefield requires a purposeful and independent stance. This is
      particularly so in instances of a relatively modern phenomenon: concerted
      attempts by clinical groups to influence, or even abort, publication of articles,
      which may threaten their practice. Moreover, modern social media facilitates this
      manipulation.

PMID- 22654389
TI  - Of money and trust in medical care redux.
AB  - Should we be concerned about financial conflicts of interest (COI) between
      doctors and the pharmaceutical industry? Some people will say no as there are
      clearly doctors who celebrate the relationship. Others say that it does not
      matter to patients, but the evidence says otherwise. Financial COI is different
      from other types of conflicts because it is voluntary and can be refused.
      Finally, it is not just the large gifts that are a problem, the small ones also
      create a "gift relationship." Drug companies know about this and spend billions
      on promotion with good effect from their point of view. Companies also woo
      doctors who honestly hold pro-industry points of view to speak on behalf of the
      companies. There are still multiple examples of financial COI, and although there
      are isolated examples of improvement, this is still an area of deep concern.

PMID- 22654392
TI  - Proposal about scientific names giving.

PMID- 22654391
TI  - Criminals in the Citadel and Deceit all along the Watchtower: Irresponsibility,
      Fraud, and Complicity in the Search for Scientific Truth.
AB  - Scientific research aims to use reliable methods to produce generalizable new
      knowledge in order to understand the human condition and maximize human
      potential. The sanctity accorded to scientific research has been violated by
      numerous instances of research fraud, as well as deceptive and conflicted
      research that have seriously harmed people, subverted the evidence-base, wasted
      valuable resources, and undermined public trust. This deception by individuals
      has been fostered by the unrealistic expectations of society; facilitated by the
      complicity of institutions and organisations; and sanctioned by the inaction of
      supposed gate-keepers. Re-defining misconduct as occurring on a continuum from
      irresponsible to fraudulent is the first step in confronting this inconvenient
      truth. Implementing and evaluating multiple strategies targeting systems and
      individuals that promote the responsible conduct of research, rather than merely
      exposing serious instances of misconduct by individuals, is urgently required to
      restore faith in the aspirations, integrity, and results of scientific research.

PMID- 22654393
TI  - Referencing modification in Mens Sana Monographs from 2012.

PMID- 22654394
TI  - A Slice of a Postgraduate Medical Resident's Life.

PMID- 22654395
TI  - Phlegmatic.

PMID- 22654397
TI  - Happy new year!

PMID- 22654396
TI  - And Bombay became a Village.

PMID- 22654398
TI  - Historical review of medicinal plants' usage.
AB  - Healing with medicinal plants is as old as mankind itself. The connection between
      man and his search for drugs in nature dates from the far past, of which there is
      ample evidence from various sources: written documents, preserved monuments, and
      even original plant medicines. Awareness of medicinal plants usage is a result of
      the many years of struggles against illnesses due to which man learned to pursue
      drugs in barks, seeds, fruit bodies, and other parts of the plants. Contemporary
      science has acknowledged their active action, and it has included in modern
      pharmacotherapy a range of drugs of plant origin, known by ancient civilizations
      and used throughout the millennia. The knowledge of the development of ideas
      related to the usage of medicinal plants as well as the evolution of awareness
      has increased the ability of pharmacists and physicians to respond to the
      challenges that have emerged with the spreading of professional services in
      facilitation of man's life.

PMID- 22654399
TI  - Chronopharmacognosy.
AB  - This study aims to review the concept of biological rhythms in medicinal plants.
      Dictionariesgenerally define pharmacognosy as the subject of the study of crude
      drugs of plant and animal origin. The name is derived from the Greek words
      pharmakon (drug) and gnosis (knowledge). Today pharmacognosy is also defined as
      the study of physical, chemical, biochemical and biological properties of drugs,
      drug substances, or potential drugs or drug substances of natural origin, as well
      as the search for new drugs from natural sources. Also, another important
      phenomenon to be taken care of in the production of therapeutic compounds in
      medicinal plants is the use of circardian clock. The circardian clock is studied
      by chronobiology, which can be defined as a field of science that examines
      periodic (cyclic) phenomena in living organisms and their adaptation to solar and
      lunar related rhythms. Thus, it is the scientific study of the effect of time on
      living systems and of biological rhythms. Also rhythmic oscillations in plants
      lead to the enormous production of particular compounds in plants at particular
      time, which may or may not produce any therapeutic effect in humans. Thus, the
      study of chronobiology and pharmacognosy can be put together as
      chronopharmacognosy.

PMID- 22654400
TI  - Fibrous drugs for curing various common health problems.
AB  - In the past 50 years, dietary fiber has become an increasingly significant area
      of nutritional focus, debate, and research. Advances in food production practices
      have resulted in more refined foods being available and consumed across the world
      and particularly in developed nations such as the US. While refined foods are
      typically more palatable to consumers, the content of dietary fiber is greatly
      reduced. Currently, many diseases are believed to be associated with a lack of
      dietary fiber intake and, furthermore, significant health benefits are thought
      possible via increased consumption of many dietary fibers. There is no well
      accepted definition for dietary fiber, but most of the references mention the
      inability of humans to fully digest fibers; most others say about fibers being
      made of various monomer units of variable length and some mention plant origin.
      There are many raw materials/ingredients that can increase the fiber content in
      foods, each with its own set of functional and sensory characteristics, including
      acacia gum, beta-glucan, cellulose, chitin/chitosan, corn bran, corn fiber,
      inulin, oat bran/oat fiber, pea fiber, pectin, polydextrose, psyllium, resistant
      starch, rice bran, soy fibers, wheat bran, and wheat fiber. All these fibers are
      unique in their functional capability for treatment of number of diseases.

PMID- 22654401
TI  - A brief review on anti diabetic plants: Global distribution, active ingredients,
      extraction techniques and acting mechanisms.
AB  - A study has been conducted with the aim to provide researchers with general
      information on anti diabetic extracts based on relevant research articles
      collected from 34 reliable medical journals. The study showed that Asian and
      African continents have 56% and 17% share of the worldwide distribution of
      therapeutic herbal plants, respectively. In Asia, India and China are the leading
      countries in herbal plants research, and there has been an increase in medicinal
      research on plants extract for diabetes treatment since 1995 in these regions.
      The information collected shows that plant leaves are about 20% more favorable
      for storing active ingredients, as compared to other parts of herbal plants. A
      brief review on the extraction techniques for the mentioned parts is also
      included. Furthermore, the acting mechanisms for the anti diabetic activity were
      described, and the related active ingredients were identified. The findings
      reveal that most of the anti diabetic research is focused on the alteration of
      glucose metabolism to prevent diabetes.

PMID- 22654402
TI  - The chemotherapeutic potential of Terminalia ferdinandiana: Phytochemistry and
      bioactivity.
AB  - Plants contain a myriad of natural compounds which exhibit important bioactive
      properties. These compounds may provide alternatives to current medications and
      afford a significant avenue for new drug discovery. Despite this, little
      information is available in the literature regarding native Australian plants and
      their potential for medicinal and industrial uses. Recent studies have reported
      Terminalia ferdinandiana to be an extremely good source of antioxidants. Indeed,
      T. ferdinandiana has been reported to have ascorbic acid levels per gram of fruit
      more than 900 times higher than blueberries. T. ferdinandiana also has high
      levels of a variety of other antioxidants, including phenolic compounds and
      anthocyanins. Antioxidants have been associated with the prevention of cancer,
      cardiovascular diseases, and neurological degenerative disorders. They are also
      linked with antidiabetic bioactivities and have been associated with the
      reduction of obesity. Antioxidants can directly scavenge free radicals,
      protecting cells against oxidative stress-related damage to proteins, lipids, and
      nucleic acids. Therefore, T. ferdinandiana has potential in the treatment of a
      variety of diseases and disorders and its potential bioactivities warrant further
      investigation.

PMID- 22654403
TI  - Functional herbal food ingredients used in type 2 diabetes mellitus.
AB  - From many reports it is clear that diabetes will be one of the major diseases in
      the coming years. As a result there is a rapidly increasing interest in searching
      new medicines, or even better searching prophylactic methods. Based on a large
      number of chemical and pharmacological research work, numerous bioactive
      compounds have been found in functional herbal food ingredients for diabetes. The
      present paper reviews functional herbal food ingredients with regards to their
      anti-diabetic active principles and pharmacological test results, which are
      commonly used in Asian culinary system and medical system and have demonstrated
      clinical or/and experimental anti-diabetic effectiveness. Our idea of reviewing
      this article is to give more attention to these functional food ingredients as
      targets medicinal foods in order to prevent or slow down the development of type
      2 diabetes mellitus.

PMID- 22654404
TI  - Borreria and Spermacoce species (Rubiaceae): A review of their ethnomedicinal
      properties, chemical constituents, and biological activities.
AB  - Borreira and Spermacoce are genera of Rubiaceae widespread in tropical and
      subtropical America, Africa, Asia, and Europe. Based on its fruits morphology
      they are considered by many authors to be distinct genera and most others,
      however, prefer to combine the two taxa under the generic name Spermacoce.
      Whereas the discussion is still unclear, in this work they were considered as
      synonyms. Some species of these genera play an important role in traditional
      medicine in Africa, Asia, Europe, and South America. Some of these uses include
      the treatment of malaria, diarrheal and other digestive problems, skin diseases,
      fever, hemorrhage, urinary and respiratory infections, headache, inflammation of
      eye, and gums. To date, more than 60 compounds have been reported from Borreria
      and Spermacoce species including alkaloids, iridoids, flavonoids, terpenoids, and
      other compounds. Studies have confirmed that extracts from Borreria and
      Spermacoce species as well as their isolated compounds possess diverse biological
      activities, including anti-inflammatory, antitumor, antimicrobial, larvicidal,
      antioxidant, gastrointestinal, anti-ulcer, and hepatoprotective, with alkaloids
      and iridoids as the major active principles. This paper briefly reviews the
      ethnomedicinal uses, phytochemistry, and biological activities of some isolated
      compounds and extracts of both genera.

PMID- 22654406
TI  - Trichosanthes dioica Roxb.: An overview.
AB  - Trichosanthes, a genus of family Cucurbitaceae, is an annual or perennial herb
      distributed in tropical Asia and Australia. Pointed gourd (Trichosanthes dioica
      Roxb.) is known by a common name of parwal and is cultivated mainly as a
      vegetable. Juice of leaves of T. dioica is used as tonic, febrifuge, in edema,
      alopecia, and in subacute cases of enlargement of liver. In Charaka Samhita,
      leaves and fruits find mention for treating alcoholism and jaundice. A lot of
      pharmacological work has been scientifically carried out on various parts of T.
      dioica, but some other traditionally important therapeutical uses are also
      remaining to proof till now scientifically. According to Ayurveda, leaves of the
      plant are used as antipyretic, diuretic, cardiotonic, laxative, antiulcer, etc.
      The various chemical constituents present in T. dioica are vitamin A, vitamin C,
      tannins, saponins, alkaloids, mixture of noval peptides, proteins tetra and
      pentacyclic triterpenes, etc.

PMID- 22654405
TI  - Trachyspermum ammi.
AB  - Trachyspermum ammi commonly known as 'Ajwain' is distributed throughout India and
      is mostly cultivated in Gujarat and Rajasthan. The fruit possesses stimulant,
      antispasmodic and carminative properties and is used traditionally as an
      important remedial agent for flatulence, atonic dyspepsia, diarrhea, abdominal
      tumors, abdominal pains, piles, and bronchial problems, lack of appetite,
      galactogogue, asthma and amenorrhoea. Medicinally, it has been proven to possess
      various pharmacological activities like antifungal, antioxidant, antimicrobial,
      antinociceptive, cytotoxic, hypolipidemic, antihypertensive, antispasmodic,
      broncho-dilating actions, antilithiasis, diuretic, abortifacient, antitussive,
      nematicidal, anthelmintic and antifilarial. Further, studies reveal the presence
      of various phytochemical constituents mainly carbohydrates, glycosides, saponins,
      phenolic compounds, volatile oil (thymol, gamma-terpinene, para-cymene, and alpha
      and beta-pinene), protein, fat, fiber and mineral matter containing calcium,
      phosphorous, iron and nicotinic acid. These studies reveal that T. ammi is a
      source of medicinally active compounds and have various pharmacological effects;
      hence, it is encouraging to find its new therapeutic uses.

PMID- 22654407
TI  - Ethnobotany, phytochemistry and pharmacology of Biophytum sensitivum DC.
AB  - Medicinal plants are widely being used by the traditional medical practitioners
      for curing various diseases in their day-to-day practice. Biophytum sensitivum DC
      (Oxalidaceae) is used as a traditional folk medicine in ailments such as
      inflammation, arthritis, wounds, tumors and burns, gonorrhea, stomach ache,
      asthma, cough, degenerative joint disease, urinary calculi, diabetes, snake bite,
      amenorrhea and dysmenorrhea. It is a small, flowering, annual herb with sensitive
      leaves. It grows throughout tropical Africa and Asia, especially in Philippines
      and the hotter parts of India and Nepal. Phytochemical studies have shown that
      the major pharmacologically active constituents are amentoflavone and a
      polysaccharide fraction, BP100 III. Recent pharmacological study shows that it
      has antioxidant, immunomodulatory, anticancer, anti-inflammatory,
      chemoprotective, antidiabetic and wound healing potential. This review attempts
      to describe the ethnobotany, pharmacognosy, traditional uses, chemical
      constituents, and various pharmacologic activities and other aspects of B.
      sensitivum.

PMID- 22654408
TI  - Chemical constituents and biological activities of the genus Subergorgia.
AB  - The genus Subergorgia (coelenterata, Gorgonacea, Subergorgiidae) is distributed
      in the Indo-pacific region. Previous investigations on the various species of the
      genus have revealed the presence of a number of new compounds including
      alkaloids, sesquiterpenes, diterpenes, and steroids. Certain biological
      activities particularly cytotoxic activity have been observed for the isolated
      constituents and compositions derived from the coral. This review covers the
      secondary metabolites reported from the genus Subergorgia and their biological
      properties.

PMID- 22654409
TI  - Reliability of the 8 Week Time Point for Single Assessment of Midcarpal Fusion by
      CT Scan.
AB  - High rates of nonunion have recently been reported for midcarpal fusions. Due to
      curvature and overlap of carpal interfaces, two dimensional films are not
      reliable in determining union of a midcarpal fusion. Computed tomography is the
      most reliable radiographic method of evaluating osseous union. Initiating motion
      as soon as fusion has occurred is a priority with the goal of maximizing final
      range. Cost control in healthcare makes obtaining serial scans unreasonable. The
      single optimal time point for a computed tomography scan to determine union of a
      midcarpal fusion remains to be determined. A prospective protocol selected 8
      weeks post operative as the point in time to obtain the single determining scan.
      Forty-six consecutive midcarpal fusions with scaphoidectomy were retrospectively
      analyzed for the reliability of this time point. All fusions had achieved union
      by 8 weeks and only this one scan was clinically necessary to advance the
      patients on to full range of motion without a splint at that time.

PMID- 22654410
TI  - Nerve transfers for traumatic brachial plexus injury: advantages and problems.
AB  - In recent years nerve transfers have been increasingly used to broaden
      reconstructive options for brachial plexus reconstruction. Nerve transfer is a
      procedure where an expendable nerve is connected to a more important nerve in
      order to reinnervate that nerve. This article outlines the experience of the
      Scottish National Brachial Plexus Injury Service as our use of nerve transfers
      has increased. Outcomes have improved for reconstruction of the paralysed
      shoulder using transfer of the accessory nerve to the suprascapular nerve. Medial
      pectoral to musculocutaneous nerve transfer has proved reliable for restoration
      of elbow flexion for patients with C5,6 and C5,6,7 injuries. Problems with nerve
      transfers include morbidity in the donor nerve territory, co-contraction, and pre
      existing injury to the donor nerve. There is a balance of risks in these
      procedures which should be weighed up in individual cases.

PMID- 22654411
TI  - The Influence of Non-union of the Ulnar Styloid on Pain, Wrist Function and
      Instability after Distal Radius Fracture.
AB  - The influence of non-union on the outcome of distal radius fractures is debated.
      We tested the null hypothesis that there is no difference in pain, wrist
      function, or instability between patients with union or non-union of an ulnar
      styloid base fracture after operative treatment of a fracture of the distal
      radius. Eighteen adults with an ulnar styloid base non-union were compared to 16
      patients with union of an ulnar styloid base fracture with a mean post-operative
      follow-up of 30 months. None of the patients had distal radioulnar joint
      instability, there were no significant differences in pain, complications, or
      function, and patients with nonunion had significantly greater grip strength.
      Ulnar styloid nonunion is not associated with pain, instability, or diminished
      function after fracture of the distal radius.

PMID- 22654412
TI  - Microvascular Anastomosis of Vessels Less Than 0.5 mm in Diameter: A
      Supermicrosurgery Training Model in Lagos, Nigeria.
AB  - The development of reconstructive microsurgery has now reached the
      supermicrosurgery stage. However the anastomosis of vessels under 0.5 mm is still
      out of the comfort zone of the many microsurgeons. To confirm the technical
      feasibility and the reliability of this technique We relate our own experience in
      this regard using the free superficial inferior epigastric flap of the rat as a
      model for supermicrosurgery training at the Microsurgery Laboratory of the Lagos
      University teaching hospital. 18 of the 20 free flaps transferred survived at 1
      week. Two flaps necrosed and two flaps dehisced. We believe based on our work
      that the average microsurgeon can become comfortable working with these vessels.

PMID- 22654413
TI  - A comparison of full and split thickness skin grafts in radial forearm donor
      sites.
AB  - To formally evaluate the functional and aesthetic outcomes between full versus
      split thickness skin graft coverage of radial forearm free flap donor sites. A
      retrospective chart review of 47 patients who underwent pedicled or free radial
      forearm free flap reconstruction from May 1997 to August 2004 was performed.
      Comparisons were made between patients who had donor site coverage with split
      thickness skin grafts (STSG) or full thickness skin grafts (FTSG). There was no
      statistically significant difference between the STSG and FTSG in the number of
      post-operative dressings, incidence of tendon exposure, time to healing at the
      skin graft donor site, and time to healing at the skin graft recipient site. The
      questionnaire data showed there was a trend toward higher scores with the radial
      forearm scar aesthetics and satisfaction in the FTSG group. Full thickness skin
      graft coverage of radial forearm free flap donor site is superior to split
      thickness skin graft coverage in terms of aesthetic outcome, and has no
      statistically significant difference in terms of tendon exposure, time to healing
      at the skin graft donor site, time to healing at the skin graft recipient site,
      or post operative pain.

PMID- 22654414
TI  - Digital metastasis presenting as infection.

PMID- 22654415
TI  - A rare poland syndrome deformity: humero-pectoral band.

PMID- 22654416
TI  - Aggressive Digital Papillary Adenocarcinoma in a Young Female-a Rare
      Presentation.
AB  - A 20 year old female presented with a recurrent soft tissue swelling over the
      medial aspect of proximal phalanx of left little finger. It had recurred one year
      after excision. There was no lymphadenopathy or bony involvement. Previous
      histopathology reports were not available. After excision histopathological
      diagnosis was aggressive digital papillary adenocarcinoma. Later Ray's amputation
      of little finger was planned. Aggressive digital papillary adenocarcinomas are
      rare sweat gland tumors which occur on hands, fingers, and toes. They have high
      local recurrence rate and may metastasize to lungs and lymph nodes.

PMID- 22654417
TI  - Combining an external fixator and an artificial nerve-guide for the treatment of
      a complex digital injury.
AB  - A complex digital injury, with tendon, nerve and bone losses, may pose the
      problem of which structure deserves the highest priority. Authors were able to
      treat tendon, nerve and bone lesions with the same level of priority thanks to
      the combined use of an external fixator and a nerve-guide.

PMID- 22654418
TI  - Simple bone cyst as a sequel of forearm plate osteosynthesis.
AB  - This report presents the long-term effect of plate osteosynthesis to repair a
      right forearm fracture in an 11-year old patient, who 6 years later requested
      removal of her plates because of the pain she was experiencing in the area. The
      17 year-old female had developed simple bone cysts around the implanted plates
      for her radius and ulnar fracture. Circulatory disturbances might have a role in
      the development of the simple bone cysts in this case.

PMID- 22654419
TI  - Lipoma of the middle finger hampering its movements.

PMID- 22654420
TI  - Hepatitis C virus infection and health-related quality of life.
AB  - Hepatitis C virus (HCV) hepatitis and other diseases related to HCV, such as
      cryoglobulinemia, lymphoma and renal failure, impair health-related quality of
      life (HRQoL). In addition, HCV per se might directly influence HRQoL via
      colonization of microglia in the brain or, indirectly, via the effect of systemic
      inflammatory cytokines which, in turn, can trigger brain interleukin production.
      The treatment of HCV-related disorders with interferon (IFN) has an effect on
      HRQoL. Initially, IFN causes a transient deterioration of HRQoL, due to the
      induction of depression and other side effects of treatment. Subsequently, the
      subjects who obtain a sustained virologic response experience an improvement in
      HRQoL. Only rarely does interferon treatment causes permanent detrimental effects
      on HRQoL, due to residual psychiatric or neurologic side effects. Liver
      transplantation is the only treatment for end-stage HCV-related liver disease.
      HRQoL generally improves massively a few months after transplantation, except in
      the case of serious complications of the transplant procedure. Furthermore, high
      levels of anxiety and neuroticism pre-transplant are associated with lower HRQoL
      one year after transplant. Additionally, six months after transplant, patients
      with HCV who experience virologic recurrence show significantly greater
      depression, anxiety, phobic anxiety, and paranoid ideation than anti-HCV-negative
      patients. In conclusion, optimal care for the overall well-being of patients with
      HCV infection requires adequate knowledge of their neurological and psychological
      status.

PMID- 22654421
TI  - Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat
      accumulates in the liver of a patient without a history of alcohol abuse.
      Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to
      liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic
      manifestation of metabolic syndrome and incidence has been increasing worldwide
      in line with the increased prevalence of obesity, type 2 diabetes, and
      hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in
      elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects
      of various agents. An ideal model of NAFLD/NASH should correctly reflect both
      hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of
      NAFLD/NASH are divided into genetic, dietary, and combination models. In this
      paper, we review commonly used animal models of NAFLD/NASH referring to their
      advantages and disadvantages.

PMID- 22654424
TI  - Anti-tumor effect of 5-aza-2'-deoxycytidine by inhibiting telomerase activity in
      hepatocellular carcinoma cells.
AB  - AIM: To investigate the effect of the demethylating reagent 5-aza-2'
      deoxycitidine (DAC) on telomerase activity in hepatocellular carcinoma (HCC) cell
      lines, SMMC-7721 and HepG2. METHODS: The related gene expression in cell lines
      was examined by real-time reverse transcription-polymerase chain reaction and
      Western blotting analysis. The telomerase activity was examined by telomeric
      repeat amplification protocol-enzyme-linked immunosorbent assay and DNA
      methylation was determined by methylation-specific polymerase chain reaction.
      RESULTS: The telomerase activity was significantly reduced in both cell lines
      treated with DAC, accompanied by downregulation of telomerase reverse
      transcriptase (hTERT). We also observed the effect of DAC on the methylation
      status of hTERT promoter and the expression of regulatory genes, such as c-myc,
      p15, p16, p21, E2F1, and WT1. The methylation status of hTERT promoter could be
      reversed in SMMC-7721 by DAC, but not in HepG2 cells. However, p16 expression
      could be reactivated by demethylation of its promoter, and c-Myc expression was
      repressed in both cell lines. Moreover, DAC could enhance the sensitivity to the
      chemotherapeutic agents, such as cisplatin, by induction of apoptosis of HCC
      cells. CONCLUSION: The DAC exerts its anti-tumor effects in HCC cells by
      inhibiting the telomerase activity.

PMID- 22654422
TI  - Gastric stimulation for weight loss.
AB  - The prevalence of obesity is growing to epidemic proportions, and there is
      clearly a need for minimally invasive therapies with few adverse effects that
      allow for sustained weight loss. Behavior and lifestyle therapy are safe
      treatments for obesity in the short term, but the durability of the weight loss
      is limited. Although promising obesity drugs are in development, the currently
      available drugs lack efficacy or have unacceptable side effects. Surgery leads to
      long-term weight loss, but it is associated with morbidity and mortality. Gastric
      electrical stimulation (GES) has received increasing attention as a potential
      tool for treating obesity and gastrointestinal dysmotility disorders. GES is a
      promising, minimally invasive, safe, and effective method for treating obesity.
      External gastric pacing is aimed at alteration of the motility of the
      gastrointestinal tract in a way that will alter absorption due to alteration of
      transit time. In addition, data from animal models and preliminary data from
      human trials suggest a role for the gut-brain axis in the mechanism of GES. This
      may involve alteration of secretion of hormones associated with hunger or
      satiety. Patient selection for gastric stimulation therapy seems to be an
      important determinant of the treatment's outcome. Here, we review the current
      status, potential mechanisms of action, and possible future applications of
      gastric stimulation for obesity.

PMID- 22654423
TI  - Matrix metalloproteinase-9 contributes to parenchymal hemorrhage and necrosis in
      the remnant liver after extended hepatectomy in mice.
AB  - AIM: To investigate the effect of matrix metalloproteinase-9 (MMP-9) on the
      remnant liver after massive hepatectomy in the mouse. METHODS: Age-matched,
      C57BL/6 wild-type (WT), MMP-9(-/-), and tissue inhibitors of metalloproteinases
      (TIMP)-1(-/-) mice were used. The mice received 80%-partial hepatectomy (PH).
      Samples were obtained at 6 h after 80%-PH, and we used histology,
      immunohistochemical staining, western blotting analysis and zymography to
      investigate the effect of PH on MMP-9. The role of MMP-9 after PH was
      investigated using a monoclonal antibody and MMP inhibitor. RESULTS: We examined
      the remnant liver 6 h after 80%-PH and found that MMP-9 deficiency attenuated the
      formation of hemorrhage and necrosis. There were significantly fewer and smaller
      hemorrhagic and necrotic lesions in MMP-9(-/-) remnant livers compared with WT
      and TIMP-1(-/-) livers (P < 0.01), with no difference between WT and TIMP-1(-/-)
      mice. Serum alanine aminotransaminase levels were significantly lower in MMP-9(-/
      ) mice compared with those in TIMP-1(-/-) mice (WT: 476 +/- 83 IU/L, MMP-9(-/-):
      392 +/- 30 IU/L, TIMP-1(-/-): 673 +/- 73 IU/L, P < 0.01). Western blotting and
      gelatin zymography demonstrated a lack of MMP-9 expression and activity in MMP-9(
      /-) mice, which was in contrast to WT and TIMP-1(-/-) mice. No change in MMP-2
      expression was observed in any of the study groups. Similar to MMP-9(-/-) mice,
      when WT mice were treated with MMP-9 monoclonal antibody or the synthetic
      inhibitor GM6001, hemorrhagic and necrotic lesions were significantly smaller and
      fewer than in control mice (P < 0.05). These results suggest that MMP-9 plays an
      important role in the development of parenchymal hemorrhage and necrosis in the
      small remnant liver. CONCLUSION: Successful MMP-9 inhibition attenuates the
      formation of hemorrhage and necrosis and might be a potential therapy to
      ameliorate liver injury after massive hepatectomy.

PMID- 22654425
TI  - Lactobacillus crispatus M206119 exacerbates murine DSS-colitis by interfering
      with inflammatory responses.
AB  - AIM: To investigate the role of Lactobacillus crispatus (L. crispatus) strain
      China Center for Type Culture Collection (CCTCC) M206119 in intestinal
      inflammation. METHODS: Forty 8-wk-old Balb/c mice (20 +/- 2 g) were divided into
      four groups of 10 mice each. Three groups that had received dextran sulfate
      sodium (DSS) were administered normal saline, sulfasalazine or CCTCC M206119
      strain, and the fourth group received none of these. We assessed the severity of
      colitis using a disease activity index, measured the colon length and weight,
      collected stools and mesenteric lymph nodes for bacterial microflora analysis.
      One centimeter of the proximal colon, middle colon and distal colon were
      collected and fixed in 10% buffered formalin, dehydrated in ethanol, and embedded
      in paraffin. Interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha
      expression was detected using reverse transcription polymerase chain reaction.
      Protective factors zonula occludens (ZO)-1 and beta-defensin 2 were detected by
      immunoblotting. The features of CCTCC M206119 strain were identified based on
      morphology, biochemical profile, and 16S RNA sequencing. RESULTS: DSS-colitis
      animals treated with CCTCC M206119 had markedly more severe disease, with greater
      weight loss, diarrhea, fecal bleeding, and shortened colon length. In addition,
      the CCTCC-M206119-treated group had comparatively higher histological scores and
      more neutrophil infiltration than the controls. Expression of protective factors
      ZO-1 and beta-defensin 2 was downregulated due to destruction of the mucosal
      barrier after CCTCC M206119 strain treatment. An in vitro assay demonstrated that
      CCTCC M206119 strain increased the nuclear translocation of nuclear factor-kappaB
      in epithelial cells. Intestinal proinflammatory or anti-inflammatory cytokine
      responses were evaluated. Proinflammatory colonic cytokine (IL-1beta, IL-6 and
      TNF-alpha) levels were clearly increased in CCTCC-M206119-treated animals,
      whereas anti-inflammatory colonic cytokine (IL-10) level was lowered compared
      with saline or 5-aminosalicylic-acid-treated DSS-colitis mice. Next, CCTCC
      M206119 strain was characterized as L. crispatus by microscopic morphology,
      biochemical tests and 16S rRNA gene level. CONCLUSION: Not all lactobacilli are
      beneficial for intestinal inflammation, and L. crispatus CCTCC M206119 strain is
      involved in exacerbation of intestinal inflammation in DSS-colitis mice.

PMID- 22654426
TI  - Endoscopic ultrasonography-guided fine needle aspiration: Relatively low
      sensitivity in the endosonographer population.
AB  - AIM: To assess the characteristics and quality of endoscopic ultrasonography
      guided fine needle aspiration (EUS-FNA) in a large panel of endosonographers.
      METHODS: A survey was conducted during the 13th annual live course of endoscopic
      ultrasonography (EUS) held in Amsterdam, Netherlands. A 2-page questionnaire was
      developed for the study. Content validity of the questionnaire was determined
      based on input by experts in the field and a review of the relevant literature.
      It contained 30 questions that pertained to demographics and the current practice
      for EUS-FNA of responders, including sampling technique, sample processing,
      cytopathological diagnosis and sensitivity of EUS-FNA for the diagnosis of solid
      mass lesions. One hundred and sixty-one endosonographers who attended the course
      were asked to answer the survey. This allowed assessing the current practice of
      EUS-FNA as well as the self-reported sensitivity of EUS-FNA for the diagnosis of
      solid mass lesions. We also examined which factors were associated with a self
      reported sensitivity of EUS-FNA for the diagnosis of solid mass lesions > 80%.
      RESULTS: Completed surveys were collected from 92 (57.1%) of 161 endosonographers
      who attended the conference. The endosonographers had been practicing endoscopy
      and EUS for 12.5 +/- 7.8 years and 4.8 +/- 4.1 years, respectively; one third of
      them worked in a hospital with an annual caseload > 100 EUS-FNA. Endoscopy
      practices were located in 29 countries, including 13 countries in Western Europe
      that totaled 75.3% of the responses. Only one third of endosonographers reported
      a sensitivity for the diagnosis of solid mass lesions > 80% (interquartile range
      of sensitivities, 25.0%-75.0%). Factors independently associated with a
      sensitivity > 80% were (1) > 7 needle passes for pancreatic lesions or rapid on
      site cytopathological evaluation (ROSE) (P < 0.0001), (2) a high annual hospital
      caseload (P = 0.024) and (3) routine isolation of microcores from EUS-FNA samples
      (P = 0.042). ROSE was routinely available to 27.9% of respondents. For lymph
      nodes and pancreatic masses, a maximum of three needle passes was performed by
      approximately two thirds of those who did not have ROSE. Microcores were
      routinely harvested from EUS-FNA samples by approximately one third (37.2%) of
      survey respondents. CONCLUSION: EUS-FNA sensitivity was considerably lower than
      reported in the literature. Low EUS-FNA sensitivity was associated with
      unavailability of ROSE, few needle passes, absence of microcore isolation and low
      hospital caseload.

PMID- 22654427
TI  - Clinical benefit of radiation therapy and metallic stenting for unresectable
      hilar cholangiocarcinoma.
AB  - AIM: To determine the efficacy of external beam radiotherapy (EBRT), with or
      without intraluminal brachytherapy (ILBT), in patients with non-resected locally
      advanced hilar cholangiocarcinoma. METHODS: We analyzed 64 patients with locally
      advanced hilar cholangiocarcinoma, including 25 who underwent resection (17
      curative and 8 non-curative), 28 treated with radiotherapy, and 11 who received
      best supportive care (BSC). The radiotherapy group received EBRT (50 Gy, 30
      fractions), with 11 receiving an additional 24 Gy (4 fractions) ILBT by iridium
      192 with remote after loading. ILBT was performed using percutaneous transhepatic
      biliary drainage (PTBD) route. Uncovered metallic stents (UMS) were inserted into
      non-resected patients with obstructive jaundice, with the exception of four
      patients who received percutaneous transhepatic biliary drainage only. UMS were
      placed endoscopically or percutaneously, depending on the initial drainage
      procedure. The primary endpoints were patient death or stent occlusion. Survival
      time of patients in the radiotherapy group was compared with that of patients in
      the resection and BSC groups. Stent patency was compared in the radiotherapy and
      BSC groups. RESULTS: No statistically significant differences in patient
      characteristics were found among the resection, radiotherapy, and BSC groups.
      Three patients in the radiotherapy group and one in the BSC group did not receive
      UMS insertion but received PTBD alone; cholangitis occurred after endoscopic
      stenting, and patients were treated with PTBD. A total of 16 patients were
      administered additional systemic chemotherapy (5-fluorouracil-based regimen in 9,
      S-1 in 6, and gemcitabine in 1). Overall survival varied significantly among
      groups, with median survival times of 48.7 mo in the surgery group, 22.1 mo in
      the radiotherapy group, and 5.7 mo in the BSC group. Patients who underwent
      curative resection survived significantly longer than those who were not
      candidates for surgery (P = 0.0076). Cumulative survival in the radiotherapy
      group was significantly longer than in the BSC group (P = 0.0031), but did not
      differ significantly from those in the non-resection group. Furthermore, the
      median survival time of patients in the radiotherapy group who were considered
      for possible resection (excluding the seven patients who were not candidates for
      surgery due to comorbid disease or age) was 25.9 mo. Stent patency was evaluated
      only in the 24 patients who received a metallic stent. Stent patency was
      significantly longer in the radiotherapy than in the BSC group (P = 0.0165).
      Biliary drainage was not eliminated in any patient. To determine the efficacy of
      ILBT, we compared survival time and stent patency in the EBRT alone and EBRT plus
      ILBT groups. However, we found no significant difference in survival time between
      groups or for stent patencies. Hemorrhagic gastroduodenal ulcers were observed in
      5 patients (17.9%), three in the EBRT plus ILBT group and two in the EBRT alone
      group. Ulcers occurred 5 mo, 7 mo, 8 mo, 16 mo, and 29 mo following radiotherapy.
      All patients required hospitalization, but blood transfusions were unnecessary.
      All 5 patients recovered following the administration of anti-ulcer medication.
      CONCLUSION: Radiotherapy improved patient prognosis and the patency of uncovered
      metallic stents in patients with locally advanced hilar cholangiocarcinoma, but
      ILBT provided no additional benefits.

PMID- 22654428
TI  - Comparison of percutaneous transhepatic portal vein embolization and unilateral
      portal vein ligation.
AB  - AIM: To compare the effect of percutaneous transhepatic portal vein embolization
      (PTPE) and unilateral portal vein ligation (PVL) on hepatic hemodynamics and
      right hepatic lobe (RHL) atrophy. METHODS: Between March 2005 and March 2009, 13
      cases were selected for PTPE (n = 9) and PVL (n = 4) in the RHL. The PTPE group
      included hilar bile duct carcinoma (n = 2), intrahepatic cholangiocarcinoma (n =
      2), hepatocellular carcinoma (n = 2) and liver metastasis (n = 3). The PVL group
      included hepatocellular carcinoma (n = 2) and liver metastasis (n = 2). In
      addition, observation of postoperative hepatic hemodynamics obtained from
      computed tomography and Doppler ultrasonography was compared between the two
      groups. RESULTS: Mean ages in the two groups were 58.9 +/- 2.9 years (PVL group)
      vs 69.7 +/- 3.2 years (PTPE group), which was a significant difference (P =
      0.0002). Among the indicators of liver function, including serum albumin, serum
      bilirubin, aspartate aminotransferase, alanine aminotransferase, platelets and
      indocyanine green retention rate at 15 min, no significant differences were
      observed between the two groups. Preoperative RHL volumes in the PTPE and PVL
      groups were estimated to be 804.9 +/- 181.1 mL and 813.3 +/- 129.7 mL,
      respectively, with volume rates of 68.9% +/- 2.8% and 69.2% +/- 4.2%,
      respectively. There were no significant differences in RHL volumes (P = 0.83) and
      RHL volume rates (P = 0.94), respectively. At 1 mo after PTPE or PVL,
      postoperative RHL volumes in the PTPE and PVL groups were estimated to be 638.4
      +/- 153.6 mL and 749.8 +/- 121.9 mL, respectively, with no significant difference
      (P = 0.14). Postoperative RHL volume rates in the PTPE and PVL groups were
      estimated to be 54.6% +/- 4.2% and 63.7% +/- 3.9%, respectively, which was a
      significant difference (P = 0.0056). At 1 mo after the operation, the liver
      volume atrophy rate was 14.3% +/- 2.3% in the PTPE group and 5.4% +/- 1.6% in the
      PVL group, which was a significant difference (P = 0.0061). CONCLUSION: PTPE is a
      more effective procedure than PVL because PTPE is able to occlude completely the
      portal branch throughout the right peripheral vein.

PMID- 22654430
TI  - Hexahydrocurcumin enhances inhibitory effect of 5-fluorouracil on HT-29 human
      colon cancer cells.
AB  - AIM: To investigate the ability of hexahydrocurcumin (HHC) to enhance 5
      fluorouracil (5-FU) in inhibiting the growth of HT-29 cells by focusing on
      cyclooxygenase (COX)-2 expression. METHODS: Antiproliferative effects of HHC and
      5-FU, alone and in combination, on growth of HT-29 human colon cancer cells were
      assessed using 5-diphenyltetrazolium bromide (MTT) reduction assay. In
      combination treatment, low doses of 5-FU were used combined with various
      concentrations of HHC to minimize the toxicity and side effects of 5-FU. The
      therapeutic effects of these drugs on down-regulation of COX-2 mRNA and protein
      expression were examined using semi-quantitative reverse transcription-polymerase
      chain reaction (RT-PCR) and Western blotting analysis. RESULTS: MTT reduction
      assay indicated that HHC alone markedly decreased the viability of HT-29 human
      colon cancer cells compared to control. Semi-quantitative RT-PCR analysis
      indicated that HHC is a selective COX-2 inhibitor. This finding was supported by
      the observation that HHC significantly down-regulates COX-2 mRNA expression
      compared to the control (control: 100.05% +/- 0.03% vs HHC: 61.01% +/- 0.35%, P <
      0.05) but does not alter COX-1 mRNA. In combined treatment, addition of HHC to a
      low dose of 5-FU exerts a synergistic effect against the growth of HT-29 cells by
      markedly reducing cell viability to a greater degree than monotherapy. Semi
      quantitative RT-PCR indicated that 5-FU at the concentration of 5 MUmol/L in
      combination with HHC at the concentration of 25 MUmol/L significantly down
      regulates COX-2 mRNA expression when compared with values in cells treated with 5
      FU or HHC alone (HHC + 5-FU: 31.93% +/- 5.69%, 5-FU: 100.66% +/- 4.52% vs HHC:
      61.01% +/- 0.35%, P < 0.05). CONCLUSION: HHC together with 5-FU exerts a
      synergistic effect and may prove chemotherapeutically useful in treating human
      colon cancer.

PMID- 22654429
TI  - Comparison of sequential and 7-, 10-, 14-d triple therapy for Helicobacter pylori
      infection.
AB  - AIM: To compare the effectiveness of sequential therapy for Helicobacter pylori
      (H. pylori) infection with that of triple therapy of varying durations. METHODS:
      The 460 patients enrolled in this study had H. pylori-associated gastritis or a
      gastric or duodenal ulcer. After screening, H. pylori-infected patients were
      randomly assigned to receive either conventional triple therapy for 7, 10 or 14
      d, or a new 10-d sequential therapy. Each of the 4 treatment groups included 115
      patients. The outcomes of eradication therapy were assessed 4 wk after treatment
      by the urea breath test and histology. RESULTS: The overall eradication rate was
      81.0%, and eradication rates were 75.7% for 7-d conventional triple therapy,
      81.9% for 10-d conventional triple therapy, 84.4% for 14-d conventional triple
      therapy, and 82.0% for 10-d sequential therapy. Neither intention-to-treat
      analysis nor per protocol analysis showed significant differences in eradication
      rates using sequential therapy or the standard triple therapy (P = 0.416 and P =
      0.405, respectively). CONCLUSION: There are no significant differences between 10
      d sequential eradication therapy for H. pylori and any duration of standard
      triple treatment in Korean patients.

PMID- 22654431
TI  - A randomized open-label trial of on-demand rabeprazole vs ranitidine for patients
      with non-erosive reflux disease.
AB  - AIM: To compare the efficacy of the proton-pump inhibitor, rabeprazole, with that
      of the H2-receptor antagonist, ranitidine, as on-demand therapy for relieving
      symptoms associated with non-erosive reflux disease (NERD). METHODS: This is a
      single center, prospective, randomized, open-label trial of on-demand therapy
      with rabeprazole (group A) vs ranitidine (group B) for 4 wk. Eighty-three
      patients who presented to the American University of Beirut Medical Center with
      persistent gastroesophageal reflux disease (GERD) symptoms and a normal upper
      gastrointestinal endoscopy were eligible for the study. Patients in group A (n =
      44) were allowed a maximum rabeprazole dose of 20 mg twice daily, while those in
      group B (n = 39) were allowed a maximum ranitidine dose of 300 mg twice daily.
      Efficacy was assessed by patient evaluation of global symptom relief, scores of
      the SF-36 quality of life (QoL) questionnaires, total number of pills used, and
      number of medication-free days. RESULTS: Among the 83 patients who were enrolled
      in the study, 76 patients (40 in the rabeprazole group and 36 in the ranitidine
      group) completed the 4-wk trial. Baseline characteristics were comparable between
      both groups. After 4 wk, there was no significant difference in the subjective
      global symptom relief between the rabeprazole and the ranitidine groups (71.4% vs
      65.4%, respectively; P = 0.9). There were no statistically significant
      differences between mean cumulative scores of the SF-36 QoL questionnaire for the
      two study groups (rabeprazole 22.40 +/- 27.53 vs ranitidine 17.28 +/- 37.06; P =
      0.582). There was no significant difference in the mean number of pills used
      (rabeprazole 35.70 +/- 29.75 vs ranitidine 32.86 +/- 26.98; P = 0.66). There was
      also no statistically significant difference in the mean number of medication
      free days between both groups. CONCLUSION: Rabeprazole has a comparable efficacy
      compared to ranitidine when given on-demand for the treatment of NERD. Both
      medications were associated with improved quality of life.

PMID- 22654432
TI  - Poorly expandable common bile duct with stones on endoscopic retrograde
      cholangiography.
AB  - AIM: To describe characteristics of a poorly expandable (PE) common bile duct
      (CBD) with stones on endoscopic retrograde cholangiography. METHODS: A PE bile
      duct was characterized by a rigid and relatively narrowed distal CBD with
      retrograde dilatation of the non-PE segment. Between 2003 and 2006, endoscopic
      retrograde cholangiography (ERC) images and chart reviews of 1213 patients with
      newly diagnosed CBD stones were obtained from the computer database of
      Therapeutic Endoscopic Center in Chang Gung Memorial Hospital. Patients with
      characteristic PE bile duct on ERC were identified from the database. Data of the
      patients as well as the safety and technical success of therapeutic ERC were
      collected and analyzed retrospectively. RESULTS: A total of 30 patients with CBD
      stones and characteristic PE segments were enrolled in this study. The median
      patient age was 45 years (range, 20 to 92 years); 66.7% of the patients were men.
      The diameters of the widest non-PE CBD segment, the PE segment, and the largest
      stone were 14.3 +/- 4.9 mm, 5.8 +/- 1.6 mm, and 11.2 +/- 4.7 mm, respectively.
      The length of the PE segment was 39.7 +/- 15.4 mm (range, 12.3 mm to 70.9 mm). To
      remove the CBD stone(s) completely, mechanical lithotripsy was required in 25
      (83.3%) patients even though the stone size was not as large as were the
      difficult stones that have been described in the literature. The stone size and
      stone/PE segment diameter ratio were associated with the need for lithotripsy.
      Post-ERC complications occurred in 4 cases: pancreatitis in 1, cholangitis in 2,
      and an impacted Dormia basket with cholangitis in 1. Two (6.7%) of the 28
      patients developed recurrent CBD stones at follow-up (50 +/- 14 mo) and were
      successfully managed with therapeutic ERC. CONCLUSION: Patients with a PE duct
      frequently require mechanical lithotripsy for stones extraction. To retrieve
      stones successfully and avoid complications, these patients should be identified
      during ERC.

PMID- 22654433
TI  - Prognosis of HER2 over-expressing gastric cancer patients with liver metastasis.
AB  - AIM: To study the risk factors for liver metastasis and the prognosis in patients
      with human epidermal growth factor receptor 2 (HER2) over-expressing gastric
      cancer (GC). METHODS: A total of 84 GC patients recruited from the General
      Hospital of the People's Liberation Army (PLA) between 2003 and 2010 were
      randomly enrolled in this study. HER2 expression was detected by
      immunohistochemistry in 84 GC patients with liver metastases. The study group
      consisted of 66 men and 18 women, with an average age of 54 years (range: 19-74
      years). Liver metastasis was diagnosed by magnetic resonance imaging or computed
      tomography. Patients were followed-up and predictive factors of liver metastasis
      were evaluated. RESULTS: The median follow-up period was 47 mo (range: 6-85 mo).
      The characteristics of 35 (25.7%) patients with HER2 over-expression of liver
      metastatic GC are presented. HER2 over-expression was detected in 23 out of 49
      (46.9%) patients with intestinal GC, and 9 out of 35 (25.7%) patients with
      diffuse GC. 29 out of 59 (49.2%) patients aged < 60 years were HER2-positive,
      while 8 out of 25 (32%) patients aged >= 60 were HER2-positive; a significant
      difference (P < 0.05). Univariate analysis (log-rank test) showed that HER2 over
      expression, sex, Lauren classification, differentiation and disease-free interval
      were correlated with poor survival (P < 0.05). Survival analysis with a survival
      curve showed that HER2 over-expression was significantly relevant, with a reduced
      survival time in GC patients with liver metastases (P < 0.01). 2-year survival
      was not associated with the patient's age. A disease-free survival longer than 12
      mo has a significant association with extended overall survival (OS) in GC
      patients with liver metastases. The median survival time after the diagnosis of
      liver metastases was 18 mo [95% confidence interval (CI): 9.07-26.94] among HER2
      positive GC patients with liver metastases. In comparison, for 49 (69.4%) out of
      84 HER2 negative patients with liver metastatic GC, the median survival time was
      47 mo (95% CI: 19.37-74.63). In patients with HER2 positive liver metastatic GC,
      the median OS was significantly shorter than in HER2 negative patients (median,
      20.32 mo; 95% CI: 16.51-24.13 vs median, 50.14 mo; 95% CI: 37.83-62.45; P <
      0.01). CONCLUSION: HER2 over-expressing GC patients with liver metastases have a
      poor prognosis. Overall survival was significantly lower in HER2 positive
      patients. HER2-overexpression is correlated with a lower survival rate.

PMID- 22654434
TI  - Glypican-3 expression and its relationship with recurrence of HCC after liver
      transplantation.
AB  - AIM: To investigate the diagnostic value of glypican-3 (GPC3) and its
      relationship with hepatocellular carcinoma (HCC) recurrence after liver
      transplantation. METHODS: HCC tissue samples (n = 31) obtained from patients who
      had undergone liver transplantation were analyzed. GPC3 mRNA and protein
      expression were analyzed by TaqMan real-time reverse transcription-polymerase
      chain reaction and immunohistochemistry. Correlation between the GPC3 expression
      and clinicopathological features was analyzed. The potential prognostic value of
      GPC3 was investigated by comparing recurrence-free survival between HCC patients
      with and without GPC3 expression. RESULTS: Using a cutoff value of 3.5 * 10-2, 20
      of 31 cancerous tissues had expression values of > 3.5 * 10-2, whereas 3 of 31
      adjacent non-neoplastic parenchyma and 0 of 20 control liver tissues had
      expression values of > 3.5 * 10-2 (P < 0.001). GPC3 protein was immunoexpressed
      in 68% of cancerous tissues, but not in adjacent non-neoplastic parenchyma and
      control liver tissues. Vascular invasion was significantly related to GPC3
      expression (P < 0.05). Recurrence-free survival was significantly longer for
      patients without GPC3 mRNA overexpression (> 3.5 * 10-2) and those without
      vascular invasion (P < 0.05 for both). CONCLUSION: GPC3 expression may serve as a
      valuable diagnostic marker for HCC. GPC3 mRNA overexpression may be an adverse
      indicator for HCC patients after liver transplantation.

PMID- 22654435
TI  - Salvage liver transplantation in the treatment of hepatocellular carcinoma: a
      meta-analysis.
AB  - AIM: To evaluate survival and recurrence after salvage liver transplantation
      (SLT) for the treatment of hepatocellular carcinoma (HCC) compared with primary
      liver transplantation (PLT) using a meta-analysis. METHODS: Literature on SLT
      versus PLT for the treatment of HCC published between 1966 and July 2011 was
      retrieved. A meta-analysis was conducted to estimate pooled survival and disease
      free rates. A fixed or random-effect model was established to collect the data.
      RESULTS: The differences in overall survival and disease-free survival rates at 1
      year, 3-year and 5-year survival rates were not statistically significant between
      SLT group and PLT group (P > 0.05). After stratifying the various studies by
      donor source and Milan criteria, we found that: (1) Living donor liver
      transplantation recipients had significantly higher 1-year survival rate, lower 3
      year and 5-year survival rates compared with deceased-donor liver transplantation
      (DDLT) recipients. And in DDLT recipients they had better 1-year and 5-year
      disease-free survival rate in SLT group; and (2) No difference was seen in 1
      year, 3-year and 5-year survival rates between two groups who beyond Milan
      criteria at the time of liver transplantation. CONCLUSION: SLT can be effectively
      performed for patients with recurrence or deterioration of liver function after
      hepatectomy for HCC. It does not increase the perioperative mortality and has a
      similar long-term survival rates compared to PLT.

PMID- 22654436
TI  - Reduced Popdc3 expression correlates with high risk and poor survival in patients
      with gastric cancer.
AB  - AIM: To investigate the expression of Popeye domain containing 3 (Popdc3) and its
      correlation with clinicopathological features and prognosis of gastric cancer.
      METHODS: The method of immunohistochemistry was used to investigate the
      expression of Popdc3 in 306 cases of human gastric cancer and 84 noncancerous
      gastric tissues. Simultaneously, the relationship between Popdc3 expression and
      the survival of the patients was retrospectively analyzed. RESULTS: Popdc3 was
      detected in 72 (85.71%) of 84 human nontumor mucosa. High expression of Popdc3
      protein was detected in 78 (25.49%) of 306 human gastric cancer cases, and low
      expression was detected in 228 (74.51%). Low expression of Popdc3 correlated with
      depth of invasion (P < 0.0001), regional lymph nodes (P < 0.0001) and distant
      metastasis (P = 0.02), and tumor, nodes, metastasis (TNM) stages (P < 0.0001). On
      multivariate analysis, only the patient's gender, regional lymph node metastasis,
      distant metastasis, TNM stages, and the expression of Popdc3 were independent
      prognostic factors in patients with gastric cancer. The Kaplan-Meier plot showed
      that low Popdc3 expression had a much more significant effect on the survival of
      those patients with early-stage tumors (chi2 = 104.741, P < 0.0001), with a >
      51.9% reduction in the three-year survival compared with high Popdc3 expression.
      In late stages, the difference was also significant (chi2 = 5.930, P = 0.015),
      with a 32.6% reduction in the three-year survival. CONCLUSION: Reduced expression
      of Popdc3 may play a significant role in the carcinogenesis and progression of
      gastric cancer. Popdc3 may be an independent prognostic factor.

PMID- 22654437
TI  - Giardia infection: protein-losing enteropathy in an adult with immunodeficiency.
AB  - The case of a 52-year-old woman with a past history of thymoma resection who
      presented with chronic diarrhea and generalized edema is the focal point of this
      article. A diagnosis of Giardia lamblia infection was established, which was
      complicated by protein-losing enteropathy and severely low serum protein level in
      a patient with no urinary protein loss and normal liver function. After anti
      helmintic treatment, there was recovery from hypoalbuminemia, though
      immunoglobulins persisted at low serum levels leading to the hypothesis of an
      immune system disorder. Good's syndrome is a rare cause of immunodeficiency
      characterized by the association of hypogammaglobulinemia and thymoma. This
      primary immune disorder may be complicated by severe infectious diarrhea
      secondary to disabled humoral and cellular immune response. This is the first
      description in the literature of an adult patient with an immunodeficiency
      syndrome who presented with protein-losing enteropathy secondary to giardiasis.

PMID- 22654438
TI  - An unusual enteropathy-associated T-cell lymphoma with MYC translocation arising
      in a Japanese patient: a case report.
AB  - Enteropathy-associated T-cell lymphoma (EATL) is a rare peripheral T-cell
      lymphoma classified into 2 types, with or without celiac disease, based on
      histology. Type 2 EATL is less commonly associated with celiac disease, in which
      cells are characterized by being monomorphic and small- to medium-sized. Cells
      are characterized by CD8 and CD56 expression and c-MYC oncogene locus gain. We
      present an atypical case of type 2 EATL in the jejunum, with human T-lymphotropic
      virus-1 that was CD4- CD8+ CD56- CD30- CD25- TIA-1+ and granzyme B+ on
      immunohistological staining. It also displayed translocation of chromosome 8p24
      (c-MYC), as determined by fluorescent in situ hybridization. Mucosal spreading
      and intraepithelial invasion by lymphoma with villous atrophy were detected
      adjacent to the mucosal layer. The lymphoma may be derived from intraepithelial
      CD8+ T cells, similar to celiac disease.

PMID- 22654439
TI  - Spontaneous perforation of an intramural rectal hematoma: report of a case.
AB  - Spontaneous hematomas are rare and most occur secondary to hematologic disorders
      or during anticoagulant therapy. Most spontaneous hematomas occur above the
      sigmoid colon, and rarely in the rectum. Herein we present the case of a patient
      with a spontaneous perforating hematoma of the rectum who presented with severe
      abdominal pain after a bloody stool. The hemoglobin level decreased by 33 g/L
      within 20 h. An abdominal sonogram showed a hydrops in the lower abdomen with a
      maximum depth of 7.0 cm. A hematoma, 8 cm * 6 cm * 5 cm in size, was noted intra
      operatively in the rectosigmoid junction, with a 1.5-cm perforation in the
      hematoma and active hemorrhage. Thus, a partial rectectomy and sigmoidostomy were
      performed. Three months later, a second operative procedure to re-establish
      intestinal continuity was performed. The patient is in good condition 12 mo after
      the last surgery. In addition to this case, the causes of spontaneous perforating
      hematomas and the treatment are discussed.

PMID- 22654440
TI  - Does antioxidant therapy influence every aspect of quality of life?
AB  - To present problems that might severely impact the conclusions drawn by the
      authors of an article on antioxidant treatment in chronic pancreatitis (World J
      Gastroenterol 2010; 16: 4066-4071). We analyzed and discussed this paper by Shah
      et al, and found that promising as it is, this study has some methodological
      shortcomings, such as: cross-sectional nature of the study, lack of initial
      evaluations of quality of life and regular follow-ups to determine the dynamics
      and real directions of changes in quality of life. We therefore concluded that
      the results of the study by Shah et al are biased and, although very promising,
      should not be considered as scientifically relevant.

PMID- 22654441
TI  - T cell immunopathogenesis and immunotherapeutic strategies for chronic hepatitis
      B virus infection.
AB  - Hepatitis B is caused by the host immune response and T cells play a major role
      in the immunopathogenesis. More importantly, T cells not only destroy hepatocytes
      infected by hepatitis B virus (HBV), but also control HBV replication or
      eradicate HBV in a noncytolytic manner. Therefore, analysis of T cell immune
      response during acute and chronic HBV infection is important to develop a
      strategy for successful viral control, which could lead to immunotherapy for
      terminating persistent HBV infection. There have been many attempts at
      immunotherapy for chronic HBV infection, and some have shown promising results.
      High viral load has been shown to suppress antiviral immune responses and
      immunoinhibitory signals have been recently elucidated, therefore, viral
      suppression by nucleos(t)ide analogs, stimulation of antiviral immune response,
      and suppression of the immunoinhibitory signals must be combined to achieve
      desirable antiviral effects.

PMID- 22654442
TI  - Serrated polyposis syndrome: molecular, pathological and clinical aspects.
AB  - Hyperplastic polyps have traditionally been considered not to have malignant
      potential. New pathological classification of serrated polyps and recent
      discoveries about the serrated pathway of carcinogenesis have revolutionized the
      concepts and revitalized the research in this area. Until recently, it has been
      thought that most colorectal cancers arise from conventional adenomas via the
      traditional tumor suppressor pathway initiated by a mutation of the APC gene, but
      it has been found that this pathway accounts for only approximately 70%-80% of
      colorectal cancer (CRC) cases. The majority of the remaining colorectal cancer
      cases follow an alternative pathway leading to CpG island methylator phenotype
      carcinoma with BRAF mutation and with or without microsatellite instability. The
      mechanism of carcinomas arising from this alternative pathway seems to begin with
      an activating mutation of the BRAF oncogene. Serrated polyposis syndrome is a
      relatively rare condition characterized by multiple and/or large serrated polyps
      of the colon. Clinical characteristics, etiology and relationship of serrated
      polyposis syndrome to CRC have not been clarified yet. Patients with this
      syndrome show a high risk of CRC and both sporadic and hereditary cases have been
      described. Clinical criteria have been used for diagnosis and frequent
      colonoscopy surveillance should be performed in order to prevent colorectal
      cancer. In this review, we try to gather new insights into the molecular
      pathogenesis of serrated polyps in order to understand their possible clinical
      implications and to make an approach to the management of this syndrome.

PMID- 22654443
TI  - Globus pharyngeus: a review of its etiology, diagnosis and treatment.
AB  - Globus is a persistent or intermittent non-painful sensation of a lump or foreign
      body in the throat. It is a commonly encountered clinical condition that is
      usually long-lasting, difficult to treat, and has a tendency to recur.
      Furthermore, due to the uncertain etiology of globus, it remains difficult to
      establish standard investigation and treatment strategies for affected patients.
      As a first step for managing globus, careful history taking and nasolaryngoscopy
      are essential. Given the benign nature of the condition and the recent notion
      that gastroesophageal reflux disease is a major cause of globus, empirical
      therapy with a high dose of proton pump inhibitors is reasonable for patients
      with typical globus. If patients are nonresponsive to this therapy, definitive
      assessments such as endoscopy, multichannel intraluminal impedance/pH monitoring,
      and manometry should be considered. Speech and language therapy, anti
      depressants, and cognitive-behavioral therapy can be helpful in patients whose
      symptoms persist despite negative investigations.

PMID- 22654444
TI  - Lactobacillus plantarum B7 inhibits Helicobacter pylori growth and attenuates
      gastric inflammation.
AB  - AIM: To determine the anti-Helicobacter property of Lactobacillus plantarum B7
      (L. plantarum) B7 supernatants in vitro and the protective effects of L.
      plantarum B7 on serum tumor necrosis factor-alpha (TNF-alpha), gastric
      malondialdehyde (MDA) level, apoptosis, and histopathology in Helicobacter pylori
      (H. pylori)-induced gastric inflammation in rats. METHODS: In vitro, the
      inhibition of H. pylori growth was examined using L. plantarum B7 supernatants at
      pH 4 and pH 7 and at the concentration of 1*, 5* and 10* on plates inoculated
      with H. pylori. The inhibitory effect of H. pylori was interpreted by the size of
      the inhibition zone. In vitro, male Sprague-Dawley rats were randomly divided
      into four groups including group 1 (control group), group 2 (H. pylori infected
      group), group 3 (H. pylori infected with L. plantarum B7 10(6) CFUs/mL treated
      group) and group 4 (H. pylori infected with L. plantarum B7 10(10) CFUs/mL
      treated group). One week after H. pylori inoculation, L. plantarum B7 10(6)
      CFUs/mL or 10(10) CFUs/mL were fed once daily to group 3 and group 4,
      respectively, for one week. Blood and gastric samples were collected at the end
      of the study. RESULTS: In vitro, at intact pH 4, mean inhibitory zone diameters
      of 8.5 mm and 13 mm were noted at concentrations of 5* and 10* of L. plantarum B7
      supernatant disks, respectively. At adjusted pH 7, L. plantarum B7 supernatants
      at concentrations of 5* and 10* yielded mean inhibitory zone diameters of 6.5 mm
      and 11 mm, respectively. In the in vitro study, in group 2, stomach
      histopathology revealed mild to moderate H. pylori colonization and inflammation.
      The level of gastric MDA and epithelial cell apoptosis were significantly
      increased compared with group 1. The serum TNF-alpha level was significant
      decreased in group 3 compared with group 2 (P < 0.05). In addition, L. plantarum
      B7 treatments resulted in a significant improvement in stomach pathology, and
      decreased gastric MDA level and apoptotic epithelial cells. CONCLUSION: L.
      plantarum B7 supernatant inhibits H. pylori growth. This inhibition was dose
      dependent and greater at pH 4. Moreover, L. plantarum B7 attenuated H. pylori
      induced gastric inflammation.

PMID- 22654445
TI  - Key factors in developing the trinitrobenzene sulfonic acid-induced post
      inflammatory irritable bowel syndrome model in rats.
AB  - AIM: To investigate the key factors in developing the trinitrobenzene sulfonic
      acid (TNBS)-induced post-inflammatory irritable bowel syndrome (PI-IBS) model in
      rats. METHODS: TNBS was administered to rats at the following conditions: (1)
      with different doses (20, 10, 5 mg/0.8 mL per rat); (2) with same dose in
      different concentrations (20 mg/rat, 25, 50 mg/mL); (3) in different ethanol
      percentage (25%, 50%); and (4) at depth either 4 cm or 8 cm from anus. At 5 d and
      4 wk after TNBS administration, inflammation severity and inflammation resolution
      were evaluated. At 4 and 8 wk after TNBS application, visceral hyperalgesia and
      enterochromaffin (EC) cell hyperplasia were assayed by abdominal withdrawal
      reflex test, silver staining and capillary electrophoresis. RESULTS: Our results
      showed that: (1) TNBS induced dose-dependent acute inflammation and inflammation
      resolution. At 5 d post TNBS, the pathological score and myeloperoxidase (MPO)
      activity in all TNBS treated rats were significantly elevated compared to that of
      the control (9.48 +/- 1.86, 8.18 +/- 0.67, 5.78 +/- 0.77 vs 0, and 3.55 +/- 1.11,
      1.80 +/- 0.82, 0.97 +/- 0.08 unit/mg vs 0.14 +/- 0.01 unit/mg, P < 0.05). At 4 wk
      post TNBS, the pathological score in high and median dose TNBS-treated rats were
      still significantly higher than that of the control (1.52 +/- 0.38 and 0.80 +/-
      0.35 vs 0, P < 0.05); (2) Intracolonic TNBS administration position affected the
      persistence of visceral hyperalgesia. At 4 wk post TNBS, abdominal withdrawal
      reflex (AWR) threshold pressure in all TNBS-treated groups were decreased
      compared to that of the control (21.52 +/- 1.73 and 27.10 +/- 1.94 mmHg vs 34.44
      +/- 1.89 mmHg, P < 0.05). At 8 wk post TNBS, AWR threshold pressure in 8 cm
      administration group was still significantly decreased (23.33 +/- 1.33 mmHg vs
      36.79 +/- 2.29 mmHg, P < 0.05); (3) Ethanol percentage affected the TNBS-induced
      inflammation severity and visceral hyperalgesia. In TNBS-25% ethanol-treated
      group, the pathological score and MPO activity were significantly lowered
      compared to that of the TNBS-50% ethanol-treated group, while AWR threshold
      pressure were significantly elevated (36.33 +/- 0.61 mmHg vs 23.33 +/- 1.33 mmHg,
      P < 0.05); and (4) TNBS (5 mg/0.8 mL per rat, in 50% ethanol, 8 cm from anus)
      treated rats recovered completely from the inflammation with acquired visceral
      hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.
      CONCLUSION: TNBS dosage, concentration, intracolonic administration position, and
      ethanol percentage play important roles in developing visceral hyperalgesia and
      EC cell hyperplasia of TNBS-induced PI-IBS rats.

PMID- 22654446
TI  - Cost-benefit analysis of esophageal cancer endoscopic screening in high-risk
      areas of China.
AB  - AIM: To estimate the cost-benefit of endoscopic screening strategies of
      esophageal cancer (EC) in high-risk areas of China. METHODS: Markov model-based
      analyses were conducted to compare the net present values (NPVs) and the benefit
      cost ratios (BCRs) of 12 EC endoscopic screening strategies. Strategies varied
      according to the targeted screening age, screening frequencies, and follow-up
      intervals. Model parameters were collected from population-based studies in
      China, published literatures, and surveillance data. RESULTS: Compared with non
      screening outcomes, all strategies with hypothetical 100,000 subjects saved life
      years. Among five dominant strategies determined by the incremental cost
      effectiveness analysis, screening once at age 50 years incurred the lowest NPV
      (international dollar-I$55 million) and BCR (2.52). Screening six times between
      40-70 years at a 5-year interval [i.e., six times(40)f-strategy] yielded the
      highest NPV (I$99 million) and BCR (3.06). Compared with six times(40)f-strategy,
      screening thrice between 40-70 years at a 10-year interval resulted in relatively
      lower NPV, but the same BCR. CONCLUSION: EC endoscopic screening is cost
      beneficial in high-risk areas of China. Policy-makers should consider the cost
      benefit, population acceptance, and local economic status when choosing suitable
      screening strategies.

PMID- 22654447
TI  - Cervical inlet patch-optical coherence tomography imaging and clinical
      significance.
AB  - AIM: To demonstrate the feasibility of optical coherence tomography (OCT) imaging
      in differentiating cervical inlet patch (CIP) from normal esophagus, Barrett's
      esophagus (BE), normal stomach and duodenum. METHODS: This study was conducted at
      the Veterans Affairs Boston Healthcare System (VABHS). Patients undergoing
      standard esophagogastroduodenoscopy at VABHS, including one patient with CIP, one
      representative patient with BE and three representative normal subjects were
      included. White light video endoscopy was performed and endoscopic 3D-OCT images
      were obtained in each patient using a prototype OCT system. The OCT imaging probe
      passes through the working channel of the endoscope to enable simultaneous video
      endoscopy and 3D-OCT examination of the human gastrointestinal (GI) tract.
      Standard hematoxylin and eosin (H and E) histology was performed on biopsy or
      endoscopic mucosal resection specimens in order to compare and validate the 3D
      OCT data. RESULTS: CIP was observed from a 68-year old male with gastroesophageal
      reflux disease. The CIP region appeared as a pink circular lesion in the upper
      esophagus under white light endoscopy. OCT imaging over the CIP region showed
      columnar epithelium structure, which clearly contrasted the squamous epithelium
      structure from adjacent normal esophagus. 3D-OCT images obtained from other
      representative patients demonstrated distinctive patterns of the normal
      esophagus, BE, normal stomach, and normal duodenum bulb. Microstructures, such as
      squamous epithelium, lamina propria, muscularis mucosa, muscularis propria,
      esophageal glands, Barrett's glands, gastric mucosa, gastric glands, and
      intestinal mucosal villi were clearly observed with OCT and matched with H and E
      histology. These results demonstrated the feasibility of using OCT to evaluate GI
      tissue morphology in situ and in real-time. CONCLUSION: We demonstrate in situ
      evaluation of CIP microstructures using 3D-OCT, which may be a useful tool for
      future diagnosis and follow-up of patients with CIP.

PMID- 22654448
TI  - Endomysial antibodies predict celiac disease irrespective of the titers or
      clinical presentation.
AB  - AIM: To investigate the association between serum antibody levels and a
      subsequent celiac disease diagnosis in a large series of children and adults.
      METHODS: Besides subjects with classical gastrointestinal presentation of celiac
      disease, the study cohort included a substantial number of individuals with
      extraintestinal symptoms and those found by screening in at-risk groups.
      Altogether 405 patients underwent clinical, serological and histological
      evaluations. After collection of data, the antibody values were further graded as
      low [endomysial (EmA) 1:5-200, transglutaminase 2 antibodies (TG2-ab) 5.0-30.0
      U/L] and high (EmA 1: >= 500, TG2-ab >= 30.0 U/L), and the serological results
      were compared with the small intestinal mucosal histology and clinical
      presentation. RESULTS: In total, 79% of the subjects with low and 94% of those
      with high serum EmA titers showed small-bowel mucosal villous atrophy.
      Furthermore, 96% of the 47 EmA positive subjects who had normal mucosal villi and
      remained on follow-up either subsequently developed mucosal atrophy while on a
      gluten-containing diet, or responded positively to a gluten-free diet.
      CONCLUSION: Irrespective of the initial serum titers or clinical presentation,
      EmA positivity as such is a very strong predictor of a subsequent celiac disease
      diagnosis.

PMID- 22654449
TI  - Efficacy of mosapride citrate with polyethylene glycol solution for colonoscopy
      preparation.
AB  - AIM: To evaluate the efficacy and safety of adjunctive mosapride citrate for
      bowel preparation before colonoscopy. METHODS: We conducted a randomized, double
      blind, placebo-controlled study with mosapride in addition to polyethylene glycol
      (PEG)-electrolyte solution. Of 250 patients undergoing colonoscopy, 124 were
      randomized to receive 2 L PEG plus 15 mg of mosapride citrate (mosapride group),
      and 126 received 2 L PEG plus placebo (placebo group). Patients completed a
      questionnaire reporting the acceptability and tolerability of the bowel
      preparation process. The efficacy of bowel preparation was assessed by
      colonoscopists using a 5-point scale based on Aronchick's criteria. The primary
      end point was optimal bowel preparation rates (scores of excellent/good/fair vs
      poor/inadequate). RESULTS: A total of 249 patients were included in the analysis.
      In the mosapride group, optimal bowel preparation rates were significantly higher
      in the left colon compared with the placebo group (78.2% vs 65.6%, P < 0.05), but
      not in the right colon (76.5% vs 66.4%, P = 0.08). After excluding patients with
      severe constipation, there was a significant difference in bowel preparation in
      both the left and right colon (82.4% vs 66.7%, 80.8% vs 67.5%, P < 0.05, P <
      0.01). The incidence of adverse events was similar in both groups. Among the
      subgroup who had previous colonoscopy experience, a significantly higher number
      of patients in the mosapride group felt that the current preparation was easier
      compared with patients in the placebo group (34/72 patients vs 24/74 patients, P
      < 0.05). CONCLUSION: Mosapride citrate may be an effective and safe adjunct to
      PEG-electrolyte solution that leads to improved quality of bowel preparation,
      especially in patients without severe constipation.

PMID- 22654450
TI  - Endoscopic ultrasound-guided biliary drainage with placement of a fully covered
      metal stent for malignant biliary obstruction.
AB  - AIM: To determine the utility of endoscopic ultrasound-guided biliary drainage
      (EUS-BD) with a fully covered self-expandable metal stent for managing malignant
      biliary stricture. METHODS: We collected data from 13 patients who presented with
      malignant biliary obstruction and underwent EUS-BD with a nitinol fully covered
      self-expandable metal stent when endoscopic retrograde cholangiopancreatography
      (ERCP) fails. EUS-guided choledochoduodenostomy (EUS-CD) and EUS-guided
      hepaticogastrostomy (EUS-HG) was performed in 9 patients and 4 patients,
      respectively. RESULTS: The technical and functional success rate was 92.3%
      (12/13) and 91.7% (11/12), respectively. Using an intrahepatic approach (EUS-HG,
      n = 4), there was mild peritonitis (n = 1) and migration of the metal stent to
      the stomach (n = 1). With an extrahepatic approach (EUS-CD, n = 10), there was
      pneumoperitoneum (n = 2), migration (n = 2), and mild peritonitis (n = 1). All
      patients were managed conservatively with antibiotics. During follow-up (range, 1
      12 mo), there was re-intervention (4/13 cases, 30.7%) necessitated by stent
      migration (n = 2) and stent occlusion (n = 2). CONCLUSION: EUS-BD with a nitinol
      fully covered self-expandable metal stent may be a feasible and effective
      treatment option in patients with malignant biliary obstruction when ERCP fails.

PMID- 22654451
TI  - Concomitant lung metastasis in patients with advanced hepatocellular carcinoma.
AB  - AIM: To investigate the clinical features and prognostic factors of advanced
      hepatocellular carcinoma (HCC) patients presenting with lung metastasis at
      initial diagnosis. METHODS: Between 2001 and 2010, we recruited 76 consecutive
      HCC patients initially presenting with lung metastasis, without co-existing
      metastasis from other sites. These patients were divided into three groups:
      untreated group (n = 22), single treatment group (n = 19), and combined treatment
      group (n = 35). RESULTS: Metastasis of bilateral lung lobes was common and noted
      in 35 patients (46.1%), and most of patients (59/76, 77.6%) presented with
      multiple lung metastatic nodules. Nineteen patients (25.0%) received single
      method treatment, including hepatectomy in 4, transcatheter arterial
      chemoembolization in 6, radiotherapy in 5, and oral sorafenib in 4. Thirty-five
      patients (46.1%) received combined treatment modalities. The overall median
      survival of the all patients was 8.7 +/- 0.6 mo; 4.1 +/- 0.3, 6.3 +/- 2.5 and
      18.6 +/- 3.9 mo, respectively in the untreated group, single treatment group and
      combined treatment group, respectively, with a significant difference (log-rank
      test, P < 0.001). Multivariate analysis revealed that Child-Pugh score, the
      absence or presence of portal vein tumor thrombus, and treatment modality were
      three independent prognostic factors affecting survival of patients with advanced
      HCC and concomitant lung metastasis. CONCLUSION: Combined treatment modalities
      tend to result in a better survival as compared with the conservative treatment
      or single treatment modality for HCC patients initially presenting with lung
      metastasis.

PMID- 22654452
TI  - Detection of eukaryotic translation initiation factor 4E and its clinical
      significance in hepatocellular carcinoma.
AB  - AIM: To study the expression of eukaryotic translation initiation factor 4E
      (eIF4E), which is closely correlated with malignant tumors, and its relationship
      to prognosis in hepatocellular carcinoma. METHODS: Western blotting was performed
      to quantify the elF4E protein expression in the normal human liver cell line L02
      and the hepatoma cell lines Hep3B, HepG2, and Huh7. Forty-six hepatocellular
      carcinoma samples with complete clinical data were obtained from Changzheng
      Hospital during the period of December 2008 to July 2009. The expression of eIF4E
      in the tumor samples and their adjacent tissues were detected by
      immunohistochemistry. The relationship between the test results and
      hepatocellular carcinoma (HCC) prognosis was statistically analysed by using a
      COX proportional hazard model. RESULTS: Western blotting analysis showed that
      there were distinct eIF4E protein bands in all three of the hepatoma cell lines.
      In particular, the HepG2 cell line had the highest level of eIF4E protein
      expression. The L02 cell group had a low eIF4E expression. Immunohistochemical
      assay showed that there were 32 cases in which the tumour tissue expression was
      higher than their adjacent tissues, accounting for 69.57%. There were also 14
      cases in which the tumour tissue expression was lower or no significant
      difference was found, accounting for 30.43%. COX proportional hazards model
      analysis showed that HCC prognosis was related to the depth of invasion, the
      overexpression of eIF4E and p53, possibly as independent HCC prognostic
      predictors. CONCLUSION: In summary, eIF4E expression is associated with liver
      cancer, and patients with high eIF4E expression levels have a higher risk of
      recurrence.

PMID- 22654454
TI  - Serum inter-cellular adhesion molecule 1 is an early marker of diagnosis and
      prediction of severe acute pancreatitis.
AB  - AIM: To determine if serum inter-cellular adhesion molecule 1 (ICAM-1) is an
      early marker of the diagnosis and prediction of severe acute pancreatitis (SAP)
      within 24 h of onset of pain, and to compare the sensitivity, specificity and
      prognostic value of this test with those of acute physiology and chronic health
      evaluation (APACHE) II score and interleukin-6 (IL-6). METHODS: Patients with
      acute pancreatitis (AP) were divided into two groups according to the Ranson's
      criteria: mild acute pancreatitis (MAP) group and SAP group. Serum ICAM-1, APACHE
      II and IL-6 levels were detected in all the patients. The sensitivity,
      specificity and prognostic value of the ICAM-1, APACHE II score and IL-6 were
      evaluated. RESULTS: The ICAM-1 level in 36 patients with SAP within 24 h of onset
      of pain was increased and was significantly higher than that in the 50 patients
      with MAP and the 15 healthy volunteers (P < 0.01). The ICAM-1 level (25 ng/mL)
      was chosen as the optimum cutoff to distinguish SAP from MAP, and the
      sensitivity, specificity, positive predictive value, negative predictive value
      (NPV), positive likelihood ratio and negative likelihood ratio were 61.11%,
      71.42%, 0.6111, 0.7142, 2.1382 and 0.5445, respectively. The area under the curve
      demonstrated that the prognostic accuracy of ICAM-1 (0.712) was similar to the
      APACHE-II scoring system (0.770) and superior to IL-6 (0.508) in distinguishing
      SAP from MAP. CONCLUSION: ICAM-1 test is a simple, rapid and reliable method in
      clinical practice. It is an early marker of diagnosis and prediction of SAP
      within the first 24 h after onset of pain or on admission. As it has a relatively
      low NPV and does not allow it to be a stand-alone test for the diagnosis of AP,
      other conventional diagnostic tests are required.

PMID- 22654453
TI  - Association between body mass index and erosive esophagitis: a meta-analysis.
AB  - AIM: To conduct a meta-analysis to estimate the determinants of the association
      between erosive esophagitis (EE) and body mass index (BMI). METHODS: We
      identified the studies using PubMed. Studies were selected for analysis based on
      certain inclusion and exclusion criteria. Data were extracted from each study on
      the basis of predefined items. Meta-analyses were performed to verify the risk
      factors, such as obesity and gender. RESULTS: Twenty-one studies were included in
      this systematic review. These studies demonstrated an association between
      increasing BMI and the presence of EE [95% confidence interval (CI): 1.35-1.88,
      overweight, odds ratio (OR) = 1.60, P value homogeneity = 0.003, 95% CI: 1.65
      2.55, obese, OR = 2.05, P < 0.01]. The heterogeneity disappeared by stratifying
      for gender. No publication bias was observed in this meta-analysis by the Egger
      method. CONCLUSION: This analysis demonstrates a positive association between BMI
      and the presence of EE, especially in males. The risk seems to progressively
      increase with increasing weight.

PMID- 22654455
TI  - Prevalence of depressive and anxiety disorders in Chinese gastroenterological
      outpatients.
AB  - AIM: To investigate the prevalence and physicians' detection rate of depressive
      and anxiety disorders in gastrointestinal (GI) outpatients across China. METHODS:
      A hospital-based cross-sectional survey was conducted in the GI outpatient
      departments of 13 general hospitals. A total of 1995 GI outpatients were
      recruited and screened with the Hospital Anxiety and Depression Scale (HADS). The
      physicians of the GI departments performed routine clinical diagnosis and
      management without knowing the HADS score results. Subjects with HADS scores >= 8
      were subsequently interviewed by psychiatrists using the Mini International
      Neuropsychiatric Interview (MINI) to make further diagnoses. RESULTS: There were
      1059 patients with HADS score >= 8 and 674 (63.64%) of them undertook the MINI
      interview by psychiatrists. Based on the criteria of Diagnostic and Statistical
      Manual of Mental Disorders (4th edition), the adjusted current prevalence for
      depressive disorders, anxiety disorders, and comorbidity of both disorders in the
      GI outpatients was 14.39%, 9.42% and 4.66%, respectively. Prevalence of
      depressive disorders with suicidal problems [suicide attempt or suicide-related
      ideation prior or current; module C (suicide) of MINI score >= 1] was 5.84% in
      women and 1.64% in men. The GI physicians' detection rate of depressive and
      anxiety disorders accounted for 4.14%. CONCLUSION: While the prevalence of
      depressive and anxiety disorders is high in Chinese GI outpatients, the detection
      rate of depressive and anxiety disorders by physicians is low.

PMID- 22654456
TI  - Evaluation of malignancy using Ki-67, p53, EGFR and COX-2 expressions in
      gastrointestinal stromal tumors.
AB  - AIM: To investigate the role of expressions of Ki-67, p53, epidermal growth
      factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in gastrointestinal stromal
      tumor (GIST) grading and prognosis. METHODS: Tumor tissue was collected
      retrospectively from 96 patients with GIST. Antibodies against Ki-67, p53, EGFR
      and COX-2 were used for immunohistochemical staining. Tumor grading was
      designated according to a consensus system and the staining was quantified in 3
      categories for each antibody in the statistical analysis. RESULTS: The Ki-67
      expression in GISTs was significantly associated with the size of the tumors,
      mitotic rate and the risk of malignancy (chi(2) = 15.51, P = 0.02; chi(2) =
      22.27, P < 0.001; chi(2) = 20.05; P < 0.001). The p53 expression was also
      significantly correlated with mitotic rate and the risk of malignancy (chi(2) =
      9.92, P = 0.04; chi(2) = 9.97; P = 0.04). Over-expression of Ki-67 was strongly
      correlated with poor survival (chi(2) = 10.44, P = 0.006), but no correlation was
      found between the expression of p53, EGFR or COX-2 and survival. Multivariate
      analysis further demonstrated that Ki-67 expression (relative risk = 15.78, 95%
      CI: 4.25-59.37) could be used as an independent prognostic value for GIST
      patients. Adjuvant imatinib therapy could improve clinical outcomes in the
      patients with high risk and intermediate risk of recurrence after complete tumor
      resections (median survival time: 52 mo vs 37 mo, chi(2) = 7.618, P = 0.006).
      CONCLUSION: Our results indicated that the expression of Ki-67 could be used as
      an independent prognostic factor for GIST patients.

PMID- 22654457
TI  - Effects of glycine on phagocytosis and secretion by Kupffer cells in vitro.
AB  - AIM: To investigate the effects and mechanisms of action of glycine on
      phagocytosis and tumor necrosis factor (TNF)-alpha secretion by Kupffer cells in
      vitro. METHODS: Kupffer cells were isolated from normal rats by collagenase
      digestion and Percoll density gradient differential centrifugation. After culture
      for 24 h, Kupffer cells were incubated in fresh Dulbecco's Modification of
      Eagle's Medium containing glycine (G1: 1 mmol/L, G2: 10 mmol/L, G3: 100 mmol/L
      and G4: 300 mmol/L) for 3 h, then used to measure phagocytosis by a bead test,
      TNF-alpha secretion after lipopolysaccharide stimulation by radioactive
      immunoassay, and microfilament and microtubule expression by staining with
      phalloidin-fluorescein isothiocyanate (FITC) or a monoclonal anti-alpha tubulin
      FITC antibody, respectively, and evaluated under a ultraviolet fluorescence
      microscope. RESULTS: Glycine decreased the phagocytosis of Kupffer cells at both
      30 min and 60 min (P < 0.01, P < 0.05). The numbers of beads phagocytosed by
      Kupffer cells in 30 min were 16.9 +/- 4.0 (control), 9.6 +/- 4.1 (G1), 12.1 +/-
      5.7 (G2), 8.1 +/- 3.2 (G3) and 7.5 +/- 2.0 (G4), and were 22.5 +/- 7.9 (control),
      20.1 +/- 5.8 (G1), 19.3 +/- 4.8 (G2), 13.5 +/- 4.7 (G3) and 9.2 +/- 3.1 (G4)
      after 60 min. TNF-alpha secretion by Kupffer cells in G1 (0.19 +/- 0.03), G2
      (0.16 +/- 0.04), G3 (0.14 +/- 0.03) and G4 (0.13 +/- 0.05) was significantly less
      than that in controls (0.26 +/- 0.03, P < 0.01), and the decrease in secretion
      was dose-dependent (P < 0.05). Microfilaments of Kupffer cells in G2, G3 and G4
      groups were arranged in a disorderly manner. The fluorescence densities of
      microtubules in G1 (53.4 +/- 10.5), G2 (54.1 +/- 14.6), G3 (64.9 +/- 12.1) and G4
      (52.1 +/- 14.2) were all lower than those in the controls (102.2 +/- 23.7, P <
      0.01), but the decrease in microtubule fluorescence density was not dose
      dependant. CONCLUSION: Glycine can decrease the phagocytosis and secretion by
      Kupffer cells in vitro, which may be related to the changes in the expression of
      microfilaments and microtubules induced by Kupffer cells.

PMID- 22654458
TI  - Exceptionally rare cause of a total stomach resection.
AB  - The first-ever case of a 54-year-old woman who overdosed on non-steroidal anti
      inflammatory drugs in an attempt at suicide. Before that incident, she had not
      been treated for coexisting diseases such as rheumatoid arthritis or depression.
      At the time of admission to the General Surgery Department, the patient reported
      pains in the epigastric region with accompanying nausea and vomiting with mucous
      content as well as the inability to ingest food orally. Despite parenteral and
      enteral feeding, the patient exhibited a drop in body mass. The histopathologic
      examination of a sample taken from the stomach during gastroscopy showed some non
      specific necrotic and inflammatory masses with granulation. Intraoperatively, a
      very small, infiltrated stomach with an initial section of duodenum was
      identified. A total stomach resection together with the reconstruction of
      digestive tract continuity was performed using the Roux-Y method. Histopathologic
      examination of the stomach revealed a deep, chronic and exacerbated inflammatory
      condition with an extensive ulceration over the entire length of the stomach,
      reaching up to the pylorus. Additionally, numerous lymphatic glands with
      inflammatory reaction changes were observed.

PMID- 22654460
TI  - Welcoming nora: a family event.
AB  - In this column, Allison and Paul Walsh share the story of the birth of Nora,
      their third baby and their second child to be born at home. Allison and Paul
      share their individual memories of labor and birth. But their story is only part
      of the story of Nora's birth. Nora's birth was a family event, with Allison and
      Paul's other children very much part of the experience. Jane and Gavin share
      their own memories of their baby sister's birth.

PMID- 22654459
TI  - Lamivudine treatment enabling right hepatectomy for hepatocellular carcinoma in
      decompensated cirrhosis.
AB  - A 69-year-old man was admitted to our hospital in October 2003, for further
      examination of two liver tumors. He was diagnosed with hepatocellular carcinoma
      (HCC) arising from decompensated hepatitis B virus (HBV)-related cirrhosis. Long
      term lamivudine administration improved liver function dramatically despite
      repeated treatment for HCC. His Child-Pugh score was 9 points at start of
      lamivudine treatment, improving to 5 points after 1 year. His indocyanine green
      at 15 min after injection test score was 48% before lamivudine treatment,
      improving to 22% after 2 years and to 5% after 4 years. Radiofrequency ablation
      controlled the HCC foci and maintained his liver function. In April 2009,
      abdominal computed tomography revealed a tumor thrombus in the right portal vein.
      Since his indocyanine green test results had improved to less than 10%, we
      performed a right hepatectomy, which was successful. To our knowledge, there have
      been no documented reports of patients undergoing successful right hepatectomy
      for HCC arising from decompensated cirrhosis. The findings observed in our
      patient indicate the importance of nucleoside analogs for treating HBV-related
      HCC.

PMID- 22654461
TI  - A road map for change: ensuring that women have breastfeeding support.
AB  - Despite new policy changes and national dialogue about breastfeeding, significant
      barriers in all sectors of society continue to exist for most women who decide to
      breastfeed. Breastfeeding rates fall short of current medical recommendations and
      our nation's own public health goals, resulting in significant health and
      economic impacts. The launch of The Surgeon General's Call to Action to Support
      Breastfeeding provides an opportunity for a society-wide approach in removing
      barriers that make it difficult for many women to succeed. Childbirth educators
      are urged to use these action steps as a springboard to influence lasting change
      so that all women have the opportunity to breastfeed their children.

PMID- 22654462
TI  - The value of listening to grandmothers' infant-feeding stories.
AB  - The purpose of this study was to examine the usefulness of storytelling as a
      foundation for communicating with grandmothers about breastfeeding. The benefits
      of storytelling are applied to an analysis of infant-feeding stories that
      grandmothers told during a focus group study conducted by the authors. Thirty
      five grandmothers participated in the study. A qualitative content analysis of
      the interview transcripts revealed that grandmothers' infant-feeding stories
      provided insights into the people (characters) and circumstances (setting) that
      affected their early experiences of infant feeding. By asking grandmothers to
      tell their stories, health-care professionals may understand the personal and
      cultural context grandmothers bring to their support of new mothers and
      facilitate a place for grandmothers' voices to be heard.

PMID- 22654463
TI  - The evidence base for the cues program for mothers of very low birth weight
      infants: an innovative approach to reduce anxiety and support sensitive
      interaction.
AB  - Very low birth weight (VLBW) infants, born weighing less than 1,500 g, are at
      risk for several developmental problems. Consequently, there has been interest in
      developing intervention programs to prevent such problems. This article describes
      the empirical evidence that guided the development of an innovative,
      multicomponent intervention program for mothers of VLBW infants, as well as the
      program content and features. Based on the evidence, the program was designed to
      include six sessions and commence shortly after birth to reduce maternal
      psychological distress during the infant's hospitalization in the neonatal
      intensive care unit and to promote sensitive mother-infant interaction. The
      program incorporates various learning activities, including written materials,
      observational exercises, discussion, and video feedback.

PMID- 22654464
TI  - Fathers online: learning about fatherhood through the internet.
AB  - In the transition to fatherhood, men face numerous challenges. Opportunities to
      learn new practices and gain support are limited, although the provisions of
      father-specific spaces such as fathers' antenatal classes or "responsible
      fathering" programs are important advances. This article explores how men use the
      social space of a father-specific Internet chat room to learn about fathering.
      Messages to an Australian-hosted, father-specific chat room (for fathers of
      infants or young children) were examined, and three overlapping themes
      illustrated men's perceptions of their transition to fatherhood. The themes
      concerned recognition of and response to a lack of social space, services, and
      support for new fathers. The implications for fathers' perinatal education are
      discussed.

PMID- 22654465
TI  - Teaching in a patient-centered medical home.
AB  - Teaching Lamaze International classes in a patient-centered medical home allows
      the childbirth educator the best environment for giving evidence-based
      information and empowering parents to give birth their way. Patient-centered
      medical home facilities and providers practice evidence-based care and adhere to
      the principles of family-centered maternity care. In patient-centered medical
      homes, women can expect to give birth using the Lamaze Healthy Birth Practices
      and to fully participate in their care with appropriate interventions and the
      right to informed consent and informed refusal.

PMID- 22654466
TI  - Pain, suffering, and trauma in labor and prevention of subsequent posttraumatic
      stress disorder.
AB  - In this column, Kimmelin Hull, community manager of Science & Sensibility, Lamaze
      International's research blog, reprints and discusses a recent blog post series
      by acclaimed writer, lecturer, doula, and normal birth advocate Penny Simkin.
      Examined here is the fruitful dialog that ensued-including testimonies from blog
      readers about their own experiences with traumatic birth and subsequent
      posttraumatic stress disorder. Hull further highlights the impact traumatic birth
      has not only on the birthing woman but also on the labor team-including doulas
      and childbirth educators-and the implied need for debriefing processes for birth
      workers. Succinct tools for assessing a laboring woman's experience of pain
      versus suffering are offered by Simkin, along with Hull's added suggestions for
      application during the labor and birth process.

PMID- 22654467
TI  - Vitamin d: popular cardiovascular supplement but benefit must be evaluated.
AB  - Vitamin D deficiency is prevalent in the United States. Understanding any
      relationship between this deficiency and cardiovascular disease is essential.
      Vitamin D, as used, refers to both D(2) and D(3); both are present in over-the
      counter supplements, whereas D(2) is the prescription product in the United
      States. In the liver, both D(2) and D(3) are converted to 25-hydroxyvitamin D,
      the major circulating metabolite that is measured to assess activity. The actual
      active form at a cellular level is 1,25-dihydroxyvitamin D; however, it does not
      correlate well with overall activity. Estimated vitamin D deficiency is, at
      times, more than 50%. Despite absence of placebo-controlled randomized trials,
      much information associates vitamin D deficiency with cardiovascular risk and
      supports benefit from vitamin D supplementation. There are also reports that
      explain how this benefit from vitamin D may occur. Vitamin D appears to cause
      only minimal changes in low- and high-density lipoprotein levels. Therefore, any
      cardiovascular benefit that may exist from vitamin D probably has an explanation
      other than an effect on levels of these lipoproteins. There is more association
      of vitamin D deficiency with metabolic syndrome components such as an increase in
      blood pressure, elevated plasma triglycerides, and impaired insulin metabolism.
      Possible documentation of cardiovascular benefit from vitamin D includes some
      evidence for endothelial stabilization and decreased inflammation in arteries. If
      the clinician decides that recommendation of vitamin D supplementation is
      warranted, it is reassuring that toxicity is rare. Furthermore, this toxicity
      involves doses exceeding those of most clinical trials and mainly has involved
      hypercalcemia. Vitamin D supplementation is easy and can be taken as a dose of
      2000 IU daily on an indefinite basis. In 1997, the Food and Nutrition Board of
      the U.S. Institute of Medicine considered this the safe tolerable upper limit,
      but this is not based on current evidence. Some practitioners, especially
      endocrinologists, recommend vitamin D at a dose of 50,000 IU per week for 8
      weeks, repeated if necessary to achieve a normal level of vitamin D. It appears
      appropriate to assess low vitamin D as a possible cardiovascular risk factor, but
      potential benefit of supplementation must be weighed against the current absence
      of definitive outcomes studies.

PMID- 22654468
TI  - Current status of lymphatic reconstructive surgery for chronic lymphedema: it is
      still an uphill battle!
AB  - The goal of reconstructive lymphatic surgery is to restore normal lymphatic
      function to "cure" permanently the lymphedematous limb in patients with
      lymphedema. In reality, reconstructive surgery remains an adjunctive treatment at
      best, with its current indication being refractory lymphedema in patients treated
      with complex decongestive therapy (CDT) alone. The role of reconstructive
      lymphatic surgery remains controversial and is far from being accepted as
      standard independent therapy because of multiple reasons. However, reconstructive
      surgery appears to be most effective in controlling the progression of lymphedema
      during the early stages when the paralyzed lymph vessels are still able to
      function and recover. Our experience in reconstructive surgery has shown that
      improved long-term results are dependent on prolonged patient compliance with
      maintenance CDT and the prevention and treatment of infection. To better
      understand the role of reconstructive surgery in the management of chronic
      lymphedema, well-constructed clinical trials based on well-organized multicenter
      studies with similar protocols are mandated. For the future, it remains the only
      possible treatment method capable of providing a cure.

PMID- 22654469
TI  - Effect of body mass index on postoperative transfusions and 24-hour chest-tube
      output.
AB  - An increasing obese population in the United States focuses attention on the
      effect of obesity on surgical outcomes. Our objective was to see if obesity,
      determined by body mass index (BMI), contributed to bleeding in coronary artery
      bypass graft (CABG) surgery as measured by intraoperative and postoperative
      packed red blood cell transfusion frequency and amount and 24-hour chest-tube
      output. A retrospective chart review examined 150 subjects undergoing single
      surgeon off-pump or on-pump CABG surgery between September 2006 and April 2009.
      BMI groups included normal-weight (BMI <25), overweight (BMI 25 to 29), and obese
      (BMI >=30). Analyses used a chi-square test to determine variances in number of
      transfusions, and ANOVA for transfusion amount and 24-hour chest-tube amount. The
      percentage of subjects receiving intraoperative transfusions varied significantly
      by BMI group (p = 0.022). The percentage of subjects receiving transfusions in
      the 72-hour postoperative period showed a decreasing linear trend based on BMI
      group (p = 0.054). The percentage of subjects receiving transfusions in the
      combined intraoperative or 72-hour postoperative period showed a decreasing
      linear trend based on BMI group (p = 0.054). The transfusion amount during the 72
      hour postoperative period varied significantly between BMI groups (p = 0.021),
      and the test for a linear decrease across groups was significant (p = 0.020).
      Twenty-four hour chest-tube output showed variation across all three BMI
      categories (p = 0.018) with chest-tube output decreasing with increasing obesity
      in a linear fashion (p = 0.006). Transfusion rate and amount indicate total blood
      loss is decreased in the obese, and chest-tube output findings give a direct
      measurable indicator of blood loss from the surgical site indicating increasing
      BMI is linearly correlated with decreasing postoperative bleeding.

PMID- 22654470
TI  - A cohort study to analyze the risk of venous thromboembolism mortality in
      patients admitted to the general medicine department, tan tock seng hospital,
      singapore.
AB  - The purpose of this study was to assess the risk of venous thromboembolism (VTE)
      in patients admitted to the Tan Tock Seng Hospital (TTSH), Singapore during
      October and November 2009. The primary outcome assessed was mortality due to VTE,
      or development of deep vein thrombosis or pulmonary embolism (PE) within 3 months
      from the day of admission. Both univariate and multivariate analyses were
      performed for all-cause mortality and deaths associated with PE. Seven hundred
      twenty-one patients admitted to the 5th floor of the General Medicine Department,
      TTSH, during the 2 months were analyzed. There were 368 (51.04%) female patients
      and 353 (48.96%) male patients. As per race distribution, 566 (78.50%) patients
      were Chinese, 100 (13.86%) patients were Malaysians, 46 (6.38%) patients were
      Indians, and 9 (1.26%) were other races. Four hundred ninety-two (68.24%) were
      independent for activities of daily living (ADL) and 229 (31.76%) were dependent
      for all ADL. There were in all 42 deaths. There were definite PE deaths in 2
      (4.76%) patients, probable PE deaths in 3 (7.14%) patients, and suspected PE
      deaths in 8 (19.05%) patients. Twenty (47.62%) deaths were due to pneumonia, 3
      (7.14%) deaths were due to urinary tract infections, and 4 (9.52%) deaths were
      due to other infections. Two (4.76%) deaths were due to myocardial infarction.
      The risk of VTE was high in acutely ill patients admitted to the General Medicine
      Department, TTSH, Singapore. The factors that predispose patients to a very high
      risk are ADL dependence, acute heart failure, past history of VTE, or if they are
      clinically dehydrated and have acute renal failure. This warrants increased
      awareness and need for VTE prophylaxis.

PMID- 22654471
TI  - Predictors of provisional stenting in patients undergoing lower extremity
      arterial interventions.
AB  - Predictors of provisional stenting in patients undergoing lower extremity
      arterial interventions remain unclear. We performed an ad hoc analysis on the
      predictors of provisional stenting during infrainguinal arterial percutaneous
      interventions using data from the Percutaneous Lower Extremity Arterial
      Interventions Using Primary Balloon Angioplasty versus Silverhawk Atherectomy
      (SA) and Adjunctive Balloon Angioplasty trial. In the above trial, SA of
      infrainguinal de novo arterial lesions was shown to reduce significantly
      provisional stenting compared with primary percutaneous transluminal angioplasty
      (PTA). In this ad hoc analysis, patients were divided into two groups based on
      whether provisional stenting has occurred. Univariate analysis was conducted
      between the stent versus the no-stent group. Logistic regression (LR) analysis
      was performed to model for the predictors of provisional stenting. Variables
      included were diabetes, presence of moderate calcification (versus none to
      little), age, gender, hypercholesterolemia, Transatlantic Intersociety Consensus
      (TASC) D lesion (vs. TASC A to C), and treatment method (primary PTA vs. SA with
      adjunctive PTA). By LR analysis, predictors of stenting were as follows: moderate
      calcification (odds ratio [OR] 6.56, 95% confidence interval [CI] 1.21 to 35.56,
      p = 0.029), primary PTA (vs. SA) (OR 0.19, 95% CI 0.04 to 0.93, p = 0.04), and
      TASC D lesions (vs. A to C) (OR 0.10, 95% CI 0.01 to 0.87, p = 0.037).
      Provisional stenting in infrainguinal interventions is predicted by the use of
      primary PTA, presence of moderate calcification, and TASC D lesions after
      controlling for gender, age, hypercholesterolemia, and diabetes.

PMID- 22654472
TI  - Twin circumflex arteries with left sinus of valsalva origin: a case report.
AB  - Coronary artery anomalies are not uncommon. The importance of coronary anomalies
      varies from unimportant to life threatening. Herein, we report for the first time
      twin circumflex coronary arteries originating separately from the left sinus of
      Valsalva.

PMID- 22654473
TI  - Acute Myocardial Infarction with Severe ST Segment Elevation Treated with
      Percutaneous Coronary Intervention More than Two Days after Onset: A Case with
      Remarkable Recovery.
AB  - The patient was a 65-year-old man with marked ST-elevation myocardial infarction.
      Cardiac catheterization revealed an occluded middle portion of the left anterior
      descending artery and no collateral circulation. Percutaneous coronary
      intervention (PCI) was performed, and ST elevation improved 5 days after PCI.
      Almost all electrocardiogram (ECG) findings were normal 6 months later.
      Echocardiographic findings were also normal. This case was very successful and
      unusual in that no ventricular aneurysm formed despite ST elevation continuing
      for a few days and that ECG and left ventricular function were nearly normal
      after PCI performed days after the onset in a case without collateral
      circulation.

PMID- 22654474
TI  - Left ventricular pseudoaneurysm complicating inferior myocardial infarction: a
      case report.
AB  - Acquired pseudoaneurysm of the left ventricle is a very rare disorder and mostly
      occurs after large transmural myocardial infarction (MI) with peak creatine
      phosphokinase-MB levels greater than 150 IU/mL. Patients developing left
      ventricular (LV) pseudoaneurysm usually present with angina or heart failure
      symptoms. Although different imaging modalities exist, coronary angiography is
      the gold standard for diagnosis. Surgery is the treatment of choice for LV
      pseudoaneurysms detected in the first months after MI. Here we report the case of
      a 74-year-old woman who presented with a relatively small inferior MI due to
      right coronary artery occlusion and complicated by LV pseudoaneurysm.

PMID- 22654475
TI  - Percutaneous mechanical thrombectomy and pharmacologic thrombolysis for renal
      artery embolism: case report and review of endovascular treatment.
AB  - Renal artery embolism (RAE) is an uncommon event that is associated with a high
      rate of renal loss. We present a case of RAE to a solitary kidney that was
      treated with combined percutaneous rheolytic thrombectomy, intra-arterial
      thrombolysis, and supplemental renal artery stent placement.

PMID- 22654476
TI  - Long-term positive remodeling of the right coronary artery after reimplantation
      from the pulmonary artery to the ascending aorta.
AB  - A 53-year-old woman, nonsmoking patient, with a history of surgically corrected
      anomalous origin of the right coronary artery from the pulmonary artery 17 years
      prior to admission, presented to our department complaining of mild, left-sided
      exertional chest pain for the past 3 months. She underwent a computed tomography
      examination of the heart and coronary angiography revealing postsurgical changes
      to the coronary vasculature and severe stenosis of the left circumflex artery,
      which was successfully treated by percutaneous stent implantation.

PMID- 22654477
TI  - Dynamics within surfactant monolayers.

PMID- 22654478
TI  - Structural and Spectral Analyses of 2-[(2-Benzothiazolylmethyl)thio]-benzenamine
      and 2-[(2-Benzothiazolylmethyl)thio]-benzenamine hydrobromide.
AB  - 2-[2-benzothiazoylmethyl)thio]-benzenamine, which was first reported in 1898, was
      isolated from the reaction of bromoacetyl bromide and 2-aminothiophenol [1]. The
      product crystallized from an aqueous methanol solution of the reaction mixture to
      which nickel(II) acetate had been added. 2-[(2-benzothiazolylmethyl)thio]
      benzenamine crystallized in the monoclinic system, in space group C2/c, with cell
      dimensions of a = 27.392 (19) A, b = 4.730 (3) A, and c = 23.686 (16) A, beta =
      122.465 (6) degrees , V = 2589(3) A(3), Z = 8 and refined to R = 0.0343 and R(w)
      = 0.0844. Crystallization from methanol yielded the product as the hydrobromide
      salt in the monoclinic space group Cc, with cell dimensions of a = 10.488 (3) A,
      b = 33.404 (9) A, c = 5.2578 (14) A, beta = 116.769(2) degrees , V = 1644.7(8)
      A(3), Z = 4 and refined to R = 0.0296 and R(w) = 0.0600. Mass spectral and NMR
      analyses confirmed that the bulk and crystalline compound were all 2-[(2
      benzothiazolylmethyl)thio]-benzenamine.

PMID- 22654479
TI  - Commercial dengue rapid diagnostic tests for point-of-care application: recent
      evaluations and future needs?
AB  - Dengue fever, dengue haemorrhagic fever, and dengue shock syndrome (DF/DHF/DSS)
      are tropical diseases that cause significant humanitarian and economic hardship.
      It is estimated that more than 2.5 billion people are at risk of infection and
      more than 100 countries have endemic dengue virus transmission. Laboratory tests
      are essential to provide an accurate diagnosis of dengue virus infection so that
      appropriate treatment and patient management may be administered. In many dengue
      endemic settings, laboratory diagnostic resources are limited and simple rapid
      diagnostic tests (RDTs) provide opportunities for point-of-care diagnosis. This
      paper addresses current issues relating to the application of commercial dengue
      RDTs for the diagnosis of acute dengue virus infection, recent diagnostic
      evaluations, and identifies future needs.

PMID- 22654480
TI  - Effect of marine omega 3 fatty acids on methylmercury-induced toxicity in fish
      and mammalian cells in vitro.
AB  - Methylmercury (MeHg) is a ubiquitous environmental contaminant which
      bioaccumulates in marine biota. Fish constitute an important part of a balanced
      human diet contributing with health beneficial nutrients but may also contain
      contaminants such as MeHg. Interactions between the marine n-3 fatty acids
      eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) with
      MeHg-induced toxicity were investigated. Different toxic and metabolic responses
      were studied in Atlantic salmon kidney (ASK) cell line and the mammalian kidney
      derived HEK293 cell line. Both cell lines were preincubated with DHA or EPA prior
      to MeHg-exposure, and cell toxicity was assessed differently in the cell lines by
      MeHg-uptake in cells (ASK and HEK293), proliferation (HEK293 and ASK), apoptosis
      (ASK), oxidation of the red-ox probe roGFP (HEK293), and regulation of selected
      toxicological and metabolic transcriptional markers (ASK). DHA was observed to
      decrease the uptake of MeHg in HEK293, but not in ASK cells. DHA also increased,
      while EPA decreased, MeHg-induced apoptosis in ASK. MeHg exposure induced changes
      in selected metabolic and known MeHg biomarkers in ASK cells. Both DHA and MeHg,
      but not EPA, oxidized roGFP in HEK293 cells. In conclusion, marine n-3 fatty
      acids may ameliorate MeHg toxicity, either by decreasing apoptosis (EPA) or by
      reducing MeHg uptake (DHA). However, DHA can also augment MeHg toxicity by
      increasing oxidative stress and apoptosis when combined with MeHg.

PMID- 22654482
TI  - Camel milk triggers apoptotic signaling pathways in human hepatoma HepG2 and
      breast cancer MCF7 cell lines through transcriptional mechanism.
AB  - Few published studies have reported the use of crude camel milk in the treatment
      of stomach infections, tuberculosis and cancer. Yet, little research was
      conducted on the effect of camel milk on the apoptosis and oxidative stress
      associated with human cancer. The present study investigated the effect and the
      underlying mechanisms of camel milk on the proliferation of human cancer cells
      using an in vitro model of human hepatoma (HepG2) and human breast (MCF7) cancer
      cells. Our results showed that camel milk, but not bovine milk, significantly
      inhibited HepG2 and MCF7 cells proliferation through the activation of caspase-3
      mRNA and activity levels, and the induction of death receptors in both cell
      lines. In addition, Camel milk enhanced the expression of oxidative stress
      markers, heme oxygenase-1 and reactive oxygen species production in both cells.
      Mechanistically, the increase in caspase-3 mRNA levels by camel milk was
      completely blocked by the transcriptional inhibitor, actinomycin D; implying that
      camel milk increased de novo RNA synthesis. Furthermore, Inhibition of the
      mitogen activated protein kinases differentially modulated the camel milk-induced
      caspase-3 mRNA levels. Taken together, camel milk inhibited HepG2 and MCF7 cells
      survival and proliferation through the activation of both the extrinsic and
      intrinsic apoptotic pathways.

PMID- 22654483
TI  - Influence of skin diseases on fingerprint recognition.
AB  - There are many people who suffer from some of the skin diseases. These diseases
      have a strong influence on the process of fingerprint recognition. People with
      fingerprint diseases are unable to use fingerprint scanners, which is
      discriminating for them, since they are not allowed to use their fingerprints for
      the authentication purposes. First in this paper the various diseases, which
      might influence functionality of the fingerprint-based systems, are introduced,
      mainly from the medical point of view. This overview is followed by some examples
      of diseased finger fingerprints, acquired both from dactyloscopic card and
      electronic sensors. At the end of this paper the proposed fingerprint image
      enhancement algorithm is described.

PMID- 22654481
TI  - Metabolic engineering of yeast and plants for the production of the biologically
      active hydroxystilbene, resveratrol.
AB  - Resveratrol, a stilbenic compound deriving from the phenyalanine/polymalonate
      route, being stilbene synthase the last and key enzyme of this pathway, recently
      has become the focus of a number of studies in medicine and plant physiology.
      Increased demand for this molecule for nutraceutical, cosmetic and possibly
      pharmaceutic uses, makes its production a necessity. In this context, the use of
      biotechnology through recombinant microorganisms and plants is particularly
      promising. Interesting results can indeed arise from the potential of genetically
      modified microorganisms as an alternative mechanism for producing resveratrol.
      Strategies used to tailoring yeast as they do not possess the genes that encode
      for the resveratrol pathway, will be described. On the other hand, most interest
      has centered in recent years, on STS gene transfer experiments from various
      origins to the genome of numerous plants. This work also presents a comprehensive
      review on plant molecular engineering with the STS gene, resulting in disease
      resistance against microorganisms and the enhancement of the antioxidant
      activities of several fruits in transgenic lines.

PMID- 22654486
TI  - Impact of the partitioning scheme on divergence times inferred from Mammalian
      genomic data sets.
AB  - Data partitioning has long been regarded as an important parameter for
      phylogenetic inference. The division of heterogeneous multigene data sets into
      partitions with similar substitution patterns is known to increase the
      performance of probabilistic phylogenetic methods. However, the effect of the
      partitioning scheme on divergence time estimates has generally been ignored. To
      investigate the impact of data partitioning on the estimation of divergence
      times, we have constructed two genomic data sets. The first one with 15 nuclear
      genes comprising 50,928 bp were selected from the OrthoMam database; the second
      set was composed of complete mitochondrial genomes. We studied two partitioning
      schemes: concatenated supermatrices and partitioned gene analysis. We have also
      measured the impact of taxonomic sampling on the estimates. After drawing
      divergence time inferences using the uncorrelated relaxed clock in BEAST, we have
      compared the age estimates between the partitioning schemes. Our results show
      that, in general, both schemes resulted in similar chronological estimates,
      however the concatenated data sets were more efficient than the partitioned ones
      in attaining suitable effective sample sizes.

PMID- 22654484
TI  - Inference of tumor phylogenies from genomic assays on heterogeneous samples.
AB  - Tumorigenesis can in principle result from many combinations of mutations, but
      only a few roughly equivalent sequences of mutations, or "progression pathways,"
      seem to account for most human tumors. Phylogenetics provides a promising way to
      identify common progression pathways and markers of those pathways. This
      approach, however, can be confounded by the high heterogeneity within and between
      tumors, which makes it difficult to identify conserved progression stages or
      organize them into robust progression pathways. To tackle this problem, we
      previously developed methods for inferring progression stages from heterogeneous
      tumor profiles through computational unmixing. In this paper, we develop a novel
      pipeline for building trees of tumor evolution from the unmixed tumor data. The
      pipeline implements a statistical approach for identifying robust progression
      markers from unmixed tumor data and calling those markers in inferred cell
      states. The result is a set of phylogenetic characters and their assignments in
      progression states to which we apply maximum parsimony phylogenetic inference to
      infer tumor progression pathways. We demonstrate the full pipeline on simulated
      and real comparative genomic hybridization (CGH) data, validating its
      effectiveness and making novel predictions of major progression pathways and
      ancestral cell states in breast cancers.

PMID- 22654487
TI  - Mitochondrial Genetic Differentiation of Spirlin (Actinopterigii: Cyprinidae) in
      the South Caspian Sea basin of Iran.
AB  - BACKGROUND: Knowledge about Alburnoides remains lacking relative to many other
      species, resulting in a lack of a systematic position and taxonomic diagnosis.
      Basic biological information for Alburnoides has been constructed, and it is
      necessary to understand further and obtain more information about this species.
      Its phylogenetic relationships are still debated and no molecular data have been
      used to study this taxon in Iran. A holistic approach for genetic methods was
      adopted to analyze possible spirlin population differences at selected centers in
      the south Caspian Sea basin of Iran. METHODS: The phylogenetic relationships were
      determined based on 774 base pairs of the mitochondrial cytochrome b gene of 32
      specimens of spirlin from nine locations in the south Caspian Sea drainage basin
      of Iran. The nucleotide sequences were subjected to phylogenetic analysis using
      the neighbor-joining, maximum parsimony, maximum likelihood, and Bayesian
      methods. RESULTS: The mitochondrial gene tree largely supports the existence of
      three major clades. The western populations (clade I) may be considered as
      Alburnoides eichwaldii, whereas the Talar river populations (clade II) are
      represented as Alburnoides sp.1 and the eastern populations (clade III) may be
      distinct taxa of Alburnoides sp.2. CONCLUSION: This molecular evidence supports
      the hypothesis that A. bipunctatus does not exist in the south Caspian Sea basin
      of Iran, and that the western and eastern populations are distinct taxa.

PMID- 22654488
TI  - Two chromatographic methods for the determination of some antimigraine drugs.
AB  - Two stability indicating chromatographic methods were proposed for the
      determination of almotriptan, eletriptan, and rizatriptan, in presence of their
      acid degradation products. The first method is a quantitative densitometric thin
      layer chromatography. The developing systems were; acetonitrile: methanol:
      dichloromethane: ammonia (10:6:3:1 v/v), ethyl acetate: methanol: ammonia (15:4:1
      v/v), and methanol: acetonitrile: ammonia (9:4:1 v/v) for almotriptan, eletriptan
      and rizatriptan respectively. The TLC plates were scanned at 235 nm. Linear
      relationships were obtained over concentration ranges (5-50 MUg/spot) for
      almotriptan and rizatriptan, and (5-60 MUg/spot) for eletriptan. The second
      method based on the separation and determination of the studied drugs, using RP
      HPLC technique. The separation was achieved on C18 Hypersil column, elution was
      carried out using phosphate buffer pH 3: methanol: acetonitrile (2: 1:1 v/v) at
      flow rate 2 mL/min and UV detection at 235 nm. Linear relationships were obtained
      over concentration ranges (10-200 MUg/mL) for almotriptan and eletriptan, and (10
      180 MUg/mL) for rizatriptan. The chromatographic methods were successfully
      applied for the determination of each of the studied drugs in pure form, tablet
      form, and in laboratory prepared mixtures with their acid degradation products.

PMID- 22654485
TI  - Role of cytokines in systemic lupus erythematosus: recent progress from GWAS and
      sequencing.
AB  - Systemic lupus erythematosus (SLE) is a complex autoimmune disorder, known to
      have a strong genetic component. Concordance between monozygotic twins is
      approximately 30-40%, which is 8-20 times higher than that of dizygotic twins. In
      the last decade, genome-wide approaches to understanding SLE have yielded many
      candidate genes, which are important to understanding the pathophysiology of the
      disease and potential targets for pharmaceutical intervention. In this paper, we
      focus on the role of cytokines and examine how genome-wide association studies,
      copy number variation studies, and next-generation sequencing are being employed
      to understand the etiology of SLE. Prominent genes identified by these approaches
      include BLK, FCgammaR3B, and TREX1. Our goal is to present a brief overview of
      genomic approaches to SLE and to introduce some of the key discussion points
      pertinent to the field.

PMID- 22654489
TI  - Botulinum toxin injections for blepharospasm prior to ocular surgeries.
AB  - PURPOSE: The aim of this study was to show the efficiency of preoperative
      botulinum toxin A (Botox A) in patients with benign essential blepharospasm who
      were to undergo ocular surgery with local anesthesia. MATERIALS AND METHODS:
      Twenty-eight benign essential blepharospasm patients who were administered
      unilateral Botox A prior to ocular surgery between January 2004 and May 2011 were
      included in this study. Eleven cases had pterygiums, ten had cataracts, and four
      had glaucomas, while the remaining three had aphakia. All cases' severity of
      spasm (stage 0-4) and eyelid closing forces (stage 1-4) were evaluated according
      to the Jankovic scale prior to the injection, at 3 days, 14 days, 1 month, and 3
      months after Botox A injection. RESULTS: Of the patients enrolled in the study,
      16 were female and 12 were male, with an average age of 55.52 +/- 1.53 years (52
      65). Average onset of the Botox injection's effect was 2.8 +/- 0.9 (2-5) days.
      Its effect lingered for about 11.5 +/- 3.6 (8-22) weeks. The severity of spasm
      and eyelid closing forces of all the patients enrolled were compared prior to the
      injection at 3 and 14 days and the first and third months after the injection.
      There were statistically significant differences between prior to the injection
      and 3 days (P = 0.001), 14 days (P < 0.001) and 1 month after the injection (P <
      0.001). There was no statistically significant difference between prior to the
      injection and 3 months after the injection (P = 0.513). Fourteen days following
      the injection, the surgeries were successfully performed. CONCLUSION: Botox A
      administered prior to ocular surgery will control both blepharospasm and lower
      the risks that can be encountered before and during surgery, thus increasing the
      comfort of the patient and the surgeon.

PMID- 22654490
TI  - Case of acute optic nerve compression caused by tuberculum sellae meningioma with
      optic canal involvement.
AB  - We present detailed ophthalmic findings in a case of tuberculum sellae meningioma
      with acute visual symptoms due to optic canal involvement. A 62-year-old Japanese
      woman reported a 1-week history of headaches and blurred vision in her left eye.
      Her visual acuity was 0.3 in the left eye with no ophthalmoscopic abnormalities.
      A relative afferent pupillary defect and inferior temporal field defect were
      found in the left eye. Pattern visual evoked potentials were undetectable in the
      left eye. Enhanced magnetic resonance imaging showed a 9 mm intracranial lesion
      around the left optic nerve anterior to the chiasm. She was diagnosed with
      granulomatous inflammation because of the increased cell counts and protein
      concentration in the cerebrospinal fluid. She was treated with steroid pulse
      therapy, and her visual acuity and visual field defect improved to normal in 3
      weeks. However, 16 months after the onset, she suffered from headaches again and
      had a complete loss of vision in her left eye. There was no response to steroid
      pulse therapy. Enhanced magnetic resonance imaging revealed that the lesion had
      extended into the left optic canal, and emergency tumor removal surgery was
      carried out. The histopathological diagnosis was meningioma. One month after the
      surgery, her left visual acuity improved to 1.2, and her visual field was almost
      normal. Pattern visual evoked potentials were present but had a prolonged P(100)
      latency of 170 ms. A thinning of the ganglion cell complex was detected by
      optical coherence tomography. Ophthalmologists should be aware that a small
      tuberculum sellae meningioma can cause acute visual symptoms due to optic canal
      involvement. Early consultation with a neurosurgeon is necessary. Visual evoked
      potentials and optical coherence tomography are sensitive and helpful in
      following patients with optic nerve compression.

PMID- 22654491
TI  - The anterior segment of the eye in diabetes.
AB  - PURPOSE: A prospective study to examine the anterior segment of the eye in
      patients with diabetes mellitus. MATERIALS AND METHODS: The anterior segments of
      the eyes of 181 patients with diabetes mellitus were examined. The commonest
      finding in the lids was warts, followed by poliosis and chalazia, and, in the
      conjunctiva, tortuous conjunctival vessels inferiorly (36.50%), pterygium
      (14.92%), and pingueculum (14.37%). Corneal sensitivity was reduced in 25
      (13.80%) patients. Iris atrophy was the commonest finding in the iris. Dilatation
      of the pupil was delayed in 34 (18.79%) patients. Cataract was found in 119
      (65.75%) patients. Forty-one (22.65%) patients had intraocular pressure greater
      than 21 mmHg. Seven (3.87%) patients, four (2.21%) patients, and one (0.55%)
      patient had seventh, third, and fourth palsy, respectively. No patient had sixth
      nerve palsy. CONCLUSION: Primary care physicians and other allied health care
      professionals who are first in contact with patients are enjoined to familiarize
      themselves with the anterior segment features of diabetes mellitus and take
      necessary action when they are detected.

PMID- 22654492
TI  - Differential pharmacology and clinical utility of preservative-free tafluprost in
      the treatment of ocular hypertension and glaucoma.
AB  - Glaucoma is a chronic disease requiring lifelong treatment. Discomfort due to
      medications may affect patients' quality of life and may cause poor compliance,
      which leads to poor intraocular pressure control. To minimize the side effects of
      long-term treatment, preparations with lower benzalkonium chloride
      concentrations, preservative-free preparations and alternative preservatives have
      been developed and reported to have a lower rate of side effects. Tafluprost,
      launched on the ophthalmic market in 2008, is a new 16-phenoxy analogue of
      prostaglandin F(2alpha), clinically used as an ocular hypotensive agent for the
      treatment of glaucoma and ocular hypertension. The safety and intraocular
      pressure-lowering efficacy of tafluprost has been demonstrated in various
      preclinical and clinical studies.

PMID- 22654493
TI  - Retinal thickness after vitrectomy and internal limiting membrane peeling for
      macular hole and epiretinal membrane.
AB  - PURPOSE: To determine the retinal thickness (RT), after vitrectomy with internal
      limiting membrane (ILM) peeling, for an idiopathic macular hole (MH) or an
      epiretinal membrane (ERM). Also, to investigate the effect of a dissociated optic
      nerve fiber layer (DONFL) appearance on RT. METHODS: A non-randomized,
      retrospective chart review was performed for 159 patients who had successful
      closure of a MH, with (n = 148), or without (n = 11), ILM peeling. Also studied
      were 117 patients who had successful removal of an ERM, with (n = 104), or
      without (n = 13), ILM peeling. The RT of the nine Early Treatment Diabetic
      Retinopathy Study areas was measured by spectral domain optical coherence
      tomography (SD-OCT). In the MH-with-ILM peeling and ERM-with-ILM peeling groups,
      the RT of the operated eyes was compared to the corresponding areas of normal
      fellow eyes. The inner temporal/inner nasal ratio (TNR) was used to assess the
      effect of ILM peeling on RT. The effects of DONFL appearance on RT were evaluated
      in only the MH-with-ILM peeling group. RESULTS: In the MH-with-ILM peeling group,
      the central, inner nasal, and outer nasal areas of the retina of operated eyes
      were significantly thicker than the corresponding areas of normal fellow eyes. In
      addition, the inner temporal, outer temporal, and inner superior retina was
      significantly thinner than in the corresponding areas of normal fellow eyes.
      Similar findings were observed regardless of the presence of a DONFL appearance.
      In the ERM-with-ILM peeling group, the retina of operated eyes was significantly
      thicker in all areas, except the inner and outer temporal areas. In the MH-with
      ILM peeling group, the TNR was 0.86 in operated eyes, and 0.96 in fellow eyes (P
      < 0.001). In the ERM-with-ILM peeling group, the TNR was 0.84 in operated eyes,
      and 0.95 in fellow eyes (P < 0.001). TNR in operated eyes of the MH-without-ILM
      peeling group was 0.98, which was significantly greater than that of the MH-with
      ILM peeling group (P < 0.001). TNR in the operated eyes of the ERM-without-ILM
      peeling group was 0.98, which was significantly greater than that of ERM-with-ILM
      peeling group (P < 0.001). CONCLUSION: The thinning of the temporal retina and
      thickening of the nasal retina after ILM peeling does not appear to be disease
      specific. In addition, changes in RT after ILM peeling are not related to the
      presence of a DONFL appearance.

PMID- 22654494
TI  - Long-term outcomes of a pseudo 360-degree trabeculotomy ab externo technique for
      congenital glaucoma at children's medical center.
AB  - PURPOSE: To quantify the long-term outcomes of congenital glaucoma and surgical
      success rates following pseudo 360-degree trabeculotomy surgery at Children's
      Medical Center in Dallas. PATIENTS AND METHODS: An International Classification
      of Diseases (ICD-9) database was utilized for a retrospective chart review.
      Thirty-eight eyes of 24 who underwent primary trabeculotomy with a pseudo 360
      degree technique between June 1, 1992 and December 31, 2005 were studied.
      RESULTS: Mean age at the time of trabeculotomy was 11.1 +/- 3.0 months, with
      seven eyes operated on after 1 year of age. Mean follow-up was 85.1 +/- 9.0
      months. Mean intraocular pressure (IOP) at the time of glaucoma diagnosis was
      32.7 +/- 1.1 mmHg, and final mean IOP for all eyes (after trabeculotomy and any
      additional surgery and/or glaucoma medications) was 17.9 +/- 0.8 mmHg. With
      trabeculotomy and medication alone, mean final IOP was 19.9 +/- 1.1 mmHg, with a
      mean drop in IOP of 12.5 +/- 1.4 mmHg. Surgical success, defined by adequate IOP
      control, was achieved in 30 eyes (78.96%) at most recent follow-up. Kaplan-Meier
      analysis demonstrated 5- and 10-year survival probabilities of 93.1% and 66.8%,
      respectively. Seventeen eyes (44.7% of all eyes) achieved complete success,
      meaning IOP control <21 mmHg without additional medical therapy. All seventeen
      had primary congenital glaucoma (PCG); no eyes with aphakic glaucoma (AG) or
      Sturge-Weber syndrome (SWS) achieved complete success. Seven eyes (18.4%) failed
      primary trabeculotomy. Mean time to failure was 46.9 +/- 8.6 months. Eyes with
      SWS had a significantly higher failure rate (P = 0.009) and a 5.81 relative risk
      of failure (P = 0.026). CONCLUSIONS: Our long-term trabeculotomy success rates
      for congenital glaucoma compare favorably with existing reports in the
      literature. Eyes with AG and SWS may warrant consideration of alternative primary
      surgical methods, or closer postoperative surveillance.

PMID- 22654496
TI  - A survey of prosthetic eye wearers to investigate mucoid discharge.
AB  - BACKGROUND: This study aimed to better understand the causes and treatments of
      mucoid discharge associated with prosthetic eye wear by reviewing the literature
      and surveying anophthalmic patients. METHODS: An anonymous questionnaire was
      completed by 429 prosthetic eye wearers who used visual analog scales to self
      measure their discharge experience for four discharge characteristics: frequency,
      color, volume, and viscosity. These characteristics were analyzed with age,
      ethnicity, years wearing a prosthesis, eye loss cause, removal and cleaning
      regimes, hand-washing behavior, age of current prosthesis, and professional
      repolishing regimes as explanatory variables. Eighteen ocularists' Web sites
      containing comments on the cause and treatment of discharge were surveyed.
      RESULTS: Associations were found between discharge frequency and cleaning regimes
      with more frequent cleaning accompanying more frequent discharge. Color was
      associated with years of wearing and age, with more years of wearing and older
      people having less colored discharge. Volume was associated with cleaning regimes
      with more frequent cleaners having more volume. Viscosity was associated with
      cleaning regimes and years of wearing with more frequent cleaning and shorter
      wearing time accompanying more viscous discharge. No associations were found
      between discharge characteristics and ethnicity, eye loss cause, hand washing,
      age of current prosthesis, or repolishing regimes. Forty-seven percent of
      ocularists' Web sites advised that discharge was caused by surface deposits on
      the prosthesis, 29% by excessive handling of the prosthesis, and 24% by other
      causes. CONCLUSIONS: A standardized treatment protocol for managing discharge is
      lacking. More frequent prosthesis removal and cleaning was associated with more
      severe discharge, but the direction of cause and effect has not been established.
      Professional repolishing regimes had limited impact on discharge experience.
      Further research into the socket's response to prosthetic eye wear, including the
      physical, chemical, and biological elements of the conjunctiva, the socket
      fluids, and the deposits that cover the prosthetic eye is recommended.

PMID- 22654495
TI  - Efficacy and safety of travoprost 0.004%/timolol 0.5% fixed combination as
      transition therapy in patients previously on prostaglandin analog monotherapy.
AB  - PURPOSE: To assess the safety and efficacy of transitioning patients whose
      intraocular pressure (IOP) had been insufficiently controlled on prostaglandin
      analog (PGA) monotherapy to treatment with travoprost 0.004%/timolol 0.5% fixed
      combination with benzalkonium chloride (TTFC). METHODS: This prospective,
      multicenter, open-label, historical controlled, single-arm study transitioned
      patients who had primary open-angle glaucoma, pigment dispersion glaucoma, or
      ocular hypertension and who required further IOP reduction from PGA monotherapy
      to once-daily treatment with TTFC for 12 weeks. IOP and safety (adverse events,
      corrected distance visual acuity, and slit-lamp biomicroscopy) were assessed at
      baseline, week 4, and week 12. A solicited ocular symptom survey was administered
      at baseline and at week 12. Patients and investigators reported their medication
      preference at week 12. RESULTS: Of 65 patients enrolled, 43 had received prior
      travoprost therapy and 22 had received prior nontravoprost therapy (n = 18,
      bimatoprost; n = 4, latanoprost). In the total population, mean IOP was
      significantly reduced from baseline (P = 0.000009), showing a 16.8% reduction
      after 12 weeks of TTFC therapy. In the study subgroups, mean IOP was
      significantly reduced from baseline to week 12 (P = 0.0001) in the prior
      travoprost cohort (19.0% reduction) and in the prior nontravoprost cohort (13.1%
      reduction). Seven mild, ocular, treatment-related adverse events were reported.
      Of the ten ocular symptom questions, eight had numerically lower percentages with
      TTFC compared with prior PGA monotherapy and two had numerically higher
      percentages with TTFC (dry eye symptoms and ocular stinging/burning). At week 12,
      TTFC was preferred over prior therapy for 84.2% of patients (48 of 57) by the
      patients themselves, and for 94.7% of patients (54 of 57) by their physicians.
      CONCLUSION: When TTFC replaced PGA monotherapy in patients whose IOP had been
      uncontrolled, the outcome was a significant reduction in IOP and an acceptable
      safety and tolerability profile. Most patients and investigators preferred TTFC
      to prior PGA monotherapy.

PMID- 22654497
TI  - Aggressive retinal astrocytoma associated with tuberous sclerosis.
AB  - We report the case of a patient with an aggressive retinal astrocytoma
      accompanied with macular edema and neovascular vessels, who was initially treated
      with intravitreal bevacizumab injections. A 24-year-old male presented to our
      clinic complaining of visual disturbance in his right eye. At 8 years of age, he
      had been diagnosed as having tuberous sclerosis complex. Fundus examination
      demonstrated a retinal tumor accompanied with marked neovascular vessels on the
      surface, retinal hemorrhage, and macular edema. After six monthly intravitreal
      bevacizumab injections, fundus examination demonstrated marked regression of the
      macular edema and neovascular vessels. Two months later, a vitreous hemorrhage
      developed which necessitated pars plana vitrectomy. After additional intravitreal
      bevacizumab injection for preventing intraoperative bleeding, vitrectomy with
      endophotocoagulation for the tumor was performed. The vitreous sample was
      obtained during vitrectomy, and we measured the vascular endothelial growth
      factor concentration by enzyme-linked immunosorbent assay. The surgically removed
      epiretinal neovascular membrane and biopsied retinal tumor expressed vascular
      endothelial growth factor, although several intravitreal bevacizumab injections
      led to a vitreous vascular endothelial growth factor concentration of
      undetectable levels. The clinical course and immunohistochemical analyses
      indicate that intravitreal bevacizumab monotherapy may have been insufficient to
      treat the aggressive retinal astrocytoma with macular edema and that laser
      photocoagulation or photodynamic therapy for the tumor should be considered
      following intravitreal bevacizumab injection in such cases.

PMID- 22654498
TI  - Successful salvage therapy of Fusarium endophthalmitis secondary to keratitis: an
      interventional case series.
AB  - PURPOSE: To describe a combination of treatment modalities used for the
      successful eradication of Fusarium endophthalmitis. DESIGN: Interventional case
      series. PARTICIPANTS: Three consecutive patients with keratitis-associated
      Fusarium endophthalmitis. METHODS: After failure of traditional management
      options, a combination of intravitreal and long-term, high-dose systemic
      voriconazole, topical antifungal medications, and surgical intervention, with
      penetrating keratoplasty, lensectomy, and endoscopic-guided pars plana
      vitrectomy, was administered to each patient. RESULTS: All three cases achieved
      full resolution of the infection, with a final Snellen visual acuity score of
      20/50 to 20/70. CONCLUSIONS: An aggressive combination of therapeutic modalities,
      including the removal of subiris abscesses, might be needed for the successful
      resolution of Fusarium endophthalmitis.

PMID- 22654499
TI  - A new eye gel containing sodium hyaluronate and xanthan gum for the management of
      post-traumatic corneal abrasions.
AB  - PURPOSE: The aim of this study was to investigate the effects of an ophthalmic
      gel containing sodium hyaluronate and xanthan gum in addition to the antibiotic
      netilmicin in the management of traumatic corneal abrasions. PATIENTS AND
      METHODS: PATIENTS WITH TRAUMATIC CORNEAL ABRASIONS WERE RANDOMLY TREATED AS
      FOLLOWS: Group A (n = 20) with an occlusive patching for 12 hours plus one drop
      of an eye gel containing 0.15% sodium hyaluronate, 1% xanthan gum and 0.3%
      netilmicin qid for 5 days; and Group B (n = 20) with an occlusive patching for 2
      3 days plus one application of 0.3% netilmicin ophthalmic ointment qid for 5
      days. All patients were evaluated after the third and seventh day by slit-lamp
      examination, fluorescein staining, and corneal defect photograph in order to
      assess corneal re-epithelialization. Conjunctival hyperaemia, lid oedema,
      subjective symptoms of discomfort, and conjunctival swabs were also evaluated.
      RESULTS: No statistically significant difference was observed between the groups
      in terms of the extent of corneal healing after 3 days of treatment. Both
      treatments were also highly effective in decreasing the erosion score and the
      conjunctival hyperemia (P < 0.0001, P < 0.005, respectively) without any
      significant difference between the two types of treatment. Subjective symptoms of
      discomfort and conjunctival swabs were also evaluated. CONCLUSION: In the
      management of traumatic corneal abrasions, the administration of an eye gel
      containing sodium hyaluronate and xanthan gum is able to reduce the length of
      occlusive patching. In addition, the presence of netilmicin guarantees good
      antibiotic prophylaxis during the wound repair process.

PMID- 22654500
TI  - Intraocular infections in the neonatal intensive care unit.
AB  - BACKGROUND: The purpose of this study was to report on the incidence and
      treatment outcomes of endogenous endophthalmitis among newborns in the neonatal
      intensive care unit (NICU) of a single medical center. METHODS: This was a
      noncomparative, retrospective case series of endogenous endophthalmitis among
      infants at the Jackson Memorial Hospital NICU treated between March 1, 2002 and
      March 1, 2007. RESULTS: Of 4323 infants admitted to the NICU, seven eyes of six
      (0.139%) infants (two males, four females) were diagnosed with endophthalmitis
      during the study period. Four patients were born prematurely with a mean
      gestational age of 27.5 weeks and a mean birth weight of 1153 g. Retinopathy of
      prematurity was reported in two of the six patients. Mean follow-up was 3.5
      years. The diagnosis was confirmed by positive cultures or polymerase chain
      reaction testing at a median age of 34 postnatal days. Positive cultures included
      Candida albicans (n = 4), Pseudomonas aeruginosa (n = 1), and Herpes simplex type
      2 (n = 1). All patients received systemic treatment and five received adjunctive
      ophthalmic interventions, including intravitreal antibiotics in five eyes of four
      patients and vitrectomy with pars plana lensectomy in three eyes. One patient
      underwent primary enucleation and another had delayed evisceration. In the
      remaining five eyes, there was a normal appearing posterior segment and normal
      intraocular pressures at last follow-up. CONCLUSION: Endogenous endophthalmitis
      is a rare complication in infants in the NICU, but may occur in patients with
      candidemia, bacteremia, retinopathy of prematurity, and low birth weight. Despite
      early and appropriate treatment, involved eyes may have poor outcomes.

PMID- 22654501
TI  - Multicenter, prospective, open-label, observational study of bimatoprost 0.01% in
      patients with primary open-angle glaucoma or ocular hypertension.
AB  - BACKGROUND: Bimatoprost 0.01% was developed for improved tolerability over
      bimatoprost 0.03%, while maintaining efficacy in lowering intraocular pressure
      (IOP). This multicenter, prospective, open-label, observational study was
      designed to investigate the efficacy and tolerability of bimatoprost 0.01% in
      routine clinical practice. METHODS: Data were collected from 10,337 patients with
      primary open-angle glaucoma or ocular hypertension attending 1334 centers in
      Germany. The primary efficacy outcome was mean change in IOP in each eye from
      baseline to 10-14 weeks after initiation of bimatoprost 0.01%. Target IOP, prior
      therapies, additional treatments, and adverse events were also assessed. All
      treatment decisions were at the physicians' discretion. RESULTS: Bimatoprost
      0.01% significantly lowered mean IOP from baseline by -4.1 mmHg (P < 0.0001) in
      all patients after a mean of 10.45 weeks. In patients without previous treatment,
      bimatoprost 0.01% reduced mean IOP from baseline by -6.5 mmHg (P < 0.0001).
      Bimatoprost 0.01% also significantly reduced IOP in patients previously treated
      with monotherapy of beta-blockers, prostaglandin analogs, carbonic anhydrase
      inhibitors or bimatoprost 0.03%. No adverse events were reported by 93.9% of
      patients during treatment with bimatoprost 0.01%; the most commonly reported
      adverse events were eye irritation (2.0%), ocular hyperemia (1.4%), and
      conjunctival hyperemia (1.2%). Physicians and patients rated tolerability and
      adherence as high, and most patients said they would continue with bimatoprost
      0.01% treatment. CONCLUSION: Bimatoprost 0.01% can produce additional IOP
      lowering effects when used in routine clinical practice in patients who have
      received prior therapy, in addition to lowering IOP in previously untreated
      patients. A high rate of continuation of therapy with bimatoprost 0.01% was
      observed in patients who switched from a variety of different medications. The
      results suggest that bimatoprost 0.01% is a suitable first-choice therapy in
      patients with primary open-angle glaucoma or ocular hypertension.

PMID- 22654502
TI  - Update on peripheral ulcerative keratitis.
AB  - Ulcerative inflammation of the cornea occurs in the perilimbal cornea, and is
      associated with autoimmune collagen vascular and arthritic diseases. Rheumatoid
      arthritis is the most frequent underlying disease. The tendency for peripheral
      location is due to the distinct morphologic and immunologic characteristics of
      the limbal conjunctiva, which provides access for circulating immune complexes to
      the peripheral cornea via the capillary network. Deposition of immune complexes
      in the terminal ends of limbal vessels initiates immune-mediated vasculitis, and
      causes inflammatory cell and protein leakage due to vessel wall damage.
      Development of peripheral ulcerative keratitis associated with systemic disease
      may represent worsening of a potentially life-threatening disease. Accompanying
      scleritis, particularly the necrotizing form, is usually observed in severe
      cases, which may result in corneal perforation and loss of vision. Although first
      line treatment with systemic corticosteroids is indicated for acute phases,
      immunosuppressive and cytotoxic agents are required for treatment of peripheral
      ulcerative keratitis associated with multisystem disorders. Recently, infliximab,
      a chimeric antibody against proinflammatory cytokine tumor necrosis factor-alpha,
      was reported to be effective in cases refractory to conventional immunomodulatory
      therapy. The potential side effects of these therapies require close follow-up
      and regular laboratory surveillance.

PMID- 22654503
TI  - Annual direct cost of dry eye in Japan.
AB  - BACKGROUND: This study was performed to estimate the annual direct cost incurred
      by dry eye patients, which includes expenses for treatment and drugs, as well as
      the cost of punctal plugs. METHODS: The study group consisted of 118 dry eye
      patients aged 20 years or older who visited any of the 15 medical care facilities
      that participated in this prospective cohort dry eye study. We estimated annual
      direct costs from outpatient medical records and survey questionnaires obtained
      from patients. RESULTS: Of the total patients enrolled, 10 were men and 108
      women, and their average age was 64.1 +/- 11.2 years. The number of hospital
      visits made by patients was 5.8 +/- 3.6 per year. Among those who used ophthalmic
      solutions, the numbers of bottles used per year were as follows: 32.1 +/- 20.8
      bottles of hyaluronic acid ophthalmic solution (87 patients), 53.1 +/- 42.2
      bottles of artificial tears (40 patients), and 33.2 +/- 23.2 bottles of over-the
      counter eyedrops (15 patients). In patients with punctal plugs, 4.1 +/- 3.9 plugs
      were used annually. The annual drug cost was 32,000 +/- 21,675 Japanese yen (323
      +/- 219 US dollars). The clinical cost was 16,318 +/- 9961 Japanese yen (165 +/-
      101 US dollars). The total direct costs including punctal plug treatment amounted
      to 52,467 +/- 38,052 Japanese yen (530 +/- 384 US dollars). CONCLUSION: Although
      treatment modalities for dry eye in Japan were different from those in the US and
      in European countries, the direct cost of dry eye patients in Japan was
      comparable with that reported in those countries. Considering the high prevalence
      of dry eye, the direct cost of this chronic condition may be significant.

PMID- 22654505
TI  - Unique sex-based approach identifies transcriptomic biomarkers associated with
      non-syndromic craniosynostosis.
AB  - BACKGROUND: The premature fusion of one cranial suture, also referred to as non
      syndromic craniosynostosis, most commonly involves premature fusion of the
      sagittal, coronal, or metopic sutures, in that order. Population-based
      epidemiological studies have found that the birth prevalence of single-suture
      craniosynostosis is both suture- and sex-dependent. METHODS: Transcriptomic data
      from 199 individuals with isolated sagittal (n = 100), unilateral coronal (n =
      50), and metopic (n = 49) synostosis were compared against a control population
      (n = 50) to identify transcripts accounting for the different sex-based
      frequencies observed in this disease. RESULTS: Differential sex-based gene
      expression was classified as either gained (divergent) or lost (convergent) in
      affected individuals to identify transcripts related to disease predilection.
      Divergent expression was dependent on synostosis sub-type, and was extensive in
      metopic craniosynostosis specifically. Convergent microarray-based expression was
      independent of synostosis sub-type, with convergent expression of FBN2, IGF2BP3,
      PDE1C and TINAGL1 being the most robust across all synostosis sub-types.
      CONCLUSIONS: Analysis of sex-based gene expression followed by validation by qRT
      PCR identified that concurrent upregulation of FBN2 and IGF2BP3, and
      downregulation of TINAGL1 in craniosynostosis cases were all associated with
      increased RUNX2 expression and may represent a transcriptomic signature that can
      be used to characterize a subset of single-suture craniosynostosis cases.

PMID- 22654504
TI  - Quantification of Transcriptome Responses of the Rumen Epithelium to Butyrate
      Infusion using RNA-seq Technology.
AB  - Short-chain fatty acids (SCFAs), such as butyrate, produced by gut
      microorganisms, play a critical role in energy metabolism and physiology of
      ruminants as well as in human health. In this study, the temporal effect of
      elevated butyrate concentrations on the transcriptome of the rumen epithelium was
      quantified via serial biopsy sampling using RNA-seq technology. The mean number
      of genes transcribed in the rumen epithelial transcriptome was 17,323.63 +/-
      277.20 (+/-SD; N = 24) while the core transcriptome consisted of 15,025 genes.
      Collectively, 80 genes were identified as being significantly impacted by
      butyrate infusion across all time points sampled. Maximal transcriptional effect
      of butyrate on the rumen epithelium was observed at the 72-h infusion when the
      abundance of 58 genes was altered. The initial reaction of the rumen epithelium
      to elevated exogenous butyrate may represent a stress response as Gene Ontology
      (GO) terms identified were predominantly related to responses to bacteria and
      biotic stimuli. An algorithm for the reconstruction of accurate cellular networks
      (ARACNE) inferred regulatory gene networks with 113,738 direct interactions in
      the butyrate-epithelium interactome using a combined cutoff of an error tolerance
      (E = 0.10) and a stringent P-value threshold of mutual information (5.0 * 10(
      11)). Several regulatory networks were controlled by transcription factors, such
      as CREBBP and TTF2, which were regulated by butyrate. Our findings provide
      insight into the regulation of butyrate transport and metabolism in the rumen
      epithelium, which will guide our future efforts in exploiting potential
      beneficial effect of butyrate in animal well-being and human health.

PMID- 22654506
TI  - Requirements for acquiring a high-quality house dust mite extract for allergen
      immunotherapy.
AB  - The house dust mite is a major cause of respiratory allergy worldwide. The
      management of mite allergy is based on avoidance measures, drug treatment, and
      allergen immunotherapy, but only allergen immunotherapy is able to modify the
      natural history of the disease. Injectable subcutaneous immunotherapy was
      introduced a century ago, while sublingual immunotherapy was proposed in the
      1980s and emerged in the ensuing years as an effective and safe option to
      subcutaneous immunotherapy. However, the quality of the extracts to be used in
      allergen immunotherapy is crucial for the success of treatment. The mite extract
      for sublingual immunotherapy known as Staloral 300 was developed to offer optimal
      characteristics concerning the mite culture medium, standardization, and allergen
      dose. Double-blind, placebo-controlled trials with Staloral 300 have provided a
      substantial part of the clinical evidence analyzed in a meta-analysis of the
      efficacy of allergen immunotherapy in mite-induced rhinitis and asthma. Safety
      and tolerability are very good, mild local reactions in the mouth being the most
      common side effect. This makes it feasible to carry out sublingual immunotherapy
      for the 3-5-year duration needed to achieve long-lasting tolerance to the
      specific allergen. The performance of Staloral 300 may provide optimal conditions
      for an effective and safe sublingual immunotherapy in patients with mite-induced
      respiratory allergy.

PMID- 22654507
TI  - Evaluating the psychometric properties of the attitudes towards depression and
      its treatments scale in an Australian sample.
AB  - BACKGROUND: Individuals' attitudes towards depression and its treatments may
      influence their likelihood of seeking professional help and adherence to
      treatment when depressed. Objective measures, such as the Attitudes Towards
      Depression and its Treatments scale (ATDT), have been developed to assess such
      attitudes. The aims of this research were to test the reliability and validity of
      ATDT on an Australian sample who were not depressed during the study or who had
      previously been depressed, to explore the attitudes of the Australian public
      towards depression, and to compare these attitudes to those of a Canadian sample
      of people with depression. METHODS: A sample of 63 males and 140 females (mean
      age = 32.2 years, SD = 12.9 years) from Melbourne, Australia took part in this
      study. Fourteen of the males and 52 of the female participants (mean age = 35.4
      years, SD = 13.2 years) stated that they had been previously diagnosed with
      depression. RESULTS: THE ATTITUDES OF THE AUSTRALIAN SAMPLE AND THE SUBSET OF
      THAT SAMPLE WHO HAD PREVIOUSLY EXPERIENCED DEPRESSION DIFFERED FROM THOSE OF THE
      CANADIAN OUTPATIENT SAMPLE: they were less ashamed of depression, more likely to
      take antidepressants and consider psychotherapy, and more likely to seek help
      from professionals or significant others in their lives. However, those in the
      Australian sample were more likely to report that antidepressants made them lose
      control, and they were less willing to consider electric shock as a treatment
      option for their depression. The internal reliability as measured by Cronbach's
      alpha was lower in the current study (0.63 and 0.57 for both the general public
      and the depressed Australian sample) than in the Canadian study. Confirmatory
      factor analysis failed to replicate the factor structure reported previously.
      LIMITATIONS: The Australian sample of this study may be underrepresentative due
      to the sampling methods used, and the high proportion of females should not be
      overlooked. CONCLUSION: Researchers should be vigilant when utilizing measures
      constructed in different countries. In comparison to the Canadians, the selected
      Australian sample had more positive attitudes towards depression and its
      available treatments. The ATDT scale was not a reliable and valid measure in this
      sample.

PMID- 22654509
TI  - Beliefs about antipsychotic versus hypoglycemic medications among individuals
      with serious mental illness and type 2 diabetes.
AB  - BACKGROUND: This study compared the beliefs held by individuals with coexisting
      serious mental illness and type 2 diabetes regarding the necessity and risks of
      taking antipsychotic versus hypoglycemic medications. We also investigated
      whether nonadherent patients differed from adherent patients in their beliefs
      about medications. METHODS: Forty-four individuals with type 2 diabetes and
      serious mental illness who were prescribed hypoglycemic and antipsychotic
      medications completed a cross-sectional assessment of medication beliefs and
      adherence for both medication types. RESULTS: Patients perceived a greater need
      for hypoglycemic versus antipsychotic medications; however, their beliefs were
      not associated with nonadherence to either medication type. CONCLUSION: These
      results suggest that individuals with coexisting serious mental illness and type
      2 diabetes have stronger convictions regarding the necessity of their diabetes
      medication for maintaining their health.

PMID- 22654508
TI  - Treatment-resistant depression: therapeutic trends, challenges, and future
      directions.
AB  - BACKGROUND: Patients with major depression respond to antidepressant treatment,
      but 10%-30% of them do not improve or show a partial response coupled with
      functional impairment, poor quality of life, suicide ideation and attempts, self
      injurious behavior, and a high relapse rate. The aim of this paper is to review
      the therapeutic options for treating resistant major depressive disorder, as well
      as evaluating further therapeutic options. METHODS: In addition to Google Scholar
      and Quertle searches, a PubMed search using key words was conducted, and relevant
      articles published in English peer-reviewed journals (1990-2011) were retrieved.
      Only those papers that directly addressed treatment options for treatment
      resistant depression were retained for extensive review. RESULTS: Treatment
      resistant depression, a complex clinical problem caused by multiple risk factors,
      is targeted by integrated therapeutic strategies, which include optimization of
      medications, a combination of antidepressants, switching of antidepressants, and
      augmentation with non-antidepressants, psychosocial and cultural therapies, and
      somatic therapies including electroconvulsive therapy, repetitive transcranial
      magnetic stimulation, magnetic seizure therapy, deep brain stimulation,
      transcranial direct current stimulation, and vagus nerve stimulation. As a
      corollary, more than a third of patients with treatment-resistant depression tend
      to achieve remission and the rest continue to suffer from residual symptoms. The
      latter group of patients needs further study to identify the most effective
      therapeutic modalities. Newer biomarker-based antidepressants and other drugs,
      together with non-drug strategies, are on the horizon to address further the
      multiple complex issues of treatment-resistant depression. CONCLUSION: Treatment
      resistant depression continues to challenge mental health care providers, and
      further relevant research involving newer drugs is warranted to improve the
      quality of life of patients with the disorder.

PMID- 22654510
TI  - Preliminary support for the construct of health care empowerment in the context
      of treatment for human immunodeficiency virus.
AB  - BACKGROUND: The Model of Health Care Empowerment (HCE) defines HCE as the process
      and state of being engaged, informed, collaborative, committed, and tolerant of
      uncertainty regarding health care. We examined the hypothesized antecedents and
      clinical outcomes of this model using data from ongoing human immunodeficiency
      virus (HIV)-related research. The purpose of this paper is to explore whether a
      new measure of HCE offers direction for understanding patient engagement in HIV
      medical care. Using data from two ongoing trials of social and behavioral aspects
      of HIV treatment, we examined preliminary support for hypothesized clinical
      outcomes and antecedents of HCE in the context of HIV treatment. METHODS: This
      was a cross-sectional analysis of 12-month data from study 1 (a longitudinal
      cohort study of male couples in which one or both partners are HIV-seropositive
      and taking HIV medications) and 6-month data from study 2, a randomized
      controlled trial of HIV-seropositive persons not on antiretroviral therapy at
      baseline despite meeting guidelines for treatment. From studies 1 and 2, 254 and
      148 participants were included, respectively. Hypothesized antecedents included
      cultural/social/environmental factors (demographics, HIV-related stigma),
      personal resources (social problem-solving, treatment knowledge and beliefs,
      treatment decision-making, shared decision-making, decisional balance, assertive
      communication, trust in providers, personal knowledge by provider, social
      support), and intrapersonal factors (depressive symptoms, positive/negative
      affect, and perceived stress). Hypothesized clinical outcomes of HCE included
      primary care appointment attendance, antiretroviral therapy use, adherence self
      efficacy, medication adherence, CD4+ cell count, and HIV viral load. RESULTS:
      Although there was no association observed between HCE and HIV viral load and
      CD4+ cell count, there were significant positive associations of HCE scores with
      likelihood of reporting a recent primary care visit, greater treatment adherence
      self-efficacy, and higher adherence to antiretroviral therapy. Hypothesized
      antecedents of HCE included higher beliefs in the necessity of treatment and
      positive provider relationships.

PMID- 22654511
TI  - Retrospective and observational study to assess the efficacy of citicoline in
      elderly patients suffering from stupor related to complex geriatric syndrome.
AB  - A significant percentage of elderly subjects (50%-80%) suffering from sub-acute
      ischemic cerebrovascular disease, with or without moderate or severe cognitive
      memory decline and with or without associated behavioral and psychological
      symptoms, shows a complex syndrome. This syndrome is related to the progressive
      impairment of health conditions and/or stressing events (ie, hospitalization),
      characterized by confusion and/or stupor, which are consequently difficult to
      manage and require a great deal of care. Geriatric patients often suffer from
      multiple chronic illnesses, may take numerous medications daily, exhibit clinical
      instability, and may experience worsening of medical conditions following
      cerebral ischemic events and thus have an increased risk of disability and
      mortality. There are several studies in literature which demonstrate the efficacy
      of citicoline, thanks to its neuroprotective function, for the recovery and in
      postischemic cerebral rehabilitation. It has been shown that, even soon after an
      ischemic stroke, administration of oral citicoline (500-4000 mg/day) improves the
      general conditions evaluated with the Rankin scale and the National Institute of
      Health Stroke Scale 12. In particular, it has been shown that the CDP-choline
      improves the cognitive and mental performance in Alzheimer's dementia and
      vascular dementia. We have evaluated the administration of citicoline in
      geriatric patients following a protocol of intravenous study on improvement of
      individual performances.

PMID- 22654512
TI  - Comparison of multisensory and strength training for postural control in the
      elderly.
AB  - OBJECTIVE: The objective of this study was to analyze the efficacy of
      multisensory versus muscle strengthening to improve postural control in healthy
      community-dwelling elderly. PARTICIPANTS: We performed a single-blinded study
      with 46 community-dwelling elderly allocated to strength (GS, n = 23; 70.18 +/-
      4.8 years 22 women and 1 man) and multisensory exercises groups (GM, n = 23; 68.8
      +/- 5.9 years; 22 women and 1 man) for 12 weeks. METHODS: We performed isokinetic
      evaluations of muscle groups in the ankle and foot including dorsiflexors,
      plantar flexors, inversion, and eversion. The oscillation of the center of
      pressure was assessed with a force platform. RESULTS: The GM group presented a
      reduction in the oscillation (66.8 +/- 273.4 cm(2) to 11.1 +/- 11.6 cm(2); P =
      0.02), which was not observed in the GS group. The GM group showed better results
      for the peak torque and work than the GS group, but without statistical
      significance. CONCLUSION: Although the GM group presented better results, it is
      not possible to state that one exercise regimen proved more efficacious than the
      other in improving balance control.

PMID- 22654513
TI  - Cascade search for HSV-1 combinatorial drugs with high antiviral efficacy and low
      toxicity.
AB  - BACKGROUND: Infectious diseases cause many molecular assemblies and pathways
      within cellular signaling networks to function aberrantly. The most effective way
      to treat complex, diseased cellular networks is to apply multiple drugs that
      attack the problem from many fronts. However, determining the optimal combination
      of several drugs at specific dosages to reach an endpoint objective is a daunting
      task. METHODS: In this study, we applied an experimental feedback system control
      (FSC) method and rapidly identified optimal drug combinations that inhibit herpes
      simplex virus-1 infection, by only testing less than 0.1% of the total possible
      drug combinations. RESULTS: Using antiviral efficacy as the criterion, FSC
      quickly identified a highly efficacious drug cocktail. This cocktail contained
      high dose ribavirin. Ribavirin, while being an effective antiviral drug, often
      induces toxic side effects that are not desirable in a therapeutic drug
      combination. To screen for less toxic drug combinations, we applied a second FSC
      search in cascade and used both high antiviral efficacy and low toxicity as
      criteria. Surprisingly, the new drug combination eliminated the need for
      ribavirin, but still blocked viral infection in nearly 100% of cases. CONCLUSION:
      This cascade search provides a versatile platform for rapid discovery of new drug
      combinations that satisfy multiple criteria.

PMID- 22654514
TI  - Liposomes bearing fibrinogen could potentially interfere with platelet
      interaction and procoagulant activity.
AB  - BACKGROUND: The contribution of fibrinogen (FBN) to hemostasis acting on platelet
      aggregation and clot formation is well established. It has been suggested that
      FBN-coated liposomes could be useful in restoring hemostasis. In the present
      study, we evaluated the modifications induced by multilamellar raw liposomes
      (MLV) or fibrinogen-coated liposomes (MLV-FBN) on hemostatic parameters.
      MATERIALS AND METHODS: Different experimental settings using whole blood or
      thrombocytopenic blood were used. Thromboelastometry, aggregation studies,
      platelet function analyzer (PFA-100((r))) tests and studies under flow conditions
      were applied to detect the effect of MLV-FBN on hemostatic parameters. RESULTS:
      The presence of MLV-FBN in whole blood modified its viscoelastic properties,
      prolonging clot formation time (CFT) (226.5 +/- 26.1 mm versus 124.1 +/- 9.4 mm;
      P < 0.01) but reducing clot firmness (45.4 +/- 1.8 mm versus 35.5 +/- 2.3 mm; P <
      0.05). Under thrombocytopenic conditions, FIBTEM analysis revealed that MLV-FBN
      shortened clotting time (CT) compared to MLV (153.3 +/- 2.8 s versus 128.0 +/-
      4.6 s; P < 0.05). Addition of either liposome decreased fibrin formation on the
      subendothelium (MLV 8.1% +/- 4.7% and MLV-FBN 0.8% +/- 0.5% versus control 36.4%
      +/- 6.7%; P < 0.01), whereas only MLV-FBN significantly reduced fibrin deposition
      in thrombocytopenic blood (14.4% +/- 6.3% versus control 34.5% +/- 5.2%; P <
      0.05). MLV-FBN inhibited aggregation induced by arachidonic acid (52.1% +/- 8.1%
      versus 88.0% +/- 2.1% in control; P < 0.01) and ristocetin (40.3% +/- 8.8% versus
      94.3% +/- 1.1%; P < 0.005), but it did not modify closure times in PFA-100((r))
      studies. In perfusion experiments using whole blood, MLV and MLV-FBN decreased
      the covered surface (13.25% +/- 2.4% and 9.85% +/- 2.41%, respectively, versus
      control 22.0% +/- 2.0%; P < 0.01) and the percentage of large aggregates (8.4% +/
      2.3% and 3.3% +/- 1.01%, respectively, versus control 14.6% +/- 1.8%; P < 0.01).
      CONCLUSION: Our results reveal that, in addition to the main contribution of
      fibrinogen to hemostasis, MLV-FBN inhibits platelet-mediated hemostasis and
      coagulation mechanisms.

PMID- 22654515
TI  - Peptides complementary to the active loop of porin P2 from Haemophilus influenzae
      modulate its activity.
AB  - Haemophilus influenzae type b (Hib) is one of the leading causes of invasive
      bacterial infection in young children. It is characterized by inflammation that
      is mainly mediated by cytokines and chemokines. One of the most abundant
      components of the Hib outer membrane is the P2 porin, which has been shown to
      induce the release of several inflammatory cytokines. A synthetic peptide
      corresponding to loop L7 of the porin activates JNK and p38 mitogen-activated
      protein kinase (MAPK) pathways. We report a novel use of the complementary
      peptide approach to design a peptide that is able to bind selectively to the
      protein P2, thereby reducing its activity. This work provides insights into
      essential molecular details of P2 that may affect the pathogenesis of Hib
      infections where interruption of the signaling cascade could represent an
      attractive therapeutic strategy.

PMID- 22654516
TI  - Efficacy and safety of nanohybrids comprising silver nanoparticles and silicate
      clay for controlling Salmonella infection.
AB  - Developing effective and safe drugs is imperative for replacing antibiotics and
      controlling multidrug-resistant microbes. Nanoscale silicate platelet (NSP) and
      its nanohybrid, silver nanoparticle/NSP (AgNP/NSP), have been developed, and the
      nanohybrids show a strong and general antibacterial activity in vitro. Here,
      their efficacy for protecting Salmonella-infected chicks from fatality and
      septicemia was evaluated. Both orally administrated NSP and AgNP/NSP, but not
      AgNPs alone, effectively reduced the systemic Salmonella infection and mortality.
      In addition, quantitative Ag analyses demonstrated that Ag deposition from
      AgNP/NSP in the intestines was less than that from conventional AgNPs, indicating
      that the presence of NSP for immobilizing AgNPs reduced Ag accumulation in tissue
      and improved the safety of AgNPs. These in vivo results illustrated that both NSP
      and AgNP/NSP nanohybrid represent potential agents for controlling enteric
      bacterial infections.

PMID- 22654517
TI  - Lipidic nanocapsule drug delivery: neuronal protection for cochlear implant
      optimization.
AB  - OBJECTIVE: Sensorineural hearing loss leads to the progressive degeneration of
      spiral ganglion cells (SGC). Next to postoperative fibrous tissue growth, which
      should be suppressed to assure a close nerve-electrode interaction, the density
      of healthy SGC is one factor that influences the efficiency of cochlear implants
      (CI), the choice of treatment for affected patients. Rolipram, a
      phosphodiesterase-4 inhibitor, has proven neuroprotective and anti-inflammatory
      effects and might also reduce SGC degeneration and fibrosis, but it has to pass
      the cellular membrane to be biologically active. METHODS: Lipidic nanocapsules
      (LNC) can be used as biodegradable drug carriers to increase the efficacy of
      conventional application methods. We examined the biological effects of rolipram
      and LNC's core encapsulated rolipram on SGC and dendritic cell (DC) tumor
      necrosis factor-alpha (TNF-alpha) production in vitro and on SGC survival in
      systemically-deafened guinea pigs in vivo. RESULTS: Our results prove that
      rolipram does not have a beneficial effect on cultured SGC. Incorporation of
      rolipram in LNC increased the survival of SGC significantly. In the DC study,
      rolipram significantly inhibited TNF-alpha in a dose-dependent manner. The
      rolipram-loaded LNC provided a significant cytokine inhibition as well. In vivo
      data do not confirm the in vitro results. CONCLUSION: By transporting rolipram
      into the SGC cytoplasm, LNC enabled the neuroprotective effect of rolipram in
      vitro, but not in vivo. This might be due to dilution of test substances by
      perilymph or an inadequate release of rolipram based on differing in vivo and in
      vitro conditions. Nevertheless, based on in vitro results, proving a
      significantly increased neuronal survival when using LNC-rolipram compared to
      pure rolipram and pure LNC application, we believe that the combination of
      rolipram and LNC can potentially reduce neuronal degeneration and fibrosis after
      CI implantation. We conclude that rolipram is a promising drug that can be used
      in inner ear therapy and that LNC have potential as an inner ear drug-delivery
      system. Further experiments with modified conditions might reveal in vivo
      biological effects.

PMID- 22654520
TI  - Pharmacological approaches to the management of type 2 diabetes in fasting adults
      during Ramadan.
AB  - More than 50 million Muslims throughout the world with type 2 diabetes mellitus
      (T2DM) fast for one lunar month (Ramadan) each year. Health care providers within
      and outside the Muslim world need to be aware of the nature of these partial days
      of fasting and their risks (and potential benefits) to people with T2DM, and need
      to provide Ramadan-adjusted diabetes care. Hypoglycemia during the fasting days
      represents the greatest health risk for these patients; hence, diabetes-related
      pharmacotherapy needs to be tailored and adjusted with this risk in mind. With
      limited trial data available, this review proposes practical modifications to the
      usual pre-Ramadan antidiabetic regimens that are based on pathophysiological
      principles, clinical trial evidence (where available), expert opinion, and
      extended practical experience. Individualization of care is paramount in this
      regard to take into consideration the patient and societal, cultural, and
      economic variables.

PMID- 22654521
TI  - Potent antiatherosclerotic effects of alogliptin in addition to its potent
      antidiabetic effects.

PMID- 22654519
TI  - Clinical features and treatment of maturity onset diabetes of the young (MODY).
AB  - Maturity onset diabetes of the young (MODY) is a heterogeneous group of disorders
      that result in beta-cell dysfunction. It is rare, accounting for just 1%-2% of
      all diabetes. It is often misdiagnosed as type 1 or type 2 diabetes, as it is
      often difficult to distinguish MODY from these two forms. However, diagnosis
      allows appropriate individualized care, depending on the genetic etiology, and
      allows prognostication in family members. In this review, we discuss features of
      the common causes of MODY, as well as the treatment and diagnosis of MODY.

PMID- 22654518
TI  - Pharmacological management of binge eating disorder: current and emerging
      treatment options.
AB  - Growing evidence suggests that pharmacotherapy may be beneficial for some
      patients with binge eating disorder (BED), an eating disorder characterized by
      repetitive episodes of uncontrollable consumption of abnormally large amounts of
      food without inappropriate weight loss behaviors. In this paper, we provide a
      brief overview of BED and review the rationales and data supporting the
      effectiveness of specific medications or medication classes in treating patients
      with BED. We conclude by summarizing these data, discussing the role of
      pharmacotherapy in the BED treatment armamentarium, and suggesting future areas
      for research.

PMID- 22654522
TI  - Close association between polymorphisms of the nitric oxide synthetase 3 gene and
      neurological disorders other than stroke.

PMID- 22654523
TI  - Out-of-office blood pressure: from measurement to control.
AB  - Hypertension is an important risk factor for the development of cardiovascular
      disease, and is a major cause of morbidity and mortality worldwide.
      Traditionally, hypertension diagnosis and treatment and clinical evaluations of
      antihypertensive efficacy have been based on office blood pressure (BP)
      measurements; however, there is increasing evidence that office measures may
      provide inadequate or misleading estimates of a patient's true BP status and
      level of cardiovascular risk. The introduction, and endorsement by treatment
      guidelines, of 24-hour ambulatory BP monitoring and self (or home) BP monitoring
      has facilitated more reliable and reproducible estimations of true BP, including
      the identification of white-coat and masked hypertension, and evaluation of BP
      variability. In addition, ambulatory BP monitoring enables accurate assessment of
      treatment effectiveness over 24 hours and both ambulatory and self BP monitoring
      may lead to better tailoring of therapy according to BP profile and concomitant
      disease. This review describes the clinical benefits and limitations of out-of
      office assessments and their applications for effective management of
      hypertension and attainment of BP control.

PMID- 22654524
TI  - Prevalence of psychiatric disorders and associated risk factors in women during
      their postpartum period: a major public health problem and global comparison.
AB  - BACKGROUND: Postnatal depression has received considerable research and clinical
      attention; however, anxiety and stress in postpartum women have been relatively
      neglected. OBJECTIVE: The aim of this study was to determine the prevalence of
      depression, anxiety, and stress during the postpartum period of women using the
      Depression Anxiety Stress Scales, and to examine the associated correlates of
      these conditions. DESIGN: This was a cross-sectional study conducted from January
      2010 to May 2011. SETTING: Primary health care centers of the State of Qatar
      Supreme Council of Health. SUBJECTS: A representative sample of 2091 women who
      attended primary health care centers was surveyed. From this sample, 1659 women
      (79.3%) consented to participate in the study. METHODS: The study was based on a
      face-to-face interview using a designed questionnaire covering sociodemographic
      characteristics, family history, medical history, the obstetric variables of
      patients, and stressful life events. Depression, anxiety, and stress were
      measured using the Depression Anxiety Stress Scales. RESULTS: In the study
      sample, the prevalence of depression, anxiety, and stress was 18.6%, 13.1%, and
      8.7%, respectively. Young mothers and those with higher education (above
      secondary level) were more depressed (35.7% and 67.5%, respectively), anxious
      (34.9% and 68.3%, respectively), and under stress (29.7% and 62.1%, respectively)
      in their postpartum period. Postpartum working women were more stressed (60.7%)
      and anxious (51.8%), while housewives were more depressed (51.6%). Nearly half of
      the depressed mothers reported experiencing more than one stressful life event in
      their postpartum period, such as low income (41.9%; P = 0.05) or unplanned
      pregnancy (60.4%; P < 0.001). Unplanned pregnancy (OR = 1.9; P < 0.001) was the
      major significant correlate for postpartum depression, while a lack of family
      support (OR = 1.9; P < 0.001) was the major significant correlate for postpartum
      anxiety. For stress, being an older mother aged from 40 to 45 years of age (OR =
      2.0; P = 0.04) and having dissatisfaction in married life (OR = 1.9; P = 0.006)
      were the significant correlates. CONCLUSION: The study found clearly defined
      groups of women at risk for postpartum depression, anxiety, and stress. There was
      a marked association between stressful life events and postpartum depression,
      anxiety, and stress disorders.

PMID- 22654525
TI  - Sensitive and specific markers for insulin resistance, hyperandrogenemia, and
      inappropriate gonadotrophin secretion in women with polycystic ovary syndrome: a
      case-control study from Bahrain.
AB  - BACKGROUND: In women with polycystic ovary syndrome (PCOS), despite a high
      prevalence of insulin resistance, hyperandrogenemia, and disturbances in the
      secretion of gonadotrophin, the principal causes of biochemical abnormalities and
      the best endocrine markers for PCOS have not been fully identified. SUBJECTS AND
      METHODS: Serum levels of insulin, glucose, follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), total testosterone, estrogen, sex hormone-binding
      capacity (SHBG), and other related indices such as homeostasis model assessment,
      insulin glucose ratios, LH/FSH ratios, and the free androgen index (FAI) were
      determined and compared in women with PCOS (n = 50) and women without PCOS (n =
      50). RESULTS: In multivariate logistic regression analyses, among all insulin
      resistance indices, only hyperinsulinemia (odds ratio [OR] = 2.6; confidence
      interval [CI]: 1.3-5.2; P = 0.008) was significantly and independently associated
      with PCOS when adjusted for body mass index (BMI), hyperandrogenemia, and LH/FSH
      ratios. The LH/FSH ratio (OR = 5.4; CI: 1.2-23.0, P = 0.03) was the only marker
      among those indices for inappropriate gonadotrophin secretion that significantly
      and independently associated with PCOS when adjusted for BMI and
      hyperinsulinemia. Among those indices for hyperandrogenemia, FAI (OR = 1.1; CI:
      1.0-2.7; P = 0.02) and SHBG (OR = 1.2; CI: 1.2-3.4; P = 0.03) were significantly
      and independently associated with PCOS when adjusted for BMI and
      hyperinsulinemia. In addition, receiver operating characteristic analysis showed
      that the best predictive markers for PCOS were insulin (area under the curve
      [AUC] = 0.944; CI: 0.887-0.989), FAI (AUC = 0.932; CI: 0.895-0.993), SHBG (AUC =
      0.924; CI: 0.87-0.978), and LH/FSH ratios (AUC = 0.906; CI: 0.821-0.965).
      CONCLUSION: For insulin and LH/FSH ratios, FAI, and SHBG seemed the best
      predictors and markers for insulin resistance, inappropriate gonadotrophin
      secretion, and hyperandrogenemia, respectively, with high sensitivity and
      specificity for identifying Bahraini women with and without PCOS.

PMID- 22654526
TI  - Acute myeloid leukemia: focus on novel therapeutic strategies.
AB  - Acute myeloid leukemia (AML) is a heterogeneous disease with variable clinical
      outcomes. Cytogenetic analysis reveals which patients may have favorable risk
      disease, but 5-year survival in this category is only approximately 60%, with
      intermediate and poor risk groups faring far worse. Advances in our understanding
      of the biology of leukemia pathogenesis and prognosis have not been matched with
      clinical improvements. Unsatisfactory outcomes persist for the majority of
      patients with AML, particularly the elderly. Novel agents and treatment
      approaches are needed in the induction, post-remission and relapsed settings. The
      additions of clofarabine for relapsed or refractory disease and the
      hypomethylating agents represent recent advances. Clinical trials of FLT3
      inhibitors have yielded disappointing results to date, with ongoing
      collaborations attempting to identify the optimal role for these agents.
      Potential leukemia stem cell targeted therapies and treatments in the setting of
      minimal residual disease are also under investigation. In this review, we will
      discuss recent advances in AML treatment and novel therapeutic strategies.

PMID- 22654527
TI  - Current and emerging pharmacotherapies for primary CNS lymphoma.
AB  - Primary central nervous system lymphoma (PCNSL) constitutes a rare group of
      extranodal non-Hodgkin's lymphoma (NHL) primarily of B cell origin. It occurs in
      both immuno-competent and immune-compromised patients. High dose m ethotrexate
      (HD-MTX) based chemotherapy is the standard therapy. Chemotherapy with whole
      brain radiation therapy (WBRT) improves response rates and survival compared with
      WBRT alone. However, due to the increased risk for neurotoxicity with WBRT,
      recent studies have focused on using chemotherapy alone. Methotrexate based multi
      agent chemotherapy without WBRT is associated with similar t reatment rates and
      survival compared with regimens that include WBRT although controlled trials have
      not been performed. Because of the low incidence of this disease, it is difficult
      to conduct randomized controlled trials. In this article we have discussed about
      the past, present and emerging treatment options in patients with PCNSL.

PMID- 22654528
TI  - Yesterday, today and tomorrow.

PMID- 22654529
TI  - You can publish an editorial.

PMID- 22654530
TI  - Tuberous breast: Morphological study and overview of a borderline entity.
AB  - BACKGROUND: Tuberous breasts are widely known and described. Several surgical
      strategies have been proposed; however, few studies explain the origin or
      structural alterations of this deformity. No histological studies have been
      performed. The present article describes a morphological and histological study
      of breast tissue specimens. METHODS: Mammary specimens of 22 female and five male
      patients with tuberous breasts were histologically analyzed and compared with six
      specimens harvested from normal female breasts and from three cases of true
      'normal' gynecomastia. RESULTS: A high prevalence of one histological subtype was
      observed, with the presence of collagen fibres among few fibroblasts.
      Histochemical analysis highlighted alterations of the arrangement and of the
      quantity of collagen involving breast structures. CONCLUSIONS: Results of the
      present study suggest that collagen deposition alterations can better explain
      breast parenchyma modifications. Histological features of male subjects support
      this theory. Additionally, the observation of two cases in male homozygous twins
      suggests the role of genetic influences.

PMID- 22654531
TI  - A geometric analysis of mastectomy incisions: Optimizing intraoperative breast
      volume.
AB  - INTRODUCTION: The advent of acellular dermis-based tissue expander breast
      reconstruction has placed an increased emphasis on optimizing intraoperative
      volume. Because skin preservation is a critical determinant of intraoperative
      volume expansion, a mathematical model was developed to capture the influence of
      incision dimension on subsequent tissue expander volumes. METHODS: A mathematical
      equation was developed to calculate breast volume via integration of a
      geometrically modelled breast cross-section. The equation calculates volume
      changes associated with excised skin during the mastectomy incision by reducing
      the arc length of the cross-section. The degree of volume loss is subsequently
      calculated based on excision dimensions ranging from 35 mm to 60 mm. RESULTS: A
      quadratic relationship between breast volume and the vertical dimension of the
      mastectomy incision exists, such that incrementally larger incisions lead to a
      disproportionally greater amount of volume loss. The vertical dimension of the
      mastectomy incision - more so than the horizontal dimension - is of critical
      importance to maintain breast volume. Moreover, the predicted volume loss is more
      profound in smaller breasts and primarily occurs in areas that affect breast
      projection on ptosis. CONCLUSIONS: The present study is the first to model the
      relationship between the vertical dimensions of the mastectomy incision and
      subsequent volume loss. These geometric principles will aid in optimizing intra
      operative volume expansion during expander-based breast reconstruction.

PMID- 22654532
TI  - Does size matter? Technical considerations of a regenerative tissue matrix for
      use in reconstructive surgery.
AB  - INTRODUCTION: Acellular dermal matrices have been used with increasing frequency
      in both reconstructive and cosmetic surgery. While many studies have described
      the safety and morbidity profiles of these materials, little is known about the
      relative mechanical properties of individual sheets of allograft harvested from
      distinct donors. METHODS: Sixty-two individual sheets of an acellular dermal
      matrix from distinct lot numbers (signifying different donors of the dermis) were
      prospectively analyzed before use. Distribution of thickness according to
      manufacturer specifications in the dry state were as follows: 0.009 inches to
      0.013 inches (1 [1.6%]); 0.79 mm to 1.78 mm (3 [4.8%]); 0.79 mm to 2.03 mm (5
      [8%]); 0.8 mm to 3.3 mm (1 [1.6%]); 1.8 mm to 3.3 mm (10 [16.1%]) and 28 mm (6
      [9.7%]). The size of the matrix was recorded while dry, after hydration and
      following stretch. The percentage change in surface area was recorded for each
      lot. RESULTS: The 62 reconstructive cases included breast implant reconstruction
      (2 [3.2%]); ventral hernia repair (11 [17.7%]); abdominal closure following
      autologous tissue harvest (6 [9.6%]); autologous breast reconstruction (37
      [59.6%]); extremity wound closures (3 [4.8%]) and reinforcement of vertical
      rectus abdominis muscle closure (3 [4.8%]). The mean percentage change in the
      size of the acellular dermal matrix to the hydrated state was 58% (36 of 62;
      thickness 0.06 mm to 3.30 mm); the mean percentage change in size from dry state
      was 7.14% (range 0% to 18.7%). The mean percentage change in the size of the
      hydrated matrix to the stretched state was 25.7% (range 0.25% to 70.6%). The
      variability in elasticity among the individual sheets was significant (P<0.0005).
      CONCLUSION: The acellular dermal matrix displayed highly variable elastic
      properties among distinct donors. This may be significant in procedures in which
      symmetry is critical.

PMID- 22654533
TI  - Ganglion cyst in children: Reviewing treatment and recurrence rates.
AB  - BACKGROUND: Pediatric hand and wrist ganglia seem to have different
      epidemiological characteristics than those of adults - a majority are found on
      the volar aspect of the hands and wrists of patients younger than 10 years of
      age. OBJECTIVE: To determine the epidemiology, etiological factors, clinical
      presentation, treatment and outcome of patients with ganglion cysts at The
      Hospital for Sick Children (Toronto, Ontario). METHODS: The records of the
      pathology department at The Hospital for Sick Children were searched for all
      cases of ganglion cyst operated on between January 2000 and December 2008.
      RESULTS: Thirty-seven patients underwent treatment for symptomatic ganglion cyst.
      The mean age of the patients was 9.6 years, and there were 23 females. A mobile
      nodule was the initial presentation of the ganglion in 64% of the cases. Pain was
      the most common indication for surgical removal. Only 11.4% of patients
      experienced previous trauma. In 70% of the cases, the diagnosis was made
      clinically. The most common sites of occurrence were volar wrist (25.7%), dorsal
      wrist (22.8%) and the volar aspect of the base of the ring finger (17.1%).
      Surgical excision was the treatment of choice for 94.2% of the patients with
      symptomatic lesions. The minimum follow-up period was 12 months. Only one patient
      (2.8%) presented with recurrence in the series. CONCLUSION: Although it is
      possible that these findings might change with longer follow-up, the present data
      provide information to help guide the treatment of these cysts. Complete surgical
      removal is a very effective treatment, with low rates of recurrence.

PMID- 22654534
TI  - Nipple reconstruction using a two-step purse-string suture technique.
AB  - Formation of an aesthetic nipple areola complex with lasting projection remains a
      challenging final step in breast reconstruction. Despite the many techniques that
      have been described, no single approach has emerged as the gold standard. The
      current study presents a novel technique in nipple areola complex reconstruction.
      In a two-step fashion, the nipple and areola are reconstructed independently.
      This aims to create a lasting projection of the nipple while maintaining a
      natural contour among the nipple, the areola complex and the surrounding breast
      tissue. With more than 15 years of experience using this technique, the authors
      believe that it is a straightforward procedure and is reliable in providing
      satisfactory results to both the surgeon and the patient.

PMID- 22654535
TI  - Management of pelvic heterotopic ossification post-myocutaneous flap
      reconstruction of a sacral pressure ulcer.
AB  - Heterotopic ossification (HO) is a process whereby lamellar bone forms in the
      soft tissues surrounding a joint. The most common type of HO is traumatic
      myositis ossificans, which develops following traumatic injuries, burns or
      arthroplasty. A variety of other forms of HO also exist, such as those associated
      with central nervous system injury and systemic forms that can manifest at other
      joints simultaneously. Clinically, patients can present with decreased range of
      motion, pressure ulcers, nerve compression, swelling, pain or asymptomatically.
      Symptomatic patients are most commonly treated with surgical debridement of the
      affected heterotopic deposits.Spinal dysraphism (SD) is a term describing a wide
      range of congenital malformations of the neural tube, ranging from spina bifida
      occulta to the more severe form, myelomeningocele. The cause of SD is
      multifactorial and has been associated with chromosomal disorders, teratogenic
      exposure and folate deficiency. Many patients with SD experience neuropathy below
      the affected neurological level, making them particularly susceptible to pressure
      ulcers. If these ulcers are severe and do not respond to conservative therapy,
      they often require surgical debridement and flap reconstruction - a clinical
      scenario that rarely results in HO.The present article describes a case involving
      a patient with pelvic HO following myocutaneous flap reconstruction of a pressure
      ulcer. The patient was successfully treated with oral bisphosphonate and
      aggressive physiotherapy.

PMID- 22654536
TI  - A rare presentation of flexor digitorum profundus type V avulsion injury with
      associated intra-articular fracture: A case report.
AB  - Traumatic avulsions of the flexor digitorum profundus tendon are associated with
      young adults engaged in athletic activities such as football and rugby. The
      current report presents a case involving a 30-year-old man with traumatic
      avulsion of his flexor digitorum profundus and associated intra-articular distal
      phalangeal fracture secondary to injury during martial arts - an unusual cause of
      this injury. Increased attention to injuries acquired during this form of
      sporting activity is suggested.

PMID- 22654537
TI  - Primary cutaneous B-cell lymphoma: Role of surgery.
AB  - PURPOSE: To evaluate the role of surgery in patients diagnosed with primary
      cutaneous B-cell lymphoma (PCBCL) - a rare disease entity. The authors offer a
      rationale for the use of primary surgical excision in the treatment of isolated
      cutaneous lymphomas. METHODS: A literature review examining the use of primary
      surgical excision in the treatment of PCBCL was conducted. The lymphoma database
      at the Juravinski Cancer Centre (Hamilton, Ontario) was searched from January
      1995 to July 2008, generating a list of 4924 patients. A simulated computer
      program was subsequently designed to search for all possible PCBCLs. A
      retrospective chart review was then conducted on the new list of 1325 patients,
      identifying 25 patients diagnosed with PCBCL. RESULTS: The mean age of the 25
      patients with PCBCL was 59.9 years; nine (36%) were treated with surgery, and
      sixteen (64%) with radiation. The average follow-up period for patients was 3.6
      years. Twenty-four of the 25 patients were completely cured, with only one
      patient recurring in the radiation subgroup. There were no complications in the
      surgery subgroup. There were two local complications in the radiation subgroup
      consisting of chronic ulcerations. CONCLUSIONS: Primary surgical excision is an
      effective management option in the treatment of PCBCL, particularly the marginal
      zone and follicle centre subtypes.

PMID- 22654538
TI  - Treatment of keratoacanthoma: Is intralesional methotrexate an option?
AB  - BACKGROUND: Keratoacanthomas (KAs) are a variant of squamous cell carcinomas.
      Some KAs have shown aggressive behaviour, leading to metastasis and death.
      Surgical excision is the treatment of choice for most KA patients. Intralesional
      methotrexate (MTX) may also be a potential treatment option for KAs. OBJECTIVE:
      To evaluate intralesional MTX as a treatment modality for KA. METHODS: A
      retrospective chart review of nine patients with KAs treated with intralesional
      MTX was performed. Each patient had biopsy-proven KA. The lesion was initially
      debulked, and MTX was injected at the base. Patients were seen weekly in the
      office, and reinjected with intralesional MTX depending on the response of the
      lesion. Each patient was evaluated for their response to the intralesional MTX
      injections, the number of injections required and complications. RESULTS:
      Patients required approximately two to four intralesional injections (12.5 mg to
      25 mg per injection) before KA resolution. Eight of nine (88.9%) patients
      experienced complete resolution of their tumours. One patient experienced
      treatment failure, and underwent surgical excision of the KA. The average follow
      up period was 2.8 years, and there were no recurrences. CONCLUSION: The results
      from the present retrospective study show that intralesional MTX injection is an
      effective treatment option for KAs. The authors propose that intralesional MTX
      injection with initial debulking of the KA should be used as a first line of
      treatment when KAs present on the extremities, in cosmetically sensitive areas
      and in elderly patients with multiple comorbities.

PMID- 22654539
TI  - Giant cell reparative granuloma of the proximal phalanx: A case report and
      literature review.
AB  - The present article is a case report of a 16-year-old boy who presented with a
      benign bony tumour, which on histological analysis suggested giant cell
      reparative granuloma (GCRG), but was not corroborate by blood tests. The
      implications of this type of tumour and the correct diagnostic requirements were
      investigated. The correct identification of GCRG from other giant cell-containing
      tumours is important because the treatment modalities for these tumours
      significantly differ from one another. In most cases, histological findings are
      sufficient to identify the tumours. In most GCRG cases, curettage is usually a
      curative treatment option. However, due to high recurrence rates of GCRGs, close
      follow-up of these patients is warranted. Also, due to osteoclastic activity of
      the giant cells in GCRGs, the use of drugs such as calcitonin or bisphosphonates,
      which inhibit osteoclast differentiation and activation, may have an important
      influence on future treatments or in reducing the recurrence rate of these
      tumours.

PMID- 22654540
TI  - Unsolicited advice for newly minted paediatricians.

PMID- 22654541
TI  - Case 1: A blue infant with chocolate-coloured blood.

PMID- 22654542
TI  - Case 2: The clues were in the stools.

PMID- 22654543
TI  - Tipping the scales: A lawyer joins the health care team.

PMID- 22654544
TI  - Diarrhea-associated hemolytic uremic syndrome in southern Alberta: A long-term
      single-centre experience.
AB  - BACKGROUND: Reports of long-term incidence trends of endemic diarrhea-associated
      hemolytic uremic syndrome (D+HUS) are few and inconclusive. OBJECTIVE: To define
      and analyze the incidence and outcomes of D+HUS over a period of approximately 25
      years in a highly endemic region of southern Alberta. METHODS: Annual incidence
      rates of confirmed cases of D+HUS were compared between two 12-year periods (1980
      to 1992 and 1994 to 2006). Differences in therapies used, and some short- and
      long-term complications observed were also compared between the two periods.
      RESULTS: The absolute yearly number of D+HUS cases was highly variable. The
      comparison between the 1980 to 1992, and 1994 to 2006 periods demonstrated a
      modest 8.8% decrease in the total number of cases. The population-based average
      annual incidence rates were not significantly different between the two time
      periods (3.33 cases versus 2.58 cases per 100,000 population per year,
      respectively; P=0.30). Only supportive care measures were used in the latter
      period. A mortality rate of lower than 1% in the latter period was one of the
      lowest ever reported for a large cohort of D+HUS patients. CONCLUSION: The
      present long-term retrospective study of D+HUS in a highly endemic area
      documented a modest decrease in the absolute number of cases but no difference in
      the average annual incidence over an extended period of time.

PMID- 22654545
TI  - Socioeconomic factors and epinephrine prescription in children with peanut
      allergy.
AB  - BACKGROUND: Epinephrine autoinjectors provide life-saving therapy for individuals
      with peanut allergies.  OJECTIVE: To evaluate the association between
      socioeconomic status (SES) and epinephrine prescription among urban Canadian
      children with peanut allergy. METHODS: Population-based survey data from school
      children in grades 1 and 2 participating in the Toronto Child Health Evaluation
      Questionnaire were used. Children with peanut allergy, their epinephrine
      autoinjector prescription status and their SES were identified by parental
      report. RESULTS: Between January and April 2006, 5619 completed questionnaires
      from 231 Toronto, Ontario, schools were returned. A total of 153 (2.83%) children
      were identified as having a peanut allergy, 68.6% of whom reported being
      prescribed an epinephrine autoinjector. Children from upper-middle and high
      income homes (OR 8.35 [95% CI 2.72 to 25.61]) and with asthma (OR 4.74 [95% CI
      1.56 to 14.47]) were more likely to report having an epinephrine prescription.
      CONCLUSION: A significant health disparity exists in the prescribing pattern of
      epinephrine autoinjectors for peanut-allergic children from families of differing
      SES.

PMID- 22654546
TI  - One-on-one lifestyle coaching for managing adolescent obesity: Findings from a
      pilot, randomized controlled trial in a real-world, clinical setting.
AB  - BACKGROUND: Interventions for obese adolescents in real-world, clinical settings
      need to be evaluated because most weight management care occurs in this context.
      OBJECTIVES: To determine whether a lifestyle intervention that includes
      motivational interviewing and cognitive behavioural therapy (Health Initiatives
      Program [HIP]) leads to weight management that is superior to a similar lifestyle
      intervention (Youth Lifestyle Program [YLP]) that does not include these
      techniques; and to determine whether the HIP and YLP interventions are superior
      to a wait list control (WLC) group. METHODS: Obese adolescents were randomly
      assigned to a YLP (n=15), HIP (n=17) or WLC (n=14) group. The YLP and HIP were 16
      session, one-on-one interventions. The primary outcome was the percentage change
      of body mass index z-score. RESULTS: Completers-only analyses revealed 3.9% (YLP)
      and 6.5% (HIP) decreases in the percentage change of body mass index z-score
      compared with a 0.8% (WLC) increase (P<0.001). Levels of attrition did not differ
      among groups, but were relatively high (approximately 20% to 40%). CONCLUSION:
      Lifestyle interventions delivered in a real-world, clinical setting led to short
      term improvements in the obesity status of adolescents.

PMID- 22654547
TI  - Early childhood caries in Indigenous communities: A joint statement with the
      American Academy of Pediatrics.
AB  - The oral health of Indigenous children of Canada (First Nations, Inuit and Metis)
      and the United States (American Indian and Alaska Native) is a major child health
      issue. This is exemplified by the high prevalence of early childhood caries (ECC)
      with resulting adverse health effects, as well as high rates and costs of
      restorative and surgical treatments under general anesthesia. ECC is an
      infectious disease that is influenced by multiple factors, including
      socioeconomic determinants, and requires a combination of approaches for
      improvement. The present statement includes recommendations for oral health
      preventive and clinical care for young infants and pregnant women by primary
      health care providers, community-based health promotion initiatives, oral health
      workforce and access issues, and advocacy for community water fluoridation and
      fluoride varnish program access. Further community-based research on the
      epidemiology, prevention, management and microbiology of ECC in Indigenous
      communities would be beneficial.

PMID- 22654548
TI  - The sexual abuse of young people with a disability or chronic health condition.
AB  - For several reasons, children and youth with a disability or chronic health
      condition are at an increased risk of sexual abuse. Health care providers, along
      with parents and caregivers, need to maintain a high level of suspicion
      concerning possible sexual abuse of this population. Physicians especially need
      to advocate for policies to prevent or detect abuse in hospitals, schools and
      other institutional settings. Such policies include the thorough screening and
      monitoring of employees and volunteers; chaperoning physical examinations and
      treatment procedures; supervising outings; and ensuring an institutional culture
      that promotes patient privacy. In addition, physicians should promote patient
      self-awareness and empowerment, and provide early anticipatory guidance
      concerning sexuality, personal empowerment and abuse risks. The present document
      replaces the previous Canadian Paediatric Society position statement published in
      1997.

PMID- 22654549
TI  - Homeless youth's overwhelming health burden: A review of the literature.
AB  - Homelessness has reached epidemic proportions in Canada. Canadian children and
      adolescents are the most vulnerable because youth comprise the fastest growing
      segment of the homeless population. A systematic literature review was undertaken
      using MEDLINE, Web of Science and the Homeless Hub (www.homelesshub.ca) to
      encompass the time frame from January 1990 to June 2009. The following terms were
      used as key words: 'homelessness', 'homeless youth', 'poverty', 'street youth'
      and 'runaway'. The present review identified an intersection among education
      deficits, social service insufficiencies, and poor mental and physical health in
      homeless youth. Health care delivery to homeless youth was often nonanticipatory,
      inconsistent and perceived as discriminatory. However, street youth were
      identified as requiring health care for pregnancy, mental health concerns,
      sexually transmitted illnesses, respiratory conditions, substance abuse and a
      myriad of other illnesses. Plenty of work is still required to reduce health
      inequalities and improve the daily living conditions of Canadian youth living in
      poverty.

PMID- 22654550
TI  - Horizontal transmission of group B streptococcus in a neonatal intensive care
      unit.
AB  - The incidence of early-onset group B streptococcal (GBS) sepsis in the neonatal
      population has decreased substantially since the introduction of maternal
      intrapartum antibiotic prophylaxis and routine prenatal screening. However, these
      strategies have not reduced the incidence of late-onset GBS infections.
      Additional research pertaining to the transmission of late-onset GBS infections
      is required to develop effective preventive methods. The present report describes
      probable horizontal transmission of late-onset GBS infection among three infants
      in a neonatal intensive care unit. GBS strain confirmation was based on the
      microbiological picture, antibiogram and pulsed-field gel electrophoresis. These
      cases highlight the morbidity associated with late-onset GBS disease and the
      importance of considering horizontal transmission as an etiological factor in GBS
      infection in the newborn period. Further studies assessing horizontal
      transmission in late-onset GBS disease may improve prevention and early
      intervention.

PMID- 22654551
TI  - Effectiveness of Ozone with or without the Additional Use of Remineralizing
      Solution on Non-Cavitated Fissure Carious Lesions in Permanent Molars.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficiency of ozone alone
      and with a re-mineralizing solution following application on initial pit and
      fissure caries lesions in permanent molars. METHODS: Forty children (9-12 years)
      having non-cavitated fissure caries lesions on bilateral 40 first permanent
      mandibular molar teeth were participated in the study. Patients were randomly
      allocated to 2 experimental groups consisting of 20 subjects. In the first group,
      ozone was applied once for 40 seconds to the assigned test teeth of each pair. In
      the second group, ozone was applied once for 40 seconds to the assigned test
      teeth of each pair with the use of re-mineralizing solution. Progression or
      improvement of the caries was assessed at baseline, immediately after treatment
      and at 1-,2-,3-, and 6 month follow-up by comparing the DIAGNOdent values,
      Clinical Severity Indexes, Oral Hygiene Scores. The results were analyzed
      statistically by using the Wilcoxon-Test for dependent samples in each group.
      When comparing different test groups (control and experimental groups) the
      Friedman S test followed by the Mann-Whitney U test was used. RESULTS: A
      statistically significant difference was found between all of the control and
      experimental test lesions in each group (P<.001). However, there was no
      statistically significant difference between the ozone treated groups and those
      using the additional re-mineralizing solution (P>.001). CONCLUSIONS: Ozone
      treatment either alone or combined with a re-mineralizing solution was found to
      be effective for remineralization of initial fissure caries lesions.

PMID- 22654553
TI  - Thyroid: from genes to the disease.

PMID- 22654552
TI  - Sarcoma stem cells: do we know what we are looking for?
AB  - Sarcomas represent a heterogeneous group of cancers thought to originate from
      malignant transformation of mesenchymal cells. There is increasing evidence that
      many, if not all, sarcomas contain within them tumor-initiating, or "cancer
      stem," cells responsible for the initiation, maintenance, and potentially relapse
      and metastasis of the tumor. Various techniques have been adopted in recent years
      to identify putative sarcoma stem cell populations. The goal of this paper is to
      summarize the criteria used to identify a stem cell population, describe the more
      prominent markers and techniques used to isolate cancer stem cells in sarcomas,
      and review the evidence for the existence of cancer stem cells in sarcomas.

PMID- 22654554
TI  - Immunogenetic mechanisms leading to thyroid autoimmunity: recent advances in
      identifying susceptibility genes and regions.
AB  - The autoimmune thyroid diseases (AITD) include Graves' disease (GD) and
      Hashimoto's thyroiditis (HT), which are characterised by a breakdown in immune
      tolerance to thyroid antigens. Unravelling the genetic architecture of AITD is
      vital to better understanding of AITD pathogenesis, required to advance
      therapeutic options in both disease management and prevention. The early whole
      genome linkage and candidate gene association studies provided the first evidence
      that the HLA region and CTLA-4 represented AITD risk loci. Recent improvements
      in; high throughput genotyping technologies, collection of larger disease cohorts
      and cataloguing of genome-scale variation have facilitated genome-wide
      association studies and more thorough screening of candidate gene regions. This
      has allowed identification of many novel AITD risk genes and more detailed
      association mapping. The growing number of confirmed AITD susceptibility loci,
      implicates a number of putative disease mechanisms most of which are tightly
      linked with aspects of immune system function. The unprecedented advances in
      genetic study will allow future studies to identify further novel disease risk
      genes and to identify aetiological variants within specific gene regions, which
      will undoubtedly lead to a better understanding of AITD patho-physiology.

PMID- 22654556
TI  - Graves' ophthalmopathy: a review of immunogenetics.
AB  - Graves' disease (GD) is the most common cause of thyrotoxicosis and often
      involves the orbits. Graves' ophthalmopathy (GO), also known as Thyroid Eye
      Disease (TED), can be clinically significant and advance to sight-threatening
      stages. Our knowledge of the immunogenetic pathophysiology of GO is rapidly
      expanding. The present review is an attempt to summarize the current state of
      knowledge on the immunogenetics of GO. First we briefly review the epidemiology
      and clinical importance of GO, and then we describe in detail the macromolecular
      pathogenesis and finally immunogenetics of GO. Discrepancies between the results
      from various reports and the limitations of the available data are discussed. In
      particular, there is a scarcity of data from non-Asian populations. While several
      studies have demonstrated significant associations between polymorphisms in
      certain genes (especially CTLA-4, HLA-DRB-1, and TNF-alpha), there is a need for
      studies that investigate the relationship between polymorphisms and both serum
      and local concentrations of the resulting proteins. A complete understanding of
      GO susceptibility and pathogenesis has not been yet possible due to a number of
      important knowledge gaps that need to be filled by future research.

PMID- 22654558
TI  - Employing genetic markers to improve diagnosis of thyroid tumor fine needle
      biopsy.
AB  - Fine-Needle Aspiration (FNA) is the most widely used and cost-effective
      preoperative test for the initial evaluation of a thyroid nodule, although it has
      limited diagnostic accuracy for several types of tumors. Patients will often
      receive cytological report of indeterminate cytology and are referred to surgery
      for a more accurate diagnosis. An improved test would help physicians rapidly
      focus treatment on true malignancies and avoid some unnecessary treatment of
      benign tumors. This review will discuss current molecular markers that may
      improve thyroid nodule diagnosis.

PMID- 22654555
TI  - The genetic basis of graves' disease.
AB  - The presented comprehensive review of current knowledge about genetic factors
      predisposing to Graves' disease (GD) put emphasis on functional significance of
      observed associations. In particular, we discuss recent efforts aimed at refining
      diseases associations found within the HLA complex and implicating HLA class I as
      well as HLA-DPB1 loci. We summarize data regarding non-HLA genes such as PTPN22,
      CTLA4, CD40, TSHR and TG which have been extensively studied in respect to their
      role in GD. We review recent findings implicating variants of FCRL3 (gene for FC
      receptor-like-3 protein), SCGB3A2 (gene for secretory uteroglobin-related protein
      1- UGRP1) as well as other unverified possible candidate genes for GD selected
      through their documented association with type 1 diabetes mellitus: Tenr-IL2
      IL21, CAPSL (encoding calcyphosine-like protein), IFIH1(gene for interferon
      induced helicase C domain 1), AFF3, CD226 and PTPN2. We also review reports on
      association of skewed X chromosome inactivation and fetal microchimerism with GD.
      Finally we discuss issues of genotype-phenotype correlations in GD.

PMID- 22654557
TI  - Hashimoto's Thyroiditis: From Genes to the Disease.
AB  - Hashimoto's thyroiditis (HT) is the most prevalent autoimmune thyroid disorder.
      Intrathyroidal lymphocytic infiltration is followed by a gradual destruction of
      the thyroid gland which may lead to subclinical or overt hypothyroidism.
      Biochemical markers of the disease are thyroid peroxidase and/or thyroglobulin
      autoantibodies in the serum which are present with a higher prevalence in females
      than in males and increase with age. Although exact mechanisms of aetiology and
      pathogenesis of the disorder are not completely understood, a strong genetic
      susceptibility to the disease has been confirmed predominantly by family and twin
      studies. Several genes were shown to be associated with the disease occurrence,
      progression, and severity. Genes for human leukocyte antigen, cytotoxic T
      lymphocyte antigen-4, protein tyrosine phosphatase nonreceptor-type 22,
      thyroglobulin, vitamin D receptor, and cytokines are considered to be of utmost
      importance. Amongst endogenous factors for the disease development, the attention
      is focused predominantly on female sex, pregnancy with postpartum period and
      fetal microchimerism. Environmental factors influencing HT development are iodine
      intake, drugs, infections and different chemicals. Disturbed self-tolerance
      accompanied by the increased antigen presentation is a prerequisite for the HT
      occurrence, whereas proper interaction of thyroid cells, antigen presenting
      cells, and T cells are necessary for the initiation of thyroid autoimmunity.
      Secreted cytokines lead predominantly to T-helper type 1 (Th1) response as well
      as to Th 17 response which has only recently been implicated. Final outcome of HT
      is thyroid destruction which is mostly a consequence of the apoptotic processes
      combined with T-cell mediated cytotoxicity.

PMID- 22654559
TI  - Diagnostic and prognostic markers in differentiated thyroid cancer.
AB  - The MAPK/ERK (mitogen-activated protein kinase/extracellular signal- regulated
      kinase signaling pathway) and PI3K/Akt (lipid kinase phoshoinositide-3-kinase
      signaling pathway) play an important role in transmission of cell signals through
      transduction systems as ligands, transmembrane receptors and cytoplasmic
      secondary messengers to cell nucleus, where they influence the expression of
      genes that regulate important cellular processes: cell growth, proliferation and
      apoptosis. The genes, coding the signaling cascade proteins (RET, RAS, BRAF,
      PI3K, PTEN, AKT), are mutated or aberrantly expressed in thyroid cancer derived
      from follicular thyroid cell. Genetic and epigenetic alternations, concerning
      MAPK/ERK and PI3K/Akt signaling pathways, contribute to their activation and
      interaction in consequence of malignant follicular cell transformation. Moreover,
      it is additionally pointed out that genetic, as well as epigenetic DNA changing
      via aberrant methylation of several tumor suppressor and thyroid-specific genes
      is associated with tumor aggressiveness, being a jointly responsible mechanism
      for thyroid tumorigenesis. In the present manuscript the currently developed
      diagnostic and prognostic genetic/epigenetic markers are presented; the
      understanding of this molecular mechanism provides access to novel molecular
      therapeutic strategies.

PMID- 22654560
TI  - Genetic alterations in poorly differentiated and undifferentiated thyroid
      carcinomas.
AB  - Thyroid gland presents a wide spectrum of tumours derived from follicular cells
      that range from well differentiated, papillary and follicular carcinoma (PTC and
      FTC, respectively), usually carrying a good prognosis, to the clinically
      aggressive, poorly differentiated (PDTC) and undifferentiated thyroid carcinoma
      (UTC).It is usually accepted that PDTC and UTC occur either de novo or progress
      from a pre-existing well differentiated carcinoma through a multistep process of
      genetic and epigenetic changes that lead to clonal expansion and neoplastic
      development. Mutations and epigenetic alterations in PDTC and UTC are far from
      being totally clarified. Assuming that PDTC and UTC may derive from well
      differentiated thyroid carcinomas (WDTC), it is expected that some PDTC and UTC
      would harbour genetic alterations that are typical of PTC and FTC. This is the
      case for some molecular markers (BRAF and NRAS) that are present in WDTC, PDTC
      and UTC. Other genes, namely P53, are almost exclusively detected in less
      differentiated and undifferentiated thyroid tumours, supporting a diagnosis of
      PDTC or, much more often, UTC. Thyroid-specific rearrangements RET/PTC and
      PAX8/PPARgamma, on the other hand, are rarely found in PDTC and UTC, suggesting
      that these genetic alterations do not predispose cells to dedifferentiation. In
      the present review we have summarized the molecular changes associated with the
      two most aggressive types of thyroid cancer.

PMID- 22654561
TI  - Genetic alterations in medullary thyroid cancer: diagnostic and prognostic
      markers.
AB  - Medullary thyroid carcinoma (MTC) is a rare calcitonin producing neuroendocrine
      tumour that originates from the parafollicular C-cells of the thyroid gland. The
      RET proto-oncogene encodes the RET receptor tyrosine kinase, with consequently
      essential roles in cell survival, differentiation and proliferation. Somatic or
      germline mutations of the RET gene play an important role in this neoplasm in
      development of sporadic and familial forms, respectively. Genetic diagnosis has
      an important role in differentiating sporadic from familiar MTC. Furthermore,
      depending on the location of the mutation, patients can be classified into risk
      classes. Therefore, genetic screening of the RET gene plays a critical role not
      only in diagnosis but also in assessing the prognosis and course of MTC.

PMID- 22654562
TI  - New targeted therapies for thyroid cancer.
AB  - The increasing incidence of thyroid cancer is associated with a higher number of
      advanced disease characterized by the loss of cancer differentiation and
      metastatic spread. The knowledge of the molecular pathways involved in the
      pathogenesis of thyroid cancer has made possible the development of new
      therapeutic drugs able to blockade the oncogenic kinases (BRAF V600E, RET/PTC) or
      signaling kinases [vascular endothelial growth factor receptor (VEGFR), platelet
      derived growth factor receptors (PDGFR)] involved in cellular growth and
      proliferation. Some clinical trials have been conducted showing the ability of
      targeted therapies (sorafenib, sunitinib, axitinib, imanitib, vandetanib,
      pazopanib, gefitinib) in stabilizing the course of the disease. Until now,
      however, no consensus guidelines have been established for patient selection and
      more data on toxicities and side effects are needed to be collected.

PMID- 22654563
TI  - Novel cardiolipins from uncultured methane-metabolizing archaea.
AB  - Novel cardiolipins from Archaea were detected by screening the intact polar lipid
      (IPL) composition of microbial communities associated with methane seepage in
      deep-sea sediments from the Pakistan margin by high-performance liquid
      chromatography electrospray ionization mass spectrometry. A series of tentatively
      identified cardiolipin analogues (dimeric phospholipids or
      bisphosphatidylglycerol, BPG) represented 0.5% to 5% of total archaeal IPLs.
      These molecules are similar to the recently described cardiolipin analogues with
      four phytanyl chains from extreme halophilic archaea. It is worth noting that
      cardiolipin analogues from the seep archaeal communities are composed of four
      isoprenoidal chains, which may contain differences in chain length (20 and 25
      carbon atoms) and degrees of unsaturation and the presence of a hydroxyl group.
      Two novel diether lipids, structurally related to the BPGs, are described and
      interpreted as degradation products of archaeal cardiolipin analogues. Since
      archaeal communities in seep sediments are dominated by anaerobic methanotrophs,
      our observations have implications for characterizing structural components of
      archaeal membranes, in which BPGs are presumed to contribute to modulation of
      cell permeability properties. Whether BPGs facilitate interspecies interaction in
      syntrophic methanotrophic consortia remains to be tested.

PMID- 22654564
TI  - David e. Beck, m.d.

PMID- 22654565
TI  - Career development.

PMID- 22654566
TI  - Applying for a fellowship in colon and rectal surgery.
AB  - Colon and Rectal Surgery is a challenging and fulfilling field with interesting
      and widely variable tasks, making it the preferred career for an increasing
      number of residents who are in the final path of their general surgery training.
      Due to the steadily rising interest in the field, it has become increasingly
      difficult to match into a fellowship in Colon and Rectal Surgery. For those who
      have decided to pursue a career in Colon and Rectal Surgery, this overview may be
      of some use during the quite cumbersome and costly process of applying for a
      fellowship.

PMID- 22654567
TI  - Career options in colon and rectal surgery.
AB  - As Colon and Rectal Surgery has grown and diversified, the practice opportunities
      available have greatly expanded. The wealth of choices, may be daunting and even
      paralyzing for the new graduate or practitioner looking for a career change.
      Prior to making a decision, candidates must first make an honest assessment of
      their goals, abilities, and priorities. In this article, the authors briefly
      outline some of these challenges and help lay the groundwork for a successful
      decision process.

PMID- 22654568
TI  - Multispecialty clinic practice.
AB  - A multispecialty clinic practice is a common practice arrangement for colorectal
      surgeons. This type of practice has a variety of features, both positive and
      negative. The authors explore location, practice patterns, lifestyles,
      compensation, and academic opportunities associated with a multispecialty clinic
      practice. This information can assist younger surgeons in choosing a practice
      opportunity and guide experienced surgeons through their career progression.

PMID- 22654569
TI  - Getting started in clinical research.
AB  - Clinical research is an important part of an academic surgery practice. To be
      successful, it is important to understand the multiple regularity committees and
      organizations that impact research. The author briefly reviews these groups and
      provides guidance on how to initiate and conduct research.

PMID- 22654570
TI  - Role of professional societies in career development.
AB  - Professional medical societies serve several functions that may benefit society,
      the sponsoring medical profession, and individual members. Several professional
      societies are available for colorectal surgeons to join and participate in.
      Reasons to join include service, educational offerings, networking, and
      companionship. Participation can vary from membership to leadership. The
      advantages and costs of participation and how this may enhance a surgeon's career
      are described in this article.

PMID- 22654571
TI  - Contracts: making the transition from residency to work, work for you.
AB  - Residents completing colon and rectal surgery training should take seriously the
      terms of contracts offered to them. Contracts should specify how and how much
      salary will be paid, what benefits the surgeon will receive, and what services
      are to be provided. However, contracts frequently fail to disclose what costs the
      surgeon will have to cover that will lower that salary, what hours the surgeon
      must keep, and what time off the surgeon may expect. Signing a contract is easily
      done, but getting out of a contract to take a better job or move to another
      community may be difficult because of the wording in the contact. Surgeons need
      to have professional help to determine whether to sign a contract and what that
      contract should provide. An attorney experienced in representing physicians can
      be recommended by the physician's medical association.

PMID- 22654572
TI  - Retirement: when, why, and how?
AB  - Retirement from a career in Colon and Rectal Surgery is usually a personal
      decision. The details of when, why, and how are individually specific and are
      shaped by life experience, desires, personal and family commitments, as well as
      financial considerations.

PMID- 22654573
TI  - Pathologic response of primary rectal cancer to oxaliplatin-based chemotherapy.
AB  - Management of stage IV rectal cancer is controversial, and different strategies
      may be useful. Preoperative chemotherapy for liver metastases might cause
      pathologic changes over the primary rectal tumor. In this study, the authors show
      the pathologic regression of the primary rectal tumor after neoadjuvant
      chemotherapy treatment. Patients suffering stage IV rectal cancer underwent
      surgery after oxaliplatin-based chemotherapy. Age, gender, type of surgery,
      carcinoembryogenic antigen (CEA) level, presence of metastatic disease in one or
      multiple organs, ypT, ypN, and circumferential resection margin (CRM) were
      evaluated. Pathologic response of the primary tumor was estimated by using three
      conventional grading systems and a semiquantitative system assessed by the amount
      of viable cells out of the total tumor area macroscopically described. Fibrosis,
      necrosis, and colloid response were evaluated with a semiquantitative system. A
      complete pathologic response (ypTO) was found in one patient. A good response was
      observed in the 41.6% of the cases with all grading systems. Presence of fibrosis
      in the primary tumor was found in six cases. No patient showed CRM involvement.
      One patient developed a local recurrence. Oxaliplatin-based chemotherapy for
      stage IV rectal cancer provides high rates of pathologic regression in the rectal
      tumor and may allow surgery without CRM involvement.

PMID- 22654574
TI  - Approach to the Adult Kidney Stone Former.
AB  - Nephrolithiasis is a prevalent and costly condition with high recurrence rate. A
      medical evaluation to identify abnormalities responsible for nephrolithiasis and
      guide subsequent therapy has been advocated to reduce the risk of stone
      recurrence. The evaluation of kidney stone formers generally comprises an
      extensive medical history to identify metabolic, environmental, dietary and/or
      genetic factors contributing to stone formation. Imaging studies are utilized to
      evaluate and follow stone burden. Laboratory studies including stone composition
      analysis and serum and urinary chemistries are commonly obtained to further
      assess for any underlying systemic disorders, to detect environmental and
      metabolic processes contributing to stone disease, and to guide initial and
      follow-up dietary and pharmacological therapy. The nature and extent of such an
      evaluation is discussed in this review article.

PMID- 22654575
TI  - Cognitive competence as a positive youth development construct: a conceptual
      review.
AB  - This paper focuses on discussing critical thinking and creative thinking as the
      core cognitive competence. It reviews and compares several theories of thinking,
      highlights the features of critical thinking and creative thinking, and
      delineates their interrelationships. It discusses cognitive competence as a
      positive youth development construct by linking its relationships with adolescent
      development and its contributions to adolescents' learning and wellbeing.
      Critical thinking and creative thinking are translated into self-regulated
      cognitive skills for adolescents to master and capitalize on, so as to facilitate
      knowledge construction, task completion, problem solving, and decision making.
      Ways of fostering these thinking skills, cognitive competence, and ultimately
      positive youth development are discussed.

PMID- 22654576
TI  - The effects of low-level laser therapy, 670 nm, on epiphyseal growth in rats.
AB  - The longitudinal growth of long bones is attributed to epiphyseal growth.
      However, the effects of low-level laser therapy (LLLT) in such structures has
      still not been studied extensively in the literature. Therefore, the aim of this
      study was to evaluate the use of LLLT, 670 nm, at three different doses on the
      epiphyseal growth of the right tibia of rats. Twenty-one Wistar rats, aged four
      weeks, were subjected to the application of LLLT, with dosage according to the
      group (G4: were submitted to the application of 4 J/cm(2); G8: were submitted to
      the application of 8 J/cm(2); G16: were submitted to the application of 16
      J/cm(2)). After completion of protocol they were kept until they were 14 weeks of
      age and then submitted to a radiological examination (evaluation of limb length)
      and euthanised. The histological analysis of the growth plates (total thickness
      and hypertrophic and proliferative zones) was then performed. Comparisons were
      made with the untreated left tibia. No differences were observed in any of the
      reviews (radiological and histological), when comparing the right sides (treated)
      to the left (untreated). It was concluded that the treatment with LLLT within the
      parameters used caused changes neither in areas of the epiphyseal cartilage nor
      in the final length of limbs.

PMID- 22654577
TI  - Role of hemoglobin and serum iron in oral submucous fibrosis: a clinical study.
AB  - BACKGROUND: Oral submucous fibrosis is a chronic, insidious oral mucosal
      condition affecting the most parts of the oral cavity with high malignant
      transformation rate triggered by areca nut chewing, nutritional deficiencies,
      immunologic processes, and genetic predisposition. OSF causes significant
      hematological abnormalities resulting in anemia and a decrease in serum iron
      levels. AIM: The aim of this study was to estimate the hemoglobin and serum iron
      levels among patients with oral submucous fibrosis and to compare the values with
      healthy subjects. MATERIALS AND METHODS: In this hospital-based study 30
      diagnosed patients of OSMF and 15 healthy individuals were included, and the
      values of hemoglobin and serum iron levels were estimated using Sahli's and
      Ferrene methods. RESULTS: OSMF patients showed significantly lower levels of
      hemoglobin and serum iron when compared with the healthy subjects. CONCLUSION:
      The findings of the study emphasizes on the assessment of hemoglobin and serum
      iron for patients with oral submucous fibrosis. Also iron therapy should be
      instituted concomitantly with the initial diagnosis which helps to cease the
      further progression of the condition. Further extensive studies are indicated to
      understand the correlation between OSMF and iron deficiency.

PMID- 22654578
TI  - Microbial transformations of 7-hydroxyflavanone.
AB  - Microbial transformations of racemic 7-hydroxyflavanone using strains of genus
      Aspergillus (A. niger KB, A. niger 13/5, A. ochraceus 456) and the species
      Penicillium chermesinum 113 were studied. The products of O-methylation, O
      methylation along with hydroxylation at C-3' and C-4', reduction of the carbonyl
      group, reduction of the carbonyl group along with hydroxylation at C-5, and
      dehydrogenation of C-2 and C-3 were obtained. Most of the products (with the
      exception of the O-methylation one) have stronger antioxidant properties than the
      initial substrate.

PMID- 22654579
TI  - Brain perfusion MRI findings in patients with Behcet's disease.
AB  - OBJECTIVE: To search brain perfusion MRI (pMRI) changes in Behcet's disease (BD)
      with or without neurological involvement. MATERIALS AND METHOD: The pMRI were
      performed in 34 patients with BD and 16 healthy controls. Based on neurologic
      examination and post-contrast MRI, 12 patients were classified as Neuro-Behcet
      (group 1, NBD) and 22 patients as BD without neurological involvement (group 2).
      Mean transit time (MTT), time to peak (TTP), relative cerebral blood volume
      (rCBV), and relative cerebral blood flow (rCBF) were obtained and compared to
      those of healthy control group (group 3). RESULTS: There was a significant
      difference in the MTT and rCBF within the pons and parietal cortex in groups 1
      and 2. rCBV increased in cerebral pedicle in group 1 compared with groups 2 and
      3. In the temporal lobe white matter, prolonged MTT and decreased rCBF were found
      in groups 1 and 2. In the corpus striatum, internal capsule, and periventricular
      white matter, rCBF increased in group 1 compared with group 3 and decreased in
      groups 1 and 2. CONCLUSION: Brain pMRI is a very sensitive method to detect brain
      involvement in patients with BD and aids the clinical diagnosis of NBD,
      especially in patients with negative MRI findings.

PMID- 22654581
TI  - Reproductive ecology of male and female Strobili and mating system in two
      different populations of Pinus roxburghii.
AB  - We studied several flowering traits, namely, male-female cone phenology, male
      female cone production per tree, mating system, sex ratio, air-borne pollen
      grains and pollen migration, over four successive years in two different natural
      populations of P. roxburghii from Garhwal Himalaya, India. Assessment of each
      trait mentioned except pollen dispersion was done by selecting five
      representative trees randomly in each population. The pollen migration was
      studied on naturally isolated source trees. The pollen trapping was done in all
      directions up to 2.5 km. The average reproductive period in P. roxburghii was 36
      days with 3-5 days protandry. There were significant year and population effects
      for male and female cone output and pollen grains production per tree. In mass
      production year (1999), an average production of pollen cone per tree was
      estimated as 42.44 +/- 8.32 * 10(3) at lower altitude and 28.1 +/- 0.89 * 10(3)
      at higher altitude. The controlled pollination results in high level of
      outcrossing with 90% seed setting. We conclude that the high male-female ratio
      and tremendous pollen production capacity in P. roxburghii indicate high male
      competition among trees within populations. The isolation strip of 600 m is
      considered minimal for the management of seed orchard.

PMID- 22654580
TI  - Distribution of extrasynaptic NMDA receptors on neurons.
AB  - NMDA receptors are found in both synaptic and extrasynaptic locations on neurons.
      NMDA receptors also can be found on neurons in early stages prior to
      synaptogenesis, where they may be involved in migration and differentiation.
      Extrasynaptic NMDA receptors typically are associated with contacts with adjacent
      processes such as axons and glia. Extrasynaptic NMDA receptor clusters vary in
      size and may form associations with scaffolding proteins such as PSD-95 and
      SAP102. The best-characterized extrasynaptic NMDA receptors contain NR1 and NR2B
      subunits. Extrasynaptic NMDA receptors may be activated by glutamate spillover
      from synapses or from ectopic release of glutamate. Consequently, extrasynaptic
      NMDA receptor activation may occur under different circumstances than that for
      synaptic NMDA receptors, indicating different functional consequences for the
      neuron. In some cases, activation of extrasynaptic NMDA receptors may have a
      negative influence on the neuron, leading to cell damage and death, as may occur
      in some major diseases of the nervous system.

PMID- 22654582
TI  - Effects of pooling samples on the performance of classification algorithms: a
      comparative study.
AB  - A pooling design can be used as a powerful strategy to compensate for limited
      amounts of samples or high biological variation. In this paper, we perform a
      comparative study to model and quantify the effects of virtual pooling on the
      performance of the widely applied classifiers, support vector machines (SVMs),
      random forest (RF), k-nearest neighbors (k-NN), penalized logistic regression
      (PLR), and prediction analysis for microarrays (PAMs). We evaluate a variety of
      experimental designs using mock omics datasets with varying levels of pool sizes
      and considering effects from feature selection. Our results show that feature
      selection significantly improves classifier performance for non-pooled and pooled
      data. All investigated classifiers yield lower misclassification rates with
      smaller pool sizes. RF mainly outperforms other investigated algorithms, while
      accuracy levels are comparable among all the remaining ones. Guidelines are
      derived to identify an optimal pooling scheme for obtaining adequate predictive
      power and, hence, to motivate a study design that meets best experimental
      objectives and budgetary conditions, including time constraints.

PMID- 22654583
TI  - A constitutively mannose-sensitive agglutinating Salmonella enterica subsp.
      enterica serovar typhimurium strain, carrying a transposon in the fimbrial usher
      gene stbC, exhibits multidrug resistance and flagellated phenotypes.
AB  - Static broth culture favors Salmonella enterica subsp. enterica serovar
      Typhimurium to produce type 1 fimbriae, while solid agar inhibits its expression.
      A transposon inserted in stbC, which would encode an usher for Stb fimbriae of a
      non-flagellar Salmonella enterica subsp. enterica serovar Typhimurium LB5010
      strain, conferred it to agglutinate yeast cells on both cultures. RT-PCR revealed
      that the expression of the fimbrial subunit gene fimA, and fimZ, a regulatory
      gene of fimA, were both increased in the stbC mutant when grown on LB agar; fimW,
      a repressor gene of fimA, exhibited lower expression. Flagella were observed in
      the stbC mutant and this phenotype was correlated with the motile phenotype.
      Microarray data and RT-PCR indicated that the expression of three genes, motA,
      motB, and cheM, was enhanced in the stbC mutant. The stbC mutant was resistant to
      several antibiotics, consistent with the finding that expression of yhcQ and ramA
      was enhanced. A complementation test revealed that transforming a recombinant
      plasmid possessing the stbC restored the mannose-sensitive agglutination
      phenotype to the stbC mutant much as that in the parental Salmonella enterica
      subsp. enterica serovar Typhimurium LB5010 strain, indicating the possibility of
      an interplay of different fimbrial systems in coordinating their expression.

PMID- 22654584
TI  - Traditional medicinal herbs and food plants have the potential to inhibit key
      carbohydrate hydrolyzing enzymes in vitro and reduce postprandial blood glucose
      peaks in vivo.
AB  - We hypothesized that some medicinal herbs and food plants commonly used in the
      management of diabetes can reduce glucose peaks by inhibiting key carbohydrate
      hydrolyzing enzymes. To this effect, extracts of Antidesma madagascariense (AM),
      Erythroxylum macrocarpum (EM), Pittosporum senacia (PS), and Faujasiopsis
      flexuosa (FF), Momordica charantia (MC), and Ocimum tenuiflorum (OT) were
      evaluated for alpha-amylase and alpha-glucosidase inhibitory effects based on
      starch-iodine colour changes and PNP-G as substrate, respectively. Only FF and AM
      extracts/fractions were found to inhibit alpha-amylase activity significantly (P
      < 0.05) and coparable to the drug acarbose. Amylase bioassay on isolated mouse
      plasma confirmed the inhibitory potential of AM and FF extracts with the ethyl
      acetate fraction of FF being more potent (P < 0.05) than acarbose.
      Extracts/fractions of AM and MC were found to inhibit significantly (P < 0.05)
      alpha-glucosidase activity, with IC(50) comparable to the drug 1
      deoxynojirimycin. In vivo studies on glycogen-loaded mice showed significant (P <
      0.05) depressive effect on elevation of postprandial blood glucose following
      ingestion of AM and MC extracts. Our findings tend to provide a possible
      explanation for the hypoglycemic action of MC fruits and AM leaf extracts as
      alternative nutritional therapy in the management of diabetes.

PMID- 22654585
TI  - Survival after cardiac arrest and changing task profile of the cardiac arrest
      team in a tertiary care center.
AB  - BACKGROUND: The characteristics of in-hospital emergency response systems,
      survival rates, and variables associated with survival after in-hospital cardiac
      arrest vary significantly among medical centers worldwide. Aiming to optimize in
      hospital emergency response, we performed an analysis of survival after in
      hospital cardiopulmonary resuscitation and the task profile of our cardiac arrest
      team. METHODS: In-hospital emergencies handled by the cardiac arrest team in the
      years 2004 to 2006 were analyzed retrospectively, and patient and event
      characteristics were tested for their associations with survival after
      cardiopulmonary resuscitation. The results were compared to a similar prior
      analysis for the years 1995 to 1997. RESULTS: After cardiopulmonary
      resuscitation, the survival rate to discharge was 30.2% for the years 2004 to
      2006 compared to 25.1% for the years 1995 to 1997 (difference not statistically
      significant). Survival after one year was 18.5 %. An increasing percentage of
      emergency calls not corresponding to medical emergencies other than cardiac
      arrest was observed. CONCLUSIONS: The observed survival rates are considerably
      high to published data. We suggest that for further improvement of in-hospital
      emergency response systems regular training of all hospital staff members in
      immediate life support is essential. Furthermore, future training of cardiac
      arrest team members must include basic emergency response to a variety of medical
      conditions besides cardiac arrest.

PMID- 22654586
TI  - Electrochemically pretreated carbon microfiber electrodes as sensitive HPLC-EC
      detectors.
AB  - The paper focuses on the analysis and detection of electroactive compounds using
      high-performance liquid chromatography (HPLC) combined with electrochemical
      detection (EC). The fabrication and utilization of electrochemically treated
      carbon fiber microelectrodes (CFMs) as highly sensitive amperometric detectors in
      HPLC are described. The applied pretreatment procedure is beneficial for
      analytical characteristics of the sensor as demonstrated by analysis of the model
      set of phenolic acids. The combination of CFM with separation power of HPLC
      technique allows for improved detection limits due to unique electrochemical
      properties of carbon fibers. The CFM proved to be a promising tool for
      amperometric detection in liquid chromatography.

PMID- 22654587
TI  - Shesher and Welala floodplain wetlands (Lake Tana, Ethiopia): are they important
      breeding habitats for Clarias gariepinus and the migratory Labeobarbus fish
      species?
AB  - This study aims at investigating the spawning migration of the endemic
      Labeobarbus species and C. gariepinus from Lake Tana, through Ribb River, to
      Welala and Shesher wetlands. The study was conducted during peak spawning months
      (July to October, 2010). Fish were collected through overnight gillnet settings.
      A total of 1725 specimens of the genus Labeobarbus (13 species) and 506 specimens
      of C. gariepinus were collected. Six species of Labeobarbus formed prespawning
      aggregation at Ribb River mouth. However, no Labeobarbus species was found to
      spawn in the two wetlands. More than 90% of the catch in Welala and Shesher
      wetlands was contributed by C. gariepinus. This implies that these wetlands are
      ideal spawning and nursery habitats for C. gariepinus but not for the endemic
      Labeobarbus species. Except L. intermedius, all the six Labeobarbus species
      (aggregated at Ribb River mouth) and C. gariepinus (spawning at Shesher and
      Welala wetlands) were temporally segregated.

PMID- 22654588
TI  - CD8+ T cells: GITR matters.
AB  - As many members of the tumor necrosis factor receptor superfamily, glucocorticoid
      induced TNFR-related gene (GITR) plays multiple roles mostly in the cells of
      immune system. CD8(+) T cells are key players in the immunity against viruses and
      tumors, and GITR has been demonstrated to be an essential molecule for these
      cells to mount an immune response. The aim of this paper is to focus on GITR
      function in CD8(+) cells, paying particular attention to numerous and recent
      studies that suggest its crucial role in mouse disease models.

PMID- 22654589
TI  - Transcaruncular medial wall orbital decompression: an effective approach for
      patients with unilateral graves ophthalmopathy.
AB  - PURPOSE: To evaluate the reduction in proptosis, incidence of postoperative
      diplopia, and postoperative globe symmetry after transcaruncular medial wall
      decompression in patients with unilateral Graves ophthalmopathy. METHODS:
      Retrospective review of 16 consecutive patients who underwent unilateral
      transcaruncular medial wall orbital decompression from 1995 to 2007. The
      diagnosis of Graves ophthalmopathy was based on history and clinical findings
      including proptosis, lagophthalmos, lid retraction, motility restriction, and
      systemic thyroid dysfunction. RESULTS: The mean reduction in proptosis was 2.3
      mm. The mean difference in exophthalmometry preoperatively between the two eyes
      in each patient was 3.1 mm whereas postoperatively the mean difference was 1.1 mm
      (P = 0.0002). Eleven of 16 patients (69%) had 1 mm or less of asymmetry
      postoperatively. There was no statistically significant difference in the
      incidence of diplopia pre and postoperatively (P = 1.0). CONCLUSIONS: Medial wall
      orbital decompression is a safe and practical surgical approach for patients with
      unilateral Graves orbitopathy. The procedure carries a low risk of morbidity and
      yields anatomic retrusion of the globe that is comparable to other more invasive
      methods and may yield more symmetric postoperative results.

PMID- 22654590
TI  - Prevalence of metabolic syndrome in patients with psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disorder in which
      proinflammatory cytokines including IL-6 and TNF-alpha increase both locally and
      systematically. It is thought that chronic inflammation results in metabolic
      diseases and proinflammatory cytokines give rise to the development of
      atherogenesis, peripheral insulin resistance, hypertension, and type 2 diabetes.
      Our aim was to investigate the prevalence of metabolic syndrome in patients with
      psoriasis vulgaris. METHODS: Study consisted of 115 plaque-type psoriasis
      patients and 140 healthy individuals. Data including body weight, height, waist
      circumference, body-mass index, and arterial blood pressure were collected.
      Fasting blood glucose, triglyceride, and HDL levels were determined.
      International Diabetes Federation Criteria for Metabolic Syndrome and Insulin
      Resistance were used for evaluating patients with metabolic syndrome and
      diabetes. RESULTS: Compared to the control group, metabolic syndrome, diabetes
      mellitus, and hypertension were found to be higher in psoriasis patients.
      Metabolic syndrome was increased by 3-folds in psoriasis patients and was more
      prevalent in women than in men. It was determined that the prevalence of
      metabolic syndrome was higher in psoriasis patients after the age of 40.
      Metabolic syndrome was not related to smoking, severity of psoriasis, and
      duration of disease. CONCLUSIONS: Our findings suggest that psoriasis
      preconditions occurrence of a group of diseases such as diabetes mellitus,
      hypertension, and metabolic syndrome. For this reason, patients with psoriasis
      should be treated early and they should be followed with respect to metabolic
      diseases.

PMID- 22654593
TI  - Removal of Cd(II) from aquatic system using Oscillatoria sp. biosorbent.
AB  - Biosorption of Cd(II) ions from aqueous solutions by native and dried
      Oscillatoria sp. Cyanobacterium biomass was investigated in the batch mode. The
      Oscillatoria sp. was prepared from Molecular and Cell Laboratory of University of
      Mazandaran and grown in BG-11 medium. A comparison of Cd(II) adsorption
      properties of dried with native Oscillatoria sp. biomass was made, the dried one
      showed a higher biosorption capacity and faster kinetic. The influence of
      solution pH, contact time, biomass concentration, initial metal ion
      concentration, and presence of coions using dried Oscillatoria sp. biomass as
      well as pretreatment on the biosorption capacity of the biomass were studied.
      Various pretreatments of Oscillatoria sp. increased biosorption of Cd(II) at pH 7
      in comparison with native biomass. However, heating at 100  degrees C in a water
      bath showed significant improvement in Cd(II) biosorption capacity. The
      experimental biosorption data was well fitted to the Freundlich model compared to
      the Langmuir model, and the amount of Cd(II) removed from solution increased with
      increasing Cd(II) concentration. In addition, the dried biomass was investigated
      for Cd(II) removal from the simulated real sample containing about 14 mg/l Cd(II)
      at pH 7, under the same experimental condition.

PMID- 22654592
TI  - Antioxidant action of mangrove polyphenols against gastric damage induced by
      absolute ethanol and ischemia-reperfusion in the rat.
AB  - Rhizophora mangle, the red mangrove, has long been known as a traditional
      medicine. Its bark has been used as astringent, antiseptic, hemostatic, with
      antifungic and antiulcerogenic properties. In this paper, we aimed to evaluate
      the antioxidant properties of a buthanolic fraction of the R. mangle bark extract
      (RM) against experimental gastric ulcer in rats. Unib-Wh rats received
      pretreatment of R. mangle after the induction of gastric injury with absolute
      ethanol and ischemia-reperfusion. Gastric tissues from both methods were prepared
      to the enzymatic assays, the levels of sulfhydril compounds (GSH), lipid
      peroxides (LPO), and the activities of glutathione reductase (GR), glutathione
      peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) were
      measured. The RM protected the gastric mucosa in both methods used, ethanol
      induced gastric ulcer and ischemia-reperfusion, probably, by modulating the
      activities of the enzymes SOD, GPx, and GR and increasing or maintaining the
      levels of GSH; in addition, LPO levels were reduced. The results suggest that the
      RM antioxidant activity leads to tissue protection; thus one of the antiulcer
      mechanisms present on the pharmacological effects of R. mangle is the antioxidant
      property.

PMID- 22654591
TI  - LDL-apheresis: technical and clinical aspects.
AB  - The prognosis of patients suffering from severe hyperlipidemia, sometimes
      combined with elevated lipoprotein (a) levels, and coronary heart disease
      refractory to diet and lipid-lowering drugs is poor. For such patients, regular
      treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option.
      Today, there are five different LDL-apheresis systems available: cascade
      filtration or lipid filtration, immunoadsorption, heparin-induced LDL
      precipitation, dextran sulfate LDL adsorption, and the LDL hemoperfusion. There
      is a strong correlation between hyperlipidemia and atherosclerosis. Besides the
      elimination of other risk factors, in severe hyperlipidemia therapeutic
      strategies should focus on a drastic reduction of serum lipoproteins. Despite
      maximum conventional therapy with a combination of different kinds of lipid
      lowering drugs, sometimes the goal of therapy cannot be reached. Hence, in such
      patients, treatment with LDL-apheresis is indicated. Technical and clinical
      aspects of these five different LDL-apheresis methods are shown here. There were
      no significant differences with respect to or concerning all cholesterols, or
      triglycerides observed. With respect to elevated lipoprotein (a) levels, however,
      the immunoadsorption method seems to be most effective. The different published
      data clearly demonstrate that treatment with LDL-apheresis in patients suffering
      from severe hyperlipidemia refractory to maximum conservative therapy is
      effective and safe in long-term application.

PMID- 22654594
TI  - The clinical COPD questionnaire correlated with BODE index-A cross-sectional
      study.
AB  - The Global initiative for Chronic Obstructive Lung Disease (GOLD) staging has
      widely used in the stratification of the severity of COPD, while BODE (body mass
      index, airflow obstruction, dyspnea, and exercise capacity) index was proven
      superior to FEV1 in predicting mortality, exacerbation and disease severity in
      patients with COPD. Clinical COPD Questionnaire (CCQ), a questionnaire with ten
      items categorized into three domains (symptoms, functional state and mental
      state) was developed to measure health status of COPD patients. However, little
      is known about the relationship between CCQ score and BODE index. We performed a
      prospective study with the inclusion of 89 patients who were clinically stable
      after a 6-week-therapy for COPD symptoms comparing their health status assessed
      by CCQ, BODE index and GOLD staging. We found that the total CCQ score was
      correlated with BODE score (P < 0.001) and GOLD staging (P < 0.001); of three CCQ
      domains, the functional status correlated the most with BODE index (rS = 0.670)
      and GOLD staging (rS = 0.531), followed by symptoms (rS = 0.482; rS = 0.346,
      respectively), and mental status (rS = 0.340; rS = 0.236, respectively). Our data
      suggest that CCQ is a reliable and convenient alternative tool to evaluate the
      severity of COPD.

PMID- 22654595
TI  - Model thermohaline trends in the Mediterranean Sea during the last years: a
      change with respect to the last decades?
AB  - Temperature and salinity outputs from ECCO (years 93-09) and GLORYS (years 03-09)
      models have been used to compute the thermohaline and steric sea level trends in
      the surface (0-150 m), intermediate (150 m-600 m), and deep (600 m-bottom) layers
      of the Mediterranean Sea. Some changes with respect to the second half of the
      20th century have been observed: the cooling of the upper waters of the entire
      eastern basin since 1950 seems to have vanished; the warming of WMDW historically
      reported for the second half of the last century could have reversed, although
      there is no agreement between both models at this point (trends of different sign
      are predicted); the salinification of WMDW reported for the previous decades is
      not observed in the south-westernmost area in the period 93-09, and a clear
      change from positive to negative in the steric sea level trend with respect to
      the period 93-05 is detected due to the sharp decreasing steric sea level of
      years 02-06.

PMID- 22654596
TI  - Mental health among former child soldiers and never-abducted children in northern
      Uganda.
AB  - The present study aimed to evaluate posttraumatic stress symptoms, psychological
      distress, and emotional and behavioral problems in former Ugandan child soldiers
      in comparison with civilian children living in the same conflict setting.
      Participants included 133 former child soldiers and 101 never-abducted children
      in northern Uganda, who were interviewed about exposure to traumatic war-related
      experiences, posttraumatic stress symptoms, psychological distress, and emotional
      and behavioral problems. Results indicated that former child soldiers had
      experienced significantly more war-related traumatic events than nonabducted
      children, with 39.3% of girls having been forced to engage in sexual contact.
      Total scores on measures of PTSD symptoms, psychological distress, and emotional
      and behavioral problems were significantly higher among child soldiers compared
      to their never-abducted peers. Girls reported significantly more emotional and
      behavioral difficulties than boys. In never-abducted children, more mental health
      problems were associated with experiencing physical harm, witnessing the killings
      of other people, and being forced to engage in sexual contact.

PMID- 22654597
TI  - Issues in delivering morbidity management for lymphatic filariasis elimination: a
      study in Pondicherry, South India.
AB  - Lymphatic filariasis is a vector borne parasitic disease causing long term
      disability. The Global Programme to Eliminate Lymphatic Filariasis aims to
      achieve its objective through two strategies; Mass Drug Administration (MDA) to
      interrupt transmission and Morbidity Management (MM) to manage disability for
      those already affected. MDA is going on in full swing in endemic areas; but MM is
      lagging behind. An exploratory study was conducted in Pondicherry through focus
      group discussions to find out whether there are delivery issues if any, in the MM
      programme and get suggestions from end users. The study results show that MM has
      not received the same attention as MDA and there are shortcomings in the delivery
      mechanism of the programme. The importance of these findings are discussed and
      suggestions given for improving the programme.

PMID- 22654598
TI  - Atomic mineral characteristics of Indonesian osteoporosis by high-resolution
      inductively coupled plasma mass spectrometry.
AB  - Clinical research indicates that negative calcium balance is associated with low
      bone mass, rapid bone loss, and high fracture rates. However, some studies
      revealed that not only calcium is involved in bone strengthening as risk factor
      of fracture osteoporosis. Thus, in this report, the difference of metallic and
      nonmetallic elements in osteoporosis and normal bones was studied by high
      resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). The
      influence of these elements on bone metabolic processes is also discussed.
      Inclusion criteria of bone samples consist of postmenopausal woman, trabecular
      bone fracture, normal and osteoporosis BMD value, and no history of previous
      disease. The results showed that the concentration of B, Al, S, V, Co, Mo, Te,
      Ba, La, Ni, As, and Ca/P ratio is higher in osteoporosis than normal. These
      atomic minerals have negative role to imbalance between bone resorption and bone
      formation activity. Conversely, concentrations of Na, Mg, P, K, Ca, Cr, Pd, Ag,
      Mn, Fe, Cu, Zn, Rb, Sr, Pb, and Se are lower in osteoporosis than in normal
      bones. Among these atoms, known to have important roles in bone structure, we
      found involvement of atomic mineral and calcium which are considerable to
      contribute to osteoporotic phenomena.

PMID- 22654599
TI  - Antioxidant effect of MnTE-2-PyP on lung in asthma mice model.
AB  - AIM: To investigate the effects of MnTE-2-PyP on some markers of antioxidant
      defence system in asthma mice model. MATERIAL AND METHODS: The animals were
      divided into four groups: group 1, controls; group 2, injected with ovalbumin,
      group 3, treated with MnTE-2-PyP, and group 4, treated with ovalbumin and MnTE-2
      PyP. The activities of superoxide dismutase, catalase, glutathione peroxidase and
      nonprotein sulfhydryl groups content (NPSH) were determined in lung homogenate.
      RESULTS: The activities of superoxide dismutase and catalase in group 2 decreased
      significantly as compared to control group. The decrease of the same enzymes in
      group 4 was lower and significant as compared to group 2. Changes in the
      glutathione peroxidase activity showed a similar dynamics. The NPSH groups
      content decreased in group 2. In group 4 this decrease was relatively lower as
      compared to group 2. CONCLUSIONS: The application of MnTE-2-PyP mitigated the
      effects of oxidative stress in asthma mice model.

PMID- 22654600
TI  - Allelic variation at the Rht8 locus in a 19th century wheat collection.
AB  - Wheat breeding during the 20th century has put large efforts into reducing straw
      length and increasing harvest index. In the 1920s an allele of Rht8 with dwarfing
      effects, found in the Japanese cultivar "Akakomugi," was bred into European
      cultivars and subsequently spread over the world. Rht8 has not been cloned, but
      the microsatellite marker WMS261 has been shown to be closely linked to it and is
      commonly used for genotyping Rht8. The "Akakomugi" allele is strongly associated
      with WMS261-192bp. Numerous screens of wheat cultivars with different
      geographical origin have been performed to study the spread and influence of the
      WMS261-192bp during 20th century plant breeding. However, the allelic diversity
      of WMS261 in wheat cultivars before modern plant breeding and introduction of the
      Japanese dwarfing genes is largely unknown. Here, we report a study of WMS261
      allelic diversity in a historical wheat collection from 1865 representing
      worldwide major wheats at the time. The majority carried the previously reported
      164 bp or 174 bp allele, but with little geographical correlation. In a few
      lines, a rare 182 bp fragment was found. Although straw length was recognized as
      an important character already in the 19th century, Rht8 probably played a minor
      role for height variation. The use of WMS261 and other functional markers for
      analyses of historical specimens and characterization of historic crop traits is
      discussed.

PMID- 22654602
TI  - Electrochemical behavior and determination of rutin on modified carbon paste
      electrodes.
AB  - The performances of ionic liquid (1-hexyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide, IL/CPE) and iron phthalocyanine (IP/CPE)
      modified carbon paste electrodes in electroanalytical determinations of rutin
      were evaluated and compared to the performance of unmodified carbon paste
      electrode (CPE). Cyclic voltammetry (CV), differential pulse voltammetry (DPV),
      differential pulse adsorptive stripping voltammetry (DPAdSV), and amperometry
      were used for rutin analysis. The best current responses of rutin were obtained
      at pH 4.0 for all tested techniques. IL/CPE electrode was found to perform best
      with DPAdSV technique, where a detection limit (LOD) as low as 5 nmol L(-1) of
      rutin was found. On the other hand, IP/CPE showed itself to be an optimum choice
      for DPV technique, where LOD of 80 nmol L(-1) was obtained. Analytical
      applicability of newly prepared electrodes was demonstrated on determination of
      rutin in the model samples and the extracts of buckwheat seeds. To find an
      optimum method for buckwheat seeds extraction, a boiling water extraction (BWE),
      Soxhlet extraction (SE), pressurized solvent extraction (PSE), and supercritical
      fluid extraction (SFE) were tested.

PMID- 22654601
TI  - Altered expression of cellular Bcl-2 in the progression of hamster
      cholangiocarcinogenesis.
AB  - Bcl-2 is an intracytoplasmic and membrane-associated apoptosis suppressor, and
      its overexpression is closely associated with survival of malignant tumors, in
      particular their aggressive behavior and poor prognosis. The role of Bcl-2 is,
      however, still controversial in cholangiocarcinogenesis because of the
      discrepancies in the expression of the protein. In the present study, alteration
      in the expression of Bcl-2 in cholangiocarcinogenesis was investigated by
      studying the immunoreactivities of this protein in normal, hyperplastic bile
      ducts with or without dysplastic changes, and neoplastic bile duct cells from a
      hamster cholangiocarcinoma (ChC) model. Cytoplasmic staining, which reflects high
      Bcl-2 immunoreactivity, was negative to very weak in normal and hyperplastic bile
      ducts without dysplastic changes, while hyperplastic bile ducts with dysplasia
      indicated heterogeneously strong expression. On the other hand, most of the
      neoplastic cells of invasive cholangiocarcinomas were negative to weak as much as
      the level of normal bile ducts. The results suggest that the antiapoptotic factor
      Bcl-2 plays a limited role in the survival of highly proliferative, potentially
      dysplastic bile duct cells. However, the role of Bcl-2 in biliary cancer cells
      was not significant.

PMID- 22654603
TI  - Lack of association of childhood partial epilepsy with brain derived neurotrophic
      factor gene.
AB  - Brain-derived factor (BDNF) is a member of neurotrophin family and is localized
      and upregulated in areas implicated in epileptogenesis. Several lines of evidence
      make the BDNF gene a plausible candidate gene for predisposition to epilepsy. In
      this study, we tested that BDNF might be involved in the etiology of childhood
      PE. To assess whether BDNF gene C270T polimorphism could be implicated in
      vulnerability to PE, we conducted a case-control association analysis (112
      partial epileptic and 100 controls) in Turkish children. Epileptic children were
      divided into two groups: 1--idiopathic (n = 85) and 2--symptomathic epilepsy (n =
      27). There was no significant difference in genotypic distribution and allelic
      frequencies of the BDNF gene C270T polimorphism between the PE and control
      groups. However, the BDNF gene TT genotype was more frequently seen in the
      epileptic children (15 versus 11 patients, resp.). Interestingly, in the epilepsy
      group, both two children with TT genotype have posttraumatic epilepsy. The data
      indicate a possible association with the 270T genotype of the BDNF gene with a
      posttraumatic epilepsy. To draw any conclusion, further studies using larger
      sample sizes should be carried out in various ethnic populations in childhood
      epilepsies.

PMID- 22654604
TI  - Genetic diversity of upland rice germplasm in Malaysia based on quantitative
      traits.
AB  - Genetic diversity is prerequisite for any crop improvement program as it helps in
      the development of superior recombinants. Fifty Malaysian upland rice accessions
      were evaluated for 12 growth traits, yield and yield components. All of the
      traits were significant and highly significant among the accessions. The higher
      magnitudes of genotypic and phenotypic coefficients of variation were recorded
      for flag leaf length-to-width ratio, spikelet fertility, and days to flowering.
      High heritability along with high genetic advance was registered for yield of
      plant, days to flowering, and flag leaf length-to-width ratio suggesting
      preponderance of additive gene action in the gene expression of these characters.
      Plant height showed highly significant positive correlation with most of the
      traits. According to UPGMA cluster analysis all accessions were clustered into
      six groups. Twelve morphological traits provided around 77% of total variation
      among the accessions.

PMID- 22654605
TI  - Single-channel flow injection spectrophotometric determination of nickel using
      furildioxime in micellar solution.
AB  - A very simple, selective, and fast flow injection spectrophotometeric method is
      developed for determination of nickel using furildioxime as complexing agent.
      Micellar solution of brij-35 is employed to solubilize the sparingly soluble
      complex of Ni-furildioxime in buffered aqueous system (pH-9.00). Under optimized
      conditions, absorbance is linear from 0.02 to 10 MUg mL(-1) using 500 MUL sample
      volume and from 10 to 30 MUg mL(-1) using 50 MUL sample volume of nickel at 480
      nm, with R(2) = 0.9971 and 0.9916, respectively. The molar absorption coefficient
      and Sandell's sensitivity were 6.0 * 10(3) L mol(-1) cm(-1) and 0.01 ng cm(-2),
      respectively. The sample throughput of the method is 120 samples per hour with
      RSD of 0.01-0.2% for 0.02 to 10 MUg mL(-1) nickel (n = 5), indicating that the
      method is highly precise and reproducible. Interference from cobalt is removed by
      Nitroso R-salt-modified XAD-16. The developed method is validated by analysing
      certified reference materials and is applied to assess nickel content of
      commercially available cigarettes.

PMID- 22654606
TI  - Stabilizing agents for calibration in the determination of mercury using solid
      sampling electrothermal atomic absorption spectrometry.
AB  - Tetramethylene dithiocarbamate (TMDTC), diethyldithiocarbamate (DEDTC), and
      thiourea were investigated as stabilizing agents for calibration purposes in the
      determination of mercury using solid sampling electrothermal atomic absorption
      spectrometry (SS-ETAAS). These agents were used for complexation of mercury in
      calibration solutions and its thermal stabilization in a solid sampling platform.
      The calibration solutions had the form of methyl isobutyl ketone (MIBK) extracts
      or MIBK-methanol solutions with the TMDTC and DEDTC chelates and aqueous
      solutions with thiourea complexes. The best results were obtained for MIBK
      methanol solutions in the presence of 2.5 g L(-1) TMDTC. The surface of graphite
      platforms for solid sampling was modified with palladium or rhenium by using
      electrodeposition from a drop of solutions. The Re modifier is preferable due to
      a higher lifetime of platform coating. A new SS-ETAAS procedure using the direct
      sampling of solid samples into a platform with an Re modified graphite surface
      and the calibration against MIBK-methanol solutions in the presence of TMDTC is
      proposed for the determination of mercury content in solid environmental samples,
      such as soil and plants.

PMID- 22654607
TI  - Imaging modalities for the noninvasive assessment of fibrosis in Crohn's disease.
AB  - The development of strictures in Crohn's disease is a main cause of
      hospitalization and often represent an indication for surgery. The
      differentiation between inflammatory and fibrotic strictures is useful to
      determine the optimal treatment. Today, the availability of noninvasive methods
      to assess the presence and extension of strictures offers new tools for the
      diagnosis and follow-up of the disease. Bowel ultrasound, power doppler
      ultrasound, contrast-enhanced ultrasound, magnetic resonance imaging offer the
      additional advantage that they do not expose patients to ionizing radiation. In
      this paper we provide an update on the accuracy of these noninvasive methods for
      the diagnosis of Crohn's disease.

PMID- 22654608
TI  - Factors contributing to the utilization of adult mental health services in
      children and adolescents diagnosed with hyperkinetic disorder.
AB  - OBJECTIVES: To examine whether age of First diagnosis, gender, psychiatric
      comorbidity, and treatment modalities (pharmacotherapy or psychotherapy) at Child
      and Adolescent Mental Health Services (CAMHS) moderate the risk of Adult Mental
      Health Services (AMHS) utilization in patients diagnosed with hyperkinetic
      disorder at CAMHS. METHODS: Data were derived from the Madrid Psychiatric
      Cumulative Register Study. The target population comprised 32,183 patients who
      had 3 or more visits at CAMHS. Kaplan-Meier curves were used to assess survival
      data. A series of logistic regression analyses were performed to study the role
      of age of diagnosis, gender, psychiatric comorbidity, and treatment modalities.
      RESULTS: 7.1% of patients presented with hyperkinetic disorder at CAMHS. Compared
      to preschool children, children and adolescents first diagnosed with hyperkinetic
      disorder at CAMHS were more likely to use AMHS. Female gender and comorbidity
      with affective disorders, schizophrenia, schizotypal and delusional disorders
      increased the risk of use of AMHS. Pharmacological or combined treatment of
      hyperkinetic disorder diagnosed at CAMHS was associated with increased risk of
      use at AMHS. CONCLUSIONS: Older age of first diagnosis, female gender,
      psychiatric comorbidity, and pharmacological treatment at CAMHS are markers of
      risk for the transition from CAMHS to AMHS in patients with hyperkinetic disorder
      diagnosed at CAMHS.

PMID- 22654609
TI  - The effects of addition of mononucleotides on Sma nuc endonuclease activity.
AB  - Examination of the effects of mononucleotides on Sma nuc endonuclease originated
      from Gram negative bacterium Serratia marcescens displayed that any
      mononucleotide produced by Sma nuc during hydrolysis of DNA or RNA may regulate
      the enzyme activity affecting the RNase activity without pronounced influence on
      the activity towards DNA. The type of carbohydrate residue in mononucleotides
      does not affect the regulation. In contrast, the effects depend on the type of
      bases in nucleotides. AMP or dAMP was classified as a competitive inhibitor of
      partial type. GMP, UMP, and CMP were found to be uncompetitive inhibitors that
      suggest a specific site(s) for the nucleotide(s) binding in Sma nuc endonuclease.

PMID- 22654610
TI  - Ru (III) catalyzed oxidation of aliphatic ketones by N-bromosuccinimide in
      aqueous acetic acid: a kinetic study.
AB  - Kinetics of Ru (III) catalyzed oxidation of aliphatic ketones such as acetone,
      ethyl methyl ketone, diethyl ketone, iso-butylmethyl ketone by N-bromosuccinimide
      in the presence of Hg(II) acetate have been studied in aqueous acid medium. The
      order of [N-bromosuccinimide] was found to be zero both in catalyzed as well as
      uncatalyzed reactions. However, the order of [ketone] changed from unity to a
      fractional one in the presence of Ru (III). On the basis of kinetic features, the
      probable mechanisms are discussed and individual rate parameters evaluated.

PMID- 22654611
TI  - Spirituality as a positive youth development construct: a conceptual review.
AB  - The concept of spirituality as a positive youth development construct is reviewed
      in this paper. Both broad and narrow definitions of spirituality are examined and
      a working definition of spirituality is proposed. Regarding theories of
      spirituality, different models pertinent to spiritual development and the
      relationship between spirituality and positive youth development are highlighted.
      Different ecological factors, particularly family and peer influences, were found
      to influence spirituality. Research on the influence of spirituality on
      adolescent developmental outcomes is examined. Finally, ways to promote
      adolescent spirituality are discussed.

PMID- 22654612
TI  - Galectin-10 is released in the nasal lavage fluid of patients with aspirin
      sensitive respiratory disease.
AB  - The aim of this work was to determine the presence of galectin-10 in nasal lavage
      fluid (NLF) of patients with aspirin-sensitive respiratory disease (ASRD) before
      and after challenge with L-ASA (aspirin) by ELISA. Fifteen ASRD patients, ten
      aspirin-tolerant asthmatics (ATA), and fifteen healthy controls (HC) were
      studied. The baseline presence of Galectin-10 in PBMC was determined using real
      time PCR. Galectin-10 was evaluated in tissue of nasal polyps by western blot.
      Our results showed a lower expression in PBMC of ASRD patients than in ATA and
      healthy controls. However, a higher concentration of galectin-10 in NLF was found
      in ASRD patients before and after L-ASA challenge; western blot confirmed a high
      expression of galectin-10 in tissue from nasal polyps obtained from ASRD
      patients. Our results suggest a probable role of galectin-10 in the inflammatory
      response observed in ASRD patients; however, confirmatory studies are needed.

PMID- 22654613
TI  - Effect of irrigation to winter wheat on the radiation use efficiency and yield of
      summer maize in a double cropping system.
AB  - In north China, double cropping of winter wheat and summer maize is a widely
      adopted agricultural practice, and irrigation is required to obtain a high yield
      from winter wheat, which results in rapid aquifer depletion. In this experiment
      conducted in 2001-2002, 2002-2003, and 2004-2005, we studied the effects of
      irrigation regimes during specific winter wheat growing stage with winter wheat
      and summer maize double cropping systems; we measured soil moisture before sowing
      (SMBS), the photosynthetic active radiation (PAR) capture ratio, grain yield, and
      the radiation use efficiency (RUE) of summer maize. During the winter wheat
      growing season, irrigation was applied at the jointing, heading, or milking
      stage, respectively. The results showed that increased amounts of irrigation and
      irrigation later in the winter wheat growing season improved SMBS for summer
      maize. The PAR capture ratio significantly (LSD, P < 0.05) increased with
      increased SMBS, primarily in the 3 spikes leaves. With improved SMBS, both the
      grain yield and RUE increased in all the treatments. These results indicate that
      winter wheat should be irrigated in later stages to achieve reasonable grain
      yield for both crops.

PMID- 22654614
TI  - Standard enucleation with aluminium oxide implant (bioceramic) covered with
      patient's sclera.
AB  - PURPOSE: We describe in our study a modified standard enucleation, using sclera
      harvested from the enucleated eye to cover the prosthesis in order to insert a
      large porous implant and to reduce postoperative complication rates in a phthisis
      globe. METHODS: We perform initially a standard enucleation. The porous implant
      (Bioceramic) is then covered only partially by the patient's sclera. The implant
      is inserted in the posterior Tenon's space with the scleral covering looking at
      front. All patients were followed at least for twelve months (average followup 16
      months). RESULTS: We performed nineteen primary procedures (19 patients, 19 eyes,
      x M; x F) and secondary, to fill the orbital cavity in patients already operated
      by standard evisceration (7 patients, 7 eyes). There were no cases of implant
      extrusion. The orbital volume was well reintegrated. CONCLUSION: Our procedure
      was safe and effective. All patients had a good cosmetic result after final
      prosthetic fitting and we also achieved good prothesis mobility.

PMID- 22654615
TI  - A simple method for enema administration in one-day-old broiler chicks.
AB  - The present study aimed to describe a simple technique for enema administration
      in one-day-old broiler chicks. For this purpose we used 455 unsexed health birds
      divided into four groups submitted to three different experimental protocols: in
      the first one, we measured the total length of the large intestine in order to
      establish a secure distance for probe introduction; in the second, we evaluated
      maximum compliance of large intestine and diffusion range; finally, based on
      results obtained we tested the hypothesis in 400 birds in order to standardize
      the method. Enema solutions applied in an intrarectal manner with a stainless
      steel gavage BD-10 probe into one-day-old broiler chicks at 0.2 mL at a distance
      of 1.5 cm proved to be a reliable method.

PMID- 22654616
TI  - Determination and application of Pont's Index in Turkish population.
AB  - Disharmony between tooth size and dental arch size induces orthodontic problems.
      So, dental indices were identified by various authors. One of these is Pont who
      determined a method of prediction of the ideal dental arch width which has become
      known as Pont's Index. The purpose of this study was to assess the applicability
      of Pont's Index to a Turkish population and to compare the results with those
      obtained from studies of different ethnic subjects. The sample comprised 64 male
      subjects and 78 female subjects with age range from 14 to 15 years. Measurements
      were obtained directly from plaster casts; they included mesiodistal crown
      diameters of the four maxillary incisors, as well as interpremolar and intermolar
      maxillary arch widths as specified by Pont. Correlation coefficients determined
      between the measured arch width values and those calculated according to Pont's
      Index were low in all cases, with r values ranging from 0.02 to 0.36. It was
      concluded that Pont's Index should not be used to predetermine ideal arch width
      values in Turkish individuals.

PMID- 22654617
TI  - The effects of the melatonin treatment on the oxidative stress and apoptosis in
      diabetic eye and brain.
AB  - Oxidative stress plays an important role in the development of complications in
      diabetes mellitus. Antioxidant therapy has been thought to decrease oxidative
      stress. The objective of the present study was to explore the effects of
      melatonin (MLT) on oxidative stress in diabetic rat eye and brain tissue by using
      immunohistochemical methods. Diabetes was induced by streptozotocin, (STZ, 55
      mg/kg/i.p) in adult rats. MLT was given 10 mg/kg/i.p once a day for 2 weeks
      beginning from the sixth week. Six weeks later, rats were divided into three
      groups: control (CR), STZ-induced diabetic (STZ), and STZ-induced diabetic group
      received melatonin (STZ+MLT). Although no significant difference was observed
      with respect to antioxidant status, NOS activity tended to be higher in the
      untreated diabetic rats than in the treated rats. It was observed that MLT
      treatment improved the histopathological changes including apoptosis and
      oxidative stress in brain and eye in diabetic rat.

PMID- 22654618
TI  - Microarchitecture parameters describe bone structure and its strength better than
      BMD.
AB  - INTRODUCTION AND HYPOTHESIS: Some papers have shown that bone mineral density
      (BMD) may not be accurate in predicting fracture risk. Recently microarchitecture
      parameters have been reported to give information on bone characteristics. The
      aim of this study was to find out if the values of volume, fractal dimension, and
      bone mineral density are correlated with bone strength. METHODS: Forty-two human
      bone samples harvested during total hip replacement surgery were cut to
      cylindrical samples. The geometrical mesh of layers of bone mass obtained from
      microCT investigation and the volumes of each layer and fractal dimension were
      calculated. The finite element method was applied to calculate the compression
      force F causing epsilon = 0.8% strain. RESULTS: There were stronger correlations
      for microarchitecture parameters with strength than those for bone mineral
      density. The values of determination coefficient R(2) for mean volume and force
      were 0.88 and 0.90 for mean fractal dimension and force, while for BMD and force
      the value was 0.53. The samples with bigger mean bone volume of layers and bigger
      mean fractal dimension of layers (more complex structure) presented higher
      strength. CONCLUSION: The volumetric and fractal dimension parameters better
      describe bone structure and strength than BMD.

PMID- 22654619
TI  - Plankton microorganisms coinciding with two consecutive mass fish kills in a
      newly reconstructed lake.
AB  - Lake Karla, Greece, was dried up in 1962 and its refilling started in 2009. We
      examined the Cyanobacteria and unicellular eukaryotes found during two fish kill
      incidents, in March and April 2010, in order to detect possible causative agents.
      Both microscopic and molecular (16S/18S rRNA gene diversity) identification were
      applied. Potentially toxic Cyanobacteria included representatives of the
      Planktothrix and Anabaena groups. Known toxic eukaryotes or parasites related to
      fish kill events were Prymnesium parvum and Pfiesteria cf. piscicida, the latter
      being reported in an inland lake for the second time. Other potentially harmful
      microorganisms, for fish and other aquatic life, included representatives of
      Fungi, Mesomycetozoa, Alveolata, and Heterokontophyta (stramenopiles). In
      addition, Euglenophyta, Chlorophyta, and diatoms were represented by species
      indicative of hypertrophic conditions. The pioneers of L. Karla's plankton during
      the first months of its water refilling process included species that could cause
      the two observed fish kill events.

PMID- 22654620
TI  - Diagnostic value of breast proton magnetic resonance spectroscopy at 1.5T in
      different histopathological types.
AB  - The purpose of this study was to investigate the usefulness of quantitative
      proton magnetic resonance spectroscopy ((1)H-MRS) for characterizing breast
      lesions at 1.5T, and to evaluate the diagnostic performance of in vivo breast
      (1)H-MRS using receiver operating characteristics (ROC) analysis. 112 patients
      (99 malignant and 13 benign tumors) who were scanned with the MRI/MRS protocol
      were included in this study. Choline-containing compounds (tCho) levels were
      measured and compared with histological findings. The measured tCho levels in
      this work had range of 0.08-9.99 mmol/kg from 65 (66%) of 99 patients with
      malignant tumors. Of the 13 benign lesions, (1)H-MRS detected one as false
      positive, with tCho level of 0.66 mmol/kg. The optimal tCho level cutoff point
      that yielded the highest accuracy was found to be >0.0 mmol/kg. The resulting
      sensitivity was 66% and specificity 92% for distinguishing benign from malignant
      lesions. The tCho levels were found to be higher in invasive cancer compared to
      ductal carcinoma in situ or benign lesions, possibly associated with more
      aggressive behavior or faster cell replication in invasive cancer. Quantitative
      in vivo (1)H-MRS may provide useful information for characterizing
      histopatholoigical types in breast cancer.

PMID- 22654621
TI  - General and electrophysiological toxic effects of manganese in rats following
      subacute administration in dissolved and nanoparticle form.
AB  - In an attempt to model occupational and environmental Mn exposures and their
      possible interaction, young male Wistar rats were exposed to Mn by oral
      administration in dissolved form (MnCl(2).4H(2)O, 14.84 and 59.36 mg/kg b.w.) and
      by intratracheal application of MnO(2) nanoparticles (2.63 mg/kg b.w.). After 3
      and 6 weeks oral, or 3 weeks oral plus 3 weeks intratracheal, exposure, general
      toxicological, and electrophysiological tests were done. Body weight gain was
      significantly reduced after 6 and 3 plus 3 weeks exposure, but the effect of the
      latter on the pace of weight gain was stronger. Organ weights signalized systemic
      stress and effect on lungs. Changes in evoked electrophysiological responses
      (cortical sensory evoked potential and nerve action potential) indicated that the
      3 plus 3 weeks combined exposure caused equal or higher changes in the latency of
      these responses than 6 weeks of exposure, although the calculated summed Mn dose
      in the former case was lower. The results showed the importance of the
      physicochemical form of Mn in determining the toxic outcome, and suggested that
      neurofunctional markers of Mn action may indicate the human health effect better
      than conventional blood Mn measurement.

PMID- 22654622
TI  - Investigating the influence of anthropogenic forcing on observed mean and extreme
      sea level pressure trends over the Mediterranean Region.
AB  - We investigate whether the observed mean sea level pressure (SLP) trends over the
      Mediterranean region in the period from 1975 to 2004 are significantly consistent
      with what 17 models projected as response of SLP to anthropogenic forcing
      (greenhouse gases and sulphate aerosols, GS). Obtained results indicate that the
      observed trends in mean SLP cannot be explained by natural (internal)
      variability. Externally forced changes are detectable in all seasons, except
      spring. The large-scale component (spatial mean) of the GS signal is detectable
      in all the 17 models in winter and in 12 of the 17 models in summer. However, the
      small-scale component (spatial anomalies about the spatial mean) of GS signal is
      only detectable in winter within 11 of the 17 models. We also show that GS signal
      has a detectable influence on observed decreasing (increasing) tendency in the
      frequencies of extremely low (high) SLP days in winter and that these changes
      cannot be explained by internal climate variability. While the detection of GS
      forcing is robust in winter and summer, there are striking inconsistencies in
      autumn, where analysis points to the presence of an external forcing, which is
      not GS forcing.

PMID- 22654623
TI  - Beliefs in the future as a positive youth development construct: a conceptual
      review.
AB  - Beliefs in the future are an internalization of hope and optimism about future
      outcomes. This paper reviews and compares several theories of hope and optimism
      and highlights the features constituting beliefs in the future. This paper points
      out that beliefs in the future include a series of goal-directed thoughts and
      motivation, such as setting up valued and attainable goals, planning pathways,
      and maintaining self-confidence and mastery, so as to keep adolescents engaged in
      the pursuit of goals. This kind of personal mastery, together with sociocultural
      values, family, school, and peers are the antecedents leading to beliefs in the
      future, which is related to adolescents' well-being and positive development. In
      order to cultivate adolescents' beliefs in the future, enabling their ability to
      manipulate goal-directed thoughts and motivation and providing a supportive
      environment including their family, school, peers, and the society are
      recommended.

PMID- 22654624
TI  - Lattice Boltzmann method for evaluating hydraulic conductivity of finite array of
      spheres.
AB  - The hydraulic conductivity (K) represents an important hydrophysical parameter in
      a porous media. K direct measurements, usually demand a lot of work, are
      expensive and time consuming. Factors such as the media spatial variability,
      sample size, measurement method, and changes in the sample throughout the
      experiment directly affect K evaluations. One alternative to K measurement is
      computer simulation using the Lattice Boltzmann method (LBM), which can help to
      minimize problems such as changes in the sample structure during experimental
      measurements. This work presents K experimental and theoretical results
      (simulated) for three regular finite arrangements of spheres. Experimental
      measurements were carried out aiming at corroborating the LBM potential to
      predict K once the smallest relative deviation between experimental and simulated
      results was 1.4%.

PMID- 22654625
TI  - Quality and trace element profile of Tunisian olive oils obtained from plants
      irrigated with treated wastewater.
AB  - In the present work the use of treated wastewater (TWW) to irrigate olive plants
      was monitored. This type of water is characterized by high salinity and retains a
      substantial amount of trace elements, organic and metallic compounds that can be
      transferred into the soil and into the plants and fruits. In order to evaluate
      the impact of TWW on the overall quality of the oils, the time of contact of the
      olives with the soil has been taken into account. Multi-element data were
      obtained using ICP-MS. Nineteen elements (Li, B, Na, Mg, Al, K, Ca, Sc, Cr, Mn,
      Fe, Co, Ni, Cu, Zn, Sr, Mo, Ba and La) were submitted for statistical analysis.
      Using analysis of variance, linear discriminant analysis and principal component
      analysis it was possible to differentiate between oils produced from different
      batches of olives whose plants received different types of water. Also, the
      results showed that there was correlation between the elemental and mineral
      composition of the water used to irrigate the olive plots and the elemental and
      mineral composition of the oils.

PMID- 22654626
TI  - Independent component analysis to detect clustered microcalcification breast
      cancers.
AB  - The presence of clustered microcalcifications is one of the earliest signs in
      breast cancer detection. Although there exist many studies broaching this
      problem, most of them are nonreproducible due to the use of proprietary image
      datasets. We use a known subset of the currently largest publicly available
      mammography database, the Digital Database for Screening Mammography (DDSM), to
      develop a computer-aided detection system that outperforms the current
      reproducible studies on the same mammogram set. This proposal is mainly based on
      the use of extracted image features obtained by independent component analysis,
      but we also study the inclusion of the patient's age as a nonimage feature which
      requires no human expertise. Our system achieves an average of 2.55 false
      positives per image at a sensitivity of 81.8% and 4.45 at a sensitivity of 91.8%
      in diagnosing the BCRP_CALC_1 subset of DDSM.

PMID- 22654627
TI  - Striatal input- and rate-dependent effects of muscarinic receptors on pallidal
      firing.
AB  - The globus pallidus (GP) plays a key role in the overall basal ganglia (BG)
      activity. Despite evidence of cholinergic inputs to GP, their role in the spiking
      activity of GP neurons has not received attention. We examine the effect of local
      activation and blockade of muscarinic receptors (MRs) in the spontaneous firing
      of GP neurons both in normal and ipsilateral striatum-lesioned rats. We found
      that activation of MRs produces heterogeneous responses in both normal and
      ipsilateral striatum-lesioned rats: in normal rats the response evoked by MRs
      depends on the predrug basal firing rate; the inhibition evoked by MRs is higher
      in normal rats than in striatum-lesioned rats; the number of neurons that undergo
      inhibition is lower in striatum-lesioned rats than in normal rats. Our data
      suggest that modulation of MRs in the GP depends on the firing rate before their
      activation and on the integrity of the striato-pallidal pathway.

PMID- 22654628
TI  - Survival after locoregional treatments for hepatocellular carcinoma: a cohort
      study in real-world patients.
AB  - Evidence of relative effectiveness of local treatments for hepatocellular
      carcinoma (HCC) is scanty. We investigated, in a retrospective cohort study,
      whether surgical resection, radiofrequency ablation (RFA), percutaneous ethanol
      injection (PEI), and transarterial embolization with (TACE) or without (TAE)
      chemotherapy resulted in different survival in clinical practice. All patients
      first diagnosed with HCC and treated with any locoregional therapy from 1998 to
      2002 in twelve Italian hospitals were eligible. Overall survival (OS) was the
      unique endpoint. Three main comparisons were planned: RFA versus PEI, surgical
      resection versus RFA/PEI (combined), TACE/TAE versus RFA/PEI (combined).
      Propensity score method was used to minimize bias related to non random treatment
      assignment. Overall 425 subjects were analyzed, with 385 (91%) deaths after a
      median followup of 7.7 years. OS did not significantly differ between RFA and PEI
      (HR 1.11, 95% CI 0.79-1.57), between surgery and RFA/PEI (HR 0.95, 95% CI 0.64
      1.41) and between TACE/TAE and RFA/PEI (HR 0.88, 95% CI 0.66-1.17). 5-year OS
      probabilities were 0.14 for RFA, 0.18 for PEI, 0.27 for surgery, and 0.15 for
      TACE/TAE. No locoregional treatment for HCC was found to be more effective than
      the comparator. Adequately powered randomized clinical trials are still needed to
      definitely assess relative effectiveness of locoregional HCC treatment.

PMID- 22654629
TI  - Variability of water chemistry in Tundra Lakes, Petuniabukta Coast, Central
      Spitsbergen, Svalbard.
AB  - Samples of water from small tundra lakes located on raised marine terraces on the
      eastern coast of Petuniabukta (Ebbadalen, Central Spitsbergen) were examined to
      assess the changes in water chemistry that had occurred during the summer seasons
      of 2001-2003 and 2006. The unique environmental conditions of the study region
      include the predominance of sedimentary carbonate and sulphate rocks, low
      precipitation values, and an active permafrost layer with a maximum thickness of
      1.2 m. The average specific electric conductivity (EC) values for the three
      summer seasons in the four lakes ranged from 242 to 398 MUS cm(-1). The highest
      EC values were observed when the air temperature decreased and an ice cover
      formed (cryochemical effects). The ion composition was dominated by calcium (50.7
      to 86.6%), bicarbonates (39.5 to 86.4%), and sulphate anions. The high
      concentrations of HCO(3) (-), SO(4) (2-), and Ca(2+) ions were attributed to the
      composition of the bedrock, which mainly consists of gypsum and anhydrite. The
      average proportion of marine components in the total load found in the Ebbadalen
      tundra lake waters was estimated to be 8.1%. Precipitation supplies sulphates (as
      much as 69-81%) and chlorides (14-36%) of nonsea origin. The chief source of
      these compounds may be contamination from the town of Longyearbyen. Most ions
      originate in the crust, the active layer of permafrost, but some are atmospheric
      in origin and are either transported or generated in biochemical processes. The
      concentrations of most components tend to increase during the summer months,
      reaching a maximum during freezing and partially precipitating onto the bottom
      sediments.

PMID- 22654631
TI  - Diagnostic value of software-based image fusion of computed tomography and F18
      FDG PET scans in patients with malignant lymphoma.
AB  - AIM: The purpose of this study was to evaluate the accuracy of 2-deoxy-2
      [fluorine-18]fluoro-D-glucose (FDG) positron emission tomography (PET), computed
      tomography (CT), and software-based image fusion of both modalities in the
      imaging of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). METHODS: 77
      patients with NHL (n = 58) or HD (n = 19) underwent a FDG PET scan, a contrast
      enhanced CT, and a subsequent digital image fusion during initial staging or
      followup. 109 examinations of each modality were evaluated and compared to each
      other. Conventional staging procedures, other imaging techniques, laboratory
      screening, and follow-up data constituted the reference standard for comparison
      with image fusion. Sensitivity and specificity were calculated for CT and PET
      separately. RESULTS: Sensitivity and specificity for detecting malignant lymphoma
      were 90% and 76% for CT and 94% and 91% for PET, respectively. A lymph node
      region-based analysis (comprising 14 defined anatomical regions) revealed a
      sensitivity of 81% and a specificity of 97% for CT and 96% and 99% for FDG PET,
      respectively. Only three of 109 image fusion findings needed further evaluation
      (false positive). CONCLUSION: Digital fusion of PET and CT improves the accuracy
      of staging, restaging, and therapy monitoring in patients with malignant lymphoma
      and may reduce the need for invasive diagnostic procedures.

PMID- 22654630
TI  - Viral infection in renal transplant recipients.
AB  - Viruses are among the most common causes of opportunistic infection after
      transplantation. The risk for viral infection is a function of the specific virus
      encountered, the intensity of immune suppression used to prevent graft rejection,
      and other host factors governing susceptibility. Although cytomegalovirus is the
      most common opportunistic pathogen seen in transplant recipients, numerous other
      viruses have also affected outcomes. In some cases, preventive measures such as
      pretransplant screening, prophylactic antiviral therapy, or posttransplant viral
      monitoring may limit the impact of these infections. Recent advances in
      laboratory monitoring and antiviral therapy have improved outcomes. Studies of
      viral latency, reactivation, and the cellular effects of viral infection will
      provide clues for future strategies in prevention and treatment of viral
      infections. This paper will summarize the major viral infections seen following
      transplant and discuss strategies for prevention and management of these
      potential pathogens.

PMID- 22654632
TI  - Characterization and comparison of the 10-2 SITA-standard and fast algorithms.
AB  - PURPOSE: To compare the 10-2 SITA-standard and SITA-fast visual field programs in
      patients with glaucoma. METHODS: We enrolled 26 patients with open angle glaucoma
      with involvement of at least one paracentral location on 24-2 SITA-standard field
      test. Each subject performed 10-2 SITA-standard and SITA-fast tests. Within 2
      months this sequence of tests was repeated. RESULTS: SITA-fast was 30% shorter
      than SITA-standard (5.5 +/- 1.1 vs 7.9 +/- 1.1 minutes, P < 0.001). Mean MD was
      statistically significantly higher for SITA-standard compared with SITA-fast at
      first visit (Delta = 0.3 dB, P = 0.017) but not second visit. Inter-visit
      difference in MD or in number of depressed points was not significant for both
      programs. Bland-Altman analysis showed that clinically significant variations can
      exist in individual instances between the 2 programs and between repeat tests
      with the same program. CONCLUSIONS: The 10-2 SITA-fast algorithm is significantly
      shorter than SITA-standard. The two programs have similar long-term variability.
      Average same-visit between-program and same-program between-visit sensitivity
      results were similar for the study population, but clinically significant
      variability was observed for some individual test pairs. Group inter- and intra
      program test results may be comparable, but in the management of the individual
      patient field change should be verified by repeat testing.

PMID- 22654633
TI  - Age of first suicide attempt in men and women: an admixture analysis.
AB  - OBJECTIVES: To define different subgroups of suicide attempters according to age
      at onset of suicide attempts. METHODS: Participants were 229 suicide attempters
      (147 females; 82 males) admitted to a general hospital in Madrid, Spain. We used
      admixture analysis to determine the best-fitting model for the age at onset of
      suicide attempts separated by sex. RESULTS: The best fitted model for the age at
      onset of suicide attempts was a mixture of two gaussian distributions. Females
      showed an earlier age at onset of suicide attempts in both Gaussian distributions
      (mean +/- S.D.) (26.98 +/- 5.69 and 47.98 +/- 14.13) than males (32.77 +/- 8.11
      and 61.31 +/- 14.61). Early-onset female attempters were more likely to show
      borderline personality disorder than late-onset female attempters (OR = 11.11;
      95% CI = 2.43-50.0). CONCLUSIONS: Age at onset of suicide attempts characterizes
      different subpopulations of suicide attempters.

PMID- 22654634
TI  - Effect of aspirin on cell growth of human MG-63 osteosarcoma line.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in bone tissue
      repair treatment for their pharmacological action. The objective of this study
      was to determine the effect of aspirin, on osteoblast growth, using MG63 cell
      line as osteoblast model. MTT spectrophotometry results showed that 20, 100, and
      1000 MUM aspirin doses have an inhibitory effect on growth. Cell cycle analysis
      revealed that aspirin doses of 100 and 1000 MUM arrest the cell cycle in phase
      GO/G1. Parallel apoptosis/necrosis studies showed no changes in comparison to
      control cells after treatment with 1 or 10 MUM aspirin but a significantly
      increased percentage of cells in apoptosis at doses of 20, 100, and 1000 MUM. We
      highlight that treatment of osteoblast-like cells with 1000 MUM aspirin increased
      not only the percentage of cells in apoptosis but also the percentage of necrotic
      cells, which was not observed in aspirin treatments at lower doses.

PMID- 22654635
TI  - Leptin regulates proliferation and apoptosis in human prostate.
AB  - This paper aimed to evaluate the leptin role on the cellular proliferation and
      the expression of fibroblast growth factor 2, aromatase enzyme, and apoptotic
      genes in the human prostate tissue. METHODS: Fifteen samples of hyperplasic
      prostate tissue were divided in four symmetric parts maintained in RPMI medium
      supplemented with 10% fetal bovine serum, 1 ng/mL of gentamicin, and added with
      50 ng/mL leptin (L) or not (C). After 3 hours of incubation, gene expression was
      evaluated by real time RT-PCR. Cellular proliferation was evaluated by
      immunohistochemistry for PCNA. RESULTS: The leptin treatment led to an increase
      cellular proliferation (C = 21.8 +/- 0.5; L = 64.8 +/- 0.9; P < 0.0001) and in
      the expression of Bax (C = 0.4 +/- 0.1; L = 0.9 +/- 0.2; P < 0.05) while Bcl-2 (C
      = 19.9 +/- 5.6; L = 5.6 +/- 1.8; P < 0.05), Bcl-x (C = 0.2 +/- 0.06; L = 0.07 +/-
      0.02; P < 0.05), and aromatase expressions (C = 1.9 +/- 0.6; L = 0.4 +/- 0.1; P <
      0.04) were significantly reduced. CONCLUSION: Leptin has an important role in
      maintaining the physiological growth of the prostate since it stimulates both
      cellular proliferation and apoptosis, with the decrement in the aromatase gene
      expression.

PMID- 22654637
TI  - Morphometric analysis of nonsclerosed Glomeruli size and connective tissue
      content during the aging process.
AB  - Number of sclerotic glomeruli increases during the aging process. Consequently,
      majority of remained nonsclerosed glomeruli become hypertrophic and some of them
      sclerotic, too. The aim of this study was to quantify the size and connective
      tissue content of nonsclerosed glomeruli and to evaluate the percentage of
      hypertrophic ones in examined human cases during the aging. Material was right
      kidney's tissue of 30 cadavers obtained during routine autopsies. Cadavers were
      without previously diagnosed kidney disease, diabetes, hypertension, or any other
      systemic disease. Tissue specimens were routinely prepared for histological and
      morphometric analysis. Images of the histological slices were analyzed and
      captured under 400x magnification with digital camera. Further they were
      morphometrically and statistically analyzed with ImageJ and NCSS-PASS software.
      Multiple and linear regression of obtained morphometric parameters showed
      significant increase of glomerular connective tissue area and percentage. Cluster
      analysis showed the presence of two types of glomeruli. Second type was
      characterized with significantly larger size, connective tissue content, and
      significantly lower cellularity, in relation to the first type. Such glomeruli
      might be considered as hypertrophic. First type of glomeruli was predominant in
      younger cases, while second type of glomeruli was predominant in cases older than
      55 years.

PMID- 22654636
TI  - Biomarker identification for prostate cancer and lymph node metastasis from
      microarray data and protein interaction network using gene prioritization method.
AB  - Finding a genetic disease-related gene is not a trivial task. Therefore,
      computational methods are needed to present clues to the biomedical community to
      explore genes that are more likely to be related to a specific disease as
      biomarker. We present biomarker identification problem using gene prioritization
      method called gene prioritization from microarray data based on shortest paths,
      extended with structural and biological properties and edge flux using voting
      scheme (GP-MIDAS-VXEF). The method is based on finding relevant interactions on
      protein interaction networks, then scoring the genes using shortest paths and
      topological analysis, integrating the results using a voting scheme and a
      biological boosting. We applied two experiments, one is prostate primary and
      normal samples and the other is prostate primary tumor with and without lymph
      nodes metastasis. We used 137 truly prostate cancer genes as benchmark. In the
      first experiment, GP-MIDAS-VXEF outperforms all the other state-of-the-art
      methods in the benchmark by retrieving the truest related genes from the
      candidate set in the top 50 scores found. We applied the same technique to infer
      the significant biomarkers in prostate cancer with lymph nodes metastasis which
      is not established well.

PMID- 22654638
TI  - Ferrous versus ferric oral iron formulations for the treatment of iron
      deficiency: a clinical overview.
AB  - Iron deficiency anaemia represents a major public health problem, particularly in
      infants, young children, pregnant women, and females with heavy menses. Oral iron
      supplementation is a cheap, safe, and effective means of increasing haemoglobin
      levels and restoring iron stores to prevent and correct iron deficiency. Many
      preparations are available, varying widely in dosage, formulation (quick or
      prolonged release), and chemical state (ferrous or ferric form). The debate over
      the advantages of ferrous versus ferric formulations is ongoing. In this
      literature review, the tolerability and efficacy of ferrous versus ferric iron
      formulations are evaluated. We focused on studies comparing ferrous sulphate
      preparations with ferric iron polymaltose complex preparations, the two
      predominant forms of iron used. Current data show that slow-release ferrous
      sulphate preparations remain the established and standard treatment of iron
      deficiency, irrespective of the indication, given their good bioavailability,
      efficacy, and acceptable tolerability demonstrated in several large clinical
      studies.

PMID- 22654639
TI  - Relationship of body mass index to alcohol consumption in college freshmen.
AB  - OBJECTIVE: Assess the relationship between body mass index (BMI) and drinking in
      college freshman. METHOD: College freshman (N = 199) at a university completed
      the drinking questionnaires. Drinking amount and the alcohol problem index (RAPI)
      served as outcomes, and BMI was the independent variable. RESULTS: RAPI scores
      were associated with gender, amount of drinking, and BMI (P < 0.001, F = 13.44).
      Increase of RAPI with drinking amount was larger for females (slope = 0.06) than
      for males (slope = 0.03). CONCLUSION: This information can be helpful when
      providing health promotion strategies to college students regarding nutrition
      modifications that would be most beneficial for their health.

PMID- 22654640
TI  - Evaluation of melanogenesis in A-375 cells in the presence of DMSO and analysis
      of pyrolytic profile of isolated melanin.
AB  - The increase of a skin malignant melanoma (melanoma malignum) incidence in the
      world has been observed in recent years. The tumour, especially in advanced
      stadium with metastases, is highly resistant to conventional treatment. One of
      the strategies is to modulate melanogenesis using chemical compounds. In this
      study, the processes of differentiation and melanogenesis induced by
      dimethylsulfoxide (DMSO) in human melanoma cells (A-375) were investigated.
      Natural melanin isolated from A-375 melanoma cell line treated with 0.3% DMSO was
      analyzed by pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS) method. The
      products derived from pheomelanin have not been stated in the pyrolytic profile
      of analyzed melanin. Within all products derived from eumelanins, 1,2-benzenediol
      has been predominated. It has been shown that in the melanoma cells stimulated
      with 0.3% and 1% DMSO, the increase of transcriptional activity of the tyrosinase
      gene took place. It was accompanied by the rise of tyrosinase activity and an
      accumulation of melanin in the cells. The better knowledge about the structure of
      melanins can contribute to establish the uniform criteria of malignant melanoma
      morbidity risk.

PMID- 22654641
TI  - Effect of atmospheric pollutants on the air quality in Tunisia.
AB  - This paper presents the evolution of Saharan dust advection when the PM10
      (particles with an aerodynamic diameter below 10 MUm) concentration exceeds
      standard limits in different Tunisian sites. Meteorological and concentration
      data (from 2004 to 2010) obtained from several monitoring stations and in situ
      measurements were used to identify African dust change in seasonal occurrence,
      their source origin, and their impact on surface PM10 concentrations. We pointed
      out that the Saharan dust contribution caused frequently the surpassing of the
      maximum number of days in excess of EU standard limits as well as of the maximum
      yearly average in the Mediterranean Tunisian coasts. The maximum daily
      concentration reaches 439 MUg/m(3) during the Saharan events. The decrease in
      particulate levels recorded at the end of each event is due to the injection of
      European air masses and rainfalls. Primary pollutants peaks were much higher in
      winter than in summer which can be explained on the basis of the lower
      ventilation and mixing.

PMID- 22654642
TI  - Accumulation of aluminium and physiological status of tree foliage in the
      vicinity of a large aluminium smelter.
AB  - A pollution gradient was observed in tree foliage sampled in the vicinity of a
      large aluminium production facility in Patagonia (Argentina). Leaves of
      Eucalyptus rostrata, and Populus hybridus and different needle ages of Pinus
      spec. were collected and concentrations of aluminium (Al) and sulphur (S) as well
      as physiological parameters (chlorophyll and lipid oxidation products) were
      analyzed. Al and S concentrations indicate a steep pollution gradient in the
      study showing a relationship with the physiological parameters in particular
      membrane lipid oxidation products. The present study confirms that aluminium
      smelting results in high Al and sulphur deposition in the study area, and
      therefore further studies should be carried out taking into account potentially
      adverse effects of these compounds on human and ecosystem health.

PMID- 22654643
TI  - Algorithms and results of eye tissues differentiation based on RF ultrasound.
AB  - Algorithms and software were developed for analysis of B-scan ultrasonic signals
      acquired from commercial diagnostic ultrasound system. The algorithms process raw
      ultrasonic signals in backscattered spectrum domain, which is obtained using two
      time-frequency methods: short-time Fourier and Hilbert-Huang transformations. The
      signals from selected regions of eye tissues are characterized by parameters: B
      scan envelope amplitude, approximated spectral slope, approximated spectral
      intercept, mean instantaneous frequency, mean instantaneous bandwidth, and
      parameters of Nakagami distribution characterizing Hilbert-Huang transformation
      output. The backscattered ultrasound signal parameters characterizing intraocular
      and orbit tissues were processed by decision tree data mining algorithm. The
      pilot trial proved that applied methods are able to correctly classify signals
      from corpus vitreum blood, extraocular muscle, and orbit tissues. In 26 cases of
      ocular tissues classification, one error occurred, when tissues were classified
      into classes of corpus vitreum blood, extraocular muscle, and orbit tissue. In
      this pilot classification parameters of spectral intercept and Nakagami parameter
      for instantaneous frequencies distribution of the 1st intrinsic mode function
      were found specific for corpus vitreum blood, orbit and extraocular muscle
      tissues. We conclude that ultrasound data should be further collected in clinical
      database to establish background for decision support system for ocular tissue
      noninvasive differentiation.

PMID- 22654644
TI  - Fabrication of a porous fiber cladding material using microsphere templating for
      improved response time with fiber optic sensor arrays.
AB  - A highly porous optical-fiber cladding was developed for evanescent-wave fiber
      sensors, which contains sensor molecules, maintains guiding conditions in the
      optical fiber, and is suitable for sensing in aqueous environments. To make the
      cladding material (a poly(ethylene) glycol diacrylate (PEGDA) polymer) highly
      porous, a microsphere templating strategy was employed. The resulting pore
      network increases transport of the target analyte to the sensor molecules located
      in the cladding, which improves the sensor response time. This was demonstrated
      using fluorescein-based pH sensor molecules, which were covalently attached to
      the cladding material. Scanning electron microscopy was used to examine the
      structure of the templated polymer and the large network of interconnected pores.
      Fluorescence measurements showed a tenfold improvement in the response time for
      the templated polymer and a reliable pH response over a pH range of five to nine
      with an estimated accuracy of 0.08 pH units.

PMID- 22654645
TI  - Strength training with superimposed whole body vibration does not preferentially
      modulate cortical plasticity.
AB  - Paired-pulse transcranial magnetic stimulation (TMS) was used to investigate 4
      wks of leg strength training with and without whole body vibration (WBV) on
      corticospinal excitability and short-latency intracortical inhibition (SICI).
      Participants (n = 12) were randomly allocated to either a control or experimental
      (WBV) group. All participants completed 12 squat training sessions either with
      (WBV group) or without (control group) exposure to WBV (f = 35 Hz, A = 2.5 mm).
      There were significant (P < 0.05) increases in squat strength and corticospinal
      excitability and significant (P < 0.05) reductions in SICI for both groups
      following the 4 wk intervention. There were no differences detected between
      groups for any dependant variable (P > 0.05). It appears that WBV training does
      not augment the increase in strength or corticospinal excitability induced by
      strength training alone.

PMID- 22654646
TI  - Relationships between rainy days, mean daily intensity, and seasonal rainfall
      over the Koyna catchment during 1961-2005.
AB  - There are limitations in using monthly rainfall totals in studies of rainfall
      climatology as well as in hydrological and agricultural investigations.
      Variations in rainfall may be considered to result from frequency changes in the
      daily rainfall of the respective regime. In the present study, daily rainfall
      data of the stations inside the Koyna catchment has been analysed for the period
      of 1961-2005 to understand the relationship between the rain and rainy days, mean
      daily intensity (MDI) and seasonal rainfall over the catchment on monthly as well
      as seasonal scale. Considering the topographical location of the catchment,
      analysis of seasonal rainfall data of 8 stations suggests that a linear
      relationship fits better than the logarithmic relationship in the case of
      seasonal rainfall versus mean daily intensity. So far as seasonal rainfall versus
      number of rainy days is considered, the logarithmic relationship is found to be
      better.

PMID- 22654647
TI  - A review for solitary plasmacytoma of bone and extramedullary plasmacytoma.
AB  - Solitary plasmacytoma (SP) is characterized by a mass of neoplastic monoclonal
      plasma cells in either bone (SBP) or soft tissue without evidence of systemic
      disease attributing to myeloma. Biopsy confirmation of a monoclonal plasma cell
      infiltration from a single site is required for diagnosis. The common
      presentation of SBP is in the axial skeleton, whereas the extramedullary
      plasmacytoma (EMP) is usually seen in the head and neck. The ratio of SP seen at
      males to females is 2 : 1 and the median age of patients is 55 years. The
      incidence rate of SP in black race is approximately 30% higher than the white
      race. Incidence rate increases exponentially by advancing age. SBP has a
      significant higher risk for progression to myeloma, and the choice of treatment
      is radiotherapy (RT) that is applied with curative intent at min. 4000 cGy. By
      only RT application, long-term disease-free survival (DFS) is possible for
      approximately 30% of patients with SBP and 65% of patients with EMP.

PMID- 22654648
TI  - Immunostimulant effect of Egyptian propolis in rabbits.
AB  - The present experiment was conducted to study the effect of ethanolic extract of
      Egyptian propolis given alone or in combination with inactivated Pasteurella
      multocida vaccine on rabbits challenged with a virulent strain of Pasteurella
      multocida. Fifty-six New-Zealand rabbits, 6-8 weeks old and non-vaccinated
      against pasteurellosis, were randomly divided into eight equal groups. The first
      group was kept as a control for the experiment. The other groups received
      different treatments with propolis extract, inactivated vaccine, or both. The
      experiment continued for seven weeks during which clinical signs, body weight,
      and mortality rate were monitored, and blood samples were collected weekly for
      evaluating the leukogram, serum biochemistry, and immune response in all groups
      of animals. At the end of the seventh week, the animals were subjected to
      challenge with a virulent strain of Pasteurella multocida. Two weeks later,
      tissue specimens were collected from different organs for histopathological
      examination. Results showed that rabbits of the groups treated with both propolis
      and the vaccine by different routes appeared healthy after challenge. It has been
      concluded that alcoholic extract of propolis administrated in combination with
      inactivated Pasteurella multocida vaccine has no adverse effects on the general
      health conditions and enhances immune response in rabbits.

PMID- 22654649
TI  - Application of hyphenated techniques in speciation analysis of arsenic, antimony,
      and thallium.
AB  - Due to the fact that metals and metalloids have a strong impact on the
      environment, the methods of their determination and speciation have received
      special attention in recent years. Arsenic, antimony, and thallium are important
      examples of such toxic elements. Their speciation is especially important in the
      environmental and biomedical fields because of their toxicity, bioavailability,
      and reactivity. Recently, speciation analytics has been playing a unique role in
      the studies of biogeochemical cycles of chemical compounds, determination of
      toxicity and ecotoxicity of selected elements, quality control of food products,
      control of medicines and pharmaceutical products, technological process control,
      research on the impact of technological installation on the environment,
      examination of occupational exposure, and clinical analysis. Conventional methods
      are usually labor intensive, time consuming, and susceptible to interferences.
      The hyphenated techniques, in which separation method is coupled with
      multidimensional detectors, have become useful alternatives. The main advantages
      of those techniques consist in extremely low detection and quantification limits,
      insignificant interference, influence as well as high precision and repeatability
      of the determinations. In view of their importance, the present work overviews
      and discusses different hyphenated techniques used for arsenic, antimony, and
      thallium species analysis, in different clinical, environmental and food
      matrices.

PMID- 22654650
TI  - A real-time PCR assay for bat SARS-like coronavirus detection and its application
      to Italian greater horseshoe bat faecal sample surveys.
AB  - Bats are source of coronaviruses closely related to the severe acute respiratory
      syndrome (SARS) virus. Numerous studies have been carried out to identify new bat
      viruses related to SARS-coronavirus (bat-SARS-like CoVs) using a reverse
      transcribed-polymerase chain reaction assay. However, a qualitative PCR could
      underestimate the prevalence of infection, affecting the epidemiological
      evaluation of bats in viral ecology. In this work an SYBR Green-real time PCR
      assay was developed for diagnosing infection with SARS-related coronaviruses from
      bat guano and was applied as screening tool in a survey carried out on 45 greater
      horseshoe bats (Rhinolophus ferrumequinum) sampled in Italy in 2009. The assay
      showed high sensitivity and reproducibility. Its application on bats screening
      resulted in a prevalence of 42%. This method could be suitable as screening tool
      in epidemiological surveys about the presence of bat-SARS-like CoVs, consequently
      to obtain a more realistic scenario of the viral prevalence in the population.

PMID- 22654651
TI  - Measuring Granger causality between cortical regions from voxelwise fMRI BOLD
      signals with LASSO.
AB  - Functional brain network studies using the Blood Oxygen-Level Dependent (BOLD)
      signal from functional Magnetic Resonance Imaging (fMRI) are becoming
      increasingly prevalent in research on the neural basis of human cognition. An
      important problem in functional brain network analysis is to understand directed
      functional interactions between brain regions during cognitive performance. This
      problem has important implications for understanding top-down influences from
      frontal and parietal control regions to visual occipital cortex in visuospatial
      attention, the goal motivating the present study. A common approach to measuring
      directed functional interactions between two brain regions is to first create
      nodal signals by averaging the BOLD signals of all the voxels in each region, and
      to then measure directed functional interactions between the nodal signals.
      Another approach, that avoids averaging, is to measure directed functional
      interactions between all pairwise combinations of voxels in the two regions. Here
      we employ an alternative approach that avoids the drawbacks of both averaging and
      pairwise voxel measures. In this approach, we first use the Least Absolute
      Shrinkage Selection Operator (LASSO) to pre-select voxels for analysis, then
      compute a Multivariate Vector AutoRegressive (MVAR) model from the time series of
      the selected voxels, and finally compute summary Granger Causality (GC)
      statistics from the model to represent directed interregional interactions. We
      demonstrate the effectiveness of this approach on both simulated and empirical
      fMRI data. We also show that averaging regional BOLD activity to create a nodal
      signal may lead to biased GC estimation of directed interregional interactions.
      The approach presented here makes it feasible to compute GC between brain regions
      without the need for averaging. Our results suggest that in the analysis of
      functional brain networks, careful consideration must be given to the way that
      network nodes and edges are defined because those definitions may have important
      implications for the validity of the analysis.

PMID- 22654652
TI  - A two-dimensional model of the colonic crypt accounting for the role of the
      basement membrane and pericryptal fibroblast sheath.
AB  - The role of the basement membrane is vital in maintaining the integrity and
      structure of an epithelial layer, acting as both a mechanical support and forming
      the physical interface between epithelial cells and the surrounding connective
      tissue. The function of this membrane is explored here in the context of the
      epithelial monolayer that lines the colonic crypt, test-tube shaped invaginations
      that punctuate the lining of the intestine and coordinate a regular turnover of
      cells to replenish the epithelial layer every few days. To investigate the
      consequence of genetic mutations that perturb the system dynamics and can lead to
      colorectal cancer, it must be possible to track the emerging tissue level changes
      that arise in the crypt. To that end, a theoretical crypt model with a realistic,
      deformable geometry is required. A new discrete crypt model is presented, which
      focuses on the interaction between cell- and tissue-level behaviour, while
      incorporating key subcellular components. The model contains a novel description
      of the role of the surrounding tissue and musculature, based upon experimental
      observations of the tissue structure of the crypt, which are also reported. A two
      dimensional (2D) cross-sectional geometry is considered, and the shape of the
      crypt is allowed to evolve and deform. Simulation results reveal how the shape of
      the crypt may contribute mechanically to the asymmetric division events typically
      associated with the stem cells at the base. The model predicts that epithelial
      cell migration may arise due to feedback between cell loss at the crypt collar
      and density-dependent cell division, an hypothesis which can be investigated in a
      wet lab. This work forms the basis for investigation of the deformation of the
      crypt structure that can occur due to proliferation of cells exhibiting mutant
      phenotypes, experiments that would not be possible in vivo or in vitro.

PMID- 22654653
TI  - Optimality of human contour integration.
AB  - For processing and segmenting visual scenes, the brain is required to combine a
      multitude of features and sensory channels. It is neither known if these complex
      tasks involve optimal integration of information, nor according to which
      objectives computations might be performed. Here, we investigate if optimal
      inference can explain contour integration in human subjects. We performed
      experiments where observers detected contours of curvilinearly aligned edge
      configurations embedded into randomly oriented distractors. The key feature of
      our framework is to use a generative process for creating the contours, for which
      it is possible to derive a class of ideal detection models. This allowed us to
      compare human detection for contours with different statistical properties to the
      corresponding ideal detection models for the same stimuli. We then subjected the
      detection models to realistic constraints and required them to reproduce human
      decisions for every stimulus as well as possible. By independently varying the
      four model parameters, we identify a single detection model which quantitatively
      captures all correlations of human decision behaviour for more than 2000 stimuli
      from 42 contour ensembles with greatly varying statistical properties. This model
      reveals specific interactions between edges closely matching independent findings
      from physiology and psychophysics. These interactions imply a statistics of
      contours for which edge stimuli are indeed optimally integrated by the visual
      system, with the objective of inferring the presence of contours in cluttered
      scenes. The recurrent algorithm of our model makes testable predictions about the
      temporal dynamics of neuronal populations engaged in contour integration, and it
      suggests a strong directionality of the underlying functional anatomy.

PMID- 22654654
TI  - Conformational spread in the flagellar motor switch: a model study.
AB  - The reliable response to weak biological signals requires that they be amplified
      with fidelity. In E. coli, the flagellar motors that control swimming can switch
      direction in response to very small changes in the concentration of the signaling
      protein CheY-P, but how this works is not well understood. A recently proposed
      allosteric model based on cooperative conformational spread in a ring of
      identical protomers seems promising as it is able to qualitatively reproduce
      switching, locked state behavior and Hill coefficient values measured for the
      rotary motor. In this paper we undertook a comprehensive simulation study to
      analyze the behavior of this model in detail and made predictions on three
      experimentally observable quantities: switch time distribution, locked state
      interval distribution, Hill coefficient of the switch response. We parameterized
      the model using experimental measurements, finding excellent agreement with
      published data on motor behavior. Analysis of the simulated switching dynamics
      revealed a mechanism for chemotactic ultrasensitivity, in which cooperativity is
      indispensable for realizing both coherent switching and effective amplification.
      These results showed how cells can combine elements of analog and digital control
      to produce switches that are simultaneously sensitive and reliable.

PMID- 22654655
TI  - Identification of molecular pathologies sufficient to cause neuropathic
      excitability in primary somatosensory afferents using dynamical systems theory.
AB  - Pain caused by nerve injury (i.e. neuropathic pain) is associated with
      development of neuronal hyperexcitability at several points along the pain
      pathway. Within primary afferents, numerous injury-induced changes have been
      identified but it remains unclear which molecular changes are necessary and
      sufficient to explain cellular hyperexcitability. To investigate this, we built
      computational models that reproduce the switch from a normal spiking pattern
      characterized by a single spike at the onset of depolarization to a neuropathic
      one characterized by repetitive spiking throughout depolarization. Parameter
      changes that were sufficient to switch the spiking pattern also enabled membrane
      potential oscillations and bursting, suggesting that all three pathological
      changes are mechanistically linked. Dynamical analysis confirmed this prediction
      by showing that excitability changes co-develop when the nonlinear mechanism
      responsible for spike initiation switches from a quasi-separatrix-crossing to a
      subcritical Hopf bifurcation. This switch stems from biophysical changes that
      bias competition between oppositely directed fast- and slow-activating
      conductances operating at subthreshold potentials. Competition between activation
      and inactivation of a single conductance can be similarly biased with equivalent
      consequences for excitability. "Bias" can arise from a multitude of molecular
      changes occurring alone or in combination; in the latter case, changes can add or
      offset one another. Thus, our results identify pathological change in the
      nonlinear interaction between processes affecting spike initiation as the
      critical determinant of how simple injury-induced changes at the molecular level
      manifest complex excitability changes at the cellular level. We demonstrate that
      multiple distinct molecular changes are sufficient to produce neuropathic changes
      in excitability; however, given that nerve injury elicits numerous molecular
      changes that may be individually sufficient to alter spike initiation, our
      results argue that no single molecular change is necessary to produce neuropathic
      excitability. This deeper understanding of degenerate causal relationships has
      important implications for how we understand and treat neuropathic pain.

PMID- 22654656
TI  - Estimating the fitness cost of escape from HLA presentation in HIV-1 protease and
      reverse transcriptase.
AB  - Human immunodeficiency virus (HIV-1) is, like most pathogens, under selective
      pressure to escape the immune system of its host. In particular, HIV-1 can avoid
      recognition by cytotoxic T lymphocytes (CTLs) by altering the binding affinity of
      viral peptides to human leukocyte antigen (HLA) molecules, the role of which is
      to present those peptides to the immune system. It is generally assumed that HLA
      escape mutations carry a replicative fitness cost, but these costs have not been
      quantified. In this study, we assess the replicative cost of mutations which are
      likely to escape presentation by HLA molecules in the region of HIV-1 protease
      and reverse transcriptase. Specifically, we combine computational approaches for
      prediction of in vitro replicative fitness and peptide binding affinity to HLA
      molecules. We find that mutations which impair binding to HLA-A molecules tend to
      have lower in vitro replicative fitness than mutations which do not impair
      binding to HLA-A molecules, suggesting that HLA-A escape mutations carry higher
      fitness costs than non-escape mutations. We argue that the association between
      fitness and HLA-A binding impairment is probably due to an intrinsic cost of
      escape from HLA-A molecules, and these costs are particularly strong for HLA-A
      alleles associated with efficient virus control. Counter-intuitively, we do not
      observe a significant effect in the case of HLA-B, but, as discussed, this does
      not argue against the relevance of HLA-B in virus control. Overall, this article
      points to the intriguing possibility that HLA-A molecules preferentially target
      more conserved regions of HIV-1, emphasizing the importance of HLA-A genes in the
      evolution of HIV-1 and RNA viruses in general.

PMID- 22654657
TI  - A computational investigation on the connection between dynamics properties of
      ribosomal proteins and ribosome assembly.
AB  - Assembly of the ribosome from its protein and RNA constituents has been studied
      extensively over the past 50 years, and experimental evidence suggests that
      prokaryotic ribosomal proteins undergo conformational changes during assembly.
      However, to date, no studies have attempted to elucidate these conformational
      changes. The present work utilizes computational methods to analyze protein
      dynamics and to investigate the linkage between dynamics and binding of these
      proteins during the assembly of the ribosome. Ribosomal proteins are known to be
      positively charged and we find the percentage of positive residues in r-proteins
      to be about twice that of the average protein: Lys+Arg is 18.7% for E. coli and
      21.2% for T. thermophilus. Also, positive residues constitute a large proportion
      of RNA contacting residues: 39% for E. coli and 46% for T. thermophilus. This
      affirms the known importance of charge-charge interactions in the assembly of the
      ribosome. We studied the dynamics of three primary proteins from E. coli and T.
      thermophilus 30S subunits that bind early in the assembly (S15, S17, and S20)
      with atomic molecular dynamic simulations, followed by a study of all r-proteins
      using elastic network models. Molecular dynamics simulations show that solvent
      exposed proteins (S15 and S17) tend to adopt more stable solution conformations
      than an RNA-embedded protein (S20). We also find protein residues that contact
      the 16S rRNA are generally more mobile in comparison with the other residues.
      This is because there is a larger proportion of contacting residues located in
      flexible loop regions. By the use of elastic network models, which are
      computationally more efficient, we show that this trend holds for most of the 30S
      r-proteins.

PMID- 22654658
TI  - cAMP and EPAC are key players in the regulation of the signal transduction
      pathway involved in the alpha-hemolysin autophagic response.
AB  - Staphylococcus aureus is a microorganism that causes serious diseases in the
      human being. This microorganism is able to escape the phagolysosomal pathway,
      increasing intracellular bacterial survival and killing the eukaryotic host cell
      to spread the infection. One of the key features of S. aureus infection is the
      production of a series of virulence factors, including secreted enzymes and
      toxins. We have shown that the pore-forming toxin alpha-hemolysin (Hla) is the S.
      aureus-secreted factor responsible for the activation of the autophagic pathway
      and that this response occurs through a PI3K/Beclin1-independent form. In the
      present report we demonstrate that cAMP has a key role in the regulation of this
      autophagic response. Our results indicate that cAMP is able to inhibit the
      autophagy induced by Hla and that PKA, the classical cAMP effector, does not
      participate in this regulation. We present evidence that EPAC and Rap2b, through
      calpain activation, are the proteins involved in the regulation of Hla-induced
      autophagy. Similar results were obtained in cells infected with different S.
      aureus strains. Interestingly, in this report we show, for the first time to our
      knowledge, that both EPAC and Rap2b are recruited to the S. aureus-containing
      phagosome. We believe that our findings have important implications in
      understanding innate immune processes involved in intracellular pathogen invasion
      of the host cell.

PMID- 22654659
TI  - Comparative genomics reveals two novel RNAi factors in Trypanosoma brucei and
      provides insight into the core machinery.
AB  - The introduction ten years ago of RNA interference (RNAi) as a tool for molecular
      exploration in Trypanosoma brucei has led to a surge in our understanding of the
      pathogenesis and biology of this human parasite. In particular, a genome-wide
      RNAi screen has recently been combined with next-generation Illumina sequencing
      to expose catalogues of genes associated with loss of fitness in distinct
      developmental stages. At present, this technology is restricted to RNAi-positive
      protozoan parasites, which excludes T. cruzi, Leishmania major, and Plasmodium
      falciparum. Therefore, elucidating the mechanism of RNAi and identifying the
      essential components of the pathway is fundamental for improving RNAi efficiency
      in T. brucei and for transferring the RNAi tool to RNAi-deficient pathogens. Here
      we used comparative genomics of RNAi-positive and -negative trypanosomatid
      protozoans to identify the repertoire of factors in T. brucei. In addition to the
      previously characterized Argonaute 1 (AGO1) protein and the cytoplasmic and
      nuclear Dicers, TbDCL1 and TbDCL2, respectively, we identified the RNA
      Interference Factors 4 and 5 (TbRIF4 and TbRIF5). TbRIF4 is a 3'-5' exonuclease
      of the DnaQ superfamily and plays a critical role in the conversion of duplex
      siRNAs to the single-stranded form, thus generating a TbAGO1-siRNA complex
      required for target-specific cleavage. TbRIF5 is essential for cytoplasmic RNAi
      and appears to act as a TbDCL1 cofactor. The availability of the core RNAi
      machinery in T. brucei provides a platform to gain mechanistic insights in this
      ancient eukaryote and to identify the minimal set of components required to
      reconstitute RNAi in RNAi-deficient parasites.

PMID- 22654660
TI  - In vitro and in vivo isolation and characterization of Duvenhage virus.
AB  - A fatal human case of Duvenhage virus (DUVV) infection in a Dutch traveller who
      had returned from Kenya was reported in 2007. She exhibited classical symptoms of
      rabies encephalitis with distinct pathological findings. In the present study we
      describe the isolation and characterization of DUVV in vitro and its passage in
      BALB/c mice. The virus proved to be neuroinvasive in both juvenile and adult
      mice, resulting in about 50% lethality upon peripheral infection. Clinical signs
      in infected mice were those of classical rabies. However, the distribution of
      viral antigen expression in the brain differed from that of classical rabies
      virus infection and neither inclusion bodies nor neuronal necrosis were observed.
      This is the first study to describe the in vitro and in vivo isolation and
      characterization of DUVV.

PMID- 22654661
TI  - The [Het-s] prion, an amyloid fold as a cell death activation trigger.

PMID- 22654662
TI  - Analysis of functional differences between hepatitis C virus NS5A of genotypes 1
      7 in infectious cell culture systems.
AB  - Hepatitis C virus (HCV) is an important cause of chronic liver disease. Several
      highly diverse HCV genotypes exist with potential key functional differences. The
      HCV NS5A protein was associated with response to interferon (IFN)-alpha based
      therapy, and is a primary target of currently developed directly-acting antiviral
      compounds. NS5A is important for replication and virus production, but has not
      been studied for most HCV genotypes. We studied the function of NS5A using
      infectious NS5A genotype 1-7 cell culture systems, and through reverse genetics
      demonstrated a universal importance of the amphipathic alpha-helix, domain I and
      II and the low-complexity sequence (LCS) I for HCV replication; the replicon
      enhancing LCSI mutation S225P attenuated all genotypes. Mutation of conserved
      prolines in LCSII led to minor reductions in virus production for the
      JFH1(genotype 2a) NS5A recombinant, but had greater effects on other isolates;
      replication was highly attenuated for ED43(4a) and QC69(7a) recombinants.
      Deletion of the conserved residues 414-428 in domain III reduced virus production
      for most recombinants but not JFH1(2a). Reduced virus production was linked to
      attenuated replication in all cases, but ED43(4a) and SA13(5a) also displayed
      impaired particle assembly. Compared to the original H77C(1a) NS5A recombinant,
      the changes in LCSII and domain III reduced the amounts of NS5A present. For
      H77C(1a) and TN(1a) NS5A recombinants, we observed a genetic linkage between NS5A
      and p7, since introduced changes in NS5A led to changes in p7 and vice versa.
      Finally, NS5A function depended on genotype-specific residues in domain I, as
      changing genotype 2a-specific residues to genotype 1a sequence and vice versa led
      to highly attenuated mutants. In conclusion, this study identified NS5A genetic
      elements essential for all major HCV genotypes in infectious cell culture
      systems. Genotype- or isolate- specific NS5A functional differences were
      identified, which will be important for understanding of HCV NS5A function and
      therapeutic targeting.

PMID- 22654663
TI  - Chitohexaose activates macrophages by alternate pathway through TLR4 and blocks
      endotoxemia.
AB  - Sepsis is a consequence of systemic bacterial infections leading to hyper
      activation of immune cells by bacterial products resulting in enhanced release of
      mediators of inflammation. Endotoxin (LPS) is a major component of the outer
      membrane of Gram negative bacteria and a critical factor in pathogenesis of
      sepsis. Development of antagonists that inhibit the storm of inflammatory
      molecules by blocking Toll like receptors (TLR) has been the main stay of
      research efforts. We report here that a filarial glycoprotein binds to murine
      macrophages and human monocytes through TLR4 and activates them through alternate
      pathway and in the process inhibits LPS mediated classical activation which leads
      to inflammation associated with endotoxemia. The active component of the nematode
      glycoprotein mediating alternate activation of macrophages was found to be a
      carbohydrate residue, Chitohexaose. Murine macrophages and human monocytes up
      regulated Arginase-1 and released high levels of IL-10 when incubated with
      chitohexaose. Macrophages of C3H/HeJ mice (non-responsive to LPS) failed to get
      activated by chitohexaose suggesting that a functional TLR4 is critical for
      alternate activation of macrophages also. Chitohexaose inhibited LPS induced
      production of inflammatory molecules TNF-alpha, IL-1beta and IL-6 by macropahges
      in vitro and in vivo in mice. Intraperitoneal injection of chitohexaose
      completely protected mice against endotoxemia when challenged with a lethal dose
      of LPS. Furthermore, Chitohexaose was found to reverse LPS induced endotoxemia in
      mice even 6/24/48 hrs after its onset. Monocytes of subjects with active filarial
      infection displayed characteristic alternate activation markers and were
      refractory to LPS mediated inflammatory activation suggesting an interesting
      possibility of subjects with filarial infections being less prone to develop of
      endotoxemia. These observations that innate activation of alternate pathway of
      macrophages by chtx through TLR4 has offered novel opportunities to cell
      biologists to study two mutually exclusive activation pathways of macrophages
      being mediated through a single receptor.

PMID- 22654664
TI  - Cellular levels and binding of c-di-GMP control subcellular localization and
      activity of the Vibrio cholerae transcriptional regulator VpsT.
AB  - The second messenger, cyclic diguanylate (c-di-GMP), regulates diverse cellular
      processes in bacteria. C-di-GMP is produced by diguanylate cyclases (DGCs),
      degraded by phosphodiesterases (PDEs), and receptors couple c-di-GMP production
      to cellular responses. In many bacteria, including Vibrio cholerae, multiple DGCs
      and PDEs contribute to c-di-GMP signaling, and it is currently unclear whether
      the compartmentalization of c-di-GMP signaling components is required to mediate
      c-di-GMP signal transduction. In this study we show that the transcriptional
      regulator, VpsT, requires c-di-GMP binding for subcellular localization and
      activity. Only the additive deletion of five DGCs markedly decreases the
      localization of VpsT, while single deletions of each DGC do not impact VpsT
      localization. Moreover, mutations in residues required for c-di-GMP binding, c-di
      GMP-stabilized dimerization and DNA binding of VpsT abrogate wild type
      localization and activity. VpsT does not co-localize or interact with DGCs
      suggesting that c-di-GMP from these DGCs diffuses to VpsT, supporting a model in
      which c-di-GMP acts at a distance. Furthermore, VpsT localization in a
      heterologous host, Escherichia coli, requires a catalytically active DGC and is
      enhanced by the presence of VpsT-target sequences. Our data show that c-di-GMP
      signaling can be executed through an additive cellular c-di-GMP level from
      multiple DGCs affecting the localization and activity of a c-di-GMP receptor and
      furthers our understanding of the mechanisms of second messenger signaling.

PMID- 22654665
TI  - Polydnavirus Ank proteins bind NF-kappaB homodimers and inhibit processing of
      Relish.
AB  - Recent studies have greatly increased understanding of how the immune system of
      insects responds to infection, whereas much less is known about how pathogens
      subvert immune defenses. Key regulators of the insect immune system are Rel
      proteins that form Nuclear Factor-kappaB (NF-kappaB) transcription factors, and
      inhibitor kappaB (IkappaB) proteins that complex with and regulate NF-kappaBs.
      Major mortality agents of insects are parasitoid wasps that carry
      immunosuppressive polydnaviruses (PDVs). Most PDVs encode ank genes that share
      features with IkappaBs, while our own prior studies suggested that two ank family
      members from Microplitis demolitor bracovirus (MdBV) (Ank-H4 and Ank-N5) behave
      as IkappaB mimics. However, the binding affinities of these viral mimics for Rel
      proteins relative to endogenous IkappaBs remained unclear. Surface plasmon
      resonance (SPR) and co-immunoprecipitation assays showed that the IkappaB Cactus
      from Drosophila bound Dif and Dorsal homodimers more strongly than Relish
      homodimers. Ank-H4 and -N5 bound Dif, Dorsal and Relish homodimers with higher
      affinity than the IkappaB domain of Relish (Rel-49), and also bound Relish
      homodimers more strongly than Cactus. Ank-H4 and -N5 inhibited processing of
      compound Relish and reduced the expression of several antimicrobial peptide genes
      regulated by the Imd signaling pathway in Drosophila mbn2 cells. Studies
      conducted in the natural host Pseudoplusia includens suggested that parasitism by
      M. demolitor also activates NF-kappaB signaling and that MdBV inhibits this
      response. Overall, our data provide the first quantitative measures of insect and
      viral IkappaB binding affinities, while also showing that viral mimics disable
      Relish processing.

PMID- 22654666
TI  - Hsp90 interacts specifically with viral RNA and differentially regulates
      replication initiation of Bamboo mosaic virus and associated satellite RNA.
AB  - Host factors play crucial roles in the replication of plus-strand RNA viruses. In
      this report, a heat shock protein 90 homologue of Nicotiana benthamiana, NbHsp90,
      was identified in association with partially purified replicase complexes from
      BaMV-infected tissue, and shown to specifically interact with the 3' untranslated
      region (3' UTR) of BaMV genomic RNA, but not with the 3' UTR of BaMV-associated
      satellite RNA (satBaMV RNA) or that of genomic RNA of other viruses, such as
      Potato virus X (PVX) or Cucumber mosaic virus (CMV). Mutational analyses revealed
      that the interaction occurs between the middle domain of NbHsp90 and domain E of
      the BaMV 3' UTR. The knockdown or inhibition of NbHsp90 suppressed BaMV
      infectivity, but not that of satBaMV RNA, PVX, or CMV in N. benthamiana. Time
      course analysis further revealed that the inhibitory effect of 17-AAG is
      significant only during the immediate early stages of BaMV replication. Moreover,
      yeast two-hybrid and GST pull-down assays demonstrated the existence of an
      interaction between NbHsp90 and the BaMV RNA-dependent RNA polymerase. These
      results reveal a novel role for NbHsp90 in the selective enhancement of BaMV
      replication, most likely through direct interaction with the 3' UTR of BaMV RNA
      during the initiation of BaMV RNA replication.

PMID- 22654667
TI  - Twist1 suppresses senescence programs and thereby accelerates and maintains
      mutant Kras-induced lung tumorigenesis.
AB  - KRAS mutant lung cancers are generally refractory to chemotherapy as well
      targeted agents. To date, the identification of drugs to therapeutically inhibit
      K-RAS have been unsuccessful, suggesting that other approaches are required. We
      demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in
      human lung tumors that the inhibition of Twist1 restores a senescence program
      inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a
      transcription factor that is essential during embryogenesis. Twist1 has been
      suggested to play an important role during tumor progression. However, there is
      no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis.
      Through two novel transgenic mouse models, we show that Twist1 cooperates with
      Kras(G12D) to markedly accelerate lung tumorigenesis by abrogating cellular
      senescence programs and promoting the progression from benign adenomas to
      adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is
      sufficient to cause Kras mutant lung tumors to undergo senescence and lose their
      neoplastic features. Finally, we analyzed more than 500 human tumors to
      demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors.
      The suppression of TWIST1 in human lung cancer cells also induced cellular
      senescence. Hence, TWIST1 is a critical regulator of cellular senescence
      programs, and the suppression of TWIST1 in human tumors may be an effective
      example of pro-senescence therapy.

PMID- 22654668
TI  - KATNAL1 regulation of sertoli cell microtubule dynamics is essential for
      spermiogenesis and male fertility.
AB  - Spermatogenesis is a complex process reliant upon interactions between germ cells
      (GC) and supporting somatic cells. Testicular Sertoli cells (SC) support GCs
      during maturation through physical attachment, the provision of nutrients, and
      protection from immunological attack. This role is facilitated by an active
      cytoskeleton of parallel microtubule arrays that permit transport of nutrients to
      GCs, as well as translocation of spermatids through the seminiferous epithelium
      during maturation. It is well established that chemical perturbation of SC
      microtubule remodelling leads to premature GC exfoliation demonstrating that
      microtubule remodelling is an essential component of male fertility, yet the
      genes responsible for this process remain unknown. Using a random ENU mutagenesis
      approach, we have identified a novel mouse line displaying male-specific
      infertility, due to a point mutation in the highly conserved ATPase domain of the
      novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A
      like1 (KATNAL1). We demonstrate that Katnal1 is expressed in testicular Sertoli
      cells (SC) from 15.5 days post-coitum (dpc) and that, consistent with chemical
      disruption models, loss of function of KATNAL1 leads to male-specific infertility
      through disruption of SC microtubule dynamics and premature exfoliation of
      spermatids from the seminiferous epithelium. The identification of KATNAL1 as an
      essential regulator of male fertility provides a significant novel entry point
      into advancing our understanding of how SC microtubule dynamics promotes male
      fertility. Such information will have resonance both for future treatment of male
      fertility and the development of non-hormonal male contraceptives.

PMID- 22654669
TI  - An essential role for katanin p80 and microtubule severing in male gamete
      production.
AB  - Katanin is an evolutionarily conserved microtubule-severing complex implicated in
      multiple aspects of microtubule dynamics. Katanin consists of a p60 severing
      enzyme and a p80 regulatory subunit. The p80 subunit is thought to regulate
      complex targeting and severing activity, but its precise role remains elusive. In
      lower-order species, the katanin complex has been shown to modulate mitotic and
      female meiotic spindle dynamics and flagella development. The in vivo function of
      katanin p80 in mammals is unknown. Here we show that katanin p80 is essential for
      male fertility. Specifically, through an analysis of a mouse loss-of-function
      allele (the Taily line), we demonstrate that katanin p80, most likely in
      association with p60, has an essential role in male meiotic spindle assembly and
      dissolution and the removal of midbody microtubules and, thus, cytokinesis.
      Katanin p80 also controls the formation, function, and dissolution of a
      microtubule structure intimately involved in defining sperm head shaping and
      sperm tail formation, the manchette, and plays a role in the formation of axoneme
      microtubules. Perturbed katanin p80 function, as evidenced in the Taily mouse,
      results in male sterility characterized by decreased sperm production, sperm with
      abnormal head shape, and a virtual absence of progressive motility. Collectively
      these data demonstrate that katanin p80 serves an essential and evolutionarily
      conserved role in several aspects of male germ cell development.

PMID- 22654670
TI  - A duplication CNV that conveys traits reciprocal to metabolic syndrome and
      protects against diet-induced obesity in mice and men.
AB  - The functional contribution of CNV to human biology and disease pathophysiology
      has undergone limited exploration. Recent observations in humans indicate a
      tentative link between CNV and weight regulation. Smith-Magenis syndrome (SMS),
      manifesting obesity and hypercholesterolemia, results from a deletion CNV at
      17p11.2, but is sometimes due to haploinsufficiency of a single gene, RAI1. The
      reciprocal duplication in 17p11.2 causes Potocki-Lupski syndrome (PTLS). We
      previously constructed mouse strains with a deletion, Df(11)17, or duplication,
      Dp(11)17, of the mouse genomic interval syntenic to the SMS/PTLS region. We
      demonstrate that Dp(11)17 is obesity-opposing; it conveys a highly penetrant,
      strain-independent phenotype of reduced weight, leaner body composition, lower
      TC/LDL, and increased insulin sensitivity that is not due to alteration in food
      intake or activity level. When fed with a high-fat diet, Dp(11)17/+ mice display
      much less weight gain and metabolic change than WT mice, demonstrating that the
      Dp(11)17 CNV protects against metabolic syndrome. Reciprocally, Df(11)17/+ mice
      with the deletion CNV have increased weight, higher fat content, decreased HDL,
      and reduced insulin sensitivity, manifesting a bona fide metabolic syndrome.
      These observations in the deficiency animal model are supported by human data
      from 76 SMS subjects. Further, studies on knockout/transgenic mice showed that
      the metabolic consequences of Dp(11)17 and Df(11)17 CNVs are not only due to
      dosage alterations of Rai1, the predominant dosage-sensitive gene for SMS and
      likely also PTLS. Our experiments in chromosome-engineered mouse CNV models for
      human genomic disorders demonstrate that a CNV can be causative for
      weight/metabolic phenotypes. Furthermore, we explored the biology underlying the
      contribution of CNV to the physiology of weight control and energy metabolism.
      The high penetrance, strain independence, and resistance to dietary influences
      associated with the CNVs in this study are features distinct from most SNP
      associated metabolic traits and further highlight the potential importance of CNV
      in the etiology of both obesity and MetS as well as in the protection from these
      traits.

PMID- 22654672
TI  - abd-A regulation by the iab-8 noncoding RNA.
AB  - The homeotic genes in Drosophila melanogaster are aligned on the chromosome in
      the order of the body segments that they affect. The genes affecting the more
      posterior segments repress the more anterior genes. This posterior dominance rule
      must be qualified in the case of abdominal-A (abd-A) repression by Abdominal-B
      (Abd-B). Animals lacking Abd-B show ectopic expression of abd-A in the epidermis
      of the eighth abdominal segment, but not in the central nervous system.
      Repression in these neuronal cells is accomplished by a 92 kb noncoding RNA. This
      "iab-8 RNA" produces a micro RNA to repress abd-A, but also has a second,
      redundant repression mechanism that acts only "in cis." Transcriptional
      interference with the abd-A promoter is the most likely mechanism.

PMID- 22654671
TI  - Knowledge-driven analysis identifies a gene-gene interaction affecting high
      density lipoprotein cholesterol levels in multi-ethnic populations.
AB  - Total cholesterol, low-density lipoprotein cholesterol, triglyceride, and high
      density lipoprotein cholesterol (HDL-C) levels are among the most important risk
      factors for coronary artery disease. We tested for gene-gene interactions
      affecting the level of these four lipids based on prior knowledge of established
      genome-wide association study (GWAS) hits, protein-protein interactions, and
      pathway information. Using genotype data from 9,713 European Americans from the
      Atherosclerosis Risk in Communities (ARIC) study, we identified an interaction
      between HMGCR and a locus near LIPC in their effect on HDL-C levels (Bonferroni
      corrected P(c) = 0.002). Using an adaptive locus-based validation procedure, we
      successfully validated this gene-gene interaction in the European American
      cohorts from the Framingham Heart Study (P(c) = 0.002) and the Multi-Ethnic Study
      of Atherosclerosis (MESA; P(c) = 0.006). The interaction between these two loci
      is also significant in the African American sample from ARIC (P(c) = 0.004) and
      in the Hispanic American sample from MESA (P(c) = 0.04). Both HMGCR and LIPC are
      involved in the metabolism of lipids, and genome-wide association studies have
      previously identified LIPC as associated with levels of HDL-C. However, the
      effect on HDL-C of the novel gene-gene interaction reported here is twice as
      pronounced as that predicted by the sum of the marginal effects of the two loci.
      In conclusion, based on a knowledge-driven analysis of epistasis, together with a
      new locus-based validation method, we successfully identified and validated an
      interaction affecting a complex trait in multi-ethnic populations.

PMID- 22654673
TI  - UDP-galactose 4'-epimerase activities toward UDP-Gal and UDP-GalNAc play
      different roles in the development of Drosophila melanogaster.
AB  - In both humans and Drosophila melanogaster, UDP-galactose 4'-epimerase (GALE)
      catalyzes two distinct reactions, interconverting UDP-galactose (UDP-gal) and UDP
      glucose (UDP-glc) in the final step of the Leloir pathway of galactose
      metabolism, and also interconverting UDP-N-acetylgalactosamine (UDP-galNAc) and
      UDP-N-acetylglucosamine (UDP-glcNAc). All four of these UDP-sugars serve as vital
      substrates for glycosylation in metazoans. Partial loss of GALE in humans results
      in the spectrum disorder epimerase deficiency galactosemia; partial loss of GALE
      in Drosophila melanogaster also results in galactose-sensitivity, and complete
      loss in Drosophila is embryonic lethal. However, whether these outcomes in both
      humans and flies result from loss of one GALE activity, the other, or both has
      remained unknown. To address this question, we uncoupled the two activities in a
      Drosophila model, effectively replacing the endogenous dGALE with prokaryotic
      transgenes, one of which (Escherichia coli GALE) efficiently interconverts only
      UDP-gal/UDP-glc, and the other of which (Plesiomonas shigelloides wbgU)
      efficiently interconverts only UDP-galNAc/UDP-glcNAc. Our results demonstrate
      that both UDP-gal and UDP-galNAc activities of dGALE are required for Drosophila
      survival, although distinct roles for each activity can be seen in specific
      windows of developmental time or in response to a galactose challenge. By
      extension, these data also suggest that both activities might play distinct and
      essential roles in humans.

PMID- 22654674
TI  - TBC-8, a putative RAB-2 GAP, regulates dense core vesicle maturation in
      Caenorhabditis elegans.
AB  - Dense core vesicles (DCVs) are thought to be generated at the late Golgi
      apparatus as immature DCVs, which subsequently undergo a maturation process
      through clathrin-mediated membrane remodeling events. This maturation process is
      required for efficient processing of neuropeptides within DCVs and for removal of
      factors that would otherwise interfere with DCV release. Previously, we have
      shown that the GTPase, RAB-2, and its effector, RIC-19, are involved in DCV
      maturation in Caenorhabditis elegans motoneurons. In rab-2 mutants, specific
      cargo is lost from maturing DCVs and missorted into the endosomal/lysosomal
      degradation route. Cargo loss could be prevented by blocking endosomal delivery.
      This suggests that RAB-2 is involved in retention of DCV components during the
      sorting process at the Golgi-endosomal interface. To understand how RAB-2
      activity is regulated at the Golgi, we screened for RAB-2-specific GTPase
      activating proteins (GAPs). We identified a potential RAB-2 GAP, TBC-8, which is
      exclusively expressed in neurons and which, when depleted, shows similar DCV
      maturation defects as rab-2 mutants. We could demonstrate that RAB-2 binds to its
      putative GAP, TBC-8. Interestingly, TBC-8 also binds to the RAB-2 effector, RIC
      19. This interaction appears to be conserved as TBC-8 also interacted with the
      human ortholog of RIC-19, ICA69. Therefore, we propose that a dynamic ON/OFF
      cycling of RAB-2 at the Golgi induced by the GAP/effector complex is required for
      proper DCV maturation.

PMID- 22654675
TI  - EMT inducers catalyze malignant transformation of mammary epithelial cells and
      drive tumorigenesis towards claudin-low tumors in transgenic mice.
AB  - The epithelial-mesenchymal transition (EMT) is an embryonic transdifferentiation
      process consisting of conversion of polarized epithelial cells to motile
      mesenchymal ones. EMT-inducing transcription factors are aberrantly expressed in
      multiple tumor types and are known to favor the metastatic dissemination process.
      Supporting oncogenic activity within primary lesions, the TWIST and ZEB proteins
      can prevent cells from undergoing oncogene-induced senescence and apoptosis by
      abolishing both p53- and RB-dependent pathways. Here we show that they also
      downregulate PP2A phosphatase activity and efficiently cooperate with an
      oncogenic version of H-RAS in malignant transformation of human mammary
      epithelial cells. Thus, by down-regulating crucial tumor suppressor functions,
      EMT inducers make cells particularly prone to malignant conversion. Importantly,
      by analyzing transformed cells generated in vitro and by characterizing novel
      transgenic mouse models, we further demonstrate that cooperation between an EMT
      inducer and an active form of RAS is sufficient to trigger transformation of
      mammary epithelial cells into malignant cells exhibiting all the characteristic
      features of claudin-low tumors, including low expression of tight and adherens
      junction genes, EMT traits, and stem cell-like characteristics. Claudin-low
      tumors are believed to be the most primitive breast malignancies, having arisen
      through transformation of an early epithelial precursor with inherent stemness
      properties and metaplastic features. Challenging this prevailing view, we propose
      that these aggressive tumors arise from cells committed to luminal
      differentiation, through a process driven by EMT inducers and combining malignant
      transformation and transdifferentiation.

PMID- 22654678
TI  - Chromosome pairing: a hidden treasure no more.

PMID- 22654679
TI  - An evidence-based review of the potential benefits of taliglucerase alfa in the
      treatment of patients with Gaucher disease.
AB  - Gaucher disease is an inherited lysosomal storage disorder, characterized by
      deficient activity of glucocerebrosidase leading to storage of glucocerebroside
      in tissue macrophages. Type I disease, the most prevalent form, lacks central
      nervous system involvement but presents primarily with variable degrees of
      hepatosplenomegaly, cytopenia, and bone disease. Intravenous enzyme replacement
      therapy can reverse these manifestations. In addition to the two enzymes
      currently authorized for use, the newest enzyme, taliglucerase alfa, is at the
      late stages of clinical development. Taliglucerase alfa is a unique product, as
      it is the first plant cell-based recombinant enzyme therapy. This review
      considers the existing evidence for therapeutic efficacy of taliglucerase alfa in
      the treatment of the non-neuronopathic manifestations of Gaucher disease.
      Clinical studies encompass one phase I trial in healthy volunteers, one phase III
      trial, and preliminary results from both an extension study and a switch study.
      In the 9-month, randomized, double-blind phase III trial, treatment-naive
      patients with type I Gaucher disease were treated with either 30 or 60 U/kg every
      2 weeks. Dose-dependent improvements were achieved after 6 and 9 months of
      therapy, with reductions in spleen and liver volumes and improvements in
      hemoglobin levels. Platelet counts improved initially only in the higher-dose
      group, but preliminary results from the extension study also show significant
      increases in the lower-dose group. Bone marrow involvement, as assessed by
      magnetic resonance imaging, improved in almost all patients. Taliglucerase alfa
      has shown a good safety profile, with few patients experiencing hypersensitivity
      reactions and developing antibodies. An additional enzyme replacement therapy for
      Gaucher disease would enable the treatment of more patients and would provide
      backup for unexpected production problems. Furthermore, it is expected that this
      new treatment would reduce the costs of therapy. Taliglucerase alfa is a valuable
      new treatment modality for the non-neuronopathic manifestations of Gaucher
      disease.

PMID- 22654676
TI  - Regulating repression: roles for the sir4 N-terminus in linker DNA protection and
      stabilization of epigenetic states.
AB  - Silent information regulator proteins Sir2, Sir3, and Sir4 form a heterotrimeric
      complex that represses transcription at subtelomeric regions and homothallic
      mating type (HM) loci in budding yeast. We have performed a detailed biochemical
      and genetic analysis of the largest Sir protein, Sir4. The N-terminal half of
      Sir4 is dispensable for SIR-mediated repression of HM loci in vivo, except in
      strains that lack Yku70 or have weak silencer elements. For HM silencing in these
      cells, the C-terminal domain (Sir4C, residues 747-1,358) must be complemented
      with an N-terminal domain (Sir4N; residues 1-270), expressed either independently
      or as a fusion with Sir4C. Nonetheless, recombinant Sir4C can form a complex with
      Sir2 and Sir3 in vitro, is catalytically active, and has sedimentation properties
      similar to a full-length Sir4-containing SIR complex. Sir4C-containing SIR
      complexes bind nucleosomal arrays and protect linker DNA from nucleolytic
      digestion, but less effectively than wild-type SIR complexes. Consistently, full
      length Sir4 is required for the complete repression of subtelomeric genes.
      Supporting the notion that the Sir4 N-terminus is a regulatory domain, we find it
      extensively phosphorylated on cyclin-dependent kinase consensus sites, some being
      hyperphosphorylated during mitosis. Mutation of two major phosphoacceptor sites
      (S63 and S84) derepresses natural subtelomeric genes when combined with a
      serendipitous mutation (P2A), which alone can enhance the stability of either the
      repressed or active state. The triple mutation confers resistance to rapamycin
      induced stress and a loss of subtelomeric repression. We conclude that the Sir4 N
      terminus plays two roles in SIR-mediated silencing: it contributes to epigenetic
      repression by stabilizing the SIR-mediated protection of linker DNA; and, as a
      target of phosphorylation, it can destabilize silencing in a regulated manner.

PMID- 22654677
TI  - Meiotic chromosome pairing is promoted by telomere-led chromosome movements
      independent of bouquet formation.
AB  - Chromosome pairing in meiotic prophase is a prerequisite for the high fidelity of
      chromosome segregation that haploidizes the genome prior to gamete formation. In
      the budding yeast Saccharomyces cerevisiae, as in most multicellular eukaryotes,
      homologous pairing at the cytological level reflects the contemporaneous search
      for homology at the molecular level, where DNA double-strand broken ends find and
      interact with templates for repair on homologous chromosomes. Synapsis
      (synaptonemal complex formation) stabilizes pairing and supports DNA repair. The
      bouquet stage, where telomeres have formed a transient single cluster early in
      meiotic prophase, and telomere-promoted rapid meiotic prophase chromosome
      movements (RPMs) are prominent temporal correlates of pairing and synapsis. The
      bouquet has long been thought to contribute to the kinetics of pairing, but the
      individual roles of bouquet and RPMs are difficult to assess because of common
      dependencies. For example, in budding yeast RPMs and bouquet both require the
      broadly conserved SUN protein Mps3 as well as Ndj1 and Csm4, which link telomeres
      to the cytoskeleton through the intact nuclear envelope. We find that mutants in
      these genes provide a graded series of RPM activity: wild-type>mps3-dCC>mps3
      dAR>ndj1Delta>mps3-dNT = csm4Delta. Pairing rates are directly correlated with
      RPM activity even though only wild-type forms a bouquet, suggesting that RPMs
      promote homologous pairing directly while the bouquet plays at most a minor role
      in Saccharomyces cerevisiae. A new collision trap assay demonstrates that RPMs
      generate homologous and heterologous chromosome collisions in or before the
      earliest stages of prophase, suggesting that RPMs contribute to pairing by
      stirring the nuclear contents to aid the recombination-mediated homology search.

PMID- 22654680
TI  - Shape design of an optimal comfortable pillow based on the analytic hierarchy
      process method.
AB  - OBJECTIVE: Few studies have analyzed the shapes of pillows. The purpose of this
      study was to investigate the relationship between the pillow shape design and
      subjective comfort level for asymptomatic subjects. METHODS: Four basic pillow
      designs factors were selected on the basis of literature review and recombined
      into 8 configurations for testing the rank of degrees of comfort. The data were
      analyzed by the analytic hierarchy process method to determine the most
      comfortable pillow. RESULTS: Pillow number 4 was the most comfortable pillow in
      terms of head, neck, shoulder, height, and overall comfort. The design factors of
      pillow number 4 were using a combination of standard, cervical, and shoulder
      pillows. A prototype of this pillow was developed on the basis of the study
      results for designing future pillow shapes. CONCLUSIONS: This study investigated
      the comfort level of particular users and redesign features of a pillow. A
      deconstruction analysis would simplify the process of determining the most
      comfortable pillow design and aid designers in designing pillows for groups.

PMID- 22654681
TI  - Reliability and validity of the AutoCAD software method in lumbar lordosis
      measurement.
AB  - OBJECTIVE: The aim of this study was to determine the reliability and validity of
      the AutoCAD software method in lumbar lordosis measurement. METHODS: Fifty
      healthy volunteers with a mean age of 23 +/- 1.80 years were enrolled. A lumbar
      lateral radiograph was taken on all participants, and the lordosis was measured
      according to the Cobb method. Afterward, the lumbar lordosis degree was measured
      via AutoCAD software and flexible ruler methods. The current study is
      accomplished in 2 parts: intratester and intertester evaluations of reliability
      as well as the validity of the flexible ruler and software methods. RESULTS:
      Based on the intraclass correlation coefficient, AutoCAD's reliability and
      validity in measuring lumbar lordosis were 0.984 and 0.962, respectively.
      CONCLUSIONS: AutoCAD showed to be a reliable and valid method to measure
      lordosis. It is suggested that this method may replace those that are costly and
      involve health risks, such as radiography, in evaluating lumbar lordosis.

PMID- 22654682
TI  - The efficacy of the addition of the Pilates method over a minimal intervention in
      the treatment of chronic nonspecific low back pain: a study protocol of a
      randomized controlled trial.
AB  - OBJECTIVE: There is little high-quality evidence on the efficacy of the Pilates
      based exercises for the treatment of chronic nonspecific low back pain.
      Therefore, the objective of this paper is to present a study protocol to
      investigate the efficacy of adding Pilates-based exercises to a minimum
      intervention in patients with chronic non-specific low back pain. METHODS: This
      randomized controlled trial will recruit 86 patients of both sexes, aged between
      18 and 60 years, with chronic non-specific low back pain. The participants will
      be randomly allocated into 2 treatment groups: the Booklet Group, which will
      receive a booklet with postural orientations, and the Pilates Group, which will
      receive the same booklet in addition to a Pilates-based exercises program. The
      general and specific functional capacities of the patient, kinesiophobia, pain
      intensity, and the global perceived effect will be evaluated by a blinded
      assessor before randomization and at 6 weeks and 6 months after randomization. In
      addition, the expectations of the participants and their confidence in the
      treatment will be evaluated before the randomization and after the first
      treatment session, respectively. CONCLUSIONS: It is hoped that the results of
      this study will provide high-quality evidence on the usefulness of Pilates-based
      exercises in the treatment of chronic non-specific low back pain.

PMID- 22654683
TI  - Cox decompression chiropractic manipulation of a patient with postsurgical lumbar
      fusion: a case report.
AB  - OBJECTIVE: The purpose of this case report is to describe a patient with an L5/S1
      posterior surgical fusion who presented to a chiropractic clinic with subsequent
      low back and leg pain and was treated with Cox decompression manipulation.
      CLINICAL FEATURES: A 55-year-old male postal clerk presented to a private
      chiropractic practice with complaints of pain and spasms in his low back
      radiating down the right buttock and leg. His pain was a 5 of 10, and Oswestry
      Disability Index score was 18%. The patient reported a previous surgical fusion
      at L5/S1 for a grade 2 spondylolytic spondylolisthesis. Radiographs revealed
      surgical hardware extending through the pedicles of L5 and S1, fusing the
      posterior arches. INTERVENTION AND OUTCOME: Treatment consisted of ultrasound,
      electric stimulation, and Cox decompression manipulation (flexion distraction) to
      the low back. After 13 treatments, the patient had a complete resolution of his
      symptoms with a pain score of 0 of 10 and an Oswestry score of 2%. A 2-year
      follow-up revealed continued resolution of the patient's symptoms. CONCLUSIONS:
      Cox chiropractic decompression manipulation may be an option for patients with
      back pain subsequent to spinal fusion. More research is needed to verify these
      results.

PMID- 22654684
TI  - Conservative management of a type III acromioclavicular separation: a case report
      and 10-year follow-up.
AB  - OBJECTIVE: The purpose of this study is to present a 10-year prospective case of
      a right incomplete type III acromioclavicular (AC) separation in a 26-year-old
      patient. CLINICAL FEATURES: A 26-year-old male patient fell directly on his right
      shoulder with the arm in an outstretched and overhead position. Pain and swelling
      were immediate and were associated with a "step deformity." The patient had
      limited right shoulder range of motion (ROM), strength, and function.
      Radiographic findings confirmed a type III AC separation on the right. At 1-year
      follow-up, the patient did not report any deficits in ROM or function, but did
      note a prominent distal clavicle on the right. At 3-, 5-, 7-, and 10-year follow
      up, the patient did not report changes from 1 year. The radiographic findings at
      the 10-year follow-up indicated mild degenerative joint disease in both AC joints
      and mild elevation of the distal clavicle on the right. INTERVENTION AND OUTCOME:
      The patient received chiropractic care to control for pain, swelling, and loss of
      ROM. The patient received acupuncture, joint mobilizations, palliative adhesive
      taping of the AC joint, Active Release Technique, and progressive resisted
      exercises. Radiographic study was done at the time of the injury and at 10 years
      to observe for any osseous changes in the AC joint. CONCLUSION: The patient
      yielded excellent results from conservative chiropractic management that was
      reflected in a prompt return to work 19 days after the injury. Follow-up at 1, 3,
      5, 7, and 10 years exhibited absence of residual deficits in ROM and function.
      The "step deformity" was still present after the injury on the right.

PMID- 22654685
TI  - Effects of tea combined with high-protein meal replacement shakes on
      anthropometric measurements, lipid profiles, cellular biochemistry,
      neurochemistry, and microbial metabolism: a prospective observational study.
AB  - OBJECTIVE: The purpose of this study was to report preliminary data on the
      effects of tea and high-protein meal replacement shakes on weight loss, waist-to
      hip ratios, and lipid profiles in healthy subjects. Secondary analyses of urine
      samples assessed pre-post changes in cellular biochemistry, neurochemistry, and
      microbial metabolism. METHODS: This study used a pre-post intervention design
      without a control group. Thirty healthy subjects (20-60 years of age; 23 women
      and 7 men) participated in a 28-day diet intervention program consisting of a
      cleansing day and 6 restricted diet days per week. On cleansing days, the
      subjects drank 4 oz of tea 4 times per day with a recommendation to drink at
      least 64 oz of filtered water. On the restricted diet days, the subjects drank 2
      high-protein meal replacement shakes, consumed one 400- to 600-cal (1674.3-2511.5
      joules) meal consisting of low-glycemic index foods, and drank at least 64 oz of
      filtered water. RESULTS: Multiple paired t tests detected reductions in weight
      (6.4 lb), waist (1.9 in), and hip (1.1 in) measurements and in total cholesterol
      (13.3 mg/dL) and low-density lipoprotein cholesterol (11.4 mg/dL) (P < .05).
      Multiple paired t tests detected significant increases in energy metabolism from
      carbohydrates and amino acids and concomitant increases in oxidative stress (P <
      .05). CONCLUSION: The data support the concept that a low-glycemic load diet
      intervention incorporating tea and high-protein meal replacement shakes may cause
      weight loss and improve lipid profiles. The significant physiologic changes from
      the urine samples did not reflect meaningful metabolic effects.

PMID- 22654686
TI  - Vertebral artery dissection in a patient practicing self-manipulation of the
      neck.
AB  - OBJECTIVE: The purpose of this case report is to describe a patient who regularly
      practiced self-manipulation of her neck who presented with shoulder and neck pain
      and was undergoing a vertebral artery dissection. CLINICAL FEATURES: A 42-year
      old female patient sought care for left shoulder pain with a secondary complaint
      of left lower neck pain. Twelve days prior, she had had "the worst headache of
      her life," which began in her left lower cervical spine and extended to her left
      temporal region. The pain was sudden and severe, was described as sharp and
      burning, and lasted 3 hours. She reported nausea, vomiting, and blurred vision.
      INTERVENTION AND OUTCOME: Initial history and examination suggested that the
      patient's head and neck pain was not musculoskeletal in origin, but vascular. She
      repeatedly requested that an adjustment be performed, but instead was referred to
      the local emergency department for further evaluation. Magnetic resonance
      angiogram revealed a dissection of the left vertebral artery from C6 to the C2-C3
      interspace and a 3-mm dissecting pseudoaneurysm at the C3 level. She underwent
      stent-assisted percutaneous transluminal angioplasty combined with antiplatelet
      therapy (clopidogrel) and experienced a good outcome. CONCLUSION: This case
      suggests that careful history taking and awareness of the symptoms of VAD are
      necessary in cases of sudden head and neck pain. More research is needed on the
      relationship between vertebral artery dissection and self-manipulation of the
      neck.

PMID- 22654687
TI  - Chiropractic care of a 47-year-old woman with chronic Bell's palsy: a case study.
AB  - OBJECTIVE: The purpose of this case study is to describe the effect of
      chiropractic care on a patient with chronic Bell's palsy. CLINICAL FEATURES: A 47
      year-old woman with medically diagnosed Bell's palsy presented for chiropractic
      care. She had experienced right sinus pressure and congestion, lack of facial
      tone on the right, and intermittent tingling of the right side of her face.
      INTERVENTIONS AND OUTCOMES: The patient received high-velocity, low-amplitude
      chiropractic manipulation (adjustments) to the cervical and thoracic spine,
      interferential muscle stimulation, and hydroculation on the trapezius muscles
      bilaterally. Reduction in symptoms occurred following the initial visit and
      continued over the next 9 weeks of care. After the course of a year of
      chiropractic care, the patient reached 90% improvement. CONCLUSIONS: For this
      patient, chiropractic care reduced Bell's palsy symptoms.

PMID- 22654688
TI  - Acupuncture and a gluten-free diet relieve urticaria and eczema in a case of
      undiagnosed dermatitis herpetiformis and atypical or extraintestinal celiac
      disease: a case report.
AB  - OBJECTIVE: The purpose of this case report is to describe the use of acupuncture
      and a gluten-free diet (GFD) for urticaria and severe eczema in a patient with
      undiagnosed dermatitis herpetiformis and atypical or extraintestinal celiac
      disease. CLINICAL FEATURES: A 48-year-old woman presented with intense urticaria,
      eczema, worsening heartburn, chronic constipation, headaches, and an intense
      feeling of heat for 4 months. Results of punch biopsies of the skin lesions and
      laboratory tests were inconclusive. After the acupuncture sessions reported here
      ended, human leukocyte antigen blood typing revealed celiac disease and
      dermatitis herpetiformis-associated human leukocyte antigen DQ-8. Results of an
      endoscopy and colonoscopy were negative. INTERVENTION AND OUTCOME: The patient
      received 3 acupuncture treatments a week for 12 weeks. The patient's symptoms
      began in March 2008. She began using topical and oral steroids and felt that her
      symptoms were not responding. Acupuncture began in July 2008. At the end of the
      first 12 treatments, during which she was using topical and oral steroids, the
      urticaria and constipation resolved completely; and she had temporary relief from
      the heartburn. It is thought that the urticaria and constipation resolved because
      of the acupuncture as that was the only change. At the end of the second 12
      treatments, during which time she had started Optifast, a GFD, the heartburn,
      headache, and eczema resolved. At the end of the third 12 treatments, all her
      symptoms remained resolved. Steroid treatment was discontinued after the first 12
      treatments. CONCLUSION: Acupuncture and diet changes appeared to provide relief
      from the urticaria and eczema of dermatitis herpetiformis beyond that obtained by
      traditional treatment of a GFD alone.

PMID- 22654689
TI  - Chiropractic management of a 30-year-old patient with Parsonage-Turner syndrome.
AB  - OBJECTIVES: The purpose of this case report is to describe the chiropractic
      management of a patient presenting with right arm paralysis and a diagnosis of
      Parsonage-Turner syndrome. CLINICAL FEATURES: After receiving nerve entrapment
      release surgery, a 30-year-old man presented with a right arm contracture,
      atrophy, and weakness with general paralysis of the forearm and index finger of 6
      weeks' duration. INTERVENTION AND OUTCOME: The patient was provided chiropractic
      care that included high-velocity/low-amplitude spinal manipulation based upon
      applied kinesiology manual muscle testing, soft tissue trigger point therapy,
      exercises, and stretches. The patient demonstrated improvement in range of motion
      after the first treatment session. By the eighth treatment, he was able to fully
      straighten his arm. Three years later, the patient reported that he was able to
      do mountain climbing and that his arm was fully functional and pain-free.
      CONCLUSION: For this patient, chiropractic care seemed to be successful in
      relieving his right arm paralysis and restoring normal arm movement.

PMID- 22654690
TI  - Herpes zoster in a 6-month-old infant with 13-year follow-up: a retrospective
      case report.
AB  - OBJECTIVE: The purpose of this report is to present a case of herpes zoster in a
      6-month-old infant, conservatively managed without oral antivirals, and its 13
      year follow-up, demonstrating no sequelae or recurrences. CLINICAL FEATURES: A 6
      month-old white female infant presented with a vesicular rash of the right lower
      extremity to a chiropractic office. The rash consisted of grouped vesicles on
      erythematous plaques, the characteristic herpetiform lesion, distributed in the
      S1 dermatome of the right lower extremity only. The infant's history was
      significant for exposure to chicken pox at age 1 week through siblings.
      Consequently, only one vesicle developed, representing subclinical chicken pox.
      The clinical diagnosis of herpes zoster was made. INTERVENTION AND OUTCOME: The
      infant was treated conservatively at home. Treatment consisted of aluminum
      acetate (Burow) solution compresses 3 times each day, followed by a loose
      dressing. The lesions crusted in 1 week and completely resolved in 2 weeks.
      Follow-up, consisting of 13 years of observation, demonstrated no evidence of
      sequelae, such as postherpetic neuralgia, or recurrence. CONCLUSION: Herpes
      zoster is uncommon in infants; however, it may occur. The presentation of the
      rash is characteristic; but otherwise, the condition differs from that in adults
      in that it is mild and not associated with postherpetic neuralgia. In
      uncomplicated cases, conservative treatment measures support the quick resolution
      with no sequelae.

PMID- 22654692
TI  - Chiropractic management using Cox cervical flexion-distraction technique for a
      disk herniation with left foraminal narrowing in a 64-year-old man.
AB  - OBJECTIVE: The purpose of this case report is to describe chiropractic management
      of a patient with a C6/C7 left posteromedial disk herniation with foraminal
      narrowing and concomitant neurological compromise in the form of left upper
      extremity radiating pain and hypoesthesia/anesthesia using Cox flexion
      distraction technique. CLINICAL FEATURES: A 64-year-old man presented to a
      chiropractic clinic with complaints of neck/left shoulder pain and
      hypoesthesia/anesthesia into the palmar side of his left hand. Magnetic resonance
      images of the cervical spine revealed a left posteromedial C6/C7 disk herniation
      along with foraminal narrowing. In addition, there were other levels of
      degeneration, most noted at the C3/C4 spinal level, which also had significant
      left-sided foraminal narrowing. INTERVENTION AND OUTCOME: Treatment included Cox
      flexion-distraction protocols aimed to reduce nerve root compression along with
      supportive physiological therapeutic interventions to aid with pain reduction and
      functional improvement. The patient was treated a total of 10 times over a course
      of 4 weeks. The patient reported being pain-free and fully functional 8 months
      following the conclusion of care. CONCLUSION: This case study demonstrated the
      use of Cox flexion-distraction for treatment of a patient with a cervical disk
      herniation, foraminal narrowing, and associated radiating pain and radiculopathy
      in the left upper extremity.

PMID- 22654691
TI  - A possible correlation between vitamin D deficiency and loss of smell: 2 case
      reports.
AB  - OBJECTIVE: The purpose of this report is to present 2 cases of diminished
      olfaction that improved with increasing serum levels of vitamin D3. CLINICAL
      FEATURES: Both patients were under the care of medical and chiropractic
      physicians for various complaints. A 47-year-old hyposmic woman was diagnosed
      with vitamin D deficiency who incidentally noticed a progressive return of her
      sense of smell while taking vitamin D supplements as prescribed by her medical
      doctor. A 34-year-old anosmic woman noticed a direct relationship with her
      ability to smell and vitamin D3 supplementation. INTERVENTION AND OUTCOME:
      Treatment for the first patient consisted of vitamin D supplementation of 10 000
      IU a day. Her serum D3 levels increased substantially over a period of 8 months,
      at which time she reported a marked improvement in her sense of smell. The second
      patient was prescribed 50 000 IU of vitamin D a week; and she reported an
      increased ability to smell, although only the strongest of odors. CONCLUSION: A
      link between hypovitaminosis D and a diminished sense of smell was noted in these
      2 individuals.

PMID- 22654693
TI  - Changes in chronic low back pain and cardiovascular risk factors using a
      homeopathic human chorionic gonadotropin-based weight loss program: a case
      report.
AB  - OBJECTIVE: The purpose of this case report is to describe the changes in body
      weight and biochemical markers in a patient who completed a homeopathic human
      chorionic gonadotropin protocol. CASE REPORT: A 52-year-old man reported to an
      integrative medical center (including chiropractic and osteopathic physicians)
      for chronic low back pain. The patient reported a 20-year history of chronic,
      episodic low back pain. A course of spinal manipulative therapy was delivered;
      however, because of the lack of resolution of symptoms, a radiographic
      examination was performed, the result of which was essentially normal. Laboratory
      studies demonstrated hypercholesterolemia, hyperlipidemia, uricemia, and elevated
      blood glucose. A dietary change in treatment approach was selected. INTERVENTION
      AND OUTCOME: The patient was instructed to take 10 drops of a homeopathic human
      chorionic gonadotropin product under the tongue 5 times daily. His total daily
      energy (calorie) was limited for the first 30 days of the program while on the
      homeopathic product. After 4 months, the patient lost a total of 71 lb, pain and
      disability scores improved, and reductions in serum cardiovascular markers were
      noted. CONCLUSION: The findings of this study showed that weight loss seemed to
      affect the patient's chronic low back pain and cardiovascular risk factors.

PMID- 22654694
TI  - A calcific pelvic mass in a woman with chronic spinal pain: a case of mature
      cystic teratoma.
AB  - OBJECTIVE: The purpose of this case is to describe findings of a mature cystic
      teratoma and to further provide differential diagnoses for ovarian pelvic masses
      and calcifications. CLINICAL FEATURES: A 27-year-old woman presented to a
      chiropractic teaching clinic with a chief complaint of chronic multilevel spinal
      pain. During a full spine radiographic examination, radiopaque densities were
      incidentally identified in the pelvic bowl visualized through a gonad shield.
      Follow-up pelvic radiography revealed several radiopacities of uniform density
      localized in the pelvic bowl.  INTERVENTION/OUTCOMES: Medical (gynecological)
      consultation led to ultrasonography of the pelvis that revealed a mature cystic
      teratoma. The patient underwent complete excision of the mass through a
      laparotomy procedure. The patient continued to receive chiropractic treatment of
      her original cervical and lumbar spine complaints, further suggesting that the
      pelvic mass was not a source of her musculoskeletal complaints. CONCLUSION: This
      case demonstrates the detection and proper referral of a patient with a calcific
      mass. The presence of a pelvic mass, suspected of arising from the ovary,
      requires additional diagnostic imaging and careful clinical correlation.

PMID- 22654695
TI  - Preferred sleep position on the side is associated with carpal tunnel syndrome.
AB  - BACKGROUND: Although carpal tunnel syndrome is the most common compressive
      neuropathy, there is no comprehensive theory of its etiology. Because of the
      prevalence of night symptoms, we are interested in the role of sleep position in
      the causation of carpal tunnel syndrome. METHODS: We performed a case-control
      study comparing the prevalence of preferred sleep position in 68 cases and 138
      controls. Analysis was stratified by age and gender and controlled for body mass
      index. RESULTS: We found a strong and significant association between a
      preference for sleeping on the side and the presence of carpal tunnel syndrome in
      men and in women less than 60 years of age. Body mass index was associated with
      carpal tunnel syndrome in women but not men. CONCLUSIONS: Our findings of a
      strong association between the presence of carpal tunnel syndrome and preferred
      sleeping on the side suggest a comprehensive unifying theory of causation.

PMID- 22654696
TI  - Safe limited-open carpal tunnel release in the presence of aberrant anatomy.
AB  - PURPOSE: The presence of aberrant anatomy during a limited-open carpal tunnel
      release does not require conversion to an open procedure. We describe the
      occurrence of aberrant anatomy seen during limited-open carpal tunnel release,
      and suggest the safest way to proceed with carpal tunnel release once aberrant
      anatomy is encountered. METHODS: A retrospective chart review was completed for
      patients who underwent limited-open carpal tunnel release between January 2000
      and June 2007. The surgical record was examined to determine if any aberrant
      anatomy was encountered during the procedure. RESULTS: Of the 1,227 hands
      operated on, 69 anomalies were identified. Two carpal tunnel releases were
      converted to open releases after it was determined that the aberrant motor
      branches precluded safe release with a limited-open technique CONCLUSIONS: An
      understanding of anatomical variations combined with vigilance and careful
      dissection enhances the chance for safe and effective limited-open carpal tunnel
      release.

PMID- 22654697
TI  - The use of anabolic steroids as a strategy in reversing denervation atrophy after
      delayed nerve repair.
AB  - BACKGROUND: Denervation atrophy is one factor contributing to suboptimal motor
      recovery following major nerve repair. The hypertrophic effects of anabolic
      steroids may have a potential role in improving reinnervated muscle strength
      after delayed repair. METHODS: Forty-five immature female Sprague-Dawley rats
      underwent three surgeries and final testing. The tibial nerve was transected in
      the hind limb of the experimental (n = 13) and control (n = 14) animals and
      exposed, but not transected in the sham (n = 15) group animals. Three months
      later, once denervation atrophy was established, all transected nerves underwent
      repair using an autograft from the contralateral limb. After waiting an
      additional month to allow axonal regeneration to the gastrocnemius muscles, the
      rodents were implanted with a subcutaneous infusion pump. For the experimental
      group, nandrolone was administered over the next 30 days via this pump, while the
      control and sham group pumps were filled with carrier only. RESULTS: Final
      testing, 6 weeks later, showed improved muscle contraction strength in the
      steroid-treated animals (72% of sham group strength) compared to control animals
      (57% of sham group strength, p < 0.5). A trend towards increased weight and
      muscle belly diameter in the steroid-treated group was not statistically
      significant. CONCLUSIONS: These findings support the potential role of anabolic
      steroids in improving recovery of atrophic muscle after delayed reinnervation.

PMID- 22654698
TI  - Calcium-dependent signaling in Dupuytren's disease.
AB  - BACKGROUND: Previous studies suggest that Dupuytren's disease is caused by
      fibroblast and myofibroblast contractility. Cell contractility in smooth muscle
      cells is caused by calcium-dependent and calcium-independent signaling
      mechanisms. In the calcium-dependent pathway, calcium/calmodulin activates myosin
      light chain kinase (MLCK). In this study, the effects of calcium/calmodulin
      inhibition with the FDA-approved drug fluphenazine on Dupuytren's fibroblast
      contractility and MLCK expression were tested. METHODS: Fibroblast lines from the
      palmar fascia of patients with Dupuytren's disease were explanted and used for in
      vitro study. The effect of fluphenazine on Dupuytren's fibroblast migration was
      determined using a scratch migration assay, and contractility was determined
      using fibroblast-populated collagen lattice (FPCL) assays. Immunohistochemical
      staining of MLCK in different samples of Dupuytren's tissue and normal fascia
      were compared. RESULTS: Fluphenazine demonstrated a dose-dependent inhibition of
      Dupuytren's fibroblast migration, with the maximum inhibition of migration
      observed at 20 MUM (69.8 +/- 1.9%). Fluphenazine also inhibited FPCL contraction
      in a dose-dependent manner. Maximal inhibition was observed at a fluphenazine
      concentration of 20 MUM (52.5 +/- 6.1%). Immunohistological staining illustrated
      that MLCK was predominantly expressed throughout the cytoplasm of select
      fibroblasts within Dupuytren's nodules, yet was absent in the fibroblasts of
      Dupuytren's cords and normal palmar fascia. CONCLUSIONS: Fluphenazine inhibits
      Dupuytren's fibroblast contractility and migration through inhibition of MLCK in
      vitro. However, the inconsistent expression of MLCK throughout Dupuytren's tissue
      suggests that calcium-dependent signaling may not be a primary mode of
      contracture formation. Fluphenazine inhibition of MLCK is not likely to be a
      target for the treatment of Dupuytren's disease.

PMID- 22654699
TI  - Tourniquet use in upper limb surgery.
AB  - Tourniquets are compressive devices that occlude venous and arterial blood flow
      to limbs and are commonly used in upper limb surgery. With the potential risk of
      complications, there is some debate as to whether tourniquets should continue to
      be routinely used. In this review, we first look at the different designs,
      principles, and practical considerations associated with the use of tourniquets
      in the upper limb. The modern pneumatic tourniquet has many design features that
      enhance its safety profile. Current literature suggests that the risk of
      tourniquet-related complications can be significantly reduced by selecting cuff
      inflation pressures based on the limb occlusion pressure, and by a better
      understanding of the actual level of pressure within the soft tissue, and the
      effects of cuff width and contour. The evidence behind tourniquet time,
      placement, and limb exsanguination is also discussed as well as special
      considerations in patients with diabetes mellitus, hypertension, vascular
      calcification, sickle cell disease and obesity. We also provide an evidence-based
      review of the variety of local and systemic complications that may arise from the
      use of upper limb tourniquets including pain, leakage, and nerve, muscle, and
      skin injuries. The evidence in the literature suggests that upper limb
      tourniquets are beneficial in promoting optimum surgical conditions and modern
      tourniquet use is associated with a low rate of adverse events. With the
      improvement in knowledge and technology, the incidence of adverse events should
      continue to decrease. We recommend the use of tourniquets in upper limb surgery
      where no contraindications exist.

PMID- 22654700
TI  - Epicondylectomy versus denervation for lateral humeral epicondylitis.
AB  - BACKGROUND: Traditional management of lateral humeral epicondylitis ("tennis
      elbow") relies upon antiinflammatory medication, rehabilitation, steroid
      injection, counterforce splinting, and, finally, surgery to the common extensor
      origin. The diversity of surgical approaches for lateral humeral epicondylitis
      (LHE) suggests perhaps that the ideal technique has not been determined.
      Denervation of the lateral humeral epicondyle is the concept of interrupting the
      neural pathway that transmits the pain message. Epicondylectomy may accomplish
      its relief of LHE by denervating the epicondyle. METHODS: Since it is known that
      the posterior branch of the posterior cutaneous nerve of the forearm innervates
      the lateral humeral epicondyle, 30 patients who were treated surgically for
      refractory LHE were retrospectively evaluated. Group 1 consisted of 17 patients
      who were treated with epicondylectomy alone, group II consisted of seven patients
      who were treated with lateral epicondylectomy plus neurectomy, and group III
      consisted of seven patients treated with lateral denervation alone. RESULTS:
      Denervation alone gave statistically significantly greater improvement in pain
      relief (p < 0.001) and statistically significantly faster return to work than did
      epicondylectomy alone (p < 0.001). Denervation plus epicondylectomy gave results
      that were the same as denervation alone. CONCLUSION: It is concluded that
      denervation gives significant relief from LHE once traditional non-surgical
      treatment has failed.

PMID- 22654701
TI  - The total scaphoid titanium arthroplasty: A 15-year experience.
AB  - Scaphoid nonunion followed by necrosis of bone segments is a common pathologic
      condition for the hand surgeon, and the difficulty of its management is well
      known. The total titanium scaphoid replacement, although not well-described in
      the literature, in our experience represents a reasonable choice in the treatment
      of this condition. Strict patient selection is necessary to achieve good clinical
      results. The titanium avoids the silicone synovitis, a well-described
      complication of silastic implants. Furthermore, this technique permits other
      surgical steps in case of failure.

PMID- 22654702
TI  - Early complications of volar plating of distal radius fractures and their
      relationship to surgeon experience.
AB  - BACKGROUND: Fractures of the distal radius are among the most common fractures in
      adults. Recently, there has been a trend towards open reduction and internal
      fixation of these fractures through a volar approach. The purpose of this study
      was to assess the early complications of volar locking plate fixation of distal
      radius fractures with an emphasis on defining the relationship between surgeon
      experience and incidence of complications. MATERIALS AND METHODS: Following IRB
      approval, we conducted a retrospective chart review of the initial 96 distal
      radius fractures (92 patients) treated by open reduction and internal fixation of
      distal radius fracture using a volar locked plate. Our outcome measurements were
      incidence of postoperative complications and radiographic loss of reduction.
      RESULTS: Twenty-two complications occurred in 21 patients. Of these, five
      complications (5%) required surgical treatment or hospitalization. Seventeen
      complications (18%) required no surgical intervention or hospitalization.
      Transient nerve dysfunction was the most common complication, accounting for 12
      of 22 complications. The first 30 patients experienced significantly more
      complications than those treated later in the series (p = 0.03). There was a
      trend towards increased incidence of complications in cases where more than 10
      days elapsed between injury and surgery or where supplementary Kirschner wire
      fixation was used. There was no correlation between patient age, sex, severity of
      fracture, or presence of ulnar styloid fracture and the development of
      complications or loss of reduction. DISCUSSION: The incidence of complications
      decreased significantly with increased surgeon experience, suggesting that many
      of these early complications are avoidable.

PMID- 22654703
TI  - Dorsal tangential view of the wrist to detect screw penetration to the dorsal
      cortex of the distal radius after volar fixed-angle plating.
AB  - BACKGROUND: Extensor tendon irritation and attritional tendon ruptures are well
      recognized complications, secondary to dorsal screw penetration following volar
      plating of the distal radius. Lateral and oblique views of the wrist have limited
      ability to detect such penetration, particularly at the ulnar side of the
      Lister's tubercle. In this report, we conducted an intraoperative fluoroscopic
      study to determine dorsal screw penetration in various positions of the
      wrist/forearm and compared the standard radiographic views (lateral, supination,
      and pronation views) with dorsal tangential view of the wrist. MATERIALS AND
      METHOD: Standard lateral, oblique (in pronation and supination), and dorsal
      tangential views were obtained in 27 consecutive patients undergoing fixation a
      distal radius fractures using a volar plate. The number of penetrating screws in
      each dorsal compartment (second, third, fourth) was recorded in each view. Dorsal
      tangential view was obtained using a mini C-arm intraoperatively and sending the
      beam parallel to the dorsal aspect of the wrist in transverse plane. RESULTS: Of
      the 125 distal screws, 8 screws were seen to be penetrating the dorsal cortex in
      lateral and oblique views, whereas 11 screws were detected in dorsal tangential
      view. CONCLUSION: The screw penetration to the third dorsal compartment was
      missed in standard views, but visualized in dorsal tangential view. We recommend
      the use of dorsal tangential view in addition to standard lateral and oblique
      views during volar plating of the distal radius.

PMID- 22654705
TI  - Investigation of radialization and rerouting of the extensor digiti minimi (EDM)
      in the abduction deformity of the little finger: a cadaver study.
AB  - BACKGROUND: One of several operations to correct abduction deformity of the
      little finger, (Wartenberg's sign) in ulnar nerve palsy, is a combined procedure
      that radializes the extensor digiti minimi (EDM) at the level of the fifth
      metacarpophalangeal (MCP) joint and reroutes it from the fifth to fourth extensor
      compartment. This cadaveric study was designed to investigate the impact of both
      elements on adduction. MATERIALS AND METHODS: Anatomy of the little finger
      extensor apparatus was studied in 16 freshly frozen cadaver hands sectioned at
      mid forearm. We observed little finger motion after different modifications of
      the EDM. We tested the effect of a rerouting maneuver by pulling on the EDM, as
      well as radialization of the EDM alone and in combination with rerouting.
      RESULTS: The EDM was present in all cases. Little finger extensor digitorum
      communis (EDC(V)) was missing in two cadavers. In no case was adduction created
      by rerouting the EDM to the fourth compartment. Radialization of the EDM
      corrected the abduction deformity beyond the axis of abduction/adduction of the
      fifth MCP joint in 13 cases and only up to it in three cases. In one of the three
      with limited correction, a rerouting maneuver allowed for further adduction.
      CONCLUSION: The key to correct abduction deformity of the little finger is
      radialization of the EDM, which can be done through a solitary incision at the
      level of the MCP joint. Rerouting alone does not correct the abduction deformity,
      and in combination with radialization it does not predictably enhance the
      correction.

PMID- 22654704
TI  - Refining the sensory and motor ratunculus of the rodent upper extremity:
      evaluation of the C7 nerve root using fMRI and direct nerve stimulation.
AB  - BACKGROUND: Since the 1980s, the C7 nerve root has gained clinical relevance as a
      donor nerve in severe brachial plexus root avulsion injuries. Despite success
      with the cross-chest C7 nerve transfer, inducing injury on an otherwise normal
      side hinders global acceptance. By sacrificing the C7 nerve root, a predictable
      pattern of transient sequelae is seen, including extensor weakness and index and
      middle finger anesthesia. The purpose of this study is to observe cortical
      activity during direct stimulation of the C7 nerve root using blood oxygen level
      dependent functional magnetic resonance imaging (fMRI) in a rat model. METHODS: A
      total of 12 male Sprague-Dawley rats, weighing 200-250 g, were used in this
      study. Following an acclimation period of 1 week, 12 rats underwent exposure and
      dissection of the brachial plexus. Seven rats underwent placement of an
      implantable electrode (AISI 304, Plastics1, Roanoke, VA, USA) on the C7 nerve
      root, while five rats underwent electrode placement on the radial nerve. All
      animals then underwent fMRI during direct nerve stimulation. Ten consecutive
      coronal images were obtained during nerve stimulation, using a 9.4-T small-animal
      MRI scanner. RESULTS: Cortical activation is seen within a very specific area of
      the primary sensory region of the forelimb during C7 nerve root stimulation. The
      cortical activation seen during radial nerve stimulation includes that seen
      during C7 stimulation but extends several slices caudally. CONCLUSIONS: The
      sensory representation of the C7 nerve root is seen in only a small area in the
      S1FL region compared to that seen in the terminal branches of the brachial
      plexus. However, this area shows a significant overlap with the S1FL area of
      activation seen during radial nerve stimulation. This makes sense as the C7 nerve
      root contributes some, but not all, sensory axons to the radial nerve. Mapping of
      the C7 cortical representation in the rat brain not only adds to the ongoing
      development of the motor and sensory ratunculus but also provides an important
      foundation to study subsequent C7 donor nerve models.

PMID- 22654706
TI  - Acute carpal tunnel syndrome secondary to iatrogenic hemorrhage. A case report.
AB  - Carpal tunnel syndrome is a common compression neuropathy of the median nerve.
      Acute carpal tunnel syndrome (aCTS) is rare, associated with a variety of
      conditions. In this case report we present a patient who developed aCTS and volar
      forearm compartment syndrome after a radial artery line placement, while
      receiving intravenous heparin. The patient underwent immediate forearm fasciotomy
      and surgical release for restoration of nerve function, which resulted in
      improved hand function and mild residual median nerve neuropathy. There is
      controversy whether to discontinue or not anticoagulation in a patient with aCTS.
      In our patient, heparin therapy was restarted on the second postoperative day.

PMID- 22654707
TI  - Hereditary multiple exostoses in the hands and fingers: early presentation and
      early surgical treatment in family members. Case reports.
AB  - Hereditary multiple exostosis (HME) is a benign condition with multiple bony
      tumors with cartilage caps (osteochondromas), mainly presenting in the long and
      flat bones. Usually the presentation for HME is between 2 and 10 years of age and
      most are seen by 4 years of age (Khan et al. 2009). In this paper, we report a
      family with three members (father, son, and a daughter) who had very early
      presentations of HME in the fingers within the first 2 years of age. The son
      presented with bony nodules at 7 months of age, and he required surgery at 13
      months of age for a severe functional deformity of his left ring finger. He also
      had an unusual histological presentation on his osteochondroma that consists of
      only subperiosteal cartilage without ossification.

PMID- 22654708
TI  - Hand involvement in Navajo neurohepatopathy: a case report.
AB  - We report a case of Navajo neurohepatopathy with severe involvement of the hands.
      It is a progressive sensorimotor neuropathy with distal weakness, areflexia, and
      reduced sensation in the extremities associated with acral mutilation. The role
      of possible surgical intervention is demonstrated in this case.

PMID- 22654709
TI  - Palmar fasciitis and polyarthritis syndrome in patients with ovarian cancer-a
      case report and review of the literature.

PMID- 22654710
TI  - Monostotic fibrous dysplasia of the distal radius metaphysis: case report.
AB  - We report the case of a 56-year-old male with distal radius monostotic fibrous
      dysplasia that was detected when the patient suffered a pathologic fracture. This
      case is unusual because of the location of the tumor and the age of the patient.

PMID- 22654712
TI  - An update on neurotrophins.

PMID- 22654711
TI  - A rare injury of ipsilateral mid-third clavicle fracture with acromioclavicular
      joint dislocation.

PMID- 22654713
TI  - Role of neurotrophins in neuropathic pain.
AB  - Neurotrophins (NTs) belong to a family of structurally and functionally related
      proteins, they are the subsets of neurotrophic factors. Neurotrophins are
      responsible for diverse actions in the developing peripheral and central nervous
      systems. They are important regulators of neuronal function, affecting neuronal
      survival and growth. They are able to regulate cell death and survival in
      development as well as in pathophysiologic states. NTs and their receptors are
      expressed in areas of the brain that undergo plasticity, indicating that they are
      able to modulate synaptic plasticity.Recently, neurotrophins have been shown to
      play significant roles in the development and transmission of neuropathic pain.
      Neuropathic pain is initiated by a primary lesion or dysfunction in the nervous
      system. It has a huge impact on the quality of life. It is debilitating and often
      has an associated degree of depression that contributes to decreasing human well
      being. Neuropathic pain ranks at the first place for sanitary costs.Neuropathic
      pain treatment is extremely difficult. Several molecular pathways are involved,
      making it a very complex disease. Excitatory or inhibitory pathways controlling
      neuropathic pain development show altered gene expression, caused by peripheral
      nerve injury. At present there are no valid treatments over time and neuropathic
      pain can be classified as an incurable disease.Nowadays, pain research is
      directing towards new molecular methods. By targeting neurotrophin molecules it
      may be possible to provide better pain control than currently available.

PMID- 22654715
TI  - Neurotrophins in the lower urinary tract: becoming of age.
AB  - The lower urinary tract (LUT) comprises a storage unit, the urinary bladder, and
      an outlet, the urethra. The coordination between the two structures is tightly
      controlled by the nervous system and, therefore, LUT function is highly
      susceptible to injuries to the neuronal pathways involved in micturition control.
      These injuries may include lesions to the spinal cord or to nerve fibres and
      result in micturition dysfunction. A common trait of micturition pathologies,
      irrespective of its origin, is an upregulation in synthesis and secretion of
      neurotrophins, most notably Nerve Growth Factor (NGF) and Brain Derived
      Neurotrophic Factor (BDNF). These neurotrophins are produced by neuronal and non
      neuronal cells and exert their effects upon binding to their high-affinity
      receptors abundantly expressed in the neuronal circuits regulating LUT function.
      In addition, NGF and BDNF are present in detectable amounts in the urine of
      patients suffering from various LUT pathologies, suggesting that analysis of
      urinary NGF and BDNF may serve as likely biomarkers to be studied in tandem with
      other factors when diagnosing patients. Studies with experimental models of
      bladder dysfunction using antagonists of NGF and BDNF receptors as well as
      scavenging agents suggest that those NTs may be key elements in the
      pathophysiology of bladder dysfunctions. In addition, available data indicates
      that NGF and BDNF might constitute future targets for designing new drugs for
      better treatment of bladder dysfunction.

PMID- 22654718
TI  - The complex and multifactorial nature of Alzheimer's disease.

PMID- 22654714
TI  - Neurotrophins role in depression neurobiology: a review of basic and clinical
      evidence.
AB  - Depression is a neuropsychiatric disorder affecting a huge percentage of the
      active population especially in developed countries. Research has devoted much of
      its attention to this problematic and many drugs have been developed and are
      currently prescribed to treat this pathology. Yet, many patients are refractory
      to the available therapeutic drugs, which mainly act by increasing the levels of
      the monoamines serotonin and noradrenaline in the synaptic cleft. Even in the
      cases antidepressants are effective, it is usually observed a delay of a few
      weeks between the onset of treatment and remission of the clinical symptoms.
      Additionally, many of these patients who show remission with antidepressant
      therapy present a relapse of depression upon treatment cessation. Thus research
      has focused on other possible molecular targets, besides monoamines, underlying
      depression. Both basic and clinical evidence indicates that depression is
      associated with several structural and neurochemical changes where the levels of
      neurotrophins, particularly of brain-derived neurotrophic factor (BDNF), are
      altered. Antidepressants, as well as other therapeutic strategies, seem to
      restore these levels. Neuronal atrophy, mostly detected in limbic structures that
      regulate mood and cognition, like the hippocampus, is observed in depressed
      patients and in animal behavioural paradigms for depression. Moreover, chronic
      antidepressant treatment enhances adult hippocampal neurogenesis, supporting the
      notion that this event underlies antidepressants effects. Here we review some of
      the preclinical and clinical studies, aimed at disclosing the role of
      neurotrophins in the pathophysiological mechanisms of depression and the mode of
      action of antidepressants, which favour the neurotrophic/neurogenic hypothesis.

PMID- 22654716
TI  - The neurotrophins and their role in Alzheimer's disease.
AB  - Besides being essential for correct development of the vertebrate nervous system
      the neurotrophins also play a vital role in adult neuron survival, maintenance
      and regeneration. In addition they are implicated in the pathogenesis of certain
      neurodegenerative diseases, and may even provide a therapeutic solution for some.
      In particular there have been a number of studies on the involvement of nerve
      growth factor (NGF) and brain derived neurotrophic factor (BDNF) in the
      development of Alzheimer's disease. This disease is of growing concern as
      longevity increases worldwide, with little treatment available at the moment to
      alleviate the condition. Memory loss is one of the earliest symptoms associated
      with Alzheimer's disease. The brain regions first affected by pathology include
      the hippocampus, and also the entorhinal cortex and basal cholinergic nuclei
      which project to the hippocampus; importantly, all these areas are required for
      memory formation. Both NGF and BDNF are affected early in the disease and this is
      thought to initiate a cascade of events which exacerbates pathology and leads to
      the symptoms of dementia. This review briefly describes the pathology, symptoms
      and molecular processes associated with Alzheimer's disease; it discusses the
      involvement of the neurotrophins, particularly NGF and BDNF, and their receptors,
      with changes in BDNF considered particularly in the light of its importance in
      synaptic plasticity. In addition, the possibilities of neurotrophin-based
      therapeutics are evaluated.

PMID- 22654717
TI  - Functional multipotency of stem cells: a conceptual review of neurotrophic factor
      based evidence and its role in translational research.
AB  - We here propose an updated concept of stem cells (SCs), with an emphasis on
      neural stem cells (NSCs). The conventional view, which has touched principally on
      the essential property of lineage multipotency (e.g., the ability of NSCs to
      differentiate into all neural cells), should be broadened to include the emerging
      recognition of biofunctional multipotency of SCs to mediate systemic homeostasis,
      evidenced in NSCs in particular by the secretion of neurotrophic factors. Under
      this new conceptual context and taking the NSC as a leading example, one may
      begin to appreciate and seek the "logic" behind the wide range of molecular
      tactics the NSC appears to serve at successive developmental stages as it
      integrates into and prepares, modifies, and guides the surrounding CNS micro- and
      macro-environment towards the formation and self-maintenance of a functioning
      adult nervous system. We suggest that embracing this view of the "multipotency"
      of the SCs is pivotal for correctly, efficiently, and optimally exploiting stem
      cell biology for therapeutic applications, including reconstitution of a
      dysfunctional CNS.

PMID- 22654719
TI  - Chronic stress and Alzheimer's disease-like pathogenesis in a rat model:
      prevention by nicotine.
AB  - Environmental factors including chronic stress may play a critical role in the
      manifestation of Alzheimer's disease (AD).This review summarizes our studies of
      the aggravation of the impaired cognitive ability and its cellular and molecular
      correlates by chronic psychosocial stress and prevention by nicotine in an Abeta
      rat model of AD. We utilized three approaches: learning and memory tests in the
      radial arm water maze, electrophysiological recordings of the cellular correlates
      of memory, long-term potentiation (LTP) and long-term depression (LTD), in
      anesthetized rats, and immunoblot analysis of synaptic plasticity- and cognition
      related signaling molecules. The Abeta rat model, representing the sporadic form
      of established AD, was induced by continuous i.c.v. infusion of a pathogenic dose
      of Abeta peptides via a 14- day osmotic pump. In this AD model, chronic stress
      intensified cognitive deficits, accentuated the disruption of signaling molecules
      levels and produced greater depression of LTP than what was seen with Abeta
      infusion alone. Chronic treatment with nicotine was highly efficient in
      preventing the effects of Abeta infusion and the exacerbating impact of chronic
      stress. Possible mechanisms for the effect of chronic stress are discussed.

PMID- 22654720
TI  - Exploiting the diversity of the heat-shock protein family for primary and
      secondary tauopathy therapeutics.
AB  - The heat shock protein (Hsp) family is an evolutionarily conserved system that is
      charged with preventing unfolded or misfolded proteins in the cell from
      aggregating. In Alzheimer's disease, extracellular accumulation of the amyloid
      beta peptide (Abeta) and intracellular aggregation of the microtubule associated
      protein tau may result from mechanisms involving chaperone proteins like the
      Hsps. Due to the ability of Hsps to regulate aberrantly accumulating proteins
      like Abeta and tau, therapeutic strategies are emerging that target this family
      of chaperones to modulate their pathobiology. This article focuses on the use of
      Hsp-based therapeutics for treating primary and secondary tauopathies like
      Alzheimer's disease. It will particularly focus on the pharmacological targeting
      of the Hsp70/90 system and the value of manipulating Hsp27 for treating
      Alzheimer's disease.

PMID- 22654721
TI  - Recent insights into the involvement of progranulin in frontotemporal dementia.
AB  - Progranulin is a widely expressed protein that is involved in the regulation of
      multiple biological processes, including embryogenesis, host defense, and wound
      repair. In the central nervous system, progranulin is constitutively expressed at
      modest levels in neurons and microglia, but shows dramatic microglial
      immunoreactivity in degenerative diseases that exhibit prominent
      neuroinflammation. In addition to the role that PGRN plays in the periphery, its
      expression is of critical importance in brain health, as demonstrated by recent
      discovery that progranulin haploinsufficiency results in familial frontotemporal
      lobar degeneration. Since progranulin deficiency was first described, there has
      been an intense ongoing effort to decipher the mysterious role that this protein
      plays in dementia. This review provides an update on our understanding of the
      possible neuronal function and discusses the challenging problems related to
      progranulin expression within genetics, cell biology, and neurodegeneration.

PMID- 22654722
TI  - Impact and Therapeutic Potential of PPARs in Alzheimer's Disease.
AB  - Peroxisome proliferator activated receptors (PPARs) are well studied for their
      role of peripheral metabolism, but they also may be involved in the pathogenesis
      of various disorders of the central nervous system (CNS) including multiple
      sclerosis, amyotrophic lateral sclerosis, Alzheimer's and, Parkinson's disease.
      The observation that PPARs are able to suppress the inflammatory response in
      peripheral macrophages and in several models of human autoimmune diseases, lead
      to the idea that PPARs might be beneficial for CNS disorders possessing an
      inflammatory component. The neuroinflammatory response during the course of
      Alzheimer's disease (AD) is triggered by the deposition of the beta-amyloid
      peptide in extracellular plaques and ongoing neurodegeneration. Non-steroidal
      anti-inflammatory drugs (NSAIDs) have been considered to delay the onset and
      reduce the risk to develop Alzheimer's disease, while they also directly activate
      PPARgamma. This led to the hypothesis that NSAID protection in AD may be partly
      mediated by PPARgamma. Several lines of evidence have supported this hypothesis,
      using AD related transgenic cellular and animal models. Stimulation of PPARgamma
      by synthetic agonist (thiazolidinediones) inducing anti-inflammatory, anti
      amyloidogenic and insulin sensitizing effects may account for the observed
      effects. Several clinical trials already revealed promising results using
      PPARgamma agonists, therefore PPARgamma represents an attractive therapeutic
      target for the treatment of AD.

PMID- 22654723
TI  - Therapeutic interventions targeting Beta amyloid pathogenesis in an aging dog
      model.
AB  - Aged dogs and humans share complex cognitive and pathological responses to aging.
      Specifically, dogs develop Alzheimer's Disease (AD) like beta-amyloid (Abeta)
      that are associated with cognitive deficits. Currently, therapeutic approaches to
      prevent AD are targeted towards reduced production, aggregation and increased
      clearance of Abeta. The current review discusses cognition and neuropathology of
      the aging canine model and how it has and continues to be useful in further
      understanding the safety and efficacy of potential AD prevention therapies
      targeting Abeta.

PMID- 22654724
TI  - Neuronal and vascular oxidative stress in Alzheimer's disease.
AB  - The brain is a highly metabolically active organ producing large amounts of
      reactive oxygen species (ROS). These ROS are kept in check by an elaborate
      network of antioxidants. Although ROS are necessary for signaling and synaptic
      plasticity, their uncontrolled levels cause oxidation of essential macromolecules
      such as membrane lipids, nucleic acids, enzymes and cytoskeletal proteins.
      Indeed, overproduction of ROS and/or failure of the antioxidant network lead to
      neuronal oxidative stress, a condition associated with not only aging but also
      Alzheimer's disease (AD). However, the specific source of excessive ROS
      production has not yet been identified. On one hand, amyloid beta (Abeta) has
      been extensively shown to act as an oxidant molecule. On the other hand,
      oxidative stress has been shown to precede and exacerbate Abeta pathology. This
      review will address the involvement of oxidative stress in the context of
      neuronal as well as vascular dysfunction associated with AD.

PMID- 22654725
TI  - Alzheimer's disease: pathological mechanisms and recent insights.
AB  - Amyloidopathies cause neurodegeneration in a substantial portion of the elderly
      population. Improvements in long term health care have made elderly individuals a
      large and growing demographic group, marking these diseases as a major public
      health concern. Alzheimer's Disease (AD) is the most studied form of
      neurodegenerative amyloidopathy. Although our understanding of AD is far from
      complete, several decades of research have advanced our knowledge to the point
      where it is conceivable that some form of disease modifying therapy may be
      available in the near future. These advances have been built on a strong
      mechanistic understanding of the disease from its underlying genetics, molecular
      biology and clinical pathology. Insights derived from the study of other
      neurodegenerative diseases, such as some forms of frontotemporal dementia, have
      been critical to this process. This knowledge has allowed researchers to
      construct animal models of the disease process that have paved the way towards
      the development of therapeutics. However, what was once thought to be a
      straightforward problem has evolved into a series of disappointing outcomes.
      Examination of pathways common to all neurodegenerative diseases, including the
      cellular mechanisms that clear misfolded proteins and their regulation, may be
      the best way to move forward.

PMID- 22654726
TI  - A role for calcineurin in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an incurable age-related neurodegenerative disorder
      characterized by profound memory dysfunction. This bellwether symptom suggests
      involvement of the hippocampus -- a brain region responsible for memory formation
      -- and coincidentally an area heavily burdened by hyperphosphorylated tau and
      neuritic plaques of amyloid beta (Abeta). Recent evidence suggests that pre
      fibrillar soluble Abeta underlies an early, progressive loss of synapses that is
      a hallmark of AD. One of the downstream effects of soluble Abeta aggregates is
      the activation of the phosphatase calcineurin (CaN). This review details the
      evidence of CaN hyperactivity in 'normal' aging, models of AD, and actual disease
      pathogenesis; elaborates on how this could manifest as memory impairment,
      neuroinflammation, hyperphosphorylated tau, and neuronal death.

PMID- 22654727
TI  - Consequences of Aberrant Insulin Regulation in the Brain: Can Treating Diabetes
      be Effective for Alzheimer's Disease.
AB  - There is an urgent need for new ways to treat Alzheimer's disease (AD), the most
      common cause of dementia in the elderly. Current therapies are modestly effective
      at treating the symptoms, and do not significantly alter the course of the
      disease. Over the years, a range of epidemiological and experimental studies have
      demonstrated interactions between diabetes mellitus and AD. As both diseases are
      leading causes of morbidity and mortality in the elderly and are frequent co
      morbid conditions, it has raised the possibility that treating diabetes might be
      effective in slowing AD. This is currently being attempted with drugs such as the
      insulin sensitizer rosiglitazone. These two diseases share many clinical and
      biochemical features, such as elevated oxidative stress, vascular dysfunction,
      amyloidogenesis and impaired glucose metabolism suggesting common pathogenic
      mechanisms. The main thrust of this review will be to explore the evidence from a
      pathological point of view to determine whether diabetes can cause or exacerbate
      AD. This was supported by a number of animal models of AD that have been shown to
      have enhanced pathology when diabetic conditions were induced. The one drawback
      in linking diabetes and insulin to AD has been the postmortem studies of diabetic
      brains demonstrating that AD pathology was not increased; in fact decreased
      pathology has often been reported. In addition, diabetes induces its own distinct
      features of neuropathology different from AD. There are common pathological
      features to be considered including vascular abnormalities, a major feature
      arising from diabetes; there is increasing evidence that vascular abnormalities
      can contribute to AD. The most important common mechanism between insulin
      resistant (type II) diabetes and AD could be impaired insulin signaling; a form
      of toxic amyloid can damage neuronal insulin receptors and affect insulin
      signaling and cell survival. It has even been suggested that AD could be
      considered as "type 3 diabetes" since insulin can be produced in brain. Another
      common feature of diabetes and AD are increased advanced glycation endproduct
      modified proteins are found in diabetes and in the AD brain; the receptor for
      advanced glycation endproducts plays a prominent role in both diseases. In
      addition, a major role for insulin degrading enzyme in the degradation of Abeta
      peptide has been identified. Although clinical trials of certain types of
      diabetic medications for treatment of AD have been conducted, further
      understanding the common pathological processes of diabetes and AD are needed to
      determine whether these diseases share common therapeutic targets.

PMID- 22654728
TI  - Emerging Pharmacological Properties of Cholinergic Synaptic Transmission:
      Comparison between Mammalian and Insect Synaptic and Extrasynaptic Nicotinic
      Receptors.
AB  - Acetylcholine (ACh) is probably the oldest signalling neurotransmitter which
      appeared in evolution before the nervous system. It is present in bacteria,
      algae, protozoa and plants. In insects and mammals it is involved in cell-to-cell
      communications in various neuronal and non-neuronal tissues. The discovery of
      nicotinic acetylcholine receptors (nAChRs) as the main receptors involved in
      rapid cholinergic neurotransmission has helped to understand the role of ACh at
      synaptic level. Recently, several lines of evidence have indicated that
      extrasynaptically expressed nAChRs display distinct pharmacological properties
      from the ones expressed at synaptic level. The role of both nAChRs at insect
      extrasynaptic and/or synaptic levels has been underestimated due to the lack of
      pharmacological tools to identify different nicotinic receptor subtypes. In the
      present review, we summarize recent electrophysiological and pharmacological
      studies on the extrasynaptic and synaptic differences between insect and
      mammalian nAChR subtypes and we discuss on the pharmacological impact of several
      drugs such as neonicotinoid insecticides targeting these receptors. In fact,
      nAChRs are involved in a wide range of pathophysiological processes such as
      epilepsy, pain and a wide range of neurodegenerative and psychiatric disorders.
      In addition, they are the target sites of neonicotinoid insecticides which are
      known to act as nicotinic agonists causing severe poisoning in insects and
      mammals.

PMID- 22654729
TI  - cGMP Signaling, Phosphodiesterases and Major Depressive Disorder.
AB  - DEFICITS IN NEUROPLASTICITY ARE HYPOTHESIZED TO UNDERLIE THE PATHOPHYSIOLOGY OF
      MAJOR DEPRESSIVE DISORDER (MDD): the effectiveness of antidepressants is thought
      to be related to the normalization of disrupted synaptic transmission and
      neurogenesis. The cyclic adenosine monophosphate (cAMP) signaling cascade has
      received considerable attention for its role in neuroplasticity and MDD. However
      components of a closely related pathway, the cyclic guanosine monophosphate
      (cGMP) have been studied with much lower intensity, even though this signaling
      transduction cascade is also expressed in the brain and the activity of this
      pathway has been implicated in learning and memory processes. Cyclic GMP acts as
      a second messenger; it amplifies signals received at postsynaptic receptors and
      activates downstream effector molecules resulting in gene expression changes and
      neuronal responses. Phosphodiesterase (PDE) enzymes degrade cGMP into 5'GMP and
      therefore they are involved in the regulation of intracellular levels of cGMP.
      Here we review a growing body of evidence suggesting that the cGMP signaling
      cascade warrants further investigation for its involvement in MDD and
      antidepressant action.

PMID- 22654732
TI  - The Imaging and Cognition Genetics Conference 2011, ICG 2011: A Meeting of Minds.
AB  - In June 2011, 70 researchers from the disciplines of cognitive science, genetics,
      psychology, psychiatry, neurobiology, and computer science gathered in Os,
      Norway, for the first Imaging and Cognition Genetics meeting. The aim of the
      conference was to discuss progress, enhance collaboration, and maximize the
      sharing of resources within this new field. In this Perspective, we summarize the
      major themes that emerged from ICG 2011. The first is the importance of defining
      cognitive and imaging phenotypes and endophenotypes suitable for genetic
      analysis. These can come from differential psychology, cognitive science,
      structural MRI, tractography, and functional imaging. The second theme is the
      emergence of new methods for the analysis of complex traits. These include
      advanced computational and statistical techniques for analyzing complex datasets,
      and new ways of interpreting data from genome-wide association studies, such as
      jointly evaluating the contribution of SNPs in specific genes and pathways rather
      than considering single SNPs in isolation. The final theme is the importance of
      establishing functional correlates of newly identified genetic variants.

PMID- 22654730
TI  - Building Bridges between Perceptual and Economic Decision-Making: Neural and
      Computational Mechanisms.
AB  - Investigation into the neural and computational bases of decision-making has
      proceeded in two parallel but distinct streams. Perceptual decision-making (PDM)
      is concerned with how observers detect, discriminate, and categorize noisy
      sensory information. Economic decision-making (EDM) explores how options are
      selected on the basis of their reinforcement history. Traditionally, the sub
      fields of PDM and EDM have employed different paradigms, proposed different
      mechanistic models, explored different brain regions, disagreed about whether
      decisions approach optimality. Nevertheless, we argue that there is a common
      framework for understanding decisions made in both tasks, under which an agent
      has to combine sensory information (what is the stimulus) with value information
      (what is it worth). We review computational models of the decision process
      typically used in PDM, based around the idea that decisions involve a serial
      integration of evidence, and assess their applicability to decisions between good
      and gambles. Subsequently, we consider the contribution of three key brain
      regions - the parietal cortex, the basal ganglia, and the orbitofrontal cortex
      (OFC) - to perceptual and EDM, with a focus on the mechanisms by which sensory
      and reward information are integrated during choice. We find that although the
      parietal cortex is often implicated in the integration of sensory evidence, there
      is evidence for its role in encoding the expected value of a decision. Similarly,
      although much research has emphasized the role of the striatum and OFC in value
      guided choices, they may play an important role in categorization of perceptual
      information. In conclusion, we consider how findings from the two fields might be
      brought together, in order to move toward a general framework for understanding
      decision-making in humans and other primates.

PMID- 22654731
TI  - Molecular regionalization of the diencephalon.
AB  - The anatomic complexity of the diencephalon depends on precise molecular and
      cellular regulative mechanisms orchestrated by regional morphogenetic organizers
      at the neural tube stage. In the diencephalon, like in other neural tube regions,
      dorsal and ventral signals codify positional information to specify ventro-dorsal
      regionalization. Retinoic acid, Fgf8, BMPs, and Wnts signals are the molecular
      factors acting upon the diencephalic epithelium to specify dorsal structures,
      while Shh is the main ventralizing signal. A central diencephalic organizer, the
      zona limitans intrathalamica (ZLI), appears after neurulation in the central
      diencephalic alar plate, establishing additional antero-posterior positional
      information inside diencephalic alar plate. Based on Shh expression, the ZLI acts
      as a morphogenetic center, which cooperates with other signals in thalamic
      specification and pattering in the alar plate of diencephalon. Indeed, Shh is
      expressed first in the basal plate extending dorsally through the ZLI epithelium
      as the development proceeds. Despite the importance of ZLI in diencephalic
      morphogenesis the mechanisms that regulate its development remain incompletely
      understood. Actually, controversial interpretations in different experimental
      models have been proposed. That is, experimental results have suggested that (i)
      the juxtaposition of the molecularly heterogeneous neuroepithelial areas, (ii)
      cell reorganization in the epithelium, and/or (iii) planar and vertical
      inductions in the neural epithelium, are required for ZLI specification and
      development. We will review some experimental data to approach the study of the
      molecular regulation of diencephalic regionalization, with special interest in
      the cellular mechanisms underlying planar inductions.

PMID- 22654733
TI  - The Tale of the Three Brothers - Shh, Wnt, and Fgf during Development of the
      Thalamus.
AB  - The thalamic complex is an essential part of the brain that requires a
      combination of specialized activities to attain its final complexity. In the
      following review we will describe the induction process of the mid-diencephalic
      organizer (MDO) where three different signaling pathways merge: Wnt, Shh, and
      Fgf. Here, we dissect the function of each signaling pathway in the thalamus in
      chronological order of their appearance. First we describe the Wnt mediated
      induction of the MDO and compartition of the caudal forebrain, then the Shh
      mediated determination of proneural gene expression before discussing recent
      progress in characterizing Fgf function during thalamus development. Then, we
      focus on transcription factors, which are regulated by these pathways and which
      play a pivotal role in neurogenesis in the thalamus. The three signaling pathways
      act together in a strictly regulated chronology to orchestrate the development of
      the entire thalamus.

PMID- 22654735
TI  - A model combining oscillations and attractor dynamics for generation of grid cell
      firing.
AB  - Different models have been able to account for different features of the data on
      grid cell firing properties, including the relationship of grid cells to cellular
      properties and network oscillations. This paper describes a model that combines
      elements of two major classes of models of grid cells: models using interactions
      of oscillations and models using attractor dynamics. This model includes a
      population of units with oscillatory input representing input from the medial
      septum. These units are termed heading angle cells because their connectivity
      depends upon heading angle in the environment as well as the spatial phase coded
      by the cell. These cells project to a population of grid cells. The sum of the
      heading angle input results in standing waves of circularly symmetric input to
      the grid cell population. Feedback from the grid cell population increases the
      activity of subsets of the heading angle cells, resulting in the network settling
      into activity patterns that resemble the patterns of firing fields in a
      population of grid cells. The properties of heading angle cells firing as
      conjunctive grid-by-head-direction cells can shift the grid cell firing according
      to movement velocity. The pattern of interaction of oscillations requires use of
      separate populations that fire on alternate cycles of the net theta rhythmic
      input to grid cells.

PMID- 22654734
TI  - Inhibitory Regulation of Dendritic Activity in vivo.
AB  - The spatiotemporal control of neuronal excitability is fundamental to the
      inhibitory process. We now have a wealth of information about the active
      dendritic properties of cortical neurons including axonally generated sodium
      action potentials as well as local sodium spikelets generated in the dendrites,
      calcium plateau spikes, and NMDA spikes. All of these events have been shown to
      be highly modified by the spatiotemporal pattern of nearby inhibitory input which
      can drastically change the output firing mode of the neuron. This means that
      particular populations of interneurons embedded in the neocortical microcircuitry
      can more precisely control pyramidal cell output than has previously been
      thought. Furthermore, the output of any given neuron tends to feed back onto
      inhibitory circuits making the resultant network activity further dependent on
      inhibition. Network activity is therefore ultimately governed by the subcellular
      microcircuitry of the cortex and it is impossible to ignore the
      subcompartmentalization of inhibitory influence at the neuronal level in order to
      understand its effects at the network level. In this article, we summarize the
      inhibitory circuits that have been shown so far to act on specific dendritic
      compartments in vivo.

PMID- 22654736
TI  - Expression of mitochondrial branched-chain aminotransferase and alpha-keto-acid
      dehydrogenase in rat brain: implications for neurotransmitter metabolism.
AB  - In the brain, metabolism of the essential branched chain amino acids (BCAAs)
      leucine, isoleucine, and valine, is regulated in part by protein synthesis
      requirements. Excess BCAAs are catabolized or excreted. The first step in BCAA
      catabolism is catalyzed by the branched chain aminotransferase (BCAT) isozymes,
      mitochondrial BCATm and cytosolic BCATc. A product of this reaction, glutamate,
      is the major excitatory neurotransmitter and precursor of the major inhibitory
      neurotransmitter gamma-aminobutyric acid (GABA). The BCATs are thought to
      participate in a alpha-keto-acid nitrogen shuttle that provides nitrogen for
      synthesis of glutamate from alpha-ketoglutarate. The branched-chain alpha-keto
      acid dehydrogenase enzyme complex (BCKDC) catalyzes the second, irreversible step
      in BCAA metabolism, which is oxidative decarboxylation of the branched-chain
      alpha-keto acid (BCKA) products of the BCAT reaction. Maple Syrup Urine Disease
      (MSUD) results from genetic defects in BCKDC, which leads to accumulation of
      toxic levels of BCAAs and BCKAs that result in brain swelling. Immunolocalization
      of BCATm and BCKDC in rats revealed that BCATm is present in astrocytes in white
      matter and in neuropil, while BCKDC is expressed only in neurons. BCATm appears
      uniformly distributed in astrocyte cell bodies throughout the brain. The
      segregation of BCATm to astrocytes and BCKDC to neurons provides further support
      for the existence of a BCAA-dependent glial-neuronal nitrogen shuttle since the
      data show that BCKAs produced by glial BCATm must be exported to neurons.
      Additionally, the neuronal localization of BCKDC suggests that MSUD is a neuronal
      defect involving insufficient oxidation of BCKAs, with secondary effects
      extending beyond the neuron.

PMID- 22654737
TI  - Transcranial alternating current stimulation affects decision making.

PMID- 22654738
TI  - Neural plasticity expressed in central auditory structures with and without
      tinnitus.
AB  - Sensory training therapies for tinnitus are based on the assumption that,
      notwithstanding neural changes related to tinnitus, auditory training can alter
      the response properties of neurons in auditory pathways. To assess this
      assumption, we investigated whether brain changes induced by sensory training in
      tinnitus sufferers and measured by electroencephalography (EEG) are similar to
      those induced in age and hearing loss matched individuals without tinnitus
      trained on the same auditory task. Auditory training was given using a 5 kHz 40
      Hz amplitude-modulated (AM) sound that was in the tinnitus frequency region of
      the tinnitus subjects and enabled extraction of the 40-Hz auditory steady-state
      response (ASSR) and P2 transient response known to localize to primary and non
      primary auditory cortex, respectively. P2 amplitude increased over training
      sessions equally in participants with tinnitus and in control subjects,
      suggesting normal remodeling of non-primary auditory regions in tinnitus.
      However, training-induced changes in the ASSR differed between the tinnitus and
      control groups. In controls the phase delay between the 40-Hz response and
      stimulus waveforms reduced by about 10 degrees  over training, in agreement with
      previous results obtained in young normal hearing individuals. However, ASSR
      phase did not change significantly with training in the tinnitus group, although
      some participants showed phase shifts resembling controls. On the other hand,
      ASSR amplitude increased with training in the tinnitus group, whereas in controls
      this response (which is difficult to remodel in young normal hearing subjects)
      did not change with training. These results suggest that neural changes related
      to tinnitus altered how neural plasticity was expressed in the region of primary
      but not non-primary auditory cortex. Auditory training did not reduce tinnitus
      loudness although a small effect on the tinnitus spectrum was detected.

PMID- 22654739
TI  - Resequencing of the auxiliary GABA(B) receptor subunit gene KCTD12 in chronic
      tinnitus.
AB  - Tinnitus is a common and often incapacitating hearing disorder marked by the
      perception of phantom sounds. Susceptibility factors remain largely unknown but
      GABA(B) receptor signaling has long been implicated in the response to treatment
      and, putatively, in the etiology of the disorder. We hypothesized that variation
      in KCTD12, the gene encoding an auxiliary subunit of GABA(B) receptors, could
      help to predict the risk of developing tinnitus. Ninety-five Caucasian
      outpatients with a diagnosis of chronic tinnitus were systematically screened for
      mutations in the KCTD12 open reading frame and the adjacent 3' untranslated
      region by Sanger sequencing. Allele frequencies were determined for 14 known
      variants of which three (rs73237446, rs34544607, and rs41287030) were
      polymorphic. When allele frequencies were compared to data from a large reference
      population of European ancestry, rs34544607 was associated with tinnitus (p =
      0.04). However, KCTD12 genotype did not predict tinnitus severity (p = 0.52) and
      the association with rs34544607 was weakened after screening 50 additional cases
      (p = 0.07). Pending replication in a larger cohort, KCTD12 may act as a risk
      modifier in chronic tinnitus. Issues that are yet to be addressed include the
      effects of neighboring variants, e.g., in the KCTD12 gene regulatory region, plus
      interactions with variants of GABA(B1) and GABA(B2).

PMID- 22654740
TI  - Integrative role of the histaminergic system in feeding and taste perception.
AB  - Feeding behavior is regulated by a complex interplay of many endogenous
      substances, such as peptides and neurotransmitters in the central nervous system.
      Histamine is a neurotransmitter which expresses an anorectic effect on food
      intake via histamine H(1) receptors. The histaminergic system exists downstream
      of leptin, a satiety factor secreted from white adipose tissue. Because direct
      stimulation of the histaminergic system by histamine H(3)-inverse agonists or
      antagonists can normalize the obese phenotype in which animal models with
      exogenous leptin resistance, which resembles human obesity, the potential roles
      of histamine H(3) receptors as a therapeutic target now draw attention.
      Histaminergic activity is enhanced during feeding, and an oral somatic sensation
      is thought to affect histaminergic activity while blood glucose levels do not. In
      addition, gustatory information can modulate histaminergic activity by two
      mechanisms: by physiological excitation of the chorda tympani nerve, one of the
      taste nerves and by emotions elicited by taste perception, i.e., taste
      palatability. Particularly, aversive and hazardous taste stimuli tonically
      facilitate histaminergic activity, suggesting that the histaminergic system is
      involved in the response to harmful stimuli. Together with recent findings, it is
      postulated that the histaminergic system responds to both mechanical and chemical
      sensory input from the oral cavity during feeding and is exerted as a part of the
      danger response system.

PMID- 22654741
TI  - Learning-facilitated long-term depression and long-term potentiation at mossy
      fiber-CA3 synapses requires activation of beta-adrenergic receptors.
AB  - Learning-facilitated plasticity refers to hippocampal synaptic plasticity that is
      facilitated by novel spatial learning events. Both long-term potentiation (LTP)
      and long-term depression (LTD) are facilitated by novel hippocampus-dependent
      learning. This has important ramifications for our understanding of how the
      hippocampus encodes memory. One structure that is rarely studied in vivo, but is
      believed to be crucially important for working and long-term memory processing is
      the hippocampal CA3 region. Whereas learning-facilitated plasticity has been
      described in this structure, the mechanisms underlying this phenomenon have not
      been explored. The noradrenergic system plays an important role in arousal and
      qualification of new information as salient. It regulates synaptic plasticity in
      the dentate gyrus and CA1, but nothing is known about the regulation by the
      noradrenergic system of synaptic plasticity in the CA3 region. We explored
      whether beta-adrenergic receptors contribute to learning-facilitated plasticity
      at mossy fiber (mf)-CA3 synapses of behaving rats. We found that receptor
      antagonism had no effect on basal synaptic transmission, short-term potentiation
      (STP), short-term depression, LTP, or LTD, that were electrically induced by
      patterned afferent stimulation. We found, however, that both learning-facilitated
      LTP and LTD were prevented by antagonism of beta-adrenergic receptors, whereas
      the agonist isoproterenol facilitated STP into LTP. Thus, learning-facilitated
      and electrically-induced plasticity may not share the same prerequisites. These
      results support that the mf synapse engages in a distinct aspect of encoding of
      spatial information that involves both LTP and LTD. Furthermore, changes in
      arousal that are coupled to new learning are associated with activation of
      hippocampal beta-adrenergic receptors that in turn comprise a key element in this
      type of information acquisition and processing by the CA3 region.

PMID- 22654742
TI  - Modulation of tactile duration judgments by emotional pictures.
AB  - Judging the duration of emotional stimuli is known to be influenced by their
      valence and arousal values. However, whether and how perceiving emotion in one
      modality affects time perception in another modality is still unclear. To
      investigate this, we compared the influence of different types of emotional
      pictures-a picture of threat, disgust, or a neutral picture presented at the
      start of a trial-on temporal bisection judgments of the duration of a
      subsequently presented vibrotactile stimulus. We found an overestimation of
      tactile duration following exposure to pictures of threat, but not pictures of
      disgust (even though these scored equally high on arousal), in a short-range
      temporal bisection task (range 300/900 ms). Follow-up experiments revealed that
      this duration lengthening effect was abolished when the range to be bisected was
      increased (1000/1900 ms). However, duration overestimation was maintained in the
      short-range bisection task regardless of whether the interval between the visual
      and tactile events was short or long. This pattern is inconsistent with a general
      arousal interpretation of duration distortion and suggests that crossmodal
      linkages in the processing of emotions and emotional regulation are two main
      factors underlying the manifestation of crossmodal duration modulation.

PMID- 22654743
TI  - Neuroimaging evidence for cannabinoid modulation of cognition and affect in man.

PMID- 22654744
TI  - Selective wheat germ agglutinin (WGA) uptake in the hippocampus from the locus
      coeruleus of dopamine-beta-hydroxylase-WGA transgenic mice.
AB  - We generated transgenic mice in which a trans-synaptic tracer, wheat germ
      agglutinin (WGA), was specifically expressed in the locus coeruleus (LC) neurons
      under the control of the dopamine-beta-hydroxylase (DBH) gene promoter. WGA
      protein was produced in more than 95% of the tyrosine hydroxylase (TH)-positive
      LC neurons sampled. Transynaptic transfer of WGA was most evident in CA3 neurons
      of the hippocampus, but appeared absent in CA1 neurons. Faint but significant WGA
      immunoreactivity was observed surrounding the nuclei of dentate granule cells.
      Putative hilar mossy cells, identified by the presence of calretinin in the
      ventral hippocampus, appeared uniformly positive for transynaptically transferred
      WGA protein. GAD67-positive interneurons in the hilar and CA3 regions tended to
      be WGA-positive, although a subset of them did not show WGA co-localization. The
      same mixed WGA uptake profile was apparent when examining co-localization with
      parvalbumin. The selective uptake of WGA by dentate granule cells, mossy cells,
      and CA3 pyramidal neurons is consistent with evidence for a large proportion of
      conventional synapses adjacent to LC axonal varicosities in these regions. The
      lack of WGA uptake in the CA1 region and its relatively sparse innervation by DBH
      positive fibers suggest that a majority of the TH-positive classical synapses
      revealed by electron microscopy in that region may be producing dopamine. The
      overall pattern of WGA uptake in these transgenic mice implies a selective role
      for the granule cell-mossy cell-CA3 network in processing novelty or the salient
      environmental contingency changes signaled by LC activity.

PMID- 22654745
TI  - Neurobiology of schizophrenia: search for the elusive correlation with symptoms.
AB  - In the last half-century, human neuroscience methods provided a way to study
      schizophrenia in vivo, and established that it is associated with subtle
      abnormalities in brain structure and function. However, efforts to understand the
      neurobiological bases of the clinical symptoms that the diagnosis is based on
      have been largely unsuccessful. In this paper, we provide an overview of the
      conceptual and methodological obstacles that undermine efforts to link the
      severity of specific symptoms to specific neurobiological measures. These
      obstacles include small samples, questionable reliability and validity of
      measurements, medication confounds, failure to distinguish state and trait
      effects, correlation-causation ambiguity, and the absence of compelling animal
      models of specific symptoms to test mechanistic hypotheses derived from brain
      symptom correlations. We conclude with recommendations to promote progress in
      establishing brain-symptom relationships.

PMID- 22654746
TI  - Working memory related brain network connectivity in individuals with
      schizophrenia and their siblings.
AB  - A growing number of studies have reported altered functional connectivity in
      schizophrenia during putatively "task-free" states and during the performance of
      cognitive tasks. However, there have been few systematic examinations of
      functional connectivity in schizophrenia across rest and different task states to
      assess the degree to which altered functional connectivity reflects a stable
      characteristic or whether connectivity changes vary as a function of task
      demands. We assessed functional connectivity during rest and during three working
      memory loads of an N-back task (0-back, 1-back, 2-back) among: (1) individuals
      with schizophrenia (N = 19); (2) the siblings of individuals with schizophrenia
      (N = 28); (3) healthy controls (N = 10); and (4) the siblings of healthy controls
      (N = 17). We examined connectivity within and between four brain networks: (1)
      frontal-parietal (FP); (2) cingulo-opercular (CO); (3) cerebellar (CER); and (4)
      default mode (DMN). In terms of within-network connectivity, we found that
      connectivity within the DMN and FP increased significantly between resting state
      and 0-back, while connectivity within the CO and CER decreased significantly
      between resting state and 0-back. Additionally, we found that connectivity within
      both the DMN and FP was further modulated by memory load. In terms of between
      network connectivity, we found that the DMN became significantly more "anti
      correlated" with the FP, CO, and CER networks during 0-back as compared to rest,
      and that connectivity between the FP and both CO and CER networks increased with
      memory load. Individuals with schizophrenia and their siblings showed consistent
      reductions in connectivity between both the FP and CO networks with the CER
      network, a finding that was similar in magnitude across rest and all levels of
      working memory load. These findings are consistent with the hypothesis that
      altered functional connectivity in schizophrenia reflects a stable characteristic
      that is present across cognitive states.

PMID- 22654747
TI  - Social attention with real versus reel stimuli: toward an empirical approach to
      concerns about ecological validity.
AB  - Cognitive neuroscientists often study social cognition by using simple but
      socially relevant stimuli, such as schematic faces or images of other people.
      Whilst this research is valuable, important aspects of genuine social encounters
      are absent from these studies, a fact that has recently drawn criticism. In the
      present review we argue for an empirical approach to the determination of the
      equivalence of different social stimuli. This approach involves the systematic
      comparison of different types of social stimuli ranging in their approximation to
      a real social interaction. In garnering support for this cognitive ethological
      approach, we focus on recent research in social attention that has involved
      stimuli ranging from simple schematic faces to real social interactions. We
      highlight both meaningful similarities and differences in various social
      attentional phenomena across these different types of social stimuli thus
      validating the utility of the research initiative. Furthermore, we argue that
      exploring these similarities and differences will provide new insights into
      social cognition and social neuroscience.

PMID- 22654748
TI  - Repetitive tactile stimulation changes resting-state functional connectivity
      implications for treatment of sensorimotor decline.
AB  - Neurological disorders and physiological aging can lead to a decline of
      perceptual abilities. In contrast to the conventional therapeutic approach that
      comprises intensive training and practicing, passive repetitive sensory
      stimulation (RSS) has recently gained increasing attention as an alternative to
      countervail the sensory decline by improving perceptual abilities without the
      need of active participation. A particularly effective type of high-frequency
      RSS, utilizing Hebbian learning principles, improves perceptual acuity as well as
      sensorimotor functions and has been successfully applied to treat chronic stroke
      patients and elderly subjects. High-frequency RSS has been shown to induce
      plastic changes of somatosensory cortex such as representational map
      reorganization, but its impact on the brain's ongoing network activity and
      resting-state functional connectivity has not been investigated so far. Here, we
      applied high-frequency RSS in healthy human subjects and analyzed resting state
      Electroencephalography (EEG) functional connectivity patterns before and after
      RSS by means of imaginary coherency (ImCoh), a frequency-specific connectivity
      measure which is known to reduce over-estimation biases due to volume conduction
      and common reference. Thirty minutes of passive high-frequency RSS lead to
      significant ImCoh-changes of the resting state mu-rhythm in the individual upper
      alpha frequency band within distributed sensory and motor cortical areas. These
      stimulation induced distributed functional connectivity changes likely underlie
      the previously observed improvement in sensorimotor integration.

PMID- 22654750
TI  - The role of pulvinar in the transmission of information in the visual hierarchy.
AB  - VISUAL RECEPTIVE FIELD (RF) ATTRIBUTES IN VISUAL CORTEX OF PRIMATES HAVE BEEN
      EXPLAINED MAINLY FROM CORTICAL CONNECTIONS: visual RFs progress from simple to
      complex through cortico-cortical pathways from lower to higher levels in the
      visual hierarchy. This feedforward flow of information is paired with top-down
      processes through the feedback pathway. Although the hierarchical organization
      explains the spatial properties of RFs, is unclear how a non-linear transmission
      of activity through the visual hierarchy can yield smooth contrast response
      functions in all level of the hierarchy. Depending on the gain, non-linear
      transfer functions create either a bimodal response to contrast, or no contrast
      dependence of the response in the highest level of the hierarchy. One possible
      mechanism to regulate this transmission of visual contrast information from low
      to high level involves an external component that shortcuts the flow of
      information through the hierarchy. A candidate for this shortcut is the Pulvinar
      nucleus of the thalamus. To investigate representation of stimulus contrast a
      hierarchical model network of ten cortical areas is examined. In each level of
      the network, the activity from the previous layer is integrated and then non
      linearly transmitted to the next level. The arrangement of interactions creates a
      gradient from simple to complex RFs of increasing size as one moves from lower to
      higher cortical levels. The visual input is modeled as a Gaussian random input,
      whose width codes for the contrast. This input is applied to the first area. The
      output activity ratio among different contrast values is analyzed for the last
      level to observe sensitivity to a contrast and contrast invariant tuning. For a
      purely cortical system, the output of the last area can be approximately contrast
      invariant, but the sensitivity to contrast is poor. To account for an alternative
      visual processing pathway, non-reciprocal connections from and to a parallel
      pulvinar like structure of nine areas is coupled to the system. Compared to the
      pure feedforward model, cortico-pulvino-cortical output presents much more
      sensitivity to contrast and has a similar level of contrast invariance of the
      tuning.

PMID- 22654751
TI  - Fluctuating inhibitory inputs promote reliable spiking at theta frequencies in
      hippocampal interneurons.
AB  - Theta-frequency (4-12 Hz) rhythms in the hippocampus play important roles in
      learning and memory. CA1 interneurons located at the stratum lacunosum-moleculare
      and radiatum junction (LM/RAD) are thought to contribute to hippocampal theta
      population activities by rhythmically pacing pyramidal cells with inhibitory
      postsynaptic potentials. This implies that LM/RAD cells need to fire reliably at
      theta frequencies in vivo. To determine whether this could occur, we use
      biophysically based LM/RAD model cells and apply different cholinergic and
      synaptic inputs to simulate in vivo-like network environments. We assess spike
      reliabilities and spiking frequencies, identifying biophysical properties and
      network conditions that best promote reliable theta spiking. We find that
      synaptic background activities that feature large inhibitory, but not excitatory,
      fluctuations are essential. This suggests that strong inhibitory input to these
      cells is vital for them to be able to contribute to population theta activities.
      Furthermore, we find that Type I-like oscillator models produced by augmented
      persistent sodium currents (I(NaP)) or diminished A-type potassium currents
      (I(A)) enhance reliable spiking at lower theta frequencies. These Type I-like
      models are also the most responsive to large inhibitory fluctuations and can fire
      more reliably under such conditions. In previous work, we showed that I(NaP) and
      I(A) are largely responsible for establishing LM/RAD cells' subthreshold
      activities. Taken together with this study, we see that while both these currents
      are important for subthreshold theta fluctuations and reliable theta spiking,
      they contribute in different ways - I(NaP) to reliable theta spiking and
      subthreshold activity generation, and I(A) to subthreshold activities at theta
      frequencies. This suggests that linking subthreshold and suprathreshold
      activities should be done with consideration of both in vivo contexts and
      biophysical specifics.

PMID- 22654752
TI  - PyXNAT: XNAT in Python.
AB  - As neuroimaging databases grow in size and complexity, the time researchers spend
      investigating and managing the data increases to the expense of data analysis. As
      a result, investigators rely more and more heavily on scripting using high-level
      languages to automate data management and processing tasks. For this, a
      structured and programmatic access to the data store is necessary. Web services
      are a first step toward this goal. They however lack in functionality and ease of
      use because they provide only low-level interfaces to databases. We introduce
      here PyXNAT, a Python module that interacts with The Extensible Neuroimaging
      Archive Toolkit (XNAT) through native Python calls across multiple operating
      systems. The choice of Python enables PyXNAT to expose the XNAT Web Services and
      unify their features with a higher level and more expressive language. PyXNAT
      provides XNAT users direct access to all the scientific packages in Python.
      Finally PyXNAT aims to be efficient and easy to use, both as a back-end library
      to build XNAT clients and as an alternative front-end from the command line.

PMID- 22654753
TI  - EEGVIS: A MATLAB Toolbox for Browsing, Exploring, and Viewing Large Datasets.
AB  - Recent advances in data monitoring and sensor technology have accelerated the
      acquisition of very large data sets. Streaming data sets from instrumentation
      such as multi-channel EEG recording usually must undergo substantial pre
      processing and artifact removal. Even when using automated procedures, most
      scientists engage in laborious manual examination and processing to assure high
      quality data and to indentify interesting or problematic data segments.
      Researchers also do not have a convenient method of method of visually assessing
      the effects of applying any stage in a processing pipeline. EEGVIS is a MATLAB
      toolbox that allows users to quickly explore multi-channel EEG and other large
      array-based data sets using multi-scale drill-down techniques. Customizable
      summary views reveal potentially interesting sections of data, which users can
      explore further by clicking to examine using detailed viewing components. The
      viewer and a companion browser are built on our MoBBED framework, which has a
      library of modular viewing components that can be mixed and matched to best
      reveal structure. Users can easily create new viewers for their specific data
      without any programming during the exploration process. These viewers
      automatically support pan, zoom, resizing of individual components, and cursor
      exploration. The toolbox can be used directly in MATLAB at any stage in a
      processing pipeline, as a plug-in for EEGLAB, or as a standalone precompiled
      application without MATLAB running. EEGVIS and its supporting packages are freely
      available under the GNU general public license at
      http://visual.cs.utsa.edu/eegvis.

PMID- 22654754
TI  - Image quality analysis of high-density diffuse optical tomography incorporating a
      subject-specific head model.
AB  - High-density diffuse optical tomography (HD-DOT) methods have shown significant
      improvement in localization accuracy and image resolution compared to traditional
      topographic near infrared spectroscopy of the human brain. In this work we
      provide a comprehensive evaluation of image quality in visual cortex mapping via
      a simulation study with the use of an anatomical head model derived from MRI data
      of a human subject. A model of individual head anatomy provides the surface shape
      and internal structure that allow for the construction of a more realistic
      physical model for the forward problem, as well as the use of a structural
      constraint in the inverse problem. The HD-DOT model utilized here incorporates
      multiple source-detector separations with continuous-wave data with added noise
      based on experimental results. To evaluate image quality we quantify the
      localization error and localized volume at half maximum (LVHM) throughout a
      region of interest within the visual cortex and systematically analyze the use of
      whole-brain tissue spatial constraint within image reconstruction. Our results
      demonstrate that an image quality with less than 10 mm in localization error and
      1000 m(3) in LVHM can be obtained up to 13 mm below the scalp surface with a
      typical unconstrained reconstruction and up to 18 mm deep when a whole-brain
      spatial constraint based on the brain tissue is utilized.

PMID- 22654749
TI  - The role of prediction in social neuroscience.
AB  - Research has shown that the brain is constantly making predictions about future
      events. Theories of prediction in perception, action and learning suggest that
      the brain serves to reduce the discrepancies between expectation and actual
      experience, i.e., by reducing the prediction error. Forward models of action and
      perception propose the generation of a predictive internal representation of the
      expected sensory outcome, which is matched to the actual sensory feedback. Shared
      neural representations have been found when experiencing one's own and observing
      other's actions, rewards, errors, and emotions such as fear and pain. These
      general principles of the "predictive brain" are well established and have
      already begun to be applied to social aspects of cognition. The application and
      relevance of these predictive principles to social cognition are discussed in
      this article. Evidence is presented to argue that simple non-social cognitive
      processes can be extended to explain complex cognitive processes required for
      social interaction, with common neural activity seen for both social and non
      social cognitions. A number of studies are included which demonstrate that bottom
      up sensory input and top-down expectancies can be modulated by social
      information. The concept of competing social forward models and a partially
      distinct category of social prediction errors are introduced. The evolutionary
      implications of a "social predictive brain" are also mentioned, along with the
      implications on psychopathology. The review presents a number of testable
      hypotheses and novel comparisons that aim to stimulate further discussion and
      integration between currently disparate fields of research, with regard to
      computational models, behavioral and neurophysiological data. This promotes a
      relatively new platform for inquiry in social neuroscience with implications in
      social learning, theory of mind, empathy, the evolution of the social brain, and
      potential strategies for treating social cognitive deficits.

PMID- 22654755
TI  - Current understanding of the glial response to disorders of the aging CNS.
AB  - In this special issue of Frontiers in Pharmacology, we have asked leading experts
      to comment and review the evidence that inflammatory cells play a leading role in
      the pathological processes underlying neurodegenerative disorders. We now seek to
      draw these various observations together into a conclusion, with the hope that
      this will inform further work in this area and result in the identification of
      new therapeutic targets that will have a disease modifying effect.

PMID- 22654756
TI  - Molecular dynamics simulations of voltage-gated cation channels: insights on
      voltage-sensor domain function and modulation.
AB  - Since their discovery in the 1950s, the structure and function of voltage-gated
      cation channels (VGCC) has been largely understood thanks to results stemming
      from electrophysiology, pharmacology, spectroscopy, and structural biology. Over
      the past decade, computational methods such as molecular dynamics (MD)
      simulations have also contributed, providing molecular level information that can
      be tested against experimental results, thereby allowing the validation of the
      models and protocols. Importantly, MD can shed light on elements of VGCC function
      that cannot be easily accessed through "classical" experiments. Here, we review
      the results of recent MD simulations addressing key questions that pertain to the
      function and modulation of the VGCC's voltage-sensor domain (VSD) highlighting:
      (1) the movement of the S4-helix basic residues during channel activation,
      articulating how the electrical driving force acts upon them; (2) the nature of
      the VSD intermediate states on transitioning between open and closed states of
      the VGCC; and (3) the molecular level effects on the VSD arising from mutations
      of specific S4 positively charged residues involved in certain genetic diseases.

PMID- 22654757
TI  - The Prostaglandin F Synthase Activity of the Human Aldose Reductase AKR1B1 Brings
      New Lenses to Look at Pathologic Conditions.
AB  - Prostaglandins are important regulators of female reproductive functions to which
      aldose reductases exhibiting hydroxysteroid dehydrogenase activity also
      contribute. Our work on the regulation of reproductive function by prostaglandins
      (PGs), lead us to the discovery that AKR1B5 and later AKR1B1were highly efficient
      and physiologically relevant PGF synthases. PGE2 and PGF2alpha are the main
      prostanoids produced in the human endometrium and proper balance in their
      relative production is important for normal menstruation and optimal fertility.
      Recent evidence suggests that PGE2/EP2 and PGF2alpha/FP may constitute a
      functional dyad with physiological relevance comparable to the prostacyclin
      thromboxane dyad in the vascular system. We have recently reported that AKR1B1
      was expressed and modulated in association with PGF2alpha production in response
      to IL-1beta in the human endometrium. In the present study, we show that the
      human AKR1B1 (gene ID: 231) also known as ALDR1 or ALR2 is a functional PGF2alpha
      synthase in different models of living cells and tissues. Using human endometrial
      cells, prostate, and vascular smooth muscle cells, cardiomyocytes and endothelial
      cells we demonstrate that IL-1beta is able to up regulate COX-2 and AKR1B1
      proteins as well as PGF2alpha production under normal glucose concentrations. We
      show that the promoter activity of AKR1B1 gene is increased by IL-1beta
      particularly around the multiple stress response region containing two putative
      antioxidant response elements adjacent to TonE and AP1. We also show that AKR1B1
      is able to regulate PGE2 production through PGF2alpha acting on its FP receptor
      and that aldose reductase inhibitors like alrestatin, Statil (ponalrestat), and
      EBPC exhibit distinct and characteristic inhibition of PGF2alpha production in
      different cell models. The PGF synthase activity of AKR1B1 represents a new and
      important target to regulate ischemic and inflammatory responses associated with
      several human pathologies.

PMID- 22654758
TI  - Voltage sensor inactivation in potassium channels.
AB  - In voltage-gated potassium (Kv) channels membrane depolarization causes movement
      of a voltage sensor domain. This conformational change of the protein is
      transmitted to the pore domain and eventually leads to pore opening. However, the
      voltage sensor domain may interact with two distinct gates in the pore domain:
      the activation gate (A-gate), involving the cytoplasmic S6 bundle crossing, and
      the pore gate (P-gate), located externally in the selectivity filter. How the
      voltage sensor moves and how tightly it interacts with these two gates on its way
      to adopt a relaxed conformation when the membrane is depolarized may critically
      determine the mode of Kv channel inactivation. In certain Kv channels, voltage
      sensor movement leads to a tight interaction with the P-gate, which may cause
      conformational changes that render the selectivity filter non-conductive ("P/C
      type inactivation"). Other Kv channels may preferably undergo inactivation from
      pre-open closed-states during voltage sensor movement, because the voltage sensor
      temporarily uncouples from the A-gate. For this behavior, known as "preferential"
      closed-state inactivation, we introduce the term "A/C-type inactivation".
      Mechanistically, P/C- and A/C-type inactivation represent two forms of "voltage
      sensor inactivation."

PMID- 22654759
TI  - Association of Cannabis Use during Adolescence, Prefrontal CB1 Receptor
      Signaling, and Schizophrenia.
AB  - The cannabinoid receptor 1 (CB1R) is the G-protein coupled receptor responsible
      for the majority of the endocannabinoid signaling in the human brain. It is
      widely distributed in the limbic system, basal ganglia, and cerebellum, which are
      areas responsible for cognition, memory, and motor control. Because of this
      widespread distribution, it is not surprising that drugs that activate CB1R have
      expected behavioral outcomes consistent with dysregulated signaling from these
      areas (e.g., memory loss, cognitive deficits, etc). In the context of this
      review, we present evidence for the role of CB1R signaling in the prefrontal
      cortex (PFC), an area involved in executive functions, with emphasis on the
      developmental regulation of CB1R signaling in the acquisition of mature PFC
      function. We further hypothesize how alterations in CB1R signaling specifically
      during adolescent maturation might confer liability to psychiatric disorders.

PMID- 22654760
TI  - A trade-off study revealing nested timescales of constraint.
AB  - This study investigates human performance in a cyclic Fitts task at three
      different scales of observation, either in the presence (difficult condition) or
      in the absence (easy condition) of a speed-accuracy trade-off. At the fastest
      scale, the harmonicity of the back and forth movements, which reflects the
      dissipation of mechanical energy, was measured within the timeframe of single
      trials. At an intermediate scale, speed and accuracy measures were determined
      over a trial. The slowest scale pertains to the temporal structure of movement
      variability, which evolves over multiple trials. In the difficult condition,
      reliable correlations across each of the measures corroborated a coupling of
      nested scales of performance. Participants who predominantly emphasized the speed
      side of the trade-off (despite the instruction to be both fast and accurate)
      produced more harmonic movements and clearer 1/f scaling in the produced movement
      time series, but were less accurate and produced more random variability in the
      produced movement amplitudes (vice versa for more accurate participants). This
      implied that speed-accuracy trade-off was accompanied by a trade-off between
      temporal and spatial streams of 1/f scaling, as confirmed by entropy measures. In
      the easy condition, however, no trade-offs nor couplings among scales of
      performance were observed. Together, these results suggest that 1/f scaling is
      more than just a byproduct of cognition. These findings rather support the claim
      that interaction-dominant dynamics constitute a coordinative basis for goal
      directed behavior.

PMID- 22654761
TI  - Diagnostic dilemmas: overlapping features of brugada syndrome and arrhythmogenic
      right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) and Brugada syndrome are
      distinct clinical entities which diagnostic criteria exclude their coexistence in
      individual patients. ARVC is a myocardial disorder characterized by fibro-fatty
      replacement of the myocardium and ventricular arrhythmias. In contrast, the
      Brugada syndrome has long been considered a functional cardiac disorder: no gross
      structural abnormalities can be identified in the majority of patients and its
      electrocardiographic hallmark of coved-type ST-segment elevation in right
      precordial leads is dynamic. Nonetheless, a remarkable overlap in clinical
      features has been demonstrated between these conditions. This review focuses on
      this overlap and discusses its potential causes and consequences.

PMID- 22654762
TI  - Emerging role of neuronal exosomes in the central nervous system.
AB  - Exosomes are small extracellular vesicles, which stem from endosomes fusing with
      the plasma membrane, and can be recaptured by receiving cells. They contain
      lipids, proteins, and RNAs able to modify the physiology of receiving cells.
      Functioning of the brain relies on intercellular communication between neural
      cells. These communications can modulate the strength of responses at sparse
      groups of specific synapses, to modulate circuits underlying associations and
      memory. Expression of new genes must then follow to stabilize the long-term
      modifications of the synaptic response. Local changes of the physiology of
      synapses from one neuron driven by another, have so far been explained by
      classical signal transduction to modulate transcription, translation, and
      posttranslational modifications. In vitro evidence now demonstrates that exosomes
      are released by neurons in a way depending on synaptic activity; these exosomes
      can be retaken by other neurons suggesting a novel way for inter-neuronal
      communication. The efficacy of inter-neuronal transfer of biochemical information
      allowed by exosomes would be far superior to that of direct cell-to-cell contacts
      or secreted soluble factors. Indeed, lipids, proteins, and RNAs contained in
      exosomes secreted by emitting neurons could directly modify signal transduction
      and protein expression in receiving cells. Exosomes could thus represent an ideal
      mechanism for inter-neuronal transfer of information allowing anterograde and
      retrograde signaling across synapses necessary for plasticity. They might also
      allow spreading across the nervous system of pathological proteins like PrPsc,
      APP fragments, phosphorylated Tau, or Alpha-synuclein.

PMID- 22654763
TI  - Amplitude Changes during Ventricular Fibrillation: A Mechanistic Insight.
AB  - INTRODUCTION: Clinically in ventricular fibrillation (VF), ECG amplitude, and
      frequency decrease as ischemia progresses and predict defibrillation success. In
      vitro ECG amplitude declines without ischemia, independent of VF frequencies.
      This study examines the contribution of cellular electrical activity and global
      organization to ECG amplitude changes during VF. METHODS AND RESULTS: Rabbit
      hearts were Langendorff-perfused (40 mL/min, Tyrode's solution) and loaded with
      RH237. During VF, ECG, and epicardial optical action potentials were recorded
      (photodiode array; 256 sites, 15 mm * 15 mm). After 60 s of VF, perfusion was
      either maintained, global ischemia produced by low-flow (6 mL/min), or solution
      [K(+)](o) raised to 8 mM. Peak-to-peak amplitude was determined for all signals.
      During VF, in control, ECG amplitude decreased to a steady-state (~57% baseline),
      whereas in low-flow steady-state was not reached with the amplitude continuing to
      fall to 33% of baseline by 600 s. Optically, LV amplitude declined more than RV,
      reaching significance in control (LV vs. RV; 33 +/- 5 vs. 63 +/- 8%, p < 0.01).
      During VF in 8 mM [K(+)](o), amplitude changes were more complex; ECG amplitude
      increased with time (105 +/- 13%), whilst LV amplitude decreased (60 +/- 15%, p <
      0.001). Microelectrode studies showed amplitude reduction in control and 8 mM
      [K(+)](o) (to ~79 and ~93% baseline, respectively). Evaluation of electrical
      coordination by cross-correlation of optical signals showed as VF progressed
      coordination reduced in control (baseline 0.36 +/- 0.02 to 0.28 +/- 0.003, p <
      0.01), maintained in low-flow (0.41 +/- 0.03 to 0.37 +/- 0.005, p = NS) and
      increased in 8 mM [K(+)](o) (0.36 +/- 0.02 to 0.53 +/- 0.08, p < 0.05).
      CONCLUSION: ECG amplitude decline in VF is due to a combination of decreased
      systolic activation at the cellular level and increased desynchronization of
      inter-cellular electrical activity.

PMID- 22654764
TI  - Role of editing of R-R intervals in the analysis of heart rate variability.
AB  - This paper reviews the methods used for editing of the R-R interval time series
      and how this editing can influence the results of heart rate (HR) variability
      analyses. Measurement of HR variability from short and long-term
      electrocardiographic (ECG) recordings is a non-invasive method for evaluating
      cardiac autonomic regulation. HR variability provides information about the
      sympathetic-parasympathetic autonomic balance. One important clinical application
      is the measurement of HR variability in patients suffering from acute myocardial
      infarction. However, HR variability signals extracted from R-R interval time
      series from ambulatory ECG recordings often contain different amounts of
      artifact. These false beats can be either of physiological or technical origin.
      For instance, technical artifact may result from poorly fastened electrodes or be
      due to motion of the subject. Ectopic beats and atrial fibrillation are examples
      of physiological artifact. Since ectopic and other false beats are common in the
      R-R interval time series, they complicate the reliable analysis of HR variability
      sometimes making it impossible. In conjunction with the increased usage of HR
      variability analyses, several studies have confirmed the need for different
      approaches for handling false beats present in the R-R interval time series. The
      editing process for the R-R interval time series has become an integral part of
      these analyses. However, the published literature does not contain detailed
      reviews of editing methods and their impact on HR variability analyses. Several
      different editing and HR variability signal pre-processing methods have been
      introduced and tested for the artifact correction. There are several approaches
      available, i.e., use of methods involving deletion, interpolation or filtering
      systems. However, these editing methods can have different effects on HR
      variability measures. The effects of editing are dependent on the study setting,
      editing method, parameters used to assess HR variability, type of study
      population, and the length of R-R interval time series. The purpose of this paper
      is to summarize these pre-processing methods for HR variability signal, focusing
      especially on the editing of the R-R interval time series.

PMID- 22654765
TI  - Xanthine oxidase and uric Acid in atrial fibrillation.

PMID- 22654766
TI  - Fish, Marine n-3 Fatty Acids, and Atrial Fibrillation - Experimental Data and
      Clinical Effects.
AB  - Marine n-3 polyunsaturated fatty acids (PUFA) may have beneficial effects in
      relation to atrial fibrillation (AF) with promising data from experimental animal
      studies, however, results from studies in humans have been inconsistent. This
      review evaluates the mechanisms of action of marine n-3 PUFA in relation to AF
      based on experimental data and provides a status on the evidence obtained from
      observational studies and interventional trials. In conclusion, there is growing
      evidence for an effect of marine n-3 PUFA in prevention and treatment of AF.
      However, further studies are needed to establish which patients are more likely
      to benefit from n-3 PUFA, the timing of treatment, and dosages.

PMID- 22654767
TI  - Firing patterns of muscle vasoconstrictor neurons in respiratory disease.
AB  - Because the cardiovascular system and respiration are so intimately coupled,
      disturbances in respiratory control often lead to disturbances in cardiovascular
      control. Obstructive Sleep Apnea (OSA), Chronic Obstructive Pulmonary Disease
      (COPD), and Bronchiectasis (BE) are all associated with a greatly elevated muscle
      vasoconstrictor drive (muscle sympathetic nerve activity, MSNA). Indeed, the
      increase in MSNA is comparable to that seen in congestive heart failure (CHF), in
      which the increase in MSNA compensates for the reduced cardiac output and thereby
      assists in maintaining blood pressure. However, in OSA - but not COPD or BE - the
      increase in MSNA can lead to hypertension. Here, the features of the
      sympathoexcitation in OSA, COPD, and BE are reviewed in terms of the firing
      properties of post-ganglionic muscle vasoconstrictor neurons. Compared to healthy
      subjects with low levels of resting MSNA, single-unit recordings revealed that
      the augmented MSNA seen in OSA, BE, COPD, and CHF were each associated with an
      increase in firing probability and mean firing rates of individual neurons.
      However, unlike patients with heart failure, all patients with respiratory
      disease exhibited an increase in multiple within-burst firing which, it is
      argued, reflects an increase in central sympathetic drive. Similar patterns to
      those seen in OSA, COPD, and BE were seen in healthy subjects during an acute
      increase in muscle vasoconstrictor drive. These observations emphasize the
      differences by which the sympathetic nervous system grades its output in health
      and disease, with an increase in firing probability of active neurons and
      recruitment of additional neurons being the dominant mechanisms.

PMID- 22654769
TI  - Phenotyping cowpeas for adaptation to drought.
AB  - Methods for phenotyping cowpeas for adaptation to drought are reviewed. Key
      factors involve achieving optimal time of flowering and cycle length, and
      appropriate morphology for different types of cultivars as they relate to their
      utilization for dry grain, hay, and fresh pea production. Strong resistance to
      vegetative-stage drought is available and should be incorporated. The extreme
      ability of extra-early erect cowpea cultivars to escape terminal drought should
      be exploited in zones with very short rainfall seasons. In zones with the
      possibility of limited rainfall in the middle of the growing season, resistance
      to mid-season drought, and the delayed-leaf-senescence trait can be valuable.
      Breeding for water-use efficiency, deeper rooting, and heat tolerance are
      discussed. Diseases and pests that influence adaptation to drought are
      considered. Resistance to the organism causing ashy stem blight disease should be
      incorporated because this disease can destroy cowpea seedlings under hot, dry
      soil conditions. The value of varietal intercrops with contrasting types of
      cowpea cultivars in enhancing adaptation to drought is described. Implications of
      cowpea/cereal rotations for cowpea breeding are discussed. Breeding strategies
      for enhancing cowpea adaptation to drought are described.

PMID- 22654768
TI  - Role of betaPix in the Kidney.
AB  - Small GTPases function as molecular switches in cell signaling, alternating
      between an inactive, GDP-bound state, and active GTP-bound state. betaPix is one
      of guanine nucleotide exchange factors (GEFs) that catalyze the exchange of bound
      GDP for ambient GTP. The central goal of this review article is to summarize
      recent findings on betaPix and the role it plays in kidney pathology and
      physiology. Recent studies shed new light on several key questions concerning the
      signaling mechanisms mediated by betaPix. This manuscript provides a review of
      the various mechanisms whereby betaPix has been shown to function within the
      kidney through a wide range of actions. Both canonical GEF activity and non
      canonical signaling pathways mediated by betaPix are discussed. Distribution
      patterns of betaPix in the kidney will be also covered. Much has yet to be
      discerned, but it is clear that betaPix plays a significant role in the kidney.

PMID- 22654770
TI  - Extrasynaptic release of serotonin affects the social dynamics of leeches.

PMID- 22654771
TI  - Inhibitory Processes for Critical Situations - The Role of n-2 Task Repetition
      Costs in Human Multitasking Situations.
AB  - The human cognitive system is equipped with various processes for dealing with
      everyday challenges. One of such processes is the inhibition of currently
      irrelevant goals or mental task-sets, which can be seen as a response to the
      critical event of information overflow in the cognitive system and challenging
      the cognitive system's ability to keep track of ongoing demands. In two
      experiments, we investigate the flexibility of the inhibitory process by
      inserting rare non-critical events (25% of all trials), operationalized as
      univalent stimuli (i.e., unambiguous stimuli that call for only one specific task
      in a multitasking context), and by introducing the possibility to prepare for an
      upcoming task (Experiment 2). We found that the inhibitory process is not
      influenced by a cue informing subjects about the upcoming occurrence of a
      univalent stimulus. However, the introduction of univalent stimuli allowed
      preparatory processes to modify the impact of the inhibitory process. Therefore,
      our results suggest that inhibitory processes are engaged in a rather global
      manner, not taking into account variations in stimulus valence, which we took as
      operationalization of critical, conflict-inducing events in the ongoing stream of
      information processing. However, rare uncritical events, such as univalent
      stimuli that do not cause conflict and interference in the processing stream,
      appear to alter the way the cognitive system can take advantage of preparatory
      processes.

PMID- 22654772
TI  - Glutathione supplementation attenuates lipopolysaccharide-induced mitochondrial
      dysfunction and apoptosis in a mouse model of acute lung injury.
AB  - Acute lung injury (ALI) is a life threatening condition associated with
      hypoxemia, diffuse alveolar damage, inflammation, and loss of lung function.
      Lipopolysaccharide (LPS; endotoxin) from the outer membrane of Gram-negative
      bacteria is a major virulence factor involved in the development of ALI. The
      depletion of glutathione (GSH), an essential intra- and extra-cellular protective
      antioxidant, by LPS is an important event that contributes to the elevation in
      reactive oxygen species. Whether restoring GSH homeostasis can effectively
      ameliorate mitochondrial dysfunction and cellular apoptosis in ALI is unknown and
      therefore, was the focus of this study. In peripheral lung tissue of LPS-treated
      mice, hydrogen peroxide and protein nitration levels were significantly
      increased. Pre-treatment with GSH-ethyl ester (GSH-EE) prevented this increase in
      oxidative stress. LPS also increased the lactate/pyruvate ratio, attenuated SOD2
      protein levels, and decreased ATP levels in the mouse lung indicative of
      mitochondrial dysfunction. Again, GSH-EE treatment preserved the mitochondrial
      function. Finally, our studies showed that LPS induced an increase in the
      mitochondrial translocation of Bax, caspase 3 activation, and nuclear DNA
      fragmentation and these parameters were all prevented with GSH-EE. Thus, this
      study suggests that GSH-EE supplementation may reduce the mitochondrial
      dysfunction associated with ALI.

PMID- 22654773
TI  - Modulation of ionotropic glutamate receptors and Acid-sensing ion channels by
      nitric oxide.
AB  - Ionotropic glutamate receptors (iGluR) are ligand-gated ion channels and are
      densely expressed in broad areas of mammalian brains. Like iGluRs, acid-sensing
      ion channels (ASIC) are ligand (H(+))-gated channels and are enriched in brain
      cells and peripheral sensory neurons. Both ion channels are enriched at
      excitatory synaptic sites, functionally coupled to each other, and subject to the
      modulation by a variety of signaling molecules. Central among them is a
      gasotransmitter, nitric oxide (NO). Available data show that NO activity
      dependently modulates iGluRs and ASICs via either a direct or an indirect
      pathway. The former involves a NO-based and cGMP-independent post-translational
      modification (S-nitrosylation) of extracellular cysteine residues in channel
      subunits or channel-interacting proteins. The latter is achieved by NO activation
      of soluble guanylyl cyclase, which in turn triggers an intracellular cGMP
      sensitive cascade to indirectly modulate iGluRs and ASICs. The NO modification is
      usually dynamic and reversible. Modified channels undergo significant,
      interrelated changes in biochemistry and electrophysiology. Since NO synthesis is
      enhanced in various neurological disorders, the NO modulation of iGluRs and ASICs
      is believed to be directly linked to the pathogenesis of these disorders. This
      review summarizes the direct and indirect modifications of iGluRs and ASICs by NO
      and analyzes the role of the NO-iGluR and NO-ASIC coupling in cell signaling and
      in the pathogenesis of certain related neurological diseases.

PMID- 22654775
TI  - From gr8 to great: Lexical Access to SMS Shortcuts.
AB  - Many contemporary texts include shortcuts, such as cu or phones4u. The aim of
      this study was to investigate how the meanings of shortcuts are retrieved. A
      primed lexical decision paradigm was used with shortcuts and the corresponding
      words as primes. The target word was associatively related to the meaning of the
      whole prime (cu/see you - goodbye), to a component of the prime (cu/see you -
      look), or unrelated to the prime. In Experiment 1, primes were presented for 57
      ms. For both word and shortcut primes, responses were faster to targets preceded
      by whole-related than by unrelated primes. No priming from component-related
      primes was found. In Experiment 2, the prime duration was 1000 ms. The priming
      effect seen in Experiment 1 was replicated. Additionally, there was priming from
      component-related word primes, but not from component-related shortcut primes.
      These results indicate that the meanings of shortcuts can be retrieved without
      translating them first into corresponding words.

PMID- 22654774
TI  - Increased Orbitofrontal Brain Activation after Administration of a Selective
      Adenosine A(2A) Antagonist in Cocaine Dependent Subjects.
AB  - BACKGROUND: Positron Emission Tomography imaging studies provide evidence of
      reduced dopamine function in cocaine dependent subjects in the striatum, which is
      correlated with prefrontal cortical glucose metabolism, particularly in the
      orbitofrontal cortex. However, whether enhancement of dopamine in the striatum in
      cocaine dependent subjects would be associated with changes in prefrontal
      cortical brain activation is unknown. One novel class of medications that enhance
      dopamine function via heteromer formation with dopamine receptors in the striatum
      is the selective adenosine A(2A) receptor antagonists. This study sought to
      determine the effects administration of the selective adenosine A(2A) receptor
      antagonist SYN115 on brain function in cocaine dependent subjects.
      METHODOLOGY/PRINCIPLE FINDINGS: Twelve cocaine dependent subjects underwent two
      fMRI scans (one after a dose of placebo and one after a dose of 100 mg of SYN115)
      while performing a working memory task with three levels of difficulty (3, 5, and
      7 digits). fMRI results showed that for 7-digit working memory activation there
      was significantly greater activation from SYN115 compared to placebo in portions
      of left (L) lateral orbitofrontal cortex, L insula, and L superior and middle
      temporal pole. CONCLUSION/SIGNIFICANCE: These findings are consistent with
      enhanced dopamine function in the striatum in cocaine dependent subjects via
      blockade of adenosine A(2A) receptors producing increased brain activation in the
      orbitofrontal cortex and other cortical regions. This suggests that at least some
      of the changes in brain activation in prefrontal cortical regions in cocaine
      dependent subjects may be related to altered striatal dopamine function, and that
      enhancement of dopamine function via adenosine A(2A) receptor blockade could be
      explored further for amelioration of neurobehavioral deficits associated with
      chronic cocaine use.

PMID- 22654776
TI  - Perceptions as hypotheses: saccades as experiments.
AB  - If perception corresponds to hypothesis testing (Gregory, 1980); then visual
      searches might be construed as experiments that generate sensory data. In this
      work, we explore the idea that saccadic eye movements are optimal experiments, in
      which data are gathered to test hypotheses or beliefs about how those data are
      caused. This provides a plausible model of visual search that can be motivated
      from the basic principles of self-organized behavior: namely, the imperative to
      minimize the entropy of hidden states of the world and their sensory
      consequences. This imperative is met if agents sample hidden states of the world
      efficiently. This efficient sampling of salient information can be derived in a
      fairly straightforward way, using approximate Bayesian inference and variational
      free-energy minimization. Simulations of the resulting active inference scheme
      reproduce sequential eye movements that are reminiscent of empirically observed
      saccades and provide some counterintuitive insights into the way that sensory
      evidence is accumulated or assimilated into beliefs about the world.

PMID- 22654777
TI  - Bilingual and monolingual children attend to different cues when learning new
      words.
AB  - The way in which children learn language can vary depending on their language
      environment. Previous work suggests that bilingual children may be more sensitive
      to pragmatic cues from a speaker when learning new words than monolingual
      children are. On the other hand, monolingual children may rely more heavily on
      object properties than bilingual children do. In this study we manipulate these
      two sources of information within the same paradigm, using eye gaze as a
      pragmatic cue and similarity along different dimensions as an object cue. In the
      crucial condition, object and pragmatic cues were inconsistent with each other.
      Our results showed that in this ambiguous condition monolingual children attend
      more to object property cues whereas bilingual children attend more to pragmatic
      cues. Control conditions showed that monolingual children were sensitive to eye
      gaze and bilingual children were sensitive to similarity by shape; it was only
      when the cues were inconsistent that children's preference for one or the other
      cue was apparent. Our results suggest that children learn to weigh different cues
      depending on their relative informativeness in their environment.

PMID- 22654778
TI  - Processing of audiovisual associations in the human brain: dependency on
      expectations and rule complexity.
AB  - In order to respond to environmental changes appropriately, the human brain must
      not only be able to detect environmental changes but also to form expectations of
      forthcoming events. The events in the external environment often have a number of
      multisensory features such as pitch and form. For integrated percepts of objects
      and events, crossmodal processing, and crossmodally induced expectations of
      forthcoming events are needed. The aim of the present study was to determine
      whether the expectations created by visual stimuli can modulate the deviance
      detection in the auditory modality, as reflected by auditory event-related
      potentials (ERPs). Additionally, it was studied whether the complexity of the
      rules linking auditory and visual stimuli together affects this process. The N2
      deflection of the ERP was observed in response to violations in the subjects'
      expectation of a forthcoming tone. Both temporal aspects and cognitive demands
      during the audiovisual deviance detection task modulated the brain processes
      involved.

PMID- 22654780
TI  - Attentional capture by irrelevant transients leads to perceptual errors in a
      competitive change detection task.
AB  - Theories on visual change detection imply that attention is a necessary but not
      sufficient prerequisite for aware perception. Misguidance of attention due to
      salient irrelevant distractors can therefore lead to severe deficits in change
      detection. The present study investigates the mechanisms behind such perceptual
      errors and their relation to error processing on higher cognitive levels.
      Participants had to detect a luminance change that occasionally occurred
      simultaneously with an irrelevant orientation change in the opposite hemi-field
      (conflict condition). By analyzing event-related potentials in the EEG separately
      in those error prone conflict trials for correct and erroneous change detection,
      we demonstrate that only correct change detection was associated with the
      allocation of attention to the relevant luminance change. Erroneous change
      detection was associated with an initial capture of attention toward the
      irrelevant orientation change in the N1 time window and a lack of subsequent
      target selection processes (N2pc). Errors were additionally accompanied by an
      increase of the fronto-central N2 and a kind of error negativity (Ne or ERN),
      which, however, peaked prior to the response. These results suggest that a strong
      perceptual conflict by salient distractors can disrupt the further processing of
      relevant information and thus affect its aware perception. Yet, it does not
      impair higher cognitive processes for conflict and error detection, indicating
      that these processes are independent from awareness.

PMID- 22654781
TI  - Food, "culture," and sociality in Drosophila.

PMID- 22654779
TI  - Early and sustained supramarginal gyrus contributions to phonological processing.
AB  - Reading is a difficult task that, at a minimum, requires recognizing a visual
      stimulus and linking it with its corresponding sound and meaning. Neurologically,
      this involves an anatomically distributed set of brain regions cooperating to
      solve the problem. It has been hypothesized that the supramarginal gyrus (SMG)
      contributes preferentially to phonological aspects of word processing and thus
      plays an important role in visual word recognition. Here, we used chronometric
      transcranial magnetic stimulation (TMS) to investigate the functional specificity
      and timing of SMG involvement in reading visually presented words. Participants
      performed tasks designed to focus on either the phonological, semantic, or visual
      aspects of written words while double pulses of TMS (delivered 40 ms apart) were
      used to temporarily interfere with neural information processing in the left SMG
      at five different time windows. Stimulation at 80/120, 120/160, and 160/200 ms
      post-stimulus onset significantly slowed subjects' reaction times in the
      phonological task. This inhibitory effect was specific to the phonological
      condition, with no effect of TMS in the semantic or visual tasks, consistent with
      claims that SMG contributes preferentially to phonological aspects of word
      processing. The fact that the effect began within 80-120 ms of the onset of the
      stimulus and continued for approximately 100 ms, indicates that phonological
      processing initiates early and is sustained over time. These findings are
      consistent with accounts of visual word recognition that posit parallel
      activation of orthographic, phonological, and semantic information that interact
      over time to settle into a distributed, but stable, representation of a word.

PMID- 22654783
TI  - Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis.
AB  - Resveratrol is a naturally occurring polyphenol that activates SIRT1, an NAD
      dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with
      enhanced systemic absorption, prevents neuronal loss without suppressing
      inflammation in mice with relapsing experimental autoimmune encephalomyelitis
      (EAE), a model of multiple sclerosis (MS). In contrast, resveratrol has been
      reported to suppress inflammation in chronic EAE, although neuroprotective
      effects were not evaluated. The current studies examine potential neuroprotective
      and immunomodulatory effects of resveratrol in chronic EAE induced by
      immunization with myelin oligodendroglial glycoprotein peptide in C57/Bl6 mice.
      Effects of two distinct formulations of resveratrol administered daily orally
      were compared. Resveratrol delayed the onset of EAE compared to vehicle-treated
      EAE mice, but did not prevent or alter the phenotype of inflammation in spinal
      cords or optic nerves. Significant neuroprotective effects were observed, with
      higher numbers of retinal ganglion cells found in eyes of resveratrol-treated EAE
      mice with optic nerve inflammation. Results demonstrate that resveratrol prevents
      neuronal loss in this chronic demyelinating disease model, similar to its effects
      in relapsing EAE. Differences in immunosuppression compared with prior studies
      suggest that immunomodulatory effects may be limited and may depend on specific
      immunization parameters or timing of treatment. Importantly, neuroprotective
      effects can occur without immunosuppression, suggesting a potential additive
      benefit of resveratrol in combination with anti-inflammatory therapies for MS.

PMID- 22654782
TI  - Cognitive dysfunction in multiple sclerosis.
AB  - In Multiple Sclerosis (MS) prevalence studies of community and clinical samples,
      indicate that 45-60% of patients are cognitively impaired. These cognitive
      dysfunctions have been traditionally described as heterogeneous, but more recent
      studies suggest that there is a specific pattern of MS-related cognitive
      dysfunctions. With the advent of disease-modifying medications for MS and
      emphasis on early intervention and treatment, detection of cognitive impairment
      at its earliest stage becomes particularly important. In this review the authors
      address: the cognitive domains most commonly impaired in MS (memory, attention,
      executive functions, speed of information processing, and visual-spatial
      abilities); the pathophysiological mechanism implied in MS cognitive dysfunction
      and correlated brain MRI features; the importance of neuropsychological
      assessment of MS patients in different stages of the disease and the influence of
      its course on cognitive performance; the most used tests and batteries for
      neuropsychological assessment; therapeutic strategies to improve cognitive
      abilities.

PMID- 22654784
TI  - Intracerebral hemorrhage: toward physiological imaging of hemorrhage risk in
      acute and chronic bleeding.
AB  - Despite improvements in management and prevention of intracerebral hemorrhage
      (ICH), there has been little improvement in mortality over the last 30 years.
      Hematoma expansion, primarily during the first few hours is highly predictive of
      neurological deterioration, poor functional outcome, and mortality. For each 10%
      increase in ICH size, there is a 5% increase in mortality and an additional 16%
      chance of poorer functional outcome. As such, both the identification and
      prevention of hematoma expansion are attractive therapeutic targets in ICH.
      Previous studies suggest that contrast extravasation seen on CT Angiography
      (CTA), MRI, and digital subtraction angiography correlates with hematoma growth,
      indicating ongoing bleeding. Contrast extravasation on the arterial phase of a
      CTA has been coined the CTA Spot Sign. These easily identifiable foci of contrast
      enhancement have been identified as independent predictors of hematoma growth,
      mortality, and clinical outcome in primary ICH. The Spot Sign score, developed to
      stratify risk of hematoma expansion, has shown high inter-observer agreement.
      Post-contrast leakage or delayed CTA Spot Sign, on post contrast CT following CTA
      or delayed CTA respectively are seen in an additional ~8% of patients and explain
      apparently false negative observations on early CTA imaging in patients
      subsequently undergoing hematoma expansion. CT perfusion provides an opportunity
      to acquire dynamic imaging and has been shown to quantify rates of contrast
      extravasation. Intravenous recombinant factor VIIa (rFVIIa) within 4 h of ICH
      onset has been shown to significantly reduce hematoma growth. However, clinical
      efficacy has yet to be proven. There is compelling evidence that cerebral amyloid
      angiopathy (CAA) may precede the radiographic evidence of vascular disease and as
      such contribute to microbleeding. The interplay between microbleeding, CAA, CTA
      Spot Sign and genetic composition (ApoE genotype) may be crucial in developing a
      risk model for ICH.

PMID- 22654786
TI  - Challenges for Cellular Endocrinology: Improving the Detection Methods and
      Closing the Gap between in Vitro and in Vivo Observations.

PMID- 22654787
TI  - Circulating TNF-Alpha and IL-6 Concentrations and TNF-Alpha -308 G > A
      Polymorphism in Children with Premature Adrenarche.
AB  - Premature adrenarche (PA), the early rise in adrenal androgen production leading
      to prepubertal signs of androgen action, has been connected with adverse
      metabolic features. The metabolic syndrome is characterized by low-grade
      inflammation which in turn is associated with increases in circulating
      proinflammatory cytokines, like tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6). We tested the hypothesis that serum concentrations of TNF
      alpha and IL-6 are increased in PA by studying 73 children with PA and 98 age-
      and gender-matched controls. Serum TNF-alpha and IL-6 concentrations were
      measured using a multiplex bead array. The subjects were genotyped for the TNF
      alpha gene -308 G > A polymorphism (known to affect TNF-alpha gene
      transcription), and genotype-phenotype associations were studied. The mean serum
      TNF-alpha concentration was higher in the PA than control children (20.4 vs. 18.4
      pg/ml, P = 0.048), whereas there was no significant difference in the mean serum
      IL-6 concentrations between the study groups. The difference in TNF-alpha was not
      explained by excess body weight in the PA subjects as the difference remained
      significant after BMI-adjustment (P = 0.038). In the PA group, TNF-alpha
      concentration was not associated with metabolic-endocrine features, but high IL-6
      was associated with lower birth weight. There was no difference in the genotype
      distribution of the TNF-alpha gene -308 G > A polymorphism between the PA and
      control groups. In conclusion, PA was associated with increased serum TNF-alpha
      concentrations which, unexpectedly, were not connected with BMI or insulin
      resistance. The TNF-alpha gene -308 G > A polymorphism does not seem to be
      associated with the development of PA.

PMID- 22654785
TI  - Cognitive impairment and dementia in Parkinson's disease: clinical features,
      diagnosis, and management.
AB  - Parkinson's disease (PD) is a common, disabling, neurodegenerative disorder. In
      addition to classical motor symptoms, non-motor features are now widely accepted
      as part of the clinical picture, and cognitive decline is a very important aspect
      of the disease, as it brings an additional significant burden for the patient and
      caregivers. The diagnosis of cognitive decline in PD, namely mild cognitive
      impairment (MCI) and dementia, can be extremely challenging, remaining largely
      based on clinical and cognitive assessments. Diagnostic criteria and methods for
      PD dementia and MCI have been recently issued by expert work groups. This
      manuscript has synthesized relevant data in order to obtain a pragmatic and
      updated review regarding cognitive decline in PD, from milder stages to dementia.
      This text will summarize clinical features, diagnostic methodology, and
      therapeutic issues of clinical decline in PD. Relevant clinical genetic issues,
      including recent advances, will also be approached.

PMID- 22654789
TI  - Enhanced BRET Technology for the Monitoring of Agonist-Induced and Agonist
      Independent Interactions between GPCRs and beta-Arrestins.
AB  - The bioluminescence resonance energy transfer (BRET) technique has become
      extremely valuable for the real-time monitoring of protein-protein interactions
      in live cells. This method is highly amenable to the detection of G protein
      coupled receptor (GPCR) interactions with proteins critical for regulating their
      function, such as beta-arrestins. Of particular interest to endocrinologists is
      the ability to monitor interactions involving endocrine receptors, such as orexin
      receptor 2 or vasopressin type II receptor. The BRET method utilizes heterologous
      co-expression of fusion proteins linking one protein of interest (GPCR) to a
      bioluminescent donor enzyme, a variant of Renilla luciferase, and a second
      protein of interest (beta-arrestin) to an acceptor fluorophore. If in close
      proximity, energy resulting from oxidation of the coelenterazine substrate by the
      donor will transfer to the acceptor, which in turn fluoresces. Using novel
      luciferase constructs, we were able to monitor interactions not detectable using
      less sensitive BRET combinations in the same configuration. In particular, we
      were able to show receptor/beta-arrestin interactions in an agonist-independent
      manner using Rluc8-tagged mutant receptors, in contrast to when using Rluc.
      Therefore, the enhanced BRET methodology has not only enabled live cell compound
      screening as we have recently published, it now provides a new level of
      sensitivity for monitoring specific transient, weak or hardly detectable protein
      protein complexes, including agonist-independent GPCR/beta-arrestin interactions.
      This has important implications for the use of BRET technologies in endocrine
      drug discovery programs as well as academic research.

PMID- 22654790
TI  - Frontiers in cancer endocrinology.

PMID- 22654788
TI  - 7alpha-hydroxypregnenolone, a new key regulator of locomotor activity of
      vertebrates: identification, mode of action, and functional significance.
AB  - Steroids synthesized de novo by the central and peripheral nervous systems are
      called neurosteroids. The formation of neurosteroids from cholesterol in the
      brain was originally demonstrated in mammals by Baulieu and colleagues. Our
      studies over the past two decades have also shown that, in birds and amphibians
      as in mammals, the brain expresses several kinds of steroidogenic enzymes and
      produces a variety of neurosteroids. Thus, de novo neurosteroidogenesis from
      cholesterol is a conserved property that occurs throughout vertebrates. However,
      the biosynthetic pathways of neurosteroids in the brain of vertebrates was
      considered to be still incompletely elucidated. Recently, 7alpha
      hydroxypregnenolone was identified as a novel bioactive neurosteroid stimulating
      locomotor activity in the brain of newts and quail through activation of the
      dopaminergic system. Subsequently, diurnal and seasonal changes in synthesis of
      7alpha-hydroxypregnenolone in the brain were demonstrated. Interestingly,
      melatonin derived from the pineal gland and eyes regulates 7alpha
      hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor
      changes. Prolactin, an adenohypophyseal hormone, regulates 7alpha
      hydroxypregnenolone synthesis in the brain, and may also induce seasonal
      locomotor changes. This review highlights the identification, mode of action, and
      functional significance of 7alpha-hydroxypregnenolone, a new key regulator of
      locomotor activity of vertebrates, in terms of diurnal and seasonal changes in
      7alpha-hydroxypregnenolone synthesis, and describes some of their regulatory
      mechanisms.

PMID- 22654791
TI  - Early Diagnosis of Werner's Syndrome Using Exome-Wide Sequencing in a Single,
      Atypical Patient.
AB  - Genetic diagnosis of inherited metabolic disease is conventionally achieved
      through syndrome recognition and targeted gene sequencing, but many patients
      receive no specific diagnosis. Next-generation sequencing allied to capture of
      expressed sequences from genomic DNA now offers a powerful new diagnostic
      approach. Barriers to routine diagnostic use include cost, and the complexity of
      interpreting results arising from simultaneous identification of large numbers of
      variants. We applied exome-wide sequencing to an individual, 16-year-old daughter
      of consanguineous parents with a novel syndrome of short stature, severe insulin
      resistance, ptosis, and microcephaly. Pulldown of expressed sequences from
      genomic DNA followed by massively parallel sequencing was undertaken. Single
      nucleotide variants were called using SAMtools prior to filtering based on
      sequence quality and existence in control genomes and exomes. Of 485 genetic
      variants predicted to alter protein sequence and absent from control data, 24
      were homozygous in the patient. One mutation - the p.Arg732X mutation in the WRN
      gene - has previously been reported in Werner's syndrome (WS). On re-evaluation
      of the patient several early features of WS were detected including loss of fat
      from the extremities and frontal hair thinning. Lymphoblastoid cells from the
      proband exhibited a defective decatenation checkpoint, consistent with loss of
      WRN activity. We have thus diagnosed WS some 15 years earlier than average,
      permitting aggressive prophylactic therapy and screening for WS complications,
      illustrating the potential of exome-wide sequencing to achieve early diagnosis
      and change management of rare autosomal recessive disease, even in individual
      patients of consanguineous parentage with apparently novel syndromes.

PMID- 22654792
TI  - Molecular basis for defining the pineal gland and pinealocytes as targets for
      tumor necrosis factor.
AB  - The pineal gland, the gland that translates darkness into an endocrine signal by
      releasing melatonin at night, is now considered a key player in the mounting of
      an innate immune response. Tumor necrosis factor (TNF), the first pro
      inflammatory cytokine to be released by an inflammatory response, suppresses the
      translation of the key enzyme of melatonin synthesis (arylalkylamine-N
      acetyltransferase, Aanat). Here, we show that TNF receptors of the subtype 1 (TNF
      R1) are expressed by astrocytes, microglia, and pinealocytes. We also show that
      the TNF signaling reduces the level of inhibitory nuclear factor kappa B protein
      subtype A (NFKBIA), leading to the nuclear translocation of two NFKB dimers,
      p50/p50, and p50/RelA. The lack of a transactivating domain in the p50/p50 dimer
      suggests that this dimer is responsible for the repression of Aanat
      transcription. Meanwhile, p50/RelA promotes the expression of inducible nitric
      oxide synthase (iNOS) and the production of nitric oxide, which inhibits
      adrenergically induced melatonin production. Together, these data provide a
      mechanistic basis for considering pinealocytes a target of TNF and reinforce the
      idea that the suppression of pineal melatonin is one of the mechanisms involved
      in mounting an innate immune response.

PMID- 22654793
TI  - Using bisphenol-a to study the onset of polycystic ovarian syndrome.

PMID- 22654794
TI  - Intrinsic, Pro-Apoptotic Effects of IGFBP-3 on Breast Cancer Cells are
      Reversible: Involvement of PKA, Rho, and Ceramide.
AB  - We established previously that IGFBP-3 could exert positive or negative effects
      on cell function depending upon the extracellular matrix composition and by
      interacting with integrin signaling. To elicit its pro-apoptotic effects IGFBP-3
      bound to caveolin-1 and the beta 1 integrin receptor and increased their
      association culminating in MAPK activation. Disruption of these complexes or
      blocking the beta 1 integrin receptor reversed these intrinsic actions of IGFBP
      3. In this study we have examined the signaling pathway between integrin receptor
      binding and MAPK activation that mediates the intrinsic, pro-apoptotic actions of
      IGFBP-3. We found on inhibiting protein kinase A (PKA), Rho associated kinase
      (ROCK), and ceramide, the accentuating effects of IGFBP-3 on apoptotic triggers
      were reversed, such that IGFBP-3 then conferred cell survival. We established
      that IGFBP-3 activated Rho, the upstream regulator of ROCK and that beta1
      integrin and PKA were upstream of Rho activation, whereas the involvement of
      ceramide was downstream. The beta 1 integrin, PKA, Rho, and ceramide were all
      upstream of MAPK activation. These data highlight key components involved in the
      pro-apoptotic effects of IGFBP-3 and that inhibiting them leads to a reversal in
      the action of IGFBP-3.

PMID- 22654795
TI  - Defying the stereotype: non-canonical roles of the Peptide hormones guanylin and
      uroguanylin.
AB  - The peptide hormones uroguanylin and guanylin have been traditionally thought to
      be mediators of fluid-ion homeostasis in the vertebrate intestine. They serve as
      ligands for receptor guanylyl cyclase C (GC-C), and both receptor and ligands are
      expressed predominantly in the intestine. Ligand binding to GC-C results in
      increased cyclic GMP production in the cell which governs downstream signaling.
      In the last decade, a significant amount of research has unraveled novel
      functions for this class of peptide hormones, in addition to their action as
      intestinal secretagogues. An additional receptor for uroguanylin, receptor
      guanylyl cyclase D, has also been identified. Thus, unconventional roles of these
      peptides in regulating renal filtration, olfaction, reproduction, and cell
      proliferation have begun to be elucidated in detail. These varied effects suggest
      that these peptide hormones act in an autocrine, paracrine as well as endocrine
      manner to regulate diverse cellular processes.

PMID- 22654796
TI  - Partitioning of bronchopulmonary carcinoids in two different prognostic
      categories by ki-67 score.
AB  - INTRODUCTION: Histological distinction between typical and atypical
      bronchopulmonary carcinoids is based on mitotic activity and necrosis. Regardless
      of these two parameters, outcome after surgery is often unpredictable. In this
      study the prognostic value of different clinico-pathological factors was
      retrospectively analyzed in a large series of patients with bronchopulmonary
      carcinoid. MATERIALS AND METHODS: The long-term post-surgical outcome of 106
      radically treated patients affected by bronchopulmonary carcinoid from two
      Italian centers was correlated with tumor characteristics assessed by combining
      conventional histology with a panel of immunohistochemical markers of
      neuroendocrine differentiation (chromogranin-A, NSE) and proliferation activity
      (Ki-67 score). RESULTS: Carcinoids were assessed as typical (TC = 75; 70.8%) and
      atypical (AC = 31; 29.2%). Mean follow-up was 8.3 years (range: 0-20; median:
      8.0). All cases expressed neuroendocrine markers. At univariate analysis, tumor
      recurrence [14/75 TC (18.7%), 15/31 AC (48.4%)] correlated with carcinoid
      histotype (P = 0.003), tumor size (P = 0.012), mitotic index (P = 0.044), Ki-67
      score (P < 0.0001), and synchronous node metastasis (P = 0.037). Of these, Cox
      multivariate analysis confirmed only Ki-67 score as independent predictor of
      disease recurrence (P = 0.009). The best cut-off for Ki-67 score (calculated by
      ROC curves) discriminating recurrent vs non-recurrent disease was 4% (sensitivity
      79.3%; specificity 83.8%; area under the curve 0.85). By stratifying patients
      according to this cut-off, a significantly different disease-free survival was
      found (log-rank test P < 0.0001). CONCLUSION: Ki-67 score accurately separates
      bronchopulmonary carcinoids in two well-distinct histo-prognostic categories. Ki
      67 score predicts the patients outcome better than mitotic count, histotype, and
      tumor stage and it is therefore helpful in establishing the appropriate follow
      up.

PMID- 22654797
TI  - Estradiol meets notch signaling in developing neurons.
AB  - The transmembrane receptor Notch, a master developmental regulator, controls
      gliogenesis, neurogenesis, and neurite development in the nervous system.
      Estradiol, acting as a hormonal signal or as a neurosteroid, also regulates these
      developmental processes. Here we review recent evidence indicating that estradiol
      and Notch signaling interact in developing hippocampal neurons by a mechanism
      involving the putative membrane receptor G protein-coupled receptor 30. This
      interaction is relevant for the control of neuronal differentiation, since the
      downregulation of Notch signaling by estradiol results in the upregulation of
      neurogenin 3, which in turn promotes dendritogenesis.

PMID- 22654798
TI  - Glucocorticoid-induced osteoporosis - a disorder of mesenchymal stromal cells?
AB  - Glucocorticoids are a class of steroid hormones that are essential to life but
      cause serious harm in excess. The main clinical features of glucocorticoid excess
      are due to adverse effects on cells and tissues that arise from a common
      developmental precursor - the mesenchymal stromal cell (MSC; sometimes referred
      to as the mesenchymal stem cell). Interestingly glucocorticoids appear essential
      for the differentiation of cells and tissues that arise from MSCs. High levels of
      glucocorticoids are used in tissue engineering strategies to enhance the
      formation of tissues such as bone, cartilage, and muscle. This article discusses
      the paradox that glucocorticoids both enhance and impair MSC development and
      function. It will describe how endogenous glucocorticoids are likely to be
      important in these processes in vivo and will discuss the implications for
      therapies aimed at reducing the damage associated with the use of therapeutic
      glucocorticoids.

PMID- 22654799
TI  - Sunitinib Inhibits Cell Proliferation and Alters Steroidogenesis by Down
      Regulation of HSD3B2 in Adrenocortical Carcinoma Cells.
AB  - The multi-tyrosine kinase inhibitor sunitinib is used in the treatment of several
      solid tumors. Animal experiments pointed to an adrenotoxic effect of sunitinib.
      Therefore, we evaluated the expression of key targets of sunitinib in human
      adrenocortical carcinoma (ACC) tumor samples and investigated its in vitro
      effects in ACC cell lines. We carried out immunohistochemistry for vascular
      endothelial growth factor (VEGF) and its receptor (VEGF-R2) in 157 ACC samples
      and nine normal adrenal glands. VEGF and VEGF-R2 protein were expressed in 72 and
      99% of ACC samples, respectively. Using NCI-H295 and SW13 ACC cell lines, we
      investigated the effects of sunitinib on cell proliferation. Sunitinib reduced
      dose-dependently cell viability of both NCI-H295 and SW13 cells (SW13: 0.1 MUM 96
      +/- 7%, 1 MUM 90 +/- 9%*, 5 MUM 62 +/- 6%*, controls 100 +/- 9%; *p < 0.05). To
      determine sunitinib effects on steroidogenesis, we measured steroid hormones in
      cell culture supernatant by gas chromatography-mass spectrometry. We observed a
      pronounced decrease of cortisol secretion (1 MUM 90.1 +/- 1.5%*, 5 MUM 57.2 +/-
      0.3%*, controls 100 +/- 2.4%) and a concomitant increase in the DHEA/4
      androstenedione and 17-hydroxypregnenolone/17-hydroxyprogesterone ratios,
      indicating specific inhibition of 3beta-hydroxysteroid dehydrogenase (HSD3B2). In
      yeast microsomes transformed with HSD3B2, no direct inhibition of HSD3B2 by
      sunitinib was detected. Sunitinib induced down-regulation of HSD3B2 mRNA and
      protein in ACC cell lines (mRNA: 1 MUM 44 +/- 16%*; 5 MUM 22 +/- 2%*; 10 MUM 19
      +/- 4%*; protein: 1 MUM 82 +/- 8%; 5 MUM 63 +/- 8%*; 10 MUM 55 +/- 9%*). CYP11B1
      was down-regulated at mRNA but not at protein level and CYP11A1 remained
      unchanged. In conclusion, target molecules of sunitinib are expressed in the vast
      majority of ACC samples. Sunitinib exhibits anti-proliferative effects in vitro,
      and appears to specifically block adrenal steroidogenesis by down-regulation of
      HSD3B2, rendering it a promising option for treatment of ACC.

PMID- 22654800
TI  - Estradiol synthesis and action at the synapse: evidence for "synaptocrine"
      signaling.
AB  - Classically, the modulation of brain function and behavior by steroid hormones
      was linked exclusively to secretion by peripheral endocrine glands. Subsequently,
      steroid actions within the brain were shown dependent upon either synthesis and
      secretion by peripheral organs or by production within the CNS itself using
      peripheral sources of precursors. Discovery of the estrogen-synthetic enzyme
      aromatase in brain further bolstered the latter view and served as a catalyst for
      expanding concepts of neurosteroidogenesis. In parallel research, several
      steroids, including estradiol, were found to have rapid effects on neuronal
      excitability, partially explained by novel actions at neuronal membranes. Recent
      findings from multiple levels of analysis and labs necessitate an updated view on
      how steroids are delivered to neural circuits. There is now considerable evidence
      for expression of the aromatase enzyme within synaptic boutons in the vertebrate
      CNS. Furthermore, additional work now directly couples rapid regulation of
      neuroestrogen synthesis with neurophysiological and behavioral outcomes. In this
      review we summarize evidence for targeted and acute synaptic estrogen synthesis
      and perisynaptic estrogen actions in the CNS of songbirds. We evaluate these
      findings in the context of criteria associated with classic neuromodulatory
      signaling. We term this novel form of signaling "synaptocrine," and discuss its
      implications.

PMID- 22654801
TI  - Ghrelin Receptor in Two Species of Anuran Amphibian, Bullfrog (Rana catesbeiana),
      and Japanese Tree Frog (Hyla japonica).
AB  - We have identified cDNA encoding a functional growth hormone secretagogue
      receptor 1a (GHS-R1a, ghrelin receptor) in two species of anuran amphibian, the
      bullfrog (Rana catesbeiana), and the Japanese tree frog (Hyla japonica). Deduced
      receptor protein for bullfrog and Japanese tree frog (tree frog) was comprised of
      374- and 371-amino acids, respectively. The two receptors shared 86% identity,
      and are grouped to the clade of the tetrapod homologs by phylogenetic analysis.
      In functional analyses, ghrelin and GHS-R1a agonists increased intracellular
      Ca(2+) concentration in GHS-R1a-transfected-HEK293 cell, but ligand selectivity
      of ghrelin with Ser(3) and Thr(3) was not observed between the two receptors.
      Bullfrog GHS-R1a mRNA was mainly expressed in the brain, stomach, and testis. In
      the brain, the gene expression was detected in the diencephalon and
      mesencephalon, but not in the pituitary. Tree frog GHS-R1a mRNA was predominantly
      expressed in the gastrointestinal tract and ovary, but not detected in the
      pituitary. In bullfrog stomach but not the brain, GHS-R1a mRNA expression
      increased after 10 days of fasting. For tree frog, GHS-R1a mRNA expression was
      increased in the brain, stomach and ventral skin by 10 days of fasting, and in
      the stomach and ventral skin by a dehydration treatment. Intracerebroventricular
      injection of ghrelin in dehydrated tree frog did not affect water absorption from
      the ventral skin. These results suggest that ghrelin is involved in energy
      homeostasis and possibly in osmoregulation in frogs.

PMID- 22654802
TI  - The intricate role of growth hormone in metabolism.
AB  - Growth hormone (GH), a master regulator of somatic growth, also regulates
      carbohydrate and lipid metabolism via complex interactions with insulin and
      insulin-like growth factor-1 (IGF-1). Data from human and rodent studies reveal
      the importance of GH in insulin synthesis and secretion, lipid metabolism and
      body fat remodeling. In this review, we will summarize the tissue-specific
      metabolic effects of GH, with emphasis on recent targets identified to mediate
      these effects. Furthermore, we will discuss what role GH plays in obesity and
      present possible mechanisms by which this may occur.

PMID- 22654804
TI  - A gonadotropin-releasing hormone-like molecule modulates the activity of diverse
      central neurons in a gastropod mollusk, aplysia californica.
AB  - In vertebrates, gonadotropin-releasing hormone (GnRH) is a crucial decapeptide
      that activates the hypothalamic-pituitary-gonadal axis to ensure successful
      reproduction. Recently, a GnRH-like molecule has been isolated from a gastropod
      mollusk, Aplysia californica. This GnRH (ap-GnRH) is deduced to be an
      undecapeptide, and its function remains to be explored. Our previous study
      demonstrated that ap-GnRH did not stimulate a range of reproductive parameters.
      Instead, it affected acute behavioral and locomotive changes unrelated to
      reproduction. In this study, we used electrophysiology and retrograde tracing to
      further explore the central role of ap-GnRH. Sharp-electrode intracellular
      recordings revealed that ap-GnRH had diverse effects on central neurons that
      ranged from excitatory, inhibitory, to the alteration of membrane potential.
      Unexpectedly, extracellular recordings revealed that ap-GnRH suppressed the onset
      of electrical afterdischarge in bag cell neurons, suggesting an inhibitory effect
      on female reproduction. Lastly, using immunocytochemistry coupled with nickel
      backfill, we demonstrated that some ap-GnRH neurons projected to efferent nerves
      known to innervate the foot and parapodia, suggesting ap-GnRH may directly
      modulate the motor output of these peripheral tissues. Overall, our results
      suggested that in A. californica, ap-GnRH more likely functioned as a central
      modulator of complex behavior and motor regulation rather than as a conventional
      reproductive stimulator.

PMID- 22654803
TI  - Male/Female differences in neuroprotection and neuromodulation of brain dopamine.
AB  - The existence of a sex difference in Parkinson's disease (PD) is observed as
      related to several variables, including susceptibility of the disease, age at
      onset, and symptoms. These differences between men and women represent a
      significant characteristic of PD, which suggest that estrogens may exert
      beneficial effects against the development and the progression of the disease.
      This paper reviews the neuroprotective and neuromodulator effects of 17beta
      estradiol and progesterone as compared to androgens in the nigrostriatal
      dopaminergic (NSDA) system of both female and male rodents. The 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) mice model of PD and methamphetamine toxicity
      faithfully reproduce the sex differences of PD in that endogenous estrogen levels
      appear to influence the vulnerability to toxins targeting the NSDA system.
      Exogenous 17beta-estradiol and/or progesterone treatments show neuroprotective
      properties against NSDA toxins while androgens fail to induce any beneficial
      effect. Sex steroid treatments show male and female differences in their
      neuroprotective action against methamphetamine toxicity. NSDA structure and
      function, as well as the distribution of estrogen receptors, show sex differences
      and may influence the susceptibility to the toxins and the response to sex
      steroids. Genomic and non-genomic actions of 17beta-estradiol converge to promote
      survival factors and the presence of both estrogen receptors alpha and beta are
      critical to 17beta-estradiol neuroprotective action against MPTP toxicity.

PMID- 22654805
TI  - Role of anticonvulsant and antiepileptogenic neurosteroids in the pathophysiology
      and treatment of epilepsy.
AB  - This review highlights the role of major endogenous neurosteroids in seizure
      disorders and the promise of neurosteroid replacement therapy in epilepsy.
      Neurosteroids are endogenous modulators of seizure susceptibility. Neurosteroids
      such as allopregnanolone (3alpha-hydroxy-5alpha-pregnane-20-one) and
      allotetrahydrodeoxycorticosterone (3alpha,21-dihydroxy-5alpha-pregnan-20-one) are
      positive modulators of GABA-A receptors. Aside from peripheral tissues,
      neurosteroids are synthesized within the brain, mostly in principal neurons.
      Neurosteroids potentiate synaptic GABA-A receptor function and also activate
      delta-subunit-containing extrasynaptic GABA-A receptors that mediate tonic
      currents and thus may play an important role in neuronal network excitability and
      seizure susceptibility. Our studies over the past decade have shown that
      neurosteroids are broad-spectrum anticonvulsants and confer seizure protection in
      various animal models. They protect against seizures induced by GABA-A receptor
      antagonists, 6-Hz model, pilocarpine-induced limbic seizures, and seizures in
      kindled animals. Unlike benzodiazepines, tolerance does not occur to their
      actions during chronic administration. Our recent studies provide compelling
      evidence that neurosteroids may have antiepileptogenic properties. There is
      emerging evidence that endogenous neurosteroids may play a key role in the
      pathophysiology of catamenial epilepsy, stress-sensitive seizure conditions,
      temporal lobe epilepsy, and alcohol-withdrawal seizures. It is suggested that
      neurosteroid replacement with natural or synthetic neurosteroids may be useful in
      the treatment of epilepsy. Synthetic analogs of neurosteroids that are devoid of
      hormonal side effects show promise in the treatment of diverse seizure disorders.
      Agents that stimulate endogenous production of neurosteroids may also be useful
      for treatment of epilepsy.

PMID- 22654807
TI  - Behavioral analysis of genetically modified mice indicates essential roles of
      neurosteroidal estrogen.
AB  - Aromatase in the mouse brain is expressed only in the nerve cells of specific
      brain regions with a transient peak during the neonatal period when sexual
      behaviors become organized. The aromatase-knockout (ArKO) mouse, generated to
      shed light on the physiological functions of estrogen in the brain, exhibited
      various abnormal behaviors, concomitant with undetectable estrogen and increased
      androgen in the blood. To further elucidate the effects of neurosteroidal
      estrogens on behavioral phenotypes, we first prepared an brain-specific aromatase
      transgenic (bsArTG) mouse by introduction of a human aromatase transgene
      controlled under a -6.5 kb upstream region of the brain-specific promoter of the
      mouse aromatase gene into fertilized mouse eggs, because the -6.5 kb promoter
      region was previously shown to contain the minimal essential element responsible
      for brain-specific spatiotemporal expression. Then, an ArKO mouse expressing the
      human aromatase only in the brain was generated by crossing the bsArTG mouse with
      the ArKO mouse. The resulting mice (ArKO/bsArTG mice) nearly recovered from
      abnormal sexual, aggressive, and locomotive (exploratory) behaviors, in spite of
      having almost the same serum levels of estrogen and androgen as the adult ArKO
      mouse. These results suggest that estrogens locally synthesized in the specific
      neurons of the perinatal mouse brain directly act on the neurons and play crucial
      roles in the organization of neuronal networks participating in the control of
      sexual, aggressive, and locomotive (exploratory) behaviors.

PMID- 22654806
TI  - Measurement of steroid concentrations in brain tissue: methodological
      considerations.
AB  - It is well recognized that steroids are synthesized de novo in the brain
      (neurosteroids). In addition, steroids circulating in the blood enter the brain.
      Steroids play numerous roles in the brain, such as influencing neural
      development, adult neuroplasticity, behavior, neuroinflammation, and
      neurodegenerative diseases such as Alzheimer's disease. In order to understand
      the regulation and functions of steroids in the brain, it is important to
      directly measure steroid concentrations in brain tissue. In this brief review, we
      discuss methods for the detection and quantification of steroids in the brain. We
      concisely present the major advantages and disadvantages of different technical
      approaches at various experimental stages: euthanasia, tissue collection, steroid
      extraction, steroid separation, and steroid measurement. We discuss, among other
      topics, the potential effects of anesthesia and saline perfusion prior to tissue
      collection; microdissection via Palkovits punch; solid phase extraction;
      chromatographic separation of steroids; and immunoassays and mass spectrometry
      for steroid quantification, particularly the use of mass spectrometry for
      "steroid profiling." Finally, we discuss the interpretation of local steroid
      concentrations, such as comparing steroid levels in brain tissue with those in
      the circulation (plasma vs. whole blood samples; total vs. free steroid levels).
      We also present reference values for a variety of steroids in different brain
      regions of adult rats. This brief review highlights some of the major
      methodological considerations at multiple experimental stages and provides a
      broad framework for designing studies that examine local steroid levels in the
      brain as well as other steroidogenic tissues, such as thymus, breast, and
      prostate.

PMID- 22654808
TI  - Wired on steroids: sexual differentiation of the brain and its role in the
      expression of sexual partner preferences.
AB  - The preference to seek out a sexual partner of the opposite sex is robust and
      ensures reproduction and survival of the species. Development of female-directed
      partner preference in the male is dependent on exposure of the developing brain
      to gonadal steroids synthesized during critical periods of sexual differentiation
      of the central nervous system. In the absence of androgen exposure, a male
      directed partner preference develops. The development and expression of sexual
      partner preference has been extensively studied in rat, ferret, and sheep model
      systems. From these models it is clear that gonadal testosterone, often through
      estrogenic metabolites, cause both masculinization and defeminization of behavior
      during critical periods of brain development. Changes in the steroid environment
      during these critical periods result in atypical sexual partner preference. In
      this manuscript, we review the major findings which support the hypothesis that
      the organizational actions of sex steroids are responsible for sexual
      differentiation of sexual partner preferences in select non-human species. We
      also explore how this information has helped to frame our understanding of the
      biological influences on human sexual orientation and gender identity.

PMID- 22654810
TI  - Regulatory Role of PBAN in Sex Pheromone Biosynthesis of Heliothine Moths.
AB  - Both males and females of heliothine moths utilize sex-pheromones during the
      mating process. Females produce and release a sex pheromone for the long-range
      attraction of males for mating. Production of sex pheromone in females is
      controlled by the peptide hormone (pheromone biosynthesis activating
      neuropeptide, PBAN). This review will highlight what is known about the role PBAN
      plays in controlling pheromone production in female moths. Male moths produce
      compounds associated with a hairpencil structure associated with the aedaegus
      that are used as short-range aphrodisiacs during the mating process. We will
      discuss the role that PBAN plays in regulating male production of hairpencil
      pheromones.

PMID- 22654811
TI  - Hypothalamic obesity in patients with craniopharyngioma: profound changes of
      several weight regulatory circuits.
AB  - One of the most striking examples of dysfunctional hypothalamic signaling of
      energy homeostasis is observed in patients with hypothalamic lesions leading to
      hypothalamic obesity (HO). This drastic condition is frequently seen in patients
      with craniopharyngioma (CP), an embryological tumor located in the hypothalamic
      and/or pituitary region, frequently causing not only hypopituitarism, but also
      leading to damage of medial hypothalamic nuclei due to the tumor and its
      treatment. HO syndrome in CP patients is characterized by fatigue, decreased
      physical activity, uncontrolled appetite, and morbid obesity, and is associated
      with insulin and leptin resistance. Mechanisms leading to the profoundly
      disturbed energy homeostasis are complex. This review summarizes different
      aspects of important clinical studies as well as data obtained in rodent studies.
      In addition a model is provided describing how medial hypothalamic lesion can
      interact simultaneously with several weight-regulating circuitries.

PMID- 22654812
TI  - Biological roles and therapeutic potential of hydroxy-carboxylic Acid receptors.
AB  - In the recent past, deorphanization studies have described intermediates of
      energy metabolism to activate G protein-coupled receptors and to thereby regulate
      metabolic functions. GPR81, GPR109A, and GPR109B, formerly known as the nicotinic
      acid receptor family, are encoded by clustered genes and share a high degree of
      sequence homology. Recently, hydroxy-carboxylic acids were identified as
      endogenous ligands of GPR81, GPR109A, and GPR109B, and therefore these receptors
      have been placed into a novel receptor family of hydroxy-carboxylic acid (HCA)
      receptors. The HCA(1) receptor (GPR81) is activated by the glycolytic metabolite
      2-hydroxy-propionic acid (lactate), the HCA(2) receptor is activated by the
      ketone body 3-hydroxy-butyric acid, and the HCA(3) receptor (GPR109B) is a
      receptor for the beta-oxidation intermediate 3-hydroxy-octanoic acid. While
      HCA(1) and HCA(2) receptors are present in most mammalian species, the HCA(3)
      receptor is exclusively found in humans and higher primates. HCA receptors are
      expressed in adipose tissue and mediate anti-lipolytic effects in adipocytes
      through G(i)-type G protein-dependent inhibition of adenylyl cyclase. HCA(2) and
      HCA(3) inhibit lipolysis during conditions of increased beta-oxidation such as
      prolonged fasting, whereas HCA(1) mediates the anti-lipolytic effects of insulin
      in the fed state. As HCA(2) is a receptor for the established anti-dyslipidemic
      drug nicotinic acid, HCA(1) and HCA(3) also represent promising drug targets and
      several synthetic ligands for HCA receptors have been developed. In this article,
      we will summarize the deorphanization and pharmacological characterization of HCA
      receptors. Moreover, we will discuss recent progress in elucidating the
      physiological and pathophysiological role to further evaluate the therapeutic
      potential of the HCA receptor family for the treatment of metabolic disease.

PMID- 22654809
TI  - Neurosteroids and GABA-A Receptor Function.
AB  - Neurosteroids represent a class of endogenous steroids that are synthesized in
      the brain, the adrenals, and the gonads and have potent and selective effects on
      the GABAA-receptor. 3alpha-hydroxy A-ring reduced metabolites of progesterone,
      deoxycorticosterone, and testosterone are positive modulators of GABA(A)-receptor
      in a non-genomic manner. Allopregnanolone (3alpha-OH-5alpha-pregnan-20-one),
      5alpha-androstane-3alpha, 17alpha-diol (Adiol), and 3alpha5alpha
      tetrahydrodeoxycorticosterone (3alpha5alpha-THDOC) enhance the GABA-mediated Cl(
      ) currents acting on a site (or sites) distinct from the GABA, benzodiazepine,
      barbiturate, and picrotoxin binding sites. 3alpha5alpha-P and 3alpha5alpha-THDOC
      potentiate synaptic GABA(A)-receptor function and activate delta-subunit
      containing extrasynaptic receptors that mediate tonic currents. On the contrary,
      3beta-OH pregnane steroids and pregnenolone sulfate (PS) are GABA(A)-receptor
      antagonists and induce activation-dependent inhibition of the receptor. The
      activities of neurosteroid are dependent on brain regions and types of neurons.
      In addition to the slow genomic action of the parent steroids, the non-genomic,
      and rapid actions of neurosteroids play a significant role in the GABA(A)
      receptor function and shift in mood and memory function. This review describes
      molecular mechanisms underlying neurosteroid action on the GABA(A)-receptor, mood
      changes, and cognitive functions.

PMID- 22654813
TI  - Human brown fat and obesity: methodological aspects.
AB  - Much is known about brown adipose tissue (BAT) in rodents. Its function is to
      generate heat in response to low environmental temperatures and to diet or
      overfeeding. The knowledge about BAT in humans is still rather limited despite
      the recent rediscovery of its functionality in adults. This review highlights the
      information available on the contribution of BAT in increasing human energy
      expenditure in relation to obesity. Besides that methodological aspects will be
      discussed that need special attention in order to unravel the heat producing
      capacity of human BAT, the recruitment of the tissue, and its functionality.

PMID- 22654815
TI  - The interrelationship of estrogen receptor and GnRH in a Basal vertebrate, the
      sea lamprey.
AB  - The hypothalamic-pituitary system is considered to be a vertebrate innovation and
      seminal event that emerged prior to or during the differentiation of the
      ancestral agnathans. Lampreys are the earliest evolved vertebrates for which
      there is a demonstrated neuroendocrine system. Lampreys have three hypothalamic
      gonadotropin-releasing hormones (GnRHs; lGnRH-I, -II, and -III) and two and
      possibly three pituitary GnRH receptors involved in mediating reproductive
      processes. Estradiol is considered to be a major reproductive steroid in both
      male and female lampreys. The purpose of this study was to investigate estrogen
      receptor (ER) expression in the lamprey brain in adult sea lampreys. Expression
      of ER mRNA was confirmed in the adult lamprey brain using RT-PCR. Using
      digoxigenin (DIG)-labeled probes, ER expression was shown to yield moderate, but
      distinct reaction products in specific neuronal nuclei of the lamprey brain,
      including the olfactory lobe, hypothalamus, habenular area, and hindbrain.
      Expression of ER in the hypothalamic area of the brain provides evidence of
      potential interaction between estradiol and GnRH(s), and is consistent with
      previous evidence showing estrogen feedback on GnRH in adult lamprey brain.
      Earlier studies have reported that there is a close distribution of glutamic acid
      decarboxylase (GAD; GABA-synthesizing enzyme) and lamprey GnRH in the preoptic
      region in adult lampreys. The establishment of a direct estradiol-kisspeptin-GABA
      GnRH interaction in lamprey has yet to be determined and will require future
      functional and co-localization studies. The phylogenetic position of lampreys as
      a basal vertebrate allows lampreys to be a basis for understanding the molecular
      evolution of the neuroendocrine system that arose in the vertebrates.

PMID- 22654814
TI  - Neurosteroids as neuromodulators in the treatment of anxiety disorders.
AB  - Anxiety disorders are the most common psychiatric disorders. They are frequently
      treated with benzodiazepines, which are fast acting highly effective anxiolytic
      agents. However, their long-term use is impaired by tolerance development and
      abuse liability. In contrast, antidepressants such as selective serotonin
      reuptake inhibitors (SSRIs) are considered as first-line treatment but have a
      slow onset of action. Neurosteroids are powerful allosteric modulators of GABA(A)
      and glutamate receptors. However, they also modulate sigma receptors and they are
      modulated themselves by SSRIs. Both pre-clinical and clinical studies have shown
      that neurosteroid homeostasis is altered in depression and anxiety disorders and
      antidepressants may act in part through restoring neurosteroid disbalance.
      Moreover, novel drugs interfering with neurosteroidogenesis such as ligands of
      the translocator protein (18 kDa) may represent an attractive pharmacological
      option for novel anxiolytics which lack the unwarranted side effects of
      benzodiazepines. Thus, neurosteroids are important endogenous neuromodulators for
      the physiology and pathophysiology of anxiety and they may constitute a novel
      therapeutic approach in the treatment of these disorders.

PMID- 22654816
TI  - The Proctolin Gene and Biological Effects of Proctolin in the Blood-Feeding Bug,
      Rhodnius prolixus.
AB  - We have reinvestigated the possible presence or absence of the pentapeptide
      proctolin in Rhodnius prolixus and report here the cloning of the proctolin cDNA.
      The transcript is expressed in the central nervous system (CNS) and some
      peripheral tissues. The proctolin prepropeptide encodes a single copy of
      proctolin along with a possible proctolin-precursor-associated peptide. We have
      biochemically identified proctolin in CNS extracts and shown its distribution
      using proctolin-like immunoreactivity. Immunostained processes are found on the
      salivary glands, female and male reproductive tissues, and heart and associated
      alary muscles. Proctolin-like immunoreactive bipolar neurons are found on the
      lateral margins of the common oviduct and bursa. Proctolin is biologically active
      on R. prolixus tissues, stimulating increases in contraction of anterior midgut
      and hindgut muscles, and increasing heartbeat frequency. Contrary to the previous
      suggestion that proctolin is absent from R. prolixus, proctolin is indeed present
      and biologically active in this medically important bug.

PMID- 22654817
TI  - Hypothalamic obesity after craniopharyngioma: mechanisms, diagnosis, and
      treatment.
AB  - Obesity is a common complication after craniopharyngioma therapy, occurring in up
      to 75% of survivors. Its weight gain is unlike that of normal obesity, in that it
      occurs even with caloric restriction, and attempts at lifestyle modification are
      useless to prevent or treat the obesity. The pathogenesis of this condition
      involves the inability to transduce afferent hormonal signals of adiposity, in
      effect mimicking a state of CNS starvation. Efferent sympathetic activity drops,
      resulting in malaise and reduced energy expenditure, and vagal activity
      increases, resulting in increased insulin secretion and adipogenesis. Lifestyle
      intervention is essentially useless in this syndrome, termed "hypothalamic
      obesity." Pharmacologic treatment is also difficult, consisting of adrenergics to
      mimic sympathetic activity, or suppression of insulin secretion with octreotide,
      or both. Recently, bariatric surgery (Roux-en-Y gastric bypass, laparoscopic
      gastric banding, truncal vagotomy) have also been attempted with variable
      results. Early and intensive management is required to mitigate the obesity and
      its negative consequences.

PMID- 22654818
TI  - Biosynthesis, mode of action, and functional significance of neurosteroids in the
      purkinje cell.
AB  - The brain has traditionally been considered to be a target site of peripheral
      steroid hormones. In addition to this classical concept, we now know that the
      brain has the capacity to synthesize steroids de novo from cholesterol, the so
      called "neurosteroids." In the middle 1990s, the Purkinje cell, an important
      cerebellar neuron, was identified as a major site for neurosteroid formation in
      the brain of mammals and other vertebrates. This discovery has provided the
      opportunity to understand neuronal neurosteroidogenesis in the brain. In
      addition, biological actions of neurosteroids are becoming clear by the studies
      using the Purkinje cell, an excellent cellular model, which is known to play an
      important role in memory and learning processes. Based on the studies on mammals
      over the past decade, it is considered that the Purkinje cell actively
      synthesizes progesterone and estradiol from cholesterol during neonatal life,
      when cerebellar neuronal circuit formation occurs. Both progesterone and
      estradiol promote dendritic growth, spinogenesis, and synaptogenesis via each
      cognate nuclear receptor in the developing Purkinje cell. Such neurosteroid
      actions mediated by neurotrophic factors may contribute to the formation of
      cerebellar neuronal circuit during neonatal life. 3alpha,5alpha
      Tetrahydroprogesterone (allopregnanolone), a progesterone metabolite, is also
      synthesized in the cerebellum and considered to act as a survival factor of
      Purkinje cells in the neonate. This review summarizes the current knowledge
      regarding the biosynthesis, mode of action, and functional significance of
      neurosteroids in the Purkinje cell during development in terms of synaptic
      formation of cerebellar neuronal networks.

PMID- 22654820
TI  - The genetics of brown adipocyte induction in white fat depots.
AB  - Evidence that adult humans have functional brown adipose tissue has stirred
      interest in the possibility that the impressive effectiveness of induction of
      brown adipocytes to reduce obesity in mice may be translated to the human
      condition. A major focus recently on the identification of signaling and
      transcription factor that stimulate the induction of brown adipocytes has come
      from transgenic and gene KO models. However, these models have created a very
      complex picture of the regulatory mechanisms for brown fat induction. In this
      review insights into the critical regulatory pathways involved in brown adipocyte
      induction in the retroperitoneal fat depot of mice are described from
      quantitative trait locus (QTL) analysis of allelic variability determining Ucp1
      levels and brown adipocyte induction in A/J vs. B6 mice. The key observation is
      that recombinant genotypes, found in recombinant inbred stains and backcross and
      intercross progeny, show transgressive variation for Ucp1 mRNA levels. These
      genetic crosses also show that the levels of Ucp1 mRNA are determined by
      interactions that control the levels of PPARalpha, PGC-1alpha, and type 2
      deiodinase (DIO2) and that each factor is controlled by a subset of QTLs that
      also control Ucp1 expression. These results indicate that induction of Ucp1 in
      the retroperitoneal fat depot involves synergy between signaling and
      transcription factors that vary depending upon the environmental conditions.
      Inherent in this model is the idea that there is a high level of redundancy that
      can involve any factor with the potential to influence expression of the core
      factors, PPARalpha, PGC-1a, and DIO2.

PMID- 22654819
TI  - Test systems to study the structure and function of uncoupling protein 1: a
      critical overview.
AB  - The discovery of active brown adipose tissue (BAT) in healthy adult humans has
      renewed interest in the biology of this organ. BAT is capable of distributing
      nutrient energy in the form of heat allowing small mammals to efficiently defend
      their body temperature when acutely exposed to the cold. On the other hand BAT
      might be a target for the treatment of obesity and related diseases, as its
      pharmacological activation could allow release of excess energy stored in white
      adipose tissue depots. Energy dissipation in BAT depends on the activity of
      uncoupling protein 1 (UCP1), therefore a BAT-based obesity therapy requires a
      detailed understanding of structure and function of UCP1. Although UCP1 has been
      in the focus of research since its discovery, central questions concerning its
      mechanistic function and regulation are not yet resolved. They have been
      addressed in native mitochondria but also in several test systems, which are
      generally used to lower inter-experimental variability and to simplify analysis
      conditions. Different test systems have contributed to our current knowledge
      about UCP1 but of course all of them have certain limitations. We here provide an
      overview about research on UCP1 structure and function in test systems. So far,
      these have nearly exclusively been employed to study rodent and not human UCP1.
      Considering that the amino acid sequence of mouse and human UCP1 is only 79%
      identical, it will be essential to test whether the human version has a similarly
      high catalytic activity, allowing a relevant amount of energy dissipation in
      human BAT. Besides the issue of comparable mechanistic function a sufficiently
      high expression level of human UCP1 is a further prerequisite for anti-obesity
      therapeutic potential. Treatments which induce BAT hyperplasia and UCP1
      expression in humans might therefore be equally important to discover as mere
      activators of the thermogenic process.

PMID- 22654821
TI  - Paternal Uniparental Isodisomy of Chromosome 11p15.5 within the Pancreas Causes
      Isolated Hyperinsulinemic Hypoglycemia.
AB  - BACKGROUND: Loss of function mutations in the genes encoding the pancreatic beta
      cell ATP-sensitive potassium (KATP) channel are identified in approximately 80%
      of patients with diazoxide unresponsive hyperinsulinemic hypoglycemia (HH). For a
      small number of patients HH can occur as part of a multisystem disease such as
      Beckwith-Wiedemann syndrome (BWS). In approximately 20% of patients, BWS results
      from chromosome 11 paternal uniparental disomy (UPD), which causes dysregulation
      of imprinted growth regulation genes at 11p15.5. There is a considerable range in
      the clinical features and phenotypic severity associated with BWS which is likely
      to be due to somatic mosaicism. The cause of HH in these patients is not known.
      RESEARCH DESIGN AND METHODS: We undertook microsatellite analysis of 12 markers
      spanning chromosome 11p in two patients with severe HH and diffuse disease
      requiring a pancreatectomy. In both patients mutations in the K(ATP) channel
      genes had not been identified. RESULTS: We identified segmental paternal UPD in
      DNA extracted from pancreatic tissue in both patients. UPD was not observed in
      DNA extracted from the patient's leukocytes or buccal samples. In both cases the
      UPD encompassed the differentially methylated region at chromosome 11p15.5.
      Despite this neither patient had any further features of BWS. CONCLUSION:
      Paternal UPD of the chromosome 11p15.5 differentially methylated region limited
      to the pancreatic tissue may represent a novel cause of isolated diazoxide
      unresponsive HH. Loss of heterozygosity studies should therefore be considered in
      all patients with severe HH who have undergone pancreatic surgery when K(ATP)
      channel mutation(s) have not been identified.

PMID- 22654822
TI  - GPR35 as a Novel Therapeutic Target.
AB  - G protein-coupled receptors (GPCRs) remain the best studied class of cell surface
      receptors and the most tractable family of proteins for novel small molecule drug
      discovery. Despite this, a considerable number of GPCRs remain poorly
      characterized and in a significant number of cases, endogenous ligand(s) that
      activate them remain undefined or are of questionable physiological relevance.
      GPR35 was initially discovered over a decade ago but has remained an "orphan"
      receptor. Recent publications have highlighted novel ligands, both endogenously
      produced and synthetic, which demonstrate significant potency at this receptor.
      Furthermore, evidence is accumulating which highlights potential roles for GPR35
      in disease and therefore, efforts to characterize GPR35 more fully and develop it
      as a novel therapeutic target in conditions that range from diabetes and
      hypertension to asthma are increasing. Recently identified ligands have shown
      marked species selective properties, indicating major challenges for future drug
      development. As we begin to understand these issues, the continuing efforts to
      identify novel agonist and antagonist ligands for GPR35 will help to decipher its
      true physiological relevance; translating multiple assay systems in vitro, to
      animal disease systems in vivo and finally to man.

PMID- 22654823
TI  - Oxidative Stress-Mediated Brain Dehydroepiandrosterone (DHEA) Formation in
      Alzheimer's Disease Diagnosis.
AB  - Neurosteroids are steroids made by brain cells independently of peripheral
      steroidogenic sources. The biosynthesis of most neurosteroids is mediated by
      proteins and enzymes similar to those identified in the steroidogenic pathway of
      adrenal and gonadal cells. Dehydroepiandrosterone (DHEA) is a major neurosteroid
      identified in the brain. Over the years we have reported that, unlike other
      neurosteroids, DHEA biosynthesis in rat, bovine, and human brain is mediated by
      an oxidative stress-mediated mechanism, independent of the cytochrome P450
      17alpha-hydroxylase/17,20-lyase (CYP17A1) enzyme activity found in the periphery.
      This alternative pathway is induced by pro-oxidant agents, such as Fe(2+) and
      beta-amyloid peptide. Neurosteroids are involved in many aspects of brain
      function, and as such, are involved in various neuropathologies, including
      Alzheimer's disease (AD). AD is a progressive, yet irreversible neurodegenerative
      disease for which there are limited means for ante-mortem diagnosis. Using brain
      tissue specimens from control and AD patients, we provided evidence that DHEA is
      formed in the AD brain by the oxidative stress-mediated metabolism of an
      unidentified precursor, thus depleting levels of the precursor in the blood
      stream. We tested for the presence of this DHEA precursor in human serum using a
      Fe(2+)-based reaction and determined the amounts of DHEA formed. Fe(2+) treatment
      of the serum resulted in a dramatic increase in DHEA levels in control patients,
      whereas only a moderate or no increase was observed in AD patients. The DHEA
      variation after oxidation correlated with the patients' cognitive and mental
      status. In this review, we present the cumulative evidence for oxidative stress
      as a natural regulator of DHEA formation and the use of this concept to develop a
      blood-based diagnostic tool for neurodegenerative diseases linked to oxidative
      stress, such as AD.

PMID- 22654824
TI  - Diagnostics, treatment, and follow-up in craniopharyngioma.
AB  - Craniopharyngiomas are partly cystic embryogenic malformations of the sellar and
      parasellar region, with up to half the 0.5-2.0 new cases per million population
      per year occur in children and adolescents. Diagnosis profile for pediatric and
      adult craniopharyngioma is characterized by a combination of headache, visual
      impairment, and polyuria/polydipsia, which can also include significant weight
      gain. In children, growth retardation, and/or premature puberty often occur later
      or postoperatively. Recommended therapy with favorable tumor localization is
      complete resection; with unfavorable tumor localization (optic nerve and/or
      hypothalamic involvement), consensus is still pending whether a limited resection
      followed by local irradiation is more prudent. Even though overall survival rates
      are high (92%), recurrences after complete resection and progressions after
      incomplete resection can be expected. Accordingly, a randomized multinational
      trial (KRANIOPHARYNGEOM 2007) has been established to identify optimal diagnosis,
      treatment (particularly the ideal time point of irradiation after incomplete
      resection), and quality of life strategies of this chronic disease - most notably
      the morbid hypothalamic obesity in ~50% of long-term survivors. We report on
      craniopharyngioma origins, its pathological manifestations, and specific
      challenges these sequelae pose regarding diagnosis, treatment, and life-long
      multi-discipline quality of life management for both adult and childhood
      craniopharyngioma patients.

PMID- 22654826
TI  - Landmarks in insulin research.
AB  - Ever since the discovery of insulin and its role in the regulation of glucose
      uptake and utilization, there has been great interest in insulin, its structure
      and the way in which it interacts with its receptor and effects signal
      transduction. As the 90th anniversary of the discovery of insulin approaches, it
      is timely to provide an overview of the landmark discoveries relating to the
      structure and function of this remarkable molecule and its receptor.

PMID- 22654828
TI  - Sexual dimorphism of kisspeptin and neurokinin B immunoreactive neurons in the
      infundibular nucleus of aged men and women.
AB  - The secretory output of gonadotropin-releasing hormone (GnRH) neurons is
      critically influenced by peptidergic neurons synthesizing kisspeptins (KP) and
      neurokinin B (NKB) in the hypothalamic infundibular nucleus (Inf). These cells
      mediate negative feedback effects of sex steroids on the reproductive axis. While
      negative feedback is lost in postmenopausal women, it is partly preserved by the
      sustained testosterone secretion in aged men. We hypothesized that the different
      reproductive physiology of aged men and women is reflected in morphological
      differences of KP and NKB neurons. This sexual dimorphism was studied with
      immunohistochemistry in hypothalamic sections of aged human male (>=50 years) and
      female (>55 years) subjects. KP and NKB cell bodies of the Inf were larger in
      females. The number of KP cell bodies, the density of KP fibers, and the
      incidence of their contacts on GnRH neurons were much higher in aged women
      compared with men. The number of NKB cell bodies was only slightly higher in
      women and there was no sexual dimorphism in the regional density of NKB fibers
      and the incidence of their appositions onto GnRH cells. The incidences of NKB
      cell bodies, fibers, and appositions onto GnRH neurons exceeded several-fold
      those of KP-IR elements in men. More NKB than KP inputs to GnRH cells were also
      present in women. Immunofluorescent studies identified only partial overlap
      between KP and NKB axons. KP and NKB were colocalized in higher percentages of
      afferents to GnRH neurons in women compared with men. Most of these sex
      differences might be explained with the lack of estrogen negative feedback in
      aged women, whereas testosterone can continue to suppress KP, and to a lesser
      extent, NKB synthesis in men. Overall, sex differences in reproductive physiology
      of aged humans were reflected in the dramatic sexual dimorphism of the KP system,
      with significantly higher incidences of KP-IR neurons, fibers and inputs to GnRH
      neurons in aged females vs. males.

PMID- 22654830
TI  - Control of Brown Adipose Tissue Glucose and Lipid Metabolism by PPARgamma.
AB  - Brown adipose tissue (BAT) non-shivering thermogenesis impacts energy homeostasis
      in rodents and humans. Mitochondrial uncoupling protein 1 in brown fat cells
      produces heat by dissipating the energy generated by fatty acid and glucose
      oxidation. In addition to thermogenesis and despite its small relative size,
      sympathetically activated BAT constitutes an important glucose, fatty acid, and
      triacylglycerol-clearing organ, and such function could potentially be used to
      alleviate dyslipidemias, hyperglycemia, and insulin resistance. To date, chronic
      sympathetic innervation and peroxisome proliferator-activated receptor (PPAR)
      gamma activation are the only recognized inducers of BAT recruitment. Here, we
      review the major differences between these two BAT inducers in the regulation of
      lipolysis, fatty acid oxidation, lipid uptake and triacylglycerol synthesis,
      glucose uptake, and de novo lipogenesis. Whereas BAT recruitment through
      sympathetic drive translates into functional thermogenic activity, PPARgamma
      mediated recruitment is associated with a reduction in sympathetic activity
      leading to increased lipid storage in brown adipocytes. The promising therapeutic
      role of BAT in the treatment of hypertriglyceridemic and hyperglycemic conditions
      is also discussed.

PMID- 22654829
TI  - Lumiestrone is Photochemically Derived from Estrone and may be Released to the
      Environment without Detection.
AB  - Endocrine disrupting chemicals are adversely affecting the reproductive health
      and metabolic status of aquatic vertebrates. Estrone is often the dominant
      natural estrogen in urban sewage, yet little is known about its environmental
      fate and biological effects. Increased use of UV-B radiation for effluent
      treatments, and exposure of effluents to sunlight in holding ponds led us to
      examine the effects of environmentally relevant levels of UV-B radiation on the
      photodegradation potential of estrone. Surprisingly, UV-B-mediated degradation
      leads to the photoproduction of lumiestrone, a little known 13alpha-epimer form
      of estrone. We show for the first time that lumiestrone possesses novel
      biological activity. In vivo treatment with estrone stimulated estrogen receptor
      (ER) alpha mRNA production in the male goldfish liver, whereas lumiestrone was
      without effect, suggesting a total loss of estrogenicity. In contrast, results
      from in vitro ER-dependent reporter gene assays indicate that lumiestrone showed
      relatively higher estrogenic potency with the zebrafish ERbeta2 than zfERalpha,
      suggesting that it may act through an ERbeta-selectivity. Lumiestrone also
      activated human ERs. Microarray analysis of male goldfish liver following in vivo
      treatments showed that lumiestrone respectively up- and down-regulated 20 and 69
      mRNAs, which was indicative of metabolic upsets and endocrine activities. As a
      photodegradation product from a common estrogen of both human and farm animal
      origin, lumiestrone is present in sewage effluent, is produced from estrone upon
      exposure to natural sunlight and should be considered as a new environmental
      contaminant.

PMID- 22654825
TI  - Comparative endocrinology of aging and longevity regulation.
AB  - Hormones regulate growth, development, metabolism, and other complex processes in
      multicellular animals. For many years it has been suggested that hormones may
      also influence the rate of the aging process. Aging is a multifactorial process
      that causes biological systems to break down and cease to function in adult
      organisms as time passes, eventually leading to death. The exact underlying
      causes of the aging process remain a topic for debate, and clues that may shed
      light on these causes are eagerly sought after. In the last two decades, gene
      mutations that result in delayed aging and extended longevity have been
      discovered, and many of the affected genes have been components of endocrine
      signaling pathways. In this review we summarize the current knowledge on the
      roles of endocrine signaling in the regulation of aging and longevity in various
      animals. We begin by discussing the notion that conserved systems, including
      endocrine signaling pathways, "regulate" the aging process. Findings from the
      major model organisms: worms, flies, and rodents, are then outlined. Unique
      lessons from studies of non-traditional models: bees, salmon, and naked mole
      rats, are also discussed. Finally, we summarize the endocrinology of aging in
      humans, including changes in hormone levels with age, and the involvement of
      hormones in aging-related diseases. The most well studied and widely conserved
      endocrine pathway that affects aging is the insulin/insulin-like growth factor
      system. Mutations in genes of this pathway increase the lifespan of worms, flies,
      and mice. Population genetic evidence also suggests this pathway's involvement in
      human aging. Other hormones including steroids have been linked to aging only in
      a subset of the models studied. Because of the value of comparative studies, it
      is suggested that the aging field could benefit from adoption of additional model
      organisms.

PMID- 22654827
TI  - Rapid estradiol modulation of neuronal connectivity and its implications for
      disease.
AB  - Estrogens have multiple actions in the brain including modulating synaptic
      plasticity, connectivity, and cognitive behaviors. While the classical view of
      estrogens are as endocrine signals, whose effects manifest via the regulation of
      gene transcription, mounting evidence has been presented demonstrating that
      estrogens have rapid effects within specific areas of the brain. The emergence
      that 17 beta-estradiol can be produced locally in the brain which can elicit
      rapid (within minutes) cellular responses has led to its classification as a
      neurosteroid. Moreover, recent studies have also begun to detail the molecular
      and cellular underpinnings of how 17 beta-estradiol can rapidly modulate spiny
      synapses (dendritic spines). Remodeling of dendritic spines is a key step in the
      rewiring of neuronal circuitry thought to underlie the processing and storage of
      information in the forebrain. Conversely, abnormal remodeling of dendritic spines
      is thought to contribute to a number of psychiatric and neurodevelopmental
      disorders. Here we review recent molecular and cellular work that offers a
      potential mechanism of how 17 beta-estradiol may modulate synapse structure and
      function of cortical neurons. This mechanism allows cortical neurons to respond
      to activity-dependent stimuli with greater efficacy. In turn this form of
      plasticity may provide an insight into how 17 beta-estradiol can modulate the
      rewiring of neuronal circuits, underlying its ability to influencing cortically
      based behaviors. We will then go on to discuss the potential role of 17 beta
      estradiol modulation of neural circuits and its potential relevance for the
      treatment of psychiatric and neurodevelopmental disorders.

PMID- 22654831
TI  - Differentiation of Human Adipose-Derived Stem Cells into "Brite" (Brown-in-White)
      Adipocytes.
AB  - It is well established now that adult humans possess active brown adipose tissue
      (BAT) which represents a potential pharmacological target to combat obesity and
      associated diseases. Moreover thermogenic brown-like adipocytes ("brite
      adipocytes") appear also in mouse white adipose tissue (WAT) upon beta3
      adrenergic stimulation. We had previously shown that human multipotent adipose
      derived stem cells (hMADS) are able to differentiate into cells which exhibit the
      key properties of human white adipocytes, and then to convert into functional
      brown adipocytes upon PPARgamma activation. In light of a wealth of data
      indicating that thermogenic adipocytes from BAT and WAT have a distinct cellular
      origin, we have characterized at the molecular level UCP1 positive hMADS
      adipocytes from both sexes as brite adipocytes. Conversion of white to brown
      hMADS adipocytes is dependent on PPARgamma activation with rosiglitazone as the
      most potent agonist and is inhibited by a PPARgamma antagonist. In contrast to
      mouse cellular models, hMADS cells conversion into brown adipocytes is weakly
      induced by BMP7 treatment and not modulated by activation of the Hedgehog
      pathway. So far no primary or clonal precursor cells of human brown adipocytes
      have been obtained that can be used as a tool to develop therapeutic drugs and to
      gain further insights into the molecular mechanisms of brown adipogenesis in
      humans. Thus hMADS cells represent a suitable human cell model to delineate the
      formation and/or the uncoupling capacity of brown/brite adipocytes that could
      help to dissipate caloric excess intake among individuals.

PMID- 22654834
TI  - Effects of Acute Recombinant Human TSH on Serum Ghrelin Levels.
AB  - Recent findings showed the presence of a reciprocal relationship between thyroid
      hormones and ghrelin, although the exact mechanism is not known. DESIGN: Our
      study is addressed to evaluate the effect of acute exogenous rhTSH administration
      on serum ghrelin levels in athyreotic patients on replacement l-thyroxine
      therapy. The study group included 50 patients (16 males and 34 females) submitted
      to total thyroidectomy and 131-iodine remnant ablation for differentiated thyroid
      cancer on l-thyroxine therapy. Mean age was 47.5 +/- 16.5 years and mean BMI was
      25.6 +/- 5.01 kg/m(2). rhTSH was administrated at the dosage of 0.9 mg i.m. once
      daily for two consecutive days. Blood samples were taken between 08.00 and 09.00
      after a overnight fasting for measurement of TSH, FT3, FT4, and ghrelin before
      the first administration of rhTSH and for measurement of TSH and ghrelin 24, 48,
      72, and 96 h after the first administration of rhTSH. RESULTS: Mean +/- SD values
      of basal TSH were 0.54 +/- 0.77 MUU/ml without significant difference between
      females and males. As expected, after rhTSH administration TSH concentrations
      increased at 24 and 48 h with peak TSH values ranging from 20.20 to 313 MUU/ml
      (mean +/- SD 98.4 +/- 66.7 MUU/ml). Mean +/- SD values of basal ghrelin were 1085
      +/- 373 pg/ml without significant difference between males and females. After
      rhTSH administration ghrelin concentrations decreased significantly (p < 0.01) at
      24 h (mean +/- SD 934 +/- 314 pg/ml p < 0.01) and returned to pre-treatment
      levels at 96 h. CONCLUSION: Our study demonstrates that acute exogenous TSH
      administration has a suppressive effect on ghrelin secretion independent from
      changes in thyroid status.

PMID- 22654832
TI  - The Neurosteroid Progesterone Underlies Estrogen Positive Feedback of the LH
      Surge.
AB  - Our understanding the steroid regulation of neural function has rapidly evolved
      in the past decades. Not long ago the prevailing thoughts were that peripheral
      steroid hormones carried information to the brain which passively responded to
      these steroids. These steroid actions were slow, taking hours to days to be
      realized because they regulated gene expression. Over the past three decades,
      discoveries of new steroid receptors, rapid membrane-initiated signaling
      mechanisms, and de novo neurosteroidogenesis have shed new light on the
      complexity of steroids actions within the nervous system. Sexual differentiation
      of the brain during development occurs predominately through timed steroid
      mediated expression of proteins and long term epigenetic modifications. In
      contrast across the estrous cycle, estradiol release from developing ovarian
      follicles initially increases slowly and then at proestrus increases rapidly.
      This pattern of estradiol release acts through both classical genomic mechanisms
      and rapid membrane-initiated signaling in the brain to coordinate reproductive
      behavior and physiology. This review focuses on recently discovered estrogen
      receptor-alpha membrane signaling mechanisms that estradiol utilizes during
      estrogen positive feedback to stimulate de novo progesterone synthesis within the
      hypothalamus to trigger the luteinizing hormone (LH) surge important for
      ovulation and estrous cyclicity. The activation of these signaling pathways
      appears to be coordinated by the rising and waning of estradiol throughout the
      estrous cycle and integral to the negative and positive feedback mechanisms of
      estradiol. This differential responsiveness is part of the timing mechanism
      triggering the LH surge.

PMID- 22654833
TI  - The insulin receptor: a new target for cancer therapy.
AB  - A large body of evidences have shown that both the IGF-I receptor (IGF-IR) and
      the insulin receptor (IR) play a role in cancer development and progression. In
      particular, IR overactivation by IGF-II is common in cancer cells, especially in
      dedifferentiated/stem-like cells. In spite of these findings, until very
      recently, only IGF-IR but not IR has been considered a target in cancer therapy.
      Although several preclinical studies have showed a good anti-cancer activity of
      selective anti-IGF-IR drugs, the results of the clinical first trials have been
      disappointing. In fact, only a small subset of malignant tumors has shown an
      objective response to these therapies. Development of resistance to anti-IGF-IR
      drugs may include upregulation of IR isoform A (IR-A) in cancer cells and its
      overactivation by increased secretion of autocrine IGF-II. These findings have
      led to the concept that co-targeting IR together with IGF-IR may increase therapy
      efficacy and prevent adaptive resistance to selective anti-IGF-IR drugs. IR
      blockade should be especially considered in tumors with high IR-A:IGF-IR ratio
      and high levels of autocrine IGF-II. Conversely, insulin sensitizers, which
      ameliorate insulin resistance associated with metabolic disorders and cancer
      treatments, may have important implications for cancer prevention and management.
      Only few drugs co-targeting the IR and IGF-IR are currently available. Ideally,
      future IR targeting strategies should be able to selectively inhibit the tumor
      promoting effects of IR without impairing its metabolic effects.

PMID- 22654835
TI  - Genetic Defects in the Growth Hormone-IGF-I Axis Causing Growth Hormone
      Insensitivity and Impaired Linear Growth.
AB  - Human genetic defects in the growth hormone (GH)-IGF-I axis affecting the IGF
      system present with growth failure as their principal clinical feature. This is
      usually associated with GH insensitivity (GHI) presenting in childhood as severe
      or mild short stature. Dysmorphic features and metabolic abnormalities may also
      be present. The field of GHI due to mutations affecting GH action has evolved
      rapidly since the first description of the extreme phenotype related to
      homozygous GH receptor (GHR) mutations in 1966. A continuum of genetic,
      phenotypic, and biochemical abnormalities can be defined associated with
      clinically relevant defects in linear growth. The mechanisms of the GH-IGF-I axis
      in the regulation of normal human growth is discussed followed by descriptions of
      mutations in GHR, STAT5B, IGF-I, IGFALS, IGF1R, and GH1 defects causing bio
      inactive GH or anti-GH antibodies. These GH-IGF-I axis defects are associated
      with a range of clinical, and hormonal characteristics. An up-dated approach to
      the clinical assessment of the patient with GHI focusing on investigation of the
      GH-IGF-I axis and relevant molecular studies contributing to the identification
      of causative genetic defects is also discussed.

PMID- 22654836
TI  - Different approaches in radiation therapy of craniopharyngioma.
AB  - Radiation therapy is a cornerstone in the therapeutic management of
      craniopharyngioma. The close proximity to neighboring eloquent structures pose a
      particular challenge to radiation therapy. Modern treatment technologies
      including fractionated 3-D conformal radiotherapy, intensity modulated radiation
      therapy, and recently proton therapy are able to precisely cover the target while
      preserving surrounding tissue, Tumor controls between 80 and in access of 90% can
      be achieved. Alternative treatments consisting of radiosurgery, intracavitary
      application of isotopes, and brachytherapy also offer an acceptable tumor control
      and might be given in selected cases. More research is needed to establish the
      role of each treatment modality.

PMID- 22654837
TI  - beta-Adrenoceptor Signaling Networks in Adipocytes for Recruiting Stored Fat and
      Energy Expenditure.
AB  - THE ADIPOCYTE IS LIKE A BANK: a place to store excess (caloric) cash in times of
      plenty, and from which one can withdraw savings during "lean times." The beta
      adrenoceptors (betaAR) are the gateways to this mobilization of fat to be
      consumed in other tissues. This review discusses the betaAR signaling pathway(s)
      in white and brown adipocytes. Studies in rodent models show that brown
      adipocytes nestled with white fat depots correlate with and are considered a key
      enabling factor in resistance to diet-induced obesity. Since it is now recognized
      that adult humans have brown adipocytes, knowing the steps in these signaling
      pathways may provide the opportunity to manipulate adipocytes to be net consumers
      of energy.

PMID- 22654839
TI  - Role of neuroactive steroids in the peripheral nervous system.
AB  - Several reviews have so far pointed out on the relevant physiological and
      pharmacological role exerted by neuroactive steroids in the central nervous
      system. In the present review we summarize observations indicating that synthesis
      and metabolism of neuroactive steroids also occur in the peripheral nerves.
      Interestingly, peripheral nervous system is also a target of their action.
      Indeed, as here reported neuroactive steroids are physiological regulators of
      peripheral nerve functions and they may also represent interesting therapeutic
      tools for different types of peripheral neuropathy.

PMID- 22654838
TI  - The neurosteroid allopregnanolone modulates specific functions in central and
      peripheral glial cells.
AB  - Since the first observations on the existence of "neurosteroids" in the 1980s,
      our understanding of the importance of these endogenous steroids in the control
      of the central and peripheral nervous system (PNS) has increased progressively.
      Although most of the observations were made in neuronal cells, equally important
      are the effects that neurosteroids exert on glial cells. Among the different
      classes of neurosteroids acting on glial cells, the progesterone 5alpha-3alpha
      metabolite, allopregnanolone, displays a particular mechanism of action involving
      primarily the modulation of classic GABA receptors. In this review, we focus our
      attention on allopregnanolone because its effects on the physiology of glial
      cells of the central and PNS are intriguing and could potentially lead to the
      development of new strategies for neuroprotection and/or regeneration of injured
      nervous tissues.

PMID- 22654840
TI  - Prostaglandins and their receptors in insect biology.
AB  - We treat the biological significance of prostaglandins (PGs) and their known
      receptors in insect biology. PGs and related eicosanoids are oxygenated
      derivatives of arachidonic acid (AA) and two other C20 polyunsaturated fatty
      acids. PGs are mostly appreciated in the context of biomedicine, but a growing
      body of literature indicates the biological significance of these compounds
      extends throughout the animal kingdom, and possibly beyond. The actions of most
      PGs are mediated by specific receptors. Biomedical research has discovered a
      great deal of knowledge about PG receptors in mammals, including their
      structures, pharmacology, molecular biology and cellular locations. Studies of PG
      receptors in insects lag behind the biomedical background, however, recent
      results hold the promise of accelerated research in this area. A PG receptor has
      been identified in a class of lepidopteran hemocytes and experimentally linked to
      the release of prophenoloxidase. PGs act in several crucial areas of insect
      biology. In reproduction, a specific PG, PGE(2), releases oviposition behavior in
      most crickets and a few other insect species; PGs also mediate events in egg
      development in some species, which may represent all insects. PGs play major
      roles in modulating fluid secretion in Malpighian tubules, rectum and salivary
      glands, although, again, this has been studied in only a few insect species that
      may represent the Class. Insect immunity is a very complex defense system. PGs
      and other eicosanoids mediate a large number of immune reactions to infection and
      invasion. We conclude that research into PGs and their receptors in insects will
      lead to important advances in our understanding of insect biology.

PMID- 22654841
TI  - Rapid direct action of estradiol in GnRH neurons: findings and implications.
AB  - Estradiol plays a pivotal role in the control of gonadotropin-releasing hormone
      (GnRH) neuronal function and female reproduction. While positive and negative
      feedback actions of estradiol that enhance and suppress release of GnRH and LH
      are primarily mediated through estrogen receptor alpha located in interneurons, a
      series of recent studies in our laboratory indicate that rapid excitatory actions
      of estradiol also directly modify GnRH neuronal activity. We observed this
      phenomenon in cultured primate GnRH neurons, but similar rapid direct actions of
      estradiol are also described in cultured GnRH neurons and green fluorescent
      protein-labeled GnRH neurons of mice. Importantly, rapid direct action of
      estradiol in GnRH neurons is mediated through membrane or membrane associated
      receptors, such as GPR30, STX-sensitive receptors, and ERbeta. In this review,
      possible implications of this rapid estradiol action in GnRH neurons are
      discussed.

PMID- 22654842
TI  - Neuroendocrine pathways mediating nutritional acceleration of puberty: insights
      from ruminant models.
AB  - The pubertal process is characterized by an activation of physiological events
      within the hypothalamic-adenohypophyseal-gonadal axis which culminate in
      reproductive competence. Excessive weight gain and adiposity during the juvenile
      period is associated with accelerated onset of puberty in females. The mechanisms
      and pathways by which excess energy balance advances puberty are unclear, but
      appear to involve an early escape from estradiol negative feedback and early
      initiation of high-frequency episodic gonadotropin-releasing hormone (GnRH)
      secretion. Hypothalamic neurons, particularly neuropeptide Y and
      proopiomelanocortin neurons are likely important components of the pathway
      sensing and transmitting metabolic information to the control of GnRH secretion.
      Kisspeptin neurons may also have a role as effector neurons integrating metabolic
      and gonadal steroid feedback effects on GnRH secretion at the time of puberty.
      Recent studies indicate that leptin-responsive neurons within the ventral
      premammillary nucleus play a critical role in pubertal progression and challenge
      the relevance of kisspeptin neurons in this process. Nevertheless, the
      nutritional control of puberty is likely to involve an integration of major
      sensor and effector pathways that interact with modulatory circuitries for a fine
      control of GnRH neuron function. In this review, observations made in ruminant
      species are emphasized for a comparative perspective.

PMID- 22654843
TI  - PI3K: An Attractive Candidate for the Central Integration of Metabolism and
      Reproduction.
AB  - In neurons, as in a variety of other cell types, the enzyme phosphatidylinositol
      3-kinase (PI3K) is a key intermediate that is common to the signaling pathways of
      a number of peripheral metabolic cues, including insulin and leptin, which are
      well known to regulate both metabolic and reproductive functions. This review
      article will explore the possibility that PI3K is a key integrator of metabolic
      and neural signals regulating gonadotropin releasing hormone (GnRH)/luteinizing
      hormone (LH) release and explore the hypothesis that this enzyme is pivotal in
      many disorders where gonadotropin release is at risk. Although the mechanisms
      mediating the influence of metabolism and nutrition on fertility are currently
      unclear, the strong association between metabolic disorders and infertility is
      undeniable. For example, women suffering from anorectic disorders experience
      amenorrhea as a consequence of malnutrition-induced impairment of LH release, and
      at the other extreme, obesity is also commonly co-morbid with menstrual
      dysfunction and infertility. Impaired hypothalamic insulin and leptin receptor
      signaling is thought to be at the core of reproductive disorders associated with
      metabolic dysfunction. While low levels of leptin and insulin characterize states
      of negative energy balance, prolonged nutrient excess is associated with insulin
      and leptin resistance. Metabolic models known to alter GnRH/LH release such as
      diabetes, diet-induced obesity, and caloric restriction are also accompanied by
      impairment of PI3K signaling in insulin and leptin sensitive tissues including
      the hypothalamus. However, a clear link between this signaling pathway and the
      control of GnRH release by peripheral metabolic cues has not been established.
      Investigating the role of the signaling pathways shared by metabolic cues that
      are critical for a normal reproductive state can help identify possible targets
      in the treatment of metabolic and reproductive disorders such as polycystic
      ovarian syndrome.

PMID- 22654845
TI  - Wolbachia as an "infectious" extrinsic factor manipulating host signaling
      pathways.
AB  - Wolbachia pipientis is a widespread endosymbiont of filarial nematodes and
      arthropods. While in worms the symbiosis is obligate, in arthropods Wolbachia
      induces several reproductive manipulations (i.e., cytoplasmic incompatibility,
      parthenogenesis, feminization of genetic males, and male-killing) in order to
      increase the number of infected females. These various phenotypic effects may be
      linked to differences in host physiology, and in particular to endocrine-related
      processes governing growth, development, and reproduction. Indeed, a number of
      evidences links Wolbachia symbiosis to insulin and ecdysteroid signaling, two
      multilayered pathways known to work antagonistically, jointly or even
      independently for the regulation of different molecular networks. At present it
      is not clear whether Wolbachia manipulates one pathway, thus affecting other
      related metabolic networks, or if it targets both pathways, even interacting at
      several points in each of them. Interestingly, in view of the interplay between
      hormone signaling and epigenetic machinery, a direct influence of the "infection"
      on hormonal signaling involving ecdysteroids might be achievable through the
      manipulation of the host's epigenetic pathways.

PMID- 22654846
TI  - Transformation of a microprolactinoma into a mixed growth hormone and prolactin
      secreting pituitary adenoma.
AB  - Combined prolactin (PRL) and growth hormone (GH) secretion by a single pituitary
      tumor can occur in approximately 5% of cases. However, in all previously reported
      patients, combined secretion of both hormones was present at the time of
      diagnosis. Here we describe a patient initially diagnosed with a pure prolactin
      secreting microadenoma, who experienced the progressive apparition of symptomatic
      autonomous GH secretion while on intermittent long term dopamine agonist therapy.
      She was operated on, and immunohistochemical analysis of tumor tissue confirmed
      the diagnosis of pituitary adenoma with uniform co-staining of all cells for both
      GH and PRL. This patient represents the first documented occurrence of
      asynchronous development of combined GH and PRL secretion in a pituitary adenoma.
      Although pathogenic mechanisms implicated remain largely speculative, it
      emphasizes the need for long term hormonal follow up of patients harboring
      prolactinomas.

PMID- 22654844
TI  - Genetic regulation of the growth plate.
AB  - The epiphyseal growth plate consists of a layer of cartilage present only during
      the growth period and vanishes soon after puberty in long bones. It is divided to
      three well-defined zones, from epiphyses; resting, proliferative, and
      hypertrophic zones. Chondrocyte proliferation and differentiation and subsequent
      bone formation in this cartilage are controlled by various endocrine, autocrine,
      and paracrine factors which finally results into elimination of the cartilaginous
      tissue and promotion of the epiphyseal fusion. As chondrocytes differentiate from
      round, quiescent, and single structure to flatten and proliferative and then
      large and terminally differentiated, they experience changes in their gene
      expression pattern which allow them to transform from cartilaginous tissue to
      bone. This review summarizes the literature in this area and shortly describes
      different factors that affect growth plate cartilage both at the local and
      systemic levels. This may eventually help us to develop new treatment strategies
      of different growth disorders.

PMID- 22654847
TI  - Neuroregenerative mechanisms of allopregnanolone in Alzheimer's disease.
AB  - The proliferative pool and regenerative potential of neural stem cells diminishes
      with age, a phenomenon that may be exacerbated in prodromal and mild Alzheimer's
      disease (AD) brains. In parallel, the neuroactive progesterone metabolite,
      allopregnanolone (APalpha), along with a host of other factors, is decreased in
      the AD brain. Results of preclinical analyses demonstrate that APalpha is a
      potent inducer of neural progenitor proliferation of both rodent and human
      derived neural progenitor cells in vitro. In vivo, APalpha significantly
      increased neurogenesis within the subgranular zone of the dentate gyrus and
      subventricular zone of the 3xTgAD mouse model. Functionally, APalpha reversed the
      learning and memory deficits of 3xTgAD mice prior to and following the onset of
      AD pathology and was comparably efficacious in aged normal mice. In addition to
      inducing regenerative responses in mouse models of AD, APalpha significantly
      reduced beta-amyloid burden, beta-amyloid binding alcohol dehydrogenase load, and
      microglial activation. In parallel, APalpha increased markers of white matter
      generation and cholesterol homeostasis. Analyses to determine the optimal
      treatment regimen in the 3xTgAD mouse brain indicated that a treatment regimen of
      APalpha once per week was optimal for both inducing neurogenesis and reducing AD
      pathology. Pharmacokinetic analyses indicated that APalpha is rapidly increased
      in both plasma and brain following a single dose. APalpha is most efficacious
      when administered once per week which will contribute to its margin of safety.
      Further, analyses in both animals and humans have provided parameters for safe
      APalpha dosage exposure in humans. From a translational perspective, APalpha is a
      small molecular weight, blood brain barrier penetrant molecule with substantial
      preclinical efficacy data as a potential Alzheimer's therapeutic with existing
      safety data in animals and humans. To our knowledge, APalpha is the only small
      molecule that both promotes neural progenitor regeneration in brain and
      simultaneously reduces AD pathology burden.

PMID- 22654848
TI  - Mouse models of follicular and papillary thyroid cancer progression.
AB  - A significant number of well-differentiated thyroid cancers progress or recur,
      becoming resistant to current therapeutic options. Mouse models recapitulating
      the genetic and histological features of advanced thyroid cancer have been an
      invaluable tool to dissect the mechanisms involved in the progression from
      indolent, well differentiated tumors to aggressive, poorly differentiated
      carcinomas, and to identify novel therapeutic targets. In this review, we focus
      on the lessons learned from models of epithelial cell-derived thyroid cancer
      showing progression from hyperplastic lesions to locally invasive and metastatic
      carcinomas.

PMID- 22654850
TI  - Re-Evaluation of the PBAN Receptor Molecule: Characterization of PBANR Variants
      Expressed in the Pheromone Glands of Moths.
AB  - Sex pheromone production in most moths is initiated following pheromone
      biosynthesis activating neuropeptide receptor (PBANR) activation. PBANR was
      initially cloned from pheromone glands (PGs) of Helicoverpa zea and Bombyx mori.
      The B. mori PBANR is characterized by a relatively long C-terminus that is
      essential for ligand-induced internalization, whereas the H. zea PBANR has a
      shorter C-terminus that lacks features present in the B. mori PBANR critical for
      internalization. Multiple PBANRs have been reported to be concurrently expressed
      in the larval CNS of Heliothis virescens. In the current study, we sought to
      examine the prevalence of multiple PBANRs in the PGs of three moths and to
      ascertain their potential functional relevance. Multiple PBANR variants (As, A,
      B, and C) were cloned from the PGs of all species examined with PBANR-C the most
      highly expressed. Alternative splicing of the C-terminal coding sequence of the
      PBAN gene gives rise to the variants, which are distinguishable only by the
      length and composition of their respective C-terminal tails. Transient expression
      of fluorescent PBANR chimeras in insect cells revealed that PBANR-B and PBANR-C
      localized exclusively to the cell surface while PBANR-As and PBANR-A exhibited
      varying degrees of cytosolic localization. Similarly, only the PBANR-B and PBANR
      C variants underwent ligand-induced internalization. Taken together, our results
      suggest that PBANR-C is the principal receptor molecule involved in PBAN
      signaling regardless of moth species. The high GC content of the C-terminal
      coding sequence in the B and C variants, which makes amplification using
      conventional polymerases difficult, likely accounts for previous "preferential"
      amplification of PBANR-A like receptors from other species.

PMID- 22654851
TI  - New Insights toward the Acute Non-Thyroidal Illness Syndrome.
AB  - The non-thyroidal illness syndrome (NTIS) refers to changes in serum thyroid
      hormone levels observed in critically ill patients in the absence of hypothalamic
      pituitary-thyroid primary dysfunction. Affected individuals have low T3, elevated
      rT3, and inappropriately normal TSH levels. The pathophysiological mechanisms are
      poorly understood but the acute and chronic changes in pituitary-thyroid function
      are probably the consequence of the action of multiple factors. The early phase
      seems to reflect changes occurring primarily in the peripheral thyroid hormone
      metabolism, best seen in humans since 80-90% of the circulating T3 are derived
      from the pro-hormone T4. The conversion of T4 to T3 is catalyzed by type 1 (D1)
      and type 2 (D2) deiodinases via outer-ring deiodination. In contrast, type 3
      deiodinase (D3) catalyzes the inactivation of both T4 and T3. Over the last
      decades, several studies have attempted to elucidate the mechanisms underlying
      the changes on circulating thyroid hormones in NTIS. Increased inflammatory
      cytokines, which occurs in response to virtually any illness, has long been
      speculated to play a role in derangements of deiodinase expression. On the other
      hand, oxidative stress due to augmented reactive oxygen species (ROS) generation
      is characteristic of many diseases that are associated with NTIS. Changes in the
      intracellular redox state may disrupt deiodinase function by independent
      mechanisms, which might include depletion of the as yet unidentified endogenous
      thiol cofactor. Here we aim to present an updated picture of the advances in
      understanding the mechanisms that result in the fall of thyroid hormone levels in
      the acute phase of NTIS.

PMID- 22654849
TI  - Regulation of neurosteroid biosynthesis by neurotransmitters and neuropeptides.
AB  - The enzymatic pathways leading to the synthesis of bioactive steroids in the
      brain are now almost completely elucidated in various groups of vertebrates and,
      during the last decade, the neuronal mechanisms involved in the regulation of
      neurosteroid production have received increasing attention. This report reviews
      the current knowledge concerning the effects of neurotransmitters, peptide
      hormones, and neuropeptides on the biosynthesis of neurosteroids. Anatomical
      studies have been carried out to visualize the neurotransmitter- or neuropeptide
      containing fibers contacting steroid-synthesizing neurons as well as the
      neurotransmitter, peptide hormones, or neuropeptide receptors expressed in these
      neurons. Biochemical experiments have been conducted to investigate the effects
      of neurotransmitters, peptide hormones, or neuropeptides on neurosteroid
      biosynthesis, and to characterize the type of receptors involved. Thus, it has
      been found that glutamate, acting through kainate and/or AMPA receptors, rapidly
      inactivates P450arom, and that melatonin produced by the pineal gland and eye
      inhibits the biosynthesis of 7alpha-hydroxypregnenolone (7alpha-OH-Delta(5)P),
      while prolactin produced by the adenohypophysis enhances the formation of 7alpha
      OH-Delta(5)P. It has also been demonstrated that the biosynthesis of
      neurosteroids is inhibited by GABA, acting through GABA(A) receptors, and
      neuropeptide Y, acting through Y1 receptors. In contrast, it has been shown that
      the octadecaneuropetide ODN, acting through central-type benzodiazepine
      receptors, the triakontatetraneuropeptide TTN, acting though peripheral-type
      benzodiazepine receptors, and vasotocin, acting through V1a-like receptors,
      stimulate the production of neurosteroids. Since neurosteroids are implicated in
      the control of various neurophysiological and behavioral processes, these data
      suggest that some of the neurophysiological effects exerted by neurotransmitters
      and neuropeptides may be mediated via the regulation of neurosteroid production.

PMID- 22654853
TI  - The structural determinants of insulin-like Peptide 3 activity.
AB  - Insulin-like peptide 3 (INSL3) is a hormone and/or paracrine factor which is a
      member of the relaxin peptide family. It has key roles as a fertility regulator
      in both males and females. The receptor for INSL3 is the leucine rich repeat
      (LRR) containing G-protein coupled receptor 8 (LGR8) which is now known as
      relaxin family peptide receptor 2 (RXFP2). Receptor activation by INSL3 involves
      binding to the LRRs in the large ectodomain of RXFP2 by residues within the B
      chain of INSL3 as well as an interaction with the transmembrane exoloops of the
      receptor. Although the binding to the LRRs is well characterized the features of
      the peptide and receptor involved in the exoloop interaction are currently
      unknown. This study was designed to determine the key INSL3 determinants for
      RXFP2 activation. A chimeric peptide approach was first utilized to demonstrate
      that the A-chain is critical for receptor activation. Replacement of the INSL3 A
      chain with that from the related peptides INSL5 and INSL6 resulted in complete
      loss of activity despite only minor changes in binding affinity. Subsequent
      replacement of specific A-chain residues with those from the INSL5 peptide
      highlighted that the N-terminus of the A-chain of INSL3 is critical for its
      activity. Remarkably, replacement of the entire N-terminus with four or five
      alanine residues resulted in peptides with near native activity suggesting that
      specific residues are not necessary for activity. Additionally removal of two
      amino acids at the C-terminus of the A-chain and mutation of Lys-8 in the B-chain
      also resulted in minor decreases in peptide activity. Therefore we have
      demonstrated that the activity of the INSL3 peptide is driven predominantly by
      residues 5-9 in the A-chain, with minor additional contributions from the two C
      terminal A-chain residues and Lys-8 in the B-chain. Using this new knowledge, we
      were able to produce a truncated INSL3 peptide structure which retained native
      activity, despite having 14 fewer residues than the parent peptide.

PMID- 22654852
TI  - Neurosteroid influences on sensitivity to ethanol.
AB  - This review will highlight a variety of mechanisms by which neurosteroids affect
      sensitivity to ethanol, including physiological states associated with activity
      of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal
      (HPG) axes, and the effects of chronic exposure to ethanol, in addition to
      behavioral implications. To date, gamma-aminobutyric acid (GABA(A)) receptor
      mechanisms are a major focus of the modulation of ethanol effects by neuroactive
      steroids. While NMDA receptor mechanisms are gaining prominence in the
      literature, these complex data would be best discussed separately. Accordingly,
      GABA(A) receptor mechanisms are emphasized in this review with brief mention of
      some NMDA receptor mechanisms to point out contrasting neuroactive steroid
      pharmacology. Overall, the data suggest that neurosteroids are virtually
      ubiquitous modulators of inhibitory neurotransmission. Neurosteroids appear to
      affect sensitivity to ethanol in specific brain regions and, consequently,
      specific behavioral tests, possibly related to the efficacy and potency of
      ethanol to potentiate the release of GABA and increase neurosteroid
      concentrations. Although direct interaction of ethanol and neuroactive steroids
      at common receptor binding sites has been suggested in some studies, this
      proposition is still controversial. It is currently difficult to assign a
      specific mechanism by which neuroactive steroids could modulate the effects of
      ethanol in particular behavioral tasks.

PMID- 22654854
TI  - Recruitment of brown adipose tissue as a therapy for obesity-associated diseases.
AB  - Brown adipose tissue (BAT) has been recognized for more than 20 years to play a
      key role in cold-induced non-shivering thermogenesis (CIT, NST), and body weight
      homeostasis in animals. BAT is a flexible tissue that can be recruited by stimuli
      (including small molecules in animals), and atrophies in the absence of a
      stimulus. In fact, the contribution of BAT (and UCP1) to resting metabolic rate
      and healthy body weight homeostasis in animals (rodents) is now well established.
      Many investigations have shown that resistance to obesity and associated
      disorders in various rodent models is due to increased BAT mass and the number of
      brown adipocytes or UCP1 expression in various depots. The recent discovery of
      active BAT in adult humans has rekindled the notion that BAT is a therapeutic
      target for combating obesity-related metabolic disorders. In this review, we
      highlight investigations performed in rodents that support the contention that
      activation of BAT formation and/or function in obese individuals is
      therapeutically powerful. We also propose that enhancement of brown adipocyte
      functions in white adipose tissue (WAT) will also regulate energy balance as well
      as reduce insulin resistance in obesity-associated inflammation in WAT.

PMID- 22654855
TI  - Congenital Hypothyroidism with Gland in situ is More Frequent than Previously
      Thought.

PMID- 22654857
TI  - Intracerebroventricular infusion of vasoactive intestinal Peptide rescues the
      luteinizing hormone surge in middle-aged female rats.
AB  - Reproductive aging is characterized by delayed and attenuated luteinizing hormone
      (LH) surges apparent in middle-aged rats. The suprachiasmatic nucleus (SCN)
      contains the circadian clock that is responsible for the timing of diverse
      neuroendocrine rhythms. Electrophysiological studies suggest vasoactive
      intestinal peptide (VIP) originating from the SCN excites gonadotropin-releasing
      hormone (GnRH) neurons and affects daily patterns of GnRH-LH release. Age-related
      LH surge dysfunction correlates with reduced VIP mRNA expression in the SCN and
      fewer GnRH neurons with VIP contacts expressing c-fos, a marker of neuronal
      activation, on the day of the LH surge. To determine if age-related LH surge
      dysfunction reflects reduced VIP availability or altered VIP responsiveness under
      estradiol positive feedback conditions, we assessed the effect of
      intracerebroventricular (icv) VIP infusion on c-fos expression in GnRH neurons
      and on LH release in ovariohysterectomized, hormone-primed young and middle-aged
      rats. Icv infusion of VIP between 1300 and 1600 h significantly advanced the time
      of peak LH release, increased total and peak LH release, and increased the number
      of GnRH neurons expressing c-fos on the day of the LH surge in middle-aged rats.
      Surprisingly, icv infusion of VIP in young females significantly reduced the
      number of GnRH neurons expressing c-fos and delayed and reduced the LH surge.
      These observations suggest that a critical balance of VIP signaling is required
      to activate GnRH neurons for an appropriately timed and robust LH surge in young
      and middle-aged females. Age-related LH surge changes may, in part, result from
      decreased availability and reduced VIP-mediated neurotransmission under estradiol
      positive feedback conditions.

PMID- 22654858
TI  - Outcome of endoscopy-assisted microscopic extended transsphenoidal surgery for
      suprasellar adult craniopharyngiomas.
AB  - Craniopharyngiomas are difficult to treat. The extended transsphenoidal approach
      has recently been described in several small series. We describe the usefulness
      of microscopy-assisted angled endoscopy for visualizing vital structures such as
      tumor attachment or tumor invasion to the pituitary stalk to achieve confident
      radical tumor removal. Between 2006 and 2010, 15 patients underwent the
      microscopy-assisted extended transsphenoidal approach for resection of entirely
      suprasellar craniopharyngiomas. Fourteen patients had the transinfundibular type,
      and one had the transinfundibular type with extension to the third ventricle. We
      observed color change within the pituitary stalk by endoscopy. The pituitary
      stalk was cut intentionally in 10 patients because of suspected tumor invasion
      surrounding the stalk. Total removal was accomplished in nine patients.
      Pathological specimens from the pituitary stalk showed tumor invasion spreading
      over the surface of the pituitary stalk, shown by a discolored pituitary stalk,
      and this was essential for confident radical tumor removal. Even after stalk
      resection, postoperative diabetes insipidus was minimal when a bright signal on
      T1 in the posterior lobe was not observed with preoperative magnetic resonance
      imaging. Confident radical tumor removal is possible with the introduction of the
      endoscopy-assisted microscopic extended transsphenoidal approach.

PMID- 22654856
TI  - Tissue-Specific Effects of Loss of Estrogen during Menopause and Aging.
AB  - The roles of estrogens have been best studied in the breast, breast cancers, and
      in the female reproductive tract. However, estrogens have important functions in
      almost every tissue in the body. Recent clinical trials such as the Women's
      Health Initiative have highlighted both the importance of estrogens and how
      little we know about the molecular mechanism of estrogens in these other tissues.
      In this review, we illustrate the diverse functions of estrogens in the bone,
      adipose tissue, skin, hair, brain, skeletal muscle and cardiovascular system, and
      how the loss of estrogens during aging affects these tissues. Early
      transcriptional targets of estrogen are reviewed in each tissue. We also describe
      the tissue-specific effects of selective estrogen receptor modulators (SERMs)
      used for the treatment of breast cancers and postmenopausal symptoms.

PMID- 22654859
TI  - Evolutionary Insights into the Steroid Sensitive kiss1 and kiss2 Neurons in the
      Vertebrate Brain.
AB  - Kisspeptin was originally found as a peptide product of Kiss1 gene and is now
      supposed to be an essential central regulator of reproduction in mammals.
      However, there is now a growing body of evidence to suggest that kiss2, the
      paralogous gene for kiss1, evolved in parallel during vertebrate lineage, and the
      kiss2 product also activates the GPR54 (kisspeptin receptor) signaling pathways.
      Therefore, it is now widely accepted that both kiss1 and kiss2 are the kisspeptin
      genes. Interestingly, either kiss1 or kiss2 or both have been lost during
      evolution in many vertebrate species, and the functional significance of kiss1 or
      kiss2 for the central regulation of reproduction is suggested to vary according
      to the species. Here, we argue that the steroid sensitivity of the kiss1 or kiss2
      neurons has been well conserved during evolution among tetrapods and teleosts,
      and thus it may be the key to understanding the functional homologies of certain
      populations of kisspeptin (kiss1 or kiss2) neurons among different species of
      vertebrates. In the present review, we will first introduce recent advances in
      the study of steroid sensitive kiss1 and kiss2 systems in vertebrates and effects
      of peptide administrations in vivo. By comparing the similarities and differences
      between kiss1 and kiss2 of neuronal localization and sensitivity to gonadal
      steroids in various tetrapods and teleosts, we discuss the evolution of
      kisspeptin neuronal systems after gene duplication of ancestral kisspeptin genes
      to give rise to kiss1 and kiss2.

PMID- 22654860
TI  - Molecular Structure and Diversity of PBAN/pyrokinin Family Peptides in Ants.
AB  - Neuropeptides are the largest group of insect hormones. They are produced in the
      central and peripheral nervous systems and affect insect development,
      reproduction, feeding, and behavior. A variety of neuropeptide families have been
      identified in insects. One of these families is the PBAN/pyrokinin family defined
      by a common FXPRLamide or similar amino acid fragment at the C-terminal end.
      These peptides, found in all insects studied thus far, have been conserved
      throughout evolution. The most well studied physiological function is regulation
      of moth sex pheromone biosynthesis through the pheromone biosynthesis activating
      neuropeptide (PBAN), although several developmental functions have also been
      reported. Over the past years we have extended knowledge of the PBAN/pyrokinin
      family of peptides to ants, focusing mainly on the fire ant, Solenopsis invicta.
      The fire ant is one of the most studied social insects and over the last 60 years
      a great deal has been learned about many aspects of this ant, including the
      behaviors and chemistry of pheromone communication. However, virtually nothing is
      known about the regulation of these pheromone systems. Recently, we demonstrated
      the presence of PBAN/pyrokinin immunoreactive neurons in the fire ant, and
      identified and characterized PBAN and additional neuropeptides. We have mapped
      the fire ant PBAN gene structure and determined the tissue expression level in
      the central nervous system of the ant. We review here our research to date on the
      molecular structure and diversity of ant PBAN/pyrokinin peptides in preparation
      for determining the function of the neuropeptides in ants and other social
      insects.

PMID- 22654861
TI  - TGF-beta/Smad3 Signaling Regulates Brown Adipocyte Induction in White Adipose
      Tissue.
AB  - Recent identification of active brown fat reserves in adult humans has re
      stimulated interest in the role of brown adipocytes in energy homeostasis. In
      addition, there is accumulating evidence to support the concept of an alteration
      in energy balance through acquisition of brown fat features in traditional white
      fat depots. We recently described an important role played by the TGF-beta/Smad3
      signaling pathway in modulating the appearance of brown adipocytes in traditional
      white fat, and its implications to thermogenesis, mitochondrial energetics,
      energy expenditure, and protection from diabetes and obesity. Here we review the
      data supporting this phenomenon and put into perspective the promise of
      conversion of white fat to a brown fat state as a potential therapeutic option
      for obesity and diabetes.

PMID- 22654862
TI  - Control and physiological determinants of sympathetically mediated brown adipose
      tissue thermogenesis.
AB  - Brown adipose tissue (BAT) represents a remarkable heat-producing tissue. The
      thermogenic potential of BAT is conferred by uncoupling protein 1, a protein
      found uniquely in brown adipocytes. BAT activity and capacity is controlled by
      the sympathetic nervous system (SNS), which densely innervates brown fat depots.
      SNS-mediated BAT thermogenesis is essentially governed by hypothalamic and
      brainstem neurons. BAT activity is also modulated by brain energy balance
      pathways including the very significant brain melanocortin system, suggesting a
      genuine involvement of SNS-mediated BAT thermogenesis in energy homeostasis. The
      use of positron emission tomography/computed tomography scanning has revealed the
      presence of well-defined BAT depots in the cervical, clavicular, and paraspinal
      areas in adult humans. The prevalence of these depots is higher in subjects
      exposed to low temperature and is also higher in women compared to men. Moreover,
      the prevalence of BAT decreases with age and body fat mass, suggesting that BAT
      could be involved in energy balance regulation and obesity in humans. This short
      review summarizes recent progress made in our understanding of the control of SNS
      mediated BAT thermogenesis and of the determinants of BAT prevalence or detection
      in humans.

PMID- 22654863
TI  - Insulin-like growth factor binding proteins: a structural perspective.
AB  - Insulin-like growth factor binding proteins (IGFBP-1 to -6) bind insulin-like
      growth factors-I and -II (IGF-I and IGF-II) with high affinity. These binding
      proteins maintain IGFs in the circulation and direct them to target tissues,
      where they promote cell growth, proliferation, differentiation, and survival via
      the type 1 IGF receptor. IGFBPs also interact with many other molecules, which
      not only influence their modulation of IGF action but also mediate IGF
      independent activities that regulate processes such as cell migration and
      apoptosis by modulating gene transcription. IGFBPs-1 to -6 are structurally
      similar proteins consisting of three distinct domains, N-terminal, linker, and C
      terminal. There have been major advances in our understanding of IGFBP structure
      in the last decade and a half. While there is still no structure of an intact
      IGFBP, several structures of individual N- and C-domains have been solved. The
      structure of a complex of N-BP-4:IGF-I:C-BP-4 has also been solved, providing a
      detailed picture of the structural features of the IGF binding site and the
      mechanism of binding. Structural studies have also identified features important
      for interaction with extracellular matrix components and integrins. This review
      summarizes structural studies reported so far and highlights features important
      for binding not only IGF but also other partners. We also highlight future
      directions in which structural studies will add to our knowledge of the role
      played by the IGFBP family in normal growth and development, as well as in
      disease.

PMID- 22654864
TI  - Intracystic therapies for cystic craniopharyngioma in childhood.
AB  - INTRODUCTION: Craniopharyngioma of childhood are commonly cystic in nature. An
      intracystic catheter insertion and subsequent instillation of substances inducing
      cyst shrinkage seems a beneficial strategy avoiding additional morbidity in a
      highly vulnerable brain location. METHODS: A systematic review of the medical
      literature was performed to identify potentially relevant, all languages articles
      using Ovid MEDLINE and EMBASE from inception to July 2011 and Cochrane Central
      Register of Controlled Trials to third quarter 2011. All references were examined
      for relevancy. RESULTS: Of 142 unique references, 71 referred to substances used
      for intracystic craniopharyngioma treatment. General aspects of intracystic
      catheter insertion as well as response rates, risks, and outcomes of children
      treated with intracystic radioisotopes, bleomycin, and interferon (IFN) are
      critically reviewed and an outline for potential future endeavors provided.
      CONCLUSION: IFN seems currently the intracystic substance with the best benefit
      risk ratio. The authors advocate for consensus on prospective data collection and
      standardized intracystic treatment strategies to allow reliable comparisons and
      herewith optimize treatment and outcome.

PMID- 22654865
TI  - The P2X7 Receptor is an Important Regulator of Extracellular ATP Levels.
AB  - Controlled ATP release has been demonstrated from many neuronal and non-neuronal
      cell types. Once released, extracellular ATP acts on cells in a paracrine manner
      via purinergic receptors. Considerable evidence now suggests that extracellular
      nucleotides, signaling via P2 receptors, play important roles in bone homeostasis
      modulating both osteoblast and osteoclast function. In this study, we demonstrate
      that mouse osteoclasts and their precursors constitutively release ATP into their
      extracellular environment. Levels were highest at day 2 (precursor cells),
      possibly reflecting the high number of red blood cells and accessory cells
      present. Mature osteoclasts constitutively released ATP in the range 0.05-0.5
      pmol/ml/cell. Both osteoclasts and osteoblasts express mRNA and protein for the
      P2X7 receptor. We found that in osteoclasts, expression levels are fourfold
      higher in mature cells relative to precursors, whilst in osteoblasts expression
      remains relatively constant during differentiation. Selective antagonists (0.1
      100 MUM AZ10606120, A438079, and KN-62) were used to determine whether this
      release was mediated via P2X7 receptors. AZ10606120, A438079, and KN-62, at 0.1
      10 MUM, decreased ATP release by mature osteoclasts by up to 70, 60, and 80%,
      respectively. No differences in cell viability were observed. ATP release also
      occurs via vesicular exocytosis; inhibitors of this process (1-100 MUM NEM or
      brefeldin A) had no effect on ATP release from osteoclasts. P2X7 receptor
      antagonists (0.1-10 MUM) also decreased ATP release from primary rat osteoblasts
      by up to 80%. These data show that ATP release via the P2X7 receptor contributes
      to extracellular ATP levels in osteoclast and osteoblast cultures, suggesting an
      important additional role for this receptor in autocrine/paracrine purinergic
      signaling in bone.

PMID- 22654866
TI  - The Arginine Residue within the C-Terminal Active Core of Bombyx mori Pheromone
      Biosynthesis-Activating Neuropeptide is Essential for Receptor Binding and
      Activation.
AB  - In most lepidopteran insects, the biosynthesis of sex pheromones is regulated by
      pheromone biosynthesis-activating neuropeptide (PBAN). Bombyx mori PBAN (BomPBAN)
      consists of 33 amino acid residues and contains a C-terminus FSPRLamide motif as
      the active core. Among neuropeptides containing the FXPRLamide motif, the
      arginine (Arg, R) residue at the second position from the C-terminus is highly
      conserved across several neuropeptides, which can be designated as RXamide
      peptides. The purpose of this study was to clarify the role of the Arg residue in
      the BomPBAN active core. We synthesized 10-residue peptides corresponding to the
      C-terminal part of BomPBAN with a series of replacements at the second position
      from the C-terminus, termed the C2 position, and measured their efficacy in
      stimulating Ca(2+) influx in insect cells expressing a fluorescent PBAN receptor
      chimera (PBANR-EGFP) using the fluorescent Ca(2+) indicator, Fura Red-AM. The
      PBAN analogs with the C2 position replaced with alanine (Ala, A), aspartic acid
      (Asp, D), serine (Ser, S), or l-2-aminooctanoic acid (Aoc) decreased PBAN-like
      activity. R(C2)A (SKTRYFSPALamide) and R(C2)D (SKTRYFSPDLamide) had the lowest
      activity and could not inhibit the activity of PBAN C10 (SKTRYFSPRLamide). We
      also prepared Rhodamine Red-labeled peptides of the PBAN analogs and examined
      their ability to bind PBANR. In contrast to Rhodamine Red-PBAN C10 at 100 nM,
      none of the synthetic analogs exhibited PBANR binding at the same concentration.
      Taken together, our results demonstrate that the C2 Arg residue in BomPBAN is
      essential for PBANR binding and activation.

PMID- 22654867
TI  - Cytoplasmic travels of the ecdysteroid receptor in target cells: pathways for
      both genomic and non-genomic actions.
AB  - Signal transduction of the insect steroid hormones, ecdysteroids, is mediated by
      the ecdysteroid receptor, EcR. In various cells of the insect Rhodnius prolixus,
      EcR is present in both the nucleus and the cytoplasm, where it undergoes daily
      cycling in abundance and cellular location at particular developmental times of
      the last larval instar that are specific to different cell types. EcR favors a
      cytoplasmic location in the day and a nuclear location in the night. This study
      is the first to examine the potential mechanisms of intracellular transport of
      EcR and reveals close similarities with some of its mammalian counterparts. In
      double and triple labels using several antibodies, immunohistochemistry, and
      confocal laser scanning microscopy, we observed co-localization of EcR with the
      microtubules (MTs). Treatments with either the MT-stabilizing agent taxol or with
      colchicine, which depolymerizes MTs, resulted in considerable reduction in
      nuclear EcR with a concomitant increase in cytoplasmic EcR suggesting that MT
      disruption inhibits receptor accumulation in the nucleus. EcR also co-localizes
      with the chaperone Hsp90, the immunophilin FKBP52, and the light chain 1 of the
      motor protein dynein. All these factors also co-localize with MTs. We propose
      that in Rhodnius, EcR exerts its genomic effects by forming a complex with Hsp90
      and FKBP52, which uses dynein on MTs as a mechanism for daily nucleocytoplasmic
      shuttling. The complex is transported intact to the nucleus and dissociates
      within it. We propose that EcR utilizes the cytoskeletal tracks for movement in a
      manner closely similar to that used by the glucocorticoid receptor. We also
      observed co-localization of EcR with mitochondria which suggests that EcR, like
      its mammalian counterparts, may be involved in the coordination of non-genomic
      responses of ecdysteroids in mitochondria.

PMID- 22654868
TI  - Craniopharyngioma in adults.
AB  - Craniopharyngiomas are slow growing benign tumors of the sellar and parasellar
      region with an overall incidence rate of approximately 1.3 per million. During
      adulthood there is a peak incidence between 40 and 44 years. There are two
      histopathological types, the adamantinomatous and the papillary type. The later
      type occurs almost exclusively in adult patients. The presenting symptoms develop
      over years and display a wide spectrum comprising visual, endocrine,
      hypothalamic, neurological, and neuropsychological manifestations. Currently, the
      main treatment option consists in surgical excision followed by radiation therapy
      in case of residual tumor. Whether gross total or partial resection should be
      preferred has to be balanced on an individual basis considering the extent of the
      tumor (e.g., hypothalamic invasion). Although the overall long-term survival is
      good it is often associated with substantial morbidity. Preexisting disorders are
      often permanent or even exacerbated by treatment. Endocrine disturbances need
      careful replacement and metabolic sequelae should be effectively treated. Regular
      follow-up by a multidisciplinary team is a prerequisite for optimal outcome of
      these patients.

PMID- 22654869
TI  - Integrating body and organ size in Drosophila: recent advances and outstanding
      problems.
AB  - OVER THE PAST TWO DECADES, FUNDAMENTAL STRIDES IN PHYSIOLOGY AND GENETICS HAVE
      ALLOWED US TO FINALLY GRASP THE DEVELOPMENTAL MECHANISMS REGULATING BODY SIZE,
      PRIMARILY IN ONE MODEL ORGANISM: the fruit fly Drosophila melanogaster. In
      Drosophila, as in all animals, final body size is regulated by the rate and
      duration of growth. These studies have identified important roles for the insulin
      and the target of rapamycin (TOR) signaling pathways in regulating the growth
      rate of the larva, the stage most important in determining final adult size.
      Furthermore, they have shown that the insulin/TOR pathway interacts with hormonal
      systems, like ecdysone and juvenile hormone, to regulate the timing of
      development and hence the duration of growth. This interaction allows the growing
      larvae to integrate cues from the environment with environmentally sensitive
      developmental windows to ensure that optimal size and proportions are reached
      given the larval rearing conditions. Results from this work have opened up new
      avenues of studies, including how environmental cues are integrated to regulate
      developmental time and how organs maintain proportional growth. Other researchers
      interested in the evolution of body size are beginning to apply these results to
      studies of body size evolution and the generation of allometry. With these new
      findings, and with the developments to come, the field of size control finds
      itself in the fortunate position of finally being able to tackle century old
      questions of how organisms achieve final adult size and proportions. This review
      discusses the state of the art of size control from a Drosophila perspective, and
      outlines an approach to resolving outstanding issues.

PMID- 22654871
TI  - Is the bench getting closer to the bedside in the war on cancer? A quick look at
      prostate cancer.

PMID- 22654870
TI  - Estrogenic regulation of the GnRH neuron.
AB  - Reproductive function is regulated by the secretion of luteinizing hormone (LH)
      and follicle-stimulating hormone from the pituitary and the steroid hormones from
      the gonads. The dynamic changes in the levels of the reproductive hormones
      regulate secondary sex characteristics, gametogenesis, cellular function, and
      behavior. Hypothalamic GnRH neurons, with cell bodies located in the basal
      hypothalamus, represent the final common pathway for neuronally derived signals
      to the pituitary. As such, they serve as integrators of a dizzying array of
      signals including sensory inputs mediating information about circadian, seasonal,
      behavioral, pheromonal, and emotional cues. Additionally, information about
      peripheral physiological function may also be included in the integrative signal
      to the GnRH neuron. These signals may communicate information about metabolic
      status, disease, or infection. Gonadal steroid hormones arguably exert the most
      important effects on GnRH neuronal function. In both males and females, the
      gonadal steroid hormones exert negative feedback regulation on axis activity at
      both the level of the pituitary and the hypothalamus. These negative feedback
      loops regulate homeostasis of steroid hormone levels. In females, a cyclic
      reversal of estrogen feedback produces a positive feedback loop at both the
      hypothalamic and pituitary levels. Central positive feedback results in a
      dramatic increase in GnRH secretion (Moenter et al., 1992; Xia et al., 1992;
      Clarke, 1993; Sisk et al., 2001). This is coupled with an increase in pituitary
      sensitivity to GnRH (Savoy-Moore et al., 1980; Turzillo et al., 1995), which
      produces the massive surge in secretion of LH that triggers ovulation. While
      feedback regulation of the axis in males is in part mediated by estrogen
      receptors (ER), there is not a clear consensus as to the relative role of ER
      versus AR signaling in males (Lindzey et al., 1998; Wersinger et al., 1999).
      Therefore, this review will focus on estrogenic signaling in the female.

PMID- 22654873
TI  - Metabolic Effects of Insulin and IGFs on Gilthead Sea Bream (Sparus aurata)
      Muscle Cells.
AB  - Primary cultures of gilthead sea bream myocytes were performed in order to
      examine the relative metabolic function of insulin compared with IGF-I and IGF-II
      (insulin-like growth factors, IGFs) at different stages in the cell culture. In
      these cells, the in vitro effects of insulin and IGFs on 2-deoxyglucose (2-DG)
      and l-alanine uptake were studied in both myocytes (day 4) and small myotubes
      (day 9). 2-DG uptake in gilthead sea bream muscle cells was increased in the
      presence of insulin and IGFs in a time dependent manner and along with muscle
      cell differentiation. On the contrary, l-alanine uptake was also stimulated by
      insulin and IGFs but showed an inverse pattern, being the uptake higher in small
      myocytes than in large myotubes. The results of preincubation with inhibitors (PD
      98059, wortmannin, and cytochalasin B) on 2-DG uptake indicated that insulin and
      IGFs stimulate glucose uptake through the same mechanisms, and evidenced that
      mitogenesis activator protein kinase (MAPK) and PI3K-Akt transduction pathways
      mediate the metabolic function of these peptides. In the same way, we observed
      that GLUT4 protein synthesis was stimulated in the presence of insulin and IGFs
      in gilthead sea bream muscle cells in a different manner at days 4 or 9 of the
      culture. In summary we describe here, for the first time, the effects of insulin
      and IGFs on 2-DG and l-alanine uptake in primary culture of gilthead sea bream
      muscle cells. We show that both MAPK and PI3K-Akt transduction pathways are
      needed in order to control insulin and IGFs actions in these cells. Moreover,
      changes in glucose uptake can be explained by the action of the GLUT4
      transporter, which is stimulated in the presence of insulin and IGFs throughout
      the cell culture.

PMID- 22654872
TI  - RET/PTC Translocations and Clinico-Pathological Features in Human Papillary
      Thyroid Carcinoma.
AB  - Thyroid carcinoma is the most frequent endocrine cancer accounting for 5-10% of
      thyroid nodules. Papillary histotype (PTC) is the most prevalent form accounting
      for 80% of all thyroid carcinoma. Although much is known about its epidemiology,
      pathogenesis, clinical, and biological behavior, the only documented risk factor
      for PTC is the ionizing radiation exposure. Rearrangements of the Rearranged
      during Transfection (RET) proto-oncogene are found in PTC and have been shown to
      play a pathogenic role. The first RET rearrangement, named RET/PTC, was
      discovered in 1987. This rearrangement constitutively activates the transcription
      of the RET tyrosine-kinase domain in follicular cell, thus triggering the
      signaling along the MAPK pathway and an uncontrolled proliferation. Up to now, 13
      different types of RET/PTC rearrangements have been reported but the two most
      common are RET/PTC1 and RET/PTC3. Ionizing radiations are responsible for the
      generation of RET/PTC rearrangements, as supported by in vitro studies and by the
      evidence that RET/PTC, and particularly RET/PTC3, are highly prevalent in
      radiation induced PTC. However, many thyroid tumors without any history of
      radiation exposure harbor similar RET rearrangements. The overall prevalence of
      RET/PTC rearrangements varies from 20 to 70% of PTCs and they are more frequent
      in childhood than in adulthood thyroid cancer. Controversial data have been
      reported on the relationship between RET/PTC rearrangements and the PTC
      prognosis. RET/PTC3 is usually associated with a more aggressive phenotype and in
      particular with a greater tumor size, the solid variant, and a more advanced
      stage at diagnosis which are all poor prognostic factors. In contrast, RET/PTC1
      rearrangement does not correlate with any clinical-pathological characteristics
      of PTC. Moreover, the RET protein and mRNA expression level did not show any
      correlation with the outcome of patients with PTC and no correlation between
      RET/PTC rearrangements and the expression level of the thyroid differentiation
      genes was observed. Recently, a diagnostic role of RET/PTC rearrangements has
      been proposed. It can be searched for in the mRNA extracted from cytological
      sample especially in case with indeterminate cytology. However, both the fact
      that it can be present in a not negligible percentage of benign cases and the
      technical challenge in extracting mRNA from cytological material makes this
      procedure not applicable at routine level, at least for the moment.

PMID- 22654874
TI  - Establishment of Sf9 Transformants Constitutively Expressing PBAN Receptor
      Variants: Application to Functional Evaluation.
AB  - To facilitate further evaluation of pheromone biosynthesis activating
      neuropeptide receptor (PBANR) functionality and regulation, we generated cultured
      insect cell lines constitutively expressing green fluorescent protein chimeras of
      the recently identified Bombyx mori PBANR (BommoPBANR) and Pseudaletia separata
      PBANR (PsesePBANR) variants. Fluorescent chimeras included the BommoPBANR-A, -B,
      and -C variants and the PsesePBANR-B and -C variants. Cell lines expressing non
      chimeric BommoPBANR-B and -C variants were also generated. Functional evaluation
      of these transformed cell lines using confocal laser microscopy revealed that a
      Rhodamine Red-labeled PBAN derivative (RR-C10PBAN(R2K)) specifically co-localized
      with all of the respective PBANR variants at the plasma membrane. Near complete
      internalization of the fluorescent RR-C10PBAN(R2K) ligand 30 min after binding
      was observed in all cell lines except those expressing the BommoPBANR-A variant,
      in which the ligand/receptor complex remained at the plasma membrane. Fluorescent
      Ca(2+) imaging further showed that the BommoPBANR-A cell line exhibited
      drastically different Ca(2+) mobilization kinetics at a number of RR-C10PBAN(R2K)
      concentrations including 10 MUM. These observations demonstrate a clear
      functional difference between the BommoPBANR-A variant and the BommoPBANR-B and 
      C variants in terms of receptor regulation and activation of downstream effector
      molecules. We also found that, contrary to previous reports, ligand-induced
      internalization of BommoPBANR-B and BommoPBANR-C in cell lines stably expressing
      these variants occurred in the absence of extracellular Ca(2+).

PMID- 22654875
TI  - Application of liquid-based cytology to fine-needle aspiration biopsies of the
      thyroid gland.
AB  - Fine-needle aspiration biopsy is regarded as an important tool for diagnosing
      thyroid lesions because of its simplicity, safety, and cost-effectiveness. Its
      role in correctly characterizing the group of indeterminate lesions or follicular
      patterned neoplasms (FN) might be more decisive. Liquid-based cytology (LBC) is a
      technique based on the use of a semi-automated device that has gained popularity
      as a method of collecting and processing both gynecologic and non-gynecologic
      cytologic specimens. It achieves a diagnostic sensitivity as accurate as
      conventional preparations especially for its excellent cell preservation and for
      the lack of background which decrease the amount of inadequate diagnoses.
      Moreover, the cellular material which has been stored in the preservative
      solution could be effectively used for the application of immunocytochemical and
      molecular techniques especially for the Follicular proliferations. In many cases
      the cytologic features are similar in both methods but the colloid film and the
      lymphocytic component are more easily evaluated on direct smears whereas nuclear
      details and colloid globules are better evaluated in LBC slides. The LBC
      processed biopsies represent a valid alternative to conventional cytology. The
      possibility of applying special techniques enhance the efficacy of the
      cytological diagnosis of thyroid lesions.

PMID- 22654876
TI  - Familial follicular cell-derived thyroid carcinoma.
AB  - Follicular cell-derived well-differentiated thyroid cancer, papillary (PTC) and
      follicular thyroid carcinomas comprise 95% of all thyroid malignancies. Familial
      follicular cell-derived well-differentiated thyroid cancers contribute 5% of
      cases. Such familial follicular cell-derived carcinomas or non-medullary thyroid
      carcinomas (NMTC) are divided into two clinical-pathological groups. The
      syndromic-associated group is composed of predominately non-thyroidal tumors and
      includes Pendred syndrome, Warner syndrome, Carney complex (CNC) type 1, PTEN
      hamartoma tumor syndrome (PHTS; Cowden disease), and familial adenomatous
      polyposis (FAP)/Gardner syndrome. Other conditions with less established links to
      the development of follicular cell-derived tumors include ataxia-telangiectasia
      syndrome, McCune Albright syndrome, and Peutz-Jeghers syndrome. The final group
      encompasses syndromes typified by NMTC, as well as pure familial (f) PTC with or
      without oxyphilia, fPTC with multinodular goiter, and fPTC with papillary renal
      cell carcinoma. This heterogeneous group of diseases does not have the
      established genotype-phenotype correlations known as in the familial C-cell
      derived tumors or medullary thyroid carcinomas (MTC). Clinicians should have the
      knowledge to identify the likelihood of a patient presenting with thyroid cancer
      having an additional underlying familial syndrome stemming from characteristics
      by examining morphological findings that would alert pathologists to recommend
      that patients undergo molecular genetic evaluation. This review discusses the
      clinical and pathological findings of patients with familial PTC, such as FAP,
      CNC, Werner syndrome, and Pendred syndrome, and the heterogeneous group of
      familial PTC.

PMID- 22654877
TI  - Stereotactic neurosurgical treatment options for craniopharyngioma.
AB  - Craniopharyngioma are the most common non-glial tumors in childhood. The results
      of different studies indicate that radical excision surgery is not an appropriate
      treatment strategy for childhood craniopharyngioma with hypothalamic involvement.
      Stereotactic neurosurgery provides save, minimal invasive and cost-efficient
      options in the treatment of childhood craniopharyngioma. In this review a summary
      of the contribution of the stereotactic neurosurgery in the interdisciplinary
      treatment regime of childhood craniopharyngioma will be given and discussed in
      detail.

PMID- 22654880
TI  - Human b1 cell frequency: isolation and analysis of human b1 cells.
AB  - Controversy over the frequency of human B1 cells in normal individuals has arisen
      as different labs have begun to employ non-uniform techniques to study this
      population. The phenotypic profile and relative paucity of circulating human B1
      cells place constraints on methodology to identify and isolate this population.
      Multiple steps must be optimized to insure accurate enumeration and optimal
      purification. In the course of working with human B1 cells we have developed a
      successful strategy that provides consistent analysis of B1 cells for frequency
      determination and efficient isolation of B1 cells for functional studies. Here we
      discuss issues attendant to identifying human B1 cells and outline a carefully
      optimized approach that leads to uniform and reproducible data.

PMID- 22654879
TI  - Mast cell: an emerging partner in immune interaction.
AB  - Mast cells (MCs) are currently recognized as effector cells in many settings of
      the immune response, including host defense, immune regulation, allergy, chronic
      inflammation, and autoimmune diseases. MC pleiotropic functions reflect their
      ability to secrete a wide spectrum of preformed or newly synthesized biologically
      active products with pro-inflammatory, anti-inflammatory and/or immunosuppressive
      properties, in response to multiple signals. Moreover, the modulation of MC
      effector phenotypes relies on the interaction of a wide variety of membrane
      molecules involved in cell-cell or cell-extracellular-matrix interaction. The
      delivery of co-stimulatory signals allows MC to specifically communicate with
      immune cells belonging to both innate and acquired immunity, as well as with non
      immune tissue-specific cell types. This article reviews and discusses the
      evidence that MC membrane-expressed molecules play a central role in regulating
      MC priming and activation and in the modulation of innate and adaptive immune
      response not only against host injury, but also in peripheral tolerance and tumor
      surveillance or -escape. The complex expression of MC surface molecules may be
      regarded as a measure of connectivity, with altered patterns of cell-cell
      interaction representing functionally distinct MC states. We will focalize our
      attention on roles and functions of recently discovered molecules involved in the
      cross-talk of MCs with other immune partners.

PMID- 22654878
TI  - Mast cell chemotaxis - chemoattractants and signaling pathways.
AB  - Migration of mast cells is essential for their recruitment within target tissues
      where they play an important role in innate and adaptive immune responses. These
      processes rely on the ability of mast cells to recognize appropriate chemotactic
      stimuli and react to them by a chemotactic response. Another level of
      intercellular communication is attained by production of chemoattractants by
      activated mast cells, which results in accumulation of mast cells and other
      hematopoietic cells at the sites of inflammation. Mast cells express numerous
      surface receptors for various ligands with properties of potent chemoattractants.
      They include the stem cell factor (SCF) recognized by c-Kit, antigen, which binds
      to immunoglobulin E (IgE) anchored to the high affinity IgE receptor
      (FcepsilonRI), highly cytokinergic (HC) IgE recognized by FcepsilonRI, lipid
      mediator sphingosine-1-phosphate (S1P), which binds to G protein-coupled
      receptors (GPCRs). Other large groups of chemoattractants are eicosanoids
      [prostaglandin E(2) and D(2), leukotriene (LT) B(4), LTD(4), and LTC(4), and
      others] and chemokines (CC, CXC, C, and CX3C), which also bind to various GPCRs.
      Further noteworthy chemoattractants are isoforms of transforming growth factor
      (TGF) beta1-3, which are sensitively recognized by TGF-beta serine/threonine type
      I and II beta receptors, adenosine, C1q, C3a, and C5a components of the
      complement, 5-hydroxytryptamine, neuroendocrine peptide catestatin, tumor
      necrosis factor-alpha, and others. Here we discuss the major types of
      chemoattractants recognized by mast cells, their target receptors, as well as
      signaling pathways they utilize. We also briefly deal with methods used for
      studies of mast cell chemotaxis and with ways of how these studies profited from
      the results obtained in other cellular systems.

PMID- 22654881
TI  - Quorum-Sensing in CD4(+) T Cell Homeostasis: A Hypothesis and a Model.
AB  - Homeostasis of lymphocyte numbers is believed to be due to competition between
      cellular populations for a common niche of restricted size, defined by the
      combination of interactions and trophic factors required for cell survival. Here
      we propose a new mechanism: homeostasis of lymphocyte numbers could also be
      achieved by the ability of lymphocytes to perceive the density of their own
      populations. Such a mechanism would be reminiscent of the primordial quorum
      sensing systems used by bacteria, in which some bacteria sense the accumulation
      of bacterial metabolites secreted by other elements of the population, allowing
      them to "count" the number of cells present and adapt their growth accordingly.
      We propose that homeostasis of CD4(+) T cell numbers may occur via a quorum
      sensing-like mechanism, where IL-2 is produced by activated CD4(+) T cells and
      sensed by a population of CD4(+) Treg cells that expresses the high-affinity IL
      2Ralpha-chain and can regulate the number of activated IL-2-producing CD4(+) T
      cells and the total CD4(+) T cell population. In other words, CD4(+) T cell
      populations can restrain their growth by monitoring the number of activated
      cells, thus preventing uncontrolled lymphocyte proliferation during immune
      responses. We hypothesize that malfunction of this quorum-sensing mechanism may
      lead to uncontrolled T cell activation and autoimmunity. Finally, we present a
      mathematical model that describes the key role of IL-2 and quorum-sensing
      mechanisms in CD4(+) T cell homeostasis during an immune response.

PMID- 22654882
TI  - Chemokines and the signaling modules regulating integrin affinity.
AB  - Integrin-mediated adhesion is a general concept referring to a series of adhesive
      phenomena including tethering-rolling, affinity, valency, and binding
      stabilization altogether controlling cell avidity (adhesiveness) for the
      substrate. Arrest chemokines modulate each aspect of integrin activation,
      although integrin affinity regulation has been recognized as the prominent event
      in rapid leukocyte arrest induced by chemokines. A variety of inside-out and
      outside-in signaling mechanisms have been related to the process of integrin
      mediated adhesion in different cellular models, but only few of them have been
      clearly contextualized to rapid integrin affinity modulation by arrest chemokines
      in primary leukocytes. Complex signaling processes triggered by arrest chemokines
      and controlling leukocyte integrin activation have been described for ras-related
      rap and for rho-related small GTPases. We summarize the role of rap and rho small
      GTPases in the regulation of rapid integrin affinity in primary leukocytes and
      provide a modular view of these pro-adhesive signaling events. A potential,
      albeit still speculative, mechanism of rho-mediated regulation of cytoskeletal
      proteins controlling the last step of integrin activation is also discussed. We
      also discuss data suggesting a functional integration between the rho- and rap
      modules of integrin activation. Finally we examine the universality of signaling
      mechanisms regulating integrin triggering by arrest chemokines.

PMID- 22654884
TI  - Regulation of the PKCtheta-NF-kappaB Axis in T Lymphocytes by the Tumor Necrosis
      Factor Receptor Family Member OX40.
AB  - Antigen primed T lymphocytes need to expand and persist to promote adaptive
      immunity. The growth and survival signals that control this are in large part
      provided by the NF-kappaB pathway in activated or effector/memory T cells.
      Although several membrane receptors impact NF-kappaB activation, signaling from
      OX40 (CD134, TNFRSF4), a member of the tumor necrosis factor receptor (TNFR)
      superfamily, has proven to be important for T cell immunity and a strong
      contributor to NF-kappaB activity. PKCtheta directs the T cell receptor (TCR) and
      CD28-dependent assembly of a CBM complex (CARMA1, BCL10, and MALT1) for efficient
      activation of NF-kappaB, raising the question of whether other membrane bound
      receptors that activate NF-kappaB also require this PKCtheta-CBM axis to control
      TCR-independent T cell activity. We discuss here our recent data demonstrating
      that after ligation by OX40L (CD252, TNFSF4) expressed on antigen-presenting
      cells, OX40 translocates into detergent-insoluble membrane lipid microdomains
      (DIM or lipid rafts) in T cells irrespective of TCR signals, and assembles into a
      signaling complex containing PKCtheta, together with TRAF2, RIP1, the CBM
      complex, and the IKKalpha/beta/Gamma complex. PKCtheta is required for optimal NF
      kappaB activation mediated by OX40 and thus works as an essential component of
      this OX40 signalosome. We also discuss the likelihood that other TNFR superfamily
      molecules might complex with PKCtheta in T cells, and whether PKC isoforms may be
      critical to the function of TNFR molecules in general.

PMID- 22654885
TI  - Tolerogenic effect of non-inherited maternal antigens in hematopoietic stem cell
      transplantation.
AB  - Major histocompatibility complex antigens that provoke severe transplant
      reactions are referred to as the human leukocyte antigen (HLA) in human and as
      the H-2 in mice. Even if the donor and recipient are HLA-identical siblings,
      graft-versus-host reactions have been linked to differences in the minor
      histocompatibility antigen. As the chance of finding an HLA-identical sibling
      donor is only 25%, attention has been focused on using alternative donors. An HLA
      mismatched donor with non-inherited maternal antigens (NIMA) is less immunogenic
      than that with non-inherited paternal antigens, because the contact between the
      immune systems of the mother and child during pregnancy affects the immune
      response of the child against NIMA. However, the immunologic effects of
      developmental exposure to NIMA are heterogeneous, and can be either tolerogenic
      or immunogenic. We recently have devised a novel method for predicting the
      tolerogenic effect of NIMA. In this review, we overview the evidence for the
      existence of the NIMA tolerogenic effect, the possible cellular and molecular
      basis of the phenomenon, and its utilization in hematopoietic stem cell
      transplantation. We suggest a future direction for the safe clinical use of this
      phenomenon, fetomaternal tolerance, in the transplantation field.

PMID- 22654883
TI  - Cytoskeleton in mast cell signaling.
AB  - Mast cell activation mediated by the high affinity receptor for IgE (FcepsilonRI)
      is a key event in allergic response and inflammation. Other receptors on mast
      cells, as c-Kit for stem cell factor and G protein-coupled receptors (GPCRs)
      synergistically enhance the FcepsilonRI-mediated release of inflammatory
      mediators. Activation of various signaling pathways in mast cells results in
      changes in cell morphology, adhesion to substrate, exocytosis, and migration.
      Reorganization of cytoskeleton is pivotal in all these processes. Cytoskeletal
      proteins also play an important role in initial stages of FcepsilonRI and other
      surface receptors induced triggering. Highly dynamic microtubules formed by
      alphabeta-tubulin dimers as well as microfilaments build up from polymerized
      actin are affected in activated cells by kinases/phosphatases, Rho GTPases and
      changes in concentration of cytosolic Ca(2+). Also important are nucleation
      proteins; the gamma-tubulin complexes in case of microtubules or Arp 2/3 complex
      with its nucleation promoting factors and formins in case of microfilaments. The
      dynamic nature of microtubules and microfilaments in activated cells depends on
      many associated/regulatory proteins. Changes in rigidity of activated mast cells
      reflect changes in intermediate filaments build up from vimentin. This review
      offers a critical appraisal of current knowledge on the role of cytoskeleton in
      mast cells signaling.

PMID- 22654886
TI  - Modeling a cortical auxin maximum for nodulation: different signatures of
      potential strategies.
AB  - Lateral organ formation from plant roots typically requires the de novo creation
      of a meristem, initiated at the location of a localized auxin maximum. Legume
      roots can form both root nodules and lateral roots. From the basic principles of
      auxin transport and metabolism only a few mechanisms can be inferred for
      increasing the local auxin concentration: increased influx, decreased efflux, and
      (increased) local production. Using computer simulations we investigate the
      different spatio-temporal patterns resulting from each of these mechanisms in the
      context of a root model of a generalized legume. We apply all mechanisms to the
      same group of preselected cells, dubbed the controlled area. We find that each
      mechanism leaves its own characteristic signature. Local production by itself can
      not create a strong auxin maximum. An increase of influx, as is observed in
      lateral root formation, can result in an auxin maximum that is spatially more
      confined than the controlled area. A decrease of efflux on the other hand leads
      to a broad maximum, which is more similar to what is observed for nodule
      primordia. With our prime interest in nodulation, we further investigate the
      dynamics following a decrease of efflux. We find that with a homogeneous change
      in the whole cortex, the first auxin accumulation is observed in the inner
      cortex. The steady state lateral location of this efflux reduced auxin maximum
      can be shifted by slight changes in the ratio of central to peripheral efflux
      carriers. We discuss the implications of this finding in the context of
      determinate and indeterminate nodules, which originate from different cortical
      positions. The patterns we have found are robust under disruption of the
      (artificial) tissue layout. The same patterns are therefore likely to occur in
      many other contexts.

PMID- 22654887
TI  - Fluorescence imaging-based forward genetic screens to identify trafficking
      regulators in plants.
AB  - Coordinated, subcellular trafficking of proteins is one of the fundamental
      properties of the multicellular eukaryotic organisms. Trafficking involves a
      large diversity of compartments, pathways, cargo molecules, and vesicle-sorting
      events. It is also crucial in regulating the localization and, thus, the activity
      of various proteins, but the process is still poorly genetically defined in
      plants. In the past, forward genetics screens had been used to determine the
      function of genes by searching for a specific morphological phenotype in the
      organism population in which mutations had been induced chemically or by
      irradiation. Unfortunately, these straightforward genetic screens turned out to
      be limited in identifying new regulators of intracellular protein transport,
      because mutations affecting essential trafficking pathways often lead to
      lethality. In addition, the use of these approaches has been restricted by
      functional redundancy among trafficking regulators. Screens for mutants that rely
      on the observation of changes in the cellular localization or dynamics of
      fluorescent subcellular markers enable, at least partially, to circumvent these
      issues. Hence, such image-based screens provide the possibility to identify
      either alleles with weak effects or components of the subcellular trafficking
      machinery that have no strong impact on the plant growth.

PMID- 22654888
TI  - Novel insights into regulation of asparagine synthetase in conifers.
AB  - Asparagine, a key amino acid for nitrogen storage and transport in plants, is
      synthesized via the ATP-dependent reaction catalyzed by the enzyme asparagine
      synthetase (AS; EC 6.3.5.4). In this work, we present the molecular analysis of
      two full-length cDNAs that encode asparagine synthetase in maritime pine (Pinus
      pinaster Ait.), PpAS1, and PpAS2. Phylogenetic analyses of the deduced amino acid
      sequences revealed that both genes are class II AS, suggesting an ancient origin
      of these genes in plants. A comparative study of PpAS1 and PpAS2 gene expression
      profiles showed that PpAS1 gene is highly regulated by developmental and
      environmental factors, while PpAS2 is expressed constitutively. To determine the
      molecular mechanisms underpinning the differential expression of PpAS1, the
      promoter region of the gene was isolated and putative binding sites for MYB
      transcription factors were identified. Gel mobility shift assays showed that a
      MYB protein from Pinus taeda (PtMYB1) was able to interact with the promoter
      region of PpAS1. Furthermore, transient expression analyses in pine cells
      revealed a negative effect of PtMYB1 on PpAS1 expression. The potential role of
      MYB factors in the transcriptional regulation of PpAS1 in vascular cells is
      discussed.

PMID- 22654890
TI  - Proteomic investigations of complex I composition: how to define a subunit?
AB  - Complex I is present in almost all aerobic species. Being the largest complex of
      the respiratory chain, it has a central role in energizing biological membranes
      and is essential for many organisms. Bacterial complex I is composed of 14
      subunits that are sufficient to achieve the respiratory functions. Eukaryotic
      enzymes contain orthologs of the 14 bacterial subunits and around 30 additional
      subunits. This complexity suggests either that complex I requires more
      stabilizing subunits in mitochondria or that it fulfills additional functions. In
      many organisms recent work on complex I concentrated on the determination of its
      exact composition. This review summarizes the work done to elucidate complex I
      composition in the model plant Arabidopsis and proposes a model for the
      organization of its 44 confirmed subunits. The comparison of the different
      studies investigating the composition of complex I across species identifies
      sample preparation for the proteomic analysis as critical to differentiate
      between true subunits, assembly factors, or proteins associated with complex I.
      Coupling comparative proteomics with biochemical or genetic studies is thus
      required to define a subunit and its function within the complex.

PMID- 22654889
TI  - Evolution and expression of tandem duplicated maize flavonol synthase genes.
AB  - Flavonoids are specialized compounds widely distributed and with diverse
      functions throughout the plant kingdom and with several benefits for human
      health. In particular, flavonols, synthesized by flavonol synthase (FLS), protect
      plants against UV-B radiation and are essential for male fertility in maize and
      other plants. We have recently characterized a UV-B inducible ZmFLS1,
      corresponding to the first to be described in monocot plants. Interestingly, the
      new assembly of the B73 maize genome revealed the presence of a second putative
      FLS gene (ZmFLS2), with very high identity with ZmFLS1. ZmFLSs expression was
      analyzed in different maize tissues, and by combining electrophoretic mobility
      shift assays and transient expression experiments, we show that both genes are
      direct targets of anthocyanin (C1/PL1 + R/B) and 3-deoxy flavonoid (P1)
      transcriptional regulators. ZmFLS expression analyses show higher levels of both
      transcripts in high altitude landraces than inbred lines, and both genes are
      regulated by UV-B radiation in all lines analyzed. Moreover, the high sequence
      conservation of the ZmFLS promoters between maize lines suggests that the
      differences observed in ZmFLS expression are due to allelic variations in the
      transcription factors that regulate their activities. Finally, we generated
      pFLS1::FLS1-RFP transgenic plants and analyzed ZmFLS1 expression in different
      maize tissues; we found that this enzyme is localized in the ER and the
      perinuclear region.

PMID- 22654891
TI  - The CELLULOSE SYNTHASE-LIKE A and CELLULOSE SYNTHASE-LIKE C families: recent
      advances and future perspectives.
AB  - The CELLULOSE SYNTHASE (CESA) superfamily of proteins contains several sub
      families of closely related CELLULOSE SYNTHASE-LIKE (CSL) sequences. Among these,
      the CSLA and CSLC families are closely related to each other and are the most
      evolutionarily divergent from the CESA family. Significant progress has been made
      with the functional characterization of CSLA and CSLC genes, which have been
      shown to encode enzymes with 1,4-beta-glycan synthase activities involved in the
      biosynthesis of mannan and possibly xyloglucan backbones, respectively. This
      review examines recent work on the CSLA and CSLC families from evolutionary,
      molecular, and biochemical perspectives. We pose a series of questions, whose
      answers likely will provide further insight about the specific functions of
      members of the CSLA and CSLC families and about plant polysaccharide biosynthesis
      is general.

PMID- 22654892
TI  - IMGT-ONTOLOGY 2012.
AB  - Immunogenetics is the science that studies the genetics of the immune system and
      immune responses. Owing to the complexity and diversity of the immune repertoire,
      immunogenetics represents one of the greatest challenges for data interpretation:
      a large biological expertise, a considerable effort of standardization and the
      elaboration of an efficient system for the management of the related knowledge
      were required. IMGT(r), the international ImMunoGeneTics information system(r)
      (http://www.imgt.org) has reached that goal through the building of a unique
      ontology, IMGT-ONTOLOGY, which represents the first ontology for the formal
      representation of knowledge in immunogenetics and immunoinformatics. IMGT
      ONTOLOGY manages the immunogenetics knowledge through diverse facets that rely on
      the seven axioms of the Formal IMGT-ONTOLOGY or IMGT-Kaleidoscope:
      "IDENTIFICATION," "DESCRIPTION," "CLASSIFICATION," "NUMEROTATION,"
      "LOCALIZATION," "ORIENTATION," and "OBTENTION." The concepts of identification,
      description, classification, and numerotation generated from the axioms led to
      the elaboration of the IMGT((r)) standards that constitute the IMGT Scientific
      chart: IMGT(r)standardized keywords (concepts of identification), IMGT(r)
      standardized labels (concepts of description), IMGT(r) standardized gene and
      allele nomenclature (concepts of classification) and IMGT unique numbering and
      IMGT Collier de Perles (concepts of numerotation). IMGT-ONTOLOGY has become the
      global reference in immunogenetics and immunoinformatics for the knowledge
      representation of immunoglobulins (IG) or antibodies, T cell receptors (TR), and
      major histocompatibility (MH) proteins of humans and other vertebrates, proteins
      of the immunoglobulin superfamily (IgSF) and MH superfamily (MhSF), related
      proteins of the immune system (RPI) of vertebrates and invertebrates, therapeutic
      monoclonal antibodies (mAbs), fusion proteins for immune applications (FPIA), and
      composite proteins for clinical applications (CPCA).

PMID- 22654893
TI  - Three ontologies to define phenotype measurement data.
AB  - BACKGROUND: There is an increasing need to integrate phenotype measurement data
      across studies for both human studies and those involving model organisms.
      Current practices allow researchers to access only those data involved in a
      single experiment or multiple experiments utilizing the same protocol. RESULTS:
      Three ontologies were created: Clinical Measurement Ontology, Measurement Method
      Ontology and Experimental Condition Ontology. These ontologies provided the
      framework for integration of rat phenotype data from multiple studies into a
      single resource as well as facilitated data integration from multiple human
      epidemiological studies into a centralized repository. CONCLUSION: An ontology
      based framework for phenotype measurement data affords the ability to
      successfully integrate vital phenotype data into critical resources, regardless
      of underlying technological structures allowing the user to easily query and
      retrieve data from multiple studies.

PMID- 22654894
TI  - Genetic architecture of nest building in mice LG/J * SM/J.
AB  - Maternal care is critical to offspring growth and survival, which is greatly
      improved by building an effective nest. Some suggest that genetic variation and
      underlying genetic effects differ between fitness-related traits and other
      phenotypes. We investigated the genetic architecture of a fitness-related trait,
      nest building, in F(2) female mice intercrossed from inbred strains SM/J and LG/J
      using a QTL analysis for six related nest phenotypes (Presence and Structure pre-
      and postpartum, prepartum Material Used and postpartum Temperature). We found 15
      direct-effect QTLs explaining from 4 to 13% of the phenotypic variation in nest
      building, mostly with non-additive effect. Epistatic analyses revealed 71
      significant epistatic interactions which together explain from 28.4 to 75.5% of
      the variation, indicating an important role for epistasis in the adaptive process
      of nest building behavior in mice. Our results suggest a genetic architecture
      with small direct effects and a larger number of epistatic interactions as
      expected for fitness-related phenotypes.

PMID- 22654895
TI  - Whole-exome sequencing and an iPSC-derived cardiomyocyte model provides a
      powerful platform for gene discovery in left ventricular hypertrophy.
AB  - RATIONALE: Left ventricular hypertrophy (LVH) is a heritable predictor of
      cardiovascular disease, particularly in blacks. OBJECTIVE: Determine the
      feasibility of combining evidence from two distinct but complementary
      experimental approaches to identify novel genetic predictors of increased LV
      mass. METHODS: Whole-exome sequencing (WES) was conducted in seven African
      American sibling trios ascertained on high average familial LV mass indexed to
      height (LVMHT) using Illumina HiSeq technology. Identified missense or nonsense
      (MS/NS) mutations were examined for association with LVMHT using linear mixed
      models adjusted for age, sex, body weight, and familial relationship. To
      functionally assess WES findings, human induced pluripotent stem cell-derived
      cardiomyocytes (induced pluripotent stem cell-CM) were stimulated to induce
      hypertrophy; mRNA sequencing (RNA-seq) was used to determine gene expression
      differences associated with hypertrophy onset. Statistically significant findings
      under both experimental approaches identified LVH candidate genes. Candidate
      genes were further prioritized by seven supportive criteria that included
      additional association tests (two criteria), regional linkage evidence in the
      larger HyperGEN cohort (one criterion), and publically available gene and variant
      based annotations (four criteria). RESULTS: WES reads covered 91% of the target
      capture region (of size 37.2 MB) with an average coverage of 65*. WES identified
      31,426 MS/NS mutations among the 21 individuals. A total of 295 MS/NS variants in
      265 genes were associated with LVMHT with q-value <0.25. Of the 265 WES genes, 44
      were differentially expressed (P < 0.05) in hypertrophied cells. Among the 44
      candidate genes identified, 5, including HLA-B, HTT, MTSS1, SLC5A12, and THBS1,
      met 3 of 7 supporting criteria. THBS1 encodes an adhesive glycoprotein that
      promotes matrix preservation in pressure-overload LVH. THBS1 gene expression was
      34% higher in hypertrophied cells (P = 0.0003) and a predicted conserved and
      damaging NS variant in exon 13 (A2099G) was significantly associated with LVHMT
      (P = 4 * 10(-6)). CONCLUSION: Combining evidence from cutting-edge genetic and
      cellular experiments can enable identification of novel LVH risk loci.

PMID- 22654897
TI  - Fatty Acid Accumulation and Resulting PPARalpha Activation in Fibroblasts due to
      Trifunctional Protein Deficiency.
AB  - To examine fatty acid accumulation and its toxic effects in cells, we analyzed
      skin fibroblasts from six patients with mitochondrial trifunctional protein
      deficiency, who had abnormalities in the second through fourth reactions in fatty
      acid beta-oxidation system. We found free fatty acid accumulation, enhanced three
      acyl-CoA dehydrogenases, catalyzing the first reaction in the beta-oxidation
      system and being assumed to have normal activities in these patients, and
      PPARalpha activation that was confirmed in the experiments using MK886, a
      PPARalpha specific antagonist and fenofibrate, a PPARalpha specific agonist.
      These novel findings suggest that the fatty acid accumulation and the resulting
      PPARalpha activation are major causes of the increase in the beta-oxidation
      ability as probable compensation for fatty acid metabolism in the patients'
      fibroblasts, and that enhanced cell proliferation and increased oxidative stress
      due to the PPARalpha activation relate to the development of specific clinical
      features such as hypertrophic cardiomyopathy, slight hepatomegaly, and skeletal
      myopathy. Additionally, significant suppression of the PPARalpha activation by
      means of MK886 treatment is assumed to provide a new method of treating this
      deficiency.

PMID- 22654898
TI  - Preoperative FDG-PET/CT Is an Important Tool in the Management of Patients with
      Thick (T4) Melanoma.
AB  - The yield of preoperative PET/CT (PET/CT) for regional and distant metastases for
      thin/intermediate thickness melanoma is low. Objective of this study is to
      determine if PET/CT performed for T4 melanomas helps guide management and alter
      treatment plans. Methods. Retrospective cohort of 216 patients with T4 melanomas
      treated at two tertiary institutions. Fifty-six patients met our inclusion
      criteria (T4 lesion, PET/CT and no clinical evidence of metastatic disease).
      Results. Fifty-six patients (M: 32, F: 24) with median tumor thickness of 6 mm
      were identified. PET/CT recognized twelve with regional and four patients with
      metastatic disease. Melanoma-related treatment plan was altered in 11% of the
      cases based on PET/CT findings. PET/CT was negative 60% of the time, in 35% of
      the cases; it identified incidental findings that required further evaluation.
      Conclusion. Patients with T4 lesions, PET/CT changed the treatment plan 18% of
      the time. Regional findings changed the surgical treatment plan in 11% and the
      adjuvant plan in 7% of our cases due to the finding of metastatic disease.
      Additionally 20 patients had incidental findings that required further workup. In
      this subset of patients, we feel there is a benefit to PET/CT, and further
      studies should be performed to validate our findings.

PMID- 22654899
TI  - Hyperthermic intraoperative thoracoabdominal chemotherapy.
AB  - Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy
      (HIPEC) is a treatment option for selected patients with pseudomyxoma peritonei
      (PMP) and diffuse malignant peritoneal mesothelioma (DMPM). Tumor infiltration of
      the hemidiaphragm requiring partial resection occurs as a result of large volume
      and/or invasive disease at this anatomic site. Transmission of disease from
      abdomen to chest is a great danger in this group of patients. From a prospective
      database, patients who had diaphragm resection and then hyperthermic
      thoracoabdominal chemotherapy (HITAC) as a component of a cytoreductive surgical
      procedure were identified. Data from control patients receiving HIPEC or
      hyperthermic intrathoracic chemotherapy (HITOC) were analyzed for comparison. The
      morbidity, mortality, survival, and recurrence rate within the thoracic space
      were presented. Thirty patients had partial resection of a hemidiaphragm as part
      of a cytoreductive surgical procedure that utilized HITAC. The pharmacologic
      benefit of intracavitary chemotherapy administration was documented with an area
      under the curve ratio of intracavitary concentration times time to plasma
      concentration times time of 27 +/- 10 for mitomycin C and 75 +/- 26 for
      doxorubicin. Comparing percent chemotherapy absorbed for a ninety-minute
      treatment showed the largest for HIPEC, then for HITAC, and lowest for HITOC. The
      incidence of grade 3 and 4 adverse events was 43%. There was no mortality.
      Adjustments in the chemotherapy dose are not necessary with HITAC. The morbidity
      was high, the survival was acceptable, and intrathoracic recurrence was low.

PMID- 22654896
TI  - PPARs: Interference with Warburg' Effect and Clinical Anticancer Trials.
AB  - The metabolic/cell signaling basis of Warburg's effect ("aerobic glycolysis") and
      the general metabolic phenotype adopted by cancer cells are first reviewed.
      Several bypasses are adopted to provide a panoramic integrated view of tumoral
      metabolism, by attributing a central signaling role to hypoxia-induced factor
      (HIF-1) in the expression of aerobic glycolysis. The cancer metabolic phenotype
      also results from alterations of other routes involving ras, myc, p53, and Akt
      signaling and the propensity of cancer cells to develop signaling aberrances
      (notably aberrant surface receptor expression) which, when present, offer unique
      opportunities for therapeutic interventions. The rationale for various emerging
      strategies for cancer treatment is presented along with mechanisms by which PPAR
      ligands might interfere directly with tumoral metabolism and promote anticancer
      activity. Clinical trials using PPAR ligands are reviewed and followed by
      concluding remarks and perspectives for future studies. A therapeutic need to
      associate PPAR ligands with other anticancer agents is perhaps an important
      lesson to be learned from the results of the clinical trials conducted to date.

PMID- 22654900
TI  - The Spectrum of Endoscopic Ultrasound Intervention in Biliary Diseases: A Single
      Center's Experience in 31 Cases.
AB  - Background and Aim. EUS-guided intervention (EGI) for biliary therapy has been
      increasingly used in recent years. This report aims to describe the spectrum and
      experience of EUS-guided interventions in biliary diseases in a single-tertiary
      center. Methods. All patients with EGI were analyzed retrospectively by
      retrieving data from a prospectively stored endoscopic database between January
      2006 and September 2010. Results. There were 31 cases with EGIs (17 female, 14
      male) with a mean age +/- SD of 58.03 +/- 16.89 years. The majority of cases
      (17/31; 55%) were ampullary or pancreatic cancers with obstructive jaundice. The
      major indications for EGI were obstructive jaundice (n = 16) and cholangitis (n =
      9). The EGIs were technically successful in 24 of the 31 cases (77%). The success
      rate for the first 3 years was 8 of 13 procedures (61.5%) as compared to that of
      the last 2 years (16/18 procedures (89%); P = 0.072). Twenty-three of the 24
      cases (96%) with technical success for stent placement also had clinical success
      in terms of symptom improvement. The complications were major in 4 (13%) and
      minor in 7 (23%) patients. Conclusion. The EUS-guided drainage for biliary
      obstruction, acute cholecystitis, bile leak, and biloma was an attractive
      alternative and should be handled in expert centers.

PMID- 22654901
TI  - Calculated tumor volume is an independent predictor of biochemical recurrence in
      patients who underwent retropubic radical prostatectomy.
AB  - Purpose. The purpose of this study is to investigate whether the
      clinicopathological biopsy findings can predict the oncological outcome in
      patients who undergo radical prostatectomy. Materials and Methods. Between
      January 1997 and March 2006, 255 patients with clinically localized
      adenocarcinoma of the prostate (clinical T1-3N0M0) who had undergone retropubic
      radical prostatectomy were enrolled in this study. None of the patients received
      neoadjuvant or adjuvant therapy. Clinicopathological parameters were assessed to
      determine a predictive parameter of biochemical recurrence. Results. Of the total
      255 patients, 77 showed biochemical recurrence during the follow-up period. The
      estimated 5-year overall survival, 5-year cause-specific survival, and 5-year
      biochemical recurrence-free survival rates were 97.7%, 99.5%, and 67.3%,
      respectively. Multivariate analysis using the Cox proportional hazards model
      showed that calculated cancer volume was an independent predictor among the
      preoperative clinicopathological parameters (P < 0.05). SVI and PSM were
      independent predictors among the postoperative parameters (SVI; P < 0.001, PSM; P
      = 0.049). Among the significant preoperative and postoperative parameters,
      calculated cancer volume remained an independent predictive parameter in
      multivariate analysis (P < 0.01). Conclusions. Tumor volume, as calculated by
      preoperative parameters, is an independent predictor of biochemical recurrence in
      patients who had undergone radical prostatectomy.

PMID- 22654902
TI  - The 2011 WPATH Standards of Care and Penile Reconstruction in Female-to-Male
      Transsexual Individuals.
AB  - The World Professional Association for Transgender Health (WPATH) currently
      publishes the Standards of Care (SOC), to provide clinical guidelines for health
      care of transsexual, transgender and gender non-conforming persons in order to
      maximize health and well-being by revealing gender dysphoria. An updated version
      (7th version, 2011) of the WPATH SOC is currently available. Differences between
      the 6th and the 7th versions of the SOC are shown; the SOC relevant to penile
      reconstruction in female-to-male (FtM) persons are emphasized, and we analyze how
      the 2011 WPATH SOC is influencing the daily practice of physicians involved in
      performing a penile reconstruction procedure for these patients. Depending by an
      individual's goals and expectations, the most appropriate surgical technique
      should be performed: the clinic performing penile reconstruction should be able
      to offer the whole range of techniques, such as: metoidioplasty, pedicle and free
      flaps phalloplasty procedures. The goals that physicians and health care
      institutions should achieve in the next years, in order to improve the care of
      female-to-male persons, consist in: informing in details the individuals applying
      for penile reconstruction about all the implications; referring specific
      individuals to centers capable to deliver a particular surgical technique;
      implementing the surgery with the most updated refinements.

PMID- 22654903
TI  - Dyslipidemia and blood-brain barrier integrity in Alzheimer's disease.
AB  - Background. Blood-brain barrier (BBB) dysfunction may have a significant role in
      the pathogenesis of Alzheimer's disease (AD). Modifiable factors associated with
      BBB function may have therapeutic implication. This study tested the hypothesis
      that dyslipidemia is associated with BBB impairment in mild-to-moderate AD.
      Methods. Thirty-six subjects with AD were followed for 1 year. Fasting CSF and
      plasma were collected with clinical assessments at baseline and 12 months. BBB
      impairment was defined as CSF albumin index >=9. Independent t-tests and linear
      regression assessed the relationship between plasma lipoproteins and BBB
      integrity. Results. Dyslipidemia was prevalent in 47% of the population, and in
      75% of those with BBB impairment. Subjects with BBB impairment had significantly
      higher mean plasma triglyceride and lower HDL cholesterol (TG, P = 0.007; HDL, P
      = 0.043). Plasma triglycerides explained 22% of the variance in BBB integrity and
      remained significant after controlling for age, gender, ApoE-4 genotype, blood
      pressure, and statin use. Conclusion. Dyslipidemia is more prevalent in AD
      subjects with BBB impairment. Plasma triglyceride and HDL cholesterol may have a
      role in maintaining BBB integrity in mild-to-moderate Alzheimer's disease.

PMID- 22654904
TI  - The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription
      for the Pathogenesis of Obesity-Associated Dementia.
AB  - Epidemiological studies suggest that being obese in midlife is a risk factor for
      cognitive decline and dementia in later life. Hyperinsulinemia is one of the most
      frequent endocrine features in overweight people which results in insulin
      desensitization. Thus, chronically high insulin levels have been identified as
      risk factor for dementia. Accordingly, chronically high insulin levels might be
      harmful for brain function. Furthermore, insulin and IGF-1-induced signaling is
      reduced in the brains of patients suffering from Alzheimer's disease (AD).
      Interestingly, studies in rodents suggest that reduced insulin receptor (IR) and
      insulin-like growth factor-1 receptor (IGF-1R) signaling decrease AD pathology,
      that is, beta-amyloid toxicity. Data obtained in C. elegans indicate that the
      beneficial effect mediated via reduced IR/IGF-1R signaling might partially be
      induced via the forkhead-box O transcription factors (FoxO). In the mammalian
      brain, there are FoxO1, FoxO3a, and FoxO6 expressed. Surprisingly, high-fat diet
      specifically reduces the expression of FoxO3a and FoxO6 suggesting that IR/IGF-1 
      > FoxO-mediated transcription is involved in the pathogenesis of obesity
      associated cognitive impairment. Therefore, the function of FoxO1 and FoxO3a has
      been investigated in animal models of Alzheimer's disease in detail. The current
      paper focuses on the role of IR/IGF-1 signaling and IR/IGF-1 -> FoxO-mediated
      transcription for the pathogenesis of obesity-associated dementia.

PMID- 22654905
TI  - Gestational diabetes and thyroid autoimmunity.
AB  - Background. About 10% of pregnancies are complicated by previously unknown
      impairment of glucose metabolism, which is defined as gestational diabetes. There
      are little data available on prevalence of thyroid disorders in patients affected
      by gestational diabetes, and about their postgestational thyroid function and
      autoimmunity. We therefore investigated pancreatic and thyroid autoimmunity in
      gestational diabetic patients and in women who had had a previous gestational
      diabetic pregnancy. Methods. We investigated 126 pregnant women at the time of a
      100-g oral glucose tolerance test: 91 were classified as gestational diabetics,
      and 35 were negative (controls). We also studied 69 women who had delivered a
      baby 18-120 months prior to this investigation and who were classified at that
      time gestational diabetics (38 women) or normally pregnant (31 women; controls).
      Results. Our data show no differences for both thyroid function and prevalence of
      autoimmune disorders during pregnancy; however, a significant increase in thyroid
      autoimmunity was seen in women previously affected by gestational diabetes. This
      increased prevalence of thyroid autoimmunity was not associated with the
      development of impaired glucose metabolism after pregnancy. Conclusions. Our data
      suggest that maternal hyperglycemia is a risk factor for the development of
      thyroid autoimmunity, a conclusion that should now be confirmed in a larger
      cohort of patients.

PMID- 22654906
TI  - Regulation and roles of urocortins in the vascular system.
AB  - Urocortins (Ucns) are members of the corticotropin-releasing factor (CRF) family
      of peptides. Ucns would have potent effects on the cardiovascular system via the
      CRF receptor type 2 (CRF(2) receptor). Regulation and roles of each Ucn have been
      determined in the vascular system. Ucns have more potent vasodilatory effects
      than CRF. Human umbilical vein endothelial cells (HUVECs) express Ucns1-3 mRNAs,
      and the receptor, CRF(2a) receptor mRNA. Ucns1-3 mRNA levels are differentially
      regulated in HUVECs. Differential regulation of Ucns may suggest differential
      roles of those in HUVECs. Ucn1 and Ucn2 have strong effects on interleukin (IL)-6
      gene expression and secretion in rat aortic smooth muscle A7r5 cells. The
      increase that we observed in IL-6 levels following Ucn treatment of A7r5 cells
      suggests that smooth muscle cells may be a source of IL-6 secretion under
      physiological stress conditions. Ucns are important and unique modulators of
      vascular smooth muscle cells and act directly or indirectly as autocrine and
      paracrine factors in the vascular system.

PMID- 22654907
TI  - Fluorescence In Situ Hybridization for MicroRNA Detection in Archived Oral Cancer
      Tissues.
AB  - The noncoding RNA designated as microRNA (miRNA) is a large group of small single
      stranded regulatory RNA and has generated wide-spread interest in human disease
      studies. To facilitate delineating the role of microRNAs in cancer pathology, we
      sought to explore the feasibility of detecting microRNA expression in formalin
      fixed paraffin-embedded (FFPE) tissues. Using FFPE materials, we have compared
      fluorescent in situ hybridization (FISH) procedures to detect miR-146a with (a)
      different synthetic probes: regular custom DNA oligonucleotides versus locked
      nucleic acid (LNA) incorporated DNA oligonucleotides; (b) different reporters for
      the probes: biotin versus digoxigenin (DIG); (c) different visualization:
      traditional versus tyramide signal amplification (TSA) system; (d) different
      blocking reagents for endogenous peroxidase. Finally, we performed miR-146a FISH
      on a commercially available oral cancer tissue microarray, which contains 40
      cases of oral squamous cell carcinoma (OSCC) and 10 cases of normal epithelia
      from the human oral cavity. A sample FISH protocol for detecting miR-146a is
      provided. In summary, we have established reliable in situ hybridization
      procedures for detecting the expression of microRNA in FFPE oral cancer tissues.
      This method is an important tool for studies on the involvement of microRNA in
      oral cancer pathology and may have potential prognostic or diagnostic value.

PMID- 22654908
TI  - Dental status and associated factors in a dentate adult population in bulgaria: a
      cross-sectional survey.
AB  - This study aimed to determine variations in the dental status of a dentate adult
      population in terms of "decayed," "missing," and "filled" teeth in relation to
      several sociodemographic and behavioral factors. Quota sampling was used to draw
      2531 subjects aged 20 years and over. Data were collected by means of a
      questionnaire and an oral examination. Multiple logistic regression analyses were
      performed to observe associations between "decayed," "missing," and "filled"
      teeth and the factors of interest. The mean numbers of "decayed," "missing," and
      "filled" teeth were 2.2, 6.7, and 4.9, respectively. Molar teeth were
      significantly more often "missing" than premolar and anterior teeth. Age, gender,
      education, and tooth brushing revealed most noticeable associations. Increasing
      age was associated with a lower chance of having "decayed" and "filled" teeth,
      but with a higher chance of having "missing" teeth. Females were more likely to
      have "missing" and "filled" teeth. Higher education was associated with a lower
      chance of having "missing" teeth. More frequent tooth brushing was associated
      with a lower chance of having "decayed" and "missing" teeth, but with a higher
      chance of having "filled" teeth. These risk indicators should be considered in
      prevention program planning if reduction of tooth loss is to be achieved.

PMID- 22654909
TI  - Clinical and radiographic evaluation of a resin-based root canal sealer: 10-year
      recall data.
AB  - Objectives. This retrospective clinical and radiographical study evaluated the 10
      year outcome of one-visit endodontic treatment with gutta-percha and a
      methacrylate resin-based sealer. Methods. From an initial sample size of 180
      patients, 89 patients with 175 root canals responded to a recall. Treatment
      outcome was based on predetermined clinical and radiographic criteria. Results.
      Root canals had been adequately filled to the working length in 80 teeth
      (89.88%), short in 6 instances (6.74%), while 3 (3.37%) with extrusion immediate
      postoperatively, showed no sealer in periradicular tissues. The difference in the
      outcomes of treatments with respect to age, gender, preoperative pulp or
      periapical status, the size of periapical lesions and the type of permanent
      restorations were not statistically significantly different (P > 0.05). Overall,
      7 (7.86%) cases were considered clinically and radiographically a failure. A life
      table analysis showed a cumulative probability of success of 92.13% after 10
      years with a 95% confidence interval of 83.0 to 94.0. Conclusions. The results of
      this retrospective clinical and radiographical study suggest that the tested
      methacrylate-resin based sealer used with gutta-percha performed similarly to
      other root canal sealers over a period 10 years. Clinical Implications.
      Considering the success rate after 10 years of this methacrylate resin-based
      sealer can be recommended as an alternative to other commonly used root canal
      sealers.

PMID- 22654910
TI  - Rapid Screening for Flavone C-Glycosides in the Leaves of Different Species of
      Bamboo and Simultaneous Quantitation of Four Marker Compounds by HPLC-UV/DAD.
AB  - A strategy for analyzing flavone C-glucosides in the leaves of different species
      of bamboo was developed. Firstly, the flavone C-glycosides were extracted from
      the bamboo leaves (51 species in 17 genera) with methanol and chromatographed on
      silica gel 60 plates in automatic developing chamber (ADC2), and a qualitative
      survey using simple derivatization steps with the NP reagent was carried out. The
      flavone C-glycosides were found in 40 of 51 species of bamboo examined. Secondly,
      an HPLC method with photodiode array and multiple wavelength detector was
      optimized and validated for the simultaneous determination of flavone C
      glycosides, including isoorientin, isovitexin, orientin, and vitexin in the
      leaves of three species of bamboo and the flavone C-glycosides were confirmed by
      LC/MS. The optimized HPLC method proved to be linear in the concentration range
      tested (0.2-100 MUg/mL, r(2) >= 0.9997), precise (RSD <= 1.56%), and accurate (88
      106%). The concentration ranges of isoorientin, isovitexin, orientin, and vitexin
      in three bamboo leaves samples were 1.00-2.78, 0-0.31, 0-0.07, and 0.20-0.68
      mg/g, respectively. The proposed method was validated to be simple and reliable
      and can be a tool for quality control of bamboo leaf extract or its commercial
      products.

PMID- 22654911
TI  - MAP1B Interaction with the FW Domain of the Autophagic Receptor Nbr1 Facilitates
      Its Association to the Microtubule Network.
AB  - Selective autophagy is a process whereby specific targeted cargo proteins,
      aggregates, or organelles are sequestered into double-membrane-bound phagophores
      before fusion with the lysosome for protein degradation. It has been demonstrated
      that the microtubule network is important for the formation and movement of
      autophagosomes. Nbr1 is a selective cargo receptor that through its interaction
      with LC3 recruits ubiquitinated proteins for autophagic degradation. This study
      demonstrates an interaction between the evolutionarily conserved FW domain of
      Nbr1 with the microtubule-associated protein MAP1B. Upon autophagy induction,
      MAP1B localisation is focused into discrete vesicles with Nbr1. This
      colocalisation is dependent upon an intact microtubule network as
      depolymerisation by nocodazole treatment abolishes starvation-induced MAP1B
      recruitment to these vesicles. MAP1B is not recruited to autophagosomes for
      protein degradation as blockage of lysosomal acidification does not result in
      significant increased MAP1B protein levels. However, the protein levels of
      phosphorylated MAP1B are significantly increased upon blockage of autophagic
      degradation. This is the first evidence that links the ubiquitin receptor Nbr1,
      which shuttles ubiquitinated proteins to be degraded by autophagy, to the
      microtubule network.

PMID- 22654912
TI  - S-Glutathionylation of Protein Disulfide Isomerase Regulates Estrogen Receptor
      alpha Stability and Function.
AB  - S-Glutathionylation of cysteine residues within target proteins is a
      posttranslational modification that alters structure and function. We have shown
      that S-glutathionylation of protein disulfide isomerase (PDI) disrupts protein
      folding and leads to the activation of the unfolded protein response (UPR). PDI
      is a molecular chaperone for estrogen receptor alpha (ERalpha). Our present data
      show in breast cancer cells that S-glutathionylation of PDI interferes with its
      chaperone activity and abolishes its capacity to form a complex with ERalpha.
      Such drug treatment also reverses estradiol-induced upregulation of c-Myc,
      cyclinD1, and P21(Cip), gene products involved in cell proliferation. Expression
      of an S-glutathionylation refractory PDI mutant diminishes the toxic effects of
      PABA/NO. Thus, redox regulation of PDI causes its S-glutathionylation, thereby
      mediating cell death through activation of the UPR and abrogation of ERalpha
      stability and signaling.

PMID- 22654913
TI  - Oxidative Stress-Induced Diseases via the ASK1 Signaling Pathway.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase
      (MAPK) kinase kinase that activates the downstream MAPKs, c-Jun N-terminal kinase
      (JNK) and p38. ASK1 is activated by various types of stress, such as oxidative
      stress, endoplasmic reticulum stress, and infection, and regulates various
      cellular functions. Recently, it has been reported that ASK1 is associated with
      various diseases induced by oxidative stress. In this review, we introduce recent
      findings of the regulatory mechanisms of ASK1 and the oxidative stress-induced
      diseases mediated by the ASK1 signaling pathway.

PMID- 22654914
TI  - The yin and yang of nrf2-regulated selenoproteins in carcinogenesis.
AB  - The NF-E2-related factor-2 (Nrf2) is a transcription factor which regulates the
      major cellular defense systems and thereby contributes to the prevention of many
      diseases including cancer. Selenium deficiency is associated with a higher cancer
      risk making also this essential trace element a promising candidate for cancer
      prevention. Two selenoproteins, thioredoxin reductase-1 (TrxR1) and glutathione
      peroxidase-2 (GPx2), are targets for Nrf2. Selenium deficiency activates Nrf2 as
      does a TrxR1 knockout making a synergism between both systems plausible. Although
      this might hold true for healthy cells, the interplay may turn into the opposite
      in cancer cells. The induction of the detoxifying and antioxidant enzymes by Nrf2
      will make cancer cells chemoresistant and will protect them against oxidative
      damage. The essential role of TrxR1 in maintaining proliferation makes its
      upregulation in cancer cells detrimental. The anti-inflammatory potential of GPx2
      will help to inhibit cancer initiation and inflammation-triggered promotion, but
      its growth supporting potential will also support tumor growth. This paper
      considers beneficial and adverse consequences of the activation of Nrf2 and the
      selenoproteins which appear to depend on the cancer stage.

PMID- 22654915
TI  - IgG4-Related Disease Is Not Associated with Antibody to the Phospholipase A2
      Receptor.
AB  - Patients with IgG4-related disease (IgG4-RD) share histopathological
      characteristics that are similar across affected organs. The finding of
      infiltration with IgG4+ plasma cells in the proper clinical and histopathological
      contexts connects a large number of clinical entities that were viewed previously
      as separate conditions. The renal involvement in IgG4-RD is usually characterized
      by tubulointerstitial nephritis, but membranous nephropathy has also been
      reported to be one of the renal complications of IgG4-RD. The recent discovery
      that a high proportion of patients with idiopathic membranous nephropathy (IMN)
      have IgG4 autoantibodies to the M-type phospholipase A2 receptor (PLA2R) in the
      circulation and glomerular immune deposits, together with the profound IgG4
      hypergammaglobulinemia and occasional reports of membranous nephropathy in IgG4
      RD, raised the question of a common antigen. To assess the presence of anti-PLA2R
      antibody in patients with IgG4-RD, we screened sera from 28 IgG4-RD patients by
      immunoblot. None of the patients in this cohort had detectable circulating anti
      PLA2R antibodies. This study suggests that despite some clinical and serological
      overlaps between IgG4-RD and IMN,anti-PLA2R antibodies do not play a role in the
      pathogenesis of IgG4-RD. Additional studies of IgG4-RD with evidence of
      membranous nephropathy are important to exclude any definite relationship.

PMID- 22654916
TI  - Histopathologic Overlap between Fibrosing Mediastinitis and IgG4-Related Disease.
AB  - Fibrosing mediastinitis (FM) and IgG4-related disease (IgG4-RD) are two
      fibroinflammatory disorders with potentially overlapping clinical and
      radiological features. In this paper, we looked for histopathologic features of
      IgG4-RD and enumerated infiltrating IgG4-positive plasma cells within mediastinal
      tissue biopsies from FM patients. We identified 15 consecutive FM surgical
      mediastinal tissue biopsies between 1985 and 2006. All patients satisfied the
      clinical and radiological diagnostic criteria for FM. All patients had either
      serological or radiological evidence of prior histoplasmosis or granulomatous
      disease, respectively. Formalin-fixed paraffin-embedded tissue sections of all
      patients were stained for H&E, IgG, and IgG4. Three samples met the predefined
      diagnostic criteria for IgG4-RD. In addition, characteristic histopathologic
      changes of IgG4-RD in the absence of diagnostic numbers of tissue infiltrating
      IgG4-positive plasma cells were seen in a number of additional cases (storiform
      cell-rich fibrosis in 11 cases, lymphoplasmacytic infiltrate in 7 cases, and
      obliterative phlebitis/arteritis in 2 cases). We conclude that up to one-third of
      histoplasmosis or granulomatous-disease-associated FM cases demonstrate
      histopathological features of IgG4-RD spectrum. Whether these changes occur as
      the host immune response against Histoplasma or represent a manifestation of IgG4
      RD remains to be determined. Studies to prospectively identify these cases and
      evaluate their therapeutic responses to glucocorticoids and/or other
      immunosuppressive agents such as rituximab are warranted.

PMID- 22654917
TI  - Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for
      Diagnosis of Patients with IgG4-Related Disease.
AB  - IgG4-related disease is a new disease classification established in Japan in the
      21st century. Patients with IgG4-related disease display hyper-IgG4
      gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and
      good response to glucocorticoids. Since IgG4 overexpression is also observed in
      other disorders, it is necessary to diagnose IgG4-related disease carefully and
      correctly. We therefore sought to determine cutoff values for serum IgG4 and
      IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related
      disease. Patients and Methods. We retrospectively analyzed serum IgG4
      concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of
      132 patients with IgG4-related disease and 48 patients with other disorders.
      Result. Serum IgG4 >135  mg/dl demonstrated a sensitivity of 97.0% and a
      specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG
      ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively.
      IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of
      94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in
      severely fibrotic parts of tissues. Conclusion. Although a recent unanimous
      consensus of all relevant researchers in Japan recently established the
      diagnostic criteria for IgG4-related disease, findings such as ours indicate that
      further discussion is needed.

PMID- 22654918
TI  - Drug discovery models and toxicity testing using embryonic and induced
      pluripotent stem-cell-derived cardiac and neuronal cells.
AB  - Development of induced pluripotent stem cells (iPSCs) using forced expression of
      specific sets of transcription factors has changed the field of stem cell
      research extensively. Two important limitations for research application of
      embryonic stem cells (ESCs), namely, ethical and immunological issues, can be
      circumvented using iPSCs. Since the development of first iPSCs, tremendous effort
      has been directed to the development of methods to increase the efficiency of the
      process and to reduce the extent of genomic modifications associated with the
      reprogramming procedure. The established lineage-specific differentiation
      protocols developed for ESCs are being applied to iPSCs, as they have great
      potential in regenerative medicine for cell therapy, disease modeling either for
      drug development or for fundamental science, and, last but not least, toxicity
      testing. This paper reviews efforts aimed at practical development of iPSC
      differentiation to neural/cardiac lineages and further the use of these iPSCs
      derived cells for drug development and toxicity testing.

PMID- 22654919
TI  - The promise of human induced pluripotent stem cells in dental research.
AB  - Induced pluripotent stem cell-based therapy for treating genetic disorders has
      become an interesting field of research in recent years. However, there is a
      paucity of information regarding the applicability of induced pluripotent stem
      cells in dental research. Recent advances in the use of induced pluripotent stem
      cells have the potential for developing disease-specific iPSC lines in vitro from
      patients. Indeed, this has provided a perfect cell source for disease modeling
      and a better understanding of genetic aberrations, pathogenicity, and drug
      screening. In this paper, we will summarize the recent progress of the disease
      specific iPSC development for various human diseases and try to evaluate the
      possibility of application of iPS technology in dentistry, including its capacity
      for reprogramming some genetic orodental diseases. In addition to the easy
      availability and suitability of dental stem cells, the approach of generating
      patient-specific pluripotent stem cells will undoubtedly benefit patients
      suffering from orodental disorders.

PMID- 22654921
TI  - The impact of state preemption of local smoking restrictions on public health
      protections and changes in social norms.
AB  - INTRODUCTION: Preemption is a legislative or judicial arrangement in which a
      higher level of government precludes lower levels of government from exercising
      authority over a topic. In the area of smoke-free policy, preemption typically
      takes the form of a state law that prevents communities from adopting local
      smoking restrictions. BACKGROUND: A broad consensus exists among tobacco control
      practitioners that preemption adversely impacts tobacco control efforts. This
      paper examines the effect of state provisions preempting local smoking
      restrictions in enclosed public places and workplaces. METHODS: Multiple data
      sources were used to assess the impact of state preemptive laws on the proportion
      of indoor workers covered by smoke-free workplace policies and public support for
      smoke-free policies. We controlled for potential confounding variables. RESULTS:
      State preemptive laws were associated with fewer local ordinances restricting
      smoking, a reduced level of worker protection from secondhand smoke, and reduced
      support for smoke-free policies among current smokers. DISCUSSION: State
      preemptive laws have several effects that could impede progress in secondhand
      smoke protections and broader tobacco control efforts. Conclusion. Practitioners
      and advocates working on other public health issues should familiarize themselves
      with the benefits of local policy making and the potential impact of preemption.

PMID- 22654920
TI  - Pathogenic Mechanisms and In Vitro Diagnosis of AERD.
AB  - Aspirin-exacerbated respiratory disease (AERD) refers to chronic rhinosinusitis,
      nasal polyposis, bronchoconstriction, and/or eosinophilic inflammation in
      asthmatics following the exposure to nonsteroidal anti-inflammatory drugs
      (NSAIDs). A key pathogenic mechanism associated with AERD is the imbalance of
      eicosanoid metabolism focusing on prostanoid and leukotriene pathways in airway
      mucosa as well as blood cells. Genetic and functional metabolic studies on vital
      and non-vital cells pointed to the variability and the crucial role of lipid
      mediators in disease susceptibility and their response to medication.
      Eicosanoids, exemplified by prostaglandin E(2) (PGE(2)) and peptidoleukotrienes
      (pLT), are potential metabolic biomarkers contributing to the AERD phenotype.
      Also other mediators are implicated in the progress of AERD. Considering the
      various pathogenic mechanisms of AERD, a multitude of metabolic and genetic
      markers is suggested to be implicated and were introduced as potential biomarkers
      for in vitro diagnosis during the past decades. Deduced from an eicosanoid
      related pathogenic mechanism, functional tests balancing PGE(2) and pLT as well
      as other eicosanoids from preferentially vital leukocytes demonstrated their
      applicability for in vitro diagnosis of AERD.

PMID- 22654922
TI  - Use of emerging tobacco products in the United States.
AB  - This paper provides the first nationally representative estimates for use of four
      emerging products. Addressing the issue of land-line substitution with cell
      phones, we used a mixed-mode survey to obtain two representative samples of US
      adults. Of 3,240 eligible respondents contacted, 74% completed surveys. In the
      weighted analysis, 13.6% have tried at least one emerging tobacco product; 5.1%
      snus; 8.8% waterpipe; 0.6% dissolvable tobacco products; 1.8% electronic nicotine
      delivery systems (ENDS) products. Daily smokers (25.1%) and nondaily smokers
      (34.9%) were the most likely to have tried at least one of these products,
      compared to former smokers (17.2%) and never smokers (7.7%), P<.001. 18.2% of
      young adults 18-24 and 12.8% of those >24 have tried one of these products,
      P<.01. In multivariable analysis, current daily (5.5, 4.3-7.6), nondaily (6.1,
      4.0-9.3), and former smoking status (2.7, 2.1-3.6) remained significant, as did
      young adults (2.2, 1.6-3.0); males (3.5, 2.8-4.5); higher educational attainment;
      some college (2.7, 1.7-4.2); college degree (2.0, 1.3-3.3). Use of these products
      raises concerns about nonsmokers being at risk for nicotine dependence and
      current smokers maintaining their dependence. Greater awareness of emerging
      tobacco product prevalence and the high risk demographic user groups might inform
      efforts to determine appropriate public health policy and regulatory action.

PMID- 22654923
TI  - A new paradigm for clinical trials in antibiotherapy?

PMID- 22654924
TI  - Practices and perceptions regarding pain and pain management during routine
      childhood immunizations: Findings from a focus-group study with nurses working at
      Toronto Public Health, Ontario.
AB  - INTRODUCTION: Despite the availability of a variety of evidence-based
      interventions, it has previously been reported that the majority of infants and
      children undergo vaccine injections without the benefit of analgesia. Nurses in
      public health administer a substantial number of injections; however, their
      attitudes and practices surrounding acute pain during vaccine injections have not
      been previously explored. METHODS: A focus-group interview was conducted in
      Toronto, Ontario, with 10 nurses who immunize children. Participants reported
      their perceptions and practices with regard to vaccine injection pain and pain
      management. RESULTS: THREE KEY THEMES EMERGED: environmental and process factors,
      perceptions regarding the effectiveness of different analgesic interventions, and
      perceptions regarding pain and fear. Participants reported a lack of control over
      their environment, resulting in fear and discomfort for children. They
      recommended increased support from external partners such as school teachers and
      administrators. Participants reported that pharmacological interventions, such as
      topical local anesthetics, were not used; however, psychological and physical
      interventions were commonly used. Nurses questioned the effectiveness of topical
      anesthetics, and indicated that more education was required regarding effective
      analgesic interventions. Needle pain was reported to be the most prominent
      concern for children undergoing vaccine injections, and children were described
      as being fearful. DISCUSSION: Nurses reported vaccination setting, analgesic
      effectiveness and relative importance given to pain as important factors for pain
      and pain management during vaccine injections. Future studies should explore
      whether additional perspectives are present in vaccinators in other geographical
      regions. The effectiveness of educational resources and pain management programs
      aimed at improving current practices should be investigated.

PMID- 22654925
TI  - The increasing prevalence of clindamycin resistance in Staphylococcus aureus
      isolates in children with head and neck abscesses.
AB  - OBJECTIVE: To retrospectively review trends in clindamycin resistance among
      Staphylococcus aureus head and neck abscesses between January 2000 and June 2008.
      METHODS: Between January 2000 and June 2008, inpatient and out-patient S aureus
      isolates were reviewed for antibiotic susceptibility. In particular, cultures
      from 153 abscesses in the head and neck region were assessed for clindamycin and
      methicillin resistance patterns. RESULTS: Annual clindamycin resistance rates for
      all S aureus isolates, and specifically for S aureus head and neck abscesses,
      revealed concerning levels of clindamycin and methicillin resistance. After 2002,
      the mean clindamycin resistance rate in head and neck abscesses was approximately
      27%. The number of new cases of methicillin-resistant S aureus per year increased
      from four cases in 2000 to 44 cases in 2007. CONCLUSION: Antibiotic resistance
      should be considered following failed empirical therapy of head and neck
      abscesses with clindamycin.

PMID- 22654927
TI  - A pilot survey of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae
      mediated by K pneumoniae serine carbapenemases in a regional referral hospital in
      British Columbia.

PMID- 22654926
TI  - Antiretroviral therapy for adults infected with HIV: Guidelines for health care
      professionals from the Quebec HIV care committee.
AB  - The appropriate use of antiretrovirals reduces morbidity and mortality caused by
      HIV infection. The present article provides health care professionals with a
      practical guide for the use of antiretrovirals. Therapy should be initiated based
      predominantly on clinical presentation and CD4 count, and should consist of three
      active drugs or at least two active drugs when this is not possible, as in cases
      of some treatment-experienced patients. This is the most effective way to achieve
      long-term suppression of viral replication. Selection of individual drugs in the
      regimen should consider the weight of the evidence supporting these choices, as
      well as their tolerability profiles and ease of use, the patients' comorbidities
      and treatment history. Treatment interruption is not recommended, either in
      aviremic patients or in those who have experienced virological failure. Instead,
      the therapeutic regimen should be adjusted to minimize side effects, promote
      adherence and suppress viral replication.

PMID- 22654928
TI  - The value of repeat Clostridium difficile toxin testing during and after an
      outbreak of C difficile-associated diarrhea.
AB  - BACKGROUND: The recent increase in Clostridium difficile-associated diarrhea
      (CDAD) has led to questions about the reproducibility and sensitivity of C
      difficile toxin testing (CDTT). While there have been recommendations to repeat
      CDTT following a negative result, previous studies have failed to show a benefit.
      However, no studies were performed during an outbreak of CDAD. The value of
      repeat CDTT after an initial negative result in patients tested during and after
      an outbreak of CDAD is reported in the present study, as well as the
      reproducibility of CDTT when multiple samples are received and tested on the same
      day. METHODS: The results of CDTT, performed using a cell cytotoxicity assay
      between April 1, 2001, and March 31, 2008, were retrieved and searched for
      patients who had repeat samples tested after an initial negative result. The
      result and the number of days after a negative result were determined using the
      date of the most recent negative test. The cumulative positivity rate was
      calculated by adding all of the repeat positive test results for the days in
      question and dividing by the total number of tests performed during that time.
      RESULTS: A total of 8661 patients submitted 14,991 stool specimens for CDTT
      during the study period. There were 3095 samples that tested positive (20.6%) for
      the toxin. The results were divided into two time periods to reflect the CDAD
      outbreak, which began in April 2002: period 1 (outbreak) was from April 1, 2002,
      to March 31, 2006, and period 2 was from April 1, 2006, to March 31, 2008. The
      rate of positivity was 24.2% during period 1, and 11.6% during period 2
      (P<0.001). Repeat CDTT was performed 619 times on samples received on the same
      day as the initial specimen, and only three (0.5%) were discordant. A total of
      1630 samples were retested within one to seven days of a negative result, and 103
      (6.3%) tested positive (7.8% period 1 and 2.9% period 2; P=0.002). The likelihood
      of a positive result on repeat testing in the first three days after a negative
      result was low (0.9%, 7% and 4%, respectively). The cumulative positivity for
      repeat testing performed in the first three days was 0.9%, 3.3% and 3.5%,
      respectively, and did not differ significantly at day 3 during the period of high
      CDTT positivity (P=0.110). CONCLUSIONS: The value of repeat CDTT, performed using
      a cell cytotoxicity assay, was low in the first three days after an initial
      negative result and was unchanged during a CDAD outbreak.

PMID- 22654929
TI  - The self and schizophrenia: some open issues.

PMID- 22654930
TI  - The core Gestalt of schizophrenia.

PMID- 22654931
TI  - The placebo response: science versus ethics and the vulnerability of the patient.

PMID- 22654932
TI  - Predicting the severity of everyday functional disability in people with
      schizophrenia: cognitive deficits, functional capacity, symptoms, and health
      status.
AB  - Disability is pervasive in schizophrenia and is refractory to current medication
      treatments. Inability to function in everyday settings is responsible for the
      huge indirect costs of schizophrenia, which may be as much as three times larger
      than direct treatment costs for psychotic symptoms. Treatments for disability are
      therefore urgently needed. In order to effectively treat disability, its causes
      must be isolated and targeted; it seems likely that there are multiple causes
      with modest overlap. In this paper, we review the evidence regarding the
      prediction of everyday disability in schizophrenia. We suggest that cognition,
      deficits in functional capacity, certain clinical symptoms, and various
      environmental and societal factors are implicated. Further, we suggest that
      health status variables, recently recognized as pervasive in severe mental
      illness, may also contribute to disability in a manner independent from these
      other better-studied causes. We suggest that health status be considered in the
      overall prediction of real-world functioning and that interventions aimed at
      disability reduction targeting health status may be needed, in addition to
      cognitive enhancement, skills training, and public advocacy for better services.

PMID- 22654935
TI  - Positive mental health: a research agenda.

PMID- 22654934
TI  - Positive mental health: is there a cross-cultural definition?
AB  - SEVEN MODELS FOR CONCEPTUALIZING POSITIVE MENTAL HEALTH ARE REVIEWED: mental
      health as above normal, epitomized by a DSM-IV's Global Assessment of Functioning
      (GAF) score of over 80; mental health as the presence of multiple human strengths
      rather than the absence of weaknesses; mental health conceptualized as maturity;
      mental health as the dominance of positive emotions; mental health as high socio
      emotional intelligence; mental health as subjective well-being; mental health as
      resilience. Safeguards for the study of mental health are suggested, including
      the need to define mental health in terms that are culturally sensitive and
      inclusive, and the need to empirically and longitudinally validate criteria for
      mental health.

PMID- 22654936
TI  - The self-determination theory perspective on positive mental health across
      cultures.

PMID- 22654937
TI  - The clinical role of psychological well-being.

PMID- 22654933
TI  - Classification of feeding and eating disorders: review of evidence and proposals
      for ICD-11.
AB  - Current classification of eating disorders is failing to classify most clinical
      presentations; ignores continuities between child, adolescent and adult
      manifestations; and requires frequent changes of diagnosis to accommodate the
      natural course of these disorders. The classification is divorced from clinical
      practice, and investigators of clinical trials have felt compelled to introduce
      unsystematic modifications. Classification of feeding and eating disorders in ICD
      11 requires substantial changes to remediate the shortcomings. We review evidence
      on the developmental and cross-cultural differences and continuities, course and
      distinctive features of feeding and eating disorders. We make the following
      recommendations: a) feeding and eating disorders should be merged into a single
      grouping with categories applicable across age groups; b) the category of
      anorexia nervosa should be broadened through dropping the requirement for
      amenorrhoea, extending the weight criterion to any significant underweight, and
      extending the cognitive criterion to include developmentally and culturally
      relevant presentations; c) a severity qualifier "with dangerously low body
      weight" should distinguish the severe cases of anorexia nervosa that carry the
      riskiest prognosis; d) bulimia nervosa should be extended to include subjective
      binge eating; e) binge eating disorder should be included as a specific category
      defined by subjective or objective binge eating in the absence of regular
      compensatory behaviour; f) combined eating disorder should classify subjects who
      sequentially or concurrently fulfil criteria for both anorexia and bulimia
      nervosa; g) avoidant/restrictive food intake disorder should classify restricted
      food intake in children or adults that is not accompanied by body weight and
      shape related psychopathology; h) a uniform minimum duration criterion of four
      weeks should apply.

PMID- 22654938
TI  - Healthy personality development and well-being.

PMID- 22654939
TI  - What is health and what is positive? The ICF solution.

PMID- 22654940
TI  - Subjective positive well-being.

PMID- 22654941
TI  - Problems in the definitions of positive mental health.

PMID- 22654942
TI  - Positive mental health: a note of caution.

PMID- 22654943
TI  - Quality of hallucinatory experiences: differences between a clinical and a non
      clinical sample.
AB  - In this study, we asked people from two samples (a clinical one, consisting of
      patients with schizophrenia, and a non-clinical one, including university
      students) to complete the Revised Hallucination Scale (RHS) as a self
      questionnaire. When the participants responded positively to an item, they were
      encouraged to provide further detailed descriptions (i.e., examples of their own
      experiences) concerning that item. We found that the kinds of descriptions
      provided by the two groups were very different. We suggest that it is not
      advisable to explore the presence of hallucinations in non-clinical samples using
      research protocols based exclusively on yes-or-no answers to questionnaires like
      the RHS. Hallucinatory or hallucinatory-like experiences cannot be reliably and
      validly assessed without a precise characterization of the phenomenal quality of
      the experience.

PMID- 22654944
TI  - Outcomes and moderators of a preventive school-based mental health intervention
      for children affected by war in Sri Lanka: a cluster randomized trial.
AB  - We aimed to examine outcomes, moderators and mediators of a preventive school
      based mental health intervention implemented by paraprofessionals in a war
      affected setting in northern Sri Lanka. A cluster randomized trial was employed.
      Subsequent to screening 1,370 children in randomly selected schools, 399 children
      were assigned to an intervention (n=199) or waitlist control condition (n=200).
      The intervention consisted of 15 manualized sessions over 5 weeks of cognitive
      behavioral techniques and creative expressive elements. Assessments took place
      before, 1 week after, and 3 months after the intervention. Primary outcomes
      included post-traumatic stress disorder (PTSD), depressive, and anxiety symptoms.
      No main effects on primary outcomes were identified. A main effect in favor of
      intervention for conduct problems was observed. This effect was stronger for
      younger children. Furthermore, we found intervention benefits for specific
      subgroups. Stronger effects were found for boys with regard to PTSD and anxiety
      symptoms, and for younger children on pro-social behavior. Moreover, we found
      stronger intervention effects on PTSD, anxiety, and function impairment for
      children experiencing lower levels of current war-related stressors. Girls in the
      intervention condition showed smaller reductions on PTSD symptoms than waitlisted
      girls. We conclude that preventive school-based psychosocial interventions in
      volatile areas characterized by ongoing war-related stressors may effectively
      improve indicators of psychological wellbeing and posttraumatic stress-related
      symptoms in some children. However, they may undermine natural recovery for
      others. Further research is necessary to examine how gender, age and current war
      related experiences contribute to differential intervention effects.

PMID- 22654945
TI  - Peer support among persons with severe mental illnesses: a review of evidence and
      experience.
AB  - Peer support is largely considered to represent a recent advance in community
      mental health, introduced in the 1990s as part of the mental health service user
      movement. Actually, peer support has its roots in the moral treatment era
      inaugurated by Pussin and Pinel in France at the end of the 18th century, and has
      re-emerged at different times throughout the history of psychiatry. In its more
      recent form, peer support is rapidly expanding in a number of countries and, as a
      result, has become the focus of considerable research. Thus far, there is
      evidence that peer staff providing conventional mental health services can be
      effective in engaging people into care, reducing the use of emergency rooms and
      hospitals, and reducing substance use among persons with co-occurring substance
      use disorders. When providing peer support that involves positive self
      disclosure, role modeling, and conditional regard, peer staff have also been
      found to increase participants' sense of hope, control, and ability to effect
      changes in their lives; increase their self-care, sense of community belonging,
      and satisfaction with various life domains; and decrease participants' level of
      depression and psychosis.

PMID- 22654946
TI  - Lessons learned in developing community mental health care in Australasia and the
      South Pacific.
AB  - This paper summarizes the findings for the Australasia and Pacific Region of the
      WPA Task Force on Steps, Obstacles and Mistakes to Avoid in the Implementation of
      Community Mental Health Care. We present an overview of mental health services in
      the region; discuss policies, plans and programmes; chart progress towards
      achieving community-oriented services, and detail the lessons learned.

PMID- 22654947
TI  - Mental health consequences of the 2011 Fukushima nuclear disaster: are the
      grandchildren of people living in Hiroshima and Nagasaki during the drop of the
      atomic bomb more vulnerable?

PMID- 22654948
TI  - Proportion of crimes attributable to mental disorders in the Netherlands
      population.

PMID- 22654949
TI  - Are there differences between training curricula on paper and in practice? Views
      of European trainees.

PMID- 22654950
TI  - WPA contribution to the development of the chapter on mental disorders of the ICD
      11.

PMID- 22654951
TI  - Immunological and nonimmunological effects of indoleamine 2,3-dioxygenase on
      breast tumor growth and spontaneous metastasis formation.
AB  - The role of the tryptophan-catabolizing enzyme, indoleamine 2,3-dioxygenase
      (IDO1), in tumor escape and metastasis formation was analyzed using two pairs of
      Ido1+ and Ido1- murine breast cancer cell lines. Ido1 expression in 4T1 cells was
      knocked down by shRNA, and Ido1 expression in NT-5 cells was upregulated by
      stable transfection. Growth of Ido1- tumors and spontaneous metastasis formation
      were inhibited in immunocompetent mice. A higher level of cytotoxic T lymphocytes
      was generated by spleen cells from mice bearing Ido1- tumors than Ido1+ tumors.
      Tumor and metastatic growth was enhanced in immunodeficient mice, confirming an
      intensified immune response in the absence of Ido1 expression. However, Ido1+
      tumors grow faster than Ido1- tumors in immunodeficient SCID/beige mice (lacking
      T, B, and NK cells) suggesting that some Ido1-controlled nonimmunological
      mechanisms may be involved in tumor cell growth regulation. In vitro experiments
      demonstrated that downregulation of Ido1 in tumor cells was associated with
      decreased cell proliferation, increased apoptosis, and changed expression of cell
      cycle regulatory genes, whereas upregulation of Ido1 in the cells had the
      opposite effects. Taken together, our findings indicate that Ido1 expression
      could exert immunological and nonimmunological effects in murine breast tumor
      cells.

PMID- 22654952
TI  - Heparin increases HLA-G levels in primary antiphospholipid syndrome.
AB  - OBJECTIVES: The aim of this study was to investigate the HLA-G serum levels in
      Primary Antiphospholipid Syndrome (PAPS) patients, its impact on clinical and
      laboratory findings, and heparin treatment. METHODS: Forty-four PAPS patients
      were age and gender matched with 43 controls. HLA-G serum levels were measured
      using an enzyme-linked immunosorbent assay (ELISA). RESULTS: An increase in
      soluble HLA-G levels was found in patients compared to controls (3.35 (0-22.9)
      versus 1.1 (0-14), P = 0.017). There were no significant differences in HLA-G
      levels between patients with and without obstetric events, arterial thrombosis,
      venous thrombosis, or stroke. Sixty-six percent of patients were being treated
      with heparin. Interestingly, patients treated with heparin had higher HLA-G
      levels than ones who were not treated with this medication (5 (0-22.9) versus 1.8
      (0-16) ng/mL, P = 0.038). Furthermore, patients on heparin who experienced
      obstetric events had a trend to increased HLA-G levels compared to patients who
      were not on heparin and did not have obstetric events (5.8 (0-22.9) versus 2 (0
      15.2) ng/mL, P = 0.05). CONCLUSION: This is the first study to demonstrate that
      serum HLA-G levels are increased in APS patients. We also demonstrated that
      heparin increases HLA-G levels and may increase tolerance towards autoantigens.

PMID- 22654953
TI  - The metabolism of baicalin in rat and the biological activities of the
      metabolites.
AB  - Baicalin is one of the major bioactive constituents of Scutellariae Radix, but
      the biotransformation of it is poorly understood. In this paper, the metabolism
      of baicalin in rat was studied. Nine metabolites including one new compound were
      isolated and identified structurally. The plausible scheme for the
      biotransformation pathways of baicalin in the rats was deduced. And the main
      metabolites were evaluated for their antioxidation and anti-inflammation
      biological activities for the first time.

PMID- 22654954
TI  - Role of mesotherapy in musculoskeletal pain: opinions from the italian society of
      mesotherapy.
AB  - Mesotherapy is the injection of active substances into the surface layer of the
      skin. This method allows a slower spread, higher levels, and longer lasting
      effects of drugs in the tissues underlying the site of injection (skin, muscle,
      and joint) compared with those following intramuscular injection. This technique
      is useful when a local pharmacological effect is required and relatively high
      doses of drug in the systemic circulation are not. Mesotherapy should only be
      undertaken following a complete clinical workup and subsequent diagnosis.
      Encouraging results have been reported in randomized, controlled clinical trials
      and in observational studies involving patients with various forms of
      musculoskeletal pain. Recommendations by experts from the Italian Society of
      Mesotherapy for appropriate use of mesotherapy in musculoskeletal pain and an
      algorithm for treating localized painful conditions are provided.

PMID- 22654955
TI  - NMDA Receptors of Gastric-Projecting Neurons in the Dorsal Motor Nucleus of the
      Vagus Mediate the Regulation of Gastric Emptying by EA at Weishu (BL21).
AB  - A large number of studies have been conducted to explore the efficacy of
      electroacupuncture (EA) for the treatment of gastrointestinal motility. While
      several lines of evidence addressed the basic mechanism of EA on gastrointestinal
      motility regarding effects of limb and abdomen points, the mechanism for effects
      of the back points on gastric motility still remains unclear. Here we report that
      the NMDA receptor (NMDAR) antagonist kynurenic acid inhibited the gastric
      emptying increase induced by high-intensity EA at BL21 and agonist NMDA enhanced
      the effect of the same treatment. EA at BL21 enhanced NMDAR, but not AMPA
      receptor (AMPAR) component of miniature excitatory postsynaptic current (mEPSC)
      in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). In
      sum, our data demonstrate an important role of NMDAR-mediated synaptic
      transmission of gastric-projecting DMV neurons in mediating EA at BL21-induced
      enhancement of gastric emptying.

PMID- 22654956
TI  - Antileukemic Potential of Momordica charantia Seed Extracts on Human Myeloid
      Leukemic HL60 Cells.
AB  - Momordica charantia (bitter gourd) has been used in the traditional system of
      medicine for the treatment of various diseases. Anticancer activity of M.
      charantia extracts has been demonstrated by numerous in vitro and in vivo
      studies. In the present study, we investigated the differentiation inducing
      potential of fractionated M. charantia seed extracts in human myeloid HL60 cells.
      We found that the HL60 cells treated with the fractionated seed extracts
      differentiated into granulocytic lineage as characterized by NBT staining, CD11b
      expression, and specific esterase activity. The differentiation inducing
      principle was found to be heat-stable, and organic in nature. The differentiation
      was accompanied by a downregulation of c-myc transcript, indicating the
      involvement of c-myc pathway, at least in part, in differentiation. Taken
      together these results indicate that fractionated extracts of M. charantia seeds
      possess differentiation inducing activity and therefore can be evaluated for
      their potential use in differentiation therapy for leukemia in combination with
      other inducers of differentiation.

PMID- 22654957
TI  - A numerical method of reduced complexity for simulating vascular hemodynamics
      using coupled 0D lumped and 1D wave propagation models.
AB  - A computational method of reduced complexity is developed for simulating vascular
      hemodynamics by combination of one-dimensional (1D) wave propagation models for
      the blood vessels with zero-dimensional (0D) lumped models for the
      microcirculation. Despite the reduced dimension, current algorithms used to solve
      the model equations and simulate pressure and flow are rather complex, thereby
      limiting acceptance in the medical field. This complexity mainly arises from the
      methods used to combine the 1D and the 0D model equations. In this paper a
      numerical method is presented that no longer requires additional coupling methods
      and enables random combinations of 1D and 0D models using pressure as only state
      variable. The method is applied to a vascular tree consisting of 60 major
      arteries in the body and the head. Simulated results are realistic. The numerical
      method is stable and shows good convergence.

PMID- 22654958
TI  - Possible patient early diagnosis by ultrasonic noninvasive estimation of thermal
      gradients into tissues based on spectral changes modeling.
AB  - To achieve a precise noninvasive temperature estimation, inside patient tissues,
      would open promising research fields, because its clinic results would provide
      early-diagnosis tools. In fact, detecting changes of thermal origin in ultrasonic
      echo spectra could be useful as an early complementary indicator of infections,
      inflammations, or cancer. But the effective clinic applications to diagnosis of
      thermometry ultrasonic techniques, proposed previously, require additional
      research. Before their implementations with ultrasonic probes and real-time
      electronic and processing systems, rigorous analyses must be still made over
      transient echotraces acquired from well-controlled biological and computational
      phantoms, to improve resolutions and evaluate clinic limitations. It must be
      based on computing improved signal-processing algorithms emulating tissues
      responses. Some related parameters in echo-traces reflected by semiregular
      scattering tissues must be carefully quantified to get a precise processing
      protocols definition. In this paper, approaches for non-invasive spectral
      ultrasonic detection are analyzed. Extensions of author's innovations for
      ultrasonic thermometry are shown and applied to computationally modeled
      echotraces from scattered biological phantoms, attaining high resolution (better
      than 0.1  degrees C). Computer methods are provided for viability evaluation of
      thermal estimation from echoes with distinct noise levels, difficult to be
      interpreted, and its effectiveness is evaluated as possible diagnosis tool in
      scattered tissues like liver.

PMID- 22654959
TI  - Enhancing the signal of corticomuscular coherence.
AB  - The availability of multichannel neuroimaging techniques, such as MEG and EEG,
      provides us with detailed topographical information of the recorded magnetic and
      electric signals and therefore gives us a good overview on the concomitant
      signals generated in the brain. To assess the location and the temporal dynamics
      of neuronal sources with noninvasive recordings, reconstruction tools such as
      beamformers have been shown to be useful. In the current study, we are in
      particular interested in cortical motor control involved in the isometric
      contraction of finger muscles. To this end we are measuring the interaction
      between the dynamics of brain signals and the electrical activity of hand
      muscles. We were interested to find out whether in addition to the well-known
      correlated activity between contralateral primary motor cortex and the hand
      muscles, additional functional connections can be demonstrated. We adopted
      coherence as a functional index and propose a so-called nulling beamformer method
      which is computationally efficient and addresses the localization of multiple
      correlated sources. In simulations of cortico-motor coherence, the proposed
      method was able to correctly localize secondary sources. The application of the
      approach on real electromyographic and magnetoencephalographic data collected
      during an isometric contraction and rest revealed an additional activity in the
      hemisphere ipsilateral to the hand involved in the task.

PMID- 22654960
TI  - Retroperitoneal pararenal isolated neurofibroma: report of a case and review of
      literature.
AB  - The neurofibroma is a tumour of neural origin. This kind of neoplasm, though, is
      generally skin located. Rare cases in deep organs or in the peritoneal cavity are
      also reported in the literature. There are two types of neurofibromas, localized
      and diffuse; the latter is associated with von Recklinghausen disease and always
      occurs together with skin neurofibromas. Here we report the case of a 47-year-old
      man affected by retroperitoneal neurofibroma, but not associated with von
      Recklinghausen disease. A computed tomography (CT) scan described a
      retroperitoneal pararenal lesion with no clear involvement of adjacent viscera.
      We describe the diagnostic modality, treatment planning and the timing of
      treatment of this neoplasm, reviewing also the literature.

PMID- 22654961
TI  - Incidence of squamous-cell carcinoma of the conjunctiva and other eye cancers in
      the NIH-AARP Diet and Health Study.
AB  - PURPOSE: To investigate the risk factors for squamous-cell carcinoma of the
      conjunctiva (SCCC) and other eye cancers in the NIH-AARP Diet and Health Study.
      METHODS: We estimated incidence rates and associations with age, sex,
      race/ethnicity and ultraviolet radiation using Cox proportional hazards models.
      RESULTS: The incidence was 37.3 per 10(6) for all eye cancers (N = 178), 8.4 per
      10(6) for SCCC (N = 40) and 28.9 per 10(6) for other eye cancers (N = 138). For
      all eye cancers, the incidence was lower in women than in men (hazard ratio [HR]
      = 0.38, 95% CI: 0.26, 0.55) and in persons aged <=60 years than those aged >60
      years (HR = 0.51, 95% CI: 0.36, 0.72). The incidence was higher, but not
      statistically significant, in those with an average net erythemal exposure >170
      versus <=170 (HR = 1.19, 95% CI: 0.88, 1.63) and lower in those residing at
      latitudes >35 degrees  versus <=35 degrees  (HR = 0.81, 95% CI: 0.61, 1.09). The
      patterns were similar for SCCC in sex, age, race/ethnicity and average net
      erythemal exposure, but not statistically significant. CONCLUSION: The incidence
      of all eye cancers was associated with male sex and older age. The same patterns
      were observed for SCCC. The associations reported here might be surrogates of
      exposure to ultraviolet radiation, although more follow-up is needed to obtain
      precise results.

PMID- 22654962
TI  - Post-docetaxel therapy in castration resistant prostate cancer - the forest is
      growing in the desert.
AB  - In Europe, prostate cancer is the most common cancer among men with 382.000 new
      cases and 89.000 deaths annually. Historically, androgen deprivation therapy and
      docetaxel based chemotherapy were the only treatments able to improve survival.
      Two studies have been published during last few months regarding the management
      of castration resistant prostate cancer (CRPC) progressed after docetaxel: for
      the first time second line therapies have been demonstrated to improve prognosis
      of these patients. The relevance of these trials is the reintroduction of
      chemotherapy and hormonal therapy in a disease once considered chemotherapy and
      castration resistant. All these data may change the traditional approach to CRPC
      but no evidences have came out from recently closed or ongoing clinical trials
      about the therapeutic algorithm. How to get oriented in this forest? We propose
      that patient's conditions, response and toxicities reported with previous
      treatments and, above all, dynamics and evolution of disease may influence the
      choice of subsequent therapies in docetaxel progressed CRPC.

PMID- 22654963
TI  - Radiation treatment for patients with intermediate-risk prostate cancer.
AB  - Around 70% of men presenting with prostate cancer will have organ-confined
      disease, with the majority presenting with low- or intermediate-risk prostate
      cancer. This article reviews the evidence supporting the current standard of care
      in radiation oncology for the evaluation and management of men with intermediate
      risk prostate cancer. Dose escalation, hormonal therapy, combined modality
      therapy, and modern techniques for the delivery of radiation therapy are
      reviewed.

PMID- 22654964
TI  - Experience with radical perineal prostatectomy in the treatment of localized
      prostate cancer.
AB  - Radical perineal prostatectomy is an alternative to the retropubic, robotic
      assisted or the laparoscopic approach and it is one of the oldest surgical
      procedures for prostate cancer, but its use has declined over the past 30 years.
      The desire for lower morbidity, short hospital stay, and decreased costs has
      resulted in a renaissance of radical perineal prostatectomy. The combination of
      low morbidity, short hospital stay, and low economic costs brought to a
      renaissance of radical perineal prostatectomy.

PMID- 22654965
TI  - Chemotherapy in penile cancer.
AB  - Penile cancer is an aggressive disease and after systemic progression it is
      virtually incurable. While this squamous cell cancer responds to chemotherapy,
      successful treatment of lymphatic metastases can only be achieved with aggressive
      surgical treatment in combination with chemotherapy. However, because penile
      carcinoma is relatively rare there is a paucity of clinical data on the
      chemotherapy for this aggressive disease. Recent advances have included the
      establishment of less toxic regimens incorporating taxanes, while cisplatinum
      remains central to all regimens. Multi-institutional studies are urgently needed
      to advance the multimodal care for patients with penile cancer.

PMID- 22654967
TI  - Mental health: the aspiration to reality gap.

PMID- 22654966
TI  - Bladder cancer in the second trimester of pregnancy: tough decisions. A case
      report with review of the literature.
AB  - We report a rare case of a patient presenting with a nonmuscle invasive
      papillomatosis transitional cell carcinoma of the bladder in the second trimester
      of pregnancy. We describe the management dilemmas encountered and the challenging
      treatment option selected to optimize outcome for the patient and infant. Close
      collaboration between urologists, obstetricians and medical colleagues is needed
      for optimal, safe and effective management of bladder tumours during pregnancy.

PMID- 22654968
TI  - Should development agencies care about mental health?

PMID- 22654969
TI  - Mental health and the global agenda: core conceptual issues.

PMID- 22654970
TI  - Scaling up mental health services: where would the money come from?

PMID- 22654971
TI  - Social, economic, human rights and political challenges to global mental health.

PMID- 22654972
TI  - What action can national and international agencies take?

PMID- 22654973
TI  - International and national policy challenges in mental health.

PMID- 22654974
TI  - How can mental health be integrated into health system strengthening?

PMID- 22654975
TI  - Health system challenges and solutions to improving mental health outcomes.

PMID- 22654976
TI  - Diffuse pulmonary amyloidosis due to Familial Mediterranean Fever, a rare
      presentation.

PMID- 22654977
TI  - Fusionless procedures for the management of early-onset spine deformities in
      2011: what do we know?
AB  - While attempts to understand them better and treat them more effectively, early
      onset deformities have gained great pace in the past few years. Large patient
      series with long follow-ups that would provide high levels of evidence are still
      almost non-existent. That there is no safe treatment algorithm defined and agreed
      upon for this patient population continues to pose a challenge for pediatric
      spine surgeons. In this review, authors who are well known for their research and
      experience in the treatment of early-onset scoliosis (EOS) have come together in
      order to answer those questions which are most frequently asked by other
      surgeons. The most basic eight questions in this field have been answered
      succinctly by these authors and a current overview is provided.

PMID- 22654978
TI  - Intra- and interrater agreement of pressure pain thresholds in children with
      orthopedic disorders.
AB  - PURPOSE: Pressure algometry is widely used to obtain measures of mechanical pain
      sensitivity in adults, both in experimental and clinical pain conditions. Only
      very few studies describe the use of pressure algometry in children. The purpose
      of this study was to produce reference values of pressure pain thresholds and to
      determine the intra- and interrater agreement, in order to introduce pressure
      algometry as a standardized method for the assessment of pain thresholds in
      children with orthopedic disorders. METHODS: Pressure pain thresholds were
      determined at the leg and at the thenar in 50 children aged 4-12 years. All were
      scheduled for physical examination at the outpatient Orthopedic Clinic at Aarhus
      University Hospital, Denmark, because of various orthopedic disorders such as
      clubfoot and Baker's cyst. Pressure pain thresholds were determined by two
      different raters: 20 children were examined twice by rater 1 (intrarater
      agreement), and another 20 children were examined by both rater 1 and rater 2
      (interrater agreement). An additional ten children were examined once by rater 1
      to increase the number of children used to determine the reference values.
      RESULTS: The pressure pain threshold was 183.1 kPa (mean, SD: 90.7) at the leg
      and 179.1 kPa (mean, SD: 97.4 kPa) at the thenar (n = 50). Pressure pain
      thresholds were similar in boys (n = 27) and girls (n = 23). Also, pressure pain
      thresholds were not affected by age. Bland-Altman plots showed excellent
      intrarater agreement and satisfactory interrater agreement. CONCLUSION: Pressure
      algometry has excellent intrarater agreement and satisfactory interrater
      agreement. Pressure algometry was well-tolerated even by very young children. The
      method deserves more widespread use both in clinical and experimental settings.

PMID- 22654979
TI  - The effect of local anaesthetic on post-operative pain with wound instillation
      via a catheter for paediatric orthopaedic extremity surgery.
AB  - PURPOSE: We aimed to investigate the effects on post-operative pain of local
      anaesthetic administration via a catheter placed into the operation site in
      patients who were undergoing upper and lower extremity paediatric orthopaedic
      surgery. METHODS: In this randomised, double-blind and placebo study, 40 ASA I-II
      patients aged between 1 and 12 years were randomly allocated into two groups:
      study group (Group S: 0.2 ml/kg, 0.5% bupivacaine, n = 20) and control group
      (Group C: 0.2 ml/kg, serum physiologic, n = 20). Before the fascia was closed by
      the surgical team, the solution previously prepared by the chief nurse was
      injected into the subfascial soft tissue with the syringe as the "injected dose"
      of serum physiologic or bupivacaine. After the closure, 0.2 ml/kg (1 mg/kg)
      bupivacaine or saline was instillated as the "first instillated dose" into the
      surgical area via the catheter. Pain scores were recorded at 0, 1, 2, 4, 8, 12,
      24 and 48 h post-operatively. Patients were administered 0.75 mg/kg meperidine
      intramuscularly post-operatively to equalise the pain scores. RESULTS: No
      statistically significant difference was found between Group S and Group C in
      terms of demographic and other data and pain scores in the post-anaesthesia care
      unit, while a statistically significant decrease was found at 2, 4, 8, 12, 24 and
      48 h in Group S and at 1, 2 and 4 h in Group C based on pain scores in the post
      anaesthesia care unit (P < 0.05). A statistically significant decreasing pain
      score was found at 4, 8, 12, 24 and 48 h in Group S (P < 0.05). CONCLUSION: The
      local anaesthetic administered via a catheter implanted in the surgical field may
      provide long-term and efficient post-operative analgesia.

PMID- 22654980
TI  - The use of X-ray at 5 months in a selective screening programme for developmental
      dysplasia of the hip.
AB  - BACKGROUND: The methods used for any screening programme for developmental
      dysplasia of the hip (DDH) can be controversial. This was an opportunistic audit
      of our selective ultrasound screening programme using an X-ray at 5 months to
      prevent inappropriate discharge due to the learning curve of ultrasound. METHODS:
      Between 1990 and 2004 in Nottingham, UK, out of a total population of 108,500
      births, approximately 11,500 neonates were screened using ultrasound. Any child
      with an ultrasound scan showing Graf alpha-angles greater than 60 degrees  (Graf
      Type I) with the hip in joint were discharged from the clinic. All of those
      discharged were subsequently X-rayed at 5 months in order to cover the learning
      curve of ultrasound. The X-rays were reviewed by a consultant radiologist and
      referred back to orthopaedics if there was lateralisation of the femoral head or
      an acetabular index above 30 degrees . RESULTS: Of approximately 11,000 X-rays
      performed, only 53 patients were referred back to orthopaedics, of which 47 had a
      complete data set. Of these 47 children, only 8 (17%) required intervention. On
      review of the original ultrasounds, Graf's alpha-angle did not seem to correlate
      well with the need for intervention, as all were Type I hips. The femoral head
      cover (FHC) appeared to be more predictive of the need for treatment. There have
      been no late presentations to our unit of DDH following a normal 5-month X-ray.
      CONCLUSIONS: We now check the Graf alpha-angle, FHC and dynamic stability in the
      ultrasound assessment and only perform X-ray at 5 months if there was a low alpha
      angle or low FHC. Since this change, there have been no late presentations of DDH
      from the population screened by ultrasound.

PMID- 22654981
TI  - Lateral growth arrest of the proximal femoral physis: a new technique for serial
      radiological observation.
AB  - PURPOSE: Lateral growth arrest is recognised as the most common form of avascular
      necrosis (AVN) seen in the management of developmental dysplasia of the hip
      (DDH). The purpose of this report is to present a new technique that is of
      benefit in the early identification and subsequent radiological monitoring of
      lateral growth arrest and which may permit appropriate timely surgical
      intervention. METHODS: We performed a retrospective review of the medical records
      and serial radiographs of 11 patients (three males and eight females) with
      lateral growth disturbance in the proximal femoral physis. We devised a new
      technique (named the 'Tilt angle') for serial radiographic observation of lateral
      growth arrest. RESULTS: This study included 11 hips in 11 patients. Ten patients
      had screw epiphyseodesis performed after progression of lateral growth arrest was
      noted. One patient did not have screw epiphyseodesis but the results for this
      patient are included, as they provide an interesting 'control' case for
      comparison. The average age of screw epiphyseodesis was 12 years. Seven patients
      demonstrated improvement in their tilt angle following screw epiphyseodesis (i.e.
      less valgus), one showed no change and two continued to decline. CONCLUSIONS:
      Using a new technique to monitor the progression of lateral growth arrest, we
      noted that screw epiphyseodesis can be used for guided growth of the proximal
      femoral physis. This technique can be employed for serial radiographic
      observation of lateral growth arrest and can guide the clinician on the optimal
      timing of screw epiphyseodesis. Further studies are needed in order to clarify
      the optimal timing of screw epiphyseodesis.

PMID- 22654982
TI  - Use of the eight-Plate for angular correction of knee deformities due to
      idiopathic and pathologic physis: initiating treatment according to etiology.
AB  - PURPOSE: Angular deformities of the knee resulting from idiopathic, congenital,
      or acquired causes are commonly encountered in pediatric orthopedics. Whereas
      physiological deformities should be treated expectantly, the remaining often
      progress enough to warrant operative treatment, despite attempted bracing.
      Historical methods of surgical treatment (e.g., epiphysiodesis and stapling) have
      yielded to the increasingly popular method of reversible guided growth using the
      eight-Plate. METHODS: We studied 58 patients with knee angular deformities
      managed with eight-Plate guided growth. All etiologies except physiological
      deformities and those with very slow growth rate were included. Each patient was
      under appropriate medical management during the entire duration of treatment and
      after plate removal. RESULTS: In the dysplasia/syndrome group, we noted complete
      correction in 22 patients (78.5%), partial correction in 5 (17.9%), and no
      correction in 1 patient (3.6%). All cases of idiopathic deformities resolved.
      Patients with osteochondral dysplasias and genetic syndromes underwent earlier
      intervention and slower correction than those with idiopathic genu varum or
      valgum. The time difference in reaching a neutral mechanical axis between the two
      groups (11 months in idiopathic versus 18 months in pathological physis) could be
      explained by a significant difference in growth speeds (P = 0.003). CONCLUSION:
      Results indicate that early intervention is advisable for patients with
      osteochondral dysplasias/syndromes as subsequent correction takes longer. If
      rebound growth causing recurrent deformity occurs, guided growth can be safely
      repeated. Additionally, complications reported with other techniques such as
      hardware failure, physeal violation by the implant, premature physeal closure,
      and overcorrection were not reported while using the eight-Plate.

PMID- 22654983
TI  - Fassier-Duval femoral rodding in children with osteogenesis imperfecta receiving
      bisphosphonates: functional outcomes at one year.
AB  - PURPOSE: To examine the functional outcomes of children with osteogenesis
      imperfecta (OI) following initial Fassier-Duval (FD) rodding to the femur at 1
      year, and to determine which factors are associated with change in gross motor
      function, ambulation, and functional performance. METHODS: Approval from our
      Institutional Review Board was obtained. A retrospective chart review identified
      60 children (28 males, 32 females) with OI who underwent initial FD femoral
      rodding (101 rods) and who were receiving bisphosphonates. The mean age of the
      children was 3 years, 11 months at the initial femoral FD rodding. Two had type I
      OI, 30 type III, 27 type IV, and one type VI. The maximum length of follow-up was
      4 years. Telescoping FD rods were used for the femurs, with surgeries performed
      one leg at a time, with a 1-week interval. The active range of motion (AROM) of
      the hips and knees in flexion was measured 4-5 weeks post-initial rodding.
      Outcomes on the Gillette Functional Assessment Questionnaire (FAQ) Ambulation
      Scale, the Gross Motor Function Measure (GMFM), and the Pediatric Evaluation of
      Disability Inventory (PEDI) were compared pre-operatively and at 1 year post
      surgery using t-tests and multivariate linear regression. RESULTS: Pre
      operatively, the mean FAQ score was 2.0, and this increased to 5.8 at 1 year post
      surgery. Statistically significant improvements (P <= 0.05) were found on the
      FAQ, crawling, standing, walking and running, and total domains of the GMFM, and
      PEDI mobility and self-care from baseline to 1 year. The results from the
      multivariate linear regression indicate that older age (P = 0.0045) and higher
      weight (P = 0.0164) are significantly associated with lower scores in the self
      care domain of the PEDI, and that OI type III compared to type IV is
      significantly associated (P = 0.0457) with greater improvement on the crawling
      domain of the GMFM. Higher weight was also associated (P = 0.0289) with lower
      scores in the standing domain of the GMFM, as well as with the total GMFM score
      (P = 0.0398). CONCLUSIONS: Our findings indicate that initial FD femoral rodding
      resulted in benefits in ambulation, gross motor function, self-care, and mobility
      for children with OI beyond physiological expectations due to developmental
      growth. FD rodding is a procedure which can improve the overall mobility in
      children with OI with significant femoral deformities.

PMID- 22654984
TI  - Acute multifocal haematogenous osteomyelitis in children.
AB  - PURPOSE: Haematogenous multifocal osteomyelitis in children represents a
      dangerous form of osteomyelitis in which sepsis can develop quickly if it is not
      treated early. A retrospective analysis of 26 children with acute multifocal
      haematogenous osteomyelitis over a period of 5 years was undertaken in order to
      assess the clinical presentation, infective organism, laboratory investigations
      and risk factors involved. METHODS: Children more than 1 year of age with two or
      more bones involvement presenting within one week from the onset of symptoms were
      included in this study. All of the children were evaluated by clinical
      examination, blood tests and local ultrasound. RESULTS: The average age at
      presentation was 4.9 years and girls were affected more than boys, with a female
      to male ratio of 1.4. Lower limbs were affected in 92% of cases, and,
      specifically, the tibia in 73.1% of the patients. Blood culture was positive in
      38.5% of our cases. The predominant microorganism isolated from surgical samples
      was Staphylococcus aureus, among which methicillin-resistant S. aureus (MRSA) was
      found in 50% of the patients. Surgical drainage of the pus was done in 24 cases,
      followed by appropriate antibiotics, and two cases were treated by conservative
      means. All of the children were successfully treated except for four, who
      developed chronic osteomyelitis and sequelae. CONCLUSION: We conclude that acute
      multifocal haematogenous osteomyelitis in children needs early diagnosis by a
      high index of clinical suspicion and adequate treatment with timely intervention.
      The predominance of MRSA in our study shows the changing trend in its association
      with multiple bone involvement.

PMID- 22654986
TI  - Design of delay-dependent state estimator for discrete-time recurrent neural
      networks with interval discrete and infinite-distributed time-varying delays.
AB  - The state estimation problem for discrete-time recurrent neural networks with
      both interval discrete and infinite-distributed time-varying delays is studied in
      this paper, where interval discrete time-varying delay is in a given range. The
      activation functions are assumed to be globally Lipschitz continuous. A delay
      dependent condition for the existence of state estimators is proposed based on
      new bounding techniques. Via solutions to certain linear matrix inequalities,
      general full-order state estimators are designed that ensure globally asymptotic
      stability. The significant feature is that no inequality is needed for seeking
      upper bounds for the inner product between two vectors, which can reduce the
      conservatism of the criterion by employing the new bounding techniques. Two
      illustrative examples are given to demonstrate the effectiveness and
      applicability of the proposed approach.

PMID- 22654985
TI  - Generalization of learning by synchronous waves: from perceptual organization to
      invariant organization.
AB  - From a few presentations of an object, perceptual systems are able to extract
      invariant properties such that novel presentations are immediately recognized.
      This may be enabled by inferring the set of all representations equivalent under
      certain transformations. We implemented this principle in a neurodynamic model
      that stores activity patterns representing transformed versions of the same
      object in a distributed fashion within maps, such that translation across the map
      corresponds to the relevant transformation. When a pattern on the map is
      activated, this causes activity to spread out as a wave across the map,
      activating all the transformed versions represented. Computational studies
      illustrate the efficacy of the proposed mechanism. The model rapidly learns and
      successfully recognizes rotated and scaled versions of a visual representation
      from a few prior presentations. For topographical maps such as primary visual
      cortex, the mechanism simultaneously represents identity and variation of visual
      percepts whose features change through time.

PMID- 22654987
TI  - Visualization for understanding of neurodynamical systems.
AB  - Complex neurodynamical systems are quite difficult to analyze and understand. New
      type of plots are introduced to help in visualization of high-dimensional
      trajectories and show global picture of the phase space, including relations
      between basins of attractors. Color recurrence plots (RPs) display distances from
      each point on the trajectory to all other points in a two-dimensional matrix.
      Fuzzy Symbolic Dynamics (FSD) plots enhance this information mapping the whole
      trajectory to two or three dimensions. Each coordinate is defined by the value of
      a fuzzy localized membership function, optimized to visualize interesting
      features of the dynamics, showing to which degree a point on the trajectory
      belongs to some neighborhood. The variance of the trajectory within the
      attraction basin plotted against the variance of the synaptic noise provides
      information about sizes and shapes of these basins. Plots that use color to show
      the distance between each trajectory point and a larger number of selected
      reference points (for example centers of attractor basins) are also introduced.
      Activity of 140 neurons in the semantic layer of dyslexia model implemented in
      the Emergent neural simulator is analyzed in details showing different aspects of
      neurodynamics that may be understood in this way. Influence of connectivity and
      various neural properties on network dynamics is illustrated using visualization
      techniques. A number of interesting conclusions about cognitive neurodynamics of
      lexical concept activations are drawn. Changing neural accommodation parameters
      has very strong influence on the dwell time of the trajectories. This may be
      linked to attention deficits disorders observed in autism in case of strong
      enslavement, and to ADHD-like behavior in case of weak enslavement.

PMID- 22654988
TI  - Neuromechanical representation of fabric-evoked prickliness: a fiber-skin-neuron
      model.
AB  - Cutaneous Adelta nociceptors encode the material and geometrical features of
      fiber ends evoking prickliness sensation by generating neural spikes in response
      to indentation of human skin, however, understanding of the underlying
      neuromechanism of fabric-evoked prickliness is still far from clear. This work
      develops and validates a fiber-skin-neuron (mechanosensitive Adelta-nociceptors)
      model that combines an analytical model of fiber-skin indentation, a sigmoidal
      function of neuronal transduction, and a leaky integrate-and-fire model of
      neuronal dynamics. Firstly, the model is validated to be capable of capturing the
      typical neurphysiological features of cutaneous Adelta nociceptors and the
      psychophysical phenomenon. And then, several case studies with respect to
      statistical features of fiber ends are carried out, and the resulting neural
      responses are calculated to explore the relationship between statistical features
      in study and evoked responses. The analysis of predicted action potentials over
      one second indicates that they systematically change with statistical features of
      fiber ends protruding above fabric surfaces, and the fitted stimulus-response
      relationship of Adelta nociceptors is highly similar to the stimulus-sensation
      relationship of prickliness rating magnitude. It follows that there might exist a
      linear relationship between fabric-evoked neurophysiological responses and
      psychophysical responses. These results provide significant new insight into the
      fabric-evoked prickliness sensation and raise interesting questions for further
      investigation, and the model described here bridges the gap between those models
      that transform fiber ends properties to firing rates.

PMID- 22654989
TI  - Complexity measures of brain wave dynamics.
AB  - To understand the nature of brain dynamics as well as to develop novel methods
      for the diagnosis of brain pathologies, recently, a number of complexity measures
      from information theory, chaos theory, and random fractal theory have been
      applied to analyze the EEG data. These measures are crucial in quantifying the
      key notions of neurodynamics, including determinism, stochasticity, causation,
      and correlations. Finding and understanding the relations among these complexity
      measures is thus an important issue. However, this is a difficult task, since the
      foundations of information theory, chaos theory, and random fractal theory are
      very different. To gain significant insights into this issue, we carry out a
      comprehensive comparison study of major complexity measures for EEG signals. We
      find that the variations of commonly used complexity measures with time are
      either similar or reciprocal. While many of these relations are difficult to
      explain intuitively, all of them can be readily understood by relating these
      measures to the values of a multiscale complexity measure, the scale-dependent
      Lyapunov exponent, at specific scales. We further discuss how better indicators
      for epileptic seizures can be constructed.

PMID- 22654990
TI  - An integrated neural model of semantic memory, lexical retrieval and category
      formation, based on a distributed feature representation.
AB  - This work presents a connectionist model of the semantic-lexical system. Model
      assumes that the lexical and semantic aspects of language are memorized in two
      distinct stores, and are then linked together on the basis of previous
      experience, using physiological learning mechanisms. Particular characteristics
      of the model are: (1) the semantic aspects of an object are described by a
      collection of features, whose number may vary between objects. (2) Individual
      features are topologically organized to implement a similarity principle. (3)
      Gamma-band synchronization is used to segment different objects simultaneously.
      (4) The model is able to simulate the formation of categories, assuming that
      objects belong to the same category if they share some features. (5) Homosynaptic
      potentiation and homosynaptic depression are used within the semantic network, to
      create an asymmetric pattern of synapses; this allows a different role to be
      assigned to shared and distinctive features during object reconstruction. (6)
      Features which frequently occurred together, and the corresponding word-forms,
      become linked via reciprocal excitatory synapses. (7) Features in the semantic
      network tend to inhibit words not associated with them during the previous
      learning phase. Simulations show that, after learning, presentation of a cue can
      evoke the overall object and the corresponding word in the lexical area. Word
      presentation, in turn, activates the corresponding features in the sensory-motor
      areas, recreating the same conditions occurred during learning, according to a
      grounded cognition viewpoint. Several words and their conceptual description can
      coexist in the lexical-semantic system exploiting gamma-band time division.
      Schematic exempla are shown, to illustrate the possibility to distinguish between
      words representing a category, and words representing individual members and to
      evaluate the role of gamma-band synchronization in priming. Finally, the model is
      used to simulate patients with focalized lesions, assuming a damage of synaptic
      strength in specific feature areas. Results are critically discussed in view of
      future model extensions and application to real objects. The model represents an
      original effort to incorporate many basic ideas, found in recent conceptual
      theories, within a single quantitative scaffold.

PMID- 22654991
TI  - Fast and robust image segmentation by small-world neural oscillator networks.
AB  - Inspired by the temporal correlation theory of brain functions, researchers have
      presented a number of neural oscillator networks to implement visual scene
      segmentation problems. Recently, it is shown that many biological neural networks
      are typical small-world networks. In this paper, we propose and investigate two
      small-world models derived from the well-known LEGION (locally excitatory and
      globally inhibitory oscillator network) model. To form a small-world network, we
      add a proper proportion of unidirectional shortcuts (random long-range
      connections) to the original LEGION model. With local connections and shortcuts,
      the neural oscillators can not only communicate with neighbors but also exchange
      phase information with remote partners. Model 1 introduces excitatory shortcuts
      to enhance the synchronization within an oscillator group representing the same
      object. Model 2 goes further to replace the global inhibitor with a sparse set of
      inhibitory shortcuts. Simulation results indicate that the proposed small-world
      models could achieve synchronization faster than the original LEGION model and
      are more likely to bind disconnected image regions belonging together. In
      addition, we argue that these two models are more biologically plausible.

PMID- 22654994
TI  - Quantum-like interference effect in gene expression: glucose-lactose destructive
      interference.
AB  - In this note we illustrate on a few examples of cells and proteins behavior that
      microscopic biological systems can exhibit a complex probabilistic behavior which
      cannot be described by classical probabilistic dynamics. These examples support
      authors conjecture that behavior of microscopic biological systems can be
      described by quantum-like models, i.e., models inspired by quantum-mechanics. At
      the same time we do not couple quantum-like behavior with quantum physical
      processes in bio-systems. We present arguments that such a behavior can be
      induced by information complexity of even smallest bio-systems, their adaptivity
      to context changes. Although our examples of the quantum-like behavior are rather
      simple (lactose-glucose interference in E. coli growth, interference effect for
      differentiation of tooth stem cell induced by the presence of mesenchymal cell,
      interference in behavior of PrP(C) and PrP(Sc) prions), these examples may
      stimulate the interest in systems biology to quantum-like models of adaptive
      dynamics and lead to more complex examples of nonclassical probabilistic behavior
      in molecular biology.

PMID- 22654992
TI  - Extracellular matrix bioengineering and systems biology approaches in liver
      disease.
AB  - The extracellular matrix (ECM) in the liver as well as in many organs comprises a
      peripheral network linking numerous macromolecules typically classified into
      collagens, microfibrillar proteins, proteoglycans, chemokines, growth factors and
      glycoproteins. In addition to its role as an essential structural and
      physiological component, it plays a vital role in driving key cellular events
      such as cell adhesion, migration, proliferation, differentiation and survival.
      Any structural inherited or acquired defect and/or metabolic or pathologic
      alteration in the hepatic ECM may cause cellular and organ responses leading to
      the development or progression of liver disease. Therefore, the ECM molecules are
      key players in tissue engraftment and in the pathophysiology of liver disease. In
      this review we provide a snapshot on current efforts for understanding its role
      in physiological and non-physiological states, by describing how tissue
      engineering platforms can enhance in vitro and in vivo models of liver disease,
      by providing examples where bioengineered ECM can serve as systems biology
      approaches to study the ECM, and then by evaluating pathological protein
      regulatory networks in the liver using systems biology tools. These approaches
      hold great promise for future research.

PMID- 22654993
TI  - Pushing the limits of automatic computational protein design: design, expression,
      and characterization of a large synthetic protein based on a fungal laccase
      scaffold.
AB  - The de novo engineering of new proteins will allow the design of complex systems
      in synthetic biology. But the design of large proteins is very challenging due to
      the large combinatorial sequence space to be explored and the lack of a suitable
      selection system to guide the evolution and optimization. One way to approach
      this challenge is to use computational design methods based on the current
      crystallographic data and on molecular mechanics. We have used a laccase protein
      fold as a scaffold to design a new protein sequence that would adopt a 3D
      conformation in solution similar to a wild-type protein, the Trametes versicolor
      (TvL) fungal laccase. Laccases are multi-copper oxidases that find utility in a
      variety of industrial applications. The laccases with highest activity and redox
      potential are generally secreted fungal glycoproteins. Prokaryotic laccases have
      been identified with some desirable features, but they often exhibit low redox
      potentials. The designed sequence (DLac) shares a 50% sequence identity to the
      original TvL protein. The new DLac gene was overexpressed in E. coli and the
      majority of the protein was found in inclusion bodies. Both soluble protein and
      refolded insoluble protein were purified, and their identity was verified by mass
      spectrometry. Neither protein exhibited the characteristic T1 copper absorbance,
      neither bound copper by atomic absorption, and neither was active using a variety
      of laccase substrates over a range of pH values. Circular dichroism spectroscopy
      studies suggest that the DLac protein adopts a molten globule structure that is
      similar to the denatured and refolded native fungal TvL protein, which is
      significantly different from the natively secreted fungal protein. Taken
      together, these results indicate that the computationally designed DLac expressed
      in E. coli is unable to utilize the same folding pathway that is used in the
      expression of the parent TvL protein or the prokaryotic laccases. This sequence
      can be used going forward to help elucidate the sequence requirements needed for
      prokaryotic multi-copper oxidase expression. ELECTRONIC SUPPLEMENTARY MATERIAL:
      The online version of this article (doi:10.1007/s11693-011-9080-9) contains
      supplementary material, which is available to authorized users.

PMID- 22654995
TI  - Dynamic analysis of the KlGAL regulatory system in Kluyveromyces lactis: a
      comparative study with Saccharomyces cerevisiae.
AB  - The GAL regulatory system is highly conserved in yeast species of Saccharomyces
      cerevisiae and Kluyveromyces lactis. While the GAL system is a well studied
      system in S. cerevisiae, the dynamic behavior of the KlGAL system in K. lactis
      has not been characterized. Here, we have characterized the GAL system in yeast
      K. lactis by developing a dynamic model and comparing its performance to its not
      so-distant cousin S. cerevisiae. The present analysis demonstrates the
      significance of the autoregulatory feedbacks due to KlGal4p, KlGal80p, KlGal1p
      and Lac12p on the dynamic performance of the KlGAL switch. The model predicts the
      experimentally observed absence of bistability in the wild type strain of K.
      lactis, unlike the short term memory of preculturing conditions observed in S.
      cerevisiae. The performance of the GAL switch is distinct for the two yeast
      species although they share similarities in the molecular components. The
      analysis suggests that the whole genome duplication of S. cerevisiae, which
      resulted in a dedicated inducer protein, Gal3p, may be responsible for the high
      sensitivity of the system to galactose concentrations. On the other hand, K.
      lactis uses a bifunctional protein as an inducer in addition to its galactokinase
      activity, which restricts its regulatory role and hence higher galactose levels
      in the medium are needed to trigger the GAL system. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s11693-011-9082-7)
      contains supplementary material, which is available to authorized users.

PMID- 22654996
TI  - Algorithms for optimization of the transport system in living and artificial
      cells.
AB  - An optimization of the transport system in a cell has been considered from the
      viewpoint of the operations research. Algorithms for an optimization of the
      transport system of a cell in terms of both the efficiency and a weak sensitivity
      of a cell to environmental changes have been proposed. The switching of various
      systems of transport is considered as the mechanism of weak sensitivity of a cell
      to changes in environment. The use of the algorithms for an optimization of a
      cardiac cell has been considered by way of example. We received theoretically for
      a cell of a cardiac muscle that at the increase of potassium concentration in the
      environment switching of transport systems for this ion takes place. This
      conclusion qualitatively coincides with experiments. The problem of synthesizing
      an optimal system in an artificial cell has been stated.

PMID- 22654997
TI  - Effect of peppermint oil on serum lipid peroxidation and hepatic enzymes after
      immobility stress in mice.
AB  - This study was undertaken to determine the influences of various doses of
      peppermint oil on the hepatic en-zymes, alanine transaminase, apartate
      tranaminase, alkaline phosphotase and gamma glutamyl transferase and the level of
      malondialdehyde in the serum of mice with and without immobility stress. The mice
      exposed to drink water, 0.9, 27 and 60 mg/kg peppermint oil from the days 1 to 5
      for a period of 4 h before and after immobility stress. Serum MDA in-creased in
      treatment group II, III and IV after immobility stress. There was a significant
      decrease in ALT in treatment group III and IV after immobility stress. There were
      also significant decreases in ALP and GGT in treatment group IV af-ter immobility
      stress. This result may suggest that, MDA level is higher in immobilization
      stress group than in the un-immobilized animals in serum and this results show
      that enzyme activities decreased after immobilization stress.

PMID- 22654998
TI  - Prevalence and control of hypertension in iraqi diabetic patients: a prospective
      cohort study.
AB  - OBJECTIVES: Diabetes and hypertension are major risk factors for cardiovascular
      disease, a leading cause of death in humans. The aim of our study was to
      determine the prevalence of hypertension, and hypertension control among adults
      with diabetes in Basrah (Southern Iraq). METHODS: A prospective cohort study was
      conducted at Al-Faiha Diabetes and Endocrine Center in Basrah. It was started in
      August 2008 to April 2011. The total number of recruited patients with diabetes
      was 5578. RESULTS: Hypertensive diabetic patients constituted 89.6% of this study
      cohort, with 45.3% of them newly discovered in the center. From hypertensive
      patients, 48.2% achieved the target blood pressure of less than 130/80 mmHg. The
      results of the multivariate analyses showed that the factors independently
      associated with the hypertension were aged > 50 years (odds ratio, 0.4; 95% CI,
      0.3 to 0.5; p < 0.001), body mass index equal or more than 25 (odds ratio, 0.5;
      95% CI, 0.4 to 0.6; p < 0.001), insulin use (odds ratio, 0.6; 95% CI, 0.5 to 0.8;
      p < 0.001) and duration of diabetes > 5 years (odds ratio, 0.6; 95% CI, 0.5 to
      0.7; p < 0.001) . CONCLUSION: This study confirmed that hypertension was seen in
      ~90% of diabetic patients in Iraq, and approximately half of them were achieving
      target blood pressure level.

PMID- 22654999
TI  - The effect of exercise on pulpal and gingival blood flow in physically active and
      inactive subjects as assessed by laser Doppler.
AB  - The effects of exercise on pulpal and gingival blood flow are undefined. The
      autonomic nervous system response suggests that they could increase or decrease
      with exercise, and they may be independent of each other. This study attempts to
      answer these questions. MATERIALS AND METHODS: 15 "physically active" subjects
      and 15 "physically inactive" subjects exercised on a treadmill. Laser Doppler
      recordings of pulpal and gingival blood flow were taken before and after
      exercise. RESULTS: There was a mean increase of approximately 50% in both pulpal
      (range -66%-+509%) and gingival (-72%- +1022%) blood flow after exercise, with
      wide variations, with no significant differences between the two groups of
      subjects. CONCLUSION: Exercise could increase pulpal and/or gingival blood flow
      as part of the overall increase in cardiac output with exercise, or could
      decrease pulpal and/or gingival blood flow due to diversion of blood to the
      somatic muscles during exercise. This study suggests that the former
      physiological phenomenon usually takes place at both sites,though there were some
      contradictory results.

PMID- 22655000
TI  - Determinants of Risk Infection During Therapy with Anti TNF-Alpha Blocking Agents
      in Rheumatoid Arthritis.
AB  - The use of TNF-alpha antagonists (infliximab, etanercept, adalimumab) has changed
      the course of many rheumatic diseases including rheumatoid arthritis (RA). Since
      their approval, some questions regarding their safety including infections have
      been observed. The aim of the study was to evaluate the changes in cytokines
      levels and cells subsets in patients with RA during anti TNF blocking agents
      treatment and the possible effect on infections' development. We evaluated in 89
      RA patients [39 treated with etanercept (ETN), 29 with adalimumab (ADA) and 21
      with infliximab (IFN)] at baseline and after 6 months the following parameters:
      procalcitonin, ESR, CRP, cytokines as TNF, IL-6, IL-10, IL-8 and the TNF/IL-10
      ratio, and peripheral mononuclear cells as CD3+, CD3+/CD4+, CD3+/CD8+, CD19+, CD3
      /CD16+/56+, CD14+HLADR+, CD20+, CD19+/CD38+. Peripheral mononuclear cells were
      detected by flow cytometric system Cytomics FC500 and cytokines circulating
      levels by a quantitative sandwich enzyme immunoassay technique (Human IL-8
      Instant ELISAe Bioscience, Human IL-6 Instant ELISA e Bioscience, Human IL-10
      Instant ELISAe Bioscience and Human TNF-a Quantikine immunoassay RD system). A
      lower reduction of CD14+HLADR+ in ADA group 54.6+/-10.4% vs ETA 48.4+/-15.7% vs
      INF 40.7+/-16.5%, p<0.039 was found. No differences in all three groups on
      peripheral mononuclear cells CD3+, CD3+/CD4+, CD3+/CD8+, CD19+, CD 20+,
      CD19+/CD38+, CD3-/CD16+/56+, and cytokine circulating levels were found. The
      number of infections at 6 months was: 10.3% in ADA group, 12.8% in ETN group and
      19.04% in IFN group. A correlation was found between the reduction in CD14+HLADR+
      cells and IFN treatment. Our data showed that the level of CD14+HLADR+ cells was
      reduced during therapy with IFN. ADA and ETN don't reduce lymphocyte populations
      and their subsets such as CD14+HLADR+ cells that play an important role host
      defence.

PMID- 22655001
TI  - Remembering the Chaos - But Life Went on and the Wound Healed. A Four Year Follow
      Up with Parents having had a Baby with Infantile Colic.
AB  - OBJECTIVE: To elucidate parent's experience of having had a baby with colic four
      years previously and of how the colic and care influenced the family in a long
      term perspective. METHODOLOGY AND PARTICIPANTS: A qualitative inductive follow-up
      study with 13 individual and one focus group interview including four parents.
      Altogether ten mothers and seven fathers representing 12 families, who had been
      interviewed when they were in the midst of the colicky period four years ago,
      were in the present study interviewed between December 2010 and May 2011.
      Parents' narratives were analysed using content analysis. RESULTS: Parent's
      memories of the exhausting colic period were vivid, but when the colic had healed
      the family relationships also healed. Although it had taken longer time for some
      parents to attach to their child they now experienced a close relationship with
      their four year old child and felt confident in their role as parent. The colic
      scream was still unbearable and evoked negative feelings in the parents. Parents
      had decreased confidence in Child Health services and made suggestions for
      improvements in the health care approach. Most of all they wished for an
      effective treatment of infantile colic. CONCLUSION: The family relationships were
      healed and the colic left only few residual symptoms but parents still had
      decreased confidence in the Child Health Center. Consequently, there is a need to
      raise awareness to parents' situation when having a child with infantile colic.

PMID- 22655002
TI  - Registered Nurses' View of Performing Pain Assessment among Persons with Dementia
      as Consultant Advisors.
AB  - BACKGROUND: Pain assessment in persons with dementia is well known as a
      challenging issue to professional caregivers, because of these patients'
      difficulties in verbalising pain problems. Within municipal dementia care in
      Sweden, pain assessment has become problematic for registered nurses, as they
      have entered a new role in their nursing profession, from being clinical
      practitioners to becoming consultant advisers to other health care staff. AIM: To
      present municipal registered nurses' view of pain assessment in persons with
      dementia in relation to their nursing profession as consultant advisers. METHODS:
      Purposive sampling was undertaken with 11 nurses invited to participate. Data
      were collected by focus groups. Qualitative content analysis was used to analyse
      the data. FINDINGS: Four categories were identified to describe registered
      nurses' view of pain assessment: estrangement from practical nursing care, time
      consuming and unsafe pain documentation, unfulfilled needs of reflection
      possibilities, and collaboration and coordination. CONCLUSIONS: The performance
      of pain assessment through a consultant advising function is experienced as
      frustrating and as an uncomfortable nursing situation. The nurses feel resistance
      to providing nursing in this way. They view nursing as a clinical task demanding
      daily presence among patients to enable them to make accurate and safe
      assessments. However, due to the consultative model, setting aside enough time
      for the presence seems difficult to accomplish. It is necessary to promote the
      quality of systematic routines in pain assessment and reflection, as well as
      developing professional knowledge of how pain can be expressed by dementia
      patients, especially those with communication difficulties.

PMID- 22655004
TI  - Preface to special topic: multiphase microfluidics.

PMID- 22655003
TI  - Biosensors for immune cell analysis-A perspective.
AB  - Massively parallel analysis of single immune cells or small immune cell colonies
      for disease detection, drug screening, and antibody production represents a
      "killer app" for the rapidly maturing microfabrication and microfluidic
      technologies. In our view, microfabricated solid-phase and flow cytometry
      platforms of the future will be complete with biosensors and
      electrical/mechanical/optical actuators and will enable multi-parametric analysis
      of cell function, real-time detection of secreted signals, and facile retrieval
      of cells deemed interesting.

PMID- 22655005
TI  - Calcium carbonate polymorph control using droplet-based microfluidics.
AB  - Calcium carbonate (CaCO(3)) is one of the most abundant minerals and of high
      importance in many areas of science including global CO(2) exchange, industrial
      water treatment energy storage, and the formation of shells and skeletons.
      Industrially, calcium carbonate is also used in the production of cement,
      glasses, paints, plastics, rubbers, ceramics, and steel, as well as being a key
      material in oil refining and iron ore purification. CaCO(3) displays a complex
      polymorphic behaviour which, despite numerous experiments, remains poorly
      characterised. In this paper, we report the use of a segmented-flow microfluidic
      reactor for the controlled precipitation of calcium carbonate and compare the
      resulting crystal properties with those obtained using both continuous flow
      microfluidic reactors and conventional bulk methods. Through combination of equal
      volumes of equimolar aqueous solutions of calcium chloride and sodium carbonate
      on the picoliter scale, it was possible to achieve excellent definition of both
      crystal size and size distribution. Furthermore, highly reproducible control over
      crystal polymorph could be realised, such that pure calcite, pure vaterite, or a
      mixture of calcite and vaterite could be precipitated depending on the reaction
      conditions and droplet-volumes employed. In contrast, the crystals precipitated
      in the continuous flow and bulk systems comprised of a mixture of calcite and
      vaterite and exhibited a broad distribution of sizes for all reaction conditions
      investigated.

PMID- 22655006
TI  - CO(2) dissolution in water using long serpentine microchannels.
AB  - The evolution of carbon dioxide bubbles dissolving in water is experimentally
      examined using long microchannels. We study the coupling between bubble
      hydrodynamics and dissolution in confined geometries. The gas impregnation
      process in liquid produces significant flow rearrangements. Depending on the
      initial volumetric liquid fraction, three operating regimes are identified,
      namely saturating, coalescing, and dissolving. The morphological and dynamical
      transition from segmented to dilute bubbly flows is investigated. Tracking
      individual bubbles along the flow direction is used to calculate the temporal
      evolution of the liquid volumetric fraction and the average flow velocity near
      reference bubbles over long distances. This method allows us to empirically
      establish the functional relationship between bubble size and velocity. Finally,
      we examine the implication of this relationship during the coalescing flow
      regime, which limits the efficiency of the dissolution process.

PMID- 22655007
TI  - Droplet dispensing in digital microfluidic devices: Assessment of long-term
      reproducibility.
AB  - We report an in-depth study of the long-term reproducibility and reliability of
      droplet dispensing in digital microfluidic devices (DMF). This involved
      dispensing droplets from a reservoir, measuring the volume of both the droplet
      and the reservoir droplet and then returning the daughter droplet to the original
      reservoir. The repetition of this process over the course of several hundred
      iterations offers, for the first time, a long-term view of droplet dispensing in
      DMF devices. Results indicate that the ratio between the spacer thickness and the
      electrode size influences the reliability of droplet dispensing. In addition,
      when the separation between the plates is large, the volume of the reservoir
      greatly affects the reproducibility in the volume of the dispensed droplets,
      creating "reliability regimes." We conclude that droplet dispensing exhibits
      superior reliability as inter-plate device spacing is decreased, and the daughter
      droplet volume is most consistent when the reservoir volume matches that of the
      reservoir electrode.

PMID- 22655008
TI  - Tuning bubbly structures in microchannels.
AB  - Foams have many useful applications that arise from the structure and size
      distribution of the bubbles within them. Microfluidics allows for the rapid
      formation of uniform bubbles, where bubble size and volume fraction are functions
      of the input gas pressure, liquid flow rate, and device geometry. After
      formation, the microchannel confines the bubbles and determines the resulting
      foam structure. Bubbly structures can vary from a single row ("dripping"), to
      multiple rows ("alternating"), to densely packed bubbles ("bamboo" and dry
      foams). We show that each configuration arises in a distinct region of the
      operating space defined by bubble volume and volume fraction. We describe the
      boundaries between these regions using geometric arguments and show that the
      boundaries are functions of the channel aspect ratio. We compare these geometric
      arguments with foam structures observed in experiments using flow-focusing, T
      junction, and co-flow designs to generate stable nitrogen bubbles in aqueous
      surfactant solution and stable droplets in oil containing dissolved surfactant.
      The outcome of this work is a set of design parameters that can be used to
      achieve desired foam structures as a function of device geometry and experimental
      control parameters.

PMID- 22655009
TI  - Tunable spatial heterogeneity in structure and composition within aqueous
      microfluidic droplets.
AB  - In this paper, we demonstrate biphasic microfluidic droplets with broadly tunable
      internal structures, from simple near-equilibrium drop-in-drop morphologies to
      complex yet uniform non-equilibrium steady-state structures. The droplets contain
      an aqueous mixture of poly(ethylene glycol) (PEG) and dextran and are dispensed
      into an immiscible oil in a microfluidic T-junction device. Above a certain well
      defined threshold droplet speed, the inner dextran-rich phase is "stirred" within
      the outer PEG-rich phase. The stirred polymer mixture is observed to exhibit a
      near continuum of speed and composition-dependent phase morphologies. There is
      increasing interest in the use of such aqueous two-phase systems in microfluidic
      devices for biomolecular applications in a variety of contexts. Our work presents
      a method to go beyond equilibrium phase morphologies in generating microfluidic
      "multiple" emulsions and at the same time raises the possibility of biochemical
      experimentation in benign yet complex biomimetic milieus.

PMID- 22655010
TI  - Utilizing microfluidics to synthesize polyethylene glycol microbeads for Forster
      resonance energy transfer based glucose sensing.
AB  - Here, we utilize microfluidic droplet technology to generate photopolymerizeable
      polyethylene glycol (PEG) hydrogel microbeads incorporating a fluorescence-based
      glucose bioassay. A microfluidic T-junction and multiphase flow of fluorescein
      isothiocyanate dextran, tetramethyl rhodamine isothiocyanate concanavalin A, and
      PEG in water were used to generate microdroplets in a continuous stream of
      hexadecane. The microdroplets were photopolymerized mid-stream with ultraviolet
      light exposure to form PEG microbeads and were collected at the outlet for
      further analysis. Devices were prototyped in PDMS and generated highly
      monodisperse 72 +/- 2 MUm sized microbeads (measured after transfer into aqueous
      phase) at a continuous flow rate between 0.04 ml/h-0.06 ml/h. Scanning electron
      microscopy analysis was conducted to analyze and confirm microbead integrity and
      surface morphology. Glucose sensing was carried out using a Forster resonance
      energy transfer (FRET) based assay. A proportional fluorescence intensity
      increase was measured within a 1-10 mM glucose concentration range.
      Microfluidically synthesized microbeads encapsulating sensing biomolecules offer
      a quick and low cost method to generate monodisperse biosensors for a variety of
      applications including cell cultures systems, tissue engineering, etc.

PMID- 22655011
TI  - Field-free particle focusing in microfluidic plugs.
AB  - Particle concentration is a key unit operation in biochemical assays. Although
      there are many techniques for particle concentration in continuous-phase
      microfluidics, relatively few are available in multiphase (plug-based)
      microfluidics. Existing approaches generally require external electric or
      magnetic fields together with charged or magnetized particles. This paper reports
      a passive technique for particle concentration in water-in-oil plugs which relies
      on the interaction between particle sedimentation and the recirculating vortices
      inherent to plug flow in a cylindrical capillary. This interaction can be
      quantified using the Shields parameter ([Formula: see text]), a dimensionless
      ratio of a particle's drag force to its gravitational force, which scales with
      plug velocity. Three regimes of particle behavior are identified. When [Formula:
      see text] is less than the movement threshold (region I), particles sediment to
      the bottom of the plug where the internal vortices subsequently concentrate the
      particles at the rear of the plug. We demonstrate highly efficient concentration
      (~100%) of 38 MUm glass beads in 500 MUm diameter plugs traveling at velocities
      up to 5 mm/s. As [Formula: see text] is increased beyond the movement threshold
      (region II), particles are suspended in well-defined circulation zones which
      begin at the rear of the plug. The length of the zone scales linearly with plug
      velocity, and at sufficiently large [Formula: see text], it spans the length of
      the plug (region III). A second effect, attributed to the co-rotating vortices at
      the rear cap, causes particle aggregation in the cap, regardless of flow
      velocity. Region I is useful for concentrating/collecting particles, while the
      latter two are useful for mixing the beads with the solution. Therefore, the two
      key steps of a bead-based assay, concentration and resuspension, can be achieved
      simply by changing the plug velocity. By exploiting an interaction of
      sedimentation and recirculation unique to multiphase flow, this simple technique
      achieves particle concentration without on-chip components, and could therefore
      be applied to a range of heterogeneous screening assays in discrete nl plugs.

PMID- 22655012
TI  - Vimentin networks at tunable ion-concentration in microfluidic drops.
AB  - The structure and function of biological systems, for example, cells and
      proteins, depend strongly on their chemical environment. To investigate such
      dependence, we design a polydimethylsiloxane-based microfluidic device to
      encapsulate biological systems in picoliter-sized drops. The content of each
      individual drop is tuned in a defined manner. As a key feature of our method, the
      individual chemical composition is determined and related to the drop content. In
      our case, the drop content is imaged using microscopy methods, while the drops
      are immobilized to allow for long-time studies. As an application of our device,
      we study the influence of divalent ions on vimentin intermediate filament
      networks in a quantitative way by tuning the magnesium concentration from drop to
      drop. This way we are able to directly image the effect of magnesium on the
      fluorescently tagged protein in a few hundreds of drops. Our study shows that
      with increasing magnesium concentration in the drops, the compaction of the
      networks becomes more pronounced. The degree of compaction is characterized by
      different morphologies; freely fluctuating networks are observed at comparatively
      low magnesium concentrations of 5-10 mM, while with increasing magnesium
      concentration reaching 16 mM they develop into fully aggregated networks. Our
      approach demonstrates how a systematic study of interactions in biological
      systems can benefit from the exceptional controllability of microfluidic methods.

PMID- 22655013
TI  - Formation of embryoid bodies using dielectrophoresis.
AB  - Embryoid body (EB) formation forms an important step in embryonic stem cell
      differentiation invivo. In murine embryonic stem cell (mESC) cultures EB
      formation is inhibited by the inclusion of leukaemic inhibitory factor (LIF) in
      the medium. Assembly of mESCs into aggregates by positive dielectrophoresis (DEP)
      in high field regions between interdigitated oppositely castellated electrodes
      was found to initiate EB formation. Embryoid body formation in aggregates formed
      with DEP occurred at a more rapid rate-in fact faster compared to conventional
      methods-in medium without LIF. However, EB formation also occurred in medium in
      which LIF was present when the cells were aggregated with DEP. The optimum
      characteristic size for the electrodes for EB formation with DEP was found to be
      75-100 microns; aggregates smaller than this tended to merge, whilst aggregates
      larger than this tended to split to form multiple EBs. Experiments with ESCs in
      which green fluorescent protein (GFP) production was targeted to the mesodermal
      gene brachyury indicated that differentiation within embryoid bodies of this size
      may preferentially occur along the mesoderm lineage. As hematopoietic lineages
      during normal development derive from mesoderm, the finding points to a possible
      application of DEP formed EBs in the production of blood-based products from
      ESCs.

PMID- 22655014
TI  - New rationale for large metazoan embryo manipulations on chip-based devices.
AB  - The lack of technologies that combine automated manipulation, sorting, as well as
      immobilization of single metazoan embryos remains the key obstacle to high
      throughput organism-based ecotoxicological analysis and drug screening routines.
      Noticeably, the major obstacle hampering the automated trapping and arraying of
      millimetre-sized embryos on chip-based devices is their substantial size and
      mass, which lead to rapid gravitational-induced sedimentation and strong inertial
      forces. In this work, we present a comprehensive mechanistic and design rationale
      for manipulation and passive trapping of individual zebrafish embryos using only
      hydrodynamic forces. We provide evidence that by employing innovative design
      features, highly efficient hydrodynamic positioning of large embryos on a chip
      can be achieved. We also show how computational fluid dynamics-guided design and
      the Lagrangian particle tracking modeling can be used to optimize the chip
      performance. Importantly, we show that rapid prototyping and medium scale
      fabrication of miniaturized devices can be greatly accelerated by combining high
      speed laser prototyping with replica moulding in poly(dimethylsiloxane) instead
      of conventional photolithography techniques. Our work establishes a new paradigm
      for chip-based manipulation of large multicellular organisms with diameters well
      above 1 mm and masses often exceeding 1 mg. Passive docking of large embryos is
      an attractive alternative to provide high level of automation while alleviating
      potentially deleterious effects associated with the use of active chip actuation.
      This greatly expands the capabilities of bioanalyses performed on small model
      organisms and offers numerous and currently inaccessible laboratory automation
      advantages.

PMID- 22655015
TI  - Novel on-demand droplet generation for selective fluid sample extraction.
AB  - A novel microfluidic device enabling selective generation of droplets and
      encapsulation of targets is presented. Unlike conventional methods, the presented
      mechanism generates droplets with unique selectivity by utilizing a K-junction
      design. The K-junction is a modified version of the classic T-junction with an
      added leg that serves as the exit channel for waste. The dispersed phase fluid
      enters from one diagonal of the K and exits the other diagonal while the
      continuous phase travels in the straight leg of the K. The intersection forms an
      interface that allows the dispersed phase to be controllably injected through
      actuation of an elastomer membrane located above the inlet channel near the
      interface. We have characterized two critical components in controlling the
      droplet size-membrane actuation pressure and timing as well as identified the
      region of fluid in which the droplet will be formed. This scheme will have
      applications in fluid sampling processes and selective encapsulation of
      materials. Selective encapsulation of a single cell from the dispersed phase
      fluid is demonstrated as an example of functionality of this design.

PMID- 22655016
TI  - Microfluidics based on ZnO/nanocrystalline diamond surface acoustic wave devices.
AB  - Surface acoustic wave (SAW) devices with 64 MUm wavelength were fabricated on a
      zinc oxide (ZnO) film deposited on top of an ultra-smooth nanocrystalline diamond
      (UNCD) layer. The smooth surface of the UNCD film allowed the growth of the ZnO
      film with excellent c-axis orientation and low surface roughness, suitable for
      SAW fabrication, and could restrain the wave from significantly dissipating into
      the substrate. The frequency response of the fabricated devices was characterized
      and a Rayleigh mode was observed at ~65.4 MHz. This mode was utilised to
      demonstrate that the ZnO/UNCD SAW device can be successfully used for
      microfluidic applications. Streaming, pumping, and jetting using microdroplets of
      0.5 and 20 MUl were achieved and characterized under different powers applied to
      the SAW device, focusing more on the jetting behaviors induced by the ZnO SAW.

PMID- 22655017
TI  - A microfluidic platform for controlled biochemical stimulation of twin neuronal
      networks.
AB  - Spatially and temporally resolved delivery of soluble factors is a key feature
      for pharmacological applications. In this framework, microfluidics coupled to
      multisite electrophysiology offers great advantages in neuropharmacology and
      toxicology. In this work, a microfluidic device for biochemical stimulation of
      neuronal networks was developed. A micro-chamber for cell culturing, previously
      developed and tested for long term neuronal growth by our group, was provided
      with a thin wall, which partially divided the cell culture region in two sub
      compartments. The device was reversibly coupled to a flat micro electrode array
      and used to culture primary neurons in the same microenvironment. We demonstrated
      that the two fluidically connected compartments were able to originate two
      parallel neuronal networks with similar electrophysiological activity but
      functionally independent. Furthermore, the device allowed to connect the outlet
      port to a syringe pump and to transform the static culture chamber in a perfused
      one. At 14 days invitro, sub-networks were independently stimulated with a test
      molecule, tetrodotoxin, a neurotoxin known to block action potentials, by means
      of continuous delivery. Electrical activity recordings proved the ability of the
      device configuration to selectively stimulate each neuronal network individually.
      The proposed microfluidic approach represents an innovative methodology to
      perform biological, pharmacological, and electrophysiological experiments on
      neuronal networks. Indeed, it allows for controlled delivery of substances to
      cells, and it overcomes the limitations due to standard drug stimulation
      techniques. Finally, the twin network configuration reduces biological
      variability, which has important outcomes on pharmacological and drug screening.

PMID- 22655018
TI  - Construction and operation of a microrobot based on magnetotactic bacteria in a
      microfluidic chip.
AB  - Magnetotactic bacteria (MTB) are capable of swimming along magnetic field lines.
      This unique feature renders them suitable in the development of magnetic-guided,
      auto-propelled microrobots to serve in target molecule separation and detection,
      drug delivery, or target cell screening in a microfluidic chip. The biotechnology
      to couple these bacteria with functional loads to form microrobots is the
      critical point in its application. Although an immunoreaction approach to attach
      functional loads to intact MTB was suggested, details on its realization were
      hardly mentioned. In the current paper, MTB-microrobots were constructed by
      attaching 2 MUm diameter microbeads to marine magnetotactic ovoid MO-1 cells
      through immunoreactions. These microrobots were controlled using a special
      control and tracking system. Experimental results prove that the attachment
      efficiency can be improved to ~30% via an immunoreaction. The motility of the
      bacteria attached with different number of loads was also assessed. The results
      show that MTB can transport one load at a velocity of ~21 MUm/s and still move
      and survive for over 30 min. The control and tracking system is fully capable of
      directing and monitoring the movement of the MTB-microrobots. The rotating
      magnetic fields can stop the microrobots by trapping them as they swim within a
      circular field with a controllable size. The system has potential use in chemical
      analyses and medical diagnoses using biochips as well as in nano/microscale
      transport.

PMID- 22655019
TI  - High-performance microfluidic rectifier based on sudden expansion channel with
      embedded block structure.
AB  - A high-performance microfluidic rectifier incorporating a microchannel and a
      sudden expansion channel is proposed. In the proposed device, a block structure
      embedded within the expansion channel is used to induce two vortex structures at
      the end of the microchannel under reverse flow conditions. The vortices reduce
      the hydraulic diameter of the microchannel and, therefore, increase the flow
      resistance. The rectification performance of the proposed device is evaluated by
      both experimentally and numerically. The experimental and numerical values of the
      rectification performance index (i.e., the diodicity, Di) are found to be 1.54
      and 1.76, respectively. Significantly, flow rectification is achieved without the
      need for moving parts. Thus, the proposed device is ideally suited to the high
      pressure environment characteristic of most micro-electro-mechanical-systems
      (MEMS)-based devices. Moreover, the rectification performance of the proposed
      device is superior to that of existing valveless rectifiers based on Tesla
      valves, simple nozzle/diffuser structures, or cascaded nozzle/diffuser
      structures.

PMID- 22655020
TI  - Microstripes for transport and separation of magnetic particles.
AB  - We present a simple technique for creating an on-chip magnetic particle conveyor
      based on exchange-biased permalloy microstripes. The particle transportation
      relies on an array of stripes with a spacing smaller than their width in
      conjunction with a periodic sequence of four different externally applied
      magnetic fields. We demonstrate the controlled transportation of a large
      population of particles over several millimeters of distance as well as the
      spatial separation of two populations of magnetic particles with different
      magnetophoretic mobilities. The technique can be used for the controlled
      selective manipulation and separation of magnetically labelled species.

PMID- 22655021
TI  - Geometrical effects in microfluidic-based microarrays for rapid, efficient single
      cell capture of mammalian stem cells and plant cells.
AB  - In this paper, a detailed numerical and experimental investigation into the
      optimisation of hydrodynamic micro-trapping arrays for high-throughput capture of
      single polystyrene (PS) microparticles and three different types of live cells at
      trapping times of 30 min or less is described. Four different trap geometries
      (triangular, square, conical, and elliptical) were investigated within three
      different device generations, in which device architecture, channel geometry,
      inter-trap spacing, trap size, and trap density were varied. Numerical simulation
      confirmed that (1) the calculated device dimensions permitted partitioned flow
      between the main channel and the trap channel, and further, preferential flow
      through the trap channel in the absence of any obstruction; (2) different trap
      shapes, all having the same dimensional parameters in terms of depth, trapping
      channel lengths and widths, main channel lengths and widths, produce contrasting
      streamline plots and that the interaction of the fluid with the different
      geometries can produce areas of stagnated flow or distorted field lines; and (3)
      that once trapped, any motion of the trapped particle or cell or a shift in its
      configuration within the trap can result in significant increases in pressures on
      the cell surface and variations in the shear stress distribution across the
      cell's surface. Numerical outcomes were then validated experimentally in terms of
      the impact of these variations in device design elements on the percent occupancy
      of the trapping array (with one or more particles or cells) within these targeted
      short timeframes. Limitations on obtaining high trap occupancies in the devices
      were shown to be primarily a result of particle aggregation, channel clogging and
      the trap aperture size. These limitations could be overcome somewhat by
      optimisation of these device design elements and other operational variables,
      such as the average carrier fluid velocity. For example, for the 20 MUm
      polystyrene microparticles, the number of filled traps increased from 32% to 42%
      during 5-10 min experiments in devices with smaller apertures. Similarly, a 40%
      60% reduction in trapping channel size resulted in an increase in the amount of
      filled traps, from 0% to almost 90% in 10 min, for the human bone marrow derived
      mesenchymal stem cells, and 15%-85% in 15 min for the human embryonic stem cells.
      Last, a reduction of the average carrier fluid velocity by 50% resulted in an
      increase from 80% to 92% occupancy of single algae cells in traps. Interestingly,
      changes in the physical properties of the species being trapped also had a
      substantial impact, as regardless of the trap shape, higher percent occupancies
      were observed with cells compared to single PS microparticles in the same device,
      even though they are of approximately the same size. This investigation showed
      that in microfluidic single cell capture arrays, the trap shape that maximizes
      cell viability is not necessarily the most efficient for high-speed single cell
      capture. However, high-speed trapping configurations for delicate mammalian cells
      are possible but must be optimised for each cell type and designed principally in
      accordance with the trap size to cell size ratio.

PMID- 22655022
TI  - Flow biosensing and sampling in indirect electrochemical detection.
AB  - Miniaturization in biological analyses has several advantages, such as sample
      volume reduction and fast response time. The integration of miniaturized
      biosensors within lab-on-a-chip setups under flow conditions is highly desirable,
      not only because it simplifies process handling but also because measurements
      become more robust and operator-independent. In this work, we study the
      integration of flow amperometric biosensors within a microfluidic platform when
      analyte concentration is indirectly measured. As a case study, we used a platinum
      miniaturized glucose biosensor, where glucose is enzymatically converted to
      [Formula: see text] that is oxidized at the electrode. The experimental results
      produced are strongly coupled to a theoretical analysis of fluid dynamic
      conditions affecting the electrochemical response of the sensor. We verified that
      the choice of the inlet flow rate is a critical parameter in flow biosensors,
      because it affects both glucose and [Formula: see text] transport, to and from
      the electrode. We identify optimal flow rate conditions for accurate sensing at
      high time resolution. A dimensionless theoretical analysis allows the extension
      of the results to other sensing systems according to fluid dynamic similarity
      principles. Furthermore, we developed a microfluidic design that connects a
      sampling unit to the biosensor, in order to decouple the sampling flow rate from
      that of the actual measurement.

PMID- 22655023
TI  - A microfluidics approach towards high-throughput pathogen removal from blood
      using margination.
AB  - Sepsis is an adverse systemic inflammatory response caused by microbial infection
      in blood. This paper reports a simple microfluidic approach for intrinsic, non
      specific removal of both microbes and inflammatory cellular components (platelets
      and leukocytes) from whole blood, inspired by the invivo phenomenon of leukocyte
      margination. As blood flows through a narrow microchannel (20 * 20 um),
      deformable red blood cells (RBCs) migrate axially to the channel centre,
      resulting in margination of other cell types (bacteria, platelets, and
      leukocytes) towards the channel sides. By using a simple cascaded channel design,
      the blood samples undergo a 2-stage bacteria removal in a single pass through the
      device, thereby allowing higher bacterial removal efficiency. As an application
      for sepsis treatment, we demonstrated separation of Escherichia coli and
      Saccharomyces cerevisiae spiked into whole blood, achieving high removal
      efficiencies of ~80% and ~90%, respectively. Inflammatory cellular components
      were also depleted by >80% in the filtered blood samples which could help to
      modulate the host inflammatory response and potentially serve as a blood
      cleansing method for sepsis treatment. The developed technique offers significant
      advantages including high throughput (~1 ml/h per channel) and label-free
      separation which allows non-specific removal of any blood-borne pathogens
      (bacteria and fungi). The continuous processing and collection mode could
      potentially enable the return of filtered blood back to the patient directly,
      similar to a simple and complete dialysis circuit setup. Lastly, we designed and
      tested a larger filtration device consisting of 6 channels in parallel (~6 ml/h)
      and obtained similar filtration performances. Further multiplexing is possible by
      increasing channel parallelization or device stacking to achieve higher
      throughput comparable to convectional blood dialysis systems used in clinical
      settings.

PMID- 22655024
TI  - Manipulating single annealed polyelectrolyte under alternating current electric
      fields: Collapse versus accumulation.
AB  - Effective manipulation and understanding of the structural and dynamic behaviors
      of a single polyelectrolyte (PE) under alternating current (AC) electric fields
      are of great scientific and technological importance because of its intimate
      relevance to emerging bionanotechnology. In this work, we employ fluorescence
      correlation spectroscopy (FCS) to study the conformational and AC-electrokinetic
      behaviors of a model annealed PE, poly(2-vinyl pyridine) (P2VP) under both
      spatially uniform and non-uniform AC fields at a single molecule level. Under
      spatially uniform AC-fields, we observe a gradual and continuous coil-to-globule
      conformational transition (CGT) of single P2VP at varied AC-frequency when a
      critical AC-field strength is exceeded, in contrast to the pH-induced abrupt CGT
      in the absence of AC-fields. On the contrary, under spatially non-uniform AC
      fields, we observe field-driven net flow and accumulation of P2VP near high AC
      field regions due to combined AC electro-osmosis and dielectrophoresis but
      surprisingly no conformational change. Thus, distinct AC-electric polarization
      effect on single annealed PE subject to AC-field homogeneity is suggested.

PMID- 22655025
TI  - Electronic detection of dielectrophoretic forces exerted on particles flowing
      over interdigitated electrodes.
AB  - Dielectric particles flowing through a microfluidic channel over a set of
      coplanar electrodes can be simultaneously capacitively detected and
      dielectrophoretically (DEP) actuated when the high (1.45 GHz) and low (100 kHz-20
      MHz) frequency electromagnetic fields are concurrently applied through the same
      set of electrodes. Assuming a simple model in which the only forces acting upon
      the particles are apparent gravity, hydrodynamic lift, DEP force, and fluid drag,
      actuated particle trajectories can be obtained as numerical solutions of the
      equations of motion. Numerically calculated changes of particle elevations
      resulting from the actuation simulated in this way agree with the corresponding
      elevation changes estimated from the electronic signatures generated by the
      experimentally actuated particles. This verifies the model and confirms the
      correlation between the DEP force and the electronic signature profile. It
      follows that the electronic signatures can be used to quantify the actuation that
      the dielectric particle experiences as it traverses the electrode region. Using
      this principle, particles with different dielectric properties can be effectively
      identified based exclusively on their signature profile. This approach was used
      to differentiate viable from non-viable yeast cells (Saccharomyces cerevisiae).

PMID- 22655026
TI  - Uniform yeast cell assembly via microfluidics.
AB  - This paper reports the use of microfluidic approaches for the fabrication of
      yeastosomes (yeast-celloidosomes) based on self-assembly of yeast cells onto
      liquid-solid or liquid-gas interfaces. Precise control over fluidic flows in
      droplet- and bubble-forming microfluidic devices allows production of
      monodispersed, size-selected templates. The general strategy to organize and
      assemble living cells is to tune electrostatic attractions between the template
      (gel or gas core) and the cells via surface charging. Layer-by-Layer (LbL)
      polyelectrolyte deposition was employed to invert or enhance charges of solid
      surfaces. We demonstrated the ability to produce high-quality, monolayer-shelled
      yeastosome structures under proper conditions when sufficient electrostatic
      driving forces are present. The combination of microfluidic fabrication with cell
      self-assembly enables a versatile platform for designing synthetic hierarchy bio
      structures.

PMID- 22655027
TI  - Loss of CCDC6, the first identified RET partner gene, affects pH2AX S139 levels
      and accelerates mitotic entry upon DNA damage.
AB  - CCDC6 was originally identified in chimeric genes caused by chromosomal
      translocation involving the RET proto-oncogene in some thryoid tumors mostly upon
      ionizing radiation exposure. Recognised as a pro-apoptotic phosphoprotein that
      negatively regulates CREB1-dependent transcription, CCDC6 is an ATM substrate
      that is responsive to genotoxic stress. Here we report that following genotoxic
      stress, loss or inactivation of CCDC6 in cancers that carry the CCDC6 fusion,
      accelerates the dephosphorylation of pH2AX S139, resulting in defective G2 arrest
      and premature mitotic entry. Moreover, we show that CCDC6 depleted cells appear
      to repair DNA damaged in a shorter time compared to controls, based on reporter
      assays in cells. High-troughput proteomic screening predicted the interaction
      between the CCDC6 gene product and the catalytic subunit of Serin-Threonin
      Protein Phosphatase 4 (PP4c) recently identified as the evolutionarily conserved
      pH2AX S139 phosphatase that is activated upon DNA Damage. We describe the
      interaction between CCDC6 and PP4c and we report the modulation of PP4c enzymatic
      activity in CCDC6 depleted cells. We discuss the functional significance of CCDC6
      PP4c interactions and hypothesize that CCDC6 may act in the DNA Damage Response
      by negatively modulating PP4c activity. Overall, our data suggest that in primary
      tumours the loss of CCDC6 function could influence genome stability and thereby
      contribute to carcinogenesis.

PMID- 22655028
TI  - Regulation of signaling at regions of cell-cell contact by endoplasmic reticulum
      bound protein-tyrosine phosphatase 1B.
AB  - Protein-tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed PTP that is
      anchored to the endoplasmic reticulum (ER). PTP1B dephosphorylates activated
      receptor tyrosine kinases after endocytosis, as they transit past the ER.
      However, PTP1B also can access some plasma membrane (PM)-bound substrates at
      points of cell-cell contact. To explore how PTP1B interacts with such substrates,
      we utilized quantitative cellular imaging approaches and mathematical modeling of
      protein mobility. We find that the ER network comes in close proximity to the PM
      at apparently specialized regions of cell-cell contact, enabling PTP1B to engage
      substrate(s) at these sites. Studies using PTP1B mutants show that the ER anchor
      plays an important role in restricting its interactions with PM substrates mainly
      to regions of cell-cell contact. In addition, treatment with PTP1B inhibitor
      leads to increased tyrosine phosphorylation of EphA2, a PTP1B substrate,
      specifically at regions of cell-cell contact. Collectively, our results identify
      PM-proximal sub-regions of the ER as important sites of cellular signaling
      regulation by PTP1B.

PMID- 22655029
TI  - Loss of MHC and neutral variation in Peary caribou: genetic drift is not
      mitigated by balancing selection or exacerbated by MHC allele distributions.
AB  - Theory and empirical results suggest that the rate of loss of variation at Mhc
      and neutral microsatellite loci may differ because selection influences Mhc
      genes, and because a high proportion of rare alleles at Mhc loci may result in
      high rates of loss via drift. Most published studies compare Mhc and
      microsatellite variation in various contemporary populations to infer the effects
      of population size on genetic variation, even though different populations are
      likely to have different demographic histories that may also affect contemporary
      genetic variation. We directly compared loss of variation at Mhc and
      microsatellite loci in Peary caribou by comparing historical and contemporary
      samples. We observed that similar proportions of genetic variation were lost over
      time at each type of marker despite strong evidence for selection at Mhc genes.
      These results suggest that microsatellites can be used to estimate genome-wide
      levels of variation, but also that adaptive potential is likely to be lost
      following population bottlenecks. However, gene conversion and recombination at
      Mhc loci may act to increase variation following bottlenecks.

PMID- 22655030
TI  - Thermodynamics of aryl-dihydroxyphenyl-thiadiazole binding to human Hsp90.
AB  - The design of specific inhibitors against the Hsp90 chaperone and other enzyme
      relies on the detailed and correct understanding of both the thermodynamics of
      inhibitor binding and the structural features of the protein-inhibitor complex.
      Here we present a detailed thermodynamic study of binding of aryl-dihydroxyphenyl
      thiadiazole inhibitor series to recombinant human Hsp90 alpha isozyme. The
      inhibitors are highly potent, with the intrinsic K(d) approximately equal to 1 nM
      as determined by isothermal titration calorimetry (ITC) and thermal shift assay
      (TSA). Dissection of protonation contributions yielded the intrinsic
      thermodynamic parameters of binding, such as enthalpy, entropy, Gibbs free
      energy, and the heat capacity. The differences in binding thermodynamic
      parameters between the series of inhibitors revealed contributions of the
      functional groups, thus providing insight into molecular reasons for improved or
      diminished binding efficiency. The inhibitor binding to Hsp90 alpha primarily
      depended on a large favorable enthalpic contribution combined with the smaller
      favorable entropic contribution, thus suggesting that their binding was both
      enthalpically and entropically optimized. The enthalpy-entropy compensation
      phenomenon was highly evident when comparing the inhibitor binding enthalpies and
      entropies. This study illustrates how detailed thermodynamic analysis helps to
      understand energetic reasons for the binding efficiency and develop more potent
      inhibitors that could be applied for therapeutic use as Hsp90 inhibitors.

PMID- 22655031
TI  - Comparison of storage conditions for human vaginal microbiome studies.
AB  - BACKGROUND: The effect of storage conditions on the microbiome and metabolite
      composition of human biological samples has not been thoroughly investigated as a
      potential source of bias. We evaluated the effect of two common storage
      conditions used in clinical trials on the bacterial and metabolite composition of
      the vaginal microbiota using pyrosequencing of barcoded 16S rRNA gene sequencing
      and (1)H-NMR analyses. METHODOLOGY/PRINCIPAL FINDINGS: Eight women were enrolled
      and four mid-vaginal swabs were collected by a physician from each woman. The
      samples were either processed immediately, stored at -80 degrees C for 4 weeks or
      at -20 degrees C for 1 week followed by transfer to -80 degrees C for another 4
      weeks prior to analysis. Statistical methods, including Kolmogorovo-Smirnov and
      Wilcoxon tests, were performed to evaluate the differences in vaginal bacterial
      community composition and metabolites between samples stored under different
      conditions. The results showed that there were no significant differences between
      samples processed immediately after collection or stored for varying durations.
      (1)H-NMR analysis of the small molecule metabolites in vaginal secretions
      indicated that high levels of lactic acid were associated with Lactobacillus
      dominated communities. Relative abundance of lactic acid did not appear to
      correlate with relative abundance of individual Lactobacillus sp. in this limited
      sample, although lower levels of lactic acid were observed when L. gasseri was
      dominant, indicating differences in metabolic output of seemingly similar
      communities. CONCLUSIONS/SIGNIFICANCE: These findings benefit large-scale, field
      based microbiome and metabolomic studies of the vaginal microbiota.

PMID- 22655032
TI  - Reduced sensitivity to immediate reward during decision-making in older than
      younger adults.
AB  - We examined whether older adults differ from younger adults in the degree to
      which they favor immediate over delayed rewards during decision-making. To
      examine the neural correlates of age-related differences in delay discounting we
      acquired functional MR images while participants made decisions between smaller
      but sooner and larger but later monetary rewards. The behavioral results show age
      related reductions in delay discounting. Less impulsive decision-making in older
      adults was associated with lower ventral striatal activations to immediate
      reward. Furthermore, older adults showed an overall higher percentage of delayed
      choices and reduced activity in the dorsal striatum than younger adults. This
      points to a reduced reward sensitivity of the dorsal striatum in older adults.
      Taken together, our findings indicate that less impulsive decision-making in
      older adults is due to a reduced sensitivity of striatal areas to reward. These
      age-related changes in reward sensitivity may result from transformations in
      dopaminergic neuromodulation with age.

PMID- 22655033
TI  - Comparison of the virulence potential of Acinetobacter strains from clinical and
      environmental sources.
AB  - Several Acinetobacter strains have utility for biotechnology applications, yet
      some are opportunistic pathogens. We compared strains of seven Acinetobacter
      species (baumannii, Ab; calcoaceticus, Ac; guillouiae, Ag; haemolyticus, Ah;
      lwoffii, Al; junii, Aj; and venetianus, Av-RAG-1) for their potential virulence
      attributes, including proliferation in mammalian cell conditions,
      haemolytic/cytolytic activity, ability to elicit inflammatory signals, and
      antibiotic susceptibility. Only Ah grew at 10(2) and 10(4) bacteria/well in
      mammalian cell culture medium at 37 degrees C. However, co-culture with colonic
      epithelial cells (HT29) improved growth of all bacterial strains, except Av-RAG
      1. Cytotoxicity of Ab and Ah toward HT29 was at least double that of other test
      bacteria. These effects included bacterial adherence, loss of metabolism,
      substrate detachment, and cytolysis. Only Ab and Ah exhibited resistance to
      killing by macrophage-like J774A.1 cells. Haemolytic activity of Ah and Av-RAG-1
      was strong, but undetectable for other strains. When killed with an antibiotic,
      Ab, Ah, Aj and Av-RAG-1 induced 3 to 9-fold elevated HT29 interleukin (IL)-8
      levels. However, none of the strains altered levels of J774A.1 pro-inflammatory
      cytokines (IL-1beta, IL-6 and tumor necrosis factor-alpha). Antibiotic
      susceptibility profiling showed that Ab, Ag and Aj were viable at low
      concentrations of some antibiotics. All strains were positive for virulence
      factor genes ompA and epsA, and negative for mutations in gyrA and parC genes
      that convey fluoroquinolone resistance. The data demonstrate that Av-RAG-1, Ag
      and Al lack some potentially harmful characteristics compared to other
      Acinetobacter strains tested, but the biotechnology candidate Av-RAG-1 should be
      scrutinized further prior to widespread use.

PMID- 22655034
TI  - A complete sequence and transcriptomic analyses of date palm (Phoenix dactylifera
      L.) mitochondrial genome.
AB  - Based on next-generation sequencing data, we assembled the mitochondrial (mt)
      genome of date palm (Phoenix dactylifera L.) into a circular molecule of 715,001
      bp in length. The mt genome of P. dactylifera encodes 38 proteins, 30 tRNAs, and
      3 ribosomal RNAs, which constitute a gene content of 6.5% (46,770 bp) over the
      full length. The rest, 93.5% of the genome sequence, is comprised of cp
      (chloroplast)-derived (10.3% with respect to the whole genome length) and non
      coding sequences. In the non-coding regions, there are 0.33% tandem and 2.3% long
      repeats. Our transcriptomic data from eight tissues (root, seed, bud, fruit,
      green leaf, yellow leaf, female flower, and male flower) showed higher gene
      expression levels in male flower, root, bud, and female flower, as compared to
      four other tissues. We identified 120 potential SNPs among three date palm
      cultivars (Khalas, Fahal, and Sukry), and successfully found seven SNPs in the
      coding sequences. A phylogenetic analysis, based on 22 conserved genes of 15
      representative plant mitochondria, showed that P. dactylifera positions at the
      root of all sequenced monocot mt genomes. In addition, consistent with previous
      discoveries, there are three co-transcribed gene clusters-18S-5S rRNA, rps3-rpl16
      and nad3-rps12-in P. dactylifera, which are highly conserved among all known
      mitochondrial genomes of angiosperms.

PMID- 22655035
TI  - The alpine cushion plant Silene acaulis as foundation species: a bug's-eye view
      to facilitation and microclimate.
AB  - Alpine ecosystems are important globally with high levels of endemic and rare
      species. Given that they will be highly impacted by climate change, understanding
      biotic factors that maintain diversity is critical. Silene acaulis is a common
      alpine nurse plant shown to positively influence the diversity and abundance of
      organisms--predominantly other plant species. The hypothesis that cushion or
      nurse plants in general are important to multiple trophic levels has been
      proposed but rarely tested. Alpine arthropod diversity is also largely
      understudied worldwide, and the plant-arthropod interactions reported are mostly
      negative, that is,. herbivory. Plant and arthropod diversity and abundance were
      sampled on S. acaulis and at paired adjacent microsites with other non-cushion
      forming vegetation present on Whistler Mountain, B.C., Canada to examine the
      relative trophic effects of cushion plants. Plant species richness and abundance
      but not Simpson's diversity index was higher on cushion microsites relative to
      other vegetation. Arthropod richness, abundance, and diversity were all higher on
      cushion microsites relative to other vegetated sites. On a microclimatic scale,
      S. acaulis ameliorated stressful conditions for plants and invertebrates living
      inside it, but the highest levels of arthropod diversity were observed on
      cushions with tall plant growth. Hence, alpine cushion plants can be foundation
      species not only for other plant species but other trophic levels, and these
      impacts are expressed through both direct and indirect effects associated with
      altered environmental conditions and localized productivity. Whilst this case
      study tests a limited subset of the membership of alpine animal communities, it
      clearly demonstrates that cushion-forming plant species are an important
      consideration in understanding resilience to global changes for many organisms in
      addition to other plants.

PMID- 22655036
TI  - Cataract-causing defect of a mutant gamma-crystallin proceeds through an
      aggregation pathway which bypasses recognition by the alpha-crystallin chaperone.
AB  - BACKGROUND: The transparency of the eye lens depends upon maintenance of the
      native state of the gamma- and beta-crystallins, which is aided by the abundant
      chaperones alphaA- and alphaB-crystallin. Mature onset cataract, the leading
      cause of blindness worldwide, involves the polymerization of covalently damaged
      or partially unfolded crystallins into light-scattering aggregates. A number of
      single amino acid substitutions and truncations of gamma-crystallins result in
      congenital cataract in both humans and mice, though in many cases the coupling
      between the protein alterations and the accumulation of aggregates is poorly
      defined. METHODOLOGY/PRINCIPAL FINDINGS: We have studied the aggregation
      properties and chaperone interactions of human gammaD-crystallin carrying
      substitutions of two buried core mutants, I90F and V75D, which cause congenital
      cataract in mice. The in vitro aggregation pathway competing with productive
      refolding was not altered by either substitution. Furthermore, this aggregation
      pathway for both mutant proteins--originating from a partially folded
      intermediate--was efficiently suppressed by alphaB-crystallin. Thus the cataract
      pathology was unlikely to be associated with a direct folding defect. The native
      state of wild-type human gammaD-crystallin exhibited no tendency to aggregate
      under physiological conditions. However both I90F and V75D native-like proteins
      exhibited slow (days) aggregation to high molecular weight aggregates under
      physiological conditions. The perturbed conformation of I90F was recognized and
      bound by both alphaA and alphaB chaperones. In contrast, the aggregation derived
      from the perturbed state of V75D was not suppressed by either chaperone, and the
      aggregating species were not bound by the chaperone. CONCLUSIONS/SIGNIFICANCE:
      The cataract phenotype of I90F in mice may be due to premature saturation of the
      finite alpha- crystallin pool. The V75D aggregation pathway and its escape from
      chaperone surveillance and aggregation suppression can account for the congenital
      cataract pathology of this mutant. Failure of chaperone recognition may be an
      important source of pathology for many other protein folding defects.

PMID- 22655037
TI  - Seasonal movement and distribution of fluvial adult bull trout in selected
      watersheds in the mid-Columbia River and Snake River basins.
AB  - From 1997 to 2004, we used radio telemetry to investigate movement and
      distribution patterns of 206 adult fluvial bull trout (mean, 449 mm FL) from
      watersheds representing a wide range of habitat conditions in northeastern Oregon
      and southwestern Washington, a region for which there was little previous
      information about this species. Migrations between spawning and wintering
      locations were longest for fish from the Imnaha River (median, 89 km) and three
      Grande Ronde River tributaries, the Wenaha (56 km) and Lostine (41 km) rivers and
      Lookingglass Creek (47 km). Shorter migrations were observed in the John Day (8
      km), Walla Walla (20 km) and Umatilla river (22 km) systems, where relatively
      extensive human alterations of the riverscape have been reported. From November
      through May, fish displayed station-keeping behavior within a narrow range (basin
      medians, 0.5-6.2 km). Prespawning migrations began after snowmelt-driven peak
      discharge and coincided with declining flows. Most postspawning migrations began
      by late September. Migration rates of individuals ranged from 0.1 to 10.7 km/day.
      Adults migrated to spawning grounds in consecutive years and displayed strong
      fidelity to previous spawning areas and winter locations. In the Grande Ronde
      River basin, most fish displayed an unusual fluvial pattern: After exiting the
      spawning tributary and entering a main stem river, individuals moved upstream to
      wintering habitat, often a substantial distance (maximum, 49 km). Our work
      provides additional evidence of a strong migratory capacity in fluvial bull
      trout, but the short migrations we observed suggest adult fluvial migration may
      be restricted in basins with substantial anthropogenic habitat alteration. More
      research into bull trout ecology in large river habitats is needed to improve our
      understanding of how adults establish migration patterns, what factors influence
      adult spatial distribution in winter, and how managers can protect and enhance
      fluvial populations.

PMID- 22655038
TI  - Phylogeny of the Infraorder Pentatomomorpha based on fossil and extant
      morphology, with description of a new fossil family from China.
AB  - BACKGROUND: An extinct new family of Pentatomomorpha, Venicoridae Yao, Ren & Cai
      fam. nov., with 2 new genera and 2 new species (Venicoris solaris Yao, Ren &
      Rider gen. & sp. nov. and Clavaticoris zhengi Yao, Ren & Cai gen. & sp. nov.) are
      described from the Early Cretaceous Yixian Formation in Northeast China.
      METHODOLOGY/PRINCIPAL FINDINGS: A cladistic analysis based on a combination of
      fossil and extant morphological characters clarified the phylogenetic status of
      the new family and has allowed the reconstruction of intersuperfamily and
      interfamily relationships within the Infraorder Pentatomomorpha. The fossil
      record and diversity of Pentatomomorpha during the Mesozoic is discussed.
      CONCLUSIONS/SIGNIFICANCE: Pentatomomorpha is a monophyletic group; Aradoidea and
      the Trichophora are sister groups; these fossils belong to new family, treated as
      the sister group of remainder of Trichophora; Pentatomoidea is a monophyletic
      group; Piesmatidae should be separated as a superfamily, Piesmatoidea. Origin
      time of Pentatomomorpha should be tracked back to the Middle or Early Triassic.

PMID- 22655039
TI  - Two plant bacteria, S. meliloti and Ca. Liberibacter asiaticus, share functional
      znuABC homologues that encode for a high affinity zinc uptake system.
AB  - The Znu system, encoded for by znuABC, can be found in multiple genera of
      bacteria and has been shown to be responsible for the import of zinc under low
      zinc conditions. Although this high-affinity uptake system is known to be
      important for both growth and/or pathogenesis in bacteria, it has not been
      functionally characterized in a plant-associated bacterium. A single homologue of
      this system has been identified in the plant endosymbiont, Sinorhizobium
      meliloti, while two homologous systems were found in the destructive citrus
      pathogen, Candidatus Liberibacter asiaticus. To understand the role of these
      protein homologues, a complementation assay was devised allowing the individual
      genes that comprise the system to be assayed independently for their ability to
      reinstate a partially-inactivated Znu system. Results from the assays have
      demonstrated that although all of the genes from S. meliloti were able to restore
      activity, only one of the two Ca. Liberibacter asiaticus encoded gene clusters
      contained genes that were able to functionally complement the system. Additional
      analysis of the gene clusters reveals that distinct modes of regulation may also
      exist between the Ca. Liberibacter asiaticus and S. meliloti import systems
      despite the intracellular-plant niche common to both of these bacteria.

PMID- 22655041
TI  - Transferring learning from external to internal weights in echo-state networks
      with sparse connectivity.
AB  - Modifying weights within a recurrent network to improve performance on a task has
      proven to be difficult. Echo-state networks in which modification is restricted
      to the weights of connections onto network outputs provide an easier alternative,
      but at the expense of modifying the typically sparse architecture of the network
      by including feedback from the output back into the network. We derive methods
      for using the values of the output weights from a trained echo-state network to
      set recurrent weights within the network. The result of this "transfer of
      learning" is a recurrent network that performs the task without requiring the
      output feedback present in the original network. We also discuss a hybrid version
      in which online learning is applied to both output and recurrent weights. Both
      approaches provide efficient ways of training recurrent networks to perform
      complex tasks. Through an analysis of the conditions required to make transfer of
      learning work, we define the concept of a "self-sensing" network state, and we
      compare and contrast this with compressed sensing.

PMID- 22655040
TI  - Continuous regional arterial infusion with fluorouracil and octreotide attenuates
      severe acute pancreatitis in a canine model.
AB  - AIM: To investigate the therapeutic effects of fluorouracil (5-Fu) and octreotide
      (Oct) continuous regional arterial infusion (CRAI,) alone or in combination, was
      administered in a canine model of severe acute pancreatitis (SAP). MATERIALS AND
      METHODS: The animals were divided into five groups; group A (Sham), group B
      (SAP), group C (SAP and 5-Fu), group D (SAP and Oct), and group E (SAP and 5-Fu +
      Oct). Levels of amylase, alpha-tumor necrosis factor (TNF-alpha), blood urea
      nitrogen (BUN), creatinine, thromboxane B2 and 6-keto- prostaglandin F1alpha were
      measured both before and after the induction of SAP. Pathologic examination of
      the pancreas and kidneys was performed after termination of the study. RESULTS:
      Pathologic changes noted in the pancreas in SAP significantly improved following
      CRAI with either single or combined administration of 5-Fu and Oct, where
      combination therapy demonstrated the lowest injury score. All treatment groups
      had significantly lower levels of serum TNF-alpha and amylase activity (P<0.05),
      though only groups D and E had a lower BUN level as compared to group B. The
      plasma thromboxane B(2) level increased in SAP, but the ratio of thromboxane
      B(2)/6-keto- prostaglandin F(1alpha) decreased in the treatment groups, with the
      combination therapy (group E) demonstrating the lowest ratio as compared to the
      other 3 experimental groups (P<0.05). CONCLUSIONS: The findings in the present
      study demonstrate an attenuation of SAP in a canine model following CRAI
      administration with 5-Fu or Oct, alone or in combination.

PMID- 22655042
TI  - Long-term effects of autologous bone marrow stem cell treatment in acute
      myocardial infarction: factors that may influence outcomes.
AB  - AIMS: To investigate whether there are important sources of heterogeneity between
      the findings of different clinical trials which administer autologous stem cell
      treatment for acute myocardial infarction (AMI) and to evaluate what factors may
      influence the long-term effects of this treatment. METHODS AND RESULTS: MEDLINE
      (1950-January 2011), EMBASE (1974-January 2011), CENTRAL (The Cochrane Library
      2011, Issue 1), CINAHL (1982-January 2011), and ongoing trials registers were
      searched for randomised trials of bone marrow stem cells as treatment for AMI.
      Hand-searching was used to screen recent, relevant conference proceedings (2005
      2010/11). Meta-analyses were conducted using random-effects models and
      heterogeneity between subgroups was assessed using chi-squared tests. Planned
      analyses included length of follow-up, timing of cell infusion and dose, patient
      selection, small trial size effect, methodological quality, loss of follow-up and
      date of publication. Thirty-three trials with a total of 1,765 participants were
      included. There was no evidence of bias due to publication or time-lag,
      methodological quality of included studies, participant drop-out, duration of
      follow-up or date of the first disclosure of results. However, in long-term
      follow-ups the treatment seemed more effective when administered at doses greater
      than 10(8) cells and to patients with more severe heart dysfunction. CONCLUSIONS:
      Evaluation of heterogeneity between trials has not identified significant sources
      of bias in this study. However, clinical differences between trials are likely to
      exist which should be considered when undertaking future trials.

PMID- 22655044
TI  - Changes in inflammatory response after endovascular treatment for type B aortic
      dissection.
AB  - This present study aims to investigate the changes in the inflammatory markers
      after elective endovascular treatment of Type B aortic dissection with aneurysm,
      as related to different anatomical features of the dissection flap in the
      paravisceral perfusion. Consecutive patients with type B aortic dissections with
      elective endovascular stent graft repair were recruited and categorized into
      different groups. Serial plasma levels of cytokines (Interleukin-1beta, -6, -8, 
      10, TNF-alpha), chemokines (MCP-1), and serum creatinine were monitored at pre-,
      peri- and post-operative stages. The length of stent graft employed in each
      surgery was retrieved and correlated with the change of all studied biochemical
      parameters. A control group of aortic dissected patients with conventional
      medication management was recruited for comparing the baseline biochemical
      parameters. In total, 22 endovascular treated and 16 aortic dissected patients
      with surveillance were recruited. The endovascular treated patients had
      comparable baseline levels as the non-surgical patients. There was no immediate
      or thirty day-mortality, and none of the surgical patients developed post
      operative mesenteric ischaemia or clinically significant renal impairment. All
      surgical patients had detectable pro-inflammatory mediators, but none of the them
      showed any statistical significant surge in the peri-operative period except IL
      1beta and IL-6. Similar results were obtained when categorized into different
      groups. IL-1beta and IL-6 showed maximal levels within hours of the endovascular
      procedure (range, 3.93 to 27.3 higher than baseline; p = 0.001), but returned to
      baseline 1 day post-operatively. The change of IL-1beta and IL-6 at the stent
      graft deployment was statistically greater in longer stent graft (p>0.05). No
      significant changes were observed in the serum creatinine levels. In conclusion,
      elective endovascular repair of type B aortic dissection associated with
      insignificant changes in inflammatory mediators and creatinine. All levels fell
      toward basal levels post-operatively suggesting that thoracic endovascular aortic
      repair is rather less aggressive with insignificant inflammatory modulation.

PMID- 22655043
TI  - Shifting the paradigm: the putative mitochondrial protein ABCB6 resides in the
      lysosomes of cells and in the plasma membrane of erythrocytes.
AB  - ABCB6, a member of the adenosine triphosphate-binding cassette (ABC) transporter
      family, has been proposed to be responsible for the mitochondrial uptake of
      porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of
      mature erythrocytes and in exosomes released from reticulocytes during the final
      steps of erythroid maturation. Consistent with its presence in exosomes,
      endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent
      from the mitochondria of cells. Knock-down studies demonstrate that ABCB6
      function is not required for de novo heme biosynthesis in differentiating K562
      cells, excluding this ABC transporter as a key regulator of porphyrin synthesis.
      We confirm the mitochondrial localization of ABCB7, ABCB8 and ABCB10, suggesting
      that only three ABC transporters should be classified as mitochondrial proteins.
      Taken together, our results challenge the current paradigm linking the expression
      and function of ABCB6 to mitochondria.

PMID- 22655045
TI  - Secretogranin II; a protein increased in the myocardium and circulation in heart
      failure with cardioprotective properties.
AB  - BACKGROUND: Several beneficial effects have been demonstrated for secretogranin
      II (SgII) in non-cardiac tissue. As cardiac production of chromogranin A and B,
      two related proteins, is increased in heart failure (HF), we hypothesized that
      SgII could play a role in cardiovascular pathophysiology. METHODOLOGY/PRINCIPAL
      FINDINGS: SgII production was characterized in a post-myocardial infarction heart
      failure (HF) mouse model, functional properties explored in experimental models,
      and circulating levels measured in mice and patients with stable HF of moderate
      severity. SgII mRNA levels were 10.5 fold upregulated in the left ventricle (LV)
      of animals with myocardial infarction and HF (p<0.001 vs. sham-operated animals).
      SgII protein levels were also increased in the LV, but not in other organs
      investigated. SgII was produced in several cell types in the myocardium and
      cardiomyocyte synthesis of SgII was potently induced by transforming growth
      factor-beta and norepinephrine stimulation in vitro. Processing of SgII to
      shorter peptides was enhanced in the failing myocardium due to increased levels
      of the proteases PC1/3 and PC2 and circulating SgII levels were increased in mice
      with HF. Examining a pathophysiological role of SgII in the initial phase of post
      infarction HF, the SgII fragment secretoneurin reduced myocardial ischemia
      reperfusion injury and cardiomyocyte apoptosis by 30% and rapidly increased
      cardiomyocyte Erk1/2 and Stat3 phosphorylation. SgII levels were also higher in
      patients with stable, chronic HF compared to age- and gender-matched control
      subjects: median 0.16 (Q1-3 0.14-0.18) vs. 0.12 (0.10-0.14) nmol/L, p<0.001.
      CONCLUSIONS: We demonstrate increased myocardial SgII production and processing
      in the LV in animals with myocardial infarction and HF, which could be beneficial
      as the SgII fragment secretoneurin protects from ischemia-reperfusion injury and
      cardiomyocyte apoptosis. Circulating SgII levels are also increased in patients
      with chronic, stable HF and may represent a new cardiac biomarker.

PMID- 22655046
TI  - Full-exon pyrosequencing screening of BRCA germline mutations in Mexican women
      with inherited breast and ovarian cancer.
AB  - Hereditary breast cancer comprises 10% of all breast cancers. The most prevalent
      genes causing this pathology are BRCA1 and BRCA2 (breast cancer early onset 1 and
      2), which also predispose to other cancers. Despite the outstanding relevance of
      genetic screening of BRCA deleterious variants in patients with a history of
      familial cancer, this practice is not common in Latin American public
      institutions. In this work we assessed mutations in the entire exonic and splice
      site regions of BRCA in 39 patients with breast and ovarian cancer and with
      familial history of breast cancer or with clinical features suggestive for BRCA
      mutations by massive parallel pyrosequencing. First we evaluated the method with
      controls and found 41-485 reads per sequence in BRCA pathogenic mutations.
      Negative controls did not show deleterious variants, confirming the suitability
      of the approach. In patients diagnosed with cancer we found 4 novel deleterious
      mutations (c.2805_2808delAGAT and c.3124_3133delAGCAATATTA in BRCA1;
      c.2639_2640delTG and c.5114_5117delTAAA in BRCA2). The prevalence of BRCA
      mutations in these patients was 10.2%. Moreover, we discovered 16 variants with
      unknown clinical significance (11 in exons and 5 in introns); 4 were predicted as
      possibly pathogenic by in silico analyses, and 3 have not been described
      previously. This study illustrates how massive pyrosequencing technology can be
      applied to screen for BRCA mutations in the whole exonic and splice regions in
      patients with suspected BRCA-related cancers. This is the first effort to analyse
      the mutational status of BRCA genes on a Mexican-mestizo population by means of
      pyrosequencing.

PMID- 22655047
TI  - Is it time for a change? A cost-effectiveness analysis comparing a
      multidisciplinary integrated care model for residential homes to usual care.
AB  - OBJECTIVE: The objective of this study was to evaluate the cost-effectiveness of
      a Multidisciplinary Integrated Care (MIC) model compared to Usual Care (UC) in
      Dutch residential homes. METHODS: The economic evaluation was conducted from a
      societal perspective alongside a 6 month, clustered, randomized controlled trial
      involving 10 Dutch residential homes. Outcome measures included a quality of care
      weighted sum score, functional health (COOP WONCA) and Quality Adjusted Life
      Years (QALY). Missing cost and effect data were imputed using multiple
      imputation. Bootstrapping was used to analyze differences in costs and cost
      effectiveness. RESULTS: The quality of care sum score in MIC was significantly
      higher than in UC. The other primary outcomes showed no significant differences
      between the MIC and UC. The costs of providing MIC were approximately ?225 per
      patient. Total costs were ?2,061 in the MIC group and ?1,656 for the UC group
      (mean difference ?405, 95% -13; 826). The probability that the MIC was cost
      effective in comparison with UC was 0.95 or more for ceiling ratios larger than
      ?129 regarding patient related quality of care. Cost-effectiveness planes showed
      that the MIC model was not cost-effective compared to UC for the other outcomes.
      INTERPRETATION: Clinical effect differences between the groups were small but
      quality of care was significantly improved in the MIC group. Short term costs for
      MIC were higher. Future studies should focus on longer term economic and clinical
      effects. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN11076857.

PMID- 22655048
TI  - Activation of BK(Ca) channels in zoledronic acid-induced apoptosis of MDA-MB-231
      breast cancer cells.
AB  - BACKGROUND: Zoledronic acid, one of the most potent nitrogen-containing
      biphosphonates, has been demonstrated to have direct anti-tumor and anti
      metastatic properties in breast cancer in vitro and in vivo. In particular, tumor
      cell apoptosis has been recognized to play an important role in the treatment of
      metastatic breast cancer with zoledronic acid. However, the precise mechanisms
      remain less clear. In the present study, we investigated the specific role of
      large conductance Ca(2+)-activated potassium (BK(Ca)) channel in zoledronic acid
      induced apoptosis of estrogen receptor (ER)-negative MDA-MB-231 breast cancer
      cells. METHODOLOGY/PRINCIPAL FINDINGS: The action of zoledronic acid on BK(Ca)
      channel was investigated by whole-cell and cell-attached patch clamp techniques.
      Cell apoptosis was assessed with immunocytochemistry, analysis of fragmented DNA
      by agarose gel electrophoresis, and flow cytometry assays. Cell proliferation was
      investigated by MTT test and immunocytochemistry. In addition, such findings were
      further confirmed with human embryonic kidney 293 (HEK293) cells which were
      transfected with functional BK(Ca) alpha-subunit (hSloalpha). Our results clearly
      indicated that zoledronic acid directly increased the activities of BK(Ca)
      channels, and then activation of BK(Ca) channel by zoledronic acid contributed to
      induce apoptosis in MDA-MB-231 cells. The possible mechanisms were associated
      with the elevated level of intracellular Ca(2+) and a concomitant depolarization
      of mitochondrial membrane potential (Deltapsim) in MDA-MB-231 cells. CONCLUSIONS:
      Activation of BK(Ca) channel was here shown to be a novel molecular pathway
      involved in zoledronic acid-induced apoptosis of MDA-MB-231 cells in vitro.

PMID- 22655050
TI  - Multiple mating and family structure of the western tent caterpillar, Malacosoma
      californicum pluviale: impact on disease resistance.
AB  - BACKGROUND: Levels of genetic diversity can strongly influence the dynamics and
      evolutionary changes of natural populations. Survival and disease resistance have
      been linked to levels of genetic diversity in eusocial insects, yet these
      relationships remain untested in gregarious insects where disease transmission
      can be high and selection for resistance is likely to be strong.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we use 8 microsatellite loci to examine
      genetic variation in 12 families of western tent caterpillars, Malacosoma
      californicum pluviale from four different island populations to determine the
      relationship of genetic variability to survival and disease resistance. In
      addition these genetic markers were used to elucidate the population structure of
      western tent caterpillars. Multiple paternity was revealed by microsatellite
      markers, with the number of sires estimated to range from one to three per family
      (mean +/- SE  = 1.92+/-0.23). Observed heterozygosity (H(O)) of families was not
      associated to the resistance of families to a nucleopolyhedrovirus (NPV) (r =
      0.161, F(1,12)  = 0.271, P = 0.614), a major cause of mortality in high-density
      populations, but was positively associated with larval survival (r = 0.635,
      F(1,10)  = 5.412, P = 0.048). Genetic differentiation among the families was high
      (F(ST) = 0.269, P<0.0001), and families from the same island were as
      differentiated as were families from other islands. CONCLUSION/SIGNIFICANCE: We
      have been able to describe and characterize 8 microsatellite loci, which
      demonstrate patterns of variation within and between families of western tent
      caterpillars. We have discovered an association between larval survival and
      family-level heterozygosity that may be relevant to the population dynamics of
      this cyclic forest lepidopteran, and this will be the topic of future work.

PMID- 22655049
TI  - The dUTPase enzyme is essential in Mycobacterium smegmatis.
AB  - Thymidine biosynthesis is essential in all cells. Inhibitors of the enzymes
      involved in this pathway (e.g. methotrexate) are thus frequently used as
      cytostatics. Due to its pivotal role in mycobacterial thymidylate synthesis
      dUTPase, which hydrolyzes dUTP into the dTTP precursor dUMP, has been suggested
      as a target for new antitubercular agents. All mycobacterial genomes encode
      dUTPase with a mycobacteria-specific surface loop absent in the human dUTPase.
      Using Mycobacterium smegmatis as a fast growing model for Mycobacterium
      tuberculosis, we demonstrate that dUTPase knock-out results in lethality that can
      be reverted by complementation with wild-type dUTPase. Interestingly, a mutant
      dUTPase gene lacking the genus-specific loop was unable to complement the knock
      out phenotype. We also show that deletion of the mycobacteria-specific loop has
      no major effect on dUTPase enzymatic properties in vitro and thus a yet to be
      identified loop-specific function seems to be essential within the bacterial cell
      context. In addition, here we demonstrated that Mycobacterium tuberculosis
      dUTPase is fully functional in Mycobacterium smegmatis as it rescues the lethal
      knock-out phenotype. Our results indicate the potential of dUTPase as a target
      for antitubercular drugs and identify a genus-specific surface loop on the enzyme
      as a selective target.

PMID- 22655051
TI  - Identification of Sare0718 as an alanine-activating adenylation domain in marine
      actinomycete Salinispora arenicola CNS-205.
AB  - BACKGROUND: Amino acid adenylation domains (A domains) are critical enzymes that
      dictate the identity of the amino acid building blocks to be incorporated during
      nonribosomal peptide (NRP) biosynthesis. NRPs represent a large group of valuable
      natural products that are widely applied in medicine, agriculture, and
      biochemical research. Salinispora arenicola CNS-205 is a representative strain of
      the first discovered obligate marine actinomycete genus, whose genome harbors a
      large number of cryptic secondary metabolite gene clusters. METHODOLOGY/PRINCIPAL
      FINDINGS: In order to investigate cryptic NRP-related metabolites in S. arenicola
      CNS-205, we cloned and identified the putative gene sare0718 annotated "amino
      acid adenylation domain". Firstly, the general features and possible functions of
      sare0718 were predicted by bioinformatics analysis, which suggested that Sare0718
      is a soluble protein with an AMP-binding domain contained in the sequence and its
      cognate substrate is L-Val. Then, a GST-tagged fusion protein was expressed and
      purified to further explore the exact adenylation activity of Sare0718 in vitro.
      By a newly mentioned nonradioactive malachite green colorimetric assay, we found
      that L-Ala but not L-Val is the actual activated amino acid substrate and the
      basic kinetic parameters of Sare0718 for it are K(m) = 0.1164+/-0.0159 (mM),
      V(max) = 3.1484+/-0.1278 (uM/min), k(cat) = 12.5936+/-0.5112 (min(-1)).
      CONCLUSIONS/SIGNIFICANCE: By revealing the biochemical role of sare0718 gene, we
      identified an alanine-activating adenylation domain in marine actinomycete
      Salinispora arenicola CNS-205, which would provide useful information for next
      isolation and function elucidation of the whole cryptic nonribosomal peptide
      synthetase (NRPS)-related gene cluster covering Sare0718. And meanwhile, this
      work also enriched the biochemical data of A domain substrate specificity in
      newly discovered marine actinomycete NRPS system, which bioinformatics prediction
      will largely depend on.

PMID- 22655052
TI  - Assessing the short-term effects of heatwaves on mortality and morbidity in
      Brisbane, Australia: comparison of case-crossover and time series analyses.
AB  - BACKGROUND: Heat-related impacts may have greater public health implications as
      climate change continues. It is important to appropriately characterize the
      relationship between heatwave and health outcomes. However, it is unclear whether
      a case-crossover design can be effectively used to assess the event- or episode
      related health effects. This study examined the association between exposure to
      heatwaves and mortality and emergency hospital admissions (EHAs) from non
      external causes in Brisbane, Australia, using both case-crossover and time series
      analyses approaches. METHODS: Poisson generalised additive model (GAM) and time
      stratified case-crossover analyses were used to assess the short-term impact of
      heatwaves on mortality and EHAs. Heatwaves exhibited a significant impact on
      mortality and EHAs after adjusting for air pollution, day of the week, and
      season. RESULTS: For time-stratified case-crossover analysis, odds ratios of
      mortality and EHAs during heatwaves were 1.62 (95% confidence interval (CI): 1.36
      1.94) and 1.22 (95% CI: 1.14-1.30) at lag 1, respectively. Time series GAM models
      gave similar results. Relative risks of mortality and EHAs ranged from 1.72 (95%
      CI: 1.40-2.11) to 1.81 (95% CI: 1.56-2.10) and from 1.14 (95% CI: 1.06-1.23) to
      1.28 (95% CI: 1.21-1.36) at lag 1, respectively. The risk estimates gradually
      attenuated after the lag of one day for both case-crossover and time series
      analyses. CONCLUSIONS: The risk estimates from both case-crossover and time
      series models were consistent and comparable. This finding may have implications
      for future research on the assessment of event- or episode-related (e.g.,
      heatwave) health effects.

PMID- 22655053
TI  - Impact of obesity on the bioavailability of peginterferon-alpha2a and ribavirin
      and treatment outcome for chronic hepatitis C genotype 2 or 3.
AB  - BACKGROUND AND AIMS: Having a body mass index above or equal to 30 kg/m(2) in
      conjunction with chronic hepatitis C virus infection is associated with non
      responsiveness to treatment with interferon and ribavirin, but details regarding
      the mechanisms whereby obesity reduces the efficacy of therapy remain unclear.
      METHODS: This study evaluated impact of obesity on outcome as well as interferon
      and ribavirin concentrations following standard-of-care fixed dosing with
      peginterferon-alpha2a 180 ug once weekly and ribavirin 800 mg daily among 303 HCV
      genotype 2/3-infected patients enrolled in the per-protocol analysis of a
      recently completed phase III trial (NORDynamIC). RESULTS: Patients with BMI >=30
      kg/m(2) showed poorer outcome following 24 weeks of therapy (SVR 62% vs. 89% for
      BMI >=30 vs. <30; P = 0.006) along with significantly higher steatosis grade (P =
      0.002), HOMA-IR (P<0.0001), triglyceride levels (P = 0.0002), and baseline viral
      load (P = 0.028). Obesity was also significantly associated with lower plasma
      interferon concentrations on days 3, 7, and 29 (P = 0.02, P = 0.0017, and
      P<0.0001, respectively) and lower plasma ribavirin concentrations day 29 (P =
      0.025), and lower concentration of interferon in turn was associated with a
      poorer first phase reduction in HCV RNA (P<0.0001). In multivariate analysis,
      ribavirin concentrations week 12, interferon concentrations day 29, and baseline
      HCV RNA levels were independent predictors of achieving SVR among patients
      treated for 24 weeks (n = 140). CONCLUSIONS: Reduced bioavailability of
      interferon and ribavirin along with higher baseline viral load are dominant risk
      factors for treatment failure in obese patients with chronic hepatitis C.

PMID- 22655054
TI  - Comparison of two high-throughput assays for quantification of adenovirus type 5
      neutralizing antibodies in a population of donors in China.
AB  - BACKGROUND: The presence of various levels of Adenovirus serotype 5 neutralizing
      antibodies (Ad5NAb) is thought to contribute to the inconsistent clinical results
      obtained from vaccination and gene therapy studies. Currently, two platforms
      based on high-throughput technology are available for Ad5NAb quantification,
      chemiluminescence- and fluorescence-based assays. The aim of this study was to
      compare the results of two assays in the seroepidemiology of Ad5NAb in a local
      population of donors. METHODOLOGY/PRINCIPAL FINDINGS: The fluorescence-based
      neutralizing antibody detection test (FRNT) using recombinant Ad5-EGFP virus and
      the chemiluminescence-based neutralizing antibody test (CLNT) using Ad5-Fluc were
      developed and standardized for detecting the presence of Ad5NAb in serum samples
      from the population of donors in Beijing and Anhui provinces, China. First, the
      overall percentage of people positive for Ad5NAb performed by CLNT was higher
      than that obtained by FRNT (85.4 vs 69.9%, p<0.001). There was an 84.5%
      concordance between the two assays for the 206 samples tested (144 positive in
      both assays and 30 negative in both assays). All 32 discordant sera were CLNT
      positive/FRNT-negative and were confirmed positive by western blot. Secondly, for
      all 144 sera positive by both assays, the two assays showed high correlation (r =
      0.94, p<0.001) and close agreement (mean difference: 0.395 log(10), 95% CI: 
      0.054 log(10) to 0.845 log(10)). Finally, it was found by both assays that there
      was no significant difference observed for titer or prevalence by gender (p =
      0.503 vs 0.818, for two assays); however, age range (p = 0.049 vs 0.010) and
      geographic origin (p = 0.007 vs 0.011) were correlated with Ad5NAb prevalence in
      northern regions of China. CONCLUSION: The CLNT assay was relatively more simple
      and had higher sensitivity than the FRNT assay for determining Ad5NAb titers. It
      is strongly suggested that the CLNT assay be used for future epidemiological
      studies of Ad5NAb in other localities.

PMID- 22655055
TI  - Testing for differentially-expressed microRNAs with errors-in-variables
      nonparametric regression.
AB  - MicroRNA is a set of small RNA molecules mediating gene expression at post
      transcriptional/translational levels. Most of well-established high throughput
      discovery platforms, such as microarray, real time quantitative PCR, and
      sequencing, have been adapted to study microRNA in various human diseases. The
      total number of microRNAs in humans is approximately 1,800, which challenges some
      analytical methodologies requiring a large number of entries. Unlike messenger
      RNA, the majority of microRNA (>60%) maintains relatively low abundance in the
      cells. When analyzed using microarray, the signals of these low-expressed
      microRNAs are influenced by other non-specific signals including the background
      noise. It is crucial to distinguish the true microRNA signals from measurement
      errors in microRNA array data analysis. In this study, we propose a novel
      measurement error model-based normalization method and differentially-expressed
      microRNA detection method for microRNA profiling data acquired from locked
      nucleic acids (LNA) microRNA array. Compared with some existing methods, the
      proposed method significantly improves the detection among low-expressed
      microRNAs when assessed by quantitative real-time PCR assay.

PMID- 22655056
TI  - Density-dependent processes in the life history of fishes: evidence from
      laboratory populations of zebrafish Danio rerio.
AB  - Population regulation is fundamental to the long-term persistence of populations
      and their responses to harvesting, habitat modification, and exposure to toxic
      chemicals. In fish and other organisms with complex life histories, regulation
      may involve density dependence in different life-stages and vital rates. We
      studied density dependence in body growth and mortality through the life-cycle of
      laboratory populations of zebrafish Danio rerio. When feed input was held
      constant at population-level (leading to resource limitation), body growth was
      strongly density-dependent in the late juvenile and adult phases of the life
      cycle. Density dependence in mortality was strong during the early juvenile phase
      but declined thereafter and virtually ceased prior to maturation. Provision of
      feed in proportion to individual requirements (easing resource limitation)
      removed density dependence in growth and substantially reduced density dependence
      in mortality, thus indicating that 'bottom-up' effects act on growth as well as
      mortality, but most strongly on growth. Both growth and mortality played an
      important role in population regulation, with density-dependent growth having the
      greater impact on population biomass while mortality had the greatest impact on
      numbers. We demonstrate a clear ontogenic pattern of change in density-dependent
      processes within populations of a very small (maximum length 5 mm) fish,
      maintained in constant homogeneous laboratory conditions. The patterns are
      consistent with those distilled from studies on wild fish populations, indicating
      the presence of broad ontogenic patterns in density-dependent processes that are
      invariant to maximum body size and hold in homogeneous laboratory, as well as
      complex natural environments.

PMID- 22655057
TI  - Co-localized or randomly distributed? Pair cross correlation of in vivo grown
      subgingival biofilm bacteria quantified by digital image analysis.
AB  - The polymicrobial nature of periodontal diseases is reflected by the diversity of
      phylotypes detected in subgingival plaque and the finding that consortia of
      suspected pathogens rather than single species are associated with disease
      development. A number of these microorganisms have been demonstrated in vitro to
      interact and enhance biofilm integration, survival or even pathogenic features.
      To examine the in vivo relevance of these proposed interactions, we extended the
      spatial arrangement analysis tool of the software daime (digital image analysis
      in microbial ecology). This modification enabled the quantitative analysis of
      microbial co-localization in images of subgingival biofilm species, where the
      biomass was confined to fractions of the whole-image area, a situation common for
      medical samples. Selected representatives of the disease-associated red and
      orange complexes that were previously suggested to interact with each other in
      vitro (Tannerella forsythia with Fusobacterium nucleatum and Porphyromonas
      gingivalis with Prevotella intermedia) were chosen for analysis and labeled with
      specific fluorescent probes via fluorescence in situ hybridization. Pair cross
      correlation analysis of in vivo grown biofilms revealed tight clustering of F.
      nucleatum/periodonticum and T. forsythia at short distances (up to 6 um) with a
      pronounced peak at 1.5 um. While these results confirmed previous in vitro
      observations for F. nucleatum and T. forsythia, random spatial distribution was
      detected between P. gingivalis and P. intermedia in the in vivo samples. In
      conclusion, we successfully employed spatial arrangement analysis on the single
      cell level in clinically relevant medical samples and demonstrated the utility of
      this approach for the in vivo validation of in vitro observations by analyzing
      statistically relevant numbers of different patients. More importantly, the
      culture-independent nature of this approach enables similar quantitative analyses
      for "as-yet-uncultured" phylotypes which cannot be characterized in vitro.

PMID- 22655058
TI  - TLR2, TLR4 and the MYD88 signaling pathway are crucial for neutrophil migration
      in acute kidney injury induced by sepsis.
AB  - The aim of this study was to investigate the role of TLR2, TLR4 and MyD88 in
      sepsis-induced AKI. C57BL/6 TLR2(-/-), TLR4(-/-) and MyD88(-/-) male mice were
      subjected to sepsis by cecal ligation and puncture (CLP). Twenty four hours
      later, kidney tissue and blood samples were collected for analysis. The TLR2(-/
      ), TLR4(-/-) and MyD88(-/-) mice that were subjected to CLP had preserved renal
      morphology, and fewer areas of hypoxia and apoptosis compared with the wild-type
      C57BL/6 mice (WT). MyD88(-/-) mice were completely protected compared with the WT
      mice. We also observed reduced expression of proinflammatory cytokines in the
      kidneys of the knockout mice compared with those of the WT mice and subsequent
      inhibition of increased vascular permeability in the kidneys of the knockout
      mice. The WT mice had increased GR1(+low) cells migration compared with the
      knockout mice and decreased in GR1(+high) cells migration into the peritoneal
      cavity. The TLR2(-/-), TLR4(-/-), and MyD88(-/-) mice had lower neutrophil
      infiltration in the kidneys. Depletion of neutrophils in the WT mice led to
      protection of renal function and less inflammation in the kidneys of these mice.
      Innate immunity participates in polymicrobial sepsis-induced AKI, mainly through
      the MyD88 pathway, by leading to an increased migration of neutrophils to the
      kidney, increased production of proinflammatory cytokines, vascular permeability,
      hypoxia and apoptosis of tubular cells.

PMID- 22655059
TI  - Microarray analysis of gene regulations and potential association with acephate
      resistance and fitness cost in Lygus lineolaris.
AB  - The tarnished plant bug has become increasingly resistant to organophosphates in
      recent years. To better understand acephate resistance mechanisms, biological,
      biochemical, and molecular experiments were systematically conducted with
      susceptible (LLS) and acephate-selected (LLR) strains. Selection of a field
      population with acephate significantly increased resistance ratio to 5.9-fold,
      coupled with a significant increase of esterase activities by 2-fold. Microarray
      analysis of 6,688 genes revealed 329 up- and 333 down-regulated (>=2-fold) genes
      in LLR. Six esterase, three P450, and one glutathione S-transferase genes were
      significantly up-regulated, and no such genes were down-regulated in LLR. All
      vitellogenin and eggshell protein genes were significantly down-regulated in LLR.
      Thirteen protease genes were significantly down-regulated and only 3 were up
      regulated in LLR. More than twice the number of catalysis genes and more than 3.6
      fold of metabolic genes were up-regulated, respectively, as compared to those
      down-regulated with the same molecular and biological functions. The large
      portion of metabolic or catalysis genes with significant up-regulations indicated
      a substantial increase of metabolic detoxification in LLR. Significant increase
      of acephate resistance, increases of esterase activities and gene expressions,
      and variable esterase sequences between LLS and LLR consistently demonstrated a
      major esterase-mediated resistance in LLR, which was functionally provable by
      abolishing the resistance with esterase inhibitors. In addition, significant
      elevation of P450 gene expression and reduced susceptibility to imidacloprid in
      LLR indicated a concurrent resistance risk that may impact other classes of
      insecticides. This study demonstrated the first association of down-regulation of
      reproductive- and digestive-related genes with resistance to conventional
      insecticides, suggesting potential fitness costs associated with resistance
      development. This study shed new light on the understanding of the molecular
      basis of insecticide resistance, and the information is highly valuable for
      development of chemical control guidelines and tactics to minimize resistance and
      cross-resistance risks.

PMID- 22655060
TI  - Recovery in stroke rehabilitation through the rotation of preferred directions
      induced by bimanual movements: a computational study.
AB  - Stroke patients recover more effectively when they are rehabilitated with
      bimanual movement rather than with unimanual movement; however, it remains
      unclear why bimanual movement is more effective for stroke recovery. Using a
      computational model of stroke recovery, this study suggests that bimanual
      movement facilitates the reorganization of a damaged motor cortex because this
      movement induces rotations in the preferred directions (PDs) of motor cortex
      neurons. Although the tuning curves of these neurons differ during unimanual and
      bimanual movement, changes in PD, but not changes in modulation depth, facilitate
      such reorganization. In addition, this reorganization was facilitated only when
      encoding PDs are rotated, but decoding PDs are not rotated. Bimanual movement
      facilitates reorganization because this movement changes neural activities
      through inter-hemispheric inhibition without changing cortical-spinal-muscle
      connections. Furthermore, stronger inter-hemispheric inhibition between motor
      cortices results in more effective reorganization. Thus, this study suggests that
      bimanual movement is effective for stroke rehabilitation because this movement
      rotates the encoding PDs of motor cortex neurons.

PMID- 22655061
TI  - Meandering main pancreatic duct as a relevant factor to the onset of idiopathic
      recurrent acute pancreatitis.
AB  - BACKGROUND: Meandering main pancreatic duct (MMPD), which comprises loop type and
      reverse-Z type main pancreatic duct (MPD), has long been discussed its relation
      to pancreatitis. However, no previous study has investigated its clinical
      significance. We aimed to determine the non-biased prevalence and the effect of
      MMPD on idiopathic pancreatitis using non-invasive magnetic resonance (MR)
      technique. METHODS AND FINDINGS: A cross-sectional study performed in a tertiary
      referral center. The study enrolled 504 subjects from the community and 30
      patients with idiopathic pancreatitis (7 acute, 13 chronic, and 10 recurrent
      acute). All subjects underwent MR scanning and medical examination. MMPD was
      diagnosed when the MPD in the head of pancreas formed two or more extrema in the
      horizontal direction on coronal images of MR cholangiopancreatography, making a
      loop or a reverse-Z shaped hairpin curves and not accompanied by other pancreatic
      ductal anomaly. Statistical comparison was made among groups on the rate of MMPD
      including loop and reverse-Z subtypes, MR findings, and clinical features. The
      rate of MMPD was significantly higher for all idiopathic pancreatitis/idiopathic
      recurrent acute pancreatitis (RAP) (20%/40%; P<0.001/0.0001; odds ratio (OR),
      11.1/29.0) than in the community (2.2%) but was not higher for acute/chronic
      pancreatitis (14%/8%; P = 0.154/0.266). Multiple logistic regression analysis
      revealed MMPD to be a significant factor that induces pancreatitis/RAP
      (P<0.0001/0.0001; OR, 4.01/26.2). Loop/reverse-Z subtypes were found more
      frequently in idiopathic RAP subgroup (20%/20%; P = 0.009/0.007; OR, 20.2/24.2)
      than in the community (1.2%/1.0%). The other clinical and radiographic features
      were shown not associated with the onset of pancreatitis. CONCLUSIONS: MMPD is a
      common anatomical variant and might be a relevant factor to the onset of
      idiopathic RAP.

PMID- 22655062
TI  - Prenatal hyperandrogenization induces metabolic and endocrine alterations which
      depend on the levels of testosterone exposure.
AB  - Prenatal hyperandrogenism is able to induce polycystic ovary syndrome (PCOS) in
      rats. The aim of the present study was to establish if the levels of prenatal
      testosterone may determine the extent of metabolic and endocrine alterations
      during the adult life. Pregnant Sprague Dawley rats were prenatally injected with
      either 2 or 5 mg free testosterone (groups T2 and T5 respectively) from day 16 to
      day 19 day of gestation. Female offspring from T2 and T5 displayed different
      phenotype of PCOS during adult life. Offspring from T2 showed hyperandrogenism,
      ovarian cysts and ovulatory cycles whereas those from T5 displayed
      hyperandrogenism, ovarian cysts and anovulatory cycles. Both group showed
      increased circulating glucose levels after the intraperitoneal glucose tolerance
      test (IPGTT; an evaluation of insulin resistance). IPGTT was higher in T5 rats
      and directly correlated with body weight at prepubertal age. However, the
      decrease in the body weight at prepubertal age was compensated during adult life.
      Although both groups showed enhanced ovarian steroidogenesis, it appears that the
      molecular mechanisms involved were different. The higher dose of testosterone
      enhanced the expression of both the protein that regulates cholesterol
      availability (the steroidogenic acute regulatory protein (StAR)) and the protein
      expression of the transcriptional factor: peroxisome proliferator-activated
      receptor gamma (PPAR gamma). Prenatal hyperandrogenization induced an anti
      oxidant response that prevented a possible pro-oxidant status. The higher dose of
      testosterone induced a pro-inflammatory state in ovarian tissue mediated by
      increased levels of prostaglandin E (PG) and the protein expression of
      cyclooxygenase 2 (COX2, the limiting enzyme of PGs synthesis). In summary, our
      data show that the levels of testosterone prenatally injected modulate the
      uterine environment and that this, in turn, would be responsible for the
      endocrine and metabolic abnormalities and the phenotype of PCOS during the adult
      life.

PMID- 22655063
TI  - Transient B cell depletion or improved transgene expression by codon optimization
      promote tolerance to factor VIII in gene therapy.
AB  - The major complication in the treatment of hemophilia A is the development of
      neutralizing antibodies (inhibitors) against factor VIII (FVIII). The current
      method for eradicating inhibitors, termed immune tolerance induction (ITI), is
      costly and protracted. Clinical protocols that prevent rather than treat
      inhibitors are not yet established. Liver-directed gene therapy hopes to achieve
      long-term correction of the disease while also inducing immune tolerance. We
      sought to investigate the use of adeno-associated viral (serotype 8) gene
      transfer to induce tolerance to human B domain deleted FVIII in hemophilia A
      mice. We administered an AAV8 vector with either human B domain deleted FVIII or
      a codon-optimized transgene, both under a liver-specific promoter to two strains
      of hemophilia A mice. Protein therapy or gene therapy was given either alone or
      in conjunction with anti-CD20 antibody-mediated B cell depletion. Gene therapy
      with a low-expressing vector resulted in sustained near-therapeutic expression.
      However, supplementary protein therapy revealed that gene transfer had sensitized
      mice to hFVIII in a high-responder strain but not in mice of a low-responding
      strain. This heightened response was ameliorated when gene therapy was delivered
      with anti-murine CD20 treatment. Transient B cell depletion prevented inhibitor
      formation in protein therapy, but failed to achieve a sustained hypo
      responsiveness. Importantly, use of a codon-optimized hFVIII transgene resulted
      in sustained therapeutic expression and tolerance without a need for B cell
      depletion. Therefore, anti-CD20 may be beneficial in preventing vector-induced
      immune priming to FVIII, but higher levels of liver-restricted expression are
      preferred for tolerance.

PMID- 22655065
TI  - Risk factors of porcine cysticercosis in the Eastern Cape Province, South Africa.
AB  - There is a high prevalence of Taenia solium taeniosis/cysticercosis in humans and
      pigs in the Eastern Cape Province (ECP) of South Africa. The objective of this
      study was to identify risk factors of porcine cysticercosis in select districts
      of the ECP. Data were collected in 2003 by interviewing 217 pig producers from
      the area. Blood samples were collected from 261 of their pigs, which were tested
      using two enzyme-linked immunosorbent assays (ELISA) for the presence of
      antibodies to cysticercosis. Frequencies of both owner- and pig-level
      characteristics were determined. For pig-level analysis, all bivariable and
      multivariable associations were determined using the surveylogistic procedure of
      the SAS/STAT(r) software to accommodate for the intraclass correlation that
      exists for clusters of pigs within one owner and for clusters of owners within a
      district. All tests for significance were performed at the alpha = 0.05 level,
      and adjusted odds ratios (aOR) and 95% confidence intervals (CI) were determined.
      Among the respondents, 48% of their households lacked a latrine, 98% slaughtered
      pigs at home, and 99% indicated that meat inspection services were not available.
      On bivariable analysis, there was a significant association between porcine
      infection and district (p = 0.003), breed (p = 0.041) and the absence of a
      latrine (p = 0.006). On multivariable analysis, the absence of a latrine was the
      only variable significantly associated with porcine infection (aOR = 1.89; 95% CI
      = 1.07, 3.35) (p = 0.028). The increased odds of porcine infection with
      households lacking a latrine contributes to our understanding of the transmission
      of this parasite in the ECP. Determining and addressing the risk factors for T.
      solium infection can potentially lower the very high prevalence in humans and
      pigs in this endemic area.

PMID- 22655064
TI  - Differences in rat dorsal striatal NMDA and AMPA receptors following acute and
      repeated cocaine-induced locomotor activation.
AB  - Sprague-Dawley rats can be classified as low or high cocaine responders (LCRs or
      HCRs, respectively) based on their locomotor activity induced by an acute low
      dose of cocaine. Upon repeated cocaine exposure, LCRs display greater locomotor
      sensitization, reward, and reinforcement than HCRs. Altered glutamate receptor
      expression in the brain reward pathway has been linked to locomotor sensitization
      and addiction. To determine if such changes contribute to the differential
      development of locomotor sensitization, we examined protein levels of total,
      phosphorylated, and cell surface glutamate N-methyl D-aspartate (NMDA) and alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors (Rs) following
      acute or repeated cocaine (10 mg/kg, i.p.) in LCRs, HCRs and saline controls.
      Three areas involved in the development and expression of locomotor sensitization
      were investigated: the ventral tegmental area (VTA), nucleus accumbens (NAc) and
      dorsal striatum (dSTR). Our results revealed differences only in the dSTR, where
      we found that after acute cocaine, GluN2B(Tyr-1472) phosphorylation was
      significantly greater in LCRs, compared to HCRs and controls. Additionally in
      dSTR, after repeated cocaine, we observed significant increases in total GluA1,
      phosphorylated GluA1(Ser-845), and cell surface GluA1 in all cocaine-treated
      animals vs. controls. The acute cocaine-induced increases in NMDARs in dSTR of
      LCRs may help to explain the more ready development of locomotor sensitization
      and susceptibility to addiction-like behaviors in rats that initially exhibit
      little or no cocaine-induced activation, whereas the AMPAR increases after
      repeated cocaine may relate to recruitment of more dorsal striatal circuits and
      maintenance of the marked cocaine-induced locomotor activation observed in all of
      the rats.

PMID- 22655066
TI  - Nucleoprotein nanostructures combined with adjuvants adapted to the neonatal
      immune context: a candidate mucosal RSV vaccine.
AB  - BACKGROUND: The human respiratory syncytial virus (hRSV) is the leading cause of
      severe bronchiolitis in infants worldwide. The most severe RSV diseases occur
      between 2 and 6 months-of-age, so pediatric vaccination will have to be started
      within the first weeks after birth, when the immune system is prone to Th2
      responses that may turn deleterious upon exposure to the virus. So far, the high
      risk to prime for immunopathological responses in infants has hampered the
      development of vaccine. In the present study we investigated the safety and
      efficacy of ring-nanostructures formed by the recombinant nucleoprotein N of hRSV
      (N(SRS)) as a mucosal vaccine candidate against RSV in BALB/c neonates, which are
      highly sensitive to immunopathological Th2 imprinting. METHODOLOGY AND PRINCIPAL
      FINDINGS: A single intranasal administration of N(SRS) with detoxified E. coli
      enterotoxin LT(R192G) to 5-7 day old neonates provided a significant reduction of
      the viral load after an RSV challenge at five weeks of age. However, neonatal
      vaccination also generated an enhanced lung infiltration by neutrophils and
      eosinophils following the RSV challenge. Analysis of antibody subclasses and
      cytokines produced after an RSV challenge or a boost administration of the
      vaccine suggested that neonatal vaccination induced a Th2 biased local immune
      memory. This Th2 bias and the eosinophilic reaction could be prevented by adding
      CpG to the vaccine formulation, which, however did not prevent pulmonary
      inflammation and neutrophil infiltration upon viral challenge.
      CONCLUSIONS/SIGNIFICANCE: In conclusion, protective vaccination against RSV can
      be achieved in neonates but requires an appropriate combination of adjuvants to
      prevent harmful Th2 imprinting.

PMID- 22655067
TI  - Using bacterial extract along with differential gene expression in Acropora
      millepora larvae to decouple the processes of attachment and metamorphosis.
AB  - Biofilms of the bacterium Pseudoalteromonas induce metamorphosis of acroporid
      coral larvae. The bacterial metabolite tetrabromopyrrole (TBP), isolated from an
      extract of Pseudoalteromonas sp. associated with the crustose coralline alga
      (CCA) Neogoniolithon fosliei, induced coral larval metamorphosis (100%) with
      little or no attachment (0-2%). To better understand the molecular events and
      mechanisms underpinning the induction of Acropora millepora larval metamorphosis,
      including cell proliferation, apoptosis, differentiation, migration, adhesion and
      biomineralisation, two novel coral gene expression assays were implemented. These
      involved the use of reverse-transcriptase quantitative PCR (RT-qPCR) and employed
      47 genes of interest (GOI), selected based on putative roles in the processes of
      settlement and metamorphosis. Substantial differences in transcriptomic responses
      of GOI were detected following incubation of A. millepora larvae with a threshold
      concentration and 10-fold elevated concentration of TBP-containing extracts of
      Pseudoalteromonas sp. The notable and relatively abrupt changes of the larval
      body structure during metamorphosis correlated, at the molecular level, with
      significant differences (p<0.05) in gene expression profiles of 24 GOI, 12 hours
      post exposure. Fourteen of those GOI also presented differences in expression
      (p<0.05) following exposure to the threshold concentration of bacterial TBP
      containing extract. The specificity of the bacterial TBP-containing extract to
      induce the metamorphic stage in A. millepora larvae without attachment, using a
      robust, low cost, accurate, ecologically relevant and highly reproducible RT-qPCR
      assay, allowed partially decoupling of the transcriptomic processes of attachment
      and metamorphosis. The bacterial TBP-containing extract provided a unique
      opportunity to monitor the regulation of genes exclusively involved in the
      process of metamorphosis, contrasting previous gene expression studies that
      utilized cues, such as crustose coralline algae, biofilms or with GLW-amide
      neuropeptides that stimulate the entire onset of larval metamorphosis and
      attachment.

PMID- 22655068
TI  - Dissection of influenza A virus M1 protein: pH-dependent oligomerization of N
      terminal domain and dimerization of C-terminal domain.
AB  - BACKGROUND: The matrix 1 (M1) protein of Influenza A virus plays many critical
      roles throughout the virus life cycle. The oligomerization of M1 is essential for
      the formation of the viral matrix layer during the assembly and budding process.
      METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we report that M1 can
      oligomerize in vitro, and that the oligomerization is pH-dependent. The N
      terminal domain of M1 alone exists as multiple-order oligomers at pH 7.4, and the
      C-terminal domain alone forms an exclusively stable dimer. As a result, intact M1
      can display different forms of oligomers and dimer is the smallest
      oligomerization state, at neutral pH. At pH 5.0, oligomers of the N-terminal
      domain completely dissociate into monomers, while the C-terminal domain remains
      in dimeric form. As a result, oligomers of intact M1 dissociate into a stable
      dimer at acidic pH. CONCLUSIONS/SIGNIFICANCE: Oligomerization of M1 involves both
      the N- and C-terminal domains. The N-terminal domain determines the pH-dependent
      oligomerization characteristic, and C-terminal domain forms a stable dimer, which
      contributes to the dimerization of M1. The present study will help to unveil the
      mechanisms of influenza A virus assembly and uncoating process.

PMID- 22655069
TI  - IL-12 and GM-CSF in DNA/MVA immunizations against HIV-1 CRF12_BF Nef induced T
      cell responses with an enhanced magnitude, breadth and quality.
AB  - In Argentina, the HIV epidemic is characterized by the co-circulation of subtype
      B and BF recombinant viral variants. Nef is an HIV protein highly variable among
      subtypes, making it a good tool to study the impact of HIV variability in the
      vaccine design setting. We have previously reported a specific cellular response
      against NefBF with low cross-reactivity to NefB in mice. The aim of this work was
      to analyze whether the co-administration of IL-12 and GM-CSF, using DNA and MVA
      vaccine vectors, could improve the final cellular response induced. Mice received
      three DNA priming doses of a plasmid that express NefBF plus DNAs expressing IL
      12 and/or GM-CSF. Afterwards, all the groups were boosted with a MVAnefBF dose.
      The highest increase in the magnitude of the NefBF response, compared to that
      induced in the control was found in the IL-12 group. Importantly, a response with
      higher breadth was detected in groups which received IL-12 or GM-CSF, evidenced
      as an increased frequency of recognition of homologous (BF) and heterologous (B)
      Nef peptides, as well as a higher number of other Nef peptide pools representing
      different viral subtypes. However, these improvements were lost when both DNA
      cytokines were simultaneously administered, as the response was focused against
      the immunodominant peptide with a detrimental response towards subdominant
      epitopes. The pattern of cytokines secreted and the specific-T-cell proliferative
      capacity were improved in IL-12 and IL-12+GM-CSF groups. Importantly IL-12
      generated a significant higher T-cell avidity against a B heterologous
      peptide.This study indicates that the incorporation of DNA expressing IL-12 in
      DNA/MVA schemes produced the best results in terms of improvements of T-cell
      response key properties such as breadth, cross-reactivity and quality (avidity
      and pattern of cytokines secreted). These relevant results contribute to the
      design of strategies aimed to induce T-cell responses against HIV antigens with
      higher quality.

PMID- 22655070
TI  - Carbon nanotube solar cells.
AB  - We present proof-of-concept all-carbon solar cells. They are made of a
      photoactive side of predominantly semiconducting nanotubes for photoconversion
      and a counter electrode made of a natural mixture of carbon nanotubes or
      graphite, connected by a liquid electrolyte through a redox reaction. The cells
      do not require rare source materials such as In or Pt, nor high-grade
      semiconductor processing equipment, do not rely on dye for photoconversion and
      therefore do not bleach, and are easy to fabricate using a spray-paint technique.
      We observe that cells with a lower concentration of carbon nanotubes on the
      active semiconducting electrode perform better than cells with a higher
      concentration of nanotubes. This effect is contrary to the expectation that a
      larger number of nanotubes would lead to more photoconversion and therefore more
      power generation. We attribute this to the presence of metallic nanotubes that
      provide a short for photo-excited electrons, bypassing the load. We demonstrate
      optimization strategies that improve cell efficiency by orders of magnitude. Once
      it is possible to make semiconducting-only carbon nanotube films, that may
      provide the greatest efficiency improvement.

PMID- 22655071
TI  - Comparison of ion balance and nitrogen metabolism in old and young leaves of
      alkali-stressed rice plants.
AB  - BACKGROUND: Alkali stress is an important agricultural contaminant and has
      complex effects on plant metabolism. The aim of this study was to investigate
      whether the alkali stress has different effects on the growth, ion balance, and
      nitrogen metabolism in old and young leaves of rice plants, and to compare
      functions of both organs in alkali tolerance. METHODOLOGY/PRINCIPAL FINDINGS: The
      results showed that alkali stress only produced a small effect on the growth of
      young leaves, whereas strongly damaged old leaves. Rice protected young leaves
      from ion harm via the large accumulation of Na(+) and Cl(-) in old leaves. The up
      regulation of OsHKT1;1, OsAKT1, OsHAK1, OsHAK7, OsHAK10 and OsHAK16 may
      contribute to the larger accumulation of Na(+) in old leaves under alkali stress.
      Alkali stress mightily reduced the NO(3)(-) contents in both organs. As old leaf
      cells have larger vacuole, under alkali stress these scarce NO(3)(-) was
      principally stored in old leaves. Accordingly, the expression of OsNRT1;1 and
      OsNRT1;2 in old leaves was up-regulated by alkali stress, revealing that the two
      genes might contribute to the accumulation of NO(3)(-) in old leaves. NO(3)(-)
      deficiency in young leaves under alkali stress might induce the reduction in
      OsNR1 expression and the subsequent lacking of NH(4)(+), which might be main
      reason for the larger down-regulation of OsFd-GOGAT and OsGS2 in young leaves.
      CONCLUSIONS/SIGNIFICANCE: Our results strongly indicated that, during adaptation
      of rice to alkali stress, young and old leaves have distinct mechanisms of ion
      balance and nitrogen metabolism regulation. We propose that the comparative
      studies of young and old tissues may be important for abiotic stress tolerance
      research.

PMID- 22655072
TI  - Dvl2-dependent activation of Daam1 and RhoA regulates Wnt5a-induced breast cancer
      cell migration.
AB  - BACKGROUND: The Dishevelled (Dvl) and Dishevelled-associated activator of
      morphogenesis 1 (Daam1) pathway triggered by Wnt5a regulates cellular polarity
      during development and tissue homoeostasis. However, Wnt5a signaling in breast
      cancer progression remains poorly defined. METHODOLOGY/PRINCIPAL FINDINGS: We
      showed here that Wnt5a activated Dvl2, Daam1 and RhoA, and promoted migration of
      breast cancer cells, which was, however, abolished by Secreted Frizzled-related
      protein 2 (sFRP2) pretreatment. Dominant negative Dvl2 mutants or Dvl2 siRNA
      significantly decreased Wnt5a-induced Daam1/RhoA activation and cell migration.
      Ectopic expression of N-Daam1, a dominant negative mutant, or Daam1 siRNA
      remarkably inhibited Wnt5a-induced RhoA activation, stress fiber formation and
      cell migration. Ectopic expression of dominant negative RhoA (N19) or C3
      exoenzyme transferase, a Rho inhibitor, decreased Wnt5a-induced stress fiber
      formation and cell migration. CONCLUSIONS/SIGNIFICANCE: Taken together, we
      demonstrated for the first time that Wnt5a promotes breast cancer cell migration
      via Dvl2/Daam1/RhoA.

PMID- 22655073
TI  - Evolutionary and experimental assessment of novel markers for detection of
      Xanthomonas euvesicatoria in plant samples.
AB  - BACKGROUND: Bacterial spot-causing xanthomonads (BSX) are quarantine
      phytopathogenic bacteria responsible for heavy losses in tomato and pepper
      production. Despite the research on improved plant spraying methods and resistant
      cultivars, the use of healthy plant material is still considered as the most
      effective bacterial spot control measure. Therefore, rapid and efficient
      detection methods are crucial for an early detection of these phytopathogens.
      METHODOLOGY: In this work, we selected and validated novel DNA markers for
      reliable detection of the BSX Xanthomonas euvesicatoria (Xeu). Xeu-specific DNA
      regions were selected using two online applications, CUPID and Insignia.
      Furthermore, to facilitate the selection of putative DNA markers, a customized C
      program was designed to retrieve the regions outputted by both databases. The in
      silico validation was further extended in order to provide an insight on the
      origin of these Xeu-specific regions by assessing chromosomal location, GC
      content, codon usage and synteny analyses. Primer-pairs were designed for
      amplification of those regions and the PCR validation assays showed that most
      primers allowed for positive amplification with different Xeu strains. The
      obtained amplicons were labeled and used as probes in dot blot assays, which
      allowed testing the probes against a collection of 12 non-BSX Xanthomonas and 23
      other phytopathogenic bacteria. These assays confirmed the specificity of the
      selected DNA markers. Finally, we designed and tested a duplex PCR assay and an
      inverted dot blot platform for culture-independent detection of Xeu in infected
      plants. SIGNIFICANCE: This study details a selection strategy able to provide a
      large number of Xeu-specific DNA markers. As demonstrated, the selected markers
      can detect Xeu in infected plants both by PCR and by hybridization-based assays
      coupled with automatic data analysis. Furthermore, this work is a contribution to
      implement more efficient DNA-based methods of bacterial diagnostics.

PMID- 22655074
TI  - Phylogeography and molecular evolution of potato virus Y.
AB  - Potato virus Y (PVY) is an important plant pathogen, whose host range includes
      economically important crops such as potato, tobacco, tomato, and pepper. PVY
      presents three main strains (PVY(O), PVY(N) and PVY(C)) and several recombinant
      forms. PVY has a worldwide distribution, yet the mechanisms that promote and
      maintain its population structure and genetic diversity are still unclear. In
      this study, we used a pool of 77 complete PVY genomes from isolates collected
      worldwide. After removing the effect of recombination in our data set, we used
      bayesian techniques to study the influence of geography and host species in both
      PVY population structure and dynamics. We have also performed selection and
      covariation analyses to identify evolutionarily relevant amino acid residues. Our
      results show that both geographic and host-driven adaptations explain PVY
      diversification. Furthermore, purifying selection is the main force driving PVY
      evolution, although some indications of positive selection accounted for the
      diversification of the different strains. Interestingly, the analysis of P3N
      PIPO, a recently described gene in potyviruses, seems to show a variable length
      among the isolates analyzed, and this variability is explained, in part, by host
      driven adaptation.

PMID- 22655075
TI  - Improved somatic mutagenesis in zebrafish using transcription activator-like
      effector nucleases (TALENs).
AB  - Zinc Finger Nucleases (ZFNs) made by Context-Dependent Assembly (CoDA) and
      Transcription Activator-Like Effector Nucleases (TALENs) provide robust and user
      friendly technologies for efficiently inactivating genes in zebrafish. These
      designer nucleases bind to and cleave DNA at particular target sites, inducing
      error-prone repair that can result in insertion or deletion mutations. Here, we
      assess the relative efficiencies of these technologies for inducing somatic DNA
      mutations in mosaic zebrafish. We find that TALENs exhibited a higher success
      rate for obtaining active nucleases capable of inducing mutations than compared
      with CoDA ZFNs. For example, all six TALENs tested induced DNA mutations at
      genomic target sites while only a subset of CoDA ZFNs exhibited detectable rates
      of mutagenesis. TALENs also exhibited higher mutation rates than CoDA ZFNs that
      had not been pre-screened using a bacterial two-hybrid assay, with DNA mutation
      rates ranging from 20%-76.8% compared to 1.1%-3.3%. Furthermore, the broader
      targeting range of TALENs enabled us to induce mutations at the methionine
      translation start site, sequences that were not targetable using the CoDA ZFN
      platform. TALENs exhibited similar toxicity to CoDA ZFNs, with >50% of injected
      animals surviving to 3 days of life. Taken together, our results suggest that
      TALEN technology provides a robust alternative to CoDA ZFNs for inducing targeted
      gene-inactivation in zebrafish, making it a preferred technology for creating
      targeted knockout mutants in zebrafish.

PMID- 22655076
TI  - Reconsideration of in-silico siRNA design based on feature selection: a cross
      platform data integration perspective.
AB  - RNA interference via exogenous short interference RNAs (siRNA) is increasingly
      more widely employed as a tool in gene function studies, drug target discovery
      and disease treatment. Currently there is a strong need for rational siRNA design
      to achieve more reliable and specific gene silencing; and to keep up with the
      increasing needs for a wider range of applications. While progress has been made
      in the ability to design siRNAs with specific targets, we are clearly at an
      infancy stage towards achieving rational design of siRNAs with high efficacy.
      Among the many obstacles to overcome, lack of general understanding of what
      sequence features of siRNAs may affect their silencing efficacy and of large
      scale homogeneous data needed to carry out such association analyses represents
      two challenges. To address these issues, we investigated a feature-selection
      based in-silico siRNA design from a novel cross-platform data integration
      perspective. An integration analysis of 4,482 siRNAs from ten meta-datasets was
      conducted for ranking siRNA features, according to their possible importance to
      the silencing efficacy of siRNAs across heterogeneous data sources. Our ranking
      analysis revealed for the first time the most relevant features based on cross
      platform experiments, which compares favorably with the traditional in-silico
      siRNA feature screening based on the small samples of individual platform data.
      We believe that our feature ranking analysis can offer more creditable
      suggestions to help improving the design of siRNA with specific silencing
      targets. Data and scripts are available at
      http://csbl.bmb.uga.edu/publications/materials/qiliu/siRNA.html.

PMID- 22655077
TI  - West Nile virus infection causes endocytosis of a specific subset of tight
      junction membrane proteins.
AB  - West Nile virus (WNV) is a blood-borne pathogen that causes systemic infections
      and serious neurological disease in human and animals. The most common route of
      infection is mosquito bites and therefore, the virus must cross a number of
      polarized cell layers to gain access to organ tissue and the central nervous
      system. Resistance to trans-cellular movement of macromolecules between
      epithelial and endothelial cells is mediated by tight junction complexes. While a
      number of recent studies have documented that WNV infection negatively impacts
      the barrier function of tight junctions, the intracellular mechanism by which
      this occurs is poorly understood. In the present study, we report that
      endocytosis of a subset of tight junction membrane proteins including claudin-1
      and JAM-1 occurs in WNV infected epithelial and endothelial cells. This process,
      which ultimately results in lysosomal degradation of the proteins, is dependent
      on the GTPase dynamin and microtubule-based transport. Finally, infection of
      polarized cells with the related flavivirus, Dengue virus-2, did not result in
      significant loss of tight junction membrane proteins. These results suggest that
      neurotropic flaviviruses such as WNV modulate the host cell environment
      differently than hemorrhagic flaviviruses and thus may have implications for
      understanding the molecular basis for neuroinvasion.

PMID- 22655078
TI  - Professional exposure to goats increases the risk of pneumonic-type lung
      adenocarcinoma: results of the IFCT-0504-Epidemio study.
AB  - Pneumonic-type lung adenocarcinoma (P-ADC) represents a distinct subset of lung
      cancer with specific clinical, radiological, and pathological features. Given the
      weak association with tobacco-smoking and the striking similarities with
      jaagsiekte sheep retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma, it has
      been suggested that a zoonotic viral agent infecting pulmonary cells may
      predispose to P-ADC in humans. Our objective was to explore whether exposure to
      domestic small ruminants may represent a risk factor for P-ADC. We performed a
      multicenter case-control study recruiting patients with P-ADC as cases and
      patients with non-P-ADC non-small cell lung cancer as controls. A dedicated 356
      item questionnaire was built to evaluate exposure to livestock. A total of 44
      cases and 132 controls were included. At multivariate analysis, P-ADC was
      significantly more associated with female gender (Odds-ratio (OR) = 3.23, 95%
      confidence interval (CI): 1.32-7.87, p = 0.010), never-smoker status (OR = 3.57,
      95% CI: 1.27-10.00, p = 0.015), personal history of extra-thoracic cancer before
      P-ADC diagnosis (OR = 3.43, 95% CI: 1.10-10.72, p = 0.034), and professional
      exposure to goats (OR = 5.09, 95% CI: 1.05-24.69, p = 0.043), as compared to
      other subtypes of lung cancer. This case-control suggests a link between
      professional exposure to goats and P-ADC, and prompts for further epidemiological
      evaluation of potential environmental risk factors for P-ADC.

PMID- 22655079
TI  - Spatio-temporal patterns of key exploited marine species in the Northwestern
      Mediterranean Sea.
AB  - This study analyzes the temporal variability/stability of the spatial
      distributions of key exploited species in the Gulf of Lions (Northwestern
      Mediterranean Sea). To do so, we analyzed data from the MEDITS bottom-trawl
      scientific surveys from 1994 to 2010 at 66 fixed stations and selected 12 key
      exploited species. We proposed a geostatistical approach to handle zero-inflated
      and non-stationary distributions and to test for the temporal stability of the
      spatial structures. Empirical Orthogonal Functions and other descriptors were
      then applied to investigate the temporal persistence and the characteristics of
      the spatial patterns. The spatial structure of the distribution (i.e. the pattern
      of spatial autocorrelation) of the 12 key species studied remained highly stable
      over the time period sampled. The spatial distributions of all species obtained
      through kriging also appeared to be stable over time, while each species
      displayed a specific spatial distribution. Furthermore, adults were generally
      more densely concentrated than juveniles and occupied areas included in the
      distribution of juveniles. Despite the strong persistence of spatial
      distributions, we also observed that the area occupied by each species was
      correlated to its abundance: the more abundant the species, the larger the
      occupation area. Such a result tends to support MacCall's basin theory, according
      to which density-dependence responses would drive the expansion of those 12 key
      species in the Gulf of Lions. Further analyses showed that these species never
      saturated their habitats, suggesting that they are below their carrying capacity;
      an assumption in agreement with the overexploitation of several of these species.
      Finally, the stability of their spatial distributions over time and their
      potential ability to diffuse outside their main habitats give support to Marine
      Protected Areas as a potential pertinent management tool.

PMID- 22655080
TI  - Role of c-Jun N-terminal protein kinase 1/2 (JNK1/2) in macrophage-mediated MMP-9
      production in response to Moraxella catarrhalis lipooligosaccharide (LOS).
AB  - Moraxella catarrhalis is a gram negative bacterium and a leading causative agent
      of otitis media (OM) in children. Recent reports have provided strong evidence
      for the presence of high levels of matrix metalloproteinase (MMPs) in effusion
      fluids from children suffering with OM, however, the precise mechanisms by which
      MMPs are generated are currently unknown. We hypothesized that MMPs are secreted
      from macrophages in the presence of M. catarrhalis lipooligosaccharide (LOS). In
      this report, we demonstrate that in vitro stimulation of murine macrophage RAW
      264.7 cells with LOS leads to secretion of MMP-9 as determined by ELISA and
      zymogram assays. We have also shown that inhibition of ERK1/2 and p38 kinase
      completely blocked LOS induced MMP-9 production. In contrast, inhibition of
      JNK1/2 by the specific inhibitor SP600125 actually increased the level of
      expression and production of MMP-9 at both mRNA and protein levels, respectively
      by almost five fold. This latter result was confirmed by knocking down JNK1/2
      using siRNA. Similar results have been observed in murine bone marrow derived
      macrophages in vitro. In contrast to and in parallel with the LOS-induced
      increased levels of MMP-9 in the presence of SP600125, we found a corresponding
      dose-dependent inhibition of TIMP-1 (tissue inhibitor of matrix metalloproteinase
      1) secretion. Results of subsequent in vitro studies provided evidence that when
      JNK1/2 was inhibited prior to stimulation with LOS, it significantly increased
      both the extent of macrophage cell migration and invasion compared to control
      cells or cells treated with LOS alone. The results of these studies contribute to
      an increased understanding of the underlying pathophysiology of OM with effusion
      in children.

PMID- 22655081
TI  - Identification and characterisation of a novel acylpeptide hydrolase from
      Sulfolobus solfataricus: structural and functional insights.
AB  - A novel acylpeptide hydrolase, named APEH-3(Ss), was isolated from the
      hypertermophilic archaeon Sulfolobus solfataricus. APEH is a member of the prolyl
      oligopeptidase family which catalyzes the removal of acetylated amino acid
      residues from the N terminus of oligopeptides. The purified enzyme shows a
      homotrimeric structure, unique among the associate partners of the APEH cluster
      and, in contrast to the archaeal APEHs which show both exo/endo peptidase
      activities, it appears to be a "true" aminopeptidase as exemplified by its
      mammalian counterparts, with which it shares a similar substrate specificity.
      Furthermore, a comparative study on the regulation of apeh gene expression,
      revealed a significant but divergent alteration in the expression pattern of apeh
      3(Ss) and apeh(Ss) (the gene encoding the previously identified APEH(Ss) from S.
      solfataricus), which is induced in response to various stressful growth
      conditions. Hence, both APEH enzymes can be defined as stress-regulated proteins
      which play a complementary role in enabling the survival of S. solfataricus cells
      under different conditions. These results provide new structural and functional
      insights into S. solfataricus APEH, offering a possible explanation for the
      multiplicity of this enzyme in Archaea.

PMID- 22655083
TI  - Heat shock factor 1 contributes to ischemia-induced angiogenesis by regulating
      the mobilization and recruitment of bone marrow stem/progenitor cells.
AB  - Bone marrow (BM)-derived stem/progenitor cells play an important role in ischemia
      induced angiogenesis in cardiovascular diseases. Heat shock factor 1 (HSF1) is
      known to be induced in response to hypoxia and ischemia. We examined whether HSF1
      contributes to ischemia-induced angiogenesis through the mobilization and
      recruitment of BM-derived stem/progenitor cells using HSF1-knockout (KO) mice.
      After the induction of ischemia, blood flow and microvessel density in the
      ischemic hindlimb were significantly lower in the HSF1-KO mice than in the wild
      type (WT) mice. The mobilization of BM-derived Sca-1- and c-kit-positive cells in
      peripheral blood after ischemia was significantly lower in the HSF1-KO mice than
      in the WT mice. BM stem/progenitor cells from HSF1-KO mice showed a significant
      decrease in their recruitment to ischemic tissue and in migration, adhesion, and
      survival when compared with WT mice. Blood flow recovery in the ischemic hindlimb
      significantly decreased in WT mice receiving BM reconstitution with donor cells
      from HSF1-KO mice. Conversely, blood flow recovery in the ischemic hindlimb
      significantly increased in HSF1-KO mice receiving BM reconstitution with donor
      cells from WT mice. These findings suggest that HSF1 contributes to ischemia
      induced angiogenesis by regulating the mobilization and recruitment of BM-derived
      stem/progenitor cells.

PMID- 22655082
TI  - Host immune responses to a viral immune modulating protein: immunogenicity of
      viral interleukin-10 in rhesus cytomegalovirus-infected rhesus macaques.
AB  - BACKGROUND: Considerable evidence has accumulated that multiple viruses,
      bacteria, and protozoa manipulate interleukin-10 (IL-10)-mediated signaling
      through the IL-10 receptor (IL-10R) in ways that could enable establishment of a
      persistent microbial infection. This suggests that inhibition of pathogen
      targeting of IL-10/IL-10R signaling could prevent microbial persistence. Human
      cytomegalovirus (HCMV) and rhesus cytomegalovirus (RhCMV) express a viral
      interleukin-10 (cmvIL-10 and rhcmvIL-10, respectively) with comparable immune
      modulating properties in vitro to that of their host's cellular IL-10 (cIL-10). A
      prior study noted that rhcmvIL-10 alters innate and adaptive immunity to RhCMV in
      vivo, consistent with a central role for rhcmvIL-10 during acute virus-host
      interactions. Since cmvIL-10 and rhcmvIL-10 are extremely divergent from the cIL
      10 of their respective hosts, vaccine-mediated neutralization of their function
      could inhibit establishment of viral persistence without inhibition of cIL-10.
      METHODS AND FINDINGS: As a prelude to evaluating cmvIL-10-based vaccines in
      humans, the rhesus macaque model of HCMV was used to interrogate peripheral and
      mucosal immune responses to rhcmvIL-10 in RhCMV-infected animals. ELISA were used
      to detect rhcmvIL-10-binding antibodies in plasma and saliva, and an IL-12-based
      bioassay was used to quantify plasma antibodies that neutralized rhcmvIL-10
      function. rhcmvIL-10 is highly immunogenic during RhCMV infection, stimulating
      high avidity rhcmvIL-10-binding antibodies in the plasma of all infected animals.
      Most infected animals also exhibited plasma antibodies that partially neutralized
      rhcmvIL-10 function but did not cross-neutralize the function of rhesus cIL-10.
      Notably, minimally detectable rhcmvIL-10-binding antibodies were detected in
      saliva. CONCLUSION: This study demonstrates that rhcmvIL-10, as a surrogate for
      cmvIL-10, is a viable vaccine candidate because (1) it is highly immunogenic
      during natural RhCMV infection, and (2) neutralizing antibodies to rhcmvIL-10 do
      not cross-react with rhesus cIL-10. Exceedingly low rhcmvIL-10 antibodies in
      saliva further suggest that the oral mucosa, which is critical in RhCMV natural
      history, is associated with suboptimal anti-rhcmvIL-10 antibody responses.

PMID- 22655085
TI  - Circadian rhythm-dependent alterations of gene expression in Drosophila brain
      lacking fragile X mental retardation protein.
AB  - Fragile X syndrome is caused by the loss of the FMR1 gene product, fragile X
      mental retardation protein (FMRP). The loss of FMRP leads to altered circadian
      rhythm behaviors in both mouse and Drosophila; however, the molecular mechanism
      behind this phenomenon remains elusive. Here we performed a series of gene
      expression analyses, including of both mRNAs and microRNAs (miRNAs), and
      identified a number of mRNAs and miRNAs (miRNA-1 and miRNA-281) with circadian
      rhythm-dependent altered expression in dfmr1 mutant flies. Identification of
      these RNAs lays the foundation for future investigations of the molecular
      pathway(s) underlying the altered circadian rhythms associated with loss of
      dFmr1.

PMID- 22655084
TI  - Combination of RGD compound and low-dose paclitaxel induces apoptosis in human
      glioblastoma cells.
AB  - BACKGROUND: Integrins are a family of transmembrane adhesion proteins that
      mediate cell adhesion and intracellular signaling. Integrin-alphavbeta3 is
      expressed on the surface of human glioblastoma cells, and can be further induced
      by chemical stress. The Arg-Gly-Asp (RGD) motif-containing peptides are
      specifically bound to integrin-alphavbeta3, and to inhibit neovasculature
      underlying competition to normal extracellular matrix proteins. This study
      employed two types of RGD peptides, cyclic RGD (c(RGDyK)) and bi-cyclic RGD
      (E[c(RGDyK)](2)) peptide, to human glioblastoma U87MG cells with combination of
      low dose Paclitaxel (PTX) pre-treatment to augment therapeutic activity for RGD
      peptide-induced apoptosis. PRINCIPAL FINDINGS: Human glioblastoma U87MG cells
      were treated with RGD peptides in the absence or presence of initial exposure to
      low-dose 10 nM PTX. Results showed that integrin-alphavbeta3 expressing on the
      surface of U87MG cells was induced by 10 nM PTX pre-treatment for 12 hrs.
      Additionally, the U87MG cells pre-treated with PTX and followed by RGD peptides
      exhibited greater expression of caspases-3, -8 and -9 than those merely treated
      with single agent of PTX or RGD peptide. Furthermore, the caspase-3, -8 and -9
      inhibitor presented significant protection against E[c(RGDyK)](2) peptide induced
      U87MG programmed cell death. The increased expression of PTX-induced integrin
      alphavbeta3 was correlated with the enhanced apoptosis in U87MG cells.
      CONCLUSIONS: This study provides a novel concept of targeting integrin
      alphavbeta3 with RGD peptides in combination with low-dose PTX pre-treatment to
      improve efficiency in human glioblastoma treatment.

PMID- 22655086
TI  - Minimally invasive surgical approaches and traditional total hip arthroplasty: a
      meta-analysis of radiological and complications outcomes.
AB  - BACKGROUND: Minimally invasive total hip arthroplasty (MITHA) remains
      considerably controversial. Limited visibility and prosthesis malposition
      increase the risk of post-surgical complications compared to those of the
      traditional method. METHODS: A meta-analysis was undertaken of all published
      databases up to May 2011. The studies were divided into four subgroups according
      to the surgical approach taken. The radiological outcomes and complications of
      minimally invasive surgery were compared to traditional total hip arthroplasty
      (TTHA) using risk ratio, mean difference, and standardized mean difference
      statistics. RESULTS: In five studies involving the posterolateral approach, no
      significant differences were found between the MITHA groups and the TTHA groups
      in the acetabular cup abduction angle (p = 0.41), acetabular anteversion (p =
      0.96), and femoral prosthesis position (p = 0.83). However, the femoral offset
      was significantly increased (WMD = 3.00; 95% CI, 0.40-5.60; p = 0.02).
      Additionally, there were no significant differences among the complications in
      both the groups (dislocations, nerve injury, infection, deep vein thrombosis,
      proximal femoral fracture) and revision rate (p>0.05). In three studies involving
      the posterior approach, there were no significant differences in radiological
      outcomes or all other complications between MITHA or TTHA groups (p>0.05). Three
      studies involved anterolateral approach, while 2 studies used the lateral
      approach. However, the information from imaging and complications was not
      adequate for statistical analysis. CONCLUSIONS: Posterior MITHA seems to be a
      safe surgical procedure, without the increased risk of post-operative
      complication rates and component malposition rates. The posterolateral approach
      THA may lead to increased femoral offset. The current data are not enough to
      reach a positive conclusion that lateral and anterolateral approaches will result
      in increased risks of adverse effects and complications at the prosthesis site.

PMID- 22655087
TI  - Nonlinear optical microscopy for histology of fresh normal and cancerous
      pancreatic tissues.
AB  - BACKGROUND: Pancreatic cancer is a lethal disease with a 5-year survival rate of
      only 1-5%. The acceleration of intraoperative histological examination would be
      beneficial for better management of pancreatic cancer, suggesting an improved
      survival. Nonlinear optical methods based on two-photon excited fluorescence
      (TPEF) and second harmonic generation (SHG) of intrinsic optical biomarkers show
      the ability to visualize the morphology of fresh tissues associated with
      histology, which is promising for real-time intraoperative evaluation of
      pancreatic cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate
      whether the nonlinear optical imaging methods have the ability to characterize
      pancreatic histology at cellular resolution, we studied different types of
      pancreatic tissues by using label-free TPEF and SHG. Compared with other routine
      methods for the preparation of specimens, fresh tissues without processing were
      found to be most suitable for nonlinear optical imaging of pancreatic tissues.
      The detailed morphology of the normal rat pancreas was observed and related with
      the standard histological images. Comparatively speaking, the preliminary images
      of a small number of chemical-induced pancreatic cancer tissues showed visible
      neoplastic differences in the morphology of cells and extracellular matrix. The
      subcutaneous pancreatic tumor xenografts were further observed using the
      nonlinear optical microscopy, showing that most cells are leucocytes at 5 days
      after implantation, the tumor cells begin to proliferate at 10 days after
      implantation, and the extracellular collagen fibers become disordered as the
      xenografts grow. CONCLUSIONS/SIGNIFICANCE: In this study, nonlinear optical
      imaging was used to characterize the morphological details of fresh pancreatic
      tissues for the first time. We demonstrate that it is possible to provide real
      time histological evaluation of pancreatic cancer by the nonlinear optical
      methods, which present an opportunity for the characterization of the progress of
      spontaneous pancreatic cancer and further application in a non-invasive manner.

PMID- 22655088
TI  - Human papillomavirus type 18 E6 and E7 genes integrate into human hepatoma
      derived cell line Hep G2.
AB  - BACKGROUND AND OBJECTIVES: Human papillomaviruses have been linked causally to
      some human cancers such as cervical carcinoma, but there is very little research
      addressing the effect of HPV infection on human liver cells. We chose the human
      hepatoma derived cell line Hep G2 to investigate whether HPV gene integration
      took place in liver cells as well. METHODS: We applied PCR to detect the possible
      integration of HPV genes in Hep G2 cells. We also investigated the expression of
      the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we
      silenced E6 and E7 expression and checked the cell proliferation and apoptosis in
      Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle
      and apoptosis regulatory pathways. Finally, we used in situ hybridization to
      detect HPV 16/18 in hepatocellular carcinoma samples. RESULTS: Hep G2 cell line
      contains integrated HPV 18 DNA, leading to the expression of the E6 and E7
      oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell
      proliferation, caused the cell cycle arrest at the S phase, and increased
      apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis
      demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1,
      E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of
      patients with hepatocellular carcinoma. CONCLUSION: Our investigations showed
      that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a
      low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the
      precise risk of HPV as causative agent of hepatocellular carcinoma needs further
      study.

PMID- 22655089
TI  - Multimodal communication in a noisy environment: a case study of the Bornean rock
      frog Staurois parvus.
AB  - High background noise is an impediment to signal detection and perception. We
      report the use of multiple solutions to improve signal perception in the acoustic
      and visual modality by the Bornean rock frog, Staurois parvus. We discovered that
      vocal communication was not impaired by continuous abiotic background noise
      characterised by fast-flowing water. Males modified amplitude, pitch, repetition
      rate and duration of notes within their advertisement call. The difference in
      sound pressure between advertisement calls and background noise at the call
      dominant frequency of 5578 Hz was 8 dB, a difference sufficient for receiver
      detection. In addition, males used several visual signals to communicate with
      conspecifics with foot flagging and foot flashing being the most common and
      conspicuous visual displays, followed by arm waving, upright posture, crouching,
      and an open-mouth display. We used acoustic playback experiments to test the
      efficacy-based alerting signal hypothesis of multimodal communication. In support
      of the alerting hypothesis, we found that acoustic signals and foot flagging are
      functionally linked with advertisement calling preceding foot flagging. We
      conclude that S. parvus has solved the problem of continuous broadband low
      frequency noise by both modifying its advertisement call in multiple ways and by
      using numerous visual signals. This is the first example of a frog using multiple
      acoustic and visual solutions to communicate in an environment characterised by
      continuous noise.

PMID- 22655091
TI  - Autonomic function following acute organophosphorus poisoning: a cohort study.
AB  - Autonomic dysfunction after chronic low level exposure to organophosphorus (OP)
      pesticides has been consistently reported in the literature, but not following a
      single acute overdose. In order to study autonomic function after an acute OP
      overdose, sixty-six overdose patients were compared to 70 matched controls.
      Assessment of autonomic function was done by heart rate response to standing,
      deep breathing (HR-DB) and Valsalva manoeuvre; blood pressure (BP) response to
      standing and sustained hand grip; amplitude and latency of sympathetic skin
      response (SSR); pupil size and post-void urine volume. The patients were assessed
      one and six weeks after the exposure. The number of patients who showed abnormal
      autonomic function compared to standard cut-off values did not show statistically
      significantly difference from that of controls by Chi-Square test. When compared
      to the controls at one week the only significant differences consistent with
      autonomic dysfunction were change of diastolic BP 3 min after standing, HR-DB,
      SSR-Amplitude, SSR-Latency, post-void urine volume and size of the pupil. At 6
      weeks significant recovery of autonomic function was observed and only HR-DB was
      decreased to a minor degree, -5 beats/min [95%CI 2-8]. This study provides good
      evidence for the lack of long term autonomic dysfunction following acute exposure
      to OP pesticides.

PMID- 22655090
TI  - ATP-binding cassette transporter G5 and G8 polymorphisms and several
      environmental factors with serum lipid levels.
AB  - BACKGROUND: The association of ATP-binding cassette (ABC) transporter single
      nucleotide polymorphisms (SNPs) and serum lipid profiles is inconsistent. The
      present study was undertaken to detect the association of ABCG5/G8 SNPs and
      several environmental factors with serum lipid levels. METHODOLOGY/PRINCIPAL
      FINDINGS: Genotyping of the ABCG5 (rs4131229 and rs6720173) and ABCG8 (rs3806471
      and rs4148211) SNPs was performed in 719 unrelated subjects of Mulao nationality
      and 782 participants of Han nationality. There were no differences in the
      genotypic and allelic frequencies of four SNPs between the two ethnic groups
      besides the genotypic frequencies of rs4131229 SNP in Han. The levels of
      triglyceride (TG), apolipoprotein (Apo) A1, and ApoA1/ApoB ratio (rs4131229); low
      density lipoprotein cholesterol (LDL-C) and ApoB (rs6720173); high-density
      lipoprotein cholesterol (HDL-C), ApoA1, ApoB, and ApoA1/ApoB ratio (rs3806471);
      and HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han were different among
      their genotypes (P<0.05-0.001). The levels of LDL-C (rs6720173) and ApoA1
      (rs3806471) in Mulao were also different among their genotypes (P<0.05 for each).
      The levels of TC, TG, HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4131229); LDL-C and
      ApoB (rs6720173); HDL-C, ApoA1, and ApoA1/ApoB ratio (rs3806471); and TG, HDL-C,
      ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han males; and ApoA1/ApoB ratio
      (rs4131229); LDL-C, ApoB, and ApoA1/ApoB ratio (rs3806471); HDL-C, ApoA1, and
      ApoA1/ApoB ratio (rs4148211) in Han females were different between the genotypes
      (P<0.05-0.001). The levels of LDL-C in Mulao females were also different between
      GG and GC/CC genotypes of rs6720173 (P<0.05). The correlation between serum lipid
      parameters and genotypes of four SNPs was observed in Han, especially in Han
      males. Serum lipid parameters were also correlated with several environmental
      factors. CONCLUSIONS: The associations of four ABCG5/G8 SNPs and serum lipid
      levels are different between the Mulao and Han populations, or between males and
      females, suggesting that there may be a racial/ethnic- and/or sex-specific
      association between ABCG5/G8 SNPs and some serum lipid parameters.

PMID- 22655092
TI  - Musical ratios in sounds from the human cochlea.
AB  - The physiological roots of music perception are a matter of long-lasting debate.
      Recently light on this problem has been shed by the study of otoacoustic
      emissions (OAEs), which are weak sounds generated by the inner ear following
      acoustic stimulation and, sometimes, even spontaneously. In the present study, a
      high-resolution time-frequency method called matching pursuit was applied to the
      OAEs recorded from the ears of 45 normal volunteers so that the component
      frequencies, amplitudes, latencies, and time-spans could be accurately
      determined. The method allowed us to find that, for each ear, the OAEs consisted
      of characteristic frequency patterns that we call resonant modes. Here we
      demonstrate that, on average, the frequency ratios of the resonant modes from all
      the cochleas studied possessed small integer ratios. The ratios are the same as
      those found by Pythagoras as being most musically pleasant and which form the
      basis of the Just tuning system. The statistical significance of the results was
      verified against a random distribution of ratios. As an explanatory model, there
      are attractive features in a recent theory that represents the cochlea as a
      surface acoustic wave resonator; in this situation the spacing between the rows
      of hearing receptors can create resonant cavities of defined lengths. By
      adjusting the geometry and the lengths of the resonant cavities, it is possible
      to generate the preferred frequency ratios we have found here. We conclude that
      musical perception might be related to specific geometrical and physiological
      properties of the cochlea.

PMID- 22655093
TI  - Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by
      ifenprodil: the role of sigma-1 and IP3 receptors.
AB  - In addition to both the alpha1 adrenergic receptor and N-methyl-D-aspartate
      (NMDA) receptor antagonists, ifenprodil binds to the sigma receptor subtypes 1
      and 2. In this study, we examined the effects of ifenprodil on nerve growth
      factor (NGF)-induced neurite outgrowth in PC12 cells. Ifenprodil significantly
      potentiated NGF-induced neurite outgrowth, in a concentration-dependent manner.
      In contrast, the alpha1 adrenergic receptor antagonist, prazosin and the NMDA
      receptor NR2B antagonist, Ro 25-6981 did not alter NGF-induced neurite outgrowth.
      Potentiation of NGF-induced neurite outgrowth mediated by ifenprodil was
      significantly antagonized by co-administration of the selective sigma-1 receptor
      antagonist, NE-100, but not the sigma-2 receptor antagonist, SM-21. Similarly,
      ifenprodil enhanced NGF-induced neurite outgrowth was again significantly reduced
      by the inositol 1,4,5-triphosphate (IP(3)) receptor antagonists, xestospongin C
      and 2-aminoethoxydiphenyl borate (2-APB) treatment. Furthermore, BAPTA-AM, a
      chelator of intracellular Ca(2+), blocked the effects of ifenprodil on NGF
      induced neurite outgrowth, indicating the role of intracellular Ca(2+) in the
      neurite outgrowth. These findings suggest that activation at sigma-1 receptors
      and subsequent interaction with IP(3) receptors may mediate the pharmacological
      effects of ifenprodil on neurite outgrowth.

PMID- 22655094
TI  - The ter mutation in the rat Dnd1 gene initiates gonadal teratomas and infertility
      in both genders.
AB  - A spontaneous mutation leading to the formation of congenital ovarian and
      testicular tumors was detected in the WKY/Ztm rat strain. The histological
      evaluation revealed derivatives from all three germ layers, thereby identifying
      these tumors as teratomas. Teratocarcinogenesis was accompanied by infertility
      and the underlying mutation was termed ter. Linkage analysis of 58 (WKY-ter*SPRD
      Cu3) F2 rats associated the ter mutation with RNO18 (LOD = 3.25). Sequencing of
      candidate genes detected a point mutation in exon 4 of the dead-end homolog 1
      gene (Dnd1), which introduces a premature stop codon assumed to cause a
      truncation of the Dnd1 protein. Genotyping of the recessive ter mutation revealed
      a complete penetrance of teratocarcinogenesis and infertility in homozygous ter
      rats of both genders. Morphologically non-tumorous testes of homozygous ter males
      were reduced in both size and weight. This testicular malformation was linked to
      a lack of spermatogenesis using immunohistochemical and histological staining.
      Our WKY-Dnd1(ter)/Ztm rat is a novel animal model to investigate gonadal
      teratocarcinogenesis and the molecular mechanisms involved in germ cell
      development of both genders.

PMID- 22655095
TI  - The association between individual SNPs or haplotypes of matrix metalloproteinase
      1 and gastric cancer susceptibility, progression and prognosis.
AB  - BACKGROUND: The single nucleotide polymorphisms (SNPs) in matrix
      metalloproteinase 1(MMP-1) play important roles in some cancers. This study
      examined the associations between individual SNPs or haplotypes in MMP-1 and
      susceptibility, clinicopathological parameters and prognosis of gastric cancer in
      a large sample of the Han population in northern China. METHODS: In this case
      controlled study, there were 404 patients with gastric cancer and 404 healthy
      controls. Seven SNPs were genotyped using the MALDI-TOF MS system. Then, SPSS
      software, Haploview 4.2 software, Haplo.states software and THEsias software were
      used to estimate the association between individual SNPs or haplotypes of MMP-1
      and gastric cancer susceptibility, progression and prognosis. RESULTS: Among
      seven SNPs, there were no individual SNPs correlated to gastric cancer risk.
      Moreover, only the rs470206 genotype had a correlation with histologic grades,
      and the patients with GA/AA had well cell differentiation compared to the
      patients with genotype GG (OR=0.573; 95%CI: 0.353-0.929; P=0.023). Then, we
      constructed a four-marker haplotype block that contained 4 common haplotypes:
      TCCG, GCCG, TTCG and TTTA. However, all four common haplotypes had no correlation
      with gastric cancer risk and we did not find any relationship between these
      haplotypes and clinicopathological parameters in gastric cancer. Furthermore,
      neither individual SNPs nor haplotypes had an association with the survival of
      patients with gastric cancer. CONCLUSIONS: This study evaluated polymorphisms of
      the MMP-1 gene in gastric cancer with a MALDI-TOF MS method in a large northern
      Chinese case-controlled cohort. Our results indicated that these seven SNPs of
      MMP-1 might not be useful as significant markers to predict gastric cancer
      susceptibility, progression or prognosis, at least in the Han population in
      northern China.

PMID- 22655096
TI  - [Acute abdomen in a torsion of an ectopic spleen: report of a case].

PMID- 22655097
TI  - Ectopic molar pregnancy: a case report.
AB  - The incidence of hydatidiform moles is 1 per 1,000 pregnancies. Ectopic pregnancy
      occurs in 20 per 1,000 pregnancies. Thus, the incidence of the ectopic molar
      gestation is very rare. We report a case of tubal molar pregnancy diagnosed at
      the systematic histology exam of an ectopic pregnancy. We report the case of 32
      years old nulliparus women who presented a vaginal bleeding, lower abdominal pain
      and 6 weeks amenorrhea corresponding to the last menstrual period. At the
      clinical examination, the arterial pressure was 100/60 mmHG. The gynecological
      examination was difficult because of lower abdominal pain. Serum gonadotropin
      activity was 3454 ui/l. Pelvic ultrasound revealed an irregular echogenic mass in
      the left adnexa. Diagnostic laparoscopy revealed a left-sided unruptured
      ampullary ectopic pregnancy. A left laparoscopic salpingectomy was performed. The
      systematic histologic test identified an ectopic partial molar pregnancy, which
      was confirmed by DNA ploidy image analysis. The patient was followed with weekly
      quantitative B-hCG titers until three successive B-hCG levels were negative. It
      is pertinent that clinicians take routine histological examination of tubal
      specimens in ectopic pregnancy very seriously in order to diagnose cases of
      ectopic molar gestations early and mount appropriate post treatment surveillance.

PMID- 22655098
TI  - [Tarsal osteoarthritis tuberculosis: report of a case].

PMID- 22655099
TI  - [Sexual and reproductive health of adolescent girls in Bobo Dioulasso, Burkina
      Faso: the role of parent-adolescent communication for risk reduction].

PMID- 22655100
TI  - Hospital-based mortality in Federal Capital Territory hospitals--Nigeria, 2005
      2008.
AB  - BACKGROUND: Cause-specific mortality data are important to monitor trends in
      mortality over time. Medical records provide reliable documentation of the causes
      of deaths occurring in hospitals. This study describes all causes of mortality
      reported at hospitals in the Federal Capital Territory (FCT) of Nigeria. METHODS:
      Deaths reported in 15 secondary and tertiary FCT hospitals occurring from January
      1, 2005 and December 31, 2008 were identified by a retrospective review of
      hospital records conducted by the Nigeria Field Epidemiology and Laboratory
      Program (NFELTP). Data extracted from the records included sociodemographics,
      geographic area of residence and underlying cause-of-death information. RESULTS:
      A total of 4,623 deaths occurred in the hospitals. Overall, the top five causes
      of death reported were: HIV 951 (21%), road traffic accidents 422 (9%), malaria
      264 (6%), septicemia 206 (5%), and hypertension 194 (4%). The median age at death
      was 30 years (range: 0-100); 888 (20%) of deaths were among those less than one
      year of age. Among children < 1 year, low birth weight and infections were
      responsible for the highest proportion 131 (15%) of reported mortality.
      CONCLUSION: Many of the leading causes of mortality identified in this study are
      preventable. Infant mortality is a large public health problem in FCT hospitals.
      Although these findings are not representative of all FCT deaths, they may be
      used to quantify mortality in that occurs in FCT hospitals. These data combined
      with other mortality surveillance data can provide evidence to inform policy on
      public health strategies and interventions for the FCT.

PMID- 22655101
TI  - Comparison of different blood pressure indices for the prediction of prevalent
      diabetic nephropathy in a sub-Saharan African population with type 2 diabetes.
AB  - BACKGROUND: The association between blood pressure (BP) and diabetic kidney
      diseases in Africans has been less well investigated. We assessed and compared
      the strength of the association and discriminatory capability of systolic (SBP),
      diastolic (DBP) BP, pulse pressure (PP) and mean arterial blood pressure (MAP)
      for nephropathy risk in sub-Saharan Africans with type 2 diabetes. METHODS:
      Participants were 420 consecutive individuals (49% men) with type 2 diabetes
      receiving chronic care in two main referral centres in the two major cities of
      Cameroon. Logistic regression models were used to compute the odd ratio (OR) and
      95% confidence interval (95% CI) for a standard deviation (SD) higher level of
      SBP (25 mmHg), DBP (13), PP (18) and MAP (16) with nephropathy risk.
      Discrimination was assessed and compared with c-statistics and relative
      integrated discrimination improvement (RIDI, %). RESULTS: The adjusted OR (95%
      CI) for nephropathy with each SD higher BP variable were: 1.45 (1.15-1.84) for
      SBP, 1.33 (1.06-1.66) for DBP, 1.35 (1.06-1.71) for PP and 1.42 (1.13-1.78) for
      MAP. C-statistic comparison showed no difference in discrimination of models with
      each of the BP variables (p-values >= 0.69 for c-statistics comparison). However,
      RIDI statistic always showed and enhancement in models discrimination when other
      BP variables were replaced with SBP, although such an enhancement was marginal
      for MAP. Using BP combination modestly improved models? discrimination.
      CONCLUSION: SBP was the best predictor of prevalent nephropathy in this
      population, while DBP was the less effective. This may have implication for
      kidney disease risk stratification and protection.

PMID- 22655102
TI  - Malignant melanoma of the lung: a case report.
AB  - Primary melanoma of the lung is an extremely rare pathological entity and
      sparsely reported in the literature. A 68-year-old man was admitted with 3 months
      history of cough, sputum production, dyspnea, hemoptysis and chest pain. The
      chest radiography demonstrated bilateral mass lesion and thoracal computerized
      (CT) showed a bilateral tissu mass with left parietal invasion. Bronchoscopy
      revealed a large polypoidal tumor arising from the left lower lobe bronchus,
      histology at bronchial biopsy revealed a malignant melanoma. Surgical biopsy of
      the left parietal mass was confirmed by invasive malignant melanoma. Primary
      melanoma of the lung represents a rare pathological entity; careful
      interpretation of histopathological information in correlation with all other
      findings from clinical studies can establish a diagnosis.

PMID- 22655103
TI  - Perception and utilization of cervical cancer screening services among female
      nurses in University College Hospital, Ibadan, Nigeria.
AB  - BACKGROUND: Cervical Cancer (CC) is the second most common cancer among women
      with early detection and prompt treatment as best management options. Female
      nurses have crucial roles to play in promoting the utilization of Cervical Cancer
      Screening Services (CCSS), yet little information exist regarding their
      perception and utilization of these services. The CCSS related knowledge,
      perception and utilization among female nurses at the University College
      Hospital, (UCH) Ibadan, Nigeria were therefore determined. METHODS: A survey of
      503 consenting nurses was done using a pretested self-administered questionnaire
      which included a 40-point knowledge scale and questions on perception of CC. Data
      were analyzed using descriptive statistics, Chi-square test, ANOVA and logistic
      regression. RESULTS: Respondents' mean age was 38.0 +/- 8.6 years, mean year of
      experience was 12.5 +/- 8.9 years and overall mean knowledge score was 22.8+/
      4.1. Mean knowledge scores by cadre were Assistant Directors (26.7 +/- 1.5),
      Chief Nursing Officers (23.4 +/- 2.3) and Staff Nurses (21.7 +/- 5.3) (p<0.05).
      Eighty-eight percent correctly perceived CC to be preventable and 82.0% believed
      that screening should be carried out as soon as sexual intercourse starts
      irrespective of age. Only 32.6% had ever used CCSS facility and main reasons for
      non-use included lack of time (50.8%), fear of result (13.9%) and not being
      sexually active (6.3%). Staff Nurses were four times less likely to utilize
      cervical screening services than the Assistant Directors of Nursing (OR 0.23, CI
      0.117-0.442). CONCLUSION: Utilization of cervical cancer screening services among
      the female nurses was poor. Strategies that encourage utilization are hereby
      advocated.

PMID- 22655104
TI  - Breast cancer knowledge and awareness among university students in Angola.
AB  - BACKGROUND: The high breast cancer mortality rate in Sub-Saharan Africa has been
      attributed to a lack of public awareness of the disease which often leads to late
      diagnosis of the disease. Little is known about the level of knowledge and
      awareness of breast cancer in Angola. Previous studies have shown that breast
      cancer awareness is higher among well-educated people. The goal of this study was
      to assess breast cancer knowledge and awareness among university students in
      Angola. METHODS: We conducted a cross-sectional survey of university students
      using a self-administered questionnaire to investigate participants' awareness
      and knowledge of breast cancer. A total of 595 university students in medical and
      non-medical programs successfully completed the survey. RESULTS: Our results
      showed insufficient knowledge of breast cancer among university students in
      Angola irrespective of whether they were in medical or non-medical programs. The
      majority of the participants were not aware of some of the early signs of breast
      cancer such as change in color or shape of the nipple, even though they
      appreciated the need for monthly breast self-examination. Overall most of the
      participants indicated the need for increased breast cancer awareness among
      university students. CONCLUSION: The study points to the insufficient knowledge
      of university students in Angola about breast cancer. We expect that our results
      may provide useful data that may be used by the department of health in Angola
      and other African countries to formulate health education programs aimed at
      increasing awareness and promote screening and early detection of breast cancer
      in the continent.

PMID- 22655105
TI  - A United Nation high level meeting on chronic non-communicable diseases: utility
      for Africa?

PMID- 22655106
TI  - Atropa belladonna intoxication: a case report.
AB  - Atropa belladonna is a poisonous plant also called deadly nightshade. Its roots,
      leaves and fruits contain alkaloids: atropine, hyocyamine and scopolamine. The
      risk of poisoning in children is important because of possible confusion with
      other berries. Atropa belladonna acute intoxication is a severe condition, it's
      should be considered in the presence of anti-cholinergic toxidrome, the
      differential diagnosis include other plants or psychoactive drugs containing
      atropine. The treatment is mainly symptomatic including gastrointestinal
      decontamination with activated charcoal. In severe cases, physostigmine can be
      used as an antidote. We report the case of 11 year old girl with Atropa
      belladonna poisoning which was administrated in a therapeutic purpose as a remedy
      to jaundice. The child presented essentially a central anti-cholinergic syndrome.
      She was admitted in the intensive care unit, the progression was favorable with
      symptomatic treatment.

PMID- 22655107
TI  - Epidemiology of rotavirus diarrhea in children under 5 years in Northern
      Cameroon.
AB  - BACKGROUND: Rotavirus still remains the major cause of diarrhea in children below
      5 years. No data on rotavirus epidemiology is available in the Northern regions
      of Cameroon. We aimed to determine the prevalence of group A rotavirus (RVA) in
      children below 5 years with diarrhea in two regions of Northern Cameroon (North
      West and Far North Regions) so as to improve our knowledge on the burden of
      rotavirus disease for imminent introduction of a rotavirus vaccine. METHODS:
      Stool samples were collected during 2010 and 2011 from 390 children below 5 years
      presenting with diarrhea in four hospitals in Northern Cameroon and were screened
      for rotavirus group A by reverse transcription-polymerase chain reaction.
      RESULTS: This study revealed that 42.8% of the children below 5 years had group A
      rotavirus infection, 46.5% in the Far North region while the North West had a
      prevalence of 33.9%. Of the 252 hospitalized and the 138 outpatient children,
      124(49.2%) and 43(31.2%) (P=0.00085), respectively, were positive for group A
      rotavirus. Children below 24 months were most affected (44.7%), while the age
      group 49-60 months had the lowest prevalence (25%). The RVA prevalence was 44.6%
      in the urban and 28.9% in the rural settings of our study. It was observed that
      the proportion of children with diarrhea who had rotavirus accompanied with fever
      and vomiting in the outpatient group and inpatient group were 13.0% and 28.6%
      respectively, P=0.03. CONCLUSION: This study showed high incidence of rotavirus
      infection especially among hospitalized children in Northern Cameroon, suggesting
      that rotavirus is a major cause of childhood morbidity and mortality in this
      area.

PMID- 22655108
TI  - [Amniotic fluid embolism: report of two cases].

PMID- 22655109
TI  - Snoring and obstructive sleep apnoea syndrome among hypertensive Nigerians:
      prevalence and clinical correlates.
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) syndrome is a common disorder in the
      community. Association between hypertension and sleep apnoea and /or snoring has
      been described. The Berlin questionnaire is a validated instrument that is used
      to identify individuals who are at risk for OSA. The study aim to describe the
      prevalence of snoring and OSA among hypertensive subjects in South Western,
      Nigeria. METHODS: This was a descriptive study conducted at the Cardiology clinic
      of Ladoke Akintola University of Technology LAUTECH Teaching Hospital, Osogbo,
      South West Nigeria. One hundred consecutive hypertensive patients were recruited
      from the clinic. The Berlin questionnaire and the Epworth sleepiness scale (ESS)
      were used to determine excessive daytime sleepiness and the risk of having OSA.
      Statistical analysis was done using SPSS 16.0. Data were summarized as means +/-
      S.D and percentages. RESULTS: The study participants consisted of 40 males
      (40.0%). The demographic data were similar between both genders except that
      females had higher mean body mass index than males. The prevalence of snoring was
      50.0%. 52% were categorized as being at high risk of having OSA. Snorers were
      more likely to be older, males and to have a higher fasting blood sugar than non
      snorers. 96% of snorers reported excessive daytime somnolence as predicted by the
      ESS score compared to 4% of non snorers. Prevalence of snoring was also higher
      among overweight and obese hypertensive subjects than normal body mass index
      hypertensive subjects. CONCLUSION: Snoring is common among hypertensive subjects
      in South Western Nigeria. Clinically suspected OSA was similarly high in
      prevalence among them. Early identification and management may reduce the
      cardiovascular risk of hypertensive subjects.

PMID- 22655110
TI  - [Cavernous hemangioma of the rib: a rare tumor of the chest wall].

PMID- 22655111
TI  - [Screening for cardiovascular disease among students at the University of Douala
      and influence of sport and physical activity].

PMID- 22655112
TI  - Assessment of knowledge on neonatal resuscitation amongst health care providers
      in Kenya.
AB  - INTRODUCTION: Competence in neonatal resuscitation, which represents the most
      urgent pediatric clinical situation, is critical in delivery rooms to ensure
      safety and health of newly born infants. The challenges experienced by health
      care providers during this procedure are unique due to different causes of cardio
      respiratory arrest. This study aimed at assessing the knowledge of health
      providers on neonatal resuscitation. METHODS: Data were gathered among 192 health
      providers drawn from all counties of Kenya. The clinicians were asked to complete
      questionnaires which were in two parts as; demographic information and assessment
      of their knowledge by different scenarios which were formatted in the multiple
      choice questions. Data were analyzed using SPSS version 15.0 for windows. The
      results are presented using tables. RESULTS: All the participants were aged 23
      years and above with at least a certificate training. Most medical providers had
      heard of neonatal resuscitation (85.4%) with only 23 receiving formal training.
      The average duration of neonatal training was 3 hours with 50% having missed out
      on practical exposure. When asked on steps of resuscitation, only 68 (35.4%) of
      the participants scored above 85%. More than 70% of them considered their
      knowledge about neonatal resuscitation inadequate and blamed it on inadequate
      medical training programs. CONCLUSION: Health providers, as the key personnel in
      the management of neonatal resuscitation, in this survey seem to have inadequate
      training and knowledge on this subject. Increasing the duration and quality of
      formal training should be considered during the pre-service medical education to
      ensure acceptable neonatal outcome.

PMID- 22655113
TI  - Longitudinal fMRI analysis: A review of methods.
AB  - Functional magnetic resonance imaging (fMRI) investigations of a longitudinal
      nature, where participants are scanned repeatedly over time and imaging data are
      obtained at more than one time-point, are essential to understanding functional
      changes and development in healthy and pathological brains. The main objective of
      this paper is to provide a brief summary of common longitudinal analysis
      approaches, develop an overview of fMRI by introducing how such data manifest,
      and explore the statistical challenges that arise at the intersection of these
      two techniques.

PMID- 22655116
TI  - Avulsion of the auricle in an anticoagulated patient: is leeching
      contraindicated? A review and a case.
AB  - Amputation of the auricle is a periodic occurrence leading to disfigurement if
      not treated properly. Venous stasis is a common complication in reattachments and
      requires decongestant and anticoagulant treatment. Today, leech therapy is the
      treatment of choice. Common problems are that it is not available everywhere and
      that it is usually contraindicated in anticoagulated patients. The peculiarities
      of leech therapy and the various aspects of surgical management are reviewed. A
      case of a partial amputation of the auricle in a patient under concomitant
      anticoagulation therapy with warfarin is presented. The amputated part was
      reattached in another hospital without microvascular anastomosis. The patient
      presented to our department with early signs of venous congestion. Leech therapy
      was started 35 hours after trauma, and the patient continued his anticoagulation
      therapy. With this treatment, 90% of the amputated part was rescued. The
      anticoagulation therapy of the patient may have played an important role in the
      first hours after reattachment, preventing capillary thrombosis and in
      consequence facilitating the minimal oxygenation necessary. The claim that
      anticoagulation therapy is a contraindication to leeching should be questioned in
      cases of reattachments in well-controllable locations without arterial
      anastomosis.

PMID- 22655115
TI  - A combination of lipoic acid plus coenzyme Q10 induces PGC1alpha, a master switch
      of energy metabolism, improves stress response, and increases cellular
      glutathione levels in cultured C2C12 skeletal muscle cells.
AB  - Skeletal muscle function largely depend on intact energy metabolism, stress
      response, and antioxidant defense mechanisms. In this study, we tested the effect
      of a combined supplementation of alpha-lipoic acid (LA) plus coenzyme Q10 (Q10)
      on PPARgamma-coactivator alpha (PGC1alpha) activity, expression of glutathione
      related phase II enzymes and glutathione (GSH) levels in cultured C2C12 myotubes.
      Supplementation of myotubes with 250 MUmol/L LA plus 100 MUmol/L Q10
      significantly increased nuclear levels of PGC1alpha, a master switch of energy
      metabolism and mitochondrial biogenesis. The increase of nuclear PGC1alpha was
      accompanied by an increase in PPARgamma transactivation, a downstream target of
      PGC1alpha, and an increase in mitochondrial transcription factor A mRNA centrally
      involved in mitochondrial replication and transcription. Furthermore,
      supplementation of myotubes with LA plus Q10 resulted in an increase of genes
      encoding proteins involved in stress response, GSH synthesis, and its recycling.
      In LA-plus-Q10-treated myotubes a significant 4-fold increase in GSH was evident.
      This increase in GSH was accompanied by increased nuclear Nrf2 protein levels,
      partly regulating gammaGCS and GST gene expression. Present data suggest that the
      combined supplementation of skeletal muscle cells with LA plus Q10 may improve
      energy homeostasis, stress response, and antioxidant defense mechanisms.

PMID- 22655114
TI  - The neglected significance of "antioxidative stress".
AB  - Oxidative stress arises when there is a marked imbalance between the production
      and removal of reactive oxygen species (ROS) in favor of the prooxidant balance,
      leading to potential oxidative damage. ROSs were considered traditionally to be
      only a toxic byproduct of aerobic metabolism. However, recently, it has become
      apparent that ROS might control many different physiological processes such as
      induction of stress response, pathogen defense, and systemic signaling. Thus, the
      imbalance of the increased antioxidant potential, the so-called antioxidative
      stress, should be as dangerous as well. Here, we synthesize increasing evidence
      on "antioxidative stress-induced" beneficial versus harmful roles on health,
      disease, and aging processes. Oxidative stress is not necessarily an un-wanted
      situation, since its consequences may be beneficial for many physiological
      reactions in cells. On the other hand, there are potentially harmful effects of
      "antioxidative stress," especially in the cases of overconsumption of synthetic
      antioxidants. Antioxidants can neutralize ROS and decrease oxidative stress;
      however, this is not always beneficial in regard to disease formation or
      progression (of, e.g., cancer) or for delaying aging.

PMID- 22655117
TI  - A review of mandibular angle fractures.
AB  - AFTER STUDYING THIS ARTICLE, THE READER WILL BE ABLE TO: (1) review the incidence
      and etiology of mandibular angle fractures; (2) gain an understanding of patient
      evaluation and general management principles; and (3) discuss indications and
      available techniques for management of mandibular angle fractures. Angle
      fractures represent the highest percentage of mandibular fractures. Two of the
      most common causes of mandibular angle fractures are motor vehicle accidents and
      assaults or altercations. With any patient who has sustained facial trauma, a
      thorough history and comprehensive physical examination centering on the head and
      neck region as well as proper radiological assessment are essential. These
      elements are fundamental in establishing a diagnosis and developing an
      appropriate treatment plan for any mandibular fracture.

PMID- 22655118
TI  - Pediatric craniofacial trauma: challenging pediatric cases-craniofacial trauma.
AB  - The pediatric population, as well as the adult population, is subject to similar
      injuries and traumatic events involving the craniofacial skeleton. Although less
      frequent than adult injuries, the craniofacial injuries sustained by children are
      considered separately in textbooks and the literature because of the special
      unique problems associated with their treatment and the effects they might have
      on growth and development that can arise as a result of their management. Some of
      the more challenging cases that I have seen involve the very young with cranial
      bone fractures and cranial base fractures and those that involve the nasal and/or
      orbital-ethmoidal areas in young children and their secondary reconstruction.
      Some of these types of cases are not always clearly and thoroughly addressed in
      textbooks or articles because of their infrequent occurrence. Often, surgeons
      differ in approaches to treatment because of certain anatomic or physiological
      factors specifically related to childhood, facial growth, and the timing of
      treatment. Some of the cranial and facial developmental malformations seen in
      older children or adults can be attributed to trauma sustained in early
      childhood. This is because trauma may have a deleterious effect on the growth and
      development of facial structures in the postnatal life similar to that seen
      resulting from a genetic mutation.

PMID- 22655119
TI  - Management of jaw injuries in the american civil war: the diuturnity of bean in
      the South, gunning in the north.
AB  - James Baxter Bean published a series of articles in the Southern Dental Examiner
      in 1862 describing his work with "plaster and its manipulations." This early
      experience included a new way of managing jaw fractures, with customized splints
      uniquely based on pretraumatic occlusion. Bean's oral splints and their method of
      construction, using an articulator, became the standard of care in the Atlanta
      region during the American Civil War and, by 1864, throughout The Confederacy. In
      short course, Bean's approach also swept The Union, following in large part the
      efforts of a colleague in the North, T.B. Gunning. Thus, what began in the early
      1860s in a dental laboratory in the southeast swept the continental United States
      and revolutionized management of jaw-fractures during, and immediately after, the
      American Civil War.

PMID- 22655120
TI  - A new device for alveolar bone transportation.
AB  - We present a retrospective review of a new technique for the transportation of
      alveolar bone using a Hyrax device modified by the principal author (O.A.V.).
      There were seven patients (five males and two females), including five patients
      with cleft palate and lip diagnosis, one patient with a high-speed gunshot wound,
      and one patient with facial trauma sequel due to mandibular fracture. They were
      all treated with an alveolar bone transportation technique (ABT) through the use
      of the modified Hyrax device (VEGAX). Before surgery, distraction osteogenesis of
      the bifocal type was performed on four patients, and the trifocal type was
      performed on the other three patients. However, in one case, direct dental
      anchorage was not used, only orthodontic appliances. In all the cases, new bone
      formation and gingival tissue around the defect were obtained, posterior to the
      alveolar distraction process; no complications were observed in any patient. In
      one case, two teeth involved in the disk of the ABT were extracted, due to a
      previous condition of periodontal disease. The alveolar bone transport with the
      VEGAX device is an accessible technique for almost every patient with alveolar
      defects due to diverse causes. In all the presented cases, predictability and
      success were demonstrated.

PMID- 22655121
TI  - Intraoral approach for treatment of displaced condylar fractures: case report.
AB  - Dislocated subcondylar fractures often require open reduction and internal
      fixation. This treatment modality results in better anatomy, early function, and
      facilitated physical therapy. Ideal stable fixation is obtained by use of two
      miniplates to control the tension zone in the sigmoid notch area and stabilize
      the posterior border region or, if there is not enough space, one stronger plate.
      That is most frequently achieved through extraoral approaches. Recently new
      instruments have facilitated the use of an intraoral approach, which is used
      usually with the aid of an endoscope. However, it is possible to perform the
      procedure without the endoscope if proper instruments and clinical mirrors for
      checking the posterior border reduction and fixation are used. A case of
      reduction and fixation of a medially dislocated condylar fracture is presented
      and discussed.

PMID- 22655122
TI  - Atypical case of congenital maxillomandibular fusion with duplication of the
      craniofacial midline.
AB  - We report the first case of syngnathia with hypophyseal duplication and describe
      the central nervous system (CNS) and craniofacial anomalies associated with
      hypophyseal duplication in the reported autopsy case. We studied clinical
      reports, scanner images, and autopsy results of a 2-months-old female baby. The
      propositus had frontonasal dysmorphism, retrognathia, and bifid tongue. She also
      presented maxillomandibular bony fusion (syngnathia) and an intraoral hairy
      polyp. In the cranium, the sella turcica was broadened, with two complete
      hypophyses and two infundibulums. The CNS had both olfactory bulbs and corpus
      callosum agenesis. There are 27 previous cases of maxillomandibular fusion and
      seven previous autopsy cases of hypophyseal duplication associated with other
      frontonasal malformations. As far as the authors know, this is the first case
      reported in the literature that associates syngnathia with duplication of the
      craniofacial midline including hypophyseal duplication.

PMID- 22655123
TI  - PARP Inhibitors for the Treatment and Prevention of Breast Cancer.
AB  - Poly (ADP-ribose) polymerase (PARP) inhibitors, a novel class of drugs that
      target tumors with DNA repair defects, have received tremendous enthusiasm. Early
      preclinical studies identified BRCA1 and BRCA2 tumors to be highly sensitive to
      PARP inhibitors as a result of homologous recombination defect. Based on this
      premise, PARP inhibitors have been tested in early phase clinical trials as a
      single agent in BRCA1 or BRCA2 mutation carriers and in combination with
      chemotherapy in triple-negative breast cancer patients. For high-risk
      populations, use of PARP inhibition as a prevention agent has been postulated,
      but no robust preclinical or clinical studies exist yet. We review the
      preclinical and clinical studies in treatment of breast cancer and rationale for
      use of PARP inhibitors as a prevention agent for high-risk populations. Of
      significance, PARP inhibitors vary significantly in mechanism of action, dosing
      intervals, and toxicities, which are highlighted in this review.

PMID- 22655124
TI  - Pancreatic adenocarcinoma: Outstanding problems.
AB  - Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related
      death and is one of the most aggressive malignant tumors with an overall 5-year
      survival rate of less than 4%. Surgical resection remains the only potentially
      curative treatment but is only possible for 15%-20% of patients with pancreatic
      adenocarcinoma. About 40% of patients have locally advanced nonresectable
      disease. In the past, determination of pancreatic cancer resectability was made
      at surgical exploration. The development of modern imaging techniques has allowed
      preoperative staging of patients. Institutions disagree about the criteria used
      to classify patients. Vascular invasion in pancreatic cancers plays a very
      important role in determining treatment and prognosis. There is no evidence-based
      consensus on the optimal preoperative imaging assessment of patients with
      suspected pancreatic cancer and a unified definition of borderline resectable
      pancreatic cancer is also lacking. Thus, there is much room for improvement in
      all aspects of treatment for pancreatic cancer. Multi-detector computed
      tomography has been widely accepted as the imaging technique of choice for
      diagnosing and staging pancreatic cancer. With improved surgical techniques and
      advanced perioperative management, vascular resection and reconstruction are
      performed more frequently; patients thought once to be unresectable are
      undergoing radical surgery. However, when attempting heroic surgery, a realistic
      approach concerning the patient's age and health status, probability of recovery
      after surgery, perioperative morbidity and mortality and life quality after tumor
      resection is necessary.

PMID- 22655125
TI  - Arguments for an individualized closure of the pancreatic remnant after distal
      pancreatic resection.
AB  - AIM: To analyze risk factors for postoperative pancreatic fistula (POPF) rate
      after distal pancreatic resection (DPR). METHODS: We performed a retrospective
      analysis of 126 DPRs during 16 years. The primary endpoint was clinically
      relevant pancreatic fistula. RESULTS: Over the years, there was an increasing
      rate of operations in patients with a high-risk pancreas and a significant change
      in operative techniques. POPF was the most prominent factor for perioperative
      morbidity. Significant risk factors for pancreatic fistula were high body mass
      index (BMI) [odds ratio (OR) = 1.2 (CI: 1.1-1.3), P = 0.001], high-risk
      pancreatic pathology [OR = 3.0 (CI: 1.3-7.0), P = 0.011] and direct closure of
      the pancreas by hand suture [OR = 2.9 (CI: 1.2-6.7), P = 0.014]. Of these, BMI
      and hand suture closure were independent risk factors in multivariate analysis.
      While hand suture closure was a risk factor in the low-risk pancreas subgroup,
      high BMI further increased the fistula rate for a high-risk pancreas. CONCLUSION:
      We propose a risk-adapted and indication-adapted choice of the closure method for
      the pancreatic remnant to reduce pancreatic fistula rate.

PMID- 22655126
TI  - Surgical management and outcomes of severe gastrointestinal injuries due to
      corrosive ingestion.
AB  - AIM: To report our experience in the surgical management of severe injuries of
      the gastrointestinal tract due to corrosive ingestion. METHODS: A retrospective
      review of patients who underwent emergency surgery for severe gastrointestinal
      injuries following corrosive ingestion between 1983 and 2010 was carried out.
      Data was extracted from a prospectively maintained esophageal disease database.
      Severe corrosive injuries were defined as full thickness necrosis with
      perforation of the esophagus or the stomach (with or without involvement of the
      adjacent viscera) with resultant mediastinitis or peritonitis. RESULTS: Between
      1983 and 2010, 209 patients with corrosive injury of the esophagus were managed.
      Of these, 13 (6.2%) patients underwent emergency surgery for severe corrosive
      injury. The median age of the patients was 22 years and the median interval
      between ingestion of the corrosive substance and surgery was 24 h. The surgical
      procedures done included esophagogastrectomy alone (n = 6), esophagogastrectomy
      with duodenectomy (n = 4), esophagogastrectomy with pancreaticoduodenectomy (n =
      1), esophagogastrectomy with splenectomy (n = 1) and distal gastrectomy with
      duodenectomy (n = 1). Two patients died in the postoperative period and one after
      discharge awaiting the second surgery. The factors significantly predictive of
      mortality following such an injury included renal failure at the time of initial
      presentation, presence of metabolic acidosis, delay of more than 24 h between
      corrosive ingestion and surgery, and corrosive induced adjacent organ injury
      (pancreatic) (P < 0.001, 0.02, 0.005 and 0.015 respectively). Ten patients
      underwent subsequent surgery for restoration of the alimentary tract continuity
      with a colonic pull-up (n = 8) and gastrojejunostomy (n = 1). In one patient, the
      attempted colon pull-up failed due to extensive scarring of the mesocolon. The
      median follow up (following restoration of continuity of the gastrointestinal
      tract) was 36.5 mo. One patient developed dysphagia due to a stricture at the
      anastomotic site, which was successfully managed by dilatation. Another patient
      developed severe aspiration, necessitating laryngeal inlet closure and permanent
      tracheostomy, and 3 patients complained of occasional regurgitation. CONCLUSION:
      Management of severe corrosive injury involves prompt resuscitation and urgent
      surgical debridement. Although the subsequent restoration of continuity may be
      complicated and may not always be possible, long term outcomes are acceptable in
      the majority.

PMID- 22655127
TI  - Posterior approach (Kraske procedure) for surgical treatment of presacral tumors.
AB  - Presacral tumors are rare, but can comprise a great variety of histological
      types. Congenital tumors are the most common. Once the diagnosis is established,
      surgical resection is essential because of the potential for malignancy or
      infection. Previous biopsy is not necessary or may be even harmful. To decide the
      best surgical approach (abdominal, sacral or combined) an individual and
      multidisciplinary analysis must be carried out. We report three cases of cystic
      presacral masses in which a posterior approach (Kraske procedure) enabled
      complete resection, the only way to decrease local recurrence. All patients had a
      satisfactory recovery. A brief overview of retrorectal tumors is presented,
      focusing on classification, clinical presentation, diagnosis and surgical
      management.

PMID- 22655128
TI  - Adult intussusception with cecal adenocarcinoma: Successful treatment by
      laparoscopy-assisted surgery following preoperative reduction.
AB  - We report a case of adult intussusception caused by cecal adenocarcinoma that was
      treated by laparoscopy-assisted ileocecal resection following reduction by
      contrast enema and preoperative colonoscopy. A 68-year-old male with cecal cancer
      was admitted to our hospital because of colicky abdominal pain after taking a
      laxative. His abdomen was distended, and a mass was palpable in the right upper
      quadrant, which appeared as a target- or sausage-shaped lesion by ultrasonograhpy
      and computed tomography. A contrast enema using water-soluble material showed a
      cup-shaped filling defect characterized by intussusception in the ascending
      colon. This round defect with a clear margin was pushed gradually back into the
      cecum by the enema pressure. Re-occurrence of the intussusception is easily
      released by colonoscopy. We performed laparoscopy-assisted ileocecal resection of
      a protruding tumor measuring 6.5 cm * 5.0 cm * 3.5 cm from the cecum, with D3
      lymph node dissection. Histological examination revealed a well-differentiated
      adenocarcinoma that had invaded the serosa without permeating the lymphatic or
      venous capillaries, as well as lymph node metastasis. The postoperative course
      was uneventful, and the patient has been well without evidence of disease
      recurrence for 5 years following the operation. Preliminary reduction of adult
      colonic intussusception before surgical resection is therefore an option in cases
      of an early and correct diagnosis of intussusception.

PMID- 22655129
TI  - A primer on the validity of assessment instruments.

PMID- 22655130
TI  - Deconstructing quality in education research.

PMID- 22655131
TI  - The hidden costs of failing to fail residents.

PMID- 22655132
TI  - An International Health Track Is Associated With Care for Underserved US
      Populations in Subsequent Clinical Practice.
AB  - BACKGROUND: Recent efforts to increase insurance coverage have revealed limits in
      primary care capacity, in part due to physician maldistribution. Of interest to
      policymakers and educators is the impact of nontraditional curricula, including
      global health education, on eventual physician location. We sought to measure the
      association between graduate medical education in global health and subsequent
      care of the underserved in the United States. METHODS: In 2005, we surveyed 137
      graduates of a family medicine program with one of the country's longest-running
      international health tracks (IHTs). We compared graduates of the IHT, those in
      the traditional residency track, and graduates prior to IHT implementation,
      assessing the anticipated and actual involvement in care of rural and other
      underserved populations, physician characteristics, and practice location and
      practice population. RESULTS: IHT participants were more likely to practice
      abroad and care for the underserved in the United States in the first 5 years
      following residency than non-IHT peers. Their current practices were more likely
      to be in underserved settings and they had higher percentages of uninsured and
      non-English-speaking patients. Comparisons between pre-IHT and post-IHT inception
      showed that in the first 5 years following residency, post-IHT graduates were
      more likely to care for the underserved and practice in rural areas and were
      likely to offer volunteer community health care services but were not more likely
      to practice abroad or to be in an academic practice. CONCLUSIONS: Presence of an
      IHT was associated with increased care of underserved populations. After the
      institution of an IHT track, this association was seen among IHT participants and
      nonparticipants and was not associated with increased long-term service abroad.

PMID- 22655133
TI  - A survey of resident opinions on peer evaluation in a large internal medicine
      residency program.
AB  - BACKGROUND: Starting in the 1960s, studies have suggested that peer evaluation
      could provide unique insights into the performance of residents in training.
      However, reports of resident resistance to peer evaluation because of
      confidentiality issues and the possible impact on their working relationships
      raised concerns about the acceptability and utility of peer evaluation in
      graduate medical education. The literature suggests that peers are able to
      reliably assess communication, interpersonal skills, and professionalism and
      provide input that may differ from faculty evaluations. This study assessed the
      attitudes of internal medicine residents 1 year after the implementation of a
      peer-evaluation system. METHODS: During the 2005-2006 academic year, we conducted
      an anonymous survey of the 168 residents in the Internal Medicine Residency
      Program at the Mayo Clinic, Rochester, Minnesota. Contingency table analysis was
      used to compare the response patterns of the groups. RESULTS: The response rate
      was 61% (103/168 residents) and it did not differ by year of training. Most
      residents (74/103; 72%) felt that peers could provide valuable feedback. Eighty
      percent of residents (82/103) felt the feedback was important for their
      professional development and 84% (86/102) agreed that peers observe behaviors not
      seen by attending faculty. CONCLUSIONS: The results of this study suggest that
      internal medicine residents provide unique assessment of their peers and provide
      feedback they consider important for their professional development. More
      importantly, the results support the role of peer evaluation in the assessment of
      the competencies of professionalism and interpersonal and communication skills.

PMID- 22655134
TI  - Observational study using the tools of lean six sigma to improve the efficiency
      of the resident rounding process.
AB  - BACKGROUND: Recent focus on resident work hours has challenged residency programs
      to modify their curricula to meet established duty hour restrictions and fulfill
      their mission to develop the next generation of clinicians. Simultaneously,
      health care systems strive to deliver efficient, high-quality care to patients
      and families. The primary goal of this observational study was to use a data
      driven approach to eliminate examples of waste and variation identified in
      resident rounding using Lean Six Sigma methodology. A secondary goal was to
      improve the efficiency of the rounding process, as measured by the reduction in
      nonvalue-added time. METHODS: We used the "DMAIC" methodology: define, measure,
      analyze, improve, and control. Pediatric and family medicine residents rotating
      on the pediatric hospitalist team participated in the observation phase.
      Residents, nurses, hospitalists, and parents of patients completed surveys to
      gauge their attitudes toward rounds. The Mann-Whitney test was used to test for
      differences in the median times measured during the preimprovement and
      postimprovement phases, and the Student t test was used for comparison of survey
      data. RESULTS AND DISCUSSION: Collaborative, family-centered rounding with
      elimination of the "prerounding" process, as well as standard work instructions
      and pacing the process to meet customer demand (takt time), were implemented.
      Nonvalue-added time per patient was reduced by 64% (P  =  .005). Survey data
      suggested that team members preferred the collaborative, family-centered approach
      to the traditional model of rounding. CONCLUSIONS: Lean Six Sigma provides tools,
      a philosophy, and a structured, data-driven approach to address a problem. In our
      case this facilitated an effort to adhere to duty hour restrictions while
      promoting education and quality care. Such approaches will become increasingly
      useful as health care delivery and education continue to transform.

PMID- 22655135
TI  - Behavioral evaluations of anesthesiology residents and overuse of the first
      person pronoun in personal statements.
AB  - BACKGROUND: The admissions process for residency encompasses numerous objective
      and subjective measurements by which an applicant is evaluated. The personal
      interview and clinical evaluations are widely considered the most reliable method
      to identify unwanted behavioral characteristics. However, the role of a personal
      statement is less clear. There are reports of residency programs attempting to
      identify selfish or egocentric behavioral traits by counting the frequency of the
      first-person pronoun "I" in personal statements. The purpose of this study is to
      define the relationship between anesthesiology resident evaluations and the
      frequency of the first-person pronoun within their personal statements. METHODS:
      Resident evaluations of 48 anesthesiology graduates were collected for 5
      competencies. The iScore was calculated by determining the frequency of "I" in
      relation to total word count. RESULTS: Correlation analysis between iScore and
      the 5 evaluation categories showed no significant relationship. CONCLUSION: When
      examining the relationship between resident evaluations and iScore, the lack of
      significant correlation makes it difficult to predict resident performance based
      on "I" counts. This may be because the personal statement is a thoughtfully
      developed document that undergoes extensive editing, which may suppress or
      minimize writing styles that suggest the presence of unwanted behavioral traits.
      Further examination of personal statements with a larger sample size and data
      from other institutions and specialties are needed.

PMID- 22655136
TI  - What residents know about health care reform and what we should teach them.
AB  - PURPOSE: We surveyed residents and fellows at the University of Louisville School
      of Medicine (N  =  600) to (1) explore their perceptions and knowledge of issues
      related to health care business and health care reforms, and (2) seek their input
      on what instructional content concerning health care business and health care
      reform they would like to receive and what instruction venue they would prefer.
      We will use the findings to make decisions about curriculum content and delivery.
      METHODS: All residents were invited to complete a 4-part, web-based survey that
      included questions on demographics, attitudes, and perceptions; a baseline
      knowledge quiz about health care costs; and 2 open-ended questions about what
      they wanted to learn and how they preferred to be taught. RESULTS: The survey
      response rate was 24%. Residents' agreement was stronger for statements relating
      to the role of physicians as "gatekeepers," patient-centered care, and the value
      of learning to work as a team than it was for statements about the benefits of
      government intervention in health care. International medical graduates, when
      compared with US medical graduates, had statistically significant differences in
      perceptions (P <= .004) on 3 questions related to government impact on health
      care. There was a slight decrease in overall knowledge about health care cost
      issues by residents in later postgraduate years. CONCLUSION: Residents are aware
      of gaps in their knowledge on business aspects of health care and health care
      reform. Their narrative responses identified coding and billing, legal issues,
      and comparative health systems as topics of interest, and the best venues for
      teaching included grand rounds and noon conferences. Residents indicated a
      preference for brief, highly focused, interactive sessions with knowledgeable
      guest speakers.

PMID- 22655137
TI  - Use of ecological momentary assessment to guide curricular change in graduate
      medical education.
AB  - PURPOSE: To assess whether a novel evaluation tool could guide curricular change
      in an internal medicine residency program. METHOD: The authors developed an 8
      item Ecological Momentary Assessment tool and collected daily evaluations from
      residents of the relative educational value of 3 differing ambulatory morning
      report formats (scale: 8  =  best, 0  =  worst). From the evaluations, they made
      a targeted curricular change and used the tool to assess its impact. RESULTS:
      Residents completed 1388 evaluation cards for 223 sessions over 32 months, with a
      response rate of 75.3%. At baseline, there was a decline in perceived educational
      value with advancing postgraduate (PGY) year for the overall mean score (PGY-1,
      7.4; PGY-2, 7.2; PGY-3, 7.0; P < .01) and for percentage reporting greater than 2
      new things learned (PGY-1, 77%; PGY-2, 66%; PGY-3, 50%; P < .001). The authors
      replaced the format of a lower scoring session with one of higher cognitive
      content to target upper-level residents. The new session's mean score improved
      (7.1 to 7.4; P  =  .03); the adjusted odds ratios before and after the change for
      percentage answering, "Yes, definitely" to "Area I need to improve" was 2.53 (95%
      confidence interval [CI], 1.45-4.42; P  =  .001) and to "Would recommend to
      others," it was 2.08 (95% CI, 1.12-3.89; P  =  .05). CONCLUSIONS: The Ecological
      Momentary Assessment tool successfully guided ambulatory morning report
      curricular changes and confirmed successful curricular impact. Ecological
      Momentary Assessment concepts of multiple, frequent, timely evaluations can be
      successfully applied in residency curriculum redesign.

PMID- 22655138
TI  - Pediatric Resident-as-Teacher Curricula: A National Survey of Existing Programs
      and Future Needs.
AB  - BACKGROUND: We conducted a national survey of US pediatric program directors to
      explore the current status, content, and teaching methods of Resident-as-Teacher
      (RAT) curricula. The purposes of the survey were to (1) determine the level and
      method of evaluation of such curricula, and (2) assess the need for a national
      curricular resource in this area. METHODS: A survey was sent to US pediatric
      program directors that asked questions regarding demographics, support, design,
      development, content, and evaluation of RAT curricula, as well as existing needs
      and desires for RAT curricular resources. RESULTS: Sixty-two percent of pediatric
      program directors completed our survey. Eighty-seven percent have a formal RAT
      curriculum, but more than 50% allocate 10 hours or less to it during residency.
      The primary teaching modalities are lectures and workshops. Content areas include
      feedback, in-patient teaching, communication skills, case-based teaching, role
      modeling, evaluation, leadership skills, 1-minute preceptors, teaching/learning
      styles, professionalism, and small-group teaching. Sixty-three percent of
      programs report evaluating their curricula, but only 27% perceive their program
      to be very/extremely effective. Nearly all respondents expressed interest in a
      national RAT curriculum, preferring web-based modules for dissemination.
      CONCLUSIONS: Despite an Accreditation Council for Graduate Medical Education
      requirement for a RAT curriculum, some pediatrics programs still lack one, and
      some consider their program only moderately effective. A wealth of curricular
      material exists across programs, which could be shared nationally. Establishing a
      national RAT curriculum would offer programs resources to meet educational
      mandates and the ability to tailor programs to best fit their own program needs.

PMID- 22655139
TI  - Conflict styles in a cohort of graduate medical education administrators,
      residents, and board-certified physicians.
AB  - OBJECTIVE: To assess conflict styles and construct validity of the Thomas-Kilmann
      Mode of Conflict Instrument (TKI) among medical education personnel. METHODS:
      From 2006 to 2009, 23 board-certified physicians (faculty), 46 residents, and 31
      graduate medical education (GME) administrators participated in 3 behavior
      surveys. We used self-reported data (as completed by participants on the
      questionnaire). The TKI defines 5 conflict styles: competing, collaborating,
      compromising, accommodating, and avoiding. The My Best Communication Style Survey
      assesses 4 styles of communication: bold, expressive, sympathetic, and technical.
      The Interpersonal Influence Inventory categorizes 4 behavior styles: openly
      aggressive, assertive, concealed aggressive, and passive behaviors. A P value of
      < .05 was significant. RESULTS: Avoiding was the conflict style most chosen,
      closely followed by compromising and accommodating, whereas collaborating was the
      least likely to be selected. Collaborating percentiles were highest in GME
      administrators and lowest in faculty. Competing percentiles decreased from
      faculty to GME administrators (r  =  -0.237, P  =  .017). Openly aggressive
      scores were highest in faculty and lowest in GME administrators (P  =  .028).
      Technical communication scores were highest in residents and lowest in GME
      administrators (P  =  .008). Technical communication scores were highest in
      African Americans (P  =  .000). Asian Americans were more likely to be high in
      accommodating style (P  =  .019). Midwest respondents selected the collaborating
      style more than others did (41.3% versus 25%) (P  =  .009). Competing conflict
      style correlated positively with openly aggressive behavior and bold
      communication but negatively with expressive and sympathetic communications.
      CONCLUSION: There are differences in behavior patterns among faculty, residents,
      and GME administrators with suggestions of ethnic and geographic influences.
      Correlation among instruments supported theoretical relationships of construct
      validity.

PMID- 22655140
TI  - Internal medicine physicians' knowledge of health care charges.
AB  - BACKGROUND: Concerns over the rising costs of health care have increased interest
      in educating residents about the cost impact of medical decisions. While many
      programs educate residents about the effectiveness of care, little is known about
      how well residents and faculty know charges of diagnostic tests or both groups'
      interest in this topic. METHODS: We surveyed internal medicine residents and
      faculty at an academic tertiary care hospital. Both groups rated their agreement
      with a series of statements about health care charges on a Likert scale of 1
      (strongly disagree) to 9 (strongly agree), and they estimated the charges for 15
      commonly ordered diagnostic tests. Estimates within 25% of the true charge were
      considered correct. The Wilcoxon rank sum test was used to compare responses
      between residents and faculty. RESULTS: Seventy of 126 eligible participants
      (56%) returned surveys. Participants showed poor knowledge of health care charges
      but expressed a desire to learn more. Physicians also felt that cost
      effectiveness should be considered when ordering diagnostic tests, although
      faculty members felt more strongly about this than did residents. In estimating
      the charges for diagnostic tests, less than a quarter of all responses were
      within 25% of the true charge. CONCLUSIONS: Internal medicine physicians poorly
      estimate the charges for diagnostic tests but have a strong desire to improve
      their knowledge, suggesting a possible intervention to improve the cost
      effectiveness of medical care.

PMID- 22655141
TI  - Senior pediatric residents as teachers for an innovative multidisciplinary mock
      code curriculum.
AB  - BACKGROUND: Resuscitation education for pediatric residents may be limited due to
      the low frequency of actual codes in children. Mock codes represent an
      opportunity to increase trainee education in acute resuscitations, and we
      designed a unique multidisciplinary mock code curriculum that uses senior
      pediatric residents as teachers. METHODS: A novel mock code curriculum was
      designed and integrated into an existing night-float rotation. Our 2-tiered
      curriculum not only focuses on improving teaching proficiency for resident
      educators (REs) but also includes separate goals to augment simulation-based
      resuscitation education for resident participants (RPs) and the multidisciplinary
      staff. RESULTS: Seventy-six residents (17 REs, 59 RPs) and more than 75 nurses
      have participated in the curriculum. After participation, 100% of residents felt
      that this curriculum would improve the quality of actual resuscitations, and 94%
      of RPs reported receiving valuable feedback. Comfort with teaching and feedback
      increased for REs (P < .05), and comfort in resuscitation and crisis resource
      management improved for RPs (P < .05). The nursing staff also felt that
      communication, teamwork, and collaboration improved due to implementation of this
      curriculum. CONCLUSIONS: A unique mock code curriculum can improve resident
      comfort with teaching, peer facilitation, feedback, and resuscitation. Curricular
      interventions of this nature may also be able to improve the balance between
      service and education within a residency training program. As we move toward a
      competency based training model within graduate medical education, further
      investigation is needed to link educational modifications of this nature to
      clinical outcomes and actual resident performance.

PMID- 22655142
TI  - Improving care in a resident practice for patients with diabetes.
AB  - BACKGROUND: Curricular redesign and introduction of the Chronic Care Model in our
      residency clinic during 2005-2007 achieved limited success in glycemic (glycated
      hemoglobin level [A(1c)]), lipid (low-density lipoprotein fraction [LDL]), and
      blood pressure (BP) control for patients with diabetes. INTERVENTION: Beginning
      in January 2008, ancillary staff performed previsit, protocol-driven reviews of
      medical records of patients with diabetes to identify those not at A(1c), LDL,
      and BP goals; inserted electronic prompts into the records regarding
      deficiencies; and obtained samples for A(1c) or lipid panel when needed. Faculty
      feedback regarding resident-specific panel reviews was added in May 2008, and
      point-of-care A(1c) testing was implemented in February 2009. METHODS: We
      conducted a 2-year retrospective study of all patients at our facility with
      diabetes mellitus, who had at least 1 visit during January to June 2008
      (baseline) and 1 visit during July to December 2009 (follow-up). Measures
      included the most current A(1c), LDL, and BP results. Paired outcome results were
      compared using the McNemar chi(2) test. RESULTS: A total of 522 patients with
      diabetes mellitus were seen during the baseline and follow-up periods, and 456
      patients (87.4%) had paired A(1c) results, with A(1c) < 7.0% for 138 of 456
      patients (30.3%) at baseline and 166 of 456 patients (36.4%) at follow-up (P  = 
      .011). For LDL, 460 patients (88.1%) had paired results, with LDL < 100 mg/dL for
      225 of 460 patients (48.9%) at baseline and 262 of 460 patients (57.0%) at follow
      up (P  =  .004). A total of 513 patients (98.3%) had paired BP results in which
      the BP < 130/80 mm Hg for 124 of 513 patients (24.2%) at baseline and for 188 of
      513 patients (36.6%) at follow-up (P < .001). There were 421 patients (80.7%)
      with paired results for all 3 measures, with 17 of 421 patients (4.0%) at goal at
      baseline and 41 of 421 patients (9.7%) at goal at follow-up (P  =  .001).
      CONCLUSION: The interventions resulted in statistically significant improvements
      in the proportion of patients with diabetes who attained goal for A(1c), LDL, and
      BP levels. Our redesign elements may be useful in enhancing resident education
      and in improving patient care.

PMID- 22655143
TI  - An interdisciplinary infection control education intervention: necessary but not
      sufficient.
AB  - BACKGROUND: Patient care environments are struggling to eradicate health care
      associated infections and studies of undergraduate and graduate medical trainees
      have revealed significant gaps in their performance of proper hand hygiene and
      aseptic technique (HH/AT), suggesting the need for improved curriculum. High
      reliability industries have provided a model using standardization of approach
      and interprofessional training, and both are particularly suited to the teaching
      and assessment of these life-saving skills. The Infection Control Education
      project is a grant-funded, multi-institutional pilot launched to improve the
      teaching and assessment of HH/AT in our community. METHODS: An interprofessional
      team of leaders and educators from 2 local hospital systems and 3 health colleges
      developed a 9-component "ICE PACK," which includes a unanimously endorsed,
      detailed HH/AT checklist. This teaching and assessment module was delivered to
      nursing/medical student and postgraduate year 1 resident/nurse intern pairs.
      Retention of checklist skills was retested 2 to 5 months after participation in
      the module. RESULTS: Learner pairs participating in the 2-hour module mastered
      the HH/AT checklist and rated the experience highly. Retention after several
      weeks was disappointingly low in 2 of the 3 participant groups. CONCLUSIONS: A
      community-wide HH/AT checklist was developed and an ICE PACK of materials created
      that is portable, standardizes the teaching and assessment of HH/AT skills, and
      is designed for interprofessional pairs of learners. Retention of checklist steps
      was disappointing in most of participant groups. Multiple, simultaneous
      strategies for improving compliance with infection control mandates appear
      necessary.

PMID- 22655144
TI  - Progress toward improving the quality of cardiac arrest medical team responses at
      an academic teaching hospital.
AB  - BACKGROUND: Internal medicine (IM) residents who undergo simulation-based
      advanced cardiac life support (ACLS) training are significantly more likely to
      manage actual events according to American Heart Association (AHA) standards than
      nontrained residents. How long ACLS skills are retained is unknown. METHODS: We
      conducted a retrospective case-control study of ACLS responses from January to
      June 2008 and reviewed medical records to assess adherence to AHA standards.
      Cases and controls are team responses to ACLS events divided into those directed
      by postgraduate year 2 (PGY-2) IM resident leaders versus those managed by PGY-3
      IM resident leaders. Residents in 2008 completed an educational program featuring
      deliberate practice in ACLS using a human patient simulator during their second
      year. Medical records of ACLS events were reviewed to assess adherence to AHA
      guidelines. We evaluated the effects of simulation training on quality of ACLS
      care during the 2008 period and in comparison with historical 2004 data. RESULTS:
      In 2008, 1 year after simulation training, PGY-3 residents showed the same
      adherence to AHA standards (88% [SD, 17%]) as that of PGY-2 residents who were
      newly simulator trained (86% [SD, 18%]) (P  =  .77). Previously, in 2004, PGY-2
      simulator-trained residents showed significantly higher adherence to AHA
      standards (68% [SD, 20%]) than nonsimulator-trained PGY-3 residents (44% [SD,
      20%]) (P < .001). All resident groups in 2008 outperformed their 2004 peers.
      CONCLUSIONS: Improved quality of ACLS care was maintained by 2008 PGY-3 simulator
      trained residents 1 year after training, likely due to skill retention rather
      than increased clinical experience, as a prior cohort of PGY-3 residents did not
      perform as well as PGY-2 residents in actual ACLS care. Our results confirm prior
      work regarding the impact of simulation-based education to improve the quality of
      actual patient care.

PMID- 22655145
TI  - A public health approach to pediatric residency education: responding to social
      determinants of health.
AB  - OBJECTIVE: To evaluate the impact of a public health approach to pediatric
      residency education on learner knowledge, skills, attitudes, beliefs, and career
      choice. BACKGROUND: Incorporating public health principles into traditional
      residency education can give pediatricians the population-oriented perspective to
      address social determinants of health. METHODS: The Community Health and Advocacy
      Training (CHAT) program is an educational intervention with a public health
      framework. From 2001-2007, 215 categorical pediatric residents and 37 residents
      in the CHAT program were evaluated by using an annual survey of community
      pediatrics exposure, knowledge, attitudes, and beliefs. American Board of
      Pediatrics (ABP) examination passage rates for both groups were also examined, as
      was career choice after graduation. RESULTS: While interns in both the
      categorical and CHAT programs scored similarly on attitudes, beliefs, skills, and
      knowledge of community pediatrics, the postgraduate level-3 (PL-3) year CHAT
      residents scored higher in attitudes (P < .001) and skills (P < .05). Exposure to
      both didactic (P < .05) and practical (P < .001) community pediatrics curricular
      experiences were higher for CHAT residents than for categorical residents. No
      significant differences between ABP examination scores were found for the 2
      groups, although 100% of CHAT graduates passed on the first try compared to 91%
      of categorical graduates during this time period. A greater percentage of CHAT
      graduates (82%) than categorical graduates (53%) reported pursuing careers in
      primary care. CONCLUSION: With a public health approach to residency education,
      residents gain the knowledge, attitudes, and skills to address child health
      problems from a population perspective. Participation in such a curriculum still
      resulted in high passage rates on the ABP examination.

PMID- 22655146
TI  - Evaluation of a case-based primary care pediatric conference curriculum.
AB  - BACKGROUND: Our goal was to assess the impact of a standardized residency
      curriculum in ambulatory pediatrics on residents' participation, satisfaction,
      and confidence. METHODS: A case-based curriculum for weekly primary care
      conference was developed to replace the existing free-form review of topics at
      the Yale Pediatrics Residency Program. Before the curricular switch, faculty
      preceptors and members of the academic year 2005-2006 intern class completed
      surveys designed to measure conference occurrence and resident attendance,
      participation, satisfaction, and confidence in clinical skills. One year after
      the curricular switch, identical surveys were completed by faculty preceptors and
      members of the academic year 2006-2007 intern class. RESULTS: Faculty surveys
      indicated that conferences took place significantly more often after the
      curricular switch. The number of residents at conference each day (3.18 vs 4.50;
      P < .01) and the percentage who actually spoke during conference (45% vs 82%, P <
      .01) significantly increased. There were 18 demographically similar interns in
      each of the 2 classes. Members of the academic year 2006-2007 intern class,
      having trained exclusively with the standardized curriculum, were significantly
      more likely to respond favorably to survey items about participation,
      satisfaction, and confidence. In addition, they were more likely to endorse
      survey items that reflected explicit goals of the standardized curriculum and the
      Accreditation Council for Graduate Medical Education core competencies.
      CONCLUSION: Implementation of a structured curriculum for ambulatory care
      improved interns' self-reported participation, satisfaction, and confidence. The
      primary care conference occurred more dependably after the curricular change, and
      improvements in attendance and participation were documented. Pediatric residency
      programs may make better use of conference time in the ambulatory setting through
      the use of structured, case-based educational material.

PMID- 22655147
TI  - Graduate medical education leadership development curriculum for program
      directors.
AB  - OBJECTIVE: Program director (PD) orientation to roles and responsibilities takes
      on many forms and processes. This article describes one institution's innovative
      arm of faculty development directed specifically toward PDs and associate PDs to
      provide institutional resources and information for those in graduate medical
      education leadership roles. METHODS: The designated institutional official
      created a separate faculty development curriculum for leadership development of
      PDs and associate PDs, modeled on the Association of American Medical Colleges
      GRA (Group on Resident Affairs) graduate medical education leadership development
      course for designated institutional officials. It consists of monthly 90-minute
      sessions at the end of a working day, for new and experienced PDs alike, with
      mentoring provided by experienced PDs. We describe 2 iterations of the
      curriculum. To provide ongoing support a longitudinal curriculum of special
      topics has followed in the interval between core curriculum offerings. RESULTS:
      Communication between PDs across disciplines has improved. The broad, inclusive
      nature allowed for experienced PDs to take advantage of the learning opportunity
      while providing exchange and mentorship through sharing of lessons learned. The
      participants rated the course highly and education process and outcome measures
      for the programs have been positive, including increased accreditation cycle
      lengths. CONCLUSION: It is important and valuable to provide PDs and associate
      PDs with administrative leadership development and resources, separate from
      general faculty development, to meet their role-specific needs for orientation
      and development and to better equip them to meet graduate medical education
      leadership challenges. This endeavor provides a foundational platform for
      designated institutional official and PD interactions to work on program building
      and improvement.

PMID- 22655148
TI  - Engaging senior residents as leaders: a novel structure for multiple chief roles.
AB  - BACKGROUND: The chief resident's role encompasses administrative, academic,
      educational, and social responsibilities and is traditionally filled by a small
      number of residents who are charged with various administrative and educational
      duties. These duties lay the groundwork that prepares chief residents to assume
      future leadership positions. INTERVENTION: We propose a new model for multiple
      chief residents. In this system, there are leadership roles for resident and
      medical student education, ultrasonography, resident research, and high-fidelity
      simulation in addition to the traditional administrative roles. This model can be
      modified to match the needs of a given program and the aptitudes of the senior
      residents. RESULTS: We describe the successful implementation of this model at
      our program, which has resulted in a progressive curriculum, increased resident
      leadership, and program ownership among the residents. CONCLUSIONS: Our
      intervention offers an alternative model for overcoming some of the limitations
      of the traditional chief resident model, including some chief residents who
      become overwhelmed by their duties and are discouraged from pursuing future
      leadership roles. It also has the potential to offer other senior residents with
      various skills and leadership abilities the opportunities to contribute to their
      program.

PMID- 22655149
TI  - Expanding educators' medical curriculum tool chest: minute papers as an
      underutilized option for obtaining immediate feedback.
AB  - BACKGROUND: One barrier to systematically assessing feedback about the content or
      format of teaching conferences in graduate medical education is the time needed
      to collect and analyze feedback data. Minute papers, brief surveys designed to
      obtain feedback in a concise format, have the potential to fill this gap.
      OBJECTIVES: To assess whether minute papers were a feasible tool for obtaining
      immediate feedback on resident conferences and to use minute papers, with one
      added question, to assess the usefulness of changing the format of resident
      morning report. METHODS: Minute papers were administered at the end of internal
      medicine morning report conferences before and after changing the traditional
      combined format (all residents) to a separate format (postgraduate year [PGY] 1
      met separately from PGY-2 and PGY-3 trainees). We collected information during 3
      months during 2 traditional sessions and 8 sessions in the format that separated
      PGY-1s (3 for PGY-1 and 5 for PGY-2 and PGY-3). Participants responded to an item
      rating the usefulness of the session and 3 open-ended questions. RESULTS:
      Trainees completed the forms in 2 to 3 minutes. Trainee assessment of the
      usefulness of internal medicine morning report appeared to increase after the
      change (4.09 versus 4.45 for PGY-1; 3.75 versus 4.38 for PGY-2 and PGY-3
      residents). CONCLUSIONS: Minute papers are practical instruments that provide
      manageable amounts of immediate feedback. In addition, minute papers can be
      adjusted slightly to help assess the impact of change. In that way, faculty can
      create an iterative process of feedback that models small cycles of change, a key
      quality improvement concept.

PMID- 22655150
TI  - Sleeping at home: a new model for a hospital teaching service.

PMID- 22655151
TI  - Developing a Cultural Consensus Analysis Based on the Internal Medicine
      Milestones (M-CCA).
AB  - A national task force identified domains and developmental milestones from the
      national competencies for resident training. Cultural Consensus Analysis (CCA) is
      a standard anthropological technique that can identify value conflicts. We
      created a CCA based on the internal medicine milestones (M-CCA) in 3 steps:
      converted the 38 domains into active statements; reduced the total number to 12
      by summarizing and combining; and simplified the wording. This M-CCA needs
      further validation, after which it may be useful for assessing the 6-competency
      model.

PMID- 22655152
TI  - Educational excellence in a crowded emergency department: consensus
      recommendations from the council of emergency medicine residency directors 2010.
AB  - OBJECTIVE: Emergency Department (ED) crowding is a major public health problem
      and one that has not been well studied for its effects on education. The
      objective of this article was to identify best-practice, consensus
      recommendations to help emergency medicine (EM) residency programs and faculty
      maintain educational excellence in an era of ED crowding. METHODS: A
      geographically diverse group of 37 clinician-educator leaders in EM convened at
      the 2010 Council of Emergency Medicine Residency Directors Academic Assembly. The
      participants discussed innovative ideas and solutions to address the many
      educational challenges that ED crowding poses. RESULTS: To cope with crowding,
      the consensus group identified 3 educational domains, focusing on the educator,
      the learner, and the institutional system. Core subthemes included optimizing
      teaching opportunities, providing alternative teaching approaches, and redefining
      what faculty and learners traditionally think of as teaching. An ED rotation
      provides ample opportunities for teaching not only about patient care and medical
      knowledge but also other Accreditation Council for Graduate Medical Education
      competencies, such as interpersonal and communication skills, professionalism,
      and system-based practice. CONCLUSIONS: Crowding in EDs poses educational
      challenges, but with some creativity, flexibility, and desire to make the most of
      a challenging situation, educational excellence is an achievable goal.

PMID- 22655153
TI  - Impact of a teaching rotation on residents' attitudes toward teaching: a 5-year
      study.
AB  - BACKGROUND: Residents play a tremendous role in educating medical students and
      other residents during their training. Many residency programs have thus
      instituted formal instruction on teaching. This 5-year study was conducted to
      quantitatively evaluate the impact of a teaching rotation on residents' attitudes
      towards teaching. METHODS: Residents participated in a 1-month teaching rotation,
      which included didactic sessions as well as protected time to practice their
      teaching skills. Before and after the rotation, residents anonymously filled out
      surveys regarding their attitudes towards teaching. Data were collected from 73
      residents from July 2004 to September 2009. The data were analyzed using a 2
      tailed t-test with independent variables and a 1-way ANOVA followed by a
      posttest. RESULTS: Four categories showed significant improvement, including
      feeling prepared to teach (P < .0001), having confidence in their teaching
      ability (P < .0001), being aware of their expectations as a teacher (P < .0001),
      and feeling that their anxiety about teaching was at a healthy level (P = .0037).
      There was an increase in the level of enthusiasm, but the P value did not reach a
      significant range (P = .12). The level of enthusiasm started high and was
      significantly higher on the pretest than every other tested category (P < .0001).
      Footnote c to Table 2 should read: P value as calculated using the Mann-Whitney U
      test [corrected]. CONCLUSIONS: Residents are enthusiastic about teaching, and
      their level of enthusiasm remains high following a teaching rotation. Residents
      feel more prepared to teach, more confident in their teaching ability, more aware
      of their expectations as a teacher, and less anxious about teaching following a
      formal teaching rotation.

PMID- 22655154
TI  - Patient Follow-up in an Urban Resident Continuity Clinic: An Initiative to
      Improve Scheduling Practices.
AB  - INTRODUCTION: Failure to schedule timely follow-up appointments may impair
      continuity and quality of care, especially for patients with low health literacy
      and unstable living situations. Resident continuity clinics face particular
      challenges in scheduling patient follow-up because of residents' complex
      schedules and limited time in clinic. METHODS: As part of a structured quality
      improvement curriculum, residents initiated discussions with clinical supervisors
      and clerical staff to evaluate and improve scheduling practices in an urban
      continuity clinic. The problem-solving process emphasized feasibility (rapid
      implementation/evaluation cycle, low time/resource burden) and measurable
      outcomes. These discussions led to design of a new scheduling form. We evaluated
      the short-term impact of awareness raising by comparing scheduling rates before
      (month 1) versus after (months 2-3) implementation, and of the form itself by
      randomly selecting 2 afternoon clinics to implement the new form, with a third
      serving as control. RESULTS: We analyzed all patient encounters over a 3-month
      period (n  =  910), excluding patients with a recommended follow-up interval of
      greater than 4 months. The proportion of appointments "never scheduled" (at 1
      month after provider-requested follow-up date) declined from 18.8% (95%
      confidence interval [CI], 14.5%-23.9%) in month 1 to 11.4% (CI, 8.1%-15.5%) in
      month 3. This proportion was significantly higher before than after
      implementation of the form (multivariable relative risk, 1.49; 95% CI, 1.08-2.03;
      P  =  .02), both in clinics that used and did not use the form (P  =  .93 for
      difference). CONCLUSIONS: We describe a model resident-led, team-based
      intervention that addressed core competencies in graduate medical education while
      improving outpatient scheduling practices.

PMID- 22655155
TI  - It all starts and ends with the program director.

PMID- 22655156
TI  - Nimble approaches to curriculum evaluation in graduate medical education.

PMID- 22655157
TI  - Teaching about costs in training programs: a complex topic.

PMID- 22655158
TI  - Easing International Medical Graduates' Entry Into US Training.

PMID- 22655159
TI  - An alternative mechanism for clinical medical subspecialties' accreditation and
      recognition in iraq and other developing countries.

PMID- 22655160
TI  - Patient safety education for residents-a colorado story.

PMID- 22655161
TI  - Incorporating patient- and family-centered care into resident education:
      approaches, benefits, and challenges.
AB  - PURPOSE: A design conference with participants from accredited programs and
      institutions was used to explore how the principles of patient- and family
      centered care (PFCC) can be implemented in settings where residents learn and
      participate in care, as well as identify barriers to PFCC and simple strategies
      for overcoming them. APPROACH: In September 2009, the Accreditation Council for
      Graduate Medical Education (ACGME) held a conference with 74 participants
      representing a diverse range of educational settings and a group of expert
      presenters and facilitators. Small group sessions explored the status of PFCC in
      teaching settings, barriers that need to be overcome in some settings, simple
      approaches, and the value of a national program and ACGME support. FINDINGS:
      Participants shared information on the state of their PFCC initiatives, as well
      as barriers to implementing PFCC in the learning environment. These emerged in 6
      areas: culture, the physical environment, people, time and other constraints,
      skills and capabilities, and teaching and assessment, as well as simple
      strategies to help overcome these barriers. Two Ishikawa (Fishbone) diagrams (one
      for barriers and one for simple strategies) make it possible to select strategies
      for overcoming particular barriers. CONCLUSIONS: A group of participants with a
      diversity of approaches to incorporating PFCC into the learning environment
      agreed that respectful communication with patients/families needs to be learned,
      supported, and continuously demanded of residents. In addition, for PFCC to be
      sustainable, it has to be a fundamental expectation for resident learning and
      attainment of competence. Participants concurred that improving the environment
      for patients concurrently improves the environment for learners.

PMID- 22655162
TI  - Hypertension in the elderly.
AB  - The elderly are the most rapidly growing population group in the world. Data
      collected over a 30-year period have demonstrated the increasing prevalence of
      hypertension with age. The risk of coronary artery disease, stroke, congestive
      heart disease, chronic kidney insufficiency and dementia is also increased in
      this subgroup of hypertensives. Hypertension in the elderly patients represents a
      management dilemma to cardiovascular specialists and other practioners. During
      the last years and before the findings of the Systolic Hypertension in Europe
      Trial were published, the general medical opinion considered not to decrease
      blood pressure values similarly to other younger patients, in order to avoid
      possible ischemic events and poor oxygenation of the organs (brain, heart,
      kidney). The aim of this review article is to highlight the importance of
      treating hypertension in aged population in order to improve their quality of
      life and lower the incidence of the cardiovascular complications.

PMID- 22655163
TI  - Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic
      complications in diabetes.
AB  - Mitochondrial DNA (mtDNA) is particularly prone to oxidation due to the lack of
      histones and a deficient mismatch repair system. This explains an increased
      mutation rate of mtDNA that results in heteroplasmy, e.g., the coexistence of the
      mutant and wild-type mtDNA molecules within the same mitochondrion. In diabetes
      mellitus, glycotoxicity, advanced oxidative stress, collagen cross-linking, and
      accumulation of lipid peroxides in foam macrophage cells and arterial wall cells
      may significantly decrease the mutation threshold required for mitochondrial
      dysfunction, which in turn further contributes to the oxidative damage of the
      diabetic vascular wall, endothelial dysfunction, and atherosclerosis.

PMID- 22655166
TI  - Clinically unrecognized mitral regurgitation is prevalent in lone atrial
      fibrillation.
AB  - AIM: To investigate the prevalence of clinically unrecognized mitral
      regurgitation (MR) in lone atrial fibrillation (AF). METHODS: We studied the
      prevalence and severity of MR by transesophageal echocardiography (TEE) in
      patients with "lone" AF as compared to a matched cohort of patients in normal
      sinus rhythm (NSR) undergoing TEE for other indications besides recognized
      valvular heart disease. RESULTS: A total of 157 subjects (57 in the AF group and
      100 in the NSR group) with structurally normal cardiac valves were included in
      the study. In the AF group, moderate MR or more was noted in 66% of the patients,
      mild MR in 18%, trace or no MR in 16%. In the control group, moderate MR was
      noted in 6% of patients, mild MR 31%, trace or no MR in 63 % of patients.
      Moderate MR or greater was significantly more prevalent in the AF group compared
      to the NSR group (66% vs 6%, P < 0.0001). CONCLUSION: Clinically unrecognized
      moderate MR is prevalent in "lone" AF -either as an etiologic factor leading to
      "lone" AF or developing after onset of AF.

PMID- 22655165
TI  - Investigation of cardiomyopathy using cardiac magnetic resonance imaging part 2:
      Rare phenotypes.
AB  - Cardiac magnetic resonance imaging (CMRI) has emerged as a useful tertiary
      imaging tool in the investigation of patients suspected of many different types
      of cardiomyopathies. CMRI images are now of a sufficiently robust quality to
      enable high spatial and temporal resolution image acquisition. This has led to
      CMRI becoming an effective non-invasive imaging tool for many cardiomyopathies.
      In this two-part review we outline the typical sequences used to image
      cardiomyopathy and present the imaging spectrum of cardiomyopathy. Part I focused
      on the current classification of cardiomyopathy, the basic CMRI sequences used in
      evaluating cardiomyopathy and the imaging spectrum of common phenotypes. Part II
      illustrates the imaging spectrum of the more rare phenotypes.

PMID- 22655167
TI  - Measuring luminal esophageal temperature during pulmonary vein isolation of
      atrial fibrillation.
AB  - AIM: To investigate the luminal esophageal temperature (LET) at the time of
      delivery of energy for pulmonary vein isolation (PVI). METHODS: This study
      included a total of 110 patients with atrial fibrillation who underwent their
      first PVI procedure in our laboratory between March 2010 and February 2011. The
      LET was monitored in all patients. We measured the number of times that LET
      reached the cut-off temperature, the time when LET reached the cut-off
      temperature, the maximum temperature (T max) of the LET, and the time to return
      to the original pre-energy delivery temperature once the delivery of energy was
      stopped. RESULTS: Seventy-eight patients reached the cut-off temperature. It took
      6 s at the shortest time for the LET to reach the cut-off temperature, and 216.5
      +/- 102.9 s for the temperature to return to the level before the delivery of
      energy. Some patients experienced a transient drop in the LET (TDLET) just before
      energy delivery. Ablation at these sites always produced a rise to the LET cut
      off temperature. TDLET was not observed at sites where the LET did not rise.
      Thus, the TDLET before the energy delivery was useful to distinguish a high risk
      of esophageal injury before delivery of energy. CONCLUSION: Sites with a TDLET
      before energy delivery should be ablated with great caution or, perhaps, not at
      all.

PMID- 22655164
TI  - Preventing radiocontrast-induced nephropathy in chronic kidney disease patients
      undergoing coronary angiography.
AB  - Radiocontrast-induced nephropathy (RCIN) is an acute and severe complication
      after coronary angiography, particularly for patients with pre-existing chronic
      kidney disease (CKD). It has been associated with both short- and long-term
      adverse outcomes, including the need for renal replacement therapy, increased
      length of hospital stay, major cardiac adverse events, and mortality. RCIN is
      generally defined as an increase in serum creatinine concentration of 0.5 mg/dL
      or 25% above baseline within 48 h after contrast administration. There is no
      effective therapy once injury has occurred, therefore, prevention is the
      cornerstone for all patients at risk for acute kidney injury (AKI). There is a
      small but growing body of evidence that prevention of AKI is associated with a
      reduction in later adverse outcomes. The optimal strategy for preventing RCIN has
      not yet been established. This review discusses the principal risk factors for
      RCIN, evaluates and summarizes the evidence for RCIN prophylaxis, and proposes
      recommendations for preventing RCIN in CKD patients undergoing coronary
      angiography.

PMID- 22655168
TI  - Cross-border quest: the reality and legality of transplant tourism.
AB  - Background. Transplant tourism is a phenomenon where patients travel abroad to
      purchase organs for transplants. This paper presents the results of a fieldwork
      study by describing the experiences of Dutch transplant professionals confronted
      by patients who allegedly purchased kidney transplants abroad. Second, it
      addresses the legal definition and prohibition of transplant tourism under
      national and international law. The final part addresses the legal implications
      of transplant tourism for patients and physicians. Methods. The study involved
      seventeen interviews among transplant physicians, transplant coordinators and
      policy-experts and a review of national and international legislation that
      prohibit transplant tourism. Results. All Dutch transplant centers are confronted
      with patients who undergo transplants abroad. The estimated total number is four
      per year. Transplant tourism is not explicitly defined under national and
      international law. While the purchase of organs is almost universally prohibited,
      transplant tourism is hardly punishable because national laws generally do not
      apply to crimes committed abroad. Moreover, the purchase of organs (abroad) is
      almost impossible to prove. Conclusions. Transplant tourism is a legally complex
      phenomenon that warrants closer research and dialogue. The legal rights and
      obligations of patients and physicians confronted with transplant tourism should
      be clarified.

PMID- 22655169
TI  - Evaluation of the medically complex living kidney donor.
AB  - Due to organ shortage and difficulties for availability of cadaveric donors,
      living donor transplantation is an important choice for having allograft. Live
      donor surgery is elective and easier to organize prior to starting dialysis
      thereby permitting preemptive transplantation as compared to cadaveric
      transplantation. Because of superior results with living kidney transplantation,
      efforts including the usage of "Medically complex living donors" are made to
      increase the availability of organs for donation. The term "Complex living donor"
      is probably preferred for all suboptimal donors where decision-making is a
      problem due to lack of sound medical data or consensus guidelines. Donors with
      advanced age, obesity, asymptomatic microhematuria, proteinuria, hypertension,
      renal stone disease, history of malignancy and with chronic viral infections
      consist of this complex living donors. This medical complex living donors
      requires careful evaluation for future renal risk. In this review we would like
      to present the major issues in the evaluation process of medically complex living
      kidney donor.

PMID- 22655171
TI  - Enhancing schistosomiasis control strategy for zimbabwe: building on past
      experiences.
AB  - Schistosoma haematobium and Schistosoma mansoni are prevalent in Zimbabwe to
      levels that make schistosomiasis a public health problem. Following three
      national surveys to map the disease prevalence, a national policy on control of
      schistosomiasis and soil transmitted helminths is being developed. This paper
      reviews the experiences that Zimbabwe has in the area of schistosomiasis control
      with a view to influence policy. A case study approach to highlight key
      experiences and outcomes was adopted. The benefits derived from intersectoral
      collaboration that led to the development of a model irrigation scheme that
      incorporates schistosomiasis control measures are highlighted. Similarly, the
      benefits of using plant molluscicides and fish and duck biological agents
      (Sargochromis codringtonii and Cairina moschata) are highlighted. Emphasis was
      also placed on the importance of utilizing locally developed water and sanitation
      technologies and the critical human resource base in the area of schistosomiasis
      developed over years. After synthesis of the case studies presented, it was
      concluded that while there is a need to follow the WHO recommended guidelines for
      schistosomiasis control it is important to develop a control strategy that is
      informed by work already done in the country. The importance of having a policy
      and local guidelines for schistosomiasis control is emphasized.

PMID- 22655170
TI  - Inflammation-Mediated Regulation of MicroRNA Expression in Transplanted
      Pancreatic Islets.
AB  - Nonspecific inflammation in the transplant microenvironment results in beta-cell
      dysfunction and death influencing negatively graft outcome. MicroRNA (miRNA)
      expression and gene target regulation in transplanted islets are not yet well
      characterized. We evaluated the impact of inflammation on miRNA expression in
      transplanted rat islets. Islets exposed in vitro to proinflammatory cytokines and
      explanted syngeneic islet grafts were evaluated by miRNA arrays. A subset of 26
      islet miRNAs was affected by inflammation both in vivo and in vitro. Induction of
      miRNAs was dependent on NF-kappaB, a pathway linked with cytokine-mediated islet
      cell death. RT-PCR confirmed expression of 8 miRNAs. The association between
      these miRNAs and mRNA target-predicting algorithms in genome-wide RNA studies of
      beta-cell inflammation identified 238 potential miRNA gene targets. Several genes
      were ontologically associated with regulation of insulin signaling and secretion,
      diabetes, and islet physiology. One of the most activated miRNAs was miR-21.
      Overexpression of miR-21 in insulin-secreting MIN6 cells downregulated endogenous
      expression of the tumor suppressor Pdcd4 and of Pclo, a Ca(2+) sensor protein
      involved in insulin secretion. Bioinformatics identified both as potential
      targets. The integrated analysis of miRNA and mRNA expression profiles revealed
      potential targets that may identify molecular targets for therapeutic
      interventions.

PMID- 22655172
TI  - Metal Ion Chelates as Surrogates of Nucleobases for the Recognition of Nucleic
      Acid Sequences: The Pd(2+) Complex of 2,6-Bis(3,5-dimethylpyrazol-1-yl)purine
      Riboside.
AB  - A 2,6-bis(3,5-dimethylpyrazol-1-yl)purine ribonucleoside has been prepared and
      incorporated as a conventionally protected phosphoramidite into a 9-mer 2'-O
      methyl oligoribonucleotide. According to 1H NMR spectroscopic studies, this
      nucleoside forms with Pd(2+) and uridine a ternary complex that is stable at a
      micromolar concentration range. CD spectroscopic studies on oligonucleotide
      hybridization, in turn, suggest that the Pd(2+) chelate of this artificial
      nucleoside, when incorporated in a 2'-O-methyl-RNA oligomer, is able to recognize
      thymine within an otherwise complementary DNA strand. The duplex containing
      thymidine opposite to the artificial nucleoside turned out to be somewhat more
      resistant to heating than its counterpart containing 2'-deoxycytidine in place of
      thymidine, but only in the presence of Pd(2+). According to UV-melting
      measurements, replacement of 2'-O-methyladenosine with the artificial nucleoside
      markedly enhances hybridization with a DNA target, irrespective of the identity
      of the opposite base and the presence of Pd(2+). With the thymidine containing
      DNA target, the T(m) value is 2-4 degrees C higher than with targets containing
      any other nucleoside opposite to the artificial nucleoside, but the dependence on
      Pd(2+) is much less clear than in the case of the CD studies.

PMID- 22655173
TI  - Obesity and trends in life expectancy.
AB  - Background. Increasing levels of obesity over recent decades have been expected
      to lead to an epidemic of diabetes and a subsequent reduction in life expectancy,
      but instead all-cause and cardiovascular-specific mortality rates have decreased
      steadily in most developed countries and life expectancy has increased. Methods.
      This paper suggests several factors that may be masking the effects of obesity on
      life expectancy. Results. It is possible that health and life expectancy gains
      could be even greater if it was not for the increasing prevalence of extreme
      obesity. It is also possible that the principal impact of obesity is on
      disability-free life expectancy rather than on life expectancy itself.
      Conclusion. If the principal impact of obesity were through disability-free life
      expectancy rather than on life expectancy itself, this would have substantial
      implications for the health of individuals and the future burden on the health
      care system.

PMID- 22655174
TI  - Evaluation of personal and built environment attributes to physical activity: a
      multilevel analysis on multiple population-based data sources.
AB  - Background. Studies have documented that built environment factors potentially
      promote or impede leisure time physical activity (LTPA). This study explored the
      relationship between multiple built environment factors and individual
      characteristics on LTPA. Methods. Multiple data sources were utilized including
      individual level data for health behaviors and health status from the Nevada
      Behavioral Risk Factor Surveillance System (BRFSS) and community level data from
      different data sources including indicators for recreation facilities, safety,
      air quality, commute time, urbanization, population density, and land mix level.
      Mixed model logistic regression and geographic information system (GIS) spatial
      analysis were conducted. Results. Among 6,311 respondents, 24.4% reported no LTPA
      engagement during the past 30 days. No engagement in LTPA was significantly
      associated with (1) individual factors: older age, less education, lower income,
      being obesity, and low life satisfaction and (2) community factors: more commute
      time, higher crime rate, urban residence, higher population density, but not for
      density and distance to recreation facilities, air quality, and land mix.
      Conclusions. Multiple data systems including complex population survey and
      spatial analysis are valuable tools on health and built environment studies.

PMID- 22655175
TI  - Understanding the Social Networks That Form within the Context of an Obesity
      Prevention Intervention.
AB  - Background. Antiobesity interventions have generally failed. Research now
      suggests that interventions must be informed by an understanding of the social
      environment. Objective. To examine if new social networks form between families
      participating in a group-level pediatric obesity prevention trial. Methods.
      Latino parent-preschool child dyads (N = 79) completed the 3-month trial. The
      intervention met weekly in consistent groups to practice healthy lifestyles. The
      control met monthly in inconsistent groups to learn about school readiness.
      UCINET and SIENA were used to examine network dynamics. Results. Children's mean
      age was 4.2 years (SD = 0.9), and 44% were overweight/obese (BMI >= 85th
      percentile). Parents were predominantly mothers (97%), with a mean age of 31.4
      years (SD = 5.4), and 81% were overweight/obese (BMI >= 25). Over the study, a
      new social network evolved among participating families. Parents selectively
      formed friendship ties based on child BMI z-score, (t = 2.08; P < .05). This
      reveals the tendency for mothers to form new friendships with mothers whose
      children have similar body types. Discussion. Participating in a group-level
      intervention resulted in new social network formation. New ties were greatest
      with mothers who had children of similar body types. This finding might
      contribute to the known inability of parents to recognize child overweight.

PMID- 22655176
TI  - Do overweight and obese individuals select a "moderate intensity" workload when
      asked to do so?
AB  - The purpose of this study was (1) to determine if overweight/obese individuals
      (age 26-50 y) would self-select moderate exercise intensity when asked to do so
      and (2) to determine how this self-selected workload compared to exercising at a
      workload (60% peak aerobic capacity) that is known to provide cardioprotective
      health benefits. Oxygen consumption (VO(2)) and energy expenditure were measured
      in 33 men/women (BMI >= 27 kg/m(2)) who completed two 30 min walking bouts: (1)
      self-selected walking pace on an indoor track and (2) prescribed exercise pace
      (60% VO(2) peak) on a treadmill. The data revealed that (1) the prescribed
      intensity was 6% higher than the self-selected pace and elicited a higher energy
      expenditure (P < 0.05) than the self-selected pace (+83 kJ); (2) overweight
      subjects walked at a slightly lower percentage of VO(2) peak than the obese
      subjects (P < 0.05); (3) men walked at a lower percentage of VO(2) peak than the
      women (P < 0.05). In conclusion when asked to walk at a moderate intensity,
      overweight/obese individuals tended to select a lower workload in the "moderate
      intensity" range which could be maintained for 30 min; however, a higher
      intensity which would be more cardioprotective could not be maintained for 30 min
      by most individuals.

PMID- 22655177
TI  - Novel resistant potato starches on glycemia and satiety in humans.
AB  - This study was designed to determine the efficacy of two novel type-four
      resistant starches (RS4) on postprandial glycemia and ratings of fullness.
      Volunteers (n = 10) completed completed five interventions designed to determine
      the glycemic and satiety (fullness) effects of the starches (38 g,) alone and
      when added on top of available carbohydrate. The dose of the starches provided 30
      g of resistant starch per treatment. The treatments were: commercial resistant
      starch added to water (PF-), noncommercial resistant starch added to water (PR-),
      dextrose solution (DEX, 50 g), and DEX with PenFibe starch (PF+), and DEX with
      the non-commercial starch added (PR+). Blood glucose was measured in the fasted
      state and following the randomly assigned treatments at 30, 45, 60, 90, and 120
      minutes post-consumption. A visual analog scale was used to determine fullness at
      each time point. There were no differences in the glucose incremental areas under
      the curve (iAUC) for PF+ and PR+ compared with DEX. The PF- and PR- treatments
      had decreased (P < 0.05) iAUCs for glucose compared with DEX, PF+, and PR+. There
      were no treatment differences for RoF. The dose (38 g) of starches did not to
      alter glucose responses when added on top of 50 g of dextrose.

PMID- 22655179
TI  - FK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitors.
AB  - Fetal hemoglobin (HbF) improves the clinical severity of sickle cell disease
      (SCD), therefore, research to identify HbF-inducing agents for treatment purposes
      is desirable. The focus of our study is to investigate the ability of FK228
      analogues to induce HbF using a novel KU812 dual-luciferase reporter system.
      Molecular modeling studies showed that the structure of twenty FK228 analogues
      with isosteric substitutions did not disturb the global structure of the
      molecule. Using the dual-luciferase system, a subgroup of FK228 analogues was
      shown to be inducers of HbF at nanomolar concentrations. To determine the
      physiological relevance of these compounds, studies in primary erythroid
      progenitors confirmed that JMA26 and JMA33 activated HbF synthesis at levels
      comparable to FK228 with low cellular toxicity. These data support our lead
      compounds as potential therapeutic agents for further development in the
      treatment of SCD.

PMID- 22655180
TI  - Hemin augments growth and hemoglobinization of erythroid precursors from patients
      with diamond-blackfan anemia.
AB  - Diamond-Blackfan anemia (DBA) is congenital pure red-cell anemia due to a
      differentiation block in erythroid precursors. The disease is commonly caused by
      mutations in genes for ribosomal proteins. Despite the identification of disease
      causal genes, the disease pathogenesis is not completely elucidated. The
      ribosomal abnormalities are assumed to inhibit globin translation which may lead
      to excess free heme, stimulating a generation of free radicals and thereby
      damaging the precursors. We studied the effect of hemin (heme chloride) on
      cultured human erythroid precursors and found that contrary to aforementioned
      hypothesis, although hemin moderately stimulated free radicals, it did not cause
      apoptosis or necrosis. In erythroid precursors derived from DBA patients, hemin
      significantly stimulated growth and hemoglobinization. Thus, heme toxicity is
      unlikely to play a role in the pathophysiology of most DBA cases. Moreover, its
      beneficial effect in culture suggests a therapeutic potential.

PMID- 22655178
TI  - Fetal programming of body composition, obesity, and metabolic function: the role
      of intrauterine stress and stress biology.
AB  - Epidemiological, clinical, physiological, cellular, and molecular evidence
      suggests that the origins of obesity and metabolic dysfunction can be traced back
      to intrauterine life and supports an important role for maternal nutrition prior
      to and during gestation in fetal programming. The elucidation of underlying
      mechanisms is an area of interest and intense investigation. In this perspectives
      paper we propose that in addition to maternal nutrition-related processes it may
      be important to concurrently consider the potential role of intrauterine stress
      and stress biology. We frame our arguments in the larger context of an
      evolutionary-developmental perspective that supports roles for both nutrition and
      stress as key environmental conditions driving natural selection and
      developmental plasticity. We suggest that intrauterine stress exposure may
      interact with the nutritional milieu, and that stress biology may represent an
      underlying mechanism mediating the effects of diverse intrauterine perturbations,
      including but not limited to maternal nutritional insults (undernutrition and
      overnutrition), on brain and peripheral targets of programming of body
      composition, energy balance homeostasis, and metabolic function. We discuss
      putative maternal-placental-fetal endocrine and immune/inflammatory candidate
      mechanisms that may underlie the long-term effects of intrauterine stress. We
      conclude with a commentary of the implications for future research and clinical
      practice.

PMID- 22655181
TI  - Sonographic and clinical features of upper extremity deep venous thrombosis in
      critical care patients.
AB  - Background-Aim. Upper extremity deep vein thrombosis (UEDVT) is an increasingly
      recognized problem in the critically ill. We sought to identify the prevalence of
      and risk factors for UEDVT, and to characterize sonographically detected thrombi
      in the critical care setting. Patients and Methods. Three hundred and twenty
      patients receiving a subclavian or internal jugular central venous catheter (CVC)
      were included. When an UEDVT was detected, therapeutic anticoagulation was
      started. Additionally, a standardized ultrasound scan was performed to detect the
      extent of the thrombus. Images were interpreted offline by two independent
      readers. Results. Thirty-six (11.25%) patients had UEDVT and a complete scan was
      performed. One (2.7%) of these patients died, and 2 had pulmonary embolism
      (5.5%). Risk factors associated with UEDVT were presence of CVC [(odds ratio (OR)
      2.716, P = 0.007)], malignancy (OR 1.483, P = 0.036), total parenteral nutrition
      (OR 1.399, P = 0.035), hypercoagulable state (OR 1.284, P = 0.045), and obesity
      (OR 1.191, P = 0.049). Eight thrombi were chronic, and 28 were acute. We describe
      a new sonographic sign which characterized acute thrombosis: a double hyperechoic
      line at the interface between the thrombus and the venous wall; but its clinical
      significance remains to be defined. Conclusion. Presence of CVC was a strong
      predictor for the development of UEDVT in a cohort of critical care patients;
      however, the rate of subsequent PE and related mortality was low.

PMID- 22655182
TI  - Does Death of a Family Member Moderate the Relationship between Religious
      Attendance and Depressive Symptoms? The HUNT Study, Norway.
AB  - Background. The death of a family member is a stressful life event and can result
      in an increased level of depressive symptoms. Previous American research has
      shown inverse relationships between religious involvement and depression.
      European investigations are few and findings inconsistent; different contexts may
      have an important influence on findings. We therefore investigated the
      relationship between attendance at church/prayer house and depressive symptoms,
      and whether this relationship was moderated by the death of a close family
      member, in Norway. Methods. A population-based sample from the Nord-Trondelag
      Health Study, Norway (HUNT 3, N = 37,981), was the population examined. Multiple
      regression and interaction tests were utilised. Results. Religious attendees had
      lower scores on depressive symptoms than non-attendees; death of a close family
      member moderated this relationship. The inverse relationships between attendance
      at church/prayer house and depressive symptoms were greater among those
      experiencing the death of an immediate family member in the last twelve months
      compared to those without such an experience, with men's decrease of depressive
      symptoms more pronounced than women's. Conclusion. In a population-based study in
      Norway, attendance at church/prayer house was associated with lower depressive
      symptoms, and the death of a close relative and gender moderated this
      relationship.

PMID- 22655183
TI  - The role of preoperative bilateral breast magnetic resonance imaging in patient
      selection for partial breast irradiation in ductal carcinoma in situ.
AB  - Purpose. Women with ductal carcinoma in situ (DCIS) are often candidates for
      breast-conserving therapy, and one option for radiation treatment is partial
      breast irradiation (PBI). This study evaluates the use of preoperative breast
      magnetic resonance imaging (MRI) for PBI selection in DCIS patients. Methods.
      Between 2002 and 2009, 136 women with newly diagnosed DCIS underwent a
      preoperative bilateral breast MRI at Mayo Clinic in Florida. One hundred
      seventeen women were deemed eligible for PBI by the NSABP B-39 (National Surgical
      Adjuvant Breast and Bowel Project, Protocol B-39) inclusion criteria using
      physical examination, mammogram, and/or ultrasound. MRIs were reviewed for their
      impact on patient eligibility, and findings were pathologically confirmed.
      Results. Of the 117 patients, 23 (20%) were found ineligible because of
      pathologically proven MRI findings. MRI detected additional ipsilateral breast
      cancer in 21 (18%) patients. Of these women, 15 (13%) had more extensive disease
      than originally noted before MRI, and 6 (5%) had multicentric disease in the
      ipsilateral breast. In addition, contralateral breast cancer was detected in 4
      (4%). Conclusions. Preoperative breast MRI altered the PBI recommendations for
      20% of women. Bilateral breast MRI should be an integral part of the preoperative
      evaluation of all patients with DCIS being considered for PBI.

PMID- 22655184
TI  - Intraductal proliferative lesions of the breast-terminology and biology matter:
      premalignant lesions or preinvasive cancer?
AB  - Morphological criteria for the diagnosis of intraductal proliferative lesions of
      the breast have been an object of research and much controversy, and its
      terminology is rather confusing. Knowledge of the molecular aspects of this
      disease probably necessitates further research to clarify if these entities can
      be identified as breast cancer precursors or as a malignant preinvasive disease.
      These issues are of great interest not only for their biological implications,
      but also to the clinician who must understand the disease and direct therapies.
      Molecular studies have shown that epitheliosis (usual ductal hyperplasia) is not
      monoclonal, while malignant lesions (atypical ductal hyperplasia, flat epithelial
      atypia, low-grade and high-grade intraductal carcinoma) constantly show these
      characteristics. These malignant lesions, classified with a DIN grading system
      (ductal intraepithelial neoplasia), are not obligate precursors of invasive
      ductal carcinoma and do not represent different evolving grades in a linear model
      of cancerogenesis. Breast cancerogenesis probably has different pathways with
      different morphologic precursors.

PMID- 22655185
TI  - No excess mortality in patients aged 50 years and older who received treatment
      for ductal carcinoma in situ of the breast.
AB  - Background. The incidence of ductal carcinoma in situ (DCIS) has increased at a
      fast rate.The aim of this study was to assess the incidence and treatment in the
      Netherlands and estimate the excess mortality risk of DCIS. Methods. From the
      Netherlands Cancer Registry, adult female patients (diagnosed 1997-2005) with
      DCIS were selected. Treatment was described according to age. Relative mortality
      at 10 years of follow-up was calculated by dividing observed mortality over
      expected mortality. Expected mortality was calculated using the matched Dutch
      general population. Results. Overall, 8421 patients were included in this study.
      For patients aged 50-64, and 65-74 an increase in breast-conserving surgery was
      observed over time (P < 0.001). For patients over 75 years of age, 8.0% did not
      undergo surgery; this percentage remained stable over time (P = 0.07). Overall,
      treated patients aged >50 years experienced no excess mortality regardless of
      treatment (relative mortality 1.0). Conclusion. The present population-based
      study of almost 8500 patients showed no excess mortality in surgically treated
      women over 50 years with DCIS.

PMID- 22655186
TI  - Radiotherapy after conservative surgery in ductal carcinoma in situ of the
      breast: a review.
AB  - Several large prospective and retrospective studies have demonstrated excellent
      long-term outcomes after breast conservative treatment with radiation in invasive
      breast cancer. Breast-conserving surgery (BCS) followed by radiotherapy (RT) is
      an accepted management strategy for patients with DCIS. Adding radiation
      treatment after conservative surgery enables to reduce, without any significant
      risks, the rate of local recurrence (LR) by approximately 50% in retrospective
      and randomized clinical trials. As about 50% of LRs are invasive and have a
      negative psychological impact, minimizing recurrence is important. Local and
      local-regional recurrences after initial breast conservation treatment with
      radiation can be salvaged with high rates of survival and freedom from distant
      metastases.

PMID- 22655187
TI  - Horizontal violence and the quality and safety of patient care: a conceptual
      model.
AB  - For many years, nurses in international clinical and academic settings have
      voiced concern about horizontal violence among nurses and its consequences.
      However, no known framework exists to guide research on the topic to explain
      these consequences. This paper presents a conceptual model that was developed
      from four theories to illustrate how the quality and safety of patient care could
      be affected by horizontal violence. Research is needed to validate the new model
      and to gather empirical evidence of the consequences of horizontal violence on
      which to base recommendations for future research, education, and practice.

PMID- 22655188
TI  - Designing and implementing an ambulatory oncology nursing peer preceptorship
      program: using grounded theory research to guide program development.
AB  - Having enough staff to provide high-quality care to cancer patients will become a
      growing issue across Canada over the next decades. Statistical predictions
      indicate that both the number of new diagnoses and the prevalence of cancer will
      increase dramatically in the next two decades. When combining these trends with
      the simultaneous trend toward health human resource shortage in Canada, the
      urgency of assuring we have adequate staff to deliver cancer care becomes clear.
      This research study focuses directly on oncology nurses. Guided by the grounded
      theory methodology, this research study aims to formulate a strategic, proactive
      peer preceptorship program through a four-phased research process. The goal of
      this research is to develop a program that will support experienced staff members
      to fully implement their role as a preceptor to new staff, to facilitate
      effective knowledge transfer between experienced staff to the new staff members,
      and to assure new staff members are carefully transitioned and integrated into
      the complex ambulatory cancer care workplaces. In this article, the data from the
      first phase of the research project will be explored specifically as it relates
      to establishing the foundation for the development of a provincial ambulatory
      oncology nursing peer preceptorship program.

PMID- 22655189
TI  - Nurse faculty enrichment and competency development in oral-systemic health.
AB  - Nurses are positioned to play a significant role in oral health promotion and
      disease prevention across the life cycle. Oral health has not been a high
      priority in nursing practice, and educating nurses about oral health has been
      inadequate particularly regarding the interrelationship between oral health and
      overall health. The first step for developing a nursing workforce with core
      competencies in oral health promotion and disease prevention is to prepare nurse
      faculty with the requisite knowledge, skills, attitudes, and best practices in
      oral-systemic health. The purpose of this paper is to present Smiles for Life: A
      National Oral Health Curriculum as a knowledge framework that nurse faculty can
      use for faculty enrichment and competency development in oral health across the
      life cycle. A variety of teaching-learning strategies and resources are provided
      to assist nurse faculty with integrating oral-systemic health into existing
      nursing curricula.

PMID- 22655190
TI  - Single-port transumbilical laparoscopic appendectomy: a preliminary multicentric
      comparative study in 87 patients with acute appendicitis.
AB  - Introduction. Laparoscopic appendectomy (LA) has been performed in many
      approaches such as open, laparoscopic and recently Single Port Access (SPAA). In
      order to elucidate its potential advantages, we compared the two laparoscopic
      approaches. Methods. 87 patients were included in a multicentric study for
      suspected appendicitis in order to perform (SPAA) appendectomy or laparoscopic
      appendectomy (LA). All outcomes, including blood loss, operative time,
      complications, and length of stay and pain were recorded prospectively. Results.
      There were 46 patients in the SPAA group and 41 in the LAG with a mean operative
      time of 40,4 minutes in the SPAA group and 35,0 minutes in the LA group. Only one
      patient was converted to an open approach. We described only 2 complications.
      Pain was graded 2,8 in the SPAA group and 2,9 in the LA group, according to the
      AVS after 24 hours. Patients in the SPAA Group were more satisfied (7,5 versus
      6,9) (P < 0.05). Same results were found for the cosmetic result (8,6 versus 7,4)
      (P < 0.05). Conclusion. Using the single port approach feasible and safe. The
      true benefit of the technique should be assessed by new randomised controlled
      trials.

PMID- 22655191
TI  - Complications of blepharoplasty: prevention and management.
AB  - Blepharoplasty is an operation to modify the contour and configuration of the
      eyelids in order to restore a more youthful appearance. The surgery involves
      removing redundant skin, fat, and muscle. In addition, supporting structures such
      as canthal tendons are tightened. Other conditions such as ptosis, brow ptosis,
      entropion, ectropion, or eyelid retraction may also need to be corrected at the
      time a blepharoplasty is performed to ensure the best functional and aesthetic
      result. Due to the complexity and intricate nature of eyelid anatomy,
      complications do exist. In addition to a thorough pre operative assessment and
      meticulous surgical planning, understanding the etiology of complications is key
      to prevention. Finally, management of complications is just as important as
      surgical technique.

PMID- 22655192
TI  - Everolimus-Eluting versus Paclitaxel-Eluting Stents in Percutaneous Coronary
      Intervention: Meta-Analysis of Randomized Trials.
AB  - Background. Individual randomized trials have suggested that everolimus-eluting
      stents may have improved clinical outcomes compared to paclitaxel-eluting stents,
      but individual trials are underpowered to examine outcomes such as mortality and
      very late stent thrombosis. Methods. Medline, Cochrane, and conference
      proceedings were searched for randomized trials comparing everolimus versus
      paclitaxel-eluting stents for percutaneous coronary intervention. Results. 6792
      patients were included from 4 randomized controlled trials. Stent thrombosis was
      reduced with everolimus stents versus paclitaxel stents (0.7% versus 2.3%; OR:
      0.32; CI: 0.20-0.51; P < 0.00001). The reductions in stent thrombosis were
      observed in (i) early stent thrombosis (within 30 days) (0.2% versus 0.9%; OR:
      0.24; P = 0.0005), (ii) late (day 31-365) (0.2% versus 0.6%; OR: 0.32; P = 0.01),
      and (iii) very late stent thrombosis (>365 days) (0.2% versus 0.8%; OR: 0.34; P =
      0.009). The rates of cardiovascular mortality were 1.2% in everolimus group and
      1.6% in paclitaxel group (OR: 0.85; P = 0.43). Patients receiving everolimus
      eluting stents had significantly lower myocardial infarction events and target
      vessel revascularization as compared to paclitaxel-eluting stents.
      Interpretation. Everolimus compared to paclitaxel-eluting stents reduced the
      incidence of early, late, and very late stent thrombosis as well as target vessel
      revascularization.

PMID- 22655193
TI  - An IMS/ATP Assay for the Detection of Mycobacterium tuberculosis in Urine.
AB  - Background. Although sputum smears are the gold standard for diagnosis of
      tuberculosis, sensitivity in HIV/TB coinfection cases is low, indicating a need
      for alternative methods. Urine is being increasingly evaluated. Materials and
      Methods. A novel method for detecting Mycobacterium tuberculosis (MTB) in
      synthetic urine using a combined IMS/ATP assay was evaluated. Preliminary work
      established standard ATP conditions and the sensitivity and specificity of the
      MTB antibody. Eighty-four blinded samples in four replicate assays were evaluated
      for the presence of MTB using labeled immunomagnetic beads for capture. Beads
      were separated, washed, and resuspended in broth and added to a microtiter plate.
      Bioluminescent output was measured and signal-to-noise ratios were calculated.
      All samples were plated on Middlebrook 7H10 agar or trypticase soy agar to
      determine limit of detection and recoveries. Results and Conclusions. MTB was
      distinguished from common bacteriuria isolates and other nontarget bacteria by
      its ATP results. IMS/ATP successfully detected 19 of 28 samples of MTB in
      synthetic urine with a limit of detection of 10(4) CFU/ml. Sensitivity and
      specificity were 67.9% and 82.1%, respectively. This assay offers a possible
      rapid screening method for HIV-positive patients with suspected coinfection to
      improve MTB diagnosis.

PMID- 22655194
TI  - Effect and safety of mycophenolate mofetil or sodium in systemic sclerosis
      associated interstitial lung disease: a meta-analysis.
AB  - Background. Interstitial lung disease (ILD) is the most common complication of
      systemic sclerosis (SSc) with treatment ineffective. OBJECTIVE: The aim of this
      meta-analysis was to provide an estimate of the safety and efficacy profile of
      Mycophenolate Mofetil (MMF) or sodium (MMS) in SSc-ILD patients. Materials and
      Methods. All studies were reviewed systematically. The main end-points were
      safety and efficacy profile as estimated by forced vital capacity (FVC)% and
      diffusion capacity of the lung for carbon monoxide (DL(CO))% of the predicted
      normal value (%pred.) before and after treatment in patients with SSc-ILD.
      Quality assessment and data extraction were performed independently by two
      reviewers. Results. Seventeen studies were reviewed systematically. Six studies,
      one prospective, were eligible for analysis encompassing 69 patients, including
      10 subjects from our, yet unpublished, retrospective study. There was no
      statistically significant difference in both efficacy outcomes of interest,
      including FVC% pred. (weighted mean difference 1.48, 95% confidence interval
      (CI): -2.77 to 5.72, P = 0.49) and DL(CO) % pred. (weighted mean difference 
      0.83, 95% CI: -4.75 to 3.09, P = 0.93). No cases of clinically significant side
      effects were documented. Conclusions. Meta-analysis data suggest that MMF is a
      safe therapeutic modality which was associated with functional stabilization in
      patients with SSc-ILD.

PMID- 22655195
TI  - Persistent pulmonary hypertension of non cardiac cause in a neonatal intensive
      care unit.
AB  - Parenchymal lung diseases are the main cause of persistent pulmonary hypertension
      of the newborn (PPHN). We aimed to assess the non cardiac conditions associated
      to PPHN in the newborn and the survival rate over the last 15 years, at our
      center. A retrospective chart review of the neonates admitted for PPHN from 1996
      to 2010 was performed. New therapies were introduced in 2003, and the survival
      rates between two periods (1996-2002 and 2003-2010) were compared. Out of 6750
      newborns, 78 (1.1%) had the diagnosis of PPHN of non cardiac cause. The most
      prevalent causes were associated to pulmonary hypoplasia (30.7%), infection
      (24.3%), and aspiration syndromes (15.3%). Many other causes were identified in
      33.3%. The overall survival rate was 68%. There was a significant difference on
      survival rates between the two periods (1996-2002 = 63.8% and 2003-2010 = 71.4%,
      P = 0.04). Our study showed a myriad of non cardiac aetiologies for PPHN of the
      newborn, most of them related to lung disease or lung hypoplasia. We observed an
      improvement in survival rate since 2003, which was associated to the use of new
      therapies.

PMID- 22655196
TI  - Intraoperative image guidance in neurosurgery: development, current indications,
      and future trends.
AB  - Introduction. As minimally invasive surgery becomes the standard of care in
      neurosurgery, it is imperative that surgeons become skilled in the use of image
      guided techniques. The development of image-guided neurosurgery represents a
      substantial improvement in the microsurgical treatment of tumors, vascular
      malformations, and other intracranial lesions. Objective. There have been
      numerous advances in neurosurgery which have aided the neurosurgeon to achieve
      accurate removal of pathological tissue with minimal disruption of surrounding
      healthy neuronal matter including the development of microsurgical, endoscopic,
      and endovascular techniques. Neuronavigation systems and intraoperative imaging
      should improve success in cranial neurosurgery. Additional functional imaging
      modalities such as PET, SPECT, DTI (for fiber tracking), and fMRI can now be used
      in order to reduce neurological deficits resulting from surgery; however the
      positive long-term effect remains questionable for many indications. Method.
      PubMed database search using the search term "image guided neurosurgery." More
      than 1400 articles were published during the last 25 years. The abstracts were
      scanned for prospective comparative trials. Results and Conclusion. 14
      comparative trials are published. To date significant data amount show advantages
      in intraoperative accuracy influencing the perioperative morbidity and long-term
      outcome only for cerebral glioma surgery.

PMID- 22655197
TI  - Care-Seeking Pattern among Persons with Depression and Anxiety: A Population
      Based Study in Sweden.
AB  - Background. In primary care, a vast majority of patients affected with depression
      and anxiety present with somatic symptoms. Detection rate of psychiatric symptoms
      is low, and knowledge of factors influencing care seeking in persons affected by
      depressive and anxiety disorders on a population level is limited. Objective.
      This study aims to describe if persons, affected by depression and anxiety
      disorders, seek care and which type of care they seek as well as factors
      associated with care seeking. Method. Data derives from a longitudinal population
      based study of mental health conducted in the Stockholm County in 1998-2010 and
      the present study includes 8387 subjects. Definitions of anxiety and depressive
      disorders were made according to DSM-IV criteria, including research criteria,
      using validated diagnostic scales. 2026 persons (24%) fulfilled the criteria for
      any depressive or anxiety disorder. Results. Forty-seven percent of those
      affected by depression and/or anxiety had been seeking care for psychological
      symptoms within the last year. A major finding was that seeking care for
      psychological symptoms was associated with having treatment for somatic problems.
      Conclusions. As a general practitioner, it is of great importance to increase
      awareness of mild mental illness, especially among groups that might be less
      expected to be affected.

PMID- 22655198
TI  - Association of TCTP with centrosome and microtubules.
AB  - Translationally Controlled Tumour Protein (TCTP) associates with microtubules
      (MT), however, the details of this association are unknown. Here we analyze the
      relationship of TCTP with MTs and centrosomes in Xenopus laevis and mammalian
      cells using immunofluorescence, tagged TCTP expression and immunoelectron
      microscopy. We show that TCTP associates both with MTs and centrosomes at spindle
      poles when detected by species-specific antibodies and by Myc-XlTCTP expression
      in Xenopus and mammalian cells. However, when the antibodies against XlTCTP were
      used in mammalian cells, TCTP was detected exclusively in the centrosomes. These
      results suggest that a distinct pool of TCTP may be specific for, and associate
      with, the centrosomes. Double labelling for TCTP and gamma-tubulin with immuno
      gold electron microscopy in Xenopus laevis oogonia shows localization of TCTP at
      the periphery of the gamma-tubulin-containing pericentriolar material (PCM)
      enveloping the centriole. TCTP localizes in the close vicinity of, but not
      directly on the MTs in Xenopus ovary suggesting that this association requires
      unidentified linker proteins. Thus, we show for the first time: (1) the
      association of TCTP with centrosomes, (2) peripheral localization of TCTP in
      relation to the centriole and the gamma-tubulin-containing PCM within the
      centrosome, and (3) the indirect association of TCTP with MTs.

PMID- 22655199
TI  - Reversible masking using low-molecular-weight neutral lipids to achieve optimal
      targeted delivery.
AB  - Intravenous injection of therapeutics is required to effectively treat or cure
      metastatic cancer, certain cardiovascular diseases, and other acquired or
      inherited diseases. Using this route of delivery allows potential uptake in all
      disease targets that are accessed by the bloodstream. However, normal tissues and
      organs also have the potential for uptake of therapeutic agents. Therefore,
      investigators have used targeted delivery to attempt delivery solely to the
      target cells; however, use of ligands on the surface of delivery vehicles to
      target specific cell surface receptors is not sufficient to avoid nonspecific
      uptake. PEGylation has been used for decades to try to avoid nonspecific uptake
      but suffers from many problems known as "The PEGylation Dilemma." We have solved
      this dilemma by replacing PEGylation with reversible masking using low-molecular
      weight neutral lipids in order to achieve optimal-targeted delivery solely to
      target cells. Our paper will focus on this topic.

PMID- 22655200
TI  - Selection of a MCF-7 Breast Cancer Cell Subpopulation with High Sensitivity to IL
      1beta: Characterization of and Correlation between Morphological and Molecular
      Changes Leading to Increased Invasiveness.
AB  - Cancer and inflammation are closely related in tumor malignancy prognosis. Breast
      cancer MCF-7 cells have a poor invasive phenotype, although, under IL-1beta
      stimulus, acquire invasive features. Cell response heterogeneity has precluded
      precise evaluation of the malignant transition. MCF-7A3 cells were selected for
      high sensitivity to IL-1beta stimulus, uniform expression of CXCR4, and stability
      of IL1-RI. Structural changes, colony formation ability, proliferation rate,
      chemotaxis, Matrigel invasion, E-cadherin mRNA expression and protein
      localization were determined in these cells and in MCF-7 parental cells under the
      stimulus of IL-1beta. Selected MCF-7A3 cells showed a uniform response to IL
      1beta stimulation increasing features of invasive cells such as scattering,
      colony formation, proliferation, chemokinesis and invasion. Basal expression of E
      cadherin mRNA was higher, and IL-1beta stimulus had no further effect at early
      times of cytokine exposure. Total E-cadherin levels remained unchanged in
      parental cells, whereas levels decreased, as MCF-7A3 cells became fibroblastoid
      or scattered. Triton X-100 soluble/insoluble E-cadherin ratios were highly
      increased in these cells, while, in MCF-7pl cells, ratios could not be correlated
      with morphology changes. MCF-7A3 cells uniform response to IL-1beta allowed
      characterization of changes induced by the cytokine that had not been assessed
      when using heterogeneous cell lines.

PMID- 22655201
TI  - Biomarkers for hepatocellular carcinoma.
AB  - The hepatocellular carcinoma (HCC) is one of the most common malignant tumors and
      carries a poor survival rate. The management of patients at risk for developing
      HCC remains challenging. Increased understanding of cancer biology and
      technological advances have enabled identification of a multitude of
      pathological, genetic, and molecular events that drive hepatocarcinogenesis
      leading to discovery of numerous potential biomarkers in this disease. They are
      currently being aggressively evaluated to establish their value in early
      diagnosis, optimization of therapy, reducing the emergence of new tumors, and
      preventing the recurrence after surgical resection or liver transplantation.
      These markers not only help in prediction of prognosis or recurrence but may also
      assist in deciding appropriate modality of therapy and may represent novel
      potential targets for therapeutic interventions. In this paper, a summary of most
      relevant available data from published papers reporting various tissue and serum
      biomarkers involved in hepatocellular carcinoma was presented.

PMID- 22655202
TI  - Surgical treatment of articular cartilage defects in the knee: are we winning?
AB  - Articular cartilage (AC) injury is a common disorder. Numerous techniques have
      been employed to repair or regenerate the cartilage defects with varying degrees
      of success. Three commonly performed techniques include bone marrow stimulation,
      cartilage repair, and cartilage regeneration. This paper focuses on current level
      of evidence paying particular attention to cartilage regeneration techniques.

PMID- 22655203
TI  - Malocclusion Pattern (Angle's) in Mauritian Orthodontic Patients.
AB  - The aim of the study was to assess the pattern of malocclusion in different
      ethnic group of Mauritian population visiting the Orthodontic Department at
      Mauras College of Dentistry and Hospital, Republic of Mauritius. The study
      population comprised of 624 patients who visited the orthodontic department
      during 2010. The clinical examination was conducted by a well-calibrated
      orthodontist. The data were recorded in the case sheets and was analyzed for
      presence of angles class I, class II, and class III malocclusion in both male and
      female patients of Asian, African, Caucasian, and Chinese ethnicity aged 5-55
      years. Malocclusion was found to be high in females compared to males. 414
      patients (150 male + 264 female) presented with class I, 182 patients (52 male +
      130 female) presented with class II, and 28 patients (12 male + 16 female)
      presented with class III. Asian ethnic group were more affected and patient
      seeking orthodontic treatment was high in 11-15 years age group.

PMID- 22655204
TI  - Correlation between Calcitonin Levels and [(18)F]FDG-PET/CT in the Detection of
      Recurrence in Patients with Sporadic and Hereditary Medullary Thyroid Cancer.
AB  - Purpose. Measurement of serum calcitonin is important in the followup of patients
      with medullary thyroid carcinoma (MTC) and reliably reflects the presence of the
      disease. This is the largest study so far in bibliography investigating the
      diagnostic accuracy of combined [(18)F]FDG-PET/CT in patients with MTC and
      elevated calcitonin levels. Methods. Between February 2007 and February 2011, 59
      [(18)F]FDG-PET/CT were performed on 51 patients with MTC and elevated calcitonin
      levels for localization of recurrent disease. Conventional morphologic imaging
      methods were negative or showed equivocal findings. Results. Among the 59
      [(18)F]FDG-PET/CT, 29 were positive (26 had true-positive and 3 false-positive
      findings) and 30 negative. The overall per-patient sensitivity of [(18)F]FDG
      PET/CT was 44.1%. Using as cut-off point the calcitonin value of 1000 pg/ml, in
      patients with calcitonin exceeding this value, sensitivity raised to 86.7%. The
      overall sensitivity of [(18)F]FDG-PET/CT was lower (23%) in patients with MEN IIA
      syndrome. Conclusion. The findings of this paper show that [(18)F]FDG-PET/CT is
      valuable for the detection of recurrence in patients with highly elevated
      calcitonin levels, >1000 pg/mL, but in patients with lower calcitonin levels, its
      contribution is questionable. Also, there is evidence that the sensitivity of
      [(18)F]FDG-PET/CT is lower in patients with MTC as part of MEN IIA syndrome.

PMID- 22655205
TI  - Phase II Study of Gemcitabine and Docetaxel Combination in Patients with
      Previously Treated Recurrent or Metastatic Squamous Cell Carcinoma of the Head
      and Neck.
AB  - Purpose. To explore the safety and efficacy of gemcitabine and docetaxel (GEMDOC)
      in previously treated patients with recurrent or metastatic squamous cell
      carcinoma of the head and neck (SCCHN). Patients and Methods. Patients with
      advanced SCCHN previously pretreated with one or two lines of palliative
      chemotherapy were treated with gemcitabine and docetaxel until disease
      progression. Results. Thirty-six patients were enrolled, and 29 were response
      evaluable. 16 (55%) experienced clinical benefit (response or stable disease).
      Six (21%) patients achieved partial response (PR), none achieved complete
      response (CR), and the overall response rate (ORR) was 21% (95% CI: 0.10-0.38).
      Ten (28%) patients had stable disease. The median response duration (RD) for the
      6 PR patients was 3.2 months (80% CI: 2.0-6.1 months). Median overall survival
      was 4.2 months (95% CI: 2.4-7.0 months). Among the 33 treated patients: 13 (39%)
      patients had grade 3-4 anemia, 10 (30%) had grade 3-4 neutropenia. Conclusion.
      The study drugs were relatively safe, and the clinical benefit (PR + SD) rate was
      55%. However, the efficacy objective for this regimen was not met. Given the good
      safety profile, further investigation of this regimen with the addition of a
      targeted agent may lead to better efficacy.

PMID- 22655207
TI  - Robotic colorectal surgery: a systematic review.
AB  - Aim. Robotic colorectal surgery may be a way to overcome the limitations of
      laparoscopic surgery. It is an emerging field; so, we aim in this paper to
      provide a comprehensive and data analysis of the available literature on the use
      of robotic technology in colorectal surgery. Method. A comprehensive systematic
      search of electronic databases was completed for the period from 2000 to 2011.
      Studies reporting outcomes of robotic colorectal surgery were identified and
      analyzed. Results. 41 studies (21 case series, 2 case controls, 13 comparative
      studies 1 prospective comparative, 1 randomized trial, 3 retrospective analyses)
      were reviewed. A total of 1681 patients are included in this paper; all of them
      use Da Vinci except 2 who use Zeus. Short-term outcome has been evaluated with 0
      mortality and191 total major and minor complications. Pathological results were
      not analyzed in all studies and only 20 out of 41 provide data about the
      pathological results. Conclusion. Robotic surgery is safe and feasible option in
      colorectal surgery and a promising field; however, further prospective randomized
      studies are required to better define its role.

PMID- 22655206
TI  - Hepatocellular carcinoma: focus on different aspects of management.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third
      cause of cancer-related mortality worldwide. Its incidence is clearly arising
      comprised by the prevalence of major risk factors mainly hepatitis B and
      hepatitis C. The population at risk is composed of chronic liver patients at the
      stage of extensive fibrosis or cirrhosis. The monitoring programs of this
      population have allowed early detection of disease management to promote a
      radical therapy. Understanding the carcinogenic process and the mastery of the
      staging systems remain essential keys in diagnosis and treatment of HCC. Recent
      advances in diagnosis and new treatments have made important impacts on the
      disease by increasing survival rates and improving quality of life for HCC
      patients. This paper outlines the different management aspects of HCC which
      include epidemiology, prevention, carcinogenesis, staging systems, diagnosis,
      surveillance, and the treatment.

PMID- 22655208
TI  - A new surgical technique for ingrown toenail.
AB  - Background. Ingrowing toenails are a common condition which, when recurrent and
      painful, are often treated surgically. The aim of this study is to present a new
      simple surgical technique for ingrown toenails with good results. Method and
      Patients. The selected 250 patients with affected toes were surgically treated by
      our technique and observed from 1998 to 2004. Marginal nail elevation combined
      with surgical excision of the granulation tissue was more successful. For fixing
      the nail margin on the toe we have done one-bite suture by Nylon 3/0 that was
      removed after 3 weeks. Results. All patients were operated on by our new
      technique and the outcome was excellent; recurrence and failure of the technique
      were very low. Discussion. Because with this simple technique we excise the
      granulation tissue and elevate margin of nail over the skin, we will have higher
      cure rate, shorter postoperative pain, lower risk of postoperative infection, and
      remarkable cosmetic result without deformity; hence this technique should be
      considered as an alternative method of treatment.

PMID- 22655210
TI  - AMPA receptor trafficking in homeostatic synaptic plasticity: functional
      molecules and signaling cascades.
AB  - Homeostatic synaptic plasticity is a negative-feedback response employed to
      compensate for functional disturbances in the nervous system. Typically, synaptic
      activity is strengthened when neuronal firing is chronically suppressed or
      weakened when neuronal activity is chronically elevated. At both the whole cell
      and entire network levels, activity manipulation leads to a global up- or
      downscaling of the transmission efficacy of all synapses. However, the
      homeostatic response can also be induced locally at subcellular regions or
      individual synapses. Homeostatic synaptic scaling is expressed mainly via the
      regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
      (AMPAR) trafficking and synaptic expression. Here we review the recently
      identified functional molecules and signaling pathways that are involved in
      homeostatic plasticity, especially the homeostatic regulation of AMPAR
      localization at excitatory synapses.

PMID- 22655209
TI  - Synaptic functions of invertebrate varicosities: what molecular mechanisms lie
      beneath.
AB  - In mammalian brain, the cellular and molecular events occurring in both synapse
      formation and plasticity are difficult to study due to the large number of
      factors involved in these processes and because the contribution of each
      component is not well defined. Invertebrates, such as Drosophila, Aplysia, Helix,
      Lymnaea, and Helisoma, have proven to be useful models for studying synaptic
      assembly and elementary forms of learning. Simple nervous system, cellular
      accessibility, and genetic simplicity are some examples of the invertebrate
      advantages that allowed to improve our knowledge about evolutionary neuronal
      conserved mechanisms. In this paper, we present an overview of progresses that
      elucidates cellular and molecular mechanisms underlying synaptogenesis and
      synapse plasticity in invertebrate varicosities and their validation in
      vertebrates. In particular, the role of invertebrate synapsin in the formation of
      presynaptic terminals and the cell-to-cell interactions that induce specific
      structural and functional changes in their respective targets will be analyzed.

PMID- 22655211
TI  - Targeting the ACE2 and Apelin Pathways Are Novel Therapies for Heart Failure:
      Opportunities and Challenges.
AB  - Angiotensin-converting enzyme 2 (ACE2)/Ang II/Ang 1-7 and the apelin/APJ are two
      important peptide systems which exert diverse effects on the cardiovascular
      system. ACE2 is a key negative regulator of the renin-angiotensin system (RAS)
      where it metabolizes angiotensin (Ang) II into Ang 1-7, an endogenous antagonist
      of Ang II. Both the prolonged activation of RAS and the loss of ACE2 can be
      detrimental as they lead to functional deterioration of the heart and progression
      of cardiac, renal, and vascular diseases. Recombinant human ACE2 in an animal
      model of ACE2 knockout mice lowers Ang II. These interactions neutralize the
      pressor and subpressor pathologic effects of Ang II by producing Ang 1-7 levels
      in vivo, that might be cardiovascular protective. ACE2 hydrolyzes apelin to Ang
      II and, therefore, is responsible for the degradation of both peptides. Apelin
      has emerged as a promising peptide biomarker of heart failure. The serum level of
      apelin in cardiovascular diseases tends to be decreased. Apelin is recognized as
      an imperative controller of systemic blood pressure and myocardium contractility.
      Dysregulation of the apelin/APJ system may be involved in the predisposition to
      cardiovascular diseases, and enhancing apelin action may have important
      therapeutic effects.

PMID- 22655212
TI  - Microglia in Alzheimer brain: a neuropathological perspective.
AB  - Microglia have long been noted to be present and activated in Alzheimer brain.
      Demonstrations that these microglia are associated with the specific lesions of
      Alzheimer disease-Abeta plaques and neurofibrillary tangles-and that these
      microglia overexpress the potent proinflammatory cytokine interleukin-1 led to
      the recognition of a potential pathogenic role for these cells in initiation and
      progression of disease. Activated, cytokine-overexpressing microglia are near
      universal components of Abeta plaques at early (diffuse) and mid (neuritic)
      stages of progression in Alzheimer brain, and only decline in end-stage, dense
      core plaques. They correlate with plaque distribution across cerebral cortical
      cytoarchitectonic layers and across brain regions. They also show close
      associations with tangle-bearing neurons in Alzheimer brain. Microglial
      activation is a consistent feature in conditions that confer increased risk for
      Alzheimer disease or that are associated with accelerated appearance of Alzheimer
      type neuropathological changes. These include normal ageing, head injury,
      diabetes, heart disease, and chronic intractable epilepsy. The neuropathological
      demonstration of microglial activation in Alzheimer brain and in Alzheimer
      related conditions opened the field of basic and applied investigations centered
      on the idea of a pathogenically important neuroinflammatory process in Alzheimer
      disease.

PMID- 22655213
TI  - Alternative strategy for Alzheimer's disease: stress response triggers.
AB  - Stress resistance capacity is a hallmark of longevity protection and survival
      throughout the plant and animal kingdoms. Latent pathway activation of protective
      cascades, triggered by environmental challenges to tolerate heat, oxygen
      deprivation, reactive oxygen species (ROS), diet restriction, and exercise
      provides tolerance to these stresses. Age-related changes and disease
      vulnerability mark an increase in damage, like damage induced by environmental
      challenges. An alternative approach to immunotherapy intervention in Alzheimer's
      Disease is the use of mimetics of stress to upregulate endogenous protective
      cascades to repair age damage, shift the balance of apoptosis to regeneration to
      promote delay of onset, and even progression of Alzheimer's disease memory
      dysfunction. Mimetics of environmental stress, hormetic agents, and triggers,
      endogenous or engineered, can "trick" activation of expression patterns of repair
      and rejuvenation. Examples of known candidate triggers of heat response,
      endogenous antioxidants, DNA repair, exercise, hibernation, and telomeres are
      available for AD intervention trials. Telomeres and telomerase emerge as major
      regulators in crossroads of senescence, cancer, and rejuvenation responsive to
      mimetics of telomeres. Lessons emerge from transgenic rodent models, the long
      lived mole rat, clinical studies, and conserved innate pathways of stress
      resistance. Cross-reaction of benefits of different triggers promises
      intervention into seemingly otherwise unrelated diseases.

PMID- 22655215
TI  - Clarifying some fundamental errors in herries' "a chronological perspective on
      the acheulian and its transition to the middle stone age in southern Africa: the
      question of the fauresmith" (2011).
AB  - Herries provides a timely review of the archaeological and dating evidence of the
      transition from the Acheulean to the Middle Stone Age (MSA) in southern Africa,
      however, in relation to the site of Twin Rivers, Zambia he makes several
      fundamental errors of interpretation that demand correction. The stratigraphic
      sequence of the site is admittedly complex, but it deserves a more careful
      analysis than that offered by Herries. This detailed response by the most recent
      excavator of the site addresses Herries critique by placing the site in its
      historical context and then dealing with the central issue of the association of
      dated speleothem with the surviving archaeological deposits. Herries is shown to
      have mistakenly combined the dates from two separate cave passages and to have
      misunderstood the published sections, plans, and taphonomic assessment of each
      excavation area. His reinterpretation of the site as being significantly younger
      than published is based on a conflation of unrelated data.

PMID- 22655214
TI  - The biphasic role of microglia in Alzheimer's disease.
AB  - Neuroinflammation is involved in the pathogenesis of Alzheimer's disease (AD).
      Microglia, macrophage-like resident immune cells in the brain, play critical
      roles in the inflammatory aspects of AD. Microglia may be activated by oligomeric
      and fibrillar species of amyloid beta (Abeta) that are constituents of senile
      plaques and by molecules derived from degenerated neurons, such as purines and
      chemokines, which enhance their migration and phagocytosis. The main neurotoxic
      molecules produced by activated microglia may be reactive oxygen species,
      glutamate, and inflammatory cytokines such as tumor-necrosis-factor-alpha and
      interleukin- (IL-) 1beta These molecules differentially induce neurotoxicity.
      Abeta itself directly damages neurons. In terms of neuroprotective properties,
      microglia treated with fractalkine or IL-34 attenuate Abeta neurotoxicity by
      Abeta clearance and the production of antioxidants. Therefore, regulation of the
      microglial role in neuroprotection may be a useful therapeutic strategy for AD.

PMID- 22655216
TI  - Extensive Introgression among Ancestral mtDNA Lineages: Phylogenetic
      Relationships of the Utaka within the Lake Malawi Cichlid Flock.
AB  - We present a comprehensive phylogenetic analysis of the Utaka, an informal
      taxonomic group of cichlid species from Lake Malawi. We analyse both nuclear and
      mtDNA data from five Utaka species representing two (Copadichromis and Mchenga)
      of the three genera within Utaka. Within three of the five analysed species we
      find two very divergent mtDNA lineages. These lineages are widespread and occur
      sympatrically in conspecific individuals in different areas throughout the lake.
      In a broader taxonomic context including representatives of the main groups
      within the Lake Malawi cichlid fauna, we find that one of these lineages clusters
      within the non-Mbuna mtDNA clade, while the other forms a separate clade stemming
      from the base of the Malawian cichlid radiation. This second mtDNA lineage was
      only found in Utaka individuals, mostly within Copadichromis sp. "virginalis
      kajose" specimens. The nuclear genes analysed, on the other hand, did not show
      traces of divergence within each species. We suggest that the discrepancy between
      the mtDNA and the nuclear DNA signatures is best explained by a past
      hybridisation event by which the mtDNA of another species introgressed into the
      ancestral Copadichromis sp. "virginalis kajose" gene pool.

PMID- 22655217
TI  - Changes of TSH-Stimulation Blocking Antibody (TSBAb) and Thyroid Stimulating
      Antibody (TSAb) Over 10 Years in 34 TSBAb-Positive Patients with Hypothyroidism
      and in 98 TSAb-Positive Graves' Patients with Hyperthyroidism: Reevaluation of
      TSBAb and TSAb in TSH-Receptor-Antibody (TRAb)-Positive Patients.
AB  - TWO TRABS: TSBAb and TSAb. TSBAb causes hypothyroidism. TSAb causes Graves'
      hyperthyroidism. TSBAb and TSAb block TSH-binding to cells as TRAb, measured as
      TSH-binding inhibitory immunoglobulin (TBII). We reevaluate TSBAb and TSAb. We
      studied TSBAb, TSAb, and TBII over 10 years in 34 TSBAb-positives with
      hypothyroidism and in 98 TSAb-positives with hyperthyroidism. Half of the 34
      TSBAb-positives with hypothyroidism continued to have persistently positive
      TSBAb, continued to have hypothyroidism, and did not recover from hypothyroidism.
      Ten of the 98 TSAb-positives with hyperthyroidism continued to have positive TSAb
      and continued to have hyperthyroidism. TSBAb had disappeared in 15 of the 34
      TSBAb-positives with hypothyroidism. With the disappearance of TSBAb, recovery
      from hypothyroidism was noted in 13 (87%) of the 15 patients. TSAb had
      disappeared in 73 of the 98 TSAb-positives with hyperthyroidism. With the
      disappearance of TSAb, remissions of hyperthyroidism were noted in 60 (82%) of
      the 73. Two of the 34 TSBAb-positives with hypothyroidism developed TSAb-positive
      Graves' hyperthyroidism. Two of the 98 TSAb-positive Graves' patients with
      hyperthyroidism developed TSBAb-positive hypothyroidism. TSBAb and TSAb are
      TRAbs. TSBAb-hypothyroidism and TSAb-hyperthyroidism may be two aspects of one
      disease (TRAb disease). Two forms of autoimmune thyroiditis: atrophic and
      goitrous. We followed 34 TSBAb-positive patients with hypothyroidism (24 atrophic
      and 10 goitrous) over 10 years. All of the 10 TSBAb-positive goitrous patients
      recovered from hypothyroidism and 19 (79%) of the 24 TSBAb-positive atrophic
      patients continued to have hypothyroidism.

PMID- 22655219
TI  - Pathological and Immunological Developments in Behcet's Disease.

PMID- 22655218
TI  - Magnolol Protects against MPTP/MPP(+)-Induced Toxicity via Inhibition of
      Oxidative Stress in In Vivo and In Vitro Models of Parkinson's Disease.
AB  - The aim of this study is to investigate the role of magnolol in preventing 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-) induced neurodegeneration in
      mice and 1-methyl-4-phenylpyridinium ion-(MPP(+)-) induced cytotoxicity to human
      neuroblastoma SH-SY5Y cells and to examine the possible mechanisms. Magnolol (30
      mg/kg) was orally administered to C57BL/6N mice once a day for 4 or 5 days either
      before or after MPTP treatment. Western blot analysis revealed that MPTP
      injections substantially decreased protein levels of dopamine transporter (DAT)
      and tyrosine hydroxylase (TH) and increased glial fibrillary acidic protein
      (GFAP) levels in the striatum. Both treatments with magnolol significantly
      attenuated MPTP-induced decrease in DAT and TH protein levels in the striatum.
      However, these treatments did not affect MPTP-induced increase in GFAP levels.
      Moreover, oral administration of magnolol almost completely prevented MPTP
      induced lipid peroxidation in the striatum. In human neuroblastoma SH-SY5Y cells,
      magnolol significantly attenuated MPP(+)-induced cytotoxicity and the production
      of reactive oxygen species. These results suggest that magnolol has protective
      effects via an antioxidative mechanism in both in vivo and in vitro models of
      Parkinson's disease.

PMID- 22655220
TI  - Cytokeratin on frozen sections of sentinel node may spare breast cancer patients
      secondary axillary surgery.
AB  - Background. The feasibility and accuracy of immunohistochemistry (IHC) on frozen
      sections, when assessing sentinel node (SN) status intraoperatively in breast
      cancer, is a matter of continuing discussion. In this study, we compared a center
      using IHC on frozen section with a center not using this method with focus on
      intraoperative diagnostic values. Material and Methods. Results from 336 patients
      from the centre using IHC intraoperatively were compared with 343 patients from
      the center not using IHC on frozen section. Final evaluation on paraffin sections
      with haematoxylin-eosin (HE) staining supplemented with cytokeratin staining was
      used as gold standard. Results. Significantly more SN with isolated tumor cells
      (ITCs) and micrometastases (MICs) were found intraoperatively when using IHC on
      frozen sections. There was no significant difference in the number of
      macrometastases (MACs) found intraoperatively. IHC increased the sensitivity, the
      negative predictive value, and the accuracy of the intraoperative evaluation of
      SN without decreasing the specificity and positive predictive value of SN
      evaluation. Conclusions. IHC on frozen section leads to the detection of more ITC
      and MIC intraoperatively. As axillary lymph node dissection (ALND) is performed
      routinely in some countries when ITC and MIC are found in the SN, IHC on frozen
      section provides valuable information that can lead to fewer secondary ALNDs.

PMID- 22655221
TI  - Total hip arthroplasty in developmental dysplasia of the hip: Review of anatomy,
      techniques and outcomes.
AB  - Total hip arthroplasty (THA) in developmental dysplasia of the hip (DDH) presents
      many challenges to the reconstructive surgeon. The complex femoral and acetabular
      anatomy makes standard reconstruction technically challenging. Acetabular
      coverage can be improved by medialization of the component or augmentation of the
      deficient areas with bone graft. Femoral shortening osteotomies are considered in
      cases of severe dysplasia and frankly dislocated hips. Each patient's unique
      anatomy dictates what options of reconstruction are available. The functional
      outcomes of THA in DDH are generally excellent, though higher rates of mechanical
      failure have been reported in this group. This article reviews the anatomy,
      classification, technical considerations, and outcomes of THA in patients with
      DDH.

PMID- 22655222
TI  - Osteonecrosis of the femoral head: An update in year 2012.
AB  - Osteonecrosis is a phenomenon involving disruption to the vascular supply to the
      femoral head, resulting in articular surface collapse and eventual
      osteoarthritis. Although alcoholism, steroid use, and hip trauma remain the most
      common causes, several other etiologies for osteonecrosis have been identified.
      Basic science research utilizing animal models and stem cell applications
      continue to further elucidate the pathophysiology of osteonecrosis and promise
      novel treatment options in the future. Clinical studies evaluating modern joint
      sparing procedures have demonstrated significant improvements in outcomes, but
      hip arthroplasty is still the most common procedure performed in these affected
      younger adults. Further advances in joint-preserving procedures are required and
      will be widely studied in the coming decade.

PMID- 22655223
TI  - Scurvy: An unusual presentation of cerebral palsy.
AB  - Scurvy is caused by prolonged severe dietary deficiency of ascorbic acid, in
      which the breakdown of intercellular cement substances leads to capillary
      hemorrhages and defective growth of fibroblasts, osteoblasts and odontoblasts,
      resulting in impaired synthesis of collagen, osteoid and dentine. It is
      characterized by hemorrhagic gingivitis, subperiosteal hemorrhages,
      perifollicular hemorrhages, and frequently petechial hemorrhages (especially on
      the feet). People with abnormal dietary habits, mental illness or physical
      disability are prone to develop this disease. Epiphyseal separation is known to
      occur in scurvy but is rarely seen now. Epiphyseal separation from the metaphysis
      is always through the zone of calcified cartilage, known as "scorbutic lattice",
      which in the radiographs is represented as "the white line of Frenkel". We report
      a case of multiple epiphyseal separations in a cerebral palsy child because of
      vitamin C deficiency. The child was treated with splintage of extremity and
      nutritional supplementation. All physeal separation healed completely without any
      deformity.

PMID- 22655225
TI  - The grand challenges to cellular and molecular oncology.

PMID- 22655224
TI  - Past, present, and future of molecular and cellular oncology.
AB  - In the last 20 years, the field of cellular and molecular oncology has been born
      and has moved its first steps, with an increasingly rapid pace. Hundreds of
      oncogenic and oncosuppressive signaling cascades have been characterized,
      facilitating the development of an ever more refined and variegated arsenal of
      diagnostic and therapeutic weapons. Furthermore, several cancer-specific features
      and processes have been identified that constitute promising therapeutic targets.
      For instance, it has been demonstrated that microRNAs can play a critical role in
      oncogenesis and tumor suppression. Moreover, it turned out that tumor cells
      frequently exhibit an extensive metabolic rewiring, can behave in a stem cell
      like fashion (and hence sustain tumor growth), often constitutively activate
      stress response pathways that allow them to survive, can react to therapy by
      engaging in non-apoptotic cell death programs, and sometimes die while eliciting
      a tumor-specific immune response. In this Perspective article, we discuss the
      main issues generated by these discoveries that will be in the limelight of
      molecular and cellular oncology research for the next, hopefully few years.

PMID- 22655226
TI  - Challenges in cancer molecular targets and therapeutics.

PMID- 22655228
TI  - A rapid, simple DNA mismatch repair substrate construction method.
AB  - A more flexible and higher-yielding in vitro DNA mismatch repair (MMR) substrate
      construction method, which was developed initially by Wang and Hays, is described
      for the construction of a nucleotide-based chemical mismatch (G/IU) and a G/T
      mismatch. Our modifications use the combination of two endonuclease enzymes (NheI
      and BciVI) and two new redesigned plasmids (pWDAH1A and pWDSH1B). In our modified
      methodology, plasmids are initially digested with the nicking endonucleases,
      followed by the streptavidin treatment. The mismatch-containing oligo is then
      annealed to the gap DNA and finally ligated to produce a mismatch-containing DNA
      substrate. We report a high efficiency (up to 90%) of these mismatch substrates
      and confirm recognition using a functional assay. These modifications, coupled
      with the use of the redesigned plasmids, can be applied for the construction of
      other types of chemically induced mismatches as well as insertion-deletion loops
      for future in vitro studies of MMR processing by our group and others.

PMID- 22655229
TI  - Using baldrige performance excellence program approaches in the pursuit of
      radiation oncology quality care, patient satisfaction, and workforce commitment.
AB  - The Malcolm Baldrige National Quality Improvement Act was signed into law in 1987
      to advance US business competitiveness and economic growth. Administered by the
      National Institute of Standards and Technology, the Act created the Baldrige
      National Quality Program, recently renamed the Baldrige Performance Excellence
      Program. The comprehensive analytical approaches referred to as the Baldrige
      Healthcare Criteria, are very well-suited for the evaluation and sustainable
      improvement of radiation oncology management and operations. A multidisciplinary
      self-assessment approach is used for radiotherapy program evaluation and
      development in order to generate a fact-based, knowledge-driven system for
      improving quality of care, increasing patient satisfaction, enhancing leadership
      effectiveness, building employee engagement, and boosting organizational
      innovation. This methodology also provides a valuable framework for benchmarking
      an individual radiation oncology practice's operations and results against
      guidelines defined by accreditation and professional organizations and regulatory
      agencies.

PMID- 22655227
TI  - Cell death signaling and anticancer therapy.
AB  - For a long time, it was commonly believed that efficient anticancer regimens
      would either trigger the apoptotic demise of tumor cells or induce a permanent
      arrest in the G(1) phase of the cell cycle, i.e., senescence. The recent
      discovery that necrosis can occur in a regulated fashion and the increasingly
      more precise characterization of the underlying molecular mechanisms have raised
      great interest, as non-apoptotic pathways might be instrumental to circumvent the
      resistance of cancer cells to conventional, pro-apoptotic therapeutic regimens.
      Moreover, it has been shown that some anticancer regimens engage lethal signaling
      cascades that can ignite multiple oncosuppressive mechanisms, including
      apoptosis, necrosis, and senescence. Among these signaling pathways is mitotic
      catastrophe, whose role as a bona fide cell death mechanism has recently been
      reconsidered. Thus, anticancer regimens get ever more sophisticated, and often
      distinct strategies are combined to maximize efficacy and minimize side effects.
      In this review, we will discuss the importance of apoptosis, necrosis, and
      mitotic catastrophe in the response of tumor cells to the most common clinically
      employed and experimental anticancer agents.

PMID- 22655230
TI  - Therapeutic targeting of cancer stem cells.
AB  - Recent breakthroughs in translational oncology are opening new perspectives for
      the treatment of cancer. The advent of targeted therapies has provided the proof
      of-concept to selectively turn-off deregulated oncogenic proteins, while the
      identification and validation of predictive biomarkers of response has allowed to
      improve, at least in some cases, their performance. Moreover, a subpopulation of
      tumor-propagating cells has been identified from many solid and hematological
      tumors. These cells share functional properties of normal stem cells, and are
      commonly referred to as cancer stem cells (CSCs). It is emerging that CSCs are
      defended against broadly used anticancer agents by means of different, partly
      interconnected, mechanisms. However, CSCs rely on specific pathways involved in
      self-renewal that can be pharmacologically antagonized by experimental molecular
      targeted agents, some of which have recently entered early phases of clinical
      development. Here, we discuss the spectrum of pharmacological strategies under
      clinical or preclinical development for CSCs targeting.

PMID- 22655231
TI  - Sequence Variants and the Risk of Head and Neck Cancer: Pooled Analysis in the
      INHANCE Consortium.
AB  - Previous molecular epidemiological studies on head and neck cancer have examined
      various single nucleotide polymorphisms (SNPs), but there are very few documented
      associations. In the International head and neck cancer epidemiology (INHANCE)
      consortium, we evaluated associations between SNPs in the metabolism, cell cycle,
      and DNA repair pathways and the risk of head and neck cancer. We analyzed
      individual-level pooled data from 14 European, North American, Central American,
      and Asia case-control studies (5,915 head and neck cancer cases and 10,644
      controls) participating in the INHANCE consortium. Unconditional logistic
      regression was used to estimate odds ratios (OR) and 95% confidence intervals
      (CI) for SNP effects, adjusting for age, sex, race, and country. We observed an
      association between head and neck cancer risk and MGMT Leu84Phe heterozygotes (OR
      = 0.79, 95% CI = 0.68-0.93), XRCC1 Arg194Trp homozygotes Arg/Arg (OR = 2.3, 95%
      CI = 1.1-4.7), ADH1B Arg48His homozygotes Arg/Arg (OR = 2.7, 95% CI = 1.9-4.0),
      ADH1C Ile350Val homozygotes Ile/Ile (OR = 1.2, 95% CI = 1.1-1.4), and the GSTM1
      null genotype (OR = 1.1, 95% CI = 1.0-1.2). Among these results, MGMT Leu84Phe,
      ADH1B Arg48His, ADH1C Ile350Arg, and the GSTM1 null genotype had fairly low false
      positive report probabilities (<20%). We observed associations between ADH1B
      Arg48His, ADH1C Ile350Arg, and GSTM1 null genotype and head and neck cancer risk.
      No functional study currently supports the observed association for MGMT
      Leu84Phe, and the association with XRCC1 Arg194Trp may be a chance finding.

PMID- 22655232
TI  - Mesenchymal stem cell therapy in the treatment of acute and chronic graft versus
      host disease.
AB  - Mesenchymal stem cells (MSC) are a cellular component of the supportive
      microenvironment (stroma) found in the bone marrow, umbilical cord, placenta, and
      adipose tissues. In addition to providing cellular and extracellular cues to
      support the proliferation and differentiation of cells that comprise functional
      tissues, MSC also contribute to tissue repair and have immunomodulatory
      properties. Their ability to modulate immunologic reactions while themselves not
      provoking immunologic responses from alloreactive T-lymphocytes and/or other
      effector cells, make MSC a potentially ideal therapeutic agent with which to
      treat graft versus host disease (GvHD) following hematopoietic transplantation.
      Despite in vitro experiments confirming that MSC suppress mixed lymphocyte
      reactions (MLR) and in vivo evidence from mouse models that show evidence that
      MSC can ameliorate GvHD, clinical trials to date using MSC to treat GvHD have
      shown mixed results. Whether this is a consequence of suboptimal timing and dose
      of administered MSC remains to be clarified. It is clear that immunomodulatory
      potential of MSC as a cellular therapy for GvHD remains to be realized in the
      clinic.

PMID- 22655233
TI  - In search of targeted therapies for childhood cancer.

PMID- 22655234
TI  - Targeting apoptosis signaling pathways for anticancer therapy.
AB  - Treatment approaches for cancer, for example chemotherapy, radiotherapy, or
      immunotherapy, primarily act by inducing cell death in cancer cells.
      Consequently, the inability to trigger cell death pathways or alternatively,
      evasion of cancer cells to the induction of cell death pathways can result in
      resistance of cancers to current treatment protocols. Therefore, in order to
      overcome treatment resistance a better understanding of the underlying mechanisms
      that regulate cell death and survival pathways in cancers and in response to
      cancer therapy is necessary to develop molecular-targeted therapies. This
      strategy should lead to more effective and individualized treatment strategies
      that selectively target deregulated signaling pathways in a tumor type- and
      patient-specific manner.

PMID- 22655235
TI  - Proton Therapy: Ever Shifting Sands and the Opportunities and Obligations within.
AB  - Proton therapy is associated with significant benefit in terms of normal tissue
      sparing and potential radiation dose escalation for many patients with malignant
      diseases. Due to recognition of these qualities, the availability of this
      technology is increasing rapidly, both through increased availability of large
      centers, and with the possibility of smaller, lower cost proton therapy centers.
      Such expansion is associated with increased opportunity to provide this
      beneficial technology to larger numbers of patients; however, the importance of
      careful treatment planning and delivery, deliberate patient selection, rigorous
      scientific investigation including comparison to other technologies when
      possible, and mindfulness of ethical issues and cost effectiveness must not be
      forgotten. The obligation to move forward responsibly rests on the shoulders of
      radiation oncologists around the world. In this article, we discuss current use
      of proton therapy worldwide, as well as many of the factors that must be taken
      into account during rapid expansion of this exciting technology.

PMID- 22655237
TI  - Effects of a fluorescent Myosin light chain phosphatase inhibitor on prostate
      cancer cells.
AB  - Myosin light chain phosphatase (MLCP) is an enzyme important to regulation of
      cell cycle and motility that is shown to be upregulated in aggressive prostate
      cancer cells and tissue. We developed a fluorescent small molecule inhibitor of
      MLCP using structure based design in recombinant protein phosphatase 1C. Several
      best fit compounds were synthesized and evaluated by their inhibition of
      MLCP/(32)P-MLC dephosphorylation, which resulted in the identification of novel
      MLCP inhibitors. Androgen dependent (AD) and castration resistant prostate cancer
      cell (CRPC) lines were treated with the lead inhibitor resulting in decreased
      growth rate, reduced DNA synthesis, and G2/M cell cycle arrest. Moreover, CRPC
      cell lines showed an increased sensitivity to drug treatment having GI(50) values
      four times lower than the AD prostate cancer cell line. This was reinforced by
      reduced BrdU DNA incorporation into CRPC cells compared to AD cells. beta-actin
      disruption was also seen at much lower drug concentrations in CR cells which
      caused a dose dependent reduction in cellular chemotaxis of PC-3 cells. Since
      there are currently few clinical therapeutics targeting CR prostate cancer, MLCP
      represents a new target for preclinical and clinical development of new potential
      therapeutics which inhibit this disease phenotype.

PMID- 22655236
TI  - Protease addiction and synthetic lethality in cancer.
AB  - The "oncogene addiction" concept refers to the dependence of cancer cells on the
      function of the oncogenes responsible for their transformed phenotype, while the
      term "non-oncogene addiction" has been introduced to define the exacerbated
      necessity of the normal function of non-mutated genes. In this Perspective, we
      focus on the importance of proteolytic enzymes to maintain the viability of
      cancer cells and hypothesize that most, if not all, tumors present "addiction" to
      a number of proteolytic activities, which in turn may represent valuable targets
      of anti-cancer therapies, even without being mutated or over-expressed by the
      malignant cells.

PMID- 22655238
TI  - An optically pure apogossypolone derivative as potent pan-active inhibitor of
      anti-apoptotic bcl-2 family proteins.
AB  - Our focus in the past several years has been on the identification of novel and
      effective pan-Bcl-2 antagonists. We have recently reported a series of
      Apogossypolone (ApoG2) derivatives, resulting in the chiral compound (+/-)
      BI97D6. We report here the synthesis and evaluation on its optically pure (-) and
      (+) atropisomers. Compound (-) BI97D6 potently inhibits the binding of BH3
      peptides to Bcl-X(L), Bcl-2, Mcl-1, and Bfl-1 with IC(50) values of 76 +/- 5, 31
      +/- 2, 25 +/- 8, and 122 +/- 28 nM, respectively. In a cellular assay, compound (
      ) BI97D6 effectively inhibits cell growth in the PC-3 human prostate cancer and
      H23 human lung cancer cell lines with EC(50) values of 0.22 +/- 0.08 and 0.14 +/-
      0.02 MUM, respectively. Similarly, compound (-) BI97D6 effectively induces
      apoptosis in the BP3 human lymphoma cell line in a dose-dependent manner. The
      compound also shows little cytotoxicity against bax(-/-)/bak(-/-) cells,
      suggesting that it kills cancers cells predominantly via a Bcl-2 pathway.
      Moreover, compound (-) BI97D6 displays in vivo efficacy in both a Bcl-2
      transgenic mouse model and in a prostate cancer xenograft model in mice.
      Therefore, compound (-) BI97D6 represents a promising drug lead for the
      development of novel apoptosis-based therapies for cancer.

PMID- 22655239
TI  - Impact of Autophagy on Chemotherapy and Radiotherapy Mediated Tumor Cytotoxicity:
      "To Live or not to Live".
AB  - Autophagy, a highly regulated cell "self-eating" pathway, is controlled by the
      action of over 34 autophagy-related proteins (collectively termed Atgs). Although
      they are fundamentally different processes, autophagy and apoptosis (type I
      programmed cell death), under certain circumstances, can be regulated by common
      signaling mediators. Current cancer therapies including chemotherapy and ionizing
      radiation are known to induce autophagy within tumor cells. However, autophagy
      plays a dual role of either pro-cell survival or pro-cell death in response to
      these cancer treatments, depending on the cellular context and the nature of the
      treatment. We review the current basic and translational cancer research
      literature on how autophagy impacts tumor cell survival ("to live") and death
      ("not to live") following treatment as well as the role of chemical mediators of
      autophagy.

PMID- 22655240
TI  - The role of a prone setup in breast radiation therapy.
AB  - Most patients undergoing breast conservation therapy receive radiotherapy in the
      supine position. Historically, prone breast irradiation has been advocated for
      women with large pendulous breasts in order to decrease acute and late
      toxicities. With the advent of CT planning, the prone technique has become both
      feasible and reproducible. It was shown to be advantageous not only for women
      with larger breasts but in most patients since it consistently reduces, if not
      eliminates, the inclusion of heart and lung within the field. The prone setup has
      been accepted as the best localizing position for both MRI and stereotactic
      biopsy, but its adoption has been delayed in radiotherapy. New technological
      advances including image-modulated radiation therapy and image-guided radiation
      therapy have made possible the exploration of accelerated fractionation schemes
      with a concomitant boost to the tumor bed in the prone position, along with
      better imaging and verification of reproducibility of patient setup. This review
      describes some of the available techniques for prone breast radiotherapy and the
      available experience in their application. The NYU prone breast radiotherapy
      approach is discussed, including a summary of the results from several
      prospective trials.

PMID- 22655241
TI  - Development of real-time quantitative polymerase chain reaction assays to track
      treatment response in retinoid resistant acute promyelocytic leukemia.
AB  - Molecular detection of minimal residual disease (MRD) has become established to
      assess remission status and guide therapy in patients with ProMyelocytic Leukemia
      RARA+ acute promyelocytic leukemia (APL). However, there are few data on tracking
      disease response in patients with rarer retinoid resistant subtypes of APL,
      characterized by PLZF-RARA and STAT5b-RARA. Despite their rarity (<1% of APL) we
      identified 6 cases (PLZF-RARA, n = 5; STAT5b-RARA, n = 1), established the
      respective breakpoint junction regions and designed reverse transcription
      quantitative real-time polymerase chain reaction (RT-qPCR) assays to detect
      leukemic transcripts. The relative level of fusion gene expression in diagnostic
      samples was comparable to that observed in t(15;17) - associated APL, affording
      assay sensitivities of ~1 in 10(4)-10(5). Serial samples were available from two
      PLZF-RARA APL patients. One showed persistent polymerase chain reaction
      positivity, predicting subsequent relapse, and remains in CR2, ~11 years post
      autograft. The other, achieved molecular remission (CRm) with combination
      chemotherapy, remaining in CR1 at 6 years. The STAT5b-RARA patient failed to
      achieve CRm following frontline combination chemotherapy and ultimately proceeded
      to allogeneic transplant on the basis of a steadily rising fusion transcript
      level. These data highlight the potential of RT-qPCR detection of MRD to
      facilitate development of more individualized approaches to the management of
      rarer molecularly defined subsets of acute leukemia.

PMID- 22655242
TI  - Combined modality approaches in the management of adult glioblastoma.
AB  - Over the past two decades, management of newly diagnosed glioblastoma has
      undergone significant evolution. While surgery has long been a mainstay of
      management for this disease, and while radiotherapy has a proven survival role,
      initial efforts at radiotherapy dose escalation, use of radiosurgery,
      brachytherapy, and altered fractionation did not improve patient survival.
      Recently, multiple modality therapy integrating maximal safe resection,
      postoperative radiation, and new systemic therapies have resulted in improved
      patient outcomes compared with older regimens utilizing surgery and postoperative
      radiation alone. Numerous trials are currently underway investigating the
      combination of surgery, radiation, and systemic therapy with targeted agents to
      find ways to further improve outcomes for adults with glioblastoma.

PMID- 22655243
TI  - Multiple Human Papillomavirus Infections among Chinese Women with and without
      Cervical Abnormalities: A Population-Based Multi-Center Cross-Sectional Study.
AB  - BACKGROUND: Despite an increase in the number of studies conducted in recent
      years on human papillomavirus (HPV) and cervical cancer epidemiology, the profile
      of multiple HPV infections remain obscure, particularly among Chinese women.
      During 2004-2005, a series of population-based HPV prevalence surveys were
      performed by Cancer Institute and Hospital of Chinese Academy of Medical Sciences
      (CIHCAMS) and International Agency for Research on Cancer (IARC). Based on these
      surveys, we evaluated the prevalence and risk factors of multiple HPV infections,
      and explored its association with cervical abnormalities among Chinese women.
      METHODS: A total of 2374 women from three study centers underwent gynecological
      examinations with valid cytology and their HPV results were included in the
      analysis. Forty-four HPV types were detected using the GP5+/6+ PCR-based enzyme
      immunoassay. An unconditional logistic regression model was used to evaluate the
      effect of multiple HPV infections on cervical lesions and its risk factors
      adjusting for confounders. The between-groups difference was evaluated by a
      heterogeneity test based on the Q test. RESULTS: One hundred and eleven women of
      multiple HPV infections was found among 2374 Chinese women with a prevalence of
      5.28% (95% CI = 3.86-5.60%), which attributed to 28.98% (95% CI = 24.49-33.81%)
      of all of the 383 HPV-positive women. A significantly increased risk of multiple
      HPV infections was found in the older women (>=45 years; adjusted OR = 1.52, 95%
      CI = 1.02-2.27) and those having more than three sexual partners (adjusted OR =
      2.10, 95% CI = 1.05-4.17) after adjustment for age-group, study area, and number
      of sexual partner. We also found that the risk of high-grade lesions was
      significantly higher than that of low-grade lesions with the multiple HPV
      infections (P(heterogeneity) = 0.044), but not as significantly with the single
      HPV infection (P(heterogeneity) = 0.108). CONCLUSION: Multiple HPV Infections,
      especially with high-risk HPV types, may be a substantial indicator either for
      public cervical cancer prevention or clinical implications.

PMID- 22655245
TI  - Influence of pH on the Cytotoxic Activity of Inositol Hexakisphosphate (IP6) in
      Prostate Cancer.
AB  - OBJECTIVES: In the present study, we investigated whether the pH of IP6 could
      influence its anti-tumoral activity in vitro. METHODS: PC-3 cells were exposed to
      IP6 at pH 5, pH 7, and pH 12 and we evaluated the metabolic activity (WST-1
      assay), cell proliferation (cell count), cell cycle distribution (FACS), and
      mitochondrial depolarization (JC-1 staining) in vitro. RESULTS: Our results
      demonstrated that IP6 at pH 5 and pH 12 were more potent at lowering the
      metabolic activity of PC-3 cells than IP6 at pH 7. Treatment with IP6 at pH 12
      also caused the greatest inhibition in cellular proliferation and accumulation of
      PC-3 cells in sub-G1. Finally, IP6 at pH 12 lead to a reduction in phospho-AKT
      and phospho-PDK1 and upregulated phospho-ERK. CONCLUSION: Together, our data
      strongly suggest that the pH of IP6 effectively modulates its anti-tumoral
      activity and should be reported in future studies.

PMID- 22655246
TI  - FDG Dose Extravasations in PET/CT: Frequency and Impact on SUV Measurements.
AB  - OBJECTIVES: Positron emission tomography (PET)/CT with 18F-FDG has proven to be
      effective in detecting and assessing various types of cancers. However, due to
      cancer and/or its therapy, intravenous (IV) FDG injection may be problematic
      resulting in dose extravasations. In the most frequently used field of view
      (FOV), arms-up, and base of skull to upper thigh [limited whole body (LWB)], the
      injection site may not be routinely imaged. The purpose of this study was to
      evaluate the frequency of dose extravasations in FDG PET and the potential impact
      on standard uptake value (SUV) measurements. METHODS: True whole body FDG PET/CT
      scans (including all extremities) of 400 patients were retrospectively reviewed.
      A log recorded cases of IV dose extravasations. When possible, SUVs were measured
      in two frequently used reference locations: mediastinum and liver. The SUVs were
      obtained in the same patients who had studies with and without FDG extravasations
      within an average of 3 months without interval therapy. RESULTS: Of the 400
      scans, 42 (10.5%) had extravasations on the maximum intensity projections images.
      In scans with or without dose infiltration, FDG injection site was at or distal
      to the antecubital fossa in 97% of studies. Of those 42 cases, dose infiltration
      was within the LWB FOV in 29/42 (69%) and outside in the remaining 13/42 (31%).
      Of those 42 patients, 5 had repeat PET studies with no interval therapy. For
      those 5 patients, liver maximum SUV was 11.7% less in patients with infiltration
      than those without (2.22 +/- 0.54 vs. 2.48 +/- 0.6). Mediastinum SUVmax was 9.3%
      less in patients with infiltration than those without (1.72 +/- 0.54 vs. 1.88 +/-
      0.49). CONCLUSION: We conclude dose extravasations were commonly encountered
      (10.5%) in PET/CT. However, it is underreported by at least 31% due to omitting
      injection site from the FOV. When present, extravasations may lead to
      underestimation of SUVmax. Therefore, it should not only be avoided but also
      reported in order to avoid false interpretations of the exam.

PMID- 22655247
TI  - Adjuvant chemotherapy for early stage non-small cell lung cancer.
AB  - For many years adjuvant chemotherapy has been a standard treatment after complete
      resection in malignancies such as breast and colon but only recently has its use
      become standard in early stage non-small cell lung cancer (NSCLC). Although
      surgery is regarded as the best possible treatment for early stage NSCLC, only 20
      25% of patients have resectable disease at presentation. Despite optimal surgical
      treatment, 5-year survival rates for NSCLC remain 50-60% for stage IB, 40-50% for
      stage II, and 20-30% for stage III (Kohler et al., 2011; Siegel et al., 2011).
      Adjuvant chemotherapy provides additional survival benefit in resected NSCLC but
      questions remain as to how to select patients for therapy and which regimen is
      best. Other than work with tegafur/uracil in Japan, the positive adjuvant trials
      have all utilized a cisplatin backbone, but the drug(s) to pair with cisplatin
      are a matter of debate and will be discussed further in this manuscript.

PMID- 22655244
TI  - Glutathione s-transferases in pediatric cancer.
AB  - The glutathione S-transferases (GSTs) are a family of ubiquitously expressed
      polymorphic enzymes important for detoxifying endogenous and exogenous compounds.
      In addition to their classic activity of detoxification by conjugation of
      compounds with glutathione, many other functions are now found to be associated
      with GSTs. The associations between GST polymorphisms/functions and human disease
      susceptibility or treatment outcome, mostly in adults, have been extensively
      studied and reviewed. This mini review focuses on studies related to GST
      epidemiology and functions related to pediatric cancer. Opportunities to exploit
      GST in pediatric cancer therapy are also discussed.

PMID- 22655248
TI  - Six-Dimensional Correction of Intra-Fractional Prostate Motion with CyberKnife
      Stereotactic Body Radiation Therapy.
AB  - Large fraction radiation therapy offers a shorter course of treatment and
      radiobiological advantages for prostate cancer treatment. The CyberKnife is an
      attractive technology for delivering large fraction doses based on the ability to
      deliver highly conformal radiation therapy to moving targets. In addition to
      intra-fractional translational motion (left-right, superior-inferior, and
      anterior-posterior), prostate rotation (pitch, roll, and yaw) can increase
      geographical miss risk. We describe our experience with six-dimensional (6D)
      intra-fraction prostate motion correction using CyberKnife stereotactic body
      radiation therapy (SBRT). Eighty-eight patients were treated by SBRT alone or
      with supplemental external radiation therapy. Trans-perineal placement of four
      gold fiducials within the prostate accommodated X-ray guided prostate
      localization and beam adjustment. Fiducial separation and non-overlapping
      positioning permitted the orthogonal imaging required for 6D tracking. Fiducial
      placement accuracy was assessed using the CyberKnife fiducial extraction
      algorithm. Acute toxicities were assessed using Common Toxicity Criteria v3.
      There were no Grade 3, or higher, complications and acute morbidity was minimal.
      Ninety-eight percent of patients completed treatment employing 6D prostate motion
      tracking with intra-fractional beam correction. Suboptimal fiducial placement
      limited treatment to 3D tracking in two patients. Our experience may guide others
      in performing 6D correction of prostate motion with CyberKnife SBRT.

PMID- 22655249
TI  - Stereotactic Body Radiation Therapy for Low- and Low-Intermediate-Risk Prostate
      Cancer: Is there a Dose Effect?
AB  - This study examines the efficacy and toxicity of two stereotactic body radiation
      therapy (SBRT) dose regimens for treatment of early prostate cancer. Forty-one
      patients treated with 35 Gy were matched with 41 patients treated with 36.25 Gy.
      Both patient groups received SBRT in five fractions over five consecutive days
      using the CyberKnife. Each group had 37 low-risk patients and 4 intermediate-risk
      patients. No statistically significant differences were present for age, prostate
      volume, PSA, Gleason score, stage, or risk between the groups. The dose was
      prescribed to the 83-87% isodose line to cover the prostate and a 5-mm margin all
      around, except 3 mm posteriorly. The overall median follow-up is 51 months
      (range, 45-58 months) with a median 54 and 48 months follow-up for the 35 and
      36.25-Gy dose groups, respectively. One biochemical failure occurred in each
      group yielding a 97.5% freedom from biochemical failure. The PSA response has
      been favorable for all patients with a mean PSA of 0.1 ng/ml at 4-years. Overall
      toxicity has been mild with 5% late grade 2 rectal toxicity in both dose groups.
      Late grade 1 urinary toxicity was equivalent between groups; grade 2 urinary
      toxicity was 5% (2/41 patients) and 10% (4/41 patients) in the 35-Gy and 36.25-Gy
      dose groups (p = 0.6969), respectively. Overall, the highly favorable PSA
      response, limited biochemical failures, limited toxicity, and limited impact on
      quality of life in these low- to low-intermediate-risk patients are supportive of
      excellent long-term results for CyberKnife delivered SBRT.

PMID- 22655250
TI  - Renal cell cancer: what can we learn from pre-operative studies?

PMID- 22655251
TI  - PI3K Pathway in NSCLC.
AB  - The phosphatidylinositol 3-kinases (PI3Ks) are members of a family of
      intracellular lipid kinases that phosphorylate the 3'-hydroxyl group of
      phosphatidylinositol and phosphoinositides. PI3K regulate signaling pathways for
      neoplasia, including cell proliferation, adhesion, survival, and motility.
      Different classes of PI3K have distinct roles in cellular signal transduction.
      PI3K pathway is activated by several different mechanisms in cancers, including,
      somatic mutation and gene amplification. In this review, we examine the
      literature addressing PI3K mutation status and gene amplification, with an
      emphasis on non-small cell lung cancer.

PMID- 22655252
TI  - Ribonucleotide reductase inhibitors: a new look at an old target for
      radiosensitization.
AB  - Ribonucleotide reductase (RR), the rate limiting enzyme in the synthesis and
      repair of DNA, has been studied as a target for inhibition in the treatment of
      cancer for many years. While some researchers have focused on RR inhibitors as
      chemotherapeutic agents, particularly in hematologic malignancies, some of the
      most promising data has been generated in the field of radiosensitization. Early
      pre-clinical studies demonstrated that the addition of the first of these drugs,
      hydroxyurea, to ionizing radiation (IR) produced a synergistic effect in vitro,
      leading to a large number of clinical studies in the 1970-1980s. These studies,
      mainly in cervical cancer, initially produced a great deal of interest, leading
      to the incorporation of hydroxyurea in the treatment protocols of many
      institutions. However, over time, the conclusions from these studies have been
      called into question and hydroxyurea has been replaced in the standard of care of
      cervical cancer. Over the last 10 years, a number of well-done pre-clinical
      studies have greatly advanced our understanding of RR as a target. Those advances
      include the elucidation of the role of p53R2 and our understanding of the
      temporal relationship between the delivery of IR and the response of RR. At the
      same time, new inhibitors with increased potency and improved binding
      characteristics have been discovered, and pre-clinical and early clinical data
      look promising. Here we present a comprehensive review of the pre-clinical and
      clinical data in the field to date and provide some discussion of future areas of
      research.

PMID- 22655253
TI  - Pheochromocytoma and paraganglioma: current functional and future molecular
      imaging.
AB  - Paragangliomas are neural crest-derived tumors, arising either from chromaffin
      sympathetic tissue (in adrenal, abdominal, intra-pelvic, or thoracic paraganglia)
      or from parasympathetic tissue (in head and neck paraganglia). They have a
      specific cellular metabolism, with the ability to synthesize, store, and secrete
      catecholamines (although most head and neck paragangliomas do not secrete any
      catecholamines). This disease is rare and also very heterogeneous, with various
      presentations (e.g., in regards to localization, multifocality, potential to
      metastasize, biochemical phenotype, and genetic background). With growing
      knowledge, notably about the pathophysiology and genetic background, guidelines
      are evolving rapidly. In this context, functional imaging is a challenge for the
      management of paragangliomas. Nuclear imaging has been used for exploring
      paragangliomas for the last three decades, with MIBG historically as the first
      line exam. Tracers used in paragangliomas can be grouped in three different
      categories. Agents that specifically target catecholamine synthesis, storage, and
      secretion pathways include: 123 and 131I-metaiodobenzylguanidine (123/131I-MIBG),
      18F-fluorodopamine (18F-FDA), and 18F-fluorodihydroxyphenylalanine (18F-FDOPA).
      Agents that bind somatostatin receptors include 111In-pentetreotide and 68Ga
      labeled somatostatin analog peptides (68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA
      TATE). The non-specific agent most commonly used in paragangliomas is 18F
      fluorodeoxyglucose (18F-FDG). This review will first describe conventional
      scintigraphic exams that are used for imaging paragangliomas. In the second part
      we will emphasize the interest in new PET approaches (specific and non-specific),
      considering the growing knowledge about genetic background and pathophysiology,
      with the aim of understanding how tumors behave, and optimally adjusting imaging
      technique for each tumor type.

PMID- 22655254
TI  - Strategies for discovery of small molecule radiation protectors and radiation
      mitigators.
AB  - Mitochondrial targeted radiation damage protectors (delivered prior to
      irradiation) and mitigators (delivered after irradiation, but before the
      appearance of symptoms associated with radiation syndrome) have been a recent
      focus in drug discovery for (1) normal tissue radiation protection during
      fractionated radiotherapy, and (2) radiation terrorism counter measures. Several
      categories of such molecules have been discovered: nitroxide-linked hybrid
      molecules, including GS-nitroxide, GS-nitric oxide synthase inhibitors,
      p53/mdm2/mdm4 inhibitors, and pharmaceutical agents including inhibitors of the
      phosphoinositide-3-kinase pathway and the anti-seizure medicine, carbamazepine.
      Evaluation of potential new radiation dose modifying molecules to protect normal
      tissue includes: clonogenic radiation survival curves, assays for apoptosis and
      DNA repair, and irradiation-induced depletion of antioxidant stores. Studies of
      organ specific radioprotection and in total body irradiation-induced
      hematopoietic syndrome in the mouse model for protection/mitigation facilitate
      rational means by which to move candidate small molecule drugs along the drug
      discovery pipeline into clinical development.

PMID- 22655257
TI  - Stratification and Prognostic Relevance of Jass's Molecular Classification of
      Colorectal Cancer.
AB  - BACKGROUND: The current proposed model of colorectal tumorigenesis is based
      primarily on CpG island methylator phenotype (CIMP), microsatellite instability
      (MSI), KRAS, BRAF, and methylation status of 0-6-Methylguanine DNA
      Methyltransferase (MGMT) and classifies tumors into five subgroups. The aim of
      this study is to validate this molecular classification and test its prognostic
      relevance. METHODS: Three hundred two patients were included in this study.
      Molecular analysis was performed for five CIMP-related promoters (CRABP1, MLH1,
      p16INK4a, CACNA1G, NEUROG1), MGMT, MSI, KRAS, and BRAF. Methylation in at least 4
      promoters or in one to three promoters was considered CIMP-high and CIMP-low
      (CIMP-H/L), respectively. RESULTS: CIMP-H, CIMP-L, and CIMP-negative were found
      in 7.1, 43, and 49.9% cases, respectively. One hundred twenty-three tumors (41%)
      could not be classified into any one of the proposed molecular subgroups,
      including 107 CIMP-L, 14 CIMP-H, and two CIMP-negative cases. The 10 year
      survival rate for CIMP-high patients [22.6% (95%CI: 7-43)] was significantly
      lower than for CIMP-L or CIMP-negative (p = 0.0295). Only the combined analysis
      of BRAF and CIMP (negative versus L/H) led to distinct prognostic subgroups.
      CONCLUSION: Although CIMP status has an effect on outcome, our results underline
      the need for standardized definitions of low- and high-level CIMP, which clearly
      hinders an effective prognostic and molecular classification of colorectal
      cancer.

PMID- 22655258
TI  - CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical
      Patients with Stage I Non-Small Cell Lung Cancer.
AB  - Published data suggests that wedge resection for stage I non-small cell lung
      cancer (NSCLC) is associated with improved overall survival compared to
      stereotactic body radiation therapy. We report CyberKnife outcomes for high-risk
      surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed
      for staging. Three-to-five gold fiducial markers were implanted in or near tumors
      to serve as targeting references. Gross tumor volumes (GTVs) were contoured using
      lung windows; the margins were expanded by 5 mm to establish the planning
      treatment volume (PTV). Treatment plans were designed using a mean of 156 pencil
      beams. Doses delivered to the PTV ranged from 42 to 60 Gy in three fractions. The
      30 Gy isodose contour extended at least 1 cm from the GTV to eradicate
      microscopic disease. Treatments were delivered using the CyberKnife system with
      tumor tracking. Examination and PET/CT imaging occurred at 3 month follow-up
      intervals. Forty patients (median age 76) with a median maximum tumor diameter of
      2.6 cm (range, 1.4-5.0 cm) and a mean post-bronchodilator percent predicted
      forced expiratory volume in 1 s (FEV1) of 57% (range, 21-111%) were treated. A
      median dose of 48 Gy was delivered to the PTV over 3-13 days (median, 7 days).
      The 30 Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44
      months (range, 12-72 months) follow-up, the 3 year Kaplan-Meier locoregional
      control and overall survival estimates compare favorably with contemporary wedge
      resection outcomes at 91 and 75%, respectively. CyberKnife is an effective
      treatment approach for stage I NSCLC that is similar to wedge resection,
      eradicating tumors with 1-2 cm margins in order to preserve lung function.
      Prospective randomized trials comparing CyberKnife with wedge resection are
      necessary to confirm equivalence.

PMID- 22655259
TI  - Current status and future perspectives on the etiology of esophageal
      adenocarcinoma.
AB  - Esophageal adenocarcinoma is the most common type of esophageal cancer in most
      Western countries and is an important contributor to overall cancer mortality.
      Most cases of esophageal adenocarcinoma are believed to arise from Barrett's
      esophagus. Esophageal adenocarcinoma occurs more frequently in white men over 50
      years old, as well as in people with frequent symptoms of gastroesophageal
      reflux, in smokers and in people who are obese. Higher consumption of fruit and
      vegetables, use of non-steroidal anti-inflammatory drugs, and infection with
      Helicobacter pylori have all been shown to reduce the risk of esophageal
      adenocarcinoma. Here, we review the epidemiological evidence for the major risk
      factors of esophageal adenocarcinoma and also discuss perspectives for future
      research.

PMID- 22655260
TI  - Deep Sequence Analysis of Non-Small Cell Lung Cancer: Integrated Analysis of Gene
      Expression, Alternative Splicing, and Single Nucleotide Variations in Lung
      Adenocarcinomas with and without Oncogenic KRAS Mutations.
AB  - KRAS mutations are highly prevalent in non-small cell lung cancer (NSCLC), and
      tumors harboring these mutations tend to be aggressive and resistant to
      chemotherapy. We used next-generation sequencing technology to identify pathways
      that are specifically altered in lung tumors harboring a KRAS mutation. Paired
      end RNA-sequencing of 15 primary lung adenocarcinoma tumors (8 harboring mutant
      KRAS and 7 with wild-type KRAS) were performed. Sequences were mapped to the
      human genome, and genomic features, including differentially expressed genes,
      alternate splicing isoforms and single nucleotide variants, were determined for
      tumors with and without KRAS mutation using a variety of computational methods.
      Network analysis was carried out on genes showing differential expression (374
      genes), alternate splicing (259 genes), and SNV-related changes (65 genes) in
      NSCLC tumors harboring a KRAS mutation. Genes exhibiting two or more connections
      from the lung adenocarcinoma network were used to carry out integrated pathway
      analysis. The most significant signaling pathways identified through this
      analysis were the NFkappaB, ERK1/2, and AKT pathways. A 27 gene mutant KRAS
      specific sub network was extracted based on gene-gene connections from the
      integrated network, and interrogated for druggable targets. Our results confirm
      previous evidence that mutant KRAS tumors exhibit activated NFkappaB, ERK1/2, and
      AKT pathways and may be preferentially sensitive to target therapeutics toward
      these pathways. In addition, our analysis indicates novel, previously
      unappreciated links between mutant KRAS and the TNFR and PPARgamma signaling
      pathways, suggesting that targeted PPARgamma antagonists and TNFR inhibitors may
      be useful therapeutic strategies for treatment of mutant KRAS lung tumors. Our
      study is the first to integrate genomic features from RNA-Seq data from NSCLC and
      to define a first draft genomic landscape model that is unique to tumors with
      oncogenic KRAS mutations.

PMID- 22655255
TI  - The APC/C Ubiquitin Ligase: From Cell Biology to Tumorigenesis.
AB  - The ubiquitin proteasome system (UPS) is required for normal cell proliferation,
      vertebrate development, and cancer cell transformation. The UPS consists of
      multiple proteins that work in concert to target a protein for degradation via
      the 26S proteasome. Chains of an 8.5-kDa protein called ubiquitin are attached to
      substrates, thus allowing recognition by the 26S proteasome. Enzymes called
      ubiquitin ligases or E3s mediate specific attachment to substrates. Although
      there are over 600 different ubiquitin ligases, the Skp1-Cullin-F-box (SCF)
      complexes and the anaphase promoting complex/cyclosome (APC/C) are the most
      studied. SCF involvement in cancer has been known for some time while APC/C's
      cancer role has recently emerged. In this review we will discuss the importance
      of APC/C to normal cell proliferation and development, underscoring its possible
      contribution to transformation. We will also examine the hypothesis that
      modulating a specific interaction of the APC/C may be therapeutically attractive
      in specific cancer subtypes. Finally, given that the APC/C pathway is relatively
      new as a cancer target, therapeutic interventions affecting APC/C activity may be
      beneficial in cancers that are resistant to classical chemotherapy.

PMID- 22655256
TI  - Current knowledge on pancreatic cancer.
AB  - Pancreatic cancer is the fourth leading cause of cancer death with a median
      survival of 6 months and a dismal 5-year survival rate of 3-5%. The development
      and progression of pancreatic cancer are caused by the activation of oncogenes,
      the inactivation of tumor suppressor genes, and the deregulation of many
      signaling pathways. Therefore, the strategies targeting these molecules as well
      as their downstream signaling could be promising for the prevention and treatment
      of pancreatic cancer. However, although targeted therapies for pancreatic cancer
      have yielded encouraging results in vitro and in animal models, these findings
      have not been translated into improved outcomes in clinical trials. This failure
      is due to an incomplete understanding of the biology of pancreatic cancer and to
      the selection of poorly efficient or imperfectly targeted agents. In this review,
      we will critically present the current knowledge regarding the molecular,
      biochemical, clinical, and therapeutic aspects of pancreatic cancer.

PMID- 22655261
TI  - Third generation tyrosine kinase inhibitors and their development in advanced
      renal cell carcinoma.
AB  - Angiogenesis in general and the vascular endothelial growth factor (VEGF)
      signaling axis in particular is a validated target in renal cell carcinoma (RCC).
      Clear-cell carcinoma of the kidney is now recognized as a malignancy that is
      sensitive to inhibitors of the VEGF pathway. Treatment options for patients with
      metastatic renal cell carcinoma have evolved in dramatic fashion over the past 6
      years, and a new paradigm has developed. The cytokines interferon-alpha and
      interleukin-2 were previously utilized for therapy, but since December 2005, six
      new agents have been approved in the United States for the treatment of advanced
      RCC. Two are tyrosine kinase inhibitors (TKI's) including sunitinib and recently
      pazopanib, and the multikinase inhibitor sorafenib. The current review examines
      the evolving data with the next generation of TKI's, axitinib and tivozanib being
      developed for the treatment of advanced RCC. These agents were synthesized to
      provide increased target specificity and enhanced target inhibition. The
      preclinical and clinical data are examined, an overview of the development of
      these TKI's is provided, and discussion plus speculation concerning their
      potential roles as RCC therapy is provided.

PMID- 22655263
TI  - ALK Inhibitors, a Pharmaceutical Perspective.
AB  - In 2007, the ALK tyrosine kinase was described as a potential therapeutic target
      for a subset of non-small-cell lung cancer patients. Clinical proof of concept,
      culminating in the recent approval by the Food and Drug Administration of the
      Pfizer drug crizotinib followed in record time. The drug was approved together
      with a companion diagnostic for detection of patients eligible for therapy. This
      remarkable example of the coming of age of personalized medicine in cancer
      therapy is hopefully only an auspice of things to come in a rapidly developing
      field. Perhaps unsurprisingly, however, the appearance of clinical acquired
      resistance to crizotinib was observed early on in clinical testing, with the
      identification of several ALK secondary point mutations which diminish drug
      efficacy and which open the way for development of second-generation inhibitors.
      It is also emerging that acquired resistance to crizotinib may additionally occur
      through ALK-independent mechanisms, which still need to be elucidated in detail.
      Here we discuss the factors that led to such a rapid approval of a targeted
      agent, and we describe the second-generation compounds currently in development.

PMID- 22655262
TI  - Exposure to Polycyclic Aromatic Hydrocarbons Among Never Smokers in Golestan
      Province, Iran, an Area of High Incidence of Esophageal Cancer - a Cross
      Sectional Study with Repeated Measurement of Urinary 1-OHPG in Two Seasons.
AB  - Studies have suggested a possible role of polycyclic aromatic hydrocarbons (PAHs)
      in the etiology of esophageal cancer in Golestan Province, Iran, where incidence
      of this cancer is very high. In order to investigate the patterns of non-smoking
      related exposure to PAHs in Golestan, we conducted a cross-sectional study
      collecting questionnaire data, genotyping polymorphisms related to PAH
      metabolism, and measuring levels of 1-hydroxypyrene glucuronide (1-OHPG), a PAH
      metabolite, in urine samples collected in two seasons from the same group of 111
      randomly selected never-smoking women. Beta-coefficients for correlations between
      1-OHPG as dependent variable and other variables were calculated using linear
      regression models. The creatinine-adjusted 1-OHPG levels in both winter and
      summer samples were approximately 110 MUmol/molCr (P for seasonal difference =
      0.40). In winter, red meat intake (beta = 0.208; P = 0.03), processed meat intake
      (beta = 0.218; P = 0.02), and GSTT1-02 polymorphism ("null" genotype: beta =
      0.228; P = 0.02) showed associations with 1-OHPG levels, while CYP1B1-07
      polymorphism (GG versus AA + GA genotypes: beta = -0.256; P = 0.008) showed an
      inverse association. In summer, making bread at home (> weekly versus never: beta
      = 0.203; P = 0.04), second-hand smoke (exposure to >=3 cigarettes versus no
      exposure: beta = 0.254; P = 0.01), and GSTM1-02 "null" genotype (beta = 0.198; P
      = 0.04) showed associations with 1-OHPG levels, but GSTP1-02 polymorphism (CT +
      TT versus CC: beta = -0.218; P = 0.03) showed an inverse association. This study
      confirms high exposure of the general population in Golestan to PAHs and suggests
      that certain foods, cooking methods, and genetic polymorphisms increase exposure
      to PAHs.

PMID- 22655264
TI  - Neuroendocrine tumors: a focus on liver metastatic lesions.
AB  - Transhepatic radionuclide infusion has been introduced as a new treatment
      approach for unresectable liver neuroendocrine metastatic lesions with the
      prerequisite of a positive In-111 Pentetreotide (Octreoscan). Patients with
      multiple liver neuroendocrine metastases can be locally treated after selective
      hepatic artery catheterization and infusion of radiolabeled somatostatin analogs,
      and in case of extra-hepatic secondary spread, after simple i.v. application.
      According to the world wide references, the average dose per session to each
      patient is 6.3 +/- 0.3 GBq (~160-180 mCi) of In-111-DTPA-Phe1-Pentetreotide, 10-
      to 12-fold in total, administered monthly or of 4.1 +/- 0.2 GBq (~105-116 mCi) of
      Y-90 DOTA TOC, threefold in total, or of 7.0 +/- 0.4 GBq (~178-200 mCi) of Lu-177
      DOTA TATE, fourfold to sixfold in total (the choice of which being based on the
      tumor size, assessed by CT or MRI). Follow-up at monthly intervals has to be
      performed by means of ultrasonography (US). Treatment response has to be assessed
      according to the WHO criteria (RECIST or SWOG).

PMID- 22655265
TI  - A Screening Method for the ALK Fusion Gene in NSCLC.
AB  - Lung cancer research has recently made significant progress in understanding the
      molecular pathogenesis of lung cancer and in developing treatments for it. Such
      achievements are directly utilized in clinical practice. Indeed, the echinoderm
      microtubule-associated protein-like 4-anaplastic lymphoma kinase (ALK) fusion
      gene was first described in non-small cell lung cancer in 2007, and a molecularly
      targeted drug against the fusion was approved in 2011. However, lung cancer with
      the ALK fusion constitutes only a small fraction of lung cancers; therefore,
      efficient patient selection is crucial for successful treatment using the ALK
      inhibitor. Currently, RT-PCR, fluorescent in situ hybridization (FISH), and
      immunohistochemistry are commonly used to detect the ALK fusion. Although FISH is
      currently the gold standard technique, there are no perfect methods for detecting
      these genetic alterations. In this article, we discuss the advantages and
      disadvantages of each method and the possible criteria for selecting patients who
      are more likely to have the ALK fusion. If we can successfully screen patients,
      then ALK inhibitor treatment will be the best example of personalized therapy in
      terms of selecting patients with an uncommon genotype from a larger group with
      the same tumor phenotype. In other words, the personalized therapy may offer a
      new challenge for current clinical oncology.

PMID- 22655266
TI  - CyberKnife Boost for Patients with Cervical Cancer Unable to Undergo
      Brachytherapy.
AB  - Standard radiation therapy for patients undergoing primary chemosensitized
      radiation for carcinomas of the cervix usually consists of external beam
      radiation followed by an intracavitary brachytherapy boost. On occasion, the
      brachytherapy boost cannot be performed due to unfavorable anatomy or because of
      coexisting medical conditions. We examined the safety and efficacy of using
      CyberKnife stereotactic body radiotherapy (SBRT) as a boost to the cervix after
      external beam radiation in those patients unable to have brachytherapy to give a
      more effective dose to the cervix than with conventional external beam radiation
      alone. Six consecutive patients with anatomic or medical conditions precluding a
      tandem and ovoid boost were treated with combined external beam radiation and
      CyberKnife boost to the cervix. Five patients received 45 Gy to the pelvis with
      serial intensity-modulated radiation therapy boost to the uterus and cervix to a
      dose of 61.2 Gy. These five patients received an SBRT boost to the cervix to a
      dose of 20 Gy in five fractions of 4 Gy each. One patient was treated to the
      pelvis to a dose of 45 Gy with an external beam boost to the uterus and cervix to
      a dose of 50.4 Gy. This patient received an SBRT boost to the cervix to a dose of
      19.5 Gy in three fractions of 6.5 Gy. Five percent volumes of the bladder and
      rectum were kept to <=75 Gy in all patients (i.e., V75 Gy <= 5%). All of the
      patients remain locally controlled with no evidence of disease following
      treatment. Grade 1 diarrhea occurred in 4/6 patients during the conventional
      external beam radiation. There has been no grade 3 or 4 rectal or bladder
      toxicity. There were no toxicities observed following SBRT boost. At a median
      follow-up of 14 months, CyberKnife radiosurgical boost is well tolerated and
      efficacious in providing a boost to patients with cervix cancer who are unable to
      undergo brachytherapy boost. Further follow-up is required to see if these
      results remain durable.

PMID- 22655267
TI  - CRL Ubiquitin Ligases and DNA Damage Response.
AB  - Cullin/RING ubiquitin ligases (CRL) comprise the largest subfamily of ubiquitin
      ligases. CRLs are involved in cell cycle regulation, DNA replication, DNA damage
      response (DDR), development, immune response, transcriptional regulation,
      circadian rhythm, viral infection, and protein quality control. One of the main
      functions of CRLs is to regulate the DDR, a fundamental signaling cascade that
      maintains genome integrity. In this review, we will discuss the regulation of CRL
      ubiquitin ligases and their roles in control of the DDR.

PMID- 22655268
TI  - Cytotoxic Capacity of IL-15-Stimulated Cytokine-Induced Killer Cells Against
      Human Acute Myeloid Leukemia and Rhabdomyosarcoma in Humanized Preclinical Mouse
      Models.
AB  - Allogeneic stem cell transplantation (allo-SCT) has become an important treatment
      modality for patients with high-risk acute myeloid leukemia (AML) and is also
      under investigation for soft tissue sarcomas. The therapeutic success is still
      limited by minimal residual disease (MRD) status ultimately leading to patients'
      relapse. Adoptive donor lymphocyte infusions based on MRD status using IL-15
      expanded cytokine-induced killer (CIK) cells may prevent relapse without causing
      graft-versus-host-disease (GvHD). To generate preclinical data we developed mouse
      models to study anti-leukemic- and anti-tumor-potential of CIK cells in vivo.
      Immunodeficient mice (NOD/SCID/IL-2Rgammac(-), NSG) were injected intravenously
      with human leukemic cell lines THP-1, SH-2 and with human rhabdomyosarcoma (RMS)
      cell lines RH41 and RH30 at minimal doses required for leukemia or tumor
      engraftment. Mice transplanted with THP-1 or RH41 cells were randomly assigned
      for analysis of CIK cell treatment. Organs of mice were analyzed by flow
      cytometry as well as quantitative polymerase chain reaction for engraftment of
      malignant cells and CIK cells. Potential of CIK cells to induce GvHD was
      determined by histological analysis. Tissues of the highest degree of THP-1 cell
      expansion included bone marrow followed by liver, lung, spleen, peripheral blood
      (PB), and brain. RH30 and RH41 engraftment mainly took place in liver and lung,
      but was also detectable in spleen and PB. In spite of delayed CIK cell expansion
      compared with malignant cells, CIK cells injected at equal amounts were
      sufficient for significant reduction of RH41 cells, whereas against fast
      expanding THP-1 cells 250 times more CIK than THP-1 cells were needed to achieve
      comparable results. Our preclinical in vivo mouse models showed a reliable 100%
      engraftment of malignant cells which is essential for analysis of anti-cancer
      therapy. Furthermore our data demonstrated that IL-15-activated CIK cells have
      potent cytotoxic capacity against AML and RMS cells without causing GvHD.

PMID- 22655269
TI  - Epithelial-mesenchymal transition in ovarian carcinoma.
AB  - Ovarian cancer is the most lethal gynecologic malignancy, with the majority of
      patients dying within 5 years of diagnosis. This poor survival of patients
      diagnosed with this malignancy is attributed to diagnosis at advanced stage, when
      the tumor has metastasized, and to chemotherapy resistance, either primary or
      developing along tumor progression. However, ovarian carcinomas, constituting the
      vast majority of ovarian cancers, additionally have unique biology, one aspect of
      which is the ability to co-express epithelial and mesenchymal determinants.
      epithelial-mesenchymal transition (EMT), a physiological process by which
      mesenchymal cells are formed and migrate to target organs during embryogenesis,
      is involved in cancer cell invasion and metastasis. However, these changes do not
      fully occur in ovarian carcinoma, and are even reversed in tumor cells present in
      malignant peritoneal and pleural effusions. This review summarizes current
      knowledge in this area, including the characteristics of EMT related to adhesion,
      transcriptional regulation and chemoresistance, and their clinical relevance, as
      well as the recently observed regulation of EMT by microRNA.

PMID- 22655270
TI  - ROR1 and ROR2 in Human Malignancies: Potentials for Targeted Therapy.
AB  - Targeted therapies require cellular protein expression that meets specific
      requirements that will maximize effectiveness, minimize off-target toxicities,
      and provide an opportunity for a therapeutic effect. The receptor tyrosine kinase
      like orphan receptors (ROR) are possible targets for therapy that may meet such
      requirements. RORs are transmembrane proteins that are part of the receptor
      tyrosine kinase (RTK) family. The RORs have been shown to play a role in tumor
      like behavior, such as cell migration and cell invasiveness and are normally not
      expressed in normal adult tissue. As part of the large effort in target
      discovery, ROR proteins have recently been found to be expressed in human
      cancers. Their unique expression profiles may provide a novel class of
      therapeutic targets for small molecules against the kinase or for antibody-based
      therapies against these receptors. Being restricted on tumor cells and not on
      most normal tissues, RORs are excellent targets for the treatment of minimal
      residual disease, the final hurdle in the curative approach to many cancers,
      including solid tumors such as neuroblastoma. In this review, we summarize the
      biology of RORs as they relate to human cancer, and highlight the therapeutic
      approaches directed toward them.

PMID- 22655272
TI  - Plasma Cytokine Concentrations in Workers Exposed to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD).
AB  - OBJECTIVES: Few epidemiological studies have studied the effect of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) on blood cytokine levels. In this study we
      investigated changes in plasma levels of a large panel of cytokines, chemokines,
      and growth factors among workers from a Dutch historical cohort occupationally
      exposed to chlorophenoxy herbicides and contaminants including TCDD. METHODS:
      Eighty-five workers who had been exposed to either high (n = 47) or low (n = 38)
      TCDD levels more than 30 years before serum collection were included in the
      current investigation. Plasma level of 16 cytokines, 10 chemokines, and 6 growth
      factors were measured. Current plasma levels of TCDD (TCDD(current)) were
      determined by high-resolution gas chromatography/isotope-dilution high-resolution
      mass spectrometry. TCDD blood levels at the time of last exposure (TCDD(max))
      were estimated using a one-compartment first order kinetic model. RESULTS: Blood
      levels of most analytes had a negative association with current and estimated
      past maximum TCDD levels. These decreases reached formal statistical significance
      for fractalkine, transforming growth factor alpha (TGF-alpha), and fibroblast
      growth factor 2 (FGF2) with increasing TCDD levels. CONCLUSION: Our study showed
      a general reduction in most analyte levels with the strongest effects for
      fractalkine, FGF2, and TGF-alpha. These findings suggest that TCDD exposure could
      suppress the immune system and that chemokine and growth factor-dependent
      cellular pathway changes by TCDD may play role in TCDD toxicity and associated
      health effects.

PMID- 22655271
TI  - New Concepts for Translational Head and Neck Oncology: Lessons from HPV-Related
      Oropharyngeal Squamous Cell Carcinomas.
AB  - Human papillomavirus (HPV) infection is well established as an etiological agent
      responsible for a number of pathologies affecting the stratified epithelia of
      skin and anogenital sites. More recently, the infection by (mucosal) high-risk
      HPV types has also been found to be causally associated with squamous cell
      carcinoma in the head and neck region (HNSCC), especially in the oropharynx.
      Intriguingly, HPV-related oropharyngeal squamous cell carcinomas (OPSCC)
      represent a distinct clinical entity compared to HPV-negative tumors with
      particular regard to treatment-response and survival outcome. The association
      between HPV infection and OPSCC may therefore have important implications for the
      prevention and/or treatment of OPSCC. The improved survival of patients with HPV
      related tumors also raises the question, as to whether a better understanding of
      the underlying differences may help to identify new therapeutic concepts that
      could be used in targeted therapy for HPV-negative and improved therapy for HPV
      positive cancers. This review summarizes the most recent advances in our
      understanding of the molecular principles of HPV-related OPSCC, mainly based on
      functional genomic approaches, but also emphasizes the significant role played by
      the tumor microenvironment, especially the immune system, for improved clinical
      outcome and differential sensitivity of HPV-related tumors to current treatment
      options.

PMID- 22655273
TI  - Current status of intensified neo-adjuvant systemic therapy in locally advanced
      rectal cancer.
AB  - The addition of 5-fluorouracil (5-FU) or its prodrug capecitabine to radiotherapy
      (RT) is a standard approach in the neo-adjuvant treatment of patients with rectal
      tumors extending beyond the muscularis propria (stage II) and/or with clinical
      evidence of regional lymph node metastases (stage III). According to European
      randomized trials, the combined treatment modality resulted in favorable local
      control rates as compared with radiotherapy (RT) alone, but no improvement was
      found regarding the occurrence of distant metastases or overall survival. In an
      effort to further enhance the response rates and to decrease the high incidence
      of distant metastases in locally advanced rectal cancer patients, the addition of
      other chemotherapeutical drugs and biologic agents as radiation sensitizers to
      neo-adjuvant 5-FU based chemoradiotherapy (CRT) has been recently investigated.
      The role of those agents is however questionable as first results from phase III
      data do not show improvement on pathologic complete remission and circumferential
      resection margin negative resection rates as compared to 5-FU based CRT,
      nevertheless an increased toxicity.

PMID- 22655274
TI  - Management of biochemical recurrence after primary localized therapy for prostate
      cancer.
AB  - Clinically localized prostate cancer is typically managed by well established
      therapies like radical prostatectomy, brachytherapy, and external beam radiation
      therapy. While many patients can be cured with definitive local therapy, some
      will have biochemical recurrence (BCR) of disease detected by a rising serum
      prostate-specific antigen (PSA). Management of these patients is nuanced and
      controversial. The natural history indicates that a majority of patients with BCR
      will not die from prostate cancer but from other causes. Despite this, a vast
      majority of patients with BCR are empirically treated with non-curable systemic
      androgen deprivation therapy (ADT), with its myriad of real and potential side
      effects. In this review article, we examined the very definition of BCR after
      definitive local therapy, the current status of imaging studies in its
      evaluation, the need for additional therapies, and the factors involved in the
      decision making in the choice of additional therapies. This review aims to help
      clinicians with the management of patients with BCR. The assessment of prognostic
      factors including absolute PSA level, time to recurrence, PSA kinetics,
      multivariable nomograms, imaging, and biopsy of the prostatic bed may help
      stratify the patients into localized or systemic recurrence. Patients with low
      risk of systemic disease may be cured by a salvage local therapy, while those
      with higher risk of systemic disease may be offered the option of ADT or a
      clinical trial. An algorithm incorporating these factors is presented.

PMID- 22655275
TI  - Inter and intratumour heterogeneity: a barrier to individualized medical therapy
      in renal cell carcinoma?

PMID- 22655276
TI  - Differing von hippel lindau genotype in paired primary and metastatic tumors in
      patients with clear cell renal cell carcinoma.
AB  - In sporadic clear cell renal cell carcinoma (CCRCC), the von Hippel Lindau (VHL)
      gene is inactivated by mutation or methylation in the majority of primary (P)
      tumors. Due to differing effects of wild-type (WT) and mutant (MT) VHL gene on
      downstream signaling pathways regulating angiogenesis, VHL gene status could
      impact clinical outcome. In CCRCC, comparative genomic hybridization analysis
      studies have reported genetic differences between paired P and metastatic (M)
      tumors. We thus sequenced the VHL gene in paired tumor specimens from 10 patients
      to determine a possible clonal relationship between the P tumor and M lesion(s)
      in patients with CCRCC. Using paraffin-embedded specimens, genomic DNA from
      microdissected samples (>80% tumor) of paired P tumor and M lesions from all 10
      patients, as well as in normal tissue from 6 of these cases, was analyzed. The
      DNA was used for PCR-based amplification of each of the 3 exons of the VHL gene.
      Sequences derived from amplified samples were compared to the wild-type VHL gene
      sequence (GenBank Accession No. AF010238). Methylation status of the VHL gene was
      determined using VHL methylation-specific PCR primers after DNA bisulfite
      modification. In 4/10 (40%) patients the VHL gene status differed between the P
      tumor and the M lesion. As expected, when the VHL gene was mutated in both the P
      tumor and M lesion, the mutation was identical. Further, while the VHL genotype
      differed between the primary tumor in different kidneys or multiple metastatic
      lesions in the same patient, the VHL germline genotype in the normal adjacent
      tissue was always wild-type irrespective of the VHL gene status in the P tumor.
      These results demonstrate for the first time that the VHL gene status can be
      different between paired primary and metastatic tissue in patients with CCRCC.

PMID- 22655277
TI  - Locally advanced cancer of the esophagus, current treatment strategies, and
      future directions.
AB  - For patients with locally advanced esophageal cancer no clear standard of care
      exists. Notwithstanding several negative phase III studies the data provide
      support for so-called trimodality treatment and this is probably the most common
      approach. Even the role of surgery has been questioned. These alternative
      approaches are set against a changing epidemiological background whereby
      adenocarcinoma has become the predominant tumor type, at least in the western
      world. In recent times an emphasis has been placed on the better selection of
      patients, predominantly based on data that shows a markedly improved survival in
      those who exhibit a response to neo-adjuvant therapy. In this article we review
      the major studies and discuss new approaches to the management of patients with
      locally advanced cancer of the esophagus.

PMID- 22655278
TI  - Diagnosis and management of gallbladder polyps.
AB  - Gallbladder cancer is a rather uncommon disease, when it gives symptoms it has
      usually reached an incurable stage. Therefore, every attempt must be made to find
      the asymptomatic stages and look for premalignant gallbladder polyps. Even if
      gallbladder cancer is a rare disease, gallbladder polyps are common, only a few
      polyps develop to cancer. This makes gallbladder polyps another problem: which
      are the polyps that must be surgically removed, which shall be followed-up, or
      for how long? The author used the keyword "gallbladder polypsn" in PubMed and
      reviewed the scientific literatures published from January 2000 to December 2011.
      The present review article has summarized almost all respects of gallbladder
      polyp, including the risk factors, clinical diagnosis and management, and
      comments made from the author, in which clinical treatments are recommended. It
      is author's purpose that the 11-year-knowledge about gallbladder polyps
      summarized from all worlds' literatures is enough to know how clinicians will
      handle the next patient with gallbladder polyp.

PMID- 22655279
TI  - Duplex Detection of TP53 Arg72Pro and 16 bp Del/Ins Polymorphisms by a Simple
      Optimized PCR-RFLP Method.
AB  - BACKGROUND: The tumor suppressor gene (TP53) encodes p53, the central protein in
      the apoptotic pathway which has been shown to be of crucial importance in the
      development of cancers in addition to a variety of neurodegenerative disorders.
      Two most commonly studied polymorphisms that were shown to affect the biochemical
      functions of p53 protein are the exon 4 Arg72pro and Intron 3 16 bp Del/Ins
      polymorphisms. AIMS: The aim of the present work is to develop a new optimized
      method for the simultaneous detection of the two important polymorphisms in the
      TP53 gene in a single reaction. MATERIALS AND METHODS: The proposed method is
      based on amplification of a single PCR amplicon and the use of a unique
      restriction enzyme with restriction sites that facilitate simultaneous detection.
      RESULTS: The proposed method offers fast, economical, and simple simultaneous
      detection. Validation by methods commonly used in the literature showed perferct
      concordance in genotyping results. CONCLUSION: The proposed method can serve as
      an invaluable tool for the investigation of TP53 Arg72Pro-16 bp Del/Ins
      haplotype, and the combined effects of the two polymorphisms offering extreme
      ease and simplicity over the currently used methods which are based on two
      separate detections.

PMID- 22655280
TI  - Early prediction of acute kidney injury by clinical features of snakebite
      patients at the time of hospital admission.
AB  - BACKGROUND: Snakebite is a major health problem in India. Venomous snakebite,
      which is an important medical hazard in several tropical countries including
      India, affects thousands of people per year and some of them develop acute kidney
      injury (AKI). AIMS: This study was performed to find out 1) early clinical
      predictors for acute kidney injury in snakebite patients at the time of hospital
      admission and 2) incidence of acute kidney injury in snakebite patients.
      MATERIALS AND METHODS: 171 consecutively admitted non-diabetic, non-hypertensive
      snakebite patients were examined. Multivariate linear regression analysis with 95
      percent confidence interval (CI) was done for statistical analysis. Analyses were
      performed by software Statistical Package for the Social Sciences (SPSS) (17(th)
      version for Windows). RESULTS: Incidence of acute kidney injury was 43.27%.
      Development of acute kidney injury was independently associated with 20 min whole
      blood clotting test (20 min WBCT) (P value = 0.029; CI 95%), dark or brown color
      urine (P value = 0.000; CI 95%), and time interval between snakebite and anti
      snake venom administration (P value = 0.000; CI 95%). Age (P value = 0.011; CI
      95%) and presence of neurological signs (P value = 0.000; CI 95%) were negatively
      correlated with development of acute kidney injury. CONCLUSION: Incidence of
      acute kidney injury is slightly higher in our study than previous studies. Early
      prediction of acute kidney injury development in snakebite patients can be done
      by presence of black or brown urine, 20 min WBCT > 20 min, and increased time
      interval between snakebite and administration of anti-snake venom at the time of
      hospital admission. Young age group of snakebite patients develops acute kidney
      injury more commonly.

PMID- 22655281
TI  - HIV-Tuberculosis: A Study of Chest X-Ray Patterns in Relation to CD4 Count.
AB  - BACKGROUND: Fight against human immunodeficiency virus (HIV) is incomplete
      without addressing problems associated with difficult diagnosis of tuberculosis
      in HIV-Tuberculosis coinfected patients. Chest X-ray is a primary tool to
      evaluate tuberculosis in HIV. AIM: To assess and compare various radiological
      patterns of pulmonary tuberculosis in HIV patients and compare these patterns in
      relation to CD4 counts. MATERIALS AND METHODS: Prospective cohort study was
      conducted in a tertiary hospital in South India from September 2009 to July 2011
      with 200 HIV positive patients. WHO guidelines were used for diagnosis of HIV and
      tuberculosis. RESULTS: 27% of the patients had sputum positive pulmonary
      tuberculosis, with higher incidence (33%) among CD4 less than 200 as compared to
      CD4 more than 200 (14%). Infiltration (39%) followed by consolidation (30%),
      cavity (11%), and lymphadenopathy (9%) seen with CD4 less than 200. Infiltration
      (37.5%) followed by cavity (25%) and miliary (25%) with CD4 above 200. Bilateral
      (68.5%) and mid and lower zones or all zone involvement more commonly seen.
      CONCLUSION: In patients with CD4 lower than 200 noncavitory infiltration and
      consolidation predominated. Involvement of lungs was atypical; diffuse or mid and
      lower zone involvement than classical upper lobe involvement. A high index of
      suspicion is necessary for the accurate and timely diagnosis of tuberculosis in
      HIV positive patients.

PMID- 22655282
TI  - Transobturator Tape in Treatment of Stress Urinary Incontinence: It is Time for a
      New Gold Standard.
AB  - BACKGROUND: Stress urinary incontinence (SUI) can significantly impair the
      quality of life. A variety of treatments, both medical and surgical, have been
      used to manage it. The transobturator sling, which is a subfascial sling, is
      relatively a new surgical technique with minimal access. AIM: The objective of
      this study was to evaluate the effectiveness of transobturator tape (TOT) in the
      treatment of female SUI and to analyze functional results. MATERIALS AND METHODS:
      A total of 59 patients were applied TOT by outside-in technique and various
      outcome parameters recorded. These patients were followed up 6 months after
      surgery. RESULTS: Success rate of TOT was 93.2% (95% CI: 86.4-99.5). A total of
      51 patients (86.4%) were completely satisfied, whereas 4 (6.8%) were partially
      satisfied and 4 were unsatisfied with surgical outcome. The procedure-related
      complications were few and could be managed in the same sitting. CONCLUSION: The
      transobturator approach is an effective treatment of SUI with low morbidity, and
      it has all the potential to be the new Gold Standard in the treatment of female
      SUI.

PMID- 22655283
TI  - Assessment of Prevalence of Non-tuberculous Mycobacteria in Archival Acid-fast
      Bacilli Positive Smear Slides by TaqMan Real-time PCR Assay.
AB  - BACKGROUND: The emergence of non-tuberculous mycobacteria as clinically relevant
      pathogens has necessitated us for the study of these organisms in the context of
      their environment. Differentiation of Mycobacterium tuberculosis complex and non
      tuberculous mycobacteria is important especially when we have a positive smear
      slide test result. AIM: In this study, we planned to survey the prevalence of
      tuberculosis and non-tuberculous mycobacteria among archival acid-fast bacilli
      positive smear slides. MATERIALS AND METHODS: A number of 200 acid-fast bacilli
      positive smear slides were collected from different parts of Sistan and
      Baluchestan Province, the biggest province of Iran with the highest incidence of
      tuberculosis. The presence of mycobacterial IS6110 was evaluated in slides'
      scraped material by TaqMan real-time polymerase chain reaction assay. RESULTS:
      The real-time polymerase chain reaction tests of archival acid-fast bacilli
      positive smear slides showed that 171 slides from 200 examined slides had M.
      tuberculosis DNA and in the remaining 29 examined slides, M. tuberculosis DNA was
      not found. CONCLUSION: Our findings showed that there was no M. tuberculosis DNA
      in 14.5% of archival AFB positive smear slides, and this finding necessitates us
      to reviewing our diagnostic and anti- tuberculous protocols.

PMID- 22655284
TI  - Multiple unerupted teeth with amelogenesis imperfecta in siblings.
AB  - Amelogenesis imperfecta encompasses a group of inherited abnormalities that are
      generally considered to primarily affect the formation and/or calcification of
      enamel. This case report describes the unusual presentation of amelogenesis
      imperfecta in siblings as multiple unerupted teeth, multiple pulpal
      calcifications, and multiple dilacerations of roots along with the defect in the
      enamel. The intent of our report is to highlight a rare co-occurrence of
      amelogenesis imperfecta with multiple morphologic alterations in siblings.

PMID- 22655285
TI  - Familial xanthelasma with dyslipidemia: just another family trait?
AB  - Some external features serve as a warning sign for accelerated atherosclerosis.
      Their early recognition may help in early detection and primary
      prevention/preemptive treatment of coronary artery disease (CAD). A 35-year-old
      nonsmoker, nonalcoholic, nonhypertensive, nondiabetic male presented with chest
      pain and was diagnosed to have acute ST elevation inferior wall myocardial
      infarction. His father had died of CAD at 40 years of age. The patient had
      bilateral extensive xanthelasma and gynoid obesity. His mother and younger
      brother also had evidence of bilateral xanthelasma; both turned out to be
      dyslipidemic - the younger brother qualifying for therapeutic intervention for
      dyslipidemia at 26 years of age. This case highlights the importance of familial
      xanthelasma as a cutaneous marker for underlying dyslipidemia and accelerated
      atherosclerosis in the young.

PMID- 22655286
TI  - A primary synovial sarcoma of lung.
AB  - Primary pulmonary synovial sarcoma is an extremely rare tumor. The diagnosis is
      established only after sarcoma like primary lung malignancies and metastatic
      sarcoma have been excluded. It has four subtypes: monophasic fibrous, monophasic
      epithelial, biphasic, and poorly differentiated subtypes, We report a case of a
      55-year-old man, who complained of left-sided chest pain and shortness of breath,
      had a large heterogeneous mass, occupying most of left hemithorax, associated
      with ipsilateral pleural effusion, seen on contrast enhanced computed tomogram of
      thorax. Computed tomography guided tru-cut biopsy revealed spindle cell sarcoma.
      On immunohistochemistry, tumor cells expressed epithelial membrane antigen, CD99,
      bcl-2 and Calponin and were immunonegative for cytokeratin. So, final diagnosis
      was primary pulmonary synovial sarcoma, Primary pulmonary synovial sarcoma is a
      rarely reported case of malignant neoplasm of lung. Histopathology,
      immunohistochemistry, and cytogenetics, if possible, are essential for
      confirmation of its diagnosis.

PMID- 22655287
TI  - Methodological issues in treatment adherence studies.

PMID- 22655288
TI  - Homogeneous fluorescence-based immunoassay via inner filter effect of gold
      nanoparticles on fluorescence of CdTe quantum dots.
AB  - Homogeneous immunoassays are becoming more and more attractive for modern medical
      diagnosis because they are superior to heterogeneous immunoassays in sample and
      reagent consumption, analysis time, portability and disposability. Herein, a
      universal platform for homogeneous immunoassay, using human immunoglobulin (IgG)
      as a model analyte, has been developed. This assay relies upon the inner filter
      effect (IFE) of gold nanoparticles (AuNPs) on CdTe QDs fluorescence. The
      immunoreaction of antigen and antibody can induce the aggregation of antibody
      functionalized AuNPs, and after aggregation the IFE of AuNPs on CdTe QDs
      fluorescence is greatly enhanced, resulting in a decrease of fluorescence
      intensity in the system. Based on this phenomenon, a wide dynamic range of 1-100
      pg mL(-1) for determination of IgG can be obtained. The proposed method shows a
      detection limit of 0.3 pg mL(-1) for human IgG, which is much lower than the
      corresponding absorbance-based approach and compares favorably with other
      reported fluorescent methods. This immunoassay method is simple, rapid, cheap,
      and sensitive. The proposed method has been successfully applied to measuring IgG
      in serum samples, and the obtained results agreed well with those of the enzyme
      linked immunosorbent assay (ELISA).

PMID- 22655289
TI  - Generating contrast in hyperpolarized 13C MRI using ligand-receptor interactions.
AB  - We report the imaging of beta-cyclodextrin-benzoic acid binding at 14T using
      hyperpolarized (13)C magnetic resonance (MR). Benzoic acid was polarized using a
      dynamic nuclear polarization (DNP) approach and combined with beta-cyclodextrin
      in aqueous solution. As anticipated, decreases in the spin-lattice relaxation
      constant (T(1)) were observed with decreases in the ligand-receptor ratio. The
      calculated log K was approximately 1.7, similar to previously reported binding
      constants. Hyperpolarized [1-(13)C] benzoic acid was used to interrogate
      solutions of variable beta-cyclodextrin concentrations, with the mixtures imaged
      at 14T using a 3D frequency-selective MR sequence. Differences in beta
      cyclodextrin concentration were easily visualized. These results suggest that
      hyperpolarized (13)C MR could be used in vivo to determine the presence and
      density of receptors for a given ligand-receptor pair.

PMID- 22655290
TI  - Highly sensitive, selective, and rapid fluorescence Hg2+ sensor based on DNA
      duplexes of poly(dT) and graphene oxide.
AB  - Coupling T base with Hg(2+) to form stable T-Hg(2+)-T complexes represents a new
      direction in detection of Hg(2+). Here a graphene oxide (GO)-based fluorescence
      Hg(2+) analysis using DNA duplexes of poly(dT) that allows rapid, sensitive, and
      selective detection is first reported. The Hg(2+)-induced T(15)-(Hg(2+))(n)-T(15)
      duplexes make T(15) unable to hybridize with its complementary A(15) labelled
      with 6'-carboxyfluorescein (FAM-A(15)), which has low fluorescence in the
      presence of GO. On the contrary, when T(15) hybridizes with FAM-A(15) to form
      double-stranded DNA because of the absence of Hg(2+), the fluorescence largely
      remains in the presence of GO. A linear range from 10 nM to 2.0 MUM (R(2) =
      0.9963) and a detection limit of 0.5 nM for Hg(2+) were obtained under optimal
      experimental conditions. Other metal ions, such as Al(3+), Ag(+), Ca(2+), Ba(2+),
      Mg(2+), Zn(2+), Mn(2+), Co(2+), Pb(2+), Ni(2+), Cu(2+), Cd(2+), Cr(3+), Fe(2+),
      and Fe(3+), had no significant effect on Hg(2+) detection. Moreover, the sensing
      system was used for the determination of Hg(2+) in river water samples with
      satisfactory results.

PMID- 22655291
TI  - Asymmetric transformations involving 1,2-dicarbonyl compounds as pronucleophiles.
AB  - This article concentrates on the versatile nucleophilic reactivity of 1,2
      dicarbonyl compounds in various asymmetric transformations. Although
      underexploited in comparison to their 1,3-dicarbonyl homologues, the presence of
      adjacent multiple reactive centres allows the selection of specific activation
      modes for enhancing the reactivity of these important ambident pronucleophiles.
      They can be involved in selective formation of C-C, C-O or C-N bonds leading to
      various optically active targets in the acyclic and cyclic series including three
      to seven-membered ring systems. Recent contributions in the field of
      biochemical, organometallic and organic catalytic transformations as well as some
      relevant stoichiometric approaches are discussed from synthetic and mechanistic
      point of views highlighting some important stereochemical issues.

PMID- 22655292
TI  - High capacity gas storage in corrugated porous graphene with a specific surface
      area-lossless tightly stacking manner.
AB  - We report for the first time an experimental investigation of gas storage in
      porous graphene with nanomeshes. High capacity methane storage (236 v(STP)/v) and
      a high selectivity to carbon dioxide adsorption were obtained in the nanomesh
      graphene with a high specific surface area (SSA) and a SSA-lossless tightly
      stacking manner.

PMID- 22655293
TI  - A facile and ecofriendly functionalization of multiwalled carbon nanotubes by an
      old mesoionic compound.
AB  - This work reports for the first time a straightforward solvent-free chemical
      procedure to gain access to Delta-1-pyrroline grafted onto multiwalled carbon
      nanotubes by the 1,3-dipolar cycloaddition of the mesoionic 4-methyl-2
      phenyloxazol-5(4H)-one.

PMID- 22655294
TI  - Reaction-based two-photon probes for in vitro analysis and cellular imaging of
      monoamine oxidase activity.
AB  - Reaction-based fluorescent probes for monoamine oxidases A and B are developed
      based on a new two-photon absorbing compound and its precursor. The probes show
      turn-on fluorescence response to the enzymes owing to the two-photon absorbing
      compound produced by the enzymatic activity, as monitored by one- as well as two
      photon microscopy for the first time.

PMID- 22655295
TI  - A rigid donor-acceptor daisy chain dimer.
AB  - A functionalised cyclobis(paraquat-p-phenylene) attached by a rigid linker to a
      tetrathiafulvalene unit, which is incapable of self-complexation, forms
      preferentially a [c2]daisy chain which undergoes rapid disassociation and
      reassociation on the (1)H NMR time-scale above room temperature.

PMID- 22655296
TI  - Controlling growth of molecular crystal aggregates for efficient optical
      waveguides.
AB  - Controllable crystal aggregate structures which show highly uniform crystal
      tubule, rod and cubic like architectures were achieved and the well-defined
      microrods exhibit outstanding optical waveguide properties.

PMID- 22655297
TI  - A "non-sticky" superhydrophobic surface prepared by self-assembly of fluoroalkyl
      phosphonic acid on a hierarchically micro/nanostructured alumina gel film.
AB  - A hierarchically micro/nanostructured alumina gel film was prepared by using a
      simple sol-gel process; upon self-assembly of fluoroalkyl phosphonic acid, a "non
      sticky" superhydrophobic surface was obtained.

PMID- 22655298
TI  - Multielectron reduction of diazoalkane and azides via reversible cyclometalation
      in ditantalum complexes.
AB  - Reactions of the cyclometalated hydride complexes with diazo and azide substrates
      are reported. While diazoalkane undergoes four-electron N-N bond cleavage, azides
      undergo two-electron N(2) extrusion.

PMID- 22655299
TI  - The halogen bond made visible: experimental charge density of a very short
      intermolecular Cl...Cl donor-acceptor contact.
AB  - [ZnCl(2)(3,4,5-trichloropyridine)(2)] features short intermolecular Cl...Cl
      contacts between halogen atoms of different nature, and a charge density study
      provides experimental evidence for the accepted model of the halogen bonds: an
      arene-bonded Cl atom acts as a donor of electron density towards the "sigma hole"
      of a chlorido ligand attached to a neighbouring Zn(II) cation.

PMID- 22655300
TI  - [Not Available].

PMID- 22655301
TI  - [Not Available].

PMID- 22655302
TI  - [Not Available].

PMID- 22655303
TI  - [Being a physician. . . thoughts of a woman in her fifties].

PMID- 22655304
TI  - [The Internal Medicine procedures book].

PMID- 22655305
TI  - Sampling strategies for capillary isoelectric  focusing with electroosmotic zone 
      mobilization assessed by high-resolution  dynamic computer simulation.
AB  - The impact of initial sample distribution on separation and focusing of analytes
      in a pH 3-11 gradient formed by 101 biprotic carrier ampholytes under concomitant
      electroosmotic displacement was studied by dynamic high-resolution computer
      simulation. Data obtained with application of the analytes mixed with the carrier
      ampholytes (as is customarily done), as a short zone within the initial carrier
      ampholyte zone, sandwiched between zones of carrier ampholytes, or introduced
      before or after the initial carrier ampholyte zone were compared. With sampling
      as a short zone within or adjacent to the carrier ampholytes, separation and
      focusing of analytes is shown to proceed as a cationic, anionic, or mixed process
      and separation of the analytes is predicted to be much faster than the separation
      of the carrier components. Thus, after the initial separation, analytes continue
      to separate and eventually reach their focusing locations. This is different to
      the double-peak approach to equilibrium that takes place when analytes and
      carrier ampholytes are applied as a homogenous mixture. Simulation data reveal
      that sample application between two zones of carrier ampholytes results in the
      formation of a pH gradient disturbance as the concentration of the carrier
      ampholytes within the fluid element initially occupied by the sample will be
      lower compared to the other parts of the gradient. As a consequence thereof, the
      properties of this region are sample matrix dependent, the pH gradient is
      flatter, and the region is likely to represent a conductance gap (hot spot).
      Simulation data suggest that sample placed at the anodic side or at the anodic
      end of the initial carrier ampholyte zone are the favorable configurations for
      capillary isoelectric focusing with electroosmotic zone mobilization.

PMID- 22655307
TI  - Abstracts of the 4th Joint BASHH-ASTDA Meeting. Brighton, United Kingdom. June 27
      29, 2012.

PMID- 22655306
TI  - Abstracts of the 2012 Vascular Annual Meeting. National Harbor, Maryland, USA.
      June 7-9, 2012.

PMID- 22655308
TI  - Abstracts of EUROHAND 2012, the XVIIth FESSH (Federation of the European
      Societies for Surgery of the Hand) Congress. June 20-23, 2012. Antwerp, Belgium.

PMID- 22655309
TI  - The abbreviated patient-held   record: bridging the  communication gap.

PMID- 22655310
TI  - A little 'CSI' for Health I.T.

PMID- 22655311
TI  - Sales principles to help grow lab revenues-Part I.

PMID- 22655312
TI  - Prevention.  HIV still evident in semen of men receiving HAART.

PMID- 22655313
TI  - Research.  Recent trauma affects treatment outcome for HIV-positive women.

PMID- 22655315
TI  - Female condom program shows success, cost savings.

PMID- 22655314
TI  - Research.  'Superinfected' have more potent antibody response to HIV.

PMID- 22655316
TI  - 1 in 4 HIV patients were sexually abused as children.

PMID- 22655317
TI  - Immigration. Court denies petition to review Indian man's bid for asylum.

PMID- 22655318
TI  - ADA.  Company did not discriminate against HIV-positive worker.

PMID- 22655319
TI  - Privacy Act does not authorize awards for emotional distress.

PMID- 22655320
TI  - Prison did not discriminate against HIV-positive inmates.

PMID- 22655321
TI  - ICCVAM recommends in vitro test method for endocrine-disruptors.

PMID- 22655323
TI  - Ban on the use of great apes.

PMID- 22655322
TI  - An antibody treats almost all refractory autoimmune diseases: fact and beyond.

PMID- 22655324
TI  - The ban on the use of chimpanzees in biomedical research and testing in the UK
      should be made permanent and legally binding.

PMID- 22655325
TI  - Harnessing genetic data to guide breast cancer treatment. Interviewed by Rita
      Seabra.

PMID- 22655326
TI  - Aspects of environmental contamination and associated toxicological consequences.
      Preface.

PMID- 22655327
TI  - Hypnosis.

PMID- 22655328
TI  - Cognitive hypnotherapy-twenty years later.

PMID- 22655329
TI  - Cognitive hypnotherapy: a new vision and strategy for research and practice.
AB  - This article describes cognitive hypnotherapy (CH), a visionary model of
      adjunctive hypnotherapy that advances the role of clinical hypnosis to a
      recognized integrative model of psychotherapy. As hypnosis lacks a coherent
      theory of psychotherapy and behavior change, hypnotherapy has embodied a mixed
      bag of techniques and thus hindered from transfiguring into a mainstream school
      of psychotherapy. One way of promoting the therapeutic standing of hypnotherapy
      as an adjunctive therapy is to systematically integrate it with a well
      established psychotherapy. By blending hypnotherapy with cognitive behavior
      therapy, CH offers a unified version of clinical practice that fits the
      assimilative model of integrated psychotherapy, which represents the best
      integrative psychotherapy approach for merging both theory and empirical
      findings.

PMID- 22655330
TI  - Cognitive hypnotherapy for anxiety disorders.
AB  - Cognitive hypnotherapy, also known as cognitive-behavioral hypnotherapy (CBH), is
      applied to the treatment of anxiety disorders. Specific techniques are described
      and illustrated. The research on CBH is discussed. CBH seems to be at least as
      effective as behavior therapy (BT) and cognitive-behavior therapy (CBT)
      treatments that employ imagery and relaxation techniques for anxiety disorders.
      However, more research is needed because of the lack of adequate studies
      comparing CBH with BT and CBT. Clinical implications and suggestions for future
      research are offered.

PMID- 22655331
TI  - Cognitive hypnotherapy for major depressive disorder.
AB  - Since the publication of the special issue on cognitive hypnotherapy in the
      Journal of Cognitive Psychotherapy: An International Quarterly (1994), there have
      been major developments in the application of hypnosis to the treatment of
      depression. However, there is no "one-size-fits-all" treatment for depressive
      disorders as the conditions represent a complex set of heterogeneous symptoms,
      involving multiple etiologies. It is thus important for therapists to promote a
      multimodal approach to treating depressive disorders. This article describes
      cognitive hypnotherapy (CH), an evidence-based multimodal psychological treatment
      that can be applied to a wide range of depressed patients. CH combines hypnosis
      with cognitive behavior therapy as the latter provides the best integrative
      lodestone for assimilating empirically supported treatment techniques derived
      from various psychotherapies.

PMID- 22655332
TI  - Cognitive hypnotherapy for pain management.
AB  - Pain is a serious health care problem and there is growing evidence to support
      the use of hypnosis and cognitive-behavioral interventions for pain management.
      This article reviews clinical techniques and methods of cognitive hypnotherapy
      for pain management. Current research with emphasis given to randomized,
      controlled trials is presented and the efficacy of hypnotherapy for pain
      management is discussed. Evidence for cognitive hypnotherapy in the treatment in
      chronic pain, cancer, osteoarthritis, sickle cell disease, temporomandibular
      disorder, fibromyalgia, non-cardiac chest pain, and disability related chronic
      pains are identified. Implications for clinical practice and research are
      discussed in light of the accumulating evidence in support of the efficacy and
      effectiveness of cognitive hypnotherapy for pain management.

PMID- 22655333
TI  - Post-traumatic stress disorder: cognitive hypnotherapy, mindfulness, and
      acceptance-based treatment approaches.
AB  - In this article, we describe how cognitive hypnotherapy can be used in
      conjunction with evidence-based practices for the treatment of post-traumatic
      stress disorder (PTSD). We review cognitive-behavioral interventions for PTSD,
      including mindfulness and acceptance-based approaches, and contend that (a)
      empirical support for the use of hypnosis in treating a variety of conditions is
      considerable; (b) hypnosis is fundamentally a cognitive-behavioral intervention;
      (c) psychological interventions with a firm footing in cognitive-behavioral
      therapy (CBT) are well-suited to treat the symptoms of PTSD; and (d) hypnosis can
      be a useful adjunct to evidence-based cognitive-behavioral approaches, including
      mindfulness and acceptance-based interventions, for treating PTSD.

PMID- 22655334
TI  - Cognitive behavioral hypnotherapy for dissociative disorders.
AB  - Dissociative disorders (DD) prevail as sequelae to overwhelming experiences in
      childhood. These readily formed post-traumatic responses and trance states
      develop in high hypnotizable subjects whose dysregulations become organized into
      ego states. A cognitive behavioral hypnotherapeutic treatment model will
      effectively contain, explore, metabolize, and resolve these life-endangering
      conditions. This article will detail the cognitive hypnotic world of DD patients,
      the relational spaces of the ego states, and the triphasic treatment mode to
      successfully resolve the dissociative pathology. Structured and phase appropriate
      hypnotic interventions will be described.

PMID- 22655335
TI  - Cognitive hypnotherapy with bulimia.
AB  - Research on the efficacy of hypnosis in the treatment of bulimia nervosa has
      produced mixed findings. This is due in part to the interplay between the
      characteristics of people with bulimia and the wide variety of hypnosis
      interventions that have been employed. Several authors have noted that
      methodological limitations in hypnosis research often make evaluation of
      treatment efficacy difficult. Many of the studies extant provide insufficient
      information regarding the specifics of participants' hypnotizability, the
      hypnotic induction, or the hypnotic suggestion(s) employed. Such limitations
      preclude replication and clinical implementation. This article reviews the
      literature with replicable methodologies and discusses the implications for
      evaluating treatment efficacy.

PMID- 22655336
TI  - Metaphysics for an enlightened public: The controversy over monads in Germany,
      1746-1748.
AB  - This essay analyzes the controversy that attended the prize essay question on
      monads proposed by the Berlin Academy of Sciences in 1746. The controversy was
      first touched off by an anonymous pamphlet published by the mathematician
      Leonhard Euler, the academy's most well known member, that attacked the doctrine
      of monads. It peaked with the awarding of the prize to Johann Heinrich Gottlob
      Justi, whose winning essay closely followed Euler's arguments. This essay
      discusses the controversy as one instance in a broader quarrel in the German
      academic community over the suitability of Christian Wolff's philosophy as the
      foundation for a broad range of academic disciplines, including natural
      philosophy. It also analyzes the controversy as displaying the central role of
      the periodical press in the emergent German public sphere.

PMID- 22655337
TI  - The language of objects: Christian Jurgensen Thomsen's science of the past.
AB  - The Danish amateur scholar Christian Jurgensen Thomsen has often been described
      as a founder of modern "scientific" archaeology. Thomsen's innovation, this essay
      argues, reflects developments within neighboring fields, such as philology and
      history. He reacted against historians who limited themselves to histories of
      texts and therefore abandoned the earliest human history. Instead, he proposed a
      new history of objects, which included the entire history of humankind. Thomsen's
      work as director of the Royal Museum of Nordic Antiquities in Copenhagen was
      especially important for this renewal. The arrangement of artifacts not only
      helped him formulate his theories, but also allowed him to present his arguments
      in a language of objects. At the same time, Thomsen's definition of archaeology
      as a museum science placed his branch of archaeology in a closer relationship
      with other museum sciences, such as geology and comparative anatomy. From the
      1840s, Thomsen's museum became a model for how the study of human artifacts could
      deliver scientific insights into human nature and the laws of human development.

PMID- 22655338
TI  - Senator Fred Harris's National Social Science Foundation proposal: Reconsidering
      federal science policy, natural science-social science relations, and American
      liberalism during the 1960s.
AB  - During the 1960s, a growing contingent of left-leaning voices claimed that the
      social sciences suffered mistreatment and undue constraints within the natural
      science-dominated federal science establishment. According to these critics, the
      entrenched scientific pecking order in Washington had an unreasonable commitment
      to the unity of the sciences, which reinforced unacceptable inequalities between
      the social and the natural sciences. The most important political figure who
      advanced this critique, together with a substantial legislative proposal for
      reform, was the Oklahoma Democratic Senator Fred Harris. Yet histories of science
      and social science have told us surprisingly little about Harris. Moreover,
      existing accounts of his effort to create a National Social Science Foundation
      have misunderstood crucial features of this story. This essay argues that
      Harris's NSSF proposal developed into a robust, historically unique, and
      increasingly critical liberal challenge to the post-World War II federal science
      establishment's treatment of the social sciences as "second-class citizens."

PMID- 22655339
TI  - Introduction: The secret lives of textbooks.
AB  - Textbooks have a low status in the history of science because they have been seen
      as mere repositories for scientific knowledge. But historians have recently shown
      how they play a number of roles that can illuminate different aspects of the
      history of science, from priority disputes to pedagogical practices. The essays
      in this Focus section aim to expand our vision of textbooks further by showing
      how they perform various hybrid functions in scientific development.

PMID- 22655340
TI  - Translating textbooks: Russian, German, and the language of chemistry.
AB  - Using the cases of three Russian chemistry textbooks from the 1860s--authored by
      Freidrich Beilstein, A. M. Butlerov, and D. I. Mendeleev--this essay analyzes
      their contemporary translation into German and the implications of their
      divergent histories for scholars' understanding of the processes of credit
      accrual and the choices of languages of science.

PMID- 22655341
TI  - Between training and popularization: Regulating science textbooks in secondary
      education.
AB  - Recruitment into the scientific community is one oft-stated goal of science
      education--in the post-Sputnik United States, for example--but this obscures the
      fact that science textbooks are often read by people who will never be
      scientists. It cannot be presupposed that science textbooks for younger
      audiences, students in primary and secondary schools, function in this way. For
      this reason, precollegiate-level science textbooks are sometimes discussed as a
      subset of literature popularizing science. The high school science classroom and
      the textbook are forums for exposing the public to science. The role of
      governments and educational institutions in regulating the consumption of these
      texts not only determines which books are used; it influences how they are
      written, read, and deemed authoritative. Therefore such science textbooks should
      not be seen as (at best) the disjunction of texts-for-training and books-for
      popularization. A changing sense of what "textbooks" are compels a different
      understanding of their use in the history of science.

PMID- 22655342
TI  - Playing the game: Psychology textbooks speak out about love.
AB  - Starting in 1958, Harry Harlow published numerous research papers analyzing the
      emotional and social development of rhesus monkeys. This essay examines the
      presentation of Harlow's work in introductory psychology textbooks from 1958 to
      1975, focusing on whether the textbooks erased the process of research, presented
      results without hedging, and provided a uniform account of Harlow's work and
      results. It argues that many textbooks were not passive vehicles of knowledge
      transmission; instead, they played a role similar to articles of meta-analysis
      and literature reviews.

PMID- 22655343
TI  - A tale of two textbooks: Experiments in genre.
AB  - Though the notion of a scientific textbook has been around for almost three
      centuries, the category has hardly been stable. The plasticity of the textbook
      genre may be illustrated by recent variations as well as long-term trends. In
      this brief essay I examine two idiosyncratic but highly successful physics books,
      each published in the mid 1970s, whose production, marketing, and adoption reveal
      some of the slippage between such categories as textbook, scholarly monograph,
      and popular best seller.

PMID- 22655344
TI  - Gender and politics influenced the design and interpretation of Milgram's famous
      experiment.

PMID- 22655346
TI  - A review of rapid transport of pesticides from sloping farmland to surface
      waters: processes and mitigation strategies.
AB  - Pesticides applied to sloping farmland may lead to surface water contamination
      through rapid transport processes as influenced by the complex topography and
      high spatial variability of soil properties and land use in hilly or mountainous
      regions. However, the fate of pesticides applied to sloping farmland has not been
      sufficiently elucidated. This article reviews the current understanding of
      pesticide transport from sloping farmland to surface water. It examines overland
      flow and subsurface lateral flow in areas where surface soil is underlain by
      impervious subsoil or rocks and tile drains. It stresses the importance of
      quantifying and modeling the contributions of various pathways to rapid pesticide
      loss at catchment and regional scales. Such models could be used in scenario
      studies for evaluating the effectiveness of possible mitigation strategies such
      as constructing vegetated strips, depressions, wetlands and drainage ditches, and
      implementing good agricultural practices. Field monitoring studies should also be
      conducted to calibrate and validate the transport models as well as biophysical
      economic models, to optimize mitigation measures in areas dominated by sloping
      farmland.

PMID- 22655347
TI  - Chlorobenzenes and organochlorinated pesticides in vegetable soils from an
      industrial site, China.
AB  - Organochlorinated compounds are ubiquitous contaminants in the environment,
      especially in industrial sites. The objective of the work was to investigate
      whether a vegetable field near an industrial site is safe for vegetable
      production. The residues of chlorobenzenes (CBs), hexachlorocyclohexanes (HCHs)
      and dichlorodiphenyltrichloroethanes (DDTs) in a vegetable field which was near a
      chemical plant in China were characterized. Point estimate quotient was used for
      ecological risk assessment of the investigated site. The results showed that all
      CBs except monochlorobenzene (MCB) were detected in soils. The total
      concentrations of sigmaCBs ranged from 71.06 to 716.57 ng/g, with a mean
      concentration of 434.93 ng/g. The main components of CBs in soil samples were
      dichlorobenzenes (DCBs), trichlorobenzenes (TCBs) and tetrachlorobenzenes
      (TeCBs), while for single congeners, 1,2,4-TCB had the highest concentration,
      which ranged from 13.21 to 210.35 ng/g with a mean concentration of 111.89 ng/g.
      Residues of hexachlorobenzene (HCB) in soil samples ranged from 0.9 to 11.79
      ng/g, significantly lower than sigmaDCB, sigmaTCB and sigmaTeCB. Concentrations
      of sigmaHCHs and sigmaDDTs in soils ranged from 11.32 to 55.24 ng/g and from
      195.63 to 465.58 ng/g, respectively, of which the main components were alpha-HCH
      and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE). Ecological risk assessment
      for the investigated site showed that the most potential risks were from TCBs and
      TeCBs, based on the hazard quotients. The higher residues of CBs and DDTs
      compared to the target values and the higher than 1 hazard quotients indicated
      that this area is not safe for vegetable production and thus soil remediation is
      needed.

PMID- 22655348
TI  - Responses of activities, abundances and community structures of soil denitrifiers
      to short-term mercury stress.
AB  - The responses of activities, abundances and community structures of soil
      denitrifiers to mercury (Hg) stress were investigated through a short-term
      incubation experiment. Four soil treatments with different concentrations of Hg
      (CK, Hg25, Hg50, and Hg 100, denoted as 0, 25, 50, and 100 mg Hg/kg dry soil,
      respectively) were incubated for 28 days. Soil denitrification enzyme activity
      (DEA) was measured at day 3, 7 and 28. The abundances and community structures of
      two denitrification concerning genes, nirS (cd(1)-nitrite reductase gene) and
      nosZ (nitrous oxide reductase gene), were analyzed using real-time PCR and
      denaturing gradient gel electrophoresis (DGGE). Results showed that soil DEA was
      significantly stimulated in the treatments of Hg25 and Hg50 compared with others
      at day 7. Meanwhile, no difference in the abundances of soil nirS and nosZ was
      found between Hg spiked treatments and CK, except the lower abundance of nirS (P
      < 0.05) in the Hg added treatments compared with that in the CK at day 28. The
      community structures of denitrifiers based on nirS gene presented obvious change
      at day 7 along with the Hg additions, however, no variation was found in all
      treatments based on the nosZ gene. The results indicated that Hg (Hg25 and Hg50)
      had a strongly short-term stimulation on soil DEA, and nirS gene is more
      sensitive than nosZ gene to Hg stress.

PMID- 22655349
TI  - Heavy metal phytoextraction by Sedum alfredii is affected by continual clipping
      and phosphorus fertilization amendment.
AB  - Improving the efficacy of phytoextraction is critical for its successful
      application in metal contaminated soils. Mineral nutrition affects plant growth
      and metal absorption and subsequently the accumulation of heavy metal through
      hyper-accumulator plants. This study assessed the effects of di-hydrogen
      phosphates (KH2PO4, Ca(H2PO4)2, NaH2PO4 and NH4H2PO4) application at three levels
      (22, 88 and 352 mg P/kg soil) on Sedum alfredii growth and metal uptake by three
      consecutive harvests on aged and Zn/Cd combined contaminated paddy soil. The
      addition of phosphates (P) significantly increased the amount of Zn taken up by
      S. alfredii due to increased shoot Zn concentration and dry matter yield (DMY) (P
      < 0.05). The highest phytoextraction of Zn and Cd was observed in KH2PO4 and
      NH4H2PO4 treatment at 352 mg P/kg soil. The amount of Zn removed by
      phytoextraction increased in the order of 1st clipping < 2nd clipping < 3rd
      clipping, and for Cd extraction the order was 2nd clipping < 1st clipping < 3rd
      clipping. These results indicate that the application of P fertilizers coupled
      with multiple cuttings can enhance the removal of Zn and Cd from contaminated
      soils by S. alfredii, thus shortening the time needed for accomplishing
      remediation goals.

PMID- 22655350
TI  - Effects of land use, climate, topography and soil properties on regional soil
      organic carbon and total nitrogen in the upstream watershed of Miyun Reservoir,
      North China.
AB  - Soil organic carbon (SOC) and total nitrogen (TN) contents as well as their
      relationships with site characteristics are of profound importance in assessing
      current regional, continental and global soil C and N stocks and potentials for C
      sequestration and N conservation to offset anthropogenic emissions of greenhouse
      gases. This study investigated contents and distribution of SOC and TN under
      different land uses, and the quantitative relationships between SOC or TN and
      site characteristics in the Upstream Watershed of Miyun Reservoir, North China.
      Overall, both SOC and TN contents in natural secondary forests and grasslands
      were much higher than in plantations and croplands. Land use alone explained
      37.2% and 38.4% of variations in SOC and TN contents, respectively. The optimal
      models for SOC and TN, achieved by multiple regression analysis combined with
      principal component analysis (PCA) to remove the multicollinearity among site
      variables, showed that elevation, slope, soil clay and water contents were the
      most significant factors controlling SOC and TN contents, jointly explaining
      70.3% of SOC and 67.1% of TN contents variability. Only does additional 1.9% and
      3% increase in the interpretations of SOC and TN contents variability
      respectively when land use was added to regressions, probably due to environment
      factors determine land use. Therefore, environmental variables were more
      important for SOC and TN variability than land use in the study area, and should
      be taken into consideration in properly evaluating effects of future land use
      changes on SOC and TN on a regional scale.

PMID- 22655351
TI  - Plant species coexistence alleviates the impacts of lead on Zea mays L.
AB  - Whether plant coexistence can reduce the impacts of lead (Pb) on crops in
      agroecosystems has not been well understood. We conducted a factorial experiment
      to investigate the effects of weeds coexisting with maize (Zea mays L.) on Pb
      accumulation in maize and soil microbes at two Pb levels (ambient and 300 mg/kg).
      Elevated Pb tended to increase the Pb concentration in maize and decreased soil
      microbial activity (indicated by the average well color development, AWCD),
      functional group diversity, as well as arbuscular mycorrhizal (AM) colonization
      and vesicle number of maize. Compared to the monoculture, weeds coexisting with
      maize reduced the Pb concentrations in the root, leaf, sheath and stem of maize
      at both seedling and mature stages. In maize-weed mixtures, soil microbial
      activity and functional group diversity tended to increase for both Pb treatments
      relative to the monoculture. Furthermore, principal component analysis revealed
      that the soil microbial community structure changed with the introduction of
      weeds. The highest Pb accumulation in weeds occurred for the elevated Pb
      treatment in a three species mixture. The results suggest that multiple plant
      species coexistence could reduce lead accumulation in crop plants and alleviate
      the negative impacts on soil microbes in polluted land, thereby highlighting the
      significance of plant diversity in agroecosystems.

PMID- 22655352
TI  - Uptake, translocation, and debromination of polybrominated diphenyl ethers in
      maize.
AB  - Uptake, translocation and debromination of three polybrominated diphenyl ethers
      (PBDEs), BDE-28, -47 and -99, in maize were studied in a hydroponic experiment.
      Roots took up most of the PBDEs in the culture solutions and more highly
      brominated PBDEs had a stronger uptake capability. PBDEs were detected in the
      stems and leaves of maize after exposure but rarely detected in the blank control
      plants. Furthermore, PBDE concentrations decreased from roots to stems and then
      to leaves, and a very clear decreasing gradient was found in segments upwards
      along the stem. These altogether provide substantiating evidence for the
      acropetal translocation of PBDEs in maize. More highly brominated PBDEs were
      translocated with more difficulty. Radial translocation of PBDEs from nodes to
      sheath inside maize was also observed. Both acropetal and radial translocations
      were enhanced at higher transpiration rates, suggesting that PBDE transport was
      probably driven by the transpiration stream. Debromination of PBDEs occurred in
      all parts of the maize, and debromination patterns of different parent PBDEs and
      in different parts of a plant were similar but with some differences. This study
      for the first time provides direct evidence for the acropetal translocation of
      PBDEs within plants, elucidates the process of PBDE transport and clarifies the
      debromination products of PBDEs in maize.

PMID- 22655353
TI  - Spatial distribution and pollution assessment of heavy metals in urban soils from
      southwest China.
AB  - To identify the concentrations and sources of heavy metals, and to assess soil
      environmental quality, 63 soil samples were collected in Yibin City, Sichuan
      Province, China. Mean concentrations of As, Pb, Zn, and Cu were 10.55, 61.23,
      138.88 and 56.35 mg/kg, respectively. As concentrations were comparable to
      background values, while Pb, Zn, and Cu concentrations were higher than their
      corresponding background values. Industrial areas exhibited the highest
      concentrations of As, Pb, Zn, and Cu, while the lowest concentrations occurred in
      parks. Statistical analysis was performed and two cluster groups of metals were
      identified with Pb, Zn, and Cu in one group and As in the other. Spatial
      distribution maps indicated that Pb, Zn, and Cu were mainly controlled by
      anthropogenic activities, whereas As could be mainly accounted for by soil parent
      materials. Pollution index values of As, Pb, Zn, and Cu varied in the range of
      0.24-1.93, 0.66-7.24, 0.42-4.19, and 0.62-5.25, with mean values of 0.86, 1.98,
      1.61, and 1.78, respectively. The integrated pollution index (IPI) values of
      these metals varied from 0.82 to 3.54, with a mean of 1.6 and more than 90% of
      soil samples were moderately or highly contaminated with heavy metals. The
      spatial distribution of IPI showed that newer urban areas displayed relatively
      lower heavy metal contamination in comparison with older urban areas.

PMID- 22655354
TI  - Modeling soil conservation, water conservation and their tradeoffs: a case study
      in Beijing.
AB  - Natural ecosystems provide society with important goods and services. With the
      rapid increase in human populations and excessive utilization of natural
      resources, humans frequently enhance the production of some services at the
      expense of the others. Although the need for tradeoffs between conservation and
      development is urgent, the lack of efficient methods to assess such tradeoffs has
      impeded progress. Three land use strategy scenarios (development scenario, plan
      trend scenario and conservation scenario) were created to forecast potential
      changes in ecosystem services from 2007 to 2050 in Beijing, China. GIS-based
      techniques were used to map spatial and temporal distribution and changes in
      ecosystem services for each scenario. The provision of ecosystem services
      differed spatially, with significant changes being associated with different
      scenarios. Scenario analysis of water yield (as average annual yield) and soil
      retention (as retention rate per unit area) for the period 2007 to 2050 indicated
      that the highest values for these parameters were predicted for the forest
      habitat under all three scenarios. Annual yield/retention of forest, shrub, and
      grassland ranked the highest in the conservation scenario. Total water yield and
      soil retention increased in the conservation scenario and declined dramatically
      in the other two scenarios, especially the development scenario. The conservation
      scenario was the optimal land use strategy, resulting in the highest soil
      retention and water yield. Our study suggests that the evaluation and
      visualization of ecosystem services can effectively assist in understanding the
      tradeoffs between conservation and development. Results of this study have
      implications for planning and monitoring future management of natural capital and
      ecosystem services, which can be integrated into land use decision-making.

PMID- 22655355
TI  - Sorption and cosorption of the nonionic herbicide mefenacet and heavy metals on
      soil and its components.
AB  - Sorption and cosorption of the nonionic herbicide mefenacet and two typical
      metals (copper and silver) on black soil and its components (kaolinite and humic
      acid) were investigated. It was found that because of their different valences
      and properties, Cu2+ and Ag+ presented different effects on the sorption of
      mefenacet. Due to the competition of Cu2+, along with the shells of dense water
      formed by its surface complexation, for sorption surface area with mefenacet, the
      addition of Cu2+ decreased the sorption amount of mefenacet on soil and its
      components, especially on humic acid. However, the addition of Ag+ significantly
      enhanced the sorption of mefenacet, which was attributed to the softness of the
      cation that weakened the hydrophilicity of the local region around Ag(+)
      complexed functionalities, and thus mitigated the competitive sorption of water.
      In addition, the sorption of mefenacet on soil with or without the two metals was
      generally decreased with increasing pH, which was caused by the hydrolysis of
      carbonyl and carboxyl groups on the surface of the sorbents, pi-pi interaction
      between mefenacet and the soil organic matter, and so on. On the other hand, the
      presence of mefenacet seemed to have little effect on the sorption of Cu2+ and
      Ag+, indicating that Cu2+ and Ag+ might be sorbed strongly on the tested sorbents
      and the mefenacet added was too low in concentration to affect the sorption of
      the metals.

PMID- 22655356
TI  - Leaching behavior of enrofloxacin in three different soils and the influence of a
      surfactant on its mobility.
AB  - The leaching behaviors of enrofloxacin (ENR), a fluoroquinolone group antibiotic,
      in three different standard soils, namely sandy, loamy sand and sandy loam were
      investigated according to OECD guideline 312. In addition, the effects of
      tenside, sodium dodecylbenzenesulfonate (DBS) on the mobility of ENR in two
      different soils were studied. The mobility of ENR in all three standard soils was
      very similar and was mostly (98%) concentrated on the top 0-5 cm segment of the
      soils at pH 5.7. The DBS can enhance the mobility of ENR in soils but the impact
      was in general negligible under the studied conditions.

PMID- 22655357
TI  - Bacterial reduction and release of adsorbed arsenate on Fe(III)-, Al- and
      coprecipitated Fe(III)/Al-hydroxides.
AB  - Mobilization of arsenic under anaerobic conditions is of great concern in arsenic
      contaminated soils and sediments. Bacterial reduction of As(V) and Fe(II)
      influences the cycling and partitioning of arsenic between solid and aqueous
      phase. We investigated the impact of bacterially mediated reductions of
      Fe(III)/Al hydroxides-bound arsenic(V) and iron(III) oxides on arsenic release.
      Our results suggested that As(V) reduction occurred prior to Fe(III) reduction,
      and Fe(III) reduction did not enhance the release of arsenic. Instead, Fe(III)
      hydroxides retained their dissolved concentrations during the experimental
      process, even though the new iron mineral-magnetite formed. In contrast, the
      release of reduced As(III) was promoted greatly when aluminum hydroxides was
      incorporated. Thus, the substitution of aluminum hydroxides may be responsible
      for the release of arsenic in the contaminated soils and sediments, since
      aluminum substitution of Fe(III) hydroxides universally occurs under natural
      conditions.

PMID- 22655358
TI  - Hydrothermal fabrication and visible-light-driven photocatalytic properties of
      bismuth vanadate with multiple morphologies and/or porous structures for methyl
      orange degradation.
AB  - Monoclinic BiVO4 with multiple morphologies and/or porous structures were
      fabricated using the hydrothermal strategy. The materials were characterized by
      means of the XRD, Raman, TGA/DSC, SEM, XPS, and UV-Vis techniques. The
      photocatalytic activities of the BiVO4 materials were evaluated for the
      degradation of Methyl Orange under visible-light irradiation. It is observed that
      pH value and surfactant exerted a great effect on the morphology and pore
      structure of the BiVO4 product. Spherical BiVO4 with porous structures, flower
      cluster-like BiVO4, and flower-bundle-like BiVO4 were generated hydrothermally at
      100 degrees C with poly(vinyl pyrrolidone) (PVP) and urea (pH = 2) and at 160
      degrees C with NaHCO3 (pH = 7 and 8), respectively. The PVP-derived BiVO4 showed
      much higher surface areas (5.0-8.4 m2/g) and narrower bandgap energies (2.45-2.49
      eV). The best photocatalytic performance of the spherical BiVO4 material with a
      surface area of 8.4 m2/g was associated with its higher surface area, narrower
      bandgap energy, higher surface oxygen vacancy density, and unique porous
      architecture.

PMID- 22655359
TI  - Effects of tungsten oxide on the activity and thermal stability of a sulfate
      derived titania supported platinum catalyst for propane oxidation.
AB  - A Pt/WO3/TiO2 catalyst for propane oxidation was prepared by a stepwise wet
      impregnation method, and was aged at 800 degrees C for 5 hr. Compared to the
      sulfate-derived titania supported catalyst, the introduction of tungsten oxide as
      stable Bronsted acid sites led to the formation of more metallic platinum active
      sites at the Pt/WO3 interface. The dissociation of surface intermediates for
      propane oxidation was promoted on the WO3-modified catalyst. This, as well as the
      inhibition effects of tungsten oxide on the sintering of anatase and the phase
      transformation to rutile, resulting in a high activity and thermal stability for
      the Pt/WO3/TiO2 catalyst.

PMID- 22655360
TI  - Rubber sheet strewn with TiO2 particles: photocatalytic activity and
      recyclability.
AB  - A new method for the preparation of rubber sheet strewn with titanium dioxide
      particles (TiO2-strewn sheet) is presented. This simple and low cost method is
      based on the use of TiO2 powder (Degussa P25) being strewn onto the sheet made
      from rubber latex (60% HA) through a steel sieve. The characteristic of the TiO2
      strewn sheet was studied by using scanning electron microscopy/energy dispersive
      X-ray spectrometer (SEM/EDS) and X-ray diffractometer (XRD) techniques. The
      photocatalytic activity of TiO2-strewn rubber sheet was evaluated using Indigo
      Carmine (IC) dye as a model for organic dye pollutant in water. The results
      showed that the TiO2-strewn sheet could degrade IC dye solution under UV light
      irradiation. The effects of pH, initial concentration, and the intensity of UV
      light on the photodegradation were also investigated. Kinetics of the
      photocatalytic degradation was of the first-order reaction. The used TiO2-strewn
      sheet can be recovered and reused. The recycling uses did not require any
      cleaning between successive uses and no decline in the photodegradation
      efficiency was observed compared with freshly prepared TiO2-strewn sheet.

PMID- 22655361
TI  - Glucose production from hydrolysis of cellulose over a novel silica catalyst
      under hydrothermal conditions.
AB  - A novel silica catalyst was synthesized by evaporation-induced self-assembly
      (EISA) method and tested for the catalytic selective hydrolysis of cellulose to
      glucose. This silica catalyst exhibited a higher catalytic activity than other
      oxides prepared by the same method, such as ZrO2, TiO2, and Al2O3. Using silica
      as a catalyst, cellulose was selectively hydrolyzed into glucose with a glucose
      yield as high as 50% under hydrothermal conditions without hydrogen gas. The
      silica catalyst was characterized by Brunauer-Emmett-Teller (BET), X-ray
      diffraction (XRD) and transmission electron microscopy (TEM). The results of
      temperature-programmed desorption of ammonia (NH3-TPD) and textural properties
      indicated that the synergistic effect between strong acidity and a suitable pore
      diameter of the silica catalyst may be responsible for its high activity. In
      addition, the catalyst was recyclable and showed excellent stability during the
      recycle catalytic runs.

PMID- 22655362
TI  - Photocatalytic degradation of 4-chlorophenol under P-modified TiO2/UV system:
      kinetics, intermediates, phytotoxicity and acute toxicity.
AB  - A series of phosphorus-modified titanium dioxide samples with varying P/Ti atomic
      ratio were conveniently prepared via a conventional solgel route. The effects of
      phosphorus content and calcination temperature on the crystalline structure,
      grain growth, surface area, and the photocatalytic activity of P-modified TiO2
      were investigated. The XRD results showed that P species slow down the particle
      growth of anatase and increase the anatase-to-rutile phase transformation
      temperature to more than 900 degrees C. Kinetic studies on the P-modified TiO2 to
      degraded 4-chlorophenol had found that the TP5(500) prepared by adopting a P/Ti
      atomic ratio equal to 0.05 and calcined at 500 degrees C had an apparent rate
      constant equal to 0.0075 min(-1), which is superior to the performance of a
      commercial photocatalyst Degussa P25 K(app) = 0.0045 min(-1) and of unmodified
      TiO2 (TP0(500)) K(app) = 0.0022 min(-1). From HPLC analyses, various hydroxylated
      intermediates formed during oxidation had been identified, including hydroquinone
      (HQ), benzoquinone (BQ) and (4CC) 4-chlorocatechol as main products.
      Phytotoxicity was assessed before and after irradiation against seed germination
      of tomato (Lycopersicon esculentum) whereas acute toxicity was assessed by using
      Folsomia candida as the test organism. Intermediates products were all less toxic
      than 4-chlorophenol and a significant removal of the overall toxicity was
      accomplished.

PMID- 22655363
TI  - Novel Co-Mg-Al-Ti-O catalyst derived from hydrotalcite-like compound for NO
      storage/decomposition.
AB  - Catalysts of Co1.5Mg1.5/Al0.9Ti0.1O and Co1.5Mg1.5/A1O were successfully prepared
      by calcinations of corresponding hydrotalcite-like compounds at 800 degrees C for
      4 hr. The derived oxides were of spinel phase and a small quantity of Ti
      substitution did not change the crystal purity. Their catalytic performance for
      the NO storage/decomposition was investigated. Ti incorporation enhanced the NO
      decomposition activity while has an opposite effect on the storage capacity of
      catalyst. In situ FT-IR spectra of the catalysts showed that the final adsorption
      species on the catalysts was coordinated nitrates/nitrites. In addition, NO
      storage/decomposition mechanism has been discussed on the basis of these
      observations.

PMID- 22655364
TI  - Vaporization reduction characteristics of aqueous ammonia solutions by the
      addition of ethylene glycol, glycerol and glycine to the CO2 absorption process.
AB  - Aqueous ammonia (NH3) solution can be used as an alternative absorption for the
      control of CO2 emitted from flue gases due to its high absorption capacity, fast
      absorption rate and low corrosion problem. The emission of CO2 from iron and
      steel plants requires much attention, as they are higher than those emitted from
      power plants at a single point source. In the present work, low concentration
      ammonia liquor, 9 wt.%, was used with various additives to obtain the kinetic
      properties using the blast furnace gas model. Although a solution with a high
      ammonia concentration enables high CO2 absorption efficiency, ammonium ions are
      lost as ammonia vapor, resulting in reduced CO2 absorption due to the lower
      concentration of the ammonia absorbent. To decrease the vaporization of ammonia,
      ethylene glycol, glycerol and glycine, which contain more than one hydroxyl
      radical, were chosen. The experiments were conducted at 313 K similar to the CO2
      absorption conditions for the blast furnace gas model.

PMID- 22655365
TI  - Mn-CeOx/Ti-PILCs for selective catalytic reduction of NO with NH3 at low
      temperature.
AB  - Titanium-pillared clays (Ti-PILCs) were obtained by different ways from TiCl4,
      Ti(OC3H7)4 and TiOSO4, respectively. Mn-CeO(x)/)Ti-PILCs were then prepared and
      their activities of selective catalytic reduction (SCR) of NO with NH3 at low
      temperature were evaluated. Mn-CeO(x)/Ti-PILCs were characterized by X-ray
      diffraction, N2 adsorption, Fourier transform infrared spectroscopy, thermal
      analysis, temperature-programmed desorption of ammonia and H2-temperature
      programmed reduction. It was found that Ti-pillar tend to be helpful for the
      enlargement of surface area, pore volume, acidity and the enhancement of thermal
      stability for Mn-CeO(x)/Ti-PILCs. Mn-CeO(x)/Ti-PILCs catalysts were active for
      the SCR of NO. Among three resultant Mn-CeO(x)/Ti-PILCs, the catalyst from TiOSO4
      showed the highest activity with 98% NO conversion at 220 degrees C, it also
      exhibited good resistance to H2O and SO2 in flue gas. The catalyst from TiCl4
      exhibited the lowest activity due to the unsuccessful pillaring process.

PMID- 22655366
TI  - Effects of Ce on catalytic combustion of methane over Pd-Pt/Al2O3 catalyst.
AB  - Activity and stability of 1%Pd-0.2%Pt/Al2O3 and 1%Pd-0.2%Pt/0.6%Ce/Al2O3
      catalysts prepared by impregnation method for catalytic combustion of methane in
      air were investigated. The catalysts before and after reaction were characterized
      by BET, CO chemisorption, XRD and XP S techniques. Results showed that the
      presence of Ce significantly increased the activity and thermal stability of the
      Pd-Pt/Al2O3 catalyst towards methane combustion, which could be attributed to
      more highly-dispersed active PdO particles over the Pd-Pt/Ce/Al2O3 catalyst
      surface as well as the retarded sintering of PdO and the maintained oxidized
      state of surface Pd during the combustion process in the presence of Ce.

PMID- 22655367
TI  - Sulfide oxidation in fluidized bed bioreactor using nylon support material.
AB  - A continuous fluidized bed bioreactor (FBBR) with nylon support particles was
      used to treat synthetic sulfide wastewater at different hydraulic retention time
      of 25, 50 and 75 min and upflow velocity of 14, 17 and 20 m/hr. The effects of
      upflow velocity, hydraulic retention time and reactor operation time on sulfide
      oxidation rate were studied using statistical model. Mixed culture obtained from
      the activated sludge, taken from tannery effluent treatment plant, was used as a
      source for microorganisms. The diameter and density of the nylon particles were 2
      3 mm and 1140 kg/m3, respectively. Experiments were carried out in the reactor at
      a temperature of (30 +/- 2) degrees C, at a fixed bed height of 16 cm after the
      formation of biofilm on the surface of support particles. Biofilm thickness
      reached (42 +/- 3) microm after 15 days from reactor start-up. The sulfide
      oxidation, sulfate and sulfur formation is examined at all hydraulic retention
      times and upflow velocities. The results indicated that almost 90%-92% sulfide
      oxidation was achieved at all hydraulic retention times. Statistical model could
      explain 94% of the variability and analysis of variance showed that upflow
      velocity and hydraulic retention time slightly affected the sulfide oxidation
      rate. The highest sulfide oxidation of 92% with 70% sulfur was obtained at
      hydraulic retention time of 75 min and upflow velocity of 14 m/hr.

PMID- 22655368
TI  - Comparison of dynamic adsorption/desorption characteristics of toluene on
      different porous materials.
AB  - Four different types of adsorbents, SBA-15, MCM-41, NaY and SiO2, were used to
      study the dynamic adsorption/desorption of toluene. To further investigate the
      influence of pore structure on its adsorption performance, two SBA-15 samples
      with different microspores were also selected. It is shown that microporous
      material NaY has the largest adsorption capacity of 0.2873 mL/g, and the
      amorphous SiO2 exhibits the least capacity of 0.1003 mL/g. MCM-41 also shows a
      lower break through capacity in spite of the relatively small pore diameter,
      because it can not provide the necessary small geometric confinement for the tiny
      adsorbates. However, the mesoporous SBA-15 silica with certain micropore volume
      shows relatively higher adsorption capacity than that of MCM-41 silica. The
      presence of micropores directly leads to an increase in the dynamic adsorption
      capacity of toluene. Although NaY has the highest adsorption capacity for
      toluene, its complete desorption temperature for toluene is high (> 350 degrees
      C), which limits its wide application. On the contrary, mesoporous silica
      materials exhibits a good desorption performance for volatile organic compounds
      at lower temperatures. Among these materials mesoporous SBA-15 samples, with a
      larger amount micropores and a lower desorption temperature, are a potentially
      interesting adsorbent for the removal of volatile organic compounds. This
      behavior should been related with the best synergetic effect of mesopores and
      micropores.

PMID- 22655369
TI  - Solar active fire clay based hetero-Fenton catalyst over a wide pH range for
      degradation of Acid Violet 7.
AB  - Fe(III) immobilized fire clay (Fe-FC) was prepared using ferric nitrate by solid
      state dispersion method and this hetero-Fenton catalyst was applied for the
      degradation of Acid Violet 7 (AV 7) under natural sunlight. The 26% ferric
      nitrate loaded fire clay was found to be most efficient. The experimental
      conditions such as solution pH, H2O2 concentration for efficient degradation of
      AV 7 have been determined. Unlike Fenton catalyst, Fe-FC is photoactive over a
      wide pH range of 3-7. This catalyst was found to be stable and reusable. The GC
      MS analysis of experimental solutions during irradiation revealed the formation
      of 2,8-diaminonaphthalene-1,3,6-triol, 8-aminonaphthalene-1,2,3,6-tetrol, 2
      aminonaphthalene-1,3,6,8-tetrol and 2-aminobenzene-1,3-diol/5-aminonbenzene-1,3
      diol/ 2-aminobenzene-1,4-diol as intermediates. The 26% ferric nitrate loaded
      fire clay was characterized by XRD, ICP-AES, BET surface area, FT-IR, SEM-EDS and
      UV-DRS studies.

PMID- 22655370
TI  - Study of DDT and its derivatives DDD, DDE adsorption and degradation over Fe-SBA
      15 at low temperature.
AB  - Mesoporous SBA-15 with different Fe2O3 loading were synthesized by an in-situ
      coating progress for removals of dichlorodiphenyltrichloroethane (DDT) and its
      derivatives, i.e., 1,1-dichloro-2,2-bis-(p-chlorophenyl)ethane (DDD) and 1,1
      dichloro-2,2-bis-(4-chloro -phenyl) ethane (DDE). The results from XRD (X-ray
      diffractometer), TEM (transmission electron microscopy) indicated that the iron
      could be well dispersed on SBA-15 within 6 wt.% Fe2O3 loading. Nitrogen
      adsorption-desorption tests indicated that the synthesized materials were
      characterized by ordered meso-structure, high surface area and large pore volume.
      DDTs were removed from aqueous media in 12-hr treatment and high removal
      efficiency of DDTs was achieved at over 94%. DDTs could be completely degraded at
      350 degrees C under the existence of SBA-15 with 4 wt.% Fe2O3 loading. The final
      degradation products of DDT were dichlorobenzophenone (DCB) and bis-(4-chloro
      phenyl) methane (DDM), suggesting a complete dechlorination from trichloromethyl.

PMID- 22655371
TI  - An E. coli SOS-EGFP biosensor for fast and sensitive detection of DNA damaging
      agents.
AB  - An E. coli SOS-EGFP biosensor which expresses enhanced green fluorescent protein
      as a reporter protein under the control of recA gene promoter in SOS response was
      constructed for detection of DNA damage and evaluation of DNA damaging chemicals.
      The chemicals that may cause substantial DNA damage will trigger SOS response in
      the constructed bacterial biosensor, and then the reporter egfp gene under the
      control of recA promoter is stimulated to express as a fluorescent protein,
      allowing fast and sensitive fluorescence detection. Interestingly, this biosensor
      can be simultaneously applied for evaluation of genotoxicity and cytotoxicity.
      The SOS-EGFP bacterial biosensor provides a sensitive, specific and simple method
      for detecting known and potential DNA damaging chemicals.

PMID- 22655372
TI  - Self-catalytic degradation of ortho-chlorophenol with Fenton's reagent studied by
      chemiluminescence.
AB  - The degradation of ortho-chlorophenol using Fenton's reagent was studied by
      chemiluminescence (CL). Without a special CL reagent, a weak CL emission from the
      mixture of ferrous ion and hydrogen peroxide was observed at room temperature.
      The CL intensity was increased by the addition of ortho-chlorophenol into the
      mixed solution. When the temperature was raised to 65 degrees C, the CL intensity
      was enhanced strongly. The CL mechanisms for the system H2O2-Fe2+ with and
      without ortho-chlorophenol were studied by examining the CL spectrum, gas
      chromatography-mass spectrometry and electron spin resonance spectrum. The
      effects of various free radical scavengers, surfactants and fluorescence
      compounds on the CL intensity were also investigated. A self-catalytic oxidation
      mechanism was proposed. The results showed that singlet oxygen was the main
      emitter for the system H2O2-Fe2+. The strong CL from the system H2O2-Fe(2+)-ortho
      chlorophenol was due to singlet oxygen and electronically excited quinone. The
      benzenediol-like intermediate product formed during the phenol oxidation process
      greatly promoted the Fenton's reaction and led to higher CL intensity.
      Chemiluninescence is a novel approach for the investigation of the oxidation of
      some organic pollutants by Fenton's reagent.

PMID- 22655373
TI  - Concentrations and sources of an emerging pollutant, decabromodiphenylethane
      (DBDPE), in sewage sludge for land application.
AB  - The presence of an emerging brominated flame retardant, decabromodiphenylethane
      (DBDPE), has been confirmed in Spanish sewage sludge. Thirty one samples from
      different urban wastewater treatment plants (WWTPs) were analyzed for this
      brominated flame retardant. DBDPE was positively identified and quantified in all
      samples at lower concentrations (47.0 +/- 29.7 ng/g dry weight (dw); mean +/- SD)
      than those obtained for decabromodiphenyl ether (BDE-209) (290 +/- 236 ng/g dw;
      mean +/- SD) in a previous study. Influence of the WWTP characteristics in the
      pollutant levels was evaluated. No significant correlations were obtained between
      DBDPE concentrations and the population or sewage sludge production rate
      associated with the plants, neither wastewater treatment method. Sources of DBDPE
      in the sludge were also evaluated. Data indicate a common origin for DBDPE and
      BDE-209, which may be related to leaching processes during the use and disposal
      of consumer products containing these chemicals. Nevertheless, DBDPE contents are
      not influenced by industrial activities, which suggests that the infusion of
      DBDPE commercial mixture is not a source of this chemical into the environment,
      and indicates that the use of DBDPE in the Spanish industry is still low compared
      to deca-BDE.

PMID- 22655374
TI  - Determination of ammonium on an integrated microchip with LED-induced
      fluorescence detection.
AB  - A simply fabricated microfluidic device integrated with a fluorescence detection
      system has been developed for on-line determination of ammonium in aqueous
      samples. A 365-nm light-emitting diode (LED) as an excitation source and a minor
      band pass filter were mounted into a polydimethylsiloxane (PDMS)-based microchip
      for the purpose of miniaturization of the entire analytical system. The ammonium
      sample reacted with o-phthaldialdehyde (OPA) on-chip with sodium sulfite as
      reducing reagent to produce a fluorescent isoindole derivative, which can emit
      fluorescence signal at about 425 nm when excited at 365 nm. Effects of pH, flow
      rate of solutions, concentrations of OPA-reagent, phosphate and sulfite salt were
      investigated. The calibration curve of ammonium in the range of 0.018-1.8
      microg/mL showed a good linear relationship with R2 = 0.9985, and the detection
      limit was (S/N = 3) 3.6 x 10(-4) microg/mL. The relative standard deviation was
      2.8% (n = 11) by calculating at 0.18 microg/mL ammonium for repeated detection.
      The system was applied to determine the ammonium concentration in rain and river
      waters, even extent to other analytes fluorescence detection by the presented
      device.

PMID- 22655375
TI  - A review of polybrominated diphenyl ethers and alternative brominated flame
      retardants in wildlife from China: levels, trends, and bioaccumulation
      characteristics.
AB  - Accelerated industrialization and urbanization, and unregulated disposal of waste
      of electric and electronic equipment (e-waste) in China have caused environmental
      pollution of brominated flame retardants (BFRs). This review summarized the
      levels, trends, and bioaccumulation characteristics of polybrominated diphenyl
      ethers (PBDEs) and other potential alternative BFRs including
      hexabromocyclododecanes (HBCDs), 1,2-bis(2,4,6-dibromophenoxy) ethane (BTBPE) and
      decabromodiphenylethane (DBDPE) in wildlife from China. PBDE levels in wildlife
      from China were generally higher than those from other parts in Asia, and were
      comparable to those from Europe but were lower than those from North America.
      However, wildlife from the e-waste recycling sites in South China and East China
      contained much higher PBDEs compared to other reports around the world,
      suggesting the heavy contamination of PBDEs in these regions. The alternative
      BFRs were also detected in wildlife, revealing that the animals are exposed to
      these chemicals, in addition to PBDEs. Temporal trends indicated by levels in
      marine mammals from South China suggested that PBDE levels increased from the
      beginning of 1990s to 2000s, but decreased from the middle of 2000s, followed by
      relatively steady levels. In contrast, HBCDs were found to be continuously
      increasing from 1997 to 2007, indicating the increasing usage of HBCDs in China
      in recent years. Compared to PBDE profiles found in other parts, aquatic species
      and birds from China contained relatively higher contributions of BDE-28 and 209,
      respectively, suggesting the possible different usage pattern of PBDEs. Future
      works including keeping monitoring at a reasonable scale and frequency to make
      sure levels near urban centers indicative of population do not increase are
      needed. Additionally, focus effort on e-waste recycling regions to look for
      impacts and to determine if regulation/controls are resulting in lower
      environmental contamination, and incorporation of sentinel species in monitoring
      efforts are recommended.

PMID- 22655376
TI  - Histological observation on unique phenotypes of malformation induced in Xenopus
      tropicalis larvae by tributyltin.
AB  - Tributyltin (TBT), a biocide used in antifouling paints, has shown strong
      teratogenic effects on Xenopus tropicalis embryos at environmentally relevant
      concentrations. X. tropicalis embryos were exposed to 50, 100 and 200 ng/L
      tributyltin chloride for 72 hr. The histological changes were further observed on
      abnormal eyes, enlarged trunks, enlarged proctodaeums and absence of fins induced
      by TBT. The lens and the retinal layers of abnormal eyes were slightly or barely
      differentiated, and that the pigment epithelium was neither continuous nor
      smooth. The abdomens were full of undifferentiated gut tissue with yolk-rich
      inclusions in the tadpoles with enlarged trunks. The proctodaeums formed a bump
      like or columnar structure. The mass of yolk-rich cells occupied the lumen,
      blocked the opening and even turned inside out of the proctodaeum. Both the
      ventral and dorsal fins in trunks and tails became narrow or even disappeared
      totally. Our results suggest that great changes of histology took place
      corresponding to the unique phenotypes. The gut tissue was poorly differentiated,
      which led to the failed elongation of the guts and subsequently the enlarged
      trunks. The enlarged proctodaeums were due to the undifferentiation of inner
      layer, the expansion of outer epidermal part and the absence of fins around them.
      In brief, the histological observations provided insights into the reason of the
      unique external malformations in some degree.

PMID- 22655377
TI  - Atrazine accumulation and toxic responses in maize Zea mays.
AB  - Atrazine accumulation, oxidative stress, and defense response in maize seedlings
      exposed to extraneous atrazine were studied. Accumulation of atrazine in maize
      increased with increasing exposure concentration. The abscisic acid (ABA) content
      was positively correlated with the atrazine concentrations in maize roots and
      shoots (p < 0.05). Hydroxyl radical (*OH) in maize was determined in vivo with
      electron paramagnetic resonance spectroscopy. Its intensity was positively
      correlated with atrazine concentration in roots and shoots (p < 0.05), and higher
      level of *OH generated in roots than in shoots corresponded to the major
      accumulation of atrazine in roots. Superoxide dismutase, peroxidase and catalase
      in roots were up-regulated by atrazine exposure at 1 mg/L compared to the control
      and malondialdehyde content in roots was enhanced when atrazine exposure
      concentration reached 10 mg/L. These results suggested the exposure and
      accumulation of atrazine caused oxidative toxicity and antioxidant response in
      maize.

PMID- 22655378
TI  - Effects of rare earth elements La and Yb on the morphological and functional
      development of zebrafish embryos.
AB  - In recent years, with the wide applications and mineral exploitation of rare
      earth elements, their potential environmental and health effects have caused
      increasing public concern. Effect of rare earth elements La and Yb on the
      morphological and functional development of zebrafish embryos were studied. The
      embryos were exposed to La3+ or Yb3+ at 0, 0.01, 0.1, 0.3, 0.5 and 1.0 mmol/L,
      respectively. Early life stage parameters such as egg and embryo mortality,
      gastrula development, tail detachment, eyes, somite formation, circulatory
      system, pigmentation, malformations, hatching rate, length of larvae and
      mortality were investigated. The results showed La3+ and Yb3+ delayed zebrafish
      embryo and larval development, decreased survival and hatching rates, and caused
      tail malformation in a concentration-dependent way. Moreover, heavy rare-earth
      ytterbium led to more severe acute toxicity of zebrafish embryo than light rare
      earth lanthanum.

PMID- 22655379
TI  - Mineral nutrient imbalance, DNA lesion and DNA-protein crosslink involved in
      growth retardation of Vicia faba L. seedlings exposed to lanthanum ions.
AB  - Effects of mineral nutrient imbalance, DNA lesion and DNA-protein crosslink on
      growth of Vicia faba L. seedlings hydroponically cultivated in concentrations of
      extraneous lanthanum (La) for 20 days were investigated in the present
      experiment. The results showed that contents of La, Cu or K elements in roots
      generally changed synchronously with those in leaves, while Ca, Fe, Zn, Mg, Mn or
      P in the roots altered inversely to those in the leaves. Thus, the extraneous La
      led to redistribution and imbalance of mineral nutrient elements in the roots and
      leaves. DNA lesion and DNA-protein crosslink were investigated by single cell gel
      electrophoresis (SCGE) and sodium dodecyl sulfate/potassium (SDS/K+)
      precipitation methods, respectively. The results demonstrated that the increasing
      La induced DNA break and DNA-protein crosslinks (DPCs) in the seedlings. These
      results suggested that mineral nutrient imbalance, DNA lesion and DNA-protein
      crosslink were involved in the growth retardation and growth alteration of the
      seedlings, which may help to understand the mechanisms of rare earth elements
      (REEs) on plant growth.

PMID- 22655380
TI  - Polybrominated diphenyl ether levels in wild and farmed Chilean salmon and
      preliminary flow data for commercial transport.
AB  - This pilot study documented the occurrence and levels of brominated flame
      retardants in the tissues of farmed and wild salmon in southern Chile. Samples of
      Coho salmon and rainbow trout were obtained from fish farms, rivers and lakes in
      the Patagonia in Aysen Region, Chile. The samples were analyzed by Gas
      Chromatography Negative Chemical Ionization Mass Spectrometry for the different
      polybrominated diphenyl ether (PBDE) congeners. Contaminants were observed in all
      the samples, and the congeners BDE 17, 28, 47 and 66 were observed in all both
      farmed and wild samples. The concentrations were higher in the farmed Coho
      salmon, presenting significant differences with wild salmon. The levels reached
      182 pg/g wet weight (ww) vs. 120 ww. In the case of the rainbow trout, the
      concentrations were lower, although the congener profile was quite similar. The
      levels reached an average of 100 pg/g ww in the farmed fish versus 110 pg/g ww in
      wild fish, and no significant difference was observed between the species. In
      both species, the congener with the highest concentration was BDE 47. Based on
      this information, the BDE flow was estimated for commerce, which is a form of
      pollutant transport not usually considered in POP pollution studies. A
      preliminary estimation indicated that the quantity of PBDEs mobilized by commerce
      was in the order of kg, and in the case of Chile might reach almost 1 kg.

PMID- 22655381
TI  - Degradation behavior of 17alpha-ethinylestradiol by ozonation in the synthetic
      secondary effluent.
AB  - Endocrine disrupting chemicals (EDCs) in the secondary effluent discharged from
      wastewater treatment plants (WWTPs) are of great concern in the process of water
      reuse. Ozonation has been reported as a powerful oxidation technology to
      eliminate micropollutants in water treatment. Due to the complexity of the
      wastewater matrix, orthogonal experiments and single factor experiments were
      conducted to study the influence of operational parameters on the degradation of
      17a-ethinylestradiol (EE2) in the synthetic secondary effluent. The results of
      the orthogonal experiments indicated that the initial ozone and natural organic
      matter (NOM) concentration significantly affected EE2 degradation efficiency,
      which was further validated by the single factor confirmation experiments. EE2
      was shown to be effectively degraded by ozonation in the conditions of low pH
      (6), NOM (10 mg/L), carbonate (50 mg/L), but high suspended solid (20 mg/L) and
      initial ozone concentration (9 mg/L). The study firstly revealed that the lower
      pH resulted in higher degradation of EE2 in the synthetic secondary effluent,
      which differed from EDCs ozonation behavior in pure water. EE2 degradation by
      ozone molecule instead of hydroxyl radical was proposed to play a key role in the
      degradation of EDCs by ozonation in the secondary effluent. The ratio between 03
      and TOC was identified as an appropriate index to assess the degradation of EE2
      by ozonation in the synthetic secondary effluent.

PMID- 22655382
TI  - Effect of wastewater COD/N ratio on aerobic nitrifying sludge granulation and
      microbial population shift.
AB  - The effect of COD/N ratio on the granulation process and microbial population
      succession was investigated. Four identical sequencing batch reactors, R1, R2, R3
      and R4, were operated with various initial COD/N ratios ranging from 0/200 to
      800/200 (m/m). Ethanol was fed as the source of COD. Aerobic granules were
      successfully cultivated in R2 and R3, operating with the COD/N ratio of 200/200
      and 400/200, respectively. Scanning electron microscope observations indicated
      that short rod-shaped and spherical bacteria were dominant in R2, while granules
      produced in R3 were surrounded with a large amount of filamentous bacteria. The
      average specific nitritation rate in R2 and R3 were 0.019 and 0.008 mg N/(mg
      MLVSS x hr), respectively. Fluorescence in situ hybridization results
      demonstrated that nitrifying bacteria population was enriched remarkably in R2.
      It indicated that nitrification ability and nitrifying bacteria population were
      enriched remarkably at low COD/N ratio. However, no granules were formed in R1
      and R4 which might attribute to either limited or excessive extracellular
      polymeric substances production. This study contributed to a better understanding
      of the role of COD/N ratio in nitrifying sludge granulation.

PMID- 22655383
TI  - Removal of tetracycline from water by Fe-Mn binary oxide.
AB  - Significant concerns have been raised over the presence of antibiotics including
      tetracyclines in aquatic environments. A series of Fe-Mn binary oxide with
      different Fe:Mn molar ratios was synthesized by a simultaneous oxidation and
      coprecipitation process for TC removal. Results showed that Fe-Mn binary oxide
      had higher removal efficiency than that of hydrous iron oxide and hydrous
      manganese oxide, and that the oxide with a Fe:Mn molar ratio of 5:1 was the best
      in removal than other molar ratios. The tetracycline removal was highly pH
      dependent. The removal of tetracycline decreased with the increase of initial
      concentration, but the absolute removal quantity was more at high concentration.
      The presence of cations and anions such as Ca2+, Mg2+, CO3(2-) and SO4(2-) had no
      significant effect on the tetracycline removal in our experimental conditions,
      while SiO3(2-) and PO4(3-) had hindered the adsorption of tetracycline. The
      mechanism investigation found that tetracycline removal was mainly achieved by
      the replacement of surface hydroxyl groups by the tetracycline species and
      formation of surface complexes at the water/oxide interface. This primary study
      suggests that Fe-Mn binary oxide with a proper Fe:Mn molar ratio will be a very
      promising material for the removal of tetracycline from aqueous solutions.

PMID- 22655384
TI  - Removal of polycyclic aromatic hydrocarbons and phenols from coking wastewater by
      simultaneously synthesized organobentonite in a one-step process.
AB  - The optimal condition for a one-step process removing organic compounds from
      coking wastewater by simultaneously synthesized organobentonite as a pretreatment
      was investigated. Results showed that sorption of organic compounds by
      organobentonite was positively correlated to the cation surfactant exchange on
      the bentonite and the octanol-water partition coefficient (Kow) of the solutes.
      With 0.75 g/L bentonite and 180 mg/L (60% of bentonite cation exchange capacity)
      cetyltrimethylammonium bromide, the removal efficiencies of the 16 polycyclic
      aromatic hydrocarbon (PAHs) specified by the US Environmental Protection Agency
      in coking wastewater except naphthalene were more than 90%, and that of
      benzo(a)pyrene was 99.5%. At the same time, the removal efficiencies of COD(Cr),
      NH3-N, volatile phenols, colour and turbidity were 28.6%, 13.2%, 8.9%, 55% and
      84.3%, respectively, and the ratio of BOD5/COD(Cr) increased from 0.31 to 0.41.
      These results indicated that the one-step process had high removal efficiency for
      toxic and refractory hydrophobic organic compounds, and could improve the
      biodegradability of the coking wastewater. Therefore it could be a promising
      technology for the pretreatment of toxic and refractory organic wastewater.

PMID- 22655385
TI  - Photolysis of chlortetracycline in aqueous solution: kinetics, toxicity and
      products.
AB  - The aqueous photodegradation of the widely used antibiotic chlortetracycline
      (CTC) was investigated under simulated sunlight. The quantum yield of
      photodegradation increased from 3.3 x 10(-4) to 8.5 x 10(-3) within the pH range
      of 6.0 to 9.0. The presence of Ca2+, Fe3+, and NO(-3) enhanced the
      photodegradation of CTC, whereas Mg2+, Mn2+, and Zn2+ inhibited the degradation
      with the order Mn2+ > Zn2+ > Mg2+ at pH 7.3. The monovalent cations (Na+ and K+)
      had negligible effect on the photolysis of CTC. Fulvic acid (FA) decreased the
      photodegradation of CTC due to light screening effect. Hydrogen peroxide (H2O2)
      was formed concurrently with direct photodegradation of CTC. The generation rate
      of H2O2 increased from 0.027 to 0.086 micromol/(L x min) when the pH ranged from
      6.0 to 9.0. The CTC solution was about three-fold more toxic to the
      Photobacterium phosphoreum bacteria after irradiation, suggesting that the
      photoproducts and H2O2 formed in the CTC solution exhibited high risk on the
      bacteria. By LC-ESI(+)-MS, the photoproducts of CTC were identified. The direct
      photodegradation of CTC was involved in hydroxylation and N-demethyl/dedismethyl
      processes. The main photoproducts included the iso-CTC analog containing hydroxyl
      groups (m/z 511.4 and 495.4), and the N-demethyl/dedismethyl products of the
      photoproduct m/z 495.4 (m/z 481.3 and 467.4). In addition, the photochemical
      dechlorination of CTC led to tetracycline (m/z 445.5).

PMID- 22655386
TI  - Acid blue 25 adsorption on base treated Shorea dasyphylla sawdust: kinetic,
      isotherm, thermodynamic and spectroscopic analysis.
AB  - The potential of base treated Shorea dasyphylla (BTSD) sawdust for Acid Blue 25
      (AB 25) adsorption was investigated in a batch adsorption process. Various
      physiochemical parameters such as pH, stirring rate, dosage, concentration,
      contact time and temperature were studied. The adsorbent was characterized with
      Fourier transform infrared spectrophotometer, scanning electron microscope and
      Brunauer, Emmett and Teller analysis. The optimum conditions for AB 25 adsorption
      were pH 2, stirring rate 500 r/min, adsorbent dosage 0.10 g and contact time 60
      min. The pseudo second-order model showed the best conformity to the kinetic
      data. The equilibrium adsorption of AB 25 was described by Freundlich and
      Langmuir, with the latter found to agree well with the isotherm model. The
      maximum monolayer adsorption capacity of BTSD was 24.39 mg/g at 300 K, estimated
      from the Langmuir model. Thermodynamic parameters such as Gibbs free energy,
      enthalpy and entropy were determined. It was found that AB 25 adsorption was
      spontaneous and exothermic.

PMID- 22655387
TI  - Photodegradation of amoxicillin by catalyzed Fe3+/H2O2 process.
AB  - Three oxidation processes of UV-Fe3+(EDTA)/H2O2 (UV: ultraviolet light; EDTA:
      ethylenediaminetetraacetic acid), UV-Fe3+/H2O2 and Fe3+/H2O2 were simultaneously
      investigated for the degradation of amoxicillin at pH 7.0. The results indicated
      that, 100% amoxicillin degradation and 81.9% chemical oxygen demand (COD(Cr))
      removal could be achieved in the UV-Fe3+ (EDTA)/H2O2 process. The treatment
      efficiency of amoxicillin and COD(Cr) removal were found to decrease to 59.0% and
      43.0% in the UV-Fe3+/H2O2 process; 39.6% and 31.3% in the Fe3+/H2O2 process.
      Moreover, the results of biodegradability (biological oxygen demand
      (BOD5)/COD(Cr) ratio) revealed that the UV-Fe3+ (EDTA)/H2O2 process was a
      promising strategy to degrade amoxicillin as the biodegradability of the effluent
      was improved to 0.45, compared with the cases of UV-Fe3+/H2O2 (0.25) and
      Fe3+/H2O2 (0.10) processes. Therefore, it could be deduced that EDTA and UV light
      performed synergetic catalytic effect on the Fe3+/H2O2 process, enhancing the
      treatment efficiency. The degradation mechanisms were also investigated via UV
      Vis spectra, and high performance liquid chromatography-mass spectra. The
      degradation pathway of amoxicillin was further proposed.

PMID- 22655388
TI  - pH modeling for maximum dissolved organic matter removal by enhanced coagulation.
AB  - Correlations between raw water characteristics and pH after enhanced coagulation
      to maximize dissolved organic matter (DOM) removal using four typical coagulants
      (FeCl3, Al2(SO4)3, polyaluminum chloride (PACl) and high performance polyaluminum
      chloride (HPAC)) without pH control were investigated. These correlations were
      analyzed on the basis of the raw water quality and the chemical and physical
      fractionations of DOM of thirteen Chinese source waters over three seasons. It
      was found that the final pH after enhanced coagulation for each of the four
      coagulants was influenced by the content of removable DOM (i.e. hydrophobic and
      higher apparent molecular weight (AMW) DOM), the alkalinity and the initial pH of
      raw water. A set of feed-forward semi-empirical models relating the final pH
      after enhanced coagulation for each of the four coagulants with the raw water
      characteristics were developed and optimized based on correlation analysis. The
      established models were preliminarily validated for prediction purposes, and it
      was found that the deviation between the predicted data and actual data was low.
      This result demonstrated the potential for the application of these models in
      practical operation of drinking water treatment plants.

PMID- 22655389
TI  - Quantification of microcystin-producing and non-microcystin producing Microcystis
      populations during the 2009 and 2010 blooms in Lake Taihu using quantitative real
      time PCR.
AB  - Lake Taihu, a large, shallow hypertrophic freshwater lake in eastern China, has
      experienced lake-wide toxic cyanobacterial blooms annually during summer season
      in the past decades. Spatial changes in the abundance of hepatotoxin microcystin
      producing and nonmicrocystin producing Microcystis populations were investigated
      in the lake in August of 2009 and 2010. To monitor the densities of the total
      Microcystis population and the potential microcystin-producing subpopulation, we
      used a quantitative real-time PCR assay targeting the phycocyanin intergenic
      spacer (PC-IGS) and the microcystin synthetase gene (mcyD), respectively. On the
      basis of quantification by real-time PCR analysis, the abundance of potential
      toxic Microcystis genotypes and the ratio of the mcyD subpopulation to the total
      Microcystis varied significantly, from 4.08 x 10(4) to 5.22 x 10(7) copies/mL,
      from 5.7% to 65.8%, respectively. Correlation analysis showed a strong positive
      relationship between chlorophyll-a, toxic Microcystis and total Microcystis; the
      abundance of toxic Microcystis correlated positively with total phosphorus and
      ortho-phosphate concentrations, but negatively with TN:TP ratio and nitrate
      concentrations. Meanwhile the proportion of potential toxic genotypes within
      Microcystis population showed positive correlation with total phosphorus and
      ortho-phosphate concentrations. Our data suggest that increased phosphorus
      loading may be a significant factor promoting the occurrence of toxic Microcystis
      bloom in Lake Taihu.

PMID- 22655390
TI  - Decolorization of orange II using an anaerobic sequencing batch reactor with and
      without co-substrates.
AB  - We investigated the decolorization of Orange II with and without the addition of
      co-substrates and nutrients under an anaerobic sequencing batch reactor (ASBR).
      The increase in COD concentrations from 900 to 1750 to 3730 mg/L in the system
      treating 100 mg/L of Orange II-containing wastewater enhanced color removal from
      27% to 81% to 89%, respectively. In the absence of co-substrates and nutrients,
      more than 95% of decolorization was achieved by the acclimatized anaerobic
      microbes in the bioreactor treating 600 mg/L of Orange II. The decrease in mixed
      liquor suspended solids concentration by endogenous lysis of biomass preserved a
      high reducing environment in the ASBR, which was important for the reduction of
      the Orange II azo bond that caused decolorization. The maximum decolorization
      rate in the ASBR was approximately 0.17 g/hr in the absence of co-substrates and
      nutrients.

PMID- 22655391
TI  - Optimum conditions for the formation of Al13 polymer and active chlorine in
      electrolysis process with Ti/RuO2-TiO2 anodes.
AB  - A polyaluminum containing a high concentration of Al13 polymer and active
      chlorine (PACC) was successfully synthesized by a new electrochemical reactor
      using Ti/RuO2-TiO2 anodes. PACC can potentially be used as a dual-function
      chemical reagent for water treatment. The obtained results indicated that the
      formation of Al13 polymer and active chlorine, were the most active components in
      PACC responsible for coagulation and disinfection respectively. These components
      were significantly influenced by electrolyte temperature, current density, and
      stirring rate. It was observed that high electrolyte temperature favored the
      formation of Al13. Increasing current density and stirring rate resulted in high
      current efficiency of chlorine evolution, thus favoring the generation of Al13
      and active chlorine in PACC. When the PACC (Al(T) = 0.5 mol/L, basicity = 2.3)
      was prepared at the optimum conditions by electrolysis process, the Al13 polymer
      and active chlorine in product reached above 70% of Al(T) and 4000 mg/L,
      respectively. In the pilot scale experiment with raw polyaluminum chloride used
      as an electrolyte, PACC was successfully prepared and produced a high content of
      Al13 and active chlorine products. The pilot scale experiment demonstrated a
      potential industrial approach of PACC preparation.

PMID- 22655392
TI  - Nitrogen removal and simultaneous nitrification and denitrification in a
      fluidized bed step-feed process.
AB  - For urban wastewater treatment, we conducted a novel four-stage step-feed
      wastewater treatment system combined with a fluidized bed laboratory experiment
      to investigate chemical oxygen demand (COD), NH(4+)-N, and total nitrogen (TN)
      removal performance. The removal rates of COD, NH(4+)-N and TN were 88.2%, 95.7%,
      and 86.4% with effluent concentrations of COD, NH(4+)-N and TN less than 50, 8,
      and 10 mg/L, respectively. Biomass and bacterial activities were also measured,
      with results showing more nitrobacteria in the activated sludge than in the
      biofilm; however, bacterial activity of the biofilm biomass and the activated
      sludge were similar. Nitrogen concentrations during the process were also
      detected, with simultaneous nitrification and denitrification found to be
      obvious.

PMID- 22655393
TI  - Risk assessment of Giardia in rivers of southern China based on continuous
      monitoring.
AB  - The occurrence and risks of Giardia in China have been unclear to date, which has
      made it difficult to properly manage source water as well as to create reasonable
      drinking water standards. The levels of Giardia in river networks of several
      cities in Zhejiang Province, China were found to be in the range of 0-5
      oocysts/10 L in the rainy season in 2008. The mortality due to Giardia infection
      for people in this region was calculated to be from 0 to 1.95 x 10(-8) persons
      using a conditional probability equation. Based on multiple unboiled water intake
      routes, the disability-adjusted life years (DALYs) due to Giardia infection for
      people who consumed conventionally treated water was 0.625 (95% CI: 0.137-2.05)
      per 10(5) persons, with the symptom of hospitalization making the highest
      contribution to total DALYs (0.56 per 10(5) persons; 95% CI: 0.122-1.84). The
      DALYs decreased to 0.425 (95% CI: 0.137-2.05) per 10(5) persons per year for
      those consuming water treated with advanced technology. These values were lower
      than the acceptable risk (1.97 x 10(-5) DALYs per year). This study revealed the
      risk of Giardia infection to the people in river networks of Zhejiang Province
      for the first time, and provides a method to evaluate the risk of Giardia
      infection. The results are useful for the modification of drinking water quality
      standards based on cost-benefit analysis.

PMID- 22655394
TI  - Oxidative removal of acetaminophen using zero valent aluminum-acid system:
      efficacy, influencing factors, and reaction mechanism.
AB  - Commercial available zero valent aluminum under air-equilibrated acidic
      conditions (ZVA1/H+/air system) demonstrated an excellent capacity to remove
      aqueous organic compounds. Acetaminophen (ACTM), the active ingredient of the
      over-the-counter drug Tylenol, is widely present in the aquatic environment and
      therefore the treatment of ACTM-contaminated water calls for further research.
      Herein we investigated the oxidative removal of ACTM by ZVA1/H+/air system and
      the reaction mechanism. In acidic solutions (pH < 3.5), ZVA1 displayed an
      excellent capacity to remove ACTM. More than 99% of ACTM was eliminated within 16
      hr in pH 1.5 reaction solutions initially containing 2.0 g/L aluminum and 2.0
      mg/L ACTM at 25 +/- 1 degree C. Higher temperature and lower pH facilitated ACTM
      removal. The addition of different iron species Fe0, Fe2+ and Fe3+ into
      ZVA1/H+/air system dramatically accelerated the reaction likely due to the
      enhancing transformation of H2O2 to HO. via Fenton's reaction. Furthermore, the
      primary intermediate hydroquinone and the anions formate, acetate and nitrate,
      were identified and a possible reaction scheme was proposed. This work suggested
      that ZVA1/H+/air system may be potentially employed to treat ACTM-contaminated
      water.

PMID- 22655395
TI  - Assessment of source water contamination by estrogenic disrupting compounds in
      China.
AB  - Detection of estrogenic disrupting compounds (EDCs) in drinking waters around
      China has led to rising concerns about health risks associated with these
      compounds. There is, however, a paucity of studies on the occurrence and
      identification of the main compounds responsible for this pollution in the source
      waters. To fill this void, we screened estrogenic activities of 23 source water
      samples from six main river systems in China, using a recombinant two-hybrid
      yeast assay. All sample extracts induced significant estrogenic activity, with E2
      equivalents (EEQ) of raw water ranging from 0.08 to 2.40 ng/L. Additionally, 16
      samples were selected for chemical analysis by gas chromatography-mass
      spectrometry. The EDCs of most concern, including estrone (E1), 17beta-estradiol
      (E2), 17alpha-ethinylestradiol (EE2), estriol (E3), diethylstilbestrol (DES),
      estradiol valerate (EV), 4-t-octylphenol (4-t-OP), 4-nonylphenols (4-NP) and
      bisphenol A (BPA), were determined at concentrations of up to 2.98, 1.07, 2.67,
      4.37, 2.52, 1.96, 89.52, 280.19 and 710.65 ng/L, respectively. Causality
      analysis, involving comparison of EEQ values from yeast assay and chemical
      analysis identified E2, EE2 and 4-NP as the main responsible compounds,
      accounting for the whole estrogenic activities (39.74% to 96.68%). The proposed
      approach using both chemical analysis and yeast assay could be used for the
      identification and evaluation of EDCs in source waters of China.

PMID- 22655396
TI  - Probabilistic ecological risk assessment for three chlorophenols in surface
      waters of China.
AB  - Individual and combined assessment of risks of adverse effects to aquatic
      ecosystems of three chlorophenols (CPs), including 2,4-dichlorophenol (2,4-DCP),
      2,4,6-trichlorophenol (2,4,6-TCP) and pentachlorophenol (PCP), were conducted. A
      probabilistic approach based on the concentrations of CPs in surface waters of
      China was used to determine the likelihood of adverse effects. The potential risk
      of CPs in surface waters of China was determined to be of concern, especially PCP
      and mixtures of CPs. The risks of adverse effects were examined as the joint
      probabilities of exposure and response. The joint probability for PCP was 0.271
      in the worst case and 0.111 in the median case, respectively. Based on the
      cumulative probability, 5% of aquatic organisms included in the assessment would
      be affected 21.36% of the time in the worst case and 5.99% of the time in median
      case, respectively. For the mixtures of CPs, the joint probability were 0.171 in
      the worst case and 0.503 in median case, respectively and 5% of species would be
      affected 49.83% of the time for the worst case and 12.72% in the median case,
      respectively. Risks of effects of the individual CPs, 2,4-DCP and 2,4,6-TCP were
      deemed to be acceptable with a overlapping probability of < 0.1 with 5% of
      species being affected less than 4% of the time.

PMID- 22655397
TI  - Concentration and source identification of polycyclic aromatic hydrocarbons and
      phthalic acid esters in the surface water of the Yangtze River Delta, China.
AB  - The pollution from polycyclic aromatic hydrocarbons (PAHs) and phthalic acid
      esters (PAEs) in the surface water of the rapidly urbanized Yangtze River Delta
      region was investigated. Fourteen surface water samples were collected in June
      2010. Water samples were liquid-liquid extracted using methylene chloride and
      analyzed by gas chromatography-mass spectrometry. Concentrations of PAHs and PAEs
      ranged 12.9-638.1 ng/L and 61-28550 ng/L, respectively. Fluoranthene,
      naphthalene, pyrene, phenanthrene, di-2-ethylhexyl phthalate, and di-n-butyl
      phthalate were the most abundant compounds in the samples. The water samples were
      moderately polluted with benzo[a]pyrene according to China's environmental
      quality standard for surface water. The two highest concentrations of PAHs and
      PAEs occurred in samples from Taihu Lake, Wuxi City and the western section of
      Yangchenghu Lake. Potential sources of pollution at S7 were petroleum combustion
      and the plastics industry, and at Yangchenghu Lake were petroleum combustion and
      domestic waste. Pollution in samples from the Beijing-Hangzhou Grand Canal
      originated from diesel engines. There were no obvious sources of pollution for
      the other water samples. These results can be used as reference levels for future
      monitoring programs of pollution from PAHs and PAEs.

PMID- 22655398
TI  - Biological sulfate removal from acrylic fiber manufacturing wastewater using a
      two-stage UASB reactor.
AB  - A two-stage UASB reactor was employed to remove sulfate from acrylic fiber
      manufacturing wastewater. Mesophilic operation (35 +/- 0.5 degree C) was
      performed with hydraulic retention time (HRT) varied between 28 and 40 hr. Mixed
      liquor suspended solids (MLSS) in the reactor was maintained about 8000 mg/L. The
      results indicated that sulfate removal was enhanced with increasing the ratio of
      COD/SO4(2-). At low COD/SO4(2-), the growth of the sulfate-reducing bacteria
      (SRB) was carbon-limited. The optimal sulfate removal efficiencies were 75% when
      the HRT was no less than 38 hr. Sulfidogenesis mainly happened in the sulfate
      reducing stage, while methanogenesis in the methane-producing stage. Microbes in
      sulfate-reducing stage performed granulation better than that in methane
      producing stage. Higher extracellular polymeric substances (EPS) content in
      sulfate-reducing stage helped to adhere and connect the flocculent sludge
      particles together. SRB accounted for about 31% both in sulfate-reducing stage
      and methane-producing stage at COD/SO4(2-) ratio of 0.5, while it dropped
      dramatically from 34% in sulfate-reducing stage to 10% in methane-producing stage
      corresponding to the COD/SO4(2-) ratio of 4.7. SRB and MPA were predominant in
      sulfate-reducing stage and methane-producing stage respectively.

PMID- 22655399
TI  - Innovators achieve more than reforms ever will.

PMID- 22655400
TI  - New regulatory head plans to tackle inappropriate FtP referrals.

PMID- 22655401
TI  - Major study confirms link between nurse staff levels and care quality.

PMID- 22655402
TI  - Public sector pays staff more than necessary, argues the Treasury.

PMID- 22655403
TI  - Internship applications triple as graduates struggle to find work.

PMID- 22655404
TI  - 'I want to make a difference by improving outcomes for patients'.

PMID- 22655405
TI  - Breaking barriers.
AB  - Johanne Tomlinson detected connections between high anxiety levels,
      confrontational behaviour and self-harm in offenders in her care at a men's
      prison. Her observations led to the launch of an anxiety management service,
      which she now runs alongside her regular nursing work. Her commitment has
      resulted in her being named Nursing Standard's nurse of the year 2012.

PMID- 22655406
TI  - Inspired to keep going.

PMID- 22655407
TI  - Behind the headlines.

PMID- 22655408
TI  - Not just an IT project.
AB  - Innovative use of information technology is improving patient outcomes and making
      nurses' working lives easier. Nurses at a Birmingham trust are using handheld
      computers to record vital observations and give early warning to senior
      clinicians if a patient is deteriorating. The system reflects a trend for
      healthcare technology based around the needs of clinicians and patients.

PMID- 22655409
TI  - The burden of bureaucracy.
AB  - Paperwork is commonly cited as one of the worst features of nurses' jobs. While
      some documentation is essential, much form-filling could be done more efficiently
      or delegated to non-nursing staff. Some organisations are revolutionising how
      nurses handle bureaucratic tasks, releasing them to improve their practice and
      spend more time at the bedside.

PMID- 22655410
TI  - Strategies to prevent gonorrhoea reinfection in men.
AB  - Gonorrhoea is a common sexually transmitted infection that is on the increase in
      the male population in the UK. Gonorrhoea is becoming increasingly resistant to
      antibiotics, making it harder to treat patients effectively. Sexual health nurses
      therefore have a vital role to play in preventing gonorrhoea reinfection. This
      article examines the ways in which sexual health nurses can work with male
      patients to prevent reinfection and effectively maintain their sexual health.

PMID- 22655411
TI  - An investigation into the activities of the clinical nurse specialist.
AB  - AIM: To assess the activities of clinical nurse specialists (CNSs), examining
      work patterns, job plans and team structures, especially the balance of patient
      facing and non-patient-facing activity. METHOD: A quantitative evaluation was
      conducted using diary cards at Imperial College Healthcare NHS Trust. CNSs were
      asked to record their activity for each ten-minute period of the working day over
      two weeks. RESULTS: Data were received from 236 of 261(90.4%) possible
      respondents and more than one million minutes of data were submitted. On average,
      CNSs spent 41% of their time in direct patient-facing activities and an
      additional 21.5% in patient-related activities. However, there was wide variation
      in how time was spent between individuals and teams, and across divisions within
      the trust. CNSs estimated that 16.4% of their clinical activity may have
      prevented an adverse event or patient attendance at hospital. CONCLUSION: Data
      generated from this evaluation will be used to develop coherent job plans for
      individuals and teams of CNSs and to identify which nurse-led activities are
      being reimbursed by commissioners of services.

PMID- 22655412
TI  - Pre-operative assessment of elective surgical patients.
AB  - Patients due to undergo elective surgery who are not considered to be medically
      fit, may have their operation postponed or even cancelled. Not only will this
      result in significant anxiety for the person, but it will also have financial
      implications for the hospital, in terms of lost theatre time. In an attempt to
      prevent postponing or cancelling scheduled surgery, pre-operative assessment is
      essential to ensure that the patient is physically and emotionally prepared. This
      article examines the main components of pre-operative assessment and how
      addressing any problems before surgery can help to improve post-operative
      outcomes for patients.

PMID- 22655413
TI  - MRSA.

PMID- 22655414
TI  - Robust professional back-up.

PMID- 22655415
TI  - Taking action on poor practice.

PMID- 22655416
TI  - On the lookout for men.

PMID- 22655417
TI  - Spectacles.

PMID- 22655418
TI  - The five Cs.

PMID- 22655419
TI  - Bacteria's fluoride fighter revealed.

PMID- 22655420
TI  - Improving the oral health of California's most vulnerable populations.

PMID- 22655421
TI  - A comprehensive school-based/linked dental program: an essential piece of the
      California access to care puzzle.
AB  - California children suffer more from dental disease than any other chronic
      childhood disease. Disparities in access and oral health are disproportionately
      represented among children from minority and low-income families. A comprehensive
      school-based/linked dental program is one essential ingredient in addressing
      these problems. Described here are the goals, program elements, and challenges of
      building a seamless dental services system that could reduce barriers care,
      maximize resources, and employ best practices to improve oral health.

PMID- 22655422
TI  - The impact of additional dental providers in the dental labor market on the
      income of private practice dentists.
AB  - This study estimates the impact that the entrance of hypothetical allied dental
      professionals into the dental labor market may have on the earnings of currently
      practicing private practice dentists. A simulation model that uses the most
      reliable available data was constructed and finds that the introduction of
      hypothetical allied dental professionals into the competitive California dental
      labor market is likely to have relatively small effects on the earnings of the
      average dentist in California.

PMID- 22655423
TI  - Access to dental care and the capacity of the California dental care system.
AB  - The authors estimated the following levels of technical efficiency for three
      types of dental practices in California where technical efficiency is defined as
      the maximum output that can be produced from a given set of inputs: generalists
      (including pediatric dentists), 96.5 percent; specialists, 77.1 percent;
      community dental clinics, 83.6 percent. Combining this with information on
      access, it is estimated that the California dental care system in 2009-10 could
      serve approximately 74 percent of the population.

PMID- 22655425
TI  - Chasing 40 winks.

PMID- 22655424
TI  - The capacity of the dental systems in California study: a review.

PMID- 22655426
TI  - Is this the world we want?

PMID- 22655427
TI  - Comments on "Teaching the art of medicine".

PMID- 22655428
TI  - Optimum utilization of cholecystokinin cholescintigraphy (CCK-HIDA) in clinical
      practice: an evidence based review.
AB  - Laparoscopic cholecystectomy remains one of the most commonly performed
      operations in the United States. Of the cholecystectomies performed,
      approximately 30% are carried out for a diagnosis of gallbladder dyskinesia, for
      which diagnosis is based on a reduced gallbladder ejection fraction as determined
      by a sincalide (cholecystokinin) stimulated hepatobiliary iminodiacetic scan (CCK
      HIDA). Despite the widespread acceptance of this practice standardization of the
      test methodology and high quality data indicating efficacy of cholecystectomy in
      the treatment of this condition are lacking. This manuscript reviews this problem
      in detail based on the current available literature.

PMID- 22655429
TI  - Intact bronchogenic cyst presenting as a lung mass provoking a pleural effusion:
      a rare presentation.
AB  - This case report describes a 49 year old woman with an intra-parenchymal
      bronchogenic cyst masked on chest x-ray examination by a pleural effusion. The
      cyst was intact. It is likely that the cyst provoked the pleural effusion by
      repetitive mechanical irritation of the pleura. At surgery, the cyst was removed
      and the pleural effusion drained without recurrence. The cyst was unilocular and
      measured 8.5 x 7.0 x 0.8 cm with a smooth and glistening lining. It was filled
      with approximately 300 ml of clear fluid. Microscopic examination confirmed the
      bronchogenic cyst. This is the first case of an intact intra-parenchymal
      bronchogenic cyst associated with a pleural effusion that was not due to rupture
      of the cyst, infection or malignancy.

PMID- 22655430
TI  - Moyamoya in a non-Asian patient: a case report and review of the literature.
AB  - Moyamoya disease (MMD) has historically been diagnosed in the Japanese
      population. However, newer studies have demonstrated worldwide distribution. Of
      note, patients of Appalachian descent with no known Asian ancestry have presented
      with MMD. We are presenting a case of MMD in an Appalachian, non-Asian patient
      who presented to the neurosurgical service with a severe headache of four days
      duration. The patient was found to have multiple hemorrhagic infarcts on CT and
      was admitted to the ICU. Cerebral angiography findings confirmed the diagnosis of
      MMD. Our case provides information regarding signs and symptoms, diagnostic
      neuroimaging findings, and treatment modalities for MMD.

PMID- 22655431
TI  - "Hepatitis C (HCV) treatment is not a "one size fits all".
AB  - During the past ten years, there has been a remarkable increase in the number and
      spectrum of medications used for the treatment of viral hepatitis infections
      including the hepatitis C virus infection (HCV). Still there is considerable
      variability among physicians in the use and duration of treatment of the
      currently available medications. Therefore, the current literature on the HCV
      therapy will be reviewed and summarized.

PMID- 22655432
TI  - Acromegaly caused by growth hormone releasing hormone (GHRH) secreting tumor in
      multiple endocrine neoplasia (MEN-1).
AB  - We are presenting the clinical features, diagnostic work up and treatment of
      acromegaly caused by Growth hormone releasing hormone (GHRH) secreting
      neuroendocrine tumor (NECT) in a case of multiple endocrine neoplasia type 1 (MEN
      1). A 36 year old man, known case of MEN-1 presented with acromegalic features.
      He has high IGF-1, GH and very high GHRH levels with a pancreatic head tumor and
      pituitary mass. He had high GHRH arteriovenous gradient across pancreatic tumor
      and underwent tumor resection, Post operative GHRH level fell dramatically. Tumor
      had high GHRH m-RNA level. Acromegalic patients with MEN-1 should be screened for
      ectopic GHRH secretion. Measurement of GHRH arteriovenous gradient across NECT or
      mRNA for GHRH in resected tumor can confirm the ectopic source. Treatment of
      choice is surgical resection of the tumor. Somatostatin analogue is an
      alternative because of its dual action in the pituitary gland and the NECT. Life
      long surveillance is needed as recurrence chance is high.

PMID- 22655433
TI  - Physician-patient communication: breaking bad news.
AB  - Physicians often struggle with how to manage the task of breaking bad news with
      patients. Moreover, the arduous nature of the task can contribute to physician
      detachment from the patient or an avoidance of breaking the news in a timely
      manner. A plan of action can only improve physician confidence in breaking bad
      news, and also make the task more manageable. Over a decade ago, Rabow and McPhee
      offered a strategy; the ABCDE plan, which provided a patient centered framework
      from which to deliver troubling news to patients and families. At the heart of
      this plan was the creation of a safe environment, the demonstration of timely
      communication skills, and the display of empathy on the physician's part. Careful
      consideration of the doctor's own reactions to death and dying also played an
      important role. A close review of the five tenets of this plan indicates the
      relevance of Rabow and McPhee's strategy today. The patient base in our nation
      and state continues to be older, on average, and physicians are faced with
      numerous patients who have terminal illness. A constructive plan with specific
      ideas for breaking bad news can help physicians effectively navigate this
      difficult task.

PMID- 22655434
TI  - Schwannoma of the ulnar nerve: a case report and review of the literature.
AB  - We report a case of a large ulnar nerve schwannoma, a rare type of soft tissue
      neoplasm. Diagnostic pearls are described to facilitate a more accurate and
      timely diagnosis. These characteristics include mobility, Tinel's sign, MRI
      target sign, S100 histological staining, Antoni patterns, and others. With a
      correct diagnosis, the tumor can be extirpated with preservation of nerve
      function and a low risk of recurrence.

PMID- 22655435
TI  - Influenza vaccination among West Virginia pregnant and postpartum women 2009
      2010.

PMID- 22655436
TI  - Wiring up our home. Pioneers of the patient-centered medical home concept see a
      mix of strategic, process and IT success factors involved.
AB  - Thepatient-centered medical home concept is moving forward nationwide, with
      countless variations on a general theme, along with some universals. Healthcare
      and healthcare IT leaders agree: wiring up this home means putting all the
      strategic, process, and technology pieces together for success.

PMID- 22655437
TI  - Unifying a patient-centered medical home. The Adirondack pilot makes strides in
      coordinating patient care despite interoperability challenges.
AB  - To overcome an aging provider population, the Adirondack Region Medical Home
      Pilot in upstate New York gathered payers and providers to enhance care
      coordination and manage chronic diseases, all the while dealing with challenges
      of interoperability and physician documentation.

PMID- 22655438
TI  - Risk and reward in the cloud. Choosing a cloud vendor involves weighing risks
      versus benefits.
AB  - More hospitals are looking to the cloud as a viable way to store clinical,
      imaging, and financial data. Experts acknowledge its advantages, but caution it's
      a step that requires careful planning and vetting of potential cloud vendors.

PMID- 22655439
TI  - Targeting chronic illness together. Health plans support providers through
      predictive analytics.
AB  - Health insurers that used to focus on individual claims are now looking across
      their entire membership to better define the appropriate level of financial risk
      to assign and to drive the right kinds of interventions. Many are making a
      determined effort to share their predictive analytics findings with clinicians.

PMID- 22655440
TI  - An avalanche of deadlines and timelines in healthcare. A healthcare expert lends
      her much-needed perspective to the broad sweep of mandates confronting all
      provider organizations and physicians.

PMID- 22655442
TI  - Tennessee HIE to begin data exchange. Middle Tennessee eHealth Connect readies
      its core hospital contributors and seeks payer participation.

PMID- 22655441
TI  - Looking at care quality progress. Premier's Richard Bankowitz, M.D., offers his
      perspectives on the achievements being logged by Quest participant hospitals.

PMID- 22655443
TI  - Overcoming interoperability challenges through HIE. Huntington Hospital creates
      its own community information exchange to coordinate care, aid practice
      viability.

PMID- 22655444
TI  - Readmissions and the mechanics of care transitions. How leaders at Michigan's
      Spectrum Health System are finding ways to address the readmissions of CHF
      patients.

PMID- 22655445
TI  - Cloud -based communication. Versatile communication platform helps foster
      collaborative care.

PMID- 22655446
TI  - Device connectivity. Virtua links disparate biomedical devices to its enterprise
      wide EMRs.

PMID- 22655447
TI  - Policy plays catch up to mobile technology. ONC, OCR discussion highlights gulf
      between real-world usage and security guidelines.

PMID- 22655448
TI  - Nurturing your employees. Tips for retaining top employees at a time when demand
      for HCIT talent has never been higher.

PMID- 22655449
TI  - The XI Asian Congress on Nutrition (July, 2011) in Singapore, and capacity
      building in Indonesia: a personal commentary.

PMID- 22655450
TI  - Correlates of physical activity level among hemodialysis patients in Selangor,
      Malaysia.
AB  - INTRODUCTION: There is mounting evidence demonstrating the importance of adequate
      physical activity to promote better well-being among hemodialysis patients.
      Available data pertaining to the levels of physical activity and its determinants
      among hemodialysis patients is, however, scarce in Malaysia. The objectives of
      this study are hence to determine the levels of physical activity and it
      associated factors among hemodialysis patients. METHODOLOGY: A total of 70
      subjects were recruited from three dialysis centres in Selangor. A face-to-face
      interview was conducted to obtain socio-demographic data and subjects' knowledge
      on dietary sources. Medical history, biochemical parameters and weight status
      were obtained from medical records. Physical activity level (PAL) was assessed
      using the Global Physical Activity Questionnaire (GPAQ). RESULTS: A total of
      81.4% and 18.6% of the respondents had low and moderate PALs, respectively. Thus,
      none of the respondents had high PAL. Serum creatinine, education level, personal
      income and knowledge score on potassium-related medical complications were
      factors found to correlate significantly with PAL. Multiple linear regression
      analysis showed that higher PAL was predicted by a lower knowledge score on
      dietary sodium source, higher education and higher serum creatinine. CONCLUSION:
      Despite consistent documentation of the potential positive impact of physical
      exercise on hemodialysis outcomes, the level of physical activity remains low
      among these patients. It is hoped that these findings can add to the existing
      body of knowledge and serve as a supporting document for the formulation of
      appropriate interventions to improve the status of physical activity among
      hemodialysis patients in Malaysia.

PMID- 22655451
TI  - Dietary compliance and its association with glycemic control among poorly
      controlled type 2 diabetic outpatients in Hospital Universiti Sains Malaysia.
AB  - INTRODUCTION: Compliance with medical nutrition therapy is important to improve
      patient outcomes. The purpose of this study was to determine dietary compliance
      and its association with glycemic control among outpatients with poorly
      controlled type 2 diabetes mellitus (T2DM) in Hospital Universiti Sains Malaysia
      (HUSM). METHODS: In this cross-sectional study, patients who had a glycosylated
      hemoglobin (HbA1c) level of at least 6.5%, after attending a diet counseling
      session at the Outpatient Dietetic Clinic, HUSM, were enrolled. Out of 150
      diabetic patients reviewed between 2006 and 2008, 61 adults (32 men and 29 women)
      agreed to participate in this study. A questionnaire-based interview was used to
      collect socio-demographic, clinical and diabetes self-care data. The patient's
      dietary compliance rate was determined by the Summary of Diabetes Self-Care
      Activities (SDSCA) measure. Anthropometric and biological measurements were also
      taken. RESULTS: Only 16.4% of the respondents adhered to the dietary regimen
      provided by dietitians. Among the 7 dietary self-care behaviours, item number 6
      (eat lots of food high in dietary fibre such as vegetable or oats) had the
      highest compliant rate (54.1%); whereas item number 3 (eat five or more servings
      of fruits and vegetables per day) had the lowest compliant rate (23.0%). There
      was a significant association between gender (p = 0.037) and fasting blood sugar
      (FBS) (p = 0.007) with the compliance status. CONCLUSION: Dietary non-compliance
      is still common among T2DM patients. Dietitians need to improve their skills and
      use more effective intervention approaches in providing dietary counseling to
      patients.

PMID- 22655452
TI  - Prevalence and causes of low birth weight in India.
AB  - INTRODUCTION: The aims of the study are (i) to understand inter-zone and
      interstate variation of low birth weight (LBW) and (ii) to determine the key
      variables to reduce LBW in India. METHODS: Using the latest National Family
      Health Survey (NFHS) data of 2005-06 which showed the percentage distribution of
      LBW infants, ANOVA and post-hoc test were performed to determine the spatial
      variation of birth weight. The covariates which influence LBW fell into three
      categories: (i) social variables which included location, mother's education,
      religion, access of mothers to newspapers, television and family structure; (ii)
      economic variable namely, the wealth index, and (iii) biological variables which
      consisted of sex of the children, birth order, and mother's body mass index
      (BMI). Three models of Logistic regression were carried out to examine the
      influence of the combinations of these direct and indirect factors. RESULTS: In
      India, nearly 20% of new borns have LBW. Males have less frequency of LBW than
      females. The North-east zone has the lowest prevalence of LBW while the north
      zone has the highest. Mother's education, access to TV and nuclear family, and
      intake of iron tablets are the most important socio-economic influences on the
      determination of birth weight in India. CONCLUSION: It is essential to provide
      proper diet and nutritional care of mothers during pregnancy. Increased education
      of mothers through programmes in TV and newspapers articles have significant
      roles to play in reducing LBW in India.

PMID- 22655453
TI  - Socio-demographic and psychosocial factors associated with physical activity of
      working woman in Petaling Jaya, Malaysia.
AB  - INTRODUCTION: This study was conducted on 215 working women from four private
      corporate companies in a suburb in Malaysia to determine the factors related to
      their physical activity levels. METHODS: Data were collected using a
      questionnaire which included socio-demographic characteristics, the International
      Physical Activity Questionnaire (IPAQ), perceived barriers and benefits to
      physical activity, self-efficacy to physical activity and an 8-item questionnaire
      on current behavioral stage of physical activity. RESULTS: The majority of the
      respondents were Malay (81.9%) with 10.2% being Chinese and 7.9% Indian. Most of
      the respondents were executives (64.2%), while the rest were non-executives
      (24.7%) and managers (11.2%). The mean weight, height, BMI and waist
      circumference were 59.4 +/- 13.1 kg, 1.6 +/- 0.6 m, 23.7 +/- 4.8 kg/m2 and 77.0
      +/- 12.1cm respectively. In this sample, 24.7% and 7.9% were overweight and obese
      respectively, while 34% were at risk of abdominal obesity. A total of 28.8% of
      the respondents had low physical activity level, while 48.8% and 22.3% were in
      the moderate and high physical activity categories respectively. An association
      was found between monthly income (chi2 = 110.17; p < 0.05) and current behavioral
      stage of physical activity (chi2 = 27.527; p < 0.05) with physical activity, but
      no relationship was found between job category and physical activity category
      (chi2 = 8.940; p > 0.05). Physical activity category was also positively
      correlated with perceived barriers (r = 0.227, p < 0.05) and benefits to physical
      activity (r = 0.280, p < 0.05). However, physical activity was not associated
      with self-efficacy to physical activity. CONCLUSION: In this sample of working
      women, socio-demographic and psychosocial factors (except self-efficacy to
      physical activity) were found to have an association with physical activity level
      of the respondents. Further studies should be conducted to confirm these findings
      in the general working women population.

PMID- 22655454
TI  - Physical activity, eating behaviour and body image perception among young
      adolescents in Kuantan, Pahang, Malaysia.
AB  - INTRODUCTION: A cross-sectional study was conducted to determine physical
      activity, eating behaviour, body weight management knowledge, perception of body
      image and their association with body weight status of adolescents. METHODS:
      Respondents were 360 adolescents, aged between 13 to 14 years, from six randomly
      selected secondary schools in Kuantan, Pahang. Physical activity, eating
      behaviour, body weight management knowledge and perception of body image were
      measured by the Physical Activity Questionnaire for Older Children (PAQ-C),
      Eating Attitude Test-26 (EAT-26), Weight Management Knowledge Inventory (WMKI)
      and Contour Drawing Rating Scale (CDRS), respectively. RESULTS: Almost half of
      the respondents were categorised as having a normal BMI, while 30.3% were
      severely thin and thin and 20.3% were overweight and obese. Mean physical
      activity score was 2.06 +/- 0.45 with more males (35.0%) being physically active
      than females (17.3%). Mean eating behaviour score was 15.41 +/- 10.37, with 27.8%
      of the respondents being at-risk for eating disorders. Mean weight management
      knowledge score was 5.35 +/- 1.80, with more females (77.7%) having higher mean
      scores than males (42.3%). Further, mean discrepancy score for body image
      perception was 1.24 +/- 0.99, with 78.1% of the respondents being dissatisfied
      with their current body size. Positive associations were found between eating
      behaviour (r = 0.28, p < 0.05) and body image (r = 0.35, p < 0.05) with BMI.
      Respondents with high eating behaviour scores and body image discrepancy scores
      were more likely to have greater BMI. CONCLUSION: This study shows the need for
      healthy eating and body image intervention programmes to prevent overweight and
      obesity problems among adolescents.

PMID- 22655455
TI  - Dietary trans fatty acids intake and its relation to dyslipidemia in a sample of
      adults in Depok city, West Java, Indonesia.
AB  - INTRODUCTION: The Basic Health Research of the Ministry of Health Indonesia in
      2008 reported that the single most important cause of death was stroke, in both
      urban and rural populations. The risk factors underlying the cause of death are
      associated with hypertension, obesity and dyslipidemia. The purpose of this study
      was to determine the mean intake of trans fatty acids and its relation to
      dyslipidemia in a sample of Indonesian adults. METHODS: A cross-sectional study
      was conducted on a total of 180 adult male and female respondents aged 35-60
      years living in rural and urban areas of Depok city, West Java. Dietary intake
      was assessed by means of 24-hour recall and semi-quantitative FFQ. RESULTS: The
      mean intake of trans fatty acids was 0.48% of total calories (urban 0.40% and
      rural 0.55%). The prevalence of dyslipidemia in the rural and urban subjects were
      61.1% and 66.7%, respectively. There was a statistically significant relationship
      between trans fatty acids intake and hypercholesterolemia and
      hypertriglyceridemia. CONCLUSION: The intake of trans fatty acid among the
      Indonesian adults studied was half the recommended level. The high prevalence of
      dyslipidemia found indicates the need for intervention to reduce the rising
      incidence of cardiovascular diseases in Indonesia.

PMID- 22655456
TI  - Impact of nutrition education on knowledge and haemoglobin status of hill women
      in Uttarakhand State of India.
AB  - INTRODUCTION: This study aimed to examine the impact of the use of single vs.
      combination of media on nutritional knowledge and haemoglobin status of women in
      a rural hill area in Uttarakhand State, India. METHODS: Women from three villages
      were selected randomly and divided into three groups namely, print media group (n
      = 59), multimedia group (n = 53) and control group (n = 111). The print media
      group was exposed to nutrition education through the use of calendars on anaemia
      for 60 days; the multimedia group was given nutrition education through a
      combination of media including calendars, video films, and group discussions for
      60 days. RESULTS: At pre-exposure stage, 62.7% of the women in the print media
      group, 67.9% of the multimedia group, and 66.7% of the control group had a low
      nutrition knowledge level. After exposure, the print media group and the
      multimedia group showed a significant rise in nutrition knowledge, with the
      multimedia group scoring significantly higher than the print media group.
      Overall, 69.1% of the women were anaemic with mean haemoglobin concentration of
      10.74 +/- 0.86 g/dl. A non-significant rise in mean haemoglobin concentrations in
      the experimental groups was found at post-exposure stage. CONCLUSION: Calendars
      and video films are effective in increasing nutrition knowledge of illiterate
      hill women. Use of mass media programmes of longer duration should be encouraged
      to combat the nutritional problems of rural communities.

PMID- 22655457
TI  - Impact of okra (Abelmoschus esculentus) seed flour on nutrients, functional
      properties and zinc bioavailability of plantain flour.
AB  - INTRODUCTION: In Nigeria, nursing mothers are advised to give their infants
      plantain flour paste 'amala ogede' with 'ewedu' Corchorus olitorius soup during
      the process of weaning. Over-matured okra is typically discarded resulting in
      substantial post-harvest waste; the seed could be processed into okra seed flour
      for the fortification of plantain flour. The aim of this study is to evaluate the
      effect of the addition of okra seed flour on the nutrients, functional
      properties, minerals and zinc bioavailability of plantain flour. METHODS: Okra
      seed flour was used to fortify plantain flour in the ratio 90:10, 80:20 and
      70:30. RESULTS: The addition of okra seed flour to the plantain flour resulted in
      a significant increase in the protein, fat, fibre and ash content of the
      fortified plantain flour, while that of moisture and carbohydrate decreased. The
      mineral levels of Zn, K and Fe increased significantly while the calcium content
      decreased. The calculated phytate--zinc molar ratio and [Ca][Phytate]/[Zn] molar
      ratio of the fortified plantain flour were below the critical levels. CONCLUSION:
      The study showed that fortifying plantain flour with okra seed flour resulted in
      an increase in several nutrients, rendering the zinc more bioavailable. This
      fortified food has potential as a complimentary food in Nigeria.

PMID- 22655458
TI  - Antioxidant and cytotoxicity effect of rice bran phytic acid as an anticancer
      agent on ovarian, breast and liver cancer cell lines.
AB  - INTRODUCTION: Phytic acid (PA) has been shown to have positive nutritional
      benefits. There are also claims that it is able to prevent cancer through its
      antioxidant capability. This study investigated antioxidant activity and
      cytotoxic effect of PA extracted from rice bran against selected cancer cell
      lines (i.e. ovarian, breast and liver cancer). METHODS: Cytotoxicity activity of
      PA was investigated using MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)]-2H-tetrazolium, inner salt] assay while
      the antioxidant activity of PA extract, commercial PA and butylated
      hydroxytoluene (BHT) was determined by using five different assays: ferric
      thiocyanate (FTC) and thiobarbituric acid (TBA) assay, beta-carotene bleaching
      method, DPPH radical scavenging assay and ferric reducing antioxidant power
      (FRAP) assay. RESULTS: PA extracted from rice bran induced marked growth
      inhibition in ovary, breast and liver cancer cells with 50% growth inhibition
      concentration (IC50) values of 3.45, 3.78 and 1.66 mM, respectively but exhibited
      no sensitivity towards a normal cell line (3T3). The PA extract was also found to
      exert antioxidant activity when tested using the FTC, TBA, FRAP and beta-carotene
      bleaching methods but antioxidant activity could not be attributed to scavenging
      free radical species as measured by DPPH radical scavenging assay. CONCLUSION:
      The PA extract from rice bran displayed safe and promising anticancer properties
      in selected cancer cell lines and it is believed that its antioxidant capability
      is the likely contributor to the observed anticancer properties.

PMID- 22655459
TI  - Antioxidant capacity and total phenol content of commonly consumed selected
      vegetables of Bangladesh.
AB  - INTRODUCTION: The purpose of the study was to determine the antioxidant capacity
      (AC) and total phenolic content (TPC) of selected commonly consumed Bangladeshi
      vegetables and herbs. METHODS: Hydrophilic extracts from edible portions of ten
      vegetables and two herbs were analysed. The total phenolic amount ranged from
      27.65 +/- 1.45 mg to 1.08 +/- 0.15 Gallic Acid Equivalent (GAE)/ g on a fresh
      weight (FW) basis. Contents of total phenol were determined
      spectrophotometrically according to the Folin-Ciocalteau method and the
      antioxidant capacity was determined by 2,2-diphenyl-1-1-picrylhydrazyl radical
      scavenging activity (DPPH-RSA). RESULTS: Antioxidant capacity varied from 8328.80
      +/- 29.15 to 0.61 +/- 0.19 micromol Trolox Equivalent (TE)/g of FW. Ipomoea
      leaves showed the highest AC (8328.80 +/- 29.15 micromol TE/g), while the lowest
      AC (0.61 +/- 0.19 micromol TE/g) was seen in radish. A linear relationship was
      observed between Trolox Equivalent Antioxidant Capacity (TEAC) values and total
      phenol. Antioxidant capacity of the assayed samples correlated significantly and
      positively with total phenolic content (R2 = 0.814, p < 0.01). Vegetables with
      high polyphenol like Ipomoea leaves and mint showed high AC with the exception of
      raw banana which demonstrated moderate AC though it contained high TPC. Moderate
      TPC vegetables like amaranths and coriander leaves did not show substantial AC.
      CONCLUSION: The data indicates that indigenous vegetables containing high
      polyphenols may be a potential source of dietary antioxidants.

PMID- 22655460
TI  - Influence of socio-demographic factors on physical activity participation in a
      sample of adults in Penang, Malaysia.
AB  - INTRODUCTION: Given the importance of physical activity to health, this study
      investigated the socio-demographic determinants of physical activity
      participation in a sample of adults in Penang. METHODS: Through convenience
      sampling, a total of 398 adults agreed to answer a prepared questionnaire on
      their socio-demographic background and physical activity participation. The data
      were analysed using the binary logit model. Frequent physical activity
      participation is defined as taking part more than 11 times in leisure-time
      physical activity such as swimming and jogging, each time lasting more than 15
      minutes in a typical month, whereas participation that is less than the frequency
      and time duration specified above is referred to as infrequent physical activity.
      RESULTS: Age, male, being Chinese, high educational attainment, self-rated
      excellent health status and presence of family illnesses are positively
      associated with the likelihood of frequent participation in physical activity. On
      the contrary, being married, having low income and residing in rural areas are
      inversely related with the propensity of frequent physical activity
      participation. CONCLUSION: The majority in this sample of adults do not
      participate in physical activity frequently, and the reasons given include lack
      of health awareness, limited leisure time, budget constraints, and lack of sports
      amenities.

PMID- 22655461
TI  - Glycemic index determination of vegetable and fruits in healthy Bangladeshi
      subjects.
AB  - INTRODUCTION: Fruits and vegetables are an important part of the diet especially
      for their complex carbohydrates, dietary fibre and micronutrients. The present
      study investigated the glycemic index (GI) of a vegetable [carrot (Daucas
      carota)] and fruits [banana (Chapa kola) Musa Sp. and plum (Bau kul) Zizyphus
      mauritiana] of Bangladeshi origin. METHODS: Fourteen healthy Bangladeshi
      subjects, comprising 7 males and, 7 females, with mean age of 26 +/- 3 years, BMI
      22 +/- 3 kg/m2, waist-hip ratio of 0.89 +/- 0.01 and 0.84 +/- 0.04 respectively
      for males and females. Under a cross-over design, they consumed equi-carbohydrate
      amounts (25 g of total available carbohydrate) of the test foods and two times
      glucose as reference food (25 g of total carbohydrate), with a run in period of 7
      days between the consecutive items. Serum glucose levels were determined at 0,
      30, 60, 90, and 120 min. The GIs was calculated. RESULTS: The carrot, banana and
      plum samples showed significantly lower serum glucose values (incremental area
      under the curve 30.4 +/- 12.6, 37.3 +/- 19.2 and 41.8 +/- 20.7 respectively) than
      glucose (132.7 +/- 36.0). The carrot showed a lower GI value than banana and plum
      respectively (23 +/- 9, 30 +/- 18 and 32 +/- 15). CONCLUSION: The vegetable and
      fruit samples tested of Bangladesh origin were shown to have comparatively low GI
      values.

PMID- 22655462
TI  - Editor's choice March 2012: the different challenges in leprosy around the world.

PMID- 22655463
TI  - An overview of training and development needs.

PMID- 22655464
TI  - Leprosy figures: no time for self-complacency.

PMID- 22655465
TI  - A research strategy to develop new tools to prevent leprosy, improve patient care
      and reduce the consequences of leprosy. Five year leprosy research strategy
      approved by ILEP Board October 2011.

PMID- 22655466
TI  - Motives and determinants for residence change after leprosy diagnosis, central
      Brazil.
AB  - OBJECTIVE: To determine the extent of population movement after diagnosis with
      leprosy and to describe the underlying motives and determinants for relocation.
      DESIGN: A cross-sectional study was conducted among those newly diagnosed with
      leprosy in 79 endemic municipalities in the state of Tocantins, central Brazil.
      Individuals were identified through the National Information System for
      Notifiable Diseases (SINAN) database and interviewed with structured
      questionnaires. RESULTS: In total, 224 (20.9%) out of 1070 individuals relocated
      after their diagnosis with leprosy. Respondents moved to another neighbourhood in
      the same municipality (n = 178, 79.5%), followed by another municipality in
      Tocantins state (n = 26, 11.6%) and in another state (n = 11, 4.9%). The primary
      motives and/or determinants for relocation were: home ownership (n = 55, 28.4%),
      familial reasons (n = 43, 19.2%), to seek better living conditions (n = 27,
      13.9%), employment (n = 26, 11.6%), and better neighbourhood (n = 22, 9.8%).
      Other motives were related to better access to leprosy diagnosis/treatment (n =
      11, 4.9%), owner-terminated rental (n = 5, 2.2%), personal finances/could not
      afford housing (n = 4, 1.8%). Perceived stigma due to leprosy was mentioned by
      one participant (0.5%). CONCLUSION: In Tocantins state, population movement is
      lower among individuals recently diagnosed with leprosy, as compared to the
      overall population. The primary motives for relocation after leprosy diagnosis
      were related to lifestyle changes. Stigma and treatment-related reasons did not
      appear to be common motives for population movement. These results may reflect
      policy changes instituted from the Brazilian Program of Leprosy Control to
      decentralise leprosy services and intensify health education campaigns within a
      broader concept of Information, Education and Communication.

PMID- 22655467
TI  - The production of social discourse on Hansen' disease and health education
      materials in Brazil: a skin patch as something harmless or a serious disease?
AB  - AIMS: Hansen's disease is endemic in Brazil and government control programmes
      promote publicity campaigns to increase the detection of new cases through the
      production and distribution of educative material. OBJECTIVES: This study
      analyses a set of 276 educational materials produced by governmental and non
      governmental organisations that work to control Hansen's disease in Brazil. It
      describes the content of the materials and the way the issues were approached.
      DESIGN: It is a qualitative study that adopts the theoretical and methodological
      framework of the semiology of social discourse. RESULTS: Analysis reveals that
      the relations between the enunciator and recipient of the materials are
      asymmetrical as a result of the technical and educational language employed.
      Biomedical information forms the basis for social representations an practices of
      Hansen's disease, as opposed to historical collective knowledge of 'leprosy'. The
      prioritised topics are: signs and symptoms of the disease, treatment stigma, cure
      and surveillance. CONCLUSIONS: The institutionalisation of public education on
      Hansen's disease in Brazil was not limited simply to the change of terminology
      from 'leprosy' to 'Hansen's disease,' but was shaped also by new educational
      practices. It is recommended that the evaluation and production of new materials
      be incorporated into the set of activities already carried out in health centres
      so as to expand the discussion on content, language and the best way to address
      the disease in the materials.

PMID- 22655468
TI  - Lack of effects of the TNF-alpha and IL-10 gene polymorphisms in Mexican patients
      with lepromatous leprosy.
AB  - Several human genetic variants have been associated with susceptibility or
      resistance to leprosy. The aim of this study was to assess whether gene
      polymorphisms of -308 G/A TNF-alpha and -819 T/C IL-10 are associated with
      lepromatous leprosy in Mexican mestizos patients from northwest Mexico. We
      genotyped these polymorphisms by means of polymerase chain reaction (PCR) and
      restriction fragment length polymorphisms (RFLPs) in 68 patients with lepromatous
      leprosy and 144 healthy Mexican Mestizos controls. We found that the -308G TNF
      alpha allele was predominant in both cases (94.3%) and controls (92.3%) without
      statistical significance and the frequencies of -819C IL-10 allele were also
      similar for the cases (56.0%) and controls (59.0%). These negative findings
      suggest that other genes or polymorphisms may be important in the susceptibility
      to leprosy infection in the Mexican mestizos.

PMID- 22655469
TI  - The pattern of bacterial isolates and drug sensitivities of infected ulcers in
      patients with leprosy in ALERT, Kuyera and Gambo hospitals, Ethiopia.
AB  - INTRODUCTION: Leprosy remains a public health problem, mainly in Africa, Asia and
      Latin America. Leprosy has many complications that include leprosy reactions,
      development of plantar and hand ulcerations, lagophthalomus and corneal
      anesthesia. OBJECTIVES: In Ethiopia there is scarce information on the pattern of
      bacterial isolates and drug sensitivities of infected ulcers in patients with
      leprosy. This study was undertaken to identify the bacteriology of infected
      ulcers and to determine their antimicrobial susceptibility pattern. STUDY DESIGN:
      A descriptive cross-sectional study was conducted in 245 informed and consented
      leprosy patients with infected ulcers visiting ALERT, Kuyera and Gambo hospitals
      during the period August 2006 to May 2007. MATERIAL AND METHODS: Wound aspirate
      specimens were collected from ulcers of each patient aseptically and inoculated
      into standard bacteriological media. Antimicrobial susceptibility testing was
      performed for all isolates according to the criteria of the National Committee
      for Clinical Laboratory Standards (NCCLS) by disk diffusion method. RESULTS: Of
      the 245 patients investigated, 64.1% were males and 35.9% females (P < 0.05). The
      average age of the patients was 50 years (age range 13 to 92 years). According to
      Ridley-Jopling classifications, patients presented with TT (3.7%), BT, (31.4%),
      BL (44.5%) and LL (15.9%) types of leprosy. Plantar and hand ulcers were observed
      in 92.2% and 7.8% of patients, respectively. According the patients, the
      commonest cause of their ulcers was 'spontaneous' (56.7%). There were 44% Gram
      positive and 56% Gram negative bacteria (P > 0.05). Proteus spp. accounted for
      29.5% of the total isolates followed by Staphylococcus spp. (28.8%), beta
      hemolytic streptococci (15.1%) and different types of Gram-negative bacteria
      (26.2%). Multiple organisms (two or three) were isolated from 19.6% patients. Of
      the 212 wound samples cultured anaerobically, 5.2% were positive for anaerobic
      culture. In this study both Gram-positive and Gram negative bacteria showed
      decreased sensitivity to most antimicrobial agents tested. CONCLUSION: Proteus
      spp. was the most common isolate from infected ulcers. Ciprofloxacin, norfloxacin
      and gentamicin were the most effective drugs against the tested bacteria mainly
      for Gram-negative bacteria. This refers to the in vitro-sensitivity during the
      study period. The results of this study may help inform clinicians about the
      selection of an antibiotic in situations where use of an antibiotic may be
      indicated.

PMID- 22655470
TI  - Evaluation of leprosy surveillance system in the Amazon region, Brazil, 2001
      2007.
AB  - OBJECTIVES: We evaluated the leprosy surveillance system in the Amazon region,
      Brazil, 2001-2007, using evaluation guidelines from the US Centers for Disease
      Control and Prevention. RESULTS: We found that the leprosy surveillance system in
      the Amazon region is simple, presents good data quality and is representative in
      describing the sociodemographic profile and clinical classification of cases. The
      predictive value positive is high and its sensitivity is unknown. The grade two
      disability artificially increased in 2007 during the transition to a new version
      of the information system. The cases are reported, receive treatment and are
      discharged from the system as treatment completion in a timely fashion.
      Nevertheless, the dermatological and neurological examination introduces
      complexity to the system, which may account for the irregular data quality
      related to the evaluation of the disability degree, the system's lack of
      representativeness to describe mild neurological manifestations and low
      proportion of household contacts investigated. CONCLUSIONS: Despite its
      limitations, the leprosy surveillance system proved to be useful. Recommendations
      for its improvement were issued based on the results found. More data on
      surveillance systems in endemic countries are needed to facilitate valid
      comparisons between country indicators.

PMID- 22655471
TI  - One year follow up of a cohort of suspected leprosy cases: findings from a
      leprosy 'Selective Special Drive' in Gadchiroli district, Maharashtra, India.
AB  - OBJECTIVES: The study involves a follow-up visit in 2010, to hyper-endemic
      Gadchiroli district of Maharashtra, India, to evaluate the current status of
      those suspected in 2009 of having skin/nerve lesions suggestive of leprosy, and
      to study the interactions between such people and the State leprosy programme.
      DESIGN: The study cohort comprised of those confirmed with leprosy (n = 151 and
      157/233 absentee 'suspects' who were not examined by the study team in 2009 in 14
      of 45 Primary Health Centres (PHCs). At follow-up, the treatment status of the
      confirmed cases was checked from PHC registers and cross-checked by direct
      questioning of patients and their views were sought on PHC leprosy services. The
      157 absentee 'suspects' were queried about the reasons for their absence.
      RESULTS: Thirty nine 'absentee suspects' were found to have leprosy. A notable
      feature of the follow-up visit was that 114 people in the communities, other than
      those listed as 'suspects' by Community Health Workers (CHWs), voluntarily sought
      out the team for their opinion on hypopigmented/anaesthetic lesions, which
      resulted in a further 39 new cases being brought to light. (Total new cases =
      78). The follow-up revealed discrepancies (100% vs. 75%) between PHC records and
      testimonies of the registered patients about regularity of treatment;
      irregularity of MDT supply was cited by some for dropping out of treatment. Other
      reasons proffered for irregularity were lepra reaction, fear of stigma, ignorance
      about leprosy and preference for faith healers. Medical Officers of PHCs were not
      trained in the management of lepra reactions; that task, along with disability
      care being entrusted to a paramedical worker of an NGO during periodic visits.
      CONCLUSIONS: There are remediable lacunae in the recording and dispensing of MDT
      by the State apparatus, as well as a need for refresher training in leprosy
      diagnosis for PHC staff, and in lepra reaction management for medical officers.
      The large number (78) of new cases detected in the follow-up, in part of
      Gadchiroli district strongly suggests more to-be-discovered cases in the
      communities.

PMID- 22655472
TI  - Analysis of newly detected leprosy in Sohag Governorate, Upper Egypt, 2004-2008.
AB  - INTRODUCTION: Leprosy is a chronic and complex infectious illness; the new-case
      detection rate is better than prevalence as an indicator of disease trends. This
      study presents an analysis of pattern of new cases of leprosy detected annually
      from 2004 to 2008 in Sohag Governorate, Upper Egypt. PATIENTS AND METHODS: Data
      about patients with newly diagnosed leprosy were collected from Sohag leprosy
      hospital, the main referral centre in the governorate. Case detection rates (CDR)
      were calculated for each year by dividing the newly diagnosed cases by mid-year
      populations for the same year. RESULTS: 587 patients were newly diagnosed between
      2004 and 2008. The mean age of patients at diagnosis was 34 years, 62% were
      males, and 11% were children below 15 years of age. The overall leprosy case
      detection rate was 3-1/100,000 population and it decreased from 3.4/100,000
      population in 2004 to 2.8/100,000 population in 2008. Ninety three percent were
      classified as multibacillary, and 20.4% had Grade 2 disability at diagnosis.
      CONCLUSIONS: Leprosy remains a health problem in Sohag Governorate. It is
      possible that new cases are being detected late owing to inadequate community
      awareness of the disease. Leprosy control activities should be provided in
      primary health care units in order to detect new cases, and continued
      surveillance is required to detect relapses and to ensure good patient compliance
      with treatment.

PMID- 22655473
TI  - Effectiveness of social skills training for reduction of self-perceived stigma in
      leprosy patients in rural India--a preliminary study.
AB  - OBJECTIVES: To assess the effectiveness of social skills training in leprosy
      patients to raise self-esteem and reduce self-perceived stigma. DESIGN: Five
      leprosy patients were given 10 day-long group-sessions of social skills training
      over 3 weeks. Training involved: identification of the emotions and concerns of
      patients when interacting socially; analysis of positive and negative social
      interactions and non-verbal and verbal skills training. Role-plays, videos and
      live models were used. Self-esteem and a reduction in self-perceived stigma were
      assessed qualitatively before and after training using semi-structured
      interviews. Assessment of change was scored under the indicators: self
      perception, family, wider community and job. Patients were assessed for
      displaying new ways of interacting with people and changes in expectations for
      the future. RESULTS: Qualitative analysis of the interviews before and after
      training suggested that social skills training could raise the self-esteem of
      leprosy patients and combat self-perceived stigma. Increase in self-esteem, as
      evident through the verbal interactions with the interviewers and behavioural
      changes in the community, were noted in the majority of patients. CONCLUSION:
      Social skills training along with counseling may be able to increase the self
      esteem of leprosy patients, and so be a useful part of leprosy rehabilitation
      schemes to try and combat the stigma of leprosy.

PMID- 22655474
TI  - Leprotic neuropathy misdiagnosed as chronic inflammatory demyelinating
      polyneuropathy.

PMID- 22655475
TI  - Florid reactive periostitis ossificans of long bones and digits associated with
      reaction in a patient with leprosy.
AB  - Florid reactive periostitis ossificans is a rare bone lesion usually occurring in
      the small, tubular bones of the hands and feet. This entity is a benign and
      aggressive periosteal reaction associated with soft tissue swelling that appears
      similar to a bone lesion that radiographically and clinically mimics an
      infectious or neoplastic process. Typically the lesions occurs in an adolescent
      or young adult and presents as a small area of painful swelling and erythema over
      the affected bone. The cause of florid reactive periostitis ossificans is not
      exactly known though many authors have postulated varied etiopathogenesis for the
      same condition. In this report, is a very rare and unusual example of this entity
      that has been observed in association with erythema nodosum leprosum (ENL) a type
      2 lepra reaction in a Leprosy patient.

PMID- 22655476
TI  - Anaplastic large cell lymphoma and lepromatous leprosy: a rare coexistence.
AB  - Lepromatous leprosy (LL) has been reported in the literature with Non Hodgkin
      Lymphoma and rarely with Hodgkin Lymphoma. However, an extensive search of the
      literature shows no case report describing anaplastic large cell lymphoma (ALCL)
      in association with LL. We report a case of a young male with LL who was found to
      have ALCL. This is an interesting case of coexistence of an endemic infectious
      disease and a rare lymphoma involving the same lymph node, with a brief review of
      the literature.

PMID- 22655477
TI  - Trigeminal trophic syndrome complicating a case of borderline tuberculoid
      leprosy.
AB  - An example of trigeminal trophic syndrome presenting as ulceration of ala nasi in
      a case of borderline tuberculoid leprosy is reported. To the best of our
      knowledge, this is only the second case report of this manifestation in leprosy
      to be documented.

PMID- 22655478
TI  - Epidemiological and clinical features of pyogenic spondylodiscitis.
AB  - Pyogenic spondylodiscitis (PS) is an uncommon but important infection, that
      represents 3-5% of all cases of osteomyelitis. The annual incidence in Europe has
      been estimated to be from 0.4 to 2.4/100,000. A has been reported, with peaks at
      age less than 20 years and in the group aged 50-70 years. The incidence of PS
      seems to be increasing in the last years as a result of the higher life
      expectancy of older patients with chronic debilitating diseases, the rise in the
      prevalence of immunosuppressed patients, intravenous drug abuse, and the increase
      in spinal instrumentation and surgery. PS is in most cases a hematogenous
      infection. Staphylococcus aureus is the most frequent causative microorganism,
      accounting for about one half of the cases of PS. Gram-negative rods are
      causative agents in 7-33% of PS cases. Coagulase-negative staphylococci (CoNS)
      have been reported in 5-16% of cases. Staphylococcus epidermidis is often related
      to post-operative infections and intracardiac device-related bacteremia.
      Unremitting back pain, characteristically worsening during the night, is the most
      common presenting symptom, followed by fever that is present in about one half of
      the cases. The mortality of PS ranges from 0 to 11%. In a significant number of
      cases, recrudescence, residual neurological defects or persistent pain may occur.

PMID- 22655479
TI  - Imaging of spondylodiscitis.
AB  - BACKGROUND: Spinal infections (pyogenic or non-pyogenic) are increasing in
      incidence and are a common cause of morbidity in high-risk patients (elderly,
      immunocompromised patients, diabetic patients, drug addicts, and patients with
      sickle-cell disease). AIM: To provide an overview of the radiological features of
      spinal infections, focusing on magnetic resonance (MR) imaging, and to illustrate
      the differential diagnosis. MATERIALS AND METHODS: We reviewed the spine imaging
      of 118 patients with spinal infections from our files. All patients underwent
      radiography and MR imaging examinations. computed tomography (CT) was performed
      in 96 patients. RESULTS: MR imaging has greatly contributed to prompt diagnosis,
      thus allowing implementation of timely appropriate treatment. CONCLUSIONS: Prompt
      diagnosis and treatment are essential to prevent serious bone and joint
      destruction, and severe neurologic sequelae.

PMID- 22655480
TI  - The role of nuclear medicine in the diagnosis of spondylodiscitis.
AB  - BACKGROUND: The diagnosis of spondylodiscitis can be difficult, because the
      patients history, subjective symptoms and physical findings are often
      inconclusive, particularly in the early stages. AIM: To perform an overview on
      the role of nuclear medicine procedures with single photon emission tomography
      (SPET) and positron emission tomography (PET) tracers in the diagnosis of
      spondylodiscitis. MATERIALS AND METHODS: A literature review about bone
      scintigraphy, Gallium-67-citrate scintigraphy, labeled leukocytes scintigraphy
      and PET was performed. Main findings of the literature were reported. RESULTS:
      Bone scintigraphy is a sensitive and widely available nuclear medicine technique,
      but it is characterized by low specificity. Gallium-67-citrate scintigraphy is
      often used as a complement to bone scintigraphy to enhance the specificity of the
      study and to detect extra-osseous sites of infection. Labeled leukocytes
      scintigraphy is not a useful method in the diagnosis of spondylodiscitis.
      Fluorine-18-fluorodeoxyglucose positron emission tomography is a sensitive method
      and could potentially be useful in the diagnosis of spondylodiscitis and in the
      evaluation of treatment response. Nevertheless, scientific literature about this
      topic is still limited. CONCLUSIONS: Overall, nuclear medicine procedures play a
      useful role in the diagnosis of spondylodiscitis identifying functional
      abnormalities which precede morphological changes. Therefore, nuclear medicine
      procedures may complement or integrate morphological imaging findings in patients
      with suspected spondylodiscitis.

PMID- 22655481
TI  - Biopsy for suspected spondylodiscitis.
AB  - BACKGROUND: Vertebral biopsy is fundamental in determining whether a spinal
      lesion is of infectious or neoplastic etiology. Accurate diagnosis is critical
      for proper medical and/or surgical treatment and consequently for the prognosis
      of the patient. CT-guided percutaneous spinal biopsy (CTSB) may minimize the risk
      of contamination and complications. AIM: To demonstrate the importance and
      efficacy of CTSB and subsequent microbiologic/histological examination in the
      diagnosis of spinal lesions, particularly for those of an infectious nature.
      MATERIALS AND METHODS: Two series of spinal infection patients. Prospective
      series of 69 patients (2009-2011), 24 of whom underwent CTSB. Retrospective
      series of 130 patients (1999-2008), 65 of whom underwent CTSB. All patients had
      microbiologic and histological testing of biopsy samples, when possible. RESULTS:
      For the 2009-2011 patient series, histological examination yielded a diagnosis in
      81.8% of cases, microbiologic culture and PCR for Mycobacterium tuberculosis in
      45.8%. For the 1999-2008 series, histological examination yielded a diagnosis in
      69% of cases, culture in 38.5%. Spinal lesions in 4 patients with previous
      histories of malignancy were assumed to be metastatic and treated with radiation
      at outside institutions. After biopsy, all were revealed to be spondylodiscitis.
      CONCLUSIONS: Percutaneous CT-guided needle biopsy is the mainstay of diagnosis
      for spine lesions of unknown etiology, thus guiding appropriate treatment.
      Histological diagnosis, when possible, is critical before initiation of therapy
      and may be helpful in cases where cultures are negative. In the case of a spinal
      lesion of unknown origin, even in the setting of a previous malignancy,
      metastasis should not be assumed; infection and new primary lesions should always
      be considered as part of the differential diagnosis.

PMID- 22655482
TI  - Medical and surgical treatment of pyogenic spondylodiscitis.
AB  - BACKGROUND: Pyogenic vertebral osteomyelitis (PVO) represents approximately 2-7%
      of all cases of osteomyelitis. The approach to the treatment of PVO may be
      conservative, which includes antibiotic therapy and orthopaedic treatment, or
      surgical. AIM: To overview conservative and surigical approaches to PVO. METHODS:
      A literature review was performed using the Pubmed database to identify studies
      published in the last 20 years, addressing the treatment of PVO. RESULTS:
      Empirical antibiotic treatment of PVO, while waiting for the results of cultures
      or in culture-negative cases, should include broad spectrum agents in association
      with agents active on Staphylococcus (S.) aureus. Based on local epidemiological
      data, antibiotics active on methicillin resistant S. aureus (MRSA) should be
      included. Once an organism has been identified, antibiotics should be initially
      administered intravenously but the optimal duration of antimicrobial therapy is
      unclear. Studies have reported that the incidence of treatment failure was higher
      when i.v. therapy was administered for less than 4 weeks. Rifampin is widely used
      in the combination therapy of PVO, but no controlled trials are available to
      define weather this approach is beneficial. Many PVO need a surgical treatment
      and can represent a real challenge for the orthopaedic surgeon. Anterior and
      posterior cervical, thoracic, lumbar approaches and the relatives surgical
      strategies are reported in this review. Moreover, recently the mininvasive
      posterior stabilization have been proposed as a efficient alternative to open
      surgery in elderly with severe comorbidities. Possible advantages and limitations
      of this technique are also reported. CONCLUSIONS: Further research is needed in
      order to define the optimal duration of antibiotic therapy, and the benefits and
      limitations of open or mini-invasive surgical techniques.

PMID- 22655483
TI  - Post-operative spondylodiscitis.
AB  - Postoperative spine infections (PSIs) are a frequent and dreaded complication of
      spine surgery. Although different studies have been published, the prevalence of
      PSIs is thought to be about 5% for most spine surgical procedures. Different risk
      factors have been identified for PSIs. Among the others, extensive soft tissue
      dissection, longer operative time, soft tissue devitalization, and use of
      surgical instrumentation have been associated with higher risks of infection.
      Direct inoculation during surgery is the common infection route for PSIs. Gram
      positive cocci (such as Staphylococcus aureus, Staphylococcus epidermidis and
      beta-hemolytic streptococci) are the most common pathogens. Gram-negative
      bacteria also play a role in PSIs and may be associated with systemic illness and
      multisystem organ failure. A high level of suspicion is of paramount importance
      in early diagnosis of PSIs. Clinical symptoms of PSIs may be subtle and the
      infection may become apparent only in its late stages. Early diagnosis is the
      most important prognostic factor for PSIs. Although blood tests (i.e. ESR, CRP,
      and white blood cell count) and imaging studies (most commonly MRI) can be
      useful, it must be clear to the clinician that diagnostic modalities, either
      tissue biopsy or blood cultures, are of the utmost importance for diagnosing PSIs
      and devising a correct antibiotic therapy. Antibiotic therapy with early bracing
      (or bed rest) is the most commonly used treatment method for PSIs. Nevertheless,
      a more aggressive surgical treatment may be required in some patients. The goals
      of surgical treatment are to help the eradication of the infection, provide an
      adequate wound closure, and maintain spine column mechanical stability.

PMID- 22655484
TI  - Tuberculous spondylodiscitis: epidemiology, clinical features, treatment, and
      outcome.
AB  - BACKGROUND: Tuberculous spondylodiscitis (TS) is a rare but serious clinical
      condition which may lead to severe deformity and early or late neurological
      complications. AIM: To discuss certain aspects of the approach to TSs, focusing
      upon epidemiology, diagnosis, and treatment outcome. MATERIALS AND METHODS: For
      the purpose of this review, a literature search was performed using the Pubmed
      database through to 19th October 2011 to identify studies published in the last
      20 years, concerned in epidemiological, clinical, diagnostic, and therapeutical
      aspects of TS in adults. Only studies drafted in English language and reporting
      case series of more than 20 patients have been included. RESULTS: TS has been
      reported to accounts for 1-5% of all TB cases, and for about 50% of the cases of
      articulo-skeletal TB infections. Despite the actual availability of more
      effective diagnostic tools, early recognition of TS remains difficult and a high
      index of suspicion is needed due to the chronic nature of the disease and its
      insidious and variable clinical presentation. A prompt diagnosis is required to
      improve long term outcome, and a microbiological confirmation is recommended to
      enable appropriate choice of anti-mycobacterial agents. Surgery has an important
      role in alleviating pain, correcting deformities and neurological impairment, and
      restoring function. CONCLUSIONS: Further studies are required to assess the
      appropriate duration of anti-microbial treatment, also in regarding of a combined
      surgical approach.

PMID- 22655485
TI  - Microbiological and immunological diagnosis of tuberculous spondylodiscitis.
AB  - BACKGROUND: Tuberculous spondylodiscitis is one the many manifestations of active
      tuberculosis (TB) and can result following primary infection or, more frequently,
      from reactivation of active TB in subjects with latent TB. Definitive diagnosis
      of tuberculous spondylodiscitis requires the identification of Mycobacterium
      tuberculosis in the biological sample following microbiological analysis. AIM: To
      summarize the recent advancement in the diagnosis of TB, focusing on classical
      and molecular microbiological procedures, providing an overview on the recent
      advancements in the understanding of TB pathogenesis and their implications for
      the immunological diagnosis MATERIALS AND METHODS: Isolation in culture of the
      bacilli and detection using molecular tools are the gold standards, though
      sensitivity of these assays is significantly lower compared to what observed for
      pulmonary TB, making diagnosis of spinal TB challenging. RESULTS: The use of the
      interferon-gamma release assays (IGRAs) for the immunological diagnosis of TB
      infection could be of help and shall precede the invasive techniques, such as
      biopsy or surgery, required to obtain the biological sample. IGRAs measure the
      presence of effector T cells in the blood that can readily respond to an
      antigenic stimuli by secreting cytokines, and that are an indication of the
      presence of the bacilli in vivo. IGRAs are more sensitive and specific than the
      intradermic reaction of Mantoux, though both these immunological tests cannot
      distinguish between latent TB infection and active TB. CONCLUSIONS: A modern
      diagnosis of TB spondylodiscitis should rely on the use of microbiological and
      immunological assays and the latter could potentially be of great help in
      monitoring therapy effectiveness.

PMID- 22655486
TI  - Surgical treatment of tuberculous spondylodiscitis.
AB  - BACKGROUND: Most patients affected by spinal tuberculosis can be successfully
      treated conservatively with chemotherapy, external bracing and prolonged rest.
      Nevertheless, kyphotic deformity, spinal instability and neurological deficit
      remain a common complication associated with conservative approach. AIM: To
      illustrate different indications and treatment modalities for tuberculous
      spondylodiscitis, focusing on the role of surgery as an adjuvant of effective
      chemotherapy in the management of selected patients. MATERIALS AND METHODS:
      Various early and late surgical procedures are recommended to treat spinal
      tuberculosis. The Authors analyzed surgical indications, approaches,
      complications and outcomes comparing their experience with available Literature.
      RESULTS: Conservative management is preferable in patients without vertebral
      instability and deformity; in presence of abscesses, invasive radiological
      techniques in combination with abscess drainage and chemotherapy are recommended.
      In patients with vertebral collapse, kyphotic deformity or abscess formation,
      vertebral instability or neurological deficits, anterior radical debridement,
      anterior strut grafting and anterior instrumentation is an optimal standardized
      procedure. In patients with involvement of more than two vertebral levels or
      lumbosacral junction and in those whose sagittal alignment is markedly deformed
      with segmental kyphosis, and in patients who have difficulty in undergoing
      anterior instrumentation, posterior instrumentation is recommended in combination
      with anterior radical debridement and anterior strut grafting in one or two
      staged procedures. CONCLUSIONS: Since surgery for spinal tuberculosis is
      demanding, it should be performed only after taking into account the risks and
      benefits in operable patients. Various surgical procedures are recommended to
      treat spinal tuberculosis but the common goals are to eradicate the infection and
      to prevent or to treat neurologic deficits or spinal deformity.

PMID- 22655487
TI  - Three-dimensional, extended field-of-view ultrasound method for estimating large
      strain mechanical properties of the cervix during pregnancy.
AB  - Cervical shortening and cervical insufficiency contribute to a significant number
      of preterm births. However, the deformation mechanisms that control how the
      cervix changes its shape from long and closed to short and dilated are not clear.
      Investigation of the biomechanical problem is limited by (1) lack of thorough
      characterization of the three-dimensional anatomical changes associated with
      cervical deformation and (2) difficulty measuring cervical tissue properties in
      vivo. The objective of the present study was to explore the feasibility of using
      three-dimensional ultrasound and fundal pressure to obtain anatomically-accurate
      numerical models of large-strain cervical deformation during pregnancy and enable
      noninvasive assessment of cervical-tissue compliance. Healthy subjects (n = 6)
      and one subject with acute cervical insufficiency in the midtrimester were
      studied. Extended field-of-view ultrasound images were obtained of the entire
      uterus and cervix. These images aided construction of anatomically accurate
      numerical models. Cervical loading was achieved with fundal pressure, which was
      quantified with a vaginal pressure catheter. In one subject, the anatomical
      response to fundal pressure was matched by a model-based simulation of the
      deformation response, thereby deriving the corresponding cervical mechanical
      properties and showing the feasibility of noninvasive assessment of compliance.
      The results of this pilot study demonstrate the feasibility of a biomechanical
      modeling framework for estimating cervical mechanical properties in vivo. An
      improved understanding of cervical biomechanical function will clarify the
      pathophysiology of cervical shortening.

PMID- 22655488
TI  - Synergistic effects of ultrasound-activated microbubbles and doxorubicin on short
      term survival of mouse mammary tumor cells.
AB  - The primary focus of this paper is to quantify the therapeutic synergism when
      combining ultrasound, ultrasound contrast agents (UCAs) and doxorubicin for
      breast cancer treatment using an in vitro experimental configuration with mouse
      mammary tumor (4T1) cells. The 4T1 cells were grown in 96 well plates and allowed
      to grow to 90% confluency. A 1-MHz focused (f/3) single-element transducer was
      used to expose the microbubbles (MBs) (Definity) with ultrasound near the surface
      of the cells. After the ultrasound exposure, different doses of doxorubicin were
      added and incubated for 24 hours at 37 degrees C, 100% humidity and 5% CO2. The
      efficacies of the drug only and ultrasound-activated MBs combined with drug
      therapies to kill cells were then quantified by analyzing the cell viability
      after 24 hours of treatment using the MTT Cell Proliferation Assay. The combined
      therapy resulted in 60 +/- 5.9% of cell viability compared to 82 +/- 4.5% when
      only doxorubicin was used. The cell viability was 72 +/- 5.8% when only
      ultrasound-activated MBs were used with a similar acoustic pressure condition. No
      significant increase in cell death was observed for higher concentrations of
      doxorubicin whereas higher peak negative pressure of the ultrasound wave resulted
      in increased cell death.

PMID- 22655489
TI  - The effects on cordal and leaflet stiffness of severe apical, posterior, and
      outward papillary displacement in advanced ventricular mechanism heart failure
      and mitral insufficiency.
AB  - BACKGROUND AND AIM OF THE STUDY: During the normal opening and closing of the
      mitral valve there is a finely tuned interaction between the changing ventricular
      dimensions and fluid pressures, the movement of papillary muscles apically,
      posteriorly and apart during diastole and in the opposite direction during
      systole, interactions between leaflets and their controlling cords, and the fluid
      dynamic forces being exerted on them. The main rough zone cords and the smooth
      zone of the anterior leaflet are under maximum tension in systole, but retain
      some tension throughout the cycle. The free edge cords and the rough zone of the
      leaflets can have no or minimal tension during diastole, and much less tension
      than the main rough zone cords and the smooth zone in systole. The variability of
      the form and distribution of rough zone cords influences the flexibility of the
      rough zone. The net effect of this interaction is a valve that opens rapidly for
      unobstructed forward flow, and closes at the end of the cycle with minimal
      leakage. The apical displacement of, usually, the right inferior papillary muscle
      as a result of ischemic ventricular disease pulls the leaflets into separation
      because the origins of cords supporting the anterior and posterior leaflets arise
      specifically from the anterior and posterior sides of each papillary muscle.
      Myocardial ischemia producing apical papillary displacement can be associated
      with heart failure and mitral insufficiency. Annuloplasty reducing the annulus to
      less than the normal systolic dimension can be effective in eliminating both
      insufficiency and heart failure when the papillary displacement is dominantly
      apical. In more severe cases of heart failure and mitral insufficiency, the mid
      ventricular dimensions increase to a more severe degree, and both papillary
      muscles are displaced outwards and posteriorly. METHODS AND RESULTS: Static in
      vitro experiments performed on three human and nine pig hearts showed that the
      outward papillary displacements increased the tension on first-order cords,
      rendering the anterior leaflet and the central scallop of the posterior leaflet
      stiff. The addition of posterior displacement caused the anterior leaflet to
      become directed at an angle to the displaced papillary muscles, and the scallops
      of the posterior leaflet to be perpendicularly splayed around the posterior left
      ventricular wall, such that the valve no longer opened or closed correctly.
      CONCLUSION: The valve no longer opens or closes properly, and annuloplasty is no
      longer of use in restoring valve function.

PMID- 22655490
TI  - Interatrial block and P-terminal force: a reflection of mitral stenosis severity
      on electrocardiography.
AB  - BACKGROUND AND AIM OF THE STUDY: Interatrial block (IAB), a frequently overlooked
      conduction delay between the atria, is defined as prolonged P-wave on the
      electrocardiogram (ECG). Previously, IAB has been shown to be an indicator of
      dilated and impaired left atrial function, and a predictor of both atrial
      fibrillation and embolic stroke. The study aim was to test the hypothesis that,
      on ECG, IAB with P-terminal force can reflect the echocardiographic severity of
      mitral stenosis (MS). METHODS: Patients with rheumatic MS who were referred to a
      single cardiac center for echocardiography between July and October 2009, and who
      met the study entry criteria (echocardiographically documented rheumatic MS),
      were invited to participate. Consequently, 116 such patients were studied
      prospectively, while a group of age- and gender-matched subjects without
      echocardiographic signs of rheumatic valve involvement served as controls.
      Transthoracic echocardiography was performed in all subjects. RESULTS: A positive
      correlation was observed between IAB (> or = 120 ms) and the mean mitral valve
      gradient (R = 0.3, p <0.001). A strong negative correlation was also present
      between the mitral valve area (MVA) and the presence of IAB (R = -0.3, p <0.001).
      The presence of pulmonary hypertension and a poor NYHA functional class were
      associated with a high incidence of significant IAB (R = 0.4, p <0.001; R = 0.3,
      p <0.001, respectively), and there was a strong correlation between IAB and the P
      terminal force (p <0.001). Both, the presence of significant IAB and P-terminal
      force were correlated with a calcific mitral valve (p <0.001). Only the MVA (beta
      = 0.3; p = 0.008) was a predictor of IAB in multivariate analysis. CONCLUSION: A
      severe mitral gradient, a decreased MVA, an increased pulmonary artery pressure,
      and a poor NYHA class were shown to correlate with IAB duration and P-terminal
      force. Significant IAB (> or = 120 ms) and P-terminal force might be considered
      as a novel indicator of echocardiographic severity and associated complications
      during the follow up of MS. However, these interrelations must be clarified in
      further studies.

PMID- 22655491
TI  - Surgery for non-rheumatic calcific mitral stenosis.
AB  - During recent years there has been an increase in the referral pattern for
      surgery for non-rheumatic calcific mitral stenosis (CMS). Valve replacement for
      this condition presents some unique challenges, yet the management of CMS remains
      inadequately described. Herein are discussed the techniques and outcomes of
      surgery for CMS.

PMID- 22655492
TI  - Echocardiographic right ventricular function assessment before and after
      successful percutaneous mitral commissurotomy.
AB  - BACKGROUND AND AIM OF THE STUDY: In patients with mitral stenosis (MS), previous
      studies have shown discordant results with regards to improvements in right
      ventricular (RV) function immediately after percutaneous mitral commissurotomy
      (PMC). Hence, the study aim was to evaluate the impact of PMC on RV function, by
      using Doppler-echocardiography. METHODS: A total of 41 patients with severe
      symptomatic MS, in sinus rhythm, who had been referred to the authors'
      institution for PMC, was prospectively enrolled. A group of 25 healthy age- and
      gender-matched subjects served as controls. Transthoracic echocardiography (TTE)
      was performed on the day before and at 24/48 h after PMC. The RV function was
      evaluated using the Tricuspid Annular Plane Excursion (TAPSE), the RV Tei index,
      and systolic myocardial velocities by Doppler tissue imaging peak isovolumic
      contraction (DTI(IVC)) and peak systolic (DTI(S)) at the lateral tricuspid
      annulus). RESULTS: All patients but three underwent a successful PMC. The mitral
      valve area (MVA) was significantly increased (1.8 +/- 0.3 versus 1.1 +/- 0.2 cm2,
      p <0.0001), while the mean gradient (5 +/- 2 versus 10 +/- 7 mmHg, p <0.0001) and
      systolic pulmonary artery pressure (40 +/- 10 versus 54 +/- 21 mmHg, p = 0.0002)
      were decreased. Compared to healthy controls, the RV dysfunction in MS patients
      was authenticated by the DTI(IVC) and the Tei index (8.4 +/- 3.0 versus 11.1 +/-
      2.1 cm/s, p = 0.0002 and 0.33 +/- 0.10 versus 0.18 +/- 0.10 respectively, p
      <0.0001), but not by DTI(S) (12.9 +/- 3 versus 12.3 +/- 1.5 cm/s, p = 0.35) or
      TAPSE (24 +/- 5 versus 23 +/- 3 mm, p = 0.50). After PMC, no significant change
      regarding RV function was observed (TAPSE: 24 +/- 5 versus 24 +/- 5 mm, p = 0.54;
      Tei Index: 0.33 +/- 0.10 versus 0.36 +/- 0.12, p = 0.20; DTI(IVC): 8.4 +/- 3.0
      versus 9.2 +/- 3.4 cm/s, p = 0.08 and DTI(S): 12.9 +/- 3.0 versus 13.0 +/- 3.4
      cm/s, p = 0.54). CONCLUSION: The DTI(IVC) and Tei index appear to serve as the
      more sensitive indices of RV dysfunction in patients with MS. Immediately after a
      successful PMC, no significant change in Doppler echocardiographic parameters of
      RV function was observed. Whether late improvement in RV function can be
      observed, and the prognostic value of these parameters realized, deserve further
      investigation.

PMID- 22655493
TI  - The combined impact of postoperative heart failure and EuroSCORE on long-term
      outcome after surgery for aortic stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: Although the EuroSCORE was developed for
      predicting operative mortality after cardiac surgery, it has also been shown to
      predict long-term mortality. It has been reported that postoperative heart
      failure (PHF) in association with surgery, albeit comparatively benign in the
      short term, has a profound impact on five-year survival after surgery for aortic
      stenosis (AS). The study aim was to determine the combined impact of EuroSCORE
      and PHF on long-term survival after isolated aortic valve replacement (AVR) for
      AS. METHODS: A total of 397 patients (48% females; average age 70 +/- 10 years)
      who underwent AVR for AS at the authors' institution between 1995 and 2000 was
      studied. The cohort was subdivided according to the additive EuroSCORE into a
      high-risk group (EuroSCORE >7) and a low-risk group (EuroSCORE < or = 7), and
      further analyzed in relation to PHF. RESULTS: The average follow up was 8.1 years
      (range: 5.2-11.2 years). Forty-five patients (11%) were treated for procedure
      associated PHF. Patients with or without PHF and a high-risk EuroSCORE had crude
      five-year survivals of 57% and 64%, respectively (p = 0.6), whereas those with or
      without PHF but with a low-risk EuroSCORE had crude five-year survivals of 58%
      and 89%, respectively (p = 0.0003). CONCLUSION: Both PHF and a high EuroSCORE
      were associated with poor long-term survival. The role of PHF per se for the long
      term prognosis was illustrated by the fact that the negative impact on long-term
      survival was almost as profound in patients of the low-risk group as of the high
      risk group.

PMID- 22655494
TI  - One-year observation of inflammatory markers in patients with aortic valve
      stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to conduct an annual
      evaluation of plasma levels of C-reactive protein (CRP), tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6) and antibodies against Chlamydia
      pneumoniae during a 12-month period following the natural course of aortic valve
      stenosis (AVS). METHODS: A total of 60 patients with AVS and 14 control subjects
      underwent echocardiographic examinations at the start of the study period, and
      again after a 12-month follow up period. Subsequently, the AVS patients were
      allocated retrospectively to two groups (n = 30 in each) according to their
      echocardiographic parameters: patients who showed a progressive deterioration of
      valvular function (PAVS group); and those who showed a lack of such progression
      (LPAVS group). Plasma concentrations of CRP, TNF-alpha, IL-6, and antichlamydial
      IgA, IgG, and IgM antibodies were evaluated at the start of the study, and again
      during the 12th month. RESULTS: During the study, CRP levels were increased only
      in the AVS group. TNF-alpha and IgM levels were higher in the AVS group compared
      to controls, at both the initial visit and the final observation. During the 12
      month observation period the TNF-alpha level was increased in the PAVS group,
      whereas CRP levels in the LPAVS group were decreased. TNF-alpha levels were
      higher in the PAVS group than the LPAVS group, at both the initial visit and
      after 12 months; CRP levels did not differ between these groups. In the PAVS
      group, the IL-6 level was higher after 12 months, but the IgM level was higher at
      the initial visit. The results of a factorial analysis identified the main
      factors responsible for the decrease in aortic valve area to be TNF-alpha and
      CRP. CONCLUSION: TNF-alpha, CRP, and IgM antichlamydial antibodies should be
      further investigated as potential predictive factors for the progression of AVS.

PMID- 22655495
TI  - Mini-sternotomy aortic valve replacement: is it safe and effective? Comparison
      with standard techniques.
AB  - BACKGROUND AND AIM OF THE STUDY: Mini-sternotomy aortic valve replacement (MSAVR)
      has been increasingly performed at the authors' institution since October 2003.
      The study aim was to compare results obtained with MSAVR to those following AVR
      with conventional sternotomy (SAVR). METHODS: Between 1998 and 2008, a total of
      143 consecutive patients (mean age: 67 +/- 12.5 years) underwent AVR at the
      authors' institution. Of these patients, 82 underwent SAVR, and 61 underwent
      MSAVR performed through a reversed-L-shaped median sternotomy with a transverse
      limb at the right fourth intercostal space. Ascending aortic and right atrial
      cannulation through the mini-sternotomy were employed for cardiopulmonary bypass
      (CPB). RESULTS: Typically, the MSAVR patients were slightly younger than SAVR
      patients (mean age: 67 +/- 16 years and 70 +/- 15 years, respectively; p =
      0.037), had a lower incidence of diabetes (3% versus 18%, p = 0.008), and a
      slightly higher left ventricular ejection fraction (74.5 +/- 12% versus 71 +/-
      12%, p = 0.019). There were no other inter-group preoperative differences. As
      expected, MSAVR required a slightly longer aortic cross-clamp time (49 +/- 19
      min) compared to SAVR (44.5 +/- 16 min; p = 0.019), and longer CPB times (77 +/-
      31 min versus 60 +/- 26 min; p <0.0001), though the overall operating times were
      similar (p = 0.38). Postoperatively, MSAVR patients were extubated at 3 +/- 5 h,
      similar to SAVR patients (4 +/- 5 h) (p = 0.13). The median intensive therapy
      unit stay was 1 +/- 1 days in both groups. The median hospital stay was
      comparable between groups (MSAVR, 7 +/- 5 days; SAVR, 8 +/- 4 days; p = 0.48).
      The MSAVR patients had a higher incidence of delayed pericardial effusions
      requiring pericardiocentesis (n = 4; p = 0.031), but this did not affect
      survival. The 30-day mortality was similar in both groups (MSAVR group, n = 1
      (1.6%); SAVR group, n = 3 (3.7%); p = 0.64). At five years after surgery, freedom
      from cardiac-related death was 96 +/- 2.6% in MSAVR patients, and 89 +/- 4.9% in
      SAVR patients (p = 0.32). CONCLUSION: Mini-sternotomy AVR is technically
      challenging with longer CPB and aortic cross-clamp times. However, with
      increasing surgical experience, it offers results comparable to those achieved
      with conventional AVR, and with acceptable cosmetic results.

PMID- 22655496
TI  - Simulation of functional tricuspid regurgitation using an isolated porcine heart
      model.
AB  - BACKGROUND AND AIM OF THE STUDY: The results of tricuspid annuloplasty to treat
      functional tricuspid regurgitation (FTR) are sometimes suboptimal, and
      alternative techniques are needed. In the absence of reliable FTR models, and in
      an effort to minimize the need for animal experiments, a reproducible bench-model
      was developed of FTR, that allowed the simulation of the anatomic features of the
      condition. METHODS: A fresh porcine heart was mounted on a rigid support that was
      placed into a basin filled with saline; a closed circuit was then created with a
      centrifugal pump, equipped with connection tubes. The inflow tube of the pump
      conveyed saline from the basin to the pump; the outflow cannula was inserted
      through the pulmonary artery, across the pulmonary valve, into the right
      ventricle. The pump was activated to pressurize the right ventricle, thus
      inducing tricuspid valve regurgitation (TVR). The regurgitant flow through the
      valve was quantified using a flow-meter. Radiopaque markers were sutured to the
      head of each papillary muscle and to the tricuspid annulus, in order to trace the
      geometric changes of the tricuspid valve at increasing pump rates, using
      fluoroscopy. The efficacy of the bench-model was validated with 10 hearts.
      RESULTS: The TVR was increased proportionally with the right ventricular pressure
      (RVP) (TVR = 0.089xRVP - 1.515; R2 = 0.89). The increase in TVR was associated
      with increases in the annular-to-papillary muscles distance (APML) (TVR =
      0.059xAPML - 2.94; R2 = 0.96), of the inter-papillary muscles distance (PMD) (TVR
      = 0.058xPMD - 8.58; R2 = 0.94), and of the triscuspid annular dilatation (TAD)
      (TVR = 0.05xTAD - 1.85; R2 = 0.89). Of these parameters, APML was the strongest
      predictor of TVR. CONCLUSION: The porcine heart bench model represents a
      reproducible system to simulate the physiopathology of FTR, and has the potential
      to serve as a complementary method for the evaluation of new 'in vitro'
      technologies and therapies for FTR.

PMID- 22655497
TI  - Importance of shear in prosthetic valve closure dynamics.
AB  - BACKGROUND AND AIM OF STUDY: The results of recent hematological studies have
      suggested that, under non-physiological flow conditions, circulating procoagulant
      proteins activate the coagulation cascade. In the present study, in-vitro
      estimates of flow transients at or near the time of valve closure, including
      regional backflow velocity (RBV, m/s), flow acceleration (m/s2), and rate of
      acceleration (jerk, m/s3), have shed new light on the blood-damage potential of
      prosthetic valves. METHODS: Several prosthetic valves were tested in a pulse
      duplicator under simulated cardiac conditions. A unique prototype subsystem
      (Leonardo(VSI)) was used to measure the projected dynamic valve areas (PDVAs)
      from backlit valves. The regional flow velocity was derived by dividing the time
      dependent volumetric flow rate by the PDVA. The flow acceleration and jerk were
      subsequently obtained as time derivatives of the flow velocity. RESULTS: Current
      mechanical valves have overt flow transients at valve closure, relating to
      leaflet nonresponse to flow deceleration and residual PDVA. In contrast, tissue
      valves initiate closure during the flow deceleration phase, and seal when closed,
      thus preventing supra-physiological backflow transients. The estimated average
      RBV transients at or near closure ranged from 45 to 162 m/s for mechanical
      valves, and from 3 to 10 m/s (i.e., ca. 93% less) for tissue valves. The average
      derived flow acceleration and jerk transients ranged from +2,235 to -1,786xg and
      from +10.8 x 106 to -7.5 x 10(6) m/s3 for mechanical valves, respectively, and
      were substantially lower for tissue valves (ca. 90-99% less). CONCLUSION: The
      study results implicate that RBV transients at or near mechanical valve closure,
      and not the forward or closed flow phase, as being primary to the shear-induced
      activation of the coagulation cascade. Results obtained in vitro for an
      experimental trileaflet mechanical valve (Triflo) were tested only in the aortic
      site similar to those obtained with tissue valves.

PMID- 22655498
TI  - Risk factors for valve-related complications after mechanical heart valve
      replacement in 505 patients with long-term follow up.
AB  - BACKGROUND AND AIM OF THE STUDY: Currently, valve thrombosis, thromboembolic
      events and bleeding events account for 75% of all complications that occur after
      mechanical heart valve replacement. The study aim was to determine the main risk
      factors for valve-related complications in patients undergoing mechanical heart
      valve replacement. METHODS: Data were available from the systematic follow up of
      patients who had received a CarboMedics bileaflet mechanical heart valve
      replacement at the authors' institution. Follow up examinations were conducted
      prospectively at two-year intervals, via questionnaires sent to the patients'
      general practitioners, or by telephone calls. RESULTS: Between January 1988 and
      December 2005, a total of 505 consecutive patients (300 males, 205 females; mean
      age 52 years; range: 5 to 77 years) underwent heart valve replacement using a
      CarboMedics mechanical prosthesis. Aortic valve replacement (AVR) was performed
      in 308 patients, mitral valve replacement (MVR) in 134 patients, and double-valve
      replacement (DVR) in 62 patients. The follow up was 95.4% complete; the mean
      follow up was 7.5 years, and the total follow up 3,718 patient-years.
      Thromboembolic and bleeding complications represented the leading cause of valve
      related events (104/195), of valve-related mortality (15/25), and of the need for
      repeat surgery (9/16). Valve thrombosis occurred in 12 patients. Implantation in
      the mitral position was identified as a risk factor (HR = 15.07; CI: 8.41-23.07;
      p 0.0001). Thromboembolism occurred in 32 patients; the use of antiplatelet
      agents was found to be a protective factor (HR = 0.23; CI: 0.08-0.70; p = 0.01).
      Bleeding events occurred in 52 patients; risk factors for bleeding events
      included a history of thromboembolic or bleeding complications (HR = 2.70; CI:
      1.33-5.26; p = 0.006) and an unstable International Normalized Ratio (INR) (HR =
      2.86; CI: 1.01-8.08; p = 0.05). CONCLUSION: After mechanical heart valve
      replacement, the only risk factors for bleeding complications were an unstable
      INR and a history of thromboembolic or bleeding events. The use of antiplatelet
      agents proved to be a protective factor against thromboembolic events.

PMID- 22655499
TI  - Ten-year follow up after prospectively randomized evaluation of stentless versus
      conventional xenograft aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: The aim of this prospectively randomized study
      was to analyze the long-term clinical results after stentless versus conventional
      aortic valve replacement (AVR). METHODS: Between March 1996 and April 1998, a
      total of 225 patients was prospectively included into the study. Of these
      patients, 130 received a stentless aortic valve (SAV), and 95 a conventional
      stented bioprosthesis (CSB). In these patient groups, 95% and 96%, respectively,
      had an aortic stenosis, and the mean ages were 71 +/- 7 and 74 +/- 4 years,
      respectively. There were no significant inter-group differences in left
      ventricular function, preoperative pressure gradient, or NYHA functional status,
      and the aortic annulus diameter indices were comparable (13.5 mm in SAV patients
      versus 13.6 mm in CSB). Larger SAVs were implanted by using an oversizing
      technique. RESULTS: The 10-year follow up was 98% complete (mean follow up 102 +/
      48.5 months). At follow up the mean NYHA class was 1.7 +/- 0.8 after SAV versus
      1.9 +/- 0.7 after CSB, the left ventricular ejection fraction was 61 +/- 11%
      versus 60 +/- 8%, and the maximum aortic valve pressure gradient 19.4 +/- 8.7
      mmHg versus 24.7 +/- 7.7 mmHg (p = 0.03). The 10-year survival was 54 +/- 4.4%
      (SAV) versus 46 +/- 5.1% (CSB) (p = NS). In a subanalysis to obtain age-matched
      patient samples, the 10-year survival was 64 +/- 4.9% after SAV versus 46 +/-
      5.1% after CSB (p = 0.02). Among the surviving patients, 78% were satisfied with
      the procedure because of an improved ability to perform their daily activities,
      and an improved quality of life. CONCLUSION: A good functional and hemodynamic
      outcome was observed at 10 years after xenograft AVR. Stentless AVR was
      associated with a trend to a better survival; however, a regression of left
      ventricular hypertrophy occurred in all patients after AVR.

PMID- 22655500
TI  - Pulmonary homograft morphology after the Ross procedure: a computed tomography
      study.
AB  - BACKGROUND AND AIM OF THE STUDY: In patients undergoing the Ross procedure the
      autograft morphological characteristics have been well studied, but those of the
      homograft are less clear. The study aim was to describe the radiomorphological
      homograft characteristics in Ross patients, and to compare them with such
      characteristics in normal (control) subjects. METHODS: A total of 79 Ross
      patients (68 males, 11 females; mean age 43 +/- 12.3 years) underwent a computed
      tomography (CT) scan at a mean of 31 +/- 26 months after surgery. A group of 123
      patients without cardiovascular disease served as controls. Cryopreserved
      homografts were implanted in all Ross patients, with the majority being obtained
      from a single source. RESULTS: The mean donor age was 47 +/- 11 years, and the
      mean homograft diameter 25.4 +/- 1.3 mm (as provided at source).
      Electrocardiographic-gated CT reconstructions were used for the measurements. The
      smallest diameters were at the proximal anastomosis, and maximum diameters at the
      distal anastomosis (p <0.001). In controls, the minimum diameter was just
      proximal to the pulmonary valve annulus. In Ross patients, the homograft
      diameters were significantly smaller at all levels compared to controls. This
      effect persisted after taking into consideration patient age, height, gender,
      body surface area, and time since surgery. Notably, the measured homograft
      diameters were significantly smaller than those provided at source. CONCLUSION:
      The study results provided evidence of homograft shrinkage at all levels after
      the Ross procedure but, most prominently, at the level of the proximal suture
      line. This may have implications for novel preservation methods, as well as
      homograft size selection and implantation techniques.

PMID- 22655501
TI  - European multicenter study with the Soprano valve for aortic valve replacement:
      one-year clinical experience and hemodynamic data.
AB  - BACKGROUND AND AIM OF THE STUDY: During recent years, pericardial bioprostheses
      have gained widespread acceptance as cardiac valve substitutes. The study aim was
      to evaluate the early clinical and hemodynamic performance of the Sorin SopranoTM
      supra-annular aortic bioprosthesis, as used for aortic valve replacement (AVR).
      METHODS: Between January 2004 and August 2006, a total of 501 patients (55%
      males; mean age 75 +/- 6.4 years) was prospectively enrolled into the study,
      which involved 10 European institutions. The indications for AVR were aortic
      stenosis in 91% of patients, aortic incompetence in 8%, and redo surgery in 1%.
      Preoperatively, 62% of the patients were in NYHA class III, and 12% in class IV.
      The mean prosthesis size was 21.4 +/- 1.8 mm. A non-everting technique was used
      in 88% of patients. Concomitant procedures were performed in 52% of cases (mainly
      coronary artery bypass grafts; 41%). The mean cross-clamp and cardiopulmonary
      bypass times were 70 +/- 27.2 min and 99 +/- 39.7 min, respectively. Doppler
      echocardiography performed at one and 12 months after surgery was evaluated by an
      independent core laboratory. RESULTS: Postoperatively, there were 25 early deaths
      (5%) and 13 late deaths, with an overall survival at one year of 92.9% (95% CI:
      90.2-94.8) and freedom from valve-related death of 98.6% (95% CI: 97.5-99.6).
      After 12 months, most patients (87%) were in NYHA classes I-II. Actuarial
      freedoms from thromboembolism, bleeding, endocarditis and paraprosthetic leak at
      one year were 97.1% (CI: 95.1-98.2), 98.9% (CI: 97.4-99.5), 99.1% (CI: 97.7
      99.7), and 99.6% (CI: 98.3-99.9), respectively. No events of thrombosis and
      structural valve deterioration (SVD) were observed. Subsequent echocardiographic
      evaluation showed low mean (11.1 +/- 5.1 mmHg at one year) and peak (19.5 +/- 8.9
      mmHg at one year) transvalvular gradients, and a significant reduction in left
      ventricular mass, from 211 +/- 78.5 g at one month to 185 +/- 64.7 g at 12 months
      (p <0.0001). CONCLUSION: After 12 months, the clinical outcome with the Soprano
      bioprosthesis, when used for AVR, was excellent. The bioprosthesis also showed
      good hemodynamic performance, with a significant reduction of left ventricular
      hypertrophy.

PMID- 22655502
TI  - The Freedom SOLO valve: mid-term clinical results with a stentless pericardial
      valve for aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the Freedom SOLO
      pericardial stentless valve prosthesis implanted in a subcoronary or supra
      annular position, using a single running suture, over a follow up period of up to
      five years. The clinical data obtained after aortic valve replacement (AVR) were
      analyzed retrospectively for validation. METHODS: Between April 2004 and
      September 2009, a total of 143 patients (81 males, 62 females; mean age 71 +/- 7
      years; range: 41-87 years) underwent primary AVR using the Freedom SOLO valve,
      implanted with a supra-annular subcoronary technique. Isolated AVR was performed
      on 120 patients, while 23 patients required additional surgery that included
      coronary artery bypass grafting (n = 5), ascending aorta replacement (n = 1),
      atrial fibrillation surgery (n = 9), and mitral valve repair (n = 1). Clinical
      investigations were performed before, during and after surgery; the follow up was
      100% complete. A subgroup of patients (70%) was investigated
      echocardiographically during the follow up period to analyze the hemodynamic
      performance of the prosthesis. RESULTS: For all procedures the mean ischemia time
      was 66 +/- 15 min, and the mean cardiopulmonary bypass (CPB) time 88 +/- 20 min.
      For isolated AVR, the mean cross-clamp time was 65 +/- 14 min, and the mean CPB
      time 85 +/- 17 min. The predominant implanted valve size was 25 mm (42%).
      Operative mortality was 4.9% (7/143), with an overall mortality of 10.5% (15/143)
      at 4.7 years of follow up. The mean follow up was 1.8 +/- 1.4 years, and the
      total follow up 257 patient-years. At postoperative follow up the mean valve
      gradient was 10.6 mmHg, while the effective orifice area was 1.9 +/- 0.6 cm2 at
      one month and 1.9 +/- 0.6 cm2 at 12 months. CONCLUSION: The Freedom SOLO valve
      was implanted in a cohort of patients, using a simplified, supra-annular
      subcoronary technique, with no technical problems. Subsequently, the valve
      demonstrated an excellent clinical performance for up to five years. Further long
      term follow up will be required to confirm the performance of the prosthesis with
      regards to structural and nonstructural valve stability.

PMID- 22655503
TI  - Transapical aortic valve implantation and 'off-pump' arterial coronary bypass in
      a patient with a porcelain aorta.
AB  - A simple hybrid procedure, namely transapical aortic valve implantation combined
      with 'off-pump' coronary artery bypass using an internal thoracic artery, was
      performed in a patient with porcelain aorta, aortic valve stenosis and coronary
      artery disease. This approach does not require cardiopulmonary bypass, and avoids
      aortic or peripheral arterial cannulation and clamping of the aorta. This hybrid
      approach can be regarded as a 'new technique' being applied to an 'old idea'.

PMID- 22655504
TI  - Aortic valve 'kissing' vegetation: mitral valve endocarditis with functional
      aortic stenosis.
AB  - The case is reported of giant mitral valve vegetation that was wedged into the
      aortic valve plane (aortic valve 'kissing' vegetation), causing obstruction to
      the left ventricular outflow tract. In such a case, echocardiography plays a key
      role in the assessment of vegetation morphology, risk of embolization, impact on
      valvular function and indication for surgery. Because of its size, the
      obstructive hemodynamics, and the potential to induce aortic valve endocarditis,
      aortic 'kissing' vegetation requires surgical intervention to preserve the
      integrity of the valve and improve the hemodynamic status.

PMID- 22655505
TI  - Post-traumatic blunt mitral insufficiency: surgical experience and review.
AB  - Three cases of acute mitral insufficiency after blunt chest trauma are presented.
      All three patients underwent urgent surgery for mitral valve replacement (MVR).
      The first patient presented complete detachment of the anterior papillary muscle,
      while the other two showed rupture of the posterior papillary muscle. The second
      patient also suffered rupture of the anterior papillary muscle of the tricuspid
      valve, and subsequently underwent double mitral-tricuspid valve replacement. All
      patients survived the operation and were discharged in good condition. An
      extensive review of the literature on surgically managed patients is included. In
      this group of high-risk patients, MVR represents a rapid and safe operation, and
      represents a good surgical option.

PMID- 22655506
TI  - Type A quadricuspid aortic valve and ascending aorta aneurysm: a rare
      combination.
AB  - Quadricuspid aortic valve (QAV) is a rare congenital anomaly associated with
      aortic valve insufficiency and significant morbidity, and requires the
      replacement or, rarely, the repair of the malfunctioning heart valve. A QAV
      associated with an ascending aorta aneurysm is an extremely rare anatomic
      combination with a hypothetical, but not clear, shared embryological etiology. To
      date, only two cases of type B QAV with ascending aorta aneurysm have been
      reported. Herein is described the first ever case of a 38-year-old male suffering
      from severe symptomatic aortic valve regurgitation due to a type A QAV,
      associated with an ascending aorta aneurism, who underwent a successful combined
      replacement of the aortic valve and ascending aorta.

PMID- 22655507
TI  - Textile heart valve: first implantation in vivo.

PMID- 22655508
TI  - Image of the month. Double-orifice mitral valve with bicuspid aortic valve.

PMID- 22655509
TI  - Symptomatic therapy of Duchenne muscular dystrophy (DMD).

PMID- 22655510
TI  - Drug treatment of Duchenne muscular dystrophy: available evidence and
      perspectives.
AB  - Duchenne muscular dystrophy (DMD) is a disease linked to the X-chromosome which
      affects 1 in 3,600-6,000 newborn males. It is manifested by the absence of the
      dystrophin protein in muscle fibres, which causes progressive damage leading to
      death in the third decade of life. The only medication so far shown to be
      effective in delaying the progression of this illness are corticosteroids, which
      have been shown to increase muscle strength in randomised controlled studies;
      long-term studies have demonstrated that they prolong walking time and retard the
      progression of respiratory dysfunction, dilated cardiomyopathy and scoliosis.
      Several potential drugs are now being investigated. Genetic therapy, involving
      the insertion of a dystrophin gene through a vector, has proven effective in
      animals but not humans. Currently under clinical study is Ataluren, a molecule
      that binds with ribosomes and may allow the insertion of an aminoacid in the
      premature termination codon, and exon-skipping, which binds with RNA and excludes
      specific sites of RNA splicing, producing a dystrophin that is smaller but
      functional. There are also studies attempting to modulate other muscular
      proteins, such as myostatin and utrophin, to reduce symptoms. This paper does not
      address cardiomyopathy treatment in DMD patients.

PMID- 22655511
TI  - Old and new therapeutic developments in steroid treatment in Duchenne muscular
      dystrophy.
AB  - Steroids have been used since two decades and several trials were conducted to
      establish their efficacy in DMD patients with various regimens. The clinical
      outcomes showed increased function in the treated boys, and in a single trial
      with deflazacort, prolongation of ambulation but with different side effects.
      Steroids clinical efficacy is now established. The main concern is to increase
      steroid efficacy and decrease side effect and toxicity. A trial comparing daily
      prednisone, deflazacort and intermittent glucocorticoids (prednisone 10 days
      on/10 days off) (FOR-DMD) is starting under NIH grant. The primary outcomes will
      be muscle strength, forced vital capacity and patient/parents satisfaction.

PMID- 22655512
TI  - The Canadian experience with long-term deflazacort treatment in Duchenne muscular
      dystrophy.
AB  - Deflazacort is the most commonly prescribed corticosteroid for the treatment of
      Duchenne muscular dystrophy in Canada. We review the long-term experience with
      deflazacort treatment at two centers in Canada; Montreal and Toronto. Deflazacort
      has benefitted both cohorts by prolonged ambulation, preserved cardiac and
      respiratory function, less scoliosis and improved survival. Common side effects
      in both cohorts include weight gain, decreased height and cataract formation. The
      Canadian experience supports the use of deflazacort in treating boys with
      Duchenne muscular dystrophy.

PMID- 22655513
TI  - Surgical treatment of Duchenne muscular dystrophy patients in Germany: the
      present situation.
AB  - In 1988, we familiarised ourselves at Poitiers with the concept of operative
      treatment of the lower limbs and the spine in Duchenne muscular dystrophy (DMD)
      patients which Yves Rideau and his collaborators had developed there in the early
      1980s. Thereupon, we immediately established the techniques at our home
      universities, first at the Technische Universitat Aachen and, from 1999 on, at
      the Universitatsklinikum Erlangen, Germany. Since then, we have applied the
      technique to more than 500 DMD patients in total by performing more than 800
      operations on the lower limbs and/or spine. In support of findings reported by
      Professor Rideau in this issue we observed that, where patients are still
      ambulatory at the time of operation, the operation delays the point at which
      patients become wheelchair-bound by about two years. Likewise, patients receiving
      this treatment were/are also able to perform the Gowers' manoeuvre for around two
      years longer.

PMID- 22655514
TI  - Treatment of dystrophinopathic cardiomyopathy: review of the literature and
      personal results.
AB  - Cardiomyopathy is an almost universal finding in boys affected by Duchenne
      muscular dystrophy (DMD). Myocardial changes, as a result of the lack of
      dystrophin, consist of cell membrane degradation, interstitial inflammation,
      fatty replacement and fibrosis. Dystrophinopathic cardiomyopathy generally starts
      as a preclinical or intermediate stage, with evolution toward advanced stages
      characterized by ventricle enlargement but also by symptoms and signs of heart
      failure (dyspnoea, peripheral edema and liver enlargement). However in few
      patients the dilation could be the first manifestation of the heart involvement.
      The ability to detect overt cardiomyopathy increases with age, such that more
      than 80% of boys older than 18 years will have abnormal systolic function.
      Several drugs have been employed with the aim to contrast the evolution of
      cardiomyopathy toward stages of severe congestive heart failure. A review of
      cardiac treatment in DMD and personal experience are reported and discussed.

PMID- 22655515
TI  - Rationale for treating oedema in Duchenne muscular dystrophy with eplerenone.
AB  - Recently we reported a cytoplasmic sodium overload to cause a severe osmotic
      oedema in Duchenne muscular dystrophy (DMD). Our results suggested that this dual
      overload of sodium ions and water precedes the dystrophic process and persists
      until fatty muscle degeneration is complete. The present paper addresses the
      questions as to whether these overloads are important for the pathogenesis of the
      disease, and if so, whether they can be treated. As a first step, we investigated
      the effects of various diuretic drugs on a cell model of DMD, i.e. rat diaphragm
      strips previously exposed to amphotericin B. We found that both carbonic
      anhydrase inhibitors and aldosterone antagonists were able to repolarise
      depolarised muscle fibres. Since carbonic anhydrase inhibitors are known to have
      acidifying effects and this might be detrimental to the ventilation of DMD
      patients, we mainly concentrated on the modern spironolactone derivative,
      eplerenone. This drug had a very high repolarizing power, the parameter
      considered by us as being most relevant for a beneficial effect. In a pilot study
      we administered this drug to a 22-yr-old female DMD patient who was bound to an
      electric wheelchair and has had no corticosteroid therapy before. Eplerenone
      decreased both cytoplasmic sodium and water overload and increased muscle
      strength and mobility. We conclude that eplerenone has beneficial effects on DMD
      muscle. In our opinion the cytoplasmic oedema is cytotoxic and should be treated
      before fatty degeneration takes place.

PMID- 22655517
TI  - Requiem.
AB  - "In never considering neuromuscular disease to be untreatable, Yves Rideau has
      found ways to ameliorate every aspect of these conditions. His work has resulted
      in immeasurably enhancing the quality of life of his patients". This dedication
      included into the Guide to Evaluation in Management of Neuromuscular Diseases,
      1999, made by a coworker who studied in Poitiers from 1981 to 1983, summarizes
      the content of this paper.

PMID- 22655516
TI  - Pre-clinical drug tests in the mdx mouse as a model of dystrophinopathies: an
      overview.
AB  - Duchenne muscular dystrophy is a lethal X-linked muscle disease affecting 1/3500
      live male birth. It results from defects in the subsarcolemmal protein
      dystrophin, a component of the dystrophin-glycoprotein complex (DGC) which links
      the intracellular cytoskeleton to the extracellular matrix. The absence of
      dystrophin leads to muscle membrane fragility, muscle necrosis and gradual
      replacement of skeletal muscle by fat and connective tissue, through a complex
      and still unclear cascade of interconnecting events. No cure is currently
      available, with glucocorticoids being the sole drugs in clinical use in spite of
      their remarkable side effects. A great effort is devoted at performing pre
      clinical tests on the mdx mouse, the mostly used homologous animal model for DMD,
      with the final aim to identify drugs safer than steroids and able to target the
      pathogenic mechanisms so to delay pathology progression. This review updates the
      efforts on this topic, focusing on the open issues about the animal model and
      highlighting the classes of pharmaceuticals that are more promising as disease
      modifiers, while awaiting for more corrective therapies. Although caution is
      necessary in data transfer from mdx model to DMD patients, the implementation of
      standard operating procedures and the growing understanding of the pathology may
      allow a more accurate evaluation of therapeutics, alone or in combination, in pre
      clinical settings. A continuous cross-talk with clinicians and patients
      associations are also crucial points for proper translation of data from mouse to
      bedside.

PMID- 22655518
TI  - Risk factors for occupational injuries among full-time farmers in Finland.
AB  - The objectives of this study were to evaluate the frequency of and farm
      management-related risk factors for occupational injuries among full-time
      farmers. A computer-assisted telephone interview was conducted among randomly
      selected self-employed full-time farmers (n = 1182; 911 male and 271 female), The
      response rate was 86%. Two-thirds of the respondents raised dairy or beef cattle.
      Nearly 16% of the farmers had experienced one or more occupational injuries
      requiring medical consultation during the past 12 months; the total number of
      such injuries was 222. Injuries were more common among male (17 injuries/100
      person-years) than female farmers (13 injuries/ 100 person-years). The injuries
      occurred most frequently in animal husbandry work (n = 97). Falling or slipping
      was the most common mechanism of injury. Poisson regression with a stepwise
      (forward) model selection procedure identified the following risk factors for
      occupational injuries: male gender, younger age, cooperation with other farmers,
      perceived high accident risk, and stress symptoms. The adjusted rate ratios for
      these risk factors ranged from 1.40 to 1.96. This study indicates that
      interventions are needed, particularly among male farmers in their early years of
      full-time farm operation. At this stage of life, heavy financial burden and
      stress while establishing and expanding production may contribute to injuries. To
      reduce stress and related injuries, we recommend guidance for farmers regarding
      the organization and management of farm work.

PMID- 22655519
TI  - Ohio farm safety day camps: developing a successful statewide program through
      surveillance and evaluation.
AB  - To address the at-risk population of rural youth, Ohio State University Extension
      initiated a statewide farm safety day camp program, partnering with other state
      sponsors. The program has completed a ten-year anniversary, and evaluation data
      from the 79 camp sessions held within that timeframe (N = 15,440; response rate =
      79.4%) were analyzed. The objectives of the evaluation were to determine youth
      perceptions of their experience as well as determine if the camp sessions
      accurately targeted high injury-causing agents. Overall, 75.0% of the campers
      were satisfied with the program, 76.0% reported that they learned from their
      participation, and 71.2% agreed that the information was relevant and useful.
      Popular topics taught at the day camps were consistent with the most prevalent on
      farm injury hazards affecting youth populations, including livestock safety, ATV
      safety, lawn and garden safety, tractor and machinery safety, electrical safety,
      and water safety.

PMID- 22655520
TI  - Prominent barriers and motivators to installing ROPS: an analysis of survey
      responses from Pennsylvania and Vermont.
AB  - Tractor overturns contribute significantly to the number of work-related deaths
      that occur every year on U.S. farms. Although the agriculture, forestry, and
      fishing industries have the highest fatality rates of any industries, researchers
      predict that the elimination of tractor overturn fatalities could result in a
      noticeable reduction in the farm fatality rate. Rollover protection structures
      (ROPS) are 99% effective in preventing overturn fatalities. However, roughly 50%
      of U.S. tractors do not have a ROPS. In order to identify prominent barriers and
      motivators to installing ROPS, a phone survey was conducted with a random sample
      of farmers (n = 327) in Vermont and Pennsylvania, two states interested in
      developing ROPS installation programs. Results indicated that cost and perceived
      need were the most frequently highly rated barriers to ROPS installation in both
      states, while working near hills or ditches and concerns regarding liability were
      the most frequently highly rated motivators for installing ROPS. Additionally,
      older farmers identified limited use of a tractor as a highly rated barrier.

PMID- 22655521
TI  - Assessing farm tractor incidents and awareness levels of operators for tractor
      safety issues in the Hatay province of Turkey.
AB  - Studies and statistical data on safety issues related to farm tractors and
      machinery are very limited in developing countries, including Turkey. This study
      was carried out to investigate tractor-related incidents in the Hatay province,
      located in the mid-south of Turkey. A questionnaire was conducted with 107
      tractor operators using face-to-face interviews. Data were evaluated according to
      the incident type, machinery involved, and mechanism of injury or fatality. A
      total of 101 incidents were reported by 77 of the 107 respondents. Most of the
      incidents were due to tractor rollovers (65.4%), 14.8% of the incidents were due
      to entanglement of body parts in moving machinery, and 12.9% involved crashing
      into other vehicles or obstacles. The leading cause of the incidents was personal
      mistakes (60.4%). Fatalities resulted from 25.7% of the incidents, while 45.5% of
      the incidents caused non-fatal injuries. Only 5.6% of the tractors had a ROPS
      enclosed cab. The percentage of ROPS-equipped tractors was 19.6%, while 41.3% of
      the tractors had a shade cover and 33.6% had no protective structure. Only one of
      the respondents used a seatbelt, although 44.9% of them stated that seatbelts
      should be used. It was also found that only 13.5% of the operators had training
      in work safety, while 95.1% stated that incidents might be reduced if people were
      trained. Development of appropriate policies and training programs are needed for
      safer operation of agricultural machinery to reduce injuries and fatalities due
      to farm accidents.

PMID- 22655522
TI  - ROPS deficiency of gray-market tractors.
AB  - Many used tractors that are imported from Japan are adding to the current
      national inventory in the U.S. and Canada of farm tractors that lack a rollover
      protective structure (ROPS). Gray-market tractors are built for use by the
      manufacturer for a certain country but are imported against the manufacture's
      wishes to a second country for use there, usually as a used tractor. Gray-market
      tractors may lack ROPS and seatbelts, depending on the date of manufacturer. The
      objective of this investigation is to describe the gray market for tractors
      imported from Japan into the U.S. and the policy implications regarding the
      hazards associated with these imports. Operator manuals and warning labels are
      typically not written in English. Foreign manufacturers that market tractors in
      the U.S. have established a variety of disincentives for the importation of gray
      market tractors, including issuing warnings, not servicing or providing parts for
      these tractors, and banning their importation through actions by the U.S.
      International Trade Commission. Nonetheless, a U.S. market has developed that
      imports and provides services and parts for gray-market tractors, and some
      companies provide certified ROPS on the tractors that they sell. A product safety
      perspective and related policies are presented as an approach to ensuring that
      these imports are equipped with ROPS and seatbelts.

PMID- 22655523
TI  - Establishing the need for an engineering standard for agricultural hitch pins.
AB  - Documented incidents have occurred in which failure or unintentional
      disengagement of agricultural hitch pins has contributed to property damage and
      personal injury. An examination of current hitch pin use on a convenience sample
      of farm operations in Indiana revealed a variety of non-standard, worn and
      damaged, and inappropriately sized hitch pins in use. Informal interviews with
      the farm operators confirmed that hitch pin misuse, failure, or disengagement is
      a relatively widespread problem that remains largely unaddressed. On-site
      observations also suggested a low use of hitch pin retaining devices or safety
      chains. A review of prior research revealed that little attention has been given
      to this problem, and currently no documentation allows for an estimate of the
      frequency or severity of losses associated with hitch pin misuse, failure, or
      disengagement. No specific engineering standards were found that directly applied
      to the design, appropriate selection, or loading capacity of agricultural hitch
      pins. Major suppliers of replacement hitch pins currently provide little or no
      information on matching hitch pin size to intended applications, and most
      replacement hitch pins examined were of foreign origin, with the overwhelming
      majority imported from China or India. These replacement hitch pins provided no
      specifications other than diameter, length, and, in some cases, labeling that
      indicated that the pins had been "heat treated. " Testing of a sample of 11
      commercially available replacement hitch pins found variation along the length of
      the pin shaft and between individual pins in surface hardness, a potential
      predictor of pin failure. Examination of 17 commercially available replacement
      pins also revealed a variety of identifiers used to describe pin composition and
      fabrication methods, e.g., "heat treated." None of the pins examined provided any
      specifications on loading capacity. It was therefore concluded that there is a
      need to develop an agricultural hitch pin engineering standard that would reflect
      current agricultural applications and practices and that would be promoted to
      both original equipment manufacturers and manufacturers and suppliers of
      replacement hitch pins. The standard should address the design of composite pins,
      heat treating, surface hardening, loading capacity and labeling of such,
      incorporation of unintentional disengagement prevention devices, indicators of
      the need for replacement due to wear, and safety information that should be
      included in operator instructions. ASABE is the most appropriate organization to
      develop such a standard. It was also concluded that agricultural safety and
      health programs and professionals need to raise the awareness of farmers
      concerning the appropriate selection and use of agricultural hitch pins,
      including the need to replace non-standard pins with pins less likely to fail or
      disengage during use, the need to replace hitch pins with indications of
      potential failure, and the importance of using appropriate safety chains,
      especially during transport of equipment behind tractors and trucks on public
      roads.

PMID- 22655524
TI  - The information age, cyberspace, and cancer.

PMID- 22655525
TI  - Alpha particles as radiopharmaceuticals in the treatment of bone metastases:
      mechanism of action of radium-223 chloride (Alpharadin) and radiation protection.
AB  - Approximately 85% to 90% of men with castration-resistant prostate cancer (CRPC)
      have radiological evidence of bone metastases. To date, however, therapies to
      manage bone metastases have been primarily palliative. Among CRPC patients with
      bone metastases, there is a significant unmet need for active antitumor treatment
      options that are highly efficacious and have a favorable safety profile. This
      article will present current information about alpha-pharmaceuticals, a new class
      of targeted cancer therapy for the treatment of patients with CRPC and bone
      metastases. It will review preclinical and clinical studies of the experimental
      radiopharmaceutical radium-223 chloride (Alpharadin), a first-in-class, highly
      targeted and well-tolerated alpha-pharmaceutical under development to improve
      survival in patients with bone metastases from advanced prostate cancer.
      Alpharadin kills cancer cells via alpha radiation from the decay of radium-223, a
      calcium mimetic that naturally self-targets to bone metastases. The mechanism of
      action of Alpharadin and specifics of administration, radiation protection, and
      patient management will be discussed.

PMID- 22655526
TI  - Radium-223: down to the bone, and less is more.

PMID- 22655527
TI  - An alpha edge?

PMID- 22655528
TI  - Molecular profiling assays in breast cancer: are we ready for prime time?
AB  - Breast cancer is a heterogeneous disease with diverse morphologies, molecular
      characteristics, and clinical behavior. The advances in molecular profiling
      technologies have changed our understanding of breast cancer and led to the
      identification of prognostic/predictive gene signatures. Despite the huge
      quantity of information gleaned from these profiling technologies and the
      increasing number of gene signatures, their incorporation into clinical decision
      making is a slow process and is limited in various aspects. The 70-gene assay
      (MammaPrint, Agendia, Netherlands) and the 21-gene assay (Oncotype DX, Genomic
      Health, USA) are the most widely used breast cancer multigene classifier assays.
      A 50-gene assay (PAM50, NanoString, USA) has shown promise but needs further
      independent validation. In this review, we will present the current data on
      commercially available molecular profiling assays in breast cancer and discuss
      the challenges surrounding their incorporation into routine clinical practice as
      prognostic and predictive tools.

PMID- 22655529
TI  - Molecular profiling assays in breast cancer: beyond prime time and into
      syndication.

PMID- 22655530
TI  - A perspective on genomic tests for breast cancer: the need for progress.

PMID- 22655531
TI  - Multimodal approach to anaplastic thyroid cancer.
AB  - Despite more than 50 years of research, the overall clinical outcomes of patients
      afflicted with anaplastic thyroid cancer remain dismal. Survival is limited by
      the dire consequences of an uncontrolled primary and the prevalence of overt or
      occult distant metastasis. Local control is influenced by multiple confounding
      variables, including the inherent biological aggressiveness of the disease and
      the seemingly insurmountable technical obstacles to both surgery and
      radiotherapy. In response to these challenges, revolutionary changes in the
      treatment paradigm over the last 20 years, specifically the adoption of a
      multimodal treatment strategy, suggest improvements in local control and short
      term median survival and have changed the pattern of progression, even for
      patients presenting with locally advanced disease. For the first time there is
      attestation of even long-term survivorship for a few patients who harbor advanced
      local, but nonmetastatic, disease. The current challenge is to address the high
      incidence of apparent or occult distant metastasis. Newly developed targeted
      therapies are likely to change the treatment paradigm, and they hold the promise
      of being able eventually to make treatment with curative intent available to some
      patients.

PMID- 22655532
TI  - Toward improved outcomes in patients with anaplastic thyroid cancer.

PMID- 22655533
TI  - Time to change the treatment paradigms in anaplastic thyroid carcinoma.

PMID- 22655534
TI  - Synthesis of resins with ionic liquids for purification of flavonoids from
      Hippophae rhamnoides L. leaves.
AB  - The efficient purification method of high-purity flavonoids from  Hippophae
      rhamnoides  L. (sea buckthorn) is reported. A novel room temperature ionic liquid
      based macroporous adsorption resin (MAR), N-methylimidazole/MARs (Mim/MARs), was
      prepared on the basis of the Friedel-Crafts-catalyzed and surface-modified
      technique. The material exhibited favorable characteristics for adsorption
      application, including high pore volume (1.90 cm(3)/g, 3 times as big as the
      optimal commercial adsorbent), good pore structure (type IV isotherm with an H1
      hysteresis loop, the most favorable structure for adsorption purposes), narrow
      particle size and pore size distribution (1.2 mm with a standard deviation of
      0.106 mm), and excellent chemical stability. This paper also presents the first
      experimental evidence that the functional groups of the modified materials and
      composite action of certain molecular interactions between the adsorbent and
      flavonoids affected the adsorption process. Moreover, a new sphere-size
      adsorption kinetics model in which the adsorption process contained three or more
      compartments and detailed parameters of sphere size was developed according to
      the multicompartment kinetics model and Karichhoff's theory by investigating the
      regression of the experimental results. The conclusion that the first compartment
      of the adsorption process onto Mim/MARs mainly occurred on spheres larger than
      0.83 mm and the second and third ones mainly occurred on spheres of 0.46-0.83 and
      0.22-0.46 mm, respectively, was drawn from this new sphere-size adsorption
      kinetics model.

PMID- 22655535
TI  - Remote control catheter navigation: options for guidance under MRI.
AB  - BACKGROUND: Image-guided endovascular interventions have gained increasing
      popularity in clinical practice, and magnetic resonance imaging (MRI) is emerging
      as an attractive alternative to X-ray fluoroscopy for guiding such interventions.
      Steering catheters by remote control under MRI guidance offers unique challenges
      and opportunities. METHODS: In this review, the benefits and limitations of MRI
      guided remote control intervention are addressed, and the tools for guiding such
      interventions in the magnetic environment are summarized. Designs for remote
      control catheter guidance include a catheter tip electromagnetic microcoil
      design, a ferromagnetic sphere-tipped catheter design, smart material-actuated
      catheters, and hydraulically actuated catheters. Remote control catheter guidance
      systems were compared and contrasted with respect to visualization, safety, and
      performance. Performance is characterized by bending angles achievable by the
      catheter, time to achieve bending, degree of rotation achievable, and
      miniaturization capacity of the design. Necessary improvements for furthering
      catheter design, especially for use in the MRI environment, are addressed, as are
      hurdles that must be overcome in order to make MRI guided endovascular procedures
      more accessible for regular use in clinical practice. CONCLUSIONS: MR-guided
      endovascular interventions under remote control steering are in their infancy due
      to issues regarding safety and reliability. Additional experimental studies are
      needed prior to their use in humans.

PMID- 22655536
TI  - The relationship between localized subarachnoid inflammation and parenchymal
      pathophysiology after spinal cord injury.
AB  - Subarachnoid inflammation following spinal cord injury (SCI) can lead to the
      formation of localized subarachnoid scarring and the development of post
      traumatic syringomyelia (PTS). While PTS is a devastating complication of SCI,
      its relative rarity (occurring symptomatically in about 5% of clinical cases),
      and lack of fundamental physiological insights, have led us to examine an animal
      model of traumatic SCI with induced arachnoiditis. We hypothesized that
      arachnoiditis associated with SCI would potentiate early parenchymal
      pathophysiology. To test this theory, we examined early spatial pathophysiology
      in four groups: (1) sham (non-injured controls), (2) arachnoiditis (intrathecal
      injection of kaolin), (3) SCI (35-g clip contusion/compression injury), and (4)
      PTS (intrathecal kaolin+SCI). Overall, there was greater parenchymal inflammation
      and scarring in the PTS group relative to the SCI group. This was demonstrated by
      significant increases in cytokine (IL-1alpha and IL-1beta) and chemokine (MCP-1,
      GRO/KC, and MIP-1alpha) production, MPO activity, blood-spinal cord barrier
      (BSCB) permeability, and MMP-9 activity. However, parenchymal inflammatory
      mediator production (acute IL-1alpha and IL-1beta, subacute chemokines), BSCB
      permeability, and fibrous scarring in the PTS group were larger than the sum of
      the SCI group and arachnoiditis group combined, suggesting that arachnoiditis
      does indeed potentiate parenchymal pathophysiology. Accordingly, these findings
      suggest that the development of arachnoiditis associated with SCI can lead to an
      exacerbation of the parenchymal injury, potentially impacting the outcome of this
      devastating condition.

PMID- 22655579
TI  - [International opening of our Academy].

PMID- 22655578
TI  - Quantitative imaging of ion transport through single nanopores by high-resolution
      scanning electrochemical microscopy.
AB  - Here we report on the unprecedentedly high resolution imaging of ion transport
      through single nanopores by scanning electrochemical microscopy (SECM). The
      quantitative SECM image of single nanopores allows for the determination of their
      structural properties, including their density, shape, and size, which are
      essential for understanding the permeability of the entire nanoporous membrane.
      Nanoscale spatial resolution was achieved by scanning a 17 nm radius pipet tip at
      a distance as low as 1.3 nm from a highly porous nanocrystalline silicon membrane
      in order to obtain the peak current response controlled by the nanopore-mediated
      diffusional transport of tetrabutylammonium ions to the nanopipet-supported
      liquid-liquid interface. A 280 nm * 500 nm image resolved 13 nanopores, which
      corresponds to a high density of 93 nanopores/MUm(2). A finite element simulation
      of the SECM image was performed to assess quantitatively the spatial resolution
      limited by the tip diameter in resolving two adjacent pores and to determine the
      actual size of a nanopore, which was approximated as an elliptical cylinder with
      a depth of 30 nm and major and minor axes of 53 and 41 nm, respectively. These
      structural parameters were consistent with those determined by transmission
      electron microscopy, thereby confirming the reliability of quantitative SECM
      imaging at the nanoscale level.

PMID- 22655580
TI  - [Workplace testing of drugs of abuse and psychotropic drugs].
AB  - In France, workplace testing of drugs of abuse and psychotropic drugs is rarely
      performed; meanwhile it is a major public health problem. Furthermore, France is
      the European country that has been associated with the highest increase of the
      use of drugs of abuse, particularly cannabis. So workplace biological screening
      of drugs of abuse and of psychotropic drugs exposure is of major concern. New
      analytical techniques have been developed during the last years. The authors will
      consider analytical screening of drugs of abuse and particularly the comparison
      of analytical techniques applied to urine and saliva. The advantages and the
      disadvantages of these two matrices will be considered. Urinary and blood
      quantification will be reviewed, but also the interest of hair testing to explore
      chronic exposure. The research of psychotropic drugs in biological fluids is also
      a part of this paper. New analytical trends are promising and complete analysis
      of these substances will be soon routinely possible in blood using a single spot
      test.

PMID- 22655581
TI  - [Gout: an overview of available urate lowering therapies].
AB  - The aim of urate-lowering therapy is to maintain urate concentration below the
      saturation point for monosodium urate. This therapy dissolves crystal deposits
      and cures gout while it is maintained. EULAR guidelines recommend that plasma
      urate should be maintained at a concentration less than 360MUM, and the British
      Guidelines less than 300MUM. Urate-lowering therapy is indicated for patients
      with recurrent gout attacks, chronic arthropathy, tophi, and gout with uric acid
      stones. Allopurinol lowers uricemia through inhibition of xanthine oxidase
      activity. The maximum allowed dose is reduced in case of renal failure, which is
      relatively frequent in gouty patients. Febuxostat has been approved for the
      treatment of chronic hyperuricemia in conditions where urate deposition has
      already occurred. Febuxostat is a novel non-purine, selective inhibitor of
      xanthine oxidase, metabolized and excreted by the liver, so no dose adjustment
      appears to be necessary in patients with mild-to-moderate renal impairment.
      Another powerful hypo-uricemic drug is the PEG-uricase (pegloticase). Pegloticase
      is a uric acid-specific PEGylated recombinant mammalian uricase recently approved
      by the FDA for treatment of patients with refractory chronic gout.

PMID- 22655582
TI  - Long-term stability of bevacizumab repackaged in 1mL polypropylene syringes for
      intravitreal administration.
AB  - INTRODUCTION: The anti-angiogenic monoclonal antibody, bevacizumab, is currently
      used by intravitreal administration as off-label drug to treat age-related
      macular degeneration or other ophthalmologic diseases. For this purpose,
      commercial bevacizumab is repackaged in 1mL polypropylene syringes under sterile
      conditions. However, no complete study on the stability of this hospital-based
      preparation is available. METHODS: Commercial bevacizumab (25mg/mL; Avastin((r)))
      was aseptically repackaged in 1mL polypropylene syringes, stored at 4 degrees C,
      and analyzed within the preparation day (D0), after 30 days (D30) and 90 days
      (D90). Some syringes were kept for up to 8 months to observe possible
      instability. Several complementary and stability-indicating analytical methods
      were used to assess in details the primary, secondary and tertiary structure of
      the antibody during its conservation: ionic chromatography, size-exclusion
      chromatography, peptide mapping, 2nd derivative UV and IR spectroscopy,
      turbidimetry, diffraction laser spectroscopy, thermal denaturation curves,
      microscopic examination and image analysis. RESULTS: We clearly demonstrate that
      the commercial solution of bevacizumab can be safely repackaged in polypropylene
      syringes and stored up to 3 months at 4 degrees C without alteration of its
      primary, secondary and tertiary structure. The only difference observed is the
      contamination of the syringe content by silicone oil microdroplets, which is
      quite immediate and does not change significantly during the storage in terms of
      number and size. CONCLUSION: Our results support the off-label use of repackaged
      bevacizumab by intravitreal administration, at least from a pharmaceutical point
      of view, with a validated stability of 3 months. This stability period is largely
      enough to practical situations and support current practices, such as in advance
      or batch preparations, which present major advantages in terms of GMP respect,
      workload optimization and financial savings.

PMID- 22655583
TI  - Stability of ready-to-use temsirolimus infusion solution (100mg/L) in
      polypropylene containers under different storage conditions.
AB  - The aim of this study was to determine the stability of ready-to-use temsirolimus
      infusion solutions under different storage conditions. Solutions were prepared in
      polypropylene containers by adding temsirolimus injection to 0.9% sodium chloride
      infusion to reach a final concentration of 100mg/L. The following storage
      conditions were tested: (i) 4(o)C in the refrigerator; (ii) 20(o)C under room
      light exposure and light protection; and (iii) outdoor temperature with sunlight
      exposure. Moreover, stress testing was performed on drug substance at 20(o)C
      under ultraviolet (UV) radiation (365 nm). A stability-indicating high
      performance liquid chromatography (HPLC) method with UV detection was developed
      for this analysis. Precision was below 4% and accuracy ranged from 97 to 102%.
      The lower limit of quantitation was 0.1mg/L. The degradation products produced
      after UV light exposure were detected upon further analysis by mass spectrometry
      detection. The stability of temsirolimus is light and temperature dependent.
      After storage at 20(o)C with room light exposure, the rate of degradation was
      around 0.25%/h; after 1 day, 92.5% of the initial temsirolimus concentration was
      recovered. When protected from light, at 4 and 20(o)C, losses were decelerated;
      the decrease in drug concentration was 1.0 and 1.56% per day, respectively. Under
      daylight exposure, a substantial decrease in drug concentration was observed;
      after 1h, losses were higher than 10%. Exposed to UV light, half of the drug was
      lost after 45 min. In conclusion, temsirolimus 100mg/L in infusion polypropylene
      bags containing 0.9% sodium chloride was chemically stable when protected from
      light for 4 and 3 days at 4 and 20(o)C, respectively.

PMID- 22655584
TI  - [Adult refractory Still disease with atypical articular manifestations:
      efficacity of interleukin-6 antagonists (tocilizumab)].
AB  - INTRODUCTION: Tocilizumab is a humanized monoclonal antibody directed against
      interleukin-6 receptor and is beginning to be reported as effective in some cases
      of Still's disease refractory in adults (ASD). ASD is rare, heterogeneous, with
      unpredictable evolution. The distal destructive arthritis represents a possible
      complication. PATIENT: We report an unusual case of adult-onset Still's disease
      with severe distal interphalangeal destructive arthritis with refractory early
      and prolonged remission after the first tocilizumab infusion. CONCLUSION:
      Tocilizumab can be used in patients with refractory ASD after failure or
      intolerance of conventional treatments.

PMID- 22655585
TI  - Drug-related problems identified by clinical pharmacist's students and
      pharmacist's interventions.
AB  - BACKGROUND: Drug-related problems constitute a major public health problem,
      because of their consequences on morbidity, mortality and cost. PATIENTS AND
      METHODS: A 6-month prospective study was conducted, including hospitalized
      patients in the internal medicine ward of the University Hospital of Beirut, in
      order to identify drug-related problems by clinical pharmacist's students
      participating in routine medical rounds, to assess the characteristics of
      patients presenting these drug-related problems and to analyze pharmacist's
      interventions. RESULTS: Ninety patients presenting drug-related problems were
      identified. Thirty-two percent were hydro-electrolytic problems and 24%
      gastrointestinal. Cardiovascular drugs were the most frequently implicated (44%),
      followed by anticoagulants (17%) and corticosteroids (14%). The most commonly
      identified drug-related problems were drug interactions (37%), overdosage (28%),
      non-conformity to guidelines or contra-indications (23%), underdosage (10%) and
      improper administration (2%). The clinical pharmacist's interventions consisted
      of dose adjustment (38%), addition drugs (31%), changes in drugs (29%) and
      optimization of administration (2%). DISCUSSION AND CONCLUSION: To decrease the
      risk of drug-related problems, drug treatment requires physicians to abide by
      prescribing recommendations, notably in elderly patients, as well as pharmacists'
      effective intervention at all levels. Routine participation of clinical
      pharmacists in clinical medical rounds facilitates the identification of drug
      related problems and may prevent their occurrence.

PMID- 22655589
TI  - Investigation of tryptophan hydroxylase 2 (TPH2) in schizophrenia and in the
      response to antipsychotics.
AB  - Serotonergic transmission is considered relevant in the pathophysiology and the
      treatment of schizophrenia. Tryptophan hydroxylase (TPH) is the rate limiting
      enzyme in the biosynthesis of serotonin. While the TPH1 gene has been found to be
      associated with schizophrenia, studies focusing on TPH2 variants did not yield
      conclusive results for schizophrenia or the response to antipsychotic medication.
      We analyzed eleven TPH2 SNPs in two case-control samples consisting of 4453
      individuals in total. Six SNPs were selected because of their potential
      functional relevance (rs4570625, rs11178997, rs11178998, rs7954758, rs7305115,
      and, rs4290270) and were supported by another 5 tagging SNPs selected based on
      HapMap LD information. In the discovery sample (1476 individuals), we observed a
      significant association with schizophrenia for rs10784941 (p = 0.009, OR minor G
      allele 0.82 [0.71-0.95]) and rs4565946 (p = 0.011, OR minor T-allele 0.83 [0.71
      0.96]). Association was also observed with a common rs4570625-rs4565946 haplotype
      (OR G-C haplotype 1.20 [1.02-1.40]; p = 0.0046). Single-marker associations could
      not be replicated in the replication sample consisting of 2977 individuals, but
      there was a strong trend regarding the rs4570625-rs4565946 G-C haplotype (OR 1.10
      [0.98-1.24]; p(one-sided test) = 0.054). In smaller sub-samples, the rare
      rs4570625-rs4565946 T-T haplotype was associated with reduced processing speed (n
      = 193, p = 0.004) and sensorimotor gating (n = 68, p = 0.006) of schizophrenia
      patients. TPH2 variants and the rs4570625-rs4565946 G-C haplotype did not
      influence the beneficial response to antipsychotic drugs (n = 210) after four
      weeks of treatment administering the Positive and Negative Syndrome Scale of
      Schizophrenia (PANSS). We also investigated the association of the SNPs to
      treatment response, but did not get significant results. In sum, our results
      argue for only a minor role of TPH2 in schizophrenia.

PMID- 22655591
TI  - Letter to the editor: barrow ruptured aneurysm trial.

PMID- 22655590
TI  - Attenuation of limb loss in an experimentally induced hindlimb ischemic model by
      fibroblast growth factor-2/fragmin/protamine microparticles as a delivery system.
AB  - Fibroblast growth factor-2 (FGF-2) is a well-characterized protein that is used
      in the treatment of healing-impaired wounds. We previously reported that
      fragmin/protamine microparticles (F/P MPs) are useful as biodegradable carriers
      for the controlled release of cytokines. We examined the ability of FGF-2
      containing (FGF-2/) F/P MPs to prevent limb loss in an experimentally induced
      ischemic hindlimb model using adult Balb/c-nu/nu male mice. One day after
      inducing ischemia, intramuscular injections of 100 MUL of FGF-2/F/P MPs turbid
      suspension (10 MUg/mL FGF-2 and 6 mg/mL F/P MPs) were administered into eight
      sites of the ischemic hindlimb. A 100-MUL suspension of each of the following-10
      MUg/mL FGF-2, 6 mg/mL F/P MPs, and phosphate-buffered saline (PBS; the control)
      was similarly injected into the hindlimb. From 5 days onward after the
      injections, recovery from ischemia was observed in the FGF-2/F/P MP-treated
      group, but only partial recovery occurred in the FGF-2-treated group. The F/P MP
      treated and PBS-treated groups (i.e., control) exhibited no recovery from the
      ischemia. The histological evaluations of the hindlimbs also confirmed that the
      capillary (i.e., mature vessels) density was significantly higher in the FGF
      2/F/P MP-treated group than in the other groups. The mice injected with FGF-2/F/P
      MPs also recovered hindlimb blood flow, as reflected by oxygen saturation and
      surface temperature evaluation. Our present approach using FGF-2/F/P MPs could be
      considered a valuable option for the therapeutic treatment of peripheral ischemic
      diseases.

PMID- 22655592
TI  - Barrow ruptured aneurysm trial.

PMID- 22655593
TI  - Targeted delivery of nerve growth factor via encapsulated cell biodelivery in
      Alzheimer disease: a technology platform for restorative neurosurgery.
AB  - OBJECT: The authors describe the first clinical trial with encapsulated cell
      biodelivery (ECB) implants that deliver nerve growth factor (NGF) to the
      cholinergic basal forebrain with the intention of halting the degeneration of
      cholinergic neurons and the associated cognitive decline in patients with
      Alzheimer disease (AD). The NsG0202 implant (NsGene A/S) consists of an NGF
      producing, genetically engineered human cell line encapsulated behind a
      semipermeable hollow fiber membrane that allows the influx of nutrients and the
      efflux of NGF. The centimeter-long capsule is attached to an inert polymer tether
      that is used to guide the capsule to the target via stereotactic techniques and
      is anchored to the skull at the bur hole. METHODS: Six patients with mild to
      moderate AD were included in this Phase Ib open-label safety study and were
      divided into 2 dose cohorts. The first cohort of 3 patients received single
      implants targeting the basal nucleus of Meynert (Ch4 region) bilaterally (2
      implants per patient), and after a safety evaluation, a second cohort of 3
      patients received bilateral implants (a total of 4 implants per patient)
      targeting both the Ch4 region and the vertical limb of the diagonal band of Broca
      (Ch2 region). Stereotactic implantation of the devices was successfully
      accomplished in all patients. Despite extensive brain atrophy, all targets could
      be reached without traversing sulci, the insula, or lateral ventricles. RESULTS:
      Postoperative CT scans allowed visualization of the barium-impregnated tethers,
      and fusion of the scans with stereotactic MR images scan was used to verify the
      intended positions of the implants. Follow-up MRI at 3 and 12 months
      postimplantation showed no evidence of inflammation or device displacement. At 12
      months, implants were successfully retrieved, and low but persistent NGF
      secretion was detected in half of the patients. CONCLUSIONS: With refinement, the
      ECB technology is positioned to become an important therapeutic platform in
      restorative neurosurgery and, in combination with other therapeutic factors, may
      be relevant for the treatment of a variety of neurological disorders. Clinical
      trial registration no.: NCT01163825.

PMID- 22655594
TI  - Extent of tumor removal and molecular markers in cerebral glioblastoma: a
      combined prognostic factors study in a surgical series of 105 patients.
AB  - OBJECT: In this paper, the authors' goal was to evaluate the prognostic value of
      YKL-40 expression as a prognostic factor for glioblastomas and to compare its
      validity to the already known MGMT. METHODS: Between January 2002 and January
      2007, 105 patients were treated for cerebral glioblastoma. The extent of removal
      was classified in 4 groups. YKL-40 expression was evaluated by a semiquantitative
      immunohistochemical staining scale (0, no staining; 1, mild expression; and 2,
      strong expression). MGMT promoter methylation status was analyzed with
      methylation-specific polymerase chain reaction. All patients received adjuvant
      radiotherapy and chemotherapy. Kaplan-Meier curves were used to analyze
      progression-free survival (PFS) and overall survival (OS), and to compare these
      parameters between the subgroups stratified by extent of surgical removal, MGMT
      methylation, and YKL-40 expression. The log-rank test was used to determine
      statistical significance. A multivariate regression analysis was applied to
      extent of removal, YKL-40 expression, and MGMT status to check their specific
      statistical power and to test the independence of the variables. RESULTS: There
      were 55 men and 50 women with a mean age of 58 years. Extent of surgical removal
      is reported. The MGMT promoter was methylated in 48 patients and nonmethylated in
      57. Analysis of YKL-40 expression is reported. The median PFS was 10.7 months
      (14.9 months in the gross-total removal subgroup) (p < 0.0001), and the median OS
      was 12.5 months (17.4 months in the gross-total removal group) (p < 0.0001). In
      the univariate analysis, OS was significantly correlated to the extent of
      resection (p < 0.0001), MGMT status (p < 0.0001), and YKL-40 (p < 0.0001).
      Multivariate analysis showed that all 3 factors reached statistical significance
      with respect to patient survival. In particular, surgical removal contributed
      more than the 2 other factors to the survival prediction (beta = -0.6254).
      Interestingly, YKL-40 (beta = -0.3867) contributed more than MGMT (beta = 
      0.1705) to the predicted survival. CONCLUSIONS: The extent of removal is the most
      important factor influencing the OS of patients harboring glioblastomas. When
      biological aggressiveness is taken into account, YKL-40 expression was found to
      be an independent prognostic factor that predicts OS better than MGMT status.

PMID- 22655595
TI  - Tuning the "roadblock" effect in kinesin-based transport.
AB  - Major efforts are underway to harness motor proteins for technical applications.
      Yet how to best attach cargo to microtubules that serve as kinesin-driven
      "molecular shuttles" without compromising transport performance remains
      challenging. Furthermore, microtubule-associated proteins (MAPs) can block motor
      protein-powered transport in neurons, which can lead to neurodegenerative
      diseases. Again it is unclear how different physical roadblock parameters
      interfere with the stepping motion of kinesins. Here, we employ a series of MAPs,
      tailored (strept)avidins, and DNA as model roadblocks and determine how their
      geometrical, nanomechanical, and electrochemical properties can reduce kinesin
      mediated transport. Our results provide insights into kinesin transport
      regulation and might facilitate the choice of appropriate cargo linkers for motor
      protein-driven transport devices.

PMID- 22655596
TI  - Re: The radiology report - are we getting the message across?

PMID- 22655598
TI  - Advanced technologies for gastrointestinal endoscopy.
AB  - The gastrointestinal tract is home to some of the most deadly human diseases.
      Exacerbating the problem is the difficulty of accessing it for diagnosis or
      intervention and the concomitant patient discomfort. Flexible endoscopy has
      established itself as the method of choice and its diagnostic accuracy is high,
      but there remain technical limitations in modern scopes, and the procedure is
      poorly tolerated by patients, leading to low rates of compliance with screening
      guidelines. Although advancement in clinical endoscope design has been slow in
      recent years, a critical mass of enabling technologies is now paving the way for
      the next generation of gastrointestinal endoscopes. This review describes current
      endoscopes and provides an overview of innovative flexible scopes and wireless
      capsules that can enable painless endoscopy and/or enhanced diagnostic and
      therapeutic capabilities. We provide a perspective on the potential of these new
      technologies to address the limitations of current endoscopes in mass cancer
      screening and other contexts and thus to save many lives.

PMID- 22655601
TI  - Anaerobic degradation.

PMID- 22655602
TI  - Pesticides and plants.

PMID- 22655603
TI  - TCE degradation.

PMID- 22655600
TI  - Quantitative imaging methods for the development and validation of brain
      biomechanics models.
AB  - Rapid deformation of brain tissue in response to head impact or acceleration can
      lead to numerous pathological changes, both immediate and delayed. Modeling and
      simulation hold promise for illuminating the mechanisms of traumatic brain injury
      (TBI) and for developing preventive devices and strategies. However, mathematical
      models have predictive value only if they satisfy two conditions. First, they
      must capture the biomechanics of the brain as both a material and a structure,
      including the mechanics of brain tissue and its interactions with the skull.
      Second, they must be validated by direct comparison with experimental data.
      Emerging imaging technologies and recent imaging studies provide important data
      for these purposes. This review describes these techniques and data, with an
      emphasis on magnetic resonance imaging approaches. In combination, these imaging
      tools promise to extend our understanding of brain biomechanics and improve our
      ability to study TBI in silico.

PMID- 22655599
TI  - Mechanical regulation of nuclear structure and function.
AB  - Mechanical loading induces both nuclear distortion and alterations in gene
      expression in a variety of cell types. Mechanotransduction is the process by
      which extracellular mechanical forces can activate a number of well-studied
      cytoplasmic signaling cascades. Inevitably, such signals are transduced to the
      nucleus and induce transcription factor-mediated changes in gene expression.
      However, gene expression also can be regulated through alterations in nuclear
      architecture, providing direct control of genome function. One putative
      transduction mechanism for this phenomenon involves alterations in nuclear
      architecture that result from the mechanical perturbation of the cell. This
      perturbation is associated with direct mechanical strain or osmotic stress, which
      is transferred to the nucleus. This review describes the current state of
      knowledge relating the nuclear architecture and the transfer of mechanical forces
      to the nucleus mediated by the cytoskeleton, the nucleoskeleton, and the LINC
      (linker of the nucleoskeleton and cytoskeleton) complex. Moreover, remodeling of
      the nucleus induces alterations in nuclear stiffness, which may be associated
      with cell differentiation. These phenomena are discussed in relation to the
      potential influence of nuclear architecture-mediated mechanoregulation of
      transcription and cell fate.

PMID- 22655605
TI  - Plastic films.

PMID- 22655604
TI  - Long-term PCB data from air filters.

PMID- 22655606
TI  - Real biomagnification?

PMID- 22655607
TI  - Supercritical fluid extraction.

PMID- 22655608
TI  - Environment symposium.

PMID- 22655609
TI  - Groundwater tracer.

PMID- 22655610
TI  - Screening model.

PMID- 22655612
TI  - Noncancer risks.

PMID- 22655611
TI  - Negative ion MS.

PMID- 22655614
TI  - Cyanide mobility.

PMID- 22655613
TI  - Two-dimensional GC.

PMID- 22655615
TI  - Soil horizon thickness.

PMID- 22655617
TI  - Constructed reed beds.

PMID- 22655616
TI  - Tidal marsh construction.

PMID- 22655618
TI  - Ozone standard lawsuit.

PMID- 22655619
TI  - Continuous monitoring.

PMID- 22655621
TI  - New analytical laboratory?

PMID- 22655620
TI  - Short-term S02 standards.

PMID- 22655622
TI  - MDL Information Systems, Inc.

PMID- 22655623
TI  - Inhalation studies.

PMID- 22655624
TI  - CFC-free method proposed.

PMID- 22655626
TI  - ES&T Information Express.

PMID- 22655627
TI  - "Reinvention" of EPA research office takes shape.

PMID- 22655625
TI  - Standardized SEPs.

PMID- 22655628
TI  - EPA considering quick action on Cryptosporidium.

PMID- 22655630
TI  - Plant enzymes set for bioremediation field study.

PMID- 22655629
TI  - Mercury increases DNA damage from radiation.

PMID- 22655632
TI  - White House creating "national environmental technology strategy".

PMID- 22655631
TI  - Economic impact of green technologies questioned.

PMID- 22655634
TI  - Final drinking water monitoring rule set for June.

PMID- 22655633
TI  - Turner designs.

PMID- 22655635
TI  - NRC to look at incinerators, human health.

PMID- 22655637
TI  - Impasse reached on European carbon tax.

PMID- 22655636
TI  - EPA regional offices plan multimedia reorganization.

PMID- 22655638
TI  - Stronger voice for environmental justice advocates?

PMID- 22655640
TI  - Big growth predicted for environmental exports to Mexico.

PMID- 22655639
TI  - EPA strategy promises "fundamental reform".

PMID- 22655641
TI  - NuEpsilonRhoAlpha Under Review by CEQ.

PMID- 22655643
TI  - EPA's Dioxin Reassessment.

PMID- 22655642
TI  - Dioxin risk: are we sure yet?

PMID- 22655644
TI  - EPA on the right track.

PMID- 22655646
TI  - EPA assessment not justified.

PMID- 22655648
TI  - What happened to pulp and paper?

PMID- 22655647
TI  - Incinerators targeted by EPA.

PMID- 22655650
TI  - Oxygenates on trial.

PMID- 22655649
TI  - A new formula for fighting urban zone.

PMID- 22655651
TI  - Baseline research on fuels and emissions.

PMID- 22655652
TI  - Reducing ozone: Modeling studies.

PMID- 22655653
TI  - Are PCBs in the Great Lakes Approaching a "New Equilibrium"?

PMID- 22655656
TI  - Analytical products.

PMID- 22655654
TI  - Winners and losers.

PMID- 22655658
TI  - Editorial policy.

PMID- 22655657
TI  - 1995 advisory board.

PMID- 22655659
TI  - Peer review.

PMID- 22655660
TI  - Current Research Author's Guide.

PMID- 22655661
TI  - Classified sectauiotaomicronn.

PMID- 22655662
TI  - Professional services directory.

PMID- 22655663
TI  - Make learning fun with ElementO!

PMID- 22655664
TI  - Index to the advertisers in this issue.

PMID- 22655665
TI  - Stanton miller and change.

PMID- 22655666
TI  - Volcanic CFCs.

PMID- 22655667
TI  - Isidorov's response.

PMID- 22655668
TI  - Author's response.

PMID- 22655669
TI  - Zero emissions?

PMID- 22655670
TI  - Battelle.

PMID- 22655671
TI  - Organometallics.

PMID- 22655672
TI  - Intra-organizational dynamics as drivers of entrepreneurship among physicians and
      managers in hospitals of western countries.
AB  - During the past decade, entrepreneurship in the healthcare sector has become
      increasingly important. The aging society, the continuous stream of innovative
      technologies and the growth of chronic illnesses are jeopardizing the
      sustainability of healthcare systems. In response, many European governments
      started to reform healthcare during the 1990s, replacing the traditional logic of
      medical professionalism with business-like logics. This trend is expected to
      continue as many governments will have to reduce their healthcare spending in
      response to the current growing budget deficits. In the process, entrepreneurship
      is being stimulated, yet little is known about intra-hospital dynamics leading to
      entrepreneurial behavior. The purpose of this article is to review existing
      literature concerning the influence of intra-organizational dynamics on
      entrepreneurship among physicians and managers in hospitals of Western countries.
      Therefore, we conducted a theory-led, systematic review of how intra
      organizational dynamics among hospital managers and physicians can influence
      entrepreneurship. We designed our review using the neo-institutional framework of
      Greenwood and Hinings (1996). We analyze these dynamics in terms of power
      dependencies, interest dissatisfaction and value commitments. Our search revealed
      that physicians' dependence on hospital management has increased along with
      healthcare reforms and the resulting emphasis on business logics. This has
      induced various types of responses by physicians. Physicians can be pushed to
      adopt an entrepreneurial attitude as part of a defensive value commitment toward
      the business-like healthcare logic, to defend their traditionally dominant
      position and professional autonomy. In contrast, physicians holding a
      transformative attitude toward traditional medical professionalism seem more
      prone to adopt the entrepreneurial elements of business-like healthcare,
      encouraged by the prospect of increased autonomy and income. Interest
      dissatisfaction and competing value commitments can also stimulate physicians'
      entrepreneurship and, depending on their relative importance, determine whether
      it is necessity-based or opportunity-driven.

PMID- 22655673
TI  - Gender differences on the impacts of social exclusion on mortality among older
      Japanese: AGES cohort study.
AB  - To evaluate the gender-specific impact of social exclusion on the mortality of
      older Japanese adults, we performed a prospective data analysis using the data of
      the Aichi Gerontological Evaluation Study (AGES). In AGES, we surveyed
      functionally independent residents aged 65 years or older who lived in six
      municipalities in Aichi prefecture, Japan. We gathered baseline information from
      13,310 respondents in 2003. Information on mortality was obtained from municipal
      databases of the public long-term care insurance system. All participants were
      followed for up to 4 years. We evaluated social exclusion in terms of the
      combination of social isolation, social inactivity, and relative poverty. Cox's
      proportional hazard model revealed that socially excluded older people were at
      significantly increased risk (9-34%) for premature mortality. Those with
      simultaneously relative poverty and social isolation and/or social inactivity
      were 1.29 times more likely to die prematurely than those who were not socially
      excluded. Women showed stronger overall impact of social exclusion on mortality,
      whereas relative poverty was significantly associated with mortality risks for
      men. If these associations are truly causal, social exclusion is attributable to
      9000-44,000 premature deaths (1-5%) annually for the older Japanese population.
      Health and social policies to mitigate the issue of social exclusion among older
      adults may require gender-specific approaches.

PMID- 22655674
TI  - 'Relax and take a deep breath': print media coverage of asthma and air pollution
      in the United States.
AB  - The media are an important social actor in the construction of the public's
      understanding of the complex relationships between the environment and their
      health. This paper explores the print media's coverage of the relationship
      between asthma and air pollution, focusing on the portrayal of causal certainty
      between exposure to various forms of air pollution and the etiology and
      exacerbation of the disease. By examining twenty years of newspaper articles from
      the New York Times Los Angeles Times, and the Washington Post, this paper
      presents findings on trends across time, within papers, and across key themes.
      Although the print media's coverage of asthma and its environmental correlates
      has increased over time, this paper finds relatively little coherence in whether
      asthma is portrayed as directly caused by air pollution or triggered by
      exposures. In terms of coverage, outdoor sources of air pollution are covered
      more frequently - but with less certainty in the discussion of specific
      relationships. This lack of coherence and specificity in the portrayal of asthma
      as an environmental disease may weaken regulators' ability to act in passing air
      pollution reforms by lowering the public's interest and concern.

PMID- 22655675
TI  - The rights of psychiatric patients in China: a survey of medical staff and
      consumers' attitudes toward patient participation in clinical trials.
AB  - To explore and compare attitudes of consumers (patients and their family members)
      and medical staff toward clinical trials related to mental health in China, we
      developed two questionnaires for medical staff and patients and their family
      members. Approximately 66.2% of medical staff who had no research experience
      believed that patients could be persuaded to participate in clinical trials, but
      the percentage of consumers who believed so was just 12.5%. Both groups agreed
      that written informed consent was required; however, more medical staff than
      patients agreed that such consent could be provided by patients or their guardian
      (88.4% vs. 71.4%). Only 9.5% of medical staff thought that patient treatment
      would be compromised by refusal to participate; the proportion of consumers who
      thought the same was 29.4%. Great differences exist between medical staff and
      consumers' attitudes and beliefs regarding clinical trials. Medical staff were
      more likely to have a favorable attitude toward their patients participating in
      clinical trials and considered that informed consent could be provided by
      guardians rather than the patient.

PMID- 22655676
TI  - The emergence of factor Xa inhibitors for the treatment of cardiovascular
      diseases: a patent review.
AB  - INTRODUCTION: Factor Xa (FXa) is a critical enzyme in the coagulation cascade
      responsible for thrombin generation, the final enzyme that leads to fibrin clot
      formation. Significant success has recently been reported with compounds such as
      rivaroxaban, apixaban and edoxaban in the treatment and prevention of venous
      thromboembolism (VTE) and more recently in the prevention of stroke in atrial
      fibrillation (AF). The success these agents have demonstrated is now being
      reflected by a narrowing of new FXa patents over the past few years. The new
      patents appear to be structural modifications of previously published, small
      molecule inhibitors and bind in a similar manner to the FXa enzyme. AREAS
      COVERED: SciFinder(r), PubMed and Google websites were used as the main source of
      literature retrieval. Patent searches were conducted in the patent databases:
      HCAPlus, WPIX and the full text databases (USPAT2, USPATFULL, EPFULL, PCTFULL)
      using the following keywords: ((FXa) OR (F OR factor) (W) (Xa)) (S) (inhibit? or
      block? or modulat? or antagonist? or regulat?). The search was restricted to
      patent documents with the entry date on or after 1 January 2009. Literature and
      information related to clinical development was retrieved from Thomson Reuter's
      Pharma. EXPERT OPINION: A large body of Phase II and Phase III data is now
      available for FXa inhibitors such as rivaroxaban, apixaban, edoxaban and
      betrixaban. The clinical data demonstrate favorable benefit-risk profiles
      compared with the standards of care for short- and long-term anticoagulation
      (i.e., low molecular weight heparins (LMWHs) and wafarin). The potential exists
      that these agents will eventually be the agents of choice for the treatment of a
      host of cardiovascular disease states, offering improved efficacy, safety, and
      ease of use compared with existing anticoagulants.

PMID- 22655679
TI  - Emerging inorganic nanomaterials for pancreatic cancer diagnosis and treatment.
AB  - Pancreatic cancer is a devastating disease with incidence increasing at an
      alarming rate and survival not improved substantially during the past three
      decades. Although enormous efforts have been made in early detection and
      comprehensive treatment for this disease, little or no survival improvement was
      obtained, which necessitates the development of novel strategies. Emerging
      inorganic nanomaterials, such as carbon nanotubes, quantum dots, mesoporous
      silica/gold/supermagnetic nanoparticles, have been widely used in biomedical
      research with great optimism for cancer diagnosis and therapy. Such nanoparticles
      possess unique optical, electrical, magnetic and/or electrochemical properties.
      With such properties along with their impressive nano-size, these particles can
      be targeted to cancer cells, tissues, and ligands efficiently and monitored with
      extreme precision in real-time. In additional to liposome, dendrimer, and
      polymeric nanoparticles, they are considered the most promising nanomaterials
      with the capability of both cancer detection and multimodality treatment.
      Emerging approaches to harness nanotechnology to optimize the existing diagnostic
      and therapeutic tools for pancreatic cancer have been extensively explored during
      the recent years. Future options for early detection, individual therapy and
      monitoring responses of pancreatic cancer are focused on multifunctional
      nanomedicine. In this review, we present the recent development of clinically
      applicable inorganic nanoparticles, with focus on the diagnosis and treatment of
      pancreatic cancer. Furthermore, their advantages in theranostic nanomedicine, and
      challenges of translation to clinical practice, are discussed.

PMID- 22655677
TI  - Hidden genetic diversity in the green alga Spirogyra (Zygnematophyceae,
      Streptophyta).
AB  - BACKGROUND: The unbranched filamentous green alga Spirogyra (Streptophyta,
      Zygnemataceae) is easily recognizable based on its vegetative morphology, which
      shows one to several spiral chloroplasts. This simple structure falsely points to
      a low genetic diversity: Spirogyra is commonly excluded from phylogenetic
      analyses because the genus is known as a long-branch taxon caused by a high
      evolutionary rate. RESULTS: We focused on this genetic diversity and sequenced
      130 Spirogyra small subunit nuclear ribosomal DNA (SSU rDNA) strands of different
      origin. The resulting SSU rDNA sequences were used for phylogenetic analyses
      using complex evolutionary models (posterior probability, maximum likelihood,
      neighbor joining, and maximum parsimony methods). The sequences were between 1672
      and 1779 nucleotides long. Sequence comparisons revealed 53 individual clones,
      but our results still support monophyly of the genus. Our data set did not
      contain a single slow-evolving taxon that would have been placed on a shorter
      branch compared to the remaining sequences. Out of 130 accessions analyzed, 72
      showed a secondary loss of the 1506 group I intron, which formed a long-branched
      group within the genus. The phylogenetic relationship to the genus Spirotaenia
      was not resolved satisfactorily. The genetic distance within the genus Spirogyra
      exceeded the distances measured within any other genus of the remaining
      Zygnemataceae included in this study. CONCLUSION: Overall, we define eight
      distinct clades of Spirogyra, one of them including the genus Sirogonium. A large
      number of non-homoplasious synapomorphies (NHS; 114 NHS in total) was found for
      Spirogyra (41 NHS) and for each clade (totaling 73 NHS). This emphasizes the high
      genetic diversity of this genus and the distance to the remaining
      Zygnematophyceae.

PMID- 22655680
TI  - [Introduction to this issue].

PMID- 22655678
TI  - Clear cell carcinoma of the ovary: is there a role of histology-specific
      treatment?
AB  - Several clinical trials to establish standard treatment modality for ovarian
      cancers included a high abundance of patients with serous histologic tumors,
      which were quite sensitive to platinum-based chemotherapy. On the other hand,
      ovarian tumor with rare histologic subtypes such as clear cell or mucinous tumors
      have been recognized to show chemo-resistant phenotype, leading to poorer
      prognosis. Especially, clear cell carcinoma of the ovary (CCC) is a distinctive
      tumor, deriving from endometriosis or clear cell adenofibroma, and response rate
      to platinum-based therapy is extremely low. It was implied that complete surgical
      staging enabled us to distinguish a high risk group of recurrence in CCC patients
      whose disease was confined to the ovary (pT1M0); however, complete surgical
      staging procedures could not lead to improved survival. Moreover, the status of
      peritoneal cytology was recognized as an independent prognostic factor in early
      staged CCC patients, even after complete surgical staging. In advanced cases with
      CCC, the patients with no residual tumor had significantly better survival than
      those with the tumor less than 1 cm or those with tumor diameter more than 1 cm.
      Therefore, the importance of achieving no macroscopic residual disease at primary
      surgery is so important compared with other histologic subtypes. On the other
      hand, many studies have shown that conventional platinum-based chemotherapy
      regimens yielded a poorer prognosis in patients with CCC than in patients with
      serous subtypes. The response rate by paclitaxel plus carboplatin (TC) was
      slightly higher, ranging from 22% to 56%, which was not satisfactory enough.
      Another regimen for CCC tumors is now being explored: irinotecan plus cisplatin,
      and molecular targeting agents. In this review article, we discuss the surgical
      issues for early-staged and advanced CCC including possibility of fertility
      sparing surgery, and the chemotherapy for CCC disease.

PMID- 22655681
TI  - [Retrospective study of the distribution and the fertility of hydatid cysts in
      the child in Tunisia].
AB  - PURPOSE OF THE STUDY: Our aim was to study the distribution and the fertility of
      the hydatid cysts in function of the age and the sex of patients and to identify
      the strain(s) responsible(s) of the children hydatidosis. PATIENTS AND METHODS:
      We have analyzed a total of 241 cysts coming from 195 children aged 2 to 16 years
      operated in the CHU F. Bourguiba of Monastir during the period from November 1999
      to December 2009. For each cyst, the localization and the fertility of the
      metacestode as well as age, sex and origin of the patient are listed.
      Identification of strains was carried out by PCR/RFLP and has targeted the
      ribosomal gene ITS1. RESULTS: The lung was the primary localization of cyst
      (61.8%) followed by the liver (34.85%). The greatest number of cases is observed
      in the age groups 4-9 years (138 cases) where children's infection is more
      frequent in the male than in the female sex. The fertility of the cyst was
      independent of its site or its size and no incidence of age of children was
      detected. The G1 sheep strain is responsible for the contamination of children.
      CONCLUSION: The cystic echinococcosis described as a young adult disease may
      actually observed at any age and remains a serious problem of public health in
      Tunisia.

PMID- 22655682
TI  - From invasion to extinction in heterogeneous neural fields.
AB  - In this paper, we analyze the invasion and extinction of activity in
      heterogeneous neural fields. We first consider the effects of spatial
      heterogeneities on the propagation of an invasive activity front. In contrast to
      previous studies of front propagation in neural media, we assume that the front
      propagates into an unstable rather than a metastable zero-activity state. For
      sufficiently localized initial conditions, the asymptotic velocity of the
      resulting pulled front is given by the linear spreading velocity, which is
      determined by linearizing about the unstable state within the leading edge of the
      front. One of the characteristic features of these so-called pulled fronts is
      their sensitivity to perturbations inside the leading edge. This means that
      standard perturbation methods for studying the effects of spatial heterogeneities
      or external noise fluctuations break down. We show how to extend a partial
      differential equation method for analyzing pulled fronts in slowly modulated
      environments to the case of neural fields with slowly modulated synaptic weights.
      The basic idea is to rescale space and time so that the front becomes a sharp
      interface whose location can be determined by solving a corresponding local
      Hamilton-Jacobi equation. We use steepest descents to derive the Hamilton-Jacobi
      equation from the original nonlocal neural field equation. In the case of weak
      synaptic heterogenities, we then use perturbation theory to solve the
      corresponding Hamilton equations and thus determine the time-dependent wave
      speed. In the second part of the paper, we investigate how time-dependent
      heterogenities in the form of extrinsic multiplicative noise can induce rare
      noise-driven transitions to the zero-activity state, which now acts as an
      absorbing state signaling the extinction of all activity. In this case, the most
      probable path to extinction can be obtained by solving the classical equations of
      motion that dominate a path integral representation of the stochastic neural
      field in the weak noise limit. These equations take the form of nonlocal Hamilton
      equations in an infinite-dimensional phase space.

PMID- 22655683
TI  - Combination of temperature-sensitive stem cells and mild hypothermia: a new
      potential therapy for severe traumatic brain injury.
AB  - Stem cell transplantation holds great potential for the treatment of traumatic
      brain injury (TBI). However, the micro-environment of reduced oxygen and
      accumulated toxins leads to low survival rates of grafted cells, which
      dramatically limits their clinical application. Mild hypothermia has been
      demonstrated to improve the micro-environment after severe TBI. Thus, we
      speculate that combinational therapy of mild hypothermia may promote survival of
      grafted cells, especially temperature-sensitive stem cells, which show the most
      activity in mild temperatures. In this study, we first isolated mesenchymal stem
      cells from umbilical cord (UCSMCs) and generated the temperature-sensitive UCSMCs
      (tsUCSMCs) by infection with a retrovirus carrying the temperature-sensitive
      tsA58 SV40 LT antigen gene. We demonstrated that tsUCSMCs grew and proliferated
      with more activity at 33 degrees C than at 37 degrees C by counting cell numbers
      with a hematocytometer, measuring the cell cycle with flow cytometry, and
      detecting proliferating cell nuclear antigen (PCNA) with immunofluorescence
      staining. Thereafter, we established the rat severe TBI model by fluid
      percussion, and injected PBS, UCSMCs, or tsUCSMCs into the injured region, and
      subject the animals to normothermia or mild hypothermia (33 degrees C). We found
      that, compared with UCSMC or tsUCSMC treatment alone, their combination with
      hypothermia could significantly improve motor and cognitive function with more
      survival of the grafted cells. Furthermore, we observed that combined therapy
      with hypothermia and tsUCSMCs exerted the most protective effect on the recovery
      of neurological function of all the tested treatments, with the highest survival
      and proliferation rates, and the lowest apoptosis rate. Thus this may represent a
      new therapeutic strategy for the treatment of severe TBI.

PMID- 22655687
TI  - Cotransplantation of adipose-derived mesenchymal stromal cells and endothelial
      cells in a modular construct drives vascularization in SCID/bg mice.
AB  - A modular approach to adipose tissue engineering was explored by embedding
      adipose-derived mesenchymal stromal cells (adMSC) in sub-mm-sized collagen rods
      or "modules" and coating with human microvascular endothelial cells (HMEC). After
      subcutaneous injection into a SCID/Bg mouse, HMEC on modules containing embedded
      adMSC appeared to detach from the modules to form vessels as early as day 3, as
      confirmed by the human EC-specific UEA-1 lectin stain, and these vessels
      persisted for up to 90 days. Vessel numbers decreased over 14 days, but vessel
      size increased suggesting a maturing of the vasculature. Vessel perfusion with
      the host was confirmed at 21 days by microCT. HMEC on modules without embedded
      adMSC remained attached to the module surface at day 3 and UEA-1 staining
      disappeared over 14 days suggesting cell death. It appeared that
      cotransplantation with adMSC had an anti-apoptotic and proangiogenic effect on
      HMEC. The early revascularization strategy may be successful in supporting adMSC
      viability and differentiation, as a preliminary study suggests progressive fat
      accumulation in the HMEC+adMSC implants: ~60% of the implant area stained
      positive for Oil Red O by day 90. adMSC-embedded modules without HMEC surface
      coating did not show similar levels of Oil Red O staining. All implant volumes
      decreased over the time course of the experiment, yet HMEC+adMSC module implants
      were larger than adMSC-only implants at day 90. Collagen gel is mechanically weak
      and contracts in vivo making it unsuitable as a biomaterial for adipose tissue
      engineering where volume maintenance is critical. When combined with an
      appropriate biomaterial, the modular approach to adipose tissue engineering may
      represent a successful strategy to engineer soft tissue substitutes of clinical
      relevance.

PMID- 22655690
TI  - Cerebrospinal fluid fistula prevention and treatment following frontal sinus
      fractures: a review of initial management and outcomes.
AB  - Frontal sinus fractures are heterogeneous, and management of these fractures is
      often modified based on injury pattern and institutional experience. The optimal
      initial treatment of frontal sinus fractures is controversial. Treatment
      strategies are aimed at correcting cosmetic deformity, as well as at preventing
      delayed complications, including CSF fistulas, mucocele formation, and infection.
      Existing treatment options include observation, reconstruction, obliteration,
      cranialization, or a combination thereof. Modalities for treatment encompass both
      open surgical approaches and endoscopic techniques. In the absence of Class I
      data, the authors review the existing literature related to treatment strategies
      of frontal sinus fractures, particularly as they relate to CSF fistulas, to
      provide recommendations based on the best available evidence.

PMID- 22655691
TI  - Spontaneous and medically induced cerebrospinal fluid leakage in the setting of
      pituitary adenomas: review of the literature.
AB  - OBJECT: Spontaneous and medically induced CSF leaks are uncommonly associated
      with pituitary adenomas. The aim of this study was to further characterize the
      clinical scenarios most closely associated with this phenomenon. METHODS: A
      review of the literature was conducted to identify all cases of nonsurgical CSF
      leaks associated with pituitary adenomas. The authors aimed to identify
      associated risk factors and management strategies used to treat these tumors and
      repair the CSF leak site. RESULTS: Fifty-two patients with spontaneous or
      medically induced CSF leaks in the setting of a pituitary adenoma were identified
      from 29 articles published from 1980 through 2011. In 38 patients (73%), CSF
      rhinorrhea developed following initiation of medical therapy, whereas spontaneous
      CSF leakage developed as the presenting symptom in 14 patients (27%). The
      patients' mean age was 42.8 years (range 23-68 years). There were 35 males and 17
      females. Forty-two patients (81%) had a prolactinoma, with the remaining patients
      having the following tumors: nonfunctioning pituitary adenoma (6 patients),
      growth hormone-secreting adenoma (2 patients), mammosomatotroph cell adenoma (1
      patient), and ACTH-secreting adenoma (1 patient). Infrasellar tumor invasion into
      the paranasal sinuses was specifically reported in 56% of patients. The medical
      agents associated with CSF leakage were dopamine agonists (97%) and somatostatin
      analogs (3%). The average time from initialization of medical treatment to onset
      of rhinorrhea was 3.3 months (range 3 days-17 months). Nonsurgical management was
      successful in 4 patients, including 1 who had successful resolution with a
      temporary lumbar drain. Forty-six patients (88%) underwent surgical intervention
      to treat the CSF leak and/or resect the tumor. In 2 patients, surgery was not
      performed due to medical contraindications or patient preference. CONCLUSIONS:
      Nonsurgical development of CSF rhinorrhea may occur in the setting of pituitary
      adenomas, especially following favorable response of invasive prolactinomas to
      initiation of dopamine agonist therapy. Additional cases have been reported as
      the presenting symptom of a pituitary adenoma and are likely to be related to
      decreased tumor volume due to intrinsic infarction or hemorrhage, ongoing
      invasion, and/or increases in intracranial pressure. Surgical repair,
      preferentially via a transsphenoidal approach, is the recommended initial
      treatment for definitive repair of the CSF leak and achievement of maximal tumor
      resection.

PMID- 22655692
TI  - Diagnosis and treatment of cerebrospinal fluid rhinorrhea following accidental
      traumatic anterior skull base fractures.
AB  - Cerebrospinal fluid rhinorrhea is a serious and potentially fatal condition
      because of an increased risk of meningitis and brain abscess. Approximately 80%
      of all cases occur in patients with head injuries and craniofacial fractures.
      Despite technical advances in the diagnosis and management of CSF rhinorrhea
      caused by craniofacial injury through the introduction of MRI and endoscopic
      extracranial surgical approaches, difficulties remain. The authors review here
      the pathophysiology, diagnosis, and management of CSF rhinorrhea relevant
      exclusively to traumatic anterior skull base injuries and attempt to identify
      areas in which further work is needed.

PMID- 22655688
TI  - Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding
      proteins, PTBP1 and PTBP2.
AB  - Alternative splicing patterns are regulated by RNA binding proteins that assemble
      onto each pre-mRNA to form a complex RNP structure. The polypyrimidine tract
      binding protein, PTB, has served as an informative model for understanding how
      RNA binding proteins affect spliceosome assembly and how changes in the
      expression of these proteins can control complex programs of splicing in tissues.
      In this review, we describe the mechanisms of splicing regulation by PTB and its
      function, along with its paralog PTBP2, in neuronal development.

PMID- 22655693
TI  - Is posttraumatic cerebrospinal fluid fistula a predictor of posttraumatic
      meningitis? A US Nationwide Inpatient Sample database study.
AB  - OBJECT: Various factors have been reported in literature to be associated with
      the development of posttraumatic meningitis. There is a paucity of data regarding
      skull fractures and facial fractures leading to CSF leaks and their association
      with the development of meningitis. The primary objective of this study was to
      analyze the US Nationwide Inpatient Sample (NIS) database to elucidate the
      factors associated with the development of posttraumatic meningitis. A secondary
      goal was to analyze the overall hospitalization cost related to posttraumatic
      meningitis and factors associated with that cost. METHODS: The NIS database was
      analyzed to identify patients admitted to hospitals with a diagnosis of head
      injury from 2005 through 2009. This data set was analyzed to assess the
      relationship of various clinical parameters that may affect the development of
      posttraumatic meningitis using binary logistic regression models. Additionally,
      the overall hospitalization cost for the head injury patients who did not undergo
      any neurosurgical intervention was further categorized into quartile groups, and
      a regression model was created to analyze various factors responsible for
      escalating the overall cost of the hospital stay. RESULTS: A total of 382,267
      inpatient admissions for head injury were analyzed for the 2005-2009 period.
      Meningitis was reported in 0.2% of these cases (708 cases). Closed skull base
      fractures, open skull base fractures, cranial vault fractures, and maxillofacial
      fractures were reported in 20,524 (5.4%), 1089 (0.3%), 5064 (1.3%), and 88,649
      (23.2%) patients, respectively. Among these patients with fractures, meningitis
      was noted in 0.17%, 0.18%, 0.05%, and 0.10% admissions, respectively.
      Cerebrospinal fluid rhinorrhea was reported in 453 head injury patients (0.1%)
      and CSF otorrhea in 582 (0.2%). Of the patients reported to have CSF rhinorrhea,
      35 (7.7%) developed meningitis, whereas in the cohort with CSF otorrhea, 15
      patients (2.6%) developed meningitis. Cerebrospinal fluid rhinorrhea (p < 0.001,
      OR 22.8, 95% CI 15.6-33.3), CSF otorrhea (p < 0.001, OR 9.2, 95% CI 5.2-16.09),
      and major neurosurgical procedures (p < 0.001, OR 5.6, 95% CI 4.8-6.5) were
      independent predictors of meningitis. Further, CSF rhinorrhea (p < 0.001, OR 2.0,
      95% CI 1.6-2.7), CSF otorrhea (p < 0.001, OR 2.3, 95% CI 1.9-2.7), and
      posttraumatic meningitis (p < 0.001, OR 3.1, 95% CI 2.5-3.8) were independent
      factors responsible for escalating the cost of head injury in cases not requiring
      any major neurosurgical intervention. CONCLUSIONS: Cerebrospinal fluid rhinorrhea
      and CSF otorrhea are independent predictors of posttraumatic meningitis.
      Furthermore, meningitis and CSF fistulas may independently lead to significantly
      increased cost of hospitalization in head injury patients not undergoing any
      major neurosurgical intervention.

PMID- 22655694
TI  - Surgical nuances for the endoscopic endonasal transpterygoid approach to lateral
      sphenoid sinus encephaloceles.
AB  - Lateral sphenoid encephaloceles of the Sternberg canal are rare entities and
      usually present with spontaneous CSF rhinorrhea. Traditionally, these were
      treated via transcranial approaches, which can be challenging given the deep
      location of these lesions. However, with advancements in endoscopic skull base
      surgery, including improved surgical exposures, angled endoscopes and
      instruments, and novel repair techniques, these encephaloceles can be resected
      and successfully repaired with purely endoscopic endonasal approaches. In this
      report, the authors review the endoscopic endonasal transpterygoid approach to
      the lateral recess of the sphenoid sinus for repair of temporal lobe
      encephaloceles, including an overview of the surgical anatomy from an endoscopic
      perspective, and describe the technical operative nuances and surgical pearls for
      these cases. The authors also present 4 new cases of lateral sphenoid recess
      encephaloceles that were successfully treated using this approach.

PMID- 22655696
TI  - Surgical nuances for nasoseptal flap reconstruction of cranial base defects with
      high-flow cerebrospinal fluid leaks after endoscopic skull base surgery.
AB  - Extended endoscopic endonasal approaches have allowed for a minimally invasive
      solution for removal of a variety of ventral skull base lesions, including
      intradural tumors. Depending on the location of the pathological entity, various
      types of surgical corridors are used, such as transcribriform, transplanum
      transtuberculum, transsellar, transclival, and transodontoid approaches. Often, a
      large skull base dural defect with a high-flow CSF leak is created after
      endoscopic skull base surgery. Successful reconstruction of the cranial base
      defect is paramount to separate the intracranial contents from the paranasal
      sinus contents and to prevent postoperative CSF leakage. The vascularized
      pedicled nasoseptal flap (PNSF) has become the workhorse for cranial base
      reconstruction after endoscopic skull base surgery, dramatically reducing the
      rate of postoperative CSF leakage since its implementation. In this report, the
      authors review the surgical technique and describe the operative nuances and
      lessons learned for successful multilayered PNSF reconstruction of cranial base
      defects with high-flow CSF leaks created after endoscopic skull base surgery. The
      authors specifically highlight important surgical pearls that are critical for
      successful PNSF reconstruction, including target-specific flap design and
      harvesting, pedicle preservation, preparation of bony defect and graft site to
      optimize flap adherence, multilayered closure technique, maximization of the
      reach of the flap, final flap positioning, and proper bolstering and buttressing
      of the PNSF to prevent flap dehiscence. Using this technique in 93 patients, the
      authors' overall postoperative CSF leak rate was 3.2%. An illustrative
      intraoperative video demonstrating the reconstruction technique is also
      presented.

PMID- 22655695
TI  - Surgical management of temporal meningoencephaloceles, cerebrospinal fluid leaks,
      and intracranial hypertension: treatment paradigm and outcomes.
AB  - OBJECT: Thinning of the tegmen tympani and mastoideum components of the temporal
      bone may predispose to the development of meningoencephaloceles and spontaneous
      CSF leaks. Surgical repair of these bony defects and associated
      meningoencephaloceles aids in the prevention of progression and meningitis.
      Intracranial hypertension may be a contributing factor to this disorder and must
      be fully evaluated and treated when present. The purpose of this study was to
      establish a treatment paradigm for tegmen defects and elucidate causative
      factors. METHODS: The authors conducted a retrospective review of 23 patients
      undergoing a combined mastoidectomy and middle cranial fossa craniotomy for the
      treatment of a tegmen defect. RESULTS: The average body mass index (BMI) among
      all patients was 33.2 +/- 7.2 kg/m(2). Sixty-five percent of the patients (15 of
      23) were obese (BMI > 30 kg/m(2)). Preoperative intracranial pressures (ICPs)
      averaged 21.8 +/- 6.0 cm H(2)O, with 10 patients (43%) demonstrating an ICP > 20
      cm H(2)O. Twenty-two patients (96%) had associated encephaloceles. Five patients
      underwent postoperative ventriculoperitoneal shunting. Twenty-two CSF leaks (96%)
      were successfully repaired at the first attempt (average follow-up 10.4 months).
      CONCLUSIONS: Among all etiologies for CSF leaks, those occurring spontaneously
      have the highest rate of recurrence. The surgical treatment of temporal bone
      defects, as well as the recognition and treatment of accompanying intracranial
      hypertension, provides the greatest success rate in preventing recurrence. After
      tegmen dehiscence repair, ventriculoperitoneal shunting should be considered for
      patients with any combination of the following high-risk factors for recurrence:
      spontaneous CSF leak not caused by another predisposing condition (that is,
      trauma, chronic infections, or prior surgery), high-volume leaks, CSF opening
      pressure > 20 cm H(2)O, BMI > 30 kg/m(2), preoperative imaging demonstrating
      additional cranial base cortical defects (that is, contralateral tegmen or
      anterior cranial base) and/or an empty sella turcica, and any history of an event
      that leads to inflammation of the arachnoid granulations and impairment of CSF
      absorption (that is, meningitis, intracranial hemorrhage, significant closed head
      injury, and so forth).

PMID- 22655697
TI  - Repair of middle fossa cerebrospinal fluid leaks using a novel combination of
      materials: technical note.
AB  - OBJECT: Methods for repairing middle fossa CSF (MFCSF) leaks have varied and
      yielded mixed results. The objective of this study was to evaluate the safety and
      durability of the authors' repair technique using a novel combination of 3
      synthetic materials. METHODS: The authors performed a retrospective case review
      of patients treated for CSF leaks between January 2009 and September 2011. Eight
      patients were found to have undergone middle fossa craniotomies for CSF leaks.
      Inclusion criteria for the study included age greater than 18 years, neuroimaging
      documented temporal bone defect, and symptoms consistent with CSF leaks or gross
      CSF otorrhea. Seven patients, 3 men and 4 women, met the inclusion criteria, and
      their charts were reviewed. Hydroxyapatite cement, collagen-based dural
      substitute matrix, and polyethylene glycol hydrogel sealant were used in all
      patients for the repair. RESULTS: In all patients the MFCSF leaks were
      successfully repaired. Initial presenting symptoms included CSF otorrhea in 4
      patients (57.1%), hearing loss in 3 (42.9%), and CSF rhinorrhea in 1 (14.3%). The
      mean follow-up duration was 12 months (range 5-33 months). In 1 patient an
      epidural hematoma developed at the operative site on postoperative Day 2, and in
      another patient a superficial wound dehiscence occurred on postoperative Day 48.
      During the follow-up period, the authors found no evidence of wound infections,
      neurovascular damage, or CSF leakage requiring reoperation. CONCLUSIONS: The
      middle fossa approach involving a combination of hydroxyapatite cement, collagen
      based dural substitute matrix, and polyethylene glycol hydrogel sealant is a
      safe, effective method for repairing MFCSF leaks. The combination of synthetic
      materials provides an alternative to existing materials for skull base surgeons.

PMID- 22655698
TI  - Skull base cerebrospinal fluid fistula.

PMID- 22655699
TI  - Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking
      and in vitro enzymatic studies.
AB  - Inhibitors of acetylcholine breakdown by acetylcholinesterase (AChE) constitute
      the main therapeutic modality for Alzheimer's disease. In the search for natural
      products with inhibitory action on AChE, this study investigated the activity of
      saffron extract and its constituents by in vitro enzymatic and molecular docking
      studies. Saffron has been used in traditional medicine against Alzheimer's
      disease. Saffron extract showed moderate AChE inhibitory activity (up to 30%),
      but IC(50) values of crocetin, dimethylcrocetin, and safranal were 96.33, 107.1,
      and 21.09 MUM, respectively. Kinetic analysis showed mixed-type inhibition, which
      was verified by in silico docking studies. Safranal interacts only with the
      binding site of the AChE, but crocetin and dimethylcrocetin bind simultaneously
      to the catalytic and peripheral anionic sites. These results reinforce previous
      findings about the beneficial action of saffron against Alzheimer's disease and
      may be of value for the development of novel therapeutic agents based on
      carotenoid-based dual binding inhibitors.

PMID- 22655700
TI  - Attomolar ultrasensitive microRNA detection by DNA-scaffolded silver-nanocluster
      probe based on isothermal amplification.
AB  - MicroRNAs (miRNAs) play vital roles in a plethora of biological and cellular
      processes. The levels of miRNAs can be useful biomarkers for cellular events or
      disease diagnosis, thus the method for sensitive and selective detection of
      miRNAs is imperative to miRNA discovery, study, and clinical diagnosis. Here we
      develop a novel method to quantify miRNA expression levels as low as attomolar
      sensitivity by target-assisted isothermal exponential amplification coupled with
      fluorescent DNA-scaffolded AgNCs and demonstrated its feasibility in the
      application of detecting miRNA in real samples. The method reveals superior
      sensitivity with a detection limit of miRNA of 2 aM synthetic spike-in target
      miRNA under pure conditions (approximately 15 copies of a miRNA molecule in a
      volume of 10 MUL) and can detect at least a 10 aM spike-in target miRNA in cell
      lysates. The method also shows the high selectivity for discriminating
      differences between miRNA family members, thus providing a promising alternative
      to standard approaches for quantitative detection of miRNA. This simple and cost
      effective strategy has a potential of becoming the major tool for simultaneous
      quantitative analysis of multiple miRNAs (biomarkers) in tissues or cells and
      supplies valuable information for biomedical research and clinical early
      diagnosis.

PMID- 22655745
TI  - A perspective on the toxicology of marine toxins.
AB  - Although there has been much progress with regard to marine toxins from
      dinoflagellates, much remains to be done. Because these compounds are a seafood
      consumer risk, the demands cover from legislative to scientific aspects.
      Legislation is required for all new toxins that appear in the coasts. On the
      other hand, it is important to understand the toxicity of the different
      analogues, in terms of both the relative toxicity to reference compounds and the
      mechanism of toxicity itself, both acute and long-term. For this, a uniform
      approach to do toxic studies is necessary, especially acute toxicity. The need
      for pure standards in sufficient supply and the understanding of the mode of
      action of some of the compounds (such as yessotoxin or azaspiracids) will help
      the development of another important field, the use of marine toxins as drug
      leads, and the chemistry around them.

PMID- 22655746
TI  - Galveston Brain Injury Conference 2010: clinical and experimental aspects of
      blast injury.
AB  - Blast injury is the most prevalent source of mortality and morbidity among
      combatants in Operations Iraqi and Enduring Freedom. Blast-induced neurotrauma
      (BINT) is a common cause of mortality, and even mild BINT may be associated with
      chronic cognitive and emotional deficits. In addition to military personnel, the
      increasing use of explosives by terrorists has resulted in growing numbers of
      blast injuries in civilian populations. Since the medical and rehabilitative
      communities are likely to be faced with increasing numbers of patients suffering
      from blast injury, the 2010 Galveston Brain Injury Conference focused on topics
      related to the diagnosis, treatment, and mechanisms of BINT. Although past
      military actions have resulted in large numbers of blast casualties, BINT is
      considered the signature injury of the conflicts in Iraq and Afghanistan. The
      attention focused on BINT has led to increased financial support for research on
      blast effects, contributing to the development of better experimental models of
      blast injury and a clearer understanding of the mechanisms of BINT. This more
      thorough understanding of blast injury mechanisms will result in novel and more
      effective therapeutic and rehabilitative strategies designed to reduce injury and
      facilitate recovery, thereby improving long-term outcomes in patients suffering
      from the devastating and often lasting effects of BINT. The following is a
      summary of the 2010 Galveston Brain Injury Conference, that included
      presentations related to the diagnosis and treatment of acute BINT, the
      evaluation of the long-term neuropsychological effects of BINT, summaries of
      current experimental models of BINT, and a debate about the relative importance
      of primary blast effects on the acute and long-term consequences of blast
      exposure.

PMID- 22655748
TI  - Dynamical systems analysis of spike-adding mechanisms in transient bursts.
AB  - Transient bursting behaviour of excitable cells, such as neurons, is a common
      feature observed experimentally, but theoretically, it is not well understood. We
      analyse a five-dimensional simplified model of after-depolarisation that exhibits
      transient bursting behaviour when perturbed with a short current injection. Using
      one-parameter continuation of the perturbed orbit segment formulated as a well
      posed boundary value problem, we show that the spike-adding mechanism is a canard
      like transition that has a different character from known mechanisms for periodic
      burst solutions. The biophysical basis of the model gives a natural time-scale
      separation, which allows us to explain the spike-adding mechanism using geometric
      singular perturbation theory, but it does not involve actual bifurcations as for
      periodic bursts. We show that unstable sheets of the critical manifold, formed by
      saddle equilibria of the system that only exist in a singular limit, are
      responsible for the spike-adding transition; the transition is organised by the
      slow flow on the critical manifold near folds of this manifold. Our analysis
      shows that the orbit segment during the spike-adding transition includes a fast
      transition between two unstable sheets of the slow manifold that are of saddle
      type. We also discuss a different parameter regime where the presence of
      additional saddle equilibria of the full system alters the spike-adding
      mechanism.

PMID- 22655749
TI  - Designing allosteric control into enzymes by chemical rescue of structure.
AB  - Ligand-dependent activity has been engineered into enzymes for purposes ranging
      from controlling cell morphology to reprogramming cellular signaling pathways.
      Where these successes have typically fused a naturally allosteric domain to the
      enzyme of interest, here we instead demonstrate 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. We present two examples, W33G
      in a beta-glycosidase enzyme (beta-gly) and W492G in a beta-glucuronidase enzyme
      (beta-gluc), in which we engineer indole-dependent activity into enzymes by
      removing a buried tryptophan side chain that serves as a buttress for the active
      site architecture. In both cases, we observe a loss of function, and in both
      cases we find that the subsequent addition of indole can be used to restore
      activity. Through a detailed analysis of beta-gly W33G kinetics, we demonstrate
      that this rescued enzyme is fully functionally equivalent to the corresponding
      wild-type enzyme. We then present the apo and indole-bound crystal structures of
      beta-gly W33G, which together establish the structural basis for enzyme
      inactivation and rescue. Finally, we use this designed switch to modulate beta
      glycosidase activity in living cells using indole. Disruption and recovery of
      protein structure may represent a general technique for introducing allosteric
      control into enzymes, and thus may serve as a starting point for building a
      variety of bioswitches and sensors.

PMID- 22655750
TI  - Ferroelectric memory based on nanostructures.
AB  - In the past decades, ferroelectric materials have attracted wide attention due
      to their applications in nonvolatile memory devices (NVMDs) rendered by the
      electrically switchable spontaneous polarizations. Furthermore, the combination
      of ferroelectric and nanomaterials opens a new route to fabricating a nanoscale
      memory device with ultrahigh memory integration, which greatly eases the ever
      increasing scaling and economic challenges encountered in the traditional
      semiconductor industry. In this review, we summarize the recent development of
      the nonvolatile ferroelectric field effect transistor (FeFET) memory devices
      based on nanostructures. The operating principles of FeFET are introduced first,
      followed by the discussion of the real FeFET memory nanodevices based on oxide
      nanowires, nanoparticles, semiconductor nanotetrapods, carbon nanotubes, and
      graphene. Finally, we present the opportunities and challenges in nanomemory
      devices and our views on the future prospects of NVMDs.

PMID- 22655755
TI  - Academic press, inc.

PMID- 22655756
TI  - Where You Can Learn More About What's New in the Chemistry of Non-Nuclear Energy
      Sources.

PMID- 22655747
TI  - Insights into the evolution of mammalian telomerase: platypus TERT shares
      similarities with genes of birds and other reptiles and localizes on sex
      chromosomes.
AB  - BACKGROUND: The TERT gene encodes the catalytic subunit of the telomerase complex
      and is responsible for maintaining telomere length. Vertebrate telomerase has
      been studied in eutherian mammals, fish, and the chicken, but less attention has
      been paid to other vertebrates. The platypus occupies an important evolutionary
      position, providing unique insight into the evolution of mammalian genes. We
      report the cloning of a platypus TERT (OanTERT) ortholog, and provide a
      comparison with genes of other vertebrates. RESULTS: The OanTERT encodes a
      protein with a high sequence similarity to marsupial TERT and avian TERT. Like
      the TERT of sauropsids and marsupials, as well as that of sharks and echinoderms,
      OanTERT contains extended variable linkers in the N-terminal region suggesting
      that they were present already in basal vertebrates and lost independently in ray
      finned fish and eutherian mammals. Several alternatively spliced OanTERT variants
      structurally similar to avian TERT variants were identified. Telomerase activity
      is expressed in all platypus tissues like that of cold-blooded animals and murine
      rodents. OanTERT was localized on pseudoautosomal regions of sex chromosomes
      X3/Y2, expanding the homology between human chromosome 5 and platypus sex
      chromosomes. Synteny analysis suggests that TERT co-localized with sex-linked
      genes in the last common mammalian ancestor. Interestingly, female platypuses
      express higher levels of telomerase in heart and liver tissues than do males.
      CONCLUSIONS: OanTERT shares many features with TERT of the reptilian outgroup,
      suggesting that OanTERT represents the ancestral mammalian TERT. Features
      specific to TERT of eutherian mammals have, therefore, evolved more recently
      after the divergence of monotremes.

PMID- 22655751
TI  - Stability of the stationary solutions of neural field equations with propagation
      delays.
AB  - In this paper, we consider neural field equations with space-dependent delays.
      Neural fields are continuous assemblies of mesoscopic models arising when
      modeling macroscopic parts of the brain. They are modeled by nonlinear integro
      differential equations. We rigorously prove, for the first time to our knowledge,
      sufficient conditions for the stability of their stationary solutions. We use two
      methods 1) the computation of the eigenvalues of the linear operator defined by
      the linearized equations and 2) the formulation of the problem as a fixed point
      problem. The first method involves tools of functional analysis and yields a new
      estimate of the semigroup of the previous linear operator using the eigenvalues
      of its infinitesimal generator. It yields a sufficient condition for stability
      which is independent of the characteristics of the delays. The second method
      allows us to find new sufficient conditions for the stability of stationary
      solutions which depend upon the values of the delays. These conditions are very
      easy to evaluate numerically. We illustrate the conservativeness of the bounds
      with a comparison with numerical simulation.

PMID- 22655758
TI  - Contributors submitting Research papers, Critical.

PMID- 22655759
TI  - The flight from regulations.

PMID- 22655761
TI  - Assessment software.

PMID- 22655760
TI  - Algae removal.

PMID- 22655762
TI  - Organic pollutant sorption on humic matter.

PMID- 22655763
TI  - Fate prediction.

PMID- 22655764
TI  - Soil lead near a battery recycling site.

PMID- 22655766
TI  - Value of uncertainty.

PMID- 22655765
TI  - Environmental justice.

PMID- 22655767
TI  - Perception differences.

PMID- 22655768
TI  - Disposal alternatives.

PMID- 22655769
TI  - Stay ahead of the curve.

PMID- 22655771
TI  - S02 implementation.

PMID- 22655770
TI  - SAB sets up dioxin panels.

PMID- 22655772
TI  - Cement kiln dust exemption.

PMID- 22655774
TI  - Medical incinerator rule.

PMID- 22655773
TI  - Authors, reviewers, and potential contributors.

PMID- 22655775
TI  - More brownfield city grants.

PMID- 22655776
TI  - New database on characterization technology.

PMID- 22655777
TI  - Now get all the product.

PMID- 22655778
TI  - Laboratory accreditation conference declared a success.

PMID- 22655779
TI  - Risk assessment commission working to define scope.

PMID- 22655781
TI  - Sediment cleanup demonstration planned for NY/NJ harbor.

PMID- 22655780
TI  - Tropospheric ozone research plan set for North America.

PMID- 22655782
TI  - DOE seeks subsurface barrier verification technology.

PMID- 22655783
TI  - Europe to toughen drinking-water standards.

PMID- 22655784
TI  - Governors push for Clean Air Act relief.

PMID- 22655785
TI  - Federal environmental justice plans go to Clinton.

PMID- 22655786
TI  - Briefs.

PMID- 22655787
TI  - Drinking recycled wastewater.

PMID- 22655788
TI  - Lean times ahead for environmental r&d funding.

PMID- 22655790
TI  - Analytical products.

PMID- 22655789
TI  - Status of ambient measurement methods for hazardous air pollutants.

PMID- 22655792
TI  - Classified section.

PMID- 22655794
TI  - Index to the advertisers in this issue.

PMID- 22655793
TI  - Professional consu ltants services directory.

PMID- 22655795
TI  - Anisotropic fibrous scaffolds for articular cartilage regeneration.
AB  - Articular cartilage lesions, which can progress to osteoarthritis, are a
      particular challenge for regenerative medicine strategies, as cartilage function
      stems from its complex depth-dependent microstructural organization, mechanical
      properties, and biochemical composition. Fibrous scaffolds offer a template for
      cartilage extracellular matrix production; however, the success of homogeneous
      scaffolds is limited by their inability to mimic the cartilage's zone-specific
      organization and properties. We fabricated trilaminar scaffolds by sequential
      electrospinning and varying fiber size and orientation in a continuous construct,
      to create scaffolds that mimicked the structural organization and mechanical
      properties of cartilage's collagen fibrillar network. Trilaminar composite
      scaffolds were then compared to homogeneous aligned or randomly oriented fiber
      scaffolds to assess in vitro cartilage formation. Bovine chondrocytes
      proliferated and produced a type II collagen and a sulfated glycosaminoglycan
      rich extracellular matrix on all scaffolds. Furthermore, all scaffolds promoted
      significant upregulation of aggrecan and type II collagen gene expression while
      downregulating that of type I collagen. Compressive testing at physiological
      strain levels further demonstrated that the mechanical properties of trilaminar
      composite scaffolds approached those of native cartilage. Our results demonstrate
      that trilaminar composite scaffolds mimic key organizational characteristics of
      native cartilage, support in vitro cartilage formation, and have superior
      mechanical properties to homogenous scaffolds. We propose that these scaffolds
      offer promise in regenerative medicine strategies to repair articular cartilage
      lesions.

PMID- 22655796
TI  - High-mobility group boxes mediate cell proliferation and radiosensitivity via
      retinoblastoma-interaction-dependent and -independent mechanisms.
AB  - Our previous studies have shown that high-mobility group box 1 (HMGB1) could
      physically associate with the retinoblastoma (RB) protein via an LXCXE (leucine-X
      cysteine-X-glutamic; X=any amino acid) motif. An identical LXCXE motif is present
      in the HMGB1-3 protein sequences, whereas a near-consensus LXCXD (leucine-X
      cysteine-X-asparagine; X=any amino acid) motif is found in the HMGB4 protein. In
      this study, we have demonstrated that like HMGB1, HMGB2-3 also associated with
      the RB in vitro and in vivo, as evidenced by glutathione-s-transferase capture
      and immunoprecipitation-Western blot assays. A point mutation of the LXCXE or
      LXCXD motif led to disruption of RB:HMGB1-4 interactions. Enforced expression of
      HMGB1-3 or HMGB4 by adenoviral-vector-mediated gene transfer resulted in
      significant inhibition of breast cancer cell proliferation through an LXCXE- or
      LXCXD-dependent mechanism and an increased radiosensitivity through an LXCXE- or
      LXCXD-independent mechanism. These results suggest an important role of the
      LXCXE/D motif in RB:HMGB1-4 association and modulation of cancer cell growth, but
      not radiosensitivity.

PMID- 22655797
TI  - Transglutaminase catalyzed cross-linking of sodium caseinate improves oxidative
      stability of flaxseed oil emulsion.
AB  - Sodium caseinate was modified by transglutaminase catalyzed cross-linking
      reaction prior to the emulsification process in order to study the effect of
      cross-linking on the oxidative stability of protein stabilized emulsions. The
      extent of the cross-linking catalyzed by different dosages of transglutaminase
      was investigated by following the ammonia production during the reaction and
      using SDS-PAGE gel. O/W emulsions prepared with the cross-linked and non-cross
      linked sodium caseinates were stored for 30 days under the same conditions.
      Peroxide value measurement, oxygen consumption measurement, and headspace gas
      chromatography analysis were used to study the oxidative stability of the
      emulsions. The emulsion made of the cross-linked sodium caseinate showed an
      improved oxidative stability with reduced formation of fatty acid hydroperoxides
      and volatiles and a longer period of low rate oxygen consumption. The improving
      effect of transglutaminase catalyzed cross-linking could be most likely
      attributed to the enhanced physical stability of the interfacial protein layer
      against competitive adsorption by oil oxidation products.

PMID- 22655854
TI  - Investigation of the reaction impurities associated with methylamphetamine
      synthesized using the Nagai method.
AB  - The synthesis of methylamphetamine hydrochloride from l-ephedrine or d
      pseudoephedrine hydrochloride via reduction with hydriodic acid and red
      phosphorus was investigated. Eighteen batches of methylamphetamine hydrochloride
      were synthesized in six replicate batches using three different reaction times.
      This allowed the investigation of the variation of impurities in the final
      product with reaction time. The results obtained have resolved previously
      conflicting impurity profile data reported in the literature for this synthesis
      route. The impurity profile was shown to change with reaction time, and all
      previously reported impurity components were identified but not in all batches.
      Additionally, 20 batches of methylamphetamine hydrochloride were synthesized from
      either from l-ephedrine or d-pseudoephedrine hydrochloride in reactions which
      were allowed to proceed for 24 h. The impurities present in the resulting batches
      were investigated, and route-specific impurities present in all batches were
      identified. Batch-to-batch fluctuations in the resultant chromatographic impurity
      profile, despite careful synthetic monitoring and control, were also noted.

PMID- 22655856
TI  - Multiphase halogen chemistry in the tropical Atlantic Ocean.
AB  - We used a one-dimensional model to simulate the chemical evolution of air masses
      in the tropical Atlantic Ocean, with a focus on halogen chemistry. The model
      results were compared to the observations of inorganic halogen species made in
      this region. The model could largely reproduce the measurements of most chlorine
      species, especially under unpolluted conditions, but overestimated sea salt
      chloride, BrCl, and bromine species. Agreement with the measurements could be
      improved by taking into account the reactivity with aldehydes and the effects of
      dimethyl sulfide (DMS) and Saharan dust on aerosol pH; a hypothetical HOX -> X(-)
      aqueous-phase reaction could also improve the agreement with measured Cl(2) and
      HOCl, especially under semipolluted conditions. The results also showed that
      halogens speciation and concentrations are very sensitive to cloud processing.
      The model was used to calculate the impact of the observed levels of halogens: Cl
      atoms accounted for 5.4-11.6% of total methane sinks and halogens (mostly bromine
      and iodine) accounted for 35-40% of total ozone destruction.

PMID- 22655855
TI  - Characterization of whole genome amplified (WGA) DNA for use in genotyping assay
      development.
AB  - BACKGROUND: Genotyping assays often require substantial amounts of DNA. To
      overcome the problem of limiting amounts of available DNA, Whole Genome
      Amplification (WGA) methods have been developed. The multiple displacement
      amplification (MDA) method using Phi29 polymerase has become the preferred choice
      due to its high processivity and low error rate. However, the uniformity and
      fidelity of the amplification process across the genome has not been extensively
      characterized. RESULTS: To assess amplification uniformity, we used array-based
      comparative genomic hybridization (aCGH) to evaluate DNA copy number variations
      (CNVs) in DNAs amplified by two MDA kits: GenomiPhi and REPLI-g. The Agilent
      Human CGH array containing nearly one million probes was used in this study
      together with DNAs from a normal subject and 2 cystic fibrosis (CF) patients.
      Each DNA sample was amplified 4 independent times and compared to its native
      unamplified DNA. Komogorov distances and Phi correlations showed a high
      consistency within each sample group. Less than 2% of the probes showed more than
      2-fold CNV introduced by the amplification process. The two amplification kits,
      REPLI-g and GenomiPhi, generate very similar amplified DNA samples despite the
      differences between the unamplified and amplified DNA samples. The results from
      aCGH analysis indicated that there were no obvious CNVs in the CFTR gene region
      due to WGA when compared to unamplified DNA. This was confirmed by quantitative
      real-time PCR copy number assays at 10 locations within the CFTR gene. DNA
      sequencing analysis of a 2-kb region within the CFTR gene showed no mutations
      introduced by WGA. CONCLUSION: The relatively high uniformity and consistency of
      the WGA process, coupled with the low replication error rate, suggests that WGA
      DNA may be suitable for accurate genotyping. Regions of the genome that were
      consistently under-amplified were found to contain higher than average GC
      content. Because of the consistent differences between the WGA DNA and the native
      unamplified DNA, characterization of the genomic region of interest, as described
      here, will be necessary to ensure the reliability of genotyping results from WGA
      DNA.

PMID- 22655858
TI  - Ultrafast charge separation and long-lived charge separated state in
      photocatalytic CdS-Pt nanorod heterostructures.
AB  - Colloidal semiconductor-metal nanoheterostructures that combine the light
      harvesting ability of semiconductor nanocrystals with the catalytic activity of
      small metal nanoparticles show promising applications for photocatalysis,
      including light-driven H(2) production. The exciton in the semiconductor domain
      can be quenched by electron-, hole-, and energy transfer to the metal particle,
      and the competition between these processes determines the photocatalytic
      efficiency of these materials. Using ultrafast transient absorption spectroscopy,
      we show that, in CdS-Pt heterostructures consisting of a CdS nanorod with a Pt
      nanoparticle at one end, the excitons in the CdS domain dissociate by ultrafast
      electron transfer (with a half-life of ~3.4 ps) to the Pt. The charge separated
      state is surprisingly long-lived (with a half-life of ~1.2 +/- 0.6 MUs) due to
      the trapping of holes in CdS. The asymmetry in the charge separation and
      recombination times is believed to be the key feature that enables the
      accumulation of the transferred electrons in the Pt tip and photocatalysis in the
      presence of sacrificial hole acceptors.

PMID- 22655859
TI  - Analysis of stability and bifurcations of fixed points and periodic solutions of
      a lumped model of neocortex with two delays.
AB  - A lumped model of neural activity in neocortex is studied to identify regions of
      multi-stability of both steady states and periodic solutions. Presence of both
      steady states and periodic solutions is considered to correspond with
      epileptogenesis. The model, which consists of two delay differential equations
      with two fixed time lags is mainly studied for its dependency on varying
      connection strength between populations. Equilibria are identified, and using
      linear stability analysis, all transitions are determined under which both
      trivial and non-trivial fixed points lose stability. Periodic solutions arising
      at some of these bifurcations are numerically studied with a two-parameter
      bifurcation analysis.

PMID- 22655860
TI  - Thickness dependency of field emission in amorphous and nanostructured carbon
      thin films.
AB  - Thickness dependency of the field emission of amorphous and nanostructured
      carbon thin films has been studied. It is found that in amorphous and carbon
      films with nanometer-sized sp2 clusters, the emission does not depend on the film
      thickness. This further proves that the emission happens from the surface sp2
      sites due to large enhancement of electric field on these sites. However, in the
      case of carbon films with nanocrystals of preferred orientation, the emission
      strongly depends on the film thickness. sp2-bonded nanocrystals have higher
      aspect ratio in thicker films which in turn results in higher field enhancement
      and hence easier electron emission.

PMID- 22655857
TI  - Dissociated predegenerated peripheral nerve transplants for spinal cord injury
      repair: a comprehensive assessment of their effects on regeneration and
      functional recovery compared to Schwann cell transplants.
AB  - Several recent studies suggest that predegenerated nerves (PDNs) or dissociated
      PDNs (dPDNs) can improve behavioral and histological outcomes following
      transplantation into the injured rat spinal cord. In the current study we tested
      the efficacy of dPDN transplantation by grafting cells isolated from the sciatic
      nerve 7 days after crush. We did not replicate one study, but rather assessed
      what appeared, based on five published reports, to be a reported robust effect of
      dPDN grafts on corticospinal tract (CST) regeneration and locomotor recovery.
      Using a standardized rodent spinal cord injury model (200 kD IH contusion) and
      transplantation procedure (injection of GFP+ cells 7 days post-SCI), we
      demonstrate that dPDN grafts survive within the injured spinal cord and promote
      the ingrowth of axons to a similar extent as purified Schwann cell (SC) grafts.
      We also demonstrate for the first time that while both dPDN and SC grafts promote
      the ingrowth of CGRP axons, neither graft results in mechanical or thermal
      hyperalgesia. Unlike previous studies, dPDN grafts did not promote long-distance
      axonal growth of CST axons, brainstem spinal axons, or ascending dorsal column
      sensory axons. Moreover, using a battery of locomotor tests (Basso Beattie
      Bresnahan [BBB] score, BBB subscore, inked footprint, Catwalk, and ladderwalk),
      we failed to detect any beneficial effects of dPDN transplantation on the
      recovery of locomotor function after SCI. We conclude that dPDN transplants are
      not sufficient to promote CST regeneration or locomotor recovery after SCI.

PMID- 22655861
TI  - Synthesis of highly functionalized 9,10-phenanthrenequinones by oxidative
      coupling using MoCl5.
AB  - The strong oxidative power of molybdenum pentachloride gives rise to an efficient
      oxidative C-C bond formation of benzil derivatives to the corresponding 9,10
      phenanthrenequinones. A highly complementary method to previous approaches was
      developed. The required derivatives are accessible in a modular fashion and in
      excellent yields. By this approach the orchid-derived natural product
      cypripediquinone A was synthesized for the first time.

PMID- 22655863
TI  - Short courses.

PMID- 22655862
TI  - Diffusion laws in dendritic spines.
AB  - Dendritic spines are small protrusions on a neuronal dendrite that are the main
      locus of excitatory synaptic connections. Although their geometry is variable
      over time and along the dendrite, they typically consist of a relatively large
      head connected to the dendritic shaft by a narrow cylindrical neck. The surface
      of the head is connected smoothly by a funnel or non-smoothly to the narrow neck,
      whose end absorbs the particles at the dendrite. We demonstrate here how the
      geometry of the neuronal spine can control diffusion and ultimately synaptic
      processes. We show that the mean residence time of a Brownian particle, such as
      an ion or molecule inside the spine, and of a receptor on its membrane, prior to
      absorption at the dendritic shaft depends strongly on the curvature of the
      connection of the spine head to the neck and on the neck's length. The analytical
      results solve the narrow escape problem for domains with long narrow necks.

PMID- 22655864
TI  - Discover chemistry from Japan.

PMID- 22655866
TI  - Landfill plume monitoring.

PMID- 22655867
TI  - Ozone pretreatment.

PMID- 22655868
TI  - Metal in tree rings.

PMID- 22655870
TI  - Determining solubility.

PMID- 22655869
TI  - Methane consumption.

PMID- 22655871
TI  - Measuring amino acids.

PMID- 22655872
TI  - Removing heavy metals with phytoextraction.

PMID- 22655873
TI  - Sludge application.

PMID- 22655874
TI  - Solvents in groundwater.

PMID- 22655875
TI  - Mechanistic modeling.

PMID- 22655877
TI  - Cultural differences.

PMID- 22655876
TI  - Global warming beliefs.

PMID- 22655878
TI  - Explosives treatment.

PMID- 22655879
TI  - Immobilizing lead.

PMID- 22655880
TI  - Extracellular enzymes.

PMID- 22655881
TI  - Authors, reviewers, and potential contributors.

PMID- 22655882
TI  - Banking in wetlands.

PMID- 22655883
TI  - Eight-hour ozone standards proposed.

PMID- 22655884
TI  - EPA methods and ion trap mass spectrometry.

PMID- 22655885
TI  - Clinton offers regulatory reforms as Congress hammers out bills.

PMID- 22655887
TI  - Study identifies sources of airborne dioxin in Great Lakes.

PMID- 22655886
TI  - Water monitoring strategy begun.

PMID- 22655888
TI  - EPA's R&D "reinvention" endorsed.

PMID- 22655889
TI  - "Starving" microbes degrade TCE, but applications limited.

PMID- 22655890
TI  - EPA considers new contaminated sediments initiative.

PMID- 22655891
TI  - International carbon dioxide trading proposed by UN agency.

PMID- 22655893
TI  - Manufacturers lead new reference materials program.

PMID- 22655892
TI  - DOE cleanup agreements criticized as "unrealistic".

PMID- 22655894
TI  - Briefs.

PMID- 22655895
TI  - Now get all the product.

PMID- 22655896
TI  - New analytical instruments at pittcon '95.

PMID- 22655897
TI  - On-Line, In Situ Analysis with Membrane Introduction MS.

PMID- 22655899
TI  - Exploiting opportunities for pollution prevention in EPA enforcement agreements.

PMID- 22655898
TI  - Journal of chemical information and computer sciences.

PMID- 22655900
TI  - Analytical products.

PMID- 22655902
TI  - Classified section.

PMID- 22655903
TI  - Professional consultants services directory.

PMID- 22655904
TI  - Index to the advertisers in this issue.

PMID- 22655905
TI  - Synthesis of symmetrical and unsymmetrical N,N'-diaryl guanidines via copper/N
      methylglycine-catalyzed arylation of guanidine nitrate.
AB  - CuI/N-methylglycine-catalyzed coupling reaction of guanidine nitrate with both
      aryl iodides and bromides takes place at 70-100  degrees C, affording symmetrical
      N,N'-diaryl guanidines with good to excellent yields. Unsymmetrical N,N'-diaryl
      guanidines can be assembled via monoarylation of guanidine nitrate with aryl
      iodides bearing a strong electron-withdrawing group and subsequent coupling with
      another aryl iodide.

PMID- 22655909
TI  - Circulating Th17 cells are not elevated in patients with chronic heart failure.
AB  - BACKGROUND: Increasing evidences have been obtained that immune activation and
      inflammation play critical roles in the pathogenesis of chronic heart failure
      (CHF). T helper (Th) 17 cells are a newly found pro-inflammatory T cell subtype.
      We therefore assessed the hypothesis that circulating Th17 cells increased in
      patients with CHF. Hypothesis. Th17 cells and its cytokine might be elevated in
      patients with CHF. METHODS: A total of 92 patients with CHF and 59 healthy donors
      were enrolled in the study. The frequencies of circulating Th17 cells were
      determined by flow cytometry. The interleukin (IL)-17 protein levels in the serum
      and supernatant of phytohemagglutinin (PHA)-stimulated periphery blood
      mononuclear cells (PBMCs) were detected using ELISA and the mRNA expression of
      retinoic acid-related orphan receptor (ROR)gammat, which is the key transcription
      factor of Th17 cells was measured by RT-PCR. RESULTS: There were no significant
      differences in the frequency of circulating Th17 cells, serum level of IL-17, and
      expression of RORgammat in PBMCs between CHF patients and healthy controls. IL-17
      protein level in the supernatants of PHA-stimulated PBMCs was also comparable
      between CHF patients and health donors. CONCLUSIONS: Circulating Th17 cells are
      not elevated in patients with CHF.

PMID- 22655910
TI  - Periodontal and systemic responses in various mice models of experimental
      periodontitis: respective roles of inflammation duration and Porphyromonas
      gingivalis infection.
AB  - BACKGROUND: The great variability of periodontal and systemic responses to
      experimental periodontitis reflects the inherent pathogenic complexity of mice
      models and could limit the resulting interpretations and their extension to human
      diseases. This study compared the effect of Porphyromonas gingivalis (Pg)
      infection and experimental periodontitis duration at local and systemic levels in
      various models. METHODS: Periodontitis was induced in C57BL/6J mice by ligatures
      previously incubated with Pg (LIGPG group) or not (LIG group) or by oral gavage
      (GAV) with Pg ATCC 33277. Blood samples were taken, and mice were euthanized at
      different times. Periodontal tissue destruction, osteoclast number, and
      inflammation were assessed by histomorphometry, tartrate-resistant acid
      phosphatase histoenzymology, and cathepsin B (CATB) and matrix metalloproteinase
      9 (MMP9) immunochemistry. Serum levels of interleukin-6 (IL-6) and IL-1beta were
      measured using enzyme-linked immunosorbent assay bioplex methods. RESULTS:
      Periodontal tissue destruction and osteoclast numbers were significantly elevated
      in LIGPG models compared to LIG and GAV models. They increased with time with the
      exception of osteoclast numbers in the LIG model. CATB and MMP9 expression was
      related to bone destruction processes and Pg infection. The highest serum levels
      of IL-6 and IL-1beta were observed in the LIGPG group. A decrease of IL-6 and an
      increase of IL-1beta serum level were observed with time in LIGPG group contrary
      to LIG group. CONCLUSIONS: These data indicate that Pg infection worsened
      periodontal tissue destruction through specific pathogenic pathways and modified
      systemic response to periodontal inflammation. Furthermore, the blood cytokine
      response to ligature models showed their relevance for evaluating the systemic
      impact of periodontal disease.

PMID- 22655911
TI  - Locally Delivered 0.5% Azithromycin as an Adjunct to Non-Surgical Treatment in
      Patients With Chronic Periodontitis With Type 2 Diabetes: A Randomized Controlled
      Clinical Trial.
AB  - BACKGROUND: Several epidemiologic studies have identified a greater incidence of
      periodontitis in patients with type 2 diabetes. Recent developments suggest that
      local delivery of antimicrobials into periodontal pockets improve periodontal
      health. The present study is designed to investigate the adjunctive effects of
      subgingivally delivered azithromycin (AZM; 0.5% concentration) as an adjunct to
      scaling and root planing (SRP) for treating chronic periodontitis in patients
      with type 2 diabetes. METHODS: A total of 63 patients were categorized into two
      treatment groups: 1) group 1: SRP + placebo gel and 2) group 2: SRP + 0.5% AZM.
      Clinical parameters were recorded at baseline and 3, 6, and 9 months; they
      included modified sulcus bleeding index (mSBI), plaque index (PI), probing depth
      (PD), and clinical attachment level (CAL). RESULTS: Both therapies resulted in
      significant improvements. Using a patient-based analysis, patients in group 2
      treated with SRP + 0.5% AZM showed enhanced reductions in PI, GI, mSBI, and PD
      and gains in CAL (P <0.05) over 9 months compared with group 1. CONCLUSION:
      Although both treatment strategies seem to benefit the patients, the adjunctive
      use of 0.5% AZM as a controlled drug delivery system enhances the clinical
      outcome.

PMID- 22655912
TI  - Glyceollins, soy isoflavone phytoalexins, improve oral glucose disposal by
      stimulating glucose uptake.
AB  - Soy glyceollins, induced during stress, have been shown to inhibit cancer cell
      growth in vitro and in vivo. In the present study, we used prediabetic rats to
      examine the glyceollins effect on blood glucose. During an oral glucose tolerance
      test (OGTT), the blood glucose excursion was significantly decreased in the rats
      treated with oral administration of either 30 or 90 mg/kg glyceollins. Plasma
      analysis demonstrated that glyceollins are absorbed after oral administration,
      and duration of exposure extends from 20 min to at least 4 h postadministration.
      Exposure of 3T3-L1 adipocytes to glyceollins significantly increased both insulin
      stimulated and basal glucose uptake. Basal glucose uptake was increased 1.5-fold
      by exposure to 5 MUM glyceollin in a dose-response manner. Coincubation with
      insulin significantly stimulated maximal glucose uptake above basal uptake levels
      and tended to increase glucose uptake beyond the levels of either stimulus alone.
      On a molecular level, polymerase chain reaction showed significantly increased
      levels of glucose transporter GLUT4 mRNA in 3T3-L1 adipocytes, especially when
      the cells were exposed to 5 MUM glyceollins for 3 h in vitro. It correlated with
      elevated protein levels of GLUT4 detected in the 5 MUM glyceollin-treated cells.
      Thus, the simulative effect of the glyceollins on adipocyte glucose uptake was
      attributed to up-regulation of glucose transporters. These findings indicate
      potential benefits of the glyceollins as an intervention in prediabetic
      conditions as well as a treatment for type 1 and type 2 diabetes by increasing
      both the insulin-mediated and the basal, insulin-independent, glucose uptake by
      adipocytes.

PMID- 22655913
TI  - Oxidative stress in growth hormone transgenic coho salmon with compressed
      lifespan--a model for addressing aging.
AB  - Growth hormone (GH) transgenic fish have dramatically enhanced growth rates,
      increased oxygen demands and reactive oxygen species production. GH-transgenic
      coho salmon provide an opportunity to address effects of increased metabolism on
      physiological aging. The objective of this study was to compare oxidative stress
      in wild-type (WT) and GH-transgenic (T) coho salmon (Oncorhynchus kisutch) of
      different ages (1 and 2 years). Antioxidant enzyme activity, protein carbonyls
      (PC) and glutathione (GSH, GSSG) were measured. PC correlated to growth rates in
      individual fish. T fish exhibited lower antioxidant enzyme activities and GSH
      levels compared to the WT, while levels of PC and GSSG were higher. Age affects
      were observed in both WT and T fish; enzyme activities and GSH decreased while PC
      and GSSG increased. Our results support the metabolic rate theory of aging. This
      study aims to be a platform for continued studies of the theories of aging using
      fish as model organisms.

PMID- 22655914
TI  - Optical turn-on sensor based on graphene oxide for selective detection of D
      glucosamine.
AB  - By incorporating the well-known fluorophore 8-aminoquinoline into graphene oxide,
      we have successfully prepared a turn-on fluorescent sensor capable of specific
      detection of D-glucosamine with a high selectivity and sensitivity. This
      methodology provides a new concept for the design and development of highly
      selective and sensitive turn-on optical sensors for selective detection of
      aminosaccharides and many other biomolecules.

PMID- 22655966
TI  - Exploiting micelle-driven coordination to evaluate the lipophilicity of
      molecules.
AB  - We present a systematic study based on the calculation of complexation constants
      between a Zn-complex solubilized in Triton X-100 micellar solutions and a series
      of linear mono- and dicarboxylic acids, under physiological pH conditions, that
      allowed the evaluation of the lipophilicity of these molecules. This empirical
      lipophilicity parameter describes conveniently the partition of organic molecules
      between hydrophobic microdomains and water. The results can be used to predict
      the lipophilicity of molecules with similar structure and allows the distinction
      of intrinsic contributions of the carboxylates and of the methylene groups to the
      lipophilicity of the molecule.

PMID- 22655968
TI  - Targeting heparanase for cancer therapy at the tumor-matrix interface.

PMID- 22655967
TI  - Biodistribution and elimination kinetics of systemic Stx2 by the Stx2A and Stx2B
      subunit-specific human monoclonal antibodies in mice.
AB  - BACKGROUND: Hemolytic uremic syndrome (HUS) leading to acute kidney failure, is a
      condition linked to the production of primarily Shiga toxin 2 (Stx2) by some E.
      coli serotypes. We have previously shown that Stx2 A subunit-specific human
      monoclonal antibody (HuMAb) 5C12, and B subunit-specific HuMAb 5H8 inhibit
      cultured cell death, and protect mice and piglets from fatal Stx2-intoxication.
      We have also shown that 5H8 blocks binding of Stx2 to its cell-surface receptor
      globotriaosyl ceramide (Gb(3)), whereas Stx2 when complexed with 5C12 binds Gb(3)
      with higher affinity than Stx2. The mechanism by which 5C12 neutralizes Stx2 in
      vitro involves trapping of Stx2 in the recycling endosomes and releasing it into
      the extracellular environment. Because of the clinical implications associated
      with the formation of Stx2/antibody complexes and the potential for trapping and
      clearance through a severely damaged kidney associated with HUS, we investigated
      the likely site(s) of Stx2/antibody localization and clearance in intoxicated
      mice treated with antibody or placebo. RESULTS: Mice were injected with
      radiolabeled Stx2 ((125)I-Stx2) 4 hours after administration of 5C12, 5H8, or
      phosphate buffered saline (PBS) and the sites of localization of labeled Stx2,
      were investigated 3, 24 and 48 hours later. The liver recorded statistically much
      higher concentrations of labeled Stx2 for groups receiving 5C12 and 5H8
      antibodies after 3, 24 and 48 hours, as compared with the PBS group. In contrast,
      highest levels of labeled Stx2 were detected in the kidneys of the PBS group at
      all 3 sampling times. Mice receiving either of the two HuMAbs were fully
      protected against the lethal effect of Stx2, as compared with the fatal outcome
      of the control group. CONCLUSIONS: The results suggest that HuMAbs 5C12 and 5H8
      promoted hepatic accumulation and presumably clearance of toxin/antibody
      complexes, significantly diverting Stx2 localization in the kidneys, the target
      of Stx2 and the cause of HUS. This is in contrast to the fatal outcome of the
      control group receiving PBS. The results also confirm earlier observations that
      both HuMAbs are highly and equally protective against Stx2 intoxication in mice.

PMID- 22655969
TI  - Rapid clinical and radiographic improvement after intrathecal trastuzumab and
      methotrexate in a patient with HER-2 positive leptomeningeal metastases.

PMID- 22655970
TI  - Interface dynamics in planar neural field models.
AB  - Neural field models describe the coarse-grained activity of populations of
      interacting neurons. Because of the laminar structure of real cortical tissue
      they are often studied in two spatial dimensions, where they are well known to
      generate rich patterns of spatiotemporal activity. Such patterns have been
      interpreted in a variety of contexts ranging from the understanding of visual
      hallucinations to the generation of electroencephalographic signals. Typical
      patterns include localized solutions in the form of traveling spots, as well as
      intricate labyrinthine structures. These patterns are naturally defined by the
      interface between low and high states of neural activity. Here we derive the
      equations of motion for such interfaces and show, for a Heaviside firing rate,
      that the normal velocity of an interface is given in terms of a non-local Biot
      Savart type interaction over the boundaries of the high activity regions. This
      exact, but dimensionally reduced, system of equations is solved numerically and
      shown to be in excellent agreement with the full nonlinear integral equation
      defining the neural field. We develop a linear stability analysis for the
      interface dynamics that allows us to understand the mechanisms of pattern
      formation that arise from instabilities of spots, rings, stripes and fronts. We
      further show how to analyze neural field models with linear adaptation currents,
      and determine the conditions for the dynamic instability of spots that can give
      rise to breathers and traveling waves.

PMID- 22655971
TI  - Type I restriction-modification system and its resistance in electroporation
      efficiency in Flavobacterium columnare.
AB  - Flavobacterium columnare, the causative agent of columnaris disease, infects
      freshwater fish worldwide. However, the pathogenicity of this bacterium is poorly
      understood due possibly to the lack of an efficient in-frame knockout technique.
      In order to improve electroporation efficiency, the type I restriction
      modification system (R-M system) was cloned and its role in electroporation was
      examined in F. columnare G(4) strain. The complete sequence of type I R-M system
      in the bacterium, designated as Fcl, contains all three subunits of type I R-M
      system, named as fclM, fclS, fclR, respectively, with the identification of a
      hypothetical gene, fclX. Constitutive transcription of the three genes was
      observed in F. columnare G(4) by RT-PCR. The ORF of fclM and fclS was cloned into
      the plasmid pACYC184 and transformed into Escherichia coli TOP10. The resultant
      E. coli strain, designated as E. coli TOPmt, was transformed with the integrative
      plasmid pGL006 constructed for F. columnare G(4). The integrative plasmid was re
      isolated from TOPmt and incubated with the lysate of F. columnare G(4). The re
      isolated integrative plasmid, designated as pGL006', showed higher resistance
      than pGL006. With pGL006', the electroporation efficiency of the strain G(4)
      increased 2.6 times, while that of F. columnare G(18) was not obviously improved.
      Furthermore, a method to improve the electroporation efficiency of F. columnare
      G(4) was developed using the integrative plasmid methylated by E. coli TOPmt
      which contains the fclM and fclS gene of F. columnare G(4). Further analyses
      showed that the fcl gene cluster may be a unique type I R-M system in F.
      columnare G(4). It will be of significant interest to examine the composition and
      diversity of R-M systems in strains of F. columnare in order to set up a suitable
      genetic manipulation system for the bacterium.

PMID- 22655972
TI  - Cholecalciferol (vitamin D) differentially regulates antimicrobial peptide
      expression in bovine mammary epithelial cells: implications during Staphylococcus
      aureus internalization.
AB  - Vitamin D has immunomodulatory functions regulating the expression of host
      defense genes. The aim of this study was to determine the effect of
      cholecalciferol (vitamin D3) on S. aureus internalization into bovine mammary
      epithelial cells (bMEC) and antimicrobial peptide (AP) mRNA expression.
      Cholecalciferol (1-200 nM) did not affect S. aureus growth and bMEC viability;
      but it reduced bacterial internalization into bMEC (15-74%). Also, bMEC showed a
      basal expression of all AP genes evaluated, which were induced by S. aureus.
      Cholecalciferol alone or together with bacteria diminished tracheal antimicrobial
      peptide (TAP) and bovine neutrophil beta-defensin (BNBD) 5 mRNA expression; while
      alone induced the expression of lingual antimicrobial peptide (LAP), bovine beta
      defensin 1 (DEFB1) and bovine psoriasin (S100A7), which was inhibited in the
      presence of S. aureus. This compound (50 nM) increased BNBD10 mRNA expression
      coinciding with the greatest reduction in S. aureus internalization. Genes of
      vitamin D pathway (25-hydroxylase and 1 alpha-hydroxylase) show basal expression,
      which was induced by cholecalciferol or bacteria. S. aureus induced vitamin D
      receptor (VDR) mRNA expression, but not in the presence of cholecalciferol. In
      conclusion, cholecalciferol can reduce S. aureus internalization and
      differentially regulates AP expression in bMEC. Thus, vitamin D could be an
      effective innate immunity modulator in mammary gland, which leads to a better
      defense against bacterial infection.

PMID- 22655973
TI  - Discrepancy between minimal inhibitory concentration to enrofloxacin and
      mutations present in the quinolone-resistance determining regions of Mycoplasma
      gallisepticum field strains.
AB  - Molecular characterization of the quinolone-resistance determining regions
      (QRDRs) of DNA gyrase and topoisomerase IV in 93 Mycoplasma gallisepticum field
      strains isolated in different geographic regions revealed discrepancies between
      minimal inhibitory concentration values and presence of amino acid substitutions
      within the QRDRs of GyrA and ParC in 9/93 (10%) strains. This may delimitate
      applicability of a gene-based assay to detect fluoroquinolone resistance in this
      avian pathogen.

PMID- 22655974
TI  - An experimental study of Bungowannah virus infection in weaner aged pigs.
AB  - Bungowannah virus is a pestivirus identified from an outbreak of stillbirth and
      increased mortality in the first 3-4 weeks of life on a piggery in New South
      Wales, Australia in June 2003. The aims of this study were to determine if post
      natal infection results in any clinical abnormalities and quantify the amount of
      Bungowannah virus RNA in blood, oropharyngeal, nasal and conjunctival excretions
      and faeces during the course of infection. Thirty pigs were infected intra
      nasally with one of six different doses of Bungowannah virus or a control
      inoculum and clinical signs and rectal temperatures monitored. Sera, leukocytes
      and oropharyngeal, nasal, conjunctival, rectal and tissue swabs were tested for
      Bungowannah virus by qRT-PCR and sera for antibody by peroxidase linked assay and
      virus neutralisation test. The infectious dose by the intra-nasal route in weaner
      pigs was determined to be between 1.6 and 3.2 log(10) TCID(50). Few clinical
      signs could be attributed to infection. Viraemia and viral excretion in
      oropharyngeal secretions were detected from 3 days post-inoculation and
      seroconversion from 10 days post-inoculation. Viral shedding was greatest and
      most frequently detected in oropharyngeal, and to a lesser extent, nasal
      secretions, and generally detected in lower amounts and less frequently in
      conjunctival secretions and faeces.

PMID- 22655975
TI  - Characterization of methicillin-resistant Staphylococcus aureus CC398 obtained
      from humans and animals on dairy farms.
AB  - In this study MRSA isolates from dairy farms were investigated for their genetic
      relationships and antimicrobial susceptibility. In total, 125 MRSA isolates from
      26 dairy farms were studied, including isolates from milk samples (n=46), dairy
      cattle (n=24), calves (n=6), dust samples from pig (n=16) and veal calf sheds
      (n=1), dogs (n=2), a horse, a sheep and humans (n=28). CC398-specific PCRs, spa
      typing, SCCmec typing and ApaI macrorestriction analysis were conducted.
      Susceptibility testing was performed by broth microdilution. All 125 isolates
      belonged to CC398. Eight spa types (t011, t108, t034, t567, t1184, t1451, t2287
      and t3934) were detected. SCCmec elements of types IV (n=48) and V (n=67) were
      identified with 10 isolates being non-typeable. Six main macrorestriction
      patterns - with up to 23 sub-patterns - and twelve resistance patterns were
      identified. Sixty-eight isolates showed a multiresistance phenotype. Farm-by-farm
      analysis revealed different scenarios: in some farms, the MRSA CC398 isolates
      from dairy cattle, humans, pig sheds and/or sheep were indistinguishable
      suggesting an interspecies exchange of the same MRSA CC398 subtype. In other
      farms, several MRSA CC398 subtypes were detected in different host
      species/sources with occasionally even more than one MRSA CC398 subtype from the
      same host species/source. These latter results may suggest that either different
      MRSA subtypes associated with humans or animals have been imported into the
      respective farm or that one MRSA CC398 strain has undergone diversification,
      reflected by more or less expanded changes in PFGE patterns, spa type or
      resistance pattern, during colonization of different hosts on the same farm.

PMID- 22655976
TI  - Newcastle disease virus outbreaks: vaccine mismatch or inadequate application?
AB  - Newcastle disease (ND) is one of the most important diseases of poultry, and may
      cause devastating losses in the poultry industry worldwide. Its causative agent
      is Newcastle disease virus (NDV), also known as avian paramyxovirus type 1. Many
      countries maintain a stringent vaccination policy against ND, but there are
      indications that ND outbreaks can still occur despite intensive vaccination. It
      has been argued that this may be due to antigenic divergence between the vaccine
      strains and circulating field strains. Here we present the complete genome
      sequence of a highly virulent genotype VII virus (NL/93) obtained from vaccinated
      poultry during an outbreak of ND in the Netherlands in 1992-1993. Using this
      strain, we investigated whether the identified genetic evolution of NDV is
      accompanied by antigenic evolution. In this study we show that a live vaccine
      that is antigenically adapted to match the genotype VII NL/93 outbreak strain
      does not provide increased protection compared to a classic genotype II live
      vaccine. When challenged with the NL/93 strain, chickens vaccinated with a
      classic vaccine were completely protected against clinical disease and mortality
      and virus shedding was significantly reduced, even with a supposedly suboptimal
      vaccine dose. These results suggest that it is not antigenic variation but rather
      poor flock immunity due to inadequate vaccination practices that may be
      responsible for outbreaks and spreading of virulent NDV field strains.

PMID- 22655978
TI  - Gold and silver nanoparticles for biomolecule immobilization and enzymatic
      catalysis.
AB  - In this work, a simple method for alcohol synthesis with high enantiomeric
      purity was proposed. For this, colloidal gold and silver surface modifications
      with 3-mercaptopropanoic acid and cysteamine were used to generate carboxyl and
      amine functionalized gold and silver nanoparticles of 15 and 45 nm, respectively.
      Alcohol dehydrogenase from Thermoanaerobium brockii (TbADH) and its cofactor
      (NADPH) were physical and covalent (through direct adsorption and using cross
      linker) immobilized on nanoparticles' surface. In contrast to the physical and
      covalent immobilizations that led to a loss of 90% of the initial enzyme activity
      and 98% immobilization, the use of a cross-linker in immobilization process
      promoted a loss to 30% of the initial enzyme activity and >92% immobilization.
      The yield of NADPH immobilization was about 80%. The best results in terms of
      activity were obtained with Ag-citr nanoparticle functionalized with carboxyl
      groups (Ag-COOH), Au-COOH(CTAB), and Au-citr functionalized with amine groups and
      stabilized with CTAB (Au-NH2(CTAB)) nanoparticles treated with 0.7% and 1.0%
      glutaraldehyde. Enzyme conformation upon immobilization was studied using
      fluorescence and circular dichroism spectroscopies. Shift in ellipticity at 222
      nm with about 4 to 7 nm and significant decreasing in fluorescence emission for
      all bioconjugates were observed by binding of TbADH to silver/gold nanoparticles.
      Emission redshifting of 5 nm only for Ag-COOH-TbADH bioconjugate demonstrated
      change in the microenvironment of TbADH. Enzyme immobilization on glutaraldehyde
      treated Au-NH2(CTAB) nanoparticles promotes an additional stabilization
      preserving about 50% of enzyme activity after 15 days storage. Nanoparticles
      attached-TbADH-NADPH systems were used for enantioselective (ee > 99%) synthesis
      of (S)-7-hydroxy-2-tetralol.

PMID- 22655980
TI  - Size-dependent interaction of silica nanoparticles with different surfactants in
      aqueous solution.
AB  - The size-dependent interaction of anionic silica nanoparticles with ionic
      (anionic and cationic) and nonionic surfactants has been studied using small
      angle neutron scattering (SANS). The surfactants used are anionic sodium dodecyl
      sulfate (SDS), cationic dodecyltrimethyl ammonium bromide (DTAB), and nonionic
      decaoxyethylene n-dodecylether (C(12)E(10)). The measurements have been carried
      out for three different sizes of silica nanoparticles (8, 16, and 26 nm) at fixed
      concentrations (1 wt % each) of nanoparticles and surfactants. It is found that
      irrespective of the size of the nanoparticles there is no significant interaction
      evolved between like-charged nanoparticles and the SDS micelles leading to any
      structural changes. However, the strong attraction of oppositely charged DTAB
      micelles with silica nanoparticles results in the aggregation of nanoparticles.
      The number of micelles mediating the nanoparticle aggregation increases with the
      size of the nanoparticle. The aggregates are characterized by fractal structure
      where the fractal dimension is found to be constant (D ~ 2.3) independent of the
      size of the nanoparticles and consistent with diffusion-limited-aggregation-type
      fractal morphology in these systems. In the case of nonionic surfactant
      C(12)E(10), micelles interact with the individual silica nanoparticles. The
      number of adsorbed micelles per nanoparticle increases drastically whereas the
      percentage of adsorbed micelles on nanoparticles decreases with the increase in
      the size of the nanoparticles.

PMID- 22656036
TI  - Commentary on "Optimizing chimerism level through bone marrow transplantation and
      irradiation to induce long-term tolerance to composite tissue
      allotransplantation".

PMID- 22655979
TI  - Coculture strategies in bone tissue engineering: the impact of culture conditions
      on pluripotent stem cell populations.
AB  - The use of pluripotent stem cell populations for bone tissue regeneration
      provides many opportunities and challenges within the bone tissue engineering
      field. For example, coculture strategies have been utilized to mimic
      embryological development of bone tissue, and particularly the critical
      intercellular signaling pathways. While research in bone biology over the last 20
      years has expanded our understanding of these intercellular signaling pathways,
      we still do not fully understand the impact of the system's physical
      characteristics (orientation, geometry, and morphology). This review of coculture
      literature delineates the various forms of coculture systems and their respective
      outcomes when applied to bone tissue engineering. To understand fully the key
      differences between the different coculture methods, we must appreciate the
      underlying paradigms of physiological interactions. Recent advances have enabled
      us to extrapolate these techniques to larger dimensions and higher geometric
      resolutions. Finally, the contributions of bioreactors, micropatterned
      biomaterials, and biomaterial interaction platforms are evaluated to give a sense
      of the sophistication established by a combination of these concepts with
      coculture systems.

PMID- 22656037
TI  - Predicting outcomes in the setting of blunt thoracic trauma.

PMID- 22656038
TI  - Mixing it up: antibiotic cycling in the SICU.

PMID- 22656039
TI  - Hepatic resection for huge (>15 cm) multinodular HCC with macrovascular invasion.
AB  - BACKGROUND: Surgical resection has routinely not been recommended for patients
      with huge (>15 cm) multinodular lesions and macrovascular invasion (advanced
      stage hepatocellular carcinoma [HCC] patients) because of high operative
      mortality, recurrence rate, and lack of survival benefit. METHODS: A
      retrospective study of 1425 patients was carried out, of which 1245 patients met
      EASL/AASLD criteria for hepatic resection (HR-EA group), 116 were surgically
      treated advanced-stage HCC patients (HR-AS group), and 64 were advanced-stage HCC
      patients receiving nonsurgical treatments (N-AS group). CONCLUSION: HR may still
      be suitable for the HCC patients with huge (>15 cm) multinodular lesions and
      macrovascular invasion in selected cases. Advanced-stage HCC patients without
      liver cirrhosis and with a tumor-free resection margin could enjoy longer
      survival and lower recurrence. Preoperative and/or postoperative TACE provides no
      survival benefits for advanced-stage HCC patients.

PMID- 22656040
TI  - Intramyocardial transplantation of endothelial progenitor cells and
      erythropoietin: a new scope for the treatment of cardiovascular disease.

PMID- 22656041
TI  - Craniofacial repair with fetal bone grafts engineered from amniotic mesenchymal
      stem cells.
AB  - BACKGROUND: Ethically acceptable applications of fetal tissue engineering as a
      perinatal therapy can be expanded beyond life-threatening anomalies by amniotic
      fluid cell-based methods, in which cell procurement poses no additional risk to
      the mother. We sought to start to determine whether osseous grafts engineered
      from amniotic mesenchymal stem cells (aMSCs) could be an adjunct to craniofacial
      repair. METHODS: New Zealand rabbits (n = 12) underwent creation of a full
      thickness diploic nasal bone defect. We then equally divided animals into two
      groups based on how the defect was repaired: namely, size-matched implants of
      electrospun biodegradable nanofibers with or without nuclear labeled, allogeneic
      aMSCs maintained in osteogenic medium. We killed animals 8 wk post-implantation
      for multiple analyses. Statistical analysis included analysis of variance, post
      hoc Bonferroni adjusted comparisons, and Levene's F-test, as appropriate (P <
      0.05), with significance set at P < 0.05. RESULTS: Micro-computed tomography
      scanning (two- and three-dimensional) showed no significant differences in defect
      radiodensity between groups. However, extracellular calcium levels were
      significantly higher in engineered grafts than in acellular implants (P = 0.003).
      There was significantly greater variability in mineralization in acellular
      implants than in engineered grafts by both direct calcium (P = 0.008) and micro
      computed tomography measurements (P = 0.032). There were no significant
      differences in alkaline phosphatase activity or variance between groups. We
      documented labeled cells in the engineered grafts. CONCLUSIONS: Craniofacial
      repair with osseous grafts engineered from aMSCs lead to enhanced and more
      consistent mineralization compared with an equivalent acellular prosthetic
      repair. Amniotic fluid-derived engineered bone may become a practical adjunct to
      perinatal craniofacial reconstruction.

PMID- 22656042
TI  - Dispersion state and humic acids concentration-dependent sorption of pyrene to
      carbon nanotubes.
AB  - Sonication and humic acids (HA) are known to disperse carbon nanotube (CNT)
      suspensions, but potential effects on sorption of chemicals to CNTs remain poorly
      understood. We applied a passive sampling method to investigate the influence of
      dispersion/aggregation on sorption of pyrene to CNTs. Sonication broke down CNT
      aggregates and increased pyrene sorption affinity by up to 1.39 orders of
      magnitude. Sorption surfaces newly exposed by sonication remained available to
      pyrene even after reaggregation occurred, suggesting an irreversible effect of
      sonication. The presence of HA decreased sorption of pyrene to CNTs, but at the
      highest HA concentration investigated (200 mg/L), sorption affinity was still
      1.90 orders of magnitude larger than sorption of pyrene to HA alone. Specific
      interactions between pyrene and CNTs were thus still taking place, in spite of
      the presence of a HA coating on the CNTs' surface. A greater suppression of
      sorption by CNTs occurred when the HA addition was combined with a sonication
      pretreatment. Sorption isotherm fitting indicated that the maximum sorption
      capacity, sorption affinity, and heterogeneity of the CNT surface were all
      affected by sonication and the presence of HA at a concentration as low as 1
      mg/L. The present results contribute to an improved understanding of the sorption
      behavior of CNTs in both natural and wastewater systems.

PMID- 22656043
TI  - Congestive hepatopathy and hypoxic hepatitis in heart failure: a cardiologist's
      point of view.
AB  - In the setting of long-standing severe chronic heart failure, other organ systems
      are also involved. The liver is one of the organs that are very sensitive to
      haemodynamic changes. Differential diagnosis of the liver injury is extremely
      important in the cardiologist's clinical practice and calls for cardiologist's
      and hepatologist's collaboration because there are many other diseases that can
      affect the liver and mimic haemodynamic injury. In this article, liver injuries
      depending on cardiocirculatory dysfunction such as hypoxic hepatitis and
      congestive hepatopathy are analysed. The material in the article is presented in
      two aspects: the evaluation and treatment of heart failure in order to prevent
      pathologic processes in the liver, and the recognition of the liver injury,
      including diagnostic tests which are essential for differential diagnosis of
      different liver pathologies.

PMID- 22656045
TI  - ST-elevation during surgery in a young male: who would bet on inverted takotsubo
      syndrome?

PMID- 22656044
TI  - Personalized antiplatelet treatment after percutaneous coronary intervention: the
      MADONNA study.
AB  - BACKGROUND AND OBJECTIVES: Clopidogrel non-responsiveness is associated with
      adverse clinical outcome. We aimed to investigate whether individualized
      antiplatelet treatment in clopidogrel non-responders is an effective and safe
      strategy. METHODS: This was a prospective non-randomized non-blinded study
      comparing two cohorts (guided and non-guided treatment) with a follow-up of 1
      month. Responsiveness to clopidogrel was assessed by multiple electrode
      aggregometry (MEA) in 798 patients with coronary artery disease undergoing
      percutaneous coronary intervention (PCI). In the guided group (n=403) clopidogrel
      non-responders received repeated loading doses of clopidogrel or prasugrel, in
      the non-guided group (n=395) clopidogrel non-responders did not undergo any
      change in treatment. RESULTS: Stent thrombosis occurred significantly less often
      in the guided group than in the non-guided group (0.2% vs. 1.9%; p=0.027). The
      multivariate Cox regression analysis showed that patients in the non-guided group
      were at a 7.9-fold higher risk to develop stent thrombosis compared to the guided
      group (OR: 7.9; 95% CI: 1.08-69.2; p=0.048). In line with this, acute coronary
      syndrome occurred significantly less often in the guided group than in the non
      guided group (0% vs. 2.5%; p=0.001) whereas there was no difference in the event
      rates of cardiac death (2% vs. 1.3%; p=0.422) or major bleedings (1% vs. 0.3%;
      p=0.186). CONCLUSION: Personalized antiplatelet treatment according to the
      platelet function testing with MEA resulted in an improved efficacy with an equal
      safety compared to the standard treatment.

PMID- 22656046
TI  - Alkaline phosphatase and arterial structure and function in hypertensive African
      men: the SABPA study.
AB  - BACKGROUND: Vascular calcification is believed to be due to the conversion of
      vascular smooth muscle cells into osteoblast-like cells and is associated with
      mortality. Since hypertension and related mortality in Africans is a concern, we
      investigated associations between a marker of osteoblastic activity, alkaline
      phosphatase (ALP), and measures of arterial structure and function in
      hypertensive African men. METHODS: This study included 79 participants. We
      conducted 24h ambulatory blood pressure and carotid intima-media thickness (cIMT)
      measurements. cIMT was obtained with an intra-observer variability of 0.04 mm and
      the cross-sectional wall area (CSWA) was calculated. ALP was measured in serum.
      RESULTS: ALP was within its reference range (101.6 vs. 30.0-120.0 U/L), however
      cIMT was higher when this group was stratified and compared to gender and age
      specific reference values. In univariate and partial regressions, and confirmed
      with multiple regression analyses, 24h systolic blood pressure (beta=0.289,
      p=0.018), 24h pulse pressure (beta=0.387, p=0.002), but not 24h diastolic blood
      pressure (beta=0.073, p=0.58), were positively associated with ALP. In addition,
      mean cIMT (beta=0.322, p=0.006) and CSWA (beta=0.285, p=0.013) also correlated
      positively with ALP after adjusting for significant covariates, and after
      excluding participants with diabetes, renal dysfunction or a HIV positive status.
      CONCLUSION: Serum alkaline phosphatase is adversely associated with measures of
      arterial structure and function in hypertensive African men.

PMID- 22656047
TI  - CB1 cannabinoid receptor deficiency promotes cardiac remodeling induced by
      pressure overload in mice.
AB  - BACKGROUND: The endocannabinoid system is known to play a role in regulating
      myocardial contractility, but the influence of cannabinoid receptor 1 (CB1)
      deficiency on chronic heart failure (CHF) remains unclear. In this study we
      attempted to investigate the effect of CB1 deficiency on CHF induced by pressure
      overload and the possible mechanisms involved. METHODS AND RESULTS: A CHF model
      was created by transverse aortic constriction (TAC) in both CB1 knockout mice and
      wild-type mice. CB1 knockout mice showed a marked increase of mortality due to
      CHF from 4 to 8 weeks after TAC (p=0.021). Five weeks after TAC, in contrast to
      wild-type mice, CB1 knockout mice had a higher left ventricular (LV) end
      diastolic pressure, lower rate of LV pressure change (+/- dp/dt max), lower LV
      contractility index, and a larger heart weight to body weight ratio and lung
      weight to body weight ratio compared with wild-type mice (all p<0.05-0.001).
      Phosphorylation of the epidermal growth factor receptor (EGFR) and mitogen
      activated protein kinases (P38 and ERK) was higher in CB1 knockout mice than that
      in wild-type mice. In cultured neonatal rat cardiomyocytes, a CB1 agonist reduced
      cAMP production stimulated by isoproterenol or forskolin, and suppressed
      phosphorylation of the EGFR, P38, and ERK, while the inhibitory effect of a CB1
      agonist on EGFR phosphorylation was abrogated by CB1 knockdown. CONCLUSION: These
      findings indicate that cannabinoid receptor 1 inactivation promotes cardiac
      remodeling by enhancing the activity of the epidermal growth factor receptor and
      mitogen-activated protein kinases.

PMID- 22656048
TI  - Serum 25-dihydroxyvitamin D levels correlate with CD4(+)Foxp3(+) T-cell numbers
      in moderate/severe asthma.

PMID- 22656049
TI  - Comparative kinetics of thiol oxidation in two distinct free-radical generating
      systems: SIN-1 versus AAPH.
AB  - To study oxidative stress in biological systems, chemical compounds capable of
      producing free radicals have been widely used. Here, we compared two free-radical
      generators, 3-morpholinosydnonimine (SIN-1) and 2,2'-azo-bis(2-amidinopropane)
      hydrochloride (AAPH), by measuring the thiol oxidation kinetics of various
      thiols. We found that SIN-1 is > 30 times potent in causing thiol oxidation than
      AAPH. Kinetic simulations revealed that in the SIN-1 system (0.1 mM), superoxide,
      nitrogen dioxide and carbonate radicals are the major reactive species which, in
      combination, induce ~50% of thiol molecules to undergo one-electron oxidation,
      thereby forming the thiyl radical which propagates further thiol oxidation by
      direct coupling with thiolates. Similarly, the alkyl peroxyl radical derived from
      AAPH (3 mM) initiates comparable extent of one-electron oxidation and formation
      of the thiyl radical. In conclusion, our study provides experimental and
      theoretical evidence that SIN-1 is mainly an one-electron oxidizing agent that
      can be functionally mimicked by AAPH.

PMID- 22656050
TI  - Enantioselective synthesis of imidazolines with quaternary stereocenters by
      organocatalytic reaction of N-(heteroarenesulfonyl)imines with isocyanoacetates.
AB  - An organocatalytic enantioselective Mannich-type reaction of isocyanoacetate with
      N-sulfonylimines catalyzed by chiral thioureas derived from quinine yielded 2
      imidazolines with high diastereo- and enantioselectivities (up to >99:1 dr. and
      96% ee). This reaction provided a convenient route to access various imidazolines
      and related alpha,beta-diamino acids having a quaternary carbon center in high
      enantiomeric purities.

PMID- 22656052
TI  - Right treatment; right patient; right time.

PMID- 22656053
TI  - Patient satisfaction with intranasal fentanyl for breakthrough pain.

PMID- 22656054
TI  - Pediatric palliative care and the medical home.

PMID- 22656055
TI  - Mapping children's palliative care around the world: an online survey of
      children's palliative care services and professionals' educational needs.
AB  - AIMS: To map children's palliative care (CPC) around the world and to and survey
      the learning needs of respondents. METHODS: The study reports on the responses to
      an online questionnaire given by people downloading the online version of the
      'Children's Palliative Care in Africa' textbook. RESULTS: 346 people responded
      (251 health professionals) from all continents but mostly from Africa, N America
      or Europe. Respondents worked in various types of health facilities, but in
      Africa over half were HIV/AIDS treatment centres. The average number of children
      per year seen ranged from 136 in Africa to 82 in Europe. The overall mean
      confidence scores across all CPC subject areas was 3.2/5. Confidence increased
      significantly with the degree respondents were exposed to caring for dying
      children in practice. Nurses were marginally the most confident group, but less
      confident than doctors in pain and symptom-control. N Americans were more
      confident than others in all subject areas except HIV/AIDS and spirituality,
      where Africans were more confident. Europeans were more confident than Africans
      in symptom control subject areas. Africans see the most children, but have the
      least confidence, and fewest resources. DISCUSSION: This is a descriptive
      uncontrolled study so any apparent differences between respondent sub-groups
      require further validation. The study provides insight into who is providing CPC
      across the world, and highlights the multi-disciplinary nature of CPC. It raises
      questions about how we can best support colleagues in resource-limited settings.
      It suggests further study is required into the nature of regional demand for CPC,
      the best places to resource and provide CPC, the nature of professionals'
      training needs, the most effective ways to train and deliver CPC care, the best
      ways for professionals to support each other, and effective ways to share
      resources and knowledge across the world.

PMID- 22656056
TI  - Palliative sedation in Germany: how much do we know? A prospective survey.
AB  - BACKGROUND: Little is known about the practice of palliative sedation (PS) in
      Germany. This paper presents an analysis of sedation-related data obtained from
      the German standardized core documentation system (HOPE) for palliative care
      patients. METHODS: HOPE was complemented by an optional module on ethical
      decision making (EDM) which was pretested in 2004, data was collected in 2005-6
      during the annual 3-month census. Data was analyzed descriptively from palliative
      care units (PCU - representative) and inpatient hospice (H - non-representative
      control group). Chi(2) test was used to test for differences between the reported
      data per item and year within one kind of setting (significance level p <= 0.05).
      Free-text entries were categorized inductively. RESULTS: Datasets were obtained
      for 1,944 patients (P) with EDM. PS was performed in 13.0/11.8% (2005/2006) P in
      palliative care units (PCU) and 25.5/22.9% in hospices (H). Main reasons for PS
      in PCU were dyspnea, pain, fear or anxiety, in H reasons were inconsistent, high
      prevalence of psychosocial reasons. Most PS in PCU and about half of the PS in H
      were intermittent. Sedated P were younger than non-sedated. Only 7 P received PS
      after asking for euthanasia. The most used medication was midazolam. CONCLUSIONS:
      This study reveals a first insight into the use and practice of PS in German PCU
      and H. For a more detailed systematic survey into the course of decision-making
      and procedures, a new complementary optional module on PS is being developed by
      the HOPE group.

PMID- 22656057
TI  - Asking about cultural beliefs in palliative care #216.

PMID- 22656058
TI  - Palliative care consultation in the ICU #253.
AB  - Specialist palliative care consultations, together with integration of palliative
      care principles into the care of all ICU patients, can improve the patient/family
      experience, reduce length of stay, improve ICU throughput without increasing
      mortality, and lower health care costs.

PMID- 22656059
TI  - Dilemma of a healthcare proxy.

PMID- 22656060
TI  - Physician assisted dying...if ever there were a case.

PMID- 22656064
TI  - Microfluidic flow cell for sequential digestion of immobilized proteoliposomes.
AB  - We have developed a microfluidic flow cell where stepwise enzymatic digestion is
      performed on immobilized proteoliposomes and the resulting cleaved peptides are
      analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The flow
      cell channels consist of two parallel gold surfaces mounted face to face with a
      thin spacer and feature an inlet and an outlet port. Proteoliposomes (50-150 nm
      in diameter) obtained from red blood cells (RBC), or Chinese hamster ovary (CHO)
      cells, were immobilized on the inside of the flow cell channel, thus forming a
      stationary phase of proteoliposomes. The rate of proteoliposome immobilization
      was determined using a quartz crystal microbalance with dissipation monitoring
      (QCM-D) which showed that 95% of the proteoliposomes bind within 5 min. The flow
      cell was found to bind a maximum of 1 MUg proteoliposomes/cm(2), and a minimum
      proteoliposome concentration required for saturation of the flow cell was
      determined to be 500 MUg/mL. Atomic force microscopy (AFM) studies showed an even
      distribution of immobilized proteoliposomes on the surface. The liquid
      encapsulated between the surfaces has a large surface-to-volume ratio, providing
      rapid material transfer rates between the liquid phase and the stationary phase.
      We characterized the hydrodynamic properties of the flow cell, and the force
      acting on the proteoliposomes during flow cell operation was estimated to be in
      the range of 0.1-1 pN, too small to cause any proteoliposome deformation or
      rupture. A sequential proteolytic protocol, repeatedly exposing proteoliposomes
      to a digestive enzyme, trypsin, was developed and compared with a single-digest
      protocol. The sequential protocol was found to detect ~65% more unique membrane
      associated protein (p < 0.001, n = 6) based on peptide analysis with LC-MS/MS,
      compared to a single-digest protocol. Thus, the flow cell described herein is a
      suitable tool for shotgun proteomics on proteoliposomes, enabling more detailed
      characterization of complex protein samples.

PMID- 22656065
TI  - Catalytic four-electron reduction of O2 via rate-determining proton-coupled
      electron transfer to a dinuclear cobalt-MU-1,2-peroxo complex.
AB  - Four-electron reduction of O(2) by octamethylferrocene (Me(8)Fc) occurs
      efficiently with a dinuclear cobalt-MU-1,2-peroxo complex, 1, in the presence of
      trifluoroacetic acid in acetonitrile. Kinetic investigations of the overall
      catalytic reaction and each step in the catalytic cycle showed that proton
      coupled electron transfer from Me(8)Fc to 1 is the rate-determining step in the
      catalytic cycle.

PMID- 22656066
TI  - Improved pyrogallol autoxidation method: a reliable and cheap superoxide
      scavenging assay suitable for all antioxidants.
AB  - The original pyrogallol (1,2,3-trihydroxybenzene) method, which was developed
      specifically for superoxide dismutase, is now widely used for measuring
      superoxide-scavenging of other antioxidants. However, the strong pH effect has
      been ignored. In this study, the influencing factors have been systematically
      investigated for the first time, and a number of experiments have proved that the
      pH is of major importance. As major antioxidants contain carboxylic acid, ester,
      or lactone groups, pH 8.2 should be modified to physiological pH 7.4. The
      improved procedure is as follows. A pyrogallol solution (in 1 M HCl) is
      thoroughly mixed with pH 7.4 Tris-HCl buffer; A(325 nm) is measured every 30 s
      for 5 min at 37  degrees C. As the DeltaA(325 nm, control) value reflects the
      initial concentration of substrate (*)O(2)(-), it should be well controlled to
      guarantee the accuracy of the method. The improved pyrogallol method is a
      reliable and cheap superoxide-scavenging assay suitable for all types of
      antioxidants.

PMID- 22656067
TI  - Characterization of beta-N-acetylhexosaminidase (LeHex20A), a member of glycoside
      hydrolase family 20, from Lentinula edodes (shiitake mushroom).
AB  - We purified and cloned a beta-N-acetylhexosaminidase, LeHex20A, with a molecular
      mass of 79 kDa from the fruiting body of Lentinula edodes (shiitake mushroom).
      The gene lehex20a gene had 1,659 nucleotides, encoding 553 amino acid residues.
      Sequence analysis indicated that LeHex20A belongs to glycoside hydrolase (GH)
      family 20, and homologues of lehex20a are broadly represented in the genomes of
      basidiomycetes. Purified LeHex20A hydrolyzed the terminal monosaccharide residues
      of beta-N-acetylgalactosaminides and beta-N-acetylglucosaminides, indicating that
      LeHex20A is a beta-N-acetylhexosaminidase classified into EC 3.2.1.52. The
      maximum LeHex20A activity was observed at pH 4.0 and 50 degrees C. The kinetic
      constants were estimated using chitooligosaccharides with degree of
      polymerization 2-6. GH20 beta-N-acetylhexosaminidases generally prefer chitobiose
      among natural substrates. However, LeHex20A had the highest catalytic efficiency
      (kcat/Km) for chitotetraose, and the Km values for GlcNAc6 were 3.9-fold lower
      than for chitobiose. Furthermore, the enzyme partially hydrolyzed amorphous
      chitin polymers. These results indicate that LeHex20A can produce N
      acetylglucosamine from long-chain chitomaterials.

PMID- 22656068
TI  - Molecular method for the characterization of Coxiella burnetii from clinical and
      environmental samples: variability of genotypes in Spain.
AB  - BACKGROUND: Coxiella burnetii is a highly clonal microorganism which is difficult
      to culture, requiring BSL3 conditions for its propagation. This leads to a scarce
      availability of isolates worldwide. On the other hand, published methods of
      characterization have delineated up to 8 different genomic groups and 36
      genotypes. However, all these methodologies, with the exception of one that
      exhibited limited discriminatory power (3 genotypes), rely on performing between
      10 and 20 PCR amplifications or sequencing long fragments of DNA, which make
      their direct application to clinical samples impracticable and leads to a scarce
      accessibility of data on the circulation of C. burnetii genotypes. RESULTS: To
      assess the variability of this organism in Spain, we have developed a novel
      method that consists of a multiplex (8 targets) PCR and hybridization with
      specific probes that reproduce the previous classification of this organism into
      8 genomic groups, and up to 16 genotypes. It allows for a direct characterization
      from clinical and environmental samples in a single run, which will help in the
      study of the different genotypes circulating in wild and domestic cycles as well
      as from sporadic human cases and outbreaks. The method has been validated with
      reference isolates. A high variability of C. burnetii has been found in Spain
      among 90 samples tested, detecting 10 different genotypes, being those adaA
      negative associated with acute Q fever cases presenting as fever of intermediate
      duration with liver involvement and with chronic cases. Genotypes infecting
      humans are also found in sheep, goats, rats, wild boar and ticks, and the only
      genotype found in cattle has never been found among our clinical samples.
      CONCLUSIONS: This newly developed methodology has permitted to demonstrate that
      C. burnetii is highly variable in Spain. With the data presented here, cattle
      seem not to participate in the transmission of C. burnetii to humans in the
      samples studied, while sheep, goats, wild boar, rats and ticks share genotypes
      with the human population.

PMID- 22656069
TI  - Transcatheter versus surgical treatment for aortic stenosis: patient selection
      and early outcome.
AB  - OBJECTIVES: To describe short-term clinical and echocardiography outcomes in
      patients undergoing transcatheter aortic valve implantation (TAVI) and surgical
      aortic valve replacement (SAVR). To explore patient selection criteria for
      treatment with TAVI. DESIGN: TAVI patients (n = 45) were matched to SAVR patients
      (n = 45) with respect to age within +/- 10 years, sex and systolic left
      ventricular function. RESULTS: TAVI patients were older, 82 +/- 8 versus 78 +/- 5
      years (p = 0.005) and they had higher logEuroSCORE, 16 +/- 11% versus 8 +/- 4% (p
      = 0.001). There were no significant differences in 30 days mortality, stroke and
      myocardial infarction. TAVI patients received less erythrocyte (53% vs. 78%, p =
      0.03) and thrombocyte (7% vs. 27%, p = 0.02) transfusions. Postoperative atrial
      fibrillation was less common (18% vs. 60%, p = 0.001) in the TAVI group.
      Paravalvular regurgitation was more common in TAVI patients (87% vs. 0%, p =
      0.001) and 27% had access site complications. Aortic transvalvular velocity was
      2.3 +/- 0.4 m/s versus 2.6 +/- 0.5 m/s (p = 0.002) and mean valve pressure
      gradient was 12 +/- 4 mmHg versus 15 +/- 5 mmHg (p = 0.01) in the TAVI and SAVR
      groups, respectively. Twenty-nine (64%) of the TAVI patients had logEuroSCORE =
      15%. CONCLUSIONS: Both TAVI and SAVR have good short term clinical outcome with
      excellent hemodynamic result. In clinical practice, factors other than high
      logEuroSCORE play an important role in patient selection for TAVI.

PMID- 22656070
TI  - An amide-linked chromophore-catalyst assembly for water oxidation.
AB  - The synthesis and analysis of a new amide-linked, dinuclear [Ru(bpy)(2)(bpy-ph-NH
      CO-trpy)Ru(bpy)(OH(2))](4+) (bpy = 2,2'-bipyridine; bpy-ph-NH-CO-trpy = 4
      (2,2':6',2"-terpyridin-4'-yl)-N-[(4'-methyl-2,2'-bipyridin-4-yl)methyl]benzamide)
      assembly that incorporates both a light-harvesting chromophore and a water
      oxidation catalyst are described. With the saturated methylene linker present,
      the individual properties of both the chromophore and catalyst are retained
      including water oxidation catalysis and relatively slow energy transfer from the
      chromophore excited state to the catalyst.

PMID- 22656071
TI  - Gel-based self-propelling particles get programmed to dance.
AB  - We present a class of gel-based self-propelling particles moving by the Marangoni
      effect in an oscillatory mode. The particles are made of an ethanol-infused
      polyacrylamide hydrogel contained in plastic tubing. These gel boats floating on
      the water surface exhibit periodic propulsion for several hours. The release of
      ethanol from the hydrogel takes place beneath the liquid surface. The released
      ethanol rises to the air-water interface by buoyancy and generates a self
      sustained cycle of surface tension gradient driven motion. The disruption of the
      ethanol flux to the surface by the bulk flows around the moving particle results
      in their pulsating motion. The pulse interval and the distance propelled in a
      pulse by these gel floaters were measured and approximated by simple expressions
      based on the rate of ethanol mass-transfer through and out of the hydrogel. This
      allowed us to design a multitude of particles performing periodic steps in
      different directions or at different angles of rotation, traveling in complex
      preprogrammed trajectories on the surface of the liquid. Similar gel-based self
      propelling floaters can find applications as mixers and cargo carriers in lab-on
      a-chip devices, and in various platforms for sensing and processing at the
      microscale.

PMID- 22656072
TI  - Summary of AHRQ's comparative effectiveness review of drug therapy for rheumatoid
      arthritis (RA) in adults--an update.
AB  - BACKGROUND: In 2011, the Agency for Health Care Research and Quality (AHRQ)
      published a systematic review on the comparative effectiveness of disease
      modifying anti-rheumatic drugs (DMARDs) used to treat adults with rheumatoid
      arthritis (RA). The publication was an update to a 2007 report. A total of 258
      published articles were used in the AHRQ review to compare the effectiveness of
      corticosteroids, and oral and biologic DMARDs in the treatment of RA. Head-to
      head studies and prospective cohort trials were used to compare one drug to
      another in determining efficacy and effectiveness. AHRQ compiled this report in
      an attempt to summarize and integrate the available data for clinicians to make
      evidence based practice decisions for their patients since there is limited
      consensus among the medical community regarding the comparative effectiveness of
      drugs used to treat RA. The report reveals there is still much research to be
      done concerning the side effects of these agents and their influence in different
      patient subgroups. OBJECTIVES: To: (a) utilize review findings to make diagnostic
      and treatment management decisions in clinical practice, (b) inform clinicians on
      the findings from the updated AHRQ's 2011 comparative effectiveness review on
      drug therapy for RA in adults, and (c) identify shortcomings in the current
      research and future directions revealed by the report. SUMMARY: Rheumatoid
      arthritis is a major public health burden. The 2011 updated AHRQ report includes
      several new medications approved by the FDA since 2007. The review includes 31
      head-to-head randomized clinical trials (RCTs), 1 head-to-head nonrandomized
      controlled trial, 44 placebo controlled trials, 28 meta-analyses or systematic
      reviews, and 107 observational studies. Most of the studies used for the
      comparative analysis are of fair quality with an insufficient to moderate
      strength of evidence assigned to the findings (Table 1). A mixed treatment
      comparisons (MTC)meta-analysis from the AHRQ report found that the biologic
      etanercept has a higher probability of improvement in disease activity compared
      with other biologic DMARDs, but the MTC findings have a low strength of evidence
      and caution is recommended in the interpretation of this weak evidence. For
      patients with early RA, limited evidence precludes conclusions about the
      superiority of one combination therapy versus another. The data are also
      inconclusive for comparisons of therapeutic similarity among oral DMARDs
      including the limitation created by differences inmethotrexate (MTX) dosing
      across trials. Extensive clinical experience over the years support the preferred
      use of MTX in most patients versus other oral DMARDs as well as its use in
      multidrug regimens, whereas there is little data on the use of oral DMARDs in
      combination with biologic agents. The review does not support a specific biologic
      DMARD over another due to the lack of head-to-head trials comparing these agents
      using validated RA outcome measures. The data show that the majority of biologics
      have approximately the same efficacy except for anakinra, which was found to be
      less effective. The biologic and oral DMARDs are similar in overall tolerability,
      but several studies suggest that adverse events are more common with biologic
      DMARDs versus oral DMARDs. Based on limited evidence, the oral DMARDs do not
      appear to have an increased risk of severe adverse events including
      cardiovascular events and cancer. Although most studies also found no increased
      risk of cardiovascular events or cancer with the biologic DMARDs, cohort studies
      show an increased risk of heart failure with adalimumab, etanercept, and
      infliximab compared with oral DMARDs. The updated AHRQ review synthesizes the
      current literature on therapies used for the treatment of RA in adults. The
      investigators are also able to identify pertinent research gaps in the literature
      that can be addressed with future research.

PMID- 22656073
TI  - Optimal utilization of modern reproductive technologies to maximize the gross
      margin of milk production.
AB  - In this study, a linear programming model was developed to maximize the gross
      margin of milk production by determining the optimal use of different
      reproductive technologies in a dairy herd. The model has the potential to vary
      the use of conventional artificial insemination, insemination with X-sorted
      sperm, and the use of unselected or sex-selected embryo recovery and transfer.
      Data from Finnish dairy herd recording systems were used to parameterize the
      model. This paper presents the results of 6 scenarios for a herd size of 60 dairy
      cows. In the basic scenario, the optimum economic combination for Finnish
      conditions was to inseminate 10 heifers and 22 cows with unsorted semen, 8
      heifers with X-sorted sperm, and to use 20 cows as embryo donors which was the
      upper constraint for this technique. The embryo donors were inseminated with
      conventional semen for both embryo production and their subsequent pregnancy.
      Without restriction on embryo recovery, the optimum combination was to use all
      heifers as donors of sex-selected embryos and all cows as donors of unselected
      embryos. It was more profitable to produce female embryos with X-sorted sperm
      than by sorting embryos. Embryo recipients were not economically justified in any
      scenario. In practice, the optimal strategy is herd-specific depending on the
      input costs, output values and the technical success of each reproductive
      technology in that herd. This single-year linear programming model adequately
      differentiates between breeding technologies within a herd, but further research
      is needed to develop dynamic models to consider genetic improvement and herd
      expansion.

PMID- 22656074
TI  - Effects of linguistic complexity and accommodations on estimates of ability for
      students with learning disabilities.
AB  - Many students with learning disabilities (SLD) participate in standardized
      assessments using test accommodations such as extended time, having the test
      items read aloud, or taking the test in a separate setting. Yet there are also
      aspects of the test items themselves, particularly the language demand, which may
      contribute to the effects of test accommodations. This study entailed an analysis
      of linguistic complexity (LC) and accommodation use for SLD in grade four on 2005
      National Assessment of Educational Progress (NAEP) reading and mathematics items.
      The purpose of this study was to investigate (a) the effects of test item LC on
      reading and mathematics item difficulties for SLD; (b) the impact of
      accommodations (presentation, response, setting, or timing) on estimates of
      student ability, after controlling for LC effects; and (c) the impact of
      differential facet functioning (DFF), a person-by-item-descriptor interaction, on
      estimates of student ability, after controlling for LC and accommodations'
      effects. For both reading and mathematics, the higher an item's LC, the more
      difficult it was for SLD. After controlling for differences due to
      accommodations, LC was not a significant predictor of mathematics items'
      difficulties, but it remained a significant predictor for reading items. There
      was no effect of accommodations on mathematics item performance, but for reading
      items, students who received presentation and setting accommodations scored lower
      than those who did not. No significant LC-by-accommodation interactions were
      found for either subject area, indicating that the effect of LC did not depend on
      the type of accommodation received.

PMID- 22656075
TI  - Preliminary evaluation of various training components on accuracy of Direct
      Behavior Ratings.
AB  - This study examined the impact of various components of rater training on the
      accuracy of rating behavior using Direct Behavior Rating-Single Item Scales (DBR
      SIS). Specifically, the addition of frame-of-reference and rater error training
      components to a standard package involving an overview and then modeling,
      practice, and feedback was investigated. In addition, amount of exposure to the
      direct training component (i.e., number of practice and feedback opportunities)
      was evaluated, and the rates at which behavior was displayed were carefully
      manipulated to control for and evaluate training impact by target and rate of
      behavior. The sample consisted of undergraduate students assigned to one of 6
      possible conditions. Overall findings suggested that completion of a training
      package did result in enhanced accuracy when using DBR-SIS to rate academic
      engagement and disruption. However, results also supported that the most
      comprehensive package of DBR training may not always result in greater
      improvements over a standard package involving direct training. In general, a
      more intensive training package appeared beneficial at improving ratings for
      targets that had previously been difficult to rate accurately (e.g., medium rate
      disruptive behavior). Limitations and implications for future research are
      discussed.

PMID- 22656076
TI  - Evaluating the generalization of math fact fluency gains across paper and
      computer performance modalities.
AB  - Computer-based interventions are being used more in the classroom. Student
      responses to these interventions often contribute to decisions making regarding
      important outcomes. It is important to understand the effect of these
      interventions within the context of the intervention as well as across related
      context. The current study examined the generalization of math fact fluency gains
      resulting from a computer-based intervention to paper-and-pencil performance. A
      total of 31 second grade students completed fluency drills on the computer or
      with paper and pencil. Pretest-posttest performance on both computer and paper
      and pencil for all students was evaluated using a doubly multivariate repeated
      measure ANOVA. Results indicated that gains achieved on the computer did not
      generalize to paper-and-pencil performance.

PMID- 22656077
TI  - Association of pupil vandalism, bullying and truancy with teachers' absence due
      to illness: a multilevel analysis.
AB  - The aim of this study was to examine whether vandalism, bullying, and truancy
      among pupils at school are associated with absence due to illness among teachers.
      Data on such problem behaviour of 17,033 pupils in 90 schools were linked to
      absence records of 2364 teachers. Pupil reported vandalism and bullying at the
      school-level were associated with teachers' short-term (1- to 3-day) absences.
      Cumulative exposure to various forms of pupils' problem behaviour was associated
      with even higher rates of short-term absences among teachers. No association was
      found between pupils' problem behaviour and teachers' long-term (>3-day)
      absences. In conclusion, there seems to be a link between pupils' problem
      behaviour and teachers' short-term absence due to illness. Further work should
      determine whether problem behaviour is a cause or a consequence of absences or
      whether the association is noncausal.

PMID- 22656078
TI  - Are boys better off with male and girls with female teachers? A multilevel
      investigation of measurement invariance and gender match in teacher-student
      relationship quality.
AB  - Although research consistently points to poorer teacher-student relationships for
      boys than girls, there are no studies that take into account the effects of
      teacher gender and control for possible measurement non-invariance across student
      and teacher gender. This study addressed both issues. The sample included 649
      primary school teachers (182 men) and 1493 students (685 boys). Teachers
      completed a slightly adapted version of the Student-Teacher Relationship Scale.
      The results indicated limited measurement non-invariance in teacher reports.
      Female teachers reported better (i.e., more close, less conflictual, and less
      dependent) relationships with students than male teachers. In addition, both male
      and female teachers reported more conflictual relationships with boys than with
      girls, and female teachers also reported less close relationships with boys than
      with girls. The findings challenge society's presumption that male teachers have
      better relationships with boys than women teachers.

PMID- 22656079
TI  - Preschool children's development in classic Montessori, supplemented Montessori,
      and conventional programs.
AB  - Research on the outcomes of Montessori education is scarce and results are
      inconsistent. One possible reason for the inconsistency is variations in
      Montessori implementation fidelity. To test whether outcomes vary according to
      implementation fidelity, we examined preschool children enrolled in high fidelity
      classic Montessori programs, lower fidelity Montessori programs that supplemented
      the program with conventional school activities, and, for comparison,
      conventional programs. Children were tested at the start and end of the school
      year on a range of social and academic skills. Although they performed no better
      in the fall, children in Classic Montessori programs, as compared with children
      in Supplemented Montessori and Conventional programs, showed significantly
      greater school-year gains on outcome measures of executive function, reading,
      math, vocabulary, and social problem-solving, suggesting that high fidelity
      Montessori implementation is associated with better outcomes than lower fidelity
      Montessori programs or conventional programs.

PMID- 22656080
TI  - The impact of baseline trend control on visual analysis of single-case data.
AB  - The impact of baseline trend control on visual analyses of AB intervention graphs
      was examined with simulated data at various values of baseline trend,
      autocorrelation, and effect size. Participants included 202 undergraduate
      students with minimal training in visual analysis and 10 graduate students and
      faculty with more training and experience in visual analysis. In general, results
      were similar across both groups of participants. Without statistical adjustments
      to correct for baseline trend, Type I errors greatly increased as baseline trend
      increased. With corrections for baseline trend, fewer Type I errors were made. As
      trend increased, participants made fewer Type II errors on the unadjusted graphs
      as compared to the graphs with baseline trend control. The greater Type II error
      rate on adjusted graphs could be an artifact of study design (i.e., participants
      did not know if baseline trend control had been applied), and the impact of MASAJ
      on Type II errors needs to be explored in detail prior to more widespread use of
      the method. Implications for future use of baseline trend control techniques by
      educational professionals are discussed.

PMID- 22656081
TI  - Cystic changes in desmoplastic fibroma of bone: a new MRI finding.
AB  - AIM: To evaluate the magnetic resonance imaging features of desmoplastic fibroma
      (DF) of bone. MATERIALS AND METHODS: Two radiologists retrospectively evaluated
      imaging findings of pathologically confirmed DFs in eight patients. Involved
      sites and longitudinal location in long bones were evaluated using radiography
      and computed tomography (CT). At MRI, the presence of low signal areas on T2
      weighted images (low-T2), enhancement, cystic changes, and locations of the mass
      were evaluated. The location of masses was evaluated, based on cortical
      disruption and adjacent soft-tissue extension. RESULTS: Involved sites were the
      femur in three patients, the tibia in two, and the humerus, fibula, and pubic
      bone in one each. Of the seven masses in the long bones, three were located in
      the epi- and metaphysis, two in the meta- and diaphysis, one in the diaphysis,
      and one in the epiphysis. Seven masses had areas of low T2-weighted or
      heterogeneous enhancement, and three (38%) showed cystic changes. cortical
      disruption was seen at MRI in six of eight patients (88%). CONCLUSION: DFs
      contained cystic change. Cortical disruption may also occur, which may cause
      confusion with malignant lesions.

PMID- 22656082
TI  - Modified anteroposterior and oblique radiographs of the midfoot and their
      efficiency in demonstrating the tarsometatarsal joints.
AB  - AIM: To assess whether conventional and modified anteroposterior and oblique
      radiographs of the midfoot can be used to demonstrate tarsometatarsal (TMT)
      joints clearly. MATERIALS AND METHODS: Conventional anteroposterior and oblique
      radiographs of the midfoot were taken of 152 volunteers. Modified radiographs of
      the midfoot were taken of 14 volunteers by tilting the radiographic system tube
      and placing volunteers' feet on different footboards. Both conventional and
      modified radiographs were taken of 27 patients with midfoot injuries to
      demonstrate the injuries to the TMT joints. Two radiologists assessed the
      radiological demonstration of the TMT joints. Statistical analyses were performed
      using SPSS 13.0 for Windows. RESULTS: Conventional radiographs of the midfoot did
      not sufficiently clearly demonstrate TMT joints. They could not demonstrate the
      majority of the TMT joints. The modified anteroposterior radiographs of the
      midfoot taken with the radiographic system tube tilted 30 degrees  towards the
      calcaneus demonstrated most TMT joints clearly. The modified oblique radiographs
      taken with the foot placed on a 30 degrees  footboard and with the radiographic
      system tube tilted 20 degrees  towards the calcaneus also showed the majority of
      TMT joints clearly. For the evaluation of midfoot injuries, modified radiographs
      perform better than conventional radiographs. CONCLUSIONS: Modified
      anteroposterior and oblique radiographs, which allow clear detection of the
      articulation and trabeculae of TMT joints, are valuable alternatives when
      assessing TMT joints.

PMID- 22656086
TI  - Compartmentalization of electrophoretically separated analytes in a multiphase
      microfluidic platform.
AB  - Herein, we describe the monolithic integration of a multiphase microfluidic
      system to a microcapillary gel electrophoresis (MUCGE) architecture for the
      complete isolation and storage of separated analyte bands. Within this platform,
      analyte molecules are separated using microchannel gel electrophoresis, and the
      eluted bands are stored in a sequence of approximately 40-600 encapsulating
      microdroplets. Importantly, employing such a system allows for total control of
      droplet size, shape, and composition. This approach is utilized to separate,
      optically detect, and encapsulate two fluorescent analytes from a composite
      sample mixture. Further to this, we subsequently investigate the potential of the
      system to be used as a concentration gradient generator through analysis of the
      segmented analyte bands and droplet composition.

PMID- 22656088
TI  - Wiley-interscience.

PMID- 22656087
TI  - Ert.

PMID- 22656090
TI  - Trace-metal adsorption characteristics.

PMID- 22656091
TI  - Letters.

PMID- 22656092
TI  - Rush me your free catalog!

PMID- 22656094
TI  - Martek instruments, inc.

PMID- 22656093
TI  - Fear of hazardous wastes: a self-fulfilling prophecy?

PMID- 22656096
TI  - Washington.

PMID- 22656095
TI  - International.

PMID- 22656097
TI  - States.

PMID- 22656098
TI  - Science.

PMID- 22656099
TI  - Technology.

PMID- 22656100
TI  - Industry.

PMID- 22656101
TI  - Trying to track down a.chemistry professor?

PMID- 22656102
TI  - Formaldehyde.

PMID- 22656103
TI  - Supercritical fluids.

PMID- 22656104
TI  - To order american chemical society.

PMID- 22656105
TI  - A compensation fund for hazardous waste injuries.

PMID- 22656106
TI  - Health effects of drinking water disinfectants and disinfectant by-products.

PMID- 22656107
TI  - Mutagenicity testing in environmental toxicology.

PMID- 22656108
TI  - Products.

PMID- 22656109
TI  - Analytical products group, inc.

PMID- 22656111
TI  - Isco.

PMID- 22656110
TI  - Literature.

PMID- 22656114
TI  - Biomass as a nonfossil fuel source.

PMID- 22656113
TI  - Beckman.

PMID- 22656115
TI  - Foxboro.

PMID- 22656116
TI  - Courses.

PMID- 22656117
TI  - This publication is available Microform.

PMID- 22656120
TI  - Consulting services.

PMID- 22656118
TI  - International.

PMID- 22656122
TI  - Index to the advertisers in this issue.

PMID- 22656121
TI  - Advirtisement/Classified.

PMID- 22656123
TI  - Classified.

PMID- 22656124
TI  - Written by leading authorities at.

PMID- 22656125
TI  - Melatonin attenuated mediators of neuroinflammation and alpha-7 nicotinic
      acetylcholine receptor mRNA expression in lipopolysaccharide (LPS) stimulated rat
      astrocytoma cells, C6.
AB  - Melatonin has been known to affect a variety of astrocytes functions in many
      neurological disorders but its mechanism of action on neuroinflammatory cascade
      and alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) expression are still
      not properly understood. Present study demonstrated that treatment of C6 cells
      with melatonin for 24 hours significantly decreased lipopolysaccharide (LPS)
      induced nitrative and oxidative stress, expressions of cyclooxigenase-2 (COX-2),
      inducible nitric-oxide synthase (iNOS) and glial fibrillary acidic protein
      (GFAP). Melatonin also modulated LPS-induced mRNA expressions of alpha7-nAChR and
      inflammatory cytokine genes. Furthermore, melatonin reversed LPS-induced changes
      in C/EBP homologous protein 10 (CHOP), microsomal prostaglandin E synthase
      1(mPGES-1) and phosphorylated p38 mitogen activated protein kinase (P-p38).
      Treatment with pyrrolidine dithiocarbamate (PDTC) inhibited alpha7-nAChR mRNA
      expression in LPS-induced C6 cells. Our findings explored anti-neuroinflammatory
      action of melatonin, which may suggests its beneficial roles in the
      neuroinflammation associated disorders.

PMID- 22656126
TI  - Determination of chlorophylls in Taraxacum formosanum by high-performance liquid
      chromatography-diode array detection-mass spectrometry and preparation by column
      chromatography.
AB  - Taraxacum formosanum, a well-known Chinese herb shown to be protective against
      hepatic cancer as well as liver and lung damage, may be attributed to the
      presence of abundant carotenoids and chlorophylls. However, the variety and
      content of chlorophylls remain uncertain. The objectives of this study were to
      develop an high-performance liquid chromatography-diode array detection-mass
      spectrometry method for determination of chlorophylls in T. formosanum and
      preparation by column chromatography. An HyPURITY C18 column and a gradient
      mobile phase of water (A), methanol (B), acetonitrile (C), and acetone (D) could
      resolve 10 chlorophylls and an internal standard Fast Green FCF within 30 min
      with a flow rate at 1 mL/min and detection at 660 nm. Both chlorophylls a and a'
      were present in the largest amount (1389.6 MUg/g), followed by chlorophylls b and
      b' (561.2 MUg/g), pheophytins a and a' (31.7 MUg/g), hydroxychlorophyll b (26.5
      MUg/g), hydroxychlorophylls a and a' (9.8 MUg/g), and chlorophyllides a and a'
      (0.35 MUg/g). A glass column containing 52 g of magnesium oxide-diatomaceous
      earth (1:3, w/w) could elute chlorophylls with 800 mL of acetone containing 50%
      ethanol at a flow rate of 10 mL/min. Some new chlorophyll derivatives including
      chlorophyllide b, pyropheophorbide b, hydroxypheophytin a, and hydroxypheophytin
      a' were generated during column chromatography but accompanied by a 63% loss in
      total chlorophylls. Thus, the possibility of chlorophyll fraction prepared from
      T. formosanum as a raw material for future production of functional food needs
      further investigation.

PMID- 22656181
TI  - Combination of bioinspiration: a general route to superhydrophobic particles.
AB  - We combine two amazing abilities found in nature: the superhydrophobic property
      of lotus leaf and the adhesive ability of mussel adhesive protein. The molecular
      structure mimic of the single units of adhesive proteins, dopamine, was
      polymerized in an alkaline aqueous solution to encapsulate microparticles. The as
      formed thin polydopamine walls worked as reactive templates to generate silver
      nanoparticles on the capsuled particles. As a result, core/shell/satellite
      composite particles were generated with a hierarchical structure similar to the
      micromorphology of lotus leaf. The composite particles exhibited extremely water
      repellence after fluorination. Because dopamine can deposit and adhere to all
      kinds of materials, this method can be applied to diverse microparticles, from
      organic to inorganic. In addition, particles of different sizes and matters can
      be modified to superhydrophobic particles in one pot. Magnetic particles have
      also been prepared which could be used as oil-absorbent and magnetic controlled
      carriers. "Oil marbles" formed underwater were achieved for the first time.

PMID- 22656182
TI  - Conduction block and axonal degeneration co-occurring in a patient with axonal
      Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome can present as demyelinating or axonal subtypes. Recent
      studies suggest that the neurophysiology of the axonal subtype not only exhibits
      axonal degeneration but can also show reversible conduction failure at the early
      stages. It is less certain if reversible conduction failure is evident in only a
      minority of patients with a specific subtype associated with better prognosis. We
      describe a 73-year-old man with Guillain-Barre syndrome and electrodiagnostic
      features of both reversible conduction block and possible axonal degeneration.
      Initial features of conduction failure were seen in both median nerves. This was
      followed by features of axonal degeneration, with corresponding weakness in the
      left abductor pollicis brevis and lumbricalis muscles, which are innervated by
      the median nerve, but rapid resolution of conduction block with corresponding
      rapid clinical recovery in the right. The presence of both features in a single
      patient provides further evidence that early conduction failure can be followed
      by either rapid resolution or axonal degeneration in the electrophysiological
      spectrum of axonal Guillain-Barre syndrome.

PMID- 22656183
TI  - Multiple microembolic brain infarctions in Clonorchis sinensis infestation.
AB  - We report a case of multiple cerebral infarctions as the first symptom of
      hypereosinophilia with Clonorchis sinensis infestation. The patient showed
      hypereosinophilia and elevated cardiac enzyme, and the egg test of C. sinensis
      was positive. CT scans of the chest and the abdomen revealed eosinophilic
      infiltration in both lung and liver. Over a period of six weeks after
      praziquantel medication, he recovered. C. sinensis infestation which is endemic
      in East Asian countries should be considered as a cause of multiple microembolic
      stroke associated with idiopathic hypereosinophilic syndrome.

PMID- 22656184
TI  - Musculoskeletal problems as an initial manifestation of Parkinson's disease: a
      retrospective study.
AB  - OBJECTIVE: The purpose of this study was to review the prevalence of
      musculoskeletal pain in the prodromal phase of PD, before the PD diagnosis is
      made. METHODS: A retrospective review of 82 PD patients was performed. Hospital
      inpatient notes and outpatient clinic admission notes were reviewed. The initial
      complaints prompting patients to seek medical attention were noted, as were the
      initial diagnoses. The symptoms were considered retrospectively to be associated
      with PD. RESULTS: Musculoskeletal pain was present as a prodromal PD symptom in
      27 (33%) cases initially diagnosed with osteoarthritis, degenerative spinal
      disease, and frozen shoulder. The mean time from the initial symptom appearance
      to dopaminergic treatment was 6.6 years in the musculoskeletal pain group and 2.3
      years in the group with typical PD signs. Significant improvement of
      musculoskeletal pain after the initiation of dopaminergic treatment was present
      in 23 (85%) cases. CONCLUSIONS: Of the PD patients who went on to develop motor
      features of PD, one third manifested musculoskeletal pain as the initial symptom.
      A good response to L-DOPA therapy was seen in 85% of cases presenting with
      musculoskeletal pain. Our findings suggest that musculoskeletal pain may be a
      significant feature in earlier PD stages.

PMID- 22656186
TI  - The burden of allergic rhinitis (AR) in Canada: perspectives of physicians and
      patients.
AB  - BACKGROUND: Allergic rhinitis (AR) is a common problem and we sought to examine
      the burden of disease and its management in Canada from the perspectives of
      patients and physicians. METHODS: Two parallel, Canadawide structured telephone
      interviews surveyed 1,001 AR patients and 160 physicians in July 2006. RESULTS:
      44% of patients had experienced nasal symptoms unrelated to a cold and 20% had a
      physician diagnosis of AR. At screening 27% reported asthma, 15% chronic or
      recurrent sinusitis and 5% nasal polyps. With attacks nasal congestion and runny
      nose were the most bothersome symptoms. Other problems experienced were fatigue
      (46%), poor concentration (32%), and reduced productivity (23%). Most (77%) had
      not seen a physician in the past year. Physicians estimated they prescribed
      intranasal cortico steroids (INCS) to most AR patients (77%) consistent with
      guidelines but only 19% of patients had used one in the last month. Only 48% of
      patients were very satisfied with their current INCS. 41% of AR patients reported
      discontinuing their INCS with the most common reason being a perceived lack of
      long-lasting symptom relief (44%). 52% of patients felt that their current INCS
      lost effectiveness over 24 h. The most common INCS side effects included dripping
      down the throat, bad taste, and dryness. Most AR patients reported lifestyle
      limitations despite treatment (66%). 61% of patients felt that their symptoms
      were only somewhat controlled or poorly/not controlled during their worst month
      in the past year. CONCLUSIONS: AR symptoms are common and many patients
      experience inadequate control. Physicians report they commonly prescribe
      intranasal corticosteroids, but patient's perceived loss of efficacy and side
      effects lead to their discontinuation. Persistent relief of allergic rhinitis
      symptoms remains a major unmet need. Better treatments and education are
      required.

PMID- 22656185
TI  - Upregulation of tumor necrosis factor receptor-associated factor 6 correlated
      with synovitis severity in rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease leading
      to joint destruction and disability. Focal bone erosion is due to excess bone
      resorption of osteoclasts. Tumor necrosis factor receptor-associated factor 6
      (TRAF6) is one of the critical mediators both in inflammatory signal pathway and
      differentiation and resorption activity of osteoclasts. Here we aimed to
      investigate TRAF6 expression in RA synovium and its correlation with histological
      synovitis severity and radiological joint destruction in RA. METHODS: Synovitis
      score was determined in needle biopsied synovium from 44 patients with active RA.
      Synovium from nine patients with osteoarthritis (OA) and seven with orthopedic
      arthropathies (Orth.A) were enrolled as "less inflamed" disease controls. Serial
      sections were stained immunohistochemically for TRAF6 as well as CD68
      (macrophage), CD3 (T cell), CD20 (B cell), CD38 (plasmocyte), CD79a (B lineage
      cells from pre-B cell to plasmocyte stage), and CD34 (endothelial cell). Double
      immunofluorescence staining of TRAF6 and CD68 were tested. Densities of positive
      staining cells were determined and correlated with histological disease activity
      (synovitis score) and radiographic joint destruction (Sharp score). RESULTS:
      TRAF6 expression was found in the intimal and subintimal area of RA synovium,
      with intense staining found in the endochylema and nucleus of intimal
      synoviocytes and subintimal inflammatory cells. Double immunofluorescence
      staining showed TRAF6 was expressed in most of the intimal cells and obviously
      expressed in CD68+ cells and some other CD68- cells in subintimal area. Synovial
      TRAF6 was significantly over-expressed in the RA group compared with the OA and
      Orth.A group (2.53 +/- 0.94 vs. 0.72 +/- 0.44 and 0.71 +/- 0.49, P < 0.0001).
      Synovial TRAF6 expression in RA correlated significantly with synovitis score (r
      = 0.412, P = 0.006), as well as the inflammatory cell infiltration (r = 0.367, P
      = 0.014). Significant correlation was detected between synovial TRAF6 expression
      and intimal CD68+ cells, as well as the cell density of subintimal CD68+ cells,
      CD3+ cells, CD20+ cells, CD38+ cells, and CD79a+ cells (all P < 0.05).
      CONCLUSIONS: Elevated synovial TRAF6 expression correlated with synovitis
      severity and CD68+ cell density in RA. It is, therefore, hypothesized that
      synovial TRAF6 is involved in the pathogenesis of synovial inflammation and
      osteoclast differentiation in RA.

PMID- 22656187
TI  - Pulmonary nocardiosis in patients with COPD: characteristics and prognostic
      factors.
AB  - INTRODUCTION: Pulmonary nocardiosis (PN) is a severe infection with a high
      morbidity and mortality that mainly affects immunocompromised patients. In recent
      years, an increase in PN cases has been detected among patients with chronic
      obstructive pulmonary disease (COPD). The factors that are associated with its
      presence and determine its prognosis remain unknown. METHODS: Retrospective study
      of COPD patients diagnosed with PN over the period from 1997-2009 at the Hospital
      de la Santa Creu i Sant Pau, in Barcelona (Spain). Demographic, clinical,
      microbiological and evolution data were evaluated in all cases RESULTS: Thirty
      patients were identified with PN and COPD. Mean age (standard deviation) was 76
      (7) years and the mean FEV(1) was 40 (14)%. Chronic respiratory failure was
      observed in 56,7% patients and 51,7% had received systemic corticosteroid therapy
      previous to the PN diagnosis. The most common symptoms were cough and dyspnea
      (90%). Alveolar infiltrates were observed in 60% of the cases. The most
      frequently isolated Nocardia species was N. cyriacigeorgica (68%). The one-month
      mortality rate was 17%, while the one-year mortality rate was 33%. The factors
      associated with mortality within the first year included previous systemic
      corticosteroid treatment, less than three months of specific antibiotic therapy
      and active associated neoplasm. CONCLUSIONS: PN affects patients with moderate
      severe COPD and has high short- and mid-term mortality rates. Previous
      corticosteroid treatment, specific antibiotic therapy for less than 3 months and
      active neoplasia were factors associated with mortality.

PMID- 22656189
TI  - Effect of Han-uvulopalatopharyngoplasty on flow-mediated dilatation in patients
      with moderate or severe obstructive sleep apnea syndrome.
AB  - CONCLUSION: Flow-mediated dilatation (FMD) is decreased in patients with moderate
      or severe obstructive sleep apnea syndrome (OSAS), and Han
      uvulopalatopharyngoplasty (H-UPPP) can improve FMD. OBJECTIVE: To evaluate FMD in
      patients with moderate or severe OSAS and observe the effect of H-UPPP on FMD in
      these patients. METHODS: Forty-nine patients who were first diagnosed with
      moderate or severe OSAS by polysomnography (PSG) and had no other diseases served
      as the experimental group, and 35 individuals with normal PSG as the control
      group. FMD was measured with high-resolution B-mode ultrasonography in the two
      groups. PSG and FMD were again performed in the experimental group 6 months after
      H-UPPP. RESULTS: FMD was significantly lower in the experimental group than in
      the control group (6.5 +/- 2.1% vs 11.2 +/- 2.9%, p < 0.01). FMD was
      significantly improved 6 months after H-UPPP compared with preoperative FMD (9.7
      +/- 2.7% vs 6.5 +/- 2.1%, p < 0.01).

PMID- 22656188
TI  - A systematic review of interventions in primary care to improve health literacy
      for chronic disease behavioral risk factors.
AB  - BACKGROUND: To evaluate the effectiveness of interventions used in primary care
      to improve health literacy for change in smoking, nutrition, alcohol, physical
      activity and weight (SNAPW). METHODS: A systematic review of intervention studies
      that included outcomes for health literacy and SNAPW behavioral risk behaviors
      implemented in primary care settings.We searched the Cochrane Library, Johanna
      Briggs Institute, Medline, Embase, CINAHL, Psychinfo, Web of Science, Scopus,
      APAIS, Australasian Medical Index, Google Scholar, Community of Science and four
      targeted journals (Patient Education and Counseling, Health Education and
      Behaviour, American Journal of Preventive Medicine and Preventive Medicine).Study
      inclusion criteria: Adults over 18 years; undertaken in a primary care setting
      within an Organisation for Economic Co-operation and Development (OECD) country;
      interventions with at least one measure of health literacy and promoting positive
      change in smoking, nutrition, alcohol, physical activity and/or weight; measure
      at least one outcome associated with health literacy and report a SNAPW outcome;
      and experimental and quasi-experimental studies, cohort, observational and
      controlled and non-controlled before and after studies.Papers were assessed and
      screened by two researchers (JT, AW) and uncertain or excluded studies were
      reviewed by a third researcher (MH). Data were extracted from the included
      studies by two researchers (JT, AW). Effectiveness studies were quality assessed.
      A typology of interventions was thematically derived from the studies by grouping
      the SNAPW interventions into six broad categories: individual motivational
      interviewing and counseling; group education; multiple interventions (combination
      of interventions); written materials; telephone coaching or counseling; and
      computer or web based interventions. Interventions were classified by intensity
      of contact with the subjects (High >= 8 points of contact/hours; Moderate >3 and
      <8; Low <= 3 points of contact hours) and setting (primary health, community or
      other).Studies were analyzed by intervention category and whether significant
      positive changes in SNAPW and health literacy outcomes were reported. RESULTS: 52
      studies were included. Many different intervention types and settings were
      associated with change in health literacy (73% of all studies) and change in
      SNAPW (75% of studies). More low intensity interventions reported significant
      positive outcomes for SNAPW (43% of studies) compared with high intensity
      interventions (33% of studies). More interventions in primary health care than
      the community were effective in supporting smoking cessation whereas the reverse
      was true for diet and physical activity interventions. CONCLUSION: Group and
      individual interventions of varying intensity in primary health care and
      community settings are useful in supporting sustained change in health literacy
      for change in behavioral risk factors. Certain aspects of risk behavior may be
      better handled in clinical settings while others more effectively in the
      community. Our findings have implications for the design of programs.

PMID- 22656190
TI  - Assessment of granulation technologies for an API with poor physical properties.
AB  - Granulation technologies are widely used in solid oral dosage forms to improve
      the physical properties during manufacture. Wet, dry, and melt granulation
      techniques were assessed for Compound A, a BCS class II compound.
      Characterization techniques were used to quantify physical property limitations
      inherent for Compound A including hygroscopicity, low solubility and bulk
      density, and poor powder flowability. High shear aqueous wet granulation induced
      an undesirable water mediated phase transition of the solid form. A formulation
      and process for dry granulation by roller compaction was developed and scaled to
      10 kg batch size. Roll force, and roll gap parameters were assessed. Porosity of
      compacted ribbons was analyzed by mercury intrusion porosimetry, and particle
      size distributions of milled ribbons by sieve analysis. A roll force of 15 kN/cm
      produced granules with higher density and improved flow properties compared to
      the pre-blend. Fines content (<75 um) decreased from approximately 90% pre
      granulation to 26% post-granulation. Cohesive properties of Compound A limited
      drug loading (API:excipient ratio) in roller compaction to 0.6:1 or less. Hot
      melt granulation by extrusion assessed with four polymers. A vast improvement in
      drug loading of 4:1 was achieved via melt processes using low molecular weight
      thermo-binders (glyceryl behenate and Polyethylene glycol 4000). Granules
      produced by melt processing contained less fines compared to wet and dry
      granulation. Both roller compaction and melt extrusion are viable granulation
      process alternatives for scale up to overcome the physical property limitations
      of Compound A.

PMID- 22656191
TI  - Development of multilocus putatively neutral DNA markers in the X-chromosome for
      population genetic studies in humans.
AB  - BACKGROUND: It has now been well documented that the type (coding, non-coding)
      and location (nuclear, mitochondrial etc.) of genetic markers heavily influence
      evolutionary inferences; realistic assumptions can be drawn if multiple
      putatively neutral DNA fragments spread across the genome are used. AIM: To infer
      human population history, Single Nucleotide Polymorphisms (SNPs), located in the
      non-coding regions of different genes in the X-chromosome have been developed as
      'putatively neutral markers'. SUBJECTS AND METHODS: A population sample
      consisting of 16 male individuals from the western part of India was utilized for
      sequencing eight DNA fragments located in introns of three genes (Duchenne
      muscular dystrophy, Factor IX and Pyruvate dehydrogenase E1 sub-unit) on the
      human X-chromosome. PCR amplification and DNA sequencing confirmed the
      polymorphic status of all the fragments. RESULTS: Twenty nine SNPs were found to
      be segregating in the Western Indian population samples. Using these SNPs the
      nucleotide diversity and demographic parameters of the Western Indian population
      were estimated. Several tests of neutrality ascertained that all eight fragments
      evolve putatively neutrally. Further, linkage disequilibrium analyses confirmed
      this fact. CONCLUSION: All eight DNA fragments seem to bear the characteristics
      to be considered as 'putatively neutral genetic markers' and thus, could be
      utilized for inference of human population and demographic histories.

PMID- 22656192
TI  - Criteria for robustness of heteroclinic cycles in neural microcircuits.
AB  - We introduce a test for robustness of heteroclinic cycles that appear in neural
      microcircuits modeled as coupled dynamical cells. Robust heteroclinic cycles
      (RHCs) can appear as robust attractors in Lotka-Volterra-type winnerless
      competition (WLC) models as well as in more general coupled and/or symmetric
      systems. It has been previously suggested that RHCs may be relevant to a range of
      neural activities, from encoding and binding to spatio-temporal sequence
      generation.The robustness or otherwise of such cycles depends both on the
      coupling structure and the internal structure of the neurons. We verify that
      robust heteroclinic cycles can appear in systems of three identical cells, but
      only if we require perturbations to preserve some invariant subspaces for the
      individual cells. On the other hand, heteroclinic attractors can appear robustly
      in systems of four or more identical cells for some symmetric coupling patterns,
      without restriction on the internal dynamics of the cells.

PMID- 22656193
TI  - Perovskite-to-postperovskite transitions in NaNiF3 and NaCoF3 and
      disproportionation of NaCoF3 postperovskite under high pressure and high
      temperature.
AB  - High-pressure structural phase transitions in NaNiF(3) and NaCoF(3) were
      investigated by conducting in situ synchrotron powder X-ray diffraction
      experiments using a diamond anvil cell. The perovskite phases (GdFeO(3) type)
      started to transform into postperovskite phases (CaIrO(3) type) at about 11-14
      GPa, even at room temperature. The transition pressure is much lower than those
      of oxide perovskites. The anisotropic compression behavior led to heavily tilted
      octahedra that triggered the transition. Unlike oxide postperovskites,
      fluoropostperovskites remained after decompression to 1 atm. The postperovskite
      phase in NaCoF(3) broke down into a mixture of unknown phases after laser heating
      above 26 GPa, and the phases changed into amorphous ones when the pressure was
      released. High-pressure and high-temperature experiments using a multianvil
      apparatus were also conducted to elucidate the phase relations in NaCoF(3).
      Elemental analysis of the recovered amorphous samples indicated that the NaCoF(3)
      postperovskite disproportionated into two phases. This kind of disproportionation
      was not evident in NaNiF(3) even after laser heating at 54 GPa. In contrast to
      the single postpostperovskite phase reported in NaMgF(3), such a
      postpostperovskite phase was not found in the present compounds.

PMID- 22656194
TI  - Multianalyte digital enzyme biosensors with built-in Boolean logic.
AB  - Novel biosensors based on the biocomputing concept digitally process multiple
      biochemical signals through Boolean logic networks of coupled biomolecular
      reactions and produce output in the form of a YES/NO response. Compared to
      traditional single-analyte sensing devices, biocomputing approach enables a high
      fidelity multianalyte biosensing, particularly beneficial for biomedical
      applications.

PMID- 22656195
TI  - Macrocompression and nanoindentation of soft viscoelastic biological materials.
AB  - The study of the mechanical behavior of soft biological materials presents many
      challenges due to the materials' time-dependent mechanical response as well as
      inherent size and shape limitations. In this study, by using agar as a surrogate
      material for soft tissues, the effects of these limitations upon standardized
      macroscale dynamic compression protocols are compared to dynamic nanoindentation
      procedures. Both techniques are then applied to dynamically test porcine sclera
      tissue, showing a significant difference in recorded loss and storage modulus
      values between the two methodologies. Additionally, the tissues of the porcine
      eye wall are characterized with macrocompression in their layered in vivo
      arrangement. The overall constraints of standardized macroscale tests for dynamic
      mechanical characterization of thin and soft biological tissues are discussed.

PMID- 22656197
TI  - Pittsburgh Conference: the environmental papers.

PMID- 22656196
TI  - Effect of molecular weight on the capillary absorption of polymer droplets.
AB  - We study capillary absorption of small polymer droplets into nonwettable
      capillaries using coarse-grained molecular dynamics simulations and a simple
      analytical model. Studies of droplets of simple fluids have revealed that the
      capillary process depends on the ratio of tube-to-droplet radii [Willmott Faraday
      Discuss., 2010, 146, 233; Marmur J. Colloid Interface Sci. 1988, 122, 209]. Here
      we consider the absorption of droplets of polymers and study the effect of
      polymer chain length on the capillary absorption process. Our simulations reveal
      that for droplets of the same size (radius), the critical tube radius, below
      which there is no absorption, increases with the length of the polymer chains
      that constitute the droplets. We propose a model to explain this effect, which
      incorporates an entropic penalty for polymer confinement and find that this model
      agrees quantitatively with the simulations. We also find that the absorption
      dynamics is sensitive to the polymer chain length. In some cases during the
      capillary uptake transient partial absorption states, where the droplet is
      partially in and partially out of the tube, were observed. Such dynamics cannot
      be explained by a generalized Lucas-Washburn approach.

PMID- 22656198
TI  - Isco.

PMID- 22656199
TI  - Regulatory alert.

PMID- 22656200
TI  - Anodic stripping voltammetry as an analytical tool.

PMID- 22656201
TI  - Acid precipitation in historical perspective.

PMID- 22656202
TI  - Monsanto research corporation.

PMID- 22656204
TI  - WEATHERtronics.

PMID- 22656203
TI  - Research results of organometallic chemistry at an affordable price!

PMID- 22656205
TI  - Indiana university.

PMID- 22656208
TI  - Taking things apart & putting things together.

PMID- 22656206
TI  - Reagent chemicals.

PMID- 22656209
TI  - Fill a staff position on capitol hill.

PMID- 22656210
TI  - International.

PMID- 22656211
TI  - Courses.

PMID- 22656213
TI  - Classified section positions open.

PMID- 22656214
TI  - professional consulting services directory.

PMID- 22656215
TI  - Index to the advertisers in this issue.

PMID- 22656216
TI  - Martek instruments, inc.

PMID- 22656219
TI  - Rockwell international.

PMID- 22656217
TI  - Minamata disease.

PMID- 22656220
TI  - The spawning of the "gray" literature.

PMID- 22656221
TI  - Matheson(r) instruments.

PMID- 22656222
TI  - International.

PMID- 22656223
TI  - Washington.

PMID- 22656224
TI  - State.

PMID- 22656225
TI  - Awards.

PMID- 22656226
TI  - Science.

PMID- 22656227
TI  - Industry.

PMID- 22656229
TI  - The greenhouse effect.

PMID- 22656228
TI  - Technology.

PMID- 22656231
TI  - O.I. Corporation.

PMID- 22656230
TI  - Why maintain biological diversity?

PMID- 22656232
TI  - The persistent PCB problem.

PMID- 22656233
TI  - Blood is thicker: moral spillover effects based on kinship.
AB  - Three empirical studies document the intuitive spillover of moral taint from a
      person who engages in immoral acts to another individual who is related by ties
      of blood kinship. In Study 1, participants were more likely to recommend that the
      biological grandchild of a wrongdoer, compared to a non-biological grandchild,
      help the descendants of his grandfather's victims. In Study 2, participants were
      more willing to hold two long-lost identical twins in custody for a crime
      committed by one twin than to hold two perfect look-alikes for a crime committed
      by one look-alike. Study 3 provides direct evidence that spillover effects based
      on blood kinship are manifested in an intuitive sense of moral taint.

PMID- 22656236
TI  - The Journal of Biomolecular Structure and Dynamics Establishes Web Site: The JBSD
      WWW Edition.

PMID- 22656237
TI  - Cancer Watch Establishes Web Site: The CANCER WATCH WWW Edition.

PMID- 22656234
TI  - Multicenter phase II study of rituximab and temozolomide in recurrent primary
      central nervous system lymphoma.
AB  - We initiated a prospective multicenter phase II trial using rituximab and
      temozolomide in immunocompetent patients with progressive or recurrent primary
      central nervous system lymphoma (PCNSL) based on activity observed in
      retrospective studies. Treatment consisted of an induction phase with rituximab
      (750 mg/m(2)) on days 1, 8, 15 and 22 and temozolomide (150 mg/m(2)) days 1-7 and
      15-21, followed by six cycles of consolidation temozolomide (150-200 mg/m(2) *
      5/28 days), followed by maintenance with methylprednisolone (1 g IV every 28
      days) until progression. Sixteen patients were enrolled, and a complete response
      was seen in 2/14 (14%) evaluable patients. The median progression-free survival
      was 7 weeks and median overall survival was not reached (median follow-up: 37
      months). Treatment was well tolerated, but due to slow accrual and preliminary
      analysis suggesting futility, the trial was closed early. Given the overall
      modest activity, this regimen should be reserved for patients who are not
      candidates for other, more aggressive salvage treatments.

PMID- 22656238
TI  - Tenth Conversation in the Discipline Biomolecular Stereodynamics The University,
      Albany, New York, June 17-21, 1997.

PMID- 22656239
TI  - Biological Structure and Dynamics: Volumes One and Two.

PMID- 22656240
TI  - Contribution to normal tissue dose from concomitant radiation for two common kV
      CBCT systems and one MVCT system used in radiotherapy.
AB  - BACKGROUND AND PURPOSE: This study outlines the measured doses for three
      concomitant imaging modalities used in radiotherapy. MATERIAL AND METHODS: Doses
      were measured using thermo luminescent dosemeters within pelvis and thorax
      anthropomorphic phantoms for the Varian On Board Imager (OBI), Elekta X-ray
      Volume Imager (XVI) and Tomotherapy HiArt II systems. Organ sites were selected
      to include those organs which would be irradiated by the treatment beam during
      the therapy exposure. RESULTS: Doses for kilovoltage imaging systems are
      comparable within the pelvis phantom at 20-30 mGy. Thorax phantom doses are
      lower, especially where user specified protocols are used at 5-10 mGy.
      Tomotherapy doses are typically less than 10 mGy for both phantoms. CONCLUSIONS:
      Concomitant imaging dose is a small fraction of the therapy dose, however, for a
      high fraction technique, the imaging dose can become comparable to the therapy
      dose outside primary target volume. Recommendations for optimisation of imaging
      in radiotherapy are presented.

PMID- 22656241
TI  - Effect of hydrogen bonds on pKa values: importance of networking.
AB  - The pK(a) of an acyclic aliphatic heptaol ((HOCH(2)CH(2)CH(OH)CH(2))(3)COH) was
      measured in DMSO, and its gas-phase acidity is reported as well. This tertiary
      alcohol was found to be 10(21) times more acidic than tert-butyl alcohol in DMSO
      and an order of magnitude more acidic than acetic acid (i.e., pK(a) = 11.4 vs
      12.3). This can be attributed to a 21.9 kcal mol(-1) stabilization of the charged
      oxygen center in the conjugate base by three hydrogen bonds and another 6.3 kcal
      mol(-1) stabilization resulting from an additional three hydrogen bonds between
      the uncharged primary and secondary hydroxyl groups. Charge delocalization by
      both the first and second solvation shells may be used to facilitate enzymatic
      reactions. Acidity constants of a series of polyols were also computed, and the
      combination of hydrogen-bonding and electron-withdrawing substituents was found
      to afford acids that are predicted to be extremely acidic in DMSO (i.e., pK(a) <
      0). These hydrogen bond enhanced acids represent an attractive class of Bronsted
      acid catalysts.

PMID- 22656242
TI  - New insights into the formation of aroma-active strecker aldehydes from 3
      oxazolines as transient intermediates.
AB  - 2-Substituted-5-methyl-3-oxazolines, a novel class of aroma precursors that are
      able to release the respective Strecker aldehydes by hydrolysis, were identified.
      Hydrolysis can take place after the addition of water or with human saliva during
      mastication, respectively. 2-Isobutyl-, 2-sec-isobutyl-, 2-isopropyl, and 2
      benzyl-5-methyl-3-oxazolines were synthesized and structurally identified by
      means of gas chromatography-mass spectrometry (GC-MS) in the electron impact mode
      and in the chemical ionization mode as well as by one- and two-dimensional NMR
      experiments. With these compounds at hand, a variety of stability experiments
      were performed using headspace-GC-MS or proton transfer reaction-MS techniques on
      the basis of stable isotope dilution assays, proving the ability to release the
      respective Strecker aldehydes was dependent on the pH value as well as on the
      hydrolysis time. After the addition of water at 37  degrees C, for example, >70
      mol % of 3-methylbutanal or >40 mol % of phenylacetaldehyde was liberated from a
      solution of 2-isobutyl-5-methyl-3-oxazoline or 2-benzyl-5-methyl-3-oxazoline,
      respectively, after 5 min. Furthermore, the presence of 2-isobutyl-5-methyl-3
      oxazoline in dark chocolate containing 70% cocoa was proven by GC-MS.

PMID- 22656243
TI  - The hygienic efficacy of different hand-drying methods: a review of the evidence.
AB  - The transmission of bacteria is more likely to occur from wet skin than from dry
      skin; therefore, the proper drying of hands after washing should be an integral
      part of the hand hygiene process in health care. This article systematically
      reviews the research on the hygienic efficacy of different hand-drying methods. A
      literature search was conducted in April 2011 using the electronic databases
      PubMed, Scopus, and Web of Science. Search terms used were hand dryer and hand
      drying. The search was limited to articles published in English from January 1970
      through March 2011. Twelve studies were included in the review. Hand-drying
      effectiveness includes the speed of drying, degree of dryness, effective removal
      of bacteria, and prevention of cross-contamination. This review found little
      agreement regarding the relative effectiveness of electric air dryers. However,
      most studies suggest that paper towels can dry hands efficiently, remove bacteria
      effectively, and cause less contamination of the washroom environment. From a
      hygiene viewpoint, paper towels are superior to electric air dryers. Paper towels
      should be recommended in locations where hygiene is paramount, such as hospitals
      and clinics.

PMID- 22656244
TI  - National asthma observational survey of severe asthmatics in Israel: the no-air
      study.
AB  - BACKGROUND: Asthma is considered a global public health issue requiring a
      significant medical expenditure as a result of its high prevalence and the low
      rate of disease control. OBJECTIVE: This is the first nationwide survey of severe
      asthma patients carried out in Israel. In this study we aimed to assess health
      resources utilization, compliance with treatment and disease-control in a
      subgroup of patients with severe asthma in Israel. MATERIAL AND METHOD: One
      hundred and twenty-three patients with a diagnosis of asthma for more then one
      year, as well as a hospitalization during the last 12 months due to asthma
      exacerbation or maintenance systemic steroids therapy, were included in this non
      interventional observational study. RESULTS: Asthma was uncontrolled in 43.9%,
      partly controlled in 50.4% and well controlled in only 5.7%. The majority of the
      patients (83%) were compliant with drug treatment. CONCLUSION: The fact that 83%
      of the asthma patients included in this study were compliant with their asthma
      therapy was not manifested in asthma control. Therefore concrete tools are
      required for achieving and maintaining asthma control, especially in the
      treatment of the most severe asthmatic patients.

PMID- 22656245
TI  - MPO-ANCA associated crescentic glomerulonephritis with numerous immune complexes:
      case report.
AB  - BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated crescentic
      glomerulonephritis (CGN) is a major cause of rapidly progressive
      glomerulonephritis (RPGN). ANCA-associated CGN is generally classified into pauci
      immune RPGN, in which there are few or no immune complexes. CASE PRESENTATION: A
      78-year-old man presented with RPGN after a 7-year course of chronic proteinuria
      and hematuria with stable renal function. A blood examination showed a high titer
      of myeloperoxidase (MPO)-ANCA. A renal biopsy showed crescentic
      glomerulonephritis with abundant subepithelial, intramenbranous and
      subendothelial deposits by electron microscopy, leading to the diagnosis of ANCA
      associated CGN superimposed on type 3 membranoproliferative glomerulonephritis
      (MPGN). CONCLUSIONS: This case is unique in that type 3 MPGN and MPO-ANCA
      associated CGN coexisted, and no similar case has been reported to date. Because
      ANCA-associated CGN has a predilection for elderly individuals and primary type 3
      MPGN is rarely seen in this age group, coincidental existence appears less
      likely. This case may confer valuable information regarding the link between
      immune complex and ANCA-associated CGN.

PMID- 22656246
TI  - Craniocervical fusions in children.
AB  - The surgical management of craniovertebral junction (CVJ) instability in
      pediatric patients presents unique challenges. As compared with the adult
      patient, the anatomical variations of the CVJ in the pediatric patient are
      significant, complicate the approach, and limit the use of internal fixation.
      Diminutive osseous and ligamentous structures and syndromic craniovertebral
      abnormalities complicate the issue. Advances in imaging analysis and
      instrumentation have improved the armamentarium for managing the pediatric
      patient who requires craniocervical stabilization. In this paper, the author's
      experience of performing more than 850 pediatric CVJ fusions is reviewed. This
      work includes the indications for atlantoaxial arthrodesis and occipitocervical
      fusion. Early atlantoaxial fusions were performed using interlaminar rib graft
      fusion, and more recently using either transarticular screw fixation in the older
      patient, or lateral mass screws at C-1 and rod fixation with either C-2 pars
      interarticular screw fixation or pedicle screw fixation. A C-2 translaminar screw
      fixation is also described. Occipitocervical fusions are performed with rib
      grafts in patients younger than 6 years of age. Subsequently, above that age,
      contoured loop fixation was performed, and in the past 8-10 years, screw and rod
      fixation was used. Abnormal spine growth was not observed in children who
      underwent craniocervical stabilization below the age of 5 years (clearly the bone
      grew with the patient). However, no deleterious effects were noted in the
      children treated with rigid instrumentation. The success rate for bone fusion
      alone was 98%. The author's success rate with rigid instrumentation is nearly
      100%. A detailed review of the technique of fusion is presented, as well as the
      indications and means of avoidance of complications, their prevention, and
      management.

PMID- 22656247
TI  - Complications of occipital screw placement for occipitocervical fusion in
      children.
AB  - OBJECT: Occipitocervical stabilization in the pediatric age group remains a
      challenge because of the regional anatomy, poor occipital bone purchase, and, in
      some instances, significant thinning of the occipital bone. Multiple bicortical
      fixation points to the occipital bone may be required to increase construct
      rigidity. The authors evaluated the complications of bicortical occipital screw
      placement in children with occipital fusion constructs. METHODS: The records of
      20 consecutive pediatric patients who had undergone occipitocervical fusion
      between September 1, 2007, and November 30, 2010, at Texas Children's Hospital
      were reviewed. RESULTS: The patients consisted of 10 girls and 10 boys, ranging
      in age from 10 months to 16 years (mean +/- SD, 7.7 +/- 5.1 years). Two patients
      were lost to follow-up, 2 died for reasons unrelated to the surgery, and the
      remaining patients had at least 3 months of follow-up (mean 14 +/- 11.8 months)
      with evaluation via dynamic radiography and CT. Four patients experienced 8
      complications: 2 CSF leaks, 2 vigorous venous bleedings, worsening of
      quadriparesis, wound infection, radiographic pseudarthrosis, and transient
      dysphagia. Among 114 screws, there were 2 cases of intraoperative dural venous
      sinus injury and 2 cases of intraoperative CSF leakage, without clinical sequelae
      from these complications. Only 1 case of radiographic pseudarthrosis was
      identified in a patient with skeletal dysplasia and a prior failed C1-2 posterior
      arthrodesis. There were no difficulties with wound healing because of prominent
      occipital instrumentation, and there was only 1 wound infection. CONCLUSIONS:
      Data in this report confirm that including bicortical occipital screw placement
      in occipitocervical constructs in children may result in a high fusion rate but
      at the cost of a notable complication rate.

PMID- 22656248
TI  - Complex pediatric cervical spine surgery using smaller nonspinal screws and
      plates and intraoperative computed tomography.
AB  - OBJECT: The treatment of craniocervical instability in children is often
      challenging due to their small spine bones, complex anatomy, and unique
      syndromes. The authors discuss their surgical experience with 33 cases in the
      treatment of 31 children (<= 17 years of age) with craniocervical spine
      instability using smaller nontraditional titanium screws and plates, as well as
      intraoperative CT. METHODS: All craniocervical fusion procedures were performed
      using intraoperative fluoroscopic imaging and electrophysiological monitoring.
      Nontraditional spine hardware included smaller screw sizes (2.4 and 2.7 mm) from
      the orthopedic hand/foot set and mandibular plates. Twenty-three of the 33
      surgical procedures were performed with intraoperative CT, which was used to
      confirm adequate position of the spine hardware and alignment of the spine.
      RESULTS: The mean patient age was 9.5 years (range 2-17 years). Eleven children
      underwent a posterior C1-2 transarticular screw fusion, 17 had an
      occipitocervical fusion, and 3 had a posterior subaxial cervical fusion. The
      follow-up duration ranged from 9 to 72 months (mean 53 months). All children
      demonstrated successful fusion at their 3-month follow-up visit, except 1 patient
      whose unilateral C1-2 transarticular screw fusion required a repeat surgery
      before proper fusion was achieved. Of the 47 C1-2 transarticular screws that were
      placed, 13 were 2.4 mm, 15 were 2.7 mm, 7 were 3.5 mm, and 12 were 4.0 mm.
      Eighteen of the 47 C1-2 transarticular screws were suboptimally placed. Eleven of
      these misplaced screws were removed and redirected within the same operation
      because these surgeries benefitted from the use of intraoperative CT; 6 of the 7
      remaining suboptimally placed screws were left in place because a second surgery
      for screw replacement was not warranted. The other suboptimally placed C1-2 screw
      was replaced during a repeat operation due to failure of fusion. Use of
      intraoperative CT was invaluable because it enabled the authors to reposition
      suboptimal C1-2 transarticular screws without necessitating a second operation.
      CONCLUSIONS: Successful craniocervical fusion procedures were achieved using
      smaller nontraditional titanium screws and plates. Intraoperative CT was a
      helpful adjunct for confirming and readjusting the trajectory of the screws prior
      to leaving the operating room, which decreases overall treatment costs and
      reduces complications.

PMID- 22656249
TI  - Sacroiliac joint pain in the pediatric population.
AB  - OBJECT: The sacroiliac (SI) joint can be a pain generator in 13%-27% of cases of
      back pain in adults. These numbers are largely unknown for the pediatric
      population. In children and especially girls, development of the pelvic girdle
      makes the SI joint prone to misalignment. Young athletes sustain repeated stress
      on their SI joints, and sometimes even minor trauma can result in lasting pain
      that mimics radiculopathy. The authors present a series of 48 pediatric patients
      who were evaluated for low-back pain and were found to have SI joint misalignment
      as the cause of their symptoms. They were treated with a simple maneuver
      described in this paper that realigned their SI joint and provided significant
      improvement of symptoms. METHODS: A retrospective review of the electronic
      records identified 48 patients who were referred with primary complaints of low
      back pain and were determined to have SI joint misalignment during bedside
      examination maneuvers described here. Three patients did not have a record of
      their response to treatment and were excluded. Patients were evaluated by a
      physical therapist and had the realignment procedure performed on the day of
      initial consultation. The authors collected data regarding the immediate effect
      of the procedure, as well as the duration of pain relief at follow-up visits.
      RESULTS: Eighty percent of patients experienced dramatic improvement in symptoms
      that had a lasting effect after the initial treatment. The majority of them were
      given a home exercise program, and only 2 of the 36 patients who experienced
      significant relief had to be treated again. Fifty-three percent of all patients
      had immediate and complete resolution of symptoms. Three of the 48 patients had
      missing data from the medical records and were excluded from computations.
      CONCLUSIONS: Back pain is multifactorial, and the authors' data demonstrate the
      potential importance of SI joint pathology. Although the technique described here
      for treatment of misaligned SI joints in the pediatric patients is not effective
      in all, the authors have observed significant improvement in 80% of cases. Often
      it is difficult to determine the exact cause of back pain, but when the SI joint
      is suspected as the primary pathology, the authors have described a simple and
      effective bedside treatment that should be attempted prior to the initiation of
      further testing and surgery.

PMID- 22656250
TI  - Spinal cord infarction remote from maximal compression in a patient with Morquio
      syndrome.
AB  - Morquio syndrome, or mucopolysaccharidosis type IV, is a rare enzyme deficiency
      disorder and results in skeletal dysplasia. Odontoid dysplasia is common among
      affected patients, resulting in atlantoaxial instability and spinal cord
      compression. Surgical treatments include decompression and prophylactic fusion,
      during which intraoperative neuromonitoring is important to alert the surgical
      team to changes in cord function so that they can prevent or mitigate spinal cord
      injury. This report describes a 16-year-old girl with Morquio syndrome who
      developed paraplegia due to thoracic spinal cord infarction during foramen magnum
      and atlantal decompression. This tragic event demonstrates the following: 1) that
      patients with Morquio syndrome are at risk for ischemic spinal cord injury at
      levels remote from areas of maximal anatomical compression while under anesthesia
      in the prone position, possibly due to impaired cardiac output; 2) the
      significance of absent motor evoked potential responses in the lower limbs with
      preserved upper-limb responses in an ambulatory patient; 3) the importance of
      establishing intraoperative neuromonitoring baseline assessments prior to turning
      patients to the prone position following induction of anesthesia; and 4) the
      importance of monitoring cardiac output during prone positioning in patients with
      chest wall deformity.

PMID- 22656251
TI  - Abdominal binders.

PMID- 22656252
TI  - The use of abdominal binders to treat over-shunting headaches.
AB  - OBJECT: Headaches are common in children with shunts. Headaches associated with
      over-shunting are typically intermittent and tend to occur later in the day.
      Lying down frequently makes the headaches better. This paper examines the
      efficacy of using abdominal binders to treat over-shunting headaches. METHODS:
      Over an 18-year period, the senior author monitored 1027 children with shunts.
      Office charts of 483 active patients were retrospectively reviewed to identify
      those children with headaches and, in particular, those children who were thought
      to have headaches as a result of over-shunting. Abdominal binders were frequently
      used to treat children with presumed over-shunting headaches, and these data were
      analyzed. RESULTS: Of the 483 patients undergoing chart review, 258 (53.4%) had
      headache. A clinical diagnosis of over-shunting was made in 103 patients (21.3%
      overall; 39.9% of patients with headache). In 14 patients, the headaches were
      very mild (1-2 on a 5-point scale) and infrequent (1 or 2 per month), and
      treatment with an abdominal binder was not thought indicated. Eighty-nine
      patients were treated with a binder, but 19 were excluded from this retrospective
      study for noncompliance, interruption of the binder trial, or lack of follow-up.
      The remaining 70 pediatric patients, who were diagnosed with over-shunting
      headaches and were treated with abdominal binders, were the subjects of a more
      detailed retrospective study. Significant headache improvement was observed in
      85.8% of patients. On average, the patients wore the binders for approximately 1
      month, and headache relief usually persisted even after the binders were
      discontinued. However, the headaches eventually did recur in many of the patients
      more than a year later. In these patients, reuse of the abdominal binder was
      successful in relieving headaches in 78.9%. CONCLUSIONS: The abdominal binder is
      an effective, noninvasive therapy to control over-shunting headaches in most
      children. This treatment should be tried before any surgery is considered. It is
      suggested that the abdominal binder may modulate abnormally increased
      intracranial pulse pressures associated with over-shunting. Interactions with the
      cerebrovascular bed are suspected to account for persistent headache relief after
      the binder is discontinued.

PMID- 22656253
TI  - Clinical evaluation and surveillance imaging in children with spina bifida aperta
      and shunt-treated hydrocephalus.
AB  - OBJECT: Most children with spina bifida aperta have implanted CSF shunts.
      However, the efficacy of adding surveillance imaging to clinical evaluation
      during routine follow-up as a means to minimize the hazard of shunt failure has
      not been thoroughly studied. METHODS: A total of 396 clinic visits were made by
      patients with spina bifida aperta and shunt-treated hydrocephalus in a spina
      bifida specialty clinic during the calendar years 2008 and 2009 (initial clinic
      visit). All visits were preceded by a 6-month period during which no shunt
      evaluation of any kind was performed and were followed by a subsequent visit in
      the same clinic. At the initial clinic visit, 230 patients were evaluated by a
      neurosurgeon (clinical evaluation group), and 166 patients underwent previously
      scheduled surveillance CT scans in addition to clinical evaluation (surveillance
      imaging group). Subsequent unexpected events, defined as emergency department
      (ED) visits and caregiver-requested clinic visits, were reviewed. The time to an
      unexpected event and the likelihood of event occurrence in each of the 2 groups
      were compared using Cox proportional hazards survival analysis. The outcome and
      complications of shunt surgeries were also reviewed. RESULTS: The clinical
      characteristics of the 2 groups were similar. In the clinical evaluation group, 2
      patients underwent shunt revision based on clinical findings in the initial
      visit. In the subsequent follow-up period, there were 27 visits to the ED and 25
      requested clinic visits that resulted in 12 shunt revisions. In the surveillance
      imaging group, 11 patients underwent shunt revision based on clinical and imaging
      findings in the initial visit. In the subsequent follow-up period, there were 15
      visits to the ED and 9 requested clinic visits that resulted in 8 shunt
      revisions. Patients who underwent surveillance imaging on the day of initial
      clinic visit were less likely to have an unexpected event in the subsequent
      follow-up period (relative risk 0.579, p = 0.026). The likelihood of needing
      shunt revision and the morbidity of shunt malfunction was not significantly
      different between the 2 groups. CONCLUSIONS: Surveillance imaging in children
      with spina bifida aperta and shunted hydrocephalus decreases the likelihood of ED
      visits and caregiver-requested clinic visits in the follow-up period, but based
      on this study, its effect on mortality and morbidity related to shunt malfunction
      was less clear.

PMID- 22656254
TI  - Split cord malformation Type II with twin dorsal lipomas.
AB  - Although uncommon, variations in split cord malformation (SCM) have been
      described. However, a combination of SCM Type II and dorsal lipomas has not been
      reported.   The authors describe the case of a 6-year-old girl who presented with
      a 1-year history of spastic paraparesis associated with a lipomatous swelling on
      her lower back. Radiology revealed a Type II SCM with a dorsal lipoma at that
      level. Intraoperatively, the authors observed a dorsal lipoma for each hemicord;
      these were excised, and the septum causing the split was cut.   Premature
      separation of the cutaneous and neural ectoderm is predetermined for each neural
      fold, and a split at this level would give rise to SCM with twin dorsal lipomas,
      one for each hemicord.

PMID- 22656255
TI  - Longitudinal comparison of diffusion tensor imaging parameters and
      neuropsychological measures following endoscopic third ventriculostomy for
      hydrocephalus.
AB  - The authors report the case of a 25-month-old boy who underwent endoscopic third
      ventriculostomy (ETV) for hydrocephalus resulting from aqueductal stenosis. The
      patient's recovery was monitored longitudinally and prospectively using MR
      diffusion tensor imaging (DTI) and formal neuropsychological testing. Despite
      minimal change in ventricle size, improvement in the DTI characteristics and
      neurodevelopmental trajectory was observed following ETV. These data support the
      use of DTI as a biomarker to assess therapeutic response in children undergoing
      surgical treatment for hydrocephalus. In the patient featured in this report, DTI
      appeared to provide more information regarding postoperative neurodevelopmental
      outcome than ventricle size alone.

PMID- 22656256
TI  - Long-term outcome of 114 children with cerebral aneurysms.
AB  - OBJECT: Population-based data on pediatric patients with aneurysms are limited.
      The aim of this study is to clarify the characteristics and long-term outcomes of
      pediatric patients with aneurysms. METHODS: All pediatric patients (<= 18 years
      old) with aneurysms among the 8996 aneurysm patients treated at the Department of
      Neurosurgery in Helsinki from 1937 to 2009 were followed from admission to the
      end of 2010. RESULTS: There were 114 pediatric patients with 130 total aneurysms
      during the study period. The mean patient age was 14.5 years (range 3 months to
      18 years). The male:female ratio was 3:2. Eighty-nine patients (78%) presented
      with subarachnoid hemorrhage. The majority of the aneurysms (116 [89%]) were in
      the anterior circulation, and the most common location was the internal carotid
      artery bifurcation (36 [28%]). The average aneurysm diameter was 11 mm (range 2
      55 mm) with 16 giant aneurysms (12%). Eighty aneurysms (62%) were treated
      microsurgically, and 37 (28%) were treated conservatively due to poor medical and
      neurological status of the patient or due to technical reasons during the early
      years of the patient series. No connective tissue disorders common to pediatric
      aneurysm patients were diagnosed in this series, with the exception of 1 patient
      with tuberous sclerosis complex. The mean follow-up duration was 24.8 years
      (range 0-55.8 years). At the end of follow-up, 71 patients (62%) had a good
      outcome, 3 (3%) were dependent, and 40 (35%) had died. Twenty-seven deaths (68%)
      were assessed to be aneurysm-related. Factors correlating with a favorable long
      term outcome were good neurological condition of the patient on admission,
      aneurysm location in the anterior circulation, complete aneurysm closure, and
      absence of vasospasm. Six patients developed symptomatic de novo aneurysms after
      a median of 25 years (range 11-37 years). Fourteen patients (12%) had a family
      history of aneurysms. There was no increased incidence for cardiovascular
      diseases in long-term follow-up. CONCLUSIONS: Most aneurysms were ruptured and of
      medium size. Internal carotid artery bifurcation was the most frequent location
      of the aneurysms. There was a male predominance of pediatric patients with
      aneurysms. Most patients experienced good recovery, with 91% of the long-term
      survivors living at home independently without assistance and meaningfully
      employed. Altogether, almost a third of these patients finished high school and
      one-fifth had a college or university degree. Pediatric patients had a tendency
      to develop de novo aneurysms.

PMID- 22656257
TI  - Spinal cord ependymomas and myxopapillary ependymomas in the first 2 decades of
      life: a clinicopathological and immunohistochemical characterization of 19 cases.
AB  - OBJECT: Primary spinal cord ependymomas (EPNs) are rare in children, comprising
      classical WHO Grade II and III tumors and Grade I myxopapillary ependymomas
      (MEPNs). Despite their benign histology, recurrences and neural-axis
      dissemination have been reported in up to 33% MEPNs in the pediatric population.
      Treatment options beyond resection are limited, and little is known about their
      tumorigenesis. The purpose of this study was to explore the tumor biology and
      outcomes in a consecutive series of pediatric patients treated at a single
      institution. METHODS: The authors performed a retrospective clinicopathological
      review of 19 patients at a tertiary referral children's hospital for resection of
      a spinal cord ependymoma. The population included 8 patients with a pathological
      diagnosis of MEPN and 11 patients with a pathological diagnosis of spinal EPN (10
      cases were Grade II and 1 case was Grade III). The upregulation of the following
      genes HOXB13, NEFL, PDGFRalpha, EGFR, EPHB3, AQP1, and JAGGED 1 was studied by
      immunohistochemistry from archived paraffin-embedded tumor samples of the entire
      cohort to compare the expression in MEPN versus EPN. RESULTS: Gross-total
      resection was achieved in 75% of patients presenting with MEPNs and in 100% of
      those with EPNs. The average follow-up period was 79 months for the MEPN subset
      and 53 months for Grade II/III EPNs. Overall survival for both subsets was 100%.
      However, event-free survival was only 50% for patients with MEPNs. Of note, in
      all cases involving MEPNs that recurred, the patients had undergone gross-total
      resection on initial surgery. In contrast, there were no tumor recurrences in
      patients with EPNs. Immunohistochemistry revealed no significant differences in
      protein expression between the two tumor types with the exception of EPHB3, which
      demonstrates a tendency to be positive in MEPNs (6 reactive tumors of 9) rather
      than in EPN (2 reactive tumors of 10). CONCLUSIONS: The authors' experience shows
      that, following a gross-total resection, MEPNs are more likely to recur than
      their higher-grade counterpart, EPNs. This supports the recommendation for close
      long-term radiological follow-up of pediatric patients with MEPNs to monitor for
      recurrence, despite the tumor's low-grade histological feature. No significant
      difference in the protein expression of HOXB13, NEFL, PDGFRalpha, EGFR, EPHB3,
      AQP1, and JAGGED 1 was present in this selected cohort of pediatric patients.

PMID- 22656258
TI  - Spinal arteriovenous fistulas in children with hereditary hemorrhagic
      telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant
      angiodysplasia with high penetrance and variable expression. The manifestations
      of HHT are often age related, and spinal arteriovenous fistula (AVF) may be the
      initial presentation of HHT in young children. Because spinal AVFs are rarely
      reported, however, screening is not incorporated into current clinical
      recommendations for the treatment of patients with HHT. The authors describe 2
      cases of children younger than 2 years of age with acute neurological
      deterioration in the context of a spinal AVF and in whom HHT was subsequently
      diagnosed. One patient presented with intraventricular and subarachnoid
      hemorrhage and the other with acute thrombosis of an intramedullary varix. These
      cases highlight the potential for significant neurological morbidity from a
      symptomatic AVF in very young children with HHT. Given the lack of data regarding
      the true incidence and natural history of these lesions, these cases raise the
      question of whether spinal cord imaging should be incorporated into screening
      recommendations for patients with HHT.

PMID- 22656259
TI  - First preoperative functional mapping via navigated transcranial magnetic
      stimulation in a 3-year-old boy.
AB  - Preoperative functional mapping in children younger than 5 years old remains a
      challenge. Awake functional MRI (fMRI) is usually not an option for these
      patients. Except for a description of passive fMRI in sedated patients and
      magnetoencephalography, no other noninvasive mapping method has been reported as
      a preoperative diagnostic tool in children. Therefore, invasive intraoperative
      direct cortical stimulation remains the method of choice. To the authors'
      knowledge, this is the first case of a young child undergoing preoperative
      functional motor cortex mapping with the aid of navigated transcranial magnetic
      stimulation (nTMS).   In this 3-year-old boy with a rolandic ganglioglioma, awake
      preoperative mapping was performed using nTMS. A precise location of Broca area 4
      could be established. The surgical approach was planned according to the
      preoperative findings. Intraoperative direct cortical stimulation verified the
      location of the nTMS hotspots, and complete resection of the precentral tumor was
      achieved.   Navigated TMS is a precise tool for preoperative motor cortex mapping
      and is feasible even in very young pediatric patients. In children for whom
      performing the fMRI motor paradigm is challenging, nTMS is the only available
      option for functional mapping.

PMID- 22656260
TI  - Unplanned reoperation rates in pediatric neurosurgery: a single center experience
      and proposed use as a quality indicator.
AB  - OBJECT: The pediatric neurosurgery practice over 2 years was reviewed at a
      tertiary neurosciences center. The intention was to establish the frequency of
      unplanned reoperations at the center, investigate the factors responsible, and
      consider using unplanned reoperations as a quality indicator. METHODS: All
      pediatric neurosurgical operations done between January 2008 and January 2010
      were reviewed using data from operation theater logs and hospital records. Data
      were recorded as per the standard requirements of the Society of British
      Neurological Surgeons for incorporation into the national database. "Unplanned
      reoperation" was defined as any unscheduled secondary procedure required for a
      complication resulting directly or indirectly from the index operation or as an
      unscheduled return to the operating theater for the same condition. Operations
      were defined as "urgent" if they had to be performed out of hours (that is,
      outside the hours of 8:00 a.m. to 5:00 p.m.), "emergency elective" if they were
      included on the emergency list but within working hours, and "routine elective"
      if they were on the scheduled operations list. Both overall and 30-day unplanned
      reoperation rates were considered. Factors influencing unplanned reoperations
      were explored using a logistic regression model. RESULTS: Four hundred ten
      operations were analyzed. The overall unplanned reoperation rate was 28%. The
      median time to an unplanned reoperation was 9 days. Risk factors for unplanned
      reoperations included a CSF diversion procedure (OR 7, p < 0.0001) and an urgent
      procedure (OR 2.5, p = 0.02, higher unplanned reoperations for urgent procedures
      relative to routine electives). The 30-day unplanned reoperation rate was 17%.
      Urgent cases composed 32% of all operations. Trainees performed 52% of the urgent
      operations. Forty-four percent of all operations were related to CSF diversion.
      Sixty-four percent of patients had reoperations during the course of the study
      period, and 44% of these reoperations were unplanned. CONCLUSIONS: An unplanned
      return to the operation theater is common in the authors' pediatric neurosurgical
      practice and is procedure specific. Unplanned reoperation rates may be useful for
      monitoring quality across hospitals and identifying opportunities for quality
      improvement. The authors propose the use of this index as a quality indicator and
      advocate its validation in a prospective multicenter study.

PMID- 22656261
TI  - Growing skull fracture stages and treatment strategy.
AB  - OBJECT: A growing skull fracture (GSF) is a rare but significant late
      complication of skull fractures, usually occurring during infancy and early
      childhood. Delayed diagnosis and improper treatment could exacerbate this
      disease. The aim of this study was to introduce a new hypothesis about, describe
      the stages of, and discuss the treatment strategy for GSF. METHODS: The authors
      performed a retrospective review of 27 patients with GSF, who were grouped
      according to 3 different GSF stages. RESULTS: Over a period of 20 years, 27
      patients with GSF (16 males and 11 females) were treated in the authors'
      department. The mean follow-up period was 26.5 months. Six patients were in the
      prephase of GSF (Stage 1), 10 patients in the early phase (Stage 2), and 11 in
      the late phase (Stage 3). All patients underwent duraplasty. All 6 patients at
      Stage 1 and 5 patients at Stage 2 underwent craniotomy without cranioplasty. Five
      patients at Stage 2 and all of the patients at Stage 3 underwent cranioplasty
      with autologous bone and alloplastic materials, respectively. Among all patients,
      5 underwent ventriculoperitoneal shunt placement. Symptoms in all patients at
      Stages 1 and 2 were alleviated or disappeared, and the cranial bones developed
      without deformity during follow-up. Among patients with Stage 3 GSF, no obvious
      improvement in neurological deficits was observed. Three patients underwent
      additional operations because of cranial deformation or infection. CONCLUSIONS:
      The authors identify the stages of GSF according to a new hypothesis. They
      conclude that accurately diagnosing and treating GSF during Stages 1 and 2 leads
      to a better prognosis.

PMID- 22656262
TI  - Treatment of depressed skull fractures in neonates using percutaneous microscrew
      elevation.
AB  - Depressed skull fractures in neonates involve the inward buckling of the skull
      bones to resemble a cup shape or "ping-pong ball" shape. In the past, several
      methods have been used to treat these fractures for cosmetic effect, including
      the use of vacuum extraction. The aim of this study was to demonstrate the use of
      a novel treatment method for these skull fractures. All patients presented to
      Hershey Medical Center between May 2007 and March 2010. All underwent treatment
      of their ping-pong skull fracture using a novel technique of percutaneous screw
      elevation with self-tapping microscrews (4 or 5 mm) typically used in
      neurosurgery for cranial plating. Four patients were treated, all between the
      ages of 2 days and 4 months. Two of the patients were treated under general
      anesthesia and 2 with local anesthesia only. All patients had good cosmetic
      results and experienced no adverse events. Percutaneous screw elevation of the
      ping-pong type, simple depressed skull fracture in neonates is a feasible method
      of treatment with a low complication rate associated with the procedure and no
      risk from anesthesia.

PMID- 22656263
TI  - Helmets and synostosis.

PMID- 22656264
TI  - Complexation using direct current: novel batch method for drug-resinate
      preparation.
AB  - Pharmaceutically, resinates are used for the development of drug delivery
      technologies including targeted drug delivery, taste masking, dissolution
      improvement of drug and its stabilization. Laboratory methods used for the
      preparation of resinates involve the reaction between drug and ion exchange
      polymer by column or batch process. Present study investigated the effect of
      electric current (0.1-10 mA) on the complexation of drug, verapamil hydrochloride
      (model drug) with resin. Direct current (DC) (1 mA) applied during activation or
      complexation alone or both demonstrated significant increase in verapamil
      hydrochloride-resin complexation as compare to conventional methods. Moreover,
      further increase in intensity of current above 1 mA failed to increase the drug
      binding. This study suggests the use of electric current as a novel batch method
      for the preparation of drug-resinates.

PMID- 22656266
TI  - Editorial--Molecular Approaches to Malaria 2012 (MAM 2012).

PMID- 22656265
TI  - Stochastic synchronization of neuronal populations with intrinsic and extrinsic
      noise.
AB  - We extend the theory of noise-induced phase synchronization to the case of a
      neural master equation describing the stochastic dynamics of an ensemble of
      uncoupled neuronal population oscillators with intrinsic and extrinsic noise. The
      master equation formulation of stochastic neurodynamics represents the state of
      each population by the number of currently active neurons, and the state
      transitions are chosen so that deterministic Wilson-Cowan rate equations are
      recovered in the mean-field limit. We apply phase reduction and averaging methods
      to a corresponding Langevin approximation of the master equation in order to
      determine how intrinsic noise disrupts synchronization of the population
      oscillators driven by a common extrinsic noise source. We illustrate our analysis
      by considering one of the simplest networks known to generate limit cycle
      oscillations at the population level, namely, a pair of mutually coupled
      excitatory (E) and inhibitory (I) subpopulations. We show how the combination of
      intrinsic independent noise and extrinsic common noise can lead to clustering of
      the population oscillators due to the multiplicative nature of both noise sources
      under the Langevin approximation. Finally, we show how a similar analysis can be
      carried out for another simple population model that exhibits limit cycle
      oscillations in the deterministic limit, namely, a recurrent excitatory network
      with synaptic depression; inclusion of synaptic depression into the neural master
      equation now generates a stochastic hybrid system.

PMID- 22656267
TI  - Relativistic density functional study on uranium(IV) and thorium(IV) oxide
      clusters of zonohedral geometry.
AB  - Free and ligated oxide clusters of thorium(IV) and uranium(IV) were studied with
      density functional theory using all-electron scalar relativistic method, as well
      as energy-consistent relativistic f-in-core pseudopotentials. The main driving
      force for the cluster formation is the sintering of the dioxoactinide moieties,
      which is more favorable for thorium(IV) than for uranium(IV) because, for the
      latter, a penalty for bending of the uranyl(IV) is to be paid. We assumed that
      the rhombic structural motif that exists already in the (AnO(2))(2) dimer could
      be a guide to explaining the preference for the existing An(6)O(8)-type clusters.
      On the basis of this, we have theoretically explored the possibility of the
      existence of similar (zonohedric) polyhedral actinide oxide clusters and found
      that the next possible cluster would be of An(12)O(20) stoicheometry. We have
      predicted by our DFT computations that the corresponding zonohedral clusters
      would be minima on the potential energy surface. The alternating An-O rhombic
      structural motif also offers a possible explanation of the existence and
      stoichiometry of the only nonfluorite cluster thus far, the An(12)O(20), which is
      nonzonohedral, nonconvex, but still a rhombic polyhedron. Our relativistic all
      electron DFT computations of both free cationic and ligated clusters predict that
      preparation of the larger clusters is not forbidden thermodynamically. We have
      also found that for the uranium(IV), oxide dimer and hexamer clusters are
      antiferromagnetic, broken spin singlet in their ground state, while ligated
      [U(6)O(8)] clusters prefer an all high-spin electronic configuration.

PMID- 22656268
TI  - Label free screening of enzyme inhibitors at femtomole scale using segmented flow
      electrospray ionization mass spectrometry.
AB  - Droplet-based microfluidics is an attractive platform for screening and
      optimizing chemical reactions. Using this approach, it is possible to reliably
      manipulate nanoliter volume samples and perform operations such as reagent
      addition with high precision, automation, and throughput. Most studies using
      droplet microfluidics have relied on optical techniques to detect the reaction;
      however, this requires engineering color or fluorescence change into the reaction
      being studied. In this work, we couple electrospray ionization mass spectrometry
      (ESI-MS) to nanoliter scale segmented flow reactions to enable direct (label
      free) analysis of reaction products. The system is applied to a screen of
      inhibitors for cathepsin B. In this approach, solutions of test compounds
      (including three known inhibitors) are arranged as an array of nanoliter droplets
      in a tube segmented by perfluorodecalin. The samples are pumped through a series
      of tees to add enzyme, substrate (peptides), and quenchant. The resulting
      reaction mixtures are then infused into a metal-coated, fused silica ESI emitter
      for MS analysis. The system has potential for high-throughput as reagent addition
      steps are performed at 0.7 s per sample and ESI-MS at up to 1.2 s per sample.
      Carryover is inconsequential in the ESI emitter and between 2 and 9% per reagent
      addition depending on the tee utilized. The assay was reliable with a Z-factor of
      ~0.8. The method required 0.8 pmol of test compound, 1.6 pmol of substrate, and 5
      fmol of enzyme per reaction. Segmented flow ESI-MS allows direct, label free
      screening of reactions at good throughput and ultralow sample consumption.

PMID- 22656270
TI  - Independently controlling protein dot size and spacing in particle lithography.
AB  - Particle lithography is a relatively simple, inexpensive technique used to
      pattern inorganics, metals, polymers, and biological molecules on the micro- and
      nanometer scales. Previously, we used particle lithography to create hexagonal
      patterns of protein dots in a protein resistant background of methoxy
      poly(ethylene glycol)-silane (mPEG-sil). In this work, we describe a simple
      heating procedure to overcome a potential limitation of particle lithography: the
      simultaneous change in feature size and center-to-center spacing as the diameter
      of the spheres used in the lithographic mask is changed. Uniform heating was used
      to make single-diameter protein patterns with dot sizes of approximately 2-4 or 2
      8 MUm, depending on the diameter of the spheres used in the lithographic mask,
      while differential heating was used to make a continuous gradient of dot sizes of
      approximately 1-9 MUm on a single surface. We demonstrate the applicability of
      these substrates by observing the differences in neutrophil spreading on
      patterned and unpatterned protein coated surfaces.

PMID- 22656269
TI  - Changes in aortic shape and diameters after death: comparison of early postmortem
      computed tomography with antemortem computed tomography.
AB  - PURPOSE: The purpose of this study is to evaluate the postmortem deformation of
      the aorta on postmortem computed tomography (CT) by comparison with the
      antemortem CT in the same patient. MATERIALS AND METHODS: A total of 58 non
      traumatic patients without hemorrhagic events who underwent torso CT before and
      shortly after death were enrolled. Antemortem chest and abdominal CT were
      obtained in 44 cases and in 57 cases, respectively. The lengths of the major and
      minor axes of the ascending and descending thoracic aorta and the abdominal aorta
      were measured on both antemortem and postmortem CT in the same patient. To
      evaluate the shape of the aorta, the major axis-minor axis ratio (Ma-MiR) was
      calculated. Mean values of the diameters of the aorta and Ma-MiRs on postmortem
      CT were compared with those on antemortem CT using the Wilcoxon signed-rank test.
      We also evaluated the major and minor axes and Ma-MiRs on both antemortem and
      postmortem CT in two age groups: 65 years and under (n=13) and over 65 years
      (n=45). RESULTS: At each level tested, the aorta significantly shrank after death
      (p<0.001) (ascending thoracic aorta, descending thoracic aorta, and abdominal
      aorta: 38.5 mm * 33.5 mm, 28.0 mm * 25.9 mm, and 24.4 mm * 21.8 mm on antemortem
      CT, 30.0 mm * 26.2 mm, 24.4 mm * 20.7 mm, and 21.5 mm * 14.5 mm on postmortem CT,
      respectively). The postmortem Ma-MiRs significantly increased at the descending
      thoracic aorta and the abdominal aorta (p<0.001). The diameters of the aorta are
      longer in older cases at all levels on both antemortem and postmortem CT. The
      reduction rates were larger in younger cases than older cases at all levels.
      CONCLUSIONS: After death, the aorta shrunk at all levels, and became oval in
      shape in descending thoracic and abdominal aorta. The contraction was greater in
      younger cases than older cases. Investigators who interpret postmortem imaging
      should be aware of the postmortem deformation of the aorta.

PMID- 22656271
TI  - Clarithromycin enhances dasatinib-induced cell death in chronic myeloid leukemia
      cells, by inhibition of late stage autophagy.

PMID- 22656272
TI  - Uric acid concentration as a risk marker for blood pressure progression and
      incident hypertension: a Chinese cohort study.
AB  - OBJECTIVE: Little is known about serum uric acid (SUA) role for hypertension in
      the Asian countries with low cardiovascular events. We aimed to explore the
      relationship in a comprehensive Chinese cohort. METHODS: Participants in the
      Taiwanese Survey on Prevalences of Hypertension, Hyperglycemia, and
      Hyperlipidemia (TwSHHH) who were free of hypertension at baseline recruitment in
      2002 (n=3257) were evaluated for the longitudinal association between baseline
      SUA and blood pressure progression (BPP) and incident hypertension. RESULTS:
      During a mean follow-up of 5.41 years, 1119 persons (34.3%) had experienced
      progression to a higher blood pressure stage and 496 persons (15.2%) had
      developed hypertension. In multivariate analyses, the adjusted hazard ratios
      (HRs) [95% confidence intervals (CIs)] comparing the highest and lowest SUA
      quartiles were 1.78 (1.11-2.02, P for trend .004) for BPP and 1.68 (1.23-2.04, P
      for trend .028) for incident hypertension. The positively graded relationships
      between SUA concentration and blood pressure outcomes were observed in both males
      and females. More interestingly, a statistically significant trend for increasing
      risk of BPP and incident hypertension across SUA quartiles was most pronounced in
      participants with abdominal obesity. CONCLUSION: We concluded that SUA level was
      an independent predictor of blood pressure progression and incident hypertension
      in a Chinese population.

PMID- 22656273
TI  - Creep deformation of restorative resin-composites intended for bulk-fill
      placement.
AB  - OBJECTIVES: To determine the creep deformation of several "bulk-fill" resin
      composite formulations in comparison with some other types. METHODS: Six resin
      composites; four bulk-fill and two conventional were investigated. Stainless
      steel split molds (4 mm * 6 mm) were used to prepare cylindrical specimens for
      creep testing. Specimens were thoroughly irradiated with 650 mW cm(-2). A total
      of 10 specimens for each material were divided into two groups (n = 5) according
      to the storage condition; Group A stored dry at 37  degrees C for 24h and Group B
      stored in distilled water at 37  degrees C in an incubator for 24h. Each specimen
      was loaded (20 MPa) for 2h and unloaded for 2h. The strain deformation was
      recorded continuously for 4h. Statistical analysis was performed using a two-way
      ANOVA followed by one-way ANOVA and the Bonferroni post hoc test at a
      significance level of a = 0.05. RESULTS: The maximum creep strain % ranged from
      0.72% up to 1.55% for Group A and the range for Group B increased from 0.79% up
      to 1.80% due to water sorption. Also, the permanent set ranged from 0.14% up to
      0.47% for Group A and from 0.20% up to 0.59% for Group B. Dependent on the
      material and storage condition, the percentage of creep strain recovery ranged
      between 64% and 81%. Increased filler loading in the bulk-fill materials
      decreased the creep strain magnitude. SIGNIFICANCE: Creep deformation of all
      studied resin-composites increased with wet storage. The "bulk-fill" composites
      exhibited an acceptable creep deformation and within the range exhibited by other
      resin-composites.

PMID- 22656274
TI  - Sybron.

PMID- 22656275
TI  - Carlo erba strumentazione.

PMID- 22656277
TI  - Groundwater's future shines bright.

PMID- 22656279
TI  - International.

PMID- 22656278
TI  - Washington.

PMID- 22656281
TI  - States.

PMID- 22656280
TI  - Science.

PMID- 22656282
TI  - Technology.

PMID- 22656283
TI  - Industry.

PMID- 22656284
TI  - Pesticides of the future.

PMID- 22656286
TI  - Effluent guidelines for organic chemicals, plastics, and synthetic fibers.

PMID- 22656285
TI  - Indoor air pollution.

PMID- 22656287
TI  - Selected strategies to reduce acidic deposition in the U.S.

PMID- 22656289
TI  - Products.

PMID- 22656288
TI  - PCB replacements in dielectric fluid.

PMID- 22656290
TI  - Literature.

PMID- 22656292
TI  - Vaisala.

PMID- 22656291
TI  - CHEMetrics, Inc.

PMID- 22656294
TI  - Bioanalytical systems.

PMID- 22656296
TI  - International.

PMID- 22656298
TI  - Industrial & environmental analysts, inc.

PMID- 22656299
TI  - Fill a staff position on capitol hill.

PMID- 22656300
TI  - professional consulting services directory.

PMID- 22656302
TI  - Classified section.

PMID- 22656303
TI  - Iron transport-mediated drug delivery: practical syntheses and in vitro
      antibacterial studies of tris-catecholate siderophore-aminopenicillin conjugates
      reveals selectively potent antipseudomonal activity.
AB  - An artificial tris-catecolate siderophore with a tripodal backbone and its
      conjugates with ampicillin and amoxicillin were synthesized. Both conjugates
      exhibited significantly enhanced in vitro antibacterial activities against Gram
      negative species compared to the parent drugs, especially against  Pseudomonas
      aeruginosa . The conjugates appeared to be assimilated by an induced bacterial
      iron transport process as their activities were inversely related to iron
      concentration. The easily synthesized tris-catecolate siderophore has great
      potential for future development of various drug conjugates to target antibiotic
      resistant Gram-negative bacteria.

PMID- 22656304
TI  - Extreme infertility.
AB  - New germ cells and new organs open new areas in the approach to treating
      infertility.

PMID- 22656305
TI  - Germline development from human pluripotent stem cells toward disease modeling of
      infertility.
AB  - Infertility caused by the disruption or absence of germ cells (i.e., sperm or
      egg) is a major and largely incurable medical problem. In vitro disease modeling
      using normal human germline cells is required to better understand the precise
      molecular mechanisms of infertility and to develop drugs to treat this condition.
      Recent advances in the differentiation methods of embryonic stem cells (ESCs)
      provide new avenues to generate germ cells in vitro. Furthermore, the discovery
      that induced pluripotent stem cells (iPSCs) can be created from a patient's adult
      somatic cells by introducing the combinations of several transcription factors
      (e.g., OCT3/4, SOX2, KLF4, and MYC) enables us to generate new and powerful in
      vitro human disease models. In this review, we summarize recent advances in the
      development of human germ cells from in vivo and in vitro cultured ESCs/iPSCs.
      Based on these studies, we propose strategies to develop in vitro disease models
      of infertility using human ESCs/iPSCs. Then, we also discuss the challenges that
      need to be addressed to harness the full potential of these models. These models
      will enable us to understand the precise molecular pathologies of infertility and
      will aid in the development of new treatments.

PMID- 22656306
TI  - Ovarian tissue and follicle transplantation as an option for fertility
      preservation.
AB  - OBJECTIVE: To review and summarize data from the scientific literature on ovarian
      tissue and follicle transplantation as an option for fertility preservation.
      DESIGN: Review of pertinent literature. SETTING: University hospital. PATIENT(S):
      Women having undergone ovarian tissue transplantation. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Review of the literature. RESULT(S): Over the last
      decade, the field of ovarian transplantation and cryopreservation has
      significantly progressed, becoming applicable in humans. Indeed, fresh and frozen
      cortical ovarian tissue transplantations have been successfully reported
      worldwide, resulting in around 28 healthy babies. Although ovarian-tissue
      harvesting seems to be safe, the risk of reimplantation of cancer from ovarian
      cortical transplants cannot be estimated at this time. As a consequence, auto
      transplantation of ovarian tissue in women having suffered from systemic
      hematological malignancies is not recommended. In these situations,
      reimplantation of isolated ovarian follicles might represent an interesting
      option in the future. CONCLUSION(S): Although the clinical experience is limited,
      the robust results obtained open new perspectives for the management of premature
      ovarian failure resulting or not from gonadotoxic treatments.

PMID- 22656307
TI  - Can we skip weekends in GnRH antagonist cycles without compromising the final
      outcome?

PMID- 22656308
TI  - Smad7 is a transforming growth factor-beta-inducible mediator of apoptosis in
      granulosa cells.
AB  - OBJECTIVE: To determine the functional role of Smad7 in granulosa cells. DESIGN:
      Granulosa cell culture and molecular biological techniques were used to
      investigate regulation and function of Smad7. SETTING: Research laboratory.
      ANIMAL(S): C57bl/j hybrid mouse. INTERVENTION(S): Primary mouse granulosa cells
      were isolated and grown in culture for all messenger RNA expression experiments.
      Smad7 promoter constructs were evaluated with a luciferase reporter system in
      SIGC cells to determine sites activating Smad7 expression. MAIN OUTCOME
      MEASURE(S): Overexpression (Smad7 complementary DNA) and downregulation (Smad7
      small interfering RNA) of Smad7 in primary mouse granulosa cells were used to
      evaluate the functional role of Smad7 in granulosa cells. RESULT(S): Smad7
      expression was upregulated by treatment with transforming growth factor-beta (TGF
      beta) but not activin or activation of the cyclic adenosine monophosphate
      pathway. The promoter of Smad7 was activated by TGF-beta. Truncation of the
      promoter or mutation of the Smad response element at -141 eliminated TGF-beta
      activation of the promoter. Smad3 was not specifically required for TGF-beta
      stimulated expression of Smad7, though activation of the TGFBR1 receptor was.
      When Smad7 was overexpressed in granulosa cells, apoptosis was markedly
      increased. When Smad7 expression was reduced with small interfering RNA, then the
      TGF-beta-induced apoptosis was blocked. CONCLUSION(S): Smad7 mediates apoptosis
      induced by TGF-beta in mouse granulosa cells, suggesting that dysregulation of
      Smad7 could impair folliculogenesis.

PMID- 22656309
TI  - Commentary: Fear of movement/(re)injury and activity avoidance in persons with
      neurogenic versus vascular claudication: why are spinal stenosis patients scared
      stiff?

PMID- 22656310
TI  - Commentary: Hypovitaminosis D in patients undergoing kyphoplasty is associated
      with increased risk of subsequent vertebral fractures.

PMID- 22656311
TI  - Commentary: Does needle injection cause disc degeneration? News in the continuing
      debate regarding pathophysiology associated with intradiscal injections.

PMID- 22656312
TI  - Commentary: Can observational studies provide suitable evidence for spine
      interventions?

PMID- 22656314
TI  - Recommendations on ultrasound for low back pain: profit-driven or evidence-based?

PMID- 22656315
TI  - Hydrophilic versus hydrophobic porogens for engineering of poly(lactide-co
      glycolide) microparticles containing risedronate sodium.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of two
      mechanistically different porogens, namely: the hydrophilic hydroxy-propyl-beta
      cyclodextrin and the hydrophobic porogens (mineral oil and corn oil) in producing
      open/closed pored engineered polylactide-co-glycolic-acid microspheres suitable
      for pulmonary delivery of risedronate sodium (RS). MATERIALS AND METHODS: Surface
      morphology of the microspheres was studied and they were characterized for
      entrapment efficiency (%EE), particle size, and porosity as well as aerodynamic
      and flow properties. Selected formulae were investigated for in vitro drug
      release and deposition behavior using next generation impactor. Furthermore, the
      safety of the free drug and the selected prepared systems was assessed by MTT
      viability test performed on Calu-3 cell line. RESULTS AND DISCUSSION: The current
      work revealed that HP-beta-CD produced open-pored microspheres, while oils
      produced closed pored microspheres. Modulation of preparation parameters
      generated porous RS microspheres with high %EE, sustained drug release profile up
      to 15 days, suitable geometric and aerodynamic particle sizes and excellent flow
      properties. The safety of HP-beta-CD systems was higher than the systems
      utilizing oil as porogen. CONCLUSION: Porogen type affected the behavior of the
      microspheres as demonstrated by the various characterization experiments, with
      microspheres prepared using HP-beta-CD being superior to those prepared using
      oils as porogens.

PMID- 22656316
TI  - NanoTIO(2) (UV-Titan) does not induce ESTR mutations in the germline of
      prenatally exposed female mice.
AB  - BACKGROUND: Particulate air pollution has been linked to an increased risk of
      cardiovascular disease and cancer. Animal studies have shown that inhalation of
      air particulates induces mutations in the male germline. Expanded simple tandem
      repeat (ESTR) loci in mice are sensitive markers of mutagenic effects on male
      germ cells resulting from environmental exposures; however, female germ cells
      have received little attention. Oocytes may be vulnerable during stages of active
      cell division (e.g., during fetal development). Accordingly, an increase in
      germline ESTR mutations in female mice prenatally exposed to radiation has
      previously been reported. Here we investigate the effects of nanoparticles on the
      female germline. Since pulmonary exposure to nanosized titanium dioxide
      (nanoTiO(2)) produces a long-lasting inflammatory response in mice, it was chosen
      for the present study. FINDINGS: Pregnant C57BL/6 mice were exposed by whole-body
      inhalation to the nanoTiO(2) UV-Titan L181 (~42.4 mg UV-Titan/m(3)) or filtered
      clean air on gestation days (GD) 8-18. Female C57BL/6 F1 offspring were raised to
      maturity and mated with unexposed CBA males. The F2 descendents were collected
      and ESTR germline mutation rates in this generation were estimated from full
      pedigrees (mother, father, offspring) of F1 female mice (192 UV-Titan-exposed F2
      offspring and 164 F2 controls). ESTR mutation rates of 0.029 (maternal allele)
      and 0.047 (paternal allele) in UV-Titan-exposed F2 offspring were not
      statistically different from those of F2 controls: 0.037 (maternal allele) and
      0.061 (paternal allele). CONCLUSIONS: We found no evidence for increased ESTR
      mutation rates in F1 females exposed in utero to UV-Titan nanoparticles from GD8
      18 relative to control females.

PMID- 22656317
TI  - Effects of production factors and egg-bearing period on the antioxidant activity
      of enzymatic hydrolysates from shrimp (Pandalopsis dispar) processing byproducts.
AB  - The effects of production factors (protease used, percent enzyme, hydrolysis
      time, and water-to-substrate ratio) on the antioxidant activity of hydrolysates
      produced from shrimp processing byproducts (SPB) were assessed using Taguchi's
      L16 (4(5)) fractional factorial design. SPB hydrolysates showed excellent ABTS
      radical scavenging activity, metal ion chelating capacity, and inhibition of
      lipid peroxidation, but weak DPPH radical scavenging activity and ferric ion
      reducing antioxidant power. The protease used significantly influenced
      antioxidant activities while hydrolysis time and percent enzyme affected radical
      scavenging activities and inhibition of lipid peroxidation, respectively.
      Differences in the lipid and amino acid contents observed between SPB collected
      early and late in the egg-bearing period may have contributed to the slight
      variance in antioxidant activities displayed by their hydrolysates. Nevertheless,
      SPB hydrolysates produced using Alcalase or Protamex had high antioxidant
      activity regardless of production factors and egg-bearing period. 

PMID- 22656318
TI  - Gas-phase uranyl, neptunyl, and plutonyl: hydration and oxidation studied by
      experiment and theory.
AB  - The following monopositive actinyl ions were produced by electrospray ionization
      of aqueous solutions of An(VI)O(2)(ClO(4))(2) (An = U, Np, Pu): U(V)O(2)(+),
      Np(V)O(2)(+), Pu(V)O(2)(+), U(VI)O(2)(OH)(+), and Pu(VI)O(2)(OH)(+); abundances
      of the actinyl ions reflect the relative stabilities of the An(VI) and An(V)
      oxidation states. Gas-phase reactions with water in an ion trap revealed that
      water addition terminates at AnO(2)(+).(H(2)O)(4) (An = U, Np, Pu) and
      AnO(2)(OH)(+).(H(2)O)(3) (An = U, Pu), each with four equatorial ligands. These
      terminal hydrates evidently correspond to the maximum inner-sphere water
      coordination in the gas phase, as substantiated by density functional theory
      (DFT) computations of the hydrate structures and energetics. Measured hydration
      rates for the AnO(2)(OH)(+) were substantially faster than for the AnO(2)(+),
      reflecting additional vibrational degrees of freedom in the hydroxide ions for
      stabilization of hot adducts. Dioxygen addition resulted in
      UO(2)(+)(O(2))(H(2)O)(n) (n = 2, 3), whereas O(2) addition was not observed for
      NpO(2)(+) or PuO(2)(+) hydrates. DFT suggests that two-electron three-centered
      bonds form between UO(2)(+) and O(2), but not between NpO(2)(+) and O(2). As
      formation of the UO(2)(+)-O(2) bonds formally corresponds to the oxidation of
      U(V) to U(VI), the absence of this bonding with NpO(2)(+) can be considered a
      manifestation of the lower relative stability of Np(VI).

PMID- 22656319
TI  - The effect of various absorption enhancers on tight junction in the human
      intestinal Caco-2 cell line.
AB  - Present work investigates the potential of absorption enhancers (glucose, EDTA,
      sodium cholate, SDS, ethanol and menthol) to open the cellular tight junctions
      and in doing so improve the paracellular permeability of macromolecules. Initial
      work assessed cytotoxicity (through MTT assays) of absorption enhancers on Caco-2
      cells to confirm the suitable concentration and action time. Subsequently,
      macromolecular permeability across filter-cultured Caco-2 monolayers was
      detected. The six enhancers were also tested for the effect on the distribution
      of the tight junction proteins, ZO-1, claudin-1, occludin, and E-cadherin. The
      results showed that the six enhancers at certain concentration and action time
      caused little cytotoxicity to Caco-2 cells and increased the permeability of
      fluorescein isothiocyanate (FITC) and FITC-dextrans, as well as producing changes
      in ZO-1, claudin-1, occludin, and E-cadherin distribution, indicating a tight
      junction effect.

PMID- 22656320
TI  - Progressive diffuse brain atrophy in West syndrome with marked hypomyelination
      due to SPTAN1 gene mutation.
AB  - A 1-year-old male began suffering from West syndrome at 3 months of age, when
      electroencephalography revealed hypsarrhythmia accompanied by a periodic, brief
      suppression phase. The administration of adrenocorticotropic hormone was
      partially effective for stopping the condition, and the seizure type evolved into
      brief tonic seizures at 6 months. Thereafter, progressive atrophy of the brain
      became evident by 9 months of age, predominantly at the brainstem and cerebellum.
      Severe hypomyelination of the cerebral white matter was revealed at the age of 1
      year, and a de novo heterozygous mutation in the SPTAN1 gene was confirmed. The
      patient showed severely impaired psychomotor development, and had gained no
      visual attention. These findings contribute to the characterization of this
      recently established entity and facilitate the identification of further
      patients.

PMID- 22656321
TI  - Spontaneous movements in the supine position of healthy term infants and preterm
      infants with or without periventricular leukomalacia.
AB  - AIM: The individual motor elements presumed to be essential for motor development
      were determined from spontaneous movements involving the entire body of normal
      term and preterm infants. Then, diagnostic items for motor abnormality in infants
      with periventricular leukomalacia (PVL) were investigated. METHODS: Video
      recordings of 24 healthy term infants, 21 normal preterm infants (8 males, 13
      females; median gestational age 30 weeks; median birth weight 1216g) and 14
      preterm infants with PVL (6 males, 8 females; median gestational age 30 weeks;
      median birth weight 1360g) were analyzed. RESULTS: In healthy term infants,
      predominant shoulder rotation was noticed until 1 month of age. After 2 months of
      age, isolated movements of the shoulder, elbow, hip, knee, and ankle frequently
      emerged. In preterm infants with PVL at the corrected age of 2 months, startle
      response and predominant shoulder rotation were more frequently seen and isolated
      neck, shoulder, elbow, hip, knee, and ankle movements were less frequently seen
      than in the normal preterm infants (Fisher's exact test, p<0.025).
      INTERPRETATION: At 2 months of age, isolated movements evolve, and their failure
      to occur is suggested to be a useful sign for the diagnosis of cerebral motor
      disorders.

PMID- 22656323
TI  - Tailoring inputs to achieve maximal neuronal firing.
AB  - We consider the constrained optimization of excitatory synaptic input patterns
      to maximize spike generation in leaky integrate-and-fire (LIF) and theta model
      neurons. In the case of discrete input kicks with a fixed total magnitude,
      optimal input timings and strengths are identified for each model using phase
      plane arguments. In both cases, optimal features relate to finding an input level
      at which the drop in input between successive spikes is minimized. A bounded
      minimizing level always exists in the theta model and may or may not exist in the
      LIF model, depending on parameter tuning. We also provide analytical formulas to
      estimate the number of spikes resulting from a given input train. In a second
      case of continuous inputs of fixed total magnitude, we analyze the tuning of an
      input shape parameter to maximize the number of spikes occurring in a fixed time
      interval. Results are obtained using numerical solution of a variational boundary
      value problem that we derive, as well as analysis, for the theta model and using
      a combination of simulation and analysis for the LIF model. In particular,
      consistent with the discrete case, the number of spikes in the theta model rises
      and then falls again as the input becomes more tightly peaked. Under a similar
      variation in the LIF case, we numerically show that the number of spikes
      increases monotonically up to some bound and we analytically constrain the times
      at which spikes can occur and estimate the bound on the number of spikes fired.

PMID- 22656322
TI  - Total and individual antioxidant intake and risk of epithelial ovarian cancer.
AB  - BACKGROUND: Limiting oxidative stress to the ovarian epithelium has been proposed
      as a first-line defense against ovarian cancer. Although evidence for an
      association between individual dietary antioxidant intake and ovarian cancer risk
      is conflicting, the combined evidence suggests a modest inverse association. Our
      study aimed to evaluate the association between total antioxidant capacity (TAC)
      and individual antioxidant intakes (vitamin C, vitamin E, beta-carotene,
      selenium, lutein, and lycopene) and ovarian cancer risk. METHODS: We conducted a
      population-based case-control study in New Jersey. Cases were women ages 21 years
      and older with newly diagnosed epithelial ovarian cancer who resided in six
      counties of New Jersey. Controls were women in the same age range who resided in
      the same geographic area. A total of 205 ovarian cancer cases and 390 controls
      were included. Dietary intake was ascertained using the Block food frequency
      questionnaire (FFQ), and TAC indices were constructed by linking FFQ-derived
      estimates to two standardized antioxidant capacity databases, the USDA Oxygen
      Radical Absorbance Capacity (ORAC) Database, and the University of Olso's
      Antioxidant Food Database. Multivariate logistic regression models were used to
      calculate odds ratios and 95 % confidence intervals while controlling for major
      ovarian cancer risk factors. RESULTS: We found a strong inverse association with
      selenium from food sources (OR: 0.41; 95 % CI: 0.20-0.85, for the highest vs.
      lowest tertile of dietary selenium intake). However, there was little evidence of
      an association with dietary TAC or the others individual antioxidants. In
      contrast, compared to non-users, supplement users had significant increased risk
      for all micronutrients, but no statistically significant increased risk was
      observed for combined intake from foods and supplements of any of these
      antioxidants. CONCLUSIONS: This study found an inverse association between
      selenium consumption from food sources and ovarian cancer risk, while there was
      little evidence of an association with TAC or any of the other individual
      antioxidants. Additional research is needed to confirm these findings.

PMID- 22656324
TI  - Separation of cis-trans phospholipid isomers using reversed phase LC with high
      resolution MS detection.
AB  - The increased presence of synthetic trans fatty acids into western diets has been
      shown to have deleterious effects on physiology and raising an individual's risk
      of developing metabolic disease, cardiovascular disease, and stroke. The
      importance of these fatty acids for health and the diversity of their (patho)
      physiological effects suggest that not only should the free trans fatty acids be
      studied but also monitoring the presence of these fats into the side chains of
      biological lipids, such as glycerophospholipids, is also essential. We developed
      a high resolution LC-MS method that quantitatively monitors the major lipid
      classes found in biospecimens in an efficient, sensitive, and robust manner while
      also characterizing individual lipid side chains through the use of high energy
      collisional dissociation (HCD) fragmentation and chromatographic alignment. We
      herein show how this previously described reversed phase method can baseline
      separate the cis-trans isomers of phosphatidylglycerol and phosphatidylcholine
      (PC) with two 18:1 side chains, in both positive and negative mode, as neat
      solutions and when spiked into a biological matrix. Endogenous PC (18:1/18:1)-cis
      and PC (18:1/18:1)-trans isomers were examined in mitochondrial and serum
      profiling studies, where rats were fed diets enriched in either trans 18:1 fatty
      acids or cis 18:1 fatty acids. In this study, we determined the cis:trans isomer
      ratios of PC (18:1/18:1) and related this ratio to dietary composition. This
      generalized LC-MS method enables the monitoring of trans fats in biological
      lipids in the context of a nontargeted method, allowing for relative quantitation
      and enhanced identification of unknown lipids in complex matrixes.

PMID- 22656325
TI  - Modelling aluminium leaching into food from different foodware materials with
      multi-level factorial design of experiments.
AB  - To estimate the contribution of aluminium (Al) leaching from different materials
      used for food preparation and serving to the dietary Al intake, Al release from
      foodware typically used in everyday life was investigated using multilevel
      factorial design (MFD) of experiments. For Al characterisation, sample
      preparation and an analytical method using inductively coupled plasma atomic
      emission spectroscopy was developed and validated. Parameter influence
      (temperature: x1, contact time: x2, pH: x3, salt concentration: x4, viscosity:
      x5), was evaluated with analysis of variance suggesting that the influence of
      viscosity is not significant compared to the other four studied parameters.
      Therefore, predictive, exponential quadratic regression models were established
      with x1-x4. Cross-validation and a set of independent experiments in real food
      products were used to test the prediction force of the different models. They
      both suggest that the quality of the models established for Al foil, Al plate and
      ceramic ware is satisfactory, but less good for glassware and stainless steel.
      Indeed, in the studied conditions, leaching from these latter food wares was
      often close to or even below the limit of quantification suggesting that the
      principal sources of Al intake from food contact materials during food processing
      are utensils made of Al and ceramic ware.

PMID- 22656326
TI  - Synthesis and photophysical properties of an Eu(II)-complex/PS blend: role of Ag
      nanoparticles in surface-enhanced luminescence.
AB  - A novel Eu(II) complex with 2-ethylhexyl hydrogen 2-ethylhexyl phosphonate
      (EHHEHP or PC88A) was synthesized and blended with polystyrene polymer (PS). Both
      an independent complex and the Eu(II)/PS blend excited by near-UV light produced
      blue luminescence, arising from the 5d-> 4f transitions of Eu(II). Time-dependent
      density functional theory (TD-DFT) calculations on electronic structures of the
      complex molecule indicated that the absorbing and emitting center was associated
      with the (2)A(d(z(2))) state under the C(2) crystal field. We also synthesized
      silver nanoparticles (Ag NPs) with an average particle size of 4.48 nm (sigma =
      0.91 nm) using EHHEHP as a stabilizer. The effects of Ag NPs as a colloidal
      suspension and an interfacial layer on the luminescence intensity of the blend
      were investigated as functions of the concentration of Ag NPs and the thickness
      of the Ag NP layer, respectively. The critical concentration of the colloidal Ag
      NPs and the critical thickness of the interfacial Ag NP layer were ~355 ppm and
      ~0.16 MUm, respectively. Under critical conditions, the Ag NPs increased the
      luminescence intensity by 4.4 times as a colloidal suspension in CH(2)Cl(2) and
      2.2 times as an interfacial-layer state.

PMID- 22656327
TI  - Biofilm formation on abiotic and biotic surfaces during Spanish style green table
      olive fermentation.
AB  - In this work, the establishment of polymicrobial communities on the surfaces
      which come into contact with the brine during Spanish style Gordal cv. green
      olive fermentation when subjected to spontaneous or controlled processes
      (inoculated with Lactobacillus pentosus LPCO10 or 128/2) was studied. Scanning
      electron microscopy showed that L. pentosus and yeast populations were able to
      form mixed biofilms throughout the fermentation process on both abiotic (glass
      slide) and biotic (olive skin) surfaces. The biofilm architectures in both
      supports were completely different: on the glass slides only aggregates of L.
      pentosus and yeasts without any polymeric matrix surrounding them were found
      while on the skin of the fruits, true mature biofilms were observed. During
      fermentation, the lactic acid bacteria (LAB) population on the olives remained
      similar while that of yeasts increased progressively to reach similar levels at
      the end of the process (8-9 log CFU/cm(2)). Molecular analysis showed that
      different populations of L. pentosus and yeasts were the only microbial members
      of the biofilm formed during fermentation, regardless of inoculation. Hence, the
      green olive surface provides an appropriate environmental condition for the
      suitable development and formation of complex biofilms during controlled or
      natural table olive processing.

PMID- 22656328
TI  - The diagnosis and management of non-alcoholic fatty liver disease: practice
      guideline by the American Gastroenterological Association, American Association
      for the Study of Liver Diseases, and American College of Gastroenterology.

PMID- 22656329
TI  - Induction of apoptosis and inhibition of cell proliferation by the cyclooxgenase
      enzyme blocker nimesulide in the Ishikawa endometrial cancer cell line.
AB  - OBJECTIVES: Endometrial cancer remains a leading cause of death in women and
      therefore the development of new therapies is essential. The present study
      evaluated the effects of nimesulide alone, cisplatin alone, and combination of
      cisplatin and nimesulide on an Ishikawa cell line with respect to cytotoxicity
      and induction of apoptosis in vitro. STUDY DESIGN: Ishikawa cells were treated
      with increasing doses of nimesulide alone, cisplatin alone, and a combination of
      cisplatin and nimesulide. Subsequently their effects on cytotoxicity were
      investigated by MTT assay, while apoptosis was investigated by DAPI and JC-1
      staining and caspase-3 colorimetric assays. RESULTS: 3-(4,5-Dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay showed that nimesulide alone and
      combination of cisplatin and nimesulide have growth inhibitory effect on Ishikawa
      cells. Nimesulide alone and the combination of cisplatin and nimesulide induced
      apoptosis. Apoptosis induced by nimesulide might be related to caspase-3
      activation. CONCLUSIONS: These results suggest that nimesulide treatment is as
      effective as cisplatin treatment in Ishikawa cells. The combination of cisplatin
      and nimesulide treatment is more effective than cisplatin alone in Ishikawa
      cells.

PMID- 22656330
TI  - A novel modification of conventional laparoscopic myomectomy using manual
      assistance for multiple uterine myomas.
AB  - OBJECTIVES: To evaluate the efficacy and feasibility of finger-assisted
      laparoscopic myomectomy for multiple myomas. STUDY DESIGN: A total of 565
      patients with symptomatic myomas underwent finger-assisted laparoscopic
      myomectomy between January 2006 and March 2011 to remove multiple myomas at our
      center. Laparoscopic myomectomy technique was modified, and involved the
      insertion of two fingers into the vagina to elevate the uterus, while one or two
      fingers of the other hand were inserted into the abdomen through a suprapubic 15
      mm trocar port for palpation of small myomas, which did not distort the uterine
      contour. RESULTS: The mean (SD; range) patient age was 38.26 years (5.84; 25-48
      years). The diameter of the largest myoma in each case was 6.13 cm (1.21; 4-15
      cm). The total number of myomas enucleated in the initial enucleation was 2228.
      There were 597 additional myomas enucleated with finger-assisted guidance. The
      mean diameter of the additionally enucleated myomas was 1.1 cm (range, 0.2-2.5
      cm), which was significantly smaller than those of the initially enucleated
      myomas (p=0.002). The mean operative time was 97.1 min (30.2; 35-180 min). The
      decrease in postoperative hemoglobin concentration was 1.6g/dL (0.7; 0.4
      3.2g/dL). During the operation, no patients required a blood transfusion. Six
      patients developed postoperative fever. There was no occurrence of bowel or
      urinary tract injury. The mean postoperative hospital stay was 3.2 days (0.9; 2-6
      d). All procedures were successfully completed without the need for laparotomy.
      CONCLUSIONS: Finger-assisted laparoscopic myomectomy is a feasible and safe
      approach in the surgical treatment of multiple myomas.

PMID- 22656331
TI  - Fetal color-coded tissue Doppler echocardiography: experiences with the "tracking
      method" in normal fetuses.
AB  - OBJECTIVE: Ultrasound-based tissue Doppler imaging has opened new perspectives
      for non-invasive quantification of global, as well as regional, myocardial
      function. We therefore studied fetal hearts using the "tracking method" in order
      to assess its feasibility and changes of fetal myocardial velocities throughout
      gestation. STUDY DESIGN: In 89 healthy fetuses color-coded tissue Doppler
      echocardiography (TDE) was prospectively conducted for further offline-analysis
      of global and regional myocardial function of the basal segment. Maximum tissue
      velocities at systole (S), in the early filling phase of diastole (E) and during
      atrial contraction (A) were estimated from three consecutive cardiac cycles.
      RESULTS: Within a selected time limit of 15 min, raw data acquisition was
      possible in 60 of the 89 fetuses (67%). From the stored samples, velocities of S,
      E and A-wave could be obtained in 76% with good reproducibility for septal and
      right wall velocities. During gestation all velocities increased but to a greater
      extent at the right and left ventricular wall compared to the interventricular
      septum. The A-wave velocity was higher than E-wave velocity in all basal
      segments. Throughout gestation, the increase in E-wave was higher, resulting in
      an increase of the E-wave/A-wave ratio. CONCLUSION: Tissue Doppler
      echocardiography using the tracking method in fetal hearts is practical during
      routine clinical examination, but it is time consuming and requires highly
      experienced observers The knowledge of myocardial velocities in normal
      pregnancies is essential in detecting pathologies.

PMID- 22656333
TI  - Shaping cities for health: a UCL/Lancet Commission.

PMID- 22656332
TI  - Conformational basis for asymmetric seeding barrier in filaments of three- and
      four-repeat tau.
AB  - Tau pathology in Alzheimer's disease is intimately linked to the deposition of
      proteinacious filaments, which akin to infectious prions, have been proposed to
      spread via seeded conversion. Here we use double electron-electron resonance
      (DEER) spectroscopy in combination with extensive computational analysis to show
      that filaments of three- (3R) and four-repeat (4R) tau are conformationally
      distinct. Distance measurements between spin labels in the third repeat, reveal
      tau amyloid filaments as ensembles of known beta-strand-turn-beta-strand U-turn
      motifs. Whereas filaments seeded with 3R tau are structurally homogeneous,
      filaments seeded with 4R tau are heterogeneous, composed of at least three
      distinct conformers. These findings establish a molecular basis for the seeding
      barrier between different tau isoforms and offer a new powerful approach for
      investigating the composition and dynamics of amyloid fibril ensembles.

PMID- 22656334
TI  - Zinc treatment for serious infections in young infants.

PMID- 22656336
TI  - Finnigan MAT Institute.

PMID- 22656338
TI  - Courses.

PMID- 22656339
TI  - Baseball shirts & chemist-tees.

PMID- 22656335
TI  - Zinc as adjunct treatment in infants aged between 7 and 120 days with probable
      serious bacterial infection: a randomised, double-blind, placebo-controlled
      trial.
AB  - BACKGROUND: Serious bacterial infections are a major cause of death in early
      infancy in developing countries. Inexpensive and accessible interventions that
      can add to the effect of standard antibiotic treatment could reduce infant
      mortality. We measured the effect of zinc as an adjunct to antibiotics in infants
      with probable serious bacterial infection. METHODS: In this randomised, double
      blind, placebo-controlled trial, we enrolled infants aged 7-120 days with
      probable serious bacterial infection at three hospitals in New Delhi, India,
      between July 6, 2005, and Dec 3, 2008. With computer-generated sequences, we
      randomly assigned infants in permuted blocks of six, stratified by whether
      patients were underweight or had diarrhoea at enrolment, to receive either 10 mg
      of zinc or placebo orally every day in addition to standard antibiotic treatment.
      The primary outcome was treatment failure, which was defined as a need to change
      antibiotics within 7 days of randomisation, or a need for intensive care, or
      death at any time within 21 days. Participants and investigators were masked to
      treatment allocation. All analyses were done by intention-to-treat. This trial is
      registered with ClinicalTrials.gov, number NCT00347386. FINDINGS: 352 infants
      were randomly assigned to receive zinc and 348 to placebo. 332 given zinc and 323
      given placebo could be assessed for treatment failure. Significantly fewer
      treatment failures occurred in the zinc group (34 [10%]) than in the placebo
      group (55 [17%]; relative risk reduction 40%, 95% CI 10-60, p=0.0113; absolute
      risk reduction 6.8%, 1.5-12.0, p=0.0111). Treatment of 15 (95% CI eight to 67)
      infants with zinc would prevent one treatment failure. Ten infants receiving zinc
      died compared with 17 given placebo (relative risk 0.57, 0.27-1.23, p=0.15).
      INTERPRETATION: Zinc could be given as adjunct treatment to reduce the risk of
      treatment failure in infants aged 7-120 days with probable serious bacterial
      infection. FUNDING: Department of Biotechnology, Government of India; the
      European Commission; the Meltzer Foundation; and the Research Council of Norway.

PMID- 22656340
TI  - International.

PMID- 22656342
TI  - Classified section * positions open.

PMID- 22656344
TI  - professional consulting services directory.

PMID- 22656345
TI  - A New ACS Audio Course.

PMID- 22656346
TI  - Wiley-interscience.

PMID- 22656347
TI  - An expanding experien.

PMID- 22656349
TI  - Author's response.

PMID- 22656350
TI  - Wildlife toxicology.

PMID- 22656352
TI  - Combating environmental hysteria-An ACS responsibility.

PMID- 22656351
TI  - Water chemicals-hypochlorite.

PMID- 22656353
TI  - Pact.

PMID- 22656354
TI  - Washington.

PMID- 22656355
TI  - States.

PMID- 22656356
TI  - Technology.

PMID- 22656357
TI  - Science.

PMID- 22656359
TI  - Trying to track down a chemistry professor?

PMID- 22656358
TI  - Industry.

PMID- 22656360
TI  - Water research needs and trends.

PMID- 22656361
TI  - Enforcement by EPA.

PMID- 22656362
TI  - Renewable energy.

PMID- 22656363
TI  - Unusual hydrocarbons: syntheses & properties.

PMID- 22656364
TI  - Environmental agenda for the new Congress.

PMID- 22656365
TI  - Environmental data display.

PMID- 22656366
TI  - Air monitoring: Research needs.

PMID- 22656367
TI  - Products.

PMID- 22656368
TI  - Literature.

PMID- 22656369
TI  - Clinical findings and treatment in cattle with caecal dilatation.
AB  - BACKGROUND: This retrospective study describes the clinical and laboratory
      findings, treatment and outcome of 461 cattle with caecal dilatation. RESULTS:
      The general condition and demeanor were abnormal in 93.1% of cases, and 32.1% of
      the patients had colic. Ruminal motility was reduced or absent in 78.3% of
      cattle. In 82.6% of cases, swinging and/or percussion auscultation were positive
      on the right side, and 82.4% had little or no faeces in the rectum. Caecal
      dilatation could be diagnosed via rectal palpation in 405 (88.0%) cattle. There
      was caudal displacement of the dilated caecum in 291 patients, torsion around the
      longitudinal axis in 20 and retroflexion in 94. The most important laboratory
      finding was hypocalcaemia, which occurred in 85.1% of cases. Of the 461 cattle,
      122 (26.5%) initially received conservative therapy (intravenous fluids,
      neostigmine, calcium borogluconate) and 329 (71.4%) underwent surgical treatment.
      Ten patients were slaughtered or euthanased after the initial physical
      examination. Of the 122 cattle that received conservative treatment, 42 did not
      respond after one to two days of therapy and required surgical treatment. The
      final number of cattle that were operated was 371 (80.5%). Because of a grave
      prognosis, 24 cases were euthanased or slaughtered intraoperatively. Another 24
      cattle did not respond to one or more operations and were euthanased or
      slaughtered. Of the 461 patients, 403 (87.4%) responded to either conservative or
      surgical treatment and were cured, and 58 were euthanased or slaughtered.
      CONCLUSIONS: Caecal dilatation can usually be diagnosed based on clinical
      findings and treated conservatively or surgically. Swinging and percussion
      auscultation as well as rectal examination are important diagnostic tools.
      Conservative treatment is not rewarding in cattle considered surgical candidates
      with suspected caecal torsion or retroflexion and surgery should not be delayed
      in these patients.

PMID- 22656370
TI  - Thermodynamics of axial substitution and kinetics of reactions with amino acids
      for the paddlewheel complex tetrakis(acetato)chloridodiruthenium(II,III).
AB  - The known paddlewheel, tetrakis(acetato)chloridodiruthenium(II,III), offers a
      versatile synthetic route to a novel class of antitumor diruthenium(II,III)
      metallo drugs, where the equatorial ligands are nonsteroidal anti-inflammatory
      carboxylates. This complex was studied here as a soluble starting prototype model
      for antitumor analogues to elucidate the reactivity of the
      [Ru(2)(CH(3)COO)(4)](+) framework. Thermodynamic studies on equilibration
      reactions for axial substitution of water by chloride and kinetic studies on
      reactions of the diaqua complexes with the amino acids glycine, cysteine,
      histidine, and tryptophan were performed. The standard thermodynamic reaction
      parameters DeltaH degrees , DeltaS degrees , and DeltaV degrees  were determined
      and showed that both of the sequential axial substitution reactions are enthalpy
      driven. Kinetic rate laws and rate constants were determined for the axial
      substitution reactions of coordinated water by the amino acids that gave the
      corresponding aqua(amino acid)-Ru(2) substituted species. The results revealed
      that the [Ru(2)(CH(3)COO)(4)](+) paddlewheel framework remained stable during the
      axial ligand substitution reactions and was also mostly preserved in the presence
      of the amino acids.

PMID- 22656371
TI  - Fundamentals of nutrigenetics and nutrigenomics.
AB  - This volume of Progress in Molecular Biology and Translational Science is devoted
      to the exciting and promising field of nutrigenetics and nutrigenomics. The
      introductory chapter defines the basic concepts necessary for the interpretation
      of the material covered in the remainder of the volume. Emphasis is on the
      concept of personalized nutrition and its likely role in public health and
      disease prevention, as well as in therapeutics. Nutrigenetics refers to the role
      of DNA sequence variation in the responses to nutrients, whereas nutrigenomics is
      the study of the role of nutrients in gene expression. This research is
      predicated on the assumption that there are individual differences in
      responsiveness to acute or repeated exposures to a given nutrient or combination
      of nutrients. Throughout human history, diet has affected the expression of
      genes, resulting in phenotypes that are able to successfully respond to
      environmental challenges and that allow better exploitation of food resources.
      These adaptations have been key to human growth and development. Technological
      advances have made it possible to investigate not only specific genes but also to
      explore in unbiased designs the whole genome-wide complement of DNA sequence
      variants or transcriptome. These advances provide an opportunity to establish the
      foundation for incorporating biological individuality into dietary
      recommendations, with significant therapeutic potential.

PMID- 22656372
TI  - Advances in technologies and study design.
AB  - The initial draft sequence of the human genome was the proving ground for
      significant technological advancements, and its completion has ushered in
      increasingly sophisticated tools and ever-increasing amounts of data. Often, this
      combination has multiplicative effects such as stimulating research groups to
      consider subsequent experiments of at least equal if not greater complexity or
      employ advanced technologies. As applied to the fields of nutrigenetics and
      nutrigenomics, these advances in technology and experimental design allow
      researchers to probe the biological, biochemical, and physiological mechanisms
      underpinning the response to micro- and macronutrients, along with downstream
      health effects. It is becoming ever more apparent that effects on gene expression
      as a consequence of genetic variation and perturbations to cellular and
      physiological systems are an important cornerstone of nutrigenomics and
      nutrigenetics research. A critical, near-term objective, however, must be to
      determine where and how nutrients and their metabolites augment or disrupt the
      genetic variation-gene expression axis. Downstream effects on protein and
      metabolite measures are also seen with growing regularity as vital components to
      this research. Thus, this chapter reviews the scope of recent progress and
      innovation in genomics and associated technologies as well as study designs as
      applied to nutrigenomics and nutrigenetics research and provides concrete
      examples of the application of those advancements in genomics-oriented nutrition
      research.

PMID- 22656373
TI  - A nutrigenomics view of protein intake: macronutrient, bioactive peptides, and
      protein turnover.
AB  - Proteins are needed for the development and sustainability of life. They are the
      molecular machines and building blocks in the human body that drive or exert most
      biological functions and confer structure and function to cell and tissue
      architecture. Dietary proteins provide essential amino acids and complement lipid
      and carbohydrate as a major source of energy. Therefore, humans must consume a
      sufficient amount and quality of proteins to stay healthy and avoid deficiencies.
      Even with a reasonable amount of intake, variability in protein consumption can
      result in measurable health consequences in specific conditions. This said,
      dietary protein delivers more than energy and building blocks to the human body:
      the pools of body, tissue, and cell proteins, peptides, and amino acids are under
      complex metabolic control, resulting in a highly dynamic protein turnover, that
      is, the interplay between synthesis and degradation. Proteins also contain
      peptide sequences that can be interpreted as bioactive precursors which can be
      liberated upon digestion to exert biological functions locally (e.g., in the gut)
      or systemically (i.e., via the bloodstream). In this chapter, we will first
      review holistic readouts of protein intake assessed by omics technologies such as
      gene expression, proteomics, and metabolite profiling. Second, we will look at
      protein benefits beyond macronutrient supply and describe how to generate,
      analyze, and leverage bioactive peptides. In the third part, we will discuss
      protein turnover as tackled by proteomics tools that allow single-protein
      resolution at proteome-wide scale.

PMID- 22656374
TI  - Nutrigenomics and nutrigenetics of omega3 polyunsaturated fatty acids.
AB  - Diets rich in omega3 polyunsaturated fatty acids (omega3-PUFAs) such as alpha
      linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid are associated
      with decreased incidence and severity of several chronic diseases including
      cardiovascular disease (CVD) and cancer. At least some of the beneficial effects
      of these dietary fatty acids are via metabolites such as prostaglandins,
      leukotrienes, thromboxanes, and resolvins. The effects of omega3-PUFAs are in
      contrast to those of fatty acids with virtually identical structures, such as the
      omega6-PUFAs linoleic acid and arachidonic acid, and their corresponding
      metabolites. The purpose of this chapter is to discuss both the nutrigenomics
      (nutrient-gene interactions) and nutrigenetics (genetic variation in nutrition)
      of dietary fatty acids with a focus on the omega3-PUFAs (Gebauer et al.,
      2007(1)). Important in the biological response for these fatty acids or their
      metabolites are cognate receptors that are able to regulate gene expression and
      coordinately affect metabolic or signaling pathways associated with CVD and
      cancer. Four nuclear receptor (NR) subfamilies will be emphasized as receptors
      that respond to dietary and endogenous ligands: (1) peroxisome proliferator
      activated receptors, (2) retinoid X receptors, (3) liver X receptors, and (4)
      farnesoid X receptor. In addition to the different responses elicited by varying
      structures of fatty acids, responses may vary because of genetic variation in
      enzymes that metabolize omega3- and omega6 fatty acids or that respond to them.
      In particular, polymorphisms in the fatty acid desaturases and the aforementioned
      NRs contribute to the complexity of nutritional effects seen with omega3-PUFAs.
      Following a brief introduction to the health benefits of omega3-PUFAs, the
      regulation of gene expression by these dietary fatty acids via NRs will be
      characterized. Subsequently, the effects of single-nucleotide polymorphisms
      (SNPs) in key enzymes involved in the metabolism and response to omega3-PUFAs
      will be described. An outline of the events to be explored is shown in Fig. 1.
      Understanding the nutrigenomics and nutrigenetics of dietary fatty acids is key
      to understanding the etiology, as well as prevention, of critically important
      human diseases including CVD and cancer.

PMID- 22656375
TI  - Carbohydrate intake.
AB  - Carbohydrates represent more than 50% of the energy sources present in most human
      diets. Sugar intake is regulated by metabolic, neuronal, and hedonic factors, and
      gene polymorphisms are involved in determining sugar preference. Nutrigenomic
      adaptations to carbohydrate availability have been evidenced in metabolic
      diseases, in the persistence of lactose digestion, and in amylase gene copy
      number. Furthermore, dietary oligosaccharides, fermentable by gut flora, can
      modulate the microbiotal diversity to the benefit of the host. Genetic diseases
      linked to mutations in the disaccharidase genes (sucrase-isomaltase, lactase) and
      in sugar transporter genes (sodium/glucose cotransporter 1, glucose transporters
      1 and 2) severely impact carbohydrate intake. These diseases are revealed upon
      exposure to food containing the offending sugar, and withdrawal of this sugar
      from the diet prevents disease symptoms, failure to thrive, and premature death.
      Tailoring the sugar composition of diets to optimize wellness and to prevent the
      chronic occurrence of metabolic diseases is a future goal that may yet be
      realized through continued development of nutrigenetics and nutrigenomics
      approaches.

PMID- 22656377
TI  - The nutrigenetics and nutrigenomics of the dietary requirement for choline.
AB  - Advances in nutrigenetics and nutrigenomics have been instrumental in
      demonstrating that nutrient requirements vary among individuals. This is
      exemplified by studies of the nutrient choline, in which gender, single
      nucleotide polymorphisms, estrogen status, and gut microbiome composition have
      been shown to influence its optimal intake level. Choline is an essential
      nutrient with a wide range of biological functions, and current studies are aimed
      at refining our understanding of its requirements and, importantly, on defining
      the molecular mechanisms that mediate its effects in instances of suboptimal
      dietary intake. This chapter introduces the reader to challenges in developing
      individual nutrition recommendations, the biological function of choline, current
      and future research paradigms to fully understand the consequences of inadequate
      choline nutrition, and some forward thinking about the potential for
      individualized nutrition recommendations to become a tangible application for
      improved health.

PMID- 22656378
TI  - Genetic determinants of dietary antioxidant status.
AB  - Oxidative stress refers to a physiological state in which an imbalance between
      pro-oxidants and antioxidants results in oxidative damage. Oxidative stress has
      been associated with the development of numerous chronic diseases such as type 2
      diabetes, cardiovascular disease (CVD), osteoporosis, and cancer. Endogenous
      production of free radicals occurs during normal physiological processes, such as
      aerobic metabolism, oxidation of biological molecules, and enzymatic activity.
      Environmental factors such as ultraviolet radiation, air pollution, and cigarette
      smoking can also contribute to the accumulation of free radicals in the body.
      Excess free radicals can damage tissues and promote the upregulation of disease
      related pathways such as inflammation. Modulating oxidative stress by dietary
      supplementation with antioxidant micronutrients such as vitamins C and E or
      phytochemicals such as different carotenoids may help prevent or delay the
      development of certain diseases. However, research on antioxidant supplementation
      and disease has yielded inconsistent findings, which may be due, in part, to
      interindividual genetic variation. Polymorphisms in genes coding for endogenous
      antioxidant enzymes or proteins responsible for the absorption, transport,
      distribution, or metabolism of dietary antioxidants have been shown to affect
      antioxidant status and response to supplementation. These genetic variants may
      also interact with environmental factors, such as diet, to determine an
      individual's overall antioxidant status. This chapter examines current knowledge
      of the relationship between genetic variation and dietary antioxidant status.

PMID- 22656379
TI  - Mineral intake.
AB  - Minerals play a key role in the regulation of metabolic and physiological
      pathways. Adequate intake is required to maintain homeostasis, cell protection,
      functionality, and health, while deficiencies are associated with specific
      illnesses. Among the minerals, calcium, copper, iron, selenium, and zinc are
      considered especially important because of their physiological roles and their
      participation in a variety of biological processes. Also, these elements are
      associated with genetic diseases and are known to interact with genetic variants
      in a wide range of diseases.

PMID- 22656376
TI  - Genetic and epigenomic footprints of folate.
AB  - Dietary micronutrient composition has long been recognized as a determining
      factor for human health. Historically, biochemical research has successfully
      unraveled how vitamins serve as essential cofactors for enzymatic reactions in
      the biochemical machinery of the cell. Folate, also known as vitamin B9, follows
      this paradigm as well. Folate deficiency is linked to adverse health conditions,
      and dietary supplementation with folate has proven highly beneficial in the
      prevention of neural tube defects. With its function in single-carbon metabolism,
      folate levels affect nucleotide synthesis, with implications for cell
      proliferation, DNA repair, and genomic stability. Furthermore, by providing the
      single-carbon moiety in the synthesis pathway for S-adenosylmethionine, the main
      methyl donor in the cell, folate also impacts methylation reactions. It is this
      capacity that extends the reach of folate functions into the realm of epigenetics
      and gene regulation. Methylation reactions play a major role for several
      modalities of the epigenome. The specific methylation status of histones,
      noncoding RNAs, transcription factors, or DNA represents a significant
      determinant for the transcriptional output of a cell. Proper folate status is
      therefore necessary for a broad range of biological functions that go beyond the
      biochemistry of folate. In this review, we examine evolutionary, genetic, and
      epigenomic footprints of folate and the implications for human health.

PMID- 22656380
TI  - Gene-sodium interaction and blood pressure: findings from genomics research of
      blood pressure salt sensitivity.
AB  - High blood pressure (BP) is a complex trait determined by both genetic and
      environmental factors, as well as the interactions between these factors. Over
      the past few decades, there has been substantial progress in elucidating the
      genetic determinants underlying the BP response to sodium intake, or BP salt
      sensitivity. Research of monogenic BP disorders has highlighted the importance of
      renal salt handling in BP regulation, implicating genes and biological pathways
      related to salt sensitivity. Candidate gene studies have contributed important
      information toward understanding the genomic mechanisms underlying the BP
      response to salt intake, identifying genes in the renin-angiotensin-aldosterone
      system, renal sodium channels/transporters, and the endothelial system related to
      this phenotype. Despite these advancements, genome-wide association studies are
      still needed to uncover novel mechanisms underlying salt sensitivity, while
      future sequencing efforts promise the discovery of functional variants related to
      this complex trait. Delineating the genetic architecture of salt sensitivity will
      be critical to understanding how genes and dietary sodium interact to influence
      BP.

PMID- 22656381
TI  - Alcohol intake.
AB  - Alcohol consumption and its association with health or illness states are of
      great interest from the nutritional genomics point of view. This interest is
      centered not only on investigating the genetic variants that can modulate the
      effects of alcoholic beverages on different intermediate and final disease
      phenotypes (mainly cardiovascular diseases and cancer), but also on finding out
      how the genome influences the amount of alcohol consumed and consumption habits.
      This chapter reviews the latest findings on alcohol consumption trends, the
      methodological limitations in the analysis of alcohol consumption, and the main
      genes and polymorphisms related to alcohol intake, including the inconsistent
      results from genome-wide association studies (GWASs). It also reviews the effects
      of alcohol consumption on cardiovascular diseases and cancer and the studies
      analyzing the interactions between different genetic polymorphisms and alcohol in
      phenotypes related to these diseases, discussing the studies' advantages and
      limitations as well as future research perspectives.

PMID- 22656382
TI  - Coffee intake.
AB  - Coffee is one of the most widely consumed beverages in the world. Its widespread
      popularity and availability has fostered public health concerns of the potential
      health consequences of regular coffee consumption. Epidemiological studies of
      coffee intake and certain health outcomes have been inconsistent. The precise
      component of coffee potentially contributing to development of these conditions
      also remains unclear. One step toward addressing the challenges in studying the
      impact coffee has on health is a better understanding of the factors contributing
      to its consumption and physiological effects. This chapter focuses on those
      factors that are genetically determined and briefly summarizes progress in
      applying this knowledge to epidemiological studies of coffee and disease.

PMID- 22656383
TI  - Nutrigenetics and nutrigenomics of caloric restriction.
AB  - Obesity is a complex disease resulting from a chronic and long-term positive
      energy balance in which both genetic and environmental factors are involved.
      Weight-reduction methods are mainly focused on dietary changes and increased
      physical activity. However, responses to nutritional intervention programs show a
      wide range of interindividual variation, which is importantly influenced by
      genetic determinants. In this sense, subjects carrying several obesity-related
      single-nucleotide polymorphisms (SNPs) show differences in the response to
      calorie-restriction programs. Furthermore, there is evidence indicating that
      dietary components not only fuel the body but also participate in the modulation
      of gene expression. Thus, the expression pattern and nutritional regulation of
      several obesity-related genes have been studied, as well as those that are
      differentially expressed by caloric restriction. The responses to caloric
      restriction linked to the presence of SNPs in obesity-related genes are reviewed
      in this chapter. Also, the influence of energy restriction on gene expression
      pattern in different tissues is addressed.

PMID- 22656384
TI  - Individualized weight management: what can be learned from nutrigenomics and
      nutrigenetics?
AB  - The rise in the prevalence of obesity observed over the past decades is taken by
      many as an indication of the predominance of environmental factors (the so-called
      obesogenic environment) over genetic factors in explaining why obesity has
      reached epidemic proportions. While a changing environment favoring increased
      food intake and decreased physical activity levels has clearly contributed to
      shifting the distribution of body mass index (BMI) at the population level, not
      everyone is becoming overweight or obese. This suggests that there are genetic
      factors interacting with environmental factors to predispose some individuals to
      obesity. This gene-environment interaction is not only important in determining
      an individual's susceptibility to obesity but can also influence the outcome of
      weight-loss programs and weight-management strategies in overweight and obese
      subjects. This chapter reviews the role of gene-nutrient interactions in the
      context of weight management. The first section reviews the application of
      transcriptomics in human nutrition intervention studies on the molecular impact
      of caloric restriction and macronutrient composition. The second section reviews
      the effects of various obesity candidate gene polymorphisms on the response of
      body weight or weight-related phenotypes to weight-loss programs which include
      nutritional interventions.

PMID- 22656385
TI  - Taste preferences.
AB  - Personal experience, learned eating behaviors, hormones, neurotransmitters, and
      genetic variations affect food consumption. The decision of what to eat is
      modulated by taste, olfaction, and oral textural perception. Taste, in
      particular, has an important input into food preference, permitting individuals
      to differentiate nutritive and harmful substances and to select nutrients. To be
      perceived as taste, gustatory stimuli have to contact specialized receptors and
      channels expressed in taste buds in the oral cavity. Gustatory information is
      then conveyed via afferent nerves to the central nervous system, which processes
      the gustatory information at different levels, resulting in stimulus recognition,
      integration with metabolic needs, and control of ingestive reflexes. This review
      discusses physiological factors influencing the decision of what to eat, spanning
      the bow from the recognition of the nutritive value of food in the oral cavity,
      over the feedback received after ingestion, to processing of gustatory
      information to the central nervous system.

PMID- 22656386
TI  - Nutrition and the epigenome.
AB  - Epigenetic regulation is central to genome structure and function. Epigenetic
      status varies between individuals, and there is increasing awareness of the
      importance of this variation in health and disease. Epigenetic mechanisms include
      DNA methylation, histone modification, and regulation by noncoding RNAs.
      Epigenetic control is central to the way in which the genome interacts with, and
      responds to, the environment and even potentially the way in which the genome can
      influence its own environment via effects on behavior. The substrates for
      epigenetic reactions (acetyl and methyl groups) are central to nutritional
      metabolism, and there is ample evidence for nutritional effects on the epigenome.
      Challenges in human nutritional epigenetics research include the problem of
      tissue-specific epigenomes and heterogeneity of response by epigenetic loci. The
      promise of nutritional epigenetics is that it will help elucidate the way in
      which nutrition can influence health through direct effects on the genome.

PMID- 22656387
TI  - Gene-exercise interactions.
AB  - A growing body of evidence indicates that genotype-by-physical activity
      interactions on various health-related outcomes do exist. Observational studies
      have shown that relationships between DNA sequence variants and risk factors are
      significantly different between sedentary and physically active individuals,
      while exercise intervention studies have demonstrated that genetic variation
      contributes significantly to interindividual variation in responsiveness to
      exercise training. The knowledge base on gene-activity interactions will grow
      considerably within a few years when large observational genome-wide association
      study (GWAS) consortia will report their findings. Progress with exercise
      intervention studies will be slower because of resource requirements. However,
      such studies are desperately needed to fully understand the genetics as well as
      the exercise biology of complex traits and to confirm the gene-exercise
      interactions derived from observational studies. Furthermore, development of
      personalized exercise medicine applications will be difficult or even impossible
      without a proper understanding of gene-exercise interactions.

PMID- 22656388
TI  - Adaptive genetic variation and population differences.
AB  - Since the expansion of modern humans (Homo sapiens) from Africa to the rest of
      the world between 50,000 and 100,000 years ago, the human genome has been shaped
      not only by demographic history but also by adaptation to local environments,
      including regional climate, landscape, food sources, culture, and pathogens.
      Genetic differences among populations interact with environmental factors, such
      as diet and lifestyle, leading to differences in nutrient metabolism, which
      translate into differences in susceptibility to a variety of diseases.
      Individuals from different populations sharing the same environments can exhibit
      differences in disease risk, as do individuals from the same population living in
      various regions of the globe. Therefore, it is important to understand how
      adaptive genetic variations interact with environments to influence health. This
      knowledge will provide a broad foundation for designing experiments and
      approaches in nutrigenomics research and strengthening the knowledge base for
      dietary recommendations for disease prevention. The objectives of this chapter
      are to (1) understand the methodology employed in examining adaptive genetic
      variation across populations, (2) establish the importance of adaptive genetic
      variation to human health, and (3) discuss the implications for nutrigenomics
      research and disease prevention.

PMID- 22656389
TI  - Preface. Advances in nutrigenetics and nutrigenomics.

PMID- 22656390
TI  - Thermal damage patterns of diode hair-removal lasers according to various skin
      types and hair densities and colors: a simulation study.
AB  - BACKGROUND AND OBJECTIVE: It is important to prevent unwanted side effects of
      diode hair-removal lasers especially in dark skin tones. This study simulates the
      thermal damage patterns caused by diode hair-removal lasers in different skin
      types, hair colors, and hair densities. MATERIALS AND METHODS: LITCIT software
      has been used with the tissue modeled as two components, the skin and the hair.
      The absorption coefficients of various skin types (f(mel)=5%, 10%, 15%, and 20%),
      laser parameters, and optothermal properties of tissue were inputs. RESULTS: For
      all skin types there was a significant unwanted thermal damage to the epidermis
      as a result of fluence increase. Using longer pulse durations is accompanied by
      effective thermal damage to the hair follicle, while preserving the epidermis in
      skin types II and III, an effect not achieved in darker skins. Regardless of
      pulse duration, when the distance between hair follicles is <= 0.5 mm, there is a
      significant increase in thermal damage to interfollicular epidermis with high
      fluences compared with lower hair densities (interfollicular space >= 1 mm). In
      lighter hairs, while using longer pulse durations, higher fluences are needed in
      order to obtain the same level of thermal damage in the hair follicle as shorter
      pulse widths. CONCLUSIONS: In lighter skin types, lengthening the pulse duration
      of diode lasers (up to 400 ms) increases efficacy while preserving epidermis from
      unwanted thermal damage. However, it is necessary to use lower fluences while
      using longer pulse duration to avoid irreversible thermal damage to epidermis in
      darker tones, as is also true for locations with higher hair densities.

PMID- 22656392
TI  - Recent global endeavors in the detection and prevention of drug-induced liver
      injury.

PMID- 22656393
TI  - Neonatal seizures: dialogues between clinic and bench.
AB  - Neonatal seizures are common and often reflect a severe underlying neurologic
      dysfunction in neonates. Phenobarbital remains the mainstay of treatment of
      neonatal seizures, however, but it is ineffective in many patients and has
      adverse profiles in cognition. Furthermore, gamma-aminobutyric acid is excitatory
      early in brain development; therefore, treatment of neonatal seizures with
      phenobarbital must be cautious. In this review, we highlight the substantial
      progress that has been made in animal studies, and translate these results to the
      treatment of seizures in human neonates.

PMID- 22656391
TI  - Effect on skin hydration of using baby wipes to clean the napkin area of newborn
      babies: assessor-blinded randomised controlled equivalence trial.
AB  - BACKGROUND: Some national guidelines recommend the use of water alone for napkin
      cleansing. Yet, there is a readiness, amongst many parents, to use baby wipes.
      Evidence from randomised controlled trials, of the effect of baby wipes on
      newborn skin integrity is lacking. We conducted a study to examine the hypothesis
      that the use of a specifically formulated cleansing wipe on the napkin area of
      newborn infants (<1 month) has an equivalent effect on skin hydration when
      compared with using cotton wool and water (usual care). METHODS: A prospective,
      assessor-blinded, randomised controlled equivalence trial was conducted during
      2010. Healthy, term babies (n=280), recruited within 48 hours of birth, were
      randomly assigned to have their napkin area cleansed with an alcohol-free baby
      wipe (140 babies) or cotton wool and water (140 babies). Primary outcome was
      change in hydration from within 48 hours of birth to 4 weeks post-birth.
      Secondary outcomes comprised changes in trans-epidermal water loss, skin surface
      pH and erythema, presence of microbial skin contaminants/irritants at 4 weeks and
      napkin dermatitis reported by midwife at 4 weeks and mother during the 4 weeks.
      RESULTS: Complete hydration data were obtained for 254 (90.7 %) babies. Wipes
      were shown to be equivalent to water and cotton wool in terms of skin hydration
      (intention-to-treat analysis: wipes 65.4 (SD 12.4) vs. water 63.5 (14.2), p=0.47,
      95% CI -2.5 to 4.2; per protocol analysis: wipes 64.6 (12.4) vs. water 63.6
      (14.3), p=0.53, 95% CI -2.4 to 4.2). No significant differences were found in the
      secondary outcomes, except for maternal-reported napkin dermatitis, which was
      higher in the water group (p=0.025 for complete responses). CONCLUSIONS: Baby
      wipes had an equivalent effect on skin hydration when compared with cotton wool
      and water. We found no evidence of any adverse effects of using these wipes.
      These findings offer reassurance to parents who choose to use baby wipes and to
      health professionals who support their use. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN86207019.

PMID- 22656394
TI  - Age-changed normative auditory event-related potential value in children in
      Taiwan.
AB  - BACKGROUND/PURPOSE: Event-related potentials (ERPs) reflect higher cortical
      function and the P3 (P300) wave has been associated with various sensory,
      cognitive, and attention processes. The aims of this study were to understand the
      age-related change in ERPs in children between the ages of 6 and 13 years and to
      establish a normal reference value for Taiwanese children for use in future study
      of neurocognitive dysfunction in children. METHODS: Using an auditory oddball
      paradigm, ERPs were recorded in 63 mentally and physically normal children ages 6
      to 13 years. Parietal, central, and frontal ERP long-latency components (N1, P2,
      N2, P3) were measured in each test participant. RESULTS: Linear regression
      analysis demonstrated a significant linear decrease in P3, P2, N2, and N1
      latencies and a significant linear increase in P3, P2, and N1 amplitudes in
      children between the ages of 6 and 13 years. P3 latency was significantly longer
      in children ages 6-7 years than in older children. The parietal P3 latency
      decreases 6.7 msec per year from ages 6 to 13 years. A wide variation in P3
      latency in the children ages 6-7 years and a significant increase in P3 amplitude
      in those ages 12-13 years were observed from our data. A significant increase in
      P2 amplitude was also observed in children older than 10 years. CONCLUSION: The
      authors conclude that there exists an age-related change in ERP latency and
      amplitude during childhood. A negative correlation between ERP latencies and age
      and a positive correlation between ERP amplitude and age were found in this
      study. The authors emphasize that the auditory ERP value in children is not equal
      to that of adults. A normative auditory ERP value in children should be
      established prior to clinical application.

PMID- 22656395
TI  - Efficacy of intrathecal drug delivery system for refractory cancer pain patients:
      a single tertiary medical center experience.
AB  - BACKGROUND/PURPOSE: Between 10% and 20% of cancer pain patients fail to obtain
      adequate pain relief despite comprehensive medical management. The totally
      implantable programmable intrathecal drug delivery system (IDDS) is an attractive
      option for managing refractory cancer pain. In suitable patients, IDDS can
      provide reliable long-term analgesia without any permanent nerve or plexus
      destruction. IDDS can also allow patient care on an outpatient basis. In Taiwan,
      however, the experience of using IDDS in terminally ill cancer patients is very
      limited. METHODS: This retrospective study, describes experience of managing
      totally implantable programmable IDDS in 6 refractory cancer pain patients
      including patient selection, intraspinal morphine trial, surgical techniques,
      complications, and drug adjustment. Pain scores and functional status were
      compared before and after IDDS. RESULTS: By delivering liberal dose of
      intrathecal morphine, patients' pain scores decreased from 10 to 3.5. Due to much
      better pain control and improved quality of life, Eastern Cooperative Oncology
      Group performance status also improved in 4/6 patients. During the mean 5 +/- 4.1
      months of follow-up, two patients experienced pocket seroma, and resolved
      spontaneously after short-term abdominal binder compression. Otherwise, no
      serious complication was noted. CONCLUSION: Intrathecal morphine delivery by
      using totally implantable programmable IDDS is an effective method to relieve
      refractory cancer pain.

PMID- 22656396
TI  - A pediatric clinic-based approach to early literacy promotion--experience in a
      well-baby clinic in Taiwan.
AB  - BACKGROUND/PURPOSE: Reach Out and Read (ROR) is an evidence-based intervention
      situated in pediatric offices and can help pediatricians to promote parents'
      reading to their children. The objective of this study was to determine if the
      program could also achieve good results in different culture, such as in Taiwan.
      METHODS: The intervention group (n=205) was enrolled from a well-baby clinic
      participated in a program modified from ROR (receiving anticipatory guidance and
      an appropriate children's book at a well-baby clinic) at a mean age of 9 months.
      The control group (n=210) was recruited from a general pediatric outpatient
      service at the compatible age. Both groups were queried about the reading habits
      of primary caregivers and the frequency of book sharing with their child. When
      children were at aged 12 to 18 month, follow-up questionnaires were collected.
      RESULTS: At follow-up, ANCOVA analysis indicated that the intervention group
      exhibited significantly greater increase in child-centered literacy scores
      (frequency of shared reading, reading as one of their three favorite interaction
      activities and child interested in shared reading). Caregivers were willing to
      accept their pediatrician's advice to read to their infants. CONCLUSION: In this
      study, the simple intervention, implemented at a well-baby clinic in Taiwan,
      changed Taiwanese parents' attitudes toward the importance of reading with their
      infants and toddlers. As primary health care providers, pediatricians are in a
      unique position to affect and encourage parental behaviors that foster early
      literacy development in children.

PMID- 22656397
TI  - Medium-term course and outcome of schizophrenia depicted by the sixth-month
      subtype after an acute episode.
AB  - BACKGROUND/PURPOSE: The intermediate course of schizophrenia is a complex
      intertwined with the heterogeneity of the illness. This article attempts to
      simplify this complexity using a hypothetical tripartite based on the profile of
      symptoms at 6 months after acute treatment. METHODS: This is a prospective 5-year
      follow-up study including 163 schizophrenic inpatients in northern Taiwan
      comparing patients' demographic data at index admission, scores on the Positive
      and Negative Syndrome Scale (PANSS) for schizophrenia and social function scale
      measured at admission, 6-month follow-up, and annually, and scores on a
      neuropsychologic test battery measured approximately 5 years after recruitment.
      RESULTS: Patients were grouped into three subtypes based on their sixth-month
      symptomatology by Generalized Association Plots, designated as remitted (RM),
      persistent delusion/hallucination (PDH), and markedly blunting (MB) groups. These
      three subtypes presented with similar positive symptom profiles at recruitment,
      yet during follow-up, the PDH group tended to maintain the highest risk of having
      worse clinical symptomatology, social functioning, and neuropsychologic
      functioning, and the RM was the best outcome group. CONCLUSION: This three
      subtype model provides a practical reference to predict medium-term outcomes by
      the subject's response to acute treatment and serves as a model to sort out part
      of the heterogeneous nature of schizophrenia that still should be examined by
      further psychopharmacological, neurobiological, and genetic studies.

PMID- 22656398
TI  - Interleukin-27 and interleukin-12 augment activation of distinct cord blood
      natural killer cells responses via STAT3 pathways.
AB  - BACKGROUND/PURPOSE: Umbilical cord blood is rich in primitive natural killer (NK)
      cells, which are activated by interleukin (IL)-12. It was previously reported
      that a novel IL-12 family cytokine, IL-27 comprised of EBI3 and p28, was elevated
      in maternal serum during normal pregnancy. Thus, we compared the immune
      regulatory functions of IL-27 and IL-12 on mononuclear cells derived from cord
      blood and adult peripheral blood. METHODS: After stimulation with IL-27, IL-12,
      and IL-27 combined with IL-12, the cytotoxicity against BJAB lymphoma cells by
      blood mononuclear cells was performed. Then immunofluorescence staining, reverse
      transcriptase-polymerase chain reaction and Western blotting were used to detect
      the effects of IL-27 and IL-12 in isolated NK cells. RESULTS: IL-27, IL-12, and
      IL-27 combined with IL-12 enhanced the cytotoxicity of adult peripheral blood
      cells and cord blood cells, but the proliferation of distinct subpopulations of
      cells was not evident. Similar results were also obtained with purified cord
      blood NK cells. Interestingly, distinct from IL-12, IL-27 could induce
      aggregation and morphological changes of umbilical cord blood cells. Finally, IL
      27 combined with IL-12 could stimulate increased IL-27 receptor (gp130 and WSX-1)
      transcripts in purified cord blood NK cells. However, the activation of signal
      transducer and activator of transcription 3 (STAT3) in NK cells was only detected
      in the presence of IL-27, but not IL-12 alone. CONCLUSION: From previous results,
      we summarize our current understanding of the augmentation of distinct regulation
      of NK cells by IL-27 and IL-12.

PMID- 22656399
TI  - The influence of corneal wound size on surgically induced corneal astigmatism
      after phacoemulsification.
AB  - BACKGROUND/PURPOSE: To determine whether there is a difference in surgically
      induced astigmatism (SIA) after phacoemulsification for unsutured temporal clear
      corneal incisions of 2.5 mm and 3.5 mm wound sizes. METHODS: This study comprised
      36 eyes of 18 patients who received cataract surgery from a single surgeon.
      Patients were randomly assigned to receive a one-piece intraocular lens (IOL;
      Acrysof SA60AT), through a 2.5 mm incision in one eye, and a three-piece IOL
      (Tecnis Z9000), through a 3.5 mm incision in the contralateral eye. Corneal
      topography was performed preoperatively and also postoperatively at 3, 6, and 12
      weeks. SIA was calculated by means of vector analysis using the Alpins' method.
      RESULTS: The mean SIAs of the groups with 2.5 mm and 3.5 mm incisions were 0.57
      diopter (D) and 0.86 D respectively (p = 0.04) at 3 weeks postoperatively, 0.60 D
      and 0.83 D respectively (p > 0.05) at 6 weeks postoperatively, and 0.58 D and
      0.58 D respectively (p > 0.05) at 12 weeks postoperatively. At 12 weeks
      postoperatively, SIAs of <1.0 D were found in all eyes in the 2.5 mm group and
      93% of eyes in the 3.5 mm group. Forty-four percent of eyes in both groups
      demonstrated SIAs > 0.5 D at 12 weeks postoperatively. The largest SIA was 1.36 D
      in the 3.5 mm group. CONCLUSION: Mean SIA in the 3.5 mm group was larger than
      that in the 2.5 mm group in the early postoperative period, but there was no
      significant difference for the entire observational period.

PMID- 22656400
TI  - Dextromethorphan in the treatment of early myoclonic encephalopathy evolving into
      migrating partial seizures in infancy.
AB  - Epileptic encephalopathy with suppression-burst in electroencephalography (EEG)
      can evolve into a few types of epileptic syndromes. We present here an unusual
      case of early myoclonic encephalopathy that evolved into migrating partial
      seizures in infancy. A female neonate initially had erratic myoclonus movements,
      hiccups, and a suppression-burst pattern in EEG that was compatible with early
      myoclonic encephalopathy. The seizures were controlled with dextromethorphan (20
      mg/kg), and a suppression-burst pattern in EEG was reverted to relatively normal
      background activity. However, at 72 days of age, alternating focal tonic
      seizures, compatible with migrating partial seizures in infancy, were
      demonstrated by the 24-hour EEG recording. The seizures responded poorly to
      dextromethorphan. To our knowledge, this is the first reported case of early
      myoclonic encephalopathy evolving into migrating partial seizure in infancy.
      Whether it represents another age-dependent epilepsy evolution needs more
      clinical observation.

PMID- 22656401
TI  - A case of left homonymous upper quadrantanopia after inferior petrosal sinus
      sampling to investigate acromegaly with empty sella.

PMID- 22656402
TI  - Analysis of a hyperbolic geometric model for visual texture perception.
AB  - We study the neural field equations introduced by Chossat and Faugeras to model
      the representation and the processing of image edges and textures in the
      hypercolumns of the cortical area V1. The key entity, the structure tensor,
      intrinsically lives in a non-Euclidean, in effect hyperbolic, space. Its spatio
      temporal behaviour is governed by nonlinear integro-differential equations
      defined on the Poincare disc model of the two-dimensional hyperbolic space. Using
      methods from the theory of functional analysis we show the existence and
      uniqueness of a solution of these equations. In the case of stationary, that is,
      time independent, solutions we perform a stability analysis which yields
      important results on their behavior. We also present an original study, based on
      non-Euclidean, hyperbolic, analysis, of a spatially localised bump solution in a
      limiting case. We illustrate our theoretical results with numerical
      simulations.Mathematics Subject Classification:  30F45, 33C05, 34A12, 34D20,
      34D23, 34G20, 37M05, 43A85, 44A35, 45G10, 51M10, 92B20, 92C20.

PMID- 22656404
TI  - A survey on electronic communication in pediatric clinics.
AB  - OBJECTIVE: Short message service (SMS) or text messaging is growing in use in
      personal, business, and more recently healthcare matters. If and how a tool used
      in adult healthcare may be transitioned to pediatric patients must be carefully
      studied to minimize potential harms. The current surveys were performed to
      examine approval for the use of SMS among both parents of pediatric patients as
      well as pediatric healthcare practitioners. SUBJECTS AND METHODS: A prospective,
      paper-based survey was distributed to parents of patients attending pediatric
      clinics in our large, urban medical center. An online survey was used to poll
      healthcare providers at all levels who provide care in those same clinics.
      RESULTS: Overall approval was positive for the use of SMS, with appointment
      reminders being felt to be the most likely use for the technology by healthcare
      practitioners. Parental approval was highest when they were able to see the
      answers their children provided, but parents also approved of the use of SMS when
      they could not. CONCLUSION: Among parents and healthcare providers at our large
      urban pediatric clinics, approval for SMS use was high for a large range of
      patient ages and clinical uses.

PMID- 22656403
TI  - Patient and phaRmacist telephonic encounters (PARTE) in an underserved rural
      patient population with asthma: results of a pilot study.
AB  - OBJECTIVE: To assess the feasibility, acceptability, and preliminary impact of a
      telepharmacy intervention in an underserved, rural asthma patient population.
      SUBJECTS AND METHODS: Patients with asthma were randomized to receive either
      standard care or telephone consultations from pharmacists regarding asthma self
      management over a 3-month period. Qualitative interviews were conducted to
      identify participants' attitudes/opinions regarding the intervention. Baseline
      and follow-up surveys assessed asthma control, patient activation, and medication
      utilization. RESULTS: Ninety-eight adults were recruited (78% accrual); 83
      completed the study (15% dropout). Participants reported positive opinions and
      believed the intervention improved their asthma self-management. The intervention
      group had significantly higher patient activation compared with the control
      (p<0.05). There were no significant between-group differences regarding asthma
      control. However, within-group analyses of the intervention group showed an
      improvement in asthma control (p<0.01) and medication adherence (p<0.01). No
      within-group differences were found for the control group. CONCLUSIONS: This
      telepharmacy intervention is feasible and showed indicators of effectiveness,
      suggesting the design is well suited for a robust study to evaluate its impact in
      uncontrolled asthma patients. Pharmacists helping patients manage asthma through
      telecommunications may resolve access barriers and improve care.

PMID- 22656405
TI  - Comparison of effects of dexmedetomidine-ketamine and dexmedetomidine-midazolam
      combinations in transurethral procedures.
AB  - OBJECTIVE: To compare the effects of dexmedetomidine-ketamine and dexmedetomidine
      midazolam combinations on the recovery time, hemodynamic and respiratory
      variables, and side effects in patients undergoing transurethral procedures.
      METHODS: Sixty patients scheduled for elective outpatient transurethral procedure
      were randomized into 2 groups. In the group K, a ketamine-dexmedetomidine
      combination was administered, and in the group M, midazolam-dexmedetomidine was
      administered, to provide sedation/analgesia. Pain and sedation levels were
      assessed using visual analog score (VAS) and Ramsey Sedation Scale, respectively.
      The recovery time was assessed with the scale of Aldrete. Time was measured and
      recorded to the moment at which patient responses brought the Aldrete score to 10
      points. Time to eye opening and length of stay in the recovery room were
      recorded. RESULTS: Group M showed significantly lower mean arterial pressure
      (MAP) values at 5 and 10 minutes during the procedure when compared with group K
      (P = .02 and P = .01, respectively). Visual analogue scale scores were greater in
      group M than in group K at 5 and 10 minutes for the transurethral procedure (P =
      .039 and P = .028, respectively). Sedation scores were similar between groups
      during the procedure. Time to eye opening and length of recovery room stay were
      shorter (P < .001 and P < .001, respectively), and Aldrete scores were greater in
      group K than group M. CONCLUSION: Both combinations provided satisfactory
      sedation levels, but the dexmedetomidine-ketamine combination provided better
      analgesia and hemodynamic stability, with less nausea and vomiting and shorter
      recovery time, than the dexmedetomidine-midazolam combination.

PMID- 22656406
TI  - Lower urinary tract symptoms and diet quality: findings from the 2000-2001
      National Health and Nutrition Examination Survey.
AB  - OBJECTIVE: To evaluate the association between dietary quality and the prevalence
      of lower urinary tract symptoms (LUTS). METHODS: We used urinary symptom and
      dietary data obtained from the 2000-2001 National Health and Nutrition
      Examination Survey (NHANES) for the study. Dietary quality was assessed using the
      10-component United States Department of Agriculture (USDA) Healthy Eating Index
      (HEI). We used bivariate methods to examine rates of LUTS among men with poor
      versus good diets. Multivariable logistic regression was used to calculate odds
      ratios after applying sample weights and controlling for age, race/ethnicity,
      smoking status, diabetes, alcohol intake, and exercise. RESULTS: Our study cohort
      consisted of 1385 men aged >=40 years, of whom 279 (21.1%) reported LUTS. We
      found higher rates of LUTS among men with poor dietary intake of dairy (22.4% vs
      16.4%, P = .013) and among men with poor intake of protein (24.6% vs 17.9%, P =
      .012) as well as among those with overall poor diet (25.8 vs 17.8%, P = .018)
      with little dietary variety (26.1 vs 17.6%, P = .001). On multivariate analysis,
      an unhealthy diet (odds ratios [OR] = 1.7; 95% confidence interval [CI] = 1.05
      2.90) was associated with more LUTS, whereas alcohol intake was protective from
      LUTS (OR = 0.67; 95% CI = 0.48-0.93). CONCLUSION: In an analysis of NHANES data,
      we found that poor diet quality was independently associated with patient
      reported LUTS.

PMID- 22656407
TI  - Sensitivity of human strains of Oxalobacter formigenes to commonly prescribed
      antibiotics.
AB  - OBJECTIVE: To determine the sensitivity of 4 strains of Oxalobacter formigenes
      (Oxf) found in humans--HC1, Va3, CC13, and OxK--to varying concentrations of
      commonly prescribed antibiotics. Oxf gut colonization has been associated with a
      decreased risk of forming recurrent calcium oxalate kidney stones. METHODS: For
      each strain and each antibiotic concentration, 100 MUL of an overnight culture
      and 100 MUL of the appropriate antibiotic were added to a 7-mL vial of oxalate
      culture medium containing 20 mM oxalate. On the fourth day, vials were visually
      examined for growth, and a calcium oxalate precipitation test was performed to
      determine whether Oxf grew in the presence of the antibiotic. RESULTS: All 4 Oxf
      strains were resistant to amoxicillin, amoxicillin/clavulanate, ceftriaxone,
      cephalexin, and vancomycin, and they were all sensitive to azithromycin,
      ciprofloxacin, clarithromycin, clindamycin, doxycycline, gentamicin,
      levofloxacin, metronidazole, and tetracycline. One strain, CC13, was resistant to
      nitrofurantoin, and the others were sensitive. Differences in minimum inhibitory
      concentration between strains were demonstrated. CONCLUSION: Four human strains
      of Oxf are sensitive to a number of antibiotics commonly used in clinical
      practice; however, minimum inhibitory concentrations differ between strains.

PMID- 22656408
TI  - Myoinositol: does it improve sperm mitochondrial function and sperm motility?
AB  - OBJECTIVE: To evaluate whether an improvement in mitochondrial membrane potential
      was associated with sperm motility amelioration and greater sperm recovery after
      the swim-up procedure. A second purpose was to evaluate the effects of
      myoinositol (MYO) on sperm apoptosis, quality of chromatin compaction, and DNA
      integrity. METHODS: Spermatozoa from 20 normozoospermic men and 20 patients with
      oligo-astheno-teratozoospermia were incubated in vitro with 2 mg/mL of MYO or
      phosphate-buffered saline as a control for 2 hours. After this incubation period,
      sperm motility was evaluated. Flow cytometry was used to analyze the
      mitochondrial membrane potential, phosphatidylserine externalization, chromatin
      compactness, and DNA fragmentation. We also evaluated the total number of motile
      spermatozoa recovered after swim-up after incubation with MYO or phosphate
      buffered saline. RESULTS: MYO significantly increased the percentage of
      spermatozoa with progressive motility in both normozoospermic men and patients
      with oligo-astheno-teratozoospermia. Motility improvement in the latter group was
      associated with a significant increase in the percentage of spermatozoa with high
      mitochondrial membrane potential. MYO had no effects on mitochondrial function in
      spermatozoa from normozoospermic men. Sperm phosphatidylserine externalization,
      chromatin compactness, and DNA fragmentation were unaffected by MYO in both
      groups. After incubation with MYO, the total number of spermatozoa recovered
      after swim-up had improved significantly in both groups. CONCLUSION: These data
      show that MYO increases sperm motility and the number of spermatozoa retrieved
      after swim-up in both normozoospermic men and patients with abnormal sperm
      parameters. In patients with oligo-astheno-teratozoospermia, the improvement in
      these parameters was associated with improved sperm mitochondrial function. These
      findings support the use of MYO in both in vivo- and in vitro-assisted
      reproductive techniques.

PMID- 22656409
TI  - Can conventional magnetic resonance imaging, prostate needle biopsy, or their
      combination predict the laterality of clinically localized prostate cancer?
AB  - OBJECTIVE: To evaluate conventional magnetic resonance imaging (MRI), prostate
      needle biopsy (PBx), and the combination of both tests in predicting the
      laterality of final specimen pathology after radical prostatectomy. METHODS: A
      total of 574 radical prostatectomy cases that had PBx with at least 12 cores and
      preoperative prostate MRI with pelvic coil were included. We analyzed the
      clinicopathologic data with laterality based on PBx and MRI. Unilateral disease
      in combination was defined as unilateral cancer in PBx and at the same time MRI
      findings of undetectable or ipsilateral disease. Cohen's kappa (kappa) was used
      to measure agreement between the laterality data. RESULTS: There were a total of
      316 (55.1%) unilateral cancers detected by PBx, whereas there were 139 (24.2%)
      cases in the final specimen pathology. MRI resulted in 119 (20.7%) undetectable
      and 205 (35.7%) unilateral cancers. Cancer laterality based on final specimen
      pathology had only fair agreements with PBx (kappa = 0.286), MRI (kappa = 0.200),
      and their combination (k = .291). The positive predictive values to predict
      pathologic concurrent unilaterality were only 30.4% (96/316), 25.9% (53/205), and
      34.8% (72/207), respectively. These trends were similar in low-risk cases.
      CONCLUSION: Preoperative PBx, MRI, and the combination of both methods had only a
      fair correlation with the laterality of prostate cancer (PC), even in low-risk
      cases. Approximately two thirds of cases diagnosed as unilateral disease by
      contemporary PBx, MRI, or their combination were not concurrent unilateral
      disease in final pathology. This should be recognized when planning nerve-sparing
      surgery and potentially for candidate selection for focal therapy to treat PC.

PMID- 22656410
TI  - Editorial comment.

PMID- 22656412
TI  - Effect of diabetes mellitus on high-grade prostate cancer detection among
      Japanese obese patients with prostate-specific antigen less than 10 ng/mL.
AB  - OBJECTIVE: To investigate the association of diabetes mellitus (DM) with prostate
      cancer (PCa) risk and grade among Japanese patients undergoing extended biopsy
      and to investigate how obesity modifies these relationships. METHODS: We
      retrospectively evaluated the data from 2038 patients with a prostate-specific
      antigen (PSA) level <10 ng/mL undergoing initial extended biopsy at our
      institutions. The DM history was determined by self-report and medication use.
      Multivariate analyses of DM for PCa risk and grade were done using logistic
      regression. Moreover, we examined whether these associations were modified by the
      body mass index using subgroup analyses (nonobese <25 kg/m(2) or obese >=25
      kg/m(2)) and interaction tests. Cancer grade was classified according to the
      Gleason score (GS): low-grade (GS <=6), intermediate-grade (GS 7), and high-grade
      (GS 8-10). RESULTS: Of 2038 patients, obesity and DM was observed in 606 (30%)
      and 213 (11%), respectively. Also, 836 patients (41%) had positive biopsy
      findings. On multivariate analysis, we found no significant association of DM
      with the risk of overall PCa (P = .106) or the risk of low-grade (P = .735),
      intermediate-grade (P = .119), or high-grade (P = .110) disease. When stratified
      by obesity, the relative risk (RR) of PCa detection for diabetic men apparently
      increased with higher cancer grade (low grade, RR = 1.19, P = .71; intermediate
      grade, RR = 2.01, P = .099; high-grade, RR = 4.03, P = .025). However, in the
      nonobese men, no association was noted between DM and PCa risk, irrespective of
      grade. Obesity modified the effect of DM on high-grade disease risk with a trend
      (P for interaction = .087). CONCLUSION: DM was associated with more aggressive
      PCa detection among Japanese obese patients with gray-zone PSA levels undergoing
      extended biopsy.

PMID- 22656413
TI  - Editorial comment.

PMID- 22656415
TI  - Association between metabolic syndrome and male overactive bladder in a Japanese
      population based on three different sets of criteria for metabolic syndrome and
      the Overactive Bladder Symptom Score.
AB  - OBJECTIVE: To investigate whether metabolic syndrome is a risk factor for
      overactive bladder (OAB) defined by the Overactive Bladder Symptom Score (OABSS).
      METHODS: A digital rectal examination of the prostate and an OABSS questionnaire
      were conducted in 1031 men who visited our hospital for metabolic screening from
      April 2009 to March 2010. The OABSS includes scores for daytime frequency,
      nighttime frequency, urgency, and urgency incontinence. Relationships of OAB
      (defined as OABSS >=3 with an urgency score >=2) with metabolic syndrome
      diagnosed by Japan Society for the Study of Obesity (JASSO), National Cholesterol
      Education Program-Adult Treatment Panel III (NCEP-ATP III), and International
      Diabetes Federation (IDF) criteria were examined. The severity of OAB symptoms
      was compared among younger, middle-aged, and elderly men (<50, 50-64, and >=65
      years old, respectively) with and without metabolic syndrome. RESULTS: Diagnoses
      of metabolic syndrome were made in 16.4%, 16.9%, and 12.0% of the men using
      JASSO, NCEP-ATP III, and IDF criteria, respectively. Regardless of the presence
      of metabolic syndrome, aging was significantly associated with increased rates of
      moderate or severe OABSS findings and OAB defined by the OABSS. In middle-aged
      men, metabolic syndrome had a significant negative association with OAB rate. In
      elderly men, metabolic syndrome had a significant negative association with the
      total OABSS. CONCLUSION: A relationship between age and OAB was observed, but
      metabolic syndrome did not show a clear association with OAB. Our results suggest
      that OAB is associated with aging regardless of the presence of metabolic
      syndrome.

PMID- 22656416
TI  - Penoscrotal reconstruction with gracilis muscle flap and internal pudendal artery
      perforator flap transposition.
AB  - OBJECTIVE: Extensive defects of the perineal area, with exposure of the testes,
      are difficult to reconstruct. For the reconstruction of these defects, we applied
      gracilis muscle flap combined with pudendal artery perforator fasciocutaneous
      flap, which provided us a reliable cutaneous flap and allowed us to cover exposed
      testes with sufficient muscular volume. METHODS: We retrospectively analyzed 7
      patients from 2004-2011 whose penoscrotal defects had been reconstructed using
      gracilis muscle flap and an internal pudendal artery perforator flap. Six had
      Fournier's gangrene and 1 had extramammary Paget's disease. We examined
      characteristics of the patients, preoperative management, operative procedure,
      and their clinical courses. RESULTS: All flaps survived during the entire follow
      up periods. The mean width of the defects was 10.14 cm and the mean length was
      9.29 cm. The width of the fasciocutaneous flap was approximately 6-10 cm, whereas
      the length ranged from 10-15 cm. The reconstructed areas were in good functional
      and esthetic conditions. CONCLUSION: The combination of the gracilis muscle flap
      and the internal pudendal artery perforator fasciocutaneous flap provides pliable
      and reliable soft tissue coverage for extensive penoscrotal defects with adequate
      bulkiness and minimal donor site morbidity.

PMID- 22656417
TI  - Editorial comment.

PMID- 22656419
TI  - Re: Greene et al.: Comparison of a reduced radiation fluoroscopy protocol to
      conventional fluoroscopy during uncomplicated ureteroscopy (Urology 2011;78:286
      290).

PMID- 22656421
TI  - Re: Ito et al. Prognostic impact of C-reactive protein for determining overall
      survival of patients with castration-resistant prostate cancer treated with
      docetaxel (Urology 2011;78:1131-1135).

PMID- 22656423
TI  - Re: Bjurlin et al.: Bicycle-related genitourinary injuries (Urology.
      2011;78(5):1187-1190).

PMID- 22656425
TI  - Robotic-assisted laparoscopic prostatectomy in umbilical hernia patients:
      University of California, Irvine, technique for port placement and repair.
AB  - OBJECTIVE: To discuss a technique currently used at our institution for the
      management of umbilical hernias during robot-assisted laparoscopic prostatectomy.
      As more patients undergo robot-assisted radical prostatectomy, there will be an
      increase in patients who qualify for robotic surgery with comorbidities. MATERIAL
      AND METHODS: This technique has been utilized in clinically localized prostate
      cancer patients with umbilical hernias using the da Vinci Surgical System and
      standard laparoscopic instrumentation. Port placements and closures were
      performed by a resident assistant and a nurse at the operating table. The
      prostatectomy was performed by a single experienced surgeon at the console.
      RESULTS: Currently, no data are available regarding patients with umbilical
      hernias undergoing robotic prostatectomy. We reviewed our technique of port
      placement for patients with a pre-existing umbilical hernia undergoing robot
      assisted laparoscopic prostatectomy. CONCLUSION: This technique allows for a
      reduction of the umbilical hernia, the use of the fascial defect as a robotic
      port, and the removal of the prostate by way of transverse incision and
      transverse repair. In our experience, this technique is feasible and reproducible
      for any small or large umbilical hernia.

PMID- 22656426
TI  - IVC tumor thrombus: an advanced case of rare extraosseous Ewing sarcoma of the
      adrenal gland.
AB  - Extraosseous Ewing sarcoma (ES) of the adrenal gland is a rare, aggressive tumor
      of young adults, with <10 cases reported. We present the radiological findings of
      an unusual case of adrenal and renal vein tumor thrombosis extending into the
      inferior vena cava, secondary to ES of the adrenal gland in a 26-year-old female.

PMID- 22656427
TI  - Basal cell carcinoma of the prostate: a case report.
AB  - A 69-year-old man presented with gross hematuria and irritative urinary symptoms.
      He underwent transurethral resection of his prostate. The prostate chips revealed
      70% poorly differentiated carcinoma with neuroendocrine features, initially read
      as small cell carcinoma, later as basal cell carcinoma. PSA at this time was 0.3.
      He received 4 cycles of etoposide and cisplatin. After which, rebiopsy of the
      prostate showed tumor consistent with poorly differentiated basal cell carcinoma.
      Given progression on chemotherapy, decision was made to proceed with radical
      prostatectomy. Metastatic workup was negative. Gross extraprostatic invasion was
      noted but lymph nodes were free of metastatic disease.

PMID- 22656428
TI  - Clear cell adenocarcinoma arising from abdominal wall endometriosis mimicking
      urachal tumor.
AB  - A 41-year-old woman presented with severe lower abdominal pain. She had a history
      of 2 cesarean deliveries. Magnetic resonance imaging (MRI) revealed a 4.3 * 4.6 *
      4.8-cm mass on the urinary bladder dome. Preoperative diagnosis was invasive
      urachal tumor. Wide resection of the tumor was performed. The histopathological
      diagnosis was clear cell adenocarcinoma with endometriosis. MRI revealed normal
      sized ovaries and uterus. The definite diagnosis of clear cell carcinoma arising
      from abdominal wall endometriosis was made. Adjuvant chemotherapy with paclitaxel
      and carboplatin (total 6 courses) was planned. The patient has thus far received
      4 courses of this treatment.

PMID- 22656430
TI  - Giving and receiving feedback.

PMID- 22656431
TI  - Should you have a speakers' table?
AB  - Should speakers have special, reserved seating at conferences? This column
      describes the pros and cons of having designated seating for presenters.

PMID- 22656432
TI  - Nurses' critical role in identifying sepsis and implementing early goal-directed
      therapy.
AB  - Nurses play a critical role in detecting early sepsis-related manifestations and
      improving adherence to implementation of early goal-directed therapy. Educating
      staff about sepsis management through translation of best practices is critical
      to improving sepsis-related outcomes.

PMID- 22656433
TI  - Keeping the patient focus: using tablet technology to enhance education and
      practice.
AB  - Nurses are busy. Technology places a vast amount of information at their
      fingertips.

PMID- 22656435
TI  - Frequent attendance in family practice and common mental disorders in an open
      access health care system.
AB  - Frequent attenders in family practice are known to have higher rates of mental
      disorder. However little is known about specific psychiatric disorders and
      whether this behavior extends to specialist services, in an open access fee-for
      service health care system. METHODS: 1060 patients from 46 family practices
      completed the Patient Health Questionnaire and the Client Service Receipt
      Inventory. During the consultation, family practitioners blind to the
      questionnaire responses rated the severity of mental health and physical
      disorders. The 10% of patients with the highest number of 6-month consultations
      in six age and sex stratified groups were defined as frequent attenders. RESULTS:
      After adjustments for sociodemographic variables, physical health and other
      psychiatric diagnoses, patients with a somatoform disorder were more likely to be
      frequent attenders, with an odds ratio of 2.3 (95% CI: 1.3-3.8, p=.002).
      CONCLUSION: When adjusting for confounders, among the four psychiatric diagnoses
      investigated only somatoform disorders remain significantly associated with
      frequent attendance. Physical health and chronic disease were no longer
      associated with frequent attendance which does not support the hypothesis that in
      an open access fee-for-service system, patients will consult for a wider range of
      health problems. Greater investigation into unexplained somatic symptoms could
      help reduce the frequency of attendance in both primary and secondary care, as
      this behaviour appears to be a general health-seeking drive than extends beyond
      family practice.

PMID- 22656429
TI  - Unique structure and regulation of the nematode detoxification gene regulator,
      SKN-1: implications to understanding and controlling drug resistance.
AB  - Nematodes parasitize an alarming number of people and agricultural animals
      globally and cause debilitating morbidity and mortality. Anthelmintics have been
      the primary tools used to control parasitic nematodes for the past several
      decades, but drug resistance is becoming a major obstacle. Xenobiotic
      detoxification pathways defend against drugs and other foreign chemicals in
      diverse organisms, and evidence is accumulating that they play a role in
      mediating resistance to anthelmintics in nematodes. Related antioxidation
      pathways may also provide filarial parasites with protection against host free
      radical-mediated immune responses. Upstream regulatory pathways have received
      almost no attention in nematode parasites, despite their potential to coregulate
      multiple detoxification and antioxidation genes. The nuclear eurythroid 2-related
      factor 2 (NRF2) transcription factor mediates inducible detoxification and
      antioxidation defenses in mammals, and recent studies have demonstrated that it
      promotes multidrug resistance in some human tumors. Recent studies in the free
      living model nematode, Caenorhabditis elegans, have defined the homologous
      transcription factor, SKN-1, as a master regulator of detoxification and
      antioxidation genes. Despite similar functions, SKN-1 and NRF2 have important
      differences in structure and regulatory pathways. Protein alignment and
      phylogenetic analyses indicate that these differences are shared among many
      nematodes, making SKN-1 a candidate for specifically targeting nematode
      detoxification and antioxidation.

PMID- 22656436
TI  - Is co-morbid depression adequately treated in patients repeatedly referred to
      specialist medical services with symptoms of a medical condition?
AB  - OBJECTIVE: Patients with a medical condition and co-morbid depression have more
      symptoms and use more medical services. We aimed to determine the prevalence of
      depression and the adequacy of its treatment in patients who had been repeatedly
      referred from primary to specialist medical care for the assessment of a medical
      condition. METHODS: All patients who had at least three referrals to medical and
      surgical specialists for an assessment of symptoms attributed to a medical
      condition, over a five year period from five primary care practices in Edinburgh,
      UK were identified using a referral database and review of records. Participants
      were sent a questionnaire which included the PHQ-9 depression scale and
      additional questions about depression during the preceding 5years. Details of
      treatment for depression were obtained from primary care records. RESULTS:
      Questionnaires were sent to 230 patients and returned by 162 (70.4%). Forty-one
      (25.3%) had a PHQ-9 score of 10 or more and hence probable current depressive
      disorder. An additional 36 (22.2%) reported depression in the previous 5years.
      Only eight (19.5%) of those reporting current depression and 20 (26%) of the 77
      patients reporting previous depression had received minimally adequate treatment
      for it. CONCLUSION: Whilst we know that patients with medical conditions are
      often depressed and that such co-morbid depression is often undertreated, we have
      found that it is undertreated even in patients repeatedly referred to medical
      specialists. Better assessment and management of depression in such patients
      could both improve patients' quality of life and reduce the cost of care.

PMID- 22656437
TI  - Type D personality and three-month psychosocial outcomes among patients post
      myocardial infarction.
AB  - OBJECTIVE: Type D personality has been proposed as a risk factor for poor
      prognosis in cardiac patients. Recent studies which have adopted a dimensional
      approach to Type D (negative affectivity*social inhibition) found no effect of
      Type D on mortality, after controlling for its constituent elements. To-date, no
      study has determined if Type D is associated with psychosocial outcomes in post
      myocardial infarction (MI) patients when conceptualised as a dimensional
      variable. METHODS: Participants were 192 MI patients (138 males, 54 females, mean
      age 66.0years) who provided demographic and clinical information, and completed
      measures of Type D one-week post-MI. Three months later, 131 of these MI patients
      completed measures of disability and quality of life. RESULTS: Using regression
      analyses, adjusted for demographic and clinical data, Type D emerged as a
      significant predictor of disability and quality of life in MI patients, when
      analysed using the traditional categorical approach. However, Type D did not
      predict disability and quality of life when it was analysed using the interaction
      of negative affectivity and social inhibition. Negative affect emerged as a
      significant predictor of both disability (beta=.433, t(130)=3.53, p<.01), and
      quality of life (beta=-.624, t(130)=-5.68, p<.001). CONCLUSIONS: The results
      suggest that Type D is not associated with short-term psychosocial outcome in MI
      patients, after controlling for its constituent elements. However, negative
      affect was significantly associated with both disability and quality of life.
      Future research should conceptualise Type D as the interaction between negative
      affectivity and social inhibition, rather than as a typology.

PMID- 22656438
TI  - Profiling illness perceptions to identify patients at-risk for decline in health
      status after heart valve replacement.
AB  - OBJECTIVE: Identification of risk factors for decline in health status by
      profiling illness perceptions before and one year after heart valve replacement
      surgery. METHODS: Prospective data from N=225 consecutively admitted first time
      valve replacement patients was assessed before and one year after surgery.
      Patients were asked about their illness perceptions (Illness Perception
      Questionnaire-Revised) and mood state (Hospital Anxiety and Depression Scale).
      Health status was defined by quality of life (Short-Form 36) and New York Heart
      Association (NYHA) class. Cluster analyses were conducted to identify illness
      perception profiles over time. Predictors of health status after surgery were
      analyzed with multivariate methods. RESULTS: Patients were grouped according to
      the stability and nature (positive, negative) of their illness perception profile
      over one year. One year after surgery patients holding a negative illness
      perception profile showed a lower physical quality of life and were diagnosed in
      a higher New York Heart Association class than patients changing to positive and
      patients with stable positive illness perceptions (P<.001). Over and above
      biological determinants, post-surgery physical quality of life and NYHA class
      were both predicted by pre-surgery illness perception profiles (P<.05).
      CONCLUSION: Patients going for heart valve replacement surgery can be easily
      categorized into illness perception profiles that predict health status one year
      after surgery. These patients could benefit from early screening as negative
      illness perceptions are modifiable risk factors.

PMID- 22656439
TI  - Post-traumatic stress disorder (PTSD) in cardiology and oncology--which
      diagnostic tools should be used?
AB  - OBJECTIVES: PTSD prevalence rates in cardiac and cancer patients greatly vary
      probably due to diverging samples, designs and assessments. Aim of this study was
      therefore to compare prevalence rates of PTSD as well as instruments assessing
      PTSD in different cardiac and cancer patient groups. METHODS: A total of 274
      cardiac and cancer patients were examined with the Post-Traumatic Stress Scale 10
      (PTSS-10) and the Impact of Event Scale - revised (IES-R). Presence of PTSD was
      validated by Structured Clinical Interview for DSM-IV (SCID). RESULTS: Diagnostic
      criteria for the existence of PTSD were met by 29.2% of all patients via PTSS-10,
      by 7.6% in IES-R and by 4.8% in SCID, indicating substantial discrepancy among
      assessments. This is further underlined by the moderate correlation between self
      reports and poor agreement with the standardised interview. CONCLUSION: A
      structured interview is the "gold standard" for diagnosing PTSD in cardiac and
      cancer patients. Questionnaires can be used as screening instruments when they
      reliably assess trauma-related diagnostic criteria. Further studies are necessary
      to clarify the specifics of trauma criteria in medical setting.

PMID- 22656440
TI  - Sleepiness and sleep quality in patients with HIV infection.
AB  - OBJECTIVES: Patients with HIV infection frequently complain of sleep disturbances
      and daytime sleepiness. Only few data on these problems evaluated by standardized
      measures is available. METHODS: A sample of 180 consecutive patients with HIV
      infection referred to the internal and to the neurological HIV clinics at the
      University of Munster was enrolled in this study. The data were compared to a
      sample of 120 age- and sex-matched control subjects. We used the Epworth
      Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and the Beck's
      Depression Inventory (BDI). In addition, the clinical and immunological data of
      the patients were registered. RESULTS: All scores of the ESS, the PSQI, and the
      BDI were significantly increased in the HIV infected patients as compared to the
      control group. There were no significant correlations between any of the immune
      parameters and the scores. Only a higher BDI score was correlated with both the
      ESS score and the PSQI score. CONCLUSIONS: Patients with HIV infection and not
      using evavirenz show an increased daytime sleepiness and a decreased quality of
      sleep. These findings could not be related to the immunological state of the
      patients. The only specific factor influencing daytime sleepiness in HIV infected
      patients is probably treatment with HAART. The most important factor determining
      sleepiness and sleep quality in HIV infected patients is depression which was
      found to be independent from the immunological state and HAART of the patients.

PMID- 22656441
TI  - Dynamic risk factors in the misuse of opioid analgesics.
AB  - OBJECTIVE: Identify the risk factors for prescription opioid misuse among
      patients taking prescription opioids to deal with chronic pain. METHODS: We
      examined the literature for a variety of dynamic risk factors associated with
      opioid misuse among the chronic pain population in order to present a narrative
      review. Considered were: taking single or multiple opioids, pain intensity,
      mental health disorders, including a history of preadolescent sexual abuse,
      personal and familial history of substance abuse, a history of legal problems,
      being a crime victim, drug-seeking behaviors, drug craving, and age. RESULTS: A
      variety of risk factors have been studied in the literature. Risk factors in
      chronic opioid therapy patients are dynamic in that they can change with disease
      progression, tolerance, changes in pain quality, mental health, comorbidities,
      other drug therapies or drug interactions, and changes in the patient's
      lifestyle. CONCLUSION: Opioid analgesic therapy must be tailored to carefully
      monitor all patients in order to minimize misuse and abuse, since the risk is
      constant and dynamic and therefore every patient is at some degree of risk for
      opioid misuse.

PMID- 22656442
TI  - Pain and the relationship with mood and anxiety disorders and psychological
      symptoms.
AB  - OBJECTIVE: The objective of this study was to investigate the association between
      pain and mood and anxiety disorders, as well as psychological symptoms, in a
      population-based sample of women. METHODS: This study examined the data collected
      from 1067 women aged 20-93years (median 51years) participating in the Geelong
      Osteoporosis Study. Mood and anxiety disorders were diagnosed using a clinical
      interview (SCID-I/NP) and psychological symptomatology was assessed using the
      General Health Questionnaire. Pain was determined using a Visual Analogue Scale
      (0-100mm) and deemed present if score>=40mm. RESULTS: Current mood disorders were
      associated with an increased likelihood of overall (OR=3.2, 95% CI 2.0-5.1),
      headache (OR=2.8, 95% CI 1.6-4.8), back (OR=4.0, 95% CI 2.5-6.5) and shoulder
      pain (OR=2.2, 95% CI 1.2-4.2). In those with current mood disorders, the pain
      interfered with daily activities (OR=3.2, 95% CI 1.9-5.5) and was present most of
      their time awake (OR=2.5, 95% CI 1.5-4.1). This pattern was similarly observed
      for those with past mood disorders. Current anxiety disorders were associated
      with an increased likelihood for overall (OR=2.2, 95% CI 1.4-3.6), headache
      (OR=2.2, 95% CI 1.3-4.0), back (OR=1.8, 95% CI 1.1-3.0) and shoulder pain
      (OR=1.9, 95% CI 1.0-3.5, p=.05). In those with current anxiety disorders, the
      pain interfered with daily activities (OR=2.4, 95% CI 1.4-4.1) and was present
      most of their time awake (OR=1.9, 95% CI 1.2-3.2). There was no association
      between pain and past anxiety. Psychological symptomatology was associated with
      pain at each site (all p<.001). CONCLUSIONS: This study is consistent with
      studies utilising clinical samples in reporting that mood and anxiety disorders,
      as well as psychological symptoms, are associated with higher levels of perceived
      pain.

PMID- 22656444
TI  - Training in consultation-liaison psychiatry in Eastern Europe.

PMID- 22656443
TI  - The teaching of liaison psychiatry.
AB  - OBJECTIVE: To document performance and satisfaction of medical students in a
      short course on liaison psychiatry. METHODS: The emphasis in this optional course
      is placed on the discussion of clinical cases, bed-side clinical teaching, and a
      research-oriented part. The "Innovative Teaching Plan" (ITP) is intended to train
      student-leaders to guide small groups (SG) of students. Trainee performance was
      assessed by the marks in the final examination, and a reliable and valid tool,
      the Medical Teaching Quality Questionnaire (MTQQ) was used to document trainee
      satisfaction. The results of four academic courses are presented in this report.
      RESULTS: External experts consulted assured that the content of the course was
      adequate. It has been completed by more than 200 medical students, and high marks
      have been obtained by most. Above average scores (AA, "high" or "very high") were
      given by substantial proportions of students in most items, related to the
      "relevance" of the subject, the "usefulness of the clinical cases" or the
      "enhancement of student-teacher interaction". Compared to the first academic
      course, students' satisfaction has improved. "Enhancement of a researcher's mind"
      was rated AA by 61.1% of students in the last academic course, and "global
      satisfaction" by 88.8%. CONCLUSIONS: Good performance and high satisfaction of
      medical students was documented in a course on liaison psychiatry. Lessons may be
      drawn to inform about efficient and effective ways of teaching and learning this
      subject.

PMID- 22656445
TI  - A nurse-led mental health service for people with multiple sclerosis.
AB  - BACKGROUND: Mental health problems are under recognised and under treated in
      people with multiple sclerosis (MS). METHOD: A nurse-led project linking MS and
      mental health services was evaluated. Data on all referrals and management from
      2006 to 2008 were collected prospectively. RESULTS: 127 referrals were received.
      82% had depression, 53% had anxiety (45% both). 42% were offered case management;
      52% received Cognitive Behaviour Therapy (CBT), 55% required initiation or
      alteration of psychiatric medications and 19% were referred to secondary care;
      16% had made suicidal plans. Significant improvements in depression at 6months
      occurred, but not anxiety or fatigue. CLINICAL IMPLICATIONS: This service
      provides a model of mental health provision for patients with long term
      neurological conditions, in particular MS.

PMID- 22656447
TI  - An oxygen release system to augment cardiac progenitor cell survival and
      differentiation under hypoxic condition.
AB  - Stem cell therapy has the potential to regenerate heart tissue damaged by
      myocardial infarction (MI), but it experiences extremely low efficacy. One of the
      major causes is the inferior cell survival under hypoxic condition of the
      infarcted hearts. We examined whether an oxygen-releasing system capable of
      sustainedly supplying oxygen to stem cells would augment cell survival and
      cardiac differentiation under hypoxic condition mimicking that of the infarcted
      hearts. The oxygen-releasing system consisted of hydrogen peroxide (H(2)O(2))
      releasing microspheres, catalase and an injectable, thermosensitive hydrogel. The
      microspheres were based on poly(lactide-co-glycolide) (PLGA) and a complex of
      H(2)O(2) and poly(2-vinlypyrridione) (PVP). The oxygen was generated after the
      released H(2)O(2) was decomposed by catalase. The hydrogel was designed to
      improve the retention of microspheres and stem cells in the beating heart tissue
      during myocardial injection. The oxygen-releasing system was capable of
      sustainedly releasing oxygen for at least two weeks. The release kinetics was
      dependent on the ratio of H(2)O(2)/VP. The hydrogel was based on N
      isopropylacrylamide (NIPAAm), acrylic acid (AAc), and a macromer hydroxyethyl
      methacrylate-oligo(hydroxybutyrate) (HEMA-oHB). The hydrogel had a stiffness
      matching that of the heart tissue and was able to stimulate the cardiosphere
      derived cells (CDCs) to differentiate into cardiomyocytes. Under hypoxic
      condition mimicking that of the infarcted hearts (1% O(2)), CDCs encapsulated in
      the hydrogel experienced massive cell death. Introduction of oxygen release in
      the hydrogel significantly augmented cell survival; no cell death was found after
      seven days of culture, and cells even grew after seven days. Under hypoxic
      condition, cardiac differentiation of CDCs was completely silenced in the
      hydrogel, as confirmed at both mRNA and protein levels. However, introduction of
      oxygen release restored the differentiation. These results demonstrate that the
      developed oxygen-releasing system has great potential to improve the efficacy of
      cardiac stem cell therapy.

PMID- 22656446
TI  - Substrate dependent stability of conducting polymer coatings on medical
      electrodes.
AB  - Conducting polymer (CP) coatings on medical electrodes have the potential to
      provide superior performance when compared to conventional metallic electrodes,
      but their stability is strongly dependant on the substrate properties. The aim of
      this study was to examine the effect of laser roughening of underlying platinum
      (Pt) electrode surfaces on the mechanical, electrical and biological performance
      of CP coatings. In addition, the impact of dopant type on electrical performance
      and stability was assessed. The CP poly(ethylene dioxythiophene) (PEDOT) was
      coated on Pt microelectrode arrays, with three conventional dopant ions. The in
      vitro electrical characteristics were assessed by cyclic voltammetry and biphasic
      stimulation. Results showed that laser roughening of the underlying substrate did
      not affect the charge injection limit of the coated material, but significantly
      improved the passive stability and chronic stimulation lifetime without failure
      of the coating. Accelerated material ageing and long-term biphasic stimulus
      studies determined that some PEDOT variants experienced delamination within as
      little as 10 days when the underlying Pt was smooth, but laser roughening to
      produce a surface index of 2.5 improved stability, such that more than 1.3
      billion stimulation cycles could be applied without evidence of failure. PEDOT
      doped with paratoluene sulfonate (PEDOT/pTS) was found to be the most stable CP
      on roughened Pt, and presented a surface topography which encouraged neural cell
      attachment.

PMID- 22656448
TI  - The interactions of amphiphilic antisense oligonucleotides with serum proteins
      and their effects on in vitro silencing activity.
AB  - Antisense oligonucleotides (AONs) are a class of compounds with high therapeutic
      potential. One of the challenges facing this platform is the development of
      effective techniques to achieve cellular delivery. AON conjugates, in which
      traditional AONs are attached to certain biomolecules, can exhibit improved
      intracellular bioavailability in the absence of delivery systems. In this study,
      the lipophilic moieties docosahexaenoic acid, cholesterol, and docosanoic acid
      (DSA) were conjugated to various phosphorothioated DNA and chemically-modified 2'
      fluoro-arabinonucleic acid AONs via an amino-hexanol-linker added to the 5'-end
      of the molecule. The gene silencing potential of these compounds was evaluated in
      vitro in the absence or presence of a transfecting agent (polyion complex
      micelle). Incubation with sub-micromolar concentration of DSA-conjugates could,
      in the absence of serum proteins, downregulate more than 60% of the targeted mRNA
      under carrier-free and carrier-loaded delivery methods. Gene silencing activity
      of carrier-free DSA-conjugates was, however, decreased in a dose-dependent
      fashion by adding albumin in the transfection medium. Supplementing the medium
      with free fatty acid prevented the interaction of the DSA-conjugate with albumin,
      and restored its silencing activity. These findings suggest that strategies
      aiming at preventing the association of hydrophobized AONs to serum proteins at
      the site of action may improve their activity.

PMID- 22656449
TI  - An aligned 3D neuronal-glial co-culture model for peripheral nerve studies.
AB  - In this study we report on the development of a 3D in vitro peripheral nerve
      model using aligned electrospun polycaprolactone fibre scaffolds manufactured
      under tightly controlled and reproducible conditions with uniform diameters of 1
      MUm, 5 MUm and 8 MUm. Fibres were characterized by SEM for diameter, density and
      alignment properties and formed in to scaffolds for 3D in vitro culture. Three
      different approaches were adopted using: i) neuronal or primary Schwann cell
      cultures alone; ii) neuronal and primary Schwann cells in co-culture and iii)
      isolated dorsal root ganglion cultures, containing both neuronal and Schwann
      cells, with immunohistochemical and 3D confocal microscopy analysis. Neurite
      guidance was evident on all fibres diameters with the longest neurites detected
      on 8 MUm fibres when cultured alone. However, co-culture with primary Schwann
      cells was found to enable neurite formation on all scaffolds. Dorsal root
      ganglion explants when grown on scaffolds showed both organised aligned neurite
      guidance and notably the co-localization of Schwann cells with neurites. Neurite
      lengths of up to 2.50 mm were routinely observed using 1 MUm diameter fibres
      after 10 days and all cultures demonstrated a migrating Schwann cell 'front' of
      up to 2.70 mm (1 MUm diameter fibres). Thus, a direct relationship was found
      between fibre diameter, neurite outgrowth and Schwann cell morphology. This work
      therefore supports the use of aligned electrospun PCL microfibres for the
      development of 3D peripheral nerve models in vitro. We envisage such models
      having future value in a number of areas including developmental biology, disease
      studies and the design of devices and scaffolds for peripheral nerve repair.

PMID- 22656451
TI  - Martek instruments, inc.

PMID- 22656450
TI  - TGFbeta and BMP signaling in cardiac cushion formation: lessons from mice and
      chicken.
AB  - Cardiac cushion formation is crucial for both valvular and septal development.
      Disruption in this process can lead to valvular and septal malformations, which
      constitute the largest part of congenital heart defects. One of the signaling
      pathways that is important for cushion formation is the TGFbeta superfamily. The
      involvement of TGFbeta and BMP signaling pathways in cardiac cushion formation
      has been intensively studied using chicken in vitro explant assays and in
      genetically modified mice. In this review, we will summarize and discuss the role
      of TGFbeta and BMP signaling components in cardiac cushion formation.

PMID- 22656452
TI  - Molecules dimensions in science.

PMID- 22656454
TI  - Industry participation in the regulatory process.

PMID- 22656455
TI  - International.

PMID- 22656456
TI  - Washington.

PMID- 22656457
TI  - States.

PMID- 22656459
TI  - Awards.

PMID- 22656458
TI  - Science.

PMID- 22656461
TI  - Industry.

PMID- 22656460
TI  - Technology.

PMID- 22656462
TI  - Arctic haze.

PMID- 22656463
TI  - Introducing new chemicals.

PMID- 22656464
TI  - Report from the spring ACS meeting.

PMID- 22656465
TI  - EPA budget debated.

PMID- 22656466
TI  - Air pollutants and forest decline.

PMID- 22656467
TI  - Air quality research, inc.

PMID- 22656468
TI  - Quality assurance for emissions analysis systems.

PMID- 22656469
TI  - Chemical & engineering news.

PMID- 22656470
TI  - Products.

PMID- 22656472
TI  - Literature.

PMID- 22656473
TI  - Courses.

PMID- 22656474
TI  - CHEMetrics, Inc.

PMID- 22656475
TI  - Electric power research institute.

PMID- 22656476
TI  - International.

PMID- 22656478
TI  - Classified section.

PMID- 22656480
TI  - professional consulting services directory.

PMID- 22656640
TI  - Two metal-organic frameworks constructed from one-dimensional cobalt(II)
      ferrimagnetic chains with alternating antiferromagnetic/ferromagnetic and
      AF/AF/FM interaction: synthesis, structures, and magnetic properties.
AB  - Here, we report two three-dimensional metal-organic frameworks of formula
      [Co(2)(4-ptz)(2)(bpp)(N(3))(2)](n) (1) and
      [Co(3)(OH)(2)(bdt)(2)(bpp)(2)(H(2)O)(2)](n) (2), which were synthesized by
      hydrothermal reaction from the respective tetrazole ligand (5-(4
      pyridyl)tetrazole (4-H-ptz) for 1 and 5,5'-(1,4-phenylene)bis(1-H-tetrazole)
      (H(2)bdt) for 2), long and flexible pyridyl-containing ligand 1,3-bi(4
      pyridyl)propane (bpp), NaN(3), and CoCl(2). Both 1 and 2 consist of well-isolated
      one-dimensional cobalt(II) alternating chains further linked by the bpp and/or
      the tetrazole ligand, while their chain structures are totally different. The
      chains of 1 are formed by Co(2+) ions bridged by single MU-EE-N(3) and triple (MU
      EO-N(3))(MU-tetrazole)(2) alternately, whereas the Co(2+) ions are bridged by
      MU(3)-OH to form Co(3)(OH)(2) chains in compound 2. Magnetic measurements
      demonstrate that compound 1 contains an alternating antiferromagnetic
      (AF)/ferromagnetic (FM) ferrimagnetic chain, while compound 2 exhibits the
      coexistence of spin canting, slow magnetic dynamics, and finite-size effect, with
      alternating AF/AF/FM ferrimagnetic chains.

PMID- 22656641
TI  - Mutagenicity and cytotoxicity in patients submitted to ionizing radiation.
AB  - OBJECTIVES: To evaluate and compare mutagenicity (micronucleus) and cytotoxicity
      (karyorrhexis, pyknosis, and karyolysis) in exfoliated buccal mucosa cells of
      children following cone beam computed tomography (CBCT) or conventional
      radiograph exposure necessary for orthodontic planning. MATERIALS AND METHODS: A
      total of 49 healthy children were submitted to CBCT or a conventional orthodontic
      radiographic protocol; they were divided into two groups based on exam: CBCT (n 
      =  24) and Radiographic Set (n  =  25) groups. The micronucleus test in the
      exfoliated buccal mucosa cells was applied. RESULTS: There was not a
      statistically significant difference (P > .05) found between the number of
      micronucleated buccal mucosa cells (MNC) before and after exposure to radiation
      in either group, showing that neither group experienced a mutagenic effect.
      However, radiation did cause other nuclear alterations closely related to
      cytotoxicity, including karyorrhexis, pyknosis, and karyolysis, in both groups (P
      < .05). The CBCT group presented a greater increase in cell death than was noted
      in the Radiographic Set group (P < .044). CONCLUSION: According to the
      micronucleus test, mutagenicity was not induced by the CBCT or the conventional
      radiographs, but cytotoxicity was verified after these exams, especially after
      CBCT. That might have happened once the CBCT group received a greater radiation
      dose than the Radiographic Set group as a result of the protocols used in
      orthodontic planning for this study.

PMID- 22656642
TI  - Change.

PMID- 22656643
TI  - Functional characterization of amphipathic alpha-helix in the osmoregulatory ABC
      transporter OpuA.
AB  - The ATP-binding-cassette transporter OpuA from Lactococcus lactis is composed of
      two ATPase subunits (OpuAA) and two subunits (OpuABC) with the transmembrane
      domain fused to an extracellular substrate-binding protein. Of the almost 1900
      homologues of OpuA known to date, a subset has an amino-terminal amphipathic
      helix (plus extra transmembrane segment) fused to the core of the transmembrane
      domain of the OpuABC subunit. FRET measurements indicate that the amphipathic
      alpha-helix is located close to the membrane surface, where its hydrophobic face
      interacts with the transport protein rather than the membrane lipids. Next, we
      determined the functional role of this accessory region by engineering the
      amphipathic alpha-helix. We analyzed the consequence of the mutations in intact
      cells by monitoring growth and transport of glycine betaine under normal and
      osmotic stress conditions. More detailed studies were performed in hybrid
      membrane vesicles, proteoliposomes, and bilayer nanodisks. We show that the
      amphipathic alpha-helix of OpuA is necessary for high activity of OpuA but is not
      critical for the biogenesis of the protein or the ionic regulation of transport.

PMID- 22656644
TI  - Interrelationships of food safety and plant pathology: the life cycle of human
      pathogens on plants.
AB  - Bacterial food-borne pathogens use plants as vectors between animal hosts, all
      the while following the life cycle script of plant-associated bacteria. Similar
      to phytobacteria, Salmonella, pathogenic Escherichia coli, and cross-domain
      pathogens have a foothold in agricultural production areas. The commonality of
      environmental contamination translates to contact with plants. Because of the
      chronic absence of kill steps against human pathogens for fresh produce, arrival
      on plants leads to persistence and the risk of human illness. Significant
      research progress is revealing mechanisms used by human pathogens to colonize
      plants and important biological interactions between and among bacteria in
      planta. These findings articulate the difficulty of eliminating or reducing the
      pathogen from plants. The plant itself may be an untapped key to clean produce.
      This review highlights the life of human pathogens outside an animal host,
      focusing on the role of plants, and illustrates areas that are ripe for future
      investigation.

PMID- 22656645
TI  - Gall midges (Hessian flies) as plant pathogens.
AB  - Gall midges constitute an important group of plant-parasitic insects. The Hessian
      fly (HF; Mayetiola destructor), the most investigated gall midge, was the first
      insect hypothesized to have a gene-for-gene interaction with its host plant,
      wheat (Triticum spp.). Recent investigations support that hypothesis. The minute
      larval mandibles appear to act in a manner that is analogous to nematode stylets
      and the haustoria of filamentous plant pathogens. Putative effector proteins are
      encoded by hundreds of genes and expressed in the HF larval salivary gland.
      Cultivar-specific resistance (R) genes mediate a highly localized plant reaction
      that prevents the survival of avirulent HF larvae. Fine-scale mapping of HF
      avirulence (Avr) genes provides further evidence of effector-triggered immunity
      (ETI) against HF in wheat. Taken together, these discoveries suggest that the HF,
      and other gall midges, may be considered biotrophic, or hemibiotrophic, plant
      pathogens, and they demonstrate the potential that the wheat-HF interaction has
      in the study of insect-induced plant gall formation.

PMID- 22656646
TI  - Arthur Kelman: tribute and remembrance.
AB  - With the death of Professor Arthur Kelman at age 90, the plant sciences, and
      particularly the field of plant pathology, lost one of its most influential and
      effective leaders. His long career involved important positions in the
      Departments of Plant Pathology at North Carolina State University (1949-1965) and
      the University of Wisconsin (1965-1989). Recognized not only for his achievements
      in research and his charismatic influence on his numerous students, Arthur was,
      most of all, an extraordinary teacher. He and his students made significant
      contributions in the fields of virulence, ecology, and control of bacterial plant
      pathogens. In addition, he was extremely active in service to professional
      societies, including the American Phytopathological Society, and a major force in
      the development of the International Society for Plant Pathology. In addition, he
      was an influential member of the Council of the National Academy of Sciences,
      and, after retirement from the University of Wisconsin, he served for two years
      as Chief Scientist of the Competitive Grants Program of the US Department of
      Agriculture. He received numerous awards as a teacher and researcher, and felt an
      intense sense of duty to his profession. He was one of the most influential plant
      pathologists of the twentieth century and will be remembered for his great
      intellect and his humanity.

PMID- 22656647
TI  - Are acceptance rates of a national preventive home visit programme for older
      people socially imbalanced?: a cross sectional study in Denmark.
AB  - BACKGROUND: Preventive home visits are offered to community dwelling older people
      in Denmark aimed at maintaining their functional ability for as long as possible,
      but only two thirds of older people accept the offer from the municipalities. The
      purpose of this study is to investigate 1) whether socioeconomic status was
      associated with acceptance of preventive home visits among older people and 2)
      whether municipality invitational procedures for the preventive home visits
      modified the association. METHODS: The study population included 1,023 community
      dwelling 80-year-old individuals from the Danish intervention study on preventive
      home visits. Information on preventive home visit acceptance rates was obtained
      from questionnaires. Socioeconomic status was measured by financial assets
      obtained from national registry data, and invitational procedures were identified
      through the municipalities. Logistic regression analyses were used, adjusted by
      gender. RESULTS: Older persons with high financial assets accepted preventive
      home visits more frequently than persons with low assets (adjusted OR = 1.5
      (CI95%: 1.1-2.0)). However, the association was attenuated when adjusted by the
      invitational procedures. The odds ratio for accepting preventive home visits was
      larger among persons with low financial assets invited by a letter with a
      proposed date than among persons with high financial assets invited by other
      procedures, though these estimates had wide confidence intervals. CONCLUSION:
      High socioeconomic status was associated with a higher acceptance rate of
      preventive home visits, but the association was attenuated by invitational
      procedures. The results indicate that the social inequality in acceptance of
      publicly offered preventive services might decrease if municipalities adopt more
      proactive invitational procedures.

PMID- 22656648
TI  - A prospective multiple case study of the impact of emerging scientific evidence
      on established colorectal cancer screening programs: a study protocol.
AB  - BACKGROUND: Health-policy decision making is a complex and dynamic process, for
      which strong evidentiary support is required. This includes scientifically
      produced research, as well as information that relates to the context in which
      the decision takes place. Unlike scientific evidence, this "contextual evidence"
      is highly variable and often includes information that is not scientifically
      produced, drawn from sources such as political judgement, program management
      experience and knowledge, or public values. As the policy decision-making process
      is variable and difficult to evaluate, it is often unclear how this heterogeneous
      evidence is identified and incorporated into "evidence-based policy" decisions.
      Population-based colorectal cancer screening poses an ideal context in which to
      examine these issues. In Canada, colorectal cancer screening programs have been
      established in several provinces over the past five years, based on the fecal
      occult blood test (FOBT) or the fecal immunochemical test. However, as these
      programs develop, new scientific evidence for screening continues to emerge.
      Recently published randomized controlled trials suggest that the use of flexible
      sigmoidoscopy for population-based screening may pose a greater reduction in
      mortality than the FOBT. This raises the important question of how policy makers
      will address this evidence, given that screening programs are being established
      or are already in place. This study will examine these issues prospectively and
      will focus on how policy makers monitor emerging scientific evidence and how both
      scientific and contextual evidence are identified and applied for decisions about
      health system improvement. METHODS: This study will employ a prospective multiple
      case study design, involving participants from Ontario, Alberta, Manitoba, Nova
      Scotia, and Quebec. In each province, data will be collected via document
      analysis and key informant interviews. Documents will include policy briefs,
      reports, meeting minutes, media releases, and correspondence. Interviews will be
      conducted in person with senior administrative leaders, government officials,
      screening experts, and high-level cancer system stakeholders. DISCUSSION: The
      proposed study comprises the third and final phase of an Emerging Team grant to
      address the challenges of health-policy decision making and colorectal cancer
      screening decisions in Canada. This study will contribute a unique prospective
      look at how policy makers address new, emerging scientific evidence in several
      different policy environments and at different stages of program planning and
      implementation. Findings will provide important insight into the various
      approaches that are or should be used to monitor emerging evidence, the relative
      importance of scientific versus contextual evidence for decision making, and the
      tools and processes that may be important to support challenging health-policy
      decisions.

PMID- 22656649
TI  - 3D structure prediction of TAS2R38 bitter receptors bound to agonists
      phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP).
AB  - The G protein-coupled receptor (GPCR) TAS2R38 is a bitter taste receptor that can
      respond to bitter compounds such as phenylthiocarbamide (PTC) and 6-n
      propylthiouracil (PROP). This receptor was chosen because its four haplotypes
      (based on three residue site polymorphism) hTAS2R38PAV, hTAS2R38AVI, hTAS2R38AAI,
      and hTAS2R38PVV are known to have dramatically different responses to PTC and
      PROP. We aimed to identify the protein-ligand interaction features that determine
      whether the bitter taste signal from this receptor is sent to the cortex. To do
      this we predicted the 3D structures of the TAS2R38 bitter taste receptor using
      our new BiHelix and SuperBiHelix Monte Carlo methods (No experimental
      determinations of the 3D structure have been reported for any taste receptors.).
      We find that residue 262 (2nd position in the polymorphism) is involved in the
      interhelical hydrogen bond network stabilizing the GPCR structure in tasters
      (hTAS2R38PAV, hTAS2R38AAI, and hTAS2R38PVV), while it is not in the nontaster
      (hTAS2R38AVI). This suggests that the hydrogen bond interactions between TM3 and
      TM6 or between TM5 and TM6 may play a role in activating this GPCR. To further
      validate these structures, we used the DarwinDock method to predict the binding
      sites and 3D structures for PTC and PROP bound to hTAS2R38PAV, hTAS2R38AVI,
      hTAS2R38AAI, and hTAS2R38PVV, respectively. Our results show that PTC and PROP
      can form H-bonds with the backbone of residue 262 in the tasters (hTAS2R38PAV,
      hTAS2R38AAI, and hTAS2R38PVV) but not in the nontaster (hTAS2R38AVI). Thus it
      appears that the hydrogen bond interaction between TM3 and TM6 may activate the
      receptor to pass the ligand binding signal to intracellular processes and that
      the H-bond between agonists and residue 262 in tasters is involved in the bitter
      tasting. This is in agreement with experimental observations, providing
      validation of the predicted ligand-protein complexes and also a potential
      activation mechanism for the TAS2R38 receptor.

PMID- 22656650
TI  - Signal processing in the cochlea: the structure equations.
AB  - BACKGROUND: Physical and physiological invariance laws, in particular time
      invariance and local symmetry, are at the outset of an abstract model. Harmonic
      analysis and Lie theory are the mathematical prerequisites for its deduction.
      RESULTS: The main result is a linear system of partial differential equations
      (referred to as the structure equations) that describe the result of signal
      processing in the cochlea. It is formulated for phase and for the logarithm of
      the amplitude. The changes of these quantities are the essential physiological
      observables in the description of signal processing in the auditory pathway.
      CONCLUSIONS: The structure equations display in a quantitative way the subtle
      balance for processing information on the basis of phase versus amplitude. From a
      mathematical point of view, the linear system of equations is classified as an
      inhomogeneous ?--equation. In suitable variables the solutions can be represented
      as the superposition of a particular solution (determined by the system) and a
      holomorphic function (determined by the incoming signal). In this way, a global
      picture of signal processing in the cochlea emerges.

PMID- 22656651
TI  - Ion transport through dimethyl sulfoxide (DMSO) induced transient water pores in
      cell membranes.
AB  - It is well known that dimethyl sulphoxide (DMSO) increases membrane permeability,
      which makes it widely used as a vehicle to facilitate drug delivery across
      biological membranes. However, the mechanism of how DMSO increases membrane
      permeability has not been well understood. Recently, molecular dynamics
      simulations have demonstrated that DMSO can induce water pores in biological
      membranes, but no direct experimental evidence is so far available to prove the
      simulation result. Using FluxOR Tl+ influx assay and intracellular Ca2+ imaging
      technique, we studied the effect of DMSO on Tl+ and Ca2+ permeation across cell
      membranes. Upon application of DMSO on CHO-K1 cell line, Tl+ influx was
      transiently increased in a dose-dependent manner. The increase in Tl+
      permeability induced by DMSO was not changed in the presence of blockers for K+
      channel and Na+-K+ ATPase, suggesting that Tl+ permeates through transient water
      pores induced by DMSO to enter into the cell. In addition, Ca2+ permeability was
      significantly increased upon application of DMSO, indicating that the transient
      water pores induced by DMSO were non-selective pores. Furthermore, similar
      results could be obtained from RAW264.7 macrophage cell line. Therefore, this
      study provided experimental evidence to support the prediction that DMSO can
      induce transient water pores in cell membranes, which in turn facilitates the
      transport of active substances across membranes.

PMID- 22656652
TI  - Risk reanalysis.

PMID- 22656653
TI  - That others may live: lessons learned from the 2011 Denali climbing season.

PMID- 22656654
TI  - The relationship between ski patrols and emergency medical services systems.

PMID- 22656655
TI  - Pulse oximetry and predicting acute mountain sickness: are we asking the right
      questions?

PMID- 22656656
TI  - Oximetry fails to predict acute mountain sickness or summit success during a
      rapid ascent to 5640 meters.
AB  - OBJECTIVE: The purpose of this study was to determine whether arterial oxygen
      saturation (Spo(2)) and heart rate (HR), as measured by a finger pulse oximeter
      on rapid arrival to 4260 m, could be predictive of acute mountain sickness (AMS)
      or summit success on a climb to 5640 m. METHODS: Climbers (35.0 +/- 10.1 years;
      51 men, 5 women) were transported from 2650 m to the Piedra Grande hut at 4260 m
      on Pico de Orizaba within 2 hours. After a median time of 10 hours at the hut,
      they climbed toward the summit (5640 m) and returned, with a median trip time of
      14 hours. The Lake Louise Self-Assessment Scale (LLSS) for AMS, HR, and Spo(2)
      were collected on arrival at the hut and repeated immediately before and after
      the climbers' summit attempts. RESULTS: Average Spo(2) for all participants at
      4260 m before their departure for the summit was 84.4% +/- 3.7%. Thirty-seven of
      the 56 participants reached the summit, and 59% of all climbers met the criteria
      for AMS during the ascent. The Spo(2) was not significantly different between
      those who experienced AMS and those who did not (P = .82); neither was there a
      difference in Spo(2) between summiteers and nonsummiteers (P = .44). Climbers' HR
      just before the summit attempt was not related to AMS but was significantly lower
      for summiteers vs nonsummiteers (P = .04). CONCLUSIONS: The Spo(2) does not
      appear to be predictive of AMS or summit success during rapid ascents.

PMID- 22656657
TI  - Change in oxygen saturation does not predict acute mountain sickness on Jade
      Mountain.
AB  - OBJECTIVE: The purpose of this trial was to establish whether changes in resting
      oxygen saturation (Spo(2)) during ascent of Jade Mountain is useful in predicting
      acute mountain sickness (AMS). AMS-risk factors were also assessed. METHODS: A
      prospective trial was conducted on Jade Mountain, Taiwan from October 18 to
      October 27, 2008. Resting oxygen saturation (Spo(2)) and heart rate (HR) were
      measured in subjects at the trail entrance (2610 m), on arrival at Paiyun Lodge
      (3402 m) on day 1, and at Paiyun Lodge after reaching the summit (3952 m) the
      next day (day 2). AMS was diagnosed with Lake Louise criteria (AMS score >=4). A
      total of 787 subjects were eligible for analysis; 286 (32.2%) met the criteria
      for AMS. RESULTS: Subjects who developed AMS had significantly lower Spo(2) than
      those who did not at the trail entrance (93.1% +/- 2.1% vs 93.5% +/- 2.3%; P =
      .023), on arrival at Paiyun Lodge on day 1 (86.2% +/- 4.7% vs 87.6% +/- 4.3%; P <
      .001), and on the return back to the Paiyun Lodge after a summit attempt on day 2
      (85.5% +/- 3.5% vs 89.6% +/- 3.2%; P < .001), respectively. Trekkers with AMS
      were significantly younger (40.0 vs 43.2 years; P < .001), and had less high
      altitude (>3000 m) travel in the previous 3 months (29.9% vs 37.1%; P = .004).
      CONCLUSIONS: Subjects with AMS had a lower Spo(2) than those without AMS;
      however, the differences between the 2 groups were not clinically significant.
      The results of this study do not support the use of pulse oximetry in predicting
      AMS on Jade Mountain.

PMID- 22656658
TI  - Rare mitochondrial DNA polymorphisms are associated with high altitude pulmonary
      edema (HAPE) susceptibility in Han Chinese.
AB  - BACKGROUND: The role of genetics in determining an individual's susceptibility to
      high altitude pulmonary edema (HAPE) is unclear. However a number of genetic
      polymorphisms have recently been found to be overrepresented in patients with
      HAPE. Changes at the mitochondrial level may play an important role in the human
      body's adaptation to hypoxia. Polymorphisms of mitochondrial DNA (mtDNA) have
      been shown to be responsible for differences in organelle function. Therefore,
      the frequency of mtDNA 3397A/G and 3552T/A polymorphisms were studied to
      determine their potential role in HAPE. OBJECTIVES: To further study the role of
      mtDNA 3397A/G and 3552T/A variations of reduced nicotinamide adenosine
      dinucleotide dehydrogenase 1 in HAPE susceptibility. METHODS: The single
      nucleotide polymorphisms of mtDNA 3397 and 3552 in patients with HAPE (n = 132)
      and their matched control subjects (n = 233) were studied using polymerase chain
      reaction sequencing. RESULTS: The frequency of mtDNA 3397G in the HAPE group
      (2.3%) was significantly higher than that of the control group (0%; P = .021;
      odds ratio, 2.806; 95% confidence interval, 2.443 to 3.223). The frequency of
      mtDNA 3552A in the HAPE group (6.8%) also was significantly higher than in the
      control group (1.7%; P = .012; odds ratio, 4.198; 95% confidence interval, 1.264
      to 13.880). CONCLUSIONS: In this study, we present the first evidence of
      differences in mtDNA polymorphism frequencies between HAPE victims and healthy
      Han Chinese. Genotypes of mtDNA 3397G and 3552A were correlated with HAPE
      susceptibility. This result could contribute to defining the role of the
      mitochondrial genome in the pathogenesis of HAPE.

PMID- 22656659
TI  - The Hawkesbury Canoe Classic: musculoskeletal injury surveillance and risk
      factors associated with marathon paddling.
AB  - OBJECTIVE: The aim of this study was to assess the incidence and risk factors for
      musculoskeletal injury associated with marathon paddling. METHODS: A prospective
      observational cohort study was conducted during the 2006 Hawkesbury Canoe Classic
      (HCC), an annual 111-km paddling race in Sydney, Australia. Before the race, a
      written questionnaire was distributed to competitors to gather information
      regarding their age, gender, type of craft they were competing in, paddling
      experience, HCC experience, training distances, and preceding injuries. The
      paddler's average race speed was also used for analysis. Injuries were recorded
      throughout the race. Logistic regression analysis was used to identify if any of
      the variables were associated with injuries observed during the race. RESULTS:
      Six hundred and twelve paddlers competed in the race, with 298 respondents
      participating in the study. Eighty-eight paddlers with a total of 135 injuries
      presented for medical assessment. More than one third of injuries involved the
      shoulder (35.6%), followed by the thoracic spine (23%), and lumbar spine (17%).
      Men were 3.6 times (CI: 1.39 to 9.32, P = .01) more likely to present with an
      injury compared with the women. A faster average speed (ie, faster finishing
      time) was correlated with a decrease in injury presentation (odds ratio 0.77, CI:
      0.63 to 0.93, P = .01). Modifiable risk factors such as age, type of craft,
      paddling experience, HCC experience, training distances, and preceding injuries
      were not shown to increase the chance of injury presentation. CONCLUSIONS:
      Further data gathered over a series of this race may point to modifiable risk
      factors that may help reduce the incidence of injury.

PMID- 22656660
TI  - The epidemiology of mountain bike park injuries at the Whistler Bike Park,
      British Columbia (BC), Canada.
AB  - OBJECTIVE: To describe the epidemiology of injuries sustained during the 2009
      season at Whistler Mountain Bike Park. METHODS: A retrospective chart review was
      performed of injured bike park cyclists presenting to the Whistler Health Clinic
      between May 16 and October 12, 2009. RESULTS: Of 898 cases, 86% were male (median
      age, 26 years), 68.7% were Canadian, 19.4% required transport by the Whistler
      Bike Patrol, and 8.4% arrived by emergency medical services. Identification of
      1759 specific injury diagnoses was made, including 420 fractures in 382 patients
      (42.5%). Upper extremity fractures predominated (75.4%), 11.2% had a traumatic
      brain injury, and 8.5% were transferred to a higher level of care: 7 by
      helicopter, 62 by ground, and 5 by personal vehicle. Two patients refused
      transfer. CONCLUSIONS: Mountain bikers incurred many injuries with significant
      morbidity while riding in the Whistler Mountain Bike Park in 2009. Although
      exposure information is unavailable, these findings demonstrate serious risks
      associated with this sport and highlight the need for continued research into
      appropriate safety equipment and risk avoidance measures.

PMID- 22656661
TI  - Fatalities from venomous and nonvenomous animals in the United States (1999
      2007).
AB  - OBJECTIVE: To review recent (1999-2007) US mortality data from deaths caused by
      nonvenomous and venomous animals and compare recent data with historic data.
      METHODS: The CDC WONDER Database was queried to return all animal-related
      fatalities between 1999 and 2007. Rates for animal-related fatalities were
      calculated using the estimated 2003 US population. Inclusion criteria included
      all mortalities that were a consequence of bite, contact, attack, or envenomation
      (ICD-10 codes W53-W59 and X20-X29). RESULTS: There were 1802 animal-related
      fatalities with the majority coming from nonvenomous animals (60.4%). The largest
      percentage (36.4%) of animal-related fatalities was attributable to "other
      mammals," which is largely composed of farm animals. Deaths attributable to
      Hymenoptera (hornets, wasps, and bees) have increased during the past 60 years in
      the United States and now account for more than 79 fatalities per year and 28.2%
      of the total animal-related fatalities from 1999 to 2007. Dog-related fatalities
      have increased in the United States, accounting for approximately 28 fatalities
      per year and 13.9% of the total animal-related fatalities. CONCLUSIONS:
      Prevention measures aimed at minimizing injury from animals should be directed at
      certain high-risk groups such as farmworkers, agricultural workers, and parents
      of children with dogs.

PMID- 22656662
TI  - Hyponatremia in an 85-year-old hiker: when depletion plus dilution produces
      delirium.
AB  - We report a case of critical exercise-associated hyponatremia in an 85-year-old
      man, an experienced hiker, during an overnight trek through Yosemite National
      Park. His medical history was significant for mild renal insufficiency, diastolic
      dysfunction, and pulmonary hypertension. He was taking a thiazide diuretic
      (hydrochlorothiazide), without a prior history of an electrolyte imbalance. The
      hiker drank a modest amount of fluid (3 liters) and urinated only once during the
      9-hour descent, from a starting elevation of approximately 3000 meters, before
      the sudden onset of delirium occurred. He was subsequently airlifted to the
      nearest hospital. Initial blood sodium concentration ([Na(+)]) was 120 mEq/L,
      urine [Na(+)] was 21 mEq/L, plasma osmolality was 266 mOsm/kgH(2)O, and urine
      osmolality 364 mOsm/kgH(2)O. The patient did not respond to infusions of normal
      saline, but after an intravenous 20 mg bolus of furosemide, a copious diuresis
      ensued, after which he recovered fully. This case highlights the complexities of
      fluid and sodium homeostasis during prolonged hiking, as the combination of both
      environmental factors (extreme temperatures, altitude, and water and sodium
      availability) and individual factors (hypertension, age) may have all contributed
      to the development of life-threatening exercise-associated hyponatremia. This
      case is unique in that neither the water intoxication model nor the sodium
      depletion model can fully explain the pathophysiologic findings documented in
      this report.

PMID- 22656663
TI  - Effects of cardiopulmonary resuscitation at high altitudes on the physical
      condition of untrained and unacclimatized rescuers.
AB  - OBJECTIVE: The authors experienced a case of prolonged cardiopulmonary
      resuscitation (CPR) on Mount Fuji (3776 m) that demanded strenuous work by the
      rescuers. The objective of this study was to provide information regarding the
      physiologic effects on the rescuers of performing CPR at moderate altitude.
      METHODS: The effects of CPR at 2700 m and 3700 m above sea level on the physical
      condition of the rescuers were studied in 8 male volunteers. RESULTS:
      Cardiopulmonary resuscitation for 5 minutes at 3700 m significantly reduced
      arterial blood oxygen saturation and increased rate-pressure products (P < .05).
      Scores on the Borg scale, a subjective score of fatigue, after CPR action at 2700
      m (P < .05) and 3700 m (P < .01) were higher than the scores at sea level.
      CONCLUSIONS: Prolonged CPR at high altitude exerts a significant physical effect
      upon the condition of rescuers. A role for mechanical devices should be
      considered wherever possible.

PMID- 22656664
TI  - The foundations of wilderness medicine: some historical features.
AB  - The surgeons of the navies of the early days of western civilization--Greece,
      Rome, and the Italian city-states--were most likely the first practitioners of
      recognizable wilderness medicine. The teachings of Hippocrates and Galen ruled
      over the practice of medicine in Europe for centuries, but the steady evolution
      of understanding of the nature and causes of disease was starting to provide a
      useful foundation upon which to build by the turn of the 19th century. By 1800,
      nonetheless, the gap between medical theory and knowledge and the real ability to
      provide effective therapy was still enormous. However, the discovery of
      anesthesia in the 1840s and Joseph Lister's elucidation and application of the
      principles of asepsis in 1865 were major steps forward in the history of
      medicine. Many other improvements in civilian medical care relevant to wilderness
      medicine, though, have come about as a direct result of military medicine having
      to determine how to best keep people alive and well, often in very trying combat
      related circumstances. The advancement of wilderness medicine has been closely
      connected to military exploration/operations throughout history, and not
      surprisingly, this remains in many ways as true today as it was a thousand years
      ago.

PMID- 22656665
TI  - The role of the expedition doctor: lessons from 100 years ago.
AB  - This paper explores the role of the doctor on the expeditions of the heroic age
      of Antarctic exploration. The medical role includes medical screening of
      prospective expedition members, choosing medical equipment so as to maintain a
      balance between being able to cope with any eventuality and the cost and weight
      of equipment and drugs, health screening during an expedition, first aid training
      for field parties without a doctor, and, obviously, treatment of any injury or
      disease that occurs. If injury or illness occurs, the presence of a doctor is of
      great psychological benefit to the expedition. Although medical experience is
      important, it is probably more important that the doctor is a "team member,"
      playing a full part in the expedition's aims, whether these are scientific,
      exploration, or reaching some goal. Most of the lessons learned during these
      expeditions a hundred years ago are just as relevant today.

PMID- 22656666
TI  - Prehospital medical care and the National Ski Patrol.

PMID- 22656667
TI  - Prehospital medical care and the National Ski Patrol: how does outdoor emergency
      care compare to traditional EMS training?
AB  - OBJECTIVE: The purpose of this study was to identify the differences between the
      educational curricula, skill sets, and funds of knowledge required for
      certification as an Outdoor Emergency Care Technician (OEC-T), Emergency Medical
      Technician (EMT), and Emergency Medical Responder (EMR). METHODS: We directly and
      in detail compared topics and skills presented in the OEC-T curriculum with those
      presented in the EMT and EMR education and training curricula. RESULTS: The
      information and skills taught in the OEC-T curriculum are in general more
      extensive than those taught in EMR training but are not equivalent to EMT. The
      OEC-T program has more depth in environmental medical issues, such as altitude
      illness, hyperthermia and hypothermia. Completion of the EMR program is 112 hours
      shorter and constitutes 30% of the duration of the EMT program. Completion of the
      OEC-T program (for certification only and not including additional "on-hill"
      patroller training) is 80 hours shorter and is half the duration of the EMT
      program. CONCLUSIONS: The OEC-T curriculum includes a skill set and fund of
      knowledge that exceeds those of the EMR program, but does not include all the
      knowledge needed for an EMT program. The OEC-T program prepares out-of-hospital
      providers to care for patients in the wilderness, with special emphasis on
      snowsports pathology. The EMT program places a greater emphasis on medical
      disease and emergency medication administration. These differences should be
      considered when determining staffing requirements for agencies caring for
      patients with snowsports pathology.

PMID- 22656668
TI  - Airway obstruction and acute mountain sickness.

PMID- 22656670
TI  - Cyto-histologic agreement in pathologic subtyping of non small cell lung
      carcinoma: review of 602 fine needle aspirates with follow-up surgical specimens
      over a nine year period and analysis of factors underlying failure to subtype.
AB  - BACKGROUND: The differential therapeutic efficacy and toxicity of targeted
      therapies has made subtyping of non-small lung cancer (NSCLC) mandatory. This
      study aimed to review the accuracy of NSCLC subtyping using lung fine needle
      aspirates (FNAs) in two periods (before and after the introduction of targeted
      therapy), checking the reasons for failure and the impact of the use of
      immunohistochemistry (IHC). METHODS: An electronic search retrieved all NSCLC
      FNAs with a corresponding surgical specimen from 2001 to 2009. NSCLC, NOS (not
      otherwise specified) cases from 2005 to 2009 (after targeted therapy) were
      reviewed to determine reasons for failure in subtyping and to further subtype
      based solely on cytomorphology. The number of cases in which IHC was performed
      and the antibodies used were also recorded. RESULTS: Cytohistological agreement
      of 602 lung FNAs (341 adenocarcinomas, 93 squamous cell carcinomas and 168 NSCLC,
      NOS) was achieved in 93.80%. There was a significant decrease in the percentage
      of cases not subtyped in the period after the introduction of targeted therapy
      (35.07% versus 24.57%). Final percentage of cases not subtyped after
      morphological review was 17.03%. IHC was performed in 157 cases, with an
      increased use in recent years. The number of antibodies did not influence the
      overall success in subtyping and an average of 3 markers was used. Most frequent
      antibodies used were TTF-1, CK7, high molecular weight keratin and p63. More than
      half of cases not subtyped even after IHC corresponded to poorly or
      undifferentiated neoplasms in the surgical specimens. For the NSCLC, NOS which
      IHC was not performed, a cell block was produced in 106 cases (75.71%). Review of
      the cell block slides from 2005 to 2009 showed that the majority (70.7%) had
      rare, few or no tumor cells. CONCLUSIONS: Specific subtyping can be achieved in a
      high proportion of lung FNAs with high accuracy. The percentage of NSCLC, NOS has
      significantly decreased in recent years together with a trend for an increased
      use of IHC as well as increased number of cell blocks produced. An average of 3
      IHC markers was used for subtyping and the number of markers did not influence
      the overall subtyping.

PMID- 22656671
TI  - Elastography in the assessment of sentinel lymph nodes prior to dissection.
AB  - OBJECTIVE: Breast cancer starts as a local tumor but can become metastatic and
      spread via the lymph nodes. When the pre-operative assessment of the axillary
      lymph nodes is negative patients generally undergo sentinel node biopsy (SNB),
      followed by a secondary surgical axillary lymph node dissection (ALND) if the SNB
      is positive. The extemporaneous anatomo-pathological analysis of the sentinel
      lymph node enables metastases to be detected and an ALND at the same time of the
      SNB. The goal of this study was to evaluate the added value of ShearWave
      Elastography (SWE), compared with the conventional pre-operative assessment, in
      the screening of sentinel lymph nodes with a high metastatic risk, which could
      then benefit from an extemporaneous anatomo-pathological analysis. PATIENTS AND
      METHODS: Women undergoing breast surgery with SNB were prospectively enrolled.
      Before surgery, they underwent ultrasound and elastography imaging of axillary
      lymph nodes using the SuperSonic Imagine device and its ShearWaveTM elastography
      mode (SWETM). The results obtained were compared to the immunohistochemical
      results for the removed lymph nodes. RESULTS: 65 patients were enrolled. From the
      103 lymph nodes examined by elastography and the 185 lymph nodes removed we were
      able to pair 81; 70 were healthy and 11 were malignant. The stiffness
      measurements (mean and maximal values) were significantly different between the
      healthy and metastatic lymph nodes, (p<0.05). The areas under the ROC curves were
      0.76 (95% confidence interval (CI): 0.58-0.94) and 0.75 (95%CI: 0.55-0.95) for
      the mean and the maximal stiffness, respectively. CONCLUSION: These encouraging
      results show a correlation between the metastatic risk of lymph nodes and their
      increased mean stiffness. Elasticity variables and potential thresholds that seem
      to predict the metastatic status of axillary lymph nodes were identified. If
      confirmed by further larger studies, these results could be useful in clinical
      practice for the identification of lymph nodes at high metastatic risk that could
      benefit from a intra-operative analysis to reduce the number of secondary
      surgical procedures.

PMID- 22656672
TI  - Lung cancer and diesel exhaust: an updated critical review of the occupational
      epidemiology literature.
AB  - A recent review concluded that the evidence from epidemiology studies was
      indeterminate and that additional studies were required to support the diesel
      exhaust-lung cancer hypothesis. This updated review includes seven recent
      studies. Two population-based studies concluded that significant exposure
      response (E-R) trends between cumulative diesel exhaust and lung cancer were
      unlikely to be entirely explained by bias or confounding. Those studies have
      quality data on life-style risk factors, but do not allow definitive conclusions
      because of inconsistent E-R trends, qualitative exposure estimates and exposure
      misclassification (insufficient latency based on job title), and selection bias
      from low participation rates. Non-definitive results are consistent with the
      larger body of population studies. An NCI/NIOSH cohort mortality and nested case
      control study of non-metal miners have some surrogate-based quantitative diesel
      exposure estimates (including highest exposure measured as respirable elemental
      carbon (REC) in the workplace) and smoking histories. The authors concluded that
      diesel exhaust may cause lung cancer. Nonetheless, the results are non-definitive
      because the conclusions are based on E-R patterns where high exposures were
      deleted to achieve significant results, where a posteriori adjustments were made
      to augment results, and where inappropriate adjustments were made for the
      "negative confounding" effects of smoking even though current smoking was not
      associated with diesel exposure and therefore could not be a confounder. Three
      cohort studies of bus drivers and truck drivers are in effect air pollution
      studies without estimates of diesel exhaust exposure and so are not sufficient
      for assessing the lung cancer-diesel exhaust hypothesis. Results from all
      occupational cohort studies with quantitative estimates of exposure have
      limitations, including weak and inconsistent E-R associations that could be
      explained by bias, confounding or chance, exposure misclassification, and often
      inadequate latency. In sum, the weight of evidence is considered inadequate to
      confirm the diesel-lung cancer hypothesis.

PMID- 22656674
TI  - Challenges in pain research.

PMID- 22656673
TI  - Development of ALZET(r) osmotic pump compatible solvent compositions to
      solubilize poorly soluble compounds for preclinical studies.
AB  - CONTEXT: Hydrophilic, non-aqueous solvents are frequently used to solubilize
      poorly water soluble compounds for use in ALZET(r) osmotic pumps used during the
      discovery and preclinical stages. Though these solvents exhibit the potential to
      solubilize several poorly soluble compounds, the solubilized compounds are prone
      to crystallization up on contact with aqueous fluids in vitro and in vivo.
      Crystallization of a compound can potentially cause pain at the release site,
      erratic blood levels, and uneven or delayed pharmacokinetic profiles. OBJECTIVE:
      In this study, we discussed the development of ALZET(r) pump compatible
      hydrophilic, non-aqueous vehicles that solubilized two poorly soluble model
      compounds (ELND006 and ELN 481594) and prevented their crystallization from
      solutions in vitro and in vivo. METHODS: The selected formulations were filled
      into the pumps at three concentrations for each model compound and investigated
      for their compatibility with the pumps and the subcutaneous tissue of mice where
      the pump was inserted. RESULTS AND DISCUSSION: The results showed that the
      formulations were stable physically with no crystallization and chemically with
      no degradation and were compatible with the pump and animal tissue. The plasma
      concentration of ELND006 decreased with time at each dose. The extent of the time
      dependent decrease in ELND006 plasma levels increased as the amount of dose
      delivered increased. This time and dose dependent decrease in ELND006 plasma
      concentrations was attributed to the known auto-induction of hepatic enzymes by
      the compound. In contrast, the plasma concentration of ELN 481594 increased
      significantly at higher dose, likely due to accumulation of the compound.

PMID- 22656675
TI  - Extracorporeal circulation interference on emergence from anesthesia in patients
      submitted to myocardial revascularization.
AB  - BACKGROUND AND OBJECTIVES: Extracorporeal circulation (ECC) may change drug
      pharmacokinetics as well as brain function. The objectives of this study are to
      compare emergence time and postoperative sedation intensity assessed by the
      bispectral index (BIS) and the Ramsay sedation scale in patients undergoing
      myocardial revascularization (MR) with or without ECC. METHOD: Ten patients
      undergoing MR with ECC (ECC group) and 10 with no ECC (no-ECC group) were
      administered with sufentanyl, propofol 2.0 MUg.mL(-1) and pancuronium target
      controlled infusion. After surgery, propofol infusion was reduced to 1 MUg.mL(-1)
      and suspended when extubation was indicated. Patients BIS, Ramsay scale and time
      to wake up were assessed. RESULTS: The ECC group showed lower BIS values
      beginning at 60 minutes after surgery (no-ECC = 66+/-13 and ECC = 53+/-14,
      p=0.01) until 120 minutes after infusion (no-ECC = 85+/-8 and ECC = 73+/-12,
      p=0.02). Sedation level measured by the Ramsay scale was higher in the ECC group
      at 30 minutes after the end of the surgery (no-ECC = 5+/-1 and ECC = 6+/-0,
      p=0.021), at the end of infusion (no-ECC = 5+/-1 and ECC = 6+/-1, p=0.012) and 5
      minutes after the end of infusion (no-ECC = 4+/-1 and ECC = 5+/-0.42, p=0.039).
      Emergence from anesthesia time was higher in the ECC group (no-ECC = 217+/-81 and
      ECC = 319+/-118, p=0.038). CONCLUSIONS: There was a higher intensity of sedation
      after the end of surgery and a longer wake up time in ECC group, suggesting
      changes in the pharmacokinetics of propofol or effects of ECC on central nervous
      system.

PMID- 22656676
TI  - Ropivacaine for unilateral spinal anesthesia; hyperbaric or hypobaric?
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to compare the unilaterality
      of subarachnoid block achieved with hyperbaric and hypobaric ropivacaine.
      METHODS: The prospective, randomized trial was conducted in an orthopedics
      surgical suite. In all, 60 ASA I-III patients scheduled for elective total knee
      arthroplasty were included in the study. Group Hypo (n=30) received 11.25mg of
      ropivacaine (7.5mg.mL(-1)) + 2mL of distilled water (density at room temperature
      was 0.997) and group Hyper (n=30) received 11.25mg of ropivacaine (7.5mg.mL(-1))
      + 2mL (5mg.mL(-1)) of dextrose (density at room temperature was 1,015). Patients
      in the hyperbaric group were positioned with the operated side down and in the 15
      degrees  Fowler position, versus those in the hypobaric group with the operated
      side facing up and in the 15 degrees  Trendelenburg position. Combined spinal
      epidural anesthesia was performed midline at the L(3-4) lumbar interspace.
      Hemodynamic and spinal block parameters, regression time, success of unilateral
      spinal anesthesia, patient comfort, surgical comfort, surgeon comfort, first
      analgesic requirement time, and adverse effects were assessed. RESULTS: Time to
      reach the T10 dermatome level on the operated side was shorter in group Hyper
      (612.00+/-163.29s) than in group Hypo (763.63+/-208.35s) (p<0.05). Time to 2
      segment regression of the sensory block level on both the operated and non
      operated sides was shorter in group Hypo than in group Hyper. CONCLUSION: Both
      hyperbaric and hypobaric ropivacaine (11.25mg) provided adequate and dependable
      anesthesia for total knee replacement surgery, with a high level of patient and
      surgeon comfort. Hypobaric local anesthetic solutions provide a high level of
      unilateral anesthesia, with rapid recovery of both sensory and motor block, and
      therefore may be preferable in outpatient settings.

PMID- 22656677
TI  - The median effective volume of crystalloid in preventing hypotension in patients
      undergoing cesarean delivery with spinal anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Spinal anesthesia-associated maternal hypotension in
      Cesarean delivery is the most frequent and troublesome complication, posing
      serious risks to mothers and compromising neonatal well-being. The effective
      volume of intravenous crystalloid as the preventive strategy in this context has
      not been estimated. METHODS: Eighty-five parturients with ASA physical status
      I/II undergoing elective Cesarean delivery were screened and 67 eligible women
      were assigned to receive pre-spinal crystalloid loading. Hyperbaric 0.5%
      bupivacaine 2mL (10mg) plus morphine 50MUg was given to all patients. The volume
      of crystalloid was determined by an up-and-down sequential method. The
      crystalloid was infused at a rate of 100-150mL.min(-1) prior to the spinal
      anesthetic injection. The initial volume of crystalloid was 5mL.kg(-1). Volume
      effect data were fitted to a sigmoidal maximum efficacy model and the median
      effective volume (EV(50)) and corresponding 95% confidence interval (95% CI) were
      estimated using maximum likelihood estimation and logistic regression with
      Firth's correction. RESULTS: A total of 67 subjects completed the study and were
      analyzed. Twenty-eight (41.8%) patients developed hypotension with their systolic
      blood pressure (SBP) decreasing > 20% of baseline. The EV(50) of crystalloid were
      12.6mL.kg(-1) (95% CI, 11.6 to 14.8mL.kg(-1)). With Firth's correction, the
      pooled probability of an effective preventive volume of crystalloid at 13mL.kg(
      1) was 50.2% (95% CI, 30% to 83.1%). CONCLUSIONS: The estimated EV(50) of the
      preloaded crystalloid required to prevent spinal anesthesia-induced hypotension
      in a Cesarean section is, approximately, 13mL.kg(-1). However, prophylactic or
      therapeutic vasoconstrictors should also be prepared and administered at an
      appropriate time.

PMID- 22656678
TI  - A comparative study of non-lipid nanoemulsion of propofol with solutol and
      propofol emulsion with lecithin.
AB  - BACKGROUND AND OBJECTIVES: Some formulations have been proposed to reduce the
      adverse reactions due to the lipid emulsion containing soybean oil used as
      propofol carrier. This study for endoscopy sedation was aimed at evaluating and
      comparing the safety, effectiveness and adverse effects of the use of propofol
      nanoemulsion compared to propofol currently commercialized. METHOD: In this
      prospective study, 150 patients were submitted to upper digestive endoscopy.
      These patients were allocated into two groups: the control group (CONT Group;
      n=75) and the nanoemulsion group (NE Group; n=75). HR, SBP, DBP, SpO(2) and BIS
      (which is considered to be appropriate between 65 and 75 during procedure) were
      monitored. Gender, age, weight, height, BMI, ASA physical status, times and doses
      were analyzed, as well as adverse effects (phlogistic signs and pain on
      injection, apnea, nausea/vomiting) and alterations in monitoring variables. A p
      value < 0.05 was considered significant. RESULTS: The groups had similar results
      concerning anthropometric data and physical status. None of the patients
      developed apnea or presented phlogistic signs in the injection site. The
      incidence of pain on injection in the CONT Group was 82.7% and 53.3% in the NE
      Group (p<0.001), and the incidence of nausea and vomiting was 10.7% in the CONT
      Group and 2.7% in the NE Group (p>0.05). The times, induction doses and the SBP
      and DBP values at the end of examination and at the moment of discharge from the
      PACU were lower in the NE Group (p<0.05). CONCLUSIONS: Lipid propofol and
      propofol nanoemulsion were equivalent concerning effectiveness, safety and
      adverse effects in the doses used. There was a lower incidence of pain on
      injection in the nanoemulsion formulation.

PMID- 22656679
TI  - Assessment of anesthesiologists' rapid sequence induction technique in an
      university hospital.
AB  - BACKGROUND AND OBJECTIVES: The induction of the general anesthesia in patients on
      "a full stomach" can result in regurgitation of the gastric content and pulmonary
      aspiration. The function of the rapid sequence induction (RSI) is to minimize the
      time interval between the loss of the airway protection reflexes and tracheal
      intubation tube balloon. The objective of this study was to evaluate the rapid
      sequence induction among the anesthesiologists of the Sao Paulo Hospital.
      METHODS: The participants answered the questionnaire voluntarily and anonymously,
      after signed consent. The questionnaire consisted of 60 questions about the
      fundamental points of the RSI. The questions were divided in pre-oxygenation,
      circuits, drugs used in the induction (opioids, hypnotics, neuromuscular
      blockers), cricoid pressure techniques, intubation and difficult intubation.
      RESULTS: Seventy-five questionnaires were applied and 22 were discarded due to
      incomplete answering. All anesthesiologists always declare doing pre-oxygenation
      and administering opioid, hypnotic, and neuromuscular blocker. Most use fentanyl
      (83%), propofol (74.5%) and succinylcoline (68.6%). All anesthesiologists apply
      cricoid pressure. Most did not know the correct pressure to be applied on the
      cricoid cartilage. Intubation failures have already occurred with 71.7% of
      anesthesiologists and with 40%, the regurgitation. When faced with an unexpected
      difficult intubation, anesthesiologists ask for the laryngeal mask (35.5%).
      CONCLUSIONS: This study showed a broad individual variety of the RSI technique, a
      fact already reported by different authors. The difficulty in establishing a RSI
      protocol can be attributed to constant evidence that science provides us, where
      updating over the years becomes good medical practice.

PMID- 22656680
TI  - Use of volatile anesthetics in extracorporeal circulation.
AB  - BACKGROUND AND OBJECTIVES: The use of volatile anesthetics in cardiac surgery is
      not recent. Since the introduction of halothane in clinical practice, several
      cardiac surgery centers started to use these anesthetics constantly. CONTENT: In
      the last years a great number of studies have shown that the volatile anesthetics
      have a protecting effect against myocardial ischemic dysfunction. Experimental
      evidences have shown that the halogenated anesthetics have cardioprotective
      effects that cannot be only explained by coronary flow alterations or by the
      balance between myocardium available and consumed oxygen. In addition to that,
      the use of volatile anesthetics during extracorporeal circulation (ECC) in
      cardiac surgery plays an important role. Recent studies have proven that these
      agents have cardioprotective properties and produce better results when the
      volatile anesthetic is used during the whole surgery procedure, including ECC.
      The use of halogenated anesthetics through calibrated vaporizers adapted to the
      ECC circuit via oxygenator membranes has become popular. Therefore, the
      professionals involved such as anesthesiologists and perfusionists should learn
      specifics in order to solve possible doubts.

PMID- 22656681
TI  - Clinical and demographic profile of anesthesiologists using alcohol and other
      drugs under treatment in a pioneering program in Brazil.
AB  - BACKGROUND AND OBJECTIVES: Anesthesiologists are the majority in impaired
      physician programs that assist physicians who abuse psychoactive substances. The
      aim of this paper is to show a descriptive study about the clinical and
      sociodemographic profile of a sample of chemically dependent anesthesiologists
      treated in a reference program. In addition, the objective is to cite the
      psychiatric comorbities, the most frequently used drugs and the psychosocial and
      professional repercussions of substance abuse. METHOD: A cross-sectional and
      prospective study was conducted, and a socio-occupational questionnaire and a
      structured interview were carried out to diagnose mental and psychoactive
      substance use disorders, according to the International Classification of
      Diseases (the ICD-10). The questionnaire and the structured interview were
      carried out by two skilled researchers. RESULTS: Fifty-seven anesthesiologists
      were interviewed. Most of them were male (77.2%), and the mean age was 36.1 years
      (SD=8.5%). A high prevalence of abuse of opioid (59.6%), benzodiazepine (3.1%)
      and alcohol (35.1%) was observed. Opioid users sought treatment earlier than
      other substance users and usually they were under pressure from their colleagues
      and the Regional Council of Medicine. The incidence of drug abuse for self
      medication was high in this subgroup. CONCLUSIONS: Anesthesiologists may present
      a different profile concerning the risks of opioid use. Opioid abuse usually
      begins during medical residency or during the first years of clinical practice,
      which supports the hypothesis that addiction to opioids is an occupational issue
      among anesthesiologists.

PMID- 22656682
TI  - Risk factor for intraoperative awareness.
AB  - BACKGROUND AND OBJECTIVES: The intraoperative awareness is an adverse event in
      the general anesthesia, and may occur in approximately 20,000 cases per year,
      which justifies the study of the risk factors for this event. The objective of
      this study was to review this subject in order to reduce the incidence of
      intraoperative awareness and psychological sequelae incurring from this incident,
      which may result in post-traumatic stress disorder with negative repercussions on
      the surgical patient social, psychic and functional development. CONTENT: It was
      conducted a review of the intraoperative awareness assessing its different phases
      during general anesthesia such as dreaming, wakefulness, explicit and implicit
      memory, as well as the analysis, consequences and prevention of its main related
      factors. CONCLUSIONS: The reduction of awareness incidence during anesthesia is
      related to the anesthesiologist improved scientific and technical performance,
      involving issues such as monitoring, comprehension of the anesthesia activity
      components, hypnotic and analgesic drugs, neuromuscular blocking agents,
      autonomic and motor reflex control, in addition to the risk factors involved in
      this event.

PMID- 22656683
TI  - Anesthetic drug abuse by anesthesiologists.
AB  - BACKGROUND AND OBJECTIVES: Physicians has a slightly higher rate of psychoactive
      substance use when compared to the population in general. Anesthesiology is one
      of the most affected medicine specialties, especially due to overwork and easier
      access to drugs. This paper aims to carry out a literature review on the topic.
      Therefore, research was conducted by searching topic-related keywords on papers
      from the last 30 years available on MEDLINE. CONTENT: Despite the fact that
      alcohol abuse is the most common among anesthesiologists, the abuse of anesthetic
      agents causes more concern, due to its high dependence potential and
      consequences, which are often fatal. The most widely used drugs are opioids
      (fentanyl and sufentanil), propofol and inhalational anesthetics. Young
      professionals are the most affected. Among the consequences of drug abuse are
      workplace absence and even death. The return to operating rooms seems to increase
      the risk of relapse. In Europe and in the USA there are specialized treatment
      programs for the middle class, as well as preventive measures, such as strict
      control of drugs and identification of professionals at high risk of abuse. In
      Brazil, Anesthesiology is the second medicine specialty with most drug addicts,
      but the topic has not been much studied and there are few specialized programs in
      the field. CONCLUSIONS: Substance abuse by anesthesiologists is an issue that
      needs to be discussed further, especially due to the possibility of severe
      consequences for professionals and patients.

PMID- 22656684
TI  - Caffeine in the treatment of pain.
AB  - BACKGROUND AND OBJECTIVES: Caffeine is a widely used substance with effects on
      several systems, presenting characteristic of pharmacokinetic and pharmacodynamic
      which cause interactions with several drugs. This study's objective is to review
      the effects caused by caffeine. CONTENT: This review assesses the caffeine
      pharmacology, its action mechanisms, indications, contraindications, doses,
      interactions and adverse effects. CONCLUSIONS: There are insufficient double
      blind randomized controlled studies that assess the analgesic effect of caffeine
      on several painful syndromes. Patients presenting chronic pain need caution when
      it comes to tolerance development, abstinence and drug interaction from chronic
      caffeine use.

PMID- 22656685
TI  - Consciously transfusion of blood products. Systematic review of indicative
      factors for blood components infusion's trigger.
AB  - BACKGROUND AND OBJECTIVES: With the surgical and anesthetic technology advance
      the indications for intervention are expanding, as well as the need for blood
      transfusions. Because of its great scientific value, the content to be exposed is
      subject for endless discussions that provide different guidelines in various
      clinical and laboratory aspects. The objective of this review is to determine the
      clinical, laboratorial, and monitoring signs that should guide blood transfusion
      initiation, avoiding any risk and unnecessary use of resources, as well as the
      delay on starting therapy, determining tissue hypoxia and its corollaries.
      CONTENT: Scientific articles of clinical trials and reviews were used to range
      various subjects approached in the present content. These subjects were divided
      according to clinical and laboratorial aspects. Once the described search
      finished, 2,608 papers were identified, but only 17 original references were
      selected by inclusion criteria. CONCLUSIONS: Literature is unclear about clinical
      criteria on the ideal moment to begin the transfusion therapy in order to
      optimize the relations risk/ and cost/benefit. Studies show that there is no
      significant difference of oxygen supply (O(2)) in a comparison of hemoglobin (Hb)
      levels between 6 and 10g.dL(-1), mainly by reduced blood viscosity, facilitating
      the vascular flow to tissues. However, there is a tendency to recommend the
      transfusion trigger (TT) when it reaches low values as 6-7g.dL(-1). This same
      tendency indicates that red blood cells should never be administered with Hb
      levels > 10g.dL(-1), except in special situations.

PMID- 22656686
TI  - Anesthesia for ex utero intrapartum treatment (EXIT procedure) in fetus with
      prenatal diagnosis of oral and cervical malformations: case reports.
AB  - BACKGROUND AND OBJECTIVES: Fetus prenatally diagnosed with neck tumors, or with
      any other disease that obstructs the airways, should not be treated
      conventionally, as the assistant physician has to face two challenges right after
      the infant's delivery: the limited time to establish the access to the
      potentially difficult airways and the lack of anesthesia of the neonate in case
      of instrumentation of the airways. The ex utero intrapartum treatment, i.e., the
      EXIT procedure consists of maintaining the fetoplacental circulation during the
      cesarean section, until the airways of the fetus be secured. CASE REPORTS: Female
      patient, 37 years old, G3P2, 38 weeks pregnant, having polyhydramnios and fetus
      diagnosed with large cervical masses by prenatal ultrasound. A cesarean section
      was performed using the EXIT procedure to enable safe access to the infant's
      airways. After hysterotomy, the fetus was intubated by direct laryngoscopy. The
      neonate was immediately transferred to another operating room, where cervical
      tumor resection of the neck tumor and tracheostomy were successfully performed.
      Female patient, 27 years old, G3P1A1, 32 weeks pregnant, whose fetus was
      prenatally diagnosed with a large oral tumor. As the tumor obstructed the fetus'
      airways, a tracheostomy was performed when the fetus underwent EXIT procedure. It
      was then possible to use direct laryngoscopy for neonate intubation. The fetus
      underwent tumor resection and was sent to the Neonatal Intensive Care Unit.
      CONCLUSIONS: Reports describe the successful use of general anesthesia with
      isoflurane for cesarean delivery followed by the EXIT procedure in fetus
      diagnosed with tumors obstructing the airways.

PMID- 22656687
TI  - Case report: anesthesia in patients with asphyxiating thoracic dystrophy: Jeune
      syndrome.
AB  - BACKGROUND AND OBJECTIVES: Jeune Syndrome or Asphyxiating Thoracic Dystrophy is a
      recessive autosomal disease. This syndrome is characterized by a bone dysplasia
      with varied abnormalities: thoracic, pancreatic, cardiac, hepatic, renal and
      retinal. Patients' age when the clinical condition is experienced correlates with
      the disease severity. These patients experience polychondrodystrophy with large,
      short, horizontal ribs and irregular costochondral junctions resulting in a rigid
      and reduced thoracic cage with varied respiratory injury level. CASE REPORT: Male
      patient, 4 months-old, 7kg, suffering with Asphyxiating Thoracic Dystrophy,
      intubated and presented with reduced thoracic cage. Echocardiogram: mild
      pulmonary hypertension. Chest tomography: pulmonary hypoplasia. Patient submitted
      to bilateral thoracoplasty and thoracotomy with general anesthesia. Anesthesia
      maintenance: sufentanil e sevoflurane continuous infusion. Ventilation
      parameters: pressure-cycled mechanical ventilation. Thorax opening provided
      improvement of the ventilation parameters, but after thoracic prosthesis
      placement, ventilation was limited. Reduction of the thoracic prosthesis was
      considered with consequent improvement of ventilation. CONCLUSIONS: Diagnosis of
      all present abnormalities is essential for the correct anesthetic management.
      Observation was necessary to adequate pre- and post-thoracotomy/thoracoplasty
      ventilation and to maintain patient hemodynamically stable. Pressure-cycled
      mechanical ventilation is the most adequate type of ventilation to overcome the
      mechanical barrier. In the intraoperative setting, the ideal is to maintain the
      inspiratory pressure peak as low as possible to minimize the risk of barotrauma,
      venous return impairment and reduced cardiac output.

PMID- 22656688
TI  - Fire in the surgical center.
AB  - BACKGROUND AND OBJECTIVES: There are several factors in operating rooms that
      increase the risk of fire. Besides being an oxygen-enriched environment, it
      contains combustible materials and equipment with available ignition sources.
      Although fires in operating rooms are a relatively rare event, the consequences
      are potentially serious and mostly avoidable. We present a case report of a fire
      occurring in the surgical drape during a blepharoplasty in which oxygen was
      supplemented by nasal catheter. CASE REPORT: Female patient, 52-years old,
      without comorbidities, admitted to hospital for a bilateral blepharoplasty. After
      monitoring and venoclysis, the patient underwent intravenous sedation and
      additional oxygen given via spectacle-type catheter at a flow rate of4 L.min(-1),
      followed by local anesthesia in the eyelids. During surgery, the use of electric
      scalpel provoked combustion in the surgical drapes and burns on the patient's
      face. CONCLUSIONS: Anesthesiologists play an important role preventing fire in
      operating rooms, as they can recognize possible ignition sources and rationally
      administer the oxygen, especially in open systems. The first step toward
      prevention is to be constantly aware of potential fire.

PMID- 22656689
TI  - Postoperative residual paralysis.

PMID- 22656690
TI  - Nitrous oxide use in children.

PMID- 22656691
TI  - Decidual vasculopathy and adverse perinatal outcome in preeclamptic pregnancy.
AB  - OBJECTIVE: Decidual vasculopathy (DV) describes pathological findings seen in the
      spiral arteries in preeclampsia (PE). Morphologically, DV is characterized by
      fibrinoid necrosis and foamy macrophages within the vessel walls. The impact of
      the lesions on clinical outcome and placental pathology is unclear. We compared
      cases with DV to cases without these lesions on clinical outcome and placental
      histology in PE. STUDY DESIGN: Placental sections from 107 patients admitted with
      PE at the Radboud University Nijmegen Medical Centre, during the years 1995-2000,
      were analyzed. 25 cases were excluded due to incomplete records or multiple
      pregnancy. Cases with DV (n = 41) and without DV (n = 41) were compared for
      various clinical and placental histological parameters, using Mann-Whitney test.
      P-value < 0.05 was considered significant. RESULTS: Clinically, DV related to
      higher diastolic blood pressure, shorter gestational age, lower birth weight and
      lower umbilical artery pH. Histologically, DV related to more accelerated villous
      maturity and perivascular inflammatory cell infiltration. No differences were
      found in maternal biochemical variables (protein-to-creatinine ratio,
      constituents of HELLP syndrome), fetal-maternal interface parameters (placenta
      weight, infarctions, hematoma, calcifications), or neonatal outcome measures
      (birth weight centile, APGAR scores, and perinatal death). CONCLUSIONS: In PE,
      the presence of DV related to placental accelerated villous maturity,
      perivascular inflammatory cell infiltration, and adverse maternal and fetal
      outcome without affecting neonatal survival. Whether or not DV results from or
      raises the risk on severe preeclampsia remains to be elucidated.

PMID- 22656693
TI  - Martek instruments, inc.

PMID- 22656694
TI  - The Reaction is Purely Chemical.

PMID- 22656696
TI  - How many PMNs?

PMID- 22656692
TI  - P22 viral capsids as nanocomposite high-relaxivity MRI contrast agents.
AB  - Attachment of multiple chelated Gd(3+) ions to the interior of bacteriophage P22
      viral capsids affords nanoscale MRI contrast agents with extremely high
      relaxivity values. Highly fenestrated "wiffleball" morphology is unique to P22
      and assures water exchange between the environment and interior cavity of the
      capsid. The cavity of P22 "wiffleball" was functionalized with a branched
      oligomer comprising multiple DTPA-Gd complexes resulting in an impressive payload
      of 1,900 Gd(3+) ions inside each 64 nm capsid. High relaxivities of r(1,ionic) =
      21.7 mM(-1) s(-1) and r(1,particle) = 41,300 mM(-1) s(-1) at 298 K, 0.65 T (28
      MHz) are reported, with r(1)/r(2) ratio of 0.80 and optimized rotational
      correlation time for this system. Specific design modifications are suggested for
      future improvements of viral capsid-based MRI contrast agents directed toward
      clinical translation.

PMID- 22656698
TI  - Errata".

PMID- 22656697
TI  - An expanding experience. . .

PMID- 22656699
TI  - Five continuing crises at EPA.

PMID- 22656700
TI  - American chemical society sales office.

PMID- 22656701
TI  - States.

PMID- 22656702
TI  - Washington.

PMID- 22656703
TI  - Technology.

PMID- 22656705
TI  - Industry.

PMID- 22656704
TI  - Science.

PMID- 22656707
TI  - OUTLOOK Monitoring report. Personal monitors.

PMID- 22656706
TI  - Man and molecules.

PMID- 22656708
TI  - Restoration of aquifers.

PMID- 22656709
TI  - Clean Water Act revisited.

PMID- 22656710
TI  - Tunable diode laser systems for measuring trace gases intropospheric air.

PMID- 22656711
TI  - Activated sludge:.

PMID- 22656713
TI  - Data collector and reporter.

PMID- 22656712
TI  - International pollution Control costs of coal-fired power plants.

PMID- 22656714
TI  - Electric power research institute.

PMID- 22656715
TI  - Normandeau associates, inc.

PMID- 22656717
TI  - Water supply and sanitation in developing countries.

PMID- 22656716
TI  - Water for trace analysis.

PMID- 22656719
TI  - Courses.

PMID- 22656720
TI  - International.

PMID- 22656722
TI  - professional consulting services directory.

PMID- 22656723
TI  - Classified section.

PMID- 22656724
TI  - Re: Mauro Gacci, Giovanni Corona, Matteo Salvi, et al. A systematic review and
      meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in
      combination with alpha-blockers for lower urinary tract symptoms due to benign
      prostatic hyperplasia. Eur Urol 2012;61:994-1003.

PMID- 22656725
TI  - Effect of soil parameters on the kinetics of the displacement of Fe from FeEDDHA
      chelates by Cu.
AB  - In soil application, o,o-FeEDDHA (iron (3+) ethylene diamine-N,N'-bis(2-hydroxy
      phenyl acetic acid) complex) is the active ingredient of FeEDDHA chelate-based Fe
      fertilizers. The effectiveness of o,o-FeEDDHA is potentially compromised by the
      displacement of Fe from FeEDDHA by Cu. The actual impact of Cu competition is
      codetermined by the kinetics of the displacement reaction. In this study, the
      influence of soil parameters on the displacement kinetics has been examined in
      goethite suspensions. The displacement reaction predominantly takes place on the
      reactive surface rather than in solution. The rate at which the o,o-FeEDDHA
      concentration declined depended on the available reactive surface area, the Cu
      loading, and the FeEDDHA loading. Soil factors reducing FeEDDHA adsorption (high
      ionic strength, humic acid adsorption onto the goethite surface, and monovalent
      instead of divalent cations in the electrolyte) decreased the displacement rate.
      For meso o,o-FeEDDHA, the displacement rate equation was derived, which is first
      order in FeEDDHA loading and half order in Cu loading. For soil conditions, the
      equation can be simplified to an exponential decay function in meso o,o-FeEDDHA
      solution concentration.

PMID- 22656857
TI  - Determination of absolute configuration of salvic acid, an ent-labdane from
      Eupatorium salvia, by vibrational circular dichroism.
AB  - The relative stereochemistry at C13 and the absolute configuration of salvic
      acid, a constituent of the leaves of Eupatorium salvia, were established as the
      13-(R)-ent-labdane 1. The results follow from vibrational circular dichroism
      measurements of the derived O-methyl ether methyl ester 3 which were compared to
      DFT B3LYP/DGDZVP calculated spectra. The relative stereochemistry of salvic acid
      at C13 was independently verified by single crystal X-ray diffraction
      measurements of 1, and of its derived diol 4.

PMID- 22656859
TI  - Conversion of a cyclotriphosphazene to a cyclohexaphosphazene by ring expansion.
AB  - Deprotonation of a cyclotriphosphazene with a tert-butylamino group in the side
      chain results in ring expansion to a very stable, planar cyclohexaphosphazene
      derivative that still contains eight P-Cl bonds suitable for forming
      macromolecular structures.

PMID- 22656860
TI  - A region at the C-terminus of the Escherichia coli global transcription factor
      FNR negatively mediates its degradation by the ClpXP protease.
AB  - The anaerobic global regulator FNR from Escherichia coli is a [4Fe-4S](2+)
      cluster-containing dimer that is inactivated by O(2) through disruption of the Fe
      S cluster and conversion to the monomeric apoprotein. It was shown that apo-FNR
      is subject to ClpXP proteolysis, and two recognition sites, amino acids 5-11 and
      amino acids 249 and 250, are responsible for targeting FNR to the protease.
      However, how the exposure of these sites is mediated such that only apo-FNR is
      recognized by the ClpXP protease and is degraded in a regulated manner so that a
      sufficient and similar FNR level is maintained in both anaerobic and aerobic
      conditions is unknown. To investigate this, we performed three-alanine scanning
      on amino acids 2-19 and 236-250 that are in the proximity of the two ClpXP
      recognition sites, and their functions remain unknown. We found that three
      alanine substitution of residues 239-241 (LAQ239-241A(3)) and 242-244 (LAG242
      244A(3)) caused reduced FNR protein levels, transcription activities, and growth
      rates under anaerobic conditions. In vivo degradation assays demonstrated that
      these mutants were degraded significantly faster than the wild type (WT), and
      either deletion of clpXP or blocking the ClpXP recognition site of amino acids
      249 and 250 stabilizes these proteins. Circular dichroism analysis revealed that
      introduction of LAQ239-241A(3) caused conformational changes with a significant
      loss of secondary structures in both WT and an O(2) stable FNR dimer, FNR D154A.
      We propose that the region of amino acids 239-244 plays a negative role in the
      proteolysis of FNR by promoting a structural fold that limits the exposure of the
      proximal ClpXP site to the protease.

PMID- 22656862
TI  - Testosterone replacement therapy in reversing "andropause": what is the proof-of
      principle?
AB  - Abstract   Testosterone replacement therapy is often equated with the macho male
      physique and virility and is viewed by some as an antiaging tonic. The growth in
      testosterone's reputation and its increased use by men of all ages has seemed to
      outpace the scientific evidences. This review will aim to examine the uncertainty
      regarding the nature and the clinical importance of the age-related reduction in
      the testosterone levels. Considerations will be given both to clinical symptoms,
      biochemical and clinical diagnostic criteria, and to the risk-to-benefit ratio of
      reversing late-onset hypogonadism in aging and older men.

PMID- 22656861
TI  - Long-term health-enhancing physical activity in rheumatoid arthritis--the PARA
      2010 study.
AB  - BACKGROUND: People with rheumatoid arthritis (RA) suffer increased risk of
      disability andpremature mortality. Health-enhancing physical activity (HEPA)
      could be one importantfactor to reduce this risk. Rising health care costs call
      for the development and evaluation ofnew modes of rehabilitation, including
      physical activity in settings outside the health caresystem. METHODS/DESIGN: This
      cohort study targets 450 patients with RA that do not currently meet HEPA
      recommendations, recruited from six hospitals reporting to the Swedish
      Rheumatology Quality Registers (SRQ). We have developed a two-year real-life
      intervention program including a minimum of twice-weekly circuit training,
      moderately intense physical activity the remaining days of the week and group
      meetings to support behavior change every other week. Our hypothesis is that
      increased physical activity and exercise will improve perceived health, reduce
      pain and fatigue, increase muscle function and aerobic capacity, impact
      psychosocial factors and prevent future cardiovascular events. Research questions
      regard outcomes, retention rates, dose-response matters and the exploration of
      responder characteristics. This protocol outlines recruitment procedure, design,
      assessment methods and the intervention program of the study. DISCUSSION: The
      PARA 2010 project is designed to expand the knowledge on HEPA in RA by a
      progressive approach regarding population, setting, intervention, time frames and
      outcome measures. To our knowledge this is the first long-term HEPA program based
      on Social Cognitive Theory, and performed in a real life environment to
      demonstrate if this new setting can promote increased and maintained physical
      activity in people with RA. TRIAL REGISTRATION NUMBER: ISRCTN25539102.

PMID- 22656863
TI  - The large scale conformational change of the human DPP III-substrate prefers the
      "closed" form.
AB  - Human dipeptidyl peptidase III (DPP III) is a two domain metallo-peptidase from
      the M49 family. The wide interdomain cleft and broad substrate specificity
      suggest that this enzyme could experience significant conformational change. Long
      (>100 ns) molecular dynamics (MD) simulations of DPP III revealed large range
      conformational changes of the protein, suggesting the pre-existing equilibrium
      model for a substrate binding. The binding free energy calculations revealed
      tighter binding of the preferred synthetic substrate Arg-Arg-2-naphtylamide to
      the "closed" than to the "open" DPP III conformation. Our assumption that Asp372
      plays a crucial role in the large scale interdomain closure was proved by the MD
      simulations of the Asp372Ala variant. During the same simulation time, the
      variant remained more "open" than the wild type protein. Apparently, Ala was not
      as efficient as Asp in establishing the interdomain interactions. According to
      the MM-PBSA calculations, the electrostatic component of the free energy of
      solvation turned out to be higher for the "closed" protein than for its less
      compact form. However, the gain in entropy due to water released from the
      interdomain cleft nicely balanced this negative effect.

PMID- 22656858
TI  - Glutathione efflux and cell death.
AB  - SIGNIFICANCE: Glutathione (GSH) depletion is a central signaling event that
      regulates the activation of cell death pathways. GSH depletion is often taken as
      a marker of oxidative stress and thus, as a consequence of its antioxidant
      properties scavenging reactive species of both oxygen and nitrogen (ROS/RNS).
      RECENT ADVANCES: There is increasing evidence demonstrating that GSH loss is an
      active phenomenon regulating the redox signaling events modulating cell death
      activation and progression. CRITICAL ISSUES: In this work, we review the role of
      GSH depletion by its efflux, as an important event regulating alterations in the
      cellular redox balance during cell death independent from oxidative stress and
      ROS/RNS formation. We discuss the mechanisms involved in GSH efflux during cell
      death progression and the redox signaling events by which GSH depletion regulates
      the activation of the cell death machinery. FUTURE DIRECTIONS: The evidence
      summarized here clearly places GSH transport as a central mechanism mediating
      redox signaling during cell death progression. Future studies should be directed
      toward identifying the molecular identity of GSH transporters mediating GSH
      extrusion during cell death, and addressing the lack of sensitive approaches to
      quantify GSH efflux.

PMID- 22656864
TI  - Roles of mitochondria-generated reactive oxygen species on X-ray-induced
      apoptosis in a human hepatocellular carcinoma cell line, HLE.
AB  - HLE, a human hepatocellular carcinoma cell line was transiently transfected with
      normal human MnSOD and MnSOD without a mitochondrial targeting signal (MTS).
      Mitochondrial reactive oxygen species (ROS), lipid peroxidation and apoptosis
      were examined as a function of time following 18.8 Gy X-ray irradiation. Our
      results showed that the level of mitochondrial ROS increased and reached a
      maximum level 2 hours after X-ray irradiation. Authentic MnSOD, but not MnSOD
      lacking MTS, protected against mitochondrial ROS, lipid peroxidation and
      apoptosis. In addition, the levels of mitochondrial ROS were consistently found
      to always correlate with the levels of authentic MnSOD in mitochondria. These
      results suggest that only when MnSOD is located in mitochondria is it efficient
      in protecting against cellular injuries by X-ray irradiation and that
      mitochondria are the critical sites of X-ray-induced cellular oxidative injuries.

PMID- 22656866
TI  - iPixel: a visual content-based and semantic search engine for retrieving
      digitized mammograms by using collective intelligence.
AB  - Nowadays, traditional search engines such as Google, Yahoo and Bing facilitate
      the retrieval of information in the format of images, but the results are not
      always useful for the users. This is mainly due to two problems: (1) the semantic
      keywords are not taken into consideration and (2) it is not always possible to
      establish a query using the image features. This issue has been covered in
      different domains in order to develop content-based image retrieval (CBIR)
      systems. The expert community has focussed their attention on the healthcare
      domain, where a lot of visual information for medical analysis is available. This
      paper provides a solution called iPixel Visual Search Engine, which involves
      semantics and content issues in order to search for digitized mammograms. iPixel
      offers the possibility of retrieving mammogram features using collective
      intelligence and implementing a CBIR algorithm. Our proposal compares not only
      features with similar semantic meaning, but also visual features. In this sense,
      the comparisons are made in different ways: by the number of regions per image,
      by maximum and minimum size of regions per image and by average intensity level
      of each region. iPixel Visual Search Engine supports the medical community in
      differential diagnoses related to the diseases of the breast. The iPixel Visual
      Search Engine has been validated by experts in the healthcare domain, such as
      radiologists, in addition to experts in digital image analysis.

PMID- 22656865
TI  - Short course radiotherapy with simultaneous integrated boost for stage I-II
      breast cancer, early toxicities of a randomized clinical trial.
AB  - BACKGROUND: TomoBreast is a unicenter, non-blinded randomized trial comparing
      conventional radiotherapy (CR) vs. hypofractionated Tomotherapy (TT) for post
      operative treatment of breast cancer. The purpose of the trial is to compare
      whether TT can reduce heart and pulmonary toxicity. We evaluate early toxicities.
      METHODS: The trial started inclusion in May 2007 and reached its recruitment in
      August 2011. Women with stage T1-3N0M0 or T1-2N1M0 breast cancer completely
      resected by tumorectomy (BCS) or by mastectomy (MA) who consented to participate
      were randomized, according to a prescribed computer-generated randomization
      schedule, between control arm of CR 25x2 Gy/5 weeks by tangential fields on
      breast/chest wall, plus supraclavicular-axillary field if node-positive, and
      sequential boost 8x2 Gy/2 weeks if BCS (cumulative dose 66 Gy/7 weeks), versus
      experimental TT arm of 15x2.8 Gy/3 weeks, including nodal areas if node-positive
      and simultaneous integrated boost of 0.6 Gy if BCS (cumulative dose 51 Gy/3
      weeks). Outcomes evaluated were the pulmonary and heart function. Comparison of
      proportions used one-sided Fisher's exact test. RESULTS: By May 2010, 70 patients
      were randomized and had more than 1 year of follow-up. Out of 69 evaluable cases,
      32 were assigned to CR (21 BCS, 11 MA), 37 to TT (20 BCS, 17 MA). Skin toxicity
      of grade >=1 at 2 years was 60% in CR, vs. 30% in TT arm. Heart function showed
      no significant difference for left ventricular ejection fraction at 2 years, CR
      4.8% vs. TT 4.6%. Pulmonary function tests at 2 years showed grade >=1 decline of
      FEV1 in 21% of CR, vs. 15% of TT and decline of DLco in 29% of CR, vs. 7% of TT
      (P = 0.05). CONCLUSIONS: There were no unexpected severe toxicities. Short course
      radiotherapy of the breast with simultaneous integrated boost over 3 weeks proved
      feasible without excess toxicities. Pulmonary tests showed a slight trend in
      favor of Tomotherapy, which will need confirmation with longer follow-up of
      patients. TRIAL REGISTRATION: [corrected] ClinicalTrials.gov NCT00459628.

PMID- 22656867
TI  - Parameter-sweeping techniques for temporal dynamics of neuronal systems: case
      study of Hindmarsh-Rose model.
AB  - BACKGROUND: Development of effective and plausible numerical tools is an
      imperative task for thorough studies of nonlinear dynamics in life science
      applications. RESULTS: We have developed a complementary suite of computational
      tools for two-parameter screening of dynamics in neuronal models. We test a
      'brute-force' effectiveness of neuroscience plausible techniques specifically
      tailored for the examination of temporal characteristics, such duty cycle of
      bursting, interspike interval, spike number deviation in the phenomenological
      Hindmarsh-Rose model of a bursting neuron and compare the results obtained by
      calculus-based tools for evaluations of an entire spectrum of Lyapunov exponents
      broadly employed in studies of nonlinear systems. CONCLUSIONS: We have found that
      the results obtained either way agree exceptionally well, and can identify and
      differentiate between various fine structures of complex dynamics and underlying
      global bifurcations in this exemplary model. Our future planes are to enhance the
      applicability of this computational suite for understanding of polyrhythmic
      bursting patterns and their functional transformations in small networks.

PMID- 22656868
TI  - What can be learned from China's health system?

PMID- 22656869
TI  - Drug control in marginalised communities.

PMID- 22656870
TI  - The Royal College of Physicians of London roars.

PMID- 22656871
TI  - Pain control--a basic kindness.

PMID- 22656872
TI  - To screen or not to screen for prostate cancer?

PMID- 22656873
TI  - Accelerating the global response to reduce maternal mortality.

PMID- 22656874
TI  - Oral cholera vaccine and integrated cholera control in Haiti.

PMID- 22656876
TI  - Sarah Tabrizi: tracking Huntington's disease.

PMID- 22656877
TI  - Trends in child maltreatment.

PMID- 22656878
TI  - Trends in child maltreatment.

PMID- 22656881
TI  - Embryonic stem-cell-derived retinal pigment epithelial cells for macular
      degeneration.

PMID- 22656882
TI  - Embryonic stem-cell-derived retinal pigment epithelial cells for macular
      degeneration.

PMID- 22656883
TI  - International health graduates--career path experience.

PMID- 22656884
TI  - Improving pathology for better cancer care and control in countries of low and
      middle income.

PMID- 22656885
TI  - A musician's dystonia.

PMID- 22656886
TI  - Dendritic cell are able to differentially recognize Sporothrix schenckii antigens
      and promote Th1/Th17 response in vitro.
AB  - Sporotrichosis is a disease caused by the dimorphic fungus Sporothrix schenckii.
      The main clinical manifestations occur in the skin, however the number of
      systemic and visceral cases has increased, especially in immunocompromised
      patients. Dendritic cells (DCs) are highly capable to recognize the fungus
      associated data and translate it into differential T cells responses both in vivo
      and in vitro. Although, the mechanisms involved in the interaction between DCs
      and S. schenckii are not fully elucidated. The present study investigated the
      phenotypic and functional changes in bone marrow dendritic cells (BMDCs)
      stimulated in vitro with the yeast form of S. schenckii or exoantigen (ExoAg) and
      its ability to trigger a cellular immune response in vitro. Our results
      demonstrated that the live yeast of S. schenckii and its exoantigen, at a higher
      dose, were able to activate BMDCs and made them capable of triggering T cell
      responses in vitro. Whereas the yeast group promoted more pronounced IFN-gamma
      production rather than IL-17, the Exo100 group generated similar production of
      both cytokines. The exoantigen stimulus suggests a capability to deviate the
      immune response from an effector Th1 to an inflammatory Th17 response.
      Interestingly, only the Exo100 group promoted the production of IL-6 and a
      significant increase of TGF-beta, in addition to IL-23 production. Interestingly,
      only Exo100 group was capable to promote the production of IL-6 and a significant
      increase on TGF-beta, in addition with IL-23 detection. Our results demonstrated
      the plasticity of DCs in translating the data associated with the fungus S.
      schenckii and ExoAg into differential T cell responses in vitro. The possibility
      of using ex vivo-generated DCs as vaccinal and therapeutic tools for
      sporotrichosis is a challenge for the future.

PMID- 22656887
TI  - Deficiency of the CGRP receptor component RAMP1 attenuates immunosuppression
      during the early phase of septic peritonitis.
AB  - The neuropeptide CGRP contributes to the control of excessive cytokine production
      in endotoxemia models. However, the function of CGRP in sepsis caused by
      infection with viable pathogens is unknown. Here, we show that mice deficient for
      the CGRP receptor component RAMP1 have an improved anti-bacterial defense during
      the early, but not late, phase of polymicrobial septic peritonitis. The
      protective effect of Ramp1-deficiency was associated with reduced levels of IL-10
      in plasma and peritoneal lavage fluid. Consistent with these findings, CGRP
      markedly increased IL-10 production of peritoneal and bone marrow-derived
      macrophages in response to short term stimulation with LPS in vitro. In addition,
      the lack of an intact CGRP receptor resulted in an increased recruitment and
      activation of neutrophils and caused an enhanced release of defensin-alpha1 in
      the peritoneal cavity. Considered together, our results identify the neuropeptide
      CGRP as a crucial immunosuppressive mediator impairing host defense during the
      early, but not late, phase of septic peritonitis.

PMID- 22656888
TI  - Nitric oxide affects immune cells bioenergetics: long-term effects of nitric
      oxide derivatives on leukaemic Jurkat cell metabolism.
AB  - Major advances in dissecting mechanisms of NO-induced down-regulation of the anti
      tumour specific T-cell function have been accomplished during the last decade. In
      this work, we studied the effects of a NO donor (AT38) on leukaemic Jurkat cell
      bioenergetics. Culturing Jurkat cells in the presence of AT38 triggered
      irreversible inhibition of cell respiration, led to the depletion of 50% of the
      intracellular ATP content and induced the arrest of cell proliferation and the
      loss of cell viability. Although a deterioration of the overall metabolic
      activity has been observed, glycolysis was stimulated, as revealed by the
      increase of glucose uptake and lactate accumulation rates as well as by the up
      regulation of GLUT-1 and PFK-1 mRNA levels. In the presence of NO, cell ATP was
      rapidly consumed by energy-requiring apoptosis mechanisms; under a glucose
      concentration of about 12.7mM, cell death was switched from apoptosis into
      necrosis. Exposure of Jurkat cells to DMSO (1%, v/v), SA and AT55, the non-NO
      releasing moiety of AT38, failed to modulate neither cell proliferation nor
      bioenergetics. Thus, as for all NSAIDs, beneficial effects of AT38 on tumour
      regression are accompanied by the suppression of the immune system. We then
      showed that pre-treating Jurkat cells with low concentration of cyclosporine A, a
      blocker of the mitochondrial transition pore, attenuates AT38-induced inhibition
      of cell proliferation and suppresses cell death. Finally, we have studied and
      compared the effects of nitrite and nitrate on Jurkat cells to those of NO and we
      are providing evidence that nitrate, which is considered as a biologically inert
      anion, has a concentration and time-dependent immunosuppressive potential.

PMID- 22656889
TI  - [Interventions to reduce the incidence of falls among elderly patients at acute
      care hospital units].

PMID- 22656890
TI  - Ophthalmic generics--are they really the same?

PMID- 22656891
TI  - Nausea and fluourescein injection speed.

PMID- 22656892
TI  - Internal limiting membrane staining.

PMID- 22656894
TI  - Amblyopia refractive risk factors.

PMID- 22656895
TI  - Aspheric intraocular lenses.

PMID- 22656897
TI  - Bilirubin and microangiopathy.

PMID- 22656899
TI  - Choroidal thickness measurements.

PMID- 22656900
TI  - Macular degeneration genetics.

PMID- 22656902
TI  - Macular edema in premature infants.

PMID- 22656904
TI  - Disc swelling and space flight.

PMID- 22656906
TI  - Ocular duction measurement.

PMID- 22656908
TI  - Bilateral ptosis and Hering's dependence.

PMID- 22656910
TI  - Lacrimal gland pleomorphic adenoma.

PMID- 22656912
TI  - Antimicrobial resistance among Gram-negative bacilli isolated from Latin America:
      results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008
      2010).
AB  - This study updates the frequency and resistance rates of Gram-negative bacilli
      isolated from Latin American medical centers enrolled in the SENTRY Antimicrobial
      Surveillance Program. A total of 12,811 bacterial organisms, including 5704 Gram
      negative bacilli (44.5%), were consecutively collected (1 per patient) between
      January 2008 and December 2010 from 10 Latin American medical centers located in
      Argentina, Brazil, Chile, and Mexico. Antimicrobial susceptibility testing was
      performed and interpreted by the Clinical and Laboratory Standards Institute
      broth microdilution method at a central laboratory. All Gram-negative organisms
      with reduced susceptibility to imipenem or meropenem (MIC, >= 2 MUg/mL) were
      screened for carbapenemase production by the modified Hodge test and by
      polymerase chain reaction. ESBL rates were 18.1%, 12.8%, 23.8%, and 48.4% among
      Escherichia coli and 60.4%, 49.9%, 59.2%, and 33.3% among Klebsiella spp. from
      Argentina, Brazil, Chile, and Mexico, respectively. Meropenem-nonsusceptible
      Klebsiella spp. rate was highest in Brazil (11.1%), followed by Argentina (8.2%),
      Chile (5.0%), and Mexico (0.8%). Klebsiella pneumoniae carbapenemase (KPC)
      producing K. pneumoniae was not detected in 2008, but emerged in 2009 (10
      strains) and increased significantly in 2010 (44; P < 0.0001). bla(KPC-2) was
      detected in 54 (65.9%) of 85 carbapenem-nonsusceptible K. pneumoniae. Meropenem
      nonsusceptible P. aeruginosa was observed in 53.8%, 46.7%, 33.3%, and 28.8% of
      strains from Argentina, Brazil, Chile, and Mexico, respectively. Imipenem
      resistant Acinetobacter spp. rates increased from 6.4%, 12.6%, and 0.0% in the
      1997-1999 period to 84.9%, 71.4%, and 50.0% in 2008-2010 in Argentina, Brazil,
      and Chile, respectively. Oxacillinase (OXA)-producing Acinetobacter spp. was
      documented in Argentina (OXA-23 and -24), Brazil (OXA-23), Chile (OXA-58), and
      Mexico (OXA-24). Only colistin showed >77% overall coverage against the 5 most
      frequently isolated Gram-negative bacilli from Latin American Medical centers
      participating in the SENTRY Program.

PMID- 22656913
TI  - The influence of intrinsic and extrinsic job values on turnover intention among
      continuing care assistants in Nova Scotia.
AB  - This article examines the influence that intrinsic and extrinsic job values have
      on the turnover intention of continuing care assistants (CCAs) who work either in
      home care or facility-based care in Nova Scotia (n = 188). Factor analysis of job
      values identified three latent job values structures: "compensation and
      commitment," "flexibility and opportunity," and "positive work relationships."
      Using binary logistic regression, we examined the predictive utility of these
      factors on two indices of turnover intention. Regression results indicate that,
      in general, job values constructs did not significantly predict turnover
      intention when controlling for demographics and job characteristics. However, a
      trend was found for the "positive work relationships" factor in predicting
      consideration of changing employers. In addition, CCAs who work in facility-based
      care were significantly more likely to have considered leaving their current
      employer. With projected increases in the demand for these workers in both home
      and continuing care, more attention is needed to identify and address factors to
      reduce turnover intention.

PMID- 22656915
TI  - Which components of a primary care affiliated home visiting nurse program are
      associated with disability maintenance/improvement?
AB  - A process evaluation of a primary care affiliated home visiting nurse
      intervention was performed to determine which intervention components were
      associated with disability maintenance/improvement. This secondary analysis (N =
      238) used data recorded in intervention databases and patient interviews among
      community-dwelling elders with disability. Intervention components were examined
      in descriptive, correlational, bivariate, and logistic regression analyses.
      Results demonstrated that two structure components--physician-patient-family
      nurse conference visits and intervention (education) materials--and three process
      components--disease management activities, goal setting, and medication
      management activities--were linked to maintaining/improving activities of daily
      living disability status. Confirmation of these findings may help home care
      nurses to delay disability worsening.

PMID- 22656914
TI  - Tailoring work-life interventions for culturally diverse caregivers of patients
      with traumatic brain injury.
AB  - With the increasing incidence of traumatic brain injury among culturally diverse
      families, there has also been increased attention to the dual demands of
      employment and caregiving. In this article, we contend that culturally diverse
      caregivers are an understudied group of workers. We examine literature to assist
      in conceptualizing the relationship between cultural orientation and caregiving,
      work-life stress, and organizational responses. Implications for strengthening
      the cultural responsiveness of work-life initiatives are discussed.

PMID- 22656916
TI  - Identifying risk of hospital readmission among Medicare aged patients: an
      approach using routinely collected data.
AB  - Readmission provisions in the Patient Protection and Affordable Care Act of March
      2010 have created urgent fiscal accountability requirements for hospitals,
      dependent upon a better understanding of their specific populations, along with
      development of mechanisms to easily identify these at-risk patients. Readmissions
      are disruptive and costly to both patients and the health care system.
      Effectively addressing hospital readmissions among Medicare aged patients offers
      promising targets for resources aimed at improved quality of care for older
      patients. Routinely collected data, accessible via electronic medical records,
      were examined using logistic models of sociodemographic, clinical, and
      utilization factors to identify predictors among patients who required
      rehospitalization within 30 days. Specific comorbidities and discharge care
      orders in this urban, nonprofit hospital had significantly greater odds of
      predicting a Medicare aged patient's risk of readmission within 30 days.

PMID- 22656917
TI  - Lipid digestion as a trigger for supersaturation: evaluation of the impact of
      supersaturation stabilization on the in vitro and in vivo performance of self
      emulsifying drug delivery systems.
AB  - The generation of supersaturation in the gastrointestinal (GI) tract is an
      increasingly popular means of promoting oral absorption for poorly water-soluble
      drugs. The current study examined the impact of changes to the quantities of
      medium-chain (MC) lipid (Captex 300:Capmul MCM), surfactant (Cremophor EL) and
      cosolvent (EtOH), and the addition of polymeric precipitation inhibitors (PPI),
      on supersaturation during the dispersion and digestion of MC self-emulsifying
      drug delivery systems (SEDDS) containing danazol. The data suggest that digestion
      acts as a "trigger" for enhanced supersaturation and that
      solubilization/precipitation behavior is correlated with the degree of
      supersaturation on dispersion (S(M)DISP) or digestion (S(M)DIGEST). The ability
      of the formulation to maintain solubilization in vitro decreased as the S(M) of
      the formulation increased. PPI significantly increased supersaturation
      stabilization and precipitation was inhibited where S(M)DISP < 3.5 and S(M)DIGEST
      < 4. In the presence of polymer, some degree of supersaturation was maintained up
      to S(M)DIGEST ~ 8. Differentiation in the ability of SEDDS to maintain drug
      solubilization stems from the ability to stabilize supersaturation and for MC
      SEDDS, utilization of lower drug loads, higher surfactant levels (balanced
      against increases in S(M)DISP), lower cosolvent and the addition of PPI enhanced
      formulation performance. In vivo studies confirmed the ability of PPI to promote
      drug exposure at moderate drug loads (40% of saturated solubility in the
      formulation). At higher drug loads (80% saturation) and in lipid-free SEDDS, this
      effect was lost, suggesting that the ability of PPIs to stabilize supersaturation
      in vitro may, under some circumstances, overestimate utility in vivo. 

PMID- 22656918
TI  - Nalge SYBRON.

PMID- 22656919
TI  - Carlo erba strumentazione.

PMID- 22656921
TI  - Alcohol fuels from biomass.

PMID- 22656922
TI  - Quality control.

PMID- 22656923
TI  - Drinking water contaminants.

PMID- 22656925
TI  - chrompack.

PMID- 22656924
TI  - The myths of environmental regulation.

PMID- 22656926
TI  - Correction.

PMID- 22656928
TI  - International.

PMID- 22656927
TI  - Artic haze.

PMID- 22656929
TI  - Washington.

PMID- 22656931
TI  - Science.

PMID- 22656930
TI  - States.

PMID- 22656933
TI  - Industry.

PMID- 22656932
TI  - Technology.

PMID- 22656934
TI  - Martek instruments, inc.

PMID- 22656935
TI  - Acid rain: A rapidly shifting scene.

PMID- 22656936
TI  - Van nostrand reinhold.

PMID- 22656937
TI  - The breeder reactor project.

PMID- 22656938
TI  - bioanalytical systems.

PMID- 22656940
TI  - Dionex ion chromatographs.

PMID- 22656939
TI  - High-level radioactive waste.

PMID- 22656941
TI  - FIFRA Update.

PMID- 22656943
TI  - American chemical society.

PMID- 22656942
TI  - Anaerobic biotechnology for industrial wastewater treatment.

PMID- 22656944
TI  - Acid generation in the troposphere by gas-phase chemistry.

PMID- 22656945
TI  - American chemical society.

PMID- 22656946
TI  - Products.

PMID- 22656947
TI  - Literature.

PMID- 22656948
TI  - Orion research.

PMID- 22656951
TI  - American chemical society.

PMID- 22656949
TI  - Electric power research institute.

PMID- 22656952
TI  - Courses.

PMID- 22656954
TI  - International.

PMID- 22656953
TI  - Plant resistance to insects.

PMID- 22656956
TI  - professional consulting services directory.

PMID- 22656957
TI  - Classified section.

PMID- 22656959
TI  - A qualitative exploration of the impact of a 12-week group exercise class for
      those moderately affected with multiple sclerosis.
AB  - PURPOSE: The evidence base to support therapeutic exercise for people with
      multiple sclerosis (MS) is improving; however few studies have considered the
      patients' perspective. This study aimed to explore the experiences and views of
      people moderately affected with MS following participation in a 12-week exercise
      programme. METHOD: Twenty people with MS participated in a group exercise class.
      Subsequently, four men and ten women took part in one of two focus groups. Semi
      structured questions were used to elicit participants' views on the exercise
      class, outcomes from exercise and the exercise class and any perceived
      facilitators or barriers to exercise. Data were analysed using a general
      inductive method. RESULTS: Benefits to participating in exercise for those with
      MS included social support and symptom improvement. Psychosocial factors,
      symptoms and lack of service emerged as exercise barriers. Three inter-related
      themes emerged; (1) The exercise class developed as a bridge to allow
      participants to realise, (2) the benefits of the class, helping them to overcome
      and (3) barriers to exercise. CONCLUSION: Taking part in an exercise class was a
      positive experience for people with MS. Healthcare professionals should work with
      exercise professionals to provide feasible exercise opportunities to help those
      with MS benefit from therapeutic exercise.

PMID- 22656961
TI  - Functional compartmentalisation and regulation of postsynaptic Ca2+ transients in
      inhibitory interneurons.
AB  - Information processing within neural circuits depends largely on the dynamic
      interactions between the principal cells and inhibitory interneurons. It is
      further determined by the efficacy of synaptic transmission between individual
      circuit elements, which is in turn tightly regulated by changes in network
      activity to allow for numerous adaptations to occur at a single synapse.
      Intracellular calcium (Ca2+) is a crucial factor in the regulation of synaptic
      efficacy in neuronal networks. Evidence from high-resolution imaging studies has
      revealed the intricacies of how Ca2+ signalling is organised in the dendrites of
      different cell types. Inhibitory interneurons exhibit a variety of postsynaptic
      Ca2+ mechanisms, which are recruited by distinct activity patterns and are
      responsible for the formation of functionally segregated dendritic Ca2+
      microdomains. Furthermore, postsynaptic Ca2+ signals in these cells not only
      contribute to the induction of synaptic plasticity but also may themselves
      undergo different forms of plastic modifications, depending on the activity
      level. This compartmentalised regulation of postsynaptic Ca2+ signalling may have
      a significant impact on the induction of synaptic plasticity and on single
      interneuron and network computations.

PMID- 22656960
TI  - TRPV1-mediated calcium signal couples with cannabinoid receptors and sodium
      calcium exchangers in rat odontoblasts.
AB  - Odontoblasts are involved in the transduction of stimuli applied to exposed
      dentin. Although expression of thermo/mechano/osmo-sensitive transient receptor
      potential (TRP) channels has been demonstrated, the properties of TRP vanilloid 1
      (TRPV1)-mediated signaling remain to be clarified. We investigated physiological
      and pharmacological properties of TRPV1 and its functional coupling with
      cannabinoid (CB) receptors and Na(+)-Ca(2+) exchangers (NCXs) in odontoblasts.
      Anandamide (AEA), capsaicin (CAP), resiniferatoxin (RF) or low-pH evoked Ca(2+)
      influx. This influx was inhibited by capsazepine (CPZ). Delay in time-to
      activation of TRPV1 channels was observed between application of AEA or CAP and
      increase in [Ca(2+)](i). In the absence of extracellular Ca(2+), however, an
      immediate increase in [Ca(2+)](i) was observed on administration of extracellular
      Ca(2+), followed by activation of TRPV1 channels. Intracellular application of
      CAP elicited inward current via opening of TRPV1 channels faster than
      extracellular application. With extracellular RF application, no time delay was
      observed in either increase in [Ca(2+)](i) or inward current, indicating that
      agonist binding sites are located on both extra- and intracellular domains. KB
      R7943, an NCX inhibitor, yielded an increase in the decay time constant during
      TRPV1-mediated Ca(2+) entry. Increase in [Ca(2+)](i) by CB receptor agonist, 2
      arachidonylglycerol, was inhibited by CB1 receptor antagonist or CPZ, as well as
      by adenylyl cyclase inhibitor. These results showed that TRPV1-mediated Ca(2+)
      entry functionally couples with CB1 receptor activation via cAMP signaling.
      Increased [Ca(2+)](i) by TRPV1 activation was extruded by NCXs. Taken together,
      this suggests that cAMP-mediated CB1-TRPV1 crosstalk and TRPV1-NCX coupling play
      an important role in driving cellular functions following transduction of
      external stimuli to odontoblasts.

PMID- 22657089
TI  - The tyrosine gate as a potential entropic lever in the receptor-binding site of
      the bacterial adhesin FimH.
AB  - Uropathogenic Escherichia coli (UPEC) are the major causative agents of urinary
      tract infections. During infection, UPEC adhere to mannosylated glycoreceptors on
      the urothelium via the FimH adhesin located at the tip of type 1 pili. Synthetic
      FimH antiadhesives such as alkyl and phenyl alpha-D-mannopyranosides are thus
      ideal candidates for the chemical interception of this crucial step in
      pathogenesis. The crystal structures of the FimH lectin domain in its ligand-free
      form and in complexes with eight medium- and high-affinity mannopyranoside
      inhibitors are presented. The thermodynamic profiles of the FimH-inhibitor
      interactions indicate that the binding of FimH to alpha-D-mannopyranose is
      enthalpy-driven and has a negative entropic change. Addition of a hydrophobic
      aglycon influences the binding enthalpy and can induce a favorable entropic
      change. The alleviation of the entropic cost is at least in part explained by
      increased dynamics in the tyrosine gate (Tyr48 and Tyr137) of the FimH receptor
      binding site upon binding of the ligand. Ligands with a phenyl group directly
      linked to the anomeric oxygen of alpha-D-mannose introduce the largest dynamics
      into the Tyr48 side chain, because conjugation with the anomeric oxygen of alpha
      D-mannose forces the aromatic aglycon into a conformation that comes into close
      contact (~2.65 A) with Tyr48. A propargyl group in this position predetermines
      the orientation of the aglycon and significantly decreases affinity. FimH has the
      highest affinity for alpha-D-mannopyranosides substituted with hydrophobic
      aglycons that are compatible in shape and electrostatic properties to the
      tyrosine gate, such as heptyl alpha-D-mannose.

PMID- 22657090
TI  - Improving the cost-effectiveness of cardiovascular disease prevention in
      Australia: a modelling study.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death worldwide. Like
      many countries, Australia is currently changing its guidelines for cardiovascular
      disease prevention from drug treatment for everyone with 'high blood pressure' or
      'high cholesterol', to prevention based on a patient's absolute risk. In this
      research, we model cost-effectiveness of cardiovascular disease prevention with
      blood pressure and lipid drugs in Australia under three different scenarios: (1)
      the true current practice in Australia; (2) prevention as intended under the
      current guidelines; and (3) prevention according to proposed absolute risk
      levels. We consider the implications of changing to absolute risk-based
      cardiovascular disease prevention, for the health of the Australian people and
      for Government health sector expenditure over the long term. METHODS: We evaluate
      cost-effectiveness of statins, diuretics, ACE inhibitors, calcium channel
      blockers and beta-blockers, for Australian men and women, aged 35 to 84 years,
      who have never experienced a heart disease or stroke event. Epidemiological
      changes and health care costs are simulated by age and sex in a discrete time
      Markov model, to determine total impacts on population health and health sector
      costs over the lifetime, from which we derive cost-effectiveness ratios in 2008
      Australian dollars per quality-adjusted life year. RESULTS: Cardiovascular
      disease prevention based on absolute risk is more cost-effective than prevention
      under the current guidelines based on single risk factor thresholds, and is more
      cost-effective than the current practice, which does not follow current clinical
      guidelines. Recommending blood pressure-lowering drugs to everyone with at least
      5% absolute risk and statin drugs to everyone with at least 10% absolute risk,
      can achieve current levels of population health, while saving $5.4 billion for
      the Australian Government over the lifetime of the population. But savings could
      be as high as $7.1 billion if Australia could match the cheaper price of statin
      drugs in New Zealand. CONCLUSIONS: Changing to absolute risk-based cardiovascular
      disease prevention is highly recommended for reducing health sector spending, but
      the Australian Government must also consider measures to reduce the cost of
      statin drugs, over and above the legislated price cuts of November 2010.

PMID- 22657092
TI  - Uptake of Pap smears among women in a large Israeli HMO between 2006 and 2008.
AB  - OBJECTIVES: The Papanicolaou (Pap) smear test is used in many countries as a
      screening procedure for cervical cancer and precancerous lesions. The actual
      uptake of this screening test among women at risk for cervical cancer is unknown.
      The aim of this study was to estimate the percentage of women who are screened by
      Pap smears from the relevant population at risk, and to detect factors that are
      independently associated with uptake of cervical screening. STUDY DESIGN:
      Retrospective database study. METHODS: This study was undertaken at Maccabi
      Healthcare Services (MHS), the second largest publicly funded health maintenance
      organization in Israel. The study population consisted of Israeli women aged 21
      59 years who were insured by MHS between 2006 and 2008. Logistic regression
      analyses were used to determine the independent relationships between immigration
      and socio-economic status and cervical screening. RESULTS: The study population
      included 489,663 women who had a total of 313,602 Pap smears between 2006 and
      2008. Fifty-four percent of the women did not have a Pap smear during the study
      period, 32% had at least one smear, and 14% had at least two smears. Living in a
      low socio-economic neighbourhood and recent immigration were independently and
      negatively associated with screening uptake. CONCLUSION: Despite the clinical
      guidelines and the low costs, many Israeli women who are at risk for cervical
      cancer are not screened.

PMID- 22657093
TI  - Multiple crises and global health: new and necessary frontiers of health
      politics.
AB  - The world economy is entering an era of multiple crises, involving finance, food
      security and global environmental change. This article assesses the implications
      for global public health, describes the contours of post-2007 crises in food
      security and finance, and then briefly indicates the probable health impacts.
      There follows a discussion of the crisis of climate change, one that will unfold
      over a longer time frame but with manifestations that may already be upon us. The
      article then discusses the political economy of responses to these crises, noting
      the formidable obstacles that exist to equitable resolution. The article
      concludes by noting the threat that such crises present to recent progress in
      global health, arguing that global health researchers and practitioners must
      become more familiar with the relevant social processes, and that proposed
      solutions that neglect the continuing importance of the nation-state are
      misdirected.

PMID- 22657091
TI  - Reactive oxygen species and antioxidants in pulmonary hypertension.
AB  - SIGNIFICANCE: Pulmonary hypertension is a devastating disorder without any
      available treatment strategies that satisfactorily promote the survival of
      patients. The identification of new therapeutic strategies to treat patients with
      pulmonary hypertension is warranted. RECENT ADVANCES: Human studies have provided
      evidence that there is increased oxidative stress (lipid peroxidation, protein
      oxidation, DNA oxidation, and the depletion of small-molecule antioxidants) in
      patients with pulmonary hypertension. A variety of compounds with antioxidant
      properties have been shown to have beneficial therapeutic effects in animal
      models of pulmonary hypertension, possibly supporting the hypothesis that
      reactive oxygen species (ROS) are involved in the progression of pulmonary
      hypertension. Thus, understanding the molecular mechanisms of ROS actions could
      contribute to the development of optimal, antioxidant-based therapy for human
      pulmonary hypertension. One such mechanism includes action as a second messenger
      during cell-signaling events, leading to the growth of pulmonary vascular cells
      and right ventricular cells. CRITICAL ISSUES: The molecular mechanisms behind
      promotion of cell signaling for pulmonary vascular cell growth and right
      ventricular hypertrophy by ROS are not well understood. Evidence suggests that
      iron-catalyzed protein carbonylation may be involved. FUTURE DIRECTIONS:
      Understanding precise mechanisms of ROS actions should be useful for designing
      preclinical animal experiments and human clinical trials of the use of
      antioxidants and/or other redox compounds in the treatment of pulmonary
      hypertension.

PMID- 22657094
TI  - Serial observation of an enlarging intracerebral arachnoid cyst.

PMID- 22657095
TI  - Autologous bone marrow mononuclear cell implantation for intracerebral hemorrhage
      a prospective clinical observation.
AB  - BACKGROUND: This study was designed to assess the clinical effect of bone marrow
      mononuclear cells including mesenchymal stem cell (MSCs) in patients with
      intracerebral hemorrhage (ICH). METHODS: One hundred patients were divided into a
      study (n=60) or a control group (n=40). Bone marrow mononuclear cells from the
      same patient were injected to the perihemorrhage area in the base ganglia through
      an intracranial drainage tube 5.9 days after ICH. National Institute Stroke Scale
      (NIHSSS) and Barthel index was used to assess neurologic impairment and daily
      activities, respectively, before and 6 months after intervention. RESULTS: Six
      months after implantation, the NIHSS score in the study group was lower than in
      the control group (10.09 +/- 8.86 vs 14.35 +/- 10.14, P<0.01), whereas the
      Barthel scores were higher (57.39 +/- 23.51 vs 46.90 +/- 20.29, P<0.01).
      Neurological and functional improvement was observed in 52 (86.7%) of the study
      group patients, and in 17 (42.5%) of the control group patients (P=0.001). No
      allergic or other adverse effects were observed in the study group. CONCLUSION:
      Autologous bone marrow mononuclear cell implantation reduced neurological
      impairment and improved activities of daily living in a selected group of ICH
      patients. Further studies are required to ascertain the long-term safety and
      efficacy of this treatment.

PMID- 22657096
TI  - A case of paraneoplastic vasculitic neuropathy associated with gastric cancer.

PMID- 22657097
TI  - Analysis of nonlinear noisy integrate & fire neuron models: blow-up and steady
      states.
AB  - Nonlinear Noisy Leaky Integrate and Fire (NNLIF) models for neurons networks can
      be written as Fokker-Planck-Kolmogorov equations on the probability density of
      neurons, the main parameters in the model being the connectivity of the network
      and the noise. We analyse several aspects of the NNLIF model: the number of
      steady states, a priori estimates, blow-up issues and convergence toward
      equilibrium in the linear case. In particular, for excitatory networks, blow-up
      always occurs for initial data concentrated close to the firing potential. These
      results show how critical is the balance between noise and excitatory/inhibitory
      interactions to the connectivity parameter.AMS Subject Classification:  35K60,
      82C31, 92B20.

PMID- 22657098
TI  - Granulomatous cheilitis: a report of 6 cases and a review of the literature.
AB  - INTRODUCTION: Granulomatous cheilitis (Miescher cheilitis), a condition
      characterized by recurrent swelling of the lips, is the most common
      monosymptomatic form of the Melkersson-Rosenthal syndrome. The aim of this study
      was to study the characteristics of patients diagnosed with granulomatous
      cheilitis at the dermatology department of our hospital over a period of 17
      years. MATERIAL AND METHODS: We performed a descriptive study of patients
      diagnosed with granulomatous cheilitis at our hospital between January 1993 and
      January 2010. RESULTS: The condition was diagnosed in 6 patients (4 women and 2
      men), with a mean age of 49 years at the time of diagnosis. All the patients had
      recurrent swelling of the upper lip and 2 also had swelling in other parts of the
      face. The mean time from the onset of symptoms to the initial visit was
      approximately 16 months. There were no cases of facial palsy, and just 1 patient
      had a fissured tongue. None of the patients developed Crohn disease or any other
      granulomatous disorders during follow-up. CONCLUSIONS: Granulomatous cheilitis is
      a rare disease. None of the patients in our series had gastrointestinal or
      neurologic symptoms. Accordingly, we believe that granulomatous cheilitis is an
      independent orofacial granulomatous disease which most often presents without
      accompanying signs or symptoms.

PMID- 22657100
TI  - Comparison of accessing online databases between physicians and nurses in Taiwan.
AB  - Online databases have been increasingly used as a key resource in the search for
      health information. The current study aims to compare the use patterns of online
      databases between physicians and nurses. A structured questionnaire was mailed to
      physicians and nurses of randomly selected regional hospitals in Taiwan. Valid
      questionnaires with complete answers were collected from 544 physicians and 1,573
      nurses from November 2008 to February 2009. In general, physicians made more use
      of online databases than nurses (p  <  0.001). They more often accessed English
      language online databases (p  <  0.001), including MEDLINE, MD Consult, UpToDate,
      Cochrane Library and ProQuest. On the other hand, nurses accessed Chinese
      language online databases more frequently than physicians (p  <  0.001). Using a
      multivariate logistic regression model to adjust the personal characteristics, we
      found that nurses more often accessed Chinese-language online databases than
      physicians. Physicians used online databases to locate health information the
      most for clinical practice (76.6%), followed by instruction preparation (63.3%),
      and research (57.0%). Nevertheless, nurses used such databases more often for
      class assignments (66.4%) and clinical practice (55.8%). In conclusion, the
      behavior and motivation of access to online databases varied between physicians
      and nurses. Our findings provide evidence in the strategies to enhance the
      accessing of online databases.

PMID- 22657099
TI  - Temporal resolution of autophosphorylation for normal and oncogenic forms of EGFR
      and differential effects of gefitinib.
AB  - Epidermal growth factor receptor (EGFR) is a member of the ErbB family of
      receptor tyrosine kinases (RTK). EGFR overexpression or mutation in many
      different forms of cancers has highlighted its role as an important therapeutic
      target. Gefitinib, the first small molecule inhibitor of EGFR kinase function to
      be approved for the treatment of nonsmall cell lung cancer (NSCLC) by the FDA,
      demonstrates clinical activity primarily in patients with tumors that harbor
      somatic kinase domain mutations in EGFR. Here, we compare wild-type EGFR
      autophosphorylation kinetics to the L834R (also called L858R) EGFR form, one of
      the most common mutations in lung cancer patients. Using rapid chemical quench,
      time-resolved electrospray mass spectrometry (ESI-MS), and Western blot analyses,
      we examined the order of autophosphorylation in wild-type (WT) and L834R EGFR and
      the effect of gefitinib (Iressa) on the phosphorylation of individual tyrosines.
      These studies establish that there is a temporal order of autophosphorylation of
      key tyrosines involved in downstream signaling for WT EGFR and a loss of order
      for the oncogenic L834R mutant. These studies also reveal unique signature
      patterns of drug sensitivity for inhibition of tyrosine autophosphorylation by
      gefitinib: distinct for WT and oncogenic L834R mutant forms of EGFR. Fluorescence
      studies show that for WT EGFR the binding affinity for gefitinib is weaker for
      the phosphorylated protein while for the oncogenic mutant, L834R EGFR, the
      binding affinity of gefitinib is substantially enhanced and likely contributes to
      the efficacy observed clinically. This mechanistic information is important in
      understanding the molecular details underpinning clinical observations as well as
      to aid in the design of more potent and selective EGFR inhibitors.

PMID- 22657101
TI  - A novel approach to control air leaks in complex lung surgery: a retrospective
      review.
AB  - BACKGROUND: Intra-operative air leaks (IOAL) are common complications of
      pulmonary surgery. The post-operative management of air leaks requires a chest
      tube which may lead to longer hospitalization, further medical complications, and
      increased costs. Sealants have been shown to help control intra-operative air
      leaks and studies have demonstrated a reduction in chest tube duration and/or
      length of hospital stay. Nevertheless, systematic reviews have not presented
      sufficient evidence to recommend their general use in lung resection. METHODS:
      One hundred and twenty-one consecutive patients who underwent pulmonary surgery
      with and without Progel(r) Pleural Air Leak Sealant were reviewed
      retrospectively. Intra-operative and 3-months postoperative data were assessed
      for the presence and persistence of air leaks, chest tube duration, the length of
      hospital stay, and complications. RESULTS: Seventy patients (57.9%) had IOAL.
      Thirty-six were treated with Progel in addition to standard intra-operative
      technique (pleural-sealant group; PSG) and 34 patients were treated only with
      standard technique (control group; CG). The percentage of post-operative air
      leaks in the PSG was 11% (1.2% >Grade 2 air leak) compared with 58.8% (6% >Grade
      2 air leak) in the CG (p <0.0001, Leaks graded from 1 = small air leak to 7 =
      large air leak). The median chest tube duration was significantly shorter in the
      PSG compared with the controls (1.0 versus 2.5 days; p < 0.0001). The median
      length of hospital stay was 50% lower in the PSG compared with the control group
      (1.5 versus 3.0 days; p = 0.047). There were no significant differences in
      complications between the two groups. CONCLUSIONS: The results of this single
      center, single surgeon, retrospective review demonstrate a significant reduction
      in IOAL, chest tube duration, and length of hospital stay in the in patients
      treated with Progel when compared with standard intra-operative closure
      management alone. They suggest that the use of a pleural sealant is more
      effective in reducing alveolar air leaks associated with lung resection compared
      with standard closure techniques alone and may result in both an improved
      surgical outcome and a reduction in costs associated with prolonged hospital
      stay.

PMID- 22657102
TI  - Enrichment of denitrifying methanotrophic bacteria for application after direct
      low-temperature anaerobic sewage treatment.
AB  - Despite many advantages of anaerobic sewage treatment over conventional activated
      sludge treatment, it has not yet been applied in temperate zones. This is
      especially because effluent from low-temperature anaerobic treatment contains
      nitrogen and dissolved methane. The presence of nitrogen and methane offers the
      opportunity to develop a reactor in which methane is used as electron donor for
      denitrification. Such a reactor could be used in a new concept for low
      temperature anaerobic sewage treatment, consisting of a UASB-digester system, a
      reactor for denitrification coupled to anaerobic methane oxidation, and a
      nitritation reactor. In the present study denitrifying methanotrophic bacteria
      similar to 'Candidatus Methylomirabilis oxyfera' were enriched. Maximum
      volumetric nitrite consumption rates were 33.5 mg NO(2)(-)-N/Ld (using synthetic
      medium) and 37.8 mg NO(2)(-)-N/Ld (using medium containing effluent from a sewage
      treatment plant), which are similar to the maximum rate reported so far. Though
      the goal was to increase the rates, in both reactors, after reaching these
      maximum rates, volumetric nitrite consumption rates decreased in time. Results
      indicate biomass washout may have significantly decelerated enrichment.
      Therefore, to obtain higher volumetric consumption rates, further research should
      focus on systems with complete biomass retention.

PMID- 22657104
TI  - An innovative numerical approach to resolve the pulse wave velocity in a healthy
      thoracic aorta model.
AB  - Aortic dissection and atherosclerosis are highly fatal diseases. The development
      of both diseases is closely associated with highly complex haemodynamics. Thus,
      in predicting the onset of cardiac disease, it is desirable to obtain a detailed
      understanding of the flowfield characteristics in the human cardiovascular
      circulatory system. Accordingly, in this study, a numerical model of a normal
      human thoracic aorta is constructed using the geometry information obtained from
      a phase-contrast magnetic resonance imaging (PC-MRI) technique. The interaction
      between the blood flow and the vessel wall dynamics is then investigated using a
      coupled fluid-structure interaction (FSI) analysis. The simulations focus
      specifically on the flowfield characteristics and pulse wave velocity (PWV) of
      the blood flow. Instead of using a conventional PC-MRI method to measure PWV, we
      present an innovative application of using the FSI approach to numerically
      resolve PWV for the assessment of wall compliance in a thoracic aorta model. The
      estimated PWV for a normal thoracic aorta agrees well with the results obtained
      via PC-MRI measurement. In addition, simulations which consider the FSI effect
      yield a lower predicted value of the wall shear stress at certain locations in
      the cardiac cycle than models which assume a rigid vessel wall. Consequently, the
      model provides a suitable basis for the future development of more sophisticated
      methods capable of performing the computer-aided analysis of aortic blood flows. 

PMID- 22657103
TI  - Health risk of heavy metals in food crops grown on reclaimed tidal flat soil in
      the Pearl River Estuary, China.
AB  - The health risks of heavy metals to local residents via consumption of food crops
      cultivated in the reclaimed soils of the Pearl River Estuary (PRE) were
      investigated. Soils in the river estuary were found to be significantly
      contaminated with heavy metals, with mean concentrations of Cd, 0.858; Pb, 48.7;
      Cr, 112.4; Cu, 57.3; Zn, 210.8; and Ni, 40.0 mg kg(-1). Rice and root vegetables
      were also polluted severely. The percentages of rice samples that exceeded the
      maximum allowable levels were 94.3, 91.4, 88.6, and 17.1% for Pb, Cr, Cd, and Cu,
      respectively. The accumulation factor (AF) of Cd was the highest compared with
      the other five metals. The total values of the health risk index (HRI) of Cd and
      Cu from all the crops were 3.683 and 1.665, respectively. They exceeded
      considerably the allowable level 1.0. The HRI values of all the metals were
      mostly from rice consumption. These results suggest that more attention should be
      directed to the potential health risks of heavy metals to residents living in the
      tidal flat reclaimed areas.

PMID- 22657105
TI  - Lattice enumeration for inverse molecular design using the signature descriptor.
AB  - We describe an inverse quantitative structure-activity relationship (QSAR)
      framework developed for the design of molecular structures with desired
      properties. This framework uses chemical fragments encoded with a molecular
      descriptor known as a signature. It solves a system of linear constrained
      Diophantine equations to reorganize the fragments into novel molecular
      structures. The method has been previously applied to problems in drug and
      materials design but has inherent computational limitations due to the necessity
      of solving the Diophantine constraints. We propose a new approach to overcome
      these limitations using the Fincke-Pohst algorithm for lattice enumeration. We
      benchmark the new approach against previous results on LFA-1/ICAM-1 inhibitory
      peptides, linear homopolymers, and hydrofluoroether foam blowing agents. Software
      implementing the new approach is available at
      www.cs.otago.ac.nz/homepages/smartin.

PMID- 22657108
TI  - Letter from the editor: Who's at risk for heart disease?

PMID- 22657106
TI  - Conservation and divergence between cytoplasmic and muscle-specific actin capping
      proteins: insights from the crystal structure of cytoplasmic Cap32/34 from
      Dictyostelium discoideum.
AB  - BACKGROUND: Capping protein (CP), also known as CapZ in muscle cells and Cap32/34
      in Dictyostelium discoideum, plays a major role in regulating actin filament
      dynamics. CP is a ubiquitously expressed heterodimer comprising an alpha- and
      beta-subunit. It tightly binds to the fast growing end of actin filaments,
      thereby functioning as a "cap" by blocking the addition and loss of actin
      subunits. Vertebrates contain two somatic variants of CP, one being primarily
      found at the cell periphery of non-muscle tissues while the other is mainly
      localized at the Z-discs of skeletal muscles. RESULTS: To elucidate structural
      and functional differences between cytoplasmic and sarcomercic CP variants, we
      have solved the atomic structure of Cap32/34 (32=beta- and 34=alpha-subunit) from
      the cellular slime mold Dictyostelium at 2.2 A resolution and compared it to that
      of chicken muscle CapZ. The two homologs display a similar overall arrangement
      including the attached alpha-subunit C-terminus (alpha-tentacle) and the flexible
      beta-tentacle. Nevertheless, the structures exhibit marked differences suggesting
      considerable structural flexibility within the alpha-subunit. In the alpha
      subunit we observed a bending motion of the beta-sheet region located opposite to
      the position of the C-terminal beta-tentacle towards the antiparallel helices
      that interconnect the heterodimer. Recently, a two domain twisting attributed
      mainly to the beta-subunit has been reported. At the hinge of these two domains
      Cap32/34 contains an elongated and highly flexible loop, which has been reported
      to be important for the interaction of cytoplasmic CP with actin and might
      contribute to the more dynamic actin-binding of cytoplasmic compared to
      sarcomeric CP (CapZ). CONCLUSIONS: The structure of Cap32/34 from Dictyostelium
      discoideum allowed a detailed analysis and comparison between the cytoplasmic and
      sarcomeric variants of CP. Significant structural flexibility could particularly
      be found within the alpha-subunit, a loop region in the beta-subunit, and the
      surface of the alpha-globule where the amino acid differences between the
      cytoplasmic and sarcomeric mammalian CP are located. Hence, the crystal structure
      of Cap32/34 raises the possibility of different binding behaviours of the CP
      variants toward the barbed end of actin filaments, a feature, which might have
      arisen from adaptation to different environments.

PMID- 22657107
TI  - An extracellular MRI polymeric contrast agent that degrades at physiological pH.
AB  - Macromolecular contrast agents have the potential to assist magnetic resonance
      imaging (MRI) due to their high relaxivity, but are not clinically useful because
      of toxicity due to poor clearance. We have prepared a biodegradable ketal-based
      polymer contrast agent which is designed to degrade rapidly at physiological pH
      by hydrolysis, facilitating renal clearance. In vitro, the agent degraded more
      rapidly at lower pH, with complete fragmentation after 24 h at pH 7.4. In vitro
      relaxivity measurements showed a direct correlation between molecular weight and
      relaxivity. We compared our polymer contrast agent with commercially available
      Magnevist in vivo by MRI imaging, as well as measuring the Gd concentration in
      blood. Our results show that our polymer contrast agent gives a higher contrast
      and intensity in the same organs and areas as Magnevist and is cleared from the
      blood at a similar rate. We aim to improve our polymer contrast agent design to
      develop it for use as a MRI contrast agent, and explore its use as a platform for
      other imaging modalities. 

PMID- 22657109
TI  - Letter from the guest editor: Cardiac imaging.

PMID- 22657110
TI  - Case of the season: Coronary cameral fistula.

PMID- 22657111
TI  - Coronary computed tomography angiography: a practical guide to performance and
      interpretation.

PMID- 22657112
TI  - Evidence for medical management versus revascularization for coronary artery
      disease: guidance from cardiac magnetic resonance imaging and computed
      tomography.

PMID- 22657113
TI  - The complementary roles of radionuclide myocardial perfusion imaging and cardiac
      computed tomography.

PMID- 22657114
TI  - Computed tomography angiography of coronary artery bypass graft grafts.

PMID- 22657115
TI  - Role of multimodality imaging in the diagnosis and treatment of hypertrophic
      cardiomyopathy.

PMID- 22657116
TI  - Cardiac aneurysms, pseudoaneurysms, and diverticula.

PMID- 22657118
TI  - Making complex adult congenital heart disease a little simpler.

PMID- 22657117
TI  - Simple cardiac shunts in adults.

PMID- 22657119
TI  - Whither environmental progress?

PMID- 22657120
TI  - Independent evaluation of monitoring data.

PMID- 22657121
TI  - RCRA reauthorization.

PMID- 22657122
TI  - Health risks from light-duty diesel vehicles.

PMID- 22657123
TI  - PCB contamination in and around New Bedford, Mass.

PMID- 22657124
TI  - Alltech associates, inc.

PMID- 22657125
TI  - ES&Ts 1984 Advisory Board.

PMID- 22657126
TI  - Dionex corporation.

PMID- 22657128
TI  - CetaepsilonmtauepsiloncEta.

PMID- 22657127
TI  - Literature.

PMID- 22657129
TI  - Products.

PMID- 22657130
TI  - professional consulting services directory.

PMID- 22657131
TI  - Equal protection for all.

PMID- 22657132
TI  - Correction.

PMID- 22657133
TI  - NUS Corporation.

PMID- 22657135
TI  - The zimmerman award.

PMID- 22657134
TI  - PCB replacements.

PMID- 22657137
TI  - States.

PMID- 22657136
TI  - International.

PMID- 22657138
TI  - Washington.

PMID- 22657139
TI  - Awards.

PMID- 22657140
TI  - Science.

PMID- 22657142
TI  - Business.

PMID- 22657141
TI  - Technology.

PMID- 22657143
TI  - Forest decline from air pollution.

PMID- 22657144
TI  - Isolation and identification of mycobacteria from captive reptiles.
AB  - The occurrence of Mycobacterium species in clinically healthy pet reptiles was
      studied in Italy during the period 2004-2006. The feces samples of 223 animals
      were examined bacteriologically. Thirty-seven strains were isolated, in
      particular from 13/18 (72.2%) ophidians, 13/134 (9.7%) saurians and 11/71 (15.5%)
      chelonians. The isolates were classified, after HPLC analysis of bromophenacyl
      esters of cell wall mycolic acids, as Mycobacterium fortuitum (14 strains,
      37.8%), Mycobacterium fortuitum-like (17, 45.9%), Mycobacterium peregrinum (4,
      10.8%), and Mycobacterium chelonae (1, 2.7%). M. fortuitum was isolated from
      seven pythons, five saurians and two turtles; M. fortuitum-like from six
      saurians, six pythons and five turtles; M. peregrinum from four turtles; M.
      chelonae from one lizard. One isolate from an Iguana iguana could not be
      identified by HPLC analysis showing a previously unreported profile. Comparative
      16S rDNA sequencing showed a low similarity with Mycobacterium triviale (97.2%)
      and Mycobacterium confluentis (97.1%). On the basis of such data the unidentified
      bacterium turned out to belong to a not yet described Mycobacterium species.

PMID- 22657145
TI  - Functionalizing gold nanoparticles with bluetongue virus multiple peptide
      antigens utilizing gold-thiol interaction: a novel approach to develop pen side
      test.
AB  - Bluetongue is an economically important viral disease of small ruminants. The
      present/current diagnostic kits and methods to diagnose BTV are laborious, time
      consuming and expensive. In the present study, we have attempted to develop a
      novel approach to detect BTV antibodies in sera that in future can be harnessed
      for developing a pen side diagnostic test. Briefly, we identified the
      immunodominant regions of the VP7 protein of BTV and synthesized them in the
      multiple antigenic peptide (MAP) format with cysteine at C-terminal of the lysine
      mosaic, which elicited highly ordered conformation as well as ELISA reactivity.
      Finally, we coated the MAP peptides on the gold nanoparticles that can be used to
      detect BTV specific antibodies in the sera using a spot test.

PMID- 22657146
TI  - Factors associated with work-family conflict stress among African American women.
AB  - Job demands and workplace culture variables associated with work-family conflict
      stress, in addition to workplace racial bias, were examined for a national sample
      of 607 African American women in 16 Fortune 1000 companies. Similar to other
      studies, women in this sample who had dependents were younger, had supervisory
      responsibilities, and experienced a less positive workplace culture, and those in
      professional job positions with high job demand were most likely to experience
      work-family stress. Married women who experienced a more subtle form of workplace
      racial bias reported more work-family conflict stress. Implications for social
      work policy, practice, and research are considered.

PMID- 22657147
TI  - Health situation of migrants with precarious status: review of the literature and
      implications for the Canadian context--Part A.
AB  - Migrants with precarious status (MPS) are an understudied population. Yet there
      are indications that they could be particularly vulnerable and confronted to
      health inequalities. This review of Canadian and international literature
      highlights that MPS, like other migrants, are confronted with deleterious living
      conditions and multiple obstacles to access healthcare. However, their status
      brings additional challenges and harmful health determinants. The situation of
      MPS may well be similar in Canada, where they could be numerous. Therefore it is
      crucial to better document this issue within the Canadian context. Part B of this
      article, reported elsewhere, further explores this topic.

PMID- 22657148
TI  - Examining HIV-positive parents' disclosure to their children: a biopsychosocial
      approach.
AB  - In the post HAART era, the biopsychosocial issues now facing HIV-positive parents
      concerning disclosure of their status to their children need to be understood in
      the context of chronic disease. This article describes the experiences of 101
      adult HIV-positive urban in-treatment mothers and fathers of school-age children
      on disclosure, psychological distress, social support, and symptom severity. Key
      variables associated with parents' HIV disclosure were the age of parent and of
      children in the household, parents' HIV-related symptoms, and parent ethnicity.
      Cultural and maturational, rather than psychological or social factors were
      significantly related to parents' HIV disclosure.

PMID- 22657149
TI  - HIV/AIDS program in Jharkhand: a critical review.
AB  - This article is an attempt to present and elaborate the HIV/AIDS scenario in
      Jharkhand state of India, services available, key issues, challenges, and
      concerns at various levels to mitigate the epidemic. It also examines the role of
      different stakeholders and agencies in halting and reversing the epidemic. The
      findings show that there are various challenges that need immediate attention.
      The article critically examines these issues in detail and suggests the approach
      to address the epidemic.

PMID- 22657150
TI  - Veterans use of non-VHA services: implications for policy and planning.
AB  - Most Veterans elect not to use the Veterans Health Administration (VHA), even if
      eligible, or access the VHA system but rely on non-VHA providers as well. Given
      considerable cross-system use, failure to account for non-VHA care can bias
      conclusions about prevalence and incidence in utilization, diagnoses, and other
      characteristics. Furthermore, though dual VHA and non-VHA use provides Veterans
      with additional service options, it makes it difficult for VHA to ensure
      continuity of care. To better coordinate services, the VHA needs to construct the
      necessary health information bridges while widening the purview of case
      management programs. These changes are especially important in light of increased
      demand for care among younger Veterans returning from Iraq and Afghanstain and
      older Veterans who served in previous wars.

PMID- 22657151
TI  - Beyond the perception and the obvious: what sex offender registries really tell
      us and why.
AB  - This work examines the sex offender registries in 49 states in terms of the
      public information they offer from a social construction and social reality
      standpoint. Social construction is the dominant perspective for the information
      given about sex offenders to the point where the market for public information
      may be failing in this regard. This failure could indeed be caused by how
      difficult it is for a society to look at such acts, focusing on the offender
      instead. Oregon and West Virginia emerge as registries higher on social
      construction and reality than others, though none emerges as clearly the most
      "informative." Third-party dissemination of information is explored.

PMID- 22657152
TI  - On the catalytic mechanism of human ATP citrate lyase.
AB  - ATP citrate lyase (ACL) catalyzes an ATP-dependent biosynthetic reaction which
      produces acetyl-coenzyme A and oxaloacetate from citrate and coenzyme A (CoA).
      Studies were performed with recombinant human ACL to ascertain the nature of the
      catalytic phosphorylation that initiates the ACL reaction and the identity of the
      active site residues involved. Inactivation of ACL by treatment with
      diethylpyrocarbonate suggested the catalytic role of an active site histidine
      (i.e., His760), which was proposed to form a phosphohistidine species during
      catalysis. The pH-dependence of the pre-steady-state phosphorylation of ACL with
      [gamma-(33)P]-ATP revealed an ionizable group with a pK(a) value of ~7.5, which
      must be unprotonated for the catalytic phosphorylation of ACL to occur.
      Mutagenesis of His760 to an alanine results in inactivation of the biosynthetic
      reaction of ACL, in good agreement with the involvement of a catalytic histidine.
      The nature of the formation of the phospho-ACL was further investigated by
      positional isotope exchange using [gamma-(18)O(4)]-ATP. The beta,gamma-bridge to
      nonbridge positional isotope exchange rate of [gamma-(18)O(4)]-ATP achieved its
      maximal rate of 14 s(-1) in the absence of citrate and CoA. This rate decreased
      to 5 s(-1) when citrate was added, and was found to be 10 s(-1) when both citrate
      and CoA were present. The rapid positional isotope exchange rates indicated the
      presence of one or more catalytically relevant, highly reversible phosphorylated
      intermediates. Steady-state measurements in the absence of citrate and CoA showed
      that MgADP was produced by both wild type and H760A forms of ACL, with rates at
      three magnitudes lower than that of k(cat) for the full biosynthetic reaction.
      The ATPase activity of ACL, along with the small yet significant positional
      isotope exchange rate observed in H760A mutant ACL (~150 fold less than wild
      type), collectively suggested the presence of a second, albeit unproductive,
      phosphoryl transfer in ACL. Mathematical analysis and computational simulation
      suggested that the desorption of MgADP at a rate of ~7 s(-1) was the rate
      limiting step in the biosynthesis of AcCoA and oxaloacetate.

PMID- 22657154
TI  - Ionization of amphiphilic acidic block copolymers.
AB  - The ionization behavior of an amphiphilic diblock copolymer poly(n-butyl
      acrylate(50%)-stat-acrylic acid(50%))(100)-block-poly(acrylic acid)(100)
      (P(nBA(50%)-stat-AA(50%))(100)-b-PAA(100), DH50) and of its equivalent triblock
      copolymer P(nBA(50%)-stat-AA(50%))(100)-b-PAA(200)-b-P(nBA(50%)-stat
      AA(50%))(100) (TH50) were studied by potentiometric titration either in pure
      water or in 0.5 M NaCl. These polymers consist of a hydrophilic acidic block
      (PAA) connected to a hydrophobic block, P(nBA(50%)-stat-AA(50%))(100), whose
      hydrophobic character has been mitigated by copolymerization with hydrophilic
      units. We show that all AA units, even those in the hydrophobic block could be
      ionized. However, the AA units within the hydrophobic block were less acidic than
      those in the hydrophilic block, resulting in the preferential ionization of the
      latter block. The preferential ionization of PAA over that of P(nBA(50%)-stat
      AA(50%))(100) was stronger at higher ionic strength. Remarkably, the covalent
      bonds between the PAA and P(nBA(50%)-stat-AA(50%))(100) blocks in the diblock or
      the triblock did not affect the ionization of each block, although the self
      association of the block copolymers into spherical aggregates modified the
      environment of the PAA blocks compared to when PAA was molecularly dispersed.

PMID- 22657153
TI  - Protective role of methionine sulfoxide reductase A against ischemia/reperfusion
      injury in mouse kidney and its involvement in the regulation of trans-sulfuration
      pathway.
AB  - AIMS: Methionine sulfoxide reductase A (MsrA) and methionine metabolism are
      associated with oxidative stress, a principal cause of ischemia/reperfusion (I/R)
      injury. Herein, we investigated the protective role of MsrA against kidney I/R
      injury and the involvement of MsrA in methionine metabolism and the trans
      sulfuration pathway during I/R. RESULTS: We found that MsrA gene-deleted mice
      (MsrA(-/-)) were more susceptible to kidney I/R injury than wild-type mice
      (MsrA(+/+)). Deletion of MsrA enhanced renal functional and morphological
      impairments, congestion, inflammatory responses, and oxidative stress under I/R
      conditions. Concentrations of homocysteine and H(2)S in the plasma of control
      MsrA(-/-) mice were significantly lower than those in control MsrA(+/+) mice. I/R
      reduced the levels of homocysteine and H(2)S in both MsrA(+/+) and MsrA(-/-)
      mice, and these reductions were significantly more profound in MsrA(-/-) than in
      MsrA(+/+) mice. I/R reduced the expression and activities of cystathionine-beta
      synthase (CBS) and cystathionine-gamma-lyase (CSE), both of which are H(2)S
      producing enzymes, in the kidneys. These reductions were more profound in the
      MsrA(-/-) mice than in the MsrA(+/+)mice. INNOVATION: The data provided herein
      constitute the first in vivo evidence for the involvement of MsrA in regulating
      methionine metabolism and the trans-sulfuration pathway under normal and I/R
      conditions. CONCLUSION: Our data demonstrate that MsrA protects the kidney
      against I/R injury, and that this protection is associated with reduced oxidative
      stress and inflammatory responses. The data indicate that MsrA regulates H(2)S
      production during I/R by modulating the expression and activity of the CBS and
      CSE enzymes.

PMID- 22657155
TI  - Cauterization of the germinal nail matrix using phenol applications of differing
      durations: a histologic study.
AB  - BACKGROUND: Phenol has been used for more than 60 years in the treatment of
      ingrown toenails. Many reports have documented the safety and effectiveness of
      phenol matricectomy, although with variable treatment application times.
      OBJECTIVE: We performed research to determine the application time required for
      phenol matricectomy for complete denaturation of the nail matrix to occur at a
      concentration of 88%. Identifying the optimal time required to destroy the
      germinal matrix without causing further soft-tissue damage should reduce the
      potential for complications. METHODS: Thirty anatomic cadaveric fresh hallux
      samples were used to perform phenol matricectomy. The applications were for 1 to
      6 minutes using 10 samples per time point and analyzed by hematoxylin-eosin
      staining to determine the presence or absence of the basal or germinal layer of
      the nail bed epithelium (NBE). RESULTS: After a 1-minute application of 88%
      phenol solution, only superficial damage to the NBE was noted, with the basal
      layer primarily intact. After a 2-minute application, the nail plate was avulsed
      with a thin basal layer remaining. After a 3-minute application, full-thickness
      necrosis of the NBE was noted in 6 of the 10 specimens. After 4-, 5-, and 6
      minute applications, full-thickness necrosis of the NBE was noted and the basal
      layer was completely destroyed in all 30 specimens. LIMITATIONS: The study was
      performed in cadaveric fresh specimens. CONCLUSIONS: Application of 88% phenol
      solution for at least 4 minutes is necessary for complete destruction of the nail
      matrix, creating an environment that avoids nail regrowth.

PMID- 22657156
TI  - Three-dimensional histology for dermatofibrosarcoma protuberans: case series and
      surgical technique.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant skin
      tumor that may also infiltrate dermis and subcutaneous tissue. Although the
      mainstay of treatment has been wide local excision, during the last decade three
      dimensional (3D) histology surgery has proven very effective for the treatment of
      this tumor. OBJECTIVE: We sought to evaluate the effectiveness of 3D histology
      surgery for the treatment of DFSP. METHODS: We retrospectively reviewed charts of
      patients with DFSP treated in our unit with 3D histology surgery between April
      2000 and May 2011. Age at onset, gender, duration of tumor, previous treatment,
      lesion site, number of surgical stages, postsurgical defect size, closure
      technique, and follow-up were registered. RESULTS: A total of 29 patients were
      included. Mean patient age was 40.7 years. Fifteen lesions were located on the
      trunk, 11 on the extremities, and 3 in the head and neck region. Twelve patients
      had primary tumors and 17 were referred to us after incomplete excision. The
      average number of 3D histology surgical stages required for tumor clearance was
      1.4. Mean postsurgical defect size was 26 cm(2). All lateral and deep borders
      excised were tumor-free. Mean follow-up period was 68 months (range 12-142
      months) with a 0% recurrence rate. LIMITATIONS: This was a retrospective review.
      CONCLUSION: Three-dimensional histology surgery with paraffin sections is
      effective for the treatment of DFSP and feasible in an outpatient setting. The
      low recurrence rates obtained confirm the oncologic efficacy of the procedure.
      Furthermore, designing closure on the basis of focally affected margins improves
      functional and aesthetic outcomes without compromising oncological effectiveness.

PMID- 22657157
TI  - A long-term follow-up study of methotrexate in juvenile localized scleroderma
      (morphea).
AB  - BACKGROUND: Recent studies report that methotrexate (MTX) is beneficial in the
      treatment of juvenile localized scleroderma (JLS) but little is known about its
      long-term effectiveness. OBJECTIVE: We assessed the therapeutic role of MTX in
      children with JLS who were followed up for a prolonged period. METHODS: A cohort
      of patients with JLS, previously enrolled in a double-blind, randomized
      controlled trial and treated with oral MTX (15 mg/m(2)/wk) and prednisone (1
      mg/kg/d, maximum 50 mg) for the first 3 months, were prospectively followed up.
      Lesions were evaluated clinically, with infrared thermography, and by a
      computerized skin score. Response to treatment was defined as: (1) no new
      lesions; (2) skin score rate less than 1; and (3) decrease in lesion temperature
      by at least 10% compared with baseline. Clinical remission (CR) on medication was
      defined when response was maintained, on treatment, for at least 6 months, and
      complete CR when response was maintained, without treatment, for at least 6
      months. RESULTS: Of 65 patients treated with MTX, 48 (73.8%) were responders, 10
      (15.4%) relapsed by 24 months since MTX start, and 7 (10.8%) were lost to follow
      up. Among the responders, 35 (72.9%) maintained CR for a mean of 25 months and 13
      (27.1%) were in CR on medication. Adverse effects seen in 28 patients (48.3%)
      were generally mild and never required treatment discontinuation. LIMITATIONS:
      The use of objective measures not widely available, such as infrared thermography
      and computerized skin score, makes it difficult to compare data from previous
      studies. CONCLUSIONS: Long-term MTX therapy is beneficial and well tolerated for
      JLS.

PMID- 22657158
TI  - Postharvest application of methyl jasmonate for improving quality retention of
      Agaricus bisporus fruit bodies.
AB  - The influence of methyl jasmonate (MeJA) on postharvest quality and enzyme
      activities, gene expression level, and the functional component content linked to
      postharvest deterioration in Agaricus bisporus (J.E. Lange) Imbach fruit bodies
      was investigated. Freshly harvested fruit bodies were treated with 0 (control),
      10 and 100 MUM MeJA vapor at 20  degrees C for 12 h and then stored at 10 
      degrees C for up to 7 days. The results indicated that treatments with 100 MUM
      MeJA vapor maintained a high level of soluble protein and total sugar, delayed
      browning, promoted the accumulation of phenolics and flavonoids, and inhibited
      the increase of respiratory rate and membrane leakage. Furthermore, 100 MUM MeJA
      inhibited the activities of polyphenoloxidase, increased the antioxidant enzymes
      activities of catalase and superoxide dismutase, and lowered relative expression
      levels of three genes encoding polyphenol oxidase (AbPPO1, AbPPO2, and AbPPO3)
      throughout the storage period. Comparatively, 10 MUM MeJA also had a clear
      beneficial effect on postharvest mushroom quality maintenance but was not as
      effective as 100 MUM MeJA treatment. These findings suggest that application of
      MeJA could have potential in maintaining the quality of harvested A. bisporus
      fruit bodies. 

PMID- 22657159
TI  - Sexuality and occupational therapy in Ireland--a case of ambivalence?
AB  - PURPOSE: To examine occupational therapists' attitudes and beliefs towards
      addressing clients' sexuality and sexual needs during everyday practice. METHOD:
      A cross-sectional internet based survey was conducted among a convenience sample
      (n = 120) of occupational therapists working in Ireland. Respondents' perceived
      knowledge, awareness and confidence to address sexuality were examined.
      Respondents also reported current practice relating to addressing sexuality.
      RESULTS: Sexuality although considered a legitimate area of practice was rarely
      addressed by occupational therapists. Participants reported low levels of
      awareness, knowledge and confidence relating to addressing client sexuality.
      Specific barriers identified by participants to addressing sexuality include lack
      of training, perceived lack of readiness of the client, client's age and marital
      status, perceived appropriateness of sexuality for the client. CONCLUSION:
      Occupational therapists in Ireland appear to be ambivalent towards the inclusion
      of sexuality as part of practice. Current practice rarely includes clients'
      sexual needs and appears to be influenced by a hetro-normative conservative
      discourse of sexuality. Additional training and education, which challenges
      current assumptions relating to sexuality, is required to ensure that the needs
      of people with illness and disability are met.

PMID- 22657160
TI  - Statistics of spike trains in conductance-based neural networks: Rigorous
      results.
AB  - We consider a conductance-based neural network inspired by the generalized
      Integrate and Fire model introduced by Rudolph and Destexhe in 1996. We show the
      existence and uniqueness of a unique Gibbs distribution characterizing spike
      train statistics. The corresponding Gibbs potential is explicitly computed. These
      results hold in the presence of a time-dependent stimulus and apply therefore to
      non-stationary dynamics.

PMID- 22657161
TI  - Concurrent psychiatric disorders are associated with significantly poorer quality
      of life in patients with rheumatoid arthritis.
AB  - OBJECTIVES: To study the effect of concurrent psychiatric disorders on health
      related quality of life (HRQOL) in patients with rheumatoid arthritis (RA).
      METHODS: Consecutive Chinese patients who fulfilled the American College of
      Rheumatology (ACR) criteria for RA were recruited and interviewed by a
      psychiatrist for psychiatric disorders using the Chinese Bilingual Structured
      Clinical Interview for DSM-IV Axis I Disorders, Patient version (CB-SCID-I/P).
      HRQOL was assessed by the validated Chinese version of the 36-item Short Form
      Health Survey (SF-36). Sociodemographic and clinical data were also collected.
      Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy -
      Fatigue scale (FACIT-F). RESULTS: Two hundred patients with RA were studied (79%
      women, mean age 51.4 +/- 10.5 years; median RA duration 4.0 years). Forty-seven
      (23.5%) patients were diagnosed with a psychiatric disorder: depressive disorders
      in 29 patients and anxiety disorders in 26 patients. Patients with either
      condition had significantly higher fatigue scores (26 +/- 8.8 vs. 16 +/- 6.9, p <
      0.001) and were more likely to be unemployed (p = 0.02) and dependent on
      government subsidy for living (p < 0.001) than those without. The scores of the
      eight domains and the physical and mental components of the SF-36 were
      significantly lower in RA patients with psychiatric disorders (p < 0.001 in all).
      In a linear regression model, the presence of either depressive or anxiety
      disorders (beta = -0.23, p < 0.001), older age (beta = -0.16, p = 0.006), self
      perceived pain (beta = -0.25, p < 0.001) and fatigue (beta = -0.42, p < 0.001)
      were independently and inversely associated with the total SF-36 score after
      adjustment for disease activity and other sociodemographic variables.
      CONCLUSIONS: Concomitant depressive or anxiety disorders in RA patients are
      associated with significantly poorer HRQOL. Early identification and treatment of
      psychiatric disorders in RA patients are warranted.

PMID- 22657245
TI  - Nanoemulsion stability: experimental evaluation of the flocculation rate from
      turbidity measurements.
AB  - The coalescence of liquid drops induces a higher level of complexity compared to
      the classical studies about the aggregation of solid spheres. Yet, it is commonly
      believed that most findings on solid dispersions are directly applicable to
      liquid mixtures. Here, the state of the art in the evaluation of the flocculation
      rate of these two systems is reviewed. Special emphasis is made on the
      differences between suspensions and emulsions. In the case of suspensions, the
      stability ratio is commonly evaluated from the initial slope of the absorbance as
      a function of time under diffusive and reactive conditions. Puertas and de las
      Nieves (1997) developed a theoretical approach that allows the determination of
      the flocculation rate from the variation of the turbidity of a sample as a
      function of time. Here, suitable modifications of the experimental procedure and
      the referred theoretical approach are implemented in order to calculate the
      values of the stability ratio and the flocculation rate corresponding to a
      dodecane-in-water nanoemulsion stabilized with sodium dodecyl sulfate. Four
      analytical expressions of the turbidity are tested, basically differing in the
      optical cross section of the aggregates formed. The first two models consider the
      processes of: a) aggregation (as described by Smoluchowski) and b) the
      instantaneous coalescence upon flocculation. The other two models account for the
      simultaneous occurrence of flocculation and coalescence. The latter reproduce the
      temporal variation of the turbidity in all cases studied (380<=[NaCl]<=600 mM),
      providing a method of appraisal of the flocculation rate in nanoemulsions.

PMID- 22657247
TI  - Fibroids and pregnancy outcomes.

PMID- 22657248
TI  - Endometrial reconstruction from stem cells.
AB  - Adult stem cells have been identified in the highly regenerative human
      endometrium on the basis of their functional attributes. They can reconstruct
      endometrial tissue in vivo suggesting their possible use in treating disorders
      associated with inadequate endometrium. The identification of specific markers
      for endometrial mesenchymal stem cells and candidate markers for epithelial
      progenitor cells enables the potential use of endometrial stem/progenitor cells
      in reconstructing endometrial tissue in Asherman syndrome and intrauterine
      adhesions.

PMID- 22657250
TI  - A new mobile ubiquitous computing application to control obesity: SapoFit.
AB  - The objective of this work was the proposal, design, construction and validation
      of a mobile health system for dietetic monitoring and assessment, called SapoFit.
      This application may be personalized to keep a daily personal health record of an
      individual's food intake and daily exercise and to share this with a social
      network. The initiative is a partnership with SAPO - Portugal Telecom. SapoFit
      uses Web services architecture, a relatively new model for distributed computing
      and application integration. SapoFit runs on a range of mobile platforms, and it
      has been implemented successfully in a range of mobile devices and has been
      evaluated by over 100 users. Most users strongly agree that SapoFit has an
      attractive design, the environment is user-friendly and intuitive, and the
      navigation options are clear.

PMID- 22657249
TI  - Developing symptom-based predictive models of endometriosis as a clinical
      screening tool: results from a multicenter study.
AB  - OBJECTIVE: To generate and validate symptom-based models to predict endometriosis
      among symptomatic women prior to undergoing their first laparoscopy. DESIGN:
      Prospective, observational, two-phase study, in which women completed a 25-item
      questionnaire prior to surgery. SETTING: Nineteen hospitals in 13 countries.
      PATIENT(S): Symptomatic women (n = 1,396) scheduled for laparoscopy without a
      previous surgical diagnosis of endometriosis. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Sensitivity and specificity of endometriosis diagnosis predicted by
      symptoms and patient characteristics from optimal models developed using multiple
      logistic regression analyses in one data set (phase I), and independently
      validated in a second data set (phase II) by receiver operating characteristic
      (ROC) curve analysis. RESULT(S): Three hundred sixty (46.7%) women in phase I and
      364 (58.2%) in phase II were diagnosed with endometriosis at laparoscopy.
      Menstrual dyschezia (pain on opening bowels) and a history of benign ovarian
      cysts most strongly predicted both any and stage III and IV endometriosis in both
      phases. Prediction of any-stage endometriosis, although improved by ultrasound
      scan evidence of cyst/nodules, was relatively poor (area under the curve [AUC] =
      68.3). Stage III and IV disease was predicted with good accuracy (AUC = 84.9,
      sensitivity of 82.3% and specificity 75.8% at an optimal cut-off of 0.24).
      CONCLUSION(S): Our symptom-based models predict any-stage endometriosis
      relatively poorly and stage III and IV disease with good accuracy. Predictive
      tools based on such models could help to prioritize women for surgical
      investigation in clinical practice and thus contribute to reducing time to
      diagnosis. We invite other researchers to validate the key models in additional
      populations.

PMID- 22657252
TI  - Assessment of pharmacodynamic equivalence and tolerability of lanthanum carbonate
      oral powder and tablet formulations: a single-center, randomized, open-label, 2
      period crossover study in healthy subjects.
AB  - BACKGROUND: Phosphate binders are commonly used in tablet form to help patients
      with hyperphosphatemia limit their absorption of dietary phosphate. These
      patients frequently have a heavy tablet burden so alternative formulations
      provide choice and may support adherence. Lanthanum carbonate (LC) is a phosphate
      binder currently available as a chewable tablet. This study was conducted to
      support an application for marketing authorization for the oral powder
      formulation within the European Union. OBJECTIVE: The goal of this study was to
      examine the pharmacodynamics, pharmacokinetics, and tolerability of an oral
      powder formulation of LC compared with the reference chewable tablet formulation.
      METHODS: A Phase I, single-center, randomized, open-label, 2-period, crossover
      study to assess pharmacodynamic equivalence of the 2 formulations was conducted
      in healthy adults aged 18 to 55 years receiving a diet standardized for phosphate
      content. Individuals were randomized to receive a different formulation in each
      period, taking 10 doses of 1000-mg LC at 3000 mg/d per period with an intervening
      washout of >=14 days. The primary pharmacodynamic variable was mean daily
      excretion of urinary phosphorus over 3 days while receiving LC. Pharmacodynamic
      equivalence was confirmed if the 90% CI for the difference between formulations
      in least squares (LS) mean excreted urinary phosphorus was within +/-20% of the
      LS mean value for the tablet formulation. Secondary end points included
      determination of pharmacokinetic parameters and assessment of tolerability by
      recording of adverse events. RESULTS: In total, 72 individuals entered the study.
      They were predominantly men (72.2%), with a mean (SD) age of 31.4 (8.26) years
      and a BMI of 25.8 (2.45) kg/m(2). The LS mean (SE) excreted urinary phosphorus
      was 16.8 (0.48) mmol/d during administration of LC tablets (+/-20% = +/-3.35
      mmol/d). The corresponding value during administration of LC oral powder was 15.2
      (0.48) mmol/d; 90% CI for the difference between formulations was -2.38 to -0.82
      mmol/d, confirming pharmacodynamic equivalence. The most common adverse events
      were gastrointestinal, and no serious adverse events were recorded. CONCLUSIONS:
      In this multiple-dose study, the oral powder and tablet formulations of LC were
      well tolerated and met the regulatory criteria for pharmacodynamic equivalence in
      these healthy volunteers. ClinicalTrials.gov identifier: NCT00880750.

PMID- 22657251
TI  - Akt (protein kinase B) isoform phosphorylation and signaling downstream of mTOR
      (mammalian target of rapamycin) in denervated atrophic and hypertrophic mouse
      skeletal muscle.
AB  - BACKGROUND: The present study examines the hypothesis that Akt (protein kinase
      B)/mTOR (mammalian target of rapamycin) signaling is increased in hypertrophic
      and decreased in atrophic denervated muscle. Protein expression and
      phosphorylation of Akt1, Akt2, glycogen synthase kinase-3beta (GSK-3beta),
      eukaryotic initiation factor 4E binding protein 1 (4EBP1), 70 kD ribosomal
      protein S6 kinase (p70S6K1) and ribosomal protein S6 (rpS6) were examined in six
      days denervated mouse anterior tibial (atrophic) and hemidiaphragm (hypertrophic)
      muscles. RESULTS: In denervated hypertrophic muscle expression of total Akt1,
      Akt2, GSK-3beta, p70S6K1 and rpS6 proteins increased 2-10 fold whereas total
      4EBP1 protein remained unaltered. In denervated atrophic muscle Akt1 and Akt2
      total protein increased 2-16 fold. A small increase in expression of total rpS6
      protein was also observed with no apparent changes in levels of total GSK-3beta,
      4EBP1 or p70S6K1 proteins. The level of phosphorylated proteins increased 3-13
      fold for all the proteins in hypertrophic denervated muscle. No significant
      changes in phosphorylated Akt1 or GSK-3beta were detected in atrophic denervated
      muscle. The phosphorylation levels of Akt2, 4EBP1, p70S6K1 and rpS6 were
      increased 2-18 fold in atrophic denervated muscle. CONCLUSIONS: The results are
      consistent with increased Akt/mTOR signaling in hypertrophic skeletal muscle.
      Decreased levels of phosphorylated Akt (S473/S474) were not observed in
      denervated atrophic muscle and results downstream of mTOR indicate increased
      protein synthesis in denervated atrophic anterior tibial muscle as well as in
      denervated hypertrophic hemidiaphragm muscle. Increased protein degradation,
      rather than decreased protein synthesis, is likely to be responsible for the loss
      of muscle mass in denervated atrophic muscles.

PMID- 22657253
TI  - System-wide implementation of the use of an extended-infusion
      piperacillin/tazobactam dosing strategy: feasibility of utilization from a
      children's hospital perspective.
AB  - BACKGROUND: Use of extended infusions of piperacillin/tazobactam (PT) in adult
      patients has been described, but data in children are limited. OBJECTIVE: The
      goal of this study was to determine the feasibility of using an extended-infusion
      PT dosing strategy as the standard of care in a children's hospital. METHODS:
      This was a prospective observational study of patients aged >30 days who received
      PT after admission to a freestanding, tertiary care children's hospital. After
      institution of an extended-infusion PT dosing protocol as the standard dosing
      option, patients receiving PT were prospectively assessed for presence of and
      reasons for changes in dosing regimen. RESULTS: A total of 332 patients, with a
      median age of 5 years (interquartile range, 1.9-12 years) and median weight of
      19.9 kg (interquartile range, 11.7 - 37.6 kg) received PT (100 mg/kg based on
      piperacillin component). Extended-infusion PT was used for the duration of PT
      therapy in 92% (n = 304) of patients. Twenty-eight patients (8%) received a
      traditional infusion over 30 minutes, with 19 of 28 being changed from extended
      infusion and 9 of 28 being empirically prescribed traditional infusion PT. The
      most commonly encountered reason for not using extended infusions was
      coadministration of vancomycin (17 of 28 [61%]) and lack of compatibility data
      with PT. Dosing errors, which were voluntarily reported, were infrequent (1.8% [n
      = 6]). The few observed dosing errors were likely attributable to the overall
      ordering process at our institution, which requires ordering as the milligram per
      kilogram dose as total PT rather than based on piperacillin component as is
      commonly documented in pediatric dosing references. CONCLUSIONS: Results of this
      study suggest that extended-infusion PT dosing was feasible in this specific
      children's hospital. Ninety-two percent of patients received our institution's
      preferred dosing regimen; a small percentage of patients still needed to receive
      traditional infusion times.

PMID- 22657254
TI  - Clinical and cost effectiveness of bevacizumab + FOLFIRI combination versus
      FOLFIRI alone as first-line treatment of metastatic colorectal cancer in South
      Korea.
AB  - BACKGROUND: Bevacizumab has been extensively investigated in combination with
      various standard chemotherapies in the treatment of metastatic colorectal cancer
      (mCRC). However, a comparison to irinotecan + infusional 5
      fluorouracil/leucovorin (FOLFIRI) is lacking. OBJECTIVE: To explore clinical
      effectiveness and cost-effectiveness of adding bevacizumab to a regimen of
      FOLFIRI for the first-line treatment of mCRC in the Republic of Korea by
      conducting an indirect treatment comparison. METHODS: A health-economic model was
      developed to investigate the possible health outcomes (life-years gained [LYG]),
      direct costs, and incremental cost-effectiveness ratio (ICER) of adding
      bevacizumab to a FOLFIRI regimen. Data on progression-free and overall survival
      were derived from randomized clinical trials and were used in the indirect
      treatment comparison. The annual discount rate for costs and outcomes was 5%. A
      lifetime horizon of 8 years was used. Sensitivity analyses were carried out on
      all pivotal model assumptions. RESULTS: Incremental mean overall survival among
      patients treated with bevacizumab + FOLFIRI varied between 8.6 and 15.7 months
      compared with patients treated with FOLFIRI alone. The deterministic base-case
      result was 1.177 LYG. The discounted ICERs ranged from MU31.8 to MU39.5
      million/LYG, with the base-case result being MU34.5 million/LYG. Treatment effect
      had the most impact on the outcomes in this model. CONCLUSIONS: Although there is
      no formal threshold for ICER per LYG in Korea, funding may be considered for
      bevacizumab + FOLFIRI, particularly if the severity and end-of-life nature of
      mCRC is taken into account.

PMID- 22657255
TI  - Evaluation of posture signal using entropy analysis and fractal dimension in
      adults with Down syndrome.
AB  - The aim of this study was to explore new techniques in analysing postural control
      using nonlinear time-series analysis and to relate these results with the
      clinical knowledge on the postural system in Down syndrome (DS) subjects. In
      order to achieve the goal, we analysed the time domain and the frequency domain
      behaviour, the fractal dimension and the entropy of the centre of pressure signal
      in both directions during quiet standing in 35 participants with DS, comparing
      the results with a control population. DS patients evidenced a lack in postural
      control in anterior-posterior direction due to the impairment both in the high
      organisation and synergies and in the impairments due to ligament laxity and
      hypotonia. Maintaining posture is a task achieved by the integration of visual,
      vestibular and somatosensory receptors and the dynamical nature of this signal
      gives fundamental data about the lack of postural control in specific
      pathological condition. 

PMID- 22657256
TI  - [Guidelines for the management of tuberous sclerosis complex renal disease].
AB  - PURPOSE: To review existing literature and deduce guidelines for the management
      of renal disease in patients with tuberous sclerosis complex (TSC). PATIENTS:
      After review of literature, a core panel of five physicians wrote a draft that
      was evaluated by 14 reviewers who used a 9-level scale (1: total disagreement; 9:
      total agreement). The guidelines were then reformulated until each item received
      a median score superior or equal to 8. RESULTS: Forty-eight to 80 % of TSC
      patients have significant renal involvement including angiomyolipomas (AMLs),
      cysts, malignant tumors and renal insufficiency. It is recommended to perform an
      abdominal ultrasound (and serum creatinine if abnormal ultrasound) when TSC is
      diagnosed. This work-up will be repeated every 3-5years if normal. Associated
      autosomal dominant polycystic kidney disease must be suspected in case of
      numerous and large cysts. After the age of 20, follow-up should use computed
      tomography (CT) or MRI that are more precise than ultrasound for the measurement
      of AMLs. Biopsy of a renal mass should be discussed in case of calcifications,
      necrosis or rapid growth. Females with TSC should undergo screening for pulmonary
      lymphangioleiomyomatosis by CT at the age of 18, and, if negative at the age of
      30-40. Acute bleeding should be treated with percutaneous embolization.
      Asymptomatic angiomyolipomas with several risk factors (size>80mm, predominant
      vascular component, micro-aneurysms) should undergo prophylactic treatment, if
      possible using embolization. The role of mTOR inhibitors in the management of
      angiomyolipomas needs to be defined. CONCLUSION: Standardization of follow-up and
      treatment is necessary to improve the management of TSC renal involvement.

PMID- 22657257
TI  - [Benefit of bladder and upper urinary tract urothelial tumors lymph node
      dissection: review from the Bladder Cancer Committee of the French National
      Association of Urology ("CC-AFU Vessie")].
AB  - INTRODUCTION: Lymph node dissection during radical cystectomy or
      nephroureterectomy confers improved prognosis and eventually therapeutic
      advantage. The aim of this update is to clarify the anatomical limits of the
      lymph node dissection, imaging related techniques, possible difficulties related
      to pathological analysis, its prognostic value and adjuvant treatments. METHOD: A
      literature review was performed using PubMed database with a combination of the
      following keywords: "urothelial carcinoma", "lymph node excision", "imaging",
      "pathology analysis", "prognosis", "chemotherapy" and "radiotherapy". RESULTS:
      Regarding bladder tumours, extended lymph node dissection is usually performed up
      to the division of the iliac vessels and the crossing of the ureters. The CT scan
      is the recommended imaging technique for lymph node staging but its sensitivity
      is low. Pathological examination should include perivesicle lymph nodes analysis
      and report the number of normal and metastatic lymph nodes separately. The
      prognosis is correlated to the total number of lymph nodes removed and to the
      extent of the excision. The lymph node density (number of metastatic nodes/normal
      nodes) is the most important prognosis factor. Adjuvant chemotherapy has not
      demonstrated a clear advantage. Its most efficient modality is a combination
      including cisplatin. For upper urinary tract tumours, lymph node dissection may
      have an impact on survival but definitive conclusion is limited by the lack of
      surgical technique and indications standardisation. CONCLUSION: Extended lymph
      node dissection improves survival of bladder cancer and prognosis assessment that
      could eventually be used to stratify patient requiring adjuvant treatment (level
      of evidence 3). Improvement on survival was also suggested for upper urinary
      tract tumors (level of evidence 4).

PMID- 22657258
TI  - [Partial versus radical nephrectomy for renal cell carcinoma involving peri renal
      fat. Oncological and functional outcomes].
AB  - PURPOSE: In the latest guidelines of the European Association of Urology, partial
      nephrectomy was a reference standard in tumors less than 7cm confined to the
      kidney. The invasion of the perirenal fat and therefore dissection in a
      potentially tumor tissue with an increased risk of recurrence. MATERIAL: From
      1995 to 2009, we retrospectively evaluated the oncological outcomes of partial
      versus radical nephrectomy in tumors with local extension beyond the boundaries
      of the kidney, without adrenal involvement or metastatic lymph node extension. We
      evaluated the histological factors influencing the prognostic. RESULTS: A total
      of 43patients have been included (ten partial and 33radical nephrectomy). We did
      not found any significant difference in terms of specific and recurrence-free
      survival between partial and radical nephrectomy in tumor invading the perirenal
      fat (P=0.739 and P=0.683 respectively). Factors influencing the prognosis were
      the Fuhrman grade (P=0.010), the invasion of the urinary tract (P=0.017) and the
      presence of a positive surgical margin (P=0.041). The renal function was better
      after partial nephrectomy. The complication rate was similar between partial and
      radical nephrectomy. CONCLUSION: The perirenal fat invasion by kidney tumor did
      not impact the oncological outcomes of partial versus radical nephrectomy with
      better functional outcomes for partial nephrectomy.

PMID- 22657259
TI  - [Characteristics of acute pyelonephritis in renal transplant patients].
AB  - INTRODUCTION: Renal transplantation is an attractive alternative to haemodialysis
      for patients with renal failure. Preserving renal function after renal
      transplantation depends on rejection episodes and infections of the graft.
      PURPOSE: To clarify the characteristics of acute pyelonephritis encountered in a
      population of kidney transplant patients and to discern risk factors occurring
      during the first year after transplantation. METHOD: Data for all renal
      transplantations between January 1, 2006, and December 31, 2007 came from a
      database. Patients were at least 18 years old. A retrospective analysis was done.
      RESULTS: One hundred and eighty-four patients were included in the study. The
      incidence of acute pyelonephritis was 10.9%. In our sample, there were
      significantly more women who experienced pyelonephritis (P=0.012). Patients who
      had grafts with at least one episode of acute pyelonephritis were significantly
      younger (P=0.013) than transplanted patients without a history of acute
      pyelonephritis (44.4+/-10.5 and 52.2+/-13.4 years, respectively). CONCLUSION: Our
      study shows a lower incidence of pyelonephritis compared with the literature.
      Moreover, we found that young age and female gender were risk factors for
      developing this infection.

PMID- 22657260
TI  - [Pancreas transplantation and venous thrombosis: multivariate analysis of risk
      factors].
AB  - OBJECTIVE: Portal veinous thrombosis (VT) in the pancreatic transplant (6 to 20%
      of the cases) is the first cause of early loss of the transplant. Our objective
      was to identify the risk factors of VT in our experiment. METHOD: The sample
      group includes 106 patients who underwent pancreas transplantation (portal venous
      drainage, enteric-drained pancreas) within our institute of transplantation from
      2004 until 2010. We completed a portal vein extension graft in 25% of the cases.
      First of all, risk factors were selected from preoperative and operative data
      with an univariate analysis. We then carried out a multivariate analysis of these
      factors (binary logistic regression). The threshold P was 0.05. RESULTS: Sixteen
      patients (15%) showed a VT. Eight of them developed a total thrombosis and
      required a transplantectomy. Three risk factors of VT were isolated by the
      multivariate analysis: a BMI of the receiver>25kg/m(2) (Odds Ratio [OR]=6.977), a
      portal vein extension graft (OR=4.1) and an age of the donor>45 years (OR=4.432).
      CONCLUSIONS: The knowledge of these risk factors of thrombosis allows the
      implementation of preventive measures (selection of the donor, nutritional
      support of the receiver in the registration if BMI>25kg/m(2)). The portal
      lengthening should be avoided by an attentive retrieval of the transplant
      (without shorter section of the portal vein). Nevertheless, the presence of one
      of these risk factors in a transplant patient should lead to start an
      antithrombotic treatment.

PMID- 22657261
TI  - [Accuracy of prostate biopsies to evaluate tumor location in prostate cancer].
AB  - INTRODUCTION: The therapeutic approach of prostate cancer depends mainly on
      pathological criteria obtained through prostate biopsy. The low accuracy of
      prostate biopsy for Gleason grade determination is well known but its accuracy
      for bilateral or multifocal tumor has not been evaluated. The goal of this study
      was to assess the concordance between prostate biopsy and whole prostate specimen
      obtained after radical prostatectomy especially for bilateral and/or multifocal
      tumor. METHODS: We retrospectively compared the pathological results of prostate
      biopsy cores to the prostate specimen in patients who underwent radical
      prostatectomy in our department between the 01/01/1999 and the 31/12/2008. The
      criteria analyzed were the Gleason score, tumor bilaterality or multifocality.
      The impact of the number of prostate biopsy cores was also analyzed. RESULTS: Two
      hundred and five complete histological records were studied. Regarding the
      Gleason score overall concordance was 55%. In 38%, prostate biopsies downgraded
      the Gleason score. This concordance decreased with tumor differentiation (90.6%
      for Gleason 6 vs. 31% for Gleason greater than 7). For the tumor bilaterality,
      78% of cancers affected both lobes at the definitive specimen analysis while only
      49% were bilateral at prostate biopsies, achieving a concordance of 61%.
      Multifocal disease was observed in 36% at definitive pathology analysis with low
      concordance with prostate biopsies (36%). The number of biopsies increased the
      concordance for the Gleason score (60 to 81% for Gleason 7 and from 28 to 50% for
      Gleason greater than 7) and tumor location (44 to 70%). CONCLUSION: Pathological
      criteria and tumor mapping obtained from prostate biopsies were not very reliable
      especially when the tumor was poorly differentiated. An increased number of
      prostate biopsy core improved the sensitivity and specificity for the Gleason
      score diagnostic and of the tumor mapping.

PMID- 22657262
TI  - [Continent cystostomy: monocentric experience].
AB  - AIMS: To evaluate the feasibility, the efficiency, the results of continent
      cystostomy in adult population. MATERIAL AND METHODS: Retrospective study of
      patients who underwent a continent cystostomy between 1987 and 2011. RESULTS:
      Forty-three patients underwent a continent cystostomy (13 men and 30 women). The
      mean age at surgery was 53.4+/-14.6years. The mean BMI was 25kg/m(2). No death in
      relation with the cystostomy was reported. Thirty-two patients had a neurological
      pathology (74.4%), 11 a pathology other than neurological (25.6%). A retention
      bladder was reported for 12 patients (27.9%), 17 (39.5%) were incontinent, and 14
      (32.6%) had a mixed symptomatology. All patients had urodynamics and an
      evaluation of the urinary tract. Nineteen appendicovesicostomy were made, 15
      double Monti-procedure, six simple Monti-procedure, three channels were made of
      an association of ileon and appendix. Seventeen patients underwent an
      augmentation cystoplasty in combination with the continent catheterizable
      conduit. The mean follow-up was 47.6+/-29months. Continence was achieved in 37
      patients (86%), two patients underwent a Bricker. Stomal stenosis occurred in
      eight patients (18.6%), with a median time of 16.1+/-20.4 months. Leakage
      occurred after bladder neck closure for two patients (4.6%). Clean intermittent
      catheterization were performed by 30 patients, catheterization by a care giver
      for four patients, seven did not use their stomy because of the evolution of
      their causal pathology, or because of an intercurrent pathology. No difference
      between the channels (Mitrofanoff versus Monti) was reported. CONCLUSION:
      Continent catherizable cystostomy were a feasible method of continent urinary
      diversion in an adult population. This study demonstrated their feasibility in an
      adult population and their long-term efficiency with a mean follow-up of
      47.6months and 127months for one of them. With a rate of continence upper than
      80%, it was an effective technique of urinary diversion associated with
      intermittent catheterization.

PMID- 22657263
TI  - [Results of sacral neuromodulation on the urinary and fecal incontinence and
      sexuality in 20 women suffering from a double incontinence].
AB  - CONTEXT: Urinary and faecal incontinence (defining double incontinence) are
      common conditions, which are frequently associated and can altered sexuality. The
      effectiveness of the sacral nerve modulation (NMS) in the treatment of the urge
      urinary incontinence, faecal incontinence and double incontinence was shown.
      OBJECTIVE: The present article aims to determine the impact of SNM on female
      sexual function in twenty women suffering from a double incontinence. METHODS:
      All patients who received sacral neuromodulation for urge urinary and/or faecal
      incontinence between 2005 and 2010 and who still had the implant were included.
      Only 20 sexually active patients suffering from double incontinence were
      considered eligible. They completed a questionnaire on follow-up examinations.
      RESULTS: The initial indication of NMS was the urge urinary incontinence for 15
      patients and the faecal incontinence for five patients. Ten patients (50%) were
      improved on two incontinence. All patients preserved sexual activity after the
      treatment of NMS. NMS improves the quality of sexual activity in 45% patients.
      The numbers of urinary and faecal episodes of incontinence are decreased
      respectively for 50% and 15% patients during sexual activity. The quality of
      sexual's life and orgasm score are significantly increased in the group of
      patients improved on the DI. CONCLUSION: This study confirms the effectiveness of
      NMS in the treatment of double incontinence which half patients are improved on
      the two incontinence. This study shows that improvement of urinary or faecal
      incontinence could have a positive impact on sexuality of these patients,
      especially for patients improved double incontinence. It is difficult to know if
      these results are related to its direct action on the neurological ways of sexual
      function or on its benefit on the continence.

PMID- 22657264
TI  - [Are therapeutics decisions homogeneous in multidisciplinary onco-urology staff
      meeting? Comparison of therapeutic options taken in four departments from Paris].
AB  - OBJECTIVE: One of the priorities of the "Plan against the Cancer" in France is to
      ensure the discussion of all cancer cases in a multidisciplinary meeting staff
      (RCP). The multidisciplinary collaboration is proposed to guarantee a discussion
      between specialists in every cases, particularly in complex cases. The aim of
      this study was to compare the therapeutic decision taken in four RCP in Paris Ile
      de-France academic centres for three identical cases. MATERIAL: Three cases of
      urological oncology (prostate cancer [PCa], renal cell carcinoma [RCC] and
      bladder tumour) were selected by a single urologist, not involved in further
      discussion. These cases were blindly presented in four academic urology
      department from Paris: Pitie-Salpetriere Hospital, Mondor Hospital, the Georges
      Pompidou European Hospital and Foch Hospital. RESULTS: The four centres met the
      criteria of quality of RCP in terms of multidisciplinarity, frequency and
      standardization. The therapeutic suggestions were similar in the RCC cases, there
      were differences in the surgical approaches and preoperative work-up in the PCa
      case and, lastly, the proposals were different for the bladder cancer case.
      CONCLUSION: The decisions relies on clinical data and preoperative work-up but
      also on the experience and habits of the centre of excellence. For complex cases
      that does not fit with current guidelines, the panel discussion can lead to
      different therapeutic options from a centre to another and is largely influenced
      by the local organisation of the RCP.

PMID- 22657265
TI  - [Primary angiosarcoma of the kidney: case report and literature review].
AB  - The primary angiosarcoma of the kidney is a rare tumor. We report a case of
      angiosarcoma of the right kidney in a man of 60 years. The CT-scan appearance is
      the one of a solid tumor compatible with renal cell carcinoma. Histological
      examination of the piece of nephrectomy straightens diagnosis and reveals the
      angiosarcomatous nature. In this patient with bone and lung synchronous
      metastasis, evolution has been a lightning death in less than three months. The
      literature review confirms the high potential of malignancy of these tumors
      (metastases almost constant and very short survival in spite of local and
      systemic treatment).

PMID- 22657267
TI  - Low-flow, low-gradient aortic stenosis with preserved ejection fraction: still a
      challenging condition.

PMID- 22657266
TI  - Representation of older adults in the late-breaking clinical trials American
      Heart Association 2011 Scientific Sessions.

PMID- 22657268
TI  - Eroding the denominator: the incomplete story of door-to-balloon time reporting.

PMID- 22657269
TI  - Outcome of patients with aortic stenosis, small valve area, and low-flow, low
      gradient despite preserved left ventricular ejection fraction.
AB  - OBJECTIVES: The aim of this case match study was to compare the outcome of
      patients with paradoxical low-flow (left ventricular ejection fraction [LVEF]
      >=50% but stroke volume index <35 ml/m(2)), low-gradient (mean gradient [MG] <40
      mm Hg), a priori severe (aortic valve area [AVA] <=1.0 cm(2)) aortic stenosis
      (AS) (PLG-SAS group) with that of patients with a severe AS (AVA <=1.0 cm(2)) and
      consistent high-gradient (MG >=40 mm Hg) (HG-SAS group) and with that of patients
      with a moderate AS (AVA >1.0 cm(2) and MG <40 mm Hg) (MAS group). BACKGROUND: In
      patients with preserved LVEF, a discordance between the AVA (in the severe range)
      and the gradient (in the moderate range) raises uncertainty with regard to the
      actual severity of the stenosis and thus the therapeutic management of the
      patient. METHODS: In a prospective cohort of AS patients with LVEF >=50%, we
      identified 187 patients in the PLG-SAS group. These patients were retrospectively
      matched: 1) according to the gradient, with 187 patients with MAS; and 2)
      according to the AVA, with 187 patients with HG-SAS. RESULTS: Patients with PLG
      SAS had reduced overall survival (1-year: 89 +/- 2%; 5-year: 64 +/- 4%) compared
      with patients with HG-SAS (1-year: 96 +/- 1%; 5-year: 82 +/- 3%) or MAS (1-year:
      96 +/- 1%; 5-year: 81 +/- 3%). After adjustment for other risk factors, patients
      with PLG-SAS had a 1.71-fold increase in overall mortality and a 2.09-fold
      increase in cardiovascular mortality compared with the 2 other groups. Aortic
      valve replacement was significantly associated with improved survival in the HG
      SAS group (hazard ratio: 0.18; p = 0.001) and in the PLG-SAS group (hazard ratio:
      0.50; p = 0.04) but not in the MAS group. CONCLUSIONS: Prognosis of patients with
      paradoxical low-flow, low-gradient severe AS was definitely worse than those with
      high-gradient severe AS or those with moderate AS. The finding of a low gradient
      cannot exclude the presence of a severe stenosis in a patient with a small AVA
      and preserved LVEF and should mandatorily prompt further investigation.

PMID- 22657270
TI  - Transcatheter aortic valve replacement with the St. Jude Medical Portico valve:
      first-in-human experience.
AB  - OBJECTIVES: The purpose of this study was to demonstrate the feasibility and
      procedural outcomes with a new self-expanding and repositionable transcatheter
      heart valve. BACKGROUND: Transcatheter aortic valve replacement is a viable
      option for selected patients with severe symptomatic aortic stenosis. However,
      suboptimal prosthesis positioning may contribute to paravalvular regurgitation,
      atrioventricular conduction block, and mitral or coronary compromise. METHODS:
      The repositionable Portico valve (St. Jude Medical, Minneapolis, Minnesota) was
      implanted in 10 patients with severe aortic stenosis utilizing percutaneous
      femoral arterial access. Patients underwent transthoracic and transesophageal
      echocardiography and multidetector computed tomography before and after valve
      implantation. Clinical and echocardiographic follow-up was obtained at 30 days.
      RESULTS: Device implantation was successful in all patients. Prosthesis recapture
      and repositioning was performed in 4 patients. Intermittent prosthetic leaflet
      dysfunction in 1 patient required implantation of a second transcatheter valve.
      There was 1 minor stroke. At 30-day follow-up, echocardiographic mean transaortic
      gradient was reduced from 44.9 +/- 16.7 mm Hg to 10.9 +/- 3.8 mm Hg (p < 0.001),
      and valve area increased from 0.6 +/- 0.1 cm(2) to 1.3 +/- 0.2 cm(2) (p < 0.001).
      Paravalvular regurgitation was mild or less in 9 patients (90%) and moderate in 1
      patient (10%). There were no major strokes, major vascular complications, major
      bleeds, or deaths. No patient required pacemaker implantation. All patients were
      in New York Heart Association functional class II or less. CONCLUSIONS:
      Transcatheter aortic valve replacement with the repositionable Portico
      transcatheter heart valve is feasible, with good short-term clinical and
      hemodynamic outcomes.

PMID- 22657271
TI  - SAR matrices: automated extraction of information-rich SAR tables from large
      compound data sets.
AB  - We introduce the SAR matrix data structure that is designed to elucidate SAR
      patterns produced by groups of structurally related active compounds, which are
      extracted from large data sets. SAR matrices are systematically generated and
      sorted on the basis of SAR information content. Matrix generation is
      computationally efficient and enables processing of large compound sets. The
      matrix format is reminiscent of SAR tables, and SAR patterns revealed by
      different categories of matrices are easily interpretable. The structural
      organization underlying matrix formation is more flexible than standard R-group
      decomposition schemes. Hence, the resulting matrices capture SAR information in a
      comprehensive manner. 

PMID- 22657273
TI  - The importance of chronobiology to drug discovery.
AB  - Drug discovery scientists, faced with the myriad challenges involved in
      developing novel therapeutics as medicines, have tended to overlook the question
      of the most beneficial time to administer the drug. Recent developments in our
      understanding of circadian biology and the availability of tools to characterise
      the molecular clock indicate that time and duration of dosing may have profound
      consequences for the efficacy and safety of new and existing therapeutic agents.
      Progress in the field also suggests that many key physiological mechanisms are
      remarkably dependent on the circadian clock. It has also become clear that a
      number of diseases with important unmet medical need display marked circadian
      variation in their symptoms and severity. These discoveries now reveal
      opportunities for new therapeutic strategies to be developed that act by
      modulation of biological rhythms. These novel therapeutic approaches are likely
      to be facilitated by the continuing development of chemical probes and synthetic
      ligands targeted to an increasing number of the key proteins that regulate the
      molecular clock.

PMID- 22657272
TI  - An overiew of non medical prescribing across one strategic health authority: a
      questionnaire survey.
AB  - BACKGROUND: Over 50,000 non-medical healthcare professionals across the United
      Kingdom now have prescribing capabilities. However, there is no evidence
      available with regards to the extent to which non-medical prescribing (NMP) has
      been implemented within organisations across a strategic health authority (SHA).
      The aim of the study was to provide an overview of NMP across one SHA. METHODS:
      NMP leads across one SHA were asked to supply the email addresses of NMPs within
      their organisation. One thousand five hundred and eighty five NMPs were contacted
      and invited to complete an on-line descriptive questionnaire survey, 883 (55.7%)
      participants responded. Data was collected between November 2010 and February
      2011. RESULTS: The majority of NMPs were based in primary care and worked in a
      team of 2 or more. Nurse independent supplementary prescribers were the largest
      group (590 or 68.6%) compared to community practitioner prescribers (198 or
      22.4%), pharmacist independent supplementary prescribers (35 or 4%), and allied
      health professionals and optometrist independent and/or supplementary prescribers
      (8 or 0.9%). Nearly all (over 90%) of nurse independent supplementary prescribers
      prescribed medicines. Approximately a third of pharmacist independent
      supplementary prescribers, allied health professionals, and community
      practitioner prescribers did not prescribe. Clinical governance procedures were
      largely in place, although fewer procedures were reported by community
      practitioner prescribers. General practice nurses prescribed the most items.
      Factors affecting prescribing practice were: employer, the level of experience
      prior to becoming a non-medical prescriber, existence of governance procedures
      and support for the prescribing role (p < 0.001). CONCLUSION: NMP in this
      strategic health authority reflects national development of this relatively new
      role in that the majority of non-medical prescribers were nurses based in primary
      care, with fewer pharmacist and allied health professional prescribers. This
      workforce is contributing to medicines management activities in a range of care
      settings. If non-medical prescibers are to maximise their contribution, robust
      governance and support from healthcare organisations is essential. The continued
      use of supplementary prescribing is questionable if maximum efficiency is sought.
      These are important points that need to be considered by those responsible for
      developing non-medical prescribing in the United Kingdom and other countries
      around the world.

PMID- 22657348
TI  - A functional interaction between the MAGUK protein hDlg and the gap junction
      protein connexin 43 in cervical tumour cells.
AB  - Gap junctions, composed of Cxs (connexins), allow direct intercellular
      communication. Gap junctions are often lost during the development of malignancy,
      although the processes behind this are not fully understood. Cx43 is a widely
      expressed Cx with a long cytoplasmic C-terminal tail that contains several
      potential protein-interaction domains. Previously, in a model of cervical
      carcinogenesis, we showed that the loss of gap junctional communication
      correlated with relocalization of Cx43 to the cytoplasm late in tumorigenesis. In
      the present study, we demonstrate a similar pattern of altered expression for the
      hDlg (human discs large) MAGUK (membrane-associated guanylate kinase) family
      tumour suppressor protein in cervical tumour cells, with partial co-localization
      of Cx43 and hDlg in an endosomal/lysosomal compartment. Relocalization of these
      proteins is not due to a general disruption of cell membrane integrity or Cx
      targeting. Cx43 (via its C-terminus) and hDlg interact directly in vitro and can
      form a complex in cells. This novel interaction requires the N- and C-termini of
      hDlg. hDlg is not required for Cx43 internalization in W12GPXY cells. Instead,
      hDlg appears to have a role in maintaining a cytoplasmic pool of Cx43. These
      results demonstrate that hDlg is a physiologically relevant regulator of Cx43 in
      transformed epithelial cells.

PMID- 22657350
TI  - [Continuous paravertebral analgesia versus intravenous analgesia in minimally
      invasive cardiac surgery by mini-thoracotomy].
AB  - OBJECTIVES: Minimal access cardiac surgery via minithoracotomy aims faster
      recovery and shorter hospital length of stay. Pain control is essential in order
      to achieve this goal. A study was conducted to assess the quality of post
      operative analgesia and complications related to the analgesia techniques after
      cardiac surgery by minithoracotomy. MATERIAL AND METHODS: A descriptive,
      observational and retrospective study was conducted on the patients subjected to
      minimal access cardiac surgery in our centre between the years 2009 to 2011. The
      patients were divided into two groups according to the type of analgesia
      received: analgesia through a paravertebral catheter, with an infusion of local
      anaesthetics (PVB group), and intravenous analgesia with opioids (IOA group). The
      aim of the study was to compare the analgesic quality and the complications
      associated to the analgesic technique, extubation time, post-surgical
      complications, and length of hospital stay between both techniques. RESULTS: A
      total of 37 patients underwent to a modified minimally invasive Heart-Port access
      cardiac surgery. Fifteen patients received analgesia through a paravertebral
      block and the other 22 IV analgesia with opioids. Data are shown as means and
      standard deviation (SD). Mean tracheal extubation time less than 4 hours was
      observed in 60% of the patients in the PVB group, compared to 22% in the IOA
      group (P<.05). Length of stay in ICU for the PVB group was 1.2 (0.7) days
      compared to 2.2 (0.7) days in the IOA group (P<.05). Mean hospital stay was 4.8
      (1.2) days for the PVB group, and 5.6 (2.8) for the IOA group (P>.05. No
      complications associated to the continuous paravertebral block were observed.
      DISCUSSION: PVB analgesia is an acceptable safe technique in cardiac surgery via
      thoracotomy which enables early extubation with optimal pain control when
      compared with IV analgesia with opioids.

PMID- 22657351
TI  - [Salmonella enteritidis bacteraemia as clinical onset of acquired immune
      deficiency syndrome].
AB  - The case is presented of a 38 year-old patient who was admitted in the Emergency
      Department due to a severe acute respiratory failure and who was transferred to
      the Critical Care Unit with a suspected initial diagnosis of community acquired
      pneumonia caused by an atypical microorganism, which was complicated with an
      acute respiratory distress syndrome. This was able to be treated with non
      invasive mechanical ventilation. At 48 hours after admission, the growth of Gram
      negative bacilli in the blood culture was reported, which was subsequently
      identified as Salmonella enteritidis. This information, along with the
      lymphopenia suffered by the patient, suggested an immunodepressed state, thus
      serological tests were performed which showed positive for HIV. Antibiotic
      treatment was started based on the microbiological findings, with a favourable
      clinical outcome for the patient.

PMID- 22657352
TI  - [Perioperative tumour dissemination. 2. Effects of anaesthesia and analgesia].
AB  - There has been growing concern over the last few years on the effect that the
      anaesthetic drugs used during oncological surgery could have on long-term tumour
      progression. In laboratory studies, it has been observed how some substances used
      during the anaesthetic procedure influence tumour immunosurveillance, cell
      proliferation or tumour angiogenesis processes. The possible clinical relevance
      of the anaesthetic technique used as regards long-term tumour progression and
      survival is still to be determined. However, based on retrospective studies, it
      appears that those anaesthetic techniques combined with the use of regional
      anaesthesia and analgesia may be beneficial compared to those that are maintained
      on the use of opioids. Further research should help to clarify the long-term
      clinical relevance of the anaesthetic process during oncological surgery.

PMID- 22657349
TI  - Mitochondrial redox signaling: Interaction of mitochondrial reactive oxygen
      species with other sources of oxidative stress.
AB  - SIGNIFICANCE: Oxidative stress is a well established hallmark of cardiovascular
      disease and there is strong evidence for a causal role of reactive oxygen and
      nitrogen species (RONS) therein. RECENT ADVANCES: Improvement of cardiovascular
      complications by genetic deletion of RONS producing enzymes and overexpression of
      RONS degrading enzymes proved the involvement of these species in cardiovascular
      disease at a molecular level. Vice versa, overexpression of RONS producing
      enzymes as well as deletion of antioxidant enzymes was demonstrated to aggravate
      cardiovascular complications. CRITICAL ISSUES: With the present overview we
      present and discuss different pathways how mitochondrial RONS interact
      (crosstalk) with other sources of oxidative stress, namely NADPH oxidases,
      xanthine oxidase and an uncoupled nitric oxide synthase. The potential mechanisms
      of how this crosstalk proceeds are discussed in detail. Several examples from the
      literature are summarized (including hypoxia, angiotensin II mediated vascular
      dysfunction, cellular starvation, nitrate tolerance, aging, hyperglycemia, beta
      amyloid stress and others) and the underlying mechanisms are put together to a
      more general concept of redox-based activation of different sources of RONS via
      enzyme-specific "redox switches". Mitochondria play a key role in this concept
      providing redox triggers for oxidative damage in the cardiovascular system but
      also act as amplifiers to increase the burden of oxidative stress. FUTURE
      DIRECTIONS: Based on these considerations, the characterization of the role of
      mitochondrial RONS formation in cardiac disease as well as inflammatory processes
      but also the role of mitochondria as potential therapeutic targets in these
      pathophysiological states should be addressed in more detail in the future.

PMID- 22657353
TI  - [Anesthesic managing in Berdon's syndrome].

PMID- 22657354
TI  - Sybron.

PMID- 22657355
TI  - Martek instruments, inc.

PMID- 22657356
TI  - Fifth annual symposium on environmental epidemiology.

PMID- 22657357
TI  - The name of the game.

PMID- 22657358
TI  - Washington.

PMID- 22657359
TI  - International.

PMID- 22657360
TI  - Science.

PMID- 22657361
TI  - Viewpoint.

PMID- 22657362
TI  - Award.

PMID- 22657363
TI  - States.

PMID- 22657364
TI  - Business.

PMID- 22657365
TI  - Technology.

PMID- 22657366
TI  - Phasing out PCBs.

PMID- 22657367
TI  - Recent reports on the greenhouse effect.

PMID- 22657369
TI  - Dechlorination of wastewater and cooling water.

PMID- 22657371
TI  - verlag chemie international.

PMID- 22657370
TI  - Disposal of hazardous elemental wastes.

PMID- 22657372
TI  - Products.

PMID- 22657373
TI  - ThomasTM scientific.

PMID- 22657374
TI  - The environmental protection energy.

PMID- 22657375
TI  - Canberra industries, inc.

PMID- 22657376
TI  - Dionex.

PMID- 22657377
TI  - Literature.

PMID- 22657378
TI  - Classified section.

PMID- 22657380
TI  - professional consulting services directory.

PMID- 22657381
TI  - Current Research Author's Guide.

PMID- 22657382
TI  - Editorial policy.

PMID- 22657383
TI  - Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism
      with cardiovascular disease in patients with rheumatoid arthritis.
AB  - OBJECTIVE: The methionine sulfoxide reductase A (MSRA) gene is related to
      oxidative stress that has been involved in the susceptibility to rheumatoid
      arthritis (RA) in genome-wide pathway analysis and replication studies. The aim
      of the present study was to determine whether the MSRA gene is implicated in
      susceptibility to cardiovascular (CV) disease in RA patients. METHODS: A total of
      1302 patients fulfilling the 1987 American College of Rheumatism classification
      criteria for RA were genotyped for the MSRA rs10903323 (G/A) polymorphism. Two
      hundred and thirty-three (17.9%) patients experienced CV events. Human leucocyte
      antigen (HLA)-DRB1 genotyping was performed using molecular-based methods.
      Multiple logistic regression models were constructed with adjustments for gender,
      age at RA diagnosis, follow-up, rheumatoid shared epitope, and traditional CV
      risk as potential confounders. RESULTS: There were no statistically significant
      differences in the allele or genotype frequencies for the MSRA rs10903323
      polymorphism between RA patients who experienced CV events and those who did not.
      However, an adjusted logistic regression model disclosed that the minor allele G
      yielded a marginally significant increased risk of CV events in this series of
      patients with RA [p = 0.05, odds ratio (OR) 1.68, 95% confidence interval (CI)
      1.00-2.85]. When the logistic regression model was adjusted for anti-cyclic
      citrullinated peptide (anti-CCP) antibody status instead of for shared epitope,
      an increased risk of having ischaemic heart disease was found in patients
      carrying the minor allele G (p = 0.04, OR 2.00, 95% CI 1.03-3.88). CONCLUSION:
      The MSRA rs10903323 gene polymorphism may be implicated in the increased risk to
      develop CV events, in particular ischaemic heart disease, observed in RA
      patients.

PMID- 22657384
TI  - Changes in the criticality of Hopf bifurcations due to certain model reduction
      techniques in systems with multiple timescales.
AB  - A major obstacle in the analysis of many physiological models is the issue of
      model simplification. Various methods have been used for simplifying such models,
      with one common technique being to eliminate certain 'fast' variables using a
      quasi-steady-state assumption. In this article, we show when such a physiological
      model reduction technique in a slow-fast system is mathematically justified. We
      provide counterexamples showing that this technique can give erroneous results
      near the onset of oscillatory behaviour which is, practically, the region of most
      importance in a model. In addition, we show that the singular limit of the first
      Lyapunov coefficient of a Hopf bifurcation in a slow-fast system is, in general,
      not equal to the first Lyapunov coefficient of the Hopf bifurcation in the
      corresponding layer problem, a seemingly counterintuitive result. Consequently,
      one cannot deduce, in general, the criticality of a Hopf bifurcation in a slow
      fast system from the lower-dimensional layer problem.

PMID- 22657386
TI  - Intramedullary spinal cord metastasis from prostate carcinoma: a case report.
AB  - INTRODUCTION: Although vertebral and epidural metastases are common, intradural
      metastases and intramedullary spinal cord metastases are rare. The indications
      for the treatment of intramedullary spinal cord metastases remain controversial.
      We present the first biopsy-proven case of an intramedullary spinal cord
      metastasis from adenocarcinoma of the prostate. CASE PRESENTATION: Our patient
      was a 68-year-old right-handed Caucasian man with a Gleason grade 4 + 3 prostate
      adenocarcinoma who had previously undergone a prostatectomy, androgen blockade
      and transurethral debulking. He presented with new-onset saddle anesthesia and
      fecal incontinence. Magnetic resonance imaging demonstrated a spindle-shaped
      intramedullary lesion of the conus medullaris. Our patient underwent
      decompression and an excisional biopsy; the lesion's pathology was consistent
      with metastatic adenocarcinoma of the prostate. Postoperatively, our patient
      received CyberKnife(r) radiosurgery to the resection cavity at a marginal dose of
      27Gy to the 85% isodose line. At three months follow-up, our patient remains
      neurologically stable with no new deficits or lesions. CONCLUSIONS: We review the
      literature and discuss the indications for surgery and radiosurgery for
      intramedullary spinal cord metastases. We also report the novel use of
      stereotactic radiosurgery to sterilize the resection cavity following an
      excisional biopsy of the metastasis.

PMID- 22657385
TI  - Encapsulation of basic fibroblast growth factor by polyelectrolyte multilayer
      microcapsules and its controlled release for enhancing cell proliferation.
AB  - Basic fibroblast growth factor (FGF2) is an important protein for cellular
      activity and highly vulnerable to environmental conditions. FGF2 protected by
      heparin and bovine serum albumin was loaded into the microcapsules by a
      coprecipitation-based layer-by-layer encapsulation method. Low cytotoxic and
      biodegradable polyelectrolytes dextran sulfate and poly-L-arginine were used for
      capsule shell assembly. The shell thickness-dependent encapsulation efficiency
      was measured by enzyme-linked immunosorbent assay. A maximum encapsulation
      efficiency of 42% could be achieved by microcapsules with a shell thickness of 14
      layers. The effects of microcapsule concentration and shell thickness on
      cytotoxicity, FGF2 release kinetics, and L929 cell proliferation were evaluated
      in vitro. The advantage of using microcapsules as the carrier for FGF2 controlled
      release for enhancing L929 cell proliferation was analyzed.

PMID- 22657387
TI  - Linking health information technology to patient safety and quality outcomes: a
      bibliometric analysis and review.
AB  - OBJECTIVE: To assess the scholarly output of grants funded by the Agency for
      Healthcare Research and Quality (AHRQ) that published knowledge relevant to the
      impact of health information technologies on patient safety and quality of care
      outcomes. STUDY DESIGN: We performed a bibliometric analysis of the identified
      scholarly articles, their journals, and citations. In addition, we performed a
      qualitative review of the full-text articles and grant documents. DATA
      COLLECTION/EXTRACTION METHODS: Papers published by AHRQ-funded investigators were
      retrieved from MEDLINE, journal impact factors were extracted from the 2010
      Thompson Reuters Journal Citation Report, citations were retrieved from ISI's Web
      of Knowledge and Google Scholar. PRINCIPAL FINDINGS: Seventy-two articles met the
      criteria for review. Most articles addressed one or more of AHRQ's outcome goals
      and focus priorities. The average impact factor for the journals was 4.005
      (range: 0.654-28.899). The articles, and their respective grants, represented a
      broad range of health information technologies. CONCLUSIONS: This set of AHRQ
      funded research projects addressed the goals and priorities of AHRQ, indicating
      notable contributions to the scientific knowledge base on the impact of
      information system use in healthcare.

PMID- 22657388
TI  - Effect of water structure on gelation of agar in glycerol solutions and phase
      diagram of agar organogels.
AB  - A comprehensive study of hydration of polyanionic agar molecules in its solution
      and gel phase in glycerol-water binary solvent is reported. Raman spectroscopy
      results predict differential water structure arrangement for glycerol-water
      binary solvent, 0.02% (w/v) agar in glycerol solution and 0.3% (w/v) agar
      organogel. The 3200 cm(-1) Raman band pertaining to ice-like structure of water
      was found to increase in gel phase alike in glycerol-water solvent while it
      decreased in agar solutions with increase in glycerol concentration. In contrast,
      the partially structured water corresponding to the component 3310 cm(-1) of
      Raman spectra increased in agar solution, and decreased in gel phase similar to
      glycerol-water solvent case. We have explained these observations based on a
      simple model where the available oxygen to hydrogen atom ratio in a given solvent
      polymer system uniquely defines hydration in solution and gel phases. The
      gelation concentration was found to increase from 0.18 (for water) to 0.22% (w/v)
      (50% v/v glycerol solution) as the glycerol concentration was raised.
      Correspondingly, the gelation temperature, T(g), showed a decline from 40 to 20 
      degrees C, and the gel melting temperature, T(m), revealed a reduction from 81 to
      65  degrees C in the same glycerol concentration regime. Two distinctive features
      are evident here: (i) presence of glycerol as a cosolvent does not favor the
      gelation of agar as compared to water and (ii) agar organogels are softer than
      their hydrogels. A unique 3D phase diagram for the agar organogel is proposed.
      Circular dichroism data confirmed that the agar molecules retained their
      biological activity in these solvents. Thus, it is shown that thermo-mechanical
      properties of these organogels could be systematically tuned and adapted as per
      application requirement.

PMID- 22657389
TI  - Genomic analysis of fetal nucleic acids in maternal blood.
AB  - The 15 years since the discovery of fetal DNA in maternal plasma have witnessed
      remarkable developments in noninvasive prenatal diagnosis. An understanding of
      biological parameters governing this phenomenon, such as the concentration and
      molecular size of circulating fetal DNA, has guided its diagnostic applications.
      Early efforts focused on the detection of paternally inherited sequences, which
      were absent in the maternal genome, in maternal plasma. Recent developments in
      precise measurement technologies such as digital polymerase chain reaction (PCR)
      have allowed the detection of minute allelic imbalances in plasma and have
      catalyzed analysis of single-gene disorders such as the hemoglobinopathies and
      hemophilia. The advent of massively parallel sequencing has enabled the robust
      detection of fetal trisomies in maternal plasma. Recent proof-of-concept studies
      have detected a chromosomal translocation and a microdeletion and have deduced a
      genome-wide genetic map of a fetus from maternal plasma. Understanding the
      ethical, legal, and social aspects in light of such rapid developments is thus a
      priority for future research.

PMID- 22657390
TI  - A comparative genomics approach to understanding transmissible cancer in
      Tasmanian devils.
AB  - A fatal contagious cancer is driving an entire species to extinction. Comparative
      genomics will unravel the origin and evolution of devil facial tumor disease
      (DFTD). The DFTD allograft arose from a Schwann cell in a female Tasmanian devil
      more than 15 years ago; since then, the tumor has passed through at least 100,000
      hosts, evolving and mutating along the way. Tumor genome sequencing and molecular
      cytogenetic technologies now allow direct comparisons of candidate genes involved
      in tumorigenesis in human cancers. As a stable transmissible cancer, DFTD
      provides unique insights into cancer development, progression, and immune evasion
      and is likely to help increase our understanding of human cancer. In addition,
      these studies provide hope for discoveries of drug targets or vaccine candidates
      that will prevent the extinction of this iconic Australian marsupial.

PMID- 22657391
TI  - Human genetic individuality.
AB  - The central preoccupation of human genetics is an effort to understand the
      genotypic basis of human phenotypic diversity. Although recent progress in
      identifying the genes that, when mutated, underlie major genetic diseases has
      been rapid, knowledge of the genetic influences on the vast range of variable,
      and at least partially heritable, traits that constitute the "normal" range of
      human phenotypic variation lags. Spectacular advances in our knowledge of human
      genetic variation have laid the groundwork for a synthesis of insights from
      medical genetics, population genetics, molecular evolution, and the study of
      human origins that places basic constraints on models of human genetic
      individuality. Balancing selection, local adaptation, mutation-selection balance,
      and founder effects have all extensively shaped contemporary genetic variation.
      Long-term-balancing selection appears largely to reflect the consequences of host
      pathogen arms races. Local adaptation has been widespread-and involved responses
      to a plethora of selective pressures, some identifiable but most unknown.
      However, it appears to be a combination of mutation-selection balance and founder
      effects that largely accounts for genetic individuality. If true, this inference
      has major implications for future research programs in human genetics.

PMID- 22657392
TI  - Biomechancial quantification of pathologic manipulable spinal lesions: an in vivo
      ovine model of spondylolysis and intervertebral disc degeneration.
AB  - OBJECTIVE: The purposes of this study were to quantify the biomechanical and
      pathologic consequences of surgically induced spinal lesions and to determine
      their response to spinal manipulation (SMT) in an in vivo ovine model. METHODS:
      Of 24 Merino sheep, 6 received L5 spondylolytic defects, 6 received L1 annular
      lesions, and 12 served as respective controls. Dorsoventral (DV) stiffness was
      assessed using oscillatory loads (2-12 Hz). Two SMT force-time profiles were
      administered in each of the groups using a randomized and repeated-measures
      design. Stiffness and the effect of SMT on the DV motions and multifidus needle
      electromyographic responses were assessed using a repeated-measures analysis of
      variance (alpha = .05). Postmortem histologic analysis and computed tomography
      validated the presence of lesions. RESULTS: L5 DV stiffness was significantly
      increased (40.2%) in the spondylolysis (6.28 N/mm) compared with the L5 control
      group (4.48 N/mm) (P < 03). Spinal manipulations delivered to the spondylolysis
      group resulted in less DV vertebral displacement (P < .01) compared with
      controls. Dorsoventral stiffness of the disc degeneration group was 5.66 N/mm,
      94.5% greater than in the L1 control group (2.91 N/mm) (P < .01). One hundred
      millisecond SMTs resulted in significantly reduced DV displacements in the disc
      degeneration group compared with the L1 control group (P < .01). Animals in the
      disc degeneration group showed a consistent 25% to 30% reduction in needle
      electromyographic responses to all SMTs. CONCLUSIONS: Quantifiable objective
      evidence of spinal lesions and their response to SMT were confirmed in this
      study. Neuromechanical alterations provide novel insights into quantifying
      manipulable spinal lesions and a means to biomechanically assess SMT outcomes.

PMID- 22657393
TI  - Characterization of hydrophobic-ligand-binding proteins of Taenia solium that are
      expressed specifically in the adult stage.
AB  - Taenia solium, a causative agent of taeniasis and cysticercosis, has evolved a
      repertoire of lipid uptake mechanisms. Proteome analysis of T. solium excretory
      secretory products (TsESP) identified 10 kDa proteins displaying significant
      sequence identity with cestode hydrophobic-ligand-binding-proteins (HLBPs). Two
      distinct 362- and 352-bp-long cDNAs encoding 264- and 258-bp-long open reading
      frames (87 and 85 amino acid polypeptides) were isolated by mining the T. solium
      expressed sequence tags and a cDNA library screening (TsHLBP1 and TsHLBP2; 94%
      sequence identity). They clustered into the same clade with those found in
      Moniezia expansa and Hymenolepis diminuta. Genomic structure analysis revealed
      that these genes might have originated from a common ancestor. Both the crude
      TsESP and bacterially expressed recombinant proteins exhibited binding activity
      toward 1-anilinonaphthalene-8-sulfonic acid (1,8-ANS), which was competitively
      inhibited by oleic acid. The proteins also bound to cis-parinaric acid (cPnA) and
      16-(9-anthroyloxy) palmitic acid (16-AP), but showed no binding activity against
      11-[(5-dimethylaminonaphthalene-1-sulfonyl) amino] undecanoic acid (DAUDA) and
      dansyl-DL-alpha-aminocaprylic acid (DACA). Unsaturated fatty acids (FAs) showed
      greater affinity than saturated FAs. The proteins were specifically expressed in
      adult worms throughout the strobila. The TsHLBPs might be involved in uptake
      and/or sequestration of hydrophobic molecules provided by their hosts, thus
      contributing to host-parasite interface interrelationships.

PMID- 22657394
TI  - Comparison of chronic kidney disease and risk for presenting with painless versus
      nonpainless acute myocardial infarction.
AB  - Chronic kidney disease increases the risk for developing ischemic heart disease,
      but it has not been well known whether it also affects the manifestation of
      painless acute myocardial infarction (AMI), which has important clinical
      implications. The aim of this study was to identify whether chronic kidney
      disease is associated with the presentation of painless AMI. A total of 2,656
      consecutively hospitalized patients with AMI from January 2008 to February 2012
      were enrolled. Estimated glomerular filtration rate (eGFR) was calculated using
      calibrated serum creatinine and the abbreviated Modification of Diet in Renal
      Disease (MDRD) equation. Patient clinical characteristics, angiographic findings,
      and the use of medications were reviewed. Multivariate logistic regression
      analysis was used to examine the association of reduced eGFR and presentation
      with painless AMI. A total of 2,176 adults with painful AMI and 480 adults with
      painless AMI were studied, and baseline eGFR was calculated. Mean eGFR was lower
      in subjects with painless AMI compared to those with painful AMI. Compared to an
      eGFR >90 ml/min/1.73 m(2), a strong, graded, independent association was observed
      between reduced eGFR and presentation with painless AMI, with adjusted odds
      ratios of 1.65 (95% confidence interval 1.16 to 2.36) for an eGFR of 60 to 89
      ml/min/1.73 m(2), 2.92 (95% confidence interval 1.89 to 4.52) for an eGFR of 45
      to 59 ml/min/1.73 m(2), and 3.44 (95% confidence interval 2.20 to 5.38) for an
      eGFR <45 ml/min/1.73 m(2). In conclusion, lower eGFR was a strong, independent
      predictor of presentation with painless AMI versus painful AMI.

PMID- 22657395
TI  - Does ED crowding decrease the number of procedures a physician in training
      performs? A prospective observational study.
AB  - PURPOSE: The aim of the study was to determine whether the number of procedures
      performed by residents and medical students in the emergency department (ED) is
      affected by ED crowding. METHODS: In this single-center, prospective,
      observational study, standardized data collection forms were completed by both
      trainees and supervising emergency physicians (EPs) at the end of each ED shift
      from August 2009 to March 2010. Shifts with no trainees were excluded. All
      procedures that were offered to a trainee were recorded as well as the number of
      potential ED procedures that were, instead, referred to a consulting service.
      Emergency department crowding was measured in 2 ways: ED length of stay (LOS) and
      the EP's assessment of crowding during the shift. Poisson regression was used to
      assess the adjusted effect of ED crowding on the number of trainee procedures
      performed as well as on the number of procedures given away. RESULTS: There were
      804 procedures performed by 113 trainees during 647 trainee shifts. Medical
      students comprised 51% of trainees. Median number of procedures performed per
      shift was 1.0 (Fine interquartile range, 0-2.0). Emergency department crowding
      was not associated with the adjusted number of procedures trainees performed
      using either the EP's assessment of crowding (P = .52) or ED LOS (P = .84).
      Emergency department crowding was associated with an adjusted 256% increase in
      the mean number of procedures given away (P = .02) when measured using physician
      assessment but was not associated with crowding when assessed using ED LOS (P =
      .06). CONCLUSIONS: Crowding was not significantly associated with the number of
      procedures availed to ED trainees. In patients being considered for admission,
      however, when the managing EP felt that it was crowded, there was an association
      with giving procedures to consulting services.

PMID- 22657396
TI  - Risk stratification in acute pulmonary embolism: what does gamma-glutamyl
      transferase add?

PMID- 22657397
TI  - Compartment syndrome on a patient's forearm related to carbon monoxide poisoning.
AB  - Carbon monoxide (CO) is a colorless, odorless, nonirritating, toxic gas produced
      by the incomplete oxidation of hydrocarbons. Common sources of CO include motor
      vehicles, house fires, furnaces/heaters, and wood-burning stoves. It is a serious
      health problem resulting in approximately 50,000 visits to the emergency
      department and is responsible for 3500 deaths annually in the United States.
      Besides accidental exposure, CO is also one of the leading causes of death by
      suicide. In the present study, we discuss compartment syndrome caused by CO
      poisoning in a 15-year-old boy. To our knowledge, this is the first CO poisoning
      case causing compartment syndrome.

PMID- 22657398
TI  - Four-dimensional structure-activity relationship model to predict HIV-1 integrase
      strand transfer inhibition using LQTA-QSAR methodology.
AB  - Despite highly active antiretroviral therapy (HAART) implementation, there is a
      continuous need to search for new anti-HIV agents. HIV-1 integrase (HIV-1 IN) is
      a recently validated biological target for AIDS therapy. In this work, a four
      dimensional quantitative structure-activity relationship (4D-QSAR) study using
      the new methodology named LQTA-QSAR approach with a training set of 85 HIV-1 IN
      strand transfer inhibitors (INSTI), containing the beta-diketo acid (DKA)
      substructure, was carried out. The GROMACS molecular dynamic package was used to
      obtain a conformational ensemble profile (CEP) and LQTA-QSAR was employed to
      calculate Coulomb and Lennard-Jones potentials and to generate the field
      descriptors. The partial least-squares (PLS) regression model using 14 field
      descriptors and 8 latent variables (LV) yielded satisfactory statistics (R2=
      0.897, SEC = 0.270, and F = 72.827), good performance in internal (QLOO2 = 0.842
      and SEV = 0.314) and external prediction (Rpred2 = 0.839, SEP = 0.384, AREpred =
      4.942%, k = 0.981, k' = 1.016, and |R02 - R0'2 = 0.0257). The QSAR model was
      shown to be robust (leave-N-out cross validation; average QLNO2 = 0.834) and was
      not built by chance (y-randomization test; R2 intercept = 0.109; Q2 intercept = 
      0.398). Fair chemical interpretation of the model could be traced, including
      descriptors related to interaction with the metallic cofactors and the
      hydrophobic loop. The model obtained has a good potential for aid in the design
      of new INSTI, and it is a successful example of application of LQTA-QSAR as an
      useful tool to be used in computer-aided drug design (CADD).

PMID- 22657399
TI  - Estimate at your peril: imputation methods for patient withdrawal can bias
      efficacy outcomes in chronic pain trials using responder analyses.

PMID- 22657400
TI  - Laser heat stimulation of tiny skin areas adds valuable information to
      quantitative sensory testing in postherpetic neuralgia.
AB  - Patients suffering from postherpetic neuralgia often complain about hypo- or
      hypersensation in the affected dermatome. The loss of thermal sensitivity has
      been demonstrated by quantitative sensory testing as being associated with small
      fiber (Adelta- and C-fiber) deafferentation. We aimed to compare laser
      stimulation (radiant heat) to thermode stimulation (contact heat) with regard to
      their sensitivity and specificity to detect thermal sensory deficits related to
      small-fiber dysfunction in postherpetic neuralgia. We contrasted detection rate
      of laser stimuli with 5 thermal parameters (thresholds of cold/warm detection,
      cold/heat pain, and sensory limen) of quantitative sensory testing. Sixteen
      patients diagnosed with unilateral postherpetic neuralgia and 16 age- and gender
      matched healthy control subjects were tested. Quantitative sensory testing and
      laser stimulation of tiny skin areas were performed in the neuralgia-affected
      skin and in the contralateral homologue of the neuralgia-free body side. Across
      the 5 thermal parameters of thermode stimulation, only one parameter (warm
      detection threshold) revealed sensory abnormalities (thermal hypoesthesia to warm
      stimuli) in the neuralgia-affected skin area of patients but not in the
      contralateral area, as compared to the control group. In contrast, patients
      perceived significantly less laser stimuli both in the affected skin and in the
      contralateral skin compared to controls. Overall, laser stimulation proved more
      sensitive and specific in detecting thermal sensory abnormalities in the
      neuralgia-affected skin, as well as in the control skin, than any single thermal
      parameter of thermode stimulation. Thus, laser stimulation of tiny skin areas
      might be a useful diagnostic tool for small-fiber dysfunction.

PMID- 22657401
TI  - Parents who catastrophize about their child's pain prioritize attempts to control
      pain.
AB  - How parents respond to their child in pain is critically important to how both
      parent and child attempt to cope with pain. We examined the influence of parental
      catastrophic thinking about child pain on their prioritization for pain control.
      Using a vignette methodology, parents reported, in response to different pain
      scenarios, on their imagined motivation for 2 competing goals: to control their
      child's pain (ie, pain control) or to encourage their child's participation in
      daily activities (ie, activity engagement). The effects of parent gender, pain
      intensity, and duration on parental goal priority were also explored. Findings
      indicated that higher levels of parental catastrophic thoughts were associated
      with the parents prioritizing child pain control over activity engagement. This
      effect was significantly moderated by pain duration. Specifically, pain control
      was more of a priority for those high in catastrophic thinking when the pain was
      more acute. In contrast, parental catastrophic thoughts had no effect on the pain
      control strategy favored by parents in situations with longer-lasting pain.
      Furthermore, independently of parental catastrophic thoughts, heightened priority
      for pain control was observed in highly intense and chronic pain situations.
      Moreover, in highly intense pain, priority for pain control was stronger for
      mothers compared with fathers. Theoretical and clinical implications and
      directions for future research are discussed.

PMID- 22657402
TI  - Safety of stent placement in recurrent or persistent esophageal cancer after
      definitive chemoradiotherapy: a case series.

PMID- 22657403
TI  - Esophageal function testing.

PMID- 22657404
TI  - Outcomes of EMR of defiant colorectal lesions directed to an endoscopy referral
      center.
AB  - BACKGROUND: Flat and sessile lesions are being identified more frequently because
      of increased awareness, improved endoscopic skills, and enhanced imaging. The
      defiant polyp (DP) is a lesion identified at colonoscopy that defies resection by
      the standard snare polypectomy technique. Increasingly, the DP undergoes
      photodocumentation and tissue sampling, and the patient is referred for an
      attempt at curative colonoscopic resection. OBJECTIVE: To evaluate the current
      nature of the DPs and outcomes of their endoscopic resection. DESIGN:
      Retrospective study. SETTING: Tertiary referral center. PATIENTS AND
      INTERVENTIONS: Patients with colorectal polyps not amenable to standard snare
      polypectomy were referred to a single endoscopist at a tertiary center for an
      attempt at curative endoscopic resection. The indication DP was applied
      prospectively, as defined previously, beginning in June 2007. An electronic
      endoscopy report database was searched for this indication from June 2007 to
      October 2009 for a single endoscopist at an endoscopy referral center. Data
      pertaining to patient age and sex, polyp site and histopathology, resection
      technique, use of adjunctive ablation, adverse events, and residual/recurrent
      neoplasia at follow-up were culled. Submucosal injection of varying quantities of
      normal saline solution tinted with methylene blue dye was used for endoscopic
      resection. Standard and mini-snares were used with pure coagulation current. MAIN
      OUTCOME MEASUREMENTS: Complete resection, complications, recurrence. RESULTS:
      This study included 274 patients (50.4% women, age 65 [standard deviation 12]
      years) with a total of 315 DPs who were referred for attempted endoscopic
      resection. The majority of DPs were located in the right side of the colon (226;
      72%). The mean size was estimated at 23 mm (range 8-100 mm; standard deviation
      13). In 29 DPs (10%), surgery was required because endoscopic resection was
      deemed unsuitable because of the unfavorable appearance (n = 3), the location (n
      = 9), or the inability to lift (n = 10) or because of submucosal invasion on post
      EMR histopathology (n = 7). Complete endoscopic eradication (R0) was achieved in
      a single session in 286 DPs (91%). En bloc resection was performed in 153 polyps
      (53.5%) and piecemeal resection in 132 (46%). Histopathology revealed 178 tubular
      adenomas (56.5%), 62 serrated adenomas (20%), 27 tubulovillous adenomas (9%), 10
      hyperplastic polyps (3%), and 14 adenocarcinomas (4.5%). Adjunctive ablation of
      focal residual neoplastic tissue was applied in 69 DPs (24%) to achieve R0.
      Procedure-related adverse events were recorded in 29 of 249 patients (11.6%).
      Acute bleeding occurred in 9 patients (1 required hospitalization and repeat
      endoscopy). There was 1 microperforation managed with clip closure and
      antibiotics. Delayed bleeding (1-6 days post-procedure) was observed in 18
      patients (7.2%), of whom 8 required hospitalization and 4 colonoscopy for
      hemostasis. Among the patients who underwent follow-up surveillance colonoscopy
      (135 of 258 patients), residual/recurrent neoplastic tissue at the site of the
      previous EMR was identified in 36 (27%). Residual/recurrent neoplasia was
      successfully eradicated with further endoscopic resection or ablation.
      LIMITATIONS: A retrospective design. CONCLUSIONS: DPs consist predominantly of
      sessile and flat adenomas including serrated adenomas. Most DPs can be
      successfully eradicated at dedicated therapeutic colonoscopy by using adjunctive
      resection and ablation techniques. The R0 rate is high and the adverse event rate
      is low. A relatively high rate of local residual/recurrent neoplasia at the
      resection site underscores the importance of follow-up colonoscopy.

PMID- 22657405
TI  - TH17 and TH22 cells: a confusion of antimicrobial response with tissue
      inflammation versus protection.
AB  - Substantial progress in understanding mechanisms of immune regulation in allergy,
      asthma, autoimmune diseases, tumors, organ transplantation, chronic infections,
      and pregnancy is in an exciting developmental phase that might lead to a variety
      of targeted therapeutic approaches. Recent progress in the interaction between
      immune/inflammatory cell subsets through cytokines, particularly the extension of
      the knowledge on reciprocal regulation and counterbalance between subsets of
      T(H)1, T(H)2, T(H)9, T(H)17, T(H)22, T follicular helper cells and different
      subsets of regulatory T cells, as well as corresponding and co-orchestrating B
      cell, natural killer cell, dendritic cell, and innate lymphoid cell subsets,
      offers new possibilities for immune intervention. Studies on new subsets confirm
      the important role of T cells in the instruction of tissue cells and also
      demonstrate the important role of feedback regulation for the polarization toward
      distinct T-cell subsets. T(H)17 and T(H)22 cells are 2 emerging T(H) cell subsets
      that link the immune response to tissue inflammation; IL-17A and IL-17F and IL-22
      are their respective prototype cytokines. Although both cytokines play roles in
      immune defense to extracellular bacteria, IL-17 augments inflammation, whereas IL
      22 plays a tissue-protective role. This review focuses on current knowledge on
      T(H)17 and T(H)22 cells and their role in inflammation, with special focus on the
      mechanisms of their generation and driving and effector cytokines, as well as
      their role in host defense, autoimmunity, and allergic diseases.

PMID- 22657407
TI  - Rhinovirus 16-induced IFN-alpha and IFN-beta are deficient in bronchoalveolar
      lavage cells in asthmatic patients.
AB  - BACKGROUND: Asthmatic patients have defective rhinovirus-induced IFN-beta and IFN
      lambda production from bronchial epithelial cells and IFN-lambda from
      bronchoalveolar lavage (BAL) cells. Whether bronchoalveolar lavage cells have
      defective type I interferon responses to rhinovirus is unknown, as are mechanisms
      explaining defective rhinovirus interferon induction in asthmatic patients.
      OBJECTIVE: We sought to investigate rhinovirus induction of type I interferons in
      BAL and blood mononuclear cells from asthmatic patients and healthy subjects and
      to investigate mechanisms of any deficiency observed. METHODS: BAL and blood
      mononuclear cells from atopic asthmatic patients and healthy subjects were
      infected with rhinovirus ex vivo. Interferon proteins were analyzed by using
      ELISA. mRNA expression of key components of interferon induction pathways were
      analyzed by using quantitative PCR. RESULTS: Rhinovirus induction of type I
      interferon protein was delayed and deficient in BAL cells from asthmatic
      patients, and lower interferon levels were associated with greater airway
      hyperresponsiveness and skin prick test response positivity. Expression of Toll
      like receptor (TLR) 3, TLR7, TLR8, retinoic acid-inducible gene I (RIG-I),
      melanoma differentiation-associated gene 5 (MDA-5), TIR domain-containing adapter
      inducing IFN-beta (TRIF), myeloid differentiation primary response gene 88
      (MyD88), caspase recruitment domain adaptor inducing IFN-beta (CARDIF), IL-1
      receptor-associated kinase 4 (IRAK4), IkappaB kinase beta (IKKB), IkappaB kinase
      iota (IKKI), interferon regulatory factors 3 and 7, and rhinovirus induction of
      expression of the virus-inducible molecules TLR3, TLR7, RIG-I, and MDA-5 were not
      impaired in these interferon-deficient BAL cells in asthmatic patients. Defective
      rhinovirus interferon induction was not observed in blood mononuclear cells.
      CONCLUSIONS: Rhinovirus induction of type I interferons in BAL cells is delayed
      and deficient and might be a marker of more severe asthma. Defective rhinovirus
      interferon induction in asthmatic patients was not accompanied by differences in
      the expression or induction of key molecules implicated in viral induction of
      interferons.

PMID- 22657408
TI  - The ANO3/MUC15 locus is associated with eczema in families ascertained through
      asthma.
AB  - BACKGROUND: A previous genome-wide linkage scan in 295 families of the French
      Epidemiological Study on the Genetics and Environment of Asthma (EGEA) reported
      strong evidence of linkage of 11p14 to eczema. OBJECTIVE: Our purpose was to
      conduct fine-scale mapping of the 11p14 region to identify the genetic variants
      associated with eczema. METHODS: Association analyses were first conducted in the
      family sample from the French EGEA by using 2 methods: the family-based
      association method and logistic regression. Replication of the EGEA findings was
      sought in French Canadian and United Kingdom family samples, which, similarly to
      EGEA samples, were ascertained through asthma. We also tested for association in
      2 German samples ascertained through eczema. RESULTS: We found significant
      association of eczema with 11p14 genetic variants in the vicinity of the linkage
      peak in EGEA (P = 10(-4) for rs1050153 by using the family-based association
      method, which reached the multiple testing-corrected threshold of 10(-4); P =
      .003 with logistic regression). Pooled analysis of the 3 asthma-ascertained
      samples showed strong improvement in the evidence for association (P = 6 * 10(-6)
      for rs293974, P = 3 * 10(-5) for rs1050153, and P = 8 * 10(-5) for rs15783). No
      association was observed in the eczema-ascertained samples. CONCLUSION: The
      significant single nucleotide polymorphisms are located within the overlapping
      anoctamin 3 (ANO3) and mucin 15 (MUC15) genes. Several lines of evidence suggest
      that MUC15 is a strong candidate for eczema. Further investigation is needed to
      confirm our findings and to better understand the role of the ANO3/MUC15 locus in
      eczema and its relationship with respect to asthma.

PMID- 22657409
TI  - Outcomes of 100 consecutive open, baked-egg oral food challenges in the allergy
      office.

PMID- 22657410
TI  - Evaluation of a patient with hyper-IgM syndrome.

PMID- 22657529
TI  - Understanding and creating value from open source drug discovery for neglected
      tropical diseases.
AB  - INTRODUCTION: The health commons (known as open source) refers to knowledge-based
      assets that are shared or owned in common by stakeholders found across the health
      value chain. The unique challenges presented to drug discovery and development
      including biological, chemical and economic are particularly salient for
      neglected tropical diseases (NTDs), warranting new networks and models of open
      collaboration between scientists from the public and private sectors. AREAS
      COVERED: The goal of this paper is to progress beyond the review of open source
      strategies NTDs to a discussion of an assessment of these strategies. The authors
      discuss the notion of evolving openness across the pharmaceutical value chain and
      discuss and develop a framework for assessing the value and outcomes of open
      source drug discovery for NTDs, based on the available literature. EXPERT
      OPINION: Collectively, open source programs for NTDs, beyond the actual deposits
      themselves, should foster linkages between experts in key disease arenas,
      encourage collaborations through such linkages and most urgently enable human
      capacity development. Quantifying their value in absolute terms is not an easy
      task since exchange markets do not always exist for deposited and shared assets.
      From the perspective of capacity development, the potential and benefits
      certainly exist for program development involving NTD initiatives, institutions
      and students in disease-endemic countries. Here, stakeholders such as public
      grant agencies and private sector sponsors can play a role in encouraging
      initiatives that link open and broad knowledge dissemination to the development
      of local human and technological capacity in NTD-endemic countries.

PMID- 22657530
TI  - Isolation identification and biochemical characterization of a novel halo
      tolerant lipase from the metagenome of the marine sponge Haliclona simulans.
AB  - BACKGROUND: Lipases (EC 3.1.1.3) catalyze the hydrolysis of triacyl glycerol to
      glycerol and are involved in the synthesis of both short chain and long chain
      acylglycerols. They are widely used industrially in various applications, such as
      baking, laundry detergents and as biocatalysts in alternative energy strategies.
      Marine ecosystems are known to represent a large reservoir of biodiversity with
      respect to industrially useful enzymes. However the vast majority of
      microorganisms within these ecosystems are not readily culturable. Functional
      metagenomic based approaches provide a solution to this problem by facilitating
      the identification of novel enzymes such as the halo-tolerant lipase identified
      in this study from a marine sponge metagenome. RESULTS: A metagenomic library was
      constructed from the marine sponge Haliclona simulans in the pCC1fos vector,
      containing approximately 48,000 fosmid clones. High throughput plate screening on
      1% tributyrin agar resulted in the identification of 58 positive lipase clones.
      Following sequence analysis of the 10 most highly active fosmid clones the
      pCC1fos53E1 clone was found to contain a putative lipase gene lpc53E1, encoded by
      387 amino acids and with a predicted molecular mass of 41.87 kDa. Sequence
      analysis of the predicted amino acid sequence of Lpc53E1 revealed that it is a
      member of the group VIII family of lipases possessing the SXTK motif, related to
      type C beta-lactamases. Heterologous expression of lpc53E1 in E. coli and the
      subsequent biochemical characterization of the recombinant protein, showed an
      enzyme with the highest substrate specificity for long chain fatty acyl esters.
      Optimal activity was observed with p- nitrophenyl palmitate (C16) at 40 degrees
      C, in the presence of 5 M NaCl at pH 7; while in addition the recombinant enzyme
      displayed activity across broad pH (3-12) and temperature (4 -60 degrees C)
      ranges and high levels of stability in the presence of various solvents at NaCl
      concentrations as high as 5 M and at temperatures ranging from 10 to 80 degrees
      C. A maximum lipase activity of 2,700 U/mg was observed with 10 mM p-nitrophenyl
      palmitate as substrate, in the presence of 5 mM Ca2+ and 5 M NaCl, and a reaction
      time of 15 min at pH 7 and 40 degrees C; while KM and Vmax values were calculated
      to be 1.093 mM-1 and 50 MUmol/min, respectively. CONCLUSION: We have isolated a
      novel halo tolerant lipase following a functional screen of a marine sponge
      fosmid metagenomic library. The activity and stability profile of the recombinant
      enzyme over a wide range of salinity, pH and temperature; and in the presence of
      organic solvent and metal ions suggests a utility for this enzyme in a variety of
      industrial applications.

PMID- 22657531
TI  - Clostridium difficile and Entamoeba histolytica infections in patients with
      colitis in the Philippines.
AB  - Amoebiasis is a common cause of non-specific colitis in the Philippines. The
      prevalence of Clostridium difficile infection with colitis is unknown. Empiric
      use of metronidazole for colitis treatment is widely practiced. We investigated
      the association of C. difficile or Entamoeba histolytica infection with
      endoscopically/histopathologically proven colitis among adults in the
      Philippines. Two hundred and ten patients undergoing colonoscopy were enrolled.
      Demographic and clinical data were reviewed. Stool specimens were assayed for C.
      difficile and E. histolytica by ELISA. Microscopy was performed. The mean age of
      the patients was 53 y (range: 19-88 y) and 53% were male. Colitis was diagnosed
      in 39 of 205 patients. Clostridium difficile, E. histolytica and parasites were
      seen in 17 (43.6%), 10 (25.6%) and 11 (28.2%), respectively, of patients with
      colitis compared with 36 (21.7%; p=0.005), 13 (7.8%; p=0.001) and 56 (33.7%;
      p=0.51), respectively, of those without colitis. Diarrhoea and antibiotic intake
      history were significantly more common among patients with colitis than those
      without (43.6% and 20.5% vs 18.1% and 5.4%; p=0.001 and p=0.006, respectively).
      The mean duration of diarrhoea was 2.53 d shorter among patients with colitis.
      The most frequent antibiotics taken were fluoroquinolones and metronidazole (50%
      and 40% of antibiotic courses, respectively, in patients with colitis). This
      study suggests that C. difficile infection is common and might be overlooked in
      settings where amoebiasis and intestinal parasitism are endemic.

PMID- 22657532
TI  - Western blot analysis as an aid for the diagnosis of cutaneous leishmaniasis due
      to Leishmania major.
AB  - Cutaneous leishmaniasis (CL) due to Leishmania major is endemic in the Old World.
      To evaluate the diagnostic value of Western blot (WB) compared with IFAT, we
      tested serum samples from 45 patients with proven CL. Twenty-one (47%) patients
      were positive by IFAT and all patients were positive by WB with specific bands
      against 14kDa and/or 18kDa Leishmania antigens. Our results suggest that WB could
      be a useful non-invasive tool for the diagnosis of CL caused by L. major.

PMID- 22657533
TI  - Efficacy of praziquantel syrup versus crushed praziquantel tablets in the
      treatment of intestinal schistosomiasis in Ugandan preschool children, with
      observation on compliance and safety.
AB  - Preschool children (aged <=5 years) have so far been overlooked by mass treatment
      campaigns targeting schistosomiasis, even though praziquantel (PZQ) has been
      shown to be well tolerated and effective within this age group. The WHO provided
      the Ugandan Ministry of Health with a syrup formulation of PZQ with the aim of
      assessing its safety and efficacy in comparison with crushed PZQ tablets for the
      treatment of intestinal schistosomiasis in preschool children. This study
      included 1144 preschool children randomly assigned to two treatment arms (PZQ
      syrup or crushed PZQ tablet) regardless of infection status for direct
      comparison. Diagnosis of intestinal schistosomiasis was assessed using single
      stool sample, double Kato-Katz smear examinations. Parasitological cure was
      assessed 3 weeks after treatment. The observed cure rate was 80.9% for the PZQ
      syrup arm and 81.7% for the crushed PZQ tablet arm, with egg reduction rates of
      86.1% and 89.0%, respectively. Pre-treatment infection intensity was observed to
      influence cure rates significantly, with cure rates of 88.6% for light
      infections, 74.5% for moderate infections and 67.4% for heavy infections. No
      significant difference was found in non-compliance between the PZQ syrup (11.1%)
      and crushed PZQ tablet (14.7%) arms. PZQ syrup and crushed PZQ tablets have very
      similar efficacies in the treatment of intestinal schistosomiasis in preschool
      children.

PMID- 22657534
TI  - Implications for health education and intervention strategies arising from
      children's caregivers concerns following successful malaria control.
AB  - Malaria is still responsible for 10% of the total disease burden in Africa. This
      study was an empirical investigation addressing the extent to which, and the ways
      in which, sociocultural, family-based, demographic and economic circumstances in
      a poor rural African environment influence levels of active malaria infection
      risk awareness. Face-to-face interviews were conducted and the questions included
      both open-ended questions allowing for unprompted replies and closed fixed-answer
      alternative (prompted) items. The adult female responsible for the day-to-day
      care of the children in 156 homesteads (60 in each of two malaria villages and 36
      in a reference village) was interviewed. The families received financial
      assistance but little physical support from the fathers. Unemployment, poverty,
      crime and clean water were perceived as the main, unprompted threats, and
      everyday awareness appeared to exclude the potentially serious disease threats of
      malaria. Only when malaria was prompted did the concerns rise to 52% and 38% in
      the sprayed villages. The apparent discrepancy between actual daily and potential
      future threats significantly increases the difficulty of mobilising communities
      for preventive action regarding potential threats. The lack of community
      involvement in an existing community-passive malaria control system may become a
      problem when promoting new/additional measures to reduce exposure to indoor
      residual spraying chemicals.

PMID- 22657535
TI  - Factors associated with rotavirus diarrhoea in children living in a socially
      diverse urban centre in Brazil.
AB  - A case-control study, aimed at identifying factors associated with rotavirus
      diarrhoea cases presenting to health facilities, was conducted in children from
      low-income and middle-low-income families in Brazil. Cases were 390 children with
      diarrhoea and rotavirus in stools; controls were 1674 children without diarrhoea
      presenting to the same facilities. Data were collected by questionnaire and
      observations during home visits. Explanatory variables were grouped according to
      a conceptual model of causation. The ORs by non-conditional logistic regression
      and population-attributable fractions were calculated. Socioeconomic factors
      contributed a third of cases, followed by contact with diarrhoea cases and by not
      being breast fed. In cases aged <1 year, not being breast fed was the main
      determinant, followed by socioeconomic factors, and crowding and contact outside
      the home; in older children, socioeconomic factors followed by contact inside and
      outside the home were the main determinants. Environmental and sanitation
      variables were not associated with diarrhoea in the final model, and
      socioeconomic factors were only partly mediated by proximal variables.
      Transmission of rotavirus appears to be mostly by person-to-person contact, and
      shows marked social differentials not explained by the biological factors
      studied. The rotavirus vaccine is unlikely to protect against the full range of
      circulating genotypes of rotavirus, and understanding rotavirus epidemiology
      remains essential to the development of control policies.

PMID- 22657536
TI  - High initial default in patients with smear-positive pulmonary tuberculosis at a
      regional hospital in Accra, Ghana.
AB  - Sputum smear-positive TB patients, diagnosed in the laboratory, who never start
      anti-TB treatment are classified as 'initial defaulters'. In Ridge Hospital,
      Accra, Ghana, there were 84 laboratory confirmed TB cases in 2009, of whom 32
      (38%) were initial defaulters. Cure and default rates based on this cohort were
      54% and 43% respectively, compared with rates of 87% and 8% when using the cohort
      based on 52 patients registered for treatment. This study highlights the problem
      of initial defaulters, and shows that programme performance may be poor when
      patients in laboratory registers are used as the cohort to evaluate treatment
      outcomes.

PMID- 22657537
TI  - Structural insights into the redox-regulated dynamic conformations of human
      protein disulfide isomerase.
AB  - AIM: Human protein disulfide isomerase (hPDI) is a key enzyme and a redox
      regulated chaperone responsible for oxidative protein folding in the endoplasmic
      reticulum. This work aims to reveal the molecular mechanism underlying the redox
      regulated functions of hPDI by determining the crystal structures of hPDI in
      different redox states. RESULTS: The structures of hPDI (abb'xa') in both the
      reduced and oxidized states showed that the four thioredoxin domains of a, b, b',
      and a' are arranged as a horseshoe shape with two CGHC active sites,
      respectively, in domains a and a' facing each other at the two ends. In reduced
      hPDI, domains a, b, and b' line up in the same plane, whereas domain a' twists
      ~45 degrees  out. The two active sites are 27.6 A apart. In oxidized hPDI, the
      four domains are differently organized to stay in the same plane, and the
      distance between the active sites increases to 40.3 A. In contrast to the closed
      conformation of reduced hPDI, oxidized hPDI exists in an open state with more
      exposed hydrophobic areas and a larger cleft with potential for substrate
      binding. INNOVATION: This is the first report of the high-resolution structures
      of hPDI containing all four domains in both the reduced and the oxidized states.
      It reveals the redox-regulated structural dynamic properties of the protein.
      CONCLUSION: The redox-regulated open/closed conformational switch of hPDI endows
      the protein with versatile target-binding capacities for its enzymatic and
      chaperone functions.

PMID- 22657539
TI  - professional consulting services directory.

PMID- 22657540
TI  - Radiometer copenhagen.

PMID- 22657538
TI  - A key regulator of cholesterol homoeostasis, SREBP-2, can be targeted in prostate
      cancer cells with natural products.
AB  - There is growing evidence showing that prostate cancer cells have perturbed
      cholesterol homoeostasis, accumulating cholesterol to promote cell growth.
      Consequently, cholesterol-lowering drugs such as statins are being evaluated in
      prostate cancer treatment. Furthermore, natural products such as betulin (from
      birch tree bark) and tocotrienol (a minor form of vitamin E) have been shown to
      lower cholesterol levels. Using these drugs and oxysterols, we have determined
      which aspects of cholesterol homoeostasis should be targeted in prostate cancer,
      e.g. cellular cholesterol levels are increased by the transcription factor SREBP
      2 (sterol-regulatory-element-binding protein isoform 2), whereas LXR (liver X
      receptor) promotes cholesterol efflux. Whereas betulin exerted non-specific
      effects on cell viability, tocotrienols produced a strong direct correlation
      between SREBP-2 activity and cell viability. Mechanistically, tocotrienols
      lowered SREBP-2 activity by degrading mature SREBP-2 independently of the
      proteasome. In contrast, no correlation was seen between LXR activity and cell
      viability, implying that SREBP-2 is a better target than LXR for prostate cancer
      treatment. Lastly, androgen-dependent and -independent LNCaP cells were both
      sensitive to tocotrienols. Overall, this suggests that tocotrienols and other
      drugs targeting the SREBP-2 pathway are a potential therapeutic option for
      prostate cancer.

PMID- 22657541
TI  - Water industry research on upswing.

PMID- 22657542
TI  - Martek instruments, inc.

PMID- 22657543
TI  - States.

PMID- 22657544
TI  - Washington.

PMID- 22657545
TI  - Scholarship.

PMID- 22657546
TI  - Science.

PMID- 22657547
TI  - Technology.

PMID- 22657548
TI  - Business.

PMID- 22657549
TI  - Analysis of polychlorinated dioxins and furans.

PMID- 22657550
TI  - Highlights of EPA's 1984 Regulatory Agenda.

PMID- 22657551
TI  - Wiley-interscience.

PMID- 22657552
TI  - What's Happening in Chemistry?

PMID- 22657553
TI  - Polynuclear aromatic hydrocarbons.

PMID- 22657554
TI  - Upcoming environmental program.

PMID- 22657555
TI  - Normandeau associates, inc.

PMID- 22657557
TI  - National association of environmental professionals.

PMID- 22657556
TI  - Products.

PMID- 22657559
TI  - Classified section.

PMID- 22657558
TI  - Literature.

PMID- 22657561
TI  - Regioselective synthesis of cellulose ester homopolymers.
AB  - Regioselective synthesis of cellulose esters is extremely difficult due to the
      small reactivity differences between cellulose hydroxyl groups, small differences
      in steric demand between acyl moieties of interest, and the difficulty of
      attaching and detaching many protecting groups in the presence of cellulose ester
      moieties without removing the ester groups. Yet the synthesis of homopolymers of
      particular regioselectively substituted anhydroglucose esters is of critical
      importance to allow us to determine the analytical characteristics of such
      homopolymers, their structure-property relationships, and to obtain guidance that
      may ultimately enable identification and synthesis of cellulose derivatives with
      superior properties for various applications. We report here a new, general
      synthesis of both cellulose-2,6-O-diesters and cellulose-2,6-A-O-3-B-O-triesters
      with a high degree of regioselectivity, employing 3-O-allylcellulose as a key
      protected precursor. 3-O-Allylcellulose was identified as a protected
      intermediate with high potential for the synthesis of these derivatives with the
      aid of molecular modeling of corresponding glucose analogs. We report also the
      first analytical and structure property studies of these regioselectively
      substituted cellulose esters.

PMID- 22657562
TI  - Medical radiation safety: rational policy, irrational science.

PMID- 22657563
TI  - Thyroid gland cutaneous fistula secondary to a migratory fish bone: a case
      report.
AB  - INTRODUCTION: We report an extremely rare case of a migratory fish bone
      penetrating through the thyroid gland. CASE PRESENTATION: A 56-year-old Japanese
      woman presented with a two-month history of a painless cutaneous fistula in her
      anterior neck with pus discharge. Endoscopic examinations showed no abnormality,
      but computed tomography revealed a bone-density needle-shaped foreign body
      sticking out anteroinferior from the esophagus wall, penetrating through her left
      thyroid lobe and extending nearly to the anterior cervical skin. A migratory fish
      bone was suspected, and the foreign body was removed under general anesthetic,
      combined with a hemithyroidectomy. The injured esophageal mucosa was sutured and
      closed. Our patient's postoperative course was uneventful, and she was allowed
      oral food intake seven days after the surgery. No evidence of recurrence was seen
      over the postoperative follow-up period of 42 weeks. CONCLUSION: We should be
      aware that fish bone foreign bodies may migrate out of the upper digestive tract
      and lodge in the thyroid gland.

PMID- 22657564
TI  - Risk factors for cytomegalovirus retinitis in patients with cytomegalovirus
      viremia after hematopoietic stem cell transplantation.
AB  - PURPOSE: To evaluate the risk factors for cytomegalovirus (CMV) retinitis in
      patients with CMV viremia after hematopoietic stem cell transplantation (HSCT).
      DESIGN: Retrospective cohort study. PARTICIPANTS: We included all patients with
      CMV viremia detected by polymerase chain reaction after HSCT between April 2009
      and August 2011. Risk factors for CMV retinitis were evaluated in the cohort of
      270 patients with CMV viremia, who survived >= 12 weeks after HSCT and were
      screened for CMV retinitis. METHODS: Retrospective review of clinical records and
      laboratory results. MAIN OUTCOME MEASURES: Survival analysis of patients in the
      cohort and frequency of CMV retinitis in relation to various factors. Variables
      analyzed were demographics, human leukocyte antigen (HLA) matched versus
      mismatched, related versus unrelated donor, preconditioning regimens, delayed
      engraftment of lymphocyte, presence of acute or chronic graft-versus-host
      disease, highest CMV DNA level in blood (copies/ml), cumulative period of CMV
      viremia (weeks), and CMV infection verified by culture or immunohistology in
      bronchoalveolar lavage or visceral biopsy specimens. RESULTS: Of the 708 patients
      who underwent HSCT during the study period, 363 (51%) developed CMV viremia after
      HSCT. Of the 363 patients with CMV viremia, 270 underwent retinal examination for
      CMV retinitis. We detected CMV retinitis in 15 of 270 patients with CMV viremia.
      In the univariate analysis, HLA-mismatched HSCT, HSCT from an unrelated donor,
      engraftment day, peak CMV DNA level, and duration of viremia were associated with
      the development of CMV retinitis. In the adjusted multivariate analysis, only
      peak CMV DNA blood levels predicted the development of CMV retinitis (hazard
      ratio, 25.0; 95% confidence interval, 3.0-210.8). An additional validity analysis
      by receiver operating characteristic area under curve suggested that a cutoff of
      7.64 * 10(4) copies/mL best predicted the development of CMV retinitis by CMV DNA
      levels in blood. CONCLUSIONS: The development of CMV retinitis should be
      carefully monitored in patients with a significant viral load, which is
      represented by a peak CMV DNA level >7.64 * 10(4) copies/ml and a long duration
      of CMV viremia, especially when patients received HSCT from an unrelated or HLA
      mismatched donor and showed delayed lymphocyte engraftment.

PMID- 22657565
TI  - Supported lipid monolayer with improved nanomechanical stability: effect of
      polymerization.
AB  - We study the effect of polymerization on the nanomechanical stability of
      supported lipid monolayers consisting of 1,2-di-(10Z,12Z-tricosadiynoyl)-sn
      glycero-3-phosphocholine by means of force mapping using an atomic force
      microscope. For both nonpolymerized and polymerized lipid monolayers, we
      investigate the break-through forces required to rupture the monolayers for a
      whole range of loading velocities. We show that the average break-through force
      exerted by the tip and required to penetrate the monolayer has a logarithmic
      dependence on the loading rate. Both Young moduli and intrinsic Gibbs energies
      have been determined for the nonpolymerized and polymerized lipid monolayers, and
      we show a drastic effect of polymerization on the nanomechanical stability of the
      monolayer with an increase by a factor of ~100 for the young modulus and ~3 for
      the intrinsic Gibbs activation energy.

PMID- 22657566
TI  - Association between ghrelin levels and BMD: a cross sectional trial.
AB  - OBJECTIVE: Our aim was to determine whether the level of plasma total ghrelin
      varies with the menopause stage (pre-, peri-, and postmenopause). PARTICIPANTS
      AND INTERVENTIONS: Women were divided in three groups: premenopausal,
      perimenopausal and postmenopausal. All participants had bone mineral densitometry
      and blood assay of plasma ghrelin, estradiol E2. Correlation between plasma
      ghrelin levels, their reproductive status and BMD was done. RESULTS: The mean
      plasma level of ghrelin was significantly decreased in the perimenopausal and
      postmenopausal groups in comparison to the premenopausal group. A significant
      positive correlation was found between ghrelin and each of E2 and BMD (at one or
      more of the three sites assessed) in all subjects, as well as, in peri- and
      postmenopausal women, whereas a significant negative correlation was found
      between ghrelin and FSH. CONCLUSION: It may be assumed that ghrelin can affect
      BMD. Whether ghrelin and estrogen work independent or through convergent
      mechanisms needs further studies.

PMID- 22657567
TI  - [Nutritional support in patients with liver cirrhosis].
AB  - Given the liver's multiple synthetic, regulatory and detoxifying functions, one
      of the characteristics accompanying severe hepatocellular dysfunction is the
      presence of malnutrition. This disorder is highly frequent in liver cirrhosis,
      even in the relatively early stages of the disease. Independently of the cause of
      the cirrhosis, poor nutritional status is associated with a worse prognosis and
      therefore early intervention to correct nutrient deficiency can prolong life
      expectancy, improve quality of life, reduce complications and increase the
      probability of successful transplantation. The present article reviews current
      knowledge of the diagnosis and management of malnutrition in patients with
      cirrhosis. Special attention is paid to the concept of the late evening snack and
      its characteristics, composition and probable benefits in the course of the
      disease.

PMID- 22657568
TI  - [An Asian man with recurrent abdominal pain].
AB  - Recurrent pyogenic cholangitis (RPC), or oriental cholangiohepatitis, is
      characterized by intrabiliary pigment stone formation, whose main manifestation
      consists of recurrent episodes of cholangitis, although other biliopancreatic
      complications can also occur. RPC develops mainly in Asian patients, in whom this
      entity is one of the main causes of acute abdominal pain. The differential
      diagnosis should be established with all other entities associated with
      intrahepatic stone formation, which is more common in Asian countries compared
      with the predominance of gallstone formation in the West. The diagnostic and
      therapeutic approach requires collaboration among gastroenterologists,
      radiologists and gastrointestinal surgeons. We review the most important
      clinical, diagnostic and therapeutic features of this entity, which, although
      clearly predominant in Asia, is increasingly diagnosed in our setting.

PMID- 22657569
TI  - Nonvariceal upper gastrointestinal bleeding in Portugal: a multicentric
      retrospective study in twelve Portuguese hospitals.
AB  - BACKGROUND: Nonvariceal upper gastrointestinal bleeding (NVUGIB) is associated
      with important mortality. More information is needed in order to improve NVUGIB
      management. The aims of this study were: (a) characterizing Portuguese patients
      and clinical approaches used in NVUGIB, (b) comparing management used in Portugal
      with management globally used in European countries, (c) identify factors
      associated with management options, and (d) identify factors associated with
      adverse outcome. METHODS: ENERGiB was an observational, retrospective cohort
      study, on NVUGIB with endoscopic evaluation, carried across Europe. This study
      focuses on Portuguese patients of the ENERGiB study. Patients were managed
      according to routine care. Later, data were collected from files.
      Multivariate/univariate analyses were conducted on predictive factors of poor
      outcome and clinical decisions. RESULTS: Patients (n=404) were mostly men
      (66.8%), mean age 68, with co-morbidities (72%), frequently on NSAIDs/aspirin.
      Most were assisted by general medical (57.8%) or surgical team (20.6%), only
      19.4% by gastroenterology/GI-bleeding team. PPI was largely used.
      Gastric/duodenal ulcers, erosive gastritis and esophagitis were the main bleeding
      causes. 10% had bleeding persistence/recurrence. Death occurred in 24 patients,
      20 from a non-bleeding related cause. Poor outcomes were related with age >65, co
      morbidities, fresh blood haematemesis, shock/syncope, bleeding through previous
      nasogastric tube, massive fluid replacement or transfusions besides erythrocytes.
      CONCLUSIONS: This study contributed to characterization of Portuguese patients
      and NVUGIB episodes in real clinical setting and identified factors associated
      with a poor outcome. It also identified differences, especially in the
      organization of GI bleeding teams, which might help us to improve the management
      of these patients.

PMID- 22657570
TI  - [Early liver transplantation in alcoholic hepatitis: an option in the treatment
      of steroid-unresponsive patients].

PMID- 22657572
TI  - The OTSC(r) Proctology clip system for anorectal fistula closure: the 'anal
      fistula claw': case report.
AB  - Abstract   Surgical treatment of high or complex anal fistulas often renders
      unsatisfying results. This is the report of the first successful closure of such
      anal fistula using a special Nitinol clip and applicator, the OTSC(r) Proctology
      system (Ovesco AG, Tuebingen, Germany): A 54-year old female patient was
      suffering from a high transsphincteric anal fistula. After seton drainage of the
      fistula for ten weeks, the fistula track was debrided using a special fistula
      brush. After transanal clip release from the applicator, the internal fistula
      opening was adequately closed by the clip. Eight months after clip closure the
      fistula had healed and the clip was removed using the OTSC(r) Proctology Clip
      Cutter. Fistula closure using the OTSC(r) Proctology system represents a
      promising sphincter-preserving minimally invasive procedure.

PMID- 22657571
TI  - A phenomenological model of seizure initiation suggests network structure may
      explain seizure frequency in idiopathic generalised epilepsy.
AB  - We describe a phenomenological model of seizure initiation, consisting of a
      bistable switch between stable fixed point and stable limit-cycle attractors. We
      determine a quasi-analytic formula for the exit time problem for our model in the
      presence of noise. This formula--which we equate to seizure frequency--is then
      validated numerically, before we extend our study to explore the combined effects
      of noise and network structure on escape times. Here, we observe that weakly
      connected networks of 2, 3 and 4 nodes with equivalent first transitive
      components all have the same asymptotic escape times. We finally extend this work
      to larger networks, inferred from electroencephalographic recordings from 35
      patients with idiopathic generalised epilepsies and 40 controls. Here, we find
      that network structure in patients correlates with smaller escape times relative
      to network structures from controls. These initial findings are suggestive that
      network structure may play an important role in seizure initiation and seizure
      frequency.

PMID- 22657573
TI  - A quantitative scale to define endoscopic torque control during natural orifice
      surgery.
AB  - INTRODUCTION: The drive to perform procedures with the least impact on the
      patient has meant that interest in natural orifice translumenal endoscopic
      surgery (NOTES) continues to proliferate. However, endoscope control within the
      extralumenal environment remains a significant challenge. This study aims to
      define a method to quantitatively assess endoscopic torque control as an
      indication of performance. MATERIAL AND METHODS: Fourteen endoscopists performed
      a ten-target navigational task within a simulated NOTES environment whilst wrist
      movements were tracked with an optical motion tracker. Patterns of wrist
      movements were translated to a binary form enabling differentiation of the
      specified movement from no movement. Three patterns were discernable suggesting
      the discrimination of purposeful over random manipulations. Three independent
      assessors scored 140 patterns on a scale of 1 to 3 determined by which pattern
      was the most appropriate fit. RESULTS: Mean score for novices was 16 (+/- 3) and
      for clinicians 22 (+/- 7). Inter-rater reliability (kappa statistic function)
      between the assessors ranged from 0.637 to 0.751 p < 0.001 referred to as a
      substantial assessment tool. The internal consistency between all variables using
      Chronbach's alpha function was 0.948 (p < 0.001). CONCLUSIONS: Pattern of
      movements extrapolated from the wrist can be used as a method of measuring
      endoscope torque control during a translumenal navigation task.

PMID- 22657574
TI  - Automated recycling of chemistry for virtual screening and library design.
AB  - An early stage drug discovery project needs to identify a number of chemically
      diverse and attractive compounds. These hit compounds are typically found through
      high-throughput screening campaigns. The diversity of the chemical libraries used
      in screening is therefore important. In this study, we describe a virtual high
      throughput screening system called Virtual Library. The system automatically
      "recycles" validated synthetic protocols and available starting materials to
      generate a large number of virtual compound libraries, and allows for fast
      searches in the generated libraries using a 2D fingerprint based screening
      method. Virtual Library links the returned virtual hit compounds back to
      experimental protocols to quickly assess the synthetic accessibility of the hits.
      The system can be used as an idea generator for library design to enrich the
      screening collection and to explore the structure-activity landscape around a
      specific active compound. 

PMID- 22657575
TI  - The application of human tissue for drug discovery and development.
AB  - Human tissues are invaluable resources for pharmaceutical research. They provide
      information about disease pathophysiology--and equally importantly, healthy
      function; confirmation (or refutation) of potential drug targets; validation (or
      otherwise) of other models employed; and functional models for assessing drugs'
      effects, whether beneficial or undesirable, in the most appropriate environment
      that can be replicated outside the human body. While human tissues have long been
      prized by pathologists in furthering our understanding of disease processes,
      there is a growing appreciation of their value at the late pre-clinical stage of
      drug discovery. Human tissues' potential to contribute to earlier phases of the
      process, before significant resources have been expended, is also now gaining
      recognition. Mounting concern over high rates of clinical stage drug failures
      mandates exploration of avenues for improving efficiency. Human tissue-based
      assays could play a key role in improving the translation process, as well as in
      moving towards stratified or personalised medicines. This editorial highlights
      some of the potential benefits of introducing human biosamples at each stage of
      the research process as a drug moves from concept to clinic. Some of the
      challenges with respect to obtaining tissues, minimising variability and gaining
      acceptance are also discussed.

PMID- 22657576
TI  - Cortisol treatment reduces ghrelin signaling and food intake in tilapia,
      Oreochromis mossambicus.
AB  - It is well known that after a stressor, levels of plasma cortisol rise, inducing
      physiological changes within the animal that are directed toward maintaining
      homeostasis. Less well understood is the role of cortisol in regulating food
      intake in teleosts. This study investigated the effect of cortisol on food intake
      and regulation of the neuroendocrine appetite-stimulating hormones, neuropeptide
      Y (NPY) and ghrelin, in tilapia (Oreochromis mossambicus). Male and female
      tilapia were randomly assigned to one of the following treatments: unhandled
      control, vehicle-injected control, or cortisol (2 MUg/g BW). Food intake was
      determined 24 h after injection during a 1-h feeding trial. Cortisol reduced food
      intake (P<0.001). An identical study was conducted to measure the effects of 24-h
      cortisol treatment on the endocrine regulators of food intake. Cortisol reduced
      stomach expression of ghrelin mRNA (P<0.05) and plasma concentrations of ghrelin
      (P<0.05). In the hypothalamus/optic tectum cortisol reduced levels of GHSR1a-LR
      (biologically active ghrelin receptor) mRNA. In the telencephalon/preoptic area
      cortisol significantly reduced levels of NPY and GHSR1b-LR (biologically inactive
      ghrelin receptor) mRNA. These findings suggest that anorexigenic actions of
      cortisol may be mediated via two separate pathways: (1) reducing circulating
      ghrelin levels as well as GHSR1a-LR expression in the hypothalamus/optic tectum
      and/or (2) suppressing NPY expression in the telencephalon/preoptic area.

PMID- 22657577
TI  - [The new strategies for disease mongering].

PMID- 22657578
TI  - [Risk of hemorrhage in patients older than 85 years, anticoagulated due to atrial
      fibrillation].
AB  - BACKGROUND: Atrial fibrillation is the most common cardiac tachyarrhythmia and is
      an important independent risk factor for ischemic stroke. Its prevalence begins
      to increase in both sexes after 40 years of age as well as the risk of
      hemorrhage. The aim of this study was to compare the annual rate of hemorrhagic
      events between patients older and younger than 85 years, with diagnosis of
      nonvalvular atrial fibrillation and anticoagulated with warfarin. MATERIAL AND
      METHODS: A retrospective study was performed. We included 118 patients with
      diagnosis of nonvalvular atrial fibrillation monitorized by an informatized
      follow up system. RESULTS: The study follow-up was 28,2 +/- 17,5 months and 24
      patients (20,3%) were older than 85 years of age. The rate of major bleedings was
      4,62%/year (older than 85 years) vs 0,95%/year (younger than 85 years) , p= 0,05,
      OR 6,57 (IC 95% 1,04-41,8) and minor bleeding was 4,62%/year (older than 85
      years) vs 5,2%/year (younger than 85 years), p=0,99, OR 1,08 (IC 95% 0,28-4,21).
      There was no difference in the Time in Therapeutic Range between both groups
      (56.4 +/- 16.3 % vs 60.5 +/- 17.7 %, p 0,30). CONCLUSION: The age should not be
      considered a contraindication to anticoagulant therapy, however, special care and
      careful monitoring of patients older than 85 years should be considered due to
      they had high risk of bleeding.

PMID- 22657579
TI  - [Chemical ablation of the gallbladder with sodium hypochlorite in an animal
      model].
AB  - INTRODUCTION: The cholecystectomy is the current treatment of the biliary
      lithiasis. Nevertheless there have been attempts in order to eliminate the
      gallbladder epithelium and to generate the sclerosis of the organ using chemical
      substances, heat and laser. OBJECTIVE: Sodium hypochlorite and fibrin glue is
      proposed to achieve the ablation of the gallbladder mucosa and sclerosis.
      MATERIALS AND METHODS: Thirty rabbits were divided into three groups of 10.
      Accessing surgically to the gallbladder, sodium hypochlorite was injected,
      afterward the same was done with fibrin glue to occlude the cystic duct and
      collapse the organ lumen, avoiding the bile reflux. In the control groups ethanol
      plus fibrin adhesive and physiological solution was used. In day 65 the animals
      were sacrificed and the result of the procedure was observed macroscopic and
      histologically. RESULTS: Eight of the gallbladders treated with sodium
      hypochlorite disappeared leaving a small subhepatic scar. There were no intra nor
      postoperative complications. In the group of the ethanol the result was
      successful only in one case, and with saline solution there was no ablation. A
      significant difference exists for the group treated with sodium hypochlorite plus
      fibrin glue compared to the ethanol plus fibrin adhesive group (p <0,0055) and
      the saline solution group (p <0,0007). CONCLUSION: In this experimental model
      there was possible the ablation of the gallbladder using sodium hypochlorite as
      sclerosing agent and fibrin glue to collapse the lumen and to occlude the cystic
      duct.

PMID- 22657580
TI  - [Alcoholism: a practical approach].

PMID- 22657581
TI  - [Hepatic hematoma in HELLP  syndrome].
AB  - OBJECTIVE: The purpose of this study was to review our experience with patients
      having hepatic rupture or hematoma caused by HELLP syndrome. MATERIALS AND
      METHODS: Descriptive simple cross sectional retrospective study. A review was
      performed of medical records of all patients admitted at our Hospital's intensive
      care unit having HELLP syndrome during pregnancy or puerperium between February
      1999 and February 2010. Patients complicated with hematoma or hepatic rupture
      were included. RESULTS: Three cases were identified. The average maternal age was
      35 years old and the average gestational age at delivery was 33 weeks. The most
      frequent signs and symptoms were sudden onset of abdominal pain and shock. A
      distinctive laboratory finding was anemia. Surgical treatment was omental
      patching in one of the patients and it was conservative with drainages in the
      other two cases. Maternal and perinatal mortality were 33 %. CONCLUSION: Based on
      our experience and the literature review, we can conclude that hepatic hematoma
      and rupture associated with HELLP syndrome represent a life-threatening
      complication in which early detection is very important to achieve a proper
      diagnosis and treatment. Patients should be treated by a multidisciplinary team
      in reference centers being carefully followed with adequate hemodynamic support
      and regular images to improve the survival maternal rate.

PMID- 22657582
TI  - [Complicated urethral diverticulum].

PMID- 22657583
TI  - Ultrasound guided lateral femoral cutaneous nerve (LFCN) block: safe and simple
      anesthesia for harvesting skin grafts.
AB  - Many burn patients experience more intense pain from the split thickness skin
      donor site than in the grafted burn wound in their postoperative period. Often,
      split thickness autografts are harvested from the lateral thigh area, which is
      innervated by the lateral femoral cutaneous nerve (LFCN). Sonographic nerve
      localization has been an increasingly popular technique to provide regional nerve
      blocks and we explore its role in improving pain control during skin harvesting.
      The LFCN was identified and blocked using ultrasound in 16 patients with a
      variety of wounds. The donor site was tested and marked after the injection.
      General anesthesia or sedation was administered after markings were completed. A
      postoperative survey was performed to assess the return of sensation at the donor
      site. All blocks were successful with adequate visualization of LFCN using
      ultrasound. Full anesthesia at the donor site, defined as absence of pain in
      response to a sharp object prick, was tested at 15 min and confirmed at 20 min
      after the block. The size of the anesthetized field ranged from 119 to 630 cm(2),
      with a mean surface area of 268.5 cm(2). Donor site sensation returned within 5
      16 h with a mean time of 9.1h. Ultrasound guided LFCN block provides a simple and
      safe choice of anesthesia for harvesting skin from the lateral thigh.

PMID- 22657584
TI  - Letter regarding "Treatment outcomes for keloid scar management in the pediatric
      burn population".

PMID- 22657585
TI  - Comments on "a system for 3D representation of burns and calculation of burnt
      skin area".

PMID- 22657586
TI  - Micronutrient deficiency in obese subjects undergoing low calorie diet.
AB  - BACKGROUND: The prevalence of micronutrient deficiencies is higher in obese
      individuals compared to normal-weight people, probably because of inadequate
      eating habits but also due to increased demands among overweight persons, which
      are underestimated by dietary reference intakes (DRI) intended for the general
      population. We therefore evaluated the dietary micronutrient intake in obese
      individuals compared to a reference population and DRI recommendations.
      Furthermore, we determined the micronutrient status in obese subjects undergoing
      a standardized DRI-covering low-calorie formula diet to analyze if the DRI meet
      the micronutrient requirements of obese individuals. METHODS: In 104 subjects
      baseline micronutrient intake was determined by dietary record collection. A
      randomly assigned subgroup of subjects (n = 32) underwent a standardized DRI
      covering low-calorie formula diet over a period of three months. Pre- and post
      interventional intracellular micronutrient status in buccal mucosa cells (BMC)
      was analyzed, as well as additional micronutrient serum concentrations in 14 of
      the subjects. RESULTS: Prior to dietetic intervention, nutrition was calorie-rich
      and micronutrient-poor. Baseline deficiencies in serum concentrations were
      observed for 25-hydroxyvitamin-D, vitamin C, selenium, iron, as well as beta
      carotene, vitamin C, and lycopene in BMC. After a three-month period of formula
      diet even more subjects had reduced micronutrient levels of vitamin C (serum,
      BMC), zinc, and lycopene. There was a significant negative correlation between
      lipophilic serum vitamin concentrations and body fat, as well as between iron and
      C-reactive protein. CONCLUSIONS: The present pilot study shows that micronutrient
      deficiency occurring in obese individuals is not corrected by protein-rich
      formula diet containing vitamins and minerals according to DRI. In contrast,
      micronutrient levels remain low or become even lower, which might be explained by
      insufficient intake, increased demand and unbalanced dispersal of lipophilic
      compounds in the body. TRIAL REGISTRATION: The study was registered at
      ClinicalTrials.gov (NCT01344525). The study protocol comprises only a part of the
      approved trial protocol.

PMID- 22657695
TI  - Mean-field description and propagation of chaos in networks of Hodgkin-Huxley and
      FitzHugh-Nagumo neurons.
AB  - We derive the mean-field equations arising as the limit of a network of
      interacting spiking neurons, as the number of neurons goes to infinity. The
      neurons belong to a fixed number of populations and are represented either by the
      Hodgkin-Huxley model or by one of its simplified version, the FitzHugh-Nagumo
      model. The synapses between neurons are either electrical or chemical. The
      network is assumed to be fully connected. The maximum conductances vary randomly.
      Under the condition that all neurons' initial conditions are drawn independently
      from the same law that depends only on the population they belong to, we prove
      that a propagation of chaos phenomenon takes place, namely that in the mean-field
      limit, any finite number of neurons become independent and, within each
      population, have the same probability distribution. This probability distribution
      is a solution of a set of implicit equations, either nonlinear stochastic
      differential equations resembling the McKean-Vlasov equations or non-local
      partial differential equations resembling the McKean-Vlasov-Fokker-Planck
      equations. We prove the well-posedness of the McKean-Vlasov equations, i.e. the
      existence and uniqueness of a solution. We also show the results of some
      numerical experiments that indicate that the mean-field equations are a good
      representation of the mean activity of a finite size network, even for modest
      sizes. These experiments also indicate that the McKean-Vlasov-Fokker-Planck
      equations may be a good way to understand the mean-field dynamics through, e.g. a
      bifurcation analysis.Mathematics Subject Classification (2000): 60F99, 60B10,
      92B20, 82C32, 82C80, 35Q80.

PMID- 22657697
TI  - In-situ inc.

PMID- 22657696
TI  - WILEY-INTERSCIENCE a division of John Wiley & Sons, Inc.

PMID- 22657699
TI  - Books & journals catalog from the american chemical society.

PMID- 22657700
TI  - Letters.

PMID- 22657701
TI  - Editorial.

PMID- 22657702
TI  - Washington.

PMID- 22657703
TI  - States.

PMID- 22657704
TI  - Science.

PMID- 22657705
TI  - Technology.

PMID- 22657706
TI  - Business.

PMID- 22657707
TI  - Evidence for improved ambient air.

PMID- 22657708
TI  - Water-quality-based toxicity testing.

PMID- 22657709
TI  - RCRA groundwater protection standards.

PMID- 22657710
TI  - Structure-activity relationships.

PMID- 22657711
TI  - Groundwater and the law.

PMID- 22657712
TI  - KRATOS Analytical Instruments.

PMID- 22657714
TI  - Products.

PMID- 22657713
TI  - are water soluble. For instance.

PMID- 22657715
TI  - Literature.

PMID- 22657720
TI  - 2012 Beers criteria update: how should practicing nurses use the criteria?
AB  - The continued development of explicit lists of medications to avoid in older
      adults, such as the Beers criteria, is a key initiative in geriatrics. The
      involvement of nurse in this endeavor is critical , and nursing research,
      education, and practice will help not only develop but also disseminate important
      pharmacological management information to the public and thereby decrease drug
      related problems and improve the health of older adults. Lastly, we wish to
      acknowledge Dr. Mark Beers' tremendous leadership in conceptualizing the
      importance of medication management in older adults and in acknowledging the
      significance of the full-team approach in patient care. Mark, who passed away in
      2009, was an incredible mentor and true champion of safe medication use in
      adults.

PMID- 22657721
TI  - Stumped by salary estimates.

PMID- 22657725
TI  - Diffuse large B-cell lymphoma in an adolescent female presenting with Epstein
      Barr virus-driven hemophagocytic lymphohistiocytosis: a case report.
AB  - INTRODUCTION: Hemophagocytic lymphohistiocytosis is characterized by multisystem
      inflammation, resulting from prolonged and intense activation of macrophages,
      histiocytes and CD8+ T-cells. Due to its variable presentation and non-specific
      findings, timely diagnosis can be challenging. This condition has been associated
      with malignancies, most commonly with lymphomas and leukemias of T-cell lineage.
      This case report represents the less commonly associated B-cell lymphomas. We
      also highlight the difficulties in managing hemophagocytosis with an evolving
      malignancy. This case report will add to the increasing literature on the
      diagnosis, complications and management of this complex disorder. CASE
      PRESENTATION: A 15-year-old Caucasian girl, previously diagnosed with Crohn's
      disease and treated with 6-mercaptopurine, developed Epstein-Barr virus infection
      driven hemophagocytic lymphohistiocytosis. The diagnosis was challenging due to
      her critical illness and the lack of enough features to fulfill diagnostic
      criteria at presentation (moderately elevated ferritin, normal coagulation
      profiles and normal triglycerides). While receiving therapy for hemophagocytic
      lymphohistiocytosis, she developed bulky cervical lymphadenopathy and was
      diagnosed with diffuse large B-cell lymphoma. Therapy for lymphoma was initiated
      and she tolerated the therapy well. CONCLUSION: Hemophagocytic
      lymphohistiocytosis is a rare disorder, but potentially lethal if not diagnosed
      and treated in a timely manner. Our case highlights the importance of considering
      this diagnosis in critically ill patients who may not initially fulfill formal
      diagnostic criteria. In patients diagnosed with hemophagocytic
      lymphohistiocytosis, occult malignancies should be aggressively ruled out as they
      can manifest prior to the hemophagocytic lymphohistiocytosis diagnosis or appear
      during the treatment phase. An accurate diagnosis is also important because
      management of Epstein-Barr virus-driven hemophagocytic lymphohistiocytosis and
      Epstein-Barr virus-driven lymphoma differs due to the difference in
      pathophysiology and the involvement of different immune cell lines.

PMID- 22657726
TI  - Individual surgical decision-making and comparative effectiveness research.

PMID- 22657727
TI  - Parathyroid hormone decline 4 hours after total thyroidectomy accurately predicts
      hypocalcemia.
AB  - BACKGROUND: The level of parathyroid hormone (iPTH) serum has been controversial
      in the prediction of postthyroidectomy hypocalcemia. Analysis of the decrease
      between preoperative and postoperative iPTH levels should be more accurate.
      Therefore, the aim of our study was to prospectively establish the reliability of
      the iPTH decrease for early diagnosis of postoperative hypocalcemia and to
      identify the patients who are not at risk for hypocalcemia. METHODS: A
      prospective study of 137 consecutive patients who underwent total thyroidectomy
      was performed. Serum iPTH level was measured preoperatively and 4 hours
      postoperatively (iPTH(H4)). The sensitivity, specificity, and positive and
      negative predictive values for the iPTH(H4) and for the iPTH decline were
      estimated by confidence interval from thresholds determined by ROC curve
      analysis. RESULTS: Thirty-nine patients developed hypocalcemia (28.5%). Patients
      who developed hypocalcemia had a significantly lower iPTH(H4) and a significantly
      greater iPTH decrease (P < .001). The thresholds enabling prediction of
      hypocalcemia were 19.4 ng/L for iPTH(H4) and 68.5% for iPTH decline. Sensitivity,
      specificity, and positive and negative predictive values for iPTH(H4) were 84.6%,
      92.9%, 82.5%, and 93.8% (overall accuracy, 90.5%). iPTH decline was more accurate
      to predict hypocalcemia (sensitivity, 97.4%; specificity, 95.9%; positive
      predictive values 90.5%; negative predictive values, 98.6%; and overall accuracy,
      96.4%). CONCLUSION: The decrease in iPTH is more precise than the iPTH(H4) alone
      and can accurately predict hypocalcemia after total thyroidectomy. Patients with
      a decrease in iPTH less than 68.5% can be discharged at postoperative day one
      without any supplementation. Patients with iPTH decline more than 68.5% should be
      administered calcium and vitamin D supplementation before symptoms appear.

PMID- 22657728
TI  - Chronic calcific pancreatitis of tropics.

PMID- 22657729
TI  - Bilirubin level in the drainage fluid is an early and independent predictor of
      clinically relevant bile leakage after hepatic resection.
AB  - BACKGROUND: Variations in the definition of bile leakage after hepatic resection
      have prevented the identification of risk factors for early diagnosis and
      efficient management. The International Study Group of Liver Surgery (ISGLS)
      definition standardizes reporting of this complication. It was our aim in the
      present study to prospectively validate the ISGLS definition of bile leakage
      after hepatic resection. Furthermore, we sought to identify early predictors of
      clinically relevant bile leakage. METHODS: A total of 265 patients who underwent
      elective hepatic resection were enrolled prospectively. Bilirubin concentrations
      were determined in the serum and drainage fluid until postoperative day 5. Risk
      factors of Grade B/C bile leakage were assessed by the use of univariate and
      multivariate analyses. RESULTS: Grade A, B, and C bile leakage was diagnosed in
      23 (8.7%), 38 (14.3%), and 11 (4.1%) patients, respectively. The definition as
      well as severity grading of bile leakage correlated with the duration of drainage
      and intensive care unit and hospital stay. Perioperative mortality was 0% for
      Grade A, 5.2% for Grade B, and 45.4% for Grade C bile leakage (P < .0001).
      Multivariate analysis confirmed bilirubin concentration in the drainage fluid
      >=2.4 mg/dL on postoperative day 2 (odds ratio 11.88; 95% confidence interval
      5.33-26.49; P < .0001) and anatomic resection (odds ratio 3.59; 95% CI 1.08
      11.97; P = .04) as independent predictors of clinically relevant bile leakage.
      CONCLUSION: The ISGLS definition and severity grading of bile leakage after
      hepatic resection is clinically meaningful. Bilirubin concentration in the
      drainage fluid on postoperative day 2 is a strong predictor of clinically
      relevant bile leakage.

PMID- 22657730
TI  - Population-based esophageal cancer survival after resection without neoadjuvant
      therapy: an update.
AB  - BACKGROUND: There are few population-based studies addressing the survival after
      resection for esophageal cancer. This study represents an update of a nationwide
      Swedish cohort initiated in 1987. METHODS: Based on data from the Swedish Patient
      Register, Swedish Cancer Register, and histopathologic records, 1,008 patients
      who had undergone esophageal resection as the only treatment for esophageal
      cancer were identified between January 1, 1987 and December 31, 2005. These were
      followed until death or emigration through linkage to the Swedish Total
      Population Register until January 1, 2009. Tumor stage, location, and histology
      were assessed from histopathologic reports, and comorbidities were assessed from
      the Patient Register. Cox proportional hazards regression models were used to
      calculate hazard ratios (HRs) with 95% confidence intervals (CIs) regarding
      survival. The results were adjusted for age, sex, comorbidity, tumor stage,
      location, histology, surgical radicality, and hospital volume. RESULTS: The
      proportion of patients surviving for 5 years increased from 19.7% in 1987-1991 to
      30.7% in 1997-2000, but remained at 30.5% between 2001 and 2005. No difference in
      overall adjusted survival was found between the periods of 2001-2005 and 1997
      2000 (adjusted HR, 0.89; 95% CI, 0.70-1.13). Thirty-day mortality decreased from
      4.9% in 1997-2000 to 2.0% in 2001-2005, rendering an adjusted HR of 0.26 (95% CI,
      0.08-0.87). CONCLUSION: After adjusting for relevant prognostic factors, long
      term population-based survival after resection for esophageal cancer was
      unchanged between 2001 and 2005 compared to 1997-2000, while the corresponding 30
      day mortality improved.

PMID- 22657731
TI  - Pharmacologic resuscitation decreases circulating cytokine-induced neutrophil
      chemoattractant-1 levels and attenuates hemorrhage-induced acute lung injury.
AB  - BACKGROUND: Acute lung injury (ALI) is a complication of hemorrhagic shock (HS).
      Histone deacetylase inhibitors, such as valproic acid (VPA), can improve survival
      after HS; however, their effects on late organ injury are unknown. Herein, we
      have investigated the effects of HS and VPA treatment on ALI and circulating
      cytokines that may serve as biomarkers for the development of organ injury.
      METHODS: Anesthetized Wistar-Kyoto rats (250-300 g) underwent 40% blood volume
      hemorrhage over 10 minutes followed by 30 minutes of unresuscitated shock and
      were treated with either VPA (300 mg/kg) or vehicle control. Blood samples were
      obtained at baseline, after shock, and before death (at 1, 4, and 20 hours; n = 3
      4/timepoint/group). Serum samples were screened for possible biomarkers using a
      multiplex electrochemiluminescence detection assay, and results were confirmed
      using enzyme-linked immunosorbent assay (ELISA). In addition, lung tissue lysate
      was examined for chemokine and myeloperoxidase (MPO) levels as a marker for
      neutrophil infiltration and ALI. Lung cytokine-induced neutrophil chemoattractant
      1 (CINC-1; a chemokine belonging to the interleukin-8 family that promotes
      neutrophil chemotaxis) mRNA levels were measured by real-time polymerase chain
      reaction studies. RESULTS: Serum screening revealed that hemorrhage rapidly
      altered levels of circulating CINC-1. ELISA confirmed that CINC-1 protein was
      significantly elevated in the serum as early as 4 hours and in the lung at 20
      hours after hemorrhage, without any significant changes in CINC-1 mRNA
      expression. Lung MPO levels were also elevated at both 4 and 20 hours after
      hemorrhage. VPA treatment attenuated these changes. CONCLUSION: Hemorrhage
      resulted in the development of ALI, which was prevented with VPA treatment.
      Circulating CINC-1 levels rose rapidly after hemorrhage, and serum CINC-1 levels
      correlated with lung CINC-1 and MPO levels. This suggests that circulating CINC-1
      levels could be used as an early marker for the subsequent development of organ
      inflammation and injury.

PMID- 22657732
TI  - Interaction specificity between the chaperone and proteolytic components of the
      cyanobacterial Clp protease.
AB  - The Clp protease is conserved among eubacteria and most eukaryotes, and uses ATP
      to drive protein substrate unfolding and translocation into a chamber of
      sequestered proteolytic active sites. In plant chloroplasts and cyanobacteria,
      the essential constitutive Clp protease consists of the Hsp100/ClpC chaperone
      partnering a proteolytic core of catalytic ClpP and noncatalytic ClpR subunits.
      In the present study, we have examined putative determinants conferring the
      highly specific association between ClpC and the ClpP3/R core from the model
      cyanobacterium Synechococcus elongatus. Two conserved sequences in the N-terminus
      of ClpR (tyrosine and proline motifs) and one in the N-terminus of ClpP3 (MPIG
      motif) were identified as being crucial for the ClpC-ClpP3/R association. These N
      terminal domains also influence the stability of the ClpP3/R core complex itself.
      A unique C-terminal sequence was also found in plant and cyanobacterial ClpC
      orthologues just downstream of the P-loop region previously shown in Escherichia
      coli to be important for Hsp100 association to ClpP. This R motif in
      Synechococcus ClpC confers specificity for the ClpP3/R core and prevents
      association with E. coli ClpP; its removal from ClpC reverses this core
      specificity.

PMID- 22657733
TI  - Focus issue: Structure and function of lymphoid tissues.

PMID- 22657734
TI  - Mining electronic laboratory notebooks: analysis, retrosynthesis, and reaction
      based enumeration.
AB  - An approach to automatically analyze and use the knowledge contained in
      electronic laboratory notebooks (ELNs) has been developed. Reactions were reduced
      to their reactive center and converted to a string representation (SMIRKS) which
      formed the basis for reaction classification and in silico (retro-)synthesis. Of
      the SMIRKS that occurred at least five times, 98% successfully regenerated the
      original product. The extracted reaction rules (SMIRKS) and corresponding
      reactants span a virtual chemical space which showed a strong dependence on the
      size of the reactive center. Whereas relatively few robust reaction types were
      sufficient to describe a large part of all reactions, considerably more reaction
      rules were necessary to cover all reactions in the ELN. Furthermore, reaction
      sequences were extracted to identify frequent combinations and diversifying
      reaction steps. Based on the extracted knowledge a (retro-)synthesis tool was
      built allowing for de novo design of compounds which have a high chance of being
      synthetically accessible. In an example application of the de novo design tool,
      various feasible retrosynthetic routes to the query molecule were obtained.
      Reaction based enumeration along the top ranked route yielded a library of 29 920
      compounds with diverse properties, 99.9% of which are novel in the sense that
      they are unknown to the public domain.

PMID- 22657735
TI  - Carbon dioxide induced silk protein gelation for biomedical applications.
AB  - We present a novel method to fabricate silk fibroin hydrogels using high pressure
      carbon dioxide (CO(2)) as a volatile acid without the need for chemical cross
      linking agents or surfactants. The simple and efficient recovery of CO(2) post
      processing results in a remarkably clean production method offering tremendous
      benefit toward materials processing for biomedical applications. Further, with
      this novel technique we reveal that silk protein gelation can be considerably
      expedited under high pressure CO(2) with the formation of extensive beta-sheet
      structures and stable hydrogels at processing times less than 2 h. We report a
      significant influence of the high pressure CO(2) processing environment on silk
      hydrogel physical properties such as porosity, sample homogeneity, swelling
      behavior and compressive properties. Microstructural analysis revealed improved
      porosity and homogeneous composition among high pressure CO(2) specimens in
      comparison to the less porous and heterogeneous structures of the citric acid
      control gels. The swelling ratios of silk hydrogels prepared under high pressure
      CO(2) were significantly reduced compared to the citric acid control gels, which
      we attribute to enhanced physical cross-linking. Mechanical properties were found
      to increase significantly for the silk hydrogels prepared under high pressure
      CO(2), with a 2- and 3-fold increase in the compressive modulus of the 2 and 4 wt
      % silk hydrogels over the control gels, respectively. We adopted a semiempirical
      theoretical model to elucidate the mechanism of silk protein gelation
      demonstrated here. Mechanistically, the rate of silk protein gelation is believed
      to be a function of the kinetics of solution acidification from absorbed CO(2)
      and potentially accelerated by high pressure effects. The attractive features of
      the method described here include the acceleration of stable silk hydrogel
      formation, free of residual mineral acids or chemical cross-linkers, reducing
      processing complexity, and avoiding adverse biological responses, while providing
      direct manipulation of hydrogel physical properties for tailoring toward specific
      biomedical applications.

PMID- 22657736
TI  - Contextual data integration in drug discovery.
AB  - INTRODUCTION: The interpretation of high-throughput profiling data depends on the
      pathway analysis database. Currently, pathway analysis often has to rely on a set
      of interactions and pathways measured in every possible human tissue, due to
      insufficient knowledge about interactions and pathways in the context of the
      profiling experiment. However, a recent global scale analysis of human tissue
      proteomes and interactomes reveals significant differences among tissues,
      suggesting that interaction and pathway data that are used out of biological
      context are the major source of inaccuracies and noise in the analysis of
      profiling data. AREAS COVERED: In this review, the major classes of biological
      context used for experimental detection of molecular interactions and pathways in
      molecular biology are described. Furthermore, the author reviews methods for
      predicting biological interactions in order to evaluate the applicability of
      various contextual interaction data in pathway analysis. Using the results from
      recent publications that study large-scale tissue composition, the article
      provides an estimation of the gain in pathway analysis accuracy if only the
      interactions predicted for the context of a molecular profiling experiment are
      used, relative to the analysis performed with a context-independent knowledge
      base. EXPERT OPINION: It is of the author's opinion that the major source of
      inaccuracy in pathway analysis is the lack of knowledge about tissue-specific
      transcriptional regulation. It is therefore suggested that the accuracy of the
      analysis can be substantially improved if only context-specific interactions and
      pathways are used for interpretation.

PMID- 22657738
TI  - [Evaluation of the incidence of upper gastrointestinal bleeding in Spain in
      relation to the taking of anti-ulcer agents].
AB  - OBJECTIVE: To analyse trends in the incidence of hospitalisation due to upper
      gastrointestinal bleeding (UGB) and the relationship with the prescribing of anti
      ulcer agents. DESIGN: Retrospective observational ecological study. SETTING:
      Spanish National Health System (NHS) for the nine years between 1st January 2000
      and 31st December 2008. PARTICIPANTS:  INCLUSION CRITERIA: Patients aged 15 or
      over hospitalised due to UGB were divided into four age groups: 15-44, 45-64, 65
      74 and >=75 years old. Drugs, A02B subgroup, prescribed under the NHS. EXCLUSION
      CRITERIA: Prescription of medicines in hospital or public-employee insurance
      companies. MEASUREMENTS: Incidence (number of new cases of UGB occurring in one
      year), Incidence rate (incidence per 100,000 inhabitants), Dispersion rate
      (number of packets dispensed per year per 100,000 inhabitants), and Hazard ratio
      (HR, ratio between the rate of the last year over the first year. Annual rates
      were calculated by the standardised direct method). DATA SOURCE: Ministry of
      Health. RESULTS: We identified 110,150 hospital admissions due to UGB (61.17%
      male, 38.83% female). Values for 95% UGB: Total Mean Incidence Rate (MIR)=34.45
      [32.70, 36.20], HR=0.83. Males: MIR=43.07 [40.41, 45.72], HR=0.80 and females:
      MIR=25.20 [25.18, 27.23], HR=0.88. HR HDA by age group in males: 15-44
      years=0.64; 45-64 years=0.74, 65-74 years=0.74 and >74 years=0.85. Females: 15-44
      years=0.82, 45-64 years=0.71, 65-74 years=0.3 and >74 years=0.89. Drug dispensing
      (2000-2008): HR proton pump inhibitors=4.43; HR all anti-ulcer agents=3.01.
      CONCLUSIONS: Over nine years the dispensing of anti-ulcer agents by the Spanish
      National Health System has multiplied without having regard to the evolutionary
      trend of hospitalisation due to UGB.

PMID- 22657746
TI  - Safety of transient abdominal ovariopexy in patients with severe endometriosis.
AB  - OBJECTIVE: To evaluate complications of transient ovariopexy performed to reduce
      adhesions in patients with severe endometriosis. METHODS: A bicentric
      retrospective study involved 193 consecutive patients who underwent laparoscopic
      surgery for severe endometriosis at 2 French university hospitals from 1997 to
      2009. At the end of surgery, unilateral or bilateral transient ovariopexy was
      performed on 297 ovaries. Immediate (e.g. reproducibility, tolerance, and
      hospital stay) and long-term (evaluated via vaginal access to the ovaries,
      ovarian function, and ovarian vascularization) complications were assessed.
      RESULTS: The technique, which was easy and reproducible, did not increase
      hospital stay and was well tolerated. There were 2 (0.7%) immediate
      complications. There was no difference in ovarian accessibility before and after
      surgery (177/183 [96.7%] vs 176/183 [96.1%]). Potential vaginal oocyte retrieval
      for in vitro fertilization was possible for all patients. The antral follicle
      count and the pulsatility index of suspended ovaries were not different from
      those of contralateral unsuspended ovaries. Endometrioma excision did not modify
      these results. CONCLUSION: The short- and long-term safety results of transient
      ovariopexy for adnexal adhesions in patients with severe endometriosis were
      encouraging.

PMID- 22657737
TI  - Redox regulation of Ras and Rho GTPases: mechanism and function.
AB  - SIGNIFICANCE: Oxidation and reduction events are critical to physiological and
      pathological processes and are highly regulated. Herein, we present evidence for
      the role of Ras and Rho GTPases in controlling these events and the unique
      underlying mechanisms. Evidence for redox regulation of Ras GTPases that contain
      a redox-sensitive cysteine (X) in the conserved NKXD motif is presented, and a
      growing consensus supports regulation by a thiyl radical-mediated oxidation
      mechanism. We also discuss the debate within the literature regarding whether 2e(
      ) oxidation mechanisms also regulate Ras GTPase activity. RECENT ADVANCES: We
      examine the increasing in vitro and cell-based data supporting oxidant-mediated
      activation of Rho GTPases that contain a redox-sensitive cysteine at the end of
      the conserved phosphoryl-binding loop (p-loop) motif (GXXXXG[S/T]C). While this
      motif is distinct from Ras, these data suggest a similar 1e(-) oxidation-mediated
      activation mechanism. CRITICAL ISSUES: We also review the data showing that the
      unique p-loop placement of the redox-sensitive cysteine in Rho GTPases supports
      activation by 2e(-) cysteine oxidation. Finally, we examine the role that Ras and
      Rho GTPases play in controlling key oxidant-regulating enzymes in the cell, and
      we speculate on a feedback mechanism. FUTURE DIRECTIONS: Given that these GTPases
      and redox-regulating enzymes are involved in multiple physiological and
      pathological processes, we discuss future experiments that may clarify the
      interplay between them.

PMID- 22657747
TI  - Developmental exposure to mercury chloride does not impair social behavior of
      C57BL/6 * BTBR F(1) mice.
AB  - The effects of mercury (Hg) on social behavior and the mechanisms involved remain
      unknown. This study shows that Hg chloride (HgCl(2)) exposure during fetal
      development does not impair social behavior of a mouse strain susceptible to
      environment-induced autistic-like behavior based on the parental phenotype. On
      the contrary, Hg exposure elevated the sociability of females. Since B6 mice are
      behaviorally normal and BTBR mice display low levels of sociability, the F(1)
      offspring (B6BF(1)) of female B6 mice and male BTBR mice were used to investigate
      their social behavior and the effects of Hg. Developmental Hg-treatment increased
      the serum IgG levels of the post-natal day (pnd) 21 offspring, but not pnd70
      offspring or the B6 dams. After Hg treatment, there were negligible levels of
      serum IgG anti-brain antibodies (Ab) in the pnd21 and pnd70 offspring as well as
      their dams. However, Hg did elevate IgG deposition in multiple assayed brain
      regions of the pnd21 offspring, but the higher levels were no longer present at
      pnd70. Cytokine levels were not changed in pnd21 or pnd70 brain by Hg exposure,
      suggesting neuroinflammation was not induced. Social behavior was assayed at
      pnd70. Surprisingly, Hg-treatment significantly enhanced sociability of female
      B6BF(1) offspring, but not that of the male offspring. Our data indicates that
      developmental exposure to HgCl(2) did not impair social behavior of B6BF(1)
      offspring, but it enhanced the sociability of females, which was significantly
      lower in adult B6BF(1) females than B6BF(1) males in the absence of any Hg
      exposure.

PMID- 22657749
TI  - Fabrication of a uniformly sized fenofibrate microemulsion by membrane
      emulsification.
AB  - Fenofibrate-loaded microemulsions composed of Labrafil M 1944 CS, Capryol PGMC
      and fenofibrate as the dispersed phase and Labrasol in demineralised water as the
      continuous phase were prepared by utilising a Shirasu-porous-glass (SPG) membrane
      emulsification technique. The process parameters were optimised by adjusting the
      feed pressure (15-45 kPa), agitator speed (250-800 rpm) and temperature of the
      continuous phase (25-45 degrees C). As a result, narrowly distributed
      microemulsions were obtained via SPG membrane emulsification at an agitator speed
      of 250 rpm, a feed pressure of 30 kPa and a continuous phase temperature of 25
      degrees C. Furthermore, TEM images clearly showed that the microemulsion prepared
      by SPG membrane emulsification had a uniform, spherical morphology with a narrow
      size distribution. Our results indicated that the SPG membrane emulsification
      technique is highly efficient for the preparation of narrowly distributed
      microemulsions with relatively smaller particle sizes compared with the common
      stirring method.

PMID- 22657748
TI  - Stimulant abuser groups to engage in 12-step: a multisite trial in the National
      Institute on Drug Abuse Clinical Trials Network.
AB  - AIMS: The study evaluated the effectiveness of an 8-week combined group plus
      individual 12-step facilitative intervention on stimulant drug use and 12-step
      meeting attendance and service. DESIGN: Multisite randomized controlled trial,
      with assessments at baseline, mid-treatment, end of treatment, and 3- and 6-month
      post-randomization follow-ups (FUs). SETTING: Intensive outpatient substance
      treatment programs. PARTICIPANTS: Individuals with stimulant use disorders (n =
      471) randomly assigned to treatment as usual (TAU) or TAU into which the
      Stimulant Abuser Groups to Engage in 12-Step (STAGE-12) intervention was
      integrated. MEASUREMENTS: Urinalysis and self-reports of substance use and 12
      step attendance and activities. INTERVENTION: Group sessions focused on
      increasing acceptance of 12-step principles; individual sessions incorporated an
      intensive referral procedure connecting participants to 12-step volunteers.
      FINDINGS: Compared with TAU, STAGE-12 participants had significantly greater odds
      of self-reported stimulant abstinence during the active 8-week treatment phase;
      however, among those who had not achieved abstinence during this period, STAGE-12
      participants had more days of use. STAGE-12 participants had lower Addiction
      Severity Index Drug Composite scores at and a significant reduction from baseline
      to the 3-month FU, attended 12-step meetings on a greater number of days during
      the early phase of active treatment, engaged in more other types of 12-step
      activities throughout the active treatment phase and the entire FU period, and
      had more days of self-reported service at meetings from mid-treatment through the
      6-month FU. CONCLUSIONS: The present findings are mixed with respect to the
      impact of integrating the STAGE-12 intervention into intensive outpatient drug
      treatment compared with TAU on stimulant drug use. However, the results more
      clearly indicate that individuals in STAGE-12 had higher rates of 12-step meeting
      attendance and were engaged in more related activities throughout both the active
      treatment phase and the entire 6-month FU period than did those in TAU.

PMID- 22657750
TI  - Effects of loading procedures of magnetic nanoparticles on the structure and
      physicochemical properties of cisplatin magnetic liposomes.
AB  - The effects of different loading procedures of magnetic nanoparticles (MNs) on
      the structure and physicochemical properties of cisplatin magnetic liposomes were
      investigated by X-ray diffraction, infrared spectroscopy, transmission electron
      microscopy, and fluorescence spectroscopy. 1, 2-Dipalmitoyl-sn-glycero-3
      Phosphocholine based cisplatin magnetic liposomes were prepared using two
      different procedures. In procedure I, MNs were combined with phospholipids during
      film formation; MNs were embedded in a phospholipid bilayer. In procedure II, MNs
      were mixed with drugs during hydration and MNs were contained in an interior
      aqueous compartment. The encapsulation efficiency of cisplain and the content of
      MN in procedure I liposomes were 33.5% +/- 3.3% and 2.34 +/- 0.09 mg mL(-1),
      respectively. It indicated that the deliberate MN loading into the liposome
      structure was not only successful using procedure I, but also superior over
      procedure II both in cisplatin encapsulation efficiency and MN content, which can
      promote the magnetic targeting effect of magnetic liposomes during delivering
      cisplatin.

PMID- 22657751
TI  - Formulation of meningococcal capsular polysaccharide vaccine-loaded
      microparticles with robust innate immune recognition.
AB  - Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis
      associated with a high mortality rate. Capsular polysaccharides (CPSs) are a
      major virulence factor and form the basis for serogroup designation and
      protective vaccines. The current polysaccharide meningococcal vaccines are
      available but are very expensive and require chemical conjugation. Here, we
      report a novel meningococcal vaccine formulation consisting of meningococcal CPS
      polymers encapsulated in albumin-based biodegradable microparticles that slowly
      release antigen and induce robust innate immune responses. Vaccines that elicit
      innate immunity are reported to have enhanced and protective adaptive immune
      responses. In this study, the meningococcal CPS-loaded microparticles, but not
      the empty microparticles, induced the release of IL-8, TNF-alpha and IL-1beta,
      enhanced phagocytic capacity and induced robust autophagy in macrophages. The
      novel meningococcal vaccine microparticles are robustly taken up by macrophages
      and elicit strong innate immune responses that enhance antigen presentation which
      is a prerequisite for inducing adaptive immunity.

PMID- 22657752
TI  - Triple junction transport and the impact of grain boundary width in
      nanocrystalline Cu.
AB  - Triple junctions (TJ), singular topological defects of the grain boundary (GB)
      structure, get a dominant role for grain growth and atomic transport in
      nanocrystalline matter. Here, we present detailed measurements by atom probe
      tomography, even of the temperature dependence of TJ transport of Ni in
      nanocrystalline Cu in the chemical regime of interdiffusion. An unexpected
      variation of the effective width of merging GBs with temperature is detected. It
      is demonstrated that proper measurement of TJ transport requires taking into
      account this remarkable effect. TJ diffusion is found to be a factor of about 200
      faster than GB diffusion. Its activation energy amounts to only two-thirds of
      that of the GB.

PMID- 22657827
TI  - Gradient estimation in dendritic reinforcement learning.
AB  - We study synaptic plasticity in a complex neuronal cell model where NMDA-spikes
      can arise in certain dendritic zones. In the context of reinforcement learning,
      two kinds of plasticity rules are derived, zone reinforcement (ZR) and cell
      reinforcement (CR), which both optimize the expected reward by stochastic
      gradient ascent. For ZR, the synaptic plasticity response to the external reward
      signal is modulated exclusively by quantities which are local to the NMDA-spike
      initiation zone in which the synapse is situated. CR, in addition, uses nonlocal
      feedback from the soma of the cell, provided by mechanisms such as the
      backpropagating action potential. Simulation results show that, compared to ZR,
      the use of nonlocal feedback in CR can drastically enhance learning performance.
      We suggest that the availability of nonlocal feedback for learning is a key
      advantage of complex neurons over networks of simple point neurons, which have
      previously been found to be largely equivalent with regard to computational
      capability.

PMID- 22657828
TI  - Recruitment of HRDC domain of WRN and BLM to the sites of DNA damage induced by
      mitomycin C and methyl methanesulfonate.
AB  - The HRDC (helicase and RNase D C-terminal) domain at the C-terminal of WRNp
      (Werner protein) (1150-1229 amino acids) and BLMp (Bloom protein) (1212-1292
      amino acids) recognize laser microirradiation-induced DNA dsbs (double-strand
      breaks). However, their role in the recognition of DNA damage other than dsbs has
      not been reported. In this work, we show that HRDC domain of both the proteins
      can be recruited to the DNA damage induced by MMS (methyl methanesulfonate) and
      MMC (methyl mitomycin C). GFP (green fluorescent protein)-tagged HRDC domain
      produces distinct foci-like respective wild-types after DNA damage induced by the
      said agents and co-localize with gamma-H2AX. However, in time course experiment,
      we observed that the foci of HRDC domain exist after 24 h of removal of the
      damaging agents, while the foci of full-length protein disappear completely. This
      indicates that the repair events are not completed by the presence of protein
      corresponding to only the HRDC domain. Consequently, cells overexpressing the
      HRDC domain fail to survive after DNA damage, as determined by MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay. Moreover, 24 h
      after removal of damaging agents, the extent of DNA damage is greater in cells
      overexpressing HRDC domain compared with corresponding wild-types, as observed by
      comet assay. Thus, our observations suggest that HRDC domain of both WRN and BLM
      can also recognize different types of DNA damages, but for the successful repair
      they fail to respond to subsequent repair events.

PMID- 22657829
TI  - One step forward for interdisciplinary geriatrics.

PMID- 22657830
TI  - Prevalence of antipsychotic use in long-term care residents with Parkinson
      dementia.

PMID- 22657831
TI  - Medicare's increasing focus on prevention and wellness services should garner
      greater attention by health care practitioners and communities.

PMID- 22657832
TI  - Remembering what's important in Alzheimer's dementia management in assisted
      living.

PMID- 22657833
TI  - Patients with advanced dementia: how do we know if they are in pain?

PMID- 22657834
TI  - Subdural spread of injected local anesthetic in a selective transforaminal
      cervical nerve root block: a case report.
AB  - INTRODUCTION: Although uncommon, selective cervical nerve root blocks can have
      serious complications. The most serious complications that have been reported
      include cerebral infarction, spinal cord infarction, transient quadriplegia and
      death. CASE PRESENTATION: A 40-year-old Japanese woman with a history of severe
      right-sided cervical radicular pain was scheduled to undergo a right-sided C6
      selective cervical nerve root block using a transforaminal approach under
      fluoroscopic guidance. An anterior oblique view of the C5-C6 intervertebral
      foramen was obtained, and a 23-gauge spinal needle, connected to the normal
      extension tube with a syringe filled with contrast medium, was introduced into
      the posterior-caudal aspect of the C5-C6 intervertebral foramen on the right
      side. In the anteroposterior view, the placement of the needle was considered
      satisfactory when it was placed no more medial than halfway across the width of
      the articular pillar. Although the spread of the contrast medium along the C6
      nerve root was observed with right-sided C6 radiculography, the subdural flow of
      the contrast medium was not observed with real-time fluoroscopy. The extension
      tube used for the radiculography was removed from the spinal needle and a normal
      extension tube with a syringe filled with lidocaine connected in its place. We
      performed a negative aspiration test and then injected 1.5 mL of 1.0% lidocaine
      slowly around the C6 nerve root. Immediately after the injection of the local
      anesthetic, our patient developed acute flaccid paralysis, complained of
      breathing difficulties and became unresponsive; her respiratory pattern was
      uncoordinated. After 20 minutes, she regained consciousness and became alert, and
      her muscle strength in all four limbs returned to normal without any sensory
      deficits after receiving emergent cardiorespiratory support. CONCLUSIONS: We
      believe that confirming maintenance of the appropriate needle position in the
      anteroposterior view by injecting local anesthetic is important for preventing
      central needle movement. Because the potential risk of serious complications
      cannot be completely eliminated during the use of any established selective
      cervical nerve root block procedure, preparation for an emergency airway,
      ventilation and cardiovascular support is indispensable in cases of high spinal
      cord anesthesia.

PMID- 22657835
TI  - Induced pluripotent stem-induced cells show better constitutive heterochromatin
      remodeling and developmental potential after nuclear transfer than their parental
      cells.
AB  - Recently, reprogramming of somatic cells from a differentiated to pluripotent
      state by overexpression of specific external transcription factors has been
      accomplished. It has been widely speculated that an undifferentiated state may
      make donor cells more efficient for nuclear transfer. To test this hypothesis, we
      derived induced pluripotent stem cells (iPS cells) from several somatic cell
      lines: mouse embryonic fibroblast (MEF), adult tail tip fibroblast (TTF), and
      brain neural stem cells (NSCs). Three dimensional (3D)-fluorescent in situ
      hybridization (FISH) and quantitative-FISH (Q-FISH) were then used to evaluate
      constitutive (pericentric and telomeric) heterochromatin organization in these
      iPS cells and in their parental differentiated cells. Here, we show that
      important nuclear remodeling and telomeres rejuvenation occur in these iPS cells
      regardless of their parental origin. When we used these cells as donors for
      nuclear transfer, we produced live-born cloned mice at much higher rates with the
      iPS-induced cells than with the parental cell lines. Interestingly, we noticed
      that developmental potential after nuclear transfer could be correlated with
      telomere length of the donor cells. Altogether, our findings suggest that
      constitutive heterochromatin organization from differentiated somatic cells can
      be reprogrammed to the pluripotent state by induction of iPS cells, which in turn
      support nuclear transfer procedure quite efficiently.

PMID- 22657836
TI  - Hallucinations and comorbid renal tubular acidosis caused by topiramate in a
      patient with psychiatric history.
AB  - Few studies have shown that topiramate may induce psychiatric symptoms and
      metabolic disorders, respectively. Here, we reported a 13-year-old female who
      presented with topiramate-induced hallucinations and comorbid renal tubular
      acidosis. She had a history of psychiatric illness and had been taking the
      medication for 3 months without prior side effects. After the discontinuation of
      topiramate, she was treated with supplementary potassium and sodium bicarbonate.
      Subsequently, her psychiatric symptoms and biochemical findings improved.
      Recognition of drug-induced psychotic symptoms and renal tubular acidosis is
      important during concomitant topiramate therapy in psychiatric clinic.

PMID- 22657837
TI  - Emerging role of protein-protein transnitrosylation in cell signaling pathways.
AB  - SIGNIFICANCE: Protein S-nitrosylation, a covalent reaction of a nitric oxide (NO)
      group with a critical protein thiol (or more properly thiolate anion), mediates
      an important form of redox-related signaling as well as aberrant signaling in
      disease states. RECENT ADVANCES: A growing literature suggests that over 3000
      proteins are S-nitrosylated in cell systems. Our laboratory and several others
      have demonstrated that protein S-nitrosylation can regulate protein function by
      directly inhibiting catalytically active cysteines, by reacting with allosteric
      sites, or via influencing protein-protein interaction. For example, S
      nitrosylation of critical cysteine thiols in protein-disulfide isomerase and in
      parkin alters their activity, thus contributing to protein misfolding in
      Parkinson's disease. CRITICAL ISSUES: However, the mechanism by which specific
      protein S-nitrosylation occurs in cell signaling pathways is less well
      investigated. Interestingly, the recent discovery of protein-protein
      transnitrosylation reactions (transfer of an NO group from one protein to
      another) has revealed a unique mechanism whereby NO can S-nitrosylate a
      particular set of protein thiols, and represents a major class of
      nitrosylating/denitrosylating enzymes in mammalian systems. In this review, we
      will discuss recent evidence for transnitrosylation reactions between (i)
      hemoglobin/anion exchanger 1, (ii) thioredoxin/caspase-3, (iii) X-linked
      inhibitor of apoptosis/caspase-3, (iv) GAPDH-HDAC2/SIRT1/DNA-PK, and (v)
      Cdk5/dynamin related protein 1 (Drp1). This review also discusses experimental
      techniques useful in characterizing protein-protein transnitrosylations. FUTURE
      DIRECTIONS: Elucidation of additional transnitrosylation cascades will further
      our understanding of the enzymes that catalyze nitrosation, thereby contributing
      to NO-mediated signaling pathways.

PMID- 22657839
TI  - Local ice melting by an antifreeze protein.
AB  - Antifreeze proteins, AFP, impede freezing of bodily fluids and damaging of
      cellular tissues by low temperatures. Adsorption-inhibition mechanisms have been
      developed to explain their functioning. Using in silico Molecular Dynamics, we
      show that type I AFP can also induce melting of the local ice surface.
      Simulations of antifreeze-positive and antifreeze-negative mutants show a clear
      correlation between melting induction and antifreeze activity. The presence of
      local melting adds a function to type I AFPs that is unique to these proteins. It
      may also explain some apparently conflicting experimental results where binding
      to ice appears both quasipermanent and reversible.

PMID- 22657838
TI  - Crosslinking with transglutaminase does not change metabolic effects of sodium
      caseinate in model beverage in healthy young individuals.
AB  - BACKGROUND: Postprandial metabolic and appetitive responses of proteins are
      dependent on protein source and processing technique prior to ingestion. Studies
      on the postprandial effects of enzymatic crosslinking of milk proteins are
      sparse. Our aim was to study the effect of transglutaminase (TG)-induced
      crosslinking of sodium caseinate on postprandial metabolic and appetite
      responses. Whey protein was included as reference protein. METHODS: Thirteen
      healthy individuals (23.3 +/- 1.1 y, BMI 21.7 +/- 0.4 kg/m2) participated in a
      single-blind crossover design experiment in which the subjects consumed three
      different isovolumic (500 g) pourable beverages containing either sodium
      caseinate (Cas, 29 g), TG-treated sodium caseinate (Cas-TG, 29 g) or whey protein
      (Wh, 30 g) in a randomized order. Blood samples were collected at baseline and
      for 4 h postprandially for the determination of plasma glucose, insulin and amino
      acid (AA) concentrations. Gastric emptying (GE) was measured using the 13 C
      breath test method. Appetite was assessed using visual analogue scales. RESULTS:
      All examined postprandial responses were comparable with Cas and Cas-TG. The
      protein type used in the beverages was reflected as differences in plasma AA
      concentrations between Wh and Cas, but there were no differences in plasma
      glucose or insulin responses. A tendency for faster GE rate after Wh was
      detected. Appetite ratings or subsequent energy intake did not differ among the
      protein beverages. CONCLUSIONS: Our results indicate that the metabolic responses
      of enzymatically crosslinked and native sodium caseinate in a liquid matrix are
      comparable, suggesting similar digestion and absorption rates and first pass
      metabolism despite the structural modification of Cas-TG.

PMID- 22657840
TI  - Wiley.

PMID- 22657841
TI  - Good news for r&d.

PMID- 22657843
TI  - International.

PMID- 22657844
TI  - Science.

PMID- 22657846
TI  - Technology.

PMID- 22657845
TI  - Federal.

PMID- 22657847
TI  - Measurement.

PMID- 22657848
TI  - Business.

PMID- 22657850
TI  - Reinventing the EPA science advisory board.

PMID- 22657849
TI  - Designer chemistry.

PMID- 22657852
TI  - An integrated approach for efficient site cleanup.

PMID- 22657851
TI  - Denmark considers producing electricity from straw.

PMID- 22657853
TI  - The environmental technology expo.

PMID- 22657854
TI  - Case study: application at a superfund cleanup.

PMID- 22657856
TI  - Development and applications of mutational spectra technology.

PMID- 22657855
TI  - Acs.

PMID- 22657857
TI  - Contributors Needed for New ES&T.

PMID- 22657858
TI  - Low-level radioactive wastes, high-level risk ?

PMID- 22657860
TI  - Instruments.

PMID- 22657861
TI  - Air pollution.

PMID- 22657862
TI  - Hazardous waste.

PMID- 22657863
TI  - Ethical guidelines to publication of chemical research.

PMID- 22657864
TI  - ES&T Information Express.

PMID- 22657865
TI  - Classified section.

PMID- 22657867
TI  - Classified section.

PMID- 22657866
TI  - ornl.

PMID- 22657869
TI  - Nanocarrier systems for delivery of siRNA to ovarian cancer tissues.
AB  - INTRODUCTION: Novel therapeutic strategies have been investigated for ovarian
      cancer to reduce toxicity and to improve outcomes for patients. Short interfering
      RNA (siRNA), which directs the sequence-specific degradation of target mRNA and
      provides specificity of gene knockdown, represents a unique class of potential
      therapeutics for ovarian cancer. However, siRNA molecules are rapidly degraded in
      plasma and are unable to passively diffuse through cellular membranes.
      Nanocarriers can efficiently protect siRNA from in vivo degradation and are able
      to deliver these active macromolecules to tumor cells even after intravenous
      administration. AREAS COVERED: Strategies of gene therapy and the role of siRNA
      in ovarian cancer treatment are introduced, followed by an overview of
      nanocarriers for siRNA delivery, the advantages of the systems and the types of
      targeting to tumor cells. Classes of nanocarriers for delivery of siRNA, their
      functionalities and modalities are discussed with emphasis on the promising
      vehicles. EXPERT OPINION: Gene silencing therapy based on siRNA represents a
      possible opportunity for treatment of ovarian cancer patients. However, this
      approach requires selection of suitable nanocarriers that can safely and
      effectively deliver siRNA to the target site to induce its effect. Very little
      work has been done in this field; therefore, it is a good direction for future
      development.

PMID- 22657870
TI  - [Distribution of the duration of nonoccupational sick leave by medical diagnosis
      (Catalonia, Spain, 2006-2008)].
AB  - We present a simple and practical tool that allows the usual distribution of the
      duration of non-occupational sick leave to be determined by medical diagnosis. A
      total of 2,646,352 episodes of medically certified sick leave, registered by the
      Catalan Institute of Medical Evaluations for the period 2006-2008, were followed
      to closure and were entered into a spreadsheet. Given its asymmetric
      distribution, the median duration of sick leave was 9 days. Musculoskeletal
      disorders were the most frequent diagnostic group (22.5%), while neoplasms had
      the longest median duration (56 days). The most common specific diagnoses were
      diarrhea-gastroenteritis (8.2%; median: 3 days) and acute rhinopharyngitis (5.2%;
      median: 4 days). The distribution of the duration of sick leave in a population
      varies by diagnosis and is asymmetric, with most episodes being much shorter than
      the mean duration. This finding is important for better clinical and
      administrative management of sick leave episodes.

PMID- 22657871
TI  - [Impact of the new smoke-free legislation (law 42/2010) on levels of second-hand
      smoke in hospitality venues].
AB  - OBJECTIVE: To evaluate pollution by second-hand smoke in a sample of hospitality
      venues before and after the implementation of smoke-free legislation. METHODS: A
      cross sectional, before-after study was conducted in 2008 and 2011 after the
      total ban. A SidePack Aerosol monitor was used both inside and outside the
      hospitality venues to measure fine breathable particles (PM2.5). A total of 43
      places with pre- and post-legislation measurements were included. RESULTS: The
      median indoor pollution in hospitality venues was 204.2MUg/m(3) in 2008 and
      18.82MUg/m(3) in 2011; the average outdoor PM2.5 concentration was 47.04MUg/m(3)
      in 2008 and 18.82MUg/m(3) in 2011. Pollution was higher in bars and cafeterias,
      followed by pubs and discos. Before the law was implemented, pollution was 4.34
      times higher indoors than outdoors; in 2011 the average indoor PM2.5
      concentration decreased by 90.88%. CONCLUSIONS: Only a complete ban is able to
      protect workers and customers against the health risks of second-hand smoke
      exposure.

PMID- 22657913
TI  - Ultrafiltration rate is a poor indicator of haemodialysis nursing quality.
      Commentary on Lindberg and Ludvigsen (2012).

PMID- 22657914
TI  - Graphene oxide and lipid membranes: interactions and nanocomposite structures.
AB  - We have investigated the interaction between graphene oxide and lipid membranes,
      using both supported lipid membranes and supported liposomes. Also, the reverse
      situation, where a surface coated with graphene oxide was exposed to liposomes in
      solution, was studied. We discovered graphene oxide-induced rupture of
      preadsorbed liposomes and the formation of a nanocomposite, bio-nonbio multilayer
      structure, consisting of alternating graphene oxide monolayers and lipid
      membranes. The assembly process was monitored in real time by two complementary
      surface analytical techniques (the quartz crystal microbalance with dissipation
      monitoring technique (QCM-D) and dual polarization interferometry (DPI)), and the
      formed structures were imaged with atomic force microscopy (AFM). From a basic
      science point of view, the results point toward the importance of electrostatic
      interactions between graphene oxide and lipid headgroups. Implications from a
      more practical point of view concern structure-activity relationship for
      biological health/safety aspects of graphene oxide and the potential of the
      nanocomposite, multilayer structure as scaffolds for advanced biomolecular
      functions and sensing applications.

PMID- 22657915
TI  - Proposing the use of hyponatremia as a marker to help identify high risk
      individuals for lung cancer.
AB  - The use of computerized tomography (CT) scans has been recently brought into
      attention to help screen high risk individuals for lung cancer. Even though they
      are highly sensitive, their cost seems to be the main hindrance. Our hypothesis
      is to see if other factors could help identify a subset amongst the high risk
      individuals. Our focus specifically is on hyponatremia. It is well known that
      patients with lung cancer can have associated hyponatremia and multiple
      mechanisms have been put forward. Our hypothesis is that the degree of
      hyponatremia can be correlated with size or aggressiveness of the tumor and if
      true, then screening high risk individuals with hyponatremia can yield more
      patients with possible lung cancer. This, therefore, may help decrease the
      associated costs as compared to imaging/screening everyone with a CT scan for
      lung cancer and have a major impact at the public health level.

PMID- 22657916
TI  - Multi-factorial causative model for back pain management; relating causative
      factors and mechanisms to injury presentations and designing time- and cost
      effective treatment thereof.
AB  - Back pain resolution has not statistically improved over many years with some
      literature suggesting chronic back pain to be increasing. From a search of
      literature on causes, events, mechanisms, factors and treatment for back pain, a
      model is developed that relates causes of back injury to factors that result in
      pain through two primary mechanisms; muscle fatigue and muscle/tendon/connective
      tissue strain or sprain with other main mechanisms being diminished reactivity
      and strength, changes in tendon/tissue mechanical properties and fear of back
      pain recurrence/fear of movement following a back pain episode. The model
      highlights the fact that back pain/injury is multi-factorial with numerous
      circular relationships. Therefore treatment should also be multi-factorial; a
      combination of physical and psychological therapy with attention to mechanisms at
      work or in daily living that exacerbate the injury and delay recovery thereof.
      Exercise is one method that can reduce muscle imbalance, improve resilience to
      muscle fatigue, and address reactivity and strength. More importantly, eccentric
      exercise can rectify musculotendinous or connective tissue injury which plays a
      role in prolonging the back injury cycle. Posture is identified as a causative
      factor for back pain with the time exposure for posture representing the largest
      portion of daily activities. From literature and from clinical observation,
      treatment methods can be improved and incorporated into integrated multi-modal
      programs. An integrated exercise program that commences with motor control
      exercise and progresses into functional movement is suggested. Furthermore a
      modification of the McKenzie extension movement may benefit back injury
      rehabilitation for a majority of lower back pain patients. Otherwise the sit-to
      stand movement is a regular and frequent exacerbating mechanism of back pain and
      likely continuously tears connective tissue during the movement thus prolonging
      the cycle of back pain and can be addressed instantly with a modification in sit
      to-stand technique.

PMID- 22657917
TI  - Improve the viability of transplanted neural cells with appropriate sized
      neurospheres coated with mesenchymal stem cells.
AB  - Consequences of central nervous system (CNS) physical injuries and
      neurodegenerative diseases are severe because the CNS has limited capacity to
      replace neurons lost through injuries or diseases. Neural stem cells (NSCs) are
      the most versatile and promising cell source for the regeneration of injured and
      diseased CNS. However, cell therapy faces many problems related to cell survival,
      control of cell fate and proper cell engraftment after transplantation. Cell
      survival is one of the most challenging technical issues as only a small
      percentage of implanted cells can survive after transplantation. These cells
      often die in the first few days after transplantation due to acute
      inflammation/immune response, trophic factor withdrawal, oxidative stress,
      excitotoxicity, hypoxia, or anoikis. To use appropriate size of cell aggregates,
      such as neurospheres, rather than individual cell suspension, may prevent anoikis
      and improve viability. Cells in aggregates or groups can form a community to
      provide paracrine signaling or trophic support for neighboring transplanted cells
      to be able to survive in the community manner. One important parameter in the
      neurosphere structure is the size or diameter. If the sphere size is too big, the
      nutrient and oxygen support for the cells in the core of the neurosphere will be
      limited or insufficient. If the sphere size is too small, the beneficial impact
      of the multicellular community may be limited. To this end, we hypothesize that
      the survival of transplanted NSCs may be improved with the transplantation of
      multicellular neurospheres as compared to the transplantation of individual cells
      in suspension, and there is an optimal range of the sphere size to get the
      highest viability for the transplanted neural cells. Another major factor is the
      immune response to the transplanted neural cells. Even with immunosuppressant
      used, host immune response can still jeopardize the viability of the transplanted
      cells. Mesenchymal stem cells (MSCs) have been demonstrated to possess
      immunosuppressive and neuroprotective properties. We further hypothesize that the
      viability of transplanted neural cells may be further improved in neurospheres
      coated with layers of MSCs on the surface of neurospheres by suppressing the host
      immune response at the transplantation site.

PMID- 22657918
TI  - A showcase of torus canards in neuronal bursters.
AB  - Rapid action potential generation - spiking - and alternating intervals of
      spiking and quiescence - bursting - are two dynamic patterns commonly observed in
      neuronal activity. In computational models of neuronal systems, the transition
      from spiking to bursting often exhibits complex bifurcation structure. One type
      of transition involves the torus canard, which we show arises in a broad array of
      well-known computational neuronal models with three different classes of bursting
      dynamics: sub-Hopf/fold cycle bursting, circle/fold cycle bursting, and fold/fold
      cycle bursting. The essential features that these models share are multiple time
      scales leading naturally to decomposition into slow and fast systems, a saddle
      node of periodic orbits in the fast system, and a torus bifurcation in the full
      system. We show that the transition from spiking to bursting in each model system
      is given by an explosion of torus canards. Based on these examples, as well as on
      emerging theory, we propose that torus canards are a common dynamic phenomenon
      separating the regimes of spiking and bursting activity.

PMID- 22657920
TI  - AVMA funds economic study of veterinary workforce.

PMID- 22657921
TI  - Effects of MRI on microchip function.

PMID- 22657922
TI  - What is your diagnosis? Ethylene glycol intoxication.

PMID- 22657923
TI  - ECG of the month.

PMID- 22657924
TI  - Pathology in practice. Dystrophin-deficient muscular dystrophy.

PMID- 22657925
TI  - Pathology in practice. Severe pyogranulomatous pneumonia, enteritis, and
      lymphadenitis with numerous acid-fast bacteria (M xenopi).

PMID- 22657926
TI  - A survey of Tennessee veterinarian and physician attitudes, knowledge, and
      practices regarding zoonoses prevention among animal owners with HIV infection or
      AIDS.
AB  - OBJECTIVE: To examine the attitudes, knowledge, and practices of Tennessee
      veterinarians and physicians engaged in clinical practice regarding the risk for
      and prevention of zoonoses in people with HIV infection or AIDS. DESIGN: Cross
      sectional survey. SAMPLE: Licensed Tennessee veterinarians and physicians engaged
      in clinical practice. PROCEDURES: A survey was mailed in January 2010 to 454
      licensed veterinarians and 1,737 licensed physicians. RESULTS: 181 of 419
      (43.20%) eligible veterinarians and 201 of 1,376 (14.61%) eligible physicians
      responded to the survey. A majority of both veterinarians (131/179 [73.18%]) and
      physicians (97/192 [50.52%]) indicated that veterinarians should always or almost
      always be involved in advising clients with HIV infection or AIDS. The majority
      of veterinarians (120/173 [69.36%]) indicated they always or almost always
      discussed with clients the potential risk to immune-compromised persons after
      diagnosing a zoonosis. A high proportion (88/94 [93.62%]) of physicians indicated
      they never or rarely initiated discussions about zoonoses with patients with HIV
      infection or AIDS. All physicians (94/94 [100%]) indicated they never or rarely
      contacted veterinarians for advice on zoonoses. Similarly, 174 of 180 (96.76%)
      veterinarians had never or rarely contacted physicians for advice on zoonoses
      risks. Only 25.97% of veterinarians and 33.33% of physicians were correctly able
      to identify zoonotic pathogens of greatest concern to people with HIV infection
      or AIDS. CONCLUSIONS AND CLINICAL RELEVANCE: We identified several implications
      for veterinary medical and medical practice that may reduce zoonoses transmission
      risks for people with HIV infection or AIDS, including increased communication
      between veterinarians and physicians, increased communication between people with
      HIV infection or AIDS and health-care providers, increased availability of client
      educational materials, and increased participation in zoonoses continuing
      education opportunities by health-care providers.

PMID- 22657928
TI  - Factors associated with methicillin-resistant versus methicillin-susceptible
      Staphylococcus pseudintermedius infection in dogs.
AB  - OBJECTIVE: To compare methicillin-resistant Staphylococcus pseudintermedius
      (MRSP) and methicillin-susceptible S pseudintermedius (MSSP) infections in dogs.
      DESIGN: Multicenter case-control study. ANIMALS: Dogs with MRSP infections were
      matched, by hospital, with 2 MSSP controls, with the infections occurring
      immediately before and after the case infection. PROCEDURES: Signalment,
      historical, clinical, treatment, and outcome data were documented. Conditional
      logistic regression was performed. A manual stepwise backward elimination
      procedure was used to build the multivariable model. RESULTS: 56 case and 112
      control dogs were enrolled. Pyoderma was the most common infection type in both
      groups. In the final multivariable model, systemic administration of
      antimicrobials within 30 days prior to infection was significantly associated
      with an MRSP versus an MSSP infection (OR, 9.9; 95% confidence interval, 3.59 to
      27.53). CONCLUSIONS AND CLINICAL RELEVANCE: The association of prior
      antimicrobial administration and MRSP infection indicated the potential impact of
      routine antimicrobial use in veterinary medicine on antimicrobial resistance and
      the need for prudent use of these important drugs. Mortality rate was not
      significantly different between MRSP and MSSP infections; the lack of a
      significant difference suggested that MRSP was inherently no more virulent than
      MSSP, provided the infection was properly diagnosed and appropriate treatment was
      started. Basic concepts such as prudent antimicrobial use and early diagnosis
      through timely submission of appropriate culture specimens therefore can be
      important measures to try to reduce the impact of this pathogen.

PMID- 22657929
TI  - An Internet-based survey of risk factors for surgical gastric dilatation-volvulus
      in dogs.
AB  - OBJECTIVE: To evaluate risk factors for gastric dilatation-volvulus (GDV) in a
      large number of privately owned dogs across a wide geographic area. DESIGN:
      Internet-based, cross-sectional study. ANIMALS: 2,551 privately owned dogs.
      PROCEDURES: A questionnaire addressed dog-specific, management, environmental,
      and personality-associated risk factors for GDV in dogs. Respondents were
      recruited through the posting of the electronic link to the questionnaire on
      websites for dog owners; the information was also disseminated at meetings of dog
      owners and via newsletters, e-mail lists for dog owners and breeders, owner
      oriented dog publications, and e-mails forwarded by participants. Descriptive
      statistics and logistic regression analysis were performed. RESULTS: Factors
      significantly associated with an increased risk of GDV were being fed dry kibble,
      anxiety, residence in the United Kingdom, being born in the 1990s, being a family
      pet, and spending at least 5 hours a day with the owner. Factors associated with
      a decreased risk of GDV were playing with other dogs and running the fence after
      meals, fish and egg dietary supplements, and spending equal time indoors and
      outdoors. A significant interaction between sex and neuter status was observed,
      with sexually intact females having the highest risk for GDV. CONCLUSIONS AND
      CLINICAL RELEVANCE: In dogs with a high risk of GDV, regular moderate daily and
      postprandial activity appeared to be beneficial. Feeding only commercial dry dog
      food may not be the best choice for dogs at risk; however, supplements with fish
      or eggs may reduced this risk. The effect of neuter status on GDV risk requires
      further characterization.

PMID- 22657930
TI  - Prevalence and antimicrobial resistance of Enterococcus spp and Staphylococcus
      spp isolated from surfaces in a veterinary teaching hospital.
AB  - OBJECTIVE: To determine the prevalence and antimicrobial resistance of
      enterococci and staphylococci collected from environmental surfaces at a
      veterinary teaching hospital (VTH). DESIGN: Longitudinal study. SAMPLE: Samples
      collected from surfaces in 5 areas (emergency and critical care, soft tissue and
      internal medicine, and orthopedic wards; surgery preparation and recovery rooms;
      and surgery office and operating rooms) of a VTH. PROCEDURES: Selected surfaces
      were swabbed every 3 months during the 3-year study period (2007 to 2009).
      Isolates of enterococci and staphylococci were identified via biochemical tests,
      and antimicrobial susceptibility was evaluated with a microbroth dilution
      technique. A subset of isolates was analyzed to assess clonality by use of pulsed
      field gel electrophoresis. RESULTS: 430 samples were collected, and isolates of
      enterococci (n = 75) and staphylococci (110) were identified. Surfaces
      significantly associated with isolation of Enterococcus spp and Staphylococcus
      spp included cages and a weight scale. Fourteen Enterococcus spp isolates and 17
      Staphylococcus spp isolates were resistant to >= 5 antimicrobials. Samples
      collected from the scale throughout the study suggested an overall increase in
      antimicrobial resistance of Enterococcus faecium over time. Clonality was
      detected for E faecium isolates collected from 2 different surfaces on the same
      day. CONCLUSIONS AND CLINICAL RELEVANCE: Although not surprising, the apparent
      increase in antimicrobial resistance of E faecium was of concern because of the
      organism's ability to transmit antimicrobial resistance genes to other pathogens.
      Results reported here may aid in identification of critical control points to
      help prevent the spread of pathogens in VTHs.

PMID- 22657931
TI  - Evaluation of Chlamydophila psittaci infection and other risk factors for
      atherosclerosis in pet psittacine birds.
AB  - OBJECTIVE: To determine whether the presence of Chlamydophila psittaci antigen,
      plasma cholesterol concentration, diet, sex, species, and age are risk factors
      for the development of atherosclerosis in pet psittacine birds. DESIGN:
      Retrospective case-control study. ANIMALS: 31 psittacine birds with
      atherosclerosis (study birds) and 31 psittacine birds without atherosclerosis
      (control birds). PROCEDURES: Necropsy reports were reviewed, birds with a
      histopathologic diagnosis of atherosclerosis were identified, and available
      medical records were reviewed. Signalment, history, clinicopathologic findings,
      and other relevant data were recorded and evaluated. Control birds did not have
      atherosclerosis and were chosen by both convenience sampling and population
      demographics. Histologic sections of great vessels from all birds (study and
      control birds) were reviewed and then submitted for immunohistochemical staining
      for the presence of C psittaci antigen. RESULTS: Result of immunohistochemical
      staining for C psittaci antigen in blood vessels was significantly associated
      with atherosclerosis. After adjusting for age, species origin, and type of
      illness, the odds of atherosclerosis was 7 times as high for birds with positive
      immunohistochemical staining for C psittaci antigen, compared with that of birds
      with negative immunohistochemical staining. Study birds and control birds
      differed significantly only with respect to plasma cholesterol concentrations.
      The median plasma cholesterol concentration of study birds (421 mg/dL) was
      significantly higher than that of control birds (223 mg/dL). CONCLUSIONS AND
      CLINICAL RELEVANCE: Infection with C psittaci and a high plasma cholesterol
      concentration may be risk factors for developing atherosclerosis in pet
      psittacine birds.

PMID- 22657932
TI  - Surgical and postoperative complications associated with tibial tuberosity
      advancement for cranial cruciate ligament rupture in dogs: 458 cases (2007-2009).
AB  - OBJECTIVE: To describe the surgical and postoperative complications encountered
      with tibial tuberosity advancement (TTA) performed in dogs with cranial cruciate
      ligament-deficient stifle joints. DESIGN: Retrospective case series. ANIMALS: 458
      dogs (TTA performed on 501 stifle joints). PROCEDURES: During the 2-year period,
      624 TTA procedures had been performed in dogs for correction of cranial cruciate
      ligament deficiency. Five hundred one stifle joints in 458 dogs fit the criteria
      for inclusion; 43 dogs had had TTAs performed on both stifle joints. Historical
      data and complications reported were analyzed. RESULTS: Following 501 TTA
      surgeries, there were 95 instances of complications reported. In 7 stifle joints,
      2 complications occurred. The most common complication was incisional infection
      and inflammation. Stifle joints with medial menisci that did not undergo medial
      meniscal release had a high incidence of subsequent injury, and meniscal tear was
      the most common complication treated by a second surgery. A partially torn
      cranial cruciate ligament left in situ at the time of TTA did not protect against
      subsequent injury of an intact, unreleased medial meniscus. Most fractures were
      identified on routine follow-up radiography and were rarely treated. In terms of
      preoperative factors, high body weight (> 40 kg [88 lb]) and a high preoperative
      patellar tendon angle were significantly associated with complications.
      CONCLUSIONS AND CLINICAL RELEVANCE: High body weight and preoperative patellar
      tendon angle were significantly associated with complications following TTA in
      dogs. Subsequent meniscal tear was the most common reason for second surgery,
      suggesting that medial meniscal release of intact menisci should be considered
      when performing TTA in dogs.

PMID- 22657933
TI  - Risk factors for colic in equids hospitalized for ocular disease.
AB  - OBJECTIVE: To evaluate the incidence of colic and risk factors for colic in
      equids hospitalized for ocular disease. DESIGN: Retrospective observational
      study. Animals-337 equids (317 horses, 19 ponies, and 1 donkey) hospitalized for
      ocular disease. PROCEDURES: Medical records of equids hospitalized for > 24 hours
      for treatment of ocular disease between January 1997 and December 2008 were
      reviewed. Information from only the first hospitalization was used for equids
      that were hospitalized for ocular disease on more than 1 occasion. Information
      gathered included the signalment, the type of ocular lesion and the treatment
      administered, and any colic signs recorded during hospitalization as well as the
      severity, presumptive diagnosis, and treatment of the colic. Statistical analysis
      was used to identify any risk factors for colic in equids hospitalized for ocular
      disease. RESULTS: 72 of 337 (21.4%) equids hospitalized for ocular disease had
      signs of colic during hospitalization. Most equids (59.7% [43/72]) had mild signs
      of colic, and most (87.5% [63/72]) were treated medically. Ten of 72 (13.9%)
      equids with colic had a cecal impaction. Risk factors for colic in equids
      hospitalized for ocular disease were age (0 to 1 year and >= 21 years) and an
      increased duration of hospitalization (>= 8 days). CONCLUSIONS AND CLINICAL
      RELEVANCE: There was a high incidence of colic in equids hospitalized with ocular
      disease in this study. Findings from this study may help identify equids at risk
      for development of colic and thereby help direct implementation of prophylactic
      measures.

PMID- 22657934
TI  - Myenteric ganglionitis as a cause of recurrent colic in an adult horse.
AB  - CASE DESCRIPTION: A 10-year-old Lipizzaner stallion was evaluated over the course
      of 1.5 years because of intermittent, recurrent colic. CLINICAL FINDINGS: The
      horse was initially treated medically for gastric ulcers; dietary changes were
      made, and a deworming protocol was instituted, without resolution of colic
      episodes. Subsequently, the horse underwent exploratory celiotomy and a large
      colon volvulus was identified with diffuse colonic wall thickening. A pelvic
      flexure biopsy sample was submitted for histologic examination, which revealed
      lymphocytic (CD3-positive T cells) myenteric ganglionitis (MG). The horse
      developed a cecal impaction after surgery, which did not resolve, despite
      aggressive medical management; subsequently a complete cecal bypass was
      performed. Cecal and colonic wall biopsy samples were evaluated histologically
      and confirmed the diagnosis of MG. After surgery, the horse developed a large
      colon impaction, which initially responded to aggressive medical treatment, and
      the horse was discharged. TREATMENT AND OUTCOME: Despite rigorous feed
      restrictions and prokinetic and corticosteroid treatment, the horse continued to
      have signs of colic and was euthanized 3 weeks after discharge from the hospital
      because of a recurrent large colon impaction. Intestinal biopsy samples obtained
      at the time of death revealed chronic changes in intramural ganglia consistent
      with generalized MG. CLINICAL RELEVANCE: MG is a rare disease in horses, causing
      gastrointestinal motility dysfunction and signs of colic, which is challenging to
      diagnose and treat successfully. Further studies are needed to identify the
      etiology of this disease and to explore treatment options.

PMID- 22657935
TI  - Diagnosis and surgical treatment of an intracranial cyst in an alpaca cria.
AB  - CASE DESCRIPTION: A 7-day-old female alpaca was examined because of an acute
      onset of diffuse central neurologic deficits. CLINICAL FINDINGS: Diagnostic
      imaging with CT and MRI identified an intracranial cyst occupying approximately
      one-third to one-half of the dorsal portion of the cranial cavity, markedly
      displacing the cerebral hemispheres bilaterally. TREATMENT AND OUTCOME: Initial
      surgical management via trephination and needle drainage was only transiently
      effective at resolving the neurologic signs. Craniotomy and drainage and removal
      of the cyst lining resulted in a sustained improvement in neurologic status, and
      the cria remained clinically normal and well grown at follow-up 5 months after
      surgery. CLINICAL RELEVANCE: This report represented the first description of the
      successful treatment of an intracranial cyst in a New World camelid.

PMID- 22657937
TI  - Bee venom therapy: neuro therapeutic benefits besides pain amelioration.

PMID- 22657936
TI  - New radiographic parameters to describe anterior acetabular rim trimming during
      hip arthroscopy.
AB  - PURPOSE: The purpose of this study was to describe additional radiographic
      parameters that may detect changes within the acetabular cavity during acetabular
      rim trimming for pincer-type femoroacetabular impingement. METHODS: Cadaveric
      hips that met the inclusion criteria were stripped of all tissue and had a
      portion of their labra removed; 5 mm of anterior acetabulum was measured in the
      12- to 3-o'clock position and resected with a Dremel device (Robert Bosch Tool,
      Mount Pleasant, IL). Anteroposterior radiographs were obtained with a C-arm image
      intensifier. Radiographic measurements were subsequently obtained using the
      anterior rim angle (ARA), anterior wall angle (AWA), and anterior margin ratio
      (AMR). RESULTS: Statistically significant changes were seen in the ARA, AWA, and
      AMR. Mean pre- and post-trimming changes were 81.0 degrees  and 85.7 degrees ,
      respectively, for the ARA; 34.8 degrees  and 29.2 degrees , respectively, for the
      AWA; and 0.66 and 0.57, respectively, for the AMR. CONCLUSIONS: Although much
      attention has been focused on the center-edge angle, the anterior aspect of the
      acetabulum has not previously been characterized. In conjunction with the center
      edge angle and Tonnis angle, the new parameters of ARA, AWA, and AMR can be used
      to provide a more comprehensive description of the acetabulum. The ARA, AWA, and
      AMR can be used to guide the surgeon intraoperatively and postoperatively in
      further clarifying acetabular morphology and in determining whether the rim
      resection was adequate. This study determined that there exist new radiographic
      parameters with significant changes in the anterior acetabulum as quantified by
      the ARA, AWA, and AMR that can be used to describe the radiographic changes after
      acetabular rim resection. CLINICAL RELEVANCE: The new parameters of ARA, AWA, and
      AMR can be used to provide a more comprehensive description of the acetabulum.
      These radiographic measurements can also be used by hip arthroscopists to better
      describe their surgical contribution to anterior rim trimming.

PMID- 22657938
TI  - Targeted suppression of MU-calpain and caspase 9 expression and its effect on
      caspase 3 and caspase 7 in satellite cells of Korean Hanwoo cattle.
AB  - The calpains play an important role in cell death and cell signalling. Caspases
      catalyse wholesale destruction of cellular proteins which is a major cause of
      cellular death. The current study looks at the function of MU-calpain and caspase
      9, using RNAi (RNA interference)-mediated silencing, and to observe the mRNA
      expression level of caspase genes during satellite cell growth. The satellite
      cells were treated with siRNA (small interfering RNA) of MU-calpain and caspase 9
      separately. There was reduction of 16 and 24% in CAPN1 (calpain1)-siRNA2 and
      CAPN1-siRNA3 transfected cells respectively, whereas it was 60 and 56% in CAPN1
      siRNA1 and CAPN1-siRNA4 transfected cells respectively. CAPN1-siRNA4 and CAPN1
      siRNA1 treated cells showed more reduction in caspase 3 and 7 gene expression.
      CARD9 (caspase recruitment domain 9)-siRNA1 and CARD9-siRNA2-treated cells showed
      reduction of 40 and 49% respectively. CARD9-siRNA1 and CARD9-siRNA2 showed an
      increase in caspase 3 gene expression, whereas CARD9-siRNA2 showed reduction in
      caspase 7 gene expression. These results suggest a strong cross-talk between MU
      calpain and the caspase enzyme systems. Suppression of target genes, such as MU
      calpain and caspase 9, might have genuine potential in the treatment of skeletal
      muscle atrophy. 

PMID- 22657939
TI  - A randomized controlled trial of two different types of web-based instructional
      methods: one with case-based scenarios and one without.
AB  - BACKGROUND: Computer-based learning (CBL) is an effective form of medical
      education. Educators have developed recommendations for instructional design but
      there is only minimal research that evaluates these recommendations. AIM: To
      evaluate the effect of case-based questions contained in computer modules on
      learning efficacy. METHODS: The authors conducted a randomized controlled trial
      in 124 medical students of two CBL PowerPoint modules-based on Medicare. The
      modules were identical except one contained 11 case-based scenarios followed by
      multiple choice questions. The primary outcome measurement was a previously
      validated, 11-item knowledge test taken at the end of the module and at the end
      of the academic year to test retention. RESULTS: The students who studied the
      module with case-based questions answered one more item correctly in the first
      test (8.9 vs. 10.00 correct answers, p = 0.001). This difference had disappeared
      by the time of the second test (4.2 vs. 4.7, p = 0.095). CONCLUSIONS: This study
      shows that computer modules with case-based questions enhance learning in the
      short-term but at the expense of increased time and so decreased learning
      efficiency. This learning benefit was not maintained.

PMID- 22657940
TI  - Giant cell tumor of the distal ulna: a case report.
AB  - INTRODUCTION: Several cases of long bone giant cell tumor have been reported in
      the literature. We report the case of a patient with a giant cell tumor in the
      distal ulna. This is very unusual, with a reported incidence of 0.45 to 6%. CASE
      PRESENTATION: A 17-year-old Colombian man presented with a painful swelling of
      the left wrist. After performing an instrumental examination, a diagnosis of
      distal ulna giant cell tumor was made. The tumor was treated with an
      intralesional curettage, phenol application and bone grafting. CONCLUSIONS: This
      tumor may have a good prognosis if it is diagnosed early and radically treated.
      It is important to be aware of atypical cancer localizations in order to perform
      a proper diagnosis.

PMID- 22657942
TI  - Three-dimensional visualization of forming Hepatitis C virus-like particles by
      electron-tomography.
AB  - Hepatitis C virus infects almost 170 million people per year but its assembly
      pathway, architecture and the structures of its envelope proteins are poorly
      understood. Using electron tomography of plastic-embedded sections of insect
      cells, we have visualized the morphogenesis of recombinant Hepatitis C virus-like
      particles. Our data provide a three-dimensional sketch of viral assembly at the
      endoplasmic reticulum showing different budding stages and contiguity of buds.
      This latter phenomenon could play an important role during the assembly of wt-HCV
      and explain the size-heterogeneity of its particles.

PMID- 22657941
TI  - Medication adherence in older adults with cognitive impairment: a systematic
      evidence-based review.
AB  - BACKGROUND: Cognitive impairment challenges the ability to adhere to the complex
      medication regimens needed to treat multiple medical problems in older adults.
      OBJECTIVE: Our aim was to conduct a systematic evidence-based review to identify
      barriers to medication adherence in cognitively impaired older adults and
      interventions aimed at improving medication adherence. METHODS: A search of
      MEDLINE, EMBASE, PsycINFO, GoogleDocs, and CINAHL for articles published between
      1966 and February 29, 2012 was performed. Studies included older adults with a
      diagnosis of cognitive impairment of any degree (mild cognitive impairment or
      mild, moderate, or severe dementia). To identify barriers to adherence, we
      reviewed observational studies. To identify relevant interventions, we reviewed
      clinical trials targeting medication adherence in cognitively impaired older
      adults. We excluded studies lacking a measure of medication adherence or lacking
      an assessment of cognitive function, case reports or series, reviews, and those
      focusing on psychiatric disorders or infectious diseases. Population
      demographics, baseline cognitive function, medication adherence methods, barriers
      to adherence, and prospective intervention methodologies were extracted. RESULTS:
      The initial search identified 594 articles. Ten studies met inclusion criteria
      for barriers to adherence and three met inclusion criteria for interventional
      studies. Unique barriers to adherence included understanding new directions,
      living alone, scheduling medication administration into the daily routine, using
      potentially inappropriate medications, and uncooperative patients. Two studies
      evaluated reminder systems and showed no benefit in a small group of
      participants. One study improved adherence through telephone and televideo
      reminders at each dosing interval. The results of the review are limited by
      reviewing only published articles, missing barriers or interventions due to lack
      of subgroup analysis, study selection and extraction completed by 1 reviewer, and
      articles with at least an abstract published in English. CONCLUSIONS: The few
      studies identified limit the assessment of barriers to medication adherence in
      the cognitively impaired population. Successful interventions suggest that
      frequent human communication as reminder systems are more likely to improve
      adherence than nonhuman reminders.

PMID- 22657943
TI  - Stuttering, disability and the higher education sector in Australia.
AB  - The aim of this study was to ascertain the extent to which Australian public
      universities and their associated disability liaison services offer web-based
      information for current or prospective students who stutter. The disability pages
      of the websites of all 39 public universities in Australia were visited and the
      information about disability services assessed according to 12 criteria developed
      by the authors. Results indicate that there is a dearth of information on
      Australian university websites available for students or prospective students who
      stutter. Only 13% of the sites reported any form of alternative teaching and
      assessment procedures for speech-impaired students and only 51% of 39 disability
      liaison officers responded when contacted by email. Such a student could not make
      an informed choice to enrol in a university based upon the information on
      disability services available on public Australian university websites.

PMID- 22657948
TI  - Retroperitoneal schwannoma treated with percutaneous computed tomography-guided
      radiofrequency ablation.
AB  - Retroperitoneal schwannomas (RSs) are particularly rare tumors, and resection is
      the first choice for symptomatic patients. However, some RSs with anatomical
      complexities pose great challenges for surgeons attempting radical resection
      without sacrificing the nearby critical structures, and subtotal resection leads
      to local recurrence, especially in refractory malignant RSs. The authors have
      successfully applied percutaneous CT-guided radiofrequency ablation in 2 cases of
      RSs, with favorable long-term progression-free survival.

PMID- 22657947
TI  - High prevalence of heterotopic ossification after cervical disc arthroplasty:
      outcome and intraoperative findings following explantation of 22 cervical disc
      prostheses.
AB  - OBJECT: Cervical disc arthroplasty (CDA) has been increasingly used for the
      treatment of cervical disc herniations. However, the impact of CDA on adjacent
      segment degeneration and the degree of heterotopic ossification (HO) of the
      treated segment remain a subject of controversy. Due to a product failure of the
      Galileo-type disc prosthesis, 22 of these devices were explanted. The
      radiological and clinical course in each case was investigated in detail with an
      emphasis on the incidence of HO and facet joint degeneration 18 months following
      the operation. Intraoperative findings regarding ossification and implant
      fixation were documented. Thus, the authors were able to describe the true rate
      of adjacent-segment degeneration and HO following CDA and the clinical relevance
      thereof. METHODS: In all 22 patients, functional radiographic imaging was
      performed prior to surgery, 3 and 12 months after surgery, and prior to disc
      prosthesis explantation. At all time points, the range of motion (ROM) in the
      operated and adjacent segments was determined. A motion index was calculated
      using the preoperative and all postoperative ROMs (preoperative ROM/postoperative
      ROM). Computed tomography was used preoperatively to measure the height of the
      index segment, extent of HO, and the degree of the progression of facet
      arthrosis, and was used postoperatively prior to prosthesis explantation.
      Patients completed clinical questionnaires that included a visual analog scale
      and the Neck Disability Index. RESULTS: The motion index of the index segment
      declined gradually from 1.4 at 3 months postoperative to 1.2 prior to
      explantation, while the motion index of the adjacent upper segment increased from
      0.9 to 1.3. The mean ROM of the index segment was 10.4 degrees  +/- 6.7 degrees ,
      and fusion was observed in 2 (9%) of the 22 patients. Prosthesis migration was
      present in 3 patients (13.6%). Severe HO (Grades 3 and 4) was present in 17.4%.
      Computed tomography showed a significant increase of segmental height of the
      index segment (1.6 +/- 1.1 mm, p = 0.035), and a significant increase of left
      sided lateral osteophytes (1.7 +/- 2.1 mm, p = 0.009). The incidence of severe
      osteophyte formation (> 2 mm) occurred in 40%. Intraoperative findings reflected
      the results from CT, with primary lateral proliferation of osteophytes found in
      approximately 25% of patients. The mean visual analog scale scores were 3.8 +/-
      2.7 (neck) and 2.4 +/- 2.5 (arms), and the mean Neck Disability Index score was
      30 +/- 22. No correlation was found between radiological and clinical parameters.
      CONCLUSIONS: In this study, a higher incidence of HO after CDA could be
      demonstrated using CT, compared with studies using fluoroscopy only. However,
      patient selection and/or the operative technique might have contributed to the
      high prevalence of osteophyte formation. Thus, the exact indication for CDA has
      to be reconsidered. Because implant migration was detected, using fixation in the
      present CDA model appears suboptimal.

PMID- 22657949
TI  - Topical anesthesia for intravitreal injection.
AB  - In-office intravitreal delivery of medications has currently become the standard
      of care treatment for a variety of ocular conditions, including age-related
      macular degeneration, diabetic eye disease, cystoid macular edema, and vascular
      occlusions. Patients undergoing an intravitreal injection procedure most commonly
      experience pain at the injection site, which has led physicians to explore the
      best means to decrease or to abolish pain sensation. Currently, no method of
      topical anesthesia prior to intravitreal injection administration has been proven
      to eliminate pain completely. Comparisons between different topical anesthetic
      agents have not yielded a consensus superior agent to be widely recommended for
      regular use. In order to minimize pain and reduce anxiety, addressing the
      patient's injection-related concerns is important.

PMID- 22657951
TI  - A prospective study of predictors of relapse in anorexia nervosa: implications
      for relapse prevention.
AB  - Anorexia nervosa (AN) is a serious psychiatric disorder with a high rate of
      relapse. The goal of this study was to identify predictors of relapse in adult AN
      using a prospective, longitudinal design. Participants were 100 AN patients who
      had successfully completed specialized inpatient/day treatment, were weight
      restored to a body mass index (BMI) of at least 20 for a minimum of 2 weeks, and
      reported less than one binge-purge (BP) episode over the previous 28 days at the
      end of treatment. Predictor variables included baseline demographic and clinical
      features, behavioral and psychological changes during treatment, residual
      psychopathology at post-treatment, and motivation to recover. Results indicated
      that 41% of participants relapsed during the 1-year follow-up period. The highest
      risk period for relapse was between 4 and 9 months post-treatment. Predictors of
      relapse included: the BP subtype of AN, severity of checking behaviors at pre
      treatment, decrease in motivation to recover during treatment, and lower
      motivation to recover at post-treatment. These findings suggest that individuals
      with the BP subtype of AN are particularly susceptible to relapse. Increasing and
      maintaining motivation to recover during acute treatment may have an important
      impact on long-term outcome.

PMID- 22657950
TI  - A randomised, double-blind, placebo controlled cross-over study to determine the
      gastrointestinal effects of consumption of arabinoxylan-oligosaccharides enriched
      bread in healthy volunteers.
AB  - BACKGROUND: Prebiotics are food ingredients, usually non-digestible
      oligosaccharides, that are selectively fermented by populations of beneficial gut
      bacteria. Endoxylanases, altering the naturally present cereal arabinoxylans, are
      commonly used in the bread industry to improve dough and bread characteristics.
      Recently, an in situ method has been developed to produce arabinoxylan
      oligosaccharides (AXOS) at high levels in breads through the use of a
      thermophilic endoxylanase. AXOS have demonstrated potentially prebiotic
      properties in that they have been observed to lead to beneficial shifts in the
      microbiota in vitro and in murine, poultry and human studies. METHODS: A double
      blind, placebo controlled human intervention study was undertaken with 40 healthy
      adult volunteers to assess the impact of consumption of breads with in situ
      produced AXOS (containing 2.2 g AXOS) compared to non-endoxylanase treated
      breads. Volatile fatty acid concentrations in faeces were assessed and
      fluorescence in situ hybridisation was used to assess changes in gut microbial
      groups. Secretory immunoglobulin A (sIgA) levels in saliva were also measured.
      RESULTS: Consumption of AXOS-enriched breads led to increased faecal butyrate and
      a trend for reduced iso-valerate and fatty acids associated with protein
      fermentation. Faecal levels of bifidobacteria increased following initial control
      breads and remained elevated throughout the study. Lactobacilli levels were
      elevated following both placebo and AXOS-breads. No changes in salivary secretory
      IgA levels were observed during the study. Furthermore, no adverse effects on
      gastrointestinal symptoms were reported during AXOS-bread intake. CONCLUSIONS:
      AXOS-breads led to a potentially beneficial shift in fermentation end products
      and are well tolerated.

PMID- 22657952
TI  - Neurocognitive function in long-term treated schizophrenia: a five-year follow-up
      study.
AB  - Neurocognitive deficits are a core feature of schizophrenia. Deficits covering a
      wide range of functions have been well documented. However there is still a lack
      of longitudinal studies regarding the development of neurocognitive impairment.
      The current study examined the effect of time in long-term treated patients with
      schizophrenia and healthy controls on cognitive functions. A neurocognitive test
      battery was administered to 36 patients and 46 controls on two occasions with
      approximately 4.5 years interval. Patients performed significantly worse on all
      measures on both occasions. The only significant decline over time was the
      ability to shift mental set between different rules or categories (measured by
      Trail Making Test B). This decline was present in both patients and controls.
      Improvement on attention (tested by Continuous Performance Test) was found in
      patients only and improvement on verbal learning (tested by Rey Auditory Verbal
      Learning Test) was found only in controls. Education was significantly related to
      outcome in patients and age was related to outcome in controls. We conclude that
      neurocognitive function is relatively stable over 4.5 years in patients with long
      term treated schizophrenia, in line with previous scientific research. The
      authors discuss the impact of age and education and limitations of the study.

PMID- 22657953
TI  - The Beck depression inventory-II in adolescent mental health patients: cut-off
      scores for detecting depression and rating severity.
AB  - The Beck Depression Inventory-Second Edition (BDI-II) was developed as an
      indicator of the presence and severity of depression in psychiatric patients from
      age 13. Its cut-off scores were derived from an adult sample and differentiate
      four categories of severity but contain no screening cut-off score for
      classifying patients as depressed vs. nondepressed. We aimed to determine this
      screening cut-off score and to examine the utility of the severity cut-off scores
      for adolescents in mental health care. 88 adolescent psychiatric patients (13-16
      years, 58% female) completed the German BDI-II. A structured diagnostic interview
      served as the reference standard for computing receiver operating characteristic
      (ROC) curves and identified 24 adolescents (27%) as depressed. ROC analysis of
      depressed vs. nondepressed patients yielded an area under the curve (AUC) value
      of 0.93. The optimal screening cut-off score according to Youden's Index was
      >=23, where sensitivity was 0.88 and specificity was 0.92. The severity cut-off
      scores yielded satisfying sensitivity (>=0.89) and specificity (>=0.72) for mild
      and moderate but not for severe depression. Our findings indicate that the BDI-II
      can be recommended for screening for depressive disorders in adolescent mental
      health patients. However, the currently used severity cut-off scores may be
      suboptimal for this population.

PMID- 22657954
TI  - Sleep and dreaming in patients with borderline personality disorder: a
      polysomnographic study.
AB  - Previous research has demonstrated disturbances in sleep continuity in subjects
      with borderline personality disorders (BPD). Moreover, depression-like sleep
      abnormalities like reduced REM latency have been found in BPD subjects, even
      without comorbid major depression disorder. Yet it is still unknown what the
      effect is of co-morbid posttraumatic stress disorder on sleep continuity and
      dream content in BPD patients group. The present study compared 27 unmedicated
      female BPD subjects and healthy controls. The patients exhibited increased sleep
      fragmentation, increased REM density, and reduced REM latency. The findings were
      independent from co-morbid posttraumatic stress response (PTSD), which was
      present in 33% of the patient sample. Negatively toned dreams obtained by REM
      awakenings and nightmares were also reported more often by the patients-also
      irrespective of co-morbid PTSD-whereas dreams of specific BPD behavior, like self
      mutilation, were rare. Taking these finding into account, one might productively
      investigate whether the sleep abnormalities improve during successful treatment
      of BPD and whether efficient methods for treating nightmares can be beneficial
      for this patient group.

PMID- 22657955
TI  - Perkin-flmer corporation.

PMID- 22657956
TI  - Hitech advanced photo-oxidation, inc.

PMID- 22657957
TI  - Environmental chemistry comes of age.

PMID- 22657958
TI  - Now get all the product.

PMID- 22657960
TI  - Federal.

PMID- 22657959
TI  - International.

PMID- 22657961
TI  - Science.

PMID- 22657962
TI  - States.

PMID- 22657963
TI  - Awards.

PMID- 22657965
TI  - Business.

PMID- 22657964
TI  - Technology.

PMID- 22657966
TI  - Measurements.

PMID- 22657967
TI  - Clinton's 1995 environmental budget.

PMID- 22657968
TI  - Annual international conference & exhibition.

PMID- 22657969
TI  - Environmental chemistry of lakes and reservoirs.

PMID- 22657970
TI  - And the Detergent "Eco-label" Goes to...

PMID- 22657971
TI  - The use of ozonation to degrade organic contaminants in wastewaters.

PMID- 22657973
TI  - Barriers to technology adoption.

PMID- 22657974
TI  - The language of colloid and interface science.

PMID- 22657972
TI  - Aquatic risk assessment of polymers.

PMID- 22657976
TI  - Teaching general chemistry.

PMID- 22657975
TI  - Needed a national renewable energy strategy.

PMID- 22657977
TI  - The chemistry of the atmosphere: its impact on global change.

PMID- 22657978
TI  - Battelle.

PMID- 22657979
TI  - Hazardous waste.

PMID- 22657980
TI  - Air pollution.

PMID- 22657981
TI  - Instruments.

PMID- 22657982
TI  - Water treatment.

PMID- 22657983
TI  - Standards.

PMID- 22657984
TI  - Software.

PMID- 22657985
TI  - Services.

PMID- 22657986
TI  - Publications.

PMID- 22657987
TI  - Classified section.

PMID- 22657989
TI  - professional consulting services directory.

PMID- 22657991
TI  - Sport-specific biomechanics of spinal injuries in aesthetic athletes (dancers,
      gymnasts, and figure skaters).
AB  - Young aesthetic athletes require special understanding of the athletic
      biomechanical demands peculiar to each sport. The performance of these activities
      may impart specific biomechanical stresses and subsequent injury patterns. The
      clinician must understand these aspects as well as the spinal changes that occur
      with growth when many of these injuries often occur. Further, athletes, parents,
      coaches, and healthcare providers must be sensitive to the overall aspects of the
      athlete, including nutrition, overtraining, adequate recovery, proper technique,
      and limiting repetition of difficult maneuvers to minimize injuries.

PMID- 22657990
TI  - Sport-specific biomechanics of spinal injuries in the athlete (throwing athletes,
      rotational sports, and contact-collision sports).
AB  - Athletes consistently recruit or transfer high levels of repetitive force through
      the spine. Proper force transmission from the legs to the hips and pelvis and
      through the trunk is vital. Hip and pelvis joint restrictions and muscle strength
      deficits coupled with poor endurance of the trunk muscle will lead to spinal
      instability, which is habitually described in symptomatic athletes. A
      rehabilitation program that targets the unstable base first, and then progresses
      to strengthening of the pelvis and hips and targets control of movement in a
      sport-specific approach, should result in pain reduction, skill enhancement, and
      a safe return to play.

PMID- 22657992
TI  - Overview of spinal interventions.
AB  - Athletes represent a specific subgroup of highly motivated patients with a unique
      set of social and psychological incentives. Demands placed on the lumbosacral
      system are high, and athletes may be particularly prone to the pathology
      discussed above. For this reason, it is crucial to consider the athlete as a
      functional whole operating in concert with intrinsic and extrinsic factors and to
      consider the lumbosacral system within the context of the complete kinetic chain.
      Spinal interventions should never be considered in isolation but rather as part
      of a comprehensive rehabilitation program targeting psychosocial as well as
      biomechanical opportunities. When interventional procedures are warranted, they
      should be performed according to existing guidelines regarding indication,
      patient selection, and technique where possible and with systems in place to
      maximize patient safety and to consistently monitor for response. Each of the
      interventions discussed above should be performed with fluoroscopic guidance,
      given the lack of accuracy without fluoroscopy, and generally be reserved for
      athletes not responding to conservative care. When returning an athlete to play
      after ESI, we recommend careful serial evaluation as well as involvement of
      appropriate family members, athletic trainers, and coaches in the decision-making
      process. Athletes should not return to play with any significant objective
      neurologic deficits. In appropriate athletes, return to play should occur with
      graduated and comprehensive rehabilitation as discussed above. Because evidence
      concerning the interventions discussed in this article is often lacking, clinical
      judgment is paramount regarding their allocation. The interventions explored
      above likely do provide viable treatment adjuncts in the carefully selected
      athlete but are not without risk. Athlete safety and global well being should
      guide any decision to pursue interventional treatment options.

PMID- 22657993
TI  - Back pain in the pediatric and adolescent athlete.
AB  - Clinicians taking care of athletes are likely to see many young patients
      complaining of back pain. The young athlete places significant repetitive
      stresses across the growing thoracolumbar spine, which can cause acute and
      overuse injuries that are unique to this age and patient population. Fortunately,
      by using a careful and systematic approach, with a sport-specific history,
      careful physical exam, and proper imaging, most problems can be properly
      identified. Although it is important to always remember that rare and more
      serious problems such as a neoplasm or infection maybe a source of pain in the
      athletic patient, most problems are benign and can be treated conservatively.
      Accurate diagnosis and management of back pain not only can prevent long-term
      deformity and disability, but it can also allow young athletes to return to doing
      what they love to do most: play sports.

PMID- 22657994
TI  - Spinal deformity in young athletes.
AB  - Young athletes may have a spinal deformity incidentally or potentially related to
      their sport. These athletes should be encouraged to continue sports participation
      in many instances. Brace wear is commonly used for kyphotic and scoliosis
      deformities. Many sports can be played in the brace. Even with sports that cannot
      practically be played in the brace, most bracing protocols have enough time out
      of brace during the day for the athlete to continue participation. However, good
      physical therapy for flexibility and strengthening of the spine should be
      continued. Even sports that potentially aggravate the deformity may be continued
      in these circumstances.

PMID- 22657995
TI  - The young adult spine in sports.
AB  - In summary, LBP is a common problem for the young adult athlete, with discogenic
      pain being the most common of all etiologies. Although rare, more serious
      etiologies such as tumor or infection should be included in the differential
      diagnosis until effectively ruled out. Regardless of the cause, nonoperative and
      conservative strategies should be the cornerstone of treatment, owing to the
      favorable natural history of most LBP etiologies. Short-term non-narcotic
      medications are helpful, and avoidance of bed rest is critical for the athletic
      population. Rehabilitation should focus on stabilization and strengthening of the
      core and pelvic muscle groups, and biomechanical imbalances should be addressed.
      Surgical intervention ought to be utilized as a last resort in this population.
      Return to play should be considered only when the athlete is pain free with full
      range of motion and daily medications have been discontinued. Careful monitoring
      of the training regimen should always be undertaken,especially with chronic pain
      or recurrent injuries.

PMID- 22657996
TI  - The aging spine in sports.
AB  - 1. Masters athletes may experience low back pain from multiple sources. Masters
      athletes with discogenic back pain should avoid or modify sports with combined
      rotational and compressive forces; individuals with facet-mediated pain should
      avoid or modify sports with excessive extension and rotation. 2. Optimization of
      flexibility, strength, endurance, and core control is critical. Sports specific
      training, realistic goal setting, and counseling are of maximal importance. 3.
      Overall, the health benefits of continued sports and athletic participation
      outweigh the potential risks of spinal degeneration in middle-aged athletes.
      There is little correlation between radiographic appearance of the spine and
      symptoms; therefore, symptoms should serve as the primary guide when determining
      activity modifications. Overall, masters athletes should be encouraged to remain
      active and fit to enhance their quality of life and reduce the risk of
      cardiovascular disease.

PMID- 22657997
TI  - Lumbar spine surgery in athletes:: outcomes and return-to-play criteria.
AB  - Surgical treatment of lumbar spine conditions in athletes can produce excellent
      outcomes. Professional and competitive athletes participating in both noncontact
      and contact sports can return to their preinjury level of performance and have
      successful careers after lumbar discectomy for LDH. NFL players, especially
      offensive and defensive linemen, may experience greater improvement with lumbar
      discectomy than nonoperative treatment. Athletes who undergo direct pars repair
      for spondylolysis or grade I spondylolisthesis may be able to return to sports
      but their participation level may vary. Athletes and military personnel who
      undergo lumbar TDR are capable of returning to rigorous activities, including
      contact and extreme sports and unrestricted full-service military duty. Distal
      fusion level may be an independent negative predictor of successful RTP after
      posterior spinal fusion for adolescent idiopathic scoliosis. There is great
      variability in published RTP criteria, which are based primarily on authors'
      opinions and experience. Athletes must demonstrate resolution of preoperative
      symptoms, full range of motion, and successful completion of a structured
      rehabilitation program before returning to play. Physicians must ultimately base
      their decision to release an athlete back to sport on each individual's condition
      and on the chosen sport.

PMID- 22657998
TI  - Injuries and abnormalities of the cervical spine and return to play criteria.
AB  - Cervical spine injury has a wide spectrum of consequences for the contact
      athlete, ranging from minimal to catastrophic. Because of the potentially grave
      sequelae of cervical injury, it is incumbent on team physicians or treating spine
      surgeons to be knowledgeable of postinjury treatment and return-to-play
      algorithms. Sideline physicians must have a rehearsed, comprehensive protocol for
      ensuring rapid treatment should an on-field injury occur with contingency plans
      to transport an injured player to a medical facility if necessary. Likelihood of
      return to play is variable with the extent of injury, but high for stingers,
      relatively low for patients who suffer episodes of transient neuropraxia, and
      intermediate for players who undergo cervical fusion for disk herniation based on
      the best available evidence. However, patients must be evaluated carefully on a
      case-by-case basis because of the heterogeneity of injury severity and associated
      pathology.

PMID- 22657999
TI  - Degenerative disease of the cervical spine and its relationship to athletes.
AB  - Each sport presents with unique risk factors and different mechanisms of injury,
      and therefore extrapolation of the data from one sport to another makes
      comparison difficult. The current evidence exploring the relationship of athletes
      and degenerative changes of the cervical spine leaves much to be debated, and
      future prospective longitudinal studies will be needed to clarify our
      understanding further. Such research will help structure clinical recommendations
      and improve sports safety and the care of athletes of all ages. Currently, there
      is evidence to suggest that participation in collision sports is implicated in
      premature degeneration of the cervical spine. There is some evidence to suggest
      that the same is true with noncollision sports and activities that result in
      direct and indirect repetitive loads to the cervical spine over time. The risk
      factors have yet to be clearly identified. The natural history and sequelae of
      premature degeneration have yet to be elucidated. Cervical spondylosis also
      appears to increase the severity, but not the frequency, of irreversible
      neurologic injury during collision sport participation. Prudence dictates that we
      not ignore the present evidence suggesting a link between neuropraxia and
      cervical stenosis. Proper screening for cervical stenosis in patients with
      transient neuropraxia with subsequent cessation of participation in collision
      sports if severe stenosis is present is suggested. There is no consensus for RTP
      guidelines in the setting of transient neurologic injuries in the athlete when
      severe degeneration is present, and each case must be considered individually
      with regard to the sport involved.

PMID- 22658000
TI  - Spinal cord abnormalities in sports.
AB  - Many types of spinal abnormalities can have an impact on an athlete's ability to
      participate in sports. One of the challenges in the current era is distinguishing
      the clinically relevant lesions from the incidental. Almost without exception, a
      Chiarimal formation, significant syringomyelia or other cyst compressing the
      spinal cord or nerve roots, tethered spinal cord, or spinal tumor should prompt
      referral to a neurosurgeon. However, tonsillar ectopia (descent of the cerebellum
      less than 5 mm beyond the foramen magnum) and small dilatations of the central
      canal, are very commonly seen and appear to represent normal anatomic variants
      that place athletes at no increased risk of spinal injury, and should not be
      considered a contraindication to play. The recommendations made in this article
      are largely based on consensus and experience, but as we gain more clinical
      experience to correlate with the increasingly sophisticated imaging findings, we
      hope that these recommendations can be refined further.

PMID- 22658001
TI  - Infectious, inflammatory, and metabolic diseases affecting the athlete's spine.
AB  - Sports and weight-bearing activities can have a positive effect on bone health in
      the growing, mature, or aging athlete. However, certain athletic activities and
      training regimens may place the athlete at increased risk for stress fractures in
      the spine. In addition, some athletes have an underlying susceptibility to
      fracture due to either systemic or focal abnormalities. It is important to
      identify and treat these athletes in order to prevent stress fractures and reduce
      the risk of osteoporosis in late adulthood. Therefore, the pre-participation
      physical examination offers a unique opportunity to screen athletes for metabolic
      bone disease through the history and physical examination. Positive findings
      warrant a thorough workup including a metabolic bone laboratory panel, and
      possibly a DEXA scan, which includes a lateral spine view.

PMID- 22658002
TI  - Spinal tumors found in the athlete.
AB  - Spine tumors in the athlete are rare but should be included in the differential
      diagnosis of any patient in the adolescent or young adult age group with
      persistent or severe pain. Presenting symptoms are often nonspecific, so a high
      index of suspicion is needed to diagnose these lesions in a timely fashion. Early
      recognition and referral to an appropriate multidisciplinary spine tumor center
      can greatly improve prognosis for these challenging cases.

PMID- 22658003
TI  - Congratulations to Drs d'Hemecourt and Micheli-they've got our back.
      Introduction.

PMID- 22658004
TI  - The explosion in organized sports has resulted in a concomitant increase in
      sports injuries. Introduction.

PMID- 22658061
TI  - Evidence of silicene in honeycomb structures of silicon on Ag(111).
AB  - In the search for evidence of silicene, a two-dimensional honeycomb lattice of
      silicon, it is important to obtain a complete picture for the evolution of Si
      structures on Ag(111), which is believed to be the most suitable substrate for
      growth of silicene so far. In this work we report the finding and evolution of
      several monolayer superstructures of silicon on Ag(111), depending on the
      coverage and temperature. Combined with first-principles calculations, the
      detailed structures of these phases have been illuminated. These structures were
      found to share common building blocks of silicon rings, and they evolve from a
      fragment of silicene to a complete monolayer silicene and multilayer silicene.
      Our results elucidate how silicene forms on Ag(111) surface and provides methods
      to synthesize high-quality and large-scale silicene.

PMID- 22658062
TI  - Safety and efficacy of fractional bipolar radiofrequency treatment in Fitzpatrick
      skin types V-VI.
AB  - PURPOSE: To evaluate the safety and efficacy of a bipolar fractionated
      radiofrequency device for the improvement skin texture, fine lines and wrinkles
      in the treatment of skin types V through VI. DESIGN: Fifteen subjects, skin types
      V and VI, between the ages of 40 and 64 were enrolled. Each received three
      treatments to the full face with fractionated bipolar RF device (Syneron Inc.,
      Irvine, USA) spaced 30 days apart. Patients were evaluated by the study
      investigator and a blinded investigator at each treatment and 90 days after the
      last treatment for the treatment safety and efficacy. SUMMARY: A statistically
      significant improvement in wrinkles, texture and fine lines was noticed in most
      subjects. Any adverse events in particular post inflammatory hyperpigmentation or
      hypopigmentation were not seen in any of the patients. CONCLUSION: Our study
      suggests that the use of this fractionated radiofrequency device is a safe and
      effective method of skin rejuvenation for skin types V through VI.

PMID- 22658063
TI  - The role of nucleoside reverse transcriptase inhibitors usage in the incidence of
      hyperlactatemia and lactic acidosis in HIV/AIDS patients.
AB  - Hyperlactatemia and lactic acidosis (LA) are among the most dangerous and life
      threatening side effect that occurs during therapy with some nucleoside reverse
      transcriptase inhibitors (NRTIs), mainly didanosine (ddI) and stavudine (d4T),
      also known as d-drugs. Therefore, we performed a prospective, follow-up study and
      aimed to examine the incidence rates (IR) and rate ratios (RR) of hyperlactatemia
      and LA for each NRTI. Three hundred and ninety-six HIV-patients were included in
      final analysis comprising 783.8 person-years of follow-up. Between 1st January
      2000 and 1st January 2008, 19 cases of hyperlactatemia and 15 cases of LA were
      recorded. Between regimens with the significant impact for developing
      hyperlactatemia and LA the lowest IR was for didanosine (IR=2.87 per 100 person
      years, 95%CI=0.45-9.25 and IR=4.31 per 100 person-years, 95%CI=1.07-13.91,
      respectively), and the highest for didanosine+stavudine (IR=10.17 per 100 person
      years, 95%CI=1.02-19.76 and IR=7.39 per 100 person-years, 95%CI=1.02-13.05,
      respectively). Compared to didanosine alone the RR of hyperlactatemia was 2.67
      (95%CI=1.11-12.52) for stavudine, and 4.06 (95%CI=1.31-15.48) for
      didanosine+stavudine. The RR of LA was 3.12 (95%CI=1.13-10.65) for stavudine, and
      5.13 (95%CI=1.54-13.37) for didanosine+stavudine in comparison with didanosine
      alone. Other risk factors for AP were CD4 cell count less than 200 cells/mm3 and
      female sex. Our results suggest that the use of stavudine alone or in combination
      with didanosine should not be used as first-line therapy, especially in patients
      with CD4 cell count less than 200 cells/mm3 and females if other treatment
      options are available.

PMID- 22658064
TI  - Enhanced loading and controlled release of antibiotics using nucleic acids as an
      antibiotic-binding effector in hydrogels.
AB  - Antibiotic delivery is important to treat bacterial infections, one of the most
      challenging health problems globally. This study explored the application of
      nucleic acids as an antibiotic-binding effector for antibiotic loading and
      release. The data showed that the partition coefficient of tetracycline increased
      proportionally to the oligonucleotide concentration ranging from 0 to 1 mM.
      Resultantly, the incorporation of the oligonucleotides led to enhanced
      tetracycline loading in the hydrogels. In addition to the enhanced drug loading,
      the oligonucleotides could slow the release of tetracycline from the hydrogels.
      Experiments were further carried out to examine the capability of oligonucleotide
      functionalized hydrogels in the inhibition of bacterial growth. The results
      showed that the oligonucleotide-functionalized hydrogels had higher antibacterial
      efficiency. Moreover, after tetracycline release, the oligonucleotide
      functionalized hydrogels could be refilled with fresh tetracycline to reproduce
      the capability of inhibiting bacterial growth. Therefore, nucleic acid
      oligonucleotides are a promising antibiotic-binding effector for hydrogel
      functionalization in antibiotic delivery.

PMID- 22658066
TI  - Stent implantation in the native and recurrent aortic coarctation in children.

PMID- 22658067
TI  - They just don't get it: using digital stories to promote meaningful undergraduate
      reflection.

PMID- 22658068
TI  - The role of the teacher in remediating at-risk medical students.
AB  - BACKGROUND: Previous work identified complex ingredients of a remediation
      programme for at-risk medical students: mandatory, stable, facilitated small
      groups promote both cognitive and affective developments, with improved self
      regulation, metacognition and reflection resulting in significant performance
      gains. AIM: We explore the teachers' role in this intervention, aiming to expand
      and deepen understanding of remediation methods in medical education. METHODS:
      Extensive qualitative data from student surveys and in-depth teacher interviews,
      along with quantitative student performance data, produced a rich description of
      remediation processes. RESULTS: Remediation should support emotional needs and
      foster cognitive and metacognitive skills for self-regulation and critical
      thinking. Teachers of remediation need to motivate, critique, challenge and
      advise their learners, applying teaching and contextual expertise in a
      constructivist, student-centred environment that fosters curiosity and joy for
      learning. Teachers of remediation can mediate these processes through embodiment
      of five core roles: facilitator, nurturing mentor, disciplinarian, diagnostician
      and modeller of desired skills, attitudes and behaviours. CONCLUSION: Remediation
      of struggling medical students can be achieved through a cognitive apprenticeship
      within a small community of inquiry that motivates and challenges the students.
      This community needs teachers capable of performing a unique combination of roles
      that demands high levels of teaching presence and practical wisdom.

PMID- 22658069
TI  - A waste characterisation procedure for ADM1 implementation based on degradation
      kinetics.
AB  - In this study, a procedure accounting for degradation kinetics was developed to
      split the total COD of a substrate into each input state variable required for
      Anaerobic Digestion Model n degrees 1. The procedure is based on the combination
      of batch experimental degradation tests ("anaerobic respirometry") and numerical
      interpretation of the results obtained (optimisation of the ADM1 input state
      variable set). The effects of the main operating parameters, such as the
      substrate to inoculum ratio in batch experiments and the origin of the inoculum,
      were investigated. Combined with biochemical fractionation of the total COD of
      substrates, this method enabled determination of an ADM1-consistent input state
      variable set for each substrate with affordable identifiability. The substrate to
      inoculum ratio in the batch experiments and the origin of the inoculum influenced
      input state variables. However, based on results modelled for a CSTR fed with the
      substrate concerned, these effects were not significant. Indeed, if the optimal
      ranges of these operational parameters are respected, uncertainty in COD
      fractionation is mainly limited to temporal variability of the properties of the
      substrates. As the method is based on kinetics and is easy to implement for a
      wide range of substrates, it is a very promising way to numerically predict the
      effect of design parameters on the efficiency of an anaerobic CSTR. This method
      thus promotes the use of modelling for the design and optimisation of anaerobic
      processes.

PMID- 22658072
TI  - Erratum.

PMID- 22658074
TI  - The key role of repeated DNAs in sex chromosome evolution in two fish species
      with ZW sex chromosome system.
AB  - Despite substantial progress, there are still several gaps in our knowledge
      about the process of sex chromosome differentiation. The degeneration of sex
      specific chromosome in some species is well documented, but it is not clear if
      all species follow the same evolutionary pathway. The accumulation of repetitive
      DNA sequences, however, is a common feature. To better understand this
      involvement, fish species emerge as excellent models because they exhibit a wide
      variety of sex chromosome and sex determining systems. Besides, they have much
      younger sex chromosomes compared to higher vertebrates, making it possible to
      follow early steps of differentiation. Here, we analyzed the arrangement of 9
      repetitive DNA sequences in the W chromosomes of 2 fish species, namely Leporinus
      reinhardti and Triportheus auritus, which present well-differentiated ZZ/ZW sex
      system, but differ in respect to the size of the sex-specific chromosome. Both W
      chromosomes are almost fully heterochromatic, with accumulation of repeated DNAs
      in their heterochromatic regions. We found that microsatellites have strongly
      accumulated on the large W chromosome of L. reinhardti but not on the reduced
      size W chromosome of T. auritus and are therefore important players of the W
      chromosome expansion. The present data highlight that the evolution of the sex
      chromosomes can diverge even in the same type of sex system, with and without the
      degeneration of the specific-sex chromosome, being more dynamic than
      traditionally appreciated.

PMID- 22658075
TI  - Red meat in global nutrition.
AB  - The influence of data and recommendations from developed countries on nutrition
      guidance has overshadowed recognition of the key micronutrients and protein
      contributed by red meat to the global food supply. Relative to the energy it
      contributes, the impact of red meat on the nutritional quality of the human diet
      via its contribution of protein and key micronutrients is under-appreciated. The
      current discussion will review red meat nutrient composition and global
      consumption rates and discuss the evidence underpinning current dietary
      recommendations. The beneficial role of red meat in reducing risk factors
      associated with noncommunicable disease in developed countries and improving the
      nutritional status of developing nations will also be reviewed.

PMID- 22658076
TI  - Acquired brain injury self-management programme: a pilot study.
AB  - PRIMARY OBJECTIVE: Traditional rehabilitation is not well suited to individuals
      with chronic mild symptoms following an acquired brain injury. To address this,
      this study adapted a supported self-management programme (SMP) for this
      population. The aim of this study was to evaluate the potential effectiveness of
      this novel SMP. RESEARCH DESIGN: Retrospective case series with repeated
      measures. METHODS AND PROCEDURES: Fifty-three participants with chronic mild
      symptoms following an acquired brain injury (primarily mild traumatic brain
      injury) completed an SMP. The intervention involved eight coaching sessions with
      each an occupational therapist and psychologist, carried out in the community and
      based on SMP principles. The Canadian Occupational Performance Measure was
      administered at baseline, discharge and 3- and 9-month follow-up. This measure
      yielded scores for performance and satisfaction with daily functioning, covering
      the domains of self-care, productivity and leisure. MAIN OUTCOMES AND RESULTS: A
      complete case analysis of programme completers revealed that participants'
      ratings of their occupational performance and satisfaction improved markedly
      between baseline and discharge from the SMP. This set of outcome measures
      remained stable between discharge and the two follow-up points. CONCLUSIONS: This
      pilot study suggests that SMPs may improve daily functioning in individuals with
      chronic mild ABI symptoms. More methodologically robust clinical trials are
      warranted.

PMID- 22658077
TI  - Myoelectric stimulation on peroneal muscles resists simulated ankle sprain
      motion.
AB  - The inadequate reaction time of the peroneal muscles in response to an incorrect
      foot contact event has been proposed as one of the etiological factors
      contributing to ankle joint inversion injury. Thus, the current study aimed to
      investigate the efficacy of a myoelectric stimulation applied to the peroneal
      muscles in the prevention of a simulated ankle inversion trauma. Ten healthy male
      subjects performed simulated inversion and supination tests on a pair of
      mechanical sprain simulators. An electrical signal was delivered to the peroneal
      muscles of the subjects through a pair of electrode pads. The start of the
      stimulus was synchronized with the drop of the sprain simulator's platform. In
      order to determine the maximum delay time which the stimulus could still resist
      the simulated ankle sprain motion, different delay time were test (0, 5, 10, and
      15ms). Together with the control trial (no stimulus), there were 5 testing
      conditions for both simulated inversion and supination test. The effect was
      quantified by the drop in maximum ankle tilting angle and angular velocity, as
      determined by a motion analysis system with a standard laboratory procedure.
      Results showed that the myoelectric stimulation was effective in all conditions
      except the one with myoelectric stimulus delayed for 15ms in simulated supination
      test. It is concluded that myoelectric stimulation on peroneal muscles could
      resist an ankle spraining motion.

PMID- 22658078
TI  - Validity and reliability of shoulder kinematics in typically developing children
      and children with hemiplegic cerebral palsy.
AB  - Shoulder motion has been mainly analysed in children based on thoraco-humeral
      (TH) joint kinematics, excluding the scapula-thoracic (ST) and gleno-humeral (GH)
      joints. In order to measure 3D scapulo-humeral motion using an optoelectronic
      system, we propose a protocol based on an acromion marker cluster (AMC), a
      functional method to determine the gleno-humeral rotation centre and different
      Euler sequences. This study investigated the validity of the AMC compared to the
      palpation of anatomical landmarks with a scapula locator, assessed the intra
      session repeatability and the ability to discriminate differences of such a
      protocol in 10 typically developing children (TD) and 10 children with hemiplegic
      cerebral palsy (HCP) during 6 different tasks (flexion, abduction, horizontal
      abduction, hand to head, hand to controlateral shoulder and hand to back pocket).
      For both populations, the AMC method showed an overall Root Mean Square Error
      (RMSE) of 5.5 degrees . The AMC method under-estimated the protraction/retraction
      of the scapula during abduction. The within-session reliability was good to
      excellent for all tasks except the hand to back pocket task. The YXY recommended
      Euler sequence for TH and GH joints resulted in gimbal lock for most of the tasks
      whereas the XZY sequence could be used for most of the tasks and most of the
      children.

PMID- 22658079
TI  - Rescue of recombinant peste des petits ruminants virus: creation of a GFP
      expressing virus and application in rapid virus neutralization test.
AB  - Peste des petits ruminants virus (PPRV) causes high mortality in goats and sheep
      and the disease has shown a greatly increased geographic distribution over the
      last 15 years. It is responsible for serious socioeconomic problems in some of
      the poorest developing countries. The ability to create recombinant PPRV would
      provide a useful tool for investigating the biology of the virus and the
      pathology of disease, as well as for developing new vaccines and diagnostic
      methods. Here we report the first successful rescue of recombinant PPRV from a
      full-length cDNA clone of the virus genome. Successful recovery of PPRV was
      achieved by using a RNA polymerase II promoter to drive transcription of the full
      length virus antigenome. We have used this technique to construct a virus
      expressing a tracer protein (green fluorescent protein, GFP). The recombinant
      virus replicated as well as the parental virus and could stably express GFP
      during at least 10 passages. The newly established reverse genetics system for
      PPRV provides a novel method for constructing a vaccine using PPRV as a vector,
      and will also prove valuable for fundamental research on the biology of the
      virus. We found that our recombinant virus allowed more rapid and higher
      throughput assessment of PPRV neutralization antibody titer via the virus
      neutralization test (VNT) compared with the traditional method.

PMID- 22658080
TI  - Explicit maps to predict activation order in multiphase rhythms of a coupled cell
      network.
AB  - We present a novel extension of fast-slow analysis of clustered solutions to
      coupled networks of three cells, allowing for heterogeneity in the cells'
      intrinsic dynamics. In the model on which we focus, each cell is described by a
      pair of first-order differential equations, which are based on recent reduced
      neuronal network models for respiratory rhythmogenesis. Within each pair of
      equations, one dependent variable evolves on a fast time scale and one on a slow
      scale. The cells are coupled with inhibitory synapses that turn on and off on the
      fast time scale. In this context, we analyze solutions in which cells take turns
      activating, allowing any activation order, including multiple activations of two
      of the cells between successive activations of the third. Our analysis proceeds
      via the derivation of a set of explicit maps between the pairs of slow variables
      corresponding to the non-active cells on each cycle. We show how these maps can
      be used to determine the order in which cells will activate for a given initial
      condition and how evaluation of these maps on a few key curves in their domains
      can be used to constrain the possible activation orders that will be observed in
      network solutions. Moreover, under a small set of additional simplifying
      assumptions, we collapse the collection of maps into a single 2D map that can be
      computed explicitly. From this unified map, we analytically obtain boundary
      curves between all regions of initial conditions producing different activation
      patterns.

PMID- 22658081
TI  - Automated selected reaction monitoring software for accurate label-free protein
      quantification.
AB  - Selected reaction monitoring (SRM) is a mass spectrometry method with documented
      ability to quantify proteins accurately and reproducibly using labeled reference
      peptides. However, the use of labeled reference peptides becomes impractical if
      large numbers of peptides are targeted and when high flexibility is desired when
      selecting peptides. We have developed a label-free quantitative SRM workflow that
      relies on a new automated algorithm, Anubis, for accurate peak detection. Anubis
      efficiently removes interfering signals from contaminating peptides to estimate
      the true signal of the targeted peptides. We evaluated the algorithm on a
      published multisite data set and achieved results in line with manual data
      analysis. In complex peptide mixtures from whole proteome digests of
      Streptococcus pyogenes we achieved a technical variability across the entire
      proteome abundance range of 6.5-19.2%, which was considerably below the total
      variation across biological samples. Our results show that the label-free SRM
      workflow with automated data analysis is feasible for large-scale biological
      studies, opening up new possibilities for quantitative proteomics and systems
      biology.

PMID- 22658083
TI  - Synthesis and anti-breast cancer activity of new indolylquinone derivatives.
AB  - A series of novel indolylquinones have been synthesized by treating halogeno
      quinone with 2-substituated indole derivatives in the presence of kalium
      carbonate and TEBA in acetonitrile at room temperature. These compounds were
      evaluated for their antiproliferative activity against human MDA-MB-231 and MCF-7
      breast cancer cell lines. All the tested compounds showed potent mircomolar
      cytotoxicity activity in both breast cancer cell lines. 3d (IC(50) value=2.29
      MUg/mL for MCF-7 cells) and 3g (IC(50) value=3.99 MUg/mL for MDA-MB-231 cells)
      displayed the most potent antiproliferative activity of the series. Also, in
      vitro anticancer activity of the compounds further showed that bis
      indolylquinones were more active than mono-indolylquinones. Fluorescence
      microscopy analysis indicated that compound 3d and 3g inhibited breast cancer
      cells proliferation by triggering apoptotic cell death.

PMID- 22658082
TI  - Intra-coronary administration of tacrolimus markedly attenuates infarct size and
      preserves heart function in porcine myocardial infarction.
AB  - BACKGROUND: We test the hypothesis that intra-coronary tacrolimus administration
      can limit infarct size and preserve left ventricular ejection fraction (LVEF)
      after acute myocardial infarction (AMI) through ligating left anterior descending
      coronary artery (LAD) in mini-pigs. METHODS: Twelve male mini-pigs were
      randomized into AMI-saline (MI-only) group and AMI-tacrolimus (MI-Tac) group that
      received intra-coronary saline (3.0 mL) and tacrolimus (0.5 mg in 2.5 mL saline)
      injection, respectively, beyond site of ligation 30 minutes after LAD occlusion.
      RESULTS: Larger infarct area was noted in MI-only group (p < 0.001). Inflammatory
      biomarkers at protein [oxidative stress, tumor necrotic factor-alpha, nuclear
      factor-kappaB], gene (matrix metalloproteinase-9, plasminogen activator inhibitor
      1), and cellular (CD40+, CD68+ inflammatory cells) levels were remarkably higher
      in MI-only animals (p < 0.01). Conversely, anti-inflammatory biomarkers at gene
      level (Interleukin-10), gene and protein level (endothelial nitric oxide
      synthase), and anti-oxidant biomarkers at both gene and protein levels [heme
      oxygenase 1, NAD(P)H:quinone oxidoreductase] were lower in MI-only group (p <
      0.01). Number of apoptotic nuclei and apoptotic biomarkers expressions at gene
      and protein levels (Bax, caspase 3) were notably higher, whereas anti-apoptotic
      biomarkers at gene and protein levels (Bcl-2), LVEF, and fractional shortening
      were markedly lower in MI-only group (p < 0.001). CONCLUSION: Intra-coronary
      administration of tacrolimus significantly attenuated infarct size and preserved
      LV function.

PMID- 22658084
TI  - Novel polycyclic 'cage'-1,2-diamines as potential anti-tuberculosis agents.
AB  - A series of polycyclic 'cage' derivatives of N-geranyl-1,2 diamines were
      synthesized and screened for their anti-mycobacterial activity against H(37)Rv,
      multidrug resistant (MDR) and extensively drug-resistant (XDR) strains of
      tuberculosis. By substituting the adamantyl skeleton of SQ109 with
      trishomocubanyl (9), oxa-pentacycloundecyl (14, 16), pentacycloundecyl, PCU, (10,
      15) and azapentacycloundecyl (22, 23), the effect of other polycyclic "cage"
      skeletons could be investigated. Compound 9 (trishomocubanyl moiety) proved to be
      the most active (MICs: 0.5-2 MUg/mL) while PCU hydroxyl derivatives (15 and 23),
      oxa-pentacycloundecyl and azapentacycloundecyl derivatives displayed similar
      activity to SQ109 (MICs: 0.5-4 MUg/mL) against all three strains of TB used in
      this study.

PMID- 22658085
TI  - Synthesis and in vitro evaluation of novel tetrazole embedded 1,3,5
      trisubstituted pyrazoline derivatives as Entamoeba histolytica growth inhibitors.
AB  - A series of pyrazoline derivatives (1a-15a) was synthesized by cyclization of
      chalcones (1-15) with 2-[5-(4-methoxyphenyl)-1H-tetrazol-1-yl]acetohydrazide
      under basic conditions and were screened in vitro, to find out effect on the
      growth of HM1: IMSS strain of Entamoeba histolytica. The compounds 3a, 4a, 11a,
      13a and 14a showed encouraging results with IC(50) value in the range of 0.86
      1.28 MUM. However compound 13a showed most promising results with IC(50) = 0.86
      MUM which is half of the metronidazole, the standard drug used for protozoal
      infection. Cell viability test in human hepatocellular carcinoma cell line
      (HepG2) revealed non-toxic nature of new synthesized compounds. Safety index
      calculations prevailed compound 13a as highly antiamoebic and least cytotoxic
      (S.I. = >116.28), almost twice than metronidazole.

PMID- 22658086
TI  - Anatomical and histological characterization of ileal and jejunal Peyer's patch
      in lesser mouse deer (Tragulus javanicus).
AB  - Tragulidae is a primitive ungulate family within the order Cetartiodactyla,
      suborder Ruminantia. Domestic ruminants such as cattle, sheep, and goat have two
      types of Peyer's patches (PP): jejunal and ileal PP, in which there are
      morphological and functional differences. In this study, lesser mouse deer
      (Tragulus javanicus) PP was studied by gross anatomical and histological
      procedures. At the fetal stage, both types of PP were formed in the small
      intestine. Ileal PP was observed as a single continuous aggregation of lymphatic
      follicles extending cranially from the ileo-caecal junction. However, jejunal PP
      was observed as multiple and discrete accumulations of lymphatic follicles. This
      study showed that the lesser mouse deer has two types of PP in the small
      intestine. In addition, the anatomical and histological characteristics of
      jejunal and ileal PP are quite similar to those of other ruminants' jejunal and
      ileal PP. Further studies are needed to analyze immune function of both PP in
      lesser mouse deer in order to determine the evolutionary process of
      Cetartiodactyla.

PMID- 22658087
TI  - Pharmacogenomics-based RNA interference nanodelivery: focus on solid malignant
      tumors.
AB  - INTRODUCTION: RNA interference represents one of the most promising strategies in
      fighting disease. However, small RNA interference faces substantial challenges
      for in vivo application due to the inherent instability of the RNA interference
      molecule. Among the nonviral gene delivery carriers, nanoparticles have attracted
      interest due to their success in various model systems. Nanomaterials have unique
      properties compared to conventional bulk materials that may be applicable in this
      setting. The nanoparticle complex carrying small interference RNA can undergo
      surface modification to achieve targeted modification for tissue-specific
      delivery. However, toxicity issues of the delivery systems need to be addressed
      and they require a pharmacogenomic profile of their own. AREAS COVERED: The
      authors review pharmacogenomics, toxicogenomics, nanoparticle-based drug
      delivery, and small interference RNA, with a focus on how logically engineered
      nanoparticle delivery systems can be used for personalized medicine in malignant
      tumors. EXPERT OPINION: Pharmacogenomics may be helpful in addressing possible
      individualized drug response for both the gene silencing capability of the
      delivered siRNA and the nanoparticle drug delivery system as both complete and
      distinct units. This may be done by assessing variations in gene expressions and
      single nucleotide polymorphisms. Patient profiling may be key as patient
      noncompliance due to toxicity plays a major role in treatment failure.

PMID- 22658088
TI  - Ultrafast surface carrier dynamics in the topological insulator Bi2Te3.
AB  - We discuss the ultrafast evolution of the surface electronic structure of the
      topological insulator Bi(2)Te(3) following a femtosecond laser excitation. Using
      time and angle-resolved photoelectron spectroscopy, we provide a direct real-time
      visualization of the transient carrier population of both the surface states and
      the bulk conduction band. We find that the thermalization of the surface states
      is initially determined by interband scattering from the bulk conduction band,
      lasting for about 0.5 ps; subsequently, few picoseconds are necessary for the
      Dirac cone nonequilibrium electrons to recover a Fermi-Dirac distribution, while
      their relaxation extends over more than 10 ps. The surface sensitivity of our
      measurements makes it possible to estimate the range of the bulk-surface
      interband scattering channel, indicating that the process is effective over a
      distance of 5 nm or less. This establishes a correlation between the nanoscale
      thickness of the bulk charge reservoir and the evolution of the ultrafast carrier
      dynamics in the surface Dirac cone.

PMID- 22658089
TI  - J.T. Baker.

PMID- 22658090
TI  - Taking a stand on environmental policy.

PMID- 22658091
TI  - International.

PMID- 22658092
TI  - States.

PMID- 22658093
TI  - Federal.

PMID- 22658094
TI  - Science.

PMID- 22658095
TI  - Measurements.

PMID- 22658096
TI  - Technology.

PMID- 22658097
TI  - Business.

PMID- 22658098
TI  - Europe's Pollution Liability Debate Heats Up.

PMID- 22658100
TI  - Published BIMONTHLY by the American.

PMID- 22658099
TI  - PhotomicroncheMUistry of clouds, fogs, and aerosols.

PMID- 22658101
TI  - ES&T Information Express.

PMID- 22658102
TI  - AN INTRODUCTION TO Open-Path FT-IR Atmospheric Monitoring.

PMID- 22658103
TI  - In situ and on-site bioreclamation.

PMID- 22658104
TI  - Sessions will cover new developments.

PMID- 22658105
TI  - In the field of basic.

PMID- 22658106
TI  - Pittcon '94: what's new for environment analysis.

PMID- 22658107
TI  - LEARNING TO LIVE With LIFE CYCLE ASSESSMENT.

PMID- 22658108
TI  - Isotech inc.

PMID- 22658110
TI  - Acs publications.

PMID- 22658111
TI  - Air pollution.

PMID- 22658112
TI  - Clean energy.

PMID- 22658114
TI  - Instruments.

PMID- 22658113
TI  - Hazardous waste.

PMID- 22658115
TI  - Software.

PMID- 22658116
TI  - Standards.

PMID- 22658117
TI  - Water treatment.

PMID- 22658119
TI  - Services.

PMID- 22658118
TI  - Publications.

PMID- 22658120
TI  - Classified section.

PMID- 22658121
TI  - professional consulting services directory.

PMID- 22658123
TI  - A randomized double blind, vehicle controlled bilateral comparison study of the
      efficacy and safety of finasteride 0.5% solution in combination with intense
      pulsed light in the treatment of facial hirsutism.
AB  - OBJECTIVE: We sought to determine whether topical finasteride can enhance the
      efficacy of intense pulsed light hair removal. MATERIALS AND METHODS: An intense
      pulsed light (IPL) treatment with radiofrequency (RF) was performed every four
      weeks, resulting in up to three sessions, and again at the end of the study - 6
      months after the start of the experiment. Each patient also applied either
      finasteride or placebo solution twice daily to each side of the chin in a double
      blinded manner. RESULTS: A total of 77 patients were included in the study. Mean
      hair density before treatment in finasteride side of the patient's chin was 19.7
      +/- 11.7 and in placebo side was 19.1 +/- 11.3. After three sessions of IPL + RF
      treatment, combined with twice daily application of finasteride and placebo
      solutions, at the end of 6-month period mean hair density of 8 +/- 6.3 and 9 +/-
      5.6 was achieved in finasteride and placebo side respectively. Statistically
      significant difference was found between finasteride and placebo solution.
      CONCLUSIONS: We have demonstrated that the addition of finasteride solution to
      IPL + RF hair removal may result in a more reduction of unwanted facial hair in
      women when the combination is used for up to 6 months.

PMID- 22658124
TI  - Nonadherence to statin therapy: discontinuation after a single fill.
AB  - INTRODUCTION: Adherence to statin medications is known to be suboptimal. What is
      less known is the rate of discontinuation immediately after therapy has been
      initiated. The primary objective of this study was to determine what proportion
      of nonadherence in the first year of statin therapy was due to discontinuation
      after a single fill. METHODS: We identified new statin users within low-risk
      (hypertension [HTN]), medium-risk (coronary heart disease [CHD]), and high-risk
      (heart failure [HF]) cohorts during a 9-year period. All data came from
      administrative health care databases. RESULTS: The cohorts included 9445 HTN,
      1141 CHD, and 778 HF patients. At 1 year, the proportions of patients with less
      than 80% adherence to statin medications were 47.9% (HTN), 38.3% (CHD), and 50.0%
      (HF). Among all patients classified as nonadherent at 1 year, 18.0% of HTN, 16.3%
      of CHD, and 28.2% of HF patients had discontinued statin medications after only 1
      dispensation. Within 3 months of starting statin therapy, 29.7%, 40.3%, and 47.5%
      of all nonadherent HTN, CHD, and HF patients, respectively, had discontinued the
      new statin medication. After regression analysis, the only independent covariate
      that was consistently associated with discontinuation after a single fill was
      receiving fewer medical follow-up visits. CONCLUSIONS: Immediate discontinuation
      after a single fill contributes disproportionately to statin nonadherence. This
      suggests an important time to prevent nonadherence is within the first month of
      treatment initiation.

PMID- 22658125
TI  - Assignment of the absolute configuration of polyfunctional compounds by NMR using
      chiral derivatizing agents.

PMID- 22658126
TI  - Tumor immunotherapy directed at PD-1.

PMID- 22658127
TI  - Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
AB  - BACKGROUND: Blockade of programmed death 1 (PD-1), an inhibitory receptor
      expressed by T cells, can overcome immune resistance. We assessed the antitumor
      activity and safety of BMS-936558, an antibody that specifically blocks PD-1.
      METHODS: We enrolled patients with advanced melanoma, non-small-cell lung cancer,
      castration-resistant prostate cancer, or renal-cell or colorectal cancer to
      receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body
      weight every 2 weeks. Response was assessed after each 8-week treatment cycle.
      Patients received up to 12 cycles until disease progression or a complete
      response occurred. RESULTS: A total of 296 patients received treatment through
      February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of
      patients; there were three deaths from pulmonary toxicity. No maximum tolerated
      dose was defined. Adverse events consistent with immune-related causes were
      observed. Among 236 patients in whom response could be evaluated, objective
      responses (complete or partial responses) were observed in those with non-small
      cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all
      doses) were 18% among patients with non-small-cell lung cancer (14 of 76
      patients), 28% among patients with melanoma (26 of 94 patients), and 27% among
      patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of
      31 responses lasted 1 year or more in patients with 1 year or more of follow-up.
      To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the
      modulation of the PD-1-PD-L1 pathway, immunohistochemical analysis was performed
      on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD
      L1-negative tumors, none had an objective response; 9 of 25 patients (36%) with
      PD-L1-positive tumors had an objective response (P=0.006). CONCLUSIONS: Anti-PD-1
      antibody produced objective responses in approximately one in four to one in five
      patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the
      adverse-event profile does not appear to preclude its use. Preliminary data
      suggest a relationship between PD-L1 expression on tumor cells and objective
      response. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number,
      NCT00730639.).

PMID- 22658129
TI  - Tumor thrombus of inferior vena cava in patients with renal cell carcinoma -
      clinical and oncological outcome of 50 patients after surgery.
AB  - BACKGROUND: To evaluate oncological and clinical outcome in patients with renal
      cell carcinoma (RCC) and tumor thrombus involving inferior vena cava (IVC)
      treated with nephrectomy and thrombectomy. METHODS: We identified 50 patients
      with a median age of 65 years, who underwent radical surgical treatment for RCC
      and tumor thrombus of the IVC between 1997 and 2010. The charts were reviewed for
      pathological and surgical parameters, as well as complications and oncological
      outcome. RESULTS: The median follow-up was 26 months. In 21 patients (42%)
      distant metastases were already present at the time of surgery. All patients
      underwent radical nephrectomy, thrombectomy and lymph node dissection through a
      flank (15 patients/30%), thoracoabdominal (14 patients/28%) or midline abdominal
      approach (21 patients/42%), depending upon surgeon preference and upon the
      characteristics of tumor and associated thrombus. Extracorporal circulation with
      cardiopulmonary bypass (CPB) was performed in 10 patients (20%) with
      supradiaphragmal thrombus of IVC. Cancer-specific survival for the whole cohort
      at 5 years was 33.1%. Survival for the patients without distant metastasis at 5
      years was 50.7%, whereas survival rate in the metastatic group at 5 years was
      7.4%. Median survival of patients with metastatic disease was 16.4 months.On
      multivariate analysis lymph node invasion, distant metastasis and grading were
      independent prognostic factors. There was no statistically significant influence
      of level of the tumor thrombus on survival rate. Indeed, patients with
      supradiaphragmal tumor thrombus (n = 10) even had a better outcome (overall
      survival at 5 years of 58.33%) than the entire cohort. CONCLUSIONS: An aggressive
      surgical approach is the most effective therapeutic option in patients with RCC
      and any level of tumor thrombus and offers a reasonable longterm survival. Due to
      good clinical and oncological outcome we prefer the use of CPB with extracorporal
      circulation in patients with supradiaphragmal tumor thrombus. Cytoreductive
      surgery appears to be beneficial for patients with metastatic disease, especially
      when consecutive therapy is performed. Although sample size of our study cohort
      is limited consistent with some other studies lymph node invasion, distant
      metastasis and grading seem to have prognostic value.

PMID- 22658128
TI  - Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
AB  - BACKGROUND: Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor,
      and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells
      to evade the host's immune system. Blockade of interactions between PD-1 and PD
      L1 enhances immune function in vitro and mediates antitumor activity in
      preclinical models. METHODS: In this multicenter phase 1 trial, we administered
      intravenous anti-PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg
      per kilogram of body weight) to patients with selected advanced cancers. Anti-PD
      L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles
      or until the patient had a complete response or confirmed disease progression.
      RESULTS: As of February 24, 2012, a total of 207 patients--75 with non-small-cell
      lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell
      cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer,
      and 4 with breast cancer--had received anti-PD-L1 antibody. The median duration
      of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that
      investigators considered to be related to treatment occurred in 9% of patients.
      Among patients with a response that could be evaluated, an objective response (a
      complete or partial response) was observed in 9 of 52 patients with melanoma, 2
      of 17 with renal-cell cancer, 5 of 49 with non-small-cell lung cancer, and 1 of
      17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients
      with at least 1 year of follow-up. CONCLUSIONS: Antibody-mediated blockade of PD
      L1 induced durable tumor regression (objective response rate of 6 to 17%) and
      prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients
      with advanced cancers, including non-small-cell lung cancer, melanoma, and renal
      cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov
      number, NCT00729664.).

PMID- 22658130
TI  - Evaluation of osteopontin and CD44v6 expression in odontogenic cystic lesions by
      immunohistochemistry.
AB  - Odontogenic cysts are common lesions with different biological behavior.
      Odontogenic keratocysts (OKCs) and calcifying odontogenic cysts (COCs) with
      ameloblastoma-like epithelium are more aggressive than dentigerous cysts (DCs)
      and radicular cysts (RCs). Therefore, they were included in the list of
      odontogenic tumors by WHO. Osteopontin (OPN) is a calcium-binding glycoprotein
      present in many normal tissues. It plays a role in the migration and invasion of
      transformed epithelial cells. Binding of OPN to its receptor CD44v6 can enhance
      cell motility and migration. The purpose of this study was to compare the
      expression of these markers between odontogenic cysts of varying biological
      behavior. We examined OPN and CD44v6 expression in tissue sections of 14OKCs,
      14COCs, 14RCs and 14DCs by immunohistochemistry. OPN and CD44v6 immunostaining
      was observed in all lining epithelial cells of the studied lesions with different
      degrees. The highest level of OPN and CD44v6 expression was found in OKCs,
      followed by COCs, RCs and DCs. Comparison of both markers among four groups
      revealed significant differences (P<0.001). Our findings suggest that higher
      level of OPN and CD44v6 expression in epithelial cells of some lesions such as
      OKC and COC can explain the local aggressive behavior of them.

PMID- 22658131
TI  - Phylogeography and virulence structure of the powdery mildew population on its
      'new' host triticale.
AB  - BACKGROUND: Powdery mildew, caused by the obligate biotrophic fungus Blumeria
      graminis, is a major problem in cereal production as it can reduce quality and
      yield. B. graminis has evolved eight distinct formae speciales (f.sp.) which
      display strict host specialization. In the last decade, powdery mildew has
      emerged on triticale, the artificial intergeneric hybrid between wheat and rye.
      This emergence is probably triggered by a host range expansion of the wheat
      powdery mildew B. graminis f.sp. tritici. To gain more precise information about
      the evolutionary processes that led to this host range expansion, we pursued a
      combined pathological and genetic approach. RESULTS: B. graminis isolates were
      sampled from triticale, wheat and rye from different breeding regions in Europe.
      Pathogenicity tests showed that isolates collected from triticale are highly
      pathogenic on most of the tested triticale cultivars. Moreover, these isolates
      were also able to infect several wheat cultivars (their previous hosts), although
      a lower aggressiveness was observed compared to isolates collected from wheat.
      Phylogenetic analysis of nuclear gene regions identified two statistically
      significant clades, which to a certain extent correlated with pathogenicity. No
      differences in virulence profiles were found among the sampled regions, but the
      distribution of genetic variation demonstrated to be geography dependent. A
      multilocus haplotype network showed that haplotypes pathogenic on triticale are
      distributed at different sites in the network, but always clustered at or near
      the tips of the network. CONCLUSIONS: This study reveals a genetic structure in
      B. graminis with population differentiation according to geography and host
      specificity. In addition, evidence is brought forward demonstrating that the host
      range expansion of wheat isolates to the new host triticale occurred recently and
      multiple times at different locations in Europe.

PMID- 22658132
TI  - The communicating junctions, composition, structure and characteristics.

PMID- 22658133
TI  - Photolytic degradation of decabromodiphenyl ethane (DBDPE).
AB  - The photolytic degradation of decabromodiphenyl ethane (DBDPE), an alternative
      flame retardant to decabromodiphenyl ether, was investigated in a variety of
      matrixes (n-hexane, tetrahydrofuran, methanol/water, humic acid/water, and silica
      gel) by irradiation under ultraviolet light and in n-hexane under natural light.
      Photolytic degradation of DBDPE occurs in all the matrixes investigated within
      the irradiation period (<320 min). The degradation experiments showed varied
      reaction rates, dependent on the matrixes, with increasing half-lives (t(1/2)) in
      the order of tetrahydrofuran (t(1/2)=6.0 min)>n-hexane (t(1/2)=16.6 min)>humic
      acid/water (30<t(1/2)<60)>silica gel (t(1/2)=75.9 min)>methanol/water (t(1/2)>240
      min). The reaction in tetrahydrofuran, n-hexane, and silica gel matrixes can be
      described by the pseudo first order kinetics. Nevertheless, the matrixes have
      little effect on the degradation product distributions of DBDPE. A numbers of
      debrominated intermediates were identified. The degradation involves the initial
      formation of nona-BDPEs and the subsequent decomposition of these congeners to
      lower brominated congeners (octa- and hepta-BDPEs) within the irradiation time.
      To our knowledge, the present work is the first attempt to investigate the
      photolytic degradation kinetics and the identification of intermediates, as well
      as the degradation mechanism, during the degradation of DBDPE. Further research
      is needed to understand the photolytic degradation pattern of DBDPE in the
      natural environment.

PMID- 22658134
TI  - Analysis of iodinated haloacetic acids in drinking water by reversed-phase liquid
      chromatography/electrospray ionization/tandem mass spectrometry with large volume
      direct aqueous injection.
AB  - A large volume direct aqueous injection method was developed for the analysis of
      iodinated haloacetic acids in drinking water by using reversed-phase liquid
      chromatography/electrospray ionization/tandem mass spectrometry in the negative
      ion mode. Both the external and internal standard calibration methods were
      studied for the analysis of monoiodoacetic acid, chloroiodoacetic acid,
      bromoiodoacetic acid, and diiodoacetic acid in drinking water. The use of a
      divert valve technique for the mobile phase solvent delay, along with
      isotopically labeled analogs used as internal standards, effectively reduced and
      compensated for the ionization suppression typically caused by coexisting common
      inorganic anions. Under the optimized method conditions, the mean absolute and
      relative recoveries resulting from the replicate fortified deionized water and
      chlorinated drinking water analyses were 83-107% with a relative standard
      deviation of 0.7-11.7% and 84-111% with a relative standard deviation of 0.8
      12.1%, respectively. The method detection limits resulting from the external and
      internal standard calibrations, based on seven fortified deionized water
      replicates, were 0.7-2.3 ng/L and 0.5-1.9 ng/L, respectively.

PMID- 22658135
TI  - Preparative enantioseparations using supercritical fluid chromatography.
AB  - Chromatographic enantioseparation at the preparative scale is routinely used in
      pharmaceutical R&D to generate individual enantiomers. Supercritical fluid
      chromatography (SFC) has many advantages over liquid chromatography for these
      separations. These advantages include rapid screening of separation conditions at
      the analytical scale, more rapid preparative separations, higher purification
      throughputs, decreased solvent consumption and waste generation and higher
      product concentrations post separation. SFC is a green technique which utilizes
      significantly less solvent compared to HPLC and can often result in reduced
      purification costs.

PMID- 22658136
TI  - Peak capacity optimisation for high resolution peptide profiling in complex
      mixtures by liquid chromatography coupled to time-of-flight mass spectrometry:
      application to the Conus consors cone snail venom.
AB  - The high resolution profiling of complex mixtures is indispensable for obtaining
      online structural information on the highest possible number of the analytes
      present. This is particularly relevant for natural extracts, as for the venom of
      the predatory marine snail Conus consors, which contains numerous bioactive
      peptides with molecular masses ranging between 1000 and 5000 Da. The goal of the
      present work was to maximise peak capacity of peptides separations by LC-MS while
      maintaining a reasonable analysis time. The best gradient performance using the
      C. consors venom as a real sample was obtained with a mobile phase flow rate as
      high as possible to maximise performance in the gradient mode, and gradient time
      comprised between 75 and 350 min when using a 150 mm column length. The present
      study also confirmed that an elevated temperature (up to 90  degrees C) improves
      performance under ultra-high pressure liquid chromatography (UHPLC) conditions.
      However, the thermal stability of the analytes had to be critically evaluated.
      For the profiling of C. consors, analyte degradation was not clearly observable
      at 90  degrees C with analysis times of approximately 100 min. Finally, the MS
      source was found to cause significant additional band broadening in the UHPLC
      mode (sigma(ext)(2) was 10-24 times higher using TOF-MS vs. UV detection). Thus,
      if the MS contributes strongly to the peak capacity loss, classical 2.1mm I.D.
      columns can be replaced by 3.0mm I.D. to mitigate this problem. Based on these
      considerations, the optimal generic profiling conditions applied to the C.
      consors venom provided a peak capacity higher than 1100 for a gradient time of
      around 100 min, doubling the values reached by classical HPLC separation. UHPLC
      QTOF-MS/MS experiments carried out in these conditions provided exploitable data
      that matched with peptides present in the C. consors venom. These optimal LC
      conditions are thus compatible with online peptide deconvolution and matching
      against transcriptomic data and, to some extent, de novo sequencing in such
      complex mixtures.

PMID- 22658137
TI  - Minimisation of artefact formation of dimethyl disulphide during sampling and
      analysis of methanethiol in air using solid sorbent materials.
AB  - Methanethiol (MT) is a potent odorant that can be difficult to measure due to its
      high volatility and reactivity; it easily reacts to form dimethyl disulphide
      (DMDS) during sampling and/or analysis. This paper focuses on finding an optimal
      method for sampling and measuring MT with minimum artefact formation using
      sorbent materials and a thermal desorption-gas chromatography-mass spectrometry
      method (TD-GC-MS). Experiments were conducted to identify suitable sorbent
      materials and tubes for analysis. Breakthrough, desorption rate, the effects of
      storage and desorption temperatures were investigated and different drying
      methods were established with respect to quantitative sampling and formation of
      DMDS. Proton-transfer-reaction mass spectrometry (PTR-MS) was used in the
      development of the method and was an especially useful tool for determination of
      breakthrough. The results show that glass tubes packed with silica gel for pre
      concentration of MT before analysis with TD-GC-MS give the best results. In
      addition, a combination of Tenax TA and carbonised molecular sieve or Tenax TA
      cooled to <=0 degrees C gives acceptable results. 80 degrees C was found to be
      the optimal desorption temperature. For all the sampling methods tested, storage
      conditions were observed to be very critical for transformation of MT. Room
      temperature storage should be limited to few minutes and, in general, tubes
      should be kept at 0 degrees C or lower during storage.

PMID- 22658138
TI  - Development of a liquid chromatography tandem mass spectrometry method for trace
      analysis of trisiloxane surfactants in the aqueous environment: an alternative
      strategy for quantification of ethoxylated surfactants.
AB  - Trisiloxane surfactants, often referred to as superspreaders or superwetters, are
      added to pesticides to enhance the activity and the rainfastness of the active
      substance by promoting rapid spreading over hydrophobic surfaces. To fill the
      lack of data on the environmental occurrence of these compounds, we have
      developed and validated a method for their trace analysis in the aqueous
      environment. The method is based on liquid-liquid extraction followed by liquid
      chromatography and tandem mass spectrometry. The oligomeric distribution of
      trisiloxane surfactant in a reference solution was determined by a theoretical
      calculation and by experimental measurements. Based on these results, the
      quantification was performed by comparison with a calibration made with a single
      homologue instead of a mixture of homologues. This approach avoids a time
      consuming synthesis of pure homologues and reduces the risk of wrong estimation
      of the concentration because of different response factors of the sample and the
      standard. Such an approach could be applied to the quantification of other
      ethoxylated surfactants following a similar distribution. The validation was
      performed from 2 to 250 ng/L (total surfactant concentration) in deionized water,
      tap water, and river water (Rhine water). Knowing the oligomeric distribution of
      the polymer in the reference solution, the corresponding calibration ranges were
      estimated for individual homologues. Limits of quantification were found to be
      between 0.37 ng/L and 15 ng/L. The total recovery of sample preparation was
      between 77% and 116%. Matrix effects were lower than 10% with river water and the
      relative standard deviation evaluated over ten identical samples of spiked river
      water was below 12%.

PMID- 22658141
TI  - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics.

PMID- 22658144
TI  - Clinical use of genetic typing in human lipid disorders.

PMID- 22658145
TI  - Understanding Statin Use in America and Gaps in Patient Education (USAGE): an
      internet-based survey of 10,138 current and former statin users.
AB  - BACKGROUND: Statins substantially reduce the risk of cardiovascular disease and
      are generally well-tolerated. Despite this, many patients discontinue therapy. A
      better understanding of the characteristics of current and former statin users
      may be helpful for formulating strategies to improve long-term adherence.
      OBJECTIVE: The Understanding Statin Use in America and Gaps in Education (USAGE)
      survey assessed the attitudes, beliefs, practices, and behavior of current and
      former statin users. METHODS: Individuals 18 years or older who reported a
      history of high cholesterol and current or former statin use were identified
      within a registered consumer panel cohort in the United States and invited to
      participate in an Internet survey. RESULTS: Of the 10,138 respondents, 8918 (88%)
      were current statin users and 1220 (12%) were former users. Participants (mean
      age 61 years) were predominantly white (92%), female (61%), of middle income
      (median $44,504/yr), and had health insurance (93%). Among current users, 95%
      took a statin alone, and 70% had not missed a dose in the past month. Although
      ~70% reported that their physicians had explained the importance of cholesterol
      levels for their heart health former users were less satisfied with the
      discussions (65% vs. 83%, P < .05). Muscle-related side effects were reported by
      60% and 25% of former and current users, respectively (P < .05). Nearly half of
      all respondents switched statins at least once. The primary reason for switching
      by current users was cost (32%) and the primary reason for discontinuation was
      side effects (62%). CONCLUSIONS: This survey provides important insights into
      behavior and attitudes among current and former statin users and the results
      suggest that more effective dialogue between healthcare providers and patients
      may increase persistence of statin use, particularly when the patient has
      concerns about side effects and drug costs.

PMID- 22658146
TI  - Fatty acids in cardiovascular health and disease: a comprehensive update.
AB  - Research dating back to the 1950s reported an association between the consumption
      of saturated fatty acids (SFAs) and risk of coronary heart disease. Recent
      epidemiological evidence, however, challenges these findings. It is well accepted
      that the consumption of SFAs increases low-density lipoprotein cholesterol (LDL
      C), whereas carbohydrates, monounsaturated fatty acids (MUFAs), and
      polyunsaturated fatty acids (PUFAs) do not. High-density lipoprotein (HDL)-C
      increases with SFA intake. Among individuals who are insulin resistant, a low
      fat, high-carbohydrate diet typically has an adverse effect on lipid profiles (in
      addition to decreasing HDL-C, it also increases triglyceride and LDL particle
      concentrations). Consequently, a moderate fat diet in which unsaturated fatty
      acids replace SFAs and carbohydrates are not augmented is advised to lower LDL-C;
      compared with a low-fat diet, a moderate-fat diet will lower triglycerides and
      increase HDL-C. Now, there is some new evidence that is questioning the health
      benefits of even MUFAs and PUFAs. In addition, in a few recent studies
      investigators have also failed to demonstrate expected cardiovascular benefits of
      marine-derived omega-3 fatty acids. To clarify the clinical pros and cons of
      dietary fats, the National Lipid Association held a fatty acid symposium at the
      2011 National Lipid Association Scientific Sessions. During these sessions, the
      science regarding the effects of different fatty acid classes on coronary heart
      disease risk was reviewed.

PMID- 22658147
TI  - Effects of coadministered extended-release niacin/laropiprant and simvastatin on
      lipoprotein subclasses in patients with dyslipidemia.
AB  - BACKGROUND: The use of extended-release niacin and the prostaglandin D2 receptor
      antagonist laropiprant (ERN/LRPT) reduces niacin-induced flushing in patients
      while preserving its lipid-modifying effects. OBJECTIVE: This predefined
      exploratory analysis examined the individual and combined effects of ERN/LRPT and
      simvastatin (SIM) on lipoprotein subclasses. METHODS: This double-blind study
      randomized 1398 dyslipidemic patients equally to ERN/LRPT 1 g/20 mg, SIM (10, 20,
      or 40 mg), or ERN/LRPT 1 g/20 mg + SIM (10, 20, or 40 mg) once daily for 4 weeks.
      At week 5, doses were doubled, except SIM 40 mg (unchanged) and ERN/LRPT 1 g/20
      mg + SIM 40 mg (switched to ERN/LRPT 2 g/40 mg + SIM 40 mg). Cholesterol
      associated with lipoprotein subclasses was quantified by vertical auto profile II
      (VAP II). RESULTS: ERN/LRPT + SIM and SIM alone lowered LDL-C 1 and 3, whereas
      the effects were variable for ERN/LRPT; all three treatments increased LDL-C 4.
      ERN/LRPT + SIM and ERN/LRPT raised HDL-C 2 and 3, with greater relative percent
      changes in HDL 2 than HDL 3. ERN/LRPT + SIM for 12 weeks produced substantial
      reductions in IDL-C, which was additive compared with each monotherapy.
      CONCLUSION: Coadministered ERN/LRPT + SIM produced marked reductions in
      atherogenic lipoproteins, with the greatest effect on IDL-C, and increases in
      protective HDL subclasses.

PMID- 22658149
TI  - Editorial. Tissue engineering.

PMID- 22658148
TI  - Novel missense variants in LCAT and APOB genes in an Italian kindred with
      familial lecithin:cholesterol acyltransferase deficiency and
      hypobetalipoproteinemia.
AB  - BACKGROUND: Lecithin:cholesterol acyltransferase (LCAT) is responsible for
      cholesterol esterification in plasma. Mutations of LCAT gene cause familial LCAT
      deficiency, a metabolic disorder characterized by hypoalphalipoproteinemia.
      Apolipoprotein B (apoB) is the main protein component of very-low-density
      lipoproteins and low-density lipoprotein (LDL). Mutations of APOB gene cause
      familial hypobetalipoproteinemia, a codominant disorder characterized by low
      plasma levels of LDL cholesterol and apoB. OBJECTIVE: This was a genetic and
      biochemical analysis of an Italian kindred with hypobetalipoproteinemia whose
      proband presented with hypoalphalipoproteinemia and severe chronic kidney
      disease. METHODS: Plasma lipids and apolipoproteins, cholesterol esterification,
      and high-density lipoprotein (HDL) subclass distribution were analyzed. LCAT and
      APOB genes were sequenced. RESULTS: The proband had severe impairment of plasma
      cholesterol esterification and high prebeta-HDL content. He was heterozygote for
      the novel LCAT P406L variant, as were two other family members. The proband's
      wife and children presented with familial hypobetalipoproteinemia and were
      heterozygotes for the novel apoB H1401R variant. Cholesterol esterification rate
      of apoB H1401R carriers was reduced, likely attributable to the low amount of
      circulating LDL. After renal transplantation, proband's lipid profile, HDL
      subclass distribution, and plasma cholesterol esterification were almost at
      normal levels, suggesting a mild contribution of the LCAT P406L variant to his
      pretransplantation severe hypoalphalipoproteinemia and impairment of plasma
      cholesterol esterification. CONCLUSION: LCAT P406L variant had a mild effect on
      lipid profile, HDL subclass distribution, and plasma cholesterol esterification.
      ApoB H1401R variant was identified as possible cause of familial
      hypobetalipoproteinemia and resulted in a reduction of cholesterol esterification
      rate.

PMID- 22658150
TI  - Mechanical characterization and non-linear elastic modeling of poly(glycerol
      sebacate) for soft tissue engineering.
AB  - Scaffold tissue engineering strategies for repairing and replacing soft tissue
      aim to improve reconstructive and corrective surgical techniques whose
      limitations include suboptimal mechanical properties, fibrous capsule formation
      and volume loss due to graft resorption. An effective tissue engineering strategy
      requires a scaffolding material with low elastic modulus that behaves similarly
      to soft tissue, which has been characterized as a nonlinear elastic material. The
      material must also have the ability to be manufactured into specifically designed
      architectures. Poly(glycerol sebacate) (PGS) is a thermoset elastomer that meets
      these criteria. We hypothesize that the mechanical properties of PGS can be
      modulated through curing condition and architecture to produce materials with a
      range of stiffnesses. To evaluate this hypothesis, we manufactured PGS constructs
      cured under various conditions and having one of two architectures (solid or
      porous). Specimens were then tensile tested according to ASTM standards and the
      data were modeled using a nonlinear elastic Neo-Hookean model. Architecture and
      testing conditions, including elongation rate and wet versus dry conditions,
      affected the mechanical properties. Increasing curing time and temperature led to
      increased tangent modulus and decreased maximum strain for solid constructs.
      Porous constructs had lower nonlinear elastic properties, as did constructs of
      both architectures tested under simulated physiological conditions (wetted at 37 
      degrees C). Both solid and porous PGS specimens could be modeled well with the
      Neo-Hookean model. Future studies include comparing PGS properties to other
      biological tissue types and designing and characterizing PGS scaffolds for
      regenerating these tissues.

PMID- 22658151
TI  - Composite hydrogels for nucleus pulposus tissue engineering.
AB  - Tissue engineering offers a paradigm shift in the treatment of back pain.
      Engineered intervertebral discs could replace degenerated tissue and overcome the
      limitations of current treatments, which substantially alter the biomechanical
      properties of the spine. The centre of the disc, the nucleus pulposus, is an
      amorphous gel with a large bound water content and it can resist substantial
      compressive loads. Due to similarities in their compositions, hydrogels have
      frequently been considered as substitutes for the nucleus pulposus. However,
      there has been limited work characterising the time-dependent mechanical
      behaviour of hydrogel scaffolds for nucleus pulposus tissue engineering.
      Poroelastic behaviour, which plays a key role in nutrient transport, is of
      particular importance. Here, we investigate the time-dependent mechanical
      properties of gelatin and agar hydrogels and of gelatin-agar composites. The time
      dependent properties of these hydrogels are explored using viscoelastic and
      poroelastic frameworks. Several gel formulations demonstrate comparable
      equilibrium elastic behaviour to the nucleus pulposus under unconfined
      compression, but permeability values that are much greater than those of the
      native tissue. A range of time-dependent responses are observed in the composite
      gels examined, presenting the opportunity for targeted design of custom hydrogels
      with combinations of mechanical properties optimized for tissue engineering
      applications.

PMID- 22658152
TI  - The influence of collagen-glycosaminoglycan scaffold relative density and
      microstructural anisotropy on tenocyte bioactivity and transcriptomic stability.
AB  - Biomaterials for orthopedic tissue engineering must balance mechanical and
      bioactivity concerns. This work describes the fabrication of a homologous series
      of anisotropic collagen-GAG (CG) scaffolds with aligned tracks of ellipsoidal
      pores but increasing relative densities (rho(*)/rho(s)), and we report the role
      scaffold relative density plays in directing tenocyte bioactivity. Scaffold
      permeability and mechanical properties, both in tension and compression, were
      significantly influenced by relative density in a manner predicted by cellular
      solids models. Equine tenocytes showed greater levels of attachment, metabolic
      activity, soluble collagen synthesis, and alignment as well as less cell-mediated
      scaffold contraction in anisotropic CG scaffolds of increasing relative density.
      Notably, the lowest density scaffolds experienced significant cell-mediated
      contraction with associated decreases in tenocyte number as well as loss of
      microstructural integrity, aligned contact guidance cues, and preferential
      tenocyte orientation over a 14 day culture period. Gene expression analyses
      suggested tenocyte de-differentiation in the lowest density scaffold while
      indicating that the highest density scaffold supported significant increases in
      COMP (4-fold), tenascin-C (3-fold), and scleraxis (15-fold) expression as well as
      significant decreases in MMP-1 (9-fold) and MMP-13 (13-fold) expression on day
      14. These results suggest that anisotropic scaffold relative density can help to
      modulate the maintenance of a more tendon-like microenvironment and aid long-term
      tenocyte transcriptomic stability. Overall, this work demonstrates that relative
      density is a critical scaffold parameter, not only for insuring mechanical
      competence, but also for directing cell transcriptomic stability and behavior.

PMID- 22658153
TI  - Addition of hyaluronic acid improves cellular infiltration and promotes early
      stage chondrogenesis in a collagen-based scaffold for cartilage tissue
      engineering.
AB  - The response of mesenchymal stem cells (MSCs) to a matrix largely depends on the
      composition as well as the extrinsic mechanical and morphological properties of
      the substrate to which they adhere to. Collagen-glycosaminoglycan (CG) scaffolds
      have been extensively used in a range of tissue engineering applications with
      great success. This is due in part to the presence of the glycosaminoglycans
      (GAGs) in complementing the biofunctionality of collagen. In this context, the
      overall goal of this study was to investigate the effect of two GAG types:
      chondroitin sulphate (CS) and hyaluronic acid (HyA) on the mechanical and
      morphological characteristics of collagen-based scaffolds and subsequently on the
      differentiation of rat MSCs in vitro. Morphological characterisation revealed
      that the incorporation of HyA resulted in a significant reduction in scaffold
      mean pore size (93.9 MUm) relative to collagen-CS (CCS) scaffolds (136.2 MUm). In
      addition, the collagen-HyA (CHyA) scaffolds exhibited greater levels of MSC
      infiltration in comparison to the CCS scaffolds. Moreover, these CHyA scaffolds
      showed significant acceleration of early stage gene expression of SOX-9
      (approximately 60-fold higher, p<0.01) and collagen type II (approximately 35
      fold higher, p<0.01) as well as cartilage matrix production (7-fold higher sGAG
      content) in comparison to CCS scaffolds by day 14. Combining their ability to
      stimulate MSC migration and chondrogenesis in vitro, these CHyA scaffolds show
      great potential as appropriate matrices for promoting cartilage tissue repair.

PMID- 22658154
TI  - Mesenchymal stem cell fate is regulated by the composition and mechanical
      properties of collagen-glycosaminoglycan scaffolds.
AB  - In stem cell biology, focus has recently turned to the influence of the intrinsic
      properties of the extracellular matrix (ECM), such as structural, composition and
      elasticity, on stem cell differentiation. Utilising collagen-glycosaminoglycan
      (CG) scaffolds as an analogue of the ECM, this study set out to determine the
      effect of scaffold stiffness and composition on naive mesenchymal stem cell (MSC)
      differentiation in the absence of differentiation supplements. Dehydrothermal
      (DHT) and 1-ethyl-3-3-dimethyl aminopropyl carbodiimide (EDAC) crosslinking
      treatments were used to produce three homogeneous CG scaffolds with the same
      composition but different stiffness values: 0.5, 1 and 1.5 kPa. In addition, the
      effect of scaffold composition on MSC differentiation was investigated by
      utilising two glycosaminoglycan (GAG) types: chondroitin sulphate (CS) and
      hyaluronic acid (HyA). Results demonstrated that scaffolds with the lowest
      stiffness (0.5 kPa) facilitated a significant up-regulation in SOX9 expression
      indicating that MSCs are directed towards a chondrogenic lineage in more
      compliant scaffolds. In contrast, the greatest level of RUNX2 expression was
      found in the stiffest scaffolds (1.5 kPa) indicating that MSCs are directed
      towards an osteogenic lineage in stiffer scaffolds. Furthermore, results
      demonstrated that the level of up-regulation of SOX9 was higher within the CHyA
      scaffolds in comparison to the CCS scaffolds indicating that hyaluronic acid
      further influences chondrogenic differentiation. In contrast, enhanced RUNX2
      expression was observed in the CCS scaffolds in comparison to the CHyA scaffolds
      suggesting an osteogenic influence of chondroitin sulphate on MSC
      differentiation. In summary, this study demonstrates that, even in the absence of
      differentiation supplements, scaffold stiffness can direct the fate of MSCs, an
      effect that is further enhanced by the GAG type used within the CG scaffolds.
      These results have significant implications for the therapeutic uses of stem
      cells and enhance our understanding of the physical effects of the in vivo
      microenvironment on stem cell behaviour.

PMID- 22658155
TI  - Stiffening of human mesenchymal stem cell spheroid microenvironments induced by
      incorporation of gelatin microparticles.
AB  - Culturing multipotent adult mesenchymal stem cells as 3D aggregates augments
      their differentiation potential and paracrine activity. One caveat of stem cell
      spheroids, though, can be the limited diffusional transport barriers posed by the
      inherent 3D structure of the multicellular aggregates. In order to circumvent
      such limitations, polymeric microparticles have been incorporated into stem cell
      aggregates as a means to locally control the biochemical and physical properties
      of the 3D microenvironment. However, the introduction of biomaterials to the 3D
      stem cell microenvironment could alter the mechanical forces sensed by cells
      within aggregates, which in turn could impact various cell behaviors and overall
      spheroid mechanics. Therefore, the objective of this study was to determine the
      acute effects of biomaterial incorporation within mesenchymal stem cell spheroids
      on aggregate structure and mechanical properties. The results of this study
      demonstrate that although gelatin microparticle incorporation results in similar
      multi-cellular organization within human mesenchymal stem cell spheroids, the
      introduction of gelatin materials significantly impacts spheroid mechanical
      properties. The marked differences in spheroid mechanics induced by microparticle
      incorporation may hold major implications for in vitro directed differentiation
      strategies and offer a novel route to engineer the mechanical properties of
      tissue constructs ex vivo.

PMID- 22658156
TI  - Dynamic compressive strain influences chondrogenic gene expression in human
      periosteal cells: a case study.
AB  - Physical stimuli play a crucial role in skeletogenesis and osteochondral repair
      and regeneration. Although the periosteum and periosteum-derived cells offer
      considerable therapeutic potential, the molecular mechanisms that control their
      differentiation are still not fully understood. As an initial case study, this
      work explores the hypothesis that dynamic compression might selectively enhance
      chondrogenic and/or osteogenic differentiation in human periosteal cells from two
      donors. Donor derived human periosteal cells were expanded in monolayer culture
      before seeding in 3% (w/v) agarose constructs. The ability of this in vitro
      culture model to support cell viability, chondrogenesis, and mechanotransduction
      was optimised. The time course of early chondrogenic differentiation was assessed
      by real time RT-PCR of mRNA expression levels for bone and cartilage specific
      gene markers. Intermittent dynamic compression (1 Hz, 15% strain) was applied to
      constructs, in the presence or absence of 10 ng/ml TGF-beta3, for up to 4 days.
      The combined effect of TGF-beta3 and compressive loading on the expression levels
      of the Sox-9, Runx-2, ALP, Collagen X, and collagen type I genes was donor
      dependent. A synergistic effect was noted only in donor two, with peak mRNA
      expression levels at 24 h, particularly Sox-9 which increased 59.0-fold. These
      findings suggest that the interactions between mechanical stimuli and TGF-beta
      signalling may be an important mechanotransduction pathway for human periosteal
      cells and that, importantly, this cellular mechanosensitivity varies between
      donors.

PMID- 22658157
TI  - Cyclic tensile strain upon human mesenchymal stem cells in 2D and 3D culture
      differentially influences CCNL2, WDR61 and BAHCC1 gene expression levels.
AB  - It has been shown that tensile strain can alter cell behaviour. Evidence exists
      to confirm that human mesenchymal stem cells can be encouraged to differentiate
      in response to tensile loading forces. We have investigated the short-term
      effects of cyclic tensile strain (3%, 1 Hz) on gene expression in primary human
      mesenchymal stem cells in monolayer and whilst encapsulated in a self-assembled
      peptide hydrogel. The main aims of the project were to gain the following novel
      information: (1) to determine if the genes CCNL2, WDR61 and BAHCC1 are
      potentially important mechanosensitive genes in monolayer, (2) to determine if
      these genes showed the same differential expression in a 3D environment (either
      tethered to RGD or simply encapsulated within a hydrogel (with RGE motif)) and
      (3) to determine whether the mesenchymal stem cells would survive within the
      hydrogels over several days whilst enduring dynamic culture. In the monolayer
      system, real-time PCR confirmed CCNL2 was significantly downregulated after 1 h
      strain and 2 h latency (post strain). BAHCC1 was significantly downregulated
      after 1 h strain (both 2 h and 24 h latency). WDR61 followed the same trend in 2D
      culture. After 24 h strain and 2 h latency, BAHCC1 was significantly upregulated.
      We found that both types of peptide hydrogel supported viable mesenchymal stem
      cells over 48 h. Results of the 3D dynamic culture did not correspond with those
      of the 2D dynamic culture, where the BAHCC1 gene was not expressed in the 3D
      experiments. The disparity in the differential gene expression observed between
      the 2D and 3D culture systems may partly be a result of the different cellular
      environments in each. It is likely that cells cultured within an intricate 3D
      architecture respond to mechanical cues in a different and more complex manner
      than do cells in 2D monolayer, as is illustrated by our gene expression data.

PMID- 22658158
TI  - Transient exposure to TGF-beta3 improves the functional chondrogenesis of MSC
      laden hyaluronic acid hydrogels.
AB  - Tissue engineering with adult stem cells is a promising approach for the
      restoration of focal defects in articular cartilage. For this, progenitor cells
      would ideally be delivered to (and maintained within) the defect site via a
      biocompatible material and in combination with soluble factors to promote initial
      cell differentiation and subsequent tissue maturation in vivo. While growth
      factor delivery methods are continually being optimized, most offer only a short
      (days to weeks) delivery profile at high doses. To address this issue, we
      investigated mesenchymal stem cell (MSC) differentiation and maturation in
      photocrosslinkable hyaluronic acid (HA) hydrogels with transient exposure to the
      pro-chondrogenic molecule transforming growth factor-beta3 (TGF-beta3), at
      varying doses (10, 50 and 100 ng/mL) and durations (3, 7, 21 and 63 days).
      Mechanical, biochemical, and histological outcomes were evaluated through 9 weeks
      of culture. Results showed that a brief exposure (7 days) to a very high level
      (100 ng/mL) of TGF-beta3 was sufficient to both induce and maintain cartilage
      formation in these 3D constructs. Indeed, this short delivery resulted in
      constructs with mechanical and biochemical properties that exceeded that of
      continuous exposure to a lower level (10 ng/mL) of TGF-beta3 over the entire 9
      week time course. Of important note, the total TGF delivery in these two
      scenarios was roughly equivalent (200 vs. 180 ng), but the timing of delivery
      differed markedly. These data support the idea that acute exposure to a high dose
      of TGF will induce functional and long-term differentiation of stem cell
      populations, and further our efforts to improve cartilage repair in vivo.

PMID- 22658159
TI  - Expansion in the presence of FGF-2 enhances the functional development of
      cartilaginous tissues engineered using infrapatellar fat pad derived MSCs.
AB  - MSCs from non-cartilaginous knee joint tissues such as the infrapatellar fat pad
      (IFP) and synovium possess significant chondrogenic potential and provide a
      readily available and clinically feasible source of chondroprogenitor cells.
      Fibroblast growth factor-2 (FGF-2) has been shown to be a potent mitotic
      stimulator during ex vivo expansion of MSCs, as well as regulating their
      subsequent differentiation potential. The objective of this study was to
      investigate the longer term effects of FGF-2 expansion on the functional
      development of cartilaginous tissues engineered using MSCs derived from the IFP.
      IFP MSCs were isolated and expanded to passage 2 in a standard media formulation
      with or without FGF-2 (5 ng/ml) supplementation. Expanded cells were encapsulated
      in agarose hydrogels, maintained in chondrogenic media for 42 days and analysed
      to determine their mechanical properties and biochemical composition. Culture
      media, collected at each feed, was also analysed for biochemical constituents.
      MSCs expanded in the presence of FGF-2 proliferated more rapidly, with higher
      cell yields and lower population doubling times. FGF-2 expanded MSCs generated
      the most mechanically functional tissue. Matrix accumulation was dramatically
      higher after 21 days for FGF-2 expanded MSCs, but decreased between day 21 and
      42. By day 42, FGF-2 expanded MSCs had still accumulated ~1.4 fold higher sGAG
      and ~1.7 fold higher collagen compared to control groups. The total amount of
      sGAG synthesised (retained in hydrogels and released into the media) was ~2.4
      fold higher for FGF-2 expanded MSCs, with only ~25% of the total amount generated
      being retained within the constructs. Further studies are required to investigate
      whether IFP derived MSCs have a diminished capacity to synthesise other matrix
      components important in the aggregation, assembly and retention of proteoglycans.
      In conclusion, expanding MSCs in the presence of FGF-2 rapidly accelerates
      chondrogenesis in 3D agarose cultures resulting in superior mechanical
      functionality.

PMID- 22658160
TI  - Resveratrol effect on osteogenic differentiation of rat and human adipose derived
      stem cells in a 3-D culture environment.
AB  - The goal of this study was to investigate the effect of resveratrol treatment on
      the osteogenic potential of human and rat adipose derived stem cells in a 3-D
      culture environment. Adipose derived stem cells (ADSCs) have been widely studied
      and have shown promise as a potential source of osteogenic progenitor cells.
      Previous work had investigated the effect of 25 MUM resveratrol on the osteogenic
      differentiation of rat ADSCs in a 3-D environment and found that pre-treating
      cells for one passage prior to seeding on the scaffold yielded significantly more
      mineralization than untreated cells. We first sought to investigate whether this
      result was also observable with human ADSCs and found that the human cells did
      not respond to 25 MUM resveratrol in a positive manner suggesting a species
      specific difference in resveratrol dosage. Therefore, we next investigated
      multiple doses at or below 25 MUM resveratrol for both rat and human ADSCs. We
      found that doses below 25 MUM caused significantly more mineralization than 0
      (untreated) and 25 MUM treated cells in a 3-D culture environment. Further, we
      observed species differences in the total amount of mineralized matrix, as well
      as the mean mineral density suggesting that the nature of mineralization of the
      extracellular matrix was different between species. Histological examination of
      the scaffolds showed that the human cell constructs remain highly cellular in
      nature with small pockets of mineralization, while rat cell constructs showed
      much larger and more mature mineralized nodules. Taken together, we demonstrate
      dose dependent differences in the mineralization response of human and rat ADSCs
      to resveratrol treatment, suggesting that in vitro pre-conditioning of 3D adipose
      derived stem cell constructs may be an effective strategy to promote osteogenic
      differentiation prior to implantation.

PMID- 22658161
TI  - A silk hydrogel-based delivery system of bone morphogenetic protein for the
      treatment of large bone defects.
AB  - The use of tissue grafting for the repair of large bone defects has numerous
      limitations including donor site morbidity and the risk of disease transmission.
      These limitations have prompted research efforts to investigate the effects of
      combining biomaterial scaffolds with biochemical cues to augment bone repair. The
      goal of this study was to use a critically-sized rat femoral segmental defect
      model to investigate the efficacy of a delivery system consisting of an
      electrospun polycaprolactone (PCL) nanofiber mesh tube with a silk fibroin
      hydrogel for local recombinant bone morphogenetic protein 2 (BMP-2) delivery.
      Bilateral 8 mm segmental femoral defects were formed in 13-week-old Sprague
      Dawley rats. Perforated electrospun PCL nanofiber mesh tubes were fitted into the
      adjacent native bone such that the lumen of the tubes contained the defect
      (Kolambkar et al., 2011b). Silk hydrogels with or without BMP-2 were injected
      into the defect. Bone regeneration was longitudinally assessed using 2D X-ray
      radiography and 3D microcomputed topography (MUCT). Following sacrifice at 12
      weeks after surgery, the extracted femurs were either subjected to biomechanical
      testing or assigned for histology. The results demonstrated that silk was an
      effective carrier for BMP-2. Compared to the delivery system without BMP-2, the
      delivery system that contained BMP-2 resulted in more bone formation (p<0.05) at
      4, 8, 12 weeks after surgery. Biomechanical properties were also significantly
      improved in the presence of BMP-2 (p<0.05) and were comparable to age-matched
      intact femurs. Histological evaluation of the defect region indicated that the
      silk hydrogel has been completely degraded by the end of the study. Based on
      these results, we conclude that a BMP-2 delivery system consisting of an
      electrospun PCL nanofiber mesh tube with a silk hydrogel presents an effective
      strategy for functional repair of large bone defects.

PMID- 22658162
TI  - Differentiation potential of mesenchymal progenitor cells following
      transplantation into calvarial defects.
AB  - The complexity of stem cell lineage commitment requires studies to investigate
      the intrinsic and extrinsic regulatory events during differentiation. The
      objective of this long-term in vivo study was to investigate cellular
      differentiation and tissue formation of transplanted undifferentiated bone-marrow
      derived mesenchymal progenitor cells (BMPCs) in combination with a medical grade
      polycaprolactone (mPCL) scaffold and to compare them to osteoblasts; a more
      differentiated cell type in a calvarial defect model. Tissue formation was
      assessed via histology, mechanical and radiological methods after 3 12, and 24
      months. After 3 months our results indicated that transplanted mesenchymal
      progenitor cells were influenced by the niche of the host environment.
      Scaffold/BMPCs formed islands of bone tissue inside the defect area. However when
      the surrounding host calvarium contained a high content of fatty tissue, the fat
      content in the defect areas was also significantly higher. In contrast, defects
      repaired with scaffold/cOBs did not show this phenomenon. Analysis after 12 and
      24 months confirmed these observations indicating that a predominantly fatty
      environment leads to adipogenic development in the progenitor group.
      Biomechanical data revealed that the tissue was less firm in the BMPC group
      compared to the cOB seeded group. Evaluation of cell plasticity in vivo has
      important consequences in clinical cell transplantation protocols. This study
      indicates that cell fate decisions are partially regulated by extrinsic control
      mechanisms of the immediate environment suggesting that induction of BMPCs into a
      specific lineage could be beneficial prior transplantation.

PMID- 22658163
TI  - Managing heterogeneity in the study of neural oscillator dynamics.
AB  - We consider a coupled, heterogeneous population of relaxation oscillators used
      to model rhythmic oscillations in the pre-Botzinger complex. By choosing specific
      values of the parameter used to describe the heterogeneity, sampled from the
      probability distribution of the values of that parameter, we show how the effects
      of heterogeneity can be studied in a computationally efficient manner. When more
      than one parameter is heterogeneous, full or sparse tensor product grids are used
      to select appropriate parameter values. The method allows us to effectively
      reduce the dimensionality of the model, and it provides a means for
      systematically investigating the effects of heterogeneity in coupled systems,
      linking ideas from uncertainty quantification to those for the study of network
      dynamics.

PMID- 22658164
TI  - [Lymphocytopenia: aetiology and diagnosis, when to think about idiopathic CD4(+)
      lymphocytopenia?].
AB  - Lymphocytopenia is defined by a lymphocyte count less than 1500/mm(3) in adults
      and less than 4500/mm(3) in children before the age of 8 months. Lymphocytopenia
      can be global or selectively affect a peculiar lymphocyte subpopulation. The
      patient's age, the context as well as the associated clinical manifestations and
      treatment prescribed must be taken into account in order to identify the etiology
      of lymphocytopenia. In adults, lymphocytopenia can be caused by: (1) insufficient
      thymic output (primary immune deficiencies, corticosteroid treatment, zinc
      deficiency, etc.), (2) increased lymphocyte catabolism (radiotherapy,
      chemotherapy, immunosuppressant, HIV infection, systemic lupus, etc.), (3)
      modified lymphocyte distribution (viral infections, septic shock, extensive
      burns, splenomegaly, granulomatosis, etc.), (4) multifactorial or unknown
      etiology (end-stage renal disease, lymphoid malignancies, solid tumor, ethnicity,
      etc.). In children, in addition to these etiologies, other immune deficiencies
      may be responsible for severe lymphocytopenia (thymocytes apoptosis, cytokine
      deficiencies, altered B-cell and T-cell receptor synthesis, signal transduction
      and cellular interactions deficiencies). Idiopathic CD4(+) lymphocytopenia is a
      rare disorder. It is defined by a persisting lymphocyte CD4(+) count less or
      equal to 300/mm(3) or less or equal to 20% of total lymphocytes in the absence of
      alternative diagnosis. Clinical symptoms can be absent or include opportunistic
      infections, auto-immune manifestations, lymphoma or solid tumors. Treatment is
      similar to that of HIV-infected patients and sometimes relies on specific
      immunotherapy even though clinical benefit has not been evaluated.

PMID- 22658165
TI  - [Prevalence and diagnostic value of antinuclear antibodies without identified
      antigenic target: a retrospective study of 90 patients].
AB  - PURPOSE: The objective of this study was to determine the clinical relevance and
      the diagnostic significance of positive antinuclear antibodies (ANA) without
      identified antigenic target by the usual characterization technique. PATIENTS AND
      METHODS: Retrospective study conducted in the Laboratory of Immunology of Habib
      Bourguiba Hospital (Sfax, Tunisia) during 18 months. The inclusion criteria were
      the presence of an ANA titer greater or equal to 1/320 with negative
      characterization result. ANA screening was performed by indirect
      immunofluorescence (IIF) on Hep2 cells. Each positive serum was tested by IIF on
      Crithidia luciliae (anti-native DNA) and by immunodot (anti-nucleosome, anti
      histone, anti-Sm, anti-RNP, anti-SSA, anti-SSB, anti-Scl 70, anti-PM-Scl, anti
      Jo1, anti-PCNA and anti-ribosomal protein). Sera of systemic lupus erythematosus
      (SLE), myositis, and scleroderma patients were tested for anti-Ku, anti-PL7, anti
      PL12 and anti-Ro-52 using dot myositis. RESULTS: Sera of 90 patients were
      studied: 18 men and 72 women (average age: 44 years). Drug-induced ANA was found
      in eight patients. The most frequent clinical symptoms were joint (56.7%),
      cutaneous (54.4%) and constitutional symptoms (45.6%). The diagnosis of an
      autoimmune disease was suspected in 49 patients (54.5%) and confirmed in 30
      (33.3%) including 20 cases of connective tissue disease: myositis (n=6),
      scleroderma (n=5), Sjogren's syndrome (n=3), SLE (n=4), rheumatoid arthritis
      (n=6) and antiphospholipid syndrome (n=4). Other autoimmune diseases were less
      frequent. The anti-Ku antibody was detected in the majority of patients with
      connective tissue disease. The diagnosis of non-autoimmune diseases was
      established in 25.5% of patients. Eighteen patients (20%) had no diagnosis
      orientation. CONCLUSION: Our study demonstrated the diagnostic value of the
      presence of ANA even in the absence of known antigenic target, confirmed the role
      of the IIF as "gold standard" test for ANA screening, and suggested the
      usefulness of the addition of Ku antigen in the immunodot classic profile.

PMID- 22658166
TI  - [Acquired hemophilia A in prepartum: case report and literature review].
AB  - INTRODUCTION: Acquired hemophilia A (AH) is a rare hemorrhagic disorder,
      secondary to the occurrence of factor VIII inhibitor. In young patients, this
      disorder is commonly observed during the post-partum period, and has been rarely
      documented in the prepartum. We report a new case of a prepartum AH and review
      literature data. CASE REPORT: An isolated prolongation of the activated partial
      thromboplastin time (APTT) was fortuitously discovered in a 31-year-old pregnant
      women, with spontaneous ecchymosis of her lower limbs few days prior to delivery.
      Coagulation tests revealed decreased factor VIII activity (18%) and the presence
      of factor VIII inhibitor (1,4 Bethesda unit). In order to eradicate the
      autoantibody, the patient was first treated with prednisone and then with
      rituximab. CONCLUSION: Prepartum factor VIII inhibitors need to be precociously
      recognized to allow prophylactic management of the delivery bleeding.

PMID- 22658168
TI  - A comparison between blind and nerve stimulation guided obturator nerve block in
      transurethral resection of bladder tumor.
AB  - PURPOSE: To compare blind and nerve stimulation guided transurethral obturator
      nerve block (ONB) in transurethral resection of bladder tumor (TURBT) to prevent
      obturator reflex. PATIENTS AND METHODS: One hundred and twelve patients with
      lateral bladder wall tumors and at high risk for general anesthesia were
      categorized randomly in three groups. In the first group (34 patients), after
      spinal analgesia was administered, the exact site of the obturator nerve was
      determined by nerve stimulation and 15 mL of lidocaine HCl 2% was injected around
      the nerve. In the second group (31 patients), we determined the obturator nerve
      using nerve stimulation (like the first group), then 20 mL of saline was
      injected. In the third group (47 patients), the obturator nerve was determined
      based on anatomic landmarks and blocked subsequently. Leg jerking was reported
      and compared in the three groups. RESULTS: The median ages in the three groups
      were 55.4, 59.4, 57.8 years in the first, second, and third groups, respectively.
      Male/female ratios were 79.5% in the first, 80.7% in the second, and 80.9% in the
      third group (P=0.986). Leg jerking was reported in 5.8%, 34%, and 6.3% of
      patients in the first, second, and third groups, respectively (P=0.0001). ONB
      took 6.7 minutes in the first, 6.1 minutes in the second, and 5.2 minutes in the
      third group, on average. There was no report of adverse effects of lidocaine HCl
      in this study. CONCLUSION: Transvesical ONB is a safe and effective method of ONB
      before TURBT. This method is feasible by urologists and promising even without
      nerve stimulation and only by anatomic landmarks.

PMID- 22658169
TI  - Decreased expression of survivin, estrogen and progesterone receptors in
      endometrial tissues after radiofrequency treatment of dysfunctional uterine
      bleeding.
AB  - BACKGROUND: The purpose of the research is to study the histopathology and
      expression of survivin, estrogen and progesterone receptors (ER/PR) in the
      endometrium of patients with dysfunctional uterine bleeding (DUB) treated with
      radiofrequency endometrial ablation (REA). METHODS: A total of 98 DUB patients
      were enrolled in this case-control study. Among them, 66 underwent REA treatment
      and 32 optioned for hormone therapy as the control group. Immunohistochemical
      analysis for survivin, ER and PR expression was carried out on endometrial tissue
      samples collected before and 6 to 7  months after treatment for both groups.
      RESULTS: Both hormone and REA treatment ameliorated menstrual bleeding of DUB
      patients, with the latter showing a significantly higher effective rate.
      Endometrial surface tissue was replaced by fibrosis tissue in the REA treatment
      group. REA treatment also significantly reduced the expression of survivin, ER,
      and PR. Endometrial surface tissues collected from the hormone-treated control
      group neither showed any apparent morphological alteration nor in the expression
      of those receptors. CONCLUSIONS: REA treatment changed endometrial surface tissue
      type from gland rich to gland poor, and significantly decreased the expression of
      survivin, ER, and PR. This may be an important contributing mechanism for the
      long-term curative effect and prevention of DUB recurrence.

PMID- 22658170
TI  - Recessive congenital methemoglobinemia caused by a rare mechanism: maternal
      uniparental heterodisomy with segmental isodisomy of a chromosome 22.
AB  - Recessive congenital methemoglobinemia (RCM) is a very rare disorder caused by
      NADH-cytochrome b5 reductase (cb5r) deficiency. Two distinct clinical forms,
      types I and II, caused by cb5r deficiency have been recognized. In type I, the
      enzyme deficiency is restricted only to erythrocytes with cyanosis being the only
      major symptom. In contrast, in type II, the enzyme deficiency is generalized to
      all tissues and associated with neurological impairment, mental and growth
      retardation and reduced life expectancy, in addition to cyanosis. Recently, we
      conducted a study on an 11-year-old boy with cb5r deficiency type I. The
      mutational analysis of the CYB5R3 gene revealed that the boy is homozygous for
      L72P mutation. Surprisingly, his mother is heterozygous for this L72P mutant, but
      not his father. Thirteen microsatellite markers of chromosome 22 were selected to
      analyze the origins of the patient's chromosome 22. The result showed that both
      of the chromosome 22(s) of this patient came from the maternal side (uniparental
      heterodisomy of chromosome 22 with segmental isodisomy). This is the first case
      report of a patient with cb5r deficiency type I resulting from uniparental disomy
      and also discloses an alternate mechanism whereby this enzymatic disorder can be
      derived from a single parent.

PMID- 22658171
TI  - Environmental education.

PMID- 22658172
TI  - Ecology from space.

PMID- 22658173
TI  - International.

PMID- 22658174
TI  - Federal.

PMID- 22658175
TI  - Science.

PMID- 22658176
TI  - Awards.

PMID- 22658177
TI  - Technology.

PMID- 22658178
TI  - Measurements.

PMID- 22658179
TI  - Microwaves for detecting trace gases?

PMID- 22658181
TI  - Exporting environmental technologies.

PMID- 22658180
TI  - Business.

PMID- 22658182
TI  - Health of the north sea.

PMID- 22658184
TI  - ACS Software.

PMID- 22658183
TI  - Remote Sensing OF VEHICLE EXHAUST EMISSIONS.

PMID- 22658185
TI  - Classifieds/Advertisements.

PMID- 22658186
TI  - Remediating tar-contaminated soils at manufactured gas plant sites.

PMID- 22658188
TI  - A strategy for evaluating organic compounds in the aquatic environment.

PMID- 22658187
TI  - Acs publications.

PMID- 22658189
TI  - Acs publications.

PMID- 22658190
TI  - Electrochemical remediation takes to the field.

PMID- 22658191
TI  - Managing verification and validation costs.

PMID- 22658193
TI  - Es&T books.

PMID- 22658192
TI  - Acs publications.

PMID- 22658194
TI  - July 25-27, 1994 Norfolk, VA International Low-Level Waste Conference/Exhibit.

PMID- 22658196
TI  - Hazardous waste.

PMID- 22658195
TI  - Air pollution.

PMID- 22658197
TI  - Instruments.

PMID- 22658198
TI  - Publications.

PMID- 22658199
TI  - Services.

PMID- 22658200
TI  - Software.

PMID- 22658201
TI  - Standards.

PMID- 22658203
TI  - Classified section.

PMID- 22658202
TI  - Water treatment.

PMID- 22658205
TI  - services directory.

PMID- 22658206
TI  - The impact of a high-grade glioma on everyday life: a systematic review from the
      patient's and caregiver's perspective.
AB  - BACKGROUND: With poor prognosis and disabling symptomatology high-grade gliomas
      affect not only the patient but also the family. PURPOSE: The aim of this
      systematic review is to explore the experiences and needs of patients with a high
      grade glioma and their family caregivers. METHOD: Based on literature search in
      six databases, sixteen qualitative studies, published between 2000 and 2010 and
      with mixed methodological quality, were included. RESULTS: For both patients and
      their caregivers the diagnosis is marked by shock and recognition of death. For
      patients, coping with restriction seems to be most difficult to deal with.
      Especially loss of autonomy is hard. For caregivers, neurocognitive symptoms and
      personality changes irreversibly change the relationship with the patient leading
      to caregivers expressing a sense of total responsibility. The experience of being
      a caregiver is described by positive as well as negative feelings. Both patients
      and caregivers describe the need for hope, support and information. CONCLUSION:
      The review provides some relevant insight in the experiences and needs of
      patients with a high-grade glioma and their caregivers. The methodological
      limitations of the included studies, however, urge for more research to refine
      our understanding of patients' and caregivers' experiences and needs to better
      tune care to their needs.

PMID- 22658207
TI  - Combined use of fractional CO2 laser and radiofrequency waves to treat acne
      scars: a pilot study on 15 patients.
AB  - Fractional laser resurfacing has become an important technique in the management
      of a number of skin conditions, such as photoaging and scars. A variety of laser
      wavelengths and delivery systems have been introduced to improve immediate and
      long-term therapeutic results. The simultaneous emission of CO(2) laser and
      radiofrequency waves combines epidermal coagulation for a resurfacing effect and
      dermal denaturization for deeper remodelling. The authors present this new
      machine together with a preclinical histological study and pilot study on 15
      patients suffering from acne scars.

PMID- 22658208
TI  - Rotavirus-host cell interactions: an arms race.
AB  - As obligate parasites, viruses depend on the synthetic machinery of the cell to
      translate their proteins and on the cell's energy and building blocks to
      replicate their genomes. Cells respond to virus invasions by eliciting diverse
      responses to eliminate the incoming parasitic agents. In turn, to establish a
      successful infection, viruses have developed different strategies to take over
      the cellular metabolic machinery and to cope with the defense mechanisms of the
      cell. The characterization of this battle has allowed the discovery of the
      different elements that viruses and cells have developed in the attempt to
      overcome the enemy. Here some of the strategies used by rotaviruses to hijack the
      protein synthesis apparatus of the cell to ensure the translation of their mRNAs,
      and to deal with the cellular stress and antiviral responses will be reviewed.

PMID- 22658209
TI  - DFT and surface-enhanced Raman scattering study of tryptophan-silver complex.
AB  - Surface-enhanced Raman scattering (SERS) study of tryptophan was carried out in
      silver hydrosol. The surface adsorption properties of tryptophan were
      investigated due to its biological importance. Tryptophan is an essential amino
      acid needed for the normal growth in infants and for nitrogen balance in adults.
      DFT calculations using B3LYP functional with LANL2DZ basis set was carried out to
      support the experimental Raman and SERS data. The strong enhancement of 1343 cm(
      1) band, assigned to the CO(2) sym. stretching vibration in the SERS spectrum
      along with a red shift of 63 cm(-1), manifests that chemical mechanism
      contributes to the SERS activity. Moreover, the observed features in the SERS
      spectrum as well as theoretical calculations infer that tryptophan is chemisorbed
      to the silver surface directly through the oxygen and nitrogen atoms of the
      carboxylate and amino groups with an edge-on orientation with the indole ring
      lying nearly perpendicular to the silver surface. The SERS enhancement factors
      for various Raman vibrations of tryptophan were found to be of the order of 10(5)
      10(6).

PMID- 22658210
TI  - Deposition of composite coatings from particle-particle and particle-yeast blends
      by convective-sedimentation assembly.
AB  - The structures resulting from convective-sedimentation assembly (CSA) of bimodal
      suspensions (4.1-10% solids) of strongly charged sulfate latex microspheres (zeta
      potential -55.9+/-1.8 mV at pH 8.0) and weakly charged Saccharomyces cerevisiae
      (zeta potential -18.7+/-0.71 mV at pH 8.0) on glass, polyester, polypropylene,
      and aluminum foil substrates was evaluated. This study shows how substrate
      wettability, suspension composition, particle size ratio and surface charge
      affect the deposition process and resulting coating microstructure (particle
      ordering and void space). Size ratio and charge influence deposition, convective
      mixing or demixing and relative particle locations. Substrate wettability and
      suspension composition influence coating microstructure by controlling suspension
      delivery and spreading across the substrate. S. cerevisiae behave like negatively
      charged colloidal particles during CSA. CSA of particle-yeast blends result in
      open-packed structures (15-45% mean void space), instead of tightly packed
      coatings attainable with single component systems, confirming the existence of
      significant polymer particle-yeast interactions and formation of particle
      aggregates that disrupt coating microstructure during deposition. Further
      optimization of the process should allow void space reduction and deposition of
      cells plus adhesive polymer particles into tightly packed adhesive monolayer
      coatings for biosensors, biophotoabsorbers, energy applications, and highly
      reactive microbial absorbers.

PMID- 22658211
TI  - Immobilization of TiO2 nanoparticles in polymeric substrates by chemical bonding
      for multi-cycle photodegradation of organic pollutants.
AB  - Nano titanium dioxide (TiO(2)) photocatalyst is generally immobilized onto the
      matrix through the physical absorption, hydrogen bonding or chemical bonding,
      which is utilized for the application of wastewater treatment. In this research,
      TiO(2) nanoparticles were immobilized in polyvinyl alcohol (PVA) matrix via
      solution-casting combined with heat-treatment method. Structure characterization
      indicated that Ti-O-C chemical bond formed via dehydration reaction between
      TiO(2) and PVA during the heat treatment process, and TiO(2) nanoparticles had
      been chemically immobilized in PVA matrix. Photodegradation results of methyl
      orange (MO) showed that the film with 10 wt% TiO(2) and treated at 140 degrees C
      for 2h exhibited a remarkable ultraviolet (UV) photocatalytic activity,
      approximately close to the TiO(2) slurry system. This was mainly attributed to
      the fixation effect by Ti-O-C chemical bonds, which was indirectly confirmed by
      the slight loss of TiO(2) photocatalysts even after 25-cycle use. In addition,
      the good swelling ability of PVA matrix provided the MO molecules with more
      opportunities to fully contact with TiO(2), thus benefited the photocatalysis.
      This route to chemically immobilize TiO(2) nanoparticles is simple and cheap to
      prepare polymer/TiO(2) hybrid materials with high photocatalytic activity for
      multi-cycle use, which is of significance to the practical application of TiO(2)
      catalysts.

PMID- 22658212
TI  - Selected enzyme activities of urban heavy metal-polluted soils in the presence
      and absence of an oligochaete, Lampito mauritii (Kinberg).
AB  - Soils samples collected from five different areas (S1-S5) around electroplating
      industries in the city of Coimbatore were analysed for the activities of selected
      enzymes (cellulase, phosphatase, amylase, urease, and invertase) in the presence
      and absence of the earthworm Lampito mauritii (Kinberg). Heavy metal analysis of
      soils showed that chromium (<504 mg/kg) and copper (<28.1mg/kg) contents were
      much higher than cadmium (<10.60 mg/kg) except in S5, where cadmium (10.6 mg/kg)
      was higher than the copper. Except for phosphatase, the activities of all enzymes
      increased with increasing period of incubation under laboratory conditions, both
      with and without earthworms. The results of the three-way ANOVA (effect of three
      factors- worms-with and without addition, soil and incubation time), however,
      showed that there was no significant difference between enzyme activities (with
      and without earthworm) and soil and incubation time for amylase and urease
      activity. Further, no significant difference was found between soils for
      cellulase activity and between all the above factors for urease activity. The
      results concluded that though the earthworms died at the end of the incubation
      period, the resultant increase or decrease in the enzymatic activity may be
      attributed to the metabolic activities of the worms during their lifetime in the
      experimental container. Also, the worms after death may have provided suitable
      substrate for the growth of the microorganisms thereby influencing enzyme
      activity.

PMID- 22658213
TI  - First year nursing students' viewpoints about compromised clinical safety.
AB  - OBJECTIVE: Undergraduate nursing students must uphold patient safety as a
      professional and moral obligation across all clinical learning experiences. This
      expectation commences at entry into the nursing program. As part of a larger
      study exploring undergraduate baccalaureate nursing students' understanding of
      clinical safety, this paper specifically focuses on first year students'
      viewpoints about unsafe clinical learning situations. METHODS: Q-methodology was
      used. Sixty-eight first year nursing students participated in the ranking of 43
      statements indicative of unsafe clinical situations and practices. Data was
      entered into a Q-program for factor analysis. RESULTS: The results revealed a
      typology of four discrete viewpoints of unsafe clinical situations for first year
      students. These viewpoints included an overwhelming sense of inner discomfort,
      practicing contrary to conventions, lacking in professional integrity and
      disharmonizing relations. Overall, a consensus viewpoint described exonerating
      the clinical educator as not being solely responsible for clinical safety.
      DISCUSSION: This information may assist students and educators to cooperatively
      and purposefully construct a clinical learning milieu conducive to safety.

PMID- 22658214
TI  - [Meeting of multidisciplinary cooperation in all its forms: present and
      future...].

PMID- 22658215
TI  - Metabolic imaging biomarkers of postradiotherapy xerostomia.
AB  - PURPOSE: Xerostomia is a major complication of head and neck radiotherapy (RT).
      Available xerostomia measures remain flawed. [(18)F]fluorodeoxyglucose-labeled
      positron emission tomography-computed tomography (FDG-PET-CT) is routinely used
      for staging and response assessment of head and neck cancer. We investigated
      quantitative measurement of parotid gland FDG uptake as a potential biomarker for
      post-RT xerostomia. METHODS AND MATERIALS: Ninety-eight locally advanced head and
      neck cancer patients receiving definitive RT underwent baseline and post-RT FDG
      PET-CT on a prospective imaging trial. A separate validation cohort of 14
      patients underwent identical imaging while prospectively enrolled in a second
      trial collecting sialometry and patient-reported outcomes. Radiation dose and pre
      and post-RT standard uptake values (SUVs) for all voxels contained within
      parotid gland ROI were deformably registered. RESULTS: Average whole-gland or
      voxel-by-voxel models incorporating parotid D(Met) (defined as the pretreatment
      parotid SUV weighted by dose) accurately predicted posttreatment changes in
      parotid FDG uptake (e.g., fractional parotid SUV). Fractional loss of parotid FDG
      uptake closely paralleled early parotid toxicity defined by posttreatment
      salivary output (p < 0.01) and Radiation Therapy Oncology Group/European
      Organization for Research and Treatment of Cancer xerostomia scores (p < 0.01).
      CONCLUSIONS: In this pilot series, loss of parotid FDG uptake was strongly
      associated with acute clinical post-RT parotid toxicity. D(Met) may potentially
      be used to guide function-sparing treatment planning. Prospective validation of
      FDG-PET-CT as a convenient, quantifiable imaging biomarker of parotid function is
      warranted and ongoing.

PMID- 22658216
TI  - Inhibition of B-NHEJ in plateau-phase cells is not a direct consequence of
      suppressed growth factor signaling.
AB  - PURPOSE: It has long been known that the proliferation status of a cell is a
      determinant of radiation response, and the available evidence implicates repair
      of DNA double-strand breaks (DSBs) in the underlying mechanism. Recent results
      have shown that a novel, highly error-prone pathway of nonhomologous end joining
      (NHEJ) operating as backup (B-NHEJ) processes DSBs in irradiated cells when the
      canonical, DNA-PK (DNA-dependent protein kinase)-dependent pathway of NHEJ (D
      NHEJ) is compromised. Notably, B-NHEJ shows marked reduction in efficiency when D
      NHEJ-deficient cells cease to grow and enter a plateau phase. This phenomenon is
      widespread and observed in cells of different species with defects in core
      components of D-NHEJ, with the notable exception of DNA-PKcs (DNA-dependent
      protein kinase, catalytic subunit). Using new, standardized serum-deprivation
      protocols, we re-examine the growth requirements of B-NHEJ and test the role of
      epidermal growth factor receptor (EGFR) signaling in its regulation. METHODS AND
      MATERIALS: DSB repair was measured by pulsed-field gel electrophoresis in cells
      maintained under different conditions of growth. RESULTS: Serum deprivation in D
      NHEJ-deficient cells causes a rapid reduction in B-NHEJ similar to that measured
      in normally growing cells that enter the plateau phase of growth. Upon serum
      deprivation, reduction in B-NHEJ activity is evident at 4 h and reaches a plateau
      reflecting maximum inhibition at 12-16 h. The inhibition is reversible, and B
      NHEJ quickly recovers to the levels of actively growing cells upon supply of
      serum to serum-deprived cells. Chemical inhibition of EGFR in proliferating cells
      inhibits only marginally B-NHEJ and addition of EGFR in serum-deprived cells
      increases only a marginally B-NHEJ. CONCLUSIONS: The results document a rapid and
      fully reversible adaptation of B-NHEJ to growth activity and point to factors
      beyond EGFR in its regulation. They show notable differences in the regulation of
      error-prone DSB repair pathways between proliferating and non proliferating cells
      that may present new treatment design opportunities in radiation therapy.

PMID- 22658217
TI  - Bladder cancer patterns of pelvic failure: implications for adjuvant radiation
      therapy.
AB  - PURPOSE: Local-regional failures (LFs) after cystectomy with or without
      chemotherapy are common in locally advanced disease. Adjuvant radiation therapy
      (RT) could reduce LFs, but toxicity has discouraged its use. Modern RT techniques
      with improved normal tissue sparing have rekindled interest but require knowledge
      of pelvic failure patterns to design treatment volumes. METHODS AND MATERIALS:
      Five-year LF rates after radical cystectomy plus pelvic node dissection with or
      without chemotherapy were determined for 8 pelvic sites among 442 urothelial
      bladder carcinoma patients. The impact of pathologic stage, margin status, nodal
      involvement, and extent of node dissection on failure patterns was assessed using
      competing risk analysis. We calculated the percentage of patients whose sites of
      LF would have been completely encompassed within various hypothetical clinical
      target volumes (CTVs) for postoperative radiation. RESULTS: Compared with stage
      <=pT2, stage >=pT3 patients had higher 5-year LF rates in virtually all pelvic
      sites. Among stage >=pT3 patients, margin status significantly altered the
      failure pattern whereas extent of node dissection and nodal positivity did not.
      In stage >=pT3 patients with negative margins, failure occurred predominantly in
      the iliac/obturator nodes and uncommonly in the cystectomy bed and/or presacral
      nodes. Of these patients in whom failure subsequently occurred, 76% would have
      had all LF sites encompassed within CTVs covering only the iliac/obturator nodes.
      In stage >=pT3 with positive margins, cystectomy bed and/or presacral nodal
      failures increased significantly. Only 57% of such patients had all LF sites
      within CTVs limited to the iliac/obturator nodes, but including the cystectomy
      bed and presacral nodes in the CTV when margins were positive increased the
      percentage of LFs encompassed to 91%. CONCLUSIONS: Patterns of failure within the
      pelvis are summarized to facilitate design of adjuvant RT protocols. These data
      suggest that RT should target at least the iliac/obturator nodes in stage >=pT3
      with negative margins; coverage of the presacral nodes and cystectomy bed may be
      necessary for stage >=pT3 with positive margins.

PMID- 22658218
TI  - Intensity modulated radiation therapy dose painting for localized prostate cancer
      using 11C-choline positron emission tomography scans.
AB  - PURPOSE: To demonstrate the technical feasibility of intensity modulated
      radiation therapy (IMRT) dose painting using (11)C-choline positron emission
      tomography PET scans in patients with localized prostate cancer. METHODS AND
      MATERIALS: This was an RT planning study of 8 patients with prostate cancer who
      had (11)C-choline PET scans prior to radical prostatectomy. Two contours were
      semiautomatically generated on the basis of the PET scans for each patient: 60%
      and 70% of the maximum standardized uptake values (SUV(60%) and SUV(70%)). Three
      IMRT plans were generated for each patient: PLAN(78), which consisted of whole
      prostate radiation therapy to 78 Gy; PLAN(78-90), which consisted of whole
      prostate RT to 78 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to
      the SUV(70%) to 90 Gy; and PLAN(72-90), which consisted of whole-prostate RT to
      72 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to
      90 Gy. The feasibility of these plans was judged by their ability to reach
      prescription doses while adhering to published dose constraints. Tumor control
      probabilities based on PET scan-defined volumes (TCP(PET)) and on prostatectomy
      defined volumes (TCP(path)), and rectal normal tissue complication probabilities
      (NTCP) were compared between the plans. RESULTS: All plans for all patients
      reached prescription doses while adhering to dose constraints. TCP(PET) values
      for PLAN(78), PLAN(78-90), and PLAN(72-90) were 65%, 97%, and 96%, respectively.
      TCP(path) values were 71%, 97%, and 89%, respectively. Both PLAN(78-90) and
      PLAN(72-90) had significantly higher TCP(PET) (P=.002 and .001) and TCP(path)
      (P<.001 and .014) values than PLAN(78). PLAN(78-90) and PLAN(72-90) were not
      significantly different in terms of TCP(PET) or TCP(path). There were no
      significant differences in rectal NTCPs between the 3 plans. CONCLUSIONS: IMRT
      dose painting for localized prostate cancer using (11)C-choline PET scans is
      technically feasible. Dose painting results in higher TCPs without higher NTCPs.

PMID- 22658219
TI  - Megavoltage computed tomography image guidance with helical tomotherapy in
      patients with vertebral tumors: analysis of factors influencing interobserver
      variability.
AB  - PURPOSE: To evaluate megavoltage computed tomography (MVCT)-based image guidance
      with helical tomotherapy in patients with vertebral tumors by analyzing factors
      influencing interobserver variability, considered as quality criterion of image
      guidance. METHODS AND MATERIALS: Five radiation oncologists retrospectively
      registered 103 MVCTs in 10 patients to planning kilovoltage CTs by rigid
      transformations in 4 df. Interobserver variabilities were quantified using the
      standard deviations (SDs) of the distributions of the correction vector
      components about the observers' fraction mean. To assess intraobserver
      variabilities, registrations were repeated after >=4 weeks. Residual deviations
      after setup correction due to uncorrectable rotational errors and elastic
      deformations were determined at 3 craniocaudal target positions. To differentiate
      observer-related variations in minimizing these residual deviations across the 3
      dimensional MVCT from image resolution effects, 2-dimensional registrations were
      performed in 30 single transverse and sagittal MVCT slices. Axial and
      longitudinal MVCT image resolutions were quantified. For comparison, image
      resolution of kilovoltage cone-beam CTs (CBCTs) and interobserver variability in
      registrations of 43 CBCTs were determined. RESULTS: Axial MVCT image resolution
      is 3.9 lp/cm. Longitudinal MVCT resolution amounts to 6.3 mm, assessed as full
      width at half-maximum of thin objects in MVCTs with finest pitch. Longitudinal
      CBCT resolution is better (full-width at half-maximum, 2.5 mm for CBCTs with 1-mm
      slices). In MVCT registrations, interobserver variability in the craniocaudal
      direction (SD 1.23 mm) is significantly larger than in the lateral and
      ventrodorsal directions (SD 0.84 and 0.91 mm, respectively) and significantly
      larger compared with CBCT alignments (SD 1.04 mm). Intraobserver variabilities
      are significantly smaller than corresponding interobserver variabilities
      (variance ratio [VR] 1.8-3.1). Compared with 3-dimensional registrations, 2
      dimensional registrations have significantly smaller interobserver variability in
      the lateral and ventrodorsal directions (VR 3.8 and 2.8, respectively) but not in
      the craniocaudal direction (VR 0.75). CONCLUSION: Tomotherapy image guidance
      precision is affected by image resolution and residual deviations after setup
      correction. Eliminating the effect of residual deviations yields small
      interobserver variabilities with submillimeter precision in the axial plane. In
      contrast, interobserver variability in the craniocaudal direction is dominated by
      the poorer longitudinal MVCT image resolution. Residual deviations after image
      guidance exist and need to be considered when dose gradients ultimately
      achievable with image guided radiation therapy techniques are analyzed.

PMID- 22658220
TI  - Exogenous treatment with salicylic acid attenuates occurrence of citrus canker in
      susceptible navel orange (Citrus sinensis Osbeck).
AB  - Citrus canker caused by Xanthomonas axonopodis pv. citri (Xac) is a devastating
      bacterial disease threatening the citrus industry. Salicylic acid (SA) plays a
      key role in plant defense response to biotic stress, but information is scarce
      concerning the application of SA to enhancing Xac resistance. In the present
      research attempts were made to investigate how exogenous application of SA
      influenced canker disease outbreak in navel orange (Citrus sinensis). Exogenously
      applied SA at 0.25 mM significantly enhanced the endogenous free and bound SA,
      particularly the latter. Upon exposure to Xac, lower disease incidence rate and
      smaller lesion sites were observed in the samples pre-treated with SA,
      accompanied by repression of bacterial growth at the lesion sites. Concurrent
      with the augmented disease resistance, SA-treated leaves had higher H2O2 level
      and smaller stomata apertures before or after Xac infection when compared with
      their counterparts pre-treated with water (control). SA treatment elevated the
      activities of phenylalanine ammonia-lyase and beta-1,3-glucanase, but only the
      latter was higher in the SA-treated samples after Xac infection. In addition,
      mRNA levels of two pathogenesis-related genes, CsCHI and CsPR4A, were higher in
      the SA-treated samples relative to the control. Taken together, our results
      strongly suggest that the exogenously applied SA has evoked a cascade of
      physiological and molecular events that function singly or in concert to confer
      resistance to Xac invasion.

PMID- 22658221
TI  - Mannans in tomato fruit are not depolymerized during ripening despite the
      presence of endo-beta-mannanase.
AB  - Cell walls of tomato fruit contain hemicellulosic mannans that may fulfill a
      structural role. Two populations were purified from cell walls of red ripe tomato
      tissue and named galactoglucomannan-glucuronoxylan I and II (GGM-GX I and II),
      respectively. Both polysaccharides not only consisted of mannose, glucose and
      galactose, indicating the presence of GGM, but also contained xylose and
      glucuronic acid, indicating the presence of GX. Treatment of both polysaccharides
      with xylanase or endo-beta-mannanase showed that the GX and the GGM were
      associated in a complex. The composition of GGM-GX II changed slightly during
      tomato ripening, but both GGM-GX I and II showed no change in molecular weight,
      indicating that they were not hydrolyzed during ripening. Ripe tomato fruit also
      possess an endo-beta-mannanase, an enzyme that in vitro was capable of either
      hydrolyzing GGM-GX I and II (endo-beta-mannanase activity), or transglycosylating
      them in the presence of mannan oligosaccharides (mannan transglycosylase
      activity). The lack of evidence for hydrolysis of these potential substrates in
      vivo suggests either that the enzyme and potential substrates are not accessible
      to each other for some reason, or that the main activity of endo-beta-mannanase
      is not hydrolysis but transglycosylation, a reaction in which polysaccharide
      substrates and end-products are indistinguishable. Transglycosylation would
      remodel rather than weaken the cell wall and allow the fruit epidermis to
      possibly retain flexibility and plasticity to resist cracking and infection when
      the fruit is ripe.

PMID- 22658222
TI  - The jasmonate receptor COI1 plays a role in jasmonate-induced lateral root
      formation and lateral root positioning in Arabidopsis thaliana.
AB  - Jasmonic acid (JA) regulates a broad range of plant defense and developmental
      responses. COI1 has been recently found to act as JA receptor. In this report, we
      show that low micromolar concentrations of JA inhibited primary root (PR) growth
      and promoted lateral root (LR) formation in Arabidopsis wild-type (WT) seedlings.
      It was observed that the coi1-1 mutant was less sensitive to JA on pericycle cell
      activation to induce lateral root primordia (LRP) formation and presented
      alterations in lateral root positioning and lateral root emergence on bends. To
      investigate JA-auxin interactions important for remodeling of root system (RS)
      architecture, we tested the expression of auxin-inducible markers DR5:uidA and
      BA3:uidA in WT and coi1-1 seedlings in response to indole-3-acetic acid (IAA) and
      JA and analyzed the RS architecture of a suite of auxin-related mutants under JA
      treatments. We found that JA did not affect DR5:uidA and BA3:uidA expression in
      WT and coi1-1 seedlings. Our data also showed that PR growth inhibition in
      response to JA was likely independent of auxin signaling and that the induction
      of LRP required ARF7, ARF19, SLR, TIR1, AFB2, AFB3 and AXR1 loci. We conclude
      that JA regulation of postembryonic root development involves both auxin
      dependent and independent mechanisms.

PMID- 22658223
TI  - The spectrum of lymphoblastic, nodal and extranodal T-cell lymphomas:
      characteristic features and diagnostic dilemmas.
AB  - T-cell lymphomas represent a heterogeneous group of neoplasms that encompass
      considerable clinical, morphologic, and immunophenotypic variation. The diagnosis
      of T-cell lymphoma is challenging because of its relative rarity, the lack of an
      immunophenotypic marker of clonality, and significant morphologic overlap with
      infectious/inflammatory processes and neoplasms, including Hodgkin and other non
      Hodgkin lymphomas, and even mesenchymal or epithelial lesions. In the current
      World Health Organization classification of hematopoietic tumors, all except 1
      subtype (ie, T-lymphoblastic lymphoma) are recognized as mature neoplasms derived
      from postthymic T cells. In addition to T-lymphoblastic lymphoma, this review
      will focus on nodal and extranodal T-cell lymphomas and exclude T-cell lymphomas
      presenting primarily in the skin. Extranodal natural-killer-cell/T-cell lymphoma,
      nasal type, will also be discussed because the derivation of this lymphoma from
      natural killer and natural killer-like T cells shows morphologic and
      immunophenotypic features that overlap with other T-cell lymphomas. In this
      review, we discuss the salient clinicopathologic, immunophenotypic, and genetic
      features, as well as our approaches to the diagnosis of lymphoblastic, nodal, and
      extranodal T-cell lymphomas.

PMID- 22658224
TI  - Novel human polyomaviruses, Merkel cell polyomavirus and human polyomavirus 9, in
      Japanese chronic lymphocytic leukemia cases.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is the rarest adult leukemia in
      Japan, whereas it is the most common leukemia in the Western world. Recent
      studies from the United States and Germany suggest a possible etiological
      association between Merkel cell polyomavirus (MCPyV) and CLL, although no data
      have been reported from Eastern countries. To increase the volume of relevant
      data, this study investigated the prevalence and DNA loads of MCPyV and human
      polyomavirus 9 (HPyV9), another lymphotropic polyomavirus, in Japanese CLL cases.
      FINDINGS: We found that 9/27 CLL cases (33.3 %) were positive for MCPyV using
      quantitative real-time polymerase chain reaction analysis. The viral DNA loads
      ranged from 0.000017 to 0.0012 copies per cell. All cases were negative for
      HPyV9. One MCPyV-positive CLL case was evaluated by mutational analysis of the
      large T (LT) gene, which indicated the presence of wild-type MCPyV without a
      nucleotide deletion. DNA sequence analysis of the entire small T (ST) gene and
      the partial LT gene revealed that a Japanese MCPyV isolate, designated CLL-JK,
      had two nucleotide gaps when compared with the reference sequence of the North
      American isolate MCC350. CONCLUSIONS: This study provides the first evidence that
      MCPyV is present in a subset of Japanese CLL cases with low viral DNA loads.
      MCPyV and HPyV9 are unlikely to contribute directly to the development of CLL in
      the majority of Japanese cases. MCPyV isolated from the Japanese CLL cases may
      constitute an Asian group and its pathogenicity needs to be clarified in future
      studies.

PMID- 22658225
TI  - Endovascular treatment of inferior petrosal sinus dural arteriovenous fistula via
      percutaneous puncture of the superior ophthalmic vein.

PMID- 22658226
TI  - Reinforcement learning: computing the temporal difference of values via distinct
      corticostriatal pathways.
AB  - Midbrain dopamine neurons supposedly encode reward prediction error, but how
      error signals are computed remains elusive. Here, we propose a mechanism based on
      recent findings regarding corticostriatal circuits. Specifically, we propose that
      two distinct subpopulations of corticostriatal neurons differentially represent
      the animal's current and previous states/actions through unidirectional
      connectivity from one subpopulation to the other and strong recurrent excitation
      that exists only within the recipient subpopulation. These corticostriatal
      subpopulations selectively connect to the direct and indirect pathways of the
      basal ganglia, such that the temporal difference between the values of current
      and previous states/actions--the core of the error signal--can be computed. Our
      hypothesis suggests a unified view of basal ganglia functions and has important
      clinical implications.

PMID- 22658228
TI  - Hair toe tourniquet syndrome in a four-year-old boy.
AB  - BACKGROUND: Hair toe tourniquet syndrome is a condition in which a hair or thread
      encircles a digit and results in acute digital ischemia. It usually occurs in
      children under the age of 1 year. Prompt recognition and surgical removal of the
      constricting material can save the digit from irreversible tissue necrosis and
      the loss of digit. CASE REPORT: We report the first known case of hair toe
      tourniquet syndrome in a 4-year-old child, who had successful diagnosis and
      treatment of this condition. CONCLUSION: We suggest that hair toe tourniquet
      syndrome should be considered as a cause of acute digital swelling and
      discoloration in children of all ages.

PMID- 22658229
TI  - Long QT syndrome unmasked in an adult subject presenting with excited delirium.
AB  - BACKGROUND: Excited delirium is increasingly recognized as a risk factor for
      sudden death, though the specific pathophysiology of these deaths is typically
      unclear. OBJECTIVES: We describe a survivor of excited delirium that displayed a
      transient severe prolongation of the QT interval, suggesting unmasking of long QT
      syndrome as a possible mechanism of sudden death. CASE REPORT: A 30-year-old man
      was arrested by police for violent assaultive behavior. Officers at the scene
      noted confusion, nonsensical speech, sweating, and bizarre agitated behavior; he
      was transported to the Emergency Department for medical evaluation of possible
      excited delirium. His initial electrocardiogram revealed a markedly prolonged
      corrected QT interval of over 600 ms. Intravenous hydration and sodium
      bicarbonate were administered, with normalization of the QT; he was admitted and
      recovered uneventfully. CONCLUSIONS: We discuss the possible association between
      long QT syndrome and unexplained sudden deaths seen with excited delirium. Sodium
      bicarbonate may be considered when long QT syndrome is identified during or after
      agitated delirium, though its routine use cannot be recommended based on a case
      report.

PMID- 22658230
TI  - Local and global volume changes of subcortical brain structures from
      longitudinally varying neuroimaging data for dementia identification.
AB  - Quantification of structural changes in the human brain is important to elicit
      resemblances and differences between pathological and normal aging.
      Identification of dementia, associated with loss of cognitive ability beyond
      normal aging, and especially converters--the subgroup of individuals at risk for
      developing dementia--has recently gained importance. For this purpose atrophy
      markers have been explored and their effectiveness has been evaluated both cross
      sectionally and longitudinally. However, more research is needed to understand
      the dynamics of atrophy markers at different disease stages, which requires
      temporal analysis of local along with global changes. Unfortunately, most of the
      longitudinal neuroimaging data available in the clinical settings is acquired at
      largely varying time intervals. In the light of the above, this study presents a
      novel methodology to process longitudinal neuroimaging data acquired incompletely
      and at different time intervals, and explores complementary nature of local and
      global brain volume changes in identifying dementia. Results on the OASIS
      database demonstrate discriminative power of global atrophy in hippocampus (as
      early as two years after the first visit) for identifying demented cases, and
      local volume shrinkage of thalamus proper (as early as three years after the
      first visit) for differentiating converters.

PMID- 22658231
TI  - Is femoral nerve block necessary during total knee arthroplasty?: a randomized
      controlled trial.
AB  - There remains a lack of randomized controlled trials comparing methods of
      perioperative analgesia for total knee arthroplasty. To address this deficiency,
      a blinded, randomized controlled trial was conducted to compare the use of
      femoral nerve block (group F) and local anesthetic (group L). A sample of 55
      patients who met the inclusion criteria were randomized to either group. No
      significant differences in the most severe pain score or 36-Item Short Form
      Health Survey, The Western Ontario and McMaster Universities Arthritis Index
      (WOMAC), or Oxford scores were observed between groups. However, the Knee Society
      score was significantly higher in group F. In addition, group F used
      significantly fewer micrograms of intravenous fentanyl in the first 24 hours.
      Balancing the risks of femoral nerve block with those of increased systemic
      narcotic delivery should be performed on a case-by-case basis.

PMID- 22658232
TI  - Unicompartmental knee arthroplasty relieves pain and improves function more than
      total knee arthroplasty.
AB  - This study compared outcomes as assessed by 12-item Short-Form Health Survey (SF
      12) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
      between patients who underwent unicompartmental (UKA) and patients who underwent
      total knee (TKA) arthroplasty. We prospectively collected preoperative
      demographic and SF-12 and WOMAC data on 128 TKAs and 70 UKAs. Postoperatively, SF
      12 and WOMAC outcomes were recorded during annual follow-up visits. At baseline,
      patients who underwent UKA had a higher Charlson Comorbidity Index than patients
      who underwent TKA; otherwise, preoperative characteristics were similar. At a
      mean follow-up of 3.0 years for UKA and 2.9 years for TKA, patients who underwent
      UKA reported higher SF-12 physical component and mental component scores and
      WOMAC pain/stiffness/physical function scores (confirmed with multivariate
      analysis). Furthermore, patients who underwent UKA had significantly larger
      improvements in both SF-12 outcomes and WOMAC pain and physical function scores
      from baseline than did patients who underwent TKA.

PMID- 22658233
TI  - Observation of photocatalytic dissociation of water on terminal Ti sites of
      TiO2(110)-1 * 1 surface.
AB  - The water splitting reaction based on the promising TiO(2) photocatalyst is one
      of the fundamental processes that bears significant implication in hydrogen
      energy technology and has been extensively studied. However, a long-standing
      puzzling question in understanding the reaction sequence of the water splitting
      is whether the initial reaction step is a photocatalytic process and how it
      happens. Here, using the low temperature scanning tunneling microscopy (STM)
      performed at 80 K, we observed the dissociation of individually adsorbed water
      molecules at the 5-fold coordinated Ti (Ti(5c)) sites of the reduced TiO(2) (110)
      1 * 1 surface under the irradiation of UV lights with the wavelength shorter than
      400 nm, or to say its energy larger than the band gap of 3.1 eV for the rutile
      TiO(2). This finding thus clearly suggests the involvement of a photocatalytic
      dissociation process that produces two kinds of hydroxyl species. One is always
      present at the adjacent bridging oxygen sites, that is, OH(br), and the other
      either occurs as OH(t) at Ti(5c) sites away from the original ones or even
      desorbs from the surface. In comparison, the tip-induced dissociation of the
      water can only produce OH(t) or oxygen adatoms exactly at the original Ti(5c)
      sites, without the trace of OH(br). Such a difference clearly indicates that the
      photocatalytic dissociation of the water undergoes a process that differs
      significantly from the attachment of electrons injected by the tip. Our results
      imply that the initial step of the water dissociation under the UV light
      irradiation may not be reduced by the electrons, but most likely oxidized by the
      holes generated by the photons.

PMID- 22658234
TI  - Psychiatric disorders in patients with essential tremor.
AB  - BACKGROUND: Previous studies have reported that a consistent proportion of
      patients with Essential Tremor may have psychiatric disorders but it is unclear
      whether these disorders are increased in frequency as compared to healthy
      subjects. METHODS: In a case-control study, we adopted the structured interviews
      for DSM-IV, SCID-I and SCID-II, to investigate psychiatric and personality
      disorders in 37 ET patients and 34 healthy subjects. As cognitive changes in ET
      may be a confounding factor we enrolled patients and healthy control subjects
      without cognitive dysfunction. RESULTS: SCID-I showed that Axis-I psychiatric
      disorders, mainly depressive disorders, were more frequent in ET patients (20 of
      37; 54%) than in healthy subjects (8 of 34; 22%) (p < 0.01). Depressive disorders
      were more frequent in patients with a family history of ET (p < 0.05) in
      comparison to patients without a family history. SCID-II disclosed that the
      frequency of personality disorders was similar in patients with ET and healthy
      subjects. CONCLUSION: Psychiatric disorders may be associated to the neurological
      manifestations of ET.

PMID- 22658235
TI  - Development of quality of care interventions for adult patients on home
      parenteral nutrition (HPN) with a benign underlying disease using a two-round
      Delphi approach.
AB  - BACKGROUND & AIMS: HPN patients with benign diseases deserve professional care as
      they have to deal with complex techniques and risk potentially dangerous
      complications. The aim was to highlight main outcome quality indicators and to
      develop a set of key interventions to direct multidisciplinary teams in providing
      qualitative care. METHODS: A two-round Delphi approach was used to build
      consensus on the most important outcome indicators and on 59 interventions
      identified in existing guidelines on HPN. Comments and interventions newly
      identified in the first round were co-evaluated in the second round. RESULTS: 29
      experts from 9 countries completed the two-round Delphi approach. The outcome
      indicators rated as the most important are 1) incidence of catheter-related
      infections, 2) incidence of readmission and quality of life (shared second place)
      and 3) incidence of dehydration. Sixty eight of a total of 89 interventions were
      considered as important for the quality of care, of which 46 are based on
      published guidelines and 22 were newly suggested by the Delphi panel.
      CONCLUSIONS: Using a two-round Delphi approach, consensus was reached for the
      majority of interventions concerning HPN patients with benign diseases. This set
      of 68 interventions could be of use as a starting point for quality-improvement
      programs.

PMID- 22658236
TI  - Topical application of 5-aminolevulinic acid followed by 595-nm pulsed dye laser
      irradiation for the treatment of recalcitrant port-wine stains: a primary study.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of topical application of 5
      aminolevulinic acid (ALA) followed by pulsed dye laser (PDL) irradiation for the
      treatment of recalcitrant port-wine stain (PWS). METHODS: Thirty-five patients
      (19 females and 16 males) with recalcitrant PWS were treated with topical
      application of 20% ALA and then irradiated with a 595-nm PDL (energy density of
      6.5-9.0 J/cm(2) and pulse duration of 6 or 10 ms) at 6-8 weeks intervals.
      Clinical improvement of lesions was evaluated by comparing photographs of lesions
      at baseline and 2 months after the last treatment. RESULTS: Topical ALA spreading
      followed by irradiation with a 595-nm PDL improved PWS in 21 out of 35 patients
      who were previously recalcitrant to PDL treatment alone. Side effects were
      limited to transient erythema, vesicle formation, edema and mild purpura with no
      obvious subsequent scarring or undesirable pigment changes. CONCLUSION: The
      topical application of ALA followed by irradiation with a 595-nm PDL is an
      effective and safe treatment for PWS recalcitrant to PDL therapy alone.

PMID- 22658237
TI  - Clinical negligence, litigation and healthcare-associated infections.
AB  - BACKGROUND: Litigation costs resulting from clinical negligence claims involving
      healthcare-associated infections are a significant but underappreciated cost to
      healthcare organizations. In England these claims are handled on behalf of the
      National Health Service (NHS) organizations by the NHS Litigation Authority
      (NHSLA). The total number of claims and the amounts awarded have increased
      significantly in recent years. AIM: To determine whether the recent significant
      reductions in meticillin-resistant Staphylococcus aureus (MRSA) bloodstream
      infection (BSI) and Clostridium difficile infections in England have had an
      effect on the number and value of NHSLA claims relating to these infections.
      METHODS: Data obtained from the NHSLA relating to claims mentioning C. difficile
      or MRSA from 2003 to 2010 were correlated with mandatory surveillance data from
      the Health Protection Agency for these infections. FINDINGS: The rate of NHSLA
      claims for MRSA has decreased in line with reductions in BSI for this infection
      (0.007 per BSI between 2003/4-2006/7 to 0.0017 per BSI between 2007/8 and
      2010/11), but there was no significant change in claims relating to C. difficile
      infection. Overall the amounts awarded for successful claims have decreased
      significantly from a total of L76,846 for the period 1997/8-2006/7 to L24,821 for
      the period 2007/8-2010/11. CONCLUSIONS: The number of litigation claims involving
      MRSA has recently decreased significantly in line with surveillance data. There
      was no observed effect on claims involving C. difficile. The amounts awarded for
      successful claims for both infections have also fallen, although the reasons for
      this are not clear.

PMID- 22658238
TI  - Nosocomial H1N1 infection during 2010-2011 pandemic: a retrospective cohort study
      from a tertiary referral hospital.
AB  - This study aimed to estimate the incidence of hospital transmission of influenza
      A subtype H1N1 [A(H1N1)], to identify high-risk areas for such transmission and
      to evaluate common characteristics of affected patients. In this single-centre
      retrospective cohort study, 10 patients met the criteria for hospital-acquired
      A(H1N1) infection over a three-month period. All affected patients required an
      escalation of their care and the mortality rate was 20%. Clinicians should be
      aware of the risk of nosocomial A(H1N1) infection that exists despite routine
      infection control measures and should consider additional control measures
      including vaccination of hospital inpatients and healthcare staff.

PMID- 22658239
TI  - Differences between a single session and repeated sessions of 1 Hz TMS by double
      cone coil prefrontal stimulation for the improvement of tinnitus.
AB  - Tinnitus related distress is associated with increased activity in the anterior
      cingulate cortex (ACC). In a recent study, it was demonstrated that a single
      session of low frequency prefrontal TMS using a double-cone coil (DCC) modulating
      the ACC (AC/DC TMS, anterior cingulate cortex targeted modulation by Double-Cone
      coil) yields a transient improvement in subjects with chronic tinnitus. An
      increasing number of studies demonstrated that repeated sessions of low frequency
      TMS to the temporoparietal area can significantly improve tinnitus complaints.
      Our aim is to determine the extent to which repeated sessions of AC/DC TMS can
      modulate tinnitus in comparison to a single session. Seventy-three tinnitus
      patients received a single (N = 46) or repetitive (N = 27) session(s) of TMS
      using a DCC placed over the prefrontal cortex. Our results indicate that both
      single sessions as well as multiple sessions (i.e. 8 sessions) of AC/DC TMS
      suppress both tinnitus distress (respectively 7.60% vs. 26.19%) and tinnitus
      intensity (respectively 7.12% vs. 19.60%) transiently. It was further shown that
      multiple sessions of AC/DC TMS generate a higher suppression effect in comparison
      to a single session of AC/DC TMS and that more patients responded to repeated
      sessions of 1 Hz stimulation in comparison to a single session. Our findings give
      further support to the fact that non-auditory areas are involved in tinnitus
      intensity and tinnitus distress and that more patients respond to repeated
      sessions with a higher suppression effect in comparison to patients who received
      a single session, suggesting that the approach of daily TMS sessions is relevant.

PMID- 22658240
TI  - Churg-Strauss, a rare cause of intracerebral haemorrhage.
AB  - Intracerebral haemorrhage (ICH) is a common and devastating condition. We
      describe a 43-year-old man with the rare Churg-Strauss syndrome, which was
      diagnosed after he presented with an ICH. He was managed initially
      neurosurgically with clot evacuation and craniectomy. Post-investigation and
      diagnosis of Churg-Strauss, treatment was with high dose methylprednisolone (then
      oral prednsiolone) and intravenous cyclophosphamide. Clinicians should be aware
      that Churg-Strauss syndrome can, rarely, be a cause of ICH. Given its high
      morbidity and mortality, it is important that patients are diagnosed promptly and
      managed appropriately.

PMID- 22658241
TI  - Progressive multifocal leukoencephalopathy (PML) mimicking high-grade glioma on
      delayed F-18 FDG PET imaging.
AB  - The purpose of our study was to determine the increase in F-18 fluorodeoxyglucose
      (FDG) uptake in a patient with progressive multifocal leukoencephalopathy (PML)
      between early and late scan times using positron emission tomography (PET)
      imaging with F-18 FDG at conventional (60 minutes [min] after injection, PET(60))
      and delayed (300 min after injection, PET(300)) intervals. PET(60) and PET(300)
      imaging was performed on a pathologically proven PML lesion. The PML lesion in
      the posterior fossa exhibited an increase in F-18 FDG uptake of 52% between early
      and late times, which was in the range of that in high-grade gliomas. Thus, dual
      time-point PET with F-18 FDG may not be able to differentiate between infectious
      and malignant brain lesions.

PMID- 22658242
TI  - A 71-year-old woman with an intracranial dural-based mesenchymal chondrosarcoma.
AB  - Intracranial mesenchymal chondrosarcoma is a rare, high-grade malignancy with the
      highest prevalence in young adults. Because of its rarity, most data regarding
      survival are limited to case studies and small series. We present a 71-year-old
      woman with an intracranial dural based mesenchymal chondrosarcoma located in the
      anterior skull base, to our knowledge the oldest patient reported with this
      tumor.

PMID- 22658243
TI  - Structural and anticancer properties of hydrogen bonded diphenyl phosphate
      adducts of Pt(IV) complexes: the importance of pKa matching.
AB  - Co-crystallisation of diphenyl phosphate (Hdpp) with anticancer active Pt(IV)
      complexes of the type cis,trans,cis-[PtCl(2)(OH)(2)(am(m)ine)(2)] has produced a
      new type of supramolecular adduct with short hydrogen bonds from the Hdpp
      molecules to the hydroxide ligands in all cases. X-ray crystallographic analysis
      showed within the adduct cis,trans-[PtCl(2)(en)(OH(2))(2)](dpp)(2) (1) a hydrogen
      bond length of 2.341(6) A; the shortest O ... O distance reported in the
      literature. Similar, though longer hydrogen bonds were observed in three other
      complexes: [PtCl(2)(OH)(NH(3))(2)(OH(2))]dpp.3H(2)O (2), trans
      [Pt(mal)(OH)(OH(2))(S,S-chxn)]dpp.3H(2)O (3), and trans-[Pt(ox)(OH)(OH(2))(S,S
      chxn)]dpp.2H(2)O (4). Co-crystallisation with Hdpp leads to higher aqueous
      solubility than the parent complexes indicating the potential of the adducts for
      use as active pharmaceutical ingredients. Anticancer testing of
      [Pt(mal)(OH)(OH(2))(S,S-chxn)]dpp.3H(2)O (3) showed in vitro cytotoxicity is low,
      as expected for Pt(IV) prodrugs, yet substantial tumour growth inhibition was
      observed in an in vivo ADJ/PC6 tumour model, with activity retained at maximum
      tolerated dose (MTD)/2 and MTD/4.

PMID- 22658244
TI  - Impact of gender on three-month outcome and left ventricular remodeling after
      transfemoral transcatheter aortic valve implantation.
AB  - Transarterial aortic valve implantation (TAVI) is a promising method for the
      treatment of high-risk patients with aortic stenosis. Because gender differences
      are known in aortic stenosis, the aim of this study was to compare procedural and
      short-term outcomes, left ventricular remodeling, and inflammatory status after
      TAVI in men and women. One hundred consecutive patients (42 men, 58 women) who
      underwent transfemoral TAVI (CoreValve in 83%, SAPIEN in 17%) were prospectively
      analyzed. Aortic stenosis severity was higher in women (mean valve area 0.7 +/-
      0.3 vs 0.8 +/- 0.2 cm(2)). Women had better ejection fractions, smaller end
      diastolic and end-systolic diameters, and more concentric hypertrophy at
      baseline. There were no differences in device success rate (99%), 30-day total
      mortality (2.4% in men, 3.4% in women), stroke (2.4% in men, 1.7% in women), or
      pacemaker rate (26.2% in men, 15.5% in women). Periprocedural complications and 3
      month outcome were not different between the genders. After TAVI, regression of
      hypertrophy occurred in men and women, but improvement of the ejection fraction
      was significant only in women. N-terminal pro-B-type natriuretic peptide
      decreased to similar levels in the 2 genders. C-reactive protein and interleukin
      6, elevated at baseline more in men than in women, decreased after TAVI and
      normalized at 3 months only in women. In conclusion, women clinically benefit
      from TAVI to a degree similar to that of men. However, there are gender
      differences involving the recovery response of the left ventricle after TAVI.

PMID- 22658245
TI  - Secondary causes of dyslipidemia.
AB  - The causes of the lipid disorders in patients referred to specialty clinics for
      difficult-to-treat dyslipidemias are likely multifactorial. However, the
      importance of evaluating for secondary causes is unclear. The investigators
      performed a chart review of new patients referred to the University of Michigan
      Lipid Clinic from January 2004 to June 2011 (n = 824) to evaluate for the
      prevalence of several secondary causes of dyslipidemia. In addition to
      lipoproteins, new patients were assessed for secondary dyslipidemias by a
      standardized protocol consisting of laboratory testing, a nutritional evaluation,
      and medical history. These data were evaluated to determine the prevalence of
      several secondary causes of dyslipidemia. A total of 363 separate factors were
      identified in the 824 patients that were thought to be potential secondary causes
      of dyslipidemia. Because some patients (n = 83 [10%]) had multiple conditions,
      there were 230 (28% of the cohort) with >=1 potential secondary dyslipidemias.
      The most common conditions were excessive alcohol intake (n = 82 [10%]),
      uncontrolled diabetes mellitus (n = 68 [8%]), and overt albuminuria. Although
      other causes occurred less frequently (each individually found in <5% of
      patients), altogether they were present in a substantial portion of patients (n =
      102 [12%]). In conclusion, nearly 1/3 of patients referred to a specialty clinic
      had identifiable secondary conditions plausibly contributing to their
      dyslipidemia. Numerous disorders were identified, with diabetes mellitus and
      excessive alcohol being the most common.

PMID- 22658246
TI  - Serum 25-hydroxyvitamin D concentration and mortality from heart failure and
      cardiovascular disease, and premature mortality from all-cause in United States
      adults.
AB  - We aimed to examine associations between serum 25-hydroxyvitamin D (25[OH]D)
      concentration and mortality from heart failure (HF) and cardiovascular disease
      (CVD) and premature death from all causes using data from the Third National
      Health and Nutrition Examination Survey, which included 13,131 participants
      (6,130 men, 7,001 women) >=35 years old at baseline (1988 to 1994) and followed
      through December 2000. Premature death was defined all-cause death at <75 years
      of age. Results indicated that during an average 8-year follow-up, there were
      3,266 deaths (24.9%) including 101 deaths from HF, 1,451 from CVD, and 1,066
      premature all-cause deaths. Among HF deaths, 37% of decedents had serum 25(OH)D
      levels <20 ng/ml, whereas only 26% of those with non-HF deaths had such levels (p
      <0.001). Multivariate-adjusted Cox model indicated that subjects with serum
      25(OH)D levels <20 ng/ml had 2.06 times higher risk (95% confidence interval 1.01
      to 4.25) of HF death than those with serum 25(OH)D levels >=30 ng/ml (p <0.001).
      In addition, hazard ratios (95% confidence intervals) for premature death from
      all causes were 1.40 (1.17 to 1.68) in subjects with serum 25(OH)D levels <20
      ng/ml and 1.11 (0.93 to 1.33) in those with serum 25(OH)D levels of 20 to 29
      ng/ml compared to those with serum 25(OH)D levels >=30 ng/ml (p <0.001, test for
      trend). In conclusion, adults with inadequate serum 25(OH)D levels have
      significantly higher risk of death from HF and all CVDs and all-cause premature
      death.

PMID- 22658247
TI  - Use of social support during communication about sickle cell carrier status.
AB  - OBJECTIVE: To examine the use of social support behaviors by primary care
      providers during delivery of positive newborn screening results for Sickle Cell
      Anemia carrier status. METHODS: Transcripts from 125 primary care providers who
      conveyed Sickle Cell Anemia carrier status to standardized parents were content
      analyzed using categories derived from Cutrona and Suhr's social support
      taxonomy. Frequencies and cross-tabulation matrices were calculated to study
      providers' social support utilization. RESULTS: Results showed most primary care
      providers (80%) incorporate social support behaviors into delivery of Sickle Cell
      Anemia carrier results and most frequently employed social network (61.6%) and
      informational support (38.4%) behaviors. Providers used tangible aid (8%), esteem
      (1.6%), and emotional support (9.6%) behaviors less frequently. CONCLUSION:
      Cutrona and Suhr's taxonomy may be a useful tool for assessing supportive
      communication during the delivery of Sickle Cell Anemia carrier status and could
      be incorporated into population scale assessments of communication quality
      assurance. PRACTICE IMPLICATIONS: Primary care providers may need training in how
      to adapt supportive behaviors to parents' needs during communication of Sickle
      Cell Anemia carrier status. They also may benefit from specific training about
      how to use esteem and emotional support.

PMID- 22658248
TI  - Endometrial cancer survivors are unsatisfied with received information about
      diagnosis, treatment and follow-up: a study from the population-based PROFILES
      registry.
AB  - OBJECTIVE: To evaluate perceived level of and satisfaction with information
      received by endometrial cancer survivors, and to identify associations with socio
      demographic and clinical characteristics. METHODS: All patients diagnosed with
      endometrial cancer between 1998 and 2007, registered in the Eindhoven Cancer
      Registry, received a questionnaire including EORTC-QLQ-INFO25. RESULTS: Seventy
      seven percent responded (n=742). Most patients indicated receiving quite a bit
      information about their disease and medical tests. However, most patients were
      not (54%) or a little (24%) informed about the cause of their disease, and
      possible side effects (36%; 27%). Especially information about additional help,
      rehabilitation, psychological assistance, and expected results on social and
      sexual life was lacking. Five percent was not or a little (36%) satisfied. Four
      percent found the information not or a little (35%) helpful. Fifteen percent
      preferred more information. Younger age, more recent diagnosis, radiotherapy,
      absence of comorbidities, having a partner, having received written information,
      and higher educational level were associated with higher perceived information
      receipt. CONCLUSION: Many endometrial cancer survivors are unsatisfied with
      received information. Several areas of information provision are experienced as
      insufficient. PRACTICE IMPLICATIONS: More patient-tailored information is
      probably needed to provide optimal information. Implementation of Survivorship
      Care Plans might be a way to achieve this.

PMID- 22658249
TI  - Evaluation of peri-operative epidural analgesia with ropivacaine, ropivacaine and
      sufentanil, and ropivacaine, sufentanil and epinephrine in isoflurane
      anesthetized dogs undergoing tibial plateau levelling osteotomy.
AB  - The purpose of this study was to compare four epidural protocols for peri
      operative analgesia in dogs undergoing tibial plateau levelling osteotomy. Forty
      client-owned dogs were randomly assigned to one of four treatments - groups R0.5
      and R1 received 0.5mg/kg and 1mg/kg ropivacaine, respectively. Group SR0.5
      received 1 MUg/kg sufentanil plus 0.5mg/kg ropivacaine, and group SER0.5 received
      1 MUg/kg sufentanil, 0.5mg/kg ropivacaine plus 6 MUg/kg epinephrine. Dilution,
      when required, was performed with saline, so that the injected volume was always
      0.2 mL/kg. Intra-operatively, nociception assessment was based on the evaluation
      of changes in heart rate, respiratory rate and mean arterial pressure. Post
      operative pain assessment was performed using the Glasgow visual analogue pain
      scale, and an ad hoc multifactorial pain score. Motor block was evaluated using a
      modified Bromage score. Intra-operatively, none of the animals was hypotensive.
      All groups except SER0.5 required rescue intra-operative fentanyl (40%, 30% and
      40% of the animals in groups R0.5, R1 and SR0.5, respectively). Group SER0.5
      showed lower post-operative pain scores, and group R1 significantly greater motor
      block, compared to the other treatment groups. None of the dogs had urinary
      retention. Epidural sufentanil-epinephrine-ropivacaine provided superior peri
      operative analgesia compared to the other treatments, without producing
      clinically relevant side effects.

PMID- 22658250
TI  - Empirical review supporting the application of the "pain assessment as a social
      transaction" model in pediatrics.
AB  - Despite decades of research, national mandates, and widespread implementation of
      guidelines, recent reports suggest that the quality of pain assessment and
      management in hospitalized children remains suboptimal. The mismatch between what
      is advocated and what is done in practice has led experts to argue for a
      conceptual shift in thinking, where the pain assessment process is viewed from a
      complex social communication or transaction framework. This article examines the
      empirical evidence from the recent pediatric pain assessment and decision-making
      literature that supports adaptation of Schiavenato and Craig's "Pain Assessment
      as a Social Transaction" model in explaining pediatric acute pain management
      decisions. Multiple factors contributing to children's pain experiences and
      expressions are explored, and some of the difficulties interpreting their pain
      scores are exposed. Gaps in knowledge related to nurses' clinical pain management
      decisions are identified, and the importance of children's and parents'
      preferences and roles and the influence of risks and adverse events on decision
      making are identified. This review highlights the complexity of pediatric nurses'
      pain management decisions toward the clinical goal of improving comfort while
      minimizing risk. Further study evaluating the propositions related to nurses'
      decisions to intervene is needed in pediatric clinical settings to better
      synthesize this model for children.

PMID- 22658251
TI  - Older adults' experiences of transitions between care settings at the end of life
      in England: a qualitative interview study.
AB  - CONTEXT: Providing care that is shaped around the needs of patients, carers, and
      families is a challenge in the last months of life, as moves between home and
      institutions may be frequent. Despite this, there have been few studies of end-of
      life transitions in the U.K. OBJECTIVES: To explore older adults' experiences as
      they move between places of care at the end of life. METHODS: In-depth
      qualitative interviews and thematic analysis of the data were performed. Thirty
      adults aged between 69 and 93 years took part. All were judged by their
      physicians to be in the last year of life, diagnosed with heart failure (13),
      lung cancer (14), and stroke (3). Sixteen participants were from the lowest
      socioeconomic groups. RESULTS: Four themes were identified from the data relating
      to 1) the prioritization of institutional processes, 2) support across settings,
      3) being heard, and 4) dignity. As they moved between different settings, much of
      the care received by older adults was characterized by inflexibility and a
      failure of professional carers to listen. Liaison between and within services was
      not always effective, and community support after a hospital admission was
      perceived to be, on occasions, absent, inappropriate, or excessive. CONCLUSION:
      Qualitative study of transitions provides valuable insights into end-of-life
      care, even in countries where there are few financial barriers to services. This
      study has highlighted a need for continued attention to basic aspects of care and
      communication between professionals and with patients.

PMID- 22658252
TI  - Symptom clusters in patients with advanced cancer: a reanalysis comparing
      different statistical methods.
AB  - CONTEXT: The clinical relevance of symptom cluster research remains questionable
      if inconsistencies, partially attributable to the varying statistical analyses
      used, exist. OBJECTIVES: To investigate whether symptom clusters identified were
      consistent using three different statistical methods and to observe the temporal
      pattern of clusters. A secondary objective was to compare symptom clustering in
      responders and nonresponders to radiotherapy over time. METHODS: Reanalysis of an
      existing data set compiled from 1296 patients with advanced cancer was performed
      using hierarchical cluster analysis (HCA) and exploratory factor analysis (EFA)
      to extract symptom clusters at baseline, 1-, 2-, 4-, 8-, and 12-week follow-up
      time points. Findings were compared with results obtained using principal
      component analysis (PCA) in our previously published study. The original sample
      was further divided into two subgroups: responders and nonresponders. The symptom
      clusters present in each subgroup were examined using PCA, HCA, and EFA at the
      same time points as mentioned above. RESULTS: The symptom cluster findings of HCA
      and PCA correlated more frequently with each other than either did with the
      results of EFA. Complete consensus in all three statistical methods was never
      reached at any assessment time point in the present study. Increasingly diverging
      patterns of symptom cluster development over time were observed in the responder
      vs. nonresponder subgroups. Symptom pairs comprising anxiety and depression or
      fatigue and drowsiness consistently presented in the same cluster despite the
      shifting of other symptoms in the cluster over time. CONCLUSION: The presence and
      composition of symptom clusters identified varied depending on which statistical
      analysis method was used. A key step in achieving consistency in symptom cluster
      research involves the utilization of a common analytical method.

PMID- 22658253
TI  - Inhibition of lysosomal function in macrophages incubated with elevated glucose
      concentrations: a potential contributory factor in diabetes-associated
      atherosclerosis.
AB  - OBJECTIVE: People with diabetes have an elevated risk of atherosclerosis. The
      accumulation of lipid within macrophage cells in the artery wall is believed to
      arise via the uptake and subsequent processing of modified low-density
      lipoproteins (LDL) via the endo-lysosomal system. In this study the effects of
      prolonged exposure to elevated glucose upon macrophage lysosomal function was
      examined to determine whether this contributes to modulated protein catabolism.
      METHODS: Human monocytes were isolated from white-cell concentrates and
      differentiated, in vitro, into monocyte-derived macrophages over 11 days in
      medium containing 5-30 mmol/L glucose. Murine macrophage-like J774A.1 cells were
      incubated similarly. Lysosomal cathepsin (B, D, L and S) and acid lipase
      activities were assessed using fluorogenic substrates; cathepsin protein levels
      were examined by Western blotting. Lysosomal numbers were examined using the
      lysomotropic fluorescent dye LysoTracker DND-99, measurement of aryl sulfatase
      activity, and quantification of lysosome-associated membrane glycoprotein-1 (LAMP
      1) by Western blotting. RESULTS: Exposure to elevated glucose, but not mannitol,
      resulted in a concentration-dependent decrease in the activity, and to a lesser
      extent protein levels, of four lysosomal cathepsins. Acid lipase activity was
      also significantly reduced. Arysulfatase activity, LAMP-1 levels and lysosomal
      numbers were also decreased at the highest glucose concentrations, though to a
      lesser extent. CONCLUSION: Long term exposure of human and murine macrophage
      cells to elevated glucose levels result in a depression of lysosomal proteolytic
      and lipase activities. This may result in decreased clearance and cellular
      accumulation of (lipo)proteins and contribute to the accumulation of modified
      proteins and lipids in diabetes-associated atherosclerosis.

PMID- 22658254
TI  - Early abciximab administration before primary percutaneous coronary intervention
      improves clinical outcome in diabetic patients with ST-segment elevation
      myocardial infarction (EUROTRANSFER Registry).
AB  - BACKGROUND: Diabetes is an important determinant of prognosis in patients with ST
      segment elevation myocardial infarction (STEMI). Limited data are available
      concerning benefits and risks of upstream abciximab administration in diabetic
      patients. Thus, the objective of the study was to assess the impact of early
      abciximab administration before primary angioplasty (PCI) for STEMI in diabetic
      patients. METHODS: Data were gathered for 1650 consecutive STEMI patients
      transferred for primary PCI from hospital networks in seven countries in Europe
      from November 2005 to January 2007 (the EUROTRANSFER Registry population).
      Patients were stratified by diabetes mellitus presence and then by abciximab
      administration strategy (early - more than 30 min before PCI vs. late). RESULTS:
      Diabetes mellitus was diagnosed in 262 (15.9%) patients. Patients with diabetes
      mellitus were high-risk individuals, with advanced age, higher prevalence of
      comorbidities and increased risk of ischemic events during follow-up in
      comparison to non-diabetic patients. A total of 1086 patients who received
      abciximab were identified. Strategy of early abciximab administration was
      associated with enhanced infarct-related artery patency before PCI, and improved
      epicardial flow after PCI in both diabetic and non-diabetic patients.
      Importantly, early abciximab in diabetic patients led to the decrease in ischemic
      events, including 30-day (OR 0.260, 95% CI 0.089-0.759, p = 0.012) and 1-year (OR
      0.273, 95% CI 0.099-0.749, p = 0.012) mortality reduction. However, only a trend
      toward improved survival was confirmed after adjustment for potential
      confounders. On the contrary, the reduction of 30-day (OR 0.620, 95% CI 0.334
      1.189, p = 0.16) and 1-year (OR 0.643, 95% CI 0.379-1.089, p = 0.10) mortality
      rates was not significant among non-diabetic patients. CONCLUSIONS: Early
      administration of abciximab improves infarct-related artery patency before and
      after primary PCI, and leads to improved survival in diabetic STEMI patients.

PMID- 22658255
TI  - Deterioration of glucose homeostasis in type 2 diabetic patients one year after
      beginning of statins therapy.
AB  - OBJECTIVE: We evaluated the long-term effects of rosuvastatin and simvastatin on
      insulin sensitivity and secretion in patients with well-controlled type 2
      diabetes. METHODS: After a 3 weeks run-in, 27 eligible patients were randomly
      assigned to receive either rosuvastatin 20 mg daily (Group 1) or simvastatin 20
      mg daily (Group 2) for 6 months; thereafter they were switched to the other
      treatment for additional 6 months. Patients were recruited among individuals
      attending the outpatient service of the Diabetology Unit of the "Policlinico Tor
      Vergata" University Hospital, Rome, Italy. Serum lipids, glucose and insulin,
      glycated hemoglobin, C-reactive protein, TNF-alpha, leptin, adiponectin, insulin
      sensitivity by euglycemic-hyperinsulinemic clamp, beta-cells function by HOMA
      beta were assessed at months 0, 6 and 12. Additionally, endothelial function was
      assessed by use of the brachial artery reactivity technique. RESULTS: Besides
      marked reduction in lipid levels, glycated hemoglobin significantly increased
      from baseline after 12 months in both Group 1 (+0.8 +/- 0.2%, p < 0.001) and
      Group 2 (+0.9 +/- 0.3%; p < 0.001). Similar trends were observed for fasting
      glucose in both groups. No changes in insulin sensitivity were detected
      throughout the study, whereas HOMA-beta significantly decreased from baseline
      after 12 months in both Group 1 (-21.9%, p < 0.01) and Group 2 (-38.9%; p <
      0.001). In addition, both treatments similarly decreased C-reactive protein and
      leptin, as well as improved endothelial function. No changes in anthropometric
      measures were observed. CONCLUSIONS: In well-controlled type 2 diabetic patients
      both rosuvastatin and simvastatin significantly impaired glycemic control and
      insulin secretion, without affecting insulin sensitivity.

PMID- 22658256
TI  - META060 attenuates TNF-alpha-activated inflammation, endothelial-monocyte
      interactions, and matrix metalloproteinase-9 expression, and inhibits NF-kappaB
      and AP-1 in THP-1 monocytes.
AB  - BACKGROUND: Cytokine-induced monocyte-endothelial interaction and vascular
      inflammation play a critical role in atherogenesis. A modified hop extract,
      META060, was identified as an inhibitor of inflammatory mediators in human
      rheumatoid arthritis synovial fibroblasts. OBJECTIVE: To determine how META060
      may impact the initial stages of atherosclerosis, we investigated the effects of
      META060 in endothelial and monocyte cell models. METHODS: and results: TNF-alpha
      (10 ng/mL)-activated human monocytic THP-1 cells adhered to human aortic
      endothelial cells (HAECs); pre-treatment of cells with META060 (10 MUg/mL)
      significantly inhibited cell adhesion. META060 (1-20 MUg/mL) inhibited TNF-alpha
      induced expression of inflammatory mediators including IL-1beta, MCP-1 and RANTES
      in HAECs and THP-1 cells. TNF-alpha- or LPS-mediated MMP-9 protein levels
      (measured by an immunoassay) and enzyme activity (determined by zymography) were
      inhibited by META060 in a dose-dependent manner. Data from transcription factor
      screening assays showed that META060 selectively inhibited NF-kappaB and AP-1 in
      THP-1 cells, suggesting that META060 regulated inflammatory markers through gene
      regulation. CONCLUSION: META060 inhibited monocyte-endothelial cell interactions
      and suppressed multiple biomarkers of inflammation in both a monocytic cell line
      and an endothelial cell line. MMP-9 expression and activity also were inhibited.
      These effects resulted in part from META060's inhibition of transcription factors
      NF-kappaB and AP-1. META060 may have beneficial effects for prevention or
      treatment of cardiovascular diseases by ameliorating inflammation and plaque
      destabilization, which are hallmarks of atherosclerosis.

PMID- 22658257
TI  - Salvianolic acid B inhibits macrophage uptake of modified low density lipoprotein
      (mLDL) in a scavenger receptor CD36-dependent manner.
AB  - CD36, a class B scavenger receptor, has been implicated in the pathogenesis of a
      host of vascular inflammatory diseases. Through a high-throughput screening (HTS)
      assay for CD36 antagonist, we previously identified salvianolic acid B (SAB), a
      hydrophilic component derived from the herb Danshen, as a potential candidate.
      Danshen, the dried roots of Salvia miltiorrhiza, has been widely used in China
      for the prevention and treatment of atherosclerosis-related disorders. Previous
      studies showed that SAB acted as an anti-oxidant by preventing lipid peroxidation
      and oxidized LDL (oxLDL) formation. The present study was to investigate the
      specificity and efficacy of SAB in the inhibition of CD36-mediated lipid uptake.
      SAB reduced modified LDL (mLDL) uptake in a dose-dependent manner in phorbol-12
      myristate-13-acetate (PMA)-stimulated THP-1 and RAW 264.7 cells. In the CD36
      silenced THP-1 cells, SAB had no effect in reducing mLDL uptake, whereas its
      overexpression in CHO cells reinstates the effect, indicating a specific
      involvement of SAB in antagonizing the CD36's function. Surface plasmon resonance
      (SPR) analysis revealed a direct binding of SAB to CD36 with a high affinity
      (K(D) = 3.74 MUM), confirming physical interactions of SAB with the receptor.
      Additionally, SAB reduced oxLDL-induced CD36 gene expression in the cultured cell
      lines and primary macrophages. In ApoE KO mice fed a high fat diet, SAB reduced
      CD36 gene expression and lipid uptake in macrophages, showing its ability to
      antagonize CD36 pathways in vivo. These results demonstrate that SAB is an
      effective CD36 antagonist and suggest SAB as a potential anti-atherosclerotic
      agent.

PMID- 22658258
TI  - Weight change and lipoprotein particle concentration and particle size: a cohort
      study with 6.5-year follow-up.
AB  - OBJECTIVE: Obesity and overweight are related to unfavourable lipoprotein
      subclass profiles. Here we studied the relation between weight change and
      lipoprotein particle concentrations and sizes in a general population cohort in a
      longitudinal setting. METHODS: The cohort included 683 adults with a 6.5-year
      follow-up. Lipoprotein particle subclasses and mean particle sizes of VLDL, LDL,
      and HDL were measured by nuclear magnetic resonance spectroscopy. RESULTS: During
      the follow-up period, a weight loss of at least 5% was associated with decreased
      particle concentrations of all apoB-containing subclasses and increased
      concentrations of large HDL particles. Coherently, weight gain (>=5%) was
      associated with increases in all apoB-containing subclasses and decreases in
      total and medium HDL particle concentrations. The relatively largest increase
      occurred for large HDL particle concentration (24.1%, 95% CI 15.8-32.5) in weight
      loss and for large VLDL particle concentration (33.0%, 19.6-46.4) in weight gain.
      Weight change correlated positively with changes in apoB-containing lipoprotein
      particle concentrations and also with the change in average VLDL particle size.
      Negative correlations were found between weight change and the change in average
      LDL (r = -0.10) and HDL (r = -0.32) particle size, but not between weight change
      and total HDL particle concentration. CONCLUSION: Moderate weight loss is related
      to favourable and weight gain to unfavourable changes in lipoprotein subclass
      profiles. These population level findings underline the importance of weight
      control as a modifier of cardiovascular risk factors.

PMID- 22658259
TI  - Protection against vascular aging in Nox2-deficient mice: Impact on endothelial
      progenitor cells and reparative neovascularization.
AB  - BACKGROUND: Aging is associated with increased oxidative stress levels and
      impaired neovascularization following ischemia. Because Nox2-containing NADPH
      oxidase is a major source of ROS in the vasculature, we investigated its
      potential role for the modulation of ischemia-induced neovascularization in the
      context of aging. METHODS AND RESULTS: Hindlimb ischemia was surgically induced
      by femoral artery removal in young (2 months) and old (10 months) Nox2-deficient
      (Nox2(-/-)) and wild type mice. We found that Nox2 expression is increased by
      aging in ischemic muscles of wild type mice. This is associated with a
      significant reduction of blood flow recovery after ischemia in old compared to
      young mice at day 21 after surgery (Doppler flow ratios: 0.51 +/- 0.05 vs. 0.72
      +/- 0.05; p < 0.05). We also demonstrate that capillary and arteriolar densities
      are significantly reduced in ischemic muscles of old animals, while oxidative
      stress levels are increased (nitrotyrosine immunostaining). Importantly, Nox2
      deficiency reduces oxidative stress levels in ischemic tissues and restores blood
      flow recuperation and vascular densities in old animals. Endothelial progenitor
      cells (EPCs) have an important role for postnatal neovascularization. Here we
      show that the functional activities of EPCs (migration, adhesion to mature
      endothelial cells) are significantly impaired in old compared to young mice.
      However, Nox2 deficiency rescues EPC functional activities in old animals. We
      also demonstrate an age-dependent pathological increase of oxidative stress
      levels in EPCs (DHE, DCF-DA) that is not present in Nox2-deficient animals.
      CONCLUSION: Nox2-containing NADPH oxidase deficiency protects against age
      dependent impairment of neovascularization. Potential mechanisms include reduced
      ROS generation in ischemic tissues and preserved angiogenic activities of EPCs.

PMID- 22658260
TI  - Effect of aortic taper on patterns of blood flow and wall shear stress in
      rabbits: association with age.
AB  - OBJECTIVE: The distribution of atherosclerotic lesions changes with age in human
      and rabbit aortas. We investigated if this can be explained by changes in
      patterns of blood flow and wall shear stress. METHODS: The luminal geometry of
      thoracic aortas from immature and mature rabbits was obtained by micro-CT of
      vascular corrosion casts. Blood flow was computed and average maps of wall shear
      stress were derived. RESULTS: The branch anatomy of the aortic arch varied widely
      between animals. Wall shear was increased downstream and to a lesser extent
      upstream of intercostal branch ostia, and a stripe of high shear was located on
      the dorsal descending aortic wall. The stripe was associated with two vortices
      generated by aortic arch curvature; their persistence into the descending aorta
      depended on aortic taper and was more pronounced in mature geometries. These
      results were not sensitive to the modelling assumptions. CONCLUSIONS: Blood flow
      characteristics in the rabbit aorta were affected by the degree of taper, which
      tends to increase with age in the aortic arch and strengthens secondary flows
      into the descending aorta. Previously-observed lesion distributions correlated
      better with high than low shear, and age-related changes around branch ostia were
      not explained by the flow patterns.

PMID- 22658262
TI  - Educating for mindful perspectives on aging.

PMID- 22658261
TI  - Reduced alpha-lipoic acid synthase gene expression exacerbates atherosclerosis in
      diabetic apolipoprotein E-deficient mice.
AB  - OBJECTIVES: To study the effects of reduced lipoic acid gene expression on
      diabetic atherosclerosis in apolipoprotein E null mice (Apoe(-/-)). METHODS AND
      RESULTS: Heterozygous lipoic acid synthase gene knockout mice (Lias(+/-)) crossed
      with Apoe(-/-) mice were used to evaluate the diabetic effect induced by
      streptozotocin on atherosclerosis in the aortic sinus of the heart. While
      diabetes markedly increased atherosclerotic plaque size in Apoe(-/-) mice, a
      small but significant effect of reduced expression of lipoic acid gene was
      observed in diabetic Lias(+/-)Apoe(-/-) mice. In the aortic lesion area, the
      Lias(+/-)Apoe(-/-) mice exhibited significantly increased macrophage accumulation
      and cellular apoptosis than diabetic Lias(+/+)Apoe(-/-) littermates. Plasma
      glucose, cholesterol, and interleukin-6 were also higher. These abnormalities
      were accompanied with increased oxidative stress including a decreased ratio of
      reduced glutathione/oxidized glutathione in erythrocytes, increased systemic
      lipid peroxidation, and increased Gpx1 and MCP1 gene expression in the aorta.
      CONCLUSIONS: Decreased endogenous lipoic acid gene expression plays a role in
      development of diabetic atherosclerosis. These findings extend our understanding
      of the role of antioxidant in diabetic atherosclerosis.

PMID- 22658263
TI  - Case studies for an accelerated Bachelor of Science in Nursing pathophysiology
      course.

PMID- 22658264
TI  - Learning to think like a professional nurse: a critical questions strategy.

PMID- 22658265
TI  - A comparative evaluation of different treatment modalities for parasymphysis
      fractures: a pilot study.
AB  - Maxime Champy advised the use of two miniplates for parasymphysis fractures
      because of the high torsional forces in the anterior region of the mandible.
      According to him there is no need for intraoperative or postoperative
      intermaxillary fixation, but most surgeons use arch bars for intraoperative or
      postoperative intermaxillary fixation. This study evaluated the role of the lower
      arch bar as a tension band eliminating the need for an upper miniplate (tension
      band plate) in cases of parasymphysis fractures. 3 groups underwent treatment. In
      the first group, two titanium miniplates were placed across the fracture site
      along with Erich's arch bar for 6 weeks. In the second group, two titanium
      miniplates were used for osteosynthesis without Erich's arch bar. In the third
      group, one titanium miniplate was placed along with Erich's arch bar for 6 weeks.
      The results of third group were statistically non-significant compared with those
      of the first and second groups.

PMID- 22658267
TI  - Segmental osteotomy with interpositional bone grafting in the posterior maxillary
      region.
AB  - Tooth loss is followed by a natural bone resorption process that often leads to
      defects in the alveolar ridge, making the installation of dental implants
      unfeasible. Correction of such bone defects, especially loss of height of the
      ridge or associated loss of thickness, is a great challenge to dental surgeons.
      The technique of segmental osteotomy accompanied by interpositional bone grafting
      has been shown to be a viable option for addressing the problem. This report
      describes a successful application of the technique in the treatment of vertical
      dimension deficiency in the posterior maxillary region. Four months after graft
      surgery, 3 implants were successfully placed in accordance with the original
      reverse planning.

PMID- 22658266
TI  - Hypermobility and trauma as etiologic factors in patients with disc derangements
      of the temporomandibular joint.
AB  - The aim of the study was to investigate patients with temporomandibular joint
      (TMJ) disc derangement with its two clinical variants reciprocal clicking (RC)
      and chronic closed lock (CCL) with regard to the etiologic factors, previous jaw
      trauma and general (GJH) and local joint hypermobility (LJH). 42 patients (21
      with RC and 21 with CCL) and 20 control individuals were studied. The patients
      and controls were asked whether they had sustained any jaw trauma in the past and
      were then examined for the presence of GJH and LJH, using defined criteria.
      Patient and control groups were compared. Statistical evaluation included chi(2)
      test and paired Student's t test. Odds ratio was calculated in order to assess
      the relative risk of developing RC and CCL when the etiological factor was
      present. The results showed a significant association between RC and GJH (OR=9.6,
      p=0.0010) as well as LJH (OR=38, p=0.0001). CCL was clearly associated with GJH
      (OR=7.5, p=0.0030) while its association with LJH was not significant (OR=9.5,
      p=0.0582). No significant association with previous trauma was found. The results
      indicate that GJH is an important etiologic factor for the development of RC and
      CCL of the TMJ.

PMID- 22658268
TI  - Osteopathic manipulative treatment in obese patients with chronic low back pain:
      a pilot study.
AB  - BACKGROUND: Obesity is frequently associated with various musculoskeletal
      disorders including chronic low back pain (cLBP). Osteopathy is a discipline
      emphasizing the conservative treatment of the disease in an olistic vision. We
      designed a randomized controlled study to investigate whether Osteopathic
      Manipulative Treatment (OMT) combined with specific exercises (SE) is more
      effective than SE alone in obese patients with cLBP. METHODS: nineteen obese
      females with cLBP, randomized into 2 groups: SE + OMT and SE were studied during
      the forward flexion of the spine using an optoelectronic system. A biomechanical
      model was developed in order to analyse kinematics and define angles of clinical
      interest. OUTCOME MEASURES: kinematic of the thoracic and lumbar spine and pelvis
      during forward flexion, pain according to a visual analogue scale (VAS), Roland
      Morris Disability Questionnaire and Oswestry Low Back Pain Disability
      Questionnaire. RESULTS: significant effects on kinematics were reported only for
      OMT + SE with an improvement in thoracic range of motion of nearly 20%. All
      scores of the clinical scales used improved significantly. The greatest
      improvements occurred in the OMT + SE group. CONCLUSIONS: combined rehabilitation
      treatment including Osteopathic Manipulative Treatment (OMT + SE) showed to be
      effective in improving biomechanical parameters of the thoracic spine in obese
      patients with cLBP. Such results are to be attributed to OMT, since they were not
      evident in the SE group. We also observed a reduction of disability and pain. The
      clinical results should be considered preliminary due to the small sample size.

PMID- 22658269
TI  - Fractional vaporization of tissue with an oscillatory array of high temperature
      rods: part I: ex vivo study.
AB  - BACKGROUND: Short pulse duration (~0.1-5 milliseconds) CO2 lasers are perceived
      as excellent tools for vaporization of craters arrays in fractional skin
      resurfacing. OBJECTIVES: To present a thermo-mechanical ablation technology,
      which affects tissue identically to fractional CO2 lasers, however at a fraction
      of the size and cost of a laser. MATERIAL AND METHODS: The new technology is
      based on heating an oscillating array of thin metallic rods to a temperature of
      400 degrees C and advancing the rods into tissue down to a precise pre-selected
      depth for a duration of 0.1-5 milliseconds. As a result, an array of crater is
      vaporized with identical properties of those produced by CO2 lasers. An ex vivo
      test was performed with a thermo- metallic rod array prototype. RESULTS: Arrays
      of 10 * 10 vaporized micro-craters of 350 micron diameter, 200 micron depth have
      been produced with lateral thermal damage of 80 micron while thermal damage below
      craters was 80-250 micron. CONCLUSIONS: A resonating thermo-mechanical array of
      high temperature (350-400 degrees C) rods is capable of producing an array of
      craters identical to those produced with pulsed CO2 lasers.

PMID- 22658270
TI  - On the generalised embodiment of pain: how interoceptive sensitivity modulates
      cutaneous pain perception.
AB  - Individual differences in interoceptive sensitivity are associated with
      differences in reported intensity of emotional experience, vulnerability to
      anxiety and mood disorder and capacity for emotional self-regulation. Enhanced
      sensitivity to autonomic state is often accompanied by increased autonomic
      reactivity. Here we tested the hypothesis that healthy people classified as more
      interoceptively sensitive, by their performance of a heartbeat monitoring task,
      will demonstrate enhanced perception of pain. We further explored whether this
      effect is associated with a greater physiological reactivity to the pain stimuli.
      Using an algometer, cutaneous pressure pain was applied to the thenar eminence in
      60 healthy participants. Heart rate variability and respiratory activity were
      recorded concurrently. We observed significant relationships between heightened
      interoceptive sensitivity and both enhanced sensitivity and decreased tolerance
      to pain. These effects were accompanied by a more pronounced parasympathetic
      decrease and a change in sympathovagal balance during pain assessment in the
      high, compared to the low, interoceptively sensitive group. Our study provides
      novel evidence that interoceptive sensitivity is associated with the experience
      and tolerability of pain in conjunction with reactive changes in autonomic
      balance.

PMID- 22658271
TI  - Remember, remember.... a child's pain experience.

PMID- 22658272
TI  - The paradox of less sensation and more pain.

PMID- 22658273
TI  - The clinical significance of the atrial subendocardial smooth muscle layer and
      cardiac myofibroblasts in human atrial tissue with valvular atrial fibrillation.
AB  - BACKGROUND: The existence of myofibroblasts (MFBs) and the role of subendocardial
      smooth muscle (SSM) layer of human atrial tissue in atrial fibrillation (AF) have
      not yet been elucidated. We hypothesized that the SSM layer and MFB play some
      roles in atrial structural remodeling and maintenance of valvular AF in patients
      who undergo cardiac surgery. METHODS: We analyzed immunohistochemical staining of
      left atrial (LA) appendage tissues taken from 17 patients with AF and 15 patients
      remaining in sinus rhythm (SR) who underwent cardiac surgery (male 50.0%, 54.1 +/
      14.2 years old, valve surgery 87.5%). SSM was quantified by alpha-smooth muscle
      actin (alpha-SMA) stain excluding vascular structure. MFB was defined as alpha
      SMA+ cells with disorganized Connexin 43-positive gap junctions in Sirius red
      positive fibrotic area. RESULTS: The SSM layer of atrium was significantly
      thicker in patients with AF than in those with SR (P=.0091). Patients with SSM
      layer >= 14 MUm had a larger LA size (P=.0006) and greater fibrotic area
      (P=.0094) than those patients whose SSM layer <14 MUm. MFBs were found in 7 of 17
      (41.2%) patients with AF and 2 of 15 (13.3%) in SR group (P=.0456) in SSM area,
      colocalized with Periodic Acid-Schiff (PAS) stain-positive glycogen storage cells
      (95.5%). CONCLUSION: SSM layer was closely related to the existence of AF,
      degrees of atrial remodeling, and fibrosis in patients who underwent open heart
      surgery. We found that MFB does exist in SSM layer of human atrial tissue co
      localized with PAS-positive cells.

PMID- 22658274
TI  - Distal esophageal carcinomas in Chinese patients vary widely in histopathology,
      but adenocarcinomas remain rare.
AB  - In Western countries, distal esophageal adenocarcinoma has outnumbered squamous
      cell carcinoma because of a dramatic increase in the prevalence of columnar-lined
      esophagus. Because the relative prevalence of these diseases remains unknown in
      China, we investigated the histopathology of distal esophageal neoplasm in
      resection specimens from a high-volume medical center in China. A computerized
      search of esophageal cancer was conducted in the pathology database between 2004
      and 2010. Cancers with epicenter located within 5 cm above the gastroesophageal
      junction were retained for analysis. Pathology reports were reviewed along with
      medical, radiologic, and endoscopic records. All histology slides of selected
      cases were reevaluated (median, 13 per case). Conventional and basaloid squamous
      cell, adenosquamous, mucoepidermoid, and neuroendocrine carcinomas and esophageal
      adenocarcinoma were categorized according to the World Health Organization
      classification of esophageal cancers. The presence of columnar-lined esophagus
      and other pathologic changes were assessed in cases with residual esophageal
      mucosa. Among 1101 resections, 204 (19%) qualified for the study. Conventional
      and basaloid squamous cell, adenosquamous, mucoepidermoid, and neuroendocrine
      carcinomas and esophageal adenocarcinoma represented 76%, 11%, 3%, 2%, 6%, and 1%
      of the cases, respectively. Synchronous carcinomas were found in 12% and
      consisted of primarily squamous cell carcinoma (50%) and proximal gastric
      adenocarcinoma (38%). Columnar-lined esophagus was detected in 18% of the cases,
      among which intestinal metaplasia was present in 30% and low-grade dysplasia in
      7%. In conclusion, distal esophageal carcinomas in Chinese patients showed a wide
      histopathologic spectrum with predominant squamous cell carcinoma and rare
      esophageal adenocarcinoma. Although common, columnar-lined esophagus appears
      pathogenetically insignificant for most distal esophageal carcinomas.

PMID- 22658275
TI  - Application of molecular techniques in the diagnosis, prognosis and management of
      patients with colorectal cancer: a practical approach.
AB  - There has been an increasing role for molecular diagnostics in the diagnosis and
      management of cancer, and colorectal carcinoma is no exception. Recent molecular
      advances have elucidated 3 broad molecular subtypes of colorectal cancer,
      including chromosomal instability, microsatellite instability, and cytosine
      phosphoguanine island methylator phenotype, which will be discussed. Also, the
      common syndromes associated with colorectal carcinoma will be reviewed with a
      focus on the differentiation between Lynch syndrome and microsatellite unstable
      tumors. Molecular biomarkers for predictive and prognostic markers are also
      becoming widely used, and due to the clinical use of monoclonal antibodies to the
      epidermal growth factor receptor, an emphasis is placed on that pathway.

PMID- 22658276
TI  - Multiplex high-throughput gene mutation analysis in acute myeloid leukemia.
AB  - Classification of acute myeloid leukemia increasingly depends on genetic
      analysis. However, the number of known mutations in acute myeloid leukemia is
      expanding rapidly. Therefore, we tested a high-throughput screening method for
      acute myeloid leukemia mutation analysis using a multiplex mass spectrometry
      based approach. To our knowledge, this is the first reported application of this
      approach to genotype leukemias in a clinical setting. One hundred seven acute
      myeloid leukemia cases were screened for mutations using a panel that covers 344
      point mutations across 31 genes known to be associated with leukemia. The
      analysis was performed by multiplex polymerase chain reaction for mutations in
      genes of interest followed by primer extension reactions. Products were analyzed
      on a Sequenom MassARRAY system (San Diego, CA). The multiplex panel yielded
      mutations in 58% of acute myeloid leukemia cases with normal cytogenetics and 21%
      of cases with abnormal cytogenetics. Cytogenetics and routine polymerase chain
      reaction-based screening of NPM1, CEBPA, FLT3-ITD, and KIT was also performed on
      a subset of cases. When combined with the results of these standard polymerase
      chain reaction-based tests, the mutation frequency reached 78% in cases with
      normal cytogenetics. Of these, 42% harbored multiple mutations primarily
      involving NPM1 with NRAS, KRAS, CEBPA, PTPN11, IDH1, or FLT3. In contrast, cases
      with abnormal cytogenetics rarely harbored more than 1 mutation (1.5%),
      suggesting different underlying biology. This study demonstrates the feasibility
      and utility of broad-based mutation profiling of acute myeloid leukemia in a
      clinical setting. This approach will be helpful in defining prognostic subgroups
      of acute myeloid leukemia and contribute to the selection of patients for
      enrollment into trials with novel inhibitors.

PMID- 22658277
TI  - Approaching heterogeneity of human epidermal growth factor receptor 2 in surgical
      specimens of gastric cancer.
AB  - Gastric cancer shows intratumoral heterogeneity for human epidermal growth factor
      receptor 2 expression. We evaluated whether the number of tissue blocks analyzed
      or the antibodies used may influence the immunohistochemical results in
      gastrectomy specimens. Clinicopathologic data from 148 patients receiving gastric
      surgery for cancer were collected. One tissue block for each of 88 primary tumors
      and 60 paired primary tumors and metastases was examined for human epidermal
      growth factor receptor 2 status by immunohistochemistry using 3 different
      antibodies (HercepTest, CB11, and 4B5) and by fluorescent in situ hybridization.
      Two additional tissue blocks of the primary tumor were tested by
      immunohistochemistry if the results were negative on the first tissue block. The
      concordance among the 3 antibodies was 94.5% (testing 1 tissue block). Two cases
      showed a clinically significant discrepancy between primary tumor (score 0) and
      lymph nodes metastases (score 3+). Additional block analysis increased both the
      sensitivity (from 63% to 83%) and the accuracy (from 91% to 94%) of
      immunohistochemistry as compared with fluorescent in situ hybridization. The
      multiblock approach could potentially identify a greater number of human
      epidermal growth factor receptor 2-positive gastric cancers, particularly those
      with higher levels of intratumor heterogeneity. In turn, human epidermal growth
      factor receptor 2 positivity correlated with a worse prognosis (P=.011) and was
      an independent variable in multivariate analysis (hazard ratio, 1.57). In
      conclusion, testing more than 1 tissue block of cancer from specimens of gastric
      resection provides a more reliable human epidermal growth factor receptor 2
      assessment regardless of the antibody used.

PMID- 22658278
TI  - Subclinical hypertensive heart disease in black patients with elevated blood
      pressure in an inner-city emergency department.
AB  - STUDY OBJECTIVE: We examine the point prevalence of subclinical hypertensive
      heart disease in a cohort of urban emergency department (ED) patients with
      elevated blood pressure. METHODS: A convenience sample of hypertensive (blood
      pressure >= 140/90 mm Hg on 2 measurements) patients aged 35 years or older with
      no history of cardiac or renal disease who presented to a single urban ED and
      were asymptomatic from a cardiovascular perspective (ie, no symptoms of dyspnea
      or chest pain) were enrolled. All patients underwent a standardized evaluation
      (including echocardiography), and subclinical hypertensive heart disease was
      defined by the presence of one or more of the following criterion-based
      echocardiographic [corrected] findings: left-ventricular hypertrophy, systolic
      dysfunction, or diastolic dysfunction. RESULTS: A total of 161 patients were
      included. Mean age was 49.8 years (SD 8.3 years), 93.8% were black, and 51.6%
      were men. Nearly all (93.8%) had a history of hypertension, and many (68.3%) were
      receiving antihypertensive therapy at baseline. Mean systolic and diastolic blood
      pressures were 183.9 mm Hg (SD 25.1 mm Hg) and 109.5 mm Hg (SD 14.4 mm Hg),
      respectively. Subclinical hypertensive heart disease was found in 146 patients
      (90.7%; 95% confidence interval [CI] 85.2% to 94.3%), with most (n=131)
      displaying evidence of diastolic dysfunction (89.7%; 95% CI 83.7% to 93.7%). Left
      ventricular hypertrophy was also common (n=89; 61.0%; 95% CI 52.9% to 68.5%) and
      was often (but not exclusively) present in those with diastolic filling
      abnormalities (n=75; 57.3%; 95% CI 48.7% to 65.4%). CONCLUSION: In our largely
      black cohort of ED patients with elevated blood pressure, subclinical
      hypertensive heart disease was highly prevalent, suggesting the need for
      coordinated efforts to reduce cardiac consequences of hypertension in such inner
      city communities.

PMID- 22658279
TI  - A feasible shortcut for the mobilization outcome: Steady state CD34 positive
      hematopoietic stem cells.
AB  - Predicting success of hematopoietic cell mobilization is an important issue for
      transplant physicians. We examined the steady state peripheral blood CD34+ cell
      count to predict ability to mobilize adequate hematopoietic progenitor cells in
      63 myeloma and lymphoma patients. The median steady state CD34+ cell number was
      1.56/MUL (0.03-5.76). Although counting steady state CD34+ is definitely cost
      effective to predict the successful mobilization, we could not find a threshold
      steady state CD34 count of any value predicting successful mobilization.

PMID- 22658280
TI  - Lung infections: the radiologist's perspective.
AB  - Imaging plays a key role in lung infections. A CT scan must be carried out when
      there is a strong clinical suspicion of pneumonia that is accompanied by normal,
      ambiguous, or nonspecific radiography, a scenario that occurs most commonly in
      immunocompromised patients. CT allows clinicians to detect associated
      abnormalities or an underlying condition and it can guide bronchoalveolar lavage
      or a percutaneous or transbronchial lung biopsy. An organism can vary in how it
      is expressed depending on the extent to which the patient is immunocompromised.
      This is seen in tuberculosis in patients with AIDS. The infective agents vary
      with the type of immune deficiency and some infections can quickly become life
      threatening. Clinicians should be aware of the complex radiological spectrum of
      pulmonary aspergillosis, given that this diagnosis must be considered in specific
      settings.

PMID- 22658281
TI  - Secondary metabolites from a marine-derived fungus Aspergillus carneus Blochwitz.
AB  - Prenylated indole alkaloids, carneamides A-C (1-3), quinazolinone derivatives,
      carnequinazolines A-C (5-7), aryl C-glycosides, carnemycin A, B (8, 9) and a
      drimane sesquiterpenoid (10), together with known compounds (11-21) were isolated
      from the marine-derived fungus Aspergillus carneus (Trichocomaceae) KMM 4638. The
      antimicrobial and cytotoxic activities of the several alkaloids were examined.

PMID- 22658282
TI  - Unusual terpenylated acylphloroglucinols from Dryopteris wallichiana.
AB  - Four unusual terpenylated acylphloroglucinols were isolated from the diethyl
      ether extract of the scales and rhizomes of the fern Dryopteris wallichiana
      together with the known compounds albaspidins AA and AB, and filixic acids ABA
      and ABB. Structures of the isolated compounds were established by extensive
      spectroscopic analysis and their absolute configuration at C-14" was determined
      by comparing their CD spectra with those simulated for the respective isomers.
      Pure acylphloroglucinols displayed moderate in vitro nematocidal activity against
      L4 stage larvae of Nippostrongylus brasiliensis (LD50=22-121 MUM).

PMID- 22658283
TI  - [Prevention of Neonatal Group B Sreptococcal Infection. Spanish Recommendations.
      Update 2012. SEIMC/SEGO/SEN/SEQ/SEMFYC Consensus Document].
AB  - Group B streptococci (GBS) remain the most common cause of early onset neonatal
      sepsis. In 2003 the Spanish Societies of Obstetrics and Gynaecology, Neonatology,
      Infectious Diseases and Clinical Microbiology, Chemotherapy, and Family and
      Community Medicine published updated recommendations for the prevention of early
      onset neonatal GBS infection. It was recommended to study all pregnant women at
      35-37 weeks gestation to determine whether they were colonised by GBS, and to
      administer intrapartum antibiotic prophylaxis (IAP) to all colonised women. There
      has been a significant reduction in neonatal GBS infection in Spain following the
      widespread application of IAP. Today most cases of early onset GBS neonatal
      infection are due to false negative results in detecting GBS, to the lack of
      communication between laboratories and obstetric units, and to failures in
      implementing the prevention protocol. In 2010, new recommendations were published
      by the CDC, and this fact, together with the new knowledge and experience
      available, has led to the publishing of these new recommendations. The main
      changes in these revised recommendations include: microbiological methods to
      identify pregnant GBS carriers and for testing GBS antibiotic sensitivity, and
      the antibiotics used for IAP are updated; The significance of the presence of GBS
      in urine, including criteria for the diagnosis of UTI and asymptomatic
      bacteriuria in pregnancy are clarified; IAP in preterm labour and premature
      rupture of membranes, and the management of the newborn in relation to GBS
      carrier status of the mother are also revised. These recommendations are only
      addressed to the prevention of GBS early neonatal infection, are not effective
      against late neonatal infection.

PMID- 22658284
TI  - High-risk drug-use practices among a large sample of Australian prisoners.
AB  - BACKGROUND: Drug injection in prison is associated with a high risk of
      transmission of blood-borne pathogens including hepatitis C (HCV). The aim of
      this study was to estimate the prevalence and identify independent correlates of
      recent in-prison injecting drug use (P-IDU) among a large sample of adult
      prisoners in Queensland, Australia. METHODS: Confidential, structured interviews
      with 1,322 adult prisoners in Queensland, Australia. Prevalence estimates were
      corrected for sampling bias using inverse probability weighting. Independent
      correlates of recent P-IDU were identified using multivariable Poisson regression
      with backwards elimination. RESULTS: We estimated that among all adult prisoners
      in Queensland, Australia, the prevalence of lifetime IDU was 55.1%, of lifetime P
      IDU 23.0%, and of recent (during current sentence) P-IDU 13.2%. Significant,
      independent correlates of recent P-IDU included male gender (ARR=3.07, 95% CI
      1.83-5.12), being unemployed prior to incarceration (ARR=1.34, 95% CI 1.01-1.76),
      use of three or more drug types prior to incarceration (ARR=1.80, 95% CI 1.40
      2.31), a history of needle/syringe sharing (ARR=5.00, 95% CI 3.06-8.16),
      receiving a tattoo during the current prison sentence (ARR=2.19, 95% CI 1.67
      2.86) and HCV exposure (ARR=1.47, 95% CI 1.08-2.02). Older age was protective
      (ARR=0.90 per 5 years older, 95% CI 0.83-0.99). CONCLUSION: Drug injection in
      prison is common and, given the associations between in-prison drug injection and
      syringe sharing, unsafe tattooing and HCV exposure, poses a risk to both prisoner
      health and public health. There remains an urgent need to implement evidence
      based infection control measures, including needle and syringe programs, within
      prison settings.

PMID- 22658285
TI  - Mexican immigration to the US and alcohol and drug use opportunities: does it
      make a difference in alcohol and/or drug use?
AB  - BACKGROUND: Mexican immigrants in the US do not have increased risk for alcohol
      use or alcohol use disorders when compared to Mexicans living in Mexico, but they
      are at higher risk for drug use and drug use disorders. It has been suggested
      that both availability and social norms are associated with these findings. We
      aimed to study whether the opportunity for alcohol and drug use, an indirect
      measure of substance availability, determines differences in first substance use
      among people of Mexican origin in both the US and Mexico, accounting for gender
      and age of immigration. METHODS: Data come from nationally representative surveys
      in the United States (2001-2003) and Mexico (2001-2002) (combined n=3432). We
      used discrete time proportional hazards event history models to account for time
      varying and time-invariant characteristics. The reference group was Mexicans
      living in Mexico without migration experience. RESULTS: Female immigrants were at
      lower risk of having opportunities to use alcohol if they immigrated after the
      age of 13, but at higher risk if they immigrated prior to this age. Male
      immigrants showed no differences in opportunity to use alcohol or alcohol use
      after having the opportunity. Immigration was associated with having drugs
      opportunities for both sexes, with larger risk among females. Migration was also
      associated with greater risk of using drugs after having the opportunity, but
      only significantly for males. CONCLUSIONS: The impacts of immigration on
      substance use opportunities are more important for drugs than alcohol. Public
      health messages and educational efforts should heed this distinction.

PMID- 22658286
TI  - Rationale for use of the Clinical Dementia Rating Sum of Boxes as a primary
      outcome measure for Alzheimer's disease clinical trials.
AB  - BACKGROUND: We used the database of the Alzheimer's Disease Neuroimaging
      Initiative (ADNI) to explore the psychometric properties of the Clinical Dementia
      Rating Sum of Boxes (CDR-SB) to consider its utility as an outcome measure for
      clinical trials in early and mild, as well as later, stages of Alzheimer's
      disease (AD). METHODS: We assessed internal consistency, structural validity,
      convergent validity, and 2-year internal and external responsiveness of the CDR
      SB using data from 382 subjects with early or mild AD at entry into the ADNI
      study. RESULTS: The CDR-SB assesses both cognitive and functional domains of AD
      disability. Mean scores declined nearly linearly; CDR-SB cognitive and functional
      subsums contributed equally to total scores at both very mild (early) and mild
      stages of the disease. CONCLUSIONS: The CDR-SB has psychometric properties that
      make it attractive as a primary outcome measure that comprehensively assesses
      both cognitive and functional disability in AD patients. It may prove
      particularly useful for studies in early, predementia stages of AD.

PMID- 22658287
TI  - Comparison of two fall risk assessment tools (FRATs) targeting falls prevention
      in sub-acute care.
AB  - FRATs are designed to identify both persons at high risk of falls and to allow
      for cost-effective targeting of fall prevention strategies. This study compares
      two FRATs (BHS FRAT and TNH-STRATIFY) for accuracy of predicting falls and
      targeting of fall prevention strategies in a sub-acute hospital. Comparisons of
      retrospective audit data over two periods (use of the BHS-FRAT; post TNH-STRATIFY
      implementation) were used in the evaluation (n=362). Inter-rater reliability of
      the TNH-STRATIFY was evaluated from independent assessment by two nurses for 30
      sub-acute patients and using intraclass correlation coefficient (ICC(2,1)). Event
      rate (ER) and standard measures of predictive accuracy were calculated for both
      FRATs. The proportions of patients with documented fall prevention strategies
      addressing identified fall risk factors were compared between audit phases. The
      TNH-STRATIFY had high inter-rater reliability (ICC(2,1)=0.96). The BHS-FRAT and
      TNH-STRATIFY demonstrated poor predictive accuracy using recommended high risk
      cut-off scores, with low specificity(ER) (0.07 and 0.13 respectively) and very
      low Youden Index(ER) (0.04 and 0.07 respectively), although these measures
      improved using modified cut-off scores. Positive and negative predictive values
      were moderate for the BHS-FRAT (0.51, 0.64) and TNH-STRATIFY (0.52, 0.61). The
      falls rate and proportion of recurrent fallers did not change between audit
      phases. Implementation rates for prevention strategies for key risk factors were
      higher following implementation of the TNH-STRATIFY. The results indicated that
      the TNH-STRATIFY, combined with associated nursing care plan falls documentation,
      improved the targeting of prevention strategies for key risk factors such as
      cognitive impairment, incontinence and mobility impairment.

PMID- 22658288
TI  - Computational methods for electron tomography.
AB  - Electron tomography (ET) has emerged as a powerful technique to address
      fundamental questions in molecular and cellular biology. It makes possible
      visualization of the molecular architecture of complex viruses, organelles and
      cells at a resolution of a few nanometres. In the last decade ET has allowed
      major breakthroughs that have provided exciting insights into a wide range of
      biological processes. In ET the biological sample is imaged with an electron
      microscope, and a series of images is taken from the sample at different views.
      Prior to imaging, the sample has to be specially prepared to withstand the
      conditions within the microscope. Subsequently, those images are processed and
      combined to yield the three-dimensional reconstruction or tomogram. Afterwards, a
      number of computational steps are necessary to facilitate the interpretation of
      the tomogram, such as noise reduction, segmentation and analysis of subvolumes.
      As the computational demands are huge in some of the stages, high performance
      computing (HPC) techniques are used to make the problem affordable in reasonable
      time. This article intends to comprehensively review the methods, technologies
      and tools involved in the different computational stages behind structural
      studies by ET, from image acquisition to interpretation of tomograms. The HPC
      techniques usually employed to cope with the computational demands are also
      briefly described.

PMID- 22658289
TI  - Does change talk during brief motivational interventions with young men predict
      change in alcohol use?
AB  - Client change talk (CT) during motivational interviewing and brief motivational
      interventions (BMIs) have been described as predictors of behavior change, but
      these links have not been clearly evaluated in research on young people. Within
      127 BMIs with 20-year-old men with at-risk alcohol consumption, each CT utterance
      was categorized and given a strength rating using the Motivational Interviewing
      Skill Code 2.1. Several ways of categorizing and measuring CT were tested using
      stepwise regression procedures. Overall CT measures were not significantly
      related to changes in drinking at 6-month follow-up. Regarding CT sub-dimensions,
      the frequency of ability/desire/need to change and of ability/desire/need not to
      change, as well as the average strength of ability/desire/need, predicted
      significant change in the expected direction. CT length was not significantly
      linked to outcome. The frequency and strength with which some CT sub-dimensions
      are expressed during BMI seemed to be important predictors of change in drinking
      among young men and might thus be especially important for clinicians to notice.

PMID- 22658291
TI  - Laboratory model for surgical drainage.

PMID- 22658290
TI  - Examining the temporal relationship between psychological climate, work attitude,
      and staff turnover.
AB  - Relative to the broader industrial-organizational (I-O) psychology field,
      research on the turnover of substance use disorder (SUD) treatment staff is in
      its infancy. Despite its long and rich history, recent reviews of the turnover
      literature within I-O psychology have noted that there remains considerable room
      for improvement. In particular, recommendations have been made for research that
      considers time in the turnover process and explores more distal causes of staff
      turnover. Addressing these gaps, this article examined the temporal relationship
      between latent measures of psychological climate, work attitude, and staff
      turnover. Using data from 95 SUD treatment staff clustered within 29 treatment
      organizations, multilevel discrete-time survival analyses revealed that a latent
      measure of work attitude (e.g., job satisfaction, pay satisfaction, turnover
      intentions) fully mediated the temporal relationship between latent measures of
      psychological climate (e.g., supervisor support, coworker support, role conflict)
      and subsequent staff turnover.

PMID- 22658292
TI  - Re: Racial disparities in outcomes after appendectomy for acute appendicitis.

PMID- 22658293
TI  - Clinical outcome of stable outpatients with coronary, cerebrovascular or
      peripheral artery disease, and atrial fibrillation.
AB  - BACKGROUND: The influence of atrial fibrillation (AF) on outcome in patients with
      symptomatic atherosclerotic disease has not been thoroughly studied. METHODS:
      FRENA is an ongoing registry of stable outpatients with coronary (CAD),
      cerebrovascular (CVD), or peripheral (PAD) artery disease. With the aim to guide
      therapy, we assessed the incidence of subsequent myocardial infarction (MI),
      ischemic stroke or major bleeding in patients with AF, according to initial
      presentation. RESULTS: As of June 2011, 3848 patients were recruited: 1436 had
      CAD, 1104 CVD, and 1308 had PAD. Of these, 470 (12%) had AF: 151 patients with
      CAD, 157 with CVD, and 162 with PAD. Over a mean follow-up of 16 +/- 13 months,
      19 patients with AF developed acute MI, 22 ischemic stroke and 7 bled. Among AF
      patients with CAD, the incidence of subsequent MI (5.00 events per 100 patient
      years; 95% CI: 2.54-8.91) was non-significantly higher than that of stroke (1.48;
      95% CI: 0.38-4.04) or major bleeding (1.47; 95% CI: 0.37-4.01). Among those with
      CVD, the incidence of stroke (5.61; 95% CI: 2.95-9.75) exceeded that of MI (no
      events) or major bleeding (0.51; 95% CI: 1.24-6.36). Among those with PAD, the
      incidence of MI (4.41; 95% CI: 2.15-8.10) and stroke (3.93; 95% CI: 1.82-7.46)
      were similar. CONCLUSIONS: CAD patients with AF are at a higher risk of
      subsequent MI than of stroke. Among those with CVD, the risk of stroke far
      exceeds that of MI. Those with PAD have a high and similar risk for both events.

PMID- 22658294
TI  - Studies on the mechanism of action of the aptamer BAX499, an inhibitor of tissue
      factor pathway inhibitor.
AB  - INTRODUCTION: Promoting thrombin generation by inhibiting tissue factor pathway
      inhibitor (TFPI) is a potentially viable therapeutic approach to the prevention
      and/or treatment of bleeding in hemophilia. In this report, we studied the
      interaction between an aptamer (BAX499; formerly ARC19499) and TFPI that resulted
      in inhibition of TFPI-mediated regulation of the tissue factor pathway. MATERIALS
      AND METHODS: Enzyme kinetic analyses were performed to study the interaction
      between BAX499 and recombinant TFPI against factor Xa, the extrinsic Xase and
      prothrombinase activities. Diluted prothrombin time assay was used to investigate
      the effects of BAX499 on factor VIII-deficient plasma collected from hemophilia
      patients. RESULTS: Our results indicate that after binding of BAX499 to TFPI, the
      TFPI/ BAX499 complex retains factor Xa inhibitory activity, albeit with reduced
      affinity. When tested in an extrinsic Xase activity assay, BAX499 delayed TFPI
      mediated inhibition of extrinsic Xase activity. In addition, BAX499 reversed TFPI
      inhibition of the prothrombinase complex. BAX499 shortened the dilute prothrombin
      time in factor VIII-deficient plasma, and when added to freshly drawn hemophilia
      A blood either with or without a factor VIII inhibitor, the whole blood clotting
      time was also shortened. These results suggest that BAX499 may be a useful
      addition to the armamentarium of bypassing agents to control bleeding in
      hemophilic patients with inhibitors.

PMID- 22658295
TI  - Potential of chiral anion-exchangers operated in various subcritical fluid
      chromatography modes for resolution of chiral acids.
AB  - Anion-exchange-type chiral stationary phases (CSPs) derived from quinine or
      quinidine were applied in subcritical fluid chromatography (SFC) for the direct
      separation of chiral acidic compounds. Employing subcritical (sc) mobile phase
      modes (CO2 + methanol as co-solvent and acids and bases as additives) first the
      influence of type and amount of acidic and basic additives on separation
      performance was investigated. Secondly, water was tested as a neutral additive
      and the influence of temperature variation on enantioselectivity was studied.
      Thirdly, we could chromatographically confirm that the often verbalized "inherent
      acidity" of sc CO2 + methanol is manifested by the in situ formation of
      methylcarbonic acids in the sc mobile phase and thus functioning as acidic
      additive. Accordingly the dissociated methylcarbonic acid, acting as a
      counterion, enables an anion exchange mechanism between the cationic CSP and the
      corresponding acidic analyte. In the absence of a dissociable acid in the mobile
      phase such an ion exchange mode would not work following a stoichiometric
      displacement model. This finding is further corroborated by the use of ammonia in
      methanol as co-solvent thus generating in situ the ammonium salt of
      methylcarbonic acid. In summary, we report on ion-exchange mediated
      chromatographic separations in SFC modes by merely using (i) sc CO2 and MeOH,
      (ii) sc CO2 and ammonia in MeOH, and (iii) sc CO2 and MeOH plus acids and bases
      as additives. Comparisons to HPLC mode have been undertaken to evaluate merits
      and limitations. This mode exhibits high potential for preparative chromatography
      of chiral acids combining pronounced enantioselectivity with high column
      loadability and avoiding possibly troublesome mobile phase additives, as the in
      situ formed methylcarbonic acid disintegrates to CO2 and methanol upon pressure
      release.

PMID- 22658296
TI  - Controlled synthesis and chiral recognition of immobilized cellulose and amylose
      tris(cyclohexylcarbamate)s/3-(triethoxysilyl)propylcarbamates as chiral packing
      materials for high-performance liquid chromatography.
AB  - The cyclohexylcarbamates of cellulose and amylose bearing a controlled amount of
      3-(triethoxysilyl)propyl residue were synthesized by a one-pot process and
      efficiently immobilized onto silica gel through the intermolecular
      polycondensation of triethoxysilyl group. Their chiral recognition abilities were
      evaluated as chiral packing materials (CPMs) for high-performance liquid
      chromatography (HPLC). The immobilized CPMs exhibited comparable or higher
      recognition abilities than the conventional coated-type CPMs. The universal
      solvent compatibility of the immobilized CPMs clearly contributes to the
      improvement of chiral recognition for most racemates used in the present study.
      Interestingly, a significantly improved resolution for racemic trans-stilbene
      oxide (alpha=2.23) could be attained on the immobilized CPM using the eluent
      containing 30 vol.% chloroform in hexane, which cannot be used for the
      conventional coated-type CPMs. On the CPMs, almost no resolution of trans
      stilbene oxide was attained by a typical eluent, hexane-2-propanol mixture
      (90/10, v/v). The novel immobilized CPM can also be used in thin-layer
      chromatography (TLC) due to the absence of an aromatic group.

PMID- 22658297
TI  - Unbiased metabolite profiling by liquid chromatography-quadrupole time-of-flight
      mass spectrometry and multivariate data analysis for herbal authentication:
      classification of seven Lonicera species flower buds.
AB  - Plant-based medicines become increasingly popular over the world. Authentication
      of herbal raw materials is important to ensure their safety and efficacy. Some
      herbs belonging to closely related species but differing in medicinal properties
      are difficult to be identified because of similar morphological and microscopic
      characteristics. Chromatographic fingerprinting is an alternative method to
      distinguish them. Existing approaches do not allow a comprehensive analysis for
      herbal authentication. We have now developed a strategy consisting of (1) full
      metabolic profiling of herbal medicines by rapid resolution liquid chromatography
      (RRLC) combined with quadrupole time-of-flight mass spectrometry (QTOF MS), (2)
      global analysis of non-targeted compounds by molecular feature extraction
      algorithm, (3) multivariate statistical analysis for classification and
      prediction, and (4) marker compounds characterization. This approach has provided
      a fast and unbiased comparative multivariate analysis of the metabolite
      composition of 33-batch samples covering seven Lonicera species. Individual
      metabolic profiles are performed at the level of molecular fragments without
      prior structural assignment. In the entire set, the obtained classifier for seven
      Lonicera species flower buds showed good prediction performance and a total of 82
      statistically different components were rapidly obtained by the strategy. The
      elemental compositions of discriminative metabolites were characterized by the
      accurate mass measurement of the pseudomolecular ions and their chemical types
      were assigned by the MS/MS spectra. The high-resolution, comprehensive and
      unbiased strategy for metabolite data analysis presented here is powerful and
      opens the new direction of authentication in herbal analysis.

PMID- 22658298
TI  - Preparation of aqueous two-phase systems composed of two pH-response polymers and
      liquid-liquid extraction of demeclocycline.
AB  - Aqueous two-phase systems have potential applications for separation and
      purification of bioproducts in bio-industry. However, a key problem is the
      recovery of the polymers forming aqueous two-phase systems. In this study, two
      novel random copolymers (P(ADB) and P(ADBA)) were synthesized using acrylic acid,
      dimethylamino-ethyl methacrylate, butyl methacrylate and allyl alcohol as
      monomers and used to form pH response aqueous two-phase systems. The recoveries
      of P(ADB) and P(ADBA) are 97.18% and 98.87% and the pI of P(ADB) and P(ADBA) are
      2.79 and 4.01, respectively. Demeclocycline was partitioned in the P(ADB)/P(ADBA)
      aqueous two-phase systems and the partition coefficient reached 0.085, in the
      presence of MgSO4 (60 mmol/L) at pH 5.28.

PMID- 22658299
TI  - The influence of the organic modifier in hydro-organic mobile phase on separation
      selectivity of steroid hormones separation using cholesterol-bonded stationary
      phases.
AB  - Chromatographic properties of four cholesterol bonded phases with different
      structures were studied. The columns used were packed with a stationary phase
      containing a cholesterol molecule attached to the silica surface using different
      types of linkage molecules. Columns were compared according to the retention and
      separation selectivity of steroid hormones. The measurements were done using
      binary hydro-organic mobile phases with methanol, ethanol and acetonitrile as an
      organic modifier. The presented results show that the coverage density of the
      bonded ligands and the type of organic modifier strongly influence the retention
      mechanism and separation selectivity of steroid hormones on cholesterol
      containing adsorbents.

PMID- 22658300
TI  - Factors influencing left atrial volume in treated hypertension.
AB  - BACKGROUND: Left atrial (LA) enlargement has been documented to occur in
      hypertension (HT), and has been an index for evaluating the diastolic function of
      the left ventricle. Enlargement of the LA is one of the vital factors that induce
      heart failure and atrial fibrillation (AF) in patients with HT. METHODS AND
      SUBJECTS: 130 treated hypertensive patients were enrolled. All recruits
      participated in an echocardiogram, electrocardiogram, a routine blood examination
      including brain natriuretic peptide (BNP), and physical examinations. RESULTS:
      Left ventricular mass (LVM) indexed to height(2.7) had a significant positive
      correlation with left atrial volume index (LAVI) (p<0.0001), as well as natural
      logarithm BNP (p<0.001). Blood pressure levels were not associated with LAVI,
      neither body mass index nor age. LAVI had a positive correlation with factors
      involving the left ventricle volume, LVM, and right ventricle systolic pressure
      (RVSP) (r=0.687, p<0.0001). The parameters of LV diastolic function were
      positively but weakly associated with LA size. In the subgroup of LAVI, the
      evidence of paroxysmal atrial fibrillation (PAF): LAVI<32 ml/m(2) had no PAF,
      whereas the incidence of PAF was 7.5%, 11.4%, and 15.2%, respectively in the
      LAVI>32 ml/m(2) group. Of anti-hypertension drugs, angiotensin-converting enzyme
      inhibitors and angiotensin receptor blockers had a tendency to reduce LAVI;
      however, there was no statistical significance within the groups. CONCLUSIONS:
      Left ventricular volume and mass are independent factors affecting LAVI in
      treated HT. The incidence of PAF is associated with LA size. In patients with
      treated HT, LA size may be a useful surrogate marker for monitoring the
      effectiveness of medical therapy and occurrence of AF.

PMID- 22658301
TI  - Treatment outcome of patients with stages I-II nasopharyngeal carcinoma after
      late course accelerated hyperfractionation radiotherapy alone.
AB  - OBJECTIVES: To follow up the efficacy and incidence of radiation-induced
      complications of late course accelerated fractionation (LCAF) radiotherapy in
      early-stage nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From December
      1995 to November 2002, 158 patients with stages I-II NPC were admitted for
      radiotherapy alone. For the first two-thirds of the treatment, 2 daily fractions
      of 1.2 Gy were given to the primary lesion, 5 days per week to a total dose of 48
      Gy/40 fractions, over a period of 4 weeks. From the 5th week, an accelerated
      hyperfractionation schedule was carried out. Two daily fractions of 1.5 Gy were
      given, to a total dose of 30 Gy/20 fractions over 2 weeks. Thus the total dose
      was 78 Gy in 60 fractions in 6 weeks. RESULTS: All patients completed the
      treatment. Acute mucositis: none in 3 patients, grade 1 in 32, grade 2 in 69,
      grade 3 in 51, and grade 4 in 3 patients. Five-year nasopharyngeal control and
      overall survival (OS) rate of T1 and T2 were 97.8%, 90.2% (p=0.380) and 88.6%,
      81.4% (p=0.252), respectively. Five-year OS in N0 and N1 patients were 86.5% and
      81.9% (p=0.033), respectively. Thirty-eight patients died, and the main cause of
      death was distant metastasis. Seventeen (11%) patients had radiation-induced
      cranial nerve palsy. CONCLUSION: With LCAF, treatment-related toxicities were
      acceptable. Five-year nasopharyngeal control and OS in T2 stage were improved.
      Main cause of death was distant metastasis. Patients with N1 had a relatively
      lower survival rate, which suggested that chemotherapy might be indicated for
      those patients.

PMID- 22658302
TI  - Female smokers show lower pain tolerance in a physical distress task.
AB  - Numerous studies have established a link between distress tolerance and smoking
      cessation outcomes. The present study examined whether smoking status affected
      physical distress tolerance, and considered this question separately for men and
      women. The sample was comprised of healthy adults, 56 smokers (63% male) and 58
      nonsmokers (62% female). The pain stimulus was a cold pressor task. Outcome
      variables were seconds immersed in cold water when pain was first reported
      (threshold), and total seconds immersed in cold water (tolerance). Participants
      verbally reported their pain rating on a 0-100 scale after the task, and then
      completed the McGill Pain Questionnaire-Short Form. Smokers displayed lower pain
      tolerance than nonsmokers (p=.045), and women displayed lower pain tolerance than
      men (p=.017). Female smokers had significantly lower pain tolerance than other
      groups (p=.001). There were no significant differences in pain threshold or pain
      perception by smoking status or gender (p>.05). Lower physical distress tolerance
      could place female smokers at risk for difficulty in quitting smoking. This
      population needs additional research to better understand their unique pain
      experience and how physical distress tolerance impacts their smoking cessation
      outcomes.

PMID- 22658303
TI  - Disparities in completion of substance abuse treatment among Latino subgroups in
      Los Angeles County, CA.
AB  - RATIONALE: A growing body of research has revealed disparities with respect to
      drug use patterns within Latino subgroups. However, the extent to which these
      potential disparities enable different Latino subgroups to respond favorably to
      treatment is unclear. METHODS: This study analyzed a subset of multicross
      sectional data (2006-2009) on Latinos collected from publicly funded facilities
      in Los Angeles County, CA (N=12,871). We used multilevel logistic regressions to
      examine individual and service-level factors associated with treatment completion
      among subgroups of first-time Latino treatment clients. RESULTS: Univariate
      analysis showed that Cubans and Puerto Ricans were less likely to complete
      treatment than Mexicans and other Latinos. Cubans and Puerto Ricans entered
      treatment at an older age and with higher formal education than Mexicans, yet
      they were more likely to report mental health issues and use of cocaine and
      heroin as primary drugs of choice respectively. Multivariate analysis showed that
      age, having mental health issues, reporting high use of drugs at intake, and use
      of methamphetamines and marijuana were associated with decreased odds of
      completing treatment among all Latino subgroups. In contrast, age at first drug
      use, treatment duration, and referral monitoring by the criminal system increased
      the odds of completing treatment for all members. CONCLUSION: These findings have
      implications for targeting interventions for members of different Latinos groups
      during their first treatment episode. Promising individual and service factors
      associated with treatment completion can inform the design of culturally specific
      recovery models that can be evaluated in small-scale randomized pilot studies.

PMID- 22658304
TI  - The contribution of emotion regulation difficulties to risky sexual behavior
      within a sample of patients in residential substance abuse treatment.
AB  - The present study examined the unique contribution of emotion regulation
      difficulties to past-year risky sexual behavior (RSB) among substance use
      disorder (SUD) patients (above and beyond other known RSB risk factors). A sample
      of 177 SUD patients completed a series of questionnaires. At the zero-order
      level, emotion regulation difficulties, were significantly positively associated
      with the number of commercial sexual (i.e., the exchange of sex for drugs or
      money) partners with which penetrative sex occurred and significantly negatively
      associated with the likelihood of using a condom when having sex with a
      commercial partner under the influence of drugs. Emotion regulation difficulties
      also significantly predicted these RSB indices above and beyond other RSB risk
      factors, including demographics, depression, sensation seeking, traumatic
      exposure, and substance use severity. The specific emotion regulation difficulty
      of lack of emotional clarity emerged as a unique predictor of RSB. The
      implications of these findings for understanding motivations for RSB and
      developing targeted interventions for RSB among SUD patients are discussed.

PMID- 22658305
TI  - Severity of anxiety in mental health versus addiction treatment settings when
      social anxiety and substance abuse are comorbid.
AB  - There is increasing interest in the co-occurrence of social anxiety and
      addiction. Each investigation has a specific vantage point, e.g., the effect
      social anxiety has in a population with addiction or that of addiction in a
      population with social anxiety, which could create unique findings. Among
      comorbid individuals, is social anxiety more severe in people seeking treatment
      for anxiety, as compared to those seeking treatment for addiction? This report
      compares social anxiety severity between subjects in two studies--one involving
      socially anxious individuals (n=38) seeking treatment for addictions; the other
      (n=41) subjects with social anxiety and an alcohol use disorder, seeking
      treatment for social anxiety. Baseline severity scores on the Liebowitz Social
      Anxiety Scale for social anxiety were compared between the groups. No significant
      differences were found. For both groups, social anxiety was largely in the severe
      range. The results suggest that clinicians should attend to social anxiety
      symptom severity in patients with co-occurring social anxiety and addiction,
      regardless of the condition for which treatment is sought.

PMID- 22658306
TI  - Neurological manifestations of TB-IRIS: a report of 4 children.
AB  - INTRODUCTION: Tuberculosis-associated immune reconstitution inflammatory syndrome
      (TB-IRIS) is a potentially life-threatening complication in HIV infected children
      with tuberculosis (TB) of the central nervous system. HIV-associated TB-IRIS has
      not been previously described in children with neurotuberculosis. OBJECTIVE: To
      describe the neurological and neuro-radiological features of 4 consecutive cases
      of TB-IRIS in children with neurotuberculosis and to discuss possible management
      strategies. RESULTS: Three patients treated for tuberculosis of the central
      nervous system experienced paradoxical worsening of neurological symptoms when
      combination antiretroviral therapy (cART) was initiated. Intracranial
      tuberculomas were unmasked in the 4th patient. All patients developed new
      neurological signs within 10 days of cART initiation. Neurological symptoms and
      signs included headache, seizures, meningeal irritation, decreased level of
      consciousness, ataxia and focal motor deficit. Interventions included the
      temporary discontinuation of cART and the use of corticosteroids in all patients.
      Three patients received thalidomide and 1 chloroquine and mycophenolate mofetil.
      One patient died and the others experienced prolonged hospitalization.
      CONCLUSION: TB-IRIS should be considered when new neurological signs develop
      shortly after initiation of cART in children. There is little data to guide the
      timing of initiation of cART and the management of complications in children.

PMID- 22658307
TI  - Feeding and communication impairments in infants with central grey matter lesions
      following perinatal hypoxic-ischaemic injury.
AB  - BACKGROUND: Basal ganglia and thalamic (BGT) injury is common after acute
      perinatal hypoxia-ischaemia. Cerebral palsy is the most obvious consequence of
      BGT injury affecting 70-75% of survivors and is predictable from neonatal
      magnetic resonance imaging (MRI). However there is no equivalent predictive data
      for other specific outcomes. Feeding and communication impairments are also
      common in children following hypoxic-ischaemic encephalopathy (HIE) and BGT
      injury. AIMS: To describe, in infants with HIE and BGT injury, the prevalence of
      feeding and communication impairments; and to evaluate the accuracy of early MRI
      for predicting these outcomes. METHODS: 175 term infants with HIE and BGT injury
      were studied. Brain lesions were classified by site and severity from the MRI
      scans. Motor, feeding and communication impairments were documented at 2 years.
      RESULTS: Feeding and communication impairments occurred in 65% and 82% of 126
      survivors respectively and related strongly to the severity of motor impairment.
      Forty-one children had a gastrostomy or long-term nasogastric tube. Injury
      severity in all brain regions was significantly associated with feeding and
      communication impairment on univariate analysis. On logistic regression analysis
      BGT (OR 10.9) and mesencephalic lesions (OR 3.7) were independently associated
      with feeding impairment; BGT (OR 10.5) and pontine lesions (OR 3.8) were
      associated with gastrostomy; the severity of BGT lesions (OR 20.1) was related to
      the severity of communication impairment. CONCLUSIONS: Feeding and communication
      impairment are very common in children with BGT and brainstem injury of neonatal
      origin and can be well predicted from early MRI scans.

PMID- 22658309
TI  - Comparison of temperature and moisture requirements for sporulation of
      Aspergillus flavus sclerotia on natural and artificial substrates.
AB  - A key step in the infection cycle by Aspergillus flavus in maize is sporulation
      of sclerotia present in soil or in crop debris. However, little information is
      available on this critical and important phase. This study included experiments
      on artificial (Czapek Dox Agar (CZ)) and natural (maize stalks) substrates under
      different conditions of temperature (T; from 5 to 45  degrees C) and water
      activity (a(w); from 0.50 to 0.99) levels to quantify sporulation from sclerotia.
      The mean numbers of spores were higher on defined nutritional medium in vitro on
      CZ agar than on maize stalks (4.5*10(6) spores/sclerotium versus 4.2*10(4)
      spores/sclerotium) with production initiated after 6 and 24h, respectively.
      Surprisingly, the optimal temperature was found at 30-35  degrees C for CZ agar
      (9.23*10(6) spores/sclerotium) and to be 20-25  degrees C for maize stalks
      (6.26*10(4) spores/sclerotium). Water stress imposition only reduced sporulation
      at <=0.90 a(w.) With more available water no significant differences were found
      between 0.90 and 0.99 a(w). This type of data is critical in the development of a
      mechanistic model to predict the infection cycle of A. flavus in maize in
      relation to meteorological conditions.

PMID- 22658310
TI  - Comparative virulence phenotypes and molecular genotypes of Puccinia striiformis
      f. sp. tritici, the wheat stripe rust pathogen in China and the United States.
AB  - Stripe rust (yellow rust) of wheat, caused by Puccinia striiformis f. sp.
      tritici, is one of the most important diseases in both China and the United
      States. The Chinese and US populations of the stripe rust fungus were compared
      for their virulence phenotypes on wheat cultivars used to differentiate races of
      the pathogen in China and the US and molecular genotypes using simple sequence
      repeat (SSR) markers. From 86 Chinese isolates, 54 races were identified based on
      reactions on the 17 Chinese differentials and 52 races were identified based on
      the 20 US differentials. The selected 51 US isolates, representing 50 races based
      on the US differentials, were identified as 41 races using the Chinese
      differentials. A total of 132 virulence phenotypes were identified from the 137
      isolates based on reactions on both Chinese and US differentials. None of the
      isolates from the two countries had identical virulence phenotypes on both sets
      of differentials. From the 137 isolates, SSR markers identified 102 genotypes, of
      which 71 from China and 31 from the US. The virulence data clustered the 137
      isolates into 20 virulence groups (VGs) and the marker data clustered the
      isolates into seven molecular groups (MGs). Virulence and SSR data had a low (r =
      0.34), but significant (P = 0.01) correlation. Principal component analyses using
      either the virulence data or the SSR data separated the isolates into three
      groups: group a consisting of only Chinese isolates, group b consisting of both
      Chinese and US isolates and group c consisting of mostly US isolates. A neighbour
      joining tree generated using the molecular data suggested that the P. striiformis
      f. sp. tritici populations of China and the US in general evolved independently.

PMID- 22658308
TI  - Evaluating objective and subjective quantitative parameters at the initial visit
      to predict future glaucomatous visual field progression.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the ability of structural assessment to
      predict glaucomatous visual field progression. PATIENTS AND METHODS: A total of
      119 healthy eyes with suspected glaucoma and glaucomatous eyes with 5 or more
      optic nerve stereophotographs, optical coherence tomography (OCT), and confocal
      scanning laser ophthalmoscopy (CSLO) all acquired within 6 months of each other
      were enrolled. Odds ratios to predict progression were determined by generalized
      estimating equation models. RESULTS: Median follow-up was 4.0 years (range: 1.5
      to 5.7 years). Fifteen eyes progressed by glaucoma progression analysis, 20 by
      visual field index, and 10 by both. Baseline parameters from stereophotographs
      (vertical cup-to-disc ratio and Disc Damage Likelihood Scale), OCT (global,
      superior quadrant, and inferior quadrant retinal nerve fiber layer thickness),
      and CSLO (cup shape measure and mean cup depth) were significant predictors of
      progression. Comparing the single best parameter from all models, only the OCT
      superior quadrant RNFL predicted progression. CONCLUSION: Baseline
      stereophotographs, OCT, and CSLO measurements may be clinically useful to predict
      glaucomatous visual field progression.

PMID- 22658311
TI  - Identification and characterization of chitin synthase genes in the postharvest
      citrus fruit pathogen Penicillium digitatum.
AB  - In this study, we carried out the isolation and characterization of chitin
      synthase genes (CHS) of the main citrus fruit postharvest pathogen Penicillium
      digitatum. Using distinct sets of degenerate primers designed from conserved
      regions of CHS genes of yeast and filamentous fungi, PCR methods, and a DNA
      genomic library, five putative CHS genes (PdigCHSI, PdigCHSII, PdigCHSIII,
      PdigCHSV, and PdigCHSVII) were identified, isolated, sequenced, and
      characterized. Phylogenetic analyses, sequence identity, and domain conservation
      support the annotation as CHS. A very high sequence identity and strong synteny
      were found with corresponding regions from the genome of Penicillium chrysogenum.
      Gene expression of P. digitatum CHS genes during mycelium axenic growth, under
      oxidative and osmotic stress conditions, and during infection of citrus fruits
      was confirmed and quantified using quantitative RT-PCR (qRT-PCR). PdigCHSIII had
      the highest expression among the five genes by one order of magnitude, while
      PdigCHSII had the lowest. However, PdigCHSII was strongly induced coincident with
      conidial production, suggesting a role in conidiogenesis. The expression of
      PdigCHSI, PdigCHSIII, PdigCHSV, and PdigCHSVII was upregulated during infection
      of citrus fruit. PdigCHSV and PdigCHSVII coexpressed in most of the experiments
      carried out, and they are separated by a 1.77 kb intergenic region and arranged
      in opposite directions.

PMID- 22658312
TI  - Photobiont selectivity and specificity in Caloplaca species in a fog-induced
      community in the Atacama Desert, northern Chile.
AB  - Little is known about the nature of the association between mycobionts and
      photobionts in isolated lichen communities. Here we studied the photobiont
      diversity of different Caloplaca species in a fog-induced community in the
      Atacama Desert. We compared nrDNA ITS sequences of both symbionts, photobionts
      and mycobionts, along with morphological characters of the different lichen
      thalli, to investigate the diversity and to assess the degree of selectivity and
      specificity of photobiont species in a community of Caloplaca species. Specimens
      of six fungal species (C. orthoclada, C. fernandeziana, and four undescribed
      species) were sampled along an altitudinal gradient on a coastal bluff with a
      strong fog presence, 60 km south of Iquique, Chile. The photobiont species in
      this community belong to three species of the genus Trebouxia in the strict
      sense: T. arboricola, T. decolorans, and T. gigantea. Most of the fungal species
      were lichenized with photobionts belonging to different haplotypes of T.
      arboricola and T. decolorans, although the algae of three specimens, associated
      with two fungal species (C. orthoclada and C. sp1), were related to
      representatives of T. gigantea. These results indicate that members of the genus
      Caloplaca in northern Chile have moderate photobiont selectivity and appear to be
      selective to members of the T. arboricola group. Also, at high altitudes, changes
      in the photobiontal haplotype composition were observed in comparison to lower
      altitudes, probably generated by a higher water availability given higher fog
      condensation and precipitation in the upper areas of the bluff. This may suggest
      that ecological factors, such as altitude and water availability could result in
      a local shift of the associated photobiont and specialization as a product of
      local adaptation.

PMID- 22658313
TI  - Evidence of natural hybridization among homothallic members of the basidiomycete
      Armillaria mellea sensu stricto.
AB  - Populations of Armillaria mellea (Basidiomycota, Agaricales) across much of its
      range are heterothallic; homothallic populations occur only in Africa (A. mellea
      ssp. africana), China (China Biological Species CBS G), and Japan (A. mellea ssp.
      nipponica). Monosporous isolates of heterothallic A. mellea are haploid and their
      mating behaviour is consistent with the requirement of two different alleles at
      two mating-type loci (tetrapolar mating system) to create a diploid individual.
      In contrast, monosporous isolates of homothallic A. mellea are putatively
      diploid; they bypass the haploid phase by undergoing karyogamy in the basidium (a
      unique type of secondary homothallism/pseudohomothallism). In order to determine
      the genetic origin of this homothallism, we analyzed genetic variation of 47
      heterothallic isolates from China, Europe, and North America, and 14 homothallic
      isolates from Africa, China, and Japan. Gene trees and mutational networks were
      constructed for partial mitochondrial gene ATP synthase subunit 6 (ATP6) and for
      the following nuclear genes: actin (ACTIN), elongation factor subunit 1-alpha
      (EFA), glyceraldehyde 3-phosphate dehydrogenase (GPD), and the RNA polymerase
      subunit II (RPB2). Homothallic isolates from Africa and Japan shared a common
      mitochondrial ATP6 haplotype with homothallic isolates from China, and are likely
      introductions. Homothallic isolates from China that shared a common mitochondrial
      haplotype with all European isolates did not share European nuclear haplotypes,
      as revealed by median-joining networks, but instead clustered with haplotypes
      from China or were intermediate between those of China and Europe. Such
      mitochondrial-nuclear discordance in homothallic isolates from China is
      indicative of hybridization between lineages originating from China and Europe.

PMID- 22658315
TI  - Determination of chrysene degradation under saline conditions by Fusarium sp.
      F092, a fungus screened from nature.
AB  - Sixty-two rotted wood and soil samples were used to screen for chrysene-degrading
      fungi. A strain of Fusarium, named F092, was identified as most capable of
      degrading chrysene. F092 was active under saline and nonsaline conditions,
      breaking down 48% of the chrysene in 30 d. The percentage of chrysene degraded
      did not change at 350/00 salinity with pH 8.2 in solid and liquid cultures. The
      degradation under saline conditions increased about 0.6- and 2.1-fold in cultures
      with polypeptone and Tween80, and 0.03-fold in agitated cultures. F092 secreted
      nonligninolytic enzymes named 1,2-dioxygenase and 2,3-dioxygenase. The level of
      1,2-dioxygenase activity reached 203.5 U L(-1) at 30 d and that of 2,3
      dioxygenase activity, 29.7 U L(-1) at 40 d. The degradation pathway was clarified
      from the intermediates produced; chrysene 1,2-oxide, chrysene trans-1,2
      dihydrodiol, 1-hydroxy 2-naphtoic acid, and catechol. F092 is a potential
      degrader of chrysene for bioremediation.

PMID- 22658316
TI  - Rapid strain classification and taxa delimitation within the edible mushroom
      genus Pleurotus through the use of diffuse reflectance infrared Fourier transform
      (DRIFT) spectroscopy.
AB  - Fourier transform infrared (FT-IR) spectroscopy has been successfully applied for
      the identification of bacteria and yeasts, but only to a limited extent for
      discriminating specific groups of filamentous fungi. In the frame of this study,
      73 strains - from different associated hosts/substrates and geographic regions -
      representing 16 taxa of the edible mushroom genus Pleurotus (Basidiomycota,
      Agaricales) were examined through the use of diffuse reflectance infrared Fourier
      transform (DRIFT) spectroscopy. A binary matrix, elaborated on the basis of
      presence/absence of specific absorbance peaks combined with cluster analysis,
      demonstrated that the spectral region 1800-600 cm(-1) permitted clear
      delimitation of individual strains into Pleurotus species. In addition, closely
      related species (e.g., Pleurotus ostreatus and Pleurotus pulmonarius) or taxa of
      the subgenus Coremiopleurotus demonstrated high similarity in their absorbance
      patterns, whereas genetically distinct entities such as Pleurotus dryinus,
      Pleurotus djamor, and Pleurotus eryngii provided spectra with noteworthy
      differences. When specific regions (1800-1700, 1360-1285, 1125-1068, and 950-650
      cm(-1)) were evaluated in respect to the absorbance values demonstrated by
      individual strains, it was evidenced that this methodology could be eventually
      exploited for the identification of unknown Pleurotus specimens with a stepwise
      process and with the aid of a dichotomous key developed for this purpose.
      Moreover, it was shown that the nature of original fungal material examined
      (mycelium, basidiomata, and basidiospores) had an effect on the outcome of such
      analyses, and so did the use of different mycelium growth substrates. In
      conclusion, application of FT-IR spectroscopy provided a fast, reliable, and cost
      efficient solution for the classification of pure cultures from closely related
      mushroom species.

PMID- 22658314
TI  - Molecular systematics in the genus Mucor with special regards to species
      encountered in cheese.
AB  - The genus Mucor, a member of the order Mucorales, comprises different species
      encountered in cheeses. Although fungi play a fundamental role in cheese
      manufacturing and ripening, the taxonomy of many fungal species found in cheese
      is poorly defined; indeed, this is the case for Mucor spp. In the present study,
      we assessed the phylogenetic relationships among 70 Mucor strains, including 36
      cheese isolates, by using a five gene phylogenetic approach combined with
      morphological analyses. Overall, at least six species of Mucor were identified
      among the cheese isolates including a possible new taxon. The present study also
      suggests that the genus Mucor comprises undescribed taxa and needs to be properly
      defined.

PMID- 22658317
TI  - Continuous and long-term monoxenic culture of the arbuscular mycorrhizal fungus
      Gigaspora decipiens in root organ culture.
AB  - Establishment of arbuscular mycorrhizal (AM) germplasm collections is complex
      because of the obligate biotrophic nature of AM fungi. Only a few AM species are
      routinely maintained in monoxenic culture with Ri T-DNA transformed roots as
      host. Incorporation of new AM species into this culture system is important for
      molecular, physiological, and taxonomical studies. Here we report for the first
      time the successful monoxenic culture of Gigaspora decipiens (JA2 strain) with
      transformed carrot (Daucus carota) roots. In vitro cultures were established from
      field-collected spores; sub-culture of newly in vitro formed spores was
      established over five successive generations for a period of 6 y. Although
      initial culture of field-collected spores was difficult successive sub-cultures
      appeared to be adapted to the in vitro growing conditions. The JA2 strain of G.
      decipiens completed its life cycle while maintaining its morphological
      characteristics, stability, and propagule viability under the monoxenic
      conditions over several generations. This stable and homogeneous monoxenic
      material obtained for G. decipiens is part of the Banco de Glomeromycota In Vitro
      (BGIV, http://www.bgiv.com.ar), and could facilitate morphological,
      physiological, and molecular analysis of this AM species.

PMID- 22658318
TI  - If there is no overall survival benefit in metastatic breast cancer: does it
      imply lack of efficacy? Taxanes as an example.
AB  - In recent years, new drugs have shown activity in metastatic breast cancer, but
      not always resulting in an overall survival benefit. This has led to discussions
      if such drugs, mainly expensive drugs, should be reimbursed especially when also
      not leading to improvement in quality of life. For that reason, we decided to
      systematically review taxane-based chemotherapy studies in early and metastatic
      breast cancer, to assess which factors may have caused the differential outcome.
      Taxanes did not improve survival in metastatic breast cancer trials, whereas they
      did so in early breast cancer trials. We questioned if the differential outcome
      of taxanes in metastatic breast cancer might be caused by the chosen comparator
      and study design. We noticed that in the majority of metastatic breast cancer
      studies taxanes were used as a substitute for other active cytotoxic drugs,
      mainly cyclophosphamide, whereas in early breast cancer studies taxanes were
      generally delivered in addition to a standard regimen. We conclude from our
      analyses that use of taxanes instead of other active drugs explains the lack of
      overall survival benefit in metastatic breast cancer trials. Further, our results
      suggest that cyclophosphamide is an important drug in the treatment of breast
      cancer, being as effective as optimally dosed taxanes and anthracyclines. By
      studying the different study designs and comparators in both settings, we were
      able to demonstrate their impact on efficacy endpoints. We conclude, therefore,
      that re-assessment of studies of drugs both assessed in metastatic and early
      breast cancer provides a new tool for improved understanding.

PMID- 22658319
TI  - Current approaches and future directions in the treatment of HER2-positive breast
      cancer.
AB  - Human epidermal growth factor receptor 2 (HER2), a member of the ErbB family of
      transmembrane receptor tyrosine kinases, is amplified in 20-30% of invasive
      breast cancers. HER2 amplification is associated with metastasis and reduced
      survival. Two HER2-directed therapies have been approved by the United States
      Food and Drug Administration for the treatment of HER2-overexpressing breast
      cancer: trastuzumab, a humanized monoclonal antibody against the extracellular
      portion of HER2; and lapatinib, a dual HER2- and epidermal growth factor receptor
      specific tyrosine kinase inhibitor. Despite the improvement in overall survival
      with the addition of HER2-targeted agents to chemotherapy, many patients do not
      benefit from these agents because of inherent resistance. In addition, many
      patients who achieve an initial response eventually acquire drug resistance.
      Currently, several mechanisms of resistance have been described, including
      mutations in other signaling pathways, expression of a truncated form of HER2,
      receptor crosstalk, and autophagy. There are several approaches under study to
      target these pathways of resistance, including blocking PI3 kinase and mammalian
      target of rapamycin signaling, blocking neoangiogenesis and the vascular
      endothelial growth factor axis, using monoclonal antibody targeting of the HER2
      dimerization site, and using HER2 monoclonal antibody-drug conjugates. Here we
      will review the current scientific rationale for these agents and how
      combinations of these agents may yield additive or synergistic effects and lead
      to improved outcomes for patients with HER2-amplified breast cancer.

PMID- 22658321
TI  - The effect of renin-angiotensin-aldosterone system blockade on contrast-induced
      acute kidney injury: a propensity-matched study.
AB  - BACKGROUND: The role of the angiotensin-converting enzyme (ACE) inhibitor and
      angiotensin receptor blocker (ARB) in the pathophysiology of contrast-induced
      acute kidney injury (AKI) is controversial, and the available literature is
      contradictory. STUDY DESIGN: A retrospective propensity score-matched study to
      analyze the effect of ACE-inhibitor/ARB therapy on the development of contrast
      induced AKI. SETTING & PARTICIPANTS: Using propensity score matching, 1,322 ACE
      inhibitor/ARB recipients and nonrecipients were paired for analysis from 5,299
      patients and fulfilled the inclusion criteria among 11,447 patients receiving
      coronary angiography (CAG) or percutaneous coronary intervention. PREDICTORS: ACE
      inhibitor/ARB use based on prescription and risk factors for contrast-induced
      AKI. OUTCOMES: The incidence of contrast-induced AKI defined by AKI Network
      (AKIN) criteria: an absolute increase in serum creatinine levels >=0.3 mg/dL or a
      relative increase >=50% from baseline values within 48 hours after exposure to
      the contrast medium. MEASUREMENTS: Baseline serum creatinine, hemoglobin, and
      albumin levels; volume of contrast agents; preprocedural medication; and post-CAG
      serum creatinine levels. RESULTS: An ACE inhibitor/ARB was prescribed for 64.0%
      of patients receiving CAG. ACE-inhibitor/ARB users showed an increased incidence
      of contrast-induced AKI after propensity score matching (11.4% vs 6.3%; P <
      0.001). In multivariable analysis, use of ACE inhibitors/ARBs remained an
      independent and significant predictor of contrast-induced AKI in an unmatched
      cohort (OR, 1.39; 95% CI, 1.10-1.76; P = 0.06). In the matched cohort, use of ACE
      inhibitors/ARBs also was associated with a higher adjusted OR of contrast-induced
      AKI (OR, 1.43; 95% CI, 1.06-1.94; P = 0.02). LIMITATIONS: A retrospective study
      at a single center. CONCLUSIONS: Use of ACE inhibitors/ARBs during CAG has a
      possible influence to increase the incidence of contrast-induced AKI. Further
      randomized clinical trials are warranted to confirm the effect of ACE
      inhibitor/ARB therapy on the development of contrast-induced AKI.

PMID- 22658320
TI  - Modulating therapeutic effects of the c-Src inhibitor via oestrogen receptor and
      human epidermal growth factor receptor 2 in breast cancer cell lines.
AB  - PURPOSE: c-Src is an important adapter protein with oestrogen receptor (ER) and
      human epidermal growth factor receptor 2 (HER2), which validates it as an
      attractive target for the treatment of breast cancer. A specific c-Src inhibitor,
      4-amino-5-(4-chlorophenyl)-7(t-butyl)pyrazolo[3,4-d]pyrinidine (PP2), was
      utilised to block c-Src activity to identify targeted vulnerabilities affected by
      ER and HER2 in a panel of breast cancer cell lines. METHODS: ER, growth factor
      receptors and signalling pathways were detected by Western-blot. The DNA content
      of the cells was determined by using a DNA fluorescence quantitation kit. Cell
      cycles were analysed by flow cytometry. RESULTS: The antiproliferative effect of
      PP2 closely correlated with the inhibition of c-Src mediated extracellular signal
      regulated kinase/mitogen-activated protein kinase (ERK/MAPK) and/or
      phosphoinositide 3-kinase (PI3K)/Akt growth pathways. Inhibition of c-Src
      tyrosine kinase predominantly blocked ER negative breast cancer cell growth,
      particularly the triple (i.e. ER, progesterone receptor (PR), and HER2) negative
      cells. In contrast, ER negative Sk-Br-3 cells with highest HER2 phosphorylation
      were resistant to PP2, in which hyper-activated HER2 directly regulated growth
      pathways. However, blocking c-Src recovered ER expression and down-regulated HER2
      which made Sk-Br-3 cells regain responsiveness to 4-hydroxytamoxifen. The
      majority of ER positive cells were not sensitive to PP2 regardless of wild-type
      or endocrine resistant cell lines. CONCLUSIONS: c-Src mediates the essential role
      of growth pathways in ER negative breast cancer cells. The ER positive and HER2
      over-activation are two important predictive biomarkers for the resistance to a c
      Src inhibitor. These data provided an important therapeutic rationale for patient
      selection in clinical trials with c-Src inhibitors in breast cancer.

PMID- 22658322
TI  - A systematic review of benzoyl peroxide for acne vulgaris.
AB  - OBJECTIVE: Comparative trials of benzoyl peroxide (BPO) have yielded
      contradictory results on its effectiveness for acne vulgaris. The aim of the
      study was to synthesise the evidence for the effectiveness of BPO-containing
      topical products for facial acne vulgaris. DESIGN: Systematic review. METHODS:
      The Cochrane Central Register of Controlled trials, Cochrane Library, MEDLINE and
      other relevant databases were searched without publication date or language
      restriction. RESULTS: We identified 22 trials involving 2212 participants; 12
      trials compared BPO as single agent while the other 10 trials compared BPO in
      combination products. All trials reported lesion count as the outcome measure but
      only five trials provided numerical data. However, pooling of data from these
      trials was inappropriate due to variations between trials in terms of acne
      severity, comparator used and trial duration. Overall the study quality was fair
      but most studies had some bias particularly in method of random generation and
      allocation concealment. Although the results provide some evidence that BPO
      reduces acne-lesion count, the available evidence is not robust enough for firm
      conclusions. CONCLUSIONS: There is no high quality evidence that topical BPO
      improves facial acne vulgaris, and further research is needed.

PMID- 22658323
TI  - EIF4G1 in familial Parkinson's disease: pathogenic mutations or rare benign
      variants?
AB  - Mutations in the eukaryotic translation initiation factor 4-gamma (EIF4G1) gene,
      encoding a component of the eIF4F translation initiation complex, were recently
      reported as a possible cause for the autosomal dominant form of Parkinson's
      disease (PD). Here, we describe the screening of all 31 EIF4G1 coding exons in a
      series of 251 index cases with autosomal dominant PD, mostly of French origin and
      in 236 European control subjects. We identified 12 rare coding variants (either
      nonsynonymous amino acid substitutions or in frame deletions/insertions),
      including 6 variants present only in cases and 3 in controls. Segregation was
      possible only for 1 variant (p.E462delInsGK) that was found in 2 affected
      siblings. In addition, we found 2 previously reported pathogenic variants in 2
      isolated patients (p.G686C) and in a control subject (p.R1197W). These data do
      not support the pathogenicity of several EIF4G1 variants in PD, at least in the
      French population.

PMID- 22658324
TI  - Asymmetric learning to avoid heterospecific males in Mesocricetus hamsters.
AB  - If a female mates with a male of a closely related species, her fitness is likely
      to decline. Consequently, females may develop behavioral mechanisms to avoid
      mating with heterospecific males. In some species, one such mechanism is for
      adult females to learn to discriminate against heterospecific males after
      exposure to such males. We have previously shown that adult, female Syrian
      hamsters (Mesocricetus auratus) learn to discriminate against male Turkish
      hamsters (Mesocricetus brandti) after exposure to a single heterospecific male
      during 8 days across a wire-mesh barrier. Here we repeated that experiment but
      this time we exposed female Turkish hamsters to a male Syrian hamster for 8 days
      and then measured sexual and aggressive behaviors towards that heterospecific
      male and towards a conspecific male. In contrast to female Syrian hamsters,
      female Turkish hamsters did not differ in their latency to go into lordosis or in
      any measure of aggression towards either type of male. Female Turkish hamsters
      spent less time in lordosis with the heterospecific male, but the percentage of
      trials in which females copulated with conspecific and heterospecific males did
      not differ. When comparing females from both species that had been exposed to a
      heterospecific male for 8days, female Syrian hamsters copulated less and were
      more aggressive towards the heterospecific male compared to the behavior of
      female Turkish hamsters. We discuss how this asymmetric response between females
      of the two species may be due to the much larger geographical range of Turkish
      hamsters compared to Syrian hamsters.

PMID- 22658326
TI  - Cabergoline associated with first episode mania.

PMID- 22658327
TI  - A case of Shoshin Beriberi: lessons old and new for the psychiatrist.

PMID- 22658325
TI  - Pediatric psychosomatic medicine: creating a template for training.
AB  - There is a critical public health problem in the United States today, the problem
      of childhood psychiatric disorders in youngsters with physical illnesses.
      Currently there is a pressing need for well-trained pediatric psychosomatic
      medicine practitioners as well as advanced training in the field. Yet, this
      training does not currently exist. This article will present the innovative
      Montefiore Medical Center/Albert Einstein College of Medicine (MMC/AECOM) program
      as a model for a training curriculum, clinical training experience, and clinical
      research training setting in this important and rapidly expanding area of need in
      pediatric mental health.

PMID- 22658328
TI  - Lithium-induced nephrogenic diabetes insipidus after gastric banding.

PMID- 22658330
TI  - Bladder diverticula in children.
AB  - This review of bladder diverticula in children includes: historical aspects of
      the condition, its presentation and diagnosis, as well as management options. The
      purpose of the review is to provide a comprehensive and in-depth understanding of
      a relatively infrequent but clinically challenging urologic abnormality that may
      affect not only the bladder but also the upper urinary tract and kidney.

PMID- 22658329
TI  - Personality disorders in hypochondriasis: prevalence and comparison with two
      anxiety disorders.
AB  - OBJECTIVE: Symptoms of hypochondriasis are sometimes attributed to personality
      psychopathology by health care providers. The goals of this study were to assess
      the prevalence of personality disorder (PD) comorbidity in hypochondriasis (HYP)
      and to compare the PD comorbidity profile of patients with HYP with that found
      among patients with other disorders characterized by intrusive thoughts and
      fears. METHODS: Structured Clinical Interview for DSM-IV Axis I and Axis II
      Disorders (SCID-I and SCID-II) were administered to 179 individuals: 62 with HYP,
      46 with obsessive-compulsive disorder (OCD), and 71 with social anxiety disorder
      (SAD). For group contrasts, the samples were "purified" of the comparison
      comorbid disorders. General linear models were used to test the combined effect
      of group (HYP, OCD, SAD), age, and gender on the PD outcome variables. RESULTS:
      59.7% of HYP subjects had no Axis II comorbidity. The most common PDs in HYP were
      paranoid (19.4%), avoidant (17.7%), and obsessive-compulsive (14.5%). HYP
      significantly differed from SAD in the likelihood of a cluster C disorder,
      whereas no significant difference was noted for HYP vs. OCD. The proportion of
      subjects having at least two PDs was not significantly different for HYP vs. OCD
      or for HYP vs. SAD. CONCLUSION: Although 40% of patients with hypochondriasis
      have PD comorbidity as assessed by the SCID-II, the amount of PD comorbidity is
      not significantly different than found among individuals with two comparison
      anxiety disorders. Therefore, health providers should be aware that PD may
      complicate the clinical profile of HYP, but they should avoid assuming that PD
      psychopathology is the primary source of hypochondriacal distress.

PMID- 22658331
TI  - Did a discrete event 200,000-100,000 years ago produce modern humans?
AB  - Scenarios for modern human origins are often predicated on the assumption that
      modern humans arose 200,000-100,000 years ago in Africa. This assumption implies
      that something 'special' happened at this point in time in Africa, such as the
      speciation that produced Homo sapiens, a severe bottleneck in human population
      size, or a combination of the two. The common thread is that after the divergence
      of the modern human and Neandertal evolutionary lineages ~400,000 years ago,
      there was another discrete event near in time to the Middle-Late Pleistocene
      boundary that produced modern humans. Alternatively, modern human origins could
      have been a lengthy process that lasted from the divergence of the modern human
      and Neandertal evolutionary lineages to the expansion of modern humans out of
      Africa, and nothing out of the ordinary happened 200,000-100,000 years ago in
      Africa. Three pieces of biological (fossil morphology and DNA sequences) evidence
      are typically cited in support of discrete event models. First, living human
      mitochondrial DNA haplotypes coalesce ~200,000 years ago. Second, fossil
      specimens that are usually classified as 'anatomically modern' seem to appear
      shortly afterward in the African fossil record. Third, it is argued that these
      anatomically modern fossils are morphologically quite different from the fossils
      that preceded them. Here I use theory from population and quantitative genetics
      to show that lengthy process models are also consistent with current biological
      evidence. That this class of models is a viable option has implications for how
      modern human origins is conceptualized.

PMID- 22658332
TI  - Differences between Neandertal and modern human infant and child growth models.
AB  - Studying the emergence of distinctive human growth patterns is essential to
      understanding the evolution of our species. The large number of Neandertal
      fossils makes this species the best candidate for a comparative study of growth
      patterns in archaic and modern humans. Here, Neandertal height growth during
      infancy and early childhood is described using a mathematical model. Height
      growth velocities for individuals five years old or younger are modelled as age
      functions based on different estimates of height and age for a set of ten
      Neandertal infants and children. The estimated heights of each Neandertal
      individual are compared with those of two modern human populations based on
      longitudinal and cross-sectional data. The model highlights differences in growth
      velocity during infancy (from the age of five months onward). We find that
      statural growth in Neandertal infants is much slower than that seen in modern
      humans, Neandertal growth is similar to modern humans at birth, but decreases
      around the third or fourth month. The markedly slower growth rates of Neandertal
      infants may be attributable to ontogenetic constraints or to metabolic stress,
      and contribute to short achieved adult stature relative to modern humans.

PMID- 22658333
TI  - Multi-proxy approach detects heterogeneous habitats for primates during the
      Miocene climatic optimum in Central Europe.
AB  - The present study attempts to characterize the environmental conditions that
      prevailed along the western shores of the Central Paratethys and its hinterland
      during the early middle Miocene at the same time t primates reached their peak in
      species diversity in Central Europe. Based on faunal structure (using cenograms),
      paleotemperature reconstruction (using cricetid diversity), and dietary
      reconstruction of ruminants (using molar micro-wear analyses), four faunal
      assemblages are used to characterize the regional environmental context. The
      cenograms for Goriach and Devinska Nova Ves Zapfe's fissure site support the
      presence of mosaic environments with open areas under rather humid conditions.
      This is also supported by the dental micro-wear analyses of ruminants. The
      species of Palaeomerycidae were most probably the only predominant browsers.
      Surprisingly, the three cervids, Dicrocerus, Heteroprox, and Euprox, were highly
      involved in grazing. Pseudoeotragus seegrabensis was likely a generalist and the
      two specimens assigned to the second bovid, Eotragus clavatus, were browsers. The
      two species of tragulids plot between fruit browsers and generalists. Moreover,
      paleotemperatures based on cricetid diversity estimate mean annual temperature at
      about 18  degrees C with potential high seasonal variations. These data support
      the predominance of mosaic landscapes along the western shores of the Central
      Paratethys and its hinterland during the Miocene Climatic Optimum as primates
      reach a peak in species diversity. This result lends credence to the hypothesis
      that environmental heterogeneity favours radiation among mammals, and that the
      specific environmental context of the Central Paratethys western border might
      explain the high diversity of the middle Miocene primates.

PMID- 22658334
TI  - Plio-Pleistocene synsedimentary fault compartments, foundation for the eastern
      Olduvai Basin paleoenvironmental mosaic, Tanzania.
AB  - Normal faults displacing Upper Bed I and Lower Bed II strata of the Plio
      Pleistocene Lake Olduvai were studied on the basis of facies and thickness
      changes as well as diversion of transport directions across them in order to
      establish criteria for their synsedimentary activity. Decompacted differential
      thicknesses across faults were then used to calculate average fault slip rates of
      0.05-0.47 mm/yr for the Tuff IE/IF interval (Upper Bed I) and 0.01-0.13 mm/yr for
      the Tuff IF/IIA section (Lower Bed II). Considering fault recurrence intervals of
      ~1000 years, fault scarp heights potentially achieved average values of 0.05-0.47
      m and a maximum value of 5.4 m during Upper Bed I, which dropped to average
      values of 0.01-0.13 m and a localized maximum of 0.72 m during Lower Bed II
      deposition. Synsedimentary faults were of importance to the form and paleoecology
      of landscapes utilized by early hominins, most traceably and provably Homo
      habilis as illustrated by the recurrent density and compositional pattern of
      Oldowan stone artifact assemblage variation across them. Two potential
      relationship factors are: (1) fault scarp topographies controlled sediment
      distribution, surface, and subsurface hydrology, and thus vegetation, so that a
      resulting mosaic of microenvironments and paleoecologies provided a variety of
      opportunities for omnivorous hominins; and (2) they ensured that the most
      voluminous and violent pyroclastic flows from the Mt. Olmoti volcano were dammed
      and conduited away from the Olduvai Basin depocenter, when otherwise a single or
      set of ignimbrite flows might have filled and devastated the topography that
      contained the central lake body. In addition, hydraulically active faults may
      have conduited groundwater, supporting freshwater springs and wetlands and
      favoring growth of trees.

PMID- 22658335
TI  - Social organization and the evolution of cumulative technology in apes and
      hominins.
AB  - Culturally supported accumulation (or ratcheting) of technological complexity is
      widely seen as characterizing hominin technology relative to that of the extant
      great apes, and thus as representing a threshold in cultural evolution. To
      explain this divide, we modeled the process of cultural accumulation of
      technology, which we defined as adding new actions to existing ones to create new
      functional combinations, based on a model for great ape tool use. The model shows
      that intraspecific and interspecific variation in the presence of simple and
      cumulative technology among extant orangutans and chimpanzees is largely due to
      variation in sociability, and hence opportunities for social learning. The model
      also suggests that the adoption of extensive allomaternal care (cooperative
      breeding) in early Pleistocene Homo, which led to an increase in sociability and
      to teaching, and hence increased efficiency of social learning, was enough to
      facilitate technological ratcheting. Hence, socioecological changes, rather than
      advances in cognitive abilities, can account for the cumulative cultural changes
      seen until the origin of the Acheulean. The consequent increase in the reliance
      on technology could have served as the pacemaker for increased cognitive
      abilities. Our results also suggest that a more important watershed in cultural
      evolution was the rise of donated culture (technology or concepts), in which
      technology or concepts was transferred to naive individuals, allowing them to
      skip many learning steps, and specialization arose, which allowed individuals to
      learn only a subset of the population's skills.

PMID- 22658336
TI  - Regioselective N1-alkylation of 3,4-dihydropyrimidine-2(1H)-ones: screening of
      their biological activities against Ca(2+)-ATPase.
AB  - A regioselective N1-alkylation of 3,4-dihydropyrimidin-2(1H)-ones using a very
      efficient mild base Cs(2)CO(3) and alkyl halides at room temperature has been
      reported. The selectivity of this methodology is excellent and the yields of the
      alkylated products are very good. Furthermore inhibitory action of both the 3,4
      dihydropyrimidin-2(1H)-ones and the N1-alkylated derivatives were tested on
      Ca(2+)-ATPase, which revealed that the parent compounds can act as Ca(2+)-ATPase
      inhibitors whereas the N1-alkylated derivatives are inefficient for this purpose.

PMID- 22658337
TI  - Statin use and the risk of incident diabetes mellitus: a review of the
      literature.
AB  - Statins are one of the most widely prescribed medications in the world. They are
      beneficial in both the primary and secondary prevention of atherosclerotic
      cardiovascular disease events. In recent years, however, concern has been raised
      regarding an increased incidence of new-onset diabetes mellitus observed in
      clinical trials of statin therapy. While most randomized, placebo controlled,
      statin trials have not included the incidence of new-onset diabetes as a major
      primary end point, a very small but consistent adverse effect on glycosylated
      hemoglobin and blood glucose levels, which is presently of unknown clinical
      significance, has been observed. Importantly, it should be remembered that some
      patient subgroups exposed to statin therapy, such as those with the metabolic
      syndrome, may already be particularly vulnerable to developing diabetes mellitus.
      Experimentally, although the weight of evidence suggests a protective effect of
      statins on the development of diabetes mellitus, basic science studies have
      documented conflicting evidence regarding both the beneficial and adverse effects
      from statin therapy on insulin secretion and sensitivity. In addition, the
      possibility that statin-induced muscle inflammation may elevate blood glucose
      levels cannot be excluded. Thus, although the biological plausibility of statins
      inducing diabetes certainly may exist, at the present time, sufficient high
      quality scientific evidence does not exist to definitively establish the veracity
      or the strength of any putative cause and effect relationship. And without such
      evidence, there is no current impetus to alter existing clinical practice
      recommendations regarding the appropriate use of statin therapy.

PMID- 22658338
TI  - Preparation of proton rich radionuclides in support of radiochemical analysis.
AB  - The production of proton rich radionuclides supports a wide range of
      radiochemical analyses via radioactive yield tracers ((95m)Tc and (236)Pu). In
      recent years, NPL and the University of Birmingham cyclotron have collaborated to
      produce these, and other, radionuclides.

PMID- 22658339
TI  - Chronic clomipramine treatment restores hippocampal expression of glial cell line
      derived neurotrophic factor in a rat model of depression.
AB  - BACKGROUND: Because there is evidence that certain neurotrophic factors are
      involved in depression and the mechanism of antidepressant treatment, it is
      hypothesized that neurotrophic factors may also play a functional role in the
      etiology of depression and treatment. Glial cell line-derived neurotrophic factor
      (GDNF) is a member of the transforming growth factor (TGF-beta)-super-family. We
      performed a study to assess the impact of chronic unpredictable stress (CUS) and
      clomipramine treatment on GDNF expression in the rat hippocampus. METHOD: Using a
      rat model of CUS-induced depression, we administered clomipramine, one of the
      typical antidepressants, every day for 3 weeks starting 2 weeks after the
      beginning of the experiment. GDNF level in the hippocampus was detected by
      immunohistochemsitry, Western blot analysis, and reverse transcription-polymerase
      chain reaction (RT-PCR). Behavioral changes were measured by forced swimming test
      (FST) and open field test (OFT). RESULTS: Animals exposed to CUS showed
      depression-like behavior and exhibited a significant decrease in GDNF expression
      in the hippocampus. Chronic clomipramine treatment reversed the behavioral
      deficits and the decrease in GDNF levels induced by CUS. LIMITATION: The
      relatively small number of the depression-model rats may cause some bias of
      behavioral tests. CONCLUSION: In our study, chronic clomipramine treatment
      restored GDNF expression in the hippocampus of CUS-induced depression rats,
      suggesting that GDNF is involved in the behavioral responses to antidepressants.
      The beneficial effects of clomipramine suggest that GDNF may be a viable target
      for new antidepressant drug development.

PMID- 22658340
TI  - Psychometric assessment of the Correa-Barrick Postpartum Depression Scale.
AB  - INTRODUCTION: Empirical evidence has suggested an association between mood and
      color sensitivity. The purpose of this study is to report on the psychometric
      properties of a new postpartum depression rating scale while at the same time
      showing a correlation between depression severity and impaired color sensitivity.
      METHODS: Using a survey design of a sample of 17 postpartum patients, color
      sensitivity was assessed by the patient's response to a self-report depression
      scale item, "I notice that everything seems gray/cloudy/drab/lacking color".
      RESULTS: There was a statistically significant finding between color sensitivity
      and depression, r=.50, P<.05. Based on classical test theory, findings also
      supported the validity and reliability of the new scale. LIMITATIONS: The
      limitation of the study was the small sample size, but it also suggests that the
      findings seem particularly robust in view of this. CONCLUSIONS: This scale could
      be used in clinical practice to detect early signs of depression for prompt
      intervention. Referral should be made to mental health providers for follow-up to
      insure that the mother is not psychotic or so depressed that she cannot care for
      the baby. Color sensitivity impairment and depression severity has been
      replicated several times with different samples. It is worthwhile pursuing the
      pathophysiological basis for this.

PMID- 22658341
TI  - Infection of the right iliac fossa.
AB  - Febrile pain in the right iliac fossa is one of the most common reasons for
      consulting at an emergency service. Within this framework, the main diagnosis
      that is considered is appendicitis, the main complication of which is
      perforation. However, a certain number of other conditions can be responsible for
      this clinical picture, primarily including digestive tract and mesentery
      disorders including mesenteric lymphadenitis, Crohn's disease, infectious
      enterocolitis, small intestine or colonic diverticulitis, ischaemic colitis or
      cancer of the caecum. This article illustrates the imaging semiology of the
      various right colonic, iliac, mesenteric and appendicular conditions that could
      potentially cause an infection of the right iliac fossa. It specifies the
      indications of ultrasound and CT scans, respectively, which depend on the age of
      the patient and the clinical signs and symptoms. Though the CT scan is commonly
      used in abdominal emergencies in general, and particularly in clinical pictures
      of infection of the right iliac fossa, ultrasound remains recommended as first
      line imaging when confronted with suspected appendicitis or lymphadenitis in a
      young subject or in the monitoring of Crohn's disease.

PMID- 22658342
TI  - The effect of posterior tooth loss on the expression of type II collagen, IL
      1beta and VEGF in the condylar cartilage of growing rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of unilateral and
      bilateral loss of posterior occlusal support on the expression of type II
      collagen, interleukin-1beta and VEGF in the condylar cartilage of growing rats.
      DESIGN: Thirty female Wistar rats (5 weeks old) were randomized into three
      groups: control, unilateral extraction of mandibular molar teeth, bilateral
      extraction of mandibular molar teeth. Animals were sacrificed 8 weeks after tooth
      extraction and the temporomandibular joints were prepared for immunohistochemical
      analysis. RESULTS: Bilateral molar extraction increased the expression of
      interleukin-1beta (P<0.01) and VEGF (P<0.01), while unilateral extraction
      increased the expression of interleukin-1beta (P<0.05) and type II collagen
      (P<0.01). The expression of VEGF was higher on the extracted than on the non
      extracted side (P<0.01) after unilateral extraction. CONCLUSION: Loss of
      posterior occlusal support alters the expression of type II collagen, interleukin
      1beta and VEGF in the condylar cartilage of rats. The expression pattern of these
      proteins is different when loss of occlusal support was bilateral or unilateral,
      including differences between extracted and non-extracted sides.

PMID- 22658343
TI  - Prevalence of nephropathies in children and adolescents and alterations in renal
      biopsies in Minas Gerais, Brazil, from 1996 to 2010.
AB  - Renal biopsy is an important method of diagnosis and prognosis in children and
      adolescents with renal diseases, and there are few studies describing the
      histopathologic alterations in renal biopsies in these age groups. The aim of
      this study was to evaluate the incidence of morphologic alterations described in
      renal biopsies carried out in children and adolescents. Patients aged between 1
      month and 18 years were observed from 1996 to 2010 and were separated into 3 age
      groups: 0 to 6 (group 1, n = 29), 6 to 12 (group 2, n = 31), and 13 to 18 (group
      3, n = 77) years. Morphologic alterations were evaluated according to light
      microscopy, immunofluorescence, and electron microscopy findings. The most common
      glomerulopathies observed in these different age groups were as follows: group 1
      podocytopathy (34.78%), hereditary proteinurias 5 (21.73%), lupus nephritis
      (13.04%), and Berger disease (8.69%); group 2-podocytopathy (44.44%), acute
      diffuse glomerulonephritis (22.22%), Berger disease (11.11%), and Alport syndrome
      or thin membrane disease (11.11%); and group 3-lupus nephritis (22.85%),
      podocytopathy (20.00%), Berger disease (15.71%), and membranous glomerulopathies
      (11.42%). This study allows for better knowledge of the prevalence of
      nephropathies in children and adolescents and shows that a well-supported early
      diagnosis is indispensable for a more adequate treatment of patients with renal
      diseases.

PMID- 22658344
TI  - Role of hormone receptor expression in patients with advanced-stage lung cancer
      treated with chemotherapy.
AB  - BACKGROUND: Evidence that supports a role for hormonal status in lung cancer has
      been inconsistently reported and is still unclear. We retrospectively assessed
      the potential correlation between sex-linked hormone receptor expression and the
      clinical outcome of patients with advanced-stage lung cancer treated with
      chemotherapy. PATIENTS AND METHODS: Based on tissue availability, 130 consecutive
      patients diagnosed at San Luigi Hospital from January 2008 to June 2010 were
      collected, including 24 small-cell lung cancer, 57 adenocarcinomas, 34 squamous
      cell carcinomas, 5 large-cell carcinomas, and 10 non-small-cell lung cancer-not
      otherwise specified. The immunohistochemical expression of estrogen receptors (ER
      alpha and ER-beta) and progesterone receptor, aromatase, epidermal growth factor
      receptor (EGFR), and excision repair cross-complementing 1 (ERCC1) was assessed.
      RESULTS: ER-beta nuclear expression was higher than ER-alpha and progesterone
      receptor, whose expression was null or weak (mainly in women). ER-beta expression
      was significantly higher in patients with metastatic disease compared with all
      other disease stages (P = .02). EGFR expression was strongly correlated with non
      small-cell lung cancer histology, being higher in squamous types and stage
      related. In men, aromatase positive cases had a worse outcome (P = .03) as well
      as in men with non-small-cell lung cancer and high ER-beta expression. In the
      latter group, the combined aromatase negative and/or low ER-beta expression and
      low ERCC1 and/or low ER-beta expression showed a better outcome (P = .026; P =
      .03, respectively). CONCLUSION: In patients with advanced-stage lung cancer
      treated with chemotherapy, the prognostic and predictive role of sex-linked
      hormone receptor expression, if any, is of borderline significance and is
      restricted to selected subgroups of patients.

PMID- 22658345
TI  - Inflammation: a link between endometriosis and preterm birth.
AB  - Endometriosis is a chronic inflammatory disease affecting women's health. Pain
      and infertility are the major symptoms caused by a hormonal/immunological
      dysfunction, which causes an endometrial impairment. The same pathogenetic
      mechanisms are also associated with preterm birth: hormones, cytokines,
      neurohormones, and growth factors interact in modulating extracellular matrix and
      prostaglandin secretion, thus activating the inflammatory process in placental
      membranes and myometrium. An overlap of molecules and mechanisms may explain the
      evidence that preterm birth is a common outcome in pregnant patients with
      endometriosis.

PMID- 22658346
TI  - Somatic stem cells and tissue engineering shed light on unsolved clinical issues
      in reproductive medicine: in stem cells we trust.
AB  - Three experts in regenerative medicine explore the evidence and expanding future
      clinical applicability of the human ovarian and endometrial stem cell population,
      and tissue engineering of reproductive organs and tissues.

PMID- 22658347
TI  - In vitro maturation or in vitro fertilization for women with polycystic ovaries?
      A case-control study of 194 treatment cycles.
AB  - OBJECTIVE: To compare the outcome of unstimulated in vitro maturation (IVM) and
      routine IVF/intracytoplasmic sperm injection (ICSI) for women with polycystic
      ovaries (PCO). DESIGN: Retrospective case-control study. SETTING: Fertility unit.
      PATIENT(S): Ninety-seven patients undergoing IVM were compared with 97 patients
      undergoing IVF. All had PCO and matched for age, infertility diagnosis, and
      ovulatory status. INTERVENTION(S): In vitro maturation cycles were unstimulated
      and hCG was administered 35-40 hours before oocyte retrieval. Oocytes were
      matured in vitro for 24-48 hours before insemination by ICSI. Endometrial priming
      with E(2) and P was commenced from the day of egg retrieval and one to two
      embryos were transferred on days 2-5 of development. Standard long protocol
      IVF/ICSI was used in the control group. MAIN OUTCOME MEASURE(S): Live birth rate
      per cycle and ovarian hyperstimulation syndrome (OHSS) rate. RESULT(S): Overall,
      65% of IVM eggs matured in vitro in the IVM group. Implantation rates were
      significantly higher in the IVF group (19.4% vs. 12.9%) as clinical pregnancy
      rates (50.5% vs. 19.6%) and live birth rates (44.3% vs. 16.5%) than in the IVM
      group. The OHSS rate was significantly higher in the IVF group (8.2% vs. 0%).
      CONCLUSION(S): In vitro maturation is a safer and simpler alternative to
      conventional IVF for women with PCO. It avoids difficulties of gonadotropin
      stimulation and the risk of OHSS but has a significantly lower live birth rate.
      Current research projects aim to close the success gap between IVM and IVF.

PMID- 22658348
TI  - Swimming in obstructive sleep apnea patient could be a risk factor of aortic
      dissection?

PMID- 22658349
TI  - Individual risk prediction model for incident cardiovascular disease: a Bayesian
      clinical reasoning approach.
AB  - BACKGROUND: A Bayesian clinical reasoning model was developed to predict an
      individual risk for cardiovascular disease (CVD) for desk-top reference. METHODS:
      Three Bayesian models were constructed to estimate the CVD risk by sequentially
      incorporating demographic features (basic), six metabolic syndrome components
      (metabolic score) and conventional risk factors (enhanced model). By considering
      clinical weights (regression coefficients) of each model as normal distribution,
      individual risk can be predicted making allowance for uncertainty of clinical
      weights. A community-based cohort that enrolled 64,489 participants free of CVD
      at baseline and followed up over five years to ascertain newly diagnosed CVD
      cases during the period through 2000 to 2004 was used for the illustration of the
      three proposed models (full empirical data are available from website
      http://homepage.ntu.edu.tw/~chenlin/CVD_prediction_data.rar). RESULTS: The
      proposed models can be applied to predicting the CVD risk with any combination of
      risk factors. For a 47-year-old man, the five-year risk for CVD with the basic
      model was 11.2% (95% CI: 7.8%-15.6%). His metabolic syndrome score, leading to
      1.488 of likelihood ratio, enhanced the risk for CVD up to 15.8% (95% CI: 11.0%
      21.5%) and put him in highest deciles. As with the habit of smoking over 2 packs
      per-day and family history of CVD, yielding the likelihood ratios of 1.62 and
      1.47, respectively, the risk was further raised to 30.9% (95% CI: 20.7%-39.8%).
      CONCLUSIONS: We demonstrate how to make individual risk prediction for CVD by
      incorporating routine information with a sequential Bayesian clinical reasoning
      approach.

PMID- 22658350
TI  - Progression of neurological and cardiovascular disease in left ventricular
      hypertrabeculation/noncompaction.

PMID- 22658351
TI  - Primary carnitine deficiency dilated cardiomyopathy: 28 years follow-up.

PMID- 22658352
TI  - Bidirectional ventricular tachycardia in a patient with acute myocardial
      infarction and aortic stenosis.

PMID- 22658353
TI  - Uric acid: a crucial marker of cardiovascular diseases?

PMID- 22658354
TI  - When should a non-STEMI be treated with primary PCI as for STEMIs?

PMID- 22658355
TI  - A comparative adsorption study of beta-naphthol on four polymeric adsorbents from
      aqueous solutions.
AB  - Adsorptive removal of aromatic compounds from aqueous solutions by polymeric
      adsorbents has attracted many concerns in recent years. A comparative adsorption
      study including equilibria, kinetics and column dynamics of beta-naphthol from
      aqueous solutions was carried out using two hypercrosslinked polymeric adsorbents
      (HJ-1 and TEPA) we developed and two commercial polymeric adsorbents (XAD-4 and
      XAD-7). The adsorption isotherms could be well described by the Freundlich
      equation, and the adsorption equilibrium capacities of beta-naphthol followed an
      order of q(e)((TEPA))>q(e)((HJ-1))>q(e)((XAD-4))>q(e)((XAD-7)). The isosteric
      adsorption enthalpies on HJ-1 and TEPA decreased with increasing adsorption
      fractional loading, while a constant enthalpy was observed for XAD-4 and XAD-7,
      implying that HJ-1 and TEPA had a heterogeneous surface while XAD-4 and XAD-7
      possessed a homogenous surface. The surface energetic heterogeneity of HJ-1 and
      TEPA could be well characterized by the Do's model. The adsorption kinetics were
      fitted by both pseudo-first-order and pseudo-second-order rate equations, and the
      intra-particle diffusion was found to be the rate-limiting step. The adsorption
      breakthrough data were well correlated by the Thomas and Clark models, and the
      dynamic capacities for TEPA, HJ-1, XAD-4 and XAD-7 adsorbents were calculated to
      be 341.7, 321.6, 268.0 and 173.8 mg/g dry resin, which were within 90% of the
      corresponding equilibrium capacities obtained in the batch experiments.

PMID- 22658356
TI  - Local autocatalytic co-precipitation phenomena in self-assembled silica-carbonate
      materials.
AB  - Under certain conditions, precipitation of barium carbonate in alkaline silica
      rich environments affords unusual polycrystalline aggregates exhibiting curved
      shapes and hierarchical structuring, very much reminiscent of biogenic mineral
      tissues. The formation of these so-called silica biomorphs is thought to rely on
      a coupling of chemical equilibria in solution, which drives concerted co
      mineralization and self-assembly of components. In the present work, we have
      studied the effect of fluid motion on morphogenesis by conducting syntheses in
      media stirred at different rates and exposed to an ultrasonic field,
      respectively. The traced growth behavior is discussed on the basis of statistical
      analyses of the occurring morphologies as well as in terms of expected changes in
      the supersaturation of the system. It is shown that the observed complex
      architectures arise as a consequence of an autocatalytic precipitation cycle,
      during which evolving aggregates synthesize and organize their constituents on
      their own upon growth. These processes occur only at a local scale within a
      certain active region that appears to extend over some microns beyond the growth
      front. Our findings provide concrete experimental evidence supporting the
      proposed formation mechanism and suggest that growth of silica biomorphs is
      independent of mass transport from the bulk, unless forced convection becomes
      strong enough to affect the active region and hence interfere with autocatalysis.

PMID- 22658357
TI  - Dielectric spectroscopy of bidisperse colloidal suspensions.
AB  - Dielectric spectroscopy is used to measure the complex permittivity of bidisperse
      colloidal suspensions over the frequency range 2.5 kHz <= omega/2pi <= 10 MHz
      using the spectrometer design of Hollingsworth and Saville (A.D. Hollingsworth,
      D.A. Saville, J. Colloid Interface Sci., 2003). Dielectric spectra of
      monodisperse polystyrene spheres of two diameters (530 nm and 1 MUm) are fit to
      electrokinetic theory using the surface charge density as an adjustable
      parameter. Quantitative agreement is found in the dielectric increment and also
      for the conductivity increment, after considering the effect of added counterions
      and nonspecific adsorption. Bidisperse suspension spectra are a linear
      superposition of each particle's dielectric response. The results provide a
      simple method to extend standard electrokinetic theory based on a single particle
      size to dilute suspensions with many particle sizes and verify the sensitivity of
      the spectrometer.

PMID- 22658358
TI  - Electric conductance of dispersions of metal oxides in solutions of weak acids in
      mixed dioxane-water solvents.
AB  - The electric conductance of solutions of sulfuric, oxalic, benzoic, and salicylic
      acid (up to 0.02 M) in dioxane-water mixed solvents (90% and 93% dioxane by mass)
      has been studied in the presence and absence of TiO(2) and Al(2)O(3) (0.5-5% by
      mass). TiO(2) and Al(2)O(3) enhanced the conductance of solutions of organic
      acids in aqueous dioxane. The conductance is interpreted in terms of adsorption
      of acid in molecular form, dissolution of ceramic oxides in form of anionic
      complexes, and leaching of acidic impurities from ceramic oxides.

PMID- 22658359
TI  - Itraconazole: its possible role in inhibiting angiogenesis in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disorder
      involving mainly synovial joints. It can progress to a severely debilitating form
      with pulmonary, renal and cardiovascular involvement. Currently, disease
      modifying antirheumatic drugs (DMARDs) remain the gold standard pharmacological
      therapy for RA (along with nonsteroidal anti-inflammatory drugs and
      corticosteroids). However, DMARDs are more or less ineffective in the late phase
      of the disease and adverse effects often limit their use. Studies show that serum
      levels of vascular endothelial growth factor (VEGF) remain elevated throughout
      the course of RA. In experimental models, the administration of pro-angiogenic
      cytokines, such as VEGF or FGF, has been shown to increase the severity of the
      disease. Therefore, anti-angiogenic drugs such as bevacizumab (which is already
      being used as an anti-tumor agent) may play a significant role in longstanding
      RA. However, adverse effects such as hypertension, gastro-intestinal perforation
      and the high cost of bevacizumab are major concerns. A recent study suggests that
      itraconazole, an antifungal drug, has a role in selectively inhibiting
      angiogenesis and growth of tumor in non-small cell lung cancer. Hence, this drug
      may be beneficial in the treatment of RA, especially in the later phase when
      other modalities have failed, or as an adjuvant. To test our hypothesis, we
      propose a randomized, double-blinded trial in patients with longstanding RA. The
      control group receives the standard DMARD therapy plus placebo, while the case
      group receives itraconazole in addition to DMARD therapy. Serum and synovial VEGF
      levels, in both the control group and the case group, are compared and their
      correlation with the symptoms is judged. If the VEGF levels are lower and/or the
      symptoms are less severe in the case group, our hypothesis will be confirmed.
      Multi-institutional efforts are needed to confirm this hypothesis, as it is
      relatively new and trial data is limited.

PMID- 22658360
TI  - Metabolomic analysis as biomarker to study steroid hormone administration in
      sepsis.
AB  - Sepsis is a life-threatening disease requiring rapid diagnosis and treatment.
      Steroid hormones (e.g., estradiol, dehydroepiandosterone) have been suggested to
      reduce the hyper-inflammatory response of the immune system and to improve
      outcome in sepsis. We hypothesize that the impact of steroid hormones on the
      metabolic profile (metabolomic fingerprint) can be used to study and guide
      steroid hormone administration in sepsis. Potential biomarker candidates are
      sphingomyelines and phosphatidylcholines.

PMID- 22658361
TI  - Mesenchymal stem cell sheet encapsulated cartilage debris provides great
      potential for cartilage defects repair in osteoarthritis.
AB  - The restoration of the degenerated articular cartilage in patients with
      osteoarthritis (OA) is still a challenge for researchers and clinicians. Drug
      interventions and surgical treatments have been widely attempted for cartilage
      regeneration in OA. However, the results were largely unsatisfactory. Autologous
      chondrocyte implantation (ACI) or matrix-induced autologous chondrocyte
      implantation (MACI) offers potential for the regeneration of cartilage over the
      long-term. However, due to the limitations and disadvantages of ACI, alternative
      therapies for cartilage regeneration are in need. The availability of large
      quantities of mesenchymal stem cells (MSCs) and the multilineage differentiation,
      especially their chondrogenic differentiation property, have made MSCs the most
      promising cell source for cartilage regeneration. In addition, MSCs have been
      shown the ability to undergo site-specific differentiation. MSCs can be obtained
      as MSC sheets using the temperature-responsive culture dish method. The MSC sheet
      can provide amounts of cells and extracellular matrix, which might provide the
      continuity between the implant and host cartilage, thus improving integrative
      cartilage repair. Moreover, OA is associated with progressive and often severe
      inflammation. MSCs not only have the ability to contribute structurally to tissue
      repair, but also possess potent immunomodulatory and anti-inflammatory effects.
      Taken together, these properties make MSC sheet promising candidate for cartilage
      repair in OA. We hypothesize that MSC sheet encapsulated cartilage debris can
      efficiently promote cartilage repair in OA patients. Chondrocytes can be obtained
      and cultured from small cartilage debris in vitro. Therefore, the chondrocytes
      may grow from the debris in cartilage defect and improve cartilage regeneration.
      MSC sheet provide amounts of cells, ECM and protein for cartilage regeneration
      and integration, and may play some roles of periosteum. The operation of MSC
      sheet encapsulated cartilage debris for cartilage repair is simple and practical.
      Moreover, the cell sheet/cartilage debris constructs can be easily shaped based
      on the size and shape of cartilage defects. The new method might have great
      potential in treating cartilage defects clinically, especially for OA patients.

PMID- 22658362
TI  - MicroRNA changes in advanced radiotherapy techniques and its effect to secondary
      cancers.
AB  - MicroRNAs (miRNAs) are a kind of RNA, produced copies of endogenous hairpin
      shaped, are 21-25 nucleotide length, small, and single chain. Recent studies have
      revealed that hundreds of miRNAs are found in the human genome and are
      responsible for diverse cellular processes including the control of developmental
      timing, cell proliferation, apoptosis and tumorigenesis. miRNAs can activate the
      initiation of apoptosis, cessation of the cell cycle and aging in case of DNA
      damage by stimulating the tumor suppressor target gene p53 directly and
      indirectly. DNA damage is composed by multiple stress factors including ionizing
      radiation, reactive oxygen species, UV exposure and drugs like doxorubicin and
      camptothecin. Radiation is used widely in health, academic area, and industry for
      producing electricity. As a result of using radiation widely in different fields,
      environmental radiation exposure is increasing as well. Whereas high dose
      radiation exposure causes DNA damage and gives rise to ionization to molecules of
      living cells by accelerating malignant tumor formation. Fields receiving high
      dose radiation are evaluated in terms of adverse effects, therapeutic efficacy
      and secondary malignancies in radiotherapy applications. Dose distributions are
      re-created when it is required. On the other hand, fields received low dose and
      the doses that the patient is exposure in simulation and/or portal imaging are
      often overlooked. The changes in miRNA levels arising in low dose radiation field
      and its effect to neoplastic process in cell will be pathfinder in terms of
      secondary cancers or second primary cancers. It is shown that there are
      differences between the level changes of miRNA in low dose fields which are
      overlooked in daily practical applications because of not resulting with acute or
      chronic side effect and the level changes of miRNA in high dose fields. With the
      help of verifying so-called differences in low dose fields which are seen in
      advanced radiation techniques, radiation oncologists must be careful when using
      these techniques in childhood cancers and the patient group which have long
      overall survival period. Additionally, demonstrating the pathway which is
      influenced by miRNA changes can provide us the opportunity to focus on the exact
      cancer type which has to be followed. So that we can detect the secondary cancers
      earlier and can treat them with long expected survival period.

PMID- 22658363
TI  - Regioselective synthesis and antimicrobial studies of ester linked 1,4
      disubstituted 1,2,3-bistriazoles.
AB  - A series of 1,4-disubstituted 1,2,3-bistriazoles was synthesized via click
      chemistry by cycloaddition of various bisalkynes with benzyl/2-phenylethyl azide.
      Synthesized triazoles were characterized by IR, (1)H NMR, (13)C NMR and mass
      spectral techniques. All the compounds were evaluated for
      antibacterial/antifungal activities and found to possess moderate to good
      antimicrobial activities. Further the docking study for the most active compound
      against DNA Gyrase was also carried out.

PMID- 22658364
TI  - Double protein knockdown of cIAP1 and CRABP-II using a hybrid molecule consisting
      of ATRA and IAPs antagonist.
AB  - Protein knockdown can be achieved by the use of a small molecule that possesses
      affinity for both the target protein and ubiquitin ligase. We have designed such
      a degradation-inducing molecule targeting cIAP1 and CRABP-II, which are involved
      in proliferation of several cancer cell lines and in neuroblastoma growth,
      respectively. As a CRABP-II-recognizing moiety, all-trans retinoic acid (ATRA,
      3), a physiological ligand of CRABP, was chosen. As a cIAP1-recognizing moiety,
      MV1 (5), which is a cIAP1/cIAP2/XIAP pan-ligand, was chosen. Although cIAP1
      itself possesses ubiquitin ligase activity, we expected that its decomposition
      would be efficiently mediated by related molecules, including cIAP2 and XIAP,
      which also possess ubiquitin ligase activity. The designed degradation inducer 6,
      in which ATRA (3) and MV1 (5) moieties are connected via a linker, was
      synthesized and confirmed to induce efficient degradation of both cIAP1 and CRABP
      II. It showed potently inhibited the proliferation of IMR32 cells.

PMID- 22658365
TI  - Synthesis and cytotoxic activity of 4-N-carboxybutyl-5-fluorocytosyl-Arg-Gln-Trp
      Arg-Arg-Trp-Trp-Gln-Arg-NH2.
AB  - The chemical synthesis of 4-N-carboxybutyl-5-fluorocytosine (II) in solution
      phase starting from 5-fluorocytosine and the solid phase synthesis of Arg-Gln-Trp
      Arg-Arg-Trp-Trp-Gln-Arg-NH(2) attached to the 4-N-carboxybutyl-5-fluorocytosine
      residue at the N-terminus of the peptide (III) via peptide bond formation is
      reported. The target compound exhibited a significant cytotoxic activity against
      a culture of HepG2 cells. In addition our results demonstrated that this new
      compound affect cell viability, produce mitochondrial dysfunction as well as
      interfere with intracellular calcium homeostasis control; leading to cell
      malfunction and death.

PMID- 22658366
TI  - The paradox of interprofessional education: IPE as a mechanism of maintaining
      physician power?

PMID- 22658367
TI  - Non-arginine-aspartate (non-RD) kinases are associated with innate immune
      receptors that recognize conserved microbial signatures.
AB  - An important question in the field of plant-pathogen interactions is how the
      detection of pathogens is converted into an effective immune response. In recent
      years, substantial insight has been gained into the identities of both the plant
      receptors and the microbial molecules they recognize. Likewise, many of the
      downstream signaling proteins and transcriptions factors that activate defense
      responses have been characterized. However, the early molecular events that
      comprise 'recognition' and how defense signaling specificity is achieved are not
      as well understood. In this review we discuss the significance of non-arginine
      aspartate (non-RD) kinases, a subclass of kinases that are often found in
      association with pattern recognition receptors (PRRs).

PMID- 22658368
TI  - Iron overload and toxicity: implications for anesthesiologists.
AB  - Conditions leading to iron overload range from rare hereditary disorders to more
      common medical conditions associated with chronic blood transfusions. Iron
      overload has deleterious effects on various vital organs (eg, liver, heart, and
      endocrine glands). Serum ferritin (in conjunction with transferrin saturation) is
      the most widely used test to evaluate iron burden and to screen for iron
      overload. The management plan should be adjusted to account for iron overload and
      potential consequences of liver, heart, and other organ involvement.

PMID- 22658369
TI  - The GlideScope for videolaryngoscopy-assisted nasotracheal-to-orotracheal tube
      exchange in the intensive care unit in a patient with a known difficult airway.
AB  - A 77 year old, nasally intubated man with a history of repeated episodes of
      airway obstruction requiring intubation due to recurrent laryngitis and a
      hypopharyngeal mass, needed nasotracheal-to-orotracheal tube exchange. The
      GlideScope videolaryngoscope was inserted, achieving a full view of the glottic
      inlet with the nasotracheal tube in situ. An endotracheal tube (ETT) loaded on a
      GlideRite Rigid Stylet was advanced through the oropharynx into view. Advancement
      of this ETT to the glottic opening was tested and achieved. With both tracheal
      tubes in view, the nasotracheal tube cuff was deflated and withdrawn from the
      glottic opening. While maintaining videoscopic visualization, the orotracheal
      tube was advanced through the vocal cords into the trachea. The benefits of this
      technique versus existing alternatives are discussed.

PMID- 22658370
TI  - Isoflurane hepatitis-induced liver failure: a case report.
AB  - A case of fulminant hepatic failure two days following an uneventful operation
      during isoflurane anesthesia is presented. Investigations included elevated
      bilirubin and serum transaminases in the absence of any other cause of hepatic
      dysfunction. The patient died on the fourth postoperative day. Subsequent
      postmortem examination showed centrilobular coagulative necrosis consistent with
      drug toxicity, with isoflurane as the most likely toxic agent.

PMID- 22658371
TI  - Sodium-reduced continuous venovenous hemodiafiltration (CVVHDF) for the
      prevention of central pontine myelinolysis (CPM) in hyponatremic patients
      scheduled for orthotopic liver transplantation.
AB  - Two patients in end-stage hepatic failure presented for orthotopic liver
      transplantation with longstanding severe hyponatremia (121 and 122 mmol/L). Both
      patients underwent liver transplantation with the concomitant use of continuous
      venovenous hemodiafiltration. Replacement and dialysate solutions were prepared
      individually to contain a sodium level that was individually considered safe with
      regard to the development of central pontine myelinolysis. The sodium increase in
      both patients was within the expected and planned limits despite a situation of
      mass transfusion. Both patients did well postoperatively and neither patient
      suffered neurological deficits.

PMID- 22658372
TI  - Vascular pediatric interventional radiology.
AB  - Interventional radiology procedures are increasingly in demand in both the adult
      and pediatric populations. Pediatric procedures mirror many of the adult
      procedures but with increased complexity due to many considerations, notably
      patient size. This article reviews the various vascular pediatric interventional
      procedures. The aim is to provide a greater exposure to the possible treatment
      options for pediatric patients and to facilitate understanding of the success and
      complications rates related to various interventions.

PMID- 22658373
TI  - Health care delivery through a different lens: the lived experience of culture
      shock while participating in an international educational program.
AB  - An international educational experience can enhance the curriculum of an
      undergraduate program in nursing and can promote student development. However,
      many students who participate in international programs experience the
      debilitating effects of symptoms that comprise a phenomenon that is sometimes
      labeled culture shock. The progress of American nursing students through the
      stages of adaptation to a different culture is examined through journal entries
      the students recorded while they were in England for a short-term experience in
      community health nursing. The benefits of participation in an international
      program are discussed. Also included are guidelines for faculty to help them
      recognize the symptoms described and to implement appropriate interventions.

PMID- 22658374
TI  - Development and interrater reliability testing of a telephone interview training
      programme for Australian nurse interviewers.
AB  - BACKGROUND: The final phase of a three phase study analysing the implementation
      and impact of the nurse practitioner role in Australia (the Australian Nurse
      Practitioner Project or AUSPRAC) was undertaken in 2009, requiring nurse
      telephone interviewers to gather information about health outcomes directly from
      patients and their treating nurse practitioners. A team of several registered
      nurses was recruited and trained as telephone interviewers. The aim of this paper
      is to report on development and evaluation of the training process for telephone
      interviewers. METHODS: The training process involved planning the content and
      methods to be used in the training session; delivering the session; testing
      skills and understanding of interviewers post-training; collecting and analysing
      data to determine the degree to which the training process was successful in
      meeting objectives and post-training follow-up. All aspects of the training
      process were informed by established educational principles. RESULTS: Interrater
      reliability between interviewers was high for well-validated sections of the
      survey instrument resulting in 100% agreement between interviewers. Other
      sections with unvalidated questions showed lower agreement (between 75% and 90%).
      Overall the agreement between interviewers was 92%. Each interviewer was also
      measured against a specifically developed master script or gold standard and for
      this each interviewer achieved a percentage of correct answers of 94.7% or
      better. This equated to a Kappa value of 0.92 or better. CONCLUSION: The
      telephone interviewer training process was very effective and achieved high
      interrater reliability. We argue that the high reliability was due to the use of
      well validated instruments and the carefully planned programme based on
      established educational principles. There is limited published literature on how
      to successfully operationalise educational principles and tailor them for
      specific research studies; this report addresses this knowledge gap.

PMID- 22658376
TI  - Thrombin generation in rheumatoid arthritis.

PMID- 22658375
TI  - Efficacy of anakinra for refractory acute calcium pyrophosphate crystal
      arthritis.
AB  - Acute synovitis induced by deposition of calcium pyrophosphate (CPP) and
      monosodium urate crystals involves interleukin-1beta production and activation.
      The efficacy of blocking interleukin-1beta activity (with an interleukin-1
      receptor antagonist [anakinra] or interleukin-1beta antibody) is well documented
      for gout attacks but has only been reported in two single-case reports of CPP
      crystal-induced acute arthritis. Here we report on five cases (four males, mean
      age 71+/-27) of CPP crystal-induced inflammatory arthritis refractory and/or
      intolerant to usual drug therapy and efficiently treated with anakinra. Diagnosis
      of CPP crystal-induced arthritis was confirmed by identification of crystals in
      synovial fluid. CPP crystal-induced oligo-arthritis (n=4) and polyarthritis (n=1)
      were refractory to conventional treatments, including non-steroidal anti
      inflammatory drugs, colchicine and steroids (systemic administration or intra
      articular injection). After latent infection was ruled out, anakinra, 100mg/day,
      was administered subcutaneously for 3 days. Four patients showed rapid clinical
      and biological responses at a mean of 3 days after treatment. Anakinra provided
      good joint pain relief (baseline 0-100mm visual analog scale score 60+/-17mm,
      outcome 10+/-10mm) and decreased serum C-reactive protein level (58+/-43 to 5+/
      2mg/L). Anakinra was well tolerated. One injection-site skin reaction was
      observed but no infection. Anakinra was effective and safe in this small series
      of patients with refractory arthritis due to acute CPP crystal deposition.

PMID- 22658377
TI  - Transcriptional response to GAA deficiency (Pompe disease) in infantile-onset
      patients.
AB  - Pompe disease is a genetic disorder resulting from a deficiency of lysosomal acid
      alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to
      symptom severity and rate of progression. In this study, we used microarrays to
      examine gene expression from the muscle of two cohorts of infantile-onset Pompe
      patients to identify transcriptional differences that may contribute to the
      disease phenotype. We found strong similarities among the gene expression
      profiles generated from biceps and quadriceps, and identified a number of
      signaling pathways altered in both cohorts. We also found that infantile-onset
      Pompe patient muscle had a gene expression pattern characteristic of immature or
      regenerating muscle, and exhibited many transcriptional markers of inflammation,
      despite having few overt signs of inflammatory infiltrate. Further, we identified
      genes exhibiting correlation between expression at baseline and response to
      therapy. This combined dataset can serve as a foundation for biological discovery
      and biomarker development to improve the treatment of Pompe disease.

PMID- 22658378
TI  - Maintenance of clinical efficacy after dose reduction of ixabepilone plus
      capecitabine in patients with anthracycline- and taxane-resistant metastatic
      breast cancer: a retrospective analysis of pooled data from 2 phase III
      randomized clinical trials.
AB  - BACKGROUND: This retrospective analysis aimed to determine whether early dose
      reduction impacts the efficacy of ixabepilone plus capecitabine in women with
      metastatic breast cancer (MBC). PATIENTS AND METHODS: In 2 phase III trials,
      patients (N = 1973) with anthracycline/taxane-pretreated MBC were randomized to
      receive ixabepilone 40 mg/m(2) on day 1 plus capecitabine 1000 mg/m(2) twice
      daily (BID) on days 1 to 14 or single-agent capecitabine 1250 mg/m(2) BID on days
      1 to 14 of a 3-week course. Because of the similar design and populations, data
      from trials were pooled to evaluate efficacy of the combination regimen among
      women who did or did not undergo ixabepilone dose reduction during the first 4
      courses. To adjust for bias resulting from selecting patients with inherently
      better outcome based on longer treatment durations, these analyses were
      restricted to patients who received >= 4 courses of ixabepilone. RESULTS: The
      pooled cohort included 566 patients with measurable disease who were evaluable
      for efficacy. Patients who had early dose reduction showed similar objective
      response rates (ORRs) and progression-free survival (PFS) as did those with
      no/late dose reduction. ORRs were 62.6% (95% confidence interval [CI], 55.8%
      69.0%) and 55.3% (95% CI, 49.9%-60.6%), respectively; median PFS was 7.2 months
      (95% CI, 6.6-8.0) and 7.0 months (95% CI, 6.5-7.5), respectively (hazard ratio =
      0.98; 95% CI, 0.83-1.17). CONCLUSION: These data suggest that early ixabepilone
      dose reduction did not affect the overall efficacy of ixabepilone plus
      capecitabine in patients with MBC who received >= 4 courses of treatment. By
      making appropriate dose reductions, ixabepilone-related toxicities can be
      minimized while maintaining clinical efficacy.

PMID- 22658380
TI  - Evaluation of a newborn with a murmur.

PMID- 22658379
TI  - Recruitment strategies and rates of a multi-site behavioral intervention for
      adolescents and young adults with cancer.
AB  - INTRODUCTION: To provide an overview of factors related to recruitment of
      adolescents and young adults (AYA) into research and recruitment rates and
      reasons for refusal from a multicenter study entitled "Stories and Music for
      Adolescent/Young Adult Resilience during Transplant" (SMART). METHODS: A
      randomized clinical trial study design was used. The settings included 9
      hospitals. The sample included AYAs (aged 11-24 years) who were undergoing a stem
      cell transplant. Several instruments were used to measure symptom distress,
      coping, resilience, and quality of life in AYA with cancer. RESULTS: A total of
      113 AYA were recruited (50%) for this study. Strategies were refined as the study
      continued to address challenges related to recruitment. We provide a description
      of recruitment strategies and an evaluation of our planning, implementing, and
      monitoring of recruitment rates for the SMART study. DISCUSSION: When designing a
      study, careful consideration must be given to factors influencing recruitment as
      well as special considerations for unique populations. Dissemination of
      strategies specific to unique populations will be helpful to the design of future
      research studies.

PMID- 22658381
TI  - Recommendations for the practice of travel medicine.
AB  - Travel Medicine has emerged as a distinct entity over the last two decades in
      response to a very substantial increase in international travel and is now
      forging its own identity, remit and objectives for care of the traveller. Crucial
      to the formation of any speciality is the definition of recommendations for its
      practice. This is particularly important and needed for travel medicine as it
      overlaps with and forms part of day-to-day work in a number of different medical
      specialities. This document defines a set of recommendations for the practice of
      travel medicine from the Faculty of Travel Medicine of the Royal College of
      Physicians and Surgeons of Glasgow. Their objective is to help raise standards of
      practice and achieve greater uniformity in provision of services, better to
      protect those who travel. As travel medicine moves towards applying for
      speciality status, these standards will also contribute to that process.

PMID- 22658382
TI  - pERK activation in esophageal carcinomas: clinicopathological associations.
AB  - MAPK (mitogen-activated protein kinase) pathway is considered a control regulator
      in various malignant tumors but its role in esophageal carcinomas remains
      elusive. In our study, we examined the possible prognostic significance of MAPK
      pathway in human esophageal cancer. We searched for mutations in exons 18-21 of
      EGFR gene, codons 12 and 13 of K-RAS gene and exon 15 of B-RAF gene by high
      resolution melting analysis (HRMA) and pyrosequencing in 44 esophageal
      carcinomas. Immunohistochemistry was performed in 29 cases in order to evaluate
      expression levels of pERK (extracellular-signal regulated kinase). In one laser
      microdissected squamous cell carcinoma, a somatic K-RAS mutation at codon 12 was
      detected, whereas none of the cases displayed mutations in EGFR and B-RAF genes.
      Elevated nuclear as well as cytoplasmic pERK expression (100% and 62% of cases
      respectively) was observed independently of EGFR and B-RAF mutational status.
      Increasing pERK nuclear and cytoplasmic expression as well as the intensity of
      nuclear staining was found to be significantly correlated with tumor grade in
      univariate and multivariate statistical analysis. Our findings depict the
      presence of activated ERK despite the low frequency of upstream alterations,
      implicating ERK activation in the acquisition of a more aggressive phenotype in
      esophageal cancer.

PMID- 22658383
TI  - Unusual B cell morphology in inflammatory bowel disease.
AB  - B lymphocytes express various different types of surface immunoglobulins that are
      largely unrelated to other hematological lines, although some reports have
      described a relationship between malignant B cells and other cells such as
      macrophages. Multiple genes of hematopoietic lineage, including transcription
      factors, are co-expressed in hematopoietic stem cells and progenitors, a
      phenomenon referred to as "lineage priming". Changes in the expression levels and
      timing of transcription factors can induce the lineage conversion of committed
      cells, which indicates that the regulation of transcription factors might be
      particularly critical for maintaining hierarchical hematopoietic development. The
      aim of this study was to evaluate the surface markers of particular IgM-positive
      and irregularly nucleated cells detected in patients with inflammatory bowel
      disease (IBD), and to assess their association with diagnosis and inflammatory
      cell recruitment. Small intestine, colon and rectal biopsy specimens of 96 IBD
      patients were studied. Immunoglobulin-producing cells (IPCs) were analyzed by
      means of immunofluorescence using polyclonal rabbit anti-human Ig and goat anti
      human IgM. The specimens positive for B cells with irregular nuclei were assessed
      using monoclonal antibodies specific for CD79, and lambda and kappa chains in
      order to confirm their B cell nature. CD15+ cells, an important marker of
      inflammatory cell recruitment, were also evaluated. Statistical correlations were
      sought between the histological findings and clinical expression. 34 (35.4%) of
      the 96 patients (64 with ulcerative colitis and 32 with Crohn's disease)
      presented a periglandial localization of IPCs with irregular nuclei, which showed
      surface markers specific for the B cell subset, such as IgM and CD79, but
      quantitative differences in lambda and kappa chains. These specimens also
      contained CD15-positive cells, which are usually absent in healthy controls. The
      quantitative aspects and localization of the CD15-positive cells correlated with
      the distribution of the IPCs with irregular nuclei. IPCs with irregular nuclei
      were significantly more frequent in those patients with Crohn's disease than in
      those with ulcerative colitis (p<0.001). The finding of a subpopulation of cells
      that simultaneously showed irregular nuclei and B cell markers, such as
      functional surface IgM, in patients with IBD suggests that an unusual subgroup of
      B cells that correlates with CD15 expression and a diagnosis of Crohn's disease
      may be observed in the inflammatory process.

PMID- 22658384
TI  - Intracranial meningeal carcinomatosis in metastatic castration resistant prostate
      cancer: will extension of survival increase the incidence?

PMID- 22658385
TI  - Dose matters: the importance of appropriate dosing: a case report on sunitinib
      treatment in a patient with metastatic renal cell carcinoma.

PMID- 22658386
TI  - Effect of colonoscopy on colorectal cancer incidence and mortality: an
      instrumental variable analysis.
AB  - BACKGROUND: Using population-based health services information to estimate the
      effectiveness of colonoscopy on colorectal cancer (CRC) outcomes is prone to
      selection bias. OBJECTIVE: To determine the effect of colonoscopy on CRC
      incidence and mortality. DESIGN: Population-based retrospective cohort study.
      SETTING: Ontario provincial health data information. PATIENTS: This study
      involved average-risk persons aged 50 to 74 years from 1996 to 2000 who were
      alive and free of CRC on January 1, 2001. INTERVENTION: Colonoscopy between 1996
      and 2000. MAIN OUTCOME MEASUREMENTS: CRC incidence and mortality from 2001 to
      2007. RESULTS: The study cohort contained 1,089,998 persons, 7.9% of whom had
      undergone a colonoscopy between 1996 and 2000. Using primary care physician rate
      of discretionary colonoscopy as an instrumental variable, the receipt of
      colonoscopy was associated with a 0.60% (95% confidence interval [CI], 0.31%
      0.78%) absolute reduction in the 7-year colorectal cancer incidence and a 0.17%
      (95% CI, 0.14%-0.21%) absolute reduction in the 5-year risk of death caused by
      CRC. This corresponds to a 48% relative decrease in CRC incidence (risk ratio
      [RR] 0.52; 95% CI, 0.34-0.76) and 81% decrease in mortality caused by CRC (RR
      0.19, 95% CI, 0.07-0.47). In subgroup analyses, the reduction in the risk of
      death due to CRC was larger in women than men. The reduction in CRC incidence was
      larger for complete colonoscopies and for left-sided cancers. LIMITATIONS:
      Instrumental variable methods estimate only the marginal effect on the population
      studied. CONCLUSION: Increased use of colonoscopy procedures is associated with a
      reduction in the incidence and mortality of CRC in the population studied.

PMID- 22658387
TI  - Diagnostic significance of a dilated orifice of the duodenal papilla in
      intraductal papillary mucinous neoplasm of the pancreas.
AB  - BACKGROUND: A dilated orifice of the duodenal papilla found during screening
      endoscopy or ERCP is well-known as one of the specific findings of intraductal
      papillary mucinous neoplasm (IPMN). However, its clinical significance is still
      unclear. OBJECTIVE: To assess the diagnostic significance of a dilated orifice of
      the duodenal papilla and evaluate whether this could be a factor predictive of
      malignancy or a subtype of IPMN. DESIGN: Retrospective study. SETTING: University
      hospital. PATIENTS: This study involved 149 patients who underwent pancreatectomy
      for IPMN between January 1987 and June 2011. INTERVENTION: ERCP. MAIN OUTCOME
      MEASUREMENTS: The rate of malignant and intestinal type IPMNs in patients with
      and without papillary dilation. RESULTS: A dilated orifice of the duodenal
      papilla was significantly associated with intestinal type IPMN (P < .001), but
      this finding could not predict the malignant grade of IPMN (P = .13).
      Multivariate analysis revealed that a dilated orifice was a significant factor
      for predicting intestinal type in both main duct (P = .01) and branch duct IPMNs
      (P < .001). LIMITATIONS: The validity of the definition of papillary dilation,
      selection bias, and a retrospective study. CONCLUSION: A dilated orifice of the
      duodenal papilla could be a significant factor for predicting intestinal type
      IPMN. This may lead to better clinical management of patients with IPMN.

PMID- 22658388
TI  - Use of a novel endoscopic suturing device to treat recalcitrant marginal
      ulceration (with video).

PMID- 22658389
TI  - Randomized trial comparing the 22-gauge aspiration and 22-gauge biopsy needles
      for EUS-guided sampling of solid pancreatic mass lesions.
AB  - BACKGROUND: To overcome limitations of cytology, biopsy needles have been
      developed to procure histologic samples during EUS. OBJECTIVE: To compare 22
      gauge (G) FNA and 22G biopsy needles (FNB) for EUS-guided sampling of solid
      pancreatic masses. DESIGN: Randomized trial. SETTING: Tertiary-care medical
      center. PATIENTS: This study involved 56 patients with solid pancreatic masses.
      INTERVENTION: Sampling of pancreatic masses by using 22G FNA or 22G FNB devices.
      MAIN OUTCOME MEASUREMENTS: Compare the median number of passes required to
      establish the diagnosis, diagnostic sufficiency, technical performance,
      complication rates, procurement of the histologic core, and quality of the
      histologic specimen. RESULTS: A total of 28 patients were randomized to the FNA
      group and 28 to the FNB group. There was no significant difference in median
      number of passes required to establish the diagnosis (1 [interquartile range 1
      2.5] vs 1 [interquartile range 1-1]; P = .21), rates of diagnostic sufficiency
      (100% vs 89.3%; P = .24), technical failure (0 vs 3.6%; P = 1.0), or
      complications (3.6% for both) between FNA and FNB needles, respectively. Patients
      in whom diagnosis was established in passes 1, 2, and 3 were 64.3% versus 67.9%,
      10.7% versus 17.9%, and 25% versus 3.6%, respectively, for FNA and FNB cohorts.
      There was no significant difference in procurement of the histologic core (100%
      vs 83.3%; P = .26) or the presence of diagnostic histologic specimens (66.7% vs
      80%; P = .66) between FNA and FNB cohorts, respectively. LIMITATIONS: Only
      pancreatic masses were evaluated. CONCLUSION: Diagnostic sufficiency, technical
      performance, and safety profiles of FNA and FNB needles are comparable. There was
      no significant difference in yield or quality of the histologic core between the
      2 needle types.

PMID- 22658391
TI  - Pleural effusion caused by a pancreatic pleural fistula.

PMID- 22658390
TI  - Immediate unprepared hydroflush colonoscopy for severe lower GI bleeding: a
      feasibility study.
AB  - BACKGROUND: Urgent colonoscopy is not always the preferred initial intervention
      in severe lower GI bleeding because of the need for a large volume of oral bowel
      preparation, the time required for administering the preparation, and concern
      regarding adequate visualization. OBJECTIVE: To evaluate the feasibility, safety,
      and outcomes of immediate unprepared hydroflush colonoscopy for severe lower GI
      bleeding. DESIGN: Prospective feasibility study of immediate colonoscopy after
      tap-water enema without oral bowel preparation, aided by water-jet pumps and
      mechanical suction devices in patients admitted to the intensive care unit with a
      primary diagnosis of severe lower GI bleeding. SETTING: Tertiary referral center.
      MAIN OUTCOME MEASUREMENTS: Primary outcome measurement was the percentage of
      colonoscopies in which the preparation permitted satisfactory evaluation of the
      entire length of the colon suspected to contain the source of bleeding. Secondary
      outcome measurements were visualization of a definite source of bleeding, length
      of hospital and intensive care unit (ICU) stays, rebleeding rates, and
      transfusion requirements. RESULTS: Thirteen procedures were performed in 12
      patients. Complete colonoscopy to the cecum was performed in 9 of 13 patients
      (69.2%). However, endoscopic visualization was thought to be adequate for
      definitive or presumptive identification of the source of bleeding in all
      procedures, with no colonoscopy repeated because of inadequate preparation. A
      definite source of bleeding was identified in 5 of 13 procedures (38.5%). The
      median length of ICU stay was 1.5 days; of hospital stay, 4.3 days. Recurrent
      bleeding during the same hospitalization, requiring repeated endoscopy, surgery,
      or angiotherapy, was seen in 3 of 12 patients (25%). LIMITATIONS: Uncontrolled
      feasibility study of selected patients. CONCLUSION: Immediate unprepared
      hydroflush colonoscopy in patients with severe lower GI bleeding is feasible with
      the hydroflush technique.

PMID- 22658392
TI  - Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical
      performance at older ages: an individual participant meta-analysis.
AB  - The association between functioning of the hypothalamic pituitary adrenal (HPA)
      axis and physical performance at older ages remains poorly understood. We carried
      out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as
      indexed by patterns of diurnal cortisol release, is associated with worse
      physical performance. Data from six adult cohorts (ages 50-92 years) were
      included in a two stage meta-analysis of individual participant data. We analysed
      each study separately using linear and logistic regression models and then used
      meta-analytic methods to pool the results. Physical performance outcome measures
      were walking speed, balance time, chair rise time and grip strength. Exposure
      measures were morning (serum and salivary) and evening (salivary) cortisol. Total
      sample sizes in meta-analyses ranged from n=2146 for associations between morning
      Cortisol Awakening Response and balance to n=8448 for associations between
      morning cortisol and walking speed. A larger diurnal drop was associated with
      faster walking speed (standardised coefficient per SD increase 0.052, 95%
      confidence interval (CI) 0.029, 0.076, p<0.001; age and gender adjusted) and a
      quicker chair rise time (standardised coefficient per SD increase -0.075, 95% CI 
      0.116, -0.034, p<0.001; age and gender adjusted). There was little evidence of
      associations with balance or grip strength. Greater diurnal decline of the HPA
      axis is associated with better physical performance in later life. This may
      reflect a causal effect of the HPA axis on performance or that other ageing
      related factors are associated with both reduced HPA reactivity and performance.

PMID- 22658393
TI  - Stability of the diurnal cortisol profile in children and adolescents.
AB  - The diurnal cortisol profile has been implicated in multiple physical and mental
      health conditions in children and adolescents; however, current knowledge
      regarding the stability of the diurnal cortisol profile is largely based on
      adults. Developmental changes throughout childhood and adolescence warrant
      examination of the stability of the diurnal cortisol profile during this stage in
      the lifecourse. The aim of the present study was to conduct a comprehensive
      evaluation of the diurnal cortisol profile in children and adolescents.
      Participants (N=233; M=12.40, SD=1.83; 44.2% girls) in the Healthy Heart Project
      collected saliva samples, completed demographic questionnaires, and recorded bed
      and waking time. Intra-class correlations were calculated to evaluate the
      stability of aggregate and single sample measures of the diurnal cortisol
      profile. Total cortisol concentration (AUC(TG), AUC(AG)) and maximum sample were
      the most stable cortisol measures (ICC(avg)=0.54). Dynamic measures (AUC(I),
      slope; ICC(avg)=0.22) and other single sample measures (awake, lunch, dinner,
      bedtime, morning random, day random; ICC(avg)=0.28) were less stable. Of the
      developmentally relevant covariates tested, sleep duration, adrenarche, and time
      of awakening were most associated with cortisol values. Altogether, the diurnal
      cortisol profile yielded moderate to high stability in children and adolescents.
      These findings can inform methodological decisions regarding cortisol sampling
      protocols for children and adolescents.

PMID- 22658394
TI  - [Unexpected difficult airway in a patient during shoulder arthroscopy with
      general anaesthesia and interscalene brachial plexus block].

PMID- 22658395
TI  - [Delayed post-operative epileptic seizure after carotid endarterectomy: a case of
      cerebral hyperperfusion syndrome?].
AB  - The so-called cerebral hyperperfusion syndrome is basically due to a lack of
      cerebral autoregulation, inability to control the restoring of flow after
      revascularisation surgery. It present clinically as intense migraine, epileptic
      seizures, or neurological focality. It may even progress to an intracerebral
      haemorrhage. It usually appears a few days after surgery. We present the case of
      a patient subjected to a carotid endarterectomy, who had an epileptic episode in
      the late post-operative period. We attributed a cerebral hyperperfusion syndrome
      as the most likely cause. Knowledge of this syndrome may help to correctly
      orientate and treat the neurological complications that appear after this type of
      surgery.

PMID- 22658396
TI  - [Osteochondroplastic tracheobronchopathy: an unexpected difficult airway].

PMID- 22658397
TI  - [Delayed iatrogenic tracheal post-intubation rupture. A short review of the
      aetiopathology and treatment].
AB  - Iatrogenic tracheal rupture is a rare complication with a high morbidity and
      mortality. Tracheal intubation is the main cause and its origin is
      multifactorial. The diagnosis is based on non-specific but highly suggestive
      signs and symptoms, such as subcutaneous emphysema, pneumothorax, respiratory
      distress, or haemoptysis. Confirmation of the diagnosis requires an examination
      by bronchoscopy. Surgical repair has traditionally been the treatment of choice
      although the current trend is conservative management.

PMID- 22658398
TI  - [Bicytopenia associated with the delivery a dead foetus of 32 weeks].

PMID- 22658399
TI  - [Perioperative tumour dissemination. 1. Influence of perioperative factors].
AB  - There has been growing concern in the last few years on the effect of anaesthetic
      drugs used during oncological surgery could have on tumour progression in the
      long-term, as well as the influence of other perioperative factors. Although much
      of the available data has weak evidence, the role of the surgery itself, pain,
      transfusion of blood derivatives, etc., have been assessed in several studies.
      How some substances used during the anaesthetic process can influence tumour
      immune surveillance, cell proliferation or tumour angiogenesis processes have
      been observed in laboratory studies. The possible relevance of the anaesthetic
      technique used as regards the long-term tumour progression and survival is still
      to be determined. However, based on retrospective studies, it seems that those
      anaesthetic techniques combined with the use of regional anaesthesia and
      analgesia could be beneficial compared to those that are maintained on opioid
      use. Further research should help to elucidate the long-term clinical relevance
      of the perioperative procedures, including the anaesthetic, during oncological
      surgery.

PMID- 22658400
TI  - PAOPA, a potent dopamine D2 receptor allosteric modulator, prevents and reverses
      behavioral and biochemical abnormalities in an amphetamine-sensitized preclinical
      animal model of schizophrenia.
AB  - Allosteric modulators are emerging as new therapeutics for the treatment of
      psychiatric illnesses, such as schizophrenia. Conventional antipsychotic drugs
      are typically dopamine D2 receptor antagonists that compete with endogenous
      dopamine at the orthosteric site, and block excessive dopamine neurotransmission
      in the brain. However, they are unable to treat all symptoms of schizophrenia and
      often cause adverse motor and metabolic side effects. The binding profile of
      allosteric modulators differs, as they interact with their receptor at a novel
      binding site and their activity is determined by physiological signaling. In
      collaboration, our laboratories have synthesized and evaluated over 185 compounds
      for their allosteric modulatory activity at the dopamine D2 receptor. Of these
      compounds, PAOPA is among the most potent allosteric modulators, and has been
      shown to be effective in treating the MK-801 induced preclinical animal model of
      schizophrenia. The objective of this study was to evaluate PAOPA's ability to
      prevent and reverse behavioral abnormalities in an amphetamine-sensitized
      preclinical animal model of schizophrenia. Amphetamine sensitized rats were given
      PAOPA during sensitization and following sensitization to determine whether PAOPA
      is able to prevent and reverse behavioral abnormalities. Furthermore, changes in
      post-mortem dopamine levels were measured by high performance liquid
      chromatography in various brain regions. The results presented demonstrate that
      PAOPA is able to prevent and reverse behavioral and biochemical abnormalities in
      an amphetamine-sensitized animal model of schizophrenia.

PMID- 22658402
TI  - [2012 Congress of International Society for the Study of Women's Sexual Health
      (ISSWSH), 19-22 February, Jerusalem, Israel].

PMID- 22658401
TI  - Dual orexin receptor antagonism by almorexant does not potentiate impairing
      effects of alcohol in humans.
AB  - The orexin system plays a pivotal role in the regulation of the sleep/wake state.
      Almorexant is a selective, orally available dual orexin receptor antagonist. This
      study evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) interactions
      between almorexant (200 mg p.o.) and alcohol (0.6 g/L i.v. ethanol clamp for 5 h)
      using various cognitive and psychomotor performance tests in healthy subjects
      (n=20; 10 males and 10 females) in a 4-way crossover study. No effect of
      almorexant on ethanol PK was observed. The effects of ethanol on the PK of
      almorexant were limited, its exposure (AUC) increased by 21%; the median
      difference in tmax was 1.2 h; t1/2 and Cmax of almorexant were unchanged.
      Almorexant showed decreases in adaptive tracking performance, saccadic peak
      velocity, and subjective alertness as assessed by visual analog scale (VAS) of
      Bond and Lader, but had no or small effects on smooth pursuit eye movements, body
      sway, VAS for alcohol intoxication, and a memory test. Almorexant administered
      together with ethanol showed additive effects for adaptive tracking performance,
      saccadic peak velocity, subjective alertness and, possibly, calmness, but not on
      body sway, smooth pursuit, VAS for alcohol intoxication, or memory testing. To
      conclude, administration of almorexant together with ethanol was associated with
      additive effects for some of the measured cognitive and psychomotor performance
      tests. No indications of synergistic effects of almorexant and ethanol for any
      measured variable were observed.

PMID- 22658403
TI  - [Scarred uterus: the right of patients on the mode of delivery].

PMID- 22658404
TI  - [Volvulus following barbed suture].
AB  - Some use barbed suture to accomplish peritoneal closure at the end of
      laparoscopic sacral colpopexy. We describe two new cases of bowel obstruction
      syndrome as adverse events of this technique.

PMID- 22658405
TI  - Communication when patients are conscious during respirator treatment--a
      hermeneutic observation study.
AB  - AIM: The aim of this study was to observe, interpret and describe nurses'
      communication with conscious patients receiving mechanical ventilation treatment
      (MVT) in an intensive care unit (ICU), and to examine if such communication could
      be interpreted as caring. DESIGN: Hermeneutic observational study inspired by the
      philosophy of Gadamer. METHOD: Nineteen patients were observed on several
      occasions for a total of 66 hours, when conscious during MVT. FINDINGS: A form of
      caring communication was identified and interpreted as comprising seven themes:
      being attentive and watchful, being inclusive and involving, being connected,
      remaining close, being reassuring and providing security, keeping company and
      using humour and using a friendly approach. Communication that mediated a non
      caring approach was also identified and described under two thematic headings,
      i.e. being neglectful and being absent. CONCLUSIONS: Caring is communicated by
      the caring act of "standing-by" the patient. Caring or non-caring is communicated
      in non-verbal and verbal communication, in the words used, the tone of voice and
      behaviour, as well as in the performance of nursing care activities.

PMID- 22658406
TI  - Introduction to advanced biologics.
AB  - The changing structure and environment of the animal industry have brought about
      the need for new-generation vaccines, therapeutic methods, and diagnostic
      methods. This review briefly explains the present situation and future prospects
      of advanced biologics.

PMID- 22658407
TI  - Oxidative stress and inflammation in hyperglycemic crises and resolution with
      insulin: implications for the acute and chronic complications of hyperglycemia.

PMID- 22658408
TI  - Geographic variation in pharmacotherapy decisions for U.S. Medicare enrollees
      with diabetes.
AB  - OBJECTIVES: Prescription rates for diabetic drugs vary considerably across the
      United States for Medicare beneficiaries. The goal of this study was to determine
      if non-clinical factors (patient race, ethnicity, gender, income) are associated
      with regional variation in pharmacotherapy decisions for diabetic patients
      enrolled in Medicare. METHODS: We performed a spatially-weighted, linear
      regression analysis of the entire diabetic population enrolled in Medicare Parts
      A, B, and D for the years 2006 through 2009. Our outcomes of interest were the
      percentage of diabetic patients being treated with metformin, a sulfonylurea, a
      thiazolidinedione, or insulin within a hospital referral region (HRR). RESULTS:
      Prescription rates for metformin, sulfonylureas, thiazolidinediones, and insulin
      varied more than two-fold between hospital referral region. Metformin
      prescription rates were increased in western states while prescription rates for
      sulfonylureas and insulins were highest in the South and Midwest. In contrast
      with these other diabetic drug classes, members of the thiazolidinedione drug
      class were prescribed more frequently in the Central United States (Great Plains,
      Colorado Rockies, Northern Texas, Oklahoma). Prescription rates for each drug
      class were increased in hospital referral regions with a lower household income.
      Referral regions with larger African American populations were associated with
      higher prescription rates for insulin (p<0.001) and lower prescription rates for
      metformin (p<0.001). Gender and Hispanic ethnicity were not associated with
      regional variation in prescription rates for the four major diabetic drug
      classes. CONCLUSIONS: Geographic differences exist in the management of type 2
      diabetes for Medicare enrollees. Prescription patterns were associated with
      household income and African American race. Further studies are necessary to
      identify local, unidentified factors that might be influencing provider
      management styles.

PMID- 22658409
TI  - The relationship between oxidative stress and the levels of serum circulating
      adhesion molecules in patients with hyperglycemia crises.
AB  - OBJECTIVE: To investigate the relationship between oxidative stress and the
      levels of serum circulating adhesion molecules in patients with hyperglycemia
      crises. METHODS: A total of 73 patients with diabetic ketoacidosis and nonketotic
      hyperglycemia were treated on a low-dose insulin protocol using intravenous
      infusion of insulin with the established rate of 0.1U.kg(-1).h(-1). The patients
      received intravenous fluids and nutrition orally and intravenously. The levels of
      serum ICAM-1, E-selectin, and 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha));
      the activities of superoxide dismutase (SOD); the total antioxidant capacity
      (TAC) and the contents of malondialdehyde (MDA) in 68 patients with hyperglycemia
      crisis on admission and after insulin therapy with resolution of hyperglycemia
      and ketoacidosis (72 h after resolution) were measured. Another 33 healthy
      individuals served as normal controls. RESULTS: The activities of SOD and TAC at
      admission were lower in patients with hyperglycemia crisis than in normal
      controls, and the levels of MDA, 8-iso-PGF(2alpha), ICAM-1 and E-selectin were
      higher in patients with hyperglycemia crisis than in normal controls (all
      p<0.05). The activities of SOD and TAC in patients at resolution were
      significantly lower than in patients at admission and were significantly higher
      than in controls (p<0.05). The levels of MDA, 8-iso-PGF(2alpha), ICAM-1 and E
      selectin in patients at resolution were markedly lower than in patients at
      admission (all p<0.05) and were significantly higher than in normal controls
      (p<0.05). There was a significant positive correlation between ICAM-1 and SOD
      (r=0.32, p<0.05) and between E-selectin and MDA (r=0.30, p<0.05) in patients at
      admission, and the level of E-selectin was positively correlated with MDA and 8
      iso-PGF(2alpha) in patients at resolution (r=0.33, 0.36, p<0.05). In stepwise
      regression analysis, MDA and 8-iso-PGF(2alpha) showed a significant association
      with E-selectin, and 8-iso-PGF(2alpha) showed a significant association with ICAM
      1. CONCLUSION: The oxidative stress and the levels of serum circulating adhesion
      molecules are significantly changed in patients with hyperglycemia crisis.
      Intensive insulin therapy can attenuate the abnormity of oxidative stress and the
      levels of serum circulating adhesion molecules in patients with hyperglycemia
      crisis.

PMID- 22658410
TI  - Deteriorating tactile sensation in patients with hand syndromes associated with
      diabetes: a two-year observational study.
AB  - AIMS: To observe the natural history of hand function during a two-year period in
      participants with hand syndromes associated with diabetes and to determine
      factors related to changing function. METHODS: Hand function was measured over
      three annual visits using Disability of the Arm, Shoulder and Hand (DASH) and SF
      36v2 questionnaires, grip strength, light touch and 9-hole peg tests. Light touch
      was tested with WEST monofilaments at 7 sites on the hand (score 35 to 0). Data
      were analyzed using repeated-measures ANOVA, Spearman's correlation, and Wilcoxon
      signed-rank tests. RESULTS: Participants (n=60) were aged 61 +/- 10.5 years, 57%
      female, diagnosed with diabetes and at least one of four associated hand
      disorders. Presentations of carpal tunnel syndrome, or past release (n=27, 45%)
      and trigger finger (n=24, 40%) were common. Tactile sensation was reduced during
      the two-year period (median, range; 30 months, 25-40 months). Initial median
      (inter-quartile range) scores for the dominant hand of 25.5 (22-28.5) were
      reduced to 23 (21.5-27). This sensory loss was weakly associated with HbA1c
      (r=0.30, p=0.05) and occurred predominantly in participants with trigger finger
      (p=0.05). CONCLUSIONS: Light touch perception was reduced in longstanding
      diabetic hand syndromes. Tactile abnormalities that were detected by clinical
      examination progressed during a two year period and were related to metabolic
      control and musculoskeletal diagnosis.

PMID- 22658412
TI  - [Non-AIDS defining malignancies, or the sleeping giant: an update].
AB  - Non-AIDS defining malignancies (NADM) are a very heterogeneous group of cancers
      with increasing importance in subjects with HIV infection. They develop in
      patients that are younger than general population and their clinical
      manifestations are usually atypical, with higher tumour grades, more aggressive
      clinical behaviour and metastatic disease. The outcome is poor, with rapid
      progression, a high rate of relapse, and a poor response to treatment. There are
      several factors that influence their development: HIV infection, chronic
      immunosuppression, and co-infection with some oncogenic viruses. The most
      frequent NADM are those associated with human papillomavirus infection, lung
      cancer, hepatic cancer, and Hodgkin lymphoma. Their management is based on three
      essential points: the treatment of the specific malignancy, the use of
      antiretroviral therapy, and the prophylaxis and treatment of opportunistic
      infections. The two factors significantly associated with prevention of NADM are
      a CD4+ lymphocyte count more than 500/mm(3), and an undetectable viral load.

PMID- 22658411
TI  - Prevention of VEGF-induced growth and tube formation in human retinal endothelial
      cells by aldose reductase inhibition.
AB  - OBJECTIVE: Since diabetes-induced vascular endothelial growth factor (VEGF) is
      implicated in retinal angiogenesis, we aimed to examine the role of aldose
      reductase (AR) in VEGF-induced human retinal endothelial cells (HREC) growth and
      tube formation. MATERIALS AND METHODS: HRECs were stimulated with VEGF and cell
      growth was determined by MTT assay. AR inhibitor, fidarestat, to block the enzyme
      activity and AR siRNA to ablate AR gene expression in HREC were used to
      investigate the role of AR in neovascularization using cell-migration and tube
      formation assays. Various signaling intermediates and angiogenesis markers were
      assessed by Western blot analysis. Immuno-histochemical analysis of diabetic rat
      eyes was performed to examine VEGF expression in the retinal layer. RESULTS:
      Stimulation of primary HREC with VEGF caused increased cell growth and migration,
      and AR inhibition with fidarestat or ablation with siRNA significantly prevented
      it. VEGF-induced tube formation in HREC was also significantly prevented by
      fidarestat. Treatment of HREC with VEGF also increased the expression of VCAM,
      AR, and phosphorylation and activation of Akt and p38-MAP kinase, which were
      prevented by fidarestat. VEGF-induced expression of VEGFRII in HREC was also
      prevented by AR inhibition or ablation. CONCLUSIONS: Our results indicate that
      inhibition of AR in HREC prevents tube formation by inhibiting the VEGF-induced
      activation of the Akt and p38-MAPK pathway and suggest a mediatory role of AR in
      ocular neovascularization generally implicated in retinopathy and AMD.

PMID- 22658413
TI  - Biases in children's and adults' moral judgments.
AB  - Two experiments examined biases in children's (5/6- and 7/8-year-olds) and
      adults' moral judgments. Participants at all ages judged that it was worse to
      produce harm when harm occurred (a) through action rather than inaction (omission
      bias), (b) when physical contact with the victim was involved (physical contact
      principle), and (c) when the harm was produced as a direct means to an end rather
      than as an unintended but foreseeable side effect of the action (intention
      principle). The youngest participants, however, did not incorporate benefit when
      making judgments about situations in which harm to one individual resulted in
      benefit to five individuals. Older participants showed some preference for
      benefit resulting from action (commission) as opposed to inaction (omission). The
      findings are discussed in the context of the theory that moral judgments result,
      in part, from the operation of an inherent, intuitive moral faculty compared with
      the theory that moral judgments require development of necessary cognitive
      abilities.

PMID- 22658414
TI  - Accuracy and safety of (99m)Tc-labeled anti-D-dimer (DI-80B3) Fab' fragments
      (ThromboView(r)) in the diagnosis of deep vein thrombosis: a phase II study.
AB  - BACKGROUND: The assessment of patients with suspected deep vein thrombosis (DVT)
      remains challenging despite current diagnostic algorithms. (99m)Tc-labelled DI
      DD3B6/22-80B3 Fab' fragments ((99m)Tc-DI-80B3, ThromboView(r)) is a novel
      diagnostic test that uses a radiolabelled humanized monoclonal antibody fragment
      specific for the D-dimer region of cross-linked fibrin to detect DVT. This test
      has an anatomic component to locate DVT and a functional component to
      differentiate acute (newly formed) thrombus from inactive (old) thrombus.
      METHODS: In a multi-centre prospective cohort trial we investigated the
      diagnostic accuracy and safety of (99m)Tc-DI-80B3 in consecutive patients with
      suspected DVT who had the diagnosis confirmed or excluded by venography. RESULTS:
      We enrolled 94 patients with suspected DVT of whom 12 did not have (99m)Tc-DI
      80B3 imaging, leaving 82 patients for the safety analysis. Of these patients,
      there were 16 with non-evaluable imaging (11 venography, 7 (99m)Tc-DI-80B3, both
      in two patients) leaving 66 patients for the accuracy analysis. (99m)Tc-DI-80B3
      imaging was well-tolerated: 2 patients developed urticaria; none developed
      serious adverse events. For proximal DVT, the sensitivity (84.2%; 95% confidence
      interval [CI]: 62.4-94.5) and specificity (97.6%; CI: 83.3-99.4) were highest
      when the combined 0.25-hour and 3-hour (99m)Tc-DI-80B3 images were used. The
      accuracy was lower for distal DVT, irrespective of the images used. There were
      insufficient patients to comment on the accuracy of (99m)Tc-DI-80B3 imaging for
      suspected recurrent DVT. CONCLUSIONS: (99m)Tc-DI-80B3 (ThromboView(r)) is a novel
      diagnostic modality for patients with suspected DVT with a promising accuracy and
      safety profile that justifies additional clinical development in diagnostic
      accuracy and clinical management studies.

PMID- 22658415
TI  - A direct HDAC4-MAP kinase crosstalk activates muscle atrophy program.
AB  - Prolonged deficits in neural input activate pathological muscle remodeling,
      leading to atrophy. In denervated muscle, activation of the atrophy program
      requires HDAC4, a potent repressor of the master muscle transcription factor
      MEF2. However, the signaling mechanism that connects HDAC4, a protein
      deacetylase, to the atrophy machinery remains unknown. Here, we identify the AP1
      transcription factor as a critical target of HDAC4 in neurogenic muscle atrophy.
      In denervated muscle, HDAC4 activates AP1-dependent transcription, whereas AP1
      inactivation recapitulates HDAC4 deficiency and blunts the muscle atrophy
      program. We show that HDAC4 activates AP1 independently of its canonical
      transcriptional repressor activity. Surprisingly, HDAC4 stimulates AP1 activity
      by activating the MAP kinase cascade. We present evidence that HDAC4 binds and
      promotes the deacetylation and activation of a key MAP3 kinase, MEKK2. Our
      findings establish an HDAC4-MAPK-AP1 signaling axis essential for neurogenic
      muscle atrophy and uncover a direct crosstalk between acetylation- and
      phosphorylation-dependent signaling cascades.

PMID- 22658416
TI  - Nascent-seq indicates widespread cotranscriptional RNA editing in Drosophila.
AB  - The RNA editing enzyme ADAR chemically modifies adenosine (A) to inosine (I),
      which is interpreted by the ribosome as a guanosine. Here we assess
      cotranscriptional A-to-I editing in Drosophila by isolating nascent RNA from
      adult fly heads and subjecting samples to high throughput sequencing. There are a
      large number of edited sites within nascent exons. Nascent RNA from an ADAR-null
      strain was also sequenced, indicating that almost all A-to-I events require ADAR.
      Moreover, mRNA editing levels correlate with editing levels within the cognate
      nascent RNA sequence, indicating that the extent of editing is set
      cotranscriptionally. Surprisingly, the nascent data also identify an excess of
      intronic over exonic editing sites. These intronic sites occur preferentially
      within introns that are poorly spliced cotranscriptionally, suggesting a link
      between editing and splicing. We conclude that ADAR-mediated editing is more
      widespread than previously indicated and largely occurs cotranscriptionally.

PMID- 22658417
TI  - Injuries associated with serious brachial plexus involvement in polytrauma among
      patients requiring surgical repair.
AB  - BACKGROUND: Brachial plexus injury occurs in up to 5% of polytrauma cases
      involving motorcycle crashes and in approximately 4% of severe winter sports
      injuries. One of the conditions for the success of operative therapy is early
      detection, ideally within three months of injury. The aim of this study was to
      evaluate associated injuries in patients with severe brachial plexus injury and
      determine whether there is a characteristic concomitant injury (or injuries), the
      presence of which, in the polytrauma, could act as a marker for nerve structures
      involvement and whether there are differences in severity of polytrauma
      accompanying specific types of brachial plexus injury. METHODS: We evaluated
      retrospectively 84 surgical patients from our department, from 2008 to 2011, that
      had undergone brachial plexus reconstruction. For all, an injury severity scale
      (ISS) score and all major associated injuries were determined. RESULTS: 72% of
      patients had an upper, 26% had a complete and only 2% had a lower brachial plexus
      palsy. The main cause was motorcycle crashes (60%) followed by car crashes (15%).
      The average ISS was 35.2 (SD=23.3), although, values were significantly higher in
      cases involving a coma (59.3, SD=11.0). The lower and complete plexus injuries
      were significantly associated with coma and fractures of the shoulder girdle and
      injuries of lower limbs, thoracic organs and head. Upper plexus injuries were
      associated with somewhat less severe injuries of the upper and lower extremities
      and less severe injuries of the spine. CONCLUSION: Serious brachial plexus injury
      is usually accompanied by other severe injuries. It occurs in high-energy trauma
      and it can be stated that patients involved in motorcycle and car crashes with
      multiple fractures of the shoulder girdle are at high risk of nerve trauma. This
      is especially true for patients in a primary coma. Lower and complete brachial
      plexus injuries are associated with higher injury severity scale.

PMID- 22658418
TI  - The temporal course of intracranial haemorrhage progression: how long is
      observation necessary?
AB  - INTRODUCTION: Patients with mild traumatic brain injury (MTBI) and intracranial
      haemorrhage (ICH) are hospitalized and monitored for progression of injury. The
      timeframe for ICH progression is unknown, and so the optimal duration and
      location of observation are generally discretionary. The goal of this study was
      to examine the temporal course of injury progression and establish a timeframe
      for when haemorrhage ceases. METHODS: We performed a retrospective review of all
      adult patients (age >= 18) with MTBI (GCS >= 13) and ICH admitted to a level 1
      trauma centre over a consecutive 36 month period, who underwent a minimum of 2
      cranial CT scans (HCT) within 48 h from ED presentation prior to any
      neurosurgical intervention (NSI). Patients with a history of NSI or nontraumatic
      cerebral lesions were excluded. Data collected include demographics and the
      number, timing and findings of serial HCT scans. RESULTS: A total of 341 patients
      met inclusion criteria. The timing for cessation of bleeding could not be
      confirmed in 37 patients (11 had NSI after 2nd HCT, 1 died of coagulopathy prior
      to NSI and 25 had no repeat HCT that could confirm the cessation of bleeding). Of
      the remaining 304 ICH, 96% stopped progressing by 24h and 99% by 48 h. The
      remaining 1% stopped by 72 h. Of all 341 ICH, 236 (69%) showed no progression
      after initial HCT, indicating that haemorrhage had stopped by that time (1.2h (SD
      +/- 1.1h) from admission). None required a NSI. CONCLUSION: Almost all ICH in
      MTBI stop progressing within the first 24h post injury, supporting a 24-h
      observational period. In fact, over 3/4s of ICH has stopped by the time of the
      initial HCT (<2h from arrival). This suggests that early repeat HCT may identify
      those ICH no longer progressing, and possibly avoid unnecessary admission and
      prolonged observation in those patients not requiring admission for post-TBI
      symptom management. Prospective data are needed to evaluate this proposed
      paradigm change in the management of MTBI.

PMID- 22658419
TI  - Perioperative glucocorticosteroid treatment delays early healing of a mandible
      wound by inhibiting osteogenic differentiation.
AB  - AIM: The purpose of this study is to investigate the effects of dexamethasone on
      repair of a critical size defect of the mandible in male Sprague-Dawley rats.
      MATERIALS AND METHODS: Fifty rats were divided into 2 groups: saline control and
      dexamethasone-treated groups. A 1 mm * 3 mm full-thickness bone defect was
      created at the inferior border of the mandible. Saline or dexamethasone was
      administered once a day for 5 days after postoperative palinesthesia. On days 1,
      3, 6, 10 and 17, after cessation of drug administration, 5 samples from each
      group were analysed. The bone defect healing process was examined and analysed by
      stereology, radiology, histology and histochemical staining for total collagen,
      tartrate-resistant acid phosphatase staining for osteoclasts and
      immunohistochemical staining for the COX-2, RUNX2 and osteocalcin antigens.
      RESULTS: The dexamethasone-treated rats exhibited significantly lower radiopacity
      properties compared to the control rats. Histological staining revealed that the
      osteogenic differentiation and maturation of a callus in the defect region was
      significantly delayed from day 1 to day 10 in the dexamethasone group after
      cessation of drug administration compared to the control group. Consistent with
      the histological data, the level of total collagen protein was significantly
      lower in the dexamethasone group than in the control group. However, there was no
      significant difference between the 2 groups at day 17. Immunohistochemical
      analysis of COX-2, RUNX2 and osteocalcin expression showed that, at day 1, COX-2
      and RUNX2 expression in the dexamethasone group was significantly lower than in
      the control group. There was no significant difference in osteocalcin expression
      between the two groups at each time point. There was no significant difference in
      the number of osteoclasts between the two groups. CONCLUSION: In a model of bone
      healing of a mandible defect, dexamethasone-treated rats exhibited impaired
      osteogenic differentiation and maturation due to the inhibition of COX-2,
      osteogenic gene, RUNX2 and collagen protein expression, which resulted in delayed
      bone repair. Although perioperative short-term therapy did not exhibit long-term
      effects on wound healing of the maxillofacial bone, the application of
      glucocorticoids should be cautiously considered in the clinic.

PMID- 22658420
TI  - Catastrophic household costs due to injury in Vietnam.
AB  - OBJECTIVE: Little is known about the costs of injury and their impact on injured
      persons and their families in Vietnam. This study aimed to examine the cost of
      injury in hospitalised patients and to identify the most costly injuries and
      those more likely to result in catastrophic household expenditure. METHOD: A
      prospective cohort study was conducted, recruiting individuals admitted to Thai
      Binh General Hospital due to injury in Vietnam from January to August 2010.
      During the hospitalisation period, data on expenditure including direct medical,
      direct non-medical and indirect costs were collected. Demographic and injury
      characteristics were also obtained. The associations between the risk of
      catastrophic expenditure and injury cause, severity and principal injured region
      were examined by modified Poisson regression approach. Payment of more than 40%
      of the household non-subsistence spending was considered a catastrophic
      expenditure. RESULTS: Of 918 patients approached, 892 (97%) were recruited. Total
      costs for all participants during the hospitalisation period were US$ 325,812.
      Patients admitted for road injury accounted for the largest number of injuries
      (n=477, 53%), and the largest percentage of the total costs (US$ 175,044, 57%).
      This was followed by individuals hospitalised due to falls, representing 29% of
      the sample (n=261) and 31% of the total costs (US$ 103,128). In terms of cost per
      hospital stay, burn injuries were the most costly (US$ 427), followed by falls
      (US$ 395) and road crashes (US$ 367). Of all sample, 26% experienced catastrophic
      expenditure due to their injuries. Factors significantly associated with
      increased risk of catastrophic expenditure were having more severe or higher MAIS
      injuries (RR=2.02, 95% CI: 1.14-3.57), principal injured region to lower
      extremities (RR=3.34, 95% CI: 1.41-7.91) or head (RR=3.21, 95% CI: 1.37-7.52),
      longer hospital stay (RR=1.09, 95% CI: 1.07-1.10), older age, lower income and
      not having insurance (RR=1.63, 95% CI: 1.21-2.21). CONCLUSION: A high proportion
      of households experienced catastrophic expenditure following injury, highlighting
      the important need for programmes to prevent injuries, road traffic and fall
      related injuries in particular. Furthermore, expansion of health insurance
      coverage may help individuals cope with the financial consequences of injury.

PMID- 22658421
TI  - ATLS adherence in the transfer of rural trauma patients to a level I facility.
AB  - BACKGROUND: Injury sustained in rural areas has been shown to carry higher
      mortality rates than trauma in urban settings. This disparity is partially
      attributed to increased distance from definitive care and underscores the
      importance of proper primary trauma management prior to transfer to a trauma
      facility. The purpose of this study was to assess Advanced Trauma Life Support
      (ATLS) guideline adherence in the management of adult trauma patients transferred
      from rural hospitals to a level I facility. METHODS: We performed a retrospective
      analysis of all adult major trauma patients transferred >=50km from an outlying
      hospital to a level I trauma centre from 2007 through 2009. Transfer practices
      were evaluated using ATLS guidelines. RESULTS: 646 patients were analyzed. Mean
      age was 40.5years and 94% sustained blunt injuries with a median Injury Severity
      Score (ISS) of 22. Median transport distance was 253km. Among all patients, there
      were notable deficiencies (<80% adherence) in 8 of 11 ATLS recommended
      interventions, including patient rewarming (8% adherence), chest tube insertion
      (53%), adequate IV access (53%), and motor/sensory exam (72%). Patients with
      higher ISS scores, and those transferred by air were more likely to receive ATLS
      recommended interventions. CONCLUSIONS: Key aspects of ATLS resuscitation
      guidelines are frequently missed during transfer of trauma patients from the
      periphery to level I trauma centres. Comprehensive quality improvement
      initiatives, including targeted education, telemedicine and trauma team training
      programmes could improve quality of care.

PMID- 22658422
TI  - Differential effects of dobutamine versus treadmill exercise on left ventricular
      volume and wall stress.
AB  - BACKGROUND: Dobutamine and exercise echocardiography are well-validated
      modalities used for the evaluation of patients with suspected myocardial
      ischemia. Patients undergoing dobutamine stress echocardiography (DSE), however,
      experience less angina, ST-segment depressions, and wall motion abnormalities.
      Other than the effect on heart rate, the physiologic and volumetric differences
      between pharmacologic and exercise-induced stress that affect myocardial oxygen
      demand are not well defined. The aim of this study was to test the hypothesis
      that in the absence of ischemia, dobutamine reduces left ventricular (LV) volume,
      wall tension (WTN), and peak systolic stress (PSS) compared with exercise.
      METHODS: Seventy patients without ischemia were prospectively enrolled (35
      underwent exercise echocardiography and 35 DSE), and various hemodynamic
      parameters were measured and LV volumes calculated (using the Simpson and
      Teichholz formulas). Systolic WTN and PSS were determined at rest and stress.
      RESULTS: LV end-diastolic volume index fell significantly more with dobutamine
      than with exercise (-34% vs -9%, P < .0001), as did mean end-systolic volume
      index (-55% vs -37%, P = .07). Systolic blood pressure increased more with
      exercise (41 +/- 22 vs 1 +/- 33 mm Hg, P < .0001), as did cardiac index (2.5 +/-
      0.7 vs 1.0 +/- 0.8 L/min/m(2), P < .0001). Systolic WTN increased with exercise
      by 24% (P < .0001) but decreased with dobutamine by 18% (P < .0001). PSS
      increased with exercise by 21% (P < .0001) but decreased with dobutamine by 23%
      (P < .0001). CONCLUSIONS: The degree of stress achieved with DSE appears to be
      considerably different than with exercise. DSE produces greater reductions in LV
      end-diastolic and end-systolic volumes than exercise and decreases rather than
      increases in WTN and PSS. The lower WTN and PSS were related to both a decrease
      in LV volume and lower systolic blood pressure with dobutamine. These
      observations support recommendations favoring exercise stress testing in patients
      able to exercise and reinforce the notion that high-risk echocardiographic
      features of ischemia such as stress-induced LV dilatation may be less striking or
      absent with DSE.

PMID- 22658423
TI  - Three-dimensional speckle-tracking analysis of left ventricular function after
      transcatheter aortic valve implantation.
AB  - BACKGROUND: The acute and long-term effects of transcatheter aortic valve
      implantation (TAVI) in patients with aortic valve stenosis on left ventricular
      (LV) function are controversial. The aim of this study was to determine the
      effect of TAVI on LV function with two-dimensional (2D) and three-dimensional
      (3D) speckle-tracking analysis of LV deformation capability. METHODS: Patients
      underwent standardized 2D and 3D transthoracic echocardiography before TAVI and
      after 6 months of follow-up, including 3D and 2D LV deformation imaging. RESULTS:
      Forty-four patients (mean age, 81.7 +/- 5.5 years; 21 men [47.7%]; mean body mass
      index, 26.3 +/- 5.1 kg/m(2); mean logistic European System for Cardiac Operative
      Risk Evaluation score, 24.4 +/- 13.7%) undergoing TAVI were prospectively
      included. After follow-up, mean 3D LV ejection fraction (LVEF) (35.4 +/- 13.1% vs
      40.6 +/- 12.6%, P = .004), 3D LV volumes (end-systolic volume, 85.9 +/- 41.8 vs
      65.9 +/- 33.7 mL, P < .001; end-diastolic volume, 127.6 +/- 40.7 vs 106.4 +/-
      40.9 mL, P = .001), 3D global longitudinal strain (-9.9 +/- 3.7% vs -12.6 +/-
      4.2%, P < .001), and 3D LV twist (6.1 +/- 4.3 degrees  vs 8.5 +/- 6.9 degrees , P
      = .025) were relevantly improved. LV improvement was pronounced in patients with
      decreased baseline LV function (area under the curve, 0.78; P < .001), with a
      cutoff value for 3D LVEF of <=37% to identify functional responders to TAVI.
      After follow-up, patients with 3D LVEFs <= 37% showed a significant improvements
      in 3D LVEF (26.0 +/- 7.6% vs 35.9 +/- 11.7%, P < .001), 3D LV volumes (end
      diastolic volume, 147.4 +/- 40.6 vs 117.1 +/- 45.5 mL, P = .001; end-systolic
      volume, 110.9 +/- 39.2 vs 77.5 +/- 37.2 mL, P < .001), 3D global longitudinal
      strain (-7.8 +/- 2.7% vs -11.3 +/- 4.2%, P < .001), and 3D LV twist (5.6 +/- 4.2
      degrees  vs 8.0 +/- 5.6 degrees , P = .047), whereas in patients with 3D LVEFs >
      37%, only 3D global longitudinal strain was relevantly altered (-12.5 +/- 3.1% vs
      -14.2 +/- 3.8%, P = .04). Compared with 2D transthoracic echocardiography, 3D LV
      functional imaging allowed significantly faster image acquisition and data
      analysis (P < .0001). New York Heart Association functional class improved
      significantly in both groups (3D LVEF <= 37%, from 3.1 +/- 0.5 to 2.0 +/- 0.6, P
      < .001; 3D LVEF > 37%, from 2.7 +/- 6.7 to 1.5 +/- 0.7, P < .001), whereas a
      significant amelioration of N-terminal pro-brain natriuretic peptide was observed
      only in patients with baseline 3D LVEFs <= 37% (10,314.64 +/- 11,682.2 vs 3,398.7
      +/- 3,598.9 pg/mL, P = .02; 3D LVEF > 37%, 10,306.4 +/- 32,000.5 vs 2,868.0 +/-
      3,816.7 pg/mL, P = .12). CONCLUSIONS: Our results indicate significant
      improvements of LV global and longitudinal function and clinical parameters 6
      months after TAVI that are pronounced in patients with impaired baseline LV
      function. Compared with 2D LV functional imaging, 3D speckle-tracking imaging
      allowed significantly faster image acquisition and data analysis.

PMID- 22658424
TI  - Regional ventilation in cystic fibrosis measured by electrical impedance
      tomography.
AB  - BACKGROUND: The feasibility of electrical impedance tomography (EIT) as an
      alternative examination tool in cystic fibrosis (CF) was examined. METHODS: 14 CF
      patients and 14 healthy volunteers were studied. Spirometry and EIT measurements
      were performed simultaneously. The global inhomogeneity (GI) index was applied to
      assess the degree of ventilation homogeneity at different levels of maximum
      inspiratory volume. Ratios of maximum expiratory flow at 25% and 75% of vital
      capacity (MEF(25)/MEF(75)) were calculated for both global lung and regional
      areas in EIT images. RESULTS: Significant differences among GI values at various
      lung volumes were found in CF patients (P<0.01) but not in healthy subjects.
      Global MEF(25)/MEF(75) measured with spirometry and with EIT were highly
      correlated for all subjects (r(2)=0.69, P<0.01). Significant difference in global
      MEF(25)/MEF(75) was found between CF patients and healthy volunteers with both
      spirometer (CF: 0.15+/-0.09; healthy: 0.46+/-0.15; P<0.001) and EIT (CF: 0.14+/
      0.09; healthy: 0.42+/-0.08; P<0.001). Regional airway obstruction was identified
      in the MEF(25)/MEF(75) maps in CF patients. CONCLUSIONS: Compared to the global
      parameters provided by spirometry, EIT is able to deliver both global and
      regional information to assess the airway obstruction in CF patients.

PMID- 22658425
TI  - Child maltreatment.
AB  - Oral and maxillofacial surgeons are in a unique position to identify and report
      child abuse. In the career of any practitioner, maltreated children (both
      physically abused and neglected) will present for management of injuries and
      infections. There must be a high level of vigilance for, and understanding of,
      mechanisms of injury and skill in sorting out inflicted injuries or evidence of
      neglect. Because of this, the medical community, society, state law, and the
      legal system place oral and maxillofacial surgeons in a position of expertise and
      accountability in the care of children.

PMID- 22658426
TI  - A novel method for simultaneous Enterococcus species identification/typing and
      van genotyping by high resolution melt analysis.
AB  - In order to develop a typing and identification method for van gene containing
      Enterococcus faecium, two multiplex PCR reactions were developed for use in HRM
      PCR (High Resolution Melt-PCR): (i) vanA, vanB, vanC, vanC23 to detect van genes
      from different Enterococcus species; (ii) ISR (intergenic spacer region between
      the 16S and 23S rRNA genes) to detect all Enterococcus species and obtain species
      and isolate specific HRM curves. To test and validate the method three groups of
      isolates were tested: (i) 1672 Enterococcus species isolates from January 2009 to
      December 2009; (ii) 71 isolates previously identified and typed by PFGE (pulsed
      field gel electrophoresis) and MLST (multi-locus sequence typing); and (iii) 18
      of the isolates from (i) for which ISR sequencing was done. As well as
      successfully identifying 2 common genotypes by HRM from the Austin Hospital
      clinical isolates, this study analysed the sequences of all the vanB genes
      deposited in GenBank and developed a numerical classification scheme for the
      standardised naming of these vanB genotypes. The identification of Enterococcus
      faecalis from E. faecium was reliable and stable using ISR PCR. The typing of E.
      faecium by ISR PCR: (i) detected two variable peaks corresponding to different
      copy numbers of insertion sequences I and II corresponding to peak I and II
      respectively; (ii) produced 7 melt profiles for E. faecium with variable copy
      numbers of sequences I and II; (iii) demonstrated stability and instability of
      peak heights with equal frequency within the patient sample (36.4+/-4.5 days and
      38.6+/-5.8 days respectively for 192 patients); (iv) detected ISR-HRM types with
      as much discrimination as PFGE and more than MLST; and (v) detected ISR-HRM types
      that differentiated some isolates that were identical by PFGE and MLST. In
      conjunction with the rapid and accurate van genotyping method described here,
      this ISR-HRM typing and identification method can be used as a stable
      identification and typing method with predictable instability based on
      recombination and concerted evolution of the rrn operon that will complement
      existing typing methods.

PMID- 22658427
TI  - Effect of pre-incubation conditions on growth and survival of Staphylococcus
      aureus in sliced cooked chicken breast.
AB  - In this work, the effect of pre-incubation conditions (temperature: 10, 15, 37 
      degrees C; pH 5.5, 6.5 and water activity, a(w): 0.997, 0.960) was evaluated on
      the subsequent growth, survival and enterotoxin production (SE) of Staphylococcus
      aureus in cooked chicken breast incubated at 10 and 20  degrees C. Results showed
      the ability of S. aureus to survive at 10  degrees C when pre-incubated at low
      a(w) (0.960) what could constitute a food risk if osmotic stressed cells of S.
      aureus which form biofilms survive on dried surfaces, and they are transferred to
      cooked meat products by cross-contamination. Regarding growth at 20  degrees C,
      cells pre-incubated at pH 5.5 and a(w) 0.960 had a longer lag phase and a slower
      maximum growth rate. On the contrary, it was highlighted that pre-incubation at
      optimal conditions (37  degrees C/pH 6.5/a(w) 0.997) produced a better adaptation
      and a faster growth in meat products what would lead to a higher SE production.
      These findings can support the adoption of management strategies and preventive
      measures in food industries leading to avoid growth and SE production in meat
      products.

PMID- 22658428
TI  - Modular femoral neck fracture after primary total hip arthroplasty.
AB  - The use of modular femoral stems in primary total hip arthroplasty has increased
      considerably in recent years. These modular components offer the surgeon the
      ability to independently alter version, offset, and length of the femoral
      component of a hip arthroplasty. This increases the surgeon's ability to
      accurately recreate the relevant anatomy but increases the possibilities of
      corrosion and fracture. Multiple case reports have highlighted fractures of these
      modular components. We present a case of a fracture of a modular design that has
      had no previously reported modular neck fractures. The patient was informed that
      data concerning the case would be submitted, and he consented.

PMID- 22658429
TI  - A new technique for measuring wear in total hip arthroplasty using computed
      tomography.
AB  - Accurately estimating polyethylene wear in 3 dimensions, without the need for
      additional procedures or equipment, is of significant interest. We investigated
      the use of a high-resolution clinical computed tomographic (CT) scanner to
      estimate femoral head displacement relative to the cup as an indirect method of
      estimating polyethylene wear. A hip phantom was used to simulate the 3
      dimensional displacement of a femoral head. The phantom was imaged in a high
      resolution CT scanner. The mean difference between the true phantom displacement
      as positioned by micrometers and the calculated displacement based on the CT
      images was as follows: for the x-axis, 0 mm (SD, 0.213; SE, 0.058); y-axis, 0.039
      mm (SD, 0.035; SE, 0.026); and z-axis, 0.039 mm (SD, 0.051; SE, 0.020).

PMID- 22658430
TI  - National trends in primary total hip arthroplasty in extremely young patients: a
      focus on bearing surface usage.
AB  - The purpose of this study was to present national trends in primary total hip
      arthroplasty (THA) and bearing surface usage for patients 30 years and younger.
      Using the Healthcare-Cost-and-Utilization-Project Nationwide Inpatient Sample for
      the years 2006 to 2009, 8919 primary THA discharges (4454 coded by bearing
      surface) were identified in patients 30 years and younger. The most commonly used
      bearing surface was metal-on-metal (MoM), representing 37.6% of cases, followed
      by ceramic-on-ceramic (CoC) (24.6%), metal-on-polyethylene (MoP) (22.1%) and
      ceramic-on-polyethylene (15.7%). From 2006 to 2009, the percentage of THAs that
      used hard-on-hard bearing surfaces decreased (MoM: 42.9%-29.4%; CoC: 34.0%
      19.7%).This decrease in hard-on-hard bearing surface usage presents a challenge
      for surgeons treating young patients to find other acceptable durable bearings
      that do not have the potential problems associated with MoM or CoC.

PMID- 22658431
TI  - Acceptance of epilepsy surgery among adults with epilepsy--what do patients
      think?
AB  - Physician inertia is usually blamed for the underutilization of epilepsy surgery
      (ES) at the cost of increased patient disability and risk of mortality.
      Investigations on selected groups of patients with intractable TLE and minorities
      suggested that patient beliefs may also limit access to ES. To assess acceptance
      of ES among "mainstream" patients, we distributed an ad hoc questionnaire to 228
      adults attending epilepsy clinics and found widespread fears and misconceptions
      leading to unfavorable perception of ES, irrespective of diagnosis, seizure type,
      and degree of intractability. Moreover, while a group firmly rejected ES, the
      majority became more favorable when given further information about modality,
      rationale, and expected outcome of ES. Attitude changes correlated with patient's
      social profile. Neurologists are responsible for providing all pertinent
      information to potential surgical candidates as soon as indicated. Therefore, an
      untimely or inadequate intervention of the treating physician constitutes an
      additional barrier to optimal utilization of ES.

PMID- 22658432
TI  - The effect of topiramate plasma concentration on linguistic behavior, verbal
      recall and working memory.
AB  - This is the first study of the effect of topiramate on linguistic behavior and
      verbal recall using a computational linguistics system for automated language and
      speech analysis to detect and quantify drug-induced changes in speech recorded
      during discourse-level tasks. Healthy volunteers were administered a single, 100
      mg oral dose of topiramate in two double-blind, randomized, placebo-controlled,
      crossover studies. Subjects' topiramate plasma levels ranged from 0.23 to 2.81
      MUg/mL. We found a significant association between topiramate levels and
      impairment on measures of verbal fluency elicited during a picture description
      task, correct number of words recalled on a paragraph recall test, and reaction
      time recorded during a working memory task. Using the tools of clinical
      pharmacology and computational linguistics, we elucidated the relationship
      between the determinants of a drug's disposition as reflected in plasma
      concentrations and their impact on cognitive functioning as reflected in spoken
      language discourse.

PMID- 22658433
TI  - Validation of the Subjective Handicap of Epilepsy (SHE) in Brazilian patients
      with epilepsy.
AB  - The objectives of the study were to translate and adapt the Subjective Handicap
      of Epilepsy (SHE) instrument to Brazilian Portuguese and to determine its
      psychometric properties for the evaluation of quality of life in patients with
      epilepsy. A sample of 448 adult patients with epilepsy with different clinical
      profiles (investigation, preoperative period, postoperative period, and drug
      treatment follow-up) was evaluated with the SHE and the Epilepsy Surgery
      Inventory (ESI-55). Exploratory factorial analysis demonstrated that four factors
      explained 60.47% of the variance and were sensitive to discriminate the different
      clinical groups, with the preoperative group having the poorest quality of life.
      Internal consistency ranged from 0.92 to 0.96, and concurrent validity with the
      ESI-55 was moderate/strong (0.32-0.70). Test-retest reliability was confirmed,
      with an ICC value of 0.54 (2 days), 0.91 (7 days), and 0.97 (30 days). The SHE
      had satisfactory psychometric qualities for use in the Brazilian population,
      similar to those of the original version. The instrument seems to be more
      adequate in psychometric terms for the postoperative and drug treatment follow-up
      groups, and its use should be encouraged.

PMID- 22658434
TI  - Epilepsy and brain function: common ideas of Hughlings-Jackson and Wilder
      Penfield.
AB  - From studies of epilepsy, Hughlings-Jackson proposed a model of brain function
      including levels of consciousness, a hierarchy of nervous centers, and a sensory
      motor relationship. Hughlings-Jackson's ideas influenced Wilder Penfield, a
      pioneer of electrical stimulation for mapping of the human cerebral cortex. From
      his work with electrocortical stimulation in patients with epilepsy, Penfield
      observed what he referred to as a "record of the stream of consciousness,"
      similar to Hughlings-Jackson's "subject consciousness." Penfield expanded upon
      Hughlings-Jackson's work and suggested that although higher and lower centers
      explained reflex movements, another separate unaccounted for force controlled
      voluntary movements. These two functional units he termed the "computer (or
      automatic sensory-motor mechanism)" and the "mind's mechanism (or highest brain
      mechanism)." The ideas of John Hughlings-Jackson and Wilder Penfield represent a
      continuum of thought about the relationship of epilepsy and brain function and
      continue to be relevant to our current understanding of memory function and the
      mind-brain relationship.

PMID- 22658435
TI  - B-vitamin deficiency in patients treated with antiepileptic drugs.
AB  - Enzyme-inducing antiepileptic drugs (AEDs) produce many alterations in
      metabolism, including vitamin levels. Whether they produce clinically relevant
      deficiency of B vitamins has rarely been assessed. We obtained B-vitamin levels
      in patients who were being converted from an inducing AED (phenytoin or
      carbamazepine) to a non-inducing AED (levetiracetam, lamotrigine, or topiramate),
      with measurements both before and >= 6 weeks after the switch. A group of normal
      subjects underwent the same studies. Neither folate nor B12 deficiency was seen
      in any patient. Vitamin B6 deficiency was found in 16/33 patients (48%) taking
      inducers, compared to 1/11 controls (9%; p=0.031). After switch to non-inducers,
      only 7 patients (21%) were B6 deficient (p=0.027). The incidence of deficiency
      was similar regardless of which inducing or non-inducing AED was being taken. Our
      findings demonstrate that treatment with inducing AEDs commonly causes pyridoxine
      deficiency, often severe. This could conceivably contribute to the polyneuropathy
      sometimes attributed to older AEDs, as well as other chronic heath difficulties.

PMID- 22658436
TI  - Early-onset epilepsy as the main neurological manifestation of cerebrotendinous
      xanthomatosis.
AB  - Cerebrotendinous xanthomatosis (CTX) is a rare inherited metabolic disorder,
      which usually presents with diverse systemic manifestations (ophthalmologic,
      cardiac, and dermatologic symptoms), and neurological dysfunction, such as
      neuropsychiatric symptoms, cognitive decline, and ataxia. Epilepsy is rarely seen
      as the main neurological manifestation of CTX. Herein, we describe a middle-aged
      woman with epilepsy since childhood as the only neurological symptom associated
      with the classical systemic manifestations of CTX.

PMID- 22658437
TI  - Bright light therapy as an add on treatment for medically intractable epilepsy.
AB  - BACKGROUND: Bright light therapy (BLT) influences the regulation of melatonin and
      is an established treatment for seasonal affective disorder (SAD). This study was
      designed to examine the efficacy of BLT for seizure control in adults with focal
      epilepsy. DESIGN: 101 adults with medically intractable focal epilepsy were
      recruited to a parallel-design, double-blind, randomized trial of BLT as an add
      on treatment for epilepsy. METHODS: All patients monitored their seizure
      frequency at home for a 12-week baseline period (September 2010 to December
      2010). 51 of the participants were allocated with a high-intensity (HI) light box
      emitting 10,000 lx using an automated permuted block randomization grid. 50 were
      allocated with a cosmetically identical box emitting 2000 lx (low-intensity -
      LI), a subtherapeutic dose in other patient populations. Both groups were
      instructed to use their box for 20-30 min, upon waking every day for 12 weeks
      (January-March 2011). The primary outcome measure for the trial was seizure
      frequency. RESULTS: 77 participants (39 high-intensity/38 low-intensity)
      completed the trial and returned adequate data for analyses. Median reduction of
      seizures during the treatment phase was 1.5 in the LI group and 3 in the HI group
      (p>0.05). 6 patients (15%) in the high-intensity condition experienced an overall
      reduction of 50% or more in the frequency of complex partial seizures compared to
      9 (24%) patients who used the low intensity light box. Response rates in the HI
      and LI treatment conditions were not significantly different (p>0.05). Patients
      with hippocampal sclerosis were more likely to respond to BLT at either intensity
      than patients with other focal epilepsies (risk ratio=1.7 95% CI lower limit=0.6,
      upper limit=4.6). CONCLUSIONS: We did not find a significant difference in the
      responder rates in the low- vs. high-intensity arms of the trial. Some patterns
      within the data suggest that BLT may warrant further investigation as a treatment
      for people with hippocampal pathology. Our initial findings suggest that caution
      should be exercised in using BLT in people with extra temporal focal epilepsy as
      it may result in an increase in seizures for some.

PMID- 22658438
TI  - Acute radiation-induced nocturia in prostate cancer patients is associated with
      pretreatment symptoms, radical prostatectomy, and genetic markers in the TGFbeta1
      gene.
AB  - PURPOSE: After radiation therapy for prostate cancer, approximately 50% of the
      patients experience acute genitourinary symptoms, mostly nocturia. This may be
      highly bothersome with a major impact on the patient's quality of life. In the
      past, nocturia is seldom reported as a single, physiologically distinct endpoint,
      and little is known about its etiology. It is assumed that in addition to dose
      volume parameters and patient- and therapy-related factors, a genetic component
      contributes to the development of radiation-induced damage. In this study, we
      investigated the association among dosimetric, clinical, and TGFbeta1
      polymorphisms and the development of acute radiation-induced nocturia in prostate
      cancer patients. METHODS AND MATERIALS: Data were available for 322 prostate
      cancer patients treated with primary or postoperative intensity modulated
      radiation therapy (IMRT). Five genetic markers in the TGFbeta1 gene (-800 G>A, 
      509 C>T, codon 10 T>C, codon 25 G>C, g.10780 T>G), and a high number of clinical
      and dosimetric parameters were considered. Toxicity was scored using an symptom
      scale developed in-house. RESULTS: Radical prostatectomy (P<.001) and the
      presence of pretreatment nocturia (P<.001) are significantly associated with the
      occurrence of radiation-induced acute toxicity. The -509 CT/TT (P=.010) and codon
      10 TC/CC (P=.005) genotypes are significantly associated with an increased risk
      for radiation-induced acute nocturia. CONCLUSIONS: Radical prostatectomy, the
      presence of pretreatment nocturia symptoms, and the variant alleles of TGFbeta1 
      509 C>T and codon 10 T>C are identified as factors involved in the development of
      acute radiation-induced nocturia. These findings may contribute to the research
      on prediction of late nocturia after IMRT for prostate cancer.

PMID- 22658439
TI  - Estimation of the optimal brachytherapy utilization rate in the treatment of
      gynecological cancers and comparison with patterns of care.
AB  - PURPOSE: We aimed to estimate the optimal proportion of all gynecological cancers
      that should be treated with brachytherapy (BT)-the optimal brachytherapy
      utilization rate (BTU)-to compare this with actual gynecological BTU and to
      assess the effects of nonmedical factors on access to BT. METHODS AND MATERIALS:
      The previously constructed inter/multinational guideline-based peer-reviewed
      models of optimal BTU for cancers of the uterine cervix, uterine corpus, and
      vagina were combined to estimate optimal BTU for all gynecological cancers. The
      robustness of the model was tested by univariate and multivariate sensitivity
      analyses. The resulting model was applied to New South Wales (NSW), the United
      States, and Western Europe. Actual BTU was determined for NSW by a retrospective
      patterns-of-care study of BT; for Western Europe from published reports; and for
      the United States from Surveillance, Epidemiology, and End Results data.
      Differences between optimal and actual BTU were assessed. The effect of
      nonmedical factors on access to BT in NSW were analyzed. RESULTS: Gynecological
      BTU was as follows: NSW 28% optimal (95% confidence interval [CI] 26%-33%)
      compared with 14% actual; United States 30% optimal (95% CI 26%-34%) and 10%
      actual; and Western Europe 27% optimal (95% CI 25%-32%) and 16% actual. On
      multivariate analysis, NSW patients were more likely to undergo gynecological BT
      if residing in Area Health Service equipped with BT (odds ratio 1.76, P=.008) and
      if residing in socioeconomically disadvantaged postcodes (odds ratio 1.12,
      P=.05), but remoteness of residence was not significant. CONCLUSIONS:
      Gynecological BT is underutilized in NSW, Western Europe, and the United States
      given evidence-based guidelines. Access to BT equipment in NSW was significantly
      associated with higher utilization rates. Causes of underutilization elsewhere
      were undetermined. Our model of optimal BTU can be used as a quality assurance
      tool, providing an evidence-based benchmark against which actual patterns of
      practice can be measured. It can also be used to assist in determining the
      adequacy of BT resource allocation.

PMID- 22658440
TI  - Dosimetric benefit of a new ophthalmic radiation plaque.
AB  - PURPOSE: To determine whether the computed dosimetry of a new ophthalmic plaque,
      EP917, when compared with the standard Collaborative Ocular Melanoma Study (COMS)
      plaques, could reduce radiation exposure to vision critical structures of the
      eye. METHODS AND MATERIALS: One hundred consecutive patients with uveal melanoma
      treated with COMS radiation plaques between 2007 and 2010 were included in this
      study. These treatment plans were generated with the use of Bebig Plaque
      Simulator treatment-planning software, both for COMS plaques and for EP917
      plaques using I-125. Dose distributions were calculated for a prescription of 85
      Gy to the tumor apex. Doses to the optic disc, opposite retina, lens, and macula
      were obtained, and differences between the 2 groups were analyzed by standard
      parametric methods. RESULTS: When compared with the COMS plaques, the EP917
      plaques used fewer radiation seeds by an average difference of 1.94 (P<.001; 95%
      confidence interval [CI], -2.8 to -1.06) and required less total strength of
      radiation sources by an average of 17.74 U (air kerma units) (P<.001; 95% CI, 
      20.16 to -15.32). The total radiation doses delivered to the optic disc, opposite
      retina, and macula were significantly less by 4.57 Gy, 0.50 Gy, and 11.18 Gy,
      respectively, with the EP917 plaques vs the COMS plaques. CONCLUSION: EP917
      plaques deliver less overall radiation exposure to critical vision structures
      than COMS treatment plaques while still delivering the same total therapeutic
      dose to the tumor.

PMID- 22658441
TI  - A prospective, multicenter study of complementary/alternative medicine (CAM)
      utilization during definitive radiation for breast cancer.
AB  - PURPOSE: Although complementary and alternative medicine (CAM) utilization in
      breast cancer patients is reported to be high, there are few data on CAM
      practices in breast patients specifically during radiation. This prospective,
      multi-institutional study was conducted to define CAM utilization in breast
      cancer during definitive radiation. MATERIALS/METHODS: A validated CAM instrument
      with a self-skin assessment was administered to 360 Stage 0-III breast cancer
      patients from 5 centers during the last week of radiation. All data were analyzed
      to detect significant differences between users/nonusers. RESULTS: CAM usage was
      reported in 54% of the study cohort (n=194/360). Of CAM users, 71% reported
      activity-based CAM (eg, Reiki, meditation), 26% topical CAM, and 45% oral CAM.
      Only 16% received advice/counseling from naturopathic/homeopathic/medical
      professionals before initiating CAM. CAM use significantly correlated with higher
      education level (P<.001), inversely correlated with concomitant hormone/radiation
      therapy use (P=.010), with a trend toward greater use in younger patients
      (P=.066). On multivariate analysis, level of education (OR: 6.821, 95% CI: 2.307
      20.168, P<.001) and hormones/radiation therapy (OR: 0.573, 95% CI: 0.347-0.949,
      P=.031) independently predicted for CAM use. Significantly lower skin toxicity
      scores were reported in CAM users vs nonusers, respectively (mild: 34% vs 25%,
      severe: 17% vs 29%, P=.017). CONCLUSION: This is the first prospective study to
      assess CAM practices in breast patients during radiation, with definition of
      these practices as the first step for future investigation of CAM/radiation
      interactions. These results should alert radiation oncologists that a large
      percentage of breast cancer patients use CAM during radiation without disclosure
      or consideration for potential interactions, and should encourage increased
      awareness, communication, and documentation of CAM practices in patients
      undergoing radiation treatment for breast cancer.

PMID- 22658442
TI  - Brachial plexopathy in apical non-small cell lung cancer treated with definitive
      radiation: dosimetric analysis and clinical implications.
AB  - PURPOSE: Data are limited on the clinical significance of brachial plexopathy in
      patients with apical non-small cell lung cancers (NSCLC) treated with definitive
      radiation therapy. We report the rates of radiation-induced brachial plexopathy
      (RIBP) and tumor-related brachial plexopathy (TRBP) and associated dosimetric
      parameters in apical NSCLC patients. METHODS AND MATERIALS: Charts of NSCLC
      patients with primary upper lobe or superiorly located nodal disease who received
      >=50 Gy of definitive conventionally fractionated radiation or chemoradiation
      were retrospectively reviewed for evidence of brachial plexopathy and categorized
      as RIBP, TRBP, or trauma-related. Dosimetric data were gathered on ipsilateral
      brachial plexuses (IBP) contoured according to Radiation Therapy Oncology Group
      atlas guidelines. RESULTS: Eighty patients were identified with a median follow
      up and survival time of 17.2 and 17.7 months, respectively. The median prescribed
      dose was 66.6 Gy (range, 50.4-84.0), and 71% of patients received concurrent
      chemotherapy. RIBP occurred in 5 patients with an estimated 3-year rate of 12%
      when accounting for competing risk of death. Seven patients developed TRBP
      (estimated 3-year rate of 13%), comprising 24% of patients who developed
      locoregional failures. Grade 3 brachial plexopathy was more common in patients
      who experienced TRBP than RIBP (57% vs 20%). No patient who received <=78 Gy to
      the IBP developed RIBP. On multivariable competing risk analysis, IBP V76
      receiving >=1 cc, and primary tumor failure had the highest hazard ratios for
      developing RIBP and TRBP, respectively. CONCLUSIONS: RIBP is a relatively
      uncommon complication in patients with apical NSCLC tumors receiving definitive
      doses of radiation, while patients who develop primary tumor failures are at high
      risk for developing morbid TRBP. These findings suggest that the importance of
      primary tumor control with adequate doses of radiation outweigh the risk of RIBP
      in this population of patients.

PMID- 22658443
TI  - Outcome on home parenteral nutrition for benign intestinal failure: a review of
      the literature and benchmarking with the European prospective survey of ESPEN.
AB  - BACKGROUND & AIMS: Indications and timing for referral for intestinal
      transplantation (ITx) were investigated through a review of the literature on
      home parenteral nutrition (HPN) for benign intestinal failure and a benchmarking
      to the results of a prospective European survey which evaluated the
      appropriateness of the current indications for ITx. METHODS: Manuscripts
      reporting outcomes of adults and children on HPN were retrieved through a PubMed
      search. Data from the European survey were compared with those on HPN reported in
      the literature, and with those on ITx reported by the USA registry and by the
      Pittsburgh center. RESULTS: HPN is a safe treatment with a high probability of
      survival. The risk of death during HPN is increased by the absence of a
      specialist team, and appears greater during the early period of treatment.
      Survival probability is decreased in patients with: age >40 or <2 years, very
      short bowel remnant, presence of a stoma, chronic intestinal pseudo-obstruction
      of myopathic origin, systemic sclerosis, radiation enteritis, intra-abdominal
      desmoids, necrotizing enterocolitis, congenital mucosal diseases. Liver failure
      is the HPN-related complication with the greatest risk of death. Death related to
      venous catheter complications is rare. The benchmarking supported the results of
      the European survey.

PMID- 22658444
TI  - Resting energy expenditure in malnourished older patients at hospital admission
      and three months after discharge: predictive equations versus measurements.
AB  - BACKGROUND: Predicting resting energy expenditure (REE) in malnourished
      hospitalized older patients is important for establishing optimal goals for
      nutritional intake. Measuring REE by indirect calorimetry is hardly feasible in
      most clinical settings. OBJECTIVE: To study the most accurate and precise REE
      predictive equation for malnourished older patients at hospital admission and
      again three months after discharge. DESIGN: Twenty-three equations based on
      weight, height, gender, age, fat free mass (FFM) and/or fat mass (FM) and eleven
      fixed factors of kcal/kg were compared to measured REE. REE was measured by
      indirect calorimetry. Accuracy of REE equations was evaluated by the percentage
      patients predicted within 10% of REE measured, the mean percentage difference
      between predicted and measured values (bias) and the Root Mean Squared prediction
      Error (RMSE). RESULTS: REE was measured in 194 patients at hospital admission
      (mean 1473 kcal/d) and again three months after hospital discharge in 107
      patients (mean 1448 kcal/d). The best equations predicted 40% accuracy at
      hospital admission (Lazzer, FAO/WHO-wh and Owen) and 63% three months after
      discharge (FAO/WHO-wh). Equations combined with FFM, height or illness factor
      predicted slightly better. Fixed factors produce large RMSE's. All predictive
      equations showed proportional bias, with overestimation of low REE values and
      underestimation of high REE values. Correction by regression analysis did not
      improve results. CONCLUSIONS: The REE predictive equations are not adequate to
      predict REE in malnourished hospitalized older patients. There is an urgent need
      for either a new accurate REE predictive equation, or accurate easy-to-use
      equipment to measure REE in clinical practice.

PMID- 22658445
TI  - Dome-shaped macula: a compensatory mechanism in myopic anisometropia?
AB  - The purpose of this article was to describe a patient with dome-shaped macula in
      the setting of mild myopic anisometropia and to speculate regarding the role of
      this feature as a compensatory mechanism in ocular development. The clinical
      records of a 49-year-old woman with this condition were reviewed. Spectral-domain
      optical coherence tomographic images revealed evidence of a dome-shaped macula. B
      scan ultrasonography measured axial lengths of 23.8 mm in the right eye and 22.8
      mm in the left eye. Spherical equivalents were -1.375 and +0.375 in the right and
      left eyes, respectively. Examination of the left eye was unremarkable. Dome
      shaped macula has previously only been described in patients with high myopia.
      These findings support the hypothesis that myopic anisometropia, rather than
      absolute refractive status, is central to the development of dome-shaped macula
      and that this feature represents a protective mechanism aimed at reducing the
      effects of anisometropia.

PMID- 22658446
TI  - Delayed traumatic phacocele following trabeculectomy.
AB  - A 56-year-old woman with a history of trabeculectomy in both eyes sustained blunt
      trauma to the right eye at home. She initially presented with pain, loss of
      vision, total hyphema, and hypotony with no evidence of rupture or tissue
      prolapse. Prompt anterior chamber wash out revealed a partially subluxated
      crystalline lens behind the pupil, but the globe was intact. At 1 month
      postoperatively, subconjunctival displacement of the crystalline lens was
      detected. The patient gave a history of severe bouts of coughing and sneezing a
      few days earlier. During removal of phacocele, the trabeculectomy wound was
      intact with no evidence of leakage. A shallow concentric furrow was noticed
      across the flap approximately 3 mm from the limbus. It is believed that repeat
      trauma pushed the crystalline lens through the weakened trabeculectomy scleral
      flap. The wound later self-sealed.

PMID- 22658447
TI  - Ghrelin regulates Bax and PCNA but not Bcl-2 expressions following scrotal
      hyperthermia in the rat.
AB  - More recently, we have reported the beneficial effects of ghrelin in improvement
      of histopathological features of the rat testis following local heat exposure.
      However, the exact mechanism and the precise role of apoptosis- and proliferation
      specific proteins in this regeneration process remained to be explored. Thus,
      thirty adult male Wistar rats were allotted for the experiment and subdivided
      equally into three groups: control-saline (CS), heat-saline (HS) and heat-ghrelin
      (HG). The scrota of HS and HG groups were immersed once in water bath at 43
      degrees C for 15 min. HG animals received 2 nmol of ghrelin subcutaneously
      immediately after heating every other day until day 60 and the other groups were
      given physiological saline using the same method. The testes of all groups were
      taken after rat killing on days 30 and 60 after heat treatment for
      immunocytochemical detection of pro-apoptotic factor Bax, anti-apoptotic protein
      Bcl-2 and proliferation-associated peptide PCNA in the germ cells. Ghrelin could
      significantly suppress the Bax expression in spermatocytes compared to the HS
      group at day 30 (P<0.05). Likewise, the mean percentages of spermatogonia
      containing Bax substance were lower in ghrelin-exposed animals, however the
      differences were not statistically significant. There were immunoreactive cells
      against Bcl-2 in each germ cell neither in the control nor in the heated animals
      of experimental groups. In contrast, the number of PCNA immunolabeling cells were
      higher in HG group in compared to HS or CS animals on both experimental days
      (P<0.001). Down-regulation of Bax expression concurrent with overexpression of
      PCNA in HG group indicates the ability of ghrelin in acceleration of testicular
      germ cells regeneration following heat stress. These findings indicate that
      ghrelin may be used as a novel and efficient antioxidant agent to induce
      resumption of spermatogenesis upon environmental heat exposure.

PMID- 22658448
TI  - C-reactive protein and procalcitonin during febril attacks in PFAPA syndrome.
AB  - OBJECTIVES: To assess the levels of procalcitonin (PCT) and C-reactive protein
      (CRP) in children diagnosed with PFAPA (periodic fever, aphthous stomatitis,
      pharyngitis, and cervical adenitis) during their febrile attacks. METHODS: 23
      patients with diagnosis of PFAPA included into the study prospectively during a
      three years period. In these patients, CRP and PCT values were recorded during 78
      febrile episodes. Furthermore, 20 patients with diagnosis of pneumonia were
      chosen as a control group and their CRP and PCT values were measured. Normal
      reference values for CRP and PCT were 0-10 mg/L and 0-0.5 ng/mL, respectively.
      RESULTS: Mean CRP and PCT values of patients with PFAPA were 94.8+/-71.6 mg/L and
      0.29+/-0.14 ng/mL, respectively. In control group, mean CRP value was 153.2+/-26
      mg/L and PCT was 1.59+/-0.53 ng/mL. CRP and PCT were high in control group. CRP
      was detected high and PCT was normal in PFAPA. Compared to control group, in
      PFAPA group, CRP values were not significantly (p>0.05) and PCT values were
      significantly lower (p<0.001). CONCLUSION: During febrile episodes in the
      patients with diagnosis of PFAPA, CRP values were substantially elevated, whereas
      PCT values were within normal levels. Concomitant assessment of CRP and PCT in
      addition to clinical diagnostic criteria may be of help in making diagnosis and
      distinguishing febrile attacks from infections. However, studies in larger groups
      are required.

PMID- 22658449
TI  - Rehabilitation of congenital facial palsy with temporalis flap--case series and
      literature review.
AB  - BACKGROUND: Congenital facial paralysis is a rare disorder with an incidence of
      less than 1 in 1000 live births. Several surgical rehabilitation techniques have
      been described, such as free flaps or transpositions of the temporalis muscle. We
      report our experience of transposition of the temporalis muscle in this
      indication. MATERIALS AND METHODS: Retrospective monocentric study between
      January 2005 and December 2009. RESULTS: Five children (mean age at the surgery:
      7.3 years, range 6-13) presenting with a congenital facial paralysis were treated
      by a temporalis muscle transposition during the considered period. An etiological
      assessment was achieved by carrying out a petrous bone CT, a cerebral and petrous
      MRI, and audiometric evaluation. Four patients out of 5 (80%) showed a
      satisfactory and stable functional outcome over time (average follow-up: 26
      months). CONCLUSION: Temporalis muscle transposition is a single-stage procedure,
      easily adapted for the pediatric condition of congenital facial paralysis. It is
      our opinion that this procedure needs to be carried out at the end of the pre
      school period.

PMID- 22658450
TI  - A prospective randomised study comparing the jubilee dressing method to a
      standard adhesive dressing for total hip and knee replacements.
AB  - AIM OF THE STUDY: It is important to reduce potential wound complications in
      total hip and total knee arthroplasty procedures. The purpose of this study was
      to compare the jubilee dressing method to a standard adhesive dressing. METHOD:
      124 patients (62 total hip replacements and 62 total knee replacements) were
      randomly selected to have either a standard adhesive dressing or jubilee method
      dressing. The number of dressing changes, incidence of blistering, leakage,
      appearance of inflammation, infection rate and the average stay in hospital was
      recorded for each patient. RESULTS: The jubilee dressing significantly reduced
      the rate of blistering, leakage and number of dressing changes when compare to a
      traditional adhesive dressing (p < 0.05). The rate of inflammation and average
      length of stay in hospital was not significantly different between the two
      groups. CONCLUSION: The authors recommend the use of this dressing for total hip
      and total knee arthroplasty procedures due to the associated lower complication
      rate.

PMID- 22658451
TI  - Non-reference condition correction factor kNR of typical radiation detectors
      applied for the dosimetry of high-energy photon fields in radiotherapy.
AB  - According to accepted dosimetry protocols, the "radiation quality correction
      factor"k(Q) accounts for the energy-dependent changes of detector responses under
      the conditions of clinical dosimetry for high-energy photon radiations. More
      precisely, a factor k(QR) is valid under reference conditions, i.e. at a point on
      the beam axis at depth 10 cm in a large water phantom, for 10*10 cm(2) field
      size, SSD 100 cm and the given radiation quality with quality index Q. Therefore,
      a further correction factor k(NR) has been introduced to correct for the
      influences of spectral quality changes when detectors are used under non
      reference conditions such as other depths, field sizes and off-axis distances,
      while under reference conditions k(NR) is normalized to unity. In this paper,
      values of k(NR) are calculated for 6 and 15 MV photon beams, using published data
      of the energy-dependent responses of various radiation detectors to monoenergetic
      photon radiations, and weighting these responses with validated photon spectra of
      clinical high-energy photon beams from own Monte-Carlo-calculations for a wide
      variation of the non-reference conditions within a large water phantom. Our
      results confirm the observation by Scarboro et al. [26] that k(NR) can be
      represented by a unique function of the mean energy Em, weighted by the spectral
      photon fluence. Accordingly, the numerical variations of Em with depth, field
      size and off-axis distance have been provided. Throughout all considered
      conditions, the deviations of the k(NR) values from unity are at most 2% for a
      Farmer type ion chamber, and they remain below 15% for the thermoluminescent
      detectors LiF:Mg,Ti and LiF:Mg,Cu,P. For the shielded diode EDP-10, k(NR) varies
      from unity up to 20%, while the unshielded diode EDD-5 shows deviations up to 60%
      in the peripheral region. Thereby, the restricted application field of unshielded
      diodes has been clarified. For small field dosimetry purposes k(NR) can be
      converted into k(NCSF), the non-calibration condition correction factor
      normalized to unity for a 4*4 cm(2) calibration field. For the unshielded Si
      diodes needed in small-field dosimetry, the values of k(NCSF) are closer to unity
      than the associated k(NR) values.

PMID- 22658452
TI  - Letter with respect to the article Tormos et al.

PMID- 22658454
TI  - Increased levetiracetam clearance in pregnancy: is seizure frequency affected?

PMID- 22658455
TI  - The utility of prolonged outpatient ambulatory EEG.
AB  - PURPOSE: ILAE guidelines recommend the use of prolonged EEG where the diagnosis
      of epilepsy or the classification of the seizure syndrome is proving difficult.
      Due to its limited provision, video EEG monitoring is unavailable to many
      patients under investigation(1). The aim of this study was to examine the utility
      of the alternate investigation of outpatient ambulatory EEG. METHODS: In this
      retrospective study we analysed 324 consecutive prolonged outpatient ambulatory
      EEGs lasting 72-96 h (4-5 days), without medication withdrawal. EEG data and the
      clinical record were reviewed to investigate the utility of the investigation.
      RESULTS: Of 324 studies: 219 (68%) studies gave positive data, 116 (36%) showed
      interictal epileptiform discharges (IEDs), 167 (52%) had events. 105 (32%)
      studies were normal. Overall 51% of studies changed management of which 22% of
      studies changed the diagnosis and 29% of studies refined the diagnosis by
      classifying the epilepsy into focal or generalised. CONCLUSION: The present study
      confirms the diagnostic utility of outpatient ambulatory EEG in the diagnosis of
      paroxysmal events.

PMID- 22658456
TI  - Balzac and human gait analysis.
AB  - INTRODUCTION: People have been interested in movement analysis in general, and
      gait analysis in particular, since ancient times. Aristotle, Hippocrates, Galen,
      Leonardo da Vinci and Honore de Balzac all used observation to analyse the gait
      of human beings. The purpose of this study is to compare Honore de Balzac's
      writings with a scientific analysis of human gait. SOURCES: Honore de Balzac's
      Theory of walking and other works by that author referring to gait. DEVELOPMENT:
      Honore de Balzac had an interest in gait analysis, as demonstrated by his
      descriptions of characters which often include references to their way of
      walking. He also wrote a treatise entitled Theory of walking (Theorie de la
      demarche) in which he employed his keen observation skills to define gait using a
      literary style. He stated that the walking process is divided into phases and
      listed the factors that influence gait, such as personality, mood, height,
      weight, profession and social class, and also provided a description of the
      correct way of walking. CONCLUSIONS: Balzac considered gait analysis to be very
      important and this is reflected in both his character descriptions and Theory of
      walking, his analytical observation of gait. In our own technology-dominated
      times, this serves as a reminder of the importance of observation.

PMID- 22658457
TI  - Survival outcomes of bevacizumab beyond progression in metastatic colorectal
      cancer patients treated in US community oncology.
AB  - BACKGROUND: Bevacizumab prolongs OS when added to first- or second-line
      chemotherapy for mCRC. This retrospective analysis evaluated the association
      between the continued use of BBP and survival outcomes in mCRC patients treated
      in a community oncology setting. PATIENTS AND METHODS: Data were derived from the
      US Oncology iKnowMed electronic medical record system. Patients with mCRC who
      received first-line bevacizumab-containing therapy between July 1, 2006 and June
      30, 2009, were dichotomized into 2 second-line treatment cohorts: those receiving
      BBP and No-BBP. Clinical outcomes, including OS and postprogression OS (ppOS;
      time from start of second-line therapy to any-cause death), were calculated using
      Kaplan-Meier methods. A Cox proportional hazards model was used to assess the
      effects of patient and treatment characteristics on survival outcomes, adjusting
      for covariates. RESULTS: Overall, 573 patients met the inclusion criteria for
      analysis-BBP (n = 267) and No-BBP (n = 306). Median OS and ppOS were longer in
      the BBP cohort (27.9 and 14.6 months, respectively) compared with the No-BBP
      cohort (21.4 and 10.1 months). According to multivariate analyses, BBP was
      associated with longer OS (HR, 0.76; 95% CI, 0.61-0.95) and ppOS (HR, 0.74; 95%
      CI, 0.60-0.93) after adjusting for potential confounders. CONCLUSIONS: In the
      community oncology setting, BBP treatment was correlated with prolonged OS and
      ppOS in patients with mCRC. These results provide insight into real-world
      patterns of care and resultant bevacizumab use in this patient population.

PMID- 22658458
TI  - Multiplexed protein signal pathway mapping identifies patients with rectal cancer
      that responds to neoadjuvant treatment.
AB  - BACKGROUND: Currently there is no reliable technique for predicting clinical or
      pathologic complete tumor response after radiochemotherapy (RCT) in patients with
      rectal cancer. We applied reverse phase protein microarray (RPMA) technology to
      find a signal pathway that may predict the response to preoperative treatment.
      PATIENTS AND METHODS: Fifteen rectal cancer samples were collected during
      preoperative RCT. Seven patients had a good response to preoperative therapy
      (Mandard grade I-II) and 8 patients had a poor response (Mandard grade III-V).
      Using laser capture microdissection (LCM) and RPMA analysis, we measured the
      phosphorylation level of nearly 80 end points and analyzed the signaling
      pathways. RESULTS: We identified 4 signaling proteins whose phosphorylation
      levels were significantly different (P < .05) between the good vs. poor
      responders; CHK2 and beta-catenin were more highly phosphorylated in poor
      responders, whereas PDK1 and glycogen synthase kinase (GSK)-3alpha/beta had lower
      phosphorylation levels in poor responders. Interestingly GSK-3alpha/beta, beta
      catenin, and PDK1 are all present in the phosphatidylinositol-3-kinase (PI3K)-AKT
      signaling pathway. CONCLUSIONS: Based on our results, we hypothesize that the
      activating state of the PI3K-AKT pathway can stratify patients who could benefit
      most from neoadjuvant treatment. Moreover, identification of theranostic targets
      has the potential to pinpoint new therapeutic strategies for the nonresponsive
      population.

PMID- 22658459
TI  - Extraction of time activity curves from gated FDG-PET images for small animals'
      heart studies.
AB  - We introduce a new approach to extract the input function and the tissue time
      activity curve from dynamic ECG-gated (18)F-FDG PET images. These curves are
      mandatory to model the myocardium metabolic rate of glucose for heart studies.
      The proposed method utilizes coupled active contours to track the myocardium and
      the blood pool deformations. Furthermore, a statistical approach is developed to
      model the blood and tissue activities and to correct for spillovers. The
      developed algorithm offers a reliable alternative to serial blood sampling for
      small animal cardiac PET studies. Indeed, the calculated MMRG value differs by
      1.54% only from the reference value.

PMID- 22658460
TI  - Bayesian random effect models incorporating real-time weather and traffic data to
      investigate mountainous freeway hazardous factors.
AB  - Freeway crash occurrences are highly influenced by geometric characteristics,
      traffic status, weather conditions and drivers' behavior. For a mountainous
      freeway which suffers from adverse weather conditions, it is critical to
      incorporate real-time weather information and traffic data in the crash frequency
      study. In this paper, a Bayesian inference method was employed to model one
      year's crash data on I-70 in the state of Colorado. Real-time weather and traffic
      variables, along with geometric characteristics variables were evaluated in the
      models. Two scenarios were considered in this study, one seasonal and one crash
      type based case. For the methodology part, the Poisson model and two random
      effect models with a Bayesian inference method were employed and compared in this
      study. Deviance Information Criterion (DIC) was utilized as a comparison factor.
      The correlated random effect models outperformed the others. The results indicate
      that the weather condition variables, especially precipitation, play a key role
      in the crash occurrence models. The conclusions imply that different active
      traffic management strategies should be designed based on seasons, and single
      vehicle crashes have different crash mechanism compared to multi-vehicle crashes.

PMID- 22658461
TI  - Safety countermeasures and crash reduction in New York City--Experience and
      lessons learned.
AB  - Traffic fatalities and injuries constitute a major global public health problem
      and the United States has fallen behind other developed countries in traffic
      safety. Yet, New York City stands out as a traffic safety model in the nation
      with its low fatality rate and its significant reductions in various types of
      crashes. This study develops a safety framework that considers three principal
      axes that affect crashes: why, who, and where. While "why" concerns exposure,
      conflict, and speed, "who" and "where" consider the unique characteristics of the
      road users and the surrounding built environment. Grounded in this safety
      framework, the effectiveness of 13 safety countermeasures and street designs
      installed in New York City between 1990 and 2008 are evaluated using a two group
      pretest-posttest design. The potential regression-to-the-mean problem is
      addressed by applying the ANCOVA regression approach. The results show that
      signal related countermeasures that are designed to reduce conflicts: split phase
      timing, signal installations, all pedestrian phase, and increasing pedestrian
      crossing time, reduce crashes. Traffic calming measures, including road diets,
      are also found to have significant safety benefits. Countermeasures that are
      designed to alert drivers' cognitive attention, such as high visibility
      crosswalks and posted speed limit reduction signs, appear to have a lesser
      effect. The various safety countermeasures implemented in New York City
      considered all three important dimensions in the safety framework: why, who, and
      where. The study suggests these strategies are likely to contribute to the large
      reductions in crashes in New York City. We also demonstrate that a rigorous quasi
      experimental design can be readily deployed in transportation safety evaluation
      studies.

PMID- 22658462
TI  - A spatial and temporal analysis of child pedestrian crashes in Santiago, Chile.
AB  - This paper presents a spatial and temporal analysis of child pedestrian crash
      data in Santiago, Chile during the period 2000-2008. First, this study identified
      seven critical areas with high child pedestrian crash risk employing kernel
      density estimation, and subsequently, statistically significant clusters of the
      main attributes associated to these crashes in each critical area were determined
      in a geographic information systems environment. Moran's I index test identified
      a positive spatial autocorrelation on crash contributing factors, time of day,
      straight road sections and intersections, and roads without traffic signs within
      the critical areas during the studied period, whereas a random spatial pattern
      was identified for crashes related to the age attribute. No statistical
      significance in the spatial relationship was obtained in child pedestrian crashes
      with respect to gender, weekday, and month of the year. The results from this
      research aid in determining the areas in which enhanced school-age child
      pedestrian safety is required by developing and implementing effective
      enforcement, educational, and engineering preventive measures.

PMID- 22658463
TI  - Interventions to evaluate fitness to drive among people with chronic conditions:
      Systematic review of literature.
AB  - When an health condition has been identified, the question of whether to continue
      driving depends not on a medical diagnosis, but on the functional consequences of
      the illness. The complex nature of physical and mental impairments and their
      relationship with safe driving make the availability of evidence based tools
      necessary for health professionals. The review aims at identifying and
      summarizing scientific findings concerning the relationship between
      neuropsychological and clinical screening tests and fitness to drive among people
      with chronic conditions. Studies were searched for driving ability evaluation by
      road test or simulator, clinical/neuropsychological examinations of participants
      with chronic diseases or permanent disablement impairing driving performance,
      primary outcomes as fatal/non-fatal traffic injuries and secondary outcomes as
      fitness to drive assessment. Twenty-seven studies fulfilled the inclusion
      criteria. Some studies included more than one clinical condition. The illness
      investigated were Alzheimer Disease (n=6), Parkinson Disease (n=8),
      Cardiovascular Accident (n=4), Traumatic Brain Injuries (n=3), Sleep Apnea
      Syndrome (n=2), Narcolepsy (n=1), Multiple Sclerosis (n=1) and Hepatic
      Encephalopathy (n=1), comorbidities (n=3). No studies match inclusion criteria
      about Myasthenia Gravis, Diabetes Mellitus, Renal Diseases, Hearing Disorders and
      Sight Diseases. No studies referred to primary outcomes. The selected studies
      provided opposite evidences. It would be reasonable to argue that some clinical
      and neuropsychological tests are effective in predicting fitness to drive even if
      contrasting results support that driving performance decreases as a function of
      clinical and neuropsychological decline in some chronic diseases. Nevertheless we
      found no evidence that clinical and neuropsychological screening tests would lead
      to a reduction in motor vehicle crashes involving chronic disabled drivers. It
      seems necessary to develop tests with proven validity for identifying high-risk
      drivers so that physicians can provide guidance to their patients in chronic
      conditions, and also to medical advisory boards working with licensing offices.

PMID- 22658464
TI  - Dosimetric validation of a redundant independent calculation software for VMAT
      fields.
AB  - A redundant independent dosimetric calculation (RIDC) prior to treatment has
      become a basic part of the QA process for 3D conventional radiotherapy, and is
      strongly recommended in several international publications. On the other hand,
      the rapid growth in the number of intensity modulated treatments has led to a
      significant increase in the workflow associated with QA treatments. Diamond ("K&S
      Associates") is RIDC software which is capable of calculating VMAT (Volumetric
      Modulated Arc Therapy) fields. Modeling, validation and commissioning are
      necessary steps thereby making it a useful tool for VMAT QA. In this paper, a
      procedure for the validation of the calculation algorithm is demonstrated. A set
      3D conventional field was verified in two ways: firstly, a comparison was made
      between Diamond calculations and experimental measures obtaining an average
      deviation of -0.1 +/- 0.7%(1SD), and secondly, a comparison made between Diamond
      and the treatment planning system (TPS) Eclipse, obtaining an average deviation
      of 0.4 +/- 0.8%(1SD). For both steps, a plastic slab phantom was used. VMAT
      validation was carried out by analyzing 59 VMAT plans in two ways: first, Diamond
      calculation versus experimental measurement with an average deviation of -0.2 +/-
      1.7%(1SD), and second, Diamond calculation versus TPS calculation with an average
      deviation of 0.0 +/- 1.6%(1SD). In this phase a homogeneous cylindrical phantom
      was used. These results led us to consider this calculation algorithm validated
      for use in VMAT verifications.

PMID- 22658465
TI  - Simultaneous quantification of metronidazole, tinidazole, ornidazole and
      morinidazole in human saliva.
AB  - The aim of this study was to develop a rapid and sensitive method for the
      simultaneous quantification of metronidazole (MEZ), tinidazole (TNZ), ornidazole
      (ONZ) and morinidazole (MNZ) in human saliva. A reversed-phase high-performance
      liquid chromatography (HPLC) method with ultraviolet (UV) detection at 318 nm was
      carried out on a C18 column, using a mixture of potassium dihydrogen phosphate
      buffer, acetonitrile, and methanol (55:15:30, v/v/v) as a mobile phase with a
      flow rate of 1.0 ml/min. The saliva samples (100 MUl) were firstly deproteinized
      by precipitation with methanol (400 MUl), after which they were centrifuged and
      the supernatants were directly injected into the HPLC system. This method
      produced linear responses in the concentration ranges of 25.2-5040.0, 23.9
      4790.0, 25.4-5080.0, 25.0-5000.0 ng/ml with detection limits of 6.0, 17.6, 10.0
      and 11.3 ng/ml for MEZ, TNZ, ONZ and MNZ (S/N=3), respectively. The methods were
      validated in terms of intra- and inter-batch precision (within 7.3% and 9.1%,
      respectively), accuracy, linearity, recovery and stability. The study proved that
      HPLC is both sensitive and selective for the simultaneous quantification of MEZ,
      TNZ, ONZ and MNZ in human saliva using a single mobile phase.

PMID- 22658466
TI  - Direct pharmacokinetic analysis of puqietinone by in vivo microdialysis sampling
      and turbulent-flow chromatography coupled with liquid chromatography-mass
      spectrometry.
AB  - Sample pretreatment is a key step in bioanalytical process because of possible
      interference and matrix effects in mass spectrometry analysis. In this work, a
      novel strategy towards high speed and sensitivity was developed combining in vivo
      microdialysis (MD) sampling, turbulent-flow chromatography (TFC), and liquid
      chromatography-mass spectrometry (LC-MS). The procedures of cleanup,
      preconcentration, and separation were completed on-line in one step within 10min.
      During the MD optimization procedure, 1% hydroxypropyl-beta-cyclodextrin (HP-beta
      CD) was used to improve the relative recovery of the analyte. Untreated MD
      samples were directly injected, and a TFC precolumn was flushed for 1min with
      aqueous phase of 4mL/min flow rate to desalt and concentrate biosamples. The
      retained analytes were then back-flushed by a switching valve onto a fast LC
      column (4.6mm*50mm, 1.8MUm) for separation. Another diverter valve was employed
      to prevent the HP-beta-CD that interferes with the ESI process from entering the
      MS. Puqietinone, a lipophilic alkaloid from Fritillaria puqiensis, was used as a
      case for validation. Results showed that the limit of quantification for
      puqietinone was 0.10ng/mL, and good linearity (R(2)=0.9993) was maintained over
      the range of 1.02-200.02ng/mL. Accuracy and precision were satisfactory within
      the range of the standard curve. This approach was able to effectively eliminate
      the influences of matrix effect and carry-over as the injection volume increased
      up to 20MUL. The developed method was successfully applied to pharmacokinetic
      study of puqietinone after intravenous administration to rat. Results demonstrate
      the potential of using MD with TFC-LC/MS for in vivo monitoring experiments.

PMID- 22658467
TI  - Quechers methodologies as an alternative to solid phase extraction (SPE) for the
      determination and characterization of residues of cephalosporins in beef muscle
      using LC-MS/MS.
AB  - This work was focused on the comparison of two clean-up methods to be used for
      the simultaneous determination of seven cephalosporins in cow muscle. In
      particular, the performance of novel dispersive solid phase extraction (d-SPE)
      procedures based on QuEChERS methodologies was assessed and compared with
      conventional SPE. The separation and detection of the analytes using both methods
      was carried out by LC-MS/MS to reach enough sensitivity to be compatible with the
      detection of the maximum residue limits (MRL) of cephalosporins as regulated by
      EU directives. The optimization of the clean-up step relied on experimental
      design in order to find the most suitable conditions with a reduced number of
      assays. Besides, multi-objective responses were used to reach an overall
      compromise in the recovery of all analytes simultaneously. The validation of the
      two methods was done according to the Directive 2002/657/EC. Linearity, decision
      limit, detection capability, detection and quantification limits (4-50 MUg kg-1),
      precision (RSD less than 15% except for PIR) and recoveries were determined and
      adequate results with comparable values using QuEChERS and SPE methodologies. LOQ
      were better for SPE method (0.1-10 MUg kg-1) but both methods show LOQ below MRL
      values. Precision was slightly better for the QuEChERS method, that also presents
      better recoveries, higher than 85% except for cephalexin.

PMID- 22658468
TI  - Hospital nursing, care quality, and patient satisfaction: cross-sectional surveys
      of nurses and patients in hospitals in China and Europe.
AB  - BACKGROUND: This study provides a comprehensive evaluation of nurse resources in
      Chinese hospitals and the link between nurse resources and nurse and patient
      outcomes. METHODS: Survey data were used from 9688 nurses and 5786 patients in
      181 Chinese hospitals to estimate associations between nurse workforce
      characteristics and nurse and patient outcomes in China. Nurse and patient
      assessments in China were compared with a similar study in Europe. RESULTS:
      Thirty-eight percent of nurses in China had high burnout and 45% were
      dissatisfied with their jobs. Substantial percentages of nurses described their
      work environment and the quality of care on their unit as poor or fair (61% and
      29%, respectively) and graded their hospital low on patient safety (36%). These
      outcomes tend to be somewhat poorer in China than in Europe, though fewer nurses
      in China gave their hospitals poor safety grades. Nurses in Chinese hospitals
      with better work environments and higher nurse-assessed safety grades had lower
      odds of high burnout and job dissatisfaction (ORs ranged from 0.56 to 0.75) and
      of reporting poor or fair quality patient care (ORs ranged from 0.54 to 0.74),
      and patients in such hospitals were more likely to rate their hospital highly, to
      be satisfied with nursing communications, and to recommend their hospitals
      (significant ORs ranged from 1.24 to 1.40). Higher patient-to-nurse ratios were
      associated with poorer nurse outcomes (each additional patient per nurse
      increases both burnout and dissatisfaction by a factor of 1.04) and higher
      likelihoods of nurses reporting poor or fair quality of care (OR=1.05), but were
      unrelated to patient outcomes. Higher percentages of baccalaureate nurses were
      strongly related to better patient outcomes, with each 10% increase in the
      percent of baccalaureate nurses increasing patient satisfaction, high ratings,
      and willingness to recommend their hospital by factors ranging from 1.11 to 1.13.
      INTERPRETATION: Nursing is important in quality and safety of hospital care and
      in patients' perceptions of their care. Improving quality of hospital work
      environments and expanding the number of baccalaureate-prepared nurses hold
      promise for improving hospital outcomes in China.

PMID- 22658469
TI  - Topical morphine for oral mucositis in children: dose finding and absorption.
AB  - CONTEXT: Systemic opioids for painful chemotherapy-induced oral mucositis in
      children often result in unsatisfactory pain relief and a high frequency of side
      effects. Opioids applied topically can produce analgesia by binding to opioid
      receptors on peripheral terminals of sensory neurons. These receptors are
      upregulated during inflammation, for example, in oral mucositis. OBJECTIVES: The
      aims of this study were to investigate the dose-response relationship (n=7) and
      the potential absorption of topical morphine (n=5) across oral mucosa in children
      with oral mucositis. METHODS: The dose-response study was conducted according to
      a sequential study design (Dixon's Up-and-Down method) for topical morphine doses
      of 0.025-0.400mg/kg, with the decrease in oral pain score as the primary outcome.
      To assess potential absorption across oral mucosa after a single dose of topical
      morphine of 0.050mg/kg, blood samples were drawn and the plasma concentrations of
      morphine and metabolites were determined by high-pressure liquid chromatography.
      RESULTS: A decrease in oral pain score of >=36% was achieved in six of seven
      patients in the dose-response part of the study. Plasma concentrations of
      morphine and metabolites were well below effective analgesic levels. CONCLUSION:
      No obvious dose-response effect was found for topical morphine doses of 0.025
      0.400mg/kg, and topically applied morphine was not absorbed in clinically
      relevant doses. However, this study was limited by the small number of patients
      and the allowance of a systemic opioid as rescue medication. Thus, randomized
      controlled studies are needed to further investigate the analgesic properties of
      topical morphine.

PMID- 22658470
TI  - The experiences of relatives with the practice of palliative sedation: a
      systematic review.
AB  - CONTEXT: Guidelines about palliative sedation typically include recommendations
      to protect the well-being of relatives. OBJECTIVES: The aim of this study was to
      systematically review evidence on the experiences of relatives with the practice
      of palliative sedation. METHODS: PubMed, Embase, Web of Science, PsycINFO, and
      CINAHL were searched for empirical studies on relatives' experiences with
      palliative sedation. We investigated relatives' involvement in the decision
      making and sedation processes, whether they received adequate information and
      support, and relatives' emotions. RESULTS: Of the 564 studies identified, 39 were
      included. The studies (30 quantitative, six qualitative, and three mixed methods)
      were conducted in 16 countries; three studies were based on relatives' reports,
      26 on physicians' and nurses' proxy reports, seven on medical records, and three
      combined different sources. The 39 studies yielded a combined total of 8791
      respondents or studied cases. Caregivers involved relatives in the decision
      making in 69%-100% of all cases (19 quantitative studies), and in 60%-100% of all
      cases, relatives were reported to have received adequate information (five
      quantitative studies). Only two quantitative studies reported on relatives'
      involvement in the provision of sedation. Despite the fact that the majority of
      relatives were reported to be comfortable with the use of palliative sedation
      (seven quantitative studies, four qualitative studies), several studies found
      that relatives were distressed by the use of sedation (five quantitative studies,
      five qualitative studies). No studies reported specifically about the support
      provided to the relatives. CONCLUSION: Relatives' experiences with palliative
      sedation are mainly studied from the perspective of proxies, mostly professional
      caregivers. The majority of relatives seems to be comfortable with the use of
      palliative sedation; however, they may experience substantial distress by the use
      of sedation.

PMID- 22658471
TI  - Prevalence, burden, and correlates of physical and psychological symptoms among
      HIV palliative care patients in sub-Saharan Africa: an international multicenter
      study.
AB  - CONTEXT: Despite HIV remaining life limiting and incurable, very little clinical
      research focus has been given to the prevalence and related burden of physical
      and psychological symptoms for those accessing palliative care. Despite evidence
      of problems persisting throughout the trajectory and alongside treatment, scant
      attention has been paid to these manageable problems. OBJECTIVES: This study
      aimed to measure the seven-day period prevalence and correlates of physical and
      psychological symptoms, and their associated burden, in HIV-infected individuals
      attending palliative care centers in sub-Saharan Africa. METHODS: Consecutive
      patients in five care centers across two countries completed the Memorial Symptom
      Assessment Scale-Short Form, with additional demographic and disease-oriented
      variables. RESULTS: Two hundred twenty-four patients participated. The most
      common symptoms were pain in the physical dimension (82.6%) and worry in the
      psychological dimension (75.4%). Interestingly, 71.4% reported hunger. Women, and
      those with worse physical function, were more likely to experience burden.
      However, being on antiretroviral therapy (ART) was not associated with global,
      physical, or psychological symptom burden. CONCLUSION: This study is the first to
      report physical and psychological symptom burden in HIV-infected populations
      receiving palliative care in sub-Saharan Africa. Despite increasing access to
      ART, these burdensome and manageable problems persist. The assessment of these
      problems is essential alongside assessment of ART virological outcomes.

PMID- 22658472
TI  - Good end-of-life care: perspectives of middle-aged and older Singaporeans.
AB  - CONTEXT: Understanding preferences for end-of-life care is important for planning
      and improving services that provide such care. However, little is known about the
      perspective of Singaporeans regarding good end-of-life care. OBJECTIVES: To
      identify the key components of good end-of-life care as perceived by middle-aged
      and older Singaporeans (>=50 years). METHODS: Nine focus groups were conducted
      with a total of 63 participants. Preferences regarding end-of-life care were
      discussed. Thematic analysis was conducted on the transcribed results of the
      focus groups. RESULTS: Eight components of good end-of-life care were identified:
      1) have physical comfort at the end of life, 2) avoid inappropriate prolongation
      of the dying process, 3) maintain sensitivity toward religious and spiritual
      beliefs, 4) avoid burden on the family, 5) avoid expensive care, 6) be cared for
      by a trustworthy doctor, 7) maintain control over care decisions, and 8) achieve
      a sense of completion. CONCLUSION: Eight components of good end-of-life care
      involving the person, family, and health services were identified among middle
      aged and older Singaporeans. A focus on better management of pain, training of
      caregivers and doctors, shared decision making, and availability of affordable
      care may improve care at the end of life.

PMID- 22658473
TI  - The Spiritual Needs Assessment for Patients (SNAP): development and validation of
      a comprehensive instrument to assess unmet spiritual needs.
AB  - CONTEXT: Unmet spiritual needs have been associated with decreased patient
      ratings of quality of care, satisfaction, and quality of life. There is a need
      for a well-validated, psychometrically sound instrument to describe and measure
      spiritual needs. OBJECTIVES: To develop a valid and reliable instrument to assess
      patients' spiritual needs. METHODS: Instrument development was based on a
      literature review, clinical and pastoral evaluation, and cognitive pretesting
      (n=15 ambulatory cancer patients). Forty-seven ambulatory cancer patients
      completed cross-sectional and longitudinal surveys to test instrument validity
      and reliability. Internal reliability was assessed by Cronbach's alpha, test
      retest reliability by Spearman's correlation coefficients, and construct validity
      by comparing instrument scores to a previously used single-item spiritual needs
      question. RESULTS: The Spiritual Needs Assessment for Patients (SNAP) comprises a
      total of 23 items in three domains: psychosocial (n=5), spiritual (n=13), and
      religious (n=5). Sixty percent of participants were white, 21% black, 13%
      Hispanic, and 6% Asian or other. Fifty-eight percent were Catholic, 13% Jewish,
      11% Protestant, 2% Buddhist, 2% Muslim, and 2% Hindu. Sixty-eight percent
      described themselves as spiritual but not religious; 15% reported unmet spiritual
      needs; 19% wanted help meeting their spiritual needs. Cronbach's alpha for the
      total SNAP was 0.95, and for the subscales was psychosocial=0.74, spiritual=0.93,
      and religious needs=0.86. Test-retest correlation coefficients were total
      SNAP=0.69, psychosocial needs=0.51, spiritual needs=0.70, and religious
      needs=0.65. Participants reporting unmet spiritual needs had significantly higher
      mean scores on the total SNAP (66.3 vs. 49.4, P=0.03) and on the spiritual needs
      subscale (39.0 vs. 28.3, P=0.02). CONCLUSION: The results provide preliminary
      evidence that the SNAP is a valid and reliable instrument for measuring spiritual
      needs in a diverse patient population.

PMID- 22658474
TI  - Mimicking dynamic in vivo environments with stimuli-responsive materials for cell
      culture.
AB  - Traditional synthetic substrates and matrices for cell culture have proven to be
      of only limited utility in efforts to understand and control cell behavior, in
      large part because they fail to capture the multifarious biochemical, mechanical,
      geometric and dynamic characteristics of in vivo environments. However, recent
      advances in materials chemistry and engineering have begun to provide researchers
      with a toolbox to mimic the complex characteristics of natural extracellular
      matrices (ECMs), providing new pathways to explore cell-matrix interactions and
      direct cell fate under physiologically realistic conditions. In this review, we
      describe recent developments in stimuli-responsive materials as dynamic
      substrates and matrices for cell culture, and highlight their use in furthering
      our understanding of how cells respond to temporal variations in their
      environment.

PMID- 22658475
TI  - Hysterectomy subsequent to endometrial ablation.
AB  - STUDY OBJECTIVE: To estimate the incidence of and factors associated with
      hysterectomy subsequent to endometrial ablation. DESIGN: Retrospective cohort
      study (Canadian Task Force classification II-2). SETTING: Gynecology practice.
      PATIENTS: Women who underwent endometrial ablation from January 2003 to June
      2010, with a minimum follow-up of 9 months. INTERVENTIONS: Endometrial ablation
      and hysterectomy. MEASUREMENTS AND MAIN RESULTS: Of 1169 women, 157 (13.4%)
      underwent hysterectomy subsequent to endometrial ablation. Women who underwent
      subsequent hysterectomy were significantly younger at ablation (mean [SD; 95% CI]
      39.0 [6.8; 38.0-40.1] years vs 41.4 [7.0; 41.0-41.9] years; p < .001) and were
      more likely to have previously delivered via cesarean section (26.3 vs 18.1%; p =
      .02). The rate of hysterectomy was significantly associated with the type of
      ablation performed: 33.0% for rollerball vs 16.5% for thermal balloon (p = .003),
      11.0% for radiofrequency (p < .001), and 9.8% for cryoablation (p < .001). Time
      to hysterectomy also differed significantly based on the type of ablation
      performed (p = .006). Adenomyosis was present in 44.4% of hysterectomy specimens.
      CONCLUSION: With a mean follow-up of 39 months, 13.4% of women underwent
      hysterectomy subsequent to ablation. Women who were younger at ablation had an
      increased likelihood of hysterectomy. Rate and time to hysterectomy were
      associated with the type of ablation performed.

PMID- 22658476
TI  - Quantitatively modeling soil-water distribution coefficients of three antibiotics
      using soil physicochemical properties.
AB  - Using 14 parameters featuring soil physicochemical properties and the partial
      least squares (PLSs) regression method, three quantitative models were
      respectively developed for the soil-water distribution coefficients (logK(d)) of
      oxytetracycline (OTC), sulfamethazine (SMZ) and norfloxacin (NOR) in 23 Chinese
      natural soil samples from cultivated lands in 19 provinces of China. The cross
      validated correlation coefficients (Q(cum)(2)) of three models are 0.866, 0.765
      and 0.868, and the standard deviations (SDs) are 0.16, 0.21 and 0.15
      respectively. The high Q(cum)(2) and low SD values indicate that three models
      have high robustness and precise predictability. Six parameters including pH,
      clay content, free Fe oxides (DCB-Fe), free Al oxides (DCB-Al), Ca content and Al
      content are greatly significant in the OTC model, three ones including pH, clay
      content and DCB-Fe are greatly significant in the SMZ model, and five ones
      including pH, clay content, DCB-Fe, Ca content and organic matter (OM) are
      greatly significant in the NOR model. The high VIP values of pH (1.17-1.24), clay
      content (0.81-1.10) and DCB-Fe (0.90-0.99) show that the three sorts of soil
      physicochemical properties play dominant roles in governing the partition balance
      between soil and water of three antibiotics.

PMID- 22658477
TI  - Low-dose intravenous ketamine improves postoperative analgesia after caesarean
      delivery with spinal bupivacaine in African parturients.
AB  - BACKGROUND: In the absence of neuraxial opiates, postoperative analgesia after
      caesarean delivery is limited by the duration of action of bupivacaine. This
      could be prolonged by the co-administration of adjuvants such as ketamine.
      METHODS: Spinal anaesthesia was performed in 60 parturients using hyperbaric
      bupivacaine 15 mg. Patients were randomly allocated to receive a 2-mL intravenous
      injection of either ketamine 0.15 mg/kg (Group BK) or 0.9% saline (Group B)
      immediately after institution of spinal anaesthesia. Postoperative pain was
      assessed using a visual analogue scale and the time of first postoperative
      analgesic administration was noted. Postoperative analgesia was provided with
      intramuscular pentazocine and diclofenac, the total doses of which were recorded
      over 48 h. RESULTS: The mean (SEM) time of first postoperative analgesic
      administration was significantly longer in Group BK (209+/-14.7 min) than in
      Group B (164+/-14.1 min) (P<0.001). Pain scores were significantly lower in Group
      BK than in Group B for 120 min after surgery (P=0.022). Patients in Group BK
      required significantly less diclofenac (P<0.001) and pentazocine (P<0.001) on day
      one after surgery. There was no difference in diclofenac (P=0.302) and
      pentazocine (P=0.092) consumption between the groups on the second postoperative
      day. The incidence of adverse effects was not different between the groups.
      CONCLUSION: The use of intravenous low-dose ketamine as an adjuvant to
      bupivacaine for spinal anaesthesia for caesarean delivery was associated with
      longer postoperative analgesia and lower early postoperative analgesia
      consumption than bupivacaine alone.

PMID- 22658478
TI  - Immunohistochemical study of Dicer and Drosha expression in the benign and
      malignant lesions of gallbladder and their clinicopathological significances.
AB  - Dicer and Drosha are two key enzymes that are involved in the processing of miRNA
      production. Their expressions in gallbladder cancer have not been investigated.
      In this study, we studied Dicer and Drosha expression in 21 non-dysplastic
      gallbladder epithelia and 108 gallbladder adenocarcinomas by immunohistochemical
      staining. The clinicopathological significance of Dicer and Drosha expressions
      was analyzed. We demonstrated that the percent of positive Dicer or Drosha
      expression was significantly lower in gallbladder adenocarcinoma than that in non
      dysplastic gallbladder epithelia (p<0.01). The percent of positive Dicer and
      Drosha expression was significantly lower in poorly differentiated adenocarcinoma
      with lymph node metastasis, invasiveness, and no resection than in well
      differentiated adenocarcinoma without metastasis, invasiveness, and with radical
      resection (p<0.05 or p<0.01). Univariate Kaplan-Meier analysis showed that loss
      of Dicer and Drosha expression was associated with decreased overall survival
      (p<0.05 or p<0.01). Multivariate Cox regression analysis showed that loss of
      Dicer and Drosha expression was an independent poor-prognostic predictor in
      patients with gallbladder adenocarcinoma. In conclusion, loss of Dicer and Drosha
      expression is closely related to the metastasis, invasion, and poor-prognosis in
      gallbladder adenocarcinoma.

PMID- 22658479
TI  - Anisakidosis of the sigmoid colon disguising as metastatic carcinoma: a case
      report and review of the literature.
AB  - Intestinal anisakidosis is a rare nematode infestation caused by the ingestion of
      larvae-infected raw or undercooked fish. Most cases are incidentally diagnosed
      during surgery for other reasons. We present such a case of anisakid larvae seen
      in a patient's sigmoid colon resected for adenocarcinoma, where a subserosal
      nodule caused by the inflammatory reaction to the worm was presumed to be a lymph
      node involved by metastatic tumor. With the increasing popularity of raw fish
      consumption, the incidence of this parasitic infection is bound to increase,
      requiring surgical pathologists to be cognizant of its existence and aware of its
      histologic appearance.

PMID- 22658480
TI  - Transformation of primary myelofibrosis with 20q- in Philadelphia-positive acute
      lymphoblastic leukemia: case report and review of literature.
AB  - A 56-year-old male with chronic idiopathic myelofibrosis and cytogenetic finding
      of 20q- after a period of 10 months developed acute Philadelphia-positive
      lymphoblastic leukemia. Immunophenotyping of peripheral blood by flow cytometry
      showed HLA-DR, CD34, CD19, CD22, CD10, CD33, and CD11b positivity. Cytogenetic
      analysis revealed the presence of 20q- and Philadelphia chromosome
      t(9;22)(q34:q11) at the time of disease transformation to ALL. The JAK2V617F
      mutation was not found. This is a very rare case of simultaneous presence of two
      cytogenetics abnormalities and evolution of primary idiopathic myelofibrosis to
      Philadelphia-positive acute lymphoblastic leukemia.

PMID- 22658481
TI  - CD10 and HHF35 actin in the differential diagnosis between Collagenous
      spherulosis and adenoid-cystic carcinoma of the breast.
AB  - Collagenous Spherulosis (CS) and Adenoid-Cystic Carcinoma (AdCC) of the breast
      consist of cribriform proliferations of epithelial and myoepithelial cells with
      an immunophenotypic overlap of some myoepithelial markers, such as p63 and smooth
      muscle actin (SMA). To our knowledge, CD10 and HHF35 actin have not been assessed
      in the differential diagnosis of these two breast lesions. We performed an
      immunohistochemical study on 6 cases of CS and 9 cases of AdCC. We found CD10,
      muscle-specific actin (HHF35), Estrogen and Progesterone receptors (ER and PR) to
      be strongly expressed in CS, but not in AdCC; C-kit was diffusely positive in
      AdCC and scanty in CS; SMA, p63 and Cytokeratine 5/6 (CK5/6) were positive in
      both. Our results also confirm that AdCC could be true basal-like neoplasia,
      probably arising from a basal stem line tending to divergent differentiation
      toward CK5/6/C-kit+, ER/PR-, epithelial basal-like cell type, and toward a
      myoepitelial-like cell type, with an incomplete SMA/p63+, CD10/HHF35-
      immunophenotype. By contrast, CS is a reactive, benign proliferation of two well
      differentiated cell types: epithelial (ER/PR+, C-kit-) and myoepithelial cells
      with a complete immunophenotype including CD10/HHF35 positivity. Our study
      highlights the usefulness of CD10 and HHF35 in the differential diagnosis and
      helps to understand the histogenesis of the two lesions.

PMID- 22658482
TI  - Adiponectin and skeletal muscle: pathophysiological implications in metabolic
      stress.
AB  - Upregulation of muscular adiponectin could act as a local protective mechanism to
      counteract cellular damage in obesity by weakening inflammation, oxidative
      stress, and apoptosis. To test this hypothesis, adiponectin-knockout (KO) and
      wild-type (WT) mice were fed a Western diet (WD). WT mice under WD conditions
      displayed 63% higher adiponectin expression in myocytes than those under standard
      laboratory diet (SLD) conditions (P = 0.011). WD-fed KO mice exhibited
      approximately threefold larger myocyte degeneration than WT mice (P = 0.003).
      Even under SLD conditions, myotubes of KO mice displayed already moderate
      immunolabeling for markers of oxidative stress (peroxiredoxin-3/5) and for a
      lipid peroxidation product (hydroxynonenal). Expression of tumor necrosis factor
      alpha (TNF-alpha) and caspase-6, a marker of apoptosis, was also present. After
      WD challenge, immunoreactivity for these markers was strong in muscle of KO mice,
      although it was detected to a lesser extent in WT mice. Activation of NF-kappaB
      and caspase-6 doubled in myocytes of WD-fed KO mice when compared to WT mice (P <
      0.001). Furthermore, muscle electrotransfer of the adiponectin gene prevented
      these abnormalities in WD-fed KO mice. Finally, gene abrogation of the
      adiponectin receptor 1 (AdipoR1) by siRNA recapitulated a pro-inflammatory state
      in C2C12 myotubes. Thus, upregulation of muscular adiponectin may be triggered by
      obesity and be crucial locally to counteract oxidative stress, inflammation, and
      apoptosis. These effects operate in an autocrine/paracrine manner via AdipoR1 and
      down-regulation of NF-kappaB signaling.

PMID- 22658483
TI  - The mutation in Chd7 causes misexpression of Bmp4 and developmental defects in
      telencephalic midline.
AB  - Mutations in chromosome-helicase-DNA-binding protein 7 (CHD7) are identified as
      the main cause for CHARGE syndrome (coloboma, heart anomaly, choanal atresia,
      retardation, genital and ear anomalies). Most patients (55% to 85%) with CHARGE
      syndrome display developmental defects in the central nervous system (CNS), of
      which pathology and molecular mechanisms remain unclear. In this study, we report
      a novel mutant mouse strain carrying a nonsense mutation, COA1, in exon4 of Chd7
      gene. Chd7(COA1/+) mice phenocopied human CHARGE syndrome and displayed
      developmental defects in the telencephalic midline, including dilated third and
      lateral ventricles, reduced cerebral cortex, and corpus callosum crossing
      failure. Programed cell death in the telencephalic midline zone of Chd7(COA1/+)
      embryos was impaired, consistent with the incomplete telencephalic medial
      invagination in Chd7(COA1/+) embryos. Interestingly, expression of Bmp4, a signal
      well known to induce forebrain midline cell fate and apoptosis, was down
      regulated and also expanded in the forebrain of Chd7(COA1/+) embryos.
      Furthermore, in vitro studies suggested that CHD7 may directly regulate Bmp4
      expression by binding with an enhancer element downstream of the Bmp4 locus.
      These studies provide novel insight into pathogenesis of CNS anomalies in CHARGE
      syndrome.

PMID- 22658485
TI  - 'Big'-insulin-like growth factor-II signaling is an autocrine survival pathway in
      gastrointestinal stromal tumors.
AB  - New treatment targets need to be identified in gastrointestinal stromal tumors
      (GISTs) to extend the treatment options for patients experiencing failure with
      small-molecule tyrosine kinase inhibitors, such as imatinib. Insulin-like growth
      factor (IGF)-II acts as an autocrine factor in several tumor types by binding to
      IGF receptor type 1 (IGF-1R) and/or the insulin receptor (IR) isoform A. The aim
      of the present study was to investigate the putative role of unprocessed pro-IGF
      II, called 'big'-IGF-II, in GISTs. The imatinib-sensitive GIST882 and imatinib
      resistant GIST48 cell lines secrete high levels of big-IGF-II as demonstrated by
      ELISA and Western blotting analyses. IR isoform A mRNA and protein expression,
      but not that of IGF-1R, was found in these KIT mutant cell lines and in KIT and
      platelet-derived growth factor receptor alpha-mutant GIST specimens. Down
      regulation of either big-IGF-II or IR affected AKT and MAPK signaling and reduced
      survival in both cell lines. Disruption of big-IGF-II signaling in combination
      with imatinib had additive cytotoxic effects on GIST882 cells. IGF-II mRNA as
      determined by in situ hybridization was present in 91% of 60 primary GISTs.
      Immunohistochemical analysis of big-IGF-II protein expression was associated with
      moderate- to high-risk tumors compared with tumors with a lower risk
      classification (P < 0.028). Our data put forth the big-IGF-II/IR isoform A axis
      as an autocrine survival pathway and potential therapeutic target in GISTs.

PMID- 22658484
TI  - Prolactin promotes mammary pathogenesis independently from cyclin D1.
AB  - Epidemiological and experimental studies have revealed an important role for
      prolactin (PRL) in breast cancer. Cyclin D1 is a major downstream target of PRL
      in lobuloalveolar development during pregnancy and is amplified and/or
      overexpressed in many breast carcinomas. To examine the importance of cyclin D1
      in PRL-induced pathogenesis, we generated transgenic mice (NRL-PRL) that
      overexpress PRL in mammary epithelial cells, with wild-type, heterozygous, or
      genetically ablated cyclin D1 in the FVB/N genetic background. Although loss of
      one cyclin D1 allele did not affect PRL-induced mammary lesions in nonparous
      females, the complete absence of cyclin D1 (D1(-/-)) markedly decreased tumor
      incidence. Nevertheless, NRL-PRL/D1(-/-) females developed significantly more
      preneoplastic lesions (eg, epithelial hyperplasias and mammary intraepithelial
      neoplasias) than D1(-/-) females. Moreover, although lack of cyclin D1 reduced
      proliferation of morphologically normal mammary epithelium, transgenic PRL
      restored it to rates of wild-type females. PRL posttranscriptionally increased
      nuclear cyclin D3 protein in D1(-/-) luminal cells, indicating one compensatory
      mechanism. Consistently, pregnancy induced extensive lobuloalveolar growth in the
      absence of cyclin D1. However, transcripts for milk proteins were reduced, and
      pups failed to survive, suggesting that mammary differentiation was inadequate.
      Together, these results indicate that cyclin D1 is an important, but not
      essential, mediator of PRL-induced mammary proliferation and pathology in FVB/N
      mice and is critical for differentiation and lactation.

PMID- 22658486
TI  - Role of SOCS2 in modulating heart damage and function in a murine model of acute
      Chagas disease.
AB  - Infection with Trypanosoma cruzi induces inflammation, which limits parasite
      proliferation but may result in chagasic heart disease. Suppressor of cytokine
      signaling 2 (SOCS2) is a regulator of immune responses and may therefore
      participate in the pathogenesis of T. cruzi infection. SOCS2 is expressed during
      T. cruzi infection, and its expression is partially reduced in infected 5
      lipoxygenase-deficient [knockout (KO)] mice. In SOCS2 KO mice, there was a
      reduction in both parasitemia and the expression of interferon-gamma (IFN-gamma),
      tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-10, SOCS1, and SOCS3 in the
      spleen. Expression of IFN-gamma, TNF-alpha, SOCS1, and SOCS3 was also reduced in
      the hearts of infected SOCS2 KO mice. There was an increase in the generation and
      expansion of T regulatory (Treg) cells and a decrease in the number of memory
      cells in T. cruzi-infected SOCS2 KO mice. Levels of lipoxinA(4) (LXA(4))
      increased in these mice. Echocardiography studies demonstrated an impairment of
      cardiac function in T. cruzi-infected SOCS2 KO mice. There were also changes in
      calcium handling and in action potential waveforms, and reduced outward potassium
      currents in isolated cardiac myocytes. Our data suggest that reductions of
      inflammation and parasitemia in infected SOCS2-deficient mice may be secondary to
      the increases in Treg cells and LXA(4) levels. This occurs at the cost of greater
      infection-associated heart dysfunction, highlighting the relevance of balanced
      inflammatory and immune responses in preventing severe T. cruzi-induced disease.

PMID- 22658488
TI  - Cushing's disease presenting with pituitary apoplexy.
AB  - Pituitary tumour apoplexy is a rare but life threatening condition. Cushing's
      disease usually presents with clinical features of Cushing's syndrome. We report
      a 30-year-old male patient with Cushing's disease who presented with severe
      headache and right third nerve palsy. MRI of the pituitary gland revealed a
      pituitary adenoma with infarction suggestive of apoplexy. After a transsphenoidal
      surgery he developed pan-hypopituitarism with diabetes insipidus. We also review
      the relevant literature.

PMID- 22658489
TI  - Ventriculoperitoneal shunt for intracranial hypertension in cryptococcal
      meningitis without hydrocephalus.
AB  - The use of a ventriculoperitoneal (VP) shunt to treat uncontrollable intracranial
      hypertension in patients with cryptococcal meningitis without hydrocephalus is
      somewhat unusual and still largely unreported. However, uncontrollable
      intracranial hypertension without hydrocephalus in these patients is a
      potentially life-threatening condition. Early diagnosis and shunt placement are
      essential to improve survival and neurological function. We report uncontrollable
      intracranial hypertension without hydrocephalus in a 23-year-old woman, which was
      successfully managed by VP shunt placement.

PMID- 22658487
TI  - Solid-phase immunoglobulins IgG and IgM activate macrophages with solid-phase IgM
      acting via a novel scavenger receptor a pathway.
AB  - IgG may accelerate atherosclerosis via ligation of proinflammatory Fcgamma
      receptors; however, IgM is unable to ligate FcgammaR and is often considered
      vasculoprotective. IgM aggravates ischemia-reperfusion injury, and solid-phase
      deposits of pure IgM, as seen with IgM-secreting neoplasms, are well known
      clinically to provoke vascular inflammation. We therefore examined the molecular
      mechanisms by which immunoglobulins can aggravate vascular inflammation, such as
      in atherosclerosis. We compared the ability of fluid- and solid-phase
      immunoglobulins to activate macrophages. Solid-phase immunoglobulins initiated
      prothrombotic and proinflammatory functions in human macrophages, including NF
      kappaB p65 activation, H(2)O(2) secretion, macrophage-induced apoptosis, and
      tissue factor expression. Responses to solid-phase IgG (but not to IgM) were
      blocked by neutralizing antibodies to CD16 (FcgammaRIII), consistent with its
      known role. Macrophages from mice deficient in macrophage scavenger receptor A
      (SR-A; CD204) had absent IgM binding and no activation by solid-phase IgM. RNA
      interference-mediated knockdown of SR-A in human macrophages suppressed
      activation by solid-phase IgM. IgM binding to SR-A was demonstrated by both co
      immunoprecipitation studies and the binding of fluorescently labeled IgM to SR-A
      transfected cells. Immunoglobulins on solid-phase particles around macrophages
      were found in human plaques, increased in ruptured plaques compared with stable
      ones. These observations indicate that solid-phase IgM and IgG can activate
      macrophages and destabilize vulnerable plaques. Solid-phase IgM activates
      macrophages via a novel SR-A pathway.

PMID- 22658490
TI  - Cervical spinal osteosarcoma in an adolescent.
AB  - Primary cervical spine osteosarcoma is rare and is considered to have a poor
      prognosis. We describe an adolescent patient suffering from primary cervical
      spine osteosarcoma with delayed diagnosis. Nineteen months deficit and symptom
      free survival was achieved after an aggressive multi-modality treatment
      comprising surgery and adjuvant chemoradiotherapy.

PMID- 22658491
TI  - Heparin-binding epidermal growth factor-like growth factor protects mesenchymal
      stem cells.
AB  - BACKGROUND: We have previously demonstrated that mesenchymal stem cell (MSC)
      administration protects the intestines from injury in a mouse model of intestinal
      ischemia/reperfusion injury. We have also shown that heparin-binding epidermal
      growth factor-like growth factor (HB-EGF) is a potent intestinal cytoprotective
      agent in vivo that can protect the intestines by way of its effects on stem
      cells. The goal of the present study was to examine the effects of HB-EGF on both
      amniotic fluid (AF)- and bone marrow (BM)-derived MSCs in vitro. METHODS: MSCs
      were isolated from the AF and BM of pan-EGFP mice, grown in MSC-specific culture
      medium, and purified by sequential passages according to their adherence
      properties. Pluripotency was confirmed by induced differentiation. After
      incubation of MSCs with HB-EGF, proliferation was quantified using the CyQuant
      cell proliferation assay kit under normoxic and anoxic conditions. Chemotaxis was
      quantified using the CHEMICON QCM cell migration kit, and apoptosis was
      determined using caspase-3 immunohistochemistry after exposure of the MSCs to
      anoxic stress. RESULTS: AF-MSCs and BM-MSCs showed significantly increased
      proliferation and migration in response to HB-EGF. HB-EGF significantly protected
      AF-MSCs and BM-MSCs from anoxia-induced apoptosis. The proliferative and anti
      apoptotic effects of HB-EGF were even more pronounced in AF-MSCs than in BM-MSCs.
      CONCLUSIONS: These results have demonstrated that HB-EGF acts as a mitogenic and
      chemotactic agent for MSCs that protects MSCs from injury. These findings could
      have important implications for future experiments designed to use MSCs to
      protect the intestines from injury.

PMID- 22658492
TI  - Surgical residents and the adequacy of dictated operative reports.
AB  - INTRODUCTION: The surgeon's clinical note has been previously shown to poorly
      reflect both physician-centered and patient-centered outcomes. We hypothesized
      that dictated operative reports do not adequately demonstrate surgeons' workload,
      preoperative involvement, clinical decision-making, or core competencies.
      MATERIALS AND METHODS: We retrospectively reviewed operative reports in the month
      of January for the years 2007-2011. Operative reports were dictated by interns,
      residents (R1-R5), and surgical staff. All resident reports were approved by
      staff surgeons. We qualitatively assessed each for 15 items that encompassed
      physician-centered outcomes, patient-centered outcomes, and Joint
      Commission/Medicare-required fields. Groups were compared to each other with 1
      way analysis of variance with Bonferroni correction. RESULTS: We reviewed 999
      operative reports. Nearly every chart included an indication and preoperative and
      postoperative diagnoses. Only 57.3% listed whether or not there were any
      complications. Half recorded operative findings. The mean number of fields missed
      based on level of surgical training was R1: 4.83, R2: 4.46, R3: 3.68, R4: 3.35,
      R5: 3.29, and staff: 3.09. Interns and second-year residents missed significantly
      more data fields than upper-level residents and staff (P < 0.0001). Staff
      surgeons missed fewer data fields than third-year residents (P = 0.004). There
      was no statistical difference between R4, R5, and surgical staff (P > 0.999).
      CONCLUSIONS: The dictated operative report does not accurately document
      preoperative surgeon involvement, clinical decision-making, maintenance of core
      competencies, or full compliance with Joint Commission regulations. Focused
      education and enhanced staff oversight of junior-level dictated operative reports
      might be required to improve quality.

PMID- 22658493
TI  - Surgical therapy for epidermoid carcinoma of the anal canal: an NSQIP assessment
      of short-term outcomes.
AB  - BACKGROUND: Although modern therapy for anal canal cancer typically consists of
      combined chemoradiation therapy (CRT), surgery remains an option for patients
      with small lesions, for palliative purposes, and for failure of nonoperative
      management. This study assesses the short-term outcomes of surgical management
      for epidermoid carcinoma of the anal canal using a large nationwide database.
      METHODS: We performed a retrospective review of 30-d outcomes using American
      College of Surgeons National Surgical Quality Improvement Program database (2005
      2009) for all patients with the primary diagnosis of anal canal cancer undergoing
      oncologic or palliative surgery. We defined preoperative CRT using standard
      National Surgical Quality Improvement Program time frames of 30 and 90 d,
      respectively, before surgery. RESULTS: We identified 295 patients (mean age, 58.6
      y; 54% female; 77% white). A total of 34 patients received prior CRT and had age,
      body mass index, American Society of Anesthesiologists class, and preoperative
      laboratory values similar to those without CRT; the only significant differences
      was a lower hematocrit and platelet count in the CRT group. For the entire
      cohort, 30% (N = 89) underwent local excision (LE), 24% (N = 71) diversion, and
      46% (N = 135) abdominoperineal resection (APR). Complications occurred in 23.7%
      of the entire cohort, and overall complication rates significantly differed based
      on the type of procedure [3.4% for LE and 18.3% for diversion, versus 40% for APR
      (P < 0.001)]. Only operative approach significantly affected morbidity, as
      patients receiving APR had a 1.67-fold (range, 1.14-2.45; P = 0.008) increased
      risk of complications. The 30-d mortality for the entire cohort was 2.7%, and was
      highest in the diversion group (7%) compared with the APR (1.5%) and local
      excision groups (1.1%; P = 0.036). However, by multivariate analysis, the only
      factors associated with death were preoperative sepsis (hazard ratio [HR] = 27.5;
      P = 0.005), lack of functional independence (HR = 26.3; P = 0.001), hypertension
      (HR = 14.4; P = 0.028), and prior alcohol use (HR = 21.4; P = 0.026).
      Chemoradiation therapy use did not have a significant effect on complication
      (36.0% versus 40.9%; P = 0.651) or mortality rates (0% versus 1.8%; P = 0.497).
      CONCLUSIONS: Surgical intervention for anal canal cancer remains a necessary
      option for select patients. Morbidity rates vary significantly based on the type
      of treatment; operative approach is the primary factor associated with
      postoperative short-term complications. When surgery is required, recent CRT is
      not associated with a higher complication rate. With proper perioperative care
      and surgical technique, mortality rates remain low, and the increased death rate
      with diversion, even in the short term, likely represents advanced disease.

PMID- 22658494
TI  - Correlation between early sublingual small vessel density and late blood lactate
      level in critically ill surgical patients.
AB  - BACKGROUND: Surgical stress may cause excessive inflammation and lead to
      microcirculatory dysfunction. The hypothesis of this study was that early
      microcirculatory dysfunction may result in anaerobic glycolysis and lead to
      elevated blood lactate levels in patients admitted to surgical intensive care
      units. METHODS: This prospective observational study enrolled adult patients
      admitted to surgical intensive care units after general surgery or thoracic
      surgery. We measured blood lactate levels before the operation and at 1 h and 24
      h after the operation. We obtained images of sublingual microcirculation using a
      sidestream dark field video microscope and analyzed them employing automated
      analysis software. RESULTS: A total of 31 patients completed the study.
      Perioperative total and perfused small vessel densities were lower in patients
      with a blood lactate level >=3 mmol/L. We observed a significant correlation
      between the total small vessel density at 1 h and the blood lactate level at 24 h
      (r = -0.573; P = 0.001). In addition, we saw a significant correlation between
      the perfused small vessel density at 1 h and the blood lactate level at 24 h (r =
      -0.476; P = 0.008). CONCLUSIONS: Early total and perfused small vessel density
      may be used as an early predictor or therapeutic goal for critically ill surgical
      patients in further studies.

PMID- 22658495
TI  - Histologic and immunohistochemical studies of rectus sheath in obese patients.
AB  - BACKGROUND: Obesity is a well-established risk factor for incisional hernia
      development. The exact causative factors have not been clearly defined, and
      development may result from structural disruptions in the connective tissue of
      the fasciae. The goal of this study was to compare the content of elastin in the
      rectus muscle sheath of obese patients and nonobese controls. MATERIALS AND
      METHODS: The study group consisted of 20 patients with body mass index over 35
      kg/m(2) and the control group included 19 patients with normal-range body mass
      index. The biopsy specimens harvested during surgery were subjected to histologic
      evaluation, an immunohistochemical reaction with monoclonal anti-elastin
      antibodies, and the DAB chromatic reaction. The photomicrographs were evaluated
      using ImageJ software and the percentage of the area affected by the color
      reaction was assessed. A statistical evaluation was performed. RESULTS: The
      specimens harvested from persons in the control group showed in hematoxylin-eosin
      staining a high density of fibrous elements, arranged in regular bundles. In
      specimens obtained from the morbidly obese, the density of the fibers was lower
      and their architecture was disrupted; the bundles were thinner and less regularly
      arranged. Most photographs show adipose tissue infiltrating the structure of the
      fascia. Statistical analysis of the percentage of the area occupied by elastin
      showed a statistically significant difference in favor of the controls.
      CONCLUSIONS: The quantitative and qualitative changes in the elastin content of
      rectus abdominis muscle sheath fascia in the obese population may indicate a
      possible local mechanism influencing the development of incisional hernias.

PMID- 22658496
TI  - Congenital maxillomandibular fusion: a report of three cases.
AB  - Congenital fusion of the mandible to the maxilla (syngnathia) is a rare disorder.
      The first case was reported in 1936 and only a few cases have been reported in
      the literature since then. This paper reports three new cases of syngnathia.
      Clinical and radiographic features are presented, as well as surgical management
      and complications.

PMID- 22658497
TI  - Osteoid osteoma associated with the teeth: unusual presentation.
AB  - Osteoid osteoma is a rare benign osseous neoplasm which rarely affects the jaws.
      It is more common in long bones which can lead to postural scoliosis. The
      clinical characteristic feature of this tumour is the unexplained pain that is
      relieved by the intake of analgesics. Histologically it is characterized by the
      formation of central nidus with surrounding sclerotic bone. The diagnostic
      dilemma in this case report is aggravated by its unusual association with the
      teeth. The use of CT scanning is advised to distinguish from other odontogenic
      tumours. Treatment for this tumour is surgical removal or excisional biopsy to
      avoid recurrence and progression to malignant changes.

PMID- 22658498
TI  - Investigation of the interaction between amodiaquine and human serum albumin by
      fluorescence spectroscopy and molecular modeling.
AB  - The interaction of amodiaquine (AQ) with human serum albumin (HSA) has been
      studied by fluorescence spectroscopy. Based on the sign and magnitude of the
      enthalpy and entropy changes (DeltaH(0) = -43.27 kJ mol(-1) and DeltaS(0) = 
      50.03 J mol(-1) K(-1)), hydrogen bond and van der Waals forces were suggested as
      the main interacting forces. Moreover, the efficiency of energy transfer and
      distance between HSA and acceptor AQ was calculated. Finally, the binding of AQ
      to HSA was modeled by molecular docking and molecular dynamic simulation methods.
      Excellent agreement was found between the experimental and theoretical results.
      Both experimental results and modeling methods suggested that AQ binds mainly to
      the sub-domain IIA of HSA.

PMID- 22658499
TI  - [Satisfaction of professionals and users with health services centralisation in
      primary care in summer].

PMID- 22658500
TI  - Multi-technique study of a ceramic archaeological artifact and its content.
AB  - In this paper we report the results of a study performed with different physical
      and chemical methods on a ceramic vase originally attributed to the I century CE.
      The joint use of infrared spectroscopic analysis and laser techniques, as well as
      pyrolysis-gas chromatography coupled with mass spectrometry and
      thermoluminescence, allowed us to characterize the vase material and its content.
      The chemical data were combined with morphological and stylistic examinations of
      the object and helped in defining its actual geographical and chronological
      pertinence.

PMID- 22658501
TI  - Role of botulinum toxin A injection into the submandibular salivary glands as an
      assessment for the subsequent removal of the submandibular glands in the
      management of children with sialorrhoea.
AB  - Sialorrhoea is caused by an excessive production of saliva or a lack of muscular
      coordination at the initiation of the swallowing reflex during the voluntary
      phase. In children with neuromuscular disorders it can cause excoriation and
      social embarrassment. In adults, repeated injections of botulinum have been shown
      to be beneficial in the control of sialorrhoea, but in children, lack of
      cooperation necessitates general anaesthesia, and repeated injections would not
      be appropriate. We aimed to assess outcome after injection of botulinum into the
      submandibular glands to find out whether subsequent removal of the glands would
      reduce salivary flow to an acceptable level. We assessed 30 children with various
      neuromuscular disorders that caused a lack of muscular coordination when
      swallowing. Under general anaesthesia, they all had injection of 1 unit/kg/gland
      of botulinum toxin A (DysportTM, Ipsen Ltd., Slough, UK) into each submandibular
      gland either by bimanual palpation or under ultrasound guidance. They were
      reassessed at 6 weeks to find out whether the flow had reduced adequately or
      whether the mouth was too dry. Twenty-one had improved and of these, 20 went on
      to have the glands removed successfully with no neurological or surgical
      complications. The mouth of one patient had become too dry after injection and
      the parents declined further surgery. The remaining 9 did not improve noticeably
      and continued to be managed medically. Injection of botulinum into the
      submandibular glands gives a reliable assessment of how much the salivary flow
      will be reduced after the submandibular gland has been removed.

PMID- 22658502
TI  - Atrial arrhythmia burden on long-term monitoring in asymptomatic patients late
      after atrial fibrillation ablation.
AB  - Patients appearing free of atrial fibrillation (AF) based on limited
      electrocardiographic monitoring/clinical history late after ablation may still
      have a large silent AF burden and thus have failed ablations and may be at risk
      of thromboembolism. We evaluated long-term monitoring (LTM; 7 days or 1 year) in
      203 patients off antiarrhythmic drugs who were clinically free of AF >1 year
      after ablation. A 7-day monitor was done in 186 and 17 had pacemakers in whom the
      most recent year was analyzed. Arrhythmia recurrence was >30 seconds of AF,
      flutter, or tachycardia. LTM was done 3.1 +/- 1.3 years (range 1.1 to 7.3) after
      the last ablation. AF recurred in only 8 of 186 (4.3%) on 7-day monitoring. One
      had persistent AF. For the other 7, AF burden was 0.0075% to 3.34% with 3 of 7
      having an AF burden <=0.037%. AF recurred in 4 of 17 patients (23.5%) with
      pacemakers. The 4 patients with pacemakers and AF had a 1-year AF burden of
      0.0037% to 0.16%. Given the longer duration of monitoring, pacemakers detected
      more AF than 7-day monitors (p <0.011). AF duration before ablation was the only
      predictor of AF recurrence on LTM (p = 0.01). In patients with symptomatic AF who
      appeared free of AF on clinical grounds an average of 3 years after ablation, AF
      burden on LTM was low. In conclusion, monitoring by implanted devices detects
      more AF than 7-day monitors, most patients exceeding the failure definition of
      >30 seconds have a small AF burden, and when using LTM for follow-up the
      definition of "ablation failure" may be better described by an AF burden >0.5%
      rather than a single 30-second arrhythmia recurrence.

PMID- 22658504
TI  - Editorial comment.

PMID- 22658503
TI  - Clinical characteristics and prevalence of early repolarization associated with
      ventricular arrhythmias following acute ST-elevation myocardial infarction.
AB  - Early repolarization (ER) on a 12-lead electrocardiogram has recently been
      associated with ventricular tachyarrhythmias (VTAs) in patients without
      structural heart disease and in patients with healed myocardial infarction (MI).
      An association between ER and VTAs in the setting of acute ST-segment elevation
      MI (STEMI) has not been explored. In a single-center retrospective case-control
      design, 50 patients with STEMI complicated by VTAs (cases), defined as
      ventricular fibrillation, sustained ventricular tachycardia, or nonsustained
      ventricular tachycardia within 72 hours of the index hospitalization, were
      matched for age and gender with 50 subjects with STEMI without VTAs (controls).
      Electrocardiograms obtained an average of 1 year before STEMI were analyzed for
      ER pattern, defined as notching or slurring of the terminal QRS complex or J
      point elevation >0.1 mV above baseline in >= 2 contiguous leads. A higher
      prevalence of ER was associated with VTAs overall in cases compared to controls
      (26% vs 4%, p = 0.01) and localized to anterior (16% vs 0%) and inferior (14% vs
      2%, p = 0.07) leads but not lateral limb leads. Notching (10% vs 2%, p = 0.1) and
      J-point elevation (16% vs 0%) were more common in cases. Slurring was uncommon.
      ER was associated with VTAs (odds ratio [OR] 6.5, 95% confidence interval [CI]
      1.5 to 28.8, p = 0.01), even after adjustment for creatine kinase-MB (OR 9.2, 95%
      CI 1.6 to 53.4, p = 0.01) and ejection fraction (OR 5.7, 95% CI 1.2 to 27.1, p =
      0.03). In conclusion, ER is associated with VTAs in patients with STEMI even
      after adjustment for left ventricular ejection fraction or creatine kinas-MB
      levels. Larger prospective studies exploring potential associations and
      mechanisms of ventricular arrhythmogenesis with ER pattern are needed.

PMID- 22658505
TI  - Suicidal ideation among patients with bladder pain syndrome/interstitial
      cystitis.
AB  - OBJECTIVE: To estimate the prevalence of suicidal ideation (SI) and compare
      respondents who endorsed SI with respondents who denied SI within a national
      probability sample of women with bladder pain syndrome or interstitial cystitis
      (BPS/IC). METHODS: Data were collected as part of the RAND Interstitial Cystitis
      Epidemiology (RICE) Study, which screened 146,246 US households to identify adult
      women who met BPS/IC symptom criteria. In addition to estimating SI prevalence,
      women with and without recent SI were compared based on demographics, depression
      symptoms, BPS/IC symptoms, functioning, and treatment. RESULTS: Of 1019 women
      with BPS/IC symptoms asked about SI, 11.0% (95% CI = 8.73-13.25) reported SI in
      the past 2 weeks. Those with SI were more likely to be younger, unemployed,
      unmarried, uninsured, less educated, and of lower income. Women who endorsed SI
      reported worse mental health functioning, physical health functioning, and BPS/IC
      symptoms. Women with SI were more likely to have received mental health
      treatment, but did not differ on whether they had received BPS/IC treatment.
      Multivariate logistic regression analyses indicated that severity of BPS/IC
      symptoms did not independently predict likelihood of endorsing SI. CONCLUSION:
      Results suggest that BPS/IC severity may not increase the likelihood of SI except
      via severity of depression symptoms. Additional work is needed to understand how
      to address the increased needs of women with both BPS/IC and SI.

PMID- 22658506
TI  - Virus reduction in an intravenous immunoglobulin by solvent/detergent treatment,
      ion-exchange chromatography and terminal low pH incubation.
AB  - Virus reduction by several steps in the manufacturing process for the intravenous
      immunoglobulin Vigam((r)), has been investigated. The solvent/detergent step
      based on treatment with 0.3% tri-n-butyl phosphate and 1% polysorbate 80 at 37 
      degrees C, was confirmed to be effective for a range of enveloped viruses. Virus
      infectivity was undetectable i.e. >6 log inactivation within 30 min of the
      standard 6 h process. This was consistent over the range of conditions tested
      i.e. solvent/detergent and protein concentration, temperature and pH. The ion
      exchange chromatography step in the process was also able to remove some viruses.
      Virus spiked followed by blank column runs confirmed the effectiveness of the
      sanitisation step for ensuring there was no virus cross contamination between
      column runs. The terminal low pH incubation step was also able to inactivate
      enveloped viruses, as well as some non-enveloped viruses. The combination of
      these three steps ensures a high margin of virus safety for this product.

PMID- 22658508
TI  - Effect of increasing difficulty in standing balance tasks with visual feedback on
      postural sway and EMG: complexity and performance.
AB  - Studies about the relationship between complexity and performance in upright
      standing balance have yielded mixed results and interpretations. The aim of the
      present study was to assess how the increasing difficulty in standing balance
      task affects performance and the complexity of postural sway and neuromuscular
      activation. Thirty-two young healthy participants were asked to stand still on a
      stability platform with visual feedback in three levels of difficulty. EMG
      signals from gastrocnemius medialis, tibialis anterior, rectus femoris and biceps
      femoris were measured with surface electromyography. As task difficulty
      increased, the amplitude of postural sway also increased. In the antero-posterior
      axis, Fuzzy Entropy (complexity) of postural sway decreased from the stable
      condition to the medium instability condition, and increased again at the highest
      instability condition. Fuzzy Entropy in the medio-lateral axis was higher in the
      stable condition; however, no differences were observed between the two
      instability conditions. Lower values of Fuzzy Entropy in postural sway during
      stable condition correlated with greater percent increases in postural sway in
      medio-lateral and antero-posterior axis from the standing still condition to the
      highest instability condition. In addition, mean and coefficient of variation of
      EMG increased and Fuzzy Entropy of EMG decreased when the difficulty in standing
      balance tasks increased. These results suggest that the higher postural sway
      complexity in stable condition, the greater capacity of the postural control
      system to adapt to the platform instability increases. In addition, changes in
      the complexity of EMG modulated by task difficulty do not necessarily reflect
      similar changes on postural sway.

PMID- 22658509
TI  - Electron transfer and biofilm formation of Shewanella putrefaciens as function of
      anode potential.
AB  - Shewanellaceae are among the most widely studied electroactive microorganisms. In
      this report, we studied the influence of the applied electrode potential on the
      anodic current production of Shewanella putrefaciens NCTC 10695 under anoxic
      conditions. Furthermore, we used cyclic voltammetry (CV) and confocal laser
      scanning microscopy (CLSM) to investigate the microbial electron transfer and
      biofilm formation. It is shown that the chronoamperometric current density is
      increasing with increasing electrode potential from 3 MUA cm(-2) at -0.1 V up to 
      12 MUA cm(-2) at +0.4 V (vs. Ag/AgCl), which is accompanied by an increasing
      amount of biomass deposited on the electrode. By means of cyclic voltammetry we
      demonstrate that direct electron transfer (DET) is dominating and the planktonic
      cells play only a minor role.

PMID- 22658507
TI  - Nanopores: A journey towards DNA sequencing.
AB  - Much more than ever, nucleic acids are recognized as key building blocks in many
      of life's processes, and the science of studying these molecular wonders at the
      single-molecule level is thriving. A new method of doing so has been introduced
      in the mid 1990's. This method is exceedingly simple: a nanoscale pore that spans
      across an impermeable thin membrane is placed between two chambers that contain
      an electrolyte, and voltage is applied across the membrane using two electrodes.
      These conditions lead to a steady stream of ion flow across the pore. Nucleic
      acid molecules in solution can be driven through the pore, and structural
      features of the biomolecules are observed as measurable changes in the trans
      membrane ion current. In essence, a nanopore is a high-throughput ion microscope
      and a single-molecule force apparatus. Nanopores are taking center stage as a
      tool that promises to read a DNA sequence, and this promise has resulted in
      overwhelming academic, industrial, and national interest. Regardless of the fate
      of future nanopore applications, in the process of this 16-year-long exploration,
      many studies have validated the indispensability of nanopores in the toolkit of
      single-molecule biophysics. This review surveys past and current studies related
      to nucleic acid biophysics, and will hopefully provoke a discussion of immediate
      and future prospects for the field.

PMID- 22658510
TI  - Packing a punch: the mechanism of pore formation by cholesterol dependent
      cytolysins and membrane attack complex/perforin-like proteins.
AB  - The bacterial cholesterol dependent cytolysins (CDCs) and membrane attack
      complex/perforin-like proteins (MACPF) represent two major branches of a large,
      exceptionally diverged superfamily. Most characterized CDC/MACPF proteins form
      large pores that function in immunity, venoms, and pathogenesis. Extensive
      structural, biochemical and biophysical studies have started to address some of
      the questions surrounding how the soluble, monomeric form of these remarkable
      molecules recognize diverse targets and assemble into oligomeric membrane
      embedded pores. This review explores mechanistic similarities and differences in
      how CDCs and MACPF proteins form pores.

PMID- 22658511
TI  - Vertebral compression fracture (VCF) after spine stereotactic body radiation
      therapy (SBRT): analysis of predictive factors.
AB  - PURPOSE: Vertebral compression fractures (VCFs) are increasingly observed after
      spine stereotactic body radiation therapy (SBRT). The aim of this study was to
      determine the risk of VCF after spine SBRT and identify clinical and dosimetric
      factors predictive for VCF. The analysis incorporated the recently described
      Spinal Instability Neoplastic Score (SINS) criteria. METHODS AND MATERIALS: The
      primary endpoint of this study was the development of a de novo VCF (ie, new
      endplate fracture or collapse deformity) or fracture progression based on an
      existing fracture at the site of treatment after SBRT. We retrospectively scored
      167 spinal segments in 90 patients treated with spine SBRT according to each of
      the 6 SINS criteria. We also evaluated the presence of paraspinal extension,
      prior radiation, various dosimetric parameters including dose per fraction (>=20
      Gy vs <20 Gy), age, and histology. RESULTS: The median follow-up was 7.4 months.
      We identified 19 fractures (11%): 12 de novo fractures (63%) and 7 cases of
      fracture progression (37%). The mean time to fracture after SBRT was 3.3 months
      (range, 0.5-21.6 months). The 1-year fracture-free probability was 87.3%.
      Multivariate analysis confirmed that alignment (P=.0003), lytic lesions (P=.007),
      lung (P=.03) and hepatocellular (P<.0001) primary histologies, and dose per
      fraction of 20 Gy or greater (P=.004) were significant predictors of VCF.
      CONCLUSIONS: The presence of kyphotic/scoliotic deformity and the presence of
      lytic tumor were the only predictive factors of VCF based on the original 6 SINS
      criteria. We also report that patients with lung and hepatocellular tumors and
      treatment with SBRT of 20 Gy or greater in a single fraction are at a higher risk
      of VCF.

PMID- 22658512
TI  - Early salvage hormonal therapy for biochemical failure improved survival in
      prostate cancer patients after neoadjuvant hormonal therapy plus radiation
      therapy--a secondary analysis of irish clinical oncology research group 97-01.
AB  - PURPOSE: To assess the survival benefit of early vs late salvage hormonal therapy
      (HT), we performed a secondary analysis on patients who developed recurrence from
      Irish Clinical Oncology Research Group 97-01, a randomized trial comparing 4 vs 8
      months neoadjuvant HT plus radiation therapy (RT) in intermediate- and high-risk
      prostate adenocarcinoma. METHODS AND MATERIALS: A total of 102 patients from the
      trial who recurred were analyzed at a median follow-up of 8.5 years. The patients
      were divided into 3 groups based on the timing of salvage HT: 57 patients had
      prostate-specific antigen (PSA)<=10 ng/mL and absent distant metastases (group 1,
      early), 21 patients had PSA>10 ng/mL and absent distant metastases (group 2,
      late), and 24 patients had distant metastases (group 3, late). The endpoint
      analyzed was overall survival (OS) calculated from 2 different time points: date
      of enrolment in the trial (OS1) and date of initiation of salvage HT (OS2).
      Survival was estimated using Kaplan-Meier curves and a Cox regression model.
      RESULTS: The OS1 differed significantly between groups (P<.0005): OS1 at 10 years
      was 78% in group 1, 42% in group 2, and 29% in group 3. The OS2 also differed
      significantly between groups (P<.0005): OS2 at 6 years was 70% in group 1, 47% in
      group 2, and 22% in group 3. Group 1 had the longest median time from end of RT
      to biochemical failure compared with groups 2 and 3 (3.3, 0.9, and 1.7 years,
      respectively; P<.0005). Group 1 also had the longest median PSA doubling time
      compared with groups 2 and 3 (9.9, 3.6, and 2.4 months, respectively; P<.0005).
      On multivariate analysis, timing of salvage HT, time from end of RT to
      biochemical failure, and PSA nadir on salvage HT were significant predictors of
      survival. CONCLUSION: Early salvage HT based on PSA<=10 ng/mL and absent distant
      metastases improved survival in patients with prostate cancer after failure of
      initial treatment with neoadjuvant HT plus RT.

PMID- 22658513
TI  - Toward fully automated multicriterial plan generation: a prospective clinical
      study.
AB  - PURPOSE: To prospectively compare plans generated with iCycle, an in-house
      developed algorithm for fully automated multicriterial intensity modulated
      radiation therapy (IMRT) beam profile and beam orientation optimization, with
      plans manually generated by dosimetrists using the clinical treatment planning
      system. METHODS AND MATERIALS: For 20 randomly selected head-and-neck cancer
      patients with various tumor locations (of whom 13 received sequential boost
      treatments), we offered the treating physician the choice between an
      automatically generated iCycle plan and a manually optimized plan using standard
      clinical procedures. Although iCycle used a fixed "wish list" with hard
      constraints and prioritized objectives, the dosimetrists manually selected the
      beam configuration and fine tuned the constraints and objectives for each IMRT
      plan. Dosimetrists were not informed in advance whether a competing iCycle plan
      was made. The 2 plans were simultaneously presented to the physician, who then
      selected the plan to be used for treatment. For the patient group, differences in
      planning target volume coverage and sparing of critical tissues were quantified.
      RESULTS: In 32 of 33 plan comparisons, the physician selected the iCycle plan for
      treatment. This highly consistent preference for the automatically generated
      plans was mainly caused by the improved sparing for the large majority of
      critical structures. With iCycle, the normal tissue complication probabilities
      for the parotid and submandibular glands were reduced by 2.4% +/- 4.9% (maximum,
      18.5%, P=.001) and 6.5% +/- 8.3% (maximum, 27%, P=.005), respectively. The
      reduction in the mean oral cavity dose was 2.8 +/- 2.8 Gy (maximum, 8.1 Gy,
      P=.005). For the swallowing muscles, the esophagus and larynx, the mean dose
      reduction was 3.3 +/- 1.1 Gy (maximum, 9.2 Gy, P<.001). For 15 of the 20
      patients, target coverage was also improved. CONCLUSIONS: In 97% of cases,
      automatically generated plans were selected for treatment because of the superior
      quality. Apart from the improved plan quality, automatic plan generation is
      economically attractive because of the reduced workload.

PMID- 22658514
TI  - Plaque brachytherapy for uveal melanoma: a vision prognostication model.
AB  - PURPOSE: To generate a vision prognostication model after plaque brachytherapy
      for uveal melanoma. METHODS AND MATERIALS: All patients with primary single
      ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106
      plaque brachytherapy between January 1, 2005, and June 30, 2010, were included.
      The primary endpoint was loss of visual acuity. Only patients with initial visual
      acuity better than or equal to 20/50 were used to evaluate visual acuity worse
      than 20/50 at the end of the study, and only patients with initial visual acuity
      better than or equal to 20/200 were used to evaluate visual acuity worse than
      20/200 at the end of the study. Factors analyzed were sex, age, cataracts,
      diabetes, tumor size (basal dimension and apical height), tumor location, and
      radiation dose to the tumor apex, fovea, and optic disc. Univariate and
      multivariable Cox proportional hazards were used to determine the influence of
      baseline patient factors on vision loss. Kaplan-Meier curves (log rank analysis)
      were used to estimate freedom from vision loss. RESULTS: Of 189 patients, 92%
      (174) were alive as of February 1, 2011. At presentation, visual acuity was
      better than or equal to 20/50 and better than or equal to 20/200 in 108 and 173
      patients, respectively. Of these patients, 44.4% (48) had post-treatment visual
      acuity of worse than 20/50 and 25.4% (44) had post-treatment visual acuity worse
      than 20/200. By multivariable analysis, increased age (hazard ratio [HR] of 1.01
      [1.00-1.03], P=.05), increase in tumor height (HR of 1.35 [1.22-1.48], P<.001),
      and a greater total dose to the fovea (HR of 1.01 [1.00-1.01], P<.001) were
      predictive of vision loss. This information was used to develop a nomogram
      predictive of vision loss. CONCLUSIONS: By providing a means to predict vision
      loss at 3 years after treatment, our vision prognostication model can be an
      important tool for patient selection and treatment counseling.

PMID- 22658515
TI  - Outcomes of patients with revised stage I clear cell sarcoma of kidney treated in
      National Wilms Tumor Studies 1-5.
AB  - PURPOSE: To report the clinical outcomes of children with revised stage I clear
      cell sarcoma of the kidney (CCSK) using the National Wilms Tumor Study Group
      (NWTS)-5 staging criteria after multimodality treatment on NWTS 1-5 protocols.
      METHODS AND MATERIALS: All CCSK patients enrolled in the National Wilms Tumor
      Study Group protocols had their pathology slides reviewed, and only those
      determined to have revised stage I tumors according to the NWTS-5 staging
      criteria were included in the present analysis. All patients were treated with
      multimodality therapy according to the NWTS 1-5 protocols. RESULTS: A total of 53
      children were identified as having stage I CCSK. All patients underwent primary
      surgery with radical nephrectomy. The chemotherapy regimens used were as follows:
      regimen A, C, F, or EE in 4 children (8%); regimen DD or DD4A in 33 children
      (62%); regimen J in 4 children (8%); and regimen I in 12 children (22%). Forty
      six patients (87%) received flank radiation therapy (RT). Seven children (13%)
      did not receive flank RT. The median delay between surgery and the initiation of
      RT was 9 days (range, 3-61). The median RT dose was 10.8 Gy (range, 10-36). The
      flank RT doses were as follows: 10.5 or 10.8 Gy in 25 patients (47%), 11-19.9 Gy
      in 2 patients (4%), 20-29.9 Gy in 9 patients (17%), and 30-40 Gy in 10 patients
      (19%). The median follow-up for the entire group was 17 years (range, 2-36). The
      relapse-free and cancer-specific survival rate was 100% at the last follow-up
      examination. CONCLUSIONS: The present results have demonstrated that children
      with revised stage I CCSK using the NWTS-5 staging criteria have excellent
      survival rates despite the use of varying RT doses and chemotherapy regimens in
      the NWTS 1-5 protocols.

PMID- 22658516
TI  - Combining heavy ion radiation and artificial microRNAs to target the homologous
      recombination repair gene efficiently kills human tumor cells.
AB  - PURPOSE: Previously, we demonstrated that heavy ions kill more cells at the same
      dose than X-rays because DNA-clustered lesions produced by heavy ions affect
      nonhomologous end-joining (NHEJ) repair but not homologous recombination repair
      (HRR). We have also shown that our designed artificial microRNAs (amiRs) could
      efficiently target XRCC4 (an essential factor for NHEJ) or XRCC2 (an essential
      factor for HRR) and sensitize human tumor cells to X-rays. Based on these data,
      we were interested in testing the hypothesis that combining heavy ions and amiRs
      to target HRR but not NHEJ should more efficiently kill human tumor cells.
      METHODS AND MATERIALS: Human tumor cell lines (U87MG, a brain tumor cell line,
      and A549, a lung cancer cell line) and their counterparts, overexpressed with
      amiR to target XRCC2, XRCC4 or both, were used in this study. Survival
      sensitivities were examined using a clonogenic assay after these cells were
      exposed to X-rays or heavy ions. In addition, these cell lines were
      subcutaneously injected into nude mice to form xenografts and the tumor size was
      compared after the tumor areas were exposed to X-rays or heavy ions. RESULTS:
      Although targeting either XRCC4 (NHEJ factor) or XRCC2 (HRR factor) sensitized
      the human tumor cells to X-rays, in vitro and the xenograft animal model,
      targeting only XRCC2 but not XRCC4 sensitized the human tumor cells to heavy ions
      in vitro and in the xenograft animal model. CONCLUSIONS: Combining heavy ions
      with targeting the HRR pathway, but not the NHEJ pathway, could significantly
      improve the efficiency of tumor cell death.

PMID- 22658517
TI  - Intensity modulated radiation therapy with dose painting to treat
      rhabdomyosarcoma.
AB  - PURPOSE: To examine local control and patterns of failure in rhabdomyosarcoma
      patients treated with intensity modulated radiation therapy (RT) with dose
      painting (DP-IMRT). PATIENTS AND METHODS: A total of 41 patients underwent DP
      IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery
      with or without intraoperative RT. Fifty-six percent had alveolar histologic
      features. The median interval from beginning chemotherapy to RT was 17 weeks
      (range, 4-25). Very young children who underwent second-look procedures with or
      without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy
      fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of
      36 Gy in 1.8-Gy fractions to at-risk lymph node chains. RESULTS: With 22 months
      of median follow-up, the actuarial local control rate was 90%. Patients aged <=7
      years who received reduced overall and fractional doses had 100% local control,
      and young adults had 79% (P=.07) local control. Three local failures were
      identified in young adults whose primary target volumes had received 50.4 Gy in
      1.8-Gy fractions. CONCLUSIONS: DP-IMRT with lower fractional and cumulative doses
      is feasible for very young children after second-look procedures with or without
      intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with
      aggressive disease who would benefit from prophylactic RT to high-risk lymph node
      chains, although dose escalation might be warranted for improved local control.
      With limited follow-up, it appears that DP-IMRT produces local control rates
      comparable to those of sequential IMRT in patients with rhabdomyosarcoma.

PMID- 22658518
TI  - Feasibility study of glass dosimeter for in vivo measurement: dosimetric
      characterization and clinical application in proton beams.
AB  - PURPOSE: To evaluate the suitability of the GD-301 glass dosimeter for in vivo
      dose verification in proton therapy. METHODS AND MATERIALS: The glass dosimeter
      was analyzed for its dosimetrics characteristic in proton beam. Dosimeters were
      calibrated in a water phantom using a stairlike holder specially designed for
      this study. To determine the accuracy of the glass dosimeter in proton dose
      measurements, we compared the glass dosimeter and thermoluminescent dosimeter
      (TLD) dose measurements using a cylindrical phantom. We investigated the
      feasibility of the glass dosimeter for the measurement of dose distributions near
      the superficial region for proton therapy plans with a varying separation between
      the target volume and the surface of 6 patients. RESULTS AND DISCUSSION:
      Uniformity was within 1.5%. The dose-response has good linearity. Dose-rate,
      fading, and energy dependence were found to be within 3%. The beam profile
      measured using the glass dosimeter was in good agreement with the profile
      obtained from the ionization chamber. Depth-dose distributions in nonmodulated
      and modulated proton beams obtained with the glass dosimeter were estimated to be
      within 3%, which was lower than those with the ionization chamber. In the phantom
      study, the difference of isocenter dose between the delivery dose calculated by
      the treatment planning system and that measured by the glass dosimeter was within
      5%. With in vivo dosimetry, the calculated surface doses overestimated
      measurements by 4%-16% using glass dosimeter and TLD. CONCLUSION: It is
      recommended that bolus be added for these clinical cases. We also believe that
      the glass dosimeter has considerable potential for use with in vivo patient
      proton dosimetry.

PMID- 22658519
TI  - Basal cell adenocarcinoma arising in salivary gland metaplasia of the breast: a
      novel salivary gland-type tumor developing in the breast.
AB  - A variety of salivary gland-type lesions occur in the breast. Three cases of a
      novel mammary carcinoma arising in a background of salivary gland metaplasia and
      morphologically similar to basal cell adenocarcinoma of the salivary gland are
      presented. The clinical presentation, morphologic features, treatment, and follow
      up of these cases are discussed.

PMID- 22658521
TI  - Fusion of dynactin 1 to anaplastic lymphoma kinase in inflammatory
      myofibroblastic tumor.
AB  - Inflammatory myofibroblastic tumor is an uncommon neoplasm that occurs more often
      in younger patients. Approximately 50% of inflammatory myofibroblastic tumors are
      characterized by anaplastic lymphoma kinase fusion genes, more commonly TPM3
      anaplastic lymphoma kinase and TPM4-anaplastic lymphoma kinase. Herein, we report
      a novel fusion of dynactin 1 to anaplastic lymphoma kinase in a neck inflammatory
      myofibroblastic tumor diagnosed in a 7-year-old girl. Histologic evaluation
      showed a perineurioma-like bland spindle cell neoplasm with positive
      immunohistochemical staining for anaplastic lymphoma kinase, S-100, and CD34 but
      negative for epithelial membrane antigen. Standard cytogenetic analysis showed a
      der(2)t(2;12)(p23;q11). Fluorescence in situ hybridization demonstrated
      separation of the anaplastic lymphoma kinase locus. 5'-rapid amplification of
      complementary DNA ends polymerase chain reaction identified an in-frame fusion of
      dynactin 1 exon 16 on chromosome 2 to anaplastic lymphoma kinase exon 20. Reverse
      transcription-polymerase chain reaction with specific primers and direct
      sequencing confirmed the fusion. The structure of the fusion protein retains the
      cytoskeleton-associated protein-glycine domain and coiled coil domain of dynactin
      1 and the receptor tyrosine kinase domain of anaplastic lymphoma kinase. This
      novel fusion gene is structurally similar to other previously described
      anaplastic lymphoma kinase fusion genes and may be associated with the unusual
      morphology and immunophenotype of this tumor.

PMID- 22658522
TI  - Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor
      activation of NF-kappaB.
AB  - The adaptor protein Bcl10 is a critically important mediator of T cell receptor
      (TCR)-to-NF-kappaB signaling. Bcl10 degradation is a poorly understood biological
      phenomenon suggested to reduce TCR activation of NF-kappaB. Here we have shown
      that TCR engagement triggers the degradation of Bcl10 in primary effector T cells
      but not in naive T cells. TCR engagement promoted K63 polyubiquitination of
      Bcl10, causing Bcl10 association with the autophagy adaptor p62. Paradoxically,
      p62 binding was required for both Bcl10 signaling to NF-kappaB and gradual
      degradation of Bcl10 by autophagy. Bcl10 autophagy was highly selective, as shown
      by the fact that it spared Malt1, a direct Bcl10 binding partner. Blockade of
      Bcl10 autophagy enhanced TCR activation of NF-kappaB. Together, these data
      demonstrate that selective autophagy of Bcl10 is a pathway-intrinsic homeostatic
      mechanism that modulates TCR signaling to NF-kappaB in effector T cells. This
      homeostatic process may protect T cells from adverse consequences of unrestrained
      NF-kappaB activation, such as cellular senescence.

PMID- 22658524
TI  - Position statement of the Canadian Society of Clinical Chemists and Canadian
      Association of Medical Biochemists on hemoglobin A1c measurement and reporting.

PMID- 22658523
TI  - Caspase-11 promotes the fusion of phagosomes harboring pathogenic bacteria with
      lysosomes by modulating actin polymerization.
AB  - Inflammasomes are multiprotein complexes that include members of the NLR
      (nucleotide-binding domain leucine-rich repeat containing) family and caspase-1.
      Once bacterial molecules are sensed within the macrophage, the inflammasome is
      assembled, mediating the activation of caspase-1. Caspase-11 mediates caspase-1
      activation in response to lipopolysaccharide and bacterial toxins, and yet its
      role during bacterial infection is unknown. Here, we demonstrated that caspase-11
      was dispensable for caspase-1 activation in response to Legionella, Salmonella,
      Francisella, and Listeria. We also determined that active mouse caspase-11 was
      required for restriction of L. pneumophila infection. Similarly, human caspase-4
      and caspase-5, homologs of mouse caspase-11, cooperated to restrict L.
      pneumophila infection in human macrophages. Caspase-11 promoted the fusion of the
      L. pneumophila vacuole with lysosomes by modulating actin polymerization through
      cofilin. However, caspase-11 was dispensable for the fusion of lysosomes with
      phagosomes containing nonpathogenic bacteria, uncovering a fundamental difference
      in the trafficking of phagosomes according to their cargo.

PMID- 22658525
TI  - Effects of polypharmacy on sleep in psychiatric inpatients.
AB  - The relationship between psychotropic drugs and sleep remains poorly understood.
      In this study, we examined the relationship between the number (and dosage) of
      concurrently-taken antipsychotic medications and sleep in a psychiatric inpatient
      population. Eighty-three long-stay inpatients with severe mental disorders were
      administered the Pittsburgh Sleep Quality Index questionnaire (PSQI). Results
      showed that increasing antipsychotics dosages were linked to better sleep,
      although antipsychotic medications only accounted for a relatively small amount
      of the variance in sleep quality. The results also showed that, when taken in
      combination with several antipsychotics, SSRI/SNRI antidepressants failed to show
      the expected disruptive effects on sleep patterns and daytime functions.
      Altogether, sleep complaints remained pervasive in 70% of this medicated clinical
      sample. This suggests that the use of the sedative properties of antipsychotic
      medication has limited efficacy as a treatment option for sleep dysfunctions, and
      is not an appropriate substitute for other sleep interventions. Altogether, the
      results support the case for more systematic screening and interventions for
      sleep problems in patients with severe psychiatric illness.

PMID- 22658526
TI  - Temporal trends in general and age-specific fertility rates among women with
      schizophrenia (1996-2009): a population-based study in Ontario, Canada.
AB  - PURPOSE: There is substantial evidence that women with schizophrenia in many
      parts of the world have fewer children than their peers. Our objective was to
      analyze recent trends in general and age-specific fertility rates among women
      with schizophrenia in Ontario, Canada. METHODS: We conducted a repeated cross
      sectional population-based study from 1996 to 2009 using population-based linked
      administrative databases for the entire province of Ontario. Women aged 15-49
      years were classified into schizophrenia and non-schizophrenia groups in each
      successive 12-month period. Annual general and age-specific fertility rates were
      derived. RESULTS: The general fertility rate (GFR) among women with schizophrenia
      was 1.16 times higher in 2007-2009 than in 1996-1998 (95% confidence interval
      [CI] 1.04-1.31). The annual GFR ratio of women with vs. without schizophrenia was
      0.41 (95% CI 0.36-0.47) in 2009, which was slightly higher than the same ratio in
      1996 of 0.30 (95% CI 0.25-0.35). Annual age-specific fertility rates (ASFR)
      increased over time among women with schizophrenia aged 20-24, 25-29, 35-39 and
      40-44 years, but the increase was not always statistically significant. Among
      women aged 20-24 years, the ASFR ratio in women with vs. without schizophrenia
      was not significant by the end of the study period (0.93, 95% CI 0.70-1.22).
      CONCLUSIONS: The general fertility rate among women with schizophrenia appears to
      have increased modestly over the past 13 years. Clinical care and health policy
      should consider new strategies that focus on the mental health of women with
      schizophrenia as new mothers, while optimizing healthy pregnancies and child
      rearing.

PMID- 22658527
TI  - Risk factors for relapse following treatment for first episode psychosis: a
      systematic review and meta-analysis of longitudinal studies.
AB  - BACKGROUND: Preventing relapse is an essential element of early intervention in
      psychosis, but relevant risk factors and precise relapse rates remain to be
      clarified. The aim of this study was to systematically compile and analyse risk
      factors for and rates of relapse in the early course of psychosis. METHODS:
      Systematic review and meta-analysis of English and non-English language, peer
      reviewed, longitudinal studies, with a minimum 12-month follow-up and at least
      80% of participants diagnosed with a first episode of psychosis (FEP) that
      reported risk factors for relapse. RESULTS: Of 153 potentially relevant articles,
      29 were included in the study. Pooled prevalence of relapse of positive symptoms
      was 28% (range=12-47%), 43% (35-54%), 54% (40-63%) at 1, 1.5-2, and 3 years
      follow-up, in that order. A total of 109 predictors were analysed, with 24 being
      assessed in at least 3 studies. Of those, 20 predictors could be extracted for
      meta-analysis. Medication non-adherence, persistent substance use disorder,
      carers' critical comments (but not overall expressed emotion) and poorer
      premorbid adjustment, increased the risk for relapse 4-fold, 3-fold, 2.3-fold and
      2.2-fold, respectively. CONCLUSIONS: Clinical variables and general demographic
      variables have little impact on relapse rates. Conversely, non-adherence with
      medication, persistent substance use disorder, carers' criticism and poorer
      premorbid adjustment significantly increase the risk for relapse in FEP. Future
      studies need to address the methodological limitations of the extant research
      (e.g. definition of relapse), focus on the identification of protective factors
      and evaluate theoretically derived models of relapse.

PMID- 22658528
TI  - Response trajectories in "real-world" naturalistically treated schizophrenia
      patients.
AB  - BACKGROUND: To date, research has identified distinct antipsychotic response
      trajectories yet focussing on data from randomized-controlled trials (RCTs).
      Therefore, the heterogeneity of response in "real-world" schizophrenia patients
      is still unknown. METHODS: Antipsychotic response was evaluated in 399 patients
      suffering from a schizophrenia spectrum disorder within a naturalistic
      multicenter study of the Competence Network on Schizophrenia using latent class
      regression. Baseline and illness-related variables were compared between the
      different trajectory classes as well as currently proposed outcome definitions
      (early improvement, response, remission) using univariate tests. In order to
      predict the trajectory group membership classification and regression tree
      analysis were furthermore performed. RESULTS: Five distinct trajectories of
      antipsychotic response were identified: Class 1 (15%) showing an early and
      considerable improvement, Class 2 (14%) incorporating patients with the greatest
      response to treatment, Class 3 (34%) again showing an early improvement to
      treatment yet with a slightly lower degree of improvement, Class 4 (22%)
      featuring patients gradually responding to treatment, and Class 5 (15%) with the
      poorest antipsychotic response. Fewer depressive symptoms at admission, better
      functioning, a shorter duration of illness and less previous hospitalizations
      were found to be significant predictors of good response. No considerable
      differences were found comparing the present results to the previous trajectory
      analyses deriving from RCTs. CONCLUSION: Our results underline the heterogeneous
      course of response independent of the study or treatment design suggesting that
      the diversity in schizophrenia response and outcome is determined primarily by
      different pathophysiological underpinnings.

PMID- 22658529
TI  - [Mesenteric panniculitis].
AB  - Mesenteric panniculitis is a nonspecific inflammatory process affecting the fatty
      tissue at the root of the mesentery. This term is also used to describe the
      clinical and imaging findings in this disorder. Mesenteric panniculitis can be a
      misleading term: it is commonly misused to design an increased density of the
      mesentery without prejudice regarding the etiology. Pain is the main clinical
      symptom. Half of the patients are asymptomatic. There is a palpable mass in half
      of cases. Laboratory tests sometimes reveal an acute phase reaction of varying
      intensity. Mesenteric panniculitis is suspected when CT scan shows increased
      density of the mesenteric fat. Nevertheless, only histological examination could
      establish the diagnosis. Histologic examination may reveal various stages:
      lipodystrophy (the first stage when fat necrosis is predominant), mesenteric
      panniculitis (a majority of infiltrating lymphocytes), sclerosing mesenteritis
      (the end stage when fibrosis is predominant). Histopathologic differential
      diagnoses are lymphomas, lipomas, liposarcomas that can mimic mesenteric
      panniculitis on CT scan. Mesenteric panniculitis is associated with various
      diseases, especially with intra-abdominal inflammatory process. It also can be
      idiopathic. Rare complications can occur with vascular or digestive tract
      compressions. Empirical treatment is only useful in symptomatic patients.
      Colchicine, corticosteroids or immunosuppressive agents can be used. The only
      interest of surgery is the histological confirmation of the diagnosis. A better
      understanding of the pathophysiology of the immunoregulatory functions of adipose
      tissue will improve mesenteric panniculitis management.

PMID- 22658530
TI  - [Neuro-encephalic features of tuberous sclerosis complex].
AB  - Tuberous sclerosis is a phacomatosis resulting from an autosomal dominant
      inheritance. It is characterized by the presence of multiple hamartomas in
      various organs, especially the brain, the skin, the kidneys and the heart. The
      diagnosis of tuberous sclerosis is based on imaging and clinical examination,
      where magnetic resonance imaging constitutes the key investigation showing
      characteristic brain lesions. Neuro-encephalic manifestations may be particularly
      severe, and may even be life threatening. The authors report personal cases
      series and review the literature highlighting epidemiology, clinical features and
      imaging of neuro-encephalic tuberous sclerosis.

PMID- 22658532
TI  - Effects of atorvastatin in the regulation of circulating EPCs and angiogenesis in
      traumatic brain injury in rats.
AB  - Circulating endothelial progenitor cells (EPCs) play an important role in
      angiogenesis and vasculogenesis. Statins administered promote functional
      improvement in rats, independent of their capability to lower cholesterol.
      Whether statin treatment regulates circulating EPCs after traumatic brain injury
      (TBI) has not been investigated. We hypothesized that atorvastatin increases
      circulating EPCs and promotes angiogenesis in TBI rats. Wistar rats (20 months
      old) were subjected to TBI and treated with or without atorvastatin (orally
      administered, 1mg/kg/day) starting 1h after TBI and then daily for 14 consecutive
      days. Long term potentiation (LTP) in the cornu ammonis1 of the hippocampus as
      well as the Modified Neurological Severity Score (mNSS) and the Morris Water Maze
      (MWM) functional tests were performed. Blood circulating EPCs were identified by
      flow cytometry. Rats were sacrificed 25 days after TBI. vWF and CD31
      immunostaining was performed. We found that atorvastatin administration
      significantly induced angiogenesis and increased circulating EPC levels as well
      as improved functional recovery when compared with non-treatment TBI-control rats
      (P<0.05). The circulating EPC level is correlated with vascular density (r=0.878,
      P <0.05) and CD31 positive cell number in the injured brain (r=0.921, P <0.05).
      The results suggest that increasing circulating EPCs with atorvastatin treatment
      may contribute to the observed increase in angiogenesis and improved functional
      outcome after TBI.

PMID- 22658531
TI  - Impaired cognitive function in patients with atherosclerotic carotid stenosis and
      correlation with ultrasound strain measurements.
AB  - INTRODUCTION: It has been postulated that up to 11 million "silent" strokes occur
      annually. While these patients are without classic neurologic deficits, they may
      exhibit cognitive decline. In this study, we examine the cognitive function of
      patients with carotid stenosis. Additionally, we evaluate a noninvasive measure
      of strain in pulsating carotid artery plaques to determine its ability to predict
      cognitive decline. METHODS: We administered the Repeatable Battery for the
      Assessment of Neuropsychological Status (RBANS) to 44 patients with carotid
      stenosis. All patients had stenosis meeting NASCET or ACAS criteria for
      endarterectomy, and were classified as symptomatic or asymptomatic as defined by
      these publications. Age-adjusted scores for each of the 5 RBANS domains
      (immediate memory, visuospatial ability, language, attention, and delayed memory)
      were compared between symptomatic and asymptomatic patients. Mean score for each
      of the 5 domains was then compared to all other domains, regardless of symptom
      status. From this cohort, 23 patients underwent assessment of carotid plaque
      strain by tracking displacements in ultrasound radiofrequency data to estimate
      axial and principal strains over the cardiac cycle. RESULTS: Thirty symptomatic
      and 14 asymptomatic patients were studied. Visuospatial scores were significantly
      lower than any other domain regardless of symptoms (p<0.05 for all pairwise
      comparisons). No other domain score was significantly different from any other.
      In the language domain, asymptomatic patients scored significantly higher than
      symptomatic patients (p<0.05. For all other domains, no difference was found.
      Asymptomatic patients showed a relationship between plaque strain and immediate
      memory (r=-.61, p=ns). Left carotid disease was associated with poorer
      performance across multiple cognitive domains with increasing accumulated strain.
      This was not seen in right carotid disease. CONCLUSION: Patients with large
      carotid plaques (>70% stenosis) exhibit significant difficulties in mental status
      whether classically symptomatic or asymptomatic. While language deficits may be a
      non-specific marker for stroke symptoms, visuospatial deficits are seen before
      classic symptoms, suggesting that carotid disease may become symptomatic earlier
      and more subtly than previously suspected. Abnormal strain distribution with
      pulsation may be related to cognition.

PMID- 22658535
TI  - Polymer conjugates of acridine-type anticancer drugs with pH-controlled
      activation.
AB  - Acridines are potent DNA-intercalating anticancer agents with high in vivo
      anticancer effectiveness, but also severe side effects. We synthesized five 9
      anilinoacridine-type drugs and their conjugates with biocompatible water-soluble
      hydrazide polymer carrier. All of the synthesized acridine drugs retained their
      in vitro antiproliferative properties. Their polymer conjugates were sufficiently
      stable at pH 7.4 (model of pH in blood plasma) while releasing free drugs at pH
      5.0 (model of pH in endosomes). After internalization of the conjugates, the free
      drugs were released and are visible in cell nuclei by fluorescence microscopy.
      Their intercalation ability was proven using a competitive ethidium bromide
      displacement assay.

PMID- 22658536
TI  - Hybridizing ability and nuclease resistance profile of backbone modified cationic
      phosphorothioate oligonucleotides.
AB  - Various stereochemically pure cationic phosphorothioate oligonucleotides bearing
      aminoalkyl moieties were synthesized, and their duplex-forming ability against
      single-stranded DNA (ssDNA), single-stranded RNA (ssRNA) and triplex-forming
      ability against double-stranded DNA (dsDNA) were evaluated by UV melting
      experiments. The cationic Rp stereoisomers showed improved duplex-forming ability
      against ssDNA, triplex-forming ability against dsDNA and nuclease stability.

PMID- 22658533
TI  - Penetrance of LRRK2 G2385R and R1628P is modified by common PD-associated genetic
      variants.
AB  - Variants in the LRRK2 gene are well-characterized genetic predisposing factors
      for PD worldwide, and LRRK2-associated PD is often indistinguishable from
      idiopathic PD (IPD). However, considerable heterogeneity of LRRK2-PD suggests the
      existence of additional genetic and/or environmental modifiers for LRRK2
      carriers, which have yet to be confirmed by large-scale human studies. In a
      Chinese cohort consisting of 2013 sporadic PD patients and 1971 controls, we
      investigated the modification of the two Asian-specific LRRK2 variants, G2385R
      and R1628P, by variants of five other PD-associated genes/loci (SNCA, MAPT, GBA,
      BST1, PARK16). Of all the PD patients, 13.1% carried LRRK2 G2385R and/or R1628P
      variant. Among these carriers, a total of 15 different polygenic genotypes were
      detected representing different combination patterns between LRRK2 variants and
      those of the other genes/loci, which, alone or in combination, significantly
      modified the LRRK2-related risk for PD and the patients' ages at onset (AAOs).
      These results not only represent the largest replication data affirming the
      association between PD and all the six genes/loci in Chinese, but for the first
      time suggest that multiple PD-associated genetic factors modify both the
      penetrance and AAO of LRRK2 parkinsonism. This finding may have important
      implications for elucidating pathophysiologic mechanisms relevant to both LRRK2
      associated and idiopathic PD. However, testing interactions among multiple genes
      by genetic association studies is still challenging. Future studies with much
      larger sample sizes are needed to confirm our findings.

PMID- 22658537
TI  - Natural products as a gold mine for selective matrix metalloproteinases
      inhibitors.
AB  - Nineteen natural compounds with diverse structures are identified as potential
      MMPIs using structure-based virtual screening from 4000 natural products.
      Hydroxycinnamic acid or analogs of natural products are important for potent
      inhibitory and selectivity against MMPs, and the solvent effect in the S1' pocket
      can affect the hydrophobic interactions and hydrogen bonds between MMPIs and
      MMPS, making MMPIs exhibit certain selectivity for a specific MMP isoenzyme.
      Furthermore, compound 5 can reduce the expression of both MMP-2 and active-MMP-9,
      and suppress the migration of MDA-MB-231 tumor cell in a wound healing assay,
      which may be further developed as an anticancer agent.

PMID- 22658538
TI  - Influence of ligand denticity on the properties of novel 99mTc(I)-carbonyl
      complexes. Application to the development of radiopharmaceuticals for imaging
      hypoxic tissue.
AB  - An important issue in the development of metal-based radiopharmaceuticals is the
      selection of the labelling strategy in order to couple the metal to the
      pharmacophore without losing the biological activity. With the aim to evaluate
      the correlation between ligand denticity and biological behaviour of the
      corresponding (99m)Tc complexes, we designed a tridentate and a bidentate 5
      nitroimidazole derivatives suitable for (99m)Tc(I) tricarbonyl complexation and
      with potential use as radiopharmaceuticals towards hypoxic tissue diagnosis.
      Ligands were synthesized using metronidazol, a pharmaceutical containing the
      bioreductive pharmacophore as starting material. The chelating units were
      connected to the pharmacophore using the click reaction of Huisgen. Both (99m)Tc
      complexes were obtained in high yield and were hydrophilic and stable in
      labelling milieu. The complex obtained from the tridentate ligand exhibited high
      stability in human plasma, low protein binding and a favourable biodistribution
      characterized by low blood and liver uptake, fast elimination and negligible
      uptake in other organs or tissues. Selective uptake and retention in tumour
      together with favourable tumour/muscle ratio makes this (99m)Tc-complex a
      promising candidate for further evaluation as potential hypoxia imaging agent in
      tumours. The bidentate ligand, on the other hand, yielded a less stable (99m)Tc
      complex that experimented hydrolysis in vitro and decomposition in human plasma
      and showed high protein binding, high blood and liver uptake and moderate
      excretion. Although selective uptake and retention in tumour was also observed
      physicochemical and biological behaviour are inadequate for in vivo use,
      demonstrating that denticity of the ligand is particularly important and that
      tridentate ligands are preferable in order to prepare (99m)Tc-tricarbonyl
      complexes for Nuclear Medicine imaging.

PMID- 22658540
TI  - Chlorine atom substitution influences radical scavenging activity of 6-chromanol.
AB  - Synthetic 6-chromanol derivatives were prepared with several chlorine
      substitutions, which conferred both electron-withdrawing inductive effects and
      electron-donating resonance effects. A trichlorinated compound (2), a
      dichlorinated compound (3), and three monochlorinated compounds (4, 5, and 6)
      were synthesized; compounds 2, 3, and 6 were novel. The antioxidant activities of
      the compounds, evaluated in terms of their capacities to scavenge galvinoxyl
      radical, were associated with the number and positioning of chlorine atoms in the
      aromatic ring of 6-chromanol. The activity of compound 1 (2,2-dimethyl-6
      chromanol) was slightly higher than the activities of compounds 2 (2,2-dimethyl
      5,7-dichloro-6-chromanol) or 3 (2,2-dimethyl-5,7,8-trichloro-6-chromanol), in
      which the chlorine atoms were ortho to the phenolic hydroxyl group of 6
      chromanol. The scavenging activity of compound 3 was slightly higher than that of
      2, which contained an additional chlorine substituted in the 8 position. The
      activities of polychlorinated compounds 2 and 3 were higher than the activities
      of any of the monochlorinated compounds (4-6). Compound 6, in which a chlorine
      was substituted in the 8 position, exhibited the lowest activity. Substitution of
      a chlorine atom meta to the hydroxyl group of 6-chromanol (compounds 2 and 6)
      decreased galvinoxyl radical scavenging activity, owing to the electron
      withdrawing inductive effect of chlorine. Positioning the chloro group ortho to
      the hydroxyl group (compounds 4 and 5) retained antioxidant activity because the
      intermediate radical was stabilized by the electron-donating resonance effect of
      chlorine in spite of the electron-withdrawing inductive effect of chlorine.
      Antioxidant activities of the synthesized compounds were evaluated for
      correlations with the O-H bond dissociation energies (BDEs) and the ionization
      potentials. The BDEs correlated with the second-order rate constants (k) in the
      reaction between galvinoxyl radical and the chlorinated 6-chromanol derivatives
      in acetonitrile. This indicated that the antioxidant mechanism of the synthesized
      compounds consisted of a one-step hydrogen atom transfer from the phenolic OH
      group rather than an electron transfer followed by a proton transfer. The
      synthesized compounds also exhibited hydroxyl radical scavenging capacities in
      aqueous solution.

PMID- 22658539
TI  - Exploration of the binding proteins of perfluorooctane sulfonate by a T7 phage
      display screen.
AB  - Perfluorooctane sulfonate (PFOS) is a pollutant widely found throughout nature
      and is toxic to animals. We created a PFOS analogue on a polyethylene glycol
      polyacrylamide copolymer and isolated peptides that preferentially bound the PFOS
      analogue using a T7 phage display system. Bioinformatic analysis using the
      FASTAskan program on the RELIC bioinformatics server showed several human
      proteins that likely bound PFOS. Among them, we confirmed binding between PFOS
      and a recombinant soluble form of monocyte differentiation antigen CD14 (sCD14)
      by a surface plasmon biosensor. Furthermore, PFOS inhibited TNF-alpha production
      induced by the sCD14 in mouse macrophage RAW264.7 cells.

PMID- 22658541
TI  - Heat-inducible transgene expression system incorporating a positive feedback loop
      of transcriptional amplification for hyperthermia-induced gene therapy.
AB  - One of the major goals of gene therapy is to regulate the expression of
      therapeutic genes in desired cells or tissues. For this purpose, heat-inducible
      vectors have been exploited for cancer gene therapy combined with hyperthermia,
      which can result in considerable improvement of therapeutic effects. In the
      present study, we constructed a novel heat-inducible gene expression system
      incorporating a transactivation system with a positive feedback loop of
      transcriptional amplification. The target gene expression mediated by the
      transactivator under the control of a heat shock protein 70B' promoter is
      enhanced by self-promoted transactivator gene expression. This expression system
      showed tight control of target gene expression together with high-level
      expression; enhanced expression of the reporter gene was observed in transfected
      cells upon heat treatment, while negligible gene expression was detected in non
      heated cells. When a therapeutic gene was used as the target gene, a considerable
      cytotoxic effect was observed after heat treatment of cancer cells transfected
      with the plasmids. The heat-induced transgene expression system is a promising
      new approach for the development of both a safe and effective vector for
      hyperthermia-based cancer gene therapy.

PMID- 22658542
TI  - [Adolescence, obesity, and the role of lipoprotein lipases in the non-alcoholic
      fatty liver disease].

PMID- 22658543
TI  - Neurohypophyseal germinoma: hCG in cerebrospinal fluid as a key for a diagnostic
      challenge.

PMID- 22658544
TI  - Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome.
AB  - Congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies
      (CLOVES) is a sporadically occurring, nonhereditary disorder characterized by
      asymmetric somatic hypertrophy and anomalies in multiple organs. We hypothesized
      that CLOVES syndrome would be caused by a somatic mutation arising during early
      embryonic development. Therefore, we employed massively parallel sequencing to
      search for somatic mosaic mutations in fresh, frozen, or fixed archival tissue
      from six affected individuals. We identified mutations in PIK3CA in all six
      individuals, and mutant allele frequencies ranged from 3% to 30% in affected
      tissue from multiple embryonic lineages. Interestingly, these same mutations have
      been identified in cancer cells, in which they increase phosphoinositide-3-kinase
      activity. We conclude that CLOVES is caused by postzygotic activating mutations
      in PIK3CA. The application of similar sequencing strategies will probably
      identify additional genetic causes for sporadically occurring, nonheritable
      malformations.

PMID- 22658545
TI  - Genetic architecture of microRNA expression: implications for the transcriptome
      and complex traits.
AB  - We sought to comprehensively and systematically characterize the relationship
      between genetic variation, miRNA expression, and mRNA expression. Genome-wide
      expression profiling of samples of European and African ancestry identified in
      each population hundreds of miRNAs whose increased expression is correlated with
      correspondingly reduced expression of target mRNAs. We scanned 3' UTR SNPs with a
      potential functional effect on miRNA binding for cis-acting expression
      quantitative trait loci (eQTLs) for the corresponding proximal target genes. To
      extend sequence-based, localized analyses of SNP effect on miRNA binding, we
      proceeded to dissect the genetic basis of miRNA expression variation; we mapped
      miRNA expression levels-as quantitative traits-to loci in the genome as miRNA
      eQTLs, demonstrating that miRNA expression is under significant genetic control.
      We found that SNPs associated with miRNA expression are significantly enriched
      with those SNPs already shown to be associated with mRNA. Moreover, we discovered
      that many of the miRNA-associated genetic variations identified in our study are
      associated with a broad spectrum of human complex traits from the National Human
      Genome Research Institute catalog of published genome-wide association studies.
      Experimentally, we replicated miRNA-induced mRNA expression inhibition and the
      cis-eQTL relationship to the target gene for several identified relationships
      among SNPs, miRNAs, and mRNAs in an independent set of samples; furthermore, we
      conducted miRNA overexpression and inhibition experiments to functionally
      validate the miRNA-mRNA relationships. This study extends our understanding of
      the genetic regulation of the transcriptome and suggests that genetic variation
      might underlie observed relationships between miRNAs and mRNAs more commonly than
      has previously been appreciated.

PMID- 22658546
TI  - High levels of discordance between office-based and ambulatory blood pressure
      measurements for diagnosing optimal blood pressure control in high-risk diabetic
      populations from a developing country.
AB  - This study investigated the concordance between office-based blood pressure (BP)
      readings and ambulatory BP monitoring (ABPM) in 51 consenting type 2 diabetes
      patients (25 males) in Cameroon with hypertension who had been receiving stable
      treatment for at least 3 months. The prevalence of optimal BP control was 63%
      based on office measurements and 23% based on ABPM. Agreement between the two
      methods was poor (kappa statistic: 0.15; 95% confidence interval: -0.08 to 0.29).
      Using ABPM as the standard, office BP was helpful for ruling out optimal BP
      control (specificity: 75%), but not for ruling it in (sensitivity: 41%). Our
      results suggest that ABPM should be recommended in such settings as ours only for
      those patients who have already achieved stable optimal BP control according to
      office measurements.

PMID- 22658547
TI  - [Polypoid neuroendocrine tumor of the rectum].

PMID- 22658548
TI  - Comparison of abdominal bloating severity between Irritable Bowel Syndrome
      patients with high and low levels of breath hydrogen excretion in a lactulose
      breath test.
AB  - BACKGROUND: There is growing evidence that gut flora plays a role in the
      development of Irritable Bowel Syndrome (IBS). Abdominal bloating is a common
      symptom in these patients and the severity of this symptom could be related to
      the variations in their fermentative profiles, obtained by measuring the levels
      of breath hydrogen excretion after lactulose ingestion. AIMS: Our objective was
      to determine the difference in abdominal bloating severity between IBS patients
      with high vs low levels of breath hydrogen excretion after lactulose
      administration. METHODS: Lactulose breath tests were carried out on IBS patients
      in our institution between July 2009 and August 2010. Patients were requested to
      fill out a validated questionnaire to assess the severity of their symptoms.
      Abdominal bloating severity score was compared among patients with high and low
      breath hydrogen levels. RESULTS: A total of 234 patients were enrolled. There was
      a statistically significant difference in the abdominal bloating severity score
      between groups: 7.0 (5.7-8.0) vs 6.5 (5.0-7.5), p=0.001. The comparison among IBS
      patients with constipation (IBS-C) in both groups also showed a statistically
      significant difference: 7.5 (6.0-8.5) vs 5.8 (3.5-7.2), p=0.0051. CONCLUSIONS:
      Those patients with a low level of breath hydrogen excretion after lactulose
      ingestion presented with significantly greater abdominal bloating than those with
      a high level of breath hydrogen excretion.

PMID- 22658549
TI  - [Hyperplastic polyp with neoplastic transformation in a patient with atrophic
      gastritis and multiple gastric neuroendocrine tumors].
AB  - Hyperplastic gastric polyps are often found at GI endoscopy and are not
      considered premalignant lesions, although some cases of malignancy have been
      reported. Neuroendocrine tumors, conversely, are rare and account for
      approximately 1% to 2% of gastric polyps. Both hyperplastic gastric polyps and
      neuroendocrine tumors are related to gastric atrophy. The case of a hyperplastic
      polyp with multifocal areas of adenocarcinoma within the polyp associated to
      multiple gastric neuroendocrine tumors is reported.

PMID- 22658550
TI  - An unusual cause of dyspareunia.
AB  - Pancreatic pseudocyst is a complication of acute pancreatitis and it usually
      manifests with abdominal pain. We report the case of a 45-year-old man with a
      history of acute pancreatitis who presented with abdominal pain, dyspareunia, and
      a palpable inguinal mass. Computed tomography scan revealed a large loculated
      pseudocyst that dissected through the pelvic cavity towards the inguinal canal,
      compressing pelvic and inguinal structures. When a patient with a history of
      pancreatitis develops an inguinal mass, a dissecting pancreatic pseudocyst should
      be suspected.

PMID- 22658551
TI  - [Synchronous adenocarcinoma and lymphoepithelioma-like carcinoma in the stomach:
      a case presentation and literature review].
AB  - Gastric cancer is one of the main causes of death in the world. In Venezuela,
      gastric tumors represent 37% of all malignant tumors of the digestive system, but
      only 1,6% to 3,1% of these cases are lymphoepithelioma-like carcinoma.
      Synchronous neoplastic lesions are also rare. The clinical case presented herein,
      a man with two synchronous tumor lesions, is the first of its kind in this
      country. Despite their incipient aspect, the histologic study reported two
      malignant tumors of epithelial origin: well-differentiated adenocarcinoma and
      lymphoepithelioma-like carcinoma.

PMID- 22658552
TI  - Do animal models of vein graft atherosclerosis predict outcomes in man?

PMID- 22658553
TI  - Low plasma testosterone and elevated carotid intima-media thickness: importance
      of low-grade inflammation in elderly men.
AB  - CONTEXT AND OBJECTIVE: An inverse correlation between plasma testosterone levels
      and carotid intima-media thickness (IMT) has been reported in men. We
      investigated whether this association could be mediated or modified by
      traditional cardiovascular risk factors as well as inflammatory status. METHODS:
      In the Three-City population-based cohort study, 354 men aged 65 and over had
      available baseline data on hormones levels and carotid ultrasonography. Plasma
      concentrations of testosterone (total and bioavailable), estradiol and sex
      hormone-binding globulin (SHBG), together with cardiovascular risk factors were
      measured. IMT in plaque-free site and atherosclerotic plaques in the extracranial
      carotid arteries were determined using a standardized protocol. Multiple linear
      regression models were used to analyze this association and interaction study.
      RESULTS: Analyses with and without adjustment for cardiovascular risk factors
      showed that carotid IMT was inversely and significantly correlated with total and
      bioavailable testosterone levels but not with SHBG and estradiol levels. This
      association depended on C-reactive protein (CRP) levels (p for interaction
      <0.05). Among men with low-grade inflammation (CRP >=2 mg/L), mean IMT was higher
      in subjects with bioavailable testosterone <= 3.2 ng/mL than in those with
      bioavailable testosterone > 3.2 ng/mL (0.76 mm and 0.70 mm respectively, p <
      0.01). By contrast, among men with CRP <= 2 mg/L, mean IMT was similar in both
      groups (0.72 mm and 0.71 mm respectively, p = 0.77). Similar results were found
      for total testosterone although not significant. No association was found between
      plasma hormones levels and atherosclerotic plaques. CONCLUSION: In elderly men,
      low plasma testosterone is associated with elevated carotid intima-media
      thickness only in those with low-grade inflammation. Traditional risk factors
      have no mediator role.

PMID- 22658554
TI  - Coronary artery calcium is associated with degree of stenosis and surface
      irregularity of carotid artery.
AB  - OBJECTIVES: Carotid stenosis and plaque stability are critical determinants of
      risk for ischemic stroke. The aim of this study is to elucidate the association
      of CAC with carotid stenosis and plaque characteristics. METHODS: We examined
      data from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort
      study of subclinical cardiovascular disease in multiethnic participants (N =
      6814). The association between CAC measured by computed tomography and carotid
      ultrasonography of carotid plaque was examined using multiple logistic linear
      models adjusting for traditional vascular risk factors including ethnicity. We
      also developed ethnic specific models to compare the relationship between CAC and
      carotid disease across the four ethnicities. RESULTS: Significant carotid
      stenosis was associated with the presence of CAC (OR 1.73; 95% CI, 1.20-2.49) and
      log-transformed Agatston score (OR per 1 point increase, 1.18; 95% CI 1.04-1.35).
      Overt carotid stenosis was also associated with the presence of CAC (OR, 2.34;
      95% CI, 1.93-2.83) and log-transformed Agatston score (OR per 1 point increase,
      1.53; 95% CI 1.38-1.69). Irregular plaque surface was associated with the
      presence of CAC (OR, 1.87; 95% CI 1.50-2.32) and the log-transformed Agatston
      score (OR per 1 point 1 increase, 1.31; 95% CI 1.16-1.48). Associations between
      CAC and stenosis/stability were not different across ethnicities. CONCLUSIONS:
      Both the presence of CAC and log-transferred Agatston score are independently
      associated with significant/overt carotid stenosis and carotid plaque surface
      irregularity regardless of ethnicity. The subjects with a positive or increased
      CAC score are more likely to have carotid disease potentially increasing their
      risk for future ischemic stroke.

PMID- 22658556
TI  - Synthesis and biological evaluation of optically active Ki16425.
AB  - An enantionselective synthesis of both enantiomers of Ki16425, which possesses
      selective LPA antagonistic activity, was achieved. The isoxazole core was
      constructed by a 1,3-dipolar cycloaddition of nitrile oxide with alkyne and
      condensation with the optically active alpha-phenethyl alcohol segment, which was
      prepared by an enantioselective reduction of arylmethylketone. Biological
      evaluation of both enantiomers of Ki16425 revealed that the (R)-isomer showed
      much higher antagonistic activity for LPA(1) and LPA(3) receptors.

PMID- 22658555
TI  - Synthesis of 13C- and 14C-labeled dinucleotide mRNA cap analogues for structural
      and biochemical studies.
AB  - Herein we describe the first simple and short method for specific labeling of
      mono- and trimethylated dinucleotide mRNA cap analogues with (13)C and (14)C
      isotopes. The labels were introduced within the cap structures either at the N7
      for monomethylguanosine cap or N7 and N2 position for trimethylguanosine cap. The
      compounds designed for structural and biochemical studies will be useful tools
      for better understanding the role of the mRNA cap structures in pre-mRNA
      splicing, nucleocytoplasmic transport, translation initiation and mRNA
      degradation.

PMID- 22658557
TI  - Synthesis and biological activity of both enantiomers of kujigamberol isolated
      from 85-million-years-old Kuji amber.
AB  - The full-structure of a norlabdane terpenoid, kujigamberol (1) was determined by
      total synthesis. Key features of the total synthesis are (1) installation of
      isopentyl group through an o-lithiation of benzamide, (2) construction of
      tetralone by the RCM reaction, and (3) optical resolution of (+/-)-1 using
      chromatographical separation of the corresponding camphanates. X-ray
      crystallographical analysis of p-bromobenzoate obtained from the more polar
      camphanate that was identical with a natural derivative, revealed natural
      kujigamberol to have an S-configuration. Both the natural enantiomer and its (R)
      antipode showed the same inhibitory activity toward the mutant yeast and HL-60
      cells, while simple analogs without alkyl groups at the C-8 and 9 positions of
      (+/-)-1 had no such activity.

PMID- 22658558
TI  - Synthesis and evaluation of novel tropane derivatives as potential PET imaging
      agents for the dopamine transporter.
AB  - A novel series of tropane derivatives containing a fluorinated tertiary amino or
      amide at the 2beta position was synthesized, labeled with the positron-emitter
      fluorine-18 (t(1/2)=109.8 min), and tested as potential in vivo dopamine
      transporter (DAT) imaging agents. The corresponding chlorinated analogs were
      prepared and employed as precursors for radiolabeling leading to the fluorine-18
      labeled derivatives via a one-step nucleophilic aliphatic substitution reaction.
      In vitro binding results showed that the 2beta-amino compounds 6b, 6d and 7b
      displayed moderately high affinities to DAT (K(i)<10nM). Biodistribution studies
      of [(18)F]6b and [(18)F]6d showed that the brain uptakes in rats were low. This
      is likely due to their low lipophilicities. Further structural modifications of
      these tropane derivatives will be needed to improve their in vivo properties as
      DAT imaging agents.

PMID- 22658559
TI  - Detecting differentially expressed genes in heterogeneous diseases using control
      only analysis of variance.
AB  - PURPOSE: Microarray technology allows for simultaneously screening many genes and
      determining which gene(s) are differentially expressed in different disease
      statuses or different cell types. The analysis of variance (ANOVA) (for a K
      sample situation with K>2) can be used in such occasions to gauge statistical
      significances. However, the test may be underpowered if the diseases under study
      are heterogeneous. METHODS: The authors propose the "control-only ANOVA" for
      detecting differentially expressed genes in heterogeneous diseases. Monte-Carlo
      simulation shows that the test produces quite accurate type I error rates for
      both normal and non-normal data. The statistical power of the control-only ANOVA
      is higher than that of the conventional ANOVA when the diseases under study are
      heterogeneous. RESULTS: Analysis of a real data set shows that after Bonferroni
      correction, the control-only ANOVA detects three differentially expressed genes,
      whereas the conventional ANOVA can detect only one. CONCLUSIONS: The control-only
      ANOVA is recommended for use when the diseases under study are heterogeneous.

PMID- 22658560
TI  - Three-dimensional echocardiography for the evaluation of left ventricular
      noncompaction.

PMID- 22658562
TI  - Left ventricular systolic dyssynchrony in pediatric and adolescent patients with
      congestive heart failure.

PMID- 22658561
TI  - Increased procollagen type I C-terminal peptide levels indicate diastolic
      dysfunction in end-stage renal disease patients undergoing maintenance dialysis
      therapy.
AB  - BACKGROUND: Cardiac dysfunction is common among patients with end-stage renal
      disease. The aim of this study was to explore the determinants of diastolic
      dysfunction in patients with end-stage renal disease on maintenance hemodialysis.
      METHODS: Patients with asymptomatic end-stage renal disease undergoing
      hemodialysis underwent Doppler tissue imaging analysis and two-dimensional
      speckle-tracking echocardiography with strain analysis. Blood studies included
      albumin, cardiac troponin T, and procollagen type I C-terminal peptide (PICP).
      RESULTS: All enrolled patients had left ventricular (LV) diastolic dysfunction
      and were stratified into two groups by a cutoff value of 13 for the ratio of
      early transmitral flow velocity to the average early diastolic annular velocity
      (E/e'). Seventy-two of the enrolled patients (87%) had grade 1 diastolic
      dysfunction, and 11 patients (13%) had higher grades of diastolic dysfunction.
      The study population did not include a representative sample of patients with the
      pseudonormal or restrictive filling patterns of diastolic dysfunction. There were
      no significant differences in gender, age, LV geometric change, ejection
      fraction, global systolic longitudinal strain and strain rate, and prevalence of
      comorbidities between groups. Patients with average E/e' >= 13 had higher PICP,
      which was significantly correlated with cardiac troponin T, average E/e', and
      systolic circumferential strain rate. By multivariate regression analysis,
      average E/e' level was an independent factor of PICP level (P = .047).
      CONCLUSIONS: Hemodialysis patients with high average E/e' ratios showed increased
      levels of LV filling pressure and higher severity levels of cardiac fibrosis,
      which occurred before the development of systolic dysfunction. PICP was a
      potential indicator of diastolic dysfunction and increased LV filling pressure.

PMID- 22658563
TI  - Early noninvasive evaluation of coronary flow reserve after angioplasty in the
      left anterior descending coronary artery identifies patients at high risk of
      restenosis at follow-up.
AB  - BACKGROUND: Coronary restenosis is the most important clinical limitation after
      percutaneous coronary intervention (PCI), and coronary flow reserve (CFR) is
      reduced in the presence of significant coronary stenosis. This study evaluated
      whether detection of early reduction of Doppler echocardiographically derived CFR
      in the left anterior descending coronary artery can identify patients at high
      risk for developing restenosis after successful PCI. METHODS: Doppler
      echocardiographically derived CFR was studied in 124 consecutive patients at 1
      month and 6-month follow-up after PCI in the left anterior descending coronary
      artery, together with coronary angiography. RESULTS: Restenosis was detected in
      39 angiographic examinations (group A) and no coronary restenosis in the
      remaining 85 (group B) at 6 months. At 1 month, CFR was reduced in group A
      compared with group B (P < .0001), and a significant reduction of CFR in group A
      (P < .0001) but not in group B (P = .89) was detected at 6 months. CFR <= 2.5 at
      1 month was 67% sensitive and 87% specific for predicting significant restenosis,
      with positive and negative predictive values of 67% and 87%, respectively.
      CONCLUSIONS: CFR <= 2.5 detected 1 month after PCI in the left anterior
      descending coronary artery has the potential to identify patients at higher risk
      for developing coronary restenosis and indicates the need for close clinical
      follow-up.

PMID- 22658564
TI  - Left ventricular noncompaction cardiomyopathy.

PMID- 22658565
TI  - Synthesis of three trisaccharide congeners to investigate frame shifting of
      beta1,2-mannan homo-oligomers in an antibody binding site.
AB  - Homopolysaccharides such as the protective beta1,2-mannan present in the cell
      wall of Candida albicans have the capability to bind to antibody in numerous
      frame shifted modes. A protective monoclonal antibody C3.1 binds this antigen and
      exhibits a unique binding profile where di and trisaccharides are the most potent
      inhibitors, while the intrinsic affinities of tetrasaccharide and larger
      oligomers dramatically decrease with increasing chain length. The design,
      synthesis and inhibitory activity of three beta1,2-linked trisaccharide congeners
      is reported. Selective functional group modification was introduced at the
      terminal reducing or non-reducing mannose residues so that each trisaccharide
      would be capable of binding to antibody in only one of the possible frame shifted
      modes. Inhibition data show that C3.1 has the highest affinity for internally
      situated disaccharide epitopes but can bind the terminal non-reducing
      disaccharide of a trisaccharide epitope.

PMID- 22658566
TI  - Autologus transplantation of mononuclear bone marrow cells after acute myocardial
      infarction: a PILOT study.

PMID- 22658567
TI  - Is there a need for adjusting the results of the recent meta-analysis on the
      novel oral anticoagulants in atrial fibrillation to the baseline CHADS2score?

PMID- 22658568
TI  - Paclitaxel coated balloons, the time for awareness has come.
AB  - Over the last decade, a myriad of small clinical studies using a wide variety
      drug coated balloons (DCB) has shown the potential efficacy profile of this
      technology in specific clinical settings, especially coronary in-stent restenosis
      and peripheral artery disease. However, also due to the negative results of some
      small clinical studies, a big sense of confusion and uncertainty still exists
      among device developers and clinicians on current DCB indications. The advantages
      of DCB consist in non-polymeric delivery of anti-proliferative drugs limited to
      the time of the highest activity of the neointimal restenotic process after
      vessel injury, maintenance of vessel anatomy and potential to decrease delayed
      healing. Moreover, this field is rapidly evolving and includes lower-dose
      formulations, dedicated drug delivery reservoirs and alternative drugs. As these
      technologies emerge, we hope that some of the lessons learned will bring to
      proper validation strategies and solid experimental and clinical
      experimentations.

PMID- 22658569
TI  - Plasma glycated albumin level and atherosclerosis: results from the Kyushu and
      Okinawa Population Study (KOPS).
AB  - BACKGROUND: Glycated albumin (GA) is a measure of the mean plasma glucose
      concentration over approximately 2-3 weeks. This study was done to test the
      hypothesis that GA can serve as a marker for atherosclerosis, similar to
      glycosylated hemoglobin A1c (HbA1c). METHODS: HbA1c, plasma GA and serum high
      sensitivity C-reactive protein (hs-CRP) levels were measured for 1575 residents
      (age range 26-78 years) of a suburban town in Japan. Carotid artery intima-media
      thickness (IMT) was measured by ultrasound for each participant. RESULTS: GA
      levels had significantly positive correlation coefficients with HbA1c level, hs
      CRP level, and max-IMT (all P<0.001). Receiver operating characteristic curve
      analysis indicated a GA level of >= 15.5% to be optimal for predicting diabetes.
      A GA level of 15.5% corresponded to an HbA1c level of 5.8%. The hs-CRP and max
      IMT values of participants with GA >= 15.5% were significantly higher than the
      values of those with GA <15.5% (median hs-CRP: 2.4 vs. 2.3mg/L, P=0.048; mean max
      IMT 0.852 vs. 0.759 mm, P=0.003, respectively). Among obese participants, the hs
      CRP and max-IMT values of those with GA >= 15.5% (7.5mg/L and 1.014 mm) were
      significantly higher than the values of those with GA <15.5% (4.7 mg/dL and 0.823
      mm) (P=0.024 and P=0.001, respectively). CONCLUSIONS: Increased IMT and hs-CRP
      levels were associated with a high GA level, especially for obese participants,
      suggesting that GA would be as a useful biomarker for assessing the risk of
      atherosclerosis.

PMID- 22658570
TI  - Hypertensive left ventricular hypertrophy is highly arrhythmogenic--compelling
      indication for some beta blockers?

PMID- 22658571
TI  - Benefits of combined aerobic/resistance/inspiratory training in patients with
      chronic heart failure. A complete exercise model? A prospective randomised study.
AB  - BACKGROUND: We hypothesised that combined aerobic training (AT) with resistance
      training (RT) and inspiratory muscle training (IMT) could result in additional
      benefits over AT alone in patients with chronic heart failure (CHF). METHODS:
      Twenty-seven patients, age 58 +/- 9 years, NYHA II/III and LVEF 29 +/- 7% were
      randomly assigned to a 12-week AT (n=14) or a combined AT/RT/IMT (ARIS) (n=13)
      exercise program. AT consisted of bike exercise at 70-80% of max heart rate. ARIS
      training consisted of AT with RT of the quadriceps at 50% of 1 repetition maximum
      (1RM) and upper limb exercises using dumbbells of 1-2 kg as well as IMT at 60% of
      sustained maximal inspiratory pressure (SPI(max)). At baseline and after
      intervention patients underwent cardiopulmonary exercise testing,
      echocardiography, evaluation of dyspnea, muscle function and quality of life
      (QoL) scores. RESULTS: The ARIS program as compared to AT alone, resulted in
      additional improvement in quadriceps muscle strength (1RM, p=0.005) and endurance
      (50%1 RM * number of max repetitions, p=0.01), SPI(max) (p<0.001), exercise time
      (p=0.01), circulatory power (peak oxygen consumption * peak systolic blood
      pressure, p=0.05), dyspnea (p=0.03) and QoL (p=0.03). CONCLUSIONS: ARIS training
      was safe and resulted in incremental benefits in both peripheral and respiratory
      muscle weakness, cardiopulmonary function and QoL compared to that of AT. The
      present findings may add a new prospective to cardiac rehabilitation programs of
      heart failure patients whilst the clinical significance of these outcomes need to
      be addressed in larger randomised studies.

PMID- 22658572
TI  - Short term effect of CRT on biomarkers of cardiac remodelling and fibrosis: NT
      proBNP, sST2, galectin-3, and a marker of oxidative stress--ceruloplasmin--a
      pilot study.

PMID- 22658573
TI  - Left ventricular non-noncompaction: the mitral valve prolapse of the 21st
      century?
AB  - A spongiform epidemic is upon us - myocardial trabeculae are everywhere as left
      ventricular noncompaction (LVNC) ingratiates itself into modern day cardiology.
      Current understanding of the condition is evolving but remains incomplete, and
      brings to mind the chronicles of another great cardiac story: mitral valve
      prolapse. Anecdote suggests that many individuals with prominent trabeculae may
      be being falsely labelled with a disease - LVNC - using poor echocardiographic
      and cardiovascular magnetic resonance criteria. Until we have robust diagnostic
      criteria, aetiology, clinicopathological significance and prognosis, the risk of
      casualties from ascertainment bias will remain. We should look to history and
      learn from past mistakes - specifically from the mitral valve prolapse story to
      show the way forward for LVNC. Meanwhile, clinicians (and patients) should be
      wary, bearing in mind the possibility that they might be seeing LVNNC - left
      ventricular non-noncompaction.

PMID- 22658575
TI  - Ticagrelor in clopidogrel-resistant patients undergoing maintenance hemodialysis.

PMID- 22658576
TI  - Assessing sound exposure from shipping in coastal waters using a single
      hydrophone and Automatic Identification System (AIS) data.
AB  - Underwater noise from shipping is a growing presence throughout the world's
      oceans, and may be subjecting marine fauna to chronic noise exposure with
      potentially severe long-term consequences. The coincidence of dense shipping
      activity and sensitive marine ecosystems in coastal environments is of particular
      concern, and noise assessment methodologies which describe the high temporal
      variability of sound exposure in these areas are needed. We present a method of
      characterising sound exposure from shipping using continuous passive acoustic
      monitoring combined with Automatic Identification System (AIS) shipping data. The
      method is applied to data recorded in Falmouth Bay, UK. Absolute and relative
      levels of intermittent ship noise contributions to the 24-h sound exposure level
      are determined using an adaptive threshold, and the spatial distribution of
      potential ship sources is then analysed using AIS data. This technique can be
      used to prioritize shipping noise mitigation strategies in coastal marine
      environments.

PMID- 22658577
TI  - Environmentally safe areas and routes in the Baltic proper using Eulerian
      tracers.
AB  - In recent years, the shipping of environmentally hazardous cargo has increased
      considerably in the Baltic proper. In this study, a large number of hypothetical
      oil spills with an idealized, passive tracer are simulated. From the tracer
      distributions, statistical measures are calculated to optimize the quantity of
      tracer from a spill that would stay at sea as long as possible. Increased time
      may permit action to be taken against the spill before the oil reaches
      environmentally vulnerable coastal zones. The statistical measures are used to
      calculate maritime routes with maximum probability that an oil spill will stay at
      sea as long as possible. Under these assumptions, ships should follow routes that
      are located south of Bornholm instead of the northern routes in use currently.
      Our results suggest that the location of the optimal maritime routes depends on
      the season, although interannual variability is too large to identify
      statistically significant changes.

PMID- 22658578
TI  - Anti-class II -DR humanized monoclonal antibody, IMMU-114, blocks allogeneic
      immune response.
AB  - BACKGROUND: The effect of a humanized anti-human leukocyte antigen-DR monoclonal
      antibody, IMMU-114, on the allogeneic immune response was investigated in vitro.
      METHODS: Responder peripheral blood mononuclear cells were cocultured with
      inactivated self or allogeneic stimulator peripheral blood mononuclear cells in
      the presence of control antibody or IMMU-114. Thymidine incorporation rates were
      then measured. Phenotypic changes in peripheral blood mononuclear cells and the
      intracellular Th1-type cytokines interleukin-2, interferon-gamma, and tumor
      necrosis factor-alpha were analyzed using flow cytometry. The concentrations of
      interleukin-2, interferon-gamma, and tumor necrosis factor-alpha in the mixed
      lymphocyte reaction culture medium were measured. RESULTS: Thymidine
      incorporation rates at a 1:1 responder/stimulator ratio of allogeneic, allogeneic
      + IMMU-114, self, and self + IMMU-114 were 22,080.7 +/- 602.4, 2,254.5 +/- 118.1,
      1,284.0 +/- 227.8, and 494.5 +/- 27.5 cpm, respectively (P = .038). IMMU-114
      decreased the frequencies of human leukocyte antigen-DR-expressing CD16+56+ NK
      cells, CD19+ B cells, and CD3+25+ activated T cells. CONCLUSION: Intracellular
      cytokine assay and measurement of Th1-type cytokines in the mixed lymphocyte
      reaction culture medium revealed that IMMU-114 significantly decreased the titers
      of interleukin-2, interferon-gamma, and tumor necrosis factor-alpha. IMMU-114
      significantly suppresses the allogeneic immune response in vitro, partly through
      inhibition of the Th1 response.

PMID- 22658574
TI  - Estimating GFR among participants in the Chronic Renal Insufficiency Cohort
      (CRIC) Study.
AB  - BACKGROUND: Glomerular filtration rate (GFR) is considered the best measure of
      kidney function, but repeated assessment is not feasible in most research
      studies. STUDY DESIGN: Cross-sectional study of 1,433 participants in the Chronic
      Renal Insufficiency Cohort (CRIC) Study (ie, the GFR subcohort) to derive an
      internal GFR estimating equation using a split-sample approach. SETTING &
      PARTICIPANTS: Adults from 7 US metropolitan areas with mild to moderate chronic
      kidney disease; 48% had diabetes and 37% were black. INDEX TEST: CRIC GFR
      estimating equation. REFERENCE TEST OR OUTCOME: Urinary (125)I-iothalamate
      clearance testing (measured GFR [mGFR]). OTHER MEASUREMENTS: Laboratory measures,
      including serum creatinine and cystatin C, and anthropometrics. RESULTS: In the
      validation data set, the model that included serum creatinine level, serum
      cystatin C level, age, sex, and race was the most parsimonious and similarly
      predictive of mGFR compared with a model additionally including bioelectrical
      impedance analysis phase angle, CRIC clinical center, and 24-hour urinary
      creatinine excretion. Specifically, root mean square errors for the separate
      models were 0.207 versus 0.202, respectively. Performance of the CRIC GFR
      estimating equation was most accurate for the subgroups of younger participants,
      men, nonblacks, non-Hispanics, those without diabetes, those with body mass index
      <30 kg/m(2), those with higher 24-hour urine creatinine excretion, those with
      lower high-sensitivity C-reactive protein levels, and those with higher mGFRs.
      LIMITATIONS: Urinary clearance of (125)I-iothalamate is an imperfect measure of
      true GFR; cystatin C level is not standardized to certified reference material;
      lack of external validation; small sample sizes limit analyses of subgroup
      specific predictors. CONCLUSIONS: The CRIC GFR estimating equation predicts mGFR
      accurately in the CRIC cohort using serum creatinine and cystatin C levels, age,
      sex, and race. Its performance was best in younger and healthier participants.

PMID- 22658579
TI  - Self-reported segregation experience throughout the life course and its
      association with adequate health literacy.
AB  - Residential segregation has been shown to be associated with health outcomes and
      health care utilization. We examined the association between racial composition
      of five physical environments throughout the life course and adequate health
      literacy among 836 community health center patients in Suffolk County, NY.
      Respondents who attended a mostly White junior high school or currently lived in
      a mostly White neighborhood were more likely to have adequate health literacy
      compared to those educated or living in predominantly minority or diverse
      environments. This association was independent of the respondent's race,
      ethnicity, age, education, and country of birth.

PMID- 22658580
TI  - Serum levels of marine-derived n-3 fatty acids in Icelanders, Japanese, Koreans,
      and Americans--a descriptive epidemiologic study.
AB  - In the 1990s Iceland and Japan were known as countries with high fish consumption
      whereas coronary heart disease (CHD) mortality in Iceland was high and that in
      Japan was low among developed countries. We described recent data fish
      consumption and CHD mortality from publicly available data. We also measured CHD
      risk factors and serum levels of marine-derived n-3 and other fatty acids from
      population-based samples of 1324 men in Iceland, Japan, South Korea, and the US.
      CHD mortality in men in Iceland was almost 3 times as high as that in Japan and
      South Korea. Generally, a profile of CHD risk factors in Icelanders compared to
      Japanese was more favorable. Serum marine-derived n-3 fatty acids in Iceland were
      significantly lower than in Japan and South Korea but significantly higher than
      in the US.

PMID- 22658581
TI  - Unmet need for treatment for substance use disorders across race and ethnicity.
AB  - BACKGROUND: The objective was to analyze disparities in unmet need for substance
      use treatment and to observe variation across different definitions of need for
      treatment. METHODS: Data were analyzed from the 2002 to 2005 National Survey of
      Drug Use and Health and the National Epidemiologic Survey on Alcohol and Related
      Conditions. Logistic regressions estimated the likelihood of specialty substance
      use treatment across the two data sets. Parallel variables for specialty,
      informal and any substance abuse treatment were created. Perceived need and
      normative need for substance use treatment were defined, with normative need
      stratified across lifetime disorder, past twelve month disorder, and heavy
      alcohol/any illicit drug use. Treatment rates were analyzed, comparing Blacks,
      Asians and Latinos to non-Latino whites across need definitions, and adjusting
      for age, sex, household income, marital status, education and insurance. RESULTS:
      Asians with past year substance use disorder had a higher likelihood of unmet
      need for specialty treatment than whites. Blacks with past year disorder and with
      heavy drinking/illicit drug use had significantly lower likelihood of unmet need.
      Latinos with past year disorder had a higher likelihood of unmet need for
      specialty substance abuse treatment. Asians with heavy drinking/illicit drug use
      had lower likelihood of unmet need. CONCLUSIONS: The findings suggest that
      pathways to substance abuse treatment differ across groups. Given high rates of
      unmet need, a broad approach to defining need for treatment is warranted. Future
      research to disentangle social and systemic factors from factors based on
      diagnostic criteria is necessary in the identification of need for treatment.

PMID- 22658582
TI  - Identity exploration in the dating domain: the role of attachment dimensions and
      parenting practices.
AB  - We examined relations among perceived parenting practices (support and
      psychological control), attachment dimensions for romantic relationships (anxiety
      and avoidance) and exploration of the dating identity among actively dating
      adolescents in two high school aged samples. In the all female sample of Study 1
      (n = 653) and the gender balanced sample of Study 2 (n = 1003), parenting
      practices contributed to adolescent exploration of the dating identity. Parent
      psychological control, but not parental support, also contributed to elevated
      feeling of avoidance and anxiety in romantic relationships. Avoidance, in turn,
      was related to less exploration of the dating identity while anxiety seemed to
      increase it. Gender moderated the model, with parenting practices predicting
      exploration only for girls and with the links for avoidance and anxiety with
      exploration stronger for boys than girls. Indirect effects for parenting
      practices through attachment dimensions on exploration of the dating identity
      were also noted.

PMID- 22658583
TI  - [Prescription of systemic cold and cough drugs to children 0-13 years old. An
      unresolved problem].
AB  - INTRODUCTION AND OBJECTIVES: Upper respiratory tract infections are the most
      common cause of paediatric consultation, generating a high volume of
      prescriptions of drugs with unfavourable risk-benefit ratio. The aim of this
      study is to describe the prescription of systemic cough and cold medicines to
      children under 14 years of age in Castilla y Leon and analyse its variability.
      POPULATION AND METHODS: A count was made of the prescriptions for the R05
      therapeutic subgroup (antitussives and mucolytics) and the R01B pharmacological
      therapeutic subgroup (nasal decongestants for systemic use), prescribed for
      children under the age of 14 in the Public Health System between 2005-2010. The
      number of prescriptions was analysed as crude and age-adjusted rates, as well as
      a a multivariate analysis (Poisson regression) of the variability associated with
      health area, the urban/rural environment, age, and year of prescription. RESULTS:
      There were 806,785 prescriptions for systemic cough and cold drugs given to an
      exposed population of 1,580,229 person-years. Prescription rates (per 100 person
      years) were 20.7 (antitussives), 7.0 (sympathomimetic) and 23.4 (mucolytics).
      These drugs were employed more often in children <4 years. The prescription of
      mucolytics and sympathomimetics was highest at age of 1 year (rates=41.9 and
      18.7, respectively) and of antitussives at 3 years (35.7). Multivariate analysis
      showed that in rural areas the prescription was higher than in urban areas, and
      that there were also significant differences between health areas. CONCLUSIONS:
      Between 2005 and 2010 there was a high prescription of systemic cough and cold
      medicines, especially in children under 2 years old, and often outside the
      recommended conditions of use, and there was a high geographic variabilty.

PMID- 22658584
TI  - [Opened dorsal metacarpophalangeal dislocation of the four long fingers. Volar
      plates reinsertion with anchors].
AB  - The authors describe the case of a 53 year-old right-handed patient, who fell
      from a scaffolding and sustained a dorsal metacarpophalangeal dislocation of the
      four long fingers of his left hand. Because of the major dorsal instability after
      reduction, a mini anchor was placed over each metacarpal neck, to help repair the
      volar plate. After active rehabilitation, the patient regained satisfying
      articular amplitudes and was able to get back to his job and his regular sports
      activities.

PMID- 22658585
TI  - [Continuous infusion of ropivacaine has no effects on pyrolytic implant: a
      preliminary study in rats].
AB  - The aim of the study is to analyse the effects of ropivacaine on a pyrolytic
      implant in bone surgery. Ten rats were operated with a pyrolytic implant placed
      at the hip after femoral head resection: five cases with continuous infusion of
      ropivacaine and five cases with continuous infusion of sterile water. Six days
      after, all the implants were analysed: weight, length, width, thickness and
      global design. This work showed that ropivacaine can be use as continuous
      infusion with pyrolytic implant. Other studies in human surgery are necessary.

PMID- 22658586
TI  - [Freon gas frostbite: an unusual burn evolving in two stages].
AB  - Freon gas is a halogenated derivative widely used in refrigeration and air
      conditioning. It is maintained at a temperature below -41 degrees C and its
      contact with skin may cause very serious burns. This is usually an accident at
      work and the burns affect the hands of patients first. Unfortunately, early
      clinical presentation is often reassuring and does not reflect the actual depth
      of the injury. Few cases of this injury are reported and no treatment protocol is
      established at this time. We present two cases of frostbite by freon gas,
      initially evaluated at a stage of superficial burns and evolved spontaneously in
      a few days to full thickness burns necessitating surgical treatment by excision
      and skin grafting. This evolution in two phases has never been described and
      could help to better understand the pathophysiology of this frostbite and the
      possibilities of management.

PMID- 22658587
TI  - Affect-regulated exercise intensity: does training at an intensity that feels
      'good' improve physical health?
AB  - OBJECTIVES: Affect-regulated exercise to feel 'good' can be used to control
      exercise intensity amongst both active and sedentary individuals and should
      support exercise adherence. It is not known, however, whether affect-regulated
      exercise training can lead to physical health gains. The aim of this study was to
      examine if affect-regulated exercise to feel 'good' leads to improved fitness
      over the course of an 8-week training programme. DESIGN: A repeated measures
      design (pretest-posttest) with independent groups (training and control).
      METHODS: 20 sedentary females completed a submaximal graded exercise test and
      were then allocated to either a training group or control group. The training
      group completed two supervised sessions and one unsupervised session per week for
      8 weeks. Exercise intensity was affect-regulated to feel 'good'. Following the 8
      weeks of training, both groups completed a second submaximal graded exercise
      test. RESULTS: Repeated measures analyses of variance indicated a significant
      increase in the time to reach ventilatory threshold in the training group (318 +/
      23.7s) compared to control (248 +/- 16.9s). Overall compliance to training was
      high (>92%). Participants in the training group exercised at intensities that
      would be classified as being in the lower range of the recommended guidelines (~
      50% VO(2) max) for cardiovascular health. CONCLUSIONS: Affect-regulated exercise
      to feel 'good' can be used in a training programme to regulate exercise
      intensity. This approach led to a 19% increase in time to reach ventilatory
      threshold, which is indicative of improved fitness.

PMID- 22658588
TI  - Coinciding exercise with peak serum caffeine does not improve cycling
      performance.
AB  - OBJECTIVES: To investigate whether coinciding peak serum caffeine concentration
      with the onset of exercise enhances subsequent endurance performance. DESIGN:
      Randomised, double-blind, crossover. METHODS: In this randomised, placebo
      controlled, double-blind crossover study, 14 male trained cyclists and
      triathletes (age 31+/-5year, body mass 75.4+/-5.7 kg, VO2max 69.5+/-6.1 mL kg-1
      min-1 and peak power output 417+/-35W, mean+/-SD) consumed 6 mg kg(-1) caffeine
      or a placebo either 1h (C(1h)) prior to completing a 40 km time trial or when the
      start of exercise coincided with individual peak serum caffeine concentrations
      (C(peak)). C(peak) was determined from a separate 'caffeine profiling' session
      that involved monitoring caffeine concentrations in the blood every 30 min over a
      4h period. RESULTS: Following caffeine ingestion, peak serum caffeine occurred
      120 min in 12 participants and 150 min in 2 participants. Time to complete the 40
      km time trial was significantly faster (2.0%; p=0.002) in C(1h) compared to
      placebo. No statistically significant improvement in performance was noted in the
      C(peak) trial versus placebo (1.1%; p=0.240). Whilst no differences in metabolic
      markers were found between C(peak) and placebo conditions, plasma concentrations
      of glucose (p=0.005), norepinephrine and epinephrine (p<=0.002) were higher in
      the C(1h) trial 6 min post-exercise versus placebo. CONCLUSIONS: In contrast to
      coinciding peak serum caffeine concentration with exercise onset, caffeine
      consumed 60 min prior to exercise resulted in significant improvements in 40 km
      time trial performance. The ergogenic effect of caffeine was not found to be
      related to peak caffeine concentration in the blood at the onset of endurance
      exercise.

PMID- 22658589
TI  - Kinetic chain influences on upper and lower trapezius muscle activation during
      eight variations of a scapular retraction exercise in overhead athletes.
AB  - OBJECTIVES: To describe and compare the activation levels of the upper and lower
      trapezius muscle and study the influence of trunk and lower extremity position or
      movement during eight variations of a scapular retraction exercise. DESIGN:
      Descriptive study. Exercise performance was standardized and individualized based
      on height, age and body weight. METHODS: Individual muscle activation was
      captured by surface electromyography in thirty young healthy overhead athletes.
      Exercises were performed in front of a pulley apparatus. RESULTS: The mean values
      for upper trapezius and lower trapezius were 6.59% and 15.93% of maximum
      voluntary isometric contractions respectively. Main effects were found for
      "exercise" (F=2.60; p=0.037) and "muscle part" (F=25.44; p<0.001) in an ANOVA for
      repeated measures model showing higher lower trapezius muscle activation compared
      to the upper trapezius across exercises. An unipodal squat position on the
      contralateral leg increased trapezius muscle activation by 3.93% maximum
      voluntary isometric contraction (p=0.019) compared to the conventional seated
      performance of the exercise. No differences between phases were found and no
      exercise activated a particular muscle part (upper trapezius or lower trapezius)
      to a greater extent in comparison with other exercises since no two-way
      interactions were found with p<0.05. CONCLUSIONS: All exercise variations may be
      useful in the early phases of scapular rehabilitation training because of their
      favorable trapezius muscle balance activation. Standing in a squat position on
      the contralateral leg can result in a slight increase in trapezius muscle
      activation. However, future comparative effectiveness studies are needed to
      identify the long-term training benefits of these exercises.

PMID- 22658590
TI  - Optic atrophy 1-dependent mitochondrial remodeling controls steroidogenesis in
      trophoblasts.
AB  - During human pregnancy, placental trophoblasts differentiate and syncytialize
      into syncytiotrophoblasts that sustain progesterone production [1]. This process
      is accompanied by mitochondrial fragmentation and cristae remodeling [2], two
      facets of mitochondrial apoptosis, whose molecular mechanisms and functional
      consequences on steroidogenesis are unclear. Here we show that the mitochondria
      shaping protein Optic atrophy 1 (Opa1) controls efficiency of steroidogenesis.
      During syncytialization of trophoblast BeWo cells, levels of the profission
      mitochondria-shaping protein Drp1 increase, and those of Opa1 and mitofusin (Mfn)
      decrease, leading to mitochondrial fragmentation and cristae remodeling.
      Manipulation of the levels of Opa1 reveal an inverse relationship with the
      efficiency of steroidogenesis in trophoblasts and in mouse embryonic fibroblasts
      where the mitochondrial steroidogenetic pathway has been engineered. In an in
      vitro assay, accumulation of cholesterol is facilitated in the inner membrane of
      isolated mitochondria lacking Opa1. Thus, Opa1-dependent inner membrane
      remodeling controls efficiency of steroidogenesis.

PMID- 22658591
TI  - Positive feedback and mutual antagonism combine to polarize Crumbs in the
      Drosophila follicle cell epithelium.
AB  - Epithelial tissues are composed of polarized cells with distinct apical and
      basolateral membrane domains. In the Drosophila ovarian follicle cell epithelium,
      apical membranes are specified by Crumbs (Crb), Stardust (Sdt), and the aPKC-Par6
      cdc42 complex. Basolateral membranes are specified by Lethal giant larvae (Lgl),
      Discs large (Dlg), and Scribble (Scrib). Apical and basolateral determinants are
      known to act in a mutually antagonistic fashion, but it remains unclear how this
      interaction generates polarity. We have built a computer model of apicobasal
      polarity that suggests that the combination of positive feedback among apical
      determinants plus mutual antagonism between apical and basal determinants is
      essential for polarization. In agreement with this model, in vivo experiments
      define a positive feedback loop in which Crb self-recruits via Crb-Crb
      extracellular domain interactions, recruitment of Sdt-aPKC-Par6-cdc42, aPKC
      phosphorylation of Crb, and recruitment of Expanded (Ex) and Kibra (Kib) to
      prevent endocytic removal of Crb from the plasma membrane. Lgl antagonizes the
      operation of this feedback loop, explaining why apical determinants do not
      normally spread into the basolateral domain. Once Crb is removed from the plasma
      membrane, it undergoes recycling via Rab11 endosomes. Our results provide a
      dynamic model for understanding how epithelial polarity is maintained in
      Drosophila follicle cells.

PMID- 22658593
TI  - Hypertrophy and unconventional cell division of hepatocytes underlie liver
      regeneration.
AB  - BACKGROUND: The size of organs and tissues is basically determined by the number
      and size of their cells. However, little attention has been paid to this
      fundamental concept. The liver has a remarkable ability to regenerate after
      surgical resection (partial hepatectomy [PHx]), and hepatocytes account for about
      80% of liver weight, so we investigate how the number and size of hepatocytes
      contribute to liver regeneration in mice. It has been generally accepted that
      hepatocytes undergo one or two rounds of cell division after 70% PHx. However,
      ploidy of hepatocytes is known to increase during regeneration, suggesting an
      unconventional cell cycle. We therefore examine cell cycle of hepatocytes in
      detail. RESULTS: By developing a method for genetic fate mapping and a high
      throughput imaging system of individual hepatocytes, we show that cellular
      hypertrophy makes the first contribution to liver regeneration; i.e.,
      regeneration after 30% PHx is achieved solely by hypertrophy without cell
      division, and hypertrophy precedes proliferation after 70% PHx. Proliferation and
      hypertrophy almost equally contribute to regeneration after 70% PHx. Furthermore,
      although most hepatocytes enter cell cycle after 70% PHx, not all hepatocytes
      undergo cell division. In addition, binuclear hepatocytes undergo reductive
      divisions to generate two mononuclear daughter hepatocytes in some cases.
      CONCLUSIONS: Our findings demonstrate the importance of hypertrophy and the
      unconventional cell division cycle of hepatocytes in regeneration, prompting a
      significant revision of the generally accepted model of liver regeneration.

PMID- 22658592
TI  - Posttranslational acetylation of alpha-tubulin constrains protofilament number in
      native microtubules.
AB  - BACKGROUND: Microtubules are built from linear polymers of alpha-beta tubulin
      dimers (protofilaments) that form a tubular quinary structure. Microtubules
      assembled from purified tubulin in vitro contain between 10 and 16
      protofilaments; however, such structural polymorphisms are not found in cells.
      This discrepancy implies that factors other than tubulin constrain microtubule
      protofilament number, but the nature of these constraints is unknown. RESULTS:
      Here, we show that acetylation of MEC-12 alpha-tubulin constrains protofilament
      number in C. elegans touch receptor neurons (TRNs). Whereas the sensory dendrite
      of wild-type TRNs is packed with a cross-linked bundle of long, 15-protofilament
      microtubules, mec-17;atat-2 mutants lacking alpha-tubulin acetyltransferase
      activity have short microtubules, rampant lattice defects, and variable
      protofilament number both between and within microtubules. All-atom molecular
      dynamics simulations suggest a model in which acetylation of lysine 40 promotes
      the formation of interprotofilament salt bridges, stabilizing lateral
      interactions between protofilaments and constraining quinary structure to produce
      stable, structurally uniform microtubules in vivo. CONCLUSIONS: Acetylation of
      alpha-tubulin is an essential constraint on protofilament number in vivo. We
      propose a structural model in which this posttranslational modification promotes
      the formation of lateral salt bridges that fine-tune the association between
      adjacent protofilaments and enable the formation of uniform microtubule
      populations in vivo.

PMID- 22658594
TI  - Live imaging of tumor initiation in zebrafish larvae reveals a trophic role for
      leukocyte-derived PGE2.
AB  - Epidemiology studies and clinical trials have suggested that the use of non
      steroidal anti-inflammatory drugs (NSAIDs), including aspirin, can significantly
      reduce the incidence of and mortality associated with many cancers, and
      upregulation of the COX2-PGE(2) pathway in tumor microenvironments might drive
      several aspects of cancer progression. For these reasons, the mechanisms linking
      COX blockade and cancer prevention have long been an area of active
      investigation. During carcinogenesis, COX-2 is expressed both by malignant
      epithelial cells and by tumor-associated stromal cells, including macrophages,
      but the observation that NSAIDs are most effective in cancer prevention in
      APC(min/+) mice if the mice are treated from conception suggests that the COX
      2/PGE(2) pathway might also be critical at the earliest stages of tumor
      development. In this study we take advantage of the translucency and genetic
      tractability of zebrafish larvae to investigate the involvement of inflammatory
      cells at cancer initiation, when transformed cells first arise in tissues. We
      previously showed that innate immune cells supply early transformed cells with
      proliferative cues and, by using complementary pharmacological and genetic
      experiments, we now show that prostaglandin E(2) (PGE(2)) is the trophic signal
      required for this expansion of transformed cells. Our in vivo observations at
      these early stages of cancer initiation provide a potential mechanistic
      explanation for why long-term use of low doses of NSAIDs, including aspirin,
      might reduce cancer onset.

PMID- 22658595
TI  - Distinct traces for appetitive versus aversive olfactory memories in DPM neurons
      of Drosophila.
AB  - The global logic used by the brain for differentially encoding positive and
      negative experiences remains unknown along with how such experiences are
      represented by collections of memory traces at the cellular level. Here we
      contrast the cellular memory traces that form in the dorsal paired medial (DPM)
      neurons of Drosophila after conditioning flies with odors associated with
      aversive or appetitive unconditioned stimuli (US). Our results show that the
      appetitive DPM neuron trace is distinguished from the aversive in three
      fundamental ways: (1) The DPM neurons do not respond to an appetitive US of
      sucrose by itself, in contrast to their robust response to an aversive US. (2)
      The appetitive trace persists for twice as long as the aversive trace. (3) The
      appetitive trace is expressed in both neurite branches of the neuron, rather than
      being confined to a single branch like the aversive trace. In addition, we
      demonstrate that training flies with nonnutritive sugars that elicit a behavioral
      memory that decays within 24 hr generates, like aversive conditioning, a short
      lived and branch-restricted memory trace. These results indicate that the
      persistence and breadth of the DPM neuron memory trace influences the duration of
      behavioral memory.

PMID- 22658596
TI  - Birth of new spliceosomal introns in fungi by multiplication of introner-like
      elements.
AB  - Spliceosomal introns are noncoding sequences that separate exons in eukaryotic
      genes and are removed from pre-messenger RNAs by the splicing machinery. Their
      origin has remained a mystery in biology since their discovery because intron
      gains seem to be infrequent in many eukaryotic lineages. Although a few recent
      intron gains have been reported, none of the proposed gain mechanisms can
      convincingly explain the high number of introns in present-day eukaryotic
      genomes. Here we report on particular spliceosomal introns that share high
      sequence similarity and are reminiscent of introner elements. These elements
      multiplied in unrelated genes of six fungal genomes and account for the vast
      majority of intron gains in these fungal species. Such introner-like elements
      (ILEs) contain all typical characteristics of regular spliceosomal introns (RSIs)
      but are longer and predicted to harbor more stable secondary structures. However,
      dating of multiplication events showed that they degenerate in sequence and
      length within 100,000 years to eventually become indistinguishable from RSIs. We
      suggest that ILEs not only account for intron gains in six fungi but also in
      ancestral eukaryotes to give rise to most RSIs by a yet unknown multiplication
      mechanism.

PMID- 22658597
TI  - The nuclear receptor unfulfilled is required for free-running clocks in
      Drosophila pacemaker neurons.
AB  - An intricate neural circuit composed of multiple classes of clock neurons
      controls circadian locomotor rhythms in Drosophila. Evidence indicates that the
      small ventral lateral neurons (s-LNvs, M cells) are the dominant pacemaker
      neurons that synchronize the clocks throughout the circuit and drive free-running
      locomotor rhythms. Little is known, however, about the molecular underpinning of
      this unique function of the s-LNvs. Here, we show that the nuclear receptor gene
      unfulfilled (unf; DHR51) is required for the function of the s-LNvs. UNFULFILLED
      (UNF) is rhythmically expressed in the s-LNvs, and unf mutant flies are
      behaviorally arrhythmic. Knockdown of unf in developing LNvs irreversibly
      destroys the ability of adult s-LNvs to generate free-running rhythms, whereas
      depletion of UNF from adult LNvs dampens the rhythms of the s-LNvs only in
      constant darkness. These temporally controlled LNv-targeted unf knockdowns
      desynchronize circuit-wide molecular rhythms and disrupt behavioral rhythms.
      Therefore, UNF is a prerequisite for free-running clocks in the s-LNvs and for
      the function of the entire circadian circuit.

PMID- 22658598
TI  - Neural circuitry underlying Drosophila female postmating behavioral responses.
AB  - BACKGROUND: After mating, Drosophila females undergo a remarkable phenotypic
      switch resulting in decreased sexual receptivity and increased egg laying.
      Transfer of male sex peptide (SP) during copulation mediates these postmating
      responses via sensory neurons that coexpress the sex-determination gene fruitless
      (fru) and the proprioceptive neuronal marker pickpocket (ppk) in the female
      reproductive system. Little is known about the neuronal pathways involved in
      relaying SP-sensory information to central circuits and how these inputs are
      processed to direct female-specific changes that occur in response to mating.
      RESULTS: We demonstrate an essential role played by neurons expressing the sex
      determination gene doublesex (dsx) in regulating the female postmating response.
      We uncovered shared circuitry between dsx and a subset of the previously
      described SP-responsive fru(+)/ppk(+)-expressing neurons in the reproductive
      system. In addition, we identified sexually dimorphic dsx circuitry within the
      abdominal ganglion (Abg) critical for mediating postmating responses. Some of
      these dsx neurons target posterior regions of the brain while others project onto
      the uterus. CONCLUSIONS: We propose that dsx-specified circuitry is required to
      induce female postmating behavioral responses, from sensing SP to conveying this
      signal to higher-order circuits for processing and through to the generation of
      postmating behavioral and physiological outputs.

PMID- 22658599
TI  - The neural correlates of crowding-induced changes in appearance.
AB  - Object recognition in the peripheral visual field is limited by crowding: the
      disruptive influence of nearby clutter. Despite its severity, little is known
      about the cortical locus of crowding. Here, we examined the neural correlates of
      crowding by combining event-related fMRI adaptation with a change-detection
      paradigm. Crowding can change the appearance of objects, such that items become
      perceptually matched to surrounding objects; we used this change in appearance as
      a signature of crowding and measured brain activity that correlated with the
      crowded percept. Observers adapted to a peripheral patch of noise surrounded by
      four Gabor flankers. When crowded, the noise appears oriented and perceptually
      indistinguishable from the flankers. Consequently, substitution of the noise for
      a Gabor identical to the flankers ("change-same") is rarely detected, whereas
      substitution for an orthogonal Gabor ("change-different") is rarely missed. We
      predicted that brain areas representing the crowded percept would show repetition
      suppression in change-same trials but release from adaptation in change-different
      trials. This predicted pattern was observed throughout cortical visual areas V1
      V4, increasing in strength from early to late visual areas. These results depict
      crowding as a multistage process, involving even the earliest cortical visual
      areas, with perceptual consequences that are increasingly influenced by later
      visual areas.

PMID- 22658600
TI  - The budding yeast nuclear envelope adjacent to the nucleolus serves as a membrane
      sink during mitotic delay.
AB  - The mechanisms that dictate nuclear shape are largely unknown. Here we screened
      the budding yeast deletion collection for mutants with abnormal nuclear shape. A
      common phenotype was the appearance of a nuclear extension, particularly in
      mutants in DNA repair and chromosome segregation genes. Our data suggest that
      these mutations led to the abnormal nuclear morphology indirectly, by causing a
      checkpoint-induced cell-cycle delay. Indeed, delaying cells in mitosis by other
      means also led to the appearance of nuclear extensions, whereas inactivating the
      DNA damage checkpoint pathway in a DNA repair mutant reduced the fraction of
      cells with nuclear extensions. Formation of a nuclear extension was specific to a
      mitotic delay, because cells arrested in S or G2 had round nuclei. Moreover, the
      nuclear extension always coincided with the nucleolus, while the morphology of
      the DNA mass remained largely unchanged. Finally, we found that phospholipid
      synthesis continued unperturbed when cells delayed in mitosis, and inhibiting
      phospholipid synthesis abolished the formation of nuclear extensions. Our data
      suggest a mechanism that promotes nuclear envelope expansion during mitosis. When
      mitotic progression is delayed, cells sequester the added membrane to the nuclear
      envelope associated with the nucleolus, possibly to avoid disruption of
      intranuclear organization.

PMID- 22658601
TI  - Sleep fragmentation and motor restlessness in a Drosophila model of Restless Legs
      Syndrome.
AB  - Restless Legs Syndrome (RLS), first chronicled by Willis in 1672 and described in
      more detail by Ekbom in 1945, is a prevalent sensorimotor neurological disorder
      (5%-10% in the population) with a circadian predilection for the evening and
      night. Characteristic clinical features also include a compelling urge to move
      during periods of rest, relief with movement, involuntary movements in sleep
      (viz., periodic leg movements of sleep), and fragmented sleep. Although the
      pathophysiology of RLS is unknown, dopaminergic neurotransmission and deficits in
      iron availability modulate expressivity. Genome-wide association studies have
      identified a polymorphism in an intronic region of the BTBD9 gene on chromosome 6
      that confers substantial risk for RLS. Here, we report that loss of the
      Drosophila homolog CG1826 (dBTBD9) appreciably disrupts sleep with concomitant
      increases in waking and motor activity. We further show that BTBD9 regulates
      brain dopamine levels in flies and controls iron homeostasis through the iron
      regulatory protein-2 in human cell lines. To our knowledge, this represents the
      first reverse genetic analysis of a "novel" or heretofore poorly understood gene
      implicated in an exceedingly common and complex sleep disorder and the
      development of an RLS animal model that closely recapitulates all disease
      phenotypes.

PMID- 22658602
TI  - Genetically separable functions of the MEC-17 tubulin acetyltransferase affect
      microtubule organization.
AB  - BACKGROUND: Microtubules (MTs) are formed from the lateral association of 11-16
      protofilament chains of tubulin dimers, with most cells containing 13
      protofilament (13-p) MTs. How these different MTs are formed is unknown, although
      the number of protofilaments may depend on the nature of the alpha- and beta
      tubulins. RESULTS: Here we show that the enzymatic activity of the
      Caenorhabiditis elegans alpha-tubulin acetyltransferase (alpha-TAT) MEC-17 allows
      the production of 15-p MTs in the touch receptor neurons (TRNs) MTs. Without MEC
      17, MTs with between 11 and 15 protofilaments are seen. Loss of this enzymatic
      activity also changes the number and organization of the TRN MTs and affects TRN
      axonal morphology. In contrast, enzymatically inactive MEC-17 is sufficient for
      touch sensitivity and proper process outgrowth without correcting the MT defects.
      Thus, in addition to demonstrating that MEC-17 is required for MT structure and
      organization, our results suggest that the large number of 15-p MTs, normally
      found in the TRNs, is not essential for mechanosensation. CONCLUSION: These
      experiments reveal a specific role for alpha-TAT in the formation of MTs and in
      the production of higher order MTs arrays. In addition, our results indicate that
      the alpha-TAT protein has functions that require acetyltransferase activity (such
      as the determination of protofilament number) and others that do not (presence of
      internal MT structures).

PMID- 22658603
TI  - Cineradiography of monkey lip-smacking reveals putative precursors of speech
      dynamics.
AB  - A key feature of speech is its stereotypical 5 Hz rhythm. One theory posits that
      this rhythm evolved through the modification of rhythmic facial movements in
      ancestral primates. If the hypothesis has any validity, then a comparative
      approach may shed some light. We tested this idea by using cineradiography (X-ray
      movies) to characterize and quantify the internal dynamics of the macaque monkey
      vocal tract during lip-smacking (a rhythmic facial expression) versus chewing.
      Previous human studies showed that speech movements are faster than chewing
      movements, and the functional coordination between vocal tract structures is
      different between the two behaviors. If rhythmic speech evolved through a
      rhythmic ancestral facial movement, then one hypothesis is that monkey lip
      smacking versus chewing should also exhibit these differences. We found that the
      lips, tongue, and hyoid move with a speech-like 5 Hz rhythm during lip-smacking,
      but not during chewing. Most importantly, the functional coordination between
      these structures was distinct for each behavior. These data provide empirical
      support for the idea that the human speech rhythm evolved from the rhythmic
      facial expressions of ancestral primates.

PMID- 22658604
TI  - Pediatric airway abnormalities: evaluation and management.
AB  - Sleep disordered breathing syndromes in pediatric patients can lead to adverse
      effects in the cardiovascular system, neurocognitive function, growth, and
      behavior. These syndromes occur more frequently in patients with craniofacial
      disorders. A high index of suspicion as well as early recognition, detection, and
      treatment of these syndromes are considered integral to care of children with
      craniofacial disorders.

PMID- 22658605
TI  - E-cadherin in non-tumor epithelium adjacent to oral cancer as risk marker for the
      development of multiple tumors.
AB  - Our aim was to find out whether the loss of E-cadherin is a risk factor for the
      development of multiple tumours in the oral cavity and whether it could serve as
      a diagnostic marker for oral premalignant fields. We studied 77 oral squamous
      cell carcinomas (SCC) with associated non-tumour epithelia from 61 patients.
      Immunohistochemical studies (antibody NHC-38) were used to investigate E-cadherin
      expression, which was completely lost in basal (48% of cases) and parabasal (43%)
      layers of non-tumour epithelia close to the tumour and in basal (47%) and
      parabasal (38%) layers of non-tumour epithelia distant from the tumour. In
      multiple tumours E-cadherin expression was significantly lower than in single
      tumours in the basal, parabasal layers, and the middle third of close (p=0.002,
      <0.001, <0.001) and distant (p=0.041, p<0.001, p=0.005) non-tumour epithelia,
      respectively. Downregulation of E-cadherin may be valuable as a risk marker for
      the development of multiple tumours in the oral cavity and for the diagnosis of
      premalignant fields.

PMID- 22658606
TI  - Management of the temporomandibular joint in rheumatoid disorders.
AB  - This article summarises the rheumatoid diseases that particularly affect the
      temporomandibular joint (TMJ): psoriatic arthropathy, ankylosing spondylitis, and
      rheumatoid arthritis. Management is by a joint approach between rheumatologists
      and maxillofacial surgeons with a specific interest in diseases of the TMJ who
      give early surgical advice. Steroid injections, whilst useful in the short term,
      are not useful for long term or repeated treatment, and may lead to collapse of
      the joint and development of a deformed anterior open bite. These disorders
      should be managed primarily using standard conservative regimens, and failure to
      respond should lead to diagnostic or therapeutic arthroscopy and appropriate
      surgical treatment. When ankylosis develops or the joint collapses, a replacement
      joint should be considered and patients should be referred to an appropriately
      trained surgeon.

PMID- 22658607
TI  - Passive movement of human soft palate during respiration: A simulation of 3D
      fluid/structure interaction.
AB  - This study reconstructed a three dimensional fluid/structure interaction (FSI)
      model to investigate the compliance of human soft palate during calm respiration.
      Magnetic resonance imaging scans of a healthy male subject were obtained for
      model reconstruction of the upper airway and the soft palate. The fluid domain
      consists of nasal cavity, nasopharynx and oropharynx. The airflow in upper airway
      was assumed as laminar and incompressible. The soft palate was assumed as linear
      elastic. The interface between airway and soft palate was the FSI interface.
      Sinusoidal variation of velocity magnitude was applied at the oropharynx
      corresponding to ventilation rate of 7.5L/min. Simulations of fluid model in
      upper airway, FSI models with palatal Young's modulus of 7539Pa and 3000Pa were
      carried out for two cycles of respiration. The results showed that the integrated
      shear forces over the FSI interface were much smaller than integrated pressure
      forces in all the three directions (axial, coronal and sagittal). The total
      integrated force in sagittal direction was much smaller than that of coronal and
      axial directions. The soft palate was almost static during inspiration but moved
      towards the posterior pharyngeal wall during expiration. In conclusion, the
      displacement of human soft palate during respiration was mainly driven by air
      pressure around the surface of the soft palate with minimal contribution of shear
      stress of the upper airway flow. Despite inspirational negative pressure,
      expiratory posterior movement of soft palate could be another factor for the
      induction of airway collapse.

PMID- 22658608
TI  - Increased fatigability of the gastrocnemius medialis muscle in individuals with
      intermittent claudication.
AB  - BACKGROUND: We attempted to identify possible differences in the contractility of
      the gastrocnemius medialis (GM) muscle between healthy controls and individuals
      with peripheral arterial disease (PAD) and intermittent lower-limb claudication.
      METHODS: The GM muscles of 17 PAD patients and 17 healthy controls were examined
      with tensiomyography. Single or multiple electrical impulses were used to trigger
      muscle contractions, and the time and amplitude of contractions were measured.
      RESULTS: After single-impulse stimulation, the GM muscles of PAD patients showed
      significantly shorter contraction times (P < 0.001) than the GM muscles of
      controls. During 1 min of repetitive electrical stimulation, the contraction
      velocity of the controls' GM muscles typically showed a sustained increase
      throughout the stimulation period, whereas in PAD patients, a significant
      decrease in contraction velocity was observed after 30 s. The onset of muscle
      fatigue was unrelated to the ankle brachial index (ABI) of the examined leg. When
      the legs of PAD patients with higher and lower ABIs were compared to each other,
      no significant differences were found regarding the time and amplitude of
      contraction after single-impulse stimulation. CONCLUSIONS: The GM muscles of
      individuals with intermittent claudication contract more quickly and fatigue
      earlier than the GM muscles of healthy controls. Because the contraction time,
      measured with tensiomyography, reflects the individual's muscle fibre
      composition, our findings may reflect a shift from type I fibres to type II
      fibres in the GM muscles of PAD patients. Our data support the idea that calf
      myopathy is present in claudication-prone patients and, in part, determines the
      clinical manifestations of PAD.

PMID- 22658609
TI  - Low density lipoprotein receptor related protein 1 and abdominal aortic
      aneurysms.
AB  - OBJECTIVES: A recent GWAS demonstrated an association between low density
      lipoprotein receptor related protein 1 (LRP1) and abdominal aortic aneurysm
      (AAA). This review aims to identify how LRP1 may be involved in the pathogenesis
      of abdominal aortic aneurysm. DESIGN AND MATERIALS: A systematic review of the
      English language literature was undertaken in order to determine whether LRP1 and
      associated pathways were plausible candidates for contributing to the development
      and/or progression of AAA. METHODS AND RESULTS: A comprehensive literature search
      of MEDLINE (since 1948), Embase (since 1980) and Health and Psychological
      Instruments (since 1985) was conducted in January 2012 identified 50 relevant
      articles. These studies demonstrate that LRP1 has a diverse range of biological
      functions and is a plausible candidate for playing a central role in
      aneurysmogenesis. Importantly, LRP1 downregulates MMP (matrix metalloproteinase)
      activity in vascular smooth muscle cells and regulates other key pathways
      involved in extracellular matrix remodelling and vascular smooth muscle migration
      and proliferation. Crucially animal studies have shown that LRP1 depletion leads
      to progressive destruction of the vascular architecture and aneurysm formation.
      CONCLUSIONS: Published evidence suggests that LRP1 may play a key role in the
      development of AAA.

PMID- 22658610
TI  - Quantity of residual thrombus after successful catheter-directed thrombolysis for
      iliofemoral deep venous thrombosis correlates with recurrence.
AB  - OBJECTIVES: Iliofemoral deep venous thrombosis (IFDVT) is an independent risk
      factor for recurrent DVT. It has been observed that recurrent DVT correlates with
      residual thrombus. This study evaluates whether risk of recurrence is related to
      the amount of residual thrombus following catheter-directed thrombolysis (CDT)
      for IFDVT. METHODS: Patients who underwent CDT for IFDVT had their degree of
      lysis quantified by a reader blind to the patients' long-term clinical outcome.
      Patients were classified into two groups, >=50% and <50% residual thrombus.
      Recurrence was defined as a symptomatic presentation with image verification of
      new or additional thrombus. RESULTS: A total of 75 patients underwent CDT for
      IFDVT. Median follow-up was 35.9 months. Sixty-eight patients (91%) had no
      evidence of recurrence and seven (9%) developed recurrence. Of the patients who
      had >=50% (mean 80%) residual thrombus, 50% (4/8) experienced recurrence, but in
      those with <50% (mean 35%) residual thrombus, only 5% (3/67) had recurrent DVT (P
      = 0.0014). CONCLUSION: The burden of residual thrombus at completion of CDT
      correlates with the risk of DVT recurrence. Patients having CDT for IFDVT had a
      lower risk of recurrence than expected. Successful clearing of acute clot in
      IFDVT patients significantly reduces the recurrence risk compared to patients
      with a large residual thrombus burden.

PMID- 22658611
TI  - Commentary on 'general anaesthesia is associated with adverse cardiac outcome
      after endovascular aneurysm repair'.

PMID- 22658612
TI  - Lower limb revascularization with infragenicular bypass using PTFE graft and the
      distal vein patch technique: does it confer any advantage over the distal vein
      cuff techniques?

PMID- 22658613
TI  - International variations in infrainguinal bypass surgery - a VASCUNET report.
AB  - OBJECTIVES: To compare practice in lower limb bypass surgery in nine countries.
      DESIGN: A prospective study amalgamating and analysing data from national and
      regional vascular registries. METHODS: A table of data fields and definitions was
      agreed by all member countries of the Vascunet Collaboration. Data from January
      2005 to December 2009 was submitted to a central database. RESULTS: 32,084 cases
      of infrainguinal bypass (IIB) in nine countries were analysed. Procedures per
      100,000 population varied between 2.3 in the UK and 24.6 in Finland. The
      proportion of women varied from 25% to 43.5%. The median age for all countries
      was 70 for men and 76 for women. Hungary treated the youngest patients. IIB was
      performed for claudication for between 15.7% and 40.8% of all procedures. Vein
      grafts were used in patients operated on for claudication (52.9%), for rest pain
      (66.7%) and tissue loss (74.1%). Italy had the highest use of synthetic grafts.
      Among claudicants 45% of bypasses were performed to the below knee popliteal
      artery or more distally. Graft patency at 30 days varied between 86% and 99%.
      CONCLUSIONS: Significant variations in practice between countries were
      demonstrated. These results should be interpreted alongside the known limitations
      of such registry data with respect to quality and completeness of the data.
      Variation in data completeness and data validation between countries needs to be
      improved for useful international comparison of outcomes.

PMID- 22658614
TI  - Management of uncomplicated varicose veins - a case vignette for a clinical
      decision proposal.
AB  - Venous disorder is common in the general population. Uncomplicated varicose veins
      represent a significant proportion of the disease burden, and can impact
      considerably on quality of life, producing a wide spectrum of symptoms. Little is
      known about the natural course of the disease at this stage and the treatment
      strategy employed is often not based on robust scientific evidence. The aim of
      this article is to elucidate the options to manage uncomplicated varicose veins.
      There are likely to be significant geographic differences in the treatment
      strategy employed, and it is hoped that we will arouse discussion among
      physicians regarding the management of this very common medical condition. The
      reader will be asked for their preferred treatment choice for a given clinical
      case vignette.

PMID- 22658615
TI  - Regional disparities in incidence, handling and outcomes of patients with
      symptomatic and ruptured abdominal aortic aneurysms in Norway.
AB  - OBJECTIVES: To study incidence, handling and outcome of patients hospitalised
      with symptomatic and ruptured abdominal aortic aneurysm in Norway. DESIGN,
      MATERIAL AND METHODS: Retrospective study of 1291 patients, between January 2008
      and August 2010 using the National Patient Registry and a regional vascular
      surgery registry. We applied a stepwise logistic regression model to detect
      differences in regional in-hospital mortality. RESULTS: 385/711 (54%) patients
      hospitalised for aneurysm rupture, rAAA (ICD-10: I71.3), died. The odds of dying
      varied with a factor 2.3 between the extreme regions. 475/711 (67%) underwent
      repair, 323 survived, giving an in-hospital mortality rate of 32% after surgery.
      Older patients were significantly less likely to be transported for surgery. The
      overall incidence for patients aged >50 was 16.6 rAAA per 100,000 person-years.
      There was remarkable variation across counties with rates between 7.7 and 26.8. A
      total of 580 patients were hospitalised with suspected symptomatic aneurysms (ICD
      10:I71.4, acute admission); 224 (39%) were treated with aneurysm repair, 356
      (61%) were discharged without repair without a significant difference across
      health regions. CONCLUSIONS: For rAAA, we found substantial geographical
      variations in incidence, surgery and patient outcome. These results highlight the
      need for increased awareness about the condition and suggest ways to improve care
      trajectories to reduce delay to surgery, thereby minimising rupture mortality.

PMID- 22658616
TI  - The European Society for Vascular Surgery guidelines for carotid intervention: an
      updated independent assessment and literature review.
AB  - BACKGROUND AND PURPOSE: Many medical societies now recommend carotid stenting as
      an alternative to endarterectomy which raises the question of whether the ESVS
      guidelines are still valid. This review addresses the validity of the ESVS
      guidelines that refer to carotid stenting based on the evidence available today.
      METHODS: We conducted a review and meta-analysis based on the original ESVS
      guidelines paper and articles published over the past 2 years. RESULTS: For
      symptomatic patients, surgery remains the best option, since stenting is
      associated with a 61% relative risk increase of periprocedural stroke or death
      compared to endarterectomy. However, centres of excellence in carotid stenting
      may achieve comparable results. In asymptomatic patients, there is still no good
      evidence for any intervention because the stroke risk from an asymptomatic
      stenosis is very low, especially with the best modern medical treatment. CREST
      and CAVATAS have verified that mid-term stroke prevention after successful
      stenting is similar to endarterectomy. EVA-3S, SPACE, ICSS and CREST have
      provided additional evidence regarding the role of age in choosing therapeutic
      modality. The role of the cerebral protection devices is challenged by the
      imaging findings of small randomised trials but supported by large systematic
      reviews. CONCLUSIONS: The ESVS guidelines that refer to carotid stenting not only
      remain valid but also have been further strengthened by the latest available
      clinical data. An update of these guidelines including all of the recent evidence
      is needed to provide an objective and up-to-date interpretation of the data.

PMID- 22658617
TI  - The basilic vein and the cephalic vein perform equally in upper arm arteriovenous
      fistulae.
AB  - OBJECTIVE: To compare the brachiocephalic (BC) and basilic vein transposition
      (BVT) arteriovenous fistula (AVF) with regard to maturation, patency, blood flow
      and complication rates. DESIGN: A retrospective chart review. MATERIALS AND
      METHOD: Between January 2000 and December 2010, consecutive patients undergoing
      BC or BVT AVF were included. Patient characteristics were collected
      retrospectively from digital patient files and a prospective database of
      haemodialysis patients. RESULTS: A total of 173 autologous upper arm AVFs (87 BC
      and 86 BVT) were created in 151 patients. Mean (+/-SEM) follow-up was 19 +/- 1.4
      months (range 0-100). There were no differences between the groups in respect to
      brachial artery and cubital fossa vein diameters, time to first use, flow and the
      number of secondary interventions. Operative time was significantly longer (P <
      0.001) and the mid upper arm vein diameter before bifurcation greater (P = 0.038)
      in BVT patients. The 1- and 2-year primary patency rates for the whole cohort was
      40.8% and 30.2% with secondary patency rates of 78.0% and 72.4%. There was no
      difference between the groups for these outcomes (P = 0.951, P = 0.516,
      respectively). CONCLUSION: With the exception of the efferent vein diameter in
      the mid upper arm and operative time, there was no difference between a BC and
      BVT AVF.

PMID- 22658619
TI  - A simple adaptation method improved the interpretability of prediction models for
      composite end points.
AB  - OBJECTIVE: The pros and cons of composite end points in prognostic research are
      discussed, and an adaptation method, designed to accurately adjust absolute risks
      for a composite end point to risks for the individual component outcomes, is
      presented. STUDY DESIGN AND SETTING: An example prediction model for recurrent
      cardiovascular events (composite end point) was used to evaluate the performance
      regarding the individual component outcomes (cardiovascular death, myocardial
      infarction, and stroke) before and after the adaptation method. RESULTS:
      Discrimination for the individual component outcomes (concordance index for
      myocardial infarction, 0.68; concordance index for stroke, 0.70) was very similar
      to discrimination for the original composite end point (concordance index, 0.70).
      For cardiovascular death, it even increased substantially (concordance index,
      0.78). After adaptation, calibration plots for the component outcomes also
      improved, with visible convergence of the predicted risks and the observed
      incidences. CONCLUSION: In sum, these findings show that the adaptation method is
      useful when validating or applying a composite end point prediction model to the
      individual component outcomes. Following from this, recommendations concerning
      reporting of composite end points in future research are also included. Without
      the need for extra data, composite end point prediction models can easily be
      directly expanded to allow for the estimation of risk for each individual
      component outcome, improving the interpretability for clinicians and patients.

PMID- 22658618
TI  - ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis
      using massively parallel sequencing.
AB  - Lynch syndrome (hereditary nonpolyposis colon cancer) and adenomatous polyposis
      syndromes frequently have overlapping clinical features. Current approaches for
      molecular genetic testing are often stepwise, taking a best-candidate gene
      approach with testing of additional genes if initial results are negative. We
      report a comprehensive assay called ColoSeq that detects all classes of mutations
      in Lynch and polyposis syndrome genes using targeted capture and massively
      parallel next-generation sequencing on the Illumina HiSeq2000 instrument. In
      blinded specimens and colon cancer cell lines with defined mutations, ColoSeq
      correctly identified 28/28 (100%) pathogenic mutations in MLH1, MSH2, MSH6, PMS2,
      EPCAM, APC, and MUTYH, including single nucleotide variants (SNVs), small
      insertions and deletions, and large copy number variants. There was 100%
      reproducibility of detection mutation between independent runs. The assay
      correctly identified 222 of 224 heterozygous SNVs (99.4%) in HapMap samples,
      demonstrating high sensitivity of calling all variants across each captured gene.
      Average coverage was greater than 320 reads per base pair when the maximum of 96
      index samples with barcodes were pooled. In a specificity study of 19 control
      patients without cancer from different ethnic backgrounds, we did not find any
      pathogenic mutations but detected two variants of uncertain significance. ColoSeq
      offers a powerful, cost-effective means of genetic testing for Lynch and
      polyposis syndromes that eliminates the need for stepwise testing and multiple
      follow-up clinical visits.

PMID- 22658620
TI  - Public perception of "scarless" surgery: a critical analysis of the literature.
AB  - Evidence relating to the perception and view of patients and physicians on
      natural orifice transluminal endoscopic surgery (NOTES) and laparoendoscopic
      single-site surgery (LESS) was scrutinized. A comprehensive literature search was
      performed through PubMed. A total of 18 studies were included in the analysis.
      Patients demonstrated interest in scarless surgery, with a preference for LESS
      over NOTES. Safety and efficacy remain the key factors in the decision-making
      process of patients. With more information about the safety and reproducibility
      of LESS and NOTES, and with improved educational efforts, patients and physicians
      alike may feel more comfortable in widespread application of scarless surgery.

PMID- 22658621
TI  - The most reliable preoperative assessment of renal stone burden as a predictor of
      stone-free status after flexible ureteroscopy with holmium laser lithotripsy: a
      single-center experience.
AB  - OBJECTIVE: To examine which parameters should be measured to preoperatively
      determine the stone burden as predictors of stone-free (SF) status after a single
      flexible ureteroscopy (URS). Although several stone parameters reportedly
      influence the outcome of treatment for urinary stones, the most reliable
      indicators of stone burden remain unclear. METHODS: Patients with renal stones
      treated by flexible URS with holmium laser lithotripsy between October 2009 and
      December 2011 at a single institute were retrospectively evaluated. The SF status
      was determined by kidney-ureter-bladder (KUB) films at postoperative day 1.
      Correlations of possible predictors with the SF status were analyzed using a
      logistic regression model. RESULTS: According to the univariate analysis, the
      following variables were significantly associated with failed treatment: number
      of stones (P = .001), cumulative stone diameter (CSD) (P < .001), stone surface
      area (SA) (P < .001), stone volume (P < .001), and presence of lower pole calculi
      (P = .008). According to the multivariate analysis, the stone volume (P < .001)
      and the CSD (P = .015) were found to be independent predictors of SF status. The
      SA (P = .598) had no significant independent influence on the SF status.
      CONCLUSION: Among the several parameters regarding the renal stone burden, the
      stone volume determined by noncontrast computed tomography and the CSD of the KUB
      were significantly and independently inversely related to the success rate of
      URS. Among the 3 parameters of stone burden, the SA was found to have a lower
      clinical utility and priority as a predictor of a SF status after URS.

PMID- 22658622
TI  - One more chemo or one too many? Defining the limits of treatment and innovation
      in medical oncology.
AB  - During the past few years, debates have frequently erupted in oncology journals
      regarding the question of whether to prolong or end treatment. These debates have
      been informed by developments from both within and outside the field. Within
      Bioethics, some writers have put forward a number of principles for judging the
      legitimacy of medical interventions, notably that of patient autonomy. Broad
      social and political developments have also profoundly affected medical practices
      at the end of life. Though therapeutic options have evolved, whether to stop or
      to pursue treatment in the face of certain death has been a central issue in
      medical oncology since the early 1950s. A critical appraisal of the history of
      this issue can help us to better understand the tangled relationship(s) between
      innovation, "cure," death, and the symptoms and subjective experiences of
      sufferers. This paper addresses an aspect of this complex problem, namely how
      limits are established regarding both treatment and therapeutic innovation near
      the end of life. Utilizing a grounded theory and situational analysis approach it
      traces how the issues at stake were defined and the ways in which the dilemma was
      progressively transformed as a result of the combined effects of a proliferating
      number of stakeholders, molecules, instruments, and techniques. It discusses
      three different moments, as they epitomize how the links between chemotherapy and
      palliation were construed through the evolving forms of clinical research and
      innovative therapies.

PMID- 22658623
TI  - "They should take time": disclosure of clinical trial results as part of a social
      relationship.
AB  - Disclosing overall scientific results to clinical trial participants has become
      an ethical obligation. Here we studied how participants understand these results
      in view of their experience of clinical trials and illness in general and what
      modes of disclosure they preferred. Interviews were conducted with 29 breast
      cancer patients in France during 2009, using an in-depth qualitative approach.
      The findings obtained show that the "results" of research are understood quite
      differently by various patients depending on their expectations about clinical
      trials. Most of the women interviewed expected to receive personally tailored
      results at an individual encounter with their own clinical oncologist. Their
      preferred mode of disclosure was a consultation with their doctors because
      personal encounters promote mutual recognition and set up a symbolic process of
      exchange. The results of this study show that medical interventions should not be
      regarded solely from the technical point of view, but also in terms of the social
      relationships involved.

PMID- 22658624
TI  - On ethical locations: the good death in Thailand, where ethics sit in places.
AB  - In this article, I use ethnographic data on end-of-life care in Northern Thailand
      to address the relationship between ethics and place. My analysis is based on
      fieldwork conducted in 2007-2008, consisting of twenty in-depth oral life
      histories of dying patients; ninety-five interviews with patients, family members
      and caretakers; fifty-four interviews with providers, administrators, civil
      society leaders and other key informants; as well as participant-observation of
      care of patients at the deathbed. In Northern Thailand, many feel that it is
      ethical to withdraw life support in the home, but unethical to withdraw it in the
      hospital. This is because the place of death is partly responsible for the
      quality of rebirth. Hospitals, on one hand, are powerful for saving lives; but as
      places to die, they are amoral, dangerous, devoid of ceremonial history and
      haunted by spirits. Homes, on the other hand, are optimal for dying because they
      are imbued with moral power from a history of beneficial ceremony and family
      living. Hospitalized patients at the edge of death are often rushed home by
      ambulance to withdraw life support in the more ethical place. I argue that the
      two places can be considered different ethical locations, because each is
      inhabited by a unique ethical framework governing withdrawal of life support.
      This concept has implications for the contemporary globalization of bioethics and
      for understanding practices that arise around ethically charged decisions.

PMID- 22658625
TI  - Formulation of work stress in 1960-2000: analysis of scientific works from the
      perspective of historical sociology.
AB  - During the latter part of the 20th century, work stress became an important
      societal issue and a huge amount of scientific attention went to studying it.
      This paper examines the process of formulating and defining the concept of work
      stress in the occupational health sciences and in industrial and organizational
      psychology from the early 1960s to the late 1990s. The empirical material of the
      study encompasses 108 scientific articles, books, book chapters, 'state of the
      art' reviews, book reviews, and written conference presentations. The data are
      analysed in the frameworks of historical sociology, critical psychology, and the
      anthropology of knowledge. We argue that work stress as a life-structuring
      concept gained ground in psychosocial and occupational health sciences (and also
      in lay understanding) in the 1960s simultaneously with the rise of social
      reformist movements that called for fundamental changes emphasizing democratic
      and human-orientated work organizations and socially responsible values. With the
      passing of time, however, the focus on structural improvement of work life waned
      and the emphasis shifted towards the apolitical occupational health aspects of
      work stress. Researchers with a psychological orientation emphasized micro-level
      characteristics as factors affecting work stress, whereas stress-orientated
      epidemiologists turned to the study of specific occupational stress models and/or
      risk factors. The emergence and development of work stress research can be seen
      as a chain of attempts to define and identify new risks and experiences occurring
      in work life. The process, driven by a gradual shift from industrial environments
      towards organizational frameworks characterized by social and psychological
      dimensions, reflected the overall shift towards modern democratic work life and
      the information society in which employees' emotions and well-being became an
      issue.

PMID- 22658626
TI  - Analysis of colistin A and B in fishery products by ultra performance liquid
      chromatography with positive electrospray ionization tandem mass spectrometry.
AB  - A rapid and simple method for the determination of colistin A and B in fishery
      products by reversed phase ultra performance liquid chromatography with positive
      electrospray ionization tandem spectrometry (UPLC-ESI-MS/MS) method was
      described. The samples were extracted with 1.0 mol/L of hydrochloric acid in
      methanol-water and then purified on the PLS solid phase extraction columns. Then
      the eluate was evaporated to less than 1 mL under a gentle stream of nitrogen at
      40  degrees C and formic acid-acetonitrile-water (0.2/10/90, v/v/v) was added to
      adjust volume to 1 mL final volume. An aliquot (10 MUL) was injected onto the LC
      column for analysis with the mobile phase of 0.2% formic acid in acetonitrile and
      0.2% formic acid in water at 0.20 mL min-1. Multiple reaction monitoring was
      performed using precursor-product ion combinations. Calibration curves were
      linear from 200 ng/mL to 2000 ng/mL for colistin A and B. Mean recoveries were
      between 72.9% and 82.9%. The LOD was 10.0 MUg/kg and LOQ was 40.0 MUg/kg. The
      intra-day assay precision values for QC samples were between 2.17% and 9.00%, and
      inter-day values were between 2.80% and 6.97%. The method has merits of
      simplicity, sensitivity and rapidity, and it can be used for the determination of
      colistin A and B in fishery products.

PMID- 22658627
TI  - Evaluation of free-form IOL topographies by clinically available topographers.
AB  - PURPOSE: No commercially available device for measuring individual IOL surface
      topographies exists on the market. The purpose of this paper is to show the
      applicability of clinically available corneal topographers for measuring
      individual IOLs consisting of a spherical surface on one side and a freeform
      surface on the other side. METHODS: Three measurement principles (Placido rings:
      Tomey TMS-2N, Scheimpflug: Oculus Pentacam, optical coherence tomography: Tomey
      CASIA) are applied in determining the IOLs' surface and compared against the
      design data used for producing the surfaces. Spherical and freeform IOLs are
      measured and analysed in both radius of curvature (ROC) and higher-order residual
      parameters by analysing the residuals. RESULTS: Repeatability and reproducibility
      measurements show a sub-MUm precision for the TMS-2N system, while the Pentacam's
      values are located around 10MUm and the CASIA system's values gather around
      20MUm. The TMS-2N system works best at detecting a sample's ROC and residual
      properties within the range of 8mm to 13.5mm mean ROC. In this range, the
      deviations from the theoretical ROC are about 45MUm. The Pentacam doesn't have
      this limitation, but faces problems with exporting measurements of freeform
      surfaces. In some circumstances the program crashes and prevents the export. If
      being able to export the Pentacam measurements show an average deviation of
      100MUm from the theoretical ROC value. The CASIA system shows high amounts of
      noise which makes it not applicable in this field, having deviations of several
      100MUm from the theoretical ROC value. Residual comparison for the higher-order
      samples shows sub-MUm precision for the TMS-2N, about 1MUm precision for the
      Pentacam and several MUm for the CASIA system. The values for the customized
      samples are slightly increased, several MUm for the TMS-2N, up to 30MUm for the
      Pentacam system and around 75MUm for the CASIA system. CONCLUSION: The TMS-2N
      system is an appropriate device for measuring individual IOL surface topographies
      for ROCs between 8mm to 13.5mm. The Pentacam and CASIA induced relatively high
      level of variation and noise. Future application of the TMS-2N in this field will
      reveal its long-term statistics.

PMID- 22658628
TI  - T cell control of malaria pathogenesis.
AB  - Transmission of Plasmodium from mosquito to the mammalian host leads to a
      clinically silent pre-erythrocytic stage of malaria infection, and subsequent
      cyclical erythrocytic invasion associated with disease. Recent evidence
      demonstrates that it is the interplay between CD4+ and CD8+ T cells, and the
      regulation of their response, throughout infection that dictates immunity and the
      pathogenesis of malaria. The elicited T cell response is context dependent,
      influenced by diverse host and parasite factors, necessitating the development of
      a unifying model of T cell potential during Plasmodium infection. Only then can
      we predict their capacity to dictate the outcome of human disease.

PMID- 22658630
TI  - Infectivity of PRRS virus in pig manure at different temperatures.
AB  - PRRSv is an economically important swine pathogen which can be disseminated from
      infected pig herds via movement of contaminated manure. The process of manure
      handling and inadequate cleaning of transport vehicles are commonly implicated as
      sources of PRRSv transmission. Stability of PRRSv in pig manure at different
      temperatures is unknown. The objective of this study was to determine PRRSv
      infectivity half-life in manure and in a cell culture medium at 4, 20, 60 and 80
      degrees C. To assure sample consistency across the study, all samples were
      prepared from common homogenized solutions (MEM and manure) and frozen at -20
      degrees C. Samples were thawed, transferred to a water bath set at a specific
      temperature, inoculated with 100 MUl of PRRSv at designated time points and then
      tested for virus infectivity. Regression models were created to estimate PRRSv
      half-life based on incubation temperature. There was an exponential decrease in
      PRRSv infectivity with increasing temperature. At every temperature tested, PRRSv
      had shorter half-life when incubated in manure compared to MEM. PRRSv half-life
      in MEM and manure was estimated at 112.6 and 120.5 h at 4 degrees C, 14.6 and
      24.5 h at 20 degrees C, 1.6 and 1.7 h at 40 degrees C, 2.9 and 8.5 min at 60
      degrees C, and 0.36-0.59 min at 80 degrees C, respectively. Results of this study
      can be used as basis for developing strategies to inactivate PRRSv present in
      manure-contaminated environments using heating treatments. For example, these
      data suggest that submitting transport trailers to temperature of 50 degrees C
      for 8h would decrease PRRSv from 10(6) TCID(50)/ml to less than 10(1)
      TCID(50)/ml.

PMID- 22658629
TI  - The flagella of F18ab Escherichia coli is a virulence factor that contributes to
      infection in a IPEC-J2 cell model in vitro.
AB  - Bacterial flagella contribute to pathogen virulence; however, the role of
      flagella in the pathogenesis of F18ab E. coli-mediated swine edema disease (ED)
      is not currently known. We therefore evaluated the role of flagella in F18ab E.
      coli adhesion, invasion, biofilm formation, and IL-8 production using an in vitro
      cell infection model approach with gene-deletion mutant and complemented
      bacterial strains. We demonstrated that the flagellin-deficient fliC mutant had a
      marked decrease in the ability to adhere to and invade porcine epithelial IPEC-J2
      cells. Surprisingly, there was no difference in adhesion between the F18 fimbriae
      deficient DeltafedA mutant and its parent strain. In addition, both the DeltafedA
      and double DeltafliCDeltafedA mutants exhibited an increased ability to invade
      IPEC-J2 cells compared to the wild-type strain, although this may be due to
      increased expression of other adhesins following the loss of F18ab fimbriae and
      flagella. Compared to the wild-type strain, the DeltafliC mutant showed
      significantly reduced ability to form biofilm, whereas the DeltafedA mutant
      increased biofilm formation. Although DeltafliC, DeltafedA, and
      DeltafliCDeltafedA mutants had a reduced ability to stimulate IL-8 production
      from infected Caco-2 cells, the DeltafliC mutant impaired this ability to a
      greater extent than the DeltafedA mutant. The results from this study clearly
      demonstrate that flagella are required for efficient F18ab E. coli adhesion,
      invasion, biofilm formation, and IL-8 production in vitro.

PMID- 22658631
TI  - Cell therapy for left ventricular dysfunction: an overview for cardiac
      clinicians.
AB  - Cell therapies specifically targeting heart failure could greatly decrease
      morbidity and burgeoning health care costs worldwide. Due to the great number of
      cell types being investigated, navigating the cardiovascular regeneration field
      can be difficult. This brief review gives an overview of the main cell types
      being explored for cardiac cell therapy. These include populations from extra
      cardiac sources (skeletal myoblasts, bone marrow derived mononuclear cells,
      endothelial progenitor cells, bone marrow or adipose derived mesenchymal stem
      cells and embryonic or induced pluripotent stem cells as well as newly discovered
      cardiac stem cell populations (isl1(+), c-kit(+), sca1(+), sca1(+)/pdgfralpha(+),
      cardiosphere derived, cardiac side-population and epicardium derived cells).
      Although clinical trials using both groups of cell sources have been performed,
      the vast majority of studies have used bone marrow mononuclear cells. The current
      wave of clinical trials includes large studies refining specifics of bone marrow
      mononuclear cell therapy and early phase trials of mesenchymal stem cell and
      cardiac stem cell populations. Embryonic stem cell derived therapies are being
      studied in large animal models with the aim of swift progression to clinical
      trials. Lessons learnt from the intense investigation in this infant field have
      resulted in rapid translational progress and it is likely that several clinical
      products/protocols for cardiac repair will be available in the not too distant
      future.

PMID- 22658632
TI  - Partial descending thoracic aortic replacement for chronic Type B dissection.
AB  - Repair of chronic Type B aortic dissection can be technically challenging. Here
      we describe a technique for the partial replacement of the descending thoracic
      aorta that minimises operative risk and avoids full replacement of the thoraco
      abdominal aorta. This approach can be considered when there is heterogeneous
      perfusion of abdominal viscera by the true and false lumens of the chronically
      dissected aorta.

PMID- 22658633
TI  - Giant congenital fistula of the circumflex coronary artery with drainage into
      right atrium.
AB  - A dilated and tortuous fistula from circumflex coronary artery draining into the
      right atrium was diagnosed by transthoracic echocardiography and selective
      angiography in a 64-year old female. Transcatheter closure was excluded by the
      cardiologist because of the presence of a large huge at the drainage site so the
      patient was scheduled for surgical ligation. Intraoperative and postoperative
      controls were performed by echocardiography. The Authors discuss on differential
      diagnosis, indications and types of treatment in all cases presenting coronary
      artery fistula.

PMID- 22658634
TI  - Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded
      oxidation-sensitive polymersomes.
AB  - While current subunit vaccines successfully induce humoral immune responses, a
      need exists for vaccine strategies to elicit strong cell-mediated immunity to
      address diseases such as cancer and chronic viral infection. Polymersomes are
      stable vesicles composed of self-assembling block copolymers with tunable
      degradation properties allowing delivery of both hydrophilic (within vesicle
      interior) or hydrophobic (within vesicle membrane) payload molecules. Here we
      apply oxidation-sensitive nanoscale polymersomes for both antigen and adjuvant
      delivery to dendritic cell (DC) endosomes. Calcein-loaded polymersomes were
      observed to release their payload initially in multiple DC endosomal compartments
      and subsequently within the cytosol. With either the Toll-like receptor agonists
      gardiquimod or R848 as payloads within the polymersomes, release resulted in DC
      activation, as indicated by induction of inflammatory cytokine expression and
      upregulation of DC maturation surface markers: for example, the ability of
      gardiquimod to induce IL-6 and IL-12 cytokine expression by DCs was enhanced 10
      fold when loaded within polymersomes. With the model antigen ovalbumin as a
      payload, release resulted in CD8(+) T cell cross-priming by promoting protein
      antigen cross-presentation through MHC I, as indicated by activation of OT-I
      CD8(+) T cells. Our results demonstrate that oxidation-sensitive polymersomes can
      function as a vaccine delivery platform for inducing cell-mediated antigen
      specific immune responses.

PMID- 22658635
TI  - PIV quantification of the flow induced by an ultrasonic horn and numerical
      modeling of the flow and related processing times.
AB  - The flow in a confined container induced by an ultrasonic horn is measured by
      Particle Image Velocimetry (PIV). This flow is caused by acoustic streaming and
      highly influenced by the presence of cavitation. The jet-like experimentally
      observed flow is compared with the available theoretical solution for a turbulent
      free round jet. The similarity between both flows enables a simplified numerical
      model to be made, whilst the phenomenon is very difficult to simulate otherwise.
      The numerical model requires only two parameters, i.e. the flow momentum and
      turbulent kinetic energy at the position of the horn tip. The simulated flow is
      used as a basis for the calculation of the time required for the entire liquid
      volume to pass through the active cavitation region.

PMID- 22658636
TI  - Sonochemical synthesis of silver vanadium oxide micro/nanorods: solvent and
      surfactant effects.
AB  - In this investigation, a facile sonochemical route has been developed for the
      preparation of silver vanadium oxide (SVO) micro/nanorods by using silver
      salicylate and ammonium metavanadate as silver and vanadate precursor,
      respectively. Here, silver salicylate, [Ag(HSal)], is introduced as a new silver
      precursor to fabricate AgVO(3) nanorods. The effect of numerous solvents and
      surfactants on the morphology and sonochemical formation mechanism of AgVO(3)
      nanorods was studied. AgVO(3) nanorods were characterized by SEM and TEM images,
      XRD patterns, FT-IR, XPS, and EDS spectroscopy. SEM, TEM, and XRD results showed
      that AgO nanoparticles were formed onto AgVO(3) nanorods in the presence of
      ethanol, cyclohexanol, dimethylsulfoxide (DMSO), and acetone. By using
      polyethylene glycol (PEG-6000) and N,N-dimethylformamide (DMF) as organic
      additives, the thickness of AgVO(3) nanorods decreased.

PMID- 22658637
TI  - TNF-alpha modulates statin effects on secretion and expression of MCP-1, PAI-1
      and adiponectin in 3T3-L1 differentiated adipocytes.
AB  - PURPOSE: Systemic inflammatory conditions, as seen in obesity and in the
      metabolic syndrome, are associated with high plasmatic levels of proatherogenic
      and prothromboticadipokines and low levels of adiponectin. Inhibitors of HMG-CoA
      reductase have beneficial effects in reducing cardiovascular events attributed
      predominantly to its lipid-lowering effects and recent studies suggest that these
      effects might be due to its anti-inflammatory properties. Based on the
      pleiotropic properties of simvastatin we studied the effects of this drug on the
      secretion and expression of adiponectin, PAI-1 and MCP-1 in mature adipocytes
      under baseline conditions and after an inflammatory stimulation. MATERIALS AND
      METHODS: The differentiated adipocytes were incubated with 10 MUM simvastatin or
      vehicle and TNF-alpha 10 ng/mL or vehicle were added to treatment media. After
      24h of incubation, the media was harvested and the proteins of interest were
      analyzed by Multiplex method. Gene expression was analyzed by real time-PCR.
      RESULTS: The addition of TNF-alpha increased the expression and secretion of MCP
      1 and PAI-1. However, stimulation did not interfere with the secretion of
      adiponectin, despite having significantly reduced its expression. Our data also
      demonstrated that simvastatin reduced the expression and secretion of MCP-1,
      under baseline (770.4 +/- 199.9 vs 312.7 +/- 113.7 and 1.00 +/- 0.14 vs 0.63 +/-
      0.13, p<0.05, respectively) and inflammatory conditions (14945 +/- 228.7 vs
      7837.6 +/- 847.4 and 24.16 +/- 5.49 vs 14.97 +/- 2.67, p<0.05, p<0.05,
      respectively). Simvastatin also attenuated the increase in expression and
      secretion of PAI-1 induced by TNF-alpha (16898.6 +/- 1663.3 vs 12922.1 +/- 843.9
      and 5.19 +/- 3.12 vs 0.59 +/- 0.16, respectively p<0.05), but under baseline
      conditions had no effect on the expression or secretion of PAI-1. The statin
      increased the expression of adiponectin under baseline conditions and
      inflammatory stimulation (1.03 +/- 0.08 vs 4.0 +/- 0.96 and 0.77 +/- 0.19 vs 2.16
      +/- 0.23, respectively, p<0.05) and also increased the secretion of this
      adipokine but only with the inflammatory stimulus (5347.7 +/- 1789.3 vs 7327.3 +/
      753.6, p<0.05). CONCLUSIONS: Our findings suggested that simvastatin
      counteracted the stimulatory effect of TNF-alpha on secretion and expression of
      MCP-1, PAI-1 and adiponectin, implying a potential anti-atherogenic effect during
      the inflammatory process; these pleitropic effects were more pronounced with HMG
      CoA reductase inhibitor.

PMID- 22658638
TI  - Enhancing interest in nephrology careers during medical residency.
AB  - Promoting interest in nephrology as a career is vital to sustain a workforce
      adequate to meet the projected demand for nephrologists. The educational
      experiences that internal medicine residents have may play an important role in
      influencing such choices, and attempts to enrich such experiences could prove a
      useful strategy to help facilitate interest in careers in nephrology. Like many
      electives, nephrology rotations typically consist of activities heavily weighted
      toward inpatient care. This type of elective is unlikely to provide a
      representative exposure to the breadth of nephrologists' roles and may lack
      sufficient mentoring opportunities. We describe an innovative design for a
      nephrology elective that provides residents with educational experiences in both
      inpatient and outpatient venues and exposure to faculty with diverse interests
      and areas of expertise. Our experience with this elective in comparison to a
      traditional inpatient-based elective suggests that the combined elective format
      is perceived favorably by medical residents and provides them with a better
      educational experience, more representative exposure to nephrology, positive
      mentoring experiences, and the potential for greater interest in pursuing
      nephrology as a career. Our findings offer the possibility that interventions at
      the level of medical resident education might be a means to help promote interest
      in careers in nephrology.

PMID- 22658640
TI  - Is obstructive sleep apnoea causally related to arterial stiffness? A critical
      review of the experimental evidence.
AB  - Large elastic arteries and smaller muscular conduit arteries become stiffer with
      ageing, a process that is accelerated in the presence of cardiovascular disease
      (CVD). In recent years, numerous techniques have been developed to measure
      arterial stiffness, either in single vessels or in entire muscular arterial
      trees. These techniques have increasingly been shown to improve stratification of
      cardiovascular risk and risk reduction beyond that provided by conventional risk
      factors. Obstructive sleep apnoea (OSA) has been increasingly linked with excess
      cardiovascular morbidity and mortality however the mechanisms are still not well
      understood. Robustly designed studies have shown that treatment of OSA with nasal
      continuous positive airway pressure improves important intermediate risk factors
      for CVD including hypertension and endothelial function. More recently, there has
      been increased exploration of arterial stiffness in both cross-sectional and
      interventional studies in OSA patients. This review aims to give the reader a
      better understanding of the measurement and pathophysiology of arterial stiffness
      as well as providing an indication of how well a prognostic indicator are the
      various measures of arterial stiffness for hard cardiovascular endpoints. A
      critical appraisal is then provided of cross-sectional and interventional studies
      that have explored these same techniques in OSA populations.

PMID- 22658641
TI  - What kind of polyunsaturated fatty acid should we eat to stay healthy?

PMID- 22658639
TI  - The Hippo signaling pathway and stem cell biology.
AB  - Stem cell (SC) activity fluctuates throughout an organism's lifetime to maintain
      homeostatic conditions in all tissues. As animals develop and age, their organs
      must remodel and regenerate themselves in response to environmental and
      physiological demands. Recently, the highly conserved Hippo signaling pathway,
      discovered in Drosophila melanogaster, has been implicated as a key regulator of
      organ size control across species. Deregulation is associated with substantial
      overgrowth phenotypes and eventual onset of cancer in various tissues.
      Importantly, emerging evidence suggests that the Hippo pathway can modulate its
      effects on tissue size by the direct regulation of SC proliferation and
      maintenance. These findings provide an attractive model for how this pathway
      might communicate physiological needs for growth to tissue-specific SC pools. In
      this review, we summarize the current and emerging data linking Hippo signaling
      to SC function.

PMID- 22658642
TI  - Evaluation of nursing adherence to a paper-based graduated continuous intravenous
      regular human insulin infusion algorithm.
AB  - OBJECTIVE: The use of continuous intravenous regular human insulin (RHI) infusion
      is often necessary to achieve glycemic control in critically ill patients.
      Because insulin is a high-risk medication owing to the potential for severe
      hypoglycemia, it is imperative that insulin infusion algorithms are designed to
      be safe, effective, and instructionally clear. The safety and efficacy of our
      intravenous RHI infusion algorithm protocol has been previously established
      (Nutrition 2008;24:536-45); however, the protocol violations by nursing personnel
      were not examined. The objective of this study was to assess nursing adherence to
      our RHI infusion algorithm. METHODS: Continuous RHI infusion algorithm violations
      were retrospectively evaluated in adult patients admitted to a trauma intensive
      care unit who received concurrent continuous enteral and/or parenteral nutrition
      therapy and our algorithm for at least 3 d. Blood glucose (BG) monitoring was
      done every 1 to 2 h with the target BG at 70 to 149 mg/dL (3.9 to 8.3 mmol/L).
      Nursing adherence to the RHI infusion protocol was evaluated for each patient by
      comparing the adjustments in insulin infusion rates documented by the nursing
      personnel with the prescribed adjustments per our graduated continuous
      intravenous RHI infusion algorithm. RESULTS: A total of 4150 BG measurements
      necessitating the determination of the appropriate RHI dosage rate by nursing
      personnel in 40 patients occurred during the observational period. The target BG
      was achieved for a mean of 20 h/d and none of the patients had an episode of
      severe hypoglycemia (BG <40 mg/dL or 2.2 mmol/L). The overall rate of algorithm
      violations was 12.1%. The algorithm violations accounted for a single episode of
      mild to moderate hypoglycemia (BG 40 to 60 mg/dL or 2.2 to 3.3 mmol/L) in 4
      patients and 65 total episodes of hyperglycemia (BG >=150 mg/dL or 8.3 mmol/L) in
      18 patients. CONCLUSION: An adherence rate of nearly 90% is indicative of
      excellent nursing adherence compared with other published paper-based algorithms
      that examined protocol adherence. These data, combined with our previously
      published glycemic control data, indicate that this RHI infusion algorithm is an
      effective one for hyperglycemic trauma patients receiving continuous enteral
      and/or parenteral nutritional therapy.

PMID- 22658643
TI  - Association study of genetic variations in microRNAs with the risk of hepatitis B
      related liver diseases.
AB  - BACKGROUND AND AIMS: MicroRNAs have been recently identified as important
      regulators that influence human carcinogenesis, cancer progression, and the
      interaction between the host and virus. This study investigates an association
      between microRNAs (miR-101-1, miR-101-2, and miR-338) and the risk of liver
      diseases through clearance of hepatitis B virus infection, development of liver
      cirrhosis, and hepatocellular carcinoma occurrence. METHODS: Genetic variations
      were genotyped using the TaqMan assay in 1439 Korean hepatitis B virus patients.
      To investigate the relationship between four polymorphisms in three microRNAs and
      the disease phenotypes, differences in frequency distribution of variations were
      analysed using logistic and multiple regression analyses after adjusting for age
      and gender as covariates. RESULTS: We find that the rs7536540 polymorphism in miR
      101-1 is significantly associated with development of liver cirrhosis and
      hepatocellular carcinoma occurrence. In addition, rs12375841 and its unique
      haplotype (ht2) in miR-101-2 show significant association with clearance of
      hepatitis B virus infection. CONCLUSIONS: To our knowledge, this is the first
      study to examine a relationship between the three microRNA genes and the risk of
      hepatitis B-related liver diseases. We expect that the findings in this study
      will be helpful to further genetic studies in the pathophysiology of hepatitis B
      virus-related liver diseases.

PMID- 22658644
TI  - Chemotherapy in the treatment of anal canal carcinoma.
AB  - Squamous cell carcinomas of the anal canal are generally diagnosed at a localized
      or locally advanced stage and only 5% are metastatic at the time of diagnosis.
      Advanced forms are therefore much rarer than localized forms and usually
      correspond to metachronous metastases of initially localized disease. Systemic
      chemotherapy is indicated for the treatment of both localized disease, in
      combination with radiotherapy, and metastatic disease. The purpose of this
      article is to define the current indications and modalities of chemotherapy in
      the treatment of these cancers based on a review of the published data and in the
      light of available guidelines.

PMID- 22658645
TI  - A plant-tastic treatment for cognitive disorders.

PMID- 22658646
TI  - Source memory errors associated with reports of posttraumatic flashbacks: a proof
      of concept study.
AB  - Flashbacks are involuntary, emotion-laden images experienced by individuals with
      posttraumatic stress disorder (PTSD). The qualities of flashbacks could under
      certain circumstances lead to source memory errors. Participants with PTSD wrote
      a trauma narrative and reported the experience of flashbacks. They were later
      presented with stimuli from flashback and non-flashback parts of their narrative,
      mixed with foils from the narrative of another participant, and judged whether
      they belonged to their own narrative. They also reported whether stimuli elicited
      a flashback during this recognition test. Overall reporting a flashback at test
      was associated with significantly better recognition performance. Flashbacks were
      occasionally reported to foil stimuli, which were then likely to be wrongly
      attributed to the person's own narrative. This provides proof of concept of a
      cognitive mechanism that could potentially account for some cases of false trauma
      memories.

PMID- 22658647
TI  - Phytosterols inhibit the tumor growth and lipoprotein oxidizability induced by a
      high-fat diet in mice with inherited breast cancer.
AB  - Dietary phytosterol supplements are readily available to consumers since they
      effectively reduce plasma low-density lipoprotein cholesterol. Several studies on
      cell cultures and xenograft mouse models suggest that dietary phytosterols may
      also exert protective effects against common cancers. We examined the effects of
      a dietary phytosterol supplement on tumor onset and progression using the well
      characterized mouse mammary tumor virus polyoma virus middle T antigen transgenic
      mouse model of inherited breast cancer. Both the development of mammary
      hyperplastic lesions (at age 4 weeks) and total tumor burden (at age 13 weeks)
      were reduced after dietary phytosterol supplementation in female mice fed a high
      fat, high-cholesterol diet. A blind, detailed histopathologic examination of the
      mammary glands (at age 8 weeks) also revealed the presence of less-advanced
      lesions in phytosterol-fed mice. This protective effect was not observed when the
      mice were fed a low-fat, low-cholesterol diet. Phytosterol supplementation was
      effective in preventing lipoprotein oxidation in mice fed the high-fat diet, a
      property that may explain - at least in part - their anticancer effects since
      lipoprotein oxidation/inflammation has been shown to be critical for tumor
      growth. In summary, our study provides preclinical proof of the concept that
      dietary phytosterols could prevent the tumor growth associated with fat-rich diet
      consumption.

PMID- 22658648
TI  - Chronic treatment with myo-inositol reduces white adipose tissue accretion and
      improves insulin sensitivity in female mice.
AB  - Type 2 diabetes is a complex disease characterized by a state of insulin
      resistance in peripheral tissues such as skeletal muscle, adipose tissue or
      liver. Some inositol isomers have been reported to possess insulin-mimetic
      activity and to be efficient in lowering blood glucose level. The aim of the
      present study was to assess in mice the metabolic effects of a chronic treatment
      with myo-inositol, the most common stereoisomer of inositol. Mice given myo
      inositol treatment (0.9 or 1.2 mg g(-1) day(-1), 15 days, orally or
      intraperitoneally) exhibited an improved glucose tolerance due to a greater
      insulin sensitivity. Mice treated with myo-inositol exhibited a decreased white
      adipose tissue accretion (-33%, P<.005) compared with controls. The decrease in
      white adipose tissue deposition was due to a decrease in adipose cell volume (
      33%, P<.05), while no change was noticed in total adipocyte number. In skeletal
      muscle, in vivo as well as ex vivo myo-inositol treatment increased protein
      kinase B/Akt phosphorylation under baseline and insulin-stimulated conditions,
      suggesting a synergistic action of myo-inositol treatment and insulin on proteins
      of the insulin signalling pathway. Myo-inositol could therefore constitute a
      viable nutritional strategy for the prevention and/or treatment of insulin
      resistance and type 2 diabetes.

PMID- 22658649
TI  - Maternal high-fat intake during pregnancy programs metabolic-syndrome-related
      phenotypes through liver mitochondrial DNA copy number and transcriptional
      activity of liver PPARGC1A.
AB  - In this study, we contrasted the hypothesis that maternal diet during pregnancy
      has an impact on fetal metabolic programming through changes in liver
      mitochondrial DNA (mtDNA) content and transcriptional activity of Ppargc1a and
      that these effects are sex specific. METHODS: Rats were fed either high-fat (HFD)
      or standard chow diet (SCD) during gestation and lactation. The resulting adult
      male and female offspring were fed either HFD or SCD for an 18-week period,
      generating eight experimental groups. RESULTS: Maternal HFD feeding during
      pregnancy is associated with a decreased liver mtDNA copy number (P<.008). This
      effect was independent of the offspring sex or diet, and was significantly
      associated with fatty liver when dams were fed HFD (P<.05, adjusted by
      homeostasis model assessment of insulin resistance, HOMA-IR). We also found that
      maternal HFD feeding results in a male-specific significant reduction of the
      liver abundance of Ppargc1a mRNA (P<.004), which significantly impacted
      peripheral insulin resistance. Liver expression of Ppargc1a was inversely
      correlated with HOMA-IR (R=-0.53, P<.0003). Only male offspring exposed to a
      chronic metabolic insult in adult life were insulin resistant and
      hyperleptinemic, and showed abnormal liver and abdominal fat accumulation. Liver
      abundance of Tfam, Nrf1, Hnf4a, Pepck and Ppparg mRNA was not associated with
      maternal programming. In conclusion, maternal high-fat diet feeding during
      pregnancy programs liver mtDNA content and the transcriptional activity of
      Ppargc1a, which strongly modulates, in a sex-specific manner, glucose homeostasis
      and organ fat accumulation in adult life after exposure to a nutritional insult.

PMID- 22658650
TI  - Chromatin regulation of flowering.
AB  - The transition to flowering is a major developmental switch in the life cycle of
      plants. In Arabidopsis (Arabidopsis thaliana), chromatin mechanisms play critical
      roles in flowering-time regulation through the expression control of key
      flowering-regulatory genes. Various conserved chromatin modifiers, plant-specific
      factors, and long noncoding RNAs are involved in chromatin regulation of
      FLOWERING LOCUS C (FLC, a potent floral repressor). The well-studied FLC
      regulation has provided a paradigm for chromatin-based control of other
      developmental genes. In addition, chromatin modification plays an important role
      in the regulation of FLOWERING LOCUS T (FT, encoding florigen), which is widely
      conserved in angiosperm species. The chromatin mechanisms underlying FT
      regulation in Arabidopsis are likely involved in the regulation of FT relatives
      and, therefore, flowering-time control in other plants.

PMID- 22658651
TI  - Regulating the reapers: activating metacaspases for programmed cell death.
AB  - Research during the past two decades has revealed that specialized cysteine
      proteases act as conserved initiators or executioners for programmed cell death
      (PCD) in eukaryotes. Caspases were first identified as common regulators of PCD
      in metazoans, whereas the role of metacaspases (MCs) as regulators of cellular
      suicide in plants has only been shown genetically in the past several years.
      Together with recent biochemical and molecular characterizations of some of the
      representative MCs from different model systems, multiple mechanisms that can
      mediate the post-translational regulation of these proteases are beginning to
      emerge. Further elucidation of these regulatory pathways and definition of the
      downstream degradomes targeted by MCs should lead to a better understanding of
      cell death control in plants, protozoans, and fungi.

PMID- 22658652
TI  - Rad knockdown induces mitochondrial apoptosis in bortezomib resistant leukemia
      and lymphoma cells.
AB  - To understand the molecular mechanism(s) underlying bortezomib resistance, we
      sought to identify potential target genes that were differentially expressed in
      bortezomib-resistant leukemia cells versus parental controls. Microarray analysis
      revealed that the mRNA levels of Rad (Ras associated with diabetes) were higher
      in the bortezomib-resistant Jurkat (Jurkat-R) cells than in the parental control
      cells. The importance of Rad for bortezomib resistance was supported by three
      observations. First, Rad knockdown overcame bortezomib resistance and induced
      mitochondrial apoptosis via Noxa/Bcl-2 modulation. Second, Rad decreased cell
      death in response to bortezomib. Third, leukemia and lymphoma cell lines (K-562,
      Raji, IM-9 and Jurkat-R) with elevated Rad expression levels showed higher
      degrees of bortezomib resistance versus those (Sup-B15, JVM-2, U266 and Jurkat)
      with low Rad expression levels (r=0.48, P=0.0004). Thus, Rad over expression
      could be a molecular target to improve bortezomib sensitivity in human leukemia
      and lymphoma.

PMID- 22658653
TI  - Thermal and mechanical pain thresholds in patients with fluctuating Parkinson's
      disease.
AB  - Study results evaluating pain thresholds in patients with Parkinson's disease
      (PD) vary widely. Thus, we designed our study to determine the effects of
      levodopa on the thresholds of pressure (PPT), heat (HPT) and cold pain (CPT) in
      PD patients with motor fluctuations (18 patients: 10 men, 8 women; age: 65 +/- 10
      years; mean disease duration: 11.6 +/- 6 years), six of whom (33%) reported pain
      related to their disease. We compared these thresholds in patients in the ON and
      OFF states with those in 18 age- and sex-matched controls. Pain thresholds were
      assessed over: the frontal bones, C5-C6 zygapophyseal joints and second
      metacarpals (PPT); the dorsal aspect of the hand (HPT and CPT); and the tibialis
      anterior (TA) muscles. PD patients in the OFF state had lower PPT thresholds at
      all sites (P < 0.001) than healthy controls. Moreover, HPT and CPT thresholds
      were lower at all sites except over the TA muscle (P < 0.01). In the ON state,
      the PPT and CPT thresholds in PD patients were lower than in controls at all
      points, except over the TA (CPT) and the second metacarpals (PPT) P < 0.01. Pain
      thresholds were no different in PD patients in the ON or OFF state (P > 0.10),
      and the existence of pain did not influence the results. We detected mechanical
      and thermal pain hypersensitivity in PD patients in the OFF state, and levodopa
      administration did not increase these thresholds. Thus, while dopamine may
      modulate pain responses, other mechanisms are likely to be implicated in the
      modulation of these pain responses in PD patients.

PMID- 22658656
TI  - Liquid chromatography-nuclear magnetic resonance coupling as alternative to
      liquid chromatography-mass spectrometry hyphenations: curious option or powerful
      and complementary routine tool?
AB  - Combining the most powerful separation techniques, i.e. liquid chromatography
      (LC) or capillary electrophoresis (CE) with a information rich detection system -
      the mass spectrometer or the nuclear magnetic resonance (NMR) spectrometer - has
      been pursued for more than three decades. This compilation shall provide an
      overview of the advantages and limitations of the LC-NMR hyphenation in the light
      of its most valued application-the unequivocal analyte identification. Especially
      the post LC trapping of analytes with an in-line solid phase extraction (SPE)
      device prior to transferring the analyte of interest to the NMR spectrometer (LC
      SPE-NMR) proved to be a robust installation allowing a significant cut-down of
      the amount of analyte needed for the generation of high quality heteronuclear NMR
      shift correlation data. Different available technical realizations will be
      discussed and typical application examples from natural product research and from
      industrial settings will be given.

PMID- 22658654
TI  - Genomic determinants of motor and cognitive outcomes in Parkinson's disease.
AB  - BACKGROUND: Little is known regarding genetic factors associated with motor or
      cognitive outcomes in Parkinson's disease (PD). OBJECTIVE: To identify common
      genetic variants associated with motor and cognitive outcomes in PD. METHODS: The
      sample consisted of 443 PD cases included in the first genome-wide association
      study (GWAS) of PD. Methods included telephone interview assessments of motor and
      cognitive outcomes, a median 9 years following the initial clinical assessments.
      Analyses included Cox proportional hazard models to study the association of
      198,345 single nucleotide polymorphisms (SNPs) with survival free of Hoehn and
      Yahr stage >= 4 (motor outcome), and either TICS-M <= 27 or AD-8 >= 2 (cognitive
      outcomes). RESULTS: The SNP rs10958605 in the C8orf4 gene had the smallest p
      value in analyses of the motor outcome (HR = 1.81; 95% CI = 1.42-2.31; p = 1.51 *
      10(-6)). The SNP rs6482992 in the CLRN3 gene had the smallest p value in analyses
      of the cognitive outcome (HR = 2.03, 95% CI 1.47-2.79, p = 4.08 * 10(-6)).
      However, no SNP associations were significant after Bonferroni correction. The
      C8orf4 gene had small p values for both motor and cognitive outcomes,
      highlighting inflammation as a possible pathogenesis mechanism for progression in
      PD. CONCLUSIONS: This study suggests that common variants in several genes may be
      associated with motor and cognitive outcomes in PD, with biological plausibility.

PMID- 22658655
TI  - Global cancer transitions according to the Human Development Index (2008-2030): a
      population-based study.
AB  - BACKGROUND: Cancer is set to become a major cause of morbidity and mortality in
      the coming decades in every region of the world. We aimed to assess the changing
      patterns of cancer according to varying levels of human development. METHODS: We
      used four levels (low, medium, high, and very high) of the Human Development
      Index (HDI), a composite indicator of life expectancy, education, and gross
      domestic product per head, to highlight cancer-specific patterns in 2008 (on the
      basis of GLOBOCAN estimates) and trends 1988-2002 (on the basis of the series in
      Cancer Incidence in Five Continents), and to produce future burden scenario for
      2030 according to projected demographic changes alone and trends-based changes
      for selected cancer sites. FINDINGS: In the highest HDI regions in 2008, cancers
      of the female breast, lung, colorectum, and prostate accounted for half the
      overall cancer burden, whereas in medium HDI regions, cancers of the oesophagus,
      stomach, and liver were also common, and together these seven cancers comprised
      62% of the total cancer burden in medium to very high HDI areas. In low HDI
      regions, cervical cancer was more common than both breast cancer and liver
      cancer. Nine different cancers were the most commonly diagnosed in men across 184
      countries, with cancers of the prostate, lung, and liver being the most common.
      Breast and cervical cancers were the most common in women. In medium HDI and high
      HDI settings, decreases in cervical and stomach cancer incidence seem to be
      offset by increases in the incidence of cancers of the female breast, prostate,
      and colorectum. If the cancer-specific and sex-specific trends estimated in this
      study continue, we predict an increase in the incidence of all-cancer cases from
      12.7 million new cases in 2008 to 22.2 million by 2030. INTERPRETATION: Our
      findings suggest that rapid societal and economic transition in many countries
      means that any reductions in infection-related cancers are offset by an
      increasing number of new cases that are more associated with reproductive,
      dietary, and hormonal factors. Targeted interventions can lead to a decrease in
      the projected increases in cancer burden through effective primary prevention
      strategies, alongside the implementation of vaccination, early detection, and
      effective treatment programmes. FUNDING: None.

PMID- 22658657
TI  - Alkaline-stable peptide ligand affinity adsorbents for the purification of
      biomolecules.
AB  - A strategy of modification of resin surface chemistry is presented to produce
      hydrophilic peptide-based alkaline-stable affinity adsorbents for the
      purification of biopharmaceuticals from complex media. In this work, the peptide
      based affinity adsorbent HWRGWV-Toyopearl resin for the purification of IgG is
      presented as an example. When prepared by direct peptide synthesis on the
      chromatographic matrix, the peptide-based resin showed lability under alkaline
      conditions. In fact, the regeneration with aqueous 0.1 M NaOH caused the leaching
      of 40% of the peptide ligand, resulting in a decrease of IgG yield from 85% to
      23%. It was found that the ligand leaching was caused by the coupling of a
      significant amount of peptide by alkaline-labile ester bonds. A method was
      designed to prevent the formation of ester bonds and allow the synthesis of the
      ligand exclusively on alkaline-stable bonds. The method consists in activating
      the hydrophilic base resin, blocking the hydroxyl groups responsible for alkaline
      lability and performing the peptide synthesis exclusively via alkaline-stable
      amide bonds. Repeated cycles of IgG purification from a cell culture medium were
      performed, each followed by cleaning with aqueous NaOH (0.1 M, 0.5 M and 1 M).
      The IgG yield decreased from 91% to 85% after 200 purification cycles with 0.1 M
      NaOH. However, the IgG purity remained almost constant at around 95% based on SDS
      PAGE analysis. The procedure presented is rapid, efficient and inexpensive and
      does not require any equipment other than the conventional instrumentation for
      peptide synthesis. The method also has a broad application since it is valid for
      any peptide ligand identified for the purification of a biopharmaceutical target.

PMID- 22658658
TI  - Determination of Delta9-tetrahydrocannabinol and 11-nor-9-carboxy-Delta9
      tetrahydrocannabinol in water samples by solid-phase microextraction with on
      fiber derivatization and gas chromatography-mass spectrometry.
AB  - A new method for the determination of two cannabinoids, Delta9
      tetrahydrocannabinol (THC) and 11-nor-9-carboxy-Delta9-tetrahydrocannabinol
      (THCCOOH), in wastewater samples is proposed using solid-phase microextraction
      (SPME) as extraction technique and gas chromatography coupled to mass
      spectrometry (GC-MS) as determination technique. Several parameters involved in
      SPME extraction were studied and optimized (time, temperature, volume, pH and
      ionic strength of sample, and type of fiber). Moreover two derivatization
      reagents, N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) and N-methyl-N
      (tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), were studied in depth,
      providing MSTFA the best results. The use of internal standard calibration (with
      their corresponding deuterated analogs) allows avoiding standard addition
      calibration for the quantification of samples. Under optimal conditions, limits
      of detection at low nanograms per liter were achieved (1.0 and 2.5 ng L-1 for THC
      and THCCOOH respectively). Precision (RSD<15%) and trueness (92-112% relative
      recovery) were also satisfactory. Analysis of several samples from a wastewater
      treatment plant (WWTP) shows the presence of cannabinoids at notable
      concentrations in raw wastewater (12-35 ng L-1 for THC and 50-153 ng L-1 for
      THCCOOH) and an incomplete removal, which translates into their detection in the
      receiving river.

PMID- 22658659
TI  - Extraction and purification of recombinant human serum albumin from Pichia
      pastoris broths using aqueous two-phase system combined with hydrophobic
      interaction chromatography.
AB  - Recombinant human serum albumin (rHSA) is considered as an alternative of human
      serum albumin and used to treat patients with severe burn, shock or blood loss.
      However, separation and purification of rHSA are difficult and have become the
      bottle neck in industrial production. In this study, ethanol/K2HPO4 aqueous two
      phase system (ATPS) and hydrophobic interaction chromatography (HIC) were
      integrated to provide a new approach for the extraction and purification of rHSA
      from high density fermentation broth. Using a 0.01-73 L ATPS scale, the
      extraction of rHSA from the fermentation broth attained an average recovery of
      100.4%. At the same time, 99.8% of cells and 87.2% of polysaccharides as well as
      some other protein impurities were also removed. The activity of proteinase A in
      the broth was also remarkably decreased. The purified rHSA appeared as a single
      band on reduced SDS-PAGE gel, and it had a purity of 99.1% as determined by HPLC.
      It was essentially identical to the plasma-derived HSA in terms of molecular
      weight and circular dichroism spectrum. The total recovery of rHSA was 75.2%,
      which was 1.1-2.0 times higher than that obtained from conventional processes.
      Residual polysaccharide was reduced to 1.61 MUg/mg rHSA and the degree of
      coloring was lower than that of plasma-derived HSA. The procedure employed in
      this study has the advantages of simple operation, shorter time, low energy
      consumption and high yield, and it could produce rHSA with high purity. It is
      therefore suitable in the production of rHSA and other biological products
      produced by high-density fermentation.

PMID- 22658660
TI  - Cation separation and preconcentration using columns containing cyclen and cyclen
      resorcinarene derivatives.
AB  - The selectivity and separation of transition metal ions on two columns packed
      with cyclen-based macrocycles adsorbed onto 55% cross-linked styrene
      divinylbenzene resin are presented. The N-cyclen and cyclen-resorcinarene
      stationary phases were made by adsorbing hydrophobically substituted N-cyclen or
      a cyclen-resorcinarene derivative (cyclenbowl) on the resin, respectively. The
      stability constants of cyclen with transition metal ions demonstrate that cyclen
      has selectivity for Cu2+ over other transition metal ions. Mn2+, Co2+, Ni2+,
      Cd2+, and Zn2+ ions were separated from Cu2+ using HNO3 eluent with the
      cyclenbowl column. The preconcentration of Cu2+ in parts per billion level from a
      high concentration matrix of Mn2+, Co2+, Ni2+, Cd2+, and Zn2+ ions was achieved
      in the cyclenbowl column using a nitric acid eluent gradient. Recovery of Cu2+ at
      >98% was obtained based on direct interaction of metal ion and cyclen. Although
      Mn2+, Co2+, Ni2+, Cd2+, and Zn2+ were not separated by HNO3 eluent, addition of
      oxalic acid yielded a very good separation. A retention mechanism is proposed for
      the latter system in which the protonated cyclen units attract negatively charged
      HC2O4- ions that cooperate with cyclen sites in retaining transition metal ions.

PMID- 22658661
TI  - Dispersive micro solid-phase extraction of triazines from waters using oxidized
      single-walled carbon nanohorns as sorbent.
AB  - This article evaluates the usefulness of dispersed single-walled carbon nanohorns
      as sorbent for the isolation and preconcentration of triazines from waters. For
      this purpose, the carbon nanoparticles were oxidized to increase their solubility
      in aqueous media in order to obtain a stable dispersion that can be used as
      extractant of the selected pollutants. Then, 1 mL of the dispersion containing
      the oxidized single-walled carbon nanohorns at a concentration of 0.2 g/L was
      added to 10 mL of sample and stirred for 2 min using a vortex. Then, the whole
      volume was passed through a disposable 0.45 MUm Nylon filter which retained the
      nanoparticles enriched with the triazines. Further elution with methanol
      permitted the gas chromatographic analysis of the analytes and subsequent
      identification and quantification by mass spectrometry working under the selected
      ion monitoring mode (SIM). The limits of detection (LODs) were in low nanogram
      per liter level, which allowed the detection of the selected triazines at the
      concentration stated by legislation. The precision of the method, calculated as
      relative standard deviation, was acceptable in all instances. Finally, the
      recovery study carried out in different water samples provided average values
      between 87% and 94%. The results obtained revealed the applicability of oxidized
      single-walled carbon nanohorns for the proposed analytical problem.

PMID- 22658662
TI  - Can we predict the severity of pulmonary hypertension in patients with
      scleroderma?
AB  - OBJECTIVES: To describe the clinical-biological characteristics of patients with
      scleroderma (SSc) and pulmonary artery hypertension (PAH). To establish the
      relationship between pulmonary functional tests (PFT), Doppler echocardiography
      (ECHO) and the severity of the PAH. MATERIAL AND METHODS: Retrospective study of
      patients with scleroderma treated at a tertiary center. All participants received
      a protocol study, which included a complete analysis and additional tests:
      Doppler Echocardiography and pulmonary functional tests (PFT) with carbon
      monoxide diffusing capacity (DLCO). RESULTS: Overall, 331 patients were treated,
      including 68 (20.5%) with PAH. The limited subtype of Scleroderma was the most
      prevalent. The Person's correlation coefficient was used for the following
      variables: FVC-sPAP, FVC/DLCO-sPAP, DLCO-sPAP and TRV-sPAP, showed a significant
      moderate linear association in the relationship DLCO-sPAP and TRV-sPAP. 29 deaths
      occurred, with 12 of them related to PAH. The median time between the PAH
      diagnosis and death was 1.8 years. CONCLUSIONS: The decrease in DLCO and the
      increase in TRV are negative predictor factor of PAH which, at the same time,
      means a worsening prognosis for patients with Scleroderma.

PMID- 22658663
TI  - Phenotypic characteristics and virulence genotypes of Trueperella
      (Arcanobacterium) pyogenes strains isolated from European bison (Bison bonasus).
AB  - Trueperella (Arcanobacterium) pyogenes is an opportunistic animal pathogen, which
      in European bison is associated with different suppurative infections mainly of
      the urogenital tract. Little is known about the virulence of this bacterium and
      about the pathogenesis of infections. The main objective of this study was to
      determine phenotypic properties and virulence genotypes of the twenty-five T.
      pyogenes strains isolated from lesions in various tissues of free-living European
      bison. Classical bacteriological methods were used for phenotypic
      characterization. Genes encoding seven known and putative virulence factors of T.
      pyogenes were detected by PCR technique. Analysis of 16S rDNA partial sequences
      was performed to establish phylogenetic relationships of the isolated strains.
      All isolates showed typical morphological features of T. pyogenes and variable
      biochemical activity. Most of them displayed a strong positive effect in
      synergistic CAMP test. For all isolates the 16S rRNA gene partial sequence was
      identical to that of the T. pyogenes reference strain. All isolates carried the
      plo and fimA genes, while the nanH, nanP, cbpA, fimC and fimG genes were present
      in 40, 44, 12, 88 and 24% of the isolates, respectively. The T. pyogenes strains
      isolated from European bison represented various phenotypes and virulence
      genotypes, but there was no association between the investigated properties of
      the bacteria and the type of anatomopathological lesions from which they were
      isolated. These results indicate that the studied virulence factors of T.
      pyogenes are not significant determinants of the localization and type of
      infection caused by this bacterium.

PMID- 22658664
TI  - Phagolysosome maturation of macrophages was reduced by PE_PGRS 62 protein
      expressing in Mycobacterium smegmatis and induced in IFN-gamma priming.
AB  - Mycobacterium bovis parasitizes host macrophages and has developed strategies to
      survive within macrophages. Research on mycobacteria-specific PE_PGRS genes
      indicates that they code for cell surface proteins that may influence virulence.
      To further elucidate the molecular pathogenesis of tuberculosis and host response
      to M. bovis, we explored the mechanisms by which PE_PGRS62 protein increase
      persistence of mycobacterium within host macrophages. We found that the M.
      smegmatis strain expressing M. bovis PE_PGRS 62 protein reduced phagolysosome
      maturation in human macrophages, and significantly decreased the mRNA expression
      of IL-1beta in a dose- and time-dependent. We identified that IFN-gamma priming
      of macrophages immediately prior to infection with PE_PGRS62 expressing M.
      smegmantis, enhanced the maturation of phagolysosomes and induced IL-1beta
      production both that the protein and mRNA levels and further activated the NF
      kappaB pathway. Overall, we demonstrated that PE_PGRS62 protein altered the
      immune environment of the host cells, which suggested that the pathogenic
      PE_PGRS62 protein altering the immune mechanism might be involved in the
      pathogenesis of mycobacterial disease and hence influenced host cell responses to
      M. bovis infection.

PMID- 22658665
TI  - Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in
      pancreatitis.
AB  - BACKGROUND: The pancreas is one of the primary organs affected by dysfunction of
      the cystic fibrosis transmembrane conductance regulator (CFTR) protein. While
      exocrine pancreatic insufficiency is a well-recognized complication of cystic
      fibrosis (CF), symptomatic pancreatitis is often under-recognized. RESULTS: The
      aim of this review is to provide a general overview of CFTR mutation-associated
      pancreatitis, which affects patients with pancreatic sufficient CF, CFTR-related
      pancreatitis, and idiopathic pancreatitis. The current hypothesis regarding the
      role of CFTR dysfunction in the pathogenesis of pancreatitis, and concepts on
      genotype-phenotype correlations between CFTR and symptomatic pancreatitis will be
      reviewed. Symptomatic pancreatitis occurs in 20% of pancreatic sufficient CF
      patients. In order to evaluate genotype-phenotype correlations, the Pancreatic
      Insufficiency Prevalence (PIP) score was developed and validated to determine
      severity in a large number of CFTR mutations. Specific CFTR genotypes are
      significantly associated with pancreatitis. Patients who carry genotypes with
      mild phenotypic effects have a greater risk of developing pancreatitis than
      patients carrying genotypes with moderate-severe phenotypic consequences at any
      given time. CONCLUSIONS: The genotype-phenotype correlation in pancreatitis is
      unique compared to other organ manifestations but still consistent with the
      complex monogenic nature of CF. Paradoxically, genotypes associated with
      otherwise mild phenotypic effects have a greater risk for causing pancreatitis;
      compared with genotypes associated with moderate to severe disease phenotypes.
      Greater understanding into the underlying mechanisms of disease is much needed.
      The emergence of CFTR-assist therapies may potentially play a future role in the
      treatment of CFTR-mutation associated pancreatitis.

PMID- 22658666
TI  - Positioner and clothing artifact can affect one-third radius bone mineral density
      measurement.
AB  - This report identifies a radius dual-energy X-ray absorptiometry (DXA) confounder
      and technical approach to avoid this inaccuracy. Initially, a precision study
      revealed substantial differences (p<0.001) in radius bone mineral density (BMD)
      least significant change ranging from 0.038 to 0.073g/cm(2) between 3
      technologists that each performed assessments in 30 men and 30 women.
      Subsequently, visual examination of all 360 forearm DXA images, including bone,
      soft tissue, neutral, and air point-typing was performed. Errors in automated
      "soft tissue" identification were observed; compared with the manufacturer's
      ideal depiction, suboptimal soft tissue point-typing was present in 30/360 scans
      (8.3%) involving 27 individuals. These point-typing deviations appeared to result
      from inclusion of forearm positioner slots at the scan field edges or clothing
      covering the forearm. Twenty-four individuals had a paired scan appropriately
      point-typed, thus allowing evaluation of the effect on BMD measurement. In those
      with incorrect point-typing associated with positioner slots, the mean one-third
      radius BMD was ~7% higher. In conclusion, positioner slots at the edges of the
      distal scan field can lead to automated soft tissue identification inaccuracies
      and consequent erroneous one-third radius BMD measurement. DXA technologists
      should avoid slot inclusion in forearm scans and evaluate point-typing as part of
      routine analysis.

PMID- 22658667
TI  - [Herpes oesophagitis in a patient with Darier's disease].

PMID- 22658668
TI  - Reversible acute chorea in a patient with diabetes treated with hemodialysis.
AB  - Chorea is an abnormal hyperkinetic movement disorder. The reasons for chorea are
      diverse and include hereditary, endocrine, toxic, vascular, infectious,
      autoimmune, and metabolic etiologies. We present a 64-year-old woman with acute
      chorea who suffered from diabetes with recurrent hypoglycemia, and chronic renal
      failure treated by hemodialysis. The full clinical recovery, negative work-up and
      disappearance of basal ganglia lesions on the follow-up imaging emphasize the
      transient character of encephalopathy expressed by acute chorea in patients with
      diabetes treated with hemodialysis.

PMID- 22658669
TI  - Type 2 diabetes and/or its treatment leads to less cognitive impairment in
      Alzheimer's disease patients.
AB  - AIM: To evaluate the cognitive performance of a homogeneous population of
      Alzheimer's disease (AD), non-demented Type 2 Diabetes Mellitus (DIAB), demented
      with concomitant diseases (AD+DIAB) and healthy control subjects. AD is a
      progressive dementia disorder characterized clinically by impairment of memory,
      cognition and behavior. Recently, a major research interest in AD has been placed
      on early evaluation. Diabetes is one of the clinical conditions that represent
      the greatest risk of developing oxidative stress and dementia. Glucose overload,
      leading to the development of impaired-induced insulin secretion in DIAB and has
      been suggested to slow or deter AD pathogenesis. METHODS: The degree of cognitive
      impairment was determined on the Alzheimer Disease Assessment Scale-Cognitive
      (ADAS-Cog) and the Folstein's Mini Mental State Examination (MMSE); the severity
      of dementia was quantified applying the Clinical Dementia Rating (CDR) test; the
      Hamilton test was employed to evaluate depressive conditions; the final
      population studied was 101 subjects. RESULTS: The cognitive deterioration is
      statistically significantly lower (p<0.05) in AD+DIAB patients as compared with
      AD patients. CONCLUSIONS: In this longitudinal study the superimposed diabetic
      condition was associated with a lower rate of cognitive decline, while diabetic
      non-demented patients and controls present normal scores.

PMID- 22658670
TI  - Diabetes prevalence and determinants in adults in China mainland from 2000 to
      2010: a systematic review.
AB  - AIMS: To systematically review trends in diabetes mellitus (DM) prevalence in
      adults in China over the last 10 years and to identify the determinants of these
      trends. METHODS: A systematic search was conducted for studies published between
      2000 and 2010. Studies reporting DM prevalence were included if they met the pre
      determined criteria. The prevalence estimates and reported determinants of these
      studies were compared. RESULTS: Twenty-five manuscripts, reporting on 22 studies,
      were selected for inclusion in the review. There has been an increase in DM
      prevalence from 2.6% to 9.7% in China over the past decade. DM prevalence is
      strongly associated with age and is higher in urban residents compared with rural
      populations. Some studies found a difference in DM prevalence between males and
      females, but this finding was not consistent. Other commonly reported
      associations with DM included family history, obesity and hypertension.
      CONCLUSION: Over the period of 2000-2010, we identify a significant increase in
      DM prevalence at the national level. It is important for all levels of government
      to develop more effective strategies to prevent and manage this rising diabetes
      epidemic. There is also an important need for more large-scale studies of
      diabetes in the western and central regions of China.

PMID- 22658671
TI  - Quality of life improves among post-menopausal women who received bone
      augmentation during dental implant therapy.
AB  - Quality of life outcomes among patients receiving implants have been well
      studied, but little is known about the effects of bone augmentation in this
      therapy. The purpose of this paper was to assess quality of life changes among
      postmenopausal women receiving dental implants with bone augmentation during
      implant therapy. This was a prospective cohort study. 48 patients were recruited
      at the University of Connecticut Health Center and received one of three surgical
      augmentation methods: dehiscence repair; expansion alone; or expansion with
      dehiscence repair. The predictor variable was type of augmentation procedure.
      Quality of life measured by the Oral Health Impact Profile-14 (OHIP-14) was the
      outcome measure and was assessed prior to treatment, 1 week, 8 weeks and 9 months
      after surgery. Changes in OHIP-14 were evaluated by repeated measures analysis of
      variance. The mean initial OHIP-14 scores on total items checked were 4.6
      (SD=3.0) and declined significantly to 2.0 (SD=2.0) at 9 months. The mean
      baseline severity score was 15.4 (SD=8.9) improving significantly to 7.5 (SD=7.6)
      at 9 months. Type of augmentation procedure did not affect quality of life. The
      participants' quality of life improved continuously from the pretreatment to the
      9-month assessment, including improvements 1 week after implant placement.

PMID- 22658672
TI  - Which kind of miniplate to use in mandibular sagittal split osteotomy? An in
      vitro study.
AB  - This study verified the resistance to displacement of six miniplate fixation
      methods after sagittal split osteotomy (SSO). SSO was performed in 30
      polyurethane synthetic mandible replicas. The distal segments were advanced (4
      mm) and specimens were grouped according to the fixation method: four-hole
      standard miniplate; four-hole locking miniplate; six-hole standard miniplate; six
      hole locking miniplate; six-hole standard sagittal miniplate; six-hole locking
      sagittal miniplate. Biomechanical evaluation was performed by applying
      compression loads to three points on the second molar region, using an Instron
      universal testing machine until a 3mm displacement of the segments occurred.
      Compression loads able to produce 3mm displacement were recorded in kN and
      subjected to analysis of variance (P<0.01) and Tukey's tests for comparison
      between groups (P<0.05). The locking sagittal miniplate showed higher resistance
      to displacement than the regular four- and six-hole locking and standard
      miniplates. No significant differences were observed between the locking sagittal
      miniplate and the regular sagittal or the four-hole locking miniplates. Two of
      the three groups with the best results had locking plate fixation methods.
      Fixation of SSO with a single miniplate is better accomplished using six-hole
      locking sagittal miniplates, six-hole standard sagittal miniplates, or four-hole
      locking miniplates; these methods are more resistant to displacement.

PMID- 22658673
TI  - The effect of vitamin C administration on monosodium glutamate induced liver
      injury. An experimental study.
AB  - Monosodium glutamate (MSG) is a commonly used food enhancer. Glutamate is used as
      food additive for enhancing the "meat flavor" of food and gives a particular
      taste named "umami". In this study, we evaluated the effect of vitamin C on
      monosodium glutamate induced rat liver injury. This study was divided into 3
      groups: group 1 received a diet containing 0.9% NaCl; group 2 received diet
      containing MSG 6 mg/g/b.w.; and group 3 received a diet containing 6 mg/g/b.w.
      followed by vitamin C (500 mg/kg/b.w.) for 45 days. The resulting changes were
      detected using histological, histochemical, ultrastructural, and
      immuohistochemical analysis. Severe alterations were recorded including
      dilatations of the central veins; severe cyto-architectural distortions of the
      hepatocytes; marked reduction in both carbohydrates and proteins; vacuolated
      cytoplasm, swollen mitochondria and vesiculated rough endoplasmic reticulum with
      picknotic nuclei; in addition to significant variation in the expression of ki-67
      and p53 proteins. The data obtained from this study showed the improvements in
      the pathological architecture of the liver after treatment with vitamin C. The
      present data point to the ameliorative effect of vitamin C against MSG induced
      liver injury.

PMID- 22658674
TI  - Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
AB  - RNA-binding proteins (RBPs) determine RNA fate from synthesis to decay. Employing
      two complementary protocols for covalent UV crosslinking of RBPs to RNA, we
      describe a systematic, unbiased, and comprehensive approach, termed "interactome
      capture," to define the mRNA interactome of proliferating human HeLa cells. We
      identify 860 proteins that qualify as RBPs by biochemical and statistical
      criteria, adding more than 300 RBPs to those previously known and shedding light
      on RBPs in disease, RNA-binding enzymes of intermediary metabolism, RNA-binding
      kinases, and RNA-binding architectures. Unexpectedly, we find that many proteins
      of the HeLa mRNA interactome are highly intrinsically disordered and enriched in
      short repetitive amino acid motifs. Interactome capture is broadly applicable to
      study mRNA interactome composition and dynamics in varied biological settings.

PMID- 22658675
TI  - Homelessness as culture: How transcultural nursing theory can assist caring for
      the homeless.
AB  - The concepts of culture and homelessness are both complex and contested. This
      paper examines homelessness through the lens of transcultural nursing theory,
      increasing understanding of both homelessness and transcultural theory. We argue
      that homelessness can be usefully conceptualised as a culture and that the
      application of transcultural theory to caring for homeless people will add
      further to the utility of these theories. The application of transcultural theory
      can add to the repertoire of skills the nurse needs to care for not only homeless
      clients, but, for a diverse range of client groups.

PMID- 22658676
TI  - Evaluation of preference for voice prosthesis.

PMID- 22658677
TI  - Impact of age on acute toxicity induced by bio- or chemo-radiotherapy in patients
      with head and neck cancer.
AB  - INTRODUCTION: The purpose of this study is to retrospectively analyze acute
      toxicity encountered in young and old patients treated with chemo-radiation or
      bio-radiation at the S. Croce General Hospital between 1997 and 2008, in daily
      clinical practice. MATERIAL AND METHODS: Three hundred and seventeen patients
      were allocated into two groups according to age (cut-off 65 years). The two
      groups were compared in terms of treatment related toxicities, treatment activity
      and efficacy. Epidermal Growth factor receptor (EGFr), Human papillomavirus (HPV)
      and p53 status were also considered. RESULTS: As expected, overall survival was
      significantly worse in elderly patients (p=0.005), but response rate, including
      complete response rate, was similar between the two age groups, as were most of
      the side effects analyzed. However, infections (p=0.011) and in particular
      pneumonias (p=0.002) were significantly more represented in elderly patients.
      CONCLUSION: Elderly patients treated with chemo-radiation or bio-radiation in our
      centre had a higher risk of infection and in particular, pneumonia. These data
      suggest a more careful follow-up, but age alone does not justify their exclusion
      from treatment.

PMID- 22658678
TI  - Human papillomavirus in oral atrophic lichen planus lesions.
AB  - OBJECTIVES: Oral lichen planus (OLP) is potentially premalignant disorder in
      which human papillomavirus (HPV) DNA is detected more often than in normal oral
      mucosa. We assessed HPV-genotype distribution in atrophic OLPs as related to DNA
      content and repair, proliferation activity, apoptosis, cell adhesion and
      lymphocyte infiltration. MATERIALS AND METHODS: Eighty-two OLP patients (74.4%
      women) with a mean follow-up-time of 62.4 months were included in the study. HPV
      was genotyped with Luminex-based assay detecting 24 HPV-genotypes. Data on a
      panel of biomarkers and static cytometry performed in these samples before were
      compared with HPV data. RESULTS: HPV DNA was found in 15.9% of OLPs with
      genotypes: HPV6/11/16/31/33 and one multiple-type infection. Two of the five
      patients who developed cancer had low-risk HPV6/11 infection while three were HPV
      negative. There was a statistically significant correlation between HPV DNA in
      OLP and DNA content and ploidy markers determined with static cytometry: in HPV
      positive samples, proliferation index was higher (p=0.016), less cells were in
      resting state G1/G0 (p=0.021) but more often in the S-phase (p=0.036) than in HPV
      negative lesions. HPV positivity was also related to topoisomerase IIalpha
      (p=0.051), caspase-3 (p=0.049) and CD20 (p=0.010) protein expression. CONCLUSION:
      HPV-infection is associated with a subgroup of atrophic OLP. Static cytometry is
      a sensitive method to identify HPV-associated changes in DNA content and cell
      proliferation. Of 16 markers, only topoisomerase IIalpha (proliferation and DNA
      repair), caspase-3 (apoptosis) and CD20 (B-lymphocytes) were related to HPV. None
      of the HR-HPVs but only LR-HPVs were associated with the lesions developed to
      cancer.

PMID- 22658679
TI  - Comment on the article "A new classification for potentially malignant disorders
      of the oral cavity" by Sachin C. Sarode et al. Published in Oral Oncology
      47(2011): 920-921.

PMID- 22658680
TI  - Uptake, allocation and signaling of nitrate.
AB  - Plants need to acquire nitrogen (N) efficiently from the soil for growth. Nitrate
      is one of the major N sources for higher plants. Therefore, nitrate uptake and
      allocation are key factors in efficient N utilization. Membrane-bound
      transporters are required for nitrate uptake from the soil and for the inter- and
      intracellular movement of nitrate inside the plants. Four gene families, nitrate
      transporter 1/peptide transporter (NRT1/PTR), NRT2, chloride channel (CLC), and
      slow anion channel-associated 1 homolog 3 (SLAC1/SLAH), are involved in nitrate
      uptake, allocation, and storage in higher plants. Recent studies of these
      transporters or channels have provided new insights into the molecular mechanisms
      of nitrate uptake and allocation. Interestingly, several of these transporters
      also play versatile roles in nitrate sensing, plant development, pathogen
      defense, and/or stress response.

PMID- 22658681
TI  - Unusual cyanobacterial TCA cycles: not broken just different.
AB  - As a fundamental energy-conserving process common to all living organisms,
      respiration is responsible for the oxidation of respiratory substrates to drive
      ATP synthesis. Accordingly, it has long been accepted that a complete
      tricarboxylic acid (TCA) cycle is necessary for respiratory energy production.
      Cyanobacteria, similar to some other prokaryotes, appeared to have an incomplete
      TCA cycle because they lack the enzyme 2-oxoglutarate dehydrogenase (OGDH).
      However, it has recently been reported that the cycle can be completed by the
      action of two alternative enzymes. In this opinion article, we discuss the
      progress being made to elucidate the nature of the TCA cycles in cyanobacteria
      and plants and outline open questions concerning the functional significance of
      this unusual metabolic feature in a broader evolutionary context.

PMID- 22658682
TI  - A scalable and accurate method for classifying protein-ligand binding geometries
      using a MapReduce approach.
AB  - We present a scalable and accurate method for classifying protein-ligand binding
      geometries in molecular docking. Our method is a three-step process: the first
      step encodes the geometry of a three-dimensional (3D) ligand conformation into a
      single 3D point in the space; the second step builds an octree by assigning an
      octant identifier to every single point in the space under consideration; and the
      third step performs an octree-based clustering on the reduced conformation space
      and identifies the most dense octant. We adapt our method for MapReduce and
      implement it in Hadoop. The load-balancing, fault-tolerance, and scalability in
      MapReduce allow screening of very large conformation spaces not approachable with
      traditional clustering methods. We analyze results for docking trials for 23
      protein-ligand complexes for HIV protease, 21 protein-ligand complexes for
      Trypsin, and 12 protein-ligand complexes for P38alpha kinase. We also analyze
      cross docking trials for 24 ligands, each docking into 24 protein conformations
      of the HIV protease, and receptor ensemble docking trials for 24 ligands, each
      docking in a pool of HIV protease receptors. Our method demonstrates significant
      improvement over energy-only scoring for the accurate identification of native
      ligand geometries in all these docking assessments. The advantages of our
      clustering approach make it attractive for complex applications in real-world
      drug design efforts. We demonstrate that our method is particularly useful for
      clustering docking results using a minimal ensemble of representative protein
      conformational states (receptor ensemble docking), which is now a common strategy
      to address protein flexibility in molecular docking.

PMID- 22658683
TI  - The impact of fine-tuning of optical recognition system on database reliability.
AB  - Although optical reading systems are important tools to transfer data from a
      paper form to electronic databases, the impact of system fine-tuning on the final
      error rate is not usually considered. At the end of a multi-step process
      involving paper form design training of operators, and fine-tuning procedure, the
      final rate of error can be reduced from 0.65% to 0.05%. Fine-tuning should be
      introduced as a standard procedure while using optical reading systems.

PMID- 22658685
TI  - Effect of sewage sludge content on gas quality and solid residues produced by
      cogasification in an updraft gasifier.
AB  - In the present work, the gasification with air of dehydrated sewage sludge (SS)
      with 20 wt.% moisture mixed with conventional woody biomass was investigated
      using a pilot fixed-bed updraft gasifier. Attention was focused on the effect of
      the SS content on the gasification performance and on the environmental impact of
      the process. The results showed that it is possible to co-gasify SS with wood
      pellets (WPs) in updraft fixed-bed gasification installations. However, at high
      content of sewage sludge the gasification process can become instable because of
      the very high ash content and low ash fusion temperatures of SS. At an equivalent
      ratio of 0.25, compared with wood pellets gasification, the addition of sewage
      sludge led to a reduction of gas yield in favor of an increase of condensate
      production with consequent cold gas efficiency decrease. Low concentrations of
      dioxins/furans and PAHs were measured in the gas produced by SS gasification,
      well below the limiting values for the exhaust gaseous emissions. NH(3), HCl and
      HF contents were very low because most of these compounds were retained in the
      wet scrubber systems. On the other hand, high H(2)S levels were measured due to
      high sulfur content of SS. Heavy metals supplied with the feedstocks were mostly
      retained in gasification solid residues. The leachability tests performed
      according to European regulations showed that metals leachability was within the
      limits for landfilling inert residues. On the other hand, sulfate and chloride
      releases were found to comply with the limits for non-hazardous residues.

PMID- 22658686
TI  - Methods for fitting a parametric probability distribution to most probable number
      data.
AB  - Every year hundreds of thousands, if not millions, of samples are collected and
      analyzed to assess microbial contamination in food and water. The concentration
      of pathogenic organisms at the end of the production process is low for most
      commodities, so a highly sensitive screening test is used to determine whether
      the organism of interest is present in a sample. In some applications, samples
      that test positive are subjected to quantitation. The most probable number (MPN)
      technique is a common method to quantify the level of contamination in a sample
      because it is able to provide estimates at low concentrations. This technique
      uses a series of dilution count experiments to derive estimates of the
      concentration of the microorganism of interest. An application for these data is
      food-safety risk assessment, where the MPN concentration estimates can be fitted
      to a parametric distribution to summarize the range of potential exposures to the
      contaminant. Many different methods (e.g., substitution methods, maximum
      likelihood and regression on order statistics) have been proposed to fit
      microbial contamination data to a distribution, but the development of these
      methods rarely considers how the MPN technique influences the choice of
      distribution function and fitting method. An often overlooked aspect when
      applying these methods is whether the data represent actual measurements of the
      average concentration of microorganism per milliliter or the data are real-valued
      estimates of the average concentration, as is the case with MPN data. In this
      study, we propose two methods for fitting MPN data to a probability distribution.
      The first method uses a maximum likelihood estimator that takes average
      concentration values as the data inputs. The second is a Bayesian latent variable
      method that uses the counts of the number of positive tubes at each dilution to
      estimate the parameters of the contamination distribution. The performance of the
      two fitting methods is compared for two data sets that represent Salmonella and
      Campylobacter concentrations on chicken carcasses. The results demonstrate a bias
      in the maximum likelihood estimator that increases with reductions in average
      concentration. The Bayesian method provided unbiased estimates of the
      concentration distribution parameters for all data sets. We provide computer code
      for the Bayesian fitting method.

PMID- 22658684
TI  - Beyond the colour of my skin: how skin colour affects the sense of body
      ownership.
AB  - Multisensory stimulation has been shown to alter the sense of body-ownership.
      Given that perceived similarity between one's own body and those of others is
      crucial for social cognition, we investigated whether multisensory stimulation
      can lead participants to experience ownership over a hand of different skin
      colour. Results from two studies using introspective, behavioural and
      physiological methods show that, following synchronous visuotactile (VT)
      stimulation, participants can experience body-ownership over hands that seem to
      belong to a different racial group. Interestingly, a baseline measure of implicit
      racial bias did not predict whether participants would experience the RHI, but
      the overall strength of experienced body-ownership seemed to predict the
      participants' post-illusion implicit racial bias with those who experienced a
      stronger RHI showing a lower bias. These findings suggest that multisensory
      experiences can override strict ingroup/outgroup distinctions based on skin
      colour and point to a key role for sensory processing in social cognition.

PMID- 22658687
TI  - Perioperative use of levosimendan: best practice in operative settings.

PMID- 22658688
TI  - A biocompatible cardiopulmonary bypass strategy to reduce hemostatic and
      inflammatory alterations: a randomized controlled trial.
AB  - OBJECTIVE: Cardiopulmonary bypass (CPB) systems without a venous reservoir rarely
      are adopted clinically. The effects of a biocompatible CPB system with a venous
      reservoir were evaluated on the activation of the coagulation and inflammatory
      systems. DESIGN: A prospective, randomized controlled trial. SETTING: A
      university hospital (single center). PARTICIPANTS: Eighty-three coronary artery
      bypass graft (CABG) surgery patients were assigned to the Physio group (closed
      venous reservoir, phosphorylcholine coating, and no cardiotomy suction) or the
      Standard group (open, noncoated, and cardiotomy suction used). METHODS: Blood
      samples were obtained at 6 different time points before, during, and after
      surgery. Nuclear factor-kB (NF-kappaB) was evaluated before surgery and 2 and 24
      hours after surgery. Myocardial damage was evaluated measuring cardiac troponin
      I. MEASUREMENTS AND MAIN RESULTS: Interleukin (IL)-6 (a marker of inflammation),
      prothrombin fragment 1-2 (PF-1.2, a marker of thrombin generation), plasmin
      antiplasmin complex (PAP, a marker of fibrinolysis), and platelet factor 4 (PF4,
      a marker of platelet activation) were measured. The DNA binding activity of
      proinflammatory transcription factor NF-kappaB was quantified in the isolated
      lymphomonocyte cells. Surgery caused changes of all plasma biomarkers. This
      reaction was attenuated strongly in the Physio group; PF-1.2, PAP, and PF4 all
      were decreased significantly. In the Physio group, a significantly lower cardiac
      troponin I release was observed postoperatively. After surgery, NF-kappaB
      activity was reduced in the Physio group although this difference was not
      statistically significant. CONCLUSIONS: A multimodal strategy using a closed and
      phosphorylcholine-coated CPB circuit together with the avoidance of cardiotomy
      suction reduced activation of the coagulation and fibrinolytic systems
      intraoperatively, although these changes did not persist postoperatively.
      However, no difference in clinical outcome was appreciated on a larger scale.

PMID- 22658689
TI  - Myocardial bridging assessed by multidetector computed tomography: likely cause
      of chest pain in younger patients with low prevalence of dyslipidemia.
AB  - INTRODUCTION AND OBJECTIVES: The relationship between myocardial bridging and
      symptoms is still unclear. The purpose of our study was to assess the
      relationship between myocardial bridging detected by multidetector computed
      tomography and symptoms in a patient population with chest pain syndrome.
      METHODS: The study enrolled 393 consecutive patients without previous coronary
      artery disease studied for chest pain and referred to multidetector computed
      tomography between January 2007 and December 2010. Noninvasive coronary
      angiography was performed using multidetector computed tomography. Myocardial
      bridging was defined as part of a coronary artery completely surrounded by
      myocardium on axial and multiplanar reformatted images. RESULTS: Mean age was
      64.6 (12.4) years and 44.8% were male. Multidetector computed tomography detected
      86 myocardial bridging images in 82 of the 393 patients (20.9%). Left anterior
      descending was the most frequent coronary artery involved (87.2%). The prevalence
      of myocardial bridging was significantly higher in patients without significant
      atherosclerotic coronary stenosis on multidetector computed tomography (24.9% vs
      15.0%; P=.02). Patients with myocardial bridging were younger (60.3 [13.8] vs
      65.8 [11.9]; P<.001), had less prevalence of hyperlipidemia (29.3% vs 41.8%;
      P=.03), and more prevalence of cardiomyopathy (6.1% vs 1.6%, P=.02) compared with
      patients without myocardial bridging on multidetector computed tomography.
      CONCLUSIONS: Multidetector computed tomography is an easy and reliable tool for
      comprehensive in vivo diagnosis of myocardial bridging. The results of the
      present study suggest myocardial bridging is the cause of chest pain in a
      subgroup of younger aged patients with less prevalence of hyperlipidemia and more
      prevalence of cardiomyopathy than patients with significant atherosclerotic
      coronary artery disease on multidetector computed tomography. Full English text
      available from:www.revespcardiol.org.

PMID- 22658690
TI  - Utilization of evidence-based cardiovascular therapies and achievement of
      therapeutic goals in patients with peripheral artery disease.
AB  - INTRODUCTION AND OBJECTIVES: Patients with peripheral artery disease have a high
      risk of cardiovascular events and death. The rate of prescription of evidence
      based cardiovascular therapies and the attainment of therapeutic goals in this
      population is suboptimal. There are no previous studies evaluating the rate of
      prescription of these therapies in our country. METHODS: PERIFERICA is a cross
      sectional study conducted from May to December 2009 in 440 outpatient clinics of
      general practitioners, internal medicine, cardiology, vascular surgery,
      endocrinology, and nephrology specialists throughout Spain. Subjects were
      included if they were aged >=45 years and had peripheral artery disease and a
      blood sample obtained during the previous 6 months. Patients were excluded if
      they had coronary or cerebrovascular diseases. Clinical and anthropometric
      variables and blood analysis were obtained in all participants. RESULTS: In
      total, 4087 patients were included in the study (mean age, 68 years; 74% men).
      There was a high prevalence of diabetes (50%) and hypertension (90%); 79% of
      participants received lipid-lowering drugs (76% statins), 85.5% antihypertensive
      drugs (66% renin-angiotensin blockers) and 83% antithrombotics (75% antiplatelet
      drugs and 11% anticoagulants). In addition, 30% of subjects had a low-density
      lipoprotein cholesterol concentration n<100 mg/dL, 29.5% had optimal control of
      blood pressure, and 74.5% did not smoke. Only 8% had a good control of all of
      their cardiovascular risk factors. CONCLUSIONS: Although a high percentage of
      subjects with peripheral artery disease receives adequate treatment with evidence
      based preventive therapies, the percentage of subjects with good control of all
      their risk factors is low.

PMID- 22658691
TI  - Metabolic autopsy with postmortem cultured fibroblasts in sudden unexpected death
      in infancy: diagnosis of mitochondrial respiratory chain disorders.
AB  - Mitochondrial respiratory chain disorders are the most common disorders among
      inherited metabolic disorders. However, there are few published reports regarding
      the relationship between mitochondrial respiratory chain disorders and sudden
      unexpected death in infancy. In the present study, we performed metabolic autopsy
      in 13 Japanese cases of sudden unexpected death in infancy. We performed fat
      staining of liver and postmortem acylcarnitine analysis. In addition, we analyzed
      mitochondrial respiratory chain enzyme activity in frozen organs as well as in
      postmortem cultured fibroblasts. In heart, 11 cases of complex I activity met the
      major criteria and one case of complex I activity met the minor criteria. In
      liver, three cases of complex I activity met the major criteria and four cases of
      complex I activity met the minor criteria. However, these specimens are
      susceptible to postmortem changes and, therefore, correct enzyme analysis is hard
      to be performed. In cultured fibroblasts, only one case of complex I activity met
      the major criteria and one case of complex I activity met the minor criteria.
      Cultured fibroblasts are not affected by postmortem changes and, therefore,
      reflect premortem information more accurately. These cases might not have been
      identified without postmortem cultured fibroblasts. In conclusion, we detected
      one probable case and one possible case of mitochondrial respiratory chain
      disorders among 13 Japanese cases of sudden unexpected death in infancy.
      Mitochondrial respiratory chain disorders are one of the important inherited
      metabolic disorders causing sudden unexpected death in infancy. We advocate
      metabolic autopsy with postmortem cultured fibroblasts in sudden unexpected death
      in infancy cases.

PMID- 22658692
TI  - Outcome of infants diagnosed with 3-methyl-crotonyl-CoA-carboxylase deficiency by
      newborn screening.
AB  - INTRODUCTION: 3-Methyl CoA carboxylase (3-MCC) deficiency is an inborn error of
      metabolism in the catabolism of the amino acid leucine. Original reports
      suggested this disorder was associated with significant neurological and
      biochemical effects. However newborn screening has identified a higher than
      expected incidence of this disorder with apparent normal outcome in most cases.
      METHOD: A retrospective analysis of thirty-five cases of 3-MCC deficiency
      identified by newborn screening and diagnosed by enzyme or molecular analysis.
      RESULTS: There was a strong inverse correlation between initial C5OH level and
      residual enzyme activity. A few reports of hypoglycemia, ketosis, poor
      feeding/failure to thrive or fasting intolerance were reported, but there was no
      clear relationship between symptoms and residual enzyme activity. Developmental
      outcome included several children with mental retardation (including one with
      Down syndrome and one with schizencephaly) and two with Autism Spectrum disorders
      but there was no apparent relationship to residual enzyme activity. Free
      carnitine deficiency was relatively common. DISCUSSION: Although residual enzyme
      activity was clearly related to metabolite elevation, there was no apparent
      relationship with other measures of outcome. The number of reports of neurologic
      abnormalities or metabolic symptoms (poor feeding, hypoglycemia, fasting
      intolerance, etc.) is concerning, but the significance is unclear in this
      retrospective sample.

PMID- 22658693
TI  - Design and synthesis of prodrugs of the rat selective toxicant norbormide.
AB  - Norbormide [5-(alpha-hydroxy-alpha-2-pyridylbenzyl)-7-(alpha-2
      pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but
      infrequently used rodenticide, is known to be uniquely toxic to rats but
      relatively harmless to other rodents and mammals. However, one major drawback of
      NRB as a viable rodenticide relates to an evolutionary aversion developed by the
      rat leading to sub-lethal dosing due to either its unpleasant 'taste' or rapid
      onset of effects. A series of NRB prodrugs were prepared in an effort to 'mask'
      this acute response. Their synthesis and biological evaluation (in vitro
      vasoconstrictory activity, in vitro hydrolytic and enzymatic stability and
      lethality/palatability in vivo) is described. Compound 19 displayed the most
      promising profile with respect to a delay in the onset of symptoms and was
      subsequently demonstrated to be significantly more palatable to rats.

PMID- 22658694
TI  - Clinical significance of the measurements of urinary liver-type fatty acid
      binding protein levels in patients with acute coronary syndrome.
AB  - BACKGROUND: Recently, much attention has been focused on cardio-renal
      interaction. Urinary liver-type fatty acid binding protein (U-L-FABP), which is
      produced in the proximal tubule by renal hypoxia and oxidative stress, has been
      identified as a useful marker for diagnosis of acute kidney disease and a
      predictor of future events in chronic kidney disease. However, the clinical
      significance of U-L-FABP measurements in patients with acute coronary syndrome
      (ACS) has not been completely evaluated. METHODS AND RESULTS: This study included
      50 consecutive patients with ACS [37 with acute myocardial infarction (AMI) and
      13 with unstable angina pectoris (UAP)] and 47 subjects without coronary artery
      disease (control group). U-L-FABP levels, urinary albumin (U-Alb), and other
      serum parameters were measured at admission and at 24 h after percutaneous
      coronary intervention. RESULTS: U-L-FABP levels in patients with AMI were
      significantly higher (p=0.0019), than in control subjects, while patients with
      UAP did not exhibit such an increase. U-L-FABP levels at admission were
      positively correlated with brain natriuretic protein levels (p=0.001) and
      duration of hospitalization (p=0.025). At follow-up angiography, patients with
      restenosis had significantly higher U-L-FABP (p=0.047) and U-Alb levels
      (p<0.0001) than those without restenosis. After a median follow-up of 42 months,
      U-L-FABP levels at second measurement in patients with major adverse
      cardiocerebrovascular events (MACCEs) were significantly higher than those in
      patients without MACCEs (p=0.028). After adjusting for confounding factors, high
      U-L-FABP levels at second measurement were found to be independent factors for
      MACCEs (p=0.019). CONCLUSIONS: These data suggest that patients with ACS,
      especially those with AMI, have high U-L-FABP levels, and that U-L-FABP
      measurements may be useful in identifying high-risk patients for future
      cardiovascular events after ACS.

PMID- 22658695
TI  - Predictive ability of granzyme B for cardiovascular disease and its direction in
      change.

PMID- 22658696
TI  - Comparison of inflammatory markers between diabetic and nondiabetic ST segment
      elevation myocardial infarction.
AB  - BACKGROUND: Inflammation plays a significant role in acute coronary syndrome
      (ACS) and type 2 diabetes mellitus (DM). There may be similar inflammatory
      changes in non-DM patients with ST elevation myocardial infarction (STEMI) and DM
      patients with stable angina (SA), and DM patients with STEMI may have more severe
      changes than the former two groups. The objectives of this study were to
      investigate whether the level of inflammation was similar in patients with non-DM
      STEMI and DM SA, and to evaluate whether the changes in the level of inflammation
      were more severe in patients with DM STEMI compared to the other two groups.
      METHODS AND RESULTS: A variety of inflammatory markers including: highly
      sensitive C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR),
      interleukin-6 (IL-6), IL-18, vascular cell adhesion molecule-1 (VCAM-1), and
      matrix metallopeptidase-9 (MMP-9) as well as insulin resistance were compared
      among the three groups: DM STEMI (90 patients), DM SA (91 patients), and non-DM
      STEMI (76 patients). Inflammatory marker levels were not significantly different
      between the DM SA and non-DM STEMI groups. However, hsCRP and IL-6 were increased
      in the DM STEMI compared to the DM SA patients (p=0.005 and p=0.004,
      respectively). In addition, hsCRP, ESR, and IL-18 were increased in the DM STEMI
      compared to the non-DM STEMI patients (p=0.017, p=0.020, and p=0.033,
      respectively). Furthermore, the fasting insulin and the homeostasis model
      assessment were significantly increased in the DM STEMI compared to the DM SA
      patients (p=0.04 and p=0.004, respectively). CONCLUSIONS: DM SA and non-DM STEMI
      may have similar inflammatory changes. DM STEMI may be a more severe inflammatory
      condition compared to patients with DM SA or non-DM STEMI.

PMID- 22658697
TI  - Use of preprocedural multidetector computed tomography to decrease atrial
      fibrillation recurrence following extensive encircling circumferential pulmonary
      vein isolation.
AB  - BACKGROUND: Myocardial thickness is particularly thick at the ridge between the
      left pulmonary vein (PV) and the left atrial appendage (LAA) by dissection. We
      investigated whether atrial fibrillation (AF) ablation outcome was influenced by
      altering ablation strategies according to the thickness of the PV-LAA ridge using
      preprocedural multidetector computed tomography (MDCT). METHODS AND RESULTS:
      Patients with AF scheduled for extensive encircling circumferential pulmonary
      vein isolation (EEPVI) (110 patients) were divided into 2 groups. In the
      nonmodulation group (32 patients), EEPVI lines were created using a 3.5-mm tip
      irrigated catheter at a maximum power of 30 W for 20-30 s at each site. In the
      modulation group (78 patients), ablation was extended (40-60 s) at the PV-LAA
      ridge if its thickness was >4.0 mm on MDCT examination. Extended ablation at the
      PV-LAA ridge was noted in 37 patients in the modulation group. During 25+/-9
      months of follow-up, recurrence was significantly less in the modulation group
      than in the nonmodulation group (10% vs. 28%; p=0.018). Logistic regression
      analysis showed that modifications in the ablation time and left atrium volume
      index were independent predictors of arrhythmia-free recovery after ablation.
      CONCLUSIONS: Recurrence following EEPVI could be reduced by modifications in the
      ablation time at the PV-LAA ridge.

PMID- 22658698
TI  - P-wave parameters and cardiac repolarization indices: does menopausal status
      matter?
AB  - BACKGROUND AND PURPOSE: Data regarding electrocardiographic characteristics of
      postmenopausal women are lacking. In this prospective, cross-sectional study,
      electrocardiographic P-wave parameters and cardiac repolarization indices of age
      matched pre- and postmenopausal healthy women were compared. We hypothesized that
      menopausal status would have a significant effect on cardiac electrical activity
      and hence electrocardiography (ECG) recordings. MATERIALS AND METHODS: Twelve
      lead ECG recordings were obtained from 125 consecutively recruited postmenopausal
      healthy women aged between 44 and 54 years. The control group consisted of 125
      age-matched premenopausal women. P-wave parameters and cardiac repolarization
      indices were measured and compared with respect to menopausal status. RESULTS:
      Demographic features of premenopausal and postmenopausal women were comparable.
      There were no significant differences between two groups regarding mean values of
      heart rate, maximum and minimum P-wave duration, P-wave dispersion, maximum and
      minimum QT interval, and QT dispersion. Mean values of QT interval obtained from
      lead V5 were also similar. Corrected values which were calculated according to
      Bazett and Fridericia formulas also did not differ between the groups. Mean
      values of Tpeak to Tend (TpTe) (p<0.001) and corrected TpTe (p=0.001) intervals
      obtained from lead V5 were significantly shorter in postmenopausal women when
      compared to those without menopause. CONCLUSION: Tpeak to Tend interval decreased
      significantly while QT intervals and P-wave parameters did not change in
      postmenopausal women when compared to premenopausal women. Association of these
      findings with changes in levels of sex steroids and their prognostic implications
      need to be elucidated with further studies.

PMID- 22658699
TI  - Effect of pitavastatin treatment on changes of plaque volume and composition
      according to the reduction of high-sensitivity C-reactive protein levels.
AB  - BACKGROUND: There are few data regarding the effect of statins on regression and
      compositional changes of plaque according to the reduction in high-sensitivity C
      reactive protein (hs-CRP) levels in acute myocardial infarction (AMI) patients.
      METHODS: We used serial virtual histology-intravascular ultrasound to assess the
      efficacy of pitavastatin (dosage: 2mg/day) on plaque regression and compositional
      changes according to the degree of reduction in hs-CRP levels from baseline to
      follow-up [>=1mg/dl (n=62) vs. <1mg/dl (n=32)] in non-intervened non-infarct
      related artery in AMI patients who were enrolled in the Livalo in acute
      myocardial infarction study (LAMIS). RESULTS: Total atheroma and percent atheroma
      volumes decreased more significantly in patients with reduction in hs-CRP
      >=1mg/dl compared with those with reduction in hs-CRP <1mg/dl (-1.7+/-12.4mm(3)
      vs. +2.7+/-7.8mm(3), p<0.015, and -0.4+/-3.4% vs. +0.4+/-4.8%, p<0.001,
      respectively). Absolute and %necrotic core volumes decreased more significantly
      in patients with reduction in hs-CRP >=1mg/dl compared with those with reduction
      in hs-CRP <1mg/dl (-0.4+/-3.5mm(3) vs. +1.9+/-3.4mm(3), p=0.038, and -1.1+/-4.9%
      vs. +2.7+/-4.7%, p=0.016, respectively). Reduction in hs-CRP >=1mg/dl at follow
      up was the independent predictor of reduction of percent atheroma volume and
      %necrotic core volume at follow-up [odds ratio (OR), 2.228; 95% confidence
      interval (CI), 1.390-2.977, p=0.016, and OR, 2.204; 95% CI, 1.512-2.916, p=0.020,
      respectively]. CONCLUSIONS: Reduction in hs-CRP levels in AMI patients plays an
      important role in the beneficial effects of statins on the regression and
      compositional change of coronary plaque.

PMID- 22658700
TI  - Myosin heavy chain composition of the human sternocleidomastoid muscle.
AB  - The sternocleidomastoid (SCM) muscle is one of the neck muscles responsible for
      head posture and control of head movement. It functions in rotation, inclination,
      protraction, extension and flexion of the head, whilst chewing and in exerting
      increased respiratory efforts. This study is the first one describing the myosin
      heavy chain (MyHC) isoform composition of the SCM muscle of presumably healthy
      young males for the purpose of better understanding the contractile properties of
      the muscle as well as to help in evaluation of pathologically altered structure
      of the muscle. Autopsy samples were processed immunohistochemically to reveal the
      MyHC isoform composition. The muscle fibres expressed MyHC-1 (31.5%), -2a (29.7%)
      and -2x (4.3%) or co-expressed MyHC-2a with MyHC-2x (26.8%), MyHC-1 with MyHC-2a
      (4.1%) and/or MyHC-1, -2a with -2x (1.1%). In addition to the MyHC isoforms,
      characteristic of adult limb muscles, a very low percentage of muscle fibres (0.2
      2.7%) expressed MyHC-neo, which is normally not found in adult limb muscles. Only
      two samples exhibited MyHC-neo at a rather higher percentage (6.3% and 7.5%) of
      muscle fibres. The high share of hybrid fibres and the presence of MyHC-neo in
      the SCM muscle differ from that of adult limb muscles where hybrid fibres are
      rare and the expression of immature MyHC isoforms occurs only in pathological or
      experimental conditions. Since the SCM muscle shares the same embryogenic
      potential as limb muscles, its distinct MyHC expression appears to be associated
      with twin innervation and with the intrinsic specialisation to perform multiple
      functions.

PMID- 22658701
TI  - Properties of probiotic bacteria explored by proteomic approaches.
AB  - The study of health-beneficial effects that probiotic bacteria can exert on
      humans and animals is at its beginning. Pending scientific questions include the
      identification of molecular markers of the health-promoting activity of specific
      strains, which may be used to select novel probiotic strains and to gain
      understanding of the mechanisms underlying their effects. In that perspective,
      the role of bacterial proteins must be evaluated, placing proteomics-based
      approaches at the core of the field. Until now, most proteomic analyses focused
      on the dynamics of abundant cytoplasmic proteins during adaptation of bacteria to
      conditions mimicking the gastro-intestinal tract environment. The development of
      in silico and experimental procedures allowing identification and quantification
      of surface-exposed and secreted proteins should boost our understanding of
      bacteria-host crosstalk.

PMID- 22658703
TI  - How to build a pathogen detector: structural basis of NB-LRR function.
AB  - Many plant disease resistance (R) proteins belong to the family of nucleotide
      binding-leucine rich repeat (NB-LRR) proteins. NB-LRRs mediate recognition of
      pathogen-derived effector molecules and subsequently activate host defence. Their
      multi-domain structure allows these pathogen detectors to simultaneously act as
      sensor, switch and response factor. Structure-function analyses and the recent
      elucidation of the 3D structures of subdomains have provided new insight in how
      these different functions are combined and what the contribution is of the
      individual subdomains. Besides interdomain contacts, interactions with
      chaperones, the proteasome and effector baits are required to keep NB-LRRs in a
      signalling-competent, yet auto-inhibited state. In this review we explore
      operational models of NB-LRR functioning based on recent advances in
      understanding their structure.

PMID- 22658702
TI  - Methylphenidate for gait hypokinesia and freezing in patients with Parkinson's
      disease undergoing subthalamic stimulation: a multicentre, parallel, randomised,
      placebo-controlled trial.
AB  - BACKGROUND: Despite optimum medical management, many patients with Parkinson's
      disease are incapacitated by gait disorders including freezing of gait. We aimed
      to assess whether methylphenidate--through its combined action on dopamine and
      noradrenaline reuptake--would improve gait disorders and freezing of gate in
      patients with advanced Parkinson's disease without dementia who also received
      subthalamic nucleus stimulation. METHODS: This multicentre, parallel, double
      blind, placebo-controlled, randomised trial was done in 13 movement disorders
      departments in France between October, 2009, and December, 2011. Eligible
      patients were younger than 80 years and had Parkinson's disease, severe gait
      disorders, and freezing of gate despite optimised treatment of motor fluctuations
      with dopaminergic drugs and subthalamic stimulation. We randomly assigned
      patients (1:1 with a computer random-number generator in blocks of four) to
      receive methylphenidate (1 mg/kg per day) or placebo capsules for 90 days.
      Patients, their carers, study staff, investigators, and data analysts were masked
      to treatment allocation. To control for confounding effects of levodopa we
      assessed patients under standardised conditions with an acute levodopa challenge.
      Our primary outcome was a change in the number of steps during the stand-walk-sit
      (SWS) test without levodopa. We compared the respective mean numbers of steps at
      day 90 in the methylphenidate and placebo groups in a covariance analysis and
      adjusted for baseline differences. This trial is registered with
      ClinicalTrials.gov, number NCT00914095. FINDINGS: We screened 81 patients and
      randomly assigned 35 to receive methylphenidate and 34 to receive placebo. 33
      patients in the methylphenidate group and 32 patients in the placebo group
      completed the study. Efficacy outcomes were assessed in the patients who
      completed the study. Compared with patients in the placebo group (median 33 steps
      [IQR 26-45]), the patients in the methylphenidate group made fewer steps at 90
      days (31 [26-42], F((1, 62))=6.1, p=0.017, adjusted size effect 0.61). Adverse
      events were analysed in all randomly assigned patients. There were significantly
      more adverse events in the methylphenidate group compared with placebo. Patients
      on methylphenidate had a significant increase in heart rate (mean 3.6 [SD 7.2]
      beats per min) and decrease in weight (mean 2.2 [SD 1.8] kg) compared with the
      placebo group. INTERPRETATION: Methylphenidate improved gait hypokinesia and
      freezing in patients with advanced Parkinson's disease receiving subthalamic
      nucleus stimulation. Methylphenidate represents a therapeutic option in the
      treatment of gait disorders at the advanced stage of Parkinson's disease. The
      long term risk-benefit balance should be further studied. FUNDING: French
      Ministry of Health and Novartis Pharma.

PMID- 22658704
TI  - Challenges and progress towards understanding the role of effectors in plant
      fungal interactions.
AB  - Both mutualistic and biotrophic pathogenic fungi rely on living host plants for
      growth and reproduction and must modify host cell structure and function for
      successful infection. The deployment of a diverse set of secreted virulence
      determinants referred to as 'effectors', many of which are directly delivered
      into the host cell, is postulated to be the key to host infection. This review
      provides a snapshot of the current progress in fungal effector biology. Recent
      genome sequencing of rust and powdery mildew obligate biotrophs has provided
      insight into the repertoires of potential effectors of these highly specialised
      pathogens. Identification of the first host-translocated effectors from
      mutualistic fungi has revealed that these fungi also manipulate host cells
      through effectors. The biological activities of some fungal effectors are just
      beginning to be revealed, while much uncertainty still surrounds the mechanisms
      of transport into host cells.

PMID- 22658705
TI  - WITHDRAWN: Loss of neural recognition molecule NB-3 delays the normal projection
      and terminal branching of developing corticospinal tract axons in the mouse.
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- 22658706
TI  - The neural network sustaining crossmodal integration is impaired in alcohol
      dependence: an fMRI study.
AB  - INTRODUCTION: Crossmodality (i.e., the integration of stimulations coming from
      different sensory modalities) is a crucial ability in everyday life and has been
      extensively explored in healthy adults. Still, it has not yet received much
      attention in psychiatry, and particularly in alcohol-dependence. The present
      study investigates the cerebral correlates of crossmodal integration deficits in
      alcohol-dependence to assess whether these deficits are due to the mere
      accumulation of unimodal impairments or rather to specific alterations in
      crossmodal areas. METHODS: Twenty-eight subjects [14 alcohol-dependent subjects
      (ADS), 14 paired controls] were scanned using fMRI while performing a
      categorization task on faces (F), voices (V) and face-voice pairs (FV). A
      subtraction contrast [FV-(F+V)] and a conjunction analysis [(FV-F) ? (FV-V)]
      isolated the brain areas specifically involved in crossmodal face-voice
      integration. The functional connectivity between unimodal and crossmodal areas
      was explored using psycho-physiological interactions (PPI). RESULTS: ADS
      presented only moderate alterations during unimodal processing. More centrally,
      in the subtraction contrast and conjunction analysis, they did not show any
      specific crossmodal brain activation while controls presented activations in
      specific crossmodal areas (inferior occipital gyrus, middle frontal gyrus,
      superior parietal lobule). Moreover, PPI analyses showed reduced connectivity
      between unimodal and crossmodal areas in alcohol-dependence. CONCLUSIONS: This
      first fMRI exploration of crossmodal processing in alcohol-dependence showed a
      specific face-voice integration deficit indexed by reduced activation of
      crossmodal areas and reduced connectivity in the crossmodal integration network.
      Using crossmodal paradigms is thus crucial to correctly evaluate the deficits
      presented by ADS in real-life situations.

PMID- 22658707
TI  - Negative motor phenomena in cortical stimulation: implications for inhibitory
      control of human action.
AB  - Electrical stimulation of the human cortex typically elicits positive
      sensorimotor effects. However, many neurosurgical studies have also reported
      negative motor areas (NMAs) in which stimulation produces inhibition of ongoing
      movement. The neurocognitive implications of these studies have not been
      systematically explored. Here we review the neurosurgical literature on NMAs and
      link this to cognitive mechanisms of inhibition and their role in voluntary
      control of action. In particular, we discuss the functional validity of NMAs. We
      contest the sceptical view that negative effects following stimulation merely
      reflect disruption of positive motor areas. Instead, we suggest that NMAs may
      produce an inhibitory mechanism under ecologically valid conditions.

PMID- 22658710
TI  - The use of bromadiolone to potentiate self-mutilatory bleeding: a case report.

PMID- 22658711
TI  - Mini-dose single-shot spinal anesthesia for cesarean delivery: for whom the bell
      shaped curve tolls.

PMID- 22658709
TI  - Resin zirconia bonding promotion with some novel coupling agents.
AB  - OBJECTIVES: To evaluate and compare three novel coupling agents: 2-hydroxyethyl
      methacrylate, itaconic acid and oleic acid to two silane coupling agents, one
      commercial silane product and 3-acryloxypropyltrimethoxysilane on the bond
      durability of resin composite to zirconia. METHODS: Zirconia samples were silica
      coated by air abrasion and each of the five coupling agents was then applied to
      give five test groups. Resin composite stubs were bonded onto the conditioned
      zirconia surfaces. The samples were stored: dry storage, 30 days in water and
      thermocycled to give a total of fifteen test groups. The shear bond strengths
      were determined using a universal testing machine and data analyzed by two-way
      ANOVA and Tukey HSD (p<0.05) with shear bond strength as dependent variable and
      storage condition and primers as independent variables. The bond formation of the
      five coupling agents to zirconia was examined by X-ray photoelectron spectroscopy
      (XPS). RESULTS: Two-way ANOVA analysis showed that there was a significant
      difference for different primers (p<0.05) and different storage conditions
      (p<0.05) on the shear bond strength values measured. XPS analysis showed a shift
      in binding energy for O(1s) after priming with the five coupling agents which
      revealed different bond formations related to the functional groups of the
      coupling agents. SIGNIFICANCE: The shear bond strength values measured for all
      coupling agents after water storage and thermocycling exceed the minimum shear
      bond strength value of 5MPa set by ISO. The silane coupling agent, 3
      acryloxypropyltrimethoxysilane, showed the highest bond strength of the three
      storage conditions.

PMID- 22658708
TI  - Efficacy of transcranial magnetic stimulation targets for depression is related
      to intrinsic functional connectivity with the subgenual cingulate.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) to the left dorsolateral
      prefrontal cortex (DLPFC) is used clinically for the treatment of depression.
      However, the antidepressant mechanism remains unknown and its therapeutic
      efficacy remains limited. Recent data suggest that some left DLPFC targets are
      more effective than others; however, the reasons for this heterogeneity and how
      to capitalize on this information remain unclear. METHODS: Intrinsic (resting
      state) functional magnetic resonance imaging data from 98 normal subjects were
      used to compute functional connectivity with various left DLPFC TMS targets
      employed in the literature. Differences in functional connectivity related to
      differences in previously reported clinical efficacy were identified. This
      information was translated into a connectivity-based targeting strategy to
      identify optimized left DLPFC TMS coordinates. Results in normal subjects were
      tested for reproducibility in an independent cohort of 13 patients with
      depression. RESULTS: Differences in functional connectivity were related to
      previously reported differences in clinical efficacy across a distributed set of
      cortical and limbic regions. Dorsolateral prefrontal cortex TMS sites with better
      clinical efficacy were more negatively correlated (anticorrelated) with the
      subgenual cingulate. Optimum connectivity-based stimulation coordinates were
      identified in Brodmann area 46. Results were reproducible in patients with
      depression. CONCLUSIONS: Reported antidepressant efficacy of different left DLPFC
      TMS sites is related to the anticorrelation of each site with the subgenual
      cingulate, potentially lending insight into the antidepressant mechanism of TMS
      and suggesting a role for intrinsically anticorrelated networks in depression.
      These results can be translated into a connectivity-based targeting strategy for
      focal brain stimulation that might be used to optimize clinical response.

PMID- 22658712
TI  - Severe glottic stenosis in a parturient with ectodermal dysplasia.
AB  - Airway stenosis in pregnancy is challenging and the literature does not offer
      consensus regarding its evaluation and anesthetic management. A 21-year-old
      nulliparous woman with ectodermal dysplasia and severe glottic stenosis was
      referred to the obstetric anesthesia team for evaluation and peripartum
      management recommendations. She had a history of a congenital complete glottic
      web that required a tracheostomy at birth. After decannulation at age four, she
      was lost to follow-up. On examination in early pregnancy, she was found to have a
      dangerously narrow airway with fixed vocal cords and a glottic aperture of 2-3mm.
      At nine weeks of gestation an elective tracheostomy was performed under local
      anesthesia. She later underwent an uneventful cesarean delivery under spinal
      anesthesia. Ultimately, early interdisciplinary planning for an elective
      tracheostomy helped assure patient safety during advancing pregnancy and
      delivery.

PMID- 22658713
TI  - Type I immune response cytokine-chemokine cascade is associated with pulmonary
      arterial hypertension.
AB  - BACKGROUND: Perivascular infiltrating mononuclear cells have been described in
      the vasculopathy found in multiple types of pulmonary arterial hypertension
      (PAH). We determined the expression of a specific type 1 immune response cytokine
      chemokine cascade-interleukin (IL)-18 -> (monokine induced by gamma-interferon
      [MIG]/chemokine [C-X-C motif] ligand [CXCL] 9, interferon gamma-induced protein
      [IP]-10/CXCL10 and interferon-inducible T-cell alpha chemoattractant
      [ITAC]/CXCL11)-in plasma samples from individuals with World Health Organization
      (WHO) Group 1 PAH. METHODS: We analyzed cytokine and chemokine protein levels in
      plasma from 43 individuals with WHO Group 1 PAH by enzyme-linked immunosorbent
      assay compared with 35 healthy individuals. Immunohistochemical studies on tissue
      specimens from WHO Group 1 PAH patients were performed for cytokines and
      chemokines and their respective receptors. RESULTS: Plasma IL-18 levels from WHO
      Group 1 PAH patients were significantly increased compared with healthy controls.
      Downstream chemokine CXCL10, but not CXCL9 or CXCL11, was markedly elevated
      compared with controls. Cellular sources of IL-18 were medial but not intimal
      smooth muscle cells. IL-18Ralpha was expressed from medial smooth muscle cells,
      endothelial cells, and mononuclear cells. CXCL10 and its main receptor, CXCR3,
      were expressed from infiltrating vascular wall mononuclear cells. CONCLUSIONS:
      These data suggest that augmented expression of IL-18 and CXCL10 may perpetuate
      an inflammatory milieu that eventually contributes to the vascular obstruction
      characteristic of PAH.

PMID- 22658714
TI  - Resting and exercise cerebral blood flow in long-term heart transplant
      recipients.

PMID- 22658715
TI  - Enhanced TKTL1 expression in malignant tumors of the ocular adnexa predicts
      clinical outcome.
AB  - PURPOSE: Malignant tumors metabolize glucose to lactate even in the presence of
      oxygen via the pentose-phosphate pathway. The metabolic switch from oxidative
      glycolysis to nonoxidative fermentation in tumors has been associated with
      overexpression of the transketolase-like-1-gene (TKTL1), which encodes an
      essential and rate-limiting enzyme in the nonoxidative part of the pentose
      phosphate pathway. This study investigates the role of TKTL1 in ocular adnexal
      tumors and analyzes how its expression correlates with the clinical outcomes
      against the background of tumor thickness and mitotic rate. DESIGN: Comparative
      case studies. PARTICIPANTS: We included 89 subjects with malignant tumors of the
      ocular adnexa (44 squamous cell carcinomas, 26 lymphomas, 19 malignant melanomas)
      who had been treated at the University Eye Hospital Freiburg from 1994 to 2008.
      Sixteen subjects with conjunctival nevi, 19 with conjunctival papilloma, and 2
      with conjunctival-reactive lymphoid hyperplasia were included as controls.
      METHODS: TKTL1 expression was assessed by reverse transcriptase-polymerase chain
      reaction and immunohistochemistry and semiquantitatively analyzed using an
      established immunoreactive score (IRS). The tumor recurrence rate, metastasis
      occurrence, and survival time of each patient were assessed retrospectively and
      correlated with the TKTL IRS using Kaplan-Meier and Cox regression analyses. MAIN
      OUTCOME MEASURES: TKTL1 expression, mitotic rate within the tumor mass, and tumor
      thickness and its association with clinical outcome. RESULTS: We identified
      increased TKTL1 protein levels in malignant conjunctival tumors compared with
      control samples and detected an average IRS of 1.78 (standard deviation [SD], +/-
      0.46) for melanomas, 1.3 for lymphomas (SD, +/- 0.79), and 1.22 for squamous cell
      carcinomas (SD, +/- 0. 97) compared with 0.86 for conjunctival nevi (SD, +/-
      0.57) and 0.5 for conjunctival papilloma (SD, +/- 0.83). Multifactorial survival
      analysis showed that TKTL1 overexpression correlated with the patient outcomes in
      malignant tumors (P = 0.045). In the squamous cell carcinomas, tumor thickness
      and mitotic rate correlated more strongly with prognosis compared with TKTL1
      overexpression (P = 0.0061, P = 0.015, and P = 0.061, respectively). CONCLUSIONS:
      TKTL1 is dysregulated in malignant tumors of the ocular adnexa, and enhanced
      expression seems to predict clinical outcome, especially the tumor recurrence
      rate.

PMID- 22658716
TI  - Exposure assessment of boron in Bandirma boric acid production plant.
AB  - Boric acid and sodium borates have been considered as being "toxic to
      reproduction and development", following results of animal studies with high
      doses. Experimentally, a NOAEL of 17.5mg B/kg-bw/day (corresponds to ~2020 ng
      boron/g blood) has been identified for the (male) reproductive effects of boron
      in a multigenerational study of rats, and a NOAEL for the developmental effects
      in rats was identified at 9.6 mg B/kg-bw/day (corresponds to 1270 ng boron/g
      blood). These values are being taken as the basis of current EU safety
      assessments. The present study was conducted to assess the boron exposure under
      extreme exposure conditions in a boric acid production plant located in Bandirma,
      Turkey. The mean blood boron concentrations of low and high exposure groups were
      72.94 +/- 15.43 (48.46-99.91) and 223.89 +/- 60.49 (152.82-454.02)ng/g
      respectively. The mean blood boron concentration of the high exposure group is
      still ~ 6 times lower than the highest no effect level of boron in blood with
      regard to the developmental effects in rats and ~ 9 times lower than the highest
      no effect level of boron in blood with regard to the reprotoxic effects in male
      rats. In this context, boric acid and sodium borates should not be considered as
      toxic to reproduction for humans in daily life.

PMID- 22658717
TI  - Dietary boron: progress in establishing essential roles in human physiology.
AB  - This review summarizes the progress made in establishing essential roles for
      boron in human physiology and assesses that progress in view of criteria for
      essentiality of elements. The evidence to date suggests that humans and at least
      some higher animals may use boron to support normal biological functions. These
      include roles in calcium metabolism, bone growth and maintenance, insulin
      metabolism, and completion of the life cycle. The biochemical mechanisms
      responsible for these effects are poorly understood but the nature of boron
      biochemistry suggests further characterization of the cell signaling molecules
      capable of complexing with boron. Such characterization may provide insights into
      the biochemical function(s) of boron in humans.

PMID- 22658718
TI  - Thyroid function in pregnancy.
AB  - Iodine is required for the production of thyroid hormones. Normal thyroid
      function during pregnancy is important for both the mother and developing fetus.
      This review discusses the changes in thyroid physiology that occur during
      pregnancy, the significance of thyroid function tests and thyroid antibody titers
      assessed during pregnancy, and the potential obstetric complications associated
      with maternal hypothyroidism.

PMID- 22658719
TI  - The toxicology of mercury and its compounds.
AB  - A concentrated review on the toxicology of inorganic mercury together with an
      extensive review on the neurotoxicology of methylmercury is presented. The
      challenges of using inorganic mercury in dental amalgam are reviewed both
      regarding the occupational exposure and the possible health problems for the
      dental patients. The two remaining "mysteries" of methylmercury neurotoxicology
      are also being reviewed; the cellular selectivity and the delayed onset of
      symptoms. The relevant literature on these aspects has been discussed and some
      suggestions towards explaining these observations have been presented.

PMID- 22658720
TI  - Magnetoencephalography in fronto-parietal opercular epilepsy.
AB  - OBJECTIVE: To clarify the clinical and neurophysiological profiles of fronto
      parietal opercular epilepsy in which epileptic spikes are detected with
      magnetoencephalography (MEG) but not with scalp electroencephalography (EEG).
      METHODS: Four patients presented with epileptic spikes localized to the fronto
      parietal opercular cortex, which were only appreciated following MEG recordings.
      RESULTS: In all cases, seizure semiology suggested early activation of the
      operculum and lower peri-rolandic cortex consistent with the somatotopic
      organization of this region, i.e. tingling sensation involving the throat and
      hemi-face or contralateral upper limb, and spasms of the neck and throat. MEG
      spikes were localized in the fronto-parietal operculum. Three of the four
      patients underwent invasive electrocorticography and/or stereo-EEG recordings,
      and spikes were confirmed to arise from the estimated area of MEG dipole
      localization. Two patients remained seizure-free for over 1 year after resection
      of the epileptogenic region; the other patient declined resective surgery due to
      proximity to the language cortex. CONCLUSION: This study demonstrates the
      usefulness of MEG in localizing spikes arising from within the fronto-parietal
      opercular regions, and implies that MEG may provide localizing information in
      patients with symptoms suggestive of opercular epilepsy, even if scalp EEG
      recordings fail to disclose any epileptogenic activities.

PMID- 22658721
TI  - Atl1 regulates choice between global genome and transcription-coupled repair of
      O(6)-alkylguanines.
AB  - Nucleotide excision repair (NER) has long been known to remove DNA lesions
      induced by chemical carcinogens, and the molecular mechanism has been partially
      elucidated. Here we demonstrate that in Schizosaccharomyces pombe a DNA
      recognition protein, alkyltransferase-like 1 (Atl1), can play a pivotal role in
      selecting a specific NER pathway, depending on the nature of the DNA
      modification. The relative ease of dissociation of Atl1 from DNA containing small
      O(6)-alkylguanines allows accurate completion of global genome repair (GGR),
      whereas strong Atl1 binding to bulky O(6)-alkylguanines blocks GGR, stalls the
      transcription machinery, and diverts the damage to transcription-coupled repair.
      Our findings redraw the initial stages of the NER process in those organisms that
      express an alkyltransferase-like gene and raise the question of whether or not
      O(6)-alkylguanine lesions that are poor substrates for the alkyltransferase
      proteins in higher eukaryotes might, by analogy, signal such lesions for repair
      by NER.

PMID- 22658722
TI  - HIPK2 controls cytokinesis and prevents tetraploidization by phosphorylating
      histone H2B at the midbody.
AB  - Failure in cytokinesis, the final step in cell division, by generating tetra- and
      polyploidization promotes chromosomal instability, a hallmark of cancer. Here we
      show that HIPK2, a kinase involved in cell fate decisions in development and
      response to stress, controls cytokinesis and prevents tetraploidization through
      its effects on histone H2B. HIPK2 binds and phosphorylates histone H2B at S14
      (H2B-S14(P)), and the two proteins colocalize at the midbody. HIPK2 depletion by
      targeted gene disruption or RNA interference results in loss of H2B-S14(P) at the
      midbody, prevention of cell cleavage, and tetra- and polyploidization. In HIPK2
      null cells, restoration of wild-type HIPK2 activity or expression of a
      phosphomimetic H2B-S14D derivative abolishes cytokinesis defects and rescues cell
      proliferation, showing that H2B-S14(P) is required for a faithful cytokinesis.
      Overall, our data uncover mechanisms of a critical HIPK2 function in cytokinesis
      and in the prevention of tetraploidization.

PMID- 22658723
TI  - Metabolic enzyme IMPDH is also a transcription factor regulated by cellular
      state.
AB  - Cells need to coordinate gene expression and metabolic state. Inosine
      monophosphate dehydrogenase (IMPDH) controls the guanine nucleotide pool and,
      thereby, cell proliferation. We found that Drosophila IMPDH is also a DNA-binding
      transcriptional repressor. IMPDH attenuates expression of histone genes and E2f,
      a key driver of cell proliferation. Nuclear IMPDH accumulates during the G2 phase
      of the cell cycle or following replicative or oxidative stress. Thus, IMPDH can
      couple the expression of histones and E2F to cellular state. Genome-wide
      profiling and in vitro binding assays established that IMPDH binds sequence
      specifically to single-stranded, CT-rich DNA elements. Surprisingly, this DNA
      binding function is conserved in E. coli IMPDH. The catalytic function of IMPDH
      is not required for DNA binding. Yet substitutions that correspond to human
      retinitis pigmentosa mutations disrupt IMPDH binding to CT-rich, single-stranded
      DNA elements. By doubling as nucleotide biosynthetic enzyme or transcription
      factor, IMPDH can either enable or restrict cell proliferation.

PMID- 22658725
TI  - Is 'forward' the same as 'plus'?...and other adventures in SNP allele
      nomenclature.

PMID- 22658726
TI  - The uncertain road towards genomic medicine.
AB  - Cheap, high-throughput approaches to generating biological data are transforming
      biology into a data-driven science and promise to similarly transform medicine.
      However, the road to genomic medicine is paved with challenges and uncertainty.

PMID- 22658724
TI  - Replication-independent repair of DNA interstrand crosslinks.
AB  - DNA interstrand crosslinks (ICLs) are cytotoxic lesions that covalently link
      opposite strands of the DNA helix and block DNA unwinding. ICLs are repaired
      during and outside S phase, and replication-independent ICL repair (RIR) is
      critical to maintain genomic integrity and to allow transcription in nondividing
      or slowly dividing cells. Here, we show that the Y family DNA polymerase kappa
      (Pol kappa) is essential for RIR of a site-specific ICL lesion in Xenopus egg
      extracts, and that both its catalytic activity and UBZ domains are required for
      this function. We also demonstrate a requirement for PCNA and its modification on
      lysine 164. Finally, we show that Pol kappa participates in ICL repair in
      mammalian cells, particularly in G0. Our results identify key components of the
      RIR pathway and begin to unravel its mechanism.

PMID- 22658727
TI  - Vertical scar versus the inverted-T scar reduction mammaplasty: a 10-year follow
      up.
AB  - A retrospective study was undertaken to evaluate whether the initial outcome of
      two types of reduction mammaplasty techniques (vertical scar reduction
      mammaplasty vs. the inverted-T scar reduction mammaplasty) remains stable in the
      long term: Sixty-nine patients who had undergone breast reduction surgery in the
      period 1997-2000 at the Department of Reconstructive Plastic Surgery at the
      Medical Center of Leeuwarden were willing and able to participate in this study.
      A structured questionnaire was used to assess the degree of patient satisfaction.
      For subjective evaluation, the Strasser Grading System on photographs at the 3
      months after surgery and after long-term follow-up (10 years) was used. The
      median general appreciation mark for the entire surgical procedure given by
      patients was 8 (1-10) on a scale from 1 to 10. Forty-six of the 69 patients could
      be scored according to Strasser: at 3 months in 17 patients (37%) the result was
      'good', in 21 patients (46%) 'mediocre' and in eight patients (17%) 'poor'. After
      10 years, in 37 of the patients (80%) the result was 'good', in six patients
      (13%) 'mediocre' and in three patients (7%) 'poor'. At 3 months, there was a
      higher incidence of bottoming out in the vertical scar group (one on two
      patients) as compared to the inverted-T scar group (one on 10 patients); however,
      at the 10-years follow-up bottoming out was 50% in the inverted-T scar group and
      20% in the vertical scar group. Despite bottoming out, in both the vertical scar
      reduction mammaplasty technique and the inverted-T scar reduction mammaplasty
      technique, high patient satisfaction rates are achieved that remains for years.

PMID- 22658728
TI  - The subcutaneous fat compartments in relation to aesthetically important facial
      folds and rhytides.
AB  - The ideal treatment of the nasolabial fold, the tear trough, the labiomandibular
      fold and the mentolabial sulcus is still discussed controversially. The detailed
      topographical anatomy of the fat compartments may clarify the anatomy of facial
      folds and may offer valuable information for choosing the adequate treatment
      modality. Nine non-fixed cadaver heads in the age range between 72 and 89 years
      (five female and four male) were investigated. Computed tomographic scans were
      performed after injection of a radiographic contrast medium directly into the fat
      compartments surrounding prominent facial folds. The data were analysed after
      multiplanar image reconstruction. The fat compartments surrounding the facial
      folds could be defined in each subject. Different arrangement patterns of the fat
      compartments around the facial rhytides were found. The nasolabial fold, the tear
      trough and the labiomandibular fold represent an anatomical border between
      adjacent fat compartments. By contrast, the glabellar fold and the labiomental
      sulcus have no direct relation to the boundaries of facial fat. Deep fat,
      underlying a facial rhytide, was identified underneath the nasolabial crease and
      the labiomental sulcus. In conclusion, an improvement by a compartment-specific
      volume augmentation of the nasolabial fold, the tear trough and the
      labiomandibular fold is limited by existing boundaries that extend into the skin.
      In the area of the nasolabial fold and the mentolabial sulcus, deep fat exists
      which can be used for augmentation and subsequent elevation of the folds. The
      treatment of the tear trough deformity appears anatomically the most challenging
      area since the superficial and deep fat compartments are separated by an osseo
      cutaneous barrier, the orbicularis retaining ligament. In severe cases, a
      surgical treatment should be considered. By contrast, the glabellar fold shows
      the most simple anatomical architecture. The fold lies above one subcutaneous fat
      compartment that can be used for augmentation.

PMID- 22658729
TI  - From military service to occupational health nursing practice.

PMID- 22658730
TI  - Occupational health nursing around the world.

PMID- 22658731
TI  - The Gulf Cooperation Council.
AB  - The Gulf Cooperation Council was formed in 1981 to create economic, scientific,
      and business cooperation among its members. The opportunity exists for scientific
      collaboration on nursing education, practice, and research.

PMID- 22658732
TI  - Negotiation without confrontation.
AB  - Negotiation does not have to be a test of wills. By adhering to a few simple
      principles, occupational health nurses can turn a potential contest into a
      productive cooperation.

PMID- 22658733
TI  - Prevalence of blood pressure self-monitoring, medication adherence, self
      efficacy, stage of change, and blood pressure control among municipal workers
      with hypertension.
AB  - Despite the availability of effective medications, hypertension remains
      inadequately managed in the United States. It has been established that
      medication adherence is a major strategy for controlling blood pressure. Combined
      interventions to promote adherence are promising, but further research is needed
      to understand which behaviors to target. The frequency of self-monitoring of
      blood pressure among municipal workers is unknown, and the literature is limited
      regarding assessing individuals' readiness and confidence to engage in medication
      adherence. The purpose of this study was to determine the prevalence of
      medication adherence, readiness, self-efficacy, self-monitoring of blood
      pressure, and blood pressure control among hypertensive municipal workers. The
      study population was enrolled in a wellness program established more than 20
      years ago to promote health and safety for a work force in a large southeastern
      U.S. city. The majority of the study participants (75.7%) demonstrated controlled
      blood pressure, reported adherence to antihypertensive medication (70%), and self
      monitored blood pressure (70%).

PMID- 22658736
TI  - Feeling sleepy? You are not alone.
AB  - The Centers for Disease Control and Prevention reports that 30% of the nation's
      workers are sleeping less than 6 hours per day.

PMID- 22658734
TI  - Does current scientific evidence support a link between light at night and breast
      cancer among female night-shift nurses? Review of evidence and implications for
      occupational and environmental health nurses.
AB  - Breast cancer is increasingly prevalent in industrialized regions of the world,
      and exposure to light at night (LAN) has been proposed as a potential risk
      factor. Epidemiological observations have documented an increased breast cancer
      risk among female night-shift workers, and strong experimental evidence for this
      relationship has also been found in rodent models. Indirect support for the LAN
      hypothesis comes from studies involving blind women, sleep duration, bedroom
      light levels, and community nighttime light levels. This article reviews the
      literature, discusses possible mechanisms of action, and provides recommendations
      for occupational health nursing research, practice, and education. Research is
      needed to further explore the relationship between exposure to LAN and breast
      cancer risk and elucidate the mechanisms underlying this relationship before
      interventions can be designed for prevention and mitigation of breast cancer.

PMID- 22658737
TI  - Design of high productivity antibody capture by protein A chromatography using an
      integrated experimental and modeling approach.
AB  - An integrated experimental and modeling approach for the design of high
      productivity protein A chromatography is presented to maximize productivity in
      bioproduct manufacture. The approach consists of four steps: (1) small-scale
      experimentation, (2) model parameter estimation, (3) productivity optimization
      and (4) model validation with process verification. The integrated use of process
      experimentation and modeling enables fewer experiments to be performed, and thus
      minimizes the time and materials required in order to gain process understanding,
      which is of key importance during process development. The application of the
      approach is demonstrated for the capture of antibody by a novel silica-based high
      performance protein A adsorbent named AbSolute. In the example, a series of pulse
      injections and breakthrough experiments were performed to develop a lumped
      parameter model, which was then used to find the best design that optimizes the
      productivity of a batch protein A chromatographic process for human IgG capture.
      An optimum productivity of 2.9 kg L-1 day-1 for a column of 5mm diameter and 8.5
      cm length was predicted, and subsequently verified experimentally, completing the
      whole process design approach in only 75 person-hours (or approximately 2 weeks).

PMID- 22658740
TI  - Syria: public health achievements and sanctions.

PMID- 22658738
TI  - Viral population dynamics and virulence thresholds.
AB  - Viral factors and host barriers influence virally induced disease, and
      asymptomatic versus symptomatic infection is governed by a 'virulence threshold'.
      Understanding modulation of virulence thresholds could lend insight into disease
      outcome and aid in rational therapeutic and vaccine design. RNA viruses are an
      excellent system to study virulence thresholds in the context of quasispecies
      population dynamics. RNA viruses have high error frequencies and our
      understanding of viral population dynamics has been shaped by quasispecies
      evolutionary theory. In turn, research using RNA viruses as replicons with short
      generation times and high mutation rates has been an invaluable tool to test
      models of quasispecies theory. The challenge and new frontier of RNA virus
      population dynamics research is to combine multiple theoretical models and
      experimental data to describe viral population behavior as it changes, moving
      within and between hosts, to predict disease and pathogen emergence. Several
      excellent studies have begun to undertake this challenge using novel approaches.

PMID- 22658741
TI  - Acro-osteolysis.

PMID- 22658742
TI  - Image region duplication detection based on circular window expansion and phase
      correlation.
AB  - Region duplication forgery is one of the tampering techniques that are frequently
      used, where a part of an image is copied and pasted into another part of the same
      image. In this paper, a phase correlation method based on polar expansion and
      adaptive band limitation is proposed for region duplication forgery detection.
      Our method starts by calculating the Fourier transform of the polar expansion on
      overlapping windows pair, and then an adaptive band limitation procedure is
      implemented to obtain a correlation matrix in which the peak is effectively
      enhanced. After estimating the rotation angle of the forgery region, a searching
      algorithm in the sense of seed filling is executed to display the whole
      duplicated region. Experimental results show that the proposed approach can
      detect duplicated region with high accuracy and robustness to rotation,
      illumination adjustment, blur and JPEG compression while rotation angle is
      estimated precisely for further calculation.

PMID- 22658743
TI  - Evaluation of different sampling media for their potential use as a combined swab
      for the collection of both organic and inorganic explosive residues.
AB  - Commercially available skin cleansing alcohol wipes and conventional swabs were
      investigated for their use as a universal sampling medium for the simultaneous
      collection of both organic and inorganic explosive residues. Six compounds with
      the potential to be encountered in casework [pentaerythritol tetranitrate (PETN),
      2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX),
      triacetone triperoxide (TATP), ammonium nitrate, and sodium chlorate] were
      selected as representative target compounds. Quantities of these target compounds
      were deposited on four different substrates (glass, plastic, aluminium foil and
      laminate). Two chosen alcohol wipes demonstrated better overall performance in
      the recovery of both the organic and inorganic representative compounds from each
      of the test surfaces compared to the results obtained using conventional cotton
      and polyester swabs, pre-moistened with various solvents, and a direct methanol
      wash (used as a control). Results obtained using dry cotton swabs indicated that
      it was not an effective swabbing system for the collection of both organic and
      inorganic explosive residues on common substrates.

PMID- 22658744
TI  - On the autofluorescence of fingermarks.
AB  - The autofluorescence of fingermarks is used for their detection. The components
      responsible for this autofluorescence are largely unknown. Thin layer
      chromatography and fluorescence spectroscopy were used to identify
      autofluorescent components and evaluate their forensic value. Based on our
      results, tryptophan is hypothesized to be a major contributor to the
      autofluorescence when part of peptides or proteins, id est, not in its free form.
      Part of the autofluorescence could be assigned to a kynurenine derivative.
      Pheophorbide A, a metabolite of chlorophyll, is inferred as a red fluorescent
      fingermark component. Chlorophyll is a plant pigment which implies that dietary
      information can potentially be retrieved from fingermarks.

PMID- 22658745
TI  - Cognitive and pharmacological insights from the Ts65Dn mouse model of Down
      syndrome.
AB  - Down syndrome (DS) is a multi-faceted condition resulting in the most common
      genetic form of intellectual disability. Mouse models of DS, especially the
      Ts65Dn model, have been pivotal in furthering our understanding of the genetic,
      molecular and neurobiological mechanisms that underlie learning and memory
      impairments in DS. Cognitive and pharmacological insights from the Ts65Dn mouse
      model have led to remarkable translational progress in the development of
      therapeutic targets and in the emergence of DS clinical trials. Unravelling the
      pathogenic role of trisomic genes on human chromosome 21 and the genotype
      phenotype relationship still remains a pertinent goal for tackling cognitive
      deficits in DS.

PMID- 22658746
TI  - Observational retrospective study on acquired megalourethra after primary
      proximal hypospadias repair and its recurrence after tapering.
AB  - INTRODUCTION: Acquired megalourethra (AMU) after repair of proximal hypospadias
      can be a serious complication. An observational retrospective study of its
      incidence among different types of repair was performed. MATERIALS AND METHODS:
      Clinical charts of patients operated on for proximal hypospadias were reviewed.
      INCLUSION CRITERIA: all primary hypospadias operated in 1991-2004, with the
      meatus positioned in proximal penile, scrotal or perineal position. RESULTS: Of
      770 hypospadias cases treated, 130 (16%) were proximal. Seventy-two patients
      (55%) were treated using preputial flaps: 36 with a tubularized preputial island
      flap (TIF) and 36 an onlay island flap (OIF). Fifty-eight patients (45%)
      underwent staged repairs: Belt-Fuqua (BF) in 18 and Bracka procedure in 40 cases.
      After a mean follow up of 16 years (range 6-19) the overall incidence of
      complications for each technique was: TIF 36%; OIF 33%; BF 25%; two-stage Bracka
      7.5%. The most common complication encountered was neo-urethral fistula. AMU
      occurred in only 5 cases, none with associated distal urethral stenosis, all in
      the TIF and OIF groups, and all successfully treated by reduction re-do
      urethroplasty. CONCLUSION: A very small number of the patients operated using
      preputial island flaps techniques developed AMU. None of the staged repairs
      developed AMU, and this is the preferred choice in proximal hypospadias when the
      urethral plate requires division and/or substitution. All cases of AMU resolved
      after urethral tapering.

PMID- 22658747
TI  - Structural insights into the role of domain flexibility in human DNA ligase IV.
AB  - Knowledge of the architecture of DNA ligase IV (LigIV) and interactions with
      XRCC4 and XLF-Cernunnos is necessary for understanding its role in the ligation
      of double-strand breaks during nonhomologous end joining. Here we report the
      structure of a subdomain of the nucleotidyltrasferase domain of human LigIV and
      provide insights into the residues associated with LIG4 syndrome. We use this
      structural information together with the known structures of the BRCT/XRCC4
      complex and those of LigIV orthologs to interpret small-angle X-ray scattering of
      LigIV in complex with XRCC4 and size exclusion chromatography of LigIV, XRCC4,
      and XLF-Cernunnos. Our results suggest that the flexibility of the catalytic
      region is limited in a manner that affects the formation of the LigIV/XRCC4/XLF
      Cernunnos complex.

PMID- 22658748
TI  - Crystal structures of the outer membrane domain of intimin and invasin from
      enterohemorrhagic E. coli and enteropathogenic Y. pseudotuberculosis.
AB  - Intimins and invasins are virulence factors produced by pathogenic Gram-negative
      bacteria. They contain C-terminal extracellular passenger domains that are
      involved in adhesion to host cells and N-terminal beta domains that are embedded
      in the outer membrane. Here, we identify the domain boundaries of an E. coli
      intimin beta domain and use this information to solve its structure and the beta
      domain structure of a Y. pseudotuberculosis invasin. Both beta domain structures
      crystallized as monomers and reveal that the previous range of residues assigned
      to the beta domain also includes a protease-resistant domain that is part of the
      passenger. Additionally, we identify 146 nonredundant representative members of
      the intimin/invasin family based on the boundaries of the highly conserved
      intimin and invasin beta domains. We then use this set of sequences along with
      our structural data to find and map the evolutionarily constrained residues
      within the beta domain.

PMID- 22658749
TI  - A protein export pathway involving Escherichia coli porins.
AB  - Escherichia coli export the protein YebF into the extracellular medium by a two
      step process. However, as no general outer membrane protein secretion system
      common to all E. coli strains has been reported, the mechanism of export has
      remained unclear. Herein, we identify the outer membrane proteins OmpF, OmpC, and
      OmpX as central to the YebF export mechanism using both genetic and planar lipid
      bilayer experiments. The nuclear magnetic resonance structural ensemble of YebF
      reveals a cystatin-like fold consisting of a structured core and an extended
      dynamic surface in a state of conformational exchange. This surface, conserved
      throughout YebF orthologs of Enterobacteriaceae, may facilitate the porin
      mediated transport of YebF as amino acid substitutions of dynamic residues
      reduced secretion to the extracellular medium. Our results demonstrate that OmpF
      and OmpC not only operate to import ions and protein toxins but may also
      contribute to the export of the YebF protein family.

PMID- 22658751
TI  - The pathophysiological time window study of performing minimally invasive
      procedures for the intracerebral hematoma evacuation in rabbit.
AB  - The objective of this study was to observe the pathophysiological time window of
      performing minimally invasive procedures for the intracerebral hematoma
      evacuation. Thirty-six rabbits were randomly placed in either a normal control
      group (NC group, 6 rabbits), a model control group (MC group, 6 rabbits) or a
      minimally invasive group (MI group, 24 rabbits). A model of intracerebral
      hemorrhage (ICH) was established in the MC and MI groups. In the MI group, the
      intracerebral hematoma was evacuated by stereotactic minimally invasive
      procedures over 6h (6 rabbits), 12h (6 rabbits), 18 h (6 rabbits) and 24h (6
      rabbits), following successful induction of ICH. All of the animals in each group
      were sacrificed 48 h after the successful induction of ICH. Perihematomal brain
      tissues were removed to determine the glutamate level, BBB permeability and brain
      water content (BWC). The perihematomal glutamate level, BBB permeability and the
      BWC in the MI group were significantly decreased compared with those of the MC
      group. Performing minimally invasive procedures for evacuation of ICH in 6h
      showed the most remarkable decrease of the glutamate level, BBB permeability and
      BWC, followed by a significant difference observed at 12h within the MI
      subgroups. Performing minimally invasive procedures in early stages after ICH for
      the hematoma evacuation could decrease the perihematomal glutamate level, BBB
      permeability and BWC significantly. The pathophysiological time window of
      minimally invasive procedures for hematoma evacuation might be 6-12h after
      hemorrhage.

PMID- 22658752
TI  - [An unusual cause of bilateral neuroretinitis: cat scratch disease].

PMID- 22658750
TI  - The T4 phage SF1B helicase Dda is structurally optimized to perform DNA strand
      separation.
AB  - Helicases move on DNA via an ATP binding and hydrolysis mechanism coordinated by
      well-characterized helicase motifs. However, the translocation along single
      stranded DNA (ssDNA) and the strand separation of double-stranded (dsDNA) may be
      loosely or tightly coupled. Dda is a phage T4 SF1B helicase with sequence
      homology to the Pif1 family of helicases that tightly couples translocation to
      strand separation. The crystal structure of the Dda-ssDNA binary complex reveals
      a domain referred to as the "pin" that was previously thought to remain static
      during strand separation. The pin contains a conserved phenylalanine that
      mediates a transient base-stacking interaction that is absolutely required for
      separation of dsDNA. The pin is secured at its tip by protein-protein
      interactions through an extended SH3 domain thereby creating a rigid strut. The
      conserved interface between the pin and the SH3 domain provides the mechanism for
      tight coupling of translocation to strand separation.

PMID- 22658753
TI  - Recommendations for the detection and therapeutic management of cognitive
      impairment in multiple sclerosis.
AB  - The aim of the Multiple Sclerosis Think Tank (Groupe de reflexion sur la sclerose
      en plaques [GRESEP]) is to prescribe recommendations following a systematic
      literature search and using a Rand Corporation and California University
      (RAND/UCLA) appropriateness derived method, in response to practical questions
      that are raised in the management of patients with multiple sclerosis (MS). The
      topics of this working program were chosen because they were not addressed in the
      French recommendations and because of the few data in the literature that enabled
      practices to be based on validated data. Following the theme on useful serum
      testing with suspected multiple sclerosis, the subjects of the present work
      concern the detection and management of cognitive impairment in the beginning
      stages of the disease course. Two clinical questions were asked: which
      complementary exams (besides physical examination and neuropsychological tests)
      would help in the screening of cognitive impairment at the beginning of the
      disease? What care management should the person with MS and cognitive impairment
      be offered (treatments and neurocognitive rehabilitation)? The recommendations
      are the result of a consensus amongst a working group, a rating group and a
      reading group comprised of hospital neurologists involved in the management of
      patients with multiple sclerosis. Each recommendation is presented with the
      degree of consensus that it was accorded.

PMID- 22658754
TI  - Quantitative model of NMR chemical shifts of 23Na+ induced by TmDOTP:
      applications in studies of Na+ transport in human erythrocytes.
AB  - The change in the NMR chemical shift of (23)Na(+) induced by the shift reagent
      TmDOTP was examined under various experimental conditions typical of cells,
      including changed Na(+), K(+), PO(4)(3-), and Ca(2+) concentrations, pH and
      temperature. A mathematical model was developed relating these factors to the
      observed chemical shift change relative to a capillary-sphere reference. This
      enabled cation concentrations to be deduced quantitatively from experimental
      chemical shifts, including those observed during biological time courses with
      cell suspensions containing TmDOTP DOTP, 1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetrakis (methylenephosphonate) [corrected]. The model was applied to a (23)Na
      NMR time course in which monensin, a sodium ionophore, was introduced to human
      erythrocytes, changing the concentration of cations which may bind TmDOTP, and
      also resulting in cell volume changes. Using the model with experimentally
      determined conditions, the chemical shift was predicted and closely followed the
      experimental values over time. In addition to the model, parameter fitting was
      achieved by calculating the likelihood distribution of parameters, and seeking
      the maximum likelihood with a Bayesian type of analysis.

PMID- 22658755
TI  - PcoE--a metal sponge expressed to the periplasm of copper resistance Escherichia
      coli. Implication of its function role in copper resistance.
AB  - Expression of the periplasmic protein PcoE of Escherichia coli is induced
      strongly by cupric salts under the control of the chromosomal copper tolerance
      system cusRS. Its isolation and study were complicated by de-amidation of Asn 54
      and 103 at alkaline pH. Its apo form is essentially unstructured in solution and
      can be likened to a large unstructured multidentate ligand carrying multiple
      metal binding sites (15 Met; 10 His; 13 Asp, Glu; 10 Asn; 6 Lys). As expected, it
      binds multiple soft metal ions Cu(+) and Ag(+) non-cooperatively with the highest
      affinity for Cu(I) in the picomolar range (K(D)~10(-12) M). Binding of multiple
      soft ions induced dimerization and formation of some alpha-helical structure.
      PcoE also binds the harder metal ions Cu(2+) or Zn(2+) but with lower affinities
      and in smaller numbers. Cu(II) bound in PcoE is reduced readily to more tightly
      bound Cu(I). Overall, these properties mean that it is difficult to characterize
      individual species of defined metal content. Similar properties and difficulties
      have been reported for the homologous silver-binding protein SilE from
      Salmonella. However, the properties are consistent with a role for PcoE as a
      'metal sponge' acting as a first line of defence against metal toxicity (under
      the control of the copper tolerance system cusRS) until the copper resistance
      operon pcoABCD is expressed.

PMID- 22658756
TI  - Inner- and outer-sphere metal coordination in blue copper proteins.
AB  - Blue copper proteins (BCPs) comprise classic cases of Nature's profound control
      over the electronic structures and chemical reactivity of transition metal ions.
      Early studies of BCPs focused on their inner coordination spheres, that is,
      residues that directly coordinate Cu. Equally important are the electronic and
      geometric perturbations to these ligands provided by the outer coordination
      sphere. In this tribute to Hans Freeman, we review investigations that have
      advanced the understanding of how inner-sphere and outer-sphere coordination
      affects biological Cu properties.

PMID- 22658758
TI  - Serum testosterone and dihydrotestosterone and prostate cancer risk in the
      placebo arm of the Reduction by Dutasteride of Prostate Cancer Events trial.
AB  - BACKGROUND: Findings of studies on the association between androgens and prostate
      cancer (PCa) are mixed. Androgens may affect prostate-specific antigen (PSA)
      levels, thereby influencing biopsy recommendations. Also, androgens may stimulate
      prostate growth at very low levels with no additional effects at higher levels
      (saturation model). OBJECTIVE: To test whether androgens were associated with PCa
      risk in the placebo arm of a prospective study in which biopsies were performed
      regardless of PSA level. DESIGN, SETTING, AND PARTICIPANTS: Of 8122 men in the
      Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, 4073 men
      (50.1%) received placebo. Key entry criteria were PSA 2.5-10 ng/ml and one prior
      negative biopsy. INTERVENTION: Per-protocol biopsies at 2 and 4 yr; for-cause
      biopsies at physician discretion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Multivariable logistic regression was used to test the association between
      baseline log-transformed testosterone and dihydrotestosterone (DHT) levels and
      the risk of detecting either PCa or low-grade PCa (Gleason score <6) compared
      with high-grade PCa (Gleason score >7). In secondary analysis, we stratified the
      analysis by low baseline androgen levels (testosterone <10 nmol/l; DHT <0.76
      nmol/l) compared with normal baseline androgen levels. RESULTS AND LIMITATIONS:
      Of 4073 men, 3255 (79.9%) had at least one biopsy after randomization and were
      analyzed. Androgen levels tested continuously or by quintiles were generally
      unrelated to PCa detection or grade. PCa detection was similar among men with low
      compared with normal baseline testosterone levels (25.5% and 25.1%; p=0.831). In
      secondary analysis, higher testosterone levels at baseline were associated with
      higher PCa detection (odds ratio: 1.23; 95% confidence interval, 1.06-1.43;
      p=0.006) only if men had low baseline testosterone (<10nmol/l). For men with
      normal baseline testosterone (>=10 nmol/l), higher testosterone levels at
      baseline were unrelated to PCa risk (p=0.33). No association was found for DHT
      and PCa (all p>0.85). CONCLUSIONS: Baseline serum testosterone and DHT levels
      were unrelated to PCa detection or grade. Our findings of the lowest testosterone
      levels being associated with the lowest PCa risk with no further changes with
      higher testosterone support a saturation model but must be confirmed in future
      studies using an a priori defined hypothesis. CLINICALTRIALS.GOV IDENTIFIER:
      NCT00056407.

PMID- 22658759
TI  - Robot-assisted laparoscopic partial nephrectomy: step-by-step contemporary
      technique and surgical outcomes at a single high-volume institution.
AB  - BACKGROUND: Robotic technology is being increasingly adopted in urologic surgery.
      OBJECTIVE: To describe a contemporary surgical technique and report cumulative
      surgical outcomes of robot-assisted laparoscopic partial nephrectomy (RALPN) at
      our tertiary care institution. DESIGN, SETTING, AND PARTICIPANTS: Medical charts
      of consecutive patients who underwent RALPN between June 2006 and November 2011
      were reviewed from a prospectively maintained, institutional review board
      approved database. SURGICAL PROCEDURE: The main steps of our current surgical
      technique are described in this video tutorial: patient positioning and trocar
      placement; bowel mobilization; hilar dissection; tumor identification and
      demarcation; clamping of the hilum; tumor excision; renorraphy; hilar unclamping;
      and tumor retrieval. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients'
      characteristics and main surgical outcomes were analyzed. RESULTS AND
      LIMITATIONS: A total of 400 patients (mean age: 58.5 yr, mean body mass index:
      30.7 kg/m(2)) were included in this analysis. Mean renal tumor size was 3.17 cm
      (standard deviation [SD]: 1.64) and mean RENAL score was 7.2 (SD: 2). Six
      patients (1.5%) presented with a solitary kidney. Mean total operative time was
      190.3 min (SD: 57), and mean warm ischemia time was 19.2 min (SD: 10.72). In 36
      cases (9%), an unclamped hilum technique was used. After a mean follow-up of 12.4
      mo (SD: 12.2), there was a decline of -9.2 ml/min per 1.73 m(2) (SD: 26.56) in
      estimated glomerular filtration rate. Most renal masses were malignant (74.5%),
      and the overall mean tumor size was 3.05 cm (SD: 1.66). Renal cell carcinoma with
      a clear cell histology represented the most frequent malignant diagnosis (64.4%
      of cases). A positive margin was observed in nine cases (2.25%). A total of 11
      intraoperative complications (2.7%) occurred, and a conversion to open or
      laparoscopic PN was required in six cases (1.5%). A postoperative complication
      occurred in 61 cases (15.3%), the majority of them being low grade. CONCLUSIONS:
      The standardization of each surgical step has allowed for optimization of RALPN
      and ultimately improved its outcomes and expanded its indications.

PMID- 22658761
TI  - EAU guidelines on penile curvature.
AB  - CONTEXT: Penile curvature can be congenital or acquired. Acquired curvature is
      secondary due to La Peyronie (Peyronie's) disease. OBJECTIVE: To provide clinical
      guidelines on the diagnosis and treatment of penile curvature. EVIDENCE
      ACQUISITION: A systematic literature search on the epidemiology, diagnosis, and
      treatment of penile curvature was performed. Articles with the highest evidence
      available were selected and formed the basis for assigning levels of evidence and
      grades of recommendations. EVIDENCE SYNTHESIS: The pathogenesis of congenital
      penile curvature is unknown. Peyronie's disease is a poorly understood connective
      tissue disorder most commonly attributed to repetitive microvascular injury or
      trauma during intercourse. Diagnosis is based on medical and sexual histories,
      which are sufficient to establish the diagnosis. Physical examination includes
      assessment of palpable nodules and penile length. Curvature is best documented by
      a self-photograph or pharmacologically induced erection. The only treatment
      option for congenital penile curvature is surgery based on plication techniques.
      Conservative treatment for Peyronie's disease is associated with poor outcomes.
      Pharmacotherapy includes oral potassium para-aminobenzoate, intralesional
      treatment with verapamil, clostridial collagenase or interferon, topical
      verapamil gel, and iontophoresis with verapamil and dexamethasone. They can be
      efficacious in some patients, but none of these options carry a grade A
      recommendation. Steroids, vitamin E, and tamoxifen cannot be recommended.
      Extracorporeal shock wave treatment and penile traction devices may only be used
      to treat penile pain and reduce penile deformity, respectively. Surgery is
      indicated when Peyronie's disease is stable for at least 3 mo. Tunical shortening
      procedures, especially plication techniques, are the first treatment options.
      Tunical lengthening procedures are preferred in more severe curvatures or in
      complex deformities. Penile prosthesis implantation is recommended in patients
      with erectile dysfunction not responding to pharmacotherapy. CONCLUSIONS: These
      European Association of Urology (EAU) guidelines summarise the present
      information on penile curvature. The extended version of the guidelines is
      available on the EAU Web site (www.uroweb.org/guidelines/).

PMID- 22658763
TI  - Immunosenescence and HIV.
AB  - PURPOSE OF REVIEW: The present review discusses the interplay between HIV
      infection and other environmental factors (e.g. co-infection with CMV) in the
      acceleration of the aging process of the immune system, leading to
      'immunosenescence.' RECENT FINDINGS: Basic studies in cell biology demonstrate
      that replicative senescence is a common pathway of many cell lineages, including
      those of the immune system, characterized by activation of a unique pro
      inflammatory secretory program. In the setting of HIV disease, this process is
      accelerated, resulting in an immunosuppressed state that diminishes the ability
      of the immune system to contain virus while at the same time facilitating viral
      replication and spread. Clinically, these changes result in a lower capacity to
      respond to new infections as well as an increased frequency of age-associated end
      organ disease (e.g. cardiovascular complications, cancer, and neurologic
      disease). SUMMARY: Accelerated immunosenescence in the setting of HIV disease is
      associated with increased morbidity and mortality, prompting the need for more
      investigation into its causes, diagnosis, and treatment.

PMID- 22658762
TI  - Co-infection subverts mucosal immunity in the upper respiratory tract.
AB  - Polymicrobial interactions on mucosal surfaces can influence inflammation,
      immunity, and disease outcome. Here, we review how host responses to colonization
      in the upper respiratory tract with the bacterial pathogen Streptococcus
      pneumoniae can be altered by co-infection. Recent advances provide a mechanistic
      understanding of how mucosal immunity can be subverted at distinct immunological
      time-points during pneumococcal colonization by other pathogens such as
      Haemophilus influenzae, influenza type A and Staphylococcus aureus. These
      examples use animal models of co-infection to highlight how otherwise effective
      host responses can be rendered ineffective by co-infection, and vice versa. The
      complex microbial ecology of mucosal sites must be considered to fully understand
      how immune responses in a natural setting influence the outcome of host-pathogen
      interactions.

PMID- 22658764
TI  - Dosimetric comparison between two MLC systems commonly used for stereotactic
      radiosurgery and radiotherapy: a Monte Carlo and experimental study.
AB  - In this work dosimetric parameters of two multi-leaf collimator (MLC) systems,
      namely the beam modulator (BM), which is the MLC commercial name for Elekta
      "Synergy S" linear accelerator and Radionics micro-MLC (MMLC), are compared using
      measurements and Monte Carlo simulations. Dosimetric parameters, such as
      percentage depth doses (PDDs), in-plane and cross-plane dose profiles, and
      penumbras for different depths and field sizes of the 6 MV photon beams were
      measured using ionization chamber and a water tank. The collimator leakages were
      measured using radiographic films. MMLC and BM were modeled using the EGSnrc
      based BEAMnrc Monte Carlo code and above dosimetric parameters were calculated.
      The energy fluence spectra for the two MLCs were also determined using the
      BEAMnrc and BEAMDP. Dosimetric parameters of the two MLCs were similar, except
      for penumbras. Leaf-side and leaf-end 80-20% dose penumbras at 10 cm depth for a
      10*10 cm(2) field size were 4.8 and 5.1mm for MMLC and 5.3 mm and 6.3 mm for BM,
      respectively. Both Radionics MMLC and Elekta BM can be used effectively based on
      their dosimetric characteristics for stereotactic radiosurgery and radiotherapy,
      although the former showed slightly sharper dose penumbra especially in the leaf
      end direction.

PMID- 22658765
TI  - Safety of low-molecular-weight heparin during pregnancy: a retrospective
      controlled cohort study.
AB  - OBJECTIVE: To study the safety of low-molecular-weight heparin (LMWH) treatment
      during pregnancy for the mother and the foetus. STUDY DESIGN: Retrospective
      controlled cohort study. Six hundred and forty-eight pregnancies exposed to LMWH
      were compared with 626 unexposed pregnancies. Principal characteristics,
      indications for LMWH use, and maternal and foetal complications were reported for
      each pregnancy. Data were obtained from patients' electronic hospital records and
      analysed using Statistical Package for the Social Sciences Version 17.0. RESULTS:
      The incidence rates of various pregnancy complications did not differ between the
      groups (LMWH group vs control group): 1.56% vs 1.1% for thrombocytopenia, 8.7% vs
      6.5% for preterm delivery, 0.7% vs 0.3% for stillbirth, 1.4% vs 1.0% for severe
      pre-eclampsia, 2.7% vs 2.2% for foetal growth restriction, and 10.7% vs 7.8% for
      antenatal bleeding. One serious antenatal maternal haemorrhage occurred in the
      LMWH group (0.15%), but this was unrelated to LMWH use. The caesarean section
      rate and the amount of bleeding during delivery were similar in the two groups
      (21% vs 19% and 500 vs 450 ml, respectively). The risk of major blood loss during
      labour (>1000 ml) was no higher in the LMWH group compared with the control
      group. The incidence of allergic skin reactions was 0.3% in the LMWH group. No
      heparin-induced thrombocytopenia or symptomatic osteoporotic fractures were
      observed. Recurrent venous thromboembolic events occurred in 2.5% of patients in
      the LMWH group. CONCLUSION: This study indicates that the use of LMWH is safe
      during pregnancy.

PMID- 22658766
TI  - Leptin drives fat distribution during diet-induced obesity in mice.
AB  - OBJECTIVE: Desensitization of leptin receptors is a process that specifically
      occurs in some tissues. We have hypothesized that during the development of
      obesity tissue lipids would increase gradually in particular organs depending on
      leptin responsiveness. Our aim was to establish a relationship between leptin
      resistance and lipid deposition by using a model of diet-induced obesity (DIO)
      and we have characterized, in mice undergoing a dietary treatment with a high-fat
      (HF) diet, the evolution of lipid content and leptin responsiveness in white
      adipose tissue and liver. METHODS: Four-week-old male C57BL/6J mice were divided
      into two groups and assigned either to a low-fat or to a high-fat diet. Dietary
      treatment lasted 8, 20 or 32 weeks. The last day animals received 1mg/kg leptin
      and then tissues were weighed and processed for Western-blotting and lipid
      determination. RESULTS: We observed an initial increase of the relative weight of
      adipose pads that was blunted after 32-week HF. In contrast, liver size exhibited
      an initial decrease followed by a progressive increase, which was coincident with
      the increase of hepatic triglycerides and with the impairment of leptin receptor
      signalling. CONCLUSION: Our data show that leptin resistance within white adipose
      tissue does not deal with an increase of the size of adipose pads and suggest
      that consequences of leptin resistance, in terms of fat accumulation, are tissue
      dependent.

PMID- 22658767
TI  - Plasmodium yoelii blood-stage antigens newly identified by immunoaffinity using
      purified IgG antibodies from malaria-resistant mice.
AB  - As the search for an effective human malaria vaccine continues, understanding
      immune responses to Plasmodium in rodent models is perhaps the key to unlocking
      new vaccine strategies. The recruitment of parasite-specific antibodies is an
      important component of natural immunity against infection in blood-stage malaria.
      Here, we describe the use of sera from naturally surviving ICR mice after
      infection with lethal doses of Plasmodium yoelii yoelii 17XL to identify highly
      immunogenic blood-stage antigens. Immobilized protein A/G was used for the
      affinity-chromatography purification of the IgGs present in pooled sera from
      surviving mice. These protective IgGs, covalently immobilized on agarose columns,
      were then used to isolate reactive antigens from whole P. yoelii yoelii 17XL
      protein extracts obtained from the blood-stage malaria infection. Through
      proteomics analysis of the recovered parasite antigens, we were able to identify
      two endoplasmic reticulum lumen proteins: protein disulfide isomerase and a
      member of the heat shock protein 70 family. Also identified were the digestive
      protease plasmepsin and the 39 kDa-subunit of eukaryotic translation initiation
      factor 3, a ribosome associated protein. Of these four proteins, three have not
      been previously identified as antigenic during blood-stage malaria infection.
      This procedure of isolating and identifying parasite antigens using serum IgGs
      from malaria-protected individuals could be a novel strategy for the development
      of multi-antigen-based vaccine therapies.

PMID- 22658768
TI  - Black South African farm workers' beliefs about HIV.
AB  - Black South African farm workers' context of an isolated lifestyle and lack of
      education and resources might lead to unique beliefs that influence their
      understanding and behavior regarding HIV infection. An exploration and
      description of these beliefs can inform suggestions for a belief-sensitive
      approach for HIV-prevention programs. A participative rural appraisal research
      method was implemented, following a qualitative, explorative, and descriptive
      approach. A culturally sensitive mode of interviewing, namely lekgotla, was used
      as a strategy to collect data. The results indicated that Black South African
      farm workers have specific beliefs about HIV. Most of the beliefs protect them
      from being infected, but some marginal beliefs can put them at risk of being
      infected. Clinical considerations, which health care professionals can
      incorporate in HIV-prevention programs, were formulated based on the results,
      relevant literature, and conclusions.

PMID- 22658769
TI  - Exploring research fatigue in HIV-infected youth.

PMID- 22658770
TI  - Low-temperature fabrication of TiO(2) electrodes for flexible dye-sensitized
      solar cells using an electrospray process.
AB  - Hierarchically structured TiO2 (HS-TiO2) was prepared on a flexible ITO-PEN
      (polyethylene naphthalate) substrate via electrospray deposition using a
      commercially available TiO2 nanocrystalline powder in order to fabricate flexible
      DSSCs under low-temperature (<150  degrees C) conditions. The cell efficiency
      increased when using flexible ITO-PEN substrates post-treated by either a
      mechanical compression treatment or a chemical sintering treatment using titanium
      n-tetrabutoxide (TTB). The mechanical compression treatment reduced the surface
      area and porosity of the HS-TiO2; however, this treatment improved the
      interparticle connectivity and physical adhesion between the HS-TiO2 and ITO-PEN
      substrate, which increased the photocurrent density of the as-pressed HS-TiO2
      cells. The electron diffusion coefficients of the as-pressed HS-TiO2 improved
      upon compression treatment, whereas the recombination lifetimes remained
      unchanged. An additional chemical sintering post-treatment involving TTB was
      tested for its effects on DSSC efficiency. The freshly coated TiO2 submitted to
      TTB hydrolysis in water at 100  degrees C yielded an anatase phase. TTB treatment
      of the HS-TiO2 cell after compression treatment yielded faster electron
      diffusion, providing an efficiency of 5.57% under 100 mW cm(-2), AM 1.5 global
      illumination. 

PMID- 22658771
TI  - European Network of Forensic Science Institutes (ENFSI): Evaluation of new
      commercial STR multiplexes that include the European Standard Set (ESS) of
      markers.
AB  - To support and to underpin the European initiative to increase the European set
      of standard markers (ESS), by the addition of five new loci, a collaborative
      project was organised by the European Network of Forensic Science Institutes
      (ENFSI) DNA working group in order to assess the new multiplex kits available. We
      have prepared allele frequency databases from 26 EU populations. Concordance
      studies were carried out to verify that genotyping results were consistent
      between kits. Population genetics studies were conducted and it was estimated
      that F(ST)<0.001. The results showed that the kits were comparable to each other
      in terms of performance and major discrepancy issues were highlighted. We provide
      details of allele frequencies for each of the populations analysed per
      laboratory.

PMID- 22658772
TI  - Commentary on 'use of colour duplex ultrasound as a first line surveillance tool
      following Evar is associated with a reduction in cost without compromising
      accuracy'.

PMID- 22658773
TI  - Role of thrombophilia in premature peripheral arterial obstructive disease -
      experience of a vascular centre in China.
AB  - OBJECTIVE: To evaluate aetiology profile and role of thrombophilia in patients
      with premature peripheral arterial obstructive disease (PAOD) in China. METHODS:
      Between January 2000 and January 2010, among 368 patients presenting with PAOD,
      but not Buerger's disease, at an age of less than 45 years, 150 patients have
      been screened for thrombophilia and the data analysed retrospectively.
      Aetiologies of thrombophilia which involved in premature PAOD were assessed and
      surgical outcomes were stratified for presence of thrombophilia. RESULTS: In 57
      of 150 patients (38%), laboratory assay results suggested thrombophilia, and the
      rest of them presented with other aetiology (62%). A total of 108 patients,
      including 38 patients with thrombophilia (35%), needed some type of
      revascularisation. At 30 days, recurrent thrombosis (29% vs. 9%; p = 0.005) and
      major amputations (11% vs. 1%; p = 0.032) were more common in patients with
      thrombophilia. At 1 year, primary patency (56% vs. 75%, p = 0.043), secondary
      patency (68% vs. 92%, p = 0.036) and limb salvage (74% vs. 96%, p = 0.038) were
      significantly lower in patients with thrombophilia. CONCLUSION: Thrombophilia is
      frequently diagnosed among premature PAOD in China and adversely affects outcome
      after revascularisation. Clinicians should be aware of its high prevalence and
      aim at screening and sustained thrombophilia treatment.

PMID- 22658774
TI  - Epidemiology and outcome of vascular trauma at a British Major Trauma Centre.
AB  - OBJECTIVES: In the United Kingdom, the epidemiology, management strategies and
      outcomes from vascular trauma are unknown. The aim of this study was to describe
      the vascular trauma experience of a British Trauma Centre. METHODS: A
      retrospective observational study of all patients admitted to hospital with
      traumatic vascular injury between 2005 and 2010. RESULTS: Vascular injuries were
      present in 256 patients (4.4%) of the 5823 total trauma admissions. Penetrating
      trauma caused 135 (53%) vascular injuries whilst the remainder resulted from
      blunt trauma. Compared to penetrating vascular trauma, patients with blunt trauma
      were more severely injured (median ISS 29 [18-38] vs. ISS 11 [9-17], p < 0.0001),
      had greater mortality (26% vs. 10%; OR 3.0, 95% CI 1.5-5.9; p < 0.01) and higher
      limb amputation rates (12% vs. 0%; p < 0.0001). Blunt vascular trauma patients
      were also twice as likely to require a massive blood transfusion (48% vs. 25%; p
      = 0.0002) and had a five-fold longer hospital length of stay (median 35 days (15
      58) vs. 7 (4-13), p<0.0001) and critical care stay (median 5 days (0-11) vs. 0 (0
      2), p < 0.0001) compared to patients with penetrating trauma. Multivariate
      regression analysis showed that age, ISS, shock and zone of injury were
      independent predictors of death following vascular trauma. CONCLUSION: Traumatic
      vascular injury accounts for 4% of admissions to a British Trauma Centre. These
      patients are severely injured with high mortality and morbidity, and place a
      significant demand on hospital resources. Integration of vascular services with
      regional trauma systems will be an essential part of current efforts to improve
      trauma care in the UK.

PMID- 22658775
TI  - A ten year review of civilian iliac vessel injuries from a single trauma centre.
AB  - OBJECTIVE: To report the surgical management and outcome of iliac vessel (IV)
      injuries in a civilian trauma centre with a high incidence of penetrating trauma.
      DESIGN, PATIENTS AND METHODS: A retrospective record review of patients with IV
      injuries treated between January 2000 and December 2009. RESULTS: Sixty nine
      patients, 59 with gunshot wounds, sustained 108 iliac vessel injuries. Mean
      revised trauma and injury severity scores was 7.06 and 28.4, respectively. Twenty
      nine patients required damage control laparotomy. Common or external iliac
      arteries were repaired by primary repair (10), temporary shunt with delayed graft
      (6), interposition graft (5) or ligation if limb non-viable (3). Forty-seven
      patients had injuries to the common or external iliac vein, 42 were ligated.
      Mortality was 25% and 6 survivors required amputation. CONCLUSIONS: In a stable
      patient a primary arterial repair is preferred but a temporary shunt can be a
      life and limb saving option in the unstable patient. Ligating the common or
      external iliac veins is associated with a low incidence of prolonged leg
      swelling.

PMID- 22658776
TI  - A clinical experience of the supraclavicular flap used to reconstruct head and
      neck defects in late-stage cancer patients.
AB  - The supraclavicular island flap has been widely used in head and neck
      reconstruction, providing an alternative to the traditional techniques like
      regional or free flaps, mainly because of its thin skin island tissue and
      reliable vascularity. Head and neck patients who require large reconstructions
      usually present poor clinical and healing conditions. An early experience using
      this flap for late-stage head and neck tumour treatment is reported. Forty-seven
      supraclavicular artery flaps were used to treat head and neck oncologic defects
      after cutaneous, intraoral and pharyngeal tumour resections. Dissection time,
      complications, donor and reconstructed area outcomes were assessed. The mean time
      for harvesting the flaps was 50 min by the senior author. All donor sites were
      closed primarily. Three cases of laryngopharyngectomy reconstruction developed a
      small controlled (salivary) leak that was resolved with conservative measures.
      Small or no strictures were detected on radiologic swallowing examinations and
      all patients regained normal swallowing function. Five patients developed donor
      site dehiscence. These wounds were treated with regular dressing until healing
      was complete. There were four distal flap necroses in this series. These necroses
      were debrided and closed primarily. The supraclavicular flap is pliable for head
      and neck oncologic reconstruction in late-stage patients. High-risk patients and
      modified radical neck dissection are not contraindications for its use. The
      absence of the need to isolate the pedicle offers quick and reliable harvesting.
      The arc of rotation on the base of the neck provides adequate length for
      pharyngeal, oral lining and to reconstruct the middle and superior third of the
      face.

PMID- 22658777
TI  - Patients' perceptions of a health information exchange: a pilot program in South
      Korea.
AB  - OBJECTIVES: We examined patients' perceived need for a Health Information
      Exchange (HIE), their preferences regarding information exchange operations,
      endorsement of the technology, and expected and perceived benefits and concerns
      about the technology. Through an HIE pilot program in South Korea, we also
      explored the influence of demographic characteristics and HIE experience on
      patients' perceptions. MATERIAL AND METHODS: We collected data from patient
      surveys administered through a structured questionnaire pre- and post
      implementation of an HIE in South Korea. The study database contained 730 records
      collected by survey before program rollout, 306 records from patients who had
      experienced the HIE, and 180 records in the comparison group A who experienced an
      offline-based exchange through procedures such as bringing copies of medical
      records and imaging results from the clinic to the hospital and 208 records in
      the comparison group B who brought only a referral letter. We computed
      descriptive statistics based on survey responses and performed multiple analyses
      of variance and chi-square tests to examine whether patient characteristics and
      HIE experience influenced responses. RESULTS: Despite their concerns about
      information safety and security, respondents in all 4 (1 pre-implementation and 3
      post-implementation) surveyed groups indicated an acceptance of and willingness
      to endorse HIE technology. Eighty percent of respondents with the HIE experience
      chose HIE as their preferred operation of information exchange whereas the figure
      was 55% and 59% in the comparison groups A and B, respectively. The proportion of
      respondents who indicated improved quality as the reason for their willingness to
      recommend or to participate was higher than the proportion who cited reduced
      healthcare bills in all 3 groups - 8% in the HIE group and 13% and 23% in the
      comparison groups A and B, respectively, cited improved quality as the reason and
      .4% in the HIE group and 4% and 8% in the comparison groups A and B,
      respectively, cited reduced healthcare bills as the reason. CONCLUSIONS: The
      public sentiment is favorable for HIE technology in South Korea, but study
      findings indicate a gap among perceptions of different patient groups. Education
      and other efforts to give the public accurate information on benefits and adverse
      effects of the technology are needed. Also, additional objective studies with
      empirical data should be conducted to obtain quantitative evidence of benefits
      and adverse effects of the technology.

PMID- 22658778
TI  - An exploratory study of ageing women's perception on access to health informatics
      via a mobile phone-based intervention.
AB  - OBJECTIVE: This is an exploratory study examining the perceived attitudes and
      readiness of women aged 50 years or older on adopting a mobile phone-based
      intervention named as Infohealth in Singapore. METHOD: Infohealth is designed as
      a health informatics to tailor personalized healthcare advice for the well-being
      for women - very little is known about the acceptability level of self-care
      technology, especially the older among the female population. To explore
      participants' perceptions and acceptance, a telephone survey was developed from
      concepts identified from various user acceptance theories and models. Correlation
      was used to identify significant dependent variables while partial least square
      and boot-strapping procedures were used to estimate the significance of the path
      coefficients. RESULTS: Analysis supports the validity and reliability of the 27
      item research model consisting of 8 constructs. 700 women aged 50years and older
      responded to the survey. Findings show the extent of ageing women's existing
      dependency on others for help, regard for close ones whom they care for, opinion
      from family and friends, and guarding the health of people who are important for
      them do not directly affect the intention of using Infohealth, but are rather
      mediated by perceived usefulness. This study validated some ageing-specific and
      female-posited variables to suggest as main constructs in future innovation
      adoption studies about older women. Technological anxiety and perceived physical
      condition both have no direct relationship with perceived ease of use and
      usefulness, lifestyle and intention to use. CONCLUSION: Findings reinforced the
      significant roles of perceived usefulness and perceived ease of use,
      compatibility, and subjective norm in predicting the adoption intention of
      Infohealth among ageing women. More extensive statistical analysis is needed to
      discover more interesting findings while qualitative analysis can help to detect
      humanistic design opportunities.

PMID- 22658780
TI  - Physiological response and photoacclimation capacity of Caulerpa prolifera
      (Forsskal) J.V. Lamouroux and Cymodocea nodosa (Ucria) Ascherson meadows in the
      Mar Menor lagoon (SE Spain).
AB  - The macroalga Caulerpa prolifera colonized the Mar Menor coastal lagoon after the
      enlargement of the main inlet in 1972, coexisting now with the previous Cymodocea
      nodosa meadows. The physiological response and the photoacclimation capacity of
      both species were studied. For this purpose in vivo chlorophyll a fluorescence,
      photoprotective mechanisms and oxidative stress were measured in both species in
      summer 2010 and exposure-recovery experiments were conducted to determine the
      acclimation capacity of both species. The results suggest that C. prolifera
      behaves as a shade-adapted species with a low photoprotective capacity, light
      being one of the main factors governing its distribution in the lagoon. The high
      photosynthetic capacity and lack of photoinhibition found in C. nodosa suggest
      that this species is highly photoprotected. It also possesses a high
      concentration of lutein and a high de-epoxidation degree, related to a much
      higher NPQ(max) value.

PMID- 22658779
TI  - Recent developments in single-molecule DNA mechanics.
AB  - Over the past two decades, measurements on individual stretched and twisted DNA
      molecules have helped define the basic elastic properties of the double helix and
      enabled real-time functional assays of DNA-associated molecular machines.
      Recently, new magnetic tweezers approaches for simultaneously measuring freely
      fluctuating twist and extension have begun to shed light on the structural
      dynamics of large nucleoprotein complexes. Related technical advances have
      facilitated direct measurements of DNA torque, contributing to a better
      understanding of abrupt structural transitions in mechanically stressed DNA. The
      new measurements have also been exploited in studies that hint at a developing
      synergistic relationship between single-molecule manipulation and structural DNA
      nanotechnology.

PMID- 22658781
TI  - Malignant myoepithelioma of the soft palate.
AB  - Malignant myoepitheliomas (MM) (myoepithelial carcinomas) are rare tumors
      representing <1% of salivary gland tumors. They are characterized as being
      locally aggressive. Rarely do they present distant metastases; however, when they
      do metastasize the sites most affected are the lungs, liver, pleura, peritoneum
      and skin. They may originate de novo in a pleomorphic adenoma or a benign
      myoepithelioma. We report the case of a patient with a submucosal lesion of the
      soft palate measuring ~4cm*3cm. The patient underwent transoral resection with a
      microscope and CO2 laser. Histopathological report was MM originating in a
      pleomorphic adenoma. Management of this neoplasm is controversial. Myoepithelial
      carcinoma is a rare neoplasm whose diagnosis includes immunohistochemical (IHC)
      studies. Surgery is the cornerstone of treatment. Management with laser surgery
      may preserve the function of the soft palate without deterioration of the quality
      of life in these patients.

PMID- 22658782
TI  - Monosomy 3 by FISH in uveal melanoma: variability in techniques and results.
AB  - Tumor monosomy 3 confers a poor prognosis in patients with uveal melanoma. We
      critically review the techniques used for fluorescence in situ hybridization
      (FISH) detection of monosomy 3 in order to assess variability in practice
      patterns and to explain differences in results. Significant variability that has
      likely affected reported results was found in tissue sampling methods, selection
      of FISH probes, number of cells counted, and the cut-off point used to determine
      monosomy 3 status. Clinical parameters and specific techniques employed to report
      FISH results should be specified so as to allow meta-analysis of published
      studies. FISH-based detection of monosomy 3 in uveal melanoma has not been
      performed in a standardized manner, which limits conclusions regarding its
      clinical utility. FISH is a widely available, versatile technology, and when
      performed optimally has the potential to be a valuable tool for determining the
      prognosis of uveal melanoma.

PMID- 22658784
TI  - Urinary incontinence due to the presence of necrotic adult Schistosoma
      haematobium parasite in the bladder following travel to Egypt.
AB  - A case of seronegative urinary Schistosomiasis is reported in a 68-year-old
      Caucasian male presenting with urgency of micturition and incontinence several
      months after bathing in a chlorinated pool of a first class hotel in Egypt. The
      symptoms were initiated by a necrotic adult Schistosoma haematobium parasite
      found in the urinary bladder following a cystoscopic examination. The purpose of
      this report is to describe this probable and uncommon source of Schistosomiasis,
      to demonstrate that Schistosoma parasites can also be found in the urinary
      bladder and to emphasize the importance of travel history.

PMID- 22658783
TI  - Evaluation of inflammatory and angiogenic factors in patients with non-alcoholic
      fatty liver disease.
AB  - The liver is a major target of injury in obese patients. Non-alcoholic fatty
      liver disease (NAFLD) is present in 60-90% of obese Americans and can range from
      simple steatosis to the more severe non-alcoholic steatohepatitis (NASH). The
      onset of a chronic inflammatory reaction marks the progression from simple
      steatosis to NASH and the expansion of adipose tissue is strongly associated with
      angiogenesis. Therefore, we determined the serum concentration of inflammatory
      [tumor necrosis factor alpha (TNFalpha) and interleukin 6 (IL6)] and angiogenic
      [vascular endothelial growth factor A (VEGF)] cytokines and soluble VEGF
      receptors 1 and 2 (sVEGFR1, sVEGFR2) in the serum of an obese population with
      simple steatosis and NASH compared to healthy controls. Moreover, we determined
      the TNFalpha, IL6, VEGF, VEGFR1 and VEGFR2 gene expression in the liver of these
      simple steatosis and NASH patients. The population consisted of 30 obese
      patients, which were diagnosed with simple steatosis and 32 patients with NASH
      and compared to 30 age-and-sex matched healthy controls. Mean serum TNFalpha
      levels were elevated in the serum of simple steatosis and NASH patients compared
      to healthy controls, reaching significance in NASH patients. IL6 was
      significantly increased in simple steatosis and NASH patients compared to the
      healthy controls. VEGF levels were significantly elevated in patients with simple
      steatosis and borderline significantly elevated in NASH patients compared to the
      serum levels of healthy control subjects. The concentration of sVEGFR1 was
      significantly increased in serum of simple steatosis and NASH patients compared
      to controls. sVEGFR2 concentration was not significantly different in the three
      groups. TNFalpha mRNA expression was higher in NASH patients compared to simple
      steatosis patients. Hepatic gene expression of VEGF, VEGFR1 and VEGFR2 were
      slightly decreased in NASH patients compared to simple steatosis patients. These
      data indicate the involvement of inflammatory (TNFalpha and IL6), angiogenic
      (VEGF) cytokines and sVEGFR1 in the pathophysiology of NAFLD.

PMID- 22658785
TI  - Randomized crossover study of neurally adjusted ventilatory assist in preterm
      infants.
AB  - OBJECTIVE: To determine whether neurally adjusted ventilatory assist (NAVA), a
      new method of mechanical ventilation that delivers pressure assistance that is
      proportional to the electrical activity of the diaphragm (EAdi), could lower the
      inspiratory pressure and respiratory muscle load in preterm infants supported
      with ventilators. STUDY DESIGN: Twenty-six mechanically ventilated preterm
      infants were randomized to crossover ventilation with NAVA and synchronized
      intermittent mandatory ventilation (SIMV) with pressure support (PS) for 4 hours
      each in a randomized order. A 1-hour interval for washout was provided between
      the 2 modes of ventilation. The ventilator settings were adjusted to maintain
      similar levels of end-tidal partial pressure of CO(2). The ventilator parameters,
      vital signs, and gas exchange effects under the 2 ventilatory modes were
      compared. RESULTS: Nineteen infants completed the 9-hour crossover comparison
      protocol. Peak inspiratory pressure (PIP), work of breathing, and peak EAdi with
      NAVA were lower than those in SIMV with PS. Calculated tidal volume to peak EAdi
      ratio and PIP to peak EAdi ratio were higher with NAVA. There were no significant
      differences in mean airway pressure, inspiratory oxygen fraction, and blood gas
      values. The measurements of vital signs did not differ significantly between the
      2 modes. CONCLUSION: NAVA lowered PIP and reduced respiratory muscle load in
      preterm infants at equivalent inspiratory oxygen fraction and partial pressure of
      CO(2) of capillary blood in comparison with SIMV with PS.

PMID- 22658786
TI  - Dyslipidemia without obesity in indigenous Argentinean children living at high
      altitude.
AB  - OBJECTIVES: To compare the prevalence of cardiovascular disease risk factors in
      Indian children from San Antonio de los Cobres (SAC) and children from Buenos
      Aires (BA), and to examine body mass index (BMI), waist circumference (WC), and
      WC/height as predictors of dyslipidemia in both groups. STUDY DESIGN: Data were
      collected cross-sectionally from BMI, WC, blood pressure, Tanner scale, glucose,
      lipids, and insulin. Dyslipidemia was defined by the National Cholesterol
      Education Program and American Heart Association. RESULTS: The mean ages were
      10.6 +/- 3.0 and 9.5 +/- 2.0 years in SAC vs BA children. Of the 330 SAC
      children, 15 (4.5%) were overweight and 12 (3.6%) obese, and of the 603 BA, 97
      (16.1%) were overweight and 82 (13.6%) obese per Centers for Disease Control.
      There was a significantly higher prevalence of high triglycerides (28.8% vs 3.5%)
      and low high-density lipoprotein cholesterol (30.0% vs 5.5%) in SAC vs BA
      children. The areas under the receiver operating characteristic curve in
      predicting high triglycerides were BMI = 0.55 (95% CI, 0.48-0.62; P = .15) in SAC
      and BMI = 0.65 (95% CI, 0.52-0.77; P = .02) in BA children. Similar results from
      the areas under the receiver operating characteristic curve were obtained when
      low high-density lipoprotein cholesterol was used, indicating that BMI was not a
      significant predictor for dyslipidemia in SAC children. When BMI was replaced by
      WC and WC/height, results were similar. CONCLUSIONS: Anthropometric markers were
      not an acceptable predictor for National Cholesterol Education Program cutoffs
      for dyslipidemia in SAC children. Longitudinal studies should determine if SAC
      children are at high risk for cardiovascular diseases because of genetic
      background.

PMID- 22658787
TI  - Population-based study of incidence and clinical outcome of neonatal cholestasis
      in patients with Down syndrome.
AB  - OBJECTIVE: To study the incidence and outcome of Down syndrome-associated
      neonatal cholestasis in a population-based cohort. STUDY DESIGN: This
      retrospective study included all neonates diagnosed with Down syndrome born
      between January 2005 and September 2011 in the County of Stockholm, Sweden.
      Clinical and biochemical data related to cholestasis, early gastrointestinal (GI)
      involvement, congenital heart defects (CHD), and bone marrow disease were
      obtained from the computer-based hospital chart system. RESULTS: A total of 206
      newborns with Down syndrome were identified, for an incidence of 1 in 880
      newborns. Prevalences of other diseases in these newborns included 47% for CHD,
      11.2% for GI involvement, 3.9% for neonatal cholestasis, and 3.4% for bone marrow
      disease. Neonatal cholestasis was more common in the newborns with GI involvement
      (3 of 23 vs 5 of 183 of those without GI involvement; P = .047), CHD (8 of 96 vs
      0 of 110 of those without CHD; P = .0019), and bone marrow disease (3 of 7 vs 5
      of 199 of those without bone marrow disease; P = .0013). Cholestasis was severe
      in 3 patients (all of whom had bone marrow disease, with liver failure and early
      death in 2), and transient in 5 patients. CONCLUSION: Neonatal cholestasis occurs
      in a significant percentage of patients with Down syndrome and is always
      associated with involvement of other organs. The outcome is variable, being most
      severe in newborns with the combination of neonatal cholestasis and bone marrow
      disease.

PMID- 22658788
TI  - Nonketotic hyperglycinemia presenting as pulmonary hypertensive vascular disease
      and fatal pulmonary edema in response to pulmonary vasodilator therapy.
AB  - The association of pulmonary hypertensive vascular disease with nonketotic
      hyperglycinemia is rare. We describe 5 infants diagnosed with nonketotic
      hyperglycinemia, in whom pulmonary hypertensive vascular disease was the main
      presenting feature, and who developed severe pulmonary edema in response to
      pulmonary vasodilators.

PMID- 22658789
TI  - Hyperparathyroidism, a forgotten cause of musculoskeletal pain.

PMID- 22658790
TI  - Surgical reconstruction and mobilization therapy for a retracted extensor
      hallucis longus laceration and tendon defect repaired by split extensor hallucis
      longus tendon lengthening and dermal scaffold augmentation.
AB  - A reconstructive technique and physical therapy protocol is presented for the
      treatment of extensor hallucis longus (EHL) lacerations with critical size
      defects caused by tendon retraction. The primary goal of treatment was to restore
      EHL structure and function without the use of a bridging allograft or tendon
      transfer. The technique is performed by split lengthening the distal segment of
      the lacerated EHL and rotating the lengthened segment proximally 180 degrees  to
      bridge the tendon defect. The lengthened tendon is then sutured to the proximal
      segment of the EHL. The EHL is then tubularized with an acellular dermal scaffold
      at the region of tendon rotation to improve tendon strength, minimize the
      probability of tendon overlengthening or re-rupture, and improve the tendon
      gliding motion, which can be compromised by the tendon irregularity caused by
      rotation of the tendon. Postoperative range of motion therapy should be initiated
      at 3 weeks postoperatively. A case report of this technique and postoperative
      mobilization protocol is presented. The American Orthopaedic Foot and Ankle
      Society midfoot score at 3 and 6 months postoperatively was 90 of 100. The
      patient regained active dorsiflexion motion of the hallux without functional
      limitations, deformity, or contracture of the hallux. The advantages of this
      technique include that a large cadaveric allograft is not needed to bridge a
      critical size tendon defect and tendon lengthening provides a biologically active
      tendon graft without the secondary comorbidities and dysfunction commonly
      associated with tendon transfer procedures.

PMID- 22658791
TI  - [Surgeon 2.0: the challenge is on the Web].
AB  - Numerous articles and opinions have been published in the last few years on how
      the Internet is changing clinical practice. In this article we focus on
      describing 2 aspects that we believe are fundamental in the web 2.0 and Medicine
      Surgery inter-relationship: a) web 2.0 conceptualisation and its differences with
      other pre-existing tools, and b) a description of some of the tools that from a
      medical-surgical view could be of major interest to the professionals, the
      patients, and interaction between both. The time has arrived to board train 2.0,
      where the channels of communication between the professionals, and between them
      and the patients, are improving disease situations daily, to improve learning
      through contact with other physicians and surgeons, at the same time providing an
      excellent resource for maintaining health and to know the disease and its
      treatment.

PMID- 22658792
TI  - Pathological roles of invadopodia in cancer invasion and metastasis.
AB  - Invadopodia are actin-rich membrane protrusions formed by invasive cancer cells.
      Invadopodia mediate the focal degradation of pericellular extracellular matrix
      (ECM) by the localized proteolytic activity of matrix metalloproteinases (MMPs).
      Over the last 2 decades, much progress has been made in identifying the molecular
      components of invadopodia and understanding the molecular mechanisms underlying
      their formation. Although the physiological and pathological roles of invadopodia
      have long been elusive, emerging evidence has begun to reveal their importance in
      local invasion during cancer metastasis. This review highlights recent findings
      on the roles of invadopodia in cancer invasion and metastasis and discusses the
      possibility of and strategies for targeting invadopodia formation for the
      development of novel anticancer therapeutics.

PMID- 22658793
TI  - On non-invasive 2D and 3D Chromatic White Light image sensors for age
      determination of latent fingerprints.
AB  - The feasibility of 2D-intensity and 3D-topography images from a non-invasive
      Chromatic White Light (CWL) sensor for the age determination of latent
      fingerprints is investigated. The proposed method might provide the means to
      solve the so far unresolved issue of determining a fingerprints age in forensics.
      Conducting numerous experiments for an indoor crime scene using selected
      surfaces, different influences on the aging of fingerprints are investigated and
      the resulting aging variability is determined in terms of inter-person, intra
      person, inter-finger and intra-finger variation. Main influence factors are shown
      to be the sweat composition, temperature, humidity, wind, UV-radiation, surface
      type, contamination of the finger with water-containing substances, resolution
      and measured area size, whereas contact time, contact pressure and smearing of
      the print seem to be of minor importance. Such influences lead to a certain
      experimental variability in inter-person and intra-person variation, which is
      higher than the inter-finger and intra-finger variation. Comparing the aging
      behavior of 17 different features using 1490 time series with a total of 41,520
      fingerprint images, the great potential of the CWL technique in combination with
      the binary pixel feature from prior work is shown. Performing three different
      experiments for the classification of fingerprints into the two time classes [0,
      5 h] and [5, 24 h], a maximum classification performance of 79.29% (kappa=0.46)
      is achieved for a general case, which is further improved for special cases. The
      statistical significance of the two best-performing features (both binary pixel
      versions based on 2D-intensity images) is manually shown and a feature fusion is
      performed, highlighting the strong dependency of the features on each other. It
      is concluded that such method might be combined with additional capturing
      devices, such as microscopes or spectroscopes, to a very promising age estimation
      scheme.

PMID- 22658794
TI  - Forensic archaeoentomology--An insect fauna from a burial in York Minster.
AB  - An insect fauna associated with the medieval burial of Archbishop Greenfield,
      interred in December 1315 in a lead coffin within a stone sarcophagus beneath the
      floor of York Minster, is examined and compared with the limited entomological
      data from other medieval burials. The implications of the archaeoentomological
      data are discussed. The fauna is dominated by the so-called coffin beetle
      Rhizophagus parallelocollis and the generalised staphylinid predator Quedius
      mesomelinus, together with a number of subterranean fungal feeders. The beetle
      assemblage is probably immediately post burial, and the lead coffin in the case
      of Greenfield had not been able to shield the body from decay.

PMID- 22658795
TI  - Estimating shot distance from limited pellets pattern.
AB  - Several methods are available for shooting range estimation based on pellets
      pattern on the target that have a remarkable degree of accuracy. The task is
      usually approached working under the assumption that the entire distribution of
      pellets is available for examination. These methods fail, however, when the
      victim has been hit by a portion of the pattern only. The problem can be solved
      with reasonable accuracy when there are areas of void in the victim that are
      adjacent to the area struck by pellets. This study presents a method that can be
      used in precisely this type of situation, allowing the estimation of shot
      distance in cases of partial pellet patterns. It is based on collecting
      distributions in test shots at several distances, and taking samples in the
      targets, constrained by the shape of the void and the pellet hit areas.
      Statistical descriptors of patterns are extracted from such samples, and fed into
      a neural network classifier, estimating shot ranges of distance.

PMID- 22658796
TI  - Clinical and molecular characterization of a rare 2.4 kb deletion causing
      alpha(+) thalassemia in a Chinese family.

PMID- 22658799
TI  - A long-lasting dendritic cell DNA vaccination system using lysinylated
      amphiphiles with mannose-mimicking head-groups.
AB  - Dendritic cells (DCs) pulsed/transduced with tumor-associated or viral antigens
      have shown promise in combating cancer and infectious diseases. Despite
      significant progresses, development of a biologically safe DC-based genetic
      immunization (DNA vaccination) system capable of providing truly long-lasting
      protective immunity remains a significant scientific challenge. Here we show that
      immunization with autologous DCs pre-transfected with electrostatic complexes
      (lipoplexes) of a plasmid DNA encoding melanoma tumor associated antigen and
      liposomes of two lysinylated cationic amphiphiles with mannose-mimicking quinic
      and shikimic acid head-groups provides long-lasting (300 days post tumor
      challenge) protective immunity with significant memory response (more than six
      months after the second tumor challenge) in more than 80% immunized mice. The
      presently described non-viral ex vivo DC-transfection system may be exploited in
      inducing long-lasting immune response in DC-based genetic immunization.

PMID- 22658800
TI  - Transplantation of an alginate-matrigel matrix containing isolated ovarian cells:
      first step in developing a biodegradable scaffold to transplant isolated
      preantral follicles and ovarian cells.
AB  - For women diagnosed with leukemia, transplantation of cryopreserved ovarian
      tissue after disease remission is not advisable. Therefore, to restore fertility
      in these patients, we aim to develop a biodegradable artificial ovary that offers
      an environment where isolated follicles and ovarian cells (OCs) can survive and
      grow. Four NMRI mice were ovariectomized and their ovaries used to isolate OCs.
      Groups of 50,000 OCs were embedded in an alginate-matrigel matrix for further
      fixation (fresh controls), one week of in vitro culture (IVC) or heterotopic
      autografting. OC proliferation (Ki67), apoptosis (TUNEL), scaffold degradation,
      vessel formation (CD34) and inflammation (CD45) were analyzed. Ki67-positive OCs
      were found in 2.3%, 9.0% and 15.5% cells of cases in fresh, IVC and grafted beads
      respectively, while cells were TUNEL-positive in 0%, 1.5% and 6.9% of cases.
      After IVC or grafting, the beads degraded, losing their original round aspect,
      and infiltrating blood capillaries could be observed in the grafted beads. CD34
      positive cells and 22% CD45-positive cells were found around and inside the
      matrix. In conclusion, our results demonstrate that an alginate-based matrix is a
      promising proposition to graft isolated OCs. After transplantation, this matrix
      was able to degrade, allowed vascularization and elicited a low inflammatory
      response.

PMID- 22658797
TI  - Prevalence of hepatitis C virus infection among human immunodeficiency virus-1
      infected pregnant women in Malawi: the BAN study.
AB  - BACKGROUND: In Sub-Saharan Africa, prevalence estimates of hepatitis C virus
      (HCV) vary widely. OBJECTIVES: To assess the prevalence of HCV infection among
      HIV-infected, pregnant women screened for a large clinical trial in Lilongwe,
      Malawi. STUDY DESIGN: Plasma from 2041 HIV-infected, pregnant women was screened
      for anti-HCV IgG using a chemiluminiscent immunometric assay (CIA). Specimens
      with a signal-cut-off ratio>=1.00 were considered reactive and those with S/Co
      ratio<1.00 non-reactive. All CIA-reactive specimens were tested by a recombinant
      immunoblot assay (RIBA) for anti-HCV and by PCR for HCV RNA. RESULTS: Of 2041
      specimens, 110 (5.3%, 95% CI: 4.5-6.5%) were CIA reactive. Of the 109 CIA
      reactive specimens available for RIBA testing, 2 (1.8%) were positive, 28 (25.7%)
      were indeterminate, and 79 (72.5%) were negative. All CIA-reactive specimens were
      HCV RNA negative (n=110). The estimated HCV prevalence based on the screening
      assay alone was 5.3%; based on supplemental RIBA testing, the status of HCV
      infection remained indeterminate in 1.4% (28/2040, 95% CI: 0.1-2.0) and the
      prevalence of confirmed HCV infections was 0.1% (2/2040, 95% CI: 0-0.4%).
      CONCLUSIONS: HCV seroprevalence among HIV-infected, pregnant women in Malawi
      confirmed by supplemental RIBA HCV 3.0 is low (0.1%); CIA showed a high false
      reactivity rate in this population.

PMID- 22658801
TI  - Controllable synthesis of hollow bipyramid beta-MnO(2) and its high
      electrochemical performance for lithium storage.
AB  - Three types of MnO2 nanostructures, viz., alpha-MnO2 nanotubes, hollow beta-MnO2
      bipyramids, and solid beta-MnO2 bipyramids, have been synthesized via a simple
      template-free hydrothermal method. Cyclic voltammetry and galvanostatic
      charge/discharge measurements demonstrate that the hollow beta-MnO2 bipyramids
      exhibit the highest specific capacity and the best cyclability; the capacity
      retains 213 mAh g(-1) at a current density of 100 mA g(-1) after 150 cycles. XRD
      patterns of the lithiated beta-MnO2 electrodes clearly show the expansion of
      lattice volume caused by lithiation, but the structure keeps stable during
      lithium insertion/extraction process. We suggest that the excellent performance
      for beta-MnO2 can be attributed to its unique electrochemical reaction, compact
      tunnel-structure and hollow architecture. The hollow architecture can accommodate
      the volume change during charge/discharge process and improve effective diffusion
      paths for both lithium ions and electrons. 

PMID- 22658802
TI  - Next generation of antimicrobial peptides as molecular targeted medicines.
AB  - Antibiotics have significantly improved our living environments. However, overuse
      of antibiotics has led to the emergence of multi-drug resistant microorganisms,
      and the subsequent constant demand for the exploration of novel antibiotics. To
      this end, antimicrobial peptides (AMPs) have attracted much attention as a novel
      class of antibiotics. AMPs have strong antimicrobial activity against a wide
      range of species, including gram-positive and gram-negative bacteria, fungi, and
      viruses. In addition, they are also effective against pathogenic organisms that
      are resistant to conventional drugs. Despite their great potential, the hemolytic
      activity and a highly broad spectrum of activity of AMPs dictate the need for
      amendments to develop safe pharmaceuticals. The human body contains commensal
      microflora as an integral part of complex mucosal surfaces that offers protection
      against pathogenic organisms. Administration of antibiotics with broad spectra of
      activity disrupts the indigenous microflora and increases the risks of diarrhea
      and other fatal infections. Therefore, it is difficult, but vital, to develop
      treatments capable of rapidly eliminating pathogenic organisms while maintaining
      the commensal microbiota. As such, novel pharmaceuticals, safe designer AMPs have
      been heavily researched. In this article, we review recent attempts to spatially
      and temporally regulate AMPs to enhance the quality-of-life of patients.

PMID- 22658803
TI  - Generation of superoxide anions by a glycation reaction in conventional
      laboratory media.
AB  - We reported that generation of superoxide anion (O(2)(-)) was detected from
      conventional laboratory media. The generated O(2)(-) is non-enzymatic converted
      to hydroxyl radicals, which cause damage to lipids, proteins, and nucleic acids.
      However, the O(2)(-) generating mechanism from culture media is unclear. We
      considered that the O(2)(-) generation was implicated in a glycation reaction
      between reducing sugar and proteins, which is the early stage of Maillard
      reaction. It has been suggested that the glycated proteins, such as Schiff base
      and Amadori compounds, undergo a spontaneous autoxidation reaction, catalyzed by
      transition metal ions, involving the O(2)(-) generation. Therefore, we
      investigated the effect of Chelex 100 on the O(2)(-) generation from brain-heart
      infusion (BHI) medium, which is a nutritional culture medium for bacteria.
      However, the O(2)(-) generation from the BHI medium treated with Chelex 100 was
      significantly increased in comparison to it treated without Chelex 100. The
      quantity of O(2)(-) generation from BHI medium was significantly increased by
      addition of glucose, and in alkaline environment as well as a glycation reaction
      model system that autoclaved a mixture solution of glucose and tryptophan. In
      addition, the O(2)(-) generation from BHI medium was significantly inhibited by
      pyridoxamine that is a Maillard reaction inhibitor. Therefore, it was suggested
      that the O(2)(-) generation from BHI medium is closely related to the glycation
      reaction of amide compounds such as proteins containing in the medium without the
      transition metals.

PMID- 22658798
TI  - Prevalence of hepatitis C virus variants resistant to NS3 protease inhibitors or
      the NS5A inhibitor (BMS-790052) in hepatitis patients with genotype 1b.
AB  - BACKGROUND: Hepatitis C virus (HCV) of genotype 1b is the most prevalent
      worldwide, and the least responsive to interferon-based treatments. A combination
      therapy with two direct-acting antivirals has shown promising results in patients
      with HCV-1b, but the prevalence of drug-resistant variants before treatment is
      not known in the Japanese population. OBJECTIVES: To detect HCV variants
      resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in
      hepatitis patients infected with HCV-1b. STUDY DESIGN: Drug-resistant mutations
      were determined in the 362 hepatitis patients infected with HCV-1b who had not
      received direct-acting antivirals before. RESULTS: Amino-acid substitutions
      resistant to NS3 inhibitors (V36A, T54S, Q80H and D168E) were detected in 15 of
      the 307 (4.9%) patients, who had been examined, and T54S (3.3%) predominated over
      V36A (0.3%), Q80R (0.7%) and D168E (0.7%) in them. Amino-acid substitutions
      resistant to BMS-790052 (L31M and/or Y93H) were detected in 33 of the 294 (11.2%)
      patients, and Y93H (8.2%) predominated over L31M (2.7%). One of the 239 (0.4%)
      patients, who had been examined for amino-acid substitutions in both NS3 and NS5A
      regions, possessed HCV-1b variants resistant to NS3 inhibitors (T54S) and BMS
      790052 (L31M). CONCLUSIONS: Mutations conferring resistance to NS3 inhibitors or
      BMS-790052 were frequent in our treatment-naive study population, but double
      mutants with possible resistance to both drugs were rare. Since single mutations
      did not result in treatment failure in a previous pilot trial combining BMS
      790052 and an NS3 inhibitor, larger trials of this drug regimen appear warranted
      in the Japanese population.

PMID- 22658804
TI  - The role of Wt1 in regulating mesenchyme in cancer, development, and tissue
      homeostasis.
AB  - From both the fundamental and clinical perspectives, there is growing interest in
      mesenchymal cells and the mechanisms that regulate the two-way switch between
      mesenchymal and epithelial states. Here, we review recent findings showing that
      the Wilms' tumor gene (Wt1) is a key regulator of mesenchyme maintenance and the
      mesenchyme to epithelial balance in the development of certain mesodermal organs.
      We summarize recent experiments demonstrating, unexpectedly, that Wt1 is also
      essential for the integrity or function of multiple adult tissues, mainly, we
      argue, through regulating mesenchymal cells. We also discuss growing evidence
      that implicates Wt1 in tissue repair and regeneration. Drawing on these findings,
      we highlight the similarities between Wt1-expressing cells in different tissues.
      We believe that future studies aimed at elucidating the mechanisms underlying the
      functions of Wt1 in adult cells will reveal key cell types, pathways, and
      molecules regulating adult tissue homeostasis and repair.

PMID- 22658805
TI  - Onset of segmental colitis associated with diverticulosis after treatment with
      bevacizumab for metastatic colorectal carcinoma.

PMID- 22658806
TI  - Prenatal exposure to organomercury, thimerosal, persistently impairs the
      serotonergic and dopaminergic systems in the rat brain: implications for
      association with developmental disorders.
AB  - Thimerosal, an organomercury compound, has been widely used as a preservative.
      Therefore, concerns have been raised about its neurotoxicity. We recently
      demonstrated perturbation of early serotonergic development by prenatal exposure
      to thimerosal (Ida-Eto et al. (2011) [11]). Here, we investigated whether
      prenatal thimerosal exposure causes persistent impairment after birth. Analysis
      on postnatal day 50 showed significant increase in hippocampal serotonin
      following thimerosal administration on embryonic day 9. Furthermore, not only
      serotonin, striatal dopamine was significantly increased. These results indicate
      that embryonic exposure to thimerosal produces lasting impairment of brain
      monoaminergic system, and thus every effort should be made to avoid the use of
      thimerosal.

PMID- 22658807
TI  - Correlation between Ki-67 immunohistochemistry and 18F-fluorothymidine uptake in
      patients with cancer: A systematic review and meta-analysis.
AB  - BACKGROUND: Positron emission tomography (PET) imaging using the radiotracer 18F
      Fluorothymidine (FLT) has been proposed as an imaging biomarker of tumour
      proliferation. If FLT-PET can be established as such it will provide a non
      invasive, quantitative measurement of tumour proliferation across the entire
      tumour. Results from validation studies have so far been conflicting with some
      studies confirming a good correlation between FLT uptake and Ki-67 score and
      others presenting negative results. METHODS: Firstly we performed a systematic
      review of published studies between 1998 and 2011 that explored the correlation
      between FLT uptake and Ki-67 score and examined possible variations in the
      methods used. Studies were eligible if they: (a) included patients with cancer,
      (b) investigated the correlation between Ki-67 measured by immunohistochemistry
      and FLT uptake measured with PET scanning, and (c) were published as a full paper
      in a peer-reviewed scientific journal. Secondly a meta-analysis of the
      correlation coefficient values reported from each study was performed.
      Correlation coefficient (r) values were extracted from each study and 95%
      confidence intervals (CIs) were calculated after applying Fisher's z
      transformation. For subgroup analysis, studies were classified by the index used
      to characterise Ki-67 expression (average or maximum expression), the nature of
      the sample (whole specimen or biopsy) and the cancer type. FINDINGS: Twenty-seven
      studies were identified as eligible for the meta-analysis. In the studies we
      examined there were variations in aspects of the methods and reporting. The meta
      analysis showed that given an appropriate study design the FLT/Ki-67 correlation
      is significant and independent of cancer type. Specifically subgroup analysis
      showed that FLT/Ki-67 correlation was high in studies measuring the Ki-67 average
      expression regardless of use of surgery or biopsy samples (r=0.70, 95% CI=0.43
      0.86, p<0.001). Of the studies that measured Ki-67 maximum expression, only those
      that used the whole surgical specimen provided a significant r value (r=0.72, 95%
      CI=0.54-0.84, p<0.001). Studies that used biopsy samples for Ki-67 maximum
      measurements did not produce a significant r value (r=0.04, 95% CI=-0.18-0.26,
      p=0.71). In terms of the cancer type subgroup analysis there is sufficient data
      to support a strong FLT/Ki-67 correlation for brain, lung and breast cancer. No
      publication bias was detected. INTERPRETATION: This systematic review and meta
      analysis highlights the importance of the methods used in validation studies
      comparing FLT-PET imaging with the biomarker Ki-67. The correlation is
      significant and independent of cancer type provided a study design that uses Ki
      67 average measurements, regardless of nature of sample, or whole surgical
      samples when measuring Ki-67 maximum expression. Sufficient data to support a
      strong correlation for brain, lung and breast cancer exist. However, larger,
      prospective studies with improved study design are warranted to validate these
      findings for the rest of the cancer types.

PMID- 22658809
TI  - Atmospheric mercury deposition recorded in an ombrotrophic peat core from
      Xiaoxing'an Mountain, Northeast China.
AB  - The historical mercury accumulation rates (Hg AR) resulting from atmospheric
      deposition to Xiaoxing'an Mountain were determined via analysis of (210)Pb- and
      (14)C-dated cores up to 5000 years old. Natural Hg AR background, pre-industrial
      Hg AR and maximum industrial Hg AR in Northeast China were 2.2 +/-1.0 MUg/m(2)/yr
      for 5100-4500 BP, 5.7 MUg/m(2)/yr and 112.4 MUg/m(2)/yr, respectively. We assumed
      that the increase in Hg deposition in the Xiaoxing'an mountain area during
      industrial time was mainly attributed to local anthropogenic emissions around
      this peat bog.

PMID- 22658808
TI  - A nomogram to predict individual prognosis in node-negative breast carcinoma.
AB  - BACKGROUND: Currently, the benefit of chemotherapy (CT) in node-negative breast
      carcinoma (NNBC) is discussed. The evaluation of classical clinical and
      histological factors is limited to assess individual outcome. A statistical model
      was developed to improve the prognostic accuracy of NNBC. METHODS: A total of 305
      node-negative breast carcinomas who underwent surgery (+/- radiotherapy) but no
      adjuvant treatment were selected. Putative prognosis factors including age,
      tumour size, oestrogen receptor (ER), progesterone receptor (PgR), Scarff-Bloom
      Richardon (SBR) grading, urokinase plasminogen activator (uPA), plasminogen
      activator inhibitor 1 (PAI-1) and thymidine kinase (TK) were evaluated. The
      developed model was internally validated using Harrell's concordance index. A
      prognosis index (PI) was proposed and compared with Adjuvant! Online program.
      RESULTS: Age (p < 0.001), pathological tumour size (pT) (p < 0.001), PgR (p =
      0.02), and PAI-1 (p <= 0.001) were included in the Cox regression model
      predicting Breast cancer specific survival (BCSS) at 5-years. Internal validation
      revealed a concordance index of 0.71. A PI score was derived from our nomogram.
      The PI score was significantly associated with BCSS (hazard ratio (HR): 4.1 for
      intermediate, p=0.02, HR: 8.8, p < 0.001 for high group) as compared to Adjuvant!
      Online score (HR: 1.4, p=0.14). CONCLUSION: A nomogram can be used to predict
      probability survival curves for individual breast cancer patients.

PMID- 22658810
TI  - Perioperative cardiac evaluation of simulated patients by practicing
      anesthesiologists is not consistent with 2007 ACC/AHA guidelines.
AB  - STUDY OBJECTIVE: To determine if practicing anesthesiologists recommend
      preoperative evaluations consistent with the 2007 ACC/AHA guidelines on
      perioperative care. DESIGN: Survey instrument. SETTING: Academic medical center.
      SUBJECTS: ASA membership. MEASUREMENTS: In this Web-based survey, participants
      were presented with 6 clinical scenarios characterized by surgical procedure and
      the patient's clinical condition (ie, clinical risk factors and functional
      capacity). Scenarios and possible recommendations were presented randomly.
      Participants were asked to select the recommendation they considered to be most
      consistent with the Guidelines. The percentage of participants selecting the
      recommendation most consistent with the 2007 Guidelines was recorded. MAIN
      RESULTS: Of the 22,504 actively practicing members of the ASA who were sent a
      survey, 1,595 actively practicing self-selected anesthesiologists responded. For
      one of 6 scenarios, patients with an active cardiac condition, the upper 95%
      confidence bound for the percent selecting a recommendation consistent with the
      Guidelines was 82%. For the remaining 5 scenarios, the upper 95% confidence bound
      for the percent of anesthesiologists with an appropriate recommendation did not
      exceed 40%. With the exception of the scenario describing a patient with an
      active cardiac condition, respondents were more likely to provide recommendations
      consistent with the Guidelines if they had been in practice less than 5 years or
      worked in a teaching environment. CONCLUSION: When evaluating simulated patients,
      practicing anesthesiologists who are ASA members did not recommend preoperative
      evaluations that were consistent with the 2007 ACC/AHA Guidelines.

PMID- 22658811
TI  - Study design features affecting outcome in antidepressant trials.
AB  - BACKGROUND: A key issue in the approval process of antidepressants is the
      inconsistency of results between antidepressant clinical phase III trials.
      Identifying factors influencing efficacy data is needed to facilitate
      interpretation of the results. METHODS: We reviewed data packages submitted as
      new drug applications to Swissmedic focusing on pivotal, short-term
      antidepressant trials. Included studies used HAMD-17 or HAMD-21 as primary
      measures and enrolled patients aged 18-65 years with a diagnosis of major
      depression. Due to the hierarchical structure of the data a mixed-effect
      regression model has been applied with responder rates as primary outcome
      criterion. Random intercepts were estimated for the different trials, while study
      design factors were assigned as explanatory fixed effects. RESULTS: The final
      dataset was based upon 35 study reports with a total of N=10,835 patients.
      Significant results were found for study arm (placebo vs. active compound,
      p<0.001), sample size (p=0.002), duration of treatment (p=0.024), two or more
      active treatment arms (p=0.022) and the individual drug (p=0.029). Furthermore, a
      tendency to an association with the outcome was observed for baseline disease
      severity (p=0.077) and possibility of dosing adaptation (p=0.076). LIMITATIONS:
      Due to strict confidentiality agreements, individual drugs are not reported here.
      Further research should consider additional variables that might have an impact
      on the results of antidepressant trials. CONCLUSIONS: Efficacy data in
      antidepressant trials is significantly affected by various factors. These factors
      and their potentially confounding role have to be considered in the
      interpretation of the results.

PMID- 22658812
TI  - Validation of prognostic factors in malignant pleural mesothelioma: a
      retrospective analysis of data from patients seeking compensation from the New
      South Wales Dust Diseases Board.
AB  - INTRODUCTION: We aimed to examine the prognostic values of established risk
      factors and to validate the prognostic value of the neutrophil-to-lymphocyte
      ratio (NLR) in an independent series of patients with malignant pleural
      mesothelioma (MPM). PATIENTS AND METHODS: A total of 148 patients who applied for
      compensation at the Dust Diseases Board from 2007 to 2009 were included in this
      study. Overall survival was determined by the Kaplan-Meier method, and NLR was
      defined as the absolute neutrophil divided by the lymphocyte count. The
      prognostic value of the variables was examined by using Cox regression analysis,
      and all factors were entered into a multivariate model to determine their
      independent effect. RESULTS: The patient characteristics were median age of 73
      years; 93% men; 59% epithelial subtype; median NLR of 3.5 at diagnosis (n = 79);
      median overall survival of 10.6 months. The following variables were predictive
      of longer overall survival in univariate analysis: younger age, epithelial
      subtype, lower tumor stage, low white cell count, low platelet count, low
      hemoglobin level, and low NLR. Multivariate analysis confirmed that nonepithelial
      vs. epithelial subtype (hazard ratio [HR], 3.0; P < .001), tumor stage (HR, 1.6;
      P < .001), hemoglobin level difference >=10 vs. <10 (HR, 2.0; P = .03), no
      chemotherapy vs. use of chemotherapy (HR, 2.4; P < .001), and NLR >=3 vs. <3 (HR,
      2.2; P < .01) were independently associated with prognosis. CONCLUSIONS: Apart
      from previously recognized factors, such as histosubtype, tumor stage, and
      hemoglobin level difference, NLR, an index of systemic inflammation bears
      prognostic significance that shows that a snapshot of immune status is able to
      convey important prognostic information.

PMID- 22658813
TI  - Association between polymorphisms in COMT, PLCH1, and CYP17A1, and non-small-cell
      lung cancer risk in Chinese nonsmokers.
AB  - BACKGROUND: Recently, polymorphisms in COMT (catechol-O-methyltransferase), PLCH1
      (phosphoinositide-specific phospholipase C eta 1), and CYP17A1 (cytochrome P450
      17A1) were found to be associated with the development of lung cancer in a non
      Chinese population. AIMS: To explore the potential association between single
      nucleotide polymorphism (SNP) in COMT, PLCH1, CYP17A1, and non-small-cell lung
      cancer (NSCLC) susceptibility in Chinese patients who were nonsmokers. METHODS: A
      case-controlled study was conducted in 200 patients with NSCLC and 200 healthy
      controls who were age and sex matched. SNPs rs4680, rs181696, and rs743572 from
      the COMT, PLCH1, and CYP17A1 genes, respectively, were selected for genotyping.
      The association between genotype and lung cancer risk was evaluated by computing
      the odds ratio and 95% confidence interval from multivariate unconditional
      logistic regression analyses with adjustment for sex and age. RESULTS: The
      frequency of the G genotype in COMT rs4680 was statistically different between
      patients with NSCLC and controls (P = .04), and between patients with
      adenocarcinomas (ADC) and controls (P = .02). The frequency of the A genotype in
      PLCH1 rs181696 occurred more frequently in squamous cell carcinomas (SQC) than in
      controls (P = .02). The G/G homozygous genotype in COMT rs4680 and A/A homozygous
      genotype in PLCH1 rs181696 were associated with ADC and SQC, respectively (odds
      ratio [OR] 0.61 and OR 2.01, respectively). CONCLUSION: In this study, we found
      that the COMT rs4680 SNP was significantly associated with a reduced risk of
      NSCLC, especially ADC, which suggests that this SNP may have a protective effect.
      Moreover, the PLCH1 rs181696 SNP was strongly associated with an increased risk
      of SQC, which suggests that this SNP may be a risk factor for developing SQC.

PMID- 22658814
TI  - A phase I open-label dose-escalation study of intravenous BI 2536 together with
      pemetrexed in previously treated patients with non-small-cell lung cancer.
AB  - INTRODUCTION: BI 2536 is a potent, highly selective inhibitor of polo-like kinase
      (Plk) 1. This open-label, phase I study investigated the maximum tolerated dose
      (MTD), safety, efficacy, and pharmacokinetics (PK) of BI 2536 IV in combination
      with standard-dose pemetrexed in previously treated advanced or metastatic non
      small-cell lung cancer. PATIENTS AND METHODS: A standard 3 + 3 design was used.
      The patients received 500 mg/m(2) pemetrexed and escalating doses of BI 2536 on
      day 1 every 3 weeks. The primary objective was the MTD of BI 2536 combined with
      pemetrexed. Secondary endpoints were response rate (Response Evaluation Criteria
      in Solid Tumors), overall safety, and PK. RESULTS: Forty-one patients received BI
      2536 (100-325 mg). Two dose-limiting toxicities (DLT) occurred at BI 2536 325 mg
      (grade 3 pruritus and rash; grade 4 neutropenia). Therefore, the MTD for BI 2536
      in combination with pemetrexed was 300 mg. After expanding the MTD dose level, 3
      additional patients experienced DLTs, which resulted in expansion of the 250 mg
      cohort, in which 4 of the 13 additional patients experienced DLTs. Therefore, the
      recommended dose of BI 2536 was 200 mg. Most frequently reported drug-related
      adverse events were fatigue (71%), nausea (37%), and rash (34%). Two patients had
      durable confirmed partial responses; 21 (54%) patients had stable disease after
      the treatment cycle 2. PK analysis showed that BI 2536 and pemetrexed exposure
      were not altered when coadministered. CONCLUSION: BI 2536 200 mg combined with
      standard-dose pemetrexed has an acceptable safety profile in relapsed non-small
      cell lung cancer. The antitumor activity observed is encouraging and supports
      further investigation of Plk inhibitors.

PMID- 22658815
TI  - Classifying responders and non-responders; does it help when there is evidence of
      differentially responding patient groups?
AB  - INTRODUCTION: Continuous trial outcomes are often dichotomized into 'response'
      and 'non-response' categories prior to statistical analysis. This facilitates the
      interpretation of results, but generally reduces statistical power. Exceptions
      may occur when response in the study population is heterogeneous, and outcomes
      are bimodally distributed. We explore whether bimodality is present in
      antidepressant trial data and whether dichotomizing then indeed results in more
      powerful statistical tests. METHODS: The distributions of relative changes from
      baseline (rCFB) on the Hamilton depression rating scale (HAM-D) were estimated
      using pooled data from nine antidepressant trials. T-tests on rCFB scores and chi
      square tests on dichotomized outcomes were compared to assess the consequences of
      dichotomization, using both the commonly applied cutoff (i.e. rCFB > 50%) and an
      estimated cutoff that provided optimal separation of the mixture of two normal
      distributions that best fitted the pooled placebo outcomes. The power of both
      tests was also evaluated for simulated scenario's that varied the degree of
      bimodality and the treatment effect and sample size. RESULTS: Placebo and
      treatment groups showed evidence of bimodality. The estimated cutoff closely
      matched the commonly applied cutoff. Nevertheless, t-tests generally yielded
      smaller p-values than chi-square tests. Simulations showed that dichotomization
      only provides superior power when bimodality was considerably more marked than
      observed in the empirical data. CONCLUSION: Antidepressant trial outcomes showed
      bimodality, suggesting differential response among patient groups. This
      heterogeneity in outcome distributions should be reported more often, since a
      comparison of means does not adequately summarize the differences between
      treatment groups. However, simply dichotomizing outcomes is not an appropriate
      alternative as it reduces statistical power.

PMID- 22658817
TI  - Methylmalonic acidemia and hyperglycemia: an unusual association.

PMID- 22658816
TI  - The stearoyl-acyl-carrier-protein desaturase promoter (Des) from oil palm confers
      fruit-specific GUS expression in transgenic tomato.
AB  - The stearoyl-acyl-carrier-protein (ACP) desaturase is a plastid-localized enzyme
      that catalyzes the conversion of stearoyl-ACP to oleoyl-ACP and plays an
      important role in the determination of the properties of the majority of cellular
      glycerolipids. Functional characterization of the fatty acid desaturase genes and
      their specific promoters is a prerequisite for altering the composition of
      unsaturated fatty acids of palm oil by genetic engineering. In this paper, the
      specificity and strength of the oil palm stearoyl-ACP desaturase gene promoter
      (Des) was evaluated in transgenic tomato plants. Transcriptional fusions between
      5' deletions of the Des promoter (Des1-4) and the beta-glucuronidase (GUS)
      reporter gene were generated and their expression analyzed in different tissues
      of stably transformed tomato plants. Histochemical analysis of the Des promoter
      deletion series revealed that GUS gene expression was confined to the tomato
      fruits. No expression was detected in vegetative tissues of the transgenic
      plants. The highest levels of GUS activity was observed in different tissues of
      ripe red fruits (vascular tissue, septa, endocarp, mesocarp and columella) and in
      seeds, which harbored the promoter region located between -590 and +10. A
      comparison of the promoter-deletion constructs showed that the Des4 promoter
      deletion (314bp) produced a markedly low level of GUS expression in fruits and
      seeds. Fluorometric analysis of the GUS activity revealed a 4-fold increase in
      the activity of the full-length Des promoter compared to the CaMV35S promoter.
      RNA-hybridization analyses provided additional evidence of increased GUS
      expression in fruits driven by a Des fragment. Taken together, these results
      demonstrate the potential of the Des promoter as a tool for the genetic
      engineering of oil palms and other species, including dicots, in improving the
      quality and nutritional value of the fruits.

PMID- 22658818
TI  - Hallmarks in the history of cerebral palsy: from antiquity to mid-20th century.
AB  - Cerebral palsy (CP) is a term that has been applied over the years to a group of
      children with motor disability and related service requirements. The first
      conceptions of cerebral palsy and our knowledge about aetiology and pathogeny
      allow us to assume that cerebral palsy existed in the Ancient World. Although
      there is lack of detailed medical descriptions from before the 19th century,
      mentions to cerebral palsy can be found in representational art, literary sources
      and paleopathology; however, because of the poor medical documentation, the
      diagnosis of cerebral palsy must remain a more or less well-justified
      supposition. In the Ancient World, the first medical description of cerebral
      palsy was made by Hippocrates in his work "Corpus Hippocraticum". Concrete
      examples and definitions of cerebral palsy, however, did not emerge until the
      early 19th century with observations by William John Little; thus, Little was the
      first personality to intensely engage cerebral palsy. Towards the end of the 19th
      century, two more personalities emerged, adding to the historical hallmarks of
      cerebral palsy: William Osler and Sigmund Freud. The significant developments
      that have followed since then are all due to the contributions of these three
      personalities in the field of cerebral palsy.

PMID- 22658819
TI  - Cortical sources of resting state EEG rhythms are abnormal in dyslexic children.
AB  - OBJECTIVE: Previous studies have been inconclusive whether dominant resting state
      alpha rhythms differ in amplitude in dyslexic subjects when compared to control
      subjects, being these rhythms considered as a reflection of effective cortical
      neural synchronization and cognition. Here we used a validated EEG source
      estimation to test the hypothesis that resting state alpha rhythms are abnormal
      in dyslexic subjects and are related to reading deficits. METHODS: Eyes-closed
      resting state electroencephalographic (EEG) data were recorded in 26 dyslexics
      (12 males, mean age of 11 years +/- 0.5 standard error of mean, SEM) and 11 age
      matched normal control subjects (8 males, mean age of 11 years +/- 0.7 SEM). EEG
      rhythms of interest, based on individual alpha frequency peak, were the
      following: about 2-4 Hz (delta), 4-6 Hz (theta), 6-8 Hz (alpha 1), 8-10 Hz (alpha
      2), and 10-12 Hz (alpha 3). For the higher frequencies, we selected beta 1 (13-20
      Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). Cortical EEG sources were estimated
      by low resolution electromagnetic tomography (LORETA). LORETA solutions were
      normalized across all voxels and frequencies. RESULTS: Compared to the control
      children, the dyslexics showed lower amplitude of parietal, occipital, and
      temporal alpha 2 and alpha 3 sources. In the dyslexics, some of these sources
      were correlated to reading time of pseudo-words (parietal alpha 2, r=-0.56,
      p=0.02; parietal alpha 3, r=-0.58, p=0.02; temporal alpha 3, r=-0.57, p=0.02);
      the higher the alpha power, the shorter the reading time. CONCLUSIONS: Dyslexic
      children are characterized by limited abnormalities of resting state EEG rhythms
      as to topography (posterior regions) and frequency (alpha), which were related to
      phonological encoding (pseudo-words reading). SIGNIFICANCE: Dyslexia may be
      associated to some functional impairment of cortical neuronal synchronization
      mechanisms involved in the resting state condition.

PMID- 22658820
TI  - Tendon structure changes after maximal exercise in the Thoroughbred horse: use of
      ultrasound tissue characterisation to detect in vivo tendon response.
AB  - Investigations into the response of the superficial digital flexor tendon (SDFT)
      of the Thoroughbred horse to mechanical stimuli have been limited to in vitro
      cell culture studies focused primarily on gene expression of critical matrix
      proteins. It is uncertain how well in vitro outcomes translate to the tendon of
      the horse during exercise. The current study examined changes in tendon structure
      in response to maximal exercise using ultrasound tissue characterisation (UTC) to
      scan the SDFT prior to and after competitive racing. UTC uses contiguous
      transverse ultrasound images to assess the dynamics of the echopattern, which has
      a close relationship with changes in the 3-D ultra-structure of the tendon. Using
      UTC, it was possible to detect subtle changes in the dynamics of the echopattern,
      with a reduction in pixels that represent aligned and integer collagen tendon
      bundles on days 1 and 2 post-race when compared to pre-race (P<0.05). The
      echopattern of these tendons returned to baseline on day 3. This change in
      echopattern was not seen in control horses. It was concluded that short-term
      changes in the SDFT following maximal exercise could be detected using UTC.

PMID- 22658821
TI  - Non-invasive collection of exhaled breath condensate in rats: evaluation of pH,
      H2O2 and NOx in lipopolysaccharide-induced acute lung injury.
AB  - The analysis of exhaled breath condensate (EBC) offers the potential for
      identifying lung disease markers in humans and animals, but methodological issues
      and standardised procedures need to be addressed before the technique can be
      considered for use in applications to help understand the role of environmental
      pollution in respiratory diseases. The purpose of this study was to develop and
      implement a new device using a glass-chamber for collecting EBC non-invasively
      from rats in order to analyse EBC markers in lipopolysaccharide (LPS)-induced
      acute lung injury. Eighty-four adult rats were used in five different series of
      experiments to determine the source of EBC formation, intra-day and inter-day
      variability, and the influence of environmental parameters on EBC markers. The
      hypothesis that inflammation induces an oxidative stress was assessed by
      measuring pH, nitrogen oxides (NOx) and hydrogen peroxide (H(2)O(2)) in EBC. The
      results confirmed that EBC fluid was generated at the level of the respiratory
      tract. The repeatability studies of disease markers indicated higher
      concentrations of NOx and H(2)O(2) at midday compared to the morning, but there
      were no significant difference between measurements on consecutive days. EBC
      volume was influenced by both ambient temperature and humidity. Moreover, 3h
      after LPS challenge, significantly increased concentrations of both NOx and
      H(2)O(2) were observed in EBC of the LPS group compared with controls (P=0.005
      and P=0.027, respectively). These results suggested that EBC collection may be a
      valuable tool to monitor the presence of markers, such as NOx and H(2)O(2), in an
      animal model of LPS-induced acute lung injury.

PMID- 22658822
TI  - Death has a preference for birthdays-an analysis of death time series.
AB  - PURPOSE: To examine the relation between the day of death and the day of birth.
      To determine whether the "death postponement" hypothesis or the "anniversary
      reaction" hypothesis is more appropriate. METHODS: We analyzed data from the
      Swiss mortality statistics 1969-2008. Deaths below the age of 1 were excluded
      from the analysis. Time series of frequencies of deaths were based on differences
      between the day of death and the day of birth. We applied autoregressive
      integrated moving average modeling with intervention effects both in straight and
      reverse time series. RESULTS: The overall death excess on the day of birth was
      13.8%, mainly because of cardiovascular and cerebrovascular diseases (more in
      women than in men) as well as suicides and accidents (in particular, falls in
      men). Unexpectedly, we also found an excess of deaths in cancers. An (negative)
      aftereffect was found in cancers, and (positive) anticipatory effects were found
      in falls in men. CONCLUSIONS: In general, birthdays do not evoke a postponement
      mechanism but appear to end up in a lethal way more frequently than expected
      ("anniversary reaction").

PMID- 22658823
TI  - Effect of street connectivity on incidence of lower-body functional limitations
      among middle-aged African Americans.
AB  - PURPOSE: We hypothesize that lower street connectivity increases the risk of
      incident lower-body functional limitations (LBFLs) among urban African Americans
      aged 49-65 years. METHODS: This population-based cohort was interviewed in home
      visits. Five items measuring LBFL were obtained at baseline and after 3 years.
      Participants were considered to have LBFL if they reported difficulty on at least
      two of the five tasks. Census-tract street connectivity was measured as the ratio
      of the number of street intersections to the maximum possible number of
      intersections. RESULTS: Of 563 subjects with zero or one LBFL at baseline, 109
      (19.4%) experienced two or more LBFLs at the 3-year follow-up. Adjusted logistic
      regression showed that persons who lived in census tracts with the lowest
      quartile of street connectivity were 3.45 times (95% confidence interval, 1.21
      9.78) more likely to develop two or more LBFLs than those who lived in census
      tracts with the highest quartile of street connectivity independent of other
      important environmental factors. CONCLUSIONS: Areas with low street connectivity
      appear to be an independent contributor to the risk of incident LBFL in middle
      aged African Americans.

PMID- 22658824
TI  - Plasma 25-hydroxyvitamin D during pregnancy and small-for-gestational age in
      black and white infants.
AB  - PURPOSE: In a prospective prenatal cohort study, we examined associations of
      second trimester and cord plasma 25-hydroxyvitamin D (25[OH]D) with small-for
      gestational age (SGA) and the extent to which vitamin D might explain black/white
      differences in SGA. METHODS: We studied 1067 white and 236 black mother-infant
      pairs recruited from eight obstetrical offices early in pregnancy in
      Massachusetts. We analyzed 25(OH)D levels using an immunoassay and performed
      multivariable logistic models to estimate the odds of SGA by category of 25(OH)D
      level. RESULTS: Mean (SD) second trimester 25(OH)D level was 60 nmol/L (SD, 21)
      and was lower for black (46 nmol/L [SD, 22]) than white (62 nmol/L [SD, 20])
      women. Fifty-nine infants were SGA (4.5%), and more black than white infants were
      SGA (8.5% vs. 3.7%). The odds of SGA were higher with maternal 25(OH)D levels
      less than 25 versus 25 nmol/L or greater (adjusted odds ratio, 3.17; 95%
      confidence interval, 1.16-8.63). The increased odds of SGA among black versus
      white participants decreased from an odds ratio of 2.04(1.04, 4.04) to 1.68(0.82,
      3.46) after adjusting for 25(OH)D. CONCLUSIONS: Second trimester 25(OH)D levels
      less than 25 nmol/L were associated with higher odds of SGA. Our data raise the
      possibility that vitamin D status may contribute to racial disparities in SGA.

PMID- 22658825
TI  - Socioeconomic environment and recurrent coronary events after initial myocardial
      infarction.
AB  - PURPOSE: Longitudinal data linking area-level socioeconomic status (SES) to
      repeated acute coronary syndrome (ACS) events are limited. Using multiple failure
      time data, we examined the association between neighborhood SES and ACS in a
      community-based cohort of myocardial infarction (MI) survivors. METHODS:
      Consecutive patients aged 65 years or younger discharged from eight hospitals in
      central Israel after first MI in 1992-1993 were followed through 2005. Recurrent
      MI and unstable angina pectoris (UAP) leading to hospitalization were recorded.
      Neighborhood SES was assessed through a composite census-derived index developed
      by the Israel Central Bureau of Statistics. Different variance-corrected
      proportional hazards models were used to account for multiple recurrent events:
      Andersen-Gill, Wei-Lin-Weissfeld (WLW), and Prentice-Williams-Peterson. RESULTS:
      During follow-up, 531 recurrent MIs and 1584 UAP episodes occurred among 1164
      patients. Adjusting for known prognostic factors and individual SES using the
      Andersen-Gill model, higher estimated hazards were associated with poor
      neighborhood SES (hazard ratio, 1.55; 95% confidence interval [CI], 1.13-2.14 for
      recurrent MI; and hazard ratio, 1.48; 95% CI, 1.22-1.79 for UAP; in the 5th vs.
      95th percentiles). The WLW and Prentice-Williams-Peterson models yielded similar
      results. When the two outcomes were combined, the WLW-derived hazard ratio was
      1.64 (95% CI, 1.39-1.93). CONCLUSIONS: MI survivors living in a deprived
      neighborhood are at higher risk of repeated hospital admissions because of ACS.
      Secondary prevention initiatives should incorporate multilevel approaches to
      increase effectiveness and reduce geographic health disparities.

PMID- 22658826
TI  - Presynaptic neurotoxins: an expanding array of natural and modified molecules.
AB  - The process of neurotransmitter release from nerve terminals is a target for a
      wide array of presynaptic toxins produced by various species, from humble
      bacteria to arthropods to vertebrate animals. Unlike other toxins, most
      presynaptic neurotoxins do not kill cells but simply inhibit or activate synaptic
      transmission. In this review, we describe two types of presynaptic neurotoxins:
      clostridial toxins and latrotoxins, which are, respectively, the most potent
      blockers and stimulators of neurotransmitter release. These toxins have been
      instrumental in defining presynaptic functions and are now widely used in
      research and medicine. Here, we would like to analyse the diversity of these
      toxins and demonstrate how the knowledge of their structures and mechanisms of
      action can help us to design better tools for research and medical applications.
      We will look at natural and synthetic variations of these exquisite molecular
      machines, highlighting recent advances in our understanding of presynaptic toxins
      and questions that remain to be answered. If we can decipher how a given
      biomolecule is modified by nature to target different species, we will be able to
      design new variants that carry only desired characteristics to achieve specific
      therapeutic, agricultural or research goals. Indeed, a number of research groups
      have already initiated a quest to harness the power of natural toxins with the
      aim of making them more specifically targeted and safer for future research and
      medical applications.

PMID- 22658827
TI  - Reliable in vivo identification of both GABAergic and glutamatergic neurons using
      Emx1-Cre driven fluorescent reporter expression.
AB  - The development of genetically modified mice in which subpopulations of cortical
      neurons are labelled by fluorescent proteins has greatly facilitated single
      cellular imaging and electrophysiology studies in vitro and in vivo. However, the
      parallel visualization of both inhibitory and excitatory neocortical neurons
      remains problematic. We here provide an alternative approach to identify
      GABAergic neurons in the context of in vivo calcium imaging. The method relies on
      the Emx1(IREScre) recombinase driven expression of a red fluorescent protein in
      excitatory neurons and glia. We quantitatively examined the upper layers of the
      visual neocortex in vivo and found that due to pronounced neuropil staining
      Emx1(IREScre)-negative and Emx1(IREScre)-positive neurons can be reliably
      differentiated based on negative and positive contrast, respectively.
      Immunohistochemical analyses confirmed that the entire population of GABAergic
      interneurons is represented by Emx1(IREScre)-negative cells. The potential
      usefulness of the method is exemplified by calcium imaging of sensory-evoked
      responses in the primary visual cortex. We conclude that the proposed method
      extends the repertoire of strategies aimed at discriminating two major
      neocortical neuron populations in situ.

PMID- 22658828
TI  - Ca2+ signaling and gene transcription in glucose-stimulated insulinoma cells.
AB  - Glucose stimulation induces expression of the transcription factors Egr-1 and c
      Jun as well as phosphorylation of CREB and c-Jun in insulinoma cells. The
      activator protein-1 (AP-1) binding sites within the c-Jun promoter, the serum
      response elements (SREs) within the Egr-1 promoter, and cyclic AMP response
      elements (CREs) function as glucose responsive element. Glucose-induced
      transcriptional regulation was attenuated by inhibition of L-type Ca(2+)
      channels, or chelating cytoplasmic Ca(2+). It has been proposed that a rise in
      nuclear Ca(2+) is required for CREB-mediated transcription of CRE-regulated
      genes, while elevated cytoplasmic Ca(2+) levels trigger an upregulation of SRE
      containing genes. Here, we show that a rise in cytoplasmic Ca(2+) is required for
      AP-1, CRE, and SRE mediated transcription in glucose-stimulated insulinoma cells.
      Buffering Ca(2+) in the nucleus or the endoplasmic reticulum had no inhibitory
      effect upon transcription. However, overexpression of the mitochondrial protein
      Fis-1 or inhibition of the GTPase Drp-1 impaired glucose-stimulated gene
      transcription in insulinoma cells, suggesting that the mitochondria play an
      important role in regulating Ca(2+) mediated gene transcription. The
      extracellular signal-regulated protein kinase functions as an essential link
      connecting glucose stimulation, the rise in cytoplasmic Ca(2+), and enhanced
      transcription in insulinoma cells.

PMID- 22658829
TI  - Heterogeneous catalytic ozonation of ciprofloxacin in water with carbon nanotube
      supported manganese oxides as catalyst.
AB  - Carbon nanotube-supported manganese oxides (MnOx/MWCNT) were used as catalysts to
      assist ozone in degrading ciprofloxacin in water. Manganese oxides were
      successfully loaded on multi-walled carbon nanotube surfaces by simply
      impregnating the carbon nanotube with permanganate solution. The catalytic
      activities of MnOx/MWCNT in ciprofloxacin ozonation, including degradation,
      mineralization effectiveness, and antibacterial activity change, were
      investigated. The presence of MnOx/MWCNT significantly elevated the degradation
      and mineralization efficiency of ozone on ciprofloxacin. The microbiological
      assay with a reference Escherichia coli strain indicated that ozonation with
      MnOx/MWCNT results in more effective antibacterial activity inhibition of
      ciprofloxacin than that in ozonation alone. The effects of catalyst dose, initial
      ciprofloxacin concentration, and initial pH conditions on ciprofloxacin ozonation
      with MnOx/MWCNT were surveyed. Electron spin resonance trapping was applied to
      assess the role of MnOx/MWCNT in generating hydroxyl radicals (HO) during
      ozonation. Stronger 5,5-dimethyl-1-pyrroline-N-oxide-OH signals were observed in
      the ozonation with MnOx/MWCNT compared with those in ozonation alone, indicating
      that MnOx/MWCNT promoted the generation of hydroxyl radicals. The degradation of
      ciprofloxacin was studied in drinking water and wastewater process samples to
      gauge the potential effects of water background matrix on MnOx/MWCNT catalytic
      ozonation.

PMID- 22658830
TI  - Fast defluorination and removal of norfloxacin by alginate/Fe@Fe3O4 core/shell
      structured nanoparticles.
AB  - Alginate-Fe(2+)/Fe(3+) polymer coated Fe(3)O(4) magnetic nanoparticles
      (Fe(3)O(4)@ALG/Fe MNPs) with core/shell structure are prepared and used as
      heterogeneous Fenton nanocatalyst to degrade norfloxacin (NOF). The Fenton-like
      process based on Fe(3)O(4)@ALG/Fe shows much higher efficiency on NOF
      degradation. Compared with Fe(3)O(4) nanoparticle-H(2)O(2) system, NOF
      degradation in Fe(3)O(4)@AlG/Fe-H(2)O(2) system can be conducted in a wide pH
      range (pH 3.5-6.5) and independent on temperature. With 0.98 mM H(2)O(2) and 0.4
      g L(-1) Fe(3)O(4)@ALG/Fe, 100% of NOF and 90% of TOC is removed within 60 min,
      and the fluorine element in NOF molecule changes into F(-) ions within 1 min,
      indicating that NOF degradation in this Fenton-like reaction is performed through
      direct defluorination pathway. XPS analysis shows that TOC removal in reaction
      solution mainly results from the adsorption of NOF degradation intermediates on
      catalyst. Due to the paramagneticity and high saturation magnetization of
      Fe(3)O(4)@ALG/Fe, the used catalyst with adsorbed NOF intermediate is collected
      from aqueous solution by applying an external magnetic field, leading to complete
      removal of NOF from water samples. As being composed of inorganic materials and
      biopolymer, Fe(3)O(4)@ALG/Fe MNPs are robust, thermo-stable, nontoxic and
      environmentally friendly. These attractive features endow Fe(3)O(4)@ALG/Fe as a
      potent Fenton-like catalyst for fluoroquinolones degradation.

PMID- 22658832
TI  - Ultrasound IMT measurement on a multi-ethnic and multi-institutional database:
      our review and experience using four fully automated and one semi-automated
      methods.
AB  - Automated and high performance carotid intima-media thickness (IMT) measurement
      is gaining increasing importance in clinical practice to assess the
      cardiovascular risk of patients. In this paper, we compare four fully automated
      IMT measurement techniques (CALEX, CAMES, CARES and CAUDLES) and one semi
      automated technique (FOAM). We present our experience using these algorithms,
      whose lumen-intima and media-adventitia border estimation use different methods
      that can be: (a) edge-based; (b) training-based; (c) feature-based; or (d)
      directional Edge-Flow based. Our database (DB) consisted of 665 images that
      represented a multi-ethnic group and was acquired using four OEM scanners. The
      performance evaluation protocol adopted error measures, reproducibility measures,
      and Figure of Merit (FoM). FOAM showed the best performance, with an IMT bias
      equal to 0.025+/-0.225mm, and a FoM equal to 96.6%. Among the four automated
      methods, CARES showed the best results with a bias of 0.032+/-0.279mm, and a FoM
      to 95.6%, which was statistically comparable to that of FOAM performance in terms
      of accuracy and reproducibility. This is the first time that completely automated
      and user-driven techniques have been compared on a multi-ethnic dataset, acquired
      using multiple original equipment manufacturer (OEM) machines with different gain
      settings, representing normal and pathologic cases.

PMID- 22658831
TI  - Radiolaria associated with large diversity of marine alveolates.
AB  - We have isolated cells of unculturable radiolarians from marine coastal waters.
      Individual cells were subjected to single cell whole genome amplification (SCWGA)
      and gene-targeted PCR. Using this approach we recover a surprisingly large
      diversity of sequences related to the enigmatic marine alveolate groups 1 and 2
      (MALV I and MALV II) that most likely represent intracellular symbionts or
      parasites of the radiolarian cells. 18S rDNA phylogeny of the MALV sequences
      reveals 4 distinct clades of radiolarian associates here named Radiolarian
      Associated Sequences (RAS) 1-4. One clade of both phaeodarian and radiolarian
      associates and one clade of only phaeodarian associates are also identified. The
      MALV sequences cluster according to host type, i.e. sequences from associates
      identified in radiolarians, fish, copepods, ciliates or dinoflagellates are not
      intermixed but separated into distinct clades. This implies several independent
      colonizations of host lineages and links a large diversity of MALV to radiolarian
      associated species. This demonstrates that radiolarians may be an important
      reservoir for MALV, making them a key group for understanding the impact of
      intracellular symbionts on the marine ecosystem. This study shows that applying
      SCWGA on unculturable cells is a promising approach to study the vast diversity
      and interactions of intracellular eukaryote organisms.

PMID- 22658833
TI  - Surgical resection of hepatic metastases from neuroendocrine neoplasms: a
      systematic review.
AB  - BACKGROUND: Neuroendocrine tumours (NET) most commonly metastasize to the liver.
      Hepatic resection of NET hepatic metastases (NETHM) has been shown to improve
      symptomology and survival. METHODS: A systematic review of clinical studies
      before September 2010 was performed to examine the efficacy of hepatic resection
      for NETHM. As a secondary end-point, the impact of treatment on safety and
      symptomology were determined and prognostic variables were identified. The
      quality of each study was also assessed using predefined criteria incorporating 9
      characteristics. Clinical outcome was synthesized through a narrative review with
      full tabulation of results of all included studies. RESULTS: Twenty-nine included
      reported survival outcomes with a median 3-, 5- and 10-year overall survival of
      83% (range, 63-100%), 70.5% (range, 31-100%), and 42% (range, 0-100%),
      respectively. The median progression-free survival (PFS) was 21 months (range, 13
      46 months) and median 1-,3-,5- and 10-year PFS of 63% (range, 50-80 %), 32%
      (range, 24-69%), 29% (range, 6-66%) and 1% (range, 0-11%), respectively. Poor
      histologic grade, extra-hepatic disease and a macroscopically incomplete
      resection were associated with a poor prognosis. Studies reported a median rate
      of symptomatic relief from surgery in 95% of patients (range, 50-100%).
      CONCLUSION: Hepatic resection for NETHM provides symptomatic benefit and is
      associated with favourable survival outcomes although the majority of patients
      invariably develop disease progression.

PMID- 22658834
TI  - [Health care quality perceived by the patients in an urban health centre in A
      Coruna].
AB  - OBJECTIVE: The aim of this study is to explore the reliability and validity of
      the adapted questionnaire SERVPERF in primary care and to obtain a measure of
      perceived quality from the patient point of view in an urban health centre.
      METHOD: A cross-sectional descriptive study. PARTICIPANTS: One in five of all the
      patients who visited the health centre during one week in March 2010 were
      systematically selected until completing the required sample size. MAIN
      MEASUREMENTS: Personal data were collected (age, sex, nationality, marital
      status, level of studies, working status and their own perception on their health
      status). To measure the perceived quality the adapted questionnaire SERVPERF was
      used, with 22 items measured using a Likert scale (1-7), to which was added three
      open questions. RESULTS: Out of a total of 132 patients, 67% of those who
      completed the questionnaire were women. All the interscale correlations were
      positive and significant. The overall statistical value for Cronbachs-alpha was
      equal to 0.90 (95% CI: 0.87-0.93), and in all domains this value ranged from 0.71
      to 0.90. The factor analysis identified 5 factors that explained 69.8% of the
      total variance. Of the studied items, the "Individualized follow up of each
      patient by the doctor", with an average of 6.66 +/- 0.79 (95% CI: 6.53-6.79), was
      the best valued. CONCLUSIONS: The questionnaire (adapted SERVPERF) is reliable
      and valid for measuring perceived quality in primary care, and patients felt that
      the service offered is of good quality.

PMID- 22658835
TI  - Induction and characterization of endotoxin tolerance in equine peripheral blood
      mononuclear cells in vitro.
AB  - Endotoxemia is responsible for severe illness in horses. Individuals can become
      clinically unresponsive to the endotoxin molecule after an initial exposure; a
      phenomenon referred to as 'endotoxin tolerance' (ET). ET has been observed
      clinically in horses in vivo; however, cytokine expression associated with ET has
      not been investigated. The purpose of this study was to develop and validate a
      method for inducing ET in equine peripheral blood mononuclear cells (PBMC) in
      vitro, and to describe selected cytokine responses which are associated with ET.
      ET was induced by culturing cells with three concentrations of endotoxin, and
      evaluated after a second dose of endotoxin given to challenge the cells. The
      relative mRNA expression of IL-10 and IL-12 was measured by use of quantitative
      PCR. ET was induced in all cells exposed to the 2-step endotoxin challenge. The
      relative mRNA expression of IL-10 in tolerized cells was not different from
      positive control cells. In contrast, the relative mRNA expression of IL-12 in
      tolerized cells was decreased by 15-fold after the second endotoxin challenge.
      This experiment demonstrated a reliable method for the ex vivo induction of ET in
      equine PBMC. A marked suppression of IL-12 production is associated with ET.

PMID- 22658836
TI  - Effect of days in milk and milk yield on testing positive in milk antibody ELISA
      to Mycobacterium avium subsp. paratuberculosis in dairy cattle.
AB  - Milk samples are becoming more used as a diagnostic specimen for assessment of
      occurrence of antibodies to Mycobacterium avium subsp. paratuberculosis (MAP).
      This study assessed the effect of days in milk (DIM) and milk yield on testing
      positive in a commercial MAP specific milk antibody ELISA among 222,774 Danish
      Holstein cows. Results showed that odds of testing positive on 1-2 DIM were 9-27
      times higher than the rest of lactation, where the chance of testing positive
      varied less. The reason is most likely a high concentration of non-specific
      antibodies in colostrum. Consequently, samples from the first couple of DIM
      should be excluded from MAP testing until further information on their
      significance is established. Milk yield also had a significant effect on odds of
      testing positive due to its diluting effect. Inclusion of milk yield in the
      interpretation of test results could improve the diagnostic value, resulting in
      more predictable patterns corresponding to progression of infection.

PMID- 22658838
TI  - [Young hunter with high fever, migratory arthritis and macular lesions on palms
      and soles].

PMID- 22658837
TI  - Polarity and lymphocyte fate determination.
AB  - Polarity within lymphocytes has been recognized to regulate a variety of
      processes, including migration, signaling, and the execution of effector
      function. It has been recently proposed, however, that this polarized behavior
      may also serve a different purpose in lymphocytes that have not yet encountered
      their foreign antigen-to coordinate asymmetric cell division. Asymmetric division
      is an evolutionarily conserved mechanism allowing a single cell to give rise to
      two distinct daughter cells from inception. In this review, recent findings in
      polarity and asymmetric division in lymphocytes are discussed.

PMID- 22658839
TI  - Clinical outcomes using accelerated partial breast irradiation in patients with
      ductal carcinoma in situ.
AB  - BACKGROUND: Limited data exist on the use of accelerated partial breast
      irradiation (APBI) in patients with ductal carcinoma in situ (DCIS). The purpose
      of this analysis was to evaluate clinical outcomes after APBI in patients with
      DCIS. PATIENTS AND METHODS: Between December 2002 and December 2010, 99 patients
      with DCIS underwent APBI as part of their breast-conserving therapy (BCT).
      Partial breast irradiation techniques included interstitial brachytherapy,
      balloon-based brachytherapy, and 3-dimensional conformal radiotherapy (3D-CRT).
      Clinical outcomes including local recurrence, regional recurrence, disease-free
      survival (DFS), cause-specific survival, and overall survival (OS) were analyzed.
      RESULTS: Mean follow up was 3.0 years, with a mean patient age of 61.8 years. At
      5 years, the rates of local recurrence and regional recurrence were 1.4% and 0%,
      respectively. Overall survival was 94%, whereas cause-specific survival was 100%.
      No difference was noted in local control for each treatment technique. When
      comparing rates using the Eastern Cooperative Oncology Group (ECOG) E-5194 trial
      groupings, the rate of local recurrence in our cohort was 2.0% for patients with
      grade I/II disease < 2.5 cm and 0% for grade III < 1.0 cm, representing a 50% and
      100% decrease, respectively, in local recurrence compared with excision alone.
      CONCLUSIONS: Patients with DCIS treated with APBI had excellent clinical outcomes
      regardless of the APBI technique used. Until the publication of prospective phase
      III trials, these data confirm previous reports highlighting the efficacy of APBI
      in the treatment of noninvasive carcinoma of the breast.

PMID- 22658840
TI  - [Corneal imaging].
AB  - Initially developed for research purposes, several imaging techniques of the
      cornea are now available in clinical practice brought by technological advances
      that have improved resolution but have also simplified their use. In vivo
      confocal microscopy (IVCM) provides images with a resolution approaching one
      micron and permitting a histological-like in vivo imaging of the cornea. In
      parallel, Ocular Coherence Tomography (OCT) imaging techniques have been also
      developed and offers today macroscopic images of anterior segment tissues and of
      the cornea in particular. Numerous corneal diseases as well as corneal surgical
      procedures could have a benefit from these new imaging techniques of the anterior
      segment of the eye.

PMID- 22658841
TI  - Rapid cytologic diagnosis of choroidal malignant melanoma by vitreous smear.
AB  - The eye is an uncommon subject of cytopathological examination. However,
      cytopathologic examination may be required for definitive diagnosis in some
      cases, as malignant tumors of the eye may sometimes be difficult to distinguish
      clinically from benign disorders. We report a case of malignant melanoma (MM) of
      the choroid, in which vitrectomy was performed for the initial clinical diagnosis
      of vitreous hemorrhage. As the dense vitreous hemorrhage was gradually cleared
      during the vitrectomy, a choroidal mass was discovered and the vitreous fluid was
      procured for rapid cytologic diagnosis. We used a modified Shorr's stain that can
      be completed within several minutes. With this method, highly atypical,
      pleomorphic cancer cells, occasionally associated with melanin pigment granules,
      were demonstrated. These cytologic findings indicated a diagnosis of MM arising
      from the choroid. Histologic examination of the enucleated eye confirmed MM of
      epithelioid type. The advantage and indication of the rapid cytologic diagnosis
      is discussed.

PMID- 22658842
TI  - [Case report of a 45-year-old man with uveal melanoma and suspect controlateral
      choroidal naevus].
AB  - INTRODUCTION: Uveal melanoma is the most common adult primary intraoculary tumor.
      Bilateral tumor is very rare, but must not be underestimated because early
      diagnosis and care improve the survival and the visual prognosis. OBSERVATION: We
      report the case of a patient treated for a left parapapillary choroidal melanoma
      by disk of ruthenium ((106)Ru), and a follow-up every 3 months for an atypical
      choroidal large-sized controlateral naevus levelling the macular area. This right
      naevus changed in 2009 leading to suspicion of a growing melanoma. Because the
      visual acuity of the left eye was limited to 20/2000, we wanted to confirm this
      growth before beginning a treatment. But for 3 years the tumor has remained
      stable and asymptomatic, with a disease staging still negative. To this day, no
      curative treatment has been started on the right eye. DISCUSSION: In spite of
      clinical (To Find Small Ocular Melanomas (TFSOM) for example) and paraclinical
      arguments, it is sometimes difficult to differentiate a large naevus from an
      early melanoma. Evolution of the tumor often allows to confirm the diagnosis.
      However, the sole growth of a naevus is not specific of a choroidal melanoma.
      When confronted with suspicion of a small choroidal melanoma, some authors
      recommend an immediate treatment for the tumor; others prefer to confirm without
      a doubt a tumoral growth. It is necessary to weigh out the iatrogenic risks of a
      conservative treatment on the visual acuity in a monophtalm patient on one side,
      and the vital risk for the patient on the other side, which seems to be limited
      in case of small-sized melanoma with a slow evolution. CONCLUSION: A bilateral
      choroidal melanoma is rare. Systematic and repeated examinations of both eyes are
      essential. Management of these complicated cases often leads to discussion.

PMID- 22658843
TI  - Pediatric residents' knowledge of the community.
AB  - OBJECTIVE: The purpose of this study was to examine pediatric residents'
      knowledge of the communities they serve through their continuity clinics.
      DESIGN/METHODS: The community was identified for each of 6 continuity clinics at
      an urban children's hospital by geocoding patient addresses using GIS software (1
      hospital-based [n = 36], 1 primary care track site [n = 10], and 4 community
      clinics [n = 12]). We assessed resident and attending knowledge with a survey
      examining 7 content areas with basic questions about these communities. The
      survey answers were compared with publicly available community data. RESULTS: A
      total of 37 of 57 eligible residents (65%) and 21 of their 23 attendings (91%)
      completed the survey. The residents achieved an overall mean score of 28.9%
      correct (SD 9.2) and attendings scored 42.6% (SD 19.7). Scores were significantly
      greater for community-based attendings overall (P < .002) and for community-based
      residents only in the questions of schools (P < 0.001). However, community-based
      residents had poorer scores in the demographics/economics content area (P <
      0.001). Scores were not correlated with year of residency. CONCLUSIONS: Our
      pediatric professional organizations have recognized the importance of training
      residents in community pediatrics. This study is the first to describe resident
      community knowledge and to demonstrate that this knowledge is generally poor,
      with specific gaps in the content areas of schools, daycares, and health care
      access. There are differences in areas of knowledge between those working in
      hospital versus community clinics, suggesting this is an area for further
      investigation.

PMID- 22658844
TI  - Prescribing for athletes and plastic surgery.

PMID- 22658845
TI  - Contoured in-shoe foot orthoses increase mid-foot plantar contact area when
      compared with a flat insert during cycling.
AB  - OBJECTIVES: To determine the effect of contouring of an in-shoe foot orthosis on
      plantar contact area and surface pressure, as well as perceived comfort and
      support at the foot-orthosis interface during stationary cycling. DESIGN: A
      randomised, repeated measures control study. METHODS: Twelve cyclists performed
      steady-state seated cycling at a cadence of 90 rpm using a contoured orthosis and
      a flat insert of similar hardness. Contact area (CA) and plantar mean pressure
      (PP) were measured using the PEDAR(r) system, determined for seven discrete
      plantar regions and represented as the percentage of the total CA and PP
      respectively (CA% and PP%). Perceived comfort and support were rated using a
      visual analogue scale (VAS). RESULTS: The contoured orthosis produced a
      significantly greater CA% at the medial midfoot (p=0.001) and lateral midfoot
      (p=0.009) with a standardised mean difference (SMD) of 1.3 and 0.9 respectively.
      The contoured orthosis also produced a significantly greater PP% at the hallux
      (p=0.003) compared to the flat insert with a SMD of 1.1. There was a small non
      significant effect (SMD<0.4) for the perceived comfort measures between
      conditions, but perceived support was significantly greater at the arch (p=0.000)
      and heel (p=0.013) with the contoured orthoses (SMD of 1.5 and 0.9,
      respectively). CONCLUSIONS: Contoured orthoses influenced the plantar surface of
      the foot by increasing contact area as well as a perception of greater support at
      the midfoot while increasing relative pressure through the hallux when compared
      to a flat insert during stationary cycling. No difference in perceived comfort
      was noted.

PMID- 22658846
TI  - Contrast enhanced ultrasound: Should it play a role in immediate evaluation of
      liver tumors following thermal ablation?
AB  - PURPOSE: To compare the accuracy of immediate CEUS with results of 24-h CEUS and
      MDCT in early evaluation of liver tumors following thermal ablation, using the
      combined results of a 3 month follow-up MDCT and CEUS as a reference standard.
      SUBJECTS AND METHODS: From our database, we selected patients who underwent a
      thermal ablation immediately followed by CEUS (within 5-10min) between February
      2009 and February 2011. There were 92 patients (median age 73 years), two of whom
      had repeat ablation during the study period for a total of 94 tumors. Sixty
      tumors were treated with radiofrequency and 34 with microwave ablation. All
      patients underwent CEUS and CT examinations at 24h. For patients with more than
      one treated tumor in the same session, the lesion imaged post-procedural and at
      24-h with CEUS in all vascular phases was selected. All measurements of the
      necrotic zone, as an avascular zone, were performed during the portal-venous
      phase. Immediate post-procedural CEUS and 24h CEUS and MDCT were blindly reviewed
      by two radiologists. One radiologist blindly reviewed the follow-up imaging. The
      mean diameters of the necrotic zone at post-procedural CEUS, and CEUS and MDCT at
      24h were compared and diagnostic accuracy to detect residual tumor calculated for
      each index tests compared to 3-months follow-up imaging. RESULTS: The mean
      diameter of the necrotic zone was: 29+/-9mm at post-procedural CEUS, 34+/-10mm at
      24h CEUS and 35+/-11mm at 24h MDCT. Mean diameter of the necrotic zone was
      significantly smaller at post-procedural CEUS compared to either CEUS or MDCT at
      24h (p<0.001 for all). With a 95% confidence interval, the sensitivity was 25%
      (11-47%) for immediate CEUS, 20% (8-42%) for CEUS at 24-h, and 40% (22-61%) for
      CT at 24-h. Specificity was 96% (89-99%) for immediate CEUS, 97% (91-99%) for
      CEUS at 24-h, and 97% (91-99%) for CT at 24-h. CONCLUSIONS: Diagnostic accuracy
      of post-procedural CEUS in early evaluation of liver tumors following thermal
      ablation is comparable to both CEUS and MDCT performed at 24h. Therefore, post
      procedural CEUS can be used to detect and retreat residual viable tissue in the
      same ablation session.

PMID- 22658847
TI  - CT presentations of colorectal cancer with chronic schistosomiasis: A comparative
      study with pathological findings.
AB  - OBJECTIVE: To clarify pathological basis of computed tomography (CT)
      presentations of colorectal cancer (CRC) with schistosomiasis for the purpose of
      improving the accuracy of CT diagnosis and differential diagnosis of the
      condition. MATERIALS AND METHODS: 130 patients (87 male and 43 female; age range
      49-86 years, mean 71.1) were selected whose diagnoses were pathologically
      confirmed as CRC with schistosomiasis. All the patients underwent abdominal plain
      CT and contrast enhanced scanning. The location, morphology, size, calcification
      features and enhancement modalities (patterns) were evaluated and compared with
      the pathological findings by two radiologists in a blind way. RESULTS: CT showed
      that in 130 patients, the tumors occurred in the large intestine, among which 109
      (83.9%) were solitary and 21 (16.1%) were multifocal. The intestinal wall was
      irregularly thickened in 123 patients, with soft tissue masses in 7 patients.
      Linear, spotty and small patchy calcifications were seen in 104 (80.0%) patients,
      with unclear margins in 96 patients. The tumors were markedly unevenly enhanced
      in 92 patients. Pathological examination revealed adenocarcinoma in 114 patients
      and in 104 patients, calcified Shistosoma japonicum (S. japonicum) ova inside the
      tumors, 15 patients were mucinous adenocarcinoma, and one patient was that of
      adenosquamous carcinoma. CONCLUSION: Irregular thickening of the intestinal wall,
      soft tissue masses, multiple S. japonicum ova calcifications inside the tumor
      with obscured margins and multiple intestinal masses in some patients are
      important CT features of CRC with schistosomiasis.

PMID- 22658848
TI  - Intraoperative neurophysiological monitoring in acute paralysis from spinal cord
      epidural abscess.

PMID- 22658849
TI  - Cryptic insertion of BCL2 gene into immunoglobulin heavy locus in follicular
      lymphoma with t(6;9)(p23;p13).

PMID- 22658850
TI  - Serum double monoclonal components and hematological malignancies: only a casual
      association? Review of 34 cases.
AB  - A double monoclonal component (MC) detected in the serum and/or urine represents
      a very rare occurrence (2-6% of monoclonal gammopathies). In this study, we
      report 34 patients with double serum MCs, focusing on the associated diseases.
      The diagnosis was made using high-resolution serum protein electrophoresis and
      immunofixation. Of the 1214 patients with monoclonal gammopathies, 49 had a
      double MC but only 34 (2.8%) were included in our study. A double MC was
      associated with hematological malignancies in 20/34 cases. Based on our
      experience, a double MC is more often associated with other diseases, especially
      an oncohematological one.

PMID- 22658851
TI  - Integrin-linked kinase is dispensable for multiple myeloma cell survival.
AB  - We investigated the utility of integrin-linked kinase (ILK) as a target for
      therapeutic intervention in multiple myeloma (MM). ILK (over-)expression was
      assessed in primary samples and MM cell lines, and the molecular and
      physiological consequences of siRNA-mediated ILK ablation were compared to
      treatment with the small molecule inhibitor QLT0267. Whereas ILK expression was
      ubiquitous, overexpression was only rarely observed in patient biopsies. ILK
      knockdown had no effect on the viability or survival pathway activity pattern of
      MM cells. Conversely, QLT0267 induced cell death in MM cell lines and most
      primary tumor samples via the intrinsic apoptotic pathway. Although this effect
      was largely tumor cell-specific it is unlikely to have been mediated via ILK. We
      conclude that ILK does not play a prominent role in the promotion or sustenance
      of established MM.

PMID- 22658852
TI  - Role of mast cell chymase and tryptase in the progression of atherosclerosis:
      study in 44 autopsied cases.
AB  - The aim of this study was to describe the role of mast cell chymase and tryptase
      in the progression of atherosclerosis. Forty-four sections of aortas were
      obtained from autopsies. We assessed the macroscopic degree of atherosclerosis,
      microscopic intensity of lipid deposition in the tunica intima, percentage of
      collagen in the tunica intima, and density of immunostained mast cells. There was
      no significant difference between the density of mast cell tryptase and chymase
      concerning ethnicity, sex, cause of death, or degree of atherosclerosis. The
      density of mast cell chymase was significantly higher in the nonelderly group.
      The percentage of collagen was significantly higher in elderly patients. There
      was a positive and significant correlation between the degree of macroscopic
      atherosclerosis and lipidosis, the density of mast cell chymase and the
      percentage of collagen, the density of mast cell tryptase and the percentage of
      collagen, and lipidosis and the density of mast cell tryptase. The degree of
      macroscopic lesion of atherosclerosis increased proportionally with the increase
      in the density of mast cell chymase and tryptase and in the intensity of lipid
      deposition and with the percentage of collagen in the atherosclerotic plaques.
      Thus, mast cells may play a crucial role in aggravating atherosclerotic lesions.

PMID- 22658853
TI  - Cystic lung lesions in Sjogren syndrome: analysis of lymphocyte subsets in tissue
      with clinico-radiologic-pathologic correlation.
AB  - Pulmonary complications associated with Sjogren syndrome (SS) have attracted
      attention in recent years. Sjogren syndrome has been associated with small cyst
      formation in salivary glands, thymus, and lungs and has been recently brought to
      the forefront by radiologists due to high-resolution techniques. However,
      pathologists are less aware of this finding unless clinico-radiologic-pathologic
      correlation is sought. Formation of large bullae in SS is a rare complication
      with potential for confusion with other diseases. Here, we present the clinical,
      radiologic, and pathologic findings in 3 patients with SS associated with
      multiple pulmonary cystic lesions. All 3 patients had a variable mixed
      restrictive and obstructive component of the disease. There was good correlation
      with the pulmonary function tests (PFTs), high-resolution computed tomographic
      scan, and morphology with regard to the restrictive component. The small cysts
      appear to correlate with the extent of obstructive changes on the PFTs. However,
      the large bullae do not, implying noncommunication with the conducting airways.
      This noncorrelation between the PFTs and extent of bullous disease with
      predominant involvement of lower lobes in SS enables distinction from bullous
      emphysema. The mechanism of bulla formation in SS appears to be different from
      bullous emphysema. A check valve mechanism has been proposed previously in SS,
      which does not explain cyst formation in the thymus. Alternately, inflammation
      may play a role with the key suspects being CD4 T-helper cells and perhaps NK
      cells. This is the first report of a clinico-radiologic-pathologic correlation
      with analysis of lymphocyte subsets.

PMID- 22658854
TI  - Extracolonic gastrointestinal tract morphologic findings in a case of
      pseudomembranous collagenous colitis.
AB  - "Pseudomembranous collagenous colitis" is a morphologic variant of collagenous
      colitis in which active inflammation with pseudomembrane formation is prominent
      and which has been associated with infectious, toxic, and ischemic etiologies.
      However, extracolonic morphologic findings in patients with pseudomembranous
      collagenous colitis have not been previously described. Here, we present a case
      of a patient with pseudomembranous collagenous colitis with abnormal extracolonic
      findings. These include gastric antral mucosa with histologic features
      reminiscent of ischemic injury and reactive gastropathy with intraepithelial
      lymphocytosis and partial villous atrophy in the duodenal and ileal biopsies. The
      findings in the small intestinal biopsies resemble those seen in enteric mucosa
      in patients with conventional collagenous colitis. Our pathologic findings as
      well as the clinical course of the patient further emphasize the clinical and
      histologic similarities shared by pseudomembranous collagenous colitis and
      conventional collagenous colitis.

PMID- 22658855
TI  - Bone marrow mesenchymal stem cells ameliorate hepatic ischemia/reperfusion
      injuries via inactivation of the MEK/ERK signaling pathway in rats.
AB  - BACKGROUND: Primary graft dysfunction or nonfunction after liver transplantation,
      which is usually caused by ischemia/reperfusion injury (IRI), is a serious
      clinical problem. Although bone marrow mesenchymal stem cells (MSCs) have shown
      great potential in cell therapy for IRI in several organs, the mechanism(s) by
      which MSCs offer protection is unclear. METHODS: In the present study, we
      injected MSCs systemically via the tail vein in the rat model of 70% hepatic IRI
      and measured the biochemical and pathologic alterations to evaluate the
      therapeutic effect of MSC transplantation. Concurrently, H(2)O(2) was used in
      vitro to mimic oxidative injury and to induce apoptosis in the human normal liver
      cell line LO2 to evaluate the protective effects of mesenchymal stem cell
      conditioned medium (MSC-CM) on LO2 cells. RESULTS: The systemic infusion of MSCs
      led to a significant prevention of liver enzyme release and an improvement in the
      histology of the acutely injured liver. In vitro assays demonstrated that MSC-CM
      promoted hepatocyte proliferation and had a direct inhibitory effect on
      hepatocyte apoptosis induced by H(2)O(2). In addition, we demonstrated that the
      prevention of MEK/ERK pathway activation played a pivotal role in the protection.
      CONCLUSIONS: These data suggest that MSC may represent a potential therapeutic
      strategy to alleviate hepatic ischemia/reperfusion injuries after liver
      transplantation via inactivation of the MEK/ERK signaling pathway.

PMID- 22658856
TI  - Renal dysfunction by BK virus infection is correlated with activated T cell level
      in renal transplantation.
AB  - BACKGROUND: BK virus (BKV) is known to be associated with nephropathy. Here, we
      investigated the relationships between BKV levels, T-cell activation, and kidney
      function in kidney transplant recipients. MATERIALS AND METHODS: In renal
      transplant patients and controls, urine BKV levels were detected by quantitative
      real-time PCR, and the percentage of activated T lymphocytes in blood was
      determined by flow cytometry. The correlations between viral load, activated T
      cell percentage, and renal function were determined. RESULTS: Urine BKV viral
      loads and the activated T cell percentage were significantly elevated in
      transplant recipients. Correlational analysis indicated that transplant
      recipients that had BKV levels of more than 10(6) copies/mL and an activated T
      lymphocyte percentage of less than 20% were likely to have poor renal function.
      CONCLUSIONS: Urine BKV levels and the percentage of activated T lymphocytes can
      be used as clinical indices to optimize the dosage of immunosuppressive drugs.

PMID- 22658857
TI  - Immunization of cattle with Ra86 impedes Rhipicephalus appendiculatus nymphal-to
      adult molting.
AB  - Commercial vaccines based on the tick gut protein Bm86 have been successful in
      controlling the one-host tick Rhipicephalus (Boophilus) microplus and provide
      heterologous protection against certain other non-target ixodid tick species.
      This cross protection, however, does not extend to the three-host tick R.
      appendiculatus, the vector of the protozoan parasite Theileria parva. When
      transmitted to cattle, T. parva causes the often fatal disease East Coast fever.
      Here, we used insect cell-expressed recombinant versions of the R. appendiculatus
      homologs of Bm86, named Ra86, to vaccinate cattle. We measured multiple fitness
      characteristics for ticks that were fed on cattle Ra86-vaccinated or
      unvaccinated. The Ra86 vaccination of cattle significantly decreased the molting
      success of nymphal ticks to the adult stage. Modeling simulations based on our
      empirical data suggest that repeated vaccinations using Ra86 could reduce tick
      populations over successive generations. Vaccination with Ra86 could thus form a
      component of integrated control strategies for R. appendiculatus leading to a
      reduction in use of environmentally damaging acaricides.

PMID- 22658858
TI  - Comparison of Actical and activPAL measures of sedentary behaviour in preschool
      children.
AB  - OBJECTIVES: The purpose of this study was to examine the convergent validity of
      the Actical and activPAL to measure sedentary behaviour (SB) and non-SB in
      preschoolers in a free-living environment. DESIGN: A convenience sample of 49
      preschoolers (22 boys; 4.0 +/- 0.5 years) from six early childhood centres in
      Auckland, New Zealand were included in data analysis. METHODS: Participants wore
      a hip-mounted Actical and a thigh-mounted activPAL accelerometer simultaneously
      during centre attendance for one day and data were collected in 15s epochs. Bland
      Altman tests were used to assess differences in group mean minutes and percentage
      of time in (non-)SB between both monitors. Agreement between binary coded (SB vs.
      non-SB) 15s-by-15s Actical and activPAL data was evaluated by calculating
      percentage agreement and kappa statistic. RESULTS: The monitors were worn on
      average for 294.8 +/- 46.3 min resulting in a total of 57,780 15s epochs. Bland
      Altman tests suggested a small group mean difference in (non-)SB (1.3 min; 0.1%)
      and a wide prediction interval (121.3 min; 39.2%). No obvious systematic bias was
      observed in the Bland-Altman plot. Percentage agreement between the 15s-by-15s
      Actical and activPAL data of all participants was 73.0% (inter-child range: 36.8
      93.8%). The kappa statistic showed moderate agreement with a value of 0.46 (95%
      CI: 0.45-0.47). CONCLUSIONS: Although the group mean estimate of (non-)SB was
      similar between the Actical and activPAL, the output of both monitors cannot be
      considered convergent as meaningful random disagreement was found between both
      monitors.

PMID- 22658859
TI  - Exploring the heterogeneous interfaces in organic or ruthenium dye-sensitized
      liquid- and solid-state solar cells.
AB  - The interfacial properties were systematically investigated using an organic
      sensitizer (3-(5'-{4-[(4-tert-butyl-phenyl)-p-tolyl-amino]-phenyl}
      [2,2']bithiophenyl-5-yl)-2-cyano-acrylic acid (D)) and inorganic sensitizer
      (bis(tetrabutylammonium) cis-bis(thiocyanato)bis(2,2'-bipyridine-4,4'
      dicarboxylato) ruthenium(II) (N719)) in a liquid-state and a solid-state dye
      sensitized solar cell (DSC). For liquid-DSCs, the faster charge recombination for
      the surface of D-sensitized TiO2 resulted in shorter diffusion length (LD) of
      ~3.9 MUm than that of N719 (~7.5 MUm), limiting the solar cell performance at
      thicker films used in liquid-DSCs. On the other hand, for solid-DSCs using thin
      TiO2 films (~ 2 MUm), D-sensitized device outperforms the N719-sensitized device
      in an identical fabrication condition, mainly due to less perfect wetting ability
      of solid hole conductor into the porous TiO2 network, inducing the dye monolayer
      act as an insulation layer, while liquid electrolyte is able to fully wet the
      surface of TiO2. Such insulation effect was attributed to the fact that the
      significant increase in recombination resistance (from 865 to 4,400 Omega/cm(2))
      but shorter electron lifetime (from 10.8 to 0.8 ms) when compared to liquid-DSCs.
      Higher recombination resistance for solid-DSCs induced the electron transport
      limited situation, showing poor performance of N719-sensitized device which has
      shorter electron transport time and similar LD (2.9 MUm) with D-sensitized device
      (3.0 MUm). 

PMID- 22658860
TI  - Detecting broken-wire flaws at multiple locations in the same wire of
      prestressing strands using guided waves.
AB  - Broken wires often occur at multiple locations in the same wire of a strand due
      to the recovery length, which is defined as the length of the wire taking up its
      full share of the axial load from the break point. The detection of broken-wire
      flaws at multiple locations along the same wire is investigated using guided
      waves below 400kHz. Herein, a sample with three broken-wire flaws in the same
      wire is analyzed using magnetostrictive guided waves. Our data show that three
      flaws are found using the low-frequency guided waves (50kHz) but only one flaw is
      found using the high-frequency guided waves (320kHz). By analyzing the reflection
      and transmission coefficients at the three different flaws, we observe that the
      energy exchange decreases as the frequency increases along the same propagating
      distance. Hence, the recovery length for elastic waves, the length of the wire
      taking up its full share of elastic-wave energy from the break point, is
      observed. The recovery length for elastic waves in prestressing strands increases
      with the frequency. To detect prestressing strands using magnetostrictive guided
      waves, several one-broken-wire flaws at different locations can be distinguished
      from in different wires or the same wire by employing both low-frequency waves
      and high-frequency waves. Nevertheless, we cannot identify in which wire the
      flaws are located because the magnetostrictive sensor analyzes the whole strand.

PMID- 22658861
TI  - Numerical modeling of thermoelastic generation of ultrasound by laser irradiation
      in the coupled thermoelasticity.
AB  - Laser-generation of ultrasound is investigated in the coupled dynamical
      thermoelasticity in the presented paper. The coupled heat conduction and wave
      equations are solved using finite differences. It is shown that the application
      of staggered grids in combination with explicit integration of the wave equation
      facilitates the decoupling of the solution and enables the application of a
      combination of implicit and explicit numerical integration techniques. The
      presented solution is applied to model the generation of ultrasound by a laser
      source in isotropic and transversely isotropic materials. The influence of the
      coupling of the generalized thermoelasticity is investigated and it will be
      shown, that for ultra high frequency waves (i.e. 100GHz) generated by laser
      pulses with duration in the picosecond range, the thermal feedback becomes
      considerable leading to a strong attenuation of the longitudinal bulk wave.
      Moreover, the coupling leads to dispersion influencing the wave velocities at low
      frequencies. The numerical simulations are compared to theoretical results
      available in the literature. Wave fields generated by a line focused laser source
      are presented by the numerical model for isotropic and for transversely isotropic
      materials.

PMID- 22658862
TI  - Discovery of pyrazole carboxylic acids as potent inhibitors of rat long chain L-2
      hydroxy acid oxidase.
AB  - Long chain L-2-hydroxy acid oxidase 2 (Hao2) is a peroxisomal enzyme expressed in
      the kidney and the liver. Hao2 was identified as a candidate gene for blood
      pressure (BP) quantitative trait locus (QTL) but the identity of its
      physiological substrate and its role in vivo remains largely unknown. To define a
      pharmacological role of this gene product, we report the development of selective
      inhibitors of Hao2. We identified pyrazole carboxylic acid hits 1 and 2 from
      screening of a compound library. Lead optimization of these hits led to the
      discovery of 15-XV and 15-XXXII as potent and selective inhibitors of rat Hao2.
      This report details the structure activity relationship of the pyrazole
      carboxylic acids as specific inhibitors of Hao2.

PMID- 22658863
TI  - A novel franchetine type norditerpenoid isolated from the roots of Aconitum
      carmichaeli Debx. with potential analgesic activity and less toxicity.
AB  - Further investigation on the phytochemistry of the plant Aconitum carmichaeli
      Debx. led to isolate a new franchetine type C(19)-diterpenoid alkaloid, guiwuline
      1. Its structure was established on the basis of the spectroscopic data (1D and
      2D NMR, HRESIMS, UV, IR). In mouse hot-plate test and acute toxicity assay,
      compound 1 exhibited potential analgesic activity (ED(50), 15 mg/kg) and showed
      little toxicity to mice (LD(50), 500 mg/kg). The results indicate that compound 1
      may be used as a lead molecule to develop novel analgesic agents.

PMID- 22658864
TI  - Synthesis and evaluation of novel podophyllotoxin analogs.
AB  - Because prior studies have shown inconsistency between structure-activity
      relationships for podophyllotoxin derivatives as topoisomerase II inhibitors and
      cytotoxic agents, eight novel podophyllotoxin analogs were synthesized to further
      explore the effects of structural variations on both A and D rings on activity.
      The new compounds contain a 4,5-dimethoxy substituted A ring and opened D-ring
      variants and were prepared by appropriate functional and stereochemical
      operations at the methylenedioxy group, C7, C8, and C8'. Four compounds (15, 18,
      21 and 22) demonstrated noticeable inhibitory activity against A549, DU145, KB
      and KBvin tumor cells, and the most active compound 18 showed IC(50) values less
      than 10 MUg/mL.

PMID- 22658866
TI  - [Compliance among adolescents with a chronic illness: review].
AB  - The continual progress in medicine has increased patient life expectation.
      However, treatments for chronic diseases are often consequential. This leads to
      problems of patient compliance, most particularly in teenage patients. Depression
      is frequently observed in persons affected by a chronic illness. These diseases
      can cause despair, which contributes to the risk of suicide. This article
      investigates the various notional and explanatory approaches to compliance. The
      literature review was based on the CAIRN, Medline, and EBSCOhost databases. The
      period investigated extended from 1999 to 2009. The keywords used were "adhesion
      therapeutique", "observance", "compliance", "adolescence", "chronic illness", and
      "depression". Three axes stand out from this review: (1) the theoretical
      definition of compliance, (2) the frequency of depressive disorders among
      adolescents affected by a chronic illness, (3) the different ways to interpret
      compliance. We introduce and discuss the contents of each of these axes and
      discuss how they could orient research on the compliance of adolescents with a
      chronic illness.

PMID- 22658865
TI  - [Children living with life-limiting conditions: practices and needs in France].
AB  - INTRODUCTION: In France, nearly 600 children, aged 1-14 years, die from chronic
      diseases every year. A law passed the 22nd of April 2005 provides the legal
      framework for end-of-life situations. However, is this law and the position
      adopted by the scientific pediatric societies known and applied by pediatricians
      dealing with these children at the end of life? Our objective was to describe the
      current practices and needs, an essential preliminary assessment for the
      development of shared concepts among pediatricians. METHOD: A long-term study
      based on a qualitative and semi-quantitative questionnaire was conducted on
      pediatricians throughout the French academic hospitals via interviews. RESULTS: A
      25.2% response rate was obtained. All of the pediatric disciplines were affected
      by end-of-life care for children. Decisions for limitation of treatment conformed
      to a collegial process in 88.9%; 48.1% of the pediatricians expressed the need
      for dedicated beds for these children. The Leonetti law appeared to be diversely
      known and appreciated: 19.6% declared no or poor knowledge of this law, 23.5%
      were neutral in their response, 15.7% considered its significant progress, and
      41.2% criticized its insufficiencies. However, for most of the doctors
      interviewed, this law supplied a legal framework, but some doctors emphasized the
      challenges in applying it to pediatrics: vagueness of the law regarding the
      parents and the desires of the minor child and insufficiency in developing
      pediatric palliative care. Above all, some ignorance or confusion in the terms
      used was notable. CONCLUSION: Our survey, emphasizing the difficulties
      encountered by pediatricians dealing with dying children and their families,
      emphasizes the need for concepts shared by the entire profession; this reflection
      could define the terms used in the debate.

PMID- 22658867
TI  - Thirty-nine cases of intracranial hemangiopericytoma and anaplastic
      hemangiopericytoma: a retrospective review of MRI features and pathological
      findings.
AB  - OBJECTIVE: To retrospectively review the imaging features of surgically and
      pathologically confirmed intracranial hemangiopericytoma and anaplastic
      hemangiopericytoma. METHODS: Thirty-nine cases of surgically and pathologically
      confirmed hemangiopericytoma and anaplastic hemangiopericytoma were analyzed
      retrospectively. The MRI features were compared with pathological findings in all
      cases. RESULTS: Of the 39 cases, 21 were anaplastic hemangiopericytoma (WHO grade
      III) and the remaining cases were hemangiopericytoma (WHO grade II); all lesions
      were solitary. MRI of anaplastic hemangiopericytoma showed that 20 cases were
      lobulated, and nine grew cross-leaf. The lesions showed mixed iso-high-low signal
      (n=20) or iso-signal (n=1) on plain T1WI, and mixed high-low signal (n=20) or iso
      signal (n=1) on plain T2WI. After contrast injection, marked heterogeneous
      enhancement was seen in 19 cases. Significant necrosis and cystic changes were
      seen in 16 cases, and the "dural tail sign" was found in two cases. Ten cases had
      bony destruction, and 16 showed significant peritumoral edema. In 18 cases of
      hemangiopericytoma, nine were oval-shaped and three grew cross-leaf. The lesions
      showed mixed iso-low signal (n=10) or iso-signal (n=8) on plain T1WI, and mixed
      iso-high signal (n=10) or iso-signal (n=8) on plain T2WI. After contrast
      injection, significant uniform enhancement was seen in 10 cases. Significant
      necrosis and cystic changes were seen in seven cases, and "dural tail sign" was
      seen in six cases. Two cases had bony destruction. No case showed significant
      peritumoral edema. Pathological immunohistochemical Ki67 staining showed a
      concentration of ~18.4% positive cells in anaplastic hemangiopericytoma, whereas
      in hemangiopericytoma it was 7.12%. CONCLUSION: Imaging findings of intracranial
      anaplastic hemangiopericytoma had more pronounced lobulation, cross-leaf growth
      tendency, more and easier bleeding, more necrosis, more cystic changes giving
      rise to heterogeneous signals, rarer frequency of the "dural tail sign", more
      damage near the skull, and more significant peritumoral edema than
      hemangiopericytoma. These features may help differentiate these two types of
      malignancy.

PMID- 22658868
TI  - Diffusion-weighted MR imaging of the breast: advantages and pitfalls.
AB  - The aim of this paper is to review all clinical applications of diffusion
      weighted MR imaging (DWI) for breast pathology. The challenge of DWI is to obtain
      the best compromise between lesion detection and characterization. Technical
      factors affecting lesion characterization and detection are detailed including
      the effect of contrast administration, the choice of number of b and of b(max),
      the variation of diagnostic performance according to the type and the size of
      lesion studied.

PMID- 22658869
TI  - Refuse derived soluble bio-organics enhancing tomato plant growth and
      productivity.
AB  - Municipal bio-refuse (CVD), containing kitchen wastes, home gardening residues
      and public park trimmings, was treated with alkali to yield a soluble bio-organic
      fraction (SBO) and an insoluble residue. These materials were characterized using
      elemental analysis, potentiometric titration, and 13C NMR spectroscopy, and then
      applied as organic fertilizers to soil for tomato greenhouse cultivation. Their
      performance was compared with a commercial product obtained from animal residues.
      Plant growth, fruit yield and quality, and soil and leaf chemical composition
      were the selected performance indicators. The SBO exhibited the best performance
      by enhancing leaf chlorophyll content, improving plant growth and fruit ripening
      rate and yield. No product performance-chemical composition relationship could be
      assessed. Solubility could be one reason for the superior performance of SBO as a
      tomato growth promoter. The enhancement of leaf chlorophyll content is discussed
      to identify a possible link with the SBO photosensitizing properties that have
      been demonstrated in other work, and thus with photosynthetic performance.

PMID- 22658870
TI  - Vermicomposting toilets, an alternative to latrine style microbial composting
      toilets, prove far superior in mass reduction, pathogen destruction, compost
      quality, and operational cost.
AB  - Composting toilets aim to recycle excrement into safe, stable humus. Preceding
      this, low costs, low risks, and mass reduction should be ensured. Source
      separating vermicomposting toilets (SSVCs) outperformed mixed latrine microbial
      composting toilets (MLMCs) in all categories. MLMCs: incurred ten times greater
      operational costs; created 10x more operator exposure; employed no proven
      pathogen reduction mechanism since solid end-products averaged 71,000+/
      230,000CFU/g (fecal-origin) Escherichia coli and 24+/-5% total solids,
      consistently failed NSF/ANSI Standard 41; failed to reduce volatile solids
      compared to raw fecal matter; increased total contaminated dry mass by 274%, and
      produced alkaline end-product (8.0+/-0.7) high in toxic free ammonia (Solvita(r)
      2.6+/-1.5). SSVCs have low maintenance costs and risks; adequate worm density for
      pathogen destruction (0.03+/-0.04g-worm/g-material); reduced E. coli 200+/
      244CFU/g in neutral (7.4+/-0.3), stable (60+/-10% volatile solids), and mature
      (4+/-0 Solvita(r) NH(3)) end-product.

PMID- 22658871
TI  - A novel form of antihelix deformity.
AB  - This report describes a novel form of congenital antihelix deformity. A 2-month
      old female presented with an antihelix deformity. Her inferior crus of the
      antihelix had the third crus, which was smoothly divided from the inferior crus,
      orienting forward. This type of deformity is not included in the current
      classification of a third crus deformity; therefore, this is the first report of
      a novel type of deformity.

PMID- 22658872
TI  - Murine typhus in central Greece: epidemiological, clinical, laboratory, and
      therapeutic-response features of 90 cases.
AB  - OBJECTIVES: To document and evaluate the clinico-epidemiological profile of
      murine typhus during the re-emergence of the disease in a previously endemic
      focus in central Greece. METHODS: This was a 5-year, hospital-based,
      observational study, in which 90 adult patients with murine typhus were
      prospectively identified and studied. RESULTS: Most cases of the disease occurred
      in rural (52%) and semi-urban (34%) settings, with a seasonal frequency peak
      during the late summer. The triad of fever, headache, and rash was present in 64%
      of the patients within 2 days of hospital admission. Normal white blood cell
      counts (63%), thrombocytopenia (81%), and a high erythrocyte sedimentation rate
      (93%) were the main hematological findings upon presentation. Elevated
      aminotransferases (>84%), hypoalbuminemia (81%), and hyponatremia (36%) were
      prominent biochemical abnormalities. Pulmonary, neurological, and renal
      complications were noted in 26% of the patients and subsided after specific
      treatment. The duration of fever was shorter in patients treated with doxycycline
      (median 3 days) compared to ofloxacin (p=0.001) or doxycycline plus ofloxacin
      (p=0.009). CONCLUSIONS: Murine typhus has the potential to cause significant
      morbidity. Awareness of the disease in endemic areas, early recognition of its
      clinical and laboratory features, and prompt administration of effective
      treatment are key factors to prevent potentially severe complications.

PMID- 22658873
TI  - Analysis of variables and interactions among variables associated with a
      sustained virological response to pegylated interferon alfa-2a plus ribavirin in
      hepatitis C virus genotype 3-infected patients.
AB  - BACKGROUND: The recommended standard therapeutic regimen for chronic hepatitis
      patients with hepatitis C virus (HCV) genotype 3 is pegylated interferon plus
      ribavirin for 24 weeks. The aim of the present study was to evaluate treatment
      efficacy and variables predictive of treatment success, interactions among
      variables contributing to a response to therapy, and the utility of the rapid
      virological response (RVR; week 4 virological response) to predict treatment
      outcomes in HCV genotype 3-infected patients in routine clinical practice.
      METHODS: We prospectively studied baseline and during-treatment factors
      associated with a sustained virological response (SVR) in HCV genotype 3-infected
      patients who received pegylated interferon alfa-2a (PEG-IFN alpha2a) 180 MUg/week
      plus ribavirin 800 mg daily for 24 weeks and who were followed for 24 weeks after
      the completion of treatment. RESULTS: Four hundred and twenty-six treated
      patients were included in the analysis; 320 (75.1%) showed an SVR. The following
      factors were assessed for their ability to predict SVR by means of univariable
      and multivariable logistic regression analysis: patient age, sex, pre-treatment
      viral load, pre-treatment alanine aminotransferase (ALT), body mass index (BMI),
      and RVR. Four factors - age, pre-treatment viral load, pre-treatment ALT, and RVR
      - were statistically significant predictors of SVR (p<0.05) in the univariable
      analysis. Factors showing a significant association with SVR were assessed by
      multivariable logistic regression analysis. In the multivariable analysis,
      independent factors associated with SVR were the attainment of RVR (odds ratio
      (OR) 11, 95% confidence interval (CI) 6.15-20.69; p<0.0001), patient age <=40
      years (OR 4.2, 95% CI 2.30-7.96, p<0.0001), and a low pre-treatment viral load
      (<=8 * 10(5) IU/ml; OR 3.4, 95% CI 1.87-6.25; p<0.0001). The effect of RVR in
      patients aged >40 years was more pronounced than in those aged <=40 years: 81.1%
      of patients aged >40 years who achieved an RVR had an SVR, whereas only 7.5% of
      patients aged >40 years who did not achieve an RVR had an SVR (p<0.05).
      CONCLUSIONS: RVR is an independent variable that is predictive of SVR. Moreover
      older patients (>40 years) who achieve an RVR are likely to have an SVR, while
      patients who do not achieve an RVR and who have a high pre-treatment viral load
      (>8 * 10(5) IU/ml) are unlikely to have an SVR.

PMID- 22658874
TI  - Poleward bound: biological impacts of Southern Hemisphere glaciation.
AB  - Postglacial recolonisation patterns are well documented for the Northern
      Hemisphere biota, but comparable processes in the Southern Hemisphere have only
      recently been examined. In the largely terrestrial Northern Hemisphere, recession
      of ice after the Last Glacial Maximum (LGM) allowed various taxa, including slow
      moving terrestrial species, to migrate poleward. By contrast, the Southern
      Hemisphere polar region is completely ringed by ocean, and recolonisation of
      Antarctica and the sub-Antarctic islands has thus presented considerable
      challenges. Although a few highly dispersive marine species have been able to
      recolonise postglacially, most surviving high-latitude taxa appear to have
      persisted throughout glacial maxima in local refugia. These contrasting patterns
      highlight the importance of habitat continuity in facilitating biological range
      shifts in response to climate change.

PMID- 22658875
TI  - It's not about technology, but community practice: a response to Scotland and
      Wood.

PMID- 22658876
TI  - Global disparity in the resilience of coral reefs.
AB  - The great sensitivity of coral reefs to climate change has raised concern over
      their resilience. An emerging body of resilience theory stems largely from
      research carried out in a single biogeographic region; the Caribbean. Such
      geographic bias raises the question of transferability of concepts among regions.
      In this article, we identify factors that might predispose the Caribbean to its
      low resilience, including faster rates of macroalgal growth, higher rates of
      algal recruitment, basin-wide iron-enrichment of algal growth from aeolian dust,
      a lack of acroporid corals, lower herbivore biomass and missing groups of
      herbivores. Although mechanisms of resilience are likely to be ubiquitous, our
      analysis suggests that Indo-Pacific reefs would have to be heavily degraded to
      exhibit bistability or undergo coral-macroalgal phase shifts.

PMID- 22658878
TI  - Phylogeny, ecology, and the coupling of comparative and experimental approaches.
AB  - Recent progress in the development of phylogenetic methods and access to
      molecular phylogenies has made comparative biology more popular than ever before.
      However, determining cause and effect in phylogenetic comparative studies is
      inherently difficult without experimentation and evolutionary replication. Here,
      we provide a roadmap for linking comparative phylogenetic patterns with
      ecological experiments to test causal hypotheses across ecological and
      evolutionary scales. As examples, we consider five cornerstones of ecological and
      evolutionary research: tests of adaptation, tradeoffs and synergisms among
      traits, coevolution due to species interactions, trait influences on lineage
      diversification, and community assembly and composition. Although several
      scenarios can result in a lack of concordance between historical patterns and
      contemporary experiments, we argue that the coupling of phylogenetic and
      experimental methods is an increasingly revealing approach to hypothesis testing
      in evolutionary ecology.

PMID- 22658879
TI  - The effect of therapies for osteoporosis on spine fusion: a systematic review.
AB  - BACKGROUND CONTEXT: Fusion of the spine requires de novo bone formation and
      remodeling, processes that rely heavily on the action of the osteoblast and
      osteoclast. Bisphosphonate drugs and intermittent parathyroid hormone (PTH)
      therapy are widely prescribed to treat osteoporosis and act on the
      osteoblast/osteoclast complex. The impact of these medications on spine fusion is
      not known. PURPOSE: To evaluate the available evidence on the potential impact of
      bisphosphonates and PTH on fusion rate and fusion quality in spinal arthrodesis.
      STUDY DESIGN: A systematic review of the literature. PATIENT SAMPLE: All
      available literature regarding the impact of bisphosphonates and PTH on spinal
      fusion. OUTCOME MEASURES: Fusion rate and histologic, microstructural, or
      biomechanical measures of fusion quality. METHODS: A systematic review of the
      literature published between 1980 and 2011 was conducted using major electronic
      databases. The results of studies meeting criteria for inclusion were then
      aggregated and examined for consensus on the effect of these medications on spine
      fusion. RESULTS: The literature contained 18 animal studies and one clinical
      trial investigating the impact of these medications on spine fusion. Most animal
      studies evaluating the impact of bisphosphonates on fusion rate have not found
      statistically significant changes with treatment, although this fact may be
      attributable to low statistical power. The animal literature does suggest that
      bisphosphonate therapy results in a less histologically mature fusion mass;
      however, the impact of these changes on fusion mass biomechanics is unclear. The
      only available human study suggests that these bisphosphonates may increase the
      radiographically defined fusion rate but did not demonstrate an impact on
      clinical outcome. In animals, PTH improves the fusion rate and fusion mass
      microstructure, but data on its effect on fusion mass biomechanics are lacking.
      No studies have evaluated the impact of PTH on spine fusion in humans.
      CONCLUSIONS: In animals, bisphosphonate therapy appears to impede maturation of
      the fusion mass, with an unclear effect on mechanical strength. This effect was
      not seen in the lone human study, which suggested that these medications improved
      the radiographically defined fusion rate. The available animal studies on
      intermittent PTH treatment suggest that it may improve fusion rate and fusion
      mass microstructure. Given the widespread use of these agents, further
      investigation into their impact on human spine fusion is necessary to inform the
      care of patients with osteoporosis who are undergoing spine surgery.

PMID- 22658880
TI  - Decision making in the chronic pain patient (and rodent): contribution of the
      orbitofrontal cortex.

PMID- 22658881
TI  - Assessment and validation of prognostic models for poor functional recovery 12
      months after whiplash injury: a multicentre inception cohort study.
AB  - Uncertainty surrounds prognostic factors after whiplash injury. Previously we
      identified a prognostic model for 6-month pain-related disability in a cohort of
      80 participants with acute whiplash. Predictors included initial disability,
      older age, decreased cold pain thresholds, decreased neck rotation movement,
      posttraumatic stress symptoms and decreased sympathetic vasoconstriction. The
      objective of this study was to externally validate this model. In a multicentre
      inception cohort study, 286 participants with acute whiplash (I, II or III) were
      assessed at <3 weeks and 12 months after injury. The Neck Disability Index (NDI)
      was the outcome. Observed and predicted NDI scores were generated using the
      published equation of the original model. Model discrimination between
      participants with no or mild disability from those with moderate to severe
      disability was examined by receiver operating characteristic curves. Initial NDI
      and cold pain threshold predicted current observed 12-month NDI scores (r(2) =
      0.50, 95% confidence interval 0.42 to 0.58). There was a significant site effect,
      and the estimated marginal mean +/- SE of 12-month NDI for Iceland (27.6 +/-
      1.79%) was higher than the other 3 sites (Melbourne 11.2 +/- 5.03%, Canada 16.4
      +/- 2.36%, Brisbane 16.8 +/- 1.17%). After adjusting for site, age and Impact of
      Events Scale scores regained significance (r(2) = 0.56, 95% confidence interval
      0.48 to 0.64). The tested model was not precise in predicting NDI as a continuous
      variable. However, it found good accuracy to discriminate participants with
      moderate to severe disability at 12 months (area under the receiver operating
      characteristic curve 0.89 [95% confidence interval 0.84-0.94], P<.001) which is
      clinically useful.

PMID- 22658882
TI  - Prognostic significance of primary Gleason pattern in Japanese men with Gleason
      score 7 prostate cancer treated with radical prostatectomy.
AB  - OBJECTIVES: To evaluate the significance of the primary Gleason pattern in
      patients with Gleason score (GS) 7 prostate cancer treated with radical
      prostatectomy. MATERIALS AND METHODS: This study included 959 consecutive
      Japanese men who underwent radical prostatectomy without neoadjuvant therapies
      and were subsequently diagnosed as having GS 7 prostate cancer based on the
      modified International Society of Urological Pathology (ISUP) 2005 Gleason
      grading system. RESULTS: Of these 959 patients, 666 (69.4%) and 293 (30.6%) had
      GS 3+4 and GS 4+3 tumors, respectively. There were significant differences in the
      prostate-specific antigen (PSA) level, biopsy GS, pathologic T stage, lymphatic
      invasion, microvenous invasion, and perineural invasion between these 2 groups.
      During the mean observation of 48.9 months, biochemical recurrence occurred in
      211 patients (22.0%), and there was a significant difference in the biochemical
      recurrence-free survival between patients with GS 3+4 tumors and those with GS
      4+3 tumors. Of several factors examined, biochemical recurrence-free survival was
      significantly associated with the PSA level, biopsy Gleason score, capsular
      penetration, seminal vesicle invasion, surgical margin status, lymphatic
      invasion, microvenous invasion, perineural invasion, and primary Gleason pattern,
      among which the PSA level, capsular penetration, seminal vesicle invasion, and
      surgical margin status, but not primary Gleason pattern, appeared to be
      independent predictors of biochemical recurrence. CONCLUSIONS: Despite the lack
      of an independent significance, primary Gleason pattern based on the modified
      ISUP 2005 Gleason grading system is shown to be significantly associated with the
      biochemical outcome of Japanese men with GS 7 prostate cancer.

PMID- 22658883
TI  - Sorafenib or sunitinib as postoperative adjuvant therapy for Chinese patients
      with locally advanced clear cell renal cell carcinoma at high risk for disease
      recurrence.
AB  - OBJECTIVE: To evaluate the efficacy and safety of targeted agents (sorafenib and
      sunitinib) as postoperative adjuvant therapy in Chinese patients with clear cell
      renal cell carcinoma (CC-RCC) who are at high risk for disease recurrence.
      MATERIALS AND METHODS: Forty-three patients treated at our center between
      December 2007 and December 2010 with locally advanced CC-RCC who were at a high
      risk for disease recurrence were enrolled into the study. The criteria for high
      risk of CC-RCC recurrence postoperatively were defined according to the Mayo
      Clinic stage, size, grade, and necrosis (SSIGN) score for CC-RCC. After radical
      nephrectomy, patients received either sorafenib (group A, n = 20) or sunitinib
      (group B, n = 23) and were followed up for at least 1 year to determine the
      efficacy and safety of the test products. The duration of maintenance targeted
      medication treatment was approximately 1 year. Group C consisted of 388 CC-RCC
      patients treated at our center between 1992 and 2007, who were at high risk for
      disease recurrence and who received no adjuvant therapy. RESULTS: The demography
      characteristics were similar among the 3 groups. The overall rate of recurrence
      in groups A and B was not different (15.0% and 17.4% (P > 0.05), respectively),
      which was lower than that of group C (38.7%, P < 0.05 compared with groups A and
      B). Disease-free survival (DFS) was longer in groups A and B (18.9 +/- 5.9 months
      and 16.9 +/- 6.1 months [P > 0.05], respectively), compared with group C (13.3 +/
      7.2 months, P < 0.05 compared with groups A and B). The common adverse effects
      of targeted therapy included hand-foot syndrome, fatigue, diarrhea, taste
      disturbance, rash, hypertension, alopecia, stomatitis, neutropenia, nausea,
      pruritus, hypothyroidism in groups A and B. The adverse effects were mild in both
      groups and the incidence was not significantly different between groups A and B.
      CONCLUSIONS: Targeted adjuvant therapy postoperatively with sorafenib or
      sunitinib in patients with CC-RCC who are at a high risk for disease recurrence
      was well tolerated and effective in reducing the rate of CC-RCC recurrence in
      these patients. This study is an attempt to assess the utility of adjuvant
      tyrosine kinase inhibitors (TKIs) after surgery for renal carcinoma. The
      apparently improved outcomes, compared with a historical control population, are
      of sufficient interest to support the continuation of an ongoing randomized
      clinical trial to validate the hypothesis.

PMID- 22658884
TI  - Prostate-specific membrane antigen-based imaging.
AB  - Prostate cancer (CaP) is the most common noncutaneous malignancy affecting men in
      North America. Despite significant efforts, conventional imaging of CaP does not
      contribute to patient management as much as imaging performed for other common
      cancers. Given the lack of specificity in conventional imaging techniques, one
      possible solution is to screen for CaP-specific antigenic targets and generate
      agents able to specifically bind. Prostate-specific membrane antigen (PSMA) is
      overexpressed in CaP tissue, with low levels of expression in the small
      intestine, renal tubular cells, and salivary gland. The first clinical agent for
      targeting PSMA was (111)In-capromab, involving an antibody recognizing the
      internal domain of PSMA. The second- and third-generation humanized PSMA binding
      antibodies have the potential to overcome some of the limitations inherent to
      capromab penditide (i.e., inability to bind to live CaP cells). One example is
      the humanized monoclonal antibody J591 (Hu mAb J591) that was developed primarily
      for therapeutic purposes but also has interesting imaging characteristics,
      including the identification of bone metastases in CaP. The major disadvantage of
      use of mAb for imaging is slow target recognition and background clearance in an
      appropriate time frame for diagnostic imaging. Urea-based compounds, such as
      small molecule inhibitors may also present promising agents for CaP imaging with
      single-photon emission computed tomography (SPECT) and positron emission
      tomography (PET). Two such small-molecule inhibitors targeting PSMA, MIP-1072,
      and MIP-1095 have exhibited high affinity for PSMA. The uptake of (123)I-MIP-1072
      and (123)I-MIP-1095 in CaP xenografts have imaged successfully with favorable
      properties amenable to human trials. While advances in conventional imaging will
      continue, Ab and small molecule imaging exemplified by PSMA targeting have the
      greatest potential to improve diagnostic sensitivity and specificity.

PMID- 22658885
TI  - Dried urine spots for detection and quantification of cytomegalovirus in
      newborns.
AB  - Dried urine spots (DUS) have been reported to provide a simple screening tool for
      congenital cytomegalovirus (CMV) infection. We developed a standardized method
      for CMV quantification from DUS. Two applications of 20 MUL urine remained within
      the rim of the filter paper disc and were used to determine the analytical
      performance of Towne CMV spiked into urine and applied on the discs. The
      measurable range spanned 3.7 to >=8.0 log(10) copies/mL. The detection limit was
      22 DNA copies/disc. Urine samples from congenitally infected newborns and
      negative controls were either diluted 1:10 or applied on filter paper at the same
      volume. DNA copy number from DUS correlated well with copy number from 1:10
      diluted urine, although there was a trend for lower levels from DUS (0.3 log(10)
      difference). Our standardized method for CMV detection and quantification may
      facilitate CMV studies in resource-limited areas and allow for longitudinal
      monitoring of viral loads in treated infants.

PMID- 22658886
TI  - Assessing paternities with inconclusive STR results: The suitability of bi
      allelic markers.
AB  - In paternity testing the genetic profiles of the individuals are used to compare
      the relative likelihoods of the alleged father and the child being related as
      father/offspring against, usually, being unrelated. In the great majority of the
      cases, analyses with the widely used sets of short tandem repeat markers (STRs)
      provide powerful statistical evidence favouring one of the alternative
      hypotheses. Nevertheless, there are situations where the final statistical result
      is ambiguous, mostly because the alleged father shows incompatible genotypes at a
      few loci along with a very high paternity index in the remaining systems. In
      these cases, the possibility that the alleged father is actually a close relative
      of the real one (son, father or brother) can reasonably be raised. In such cases,
      when the statistical evidence obtained is considered as insufficient, the common
      practice is to extend the set of analysed markers. In this context, many authors
      have suggested that bi-allelic markers, such as single nucleotide (SNP) or
      insertion/deletion (Indel) polymorphisms, are markers of choice, as they are
      incomparably less prone to mutation than STRs. In this work we address the
      soundness of this claim and the consequences of this strategy, analyzing the a
      priori odds both for (a) expected number of Mendelian incompatibilities, and (b)
      expected values for the final likelihood ratios. Moreover, one hundred real pairs
      of second degree relatives, typed for two sets of markers: 15 STRs plus 38
      Indels, were used to simulate paternity testing. Our data show that, for the
      number of markers commonly considered, the results from an extended battery of
      SNPs or Indels should be interpreted with caution when relatives are possibly
      involved.

PMID- 22658887
TI  - Transjugular and transseptal treatment of a degenerated mitral valve prosthesis
      with a balloon-expandable biological valve.
AB  - In selected high-risk patients, trans-catheter valve implantation is an emerging
      therapy for a degenerated bioprosthesis in need of repeated valve replacement.
      During the last two years, valve-in-valve implantations have mainly been
      performed in the aortic position and only rarely in the mitral position. Here we
      describe for the first time the case of a 62 year-old female with severe mitral
      regurgitation of a degenerated Carpentier Edwards bioprosthesis treated by
      transjugular, transseptal implantation of a SAPIEN-XT valve. In conclusion this
      case, together with previous reports, show the feasibility and safety of
      percutaneous valve-in-valve implantations to treat a degenerated bioprosthesis.

PMID- 22658888
TI  - Endobronchial ultrasonography with transbronchial needle aspiration to sample a
      solitary substernal thyroid nodule: a new approach.
AB  - Sampling of solitary thyroid nodules (STNs) is a common procedure performed for
      cytological diagnosis. The easiest and safest method is ultrasound guided fine
      needle aspiration biopsy (US-FNAB). This technique is usually performed under
      local anaesthesia in an office setting. In contrast, sampling a substernal STN
      could prove to be more difficult and problematic, and sometimes requires more
      invasive procedures. We describe a case of substernal thyroid nodule, where
      malignancy was excluded using endobronchial ultrasonography with transbronchial
      fine needle aspiration (EBUS-TBNA). We emphasise the feasibility and safety of
      EBUS-TBNA in sampling retrosternal thyroid nodules. In appropriate settings, this
      procedure can help avoid more invasive testing, and subsequently decrease the
      cost and complications.

PMID- 22658889
TI  - Acute intrathoracic intestinal strangulation diagnosed by transthoracic
      echocardiography.
AB  - Transthoracic echocardiography plays a central role in diagnosing a variety of
      cardiac and pericardial disorders. However its use in identifying extra-cardiac
      thoracic pathology is less well recognised. We describe an unusual case of
      intrathoracic intestinal strangulation detected by transthoracic
      echocardiography. The recognition of bowel loops within the left hemithorax
      enabled rapid confirmatory computed tomographic imaging and subsequent life
      saving surgery. This case demonstrates the utility of bedside echocardiography in
      the assessment of intrathoracic pathology and emphasises the need for
      cardiologists to be familiar with the echocardiographic appearance of these
      disorders.

PMID- 22658890
TI  - Perceptions of the screening mammography experience by Hispanic and non-Hispanic
      White women.
AB  - PURPOSE: To uncover perceptive differences in mammography experiences (from
      scheduling the mammography appointment to receipt and reporting of mammography
      results) between women from two different racial/ethnic groups. METHODS: Focus
      groups (n = 9) were conducted with Hispanic, and non-Hispanic White women (n =
      88) who were aged 40 years or older and had a mammogram within the preceding 36
      months. We used a qualitative ethnographic approach with content analysis to
      identify key categories present in the transcripts and domain analysis to
      discover domains of meaning. A matrix was designed to determine which domains
      differed by racial/ethnic group. The primary mammography-related topics of focus
      group discussion included 1) the scheduling process, 2) the day of the mammogram,
      3) receipt of results, and 4) recommendations to improve the mammography process.
      MAIN FINDINGS: Six domains uniquely described issues women of the differing
      racial/ethnic groups experience and perceive as important. Hispanic women
      highlighted embarrassment surrounding the examination and fear of negative news
      about their mammography results. Non-Hispanic White women focused on instructions
      given before or during the examination as a critical process feature.
      CONCLUSIONS: Perceptions of the mammography experience vary by race/ethnicity.
      Mammography experiences might be improved through enhanced sensitivity of
      healthcare personnel to cultural differences in perceptions of mammogram testing.
      Future research to investigate the extent to which the domains of meanings
      uncovered in this study influence a women's decision to return for routine
      mammograms would be of great value.

PMID- 22658891
TI  - Comprehensive healthcare: why is the inclusion of reproductive health
      controversial for women but not men?

PMID- 22658892
TI  - Fever of unknown origin (FUO) and a renal mass: renal cell carcinoma, renal
      tuberculosis, renal malakoplakia, or xanthogranulomatous pyelonephritis?
AB  - Often patients with fevers of unknown origin (FUOs) present with loss of
      appetite, weight loss, and night sweats, without localizing signs. Some are found
      to have a renal mass during diagnostic evaluation. In patients with FUOs and a
      renal mass, the differential diagnosis includes renal tuberculosis, renal cell
      carcinoma (hypernephroma), renal malakoplakia, and xanthogranulomatous
      pyelonephritis. A 68-year-old woman presented with an FUO during her diagnostic
      workup. She manifested an irregularly enlarged kidney on abdominal computed
      tomography (CT) scan, as well as a highly elevated erythrocyte sedimentation rate
      of more than 100 mm/hour, an elevated serum ferritin level, and chronic
      thrombocytosis, which favored a diagnosis of renal cell carcinoma. Renal
      malakoplakia and renal tuberculosis comprised further differential diagnostic
      considerations. Microscopic hematuria may be present with any of the disorders in
      the differential diagnosis, but was absent in this case. An abdominal CT scan was
      suggestive of xanthogranulomatous pyelonephritis. Because of concerns regarding
      renal cell carcinoma, the patient received a nephrectomy. The pathologic
      diagnosis was of xanthogranulomatous pyelonephritis, without renal cell
      carcinoma.

PMID- 22658893
TI  - The revolving door between hospital and community: extended-spectrum beta
      lactamase-producing Escherichia coli in Dublin.
AB  - BACKGROUND: Escherichia coli that produce extended-spectrum beta-lactamases
      (ESBLs) are an increasing cause of healthcare-associated infection, and community
      healthcare facilities may be a reservoir for important epidemic clones. AIM: To
      characterize retrospectively and investigate the epidemiology of ESBL-producing
      E. coli collected in a Dublin hospital, during 2009 and 2010, and to investigate
      the dissemination of specific clones within hospital and community healthcare
      facilities. METHODS: Pulsed-field gel electrophoresis (PFGE) was used to
      determine the genetic relatedness of 100 ESBL-producing E. coli isolates.
      Phylogenetic groups were determined and the O25b-ST131 clone identified in the
      collection. The genetic data were correlated with antimicrobial susceptibility,
      clinical and demographic data to explore the epidemiology of specific clones.
      FINDINGS: Phylogenetic groups B2 (62%) and D (18%) were the most common and were
      associated with non-urinary isolates (P<0.0001 by Fisher's exact test). PFGE
      revealed 12 clusters (>= 80% similarity), the largest of which clustered with the
      epidemic UK strain A. Residents of long-term care facilities (LTCFs) in the
      community exclusively carried the O25b-ST131 clone and phylogenetic groups B2 and
      D. CONCLUSIONS: E. coli O25b-ST131 is largely responsible for ESBL-producing E.
      coli in LTCFs in Dublin. The distribution of ESBL-producing E. coli in our
      hospital and community highlights a 'revolving door' through which these
      resistant bacteria spread and disseminate.

PMID- 22658894
TI  - Expression of 14-3-3gamma in patients with breast cancer: correlation with
      clinicopathological features and prognosis.
AB  - AIM: Protein 14-3-3gamma is an important member of the 14-3-3 family that play
      important roles in the regulation of various cellular processes. The aim of the
      study is to investigate the association between 14-3-3gamma expression and the
      clinicopathological features of patients with breast cancer. METHODS: The
      expression of 14-3-3gamma was detected by Western blot in both foci of breast
      cancer and adjacent non-cancerous tissues. In addition, 14-3-3gamma expression
      was analyzed by immunohistochemistry in 60 clinicopathologically characterized
      breast cancer cases. The association of 14-3-3gamma expression with survival of
      the patients were analyzed. RESULTS: The expression level of 14-3-3gamma protein
      in breast cancer were significantly higher than that in non-cancerous mammary
      gland tissues. Moreover, high expression of 14-3-3gamma correlated with tumor
      size and tumor grade (all P<0.05). Patients with high 14-3-3gamma expression had
      worse overall survival rate than that with low expression (P < 0.05).
      Furthermore, multivariate analysis showed that 14-3-3gamma expression was an
      independent predictor of overall survival (HR, 0.196; 95%CI, 0.043-0.892; P =
      0.035). CONCLUSIONS: Our data suggest for the first time that the increased
      expression of 14-3-3gamma in breast cancer is associated significantly with tumor
      progression and poor prognosis. 14-3-3gamma may be a novel and potential
      prognostic marker for breast cancer.

PMID- 22658896
TI  - Risk stratification of plasma cell neoplasm: insights from plasma cell-specific
      cytoplasmic immunoglobulin fluorescence in situ hybridization (cIg FISH) vs.
      conventional FISH.
AB  - We directly compared the results of routine fluorescence in situ hybridization
      (FISH) and plasma cell-specific cytoplasmic immunoglobulin (cIg) FISH from 75
      paired samples for myeloma risk stratification. CIg FISH improves test
      specificity and sensitivity and tends to eliminate borderline results. It proves
      that most plasma cells (PCs) consistently carry the abnormality in myelomas with
      an IGH translocation, whereas routine FISH detects these cells only at variably
      low levels. BACKGROUND: Routine cytogenetic analysis of plasma cell neoplasms
      (PCNs) has a low sensitivity. Conventional fluorescence in situ hybridization
      (FISH) is not plasma cell (PC) specific and results are diluted by other cells in
      the sample. Although PC-specific FISH testing has been recommended for multiple
      myeloma (MM) risk stratification, eg, by combining cytoplasmic immunoglobulin
      (cIg) staining with FISH, the benefits of cIg FISH have never been directly
      demonstrated in a controlled study. PATIENTS AND METHODS: Seventy-five samples
      from patients with PCNs were analyzed by concomitant conventional FISH and cIg
      FISH with probes for t(4;14), t(11;14), t(14;16), -13, 17p-, and +3. The results
      were compared for their reliability, specificity, and consistency. RESULTS: Apart
      from marginally improving detection threshold in samples with low PC burden, cIg
      FISH identified more abnormal cases (50 vs. 47 cases) and more chromosome
      abnormalities (113 vs. 103 events) than did conventional FISH. It differentiated
      del(13q) in myelodysplasia from MM. Remarkably, cIg FISH consistently identified
      a high percentage of abnormal PCs in all cases. It detected IGH translocation in
      78% to 100% of PCs in all but 2 positive cases, whereas conventional FISH
      detected 0% to 46% in these cases (median, 91% vs. 9%). The abnormal cells found
      in patients with 17p- were 19% to 96% by cIg FISH vs. 0% to 13% by conventional
      FISH (median, 54% vs. 9%). Cases with insufficient PCs for cIg FISH had only
      normal conventional FISH results. CONCLUSION: CIg FISH improves reliability of
      FISH testing for PCNs by eliminating borderline results. In myelomas with an IGH
      translocation, myeloma cells invariably carry the abnormality.

PMID- 22658895
TI  - A randomized controlled trial of an intensive insulin regimen in patients with
      hyperglycemic acute lymphoblastic leukemia.
AB  - Hyperglycemia during hyper-CVAD (fractionated cyclophosphamide, vincristine,
      doxorubicin, and dexamethasone alternating with methotrexate and high-dose
      cytarabine, with methylprednisolone premedication) chemotherapy is associated
      with poor outcomes of acute lymphoblastic leukemia (ALL). To examine whether
      intensive insulin therapy could improve outcomes, a randomized trial was
      conducted that compared glargine plus aspart vs. conventional therapy. Intensive
      insulin did not improve ALL clinical outcomes despite improved glycemic control.
      Secondary analysis suggests that the choice of antidiabetic pharmacotherapy may
      influence ALL outcomes. INTRODUCTION: Hyperglycemia during hyper-CVAD
      (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone
      alternating with methotrexate and high-dose cytarabine, with methylprednisolone
      premedication) chemotherapy is associated with poor outcomes of acute
      lymphoblastic leukemia (ALL). PATIENTS AND METHODS: To examine whether an
      intensive insulin regimen could improve outcomes compared with conventional
      antidiabetic pharmacotherapy, a randomized trial was conducted that compared
      glargine plus aspart vs. conventional therapy (control). Between April 2004 and
      July 2008, 52 patients newly diagnosed with ALL, Burkitt lymphoma, or
      lymphoblastic lymphoma who were on hyper-CVAD in the inpatient setting and had a
      random serum glucose level >180 mg/dL on >=2 occasions during chemotherapy were
      enrolled. RESULTS: The trial was terminated early due to futility regarding ALL
      clinical outcomes despite improved glycemic control. Secondary analysis revealed
      that molar insulin-to-C-peptide ratio (I/C) > 0.175 (a surrogate measure of
      exogenous insulin usage) was associated with decreased overall survival, complete
      remission duration and progression-free survival (PFS), whereas metformin and/or
      thiazolidinedione usage were associated with increased PFS. In multivariate
      analyses, factors that significantly predicted short overall survival included
      age >= 60 years (P = .0002), I/C >= 0.175 (P = .0016), and average glucose level
      >= 180 mg/dL (P = .0236). Factors that significantly predicted short PFS included
      age >= 60 years (P = .0008), I/C >= 0.175 (P = .0002), high systemic risk (P =
      .0173) and average glucose level >= 180 mg/dL (P = .0249). I/C >= 0.175 was the
      only significant (P = .0042) factor that predicted short complete remission
      duration. CONCLUSIONS: A glargine-plus-aspart intensive insulin regimen did not
      improve ALL outcomes in patients with hyperglycemia. Exogenous insulin may be
      associated with poor outcomes, whereas metformin and thiazolidinediones may be
      associated with improved outcomes. Analysis of these results suggests that the
      choice of antidiabetic pharmacotherapy may influence ALL outcomes.

PMID- 22658898
TI  - Differential, size-dependent sensory neuron involvement in the painful and ataxic
      forms of primary Sjogren's syndrome-associated neuropathy.
AB  - Primary Sjogren's syndrome (pSS)-associated neuropathy manifests a wide variety
      of peripheral neuropathies that may show overlap among the neuropathic forms. In
      this report, we describe histopathological findings of two autopsy cases with pSS
      associated neuropathy; one of them manifested the painful form and another showed
      ataxic form. The population of dorsal root ganglion (DRG) neurons and the density
      of myelinated fibers in the dorsal spinal root were variably reduced among spinal
      segments in both forms. In the painful form, there was a prominent reduction of
      small neurons, while in the ataxic form, large neurons were predominately lost.
      In accordance with the degree of the DRG cell loss, the modality of nerve fiber
      loss in the dorsal spinal roots and sural nerve correlated well with the
      corresponding DRG neuron loss. Prominent CD8+ T lymphocyte infiltration was
      present in the DRG, sympathetic ganglion, epineurial and perineurial space
      throughout the peripheral nerve trunks, and visceral organs, including the
      submandibular gland of both forms. Although the size of affected DRG neurons is
      different, these two forms share a similar causal mechanism, namely, cytotoxic
      autoimmunity to ganglion neurons, which may be one of a continuum of etiological
      factors. This hypothesis may have an impact on therapeutic approach.

PMID- 22658899
TI  - Three cases of Creutzfeldt-Jakob disease with prion protein gene codon180
      mutation presenting with pathological laughing and crying.
AB  - Although there are no reports of pathological laughing and crying being observed
      in patients with Creutzfeldt-Jakob disease (CJD), the author experienced three
      patients with CJD with prion protein gene codon180 mutation (V180I CJD) who
      showed this characteristic clinical finding. This finding was observed from the
      early disease stage in all 3 patients and continued for several months. Startle
      reaction was also remarkable in all patients, although myoclonus was generally
      mild. The dissociation between the startle reaction and myoclonus was suspected
      to be another feature of V180I CJD. The pathological laughing and crying co
      occured with the startle reaction and stopped right before the onset of akinetic
      mutism, and the degree of both symptoms was almost parallel during this period.
      On the basis of MRI and autopsy findings, pathological laughing and crying was
      suspected of being induced by the widespread cerebral cortical involvement that
      is characteristic of V180I CJD. From the present observations, the author
      speculated that pathological laughing and crying may be a comparatively frequent
      observation in V180I CJD patients.

PMID- 22658897
TI  - Cysticerci-related single parenchymal brain enhancing lesions in non-endemic
      countries.
AB  - OBJECTIVE: Review of case reports and case series of patients with single
      cysticercus granulomas in non-endemic countries to determine the characteristics
      of this form of neurocysticercosis in these regions. METHODS: MEDLINE and manual
      search of patients with single cysticercus granulomas diagnosed in non-endemic
      countries from 1991 to 2011. Abstracted data included: demographic profile,
      clinical manifestations, form of neurocysticercosis, and whether the disease
      occurred in immigrants, international travelers, or citizens from non-endemic
      countries who had never been abroad. RESULTS: A total of 77 patients were found.
      Of these, 61 (79%) were diagnosed since the year 2000. Thirty-four patients (44%)
      patients were immigrants from endemic countries, 18 (23%) were international
      travelers returning from disease-endemic areas, and the remaining 25 (33%) were
      citizens from non-endemic countries who had never been abroad. Most immigrants
      and international travelers became symptomatic two or more years after returning
      home. Countries with the most reported patients were Kuwait (n=18), UK (n=11),
      Australia (n=8), USA (n=7), Japan (n=6), and Israel (n=5). CONCLUSIONS: A single
      cerebral cysticercus granuloma in a non-endemic country is not a rare event. As
      seen in endemic regions, these cases have a good prognosis although more surgical
      procedures are performed in non-endemic countries, likely reflecting a decrease
      of diagnostic suspicion for cysticercosis and an increased availability of
      surgical options. The mean age of the reported cases was 25 years, and immigrants
      most often developed the disease greater than two years after arrival into a non
      endemic area, suggesting a significant delay between infection and symptoms.
      However, some may have been infected and developed the disease while residing in
      non-endemic countries.

PMID- 22658900
TI  - Virus like particle based strategy to elicit HIV-protective antibodies to the
      alpha-helic regions of gp41.
AB  - Natural antibodies to gp41 inhibit HIV-1 replication through the recognition of
      two different regions, corresponding to the leucine zipper motif in the HR1 alpha
      helix and to another motif within HR2 region, hosting 2F5 and 4E10 epitope. This
      study aimed at reproducing such protective responses through VLP vaccination. Six
      regions covering the alpha-helical regions of gp41 were conjugated to the surface
      of AP205 phage-based VLPs. Once administered in mice via systemic or mucosal
      route, these immunogens elicited high titers of gp41-specific IgG. Immunogenicity
      and HIV infectivity reduction were obtained either with HR2 regions or with
      peptides where aminoacid strings were added to either the C-terminus or N
      terminus of core epitope in HR1 region. Antibody-dependent cell cytotoxicity
      (ADCC) activity was induced by one of the HR2 epitopes only. These results may
      have relevant implications for the development of new vaccinal approaches against
      HIV infection.

PMID- 22658902
TI  - Chronic unpredictable mild stress affects myocardial metabolic profiling of SD
      rats.
AB  - Depression is frequently comorbid with cardiovascular diseases (CVDs), but a full
      understanding of the mechanisms is still on its way. Chronic unpredictable mild
      stress (CUMS) model is a commonly used model to mimic clinical depression, here
      we present a GC/MS-based metabolic profiling approach to investigate myocardial
      metabolic changes of CUMS SD rats. Principal Component Analysis (PCA) and Partial
      Least Squares-Discriminant Analysis (PLS-DA) were utilized to reveal differences
      between the model and control group. This study found that molecules proved
      cardioprotective involving glutamine (P=0.019) and inosine (P=0.013), fatty acid
      (9,12-octadecadienoic acid, P=0.002; hexadecanoic acid, P=0.006; octadecanoic
      acid, P=0.030) which serve as the major energy source of heart and collagen
      molecule precursor proline (P=0.036) had down-regulated in CUMS model group.

PMID- 22658901
TI  - Influenza M1 VLPs containing neuraminidase induce heterosubtypic cross
      protection.
AB  - Influenza virus like particles (VLPs) containing hemagglutinin were previously
      demonstrated to induce protection against the homologous strains. However, little
      information is available on the protective role of neuraminidase (NA), the second
      major glycoprotein. In this study, we developed VLPs (NA VLPs) containing NA and
      M1 derived from A/PR/8/34 (H1N1) influenza virus, and investigated their ability
      to induce protective immunity. Intranasal immunization with NA VLPs induced serum
      antibody responses to H1N1 and H3N2 influenza A viruses as well as significant
      neuraminidase inhibition activity. Importantly, mice immunized with NA VLPs were
      100% protected against lethal infection by the homologous A/PR/8/34 (H1N1) as
      well as heterosubtypic A/Philippines/82 (H3N2) virus, although body weight loss
      was observed after lethal challenge with heterosubtypic H3N2 virus. The present
      study therefore provides evidence that influenza VLPs containing M1 and NA are
      capable of inducing immunity to homologous as well as antigenically distinct
      influenza A virus strains.

PMID- 22658903
TI  - Topotecan exposure estimation in pediatric acute myeloid leukemia supported by LC
      MS-based drug monitoring and pharmacokinetic analysis.
AB  - Individualization of the topotecan dosing can reduce inter-patient variability,
      toxicity, and at the same time increases chemotherapy efficacy. Topotecan dosing
      based on simultaneous drug monitoring and pharmacokinetic analysis can yield more
      accurate and precise estimation of the topotecan systemic exposure than that
      attainable with the fixed dosing approach. Therefore, a combined approach could
      provide a tool assisting the clinicians in individualization of the topotecan
      dosing. The aim of the study was to estimate the topotecan exposure in pediatric
      patients with acute myeloid leukemia (AML) based on the plasma concentration-time
      data and using the pharmacokinetic analysis. The primary goal was achieve the
      correct estimation of the target plasma area against the topotecan concentration
      time curve (AUC) in a 5 day course of cladribine followed by monitored topotecan
      in pediatric patients with recurrent/refractory AML. A sensitive and selective
      reversed-phase liquid chromatographic-mass spectrometry (LC-MS) assay was
      developed to quantify total topotecan in the human plasma samples. This method,
      with its lower quantification limit of 1 ng/ml, was validated over a linear range
      of 1-150 ng/ml. Under the proposed approach, the topotecan dosing was selected so
      as to achieve the final AUC value of 140+/-20 ng/ml h. The presented analytical
      and pharmacokinetic data demonstrate that the proposed approach can be a
      practical, useful, efficient, and accurate tool for individualizing the topotecan
      dosing in children with AML.

PMID- 22658904
TI  - A fully validated method for the simultaneous determination of 11 antidepressant
      drugs in whole blood by gas chromatography-mass spectrometry.
AB  - Antidepressant drugs are widely used for the treatment of depression and other
      psychiatric disorders and as a result they are involved in numerous clinical and
      forensic cases. The aim of this study was the development, optimization and
      validation of a simple, specific and sensitive GC/MS method for the simultaneous
      determination of 11 antidepressant drugs and 4 of their metabolites
      (amitriptyline, citalopram, clomipramine, fluoxetine, fluvoxamine, maprotiline,
      desmethyl-maprotiline, mirtazapine, desmethyl-mirtazapine, nortriptyline,
      paroxetine, sertraline, desmethyl-sertraline, venlafaxine and desmethyl
      venlafaxine) in whole blood. The combination of solid-phase extraction with
      derivatization using heptafluorobutyric anhydride efficiently reduced matrix
      effect and improved sensitivity of the method. In this assay, protriptyline was
      used as internal standard. Absolute recovery values for all analytes were ranged
      from 79.2 to 102.6%. LODs and LOQs were found to be between 0.30-1.50 MUg/L and
      1.00-5.00 MUg/L, respectively. The calibration curves were linear (R(2)>=0.990)
      within the range of 5.00-1000 MUg/L for all analytes. Accuracy expressed as the %
      E(r) was found to be between -12.3 and 12.2%. Precision expressed as the % RSD
      was found to be less than 11.7% for all antidepressants. The developed method
      proved to be suitable for routine work and it was used to successfully analyze
      more than 2500 clinical and forensic blood samples.

PMID- 22658905
TI  - [Small DCIS: Excision alone].

PMID- 22658906
TI  - [Small DCIS: In favour of postoperative radiotherapy].

PMID- 22658907
TI  - [Training...].

PMID- 22658908
TI  - [Permanent tubal hysteroscopic sterilization].
AB  - Tubal sterilization, of common practice all over the world, has had a quick
      spread in France since its legalization in 2001 and the income of a new
      hysteroscopic method. As a matter of fact, France is the second greater country
      for women having Essure(r) and the first country where Essure(r) method forestall
      surgical tubal ligation. Thus we focus on good practice and update knowledge
      about Essure(r) method.

PMID- 22658910
TI  - Meeting report: The International Conference on Human Immunity to Tuberculosis.
AB  - The International Conference on Human Immunity to Tuberculosis, held in April
      2012 in Atlanta, Georgia, USA provided the opportunity to discuss the current
      state of knowledge, important knowledge gaps, and approaches to overcoming
      obstacles to better understand protective and pathological immunity.

PMID- 22658911
TI  - Acute Wharton's duct sialadenitis and submandibular infection.

PMID- 22658909
TI  - A 3D localized surface plasmon resonance biosensor for the study of trivalent
      arsenic binding to the ArsA ATPase.
AB  - A self-assembled 3D hydrogel-nanoparticle composite integrated surface plasmon
      resonance (SPR) sensor is reported here. The novel assembled substrate was
      developed by means of a surface mediated radical co-polymerization process to
      obtain a highly sensitive hydrogel-based thin film that possesses specific
      binding sites for target analytes. Initially, amino group modified gold
      nanoparticles (AuNPs) were covalently linked to acrylic acid monomer. Following
      this, N-isopropylacrylamide (NIPAAm) and AuNPs linked acrylic acid (AAc) monomers
      were randomly co-polymerized by the "grafting from" method in the presence of
      initiator and crosslinker onto the sensing surface. Surface characterization
      techniques were utilized to evaluate the thickness and composition of the
      hydrogel-nanoparticle film. The sensing platform was employed to study the
      binding kinetics and conformational changes of the ArsA ATPase as a consequence
      of binding trivalent arsenicals under a variety of conditions. ArsA, the
      catalytic subunit of the ArsAB arsenite (As(III)) translocating ATPase, is one of
      the five proteins encoded by the arsenical resistance (ars) operon of plasmid
      R773 in cells of Escherichia coli, that confers resistance to trivalent and
      pentavalent salts of the metalloid arsenic. SPR measurements indicate that the 3D
      hydrogel-nanoparticle coated sensors exhibited a higher sensitivity than that of
      the 2D AuNPs decorated sensors. Binding of As(III) to ArsA is greatly facilitated
      by the presence of magnesium ion and ATP.

PMID- 22658912
TI  - The geography of mercury and PCBs in North Carolina's local seafood.
AB  - Mercury and PCBs are used by non-governmental organizations and federal agencies
      to inform seafood safety recommendations. Pollution dynamics suggest
      recommendations on the national scale may be too large to be accurate. We tested
      softshell and hardshell blue crab, white and pink shrimp, oysters, clams, spot,
      and mullet from fishers in each of the three North Carolina fishery districts. We
      measured mercury using EPA method 7473 and PCBs using a commercially available
      ELISA kit. Over 97% of samples were below the Environmental Protection Agency
      levels of concern for both mercury and PCBs. Mercury and PCBs have different
      spatial dynamics, but both differ significantly by water body, suggesting that
      seafood safety recommendations should occur by water body instead of at the
      national scale. This finding supports previous research suggesting that
      differences in water chemistry, terrestrial influence, and flushing time in a
      particular water body control the contaminant load in locally resident species.

PMID- 22658913
TI  - Objective and subjective cognitive impairment following chemotherapy for cancer:
      a systematic review.
AB  - Evidence suggests that some cancer survivors experience cognitive difficulties
      following chemotherapy. However, perceived or subjective cognitive impairment is
      more frequently reported than prevalence revealed by objective assessments. The
      aim of this review was to examine the relationship between subjective and
      objective measures of cognitive impairment following treatment for cancer and to
      determine the number of studies that found a significant relationship between
      these measures of cognition. A comprehensive search for articles, published
      between 1980 and 2012, comparing subjective and objective cognition in cancer
      patients treated with chemotherapy was conducted. Of 818 potentially relevant
      articles, 23 studies met the inclusion criteria for the current review and one
      article was sourced from reference lists of included studies. Only eight of 24
      included studies found a significant relationship between objective and
      subjective measures of cognitive performance. These studies were more likely to
      involve breast cancer patients and to assess the relationship between memory and
      perceived cognitive impairment. The failure to consistently find an association
      between subjective and objective measures of cognition could be explained by
      variations in assessment methods or the definition of impairment. Alternatively,
      objective and perceived cognitive impairment may be unrelated because perceived
      impairment may be an indicator of psychological distress rather than cognitive
      impairment. Despite these discrepancies, patients' perceptions of impairment are
      important due to its significant impact on quality of life. Further research is
      required to explore whether objective measures of everyday functioning better
      predict the impact of chemotherapy related cognitive impairment on daily
      functioning.

PMID- 22658914
TI  - Genetic variability in swine leukocyte antigen class II and Toll-like receptors
      affects immune responses to vaccination for bacterial infections in pigs.
AB  - The genes encoding swine leukocyte antigen (SLA) and Toll-like receptor (TLR) are
      highly polymorphic in pig populations, and likely have influences on infection
      and the effects of vaccination. We explored the associations of different
      genotypes of SLA class II and of the genes TLR1, TLR4, TLR5, and TLR6 with
      antibody responses after vaccination against Erysipelothrix rhusiopathiae (ER)
      and Actinobacillus pleuropneumoniae (APP) serotypes 1, 2, and 5 in 191 Duroc pigs
      maintained under specific pathogen-free conditions. We demonstrated close
      relationships between SLA class II and ER antibody response and between TLR genes
      other than TLR4 and APP antibody responses. Pigs with specific haplotypes in SLA
      class II or TLR5 showed decreased antibody response to ER vaccination or
      increased responses to APP2 and APP5 vaccination, respectively. It might be
      possible to breed for responsiveness to vaccination and to implement new vaccine
      development strategies unaffected by genetic backgrounds of pigs.

PMID- 22658915
TI  - Modern spinal instrumentation. Part 1: normal spinal implants.
AB  - The general radiologist frequently encounters studies demonstrating spinal
      instrumentation, either as part of the patient's postoperative evaluation or as
      incidental to a study performed for another purpose. There are various surgical
      approaches and devices used in spinal surgery with an increased understanding of
      spinal and spinal implant biomechanics drives development of modern fixation
      devices. It is, therefore, important that the radiologist can recognize commonly
      used devices and identify their potential complications demonstrated on imaging.
      The aim of part 1 of this review is to familiarize the reader with terms used to
      describe surgical approaches to the spine, review the function and normal
      appearances of commonly used instrumentations, and understand the importance of
      the different fixation techniques. The second part of this review will
      concentrate on the roles that the different imaging techniques play in assessing
      the instrumented spine and the recognition of complications that can potentially
      occur.

PMID- 22658916
TI  - Haematological parameters in stray dogs seropositive and seronegative to
      Ehrlichia canis in North Trinidad.
AB  - In view of the fact that stray dogs are a reservoir for many diseases, this study
      was undertaken to determine the prevalence of Ehrlichia canis in stray dogs in
      North Trinidad and to evaluate the diagnostic implications of haematological
      alterations associated with seropositivity. Overall, 41 (44.6%) of 92 stray dogs
      were seropositive to E. canis by the indirect immunofluorescent antibody test.
      Dogs, one year of age and older (59.7%) were more likely to be seropositive than
      dogs less than one year old (13.3%) (p<0.001). No significant differences in
      seropositivity between females and males were found. The odds ratios showed that
      seropositive dogs were 3.34 (CI 95%; 1.33-8.59) and 5.17 (CI 95%; 0.19-1.26)
      times more likely to have low platelet counts and elevated total serum protein
      concentrations (p=0.014 and p<0.001, respectively) than seronegative dogs. Lower
      mean platelet counts and a higher mean total protein concentration were
      associated with seropositivity (p<0.01). Mean eosinophil and segmented neutrophil
      counts were elevated in dogs that tested negative for E. canis antibodies
      (p=0.002 and p<0.005, respectively). Other haematological parameters were not
      different between the 2 groups. The high percentage of stray dogs infected with
      E. canis should alert veterinarians to the potential risk of transmission of the
      disease. A comprehensive study possibly using molecular methods such as nested
      PCR should be undertaken to determine how co-infection with other pathogens may
      alter haematological profiles. In general, control of ticks and stray dog
      populations may help to control the spread of tick-borne diseases.

PMID- 22658917
TI  - Biomarkers for the mucopolysaccharidoses: discovery and clinical utility.
AB  - The mucopolysaccharidoses (MPSs), a group of inherited lysosomal storage
      diseases, are complex, progressive, multisystem disorders with extreme clinical
      heterogeneity. The introduction of therapies that target the underlying enzyme
      deficiency in a number of the MPSs has brought to light the need for biomarkers
      that would aid in the evaluation of disease burden and as a means to objectively
      measure therapeutic response in individual patients. It is increasingly
      recognized that due to the extraordinarily complex pathogenesis of the MPSs,
      achieving these goals with a single analyte, such as urinary glycosaminoglycans,
      is unlikely. This recognition has created an impetus for the search for
      clinically useful biomarkers that reflect the disease pathogenesis and that are
      stage- or organ-specific. In this review, the current state of MPS biomarker
      research is discussed, with a focus on clinical utility in the MPSs.

PMID- 22658918
TI  - Novel pathogenic mutations in the glucocerebrosidase locus.
AB  - To determine the frequency of mutations responsible for Gaucher's disease, we
      systematically sequenced the GBA1 gene as part of a molecular characterization of
      73 adult patients in the United Kingdom. Five hitherto unknown pathogenic
      variants were identified, one of which is a splice site change; the others are
      novel missense mutations. Given that GBA1 gene mutations are an important risk
      factor for the development of Parkinson's disease, we contend that a complete
      analysis and molecular characterization of both the known and novel GBA1 variants
      will be needed before the biochemical processes underlying this genetic
      association can be fully understood.

PMID- 22658919
TI  - Endoscopic ferromagnetic object retrieval by use of a simple magnet (with video).

PMID- 22658920
TI  - Endoscopic closure devices.

PMID- 22658921
TI  - Sexual dimorphisms in the immune system of catechol-O-methyltransferase knockout
      mice.
AB  - The enzyme catechol-O-methyltransferase (COMT) is part of the metabolic pathway
      of 17beta-estradiol, converting 2-hydroxyestradiol to 2-methoxyestradiol. We
      recently showed that administration of the COMT product 2-methoxyestradiol has
      anti-inflammatory and anti-osteoporotic effects. We have now investigated whether
      COMT affects the immune system, by immunologically phenotyping COMT deficient
      (COMT(-/-)) mice. Immunoglobulin production, T lymphocyte proliferation, NK cell
      cytotoxicity and oxygen radical production were assessed. In male COMT(-/-)-mice,
      the total number of T-, and B-lymphocytes from spleen increased but the T-cell
      proliferative response decreased. The NK cell population shifted toward less
      mature cells, leaving cytotoxic capacity unaffected. In COMT(-/-)-females, a
      higher frequency of neutrophils was found but the oxygen radical production was
      unaltered. In conclusion, only minor changes of the immune system were seen in
      COMT deficient mice, and the changes were usually seen in males. This study
      provides clues into how COMT activity, and hence gender differences, affects the
      immune system.

PMID- 22658922
TI  - Effect of granulocyte colony-stimulating factor mobilization on the expression
      patterns, clonality and signal transduction of TRAV and TRBV repertoire.
AB  - The immune modulatory effect of granulocyte colony-stimulating factor (G-CSF) on
      T cells resulted in an unexpected low incidence of graft-versus-host disease
      (GVHD) in allogeneic peripheral blood stem cell transplantation (allo-PBSCT).
      Recently, alphabeta(+) T cells are identified as the primary effector cells for
      GVHD. However, whether G-CSF could influence the repertoire of alphabeta(+) T
      cells (TRAV and TRBV repertoire) and CD3 genes remains unclear. To further
      characterize this feature, we investigated the effect of G-CSF mobilization on
      the T cell receptors (TCR) of alphabeta(+) T cells (TRAV and TRBV repertoire) and
      CD3 genes, as well as the association between the changes of TCR repertoire and
      GVHD in patients undergoing G-CSF mobilized allo-PBSCT. We found that G-CSF
      mobilization had an effect on the expression patterns, clonality and signal
      transduction of TRAV and TRBV repertoire. This alteration might play a role in
      mediating GVHD in G-CSF mobilized allo-PBSCT.

PMID- 22658923
TI  - From genes to social communication: molecular sensing by the vomeronasal organ.
AB  - The ability to distinguish molecular cues emitted by other individuals is a
      fundamental feature of social interactions such as finding and identifying a
      mate, establishing social hierarchies, and initiating interspecies defensive
      behaviors. In rodents, this ability involves the vomeronasal organ (VNO), a
      distinct chemoreceptive structure that is part of the olfactory system. Recent
      insights have led to unprecedented progress in identifying ligand and receptor
      families underlying vomeronasal recognition, characterizing the behavioral
      consequences caused by VNO activation, and defining higher neural circuits
      underlying the initiation of instinctive behaviors such as aggression. Here, we
      review such findings and discuss future areas for investigation, including large
      scale mapping studies, immune system-VNO interactions, in vivo recording of
      neural activity, and optogenetic alteration of sexual and social behaviors.

PMID- 22658925
TI  - Impact of heating method on the flocculation process using thermosensitive
      polymer.
AB  - The impact of suspension heating method on the flocculation process using
      thermosensitive polymer is reported in this paper. In experiments a model
      suspension of chalk in RO water (purified by Reverse Osmosis) was destabilized
      using a copolymer of N-isopropylacrylamide (NIPAM) and cationic diallyldimethyl
      ammonium chloride (DADMAC). The measurements were made using a laboratory setup
      consisting of a mixing tank with four baffles, Rushton turbine, laser particle
      sizer Analysette 22 by Fritsch and a system of pump and thermostating devices.
      Two different modes of heating were used. In the first case the temperature of
      the system was gently raised above the Lower Critical Solution Temperature (LCST)
      using an electrical heater placed inside the tank, while in the second case the
      system temperature was rapidly raised by an injection of hot water directly into
      the tank. It was proven that heating method as well as the polymer concentration
      was crucial to the shape and size of created flocs.

PMID- 22658926
TI  - Better referral of soft tissue sarcoma.

PMID- 22658924
TI  - Functional network dysfunction in anxiety and anxiety disorders.
AB  - A recent paradigm shift in systems neuroscience is the division of the human
      brain into functional networks. Functional networks are collections of brain
      regions with strongly correlated activity both at rest and during cognitive
      tasks, and each network is believed to implement a different aspect of cognition.
      We propose here that anxiety disorders and high trait anxiety are associated with
      a particular pattern of functional network dysfunction: increased functioning of
      the cingulo-opercular and ventral attention networks as well as decreased
      functioning of the fronto-parietal and default mode networks. This functional
      network model can be used to differentiate the pathology of anxiety disorders
      from other psychiatric illnesses such as major depression and provides targets
      for novel treatment strategies.

PMID- 22658928
TI  - Immune markers and correlates of protection for vaccine induced immune responses.
AB  - Vaccines have been a major innovation in the history of mankind and still have
      the potential to address the challenges posed by chronic intracellular infections
      including tuberculosis, HIV and malaria which are leading causes of high
      morbidity and mortality across the world. Markers of an appropriate humoral
      response currently remain the best validated correlates of protective immunity
      after vaccination. Despite advancements in the field of immunology over the past
      few decades currently there are, however, no sufficiently validated immune
      correlates of vaccine induced protection against chronic infections in neither
      human nor veterinary medicine. Technological and conceptual advancements within
      cell-mediated immunology have led to a number of new immunological read-outs with
      the potential to emerge as correlates of vaccine induced protection. For T(H)1
      type responses, antigen-specific production of interferon-gamma (IFN-gamma) has
      been promoted as a quantitative marker of protective cell-mediated immune
      responses over the past couple of decades. More recently, however, evidence from
      several infections has pointed towards the quality of the immune response,
      measured through increased levels of antigen-specific polyfunctional T cells
      capable of producing a triad of relevant cytokines, as a better correlate of
      sustained protective immunity against this type of infections. Also the
      possibilities to measure antigen-specific cytotoxic T cells (CTL) during
      infection or in response to vaccination, through recombinant major
      histocompatibility complex (MHC) class I tetramers loaded with relevant peptides,
      has opened a new vista to include CTL responses in the evaluation of protective
      immune responses. Here, we review different immune markers and new candidates for
      correlates of a protective vaccine induced immune response against chronic
      infections and how successful they have been in defining the protective immunity
      in human and veterinary medicine.

PMID- 22658927
TI  - Passive immunization with a monoclonal IgM antibody specific for Strongyloides
      ratti HSP60 protects mice against challenge infection.
AB  - It is estimated that 30-100 million people are infected with the pathogenic
      nematode Strongyloides stercoralis worldwide but parasite control is still based
      on anti-helminthic treatment. To develop protective vaccination strategies, we
      use the murine model of Strongyloides ratti infection. We have shown recently
      that vaccination with alum-precipitated, but not with native or CFA-emulsified S.
      ratti heat shock protein 60 (srHSP60) conferred protection to challenge
      infection. Here we describe the generation of a monoclonal IgM specific for
      srHSP60. Anti-srHSP60 detected human and srHSP60 and stained S. ratti infective
      larvae in vitro. Passive immunization of mice with monoclonal anti-srHSP60 IgM
      led to reduced numbers of migrating larvae in lung and head, reduced numbers of
      parasitic adults in the small intestine and reduced larval output upon S. ratti
      challenge infection. Taken together, our findings highlight the relevance of
      srHSP60 as vaccine candidate for the induction of antibody-mediated protection
      against Strongyloides infection.

PMID- 22658929
TI  - Evolution of immune response against Neisseria meningitidis B:14:P1.7,16 before
      and after the outer membrane vesicle vaccine MenBvac.
AB  - A meningococcal B:14:P1.7,16 outbreak in Normandy (France) was recently
      controlled using MenBvac, an outer membrane vesicle vaccine previously designed
      against the B:15:P1.7,16 strain. The further emergence of a new B:14:P1.7,16
      outbreak in another district in Normandy led us to explore immunity against
      B:14:P1.7,16 before and after the MenBvac campaign using a 2+1 (day 0, week 6,
      month 8) schedule. Children (1-5 years) were sampled before, during and up to one
      year after vaccination. Serum bactericidal activity against B:14:P1.7,16 was
      titrated using human complement (hSBA) and immune response was defined by hSBA
      titer >=4 as a surrogate for protection. The percentage of hSBA titer >=4 was
      10.8% before vaccination, raised to 84.1% 6 weeks after the completion of the
      schedule, but declined to 39.7% one year later. This level is lower than the
      targeted 60% level and suggests only short-term persistence of response against
      B:14:P1.7,16 using this schedule.

PMID- 22658930
TI  - Capacity for a global vaccine safety system: the perspective of national
      regulatory authorities.
AB  - Confidence in vaccine safety is critical to national immunization strategies and
      to global public health. To meet the Millenium Development Goals, and buoyed by
      the success of new vaccines produced in developing countries, the World Health
      Organization has been developing a strategy to establish a global system for
      effective vaccine pharmacovigilance in all countries. This paper reports the
      findings of a qualitative survey, conducted for the WHO Global Vaccine Safety
      Blueprint project, on the perspectives of national regulatory authorities
      responsible for vaccine safety in manufacturing and procuring countries. Capacity
      and capabilities of detecting, reporting and responding to adverse events
      following immunization (AEFI), and expectations of minimum capacity necessary for
      vaccine pharmacovigilance were explored. Key barriers to establishing a
      functional national vaccine safety system in developing countries were
      identified. The lack of infrastructure, information technology for stable
      communications and data exchange, and human resources affect vaccine safety
      monitoring in developing countries. A persistent "fear of reporting" in several
      low and middle income countries due to insufficient training and insecure
      employment underlies a perceived lack of political will in many governments for
      vaccine pharmacovigilance. Regulators recommended standardized and
      internationally harmonized safety reporting forms, improved surveillance
      mechanisms, and a global network for access and exchange of safety data
      independent of industry.

PMID- 22658931
TI  - A genome-wide association study of host genetic determinants of the antibody
      response to Anthrax Vaccine Adsorbed.
AB  - Several lines of evidence have supported a host genetic contribution to vaccine
      response, but genome-wide assessments for specific determinants have been sparse.
      Here we describe a genome-wide association study (GWAS) of protective antigen
      specific antibody (AbPA) responses among 726 European-Americans who received
      Anthrax Vaccine Adsorbed (AVA) as part of a clinical trial. After quality
      control, 736,996 SNPs were tested for association with the AbPA response to 3 or
      4 AVA vaccinations given over a 6-month period. No SNP achieved the threshold of
      genome-wide significance (p=5 * 10(-8)), but suggestive associations (p<1 * 10(
      5)) were observed for SNPs in or near the class II region of the major
      histocompatibility complex (MHC), in the promoter region of SPSB1, and adjacent
      to MEX3C. Multivariable regression modeling suggested that much of the
      association signal within the MHC corresponded to previously identified HLA DR-DQ
      haplotypes involving component HLA-DRB1 alleles of *15:01, *01:01, or *01:02. We
      estimated the proportion of additive genetic variance explained by common SNP
      variation for the AbPA response after the 6 month vaccination. This analysis
      indicated a significant, albeit imprecisely estimated, contribution of variation
      tagged by common polymorphisms (p=0.032). Future studies will be required to
      replicate these findings in European Americans and to further elucidate the host
      genetic factors underlying variable immune response to AVA.

PMID- 22658932
TI  - Workforce diversity in outpatient substance abuse treatment: the role of leaders'
      characteristics.
AB  - Although the outpatient substance abuse treatment field has seen an increase in
      referrals of African American and Latino clients, there have been limited changes
      in the diversity of the workforce. This discordance may exacerbate treatment
      disparities experienced by these clients. Program leaders have significant
      influence to leverage resources to develop staff diversity. Analysis of panel
      data from 1995 to 2005 showed that the most significant predictors of diversity
      were the characteristics of leaders. In particular, programs with managers with
      racially and ethnically concordant backgrounds and their education level were
      positively related to the percentage of Latino and African American staff. A high
      percentage of African American staff was positively associated with managers'
      tenure, but inversely related to licensed directors. Diversification of the field
      has increased, yet efforts have not matched increases in client diversity.
      Implications for health care reform legislation seeking to improve cultural
      competence through diversification of the workforce are discussed.

PMID- 22658933
TI  - Moving the issue of renal dietitian staffing forward.
AB  - The day-to-day pragmatic work realities of dietitians who cover dialysis clinics
      are rarely the focus of discussion. This article highlights the points of
      convergence between these realities and the research literature. Focusing on the
      National Kidney Foundation Kidney Disease Outcomes Quality Initiative clinical
      practice guidelines for nutrition and the difficulties encountered with their
      full implementation, a seemingly pervasive problem of limited time is revealed.
      Given the evidence that renal dietitians can positively impact morbidity and
      mortality risks, when protein-energy malnutrition is primarily the byproduct of
      insufficient nutrient intake, it suggests that progress with enhancing the
      nutritional status of patients may be fundamentally contingent on increasing the
      time they have available, through improved staffing.

PMID- 22658934
TI  - Dietary factors and risk of kidney stone: a case-control study in southern China.
AB  - OBJECTIVE: Formation of kidney stones is a multifactorial disease, and diet and
      lifestyle are suggested to contribute remarkably to increased prevalence. The
      population of Guangzhou, China has a high prevalence rate of kidney stones;
      however, its risk factors are still unknown. The aim of this study was to
      investigate the dietary risk factors for kidney stones in southern China. DESIGN:
      A case-control study was carried out. SETTING: This study was carried out at the
      Department of Health Management Center, Guangzhou Nanfang Hospital, China.
      SUBJECTS: This study involved 1,019 newly diagnosed kidney stone patients and 987
      healthy control subjects. INTERVENTION: A questionnaire regarding dietary
      patterns and supplements was used to investigate the risk factors for kidney
      stone formation. MAIN OUTCOME MEASURE: Food intake frequency, beverage and
      alcohol consumption, food supplements, and anthropometry were assessed. RESULTS:
      In the analysis, we found positive associations of kidney stones with consumption
      of grains (odds ratio [OR] = 2.08; 95% confidence interval [CI] = 1.08, 4.02) and
      bean products (OR = 3.50; 95% CI = 1.61, 7.59) in women. The variable "fluid
      drinking" showed a significant protective effect against kidney stones in men (OR
      = 0.57; 95% CI = 0.36, 0.88). Consuming leafy vegetables more than 3 times per
      day was positively associated with stones in both men and women (OR = 2.02; 95%
      CI = 1.04, 3.91 and OR = 3.86; 95% CI = 1.48, 10.04, respectively). Other dietary
      factors, dietary supplements, and specific food were not related to kidney stone
      formation in Guangzhou, China. CONCLUSION: The results confirmed that specific
      diet can affect stone formation in the Chinese population, and varied risk
      factors were found for different genders.

PMID- 22658935
TI  - Optical tweezers studies on Notch: single-molecule interaction strength is
      independent of ligand endocytosis.
AB  - Notch signaling controls diverse cellular processes critical to development and
      disease. Cell surface ligands bind Notch on neighboring cells but require
      endocytosis to activate signaling. The role ligand endocytosis plays in Notch
      activation has not been established. Here we integrate optical tweezers with cell
      biological and biochemical methods to test the prevailing model that ligand
      endocytosis facilitates recycling to enhance ligand interactions with Notch
      necessary to trigger signaling. Specifically, single-molecule measurements
      indicate that interference of ligand endocytosis and/or recycling does not alter
      the force required to rupture bonds formed between cells expressing the Notch
      ligand Delta-like1 (Dll1) and laser-trapped Notch1 beads. Together, our analyses
      eliminate roles for ligand endocytosis and recycling in Dll1-Notch1 interactions
      and indicate that recycling indirectly affects signaling by regulating the
      accumulation of cell surface ligand. Importantly, our study demonstrates the
      utility of optical tweezers to test a role for ligand endocytosis in generating
      cell-mediated mechanical force.

PMID- 22658936
TI  - Notch ligand endocytosis generates mechanical pulling force dependent on dynamin,
      epsins, and actin.
AB  - Notch signaling induced by cell surface ligands is critical to development and
      maintenance of many eukaryotic organisms. Notch and its ligands are integral
      membrane proteins that facilitate direct cell-cell interactions to activate Notch
      proteolysis and release the intracellular domain that directs Notch-specific
      cellular responses. Genetic studies suggest that Notch ligands require
      endocytosis, ubiquitylation, and epsin endocytic adaptors to activate signaling,
      but the exact role of ligand endocytosis remains unresolved. Here we characterize
      a molecularly distinct mode of clathrin-mediated endocytosis requiring ligand
      ubiquitylation, epsins, and actin for ligand cells to activate signaling in Notch
      cells. Using a cell-bead optical tweezers system, we obtained evidence for cell
      mediated mechanical force dependent on this distinct mode of ligand endocytosis.
      We propose that the mechanical pulling force produced by endocytosis of Notch
      bound ligand drives conformational changes in Notch that permit activating
      proteolysis.

PMID- 22658937
TI  - Central leptin and insulin administration modulates serum cytokine- and
      lipoprotein-related markers.
AB  - In most obese patients there is an inflammatory state characterized by lipid
      abnormalities, hyperleptinemia and hyperinsulinemia. OBJECTIVE: The objective was
      to identify mechanisms involved in leptin's role in the attenuation of the
      response to insulin using a proteomic approach. MATERIAL/METHODS: We studied the
      serum proteomic profile of rats treated by central leptin infusion followed by an
      injection of insulin. We analyzed the relationship between these proteins and
      serum cytokine and apolipoprotein levels. RESULTS: Out of 81 protein spots,
      intensity differences were found in 11, corresponding to 5 proteins: three
      isoforms of alpha1 macroglobulin; three of haptoglobin and serum amyloid P
      component-precursor. All of these are acute-phase proteins involved in
      inflammation and are correlated with cytokine levels. Additionally, two
      apolipoprotein E and two apolipoprotein A1 isoforms were identified and were
      found to correlate with LDL and HDL. CONCLUSIONS: Our results indicate that
      increased leptin and insulin levels change these circulating proteins, thus
      promoting systemic inflammation and changing lipid metabolism.

PMID- 22658938
TI  - Impact of dietary fat quantity and quality on skeletal muscle fatty acid
      metabolism in subjects with the metabolic syndrome.
AB  - Insulin resistance is characterized by disturbances in lipid metabolism in
      skeletal muscle. Our aim was to investigate whether gene expression and fatty
      acid (FA) profile of skeletal muscle lipids are affected by diets differing in
      fat quantity and quality in subjects with the metabolic syndrome (MetS) and
      varying degrees of insulin sensitivity. 84 subjects (age 57.3+/-0.9 y, BMI 30.9+/
      0.4 kg/m(2), 42 M/42 F) were randomly assigned to one of four iso-energetic
      diets: high-SFA (HSFA); high-MUFA (HMUFA) or two low-fat, high-complex
      carbohydrate diets, supplemented with 1.24 g/day of long-chain n-3 PUFA (LFHCCn
      3) or control oil (LFHCC) for 12 weeks. In a subgroup of men (n=26), muscle TAG,
      DAG, FFA and phospholipid contents were determined including their fractional
      synthetic rate (FSR) and FA composition at fasting and 4h after consumption of a
      high-fat mixed-meal, both pre- and post-intervention. Genes involved in
      lipogenesis were downregulated after HMUFA (mean fold change -1.3) and after
      LFHCCn-3 (fold change -1.7) in insulin resistant subjects (< median of (S(I))),
      whereas in insulin sensitive subjects (>median of insulin sensitivity) the
      opposite effect was shown (fold change +1.6 for both diets). HMUFA diet tended to
      decrease FSR in TAG (P=.055) and DAG (P=.066), whereas the LFHCCn-3 diet reduced
      TAG content (P=.032). In conclusion, HMUFA and LFHCCn-3 diets reduced the
      expression of the lipogenic genes in skeletal muscle of insulin resistant
      subjects, whilst HMUFA reduced the fractional synthesis rate of DAG and TAG and
      LFHCC n-3 the TAG content. Our data indicate that these diets may reduce muscle
      fat accumulation by affecting the balance between FA synthesis, storage and
      oxidation.

PMID- 22658939
TI  - Bacterial signaling systems as platforms for rational design of new generations
      of biosensors.
AB  - Bacterial signal-responsive regulatory circuits have been employed as platform to
      design and construct whole-cell bacterial biosensors for reporting toxicity. A
      new generation of biosensors with improved performance and a wide application
      range has emerged after the application of synthetic biology concepts to
      biosensor design. Site-directed mutagenesis, directed evolution and domain
      swapping were applied to upgrade signal detection or to create novel sensor
      modules. Rewiring of the genetic circuits allows improving the determinations and
      reduces the heterogeneity of the response between individual reporter cells.
      Moreover, the assembly of natural or engineered modules to biosensor platforms
      provides innovative outputs, expanding the range of application of these devises,
      from monitoring toxics and bioremediation to killing targeted cells.

PMID- 22658940
TI  - Isolation and identification of an anti-algal compound from Artemisia annua and
      mechanisms of inhibitory effect on algae.
AB  - The goals of this work were to isolate and identify an anti-algal compound from
      extracts of Artemisia annua and study its mode of action on Microcystis
      aeruginosa. The anti-algal compound was isolated from the extracts using column
      chromatography and activity-guided fractionation methods. Artemisinin with strong
      anti-algal activity was identified by gas chromatography-mass spectrometry and
      (1)H Nuclear Magnetic Resonance. The EC(50) of artemisinin on M. aeruginosa was
      3.2mg L(-1). Artemisinin decreased the soluble protein content and increased the
      superoxide dismutase activity and ascorbic acid content of M. aeruginosa, but
      exerted no effect on soluble sugar content. The results suggested the mode of
      action of artemisinin on algae may primarily be the increasing level of reactive
      oxygen species in algae cells. The results of our research could aid in the
      development of new anti-algal substances and lead to further study of mechanisms
      of inhibitory effect on algae.

PMID- 22658941
TI  - The structure of the fire fighting foam surfactant Forafac(r)1157 and its
      biological and photolytic transformation products.
AB  - For several decades, perfluorooctane sulfonate (PFOS) has widely been used as a
      fluorinated surfactant in aqueous film forming foams used as hydrocarbon fuel
      fire extinguishers. Due to concerns regarding its environmental persistence and
      toxicological effects, PFOS has recently been replaced by novel fluorinated
      surfactants such as Forafac(r)1157, developed by the DuPont company. The major
      component of Forafac(r)1157 is a 6:2 fluorotelomer sulfonamide alkylbetaine (6:2
      FTAB), and a link between the trade name and the exact chemical structure is
      presented here to the scientific community for the first time. In the present
      work, the structure of the 6:2 FTAB was elucidated by (1)H, (13)C and (19)F
      nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.
      Moreover, its major metabolites from blue mussel (Mytilus edulis) and turbot
      (Scophthalmus maximus) and its photolytic transformation products were
      identified. Contrary to what has earlier been observed for PFOS, the 6:2 FTAB was
      extensively metabolized by blue mussel and turbot exposed to Forafac(r)1157. The
      major metabolite was a deacetylated betaine species, from which mono- and di
      demethylated metabolites also were formed. Another abundant metabolite was the
      6:2 fluorotelomer sulfonamide. In another experiment, Forafac(r)1157 was
      subjected to UV-light induced photolysis. The experimental conditions aimed to
      simulate Arctic conditions and the deacetylated species was again the primary
      transformation product of 6:2 FTAB. A 6:2 fluorotelomer sulfonamide was also
      formed along with a non-identified transformation product. The environmental
      presence of most of the metabolites and transformation products was qualitatively
      demonstrated by analysis of soil samples taken in close proximity to an airport
      fire training facility.

PMID- 22658942
TI  - The use of experimental data and their uncertainty for assessing ozone
      photochemistry in the Eastern Iberian Peninsula.
AB  - Observation-based methods are useful tools to explore the sensitivity of ozone
      concentrations to precursor controls. With the aim of assessing the ozone
      precursor sensitivity in two locations: Paterna (suburban) and Villar del
      Arzobispo (rural) of the Turia river basin in the east of Spain, the
      photochemical indicator O(3)/NO(y) and the Extent-of-Reaction (EOR) parameter
      have been calculated from field measurements. In Paterna, the O(3)/NO(y) ratio
      varied from 0 to 13 with an average value of 5.1 (SD 3.2), whereas the averaged
      value for the EOR was 0.43 (SD 0.14). In Villar del Arzobispo, the O(3)/NO(y)
      ratio changed from 5 to 30 with a mean value of 13.6 (SD 4.7) and the EOR gave an
      averaged value of 0.72 (SD 0.11). The results show two different patterns of
      ozone production as a function of the location. The suburban area shows a VOC
      sensitive regime whereas the rural one shows a transition regime close to NO(x)
      sensitive conditions. No seasonal differences in these regimes are observed along
      the monitoring campaigns. Finally, an analysis of the influence of the
      measurement quality of NO(y), NO(x) and O(3) on the uncertainty of the O(3)/NO(y)
      ratio and the EOR was performed showing that the uncertainty of O(3)/NO(y) is not
      dependent on either its value or the individual values of O(3) and NO(y) but just
      on the quality of O(3) and NO(y) measurements. The maximum uncertainty is 26% as
      long as the combined uncertainties of O(3) and NO(y) remain below the 7.5%. The
      case of the EOR is different and its uncertainty depends on both the value of the
      EOR parameter and the individual concentration values of NO(y) and NO(x). The
      uncertainty of the EOR estimation can be very high (>200%) if the combined
      uncertainties of both NO(y) and NO(x) are high (>7.5%), or especially, if
      u(NO(y)) and u(NO(x)) differ considerably from each other (>3.5%).

PMID- 22658943
TI  - The exposition of a calcareous Mediterranean soil to toxic concentrations of Cr,
      Cd and Pb produces changes in the microbiota mainly related to differential metal
      bioavailability.
AB  - The involvement of the bacterial community of an agricultural Mediterranean
      calcareous soil in relation to several heavy metals has been studied in
      microcosms under controlled laboratory conditions. Soil samples were artificially
      polluted with Cr(VI), Cd(II) and Pb(II) at concentrations ranging from 0.1 to
      5000 mg kg(-1) and incubated along 28 d. The lowest concentrations with
      significant effects in soil respirometry were 10 mg kg(-1) Cr and 1000 mg kg(-1)
      Cd and Pb. However, only treatments showing more than 40% inhibition of
      respirometric activity led to significant changes in bacterial composition, as
      indicated by PCR-DGGE analyses. Presumable Cr- and Cd-resistant bacteria were
      detected in polluted microcosms, but development of the microbiota was severely
      impaired at the highest amendments of both metals. Results also showed that
      bioavailability is an important factor determining the impact of the heavy metals
      assayed, and even an inverted potential toxicity ranking could be achieved if
      their soluble fraction is considered instead of the total concentration.
      Moreover, multiresistant bacteria were isolated from Cr-polluted soil microcosms,
      some of them showing the capacity to reduce Cr(VI) concentrations between 26% and
      84% of the initial value. Potentially useful strains for bioremediation were
      related to Arthrobacter crystallopoietes, Stenotrophomonas maltophilia and
      several species of Bacillus.

PMID- 22658944
TI  - Chromium speciation in river sediment pore water contaminated by tannery
      effluent.
AB  - Cr(VI) is far more soluble and toxic than Cr(III). Sediment pore water was
      investigated in a river adjacent to the property of a large former tannery, into
      which Cr-contaminated effluent was discharged over a 55-year period, and where
      extremely high Cr concentrations have been found in the sediments. Dialysis
      cells, or peepers, were used to generate depth profiles of Cr concentration in
      sediment pore water. Samples were analyzed for total Cr using inductively coupled
      plasma-mass spectrometry (ICP-MS) and for Cr species using high performance
      liquid chromatography (HPLC)-ICP-MS. The results show an absence of Cr(VI) in all
      samples. Furthermore, incomplete recovery of Cr(VI) added to the samples
      collected at the locations with highest sediment Cr concentrations indicate
      strong reducing conditions at those locations, which are not conducive to the
      presence of Cr(VI).

PMID- 22658945
TI  - Accelerated long-term forgetting (ALF) and transient epileptic amnesia (TEA): two
      cases of epilepsy-related memory disorder.
AB  - Temporal lobe epilepsy (TLE) has long been associated with memory impairment.
      Recently, two specific forms of memory complaint in this population have been
      identified: accelerated long-term forgetting (ALF) and transient epileptic
      amnesia (TEA). This paper presents neuropsychological data (standard
      neuropsychological tests and experimental measures) on two patients who presented
      in the epilepsy clinic with seemingly similar subjective reports of profound
      memory difficulties. This paper illustrates the differences between TEA and ALF.
      Our focus was on measuring long-term forgetting utilizing a novel visual and
      verbal test protocol, with responses elicited via verbal prompts over the
      telephone at intervals up to 30 days. Whereas patient SK had neuropsychological
      test evidence of problems with learning plus ALF at short and long intervals
      without clinical evidence of TEA, patient EB had clinically convincing TEA
      without neuropsychological test evidence of ALF. In particular, SK showed
      accelerated forgetting while EB did not. This detailed case work develops our
      understanding of ALF measurement and demonstrates that ALF and TEA can be
      dissociated.

PMID- 22658946
TI  - Anticonvulsant effects of agomelatine in mice.
AB  - Agomelatine is a potent MT1 and MT2 melatonin receptor agonist and a 5-HT2C
      serotonin receptor antagonist. We analyzed whether agomelatine has anticonvulsant
      properties. The anticonvulsant activity of agomelatine (25, 50 or 75 mg/kg, i.p.)
      was evaluated in mouse models of pentylenetetrazole (PTZ-85 mg/kg, i.p.),
      pilocarpine (400mg/kg, i.p.), picrotoxin (7 mg/kg, i.p.), strychnine (75 mg/kg,
      i.p.) or electroshock-induced convulsions. In the PTZ-induced seizure model,
      agomelatine (at 25 or 50mg/kg) showed a significant increase in latency to
      convulsion, and agomelatine (at 50 or 75 mg/kg) also increased significantly time
      until death. In the pilocarpine-induced seizure model, only agomelatine in high
      doses (75 mg/kg) showed a significant increase in latency to convulsions and in
      time until death. In the strychnine-, electroshock- and picrotoxin-induced
      seizure models, agomelatine caused no significant alterations in latency to
      convulsions and in time until death when compared to controls. Our results
      suggest that agomelatine has anticonvulsant activity shown in PTZ- or pilocarpine
      induced seizure models.

PMID- 22658947
TI  - Sex differences in how erotic and painful stimuli impair inhibitory control.
AB  - Witnessing emotional events such as arousal or pain may impair ongoing cognitive
      processes such as inhibitory control. We found that this may be true only half of
      the time. Erotic images and painful video clips were shown to men and women
      shortly before a stop signal task, which measures cognitive inhibitory control.
      These stimuli impaired inhibitory control only in men and not in women,
      suggesting that emotional stimuli may be processed with different weights
      depending on gender.

PMID- 22658948
TI  - Driving with navigational instructions: Investigating user behaviour and
      performance.
AB  - This paper reports the results of an inter-disciplinary study investigating user
      preferences and performance in relation to spoken in-car route guidance. In-car
      navigation systems are becoming increasingly popular. However, despite large
      amounts of research assessing the presentation of spatial information, and the
      usability and interaction issues surrounding the interfaces, there has been much
      less investigation of the impacts of auditory presentation of route information.
      We addressed this issue using a multi-disciplinary approach to collect both
      qualitative and quantitative data through questionnaires and user experiments.
      Our research identified a user preference for auditory presentation of route
      information, as well as a memory advantage for auditory over visual presentation.
      We also found that simple auditory route instructions could be followed without
      significant interference to a simulated driving task, whereas more complex
      auditory instructions did cause interference. Taken together, this research
      highlights the importance of the design of spoken route guidance instructions in
      minimising the cognitive demands that they impose.

PMID- 22658949
TI  - Exploring the safety implications of young drivers' behavior, attitudes and
      perceptions.
AB  - The present study aims at identifying and quantifying significant factors (i.e.,
      demographic, aberrant driving behavior) associated with young drivers'
      involvement in at-fault crashes or traffic citations at the ages of 16-17 (while
      having the Operational License) and 18-24 years old (while having the Full
      License). A second objective was to investigate the main reason(s) for
      involvement in risky driving behavior by young drivers. The data used for the
      analyses were obtained from a self-reported questionnaire survey carried out
      among 680 young drivers in Central Florida. To achieve these goals, the
      structural equation modeling approach was adopted. The results revealed that
      aggressive violations, in-vehicle distractions and demographic characteristics
      were the significant factors affecting young drivers' involvement in at-fault
      crashes or traffic violations at the age of 16-17. However, in-vehicle
      distractions, attitudes toward speeding and demographic characteristics were the
      significant factors affecting young drivers' crash risk at 18-24. Additionally,
      the majority of participants reported that "running late" is the main reason for
      taking risk while driving (i.e., speeding, accept short gaps, or drive so close
      to the car in front) followed by "racing other cars". Additionally, "exceed speed
      limits" was the main reason for receiving traffic citations at 16-17 and 18-24
      age groups. Practical suggestions on how to reduce crash risk and promote safe
      driving among young drivers are also discussed.

PMID- 22658950
TI  - Auditory detection and localization of approaching vehicles.
AB  - Pedestrians must use a variety of cues when making safe decisions, many of which
      require processing of auditory information. We examined detection and
      localization of approaching vehicles using auditory cues. 50 adults ages 18-49
      were presented with actual sounds of vehicles approaching at 5, 12, 25, and 35
      mph. Three indices were of interest: the distance at which vehicles were
      detected, participants' decision regarding the direction from which vehicles were
      approaching, and their determination of the vehicles' arrival at their location.
      Participants more easily detected vehicles moving at higher speeds and vehicles
      approaching from the right. Determination of the direction of approach reached
      90% accuracy or better when vehicles were traveling at, or greater than, 12 mph,
      and were more approaching from the right. Determination of vehicle arrival
      deteriorated significantly as speeds increased. Implications of the use of
      auditory cues in pedestrian settings, and future directions, are discussed.

PMID- 22658951
TI  - Ferromagnetic germanide in Ge nanowire transistors for spintronics application.
AB  - To explore spintronics applications for Ge nanowire heterostructures formed by
      thermal annealing, it is critical to develop a ferromagnetic germanide with high
      Curie temperature and take advantage of the high-quality interface between Ge and
      the formed ferromagnetic germanide. In this work, we report, for the first time,
      the formation and characterization of Mn(5)Ge(3)/Ge/Mn(5)Ge(3) nanowire
      transistors, in which the room-temperature ferromagnetic germanide was found
      through the solid-state reaction between a single-crystalline Ge nanowire and Mn
      contact pads upon thermal annealing. The atomically clean interface between
      Mn(5)Ge(3) and Ge with a relatively small lattice mismatch of 10.6% indicates
      that Mn(5)Ge(3) is a high-quality ferromagnetic contact to Ge. Temperature
      dependent I-V measurements on the Mn(5)Ge(3)/Ge/Mn(5)Ge(3) nanowire
      heterostructure reveal a Schottky barrier height of 0.25 eV for the Mn(5)Ge(3)
      contact to p-type Ge. The Ge nanowire field-effect transistors built on the
      Mn(5)Ge(3)/Ge/Mn(5)Ge(3) heterostructure exhibit a high-performance p-type
      behavior with a current on/off ratio close to 10(5), and a hole mobility of 150
      200 cm(2)/(V s). Temperature-dependent resistance of a fully germanided
      Mn(5)Ge(3) nanowire shows a clear transition behavior near the Curie temperature
      of Mn(5)Ge(3) at about 300 K. Our findings of the high-quality room-temperature
      ferromagnetic Mn(5)Ge(3) contact represent a promising step toward electrical
      spin injection into Ge nanowires and thus the realization of high-efficiency
      spintronic devices for room-temperature applications.

PMID- 22658952
TI  - The complex regulation of human glud1 and glud2 glutamate dehydrogenases and its
      implications in nerve tissue biology.
AB  - Mammalian glutamate dehydrogenase (GDH) is a housekeeping mitochondrial enzyme
      (hGDH1 in the human) that catalyses the reversible inter-conversion of glutamate
      to alpha-ketoglutarate and ammonia, thus interconnecting amino acid and
      carbohydrate metabolism. It displays an energy sensing mechanism, which permits
      enzyme activation under low cellular energy states. As GDH is at the crossroads
      of important metabolic pathways, a tight control of its activity is essential.
      Indeed, to fulfill its role in metabolism and cellular energetics, mammalian GDH
      has evolved into a highly regulated enzyme subject to allosteric modulation by
      diverse compounds. The recent emergence (<23 million years ago) in apes and
      humans of a hGDH2 isoenzyme with distinct regulatory properties, as well as, the
      detection of gain-of-function variants in hGDH1 and hGDH2 that affect the nervous
      system, have introduced additional complexities. The properties of the two highly
      homologous human GDHs were studied using purified recombinant hGDH1 and hGDH2
      obtained by expression of the corresponding cDNAs in Sf21 cells. Results showed
      that, in contrast to hGDH1 that maintains substantial basal activity (35-40% of
      its maximal capacity), hGDH2 displays low basal activity (3-8% of maximal) that
      is remarkably responsive to activation by rising levels of ADP and/or l-leucine.
      This is primarily due to the Arg443Ser evolutionary change, which also made hGDH2
      markedly sensitive to estrogens and neuroleptic drugs. In contrast to hGDH1,
      which is subject to potent GTP inhibition, hGDH2 has dissociated its function
      from this energy switch, being able to metabolize glutamate even when the Krebs
      cycle generates GTP levels sufficient to inactivate the housekeeping hGDH1. Our
      data also show that spermidine, a polyamine thought to reduce oxidative stress
      and to prolong survival, and EGCG, a green tea polyphenol, inhibit hGDH2 at lower
      concentrations than hGDH1. The implications of these findings in nerve tissue
      biology are discussed.

PMID- 22658953
TI  - Preconception women's health and pediatrics: an opportunity to address infant
      mortality and family health.

PMID- 22658954
TI  - The SEEK model of pediatric primary care: can child maltreatment be prevented in
      a low-risk population?
AB  - OBJECTIVE: To examine the effectiveness of the Safe Environment for Every Kid
      (SEEK) model of enhanced pediatric primary care to help reduce child maltreatment
      in a relatively low-risk population. METHODS: A total of 18 pediatric practices
      were assigned to intervention or control groups, and 1119 mothers of children
      ages 0 to 5 years were recruited to help evaluate SEEK by completing assessments
      initially and after 6 and 12 months. Children's medical records and Child
      Protective Services data were reviewed. The SEEK model included training health
      professionals to address targeted risk factors (eg, maternal depression), the
      Parent Screening Questionnaire, parent handouts, and a social worker.
      Maltreatment was assessed 3 ways: 1) maternal self-report, 2) children's medical
      records, and 3) Child Protective Services reports. RESULTS: In the initial and 12
      month assessments, SEEK mothers reported less Psychological Aggression than
      controls (initial effect size = -0.16, 95% confidence interval [95% CI] -0.27, 
      0.05, P = .006; 12-month effect size = -0.12, 95% CI -0.24, -0.002, P = .047).
      Similarly, SEEK mothers reported fewer Minor Physical Assaults than controls
      (initial effect size = -0.16, 95% CI -0.29, -0.03, P = .019; 12-month effect size
      = -0.14, 95% CI -0.28, -0.005, P = .043). There were trends in the same positive
      direction at 6 months, albeit not statistically significant. There were few
      instances of maltreatment documented in the medical records and few Child
      Protective Services reports. CONCLUSIONS: The SEEK model was associated with
      reduced maternal Psychological Aggression and Minor Physical Assaults. Although
      such experiences may not be reported to protective services, ample evidence
      indicates their potential harm. SEEK offers a promising and practical enhancement
      of pediatric primary care.

PMID- 22658955
TI  - Sound presentation during different respiration phases alters the sound-induced
      vasoconstriction mediated by the sympathetic nerve.
AB  - The sympathetic orienting response induced by sound has been widely studied and
      utilized as an index of sound-induced emotions and other mental phenomena. Since
      sympathetic activity has its own oscillation that is synchronized with the
      respiration rhythm (sympatho-respiratory coupling), it is possible that the sound
      induced orienting response of sympathetic activity varies depending on the
      respiration phase. In this study, the sound presentations were timed to coincide
      with the onset of inspiration or expiration. 10 experimental sounds were
      presented to 12 males aged 21-35 years. Respiration was monitored with an elastic
      chest band. Vasoconstriction at a finger was measured with laser Doppler
      flowmetry as a sympathetic orienting response. We found that the sound-induced
      vasoconstriction was larger for sounds presented in the inspiration phase than
      for those presented in the expiration phase, suggesting that the respiration
      network-derived sympathetic tone works as a gate for the sound-induced
      sympathetic tone.

PMID- 22658957
TI  - Molecular basis of antibody mediated immunity against Ehrlichia chaffeensis
      involves species-specific linear epitopes in tandem repeat proteins.
AB  - Humoral immune mechanisms are an important component of protective immunity to
      Ehrlichia species. However, the molecular basis of antibody mediated immunity is
      not completely defined, and the role of most molecularly characterized major
      immunoreactive proteins is unknown. In previous studies, we mapped major species
      specific continuous epitopes in three surface exposed and secreted tandem repeat
      proteins (TRP32, TRP47 and TRP120). In this study, we report that protection is
      provided by antibodies against these molecularly defined TRP epitopes using in
      vitro and in vivo models. Protection was demonstrated in vitro after prophylactic
      and therapeutic administration of epitope-specific anti-TRP antibodies,
      suggesting that the protective mechanisms involve extracellular and intracellular
      antibody-mediated effects. In vivo passive transfer of individual epitope
      specific TRP sera significantly reduced the ehrlichial load and splenomegaly, and
      protected mice against lethal infection. Moreover, the combination of antibodies
      to all three TRPs provided enhanced reduction in ehrlichial load similar to that
      of Ehrlichia chaffeensis immune sera. IgG1 was the predominant antibody isotype
      in the epitope-specific TRP mouse sera. These results demonstrate that antibodies
      against linear epitopes in TRP32, TRP47 and TRP120 are protective during E.
      chaffeensis infection and involves extracellular and intracellular antibody
      mediated mechanisms.

PMID- 22658956
TI  - Tissue inducible Lifeact expression allows visualization of actin dynamics in
      vivo and ex vivo.
AB  - We describe here the development and characterization of a conditionally
      inducible mouse model expressing Lifeact-GFP, a peptide that reports the dynamics
      of filamentous actin. We have used this model to study platelets, megakaryocytes
      and melanoblasts and we provide evidence that Lifeact-GFP is a useful reporter in
      these cell types ex vivo. In the case of platelets and megakaryocytes, these
      cells are not transfectable by traditional methods, so conditional activation of
      Lifeact allows the study of actin dynamics in these cells live. We studied
      melanoblasts in native skin explants from embryos, allowing the visualization of
      live actin dynamics during cytokinesis and migration. Our study revealed that
      melanoblasts lacking the small GTPase Rac1 show a delay in the formation of new
      pseudopodia following cytokinesis that accounts for the previously reported
      cytokinesis delay in these cells. Thus, through use of this mouse model, we were
      able to gain insights into the actin dynamics of cells that could only previously
      be studied using fixed specimens or following isolation from their native tissue
      environment.

PMID- 22658958
TI  - Multimodality imaging in the preoperative diagnosis of lipomatous hypertrophy.

PMID- 22658959
TI  - Nano RNA aptamer wire for analysis of vitamin B12.
AB  - A simple and stable RNA aptamer-based colorimetric sensor for the detection of
      vitamin B12 using gold nanoparticles (AuNPs) has been proposed. Vitamin B12
      belongs to the B vitamin group and prevents pernicious anemia, which is caused by
      vitamin B12 deficiency. A highly stable RNA aptamer that binds to vitamin B12 was
      employed by structural modification of 2'-hydroxyl group of ribose to 2'-flouro
      in all pyrimidines indicated in lowercase in 35-mer aptamer (5' GGA Acc GGu GcG
      cAu AAc cAc cuc AGu GcG AGc AA 3'). Aggregation of AuNPs was specifically induced
      by desorption of the vitamin B12 binding RNA aptamer from the surface of AuNPs as
      a result of the aptamer-target interaction, leading to the color change from red
      to purple. The level of detection of vitamin B12 was 0.1 MUg/ml by successful
      optimization of the amount of the aptamer, AuNPs, salts, and stability of the
      aptamer. Analysis of vitamin B12 was carried out, and the observed recovery was
      92 to 95.3% with a relative standard deviation in the range of 2.08 to 8.27%. The
      results obtained were compared with those of the ultraviolet-visible (UV-vis)
      spectrometry method. This colorimetric aptasensor is advantageous for on-site
      detection with the naked eye.

PMID- 22658960
TI  - Fluorescence polarization assay for inhibitors of the kinase domain of receptor
      interacting protein 1.
AB  - Necrotic cell death is prevalent in many different pathological disease states
      and in traumatic injury. Necroptosis is a form of necrosis that stems from
      specific signaling pathways, with the key regulator being receptor interacting
      protein 1 (RIP1), a serine/threonine kinase. Specific inhibitors of RIP1, termed
      necrostatins, are potent inhibitors of necroptosis. Necrostatins are structurally
      distinct from one another yet still possess the ability to inhibit RIP1 kinase
      activity. To further understand the differences in the binding of the various
      necrostatins to RIP1 and to develop a robust high-throughput screening (HTS)
      assay, which can be used to identify new classes of RIP1 inhibitors, we
      synthesized fluorescein derivatives of Necrostatin-1 (Nec-1) and Nec-3. These
      compounds were used to establish a fluorescence polarization (FP) assay to
      directly measure the binding of necrostatins to RIP1 kinase. The fluorescein
      labeled compounds are well suited for HTS because the assays have a dimethyl
      sulfoxide (DMSO) tolerance up to 5% and Z' scores of 0.62 (fluorescein-Nec-1) and
      0.57 (fluorescein-Nec-3). In addition, results obtained from the FP assays and
      ligand docking studies provide insights into the putative binding sites of Nec-1,
      Nec-3, and Nec-4.

PMID- 22658961
TI  - Isotopic profiling of 13C-labeled biological samples by two-dimensional
      heteronuclear J-resolved nuclear magnetic resonance spectroscopy.
AB  - The use of two-dimensional heteronuclear J-resolved (2D H-JRES) nuclear magnetic
      resonance (NMR) spectroscopy for fast and reliable measurement of isotopic
      patterns from 13C-enriched compounds resulting from carbon labeling experiments
      was evaluated. Its use with biological samples of increasing complexity showed
      that 2D H-JRES spectroscopy is suitable for high-throughput isotopic profiling of
      any kind of labeled samples. Moreover, the method enabled accurate quantification
      of 13C enrichments and, thus, can be used for metabolic flux analysis. The
      excellent trade-off between reduced experimental time and the number of
      measurable isotopic data makes 2D H-JRES NMR a promising approach for high
      throughput flux analysis of samples of intermediate complexity.

PMID- 22658963
TI  - Biosynthesis and metabolic engineering of palmitoleate production, an important
      contributor to human health and sustainable industry.
AB  - Palmitoleate (cis-Delta9-16:1) shows numerous health benefits such as increased
      cell membrane fluidity, reduced inflammation, protection of the cardiovascular
      system, and inhibition of oncogenesis. Plant oils containing this unusual fatty
      acid can also be sustainable feedstocks for producing industrially important and
      high-demand 1-octene. Vegetable oils rich in palmitoleate are the ideal
      candidates for biodiesel production. Several wild plants are known that can
      synthesize high levels of palmitoleate in seeds. However, low yields and poor
      agronomic characteristics of these plants limit their commercialization.
      Metabolic engineering has been developed to create oilseed crops that accumulate
      high levels of palmitoleate or other unusual fatty acids, and significant
      advances have been made recently in this field, particularly using the model
      plant Arabidopsis as the host. The engineered targets for enhancing palmitoleate
      synthesis include overexpression of Delta9 desaturase from mammals, yeast, fungi,
      and plants, down-regulating KASII, coexpression of an ACP-Delta9 desaturase in
      plastids and CoA-Delta9 desaturase in endoplasmic reticulum (ER), and optimizing
      the metabolic flux into triacylglycerols (TAGs). This review will mainly describe
      the recent progress towards producing palmitoleate in transgenic plants by
      metabolic engineering along with our current understanding of palmitoleate
      biosynthesis and its regulation, as well as highlighting the bottlenecks that
      require additional investigation by combining lipidomics, transgenics and other "
      omics" tools. A brief review of reported health benefits and non-food uses of
      palmitoleate will also be covered.

PMID- 22658965
TI  - [Stereotactic radiotherapy in pediatric indications].
AB  - Stereotactic radiotherapy is a very high precision procedure, which has been
      limited to radiosurgery for a long time. Technological improvements allowed the
      development of radiotherapy in stereotactic conditions, leading to a lot of
      innovations. Previously indicated for cerebral pathologies, this procedure is now
      developed for extracerebral locations. In paediatrics, stereotactic radiotherapy
      is still limited, delivered precociously, due to the possibility of long-term
      late effects that needs to be addressed. This review reports the different useful
      conditions, technical evolutions, and the current validated paediatric
      indications, with differences from adults, and future directions.

PMID- 22658964
TI  - [Usefulness of procalcitonin upon admission to intensive care in the diagnosis
      and prognosis of sepsis].
AB  - OBJECTIVE: To assess the usefulness of procalcitonin (PCT) upon admission to the
      Intensive Care Unit (ICU) in the diagnosis and prognosis of sepsis DESIGN: A 12
      month prospective observational cohort study was carried out SETTING: An 11-bed
      polyvalent ICU Belonging to a University hospital PATIENTS: Fifty patients with
      systemic inflammatory response syndrome (SIRS) were included. The mean age of the
      patients was 51.66 years, and 68% of them were males VARIABLES OF INTEREST: Upon
      admission, the concentration of PCT and C-reactive protein (CRP) was assessed. At
      discharge, the final diagnosis and outcome were reviewed RESULTS: Thirty-six
      patients had sepsis. Mean PCT +/- SD was higher in sepsis than in non-infectious
      SIRS (19.3 +/- 4.9 vs. 0.65 +/- 0.2) ng/ml) (P=.001). PCT had greater
      discriminating power than CRP (AUC 0.932 vs. 0.827). The cut-off value of PCT for
      the diagnosis of sepsis was 0.92 ng/dl, with a sensitivity of 80.56%, specificity
      85.71%, positive predictive value 93.55% and negative predictive value 63.16%,
      LR+ 5.64 and LR- 0.23. Mortality was higher in patients with sepsis (52.78% vs.
      21.43%) (P=.039). Mean PCT +/- SD upon admission among survivors and deceased
      patients with sepsis was 18.7 +/- 6.7 and 19.5 +/- 7.5 ng/ml, respectively
      (P=.934). CONCLUSIONS: PCT upon admission to the ICU is useful for the diagnosis
      of sepsis, and is more effective than PCR in this respect. However, it is of no
      help in estimating the short-term prognosis.

PMID- 22658962
TI  - Social and emotional predictors of the tempo of puberty in female rhesus monkeys.
AB  - A cascade of neuroendocrine events regulates the initiation and progression of
      female puberty. However, the factors that determine the timing of these events
      across individuals are still uncertain. While the consequences of puberty on
      subsequent emotional development and adult behavior have received significant
      attention, what is less understood are the social and environmental factors that
      actually alter the initiation and progression of puberty. In order to more fully
      understand what factors influence pubertal timing in females, the present study
      quantified social and emotional behavior; stress physiology; and growth and
      activity measures in juvenile female rhesus monkeys to determine what best
      predicts eventual puberty. Based on previous reports, we hypothesized that
      increased agonistic behavior resulting from subordinate status in their natal
      group, in combination with slowed growth, reduced prosocial behavior, and
      increased emotional reactivity would predict delayed puberty. The analyses were
      restricted to behavioral and physiological measures obtained prior to the onset
      of puberty, defined as menarche. Together, our findings indicate that higher
      rates of aggression but lower rates of submission received from group mates;
      slower weight gain; and greater emotional reactivity, evidenced by higher
      anxiety, distress and appeasing behaviors, and lower cortisol responsivity in
      response to a potentially threatening situation, predicts delayed puberty.
      Together the combination of these variables accounted for 58% of the variance in
      the age of menarche, 71% in age at first ovulation, and 45% in the duration of
      adolescent sterility. While early puberty may be more advantageous for the
      individual from a fertility standpoint, it presents significant health risks,
      including increased risk for a number of estrogen dependent cancers and as well
      as the emergence of mood disorders during adulthood. On the other hand, it is
      possible that increased emotional reactivity associated with delayed puberty
      could persist, increasing the risk for emotional dysregulation to socially
      challenging situations. The data argue for prospective studies that will
      determine how emotional reactivity shown to be important for pubertal timing is
      affected by early social experience and temperament, and how these stress-related
      variables contribute to body weight accumulation, affecting the neuroendocrine
      regulation of puberty.

PMID- 22658966
TI  - Two live attenuated Shigella flexneri 2a strains WRSf2G12 and WRSf2G15: a new
      combination of gene deletions for 2nd generation live attenuated vaccine
      candidates.
AB  - Shigella infections are a major cause of inflammatory diarrhea and dysentery
      worldwide. First-generation virG-based live attenuated Shigella strains have been
      successfully tested in phase I and II clinical trials and are a leading approach
      for Shigella vaccine development. Additional gene deletions in senA, senB and
      msbB2 have been engineered into second-generation virG-based Shigella flexneri 2a
      strains producing WRSf2G12 and WRSf2G15. Both strains harbor a unique combination
      of gene deletions designed to increase the safety of live Shigella vaccines.
      WRSf2G12 and WRSf2G15 are genetically stable and highly attenuated in both cell
      culture and animal models of infection. Ocular immunization of guinea pigs with
      either strain induces robust systemic and mucosal immune responses that protect
      against homologous challenge with wild-type Shigella. The data support further
      evaluation of the second-generation strains in a phase I clinical trial.

PMID- 22658967
TI  - Poor immune response to a standard single dose non-adjuvanted vaccination against
      2009 pandemic H1N1 influenza virus A in the adult and elder hemodialysis
      patients.
AB  - BACKGROUND: Hemodialysis patients have higher risk of mortality and morbidity
      when infected with 2009 pandemic H1N1 (pH1N1/09) virus. Depending on different
      methodologies and criteria, previous studies reported variable response rates to
      adjuvanted vaccines against pH1N1/09 virus in hemodialysis patients, however, the
      efficacy of non-adjuvanted vaccines, which are currently used in many countries
      such as the USA and Asian areas, has not been comprehensively evaluated in
      hemodialysis population before. METHODS: We evaluated the efficacy of a standard
      single 15 MUg-dose of non-adjuvanted monovalent pH1N1/09 vaccine (AdimFlu-S) in
      vaccine-naive 110 hemodialysis and 173 healthy participants. When enrolling, all
      participants had not any clinical symptom or sign suggesting pH1N1/09 infection
      since the index case was identified in Taiwan. Sera from all participants were
      tested by hemagglutination inhibition (HI) and micro-neutralization-ELISA
      (microNT-ELISA) tests before and 21 days after vaccination. The outcome
      parameters were seroconversion rate (>= 4-fold in HI titer with titer >= 1:40),
      seroprotection rate (HI titers >= 1:40), seroresponse rate (>= 4-fold increase in
      HI or microNT-ELISA titer), fold of increase in geometric mean (GM) titers, and
      adverse effects. RESULTS: In method A analyses, we included all participants'
      data in final analyses, and the seroconversion rates and the fold increase of GM
      titer after vaccination were 25.4% and 1.8 in adult (18-60-year olds)
      hemodialysis subgroup, and 23.4% and 1.8 in elder (>60-year olds) hemodialysis
      subgroup based on HI titers, which were all significantly lower than those of the
      corresponding healthy control subgroups. Similar trends were observed based on
      microNT-ELISA titers, further validating the results. Multivariable analysis
      revealed hemoglobin and cholesterol levels were significant predictors for
      seroresponse in hemodialysis patients, suggesting the possible impacts of
      nutrition status and anemia. In method B analyses, we excluded participants with
      pre-vaccination seroprotection (based on HI or microNT-ELISA criteria) in final
      analyses. The response rates in various subgroups from method B analyses were
      also similar as those from method A analyses. No severe adverse effect was noted.
      CONCLUSIONS: According to the European and U.S. criteria, a single 15 MUg-dose of
      non-adjuvanted pH1N1/09 vaccination is safe but ineffective in both adult and
      elder hemodialysis patients. Further studies using multiple doses or higher
      antigen amount are warrant to define the most appropriate regimen.

PMID- 22658968
TI  - Surface plasmon resonance analysis of free IgE in allergic patients receiving
      omalizumab (Xolair).
AB  - The diagnosis of human allergic disease involves an initial clinical history
      based association of allergic symptoms with an allergen exposure. This is
      followed by confirmation of sensitization (IgE antibody positivity) with skin
      test, serology or provocation testing. Once diagnosed, the allergic individual
      can be managed using one or several modalities that involve allergen avoidance,
      pharmacotherapy, allergen immunotherapy and anti-IgE therapy. This report
      examines Law of Mass Action considerations for the design of immunological
      methods which permit the quantification of free (non-Omalizumab bound) IgE in the
      serum of patients receiving anti-IgE therapy. The rationale for and design and
      performance of a surface plasmon resonance assay for the detection of "free" IgE
      (unbound with anti-IgE) is presented as an alternative to microtiter plate based
      ELISAs.

PMID- 22658969
TI  - Cancer therapy and vaccination.
AB  - Cancer remains one of the leading causes of death worldwide, both in developed
      and in developing nations. It may affect people at all ages, even fetuses, but
      the risk for most varieties increases with age. Current therapeutic approaches
      which include surgery, chemotherapy and radiotherapy are associated with adverse
      side effects arising from lack of specificity for tumors. The goal of any
      therapeutic strategy is to impact on the target tumor cells with limited
      detrimental effect to normal cell function. Immunotherapy is cancer specific and
      can target the disease with minimal impact on normal tissues. Cancer vaccines are
      capable of generating an active tumor-specific immune response and serve as an
      ideal treatment due to their specificity for tumor cells and long lasting
      immunological memory that may safeguard against recurrences. Cancer vaccines are
      designed to either prevent (prophylactic) or treat established cancer
      (therapeutic). Identification of tumor-associated antigens (TAAs) and tumor
      specific antigens (TSAs) has led to increased efforts to develop vaccination
      strategies. Vaccines may be composed of whole cells or cell extracts, genetically
      modified tumor cells to express costimulatory molecules, dendritic cells (DCs)
      loaded with TAAs, immunization with soluble proteins or synthetic peptides,
      recombinant viruses or bacteria encoding tumor-associated antigens, and plasmid
      DNA encoding TSAs or TAAs in conjunction with appropriate immunomodulators. All
      of these antitumor vaccination approaches aim to induce specific immunological
      responses and localized to TAAs, destroying tumor cells alone and leaving the
      vast majority of other healthy cells of the body untouched.

PMID- 22658970
TI  - Subcapsular liver hematoma causing cardiac tamponade in HELLP syndrome.
AB  - HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome is an
      obstetric complication with heterogeneous presentation, multisystem involvement
      and variable prognosis, but which usually resolves after delivery. We report a
      case of HELLP syndrome with subcapsular hematoma of the liver causing
      extrapericardial cardiac tamponade. The subcapsular hematoma and cardiac
      tamponade were managed conservatively.

PMID- 22658972
TI  - Intrathecal morphine versus transversus abdominis plane block after cesarean
      delivery.

PMID- 22658973
TI  - Second language experience modulates functional brain network for the native
      language production in bimodal bilinguals.
AB  - The functional brain network of a bilingual's first language (L1) plays a crucial
      role in shaping that of his or her second language (L2). However, it is less
      clear how L2 acquisition changes the functional network of L1 processing in
      bilinguals. In this study, we demonstrate that in bimodal (Chinese spoken-sign)
      bilinguals, the functional network supporting L1 production (spoken language) has
      been reorganized to accommodate the network underlying L2 production (sign
      language). Using functional magnetic resonance imaging (fMRI) and a picture
      naming task, we find greater recruitment of the right supramarginal gyrus (RSMG),
      the right temporal gyrus (RSTG), and the right superior occipital gyrus (RSOG)
      for bilingual speakers versus monolingual speakers during L1 production. In
      addition, our second experiment reveals that these regions reflect either
      automatic activation of L2 (RSOG) or extra cognitive coordination (RSMG and RSTG)
      between both languages during L1 production. The functional connectivity between
      these regions, as well as between other regions that are L1- or L2-specific, is
      enhanced during L1 production in bimodal bilinguals as compared to their
      monolingual peers. These findings suggest that L1 production in bimodal
      bilinguals involves an interaction between L1 and L2, supporting the claim that
      learning a second language does, in fact, change the functional brain network of
      the first language.

PMID- 22658974
TI  - Parietal disruption alters audiovisual binding in the sound-induced flash
      illusion.
AB  - Selective attention and multisensory integration are fundamental to perception,
      but little is known about whether, or under what circumstances, these processes
      interact to shape conscious awareness. Here, we used transcranial magnetic
      stimulation (TMS) to investigate the causal role of attention-related brain
      networks in multisensory integration between visual and auditory stimuli in the
      sound-induced flash illusion. The flash illusion is a widely studied multisensory
      phenomenon in which a single flash of light is falsely perceived as multiple
      flashes in the presence of irrelevant sounds. We investigated the hypothesis that
      extrastriate regions involved in selective attention, specifically within the
      right parietal cortex, exert an influence on the multisensory integrative
      processes that cause the flash illusion. We found that disruption of the right
      angular gyrus, but not of the adjacent supramarginal gyrus or of a sensory
      control site, enhanced participants' veridical perception of the multisensory
      events, thereby reducing their susceptibility to the illusion. Our findings
      suggest that the same parietal networks that normally act to enhance perception
      of attended events also play a role in the binding of auditory and visual stimuli
      in the sound-induced flash illusion.

PMID- 22658975
TI  - EEG microstates of wakefulness and NREM sleep.
AB  - EEG-microstates exploit spatio-temporal EEG features to characterize the
      spontaneous EEG as a sequence of a finite number of quasi-stable scalp potential
      field maps. So far, EEG-microstates have been studied mainly in wakeful rest and
      are thought to correspond to functionally relevant brain-states. Four typical
      microstate maps have been identified and labeled arbitrarily with the letters A,
      B, C and D. We addressed the question whether EEG-microstate features are altered
      in different stages of NREM sleep compared to wakefulness. 32-channel EEG of 32
      subjects in relaxed wakefulness and NREM sleep was analyzed using a clustering
      algorithm, identifying the most dominant amplitude topography maps typical of
      each vigilance state. Fitting back these maps into the sleep-scored EEG resulted
      in a temporal sequence of maps for each sleep stage. All 32 subjects reached
      sleep stage N2, 19 also N3, for at least 1 min and 45 s. As in wakeful rest we
      found four microstate maps to be optimal in all NREM sleep stages. The wake maps
      were highly similar to those described in the literature for wakefulness. The
      sleep stage specific map topographies of N1 and N3 sleep showed a variable but
      overall relatively high degree of spatial correlation to the wake maps (Mean: N1
      92%; N3 87%). The N2 maps were the least similar to wake (mean: 83%). Mean
      duration, total time covered, global explained variance and transition
      probabilities per subject, map and sleep stage were very similar in wake and N1.
      In wake, N1 and N3, microstate map C was most dominant w.r.t. global explained
      variance and temporal presence (ratio total time), whereas in N2 microstate map B
      was most prominent. In N3, the mean duration of all microstate maps increased
      significantly, expressed also as an increase in transition probabilities of all
      maps to themselves in N3. This duration increase was partly--but not entirely-
      explained by the occurrence of slow waves in the EEG. The persistence of exactly
      four main microstate classes in all NREM sleep stages might speak in favor of an
      in principle maintained large scale spatial brain organization from wakeful rest
      to NREM sleep. In N1 and N3 sleep, despite spectral EEG differences, the
      microstate maps and characteristics were surprisingly close to wakefulness. This
      supports the notion that EEG microstates might reflect a large scale resting
      state network architecture similar to preserved fMRI resting state connectivity.
      We speculate that the incisive functional alterations which can be observed
      during the transition to deep sleep might be driven by changes in the level and
      timing of activity within this architecture.

PMID- 22658976
TI  - Segmentation of the C57BL/6J mouse cerebellum in magnetic resonance images.
AB  - The C57BL mouse is the centerpiece of efforts to use gene-targeting technology to
      understand cerebellar pathology, thus creating a need for a detailed magnetic
      resonance imaging (MRI) atlas of the cerebellum of this strain. In this study we
      present a methodology for systematic delineation of the vermal and hemispheric
      lobules of the C57BL/6J mouse cerebellum in magnetic resonance images. We have
      successfully delineated 38 cerebellar and cerebellar-related structures. The
      higher signal-to-noise ratio achieved by group averaging facilitated the
      identification of anatomical structures. In addition, we have calculated average
      region volumes and created probabilistic maps for each structure. The
      segmentation method and the probabilistic maps we have created will provide a
      foundation for future studies of cerebellar disorders using transgenic mouse
      models.

PMID- 22658977
TI  - Clozapine decreases exploratory activity and increases anxiety-like behaviour in
      the Wistar-Kyoto rat but not the spontaneously hypertensive rat model of
      attention-deficit/hyperactivity disorder.
AB  - The spontaneously hypertensive rat (SHR) is the most widely used animal model of
      ADHD. SHR has been found to have increased glutamate-stimulated noradrenaline
      release from varicosities in several brain areas. Besides its effects on dopamine
      D4 receptors, clozapine, an atypical antipsychotic with antagonistic effects on
      alpha(1)-adrenoceptors, may reduce activation of alpha(1)-adrenoceptors in SHR
      and thereby attenuate their hyperactivity. The aims of the study were to
      determine the effect of clozapine (post-natal day (P) 21-P35, 10 mg/kg/day) on
      SHR and Wistar-Kyoto (WKY), SHR's normotensive control, and a standard laboratory
      strain, Sprague Dawley (SD). Rat behaviour was assessed in the open field (P32),
      novel object (P33) and elevated plus maze (P34) tests that measured locomotor and
      anxiety-related behaviour. An in vitro superfusion technique was used to measure
      [(3)H]noradrenaline release in prefrontal cortex (PFC) and hippocampal slices
      (P35 or P36). Clozapine decreased exploratory activity in WKY, consistent with
      antagonism of dopamine D4 and alpha(1)-adrenoceptors reducing the behavioural
      response to novelty. Clozapine also increased anxiety-related behaviour of WKY.
      However, clozapine did not affect SHR, suggesting that genetic predisposition may
      play a role in determining clozapine's behavioural effects. WKY have been shown
      to have higher levels of dopamine D4 receptor expression in the PFC than SHR,
      which may be a reason for their elevated response to clozapine. SHR released more
      [(3)H]noradrenaline from PFC and hippocampal slices in response to glutamate- and
      elevated potassium-stimulation, compared to WKY and SD rats. However clozapine
      treatment did not affect glutamate-, GABA- or depolarization-evoked release of
      [(3)H]noradrenaline.

PMID- 22658978
TI  - Transglutaminase 2 modulates antigen-specific antibody response by suppressing
      Blimp-1 and AID expression of B cells in mice.
AB  - Tansglutaminase 2 (TG2) mediates post-translational modifications of proteins
      that are involved in a variety of biological processes. Previous reports suggest
      an involvement of TG2 in adaptive immune responses. However, little has been
      elucidated in this regard. We explored, in this study, the role of TG2 in humoral
      immune response to keyhole limpet hemocyanin (KLH) using TG2(-/-) C57BL/6 mice.
      After primary and secondary immunization with KLH, the serum titer of the antigen
      specific antibody was higher in the TG2(-/-) mice than in the wild-type mice. Not
      only the amount of the specific antibody was increased, but also the affinity of
      the antibody was estimated as higher in these mice. The TG2(-/-) spleen showed an
      enhanced germinal center response with higher percentages of GL7(+) germinal
      center B cells and B220(low) CD138(high) plasma cells. In addition, germinal
      center B cells from TG2(-/-) mice showed an increased expression of B lymphocyte
      induced maturation protein-1 (Blimp-1) as well as activation-induced cytidine
      deaminase (AID). Our results, in sum, indicate a regulatory role of TG2 in
      humoral immune response to a protein antigen, probably by way of modulating the
      expression level of proteins related to humoral immune reposes.

PMID- 22658979
TI  - PKA and cAMP stimulate proliferation of mouse embryonic stem cells by elevating
      GLUT1 expression mediated by the NF-kappaB and CREB/CBP signaling pathways.
AB  - BACKGROUND: Regulation of glucose transporter (GLUT) expression and activity
      plays a vital role in the supply of glucose to embryonic stem (ES) cells.
      METHODS: To observe the effect of 6-phenyl cyclic monophosphate (cAMP) on glucose
      uptake and cell proliferation, 2-deoxyglucose (2-DG) uptake,
      immunohistochemistry, Western blotting, and immunoprecipitation were carried out.
      RESULTS: Among GLUT isoforms in mouse ES cells, GLUT1 was predominantly expressed
      and 6-phenyl cAMP increased GLUT mRNA levels. Among cAMP agonists, 6-phenyl cAMP
      increased 2-DG uptake more than that of 8-p-chlorophenylthio-2'-O-methyl-cAMP. 6
      Phenyl cAMP increased GLUT1 expression and translocation from the cytosol to the
      plasma membrane. 6-Phenyl cAMP increased 2-DG uptake in a time- and concentration
      dependent manner due to an increase in V(max) but not K(m). 6-Phenyl cAMP
      increased phosphorylation of nuclear factor-kappaB (NF-kappaB) and cAMP response
      element binding (CREB) and expression of the CREB protein (CBP) and transducer of
      regulated CREB activity 2 (TORC2) in sequence. 6-Phenyl cAMP induced complex
      formation of NF-kappaB/CREB/CBP/TORC2, which are involved in the increase of
      gluconeogenic enzyme expression. 6-Phenyl cAMP also increased cell cycle
      regulatory protein expression levels, the proportion of S-phase cells, and proto
      oncogene expression via protein kinase A (PKA)-dependent NF-kappaB signaling.
      Finally, GLUT1 siRNA blocked the 6-phenyl cAMP-induced increase in ES cell
      proliferation. We conclude that PKA stimulated the complex formation of
      CREB/CBP/TORC2 via NF-kappaB, which induced effective coordination of glucose
      uptake as well as proliferation in ES cells. GENERAL SIGNIFICANCE: 6-Phenyl cAMP
      induced PKA activation modified the proliferation, which may be beneficial for
      expanding ES cell use to cell therapy.

PMID- 22658980
TI  - The effects of the co-administration of the alpha1-adrenoreceptor antagonist
      prazosin on the anxiolytic effect of citalopram in conditioned fear stress in the
      rat.
AB  - Several studies have shown that the alpha1-adrenoreceptor is involved in
      controlling extracellular serotonin levels. The administration of the alpha1
      adrenoreceptor antagonist prazosin was shown to decrease extracellular serotonin
      levels in the hippocampus, the prefrontal cortex and the raphe nucleus, while the
      administration of the alpha1-adrenoreceptor agonist cirazoline was shown to
      increase serotonin levels. Furthermore, the elevation of serotonin levels induced
      by the selective serotonin reuptake inhibitor (SSRI) citalopram was attenuated by
      prazosin. Thus, alpha1-adrenoreceptor antagonists may affect SSRI-induced
      increases in extracellular serotonin levels and their antidepressive and
      anxiolytic effects. However, little is known about the influence of alpha1
      adrenoreceptor antagonists on the behavioral pharmacological effects of SSRIs.
      The conditioned fear stress-induced freezing behavior is an animal model of
      anxiety and can detect the anxiolytic effect of SSRIs. To clarify whether an
      alpha1-adrenoreceptor antagonist affects the anxiolytic action of SSRIs, we
      examined the effects of the co-administration of the alpha1-adrenoreceptor
      antagonist prazosin and the SSRI citalopram using the contextual conditioned fear
      stress model. Low-dose prazosin (0.03 mg/kg) significantly attenuated the
      citalopram (3 mg/kg)-induced decrease in conditioned freezing. Moreover, high
      dose (0.5 mg/kg), but not low-dose (0.03 mg/kg), prazosin significantly
      attenuated citalopram (10 mg/kg)-induced decreases in conditioned freezing. These
      drugs did not affect the spontaneous motor activity of the rats. Therefore, these
      results suggest that blocking the alpha1-adrenoreceptor decreases the anxiolytic
      effect of citalopram.

PMID- 22658981
TI  - The reduction of superoxide dismutase activity is associated with the severity of
      neurological soft signs in patients with schizophrenia.
AB  - This study aimed to explore the relationship between antioxidant enzyme
      activities and neurological soft signs (NSS) in a sample of patients with
      schizophrenia. Sixty clinically stable patients with schizophrenia treated mostly
      by first-generation antipsychotics and 30 matched healthy controls were
      recruited. NSS were assessed in two groups by a standardized neurological
      examination (Krebs et al., 2000). The red blood cell (RBC) antioxidant activities
      of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)
      were measured by spectrophotometry. RBC activities of all enzymes studied: SOD,
      GSH-Px and CAT, were significantly lower in the patients compared to control
      group. All NSS scores were significantly higher in the patients compared to
      healthy controls' scores. In the patients, a negative correlation was found
      between RBC SOD activity and NSS total score and motor coordination and motor
      integration sub-scores. The association between low SOD activity as a marker of
      oxidative stress and NSS in schizophrenic patients suggests a common pathological
      process of these abnormalities.

PMID- 22658982
TI  - Association between glycogen synthase kinase-3beta gene polymorphisms and
      attention deficit hyperactivity disorder in Korean children: a preliminary study.
AB  - Glycogen synthase kinase (GSK)-3beta plays a key role in the phosphorylation and
      regulation of metabolic enzymes and many transcription factors. Recent studies
      have suggested the involvement of GSK-3beta in the pathogenesis and treatment
      target of DA-associated neuropsychiatric disorders, which has led to consider GSK
      beta as one of the candidate genes for those disorders. GSK-3beta genes are
      likely to be involved in mechanisms underlying attention deficit hyperactivity
      disorder (ADHD). We investigated the association between -1727A/T and -50T/C SNPs
      of GSK-3beta gene with ADHD. All ADHD subjects completed a comprehensive and
      standardized diagnostic test and psychological evaluation battery, including the
      parents' Korean version of the ADHD Rating Scale-IV (ARS). The genotype and
      allele frequencies of 103 ADHD patients and 173 normal controls were analyzed for
      -1727A/T and -50T/C SNPs of GSK-3beta gene. There were statistically significant
      differences in the genotype distributions of the -1727A/T SNP of GSK-3beta gene
      between the ADHD group and the control group. The frequency of the genotype AT
      was significantly higher in the ADHD patients. Concerning the haplotype, there
      was a significant difference in the A-C haplotype frequency between the two
      samples. However, no differences in either the genotype distribution or in allele
      frequencies of -50C/T were observed between the two samples. In the parents
      version of K-ARS of all subjects, ANCOVA revealed that two subscales and the
      total score were significantly higher in the subjects with AT+TT genotypes than
      those with AA genotype after adjusting for age and gender. The odds ratio for the
      ADHD patients was 1.79, comparing the AT genotype group with the AA genotype
      group. Therefore, genotype AT is associated with a higher risk of ADHD. Our
      results suggest that the -1727A/T SNP of GSK-3beta gene may affect susceptibility
      in ADHD. Further investigation with a larger number of subjects is needed to
      validate this finding.

PMID- 22658983
TI  - Synchronized energy and electron transfer processes in covalently linked CdSe
      squaraine dye-TiO2 light harvesting assembly.
AB  - Manipulation of energy and electron transfer processes in a light harvesting
      assembly is an important criterion to mimic natural photosynthesis. We have now
      succeeded in sequentially assembling CdSe quantum dot (QD) and squaraine dye
      (SQSH) on TiO(2) film and couple energy and electron transfer processes to
      generate photocurrent in a hybrid solar cell. When attached separately, both CdSe
      QDs and SQSH inject electrons into TiO(2) under visible-near-IR irradiation.
      However, CdSe QD if linked to TiO(2) with SQSH linker participates in an energy
      transfer process. The hybrid solar cells prepared with squaraine dye as a linker
      between CdSe QD and TiO(2) exhibited power conversion efficiency of 3.65% and
      good stability during illumination with global AM 1.5 solar condition. Transient
      absorption spectroscopy measurements provided further insight into the energy
      transfer between excited CdSe QD and SQSH (rate constant of 6.7 * 10(10) s(-1))
      and interfacial electron transfer between excited SQSH and TiO(2) (rate constant
      of 1.2 * 10(11) s(-1)). The synergy of covalently linked semiconductor quantum
      dots and near-IR absorbing squaraine dye provides new opportunities to harvest
      photons from selective regions of the solar spectrum in an efficient manner.

PMID- 22658985
TI  - Cancer associated human papillomaviruses.
AB  - A small group of human papillomaviruses (HPVs) cause almost all cervical
      carcinoma and a significant percentage of other anogenital tract and oral
      carcinoma. Another group of HPVs causes non-melanoma skin cancers in genetically
      predisposed or immune suppressed patients upon UV exposure. HPV genome
      replication requires the host cell's DNA synthesis machinery and HPVs encode
      proteins that maintain differentiated epithelial cells in a replication competent
      state. The resulting rewiring of cellular signal transduction circuits triggers
      several innate cellular tumor suppressor responses that HPVs need to inactivate
      in order to establish persistent and/or productive infections. This review
      emphasizes this interplay between virus and the infected host cells and points
      out biological similarities and differences between different groups of HPVs.

PMID- 22658986
TI  - Low nanomolar GABA effects at extrasynaptic alpha4beta1/beta3delta GABA(A)
      receptor subtypes indicate a different binding mode for GABA at these receptors.
AB  - Ionotropic GABA(A) receptors are a highly heterogenous population of receptors
      assembled from a combination of multiple subunits. The aims of this study were to
      characterize the potency of GABA at human recombinant delta-containing
      extrasynaptic GABA(A) receptors expressed in Xenopus oocytes using the two
      electrode voltage clamp technique, and to investigate, using site-directed
      mutagenesis, the molecular determinants for GABA potency at alpha4beta3delta
      GABA(A) receptors. alpha4/delta-Containing GABA(A) receptors displayed high
      sensitivity to GABA, with mid-nanomolar concentrations activating
      alpha4beta1delta (EC50=24 nM) and alpha4beta3delta (EC50=12 nM) receptors. In the
      majority of oocytes expressing alpha4beta3delta subtypes, GABA produced a
      biphasic concentration-response curve, and activated the receptor with low and
      high concentrations (EC50(1)=16 nM; EC50(2)=1.2 MUM). At alpha4beta2delta, GABA
      had low micromolar activity (EC50=1 MUM). An analysis of 10 N-terminal singly
      mutated alpha4beta3delta receptors shows that GABA interacts with amino acids
      different to those reported for alpha1beta2gamma2 GABA(A) receptors. Residues
      Y205 and R207 of the beta3-subunit significantly affected GABA potency, while the
      residue F71 of the alpha4- and the residue Y97 of the beta3-subunit did not
      significantly affect GABA potency. Mutating the residue R218 of the delta
      subunit, equivalent to the GABA binding residue R207 of the beta2-subunit,
      reduced the potency of GABA by 670-fold, suggesting a novel GABA binding site at
      the delta-subunit interface. Taken together, GABA may have different binding
      modes for extrasynaptic delta-containing GABA(A) receptors compared to their
      synaptic counterparts.

PMID- 22658987
TI  - Xiao-Qing-Long-Tang attenuates allergic airway inflammation and remodeling in
      repetitive Dermatogoides pteronyssinus challenged chronic asthmatic mice model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Xiao-Qing-Long-Tang (XQLT) has been used for
      centuries in Asia to effectively treat patients with bronchial asthma. AIM OF THE
      STUDY: We previously found that single and multiple doses of XQLT administered to
      sensitized mice before allergen challenge resulted in suppressed airway hyper
      responsiveness and airway inflammation. In this study we aimed to investigate
      whether XQLT has the potential to attenuate the severity of asthma symptoms, and
      immunomodulatory mechanism of XQLT in a repetitive Dermatogoides pteronyssinus
      (D. pteronyssinus)-challenged chronic asthmatic mice model. MATERIALS AND
      METHODS: BALB/c mice were intratracheally (i.t.) inoculated with five doses of D.
      pteronyssinus (50 MUl, 1mg/ml) and orally administered of XQLT (1 g/kg) at 1-week
      intervals. At three days after the last challenge, mice were sacrificed to
      evaluate airway remodeling, inflammation, lung histological features, and the
      expression profiles of cytokines and various genes. RESULTS: XQLT significantly
      reduced bronchial inflammatory cell infiltration and airway remodeling. It
      inhibited D. pteronyssinus-induced total IgE and D. pteronyssinus-specific IgG1
      in serum, and changed the "T(H)2-bios" in BALF by inhibiting the activation of NF
      kappaB. Collagen assay and Histopathology indicated that XQLT reduced airway
      remodeling in the lung. Simultaneously, the RT-PCR analysis showed that XQLT
      downregulated IL-10, IL-13, RANTES, Eotaxin, and MCP-1 mRNA expression in the
      lung. Moreover, EMSA and immunohistochemistry staining demonstrated that XQLT
      inhibited NF-kappaB expression in the nucleus of bronchial epithelial cells.
      CONCLUSIONS: These results suggest that XQLT exhibits anti-airway inflammatory,
      anti-airway remodeling, and specific immunoregulatory effects in a chronic
      asthmatic mice model.

PMID- 22658989
TI  - Comparative study on oxidative treatments of NAPL containing chlorinated ethanes
      and ethenes using hydrogen peroxide and persulfate in soils.
AB  - The goal of this study was to assess the oxidation of NAPL in soil, 30% of which
      were composed of chlorinated ethanes and ethenes, using catalyzed hydrogen
      peroxide (CHP), activated persulfate (AP), and H(2)O(2)-persulfate (HP) co
      amendment systems. Citrate, a buffer and iron ligand, was amended to the
      treatment system to enhance oxidative treatment. Four activation/catalysis
      methods were employed: (1) oxidant only, (2) oxidant-citrate, (3) oxidant
      iron(II), and (4) oxidant-citrate-iron(II). The NAPL treatment effectiveness was
      the greatest in the CHP reactions, the second in HP, and the third in AP. The
      effective activation and catalysis methods depended on the oxidant types; oxidant
      only for CHP and HP and oxidant-citrate-iron for AP. The treatability trend of
      chlorinated ethanes and ethenes in the soil mixture was as follows:
      trichloroethene > tetrachloroethene > dichloroethane > trichloroethane >
      tetrachloroethane. A significant fraction of persulfate remained in the oxidation
      systems after the 2-day reaction period, especially in the citrate-iron(II) AP.
      In general, oxidation systems that included citrate maintained a post-treatment
      pH in the range of 7-9. A final pH of AP oxidation systems was acidic (pH 2-3),
      where a molar ratio of citrate-iron(II) was less than 1.8 and where no citrate
      was amended.

PMID- 22658988
TI  - Protective effect of Fufang-Liu-Yue-Qing, a traditional Chinese herbal formula,
      on CCl4 induced liver fibrosis in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chinese prescription Fufang-Liu-Yue-Qing (FLYQ)
      has long been employed clinically to treat chronic hepatitis B, and we have
      reported its beneficial effects on liver fibrosis in vitro. The present study was
      investigated to verify protective effects of FLYQ on liver fibrosis in a rat
      model and to investigate the underlying mechanisms which have not been explored
      yet. MATERIALS AND METHODS: Liver fibrosis was established by intragastric
      administration of 2 ml/kg CCl(4) twice a week for 12 weeks. During the
      experiment, the model group received CCl(4) only, and the normal control group
      received an equal volume of saline. Treatment groups received not only CCl(4) for
      12 weeks, but also the corresponding drugs, colchicine (1.00 mg/kg/day) or FLYQ
      (300, 150, 75 mg/kg/day) from 5 to 12 weeks. RESULTS: Analysis experiments showed
      that FLYQ could significantly alleviate liver injury, as indicated by decreasing
      levels of ALT, AST, ALP, GGT, IL-6 and TNF-alpha. Moreover, FLYQ could
      effectively inhibit collagen deposition and reduce the pathological tissue
      damage. Research on mechanism showed that FLYQ was able to markedly reduce lipid
      peroxidation, recruit the anti-oxidative defense system, promote ECM degradation
      by modulating the levels of TIMP-1 and MMP-2, and induce HSC apoptosis by down
      regulating bcl-2 mRNA, as well as inhibit the expressions of alpha-SMA and TGF
      beta(1) proteins. CONCLUSIONS: Our results show that FLYQ is effective in
      attenuating hepatic injury and fibrosis in the CCl(4)-induced rat model, which
      should be developed as a new drug for treatment of liver fibrosis and even
      cirrhosis.

PMID- 22658984
TI  - Speed, sensitivity, and stability of the light response in rod and cone
      photoreceptors: facts and models.
AB  - The light responses of rod and cone photoreceptors in the vertebrate retina are
      quantitatively different, yet extremely stable and reproducible because of the
      extraordinary regulation of the cascade of enzymatic reactions that link photon
      absorption and visual pigment excitation to the gating of cGMP-gated ion channels
      in the outer segment plasma membrane. While the molecular scheme of the
      phototransduction pathway is essentially the same in rods and cones, the enzymes
      and protein regulators that constitute the pathway are distinct. These enzymes
      and regulators can differ in the quantitative features of their functions or in
      concentration if their functions are similar or both can be true. The molecular
      identity and distinct function of the molecules of the transduction cascade in
      rods and cones are summarized. The functional significance of these molecular
      differences is examined with a mathematical model of the signal-transducing
      enzymatic cascade. Constrained by available electrophysiological, biochemical and
      biophysical data, the model simulates photocurrents that match well the
      electrical photoresponses measured in both rods and cones. Using simulation
      computed with the mathematical model, the time course of light-dependent changes
      in enzymatic activities and second messenger concentrations in non-mammalian rods
      and cones are compared side by side.

PMID- 22658990
TI  - Determinants of willingness-to-pay for water pollution abatement: a point and
      interval data payment card application.
AB  - This paper shows a contingent valuation exercise of pollution abatement in remote
      lakes. In addition to estimating the usual interval data model, it applies a
      point and interval statistical approach allowing for uncensored data, left
      censored data, right-censored data and left- and right-censored data to explore
      the determinants of willingness-to-pay in a payment card survey. Results suggest
      that the estimations between models may diverge under certain conditions.

PMID- 22658991
TI  - Simulation-based inexact chance-constrained nonlinear programming for
      eutrophication management in the Xiangxi Bay of Three Gorges Reservoir.
AB  - Although integrated simulation and optimization approaches under stochastic
      uncertainty have been applied to eutrophication management problems, few studies
      are reported in eutrophication control planning where multiple formats of
      uncertainties and nonlinearities are addressed in forms of intervals and
      probabilistic distributions within an integrated framework. Since the impounding
      of Three Gorges Reservoir (TGR), China in 2003, the hydraulic conditions and
      aquatic environment of the Xiangxi Bay (XXB) have changed significantly. The
      resulting emergence of eutrophication and algal blooms leads to its deteriorated
      water quality. The XXB becomes an ideal case study area. Thus, a simulation-based
      inexact chance-constrained nonlinear programming (SICNP) model is developed and
      applied to eutrophication control planning in the XXB of the TGR under
      uncertainties. In the SICNP, the wastewater treatment costs for removing total
      phosphorus (TP) are set as the objective function; effluent discharge standards,
      stream water quality standards and eutrophication control standards are
      considered in the constraints; a steady-state simulation model for phosphorus
      transport and fate is embedded in the environmental standards constraints; the
      interval programming and chance-constrained approaches are integrated to provide
      interval decision variables but also the associated risk levels in violating the
      system constraints. The model results indicate that changes in the violating
      level (q) will result in different strategy distributions at spatial and temporal
      scales; the optimal value of cost objective is from [2.74, 13.41] million RMB to
      [2.25, 13.08] million RMB when q equals from 0.01 to 0.25; the required TP
      treatment efficiency for the Baisha plant is the most stringent, which is
      followed by the Xiakou Town and the Zhaojun Town, while the requirement for the
      Pingyikou cement plant is the least stringent. The model results are useful for
      making optimal policies on eutrophication control planning and water quality
      improvement in the XXB.

PMID- 22658992
TI  - Nitrogen dynamics in soil amended with manures composted in dynamic and static
      systems.
AB  - The main objectives of this study were to evaluate the stability of three
      different composts and to study the N dynamics in soil incubated with the
      composts under laboratory conditions. The composts were produced from sheep
      manure processed by static pile composting (C1) and from cattle and sheep manure
      processed by dynamic pile composting (C2 and C3 respectively). Laboratory
      incubation assays were carried out at 28  degrees C to determine the amount of N
      mineralized and N leached under extreme rainfall conditions in the first 30 days
      after application of doses of each compost equivalent to 170 and 450 kg ha(-1) of
      N. There were no differences in the values of these parameters in samples of the
      composts produced by the static (C1) and dynamic (C3) systems, and both composts
      behaved in the same way when applied to soil. The chemical characteristics of the
      three final composts, the respiration rates and the lack of stimulation of total
      microbial biomass indicated that the composts were stable. However, the final C/N
      ratio was slightly higher in C2 than in C1 and C3 (14 compared with 10 and 11) as
      was the respiration rate of the high dose of C2 indicating that C2 was more
      labile, and thus less stable than C1 and C3. Compost C2 generated the highest N
      mineralization rates after application of different doses (6.5 and 13.1%), as
      well as the highest N supplying potential (54.7 and 36.2%), and thus the highest
      rate of mineral N leaching (16.8 and 16.5 mg L(-1) of NO(3)-N), probably as a
      result of the slight difference in lability. The N release after compost
      application was very low and thus the leaching potential was also low, indicating
      that high doses of mature compost (>170 kg ha(-1) of N) could be applied to soil.

PMID- 22658993
TI  - [Potentially inappropriate medication on admission to a medium-stay unit
      according to STOPP and START criteria].
AB  - INTRODUCTION: In older people some drugs are classified as potentially
      inappropriate and some tools have been developed to help to prescribe correctly,
      such as the "Screening Tool of Older Persons' potentially inappropriate
      Prescriptions" (STOPP) and the "Screening Tool to Alert doctors to the Right
      Treatment" (START) criteria. The aim of this study is to determine the prevalence
      and advice on the usefulness of these criteria in a medium-stay unit of a
      geriatric hospital. MATERIAL AND METHODS: A 6 month prospective cross-sectional
      study was designed. A clinical pharmacist verified the accuracy of the medication
      according to STOPP & START criteria on admission. Treatment discrepancies in the
      previous 3 months were validated with two geriatricians. RESULTS: A total of 134
      patients were included over the 6 months, with a mean age 82.02 years, 70% female
      and an average of 11.38 drugs/patient. We recorded 260 possible drug-related
      problems detected by STOPP & START criteria, and those affected 76% of the
      patients. The most frequent were the group of drugs contraindicated in risk of
      falling patients and the cardiovascular group. We considered 24.36% STOPP
      criteria and 54.41% of START criteria as valid. CONCLUSION: STOPP & START
      criteria are useful tool to detect possible drug-related problems in a medium
      stay unit in a geriatric hospital. However, under common clinical practice
      conditions, its validity may vary depending on the specific features of people
      attended, as well as the time of application.

PMID- 22658994
TI  - Unsaturated fatty acids as modulators of macrophage respiratory burst in the
      immune response against Rhodococcus equi and Pseudomonas aeruginosa.
AB  - In this paper, using the monocyte/macrophage cell line RAW264.7, we
      systematically investigate the impact of macrophage enrichment with unsaturated
      fatty acids on cellular radical synthesis. We found that the intracellular
      production of reactive nitrogen and oxygen intermediates depends on the
      activation status of the macrophages. For unstimulated macrophages PUFA
      enrichment resulted in an increase in cellular radical synthesis. For stimulated
      macrophages, instead, an impeding action of unsaturated fatty acids on the
      respiratory burst could be seen. Of particular importance, the impact of
      unsaturated fatty acids on the macrophage respiratory burst was also observed in
      RAW264.7 cells cocultivated with viable bacteria of the species Rhodococcus equi
      or Pseudomonas aeruginosa. PUFA supplementation of macrophages in the presence of
      R. equi or P. aeruginosa reduced the pathogen-stimulated synthesis of reactive
      nitrogen and oxygen intermediates. Furthermore, the unsaturated fatty acids were
      found to impede the expression of the myeloperoxidase gene and to reduce the
      activity of the enzyme. Hence, our data provide indications of a possible value
      of PUFA application to people suffering from chronic infections with R. equi and
      P. aeruginosa as a concomitant treatment to attenuate an excessive respiratory
      burst.

PMID- 22658995
TI  - Experimental and theoretical investigation of the molecular and electronic
      structure of 3-ethoxy-4-isopropylaminocyclobut-3-ene-1,2-dione.
AB  - The title compound, 3-ethoxy-4-isopropylaminocyclobut-3-ene-1,2-dione (EIAC) has
      been synthesized and characterized by NMR, FT-IR, UV-vis spectroscopy and single
      crystal X-ray diffraction. The (1)H NMR spectra were recorded at 300 K and 315 K
      in CDCl(3) to determine syn/anti conformers of the compound EIAC. Density
      functional theory (DFT) calculations, optimized geometrical parameters,
      vibrational frequencies and chemical shift values of syn/anti conformer in
      CDCl(3) have been performed at B3LYP/6-311G(d) level, and compared with the
      experimental data. The values provided with the calculations support the
      experimental data of the compound EIAC. The presence of NH?O type intermolecular
      H bond can be perceived from the difference between experimental calculations and
      results of FT-IR and NMR calculations. In addition, B3LYP/6-311G(d) basis set has
      been used to calculate the molecular electrostatic potential, frontier molecular
      orbitals and electronic absorption spectra. HOMO-LUMO electronic transition of
      5.12 eV is derived from the contribution of the bands n->sigma(*) or pi->pi(*).
      FT-IR, NMR and X-ray spectral results and additionally DFT calculations exhibit
      that the compound EIAC exists in keto-enamine tautomeric form. The experimental
      (1)H NMR spectra recorded at 300 K and 315 K and theoretical (1)H NMR data
      indicate that the compound EIAC is in syn conformer.

PMID- 22658996
TI  - Vibrational spectroscopic (FT-IR and FT-Raman) studies, natural bond orbital
      analysis and molecular electrostatic potential surface of 3-hydroxy-6-methyl-2
      nitropyridine.
AB  - The optimized molecular structure and corresponding vibrational assignments of 3
      hydroxy-6-methyl-2-nitropyridine have been investigated using density functional
      theory (DFT) B3LYP method with 6-311++G(d,p), 6-311++G(2d,2p) and 6-311++G(3d,3p)
      basis sets. Investigation of the relative orientation of the hydroxyl group with
      respect to the nitro group has shown that two conformers (O-cis) and (O-trans)
      exist. The vibrational analysis of the stable conformer of the title compound is
      performed by means of infrared absorption and Raman spectroscopy in combination
      with theoretical simulations. The molecular stability and bond strength were
      investigated by applying the natural bond orbital (NBO) analysis. Information
      about the size, shape, charge density distribution and site of chemical
      reactivity of the molecule has been obtained by mapping electron density
      isosurface with electrostatic potential (ESP). The isotropic chemical shift
      computed by (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of
      the HMNP calculated using the gauge invariant atomic orbital (GIAO) method also
      shows good agreement with experimental observations.

PMID- 22658997
TI  - Synthesis, spectral identification, electrochemical behavior and theoretical
      investigation of new zinc complexes of bis((E) 3-(2-nitrophenyl)-2
      propenal)propane-1,2-diimine.
AB  - Synthesis, spectroscopic, electrochemical behavior and theoretical investigation
      of some zinc complexes of a new Schiff base ligand of bis((E) 3-(2-nitrophenyl)-2
      propenal)propane-1,2-diimine (L) with a general formula of ZnLX(2)(X=Cl(-), Br(
      ), I(-), SCN(-) and N(3)(-)) are described. The ligand and its complexes were
      identified by elemental analysis, molar conductivity, UV-Visible spectra, FT-IR
      spectra, (1)H NMR and (13)C NMR spectra. The complexes were found to be molecular
      and non-electrolyte based on conductivity measurement. The spectral data confirm
      coordination of ligand and anions(X(-)) to zinc ion center. Electrochemical
      behavior of ligand and complexes were investigated by cyclic voltammetry
      technique exhibiting different redox behavior of complexes with respect to free
      ligand so that the ligand and complexes showed quasi-reversible and irreversible
      electron transfer processes respectively. Molecular structures of the ligand and
      complexes have been optimized at the UB3LYP/LANL2MB(*) level of theory.
      Accordingly some theoretical thermodynamical and/or structural parameters such as
      HF-energy, Gibbs free energy, enthalpy, selected bond distances, bond angles and
      torsion angles of optimized structures are presented.

PMID- 22658998
TI  - Hemicyanine-based colorimetric chemosensors: different recognition mechanisms for
      CN- sensing.
AB  - Simple hemicyanine dyes were synthesized by a classical condensation reaction.
      The structures of these dyes were characterized by (1)H NMR spectroscopy,
      elemental analysis, and FAB-Mass spectrometry. The sensing behavior of the
      hemicyanines towards a selection of anions was investigated by UV-vis absorption
      spectroscopy. These structurally simple dyes displayed a rapid response and high
      selectivity for cyanide ion over other common anions in the DMSO/H(2)O solution.
      Different sensing mechanism of the dyes to cyanide ion were confirmed by (1)H NMR
      studies, together with theoretical calculations based on DFT and PPP-MO methods.
      These dyes show no colorimetric response for other anions investigated.

PMID- 22658999
TI  - A BODIPY derivative as a colorimetric, near-infrared and turn-on chemosensor for
      Cu2+.
AB  - A new colorimetric and near-infrared (NIR) fluorescent chemosensor (1) for Cu(2+)
      based on BODIPY has been synthesized and investigated in this work. 1 Displays a
      high selectivity for Cu(2+) with about 250-fold enhancement in fluorescence
      emission intensity and micromolar sensitivity (K(d)=2.8+/-0.3 MUM) in comparison
      with alkali and alkaline earth metal ions (Na(+), K(+), Mg(2+), Ca(2+)) and other
      metal ions (Ba(2+), Zn(2+), Cd(2+), Fe(2+), Pb(2+), Ni(2+), Co(2+), Ag(+)) upon
      excitation at 635 nm in CH(3)CN. Meanwhile, the distinct color changes and rapid
      switch-on fluorescence also provide 1 as colorimetric senor for Cu(2+).

PMID- 22659000
TI  - BSA binding and antimicrobial studies of branched polyethyleneimine
      copper(II)bipyridine/phenanthroline complexes.
AB  - The interaction of two water soluble branched polyethyleneimine-copper(II)
      complexes containing bipyridine/phenanthroline with bovine serum albumin (BSA)
      was studied by, UV-Visible absorption, fluorescence, lifetime measurements and
      circular dichroism spectroscopic techniques. The polymer-copper(II) complexes
      strongly quench the intrinsic fluorescence of BSA is the static quenching
      mechanism through hydrogen bonds and van der Waal's attraction. The distance r,
      between the BSA and the complexes seems to be less than 2 nm indicating that the
      energy transfer between the donor and acceptor occurs with high probability.
      Synchronous fluorescence studies indicate the binding of polymer-copper(II)
      complexes with BSA mostly changes the polarity around tryptophan residues rather
      than tyrosine residues. The circular dichroism studies indicate that the binding
      has induced considerable amount of conformational changes in the protein. The
      complexes also show some antibacterial and antifungal properties.

PMID- 22659001
TI  - A fast-FENICA method on resting state fMRI data.
AB  - For resting-state fMRI data, independent component analysis (ICA) is an excellent
      method which enables the decomposition of high-dimensional data into discrete
      spatial and temporal components. Fully exploratory network ICA (FENICA), a fully
      automated and purely data-driven ICA-based analysis for group assessment of
      resting-state networks, was proposed by Schopf et al. (2010). FENICA is a novel
      and effective group assessment method, but it is not without limitations, such as
      those related to memory and time costs in running. Here we present Fast-FENICA,
      which is based on an energy sifting algorithm for interested networks, a linear
      candidate networks formation strategy and a correlation coefficients ranking
      algorithm of network matrix. It is demonstrated that the energy sifting algorithm
      for interested networks and linear candidate networks formation strategy can
      transform the stubborn computing time and memory cost limitations of FENICA from
      a quadratic level to a linear level and thus speed up the group evaluation.
      Furthermore, the correlation coefficients ranking algorithm can further increase
      the calculation speed and float up the consistent networks effectively. In
      comparison to FENICA, the hybrid data and true data experimental results
      demonstrate that Fast-FENICA not only contributes to the practicability and
      efficiency without decreasing the detecting ability of functional networks, but
      also ranks the common functional networks based on the whole spatial consistency
      at a group level. This proposed effective group analysis method is expected to
      have wide applicability.

PMID- 22659002
TI  - Brain nitric oxide: regional characterisation of a real-time microelectrochemical
      sensor.
AB  - A reliable method of directly measuring endogenously generated nitric oxide (NO)
      in real-time and in various brain regions is presented. An extensive
      characterisation of a previously described amperometric sensor has been carried
      out in the prefrontal cortex and nucleus accumbens of freely moving rats.
      Systemic administration of saline caused a transient increase in signal from
      baseline levels in both the prefrontal cortex (13 +/- 3pA, n=17) and nucleus
      accumbens (12 +/- 3pA, n=8). NO levels in the prefrontal cortex were
      significantly increased by 43 +/- 9pA (n=9) following administration of l
      arginine. A similar trend was observed in the nucleus accumbens, where an
      increase of 44 +/- 9pA (n=8) was observed when compared against baseline levels.
      Systemic injections of the non-selective NOS inhibitor l-NAME produced a
      significant decrease in current recorded in the prefrontal cortex (24 +/- 6pA,
      n=5) and nucleus accumbens (17 +/- 3pA, n=6). Finally it was necessary to
      validate the sensors functionality in vivo by investigating the effect of the
      interferent ascorbate on the oxidation current. The current showed no variation
      in both regions over the selected time interval of 60 min, indicating no
      deterioration of the polymer membrane. A detailed comparison identified
      significantly greater affects of administrations on NO sensors implanted in the
      striatum than those inserted in the prefrontal cortex and the nucleus accumbens.

PMID- 22659003
TI  - An electrophysiological monetary incentive delay (e-MID) task: a way to decompose
      the different components of neural response to positive and negative monetary
      reinforcement.
AB  - BACKGROUND: The ability to anticipate and then secure future rewards and avoid
      future punishments by responding effectively to environmental demands is at the
      core of successful decision making. Disruptions to these processes have been
      shown to be implicated in a number of psychiatric conditions. In the current
      paper we use the electrophysiological monetary incentive delay task (e-MID) to
      decompose the neural response to (i) reinforcement anticipation, (ii)
      reinforcement-contingent target processing and (iii) reinforcement-related
      feedback. METHODS: Thirty-eight adolescents and young adults performed an ERP
      based analogue of the monetary incentive delay task. ERP components previously
      associated with motivationally salient cue (cue-P3 and contingent negative
      variation, CNV), target (P3) and feedback (success vs. failure; feedback-related
      negativity; FRN and the late positive potential; LPP) stimuli were examined.
      RESULTS: Response times were shorter and less variable in the monetary gain and
      loss conditions. Distinctive ERP components were observed for each phase of
      reinforcement processing. First, cue-P3 was enhanced to monetary gain cues.
      Predicted alterations in cue-P3 following monetary loss cues and the CNV
      following cues of either monetary loss or gain were not observed. Target P3 was
      enhanced in both incentive conditions. The FRN was greater following monetary
      loss feedback. LPP amplitude was enhanced following feedback denoting monetary
      gain and the avoidance of monetary loss. CONCLUSION: Although behaviourally the
      effects of monetary loss and gain were similar, the e-MID task differentiated
      neural processing in terms of anticipation and feedback-related brain potentials.
      The e-MID task and the results of the current study provide a valuable complement
      to fMRI-based approaches to studying normal and abnormal brain correlates of
      reinforcement processing.

PMID- 22659004
TI  - Probing neural activations from continuous EEG in a real-world task: time
      frequency independent component analysis.
AB  - It is of fundamental significance to study human brain functions using
      neuroimaging technologies, such as electroencephalograph (EEG) and functional
      magnetic resonance imaging (fMRI), in real-world tasks. The present study
      explores the feasibility of using EEG to identify networked brain activations
      when subjects perform a realistic task. To robustly identify physiologically
      plausible EEG patterns related to brain activations involved in the task, a novel
      data-driven method, i.e., time-frequency independent component analysis (tfICA),
      is developed to analyze high-density EEG data, which combines the time-frequency
      analysis and complex-valued ICA method. Six classes of independent components
      (ICs) of various spatio-temporal-spectral patterns were identified across
      subjects, relating to frontal, motor, premotor, supplementary motor, secondary
      somatosensory, and occipital cortices, which suggest a networked brain activation
      involving visual perception and processing, movement planning and execution,
      working memory, performance monitoring, and decision making to accomplish the
      task. Our results indicate that temporal patterns of these ICs are consistent,
      show causal relationship among them, and of significant correlation to behavioral
      performance data recorded in same task sessions. Furthermore, the time-on-task
      effect that indicates the phenomenon of mental fatigue in sustained tasks for a
      long duration (i.e., 1h) was observed. The present study demonstrates the
      capability of the tfICA method in distinguishing various brain processes from
      continuous EEG data obtained in a realistic task and it is thus promising to
      address real-world problems, such as time-on-task fatigue.

PMID- 22659005
TI  - The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA
      during mismatch repair.
AB  - DNA mismatch repair (MMR) models have proposed that MSH (MutS homolog) proteins
      identify DNA polymerase errors while interacting with the DNA replication fork.
      MLH (MutL homolog) proteins (primarily Mlh1-Pms1 in baker's yeast) then survey
      the genome for lesion-bound MSH proteins. The resulting MSH-MLH complex formed at
      a DNA lesion initiates downstream steps in repair. MLH proteins act as dimers and
      contain long (20-30 nm) unstructured arms that connect two terminal globular
      domains. These arms can vary between 100 and 300 amino acids in length, are
      highly divergent between organisms, and are resistant to amino acid
      substitutions. To test the roles of the linker arms in MMR, we engineered a
      protease cleavage site into the Mlh1 linker arm domain of baker's yeast Mlh1
      Pms1. Cleavage of the Mlh1 linker arm in vitro resulted in a defect in Mlh1-Pms1
      DNA binding activity, and in vivo proteolytic cleavage resulted in a complete
      defect in MMR. We then generated a series of truncation mutants bearing Mlh1 and
      Pms1 linker arms of varying lengths. This work revealed that MMR is greatly
      compromised when portions of the Mlh1 linker are removed, whereas repair is less
      sensitive to truncation of the Pms1 linker arm. Purified complexes containing
      truncations in Mlh1 and Pms1 linker arms were analyzed and found to have
      differential defects in DNA binding that also correlated with the ability to form
      a ternary complex with Msh2-Msh6 and mismatch DNA. These observations are
      consistent with the unstructured linker domains of MLH proteins providing
      distinct interactions with DNA during MMR.

PMID- 22659007
TI  - Selective transfer of persistent organic pollutants and their metabolites in grey
      seals during lactation.
AB  - Twenty grey seal (Halichoerus grypus) mother-pup pairs from the colony of the
      Isle of May (Scotland) were sampled at early and late lactation in order to study
      the transfer of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers
      (PBDEs) and their metabolites (HO-PCBs and HO-PBDEs) as well as organochlorine
      pesticides (OCPs), such as DDT and metabolites (DDXs) and hexachlorobenzene
      (HCB). The transfer of the naturally produced MeO-PBDEs was also investigated.
      Generally, concentrations (on a lipid weight basis) of the sum of PCBs, PBDEs and
      DDXs tended to be higher in all tissues at late lactation (for maternal outer
      blubber SigmaPCBs=3860+/-2091 ng/g, SigmaPBDEs=120+/-74 ng/g and SigmaDDXs=559+/
      207 ng/g; for maternal inner blubber SigmaPCBs=4229+/-3274 ng/g, SigmaPBDEs=148+/
      118 ng/g and SigmaDDXs=704+/-353 ng/g; for maternal serum SigmaPCBs=1271+/-796
      ng/g, SigmaPBDEs=27+/-16 ng/g and SigmaDDXs=242+/-125 ng/g; for milk
      SigmaPCBs=1190+/-747 ng/g, SigmaPBDEs=55+/-36 ng/g and SigmaDDXs=357+/-160 ng/g;
      for pup serum SigmaPCBs=1451+/-901 ng/g, SigmaPBDEs=48+/-31 ng/g and
      SigmaDDXs=395+/-201 ng/g). In all tissues, SigmaMeO-PBDEs were found at very low
      levels or even undetected and their concentrations appeared to increase at late
      lactation only in maternal inner blubber (2.7+/-1.3 to 5.3+/-2.9 ng/g for early
      and late lactation, respectively) and milk (0.6+/-0.3 to 1.1+/-0.5 ng/g for early
      and late lactation, respectively). The transfer from inner blubber to maternal
      serum was selective and strongly depended on the log K(ow) value of the
      compounds, with less lipophilic compounds being more efficiently released. Only a
      limited amount of HO-PCBs was transferred during lactation as 4-HO-CB-107 was the
      only metabolite detected in milk (29 to 40 pg/g lw). On the contrary, most of HO
      PCB metabolites found in maternal serum were also detected in pup serum. These
      findings suggest not only a transplacental transfer of HO-PCBs from mothers to
      pups but also the possibility of endogenous biotransformation in suckling pups or
      accumulation of undetectable low amounts from milk.

PMID- 22659008
TI  - Effects of aluminum trichloride on the trace elements and cytokines in the spleen
      of rats.
AB  - The bioaccumulation and immunotoxicity of aluminum (Al) have been previously
      documented. Al accumulates in the organs of the organism, including spleen.
      Spleen is a peripheral organ of the immune system. The accumulated Al may alter
      the immune function. Here, we investigated the bioaccumulation of Al in spleen
      and its alterations in the immune system. Forty male Wistar rats (5 weeks old)
      weighed 110-120 g were orally exposed to aluminum trichloride (AlCl(3)) (0,
      64.18, 128.36 and 256.72 mg/kg body weight) in drinking water for 120 days. The
      concentrations of spleen's Al, iron (Fe), copper (Cu), zinc (Zn), interleukin-2
      (IL-2), tumor necrosis factor-alpha (TNF-alpha) and growth index were examined at
      the end of the experiment. The results showed that the concentrations of Al and
      Cu in the spleen were increased in an AlCl(3)-dose dependent manner, and the
      concentrations of spleen's growth index, Fe, Zn, IL-2 and TNF-alpha were reduced
      in AlCl(3)-treated rats. The results suggest that AlCl(3) can suppress the growth
      of spleen, disorder the balance of trace elements and inhibit the immune
      regulation of cytokines in the spleen. It indicates that AlCl(3) suppresses the
      immune function of spleen.

PMID- 22659006
TI  - Filaments from Ignicoccus hospitalis show diversity of packing in proteins
      containing N-terminal type IV pilin helices.
AB  - Bacterial motility is driven by the rotation of flagellar filaments that
      supercoil. The supercoiling involves the switching of coiled-coil protofilaments
      between two different states. In archaea, the flagellar filaments responsible for
      motility are formed by proteins with distinct homology in their N-terminal
      portion to bacterial Type IV pilins. The bacterial pilins have a single N
      terminal hydrophobic alpha-helix, not the coiled coil found in flagellin. We have
      used electron cryo-microscopy to study the adhesion filaments from the archaeon
      Ignicoccus hospitalis. While I. hospitalis is non-motile, these filaments make
      transitions between rigid stretches and curved regions and appear morphologically
      similar to true archaeal flagellar filaments. A resolution of ~7.5A allows us to
      unambiguously build a model for the packing of these N-terminal alpha-helices,
      and this packing is different from several bacterial Type IV pili whose structure
      has been analyzed by electron microscopy and modeling. Our results show that the
      mechanism responsible for the supercoiling of bacterial flagellar filaments
      cannot apply to archaeal filaments.

PMID- 22659009
TI  - Phthalates in Belgian cow's milk and the role of feed and other contamination
      pathways at farm level.
AB  - This study investigated the occurrence of dimethyl phthalate (DMP), diethyl
      phthalate (DEP), diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP),
      benzylbutyl phthalate (BBP), di(2-ethylhexyl) phthalate (DEHP), dicyclohexyl
      phthalate (DCHP) and di-n-octyl phthalate (DnOP) in raw cow's milk and feed from
      Belgian farms in order to determine their most relevant contamination pathways in
      milk. Measurable levels of DMP, DEP, DnBP, DCHP and DnOP were found in various
      feed samples, although they were not observed in milk. A plausible explanation
      for this is that they are rapidly metabolised in cows. DEHP and in a smaller
      degree also DiBP and BBP levels in milk seemed to vary across seasons and farms.
      DiBP and BBP levels were lower in summer than in winter milk, which was in
      contrast with what was observed for DEHP. This is possibly due to another feed
      composition during summer and winter. Comparing BBP and DEHP concentrations in
      manually with those in mechanically obtained milk revealed that, besides
      environmental contamination via feed ingestion, contact materials used during the
      mechanical milking process is another important contamination pathway.
      Concentrations observed in this study confirm the decreasing trend of DEHP in
      European cow's milk owing to the substitution of DEHP by other plasticisers.

PMID- 22659010
TI  - Analysis of naphthalene adduct binding sites in model proteins by tandem mass
      spectrometry.
AB  - The electrophilic metabolites of the polyaromatic hydrocarbon naphthalene have
      been shown to bind covalently to proteins and covalent adduct formation
      correlates with the cytotoxic effects of the chemical in the respiratory system.
      Although 1,2-naphthalene epoxide, naphthalene diol epoxide, 1,2-naphthoquinone,
      and 1,4-napthoquinone have been identified as reactive metabolites of interest,
      the role of each metabolite in total covalent protein adduction and subsequent
      cytotoxicity remains to be established. To better understand the target residues
      associated with the reaction of these metabolites with proteins, mass
      spectrometry was used to identify adducted residues following (1) incubation of
      metabolites with actin and protein disulfide isomerase (PDI), and (2) activation
      of naphthalene in microsomal incubations containing supplemental actin or PDI.
      All four reactive metabolites bound to Cys, Lys or His residues in actin and PDI.
      Cys17 of actin was the only residue adducted by all metabolites; there was
      substantial metabolite selectivity for the majority of adducted residues.
      Modifications of actin and PDI, following microsomal incubations containing 14C
      naphthalene, were detected readily by 2D gel electrophoresis and phosphor
      imaging. However, target modifications on tryptic peptides from these isolated
      proteins could not be readily detected by MALDI/TOF/TOF and only three modified
      peptides were detected using high resolution-selective ion monitoring (HR-SIM).
      All the reactive metabolites investigated have the potential to modify several
      residues in a single protein, but even in tissues with very high rates of
      naphthalene activation, the extent of modification was too low to allow
      unambiguous identification of a significant number of modified residues in the
      isolated proteins.

PMID- 22659011
TI  - Mixed human intra- and inter-subtype infections with the parasite Blastocystis
      sp.
AB  - Because of their limitations, current subtyping methods likely underestimate
      mixed human intra- and inter-subtype infections with Blastocystis sp. leading to
      erroneous data in the context of epidemiological studies. We confirmed this
      hypothesis by the identification of several isolates belonging to three subtypes
      in a patient considered at high risk of mixed infection through her lifestyle in
      rural area and long history of travelling.

PMID- 22659012
TI  - Structural insights into multi-protein communication systems.

PMID- 22659013
TI  - Nitric oxide--a versatile key player in cochlear function and hearing disorders.
AB  - Nitric oxide (NO) is a signaling molecule which can generally be formed by three
      nitric oxide synthases (NOS). Two of them, the endothelial nitric oxide synthase
      (eNOS) and the neural nitric oxide synthase (nNOS), are calcium/calmodulin
      dependent and constitutively expressed in many cell types. Both isoforms are
      found in the vertebrate cochlea. The inducible nitric oxide synthase (iNOS) is
      independent of calcium and normally not detectable in the un-stimulated cochlea.
      In the inner ear, as in other tissues, NO was identified as a multitask molecule
      involved in various processes such as neurotransmission and neuromodulation. In
      addition, increasing evidence demonstrates that the NO-dependent processes of
      cell protection or, alternatively, cell destruction seem to depend, among other
      things, on changes in the local cochlear NO-concentration. These alterations can
      occur at the cellular level or within a distinct cell population both leading to
      an NO-imbalance within the hearing organ. This dysfunction can result in hearing
      loss or even in deafness. In cases of cochlear malfunction, regulatory systems
      such as the gap junction system, the blood vessels or the synaptic region might
      be affected temporarily or permanently by an altered NO-level. This review
      discusses potential cellular mechanisms how NO might contribute to different
      forms of hearing disorders. Approaches of NO-reduction are evaluated and the
      transfer of results obtained from experimental animal models to human medication
      is discussed.

PMID- 22659014
TI  - Cough-related neurons in the nucleus tractus solitarius of decerebrate cats.
AB  - This study was carried out on decerebrate, paralyzed and artificially ventilated
      cats to investigate the central regulatory mechanism for cough reflex. Fictive
      cough was induced by repetitive stimulation of the superior laryngeal nerve (SLN)
      or the nucleus tractus solitarius (NTS), and characterized by an increased
      inspiratory discharge in the phrenic nerve (stage 1 of cough; S1C) and large
      burst discharge in the iliohypogastric nerve (stage 2 of cough; S2C). Membrane
      potential was recorded from the neurons located in the cough-inducible sites of
      the NTS. Seven augmenting inspiratory (aug-I), 25 inspiratory-modulated (I-mod)
      and 16 non-respiratory (non-R) neurons were encountered, all of which showed
      short-latency (7.5 +/- 1.6 ms, n=48) waves of excitatory and inhibitory
      postsynaptic potentials (EPSPs and IPSPs) in response to single pulse stimulation
      of the SLN. Out of these, all 7 aug-I and 12 I-mod neurons depolarized during the
      S1C and hyperpolarized during the S2C (DH-type response). Three I-mod and five
      non-R neurons showed membrane hyperpolarization during both stages (HH-type
      response). Ten I-mod and three non-R neurons displayed membrane depolarization
      during the S1C and S2C (DD-type response). The remaining eight non-R neurons
      showed no response during the fictive cough (NN-type response) but a long-lasting
      EPSP wave to single SLN stimulation. The NTS neurons recorded here were divided
      into three groups. Group I neurons with the NN-type response may be the second
      order relay neurons. Group II neurons with the DD-type response may integrate the
      tussigenic afferent information and send a gate signal to the cough pattern
      generator. Group III neurons with either DH-type or HH-type response may
      constitute the network of cough pattern generation or modulatory circuits
      recruited during the cough reflex. The present study suggests that Group II
      neurons may play a gating role in generating the cough reflex.

PMID- 22659015
TI  - Elevated glucose concentration changes the content and cellular localization of
      AMPA receptors in the retina but not in the hippocampus.
AB  - Diabetic retinopathy and diabetic encephalopathy are two common complications of
      diabetes mellitus. The impairment of glutamatergic neurotransmission in the
      retina and hippocampus has been suggested to be involved in the pathogenesis of
      these diabetic complications. In this study, we investigated the effect of
      elevated glucose concentration and diabetes on the protein content and surface
      expression of AMPA receptor subunits in the rat retina and hippocampus. We have
      used two models, cultured retinal and hippocampal cells exposed to elevated
      glucose concentration and an animal model of streptozotocin-induced type 1
      diabetes. The immunoreactivity of GluA1, GluA2 and GluA4 was evaluated by Western
      blot and immunocytochemistry. The levels of these subunits at the plasma membrane
      were evaluated by biotinylation and purification of plasma membrane-associated
      proteins. Elevated glucose concentration increased the total levels of GluA2
      subunit of AMPA receptors in retinal neural cells, but not of the subunits GluA1
      or GluA4. However, at the plasma membrane, elevated glucose concentration induced
      an increase of all AMPA receptor subunits. In cultured hippocampal neurons,
      elevated glucose concentration did not induce significant alterations in the
      levels of AMPA receptor subunits. In the retinas of diabetic rats there were no
      persistent changes in the levels of AMPA receptor subunits comparing to aged
      matched control retinas. Also, no consistent changes were detected in the levels
      of GluA1, GluA2 or GluA4 in the hippocampus of diabetic rats. We demonstrate that
      elevated glucose concentration induces early changes in AMPA receptor subunits,
      mainly in GluA2 subunit, in retinal neural cells. Conversely, hippocampal neurons
      seem to remain unaffected by elevated glucose concentration, concerning the
      expression of AMPA receptors, suggesting that AMPA receptors are more susceptible
      to the stress caused by elevated glucose concentration in retinal cells than in
      hippocampal neurons.

PMID- 22659018
TI  - Chloroplast gene arrangement variation within a closely related group of green
      algae (Trebouxiophyceae, Chlorophyta).
AB  - The 22 published chloroplast genomes of green algae, representing sparse
      taxonomic sampling of diverse lineages that span over one billion years of
      evolution, each possess a unique gene arrangement. In contrast, many of the >190
      published embryophyte (land plant) chloroplast genomes have relatively conserved
      architectures. To determine the phylogenetic depth at which chloroplast gene
      rearrangements occur in green algae, a 1.5-4 kb segment of the chloroplast genome
      was compared across nine species in three closely related genera of
      Trebouxiophyceae (Chlorophyta). In total, four distinct gene arrangements were
      obtained for the three genera Elliptochloris, Hemichloris, and Coccomyxa. In
      Elliptochloris, three distinct chloroplast gene arrangements were detected, one
      of which is shared with members of its sister genus Hemichloris. Both species of
      Coccomyxa examined share the fourth arrangement of this genome region, one
      characterized by very long spacers. Next, the order of genes found in this
      segment of the chloroplast genome was compared across green algae and land
      plants. As taxonomic ranks are not equivalent among different groups of
      organisms, the maximum molecular divergence among taxa sharing a common gene
      arrangement in this genome segment was compared. Well-supported clades possessing
      a single gene order had similar phylogenetic depth in green algae and
      embryophytes. When the dominant gene order of this chloroplast segment in
      embryophytes was assumed to be ancestral for land plants, the maximum molecular
      divergence was found to be over two times greater in embryophytes than in
      trebouxiophyte green algae. This study greatly expands information about
      chloroplast genome variation in green algae, is the first to demonstrate such
      variation among congeneric green algae, and further illustrates the fluidity of
      green algal chloroplast genome architecture in comparison to that of many
      embryophytes.

PMID- 22659016
TI  - Deconstructing the perineuronal net: cellular contributions and molecular
      composition of the neuronal extracellular matrix.
AB  - Perineuronal nets (PNNs) are lattice-like substructures of the neural
      extracellular matrix that enwrap particular populations of neurons throughout the
      central nervous system. Previous work suggests that this structure plays a major
      role in modulating developmental neural plasticity and brain maturation.
      Understanding the precise role of these structures has been hampered by
      incomplete comprehension of their molecular composition and cellular
      contributions to their formation, which is studied herein using primary cortical
      cell cultures. By defining culture conditions to reduce (cytosine-beta-d
      arabinofuranoside/AraC addition) or virtually eliminate (elevated potassium
      chloride (KCl) and AraC application) glia, PNN components impacted by this cell
      type were identified. Effects of depolarizing KCl concentrations alone were also
      assessed. Our work identified aggrecan as the primary neuronal component of the
      PNN and its expression was dramatically up-regulated by both depolarization and
      glial cell inhibition and additionally, the development of aggrecan-positive PNNs
      was accelerated. Surprisingly, most of the other PNN components tested were made
      in a glial-dependent manner in our culture system. Interestingly, in the absence
      of these glial-derived components, an aggrecan- and hyaluronan-reactive PNN
      developed, demonstrating that these two components are sufficient for base PNN
      assembly. Other components were expressed in a glial-dependent manner. Overall,
      this work provides deeper insight into the complex interplay between neurons and
      glia in the formation of the PNN and improves our understanding of the molecular
      composition of these structures.

PMID- 22659017
TI  - Mitochondrial distribution of neuroglobin and its response to oxygen-glucose
      deprivation in primary-cultured mouse cortical neurons.
AB  - Neuroglobin (Ngb) is a new member of the globin family and a novel endogenous
      neuroprotective molecule, but its neuroprotective mechanisms remain largely
      undefined. Previous studies suggest Ngb is both physically and functionally
      related to mitochondria, however without direct evidence. Our recent discovery
      has shown that Ngb can physically interact with a number of mitochondrial
      proteins. In this study we aimed to define the physical interaction between Ngb
      and mitochondria by determining whether there is a mitochondrial distribution of
      Ngb under both physiological-resting and pathological oxygen-glucose deprivation
      (OGD) conditions. Western blot for the first time revealed a small portion of Ngb
      was physically localized in mitochondria, and the relative mitochondrial Ngb
      level was significantly increased after OGD in primary-cultured mouse cortical
      neurons, indicating a translocation of Ngb into mitochondria. Complementary
      approaches including confocal imaging and immuno-electron microscopy confirmed
      Ngb distribution in mitochondria under both basal-resting condition and OGD.
      Inhibitors of mitochondria permeability transition pore (mPTP) and Voltage
      Dependent Anion Channel (VDAC) blocked OGD-induced increase of mitochondrial Ngb
      level, demonstrating a possible role of mPTP in Ngb's mitochondrial
      translocation. We further found that Ngb overexpression-conferred neuroprotection
      was correlated with increased mitochondrial Ngb level, suggesting the
      mitochondria distribution of Ngb is clearly associated with and may contribute to
      Ngb's neuroprotection.

PMID- 22659019
TI  - Polarity-dependent effect of low-frequency stimulation on amygdaloid kindling in
      rats.
AB  - BACKGROUND: Low-frequency stimulation (LFS, <5 Hz) has been proposed as an
      alternative option for the treatment of epilepsy. The stimulation pole, anode and
      cathode, may make different contributions to the anti-epileptic effect of LFS.
      OBJECTIVE: To determine whether electrode polarity influences the anti-epileptic
      effect of LFS at the kindling focus in amygdaloid kindling rats. METHODS: The
      effect of bipolar and monopolar (or unipolar) LFS at the amygdala in different
      polarity directions on amygdaloid kindling acquisition, kindled seizures and
      electroencephalogram (EEG) were tested. RESULTS: Bipolar LFS in the same
      direction of polarity as the kindling stimulation but not in the reverse
      direction retarded kindling acquisition. Anodal rather than cathodal monopolar
      LFS attenuated kindling acquisition and kindled seizures. Bipolar LFS showed a
      stronger anti-epileptic effect than monopolar LFS. Furthermore, anodal LFS (both
      bipolar and monopolar) decreased, while cathodal LFS increased the power of the
      EEG from the amygdala; the main changes in power were in the delta (0.5-4 Hz)
      band, which was specifically increased during kindling acquisition. CONCLUSIONS:
      Our results provide the first evidence that the effect of LFS at the kindling
      focus on amygdaloid kindling in rats is polarity-dependent, and this may be due
      to the different effects of anodal and cathodal LFS on the activity in the
      amygdala, especially on the delta band activity. So, It is likely that the
      electrode polarity, especially that for anodal current, is a key factor affecting
      the clinical effects of LFS on epilepsy.

PMID- 22659020
TI  - Functional plasticity of the motor cortical structures demonstrated by navigated
      TMS in two patients with epilepsy.
AB  - BACKGROUND: Recently, navigated transcranial magnetic stimulation (nTMS) has been
      suggested to be useful in preoperative functional localization of motor cortex in
      patients having tumors close to the somatomotor cortex. Resection of tumors in
      anatomically predicted eloquent areas without adverse effects have emphasized
      functional plasticity elicited by intracranial pathology. OBJECTIVE: To describe
      functional plasticity of motor cortex indicated by nTMS in two patients with
      epilepsy. METHODS: nTMS, functional MRI (fMRI), diffusion-tensor (DT)
      tractography and magnetoencephalography (MEG) were utilized to preoperatively
      localize motor cortical areas in the workup for epilepsy surgery. The
      localizations were compared with each other, with the cortical anatomical
      landmarks, and in one patient with invasive electrical cortical stimulation
      (ECS). RESULTS: In two out of 19 studied patients, nTMS identified motor cortical
      sites that differed from those indicated by anatomical landmarks. In one patient,
      nTMS activated preferentially premotor cortex rather than pathways originating
      from the precentral gyrus. MEG and fMRI localizations conformed with nTMS whereas
      ECS localized finger motor function into the precentral gyrus. Resection of the
      area producing motor responses in biphasic nTMS did not produce a motor deficit.
      In the other patient, nTMS indicated abnormal ipsilateral hand motor cortex
      localization and confirmed the functionality of aberrant motor cortical
      representations of the left foot also indicated by fMRI and DT-tractography.
      CONCLUSION: nTMS may reveal the functional plasticity and shifts of motor
      cortical function. Epileptic foci may modify cortical inhibition and the nTMS
      results. Therefore, in some patients with epilepsy, the nTMS results need to be
      interpreted with caution with regard to surgical planning.

PMID- 22659022
TI  - Anodal transcranial direct current stimulation (tDCS) over supplementary motor
      area (SMA) but not pre-SMA promotes short-term visuomotor learning.
AB  - BACKGROUND: Non-invasive brain stimulation such as transcranial direct current
      stimulation (tDCS) has been shown to modulate cortical excitability and thereby
      influencing motor behaviour and learning. HYPOTHESIS: While there is increasing
      knowledge about the importance of the primary motor cortex (M1) in short- and
      long-term motor skill learning, little is known about the role of secondary motor
      areas such as the supplementary and pre-supplementary motor area (SMA/pre-SMA)
      especially in short-term motor performance. Since SMA but not pre-SMA is directly
      connected to M1, we hypothesize that anodal tDCS over SMA but not pre-SMA will
      facilitate visuomotor learning. METHODS: We applied anodal tDCS (tDCS(anodal))
      over left SMA, pre-SMA or M1 (n=12 in each group) while subjects performed a
      visuomotor pinch force task (VPFT) with their right hand and compared VPFT
      performance relative to sham (tDCS(sham)). RESULTS: For the first time, we could
      show that apart from tDCS(anodal) over left M1 also SMA but not pre-SMA
      stimulation promotes short-term improvements in visuomotor learning relative to
      tDCS(sham). CONCLUSIONS: Our findings provide novel evidence about the role of
      SMA in short-term visuomotor performance. This knowledge might be beneficial in
      developing hypothesis-driven clinical studies in neurorehabilitation.

PMID- 22659021
TI  - Intermittent theta burst stimulation over ipsilesional primary motor cortex of
      subacute ischemic stroke patients: a pilot study.
AB  - BACKGROUND: We demonstrated that prolonged transcranial magnetic intermittent
      theta burst stimulation (iTBS, 1200 pulses/session=iTBS1200) produces longer
      lasting facilitation in corticospinal excitability than ordinary form of iTBS in
      healthy subjects. OBJECTIVE: Here we show the safety and small-scale efficacy of
      iTBS1200 over ipsilesional primary motor cortex (M1) in subacute stroke patients.
      METHODS: Twelve patients with first-time, subacute ischemic stroke of the middle
      cerebral artery were randomized into two groups that received 10 daily-sessions
      of either iTBS1200 or sham stimulation (n=6/group) over ipsilesional M1 hand
      region in addition to medical and rehabilitation treatments. The primary outcome
      measures were safety and tolerability. The secondary outcome measures included
      the National Institute of Health Stroke Scale (NIHSS), Upper Extremity Fugl-Meyer
      Test (UE-FMT), Action Research Arm Test (ARAT), active motor thresholds
      (aMTs)/motor-evoked potentials (MEPs) from the extensor carpi radialis (ECR), and
      magnetoencephalography on post-intervention day 1 and post-stroke day 60.
      RESULTS: iTBS or sham stimulation was well tolerated by all patients without
      seizures or significant adverse effects. Compared with the matched controls, the
      iTBS group showed measurable improvements in the NIHSS and the proximal UE-FMT
      scores on post-intervention day 1 and post-stroke day 60. Nevertheless, the hand
      ARAT scores, aMT and MEPs from the paretic ECR were not different between groups.
      Post-movement beta synchronization increased over iTBS-conditioned M1 on post
      intervention day 1 in testable patients. CONCLUSIONS: Repetitive sessions of
      iTBS1200 over ipsilesional M1 of subacute stroke patients are safe and the
      potential benefits encourage a larger trial to determine the efficacy in stroke
      patients. (ClinicalTrials.gov: NCT-01323881).

PMID- 22659023
TI  - The diagnostic performance of classical molecular tests used for detecting human
      papillomavirus.
AB  - Cervical samples were evaluated for human papillomavirus (HPV) presence using the
      hybrid capture-2 (HC2) assay and the polymerase chain reaction (PCR) with three
      different primer sets (GP5+/6+, MY09/11 and pU1M/2R). PCR results were compared
      to HC2 and results of all assays were compared to cytological and colposcopy
      findings. Post-test probability was assessed in individual assays and test
      combinations. HPV-DNA prevalence was 36.5% with HC2 and 55.2% with PCR. MY09/11
      detected HPV-DNA in 38% of samples, GP5+/6+ in 19.1% and pU1M/2R in 16.4%.
      pU1M/2R and HC2 had the highest concordance (75.31%, k=0.39 in the whole
      population; 74.1%, k=0.5 in women with abnormal cytology). pU1M/2R had the best
      diagnostic performance, including optimal post-test probabilities and cervical
      abnormality detection (individually or in a panel of tests). Women positive for
      pU1M/2R may be at higher risk of disease progression; the assay performance when
      combined with a Pap smear in cervical cancer screening programs should be
      evaluated.

PMID- 22659024
TI  - Directed rotations of single porphyrin molecules controlled by localized force
      spectroscopy.
AB  - Directed molecular repositioning is a key step toward the build up of molecular
      machines. To artificially generate and control the motion of molecules on a
      surface, excitations by light, chemical, or electrical energy have been
      demonstrated. Here, the application of local mechanical forces is implemented to
      achieve directed rotations of molecules. Three-dimensional force spectroscopy
      with sub-Angstrom precision is used to characterize porphyrin derivatives with
      peripheral carbonitrile groups. Extremely small areas on these molecules (~ 100 *
      100 pm(2)) are revealed which can be used to control rotations. In response to
      the local mechanical forces, the molecular structure elastically deforms and then
      changes its conformation, which leads to its rotation. Depending on the selection
      of one of four submolecular areas, the molecule is either rotated clockwise or
      counterclockwise.

PMID- 22659025
TI  - Gains of item-specific training in visual working memory and their neural
      correlates.
AB  - Experts sometimes show higher working memory performance than novices but
      contrary to this finding, evidence for a positive effect of item-specific
      training is rare. This study provides evidence for item-specific training gains.
      We presented Chinese characters and artificial patterns (spotted figures) in a
      change detection task before and after training (varying set size from 1 to 3). A
      part of the Chinese characters were trained; others and the spotted figures were
      not trained. Memory capacity was between one and two items. For set size two,
      memory performance for trained characters was higher than for untrained
      characters and they were processed faster. Within superior intraparietal sulcus
      and middle occipital cortex (part of the putative posterior working memory
      network), the neural activity asymptotically increased with set size. Untrained
      items reached the activation maximum already at set size two. For this set size,
      the activity was significantly reduced for trained items so that a further
      increase from two to three items was observed. We interpret this difference as a
      correlate of a gain in neural efficiency. The size of this difference correlated
      with the training gain in memory. We assume that training causes a more efficient
      neural representation of trained items supported by long-term memory and this
      allows holding more items in working memory.

PMID- 22659026
TI  - Cortical spreading depression differentially affects lysine methylation of H3
      histone at neuroprotective genes and retrotransposon sequences.
AB  - Recently cortical spreading depression (CSD) has been hypothesized to involve
      epigenetic control of gene expression, by inducing an overall decrease of H3K4
      and increase of H3K9 di-methylation. Here we evaluated the H3K4 and H3K9 di
      methylation level at specific loci in rat brains 24 h after CSD induction.
      Analysis of two selected neuroprotective genes, iNOS and HIF-1alpha, showed
      marked increase in lysine 4 di-methylation and decrease in lysine 9 di
      methylation of H3 histone. In addition, di-methylation of H3K4 increased moving
      toward 5' end of the genes in CSD-induced rat hemispheres. Such behavior may
      reflect an epigenetic molecular memory of actively transcribed genes. We extended
      our analysis on the H3K4 and H3K9 di-methylation levels of two long interspersed
      sequences (LINEs). We showed that CSD induction led to di-methylation decrease in
      lysine 4 and increase in lysine 9 of H3 histone, a trend which reflected the
      overall chromatin changes previously demonstrated. In conclusion, our data
      corroborate the hypothesis that epigenetic regulation of gene expression can be
      affected by CSD and that might be a pivotal molecular mechanism of CSD-induced
      preconditioning phenomenon which induces tolerance to a subsequent episode of
      ischemia. In such control, we evidenced two effects: i) a molecular memory of
      transcribed neuroprotective genes, ii) an epigenetic silencing of
      retrotransposable sequences.

PMID- 22659027
TI  - Neuregulin1beta1 protects oligodendrocyte progenitor cells from oxygen glucose
      deprivation injury induced apoptosis via ErbB4-dependent activation of PI3
      kinase/Akt.
AB  - Mounting evidence suggests that the injury of oligodendrocyte progenitor cells
      (OPCs) caused by hypoxia plays a pivotal role in periventricular white matter
      injury (PWMI) causation. We investigated the potential role of active
      extracellular domain of Neuregulin1 isotypebeta1 (NRG1beta1)/ErbB signaling in
      protecting OPCs from oxygen glucose deprivation (OGD) induced apoptosis. At
      different time points, endogenous NRG1beta1 protein was analyzed after OGD.
      Escalating dosages of NRG1beta1 were used to treat OPCs with OGD, and the
      apoptosis was measured, as well as the expression of ErbB receptors, Akt and Erk
      phosphorylation and caspase3 activation. OGD damage resulted in decreased
      expression of endogenous NRG1beta1. In parallel, NRG1beta1 treatment promoted the
      expression of p-ErbB4 receptor, phosphorylated Akt and inhibited caspase3
      activation. Furthermore, the activation of PI3-kinase/Akt by NRG1beta1 was ErbB4
      dependent. Our data demonstrated that NRG1beta1 protected OPCs from OGD induced
      apoptosis and the possible protective mechanism is linking with ErbB4-dependent
      activation of PI3-kinase/Akt pathway.

PMID- 22659028
TI  - Genome-scale analysis of human mRNA 5' coding sequences based on expressed
      sequence tag (EST) database.
AB  - The "5' end mRNA artifact" issue refers to the incorrect assignment of the first
      AUG codon in an mRNA, due to the incomplete determination of its 5' end sequence.
      We performed a systematic identification of coding regions at the 5' end of all
      human known mRNAs, using an automated expressed sequence tag (EST)-based
      approach. Following parsing of more than 7 million BLAT alignments, we found 477
      human loci, out of 18,665 analyzed, in which an extension of the mRNA 5' coding
      region was identified. Proof-of-concept confirmation was obtained by in vitro
      cloning and sequencing for GNB2L1, QARS and TDP2 cDNAs, and the consequences for
      the functional studies of these loci are discussed. We also generated a list of
      20,775 human mRNAs where the presence of an in-frame stop codon upstream of the
      known start codon indicates completeness of the coding sequence at 5' in the
      current form.

PMID- 22659031
TI  - Classification of primary immunodeficiency disorders: one-fits-all does not help
      anymore.

PMID- 22659029
TI  - Estrogen receptor alpha modulates Toll-like receptor signaling in murine lupus.
AB  - Systemic lupus erythematosus (SLE) is a disease that disproportionately affects
      females. Despite significant research effort, the mechanisms underlying the
      female predominance in this disease are largely unknown. Previously, we showed
      that estrogen receptor alpha knockout (ERalphaKO) lupus prone female mice had
      significantly less pathologic renal disease and proteinuria, and significantly
      prolonged survival. Since autoantibody levels and number and percentage of B/T
      cells were not significantly impacted by ERalpha genotype, we hypothesized that
      the primary benefit of ERalpha deficiency in lupus nephritis was via modulation
      of the innate immune response. Using BMDCs and spleen cells/B cells from female
      wild-type or ERalphaKO mice, we found that ERalphaKO-derived cells have a
      significantly reduced inflammatory response after stimulation with TLR agonists.
      Our results indicate that the inflammatory response to TLR ligands is
      significantly impacted by the presence of ERalpha despite the absence of
      estradiol, and may partially explain the protective effect of ERalpha deficiency
      in lupus-prone animals.

PMID- 22659032
TI  - miRNA in systemic lupus erythematosus.
AB  - Since their recent discovery, the small noncoding RNA known as microRNAs (miRNA)
      have been reported to play a major role in the physiological control of gene
      expression and in the pathogenesis of malignant, infectious, and autoimmune
      disorders. In systemic lupus erythematosus (SLE), an autoimmune disease
      characterized by the presence of autoantibodies to multiple antigens, the role of
      miRNA as post-transcriptional regulators of different aspects of the disease
      process has recently emerged. This article reviews the pertinent literature and
      mechanisms of action of miRNA that have so far been associated with the
      pathogenesis of SLE.

PMID- 22659030
TI  - Associations of cytokines, sleep patterns, and neurocognitive function in youth
      with HIV infection.
AB  - Youth infected with HIV at birth often have sleep disturbances, neurocognitive
      deficits, and abnormal psychosocial function which are associated with and
      possibly resulted from elevated blood cytokine levels that may lead to a
      decreased quality of life. To identify molecular pathways that might be
      associated with these disorders, we evaluated 38 HIV-infected and 35 uninfected
      subjects over 18-months for intracellular cytokine levels, sleep patterns and
      duration of sleep, and neurodevelopmental abilities. HIV infection was
      significantly associated with alterations of intracellular pro-inflammatory
      cytokines (TNF-alpha, IFN-gamma, IL-12), sleep factors (total time asleep and
      daytime sleep patterns), and neurocognitive factors (parent and patient reported
      problems with socio-emotional, behavioral, and executive functions; working
      memory-mental fatigue; verbal memory; and sustained concentration and vigilance.
      By better defining the relationships between HIV infection, sleep disturbances,
      and poor psychosocial behavior and neurocognition, it may be possible to provide
      targeted pharmacologic and procedural interventions to improve these debilitating
      conditions.

PMID- 22659033
TI  - The origin and properties of extracellular DNA: from PAMP to DAMP.
AB  - DNA is a polymeric macromolecule whose biological activities depend on location
      as well as binding to associated molecules. Inside the cell, DNA is the source of
      genetic information and binds histones to form nucleosomes. DNA can exit the
      cell, however, to enter the extracellular space primarily during cell death,
      either apoptosis or necrosis, as well as NETosis. While bacterial DNA is a potent
      immune stimulant by virtue of its CpG motifs, mammalian DNA, which is ordinarily
      inactive, can acquire activity by associating with nuclear, cytoplasmic and serum
      proteins which promote its uptake into cells to stimulate internal DNA sensors,
      including Toll-like receptor 9. Among these proteins, anti-DNA autoantibodies can
      form immune complexes with DNA to stimulate plasmacytoid dendritic cells to
      produce type 1 interferon. Together, these findings suggest that the immune
      properties of DNA are mutable and diverse, reflecting its context and the array
      of attached molecules.

PMID- 22659034
TI  - CD44 as a novel target for treatment of staphylococcal enterotoxin B-induced
      acute inflammatory lung injury.
AB  - Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB),
      can lead to the induction of acute lung injury/acute respiratory distress
      syndrome (ALI/ARDS). In the current study, we investigated the role of CD44 in
      ALI/ARDS. Intranasal exposure of CD44 wild-type mice to SEB led to a significant
      increase in the expression of CD44 on lung mononuclear cells. CD44 knockout mice
      developed significantly reduced SEB-induced ALI/ARDS, through reduced
      inflammatory cytokine production and reduced lung inflammatory cells, compared to
      similarly treated CD44 wild-type mice. Mechanistically, deletion of CD44 altered
      SEB-induced cytokine production in the lungs and reduced the ability of SEB
      exposed leukocytes to bind to lung epithelial cells. Finally, treatment of SEB
      exposed mice with anti-CD44 mAbs led to significant reduction in vascular
      permeability, reduction in cytokine production, and prevented inflammatory cell
      infiltration in the lungs. Together, these results suggest the possibility of
      targeting CD44 for the treatment of SEB-induced ALI/ARDS.

PMID- 22659035
TI  - Why do women get lupus?

PMID- 22659036
TI  - Our food: packaging & public health.

PMID- 22659037
TI  - A theoretical study on the role of Ca(2+)-activated K+ channels in the regulation
      of hormone-induced Ca2+ oscillations and their synchronization in adjacent cells.
AB  - BACKGROUND INFORMATION: In many non-excitable cells hormone stimulation triggers
      repetitive oscillations of the intracellular Ca(2+) concentration, thought to be
      important in several cell functions. Although most of these cells respond to an
      elevation of the intracellular Ca(2+) concentration with a membrane
      hyperpolarization, due to the activation of Ca(2+)-activated K(+) channels,
      theoretical models do not usually consider the contribution of the membrane
      potential dynamics in defining the properties of the intracellular Ca(2+)
      concentration oscillations and their synchronization in adjacent, coupled cells.
      RESULTS: We developed a theoretical model of intracellular Ca(2+) oscillations
      that includes the dynamics of the membrane potential controlled by the cyclic
      activation of Ca(2+)-activated K(+) channels. We found that membrane potential
      oscillations determine an in-phase oscillating Ca(2+) influx that significantly
      affects the amplitude, duration and oscillatory frequency of the intracellular
      Ca(2+) concentration oscillations. Under specific levels of hormone stimulation
      Ca(2+)-activated K(+) channels are essential for establishing or inhibiting the
      intracellular Ca(2+) concentration oscillatory activity, as also suggested by
      some experimental findings. We also found that in electrically coupled cells
      displaying Ca(2+)-activated K(+) channels-induced membrane potential
      oscillations, the synchronization of intracellular Ca(2+) concentration
      oscillations in adjacent cells can occur in the complete absence of gap junction
      Ca(2+) or inositol trisphosphate diffusion, the simple electrical coupling being
      sufficient for synchronization. Finally, electrical coupling between adjacent
      cells was found to work in synergy with gap junction Ca(2+) permeability in the
      synchronization of intracellular Ca(2+) concentration oscillations, making it to
      occur at lower gap junction Ca(2+) permeabilities. CONCLUSIONS: Data from our
      model indicate that Ca(2+)-activated K(+) channel activity may be critical to
      establish important properties of the intracellular Ca(2+) concentration
      oscillations, and may help synchronize intracellular Ca(2+) concentration
      oscillations in electrically coupled cells. The model we propose here thus
      represents a third model of synchronization of intracellular Ca(2+) concentration
      oscillations in adjacent cells, based exclusively on the gap junction electrical
      coupling between cells displaying Ca(2+)-activated K(+) channel-induced membrane
      potential oscillations.

PMID- 22659038
TI  - Male fecundity and optimal gametocyte sex ratios for Plasmodium falciparum during
      incomplete fertilization.
AB  - A mathematical model of the within-vector dynamics of Plasmodium falciparum in an
      Anopheles mosquito with unbiased random mating and incomplete fertilization is
      used to investigate the effects of varying fecundity and population size on the
      gametocyte sex ratio when strains maximize their individual fitnesses. Previous
      studies considered either the effects of variable fecundity or the effects of
      incomplete fertilization. Here we investigate the simultaneous effects of
      variable fecundity, incomplete fertilization, and variable number of ingested
      gametocytes per strain on the optimal gametocyte sex ratio. Our model results
      agree with others in the case of two identically sized populations in that large
      differences in fecundities lead to female-biased total population sex ratios.
      When the assumption of identically sized populations is relaxed in our model,
      population sex ratios vary from highly female-biased to slightly male-biased,
      depending on relative strain fecundities and population sizes. Our results
      provide a plausible explanation for the high variation in gametocyte sex ratios
      of P. falciparum observed in nature.

PMID- 22659039
TI  - The role of tunable activation thresholds in the dynamics of autoimmunity.
AB  - It has been known for some time that human autoimmune diseases can be triggered
      by viral infections. Several possible mechanisms of interactions between a virus
      and immune system have been analysed, with a prevailing opinion being that the
      onset of autoimmunity can in many cases be attributed to "molecular mimicry",
      where linear peptide epitopes, processed from viral proteins, mimic normal host
      self-proteins, thus leading to a cross-reaction of immune response against virus
      with host cells. In this paper we present a mathematical model for the dynamics
      of an immune response to a viral infection and autoimmunity, which takes into
      account T cells with different activation thresholds. We show how the infection
      can be cleared by the immune system, as well as how it can lead to a chronic
      infection or recurrent infection with relapses and remissions. Numerical
      simulations of the model are performed to illustrate various dynamical regimes,
      as well as to analyse the potential impact of treatment of autoimmune disease in
      the chronic and recurrent states. The results provide good qualitative agreement
      with available data on immune responses to viral infections and progression of
      autoimmune diseases.

PMID- 22659040
TI  - TH17 functional study in severe asthma using agent based model.
AB  - TH17 is a subset of CD4+T cells. Comparing to common asthma patients, there are
      more TH17 cells in the respiratory systems of the patients with severe asthma.
      TH17 cells are mainly adjusted by IL23 to produce IL17A and IL17F, which act on
      the epithelial cells and cause severe asthma. However, the TH17 function in
      severe asthma as a driving mechanism of neutrophilic inflammation is not yet
      fully understood and deserves further study. However, it is very difficult to
      describe the interactions between TH17 and other cells using mathematics
      equations due to the high complexity of immunity system. In order to explore the
      TH17 function in severe asthma, we used BIS (Basic Immune Simulator) platform to
      simulate TH17 models, and compared DC (Dendritic Cell) models with TH17 models.
      We studied the interaction between innate immune and adaptive immune cells, which
      was resulted from TH17 cells. The simulation results for the TH17 models are
      consistent with clinical data, which suggests that DC-IL23-TH17 axis might be the
      path of causing severe asthma. Our simulation studies support a role for TH17 in
      severe asthma, and hence it could be taken as a new target candidate for clinical
      treatment of severe asthma.

PMID- 22659041
TI  - The biological control of disease vectors.
AB  - Vector-borne diseases are common in nature and can have a large impact on humans,
      livestock and crops. Biological control of vectors using natural enemies or
      competitors can reduce vector density and hence disease transmission. However,
      the indirect interactions inherent in host-vector disease systems make it
      difficult to use traditional pest control theory to guide biological control of
      disease vectors. This necessitates a conceptual framework that explicitly
      considers a range of indirect interactions between the host-vector disease system
      and the vector's biological control agent. Here we conduct a comparative analysis
      of the efficacy of different types of biological control agents in controlling
      vector-borne diseases. We report three key findings. First, highly efficient
      predators and parasitoids of the vector prove to be effective biological control
      agents, but highly virulent pathogens of the vector also require a high
      transmission rate to be effective. Second, biocontrol agents can successfully
      reduce long-term host disease incidence even though they may fail to reduce long
      term vector densities. Third, inundating a host-vector disease system with a
      natural enemy of the vector has little or no effect on reducing disease
      incidence, but inundating the system with a competitor of the vector has a large
      effect on reducing disease incidence. The comparative framework yields
      predictions that are useful in developing biological control strategies for
      vector-borne diseases. We discuss how these predictions can inform ongoing
      biological control efforts for host-vector disease systems.

PMID- 22659042
TI  - A comparison of two methods to estimate additive-by-additive interaction of QTL
      effects by a simulation study.
AB  - Additive-by-additive epistasis plays an important role in the genetic
      architecture of complex traits. The parameter connected with the additive-by
      additive interaction can influence decisions concerning usefulness of the
      breeding material for the generation of new genotypes with characteristics
      improved over the parental forms. This study presents comparisons of two
      estimation methods of additive-by-additive interactions of QTL effects by the
      Monte Carlo simulation study. In the first method we assume that we observed only
      the plant phenotype, while in the second method we have additional information
      from the molecular marker observations. The obtained results show that the
      additive-by-additive interaction effect calculated on the basis of the marker
      observations is always smaller than the total additive-by-additive interaction
      effect obtained from phenotypic observations only. The lack of influence of the
      distance between markers and the number of linkage groups on the estimation of
      effects of additive-by-additive epistasis interaction genes by the two methods
      shows that both these methods may be used for different genetic maps and for
      different plant species.

PMID- 22659044
TI  - On the evolution of coarse categories.
AB  - We compare the evolutionary fitness of different cultures (or populations), where
      we think of culture as partitioning a set of decision situations into categories
      of situations treated the same. Information about optimal behavior in each
      category is passed on via a process of noisy cultural transmission. We show that
      coarse partitions (distinguishing less situations) can provide higher
      evolutionary fitness even if there are no explicit costs to holding finer
      partitions.

PMID- 22659043
TI  - Piecewise HIV virus dynamic model with CD4(+) T cell count-guided therapy: I.
AB  - The strategies of structured treatment interruptions (STIs) of antiretroviral
      therapies have been proposed for clinical management of HIV infected patients,
      but clinical studies on STIs failed to achieve a consistent conclusion for this
      strategy. To evaluate the STI strategies, in particular, CD4(+) T cell count
      guided STIs, and explain these controversial conclusions from different clinical
      studies, in this paper we propose to use piecewise HIV virus dynamic models to
      quantitatively explore the STI strategies and investigate their dynamic
      behaviors. Our analysis results indicate that CD4(+) T cell counts can be
      maintained above a safe level using the STI with a single threshold or a
      threshold window. Numerical simulations show that the CD4(+) T cell counts either
      fluctuate or approach a stable level for a patient, depending on the prescribed
      upper or lower threshold values. In particular, the CD4(+) T cell counts can be
      stabilized at a desired level if the threshold policy control is applied. The
      durations of drug-on and drug-off are very sensitive to the prescribed upper or
      lower threshold levels, which possibly explains why the on-off strategy with
      fixed schedule or an STI strategy with frequent switches are associated with the
      high rate of failure. Our findings suggest that it is critical to carefully
      choose the thresholds of CD4(+) T cell count and individualize the STIs for each
      individual patient based on initial CD4(+) T cell counts.

PMID- 22659045
TI  - Involvement of the MAPK and RhoA/ROCK pathways in PGE2-mediated CCR7-dependent
      monocyte migration.
AB  - Prostaglandin E(2) (PGE(2)) induces the expression of C-C chemokine receptor type
      7 (CCR7) on human monocytes, thereby enabling their subsequent migration in
      response to CCL19 and CCL21, the natural ligands for CCR7. To date, important
      mediators of PGE(2)-mediated monocyte migration remain unknown. In this study, we
      explored the role of mitogen-activated protein kinases and the RhoA/Rho
      associated protein kinase (ROCK) pathway in CCR7-dependent monocyte migration in
      the presence of PGE(2). Our results indicate that CCL19 binding to CCR7 promotes
      the activation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N
      terminal kinase and leads to monocyte migration. Moreover, the RhoA/ROCK pathway
      was essential for PGE(2)-mediated CCR7-dependent monocyte migration.

PMID- 22659046
TI  - A new unibody branched stent-graft for reconstruction of the canine aortic arch.
AB  - OBJECTIVES: To evaluate the feasibility and safety of a new unibody branched
      stent-graft for reconstruction of the canine aortic arch. MATERIALS AND METHODS:
      Twenty adult hybrid dogs were used for the experiments. Ten dogs were implanted
      with single-branched stent-grafts; the other ten dogs were implanted with double
      branched stent-grafts. The stent-grafts were implanted transluminally via the
      abdominal aorta. The branched limbs were caught and pulled into supra-aortic
      vessels using gooseneck snare wires introduced via the axillary arteries. The
      animals were euthanized 4 months after implantation. RESULTS: One of the ten dogs
      implanted with a single-branched stent-graft died from failure of the
      implantation procedure, and two of the ten dogs implanted with double-branched
      stent-grafts died from failure of the procedure and excessive blood loss. After
      month 4, the remaining unibody branched stent-grafts were patent and did not
      migrate. CONCLUSIONS: This new unibody branched stent-graft could be used to
      reconstruct the aortic arch. This is a total endovascular technique, and compared
      to other branched stent-grafts appears to be safer and easier to implant.

PMID- 22659047
TI  - Cytotoxic effects of gold nanoparticles: a multiparametric study.
AB  - The in vitro labeling of therapeutic cells with nanoparticles (NPs) is becoming
      more and more common, but concerns about the possible effects of the NPs on the
      cultured cells are also increasing. In the present work, we evaluate the effects
      of poly(methacrylic acid)-coated 4 nm diameter Au NPs on a variety of sensitive
      and therapeutically interesting cell types (C17.2 neural progenitor cells, human
      umbilical vein endothelial cells, and PC12 rat pheochromocytoma cells) using a
      multiparametric approach. Using various NP concentrations and incubation times,
      we performed a stepwise analysis of the NP effects on cell viability, reactive
      oxygen species, cell morphology, cytoskeleton architecture, and cell
      functionality. The data show that higher NP concentrations (200 nM) reduce cell
      viability mostly through induction of reactive oxygen species, which was
      significantly induced at concentrations of 50 nM Au NPs or higher. At these
      concentrations, both actin and tubulin cytoskeleton were deformed and resulted in
      reduced cell proliferation and cellular differentiation. In terms of cell
      functionality, the NPs significantly impeded neurite outgrowth of PC12 cells up
      to 20 nM concentrations. At 10 nM, no significant effects on any cellular
      parameter could be observed. These data highlight the importance of using
      multiple assays to cover the broad spectrum of cell-NP interactions and to
      determine safe NP concentrations and put forward the described protocol as a
      possible template for future cell-NP interaction studies under comparable and
      standardized conditions.

PMID- 22659048
TI  - Involvement of glutathione peroxidase 1 in growth and peroxisome formation in
      Saccharomyces cerevisiae in oleic acid medium.
AB  - Saccharomyces cerevisiae is able to use some fatty acids, such as oleic acid, as
      a sole source of carbon. beta-oxidation, which occurs in a single membrane
      enveloped organelle or peroxisome, is responsible for the assimilation of fatty
      acids. In S. cerevisiae, beta-oxidation occurs only in peroxisomes, and H(2)O(2)
      is generated during this fatty acid-metabolizing pathway. S. cerevisiae has three
      GPX genes (GPX1, GPX2, and GPX3) encoding atypical 2-Cys peroxiredoxins. Here we
      show that expression of GPX1 was induced in medium containing oleic acid as a
      carbon source in an Msn2/Msn4-dependent manner. We found that Gpx1 was located in
      the peroxisomal matrix. The peroxisomal Gpx1 showed peroxidase activity using
      thioredoxin or glutathione as a reducing power. Peroxisome biogenesis was induced
      when cells were cultured with oleic acid. Peroxisome biogenesis was impaired in
      gpx1? cells, and subsequently, the growth of gpx1? cells was lowered in oleic
      acid-containing medium. Gpx1 contains six cysteine residues. Of the cysteine
      substituted mutants of Gpx1, Gpx1(C36S) was not able to restore growth and
      peroxisome formation in oleic acid-containing medium, therefore, redox regulation
      of Gpx1 seems to be involved in the mechanism of peroxisome formation.

PMID- 22659049
TI  - Vasorelaxant activity of some structurally related triterpenic acids from
      Phoradendron reichenbachianum (Viscaceae) mainly by NO production: ex vivo and in
      silico studies.
AB  - The aim of the current study was to investigate the vasorelaxant activity of five
      structurally-related triterpenic acids namely ursolic (1), moronic (2), morolic
      (3), betulinic (4) and 3,4-seco-olean-18-ene-3,28-dioic (5) acids. The
      vasorelaxant effect of compounds 1-5 were determined on endothelium-denuded and
      endothelium-intact rat aortic rings pre-contracted with noradrenaline (0.1 MUM).
      All compounds showed significant relaxant effect on endothelium-intact vessels in
      a concentration-dependent manner (p<0.05). Ursolic, moronic and betulinic acids
      were the most potent vasorelaxant agents with 11.7, 16.11 and 58.46 MUM,
      respectively. Since vasorelaxation was blocked by L-NAME, while indomethacin did
      not inhibit the effect, endothelium-derived nitric oxide seems to be involved in
      triterpenic 2 and 3 mode of action. Compounds 1-5 were docked with a crystal
      structure of eNOS. Triterpenes 1-5 showed calculated affinity with eNOS in the C1
      and C2 binding pockets, near the catalytic site; Ser248 and Asp480 are the
      residues that make hydrogen bonds with the triterpene compounds.

PMID- 22659050
TI  - PEGylation of interleukin-10 improves the pharmacokinetic profile and enhances
      the antifibrotic effectivity in CCl4-induced fibrogenesis in mice.
AB  - Liver fibrosis represents a scar formation process as a response to chronic
      injury and a major cause of death worldwide. To date, no drug is available for
      this condition. Interleukin-10 (IL-10) has potent anti-inflammatory and
      antifibrotic properties but its short half-life in the circulation hampers its
      clinical use. Our aim was therefore to modify IL-10 with polyethylene glycol
      (PEG) to prolong its circulation time and enhance its effectivity. IL-10 was
      modified with 5 or 20 kDa PEG. The biological activity was preserved after
      PEGylation as assessed by inhibition of TNF-alpha production by macrophages. In
      vivo, during CCl(4)-induced fibrogenesis in mice, both 5PEG-IL-10 and 20PEG-IL-10
      showed a longer circulation time compared to IL-10, which was associated with a
      significant increased liver accumulation. Immunohistochemical analysis of
      fibrotic livers of mice receiving treatment with IL-10 or its PEGylated forms,
      revealed a decrease in markers reflecting HSC and KC activation induced by 5PEG
      IL10. Transcription levels of IL-6 were decreased upon treatment with IL-10 and
      both PEGylated forms, whereas IL-1beta levels were only down-regulated by 5PEGIL
      10 and 20PEGIL-10. We conclude that PEGylation of IL-10 is a good strategy to
      attenuate liver fibrosis and that 5PEGIL-10 is the most effective conjugate.

PMID- 22659051
TI  - One study, two paths: the challenge of dual-use research.

PMID- 22659052
TI  - Identification and analysis of genes differentially expressed in the Spodoptera
      litura fat body in response to the biocontrol fungus, Nomuraea rileyi.
AB  - Nomuraea rileyi is an important pathogenic fungus that can successfully control
      Spodoptera litura. However, little is known on how S. litura responds to N.
      rileyi infection. A forward suppression subtractive hybridization (SSH) cDNA
      library was constructed from the S. litura fat body and the up-regulated genes
      were identified to isolate differentially expressed genes in response to N.
      rileyi. A total of 345/1175 random clones screened by cDNA array dot blotting
      were sequenced, resulting in 117 uniquely expressed sequence tags (ESTs).
      Potential functional genes were identified by BLAST searches and were categorized
      into seven groups associated with different biological processes based on the
      literature and gene ontologies. Among 117 genes, 74 had matches in the non
      redundant (NR) protein database and were found to be involved in different
      biological processes, while 43 of the screened genes were classified to the
      "unknown function" gene group. Notably, only two genes had previously been
      reported in S. litura and most of the screened genes showed less similarity to
      known sequences based on BLASTn results, suggesting that 115 genes were found for
      the first time in S. litura. Semi-quantitative RT-PCR analysis of seven randomly
      selected genes revealed that most were differentially expressed after N. rileyi
      infection. qRT-PCR analysis confirmed that four genes (Hsp70, Hsp90,
      gallerimycin, and cysteine proteinase) were significantly up-regulated after N.
      rileyi infection. Taken together, the present study identified up-regulated S.
      litura genes in response to N. rileyi infection. Further investigations are
      needed to unravel the molecular mechanisms of the genes or proteins potentially
      involved in the S. litura innate immune defense against N. rileyi infection.

PMID- 22659053
TI  - Identification of the thiamin pyrophosphokinase gene in rainbow trout:
      characteristic structure and expression of seven splice variants in tissues and
      cell lines and during embryo development.
AB  - Thiamin pyrophosphokinase (TPK) converts thiamin to its active form, thiamin
      diphosphate. In humans, TPK expression is down-regulated in some thiamin
      deficiency related syndrome, and enhanced during pregnancy. Rainbow trout are
      also vulnerable to thiamin deficiency in wild life and are useful models for
      thiamin metabolism research. We identified the tpk gene transcript including
      seven splice variants in the rainbow trout. Almost all cell lines and tissues
      examined showed co-expression of several tpk splice variants including a
      potentially major one at both mRNA and protein levels. However, relative to other
      tissues, the longest variant mRNA expression was predominant in the ovary and
      abundant in embryos. During embryogenesis, total tpk transcripts increased
      abruptly in early development, and decreased to about half of the peak shortly
      after hatching. In rainbow trout, the tpk transcript complex is ubiquitously
      expressed for all tissues and cells examined, and its increase in expression
      could be important in the early-middle embryonic stages. Moreover, decimated tpk
      expression in a hepatoma cell line relative to hepatic and gonadal cell lines
      appears to be consistent with previously reported down-regulation of thiamin
      metabolism in cancer.

PMID- 22659054
TI  - Infrared pupillometry to detect the light reflex during cardiopulmonary
      resuscitation: a case series.
AB  - BACKGROUND: The presence or absence of the pupillary light reflex following
      cardiopulmonary resuscitation has been shown to have prognostic value. We asked
      whether the light reflex could be objectively measured during cardiopulmonary
      resuscitation in humans and whether the quality of the reflex was associated with
      outcome. METHODS: Sixty-seven in-hospital code blue alerts were attended of which
      30 met our inclusion criteria. Portable infrared pupillometry was used to measure
      the light reflex during each code. The reliability of the presence of the light
      reflex during each code as a predictor of survival and neurological outcome was
      analyzed statistically using the Barnard's Exact test. RESULTS: In 25 patients
      (83%) the pupillary light reflex was detectable throughout or during a part of
      the resuscitation. Continuous presence of the light reflex or absence for less
      than 5 min during resuscitation was associated with early survival of the code
      and a good neurological outcome. In contrast, no patients without a light reflex
      or with a gradually deteriorating light reflex survived the code and absence of a
      pupillary light reflex for more than 5 min was associated with an unfavorable
      outcome. CONCLUSION: Portable infrared pupillary measurements can reliably
      demonstrate the presence and quality of the pupillary light reflex after cardiac
      arrest and during resuscitation. In our limited case series, the presence of the
      pupillary light reflexes obtained in serial measurements during resuscitation was
      associated with early survival and a favorable neurological status in the
      recovery period.

PMID- 22659055
TI  - Bystander-initiated cardiopulmonary resuscitation can curb the deterioration of
      regional cerebral oxygen saturation on hospital arrival in patients with cardiac
      arrest.

PMID- 22659056
TI  - Is the current product safety assessment paradigm protective for epigenetic
      mechanisms?
AB  - INTRODUCTION: The emerging field of epigenetics has revealed a new layer of gene
      regulation that is only now being fully explored. Concomitant with the increase
      in our understanding of epigenetic regulation are questions as to the role
      environmental factors may play in altering the epigenome. As these correlations
      between epigenetic changes and toxicity are made, the natural next question is if
      the current safety assessment paradigm utilizing a no-observed-adverse-effect
      level (NOAEL) is protective of public health for an epigenetic mechanism.
      METHODS: To begin to answer this question, several case studies were examined
      where apical end point dose response curves were compared to dose response data
      on epigenetic end points for 1,3-butadiene, arsenic, and diethylstilbesterol.
      RESULTS: This limited examination of the available literature for these three
      molecules revealed that epigenetic alterations largely fell within the dose
      response curve for apical effects. Perhaps more importantly, this analysis also
      revealed some key data gaps that should be addressed such as incongruent study
      designs and limited epigenetic dose response data for only a small subset of
      known epigenetic marks. Taken together, the answer to the question of whether the
      current product safety assessment paradigm is protective of epigenetic
      alterations is "yes, based on our current understanding of epigenetics". That is,
      this paradigm would be protective of any mechanism that resulted in adverse
      effects typically observed in guideline studies, because product safety
      assessment is based upon observed apical effects to drive an overall NOAEL that
      is the basis to set reference doses for a risk assessment. DISCUSSION: These
      adverse apical effects are the culmination of all molecular events, regardless of
      mechanism and may include alterations in the epigenome secondary to the actions
      of those mechanism(s). The epigenome is in a constant state of flux throughout
      cellular growth and development, and this dynamic variability is not completely
      characterized. Thus given the state of our current scientific understanding, a
      change in itself cannot be contextualized as adverse in the absence of a
      phenotypic anchor. Clearly, more research is needed in this area to perform
      additional epigenetic studies that include apical end points with full dose
      response curves in order to gain a more comprehensive understanding of adverse
      health outcomes that could be causally linked to epigenetic changes.

PMID- 22659057
TI  - Optimising conditions for studying the acute effects of drugs on indices of
      cardiac contractility and on haemodynamics in anaesthetized guinea pigs.
AB  - INTRODUCTION: Detecting adverse effects of drugs on cardiac contractility is
      becoming a priority in pre-clinical safety pharmacology. The aim of this work was
      to optimise conditions and explore the potential of using the anaesthetized
      guinea pig as an in vivo model. METHODS: Guinea pigs were anaesthetized with
      Hypnorm/Hypnovel, isoflurane, pentobarbital or fentanyl/pentobarbital. The
      electrocardiogram (ECG), heart rate, arterial blood pressure and indices of
      cardiac contractility were recorded. In further experiments in
      fentanyl/pentobarbital anaesthetized guinea pigs the influence of bilateral
      versus unilateral carotid artery occlusion on haemodynamic responses was
      investigated and the effects of inotropic drugs on left ventricular (LV)
      dP/dt(max) and the QA interval were determined. RESULTS: Pentobarbital, given
      alone or after fentanyl, provided suitable anaesthesia for these experiments.
      Bilateral carotid artery occlusion did not alter heart rate or arterial blood
      pressure responses to isoprenaline or angiotensin II. Isoprenaline and ouabain
      increased LVdP/dt(max) and decreased the QA interval whereas verapamil had
      opposite effects and strong inverse correlations between LVdP/dt(max) and the QA
      interval were found. DISCUSSION: Conditions can be optimised to allow the
      pentobarbital-anaesthetized guinea pig to be used for simultaneous measurement of
      the effects of drugs on the ECG, haemodynamics and indices of cardiac
      contractility. The use of this small animal model in early pre-clinical safety
      pharmacology should contribute to improvements in detecting unwanted actions on
      the heart during the drug development process.

PMID- 22659058
TI  - Gamma-glutamyltransferase, alanine transaminase and aspartate transaminase levels
      and the diagnosis of gestational diabetes mellitus.
AB  - OBJECTIVES: To evaluate gamma-glutamyltransferase (GGT), alanine transaminases
      (ALT) and aspartate transaminases (AST) levels and prevalent gestational diabetes
      mellitus (GDM). DESIGN AND METHODS: Random plasma glucose, GGT, ALT and AST and
      the 50-g glucose challenge test were done on antenatal women followed by
      diagnostic 3-point 75-g oral glucose tolerance test within two weeks. GDM was
      diagnosed by ADA (2011) criteria. RESULTS: The GDM rate was 12.2% (319/2610).
      Mean GGT level was higher in GDM women, 18 +/- 12 vs. 16 +/- 11 IU/L; P=0.03. The
      risk for GDM was higher for women in the highest GGT quartile band compared to
      the lowest: RR 1.35 95%CI 1.0-1.8; P=0.04. However, after adjustment for
      confounders, GGT was no longer associated with GDM. There was no correlation
      between ALT and AST levels and GDM. CONCLUSIONS: Liver transaminases do not
      predict GDM in contrast to type 2 diabetes.

PMID- 22659059
TI  - Impact of admission anemia, C-reactive protein and mean platelet volume on short
      term mortality in patients with acute ST-elevation myocardial infarction treated
      with primary angioplasty.
AB  - OBJECTIVES: To investigate admission anemia, C-reactive protein (CRP) and mean
      platelet volume (MPV) together as prognostic markers in ST-elevation myocardial
      infarction (STEMI). DESIGN AND METHODS: Baseline hemoglobin, CRP and MPV were
      determined in 543 patients with acute STEMI to whom primary angioplasty was
      performed and evaluated for short term mortality (30 days). RESULTS: After
      multivariate analysis anemia (odds ratio 2.69, 95% confidence interval 1.24-5.86)
      and CRP (odds ratio 3.40, 95% confidence interval 1.13-10.22) remained
      significant independent predictors of short-term mortality. Addition of anemia
      and CRP to PAMI risk score improved prediction of short-term outcome; area under
      ROC curve rose from 0.76 to 0.87 (p<0.001). CONCLUSION: Better ability to
      determine 30-day mortality was obtained when anemia and CRP were incorporated
      into the PAMI risk score.

PMID- 22659060
TI  - Compromising for carrier detection of beta thalassemia based on measurement of
      HbA2 levels in unusual cases.
AB  - BACKGROUND: An increased HbA2 level is the hallmark for identification of beta
      thalassemia carriers. However, in some carriers the level of HbA2 is not
      typically elevated creating difficulties in making a diagnosis. METHODS: We
      describe a family having an affected child referred to us for confirmation of
      diagnosis of beta thalassemia. RESULTS: The father has a classical beta
      thalassemia trait and the mother showed typical reduced red cell indices with a
      high RBC count but the HbA2 level was normal (2.4%). On molecular analysis she
      was a heterozygous carrier having IVS1 nt 5 (G->C) beta thalassemia mutation.
      Further analysis of delta globin gene showed that the reduction in HbA2 was due
      to the presence of the delta mutation HbA2 Pelendri [CD 141(Leu->Pro, CTG->CCG)].
      CONCLUSIONS: The diagnosis of a beta thalassemia carrier could have been
      compromised, and states the importance of comprehensive molecular analysis for
      accurate diagnosis in couples where one partner has beta thalassemia trait.

PMID- 22659061
TI  - Oxidized low-density lipoproteins and their antibodies: relationships with the
      reverse cholesterol transport and carotid atherosclerosis in adults without
      cardiovascular diseases.
AB  - BACKGROUND: Metabolic predictors and the atherogenicity of oxidized LDL (oxLDL)
      and the specific antibodies against oxLDL (oxLDL Ab) are unclear and
      controversial. METHODS: In 107 adults without atherosclerotic manifestations, we
      measured oxLDL and oxLDL Ab, and also the activities of CETP, PLTP, lipases and
      the carotid intima-media thickness (cIMT). Comparisons were performed for the
      studied parameters between the lowest and the highest tertile of oxLDL and oxLDL
      Ab, and the relationships between studied variables were evaluated. RESULTS:
      Subjects with higher oxLDL Ab present reduced hepatic lipase activity and
      borderline increased cIMT. In the highest oxLDL tertile, besides the higher
      levels of total cholesterol, LDL-C and apoB100, we found reduced CETP activity
      and higher cIMT. A significant correlation between oxLDL Ab and cIMT, independent
      of oxLDL, and a borderline correlation between oxLDL and cIMT independent of
      oxLDL Ab were found. In the multivariate analysis, apoAI was a significant
      predictor of oxLDL Ab, in contrast to regulation of oxLDL by apoB100, PLTP and
      inverse of CETP. CONCLUSIONS: In adults without atherosclerotic disease, the
      metabolic regulation and carotid atherosclerosis of oxLDL Ab and oxLDL groups,
      characterized a dual trait in oxLDL Ab, as a contributor to carotid
      atherosclerosis, much less so than oxidized LDL, and with a modest
      atheroprotective role.

PMID- 22659063
TI  - Concordant chemical reaction networks.
AB  - We describe a large class of chemical reaction networks, those endowed with a
      subtle structural property called concordance. We show that the class of
      concordant networks coincides precisely with the class of networks which, when
      taken with any weakly monotonic kinetics, invariably give rise to kinetic systems
      that are injective - a quality that, among other things, precludes the
      possibility of switch-like transitions between distinct positive steady states.
      We also provide persistence characteristics of concordant networks, instability
      implications of discordance, and consequences of stronger variants of
      concordance. Some of our results are in the spirit of recent ones by Banaji and
      Craciun, but here we do not require that every species suffer a degradation
      reaction. This is especially important in studying biochemical networks, for
      which it is rare to have all species degrade.

PMID- 22659064
TI  - Photothermal microscopy of the core of dextran-coated iron oxide nanoparticles
      during cell uptake.
AB  - A detailed understanding of cellular interactions with superparamagnetic iron
      oxide nanoparticles (SPIONs) is critical when their biomedical applications are
      considered. We demonstrate how photothermal microscopy can be used to follow the
      cellular uptake of SPIONs by direct imaging of the iron oxide core. This offers
      two important advantages when compared with current strategies employed to image
      magnetic cores: first, it is nondestructive and is therefore suitable for studies
      of live cells and, second, it offers a higher sensitivity and resolution, thus
      allowing for the identification of low levels of SPIONs within a precise
      subcellular location. We have shown that this technique may be applied to the
      imaging of both cell monolayers and cryosections. In the former we have
      demonstrated the role of temperature on the rate of endocytosis, while in the
      latter we have been able to identify cells labeled with SPIONs from a mixed
      population containing predominantly unlabeled cells. Direct imaging of the SPION
      core is of particular relevance for research involving clinically approved
      SPIONs, which do not contain fluorescent tags and therefore cannot be detected
      via fluorescence microscopy.

PMID- 22659062
TI  - Childhood adversity increases vulnerability for behavioral symptoms and immune
      dysregulation in women with breast cancer.
AB  - Women respond differentially to the stress-associated with breast cancer
      diagnosis and treatment, with some women experiencing more intense and/or
      sustained behavioral symptoms and immune dysregulation than others. Childhood
      adversity has been identified to produce long-term dysregulation of stress
      response systems, increasing reactivity to stressors encountered during
      adulthood. This study determined whether childhood adversity increased
      vulnerability for more intense and sustained behavioral symptoms (fatigue,
      perceived stress, and depressive symptoms), poorer quality of life, and greater
      immune dysregulation in women (N=40) with breast cancer. Evaluation was after
      breast surgery and through early survivorship. Hierarchical linear modeling was
      used to examine intra-individual and inter-individual differences with respect to
      initial status and to the pattern of change (i.e. trajectory) of outcomes. At
      initial assessment, women exposed to childhood emotional neglect/abuse had
      greater perceived stress, fatigue, depressive symptoms and poorer quality of
      life, as well as lower natural killer cell activity (NKCA). Although these
      outcomes improved over time, women with greater childhood emotional neglect/abuse
      exhibited worse outcomes through early survivorship. No effect was observed on
      the pattern of change for these outcomes. In contrast, childhood physical neglect
      predicted sustained trajectories of greater perceived stress, worse quality of
      life, and elevated plasma IL-6; with no effect observed at initial assessment.
      Thus, childhood adversity leaves an enduring imprint, increasing vulnerability
      for behavioral symptoms, poor quality of life, and elevations in IL-6 in women
      with breast cancer. Further, childhood adversity predisposes to lower NKCA at a
      critical time when this immune-effector mechanism is most effective at halting
      nascent tumor seeding.

PMID- 22659065
TI  - Development and evaluation of a novel reverse transcription loop-mediated
      isothermal amplification (RT-LAMP) assay for detection of type II porcine
      reproductive and respiratory syndrome virus.
AB  - The objective of this study was to develop a reverse transcription loop-mediated
      isothermal amplification (RT-LAMP) assay for detection of type II porcine
      reproductive and respiratory syndrome virus (PRRSV). Based on sequence alignment,
      four primers were designed amplifying the M gene of type II PRRSV and were
      subsequently utilized in an RT-LAMP assay. The RT-LAMP product had a ladder-like
      pattern of bands and the optimal reaction condition for this assay was determined
      to be 40 min at 63 degrees C. Comparative analysis indicated that the RT-LAMP
      method was more sensitive than a conventional RT-PCR assay and comparable to a
      real-time PCR assay. In addition, the RT-LAMP assay was capable of detecting type
      II PRRSV in field samples and differentiating type II PRRSV from seven other
      porcine viruses which are all associated frequently with similar clinical
      symptoms.

PMID- 22659066
TI  - Monitoring the susceptibility to oseltamivir of Influenza A(H1N1) 2009 virus by
      nested-PCR and pyrosequencing during the pandemic and in the season 2010-2011.
AB  - For the early detection of the H275Y mutation as a marker of oseltamivir
      resistance in A(H1N1) pandemic strains, a sensitive and specific pyrosequencing
      assay was developed. This assay analyses a region 99nts long, encompassing the
      H275Y site, amplified by a nested PCR. Seventy-five respiratory specimens,
      obtained from 62 patients during the pandemic and in the 2010-2011 influenza
      season, in Tuscany, were tested. Resistant strains were demonstrated in 10
      patients. In three other patients, resistant and sensitive variants were found.
      This pyrosequencing assay may be a useful method for monitoring the spread of
      resistant influenza H1N1 2009 strains.

PMID- 22659067
TI  - A simple and sensitive method for determining the strand orientation of single
      stranded viral genomes.
AB  - Determining the nature of the viral genome is one of the first steps in
      characterization of any new virus. However, in the case of viruses with a single
      stranded genome, it is not always simple to identify its orientation. In this
      study, a rapid, sensitive and simple PCR-based method is described to identify
      the strand orientation of single-stranded viral genomes. This method has been
      tested on the single-stranded DNA viruses, M13 and phiX174.

PMID- 22659068
TI  - Poliovirus separation from cell extracts using capillary electrophoresis:
      potential use in vaccine production and control?
AB  - Rapid assessment of the concentration of virus particles in a given sample
      remains a challenge. Modern separation methods, such as capillary
      electrophoresis, were proposed recently to study viruses and viral infection or
      to separate and characterize viral vaccines in a time-efficient manner. Even
      though capillary electrophoresis is much more rapid than traditional virological
      methods and has the advantages of automation, increased precision and
      reliability, it has the drawback of reduced sensitivity for low concentrations. A
      sensitivity improvement is then necessary in many cases for a successful
      application. However, to date, only highly purified viral samples were examined
      using capillary electrophoresis. The injection of larger sample volumes, followed
      by intra-capillary concentration, was used in this study for cell extracts.
      Poliovirus was successfully detected rapidly, without any laborious staining
      procedures and incubation times. The method is simple, fast, automatic, requires
      only minute amounts of samples and reagents, and no expensive dyes or biological
      reagents. Additionally, the method showed a potential for monitoring the viral
      load during growth and purification, with obvious prospects for the optimization
      of the variable and time-consuming virus propagation procedures. The results of
      this study provide a potential basis for the development of routine methods for
      viral particles analysis, irrespective of their infective properties. In the
      future, the capillary electrophoresis test could help study the relationship
      between the intact poliovirus particles and the D-antigenic properties of a viral
      suspension, or could represent a supplementary or alternative test for virus
      concentration and D-antigen assays during vaccine production.

PMID- 22659069
TI  - Bad neighbors: arsenic-induced tumor cells convert normal stem cells into a
      cancerous phenotype.

PMID- 22659070
TI  - Effectiveness of thermal and athermal short-wave diathermy for the management of
      knee osteoarthritis: a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the effectiveness of short-wave diathermy (SWD) treatment in
      the management of knee osteoarthritis (KOA) and to assess whether the effects are
      related to the induction of a thermal effect. METHODS: A systematic literature
      search was conducted in PubMed, CINAHL, PEDro, EMBASE, SPORTdiscus and Scholar
      Google. Included were trials that compared the use of SWD treatment in patients
      diagnosed with KOA with a control group (placebo SWD treatment or no
      intervention) and studies that used high-frequency electromagnetic energy (i.e.,
      27.12 MHz) with sufficient information regarding treatment dosage. Methodological
      quality of the included studies was assessed in accordance with the PEDro
      classification scale. A minimum of a 6/10 score was required for inclusion.
      RESULTS: Seven studies were included in the final analysis. Treatment protocols
      (dosage, duration, number of treatments) varied extensively between studies. The
      meta-analysis of the studies with low mean power did not favour SWD treatment for
      pain reduction, while the results of studies employing some thermal effect were
      significant. No treatment effect on functional performance measures was
      determined. CONCLUSION: This meta-analysis found small, significant effects on
      pain and muscle performance only when SWD evoked a local thermal sensation.
      However, the variability in the treatment protocols makes it difficult to draw
      definitive conclusions about the factors determining the effectiveness of SWD
      treatment. More research (using comparable protocols and outcome measurements) is
      needed to evaluate possible long-term effects of thermal SWD treatment and its
      cost effectiveness in patients with KOA.

PMID- 22659071
TI  - Haplotypes across the human caveolin 1 gene upstream purine complex significantly
      alter gene expression: implication in neurodegenerative disorders.
AB  - We have previously reported a polymorphic purine complex at the 1.5 kb upstream
      region of the human caveolin 1 (CAV1) gene that is conserved across several
      species in respect with sequence motifs and the location of the complex. The IRF
      and Ets transcription factors have common binding sites for this region across
      those species. We have also shown skew in the homozygote haplotype compartment of
      this complex in two neurodegenerative disorders, sporadic late-onset Alzheimer's
      disease (AD), and multiple sclerosis (MS), versus disease-free controls
      (p<0.0000001). In the current study, we analyze the functional implication of the
      disease homozygote haplotypes (i.e. 102-bp and 142-bp) vs. control homozygote
      haplotype (110-bp) in three neuronal cell lines, LAN-5, U-87 MG, and N2A, using
      dual luciferase reporter system. A significant increase in gene expression was
      observed in the cell lines with the disease haplotype constructs vs. control
      haplotype in the three cell lines (t-test p<4 * 10(-4), 1 * 10(-6), and 3 * 10(
      4)), respectively. We conclude that the human CAV1 upstream purine complex
      modifies gene expression. An additive effect of the haplotypes in the homozygous
      status is speculated based on the skew in the homozygote haplotypes in
      neurodegenerative disorders.

PMID- 22659073
TI  - Comparison in the biological characteristics between primary cultured sensory and
      motor Schwann cells.
AB  - Schwann cells (SCs) express distinct sensory and motor phenotypes, which are
      associated with modality-specific promotion of axon growth. Here we compared cell
      proliferation and migration of primary cultured sensory and motor SCs and
      determined the mRNA expression of several genes, nap1l1, dok4, lpp, mmp-9 and
      l1cam, in two phenotypes of SCs. The results showed that the rate of cell
      proliferation or migration was higher in sensory SCs than in motor SCs, and the
      five proliferation or migration-related genes also had higher expression in
      sensory SCs than in motor SCs. These findings may provide a basis for deeply
      studying the biological differences between sensory and motor SCs.

PMID- 22659072
TI  - CBT4BN versus CBTF2F: comparison of online versus face-to-face treatment for
      bulimia nervosa.
AB  - Cognitive-behavioral therapy (CBT) is currently the "gold standard" for treatment
      of bulimia nervosa (BN), and is effective for approximately 40-60% of individuals
      receiving treatment; however, the majority of individuals in need of care do not
      have access to CBT. New strategies for service delivery of CBT and for maximizing
      maintenance of treatment benefits are critical for improving our ability to treat
      BN. This clinical trial is comparing an Internet-based version of CBT (CBT4BN) in
      which group intervention is conducted via therapeutic chat group with traditional
      group CBT (CBTF2F) for BN conducted via face-to-face therapy group. The purpose
      of the trial is to determine whether manualized CBT delivered via the Internet is
      not inferior to the gold standard of manualized group CBT. In this two-site
      randomized controlled trial, powered for non-inferiority analyses, 180
      individuals with BN are being randomized to either CBT4BN or CBTF2F. We
      hypothesize that CBT4BN will not be inferior to CBTF2F and that participants will
      value the convenience of an online intervention. If not inferior, CBT4BN may be a
      cost-effective approach to service delivery for individuals requiring treatment
      for BN.

PMID- 22659074
TI  - Uptake of lithium into rat brain after acute and chronic administration.
AB  - Lithium is licensed for the treatment of bipolar disorders and also discussed in
      relation to neuroprotective properties. Although the drug has a small therapeutic
      window, its uptake and passage into the brain are poorly understood. We
      administered lithium to rats, following an acute (3 mmol/kg, i.p.) or chronic (3
      mmol/kg/day, p.o.) regime. Lithium levels were assessed in serum, brain
      homogenate, cerebrospinal fluid (CSF) and, by means of microdialysis, in the
      extracellular space (ECS) of the brain 2, 6 and 24h post injection or after 3
      weeks of chronic administration. Lithium is detected in brain ECS within minutes
      of administration and reaches maximum levels in brain extracellular fluid after
      30 min. In the early phase after lithium administration (2 and 6h), serum levels
      of lithium do not differ significantly from those assessed in CSF and brain
      homogenate. Afterwards, however, accumulation in brain tissue occurs. As a
      consequence, after 24h and 3 weeks, lithium levels in brain homogenate (i.e.,
      intracellular levels) are significantly higher than in CSF or dialysates (i.e.,
      extracellular levels). In conclusion, lithium rapidly reaches the brain, but
      after prolonged treatment, brain intracellular levels are high and poorly
      represented by plasma or CSF measurements.

PMID- 22659075
TI  - Association of the miR-146aC>G, miR-196a2C>T, and miR-499A>G polymorphisms with
      moyamoya disease in the Korean population.
AB  - Recent evidence has demonstrated associations between the single nucleotide
      polymorphism (SNP) rs11614913 in miR-196a2C>T and various pathologies. A main
      target of miRNA-196a is annexin A1 (lipocortin1, ANXA1), which is associated with
      increased multiple malignant tumors in brain models of ischemia and reperfusion
      injury. To determine the effects of miRNA SNPs in moyamoya disease, we recruited
      107 patients with moyamoya disease and 240 healthy controls from a Korean study
      population and determined the genotype of each participant from whole blood
      samples. We compared the patient and the control genotypes and allele frequencies
      of rs2910164, rs11614913, and rs3746444 and investigated the association of the
      three SNPs with age and clinical characteristics, such as cerebral hemorrhage or
      infarction. rs11614913 in miR-196a2C>T was significantly associated with moyamoya
      disease. The association of this SNP with adult age and cerebral infarction was
      statistically significant compared to the control group, but the association with
      hemorrhagic moyamoya disease was not significant. The CT+CC genotype of miR-196a2
      was represented at an increased frequency among patients with moyamoya disease.
      However, the distribution of miR-146aC>G and miR-499A>G genotypes was not
      statistically different between participants who were healthy and those with
      moyamoya disease. Thus, the SNP rs11614913 is significantly associated with
      moyamoya disease, as well as cerebral infarction and adult age in patients with
      moyamoya disease. This study demonstrates a higher frequency of the CT+CC
      genotype of the SNP rs11614913 in miR-196a2C>T, which suggests that miR-196a2 may
      play a role in the pathogenesis of moyamoya disease.

PMID- 22659076
TI  - Paraoxonase 1 (PON1) as a marker of short term death in breast cancer recurrence.
AB  - OBJECTIVE: To relate paraoxonase (PON1) activity to survival time and short term
      death in breast cancer recurrence. DESIGN AND METHODS: PON1 activity was measured
      by its rate of hydrolysis of two different substrates, paraoxon (PON) and
      phenylacetate (ARE) in 50 patients with recurrence of breast cancer. Results were
      compared between patients surviving more than one year after the analysis (22)
      and those who died within one year (28). RESULTS: In a logistic regression
      analysis, ARE was negatively associated with early death (OR=0.10 [0.02-0.58],
      p=0.0109). PON did not reach significance (OR=0.43 [0.17-1.11], p=0.0826). In a
      multiple logistic regression analysis model, ARE was independently associated
      with early death (OR=0.12 [0.02-0.98], p=0.0476), besides interval time between
      diagnosis and recurrence (OR=0.54 [0.27-1.07], p=0.0781) and undernutrition
      (OR=3.95 [0.81-19.19], p=0.0883). CONCLUSION: Paraoxonase is a potential marker
      of survival in patients with breast cancer recurrence.

PMID- 22659077
TI  - Overprotective parenting and child anxiety: the role of co-occurring child
      behavior problems.
AB  - The relationship between overprotective parenting and child anxiety has been
      examined repeatedly because theories emphasize its role in the maintenance of
      child anxiety. No study has yet tested whether this relationship is unique to
      child anxiety, by controlling for commonly co-occurring behavior problems within
      the same children. The current study examined 190 children (age 7-13, 118
      [corrected] boys) referred to mental health clinics and their parents. Results
      revealed that significant correlations between overprotective parenting and child
      anxiety symptoms disappear after controlling for co-occurring child behavior
      symptoms. It appears that overprotection is not uniquely related to child
      anxiety. Furthermore, overprotective parenting was significantly and uniquely
      related to child behavior symptoms. Researchers and practitioners need to
      consider co-occurring child behavior problems when working with the parents of
      anxious children.

PMID- 22659078
TI  - Brief internet-delivered cognitive behavioral therapy for anxiety in older
      adults: a feasibility trial.
AB  - This study examined the efficacy of an Internet-delivered cognitive-behavior
      therapy program developed for older adults. Twenty-two participants with elevated
      scores (>=8) on the Generalized Anxiety Disorder 7-Item Scale (GAD-7)
      participated in the course, which consisted of five lessons, homework tasks,
      additional resources, a moderated discussion forum, and weekly telephone support
      from a Clinical Psychologist. Ninety-five percent of the sample met diagnostic
      criteria for an anxiety disorder at pre-treatment. All participants completed the
      five lessons within the allotted eight weeks. Three-month follow-up data was
      collected from 95% of participants. Reductions in symptoms of anxiety and stress,
      with large within-group effect sizes (Cohen's d) were found on the GAD-7 (d=1.03)
      and the Depression, Anxiety and Stress Scales - 21 Items (d=0.98) at follow-up.
      Participants reported high levels of satisfaction with the program. These
      encouraging results provide tentative support for the online treatment of older
      adults with anxiety.

PMID- 22659079
TI  - Casting a wider net: the quest for better guidance on seafood consumption.

PMID- 22659080
TI  - Equarin is involved as an FGF signaling modulator in chick lens differentiation.
AB  - Lens growth involves the proliferation of epithelial cells, followed by their
      migration to the equator region and differentiation into secondary fiber cells.
      It is widely accepted that fibroblast growth factor (FGF) signaling is required
      for the differentiation of lens epithelial cells into crystallin-rich fibers, but
      this signaling is insufficient to induce full differentiation. To better
      understand lens development, investigatory and functional analyses of novel
      molecules are required. Here, we demonstrate that Equarin, which is a novel
      secreted molecule, was expressed exclusively in the lens equator region during
      chick lens development. Equarin upregulated the expression of fiber markers, as
      demonstrated using in ovo electroporation. In a primary lens cell culture,
      Equarin promoted the biochemical and morphological changes associated with the
      differentiation of lens epithelial cells to fibers. A loss-of-function analysis
      was performed using zinc-finger nucleases targeting the Equarin gene. Lens cell
      differentiation was markedly inhibited when endogenous Equarin was blocked,
      indicating that Equarin was essential for normal chick lens differentiation.
      Furthermore, biochemical analysis showed that Equarin directly bound to FGFs and
      heparan sulfate proteoglycan and thereby upregulated the expression of phospho
      ERK1/2 (ERK-P) proteins, the downstream of the FGF signaling pathway, in vivo and
      in vitro. Conversely, the absence of endogenous Equarin clearly diminished FGF
      induced fiber differentiation. Taken together, our results suggest that Equarin
      is involved as an FGF modulator in chick lens differentiation.

PMID- 22659081
TI  - Early patterning of cloned mouse embryos contributes to post-implantation
      development.
AB  - Several research groups have suggested that the embryonic-abembryonic (Em-Ab)
      axis in the mouse can be predicted by the first cleavage plane of the early
      embryo. Currently, it is not known whether this early patterning occurs in cloned
      embryos produced by nuclear transfer and whether it affects development to term.
      In this work, the relationship between the first cleavage plane and the Em-Ab
      axis was determined by the labeling of one blastomere in cloned mouse embryos at
      the 2-cell stage, followed by ex-vivo tracking until the blastocyst stage. The
      results demonstrate that approximately half of the cloned blastocysts had an Em
      Ab axis perpendicular to the initial cleavage plane of the 2-cell stage. These
      embryos were classified as "orthogonal" and the remainder as "deviant".
      Additionally, we report here that cloned embryos were significantly more often
      orthogonal than their naturally fertilized counterparts and overexpressed Sox2.
      Orthogonal cloned embryos demonstrated a higher rate of post-implantation
      embryonic development than deviant embryos, but cloned pups did not all survive.
      These results reveal that the angular relationship between the Em-Ab axis and the
      first cleavage plane can influence later development and they support the
      hypothesis that proper early patterning of mammalian embryos is required after
      nuclear transfer.

PMID- 22659082
TI  - Differential distribution of compound microsatellites in various Human
      Immunodeficiency Virus Type 1 complete genomes.
AB  - Compound microsatellites consist of two or more individual microsatellites, and
      may originate from dynamic mutations or imperfection of microsatellites. Previous
      studies have found microsatellites were present in 81 completed Human
      Immunodeficiency Virus Type 1 (HIV-1) genomes, suggesting compound
      microsatellites may exist in viral genomes. However, up to now, compound
      microsatellites have not been analyzed in any viral genomes. We identified and
      characterized 238 compound microsatellites in 81 completed HIV-1 genomes. About 0
      24.24% of all microsatellites could be categorized as compound microsatellites.
      Compound microsatellite distribution is very different in two aspects between
      diverse HIV-1 genomes. First, the number and motifs of compound microsatellites
      are variable between surveyed genomes. Second, the relative abundance and
      relative density of compound microsatellites exhibit very significant differences
      between these surveyed genomes, respectively. The relative abundance and relative
      density of compound microsatellites were weakly correlated with genome size and
      microsatellite density. We observed a more dynamic picture of compound
      microsatellites than previously reported in eukaryotes. This might be attributed
      to the lack of proofreading in HIV-1 genomes, as it has been demonstrated that
      the loss of polymerase proofreading activity can greatly enhance the mutation
      rate of microsatellites.

PMID- 22659083
TI  - Application of metal-coded affinity tags (MeCAT): absolute protein quantification
      with top-down and bottom-up workflows by metal-coded tagging.
AB  - As the quantification of peptides and proteins extends from comparative analyses
      to the determination of actual amounts, methodologies for absolute protein
      quantification are desirable. Metal-coded affinity tags (MeCAT) are chemical
      labels for peptides and proteins with a lanthanide-bearing chelator as a core.
      This modification of analytes with non-naturally occurring heteroelements adds
      the analytical possibilities of inductively coupled plasma mass spectrometry
      (ICPMS) to quantitative proteomics. We here present the absolute quantification
      of recombinantly expressed aprotinin out of its host cell protein background
      using two independent MeCAT methodologies. A bottom-up strategy employs labeling
      of primary amino groups on peptide level. Synthetic peptides with a MeCAT label
      which are externally quantified by flow injection analysis (FIA)-ICPMS serve as
      internal standard in nanoHPLC-ESI-MS/MS. In the top-down approach, protein is
      labeled on cysteine residues and separated by two-dimensional gel
      electrophoresis. Flow injection analysis of dissolved gel spots by ICPMS yields
      the individual protein amount via its lanthanide label content. The enzymatic
      determination of the fusion protein via its beta-galactosidase activity found 8.3
      and 9.8 ng/MUg (nanogram fusion protein per microgram sample) for batches 1 and
      2, respectively. Using MeCAT values of 4.0 and 5.4 ng/MUg are obtained for top
      down analysis, while 14.5 and 15.9 ng/MUg were found in the bottom-up analysis.

PMID- 22659085
TI  - Energy depletion in seizures: anaplerosis as a strategy for future therapies.
AB  - Seizure activity can lead to energy failure and neuronal injury, resulting in
      neurological and cognitive sequelae. Moreover, mutations affecting genes encoding
      for proteins that maintain energy homeostasis within the cell often result in an
      epileptic phenotype, implying that energy failure can contribute to
      epileptogenesis. Indeed, there is evidence to indicate that the efficacy of the
      ketogenic diet, a treatment for refractory epilepsy, can be partly explained by
      its effect on increasing energetic substrates. The ATP level, reflecting the
      energy level of a cell, is maintained by the potential gradient across the
      mitochondrial membrane. This potential gradient is maintained by NADH/H(+)
      equivalents, produced by reactions within the tricarboxylic acid cycle (TCA
      cycle). Anaplerosis, the replenishment of TCA-cycle substrates, therefore
      represents an appealing strategy to address energy failure such as occurs in
      seizures. There is accumulating evidence that pyruvate, a classical anaplerotic
      substrate, has seizure suppressive effects and protects against seizure induced
      cell death. This review summarizes the evidence for the contribution of TCA cycle
      deficits in generating seizures. We highlight the role for TCA substrate
      supplementation in protecting against seizures and seizure induced cell death,
      and propose that these are important targets for future translational research
      addressing energy depletion in seizures. This article is part of the Special
      Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.

PMID- 22659084
TI  - Activation of ATP-sensitive potassium channels as an element of the
      neuroprotective effects of the Traditional Chinese Medicine MLC901 against oxygen
      glucose deprivation.
AB  - NeuroAid (MLC601 and MLC901), a Traditional Medicine used in China for patients
      after stroke has been reported in preclinical models of ischemia to induce
      neuroprotection and neuroplasticity. This work shows the effects of MLC901 on an
      in vitro model of oxygen glucose deprivation (OGD). MLC901 prevents neuronal
      death induced by 120 min OGD and decreases the exaggerated Ca2+ entry in mature
      cortical neurons exposed to 120 min OGD. The neuroprotective effect of MLC901 is
      associated with a large hyperpolarization of ~20 mV which is antagonized by
      glibenclamide, the specific inhibitor of K(ATP) channels. In addition MLC901
      strengthens the activation of K(ATP) channels. MLC901 has been directly shown to
      act as an activator of K(ATP) channels as potent as the classical K(ATP) channel
      opener. The capacity of MLC901 to produce a large hyperpolarization, particularly
      in neurons that have suffered from energy deprivation probably plays an important
      role in the neuroprotective effects of this traditional medicine that comes in
      addition to its previously demonstrated neuroregenerative properties.

PMID- 22659086
TI  - Cannabidiol administration after hypoxia-ischemia to newborn rats reduces long
      term brain injury and restores neurobehavioral function.
AB  - Cannabidiol (CBD) demonstrated short-term neuroprotective effects in the immature
      brain following hypoxia-ischemia (HI). We examined whether CBD neuroprotection is
      sustained over a prolonged period. Newborn Wistar rats underwent HI injury (10%
      oxygen for 120 min after left carotid artery electrocoagulation) and then
      received vehicle (HV, n = 22) or 1 mg/kg CBD (HC, n = 23). Sham animals were
      similarly treated (SV, n = 16 and SC, n = 16). The extent of brain damage was
      determined by magnetic resonance imaging, histological evaluation
      (neuropathological score, 0-5), magnetic resonance spectroscopy and Western
      blotting. Several neurobehavioral tests (RotaRod, cylinder rear test[CRT],and
      novel object recognition[NOR]) were carried out 30 days after HI (P37). CBD
      modulated brain excitotoxicity, oxidative stress and inflammation seven days
      after HI. We observed that HI led to long-lasting functional impairment, as
      observed in all neurobehavioral tests at P37, whereas the results of HC animals
      were similar to those of sham animals (all p < 0.05 vs. HV). CBD reduced brain
      infarct volume by 17% (p < 0.05) and lessened the extent of histological damage.
      No differences were observed between the SV and SC groups in any of the
      experiments. In conclusion, CBD administration after HI injury to newborn rats
      led to long-lasting neuroprotection, with the overall effect of promoting greater
      functional rather than histological recovery. These effects of CBD were not
      associated with any side effects. These results emphasize the interest in CBD as
      a neuroprotective agent for neonatal HI.

PMID- 22659087
TI  - Dopaminergic modulation of hippocampus-dependent learning: blockade of
      hippocampal D1-class receptors during learning impairs 1-trial place memory at a
      30-min retention delay.
AB  - Consistent with the requirement of D1-class dopamine receptors for the induction
      of late (>3 h) hippocampal long-term potentiation (LTP), hippocampus-dependent 1
      trial memory at long retention delays (>6 h) requires hippocampal D1-class
      receptors during learning. Hippocampal D1-class receptors also modulate the
      induction and magnitude of early LTP (<1-3 h). However, a corresponding
      modulation of the formation of hippocampus-dependent early (<1 h) memory remains
      to be revealed. We addressed this conceptually important issue, using a novel
      modification of the watermaze delayed-matching-to-place (DMP) test with an
      improved measure of hippocampus-dependent 1-trial place memory. On the DMP test,
      rats learn the novel location of a hidden escape platform on trial 1 of every
      day, so that 1-trial place memory can be measured on trial 2. Our new task
      modification includes the measurement of search preference for the correct
      location on trial 2 - a very sensitive index of hippocampus-dependent place
      memory. We examined the effects of hippocampal D1-class receptor blockade or
      stimulation during learning on memory at a 30-min retention delay. Bilateral
      hippocampal infusion of the D1-class receptor antagonist SCH23390 (1 or 5 MUg/1
      MUl/side) before trial 1 dose-dependently impaired such early memory: rats
      infused with the higher dose showed reduced search preference for the correct
      location and took longer paths to reach this location. Infusion of the D1-class
      partial agonist SKF38393 (1 or 5 MUg/1 MUl/side) did not affect measures of 1
      trial place memory. Our data reveal a behavioural correlate of the dopaminergic
      modulation of early LTP, thereby supporting the close correspondence between
      hippocampal LTP and hippocampus-dependent learning.

PMID- 22659088
TI  - The interaction between mGluR1 and the calcium channel Cav2.1 preserves coupling
      in the presence of long Homer proteins.
AB  - Group I metabotropic glutamate receptors (mGluR1 and 5) are G protein coupled
      receptors that regulate neuronal activity in a number of ways. Some of the most
      well studied functions of group I mGluRs, such as initiation of multiple forms of
      mGluR-dependent long-term depression, require receptor localization near the post
      synaptic density (PSD). This localization is in turn dependent on the Homer
      family of scaffolding proteins which bind to a small motif on the distal C
      termini of mGluR1 and 5, localize the receptors near the PSD, strengthen coupling
      to post-synaptic effectors and simultaneously uncouple the mGluRs from extra
      synaptic effectors such as voltage dependent ion channels. Here the selectivity
      of this uncoupling process was examined by testing the ability of Homer-2b to
      uncouple mGluR1 from multiple voltage dependent calcium channels including
      Ca(V2.2) (N-type), Ca(V3.2) (T-type), and Ca(V2.1) (P/Q-type) expressed in rat
      sympathetic neurons from the superior cervical ganglion (SCG). Of these, only the
      mGluR1-Ca(V2.1) modulatory pathway was insensitive to Homer-2b expression.
      Uncoupling from this channel was achieved by co-expression of an mGluR1 C
      terminal protein designed to disrupt a previously described direct interaction
      between these two proteins, suggesting that this interaction allows incorporation
      of Ca(V2.1) into the mGluR1/Homer signaling complex, thereby preserving
      modulation in the presence of scaffolding Homer proteins. This article is part of
      a Special Issue entitled 'Metabotropic Glutamate Receptors'.

PMID- 22659089
TI  - Inhibition of human astrocyte and microglia neurotoxicity by calcium channel
      blockers.
AB  - We examined the effects of L-type calcium channel blockers (CCBs) on toxicity
      exerted by activated human astrocytes and microglia towards SH-SY5Y human
      neuronal cells. The CCBs nimodipine (NDP) and verapamil (VPM) both significantly
      suppressed toxic secretions from human astrocytes and astrocytoma U-373 MG cells
      that were induced by interferon (IFN)-gamma. NDP also inhibited neurotoxic
      secretions of human microglia and monocytic THP-1 cells that were induced by the
      combination of lipopolysaccharide and IFN-gamma. In human astrocytes, both NDP
      and VPM reduced IFN-gamma-induced phosphorylation of signal transducer and
      activator of transcription (STAT) 3. They also inhibited the astrocytic
      production of IFN-gamma-inducible T cell alpha chemoattractant (I-TAC). These
      results suggest that CCBs attenuate IFN-gamma-induced neurotoxicity of human
      astrocytes through inhibition of the STAT3 signaling pathway. L-type CCBs,
      especially NDP, might be a useful treatment option for a broad spectrum of
      neurodegenerative diseases, including Alzheimer disease, where the pathology is
      believed to be exacerbated by neurotoxic glial activation.

PMID- 22659091
TI  - Genetic susceptibility to teratogens: state of the art.
AB  - There is evidence that the susceptibility to the teratogenic effect of drugs
      within human populations varies extremely from one individual to another, even
      after identical exposures. One of the factors that may explain these
      interindividual differences is the genetic makeup in the pharmacokinetics and
      pharmacodynamics of the respective drugs. In fact, both maternal and
      embryonic/fetal genotypes can affect placental transport, absorption, metabolism,
      distribution and receptor binding of an agent, influencing its teratogenicity. We
      have reviewed the literature and commented on the reported correlations between
      genetic factors and drug-induced birth defects. There is still a clear lack of
      knowledge regarding this issue and the available data are often conflicting.
      However, the identification of specific polymorphisms associated with
      predisposition to teratogenesis may allow in the future the development of
      personalized non-teratogenic therapies for pregnant women.

PMID- 22659090
TI  - Pharmacological profiling of native group II metabotropic glutamate receptors in
      primary cortical neuronal cultures using a FLIPR.
AB  - The group II metabotropic glutamate (mGlu) receptors comprised of the mGlu2 and
      mGlu3 receptor subtypes have gained recognition in recent years as potential
      targets for psychiatric disorders, including anxiety and schizophrenia. In
      addition to studies already indicating which subtype mediates the anxiolytic and
      anti-psychotic effects observed in disease models, studies to help further define
      the preferred properties of selective group II mGlu receptor ligands will be
      essential. Comparison of the in vitro properties of these ligands to their in
      vivo efficacy and tolerance profiles may help provide these additional insights.
      We have developed a relatively high-throughput native group II mGlu receptor
      functional assay to aid this characterisation. We have utilised dissociated
      primary cortical neuronal cultures, which after 7 days in vitro have formed
      functional synaptic connections and display periodic and spontaneous synchronised
      calcium (Ca(2+)) oscillations in response to intrinsic action potential bursts.
      We herein demonstrate that in addition to non-selective group II mGlu receptor
      agonists, (2R,4R)-APDC, LY379268 and DCG-IV, a selective mGlu2 agonist, LY541850,
      and mGlu2 positive allosteric modulators, BINA and CBiPES, inhibit the frequency
      of synchronised Ca(2+) oscillations in primary cultures of rat and mouse cortical
      neurons. Use of cultures from wild-type, mGlu2(-/-), mGlu3(-/-) and mGlu2/3(-/-)
      mice allowed us to further probe the contribution of mGlu2 and mGlu3, and
      revealed LY541850 to be a partial mGlu2 agonist and a full mGlu3 antagonist.
      Overnight pre-treatment of cultures with these ligands revealed a preferred
      desensitisation profile after treatment with a positive allosteric modulator.
      This article is part of a Special Issue entitled 'Metabotropic Glutamate
      Receptors'.

PMID- 22659092
TI  - Role of human UDP-glucuronosyltransferases in the biotransformation of the
      triazoloacridinone and imidazoacridinone antitumor agents C-1305 and C-1311:
      highly selective substrates for UGT1A10.
AB  - 5-Diethylaminoethylamino-8-hydroxyimidazoacridinone, C-1311 (NSC-645809), is an
      antitumor agent shown to be effective against breast cancer in phase II clinical
      trials. A similar compound, 5-dimethylaminopropylamino-8
      hydroxytriazoloacridinone, C-1305, shows high activity against experimental
      tumors and is expected to have even more beneficial pharmacological properties
      than C-1311. Previously published studies showed that these compounds are not
      substrates for cytochrome P450s; however, they do contain functional groups that
      are common targets for glucuronidation. Therefore, the aim of this work was to
      identify the human UDP-glucuronosyltransferases (UGTs) able to glucuronidate
      these two compounds. High-performance liquid chromatography analysis was used to
      examine the activities of human recombinant UGT1A and UGT2B isoforms and
      microsomes from human liver [human liver microsomes (HLM)], whole human
      intestinal mucosa [human intestinal microsomes (HIM)], and seven isolated
      segments of human gastrointestinal tract. Recombinant extrahepatic UGT1A10
      glucuronidated 8-hydroxyl groups with the highest catalytic efficiency compared
      with other recombinant UGTs, V(max)/K(m) = 27.2 and 8.8 MUl . min-1 . mg protein
      1, for C-1305 and C-1311, respectively. In human hepatic and intestinal
      microsomes (HLM and HIM, respectively), high variability in UGT activities was
      observed among donors and for different regions of intestinal tract. However,
      both compounds underwent UGT-mediated metabolism to 8-O-glucuronides by
      microsomes from both sources with comparable efficiency; V(max)/K(m) values were
      from 4.0 to 5.5 MUl . min-1 . mg protein-1. In summary, these studies suggest
      that imid azoacridinone and triazoloacridinone drugs are glucuronidated in human
      liver and intestine in vivo and may form the basis for future translational
      studies of the potential role of UGTs in resistance to these drugs.

PMID- 22659093
TI  - Effects of chain microstructures on mechanical behavior and aging of a poly(L
      lactide-co-epsilon-caprolactone) biomedical thermoplastic-elastomer.
AB  - Three statistical poly(L-lactide-co-epsilon-caprolactone) (PLCL) copolymers of
      70% L-lactide content having different chain microstructures ranging from
      moderate blocky to random (R=0.47,0.69 and 0.92, respectively) were characterized
      by DSC, GPC and (1)H and (13)C NMR. The results demonstrate that higher
      randomness character (R->1) limits the capability of crystallization of LA-unit
      sequences shifting the melting temperature of the copolymers to lower values and
      reducing the crystallinity fraction substantially. The effect of different
      distributions of sequences of PLCL on crystallization and phase behavior was also
      studied for different storage times at room temperature (21+/-2 degrees C) by
      DSC. The mechanical properties were evaluated by tensile tests during aging. The
      PLCL showing a random character closest to the Bernoullian distribution of
      sequences (l(LA)=1/CL) was found to exhibit higher strain capability and strain
      recovery values and is less prone to supramolecular arrangements. However, as a
      result of aging, L-lactide sequence blocks in the other PLCLs of smaller
      randomness character tend to crystallize prompting to a double T(g) behavior
      indicative of the existence of phase separation into two compositionally
      different amorphous phases. Physical aging leads also to dramatic changes in
      tensile behavior of the moderate blocky PLCLs that evolved from being an
      elastomeric to be partly a glassy semicrystalline thermoplastic, and, thus, can
      eventually condition its potential uses for medical devices.

PMID- 22659094
TI  - C-H ... pi interplay between Ile308 and Tyr310 residues in the third repeat of
      microtubule binding domain is indispensable for self-assembly of three- and four
      repeat tau.
AB  - Information on the structural scaffold for tau aggregation is important in
      developing a method of preventing Alzheimer's disease (AD). Tau contains a
      microtubule binding domain (MBD) consisting of three or four repeats of 31 and 32
      similar residues in its C-terminal half. Although the key event in tau
      aggregation has been considered to be the formation of beta-sheet structures from
      a short hexapeptide (306)VQIVYK(311) in the third repeat of MBD, its aggregation
      pathway to filament formation differs between the three- and four-repeated MBDs,
      owing to the intermolecular and intramolecular disulphide bond formations,
      respectively. Therefore, the elucidation of a common structural element necessary
      for the self-assembly of three-/four-repeated full-length tau is an important
      research subject. Expanding the previous results on the aggregation mechanism of
      MBD, in this paper, we report that the C-H ... pi interaction between the Ile308
      and Tyr310 side chains in the third repeat of MBD is indispensable for the self
      assembly of three-/four-repeated full-length tau, where the interaction provides
      a conformational seed for triggering the molecular association. On the basis of
      the aggregation behaviours of a series of MBD and full-length tau mutants, a
      possible self-association model of tau is proposed and the relationship between
      the aggregation form (filament or granule) and the association pathway is
      discussed.

PMID- 22659095
TI  - Identification of substituted [3, 2-a] pyrimidines as selective antiviral agents:
      molecular modeling study.
AB  - A series of novel substituted dihydropyrimidine and 5H-thiazolo [3, 2-a]
      pyrimidine derivatives were designed and synthesized as a potential target to
      discover drugs fighting against the viral diseases. The main objective of the
      present work is to carry out the QSAR studies for all the series of the compounds
      starting from 4a to 6j to find out their molecular descriptors and predict the
      biological properties. All of them are showing the best QSAR descriptors, hence
      chosen for the prediction of anti-viral activity against Newcastle disease virus
      (NDV). Initially their inhibitory activity was predicted by molecular docking of
      these compounds against haemaglutinin-neuraminidase (HN) protein using molecular
      operating environment (MOE) software. Based on the best affinity and highest
      docking scores 4b, 5b and 6b were assayed in vivo on NDV infected chicks and it
      was found that there is significant improvement in the survival of the chicks
      with the treatment (P<0.05). 4b and 6b showed better curative effect than 5b at
      the dose concentration of 40 mg/kg body weight of chicks. The results from
      molecular docking study and biological assays can be inferred to consider these
      molecules as potential antiviral drugs.

PMID- 22659096
TI  - Laboratory investigations of the effects of geologic heterogeneity on groundwater
      salinization and flush-out times from a tsunami-like event.
AB  - This intermediate scale laboratory experimental study was designed to improve the
      conceptual understanding of aquifer flushing time associated with diffuse
      saltwater contamination of coastal aquifers due to a tsunami-like event. The
      motivation comes from field observations made after the tsunami in December, 2004
      in South Asia. The focus is on the role and effects of heterogeneity on flushing
      effectiveness. A scheme that combines experimentation in a 4.8m long laboratory
      tank and numerical modeling was used. To demonstrate the effects of geologic
      heterogeneity, plume migration and flushing times were analyzed in both
      homogeneous and layered media and under different boundary conditions (ambient
      flow, saltwater infiltration rate, freshwater recharge). Saltwater and freshwater
      infiltrations imitate the results of the groundwater salinization from the
      tsunami and freshening from the monsoon rainfall. The saltwater plume behavior
      was monitored both through visual observations (digital photography) of the dyed
      salt water and using measurements taken from several electrical conductivity
      sensors installed through the tank walls. The variable-density, three dimensional
      code HST3D was used to simulate the tank experiments and understand the fate and
      movement of the saltwater plume under field conditions. The results from the tank
      experiments and modeling demonstrated that macro-scale heterogeneity
      significantly influenced the migration patterns and flushing times of diffuse
      saltwater contamination. Ambient flow had a direct influence on total flush-out
      time, and heterogeneity impacted flush-out times for the top part of the tank and
      total flush-out times. The presence of a continuous low-permeability layer caused
      a 40% increase in complete flush-out time due to the slower flow of salt water in
      the low-permeability layer. When a relatively small opening was introduced in the
      low-permeability layer, salt water migrated quickly into a higher-permeable layer
      below causing a reduction in flush-out time. Freshwater recharge caused an early
      dilution of salt water in the top part of the tank in the case of a layered
      media, but also pushed the saltwater plume into the low-permeability layer which
      led to increased total flush-out times.

PMID- 22659097
TI  - Glucocorticoid-resistant asthma and novel anti-inflammatory drugs.
AB  - Synthetic glucocorticoids are among the most commonly used prescription
      medicines. Nevertheless, their clinical efficacy is accompanied by dose- and
      indication-limiting acute and chronic adverse effects. Intrinsic or acquired
      resistance to glucocorticoid actions may also limit clinical efficacy. In chronic
      inflammatory conditions there has been a considerable focus on understanding
      mechanism(s) of resistance in cells with a primary immune and/or inflammatory
      function. However, it has become increasingly accepted that a substantial part of
      the efficacy of glucocorticoid treatments derives from actions on 'structural'
      cell types (smooth muscle, fibroblasts, epithelia). In this article we review the
      mechanism of action of glucocorticoids on structural cells and contrast knowledge
      of resistance mechanisms between structural and inflammatory cell types, using
      asthma as an exemplar chronic inflammatory condition associated with
      glucocorticoid resistance.

PMID- 22659098
TI  - A minimalist fragment approach for the design of natural-product-like synthetic
      scaffolds.
AB  - Chemistry groups involved in drug discovery continue to devote their efforts to
      improving compound design with the aim of identifying new drug candidates. Many
      crucial factors must be considered, including: chemical stability, synthetic
      difficulty, chemical complexity and diversity, ADMET properties, cost, chemical
      novelty and intellectual property issues, and 'biological appropriateness'. With
      regard to the latter point, natural products offer an outstanding source of
      biologically active molecules that provide many useful features that enable us to
      design innovative, biologically biased, synthetic compounds. This article
      outlines the recent approaches in this area and suggests a simple metric to
      assess synthetic compounds for natural product likeness.

PMID- 22659099
TI  - Naive CD8 T cell activation by liver bone marrow-derived cells leads to a
      "neglected" IL-2low Bimhigh phenotype, poor CTL function and cell death.
AB  - BACKGROUND & AIMS: The occurrence of primary CD8 T cell activation within the
      liver, unique among the non-lymphoid organs, is now well accepted. However, the
      outcome of intrahepatic T cell activation remains controversial. We have
      previously reported that activation initiated by hepatocytes results in a
      tolerogenic phenotype characterized by low expression of CD25 and IL-2, poor
      cytotoxic T lymphocyte (CTL) function, and excessive expression of the pro
      apoptotic protein Bim. METHODS: To investigate whether this phenotype was due to
      activation in the absence of co-stimulation, we generated bone marrow (bm)
      radiation chimeras in which adoptively transferred naive transgenic CD8 T cells
      were activated in the presence of co-stimulation by liver bm-derived cells.
      RESULTS: Despite expressing pro-inflammatory cytokines, high levels of CD25 and
      CD54, donor T cells activated by liver bm-derived cells did not produce
      detectable IL-2 and displayed poor CTL function, suggesting incomplete
      acquisition of effector function. Simultaneously, these cells expressed high
      levels of Bim and died by neglect. Transfer of Bim-deficient T cells resulted in
      increased T cell numbers. CONCLUSIONS: These results imply that expression of
      CD25 and CD54 is co-stimulation dependent and distinguishes T cell activated by
      hepatocytes and liver bm-derived cells. In contrast, low expression of IL-2, poor
      CTL function and excess Bim production represent a more universal phenotype
      defining T cells undergoing primary activation by both types of hepatic antigen
      presenting cells (APC). These results have important implications for
      transplantation, in which all liver antigen presenting cells contribute to
      activation of T cells specific for the allograft.

PMID- 22659100
TI  - Highly potent binding and inverse agonist activity of bisphenol A derivatives for
      retinoid-related orphan nuclear receptor RORgamma.
AB  - The plastic chemical bisphenol A (BPA) has recently been suspected to be a base
      structure of endocrine disrupting chemicals, which achieve their adverse effects
      by interfering with human nuclear receptors. For instance, BPA, bisphenol AF, and
      tetrabromo- or tetrachloro-BPA (X4-BPA) have been characterized as binders for
      ERRgamma, ER, and PPARgamma, respectively. This ongoing string of findings has
      led to apprehension that some other BPA derivatives might also perturb important
      human nuclear receptors. The retinoid-related orphan receptor RORgamma has been
      strongly suspected to be a target of highly hydrophobic chemical substances
      because of its extreme affinity for lipophilic sterols. In the present study, we
      tested a series of BPA derivatives for their ability to bind to RORgamma, and
      identified two distinctly potent derivatives having isopropyl or sec-butyl groups
      at positions adjacent to the BPA-4-hydroxyl group. In particular, di-sec-butyl
      BPA has emerged as a considerably potent ligand (IC50)=146 nM). In the reporter
      gene assay, these compounds suppressed the basal constitutive transcriptional
      activity originally induced by wild-type RORgamma. The present results strongly
      suggested that RORgamma, and perhaps also RORalpha and RORbeta, binds highly
      hydrophobic and sterically hindered chemical substances, inducing some
      unspecified physiological and biochemical disruptions.

PMID- 22659101
TI  - Repeated intravenous infusion of human apolipoprotein(a) kringle V is associated
      with reversible dose-dependent acute tubulointerstitial nephritis without
      affecting glomerular filtration function.
AB  - Because anti-angiogenic agents have shown various toxicities in clinical
      applications, the determination of their toxicities and their reversibility is
      important in the design of clinical trials. This study was performed to
      investigate the potential toxicities of an angiogenesis inhibitor,
      apolipoprotein(a) (Apo(a)) kringle V (rhLK8) in rats. Rats administered an
      intravenous (IV) bolus injection of rhLK8 (200 mg/kg) for 7 days showed
      significant increases in serum blood urea nitrogen (BUN), creatinine and the
      BUN/creatinine ratio, which was compatible with acute tubulointerstitial
      nephritis (TIN) in pathological examination. Because anti-angiogenic therapies
      are usually based on long-term treatment strategies, rats were administered 200
      mg/kg/day of rhLK8 by intravenous infusion for 28 days. Rats receiving 200 mg/kg
      of rhLK8 showed abnormal serological and histologic findings, but their levels
      returned to within normal ranges 2 weeks after the cessation of administration.
      The creatinine clearance rate (CCr) was not affected by rhLK8 treatment.
      Collectively, our data indicate that the intravenous infusion of rhLK8 at
      therapeutic doses may induce renal toxicities, such as acute TIN, but these
      toxicities are clinically tolerable and reversible with close monitoring and a
      recovery period.

PMID- 22659102
TI  - Variations of human papillomavirus type 58 E6, E7, L1 genes and long control
      region in strains from women with cervical lesions in Liaoning province, China.
AB  - Infection with certain types of human papillomaviruses (HPVs) is a risk factor
      for the development of cervical cancer. HPV type 58 (HPV 58) is prevalent among
      Chinese women. The intratype sequence variants differ in oncogenic potential and
      their prevalences vary across geographic regions. The objective of this study was
      to analyze the variations of HPV 58 E6, E7, L1 genes and long control region
      (LCR) in a large samples collected from northeastern Chinese women with cervical
      lesions. A total of 2938 cervical samples were collected and tested for HPV type
      using a chip hybridization assay. The E6, E7, L1 genes and LCR of HPV 58 strains
      were amplified and the amplicons were subjected to direct nucleotide sequencing
      for variation identification. A total of 235 specimens were HPV 58 positive. High
      proportions of HPV 58 E6 (83.8%), E7 (76.7%), L1 (90.8%) genes and LCR (91.4%)
      variants were identified in strains from Chinese women. The most frequently
      observed variations were C307T (52.4%) in E6, T744G (74.9%) in E7, A6014C (56.9%)
      in L1 genes and C7266T, A7714G (55.2%) in LCR. For the E6 gene, nine nucleotide
      variations were identified. Among them, the A140G (T11A), A184C (E25D), G266C
      (V53L) and A313G were novel variations. Sequencing of the E7 gene revealed four
      typical nucleotide changes: G761A (G63D), G694A (G41R), T803C (V77A) and T744G.
      In the L1 gene, 39 nucleotide variations and 13 amino acid substitutions were
      identified. Among these mutations, 21 variations are reported here for the first
      time. Lineage A of HPV 58 was found in 142 of 174 strains (81.6%). The most
      prevalent HPV 58 variants in Chinese northeastern women belongs to lineage A.
      Novel variations in E6 and L1 genes were also reported. These findings provide
      new data regarding E6 and L1 gene variations of HPV 58 from women in northeast
      China.

PMID- 22659103
TI  - A compact exposure: estimating inhalation of engineered nanoparticles in cosmetic
      powders.

PMID- 22659104
TI  - First frozen repository for the Great Barrier Reef coral created.
AB  - To build new tools for the continued protection and propagation of coral from the
      Great Barrier Reef (GBR), an international group of coral and cryopreservation
      scientists known as the Reef Recovery Initiative joined forces during the
      November 2011 mass-spawning event. The outcome was the creation of the first
      frozen bank for Australian coral from two important GBR reef-building species,
      Acropora tenuis and Acropora millepora. Approximately 190 frozen samples each
      with billions of cells were placed into long-term storage. Sperm cells were
      successfully cryopreserved, and after thawing, samples were used to fertilize
      eggs, resulting in functioning larvae. Additionally, developing larvae were
      dissociated, and these pluripotent cells were cryopreserved and viable after
      thawing. Now, we are in a unique position to move our work from the laboratory to
      the reefs to develop collaborative, practical conservation management tools to
      help secure Australia's coral biodiversity.

PMID- 22659105
TI  - Vitreous preservation of articular cartilage from cryoinjury in rabbits.
AB  - Frozen osteoarticular grafts treated with liquid nitrogen are utilized for joint
      reconstruction after tumor resection, but the joints may subsequently develop
      osteoarthritic changes. To preserve articular cartilage from cryoinjury, we
      modified a vitrification method utilized for embryo cryopreservation and
      demonstrated in vitro that our vitrification protocol was effective for
      protecting cartilage from cryoinjury. In this study, we investigated in vivo
      whether this vitrification method could protect against osteoarthritic changes in
      articular cartilage. Osteochondral plugs were obtained from the distal femur of
      rabbits. These grafts were divided into 3 groups: Fresh group (F-group), non
      vitrification group (N-group), and vitrification group (V-group). After
      treatment, the plugs were re-implanted as autografts. Histological findings,
      chondrocyte viability, and ultrastructural examinations were examined 6, 12, and
      24weeks after implantation. Histological findings of chondrocytes for the V-group
      showed no significant difference from those of the F-group at any time point
      except at 24weeks postimplantation at the non-weight bearing site (p<0.05).
      Viability of chondrocyte showed no significant difference from those of the F
      group except at 12weeks postimplantation at the bearing site (p<0.05). In
      contrast, viable cells disappeared from the N-group and histology and viability
      significantly differed between the N-group and the V-group. Transmission electron
      microscopy demonstrated preservation of chondrocyte structure in the V-group and
      the F-group, but chondrocytes of the N-group were abnormally electron dense. Our
      vitrification method was effective in protecting chondrocytes from cryoinjury
      that might lead to cartilage degeneration. Reconstructing joints with
      osteoarticular grafts containing living cartilage may help to avert
      osteoarthritic changes. Our vitrification method could prove useful for
      reconstruction with frozen tumor-containing autografts and for long-term storage
      of living cartilage for allografts.

PMID- 22659106
TI  - Expression pattern of SVEP1 alternatively-spliced forms.
AB  - SVEP1 is a multi-domain protein recognized as a cell adhesion molecule (CAM). In
      this study, we focused on the activity regulation of an alternative promoter (AP)
      and the expression of alternative splice forms of mRNA from SVEP1 gene. The
      expression of SVEP1 isoforms was analyzed on RNA isolated from pre-osteoblastic
      MBA-15 and mammary adenocarcinoma DA3 cells grown alone or following co-culture
      between these cells. The co-culture system aimed to mimic the cellular cross talk
      that exists in the bone microenvironment once the mammary cells invade the bone.
      We demonstrated that SVEP1 isoforms were differentially expressed between these
      cells. The various isoforms levels were affected by co-culturing or in cells
      treated with TNFalpha or estrogen. Both cell lines exhibited an increase of
      message levels of a and e isoforms following the co-culture conditions. A novel
      aspect presented here is related to existence of an alternative promoter (AP) in
      SVEP1 gene. The AP was in silico predicted and analyzed for binding by specific
      transcription factors (TFIIB, ERalpha, NF-kappaB, Sp1 and pcJUN) using Chromatin
      immunoprecipitation (ChIP) assay. The binding of these TFs results in a non
      uniform binding pattern when comparing between the DA3 and MBA-15 cells. Using
      the demethylation agent, 5'-aza-deoxycitidine and histone deacetylase inhibitor,
      Trichostatin-A allowed to study the methylation level of the AP and the message
      expression. This study provides insights into alternative splice forms of SVEP1
      and their regulation that may play a role within the bone niche with invading
      carcinoma cells.

PMID- 22659107
TI  - Response of face-selective brain regions to trustworthiness and gender of faces.
AB  - Neuropsychological and neuroimaging studies have demonstrated a role for the
      amygdala in processing the perceived trustworthiness of faces, but it remains
      uncertain whether its responses are linear (with the greatest response to the
      least trustworthy-looking faces), or quadratic (with increased fMRI signal for
      the dimension extremes). It is also unclear whether the trustworthiness of the
      stimuli is crucial or if the same response pattern can be found for faces varying
      along other dimensions. In addition, the responses to perceived trustworthiness
      of face-selective regions other than the amygdala are seldom reported. The
      present study addressed these issues using a novel set of stimuli created through
      computer image-manipulation both to maximise the presence of naturally occurring
      cues that underpin trustworthiness judgments and to allow systematic manipulation
      of these cues. With a block-design fMRI paradigm, we investigated neural
      responses to computer-manipulated trustworthiness in the amygdala and core face
      selective regions in the occipital and temporal lobes. We asked whether the
      activation pattern is specific for differences in trustworthiness or whether it
      would also track variation along an orthogonal male-female gender dimension. The
      main findings were quadratic responses to changes in both trustworthiness and
      gender in all regions. These results are consistent with the idea that face
      responsive brain regions are sensitive to face distinctiveness as well as the
      social meaning of the face features.

PMID- 22659109
TI  - Automated semantic indices related to cognitive function and rate of cognitive
      decline.
AB  - The objective of our study is to introduce a fully automated, computational
      linguistic technique to quantify semantic relations between words generated on a
      standard semantic verbal fluency test and to determine its cognitive and clinical
      correlates. Cognitive differences between patients with Alzheimer's disease and
      mild cognitive impairment are evident in their performance on the semantic verbal
      fluency test. In addition to the semantic verbal fluency test score, several
      other performance characteristics sensitive to disease status and predictive of
      future cognitive decline have been defined in terms of words generated from
      semantically related categories (clustering) and shifting between categories
      (switching). However, the traditional assessment of clustering and switching has
      been performed manually in a qualitative fashion resulting in subjective scoring
      with limited reproducibility and scalability. Our approach uses word definitions
      and hierarchical relations between the words in WordNet((r)), a large electronic
      lexical database, to quantify the degree of semantic similarity and relatedness
      between words. We investigated the novel semantic fluency indices of mean
      cumulative similarity and relatedness between all pairs of words regardless of
      their order, and mean sequential similarity and relatedness between pairs of
      adjacent words in a sample of patients with clinically diagnosed probable (n=55)
      or possible (n=27) Alzheimer's disease or mild cognitive impairment (n=31). The
      semantic fluency indices differed significantly between the diagnostic groups,
      and were strongly associated with neuropsychological tests of executive function,
      as well as the rate of global cognitive decline. Our results suggest that word
      meanings and relations between words shared across individuals and
      computationally modeled via WordNet and large text corpora provide the necessary
      context to account for the variability in language-based behavior and relate it
      to cognitive dysfunction observed in mild cognitive impairment and Alzheimer's
      disease.

PMID- 22659110
TI  - Probabilistic classification learning with corrective feedback is selectively
      impaired in early Huntington's disease--evidence for the role of the striatum in
      learning with feedback.
AB  - In general, declarative learning is associated with the activation of the medial
      temporal lobes (MTL), while the basal ganglia (BG) are considered the substrate
      for procedural learning. More recently it has been demonstrated the distinction
      of these systems may not be as absolute as previously thought and that not only
      the explicit or implicit nature of the memory task alone is important for the
      distinction of MTL or BG systems. Nevertheless, patients with BG dysfunction -
      such as patients with Parkinson's disease (PD) or Huntington's disease (HD) - are
      considered to be impaired at implicit learning. However, a more recent study
      demonstrated that one implicit learning task, probabilistic classification
      learning (examples include the weather prediction (WPT) and Mr. Potato Head
      tasks) is only impaired in PD when it involves learning with corrective feedback
      (FB) but not when it involves learning in a paired associate (PA) manner, without
      feedback. Therefore, it has been argued that the presence of feedback rather than
      the implicit nature of these tasks determines whether or not the BG are
      recruited. As patients with HD as well as those with PD, have also been shown to
      be impaired on the standard FB based version of probabilistic classification
      learning, the question remains as to whether or not there is a similar selective
      deficit in FB but not PA based probabilistic classification learning in HD. 18
      patients with early HD and 18 healthy controls completed FB and PA versions of
      the WPT task. Relative to controls, HD patients were selectively impaired at WPT
      learning with feedback. These findings are consistent with previous evidence from
      studies of probabilistic classification learning in PD. Unlike PD, selective
      deficits in WPT learning in HD cannot be attributed to the effects of
      dopaminergic medication and must be directly related to BG dysfunction; for
      instance even in early HD, only 50% of the neurons in the medial head of caudate
      remain. We conclude that the striatum is important for WPT learning with
      feedback. Our findings are consistent with imaging evidence showing recruitment
      of the caudate during FB based WPT learning, while the MTL is associated with PA
      based learning.

PMID- 22659108
TI  - Age differences in the frontoparietal cognitive control network: implications for
      distractibility.
AB  - Current evidence suggests that older adults have reduced suppression of, and
      greater implicit memory for, distracting stimuli, due to age-related declines in
      frontal-based control mechanisms. In this study, we used fMRI to examine age
      differences in the neural underpinnings of attentional control and their
      relationship to differences in distractibility and subsequent memory for
      distraction. Older and younger adults were shown a rapid stream of words or
      nonwords superimposed on objects and performed a 1-back task on either the
      letters or the objects, while ignoring the other modality. Older adults were more
      distracted than younger adults by the overlapping words during the 1-back task,
      and they subsequently showed more priming for these words on an implicit memory
      task. A multivariate analysis of the imaging data revealed a set of regions,
      including the rostral PFC and inferior parietal cortex, that younger adults
      activated to a greater extent than older adults during the ignore-words
      condition, and activity in this set of regions was negatively correlated with
      priming for the distracting words. Functional connectivity analyses using right
      and left rostral PFC seeds revealed a network of putative control regions,
      including bilateral parietal cortex, connected to the frontal seeds at rest.
      Older adults showed reduced functional connectivity within this frontoparietal
      network, suggesting that their greater distractibility may be due to decreased
      activity and coherence within a cognitive control network that normally acts to
      reduce interference from distraction.

PMID- 22659111
TI  - Pre-orthographic character string processing and parietal cortex: a role for
      visual attention in reading?
AB  - The visual front-end of reading is most often associated with orthographic
      processing. The left ventral occipito-temporal cortex seems to be preferentially
      tuned for letter string and word processing. In contrast, little is known of the
      mechanisms responsible for pre-orthographic processing: the processing of
      character strings regardless of character type. While the superior parietal
      lobule has been shown to be involved in multiple letter processing, further data
      is necessary to extend these results to non-letter characters. The purpose of
      this study is to identify the neural correlates of pre-orthographic character
      string processing independently of character type. Fourteen skilled adult readers
      carried out multiple and single element visual categorization tasks with
      alphanumeric (AN) and non-alphanumeric (nAN) characters under fMRI. The role of
      parietal cortex in multiple element processing was further probed with a priori
      defined anatomical regions of interest (ROIs). Participants activated posterior
      parietal cortex more strongly for multiple than single element processing. ROI
      analyses showed that bilateral SPL/BA7 was more strongly activated for multiple
      than single element processing, regardless of character type. In contrast, no
      multiple element specific activity was found in inferior parietal lobules. These
      results suggests that parietal mechanisms are involved in pre-orthographic
      character string processing. We argue that in general, attentional mechanisms are
      involved in visual word recognition, as an early step of word visual analysis.

PMID- 22659112
TI  - Protective effect of ferulic acid and resveratrol against alloxan-induced
      diabetes in mice.
AB  - The present study was to investigate the effect of ferulic acid and resveratrol
      on alloxan-induced diabetic mice, through analysis of basic biochemical
      parameters, enzymic as well as non-enzymic activities, lipid peroxidation and
      immunohistochemical studies. Alloxan was administered as a single dose (75 mg/kg
      body weight) to induce diabetes in mice. A dose of ferulic acid (10 mg/kg body
      weight) and resveratrol (20 mg/kg body weight) were administrated orally, to the
      alloxan-induced diabetic mice. The levels of basic biochemical markers and lipid
      peroxidation were significantly (P<0.05) increased in alloxan-induced diabetic
      mice. The levels of antioxidants were significantly (P<0.05) decreased in liver,
      kidney and serum. Immunohistochemical studies in alloxan induced mice
      demonstrated a marked increase in the immunoreactivity of nuclear transcription
      factor (NF-kappaB). Treating the diabetic mice with doses of ferulic acid and
      resveratrol restored the changes in the above parameters analyzed. The present
      study, showed that ferulic acid and resveratrol exerted antioxidant as well as
      anti-diabetic effects, consequently alleviate liver, kidney and pancreas damage
      caused by alloxan-induced diabetes, probably through inhibition of the
      proinflammatory factor, NF-kappaB.

PMID- 22659113
TI  - Zonisamide up-regulated the mRNAs encoding astrocytic anti-oxidative and
      neurotrophic factors.
AB  - Zonisamide has been proven as an effective drug for the recovery of degenerating
      dopaminergic neurons in the animal models of Parkinson's disease. However,
      several lines of evidence have questioned the neuroprotective capacity of
      zonisamide in animal models of Parkinson's disease. Although it suppresses
      dopaminergic neurodegeneration in animal models, the cellular and molecular
      mechanisms underlying the effectiveness of zonisamide are not fully understood.
      The current study demonstrates the effects of zonisamide on astrocyte cultures
      and two 6-hydroxydopamine-induced models of Parkinson's disease. Using primary
      astrocyte cultures, we showed that zonisamide up-regulated the expression of mRNA
      encoding mesencephalic astrocyte-derived neurotrophic factor, vascular
      endothelial growth factor, proliferating cell nuclear antigen, metallothionein-2,
      copper/zinc superoxide dismutase, and manganese superoxide dismutase. Similar
      responses to zonisamide were found in substantia nigra where the rats were pre
      treated with 6-hydroxydopamine. Notably, pharmacological inhibition of 6
      hydroxydopamine-induced toxicity by zonisamide pre-treatment was also confirmed
      using rat mesencephalic organotypic slice cultures of substantia nigra. In
      addition to this, zonisamide post-treatment also attenuated the nigral tyrosine
      hydroxylase-positive neuronal loss induced by 6-hydroxydopamine. Taken together,
      these studies demonstrate that zonisamide protected dopamine neurons in two
      Parkinson's disease models through a novel mechanism, namely increasing the
      expression of some important astrocyte-mediated neurotrophic and anti-oxidative
      factors.

PMID- 22659115
TI  - Vasoconstrictor 5-HT receptors in the smooth muscle of the rat middle cerebral
      artery.
AB  - Serotonin (5-HT) can constrict cerebral arteries via activation of 5-HT(1B) and 5
      HT(2A) receptors. Our goal was to reveal the importance and relative contribution
      of the two 5-HT receptor subtypes to the serotonin-induced vasoconstriction in
      the rat middle cerebral artery. The vasoconstrictor effects of 5
      carboxamidotryptamine, sumatriptan and 5-HT were measured without and with pre
      treatment with SB 216641 (5-HT(1B) antagonist), or ritanserin, (5-HT(2A)
      antagonist), in endothelium-denuded arteries, in vitro. All agonists caused
      vasoconstrictions. The order of potency (EC(50)) of the compounds was: 5
      carboxamidotryptamine (14+/-3 nM)>5-HT (270+/-30 nM)>sumatriptan (5.8+/-1.9 MUM).
      The concentration-response curve of 5-carboxamidotryptamine resembled the sum of
      two sigmoid curves (EC(50) 14+/-3 nM and 15+/-7 MUM), and SB 216641 and
      ritanserin antagonized its low and high concentration components, respectively.
      Vasoconstrictions evoked by 5-HT at low and high concentrations were also fully
      antagonized by SB 216641 and ritanserin, respectively. Sumatriptan constricted
      the middle cerebral artery exclusively via 5-HT(1B) receptors. The efficacy of 5
      carboxamidotryptamine and sumatriptan was low in comparison to the maximum
      contractile force elicited by 120 mmol/l KCl, reaching only 18-23% for 5-HT(1B)
      and 14% for 5-HT(2A) receptor activation. In conclusion, 5-HT produced small
      vasoconstrictions in the rat middle cerebral artery that were mediated by 5
      HT(1B) receptors with high potency and by 5-HT(2A) receptors with low potency.
      Thus, 5-HT may have a minor physiological role in blood flow regulation via 5
      HT(1B) receptor activation while 5-HT(2A) receptors seem to have a
      pathophysiological role in this vessel.

PMID- 22659114
TI  - YC-1, a potent antithrombotic agent, induces lipolysis through the PKA pathway in
      rat visceral fat cells.
AB  - This study investigated the effects of 3-(5'-hydroxymethyl-2'-furyl)-1
      benzylindazole (YC-1), a soluble guanylyl cyclase (sGC) activator and potential
      antithrombotic agent, on lipolysis in isolated visceral fat cells of the rat.
      Visceral fat cells were isolated from epididymal fat pads of rats and treated
      with YC-1 at different doses and times. Glycerol release, and intracellular cAMP
      and cGMP levels were analyzed by specific kits. Moreover, several inhibitors or
      drugs were used to examine the signal transduction pathways of YC-1-induced
      lipolysis in adipocytes. Herein we report that YC-1 stimulated glycerol release
      in dose- and time-dependent manners. Intracellular cAMP and cGMP levels of
      adipocytes both increased in time-dependent manners, but elevation of the cGMP
      level was faster and higher than that of the cAMP level after YC-1 treatment. An
      sGC inhibitor (ODQ) inhibited YC-1-induced glycerol release, indicating the
      involvement of sGC in YC-1-induced lipolysis. Administration of insulin, an
      activator of type-3B phosphodiesterase (PDE-3B), attenuated YC-1-induced
      lipolysis, indicating that elevation of the cAMP level is an important step in
      the lipolytic effect of YC-1. In addition, YC-1-induced lipolysis was inhibited
      by a protein kinase A (PKA) inhibitor (KT5720) but not by a PKG inhibitor
      (KT5823), indicating that YC-1-induced lipolysis occurs through a PKA-dependent
      pathway. A Western blot analysis showed that extracellular signal-regulated
      kinase was not phosphorylated by YC-1 treatment. In conclusion, our results
      suggest that YC-1 might stimulate lipolysis via activation of sGC/cGMP and then
      activation of the cAMP/PKA signaling cascade in isolated rat visceral adipocytes.

PMID- 22659116
TI  - Inhibition of ectonucleotidase with ARL67156 prevents the development of calcific
      aortic valve disease in warfarin-treated rats.
AB  - Calcific aortic valve disease is the most common heart valve disorder. So far,
      there is no medical treatment for calcific aortic valve disease. The expression
      of ectonucleotidases, which metabolize nucleotides into phosphate products, may
      influence the calcification of the aortic valve. In this study, we investigated
      if the administration of an ectonucleotidase inhibitor, ARL67156 (6-N,N-Diethyl-D
      beta,gamma-dibromomethyleneATP trisodium salt), may prevent the calcification of
      the aortic valve in the warfarin-induced mineralization rat model. Male Wistar
      rats were treated with warfarin or warfarin+ARL67156 for 28 days. All rats had
      comprehensive Doppler-echocardiographic studies at 28 day. A gene profiling of
      ectonucleotidases expressed in aortas of rats was documented by quantitative real
      time PCR. The amount of calcium was determined by quantitative method and von
      Kossa staining. Ex vivo cultures of rat aortas were also used to further assess
      the effect of ARL67156 on the calcifying process and Akt signaling.
      Mineralization of the aorta/aortic valve was documented in warfarin-treated rats
      and was accompanied by the development of aortic stenosis. These changes were
      paralleled by an increased of ectonucleotide pyrophosphatase/phosphodiesterase-1
      (ENPP1). Administration of the ectonucleotidase inhibitor, ARL67156 prevented the
      development of aortic stenosis by lowering the level of apoptosis and
      mineralization of the aortic valve/aorta. In addition, ARL67156 normalized the
      level of pAkt, an important kinase involved in the survival pathway. Inhibition
      of ectonucleotidase activity prevented the development of calcific aortic valve
      disease in a rat model. On that account, ectonucleotidase may represent a novel
      target in the treatment of calcific aortic valve disease.

PMID- 22659117
TI  - Radical-induced DNA damage by cytotoxic square-planar copper(II) complexes
      incorporating o-phthalate and 1,10-phenanthroline or 2,2'-dipyridyl.
AB  - DNA-targeting copper(II) reagents have emerged as suitable drug candidates owing
      to the clinical success of the copper-activated, natural chemotherapeutic drug
      bleomycin. This agent and the synthetic chemical nuclease copper(II) bis-1,10
      phenanthroline represent important templates for inorganic drug design owing to
      their ability to initiate free radical DNA scission. Herein, we report the
      synthesis and biological properties of 1:1:1 square-planar copper(II) complexes
      incorporating the dicarboxylate o-phthalate and 1,10-phenanthroline (1) or 2,2'
      dipyridyl (2) ligands. Their broad-spectrum chemotherapeutic potential has been
      assessed at 24- and 96-h intervals, along with that of the clinical agent
      cisplatin, using breast (MCF-7), prostate (DU145), colon (HT29), and
      intrinsically cisplatin-resistant ovarian (SK-OV-3) human cancer cells. 1
      represents a potent cytotoxic agent with IC(50) values ranging from 5.6 to 3.4MUM
      across all cell lines, including SK-OV-3. The production of endogenous reactive
      oxygen species within SK-OV-3 cancer cells was monitored using the fluorophore
      2',7'-dichlorodihydrofluorescin diacetate, and results indicate a concentration
      dependent propensity toward ROS generation by 1 and 2 that mirrors their
      antitumoral behavior. DNA interaction studies, using fluorescence and viscosity
      measurements, were conducted in tandem with the DNA-targeting drugs actinomycin D
      and pentamidine, using calf thymus DNA, poly[d(A-T)(2)], and poly[d(G-C)(2)],
      with intercalation of 1 and 2 at the minor groove appearing to be the likely
      interaction mode. DNA cleavage reactions using superhelical plasmid DNA, in the
      presence of exogenous reductant, l-ascorbic acid, revealed excellent agreement
      between double-stranded DNA scission capability and antitumoral IC(50)
      concentration. The presence of double-strand DNA breaks (DSBs) was confirmed
      within SK-OV-3 cancer cells using immunodetection of gamma-H2AX foci by confocal
      microscopy and flow cytometry, with complex 1 quantitatively producing superior
      numbers of DSBs compared with complex 2. Superoxide dismutase and catalase
      mimetic activity assays were conducted, and these activities are related to the
      ability of both complexes to cleave DNA through free radical generation.

PMID- 22659118
TI  - Increased RLS prevalence in children and adolescents with migraine: a case
      control study.
AB  - BACKGROUND: Previous studies have reported an increased frequency of restless
      legs syndrome (RLS) in adult migraine patients. Until now, the frequency of RLS
      in pediatric patients has not been investigated. We set out to assess the
      frequency of RLS in children and adolescents with migraine compared to headache
      free controls. METHODS: We investigated 111 consecutive patients with a sole
      diagnosis of migraine with or without aura presenting to the Headache Unit at the
      Department of Child and Adolescent Psychiatry and 73 headache-free controls for
      the presence of RLS using a semistructured interview. In addition, we assessed
      the level of daytime sleepiness by means of the Epworth sleepiness scale (ESS). A
      second group of headache-free controls was screened for the presence of RLS using
      an online questionnaire. RESULTS: The frequency of RLS in migraine patients was
      significantly higher than in controls (22% vs. 5% (p < 0.001) and 8% (p <
      0.001)). DISCUSSION: This is the first study suggesting an association between
      RLS and migraine in the pediatric population. Future studies are needed to
      determine the extent of sleep disruption in children and adolescents with
      migraine and comorbid RLS.

PMID- 22659119
TI  - The structural basis for the narrow substrate specificity of an acetyl esterase
      from Thermotoga maritima.
AB  - Acetyl esterases from carbohydrate esterase family 7 exhibit unusual substrate
      specificity. These proteins catalyze the cleavage of disparate acetate esters
      with high efficiency, but are unreactive to larger acyl groups. The structural
      basis for this distinct selectivity profile is unknown. Here, we investigate a
      thermostable acetyl esterase (TM0077) from Thermotoga maritima using evolutionary
      relationships, structural information, fluorescent kinetic measurements, and site
      directed mutagenesis. We measured the kinetic and structural determinants for
      this specificity using a diverse series of small molecule enzyme substrates,
      including novel fluorogenic esters. These experiments identified two hydrophobic
      plasticity residues (Pro228, and Ile276) surrounding the nucleophilic serine that
      impart this specificity of TM0077 for small, straight-chain esters. Substitution
      of these residues with alanine imparts broader specificity to TM0077 for the
      hydrolysis of longer and bulkier esters. Our results suggest the specificity of
      acetyl esterases have been finely tuned by evolution to catalyze the removal of
      acetate groups from diverse substrates, but can be modified by focused amino acid
      substitutions to yield enzymes capable of cleaving larger ester functionalities.

PMID- 22659120
TI  - Laparoscopic treatment of a phytobezoar in the duodenal diverticulum - Report of
      a case.
AB  - INTRODUCTION: Primer small intestine bezoar is seen rarely. It frequently arises
      from underlying small intestine pathologies (diverticle, tumor, stricture etc.).
      We report a very rare case of disopyrobezoar in the duodenal diverticulum, a kind
      of phytobezoar caused by persimmons, which was treated laparoscopically.
      PRESENTATION OF CASE: The 47-year-old patient applied to polyclinic with
      complaints of epigastric tenderness, occasional distension, and acid
      regurgitation. In endoscopical examination, impacted bezoar was determined in the
      diverticulum in the duodenum. Because it is too hard, it was unable to remove
      endoscopically. On the abdominal tomography, a smooth-bounded non-homogeneous
      mass including gas and soft tissue areas in the 2nd portion of the duodenum was
      detected. A barium meal confirmed the presence of a 5cm diameter diverticulum on
      the lateral wall of the second portion of the duodenum. It also showed an
      intraluminalfilling defect as well as the mottled appearance of the bezoar.
      Learned from history of the patient, that the patient consumed over persimmon in
      childhood. DISCUSSION: Generally, duodenal diverticles are asymptomatic. Surgical
      treatment is rarely necessary because of complications such as bleeding,
      perforation, abdominal pain, bezoar formation. As well as using methods such as
      gastric lavage, enzymatic dissolution, endoscopical fragmentation in the
      treatment of phytobezoar, their chances of success are low because its structure
      is rigid. Usually, surgical intervention is required. CONCLUSION: For the
      treatments of bezoar cases located in the small intestine, laparoscopic surgical
      method is a safe and feasible method in selected cases.

PMID- 22659121
TI  - Intestinal melanoma: A broad spectrum of clinical presentation.
AB  - INTRODUCTION: Small intestine melanomas are rare and the most of them are
      metastases from primary cutaneous neoplasms. PRESENTATION OF CASE: Below, we
      report two cases of small intestine metastatic melanoma with very different
      clinical presentation. DISCUSSION: Still now, primary versus metastatic origin is
      often unclear. Small bowel melanoma is often asymptomatic. However, clinical
      picture can be various; it may occurs with non specific symptoms and signs of
      gastro-intetstinal involvement, like chronic abdominal pain, occult or gross
      bleeding and weight loss, or with an emergency picture due to intestinal
      intussusception, obstruction or, rarely, perforation. CONCLUSION: Small bowel
      melanoma is rare and the diagnosis done late. Imaging techniques are recommended
      in order to obtain early diagnosis of gastrointestinal metastases.

PMID- 22659122
TI  - Modification of the umu-assay (ISO 13829) accounting for cytotoxicity in
      genotoxicity assessment: a preliminary study.
AB  - In this study, the umu-assay (ISO 13829) was modified by addition of the
      resazurin-reduction assay to assess the cytotoxic potential of toxins. The aim
      was to develop a test system that was capable of examining both genotoxicity and
      cytotoxicity on the basis of the metabolic health of the cells so as to provide a
      better assessment of the negative influence of toxic effects on the evaluation of
      genotoxicity. The test was established and validated with mitomycin C (MMC), 1,3
      dinitropyrene (1,3-DNP), 4-nitroquinoline-1-oxide (4-NQO) and chloramphenicol
      (CHL) as toxins with known responses in the umu-assay. The results indicate that
      the modified umu-assay was able to reveal genotoxic responses towards MMC, 1,3
      DNP and 4-NQO up to 1MUg/ml. Further, the assay was able to determine the
      cytotoxicity of CHL, MMC and 4-NQO. Hence, the modified umu-assay was proven to
      be a sensitive test for determining the cytotoxicity and genotoxicity of toxins,
      with results that were comparable with literature data. Moreover, the modified
      umu-assay showed that cytotoxic concentrations that cause >50% inhibition of
      dehydrogenase activity (DHA) can result in unreliable computation of
      genotoxicity.

PMID- 22659123
TI  - Risks and untoward toxicities of antibody-based immunoconjugates.
AB  - Antibody-based immunoconjugates are specifically targeted monoclonal antibodies
      that deliver a cytotoxic payload to their target. The cytotoxic agents can be
      highly potent drugs, radionuclides or toxins. Such molecules, referred to as
      antibody-drug conjugates, radioimmunoconjugates and immunotoxins, respectively,
      represent a promising approach for enhancing the efficacy of unconjugated (naked)
      antibodies for improved therapeutic results. Though tremendous progress has been
      achieved over the last few decades, the safety of these molecules still remains a
      matter of concern and a careful design is required for achieving a relatively
      safe toxicity profile along with therapeutic effectiveness. This review focuses
      on the toxicities arising from the use of these potent agents.

PMID- 22659124
TI  - Development of a spray-drying method for the formulation of respirable
      microparticles containing ofloxacin-palladium complex.
AB  - The purpose of this study was to produce low-releasing spray-dried polymeric
      microparticles (MP) useful to target alveolar macrophages in tuberculosis (TB)
      inhalation therapy. Ofloxacin (Ofx) was encapsulated as ofloxacin-palladium (Ofx
      Pd) complex into poly DL-lactide (PLA) MP by spray-drying. Ofx-Pd was prepared
      according to a method previously reported. A D-optimal design was employed to
      optimize drug content (DC), aerodynamic diameter (d(ae)) and span. d(ae) was
      calculated coupling tap-density to particle size analysis. The MP were
      characterized by SEM, UV spectrophotometry, and DSC. In vitro drug release was
      performed in comparison to Ofx loaded PLA MP. The Ofx-Pd complex formed
      spontaneously with a 1:1 stoichiometry. Inlet temperature, drug loading and
      polymer concentration resulted the most influential. Optimal MP had span of 0.9,
      a round shape, d(ae) of 2.5 MUm, and DC of 30% (w/w). DSC and SEM analyses
      correlated with particle size. The optimized MP formulation showed a very low
      release at pH 7.4 compared to spray-dried Ofx loaded MP, the release increased
      slightly at lower pHs. Potentially inhalable MP were obtained by an optimized
      spray-drying process. The very low initial drug release at physiologic pH could
      be useful to target alveolar macrophages and to avoid systemic exposure.

PMID- 22659125
TI  - Development and evaluation of taste-masked drug for paediatric medicines -
      application to acetaminophen.
AB  - The aim of this work was to produce and characterize taste-masked powders of a
      model drug (acetaminophen) prepared using potentially tolerable and safe
      excipients for paediatric use, i.e. sodium caseinate and lecithin. The powders
      were produced by spray-drying aqueous dispersions. The characteristics of taste
      masked drug particles were determined by scanning electron microscopy,
      differential scanning calorimetry and X-ray photoelectron spectroscopy to analyse
      the surface composition of particles. Taste assessment was approached by an
      indirect method through drug release studies. We developed a method with a
      syringe pump using small volumes of aqueous medium and low flow rates, to mimic
      the behaviour in the mouth. This method was compared to the electronic tongue
      analysis. SEM, DSC and XPS analysis indicated differences in surface composition
      of spray-dried particles according to the caseinate/lecithin ratio and to relate
      it with taste-masking. The "coating" consisting of caseinate and lecithin had a
      significant role in decreasing the release of drug during the first 2 min and so
      in taste-masking. Higher content in lecithin results in higher taste-masking
      efficiency. The association of sodium caseinate and lecithin seems to be
      promising to mask the bitterness of acetaminophen. A good agreement between
      release study and electronic tongue analysis was established.

PMID- 22659126
TI  - Comparison of in vitro-in vivo release of Risperdal((r)) Consta((r))
      microspheres.
AB  - The objective was to investigate the relationship between in vitro and in vivo
      release of commercial Risperdal((r)) Consta((r)) microspheres. A modified USP
      apparatus 4 method was used for accelerated and real-time in vitro release
      testing. The in vivo plasma profile (clinical data) reported for the product was
      deconvoluted for comparison with the in vitro release profiles. The in vivo
      profile differed from the real-time in vitro profile and was faster initially and
      then slower after approximately 30 days. This effect is considered to be due to
      differences in the in vivo conditions such as small interstitial volume, low pH
      and immune response. Accelerated in vitro release profiles obtained at
      temperatures (50 degrees C and 54.5 degrees C) above the microsphere glass
      transition temperature (Tg~48 degrees C) overlapped with the in vivo profile
      after time scaling. A linear in vitro-in vivo relationship was observed with
      correlation coefficients of 0.97 and 0.99 at 50 degrees C and 54.5 degrees C,
      respectively. The accelerated test performed below the Tg had a similar release
      profile to that of the real-time in vitro test. The accelerated tests performed
      above the Tg of the microspheres showed the potential to be used for in vivo
      performance prediction as well as for quality control purposes.

PMID- 22659127
TI  - Idebenone-loaded solid lipid nanoparticles for drug delivery to the skin: in
      vitro evaluation.
AB  - Idebenone (IDE), a synthetic derivative of ubiquinone, shows a potent antioxidant
      activity that could be beneficial in the treatment of skin oxidative damages. In
      this work, the feasibility of targeting IDE into the upper layers of the skin by
      topical application of IDE-loaded solid lipid nanoparticles (SLN) was evaluated.
      SLN loading different amounts of IDE were prepared by the phase inversion
      temperature method using cetyl palmitate as solid lipid and three different non
      ionic surfactants: ceteth-20, isoceteth-20 and oleth-20. All IDE loaded SLN
      showed a mean particle size in the range of 30-49 nm and a single peak in size
      distribution. In vitro permeation/penetration experiments were performed on pig
      skin using Franz-type diffusion cells. IDE penetration into the different skin
      layers depended on the type of SLN used while no IDE permeation occurred from all
      the SLN under investigation. The highest IDE content was found in the epidermis
      when SLN contained ceteth-20 or isoceteth-20 as surfactant while IDE distribution
      into the upper skin layers depended on the amount of IDE loaded when oleth-20 was
      used as surfactant. These results suggest that the SLN tested could be an
      interesting carrier for IDE targeting to the upper skin layers.

PMID- 22659128
TI  - Nasal stimulation by water down-regulates cough in anesthetized rabbits.
AB  - The 'cough center' can be tuned by various afferent inputs, suggesting possible
      interactions at a central level of neural pathways originating from distant
      anatomical sites. The present study was designed to determine whether brief
      mechanical stimulation of the trachea can trigger cough during apnea elicited by
      nasal instillation of water. Twelve anesthetized, tracheotomized rabbits were
      studied. Mechanical stimulation of the trachea was performed under 3 conditions:
      baseline control, after instillation of saline into the nose and during apnea
      following instillation of water. The baseline breathing pattern did not differ
      between the 3 conditions. In a series of 171 stimulations, expiration reflex
      occurred in 81% of stimulations during apnea with a significantly (p<0.0001)
      lower peak expiratory flow than at baseline or during saline instillation. The
      incidence of responses comprising a cough reflex was also lower during water
      instillation than at either baseline or with saline (p<0.0001). These results
      indicate that stimulation of nasal afferents with distilled water likely down
      regulates cough.

PMID- 22659129
TI  - High hepcidin level accounts for the nigral iron accumulation in acute peripheral
      iron intoxication rats.
AB  - Hepcidin is considered to be a circulatory hormone and a major mechanism
      regulating iron homeostasis. Our previous publication revealed that acute iron
      intoxication induced iron deposit and dopaminergic neuron degeneration in the
      substantia nigra (SN) of a rat model. However, whether and how hepcidin functions
      in this nigral iron accumulation has not been elucidated. In the present study,
      we observed a decreased of FPN1 protein level in the SN triggered by peripheral
      iron overload within 4 h, which correlated with a high hepcidin level. To further
      investigate the role of intracellular hepcidin under iron overload circumstances,
      we assessed the expression of hepcidin mRNA and FPN1 protein in vitro. We
      observed that hepcidin mRNA level was up-regulated and FPN1 protein level was
      down-regulated in MES23.5 dopaminergic cells in a period of 4h incubation with
      iron. Both in pCMV-XL4-hepcidin transfected and hepcidin-treated cells, decreased
      FPN1 protein levels were observed. Our data provide direct evidence that the role
      for intracellular hepcidin generated in the SN is particularly relevant to
      restrict iron release by down-regulation FPN1 expression in this region, thus an
      important contributor to the abnormal iron deposit occurred at an early stage in
      conditions of peripheral iron intoxication.

PMID- 22659130
TI  - De-ubiquitinating proteases USP2a and USP2c cause apoptosis by stabilising RIP1.
AB  - Dynamic ubiquitination impacts on the degradation of proteins by the proteasome
      as well as on their effects as signalling factors. Of the many cellular responses
      that are regulated by changes in ubiquitination, apoptosis has garnered special
      attention. We have found that USP2a and USP2c, two isoforms of the ubiquitin
      specific protease USP2, cause cell death upon ectopic expression. We show that
      both USP2 isoforms can control the ubiquitination status of many proteins but
      from a panel of potential targets only the protein level of RIP1 was increased by
      these enzymes. This effect is responsible for the activity of USP2a and USP2c to
      cause cell death. Both enzymes likewise de-ubiquitinate TRAF2, a ubiquitin-ligase
      in the TNFR1 complex. Whilst this and the similar sub-cellular localisations of
      both enzyme isoforms indicate a substantial overlap of activities, inactivation
      by RNAi revealed that only the knock-down of USP2c resulted in apoptosis, whilst
      targeting USP2a did not have any consequence on the cells' survival.
      Consequently, we focussed our studies on USP2a and found that TRAF2 inhibits
      USP2a's effect on K48- but not on K63-linked ubiquitin chains. Hence, the ratio
      between USP2a and TRAF2 protein levels determines the cells' sensitivity to cell
      death.

PMID- 22659131
TI  - C3G transgenic mouse models with specific expression in platelets reveal a new
      role for C3G in platelet clotting through its GEF activity.
AB  - We have generated mouse transgenic lineages for C3G (tgC3G) and C3GDeltaCat
      (tgC3GDeltaCat, C3G mutant lacking the GEF domain), where the transgenes are
      expressed under the control of the megakaryocyte and platelet specific PF4
      (platelet factor 4) gene promoter. Transgenic platelet activity has been analyzed
      through in vivo and in vitro approaches, including bleeding time, aggregation
      assays and flow cytometry. Both transgenes are expressed (RNA and protein) in
      purified platelets and megakaryocytes and do not modify the number of platelets
      in peripheral blood. Transgenic C3G animals showed bleeding times significantly
      shorter than control animals, while tgC3GDeltaCat mice presented a remarkable
      bleeding diathesis as compared to their control siblings. Accordingly, platelets
      from tgC3G mice showed stronger activation in response to platelet agonists such
      as thrombin, PMA, ADP or collagen than control platelets, while those from
      tgC3GDeltaCat animals had a lower response. In addition, we present data
      indicating that C3G is a mediator in the PKC pathway leading to Rap1 activation.
      Remarkably, a significant percentage of tgC3G mice presented a higher level of
      neutrophils than their control siblings. These results indicate that C3G plays an
      important role in platelet clotting through a mechanism involving its GEF
      activity and suggest that it might be also involved in neutrophil development.

PMID- 22659132
TI  - Global bang for the buck: cutting black carbon and methane benefits both health
      and climate.

PMID- 22659133
TI  - The Werner syndrome gene product (WRN): a repressor of hypoxia-inducible factor-1
      activity.
AB  - Werner syndrome (WS) is a rare autosomal disease characterized by the premature
      onset of several age-associated pathologies. The protein defective in WS patients
      (WRN) is a helicase/exonuclease involved in DNA repair, replication,
      transcription and telomere maintenance. Hypoxia-inducible factor-1 (HIF-1) is a
      decisive element for the transcriptional regulation of genes essential for
      adaptation to low oxygen conditions. HIF-1 is also implicated in the molecular
      mechanisms of ageing. Here, we show that the cellular depletion of WRN protein
      (by siRNA targeting) leads to increased HIF-1 complex stabilization and
      activation. HIF-1 activation in the absence of WRN involves the generation of
      mitochondrial reactive oxygen species (mtROS) since SkQ1, a mitochondrial
      targeted antioxidant, and stigmatellin, an inhibitor of mitochondrial complex
      III, blocked increased HIF-1 levels. Ascorbate, an essential co-factor involved
      in HIF-1 stability, was decreased in WRN-depleted cells. Interestingly,
      expression levels of GLUT1, a known dehydroascorbic acid transporter, were also
      decreased in WRN-depleted cells. Ascorbate supplementation of WRN-depleted cells
      led to a dose-dependent inhibition of HIF-1 activation. These results indicate
      that WRN protein regulates HIF-1 activation by affecting mitochondrial ROS
      production and intracellular ascorbate levels. This work provides a novel
      mechanistic link between HIF-1 activity and different age-associated pathologies.

PMID- 22659135
TI  - Intricacies of hedgehog signaling pathways: a perspective in tumorigenesis.
AB  - The hedgehog (HH) signaling pathway is a crucial negotiator of developmental
      proceedings in the embryo governing a diverse array of processes including cell
      proliferation, differentiation, and tissue patterning. The overall activity of
      the pathway is significantly curtailed after embryogenesis as well as in adults,
      yet it retains many of its functional capacities. However, aberration in HH
      signaling mediates the initiation, proliferation and continued sustenance of
      malignancy in different tissues to varying degrees through different mechanisms.
      In this review, we provide an overview of the role of constitutively active
      aberrant HH signaling pathway in different types of human cancer and the
      underlying molecular and genetic mechanisms that drive tumorigenesis in that
      particular tissue. An insight into the various modes of anomalous HH signaling in
      different organs will provide a comprehensive knowledge of the pathway in these
      tissues and open a window for individually tailored, tissue-specific therapeutic
      interventions. The synergistic cross talking of HH pathway with many other
      regulatory molecules and developmentally inclined signaling pathways may offer
      many avenues for pharmacological advances. Understanding the molecular basis of
      abnormal HH signaling in cancer will provide an opportunity to inhibit the
      deregulated pathway in many aggressive and therapeutically challenging cancers
      where promising options are not available.

PMID- 22659134
TI  - Spleen tyrosine kinase mediates high glucose-induced transforming growth factor
      beta1 up-regulation in proximal tubular epithelial cells.
AB  - The role of spleen tyrosine kinase (Syk) in high glucose-induced intracellular
      signal transduction has yet to be elucidated. We investigated whether Syk is
      implicated in high glucose-induced transforming growth factor-beta1 (TGF-beta1)
      up-regulation in cultured human proximal tubular epithelial cells (HK-2 cell).
      High glucose increased TGF-beta1 gene expression through Syk, extracellular
      signal-regulated kinase (ERK), AP-1 and NF-kappaB. High glucose-induced AP-1 DNA
      binding activity was decreased by Syk inhibitors and U0126 (an ERK inhibitor).
      Syk inhibitors suppressed high glucose-induced ERK activation, whereas U0126 had
      no effect on Syk activation. High glucose-induced NF-kappaB DNA binding activity
      was also decreased by Syk inhibitors. High glucose increased nuclear
      translocation of p65 without serine phosphorylation of IkappaBalpha and without
      degradation of IkappaBalpha, but with an increase in tyrosine phosphorylation of
      IkappaBalpha that may account for the activation of NF-kappaB. Both Syk
      inhibitors and Syk-siRNA attenuated high glucose-induced IkappaBalpha tyrosine
      phosphorylation and p65 nuclear translocation. Depletion of p21-activated kinase
      2 (Pak2) by transfection of Pak2-siRNA abolished high glucose-induced Syk
      activation. In summary, high glucose-induced TGF-beta1 gene transcription
      occurred through Pak2, Syk and subsequent ERK/AP-1 and NF-kappaB pathways. This
      suggests that Syk might be implicated in the diabetic kidney disease.

PMID- 22659136
TI  - Urinary total arsenic and 8-hydroxydeoxyguanosine are associated with renal cell
      carcinoma in an area without obvious arsenic exposure.
AB  - 8-Hydroxydeoxyguanosine (8-OHdG) is one of the most reliable and abundant markers
      of DNA damage. The study was designed to explore the relationship between urinary
      8-OHdG and renal cell carcinoma (RCC) and to investigate whether individuals with
      a high level of 8-OHdG would have a modified odds ratio (OR) of arsenic-related
      RCC. This case-control study was conducted with 132 RCC patients and 245 age- and
      sex-matched controls from a hospital-based pool between November 2006 and May
      2009. Pathological verification of RCC was completed by image-guided biopsy or
      surgical resection of renal tumors. Urinary 8-OHdG levels were determined using
      liquid chromatography with tandem mass spectrometry (LC-MS/MS). Concentrations of
      urinary arsenic species, including inorganic arsenic, monomethylarsonic acid
      (MMA) and dimethylarsinic acid (DMA), were determined by a high performance
      liquid chromatography-linked hydride generator and atomic absorption
      spectrometry. Level of urinary 8-OHdG was significantly associated with the OR of
      RCC in a dose-response relationship after multivariate adjustment. Urinary 8-OHdG
      was significantly related to urinary total arsenic. The greatest OR (3.50) was
      seen in the individuals with high urinary 8-OHdG and high urinary total arsenic.
      A trend test indicated that the OR of RCC was increased with one of these factors
      and was further increased with both (p=0.002). In conclusion, higher urinary 8
      OHdG was a strong predictor of the RCC. High levels of 8-OHdG combined with
      urinary total arsenic might be indicative of arsenic-induced RCC.

PMID- 22659137
TI  - Signaling pathways in chronic myeloid leukemia and leukemic stem cell
      maintenance: key role of stromal microenvironment.
AB  - Chronic myeloid leukemia (CML) is caused by the malignant transformation of
      hematopoietic stem cells in leukemic stem cells. From the introduction of the
      anti-cancer drug imatinib, the therapy of CML has been positively transformed.
      However, following treatment most patients display a residual CML disease
      attributed to the presence of quiescent leukemic stem cells intrinsically
      resistant to imatinib. Considering that the later cancer cells lose their
      chemoresistance in vitro, it appears that the stromal microenvironment plays a
      crucial role in CML-affected cell chemoresistance. In the present review, we
      summarize and discuss the recent findings on signaling pathways through which
      stromal cells sustain CML leukemogenesis, as well as leukemic stem cell
      maintenance and chemoresistance.

PMID- 22659138
TI  - Arf6 guanine-nucleotide exchange factor, cytohesin-2, interacts with actinin-1 to
      regulate neurite extension.
AB  - Proper regulation of morphological changes in neuronal cells is essential for
      their differentiation. Complex signaling mechanisms mediate a variety of
      morphological changes such as formation of neurites. It is well established that
      a number of small GTPases control neurite behavior before the connection with the
      target tissue. However, their regulatory mechanisms remain to be fully
      understood. Here, we show that the Arf6 guanine-nucleotide exchange factor (GEF),
      cytohesin-2 (CYTH2), interacts with the cytoskeletal protein actinin-1 (ACTN1)
      and regulates neurite extension in N1E-115 cells used as the model. Knockdown of
      ACTN1, as well as that of CYTH2, in cells inhibits cellular Arf6 activity and
      neurite extension. The C-terminal polybasic region of CYTH2 participates in
      interacting directly with the EFh2 domain of ACTN1. Expression of CYTH2 mutant
      deficient of the EFh2 domain in cells also inhibits Arf6 activation and neurite
      extension. Furthermore, FRET analysis detects that the respective interactive
      region peptides, tagged with cell-permeable short peptides, greatly decrease Arf6
      activation at growth cones in a time-dependent manner. Collectively, the
      signaling through CYTH2 and ACTN1 properly regulates neurite extension in N1E-115
      cells, demonstrating the unexpected interaction of CYTH2 and ACTN1 in the
      regulation of cellular Arf6 activity involved in neurite extension.

PMID- 22659139
TI  - Regulation of Six1 expression by evolutionarily conserved enhancers in tetrapods.
AB  - The Six1 homeobox gene plays critical roles in vertebrate organogenesis. Mice
      deficient for Six1 show severe defects in organs such as skeletal muscle, kidney,
      thymus, sensory organs and ganglia derived from cranial placodes, and mutations
      in human SIX1 cause branchio-oto-renal syndrome, an autosomal dominant
      developmental disorder characterized by hearing loss and branchial defects. The
      present study was designed to identify enhancers responsible for the dynamic
      expression pattern of Six1 during mouse embryogenesis. The results showed
      distinct enhancer activities of seven conserved non-coding sequences (CNSs)
      retained in tetrapod Six1 loci. The activities were detected in all cranial
      placodes (excluding the lens placode), dorsal root ganglia, somites, nephrogenic
      cord, notochord and cranial mesoderm. The major Six1-expression domains during
      development were covered by the sum of activities of these enhancers, together
      with the previously identified enhancer for the pre-placodal region and foregut
      endoderm. Thus, the eight CNSs identified in a series of our study represent
      major evolutionarily conserved enhancers responsible for the expression of Six1
      in tetrapods. The results also confirmed that chick electroporation is a robust
      means to decipher regulatory information stored in vertebrate genomes. Mutational
      analysis of the most conserved placode-specific enhancer, Six1-21, indicated that
      the enhancer integrates a variety of inputs from Sox, Pax, Fox, Six, Wnt/Lef1 and
      basic helix-loop-helix proteins. Positive autoregulation of Six1 is achieved
      through the regulation of Six protein-binding sites. The identified Six1
      enhancers provide valuable tools to understand the mechanism of Six1 regulation
      and to manipulate gene expression in the developing embryo, particularly in the
      sensory organs.

PMID- 22659141
TI  - Nanoscale characterization of acid and thermally treated collagen fibrils.
AB  - Type I collagen is a major extracellular matrix component and its hierarchical
      structure plays an essential role in the regulation of cellular behavior. Here,
      we have analyzed the changes in the morphological, chemical, and mechanical
      properties of collagen fibrils induced by acidic and thermal treatments and the
      influence on the cellular response of MC3T3-E1 cells. Morphological changes
      induced by the disintegration of the fibrillar structure of collagen were
      observed using atomic force microscopy. The changes in the surface chemistry due
      to the disassembly of native collagen fibrils were observed using time-of-flight
      secondary ion mass spectroscopy (ToF-SIMS). ToF-SIMS spectra were very sensitive
      to changes in the molecular configuration of the collagen fibrils induced by
      acidic and thermal treatments due to the extreme surface specificity. In
      addition, ToF-SIMS showed clear and reproducible changes in the surface amino
      acid composition corresponding to the acidic and thermal treatments of collagen
      fibrils. Based on the quantitative map of surface elastic modulus measured by
      contact-resonance force microscopy, acid and thermally treated collagen showed a
      lower elastic modulus than native collagen fibrils. Compared with native collagen
      fibrils, reduced cell spreading and decreased viability of MC3T3-E1 cells were
      observed on both the acid and thermally treated collagen.

PMID- 22659140
TI  - Tbl3 regulates cell cycle length during zebrafish development.
AB  - The regulation of cell cycle rate is essential for the correct timing of
      proliferation and differentiation during development. Changes to cell cycle rate
      can have profound effects on the size, shape and cell types of a developing
      organ. We previously identified a zebrafish mutant ceylon (cey) that has a severe
      reduction in T cells and hematopoietic stem/progenitor cells (HSPCs). Here we
      find that the cey phenotype is due to absence of the gene transducin (beta)-like
      3 (tbl3). The tbl3 homolog in yeast regulates the cell cycle by maintaining rRNA
      levels and preventing p53-induced cell death. Zebrafish tbl3 is maternally
      expressed, but later in development its expression is restricted to specific
      tissues. Tissues expressing tbl3 are severely reduced in cey mutants, including
      HSPCs, the retina, exocrine pancreas, intestine, and jaw cartilage. Specification
      of these tissues is normal, suggesting the reduced size is due to a reduced
      number of differentiated cells. Tbl3 MO injection into either wild-type or p53-/-
      mutant embryos phenocopies cey, indicating that loss of tbl3 causes specific
      defects in cey. Progression of both hematopoietic and retinal development is
      delayed beginning at 3 day post fertilization due to a slowing of the cell cycle.
      In contrast to yeast, reduction of Tbl3 causes a slowing of the cell cycle
      without a corresponding increase in p53 induced cell death. These data suggest
      that tbl3 plays a tissue-specific role regulating cell cycle rate during
      development.

PMID- 22659142
TI  - Lipid bilayer condition abnormalities following Macrovipera lebetina obtusa snake
      envenomation.
AB  - Viper bites is an endemic public health problem in Armenia, even in the cities.
      Human envenomation is often characterized by clotting disorders,
      hypofibrinogenemia, and local tissue necrosis. In this original study, we assess
      some changes of cell membranes plastic properties (namely, its microviscosity,
      thickness, permeability) in a rat envenomation model using the biophysical
      approaches. We describe the interaction of Macrovipera lebetina obtusa (MLO)
      venom with giant unilamellar vesicles (GUVs) composed of the native phospholipid
      mixtures visualized through fluorescent microscopy. GUVs with a mean diameter of
      30 MUm have a minimum curvature and mimic cell membranes in this respect. The
      membrane fluorescence probe, ANS and pyrene, were used to assess the state of
      membrane and specifically mark the phospholipid domains. Independent of their
      lipid composition, GUVs were enlarged in size as venom-dependent lipid hydrolysis
      proceeded. Except of the visible morphological changes, ANS and pyrene also
      allows us to quantify the fluidity changes in the membrane by measuring of the
      fluorescence intensity. The presence of viper venom in GUVs media reveals a
      noticeable decreasing of membrane fluidity compare the control, while the binding
      of fluorophores with GUVs modified by venom lead to appearance of channel
      activity. These studies also emphasize the importance of a membrane surface
      curvature for its interaction with enzymatic components of venom.

PMID- 22659143
TI  - Terminal reduction reactions of nitrate and sulfate assimilation in Streptomyces
      coelicolor A3(2): identification of genes encoding nitrite and sulfite
      reductases.
AB  - The model actinobacterium Streptomyces coelicolor A3(2) uses nitrate and sulfate
      as nitrogen and sulfur sources, respectively. The final step prior to
      assimilation into amino acids is the 6-electron reduction of the nitrite and
      sulfite anions, catalyzed by siroheme-dependent nitrite (NirBD) and sulfite
      (SirA) reductases. There are two predicted nitrite/sulfite reductases annotated
      in the genome of S. coelicolor, but it is unclear which is responsible for
      nitrite and which for sulfite reduction. Here we demonstrate that a knock-out in
      the genes SCO2487 and SCO2488 encoding NirBD prevents use of nitrite as a
      nitrogen source, while a knock-out in SCO6102 encoding SirA prevents sulfate
      assimilation. Both mutations could be phenotypically complemented by
      supplementation of the growth medium with ammonium or casamino acids in the case
      of the nirBD mutants or sulfur-containing amino acids in the case of the sirA
      mutants. No functional redundancy between the genes was observed and we
      demonstrate that NirBD is exclusively required for assimilatory nitrite (it does
      not detoxify nitrite) and SirA exclusively for assimilatory sulfite reduction.

PMID- 22659144
TI  - Variability of the tandem repeat region of the Escherichia coli tolA gene.
AB  - An intragenic tandem repeat (TR) region has been previously reported in the tolA
      gene of Escherichia coli. In silico analysis of 123 E. coli tolA sequences from
      Genbank and PCR analysis of the tolA TR region from 111 additional E. coli
      strains revealed that this TR region is highly variable. Nine different TR sizes
      with 8 up to 16 repeat units were found in in silico analysis and 6 of these were
      also found by PCR analysis. The 13-unit TR emerged as the predominant type using
      both approaches (47.2% and 86.5%, respectively). Remarkably, TRs in pathogenic
      strains appeared to be more variable than those in non-pathogens. To demonstrate
      the occurrence of TR variation in a clonal population, a selection system for TR
      deletion events was constructed by inserting the 13-unit TR region of MG1655 in
      frame into a plasmid-borne chloramphenicol acetyltransferase (cat) gene. The
      resulting cat gene no longer conferred chloramphenicol resistance unless the
      insert size was reduced by TR contraction. Using this system, Cm-resistant
      revertants with a TR contraction were recovered at a frequency of 1.1 * 10(-7),
      and contraction was shown to be recA-dependent and enhanced in a DNA repair
      deficient mutS background.

PMID- 22659145
TI  - Resveratrol helps recovery from fatty liver and protects against hepatocellular
      carcinoma induced by hepatitis B virus X protein in a mouse model.
AB  - Resveratrol is a natural polyphenol that has beneficial effects across species
      and various disease models. Here, we investigate whether resveratrol is effective
      against hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) using
      HBV X protein (HBx) transgenic mice. We found that resveratrol (30 mg/kg/d) has a
      therapeutic effect on HBx-induced fatty liver and the early stages of liver
      damage. Resveratrol decreased intracellular reactive oxygen species and
      transiently stimulated hepatocyte proliferation. Interestingly, resveratrol
      inhibited LXRalpha and downregulated the expression of the lipogenic genes,
      Srebp1-c and PPARgamma. The decrease in Srebp1-c seems to further downregulate
      the expression of its target genes, Acc and Fas. In addition, resveratrol
      stimulated the activity of Ampk and SirT1. Thus, resveratrol has a pleiotropic
      effect on HBx transgenic mice in terms of the downregulation of lipogenesis, the
      promotion of transient liver regeneration, and the stimulation of antioxidant
      activity. Furthermore, at the later precancerous stages, resveratrol delayed HBx
      mediated hepatocarcinogenesis and reduced HCC incidence from 80% to 15%, a 5.3
      fold reduction. Resveratrol should be considered as a potential chemopreventive
      agent for HBV-associated HCC.

PMID- 22659146
TI  - Highly potent activation of Nrf2 by topical tricyclic bis(cyano enone):
      implications for protection against UV radiation during thiopurine therapy.
AB  - Chronic treatment with azathioprine, a highly effective anti-inflammatory and
      immunosuppressive agent, profoundly increases the risk for development of
      unusually aggressive cutaneous squamous cell carcinoma. Its ultimate metabolite,
      6-thioguanine (6-TG) nucleotide, is incorporated in DNA of skin cells, and upon
      exposure to UVA radiation, causes oxidative stress, followed by damage of DNA and
      associated proteins. The acetylenic tricyclic bis(cyano enone) TBE-31 is a strong
      inhibitor of inflammation and a potent inducer of the Keap1/Nrf2/ARE pathway,
      which orchestrates the expression of a large network of cytoprotective genes. We
      now report that long-term (five days per week for four weeks) topical daily
      applications of small (200 nmol) quantities of TBE-31 cause a robust systemic
      induction of the Keap1/Nrf2/ARE pathway and decreases the 6-TG incorporation in
      DNA of skin, blood, and liver of azathioprine-treated mice, indicating
      extraordinary bioavailability and efficacy. In addition, TBE-31, at nanomolar
      concentrations, protects cells with 6-TG in their genomic DNA against oxidative
      stress caused by UVA radiation through induction of the Keap1/Nrf2/ARE pathway.
      At the same 6-TG DNA levels, Keap1-knockout cells, in which the pathway is
      constitutively upregulated, are highly resistant to UVA radiation-induced
      oxidative stress. The protective effects of both the Keap1-knockout genotype and
      TBE-31 are completely lost in the absence of transcription factor Nrf2. Our
      findings suggest that compounds of this kind are excellent candidates for
      mechanism-based chemoprotective agents against conditions in which oxidative
      stress and inflammation underlie disease pathogenesis. Moreover, their potential
      skin patch incorporation for transdermal delivery is an exciting possibility.

PMID- 22659147
TI  - The inflow of 238Pu and (239+240)Pu from the Odra and Pomeranian rivers
      catchments area to the Baltic Sea.
AB  - The aim of the work was to estimate plutonium inflow from the Odra River
      catchments area to the Baltic Sea. The highest activities of (238)Pu and
      (239+240)Pu were observed in a winter and a spring season. The highest annual
      surface inflow of (239+240)Pu from the Odra River watershed was observed for a
      mountain tributary the Bobr (1230 Bq km(-2) year(-1)). The annual inflow of
      (238)Pu and (239+240)Pu to the Baltic Sea was estimated at 9.51 MBq and 45.86 MBq
      respectively and the highest plutonium surface runoff was observed for the Bobr
      drainage.

PMID- 22659148
TI  - Recent gamma background measurements at high mountain altitude.
AB  - Results from recent measurements of radiation gamma background at high mountain
      altitude, namely at Basic Environmental Observatory Moussala (42.11 N, 23.35 E,
      2925 m a.s.l.) are reported. The measurements are fulfilled with several devices,
      namely IGS-421 gamma probe and MDU Liulin. A comparative analysis with previous
      measurements performed with SBN-90 SAPHYMO NaI(Tl) gamma probe is carried out. A
      temperature effect during winter period of SAPHYMO probe is observed. In addition
      the measurements are compared with CaSO(4):Dy TLD. The obtained results are
      widely discussed. A numerical model for galactic cosmic ray contribution to the
      dose rate in air is presented. The model is based on a full Monte Carlo
      simulation of cosmic ray induced cascade in the atmosphere. The simulation is
      carried out with CORSIKA 6.52 code using FLUKA 2006b and QGSJET II hadron
      interaction models.

PMID- 22659149
TI  - Study of the potential of stratum corneum lipids and exogenous molecules
      interaction by fluorescence spectroscopy for the estimation of percutaneous
      penetration.
AB  - Considering that the skin barrier properties are closely linked to the ceramides
      composition and conformation within the SC, our work focused on developing a new
      evaluation criterion in complement of the Log Pow and MW: lipids retentive role
      within the SC. We developed an in vitro model to study exogenous molecules (Mol)
      and SC lipids interaction by fluorescence spectroscopy. As ceramides do not
      fluoresce, fluorescence probes that emit a fluorescence signal in contact with
      lipidic chains were selected for the study. A protocol was developed based on the
      exogenous molecule (cosmetic actives) affinity for the SC lipids. A fluorescence
      criterion (DeltaI) was calculated from our results and compared to ex vivo skin
      penetration measurements realized with a Franz cell device. Our results indicated
      that polarity seems to be very representative of the ceramide and exogenous
      molecule interaction for most of the molecules tested. However, the DeltaI
      calculated highlighted the particular interaction of some exogenous molecules
      with ceramides and their skin distribution. This particular behavior was not
      initially possible to estimate with the Log Pow and MW. This work aimed to
      develop a new alternative method to enhance the percutaneous penetration
      estimation of exogenous molecules for the risk analysis.

PMID- 22659150
TI  - The influence of plate design on the properties of pellets produced by extrusion
      and spheronization.
AB  - The aim of this work was to produce pellets using a standard formulation by means
      of extrusion and spheronization. Three different spheroniser friction plate
      patterns (i.e. cross-hatch, radial, striated edge pattern) have been used in
      order to investigate whether the plate pattern affects physical properties of the
      pellets such as pellet size distribution, yield, shape, mechanical strength,
      density and drug dissolution. Extrusion was performed with a screen extruder and
      the screen size was varied to determine whether the extrudate produced could
      affect the physical properties of pellets. The plate load was also varied.
      Diclofenac sodium was chosen as a model drug. The pattern of the friction plate
      used in the spheronization of extrudates affected the properties of the pellets.
      Yield values varied by up to 20%, and for an otherwise optimised formulation the
      use of a striated edge plate appeared advantageous in this respect. However,
      these pellets had a reduced mechanical strength despite their lower porosity,
      which might be disadvantageous. In addition, other factors such as the amount of
      extrudate loaded into the spheroniser, the maintenance of a constant moisture
      content within the spheroniser and the size of the extruder screen influenced
      these findings significantly. The only physical property of the pellets that did
      not respond to the various changes in the manufacturing process of the pellets is
      the pellet shape, which remained spherical. The dissolution of the drug appeared
      to be related to the median pellet size and was only marginally affected by
      changes in the spheronization process.

PMID- 22659152
TI  - Evolutionary patterns of hind wing morphology in dung beetles (Coleoptera:
      Scarabaeinae).
AB  - The shape of wings can be a good predictor of adaptations to different selective
      pressures and the value of wing features in taxonomy and phylogeny has long been
      recognized. In our investigation of the hind wing evolution of dung beetles
      (Scarabaeinae) we use geometric morphometrics combined with a cladistic approach.
      The variations of entire hind wings and of three specific regions of 80 dung
      beetle species were investigated using 19 landmarks and outline data. Extensive
      evidence indicates that the wing as a whole and the three separate regions were
      under different selective pressures. The detailed evolutionary patterns of the
      three regions and the reconstruction of the ancestral forms were computed by
      mapping the geometric morphometrics data onto a tree based on a cladistic
      character analysis.

PMID- 22659151
TI  - Muscle performance and functional capacity retention in older women after high
      speed power training cessation.
AB  - Power declines more steeply than strength with advancing age and training
      cessation among older women and is associated with the loss of functional
      ability. We tested the hypothesis that the impact of 6 weeks of detraining (DT)
      subsequent to 12 weeks of high-speed power training on maximal strength (1RM) of
      the arm and leg muscles, power performance (counter movement jump and ball
      throwing) and functional task (sit-to-stand test) would decrease physical
      performance, and specifically power performance. Thirty-seven older women were
      divided into an experimental group and a control group [EG, n=20, 65.8 (2.5)
      years; CG: n=17, 64.8 (2.8) years]. Muscular strength, power and functional
      testings were conducted before the initiation of training (T1), after 12 weeks
      (T2) and after 6 weeks of DT (T3). During the 12 weeks of training, EG
      significantly increased their dynamic strength performance (range from 41.9 to
      64.1%), muscle power output (range from 18.2 to 33.6%) (p<0.05) and function
      (15.8%) (p<0.05). No significant differences were observed in the magnitude of
      the increases in CG. Short-term DT led to larger effects on maximal strength
      (18.1-23.8%) (p<0.05) of both upper and lower extremity muscles than in muscle
      power (2-4.5%) and function (2.8%) (p<0.05). However, all measurements remained
      higher (12.6-36.4%; p<0.05) than in pre-training levels. These data indicated
      that DT may induce larger declines in muscle strength than in power output and
      preserved physical independence, mediated in part, by the effectiveness of high
      speed power training particularly developed for older women.

PMID- 22659153
TI  - Cognitive distortions and eating pathology: specificity of thought-shape fusion.
AB  - Thought-shape fusion (TSF) is a cognitive distortion that has been linked with
      eating pathology; however, the specificity of this distortion to eating disorders
      has not yet been examined. The current study set out to investigate the effects
      of a TSF induction on susceptibility to TSF in three groups of women: individuals
      with an eating disorder (n = 33), individuals with obsessive-compulsive disorder
      (OCD; n = 24), and control women with no history of either an eating disorder or
      obsessive-compulsive disorder (n = 26). Participants were assigned to receive
      either a TSF induction or a neutral induction, and their cognitive, emotional,
      and behavioral responses were assessed. As expected, the results demonstrated
      that individuals with eating disorders were more susceptible to TSF than were
      women with OCD and control participants, reporting higher state TSF, more
      negative affect, and more neutralization behavior. The results also supported the
      specificity of this distortion by demonstrating that individuals with OCD were
      not particularly susceptible to TSF. In fact, control participants demonstrated
      an increased susceptibility to TSF relative to women with OCD, as evidenced by
      their higher levels of trait TSF, and increased self-reported distress/difficulty
      in imagining a food-related situation.

PMID- 22659155
TI  - Adherence as a determinant of effectiveness of internet cognitive behavioural
      therapy for anxiety and depressive disorders.
AB  - Since 2009, the Clinical Research Unit for Anxiety and Depression (CRUfAD) has
      been providing primary care clinicians with internet cognitive behaviour therapy
      (iCBT) courses to prescribe to patients. Although these courses have demonstrated
      efficacy in research trials, adherence in primary care is less than half that of
      the research trials. The present studies pose three questions: first, do course
      non-completers drop out because of lack of efficacy? Second, can changes in
      delivery (e.g. adding choice, reminders and financial cost) improve adherence?
      Last, does clinician contact improve adherence? The results showed that non
      completers derive benefit before dropping out; that adding reminders, choice of
      course and timing, and financial cost can significantly improve adherence; and
      that clinician contact during the course is associated with increased adherence.
      It is concluded that improved adherence is an important determinant of
      effectiveness.

PMID- 22659154
TI  - Increasing access to psychological therapies for people with psychosis:
      predictors of successful training.
AB  - BACKGROUND: Cognitive behavioural therapy for psychosis (CBTp) is recommended for
      people with schizophrenia, but routine delivery remains limited. Obstacles to
      increasing access include inadequate training, organisational support and
      supervision, resulting in low levels of staff competence and confidence. This
      study is a preliminary evaluation of a CBTp training programme, designed to
      overcome these obstacles and to increase routine delivery of competent CBTp.
      METHOD: Training outcomes for a pilot group and for the first three cohorts to
      complete training were analysed to identify predictors of successful completion
      and of therapy delivery after training. RESULTS: Objective competence was
      attained by 37 students (out of 58), who delivered therapy to over 160 service
      users. Successful completion was associated with previous CBT therapy experience.
      Delivery after one year was associated with working in a therapy rather than a
      care co-ordination role. CONCLUSIONS: The programme succeeded in training
      therapists to deliver competent therapy. Our results suggest that preliminary
      training in CBT for other disorders may improve success rates in CBTp. Despite
      extensive service liaison, delivery remained problematic for care co-ordinators
      without role change and provision of dedicated time. The findings should inform
      future implementation strategies.

PMID- 22659156
TI  - Longitudinal treatment mediation of traditional cognitive behavioral therapy and
      acceptance and commitment therapy for anxiety disorders.
AB  - OBJECTIVE: To assess the relationship between session-by-session putative
      mediators and treatment outcomes in traditional cognitive behavioral therapy
      (CBT) and acceptance and commitment therapy (ACT) for mixed anxiety disorders.
      METHOD: Session-by-session changes in anxiety sensitivity and cognitive defusion
      were assessed in 67 adult outpatients randomized to CBT (n = 35) or ACT (n = 32)
      for a DSM-IV anxiety disorder. RESULTS: Multilevel mediation analyses revealed
      significant changes in the proposed mediators during both treatments (p < .001, d
      = .90-1.93), with ACT showing borderline greater improvements than CBT in
      cognitive defusion (p = .05, d = .82). Anxiety sensitivity and cognitive defusion
      both significantly mediated post-treatment worry; cognitive defusion more
      strongly predicted worry reductions in CBT than in ACT. In addition, cognitive
      defusion significantly mediated quality of life, behavioral avoidance, and
      (secondary) depression outcomes across both CBT and ACT (p < .05, R(2) change =
      .06-.13), whereas anxiety sensitivity did not significantly mediate other
      outcomes. CONCLUSIONS: Cognitive defusion represents an important source of
      therapeutic change across both CBT and ACT. The data offered little evidence for
      substantially distinct treatment-related mediation pathways.

PMID- 22659157
TI  - Prognostic value of implicit and explicit self-associations for the course of
      depressive and anxiety disorders.
AB  - Dysfunctional self-beliefs are assumed to play an important role in maintaining
      depression and anxiety. Current dual-process models emphasize the relevance of
      differentiating between implicit and explicit self-beliefs. Therefore, this study
      tested the prognostic value of automatic and explicit self-associations for the
      naturalistic course of depressive and anxiety disorders over two years follow-up.
      Both self-depressed and self-anxious associations were measured in unipolar
      depressed patients (n = 313), anxious patients (n = 566), and patients with
      comorbid depressive and anxiety disorders (n = 577) as part of the Netherlands
      Study of Depression and Anxiety. Outcomes showed that in single predictor models
      specifically automatic self-anxious associations were related to a reduced chance
      of remission from anxiety, whereas automatic self-depressed associations were
      related to a reduced chance of remission from depression. Explicit self-anxious
      associations and fearful avoidance behaviour showed independent predictive
      validity for remission from anxiety, whereas explicit self-depressed associations
      and having both major depressive disorder and dysthymia showed independent
      predictive validity for remission from depression. These findings are not only
      consistent with the view that both implicit and explicit dysfunctional self
      associations are related to the course of anxiety and unipolar depressive
      disorders, but also suggest that both types of self-beliefs are proper targets
      for therapeutic interventions.

PMID- 22659158
TI  - Increased wait-list time predicts dropout from outpatient enhanced cognitive
      behaviour therapy (CBT-E) for eating disorders.
AB  - Between 30 and 70% of patients with eating disorders drop out from outpatient
      treatment. However, research has been unable to identify factors that
      consistently predict dropout from eating disorder treatment. Most studies have
      exclusively investigated the role that individual patient characteristics play in
      dropout and have ignored more process-based factors such as expectations about
      treatment, the therapeutic alliance, or time spent on a treatment waiting list.
      This study aimed to investigate the roles of both individual patient
      characteristics and process-based factors in dropout from outpatient treatment
      for eating disorders. The study involved data collected from consecutive eating
      disorder referrals to the only public specialist eating disorder service for
      youth and adults in Perth, Western Australia. The standard treatment provided at
      this service is Enhanced Cognitive Behaviour Therapy on an individual basis. The
      study involved 189 patients referred to the service between 2005 and 2010. Forty
      five percent of this sample dropped out of treatment. Results showed that, in
      this sample, two individual factors, lowest reported weight and the tendency to
      avoid affect, and one process-based factor, time spent on the wait list for
      treatment, were significant predictors of dropout. These findings are valuable
      because a process-based factor, such as wait-list time, may be easier to address
      and modify than a patient's weight history or the trait of mood intolerance.
      Increased resources for eating disorder services may reduce waiting list times
      which would help to reduce dropout and maximize treatment outcomes.

PMID- 22659159
TI  - The influence of context on the implementation of adaptive emotion regulation
      strategies.
AB  - Putatively adaptive emotion regulation strategies (e.g., acceptance, problem
      solving, reappraisal) show weaker associations with psychopathology than
      putatively maladaptive strategies (e.g., avoidance, self-criticism, hiding
      expression, suppression of experience, worry, rumination). This is puzzling,
      given the central role that adaptive strategies play in a wide range of
      psychotherapeutic approaches. We explored this asymmetry by examining the effects
      of context (i.e., emotion intensity, type of emotion, social vs. academic
      circumstances) on the implementation of adaptive and maladaptive strategies. We
      asked 111 participants to describe 8 emotion-eliciting situations and identify
      which strategies they used in order to regulate their affect. We found support
      for a contextual model of emotion regulation, in which adaptive strategies were
      implemented with more cross-situational variability than maladaptive strategies.
      In addition, the variability in implementation of two adaptive strategies
      (acceptance, problem solving) predicted lower levels of psychopathology,
      suggesting that flexible implementation of such strategies in line with
      contextual demands is associated with better mental health. We discuss these
      findings by underscoring the importance of adopting a functional approach to the
      delineation of contextual factors that influence the implementation of emotion
      regulation strategies.

PMID- 22659160
TI  - Health anxiety disorders: a cognitive construal.
AB  - The features of severe health anxiety, intense and persistent anxiety about one's
      present and future health, are described. In common with other anxiety disorders
      such as GAD, PTSD and OCD, the core of HAD is distressing, uncontrollable
      anxiety, and is classifiable as an Anxiety Disorder, Health Anxiety Disorder
      (HAD). The cognitive construal of HAD proposes that health anxiety is caused by
      catastrophic misinterpretations of the significance of sensations and/or changes
      in bodily functions and appearance (such as swellings, pain, loss of energy,
      dizzy spells). The nature, causes, triggers, persistence, assessment and
      treatment of HAD are reviewed, and the present status of the cognitive model is
      appraised. Suggestions are made for future research and clinical applications,
      and the need for incisive evaluations of the main premises of the model is
      emphasized.

PMID- 22659161
TI  - Antimicrobial peptides: clinical relevance and therapeutic implications.
AB  - Antimicrobial peptides (AMPs) are molecules that provide protection against
      environmental pathogens, acting against a large number of microorganisms,
      including bacteria, fungi, yeast, virus and others. Two major groups of
      antimicrobial peptides are found in humans: cathelicidins and defensins.
      Recently, several studies have furnished information that besides their role in
      infection diseases, antimicrobial peptides play a role in diseases as diverse as
      inflammatory disorders, autoimmunity and cancer. Here, we discuss the role of
      antimicrobial peptides and vitamin D have in such complex diseases and propose
      their use should be more explored in the diagnosis and treatment of such
      conditions.

PMID- 22659163
TI  - Phosphorylation of serine-504 of tNOX (ENOX2) modulates cell proliferation and
      migration in cancer cells.
AB  - Tumor-associated NADH oxidase (tNOX; ENOX2) is a growth-related protein expressed
      in transformed cells. Consistent with this function, tNOX knockdown by RNA
      interference leads to a significant reduction in cell proliferation and migration
      in HeLa cells, whereas tNOX overexpression confers an aggressive phenotype. Here,
      for the first time, we report that tNOX is phosphorylated by protein kinase
      Cdelta (PKCdelta) both in vitro and in vivo. Replacement of serine-504 with
      alanine significantly reduces phosphorylation by PKCdelta. Co-immunoprecipitation
      experiments reveal an interaction between tNOX and PKCdelta. Moreover, whereas
      overexpression of wild-type tNOX in NIH3T3 cells increases cell proliferation and
      migration, overexpression of the S504A tNOX mutant leads to diminished cell
      proliferation and migration, reflecting reduced stability of the
      unphosphorylatable tNOX mutant protein. Collectively, these results suggest that
      phosphorylation of serine-504 by PKCdelta modulates the biological function of
      tNOX.

PMID- 22659162
TI  - Atorvastatin preserves the integrity of endothelial adherens junctions by
      inhibiting vascular endothelial cadherin tyrosine phosphorylation.
AB  - Vascular endothelial cadherin (VE-cad) tyrosine (Tyr) phosphorylation has been
      implicated in the disruption of adherens junctions (AJs) induced by inflammatory
      reactions. The impacts of statins on integrity of AJs and VE-cad Tyr
      phosphorylation have not been explored. The effects of atorvastatin on IL-1beta
      and monocyte-induced VE-cad Tyr phosphorylation in human umbilical vein
      endothelial cells (ECs) were studied. In ECs treated with interleukin (IL)-1beta
      for 30 min, VE-cad Tyr phosphorylation, dissociation of the VE-cad/beta-catenin
      complex and transendothelial migration (TEM) of monocytes were increased. These
      processes were mediated by activation of HRas and RhoA that leads to
      phosphorylation of myosin light chain (MLC). Atorvastatin inhibited IL-1beta
      induced Tyr phosphorylation of VE-cad by inhibiting RhoA and by dephosphorylating
      MLC. The attenuating effect of atorvastatin on VE-cad Tyr phosphorylation was
      reversed when RhoA was activated or MLC phosphatase was inhibited. Furthermore,
      inhibiting farnesyl transferase or geranylgeranyl transferase reproduced the
      inhibitory effects of atorvastatin on VE-cad Tyr phosphorylation. In addition,
      atorvastatin inhibited monocyte-induced VE-cad Tyr phosphorylation in ECs and
      attenuated IL-1beta-induced TEM of monocytes. Our study introduces a novel
      pleiotropic effect of atorvastatin and suggests that statins protect the
      integrity of AJs in ECs by inhibiting RhoA-mediated Tyr phosphorylation of VE
      cad.

PMID- 22659164
TI  - CLP36 and RIL recruit alpha-actinin-1 to stress fibers and differentially
      regulate stress fiber dynamics in F2408 fibroblasts.
AB  - CLP36 is a member of the ALP/Enigma protein family and has been shown to be
      localized to stress fibers in various cells. We previously reported that
      depletion of CLP36 caused loss of stress fibers in BeWo choriocarcinoma cells,
      but it remains unclear how CLP36 contributes to stress fiber formation. In this
      study, we generated CLP36-depleted F2408 fibroblasts and found that stress fibers
      showed abnormal non-oriented organization in these cells. In addition to CLP36,
      F2408 cells contained RIL, another ALP/Enigma protein, and we demonstrated that
      RIL could compensate for the role of CLP36 in stress fiber formation. CLP36 and
      RIL form a complex with alpha-actinin-1 and palladin. We found a strong
      correlation between loss of CLP36/RIL and failure of alpha-actinin-1 or palladin
      to localize on stress fibers. In addition, time lapse observation revealed that
      incorporation of RIL stabilizes stress fibers and that CLP36 influences the
      dynamic architecture of these fibers. Our findings indicate that CLP36 and RIL
      have a redundant role in the formation of stress fibers, but have different
      effects on stress fiber dynamics in F2408 cells.

PMID- 22659165
TI  - VEGF induces proliferation of human hair follicle dermal papilla cells through
      VEGFR-2-mediated activation of ERK.
AB  - Vascular endothelial growth factor (VEGF) is one of the strongest regulators of
      physiological and pathological angiogenesis. VEGF receptor 2 (VEGFR-2), the
      primary receptor for VEGF, is thought to mediate major functional effects of
      VEGF. Previously, we have localized both VEGF and VEGFR-2 in human hair
      follicles. In this study, we further defined the expression and roles of VEGFR-2
      on human hair follicle dermal papilla (DP) cells. The expression of VEGFR-2 on DP
      cells was examined by reverse transcription-polymerase chain reaction (RT-PCR)
      and Western blot analysis separately, and localization of VEGFR-2 was defined by
      immunofluorescence. The effect of VEGF on DP cells was analyzed by MTT assays and
      specific inhibitors. Finally, the role of VEGF involved in the signaling pathways
      was investigated by Western blot. RT-PCR and Western blot analysis demonstrated
      the expression of VEGFR-2 on DP cells. Immunostaining for VEGFR-2 showed strong
      signal on cultured human DP cells in vitro. Exogenous VEGF(165) stimulated
      proliferation of DP cells in a dose-dependent manner. Furthermore, this
      stimulation was blocked by a VEGFR-2 neutralizing antibody (MAB3571) and an ERK
      inhibitor (PD98059). VEGF(165)-induced phosphorylation of ERK1/2 was abolished by
      MAB3571 and PD98059, while the phosphorylation of p38, JNK and AKT were not
      changed by VEGF(165). Taken together, VEGFR-2 is expressed on primary human hair
      follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK
      pathway, but not p38, JNK or AKT signaling.

PMID- 22659166
TI  - Force-dependent bond dissociation govern rolling of HL-60 cells through E
      selectin.
AB  - E-selectin-mediated rolling on vascular surface of circulating leukocyte on
      vascular surface is a key initial event during inflammatory response and
      lymphocyte homing. This event depends not only on the specific interactions of
      adhesive molecules but also on the hemodynamics of blood flow. Little is still
      understood about whether wall shear stress or shear rate regulates the rolling.
      With flow chamber techniques, we here measured the effects of transport, shear
      stress and cell deformation on rolling of both unfixed and fixed HL-60 cells on E
      selectin either in the absence or in the presence of 3% Ficoll in medium at
      various wall shear stresses from 0.05 to 0.7 dyn/cm(2). The results demonstrated
      a triphasic force-dependent rolling, that is, as increasing of force, the rolling
      would be accelerated firstly, then followed a decelerating phase occurred at the
      initial shear threshold of about 0.1 dyn/cm(2), and lastly returned to an
      accelerating process starting at the optimal shear threshold of 0.35 dyn/cm(2)
      approximately. The catch bond regime was completely reflected to rolling
      behaviors, such as tether lifetime, cell stop time and rolling velocity, meaning
      that the dominant factor to govern rolling is force. The initial shear threshold
      might be the minimum level of wall shear stress to sustain a stationary rolling,
      and the optimal shear threshold would make rolling to the most stable and
      regular. These findings strongly elucidate the catch bond mechanism for flow
      enhanced rolling through E-selectin since longer bond lifetimes led to slower and
      stabler rolling.

PMID- 22659168
TI  - Rho GTPase function in development: how in vivo models change our view.
AB  - Rho GTPase functions have been carefully investigated for many years using cell
      biological models. In recent years, mouse models with targeted mutations in Rho
      GTPase genes enabled the study of Rho GTPase function in vivo, partially
      confirming and partially contradicting expectations based on earlier in vitro
      experiments. This review sums up recent findings on the role of Rho GTPases in
      development, underlining the importance of in vivo research for our understanding
      of Rho GTPases in living organisms, and describing challenges for the future.

PMID- 22659169
TI  - Morphological, molecular and functional differences of adult bone marrow- and
      adipose-derived stem cells isolated from rats of different ages.
AB  - Adult mesenchymal stem cells have self-renewal and multiple differentiation
      potentials, and play important roles in regenerative medicine. However, their use
      may be limited by senescence or age of the donor, leading to changes in stem cell
      functionality. We investigated morphological, molecular and functional
      differences between bone marrow-derived (MSC) and adipose-derived (ASC) stem
      cells isolated from neonatal, young and old rats compared to Schwann cells from
      the same animals. Immunocytochemistry, RT-PCR, proliferation assays, western
      blotting and transmission electron microscopy were used to investigate expression
      of senescence markers. Undifferentiated and differentiated ASC and MSC from
      animals of different ages expressed Notch-2 at similar levels; protein-38 and
      protein-53 were present in all groups of cells with a trend towards increased
      levels in cells from older animals compared to those from neonatal and young
      rats. Following co-culture with adult neuronal cells, dMSC and dASC from animals
      of all ages elicited robust neurite outgrowth. Mitotracker((r)) staining was
      consistent with ultrastructural changes seen in the mitochondria of cells from
      old rats, indicative of senescence. In conclusion, this study showed that
      although the cells from aged animals expressed markers of senescence, aged MSC
      and ASC differentiated into SC-like cells still retain potential to support axon
      regeneration.

PMID- 22659167
TI  - CD147 and AGR2 expression promote cellular proliferation and metastasis of head
      and neck squamous cell carcinoma.
AB  - The signaling pathways facilitating metastasis of head and neck squamous cell
      carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane
      glycoprotein known to induce cell migration and invasion. AGR2 is a secreted
      peptide also known to promote cell metastasis. Here we describe their importance
      in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in
      vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation,
      migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased
      primary tumor growth as well as regional and distant metastasis.

PMID- 22659170
TI  - Autoimmune regulator is acetylated by transcription coactivator CBP/p300.
AB  - The Autoimmune Regulator (AIRE) is a regulator of transcription in the thymic
      medulla, where it controls the expression of a large set of peripheral-tissue
      specific genes. AIRE interacts with the transcriptional coactivator and
      acetyltransferase CBP and synergistically cooperates with it in transcriptional
      activation. Here, we aimed to study a possible role of AIRE acetylation in the
      modulation of its activity. We found that AIRE is acetylated in tissue culture
      cells and this acetylation is enhanced by overexpression of CBP and the CBP
      paralog p300. The acetylated lysines were located within nuclear localization
      signal and SAND domain. AIRE with mutations that mimicked acetylated K243 and
      K253 in the SAND domain had reduced transactivation activity and accumulated into
      fewer and larger nuclear bodies, whereas mutations that mimicked the unacetylated
      lysines were functionally similar to wild-type AIRE. Analogously to CBP, p300
      localized to AIRE-containing nuclear bodies, however, the overexpression of p300
      did not enhance the transcriptional activation of AIRE-regulated genes. Further
      studies showed that overexpression of p300 stabilized the AIRE protein.
      Interestingly, gene expression profiling revealed that AIRE, with mutations
      mimicking K243/K253 acetylation in SAND, was able to activate gene expression,
      although the affected genes were different and the activation level was lower
      from those regulated by wild-type AIRE. Our results suggest that the AIRE
      acetylation can influence the selection of AIRE activated genes.

PMID- 22659171
TI  - Long time monitoring of the respiratory activity of isolated mitochondria.
AB  - We have investigated the ability of optical oxygen sensors incorporated in a
      microplate to determine the respiratory activity of cell fractions. Different
      cell fractions were monitored, in particular to evaluate the long term
      functionality of isolated mitochondria. It is possible to continuously sense
      respiratory activity of isolated mitochondria over time. We found that they are
      functional for three hours but stop respiring at a critical limit of 20% air
      saturation in the system. Furthermore, inhibition and enhancement of respiratory
      activity were detected. In conclusion, oxygen sensors are a powerful tool to
      evaluate the functionality of isolated mitochondria.

PMID- 22659172
TI  - Processing and in vivo evaluation of multiphasic calcium phosphate cements with
      dual tricalcium phosphate phases.
AB  - Calcium phosphate cements (CPCs) use the simultaneous presence of several calcium
      phosphates phases. This is done to generate specific bulk and in vivo properties.
      This work has processed and evaluated novel multiphasic CPCs containing dual
      tricalcium phosphate (TCPs) phases. Dual TCPs containing alpha- and beta-TCP
      phases were obtained by thermal treatment. Standard CPC (S-CPC) was composed of
      alpha-TCP, anhydrous dicalcium phosphate and precipitated hydroxyapatite, while
      modified CPC (DT-CPC) included both alpha- and beta-TCP. Physicochemical
      characterization of these CPCs was based on scanning electron microscopy, X-ray
      diffraction, specific surface area (SSA) and particle size (PS) analysis and
      mechanical properties. This characterization allowed the selection of one DT-CPC
      for setting time, cohesion and biological assessment compared with S-CPC.
      Biological assessment was carried out using a tibial intramedullary cavity model
      and subcutaneous pouches in guinea pigs. Differences in the surface morphology
      and crystalline phases of the treated TCPs were detected, although PS analysis of
      the milled CPC powders produced similar results. SSA analysis was significantly
      higher for DT-CPC with alpha-TCP treated at 1100 degrees C for 5h. Poorer
      mechanical properties were found for DT-CPC with alpha-TCP treated at 1000
      degrees C. Setting time and cohesion, as well as the in vivo performance, were
      similar in the selected DT-CPC and the S-CPC. Both CPCs created the desired host
      reactions in vivo.

PMID- 22659174
TI  - Bioactive starch-based scaffolds and human adipose stem cells are a good
      combination for bone tissue engineering.
AB  - Silicon is known to have an influence on calcium phosphate deposition and on the
      differentiation of bone precursor cells. This study explores the effect of the
      incorporation of silanol (Si-OH) groups into polymeric scaffolds on the
      osteogenic differentiation of human adipose stem cells (hASC) cultured under
      dynamic and static conditions. A blend of corn starch with polycaprolactone
      (30/70 wt.%, SPCL) was used to produce three-dimensional fibre meshes scaffolds
      by the wet-spinning technique, and a calcium silicate solution was used as a non
      solvent to develop an in situ functionalization with Si-OH groups. In vitro
      assessment, using hASC, of functionalized and non-functionalized scaffolds was
      evaluated in either alpha-MEM or osteogenic medium under static and dynamic
      conditions (provided by a flow perfusion bioreactor). The functionalized
      materials, SPCL-Si, exhibit the capacity to sustain cell proliferation and induce
      their differentiation into the osteogenic lineage. The formation of
      mineralization nodules was observed in cells cultured on the SPCL-Si materials.
      Culturing under dynamic conditions using a flow perfusion bioreactor was shown to
      enhance the hASC proliferation and differentiation and a better distribution of
      cells within the material. The present work demonstrates the potential of these
      functionalized materials for future applications in bone tissue engineering.
      Additionally, these results highlight the simplicity, economic and reliable
      production process of those materials.

PMID- 22659175
TI  - A new dextran-graft-polybutylmethacrylate copolymer coated on 316L metallic
      stents enhances endothelial cell coverage.
AB  - Amphiphilic copolymers based on the copolymerization of hydrophilic and
      hydrophobic moieties offer versatility in various biomedical material
      applications. Here, a new biocompatible copolymer of dextran-graft
      polybutylmethacrylate is synthesized for the coating of metallic endovascular
      stents. Coating of metallic surfaces is performed and analyzed by X-ray
      photoelectron spectroscopy, attenuated total reflection Fourier transform
      infrared spectroscopy, contact angle measurement, atomic force microscopy and
      scanning electron microscopy before and after deformation corresponding to stent
      deployment by a balloon catheter. In the conditions described here, the resulting
      coating is smooth and uniform with neither cracks nor detachment after stent
      expansion. Interestingly, surfaces coated with the copolymer greatly improve in
      vitro adhesion and growth of endothelial cells. This copolymer provides new
      opportunities for implanted biomaterials.

PMID- 22659173
TI  - Quaternary ammonium silane-functionalized, methacrylate resin composition with
      antimicrobial activities and self-repair potential.
AB  - The design of antimicrobial polymers to address healthcare issues and minimize
      environmental problems is an important endeavor with both fundamental and
      practical implications. Quaternary ammonium silane-functionalized methacrylate
      (QAMS) represents an example of antimicrobial macromonomers synthesized by a sol
      gel chemical route; these compounds possess flexible Si-O-Si bonds. In present
      work, a partially hydrolyzed QAMS co-polymerized with 2,2-[4(2-hydroxy 3
      methacryloxypropoxy)-phenyl]propane is introduced. This methacrylate resin was
      shown to possess desirable mechanical properties with both a high degree of
      conversion and minimal polymerization shrinkage. The kill-on-contact
      microbiocidal activities of this resin were demonstrated using single-species
      biofilms of Streptococcus mutans (ATCC 36558), Actinomyces naeslundii (ATCC
      12104) and Candida albicans (ATCC 90028). Improved mechanical properties after
      hydration provided the proof-of-concept that QAMS-incorporated resin exhibits
      self-repair potential via water-induced condensation of organic modified silicate
      (ormosil) phases within the polymerized resin matrix.

PMID- 22659177
TI  - Biodistribution of polymer hydrogel capsules for the delivery of therapeutics.
AB  - A key phase in the development of intelligently designed nanoparticle delivery
      vehicles for new therapeutic agents is to gain an understanding of their
      interaction with tissues and cells. We report a series of in vitro and in vivo
      experiments aimed at tracking a potential delivery vehicle for therapeutic
      agents, including vaccine peptides and drugs derived from poly(methacrylic acid)
      hydrogel capsules in certain organs and cell types. For the in vitro studies, two
      immortal liver-derived cell lines (Huh7 and Hepa1-6) and primary cultures of
      mouse hepatocytes were incubated with Alexa 647 labelled fluorescent capsules to
      track their internalization and intracellular distribution by confocal
      microscopy. Capsules, 500nm in diameter, were taken up into the cells in a time
      dependent manner in all three cell lines. Capsules were observed in plasma
      membrane-derived vesicles within the cells. After 24h a significant proportion of
      the capsules was observed in lysosomes. To understand the behaviour of the
      capsules in vivo, Alexa 488 labelled fluorescent capsules were intravenously
      injected into Sprague-Dawley rats and after 24h the fate of the capsules in a
      number of organs was determined by flow cytometry and confocal microscopy. By
      flow cytometry, the majority of the capsules were detected in the spleen whilst
      similar numbers were found in the lung and liver. By confocal microscopy, the
      majority of the capsules were found in the liver and spleen with significantly
      less capsules in the lung, heart and kidney. Colocalization of capsules with cell
      type specific markers indicated that in lung, heart and kidney, the majority of
      the capsules were located in endothelial cells. In the spleen ~50% of the
      capsules were found in CD163-positive cells, whereas in the liver, almost all
      capsules were located in CD163-positive cells, indicating uptake by Kupffer
      cells. Electron microscopy confirmed the presence of capsules within Kupffer
      cells.

PMID- 22659176
TI  - Tunable hydrogel-microsphere composites that modulate local inflammation and
      collagen bulking.
AB  - Injectable biomaterials alone may alter local tissue responses, including
      inflammatory cascades and matrix production (e.g. stimulatory dermal fillers are
      used as volumizing agents that induce collagen production). To expand upon the
      available material compositions and timing of presentation, a tunable hyaluronic
      acid (HA) and poly(lactide-co-glycolide) (PLGA) microsphere composite system was
      formulated and assessed in subcutaneous and cardiac tissues. HA functionalized
      with hydroxyethyl methacrylate (HeMA) was used as a precursor to injectable and
      degradable hydrogels that carry PLGA microspheres (~50 MUm diameter) to tissues,
      where the HA hydrogel degradation (~20 or 70 days) and quantity of PLGA
      microspheres (0-300 mgml(-1)) are readily varied. When implanted subcutaneously,
      faster hydrogel degradation and more microspheres (e.g. 75 mgml(-1)) generally
      induced more rapid tissue and cellular interactions and a greater macrophage
      response. In cardiac applications, tissue bulking may be useful to alter stress
      profiles and to stabilize the tissue after infarction, limiting left ventricular
      (LV) remodeling. When fast degrading HeMA-HA hydrogels containing 75 mgml(-1)
      microspheres were injected into infarcted tissue in sheep, LV dilation was
      limited and the thickness of the myocardial wall and the presence of vessels in
      the apical infarct region were increased ~35 and ~60%, respectively, compared to
      empty hydrogels. Both groups decreased volume changes and infarct areas at 8
      weeks, compared to untreated controls. This work illustrates the importance of
      material design in expanding the application of tissue bulking composites to a
      range of biomedical applications.

PMID- 22659178
TI  - Degradation and drug release in calcium polyphosphate bioceramics: an MRI-based
      characterization.
AB  - Degradable, bioceramic bone implants made of calcium polyphosphate (CPP) hold
      potential for controlled release of therapeutic agents in the treatment of
      localized bone disease. Magnetic resonance imaging techniques for non-invasively
      mapping fluid distribution, T(1) and T(2) relaxation times and the apparent
      diffusion coefficient were performed in conjunction with a drug elution protocol
      to resolve free and bound water components within the material microstructure in
      two CPP formulations (G1 and G2). The T(2) maps provided the most accurate
      estimates of free and bound water, and showed that G1 disks contained a
      detectable free water component at all times, with drug release dominated by a
      Fickian diffusion mechanism. Drug release from G2 disks was characterized by a
      combined diffusional/structural relaxation mechanism, which may be related to the
      gradual infiltration of a free water component associated with swelling and/or
      chemical degradation.

PMID- 22659179
TI  - Functionalization of dynamic culture surfaces with a cartilage extracellular
      matrix extract enhances chondrocyte phenotype against dedifferentiation.
AB  - Culture on silicone rubber surfaces has been shown to partially overcome the
      chondrocyte dedifferentiation characteristic of standard culture on rigid
      polystyrene. These methods typically involve functionalization of culture
      surfaces with proteins. Collagen type I is often used, but more cartilage
      specific proteins may be more appropriate for chondrocytes. To explore this
      hypothesis, a twofold experimental design was applied. First, chondrocytes were
      cultured in rigid Petri dishes coated with silicone rubber ("static silicone" or
      SS culture) functionalized with either cartilage extracellular matrix (ECM)
      extract or collagen type I. Second, chondrocytes were cultured on monotonically
      expanded high extension silicone rubber dishes ("continuous expansion" or CE
      culture) functionalized with ECM extract and compared to cells grown in SS
      culture. There were no differential effects of surface functionalization with the
      ECM extract vs. collagen type I on chondrocyte morphology, viability,
      proliferation or apoptosis in SS culture. However, chondrocyte growth on the ECM
      extract was associated with significantly reduced collagen types I and X gene
      expression and significantly increased glycosaminoglycan (GAG) secretion. After 3
      passages (P3) on ECM-coated SS culture, chondrocyte phenotype and GAG secretion
      was enhanced compared to cells passaged on collagen type I. Pellet cultures from
      P3 SS culture displayed enhanced collagen type II content when ECM extract was
      used for functionalization rather than collagen type I. In CE culture with ECM
      functionalization, chondrocyte dedifferentiation was significantly inhibited vs.
      SS cultures, as evidenced by both gene expression and pellet cultures.
      Functionalization of extendable culture surfaces with cartilage ECM extract
      therefore supports enhanced preservation of chondrocyte phenotype.

PMID- 22659180
TI  - Plasmid integration method: a new tool for analysis of the essentiality and
      function of genes in S. aureus.
AB  - Staphylococcus aureus is a Gram-positive coccus and one of the major causes of
      community-acquired and hospital-acquired infections. We established the
      convenient and reliable experimental system for analyzing the essentiality and
      function of genes, the plasmid integration (PI) method. This method is based on
      plasmid integration into the genome by single cross-over recombination using a
      temperature-sensitive shuttle vector, and it was validated using known essential
      genes, gyrA and mvaD, and non-essential genes, sigB and hla. Then we analyzed 116
      S. aureus conserved hypothetical protein genes with the PI method, and identified
      28 essential genes. Moreover, applying the PI method, we confirmed the functional
      redundancy between the S. aureus gene (SA0865) and its ortholog human gene, the
      NAD kinase gene. These results show that the PI method is a powerful tool for the
      identification of essential genes and functional analysis by evaluation of
      complementarity.

PMID- 22659181
TI  - Analysis of TGFB1 in European and Japanese Moyamoya disease patients.
AB  - BACKGROUND: Despite large efforts in researching the genesis of Moyamoya disease
      (MMD), the etiology of this rare disease remains widely unknown. In a previous
      publication we described two genetic variants in the first exon of transforming
      growth factor beta 1 (TGFB1) which were associated and showed a tendency toward
      significance, respectively. In this study we performed a follow-up analysis of
      TGFB1 by sequencing the complete exon 1 in European and by genotyping previously
      described positively associated single nucleotide polymorphisms (SNPs) in
      Japanese patients with MMD. METHODS: The complete first exon of TGFB1 was
      genotyped in 40 MMD patients and 68 healthy controls from central Europe. For
      verification, genotyping of the previously described SNPs rs1800470 and rs1800471
      was performed in 45 Japanese MMD patients and 79 healthy controls. Analysis was
      performed by capillary sequencing with custom made primers. RESULTS: Sequencing
      of the first exon of TGFB1 in the European cohort did not reveal any new disease
      associated nor other genetic variations. The previously described disease
      association of rs1800471 and tendency toward significance of rs1800470 could not
      be replicated in the Japanese cohort. CONCLUSIONS: As no new genetic variants
      were uncovered in this study of the first exon of TGFB1 in European MMD patients
      and because of the negative association of rs1800470 and rs1800471 in Japanese
      MMD patients, a role of this exon of TGFB1 in the genesis of MMD is unlikely.
      Further analyses with even larger cohorts may be necessary to detect causal
      genetic factors that contribute to the genesis of this disease.

PMID- 22659182
TI  - SHORT VEGETATIVE PHASE (SVP) protein negatively regulates miR172 transcription
      via direct binding to the pri-miR172a promoter in Arabidopsis.
AB  - Plant microRNAs (miRNAs) are non-coding RNAs that negatively regulate expression
      of their target genes. Although much is known about miRNA biogenesis and
      repression of target genes by miRNAs, the molecular mechanisms underlying the
      transcriptional regulation of miRNA itself are poorly understood. Here, we report
      that SHORT VEGETATIVE PHASE (SVP) protein is a direct transcriptional regulator
      of miR172. The levels of mature miR172 and pri-miR172a were anti-correlated with
      SVP activity. miR172a has multiple transcription start sites, among which the
      transcript starting with cytosine (-671bp, relative to the mature miR172a) was a
      major species. EMSA and ChIP analysis demonstrated that SVP protein binds to the
      CArG motifs in the miR172a promoter. These results suggest that SVP protein
      directly regulates miR172 transcription in Arabidopsis.

PMID- 22659183
TI  - HSC90 is required for nascent hepatitis C virus core protein stability in yeast
      cells.
AB  - Hepatitis C virus core protein (Core) contributes to HCV pathogenicity. Here, we
      demonstrate that Core impairs growth in budding yeast. We identify HSP90
      inhibitors as compounds that reduce intracellular Core protein level and restore
      yeast growth. Our results suggest that HSC90 (Hsc82) may function in the
      protection of the nascent Core polypeptide against degradation in yeast and the C
      terminal region of Core corresponding to the organelle-interaction domain was
      responsible for Hsc82-dependent stability. The yeast system may be utilized to
      select compounds that can direct the C-terminal region to reduce the stability of
      Core protein.

PMID- 22659185
TI  - Genetically encoded RNA photoswitches as tools for the control of gene
      expression.
AB  - An important goal in chemical and synthetic biology is controlling the expression
      of defined sets of genes by external stimuli, and one of the most attractive
      stimuli is light. Current approaches to the photocontrol of biological processes
      utilize photoresponsive proteins. In this article, I will illustrate the
      prospects of synthetic systems in which the receptor is a photoresponsive nucleic
      acid, and will review the different tools already in place to develop
      photoresponsive systems based on RNA. A particular focus is on genetically
      encoded photoswitches that can be expressed in prokaryotic or eukaryotic cells,
      and respond to photoisomerizable, cell-permeable small molecules.

PMID- 22659184
TI  - Mutational analysis reveals a dual role of Mdm2 acidic domain in the regulation
      of p53 stability.
AB  - The exact role of the central acidic domain of Mdm2 in p53 degradation remains
      unclear. We therefore performed a systematic and comprehensive analysis of the
      acidic domain using a series of short deletions and found that only a minor part
      of the domain was indispensable for Mdm2-mediated p53 ubiquitylation. Moreover,
      we identified a short stretch of acidic amino acids required for p53 degradation
      but not ubiquitylation, indicating that, in addition to p53 ubiquitylation, the
      acidic domain might be involved in a critical post-ubiquitylation step in p53
      degradation. Rather than representing a single functional domain, different parts
      of the acidic region perform separate functions in p53 degradation, suggesting
      that it might be possible to therapeutically target them independently.

PMID- 22659186
TI  - Significant energy transfer from CpcG2-phycobilisomes to photosystem I in the
      cyanobacterium Synechococcus sp. PCC 7002 in the absence of ApcD-dependent state
      transitions.
AB  - Hemidiscoidal phycobilisomes (PBS), the major light harvesting complexes of
      photosynthesis in most cyanobacteria, are composed of rods and cores, which are
      linked by the linker CpcG1 (L(RC)). Another type of PBS, CpcG2-PBS exits and
      their function in energy transfer has not been fully understood. We measured
      growth rates, absorption cross-sections and quantum efficiency of photosystem I
      in mutant strains of Synechococcus PCC sp. 7002 lacking the linker CpcG2. Our
      results showed that energy transfer from CpcG2-PBS to PSI in the absence of state
      transitions could be significant under PBS-absorbing light and energy transfer
      from two types of PBS is independent to each other. Evidence also suggested that
      CpcG2 anchors the CpcG2-PBS to thylakoid membranes.

PMID- 22659187
TI  - The protease-activated receptor 1 possesses a functional and cleavable signal
      peptide which is necessary for receptor expression.
AB  - The protease-activated receptor 1 (PAR1) is activated by thrombin cleavage
      releasing the physiologically-relevant parstatin peptide (residues 1-41).
      However, the actual length of parstatin was unclear since the receptor may also
      possess a cleavable signal peptide (residues 1-21) according to prediction
      programs. Here, we show that this putative signal peptide is indeed functional
      and removed from the PAR1 resolving the question of parstatin length. Moreover,
      we show that the sequence encoding the signal peptide may surprisingly play a
      role in stabilization of the PAR1 mRNA, a function which would be novel for a G
      protein-coupled receptor.

PMID- 22659188
TI  - Non-enzymatic conversion of chlorophyll-a into chlorophyll-d in vitro: a model
      oxidation pathway for chlorophyll-d biosynthesis.
AB  - Chlorophyll-a (Chl-a) was readily converted into Chl-d under mild conditions
      without any enzymes. Treatment of Chl-a dissolved in dry tetrahydrofuran (THF)
      with thiophenol and acetic acid at room temperature successfully produced Chl-d
      in 31% yield. During the acidic oxidation, removal of the central magnesium,
      pheophytinization, was sufficiently suppressed. This mild pathway can give
      insights into the yet unidentified Chl-d biosynthesis.

PMID- 22659189
TI  - Syndecans play dual roles as cell adhesion receptors and docking receptors.
AB  - Syndecan are a family of cell surface heparan sulfate proteoglycans that act as
      cell surface receptors. Most cell surface receptors have a limited number and
      type of ligand interactions, responding only to the binding of (a) specific
      ligand(s). In contrast, syndecans can interact with various numbers and types of
      ligands, and thus play more diverse roles than others. Various syndecan functions
      have not yet been fully classified and categorized, but we herein review previous
      studies suggesting that syndecans play dual function as cell surface receptors by
      acting as both adhesion receptors and docking receptors. Through this dual
      regulatory function, syndecans are capable of regulating both intra- and
      extracellular activities, potentially altering a variety of cell behaviors.

PMID- 22659190
TI  - A phase II clinical trial of pegylated liposomal doxorubicin and carboplatin plus
      bevacizumab in patients with platinum-sensitive recurrent ovarian, fallopian
      tube, or primary peritoneal cancer.
AB  - OBJECTIVE: To assess the safety and efficacy of pegylated liposomal doxorubicin
      (PLD), carboplatin, plus bevacizumab in patients with ovarian, fallopian tube, or
      primary peritoneal cancer. METHODS: Patients with platinum-sensitive, recurrent
      disease received PLD 30 mg/m(2) and carboplatin area under the curve (AUC) 5 on
      Day 1 plus bevacizumab 10mg/kg on Days 1 and 15 of every 28-day cycle, for a
      maximum of 10 cycles. The primary endpoint was objective response rate (ORR)
      [complete+partial response]; additional endpoints were safety, duration of
      response, progression-free survival (PFS), and time to progression (TTP).
      RESULTS: Of the 54 patients enrolled, 15 (27.8%) completed the study treatment as
      planned. Intent-to-treat (all enrolled patients) ORR was 72.2% (95% CI: 58.4,
      83.5). Median duration of response was 11.9 months (95% CI: 9.3, not estimable)
      and median TTP was 13.9 months (95% CI: 11.4, 16.0). PFS was virtually the same
      as TTP. Three (5.6%) patients discontinued therapy due to disease progression,
      and another 3 (5.6%) patients discontinued therapy due to serious adverse events
      (Grade 4 thrombocytopenia, Grade 3 small/large intestinal obstruction/small
      intestinal perforation, and Grade 3 abdominal abscess). Fifty (92.6%) patients
      had >=1 adverse event of interest, most commonly neutropenia (42.6%),
      hypertension (37.0%), stomatitis (37.0%), proteinuria (37.0%), and palmar-plantar
      erythrodysesthesia (27.8%). No appreciable decreases in left-ventricular ejection
      fraction were observed. CONCLUSION: Most patients responded to PLD, carboplatin,
      and bevacizumab combination therapy. The safety profile was consistent with the
      known toxicities of these agents. These findings present a potential treatment
      option for women with ovarian, fallopian tube, or primary peritoneal cancer.

PMID- 22659191
TI  - Management of complex pelvic masses using a multivariate index assay: a decision
      analysis.
AB  - OBJECTIVE: To develop a cost-minimization analysis of a multivariate index assay
      (MIA) used for women with complex pelvic masses. METHODS: A decision analysis
      model was used to evaluate 81,000 hypothetical patients with a complex pelvic
      mass requiring surgery. Three strategies were evaluated: (1) referral to a
      gynecologic oncologist (GO) based on clinical assessment including physical exam,
      ultrasonography, and CA125 (CLINICAL); (2) utilization of a multivariate index
      assay (MIA); or (3) referral of all patients to a GO (REFER ALL). Various
      reoperation rates were evaluated with sensitivity analyses. Actual payer costs
      were compared between each strategy. RESULTS: The CLINICAL strategy cost $933.9
      million (M) and resulted in 72% of patients receiving appropriate initial
      surgical staging. The REFER ALL strategy cost $939.7 M and all patients were
      appropriately staged. The MIA strategy cost $976.7 M and resulted in 91% of
      patients having appropriate initial staging. Using conservative reoperation rates
      (10-20%), 461 patients required reoperation using CLINICAL strategy compared to
      142 patients in MIA strategy. Using aggressive reoperation rates (40-50%), 1715
      patients required reoperation using CLINICAL strategy resulting in an incremental
      cost of $15.2M compared to 529 patients at $4.7 M in MIA strategy. The increased
      costs associated with an aggressive reoperation rate resulted in the REFER ALL
      strategy being the least expensive alternative, with the highest rates of
      appropriate initial surgery. CONCLUSIONS: Utilizing an MIA resulted in more
      ovarian cancer patients receiving appropriate initial surgery, but at increased
      costs. Referring all patients with complex masses avoids the most reoperations at
      reduced cost compared to using an MIA.

PMID- 22659192
TI  - Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic
      injection of radiolabeled tracer.
AB  - OBJECTIVE: Retrospective and perspective series have shown the feasibility of
      sentinel lymph-node (SLN) identification of pelvic nodes in endometrial cancer
      using a cervical injection of tracers. We designed a perspective study to assess
      the detection rate and diagnostic accuracy of the SLN procedure by means of
      hysteroscopic injection of a radiolabeled tracer in endometrial cancer patients.
      METHODS: Patients with endometrial cancer underwent hysteroscopic technetium
      injection. SLN assessment was performed intraoperatively. A systematic pelvic and
      paraaortic dissection was carried out thereafter. SLNs were examined by standard
      and immunochemistry methods. The primary endpoint was estimation of sensitivity
      and negative predictive value (NPV) of sentinel-node biopsy. RESULTS: From 2005
      to 2010, 80 consecutive patients entered the study. No severe complications
      occurred during or after the injection or during surgical SLN biopsy. At least
      one SLN was detected in 76 of the 80 eligible patients. Fifty nine patients were
      evaluable according to the study protocol. Ten of these patients (17%) had node
      metastases. Thirty-three patients (56%) had SLN in the para-aortic area. NPV was
      98% (95% CI 89.4-100) and sensitivity 90% (55.5-99.8). CONCLUSIONS: SLN detection
      for endometrial cancer patients has a high sensitivity and NPV when injection is
      carried out by hysteroscopy. The occurrence of a 56% of sentinel node in
      paraaortic area may suggest a better sensitivity in this area using hysteroscopic
      injection compared to cervical injection.

PMID- 22659193
TI  - Patterns of recurrence in advanced epithelial ovarian, fallopian tube and
      peritoneal cancers treated with intraperitoneal chemotherapy.
AB  - OBJECTIVES: To examine the distribution and outcomes of recurrent disease in
      patients with ovarian, fallopian tube and peritoneal cancers after optimal
      cytoreduction and adjuvant intraperitoneal (IP) chemotherapy. METHODS: All
      patients diagnosed with ovarian, fallopian tube, or peritoneal cancer between
      2004 and 2009 who underwent optimal cytoreductive surgery and received adjuvant
      intravenous (IV) and IP chemotherapy with paclitaxel and a platinum-based agent
      were eligible. Age, performance status, tumor origin, stage, and grade were
      recorded. First recurrences were identified using CA125 values, radiographic
      studies, operative notes, and pathology reports. Sites of recurrence were
      classified as intraperitoneal (IP), extraperitoneal (EP) or distant. Kaplan-Meier
      estimates and Cox multivariate regression models were used to assess the
      associations between recurrent disease distribution and progression-free survival
      (PFS) and overall survival (OS). RESULTS: One hundred forty-three patients met
      the criteria for inclusion. The majority were Stage III (86%) and serous
      histology (77%). Eighty-four (58.7%) received IV/IP paclitaxel/cisplatin per GOG
      172 and 59 (41.3%) received IV/IP paclitaxel/carboplatin. Seventy-two percent
      completed 6 cycles. Ninety (62.9%) patients manifested a recurrence. One-hundred
      twelve sites of recurrence were identified with 70 (62.5%) IP and 42 (37.5%) EP
      and distant sites. Nineteen (21%) recurred in more than one site, i.e. both IP
      and EP locations. Site of recurrence did not impact OS, however, patients who
      recurred in multiples sites had significantly worse OS (p<0.001). CONCLUSION:
      Approximately 40% of patients treated with IP chemotherapy have a first
      recurrence outside the peritoneal cavity. Though site of recurrence did not
      affect OS those with multi-focal recurrence demonstrate worse survival.

PMID- 22659194
TI  - Observations on the therapeutic practices of riverine communities of the Unini
      River, AM, Brazil.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Parts and products of animals and plants, like
      exudates, have been used for medicinal and/or toxic purposes by various human
      groups throughout history. However, few ethnopharmacological studies have engaged
      their rescue. AIM OF THE STUDY: To perform a broad ethnopharmacological survey of
      the local medicine practiced by traditional healing experts living in relative
      isolation at seven communities within the Amazon rainforest, in order to provide
      the basis for further pharmacological studies of the most promising findings.
      MATERIALS AND METHODS: The field work was conducted using an ethnographic
      approach with the assistance of a doctor. Plants and animals, as well as their
      products and derivatives, reported by the practitioners as being involved in
      healing practices were collected, identified and deposited in scientific
      collections. RESULTS: A total of 33 traditional healing experts were selected and
      interviewed; they described themselves as: healer, midwife, knowledgeable of
      natural drugs or 'desmintidor' (an expert in massage techniques for the treatment
      of muscle contractures and joint sprains). In this therapeutic practice, 122
      plant species, belonging to 60 botanical families, were indicated and collected;
      the most frequently mentioned families were: Fabaceae s.l. (10%), Arecaceae (6%),
      Zingiberaceae (5%) and Lamiaceae (5%). Plant exudates from 14 of those plant
      species were also indicated and collected, with those from the Burseraceae family
      being the most common. Furthermore, 57 animals belonging to 35 taxonomic families
      were indicated. They most frequently belonged to 2 families of bony fishes:
      Cichlidae (14%) and Characidae (9%). Plants and animals were indicated for 67
      therapeutic uses and grouped into 21 usage categories; the psychoactive category
      was associated with the greatest number of used resources (17%), followed by the
      cultural syndromes category (16.7%). CONCLUSIONS: The geographic isolation and
      limited access to medical care in these communities resulted in unique, rich and
      consistent therapeutic system. There was a high degree of agreement among
      interviewees regarding the use of the same resources especially in the
      categories: psychoactive, cultural syndromes, pregnancy and childbirth, and
      inflammatory processes, suggesting a high degree of repetition and
      intercommunication. Further pharmacological and phytochemical investigations may
      search for new bioactive compounds among the described resources.

PMID- 22659195
TI  - Antiplasmodial activity of the andiroba (Carapa guianensis Aubl., Meliaceae) oil
      and its limonoid-rich fraction.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: From seeds of Carapa guianensis the Amazon native
      people extracts the andiroba oil, which is traditionally used as febrifuge, anti
      malarial, insecticidal and repellant. The non-saponifiable fraction separated
      from the oil is rich in limonoids, which assigns its pharmacological effects.
      MATERIALS AND METHODS: The andiroba oil and its limonoid-rich fraction were
      submitted to in vitro antiplasmodial bioassay using W(2) and Dd(2) strains of
      Plasmodium falciparum. The acute toxicity of andiroba oil was evaluated. The
      limonoid-rich fraction was subjected to fractionation and identified its major
      constituents. RESULTS: Andiroba oil and its limonoid-rich fraction inhibited the
      growth of W(2) clone in 100%, between 24 and 72 h, at concentrations of 8.2
      MUg/mL and 3.1 MUg/mL, respectively. Under the same conditions, the parasitaemia
      of Dd(2) clone provoked by the andiroba oil showed inhibition of 31% (IC(50) >82
      MUg/mL) with a time-dependent relationship of 24h and inhibition of 88% (IC(50)
      8.4 MUg/mL) after 72 h, while for the limonoid-rich fraction the inhibition of
      Dd(2) clone was 56% (IC(50) 2.8MUg/mL) at 24h and 82% (IC(50) 0.4 MUg/mL) after
      72 h. Andiroba oil in acute toxicity test with a fixed dose (LD(50) >2000 mg/kg)
      was not toxic The limonoids identified in the oil were gedunin, 6alpha
      acetoxygedunin, 7-deacetoxy-7-oxogedunin, 7-deacetylgedunin, 1,2-dihydro-3beta
      hydroxy-7-deacetoxy-7-oxogedunin and andirobin. Gedunin and derivatives has been
      reputed as anti-malarials. CONCLUSION: The results support the traditional use of
      andiroba oil as antiplasmodial, which additionally proved not to be toxic in
      bioassays conducted with mice.

PMID- 22659196
TI  - Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: N-Alkylamides (NAAs) are a promising group of
      bioactive compounds, which are anticipated to act as important lead compounds for
      plant protection and biocidal products, functional food, cosmeceuticals and drugs
      in the next decennia. These molecules, currently found in more than 25 plant
      families and with a wide structural diversity, exert a variety of biological
      pharmacological effects and are of high ethnopharmacological importance. However,
      information is scattered in literature, with different, often unstandardized,
      pharmacological methodologies being used. Therefore, a comprehensive NAA database
      (acronym: Alkamid) was constructed to collect the available structural and
      functional NAA data, linked to their occurrence in plants (family, tribe,
      species, genus). MATERIALS AND METHODS: For loading information in the database,
      literature data was gathered over the period 1950-2010, by using several search
      engines. In order to represent the collected information about NAAs, the plants
      in which they occur and the functionalities for which they have been examined, a
      relational database is constructed and implemented on a MySQL back-end. RESULTS:
      The database is supported by describing the NAA plant-, functional- and chemical
      space. The chemical space includes a NAA classification, according to their fatty
      acid and amine structures. CONCLUSIONS: The Alkamid database (publicly available
      on the website http://alkamid.ugent.be/) is not only a central information point,
      but can also function as a useful tool to prioritize the NAA choice in the
      evaluation of their functionality, to perform data mining leading to quantitative
      structure-property relationships (QSPRs), functionality comparisons, clustering,
      plant biochemistry and taxonomic evaluations.

PMID- 22659197
TI  - Left ventricular outflow tract to left atrium fistula due to non-valve Listeria
      monocytogenes endocarditis.

PMID- 22659198
TI  - Angiotensin-converting enzyme inhibitors: first-line agents in cardiovascular
      protection?

PMID- 22659200
TI  - Personalized medicine: hope or hype.

PMID- 22659202
TI  - Poecilogony and population genetic structure in Elysia pusilla (Heterobranchia:
      Sacoglossa), and reproductive data for five sacoglossans that express dimorphisms
      in larval development.
AB  - Credible cases of poecilogony, the production of two distinct larval morphs
      within a species, are extremely rare in marine invertebrates, yet peculiarly
      common in a clade of herbivorous sea slugs, the Sacoglossa. Only five animal
      species have been reported to express dimorphic egg sizes that result in
      planktotrophic and lecithotrophic larvae: the spionid polychaete Streblospio
      benedicti and four sacoglossans distributed in temperate estuaries or the
      Caribbean. Here, we present developmental and genetic evidence for a fifth case
      of poecilogony via egg-size dimorphism in the Sacoglossa and the first example
      from the tropical Indo-Pacific. The sea slug Elysia pusilla produced both
      planktotrophic and lecithotrophic larvae in Guam and Japan. Levels of genetic
      divergence within populations were markedly low and rule out cryptic species.
      However, divergence among populations was exceptionally high (10-12% at the
      mitochondrial cytochrome c oxidase I locus), illustrating that extensive
      phylogeographic structure can persist in spite of the dispersal potential of
      planktotrophic larvae. We review reproductive, developmental, and ecological data
      for the five known cases of poecilogony in the Sacoglossa, including new data for
      Costasiella ocellifera from the Caribbean. We hypothesize that sacoglossans
      achieve lecithotrophy at smaller egg sizes than do related clades of marine
      heterobranchs, which may facilitate developmental plasticity that is otherwise
      vanishingly rare among animals. Insight into the environmental drivers and
      evolutionary results of shifts in larval type will continue to be gleaned from
      population-level studies of poecilogonous taxa like E. pusilla, and should inform
      life-history theory about the causes and consequences of alternative development
      modes in marine animals.

PMID- 22659201
TI  - Preliminary insights into the phylogeography of the yellow-bellied sea snake,
      Pelamis platurus.
AB  - The yellow-bellied sea snake, Pelamis platurus (Elapidae, Hydrophiinae), has the
      largest distribution of any snake species, and patterns related to its
      distribution and regional color variation suggest there is population structuring
      in this species. Here, we use mitochondrial (ND4, Cyt-b) and nuclear (RAG-1) DNA
      to (1) test whether genetic variation is associated with local variation in color
      pattern, and (2) assess whether large-scale patterns of genetic variation are
      correlated with geographic distribution across the Pacific Ocean. We found low
      levels of genetic variation and shallow population structure that are correlated
      with local variation in color pattern and with geographic distribution. The low
      levels of genetic divergence indicate a relatively high rate of gene flow
      throughout the Pacific region and/or a recent expansion of range, both of which
      could be attributable to the passive drifting of these snakes on oceanic surface
      currents. The mtDNA data conform closely to a model of past exponential
      population growth, and this may have been associated with the species' large
      eastward and westward expansion of range. The pattern of low nucleotide and high
      haplotype diversity suggests that this population growth occurred in the
      relatively recent past. Data from drifting buoys can potentially act as
      informative models for predicting patterns of drifting in Pelamis and for
      generating additional testable hypotheses relating to its population structure
      and biogeography. Future studies should employ nuclear microsatellite markers to
      investigate population structure in this species at a finer scale. The
      exploitation of oceanic currents as a novel and highly efficient dispersal
      mechanism has likely facilitated gene flow throughout the Pacific Ocean in this
      uniquely pelagic species of sea snake, resulting in a distribution spanning over
      half of the earth's circumference.

PMID- 22659203
TI  - Patterns of nuclear genetic variation in the poecilogonous polychaete Streblospio
      benedicti.
AB  - The evolution of marine larvae is replete with transitions in trophic mode, but
      little is known about how, at the genetic level, these transitions are achieved.
      Basic parameters, including the number of underlying loci, their molecular
      characteristics, and the population-genetic processes that drive transitions
      remain unknown. Streblospio benedicti, an abundant benthic polychaete with
      heritable poecilogony, provides a unique genetically tractable system for
      addressing these issues. Individuals of S. benedicti vary in diverse aspects of
      development. Some females produce small, planktotrophic larvae, whereas others
      produce large, yolky larvae capable of settling without feeding. Here, I present
      estimates of basic features of nuclear genetic variation in S. benedicti to lay
      the foundations for subsequent efforts to understand the genetic basis of
      poecilogony. Sequence of ~20 kb of random nuclear DNA indicates that the
      nucleotide composition, at 62.1% A + T, is typical of lophotrochozoan genomes.
      Population-genetic data, acquired by sequencing two loci (~2500 bp) in multiple
      animals of each developmental morph, indicate that the morphs exhibit very little
      differentiation at random loci. Nucleotide heterozygosity (thetapi) is ~0.5-1%
      per site, and linkage disequilibrium decays within a few kilobases (rho  ~ 3 *
      10(-3) per site). These data suggest that genetic mapping by association will
      require a high density of markers, but linkage mapping and identification of
      regions of elevated inter-morph differentiation hold great promise.

PMID- 22659199
TI  - Personalized medicine: hope or hype?
AB  - Medicine has always been personalized. For years, physicians have incorporated
      environmental, behavioural, and genetic factors that affect disease and drug
      response into patient management decisions. However, until recently, the
      'genetic' data took the form of family history and self-reported race/ethnicity.
      As genome sequencing declines in cost, the availability of specific genomic
      information will no longer be limiting. Rather, our ability to parse these data
      and our decision whether to use it will become primary. As our understanding of
      genetic association with drug responses and diseases continues to improve,
      clinically useful genetic tests may emerge to improve upon our previous methods
      of assessing genetic risks. Indeed, genetic tests for monogenic disorders have
      already proven useful. Such changes may usher in a new era of personalized
      medicine. In this review, we will discuss the utility and limitations of personal
      genomic data in three domains: pharmacogenomics, assessment of genetic
      predispositions for common diseases, and identification of rare disease-causing
      genetic variants.

PMID- 22659204
TI  - Paratransgenesis: an approach to improve colony health and molecular insight in
      honey bees (Apis mellifera)?
AB  - The honey bee (Apis mellifera) is highly valued as a commercial crop pollinator
      and a model animal in research. Over the past several years, governments,
      beekeepers, and the general public in the United States and Europe have become
      concerned by increased losses of honey bee colonies, calling for more research on
      how to keep colonies healthy while still employing them extensively in
      agriculture. The honey bee, like virtually all multicellular organisms, has a
      mutually beneficial relationship with specific microbes. The microbiota of the
      gut can contribute essential nutrients and vitamins and prevent colonization by
      non-indigenous and potentially harmful species. The gut microbiota is also of
      interest as a resource for paratransgenesis; a Trojan horse strategy based on
      genetically modified symbiotic microbes that express effector molecules
      antagonizing development or transmission of pathogens. Paratransgenesis was
      originally engineered to combat human diseases and agricultural pests that are
      vectored by insects. We suggest an alternative use, as a method to promote health
      of honey bees and to expand the molecular toolbox for research on this beneficial
      social insect. The honey bees' gut microbiota contains lactic acid bacteria
      including the genus Lactobacillus that has paratransgenic potential. We present a
      strategy for transforming one Lactobacillus species, L. kunkeei, for use as a
      vector to promote health of honey bees and functional genetic research.

PMID- 22659205
TI  - beta-cyclodextrin-cobalt ferrite nanocomposite as enhanced sensing platform for
      catechol determination.
AB  - An electrochemical sensor based on beta-cyclodextrin-cobalt ferrite nanocomposite
      was developed for the sensitive detection of catechol (CT). To construct the base
      of the sensor, a novel composite was initially fabricated and used as the
      substrate material by combining cobalt ferrite nanocomposite and beta
      cyclodextrin via a simple sonication-induced assembly. Due to the high catechol
      loading capacity on the electrode surface and the upstanding electric
      conductivity of cobalt ferrite nanocomposite, the electrochemical response of the
      fabricated sensor was greatly enhanced and displayed excellent analytical
      performance for catechol detection from 1 to 200 MUM with a low detection limit
      of 0.12 MUM (S/N=3). Moreover, the developed electrochemical sensor exhibited
      good selectivity and acceptable reproducibility and could be used for the
      detection of catechol in water samples.

PMID- 22659206
TI  - Electrical properties of polycrystalline GaN films functionalized with cysteine
      and stabilization of GaN nanoparticles in aqueous media.
AB  - GaN was synthesized onto sapphire substrates by chemical vapor deposition,
      reacting gallium, ammonium chloride and ammonia. The polycrystalline films were
      immersed in glycine, aspartic acid and cysteine solutions. Cysteine chemisorbed
      onto GaN films produced detectable changes in conductivity, mobility and Hall
      coefficient indicating that GaN is capable of detecting and reacting with
      thiolate groups, which was confirmed by X-ray photoelectron spectroscopy. The Cys
      GaN film solution was adjusted to pH 10, upon which the GaN nanoparticles were
      transferred to the aqueous phase forming a suspension stable for seven days. The
      alkaline colloid was then further adjusted down to pH 3 retaining stability for
      three days. The GaN colloid obtained represents a suitable medium to study GaN
      properties for biological applications.

PMID- 22659207
TI  - Electrochemical studies of quinine in surfactant media using hanging mercury drop
      electrode: a cyclic voltammetric study.
AB  - The electrochemical behavior of quinine was investigated by cyclic voltammetry
      (CV) and square wave voltammetry (SWV) using surfactant. The reduction peak
      current of quinine increases remarkably in presence of 1% CTAB. Its
      electrochemical behavior is quasi-reversible in the Britton-Robinson buffers of
      pH 10.38 by exhibiting the well-defined single cathodic and anodic waves and the
      ratio of I(p)(a)/I(p)(c) approaching one at the scan rate of 500 mVs(-1). On the
      basis of CV, SWV and Coulometry, electrochemical reduction mechanism of quinine
      has been proposed which has shown that protonation occurs on the nitrogen of the
      quinoline moiety. Linearity was obtained when the peak currents (I(p)) were
      plotted against concentrations of quinine in the range of 30.0-230.0 ng mL(-1)
      with a detection limit of 0.132 ng mL(-1) in SWV and 90.0-630.0 ng mL(-1) with a
      detection limit of 0.238 ng mL(-1) in DPV. Fast and sensitive SWV has been
      applied for the quantitative analysis of quinine in bark of Cinchona sp. and in
      soft drinks and a good recovery was obtained. The accuracy and precision of the
      method are determined and validated statistically. No interferences from other
      food additives were observed. The relative standard deviation for intraday and
      interday assay was 0.89 and 0.73% (n=3) respectively.

PMID- 22659208
TI  - Characterization and side effect analysis of a newly designed nanoemulsion
      targeting human serum albumin for drug delivery.
AB  - Human serum albumin (HSA), the most abundant protein in plasma, plays an
      important role in the transportation of metabolic and exogenous compounds,
      particularly drugs. However, it takes a carrier to bring the metabolite or
      compound to the plasma for subsequent transportation in blood using HSA. A
      nanoemulsion which constitutes a mixture of two immiscible liquid phases can act
      as an effective drug carrier due to its unique properties. In this study, we
      report the characterization results of a newly designed nanoemulsion via dynamic
      light scattering (DLS) and scanning electron microscopy (SEM), followed by
      results on the alterations in the structure of HSA upon interaction with the
      nanoemulsion using circular dichroism (CD) as well as intrinsic and extrinsic
      fluorescence spectroscopy methods at ambient and physiological temperatures.
      Results of SEM and DLS show that particles making up the nanoemulsion have a
      nearly monodisperse size distribution and spherical morphology. Results of
      intrinsic fluorescence spectroscopy show decreasing emission intensity with
      increasing nanoemulsion concentration. Results from this study using 1-anilino-8
      naphthalene sulfonic acid (ANS) confirm the intrinsic fluorescence data and
      reveal that adding the nanoemulsion to HSA leads to an increase in fluorescence
      intensity. These results imply that the interaction between the nanoemulsion and
      HSA cause a structural transformation in which native HSA turns "inside out" to
      expose its hydrophobic core to the surrounding environment. Far-UV-CD results
      indicate that the nanoemulsion induces a loss in alpha-helical structure of the
      HSA protein. In summary, the exposure of the blood carrier protein HSA to a newly
      designed nanoemulsion resulted in significant alterations of protein structure
      and conformation depicted by a red shift in maximum fluorescence intensity,
      decreased alpha-helical structure, and increased exposure of nonpolar or
      accessible hydrophobic surface of HSA to the solvent.

PMID- 22659209
TI  - Functional ionic liquids induced the formation of mitochondria targeted
      fluorescent core-shell ellipsoidal nanoparticles with anticancer properties.
AB  - A functional ionic liquid (IL) (IL=4-acetyl-N-butyl pyridinium
      hexafluorophosphate) was synthesized and conjugated with low toxicity of
      nanospheres (RBITC@SiO(2)), forming a new kind of fluorescent core-shell
      ellipsoidal RBITC@SiO(2)-IL nanoparticle. In vitro assay results indicate that
      particle shape plays an important role in cellular interactions with NPs.
      Furthermore, the positively charged ellipsoidal RBITC@SiO(2)-IL nanoparticles can
      enter into HeLa cells and induce the cells to condense, split and decrease on the
      oxygen consumption. The enhanced cell image and decrease of mitochondria
      potential indicate that the ellipsoidal RBITC@SiO(2)-IL nanoparticles could be
      uptaken by HeLa cells through mitochondria involved path. Experimental results
      give us a new path to design nano-medicines through ionic liquid modified silica
      nanoparticles to target mitochondria.

PMID- 22659210
TI  - Modulation of release of paclitaxel from composite cerasomes.
AB  - Efforts to improve the stability of liposomes have recently led to the
      development of organic-inorganic liposomal cerasomes. In this study, we explore
      the potential to modulate the sustained release of paclitaxel from cerasomes by
      alteration in vesicle composition. Specifically, composite cerasomes have been
      prepared from mixtures of cerasome-forming lipid (lipid 1) and 1,2-distearoyl-sn
      glycero-3-phosphocholine (lipid 2) via one-step construction. The influences of
      vesicle composition on the physical properties (e.g., particle diameter and
      surface charge density), physiochemical and long-term storage stability, drug
      loading capacity, and release rates of paclitaxel have been investigated.
      Notably, a wide range of the release profiles of paclitaxel have been achieved by
      varying the contents of lipid 2, and the composite vesicles display excellent
      stability when the percentage content of lipid 2 is lower than 50%. Composite
      vesicles composed of lipids 1 and 2 at a 1:1 molar ratio also exhibited good
      cytocompatibility and the released paclitaxel effectively inhibit the
      proliferation of HeLa cancer cells. Together, the development of composite
      vesicles offers a promising strategy to obtain excellent stability, good drug
      loading capacity and cytocompatibility, and enhanced paclitaxel release in single
      vesicles.

PMID- 22659211
TI  - The importance of ether-phospholipids: a view from the perspective of mouse
      models.
AB  - Ether-phospholipids represent an important group of phospholipids characterized
      by an alkyl or an alkenyl bond at the sn-1 position of the glycerol backbone.
      Plasmalogens are the most abundant form of alkenyl-glycerophospholipids, and
      their synthesis requires functional peroxisomes. Defects in the biosynthesis of
      plasmalogens are the biochemical hallmark of the human peroxisomal disorder
      Rhizomelic Chondrodysplasia Punctata (RCDP), which is characterized by defects in
      eye, bone and nervous tissue. The generation and characterization of mouse models
      with defects in plasmalogen levels have significantly advanced our understanding
      of the role and importance of plasmalogens as well as pathogenetic mechanisms
      underlying RCDP. A review of the current mouse models and the description of the
      combined knowledge gathered from the histopathological and biochemical studies is
      presented and discussed. Further characterization of the role and functions of
      plasmalogens will contribute to the elucidation of disease pathogenesis in
      peroxisomal and non-peroxisomal disorders. This article is part of a Special
      Issue entitled: Metabolic Functions and Biogenesis of Peroxisomes in Health and
      Disease.

PMID- 22659212
TI  - Trials and tribulations of stimulating human cardiac ganglia for autonomic
      intervention.

PMID- 22659213
TI  - Hemoglobin spectroscopy to evaluate hemodynamic function during tachycardias: the
      future of ICD discrimination algorithms?

PMID- 22659214
TI  - Materialization of ghosts: severe intracardiac masses after pacemaker lead
      extraction requiring immediate surgical intervention.

PMID- 22659215
TI  - Cryocatheter as a tool for retrieving endovascular foreign bodies.

PMID- 22659216
TI  - Very small photoluminescent gold nanoparticles for multimodality biomedical
      imaging.
AB  - An original synthesis method based on X-ray irradiation produced gold
      nanoparticles (AuNPs) with two important properties for biomedical research:
      intense visible photoluminescence and very high accumulation in cancer cells. The
      nanoparticles, coated with MUA (11-mercaptoundecanoid acid), are very small (1.4
      nm diameter); the above two properties are not present for even slightly larger
      sizes. The small MUA-AuNPs are non-cytotoxic (except for very high
      concentrations) and do not interfere with cancer cell proliferation.
      Multimodality imaging using visible light fluorescence and X-ray microscopy is
      demonstrated by tracing the nanoparticle-loaded tumor cells.

PMID- 22659218
TI  - Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic
      hepatitis B who stop long-term treatment with adefovir.
AB  - BACKGROUND & AIMS: Little is known about the biochemical and virological effects
      of stopping long-term nucleos(t)ide analogue therapy for hepatitis B e antigen
      (HBeAg)-negative patients with chronic hepatitis B (CHB). METHODS: We performed a
      cohort observational study, following 33 HBeAg-negative patients with CHB,
      undetectable serum HBV DNA, and normal levels of aminotransferases after long
      term (4 or 5 years) treatment with adefovir dipivoxil (ADV). All patients were
      followed for 5.5 years; follow-up visits included measurements of serum alanine
      aminotransferase (ALT), hepatitis B surface antigen (HBsAg), and HBV DNA monthly
      for the first 6 months and every 3-6 months thereafter. Various factors were
      measured at baseline, the end of treatment (EOT), and following treatment to
      identify those associated with clearance of HBsAg. RESULTS: During the first few
      months of the postdiscontinuation period, all patients experienced virological
      and 25 (76%) had biochemical relapse. During the follow-up period, 18 patients
      (55%) who had discontinued antiviral therapy achieved sustained response (HBV DNA
      level <2000 IU/L, persistently normal level of ALT). Among these, 13 (72%)
      cleared HBsAg. Fifteen patients (45%) with virological and/or biochemical relapse
      were re-treated with oral antiviral agents (11 during the first 18 months and 4
      after the third year), without evidence of liver decompensation; only 1 lost
      HBsAg (6%). Higher pretreatment and EOT levels of ALT, no previous treatment with
      interferon, and lower level of HBsAg at the EOT were significantly associated
      with HBsAg clearance based on multivariate analysis. CONCLUSIONS: In HBeAg
      negative patients with CHB, it is safe and effective to discontinue ADV therapy
      after 4 or 5 years; 55% of patients have sustained responses, and 39% of patients
      lose HBsAg.

PMID- 22659217
TI  - Cellular and molecular determinants for the development of natural and induced
      regulatory T cells.
AB  - Regulation of immune responses to self and foreign antigens is critically
      dependent on suppressive CD4(+) T cells characterized by expression of Foxp3. The
      large majority of regulatory T (Treg) cells develop in the thymus as a stable
      suppressive lineage. However, under the proper physiological conditions,
      conventional peripheral CD4(+) T lymphocytes also develop into Treg cells,
      particularly in the gut mucosa and inflammatory tissue sites. This review will
      focus on our current understanding of the immunological and molecular signals
      controlling the development of thymic derived natural (n)Treg and peripheral
      converted induced (i)Treg cells. Given the importance of Foxp3 in the development
      of these cells, particular attention is placed on how such signals are integrated
      to induce and maintain the expression of this signature transcriptional regulator
      of Treg cells.

PMID- 22659219
TI  - Phosphoprotein abundance changes in hypertensive cardiac remodeling.
AB  - There is over-whelming evidence that protein phosphorylations regulate cardiac
      function and remodeling. A wide variety of protein kinases, e.g.,
      phosphoinositide 3-kinase (PI3K), Akt, GSK-3, TGFbeta, and PKA, MAPKs, PKC, Erks,
      and Jaks, as well as phosphatases, e.g., phosphatase I (PP1) and calcineurin,
      control cardiomyocyte growth and contractility. In the present work, we used
      global phosphoprotein profiling to identify phosphorylated proteins associated
      with pressure overload (PO) cardiac hypertrophy and heart failure.
      Phosphoproteins from hypertrophic and systolic failing hearts from male
      hypertensive Dahl salt-sensitive rats, trans-aortic banded (TAC), and
      spontaneously hypertensive heart failure (SHHF) rats were analyzed. Profiling was
      performed by 2-dimensional difference in gel electrophoresis (2D-DIGE) on phospho
      enriched proteins. A total of 25 common phosphoproteins with differences in
      abundance in (1) the 3 hypertrophic and/or (2) the 2 systolic failure heart
      models were identified (CI>99%) by matrix assisted laser desorption ionization
      mass spectrometry (MALDI-MS) and Mascot analysis. Among these were (1)
      myofilament proteins, including alpha-tropomyosin and myosin regulatory light
      chain 2, cap Z interacting protein (cap ZIP), and tubulin beta5; (2)
      mitochondrial proteins, including pyruvate dehydrogenase alpha, branch chain
      ketoacid dehydrogenase E1, and mitochondrial creatine kinase; (3) phosphatases,
      including protein phosphatase 2A and protein phosphatase 1 regulatory subunit;
      and (4) other proteins including proteosome subunits alpha type 3 and beta type
      7, and eukaryotic translation initiation factor 1A (eIF1A). The results include
      previously described and novel phosphoproteins in cardiac hypertrophy and
      systolic failure.

PMID- 22659220
TI  - Differential relationships between sub-traits of BIS-11 impulsivity and executive
      processes: an ERP study.
AB  - There is mixed evidence for a relationship between impulsivity and executive
      functions. Although impulsivity is heterogeneous, previous research did not
      examine partial relationships controlling for shared variance across sub-traits
      to evaluate the specificity of these associations. Eighty-five undergraduates
      completed the Barratt Impulsiveness Scale-11 (BIS-11) and the AX-expectancy
      version of the Continuous Performance Task (AX-CPT). This task engenders a
      conflict between two response tendencies by manipulating the frequency of
      specific trial types. We conducted mixed model analyses to determine the unique
      variance in behavioral and electrophysiological indices of relevant cognitive
      functions accounted for by the facets of BIS-11. Motor Impulsiveness was
      associated with smaller P3 across sites and conditions suggesting a general
      cognitive limitation not specific to the condition requiring the most inhibition,
      and larger N2 in some conditions indicating heightened conflict detection. Non
      Planning Impulsiveness was related to smaller N2 when inhibiting a primed
      response and with greater P3 in some contexts. Attentional Impulsiveness appeared
      to be associated with an inefficient conflict detection system indicated by
      relatively normal engagement in trials involving the non-potent response, but
      relatively over engagement in the prepotent condition. Our findings suggest that
      sub-traits of impulsivity are differentially related to executive processes.

PMID- 22659221
TI  - Sex moderates the relationship between worry and performance monitoring brain
      activity in undergraduates.
AB  - Research suggests that abnormal performance-monitoring contributes to the
      etiology and maintenance of anxious pathology. Moreover, the anxiety-performance
      monitoring relationship appears to be specific to the worry dimension of anxiety.
      Given that anxiety (and worry in particular) is twice as prevalent in women as
      men, and most studies to date have employed small samples which are underpowered
      to detect sex-differences, it is possible that sex may be an important moderator
      of the worry-performance-monitoring relationship. No studies have directly
      compared the worry-performance-monitoring relationship between men and women,
      however. In the current study, we extended our recent work showing a unique
      relationship between worry and performance monitoring brain potentials in female
      undergraduates by comparing this relationship to that between worry and
      performance-monitoring brain potentials in male participants. Seventy-nine female
      and 70 male undergraduates from an ongoing study of anxiety and performance
      monitoring performed a letter-flanker task while their brain activity was
      recorded. Results revealed that worry was associated with exaggerated performance
      monitoring, as indexed by increased error-related negativity/correct-response
      negativity, in female, but not male undergraduates. These findings suggest that
      the functional relationship between worry and performance-monitoring is sex
      specific and have implications for understanding the role of performance
      monitoring in the development and maintenance of anxiety. Specifically, linking
      the worry-performance-monitoring relationship to other female-specific
      biopsychosocial factors represents an important direction for future research.

PMID- 22659222
TI  - Local application of gentamicin-containing collagen implant in the prophylaxis
      and treatment of surgical site infection following vascular surgery.
AB  - BACKGROUND: The development of surgical site infection (SSI) following vascular
      surgery is an important issue for healthcare providers as it has serious
      implications for both patient morbidity and mortality. METHODS: Five publications
      were identified using the PubMed online database and search terms 'gentamicin
      containing collagen implant' plus 'surgical site infection', 'wound infection'
      and 'vascular surgery'. RESULTS: The reviewed publications demonstrated that
      prophylactic use of GCCI in conjunction with standard treatment reduces the SSI
      rate in patients operated on for femeropopliteal bypass grafting. The
      prophylactic use of GCCI may also have a role to play in patients at high-risk of
      infection (e.g. in those with co-morbidities such as obesity) and in high-risk
      procedures (e.g. surgical revision to correct anastomotic aneurysm or
      dehiscence). GCCI in conjunction with systemic antibiotics may also be effective
      in the treatment of wound infections of the groin following vascular
      reconstruction. CONCLUSION: This review demonstrates that GCCI have a role to
      play in preventing and treating SSI following vascular reconstruction when used
      in conjunction with standard treatment approaches. Additional randomised,
      controlled studies are required to further establish the efficacy and cost
      effectiveness of GCCI in vascular surgery.

PMID- 22659223
TI  - Impact of soaking gentamicin-containing collagen implants on potential
      antimicrobial efficacy.
AB  - BACKGROUND: The purpose of this study is to evaluate how wetting of Collatamp (a
      gentamicin-containing collagen implant [GCCI]) impacts on the gentamicin content
      of the implant and whether this affects its potential antibacterial efficacy.
      METHODS: GCCI (Collatamp((r)), EUSA Pharma [Europe], Oxford, United Kingdom)
      containing 130 mg gentamicin and 280 mg collagen (10 cm * 10 cm) were immersed in
      300 mL normal saline for up to 6h. At set times after immersion the GCCI were
      removed, the saline diluted in normal human serum and the gentamicin content
      assayed by a validated immunoassay (Cedia, Microgenics Ltd, UK) to provide an
      estimate of the loss from each implant. The mean concentration data were then
      fitted to an exponential decay model (WinNonLin, Pharsight, US). RESULTS: After a
      very short immersion period there was significant loss of gentamicin from the
      implants with a mean loss of 6.7% at 2 s, increasing to 40.5% at 1 min and
      essentially total loss by 6 h of immersion. Loss of gentamicin followed a complex
      elution profile, with elution half-lives ranging from 50 s on initial immersion
      to 99 min late in the elution period. CONCLUSION: This study provides clear
      evidence that even a short period of dipping of Collatamp implants, and probably
      other GCCI, before insertion into the patient results in a significant loss of
      gentamicin which may be of clinical significance unless the period of soaking is
      very short. We therefore recommend that wetting of these implants before
      insertion is not undertaken.

PMID- 22659224
TI  - Local application of gentamicin-containing collagen implant in the prophylaxis of
      surgical site infection following gastrointestinal surgery.
AB  - BACKGROUND: Gastrointestinal surgery is associated with one of the highest rates
      of SSI due to the nature of the surgery and to the added complication of
      operating on patients with significant co-morbidities. This high rate of SSI may
      negatively impact wound healing, patient recovery time, length of hospital stay
      and associated healthcare costs. This article provides an overview of the
      efficacy and safety of prophylactic application of resorbable gentamicin
      containing collagen implants (GCCI) in the prevention of SSI following GI
      surgical procedures. METHOD: Thirteen publications were identified using the
      PubMed online database and search terms 'gentamicin collagen implant' plus
      'surgical site infection', 'wound infection' and 'gastrointestinal surgery'.
      RESULTS: Eleven out of 13 studies have demonstrated that prophylactic use of GCCI
      can reduce the wound infection rate in high-risk GI surgical procedures (e.g.
      abdominoperineal resection [APR]) and improve wound healing after pilonidal sinus
      excision. GCCI may also have a role to play in preventing anastomotic leakage
      following mesorectal excision for rectal carcinoma. It is recommended that GCCI
      are used dry in line with the manufacturer's recommendations. CONCLUSION: This
      review demonstrates that GCCI can significantly reduce surgical site infection
      following GI surgery including pilonidal sinus excision and high-risk procedures
      such as APR.

PMID- 22659225
TI  - Children's perceptions of physical activity environments captured through
      ecological momentary assessment: a validation study.
AB  - OBJECTIVE: This study used ecological momentary assessment (EMA) to investigate
      whether children's perceptions of physical activity (PA) settings correspond with
      (1) parents' perceptions of neighborhood characteristics (convergent construct
      validity) and (2) children's level of PA in those settings (concurrent criterion
      validity). METHODS: Low-to-middle income, ethnically-diverse children (N=108)
      (ages 9-13) living in Southern California participated in 8 days of EMA during
      non-school time. EMA measured current activity type (e.g., sports/exercise, TV
      watching) and perceptions of the current setting (i.e., vegetation, traffic,
      safety). The Neighborhood Environment Walkability Survey (NEWS) assessed parents'
      perceptions of neighborhood characteristics. EMA responses were time-matched to
      moderate-to-vigorous physical activity (MVPA) (measured by accelerometer) in the
      30 min before and after each EMA survey. Data were collected in 2009-2010.
      RESULTS: Children's perceptions of vegetation and traffic in PA settings
      corresponded with parents' perceptions of the aesthetics (OR=2.21, 95% CI=1.04
      4.73) and traffic (OR=2.64, 95% CI=1.31-5.30) in neighborhood environment,
      respectively. MVPA minutes were higher in settings perceived by children to have
      less traffic (beta=3.47, p<.05). CONCLUSIONS: This work provides initial support
      for the construct and criterion validity of EMA-based measures of children's
      perceptions of their PA environments.

PMID- 22659226
TI  - Using colorectal trends in the U.S. to identify unmet primary care needs of
      vulnerable populations.
AB  - BACKGROUND: Colorectal cancer screening (CRC) disparities have worsened in recent
      years. OBJECTIVE: To examine progress toward Healthy People 2010 goals for CRC
      screening among ethnic/racial groups, including disaggregated Latino groups.
      METHODS: Multivariate logistic regressions examined associations between
      ethnicity/race and primary outcomes of self-reported guideline-concordant CRC
      screenings considering time trends for 65,947 respondents of the Medical
      Expenditure Panel Survey from 2000 to 2007 age 50-years and older from six groups
      (non-Latino White, non-Latino Black, Puerto Rican, Cuban, Mexican, and Other
      Latino). We also tested for modification effects by education, income, and health
      insurance. RESULTS: Most groups approached Healthy People 2010 CRC screening rate
      goals, including non-Latino Whites (47%), non-Latino Blacks (42%) and Puerto
      Ricans (40%), while Mexicans remained disparately lower (28%). Higher education,
      income and insurance coverage, partially attenuated this lower likelihood, but
      Mexican rates remained significantly lower than non-Latino Whites for receiving
      endoscopy in the past 5 years {OR(95% CI)=0.68(0.59-0.77)} and having received
      any CRC screening {0.70(0.62-0.79)}. CONCLUSIONS: Among ethnic/racial groups
      examined, only Mexicans met healthcare disparity criteria in CRC screening.
      Findings suggest that healthcare equity goals can be attained if resources
      affecting continuity of care or ability to pay for preventive services are
      available, and targeted populations are adequately identified.

PMID- 22659228
TI  - Multiple Cryptosporidium genotypes detected in wild black rats (Rattus rattus)
      from northern Australia.
AB  - As part of a broader investigation into the potential role of black rats (Rattus
      rattus) as disease vectors into native small mammal populations of northern
      Australia, blood and faecal samples from wild black rats were screened by
      molecular methods, for piroplasms (Babesia and Theileria), trypanosomes and the
      enteric parasite Cryptosporidium. While piroplasms and trypanosomes were not
      detected in the blood of these animals, the overall prevalence of Cryptosporidium
      18S rDNA in faecal samples was 8.2% (7/85). Co-occurrence of multiple genotypes
      was observed in 57.1% of the infected individuals (4/7); cloning and re
      sequencing resulted in 14 sequences which broadly grouped with Cryptosporidium
      sp. rat-genotypes II and III. A novel rat-derived Cryptosporidium sp. genotype at
      the actin locus was also obtained from five animals. The relatively low infection
      rate detected, and the epidemiological data on cryptosporidiosis, do not
      conclusively support a current threat to native Australian mammals from black
      rats carrying Cryptosporidium. However, this observation is based on sampling
      limited isolates, in limited regions. Further studies, also including sampling of
      native mammals, are required on larger sample sizes and from wider geographic
      areas, to determine the significance of these findings, including the public
      health importance of Cryptosporidium spp. from rodents.

PMID- 22659227
TI  - Electronic reminders for cancer prevention: factors associated with preference
      for automated voice reminders or text messages.
AB  - OBJECTIVE: Prompting may promote engagement with behavior change interventions.
      Prompts can be delivered inexpensively via automated voice response (AVR)
      reminders or short message service (SMS) text messages. We examined the
      association between participants' characteristics and preferred reminder
      modality. METHODS: Healthy Directions 2 is a cluster randomized controlled trial
      implemented in Boston, Massachusetts to promote change in multiple behavioral
      cancer risk factors. At baseline (2009), participants completed a survey
      assessing socio-demographics, health status, height/weight, and factors
      associated with technology. One-third of participants randomized to receive the
      intervention (n=598) were randomized to receive automated reminders, with
      participants selecting modality. RESULTS: 28% (167/598) of participants selected
      SMS reminders. Controlling for clustering by primary care provider, younger
      participants (OR=0.97, 95% CI=(0.95, 0.99), p<0.01), those most comfortable with
      computers (very uncomfortable OR=0.54, 95% CI=(0.29, 1.01), p<=0.05: referent
      group = very comfortable), and those who frequently sent/received text messages
      (never OR=0.09 CI=(0.04, 0.16) p<0.01; 1-3 times/month OR=0.38, 95% CI=(0.15,
      0.93) p=0.04: referent group=1-5 times/week) were more likely to choose SMS.
      CONCLUSIONS: Interventions should make both modalities available to ensure that
      more participants can benefit from prompting. Studies examining the effect of
      automated reminders may have reduced effectiveness or generalizability if they
      employ only one modality.

PMID- 22659229
TI  - Evaluation of the performance of selected in-house and commercially available PCR
      and real-time PCR assays for the detection of Leishmania DNA in canine clinical
      samples.
AB  - Protozoa of the genus Leishmania are the causative agents of leishmaniosis.
      Although the polymerase chain reaction (PCR) has proved very effective in the
      detection of Leishmania DNA, a standardized method does not exist. In this study
      we attempt a comparative evaluation between one real time PCR (Method D), two in
      house (Methods A and C), and a commercially available PCR assay (Method B) for
      the detection of Leishmania DNA, in order to support reliable diagnostic
      investigation of leishmaniosis. This evaluation was performed in regard to
      relative specificity and sensitivity, minimum detection limit (MDL),
      repeatability and reproducibility using cultured isolates and clinical samples.
      All the methods under study produced the expected result with the positive and
      negative controls. However with regard to clinical samples, Method C showed a
      statistically significant higher level of positivity. Relative sensitivity and
      specificity of Methods A, B and D in comparison to C was calculated respectively
      at 50.7%, 43%, 40%, and 90.8%, 93.4% and 89.5%. The MDL for Methods A-D was
      defined respectively at 30.7, 5, 3.7, and 5 promastigotes/ml. Repeatability and
      reproducibility were excellent in all cases with only the exception of Method A
      regarding reproducibility with a different brand of PCR reagents. The results
      that were recorded indicate that evaluation of PCR assays before their
      application for research and clinical diagnosis can provide useful evidence for
      their reliable application. Within this context the use of internal amplification
      controls and the confirmation of the specificity of the amplification product is
      recommended.

PMID- 22659230
TI  - Effect of giardiasis combined with low-protein diet on intestinal absorption of
      glucose and electrolytes in gerbils.
AB  - Studies have shown that symptomatic infection by Giardia lamblia causes acute or
      chronic diarrhea, dehydration, abdominal pain and malabsorption, leading to
      undernutrition and weight loss. The aim of the present study was to evaluate the
      effects of giardiasis and its combination with a low-protein diet on the
      intestinal absorption of glucose and electrolytes in gerbils. The intestinal
      absorption of glucose, sodium and potassium was investigated in male gerbils
      weighing 46-64 g (n>=5). A Tyrode solution containing twice the glucose, sodium
      and potassium concentration (pH 7.4) was infused through the intestinal loops for
      40 min. Glucose absorption was not significantly affected by diet and infection.
      However, there was a significant increase in sodium absorption in the Giardia
      infected group (57.2+/-6.1, p<0.05) in comparison to the control, low-protein
      diet and low-protein diet+Giardia-infected groups (8.9+/-6.5, 2.8+/-11.1 and
      0.8+/-7.9, respectively; p<0.05). Moreover, potassium was absorbed in the Giardia
      infected group (0.45+/-0.30), while the other groups exhibited potassium
      secretion. A low-protein diet and Giardia infection had no influence over glucose
      absorption. However, Giardia infection increased sodium and potassium uptake,
      suggesting a compensatory mechanism for maintaining homeostasis after likely
      hypernatremia and hypokalemia caused by the diarrhea that accompanies giardiasis.

PMID- 22659231
TI  - Neurotoxic metal coexposures and neurodevelopment.

PMID- 22659232
TI  - In silico prediction of dermal penetration rate of chemicals from their molecular
      structural descriptors.
AB  - The dermal penetration rate of some volatile and non-volatile organic compounds
      was estimated by quantitative structure-activity relationship approaches by using
      interpretable molecular descriptors. Linear and nonlinear models were developed
      using multiple linear regressions (MLR) and artificial neural network (ANN)
      methods. Robustness and reliability of the constructed MLR and ANN models were
      evaluated by using the leave-one-out cross-validation method, which produces the
      statistics of Q(MLR)(2)=0.786, Q( ANN)(2)=0.833 for non-volatiles and
      Q(MLR)(2)=0.639, Q( ANN)(2)=0.712 for volatile compounds. Furthermore, the
      chemical applicability domains of these models were determined via leverage
      approach. The results of this study indicated the ability of developed QSAR
      models in the prediction of dermal penetration rate of various chemicals from
      their calculated molecular descriptors.

PMID- 22659234
TI  - A comprehensive modeling and vibration analysis of AFM microcantilevers subjected
      to nonlinear tip-sample interaction forces.
AB  - Precise and accurate representation of an Atomic Force Microscopy (AFM) system is
      essential in studying the effects of boundary interaction forces present between
      the probe's tip and the sample. In this paper, a comprehensive analytical model
      for the AFM system utilizing a distributed-parameters based approach is proposed.
      More specifically, we consider two important attributes of these systems; namely
      the rotary inertia and shear deformation when compared with the Euler-Bernoulli
      beam theory. Moreover, a comprehensive nonlinear interaction force is assumed
      between probe's and sample in order to reveal the response of the system more
      realistically. This nanoscale interaction force is based on a general form
      consisting of both attractive and repulsive components as well as a function of
      the tip-sample distance and the microcantilever's base and sample oscillations.
      Mechanical properties of the sample could interact with the nanomechanical
      coupling field between the probe' tip and sample and be implemented in studying
      the composition information of the sample and the ultra-small features inside it.
      Therefore, by modulating the dynamics of the AFM system such as the driving
      amplitude of the microcantilever the procedure for the subsurface imaging is
      described. The presented approach here could be implemented for designing the AFM
      probes by examining the tip-sample interaction forces dominant by the van der
      Waals forces. Several numerical case studies are presented and the force-distance
      diagram reveals that the proposed nonlinear nanomechanical force along with the
      distributed-parameters model for the microcantilever is able to fulfill the
      mechanics of the Lennard-Jones potential.

PMID- 22659233
TI  - Structure-toxicity relationship of chloroacetanilide herbicides: relative impact
      on soil microorganisms.
AB  - The research was carried out to ascertain the effect of three chloroacetanilide
      herbicides, alachlor, butachlor and pretilachlor on soil microbial biomass growth
      and activity. Laboratory experiments were performed in a silty clay loam soil to
      relate changes of soil enzymatic activity to the herbicide persistence under
      laboratory condition up to 42 days at three application rates. The results showed
      that all the three herbicides caused enhancement of dehydrogenase activity.
      Higher concentrations of herbicide resulted in enhancement of the enzymatic
      activity. In addition, a similar trend was observed in beta-glucosidase and acid
      phosphatase activity, although urease activity decreased upon incubation for 42
      days as compared with initial soil incubation values. Based on the extent of
      impact for dehydrogenase activity in soil, the order was
      pretilachlor>alachlor>butachlor; whereas in case of urease activity, the order
      changed to pretilachlor>butachlor>alachlor. The soil half-lives of alachlor,
      butachlor and pretilachlor respectively, were 9.3, 12.7 and 7.3 days, which could
      be accounted for in terms of their respective chemical structures, as well as
      variable adsorption, degradation, differential effects of the agents on soil
      microbes. Soil management practices and the differing physicochemical properties
      of the herbicides may contribute to their rates of decay in soil.

PMID- 22659235
TI  - The T-Matrix method in electron energy loss and cathodoluminescence spectroscopy
      calculations for metallic nano-particles.
AB  - In this paper, we present the application of the T-Matrix method (TMM) for the
      calculation of Electron Energy Loss Spectra (EELS), cathodoluminescence spectra
      (CLS) and far-field patterns produced by metallic nano-particles. Being
      frequently used in electromagnetic scattering calculations, the TMM provides an
      efficient tool for EELS calculations as well and can be employed, e.g. for the
      investigation of nano-antennas.

PMID- 22659236
TI  - Phenylboronic acid-functionalized glycopolymeric nanoparticles for
      biomacromolecules delivery across nasal respiratory.
AB  - The aim of this study was to explore the potential of the mucoadhesive and enzyme
      inhibitory phenylboronic acid-functionalized glycopolymeric nanoparticles as
      carriers for the nasal delivery of biomacromolecules. The glycopolymers were
      prepared by the random copolymerization of 3-acrylamidophenylboronic acid and N
      acetyl glucosamine. Insulin, as a model, was encapsulated within self-assembled
      glypolymeric nanoparticles. Nanoparticle size, insulin loading, and insulin
      release were characterized. In vitro cytotoxicity experiment showed the
      glycopolymers were cytocompatible (>= 80% cell viability). Adhesiveness was
      determined from the absorption amount of mucin, reaching up to 1180 MUg/mL.
      Moreover, the results obtained from in vivo administration of insulin-loaded
      p(AAPBA-r-MAGA) nanoparticles to rats evidenced that the nanoparticles enhanced
      insulin absorption across the nasal mucosal barrier and did not induce irritation
      of nasal mucosa. Thus, insulin-loaded nanoparticles were able to significantly
      decrease plasma glucose levels (more than 35% reduction). These results suggest
      that p(AAPBA-r-MAGA) nanoparticles have potential application for the nasal
      delivery of biomacromolecules.

PMID- 22659237
TI  - Genome-wide analysis of hepatic gene silencing in hepatoma cell variants.
AB  - Genome-wide gene expression profiling was carried out on rat hepatoma cells and
      compared to profiles of hepatoma "variant" cell lines derived via a stringent
      selection protocol that enriches for rare cells (<1 in 100,000 cells) that fail
      to drive liver function. Results show 132 genes that are strongly (>5-fold)
      repressed in each of the four variant cell lines tested. An additional 68 genes
      were repressed in 3 of 4 variant cell lines. Importantly, several of the
      repressed genes are members of transcriptional activation pathways, suggesting
      that they may contribute to maintaining the hepatic phenotype. Ectopic expression
      of the HNF1A gene in a variant cell line resulted in activation of 56 genes, 37
      of which were included in the repressed data set. These data suggest that a high
      level of reprogramming occurs when hepatoma cells convert to a non-differentiated
      phenotype, a process that can be partially reversed by the introduction of
      transcription factors.

PMID- 22659238
TI  - Population-ethnic group specific genome variation allele frequency data: a
      querying and visualization journey.
AB  - National/ethnic mutation databases aim to document the genetic heterogeneity in
      various populations and ethnic groups worldwide. We have previously reported the
      development and upgrade of FINDbase (www.findbase.org), a database recording
      causative mutations and pharmacogenomic marker allele frequencies in various
      populations around the globe. Although this database has recently been upgraded,
      we continuously try to enhance its functionality by providing more advanced
      visualization tools that would further assist effective data querying and
      comparisons. We are currently experimenting in various visualization techniques
      on the existing FINDbase causative mutation data collection aiming to provide a
      dynamic research tool for the worldwide scientific community. We have developed
      an interactive web-based application for population-based mutation data
      retrieval. It supports sophisticated data exploration allowing users to apply
      advanced filtering criteria upon a set of multiple views of the underlying data
      collection and enables browsing the relationships between individual datasets in
      a novel and meaningful way.

PMID- 22659239
TI  - Potential G-quadruplex formation at breakpoint regions of chromosomal
      translocations in cancer may explain their fragility.
AB  - Genetic alterations like point mutations, insertions, deletions, inversions and
      translocations are frequently found in cancers. Chromosomal translocations are
      one of the most common genomic aberrations associated with nearly all types of
      cancers especially leukemia and lymphoma. Recent studies have shown the role of
      non-B DNA structures in generation of translocations. In the present study, using
      various bioinformatic tools, we show the propensity of formation of different
      types of altered DNA structures near translocation breakpoint regions. In
      particular, we find close association between occurrence of G-quadruplex forming
      motifs and fragile regions in almost 70% of genes involved in rearrangements in
      lymphoid cancers. However, such an analysis did not provide any evidence for the
      occurrence of G-quadruplexes at the close vicinity of translocation breakpoint
      regions in nonlymphoid cancers. Overall, this study will help in the
      identification of novel non-B DNA targets that may be responsible for generation
      of chromosomal translocations in cancer.

PMID- 22659240
TI  - CancerProView: a graphical image database of cancer-related genes and proteins.
AB  - We have developed a graphical image database CancerProView (URL:
      http://cancerproview.dmb.med.keio.ac.jp/php/cpv.html) to assist the search for
      alterations of the motifs/domains in the cancer-related proteins that are caused
      by mutations in the corresponding genes. For the CancerProView, we have collected
      various kinds of data on 180 cancer-related proteins in terms of the
      motifs/domains, genomic structures of corresponding genes, and 109 charts of the
      protein interaction pathways. Moreover, we have collected the relevant data on
      1041 reference genes including 197 non-cancer disease-associated genes, and the
      nucleotide sequences for 2011 full-length cDNA's and the alternatively spliced
      transcript variants. Thus, the CancerProView database system would provide
      valuable information to facilitate basic cancer research as well as for designing
      new molecular diagnosis and drug discovery for cancers. The CancerProView
      database can be operated via Internet with any Web browser, and the system is
      freely available to interested users without ID and password.

PMID- 22659241
TI  - Nanomedicine applications towards the cure of HIV.
AB  - Combination antiretroviral therapy (cART) successfully suppresses HIV
      replication. However, daily and lifelong treatment is necessary to manage patient
      illness because cART neither eradicates infected cells from reservoirs nor
      reconstitutes HIV-specific immunity that could kill infected cells. Toward the
      cure of HIV, different nanomedicine classes have been developed with the
      following disease-modifying properties: to eradicate the virus by activation of
      latently infected CD4+ T-cells and reservoirs flushing; to kill the infected
      cells in the reservoirs by boosting of HIV-specific T cells; and to prevent
      infection by the use of microbicides with improved epithelial penetration and
      drug half-life. Preclinical and clinical trials consistently demonstrated that
      DermaVir, the most advanced nanomedicine, induces long-lasting memory T-cell
      responses and reduces viral load in comparison with placebo. DermaVir and the
      nanomedicine pipelines have the potential to improve the health of HIV-infected
      people at lower costs, to decrease antiretroviral drug exposure, and to
      contribute to the cure of HIV/AIDS. FROM THE CLINICAL EDITOR: Despite the leaps
      and bounds in the development of antiretroviral therapy, HIV remains a
      significant public health challenge. In this review, applications of nanomedicine
      based technologies are discussed in the context of HIV treatment, including
      virus elimination by activation of latently infected CD4+ T-cells; infected cell
      elimination in the reservoirs by boosting HIV-specific T cells, and by preventing
      infection by the use of microbicides with improved epithelial penetration and
      drug half-life.

PMID- 22659242
TI  - Advantage of Guarana (Paullinia cupana Mart.) supplementation on cadmium-induced
      damages in testis of adult Wistar rats.
AB  - Paullinia cupana is an Amazonian bush whose seeds have long been used in folk
      medicine. However, most of the therapeutic properties attributed to this plant
      are broad and nonspecific, although an antioxidant activity has been reported. 
      On the other hand, cadmium is a heavy metal known for increasing free radicals,
      hence resulting in cellular oxidative damages. This study was designed to
      evaluate whether Paullinia cupana is able to reduce cadmium-induced morphological
      impairment in Wistar rat testis. Adult male Wistar rats 110 days old were ip
      injected with cadmium (1.15 mg/kg BW [body weight]) and subsequently treated with
      P. cupana during 56 days.  Furthermore, groups receiving either P. cupana extract
      or cadmium are mentioned. After the treatment period, testis samples were
      subjected to histological and stereological analyses. Moderate to severe
      testicular impairments were shown by the animals exposed to cadmium. However, the
      animals supplemented with P. cupana after cadmium exposure showed a significant
      decrease in the proportion of damaged seminiferous tubules. Also, P. cupana
      supplementation was effective in maintaining the number of Leydig cells per
      testis in the animals exposed to cadmium. In conclusion, P. cupana
      supplementation was partially efficient in preventing cadmium from damaging the
      testis of adult Wistar rats.

PMID- 22659243
TI  - Frontiers in preclinical safety biomarkers: microRNAs and messenger RNAs.
AB  - The measurement of plasma microRNAs (miRNAs) and messenger RNAs (mRNAs) is the
      most recent effort to identify novel biomarkers in preclinical safety. These
      genomic markers often display tissue-specific expression, may be released from
      the tissues into the plasma during toxic events, change early and with high
      magnitude in tissues and in the blood during specific organ toxicities, and can
      be measured using multiplex formats. Their validation as biomarkers has been
      challenged by the technical difficulties. In particular, the concentration of
      miRNAs in the plasma depends on contamination by miRNAs originating from blood
      cells and platelets, and the relative fraction of miRNAs in complexes with
      Argonaute 2, high-density lipoproteins, and in exosomes and microvesicles. In
      spite of these hurdles, considerable progress has recently been made in assessing
      the potential value of miRNAs in the clinic, especially in cancer patients and
      cardiovascular diseases. The future of miRNAs and mRNAs as biomarkers of disease
      and organ toxicity depends on our ability to characterize their kinetics and to
      establish robust collection and measurement methods. This review covers the basic
      biology of miRNAs and the published literature on the use of miRNAs and mRNAs as
      biomarkers of specific target organ toxicity.

PMID- 22659244
TI  - Claudin-3 and Clara cell 10 kDa protein as early signals of cigarette smoke
      induced epithelial injury along alveolar ducts.
AB  - Smoking-associated chronic obstructive pulmonary disease is characterized by
      inflammation, changes affecting small airways, and development of emphysema.
      Various short- and long-term models have been introduced to investigate these
      processes. The aim of the present study was to identify markers of early
      epithelial injury/adaptation in a short-term animal model of cigarette smoke
      exposure. Initially, male BALB/c mice were exposed to smoke from one to five
      cigarettes and lung changes were assessed 4 and 24 hr after smoking cessation.
      Subsequently, animals were exposed to smoke from five cigarettes for 2
      consecutive days and lungs investigated daily until the seventh postexposure day.
      Lung homogenates cytokines were determined, bronchioloalveolar fluid cells were
      counted, and lung tissue was analyzed by immunohistochemistry. Exposure to smoke
      from a single cigarette induced slight pulmonary neutrophilia. Smoke from two
      cigarettes additionally induced de novo expression of tight junction protein,
      claudin-3, by alveolar duct (AD) epithelial cells. Further increases in smoke
      exposure induced epithelial changes in airway progenitor regions. During the
      recovery period, the severity/frequency of epithelial reactions slowly decreased,
      coinciding with the switch from acute to a chronic inflammatory reaction. Claudin
      3 and Clara cell 10 kDa protein were identified as possible markers of early
      tobacco smoke-induced epithelial injury along ADs.

PMID- 22659245
TI  - Histopathological changes in the livers of rabbit fish (Siganus canaliculatus)
      following exposure to crude oil and dispersed oil.
AB  - The present study aimed to assess the impact of acute exposure to crude oil,
      dispersed oil, and dispersant alone on the liver of the rabbit fish (Siganus
      canaliculatus). Histopathological effects in the liver were observed at different
      time points (3 to 21 days) and different concentrations (3-100% water
      accommodated fraction [WAF]) to simulate a range of possible oil pollution
      events. The main alterations observed in this study include lipid accumulation,
      necrosis, bile stagnation, megalocytosis, cholangitis, and spongiosis hepatis.
      The liver of fish exposed to WAF, dispersed oil, or dispersant showed significant
      histopathologic alterations compared with the control fish (Mann-Whitney U test;
      p < .01). Reaction pattern indices (circulatory, degenerative, proliferative, and
      inflammatory changes) of treated fish differed significantly from the control
      groups. There was a significant correlation between exposure time and the
      occurrence of most lesions (Spearman correlation; p > .05). The present study
      indicates that oil pollution can cause important alterations to livers of adult
      rabbit fish and that the dispersed oil is slightly more toxic than crude oil or
      dispersant.

PMID- 22659246
TI  - Dynamic development of glucocorticoid resistance during autoimmune
      neuroinflammation.
AB  - CONTEXT: Glucocorticoids (GC) are powerful endogenous and therapeutic modulators
      of inflammation and play a critical role for controlling autoimmunity. GC
      resistance can be seen in patients with cell-mediated autoimmune disorders, but
      it is unknown whether this represents a stable trait or a state. OBJECTIVE: The
      objective of the study was to determine whether GC resistance of T cell responses
      is dynamically regulated in experimental autoimmune encephalomyelitis (EAE) and
      multiple sclerosis (MS). DESIGN: This was a translational observational study.
      PATIENTS AND ANIMALS: EAE was induced in C57BL/6 mice. A cross-sectional sample
      of 25 patients with relapsing-remitting MS was included as well as four MS
      patients during pregnancy and postpartum. MAIN OUTCOME MEASURES: Outcome measures
      included GC sensitivity of T cell proliferation and GC-mediated apoptosis.
      RESULTS: GC resistance was seen in both autoantigen-specific and nonspecific
      responses of T cells obtained from mice with EAE. GC resistance preceded clinical
      symptoms and central nervous system infiltration of immune cells. T cells
      obtained during EAE were resistant to GC-induced apoptosis, and this was linked
      to down-regulation of GC receptor-alpha expression. GC resistance in T cells was
      also seen in MS patients with radiological evidence for ongoing inflammation. GC
      resistance was absent in the MS patients during pregnancy, when relapse risk is
      decreased, but recurred postpartum, a time of increased relapse risk.
      CONCLUSIONS: These data demonstrate that GC resistance during autoimmune
      neuroinflammation is dynamically regulated. This has implications for the timing
      of steroid treatments and provides a putative pathway to explain the observed
      association between psychological stress and exacerbation of autoimmune diseases.

PMID- 22659247
TI  - Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1
      pathway.
AB  - CONTEXT: Somatotroph adenomas harboring aryl hydrocarbon receptor interacting
      protein (AIP) mutations respond less well to somatostatin analogs, suggesting
      that the effects of somatostatin analogs may be mediated by AIP. OBJECTIVE: The
      objective of the investigation was to study the involvement of AIP in the
      mechanism of effect of somatostatin analogs. DESIGN: In the human study, a 16-wk
      somatostatin analog pretreatment compared with no pretreatment. In the in vitro
      cell line study, the effect of somatostatin analog treatment or small interfering
      RNA (siRNA)/plasmid transfection were studied. SETTING: The study was conducted
      at a university hospital. PATIENTS: Thirty-nine sporadic and 10 familial
      acromegaly patients participated in the study. INTERVENTION: Interventions
      included preoperative lanreotide treatment and pituitary surgery. OUTCOME: For
      the human study, GH and IGF-I levels, AIP, and somatostatin receptor staining
      were measured. For the cell line, AIP and ZAC1 (zinc finger regulator of
      apoptosis and cell cycle arrest) expression, metabolic activity, and clone
      formation were measured. RESULTS: Lanreotide pretreatment reduced GH and IGF-I
      levels and tumor volume (all P < 0.0001). AIP immunostaining was stronger in the
      lanreotide-pretreated group vs. the surgery-only group (P < 0.001). After
      lanreotide pretreatment, the AIP score correlated to IGF-I changes in females (R
      = 0.68, P < 0.05). Somatostatin receptor staining was not reduced in samples with
      AIP mutations. In GH3 cells, 1 nm octreotide increased AIP mRNA and protein (both
      P < 0.01) and ZAC1 mRNA expression (P < 0.05). Overexpression of wild-type (but
      not mutant) AIP increased ZAC1 mRNA expression, whereas AIP siRNA knockdown
      reduced ZAC1 mRNA (both P < 0.05). The siRNA-mediated knockdown of AIP led to an
      increased metabolic activity and clonogenic ability of GH3 cells compared with
      cells transfected with a nontargeting control (both P < 0.001). CONCLUSION: These
      results suggest that AIP may play a role in the mechanism of action of
      somatostatin analogs via ZAC1 in sporadic somatotroph tumors and may explain
      their lack of effectiveness in patients with AIP mutations.

PMID- 22659248
TI  - LH-receptor gene expression in human granulosa and cumulus cells from antral and
      preovulatory follicles.
AB  - CONTEXT: Human granulosa cells (GC) acquire LH receptor (LHR) expression during
      the follicular phase of the menstrual cycle. Currently, the precise follicular
      stage is unknown, and specific roles of LH in the follicular development are not
      fully understood. OBJECTIVE: Our objective was to measure LHR gene expression on
      GC and cumulus cells (CC) from normal human follicles with diameters form 3-20
      mm. DESIGN, SETTING, AND PATIENTS: At a university hospital, GC, CC, and the
      corresponding follicular fluid (FF) were collected from patients undergoing
      fertility preservation by having one ovary frozen and patients undergoing
      infertility treatment. INTERVENTIONS: Cells and fluids were isolated from
      surgically excised ovaries or from aspirated preovulatory follicles. MAIN OUTCOME
      MEASURES: We evaluated gene expression of LHR, FSHR, androgen receptor (AR),
      aromatase (CYP19a1), and AMHR2 normalized to the GAPDH expression and associated
      with FF levels of anti-Mullerian hormone, inhibin-B, and steroids. RESULTS: LHR
      expression was maximal in GC from preovulatory follicles before ovulation
      induction. A majority of 150 antral follicles (3-10 mm in diameter) showed LHR
      expression at approximately 10% of the maximum, and LHR expression showed
      significant associations with FSHR, AR, CYP19a1, and AMHR2 and with FF estradiol
      and progesterone. Levels of FSHR continued to decline in GC as the follicular
      diameter increased. CONCLUSIONS: The LHR gene is expressed in GC of human antral
      follicles throughout the follicular phase and is significantly associated with
      expression of the CYP19a1 gene and with the corresponding FF concentrations of
      estradiol and progesterone. LH appears to affect human follicular development
      during most the follicular phase in normal women.

PMID- 22659249
TI  - Trajectory clustering of estradiol and follicle-stimulating hormone during the
      menopausal transition among women in the Study of Women's Health across the
      Nation (SWAN).
AB  - CONTEXT: Variability in the pattern of change in estradiol (E2) and FSH levels
      over the menopause transition has not been well defined. OBJECTIVE: The current
      study aimed to determine whether different trajectories of E2 and FSH could be
      identified and whether race/ethnicity and body mass index were related to the
      different trajectories. DESIGN: The Study of Women's Health Across the Nation is
      a longitudinal observational study of the menopausal transition. SETTING: Women
      aged 42-52 yr from seven participating sites were recruited and underwent up to
      11 annual visits. PARTICIPANTS: Postmenopausal women with 12 or more months of
      amenorrhea that was not due to hysterectomy/oophorectomy and who were not using
      hormone therapy before the final menstrual period participated in the study. MAIN
      OUTCOME MEASURES: Annual serum E2 and FSH levels anchored to final menstrual
      period were measured. RESULTS: Four distinct E2 trajectories and three distinct
      FSH trajectories were identified. The E2 trajectories were: slow decline (26.9%),
      flat (28.6%), rise/slow decline (13.1%), and rise/steep decline (31.5%). The FSH
      trajectories were: low (10.6%), medium (48.7%), and high (41.7%) rising patterns.
      Obesity increased the likelihood of a flat E2 and low FSH trajectory for all
      race/ethnic groups. Normal-weight Caucasian and African-American women tended to
      follow the rise/steep decline E2 and high FSH trajectories. Normal-weight
      Chinese/Japanese women tended to follow the slow decline E2 and the high/medium
      FSH trajectories. CONCLUSIONS: E2 and FSH trajectories over the menopausal
      transition are not uniform across the population of women. Race/ethnicity and
      body mass index affect the trajectory of both E2 and FSH change over the
      menopausal transition.

PMID- 22659250
TI  - Impact of male hormonal contraception on prostate androgens and androgen action
      in healthy men: a randomized, controlled trial.
AB  - CONTEXT: Male hormonal contraception (MHC) combines hypothalamic-pituitary
      gonadal axis blockade with exogenous androgen delivery to maintain extragonadal
      androgen end-organ effects. Concern exists that MHC may adversely impact prostate
      health. OBJECTIVE: The objective of the study was to determine the molecular
      impact of MHC on intraprostatic androgen concentrations and androgen action.
      DESIGN: This was a single-blind, randomized, placebo-controlled study. SETTING:
      The study was conducted at an academic medical center. PARTICIPANTS: 32 healthy
      men aged 25-55 yr participated in the study. INTERVENTION: Interventions included
      placebo, daily transdermal testosterone (T) (T-gel), T-gel +
      depomedroxyprogesterone acetate (T+DMPA), or T-gel + dutasteride daily (T+D) for
      12 wk, and prostate biopsy during treatment wk 10. MAIN OUTCOME MEASURES: Serum
      and prostate androgen concentrations and prostate epithelial-cell gene expression
      were measured. RESULTS: Thirty men completed the study. Serum T levels were
      significantly increased in T-gel and T+D groups compared with baseline (P < 0.05)
      but were decreased with the addition of DMPA. Intraprostatic androgens were no
      different from placebo with T-gel treatment. Addition of DMPA to T resulted in
      40% lower intraprostatic dihydrotestosterone (DHT) concentration (P = 0.0273 vs.
      placebo), whereas combining dutasteride with T resulted in a 90% decrease in
      intraprostatic DHT (P = 0.0012), 11-fold increased intraprostatic T (P = 0.0011),
      and 7-fold increased intraprostatic androstenedione (P = 0.0011). Significant
      differences in global or androgen-regulated prostate epithelial-cell gene
      expression were not observed. Androgen-regulated gene expression correlated with
      epithelial-cell androgen receptor and prostatic DHT in placebo, T-gel, and T+DMPA
      arms and with T and androstenedione levels in the T+D arm. CONCLUSIONS: MHC
      regimens do not markedly alter gene expression in benign prostate epithelium,
      suggesting they may not alter risk of prostate disease. Longer-term studies
      examining the impact of MHC on prostate health are needed.

PMID- 22659251
TI  - Mutations in the ANGPTL3 gene and familial combined hypolipidemia: a clinical and
      biochemical characterization.
AB  - CONTEXT: Familial combined hypolipidemia causes a global reduction of plasma
      lipoproteins. Its clinical correlates and metabolic implications have not been
      well defined. OBJECTIVE: The objective of the study was to investigate the
      genetic, clinical, and metabolic characteristics of a cohort of subjects with
      familial combined hypolipidemia. DESIGN: The design of the study included
      candidate gene screening and the comparison of the clinical and metabolic
      characteristics between carrier and noncarrier individuals. SETTING: The study
      was conducted in a general community. SUBJECTS: Participants in the study
      included individuals belonging to nine families with familial combined
      hypolipidemia identified in a small town (Campodimele) as well as from other 352
      subjects living in the same community. MAIN OUTCOMES MEASURES: Serum
      concentrations of lipoproteins, Angiopoietin-like 3 (Angptl3) proteins, and
      noncholesterol sterols were measured. RESULTS: The ANGPTL3 S17X mutation was
      found in all probands, 20 affected family members, and 32 individuals of the
      community. Two additional frame shift mutations, FsE96del and FsS122, were also
      identified in two hypocholesterolemic individuals. Homozygotes for the ANGPTL3
      S17X mutation had no circulating Angptl3 and a marked reduction of all plasma
      lipids (P < 0.001). Heterozygotes had 42% reduction in Angptl3 level compared
      with noncarriers (P < 0.0001) but a significant reduction of only total
      cholesterol and high-density lipoprotein cholesterol. No differences were
      observed in the plasma noncholesterol sterols between carriers and noncarriers.
      No association between familial combined hypolipidemia and the risk of hepatic or
      cardiovascular diseases were detected. CONCLUSIONS: Familial combined
      hypolipidemia segregates as a recessive trait so that apolipoprotein B- and
      apolipoprotein A-I-containing lipoproteins are comprehensively affected only by
      the total deficiency of Angptl3. Familial combined hypolipidemia does not perturb
      whole-body cholesterol homeostasis and is not associated with adverse clinical
      sequelae.

PMID- 22659252
TI  - In vivo suppression of plasma IL-12 levels by acute and chronic stress paradigms:
      potential mediating mechanisms and sex differences.
AB  - Interleukin-12 (IL-12) is a major pro-inflammatory cytokine, which promotes cell
      mediated immunity and T(H)1 differentiation. In vitro studies indicated
      suppression of IL-12 production by several stress-related factors, but no effects
      of behavioral stress were shown on plasma IL-12 levels. Therefore, in the current
      study we (i) examined the in vivo effects of various behavioral and
      pharmacological stress paradigms on baseline plasma IL-12 levels; (ii) compared
      these in vivo findings to those obtained following in vitro stimulation of
      leukocytes from the same rats; and (iii) assessed potential sexual dimorphism in
      these outcomes. The findings indicated that plasma IL-12 levels were
      significantly reduced by social confrontation, wet-cage exposure, surgery, and
      the administration of corticosterone, epinephrine, or prostaglandin-E(2).
      Notably, most in vivo impacts on plasma levels were not evident when assessed in
      vitro. The IL-12-reducing effects of wet-cage exposure, and of corticosterone and
      epinephrine administration, were significantly greater in males than in females,
      although females exhibited greater total corticosterone levels following stress.
      The duration of acute stressors predicted the degree of IL-12 reduction, but more
      prolonged stressors did not. Furthermore, seven days of alternating behavioral
      stressors reduced plasma IL-12 levels more than 14 days. These findings suggest
      animals' behavioral habituation to stress conditions, or a specific immune
      mechanism restricting the duration of IL-12 reduction. Overall, our findings
      indicate a generic and robust stress-induced reduction in plasma IL-12 levels,
      and suggest epinephrine, corticosterone, and prostaglandin-E(2), as potential
      mediators that should be scrutinized in vivo in the context of natural
      physiological stress responses.

PMID- 22659253
TI  - Susceptibility of different developmental stages of large pine weevil Hylobius
      abietis (Coleoptera: Curculionidae) to entomopathogenic fungi and effect of
      fungal infection to adult weevils by formulation and application methods.
AB  - The large pine weevil, Hylobius abietis, is a major pest in European conifer
      forests causing millions of Euros of damage annually. Larvae develop in the
      stumps of recently felled trees; the emerging adults feed on the bark of
      seedlings and may kill them. This study investigated the susceptibility of
      different developmental stages of H. abietis to commercial and commercially
      viable isolates of entomopathogenic fungi, Metarhizium and Beauveria. All the
      developmental stages of H. abietis can be killed by Metarhizium robertsii,
      Metarhizium brunneum, and Beauveria bassiana. The most virulent isolate of M.
      robertsii ARSEF4556 caused 100% mortality of pupae, larvae and adults on day 4, 6
      and 12, respectively. This strain was further tested against adult weevils in
      different concentrations (10(5)-10(8) conidia cm(-2) or ml(-1)) using two types
      of fungal formulation: 'dry' conidia and 'wet' conidia (suspended in 0.03% aq.
      Tween 80) applied on different substrates (tissue paper, peat and Sitka spruce
      seedlings). 'Dry' conidia were more effective than 'wet' conidia on tissue paper
      and on spruce or 'dry' conidia premixed in peat. The LC(50) value for 'dry'
      conidia of isolate ARSEF4556 was three folds lower than 'wet' conidia on tissue
      paper. This study showed that 'dry' conidia are more effective than 'wet'
      conidia, causing 100% adult mortality within 12 days. Possible strategies for
      fungal applications are discussed in light of the high susceptibility of larvae
      and pupae to fungal pathogen.

PMID- 22659254
TI  - Putting the parts together: combining in vitro methods to test for skin
      sensitizing potentials.
AB  - Allergic contact dermatitis is a common skin disease and is elicited by repeated
      skin contact with an allergen. In the regulatory context, currently only data
      from animal experiments are acceptable to assess the skin sensitizing potential
      of substances. Animal welfare and EU Cosmetic Directive/Regulation call for the
      implementation of animal-free alternatives for safety assessments. The mechanisms
      that trigger skin sensitization are complex and various steps are involved.
      Therefore, a single in vitro method may not be able to accurately assess this
      endpoint. Non-animal methods are being developed and validated and can be used
      for testing strategies that ensure a reliable prediction of skin sensitization
      potentials. In this study, the predictivities of four in vitro assays, one in
      chemico and one in silico method addressing three different steps in the
      development of skin sensitization were assessed using 54 test substances of known
      sensitizing potential. The predictivity of single tests and combinations of these
      assays were compared. These data were used to develop an in vitro testing scheme
      and prediction model for the detection of skin sensitizers based on protein
      reactivity, activation of the Keap-1/Nrf2 signaling pathway and dendritic cell
      activation.

PMID- 22659255
TI  - Gastroesophageal reflux.

PMID- 22659256
TI  - Bronchopulmonary dysplasia.

PMID- 22659258
TI  - Child and Adolescent Gender Center: a multidisciplinary collaboration to improve
      the lives of gender nonconforming children and teens.

PMID- 22659257
TI  - Performance-enhancing drugs.

PMID- 22659260
TI  - Complementary, holistic, and integrative medicine: therapies for neurodevelopment
      in preterm infants.

PMID- 22659262
TI  - Corneal abrasions.

PMID- 22659261
TI  - Index of suspicion. Case 1: Infant who has respiratory distress. Case 2: Abnormal
      behavior, seizures, and altered sensorium in a 7-year-old boy. Case 3: Fever and
      dysphagia in a 4-year-old girl.

PMID- 22659263
TI  - Vesicular rash in a 28-day-old girl.

PMID- 22659265
TI  - Potential role of LMP2 as an anti-oncogenic factor in human uterine
      leiomyosarcoma: morphological significance of calponin h1.
AB  - Uterine leiomyosarcoma (LMS) is a highly metastatic smooth muscle neoplasm for
      which calponin h1 is suspected to have a biological role as a tumor-suppressor.
      We earlier reported that LMP2-null mice spontaneously develop uterine LMS through
      malignant transformation of the myometrium, thus implicating this protein as an
      anti-tumorigenic candidate as well. In the present study, we show that LMP2 may
      negatively regulate LMS independently of its role in the proteasome. Moreover,
      several lines of evidence indicate that although calponin h1 does not directly
      influence tumorigenesis, it clearly affects LMP2-induced cellular morphological
      changes. Modulation of LMP2 may lead to new therapeutic approaches in human
      uterine LMS.

PMID- 22659266
TI  - Anti-tumor and immunomodulating activities of a polysaccharide from the root of
      Sanguisorba officinalis L.
AB  - A water-soluble polysaccharide, named as SOWP, was extracted and fractioned from
      the roots of Sanguisorba officinalis L. by DEAE-Sepharose anion exchange and
      Sepharose 6 Fast Flow column chromatography. The monosaccharide composition of
      SOWP determined by gas chromatography (GC) identified it was composed of glucose
      (68.5%), arabinose (13.2%), rhamnose (8.9), xylose (6.2) and galactose (3.0%). At
      the dose of 50, 100, and 200 mg/kg, SOWP not only significantly inhibited the
      growth of mouse transplantable tumor, but also remarkably increased the spleen
      index and promoted splenocytes proliferation, macrophage phagocytosis and the
      production of serum cytokines IL-2, TNF-alpha and IFN-gamma in Sarcoma 180
      bearing mice. However, no direct cytotoxic activity against Sarcoma 180 cells was
      observed. The anti-tumor activity of the polysaccharide from S. officinalis maybe
      achieved by not directly cytotoxicity but rather immunopotentiation.

PMID- 22659267
TI  - Are bioprostheses associated with better outcome than mechanical valves in
      patients with chronic kidney disease requiring dialysis who undergo valve
      surgery?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether patients with chronic kidney disease
      who required dialysis that undergo valve surgery have better surgical recovery
      rates with bioprostheses than with mechanical valves. Altogether more than 96
      papers were found using the reported search, of which 12 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. Patients with end stage renal disease (ESRD)
      undergoing cardiac surgery are very fragile, with high in-hospital mortality
      rates (13-36%) and limited life expectancy (15-42 months in selected studies).
      Two studies outlined that diabetic ESRD, neurological impairment, age at the
      operation and poor ventricular function are the strongest predictors of early and
      late morbidity and mortality. Based on American Heart Association/American
      College of Cardiology (AHA/ACC) 1998 valvular guidelines, bioprostheses were
      considered a contraindication in dialysis patients; this statement derived from
      anecdotal reports of accelerated valve degeneration. Structural valve
      deterioration was reported in only 5 of 1347 patients who received bioprosthesis
      through the studies and independent from implantation site. Likelihood of
      degeneration is low, with a calculated valve-excision rate of 7%, and occurred in
      a broad range of time (from 10 to 156 months). The AHA/ACC 2006 valvular revised
      guidelines removed the previous statement (1998) of class IIa recommendation for
      mechanical valves and class III for tissue valves; in the focus update of 2008,
      there is still no specific indication for valve selection in dialysis patients,
      but difficulties in maintaining anticoagulation in these patients was noted.
      Stroke, haemorrhage and gastro-intestinal bleeding events occurred in almost 15%
      of patients with mechanical valves during the follow-up, while bioprostheses
      showed an average event rate of 3.9%. All but one of the selected studies
      reported no differences in survival between mechanical and biological valves; in
      five of seven studies, the patients who received bioprostheses were older
      (mechanical vs biological average 53 years vs 61.4 years), in one study, patients
      had undergone dialysis for longer period of time, and, in another study, they had
      suffered from more previous myocardial infarction (mechanical vs biological 9.1%
      vs 36.2%). Therefore, survivals have been biased in favour of mechanical valves.
      Taking together these data, biological valves are a suitable treatment for
      dialysis-dependent patients and, while not superior to mechanical valves in
      survival due to the aforementioned study biases, exhibit lower valve-related and
      anti-coagulation related events.

PMID- 22659268
TI  - The French airbridge for circulatory support in the Carribean.
AB  - OBJECTIVES: We report the assessment and the activities for the first year of our
      airborne circulatory support mobile unit (CSMU) in the French Caribbean. METHODS:
      From January 2010 to June 2011, 12 patients (mean age = 35.7 years; range: 15-62
      years; sex ratio = 1:1) were attended outside Martinique by our CSMU and
      transferred to our unit by air. RESULTS: Eight patients had acute respiratory
      distress syndrome and were assisted by veno-venous extra corporeal membrane
      oxygenation (ECMO) four had refractory cardiogenic shock, assisted by extra
      corporeal life support (ECLS). The average air transfer distance for patients was
      912 km (range: 198-1585 km). The average flying time was 124 min (range: 45-255
      min). The aircraft used were helicopter, military transport or private jet. The
      setting-up of assistance devices and transfer of patients was uneventful. One
      patient subsequently benefited from heart transplantation after long-term
      circulatory support. One patient died under ECMO support after 51 days of
      assistance and another died on the 60th day after withdrawal of ECLS.
      CONCLUSIONS: CSMUs can be very efficient in providing support to patients in
      refractory shock, when remote from a cardiac surgery centre. The airborne
      transfer of patients on ECMO/ECLS can be achieved safely, even over long
      distances.

PMID- 22659269
TI  - Transcatheter valve implantation: damage to the human aorta after valved stent
      delivery system exposure--an in vitro study.
AB  - Transcatheter heart valve implantation can be performed transapically and
      transfemorally. The transfemoral way to the aortic valve is significantly longer
      than the transapical one. The aim of this study was to analyse the intima of 15
      human aortas after the deployment of different conventional valved stent delivery
      systems. Fifteen human aortas have been analysed (77 +/- 8.4 years). These aortas
      were preserved with formalin and explanted from the common iliac arteries to the
      ascending aorta. After protocolling all relevant vascular parameters, the
      deployment force of different conventional valved stent delivery systems was
      analysed. After that, the intima was closely investigated by endoscopy. The
      deployment force of the old catheter was not different from the actual system.
      The endoscopic investigation revealed significant intimal damages in all parts of
      the aorta after deployment of the delivery system. This study demonstrated that
      the passage to the aortic valve can result in significant intimal damage
      regardless of the used deployment catheter. Efforts are necessary to lower the
      profile of the deployment devices to increase their flexibility. The intima of
      the aorta and possible damage have to get back into the physicians' focus to
      avoid possible late aortic complications.

PMID- 22659270
TI  - A further contribution to the delineation of the 17q21.31 microdeletion syndrome:
      central nervous involvement in two Italian patients.
AB  - The 17q21.31 microdeletion syndrome is a genetic disorder characterized by
      intellectual disability, facial dysmorphisms and a typical behavioral phenotype.
      Patients are usually described as friendly and cooperative but they can also show
      behavioral problems such as hyperactivity, bad humor, temper tantrums and poor
      interaction. Central nervous system involvement includes callosal
      dysgenesis/absence, enlargement of lateral ventricles and abnormalities of
      cyngulate gyrus. We report on two Italian patients with the 17q21.31
      microdeletion syndrome better emphasizing neuroimaging and neuropsychological
      characteristics. In particular, we carried out an assessment of intellectual
      efficiency and behavior that turned out to be within the mild-moderate range of
      mental retardation, as already reported in the literature. To the best of our
      knowledge this is the first report of a patient with the 17q21.31 microdeletion
      and a Chiari malformation type 1 coexisting with a mild anomaly of medulla
      oblongata. This malformation should be considered in patients with the 17q21.31
      microdeletion syndrome, presenting suggestive symptoms (headache, neck pain,
      cerebellar signs or muscle weakness).

PMID- 22659271
TI  - 2q23.1 microdeletion of the MBD5 gene in a female with seizures, developmental
      delay and distinct dysmorphic features.
AB  - We report a 2-year-old female who initially presented with seizures,
      developmental delay and dysmorphic features and was found to have a 0.3 Mb
      deletion at chromosome 2q23.1 encompassing the critical seizure gene, MBD5. Her
      distinct physical features include bifrontal narrowing with brachycephaly, low
      anterior hairline, hypotonic facial features with short upturned nose, flat nasal
      bridge, hypertelorism, tented upper lip with everted lower lip, downturned
      corners of her mouth, and relatively coarse facial features including thickened
      tongue. She also had a short neck, brachytelephalangy, clinodactyly, and
      hypertrichosis. At 31/2 years she developed progressive ataxia and lost
      vocabulary at the age of 4. Regression has been reported in one other case of
      MBD5 deletion. MBD5 is a member of the methyl binding gene family and appears to
      be responsible for regulating DNA methylation in the central nervous system. Our
      patient was entirely deleted for the MBD5 gene with partial loss of the EPC2
      gene, which suggests that haploinsufficiency of MBD5 is responsible for the
      distinct phenotype observed. This supports the hypothesis that MBD5 is indeed the
      critical gene implicated for the findings seen in patients with deletions of
      chromosome 2q23.1. Further studies are necessary to delineate the role that the
      MBD5 gene plays in the development of the brain and these specific physical
      characteristics.

PMID- 22659272
TI  - Arabidopsis-derived shrimp viral-binding protein, PmRab7 can protect white spot
      syndrome virus infection in shrimp.
AB  - White spot syndrome virus is currently the leading cause of production losses in
      the shrimp industry. Penaeus monodon Rab7 protein has been recognized as a viral
      binding protein with an efficient protective effect against white spot syndrome
      infection. Plant-derived recombinant PmRab7 might serve as an alternative source
      for in-feed vaccination, considering the remarkable abilities of plant expression
      systems. PmRab7 was introduced into the Arabidopsis thaliana T87 genome.
      Arabidopsis-derived recombinant PmRab7 showed high binding activity against white
      spot syndrome virus and a viral envelope, VP28. The growth profile of Arabidopsis
      suspension culture expressing PmRab7 (ECR21# 35) resembled that of its
      counterpart. PmRab7 expression in ECR21# 35 reached its maximum level at 5 mg g(
      1) dry weight in 12 days, which was higher than those previously reported in
      Escherichia coli and in Pichia. Co-injection of white spot syndrome virus and
      Arabidopsis crude extract containing PmRab7 in Litopenaeus vannamei showed an 87%
      increase in shrimp survival rate at 5 day after injection. In this study, we
      propose an alternative PmRab7 source with higher production yield, and cheaper
      culture media costs, that might serve the industry's need for an in-feed
      supplement against white spot syndrome infection.

PMID- 22659274
TI  - Biomarkers of maternal diabetes and its complication in pregnancy.
AB  - There are specific biomarkers - indicators of normal and abnormal processes - in
      diabetic pregnancies that predict the degree of diabetic control as well as
      embryonic and fetal growth and development. They can be detected in maternal
      blood, amniotic fluid or in the cord plasma of the newborn infant. While the cord
      plasma levels are of little clinical relevance because they do not allow us to
      interfere with the outcome of pregnancy, biomarkers in maternal blood or amniotic
      fluid may help us to better control the outcome of diabetic pregnancies.
      Important biomarkers in maternal blood are fasting glucose, HbA1c and IGFs.
      Relevant biomarkers in amniotic fluid are insulin, erythropoietin and markers of
      bone formation and resorption. Cord plasma biomarkers include IGFs, leptin,
      adiponectin, resistin, markers of oxidative stress and of hypoxia. Whether these
      biomarkers can be predictors of long term outcome in infants of diabetic mothers
      is yet to be determined.

PMID- 22659273
TI  - Preliminary findings of the developmental effects of in utero exposure to
      topiramate.
AB  - There are relatively few studies that have looked at the longer-term
      developmental effects of intra-uterine topiramate exposure. The purpose of this
      report is to describe preliminary findings of the developmental outcomes of a
      group of nine children of preschool age (3-6 years, 11 months), exposed in utero
      to topiramate (TX) monotherapy, as compared to a control group of 18 children.
      The groups were compared on developmental measures of visual, fine and gross
      motor function as well as measures of behavior and cognitive functions. Results
      showed that the TX group performed significantly worse than the control group for
      almost all measures, with the most clearly delineated differences in the area of
      cognitive functioning. While the study group is small, and only preliminary
      conclusions may be inferred, it appears that TX exposure may have subtle effects
      on the development of children in a range of areas including motor function,
      cognition, and behavior.

PMID- 22659275
TI  - Cerasomal doxorubicin with long-term storage stability and controllable sustained
      release.
AB  - Liposomal nanohybrid cerasomes display a remarkable ability to maintain their
      size and retain encapsulated doxorubicin (DOX) over a period of 90days under
      storage conditions in solution compared with liposomes and liposils. Cerasomes
      retained 92.1+/-2.9% of the drug payload after 90days storage, much more than
      liposomes (35.2+/-2.5%) and liposils (53.2+/-5.5%). Under physiologically
      relevant conditions cerasomes exhibit a low initial burst in the first 5h and
      subsequent sustained release of DOX over the next 150h. Moreover, the magnitude
      of the initial burst and the rate of sustained release of DOX from cerasomes can
      be modulated by incorporating dipalmitoylphosphatidylglycerol (DPPG) in the
      cerasome structure and altering the ratios of the cerasome-forming lipid and
      phospholipids. Consequently, a wide range of release profiles can be achieved by
      altering the vesicle composition. Finally, human ovarian cancer cells are
      effectively killed by DOX released from cerasomes. Together these results suggest
      that cerasomes may be a promising drug delivery system for the long-term storage
      and controllable sustained release of the anticancer drug DOX.

PMID- 22659276
TI  - Raman spectroscopy of the borate mineral ameghinite NaB3O3(OH)4.
AB  - The molecular structure of the sodium borate mineral ameghinite NaB(3)O(3)(OH)(4)
      has been determined by the use of vibrational spectroscopy. The crystal structure
      consists of isolated [B(3)O(3)(OH)(4)](-) units formed by one tetrahedron and two
      triangles. H bonds and Na atoms link these polyanions to form a three-dimensional
      framework. The Raman spectrum is dominated by an intense band at 1027 cm(-1),
      attributed to BO stretching vibrations of both the trigonal and tetrahedral
      boron. A series of Raman bands at 1213, 1245 and 1281 cm(-1) are ascribed to BOH
      in-plane bending modes. The infrared spectra are characterized by strong overlap
      of broad multiple bands. An intense Raman band found at 620 cm(-1) is attributed
      to the bending modes of trigonal and tetrahedral boron. Multiple Raman bands in
      the OH stretching region are observed at 3206, 3249 and 3385 cm(-1). Raman
      spectroscopy coupled with infrared spectroscopy has enabled aspects about the
      molecular structure of the borate mineral ameghinite to be assessed.

PMID- 22659277
TI  - Excimer formation in inclusion complexes of beta-cyclodextrin with salbutamol,
      sotalol and atenolol: spectral and molecular modeling studies.
AB  - The inclusion complexation behavior of salbutamol, sotalol and atenolol drugs
      with beta-cyclodextrin (beta-CD) were investigated by UV-visible, fluorometry,
      time resolved fluorescence, FT-IR, (1)H NMR, SEM and PM3 methods. The above drugs
      gave a single emission maximum in water where as dual emission in beta-CD. In
      beta-CD solutions the shorter wavelength fluorescence intensity was regularly
      decreased and longer wavelength fluorescence intensity increased. Addition of
      beta-CD to aqueous solutions of drugs resulted into excimer emission. The excimer
      emission is concluded to be due to a 1:2 inclusion complex between beta-CD and
      drug. Nanosecond time-resolved studies indicated that all drugs exhibited
      biexponential decay in solvents and triexponential decay in CD. Investigations of
      thermodynamic and electronic properties confirmed the stability of the inclusion
      complex.

PMID- 22659278
TI  - Response of an environment-sensitive intramolecular charge transfer probe towards
      solubilization of liposome membranes by a non-ionic detergent: association and
      dissociation kinetics.
AB  - The present report describes an endeavor to follow the solubilization of DMPC and
      DMPG liposome membranes by a non-ionic detergent Triton X-100 on the lexicon of
      environment-sensitive intramolecular charge transfer (ICT) photophysics of an
      extrinsic molecular probe 5-(4-dimethylamino-phenyl)-penta-2, 4-dienoic acid
      methyl ester (DPDAME). The prospective applicability of the probe to function as
      a reporter for detergent-sequestered solubilization of liposome membranes is
      argued on the basis of comparison of the spectral properties of the probe in
      various environments. Fluorescence anisotropy study delineates the degree of
      motional restriction imposed on the probe in different microheterogeneous
      assemblies. The kinetics of association of the probe with the liposome membranes
      and the dissociation kinetics of TX-100-sequestered solubilization process of the
      liposomes have been monitored by the stopped-flow fluorescence technique and the
      results are rationalized in relevance to fluorescence anisotropy study.

PMID- 22659279
TI  - Humic and hymatomelanic acids interaction with lanthanide ions.
AB  - The interactions of lanthanide ions, REE(III), with semiquinone radicals
      naturally occurring in humic (HA) and hymatomelanic (HY) acids of different
      origin were studied mainly by EPR spectroscopy. Quantitative EPR analysis proved
      that only the semiquinone free radical concentration in both, HA and HY, was
      affected by interaction with some of the lanthanide ions, whereas the EPR g
      parameters of the formed radical-REE(III) complexes remained unchanged. The
      radical concentration was practically unaffected by the REE(III) ions with 4f(1)
      4f(6) electron configurations and in some degree increased by REE(III) ions with
      4f(8)-4f(14) configuration. The lanthanide playing an exceptional role was
      Gd(III) (4f(7)), which diminished strongly the free radicals concentration. The
      quenching ability of Gd(III) was stronger towards the radicals provided by HA
      than by HY, what was assigned to higher content in HA of both, oxygen-containing
      functional groups and conjugated aromatic rings, leading to more efficient
      Gd(III)-radical interaction. The semiquinone free radicals of HA and HY
      originated from the compost were more reactive than those from peat, as the humic
      acids from mature compost with less bulk density have more accessible functional
      groups.

PMID- 22659280
TI  - Interaction of pyrrolizine derivatives with bovine serum albumin by fluorescence
      and UV-Vis spectroscopy.
AB  - The interaction between pyrrolizine derivatives (PD) and bovine serum albumin
      (BSA) under imitated physiological conditions was analyzed by fluorescence and
      ultraviolet spectra. The experiments were conducted at three different
      temperatures (302, 306 and 310 K) and the results showed that PD caused the
      fluorescence quenching of BSA through a combined quenching procedure. The binding
      constant (K(a)), binding-site number (n) between PD and BSA at different
      temperatures were obtained. According to Forster non-radiation energy transfer
      theory, the binding distance (r) between BSA and PD was calculated. The
      corresponding thermodynamic parameters (DeltaG, DeltaH, and DeltaS) were also
      obtained. The comparison of binding potency of PD and BSA suggested that the
      substituent on the benzene ring could enhance the binding affinity of PD and BSA.
      Finally, we investigated the possible sub-domain on BSA where bind PD by
      displacement experiments.

PMID- 22659281
TI  - A study of molecular structure and vibrational spectra of copper(II) halide
      complex of 2-(2'-thienyl)pyridine.
AB  - In this study, the metal(II) halide of 2-(2'-thienyl)pyridine, (C(9)H(7)NS),
      (with synonym, 2-(2'-pyridyl)thiophene and 2-thiophen-2-ylpyridine), (in
      abbreviated pyth) have been formed by the reaction with copper chloride and was
      formulated as [Cu(pyth)(2)Cl(2)]. The structure and vibrational wavenumbers of
      the formed compound have been calculated by using density functional theory
      (DFT/B3LYP) method with 6-31++G(d,p) and LANL2DZ basis sets in the ground state,
      for the first time. Comparison of the observed IR and micro-Raman fundamental
      frequencies of the mentioned compound and calculated results by density
      functional B3LYP/6-31++G(d,p) and B3LYP/LANL2DZ methods indicates that
      B3LYP/LANL2DZ is superior to the scaled B3LYP/6-31++G(d,p) approach for both
      molecular vibrational modes and optimized geometric parameters of
      [Cu(pyth)(2)Cl(2)] complex. The results of computations exhibit that the copper
      atom is surrounded by N atoms of pyth ligand molecule and Cl atoms.

PMID- 22659282
TI  - Structural and optical characterization of nanosized La(OH)3:Sm3+ phosphor.
AB  - In the present work, Sm(3+) doped La(OH)(3) nano-phosphor (~40 nm) has been
      synthesized using combustion synthesis method and detailed structural and
      spectroscopic characterizations are carried out. On excitation with 532 nm,
      several photoluminescence peaks extending over green to NIR regions have been
      observed and assigned to be due to 4f-4f transitions of Sm(3+) ions. A bright
      orange-red perception is observed in annealed sample, which is 10 times higher
      than as synthesized sample. Time resolved emission spectroscopy reveals
      pronounced effect of heating, which induce good crystalline in the host.

PMID- 22659283
TI  - Zoledronic acid inhibits aromatase activity and phosphorylation: potential
      mechanism for additive zoledronic acid and letrozole drug interaction.
AB  - Zoledronic acid (ZA), a bisphosphonate originally indicated for use in
      osteoporosis, has been reported to exert a direct effect on breast cancer cells,
      although the mechanism of this effect is currently unknown. Data from the ABCSG
      12 and ZO-FAST clinical trials suggest that treatment with the combination of ZA
      and aromatase inhibitors (AI) result in increased disease free survival in breast
      cancer patients over AI alone. To determine whether the mechanism of this
      combination involved inhibition of aromatase, AC-1 cells (MCF-7 human breast
      cancer cells transfected with an aromatase construct) were treated simultaneously
      with combinations of ZA and AI letrozole. This combination significantly
      increased inhibition of aromatase activity of AC-1 cells when compared to
      letrozole alone. Treatment of 1 nM letrozole in combination with 1 MUM or 10 MUM
      ZA resulted in an additive drug interaction on inhibition of cell viability, as
      measured by MTT assay. Treatment with ZA was found to inhibit phosphorylation of
      aromatase on serine residues. Zoledronic acid was also shown to be more effective
      in inhibiting cell viability in aromatase transfected AC-1 cells when compared to
      inhibition of cell viability observed in non-transfected MCF-7. Estradiol was
      able to partially rescue the effect of 1 MUM and 10 MUM ZA on cell viability
      following treatment for 72 h, as shown by a shift to the right in the estradiol
      dose-response curve. In conclusion, these results indicate that the combination
      of ZA and letrozole results in an additive inhibition of cell viability.
      Furthermore, ZA alone can inhibit aromatase activity through inhibition of serine
      phosphorylation events important for aromatase enzymatic activity and contributes
      to inhibition of cell viability.

PMID- 22659284
TI  - Brain-specific promoter/exon I.f of the cyp19a1 (aromatase) gene in Xenopus
      laevis.
AB  - Aromatase, encoded by the cyp19a1 gene, is the key enzyme for estrogen
      biosynthesis. Exon I.f of aromatase transcripts in the Xenopus brain is driven in
      a brain-specific manner. In this study, we cloned brain aromatase with a 5'-end
      of various lengths by 5'-RACE and detected the expression pattern of the
      aromatase mRNA. In Xenopus at the larval stage, the brain aromatase mRNA
      expression was five-fold higher than those in the gonad and liver, and was
      upregulated from stage 42 to stage 50. After isolating the brain-specific
      promoter I.f, which was located ~6.5 kb upstream from gonad-specific exon PII, we
      observed this promoter in a potential cis-elements for several transcriptional
      factors, such as Oct-1, c-Myc, the GATA gene family, C/EBPalpha, Sox5, p300, XFD
      1, AP1, the STAT gene family, FOXD3, and the Smad gene family. In addition, the
      core promoter elements of two initiators and an atypical TATA box were found
      around the 5'-RACE products. In the 5'-flanking region of exon I.f, the binding
      sites for nuclear extracts suggested that the followings are important: the STAT
      gene family, a 38-bp conserved region among five species, FOXD3, and the Smad
      gene family within the region 200 bp upstream from the transcription initiation
      site. Real-time RT-PCR analysis showed that the foxd3, smad2 and smad4.1/4.2
      mRNAs are specifically expressed in the brain. Furthermore, the expression change
      of foxd3, which has been reported as a repressor, indicated that expression
      decreased to stage 50 from stage 42, contrary to that of aromatase mRNA. These
      results may imply that foxd3 expression decreases and aromatase expression
      increases as a result of the contribution to promoter I.f by transcriptional
      activators such as smads. However, since these putative cis-elements and
      transcription initiation sites are not conserved in the brain-specific promoter
      of other species, this transcriptional regulatory mechanism of exon I.f may be
      characteristic of Xenopus.

PMID- 22659285
TI  - On the outdoor annoyance from scooter and motorbike noise in the urban
      environment.
AB  - The health impacts of environmental noise are a growing concern amongst both the
      general public and policy-makers in Europe. Environmental noise - especially from
      road transportation - is widely accepted as an important environmental impact
      factor that can be taken as a start for the process of evaluating the impact of
      annoyance on the exposed urban population. Extensive urbanisation and the
      increase of road transport define the main driving forces for the environmental
      noise exposure of the population. In urban conditions, it is rather common,
      regarding road transportation noise, to hear from people that, especially, PTW
      (Powered Two Wheelers) are annoying, and many times are actually the most
      annoying environmental noise sources introducing a degradation of the urban
      environment. In this research, in Athens city centre, both scooters and
      motorbikes operation patterns are analysed, in the basis of their environmental
      impact through ad-hoc tests to establish if specific features of their emitted
      noise are annoying and affect the quality of life. It resulted that PTW are a
      relevant cause of specific environmental annoyance on pedestrians when low
      background noise levels and sparse traffic flow allow identifying the PTW. Based
      on the results of a measurement campaign, both L(max) and roughness indices are
      identified as characteristic noise signatures of the PTW. Results are compared to
      laboratory studies on annoyance found in literature and to a specific set of
      interviews with a large number of pedestrians in selected sites. Annoyance caused
      by scooters and motorbikes is analysed in the findings and conclusions.

PMID- 22659286
TI  - Adverse effects on sexual development in rat offspring after low dose exposure to
      a mixture of endocrine disrupting pesticides.
AB  - The present study investigated whether a mixture of low doses of five
      environmentally relevant endocrine disrupting pesticides, epoxiconazole,
      mancozeb, prochloraz, tebuconazole and procymidone, would cause adverse
      developmental toxicity effects in rats. In rat dams, a significant increase in
      gestation length was seen, while in male offspring increased nipple retention and
      increased incidence and severity of genital malformations were observed. Severe
      mixture effects on gestation length, nipple retention and genital malformations
      were seen at dose levels where the individual pesticides caused no or smaller
      effects when given alone. Generally, the mixture effect predictions based on dose
      additivity were in good agreement with the observed effects. The results indicate
      that there is a need for modification of risk assessment procedures for
      pesticides, in order to take account of the mixture effects and cumulative
      intake, because of the potentially serious impact of mixed exposure on
      development and reproduction in humans.

PMID- 22659287
TI  - The non-intubated, spontaneously breathing, continuous positive airway pressure
      (CPAP) ventilated pre-term lamb: a unique animal model.
AB  - Neonatologists prefer non-invasive ventilation methods for pre-term neonates, who
      often require surfactant treatment. Therefore, a technology for non-invasive
      surfactant administration would be highly appreciated. We have developed a
      Continuous Powder Aerosolization (CPA) system for the generation of a humidified
      recombinant surfactant protein-C (rSP-C) surfactant aerosol for non-invasive
      administration to pre-term neonates via bi-nasal prongs. Before conducting
      clinical trials, safety testing in an adequate pre-clinical animal model is
      necessary. In contrast to existing pre-term lamb models, this model should use
      non-intubated animals to include upper airways for safety testing. Pre-term
      animals should have already a sufficient respiratory drive to breathe
      spontaneously on non-invasive continuous positive airway pressure (CPAP) support,
      but their lungs should still be pre-mature to be comparable with the clinical
      situation for the treatment of pre-term infants. The aim of this feasibility
      study was therefore to establish a CPAP-stable, non-intubated pre-term lamb model
      for the investigation of safety, efficacy, and pulmonary deposition of a
      humidified rSP-C surfactant aerosol. For this purpose, 19 pre-term lambs with a
      gestational age of 135-137 days (term: about 144 days) were delivered via
      Caesarean section. Four animals died before start of treatment, while the
      remaining animals were treated via customized bi-nasal prongs with rSP-C
      surfactant aerosol or humidified air as vehicle control. To determine pulmonary
      deposition, selected animals received rSP-C surfactant labelled with samarium
      oxide as non-radioactive tracer. Treatment was started at 30 min of age and was
      continued for 1 or 2.5 h. Investigations during the in-life phase included
      observation of clinical signs, haematology, blood gas analysis, and determination
      of minute volume. At 3 h of age, animals were euthanized and organs removed for
      histopathology investigation or for determination of pulmonary deposition.
      Administration of humidified, aerosolized rSP-C surfactant was well tolerated,
      and histopathology investigation of upper airways and lungs revealed no aerosol
      related changes. Mean body weight-corrected pulmonary deposition of rSP-C
      surfactant ranged from 1.7 to 7.7 mg/kg depending on the duration of treatment
      and aerosolization parameters used. A trend towards reduced spontaneous minute
      volumes indicating reduced breathing efforts and towards reduced lung weights
      indicating less fluid in the lungs of surfactant-treated animals compared to
      animals of the vehicle control group could be seen. Taken together, a CPAP
      stable, non-intubated pre-term lamb model was successfully established and the
      parameters for the investigation of safety, efficacy, and pulmonary deposition of
      aerosolized rSP-C surfactant for the subsequent main study were identified.

PMID- 22659288
TI  - Shear stress modulates the expression of the atheroprotective protein Cx37 in
      endothelial cells.
AB  - High laminar shear stress (HLSS) is vasculoprotective partly through induction of
      Kruppel-like factor 2 (KLF2). Connexin37 (Cx37) is highly expressed in
      endothelial cells (ECs) of healthy arteries, but not in ECs overlying
      atherosclerotic lesions. Moreover, Cx37 deletion in apolipoprotein E-deficient
      (ApoE(-/-)) mice increases susceptibility to atherosclerosis. We hypothesized
      that shear stress, through KLF2 modulation, may affect Cx37 expression in ECs.
      Cx37 expression and gap-junctional intercellular (GJIC) dye transfer are
      prominent in the straight portion of carotid arteries of ApoE(-/-) mice, but are
      reduced at the carotid bifurcation, a region subjected to oscillatory flow. Shear
      stress-modifying vascular casts were placed around the common carotid artery of
      ApoE(-/-) mice. Whereas Cx37 expression was conserved in HLSS regions, it was
      downregulated to ~50% in low laminar or oscillatory flow regions. To study the
      mechanisms involved, HUVECs or bEnd.3 cells were exposed to flow in vitro. Cx37
      and KLF2 expression were increased after 24h of HLSS. Interestingly, shear
      dependent Cx37 expression was significantly reduced after silencing of KLF2.
      Moreover after exposure to simvastatin, a well-known KLF2 inducer, KLF2 binds to
      the Cx37 promoter region as shown by ChIP. Finally, GJIC dye transfer was highly
      reduced after KLF2 silencing and was increased after exposure to simvastatin.
      HLSS upregulates the expression of Cx37 in ECs by inducing its transcription
      factor KLF2, which increases intercellular communication. Therefore, this effect
      of shear stress on Cx37 expression may contribute to the synchronization of ECs
      and participate in the protective effect of HLSS.

PMID- 22659289
TI  - Degradation of PCBs in a frankfurter-type meat emulsion: effects of a meat
      starter, its proteins extract and thermal treatments.
AB  - The degradation of a series of polychlorinated biphenyl (PCB) congeners (PCBs 10,
      28, 52, 138, 153, 180) in meat emulsions of a frankfurter type was investigated.
      With a pool of these PCBs added to the meat emulsion, three initial experimental
      groups were used: no further addition, or plus a commercial meat starter
      (containing Staphylococcus xylosus and Staphylococcus carnosus), or plus the
      protein extract from this commercial meat starter. Prior to further treatments,
      these samples were incubated for 72 h at 4 degrees C. These meat emulsions were
      then either left at 4  degrees C (raw) or thermally treated to two different
      internal temperatures: 78 and 100  degrees C. Following cooling and a further 24
      h at 4  degrees C, all of the samples were extracted with hexane to recover the
      PCB residues, following method EPA 608, with some modifications. The addition
      into the meat emulsion of the commercial meat starter and the proteins extract
      both affected PCB degradation. Also, the effects of thermal treatment at both
      temperatures saw the PCB contents successfully reduced, as compared to the raw
      meat emulsions.

PMID- 22659290
TI  - A caveolin-binding domain in the HCN4 channels mediates functional interaction
      with caveolin proteins.
AB  - Pacemaker (HCN) channels have a key role in the generation and modulation of
      spontaneous activity of sinoatrial node myocytes. Previous work has shown that
      compartmentation of HCN4 pacemaker channels within caveolae regulates important
      functions, but the molecular mechanism responsible is still unknown. HCN channels
      have a conserved caveolin-binding domain (CBD) composed of three aromatic amino
      acids at the N-terminus; we sought to evaluate the role of this CBD in channel
      protein interaction by mutational analysis. We generated two HCN4 mutants with a
      disrupted CBD (Y259S, F262V) and two with conservative mutations (Y259F, F262Y).
      In CHO cells expressing endogenous caveolin-1 (cav-1), alteration of the CBD
      shifted channels activation to more positive potentials, slowed deactivation and
      made Y259S and F262V mutants insensitive to cholesterol depletion-induced
      caveolar disorganization. CBD alteration also caused a significant decrease of
      current density, due to a weaker HCN4-cav-1 interaction and accumulation of
      cytoplasmic channels. These effects were absent in mutants with a preserved CBD.
      In caveolin-1-free fibroblasts, HCN4 trafficking was impaired and current density
      reduced with all constructs; the activation curve of F262V was not altered
      relative to wt, and that of Y259S displayed only half the shift than in CHO
      cells. The conserved CBD present in all HCN isoforms mediates their functional
      interaction with caveolins. The elucidation of the molecular details of HCN4-cav
      1 interaction can provide novel information to understand the basis of cardiac
      phenotypes associated with some forms of caveolinopathies.

PMID- 22659291
TI  - Ischemia-reperfusion induces myocardial infarction through mitochondrial Ca2+
      overload.
AB  - Both mitochondria and the sarcoplasmic reticulum (SR) are essential for
      myocardial homeostasis and control of cardiac function. Uptake of Ca(2+) from the
      cytosol into SR is mediated by the Ca(2+)-dependent ATPase SERCA2a, which is
      reversibly inhibited by phospholamban (PLN). We previously showed that removal of
      PLN inhibition of SERCA2a with an antibody to (anti-) PLN reduces cytosolic
      Ca(2+) overload, thereby attenuating the spread of contraction bands and fodrin
      proteolysis, during reperfusion after cardiac ischemia. We have now examined the
      effects of anti-PLN injection into the heart on the development of myocardial
      infarction (MI) after ischemia-reperfusion in rats. Whereas anti-PLN injection
      attenuated cytosolic Ca(2+) overload, it did not affect MI size 6h after the
      onset of reperfusion and actually increased it at 30 min. The antibody also
      increased the release of apoptosis-inducing factor (AIF) from mitochondria into
      the cytosol, indicative of enhanced opening of the mitochondrial permeability
      transition pore (mPTP). Administration of an mPTP blocker at the time of
      reperfusion or of a blocker of the mitochondrial Ca(2+) uniporter significantly
      suppressed the release of AIF and the development of MI. These results indicate
      that the enhancement of SR Ca(2+) loading by anti-PLN injection facilitated
      Ca(2+) uniporter-dependent mitochondrial Ca(2+) uptake and thereby induced mPTP
      opening and MI development during early reperfusion. The enhancement of SR Ca(2+)
      loading thus aggravates MI in a manner independent of cytosolic Ca(2+) overload.
      Given that cytosolic Ca(2+) overload induces contraction bands, our findings are
      inconsistent with a causal relation between contraction bands and MI.

PMID- 22659292
TI  - Severe peritonitis induced by methotrexate during treatment of persistent
      gestational trophoblastic disease.

PMID- 22659294
TI  - Is supersize more than just too much food?

PMID- 22659293
TI  - The intersection of neurotoxicology and endocrine disruption.
AB  - Endocrine disruption, the guiding theme of the 27th International Neurotoxicology
      Conference, merged into the neurotoxicology agenda largely because hormones help
      steer the process of brain development. Although the disruption motif first
      attracted public health attention because of reproductive anomalies in both
      wildlife and humans, the neurobehavioral implications had been planted decades
      earlier. They stemmed from the principle that sex differences in behavior are
      primarily the outcomes of differences in how the brain is sexually differentiated
      during early development by gonadal hormones (the Organizational Hypothesis). We
      also now understand that environmental chemicals are capable of altering these
      underlying events and processes. Among those chemicals, the group labeled as
      endocrine disrupting chemicals (EDCs) offers the clearest evidence of such
      selectivity, a consequence of their actions on the endogenous sex steroids,
      androgens and estrogens. Two EDCs in particular offer useful and intriguing
      examples. One is phthalate esters. The other is bisphenol A. Both agents are used
      extensively in plastics manufacture, and are pervasive in the environment. Both
      are produced in immense quantities. Both are found in almost all humans.
      Phthalates are considered to function in essence as anti-androgens, while
      bisphenol A is labeled as an estrogen. Their associations with brain sexual
      differentiation are reviewed and further questions noted. Both EDCs produce a
      wider spectrum of health effects, however, than would be extrapolated simply from
      their properties as anti-androgens and estrogens. Obesity is one example. Further
      complicating their assessment as health risks are questions about nonmonotonic
      dose-response functions and about transgenerational effects incurred via
      epigenetic mechanisms. All these facets of endocrine disruption are pieces of a
      puzzle that challenge neurotoxicologists for solutions.

PMID- 22659295
TI  - Short peptides derived from the interaction domain of SARS coronavirus
      nonstructural protein nsp10 can suppress the 2'-O-methyltransferase activity of
      nsp10/nsp16 complex.
AB  - Coronaviruses are the etiological agents of respiratory and enteric diseases in
      humans and livestock, exemplified by the life-threatening severe acute
      respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV). However,
      effective means for combating coronaviruses are still lacking. The interaction
      between nonstructural protein (nsp) 10 and nsp16 has been demonstrated and the
      crystal structure of SARS-CoV nsp16/10 complex has been revealed. As nsp10 acts
      as an essential trigger to activate the 2'-O-methyltransferase activity of nsp16,
      short peptides derived from nsp10 may have inhibitory effect on viral 2'-O
      methyltransferase activity. In this study, we revealed that the domain of aa 65
      107 of nsp10 was sufficient for its interaction with nsp16 and the region of aa
      42-120 in nsp10, which is larger than the interaction domain, was needed for
      stimulating the nsp16 2'-O-methyltransferase activity. We further showed that two
      short peptides derived from the interaction domain of nsp10 could inhibit the 2'
      O-methyltransferase activity of SARS-CoV nsp16/10 complex, thus providing a novel
      strategy and proof-of-principle study for developing peptide inhibitors against
      SARS-CoV.

PMID- 22659296
TI  - Biochemical characterization of the small hydrophobic protein of avian
      metapneumovirus.
AB  - Avian metapneumovirus (AMPV) is a paramyxovirus that has three membrane proteins
      (G, F, and SH). Among them, the SH protein is a small type II integral membrane
      protein that is incorporated into virions and is only present in certain
      paramyxoviruses. In the present study, we show that the AMPV SH protein is
      modified by N-linked glycans and can be released into the extracellular
      environment. Furthermore, we demonstrate that glycosylated AMPV SH proteins form
      homodimers through cysteine-mediated disulfide bonds, which has not been reported
      previously for SH proteins of paramyxoviruses.

PMID- 22659297
TI  - Complete genomic characterization of two tick-borne encephalitis viruses isolated
      from China.
AB  - Tick-borne encephalitis (TBEV) is prevalent over a wide area of the Eurasian
      continent. TBE viruses cause severe encephalitis in humans, with serious
      sequelae, and have a significant impact on public health in these endemic
      regions. To gain insight into genetic evolution of tick-borne encephalitis virus
      (TBEV) in China, the complete genomic sequences of two TBEV strains Senzhang and
      MDJ01, which were isolated in 1953 and 2001 respectively, were characterized. The
      complete genome sequences of two strains were all consist 10,784 nucleotides and
      there are 364 nucleotides deletion in the 3' nontranslated region. Compared with
      other TBEV strains, homology range from 85.2% (Zausaev) to 99.6% (MDJ02 and
      MDJ03) on the level of nucleotide. Phylogenetic trees based on the complete
      genome, open reading frame and E gene nucleotide sequences all showed that the
      strains Senzhang and MDJ01 belong to Far-Eastern subtype and cluster with other
      Chinese TBEV strains. All these implied that TBEVs prevalent in China were highly
      conservative, other measurement should be taken to improve protective efficacy of
      present vaccine.

PMID- 22659298
TI  - Altered microRNA expression in B lymphocytes in multiple sclerosis: towards a
      better understanding of treatment effects.
AB  - MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. We
      compared the expression of 1059 miRNAs in B lymphocytes from untreated and
      natalizumab treated relapsing-remitting multiple sclerosis (RRMS) patients and
      healthy volunteers (HV). Forty nine miRNAs were down-regulated in untreated MS
      patients compared with HV. A distinct pattern of 10 differentially expressed
      miRNAs was found in natalizumab treated patients compared with untreated
      patients. Two clusters, i.e. miR-106b-25 and miR-17-92, were particularly
      deregulated. MiRNA-mRNA interaction analysis revealed B cell receptor,
      phosphatidyl-inositol-3-kinase (PI3K) and phosphatase and tensin homology (PTEN)
      signaling being the key affected pathways. We discovered deregulated viral miRNAs
      in untreated patients as compared with HV and natalizumab treated patients, a
      novel finding that may be related to latency and activation of viruses in MS. Our
      findings provide first insights into miRNA dependent regulation of B cell
      function in MS and the impact of a therapy not primarily targeting B cells on
      this regulation.

PMID- 22659299
TI  - Lipids and vesicular transport.

PMID- 22659301
TI  - A novel non-synonymous SNP of the COLX gene and its association with duck
      reproductive traits.
AB  - Type X collagen (COLX) is a known marker of chondrocyte hypertrophy, which is
      exclusively expressed in hypertrophic chondrocytes and is reported to be involved
      in the process of mineralization. The purpose of this study was to investigate
      the relationship between COLX genotypes of single nucleotide polymorphism (SNP)
      and reproductive traits of Tsaiya ducks. A total of 336 Brown Tsaiya ducks from
      two lines, the control line (CL) with no selection and the selected line (SL),
      were employed for testing. We employed polymerase chain reaction -single strand
      conformation polymorphism and DNA sequencing to screen the polymorphisms of the
      COLX gene. One novel non-synonymous SNP in coding region (T74C: Val24Ala) of the
      COLX gene was found, and resulted in 3 genotypes TT, TC, and CC. The frequencies
      of genotype TT and allele T were high in both lines. Regarding egg weight at 40
      weeks of age (EW40), based on SNP-trait association analysis, ducks with the CC
      genotype had a 4.09 and 4.15 g/egg lower EW40 as compared with ducks with the TT
      and TC genotypes in the CL, respectively (P < 0.05). In addition, significant
      positive dominance effect of 2.10 +/- 1.05 g/egg for EW40 was detected (P =
      0.0481). This finding indicated that selection for the genotype TT and TC ducks
      might contribute to an improved egg weight in the Tsaiya ducks. Further
      investigations on more duck populations with large sample sizes are needed to
      confirm.

PMID- 22659300
TI  - Neuronal porosome proteome: Molecular dynamics and architecture.
AB  - Porosomes are the universal secretory portals at the cell plasma membrane, where
      membrane-bound secretory vesicles transiently dock and fuse to expel
      intravesicular contents to the outside during cell secretion. In the past decade,
      the neuronal porosome complex, a 10-15nm cup-shaped lipoprotein structure has
      been isolated, its partial composition and 3D contour map determined, and it has
      been functionally reconstituted into artificial lipid membrane. Here we further
      determine the composition of the neuronal porosome proteome using immunoisolation
      and gel filtration chromatography, followed by tandem mass spectrometry. Results
      from the study demonstrate nearly 40 proteins to constitute the neuronal porosome
      proteome. Furthermore, interaction of proteins within the porosome and their
      resulting arrangement is predicted. The association and dissociation of proteins
      at the porosome following stimulation of cell secretion demonstrate the dynamic
      nature of the organelle.

PMID- 22659302
TI  - Dysregulated dopamine storage increases the vulnerability to alpha-synuclein in
      nigral neurons.
AB  - Impairments in the capacity of dopaminergic neurons to handle cytoplasmic
      dopamine may be a critical factor underlying the selective vulnerability of
      midbrain dopamine neurons in Parkinson's disease. Furthermore, toxicity of alpha
      synuclein in dopaminergic neurons has been suggested to be mediated by direct
      interaction between dopamine and alpha-synuclein through formation of abnormal
      alpha-synuclein species, although direct in vivo evidence to support this
      hypothesis is lacking. Here, we investigated the role of dopamine availability on
      alpha-synuclein mediated neurodegeneration in vivo. We found that overexpression
      of alpha-synuclein in nigral dopamine neurons in mice with deficient vesicular
      storage of dopamine led to a significant increase in dopaminergic
      neurodegeneration. Importantly, silencing the tyrosine hydroxylase enzyme -
      thereby reducing dopamine content in the nigral neurons - reversed the increased
      vulnerability back to the baseline level observed in wild-type littermates, but
      failed to eliminate it completely. Importantly, TH knockdown was not effective in
      altering the toxicity in the wild-type animals. Taken together, our data suggest
      that under normal circumstances, in healthy dopamine neurons, cytoplasmic
      dopamine is tightly controlled such that it does not contribute significantly to
      alpha-synuclein mediated toxicity. Dysregulation of the dopamine machinery in the
      substantia nigra, on the other hand, could act as a trigger for induction of
      increased toxicity in these neurons and could explain how these neurons become
      more vulnerable and die in the disease process.

PMID- 22659303
TI  - Predictive neural biomarkers of clinical response in depression: a meta-analysis
      of functional and structural neuroimaging studies of pharmacological and
      psychological therapies.
AB  - We performed a systematic review and meta-analysis of neural predictors of
      response to the most commonly used, evidence based treatments in clinical
      practice, namely pharmacological and psychological therapies. Investigations of
      medication-free subjects suffering from a current major depressive episode who
      underwent positron emission tomography (PET) or functional or structural magnetic
      resonance imaging (MRI) scans prior to the initiation of treatment were reviewed.
      Results of 20 studies from 15 independent samples were included in the functional
      imaging meta-analysis and 9 studies from 6 independent samples in the structural
      neuroimaging meta-analysis. Regional activations with prognostic value include
      the well replicated finding that increased baseline activity in the anterior
      cingulate is predictive of a higher likelihood of improvement. As well, increased
      baseline activation in the insula and striatum is associated with higher
      likelihood of a poorer clinical response. Structural neuroimaging studies
      indicated that a decrease in right hippocampal volume is a statistically
      significant predictor of poorer treatment response. Overall, the predictive
      information that is measurable with brain imaging techniques is both multimodal
      and regionally distributed as it contains functional as well as structural
      correlates which encompass several brain regions within a frontostriatal-limbic
      network. To develop clinically relevant, prognostic markers will require high
      predictive accuracy at the level of the individual. Predicting clinical response
      will help to stratify patients and to identify at an early stage those patients
      who may require more intensive or combined therapies. We propose that structural
      and functional neuroimaging show significant potential for the development of
      prognostic markers of clinical response in the treatment of depression.

PMID- 22659306
TI  - Unmasking adenosine 2A receptors (A2ARs) in monkey basal ganglia output neurons
      using cholera toxin subunit B (CTB).
AB  - The A(2A)R has become a therapeutic target in Parkinson disease due to its
      functional role in the striatum, capable of modulating dopaminergic
      neurotransmission in the basal ganglia. No conclusive evidence, however, has been
      provided to demonstrate the existence of A(2A)Rs in the output nuclei of the
      basal ganglia: the internal segment of the globus pallidus (GPi) and substantia
      nigra pars reticulata (SNr). Using immunohistochemistry and in situ hybridization
      techniques we have confirmed the presence of A(2A)Rs in both the striatum (medium
      spiny and cholinergic neurons) and the external segment of the globus pallidus
      (GPe), in the monkey. The antibody routinely used to label A(2A)Rs failed to
      detect A(2A)R-positive neurons in the GPi and SNr, however, in situ hybridization
      showed that A(2A)R mRNA transcripts were indeed present in both these nuclei.
      Surprisingly, by labeling pallidothalamic and nigrothalamic projection neurons
      originating in the GPi and SNr with the neuronal retrograde tracer cholera toxin
      subunit B (CTB), the receptor protein was unmasked and detectable using the
      antibody. This unmasking of the protein was specific to CTB and not an artifact
      of the tracer. We have shown unequivocally that the A(2A)R is present in the
      output nuclei of the primate basal ganglia, however, to be able to detect the
      receptor immunohistochemically, unmasking the protein with CTB was necessary. The
      presence of A(2A)Rs in the GPi and SNr suggests that these output nuclei could be
      targeted therapeutically in Parkinson disease to restore abnormal activity in the
      basal ganglia.

PMID- 22659305
TI  - Evidence for astrocytes as a potential source of the glutamate excess in temporal
      lobe epilepsy.
AB  - Increased extracellular brain glutamate has been implicated in the
      pathophysiology of human refractory temporal lobe epilepsy (TLE), but the cause
      of the excessive glutamate is unknown. Prior studies by us and others have shown
      that the glutamate degrading enzyme glutamine synthetase (GS) is deficient in
      astrocytes in the epileptogenic hippocampal formation in a subset of patients
      with TLE. We have postulated that the loss of GS in TLE leads to increased
      glutamate in astrocytes with elevated concentrations of extracellular glutamate
      and recurrent seizures as the ultimate end-points. Here we test the hypothesis
      that the deficiency in GS leads to increased glutamate in astrocytes. Rats were
      chronically infused with methionine sulfoximine (MSO, n=4) into the hippocampal
      formation to induce GS deficiency and recurrent seizures. A separate group of
      rats was infused with 0.9% NaCl (saline) as a control (n=6). At least 10days
      after the start of infusion, once recurrent seizures were established in the MSO
      treated rats, the concentration of glutamate was assessed in CA1 of the
      hippocampal formation by immunogold electron microscopy. The concentration of
      glutamate was 47% higher in astrocytes in the MSO-treated vs. saline-treated rats
      (p=0.02), and the ratio of glutamate in astrocytes relative to axon terminals was
      increased by 74% in the MSO-treated rats (p=0.003). These data support our
      hypothesis that a deficiency in GS leads to increased glutamate in astrocytes. We
      additionally propose that the GS-deficient astrocytes in the hippocampal
      formation in TLE lead to elevated extracellular brain glutamate either through
      decreased clearance of extracellular glutamate or excessive release of glutamate
      into the extracellular space from these cells, or a combination of the two.

PMID- 22659307
TI  - Wide therapeutic time-window of low-frequency stimulation at the subiculum for
      temporal lobe epilepsy treatment in rats.
AB  - Low-frequency stimulation (LFS) has been considered as an option for the
      treatment of intractable epilepsy. However, previous data showed that LFS of
      certain brain regions only exerts its effect within a very narrow therapeutic
      time window, which lasts from seconds to tens of seconds, thus restricting its
      clinical application. The present study was designed to determine whether there
      exists a target with a wider therapeutic window for LFS treatment. Therefore,
      evoked seizures in the rat were induced by amygdala kindling and spontaneous
      seizures were induced by pilocarpine. The effects of different modes of LFS at
      the subiculum on the progression and severity of evoked seizures and the
      frequency of spontaneous seizure were evaluated. We found that (i) LFS at 1Hz
      delivered to the subiculum before and immediately after the kindling
      stimulations, or after the cessation of afterdischarge (afterdischarge duration,
      ADD) decreased the seizure stages and shortened the ADD both in seizure
      acquisition and expression in amygdaloid-kindled seizures. In addition, even LFS
      delivered after duration of double the ADD prolonged the kindling progression.
      (ii) LFS delivered at 1Hz, but not 0.5, 3 or 130Hz, immediately after the
      cessation of kindling stimulations retarded the progression of kindling seizures.
      (iii) Pilocarpine-induced spontaneous seizures were completely inhibited by 1Hz
      LFS. Thus, these results demonstrated that LFS of the subiculum has a wide
      therapeutic time-window for temporal lobe epilepsy treatment in rats, suggesting
      that the subiculum may be a promising and suitable target for clinical
      application.

PMID- 22659304
TI  - Neurogenetics of depression: a focus on reward processing and stress sensitivity.
AB  - Major depressive disorder (MDD) is etiologically complex and has a heterogeneous
      presentation. This heterogeneity hinders the ability of molecular genetic
      research to reliably detect the small effects conferred by common genetic
      variation. As a result, significant research efforts have been directed at
      investigating more homogenous intermediate phenotypes believed to be more
      proximal to gene function and lie between genes and/or environmental effects and
      disease processes. In the current review we survey and integrate research on two
      promising intermediate phenotypes linked to depression: reward processing and
      stress sensitivity. A synthesis of this burgeoning literature indicates that a
      molecular genetic approach focused on intermediate phenotypes holds significant
      promise to fundamentally improve our understanding of the pathophysiology and
      etiology of depression, which will be required for improved diagnostic
      definitions and the development of novel and more efficacious treatment and
      prevention strategies. We conclude by highlighting challenges facing intermediate
      phenotype research and future development that will be required to propel this
      pivotal research into new directions.

PMID- 22659309
TI  - Local application of gentamicin-containing collagen implant in the prophylaxis
      and treatment of surgical site infection following cardiac surgery.
AB  - BACKGROUND: For the cardiac surgeon and patient the development of sternal wound
      infection is a serious post-operative complication associated with increased risk
      of death and also considerable morbidity. METHODS: Nine publications were
      identified using the PubMed online database and search terms 'gentamicin
      containing collagen implant' plus 'surgical site infection', 'wound infection'
      and 'cardiac surgery'. RESULTS: Six out of eight studies demonstrated that
      prophylactic use of gentamicin-containing collagen implants (GCCI) significantly
      reduce the wound infection rate following cardiac surgery (via sternotomy)
      compared to standard treatment alone. The adjunctive use of GCCI is particularly
      beneficial in high-risk subjects e.g. diabetes and obese patients. GCCI
      significantly improve the morbidity associated with SSI following cardiac surgery
      by shortening the recovery phase and length of hospital stay; reducing the need
      for surgical revision and use of antibiotics. GCCI have been shown to be cost
      saving across a wide spectrum of patients. A further study has shown that GCCI
      may also have a therapeutic role to play in patients with deep sternal wounds.
      CONCLUSION: This review demonstrates that when used dry prior to insertion GCCI
      can be effective in reducing the rate of SSI following cardiac surgery. GCCI have
      also been shown to be cost saving as they reduce the substantial morbidity
      associated with deep SSI. The adjunctive use of GCCI is particularly beneficial
      in high-risk patients. GCCI may also have a role to play in the treatment of deep
      sternal wound infection.

PMID- 22659308
TI  - Functional analysis of dopaminergic systems in a DYT1 knock-in mouse model of
      dystonia.
AB  - The dystonias are a group of disorders characterized by involuntary twisting
      movements and abnormal posturing. The most common of the inherited dystonias is
      DYT1 dystonia, which is due to deletion of a single GAG codon (DeltaE) in the
      TOR1A gene that encodes torsinA. Since some forms of dystonia have been linked
      with dysfunction of brain dopamine pathways, the integrity of these pathways was
      explored in a knock-in mouse model of DYT1 dystonia. In DYT1(DeltaE) knock-in
      mice, neurochemical measures revealed only small changes in the content of
      dopamine or its metabolites in tissue homogenates from caudoputamen or midbrain,
      but microdialysis studies revealed robust decreases in baseline and amphetamine
      stimulated extracellular dopamine in the caudoputamen. Quantitative stereological
      methods revealed no evidence for striatal or midbrain atrophy, but substantia
      nigra neurons immunopositive for tyrosine hydroxylase were slightly reduced in
      numbers and enlarged in size. Behavioral studies revealed subtle abnormalities in
      gross motor activity and motor coordination without overt dystonia.
      Neuropharmacological challenges of dopamine systems revealed normal behavioral
      responses to amphetamine and a minor increase in sensitivity to haloperidol.
      These results demonstrate that this DYT1(DeltaE) knock-in mouse model of dystonia
      harbors neurochemical and structural changes of the dopamine pathways, as well as
      motor abnormalities.

PMID- 22659310
TI  - Accuracy of FAST scan in blunt abdominal trauma in a major London trauma centre.
AB  - INTRODUCTION: Blunt abdominal trauma (BAT) is a leading cause of morbidity and
      mortality. Rapid diagnosis and treatment with the Advanced Trauma Life Support
      guidelines are vital, leading to the development of Focused Assessment with
      Sonography in Trauma (FAST). METHODS: A retrospective study carried out from
      January 2007-2008 on all patients who presented with BAT and underwent FAST scan.
      All patients subsequently had a CT scan within 2 h of admission or a laparotomy
      within two days. The presence of intra-peritoneal free fluid was interpreted as
      positive. RESULTS: 100 patients with BAT presented; 71 had complete data. The
      accuracy of FAST in BAT was 59.2%; in these 31 (43.7%) were confirmed by CT and
      11 (15%) by laparotomy. There were 29 (40.8%) inaccurate FAST scans, all
      confirmed by CT. FAST had a specificity of 94.7% (95% CI: 0.75-0.99) and
      sensitivity of 46.2% (95% CI: 0.33-0.60). Positive Predictive Value of 0.96 (0.81
      0.99) and Negative Predictive Value of 0.39 (0.26-0.54). Fisher's exact test
      shows positive FAST is significantly associated with Intra-abdominal pathology
      (p=0.001). Cohen's chance corrected agreement was 0.3. 21 out of 28 who underwent
      laparotomies had positive FAST results indicating accuracy of 75% (95% CI: 57%
      87%). CONCLUSION: Patients with false negative scans, requiring therapeutic
      laparotomy is concerning. In unstable patients FAST may help in triaging and
      identifying those requiring laparotomy. Negative FAST scans do not exclude
      abdominal injury. Further randomised control trials are recommended if the role
      of FAST is to be better understood.

PMID- 22659311
TI  - Local application of gentamicin-containing collagen implant in the prophylaxis
      and treatment of surgical site infection in orthopaedic surgery.
AB  - BACKGROUND: There is still significant risk of patients developing surgical site
      infection (SSI) following orthopaedic surgery due to growing demand for joint
      surgery in high-risk patients and increasing complexity of procedures. The higher
      rate of SSI seen in high-risk procedures and also in high-risk patients is of
      concern as the development of infection can be a very serious complication of
      orthopaedic surgery and has implications for patient morbidity, length of
      hospital stay (LOS), resource utilisation and healthcare costs. This article
      provides an overview of the efficacy of prophylactic and therapeutic application
      of resorbable gentamicin-containing collagen implants (GCCI) in the prevention of
      SSI following orthopaedic surgical procedures. METHOD: Thirteen publications were
      identified using the PubMed online database and search terms 'gentamicin
      containing collagen implant' plus 'orthopaedic surgery', 'osteomyelitis',
      'osteitis', 'amputation', 'surgical site infection' and 'wound infection'.
      RESULTS: Five studies have demonstrated that prophylactic use of GCCI can reduce
      the wound infection rate in orthopaedic surgical procedures ranging from
      discectomy to amputation in patients with diabetes. Eight studies have
      demonstrated that GCCI may also have a role to play in treating both acute and
      chronic osteomyelitis. CONCLUSION: This review demonstrates that prophylactic use
      of GCCI can have a positive effect on wound healing in a range of orthopaedic
      surgical procedures and in high-risk patients. GCCI may also have a role to play
      in the treatment of osteomyelitis.

PMID- 22659312
TI  - Local application of gentamicin-containing collagen implant in the prophylaxis
      and treatment of surgical site infection.

PMID- 22659313
TI  - The effect of centralisation on the outcomes of oesophagogastric surgery--a
      fifteen year audit.
AB  - INTRODUCTION: Centralisation of oesophagogastric (OG) resectional services has
      been proposed to improve patient outcomes in terms of perioperative mortality and
      long-term survival. Centralisation of services occurred in Gloucester 5 years
      ago. The aim of this paper is to assess if local patient outcomes have benefited
      from centralisation. METHODS: All oesophagogastric resections performed in our
      unit over a 15-year period (10-years pre-centralisation and 5-years post
      centralisation) were assessed retrospectively. Patient demographics, pathological
      details and date of death were identified. Perioperative mortality (30 and 90
      day) and estimated Kaplan-Meier survival was compared for cases performed pre-
      and post-centralisation of services. RESULTS: 456 resections for cancer were
      performed in the 15-year period; 234 of these were performed pre-centralisation
      (mean 23.4, range 13-31) and 222 were performed post-centralisation (mean 44.4,
      range 40-50). Median survival rates for gastric cancer were 1.1 years pre
      centralisation and 1.5 years post-centralisation (p = 0.147) and median survival
      for oesophageal cancer improved from 1.1 years to 2.1 respectively (p = 0.028).
      Combined OG 30-day mortality rates improved from 10.3% pre-centralisation to 3.6%
      post-centralisation (p = 0.006, Fisher's exact test). DISCUSSION: Centralisation
      of OG services in Gloucester has resulted in twice as many resections being
      performed locally. Median survival for patients with oesophageal cancer has
      increased by 1 year and the 30-day mortality rate following resection has reduced
      by almost two thirds. Although other factors (such as improvements in oncological
      treatments, staging and critical care management over the 15-year time period)
      have undoubtedly had roles to play in these improvements, the results of this
      study support the policy of centralisation of upper GI cancer services.

PMID- 22659314
TI  - A ratiometric fluorescent probe for assessing mitochondrial phospholipid
      peroxidation within living cells.
AB  - Mitochondrial oxidative damage contributes to a wide range of pathologies, and
      lipid peroxidation of the mitochondrial inner membrane is a major component of
      this disruption. However, despite its importance, there are no methods to assess
      mitochondrial lipid peroxidation within cells specifically. To address this unmet
      need we have developed a ratiometric, fluorescent, mitochondria-targeted lipid
      peroxidation probe, MitoPerOx. This compound is derived from the C11
      BODIPY(581/591) probe, which contains a boron dipyromethane difluoride (BODIPY)
      fluorophore conjugated via a dienyl link to a phenyl group. In response to lipid
      peroxidation the fluorescence emission maximum shifts from ~590 to ~520nm. To
      target this probe to the matrix-facing surface of the mitochondrial inner
      membrane we attached a triphenylphosphonium lipophilic cation, which leads to its
      selective uptake into mitochondria in cells, driven by the mitochondrial membrane
      potential. Here we report on the development and characterization of MitoPerOx.
      We found that MitoPerOx was taken up very rapidly into mitochondria within cells,
      where it responded to changes in mitochondrial lipid peroxidation that could be
      measured by fluorimetry, confocal microscopy, and epifluorescence live cell
      imaging. Importantly, the peroxidation-sensitive change in fluorescence at 520nm
      relative to that at 590nm enabled the use of the probe as a ratiometric
      fluorescent probe, greatly facilitating assessment of mitochondrial lipid
      peroxidation in cells.

PMID- 22659315
TI  - Determination of phospholipase activity of PAF acetylhydrolase.
AB  - This article presents a radiometric assay to determine the enzymatic activity of
      platelet-activating factor (PAF) acetylhydrolase (PAF-AH), also known as
      lipoprotein-associated phospholipase A2 and phospholipase A2 group 7A. The method
      is based on the release of radioactively labeled acetate from sn-2-labeled PAF
      and separation of substrate and product using reversed-phase column
      chromatography on octadecyl silica gel cartridges. The assay is fast, convenient,
      reproducible, sensitive, and inexpensive. The instrumentation required includes
      standard laboratory equipment and a liquid scintillation counter. The assay is
      also useful to determine the activity of intracellular PAF-AH (PAF-AH II),
      provided that a few modifications are included. The enzymatic activity determined
      using PAF as the substrate is a direct indication of the ability of plasma
      samples, purified preparations, and cellular and tissue lysates to hydrolyze
      short- and medium-chain phospholipids that may or may not harbor oxidized
      functionalities. In addition, the assay can be used to test the suitability of
      other phospholipids, including species containing oxidized, long-chain sn-2 fatty
      acyl groups, as PAF-AH substrates. This versatile assay can be used to accurately
      determine PAF-AH activity in biological samples and preliminarily assess affinity
      and efficiency of the hydrolysis of potential substrates present in complex
      mixtures.

PMID- 22659316
TI  - Atherogenic and pulmonary responses of ApoE- and LDL receptor-deficient mice to
      sidestream cigarette smoke.
AB  - Plasma lipoproteins play important roles in the development and progression of
      atherosclerosis. Two widely used mouse models of experimental atherosclerosis,
      apolipoprotein E-deficient (ApoE -/-) and LDL receptor-deficient (LDLr -/-) mice,
      have major differences in lipoprotein characteristics. These include differences
      in lipoprotein cholesterol distribution, lipoprotein compositions, apoliporoteins
      distribution, and susceptibility to oxidation. In the present study, we compared
      pulmonary and cardiovascular responses of ApoE -/- and LDLr -/- mice to
      sidestream cigarette smoke (SSCS) exposure to determine if strain differences
      influence their predisposition to SSCS-mediated promotion of atherosclerosis.
      Female ApoE -/- and LDLr -/- mice were maintained on a saturated fat enriched
      diet and exposed to SSCS in whole body exposure chambers for 15 weeks (4h/day, 5
      days/week). At terminations, the levels of pulmonary injury markers in
      bronchoalveolar lavage (BAL) fluids from 6 mice per group and atherosclerotic
      lesion formation in 14 mice per group were analyzed. Total BAL cells and
      polymorphonuclear leukocytes were not significantly altered by SSCS exposure in
      both mouse models. Total protein, LDH, and cytokine concentrations in cell-free
      BAL fluids were also not significantly affected by chronic SSCS exposure in
      either mouse strain. SSCS significantly reduced surfactant protein D levels in
      both strains to a similar extent. However, SSCS exposure increased significantly
      the percent atherosclerotic lesion areas covering aortic intimal surfaces of ApoE
      -/- (control-25.3+/-1.52 vs. SSCS-31.9+/-2.02, p=0.012) as well as in LDLr -/-
      (control-30.97+/-1.1 vs. SSCS-36.61+/-1.7, p=0.028) mice. In contrast, the serum
      cholesterol concentrations of SSCS-exposed ApoE -/- mice were similar to that of
      controls (control-1255+/-85 vs. SSCS-1190+/-61mg/dl, p=0.552) but increased
      significantly in SSCS-exposed LDLr -/- mice (control-998+/-114 vs. SSCS-1577+/
      142mg/dl, p=0.008). These results showing different effects of identical SSCS
      exposure on plasma cholesterol concentrations in these two mouse models suggest a
      role of multiple mechanisms in SSCS-induced atherosclerosis.

PMID- 22659318
TI  - Cadmium-induced apoptosis in the BJAB human B cell line: involvement of
      PKC/ERK1/2/JNK signaling pathways in HO-1 expression.
AB  - Heme oxygenase-1 (HO-1, EC 1.14.99.3) is a key enzyme in the cellular response to
      tissue injury and oxidative stress. It oxidizes heme, a pro-oxidant and toxic
      species, to biliverdin, CO, and free iron. Cytoprotection during the heat shock
      response is a complex phenomenon involving multiple inducible mechanisms. Several
      important pathways involving serine/threonine kinases mediate the induction of HO
      1 in response to external stimuli. The objective of the present study was to
      investigate the mechanism of HO-1 induction during cadmium (Cd)-induced oxidative
      stress and apoptosis in the lymphocyte B cell line BJAB. To examine the signal
      pathways involved in HO-1 expression, cells were pre-treated with various
      inhibitors of key signaling molecules. Increased DNA fragmentation and caspase-3
      activity were observed in BJAB cells exposed to 5-40 MUM CdCl(2) revealing that
      Cd induced apoptosis in these cells. Our results indicate that Cd also induces HO
      1 expression which is modulated by the thiol redox status, tyrosine kinase and
      PI3-kinase. The inhibitory effect of calphostin C suggests that Cd induction of
      HO-1 expression could be mediated by the PKC pathway in the BJAB cells together
      with the involvement of ERK 1/2 and JNK in a dose-dependent manner. The molecular
      and cellular pathways should not be considered separately. They should be viewed
      as an array of interconnecting signals, all contributing to the final outcome,
      thereby allowing fine control of the duration and extent of HO-1 induction.

PMID- 22659317
TI  - Developmental triclosan exposure decreases maternal, fetal, and early neonatal
      thyroxine: a dynamic and kinetic evaluation of a putative mode-of-action.
AB  - This work tests the mode-of-action (MOA) hypothesis that maternal and
      developmental triclosan (TCS) exposure decreases circulating thyroxine (T4)
      concentrations via up-regulation of hepatic catabolism and elimination of T4.
      Time-pregnant Long-Evans rats received TCS po (0-300mg/kg/day) from gestational
      day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from
      dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4,
      triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations were
      measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O
      depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme
      activities were measured in liver microsomes. Custom Taqman((r)) qPCR arrays were
      employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs,
      sulfotransferases, transporters, and thyroid hormone-responsive genes. TCS was
      quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30%
      in GD20 dams and fetuses, PND4 pups and PND22 dams (300mg/kg/day). Hepatic PROD
      activity increased 2-3 fold in PND4 pups and PND22 dams, and UGT activity was 1.5
      fold higher in PND22 dams only (300mg/kg/day). Minor up-regulation of Cyp2b and
      Cyp3a expression in dams was consistent with hypothesized activation of the
      constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams
      and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and
      PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic
      catabolism may contribute to TCS-induced hypothyroxinemia during development.
      Serum and liver TCS concentrations demonstrated greater fetal than postnatal
      internal exposure, consistent with the lack of T4 changes in PND14 and PND21
      offspring. These data support the MOA hypothesis that TCS exposure leads to
      hypothyroxinemia via increased hepatic catabolism; however, the minor effects on
      thyroid hormone metabolism may reflect the low efficacy of TCS as thyroid hormone
      disruptor or highlight the possibility that other MOAs may also contribute to the
      observed maternal and early neonatal hypothyroxinemia.

PMID- 22659319
TI  - Crystal structure of the coat protein of the flexible filamentous papaya mosaic
      virus.
AB  - Papaya mosaic virus (PapMV) is a filamentous plant virus that belongs to the
      Alphaflexiviridae family. Flexible filamentous viruses have defied more than two
      decades of effort in fiber diffraction, and no high-resolution structure is
      available for any member of the Alphaflexiviridae family. Here, we report our
      structural characterization of PapMV by X-ray crystallography and cryo-electron
      microscopy three-dimensional reconstruction. We found that PapMV is 135A in
      diameter with a helical symmetry of ~10 subunits per turn. Crystal structure of
      the C-terminal truncated PapMV coat protein (CP) reveals a novel all-helix fold
      with seven alpha-helices. Thus, the PapMVCP structure is different from the four
      helix-bundle fold of tobacco mosaic virus in which helix bundling dominates the
      subunit interface in tobacco mosaic virus and conveys rigidity to the rod virus.
      PapMV CP was crystallized as an asymmetrical dimer in which one protein lassoes
      the other by the N-terminal peptide. Mutation of residues critical to the inter
      subunit lasso interaction abolishes CP polymerization. The crystal structure
      suggests that PapMV may polymerize via the consecutive N-terminal loop lassoing
      mechanism. The structure of PapMV will be useful for rational design and
      engineering of the PapMV nanoparticles into innovative vaccines.

PMID- 22659320
TI  - Mechanism of dissociative inhibition of HIV protease and its autoprocessing from
      a precursor.
AB  - Dimerization is indispensible for release of the human immunodeficiency virus
      protease (PR) from its precursor (Gag-Pol) and ensuing mature-like catalytic
      activity that is crucial for virus maturation. We show that a single-chain Fv
      fragment (scFv) of a previously reported monoclonal antibody (mAb1696), which
      recognizes the N-terminus of PR, dissociates a dimeric mature D25N PR mutant with
      an enhanced dimer dissociation constant (K(d)) in the sub-micromolar range to
      form predominantly a monomer-scFv complex at a 1:1 ratio, along with small (5
      10%) amounts of a dimer-scFv complex. Enzyme kinetics indicate a mixed mechanism
      of inhibition of the wild-type PR, which exhibits a K(d)<10nM, with effects both
      on K(m) and k(cat) at an scFv-to-PR ratio of 10:1. ScFv binds to the N-terminal
      peptide P(1)QITLW(6) of PR and to PR monomers with dissociation constants of <=30
      nM and ~100 nM, respectively. Consistent with an ~400-fold increase in the
      dissociation of the antibody (K(Ab)) on even addition of an acetyl group to P(1)
      of the peptide, the antibody fails to inhibit N-terminal autoprocessing of the PR
      from a model precursor (at ~5 MUM). However, subsequent to this cleavage, it
      sequesters the PR, thus blocking autoprocessing at its C-terminus. A second
      monoclonal antibody [PRM1 (human monoclonal antibody to PR)], which recognizes
      part of the flap region (residues 41-47) of the mature PR and its precursor, does
      not inhibit autoprocessing and ensuing catalytic activity. However, its failure
      to recognize drug-resistant clinical mutants of PR may be beneficial to monitor
      the selection of mutations in this region under drug pressure.

PMID- 22659321
TI  - Structure-guided directed evolution of highly selective p450-based magnetic
      resonance imaging sensors for dopamine and serotonin.
AB  - New tools that allow dynamic visualization of molecular neural events are
      important for studying the basis of brain activity and disease. Sensors that
      permit ligand-sensitive magnetic resonance imaging (MRI) are useful reagents due
      to the noninvasive nature and good temporal and spatial resolution of MR methods.
      Paramagnetic metalloproteins can be effective MRI sensors due to the selectivity
      imparted by the protein active site and the ability to tune protein properties
      using techniques such as directed evolution. Here, we show that structure-guided
      directed evolution of the active site of the cytochrome P450-BM3 heme domain
      produces highly selective MRI probes with submicromolar affinities for small
      molecules. We report a new, high-affinity dopamine sensor as well as the first
      MRI reporter for serotonin, with which we demonstrate quantification of
      neurotransmitter release in vitro. We also present a detailed structural analysis
      of evolved cytochrome P450-BM3 heme domain lineages to systematically dissect the
      molecular basis of neurotransmitter binding affinity, selectivity, and enhanced
      MRI contrast activity in these engineered proteins.

PMID- 22659322
TI  - A role for loop F in modulating GABA binding affinity in the GABA(A) receptor.
AB  - The brain's major inhibitory neuroreceptor is the ligand-gated ion channel gamma
      aminobutyric acid (GABA) type A receptor (GABAR). GABARs exist in a variety of
      different subunit combinations that act to modulate the physiological behavior of
      GABAR by altering its pharmacological profile, as well as its affinity for GABA.
      While the alpha(1)beta(2)gamma(2) subtype is one of the most prevalent GABARs,
      the less populous alpha(6)beta(3)delta subtype has much higher GABA sensitivity.
      Previous studies identified residues crucial for GABA binding; however, the
      specific molecular differences responsible for this diverse sensitivity are not
      known. Furthermore, the role of loop F is a divisive subject, with conflicting
      evidence for ligand binding function. Using homology modeling, ligand docking,
      and molecular dynamics simulations, we investigated the GABA binding sites of the
      two receptor subtypes. Simulations identified seven residues that consistently
      interacted with GABA in both subtypes: alphaF65, alphaR132, betaL99, betaE155,
      betaR/K196, betaY205, and betaR207. Residue substitution at position beta196
      (arginine in alpha(6)beta(3)delta, lysine in alpha(1)beta(2)gamma(2)) resulted in
      a shift in GABA binding. However, the major difference between the two binding
      sites was the magnitude of loop F involvement, with a greater contribution in the
      alpha(6)beta(3)delta receptor. Free energy calculations confirm that the
      alpha(6)beta(3)delta binding pocket has an increased affinity for GABA. Thus, the
      possible role for loop F across the GABAR family is to modulate GABA affinity.

PMID- 22659324
TI  - Coexistence of two stage-structured intraguild predators.
AB  - An organism can be defined as omnivorous if it feeds on more than one trophic
      level. Omnivory is present in many ecosystems and multiple omnivorous species can
      coexist in the same ecosystem. How coexisting omnivores are able to avoid
      competitive exclusion is very much an open question. In this paper we analyze a
      model of a community consisting of two omnivorous predators and a basal resource.
      The population of both predators is explicitly structured into juveniles and
      adults, of which juveniles only feed on basal resource and adults feed on a
      varied proportion of basal resource and juveniles of the other population. We
      thereby separate the omnivorous roles (competitor for basal resource and predator
      of competitors) over life history. We show in this study that persistence of
      multiple omnivorous predators is possible when predators differ in adult diets.
      In this case, coexistence occurs because community dynamics force one of the
      model species to act as a predator and the other to act as a consumer. We
      conclude that separation of omnivorous roles over life history not only offers an
      explanation on why systems with omnivory can persist, but also how multiple
      omnivores can coexist at the same trophic levels of those systems.

PMID- 22659323
TI  - CheA-receptor interaction sites in bacterial chemotaxis.
AB  - In bacterial chemotaxis, transmembrane chemoreceptors, the CheA histidine kinase,
      and the CheW coupling protein assemble into signaling complexes that allow
      bacteria to modulate their swimming behavior in response to environmental
      stimuli. Among the protein-protein interactions in the ternary complex, CheA-CheW
      and CheW-receptor interactions were studied previously, whereas CheA-receptor
      interaction has been less investigated. Here, we characterize the CheA-receptor
      interaction in Thermotoga maritima by NMR spectroscopy and validate the
      identified receptor binding site of CheA in Escherichia coli chemotaxis. We find
      that CheA interacts with a chemoreceptor in a manner similar to that of CheW, and
      the receptor binding site of CheA's regulatory domain is homologous to that of
      CheW. Collectively, the receptor binding sites in the CheA-CheW complex suggest
      that conformational changes in CheA are required for assembly of the CheA-CheW
      receptor ternary complex and CheA activation.

PMID- 22659325
TI  - Tuning positive feedback for signal detection in noisy dynamic environments.
AB  - Learning from previous actions is a key feature of decision-making. Diverse
      biological systems, from neuronal assemblies to insect societies, use a
      combination of positive feedback and forgetting of stored memories to process and
      respond to input signals. Here we look how these systems deal with a dynamic two
      armed bandit problem of detecting a very weak signal in the presence of a high
      degree of noise. We show that by tuning the form of positive feedback and the
      decay rate to appropriate values, a single tracking variable can effectively
      detect dynamic inputs even in the presence of a large degree of noise. In
      particular, we show that when tuned appropriately a simple positive feedback
      algorithm is Fisher efficient, in that it can track changes in a signal on a time
      of order L(h)=(|h|/sigma)(-2), where |h| is the magnitude of the signal and sigma
      the magnitude of the noise.

PMID- 22659326
TI  - Fever, splenomegaly and lymphopenia in sarcoidosis. Visceral leishmaniasis.

PMID- 22659327
TI  - Towards understanding the functional diversity of cell wall mycolic acids of
      Mycobacterium tuberculosis.
AB  - Mycolic acids constitute the waxy layer of the outer cell wall of Mycobacterium
      spp. and a few other genera. They are diverse in structure, providing a unique
      chromatographic foot-print for almost each of the more than 70 Mycobacterium
      species. Although mainly esterified to cell wall arabinogalactan, trehalose or
      glucose, some free mycolic acid is secreted during in vitro growth of
      Mycobacterium tuberculosis. In M. tuberculosis, alpha-, keto- and methoxy-mycolic
      acids are the main classes, each differing in their ability to attract
      neutrophils, induce foamy macrophages or adopt an antigenic structure for
      antibody recognition. Of interest is their particular relationship to
      cholesterol, discovered by their ability to attract cholesterol, to bind
      Amphotericin B or to be recognised by monoclonal antibodies that cross-react with
      cholesterol. The structural elements that determine this diverse functionality
      include the carboxylic acid in the mycolic motif, as well as the nature and
      stereochemistry of the two functional groups in the merochain. The functional
      diversity of mycolic acid classes implies that much information may be contained
      in the selective expression and secretion of mycolic acids to establish
      tuberculosis after infection of the host. Their cholesteroid nature may relate to
      how they utilize host cholesterol for their persistent survival.

PMID- 22659328
TI  - The pharmacological treatment of pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a life-threatening and progressive
      disease of various origins characterized by pulmonary vascular remodeling that
      leads to increased pulmonary vascular resistance and pulmonary arterial pressure,
      most often resulting in right-sided heart failure. The most common symptom at
      presentation is breathlessness, with impaired exercise capacity as a hallmark of
      the disease. Advances in understanding the pathobiology over the last 2 decades
      have led to therapies (endothelin receptor antagonists, phosphodiesterase type 5
      inhibitors, and prostacyclins or analogs) initially directed at reversing the
      pulmonary vasoconstriction and more recently directed toward reversing
      endothelial cell dysfunction and smooth muscle cell proliferation. Despite these
      advances, disease progression is common even with use of combination regimens
      targeting multiple mechanistic pathways. Overall 5-year survival for PAH has
      increased significantly from approximately 30% in the 1980s to approximately 60%
      at present, yet remains abysmal. This review summarizes the mechanisms of action,
      clinical data, and regulatory histories of approved PAH therapies and describes
      the latest agents in late-stage clinical development.

PMID- 22659330
TI  - Methylmercury effects and exposures: who is at risk?

PMID- 22659331
TI  - Recent advances in nanocarrier-based mucosal delivery of biomolecules.
AB  - This review highlights the recent developments in the area of nanocarrier-based
      mucosal delivery of therapeutic biomolecules and antigens. Macromolecular drugs
      have the unique power to tackle challenging diseases but their structure,
      physicochemical properties, stability, pharmacodynamics, and pharmacokinetics
      place stringent demands on the way they are delivered into the body (e.g.,
      inability to cross mucosal surfaces and biological membranes). Carrier-based drug
      delivery systems can diminish the toxicity of therapeutic biomolecules, improve
      their bioavailability and make possible their administration via less-invasive
      routes (e.g., oral, nasal, pulmonary, etc.). Thus, the development of
      functionalized nanocarriers and nanoparticle-based microcarriers for the delivery
      of macromolecular drugs is considered an important scientific challenge and at
      the same time a business breakthrough for the biopharmaceutical industry. In
      order to be translated to the clinic the nanocarriers need to be biocompatible,
      biodegradable, stable in biological media, non-toxic and non-immunogenic, to
      exhibit mucoadhesive properties, to cross mucosal barriers and to protect their
      sensitive payload and deliver it to its target site in a controlled manner, thus
      increasing significantly its bioavailability and efficacy.

PMID- 22659329
TI  - Cisplatin resistance: a cellular self-defense mechanism resulting from multiple
      epigenetic and genetic changes.
AB  - Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its
      effectiveness seems to be due to the unique properties of cisplatin, which enters
      cells via multiple pathways and forms multiple different DNA-platinum adducts
      while initiating a cellular self-defense system by activating or silencing a
      variety of different genes, resulting in dramatic epigenetic and/or genetic
      alternations. As a result, the development of cisplatin resistance in human
      cancer cells in vivo and in vitro by necessity stems from bewilderingly complex
      genetic and epigenetic changes in gene expression and alterations in protein
      localization. Extensive published evidence has demonstrated that pleiotropic
      alterations are frequently detected during development of resistance to this
      toxic metal compound. Changes occur in almost every mechanism supporting cell
      survival, including cell growth-promoting pathways, apoptosis, developmental
      pathways, DNA damage repair, and endocytosis. In general, dozens of genes are
      affected in cisplatin-resistant cells, including pathways involved in copper
      metabolism as well as transcription pathways that alter the cytoskeleton, change
      cell surface presentation of proteins, and regulate epithelial-to-mesenchymal
      transition. Decreased accumulation is one of the most common features resulting
      in cisplatin resistance. This seems to be a consequence of numerous epigenetic
      and genetic changes leading to the loss of cell-surface binding sites and/or
      transporters for cisplatin, and decreased fluid phase endocytosis.

PMID- 22659332
TI  - Prostatic needle biopsies following primary high intensity focused ultrasound
      (HIFU) therapy for prostatic adenocarcinoma: histopathological features in tumour
      and non-tumour tissue.
AB  - AIMS: High intensity focused ultrasound (HIFU) is currently offered as primary
      treatment for patients with clinically localised prostate cancer. Data on
      histopathological features of post-treatment biopsies are limited. METHODS:
      Pretreatment biopsies were identified in 45 men (age range 41-85) who received
      primary HIFU therapy. Post-HIFU biopsies were performed in 30 of these patients
      (67%) at mean 14.1 months (95% CI 11.7 to 16.5) follow-up, 22 due to rising PSA
      and eight as part of routine follow-up. Biopsies were examined for presence,
      distribution and extent of adenocarcinoma, Gleason scores, use of standard
      immunohistochemistry and ablative tissue changes were attributable to HIFU.
      RESULTS: In post-HIFU biopsies performed for biochemical failure, 17/22 (77%)
      contained adenocarcinoma; 4/22 (18%) had higher post-HIFU Gleason score; 3/22
      (14%) had newly recognised bilateral involvement; and 4/22 (18%) had higher
      percentage tissue involvement compared with pre-HIFU biopsies. Of cases without
      rising post-HIFU PSA, 2/8 (25%) routine follow-up biopsies contained
      adenocarcinoma. Stromal fibrosis was the commonest finding in non-tumour post
      HIFU biopsy tissue (17/30, 57%) with coagulative necrosis occurring in fewer
      cases (4/30, 13%) and over a shorter follow-up interval than cases showing
      fibrosis (8.5 (0.2-16.8) vs 15.3 (11.5-19.1) months). Treatment effects in tumour
      cells precluding the assignment of Gleason scores or use of immunohistochemistry
      in post-HIFU biopsies were not identified. CONCLUSION: Post-HIFU biopsies are
      positive in more than 75% of patients with elevated or rising PSA. Stromal
      fibrosis is common but the tissue effects of this modality do not appear to
      impair pathologists' ability to detect and grade adenocarcinoma in follow-up
      biopsies.

PMID- 22659333
TI  - Fibrosing variant of Hashimoto thyroiditis is an IgG4 related disease.
AB  - Hashimoto thyroiditis (HT) and the fibrosing variant of Hashimoto thyroiditis
      (FVHT) are immune-mediated tumefactive lesions of the thyroid. Immunoglobulin G4
      related disease (IgG4-RD) is now a widely recognised multi-organ system disease
      characterised by elevated serum and tissue concentrations of IgG4. In this study,
      the authors address several unresolved questions pertaining to the relationship
      between HT and FVHT, and the association of each of these diseases with IgG4-RD.
      The authors evaluated 28 consecutive cases of HT and nine cases of FVHT. The
      clinical, demographic and serological data were recorded. The slides were stained
      immunohistochemically using antibodies to IgG4 and IgG and the quantitative
      analysis was recorded. Data on thyroid function tests were available on seven
      cases of FVHT and 14 cases of HT. Based on the availability of data,
      hypothyroidism was noted in 62% (9/14) of HT and 86% of FVHT (6/7). FVHT
      demonstrated an exaggerated lobular pattern with lobules separated by cellular
      storiform-type fibrosis, resembling fibrosis seen in other forms of IgG-RD. The
      median IgG4 counts per high power field (*40) in HT and FVHT were 2.3 and 22,
      respectively. The median IgG4:IgG ratios in HT and FVHT were 0.11 and 0.58,
      respectively. The authors propose that FVHT belongs to the spectrum of IgG4-RD.
      Although a proportion of cases of HT show elevated numbers of IgG4 positive
      plasma cells, these cases lack the histological features typically associated
      with IgG4-RD, and thus the relationship between HT and IgG4-RD remains unproven.

PMID- 22659334
TI  - Association of plasma cell subsets in the bone marrow and free light chain
      concentrations in the serum of monoclonal gammopathy patients.
AB  - This study investigated bone marrow plasma cell subsets and monoclonal free light
      chain concentrations in blood of monoclonal gammopathy patients. 54 bone marrow
      samples were stained by double immunofluorescence to enumerate cellular subsets
      making either intact monoclonal immunoglobulin or free light chains only. Blood
      taken at the same time was assayed for free light chains by an automated
      immunoassay. Patients were assigned to three cellular population categories:
      single intact monoclonal immunoglobulin (59%), dual monoclonal immunoglobulin and
      free light chain only (31%), or single free light chain only (9%). The median
      affected free light chain concentration of each group was 75 mg/l, 903 mg/l and
      3320 mg/l, respectively, but with substantial overlap. In myeloma patients the
      difference in serum free light chain concentrations between patients with free
      light chain only marrow cells and those without was statistically significant.
      Serum free light chain levels >600 mg/l result mostly from marrow cells
      restricted to free light chain production.

PMID- 22659335
TI  - Integrin alpha7beta1 is a redox-regulated target of hydrogen peroxide in vascular
      smooth muscle cell adhesion.
AB  - Upon adhesion to laminin-111, aortic smooth muscle cells initially form membrane
      protrusions with an average diameter of 2.9MUm. We identified these protrusions
      also as subcellular areas of increased redox potential and protein oxidation by
      detecting cysteine sulfenic acid groups with dimedone. Hence, we termed these
      areas oxidative hot spots. They are spatially and temporally transient during an
      early stage of adhesion and depend on the activity of the H(2)O(2)-generating
      NADPH oxidase 4. Presumably located on cellular protrusions, integrin alpha7beta1
      mediates adhesion and migration of vascular smooth muscle cells to laminins of
      their surrounding basement membrane. Using protein chemistry and mass
      spectrometry, two specific oxidation sites within the integrin alpha7 subunit
      were identified: one located in its genu region and another within its calf 2
      domain. Upon H(2)O(2) treatment, two cysteine residues are oxidized thereby
      unlocking a disulfide bridge. The genu region is a hinge, around which the
      integrin domains pivot between a bent/inactive and an upright/active
      conformation. Also, cysteine oxidation within the calf 2 domain permits
      conformational changes related to integrin activation. H(2)O(2) treatment of
      alpha7beta1 integrin in concentrations of up to 100MUM increases integrin binding
      activity to laminin-111, suggesting a physiological redox regulation of
      alpha7beta1 integrin.

PMID- 22659336
TI  - Two sRNA RyhB homologs from Yersinia pestis biovar microtus expressed in vivo
      have differential Hfq-dependent stability.
AB  - Small non-coding RNAs (sRNAs) have been shown to modulate gene expression at the
      post-transcriptional level. RyhB, an iron-responsive sRNA, is conserved in
      Escherichia coli and other Enterobacteriae, indicating the downregulation of
      numerous genes during iron depletion. This sRNA is tightly regulated by the
      ferric uptake regulator (Fur) and interacts with the RNA binding protein Hfq. Hfq
      is generally purported to be essential for stabilizing sRNAs and promoting sRNA
      mRNA duplex formation. Maintenance of iron homeostasis is an essential step in
      the lifecycle of Yersinia pestis. Y. pestis encodes two RyhB homologs, RyhB1 and
      RyhB2. In this study, we found that as in the case of E. coli, both RyhB homologs
      in Y. pestis are negatively regulated by Fur and have a half-life of >30 min. In
      the absence of Hfq, RyhB1 is rapidly degraded, while RyhB2 retains its stability.
      RyhB1 stabilization is mediated by Hfq, but RyhB2 does not require Hfq for
      stability. Additionally, both RyhBs are upregulated in lungs infected with Y.
      pestis, while the ryhB mutant shows no visible effects on virulence in mice upon
      either subcutaneous or intranasal inoculation. Collectively, our results indicate
      that the two RyhB homologs have common regulatory features in Y. pestis-infected
      lungs and in vitro, but that stability of RyhB1 and RyhB2 is differentially
      dependent on Hfq.

PMID- 22659337
TI  - Involvement of the ammonium transporter AmtB in nitrogenase regulation and
      ammonium excretion in Pseudomonas stutzeri A1501.
AB  - The nitrogen-fixing Pseudomonas stutzeri strain A1501 contains two ammonium
      transporter genes, amtB1 and amtB2, linked to glnK. Growth of an amtB1-amtB2
      double deletion mutant strain was not impaired compared to that of the wild type
      under any conditions tested, and it was still capable of taking up ammonium ions
      at nearly wild-type rates. Nitrogenase activity was repressed in wild-type strain
      A1501 in response to the addition of ammonium, but nitrogenase activity was only
      partially impaired in the amtB1 and amtB2 double mutant, suggesting that the two
      AmtB proteins are involved in regulating expression of nitrogenase or its
      activity in response to ammonium. An interaction between GlnK and AmtB1 or AmtB2
      was observed in a yeast two-hybrid assay. Ammonium was excreted by the amtB
      double mutant strain under nitrogen fixation conditions, particularly when nifA
      was expressed constitutively. This suggests that AmtB proteins play a role in
      controlling the internal pool of ammonia within the cell.

PMID- 22659338
TI  - A ZnO-doped adhesive reduced collagen degradation favouring dentine
      remineralization.
AB  - OBJECTIVES: The objective of the study was to determine the efficacy of a ZnO
      doped etch and rinse adhesive in decreasing MMPs-mediated collagen degradation at
      the resin-dentine hybrid layer, and increasing bonding stability. METHODS: C
      terminal telopeptide concentrations (ICTP) were determined after 24h, 1wk and 4wk
      in human dentine beams. Dentine was treated: (1) 37% phosphoric acid for 15s
      (PA), (2) PA-etched dentine infiltrated with Single Bond (SB), (3) PA-etched
      dentine infiltrated with ZnO doped SB (ZnO particles--10wt%--were added to the
      bonding resin) (ZnO-SB), and (4) Clearfil SE Bond primed-dentine was infiltrated
      with Clearfil SE bonding resin (CSE). Microtensile bond strength (MTBS) was
      assessed for the different groups at 24h and after 3months. Debonded dentine
      surfaces were studied by scanning electron microscopy. RESULTS: MMPs-mediated
      collagen degradation occurred in demineralized dentine (PA). Resin infiltration
      decreased collagen degradation. The lowest collagen degradation was found for Zn
      doped SB, followed by CSE. When these adhesives were applied, ICTP values did not
      change throughout the study period. At 24h, similar MTBS was attained for all
      adhesives. Only SB decreased MTBS after three months. CONCLUSIONS: Addition of
      ZnO particles to SB produced a reduction in dentine collagen degradation and
      increased resin-dentine bonds durability. In Zn-doped adhesive interfaces, a
      calcium phosphate layer and tubular occlusion was encountered at the debonded
      interface. CLINICAL SIGNIFICANCE: ZnO particles addition into the bonding resin
      of SB makes a breakthrough to prevent the hybrid layer degradation and to
      preserve its bonding efficacy overtime.

PMID- 22659339
TI  - Randomized clinical trial on single retainer all-ceramic resin-bonded fixed
      partial dentures: Influence of the bonding system after up to 55 months.
AB  - OBJECTIVES: This study evaluated the clinical outcome of all-ceramic resin-bonded
      fixed partial dentures (RBFPDs) with a cantilevered single-retainer design.
      METHODS: Thirty anterior zirconia ceramic RBFPDs were inserted using either a
      phosphate monomer containing resin (Panavia 21 TC; N=16) or an adhesive bonding
      system with a phosphoric acid acrylate primer (Multilink-Automix with
      Metal/Zirconia primer; N=14). RESULTS: During a mean observation time of 41.7
      months one debonding occurred in each group. Both RBFPDs could be rebonded
      successfully resulting in a three-year survival rate of 100%. CONCLUSION:
      Independent of the bonding system cantilevered zirconia ceramic RBFPDs showed
      promising results during the first three years. CLINICAL SIGNIFICANCE: Single
      retainer zirconia ceramic RBFPD present an alternative treatment option offering
      good aesthetics, a minimal invasive preparation, a high biocompatibility and can
      even be used to treat juvenile patients who do not yet come into consideration
      for implant placement. No significant influence of the bonding system used was
      detected so far.

PMID- 22659340
TI  - Easy preparation of a large-size random gene mutagenesis library in Escherichia
      coli.
AB  - A simple and fast protocol for the preparation of a large-size mutant library for
      directed evolution in Escherichia coli was developed based on the DNA multimers
      generated by prolonged overlap extension polymerase chain reaction (POE-PCR).
      This protocol comprised the following: (i) a linear DNA mutant library was
      generated by error-prone PCR or shuffling, and a linear vector backbone was
      prepared by regular PCR; (ii) the DNA multimers were generated based on these two
      DNA templates by POE-PCR; and (iii) the one restriction enzyme-digested DNA
      multimers were ligated to circular plasmids, followed by transformation to E.
      coli. Because the ligation efficiency of one DNA fragment was several orders of
      magnitude higher than that of two DNA fragments for typical mutant library
      construction, it was very easy to generate a mutant library with a size of more
      than 10(7) protein mutants per 50 MUl of the POE-PCR product. Via this method,
      four new fluorescent protein mutants were obtained based on monomeric cherry
      fluorescent protein. This new protocol was simple and fast because it did not
      require labor-intensive optimizations in restriction enzyme digestion and
      ligation, did not involve special plasmid design, and enabled constructing a
      large-size mutant library for directed enzyme evolution within 1 day.

PMID- 22659341
TI  - A novel in vitro human microglia model: characterization of human monocyte
      derived microglia.
AB  - Microglia are the innate immune cells of the central nervous system. They help
      maintaining physiological homeostasis and contribute significantly to
      inflammatory responses in the course of infection, injury and degenerative
      processes. To date, there is no standardized simple model available to
      investigate the biology of human microglia. The aim of this study was to
      establish a new human microglia model. For that purpose, human peripheral blood
      monocytes were cultured in serum free medium in the presence of M-CSF, GM-CSF,
      NGF and CCL2 to generate monocyte-derived microglia (M-MG). M-MG were clearly
      different in morphology, phenotype and function from freshly isolated monocytes,
      cultured monocytes in the absence of the cytokines and monocyte-derived dendritic
      cells (M-DC) cultured in the presence of GM-CSF and IL-4. M-MG acquired a
      ramified morphology with primary and secondary processes. M-MG displayed a
      comparable phenotype to the human microglia cell line HMC3, expressing very low
      levels of CD45, CD14 and HLA-DR, CD11b and CD11c; and undetectable levels of
      CD40, CD80 and CD83, and a distinct pattern of chemokine receptors (positive for
      CCR1, CCR2, CCR4, CCR5, CXCR1, CXCR3, CX3CR1; negative for CCR6 and CCR7). In
      comparison with M-DC, M-MG displayed lower T-lymphocyte stimulatory capacity, as
      well as lower phagocytosis activity. The described protocol for the generation of
      human monocyte-derived microglia is feasible, well standardized and reliable, as
      it uses well defined culture medium and recombinant cytokines, but no serum or
      conditioned medium. This protocol will certainly be very helpful for future
      studies investigating the biology and pathology of human microglia.

PMID- 22659342
TI  - Blebbing as a physical force in cancer EMT - parallels with mitosis.
AB  - Epithelial to mesenchymal transition (EMT) during metastasis is initially a two
      step process beginning with delamination of cells from the solid tumor followed
      by acquisition of a migratory phenotype. Several reports indicate that plasma
      membrane blebbing, associated with cell division, coincides with cell
      delamination during developmental EMT. This raises a speculative question if
      blebbing drives EMT in cancer cells in a similar way. Here, we review available
      data on factors and processes that may support such a connection.

PMID- 22659343
TI  - Sporadic male patients with intellectual disability: contribution of X-chromosome
      copy number variants.
AB  - Genome-wide array comparative genome hybridization has become the first in line
      diagnostic tool in the clinical work-up of patients presenting with intellectual
      disability. As a result, chromosome X-copy number variations are frequently being
      detected in routine diagnostics. We retrospectively reviewed genome wide array
      CGH data in order to determine the frequency and nature of chromosome X-copy
      number variations (X-CNV) in a cohort of 2222 sporadic male patients with
      intellectual disability (ID) referred to us for diagnosis. In this cohort, 68
      males were found to have at least one X-CNV (3.1%). However, correct
      interpretation of causality remains a challenging task, and is essential for
      proper counseling, especially when the CNV is inherited. On the basis of these
      data, earlier experience and literature data we designed and propose an algorithm
      that can be used to evaluate the clinical relevance of X-CNVs detected in
      sporadic male ID patients. Applied to our cohort, 19 male ID patients (0.85%)
      were found to carry a (likely) pathogenic X-CNV.

PMID- 22659344
TI  - Generation of metabolically functioning hepatocytes from human pluripotent stem
      cells by FOXA2 and HNF1alpha transduction.
AB  - BACKGROUND & AIMS: Hepatocyte-like cells differentiated from human embryonic stem
      cells (hESCs) and induced pluripotent stem cells (hiPSCs) can be utilized as a
      tool for screening for hepatotoxicity in the early phase of pharmaceutical
      development. We have recently reported that hepatic differentiation is promoted
      by sequential transduction of SOX17, HEX, and HNF4alpha into hESC- or hiPSC
      derived cells, but further maturation of hepatocyte-like cells is required for
      widespread use of drug screening. METHODS: To screen for hepatic differentiation
      promoting factors, we tested the seven candidate genes related to liver
      development. RESULTS: The combination of two transcription factors, FOXA2 and
      HNF1alpha, promoted efficient hepatic differentiation from hESCs and hiPSCs. The
      expression profile of hepatocyte-related genes (such as genes encoding cytochrome
      P450 enzymes, conjugating enzymes, hepatic transporters, and hepatic nuclear
      receptors) achieved with FOXA2 and HNF1alpha transduction was comparable to that
      obtained in primary human hepatocytes. The hepatocyte-like cells generated by
      FOXA2 and HNF1alpha transduction exerted various hepatocyte functions including
      albumin and urea secretion, and the uptake of indocyanine green and low density
      lipoprotein. Moreover, these cells had the capacity to metabolize all nine tested
      drugs and were successfully employed to evaluate drug-induced cytotoxicity.
      CONCLUSIONS: Our method employing the transduction of FOXA2 and HNF1alpha
      represents a useful tool for the efficient generation of metabolically functional
      hepatocytes from hESCs and hiPSCs, and the screening of drug-induced
      cytotoxicity.

PMID- 22659345
TI  - Polymorphisms of DNA repair genes in Korean hepatocellular carcinoma patients
      with chronic hepatitis B: possible implications on survival.
AB  - BACKGROUND & AIMS: We aimed at determining whether single nucleotide
      polymorphisms (SNPs) of DNA repair genes influence the development and clinical
      outcomes of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).
      METHODS: We evaluated 14 SNPs of eight DNA repair genes in 708 patients with HCC
      and 388 HBsAg positive controls without HCC. The Kaplan-Meier methods with log
      rank test and Cox regression models were used to compare survival of HCC patients
      according to the genotype. RESULTS: The SNP of XRCC4 rs1805377 was significantly
      associated with decreased risk of HCC development (OR, 0.592; p=0.028) and
      improved overall survival of patients with HCC (median survival time (MST) of 48,
      72, and 89 months for the AA, AG, and GG genotypes, respectively; p=0.044). In
      addition, SNP of OGG1 rs1053133 was significantly associated with postoperative
      recurrence (OR, 0.604; p=0.049), tumor differentiation (OR, 0.571; p=0.041), and
      improved survival of resected HCC (MST of 55 and 108 months for the GG and GC/CC
      genotypes, p=0.001). The multivariate analysis showed that OGG1 rs1052133, XRCC1
      rs25487, ERCC5 rs2018836, ERCC5 rs3818356, and XRCC4 rs1805377 had a significant
      effect on survival. Moreover, a strong dose-dependent association was observed
      between the number of putative high-risk genotypes of OGG1, XRCC1, ERCC5, and
      XRCC4 with the overall survival. The MST of HCC with >=2 putative high-risk
      genotypes was significantly prolonged compared to those with >=3 high-risk
      genotypes (76 vs. 46 months, respectively, p=0.002). CONCLUSIONS: Polymorphisms
      of DNA repair genes play a potential role in the development, progression, and
      survival of Korean HCC patients with chronic HBV infection.

PMID- 22659347
TI  - Existence of complex patterns in the Beddington-DeAngelis predator-prey model.
AB  - The study of reaction-diffusion system constitutes some of the most fascinating
      developments of late twentieth century mathematics and biology. This article
      investigates complexity and chaos in the complex patterns dynamics of the
      original Beddington-DeAngelis predator-prey model which concerns the influence of
      intra species competition among predators. We investigate the emergence of
      complex patterns through reaction-diffusion equations in this system. We derive
      the conditions for the codimension-2 Turing-Hopf, Turing-Saddle-node, and Turing
      Transcritical bifurcation, and the codimension-3 Turing-Takens-Bogdanov
      bifurcation. These bifurcations give rise to very complex patterns that have not
      been observed in previous predator-prey models. A large variety of different
      types of long-term behavior, including homogenous distributions and stationary
      spatial patterns are observed through extensive numerical simulations with
      experimentally-based parameter values. Finally, a discussion of the ecological
      implications of the analytical and numerical results concludes the paper.

PMID- 22659346
TI  - The role of CX3CL1/CX3CR1 in pulmonary angiogenesis and intravascular monocyte
      accumulation in rat experimental hepatopulmonary syndrome.
AB  - BACKGROUND & AIMS: Hepatopulmonary syndrome (HPS), classically attributed to
      intrapulmonary vascular dilatation, occurs in 15-30% of cirrhotics and causes
      hypoxemia and increases mortality. In experimental HPS after common bile duct
      ligation (CBDL), monocytes adhere in the lung vasculature and produce vascular
      endothelial growth factor (VEGF)-A and angiogenesis ensues and contribute to
      abnormal gas exchange. However, the mechanisms for these events are unknown. The
      chemokine fractalkine (CX(3)CL1) can directly mediate monocyte adhesion and
      activate VEGF-A and angiogenesis via its receptor CX(3)CR1 on monocytes and
      endothelium during inflammatory angiogenesis. We explored whether pulmonary
      CX(3)CL1/CX(3)CR1 alterations occur after CBDL and influence pulmonary
      angiogenesis and HPS. METHODS: Pulmonary CX(3)CL1/CX(3)CR1 expression and
      localization, CX(3)CL1 signaling pathway activation, monocyte accumulation, and
      development of angiogenesis and HPS were assessed in 2- and 4-week CBDL animals.
      The effects of a neutralizing antibody to CX(3)CR1 (anti-CX(3)CR1 Ab) on HPS
      after CBDL were evaluated. RESULTS: Circulating CX(3)CL1 levels and lung
      expression of CX(3)CL1 and CX(3)CR1 in intravascular monocytes and microvascular
      endothelium increased in 2- and 4-week CBDL animals as HPS developed. These
      events were accompanied by pulmonary angiogenesis, monocyte accumulation,
      activation of CX(3)CL1 mediated signaling pathways (Akt, ERK) and increased VEGF
      A expression and signaling. Anti-CX(3)CR1 Ab treatment reduced monocyte
      accumulation, decreased lung angiogenesis and improved HPS. These events were
      accompanied by inhibition of CX(3)CL1 signaling pathways and a reduction in VEGF
      A expression and signaling. CONCLUSIONS: Circulating CX(3)CL1 levels and
      pulmonary CX(3)CL1/CX(3)CR1 expression and signaling increase after CBDL and
      contribute to pulmonary intravascular monocyte accumulation, angiogenesis and
      development of experimental HPS.

PMID- 22659348
TI  - Experiences of young women living with developmental dysplasia of the hip:
      insight into their experiences of surgery and recovery.
AB  - OBJECTIVE: To explore the experiences of young women with developmental dysplasia
      of the hip explicating the impact of peri-acetabular osteotomy surgery and
      recovery in the short and longer term. DESIGN: Postings of five, selected women
      on an online active message board aimed at women with developmental dysplasia of
      the hip were analysed. Interest lay on their postings after they had had peri
      acetabular osteotomy surgery. Data analysis was performed through the approach of
      interpretive phenomenological analysis. RESULTS: The time length of the postings
      for the cases ranged from 1 year to 6 years, and the number of postings varied
      substantially, from 48 to 591. Two major concepts were prominent across
      participants' accounts. The first concept, 'body image', centred on affects on
      the women's self-esteem and body image. The second, 'the long road to recovery',
      highlighted 'the emotional and physical battle of learning to walk' and concerns
      with 'saving my joints'. CONCLUSION: Developmental dysplasia of the hip
      potentially provides a critical case for exploration of the process of how a
      disability can affect confidence, self-esteem and body image. Recovery from this
      condition requires enormous effort, resilience and commitment from the women.

PMID- 22659349
TI  - Meeting the mental health needs of people with chronic obstructive pulmonary
      disease: a qualitative study.
AB  - OBJECTIVES: This study aimed to understand the mental health needs of people
      living with chronic obstructive pulmonary disease: what they were experiencing,
      what they wanted (or did not want) which might be described as 'felt need', what
      they had accessed or received ('expressed need') and how, from their perspective,
      their emotional needs might be more effectively met by health care services.
      METHODS: Qualitative study with 14 patients with a confirmed diagnosis of chronic
      obstructive pulmonary disease, where a member of the clinical team had recognised
      that the patient was suffering from associated emotional distress. RESULTS: Three
      themes emerged: a sense of assuming a different identity as the disease
      challenged abilities, the experience of social isolation with fear of dependence
      and barriers the participants encountered acting as obstacles to coping, adapting
      and accessing treatments. There were mixed feelings about the value of talking
      about problems, with both psychological and physical barriers strongly militating
      against both expression of need and utilization of care offered. CONCLUSIONS:
      Innovative research and clinical care should be aimed towards development of
      skills, strategies and systems required to engage sensitively and negotiate needs
      for care, in a patient-centred manner, with people who do not necessarily see the
      need to ask for emotional support.

PMID- 22659350
TI  - Coping with chronic complex regional pain syndrome: advice from patients for
      patients.
AB  - OBJECTIVE: To explore what advice people currently living with chronic complex
      regional pain syndrome would offer to another person coming to terms with a
      diagnosis of chronic complex regional pain syndrome. METHODS: Semi-structured
      interviews with 21 adults (5 male) living with chronic complex regional pain
      syndrome who had completed a complex regional pain syndrome rehabilitation
      programme were conducted. RESULTS: Effectively self-managing complex regional
      pain syndrome required individuals to play an active role. This could only be
      achieved if they felt they had sufficient control. Means of attaining control
      involved attaining a level of acceptance, becoming well-informed and accessing
      the right kind of support. The advice offered by patients for patients largely
      reflected that offered by healthcare professionals. One area where there was a
      conflict concerned sleep hygiene. CONCLUSIONS: Our study provides support both
      for the argument put forward by Redman that without appropriate preparation and
      support, self-management is ineffective, and that by Skuladottir and Hallsdottir
      that the main challenge of the chronic pain trajectory is that of retaining a
      sense of control. The clinical implications of this are discussed.

PMID- 22659351
TI  - Enhanced multiplex PCR assay for typing of staphylococcal cassette chromosome mec
      types I to V in methicillin-resistant Staphylococcus aureus.
AB  - We previously published a simple multiplex PCR assay for quick-screening of
      Staphylococcal Cassette Chromosome mec (SCCmec) types I-V, which has been
      extensively used worldwide. An updated assay is described here and the changes
      serve to make this rapid assay more accurate and reliable in facilitating
      identification of most common and major SCCmec types.

PMID- 22659352
TI  - Modelling the effects of cell-cycle heterogeneity on the response of a solid
      tumour to chemotherapy: biological insights from a hybrid multiscale cellular
      automaton model.
AB  - The therapeutic control of a solid tumour depends critically on the responses of
      the individual cells that constitute the entire tumour mass. A particular cell's
      spatial location within the tumour and intracellular interactions, including the
      evolution of the cell-cycle within each cell, has an impact on their decision to
      grow and divide. They are also influenced by external signals from other cells as
      well as oxygen and nutrient concentrations. Hence, it is important to take these
      into account when modelling tumour growth and the response to various treatment
      regimes ('cell-kill therapies'), including chemotherapy. In order to address this
      multiscale nature of solid tumour growth and its response to treatment, we
      propose a hybrid, individual-based approach that analyses spatio-temporal
      dynamics at the level of cells, linking individual cell behaviour with the
      macroscopic behaviour of cell organisation and the microenvironment. The
      individual tumour cells are modelled by using a cellular automaton (CA) approach,
      where each cell has its own internal cell-cycle, modelled using a system of ODEs.
      The internal cell-cycle dynamics determine the growth strategy in the CA model,
      making it more predictive and biologically relevant. It also helps to classify
      the cells according to their cell-cycle states and to analyse the effect of
      various cell-cycle dependent cytotoxic drugs. Moreover, we have incorporated the
      evolution of oxygen dynamics within this hybrid model in order to study the
      effects of the microenvironment in cell-cycle regulation and tumour treatments.
      An important factor from the treatment point of view is that the low
      concentration of oxygen can result in a hypoxia-induced quiescence (G0/G1 arrest)
      of the cancer cells, making them resistant to key cytotoxic drugs. Using this
      multiscale model, we investigate the impact of oxygen heterogeneity on the spatio
      temporal patterning of the cell distribution and their cell-cycle status. We
      demonstrate that oxygen transport limitations result in significant heterogeneity
      in HIF-1 alpha signalling and cell-cycle status, and when these are combined with
      drug transport limitations, the efficacy of the therapy is significantly
      impaired.

PMID- 22659353
TI  - Head and neck lymphomas--diagnostic difficulties.
AB  - Malignant lymphomas represent approximately 5% of all malignant neoplasm of the
      head and neck and may involve nodal or extranodal sites. The head and neck region
      is the second most frequent anatomical site of extranodal lymphomas (after the
      gastrointestinal tract). Most are non-Hodgkin lymphomas (NHL) of B-cell lineage.
      Hodgkin's lymphoma (HL) rarely occurs in extranodal site. THE AIM OF THE STUDY
      was to evaluate head and neck manifestation of lymphoma (both HL and NHL) and
      emphasize diagnostic difficulties of these pathologies. MATERIAL AND METHODS:
      Retrospective review of medical records of patients diagnosed for lymphomas in
      our department was performed. Authors analyzed demographic data as well as
      clinical manifestation and diagnostic trials. RESULTS: 9 patients were included
      to the study. 7 of them suffered from extranodal NHL and 2 of them from HL (one
      patient--extranodal and one nodal manifestation). There were diagnostic
      complications in all cases and final diagnosis was made after surgical material
      analysis. CONCLUSIONS: This data demonstrate low sensivity of fine needle
      aspiration for identification of lymphoma as well as clinical picture is non
      characteristic.

PMID- 22659354
TI  - Colour Doppler assessment of the perforators of anterolateral thigh flap and its
      usefulness in preoperative planning.
AB  - The role of the anterolateral thigh flap (ALTF) in reconstructive microsurgery
      grows systematically from mid-eighties of the twenty century until now.
      Significant anatomic variability of the perforators supplying the ALTF was
      described in literature. THE AIM OF THE STUDY was ultrasonographic assessment of
      the ALTF perforators in terms of localization, symmetry, diameter and flow
      velocity. MATERIAL AND METHODS: The study was performed using ultrasound machine
      with 12 MHz linear transducer. Both thighs of 30 healthy volunteers (15 men and
      15 women) aged from 18 to 60 (mean 37.9) were examined. The line from anterior
      superior iliac spine (ASIS) to lateral border of the patella was traced, and
      divided into 10 equal segments. Point where perforator pierces the deep fascia
      was marked and its diameter was measured and recorded. Maximal flow velocity was
      measured and recorded. Symmetry of perforator location was confirmed as positive
      if difference in position of two perforators on both thighs was less than 1.5 cm
      in diameter. RESULTS: Total number of 119 perforators supplying skin of 60 thighs
      was found (mean 1.98 perforator per thigh). No perforators were found in 4 thighs
      (6.6%). Perforators were most abundant in segments from 5 to 7 (74.6%).
      Perforators with largest diameters and maximal flow velocity reaching 30-47 cm/s
      were localized in segments 5 and 6. Perforators in segments 4 and 5 were more
      abundant in men (50.9%) than in women (36.7%). Septal perforators make up to
      26.9% of the total. Eighty percent of the septal perforators were localized in
      segments 5 and 6. Perforator distribution was elicited in the middle of the ASIS-
      patella line. In the range of +/-1.5 cm from the midpoint of the line 33.6% of
      the perforators were found. CONCLUSIONS: 1. Most of perforators with large
      diameter and big flow velocity are located in segments 5 and 6. 2. Perforators
      are more common in men in segments 4 and 5 than in women. 3. No perforators found
      in 4 thighs suggests that preoperative perforator mapping should become a
      preoperative routine, which can spare intraoperative dilemmas.

PMID- 22659355
TI  - Rusults of classical crawford and hybrid operations in thoracic-abdominal aorta
      aneurysms treatment--comparative assessment.
AB  - Thoracic-abdominal aortic aneurysms (TAAA) are still serious medical problem.
      Classical procedure requires two cavities approach and implantation of vascular
      prosthetic in the place of aneurysm--Crawford's procedure. Significant progress
      was made during last years by using endovascular procedures (stentgrafts).
      Alternative is hybrid procedure--prosthetic appliance of visceral and kidney
      arteries and then stentgraft implantation in whole thoracic-abdominal aorta. THE
      AIM OF THE STUDY was comparative analysis of classical and hybrid procedures in
      thoracic-abdominal aneurysms treatment. MATERIAL AND METHODS: Between 1989-2011
      in Department of Vascular, General and Transplantological Surgery Medical
      University in Wroclaw and Surgical Department of 4th Military Clinical Hospital
      in Wroclaw 53 patients were operated due to thoracic-abdominal aortic aneurysms.
      Classical Crawford's procedure was performed in 41 patients (group I) and hybrid
      procedure was performed in 12 patients (group II). Additionally 7 patients
      required aortic arc branches reconstruction due to achieve optimal conditions to
      stentgraft amplantation. Procedures were performed at one or two stages. RESULTS:
      Mortality in patients treated classically (group I) depended on type of aneurysm
      in Crawford's classification. In type I-II mortality rate was 54% ((7 deaths/12
      patients), in type III do V 17% (5 deaths/ 29 patients). In the group after
      hybrid procedure (group II) mortality rate was 28% (2 deaths/ 7 patients) in type
      I-II and 20% (1 death/5 patients) in type III to V. Observed serious
      perioperative complications. CONCLUSIONS: 1. Endovascular procedures development
      enabled introducing of new methods in thoracic-abdominal aortic aneurysms
      treatment (hybrid procedures) and allowed to get better results. 2. Clear
      advantage of hybrid procedures above classical Crawford's procedure is observed
      in type I and II of TAAA. 3. Mortality and morbidity rates recommend hybrid
      procedure in type I and II of TAAA. 4. Surgical results of classical and hybrid
      procedures in type III-V TAAA treatment are comparative, with indication on
      classical approach.

PMID- 22659356
TI  - Analysis of factors influencing patient satisfaction with hospital treatment at
      the surgical department.
AB  - THE AIM OF THE STUDY was to determine factors responsible for patient
      satisfaction after treatment at the surgical department. MATERIAL AND METHODS:
      The study was conducted in six health care units, which were divided into two
      groups: Group I: 3 hospitals with the number of beds exceeding 400, and Group II:
      3 hospitals with the number of beds below 400. The study group comprised 180
      patients, 30 from each of the hospitals. The authors' used the Servqual method
      and questionnaire with 30 questions relating to five areas characteristic of
      medical service. Apart from the above-mentioned we also took into consideration
      hospital personnel: their qualifications and salary, hospital equipment, patient
      hospitalization costs, and indicated by the patient--the reason for his/her
      satisfaction or dissatisfaction with hospitalization. Results were subject to
      statistical analysis. RESULTS: The results indicated that the factors pertaining
      to costs, especially those related to living conditions and also those related to
      empathy, personnel competence, and their communication with the patient had very
      significant influence on patient satisfaction with his/her hospitalization.
      Fulfilling the patient's needs considering the functional quality increases the
      patient's comfort, and as a consequence translates into satisfaction with the
      hospitalization. CONCLUSIONS: Considering both groups of hospitals the surgical
      departments did not entirely fulfill the patient's expectations, and there is a
      need for improvement in this area. The main reason for the negative feelings of
      patients included worse than expected living conditions, sporadic contact with
      physicians and lack of information concerning the course of therapy.

PMID- 22659357
TI  - Long-term results of breast reduction in female-to-male transsexuals.
AB  - Transsexualism is considered to be an extreme end in a large group of gender
      identity disorders. Two main types of transsexualism are identified: male-to
      female (MtF) and female-to-male (FtM). Transsexual persons have a feeling of
      being incarcerated in a foreign body and therefore they wish to change their sex
      by hormone therapy and surgical treatment. Breast reduction usually is the first
      procedure in the process of surgical reassignment in FtM transsexual persons. THE
      AIM OF THIS STUDY was to evaluate the long-term results of breast reduction in
      FtM transsexual persons, taking into account breast size and surgical technique.
      The doctors' and patients' opinions about the results were also compared.
      MATERIAL AND METHODS: The study was carried out in a group of 98 FtM transsexual
      persons treated at the Department of Plastic, Reconstructive and Aesthetic
      Surgery. Evaluation of the long-term results of breast reduction was performed
      based on clinical examination done by the doctors and a questionnaire filled in
      by the patients and the surgeons. RESULTS: Good results of breast reduction were
      achieved in more than 60% of the examined patients operated on mainly by Webster
      technique. CONCLUSIONS: Clinical examination of the long-term results of breast
      reduction in FtM transsexual persons revealed good aesthetic effects. The
      doctors' and the patients' opinions were similar.

PMID- 22659358
TI  - Endoscopic ultrasonography (EUS) in preoperative staging of gastric cancer-
      demand and reality.
AB  - Exact pretherapeutic staging is considered to be essential for decision-making in
      the therapeutic algorithm of gastric cancer. THE AIM OF THE STUDY was to
      characterize the role and value of EUS in the diagnostic and therapeutic
      management of gastric cancer in daily surgical practice. MATERIAL AND METHODS:
      Thousand one hundred thirty nine patients with primary gastric cancer from 80
      hospitals of each profile of care were enrolled in this systematic clinical
      prospective multicenter observational study over a time period of 12 months. The
      characteristics of the diagnostic management, in particular, of EUS were
      documented. The preoperative EUS findings were compared with the T stage (T1 to
      T4) and the N category (N+ or N-) revealed by the histopathologic investigation
      of the surgical specimen. By the mean of chi2 test, the impact of EUS on the
      therapeutic decision-making was determined. RESULTS: Pretherapeutic EUS was only
      performed in 27.4% (n=312) of all patients. Overall, the diagnostic accuracy for
      the T stage was 42.6% in average. The subgroup analysis showed the following
      results: T1, 31.5%; T2, 42.6%; T3, 65.2%; T4, 17.6%. The correct predictive value
      of the N category was 71.3% reaching a sensitivity of 69.7% and a specificity of
      73.3%. Overstaging was observed in 45.8%, understaging in only 10.8%. Additional
      diagnostic information by EUS was only provided in 4.7% of subjects. CONCLUSIONS:
      The present study indicates the variability, limited reliability and only
      moderate acceptance of EUS in diagnosing gastric cancer in daily practice. In
      particular, the prediction of the T stage does not reach the data reported in the
      literature, which were mostly achieved in specific EUS studies.

PMID- 22659359
TI  - Critical upper limb ischemia caused by initially undiagnosed thoracic outlet
      syndrome--case report.
AB  - A case of a progressive ischemia of the right upper extremity in a 57-year-old
      male caused by primarily undiagnosed compression of a subclavian artery by an
      accessory cervical rib is presented. Critical limb ischemia persisting for 7
      years despite conservative treatment and a thrombectomy of upper extremity
      arteries and thoracic sympathectomy, led to a loss of three fingers and
      development of a non-healing ulceration of right upper extremity. Eventually a
      cervical rib resection together with a subclavio-brachial venous bypass graft
      permanently reversed the critical limb ischemia and allowed the ulceration to
      heal. The presented case underscores the importance of an early surgical
      intervention in patients with upper limb ischemia and anatomic abnormalities in a
      thoracic outlet.

PMID- 22659360
TI  - Gastrojejunocolic fistula in a 49 year-old male.
AB  - Gastrojejunocolic fistula is an unusual finding in patients with colon neoplams
      because long evolution time is required for its appearance. The methods of
      diagnosis have been and continue under discussion, being the barium enema the
      most accepted nowadays. Gastrocolic fistula is characterized by a declining
      incidence due to the new methods of diagnosis. An early detection of the tumour
      is completely necessary to prevent complications like fistulas or malnutrition.
      We present a case report of gastrojejunocolic fistula in a 49 year-old patient
      with colon carcinoma.

PMID- 22659361
TI  - The role of tissue engineering in the treatment of burn wounds.

PMID- 22659363
TI  - Stress-strain analysis for evaluating the effect of the orientation of dentin
      tubules on their mechanical properties and deformation behavior.
AB  - A model whose porosity does not vary with compression depth is developed for
      evaluating the mechanical properties of dentin tubules with various orientation
      angles from micro-pillar nanocompression tests. Experimental results for a range
      of loading rates indicate that the yielding parameters and the elastic modulus
      are little affected by the creep behavior. For a given compression depth, the
      hardness, elastic modulus, and yielding strength decrease with increasing
      orientation angle of dentin. The mechanical properties obtained using the
      proposed model are consistent with the reported data, and are actually more
      precise since they consider the orientation angle. The proposed testing method
      can be applied to materials that yield a negative value of the elastic modulus
      due to creep behavior.

PMID- 22659362
TI  - Identification of the Ah-receptor structural determinants for ligand preferences.
AB  - The aryl hydrocarbon receptor (AHR) is a transcription factor that responds to
      diverse ligands and plays a critical role in toxicology, immune function, and
      cardiovascular physiology. The structural basis of the AHR for ligand promiscuity
      and preferences is critical for understanding AHR function. Based on the
      structure of a closely related protein HIF2alpha, we modeled the AHR ligand
      binding domain (LBD) bound to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and
      benzo(a)pyrene (BaP) and identified residues that control ligand preferences by
      shape and H-bond potential. Mutations to these residues, particularly Q377 and
      G298, resulted in robust and opposite changes in the potency of TCDD and BaP and
      up to a 20-fold change in the ratio of TCDD/BaP efficacy. The model also revealed
      a flexible "belt" structure; molecular dynamic (MD) simulation suggested that the
      "belt" and several other structural elements in the AHR-LBD are more flexible
      than HIF2alpha and likely contribute to ligand promiscuity. Molecular docking of
      TCDD congeners to a model of human AHR-LBD ranks their binding affinity similar
      to experimental ranking of their toxicity. Our study reveals key structural basis
      for prediction of toxicity and understanding the AHR signaling through diverse
      ligands.

PMID- 22659364
TI  - An anisotropic inelastic constitutive model to describe stress softening and
      permanent deformation in arterial tissue.
AB  - Inelastic phenomena such as softening and unrecoverable inelastic strains induced
      by loading have been observed experimentally in soft tissues such as arteries.
      These phenomena need to be accounted for in constitutive models of arterial
      tissue so that computational models can accurately predict the outcomes of
      interventional procedures such as balloon angioplasty and stenting that involve
      non-physiological loading of the tissue. In this study, a novel constitutive
      model is described that accounts for inelastic effects such as Mullins-type
      softening and permanent set in a fibre reinforced tissue. The evolution of
      inelasticity is governed by a set of internal variables. Softening is introduced
      through a typical continuum damage mechanics approach, while the inelastic
      residual strains are introduced through an additive split in the stress tensor.
      Numerical simulations of aorta and carotid arterial tissue subjected to uniaxial
      testing in the longitudinal, circumferential and axial directions are used to
      demonstrate the model's ability to reproduce the anisotropic inelastic behaviour
      of the tissue. Material parameters derived from best-fits to experimental data
      are provided to describe these inelastic effects for both aortic and carotid
      tissue.

PMID- 22659365
TI  - New insights into hard phases of CoCrMo metal-on-metal hip replacements.
AB  - The microstructural and mechanical properties of the hard phases in CoCrMo
      prosthetic alloys in both cast and wrought conditions were examined using
      transmission electron microscopy and nanoindentation. Besides the known carbides
      of M(23)C(6)-type (M=Cr, Mo, Co) and M(6)C-type which are formed by either
      eutectic solidification or precipitation, a new mixed-phase hard constituent has
      been found in the cast alloys, which is composed of ~100 nm fine grains. The
      nanosized grains were identified to be mostly of M(23)C(6) type using nano-beam
      precession electron diffraction, and the chemical composition varied from grain
      to grain being either Cr- or Co-rich. In contrast, the carbides within the
      wrought alloy having the same M(23)C(6) structure were homogeneous, which can be
      attributed to the repeated heating and deformation steps. Nanoindentation
      measurements showed that the hardness of the hard phase mixture in the cast
      specimen was ~15.7 GPa, while the M(23)C(6) carbides in the wrought alloy were
      twice as hard (~30.7 GPa). The origin of the nanostructured hard phase mixture
      was found to be related to slow cooling during casting. Mixed hard phases were
      produced at a cooling rate of 0.2  degrees C/s, whereas single phase carbides
      were formed at a cooling rate of 50  degrees C/s. This is consistent with
      sluggish kinetics and rationalizes different and partly conflicting
      microstructural results in the literature, and could be a source of variations in
      the performance of prosthetic devices in-vivo.

PMID- 22659366
TI  - A three-scale finite element investigation into the effects of tissue
      mineralisation and lamellar organisation in human cortical and trabecular bone.
AB  - Bone is an exceptional material that is lightweight for efficient movement but
      also exhibits excellent strength and stiffness imparted by a composite material
      of organic proteins and mineral crystals that are intricately organised on many
      scales. Experimental and computational studies have sought to understand the role
      of bone composition and organisation in regulating the biomechanical behaviour of
      bone. However, due to the complex hierarchical arrangement of the constituent
      materials, the reported experimental values for the elastic modulus of trabecular
      and cortical tissue have conflicted greatly. Furthermore, finite element studies
      of bone have largely made the simplifying assumption that material behaviour was
      homogeneous or that tissue variability only occurred at the microscale, based on
      grey values from micro-CT scans. Thus, it remains that the precise role of
      nanoscale tissue constituents and microscale tissue organisation is not fully
      understood and more importantly that these have never been incorporated together
      to predict bone fracture or implant outcome in a multiscale finite element
      framework. In this paper, a three-scale finite element homogenisation scheme is
      presented which enables the prediction of homogenised effective properties of
      tissue level bone from its fundamental nanoscale constituents of hydroxyapatite
      mineral crystals and organic collagen proteins. Two independent homogenisation
      steps are performed on representative volume elements which describe the local
      morphological arrangement of both the nanostructural and microstructural levels.
      This three-scale homogenisation scheme predicts differences in the tissue level
      properties of bone as a function of mineral volume fraction, mineral aspect ratio
      and lamellar orientation. These parameters were chosen to lie within normal
      tissue ranges derived from experimental studies, and it was found that the
      predicted stiffness properties at the lamellar level correlate well with
      experimental nanoindentation results from cortical and trabecular bone.
      Furthermore, these studies show variations in mineral volume fraction, mineral
      crystal size and lamellar orientation could be responsible for previous
      discrepancies in experimental reports of tissue moduli. We propose that this
      novel multiscale modelling approach can provide a more accurate description of
      bone tissue properties in continuum/organ level finite element models by
      incorporating information regarding tissue structure and composition from
      advanced imaging techniques. This approach could thereby provide a preclinical
      tool to predict bone mechanics following prosthetic implantation or bone fracture
      during disease.

PMID- 22659367
TI  - Viscoelastic characterization of rat cerebral cortex and type I collagen
      scaffolds for central nervous system tissue engineering.
AB  - In the field of tissue engineering and regenerative medicine for the central
      nervous system, therapeutic strategies may involve implantation of biomaterial
      scaffolds into the brain. An understanding of the relationship between the brain
      and the scaffold mechanical properties can help in the selection of a safe and
      effective biomaterial. This research demonstrates the use of indentation testing
      along with viscoelastic modeling to characterize and compare mechanical
      properties of in situ rat cerebral cortex and collagen scaffolds of varying
      collagen concentration. The stress-relaxation solution for indentation of a
      viscoelastic material was derived based on a five-element Maxwell model and use
      of the correspondence principle. Applying the model to experimental stress
      relaxation data, the brain was characterized by three shear moduli G(1)=1.6+/
      0.10 kPa, G(2)=2.0+/-0.15 kPa, G(3)=1.8+/-0.20 kPa, and two viscosities
      eta(2)=11.0 +/- 0.44 kPa?s, eta(3)=148.7 +/- 6.70 kPa?s, with corresponding
      relaxation time constants tau(1)=5.7+/-0.3 s and tau(2)=88.4 +/- 7.6 s. The brain
      showed average relaxation of 74% from its peak force during loading to an
      approximately asymptotic force over a 5 minute hold at constant displacement.
      Collagen scaffolds generally showed increasing trends in the shear moduli,
      viscosities, and percentage relaxation with increasing collagen concentration.
      While the brain had similar stiffness to the 1.0% collagen scaffold during the
      loading phase, the brain's relaxation behavior was distinct from all of the
      scaffolds. Similarities and differences between the mechanical behavior of the
      brain and collagen scaffolds of varying collagen concentration are discussed in
      relation to application of biomaterials for regenerative medicine.

PMID- 22659368
TI  - Branching toughens fibrous networks.
AB  - Fibrous collagenous networks are not only stiff but also tough, due to their
      complex microstructures. This stiff yet tough behavior is desirable for both
      medical and military applications but it is difficult to reproduce in engineering
      materials. While the nonlinear hyperelastic behavior of fibrous networks has been
      extensively studied, the understanding of toughness is still incomplete. Here, we
      identify a microstructure mimicking the branched bundles of a natural type I
      collagen network, in which partially cross-linked long fibers give rise to novel
      combinations of stiffness and toughness. Finite element analysis shows that the
      stiffness of fully cross-linked fibrous networks is amplified by increasing the
      fibril length and cross-link density. However, a trade-off of such stiff networks
      is reduced toughness. By having partially cross-linked networks with long
      fibrils, the networks have comparable stiffness and improved toughness as
      compared to the fully cross-linked networks. Further, the partially cross-linked
      networks avoid the formation of kinks, which cause fibril rupture during
      deformation. As a result, the branching allows the networks to have stiff yet
      tough behavior.

PMID- 22659369
TI  - Microstructure, hardness, corrosion resistance and porcelain shear bond strength
      comparison between cast and hot pressed CoCrMo alloy for metal-ceramic dental
      restorations.
AB  - OBJECTIVES: The purpose of this study was to compare the microstructure,
      hardness, corrosion resistance and metal-porcelain bond strength of a CoCrMo
      dental alloy obtained by two routes, cast and hot pressing. METHODS: CoCrMo alloy
      substrates were obtained by casting and hot pressing. Substrates' microstructure
      was examined by the means of Optical Microscopy (OM) and by Scanning Electron
      Microscope (SEM) and Energy Dispersive X-ray Spectroscopy (EDS). Hardness tests
      were performed in a microhardness indenter. The electrochemical behavior of
      substrates was investigated through potentiodynamic tests in a saline solution
      (8g NaCl/L). Substrates were bonded to dental porcelain and metal-porcelain bond
      strength was assessed by the means of a shear test performed in a universal test
      machine (crosshead speed: 0.5 mm/min) until fracture. Fractured surfaces as well
      as undestroyed interface specimens were examined with Stereomicroscopy and SEM
      EDS. Data was analyzed with Shapiro-Wilk test to test the assumption of
      normality. The t-test (p<0.05) was used to compare shear bond strength results.
      RESULTS: Cast specimens exhibited dendritic microstructures whereas hot pressed
      specimens exhibited a typical globular microstructure with a second phase spread
      through the matrix. The hardness registered for hot pressed substrates was
      greater than that of cast specimens, 438+/-24HV/1 and 324+/-8HV/1, respectively.
      Hot pressed substrates showed better corrosion properties than cast ones, i.e.
      higher OCP; higher corrosion potential (E(corr)) and lower current densities
      (i(corr)). No significant difference was found (p<0.05) in metal-ceramic bond
      strength between cast (116.5+/-6.9 MPa) and hot pressed (114.2+/-11.9 MPa)
      substrates. The failure type analysis revealed an adhesive failure for all
      specimens. SIGNIFICANCE: Hot pressed products arise as an alternative to cast
      products in dental prosthetics, as they impart enhanced mechanical and
      electrochemical properties to prostheses without compromising the metal-ceramic
      bond strength.

PMID- 22659370
TI  - Layer-specific damage experiments and modeling of human thoracic and abdominal
      aortas with non-atherosclerotic intimal thickening.
AB  - Many treatments for cardiovascular diseases include an endovascular insertion of
      stents or stent grafts into arteries, a procedure which may cause high tissue
      stresses and even damage in the arterial wall. In order to study such problems by
      using finite element methods, both appropriate constitutive models and
      experimental data on human tissue samples are required. Layer-specific
      experimental data for human tissue tested up to the supra-physiological loading
      range are rare in the literature. In this study, intact and layer-separated
      experimental data from uniaxial extension tests are presented for human thoracic
      and abdominal aortas with non-atherosclerotic intimal thickening undergoing supra
      physiological loading. A novel pseudo-elastic damage model, proposed to describe
      discontinuous softening in aortic arterial tissues, is fit to the obtained
      experimental data. Fitting of the model with and without consideration of damage
      accumulation in the non-collagenous matrix material reveals that tissue damage is
      primarily related to the collagen fiber fabric. By employing the fit model, the
      effect of aortic tissue pre-conditioning on the material parameters from the
      resulting data fits is evaluated. Histological examination of the collagen fibers
      under different applied stretches is used to gain more insights into the
      structural changes of the tissue under supra-physiological loading.

PMID- 22659371
TI  - Arterial clamping: finite element simulation and in vivo validation.
AB  - Commonly used techniques in cardiovascular interventions such as arterial
      clamping always entail a certain degree of unavoidable iatrogenic tissue damage.
      Therefore, studies have been directed towards the decrease of undesired
      intraoperative trauma, for example, through the design of less traumatic surgical
      instruments. Obviously, the effectiveness of new clamp designs and techniques
      depends on how well damage mechanisms are understood and how accurate thresholds
      for safe tissue loading can be set. This information can in part be derived from
      reliable finite element simulations. This study is the first to describe a finite
      element simulation of the clamping of a rat abdominal aorta with occlusion and in
      vivo validation. Material nonlinearity, large deformations, contact interactions
      and residual strains are hereby taken into account. The mechanical parameters of
      the model are derived from inflation experiments. The effect of the residual
      strains, different clamp geometries as well as the effect of variations in
      material properties are studied. In all simulations, stress concentrations in
      different regions of the tissue are noticed, especially for a corrugated clamp
      design. This shows the importance of finite element modeling in understanding the
      relation between mechanical loading and damage mechanisms. The inclusion of
      residual strains has its effect not only in the physiological loading regime, but
      also during clamping. Just as in the physiologic regime, it lowers the stress
      gradients through the wall thickness. Varying the material properties with the
      measured standard deviation between specimens leads to an average change of +/
      17% in the maximum and minimum principal stresses. Finally, the model is
      validated with an in vivo clamping experiment on a Wistar rat in which the
      clamping force was measured, showing good correspondence with the modeled
      clamping force.

PMID- 22659372
TI  - Determination of permeability coefficients of ophthalmic drugs through different
      layers of porcine, rabbit and bovine eyes.
AB  - To treat ophthalmic diseases like glaucoma or inflammatory disorders topically
      applied ophthalmic formulations such as eye drops are usually used. In addition,
      novel ophthalmic implants releasing drug substances locally into different parts
      of the eye are available today. In the work presented here, the permeability
      coefficients of selected drugs (ciprofloxacin hydrochloride, lidocaine
      hydrochloride, timolol maleate) for ophthalmic tissues were determined using side
      by-side diffusion chambers (so-called Ussing chambers). Sclera, conjunctiva,
      cornea, choroidea-retina-complex and a complex of conjunctiva-sclera-choroidea
      retina were excised from fresh porcine, rabbit and bovine eyes. In the porcine
      eye tissues the highest P(app) values were obtained for conjunctiva with the
      exception of lidocaine. Therefore, it can be estimated that a certain amount of
      drug diffuses or is transported through conjunctiva after application. The P(app)
      values for sclera were also higher than those for cornea and even more, the
      surface area of sclera which is available for drug absorption is much larger than
      that of cornea when applying an implant. The obtained permeability coefficients
      for sclera and conjunctiva indicate that the administration of periocular
      implants can be an alternative to topically applied formulations. The complexes
      of the tissues were a significantly (p<0.01) stronger barrier to the investigated
      substances than the separated tissues. Distinct differences in permeability
      coefficients between the investigated animal tissues were observed. Overall the
      highest P(app) values for all mounted tissues were obtained with the rabbit,
      followed by porcine and bovine eyes. Because of these distinct interspecies
      differences one must be very careful when selecting the proper animal model for
      the permeability experiments.

PMID- 22659373
TI  - LDL S-homocysteinylation decrease in chronic kidney disease patients undergone
      lipid lowering therapy.
AB  - The dyslipidemia control through lipid lowering therapy is one of the targets for
      the treatment of CKD. By this pilot study we aimed to evaluate the effect of
      hypolipidemic drugs on the levels of low molecular weight (LMW) thiols bound to
      LDL in nephropatic patients. We enrolled thirty CKD randomized to receive three
      different hypolipidemic regimens: simvastatin alone (40 mg/day) or
      ezetimibe/simvastatin combined therapy (10/20 or 10/40 mg/day). LMW thiols in
      their reduced and total form, oxidative stress indices as malondialdehyde and
      allantoin/uric acid ratio were evaluated. LDL thiolation decreased in all treated
      patients, but a greater efficacy was attained from a combined therapy with a
      higher simvastatin dose, by which a 31% decrease of all S-bound thiols was
      reached after 1 year of therapy. In particular, in this patients group the
      reduction of apoB-Hcy was greater than 40%. The concomitant decrease of the
      oxidative stress indices during the therapy brings to the hypothesis that
      decreased levels of protein bound thiols may be a consequence of oxidative stress
      improvement. Therefore lipid lowering therapy may have beneficial effects also
      through the reduction of LDL-S-homocysteinylation that has been reported to have
      antiangiogenic and proatherogenic effect on endothelial vascular cells.

PMID- 22659374
TI  - Consumption of a high-fat diet during pregnancy decreases the activity of
      cytochrome P450 3a in the livers of offspring.
AB  - Recent studies have reported that a high-fat diet during pregnancy exerts various
      effects on the foetus and newborn. The purpose of this study was to clarify the
      effects of a high-fat diet during pregnancy on the activity of hepatic cytochrome
      P450 (Cyp) 3a in offspring in mice. The protein expression level and activity of
      Cyp3a in the livers of 6-week-old mice born to mothers that were given a high-fat
      diet during pregnancy (HF group) decreased significantly compared with the
      Control group. Triazolam, which is a substrate of Cyp3a, was intraperitoneally
      administered to the mice in the HF group. Compared with the Control group, an
      increase in the area under the plasma concentration-time curve and a decrease in
      total clearance were observed in the HF group. The hepatic constitutive
      androstane receptor (CAR) mRNA expression level in the HF group was significantly
      lower than that in the Control group. An increase in phosphorylation of
      extracellular signal-regulated kinase (ERK) was also observed in the HF group.
      The results of this study revealed that a high-fat diet during pregnancy causes
      an increase in ERK phosphorylation and a decrease in the expression level of CAR
      in the livers of offspring, which leads to decreased Cyp3a expression and
      activity. The results suggest that individual differences in pharmacokinetics may
      not only be expressed by genetic predisposition but also by a mother's living
      environment during pregnancy.

PMID- 22659376
TI  - WITHDRAWN: Hsp70 overexpression coordinately regulates myocardial hypertrophy,
      fibrosis and contractile function in 5-HT(2B) blockade mediated anti-hypertrophic
      effect.
AB  - This article has been withdrawn at the request of the editors. 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- 22659375
TI  - QSAR, docking and in vivo studies for immunomodulatory activity of isolated
      triterpenoids from Eucalyptus tereticornis and Gentiana kurroo.
AB  - Two triterpenoids ursolic acid (1) and lupeol (2) isolated and characterized from
      Eucalyptus tereticornis and Gentiana kurroo were subjected to in silico QSAR
      modeling and docking studies and later the predicted results were confirmed
      through in vivo experiments. QSAR modeling results showed that both the
      triterpenoids possess immunomodulatory and anti-inflammatory activity comparable
      to boswellic and cichoric acids, but were less active than levamisol. Docking
      results suggested that both the triterpenoids (1 and 2) showed immune modulatory
      and anti-inflammatory activity due to high binding affinity to human receptors
      viz., NF-kappaB p52 (-50.549 kcal/mol), tumor necrosis factor (TNF-alpha) (
      47.632 kcal/mol), nuclear factor NF-Kappa-B P50 (-16.798 kcal/mol) and
      cyclooxygenase-2 (-55.244 kcal/mol). Further both the triterpenoids (1 and 2)
      were subjected to in vivo immunomodulatory activity in female Swiss albino mice.
      The experimental mice were divided into nine groups, each comprised of six mice.
      These received oral treatment for a period of 28 days. The triterpenoids (1 and
      2) showed significant increased in humoral immune function, but no significant
      changes were observed in cell mediated immune response and hematological
      parameters. The in silico and in vivo experimental data suggested that both the
      triterpenoids 1 and 2 may be considered as potential immunomodulatory drug-like
      molecules.

PMID- 22659378
TI  - Dobrava-Belgrade virus: phylogeny, epidemiology, disease.
AB  - Dobrava-Belgrade virus (DOBV) is an Old World hantavirus that causes hemorrhagic
      fever with renal syndrome in humans. With a case fatality rate up to 12%, DOBV
      infection is the most life-threatening hantavirus disease in Europe. The virus
      was initially identified in the Balkans, but the discovery of new endemic foci
      have expanded its recognized geographic range. The recent description of novel
      genetic variants with different degrees of pathogenicity have complicated its
      taxonomic analysis. The original rodent host of DOBV is Apodemus flavicollis,
      however additional Apodemus species, such Apodemus agrarius and Apodemus
      ponticus, have been found to serve as hosts of the various DOBV genotypes. The
      complex evolution and genetic diversity of the virus are still under
      investigation. The present review aims to provide an update on the phylogeny of
      DOBV and the epidemiology of infection in rodents and humans; to describe the
      clinical characteristics of the disease; to present current knowledge about
      laboratory diagnosis, treatment and prevention; discuss the current state of the
      art in antiviral drug and vaccine development.

PMID- 22659377
TI  - The serotonin transporter gene polymorphism (5HTTLPR) moderates the effect of
      adolescent environmental conditions on self-esteem in young adulthood: a
      structural equation modeling approach.
AB  - Here we examine the effects of both self-reported and independent observer
      reported environmental risk indices, the serotonin transporter gene promoter
      (5HTTLPR) polymorphism, and their interaction on self-esteem. This trait was
      assessed during early and mid adolescence (mean age=14 and 16.5, respectively)
      and young adulthood (mean age=21.8) in a prospective cohort of 1214 unrelated
      participants in the Longitudinal Study of Adolescent Health (Add Health). Using
      structural equation modeling we identified a gene-environment (G*E) interaction
      using observer-report but not self-report measures of environmental stress
      exposure during adolescence: 5HTTLPR genotype and observer-reports of home and
      neighborhood quality (HNQ) during adolescence interacted to predict self-esteem
      levels in young adulthood (p<.004). Carriers of the s allele who lived in poor
      HNQ conditions during adolescence reported lower self-esteem in young adulthood
      than those with a good HNQ during adolescence. In contrast, among individuals
      with the l/l genotype, adolescent HNQ did not predict adulthood self-esteem.
      Genes may moderate the effect of adolescent environmental conditions on adulthood
      self-esteem.

PMID- 22659379
TI  - Preparation and stability study of norfloxacin-loaded solid lipid nanoparticle
      suspensions.
AB  - This work aims to develop norfloxacin-loaded solid lipid nanoparticle (NFX-SLN)
      suspensions as a novel formulation. NFX-SLN suspensions were prepared by hot
      homogenization and ultrasonic technique. The stability of the suspensions was
      studied after stored at 4 degrees C and room temperature from 3 to 9 months. The
      physicochemical characteristics of the NFX-SLN, in vitro release patterns, in
      vitro antibacterial activity and in vivo therapeutic efficacy in mice after
      infection with Escherichia coli were conducted and used to evaluate the stability
      of the suspension. The results showed that the mean diameter (MD), polydispersity
      index (PDI), zeta potential (ZP) and loading capacity (LC) of nanoparticles were
      250+/-5 nm, 0.256+/-0.065, -31.1+/-1.85 mV and 9.63+/-0.16%, respectively. After
      9 months of storage at 4 degrees C, the NFX-SLN showed no significant changes in
      MD, PDI and LC except a miner change in ZP. Moreover, the stored suspension
      displayed same sustained release patterns and in vitro sustained bactericidal
      activities as that of the fresh preparation. In vivo therapeutic results revealed
      that the stored suspension had similar enhanced therapeutic efficacy as the fresh
      preparation compared with native drug. At room temperature the formulation was
      stable for 3 months, but the LC, ZP and PDI changed and the suspension displayed
      accelerated release and weakened in vitro antibacterial activity after 6 months.
      These results demonstrate that NFX-SLN suspensions could be a promising
      formulation for enhanced pharmacological activity of norfloxacin and were stable
      at 4 degrees C and less stable at room temperature.

PMID- 22659380
TI  - Expression and purification of recombinant human tyrosine hydroxylase as a fusion
      protein in Escherichia coli.
AB  - Tyrosine hydroxylase is the rate-limiting step in the synthesis of dopamine and
      is tightly regulated. Previous studies have shown it to be covalently modified
      and potently inhibited by 3,4-dihydroxyphenylacetaldehyde (DOPAL), an endogenous
      neurotoxin via dopamine catabolism which is relevant to Parkinson's disease. In
      order to elucidate the mechanism of enzyme inhibition, a source of pure, active
      tyrosine hydroxylase was necessary. The cloning and novel purification of human
      recombinant TH from Escherichia coli is described here. This procedure led to the
      recovery of ~23 mg of pure, active and stable enzyme exhibiting a specific
      activity of ~17 nmol/min/mg. The enzyme produced with this procedure can be used
      to delineate the tyrosine hydroxylase inhibition by DOPAL and its relationship to
      Parkinson's disease. This procedure improves upon previous methods because the
      fusion protein gives rise to high expression and convenient affinity-capture, and
      the cleaved and highly purified hTH makes the product useful for a wider variety
      of applications.

PMID- 22659381
TI  - PPAR gamma activation protects the brain against microvascular dysfunction in
      sepsis.
AB  - Sepsis is a severe disorder characterized by systemic inflammatory responses in
      the presence of an infection and may progress to multiple organ dysfunction and
      death. Alterations in cerebral microcirculation fulfill a crucial role in the
      pathogenesis of severe sepsis, and include a decrease in capillary density and
      disturbances in leukocyte movement along capillaries. Nevertheless, the
      mechanisms involved in sepsis-associated cerebral microcirculatory alterations
      have so far not been defined. We investigated the effect of the peroxisome
      proliferator-activated receptor gamma (PPARgamma) selective agonist rosiglitazone
      on leukocyte/endothelial cell interaction and functional capillary density in the
      brain in the cecal ligation and puncture (CLP) model of sepsis. Anti-inflammatory
      effects of rosiglitazone on the cerebral microcirculation were marked. Functional
      capillary density increased and leukocyte rolling and adhesion were decreased in
      animals submitted to CLP and treated with rosiglitazone. Our data provide
      evidence for involvement of PPARgamma activation in leukocyte-endothelium
      interactions and alterations in capillary density. Improved cerebral perfusion in
      animals treated with rosiglitazone, suggests that PPARgamma activation is
      protective against cerebral microvascular dysfunction in sepsis.

PMID- 22659382
TI  - Demand characteristics, pre-test attitudes and time-on-task trends in the effects
      of chewing gum on attention and reported mood in healthy volunteers.
AB  - Previous research has indicated that chewing gum enhances reported alertness, but
      has variable effects on attention. Demand characteristics may explain these
      effects. The current study investigated the effects of gum and demand
      characteristics on attention and reported mood over time. Participants completed
      measures of mood and attention, with and without chewing gum. To manipulate
      demand characteristics, they were told that the hypothesised effect of gum was
      either positive or negative, or no hypothesis was mentioned. Attitudes towards
      gum were assessed pre- and post-manipulation. Gum increased reported alertness;
      this effect was only significant for positive and neutral demand characteristics.
      Vigilance accuracy was reduced for chewing gum, but only in the fourth minute of
      the task, and gum reduced focussed attention accuracy, but only for the first 64
      trials. Demand characteristics did not moderate time-on-task effects. Gum
      improved selective attention. A positive effect on response organisation was
      observed; this was significant when demand characteristics and pre-test attitudes
      to gum were both negative. The results suggest that demand characteristics
      moderate effects on self-reported alertness and response organisation, but cannot
      explain time-on-task effects or variable main effects on other aspects of
      attention.

PMID- 22659383
TI  - Proteomic analysis of the reproductive tract fluids from tropically-adapted Santa
      Ines rams.
AB  - The present study is focused on the proteome of reproductive tract fluids from
      tropically-adapted Santa Ines rams. Seminal plasma, cauda epididymal (CEF) and
      vesicular gland fluid (VGF) proteins were analyzed by 2-D electrophoresis and
      mass spectrometry. Seminal plasma maps contained 302 +/- 16 spots, within the 4-7
      pH range. From these maps, 73 spots were identified, corresponding to 41
      proteins. Ram Seminal Vesicle Proteins (RSVP) 14 and 22kDa and bodhesins 1 and 2
      represented the most abundant seminal components. Other seminal proteins included
      clusterin, angiotensin-converting enzyme, matrix metalloproteinase-2, tissue
      inhibitor of metalloproteinase-2, plasma glutamate carboxypeptidase, albumin,
      lactoferrin, alpha enolase, peroxiredoxin, leucine aminopeptidase, beta
      galactosidase, among others. Later, seminal plasma gels were run within narrow pH
      intervals (3.9-5.1; 4.7-5.9; 5.5-6.7), allowing the additional identification of
      21 proteins not detected in 4-7 pH maps. Major proteins of CEF and VGF were
      albumin and transferrin, and RSVPs, respectively. Western blots confirmed that
      RSVPs were mainly present in VGF while bodhesins, in VGF and CEF. Based on RT
      PCR, RSVP and bodhesin genes were primarily expressed in the vesicular glands. In
      summary, the reproductive tract fluids of Brazilian hairy rams contain several
      categories of proteins, with potential roles in sperm protection, capacitation,
      acrosome reaction and sperm-oocyte interaction.

PMID- 22659384
TI  - Alteration of protein glycosylation in human hepatic stellate cells activated
      with transforming growth factor-beta1.
AB  - Although aberrant glycosylation of human glycoproteins is related to liver
      fibrosis that results from chronic damage to the liver in conjunction with the
      activation of hepatic stellate cells (HSCs), little is known about the precision
      alteration of protein glycosylation referred to the activation of HSCs by
      transforming growth factor-beta1 (TGF-beta1). The human HSCs, LX-2 were activated
      by TGF-beta1. The lectin microarrays were used to probe the alteration of protein
      glycosylation in the activated HSCs compared with the quiescent HSCs. Lectin
      histochemistry was used to further validate the lectin binding profiles and
      assess the distribution of glycosidic residues in cells. As a result, 14 lectins
      (e. g. AAL, PHA-E, ECA and ConA) showed increased signal while 7 lectins (e. g.
      UEA-I and GNA) showed decreased signal in the activated LX-2 compared with the
      quiescent LX-2. Meanwhile, AAL, PHA-E and ECA staining showed moderate binding to
      the cytoplasma membrane in the quiescent LX-2, and the binding intensified in the
      same regions of the activated LX-2. In conclusion, the precision alteration of
      protein glycosylation related to the activation of the HSCs may provide useful
      information to find new molecular mechanism of HSC activation and antifibrotic
      therapeutic strategies.

PMID- 22659385
TI  - Separate diagnoses of Hodgkin lymphoma and non-Hodgkin lymphoma in an individual
      patient might not signify a common clonal origin.
AB  - Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) have traditionally been
      considered as two distinct entities. However, there are rare reports of patients
      that, over time, develop both diseases. It remains unresolved whether the origin
      of the two diseases is from the same clone. In this study, we attempted to
      retrospectively investigate the clinical and molecular aspects of patients who
      developed both lymphomas. The rearranged immunoglobulin heavy-chain variable
      region genes from both diagnoses were compared to each other. Twenty-six patients
      presented with both diagnoses. Twelve had HL as the primary disorder ("HL first"
      group) and the majority of these (75%) presented with aggressive lymphoma as the
      second lymphoma. In contrast, in the 11 patients for whom NHL was the primary
      disorder ("NHL first" group), this was usually (82%) of low-grade histology.
      Three patients were diagnosed concurrently with both diseases. Mean age at first
      diagnosis was higher (p = 0.037) in the NHL first group (56.1 years) than in the
      HL first group (40 years). Mean time between diagnoses was longer (p = 0.026) in
      the HL first group (9 years) than in the NHL first group (5 years). For 11
      patients, diagnostic samples were available for molecular analyses from both
      diagnoses of HL and NHL. In 6 of these 11 patients, gene rearrangement studies
      were informative. No patient had the same gene rearrangement identified in both
      diseases. It seems that development of HL and NHL in one patient, at different
      time points, reflects, in many cases, separate biologic diseases.

PMID- 22659386
TI  - Endothelialization and altered hematopoiesis by persistent Etv2 expression in
      mice.
AB  - Etv2 is a master gene for the commitment of hematopoietic/endothelial cells and
      is a potent inducer of endothelial/hematopoietic cells from embryonic stem cells.
      Etv2 is highly expressed in endothelial/hematopoietic precursors but is
      downregulated when they are differentiated, indicating that Etv2 should have
      transient but not constitutive function. However, relatively little attention has
      been paid to the importance of transient Etv2 expression. To determine whether
      transient Etv2 expression is essential to normal development and cell
      differentiation, we generated mice that constitutively express Etv2 from a Cre
      activatable ROSA26 locus in endothelial/hematopoietic, somite, or neuronal
      lineages. Constitutive Etv2 expression caused profound phenotypes in
      hematopoietic/endothelial cells, with little effect on somite or neuronal
      lineages. In hematopoietic/endothelial lineages, constitutive Etv2 expression
      induced by Tie-2 Cre transgene caused abnormal yolk sac vasculature. Prolonged
      vascular endothelial cadherin expression and decreased B lymphopoiesis were
      observed in Etv2 expressing vascular endothelial cadherin(+)/CD45(+) cells,
      indicating that Etv2 forces endothelial program on hematopoietic cells. Etv2
      expression in adult hematopoietic cells by Vav-iCre transgene also conferred an
      endothelial phenotype on hematopoietic stem cells and suppressed hematopoiesis,
      with erythropoiesis severely affected. We conclude that constitutive Etv2
      expression perturbs vascular development and hematopoiesis. While promoting
      hematopoiesis/vasculogenesis, Etv2 expression should be tightly regulated to
      achieve normal vascular development and hematopoiesis.

PMID- 22659387
TI  - Phosphoprotein profiling predicts response to tyrosine kinase inhibitor therapy
      in chronic myeloid leukemia patients.
AB  - Tyrosine kinase inhibitors (TKIs) have dramatically improved treatment outcomes
      in chronic myeloid leukemia (CML), but a proportion of patients fail to achieve
      optimal molecular response. By using a phosphoproteomic approach, we aimed to
      discover aberrant signaling pathways and putative biomarkers in bone marrow
      samples of suboptimally responding patients, which could be used to guide
      treatment selection at the diagnosis. The study consisted of 20 chronic-phase CML
      patients (10 optimal and 10 suboptimal response patients based on 18 months
      European-Leukemia-Net criteria) and healthy bone marrow cells, and CML cell lines
      were used as controls. The phosphorylation profile of normal bone marrow cells
      diverged from CML patients expectedly but, interestingly, CML cell lines (such as
      K562) also showed marked difference with primary CML cells. Several
      phosphoproteins were elevated in suboptimal patients compared to optimal response
      group. Most prominent differences were seen in signal transducers and activators
      of transcription 5b, phospholipase C gamma-1, proline-rich tyrosine kinase 2,
      Hck, and Paxillin. These phosphoproteins were also increased in three additional
      nonresponder patients studied, but each of them also had unique phosphorylation
      patterns, such as highly active HSP27 protein in one patient. In conclusion,
      suboptimal imatinib response is related to increased phosphorylation of several
      proteins at diagnosis, which might guide the selection of TKI therapy.
      Furthermore, the activation of additional BCR-ABL-independent pathways in
      nonresponder patients (such as the anti-apoptotic HSP27 pathway) may reveal novel
      therapy targets.

PMID- 22659388
TI  - Gene expression profiling with principal component analysis depicts the
      biological continuum from essential thrombocythemia over polycythemia vera to
      myelofibrosis.
AB  - The recent discovery of the Janus activating kinase 2 V617F mutation in most
      patients with polycythemia vera (PV) and half of those with essential
      thrombocythemia (ET) and primary myelofibrosis (PMF) has favored the hypothesis
      of a biological continuum from ET over PV to PMF. We performed gene expression
      profiling of whole blood from control subjects (n = 21) and patients with ET (n =
      19), PV (n = 41), and PMF (n = 9) using DNA microarrays. Applying an unsupervised
      method, principal component analysis, to search for patterns in the data, we
      demonstrated a separation of the four groups with biological relevant overlaps
      between the different entities. Moreover, the analysis separates Janus activating
      kinase 2-negative ET patients from Janus activating kinase 2-positive ET
      patients. Functional annotation analysis demonstrates that clusters of gene
      ontology terms related to inflammation, immune system, apoptosis, RNA metabolism,
      and secretory system were the most significantly deregulated terms in the three
      different disease groups. Our results yield further support for the hypothesis of
      a biological continuum originating from ET over PV to PMF. Functional analysis
      suggests an important implication of these gene ontology clusters in the
      pathogenesis of these neoplasms and in disease evolution from ET over PV to PMF.

PMID- 22659389
TI  - A biomechanical role for perlecan in the pericellular matrix of articular
      cartilage.
AB  - Chondrocytes are surrounded by a narrow pericellular matrix (PCM) that is
      biochemically, structurally, and biomechanically distinct from the bulk
      extracellular matrix (ECM) of articular cartilage. While the PCM is often defined
      by the presence of type VI collagen, other macromolecules such as perlecan, a
      heparan sulfate (HS) proteoglycan, are also exclusively localized to the PCM in
      normal cartilage and likely contribute to PCM structural integrity and
      biomechanical properties. Though perlecan is essential for normal cartilage
      development, its exact role in the PCM is unknown. The objective of this study
      was to determine the biomechanical role of perlecan in the articular cartilage
      PCM in situ and its potential as a defining factor of the PCM. To this end,
      atomic force microscopy (AFM) stiffness mapping was combined with dual
      immunofluorescence labeling of cryosectioned porcine cartilage samples for type
      VI collagen and perlecan. While there was no difference in overall PCM mechanical
      properties between type VI collagen- and perlecan-based definitions of the PCM,
      within the PCM, interior regions containing both type VI collagen and perlecan
      exhibited lower elastic moduli than more peripheral regions rich in type VI
      collagen alone. Enzymatic removal of HS chains from perlecan with heparinase III
      increased PCM elastic moduli both overall and locally in interior regions rich in
      both perlecan and type VI collagen. Heparinase III digestion had no effect on ECM
      elastic moduli. Our findings provide new evidence for perlecan as a defining
      factor in both the biochemical and biomechanical properties of the PCM.

PMID- 22659391
TI  - Critical roles of acetylcholine and the muscarinic and nicotinic acetylcholine
      receptors in the regulation of immune function.
AB  - Lymphocytes express both muscarinic and nicotinic acetylcholine (ACh) receptors
      (mAChRs and nAChRs, respectively), and stimulation of mAChRs and nAChRs produces
      various biochemical and functional changes. Although it has been postulated that
      parasympathetic cholinergic nerves directly innervate immune cells, no evidence
      has supported this hypothesis. We measured ACh in the blood of various animal
      species and determined its localization in T cells using a sensitive and specific
      radioimmunoassay. Furthermore, we showed that T cells express choline
      acetyltransferase (ChAT), an ACh synthesizing enzyme. Immunological T cell
      activation enhances ACh synthesis through the up-regulation of ChAT expression,
      suggesting lymphocytic cholinergic activity is related to immunological activity.
      Most immune cells such as T cells, B cells, and monocytes express all five
      subtypes of mAChRs (M(1)-M(5)), and various subunits of the nAChR, such as
      alpha3, alpha5, alpha7, alpha9, and alpha10. Studies on serum antibody production
      in M(1) and M(5) combined mAChR gene knockout (KO) mice immunized with ovalbumin
      (OVA) revealed that M(1)/M(5) mAChRs up-regulate TNF-alpha, IFN-gamma and IL-6
      production in spleen cells, leading to an elevation of serum anti-OVA specific
      IgG(1). In contrast, studies of nAChR alpha7 subunit gene KO mice immunized with
      OVA show that alpha7 nAChRs down-regulate these proinflammatory cytokines,
      thereby leading to a reduction of anti-OVA specific IgG(1). Taken together, these
      findings demonstrate that both mAChRs and nAChRs modulate production of
      cytokines, such as TNF-alpha, resulting in a modification of antibody production.
      These findings support the notion that a non-neuronal cholinergic system is
      involved in the regulation of immune cell function.

PMID- 22659390
TI  - Short-term effects of a smoking prevention website in American Indian youth.
AB  - BACKGROUND: The rate of smoking commercial tobacco products among American Indian
      youth is double the rate for white youth. Interventions are needed to reduce this
      disparity. OBJECTIVE: To test the feasibility of a Web-based intervention to
      influence attitudes toward and intentions about smoking cigarettes among American
      Indian youth who attended a Native summer camp in the Northern Plains. METHODS:
      The study website, the SmokingZine, was originally developed and tested in
      Canadian youth, then adapted to be appropriate for American Indian youth. We
      conducted a randomized controlled trial to test the influence of exposure to the
      adapted SmokingZine website on smoking attitudes and behaviors among American
      Indian youth 12-18 years of age. Participants assigned to the intervention group
      were given access to the website for 1 hour per day during their camp experience
      and asked to sign in to the site and use it. Control group participants were not
      given access to the site. RESULTS: A total of 52% of intervention youth signed in
      to the website at least once. Among nonsmokers, intentions to try a cigarette in
      the intervention group declined from 16% to 0%, and increased from 8% to 25% in
      the control group (P < .05). Compared with the control group, youth in the
      intervention group were more likely to help others quit (21 percentage point
      change in intervention versus no change in control; P < .05) and had less
      positive attitudes about the drug effects of smoking (-0.19 change in
      intervention versus 0.67 in control; P < .05). CONCLUSION: These data indicate
      that SmokingZine needs more long-term, rigorous investigation as a way to keep
      American Indian youth from becoming regular smokers. Because the intervention
      group could use computers only 1 hour per day, increasing access might result in
      more visits and a greater effect of the website on smoking behaviors.

PMID- 22659392
TI  - Neuropeptide FF and related peptides attenuates warm-, but not cold-water swim
      stress-induced analgesia in mice.
AB  - Neuropeptide FF (NPFF) belongs to a neuropeptide family including two receptors
      (NPFF(1) and NPFF(2)). NPFF system has been reported to play important roles in
      pain transmission. The aim of the present study was to investigate the roles of
      NPFF related peptides and their receptors in swim stress-induced analgesia (SIA).
      Nociceptive test was performed in mice stressed by forced swimming in water at 15
      degrees C (cold water swimming) or 32  degrees C (warm water swimming). Warm
      water swimming produced a naloxone-mediated antinociceptive effect. This warm
      water swim SIA was dose-dependently antagonized by i.c.v. injection of NPFF and
      two related peptides (3-30 nmol), NPVF and dNPA, which exhibited the highest
      selectivities for NPFF(1) and NPFF(2) receptors, respectively. Moreover, the
      selective NPFF receptor antagonist RF9 (30 nmol) was inactive by itself, but
      prevented the effects of NPFF and related peptides. Cold-water swimming produced
      a wilder analgesic effect that was blocked by MK-801, but not naloxone. However,
      NPFF system failed to modify the cold water swim stress-induced analgesia. These
      findings demonstrated that NPFF and related peptides attenuated opioid-mediated
      form of SIA via NPFF receptors in the brain, but not non-opioid swim stress
      induced analgesia. These data further support an anti-opioid character of NPFF
      system.

PMID- 22659393
TI  - Amygdala responsiveness to emotional words is modulated by subclinical anxiety
      and depression.
AB  - Several neuroimaging studies underlined the importance of the amygdala and
      prefrontal brain structures (e.g. dorsolateral prefrontal cortex [DLPFC]) for the
      processing of emotional stimuli and for emotion regulation. Many studies used
      visual scenes or faces as emotion-inducing material, and there is evidence that
      negative or positive words activate emotion-processing brain regions in the same
      way. However, no study so far focused on the influence of subclinical measures of
      anxiety or depression on the neural processing of emotional words. In this fMRI
      study, we therefore investigated brain activation to emotional words in relation
      to subclinical measures of trait anxiety and depression in a sample of 21 healthy
      subjects. We also assessed effects of subclinical anxiety and depression on
      amygdala-prefrontal coupling during negative (versus neutral) word reading. Both
      negative and positive words activated the amygdala, and negative-word processing
      revealed a positive correlation between amygdala activity and scores of trait
      anxiety and subclinical depression. During negative versus neutral word reading,
      subjects with high trait anxiety also showed a stronger functional coupling
      between left amygdala and left DLPFC. These results suggest a modulation of
      negative-word processing by subclinical depression and anxiety, as well as
      possible prefrontal compensatory processes during unintentional emotion
      regulation in subjects with higher trait anxiety.

PMID- 22659394
TI  - Rewarding and reinforcing effects of the NMDA receptor antagonist-benzodiazepine
      combination, Zoletil(r): difference between acute and repeated exposure.
AB  - Zoletil((r)) is a 1:1 combination of the N-methyl-d-aspartate (NMDA) receptor
      antagonist, tiletamine, and the benzodiazepine, zolazepam, commonly used as a
      veterinary anesthetic. There have been previous reports on the abuse of zoletil
      in humans, and these motivated us to investigate the rewarding and reinforcing
      effects of the drug. We experimented whether zoletil and its constituents,
      tiletamine and zolazepam, produces place preference and/or facilitates self
      administration. Then we compared the effects of zoletil to that of the
      recreationally abused veterinary anesthetic, ketamine. We also delved into the
      consequences of drug pre-exposure, thus parallel experiments were performed on
      rats pre-treated with the drug for 14 days. Our findings indicated that zoletil
      produced neither reward nor reinforcement in drug-naive rats; however, repeated
      pre-treatment of zoletil produced significant place preference and self
      administration. Tiletamine generated both place preference and self
      administration; while zolazepam induced place preference but was not self
      administered, even in pre-treated animals. The rewarding and reinforcing effects
      produced by zoletil were comparable to that of ketamine. Therefore, zoletil per
      se, has no motivational effects but the changes in neuronal functions and
      behavior consequential to repeated zoletil treatment may contribute in part to
      the addiction liability of the drug. Furthermore, the present study suggests that
      complex interactions occur with acute or repeated treatment of an NMDA receptor
      antagonist-benzodiazepine combination.

PMID- 22659395
TI  - Generalization of contextual fear depends on associative rather than non
      associative memory components.
AB  - Posttraumatic stress disorder (PTSD) is characterized by the presence of three
      major symptom clusters: persistent fear memories, hyperarousal, and avoidance.
      With a passage of time after the trauma, PTSD patients show an increase in
      unspecific fear and avoidance, a phenomenon termed "fear generalization". It is
      not clear whether fear generalization arises from the time-dependent growth of
      hyperarousal or changes in associative fear. The present study investigated
      behavioral and neuroanatomical correlates of non-associative and associative fear
      memory one week vs. one month after a trauma in a mouse model of PTSD with
      immediate vs. delayed foot shock application. The immediate shock procedure led
      to a lower contextual fear, but did not influence the hyperarousal (i.e.
      increased acoustic startle responses) assessed within the first week after the
      trauma. Only delayed shocked mice demonstrated generalization of contextual fear
      and an increase in generalized avoidance behavior, with no changes in
      hyperarousal one month after trauma. We observed the same increase in c-Fos
      expression following delayed and immediate shock presentation within the lateral,
      basolateral, central amygdala and CA1, CA3 and dentate gyrus of hippocampus,
      suggesting that all of these structures contribute to the development of
      hyperarousal. Only basolateral amygdala and dentate gyrus appeared to be
      additionally involved in encoding of contextual information. In summary, our
      results demonstrate the independence of associative and non-associative trauma
      related fear. They support the hypothesis that generalized fear emerges in
      consequence of forgetting specific stimulus attributes associated with the shock
      context.

PMID- 22659396
TI  - Social defeat interacts with Disc1 mutations in the mouse to affect behavior.
AB  - DISC1 (Disrupted-in-schizophrenia 1) is a strong candidate susceptibility gene
      for psychiatric disease that was originally discovered in a family with a
      chromosomal translocation severing this gene. Although the family members with
      the translocation had an identical genetic mutation, their clinical diagnosis and
      presentation varied significantly. Gene-environment interactions have been
      proposed as a mechanism underlying the complex heritability and variable
      phenotype of psychiatric disorders such as major depressive disorder and
      schizophrenia. We hypothesized that gene-environment interactions would affect
      behavior in a mutant Disc1 mouse model. We examined the effect of chronic social
      defeat (CSD) as an environmental stressor in two lines of mice carrying different
      Disc1 point mutations, on behaviors relevant to psychiatric illness: locomotion
      in a novel open field (OF), pre-pulse inhibition (PPI) of the acoustic startle
      response, latent inhibition (LI), elevated plus maze (EPM), forced swim test
      (FST), sucrose consumption (SC), and the social interaction task for sociability
      and social novelty (SSN). We found that Disc1-L100P +/- and wild-type mice have
      similar anxiety responses to CSD, while Q31L +/- mice had a very different
      response. We also found evidence of significant gene-environment interactions in
      the OF, EPM and SSN.

PMID- 22659397
TI  - Tianeptine treatment induces antidepressive-like effects and alters BDNF and
      energy metabolism in the brain of rats.
AB  - The present study was aimed at investigating the behavioral and molecular effects
      of tianeptine. To this aim, Wistar rats were treated with tianeptine (5, 10 and
      15 mg/kg) or imipramine (30 mg/kg) acutely and chronically. The results showed
      that both treatments reduced the immobility time. The BDNF levels were increased
      in the prefrontal cortex with tianeptine and decreased in the nucleus accumbens
      after acute treatment; in chronic treatment, BDNF levels were increased in the
      prefrontal and hippocampus with tianeptine. Acute treatment decreased the citrate
      synthase activity in the prefrontal cortex with tianeptine, and increased it in
      the amygdala with imipramine; chronic treatment increased the citrate synthase in
      the hippocampus with tianeptine. The creatine kinase was increased in the
      prefrontal cortex with tianeptine and in the amygdala with imipramine after acute
      treatment; chronic treatment increased the creatine kinase activity in the
      hippocampus with imipramine and tianeptine. The complex I activity was decreased
      in the prefrontal cortex with imipramine and increased in the hippocampus with
      tianeptine. The other complexes were increased with imipramine and tianeptine at
      all doses, but were related to the treatment given and the brain area studied.
      Chronic treatment increased the malate dehydrogenase activity in the amygdala
      with tianeptine. Acute treatment decreased the succinate activity in the
      prefrontal cortex, hippocampus and amygdala with tianeptine; chronic treatment
      increased the succinate activity in the hippocampus with tianeptine at all doses.
      In conclusion, tianeptine exerted antidepressant-like behavior which can be
      attributed to its effects on pathways related to depression, such as BDNF and
      metabolism energy.

PMID- 22659398
TI  - Evolutionary, genetic, environmental and hormonal-induced plasticity in the fate
      of organs arising from axillary meristems in Passiflora spp.
AB  - Tendrils can be found in different plant species. In legumes such as pea,
      tendrils are modified leaves produced by the vegetative meristem but in the grape
      vine, a same meristem is used to either form a tendril or an inflorescence.
      Passiflora species originated in ecosystems in which there is dense vegetation
      and competition for light. Thus climbing on other plants in order to reach
      regions with higher light using tendrils is an adaptive advantage. In Passiflora
      species, after a juvenile phase, every leaf has a subtending vegetative meristem,
      and a separate meristem that forms both flowers and a tendril. Thus, flowers are
      formed once a tendril is formed yet whether or not this flower will reach bloom
      depends on the environment. For example, in Passiflora edulis flowers do not
      develop under shaded conditions, so that tendrils are needed to bring the plant
      to positions were flowers can develop. This separate meristem generally forms a
      single tendril in different Passiflora species yet the number and position of
      flowers formed from the same meristem diverges among species. Here we display the
      variation among species as well as variation within a single species, P. edulis.
      We also show that the number of flowers within a specific genotype can be
      modulated by applying Cytokinins. Finally, this separate meristem is capable of
      transforming into a leaf-producing meristem under specific environmental
      conditions. Thus, behind what appears to be a species-specific rigid program
      regarding the fate of this meristem, our study helps to reveal a plasticity
      normally restrained by genetic, hormonal and environmental constraints.

PMID- 22659399
TI  - Improving the delineation of hydrocarbon-impacted soils and water through induced
      polarization (IP) tomographies: a field study at an industrial waste land.
AB  - Without a good estimation of samples representativeness, the delineation of the
      contaminated plume extent and the evaluation of volumes of hydrocarbon-impacted
      soils may remain difficult. To contribute to this question, a time domain induced
      polarization (IP) field experiment was conducted on an industrial waste land.
      Boreholes were drilled to specify the local geological context. Cross-hole
      seismic tomographies were performed to extend borehole logs and to draw an
      interpreted geological cross-section. Soil samples taken during drillings were
      analysed in laboratory. A preliminary survey was conducted to locate the IP
      profile. The polarization signatures linked to the presence of clayey sediments
      were filtered out from the data set. Chargeability and resistivity depth
      soundings were computed and compared to mean concentrations of total organic
      products to overcome the data support issue between the geophysical models and
      the spot samples of soils. A logarithmic relation between chargeabilities and
      smoothed hydrocarbon concentrations in soils was found. Taking into account
      contaminant's concentration thresholds defined in local codes and regulations
      allows defining chargeability classes to delineate hotspots on this site. This
      showed that IP tomography can be an accurate screening methodology. A statistical
      methodology is proposed to assess the efficiency of the investigation strategy.

PMID- 22659400
TI  - Inhibition of complex I regulates the mitochondrial permeability transition
      through a phosphate-sensitive inhibitory site masked by cyclophilin D.
AB  - Inhibition of the mitochondrial permeability transition pore (PTP) has proved to
      be an effective strategy for preventing oxidative stress-induced cell death, and
      the pore represents a viable cellular target for drugs. Here, we report that
      inhibition of complex I by rotenone is more effective at PTP inhibition than
      cyclosporin A in tissues that express low levels of the cyclosporin A
      mitochondrial target, cyclophilin D; and, conversely, that tissues in which
      rotenone does not affect the PTP are characterized by high levels of expression
      of cyclophilin D and sensitivity to cyclosporin A. Consistent with a regulatory
      role of complex I in the PTP-inhibiting effects of rotenone, the concentrations
      of the latter required for PTP inhibition precisely match those required to
      inhibit respiration; and a similar effect is seen with the antidiabetic drug
      metformin, which partially inhibits complex I. Remarkably (i) genetic ablation of
      cyclophilin D or its displacement with cyclosporin A restored PTP inhibition by
      rotenone in tissues that are otherwise resistant to its effects; and (ii)
      rotenone did not inhibit the PTP unless phosphate was present, in striking
      analogy with the phosphate requirement for the inhibitory effects of cyclosporin
      A [Basso et al. (2008) J. Biol. Chem. 283, 26307-26311]. These results indicate
      that inhibition of complex I by rotenone or metformin and displacement of
      cyclophilin D by cyclosporin A affect the PTP through a common mechanism; and
      that cells can modulate their PTP response to complex I inhibition by modifying
      the expression of cyclophilin D, a finding that has major implications for pore
      modulation in vivo.

PMID- 22659401
TI  - Spectroscopic studies of two spectral variants of light-harvesting complex 2
      (LH2) from the photosynthetic purple sulfur bacterium Allochromatium vinosum.
AB  - Two spectral forms of the peripheral light-harvesting complex (LH2) from the
      purple sulfur photosynthetic bacterium Allochromatium vinosum were purified and
      their photophysical properties characterized. The complexes contain
      bacteriochlorophyll a (BChl a) and multiple species of carotenoids. The
      composition of carotenoids depends on the light conditions applied during growth
      of the cultures. In addition, LH2 grown under high light has a noticeable split
      of the B800 absorption band. The influence of the change of carotenoid
      distribution as well as the spectral change of the excitonic absorption of the
      bacteriochlorophylls on the light-harvesting ability was studied using steady
      state absorption, fluorescence and femtosecond time-resolved absorption at 77K.
      The results demonstrate that the change of the distribution of the carotenoids
      when cells were grown at low light adapts the absorptive properties of the
      complex to the light conditions and maintains maximum photon-capture performance.
      In addition, an explanation for the origin of the enigmatic split of the B800
      absorption band is provided. This spectral splitting is also observed in LH2
      complexes from other photosynthetic sulfur purple bacterial species. According to
      results obtained from transient absorption spectroscopy, the B800 band split
      originates from two spectral forms of the associated BChl a monomeric molecules
      bound within the same complex.

PMID- 22659403
TI  - Determining pair distance distribution function from SAXS data using parametric
      functionals.
AB  - Small angle X-ray scattering (SAXS) experiments are widely applied in structural
      biology. The SAXS experiments yield one-dimensional profile that needs further
      analysis to reveal structural information. The pair distance distribution
      function (PDDF), P(r), can provide molecular structures more intuitively, and it
      can be used to guide ab initio model reconstructions, making it a critical step
      to derive P(r) from experimental SAXS profiles. To calculate the P(r) curves, a
      new method based on a specially designed parametric functional form is developed,
      and implemented in pregxs. This method is tested against both synthetic and
      experimental data, the estimated P(r) functions are in good agreement with
      correct or known P(r). The method can also predict the molecular size. In
      summary, the pregxs method is robust and accurate in P(r) determination from SAXS
      profiles. The pregxs source code and an online server are available at
      http://www.sastbx.als.lbl.gov.

PMID- 22659404
TI  - Mapping the road to recovery: the ClpB/Hsp104 molecular chaperone.
AB  - The AAA(+)-ATPases are a family of molecular motors which have been seconded into
      a plethora of cellular tasks. One subset, the Hsp100 molecular chaperones, are
      general protein remodellers that help to maintain the integrity of the cellular
      proteome by means of protein destruction or resurrection. In this review we focus
      on one family of Hsp100s, the homologous ClpB and Hsp104 molecular chaperones
      that convey thermotolerance by resolubilising and rescuing proteins from
      aggregates. We explore how the nucleotide binding and hydrolysis properties at
      the twelve nucleotide-binding domains of these hexameric rings are coupled to
      protein disaggregation, highlighting similarities and differences between ClpB
      and Hsp104.

PMID- 22659402
TI  - Mitochondrial DNA sequence variation is associated with free-living activity
      energy expenditure in the elderly.
AB  - The decline in activity energy expenditure underlies a range of age-associated
      pathological conditions, neuromuscular and neurological impairments, disability,
      and mortality. The majority (90%) of the energy needs of the human body are met
      by mitochondrial oxidative phosphorylation (OXPHOS). OXPHOS is dependent on the
      coordinated expression and interaction of genes encoded in the nuclear and
      mitochondrial genomes. We examined the role of mitochondrial genomic variation in
      free-living activity energy expenditure (AEE) and physical activity levels (PAL)
      by sequencing the entire (~16.5 kilobases) mtDNA from 138 Health, Aging, and Body
      Composition Study participants. Among the common mtDNA variants, the
      hypervariable region 2 m.185G>A variant was significantly associated with AEE
      (p=0.001) and PAL (p=0.0005) after adjustment for multiple comparisons. Several
      unique nonsynonymous variants were identified in the extremes of AEE with some
      occurring at highly conserved sites predicted to affect protein structure and
      function. Of interest is the p.T194M, CytB substitution in the lower extreme of
      AEE occurring at a residue in the Qi site of complex III. Among participants with
      low activity levels, the burden of singleton variants was 30% higher across the
      entire mtDNA and OXPHOS complex I when compared to those having moderate to high
      activity levels. A significant pooled variant association across the
      hypervariable 2 region was observed for AEE and PAL. These results suggest that
      mtDNA variation is associated with free-living AEE in older persons and may
      generate new hypotheses by which specific mtDNA complexes, genes, and variants
      may contribute to the maintenance of activity levels in late life.

PMID- 22659406
TI  - Antidepressant medications and osteoporosis.
AB  - Use of antidepressant medications that act on the serotonin system has been
      linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis.
      This article reviews current evidence for such effects, and identifies themes for
      future research. Serotonin receptors are found in all major types of bone cell
      (osteoblasts, osteocytes, and osteoclasts), indicating an important role of the
      neuroendocrine system in bone. Observational studies indicate a complex
      relationship between depression, antidepressants, and fracture. First, the
      presence of depression itself increases fracture risk, in relation with decreased
      BMD and an increase in falls. A range of aspects of depression may operate,
      including behavioral factors (e.g., smoking and nutrition), biological changes,
      and confounders (e.g., comorbidities and concomitant medications). A substantial
      proportion of depressed patients receive antidepressants, mostly selective
      serotonin reuptake inhibitors (SSRIs). Some of these have been linked to
      decreased BMD (SSRIs) and increased fracture risk (SSRIs and tricyclic agents).
      Current use of SSRIs and tricyclics increases fracture risk by as much as twofold
      versus nonusers, even after adjustment for potential confounders. While there is
      a dose-response relationship for SSRIs, the effect does not appear to be
      homogeneous across the whole class of drugs and may be linked to affinity for the
      serotonin transporter system. The increase in risk is the greatest in the early
      stages of treatment, with a dramatic increase after initiation, reaching a peak
      within 1 month for tricyclics and 8 months for SSRIs. Treatment-associated
      increased risk diminishes towards baseline in the year following discontinuation.
      The body of evidence suggests that SSRIs should be considered in the list of
      medications that are risk factors for osteoporotic fractures.

PMID- 22659405
TI  - Viruses in nondisinfected drinking water from municipal wells and community
      incidence of acute gastrointestinal illness.
AB  - BACKGROUND: Groundwater supplies for drinking water are frequently contaminated
      with low levels of human enteric virus genomes, yet evidence for waterborne
      disease transmission is lacking. OBJECTIVES: We related quantitative polymerase
      chain reaction (qPCR)-measured enteric viruses in the tap water of 14 Wisconsin
      communities supplied by nondisinfected groundwater to acute gastrointestinal
      illness (AGI) incidence. METHODS: AGI incidence was estimated from health diaries
      completed weekly by households within each study community during four 12-week
      periods. Water samples were collected monthly from five to eight households per
      community. Viruses were measured by qPCR, and infectivity assessed by cell
      culture. AGI incidence was related to virus measures using Poisson regression
      with random effects. RESULTS: Communities and time periods with the highest virus
      measures had correspondingly high AGI incidence. This association was
      particularly strong for norovirus genogroup I (NoV-GI) and between adult AGI and
      enteroviruses when echovirus serotypes predominated. At mean concentrations of 1
      and 0.8 genomic copies/L of NoV-GI and enteroviruses, respectively, the AGI
      incidence rate ratios (i.e., relative risk) increased by 30%. Adenoviruses were
      common, but tap-water concentrations were low and not positively associated with
      AGI. The estimated fraction of AGI attributable to tap-water-borne viruses was
      between 6% and 22%, depending on the virus exposure-AGI incidence model selected,
      and could have been as high as 63% among children < 5 years of age during the
      period when NoV-GI was abundant in drinking water. CONCLUSIONS: The majority of
      groundwater-source public water systems in the United States produce water
      without disinfection, and our findings suggest that populations served by such
      systems may be exposed to waterborne viruses and consequent health risks.

PMID- 22659407
TI  - Long-lasting efficacy of the cognitive enhancer cytotoxic necrotizing factor 1.
AB  - Rho GTPases are key regulators of the activity-dependent changes of neural
      circuits. Besides being involved in nervous system development and repair, this
      neural structural plasticity is believed to constitute the cellular basis of
      learning and memory. Here we report that concurrent modulation of cerebral Rho
      GTPases, including Rac, Rho and Cdc42 subfamilies, by Cytotoxic Necrotizing
      Factor 1 (CNF1, 10 fmol/kg intracerebroventricularly) improves object recognition
      in both C57BL/6J and CD1 mice. The improvement is long lasting, as it is still
      observed 90 days post treatment. At this time, the treatment is associated with
      enhancement of neurotransmission and long-term potentiation. The effects depend
      on changes in Rho GTPase status, since the recombinant molecule CNF1 C866S, in
      which the enzymatic activity was abolished through substitution of serine to
      cysteine at position 866, is ineffective. The study confirms the role of Rho
      GTPases in learning and suggests that a single administration of CNF1 is
      effective for a long time after administration. In general, the long-lasting
      cognition enhancing effect of CNF1 might be beneficial for the treatment of CNS
      disorders. This article is part of a Special Issue entitled 'Cognitive
      Enhancers'.

PMID- 22659408
TI  - Glycine release is regulated by metabotropic glutamate receptors sensitive to
      mGluR2/3 ligands and activated by N-acetylaspartylglutamate (NAAG).
AB  - The presence of metabotropic glutamate receptors (mGluRs) of group II modulating
      glycine exocytosis from glycinergic nerve endings of mouse spinal cord was
      investigated. Purified synaptosomes were selectively prelabeled with
      [(3)H]glycine through the neuronal transporter GlyT2 and subsequently depolarized
      by superfusion with 12 mM KCl. The selective mGluR2/3 agonist LY379268 inhibited
      the K(+)-evoked overflow of [(3)H]glycine in a concentration-dependent manner
      (EC(50) about 0.2 nM). The effect of LY379268 was prevented by the selective
      mGluR2/3 antagonist LY341495 (IC(50) about 1 nM). N-acetylaspartylglutamate
      (NAAG) inhibited [(3)H]glycine overflow with extraordinary potency (EC(50) about
      50 fmol). In contrast, glutamate was ineffective up to 0.1 nM, excluding that
      glutamate contamination of commercial NAAG samples is responsible for the
      reported activity of NAAG at mGluR3. LY341495 antagonized the NAAG inhibition of
      [(3)H]glycine release. The effect of a combination of maximally effective
      concentrations of LY379268 and NAAG exhibited no additivity. The non-hydrolysable
      NAAG analogue N-acetylaspartyl-beta-linked glutamate (beta-NAAG) antagonized NAAG
      and LY379268. In conclusion, our results show that glycinergic nerve endings in
      spinal cord are endowed with group II mGluRs mediating inhibition of glycine
      exocytosis. NAAG can activate these presynaptic receptors with extremely high
      affinity and with characteristics compatible with the reported mGluR3
      pharmacology. This article is part of a Special Issue entitled 'Metabotropic
      Glutamate Receptors'.

PMID- 22659410
TI  - New evidence for the involvement of prostaglandin receptor EP4b in ovulation of
      the medaka, Oryzias latipes.
AB  - A cDNA for a prostaglandin E(2) (PGE(2)) receptor subtype 4, EP4b (Ptger4b), was
      cloned from the medaka ovary. The effect of PGE(2) was examined using COS-7 cells
      expressing the recombinant Ptger4b protein. An increase in intracellular cAMP
      levels was observed when the cells were incubated with PGE(2), but the increase
      in cAMP levels was nullified by the addition of the EP4 antagonist GW627368X. The
      expression of ptger4b mRNA was drastically induced by the addition of pregnant
      mare serum gonadotropin to the in vitro culture of large preovulatory follicles.
      In in vitro ovulation studies of the effect of GW627368X addition on follicle
      ovulation, the critical timing of the PGE(2)/Ptger4b interaction was suggested to
      be between -1 and 0 h of ovulation. These results further substantiate that
      PGE(2)/Ptger4b signaling is involved in follicle rupture during ovulation in the
      medaka ovary.

PMID- 22659409
TI  - Attenuation of methamphetamine seeking by the mGluR2/3 agonist LY379268 in rats
      with histories of restricted and escalated self-administration.
AB  - Recent findings implicate group II metabotropic glutamate receptors (mGluR(2/3))
      in the reinforcing effects of psychostimulants and have identified these
      receptors as potential treatment targets for drug addiction. Here, we
      investigated the effects of mGluR(2/3) stimulation on cue- and drug-primed
      reinstatement in rats with different histories of methamphetamine (METH) self
      administration training, under two conditions: 16 daily sessions of short access
      (90 min/day, ShA), or 8 daily sessions of short access followed by 8 sessions of
      long access (6 h/day, LgA). Following self-administration and subsequent
      extinction training, rats were pretreated with the selective mGluR(2/3) agonist
      LY379268 (variable dose, 0-3 mg/kg), exposed to METH-paired cues or a priming
      injection of METH (1 mg/kg), and tested for reinstatement of METH-seeking
      behavior. LgA rats self-administered greater amounts of METH during the second
      half of training, but when pretreated with vehicle, ShA and LgA rats showed cue-
      and drug-primed reinstatement at equivalent response rates. However, LgA rats
      demonstrated greater sensitivity to mGluR(2/3) stimulation with attenuated
      responding during cue-induced reinstatement after 0.3 mg/kg and higher doses of
      LY379268, whereas ShA rats decreased cue-induced reinstatement behavior following
      1.0 mg/kg and 3.0 mg/kg LY379268. Additionally, both LgA and ShA rats exhibited
      decreased METH-primed reinstatement behavior following 0.3 mg/kg and higher doses
      of LY379268. A separate group of control rats was trained to self-administer
      sucrose pellets, and demonstrated attenuated cue-induced sucrose-seeking behavior
      following 1.0 and 3.0 mg/kg LY379268. Together, the results indicate that
      LY379268 has differential attenuating effects on cue-induced reinstatement
      behavior in rats with different histories of METH intake. This article is part of
      a Special Issue entitled 'Metabotropic Glutamate Receptors'.

PMID- 22659411
TI  - Stochastic modeling of Pseudomonas syringae growth in the phyllosphere.
AB  - Pseudomonas syringae is a gram-negative bacterium which lives on leaf surfaces.
      Its growth has been described using epifluorescence microscopy and image
      analysis; it was found to be growing in aggregates of a wide range of sizes. We
      develop a stochastic model to describe aggregate distribution and determine the
      mechanisms generating experimental observations. We found that a logistic birth
      death model with migration (time-homogeneous Markov process) provides the best
      description of the observed data. We discuss how to analyze the joint
      distribution of the numbers of aggregates of different sizes at a given time and
      explore how to account for new aggregates being created, that is, the joint
      distribution of the family size statistics conditional on the total number of
      aggregates. We compute the first two moments. Through simulations we examine how
      the model's parameters affect the aggregate size distribution and successfully
      explain the quantitative experimental data available. Aggregation formation is
      thought to be the first step towards pathogenic behavior of this bacterium;
      understanding aggregate size distribution would prove useful to understand the
      switch from epiphytic to pathogenic behavior.

PMID- 22659412
TI  - Novel cationic antimicrobial peptide GW-H1 induced caspase-dependent apoptosis of
      hepatocellular carcinoma cell lines.
AB  - Due to its malignancy, the development of effective therapeutic strategies for
      hepatocellular carcinoma (HCC) is of urgent needs. Natural antimicrobial peptides
      (AMPs), also known as host defense peptides (HDPs), not only act as direct
      antimicrobial agents, but also represent important regulators of the innate
      immune system. It has been reported that cationic AMPs may exhibit cancer
      selective toxicity. We have designed a series of novel AMPs with potent
      antimicrobial activity against a broad spectrum of bacterial pathogens. In the
      current study, we evaluate the antitumor potency of these AMPs toward HCC cell
      lines J5, Huh7, and Hep3B. Selected AMPs inhibit the viability of HCC cells in a
      dose-dependent fashion, while the normal 3T3 cells were significantly less
      susceptible to these AMPs. GW-H1 treatment (20MUM) of J5 cells for 24-72h
      resulted in the induction of apoptosis, as revealed by flow cytometry (increased
      sub-G1 populations), and western blot analysis for the appearance of activated
      caspase-3, -7 and -9 cleavages. Two-dimensional gel electrophoresis was applied
      to further analyze the AMP-responsive protein profiles of HCC, down-regulation of
      Hsp27, phophoglycerate kinase 1 and triosephosphate isomerase indicated that GW
      H1 may induce apoptosis, and further inhibit progression and metastasis of J5 HCC
      cells. FITC-labeled GW-H1 was found to attach to cell membrane initially, then
      translocated into the cytoplasm, and eventually membranous organelles or nucleus.
      GW-H1 induced a marked growth suppression of J5 xenografts in nude mice in a dose
      dependent manner. These findings provided support for future application of GW-H1
      as potential therapeutic agent for HCC.

PMID- 22659413
TI  - Biotic stress resistance in agriculture through antimicrobial peptides.
AB  - Antimicrobial peptides (AMPs) are the hosts' defense molecules against microbial
      pathogens and gaining extensive research attention worldwide. These have been
      reported to play vital role of host innate immunity in response to microbial
      challenges. AMPs can be used as a natural antibiotic as an alternative of their
      chemical counterpart for protection of plants/animals against diseases. There are
      a number of sources of AMPs including prokaryotic and eukaryotic organisms and
      are present, both in vertebrates and invertebrates. AMPs can be classified as
      cationic or anionic, based on net charges. Large number of databases and tools
      are available in the public domain which can be used for development of new
      genetically modified disease resistant varieties/breeds for agricultural
      production. The results of the biotechnological research as well as genetic
      engineering related to AMPs have shown high potential for reduction of economic
      losses of agricultural produce due to pathogens. In this article, an attempt has
      been made to introduce the role of AMPs in relation to plants and animals. Their
      functional and structural characteristics have been described in terms of its
      role in agriculture. Different sources of AMPs and importance of these sources
      has been reviewed in terms of its availability. This article also reviews the
      bioinformatics resources including different database tools and algorithms
      available in public domain. References of promising biotechnology research in
      relation to AMPs, prospects of AMPs for further development of genetically
      modified varieties/breeds are highlighted. AMPs are valuable resource for
      students, researchers, educators and medical and industrial personnel.

PMID- 22659414
TI  - A molecular dynamics investigation on the crizotinib resistance mechanism of
      C1156Y mutation in ALK.
AB  - Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that has recently
      been approved in the US for the treatment of non-small cell lung carcinoma
      (NSCLC). Despite its outstanding safety and efficacy, several resistant mutations
      against crizotinib have been detected in the treatment of NSCLC. However, in
      contrast to the widely accepted mechanism of steric hindrance by mutations at the
      active site, the mechanism by which the C1156Y non-active site mutation confers
      resistance against crizotinib remains unclear. In the present study, the
      resistance mechanism of C1156Y in ALK was investigated using molecular dynamics
      simulations. The results suggest that despite the non-active site mutation,
      C1156Y causes the dislocation of crizotinib as well as the indirect
      conformational changes in the binding cavity, which results in a marked decrease
      in the van der Waals and electrostatic interactions between crizotinib and ALK.
      The obtained results provide a detailed explanation of the resistance caused by
      C1156Y and may give a vital clue for the design of drugs to combat crizotinib
      resistance.

PMID- 22659415
TI  - GH-independent IGF-I action is essential to prevent the development of
      nonalcoholic steatohepatitis in a GH-deficient rat model.
AB  - The progression to nonalcoholic steatohepatitis (NASH) from simple steatosis is
      associated with the mitochondrial dysfunction, enhanced oxidative stress, and
      inflammation. Recently, it has been reported that the prevalence of NAFLD
      (nonalcoholic fatty liver disease)/NASH is increased in patients with adult
      growth hormone deficiency (AGHD), suggesting that the deficiencies in GH and
      insulin-like growth factor (IGF-I) are involved in the development of NAFLD/NASH;
      however, the precise underlying mechanism remains to be elucidated. To clarify
      the mechanisms and the specific contribution of GH and IGF-I in these conditions,
      we examined the liver of a GH-deficient rat model, spontaneous dwarf rat (SDR)
      and the effect of GH and IGF-I administration. SDR showed steatosis and fibrosis
      in the liver in line with the phenotype observed in AGHD. Serum AST and ALT
      levels and triglyceride content in the liver were significantly increased in the
      SDR compared with the control. Intriguingly, the mitochondrial morphology in the
      SDR hepatocyte was impaired and the area was significantly decreased.
      Furthermore, oxidative stress in the SDR liver was enhanced. These changes were
      improved not only by GH but also by IGF-I administration, suggesting that GH
      independent IGF-I action plays an essential role in the liver. In conclusion, we
      demonstrated that GH-deficient rat exhibits NASH and IGF-I plays an essential
      role to prevent the development of NASH. The improved mitochondrial function and
      reduced oxidative stress may contribute the effect of IGF-I in the liver.

PMID- 22659416
TI  - A conserved polylysine motif in CD86 cytoplasmic tail is necessary for
      cytoskeletal association and effective co-stimulation.
AB  - T cell activation requires both antigen specific and co-stimulatory signals that
      include the interaction of CD28 with its ligands CD80 and CD86. These signals are
      delivered by antigen presenting cells (APC) in the context of the immunological
      synapse (IS). Reorganization of the cytoskeleton is required for the formation
      and maintenance of the IS. Our results show that a highly conserved polylysine
      motif in CD86 cytoplasmic tail, herein referred to as the K4 motif, is
      responsible for the constitutive association of CD86 to the cytoskeleton in
      primary human APC as well as in a murine APC model. This motif is not involved in
      initial APC:T cell conjugate formation but mutation of the K4 motif affects CD86
      reorientation at the IS. Importantly, APCs expressing CD86 with mutated K4 motif
      are severely compromised in their capacity to trigger complete T cell activation
      upon peptide presentation as measured by IL-2 secretion. Altogether, our results
      reveal the critical importance of the cytoskeleton-dependent CD86 polarization to
      the IS and more specifically the K4 motif for effective co-signaling.

PMID- 22659417
TI  - Epstein-Barr Virus latent membrane protein 1 overcomes all-trans retinoic acid
      induced apoptosis by inhibiting retinoic acid receptor-beta2 expression.
AB  - Nasopharyngeal carcinoma is closely associated with infection with Epstein-Barr
      Virus (EBV); however, the mechanism is still unclear. Here, we report that the
      EBV oncoprotein, latent membrane protein 1 (LMP1), suppresses apoptotic cell
      death provoked by all-trans retinoic acid (ATRA) in NPC cells. For this purpose,
      LMP1 downregulated levels of Bak whilst it upregulated levels of Bcl2, lowering
      the ratio of Bak to Bcl2. In addition, LMP1 suppressed ATRA-mediated activation
      of Caspase 9, Caspase 3, and PARP but not Caspase 8 in Ad-AH cells, suggesting
      that LMP1 acts by blocking the activation of intrinsic apoptosis pathway by ATRA.
      These effects were almost completely abolished when levels of retinoic acid
      receptor-beta(2) (RAR-beta(2)) in the LMP1-expressing cells were recovered by
      either exogenous gene expression or treatment with a universal DNMT inhibitor, 5
      Aza-2'dC, indicating that LMP1 executes its antiapoptotic effects by
      downregulating levels of RAR-beta(2) via DNA methylation.

PMID- 22659418
TI  - A novel biosensor regulated by the rotator of F0F1-ATPase to detect
      deoxynivalenol rapidly.
AB  - A novel biosensor (immuno-rotary biosensor) was developed by conjugating
      deoxynivalenol (DON) monoclonal antibodies with the "rotator" epsilon-subunit of
      F(0)F(1)-ATPase within chromatophores with an epsilon-subunit monoclonal antibody
      biotin-avidin-biotin linker to capture DON residues. The conjugation conditions
      were then optimized. The capture of DON was based on the antibody-antigen
      reaction and it is indicated by the change in ATP synthetic activity of F(0)F(1)
      ATPase, which is measured via chemiluminescence using the luciferin-luciferase
      system with a computerized microplate luminometer analyzer. 10(-7)mg/ml of DON
      can be detected. The whole detection process requires only about 20min. This
      method has promising applications in the detection of small molecular compounds
      because of its rapidity, simplicity, and sensitivity.

PMID- 22659419
TI  - Beta-glucosidase 1 (GBA1) is a second bile acid beta-glucosidase in addition to
      beta-glucosidase 2 (GBA2). Study in beta-glucosidase deficient mice and humans.
AB  - Beta-glucosidase 1 (GBA1; lysosomal glucocerebrosidase) and beta-glucosidase 2
      (GBA2, non-lysosomal glucocerebrosidase) both have glucosylceramide as a main
      natural substrate. The enzyme-deficient conditions with glucosylceramide
      accumulation are Gaucher disease (GBA-/- in humans), modelled by the Gba-/-
      mouse, and the syndrome with male infertility in the Gba2-/- mouse, respectively.
      Before the leading role of glucosylceramide was recognised for both deficient
      conditions, bile acid-3-O-beta-glucoside (BG), another natural substrate, was
      viewed as the main substrate of GBA2. Given that GBA2 hydrolyses both BG and
      glucosylceramide, it was asked whether vice versa GBA1 hydrolyses both
      glucosylceramide and BG. Here we show that GBA1 also hydrolyses BG. We compared
      the residual BG hydrolysing activities in the GBA1-/-, Gba1-/- conditions (where
      GBA2 is the almost only active beta-glucosidase) and those in the Gba2-/-
      condition (GBA1 active), with wild-type activities, but we used also the GBA1
      inhibitor isofagomine. GBA1 and GBA2 activities had characteristic differences
      between the studied fibroblast, liver and brain samples. Independently, the
      hydrolysis of BG by pure recombinant GBA1 was shown. The fact that both GBA1 and
      GBA2 are glucocerebrosidases as well as bile acid beta-glucosidases raises the
      question, why lysosomal accumulation of glucosylceramide in GBA1 deficiency, and
      extra-lysosomal accumulation in GBA2 deficiency, are not associated with an
      accumulation of BG in either condition.

PMID- 22659421
TI  - A comparative analysis of the amounts and dynamics of transposable elements in
      natural populations of Drosophila melanogaster and Drosophila simulans.
AB  - Genes are important in defining genetic variability, but they do not constitute
      the largest component of genomes, which in most organisms contain large amounts
      of various repeated sequences including transposable elements (TEs), which have
      been shown to account for most of the genome size. TEs contribute to genetic
      diversity by their mutational potential as a result of their ability to insert
      into genes or gene regulator regions, to promote chromosomal rearrangements, and
      to interfere with gene networks. Also, TEs may be activated by environmental
      stresses (such as temperature or radiation) that interfere with epigenetic
      regulation systems, and makes them powerful mutation agents in nature. To
      understand the relationship between genotype and phenotype, we need to analyze
      the portions of the genome corresponding to TEs in great detail, and to decipher
      their relationships with the genes. For this purpose, we carried out comparative
      analyses of various natural populations of the closely-related species Drosophila
      melanogaster and Drosophila simulans, which differ with regard to their TE
      amounts as well as their ecology and population size.

PMID- 22659422
TI  - [Progress of research on 5-hydroxymethylcytosine].
AB  - 5-methylcytosine (5mC) in cytosine-guanine dinucleotide (CpG) is a usual
      epigenetic modification in mammals. It plays crucial roles in gene regulation,
      development, genomic imprinting and so on. In the last three years, it was
      discovered that in addition to 5mC, another modified cytosine base-5
      hydroxymethylcytosine (5hmC) was abundant in many mammalian tissues, which may
      have different biological function from 5mC. This paper reviews the recent
      progresses in the studies of 5hmC.

PMID- 22659423
TI  - [Chromosomal and genomic aberrations in esophageal squamous cell carcinoma].
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies
      with poor prognosis in China. Patients with ESCC may present with vague symptoms
      in early stage and most of the cases are diagnosed at advanced stage, without the
      chance of optimal therapy. In the development and progression of ESCC,
      cytogenetic and molecular aberrations are frequently observed. This review is to
      summarize the advances in the chromosomal and genomic alterations of ESCC
      reported recently.

PMID- 22659420
TI  - Toxoplasma ISP4 is a central IMC sub-compartment protein whose localization
      depends on palmitoylation but not myristoylation.
AB  - Apicomplexan parasites utilize a peripheral membrane system called the inner
      membrane complex (IMC) to facilitate host cell invasion and parasite replication.
      We recently identified a novel family of Toxoplasma IMC Sub-compartment Proteins
      (ISP1/2/3) that localize to sub-domains of the IMC using a targeting mechanism
      that is dependent on coordinated myristoylation and palmitoylation of a series of
      residues in the N-terminus of the protein. While the precise functions of the
      ISPs are unknown, deletion of ISP2 results in replication defects, suggesting
      that this family of proteins plays a role in daughter cell formation. Here we
      have characterized a fourth ISP family member (ISP4) and discovered that this
      protein localizes to the central IMC sub-compartment, similar to ISP2. Like
      ISP1/3, ISP4 is dispensable for the tachyzoite lytic cycle as the disruption of
      ISP4 does not produce any gross replication or growth defects. Surprisingly,
      targeting of ISP4 to the IMC membranes is dependent on residues predicted for
      palmitoylation but not myristoylation, setting its trafficking apart from the
      other ISP proteins and demonstrating distinct mechanisms of protein localization
      to the IMC membranes, even within a family of highly related proteins.

PMID- 22659424
TI  - [Research progress on influenza antiviral small RNAs].
AB  - Worldwide influenza caused by influenza virus is a respiratory disease which
      threats the public health by seasonal epidemics or global influenza outbreak.
      Vaccines and drugs are current therapies, but there are many restricted factors
      such as neurotoxicity, side effects of gastrointestinal, and drug resistance. New
      technologies, particularly RNAi mediated by small RNAs, has become a potential
      and robust method in influenza antiviral research for its high efficiency,
      specific, and speedy. Following the spread and epidemic of the influenza virus,
      application of small RNAs into influenza antiviral research has been reported
      increasingly. The small RNAs, PA-2087, NP-1496, and M-950, which targets PA, NP,
      and M2 genes, respectively, are the most effective anti-influenza siRNAs up to
      now. siRNA of targeting conservative region of different influenza viral genes
      has broader effect on virus inhibition. The combination of siRNAs of targeting
      different genes can achieve better virus inhibition. In this review, we mainly
      described the progress of siRNAs and miRNAs for anti-influenza virus, and the
      prospects and hurdles of influenza RNAi therapy as well.

PMID- 22659425
TI  - [Research advance of dosage compensation and MSL complex].
AB  - Dosage compensation effect, which exists widely in eukaryotes with sexual
      reproduction, is an essential biological process that equalizes the level of gene
      expression between genders based on sex determination. In Drosophila, the male
      specific lethal (MSL) complex mediates dosage compensation by acetylating histone
      H4 lysine K16 on nucleosome of some specific sites on the male X chromosome,
      globally upregulates twofold expression of active X-linked genes from the single
      X chromosome, and makes up for the shortage that the male has only one single X
      chromosome in male Drosophila. Up to date, the structure of basic components of
      MSL complex, which consists of at least five protein subunits and two non-coding
      RNAs, has already been revealed, and the interaction sites among these components
      have also been generally identified. Furthermore, abundant researches on
      recognition mechanism of the complex have been published. In contrast, many
      studies have revealed that mammalian dosage compensation functions by silencing
      gene expression from one of the two X chromosomes in females. The main components
      of mammalian MSL complex have already been identified, but the knowledge of their
      function is limited. Up to now, research of MSLs in teleosts is scarcely studied.
      This review summarizes the similarities and differences among dosage compensation
      mechanisms of nematodes, fruit flies and mammals, introduces the recent research
      advances in MSL complex, as well as molecular mechanism of dosage compensation in
      fruit fly, and finally addresses some problems to be resolved. Meanwhile, the
      diversity of msl3 gene in fishes is found by synteny analysis. This information
      might provide insightful directions for future research on the mechanisms of
      dosage compensation in various species.

PMID- 22659426
TI  - [Advances on genome-wide association study for economically important traits in
      dairy cattle].
AB  - Milk performance traits have been considered as the most important production
      traits. With the development of balance breeding sense, much attention has been
      paid to the functional traits such as reproduction, type, health, and longevity
      traits, which is put into breeding programs. Identification of major genes or
      genetic markers for milk production and functional traits and their applications
      in breeding programs of dairy cattle are expected to improve the genetic progress
      of these traits. Occurrence of millions of SNPs in whole genome and high
      throughout genotyping techniques has made genome-wide association study to be an
      important strategy to identify genes responsible for economic traits in domestic
      animals. This paper reviewed the advances on genome-wide association study for
      milk production traits and functional traits in dairy cattle.

PMID- 22659427
TI  - [Biological function of the Somatic embryogenesis receptor-like kinases in
      plant].
AB  - Somatic Embryogenesis Receptor-Like Kinases (SERKs) belong to the LRR-RLK II
      subfamily, which contain three conserved domains: an extracellular domain, a
      transmembrane domain, and an intracellular catalytic kinase domain. Previous
      studies had found that SERKs play many roles during plant development. This
      review made a brief introduction about the character of the SERKs and described
      the biological function of these proteins in somatic embryogenesis, sporogenesis,
      hormone response and host defense response. The research value and the
      application prospects of the SERKs were discussed.

PMID- 22659428
TI  - [ABA signaling mediated by PYR/PYL/RCAR in plants].
AB  - Abscisic acid (ABA) is a phytohormone that plays critical roles in numerous
      developmental stages as well as in adaptive responses to biotic and abiotic
      stresses. Recent breakthroughs in the field of ABA signaling have indicated that
      there are three major components, PYR/PYL/RCAR (an ABA receptor), type 2C protein
      phosphates (PP2C, a negative regulator), and SNF1-related protein kinase 2
      (SnRK2, a positive regulator). Further results show that these three proteins
      construct a double negative regulatory system, PYR/PYL/RCAR-| PP2C-| SnRK2, to
      regulate ABA signal responses in plant cells. Moreover, the combination patterns
      of these components in vivo are restricted by spatio-temporal and biochemical
      determinants and the combinational variation in the ABA signalosome is specific
      to different ABA signal responses. This review summarizes recent advances of
      study on the molecular basis and regulatory mechanism of PYR/PYL/RCAR-mediated
      ABA signaling pathway and PYR/PYL/RCAR-PP2C-SnRK2 complex-mediated ABA signal
      regulation network in plants. The perspectives related to this study are
      proposed.

PMID- 22659429
TI  - [Caloric restriction suppresses endothelial cells senescence via down-regulation
      of NOX4 induced by HNF3gamma].
AB  - The aim of current study is to investigate the molecular mechanism that  caloric
      restriction (CR) suppresses endothelial cells senescence. Human aortic
      endothelial cells (HAECs) were divided into 5 groups: control group, high caloric
      group (about 1.5 times caloric intake of control group), low caloric group (about
      0.5 times caloric intake of control group), siRNA plus low caloric group (low
      caloric treatment pretreated with special siRNA targeting hepatocyte nuclear
      factor 3gamma (HNF3gamma)), and siRNA plus high caloric group (high caloric
      treatment pretreated with special siRNA targeting HNF3gamma). The gene and
      protein expressions of HNF3gamma and NADPH oxidase 4 (NOX4) were quantified by
      real-time quantitative PCR (RT-qPCR) and Western blotting, respectively.
      Intracellular reactive oxygen species (ROS) production was measured by flow
      cytometry. Endothelial cells senescence was assayed by senescence associated beta
      galactosidase staining. After verifying the binding of HNF3gamma to NOX4 promoter
      region by chromatin immunoprecipitation assay (ChIP), NOX4 promoter activity was
      assayed by dual-luciferase reporter system. Compared with the control group, the
      mRNA and protein expression levels of HNF3gamma,and the ratio of phosphorylated 
      HNF3gamma protein increased significantly (P<0.05) in low caloric group, and
      decreased significantly (P<0.05) in high caloric group and siRNA plus low or high
      caloric group; whereas the mRNA and protein levels of NOX4 intracellular ROS and
      endothelial cells senescence decreased significantly (P<0.05) in low caloric
      group and increased significantly (P<0.05) in high caloric group and siRNA plus
      low or high caloric group. ChIP result showed there were four HNF3gamma binding
      sites in NOX4 gene promoter region (-6, -76, -249 and -954 bp) and HNF3gamma
      could bind to all 4 predicted sites. According to the results of dual-luciferase
      reporter system, HNF3gamma binding to 1 site (-6 bp), 2 sites (-6 and -76 bp), 3
      sites (-6, -76 and -249 bp) and 4 sites(-6, -76, -249 and -954 bp) could suppress
      NOX4 promoter activity to 80.15+/-4.64%, 40.02.+/-2.15%, 16.46+/-2.24% and
      12.13+/-1.46% compared with that of baseline, respectively ( P<0.05). In a word,
      low caloric intake decreases the production of intracellular ROS and suppresses
      endothelial cells senescence through promoting HNF3gamma binging to NOX4 promoter
      region and inhibiting NOX4 gene expression induced by up-regulated HNF3gamma.

PMID- 22659430
TI  - [Impact of maternal genetic effect on genetic parameter estimation of production
      traits for Qinghai fine-wool sheep].
AB  - The maternal genetic effects on estimating genetic parameters for growth traits
      and wool traits of Qinghai fine-wool sheep were investigated.The genetic
      parameters for production traits of Qinghai fine-wool sheep were estimated by
      average information restricted maximum likelihood (AIREML) with different animal
      models, and the differences between different animal models were tested by
      likelihood ratio test. Fixed effects, direct genetic effects, and residual
      effects were included all models; and random effects were individual permanence
      environmental effects, maternal genetic effects, and maternal permanence
      environmental effects. The six models differ in the way of considering random
      effects: in model 1 individual permanence environmental effects, maternal genetic
      effects, and maternal permanence environmental effects were not contained; in
      model 2 maternal permanence environmental effects were included; in model 3
      maternal genetic effects were included; in model 4 both maternal genetic effects
      and maternal permanence environmental effects were include; in model 5 both
      individual permanence environmental effects and maternal genetic effects were
      contained;in model 6 all random effects were contained. The direct heritabilities
      were 0.1896~0.3781, 0.2537~0.2890, 0.2244~0.3225, 0.2205~0.3983, 0.1218~0.1490,
      0.0983~0.4802, and 0.1170~0.1311 for birth weight, weaning weight, yearling
      weight, hogget weight,greasy fleece weight, fiber diameter, and staple
      length,respectively. Compared with model 1, model 3 was-significant(P<0.01) for
      birth weight and weaning weight, other models were not significant (P>0.05)for
      Yearling weight, Hogget weight; and paralleled with model 6, both model 4 and
      model 5 were significant(P<0.01) for fiber diameter,model 4 was
      significant(P<0.05) for staple length, and other models were not
      significant(P>0.05) for greasy fleece weight by likelihood ratio test.The
      maternal effects were important determinants of estimated the genetic parameters
      for birth weight, weaning weigh, fiber diameter, and staple length, but were not
      significant for yearling weight, and hogget weight, and was slightly significant
      for greasy fleece weight.

PMID- 22659431
TI  - [Factors analysis and genetic parameter estimation of female reproductive traits
      in pigs].
AB  - Reproductive performance of stock sows is one of the important factors of
      economic impact in pig farms. In this study, 8491 litter records from 2699 sows
      of Yorkshire, Landrace, and Duroc were analyzed using fixed model to determine
      the effect of parity, mating season, and breed on total number born (TNB), number
      healthy birth (NHB), litter birth weight (LWB), number weak birth (NWB),
      stillbirth, mummy fetus, and deform fetus by the least square analysis. Genetic
      parameters of the above traits were estimated by restricted maximum likelihood
      (REML) procedure. In addition, the effectiveness of pure-breeding and cross
      breeding on litter performance were compared. The results showed that, parity,
      mating season, and breed had significant effect on TNB, NHB, and LWB(P <
      0.001).The effects of parity and breed were significant on NWB(P < 0.001), while
      mating season had non-significant effect on NWB. Parity showed significant effect
      on stillbirth, while the effect of mating season and breed was not significant.
      Parity, mating season, and breed had no significant effect on mummy fetus and
      deform fetus. Landrace?*Large White? showed the best litter performance,
      including TNB, NHB, and LWB. Moreover, LWB of Landrace depicted the highest
      heritability, while other traits were all bellow 0.2. The genetic correlation
      between TNB and NHB, NHB and LWB were higher than 0.96 in the three breeds. These
      results provided reference data for minimizing low-reproductive performance
      caused by non-infectious factors and improving sow reproductive performance in
      pig farms.

PMID- 22659432
TI  - [Phylogenetic relationships among Orthoptera insect groups based on complete
      sequences of 16S ribosomal RNA].
AB  - In order to reconstruct a robust phylogenetic relationship among major groups of
      Orthoptera and to explore the phylogenetic utility and performance of 16S
      Ribosomal RNA gene, complete sequences of 16S Ribosomal RNA were sequenced from
      18 species in 9 families and 4 superfamilies of Orthoptera, and analyzed with
      other 40 species that have been completely sequenced. The result showed that the
      average length of 16S Ribosomal RNA was 1 310 bp. The positions of Tridactuloidea
      and Gryllotalpidae in Orthoptera were uncertain based on the 16S rRNA data, and
      the phylogenetic relationships of other major groups in Orthoptera were rather
      robust. Except for Oedipodidae and Gomphoceridae, Acrididae, Catantopidae, and
      Arcypteridae in Xia's taxonomic system were not monophyletic groups, and the
      genetic distances among the five groups were small. This indicates that the five
      families should be combined into one family. The genetic distances among
      Pamphagidae, Chrotogonidae, and Pyrgomorphidae were also small. The loops of 16S
      rRNA gene could provide more information than stems when they were used for
      phylogenetic analysis. Complete sequence of 16S rRNA gene can be used to
      reconstruct robust phylogenetic relationship at the taxonomic category of
      species, genera, and suborder in Orthoptera, but lack of resolution at family and
      superfamily levels.

PMID- 22659433
TI  - [Expression and enzyme activity analysis of Djtry in planarian Dugesia japonica].
AB  - The cDNA Djtry, encoding a planarian trypsin, was identified from the cDNA
      library of Dugesia japonica. Multiple alignment analysis showed that the
      Tryps_SPc domain contained the incompletely conserved catalytic triad in which
      the first amino acid His was substituted by Lys. Phylogenetic analysis indicateed
      that Djtry protein falls at the base of other animal trypsins. The Djtry cDNA was
      cloned into a bacterial vector pET-28a and was transferred into E. coli BL21. The
      His-tagged Djtry fusion protein expression was induced by IPTG. SDS-PAGE analysis
      revealed that the Djtry was expressed as inclusion bodies in E. coli BL21 with
      the estimated molecular weight of approximately 26 kDa. Western blotting with His
      tag antibody showed that the antibody was reacted with the fusion protein after
      refolding. Compared to bovine trypsin using BAEE as special substrate of trypsin,
      the enzyme activity of Djtry was measured. These results indicate that Djtry
      represents the archetype of animal trypsins, and this type of mutational trypsin
      Djtry still performs the trypsin nature with slightly weaker activity.

PMID- 22659434
TI  - [Mapping of Sanming dominant genic male sterility gene in rice].
AB  - The mutant of "Sanming Dominant Genic Male Sterile Rice" was found from an F2
      population of cross "SE2lS/Basmati370" by Sanming Institute of Agricultural
      Science in 2001. It has proven that the male sterility of this mutant is
      controlled by a dominant gene (named as SMS). By multiple backcrosses, this
      dominant male sterile allele was introduced into the genetic background of an
      indica rice cultivar Jiafuzhan (which was known as Jiabuyu). In order to map SMS,
      a mapping population was constructed by crossing Jiabuyu with a japonica cultivar
      Nipponbare and further crossing the F1 with Jiafuzhan. By bulked segregant
      analysis and linkage analysis using SSR and INDEL markers, SMS was mapped to a 99
      kb interval between INDEL markers ZM30 and ZM9 on chromosome 8. This result will
      facilitate cloning of SMS.

PMID- 22659435
TI  - [Expression analysis of the Medicago truncatula floral specific expression
      genes].
AB  - The expression of genes specific to floral organ is important for the floral
      organ formation and development in Medicago truncatula. Screening of the genes
      specifically expressed in M. truncatula flowers and comparing the expression
      patterns of their orthologous homologous genes among different model plants can
      provide novel insights into the functions of these genes in controlling the
      floral organ development in M. truncatula. According to the expression profile
      data of PISTILLATA (PI), we screened 97 genes specifically expressed in M.
      truncatula floral organs (ratio>=10 and Z>=7.9). Their homolog genes were also
      identified in Arabidopsis thaliana, soybean (Glycine max L.), Lotus japonicus,
      and rice (Oryza sativa L.). The results of comparing the gene expression levels,
      the gene expression patterns, and the gene functions among these species
      indicated that the expression variation of the orthologous homolog genes was
      small in the kindred species and was great in distant species. Furthermore, we
      compared the cis-acting regulatory elements of the genes, which had large
      expression variation among different plants. These results suggest that the great
      discrepancy of the orthologous homolog gene expression caused by the different
      character of cis-element in the promoter region.

PMID- 22659436
TI  - [Bioinformatic research of the family of PEX11, peroxisome proliferous factor in
      fungus].
AB  - The family members of PEX11 are key factors involved in regulation of peroxisome
      proliferation. Sixty-six PEX11p candidates of PEX11 gene family from 26
      representative fungal species were obtained and analyzed by bioinformatic
      strategies. In most filamentous fungi, 2 or 3 potential PEX11ps were found, in
      contrast with 1 or 2 in yeast species. Compared with other fungal species, the
      Ascomycetes tend to have more PEX11ps, and even 5 in several individuals. The
      data of phylogenetic analysis and protein structure indicated that all of the
      PEX11ps were divided into 3 groups: I, II, and III. The members of group I and
      group III existed in most species, while those in group II were found only in
      Pezizomycotina. By MEME analysis, 5-6 conserved motifs were found in each
      PEX11ps. Among them,motif 8 in C-terminal had the most conservation, indicating
      that this motif probably plays a key role in maintaining the proper function of
      PEX11p.

PMID- 22659437
TI  - [Application of case-based method in genetics and eugenics teaching].
AB  - Genetics and Eugenics is a cross-discipline between genetics and eugenics. It is
      a common curriculum in many Chinese universities. In order to increase the
      learning interest, we introduced case teaching method and got a better teaching
      effect. Based on our teaching practices, we summarized some experiences about
      this subject. In this article, the main problem of case-based method applied in
      Genetics and Eugenics teaching was discussed.

PMID- 22659438
TI  - Targeting Toll-like receptors by chloroquine protects mice from experimental
      cerebral malaria.
AB  - Excessive production of proinflammatory cytokines, elicited mostly by Th1 cells,
      is an important cause of cerebral malaria (CM). Dendritic cells (DCs), a critical
      link between innate and adaptive immune responses, rely heavily on Toll-like
      receptor (TLR) signaling. Using C57BL/6 mice infected with Plasmodium berghei
      ANKA (PbA) as an experimental CM model, we first confirmed that inhibition of
      TLR9 by suppressive oligodeoxynucleotides protected mice from CM. In addition to
      being a well-known antimalarial, chloroquine (CQ) has been used as an
      immunomodulator of endocytic TLRs because it inhibits endosomal acidification. We
      found that immediately before and shortly after infection by PbA, treatment with
      a single dose of 50 mg/kg of CQ protected mice from experimental CM. Both CQ
      treatments significantly inhibited expression of TLR9 and MHC-II on DCs, and
      reduced the number of myeloid and plasmatocytoid DCs at 3 and 5 days after
      infection. Consequently, activation of CD4+ T cells, especially the expansion of
      the Th1 subsets, was dramatically inhibited in CQ treated groups, which was
      accompanied by a remarkable decline in the production of Th1 type proinflammatory
      mediators IFN-gamma, TNF-alpha, and nitric oxide. Taken together, these results
      corroborated the involvement of TLR9 in CM pathogenesis and suggest that
      interference with the activation of this receptor is a promising strategy to
      prevent deleterious inflammatory response mediating pathogenesis and severity of
      malaria.

PMID- 22659439
TI  - The 3D structure and function of digestive cathepsin L-like proteinases of
      Tenebrio molitor larval midgut.
AB  - Cathepsin L-like proteinases (CAL) are major digestive proteinases in the beetle
      Tenebrio molitor. Procathepsin Ls 2 (pCAL2) and 3 (pCAL3) were expressed as
      recombinant proteins in Escherichia coli, purified and activated under acidic
      conditions. Immunoblot analyses of different T. molitor larval tissues
      demonstrated that a polyclonal antibody to pCAL3 recognized pCAL3 and cathepsin L
      3 (CAL3) only in the anterior two-thirds of midgut tissue and midgut luminal
      contents of T. molitor larvae. Furthermore, immunocytolocalization data indicated
      that pCAL3 occurs in secretory vesicles and microvilli in anterior midgut.
      Therefore CAL3, like cathepsin L 2 (CAL2), is a digestive enzyme secreted by T.
      molitor anterior midgut. CAL3 hydrolyses Z-FR-MCA and Z-RR-MCA (typical cathepsin
      substrates), whereas CAL2 hydrolyses only Z-FR-MCA. Active site mutants
      (pCAL2C25S and pCAL3C26S) were constructed by replacing the catalytic cysteine
      with serine to prevent autocatalytic processing. Recombinant pCAL2 and pCAL3
      mutants (pCAL2C25S and pCAL3C26S) were prepared, crystallized and their 3D
      structures determined at 1.85 and 2.1 A, respectively. While the overall
      structure of these enzymes is similar to other members of the papain superfamily,
      structural differences in the S2 subsite explain their substrate specificities.
      The data also supported models for CAL trafficking to lysosomes and to secretory
      vesicles to be discharged into midgut contents.

PMID- 22659440
TI  - Transcriptome comparison between honey bee queen- and worker-destined larvae.
AB  - Caste differentiation in the female honey bee is one of the most intriguing
      polyphenism phenomena. This developmental switch depends on the differential
      expression of entire suites of the genes involved in the larval fate between the
      queens and workers. In this study, we compared the transcriptome differences
      between full-sister queen- (QL) and worker-destined larvae (WL) using high
      throughput RNA-Seq. QL and WL at fourth (L4) and fifth instar (L5) were used to
      prepare four libraries and to generate 50,191,699 (QL4), 57,628,541 (WL4),
      56,613,619 (QL5), and 58,626,829 (WL5) usable reads, which were assembled into
      groups of 7,952, 7,993, 7,971, and 8,023 genes, respectively. The transcriptome
      changes were investigated using the DEGs Package (DEGseq), which resulted in more
      than 4,500 differentially expressed genes (DEGs) between the castes. Eight of the
      DEGs were verified by quantitative real-time RT-PCR (qRT-PCR), and the results
      supported our sequencing data. All of the DEGs were analysed using Web Gene
      Ontology Annotation Plot (WEGO) and then mapped using the Kyoto Encyclopedia of
      Genes and Genomes (KEGG) database. These results suggest that over 70% of the
      DEGs in each instar were more highly expressed in QL than in WL, possibly
      suggesting that the QL genes had higher transcriptional activity than the WL
      genes during differentiation. The same gene set is active (but differentially
      expressed) in both castes, which in turn result in dimorphic females. The L4
      stage is a very active gene expression period for both QL and WL before their
      pupal stage. The activity of the mTOR (a target of rapamycin) encoding gene in
      the mTOR signalling pathway is higher in QL4 than in WL4, and this difference was
      no longer present by the L5 feeding stage. The genes down-stream of mTOR
      maintained this change at the L5 stage. These results could contribute to an in
      depth study of the candidate genes during honey bee caste differentiation and
      improve our current understanding of the polyphenism phenomenon in insects.

PMID- 22659441
TI  - Identification, characterization and the interaction of Tollip and IRAK-1 in
      grass carp (Ctenopharyngodon idellus).
AB  - Tollip and IRAK-1 are key components of the TLR/IL-1R signaling pathway in
      mammals, which play crucial roles as mediators of the TLR/IL-1R signal
      transduction pathways. Although several TLRs have been found in fish, molecular
      associations, protein-protein interactions or the role of the TLR signaling
      pathway in infection-induced immunity in fish has received little attention. In
      this study, Tollip and IRAK-1 sequences of grass carp were isolated from a head
      kidney cDNA library. Full length transcripts and sequences of promoter regions
      were obtained by 3' and 5' RACE and genome walking, respectively. Reporter gene
      promoter constructs and real-time RT-PCR analysis was used to determine grass
      carp Tollip and IRAK-1 transcription pattern in tissues. Recombinant proteins
      were used for antibodies production. Phylogenetically, the grass carp loci
      clustered with previously reported Tollip and IRAK-1genes, respectively, and
      their sequences shared the highest identity with the genes of zebrafish (Danio
      rerio). The promoter region of grass carp Tollip and IRAK-1 proved to be active.
      After viral infection transcript levels of both loci were upregulated in most
      immune-related tissues in a time-dependent manner. Using antibodies produced in
      this study, immunofluorescence analysis indicated that Tollip and IRAK-1 were
      uniformly distributed and co-localized in the cytoplasm of CIK cells. After viral
      infection, however, Tollip and IRAK-1 both trended toward the cell membrane. Our
      results demonstrate the existence of Tollip and IRAK-1 proteins in teleost
      species, and suggest that Tollip-IRAK-1 complexes are being recruited to receptor
      complexes after stimulation with virus. These results provide novel insights into
      the role of the TLR signaling pathway in teleosts, especially the action of
      teleost Tollip and IRAK-1 and the interaction of these molecules as part of this
      pathway.

PMID- 22659442
TI  - Modulation of the IgM gene expression and IgM immunoreactive cell distribution by
      the nutritional background in gilthead sea bream (Sparus aurata) challenged with
      Enteromyxum leei (Myxozoa).
AB  - The aim of the present work was to determine if a plant protein-based diet
      containing vegetable oils (VO) as the major lipid source could alter the
      distribution of IgM immunoreactive cells (IRCs) and the IgM expression pattern in
      the intestine and haematopoietic tissues of gilthead sea bream (GSB) (Sparus
      aurata) challenged with the myxosporean Enteromyxum leei. In a first trial (T1),
      GSB fed for 9 months either a fish oil (FO) diet or a blend of VO at 66% of
      replacement (66VO diet) was challenged by exposure to parasite-contaminated water
      effluent. All fish were periodically and non-lethally sampled to know their
      infection status. After 102 days of exposure, samples of intestine and head
      kidney were obtained for IgM expression and immunohistochemical detection (IHC).
      Additional samples of spleen were taken for IHC. Fish were categorized as control
      (C, not exposed), and early (E), or late (L) infected. The 66VO diet had no
      effect on the number of IgM-IRCs in any of the tissues or on IgM expression in C
      fish, whereas the infection with E. leei had a strong effect on the intestine. A
      combined time-diet effect was also observed, since the highest expression and
      IRCs values were registered in the posterior intestine (Pi) of E-66VO fish. A
      positive correlation was found between IgM expression and the presence of IgM
      IRCs in the Pi. The effect of the time of infection was studied more in detail in
      a second trial (T2) in which samples of Pi were taken at 0, 24, 51, 91 and 133
      days after exposure to the parasite. A significant increase of the IgM expression
      was detected only in parasitized fish, and very late after exposure. These
      results show that the duration of the exposure to the parasite is the most
      determinant factor for the observed intestinal IgM increased phenotype which gets
      magnified by the feeding of a high VO-based diet.

PMID- 22659443
TI  - Spatiotemporal activity estimation for multivoxel pattern analysis with rapid
      event-related designs.
AB  - Despite growing interest in multi-voxel pattern analysis (MVPA) methods for fMRI,
      a major problem remains--that of generating estimates in rapid event-related (ER)
      designs, where the BOLD responses of temporally adjacent events will overlap.
      While this problem has been investigated for methods that reduce each event to a
      single parameter per voxel (Mumford et al., 2012), most of these methods make
      strong parametric assumptions about the shape of the hemodynamic response, and
      require exact knowledge of the temporal profile of the underlying neural
      activity. A second class of methods uses multiple parameters per event (per
      voxel) to capture temporal information more faithfully. In addition to enabling a
      more accurate estimate of ER responses, this allows for the extension of the
      standard classification paradigm into the temporal domain (e.g., Mourao-Miranda
      et al., 2007). However, existing methods in this class were developed for use
      with block and slow ER data, and there has not yet been an exploration of how to
      adapt such methods to data collected using rapid ER designs. Here, we demonstrate
      that the use of multiple parameters preserves or improves classification
      accuracy, while additionally providing information on the evolution of class
      discrimination. Additionally, we explore an alternative to the method of Mourao
      Miranda et al. tailored to use in rapid ER designs that yields equivalent
      classification accuracies, but is better at unmixing responses to temporally
      adjacent events. The current work paves the way for wider adoption of
      spatiotemporal classification analyses, and greater use of MVPA with rapid ER
      designs.

PMID- 22659445
TI  - A new approach for corticospinal tract reconstruction based on navigated
      transcranial stimulation and standardized fractional anisotropy values.
AB  - PURPOSE: To establish a novel approach for fiber tracking based on navigated
      transcranial magnetic stimulation (nTMS) mapping of the primary motor cortex and
      to propose a new algorithm for determination of an individualized fractional
      anisotropy value for reliable and objective fiber tracking. METHODS: 50 patients
      (22 females, 28 males, median age 58 years (20-80)) with brain tumors
      compromising the primary motor cortex and the corticospinal tract underwent
      preoperative MR imaging and nTMS mapping. Stimulation spots evoking muscle
      potentials (MEP) closest to the tumor were imported into the fiber tracking
      software and set as seed points for tractography. Next the individual FA
      threshold, i.e. the highest FA value leading to visualization of tracts at a
      predefined minimum fiber length of 110 mm, was determined. Fiber tracking was
      then performed at a fractional anisotropy value of 75% and 50% of the individual
      FA threshold. In addition, fiber tracking according to the conventional knowledge
      based approach was performed. Results of tractography of either method were
      presented to the surgeon for preoperative planning and integrated into the
      navigation system and its impact was rated using a questionnaire. RESULTS:
      Mapping of the motor cortex was successful in all patients. A fractional
      anisotropy threshold for corticospinal tract reconstruction could be obtained in
      every case. TMS-based results changed or modified surgical strategy in 23 of 50
      patients (46%), whereas knowledge-based results would have changed surgical
      strategy in 11 of 50 patients (22%). Tractography results facilitated
      intraoperative orientation and electrical stimulation in 28 of 50 (56%) patients.
      Tracking at 75% of the individual FA thresholds was considered most beneficial by
      the respective surgeons. CONCLUSIONS: Fiber tracking based on nTMS by the
      proposed standardized algorithm represents an objective visualization method
      based on functional data and provides a valuable instrument for preoperative
      planning and intraoperative orientation and monitoring.

PMID- 22659444
TI  - Investigating function and connectivity of morphometric findings--exemplified on
      cerebellar atrophy in spinocerebellar ataxia 17 (SCA17).
AB  - Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant
      neurodegenerative disorder characterized by progressive cerebellar ataxia but
      also a broad spectrum of other neuropsychiatric signs. As anatomical and
      structural studies have shown severe cerebellar atrophy in SCA17 and a
      differentiation of the human cerebellum into an anterior sensorimotor and
      posterior cognitive/emotional partition has been implicated, we aimed at
      investigating functional connectivity patterns of two cerebellar clusters of
      atrophy revealed by a morphometric analysis in SCA17 patients. In particular,
      voxel-based morphometry (VBM) revealed a large cluster of atrophy in SCA17 in the
      bilateral anterior cerebellum (lobule V) and another one in the left posterior
      cerebellum (lobules IX, VIIb, VIIIA, VIIIB). These two cerebellar clusters were
      used as seeds for functional connectivity analyses using task-based meta-analytic
      connectivity modeling (MACM) and task-free resting state connectivity analysis.
      Results demonstrated first consistent functional connectivity throughout the
      cerebellum itself; the anterior cerebellar seed showed stronger connectivity to
      lobules V, VI and to some extent I-IV, and the posterior cerebellar seed to the
      posterior lobules VI-IX. Importantly, the cerebellar anterior seed also showed
      consistently stronger functional connectivity than the posterior one with pre-
      and motor areas as well as the primary somatosensory cortex. In turn, task-based
      task-independent functional connectivity analyses revealed that the cerebellar
      posterior seed was linked with fronto-temporo-parietal areas as well as partly
      the insula and the thalamus, i.e., brain regions implicated in cognitive and
      affective processes. Functional characterization of experiments activating either
      cerebellar seed further corroborated this notion, revealing mainly motor-related
      functions for the anterior cluster and predominantly cognitive functions were
      associated for the posterior one. The differential functional connectivity of the
      cerebellar anterior and posterior cluster highlights the manifold connections and
      dichotomy of the human cerebellum, providing additional valuable information
      about probably disrupted cerebellar-cerebral connections and reflecting the brunt
      of motor but also the broad spectrum of neuropsychiatric deficits in SCA17.

PMID- 22659446
TI  - State of the art: Could nursing mothers be vaccinated with attenuated live virus
      vaccine?
AB  - Recently two cases of vaccine-associated neurologic disease have been reported in
      breastfed infants whose mothers had received live attenuated yellow fever
      vaccine. These two cases have focused attention on the transmission of attenuated
      yellow fever vaccine virus from mother to infant via breastfeeding, and more
      generally of all other live attenuated viruses used to immunize nursing mothers.
      This article provides an overview of the rare literature on possible virus
      excretion in breast milk after vaccination of nursing mothers with live
      attenuated virus vaccine and on cases of infection via breastfeeding in infants
      whose mothers had been vaccinated postpartum. Before implementing postpartum
      vaccination in a nursing mother, the vaccinator needs to weigh up the risk of
      transmission to and adverse effects in the baby from live vaccine virus against
      the beneficial effects of the vaccine for the mother, taking into account her
      need for vaccination.

PMID- 22659448
TI  - Phase III, randomized controlled trial to evaluate lot consistency of a trivalent
      subunit egg-based influenza vaccine in adults.
AB  - Vaccination is the most effective preventive strategy to control influenza. The
      demonstration of lot-to-lot consistency to confirm the reliability of the
      manufacturing process has become a mandatory step in vaccine development. This
      phase III, observer-blind, controlled trial assessed lot-to-lot consistency,
      immunogenicity, and safety of a subunit trivalent influenza vaccine (Agrippal(r),
      Novartis Vaccines and Diagnostics) in healthy adults aged 18-49 years. The
      immunogenicity and safety profile of Agrippal was compared with a control vaccine
      (Fluvirin(r), Novartis Vaccines and Diagnostics). A total of 1507 subjects were
      randomized 2:2:2:1 to receive one vaccination of one of the three lots of
      influenza vaccine or control vaccine. Antibody levels were measured by
      hemagglutination inhibition assay on days 1 and 22. Adverse reactions were
      solicited via diary cards for 7 days after vaccination, and unsolicited adverse
      events were collected throughout the study period. Equivalence of day 22 immune
      responses to the three lots was shown for each of the three strains. Robust
      immunogenic responses after one dose were observed for all vaccine groups, and
      both Center for Biologics Evaluation and Research criteria for licensure of
      influenza vaccines were met for all three virus strains. Both vaccines exhibited
      a robust safety profile and were well tolerated, with no differences in local and
      systemic solicited reactions or in unsolicited adverse events. The demonstration
      of consistency between manufacturing lots confirms for purposes of clinical
      development the reliability of the production process. The robust immunogenic
      responses and favorable safety profiles further support the use of trivalent
      subunit influenza vaccines Agrippal and Fluvirin for active immunization against
      influenza.

PMID- 22659449
TI  - A consultation on the optimization of controlled human malaria infection by
      mosquito bite for evaluation of candidate malaria vaccines.
AB  - Early clinical investigations of candidate malaria vaccines and antimalarial
      medications increasingly employ an established model of controlled human malaria
      infection (CHMI). Study results are used to guide further clinical development of
      vaccines and antimalarial medications as CHMI results to date are generally
      predictive of efficacy in malaria-endemic areas. The urgency to rapidly develop
      an efficacious malaria vaccine has increased demand for efficacy studies that
      include CHMI and the need for comparability of study results among the different
      centres conducting CHMI. An initial meeting with the goal to optimize and
      standardise CHMI procedures was held in 2009 with follow-up meetings in March and
      June 2010 to harmonise methods used at different centres. The end result is a
      standardised document for the design and conduct of CHMI and a second document
      for the microscopy methods used to determine the patency endpoint. These
      documents will facilitate high accuracy and comparability of CHMI studies and
      will be revised commensurate with advances in the field.

PMID- 22659447
TI  - Review of the United States universal varicella vaccination program: Herpes
      zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily
      on the Antelope Valley Varicella Active Surveillance Project data.
AB  - In a cooperative agreement starting January 1995, prior to the FDA's licensure of
      the varicella vaccine on March 17, the Centers for Disease Control and Prevention
      (CDC) funded the Los Angeles Department of Health Services' Antelope Valley
      Varicella Active Surveillance Project (AV-VASP). Since only varicella case
      reports were gathered, baseline incidence data for herpes zoster (HZ) or shingles
      was lacking. Varicella case reports decreased 72%, from 2834 in 1995 to 836 in
      2000 at which time approximately 50% of children under 10 years of age had been
      vaccinated. Starting in 2000, HZ surveillance was added to the project. By 2002,
      notable increases in HZ incidence rates were reported among both children and
      adults with a prior history of natural varicella. However, CDC authorities still
      claimed that no increase in HZ had occurred in any US surveillance site. The
      basic assumptions inherent to the varicella cost-benefit analysis ignored the
      significance of exogenous boosting caused by those shedding wild-type VZV. Also
      ignored was the morbidity associated with even rare serious events following
      varicella vaccination as well as the morbidity from increasing cases of HZ among
      adults. Vaccine efficacy declined below 80% in 2001. By 2006, because 20% of
      vaccinees were experiencing breakthrough varicella and vaccine-induced protection
      was waning, the CDC recommended a booster dose for children and, in 2007, a
      shingles vaccination was approved for adults aged 60 years and older. In the
      prelicensure era, 95% of adults experienced natural chickenpox (usually as
      children)-these cases were usually benign and resulted in long-term immunity.
      Varicella vaccination is less effective than the natural immunity that existed in
      prevaccine communities. Universal varicella vaccination has not proven to be cost
      effective as increased HZ morbidity has disproportionately offset cost savings
      associated with reductions in varicella disease. Universal varicella vaccination
      has failed to provide long-term protection from VZV disease.

PMID- 22659450
TI  - The oncogenic lung cancer fusion kinase CD74-ROS activates a novel invasiveness
      pathway through E-Syt1 phosphorylation.
AB  - Patients with lung cancer often present with metastatic disease and therefore
      have a very poor prognosis. The recent discovery of several novel ROS receptor
      tyrosine kinase molecular alterations in non-small cell lung cancer (NSCLC)
      presents a therapeutic opportunity for the development of new targeted treatment
      strategies. Here, we report that the NSCLC-derived fusion CD74-ROS, which
      accounts for 30% of all ROS fusion kinases in NSCLC, is an active and oncogenic
      tyrosine kinase. We found that CD74-ROS-expressing cells were highly invasive in
      vitro and metastatic in vivo. Pharmacologic inhibition of CD74-ROS kinase
      activity reversed its transforming capacity by attenuating downstream signaling
      networks. Using quantitative phosphoproteomics, we uncovered a mechanism by which
      CD74-ROS activates a novel pathway driving cell invasion. Expression of CD74-ROS
      resulted in the phosphorylation of the extended synaptotagmin-like protein E
      Syt1. Elimination of E-Syt1 expression drastically reduced invasiveness both in
      vitro and in vivo without modifying the oncogenic activity of CD74-ROS.
      Furthermore, expression of CD74-ROS in noninvasive NSCLC cell lines readily
      conferred invasive properties that paralleled the acquisition of E-Syt1
      phosphorylation. Taken together, our findings indicate that E-Syt1 is a mediator
      of cancer cell invasion and molecularly define ROS fusion kinases as therapeutic
      targets in the treatment of NSCLC.

PMID- 22659451
TI  - Molecular signature of smoking in human lung tissues.
AB  - Cigarette smoking is the leading risk factor for lung cancer. To identify genes
      deregulated by smoking and to distinguish gene expression changes that are
      reversible and persistent following smoking cessation, we carried out genome-wide
      gene expression profiling on nontumor lung tissue from 853 patients with lung
      cancer. Gene expression levels were compared between never and current smokers,
      and time-dependent changes in gene expression were studied in former smokers. A
      total of 3,223 transcripts were differentially expressed between smoking groups
      in the discovery set (n = 344, P < 1.29 * 10(-6)). A substantial number of
      smoking-induced genes also were validated in two replication sets (n = 285 and
      224), and a gene expression signature of 599 transcripts consistently segregated
      never from current smokers across all three sets. The expression of the majority
      of these genes reverted to never-smoker levels following smoking cessation,
      although the time course of normalization differed widely among transcripts.
      Moreover, some genes showed very slow or no reversibility in expression,
      including SERPIND1, which was found to be the most consistent gene permanently
      altered by smoking in the three sets. Our findings therefore indicate that
      smoking deregulates many genes, many of which reverse to normal following smoking
      cessation. However, a subset of genes remains altered even decades following
      smoking cessation and may account, at least in part, for the residual risk of
      lung cancer among former smokers. Cancer Res; 72(15); 3753-63. (c)2012 AACR.

PMID- 22659452
TI  - Inhibitory roles of signal transducer and activator of transcription 3 in
      antitumor immunity during carcinogen-induced lung tumorigenesis.
AB  - Stat3 mediates a complex spectrum of cellular responses, including inflammation,
      cell proliferation, and apoptosis. Although evidence exists in support of a
      positive role for Stat3 in cancer, its role has remained somewhat controversial
      because of insufficient study of how its genetic deletion may affect
      carcinogenesis in various tissues. In this study, we show using epithelium
      specific knockout mice (Stat3(Delta/Delta)) that Stat3 blunts rather than
      supports antitumor immunity in carcinogen-induced lung tumorigenesis. Although
      Stat3(Delta/Delta) mice did not show any lung defects in terms of proliferation,
      apoptosis, or angiogenesis, they exhibited reduced urethane-induced tumorigenesis
      and increased antitumor inflammation and natural killer (NK) cell immunity.
      Comparative microarray analysis revealed an increase in Stat3(Delta/Delta) tumors
      in proinflammatory chemokine production and a decrease in MHC class I antigen
      expression associated with NK cell recognition. Consistent with these findings,
      human non-small cell lung cancer (NSCLC) cells in which Stat3 was silenced
      displayed an enhancement of proinflammatory chemokine production, reduced
      expression of MHC class I antigen, and increased susceptibility to NK cell
      mediated cytotoxicity. In addition, supernatants from Stat3-silenced NSCLC cells
      promoted monocyte migration. Collectively, our findings argue that Stat3 exerts
      an inhibitory effect on antitumor NK cell immunity in the setting of carcinogen
      induced tumorigenesis.

PMID- 22659453
TI  - Vav3-rac1 signaling regulates prostate cancer metastasis with elevated Vav3
      expression correlating with prostate cancer progression and posttreatment
      recurrence.
AB  - Prostate cancer remains the second leading cause of cancer death in men in the
      Western world. Yet current therapies do not significantly improve the long-term
      survival of patients with distant metastasis. In this study, we investigated the
      role of the guanine nucleotide exchange factor Vav3 in prostate cancer
      progression and metastasis and found that Vav3 expression correlated positively
      with prostate cancer cell migration and invasion. Stimulation of the receptor
      tyrosine kinase EphA2 by ephrinA1 resulted in recruitment and tyrosine
      phosphorylation of Vav3, leading to Rac1 activation as well as increased
      migration and invasion in vitro. Reduction of Vav3 resulted in fewer para-aortic
      lymph nodes and bone metastasis in vivo. Clinically, expression of Vav3 and EphA2
      was elevated in late-stage and metastatic prostate cancers. Among patients with
      stage IIB or earlier prostate cancer, higher Vav3 expression correlated with
      lower cumulative biochemical failure-free survival, suggesting that Vav3 may
      represent a prognostic marker for posttreatment recurrence of prostate cancer.
      Together, our findings provide evidence that the Vav3-mediated signaling pathway
      may serve as a therapeutic target for prostate cancer metastasis.

PMID- 22659454
TI  - Targeting of a conformationally exposed, tumor-specific epitope of EGFR as a
      strategy for cancer therapy.
AB  - Epidermal growth factor receptor (EGFR) and its most common extracellular mutant,
      EGFRvIII, are important therapeutic targets in multiple cancer types. A number of
      monoclonal antibodies and small-molecule inhibitors against these receptors are
      now used for anticancer treatments. New insights into the structure and function
      of these receptors illustrate how they can be targeted in novel ways, with
      expected improvements in the therapeutic efficacy. Monoclonal antibody 806
      (mAb806) is an antibody that targets a conformationally exposed epitope of wild
      type EGFR when it is overexpressed on tumor cells or in the presence of oncogenic
      mutations such as EGFRvIII. The mechanism of action of mAb806, which allows for
      EGFR inhibition without normal tissue toxicity, creates opportunities for
      combination therapy and strongly suggests mAb806 will be a superior targeted
      delivery system for antitumor agents. Targeting of the epitope for mAb806 also
      appears to be an improved strategy to inhibit tumors that express EGFRvIII. This
      concept of conformational epitope targeting by antibodies reflects an underlying
      interplay between the structure and biology of different conformational forms of
      the EGFR family.

PMID- 22659456
TI  - Dishonorable discharge: the oncogenic roles of cleaved E-cadherin fragments.
AB  - Strong cell-cell interactions represent a major barrier against cancer cell
      mobility, and loss of intercellular adhesion by E-cadherin is a fundamental
      change that occurs during the progression of cancer to invasive disease. However,
      some aggressive carcinomas retain characteristics of differentiated epithelial
      cells, including E-cadherin expression. Emerging evidence indicates that
      proteolysis of E-cadherin generates fragments that promote tumor growth,
      survival, and motility, suggesting that E-cadherin cleavage converts this tumor
      suppressor into an oncogenic factor. In this review we discuss the emerging roles
      of cleaved E-cadherin fragments as modulators of cancer progression, and explore
      the translational and clinical implications of this research.

PMID- 22659458
TI  - Environmental control of daily stem growth patterns in five temperate broad
      leaved tree species.
AB  - Tree ring analysis investigates growth processes at time horizons of several
      weeks to millennia, but lacks the detail of short-term fluctuation in cambial
      activity. This study used electronic high-precision dendrometry for analyzing the
      environmental factors controlling stem diameter variation and radial growth in
      daily resolution in five co-existing temperate broad-leaved tree species (genera
      Fraxinus, Acer, Carpinus, Tilia and Fagus) with different growth and survival
      strategies. Daily stem radius change (SRC(d)) was primarily influenced by the
      atmospheric demand for water vapor (expressed either as vapor pressure deficit
      (D) or relative air humidity (RH)) while rainfall, soil matrix potential,
      temperature and radiation were only secondary factors. SRC(d) increased linearly
      with increasing RH and decreasing D in all species. The positive effect of a low
      atmospheric water vapor demand on SRC(d) was largest in June during the period of
      maximal radial growth rate and persisted when observation windows of 7 or 21 days
      instead of 1 day were used. We found a high synchronicity in the day-to-day
      growth rate fluctuation among the species with increment peaks corresponding to
      air humidity maxima, even though the mean daily radial growth rate differed
      fivefold among the species. The five -species also differed in the positive slope
      of the growth/RH relationship with the steepest increase found in Fraxinus and
      the lowest in Fagus. We explain the strong positive effect of high RH and low D
      on radial stem increment by lowered transpiration which reduces negative pressure
      in the conducting system and increases turgor in the stem cambium cells, thereby
      favoring cell division and expansion. The results suggest that mechanistic models
      of tree growth need to consider the atmospheric water status in addition to the
      known controlling environmental factors: temperature, soil moisture and
      precipitation. The results further have implications for sensitivity analyses of
      tree growth to climatic changes.

PMID- 22659459
TI  - Novel, cyclic heat dissipation method for the correction of natural temperature
      gradients in sap flow measurements. Part 2. Laboratory validation.
AB  - Sap flow measurements conducted with thermal dissipation probes (TDPs) are
      vulnerable to natural temperature gradient (NTG) bias. Few studies, however,
      attempted to explain the dynamics underlying the NTG formation and its influence
      on the sensors' signal. This study focused on understanding how the TDP signals
      are affected by negative and positive temperature influences from NTG and tested
      the novel cyclic heat dissipation (CHD) method to filter out the NTG bias. A
      series of three experiments were performed in which gravity-driven water flow was
      enforced on freshly cut stem segments of Fagus sylvatica L., while an artificial
      temperature gradient (ATG) was induced. The first experiment sought to confirm
      the incidence of the ATG on sensors. The second experiment established the mis
      estimations caused by the biasing effect of the ATG on standard TDP measurements.
      The third experiment tested the accuracy of the CHD method to account for the ATG
      biasing effect, as compared with other cyclic correction methods. During
      experiments, sap flow measured by TDP was assessed against gravimetric
      measurements. The results show that negative and positive ATGs were comparable in
      pattern but substantially larger than field NTGs. Second, the ATG bias caused an
      overestimation of the standard TDP sap flux density of ~17 cm(3) cm(-2) h(-1) by
      76%, and the sap flux density of ~2 cm(3) cm(-2) h(-1) by over 800%. Finally, the
      proposed CHD method successfully reduced the max. ATG bias to 25% at ~11 cm(3)
      cm(-2) h(-1) and to 40% at ~1 cm(3) cm(-2) h(-1). We concluded that: (i) the TDP
      method is susceptible to NTG especially at low flows; (ii) the CHD method
      successfully corrected the TDP signal and resulted in generally more accurate sap
      flux density estimates (mean absolute percentage error ranging between 11 and
      21%) than standard constant power TDP method and other cyclic power methods; and
      (iii) the ATG enforcing system is a suitable way of re-creating NTG for future
      tests.

PMID- 22659460
TI  - Differential effects of plant ontogeny and damage type on phloem and foliage
      monoterpenes in jack pine (Pinus banksiana).
AB  - Coniferous trees have both constitutive and inducible defences that deter or kill
      herbivores and pathogens. We investigated constitutive and induced monoterpene
      responses of jack pine (Pinus banksiana Lamb.) to a number of damage types: a
      fungal associate of the mountain pine beetle (Dendroctonus ponderosae Hopkins),
      Grosmannia clavigera (Robinson-Jeffrey & R.W. Davidson); two phytohormones,
      methyl jasmonate (MJ) and methyl salicylate (MS); simulated herbivory; and
      mechanical wounding. We only included the fungal, MJ and mechanical wounding
      treatments in the field experiments while all treatments were part of the
      greenhouse studies. We focused on both constitutive and induced responses between
      juvenile and mature jack pine trees and differences in defences between phloem
      and needles. We found that phytohormone applications and fungal inoculation
      resulted in the greatest increase in monoterpenes in both juvenile and mature
      trees. Additionally, damage types differentially affected the proportions of
      individual monoterpenes: MJ-treated mature trees had higher myrcene and beta
      pinene than fungal-inoculated mature trees, while needles of juveniles inoculated
      with the fungus contained higher limonene than MJ- or MS-treated juveniles.
      Although the constitutive monoterpenes were higher in the phloem of juveniles
      than mature jack pine trees, the phloem of mature trees had a much higher
      magnitude of induction. Further, induced monoterpene concentrations in juveniles
      were higher in phloem than in needles. There was no difference in monoterpene
      concentration between phytohormone applications and G. clavigera inoculation in
      mature trees, while in juvenile trees MJ was different from both G. clavigera and
      simulated herbivory in needle monoterpenes, but there was no difference between
      phytohormone applications and simulated herbivory in the phloem.

PMID- 22659461
TI  - Identification of novel glutathione transferases in Echinococcus granulosus. An
      evolutionary perspective.
AB  - Glutathione transferase enzymes (GSTs) constitute a major detoxification system
      in helminth parasites and have been related to the modulation of host immune
      response mechanisms. At least three different GSTs classes have been described in
      Platyhelminthes: Mu, Sigma and Omega. Mining the genome of Echinococcus
      multilocularis and the ESTs databases of Taenia solium and E. granulosus
      identified two new GSTs from the cestode E. granulosus, named EgGST2 and EgGST3.
      It also revealed that the Omega class of GSTs was absent from the Taenidae
      family. EgGST2 and EgGST3 are actively expressed in the parasite. In order to
      know the origin of these new GSTs, in silico analyses were performed. While
      EgGST2 is classified as belonging to the Sigma class, the data obtained for
      EgGST3 allowed a less clear interpretation. The study of the evolutionary
      relatedness based on the C-terminal domain sequence, gene structure conservation
      and three-dimensional structure predictions, suggests that EgGST3 is derived from
      the Platyhelminthes' Sigma-class cluster. Interestingly, the N-terminal domain
      displays some characteristic Omega-class residues, including a Cys residue that
      is likely to be involved in the catalytic mechanism. We discuss different
      evolutionary scenarios that could explain the observed patterns.

PMID- 22659463
TI  - Influence of spike lavender (Lavandula latifolia Med.) essential oil in the
      quality, stability and composition of soybean oil during microwave heating.
AB  - Lipids oxidation is one of the main factors leading to quality losses in foods.
      Its prevention or delay could be obtained by the addition of antioxidants. In
      this sense the present work intend to monitor the protective effects of Lavandula
      latifolia essential oil during soybean oil microwave heating. To achieve the
      proposed goal quality parameters (free acidity, peroxide value, specific
      coefficients of extinction and DeltaK), fatty acids profile, tocopherols and
      tocotrienols composition, antioxidant activity and oxidative stability were
      evaluated in soybean oil with and without spike lavender essential oils (EO)
      submitted to different microwave heating exposure times (1, 3, 5, 10 and 15 min;
      1000 Watt) with a standard domestic microwave equipment. Microwave heating
      induced severe quality and composition losses, mainly above 3 min of microwave
      heating, regardless the sample tested. However, spike lavender EO addition
      counteracts the oxidation comparatively to control oils, by presenting enhanced
      values in quality parameters. A higher protection in unsaturated fatty acids loss
      was also observed as well as a higher antioxidant activity and oxidative
      stability. The microwave heating effects were clearly different in the samples
      with essential oils addition, allowing discrimination from plain soybean oils by
      a principal component analysis, being also capable to discriminate the different
      heating times tested within each sample.

PMID- 22659462
TI  - Protective effects of Ganoderma lucidum spore on cadmium hepatotoxicity in mice.
AB  - The medicinal fungus Ganoderma lucidum has been shown to have hepatoprotective
      effects. G. lucidum contains triterpenes and polysaccharides, and the Sporoderm
      broken G. lucidum powder is particular beneficial. This study utilized G. lucidum
      spore to examine its effect on [Cd(II)]-induced hepatotoxicity in mice and the
      mechanism of the protection. Mice were pretreated with G. lucidum spore (0.1,
      0.5, and 1.0 g/kg, po, for 7 days), and subsequently challenged with a
      hepatotoxic dose of Cd(II) (3.7 mg/kg, ip). Liver injury was evaluated 8h later.
      G. lucidum spore protected against Cd(II)-induced liver injury in a dose
      dependent manner, as evidenced by serum alanine aminotransferase, aspartate
      aminotransferase and histopathology. To examine the mechanism of protection,
      subcellular distribution of Cd(II) was determined. G. lucidum spore decreased
      Cd(II) accumulation in hepatic nuclei, mitochondria, and microsomes, but
      increased Cd(II) distribution to the cytosol, where Cd(II) is sequestered by
      metallothionein, a protein against Cd(II) toxicity. Indeed, G. lucidum spore
      induced hepatic metallothionein-1 mRNA 8-fold, and also increased metallothionein
      protein as determined by the Cd(II)/hemoglobin assay. Cd(II)-induced oxidative
      stress was also decreased by G. lucidum spore, as evidenced by decreased
      formation of malondialdehyde. In summary, G. lucidum spore is effective in
      protection against Cd(II)-induced hepatotoxicity, and this effect is due, at
      least in part, to the induction of hepatic metallothionein to achieve beneficial
      effects.

PMID- 22659464
TI  - Effect of dietary inclusion of salt substitutes "Obu-Otoyo" on some biochemical
      indices in rat.
AB  - "Obu-Otoyo" in folklore has been used as salt substitutes in diet of patients for
      the management of hypertension with no report on its toxicological effects.
      Hence, this study sought to investigate the effect of dietary inclusion of two
      types of the salt substitutes (Obu-Otoyo): salt A and salt B on some biochemical
      indices in rats. The mineral content of the salt substitutes was determined and
      the salt substitutes were fed to normal rats as dietary inclusion (0.1-1.0%). The
      dietary inclusion of the salt substitutes caused a significant (P<0.05) increase
      in plasma activities of alkaline phosphatase (ALP), alanine transaminase (ALT),
      aspartate transaminase (AST), total bilirubin, and atherogenic lipids content
      (total cholesterol, LDL-cholesterol and triglyceride) with a concomitant decrease
      in the HDL-cholesterol content when compared with the control. Furthermore, the
      mineral determination of the salt substitutes revealed the presence of some toxic
      metals. The alterations in plasma activities of liver function enzymes and lipid
      profile in rat fed dietary inclusions of "Obu-Otoyo" may be related to the high
      content of some toxic/heavy metals in the salt substitutes. Therefore, this
      finding indicates that Obu-Otoyo is toxic to rat.

PMID- 22659465
TI  - The presence of monoiodinated derivates of daidzein and genistein in human urine
      and its effect on thyroid gland function.
AB  - Dietary supplements used by women during menopause are usually based on plant
      extracts containing isoflavonoids, daidzein and genistein. Genistein is a known
      inhibitor of many enzymes, including thyroid peroxidase (TPO). In the thyroid
      follicle, genistein acts as its alternate substrate for the formation of
      genistein iodinated derivatives. The aim of this study was to search for daidzein
      and genistein-iodinated derivatives in urine of isoflavonoid-supplemented women.
      Additionally, selected phytoestrogens, steroid and thyroid hormones before and
      after three months of phytoestrogen supplementation were estimated. Urinary
      levels of free phytoestrogen increased significantly after therapy. They ranged
      between 0.3-1600, 0.6-670 and 0-206 nmol/L for daidzein, genistein and S-equol,
      respectively. Monoiodinated derivatives of genistein were observed (0-504 pmol/L)
      in 60% of the investigated samples. Steroid and thyroid hormone levels were
      within the normal range and were not significantly altered. The presence of
      monoiodinated derivates in human urine confirmed that genistein and daidzein may
      enter human thyroid follicles and influence TPO. Since the levels of the free
      thyroid hormones were not affected, we propose that the use of phytoestrogen
      dietary supplements is not associated with the development of thyroid-gland
      disorders in subjects with adequate iodine intake.

PMID- 22659466
TI  - A physiologically relevant approach to characterize the microbial response to
      colloidal particles in food matrices within a simulated gastrointestinal tract.
AB  - Colloids on the nanometer size scale are beginning to find increased applications
      in drinks, foods, food-contact surfaces, and food packaging. While these
      particles add intrinsic value to the food industry, their potential toxicities
      warrant careful studies. The physicochemical changes and possible perturbations
      to microbial communities within the gastrointestinal tract have not been
      adequately studied. The purpose of this study was to design and perform a
      simulated digestion protocol to evaluate the effect of colloidal silver in an
      orange juice suspension when exposed to planktonic bacterial cultures and
      biofilms. The model system includes four precursor steps in which the silver is
      exposed to varying pH conditions and incubation times. The gastrointestinally
      "digested" samples were then incubated with Escherichia coli strains for up to
      4h, the average residence time of foods in the GI tract. The physicochemical
      changes of the colloids and their corresponding biological effects were
      characterized at every step. The results showed differences between (1) bacterial
      cultures versus bacterial biofilms, (2) "digested" versus "undigested" silver on
      bacteria, and (3) differences between "digested" silver nitrate versus silver
      colloids on bacteria. We conclude that simulated digestion, as well as manner in
      which bacterial cells are grown, influences the results of toxicity.

PMID- 22659467
TI  - Stem cell transplant for children with sickle cell anemia: parent and patient
      interest.
AB  - We describe adolescents' and parents' interest in hematopoietic stem cell
      transplant (HSCT) as a cure for sickle cell disease (SCD) and factors associated
      with increased interest. We administered a 40 question survey to assess the
      interest in HSCT in parents and adolescents with HBSS or HBSbeta(0) thalassemia.
      The survey tool assessed factors that may influence interest in HSCT including
      demographic data, disease severity, views on prognosis, and health-related
      quality of life (HRQOL). All participants were given a handout on the risks and
      benefits of an HSCT before completing the survey. One hundred twenty-nine parents
      and 59 adolescents completed the survey. Forty-five percent of parents (54 of
      119) would likely have their child undergo HSCT, and 35% of adolescents (19 of
      55) would likely undergo HSCT if it was recommended by their hematologist.
      Parents of adolescents, as well as adolescent patients with better HRQOL, were
      more interested in HSCT. Prior exchange transfusion was associated with increased
      interest in HSCT (62% [23 of 37] versus 38% [29 of 76]; P = .02). The majority of
      parents believe their child's SCD will get better (66%; [80 of 122]), will not
      likely prevent their child from achieving life goals (83%; [100 of 121]), and
      will not shorten their child's lifespan (86%; [102 of 119]). There is strong
      parent and adolescent interest in HSCT as a cure for SCD. It is concerning that
      few parents and adolescents believe SCD will negatively impact their prognosis.
      Education on the potential long-term sequelae of SCD is needed when considering
      the role for HSCT.

PMID- 22659468
TI  - Stromal fibroblasts synergize with hypoxic oxidative stress to enhance melanoma
      aggressiveness.
AB  - On the basis of recent advances indicating a key role of microenvironment for
      tumor progression, we investigated the role of fibroblasts, macrophages and
      hypoxia, for primary melanoma aggressiveness. Our data indicate a key role of
      hypoxia in stromal reactivity, acting on both myofibroblasts and machrophages
      differentiation. Hypoxic myofibroblasts are more active than macrophages in
      inducing melanoma invasiveness and exploit their oxidative stress due to hypoxia
      to secrete soluble factors favouring melanoma invasion and chemotaxis. We
      underscore the key role of microenviroment on melanoma malignancy, highlighting
      reactive fibroblasts, intratumoral hypoxia and oxidative stress as promising
      targets for melanoma antimetastatic strategies.

PMID- 22659469
TI  - Role of miR-132 in angiogenesis after ocular infection with herpes simplex virus.
AB  - MicroRNAs (miRNAs) are small regulatory molecules that control diverse biological
      processes that include angiogenesis. Herpes simplex virus (HSV) causes a chronic
      immuno-inflammatory response in the eye that may result in corneal
      neovascularization during blinding immunopathological lesion stromal keratitis
      (SK). miR-132 is a highly conserved miRNA that is induced in endothelial cells in
      response to growth factors, such as vascular endothelial growth factor (VEGF). In
      this study, we show that miR-132 expression was up-regulated (10- to 20-fold)
      after ocular infection with HSV, an event that involved the production of both
      VEGF-A and IL-17. Consequently, blockade of VEGF-A activity using soluble VEGF
      receptor 1 resulted in significantly lower levels of corneal miR-132 after HSV
      infection. In addition, low levels of corneal miR-132 were detected in IL-17
      receptor knockout mice after HSV infection. In vivo silencing of miR-132 by the
      provision of anti-miR-132 (antagomir-132) nanoparticles to HSV-infected mice led
      to reduced corneal neovascularization and diminished SK lesions. The anti
      angiogenic effect of antagomir-132 was reflected by a reduction in angiogenic Ras
      activity in corneal CD31-enriched cells (presumably blood vessel endothelial
      cells) during SK. To our knowledge, this is one of the first reports of miRNA
      involvement in an infectious ocular disease. Manipulating miRNA expression holds
      promise as a therapeutic approach to control an ocular lesion that is an
      important cause of human blindness.

PMID- 22659470
TI  - Highly invasive melanoma cells activate the vascular endothelium via an MMP
      2/integrin alphavbeta5-induced secretion of VEGF-A.
AB  - Tumor cell extravasation is a critical step in the metastatic cascade and
      requires interaction between the tumor cell and the endothelium. Although cancer
      progression depends on a complex network of mechanisms, including inflammation
      and coagulation, the involvement of tumor-induced endothelium activation and the
      subsequent release of procoagulatory factors in this process are not well
      understood. Using tissue sections from patients with malignant melanoma,
      immunofluorescence studies for the presence of von Willebrand factor (VWF)
      clearly demonstrated endothelium activation and the formation of ultra-large VWF
      fibers in these patients. In vitro analyses revealed that supernatants from
      highly invasive melanoma cells induced an acute endothelium activation measured
      by VWF, P-selectin, and angiopoietin-2 release. Proteome profiling identified
      vascular endothelial growth factor A (VEGF-A) as the main mediator of endothelium
      activation. Inhibition and knock-down of VEGF-A in melanoma cells led to a
      rigorous decrease in VWF exocytosis. Selective small-interfering RNA to matrix
      metalloproteinase-2 (MMP-2) inhibited endothelium activation, and this effect
      correlated with reduced VEGF-A content in the supernatants of melanoma cells.
      Further experiments showed that active MMP-2 regulates VEGF-A in melanoma cells
      on a transcriptional level via an integrin alphavbeta5/phosphoinositide-3-kinase
      dependent pathway. In conclusion, these results indicate an important role of
      VEGF-A in acute endothelium activation and provide clear evidence that MMP-2
      plays a pivotal role in the autocrine regulation of VEGF-A expression in melanoma
      cells.

PMID- 22659471
TI  - Re-exposure and environmental enrichment reveal NPY-Y1 as a possible target for
      post-traumatic stress disorder.
AB  - Exposure-based cognitive behavioral therapy in post-traumatic stress disorder
      (PTSD) patients relieves symptoms caused by fear association as well as symptoms
      that are not the result of associative learning. We used the inescapable foot
      shock model (IFS), an animal model for PTSD, to study the possible involvement of
      glutamate receptors, the corticotropin-releasing factor (CRF) system, and the
      neuropeptide Y (NPY) system in the reduction of stress sensitization following
      repeated re-exposure to the conditioning context. Starting one week after the IFS
      procedure, the rats were repeatedly re-exposed to the shock environment. Stress
      sensitivity was measured in a modified open field test (sudden silence was used
      as a stressor). Selected mRNAs (GluN1, -2A-C, GluA1-4, GluK1-5, CRF, CRF-R1, NPY,
      NPY-Y1) were quantified in the amygdala. Repeated re-exposure (RE) to the IFS
      context reduced both trauma-associated anxiety (to the IFS context) and the
      enhanced stress sensitivity (in the open field). Changes in glutamate receptor
      subunits (GluN1, GluN2A-B, GluA1, GluA4, GluK3, GluK4) were detected in the
      amygdala that were normalized by RE. However, infusion of the AMPA/kainate
      antagonist NBQX in the BLA (basolateral amygdala) did not improve the anxious
      behavior. RE normalized IFS-induced increases in CRF-R1 mRNA and increased NPY-Y1
      mRNA expression in the amygdala. Previously, and repeated here, we showed that
      environmental enrichment (EE) enhances recovery from IFS. EE led to similar
      changes in CRF-R1 and NPY-Y1 expression as RE did. Importantly, administration of
      [Leu31, Pro34]-NPY (Y1 agonist) in the BLA normalized the enhanced sensitivity to
      stress after IFS. Our data suggest that the NPY-Y1 receptor in the amygdala may
      serve as a therapeutic target for the treatment of PTSD.

PMID- 22659472
TI  - The nicotinic alpha7 receptor agonist GTS-21 improves cognitive performance in
      ketamine impaired rhesus monkeys.
AB  - The cognitive deficits associated with schizophrenia are recognized as a core
      component of the disorder, yet there remain no available therapeutics to treat
      these symptoms of the disease. As a result, there is a need for establishing
      predictive preclinical models to identify the therapeutic potential of novel
      compounds. In the present study, rhesus monkeys were trained in the object
      retrieval-detour task, which is dependent on the prefrontal cortex, a brain
      region implicated in the cognitive deficits associated with schizophrenia. The
      NMDA receptor antagonist ketamine significantly impaired performance without
      affecting measures of motor or visuospatial abilities. Pre-treatment with the
      nicotinic alpha7 agonist GTS-21 (0.03 mg/kg) significantly attenuated the
      ketamine-induced impairment, consistent with reports from clinical trials
      suggesting that nicotinic alpha7 receptor agonism has pro-cognitive potential in
      clinical populations. In contrast, pretreatment with the acetylcholinesterase
      inhibitor donepezil failed to reverse the ketamine-induced impairment, consistent
      with studies showing a lack of pro-cognitive effects in patients with
      schizophrenia. These data suggest that the ketamine-impaired object retrieval
      detour task could provide a model with improved predictive validity for drug
      development, and confirm the need for additional efforts in back-translation.
      This article is part of a Special Issue entitled 'Cognitive Enhancers'.

PMID- 22659473
TI  - Molecular mechanisms that desensitize metabotropic glutamate receptor signaling:
      an overview.
AB  - The purpose of the present article is to review our actual knowledge on the
      desensitization of metabotropic glutamate receptors based on the literature
      available so far, with the attempt to emphasize all converging data and to give a
      possible explanation to those evidences that still remain controversial. 1. We
      review our knowledge on the regulation of mGlu receptors based on the available
      literature 2. We report converging data and we comment on issues that still
      remain controversial. This article is part of a Special Issue entitled
      'Metabotropic Glutamate Receptors'.

PMID- 22659474
TI  - The effect of nap frequency on daytime sleep architecture.
AB  - It is well documented that the quality and quantity of prior sleep influence
      future sleep. For instance, nocturnal sleep restriction leads to an increase in
      slow wave sleep (SWS) (i.e. SWS rebound) during a subsequent sleep period.
      However, few studies have examined how prior napping affects daytime sleep
      architecture. Because daytime naps are recommended for management of disrupted
      sleep, understanding the impact of napping on subsequent sleep may be important.
      We monitored sleep-wake patterns for one week with actigraphy followed by a 75
      minute polysomnographically-recorded nap. We found that greater nap frequency was
      correlated with increased Stage 1 and decreased SWS. We categorized subjects
      based on nap frequency during the prior week (0 nap, 1 to 2 naps, and 3 to 4
      naps) and found differences in Stage 1, Stage 2, and SWS between groups. Subjects
      who took no naps had the greatest amount of SWS, those who took 1 to 2 naps had
      the most Stage 2 sleep, and those who took 3 to 4 naps had the most Stage 1.
      While correlations were not found between nap frequency and nocturnal sleep
      measures, frequent napping was associated with increased subjective sleepiness.
      Therefore, frequent napping appears to be associated with lighter daytime sleep
      and increased sleepiness during the day. Speculatively, low levels of daytime
      sleepiness and increased SWS in non-nappers may help explain why these
      individuals choose not to nap.

PMID- 22659475
TI  - Different chemical fractions of fetal fluids account for their attractiveness at
      parturition and their repulsiveness during late-gestation in the ewe.
AB  - We have investigated whether the chemical components of fetal fluids (FFs), which
      elicit repulsion in late gestating ewes, are also those responsible for the
      attractiveness of fetal fluids at parturition. An aqueous fraction of FFs (A1),
      obtained after extraction with hexane, was tested for repulsion in late-pregnant
      ewes and for attraction at parturition. We also investigated if the repulsive and
      attractive characteristics of this A1 fraction were maintained after an
      additional extraction with dichloromethane (DCM, CH(2)Cl(2)) that produced two
      more fractions (aqueous/high polarity: A2 and dichloromethane/medium polarity:
      DCM). Thus, late-pregnant ewes were tested for repulsion of aqueous extracts of
      FFs (A1, A2 and DCM fractions) in a two-choice test of food preference, whereas
      parturient ewes were tested for attraction toward these same fractions in a two
      choice test of licking warm spongy cloths. The A1 fraction was repulsive to late
      pregnant ewes and attractive to parturient females. In contrast, neither the A2
      nor the DCM fractions were repulsive to late-pregnant ewes, whereas both
      fractions were attractive to parturient ones. The discordance between the
      repulsive and attractive properties of the A2 and DCM fractions suggests that the
      attractiveness of FFs for parturient ewes and its repulsiveness for females
      outside the peripartum period depend on mixtures of substances that are at least
      partially different. Some compounds with high and medium polarity in the A2 and
      DCM fractions would act synergistically to generate the repulsiveness of FFs,
      whereas both high and medium polarity compounds can evoke attraction
      independently of each other.

PMID- 22659476
TI  - Neurophysiological correlates of age-related changes in working memory updating.
AB  - Normal aging is associated with a gradual decline in executive functions such as
      set-shifting, inhibition, and updating, along with a progressive decline of
      neurotransmitter systems including the dopamine system. Modulation from the
      dopamine system is thought to be critical for the gating of information during
      working memory. Given the known relationships between executive aging, cognition,
      and dopamine, this study aims to explore the neurobiology underlying age-related
      changes in working memory updating using fMRI with healthy subjects from across
      the adult age spectrum. Our results indicate that older age is associated with
      poorer performance, reduced meso-cortico-striatal activation, and reduced
      functional coupling between the caudate and the VLPFC during the updating task.
      Additionally, caudate activation is associated with improved accuracy and VLPFC
      activation with faster reaction times in the full sample. Thus, older subjects'
      under-recruitment of and reduced functional coupling between these regions may
      specifically underlie age-related changes in working memory updating. These
      results are consistent with computational models of executive cognition and
      dopamine-mediated age-related cognitive decline.

PMID- 22659477
TI  - The intrinsic connectivity distribution: a novel contrast measure reflecting
      voxel level functional connectivity.
AB  - Resting-state fMRI (rs-fMRI) holds promise as a clinical tool to characterize and
      monitor the phenotype of different neurological and psychiatric disorders. The
      most common analysis approach requires the definition of one or more regions-of
      interest (ROIs). However this need for a priori ROI information makes rs-fMRI
      inadequate to survey functional connectivity differences associated with a range
      of neurological disorders where the ROI information may not be available. A
      second problem encountered in fMRI measures of connectivity is the need for an
      arbitrary correlation threshold to determine whether or not two areas are
      connected. This is problematic because in many cases the differences in tissue
      connectivity between disease groups and/or control subjects are threshold
      dependent. In this work we propose a novel voxel-based contrast mechanism for rs
      fMRI, the intrinsic connectivity distribution (ICD), that neither requires a
      priori information to define a ROI, nor an arbitrary threshold to define a
      connection. We show the sensitivity of previous methods to the choice of
      connection thresholds and evaluate ICD using a survey study comparing young
      adults born prematurely to healthy term control subjects. Functional connectivity
      differences were found in hypothesized language processing areas in the left
      temporal-parietal areas. In addition, significant clinically-relevant differences
      were found between preterm and term control subjects, highlighting the importance
      of whole brain surveys independent of a priori information.

PMID- 22659478
TI  - Processing of vocalizations in humans and monkeys: a comparative fMRI study.
AB  - Humans and many other animals use acoustical signals to mediate social
      interactions with conspecifics. The evolution of sound-based communication is
      still poorly understood and its neural correlates have only recently begun to be
      investigated. In the present study, we applied functional MRI to humans and
      macaque monkeys listening to identical stimuli in order to compare the cortical
      networks involved in the processing of vocalizations. At the first stages of
      auditory processing, both species showed similar fMRI activity maps within and
      around the lateral sulcus (the Sylvian fissure in humans). Monkeys showed
      remarkably similar responses to monkey calls and to human vocal sounds (speech or
      otherwise), mainly in the lateral sulcus and the adjacent superior temporal gyrus
      (STG). In contrast, a preference for human vocalizations and especially for
      speech was observed in the human STG and superior temporal sulcus (STS). The STS
      and Broca's region were especially responsive to intelligible utterances. The
      evolution of the language faculty in humans appears to have recruited most of the
      STS. It may be that in monkeys, a much simpler repertoire of vocalizations
      requires less involvement of this temporal territory.

PMID- 22659479
TI  - Cortical dynamics of human scalp EEG origins in a visually guided motor
      execution.
AB  - The EEG mu rhythm is often used as an index of activation in the sensorimotor
      cortex. However, the blur caused by volume conduction makes it difficult to
      identify the exact origin of the EEG rhythm in the brain using only the human
      scalp EEG. In this study, simultaneous fMRI and EEG measurements were performed
      during a visually guided motor execution task in order to investigate whether the
      mu rhythm in the scalp EEG is an indication of the activity in the sensorimotor
      cortex. In addition, a new method was proposed for reconstruction of the cortical
      EEG activity through the fusion of fMRI and EEG data. A suppression of mu rhythm
      appeared around the lateral central electrode sites, just above the sensorimotor
      cortex, in association with the activity in that region. During a visually guided
      motor execution task, the alpha rhythms at the occipital electrode sites and the
      alpha rhythm at the central electrode sites also showed a correlation with the
      fMRI signal in the occipital and the supplementary motor cortices, respectively.
      This method allows the investigation of the scalp EEG origin with the spatial
      precision of fMRI, while retaining dynamic properties of the cortex with the
      temporal precision of EEG.

PMID- 22659480
TI  - Grammar learning in older adults is linked to white matter microstructure and
      functional connectivity.
AB  - Age-related decline in cognitive function has been linked to alterations of white
      matter and functional brain connectivity. With regard to language, aging has been
      shown to be associated with impaired syntax processing, but the underlying
      structural and functional correlates are poorly understood. In the present study,
      we used an artificial grammar learning (AGL) task to determine the ability to
      extract grammatical rules from new material in healthy older adults. White matter
      microstructure and resting-state functional connectivity (FC) of task-relevant
      brain regions were assessed using multimodal magnetic resonance imaging (MRI).
      AGL performance correlated positively with fractional anisotropy (FA) underlying
      left and right Brodmann areas (BA) 44/45 and in tracts originating from left BA
      44/45. An inverse relationship was found between task performance and FC of left
      and right BA 44/45, linking lower performance to stronger inter-hemispheric
      functional coupling. Our results suggest that white matter microstructure
      underlying specific prefrontal regions and their functional coupling affect
      acquisition of syntactic knowledge in the aging brain, offering further insight
      into mechanisms of functional decline in older adults.

PMID- 22659481
TI  - Noninvasive optical evaluation of spontaneous low frequency oscillations in
      cerebral hemodynamics.
AB  - Spontaneous low frequency oscillations (LFOs) around 0.1 Hz have been observed in
      mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV). Previous
      studies have shown that cerebral autoregulation in major arteries can be assessed
      by quantification of the phase shift between LFOs of MAP and CBFV. However, many
      cerebral diseases are associated with abnormal microvasculature and tissue
      dysfunction in brain, and quantification of these abnormalities requires direct
      measurement of cerebral tissue hemodynamics. This pilot study used a novel hybrid
      near-infrared diffuse optical instrument to noninvasively and simultaneously
      detect LFOs of cerebral blood flow (CBF) and cerebral oxygenation (i.e.,
      oxygenated/deoxygenated/total hemoglobin concentration: [HbO(2)]/[Hb]/THC) in
      human prefrontal cortex. Using the hybrid instrument and a finger plethysmograph,
      the dynamic changes of CBF, [HbO(2)], [Hb], THC and MAP were concurrently
      measured in 15 healthy subjects at rest, during 70 degrees  head-up-tilting (HUT)
      and during enforced breathing at 0.1 Hz. The LFOs were extracted from the
      measured variables using power spectral analysis, and the phase shifts and
      coherences of LFOs between MAP and each of the measured hemodynamic variables
      were calculated from the corresponding transfer functions. Levels of coherence
      (>0.4) were used to judge the success of LFO measurements. We found that CBF,
      [HbO(2)] and THC were reliable hemodynamic parameters in detecting LFOs and HUT
      was the most robust and stable protocol for quantifying phase shifts of
      hemodynamic LFOs. Comparing with other relevant studies, similar success rates
      for detecting cerebral LFOs have been achieved in our study. The phase shifts of
      LFOs in CBF were also close to those in CBFV reported by other groups, although
      the results in cerebral oxygenation measurements during enforced breathing varied
      across studies. Future study will investigate cerebral LFOs in patients with
      cerebral impairment and evaluate their cerebral autoregulation capabilities and
      neurocognitive functions via the quantification of LFO phase shifts.

PMID- 22659482
TI  - Quantitative susceptibility mapping for investigating subtle susceptibility
      variations in the human brain.
AB  - Quantitative susceptibility mapping (QSM) is a novel magnetic resonance-based
      technique that determines tissue magnetic susceptibility from measurements of the
      magnetic field perturbation. Due to the ill-posed nature of this problem,
      regularization strategies are generally required to reduce streaking artifacts on
      the computed maps. The present study introduces a new algorithm for calculating
      the susceptibility distribution utilizing a priori information on its regional
      homogeneity derived from gradient echo phase images and analyzes the impact of
      erroneous a priori information on susceptibility map fidelity. The algorithm,
      Homogeneity Enabled Incremental Dipole Inversion (HEIDI), was investigated with a
      special focus on the reconstruction of subtle susceptibility variations in a
      numerical model and in volunteer data and was compared with two recently
      published approaches, Thresholded K-space Division (TKD) and Morphology Enabled
      Dipole Inversion (MEDI). HEIDI resulted in susceptibility maps without streaking
      artifacts and excellent depiction of subtle susceptibility variations in most
      regions. By investigating HEIDI susceptibility maps acquired with the volunteers'
      heads in different orientations, it was demonstrated that the apparent magnetic
      susceptibility distribution of human brain tissue considerably depends on the
      direction of the main magnetic field.

PMID- 22659483
TI  - Quantification of dopamine D(2/3) receptors in rat brain using factor analysis
      corrected [18F]Fallypride images.
AB  - The goal of this work is to quantify the binding parameters of [(18)F]Fallypride
      in the striatal and extrastriatal regions of the rat brain using factor analysis
      (FA) to correct small animal PET kinetic imaging for spillover defluorination
      radioactivity. Eleven rats were employed for YAP-(S)PET acquisitions and
      metabolite studies. All kinetic parameters including B'(max) and K(d)V(R) were
      estimated with a three-tissue compartment seven-parameter model (3T-7k) on the
      basis of all the FA-corrected data from the multi-injection protocol. Binding
      potential (BP(ND)) was calculated with Logan's graphical analysis taking
      cerebellum as the reference region and using the first injection raw (BP(ND-RAW))
      and FA-corrected (BP(ND-FA)) data. Three distinct factors corresponding to
      free+non-specific binding, specific binding and skull and gland accumulation were
      recovered from FA with their corresponding spatial distributions. The resulting
      reconstructed images without skull and gland accumulation were improved to
      provide a better contrast between specific and non-specific regions. Very bad
      fits were obtained when using time-activity curves (TACs) calculated from the raw
      [(18)F]Fallypride data, whereas all TACs were well fitted by the 3T-7k model
      after FA correction. FA-corrected data enables the cerebellar region to be used
      as reference for the Logan approach. The magnitude of the BP(ND-FA) values was
      increased from 21% to 108% across regions and the rank order of BP(ND-FA) values
      (Cx<Hip<MB~Thal<VST<DST) matched those of B'(max) values. This [(18)F]Fallypride
      study in rats shows that all brain regions are contaminated by skull and gland
      radioactivity accumulation. We show that FA is a very effective method of
      correcting kinetic data for spillover activity. Moreover, the approach presented
      here with [(18)F]Fallypride data can be extended to other radioligands and also
      to human data which can be highly distorted by radiodefluorination as shown in
      the literature.

PMID- 22659484
TI  - Parallel-transmission-enabled magnetization-prepared rapid gradient-echo T1
      weighted imaging of the human brain at 7 T.
AB  - One of the promises of Ultra High Field (UHF) MRI scanners is to bring finer
      spatial resolution in the human brain images due to an increased signal to noise
      ratio. However, at such field strengths, the spatial non-uniformity of the Radio
      Frequency (RF) transmit profiles challenges the applicability of most MRI
      sequences, where the signal and contrast levels strongly depend on the flip angle
      (FA) homogeneity. In particular, the MP-RAGE sequence, one of the most commonly
      employed 3D sequences to obtain T1-weighted anatomical images of the brain, is
      highly sensitive to these spatial variations. These cause deterioration in image
      quality and complicate subsequent image post-processing such as automated tissue
      segmentation at UHF. In this work, we evaluate the potential of parallel
      transmission (pTx) to obtain high-quality MP-RAGE images of the human brain at 7
      T. To this end, non-selective transmit-SENSE pulses were individually tailored
      for each of 8 subjects under study, and applied to an 8-channel transmit-array.
      Such RF pulses were designed both for the low-FA excitation train and the 180
      degrees  inversion preparation involved in the sequence, both utilizing the
      recently introduced k(T)-point trajectory. The resulting images were compared
      with those obtained from the conventional method and from subject-specific RF
      shimmed excitations. In addition, four of the volunteers were scanned at 3 T for
      benchmarking purposes (clinical setup without pTx). Subsequently, automated
      tissue classification was performed to provide a more quantitative measure of the
      final image quality. Results indicated that pTx could already significantly
      improve image quality at 7 T by adopting a suitable RF-Shim. Exploiting the full
      potential of the pTx-setup, the proposed k(T)-point method provided excellent
      inversion fidelity, comparable to what is commonly only achievable at 3 T with
      energy intensive adiabatic pulses. Furthermore, the cumulative energy deposition
      was simultaneously reduced by over 40% compared to the conventional adiabatic
      inversions. Regarding the low-FA k(T)-point based excitations, the FA uniformity
      achieved at 7 T surpassed what is typically obtained at 3 T. Subsequently,
      automated white and gray matter segmentation not only confirmed the expected
      improvements in image quality, but also suggests that care should be taken to
      properly account for the strong local susceptibility effects near cranial
      cavities. Overall, these findings indicate that the k(T)-point-based pTx solution
      is an excellent candidate for UHF 3D imaging, where patient safety is a major
      concern due to the increase of specific absorption rates.

PMID- 22659485
TI  - Awareness modulates responses of the amygdala and the visual cortex to highly
      arousing visual threat.
AB  - It is still a matter of debate under which conditions the neural processing of
      emotional stimuli can occur without conscious awareness. Using functional
      magnetic resonance imaging, we investigated brain responses to highly arousing
      threat-related versus neutral pictures which were presented very briefly during
      two backward-masking conditions resulting in either subliminal or supraliminal
      stimulus processing. Signal detection analysis confirmed the successful
      experimental manipulation of awareness that effectively prevented stimulus
      recognition during the subliminal condition. Participants showed stronger
      responses of the amygdala and extrastriate visual cortex during the supraliminal,
      but not during the subliminal condition. These results suggest that the
      processing of highly arousing visual threat requires conscious awareness during
      backward masking. This contradicts the assumption of pervasive neural responses
      to emotional stimuli.

PMID- 22659486
TI  - Pre- and post-stimulus alpha activity shows differential modulation with spatial
      attention during the processing of pain.
AB  - Extensive work using magneto- and electroencephalography (M/EEG) suggests that
      cortical alpha activity represents a top-down controlled gating mechanism
      employed by processes like attention across different modalities. However, it is
      not yet clear to what extent this presumed gating function of alpha activity also
      applies to the processing of pain. In the current study, a spatial attention
      paradigm was employed requiring subjects to attend to painful laser stimuli on
      one hand while ignoring stimuli on the other hand. Simultaneously, brain activity
      was recorded with MEG. In order to disentangle pre- and post-stimulus effects of
      attention, alpha activity was analyzed during time windows in anticipation of and
      in response to painful laser stimulation. Painful laser stimuli led to a
      suppression of alpha activity over both ipsi- and contralateral primary
      somatosensory areas irrespective if they were attended or ignored. Spatial
      attention was associated with a lateralization of anticipatory pre-stimulus alpha
      activity. Alpha activity was lower over primary somatosensory areas when the
      contralateral hand was attended compared to when the ipsilateral hand was
      attended, in line with the notion that oscillatory alpha activity regulates the
      flow of incoming information by engaging and/or disengaging early sensory areas.
      On the contrary, post-stimulus alpha activity, for stimuli on either hand, was
      consistently decreased with attention over contralateral areas. Most likely, this
      finding reflects an increased cortical activation and enhanced alerting if a
      painful stimulus is attended. The present results show that spatial attention
      results in a modulation of both pre- and post-stimulus alpha activity associated
      with pain. This flexible regulation of alpha activity matches findings from other
      modalities. We conclude that the assumed functional role of alpha activity as a
      top-down controlled gating mechanism includes pain processing and most likely
      represents a unified mechanism used throughout the brain.

PMID- 22659487
TI  - Bronchodilators modulate inflammation in chronic obstructive pulmonary disease
      subjects.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by neutrophilic
      airway inflammation and oxidative stress. Leukotriene B4 (LTB4), a potent
      proinflammatory mediator, is synthesized by 5-lipoxygenase (5-LO), which is
      activated by the presence of lipid hydroperoxides resulting from oxidative stress
      on biological membranes. We proposed to evaluate the effect of a four week
      treatment with two different bronchodilators of common practice in COPD
      treatment, on the production of reactive oxygen species (ROS), in particular
      superoxide anions, and of LTB4 by peripheral blood neutrophils obtained from COPD
      subjects. 24 subjects among the COPD outpatients were enrolled, and randomized to
      receive either formoterol (12 MUg bid) or tiotropium (18 MUg od). Peripheral
      blood neutrophils were obtained at the start and at the end of the treatment, and
      production of superoxide anions and of LTB4 were evaluated as previously
      published. The results obtained showed a decrease in the unstimulated production
      of superoxide by isolated neutrophils in both groups, but tiotropium only was
      effective in modulating the production of LTB4, while formoterol caused an
      increased production of superoxide in response to fMLP, when compared to values
      obtained before treatment. In conclusion, tiotropium showed a better
      antiinflammatory activity profile when compared to formoterol in a clinical
      setting, reducing superoxide and LTB4 production by peripheral neutrophils
      obtained from COPD subjects.

PMID- 22659488
TI  - Vector replication and expression of HIV-1 antigens by the HIV/AIDS vaccine
      candidate MVA-B is not affected by HIV-1 protease inhibitors.
AB  - MVA-B is an attenuated poxvirus vector expressing human immunodeficiency virus
      type 1 Env, Gag, Pol, and Nef antigens from clade B, and is considered a
      promising HIV/AIDS vaccine candidate. Recently, a phase I clinical trial in human
      healthy volunteers has shown that MVA-B is safe and highly immunogenic, inducing
      broad, polyfunctional, and long-lasting CD4(+) and CD8(+) T cell responses to HIV
      1 antigens, with preference for effector memory T cells; and it also triggers the
      induction of specific antibodies to Env in most of the vaccines. While MVA
      recombinants expressing HIV-1 antigens are being used or plan to use in
      therapeutic clinical trials, little is known on the effect of HIV-1 highly active
      antiretroviral therapy in MVA life cycle. To define this role, here we have
      evaluated in established cell cultures and human dendritic cells to what extent
      different HIV-1 protease inhibitors affect virus replication and expression of
      HIV-1 antigens during MVA-B infection. The results obtained revealed that the
      most commonly used HIV-1 protease inhibitors (atazanavir, ritonavir, and
      lopinavir) had no effect on MVA-B virus growth kinetics, even at higher
      concentrations than those normally used on HAART. Furthermore, expression of
      gp120 and the fused Gag-Pol-Nef polyprotein in permissive and non-permissive
      cells infected with MVA-B were also not affected. These findings are relevant
      information for the therapeutic use of MVA-B as an HIV-1/AIDS vaccine.

PMID- 22659489
TI  - Antigenic characteristics of the complete and truncated capsid protein VP1 of
      enterovirus 71.
AB  - The complete VP1 protein of enterovirus 71 (EV71) and a series of truncations
      were expressed in Escherichia coli and their antigenic characteristics were
      studied. Immunoblot analysis showed the major immunoreactive region of the VP1
      protein was located in the N-terminal portion at position of amino acid (aa) 1
      100. The complete VP1 possessed strong cross-reactivity with antisera against
      coxsackievirus A16 (CA16) and echovirus 6 (Echo6), while the truncated fragment
      at position 1-100 aa only had weak cross-reactivity. Moreover, an EV71-specific
      linear epitope at position 94-105 aa was identified using two EV71-specific mAbs
      (2B9 and 5B7) with indirect ELISA, but could not be recognized by antibodies
      against EV71 virus particles. The complete and all of truncated VP1 proteins
      except His-VP1(202-297) and GST-VP1(202-248) failed to elicit a significant
      neutralizing antibody response in mice. His-VP1(202-297) and GST-VP1(202-248)
      containing neutralizing epitope(s) could be recognized only by anti-EV71 mouse
      sera but not rabbit or human sera. These findings may contribute to a further
      understanding of antigenic characteristics of the capsid protein VP1 and may be
      helpful to the development of diagnostic reagents and vaccines.

PMID- 22659490
TI  - Development of fetal and placental innate immune responses during establishment
      of persistent infection with bovine viral diarrhea virus.
AB  - Transplacental viral infections are dependent upon complex interactions between
      feto-placental and maternal immune responses and the stage of fetal development
      at which the infection occurs. Bovine viral diarrhea virus (BVDV) has the ability
      to cross the placenta and infect the fetus. Infection early in gestation with non
      cytopathic (ncp) BVDV leads to persistent infection. Establishment of fetal
      persistent infection results in life-long viremia, virus-specific
      immunotolerance, and may have detrimental developmental consequences. We have
      previously shown that heifers infected experimentally with ncp BVDV type 2 on d.
      75 of gestation had transient robust up-regulation of the type I interferon (IFN)
      stimulated genes (ISGs) 3-15 days after viral inoculation. Blood from
      persistently infected (PI) fetuses, collected 115 days post maternal infection,
      demonstrated moderate chronic up-regulation of ISGs. This infection model was
      used to delineate timing of the development of innate immune responses in the
      fetus and placenta during establishment of persistent infection. It was
      hypothesized that: (i) chronic stimulation of innate immune responses occurs
      following infection of the fetus and (ii) placental production of the type I IFN
      contributes to up-regulation of ISGs in PI fetuses. PI fetuses, generated by
      intranasal inoculation of pregnant heifers with ncp BVDV, and control fetuses
      from uninfected heifers, were collected via Cesarean sections on d. 82, 89, 97,
      192, and 245 of gestation. Fetal viremia was confirmed starting on d. 89.
      Significant up-regulation of mRNA encoding cytosolic dsRNA sensors -RIG-I and
      MDA5 - was detected on d. 82-192. Detection of viral dsRNA by cytosolic sensors
      leads to the stimulation of ISGs, which was reflected in significant up
      regulation of ISG15 mRNA in fetal blood on d. 89, 97, and 192. No difference in
      IFN-alpha and IFN-beta mRNA concentration was found in fetal blood or caruncular
      tissue, while a significant increase in both IFN-alpha and IFN-beta mRNA was seen
      in cotyledons from PI fetuses on d. 192. It is concluded that fetuses respond to
      early gestational ncp BVDV infection by induction of the type I IFN pathway,
      resulting in chronic up-regulation of ISGs. Cotyledonary tissue contributes to up
      regulation of ISGs by increased production of IFNs. The innate immune response
      might partially curtail viral replication in PI fetuses, but is not able to
      eliminate the virus in the absence of a virus-specific adaptive immune response.

PMID- 22659492
TI  - Inhibitory effect of botulinum toxin type A on the NANC system in rat respiratory
      models of neurogenic inflammation.
AB  - This study investigated whether botulinum toxin type A (BTX-A) inhibits
      respiratory neurogenic inflammation in the non-adrenergic, non-cholinergic (NANC)
      transmitter system in rats. Neurogenic inflammation models were induced in
      Sprague Dawley (SD) rats through bilateral cerebral artery occlusion (BCAO) for
      different times (0, 30 and 60 min) or by stimulation with capsaicin at different
      doses (5 or 15 g/kg). Pre-Botzinger Complex-Spikes and the expression of
      substance P, synaptosomal-associated protein-25 (SNAP-25), and reactive oxygen
      species (ROS) were detected with or without pretreatment of rats with BTX-A (15
      or 30 U/kg). BCAO reduced pre-Bot C spike activity (spike/s) and increased the
      breath rate (breaths/s) in an unstable pattern in comparison to controls, while
      pretreatment with BTX-A slightly reduced this phenomenon. Pretreatment with BTX-A
      inhibited BCAO- or capsaicin-induced increases in expression of SNAP-25,
      substance P, and ROS in a dose-dependent manner in brainstem and lung tissue. BTX
      A exerts a suppressive effect on neurogenic inflammation via non-adrenergic, non
      cholinergic transmitters. These results add to the body of evidence elucidating
      the non-cholinergic effects of BTX-A in the context of neurogenic inflammation.

PMID- 22659491
TI  - Characterization of heterotrimeric nucleotide-depleted Galpha(i)-proteins by
      Bodipy-FL-GTPgammaS fluorescence anisotropy.
AB  - Recombinant heterotrimeric G-protein alpha(i1), alpha(i2) and alpha(i3) subunits
      were purified in GDP-depleting conditions by affinity chromatography using
      StrepII-tagged beta1gamma2 subunits. Real-time monitoring of fluorescence
      anisotropy of Bodipy-FL-GTPgammaS was used for characterization of nucleotide
      binding properties and inactivation of the purified proteins. All GDP-depleted
      alpha(i) were unstable at room temperature and therefore nucleotide binding could
      be characterized only in a nonequilibrium state. In comparison to Mg2+, Mn2+
      inhibited nucleotide binding to all alpha(i)-heterotrimers studied and
      accelerated nucleotide release. Mn2+ had stabilizing effect on the nucleotide
      free state of the alpha(i1) subunit, whereas both Mn2+ as well as G-protein
      activation by mastoparan destabilized the alpha(i2) subunit.

PMID- 22659493
TI  - Font effects of Chinese characters and pseudo-characters on the N400: evidence
      for an orthographic processing view.
AB  - Event-related brain potentials (ERPs) were recorded during a Chinese character
      decision task to examine whether N400 amplitude is modulated by stimulus font.
      Results revealed large negative-going ERPs in an N400 time window of 300-500ms to
      stimuli presented in degraded Xing Kai Ti (XKT) font compared with more intact
      Song Ti (ST) font regardless of whether the stimuli were real or pseudo
      characters. ERPs for the pseudo-characters were more negative than for the real
      characters with similar timing and scalp distribution. The N400-like font effect
      on amplitude is interpreted as analogous to an N400 stimulus degradation effect,
      an extension to Holcomb (1993); the degraded perceptual cues provided by XKT
      supposedly account for this degradation effect. This effect is further
      interpreted to reflect relative difficulty, which results from orthographic
      processing difficulty, in retrieving the meaning of XKT stimuli compared with ST
      stimuli.

PMID- 22659494
TI  - A faster immunofluorescence assay for tracking infection progress of human
      cytomegalovirus.
AB  - Immunofluorescence assay (IFA) is one of the most frequently used methods in the
      biological sciences and clinic diagnosis, but it is expensive and time-consuming.
      To overcome these limitations, we developed a faster and more cost-effective IFA
      (f-IFA) by modifying the standard IFA, and applied this method to track the
      progression of human cytomegalovirus (HCMV) infection in different cells. The f
      IFA that we developed not only saves time, but also dramatically reduces the
      quantity of antibody (Ab), which will facilitate the application of IFA in clinic
      diagnosis. f-IFA requires only 15 min for blocking, 10 min incubation for each
      primary and secondary Abs, followed by 1 min extensive wash after each
      incubation. Only 25 MUl of diluted Ab solution was needed for each coverslip at
      the primary and secondary Ab incubation steps. In addition, all steps were
      performed at room temperature. This f-IFA has been applied successfully to follow
      virion entry (pp65) and expression of viral genes (IE1, UL44, and pp65) in order
      to track the details of HCMV infection process. We found that ~0.5% HCMV-infected
      T98G cells formed multiple-micronuclei (IE1 and nucleus staining) and had virus
      shedding (pp65 staining) by f-IFA, which could not be detected by the traditional
      IFA. Our results indicated that f-IFA is a sensitive, convenient, fast, and cost
      effective method for investigating the details of virus infection progress,
      especially HCMV infection. The faster and cost-effective feature with higher
      sensitivity and specificity implies that f-IFA has potential applications in
      clinical diagnosis.

PMID- 22659495
TI  - Effectiveness and limitations of resolving HLA class I and class II by
      heterozygous ambiguity resolving primers (HARPs)--a modified technique of
      sequence-based typing (SBT).
AB  - OBJECTIVES: The aim was to evaluate the use of combination of SBT (sequence based
      typing) and HARP (heterozygous ambiguity resolving primer) in HLA typing to
      acquire high resolution typing results. DESIGN AND METHODS: 167 DNA samples were
      analyzed by SBT. The web site HARPs Finder provided by Conexio Genomics, the
      developer of HARPs (http://www.harpsfinder.conexio-genomics.com/index.html) was
      then used to search for appropriate HARPs. RESULTS: HARPs can resolve 95% of
      ambiguities for locus A; 86% for B and 60% for DRB1 locus. However, there are
      still limitations. Practically PCR products of un-separated alleles are used as
      templates for sequencing by HARP; sometimes, it is still impossible to get
      unambiguous typing. CONCLUSIONS: We outlined the advantages and disadvantages of
      SBT/HARP. A list of HARPs for choice to resolve ambiguity of SBT in Taiwanese
      population is concluded.

PMID- 22659497
TI  - Immunoreactivity of the amino-terminal portion of the amyloid-beta precursor
      protein in the nucleolus.
AB  - The functioning and metabolic pathway of the amyloid beta-precursor protein (APP)
      have not been fully elucidated. To fill this research gap, this study
      immunocytochemically investigated the intracellular localization of APP in the
      neuroblastoma cell line SK-N-SH and in normal primary cells. Using antibodies
      against the amino-terminal portion of the APP molecule, immunoreactivity was
      detected not only in the cytoplasm but also in the nucleus and nucleolus. Further
      analysis revealed the co-localization of amino acids 44-63 of the APP molecule
      with fibrillarin, a nucleolus marker. These findings indicate that a fraction of
      APP, including its amino-terminal portion, may be localized in the nucleus as
      well as in the nucleolus, suggesting an important role of APP in RNA metabolism
      and other intra-nucleolus functions.

PMID- 22659498
TI  - Chrysotoxine, a novel bibenzyl compound selectively antagonizes MPP+, but not
      rotenone, neurotoxicity in dopaminergic SH-SY5Y cells.
AB  - Chrysotoxine is a naturally occurring bibenzyl compound found in medicinal
      Dendrobium species. We previously reported that chrysotoxine structure
      specifically suppressed 6-hydroxydopamine (6-OHDA)-induced dopaminergic cell
      death. Whether chrysotoxine and other structurally similar bibenzyl compounds
      could also inhibit the neurotoxicity of 1-methyl-4-phenyl pyridinium (MPP(+)) and
      rotenone has not been investigated. We showed herein that chrysotoxine inhibited
      MPP(+), but not rotenone, induced dopaminergic cell death in SH-SY5Y cells. The
      overproduction of reactive oxygen species (ROS), mitochondrial dysfunction as
      indexed by the decrease in membrane potential, increase in calcium concentration
      and NF-kappaB activation triggered by MPP(+) were blocked by chrysotoxine
      pretreatment. The imbalance between the pro-apoptotic signals (Bax, caspase-3,
      ERK and p38 MAPK) and the pro-survival signals (Akt/PI3K/GSK-3beta) induced by
      MPP(+) was partially or totally rectified by chrysotoxine. The results indicated
      that ROS inhibition, mitochondria protection, NF-kappaB modulation and regulation
      of multiple signals determining cell survival and cell death were involved in the
      protective effects of chrysotoxine against MPP(+) toxicity in SH-SY5Y cells.
      Given the different toxic profiles of 6-OHDA and MPP(+) as compared to rotenone,
      our results also indicated that DAT inhibition may partially account for the
      neuroprotective effects of chrysotoxine.

PMID- 22659496
TI  - The YAP and TAZ transcription co-activators: key downstream effectors of the
      mammalian Hippo pathway.
AB  - The Hippo signaling pathway was initially defined by genetic studies in
      Drosophila to regulate tissue growth and organ size [1,2]. This pathway is highly
      conserved in mammals and dysregulation of the Hippo pathway has been implicated
      in human cancer. Although the exact extracellular signal that controls the Hippo
      pathway is currently unknown, compelling evidence supports a critical role of the
      Hippo pathway in cell contact inhibition, which is a property commonly lost in
      cancer cells. Many molecules, such as the merlin tumor suppressor protein, have
      been identified as regulating the activity of the core Hippo pathway components
      [1,2]. Acting downstream are two key transcription co-activators, YAP and TAZ,
      which mediate the major gene regulation and biological functions of the Hippo
      pathway. This article will focus on the physiological function and molecular
      regulation of YAP/TAZ and its Drosophila homolog Yki.

PMID- 22659499
TI  - Natronoarchaeum philippinense sp. nov., a haloarchaeon isolated from commercial
      solar salt.
AB  - A Gram-staining-negative, pleomorphic, aerobic, halophilic archaeon, designated
      strain 294-194-5(T), was isolated in Japan from commercial solar salt imported
      from the Philippines. Colonies of strain 294-194-5(T) were translucent and red.
      Strain 294-194-5(T) was able to grow at 20-50  degrees C (optimum, 37-45  degrees
      C), with 14-30 % (w/v) NaCl (optimum, 18 %), and at pH 6.5-8.5 (optimum, pH 8.0).
      MgCl2 was not required for growth. Phylogenetic analysis based on 16S rRNA gene
      sequence similarities showed that strain 294-194-5(T) was most closely related to
      Natronoarchaeum mannanilyticum YSM-123(T) (96.8-97.1 % sequence similarities).
      The major polar lipids of the novel strain were the C20C20 and C20C25 derivatives
      of phosphatidylglycerol and phosphatidylglycerol phosphate methyl ester and the
      same glycolipids (disulfated diglycosyl diether and one unidentified glycolipid)
      as detected in N. mannanilyticum YSM-123(T). The DNA G+C content of strain 294
      194-5(T) was 63.0 mol%. The DNA-DNA relatedness values between the novel strain
      and N. mannanilyticum YSM-123(T)were 46.5 % and 48.5 % (reciprocal). Based on
      these data, strain 294-194-5(T) represents a novel species of the genus
      Natronoarchaeum, for which the name Natronoarchaeum philippinense sp. nov. is
      proposed. The type strain is 294-194-5(T) ( = JCM 16593(T) = CECT 7630(T)).

PMID- 22659500
TI  - Jeongeupia chitinilytica sp. nov., a chitinolytic bacterium isolated from soil.
AB  - A novel bacterium, designated strain Jchi(T), was isolated from soil in Taiwan
      and characterized using a polyphasic approach. Cells of strain Jchi(T) were
      aerobic, Gram-stain-negative, motile and rod-shaped. They contained poly-beta
      hydroxybutyrate granules and formed dark-yellow colonies. Growth occurred at 20
      37  degrees C (optimum between 25 and 30  degrees C), at pH 6.0-8.0 (optimum
      between pH 7.0 and pH 8.0) and with 0-2 % NaCl (optimum between 0 and 1 %).
      Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain
      Jchi(T) belonged to the genus Jeongeupia and that its closest neighbour was
      Jeongeupia naejangsanensis BIO-TAS4-2(T) (98.0 % sequence similarity). The major
      fatty acids (>10 %) of strain Jchi(T) were summed feature 3 (comprising C16 :
      1omega7c and/or C16 : 1omega6c), C16 : 0 and C18 : 1omega7c. The major cellular
      hydroxy fatty acid was C12 : 0 3-OH. The isoprenoid quinone was Q-8 and the
      genomic DNA G+C content was 66.1 mol%. The polar lipid profile consisted of a
      mixture of phosphatidylethanolamine, phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylserine and two unidentified phospholipids.
      The DNA-DNA relatedness value between strain Jchi(T) and J. naejangsanensis BIO
      TAS4-2(T) was about 41.0 %. On the basis of the genotypic and phenotypic data,
      strain Jchi(T) represents a novel species in the genus Jeongeupia, for which the
      name Jeongeupia chitinilytica sp. nov. is proposed. The type strain is Jchi(T) (
      = BCRC 80367(T)  = KCTC 23701(T)).

PMID- 22659501
TI  - Lutibacter flavus sp. nov., a marine bacterium isolated from a tidal flat
      sediment.
AB  - A carotenoid-containing chemoheterotrophic bacterium, designated IMCC1507(T), was
      isolated from a tidal flat sediment of the Yellow Sea, Korea. Strain IMCC1507(T)
      was Gram-negative, yellow, obligately aerobic, non-motile and flexirubin
      negative. 16S rRNA gene sequence analysis indicated that strain IMCC1507(T)
      belonged to the genus Lutibacter in the family Flavobacteriaceae and exhibited
      96.1-97.3 % 16S rRNA sequence similarity with the type strains of described
      species of the genus Lutibacter. DNA-DNA relatedness between strain IMCC1507(T)
      and Lutibacter litoralis KCCM 42118(T) ranged from 3.5+/-2.2 % to 11.2+/-2.4 %,
      indicating that strain IMCC1507(T) represented a novel genomic species in the
      genus Lutibacter. Chemotaxonomic characteristics of the isolate, i.e. the DNA G+C
      content (31.4 mol%), iso-C15 : 0 3-OH, iso-C15 : 0, iso-C15 : 1 G and anteiso-C15
      : 0 as the major fatty acids, MK-6 as the predominant menaquinone and
      phosphatidylethanolamine as the major polar lipid, were consistent with its
      assignment to the genus Lutibacter. However, several phenotypic characteristics,
      including hydrolysis of macromolecules, enzyme activities and carbon source
      oxidation, differentiated strain IMCC1507(T) from members of the genus. Data from
      this study indicate that strain IMCC1507(T) represents a novel species in the
      genus Lutibacter, for which the name Lutibacter flavus sp. nov. is proposed. The
      type strain is IMCC1507(T) ( = KACC 14312(T)  = NBRC 107589(T)).

PMID- 22659502
TI  - Gallaecimonas xiamenensis sp. nov., isolated from seawater.
AB  - A taxonomic study was carried out on a novel bacterium, designated strain 3-C
      1(T), which was isolated from a crude-oil-degrading consortium produced by
      enrichment of a sample of surface seawater collected near Xiamen Island in China.
      Cells of the novel strain were Gram-reaction-negative, oxidase- and catalase
      positive, rod-shaped, motile and amphitrichous. Growth was observed with 0-12 %
      (w/v) NaCl and at temperatures of 10-42  degrees C. The novel strain was
      incapable of nitrate reduction. Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that strain 3-C-1(T) belonged to the genus Gallaecimonas and
      was most closely related to Gallaecimonas pentaromativorans CEE_131(T) (with
      sequence similarities of 96.5-96.8 %). The gyrB gene sequence of strain 3-C-1(T)
      was also similar to that of G. pentaromativorans CEE_131(T) (89.4 % sequence
      similarity). The results of PCR-based comparison of repetitive extragenic
      palindromic elements (Rep-PCR fingerprinting) allowed strain 3-C-1(T) to be
      distinguished from G. pentaromativorans CEE_131(T). The principal fatty acids of
      the novel strain were C16 : 0, C12 : 0 3-OH, summed feature 3 (C16 : 1omega6c
      and/or C16 : 1omega7c) and summed feature 8 (C18 : 1omega6c and/or C18 :
      1omega7c). The G+C content of the novel strain's genomic DNA was 61.3 mol%. The
      combined genotypic and phenotypic data indicate that strain 3-C-1(T) represents a
      novel species of the genus Gallaecimonas, for which the name Gallaecimonas
      xiamenensis sp. nov. is proposed. The type strain is 3-C-1(T) ( = CCTCC AB
      209060(T)  = LMG 25226(T)  = MCCC 1A01354(T)).

PMID- 22659504
TI  - Luteivirga sdotyamensis gen. nov., sp. nov., a novel bacterium of the phylum
      Bacteroidetes isolated from the Mediterranean sponge Axinella polypoides.
AB  - A novel aerobic bacterium, designated strain PIII.02(T), was isolated from a
      Mediterranean sponge (Axinella polypoides) collected off the Israeli coast near
      Sdot Yam. The non-motile cells were Gram-staining-negative, oxidase-positive and
      catalase-positive. The orange pigment of colonies growing on marine agar was
      neither diffusible nor flexirubin-like. Strain PIII.02(T) grew at 15-35  degrees
      C, at pH 6.0-9.0, with 2.0-7.0 % (w/v) NaCl, and with 1.0-8.0 % (w/v) sea salts.
      The predominant fatty acids were iso-C15 : 0, iso-C16 : 1 H, iso-C16 : 0, C16 :
      0, anteiso-C15 : 0 and C16 : 1omega7c. The major respiratory quinone was MK-7.
      The genomic DNA G+C content of the novel strain was 38.1 mol%. Results from 16S
      rRNA gene sequence analysis indicated that strain PIII.02(T) was distantly
      related to established members of the phylum Bacteroidetes. The established
      species found to be most closely related to the novel strain was Persicobacter
      diffluens NCIMB 1402(T) (87.6 % 16S rRNA gene sequence similarity). Based on the
      phenotypic and chemotaxonomic data and the results of the phylogenetic analyses,
      strain PIII.02(T) represents a novel species of a new genus, for which the name
      Luteivirga sdotyamensis gen. nov., sp. nov. is proposed. The type strain is
      PIII.02(T) ( = ATCC BAA-2393(T)  = LMG 26723(T)).

PMID- 22659503
TI  - Fontibacter ferrireducens sp. nov., an Fe(III)-reducing bacterium isolated from a
      microbial fuel cell.
AB  - A novel, dissimilatory Fe(III)-reducing bacterium, designated strain SgZ-2(T),
      which could couple glucose oxidation to iron reduction for energy conservation,
      was isolated from a microbial fuel cell. The isolate was Gram-staining-negative,
      catalase-positive, oxidase-negative and facultatively anaerobic. The strain was
      able to grow on tryptic soy agar at 15-37  degrees C and in the presence of 0-5 %
      (w/v) NaCl. The predominant cellular fatty acids (>5 %) were iso-C15 : 0, iso-C17
      : 0 3-OH and iso-C17 : 1omega9c; the major respiratory quinone was MK-7; the
      major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and
      three other unidentified lipids; and the DNA G+C content was 55.3 mol%.
      Phylogenetic analyses based on 16S rRNA sequences showed that the novel strain
      was most closely related to Fontibacter flavus CC-GZM-130(T) (99.9 % sequence
      similarity), and was a member of the family Cyclobacteriaceae. The levels of DNA
      DNA relatedness observed between strain SgZ-2(T) and F. flavus CCM 7650(T) (<41
      %) indicated that the two strains represented two distinct species. Based on
      phylogenetic analyses and phenotypic characteristics, strain SgZ-2(T) represents
      a novel species of the genus Fontibacter, for which the name Fontibacter
      ferrireducens sp. nov. is proposed. The type strain is SgZ-2(T) ( = CCTCC M
      2011498(T)  = KACC 16525(T)).

PMID- 22659505
TI  - Desulfoconvexum algidum gen. nov., sp. nov., a psychrophilic sulfate-reducing
      bacterium isolated from a permanently cold marine sediment.
AB  - A sulfate-reducing bacterium, designated JHA1(T), was isolated from a permanently
      cold marine sediment sampled in an Artic fjord on the north-west coast of
      Svalbard. The isolate was originally enriched at 4  degrees C in a highly diluted
      liquid culture amended with hydrogen and sulfate. Strain JHA1(T) was a
      psychrophile, growing fastest between 14 and 16  degrees C and not growing above
      20  degrees C. Fastest growth was found at neutral pH (pH 7.2-7.4) and at marine
      concentrations of NaCl (20-30 g l(-1)). Phylogenetic analysis of 16S rRNA gene
      sequences revealed that strain JHA1(T) was a member of the family
      Desulfobacteraceae in the Deltaproteobacteria. The isolate shared 99 % 16S rRNA
      gene sequence similarity with an environmental sequence obtained from permanently
      cold Antarctic sediment. The closest recognized relatives were Desulfobacula
      phenolica DSM 3384(T) and Desulfobacula toluolica DSM 7467(T) (both <95 %
      sequence similarity). In contrast to its closest phylogenetic relatives, strain
      JHA1(T) grew chemolithoautotrophically with hydrogen as an electron donor. CO
      dehydrogenase activity indicated the operation of the reductive acetyl-CoA
      pathway for inorganic carbon assimilation. Beside differences in physiology and
      morphology, strain JHA1(T) could be distinguished chemotaxonomically from the
      genus Desulfobacula by the absence of the cellular fatty acid C16 : 0 10-methyl.
      Phylogenetic differentiation from other genera was further supported by DsrAB and
      AprBA sequence analysis. Based on the described phylogenetic and phenotypic
      differences between strain JHA1(T) and its closest relatives, the establishment
      of a novel genus and a novel species, Desulfoconvexum algidum gen. nov., sp. nov.
      is proposed. The type strain is JHA1(T) ( = DSM 21856(T)  = JCM 16085(T)).

PMID- 22659506
TI  - Derxia lacustris sp. nov., a nitrogen-fixing bacterium isolated from a freshwater
      lake.
AB  - A novel nitrogen-fixing strain, designated HL-12(T), was isolated from a
      freshwater lake in Taiwan. Cells of strain HL-12(T) were aerobic, Gram-negative,
      motile rods that were surrounded by a thick capsule, contained poly-beta
      hydroxybutyrate granules, and formed light-yellow to brownish-red colonies.
      Growth occurred at 15-40  degrees C (optimum 25-35  degrees C), at pH 6.0-7.0
      (optimum pH 6.0) and with 0-4 % NaCl (optimum 0-1 %). Phylogenetic analysis based
      on 16S rRNA gene sequences showed that strain HL-12(T) belonged to the genus
      Derxia and exhibited 99.1 and 98.8 % 16S rRNA gene sequence similarity,
      respectively, with Derxia gummosa IAM 14990 and D. gummosa IAM 13946(T). The
      major fatty acids (>10 %) of strain HL-12(T) were summed feature 3 (comprising
      C16 : 1omega7c and/or C16 : 1omega6c), C16 : 0 and C18 : 1omega7c. The cellular
      hydroxy fatty acids were C12 : 0 3-OH, C14 : 0 2-OH and C14 : 0 3-OH. The
      isoprenoid quinone was Q-8 and the DNA G+C content was 72.0 mol%. The polar lipid
      profile contained phosphatidylethanolamine, phosphatidylglycerol,
      diphosphatidylglycerol and several unknown aminophospholipids and phospholipids.
      DNA-DNA relatedness between strain HL-12(T) and http://dx.doi.org/10.1601/nm.1758
      LMG 3975 and http://dx.doi.org/10.1601/nm.1758 LMG 3977(T) was <70 %. On the
      basis of the genotypic and phenotypic data, strain HL-12(T) represents a novel
      species in the genus Derxia, for which the name Derxia lacustris sp. nov. is
      proposed. The type strain is HL-12(T) ( = BCRC 80208(T)  = KCTC 23311(T)).

PMID- 22659507
TI  - Sphingobacterium psychroaquaticum sp. nov., a psychrophilic bacterium isolated
      from Lake Michigan water.
AB  - A psychrophilic, Gram-negative bacterium, designated MOL-1(T), was isolated from
      water of Lake Michigan. 16S rRNA gene sequence analysis revealed that the
      sequence of strain MOL-1(T) has sequence similarity of 95.6, 94.8, 94.3, 94.3,
      94.2 and 93.9 %, respectively, to the 16S rRNA gene sequences of Sphingobacterium
      shayense HS39(T), S. lactis WCC 4512(T), S. composti T5-12(T), S. daejeonense TR6
      04(T), S. bambusae IBFC2009(T) and S. alimentarium WCC 4521(T). The major
      cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (iso
      C15 : 0 2-OH and/or C16 : 1omega7c). Menaquinone MK-7 is the predominant
      respiratory quinone, while sym-homospermidine is the predominant polyamine. The
      polar lipid profile is composed of the predominant lipids
      phosphatidylethanolamine and unidentified polar lipid L2, with moderate amounts
      of unidentified polar lipids L1, L5 and L6 and unidentified aminophospholipids
      APL1 and APL2 and minor to trace amounts of unidentified polar lipids L3, L4, L7,
      L8, L9 and L10, unidentified phospholipid PL4 and unidentified aminophospholipid
      APL3. After molecular and phenotypic studies, including chemotaxonomic analyses,
      it was concluded that strain MOL-1(T) represents a novel Sphingobacterium
      species, for which the name Sphingobacterium psychroaquaticum sp. nov. is
      proposed. The type strain is MOL-1(T) ( = NRRL B-59232(T)  = DSM 22418(T)).

PMID- 22659508
TI  - NecroX-7 prevents oxidative stress-induced cardiomyopathy by inhibition of NADPH
      oxidase activity in rats.
AB  - Oxidative stress is one of the causes of cardiomyopathy. In the present study,
      NecroXs, novel class of mitochondrial ROS/RNS scavengers, were evaluated for
      cardioprotection in in vitro and in vivo model, and the putative mechanism of the
      cardioprotection of NecroX-7 was investigated by global gene expression profiling
      and subsequent biochemical analysis. NecroX-7 prevented tert-butyl hydroperoxide
      (tBHP)-induced death of H9C2 rat cardiomyocytes at EC(50)=0.057 MUM. In
      doxorubicin (DOX)-induced cardiomyopathy in rats, NecroX-7 significantly reduced
      the plasma levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH)
      which were increased by DOX treatment (p<0.05). Microarray analysis revealed that
      21 genes differentially expressed in tBHP-treated H9C2 cells were involved in
      'Production of reactive oxygen species' (p=0.022), and they were resolved by
      concurrent NecroX-7 treatment. Gene-to-gene networking also identified that
      NecroX-7 relieved cell death through Ncf1/p47phox and Rac2 modulation. In
      subsequent biochemical analysis, NecroX-7 inhibited NADPH oxidase (NOX) activity
      by 53.3% (p<0.001). These findings demonstrate that NecroX-7, in part, provides
      substantial protection of cardiomyopathy induced by tBHP or DOX via NOX-mediated
      cell death.

PMID- 22659509
TI  - Novel object recognition ability in female mice following exposure to
      nanoparticle-rich diesel exhaust.
AB  - Recently, our laboratory reported that exposure to nanoparticle-rich diesel
      exhaust (NRDE) for 3 months impaired hippocampus-dependent spatial learning
      ability and up-regulated the expressions of memory function-related genes in the
      hippocampus of female mice. However, whether NRDE affects the hippocampus
      dependent non-spatial learning ability and the mechanism of NRDE-induced
      neurotoxicity was unknown. Female BALB/c mice were exposed to clean air, middle
      dose NRDE (M-NRDE, 47 MUg/m(3)), high-dose NRDE (H-NRDE, 129 MUg/m(3)), or
      filtered H-NRDE (F-DE) for 3 months. We then investigated the effect of NRDE
      exposure on non-spatial learning ability and the expression of genes related to
      glutamate neurotransmission using a novel object recognition test and a real-time
      RT-PCR analysis, respectively. We also examined microglia marker Iba1
      immunoreactivity in the hippocampus using immunohistochemical analyses. Mice
      exposed to H-NRDE or F-DE could not discriminate between familiar and novel
      objects. The control and M-NRDE-exposed groups showed a significantly increased
      discrimination index, compared to the H-NRDE-exposed group. Although no
      significant changes in the expression levels of the NMDA receptor subunits were
      observed, the expression of glutamate transporter EAAT4 was decreased and that of
      glutamic acid decarboxylase GAD65 was increased in the hippocampus of H-NRDE
      exposed mice, compared with the expression levels in control mice. We also found
      that microglia activation was prominent in the hippocampal area of the H-NRDE
      exposed mice, compared with the other groups. These results indicated that
      exposure to NRDE for 3 months impaired the novel object recognition ability. The
      present study suggests that genes related to glutamate metabolism may be involved
      in the NRDE-induced neurotoxicity observed in the present mouse model.

PMID- 22659510
TI  - Disruptive cell cycle regulation involving epigenetic downregulation of Cdkn2a
      (p16(Ink4a)) in early-stage liver tumor-promotion facilitating liver cell
      regeneration in rats.
AB  - Cell cycle aberration was immunohistochemically examined in relation to
      preneoplastic liver cell foci expressing glutathione S-transferase placental form
      (GST-P) at early stages of tumor-promotion in rats with thioacetamide (TAA), a
      hepatocarcinogen facilitating liver cell regeneration. Immunoexpression of
      p16(Ink4a) following exposure to other hepatocarcinogens/promoters and its DNA
      methylation status were also analyzed during early and late tumor-promotion
      stages. GST-P(+) liver cell foci increased cell proliferation and decreased
      apoptosis when compared with surrounding liver cells. In concordance with GST
      P(+) foci, checkpoint proteins at G(1)/S (p21(Cip1), p27(Kip1) and p16(Ink4a))
      and G(2)/M (phospho-checkpoint kinase 1, Cdc25c and phospho-Wee1) were either up-
      or downregulated. Cellular distribution within GST-P(+) foci was either increased
      or decreased with proteins related to G(2)-M phase or DNA damage (topoisomerase
      IIalpha, phospho-histone H2AX, phospho-histone H3 and Cdc2). In particular,
      p16(Ink4a) typically downregulated in GST-P(+) foci and regenerative nodules at
      early tumor-promotion stage with hepatocarcinogens facilitating liver cell
      regeneration and in neoplastic lesions at late tumor-promotion stage with
      hepatocarcinogens/promoters irrespective of regenerating potential.
      Hypermethylation at exon 2 of Cdkn2a was detected at both early- and late-stages.
      Thus, diverse disruptive expression of G(1)/S and G(2)/M proteins, which allows
      for clonal selection of GST-P(+) foci, results in the acquisition of multiple
      aberrant phenotypes to disrupt checkpoint function. Moreover, increased DNA
      damage responses within GST-P(+) foci may be the signature of genetic
      alterations. Intraexonic hypermethylation may be responsible for p16(Ink4a)
      downregulation, which facilitates cell cycle progression in early preneoplastic
      lesions produced by repeated cell regeneration and late-stage neoplastic lesions
      irrespective of the carcinogenic mechanism.

PMID- 22659511
TI  - Simultaneously recorded single-exhalation profiles of ethanol, water vapour and
      CO(2) in humans: impact of pharmacokinetic phases on ethanol airway exchange.
AB  - The breath alcohol concentration (BrAC) standardized to the alveolar water vapour
      concentration has been shown to closely predict the arterial blood alcohol
      (ethanol) concentration (ABAC). However, a transient increase in the ABAC/BrAC
      ratio has been noted, when alcohol is absorbed from the gastrointestinal tract
      (absorption phase) and the ABAC rapidly rises. We analysed the plot of
      simultaneously recorded alcohol, water vapour and CO(2) against exhaled volume
      (volumetric expirogram) for respiratory dead space volume (VD), cumulative gas
      output and phase III slope within one breath to evaluate whether changes in the
      BrAC profile could explain this variability. Eight healthy subjects performed
      exhalations through pre-heated non-restrictive mouthpieces and the concentrations
      were measured by infrared absorption. In the absorption phase, the respiratory VD
      of alcohol was transiently increased and the exhaled alcohol was displaced to the
      latter part of the expirogram. In the post-absorption phase, the respiratory VD
      for alcohol and water vapour was stable and always less than the respiratory VD
      for CO(2), indicating that the first part of the exhaled alcohol and water
      originated from the conducting airway. The position of the BrAC profile between
      water vapour and CO(2) in the post-absorptive phase indicates an interaction
      within the conducting airway, probably including a deposition of alcohol onto the
      mucosa during exhalation. We conclude that the increase in the ABAC/BrAC ratio
      during the absorption phase of alcohol coincides with a transient increase in
      respiratory VD of alcohol and a delay in the appearance of alcohol in the exhaled
      air as the exhalation proceeds compared with the post-absorption phase.

PMID- 22659513
TI  - Genetic divergence, speciation and biogeography of Mustelus (sharks) in the
      central Indo-Pacific and Australasia.
AB  - The shark genus Mustelus is speciose, commercially important and systematically
      troublesome. We use a molecular approach combining inter and intra-specific data
      to investigate Mustelus species in the central Indo-Pacific and Australasia. Our
      analysis supports two Mustelus clades, one comprising species with no white spots
      and a placental reproductive mode and a second clade of white spotted, aplacental
      species. Levels of genetic divergence are low, especially among species in the
      white spotted, aplacental clade and this should be taken into account when
      employing molecular data to delineate species. Our data support the hypothesis of
      a radiation following dispersal from a northern hemisphere ancestor. Molecular
      dating suggests that localised speciation in Australasia may have occurred during
      the Pleistocene. We propose that some of the difficulties associated with
      Mustelus systematics relate to a recent radiation, particularly in the
      Australasian region.

PMID- 22659512
TI  - Rapid range expansion in the Great Plains narrow-mouthed toad (Gastrophryne
      olivacea) and a revised taxonomy for North American microhylids.
AB  - We investigated genetic variation within the Great Plains narrow-mouthed toad,
      Gastrophryne olivacea, across its geographic range in the United States and
      Mexico. An analysis of mitochondrial DNA (mtDNA) from 105 frogs revealed
      remarkably low levels of genetic diversity in individuals inhabiting the central
      United States and northern Mexico. We found that this widespread matrilineal
      lineage is divergent (ca. 2% in mtDNA) from haplotypes that originate from the
      western United States and western coast of Mexico. Using a dataset that included
      all five species of Gastrophryne and both species of the closely related genus
      Hypopachus, we investigated the phylogenetic placement of G. olivacea. This
      analysis recovered strong support that G. olivacea, the tropically distributed G.
      elegans, and the temperately distributed G. carolinensis constitute a
      monophyletic assemblage. However, the placement of G. pictiventris and G. usta
      render Gastrophryne paraphyletic with respect to Hypopachus. To complement our
      mitochondrial analysis, we examined a small fragment of nuclear DNA and recovered
      consistent patterns. In light of our findings we recommend (1) the resurrection
      of the nomen G. mazatlanensisTaylor (1943) for the disjunct western clade of G.
      olivacea and (2) the tentative placement of G. pictiventris and G. usta in
      Hypopachus. To explore possible scenarios leading to low levels of genetic
      diversity in G. olivacea, we used mismatch distributions and Bayesian Skyline
      plots to examine historic population expansion and demography. Collectively these
      analyses suggest that G. olivacea rapidly expanded in effective population size
      and geographic range during the late Pleistocene or early Holocene. This
      hypothesis is consistent with fossil data from northern localities and
      contemporary observations that suggest ongoing northern expansion. Given our
      findings, we suspect that the rapid range expansion of G. olivacea may have been
      facilitated by ecological associations with open habitats and seasonal water
      bodies.

PMID- 22659514
TI  - Phylogenetic analysis of four nuclear protein-encoding genes largely corroborates
      the traditional classification of Bivalvia (Mollusca).
AB  - Revived interest in molluscan phylogeny has resulted in a torrent of molecular
      sequence data from phylogenetic, mitogenomic, and phylogenomic studies. Despite
      recent progress, basal relationships of the class Bivalvia remain contentious,
      owing to conflicting morphological and molecular hypotheses. Marked incongruity
      of phylogenetic signal in datasets heavily represented by nuclear ribosomal genes
      versus mitochondrial genes has also impeded consensus on the type of molecular
      data best suited for investigating bivalve relationships. To arbitrate
      conflicting phylogenetic hypotheses, we evaluated the utility of four nuclear
      protein-encoding genes-ATP synthase beta, elongation factor-1alpha, myosin heavy
      chain type II, and RNA polymerase II-for resolving the basal relationships of
      Bivalvia. We sampled all five major lineages of bivalves (Archiheterodonta,
      Euheterodonta [including Anomalodesmata], Palaeoheterodonta, Protobranchia, and
      Pteriomorphia) and inferred relationships using maximum likelihood and Bayesian
      approaches. To investigate the robustness of the phylogenetic signal embedded in
      the data, we implemented additional datasets wherein length variability and/or
      third codon positions were eliminated. Results obtained include (a) the clade
      (Nuculanida+Opponobranchia), i.e., the traditionally defined Protobranchia; (b)
      the monophyly of Pteriomorphia; (c) the clade
      (Archiheterodonta+Palaeoheterodonta); (d) the monophyly of the traditionally
      defined Euheterodonta (including Anomalodesmata); and (e) the monophyly of
      Heteroconchia, i.e., (Palaeoheterodonta+Archiheterodonta+Euheterodonta). The
      stability of the basal tree topology to dataset manipulation is indicative of
      signal robustness in these four genes. The inferred tree topology corresponds
      closely to those obtained by datasets dominated by nuclear ribosomal genes (18S
      rRNA and 28S rRNA), controverting recent taxonomic actions based solely upon
      mitochondrial gene phylogenies.

PMID- 22659515
TI  - The influence of riverine barriers on phylogeographic patterns of Malagasy reed
      frogs (Heterixalus).
AB  - We analyzed the influence of large rivers on the phylogeography of endemic
      widespread amphibians along Madagascar's east coast, using as models various
      species and species complexes of Malagasy reed frogs (Heterixalus spp.) that are
      specialized to either highland or lowland habitats. We assembled a dense sampling
      across the full species ranges and used mitochondrial (cob) as well as nuclear
      (Rag-1) DNA sequences to assess their phylogeographies. A multigene mtDNA
      phylogeny of each species was constructed to establish the relationships among
      the main phylogroups, in order to understand the geographical regions of clade
      origins and possible directions of historical range expansions. Distinct
      intraspecific lineages as diagnosed by mitochondrial haplotype clades were found
      in highlands and lowlands. Most geographical boundaries among these phylogroups
      did not coincide with rivers, indicating that the influence of rivers on the
      primary divergence of phylogroups is probably minor in these frogs. Nevertheless,
      we found evidence for the influence of one riverine barrier in the lowland
      species complex, where the most important genetic discontinuity (the border
      between Heterixalus madagascariensis and H. alboguttatus) coincides with the
      geographical position of the Mangoro River on Madagascar's central east coast.
      Analyses of the highland species H. betsileo revealed the existence of six deep
      haplotype lineages, separated in two major subpopulations which differ largely in
      altitudinal distribution and do not overlap with the geographical settings of
      rivers in the highlands. Furthermore, our analyses indicated that most of the
      major intraspecific lineages of reed frogs show signs of a rather recent
      population expansion.

PMID- 22659516
TI  - A dated phylogeny of the papaya family (Caricaceae) reveals the crop's closest
      relatives and the family's biogeographic history.
AB  - Papaya (Carica papaya) is a crop of great economic importance, and the species
      was among the first plants to have its genome sequenced. However, there has never
      been a complete species-level phylogeny for the Caricaceae, and the crop's
      closest relatives are therefore unknown. We investigated the evolution of the
      Caricaceae based on sequences from all species and genera, the monospecific
      Carica, African Cylicomorpha with two species, South American Jacaratia and
      Vasconcellea with together c. 28 species, and Mexican/Guatemalan Jarilla and
      Horovitzia with four species. Most Caricaceae are trees or shrubs; the species of
      Jarilla, however, are herbaceous. We generated a matrix of 4711 nuclear and
      plastid DNA characters and used maximum likelihood (ML) and Bayesian analysis to
      infer species relationships, rooting trees on the Moringaceae. Divergence times
      were estimated under relaxed and strict molecular clocks, using different subsets
      of the data. Ancestral area reconstruction relied on a ML approach. The deepest
      split in the Caricaceae occurred during the Late Eocene, when the ancestor of the
      Neotropical clade arrived from Africa. In South America, major diversification
      events coincide with the Miocene northern Andean uplift and the initial phase of
      the tectonic collision between South America and Panama resulting in the
      Panamanian land bridge. Carica papaya is sister to Jarilla/Horovitzia, and all
      three diverged from South American Caricaceae in the Oligocene, 27 (22-33) Ma
      ago, coincident with the early stages of the formation of the Panamanian Isthmus.
      The discovery that C. papaya is closest to a clade of herbaceous or thin-stemmed
      species has implications for plant breeders who have so far tried to cross papaya
      only with woody highland papayas (Vasconcellea).

PMID- 22659517
TI  - A multi-locus phylogeny reveals a complex pattern of diversification related to
      climate and habitat heterogeneity in southern African white-eyes.
AB  - The recent, rapid radiation of Zosteropidae, coupled with their high levels of
      colonizing ability and phenotypic diversity, makes species delimitation within
      this family problematic. Given these problems, challenges to establish the
      mechanisms driving diversity and speciation within this group have arisen. Four
      morphologically distinct southern African Zosterops taxa, with a contentious
      taxonomic past, provide such a challenge. Here, supplemented with morphological
      and environmental analytical techniques, a combination of mitochondrial and
      nuclear markers were analyzed using Bayesian and Likelihood methods to determine
      their speciation patterns and to establish the phylogenetic relationships of
      these four morphologically diverse southern African Zosterops taxa. Nearly all
      individuals were phenotypically diagnosable, even those individuals collected in
      areas of contact between taxa. Localities where two or more taxa co-occur appear
      to possess intermediate environmental characteristics. Initial Bayesian and
      Likelihood mitochondrial DNA analyses and Bayesian structure analyses of the
      combined nuclear markers indicated levels of hybridization in areas of sympatry.
      A combined mtDNA and nuclear DNA analysis and a species tree analysis (with
      hybrids excluded) placed Z. pallidus as sister to the other southern African
      taxa, with Z. senegalensis the putative sister taxon to a clade comprising Z.
      capensis and Z. virens. The grouping of taxon-specific sampling localities and
      the apparent intermediate nature of birds from areas of sympatry points toward an
      influence of habitat type and the associated climatic conditions in driving
      Zosterops diversification in southern Africa.

PMID- 22659518
TI  - Long-term continuous entecavir therapy in nucleos(t)ide-naive chronic hepatitis B
      patients.
AB  - BACKGROUND & AIMS: We determined the antiviral potency and viral resistance rate
      after 4 years of continuous entecavir treatment in patients with chronic
      hepatitis B (CHB) infection. METHODS: The cumulative rates of undetectable
      hepatitis B virus DNA (HBV DNA;<2.6 log(10) copies/ml), hepatitis B e antigen
      (HBeAg) seronegativity, seroconversion, alanine aminotransferase (ALT)
      normalization, and entecavir signature mutations were calculated in 474
      nucleos(t)ide-naive CHB patients (HBeAg-positive: 47%) on continuous entecavir
      treatment for 4 years. RESULTS: Median age was 47 years and follow-up period was
      2.4 years, with 403, 281, 165, and 73 patients followed-up for at least 1, 2, 3,
      and 4 years, respectively. Incremental increases were observed in the rates of
      undetectable HBV DNA, HBeAg seroclearance and seroconversion, and ALT
      normalization, reaching 96%, 42%, 38% and 93%, respectively, by the fourth year.
      In all, 100% and 93% of patients negative and positive for HBeAg, respectively,
      had undetectable HBV DNA at year 4. Of 165 patients, HBV DNA was detectable in
      nine patients after 3 years. Multivariate analysis identified HBV DNA level
      (<=7.6 log(10) copies/ml, OR=15.8; 95% CI=43.1-79.9, P=0.001) as an independent
      predictor of undetectable HBV DNA at year 3. Five patients experienced
      virological breakthrough including two (0.4%) who developed entecavir-resistance
      mutations. CONCLUSIONS: Continuous treatment of nucleos(t)ide-naive CHB patients
      with entecavir over 4 years was associated with 96% chance of undetectable HBV
      DNA and only 0.4% chance of emerging entecavir-resistant mutations.

PMID- 22659519
TI  - S-adenosylmethionine (SAMe) therapy in liver disease: a review of current
      evidence and clinical utility.
AB  - S-adenosyl-L-methionine (SAMe; AdoMet) is an important, metabolically pleiotropic
      molecule that participates in multiple cellular reactions as the precursor for
      the synthesis of glutathione and principle methyl donor required for methylation
      of nucleic acids, phospholipids, histones, biogenic amines, and proteins. SAMe
      synthesis is depressed in chronic liver disease and so there has been
      considerable interest in the utility of SAMe to ameliorate disease severity.
      Despite encouraging pre-clinical data confirming that SAMe depletion can
      exacerbate liver injury and supporting a hepatoprotective role for SAMe therapy,
      to date no large, high-quality randomised clinical trials have been performed
      that establish clinical utility in specific disease states. Here, we offer an in
      depth review of the published scientific literature relating to the physiological
      and pathophysiological roles of SAMe and its therapeutic use in liver disease,
      critically assessing implications for clinical practice and offering
      recommendations for further research.

PMID- 22659520
TI  - Genomics and HCV infection: progression of fibrosis and treatment response.
AB  - HCV infection is a global health problem that affects 170 million people
      worldwide. The severity of the disease varies from asymptomatic chronic infection
      to cirrhosis and hepatocellular carcinoma (HCC). Recently, the standard of care
      for genotype 1 patients has greatly improved with the addition of protease
      inhibitors (telaprevir or boceprevir) to pegylated interferon (PegIFN) and
      ribavirin (RBV). The prediction of fibrosis progression and the response to
      antiviral treatment are two major issues in the management of patients with
      chronic hepatitis C. Differential expression of mRNAs was first analyzed for both
      progression of fibrosis and treatment response. Specific polymorphisms,
      associated with either fibrosis or viral response, were identified thanks to
      major improvements in genome scanning technologies. Since 2009, several
      independent genome wide association studies (GWAS) have reported an association
      between genetic polymorphisms within the IL-28B promoter and both natural and
      treatment-induced clearance in genotype 1 infected patients. These different
      studies showed the strong association and the importance of IL-28B polymorphisms
      in the treatment response. Combining the different genetic factors could improve
      their predictive value and help identify patients at a high risk of progression
      of fibrosis as well as those with a lower chance of responding to treatment. The
      aim of this review was to discuss the genomic factors (mRNAs, miRNAs, and SNPs)
      and HCV infection with clinical implications for either progression of fibrosis
      or treatment response. Recent findings on the IL-28B polymorphism and its
      application in clinical practice will also be discussed.

PMID- 22659521
TI  - Is blood of uncomplicated hemochromatosis patients safe and effective for blood
      transfusion? A systematic review.
AB  - Hemochromatosis is a disorder of the iron metabolism, characterized by high body
      iron content, necessitating frequent phlebotomies to remove excess iron. In some
      countries, this blood is discarded and not used for blood transfusion because of
      the non-voluntary character of this donation, and because a potential risk of
      microbial contamination of the donor blood is assumed. A systematic review was
      performed in order to collect and critically examine solid evidence with regard
      to the effectiveness and safety of blood for transfusion when derived from
      hemochromatosis patients who do not suffer from complications or organ damage.
      Using three databases (The Cochrane Library, MEDLINE, and Embase) we searched for
      studies from date of inception until January 2012. Out of 3470 articles, 80
      references that were relevant to our question were selected, including many
      opinion pieces, comments, letters, and narrative reviews. Based on our selection
      criteria, we finally retained only six observational studies, so evidence on this
      subject is scarce and furthermore, the strength of the available evidence is low
      to very low, due to poor study designs. We found no evidence that red blood cell
      concentrates from hemochromatosis patients without complications of iron overload
      do not comply with the physiological quality requirements for transfusion, nor
      that their blood would present a greater risk to recipient safety than blood from
      non-hemochromatosis donors. However, in vitro findings from two studies suggest
      that iron-overloaded patients would be more susceptible to bacterial growth, but
      future in vivo studies are warranted to confirm this. Based on this, we call for
      harmonization of the blood donor selection policy among countries allowing
      hemochromatosis patients who do not suffer from complications of iron overload to
      donate blood, once iron levels are normalized.

PMID- 22659523
TI  - Conjugated linoleic acid in the maternal diet differentially enhances growth and
      cortical spreading depression in the rat progeny.
AB  - BACKGROUND: Conjugated linoleic acids (CLA) are fatty acids that are found in the
      lipids from goat milk, and appear to protect neurons from excitotoxicity.
      METHODS: We investigated in developing rats the effects of a maternal CLA-rich
      diet (containing 7% lipids from goat milk) on body development and cerebral
      electrical activity of the progeny from dams receiving the CLA diet during
      gestation (G), lactation (L) or both periods (G+L). RESULTS: Compared to a
      control group (C) receiving a diet with 7% soybean oil, body weight increased at
      14, 21 and 28 days, but not at 35-45 days, in L and G+L groups (P<0.05). No
      intergroup difference was found on body and brain weights, body length, abdominal
      and thoracic circumferences, body mass index and abdominal to thoracic
      circumference ratio at 35-45 days. In contrast, at this later age the CSD
      velocities of propagation were significantly higher (P<0.05) in L as compared
      with the C and G group, and in the L+G, as compared with the C, G and L groups,
      suggesting a long-lasting brain effect. CONCLUSION: These data indicate that a
      maternal CLA-rich diet can differentially influence body weight increment (short
      term effect), and CSD propagation (long-term effect) in the progeny, and the
      lactation is the most critical period for such diet actions. GENERAL
      SIGNIFICANCE: The facilitating effect of the lipids from goat milk on an
      excitability-related phenomenon in the brain (CSD) can be of clinical relevance,
      since CSD has been associated to neurological disturbances like migraine and
      epilepsy.

PMID- 22659522
TI  - The U-Box E3 ligase SPL11/PUB13 is a convergence point of defense and flowering
      signaling in plants.

PMID- 22659524
TI  - A plant peptide: N-glycanase orthologue facilitates glycoprotein ER-associated
      degradation in yeast.
AB  - BACKGROUND: The cytoplasmic peptide:N-glycanase (PNGase) is a deglycosylating
      enzyme involved in the ER-associated degradation (ERAD) process, while ERAD
      independent activities are also reported. Previous biochemical analyses indicated
      that the cytoplasmic PNGase orthologue in Arabidopsis thaliana (AtPNG1) can
      function as not only PNGase but also transglutaminase, while its in vivo function
      remained unclarified. METHODS: AtPNG1 was expressed in Saccharomyces cerevisiae
      and its in vivo role on PNGase-dependent ERAD pathway was examined. RESULTS:
      AtPNG1 could facilitate the ERAD through its deglycosylation activity. Moreover,
      a catalytic mutant of AtPNG1 (AtPNG1(C251A)) was found to significantly impair
      the ERAD process. This result was found to be N-glycan-dependent, as the
      AtPNG(C251A) did not affect the stability of the non-glycosylated RTA? (ricin A
      chain non-toxic mutant). Tight interaction between AtPNG1(C251A) and the RTA? was
      confirmed by co-immunoprecipitation analysis. CONCLUSION: The plant PNGase
      facilitates ERAD through its deglycosylation activity, while the catalytic mutant
      of AtPNG1 impair glycoprotein ERAD by binding to N-glycans on the ERAD
      substrates. GENERAL SIGNIFICANCE: Our studies underscore the functional
      importance of a plant PNGase orthologue as a deglycosylating enzyme involved in
      the ERAD.

PMID- 22659525
TI  - Use of ultrasound for non-invasive assessment of flow-mediated dilation.
AB  - The pathological complications of atherosclerosis, namely heart attacks and
      strokes, remain the leading cause of mortality in the Western world. Preceding
      atherosclerosis is endothelial dysfunction. There is therefore interest in the
      application of non-invasive clinical tools to assess endothelial function. The
      flow-mediated dilation (FMD) test is the standard tool used to assess endothelial
      function. Reduced FMD is an early marker of atherosclerosis and has been noted
      for its capacity to predict future cardiovascular disease events. This review
      discusses the measurement of endothelial function using ultrasound, with a focus
      on the FMD technique.

PMID- 22659526
TI  - Low-dose calcitriol decreases aortic renin, blood pressure, and atherosclerosis
      in apoe-null mice.
AB  - AIMS: To determine whether low-dose calcitriol attenuates atherosclerosis in apoE
      null mice and, if so, through which predominant mechanism. METHODS: Starting at
      the age of 6 weeks, mice received intraperitoneal injections of either 0.25 ng/g
      body weight of calcitriol or the vehicle, every other day for 8 weeks. RESULTS:
      Calcitriol treatment resulted in 35% reduction of atherosclerosis at the aortic
      sinus, and in a significant decrease in blood pressure. These effects were
      possibly mediated by downregulation of the renin-angiotensin system (RAS), as
      there was a 64% decrease in the aortic level of renin mRNA. None of the other
      components of the RAS or the prorenin receptor were affected by treatment. Low
      dose calcitriol treatment did not modify the plasma level of monocyte
      chemoattractant protein-1, interferon gamma, interleukin-4 and interleukin-10,
      which were similar in control and treated mice. Likewise, there was no difference
      in the percentage of splenic Foxp3+ regulatory T cells. Calcitriol treatment
      resulted in an unfavorable metabolic profile (glucose and lipids), as determined
      after a limited fast, a difference that disappeared after food was withheld for a
      longer time. CONCLUSIONS: At a relatively low dosage, calcitriol attenuates the
      development of atherosclerosis in apoE-null mice, most probably by down
      regulation of RAS, and not through immunomodulation; however, even at this low
      dose, calcitriol appears to elevate calcium and to have potentially adverse
      metabolic effects. Exploring the potential antiatherogenic effects of non
      calcemic and safer analogues is therefore warranted.

PMID- 22659527
TI  - Elevated serum myeloperoxidase activities are significantly associated with the
      prevalence of ACS and High LDL-C levels in CHD patients.
AB  - AIM: Recent researches have shown that myeloperoxidase (MPO) is a potential
      inflammatory risk factor for coronary heart disease (CHD). In the present study,
      the possible associations of MPO with acute coronary syndrome (ACS), low density
      lipoprotein cholesterol (LDL-C) and other risk factors in CHD patients were
      investigated. METHODS: Five hundred thirty-six CHD patients [363 ACS and 173
      stable angina pectoris (SAP)] and 181 non-CHD patients confirmed by coronary
      angiography were enrolled in this study. The association study was performed by
      logistic regression analysis. RESULTS: ACS patients had significantly higher MPO
      activities than SAP and non-CHD patients (p < 0.001). The area under the receiver
      operating characteristic (ROC) curve of MPO for diagnosing ACS was 0.84 (95% CI:
      0.80-0.88, p < 0.001). The optimal cut-off value (sensitivity; specificity) of
      MPO was 164.77 ng/mL (79.1% and 82.1%). LDL-C (III versus I tertile, OR: 3.24,
      95% CI: 1.67-6.29, p = 0.001) and ACS (yes versus no, OR 2.74, 95% CI: 1.71-4.39,
      p < 0.001) were significantly associated with elevated serum MPO activities,
      which had the highest odds ratio in quantitative and qualitative variables,
      respectively. There were significant increase trends in the prevalence of ACS and
      high LDL-C levels from I to III MPO tertile, which were 46.4% and 8.9% for I,
      68.0% and 31.5% for II, 88.8% and 59.8% for III tertile, respectively (p <
      0.001). CONCLUSION: The present study provides epidemiological evidence that
      elevated serum MPO activities are significantly associated with the prevalence of
      ACS and high LDL-C levels in CHD patients, and MPO may be a potential early
      warning marker for ACS.

PMID- 22659528
TI  - Associations between small dense LDL, HDL subfractions (HDL2, HDL3) and risk of
      atherosclerosis in Japanese-Americans.
AB  - AIM: Small dense low-density lipoprotein (sdLDL) has been suggested to be more
      atherogenic than large buoyant LDL. High-density lipoprotein (HDL) consists of
      two major subfractions (HDL2, HDL3), and just as controversy remains regarding
      which of the two is the more powerful negative risk factor for atherosclerosis,
      associations between sdLDL and these HDL subfractions are unclear. METHODS: We
      measured sdLDL cholesterol (sdLDL-C), HDL2 cholesterol (HDL2-C) and HDL3
      cholesterol (HDL3-C) by a newly developed method in 481 Japanese-Americans who
      were not using lipid-lowering medication, and examined the associations of these
      cholesterol concentrations with variables related to atherosclerosis. RESULTS: In
      multivariate analysis, sdLDL-C was positively correlated with the body mass index
      (BMI), fasting glucose and insulin, 2-h glucose, HOMA-IR, high sensitivity C
      reactive protein (hsCRP), and carotid artery intima-media thickness (IMT) after
      adjustment for age and sex. In particular, sdLDL-C was positively correlated with
      IMT, even after adjustment for sex, age, smoking status, hypertension, diabetes
      mellitus and hsCRP. HDL2-C was more closely inversely correlated than total HDL-C
      with BMI, fasting glucose and insulin, 2-h glucose, HOMA-IR, and hsCRP, whereas
      HDL3-C was not correlated with these factors. Additionally, HDL2-C was more
      closely correlated than total HDL-C or HDL3-C with sdLDL-C, LDL-C, triglycerides
      (TG), and apolipoprotein B (apoB). CONCLUSIONS: SdLDL-C was closely associated
      with insulin resistance and glucose tolerance, lending credence to its potential
      as a useful risk marker in assessing carotid artery IMT and the present degree of
      atherosclerosis in Japanese-Americans. The findings also suggest that subjects
      with higher HDL2-C levels were better protected from atherosclerosis.

PMID- 22659529
TI  - Cardio-ankle vascular index in heterozygous familial hypercholesterolemia.
AB  - AIM: The cardio-ankle vascular index (CAVI) is a new non-invasive marker of
      arterial stiffness and atherosclerosis. The purpose of this study was to compare
      CAVI in patients with heterozygous familial hypercholesterolemia (FH) and in
      healthy controls. METHODS: 82 FH subjects (27 males, 65 females), aged 53.7+/
      13.6 years without clinical symptoms of cardiovascular diseases and 359 healthy
      controls (121 males, 238 females), aged 43.9+/-14.9 years, were examined. CAVI
      was measured using the system VaSera(r) 1500. RESULTS: CAVI in FH patients was
      significantly higher (8.0+/-1.4) than in healthy subjects (7.5+/-1.3) p = 0.002;
      however, age, sex and BMI adjusted CAVI did not differ significantly (p = 0.061)
      between the FH group (7.5, CI: 7.3; 7.7) and control group (7.7, CI: 7.6; 7.7).
      CONCLUSION: The study showed no significant difference in CAVI between
      heterozygous FH and healthy controls.

PMID- 22659530
TI  - The utility of visceral fat level by bioelectrical impedance analysis in the
      screening of metabolic syndrome - the results of the Kyushu and Okinawa
      Population Study (KOPS).
AB  - AIM: A simple, non-invasive medical device, using bioelectrical impedance
      analysis (BIA) for the evaluation of visceral fat level (VFL) was developed
      recently. The aim of this study was to investigate the utility of VFL by BIA in
      the screening of metabolic syndrome (MetS). METHODS: VFL was measured by the BIA
      device in 1,451 Japanese residents (546 men and 905 women, age range 30-69
      years). RESULTS: VFL had significant positive correlations with waist
      circumference (WC) and body mass index (r=0.772 and 0.849, all P < 0.0001). The
      overall MetS prevalence using Japanese Diagnosis Criteria was 19.8%: men 36.3%
      and women 9.8%. The mean VFL of the participants with MetS was significantly
      higher than those without MetS (men; 12.1 and 9.4, women; 13.3 and 8.7) (both P <
      0.001). VFL significantly correlated with blood pressure, lipid profiles, fasting
      plasma glucose, and hemoglobin A1c (all P < 0.001). Receiver operating
      characteristic curve analysis for a diagnosis of two or more MetS risk factors
      excluding WC resulted in the same cutoff values for the VFL (10.0) of men and
      women. CONCLUSIONS: The VFL by BIA is useful for the detection of MetS because it
      is correlated with all metabolic parameters and shows the same normal limit in
      both sexes.

PMID- 22659531
TI  - A prothrombotic state is associated with early arterial damage in hypertensive
      patients.
AB  - AIM: A prothrombotic state is associated with organ damage in hypertensive
      patients. Carotid intima-media thickness (IMT) is an early marker of vascular
      damage that anticipates the development of atherosclerotic plaques. The aim of
      the present study was to investigate the relationships between subclinical
      carotid damage and markers of the prothrombotic state in hypertension. METHODS:
      In 258 essential hypertensive patients who were consecutively recruited at a
      hypertension clinic an ultrasound carotid scan was performed with assessment of
      the IMT and plasma levels of C-reactive protein, fibrinogen, fibrin D-dimer,
      prothrombin fragment 1+2, homocysteine, and lipoprotein(a) were measured.
      RESULTS: Patients with an IMT above the median of the distribution (800 um) were
      older and had greater BMI, pulse pressure, duration of hypertension, and
      prevalence of coronary heart disease than patients with an IMT below the median.
      Patients with higher IMT had also greater levels of C-reactive protein,
      fibrinogen, fibrin D-dimer, and homocysteine. Regression analysis showed a direct
      relationship of IMT with age, waist circumference, pulse pressure, fibrinogen,
      fibrin D-dimer, and number of cigarettes smoked per day, and an inverse
      relationship with creatinine clearance. On multivariate analysis, age, pulse
      pressure, and fibrin D-dimer were independently related with IMT. CONCLUSION: In
      hypertensive patients, subclinical carotid damage is related with evidence of
      activated coagulation system suggesting a prothrombotic state. This might
      contribute to the development of hypertensive arterial damage even in the
      earliest stages.

PMID- 22659532
TI  - Acute decrease of cardio-ankle vascular index with the administration of
      beraprost sodium.
AB  - AIM: A novel arterial stiffness index, the cardio-ankle vascular index (CAVI),
      has been proposed. To clarify the properties of CAVI, the effects of beraprost
      sodium (BPS), a prostaglandin (PG) I2 analogue, which has a potent vasodilating
      effect, on CAVI were studied and comparing with brachialankle pulse wave velocity
      (baPWV) in healthy volunteers. METHODS: Male volunteers (n=18, 46.3+/-4.2 yr)
      were enrolled in this study and administered BPS (40 ug). CAVI and baPWV were
      measured every hour for 4 hours. RESULTS: When BPS was administered to 18 healthy
      volunteers, systolic blood pressure and diastolic blood pressure fluctuated
      slightly, but the means did not change. CAVI significantly decreased in the 1st
      hour from 8.3+/-0.34 (mean+/-SE) to 7.9+/-0.34 (p<0.05) and this decrease
      persisted for 3 hours, whereas baPWV did not significantly change. DeltabaPWV
      each time was significantly correlated with both Deltasystolic blood pressure and
      Deltadiastolic blood pressure, but DeltaCAVI did not correlate with either
      Deltasystolic blood pressure (r=-0.12, p=0.38) or Deltadiastolc blood pressure
      (r=-0.22, p=0.10). CONCLUSIONS: Beraprost sodium did not decrease blood pressure,
      but decreased CAVI, whereas baPWV did not change. These results indicate that
      CAVI partly reflected the contraction of arterial smooth muscle cells.

PMID- 22659534
TI  - Appearance of WBC-platelet complex in acute ischemic stroke, predominantly in
      atherothrombotic infarction.
AB  - AIM: Platelet aggregates with white blood cells (WBC-platelet complex) have
      recently been proposed as a marker of activated platelets, in addition to well
      known molecular markers. We aimed to investigate the colocalization of activated
      platelets and WBC-platelet complex by means of flow cytometry, in patients with
      ischemic stroke. METHODS: Eighty-six patients with cerebral infarction (CI) in
      the acute phase (58 males, 28 females; 65+/-14 years old) and 62 non-CI controls
      (23 males, 39 females; 53+/-14 years old) were registered. The appearance of WBC
      platelet complex was quantified using 3-color flow cytometry. RESULTS: The
      appearance rate of WBC-platelet complex was significantly higher in the CI group
      than in the controls. The appearance rate of WBC-platelet complex was
      significantly higher in atherothrombotic infarction (AT) than in lacunar
      infarction (LA) (p < 0.05). Furthermore, positive rates of both monocyte-platelet
      complex and granulocyte-platelet complex, but not lymphocyte-platelet complex,
      were significantly higher in the AT group than in the controls. CONCLUSION: We
      concluded that WBC-platelet complex, especially involving monocytes and
      granulocytes, is a novel marker of platelet activation in the acute phase of
      ischemic stroke, mainly in AT.

PMID- 22659533
TI  - Double-dose pravastatin versus add-on ezetimibe with low-dose pravastatin -
      effects on LDL cholesterol, cholesterol absorption, and cholesterol synthesis in
      Japanese patients with hypercholesterolemia (PEAS study).
AB  - AIM: This study compared the effect of doubling the dose of pravastatin with that
      of adding ezetimibe to low-dose pravastatin on the LDL cholesterol (LDL-C) level
      and on cholesterol absorption and synthesis markers. The tolerability of the 2
      regimens was also compared. METHODS: This was a multicenter, open-label, parallel
      group trial. Subjects were aged from 20 to 74 years and had an LDL-C >= 120 mg/dL
      despite pravastatin therapy at 5-10 mg/day. They were randomly allocated to
      receive either add-on ezetimibe (10 mg/day) or double-dose pravastatin, and
      follow-up was performed for 12 weeks. The primary endpoints were the changes of
      LDL-C and apolipoprotein (apo) B levels after 12 weeks of treatment. Cholesterol
      absorption and synthesis markers were also determined. RESULTS: LDL-C and apo B
      decreased by 16% and 14% in the ezetimibe add-on group versus 5.9% and 4.4%,
      respectively, in the pravastatin double-dose group. The between-group differences
      of these decreases were highly significant. Cholesterol absorption markers
      (sitosterol, campesterol, and cholestanol) were reduced by 48%, 36%, and 10%,
      respectively, in the ezetimibe add-on group, and were increased by 17%, 14%, and
      6%, respectively, in the pravastatin double-dose group. Lathosterol (a
      cholesterol synthesis marker) increased by 76% in the ezetimibe add-on group and
      by 24% in the pravastatin double-dose group. The difference was statistically
      significant. No serious adverse effect was observed in either group. CONCLUSIONS:
      Adding ezetimibe to low-dose pravastatin achieves greater decreases in LDL-C, apo
      B, and cholesterol absorption markers than doubling the dose of pravastatin.

PMID- 22659535
TI  - Von Hippel-Lindau: how a rare disease illuminates cancer biology.
AB  - Von Hippel-Lindau (VHL) disease is a rare autosomal dominant syndrome (1/36,000
      live births) with highly penetrance that predispose to the development of a panel
      of highly vascularized tumors (model of tumoral angiogenesis). Main
      manifestations include central nervous system (CNS) and retinal
      haemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas
      (RCC), phaeochromocytomas and pancreatic neuroendocrine tumors. RCC has become
      the first potential cause of mortality and VHL disease is the main cause of
      inherited RCC. The disease is caused by germline mutations in the VHL tumor
      suppressor gene that plays a major role in regulation of the oxygen-sensing
      pathway by targeting the hypoxia-inducible factor HIF for degradation in
      proteasome. VHL has also major HIF-independent functions, specially in regulation
      of primary cilium, extracellular matrix and apoptosis. Somatic inactivation of
      the VHL gene is the main molecular event in most sporadic RCC and the treatment
      of advanced RCC has been revolutionized by targeted therapy with drugs that block
      angiogenesis. These drugs are now in first line in metastatic sporadic RCC and
      have shown promising results for RCC, pancreatic neuroendocrine tumors and
      malignant pheochromocytomas in VHL patients.

PMID- 22659537
TI  - Changes in objectively measured physical activity (performance) after epidural
      steroid injection for lumbar spinal stenosis.
AB  - OBJECTIVE: To examine changes in objectively measured physical activity
      (performance) at 1 week following epidural steroid injection for lumbar spinal
      stenosis. DESIGN: Prospective cohort. SETTING: University spine program.
      PARTICIPANTS: Individuals (N=17) who were undergoing fluoroscopically guided
      epidural steroid injection for symptomatic lumbar spinal stenosis (mean age +/-
      SD, 70.1+/-6.7; 47% women). INTERVENTION: Fluoroscopically guided epidural
      injection. MAIN OUTCOME MEASURE(S): The 2 primary outcomes, measured with
      accelerometers, were total activity (performance) measured over 7 days and
      maximum continuous activity (capacity). Walking capacity was also assessed with
      the Self-Paced Walking Test, and subjects completed the Oswestry Disability
      Index, Swiss Spinal Stenosis Questionnaire, Medical Outcomes Study 36-Item Short
      Form Health Survey, visual analog pain scales, and body diagrams. RESULTS: At 1
      week postinjection, 58.8% of the subjects demonstrated increased total activity
      and 53% had increased maximum continuous activity, although neither change was
      statistically significant. Significant improvements were observed in a number of
      the self-report instruments, including the Physical Function Scale of the Swiss
      Spinal Stenosis Questionnaire, general health (Medical Outcomes Study 36-Item
      Short-Form Health Survey), role-limitation emotional (Medical Outcomes Study 36
      Item Short-Form Health Survey), leg pain intensity (visual analog pain scales),
      and presence of leg weakness. CONCLUSIONS: While patients perceived improvements
      in pain and function following injection, these improvements were not reflected
      in significant changes in performance or capacity. Future studies will continue
      to find value in subjective measures of pain and quality of life. However, with
      modern technology, performance is no longer a subjective variable. Use of
      activity monitors to objectively measure performance can result in more rigorous
      validation of treatment effects, while simultaneously highlighting the potential
      need for additional postinjection rehabilitation aimed at improving performance.

PMID- 22659536
TI  - Active-assisted cycling improves tremor and bradykinesia in Parkinson's disease.
AB  - OBJECTIVES: To develop a rapid cadence cycling intervention (active-assisted
      cycling [AAC]) using a motorized bike and to examine physiological perimeters
      during these sessions in individuals with Parkinson's disease (PD). A secondary
      goal was to examine whether a single session of AAC at a high cadence would
      promote improvements in tremor and bradykinesia similar to the on medication
      state. DESIGN: Before-after pilot trial with cross-over. SETTING: University
      research laboratory. PARTICIPANTS: Individuals with idiopathic PD (N=10, age 45
      74y) in Hoehn and Yahr stages 1 to 3. INTERVENTION: Forty minutes of AAC. MAIN
      OUTCOME MEASURES: Heart rate, pedaling power, and rating of perceived exertion
      were recorded before, during, and after a bout of AAC. Functional assessments
      included tremor score during resting, postural, and kinetic tremor. RESULTS: This
      AAC paradigm was well tolerated by individuals with PD without excessive fatigue,
      and most participants showed improvements in tremor and bradykinesia immediately
      after a single bout of cycling. CONCLUSIONS: This paradigm could be used to
      examine changes in motor function in individuals with PD after bouts of high
      intensity exercise.

PMID- 22659538
TI  - Characteristics of AZD9708, a novel, selective beta2-adrenoceptor agonist with
      rapid onset and long duration of action.
AB  - Here we describe the pre-clinical pharmacological profile of AZD9708, a novel
      long-acting beta(2)-adrenoceptor agonist that has potential as a once-daily
      therapy for asthma and chronic obstructive pulmonary disease (COPD). AZD9708 is a
      potent and selective agonist at the human beta(2)-adrenoceptor, with selectivity
      over human beta(1)- and beta(3)-adrenoceptors of >500 and >24 fold, respectively.
      AZD9708 relaxes carbachol-induced contraction of human bronchial rings with a
      time to 90% of maximal relaxation of 13-20 min, similar to that seen with
      formoterol and quicker than salmeterol. In anesthetized guinea pigs, AZD9708
      provides significant protection against histamine-induced airway constriction at
      24 h after intratracheal and nebulized doses. This is longer than with
      intratracheal salmeterol, which is bronchoprotective for approximately 8 h, and
      formoterol, which is bronchoprotective for 8 and 12 h following nebulized and
      intratracheal dosing, respectively. AZD9708 also shows the potential for a
      greater therapeutic margin than widely used beta(2)-adrenoceptor agonists such as
      formoterol. At a defined efficacy dose that provides 80% bronchoprotection
      (ED(80)), formoterol leads to a decrease in blood potassium levels in guinea
      pigs, whilst AZD9708 is not associated with significant reductions in potassium
      levels at doses up to 7 times the ED(80). [(14)C]AZD9708 is associated with
      extensive protein binding in both human (mean 1.0% free) and rat (mean 2.6% free)
      plasma. This pharmacological profile indicates the potential of AZD9708 to become
      an important addition to the range of bronchodilators available for the treatment
      of patients with obstructive airways disease.

PMID- 22659539
TI  - Expression of a recombinant Phoneutria toxin active in calcium channels.
AB  - PnTx3-4 is a toxin isolated from the venom of the spider Phoneutria nigriventer
      that blocks N-, P/Q-, and R-type voltage-gated calcium channels and has great
      potential for clinical applications. In this report we used the SUMO system to
      express large amounts of recombinant PnTx3-4 peptide, which was found in both
      soluble and insoluble fractions of bacterial extracts. We purified the
      recombinant toxin from both fractions and showed that the recombinant peptide
      showed biological activity similar to the native PnTx3-4. In silico analysis of
      the primary sequence of PnTx3-4 indicated that the peptide conforms to all the
      criteria of a knottin scaffold. Additionally, circular dichroism spectrum
      analysis of the recombinant PnTx3-4 predicted that the toxin structure is
      composed of approximately 53% turns/unordered, 31% alpha-helix and 16% beta
      strand, which is consistent with predicted model of the PnTx3-4 knottin scaffold
      available at the knottin database (http://knottin.cbs.cnrs.fr). These studies
      provide the basis for future large scale production and structure-function
      investigation of PnTx3-4.

PMID- 22659541
TI  - Upregulation of the vascular endothelial growth factor, Flt-1, in rat hippocampal
      neurons after envenoming by Phoneutria nigriventer; age-related modulation.
AB  - This study characterizes the distribution and quantifies the expression of the
      tyrosine kinase receptor for the vascular endothelial growth factor (VEGF), Flt
      1, in the rat hippocampus following intra-peritoneal injection of Phoneutria
      nigriventer venom (PNV). Post-natal day 14 (P14) and 8-10 weeks (adult) old rats
      were used and analyses were done at 1, 2, 5 and 24 h after venom exposure and
      compared with saline-injected counterparts. PNV-injected animals showed
      hippocampal venules with perivascular edema indicating blood-brain barrier (BBB)
      dysfunction. This was accompanied by significant overexpression of Flt-1 which
      though was not the same for CA1, CA2, CA3 and dentate gyrus (DG) hippocampal
      regions, neither for P14 and adult rats. Regional analysis using GIMP methodology
      showed that Flt-1 was constitutively distributed more densely in neurons of DG,
      followed by CA1/CA2 and CA3 of both control P14 and adult animals, without
      variation over time, but significantly more expressed in P14 than in adults. A
      time-course analysis showed that Flt-1 upregulation was progressive and that
      neurons VEGFR1/Flt-1+ of PNV-exposed animals are timely and regionally modulated
      depending on the hippocampal region, being CA2 the least responsive region
      regardless animal's age, whilst DG was the most susceptible with adult animals
      having higher upregulation than neonates. Since VEGF has been reported to confer
      protection in several pathological processes we suggest that VEGF may be involved
      in hippocampal neurons response via Flt-1 mediation following PNV envenoming; its
      higher upregulation in adult envenomed rats may be an indication that Flt-1
      neuroprotective mediation is more efficient with age. The Flt-1 upregulation and
      the incidence of perivascular edema in young animals may indicate a pro
      inflammatory role of the receptor.

PMID- 22659540
TI  - Expression and isotopic labelling of the potassium channel blocker ShK toxin as a
      thioredoxin fusion protein in bacteria.
AB  - The polypeptide toxin ShK is a potent blocker of Kv1.3 potassium channels, which
      play a crucial role in the activation of human effector memory T-cells (T(EM)).
      Selective blockers constitute valuable therapeutic leads for the treatment of
      autoimmune diseases mediated by T(EM) cells, such as multiple sclerosis,
      rheumatoid arthritis, and type-1 diabetes. We have established a recombinant
      peptide expression system in order to generate isotopically-labelled ShK and
      various ShK analogues for in-depth biophysical and pharmacological studies. ShK
      was expressed as a thioredoxin fusion protein in Escherichia coli BL21 (DE3)
      cells and purified initially by Ni2+ iminodiacetic acid affinity chromatography.
      The fusion protein was cleaved with enterokinase and purified to homogeneity by
      reverse-phase HPLC. NMR spectra of 15N-labelled ShK were similar to those
      reported previously for the unlabelled synthetic peptide, confirming that
      recombinant ShK was correctly folded. Recombinant ShK blocked Kv1.3 channels with
      a K(d) of 25 pM and inhibited the proliferation of human and rat T lymphocytes
      with a preference for T(EM) cells, with similar potency to synthetic ShK in all
      assays. This expression system also enables the efficient production of 15N
      labelled ShK for NMR studies of peptide dynamics and of the interaction of ShK
      with Kv1.3 channels.

PMID- 22659542
TI  - A sensitive assay for palytoxins, ovatoxins and ostreocins using LC-MS/MS
      analysis of cleavage fragments from micro-scale oxidation.
AB  - Palytoxin is a highly toxic non-proteinaceous marine natural product that can
      pass through the food chain and result in human illnesses. A recent review by the
      European Food Safety Authority concluded that palytoxin requires regulation in
      seafood and a limit of 30 MUg kg-1 for shellfish flesh was suggested. Current
      methods based on LC-MS detection of intact palytoxins do not have sufficient
      sensitivity to enforce this limit for palytoxin. To improve sensitivity for trace
      analysis, a novel screen approach has been developed that uses LC-MS/MS analysis
      of substructures generated by oxidative cleavage of vicinal diol groups present
      in the intact toxin. Oxidation of palytoxins, ovatoxins or ostreocins using
      periodic acid generates two nitrogen-containing aldehyde fragments; an amino
      aldehyde common to these toxins, and an amide aldehyde that may vary depending on
      toxin type. Conditions for micro-scale oxidation of palytoxin were optimised,
      which include a novel SPE cleanup and on-column oxidation step. Rapid analysis of
      cleavage fragments was established using LC-MS/MS. Linear calibrations were
      established for the amino aldehyde from a palytoxin reference standard, which is
      suitable for all known palytoxin-like compounds, and for the confirmatory amide
      aldehydes of palytoxin and ostreocin-D. Palytoxin recoveries (at 10 MUg kg-1)
      from shellfish and fish tissues were 114-119% (as amine aldehyde) and 90-115% (as
      amide aldehyde) with RSDs for both of <= 18% (all tissues, n = 12). The method
      LOD was determined to be approximately 1 ng mL-1 and the LOQ 4 ng mL-1, which
      corresponds to 10 MUg kg-1 in tissue (flesh of shellfish or fish). The method has
      potential for use in research and is sufficiently sensitive for regulatory
      testing, should it be required.

PMID- 22659543
TI  - Neural crest contribution to lingual mesenchyme, epithelium and developing taste
      papillae and taste buds.
AB  - The epithelium of mammalian tongue hosts most of the taste buds that transduce
      gustatory stimuli into neural signals. In the field of taste biology, taste bud
      cells have been described as arising from "local epithelium", in distinction from
      many other receptor organs that are derived from neurogenic ectoderm including
      neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme
      in the developing tongue is not fully understood. In the present study we used
      two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express
      Cre recombinase in a NC-specific manner, in combination with two Cre reporter
      mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to
      both tongue mesenchyme and epithelium including taste papillae and taste buds. In
      tongue mesenchyme, distribution of NC-derived cells is in close association with
      taste papillae. In tongue epithelium, labeled cells are observed in an initial
      scattered distribution and progress to a clustered pattern between papillae, and
      within papillae and early taste buds. This provides evidence for a contribution
      of NC to lingual epithelium. Together with previous reports for the origin of
      taste bud cells from local epithelium in postnatal mouse, we propose that NC
      cells migrate into and reside in the epithelium of the tongue primordium at an
      early embryonic stage, acquire epithelial cell phenotypes, and undergo cell
      proliferation and differentiation that is involved in the development of taste
      papillae and taste buds. Our findings lead to a new concept about derivation of
      taste bud cells that include a NC origin.

PMID- 22659544
TI  - We are number one but nobody cares-that's good.

PMID- 22659545
TI  - Linking data and models: the importance of statistical analyses to inform models
      for the transmission dynamics of infections.

PMID- 22659547
TI  - The role of measurement error and misclassification in mediation analysis: 
      mediation and measurement error.

PMID- 22659546
TI  - Cholera modeling: challenges to quantitative analysis and predicting the impact
      of interventions.
AB  - Several mathematical models of epidemic cholera have recently been proposed in
      response to outbreaks in Zimbabwe and Haiti. These models aim to estimate the
      dynamics of cholera transmission and the impact of possible interventions, with a
      goal of providing guidance to policy makers in deciding among alternative courses
      of action, including vaccination, provision of clean water, and antibiotics.
      Here, we discuss concerns about model misspecification, parameter uncertainty,
      and spatial heterogeneity intrinsic to models for cholera. We argue for caution
      in interpreting quantitative predictions, particularly predictions of the
      effectiveness of interventions. We specify sensitivity analyses that would be
      necessary to improve confidence in model-based quantitative prediction, and
      suggest types of monitoring in future epidemic settings that would improve
      analysis and prediction.

PMID- 22659548
TI  - Household air pollution and children's blood pressure.

PMID- 22659549
TI  - Only coarse particles from the Sahara?

PMID- 22659550
TI  - Sleep disorders and traffic accidents.

PMID- 22659551
TI  - Specifying the correlation structure in inverse-probability- weighting estimation
      for repeated measures.

PMID- 22659552
TI  - Software for unbiased estimation of attributable risk.

PMID- 22659553
TI  - Cell phone use and crash risk.

PMID- 22659554
TI  - Cell phone use and crash risk.

PMID- 22659556
TI  - Transmissibility of influenza.

PMID- 22659558
TI  - On compulsory preregistration of protocols.

PMID- 22659560
TI  - The long-run distribution of births across environments under environmental
      stochasticity and its use in the calculation of unconditional life-history
      parameters.
AB  - Matrix population models assume individuals develop in time along different
      stages that may include age, size or degree of maturity to name a few. Once in a
      given stage, an individual's ability to survive, reproduce or move to another
      stage are fixed for that stage. Some demographic models consider that
      environmental conditions may change, and thus the chances of reproducing, dying
      or developing to another stage depend on the current stage and environmental
      conditions. That is, models have evolved from a single transition matrix to a set
      of several transition matrices, each accounting for the properties of a given
      environment. These models require information on the transition between
      environments, which is in general assumed to be Markovian. Although great
      progress has been made in the analysis of these models, they present new
      challenges and some new parameters need to be calculated, mainly the ones related
      to how births are distributed among environments. These parameters may help in
      population management and to calculate unconditional life history parameters. We
      derive for the first time an expression for the long-run distribution of births
      across environments, and show that it does not depend only on the long-range
      frequency of different environments, but also on the set of all transition and
      fertility matrices. We also derive the long-run distribution of deaths across
      environments. We provide an example using a real data set of the dynamics of
      Saiga antelope. Theoretical values closely match the observed values obtained in
      a large set of stochastic simulations.

PMID- 22659561
TI  - Left ventricular pressure, contractility and dP/dt(max) in nonclinical drug
      safety assessment studies.
AB  - Increasing or decreasing cardiac contractility is an undesirable property of
      drugs being developed for noncardiovascular indications. The International
      Conference on Harmonization (ICH) Topic S7A and S7B guidelines only require the
      assessment of heart rate, blood pressure and the electrocardiogram in nonclinical
      in vivo safety pharmacology studies. Assessment of drug effects on contractility
      is only suggested as an optional follow-up study. However, these nonclinical
      safety assessment studies can detect these effects if properly designed and
      conducted using appropriate instrumentation. Left ventricular dP/dt is the first
      derivative of left ventricular pressure, which is computed by software algorithms
      by using calculus. Its peak value, dP/dt(max), is a common, robust and sensitive
      indicator of changes in cardiac contractility if experimental parameters such as
      preload, afterload and heart rate are well controlled. In order to ensure
      accuracy and avoid errors in the measurement of contractility in experimental
      animals, the frequency response of the pressure sensing system and the sample
      rate of the data acquisition system must be optimized for the signal. For dogs,
      nonhuman primates, and normotensive rats, all important information in a left
      ventricular pressure signal can be captured with a system with a frequency
      response of 100 Hz. Although systems with much higher frequency response can be
      used to measure left ventricular pressure, the output of these devices must be
      filtered to allow no frequencies to be acquired that are higher than one-half the
      sample rate of the acquisition system. Stated conversely, the sample rate of the
      acquisition system must be at least 2* the highest frequency contained in the
      signal. Failure to follow these principals can lead to incorrect results due to
      measurement artifacts from high frequency noise, which could be present but not
      detectable by the investigator. This manuscript has been written for biologists
      who do not have advanced knowledge of physics and/or engineering and is therefore
      less technical and more simplified than what would be found in the engineering
      literature.

PMID- 22659562
TI  - Validating a behavioral economic approach to assess food demand: effects of body
      mass index, dietary restraint, and impulsivity.
AB  - Behavioral economic theory is a useful framework for analyzing factors
      influencing choice, but the majority of human behavioral economic research has
      focused on drug choice. The behavioral economic choice paradigm may also be
      valuable for understanding food-maintained behavior. Our primary objective was
      two-fold: (1) Validate a human laboratory model of food-appetitive behavior, and
      (2) Assess the contribution of individual level factors that may differentially
      impact food choice behavior. Two studies were conducted. In Study 1, female
      subjects (N=17) participated in two consecutive food choice experimental
      sessions, whereas in Study 2, female subjects (N=21) participated in one
      concurrent food choice experimental session. During consecutive choice sessions
      (Study 1), demand for the more palatable food (i.e., high-sugar/high-fat) was
      more inelastic than the less palatable (i.e., low-sugar/low-fat) option. During
      concurrent choice sessions, demand for the more palatable food (i.e., high
      sugar/high-fat) was more inelastic for restrained vs. unrestrained eaters, and
      for those who were overweight vs. normal weight. Demand for both palatable and
      less palatable choices was more elastic for high-impulsive vs. low-impulsive
      subjects. These findings suggest that the behavioral economic framework can be
      used successfully to develop a human laboratory model of food-appetitive
      behavior.

PMID- 22659563
TI  - Proteome analysis reveals protein candidates involved in early stages of brain
      regeneration of teleost fish.
AB  - Exploration of the molecular dynamics underlying regeneration in the central
      nervous system of regeneration-competent organisms has received little attention
      thus far. By combining a cerebellar lesion paradigm with differential proteome
      analysis at a post-lesion survival time of 30 min, we screened for protein
      candidates involved in the early stages of regeneration in the cerebellum of such
      an organism, the teleost fish Apteronotus leptorhynchus. Out of 769 protein
      spots, the intensity of 26 spots was significantly increased by a factor of at
      least 1.5 in the lesioned hemisphere, relative to the intact hemisphere. The
      intensity of 9 protein spots was significantly reduced by a factor of at least
      1.5. The proteins associated with 15 of the spots were identified by peptide mass
      fingerprinting and/or tandem mass spectrometry, resulting in the identification
      of a total of 11 proteins. Proteins whose abundance was significantly increased
      include: erythrocyte membrane protein 4.1N, fibrinogen gamma polypeptide,
      fructose-biphosphate aldolase C, alpha-internexin neuronal intermediate filament
      protein, major histocompatibility complex class I heavy chain, 26S proteasome non
      ATPase regulatory subunit 8, tubulin alpha-1C chain, and ubiquitin-specific
      protease 5. Proteins with significantly decreased levels of abundance include:
      brain glycogen phosphorylase, neuron-specific calcium-binding protein
      hippocalcin, and spectrin alpha 2. We hypothesize that these proteins are
      involved in energy metabolism, blood clotting, electron transfer in oxidative
      reactions, cytoskeleton degradation, apoptotic cell death, synaptic plasticity,
      axonal regeneration, and promotion of mitotic activity.

PMID- 22659565
TI  - Reconsolidation involves histone acetylation depending on the strength of the
      memory.
AB  - Gene expression is a necessary step for memory re-stabilization after retrieval,
      a process known as reconsolidation. Histone acetylation is a fundamental
      mechanism involved in epigenetic regulation of gene expression and has been
      implicated in memory consolidation. However, few studies are available in
      reconsolidation, all of them in vertebrate models. Additionally, the recruitment
      of histone acetylation as a function of different memory strengths has not been
      systematically analyzed before. Here we studied the role of histone acetylation
      in reconsolidation using a well-characterized memory model in invertebrate, the
      context-signal memory in the crab Chasmagnathus. Firstly, we found an increase in
      histone H3 acetylation 1h after memory reactivation returning to basal levels at
      3 h. Strikingly, this increment was only detected during reconsolidation of a
      long-term memory induced by a strong training of 30 trials, but not for a short
      term memory formed by a weak training of five trials or for a long-term memory
      induced by a standard training of 15 trials. Furthermore, we showed that a weak
      memory which was enhanced during consolidation by histone deacetylases
      inhibition, also recruited histone H3 acetylation in reconsolidation as the
      strong training does. Accordingly, we found the first evidence that the
      administration of a histone acetyl transferase inhibitor during memory
      reconsolidation impairs long-term memory re-stabilization. Finally, we found that
      strong training memory, at variance with the standard training memory, was
      resistant to extinction, indicating that such strong training induced in fact a
      stronger memory. In conclusion, the results presented here support that the
      participation of histone acetylation during reconsolidation is an evolutionary
      conserved feature and constitutes a specific molecular characteristic of strong
      memories.

PMID- 22659564
TI  - The clustered protocadherins Pcdhalpha and Pcdhgamma form a heteromeric complex
      in zebrafish.
AB  - The clustered protocadherin genes encode a diverse collection of neuronal cell
      surface receptors. These genes have been proposed to play roles in axon
      targeting, synaptic development and neuronal survival, although their specific
      cellular roles remain poorly defined. In zebrafish there are four clustered
      protocadherin genes, two pcdhalpha clusters and two pcdhgamma clusters, that give
      rise to over 100 distinct proteins, each with a distinct ectodomain (EC). The
      zebrafish is an excellent model in which to address the function of
      protocadherins during neural development, as the embryos are transparent, develop
      rapidly, and are amenable to experimental manipulation. As a first step to
      investigating the clustered protocadherins during zebrafish development, we have
      generated antibodies against the common cytodomains of zebrafish Pcdhgamma. We
      compare the distribution of Pcdhgamma with Pcdhalpha and find a similar pan
      neuronal pattern, with strong labeling of neurons within all major regions of the
      central nervous system. Pcdhalpha and Pcdhgamma are particularly enriched in the
      developing visual system, with strong labeling found in the synaptic layers of
      the retina, as well as the optic tectum. Consistent with studies in mouse, we
      find that Pcdhalpha and Pcdhgamma are present in a complex, as they can be co
      immunoprecipitated from zebrafish larval extracts. This interaction is direct and
      occurs through the ECs of these proteins. Using standard bead aggregation assays,
      we find no evidence for intrinsic adhesive ability by either Pcdhgamma or
      Pcdhalpha, suggesting that they do not function as cell adhesion molecules.

PMID- 22659566
TI  - Erythropoietin effect on sensorimotor recovery after contusive spinal cord
      injury: an electrophysiological study in rats.
AB  - Spinal cord injury (SCI) is a debilitating clinical condition, characterized by a
      complex of neurological dysfunctions. It has been shown in rats that the acute
      administration of recombinant human erythropoietin (rhEPO) following a contusive
      SCI improves the recovery of hindlimb motor function, as measured with the
      locomotor BBB (Basso, Beattie, Bresnahan) scale. This scale evaluates overall
      locomotor activity, without testing whether the rhEPO-induced motor recovery is
      due to a parallel recovery of sensory and/or motor pathways. Aim of the present
      study was to utilize an electrophysiological test to evaluate, in a rat model of
      contusive SCI, the transmission of both ascending and descending pathways across
      the damaged cord at 2, 5, 7, 11, and 30 days after lesion, in animals treated
      with rhEPO (n=25) vs saline solution (n=25). Motor potentials evoked by
      epicortical stimulation were recorded in the spinal cord, and sensory-evoked
      potentials evoked by spinal stimulation were recorded at the cortical level. In
      the same animals BBB score and immunocytochemical evaluation of the spinal
      segments caudal to the lesion were performed. In rhEPO-treated animals results
      show a better general improvement both in sensory and motor transmission through
      spared spinal pathways, supposedly via the reticulo-spinal system, with respect
      to saline controls. This improvement is most prominent at relatively early times.
      Overall these features show a parallel time course to the changes observed in BBB
      score, suggesting that EPO-mediated spared spinal cord pathways might contribute
      to the improvement in transmission which, in turn, might be responsible for the
      recovery of locomotor function.

PMID- 22659567
TI  - Robustness, variability, phase dependence, and longevity of individual synaptic
      input effects on spike timing during fluctuating synaptic backgrounds: a modeling
      study of globus pallidus neuron phase response properties.
AB  - A neuron's phase response curve (PRC) shows how inputs arriving at different
      times during the spike cycle differentially affect the timing of subsequent
      spikes. Using a full morphological model of a globus pallidus (GP) neuron, we
      previously demonstrated that dendritic conductances shape the PRC in a spike
      frequency-dependent manner, suggesting different functional roles of perisomatic
      and distal dendritic synapses in the control of patterned network activity. In
      the present study we extend this analysis to examine the impact of
      physiologically realistic high conductance states on somatic and dendritic PRCs
      and the time course of spike train perturbations. First, we found that average
      somatic and dendritic PRCs preserved their shapes and spike frequency dependence
      when the model was driven by spatially-distributed, stochastic conductance inputs
      rather than tonic somatic current. However, responses to inputs during specific
      synaptic backgrounds often deviated substantially from the average PRC.
      Therefore, we analyzed the interactions of PRC stimuli with transient
      fluctuations in the synaptic background on a trial-by-trial basis. We found that
      the variability in responses to PRC stimuli and the incidence of stimulus-evoked
      added or skipped spikes were stimulus-phase-dependent and reflected the profile
      of the average PRC, suggesting commonality in the underlying mechanisms. Clear
      differences in the relation between the phase of input and variability of spike
      response between dendritic and somatic inputs indicate that these regions
      generally represent distinct dynamical subsystems of synaptic integration with
      respect to influencing the stability of spike time attractors generated by the
      overall synaptic conductance.

PMID- 22659569
TI  - Enhanced cytotoxic activity of a bifunctional chimeric protein containing a type
      1 ribosome-inactivating protein and a serine protease inhibitor.
AB  - Both ribosome-inactivating proteins (RIPs) and plant proteinase inhibitors,
      belong to protein families known to regulate cellular homeostasis and likely
      involved in plant defense. Nevertheless the interest in these protein classes is
      due to their potential use for the treatment of several important human diseases
      such as cancer. Thus, in the present study, type 1 ribosome-inactivating protein
      and wheat subtilisin/chymotrypsin inhibitor, were engineered into a chimeric
      protein with cytotoxic action selective for murine tumor cells, while lacking any
      appreciable toxicity on murine normal cells. This chimeric protein selectively
      sensitizes to apoptotic death cells derived from Simian-virus-40-transformed
      mouse fibroblasts (SVT2 cells). The cytotoxicity of this new recombinant product
      has been detected also on three different human malignant cells. Therefore action
      on tumor cells of this protein could represent a potentially very attractive
      novel tool for anticancer drug design.

PMID- 22659568
TI  - L-DOPA-induced dysregulation of extrastriatal dopamine and serotonin and
      affective symptoms in a bilateral rat model of Parkinson's disease.
AB  - Convergent evidence indicates that raphestriatal serotonin (5-HT) neurons can
      convert and release dopamine (DA) derived from exogenous administration of the
      pharmacotherapeutic L-3,4-dihydroxyphenyl-L-alanine (L-DOPA) as a treatment for
      Parkinson's disease (PD). While aspects of such neuroplasticity may be
      beneficial, chronic L-DOPA may also modify native 5-HT function, precipitating
      the appearance prevalent non-motor PD symptoms such as anxiety and depression. To
      examine this, male Sprague-Dawley rats were rendered parkinsonian with bilateral
      medial forebrain bundle 6-hydroxydopamine (6-OHDA) infusions and treated for at
      least 28 days with vehicle or L-DOPA. In the first experiment, striatal,
      hippocampal, amygdalar, and prefrontal cortex DA and 5-HT levels were examined at
      various post-treatment time-points. In experiment 2, L-DOPA's effects on DA and 5
      HT cell bodies in the substantia nigra pars compacta and dorsal raphe,
      respectively, were examined. Finally, the effects of L-DOPA on affective
      behaviors were assessed in locomotor chambers, social interaction, forced swim,
      and elevated plus maze behavioral tests. Bilateral 6-OHDA lesion induced
      approximately 80% DA and 30% 5-HT depletion in the striatum compared to sham
      lesioned controls, while monoamine levels remained largely unchanged in
      extrastriatal regions. Tissue levels of DA were increased at the expense of 5-HT
      levels in parkinsonian rats subjected to chronic L-DOPA injections in all regions
      sampled, though DA or 5-HT cell bodies were unaffected. Behaviorally, rats could
      only be tested 24h after their last L-DOPA injection due to severe dyskinesia.
      Despite this, prior exposure to chronic L-DOPA treatment exerted a pronounced
      anxiogenic phenotype. Collectively, these results suggest that chronic L-DOPA
      treatment may interfere with the balance of DA and 5-HT function in affect
      related brain regions and could induce and/or exacerbate non-motor symptoms in
      PD.

PMID- 22659570
TI  - LPA-induced suppression of periostin in human osteosarcoma cells is mediated by
      the LPA(1)/Egr-1 axis.
AB  - Lysophosphatidic acid (LPA), a naturally occurring bioactive phospholipid,
      mediates a multitude of (patho)physiological events including activation of
      mitogen-activated protein kinases (MAPKs). As LPA may induce cellular reponses in
      human osteosarcoma, the present study aimed at investigating expression of
      various LPA receptors, LPA-mediated activation of MAPK via G-protein coupling,
      and expression of early response genes in a cellular model for human
      osteosarcoma. We show that MG-63 cells express three members of the endothelial
      differentiation gene (Edg) family of G-protein coupled receptor transcripts
      (LPA(1-3)) but only two (LPA(4/5)) out of three members of the non-Edg family LPA
      receptor transcripts. Stimulation of MG-63 cells with LPA or synthetic LPA
      receptor agonists resulted in p42/44 MAPK phosphorylation via LPA(1)-LPA(3)
      receptors. Using pharmacological inhibitors, we show that LPA-mediated
      phosphorylation of p42/44 MAPK by LPA receptor engagement is transmitted by
      G(alphai)-dependent pathways through the Src family of tyrosine kinases. As a
      consequence, a rapid and transient upregulation of the zinc finger transcription
      factor early growth response-1 (Egr-1) was observed. Egr-1 expression was
      strictly mediated via G(alphai)/Src/p42/44 MAPK pathway; no involvement of the
      G(alphaq/11)/PLC/PKC or the PLD/PI3 kinase/Akt pathways was found. LPA-induced
      expression of functional Egr-1 in MG-63 cells could be confirmed by
      electrophoretic mobility shift assay. LPA-induced Egr-1 upregulation was
      accompanied by a time-dependent decrease of periostin (previously called
      osteoblast-specific factor 2), a cell adhesion protein for pre-osteoblasts.
      Silencing of LPA(1) and/or Egr-1 in MG-63 cells reversed LPA-mediated suppression
      of periostin. We here demonstrate a crosslink between Egr-1 and periostin in
      cancer cells, in particular in human osteosarcoma.

PMID- 22659571
TI  - Characterization of a series of 4-aminoquinolines that stimulate caspase-7
      mediated cleavage of TDP-43 and inhibit its function.
AB  - Dysfunction of the heterogeneous ribonucleoprotein TAR DNA binding protein 43
      (TDP-43) is associated with neurodegeneration in diseases such as amyotrophic
      lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we
      examine the effects of a series of 4-aminoquinolines with affinity for TDP-43
      upon caspase-7-induced cleavage of TDP-43 and TDP-43 cellular function. These
      compounds were mixed inhibitors of biotinylated TG6 binding to TDP-43, binding to
      both free and occupied TDP-43. Incubation of TDP-43 and caspase-7 in the presence
      of these compounds stimulated caspase-7 mediated cleavage of TDP-43. This effect
      was antagonized by the oligonucleotide TG12, prevented by denaturing TDP-43, and
      exhibited a similar relation of structure to function as for the displacement of
      bt-TG6 binding to TDP-43. In addition, the compounds did not affect caspase-7
      enzyme activity. In human neuroglioma H4 cells, these compounds lowered levels of
      TDP-43 and increased TDP-43 C-terminal fragments via a caspase-dependent
      mechanism. Subsequent experiments demonstrated that this was due to induction of
      caspases 3 and 7 leading to increased PARP cleavage in H4 cells with similar rank
      order of the potency among the compounds tests for displacement of bt-TG6
      binding. Exposure to these compounds also reduced HDAC-6, ATG-7, and increased
      LC3B, consistent with the effects of TDP-43 siRNA described by other
      investigators. These data suggest that such compounds may be useful biochemical
      probes to further understand both the normal and pathological functions of TDP
      43, and its cleavage and metabolism promoted by caspases.

PMID- 22659572
TI  - DNA hypomethylation and oxidative stress-mediated increase in genomic instability
      in equine sarcoid-derived fibroblasts.
AB  - It is widely accepted that equine sarcoid disease, the most common skin
      associated neoplasm in equids, is induced by bovine papillomavirus (BPV-1).
      Although BPV-1 DNA has been found in almost all examined sarcoids so far, its
      detailed impact on the horse's host cell metabolism is largely unknown. We used
      equine fibroblast cell lines originating from sarcoid biopsies to study BPV-1
      associated changes on DNA methylation status and oxidative stress parameters.
      Sarcoid-derived fibroblasts manifested increased proliferation in vitro,
      transcriptional rDNA activity (NORs expression) and DNA hypomethylation compared
      to control cells. Cells isolated from equine sarcoids suffered from oxidative
      stress: the expression of antioxidant enzymes was decreased and the superoxide
      production was increased. Moreover, increased ploidy, oxidative DNA damage and
      micronuclei formation was monitored in sarcoid cells. We postulate that both
      altered DNA methylation status and redox milieu may affect genomic stability in
      BPV-1-infected cells and in turn contribute to sarcoid pathology.

PMID- 22659573
TI  - New insights into pb5, the receptor binding protein of bacteriophage T5, and its
      interaction with its Escherichia coli receptor FhuA.
AB  - The majority of bacterial viruses are bacteriophages bearing a tail that serves
      to recognise the bacterial surface and deliver the genome into the host cell.
      Infection is initiated by the irreversible interaction between the viral receptor
      binding protein (RBP) and a receptor at the surface of the bacterium. This
      interaction results ultimately in the phage DNA release in the host cytoplasm.
      Phage T5 infects Escherichia coli after binding of its RBP pb5 to the outer
      membrane ferrichrome transporter FhuA. Here, we have studied the complex formed
      by pb5 and FhuA by a variety of biophysical and biochemical techniques. We show
      that unlike RBPs of known structures, pb5 probably folds as a unique domain
      fulfilling both functions of binding to the host receptor and interaction with
      the rest of the phage. Pb5 likely binds to the domain occluding the beta-barrel
      of FhuA as well as to external loops of the barrel. Furthermore, upon binding to
      FhuA, pb5 undergoes conformational changes, at the secondary and tertiary
      structure level that would be the key to the transmission of the signal through
      the tail to the capsid, triggering DNA release. This is the first structural
      information regarding the binding of a RBP to a proteic receptor.

PMID- 22659574
TI  - Reconstructing the free-energy landscape associated to molecular motors
      processivity.
AB  - We propose a biochemical model providing the kinetic and energetic descriptions
      of the processivity dynamics of kinesin and dinein molecular motors. Our approach
      is a modified version of a well known model describing kinesin dynamics and
      considers the presence of a competitive inhibition reaction by ADP. We first
      reconstruct a continuous free-energy landscape of the cycle catalyst process that
      allows us to calculate the number of steps given by a single molecular motor.
      Then, we calculate an analytical expression associated to the translational
      velocity and the stopping time of the molecular motor in terms of time and ATP
      concentration. An energetic interpretation of motor processivity is discussed in
      quantitative form by using experimental data. We also predict a time duration of
      collective processes that agrees with experimental reports.

PMID- 22659575
TI  - Breath analysis science at PittCon 2012, Orlando, Florida.

PMID- 22659576
TI  - More chemicals show epigenetic effects across generations.

PMID- 22659577
TI  - Rapid urbanization as well as cultural habits explain the rise in heart disease
      in the Gulf States.
AB  - The European Society of Cardiology extends its scientific activities beyond
      Europe and into the emerging regions of the world.

PMID- 22659578
TI  - Effects of distinct collybistin isoforms on the formation of GABAergic synapses
      in hippocampal neurons.
AB  - Collybistin (Cb) is a brain specific guanine nucleotide exchange factor that
      interacts with the inhibitory postsynaptic scaffold protein gephyrin. Cb is
      essential for the postsynaptic clustering of gephyrin and major GABA(A) receptor
      subtypes during the formation and maintenance of GABAergic synapses in the
      hippocampus and other areas of the forebrain. In the rat, four distinct splice
      variants (Cb1, Cb2(SH3-), Cb2(SH3+) and Cb3), have been described, which differ
      in their C-termini (Cb1-3) and in respect of the SH3-domain that is absent in
      Cb2(SH3-). In the human brain, only a single isoform (hPEM2) corresponding to
      Cb3, was found to be expressed. This has been implicated in neurological defects
      such as hyperekplexia, epilepsy, anxiety, aggression and mental retardation. In
      this study, we address the functional significance of the differentially spliced
      Cb isoforms by generating a shRNA-mediated knock-down of endogenous Cb in
      hippocampal cultured neurons that is subsequently rescued by the expression of
      distinct Cb isoforms. We found that the Cb knock-down induced impairment in
      GABAergic neurotransmission could be rescued by the expression of any of the Cb
      isoforms, independent of their C-termini or the presence of the SH3-domain in the
      N-terminal region. Thus, the different Cb isoforms all confer basic
      functionality.

PMID- 22659579
TI  - The roles of omega-3 and omega-6 fatty acids in idiopathic male infertility.

PMID- 22659580
TI  - The CRF1 receptor antagonist SSR125543 attenuates long-term cognitive deficit
      induced by acute inescapable stress in mice, independently from the hypothalamic
      pituitary adrenal axis.
AB  - The selective antagonist at the CRF1 receptor, SSR125543, has been shown to
      produce anxiolytic-like effects in a number of animal models. The aim of the
      present study was to verify whether these effects are mediated by an action on
      the hypothalamic pituitary adrenal (HPA) axis. SSR125543 effects were evaluated
      in a mouse model of post-traumatic stress disorder. Animals received two
      unavoidable electric foot-shocks (1.5 mA/2 s). Two weeks later they were placed
      in the shock context and fecal and plasma corticosterone levels were measured by
      enzyme-immunoassay. Their cognitive performances were evaluated using the object
      recognition task following administration of SSR125543 at 3, 10 and 30 mg/kg or
      paroxetine at 20 mg/kg (i.p.), used as positive control. To assess the
      involvement of the HPA axis in the drug effects, a separate group of animals was
      subjected to the same procedure and drug regimen, but was treated with
      dexamethasone to blunt the HPA axis. Stressed mice had higher levels of
      corticosterone following re-exposure to the context and displayed impaired
      cognitive performance as compared to control animals. Corticosterone levels were
      normalized in stressed mice by SSR125543 and the cognitive deficit was
      significantly attenuated by SSR125543 and paroxetine, whether the HPA axis was
      blunted or not. These findings confirm that SSR125543 is able to attenuate the
      deleterious effects of stressful exposure. Importantly, the observation that
      these effects were still present in dexamethasone-treated mice indicates that
      this action does not necessarily involve pituitary-adrenal axis blockade, thereby
      suggesting that extra-pituitary CRF1 receptors may play a role in these effects.

PMID- 22659581
TI  - Microinjection of the 5-HT7 receptor antagonist SB-269970 into the rat brainstem
      and basal forebrain: site-dependent effects on REM sleep.
AB  - The effects of SB-269970, a selective 5-HT7 receptor antagonist, on spontaneous
      sleep were studied in adult rats implanted for chronic sleep recordings. The 5
      HT7 receptor ligand was microinjected into the horizontal limb of the diagonal
      band of Broca (HDB) and the laterodorsal tegmental nucleus (LDT) during the light
      period of the 12-h light/12-h dark cycle. For comparative purposes the compound
      was administered systemically and, in addition, injected directly into the dorsal
      raphe nucleus (DRN). Microinjection of SB-269970 into the HDB and the DRN induced
      a significant reduction of rapid-eye-movement sleep (REMS). Similar effects were
      observed after systemic administration of the 5-HT7 receptor antagonist. On the
      other hand, local infusion of the compound into the LDT provoked the opposite
      effect. It is proposed that the deactivation of GABAergic cells located in the
      HDB, DRN and LDT is responsible for the changes induced by SB-269970 on REM sleep
      values. It is suggested that the antidepressant effect of the 5-HT7 receptor
      antagonist could partly depend on the involvement of neuronal systems located in
      the DRN and the HDB.

PMID- 22659582
TI  - Similarity-based restoration of metrical information: different listening
      experiences result in different perceptual inferences.
AB  - How do perceivers apply knowledge to instances they have never experienced
      before? On one hand, listeners might use idealized representations that do not
      contain specific details. On the other, they might recognize and process
      information based on more detailed memory representations. The current study
      examined the latter possibility with respect to musical meter perception,
      previously thought to be computed based on highly-idealized (isochronous)
      internal representations. In six experiments, listeners heard sets of metrically
      ambiguous melodies. Each melody was played in a simultaneous musical context with
      unambiguous metrical cues (3/4 or 6/8). Cross-melody similarity was manipulated
      by pairing certain cues-timbre (musical instrument) and motif content (2-6-note
      patterns)-with each meter, or distributing cues across meters. After multiple
      exposures, listeners heard each melody without context, and judged metrical
      continuations (all Experiments) or familiarity (Experiments 5-6). Responses were
      assessed for "metrical restoration"-the tendency to make metrical judgments that
      fit the melody's previously-heard metrical context. Cross-melody similarity
      affected the presence and degree of metrical restoration, and timbre affected
      familiarity. Results suggest that metrical processing may be calculated based on
      fairly detailed representations rather than idealized isochronous pulses, and is
      dissociated somewhat from familiarity judgments. Implications for theories of
      meter perception are discussed.

PMID- 22659583
TI  - Evaluation of the antifibrotic effect of fenofibrate and rosiglitazone on
      bleomycin-induced pulmonary fibrosis in rats.
AB  - Idiopathic pulmonary fibrosis is the most prevalent chronic fibrosing lung
      disease. Peroxisome proliferator-activated receptors-gamma agonists provide
      potential therapy for fibrotic diseases of the lung. Peroxisome proliferator
      activated receptors-alpha agonists may be helpful in the treatment of lung
      inflammatory diseases, however their therapeutic potential on the "fibro
      proliferative" process and extracellular matrix accumulation in idiopathic
      pulmonary fibrosis has been less well studied. So, the present study was
      conducted to evaluate the anti-fibrotic effects of fenofibrate (peroxisome
      proliferator-activated receptors-alpha agonist) alone and in combination with
      rosiglitazone (peroxisome proliferator-activated receptors-gamma agonist) on lung
      injury induced by bleomycin administration. Oral administration of either
      rosiglitazone (5 mg/kg/d) or fenofibrate (100 mg/kg/d) for 14 days, attenuated
      the severity of bleomycin-induced lung injury and fibrosis through decreasing
      lung water contents, lung fibrotic grading, lung hydroxyproline contents and lung
      transforming growth factor-beta1 levels; with no significant difference between
      them. Combined low doses of rosiglitazone (1 mg/kg/d) and fenofibrate (30
      mg/kg/d) provided more benefits than full separate doses of each on the
      deleterious effects accompanied bleomycin administration. These findings
      suggested the potential use of peroxisome proliferator-activated receptors-alpha
      ligands as anti-fibrotic agents in lung fibrosis. Additionally, the concurrent
      administration of fenofibrate and rosiglitazone in low doses has synergistic
      effect and enhanced the beneficial effects afforded by either fenofibrate or
      rosiglitazone.

PMID- 22659584
TI  - Chlorogenic acid ameliorates brain damage and edema by inhibiting matrix
      metalloproteinase-2 and 9 in a rat model of focal cerebral ischemia.
AB  - Chlorogenic acid (CGA) has been reported to have various beneficial effects on
      the cardiovascular and central nervous systems. The purpose of the current study
      was to investigate whether CGA has protective effects against cerebral ischemia
      and whether these effects are due to modification of brain edema-related vascular
      factors. In a rat model of transient middle cerebral artery occlusion (MCAo, 2h
      of occlusion followed by 22 h of reperfusion), we measured infarct volume and
      performed behavioral test to evaluate the effects of CGA on brain damage and
      sensory-motor functional deficits. Brain water content and Evans blue
      extravasation were measured to evaluate brain edema and blood brain barrier (BBB)
      damage. Lipid peroxidation (LPO) and the expressions and activities of matrix
      metalloproteinase (MMP)-2 and MMP-9 were measured to investigate the mechanisms
      of action. Intraperitoneal injection of CGA (3, 10, and 30 mg/kg) at 0 h and 2h
      after MCAo dose-dependently reduced infarct volume and sensory-motor functional
      deficits. It also reduced brain water content and Evans blue extravasation.
      Mechanistically, CGA reduced LPO and MMPs expressions and activities. These
      results suggest that CGA reduces brain damage, BBB damage and brain edema by
      radical scavenging activity and the inhibitory effects on MMP-2 and MMP-9.

PMID- 22659586
TI  - Erythropoietin attenuates cardiopulmonary bypass-induced renal inflammatory
      injury by inhibiting nuclear factor-kappaB p65 expression.
AB  - Acute renal injury is one of the most frequent complications after
      cardiopulmonary bypass (CPB). This study was designed to evaluate the potential
      protective effect of erythropoietin (EPO) on CPB-induced renal injury in a rat
      model. Male Sprague-Dawley rats were randomly divided into three groups, sham
      operated group (sham), control CPB group (control), erythropoietin CPB group
      (EPO). Blood samples were collected at the beginning, at the end of CPB, and at
      0.5, 1, 2 and 24 h post-operation, and the kidneys were harvested 24 h
      postoperatively and observed by optical microscopy. Levels of serum creatinine
      (Cr) and blood urea nitrogen (BUN) were assayed. Tumor necrosis factor-alpha (TNF
      alpha), interleukin-1beta (IL-1beta) and interleukin-6(IL-6) levels in the renal
      tissues were evaluated by the method of enzyme linked immunosorbent assay
      (ELISA). Protein and mRNA levels of nuclear factor kappa B p65 (NF-kappaB p65),
      intercellular adhesion molecule-1 (ICAM-1) were also determined using western
      blot and real-time PCR respectively. Serum Cr and BUN levels as well as TNF
      alpha, IL-1beta and IL-6 levels in renal tissues in control group were
      significantly higher than those in the sham group. However, the levels of above
      biomarkers were markedly decreased in EPO group when comparing with control
      group. Furthermore, NF-kappaB p65, ICAM-1 protein and mRNA expression were
      significantly down-regulated in EPO group comparing with control group. In
      addition, microscopic examinations revealed that histological injury was
      alleviated when treated with EPO. The results indicated that EPO potently
      protected against CPB-induced acute renal injury and inhibited expression of NF
      kappaB p65 and inflammatory response.

PMID- 22659585
TI  - Morphine efficacy is altered in conditional HIV-1 Tat transgenic mice.
AB  - Opiate abuse reportedly can exaggerate complications of human immunodeficiency
      virus type-1 (HIV-1) infection in the central nervous system (CNS), while opiate
      drugs are often indicated in the treatment of HIV-1-related neuropathic pain.
      Despite this quandary, few studies have assessed the relationship between the
      duration or extent of HIV-1 infection and the intrinsic neurobehavioral
      responsiveness to opioids. To address this problem, doxycycline (DOX)-inducible
      HIV-Tat(1-86) transgenic mice were used as a model for HIV-1-associated
      neurocognitive disorders, which permitted the regulation of Tat exposure and
      duration. The effects of continuous Tat induction on the activity of morphine
      were examined at weekly intervals using standard behavioral assays for
      nociception and motor function. In the spinal cord, Tat mRNA levels did not
      increase until the second and third weeks following induction, which corresponded
      to a significant loss of morphine antinociception as assessed in the tail-flick
      test. Alternatively, in the striatum, sustained increases in Tat mRNA expression
      during the second week of induction coincided with significant decreases in
      rotarod performance and interactions with morphine. Importantly, the behavioral
      effects of morphine differed depending on the timing and location of Tat
      expression, with increases in Tat transcript levels in the spinal cord and
      striatum corresponding to significant alterations in morphine-dependent
      nociception and rotarod performance, respectively. Assuming Tat levels contribute
      to the clinical manifestations of HIV-1, the results suggest that regional
      differences in viral load and opioid phenotype might influence the nature and
      degree that opiate responsiveness is altered in HIV-1-infected individuals.

PMID- 22659587
TI  - K-134, a phosphodiesterase 3 inhibitor, improves gait disturbance and hindlimb
      blood flow impairment in rat peripheral artery disease models.
AB  - K-134, a phosphodiesterase 3 (PDE3) inhibitor with anti-thrombotic and anti
      hyperplastic activity, is being developed for the treatment of intermittent
      claudication. We assessed the efficacy of K-134 against gait disturbance in two
      rat experimental peripheral arterial disease (PAD) models: the bilateral laurate
      induced PAD model and femoral artery ligation model. In the laurate-induced
      peripheral arterial disease model, 1 week of repeated oral administration of K
      134 significantly improved gait disturbance. Cilostazol and clopidogrel did not
      significantly improve gait disturbance. Repeated oral administration of K-134 and
      cilostazol significantly improved gait disturbance in the femoral artery ligation
      model. We evaluated the effects of K-134 and cilostazol treatment on hindlimb
      blood flow pre- and post-treadmill exercise in this model by laser Doppler
      perfusion imaging. Both drugs increased hindlimb blood flow both pre- and post
      treadmill exercise after 1 week of treatment. After 4 weeks of drug treatment,
      without preceding drug administration which is supposed to exert acute effects on
      vessel walls, both drugs significantly increased hindlimb blood flow after
      exercise. Moreover, K-134 at 30 mg/kg significantly prolonged walking distance.
      These results suggest that K-134 may be useful for treating intermittent
      claudication.

PMID- 22659588
TI  - Differential patterns of neuronal activation in rostral versus caudal ventral
      tegmental area involved in behavioral sensitization induced by an escalating-dose
      morphine administration paradigm.
AB  - The transition to addiction often involves a gradual process of escalated drug
      intake. The purpose of the present study was to characterize neuronal activation
      in the ventral tegmental area (VTA) and substantia nigra (SN) following chronic
      escalating-dose morphine exposure (days 1-7, 2 mg/kg/d; days 8-21, beginning at
      10 mg/kg/d, increasing by 2 mg/kg/d), with steady-dose morphine (2 mg/kg/d, i.p.,
      for 21 days) as the comparison. Using immunohistochemical double-staining for
      tyrosine hydroxylase (TH) and Fos, we found that the number of Fos(+)TH(+)
      neurons in the rostral VTA and number of Fos(+)TH(-) neurons in the lateral SNr
      were significantly increased in escalating-dose morphine-treated rats compared
      with steady-dose morphine-treated rats and acute morphine-treated rats.
      Meanwhile, this increase was associated with robust expression of behavioral
      sensitization after a challenge with 10 mg/kg morphine. The number of Fos(+)TH(+)
      neurons was significantly increased by acute morphine in the caudal VTA and SNc,
      but this number did not increase further with morphine pretreatment. These
      results demonstrate that behavioral sensitization was associated with elevated
      activation of dopaminergic neurons in the rostral VTA and nondopaminergic neurons
      in the lateral SNr, which could only be induced by chronic escalating-dose
      morphine rather than chronic steady-dose morphine pretreatment.

PMID- 22659589
TI  - Evidence for multiple extra-striate mechanisms behind perception of visual motion
      gradients.
AB  - Perceiving motion patterns in visual scenes in which speed or motion direction
      varies over space while average luminance remains constant presents a processing
      task that requires at least two separate stages of neural spatio-temporal
      filtering. We have previously probed the transfer of information between these
      stages of filtering identifying a largely scale invariant process in which
      narrowband initial motion sensitive filters are coupled with a broad range of
      spatial frequencies of secondary filters, with an optimal coupling - in terms of
      optimal observer visual sensitivity - at a frequency ratio of around twelve. In
      the current work, we used the same stimulus to investigate the possible presence
      of multiple secondary filtering mechanisms and their associated bandwidths. Using
      a forced choice psychophysical task with both a detection and an identification
      component, we presented experimental blocks containing stimuli with one of two
      different modulator frequencies in each trial to measure the frequency difference
      at which the detection performance matched the identification of the frequency.
      We found that at a frequency differences of about 2.2 octaves, performance of
      both tasks was similar, and the processing could therefore be inferred to occur
      in independent frequency channels. The same observation was confirmed for stimuli
      presented at a longer viewing distance. We conclude that for the motion gradient
      stimuli, there are secondary filtering mechanisms with a moderately broad
      bandwidth of over 2 octaves that underlie our sensitivity for detecting motion
      gradients of different modulation frequency. These are likely to be implemented
      at least in part within the dorsal stream of extra-striate cortex.

PMID- 22659590
TI  - Refractory disseminated fusariosis by Fusarium verticillioides in a patient with
      acute myeloid leukaemia relapsed after allogeneic hematopoietic stem cell
      transplantation: a case report and literature review.
AB  - BACKGROUND: Fusarium species are among the leading fungal pathogens to cause
      invasive mould infections in patients with hematopoietic malignancy. The Fusarium
      species most frequently involved in human infections are Fusarium solani,
      Fusarium oxysporum and Fusarium verticillioides. However, identification is a
      cumbersome and time-consuming task. Fusarium is resistant in vitro to many of the
      antifungal agents and the management of fusariosis is not well defined.
      OBJECTIVES: To emphasise the difficulty of identifying Fusarium spp. by
      conventional methods and the need of new rapid molecular tests to achieve earlier
      diagnosis and appropriate therapy. METHODS: A disseminated Fusarium infection due
      to F. verticillioides was documented in a neutropenic refractory patient with
      acute myeloid leukaemia, relapsed after allogeneic hematopoietic stem cell
      transplantation. RESULTS: The patient died despite liposomal amphotericin B and
      voriconazole combination and "in vitro" susceptibility of agents employed.
      Morphological and molecular identification of F. verticillioides was obtained
      only after the death of the patient. CONCLUSIONS: This case highlights the poor
      outcome of an invasive fungal disease caused by Fusarium in aplastic patients.
      Identification of members of Fusarium genus remains restricted to selected
      laboratories and should be introduced into routine mycological diagnostics. In
      immunocompromised patients, diagnosis of fusariosis is directly related to prompt
      diagnosis and to patient's status. Current diagnosis methods and therapeutic
      options are discussed.

PMID- 22659591
TI  - Insonation of targeted microbubbles produces regions of reduced blood flow within
      tumor vasculature.
AB  - OBJECTIVES: In ultrasound molecular imaging, a sequence of high-pressure
      ultrasound pulses is frequently applied to destroy bound targeted microbubbles,
      to quantify accumulated microbubbles or to prepare for successive microbubble
      injections; however, the potential for biological effects from such a strategy
      has not been fully investigated. Here, we investigate the effect of high-pressure
      insonation of bound microbubbles and the potential for thrombogenic effects.
      MATERIALS AND METHODS: A total of 114 mice carrying either Met-1 or neu deletion
      mutant (NDL) tumors was insonified (Siemens Sequoia system, 15L8 transducer, 5
      MHz color-Doppler pulses, 4 or 2 MPa peak-negative pressure, 8.1-millisecond
      pulse repetition period, 6-cycle pulse length, and 900-millisecond insonation).
      Microbubbles conjugated with cyclic-arginine-glycine-aspartic acid (cRGD) or
      cyclic-aspartic-acid-glycine-tyrosine (3-NO)-glycine-hydroxyproline-asparagine
      (LXY-3) peptides or control (no peptide) microbubbles were injected, and contrast
      pulse sequencing was used to visualize the flowing and bound microbubbles. An
      anti-CD41 antibody was injected in a subset of animals to block potential
      thrombogenic effects. RESULTS: After the accumulation of targeted microbubbles
      and high-pressure (4 MPa) insonation, reduced blood flow, as demonstrated by a
      reduction in echoes from flowing microbubbles, was observed in 20 Met-1 mice
      (71%) and 4 NDL mice (40%). The area of low image intensity increased from 22 +/-
      13% to 63 +/- 17% of the observed plane in the Met-1 model (P < 0.01) and from 16
      +/- 3% to 45 +/- 24% in the NDL model (P < 0.05). Repeated microbubble
      destruction at 4 MPa increased the area of low image intensity to 76.7 +/- 13.4%
      (P < 0.05). The fragmentation of bound microbubbles with a lower peak-negative
      pressure (2 MPa) reduced the occurrence of the blood flow alteration to 28% (5/18
      Met-1 tumor mice). The persistence of the observed blood flow change was
      approximately 30 minutes after the microbubble destruction event. Dilated vessels
      and enhanced extravasation of 150 kDa fluorescein-isothiocyanate (FITC)-dextran
      were observed by histology and confocal microscopy. Preinjection of an anti-CD41
      antibody blocked the reduction of tumor blood flow, where a reduction in blood
      flow was observed in only 1 of 26 animals. CONCLUSION: High-pressure
      fragmentation of microbubbles bound to tumor endothelial receptors reduced blood
      flow within 2 syngeneic mouse tumor models for ~30 minutes. Platelet activation,
      likely resulting from the injury of small numbers of endothelial cells, was the
      apparent mechanism for the flow reduction.

PMID- 22659592
TI  - Normalized metal artifact reduction in head and neck computed tomography.
AB  - OBJECTIVE: Artifacts from dental hardware affect image quality and the
      visualization of lesions in the oral cavity and oropharynx in computed tomography
      (CT). Therefore, magnetic resonance imaging is considered the imaging modality of
      choice in this region. Standard methods for metal artifact reduction (MAR) in CT
      replace the metal-affected raw data by interpolation, which is prone to new
      artifacts. We developed a generalized normalization technique for MAR (NMAR) that
      aims to suppress algorithm-induced artifacts and validated the performance of
      this algorithm in a clinical trial. MATERIAL AND METHODS: A 3-dimensional forward
      projection identifies the metal-affected raw data in the original projections
      after metal is segmented in the image domain by thresholding. A prior image is
      used to normalize the projections before interpolation. The original raw data are
      divided pixel-wise by the projection data of the prior image and, after
      interpolation, are denormalized again. Data from 19 consecutive patients with
      metal artifacts from dental hardware were reconstructed with standard filtered
      backprojection (FBP), linear interpolation MAR (LIMAR), and NMAR. The image
      quality of slices containing metal was analyzed for the severity of artifacts and
      diagnostic value; magnetic resonance imaging performed the same day on a 3-T
      system served as a reference standard in all cases. RESULTS: A total of 260
      slices containing metal dental hardware were analyzed. A total of 164 slices were
      nondiagnostic with FBP, 157 slices with LIMAR, and 87 slices with NMAR. The mean
      (SD) number of slices per patient with severe artifacts was 10.1 (3.7), 9.6
      (4.6), and 5.4 (3.6) and the mean (SD) number of slices with artifacts affecting
      diagnostic confidence was 3.3 (1.7), 4.9 (2.9), and 3.7 (1.9) for FBP, LIMAR, and
      NMAR, respectively (P < 0.001). Pairwise comparison did not show significant
      differences between FBP and LIMAR (P = 0.40), but there were significant
      differences between FBP and NMAR as well as LIMAR and NMAR (both P < 0.001).
      Interobserver agreement was excellent (kappa = 0.974). Two malignant lesions were
      unmasked with NMAR image reconstructions. No algorithm-related artifacts were
      detected in regions that did not contain metal in NMAR images. CONCLUSION:
      Normalized MAR has the potential to improve image quality in patients with
      artifacts from dental hardware and to improve the diagnostic accuracy of CT of
      the oral cavity and oropharynx.

PMID- 22659593
TI  - Quantitative contrast-enhanced ultrasound for imaging antiangiogenic treatment
      response in experimental osteolytic breast cancer bone metastases.
AB  - OBJECTIVES: The aim of this study was to investigate the feasibility of using
      contrast-enhanced ultrasound (CEUS) in experimental breast cancer bone metastases
      and its utilization for assessment of early antiangiogenic treatment response in
      these lesions. MATERIALS AND METHODS: Nude rats bearing bone metastases (n = 20)
      were treated with the antiangiogenic tyrosine kinase inhibitor sunitinib daily
      from days 30 to 35 after MDA-MB-231 tumor cell inoculation (n = 10) and compared
      with sham-treated controls (n = 10). Imaging with ultrasound (US) and magnetic
      resonance imaging (MRI) was performed on days 30, 32, and 35 after tumor cell
      inoculation to determine tumor volume and parameters of vascularization in bone
      metastases. Contrast-enhanced US images were used to calculate wash-in and wash
      out values, peak enhancement, and area under the curve from time intensity
      curves. In addition, a quantitative analysis software was used to determine
      regional blood volume and flow as well as filling times within bone metastases.
      For comparison, dynamic contrast-enhanced MRI provided amplitude A and exchange
      rate constant kep, respectively. Immunohistological analysis of the vasculature
      in bone metastases followed in vivo imaging experiments. RESULTS: Although no
      changes in tumor volume were assessed in the observation time, significantly
      decreased values for peak enhancement, area under the curve, and wash-out were
      determined by CEUS in animals treated with sunitinib at day 35 after tumor cell
      inoculation. Analysis of CEUS images with quantitative analysis software showed
      significantly lower values for regional blood volume and regional blood flow as
      well as higher values for filling time in treated animals as early as 2 days
      after therapy onset. Dynamic contrast-enhanced MRI revealed significantly
      decreased values for parameter A at day 35 and kep at days 32 and 35 after tumor
      cell inoculation for treated animals. Immunohistology of bone metastases revealed
      significantly larger vessels and decreased positive area fraction for von
      Willebrand Factor in animals treated with sunitinib. CONCLUSION: Contrast
      enhanced US is feasible in experimental breast cancer bone metastases and depicts
      early antiangiogenic treatment response in advanced osteolytic lesions.

PMID- 22659594
TI  - Magnetic resonance diffusion tensor imaging for evaluation of histopathological
      changes in a rat model of diabetic nephropathy.
AB  - OBJECTIVES: The aim of this study was to investigate whether magnetic resonance
      (MR) diffusion tensor imaging (DTI) allows assessment of renal pathologies in a
      rat model of diabetic nephropathy. MATERIALS AND METHODS: Twenty-one male Sprague
      Dawley rats were divided into 3 groups: (1) untreated controls, (2) diabetes
      (DM), (3) diabetes with uninephrectomy (DM UNX) to accelerate renal impairment.
      Eight weeks after diabetes induction with streptozotocin, MR imaging was
      performed in a 1.5-T scanner using an 8-channel wrist coil. Morphological proton
      density images and echoplanar DTI were obtained (b = 0 and 300 s/mm, 6 diffusion
      directions). Renal apparent diffusion coefficient (ADC) and fractional anisotropy
      (FA) values were calculated for each of the different anatomical layers of the
      kidney. Imaging results, laboratory parameters of diabetic state and kidney
      function, and renal histopathological changes (glomerulosclerosis, tubular
      dilatation, and renal fibrosis) were compared between groups. Correlations
      between FA and histopathological changes were evaluated. RESULTS: All diabetic
      animals developed hyperglycemia and hypoinsulinemia. Uremia, albuminuria, and
      histopathological changes were most pronounced in DM UNX animals. Fractional
      anisotropy was significantly reduced in DM UNX animals in the cortex (CO) (0.167;
      confidence interval [CI], 0.151-0.184; P < 0.001), outer stripe of the outer
      medulla (OS) (0.254; CI, 0.225-0.283; P = 0.038), and inner medulla (IM) (0.459;
      CI, 0.395-0.523; P = 0.008) compared with control animals (CO, 0.251; CI, 0.224
      0.277; OS, 0.309; CI, 0.267-0.350; IM, 0.559; CI, 0.515-0.603). In DM-without-UNX
      animals, only cortical FA was significantly lower than in controls (P < 0.001).
      Between groups, ADC values were not different, except for cortical ADC, which was
      higher in DM UNX animals than in controls. Significant negative correlations were
      observed between the FA of different anatomical layers and the extent of
      glomerulosclerosis (CO, P = 0.003, r = -0.65; and OS, P = 0.022, r = -0.52),
      tubulointerstitial fibrosis (IM, P = 0.028, r = -0.50), and tubular dilatation
      (CO, P = 0.015, r = -0.55; and IM, P = 0.006, r = -0.61), respectively.
      CONCLUSIONS: Magnetic resonance DTI by reduction of FA identified renal
      pathologies of diabetic nephropathy such as glomerulosclerosis, interstitial
      fibrosis, and tubular damage. Representing different stages of disease, DM and DM
      UNX animals could be differentiated. Thus, MR DTI may be valuable for noninvasive
      detection and monitoring of renal pathology in patients with diabetes.

PMID- 22659595
TI  - Metal artifact reduction by dual-energy computed tomography using energetic
      extrapolation: a systematically optimized protocol.
AB  - OBJECTIVES: Energetic extrapolation is a promising strategy to reduce metal
      artifacts in dual-source computed tomography (DSCT). We performed this study to
      systematically optimize image acquisition parameters for this approach in a hip
      phantom and assess its value in a clinical study. MATERIALS AND METHODS: Titanium
      and steel hip prostheses were placed in a standard hip phantom and a water tank
      and scanned on a DSCT scanner. Tube spectra, tube current ratio, collimation,
      pitch, and rotation time were optimized in a stepwise process. Artifacts were
      quantified by measuring the standard deviation of the computed tomography density
      in a doughnut-shaped region of interest placed around the prosthesis. A total of
      22 adult individuals with metallic implants referred for computed tomography for
      a musculoskeletal indication were scanned using the optimized protocol. Degree of
      artifacts and diagnostic image quality were rated visually (0-10) and maximum
      streak intensity was measured. RESULTS: Sn140/100 kVp proved superior to Sn140/80
      kVp. There was a benefit for increasing tube current ratio from 1:1 to 3:1, but
      not beyond, in favor of the Sn140 kVp spectrum. Artifacts were less severe for a
      collimation of 32 * 0.6 mm as compared with 40 * 0.6 mm. A pitch of 0.5 at a
      rotation time of 0.5 seconds per rotation was preferable to other combinations
      with comparable scanning times. In the clinical study, increasing the
      extrapolated photon energy from 64 to 120 keV decreased the severity of artifacts
      from 8.0 to 2.0 (P < 0.001) and decreased streak intensity from 871 to 153 HU (P
      < 0.001). The median diagnostic image quality rating improved from 2.5 to 8.0 (P
      < 0.001). The median energy level visually perceived as optimal for diagnostic
      evaluation was 113 keV (range, 100-130 keV). CONCLUSIONS: Sn140/100 kVp with a
      tube current ratio of 3:1, a collimation of 32 * 0.6 mm, and extrapolated
      energies of 105 to 120 keV are optimal parameters for a dedicated DSCT protocol
      that effectively reduces metal artifacts by energetic extrapolation. The protocol
      effectively reduces metal artifacts in all types of metal implants. The optimized
      reconstructions yielded relevant additional findings.

PMID- 22659596
TI  - Current limitations of molecular magnetic resonance imaging for tumors as
      evaluated with high-relaxivity CD105-specific iron oxide nanoparticles.
AB  - OBJECTIVE: Tumor imaging via molecular magnetic resonance imaging (MRI) that uses
      specific superparamagnetic iron oxide particles (SPIOs) has been addressed in the
      literature several times in the last 20 years. To our knowledge, none of the
      reported approaches is currently used for routine clinical diagnostic evaluation,
      nor are any in clinical development. This raises questions as to whether SPIO
      enhanced molecular MRI is sensitive and specific enough for use in clinical
      practice. The aim of our preclinical study was to investigate the minimum
      requirements for obtaining sensitive molecular MRI for use in tumor evaluations
      under optimal conditions. The well-vascularized F9 teratocarcinoma tumor model,
      which exhibits high levels of the highly accessible target CD105 (endoglin), was
      used to compare the accumulation and visualization of target-specific SPIOs by
      MRI. MATERIAL AND METHODS: Superparamagnetic iron oxide particles were optimized
      in the following ways: (a) proton relaxivity was increased for higher imaging
      sensitivity, (b) a coating material was used for optimal loading density of the
      alphaCD105 antibody, and (c) binding activity to the target CD105 was increased.
      Binding activity and specificity were confirmed in vitro using enzyme-linked
      immunosorbent assay and in vivo using pharmacokinetic and biodistribution studies
      of 11 F9 teratoma-bearing mice together with micro-autoradiography. CD105 target
      expression was determined using immunohistochemistry and quantitative enzyme
      linked immunosorbent assay. The transverse relaxation rate R2* was quantified by
      3.0-T MRI in the tumors, kidneys, and muscles before and up to 60 minutes after
      injection in 11 mice. The use of [Fe]-labeled SPIOs for all in vivo experiments
      allowed for the direct correlation of the imaging results with SPIO accumulation.
      RESULTS: High-relaxivity alphaCD105-polyacrylic acid-SPIOs (r2 up to 440 L mmol
      Fe s) with strong binding activity accumulated specifically in tumors (1.4%
      injected dose/g) and kidneys (4.1% injected dose/g) in a manner dependent on the
      target concentration. The accumulation occurred within the first 3 minutes after
      injection. Visualization of specific SPIOs was accomplished with MRI. In contrast
      to the successful use of MRI in all examined kidneys (mean +/- SEM DeltaR2*, 61
      +/- 11 s), only 6 of 11 tumors (mean +/- SEM DeltaR2*, 15 +/- 7 s) showed a clear
      signal when compared with the control even though optimal conditions were used.
      CONCLUSION: The accumulation of CD105-specific SPIOs in F9 mouse teratomas was
      robust. However, visualization of the specifically accumulated SPIOs by MRI was
      not reliable because of its limited signal detection sensitivity. We postulate
      that it will be challenging to improve the imaging properties of targeted SPIOs
      further. Therefore, molecular MRI by targeted SPIOs is currently not suitable for
      clinical tumor imaging using routinely applicable sequences and field strength.

PMID- 22659597
TI  - Mutation analysis of cases of sudden unexplained death, 15 years after death:
      prompt genetic evaluation after resuscitation can save future lives.
AB  - INTRODUCTION: The aim of this study is to use genetic mutation analysis to
      determine the cause of sudden unexpected death in young (SUDY) persons with
      normal autopsy findings, and to provide relatives with an identified cardiac
      mutation with suitable cardiovascular prevention. METHODS: We performed mutation
      analysis on blood samples from first-degree relatives of 25 cases with normal
      autopsy findings identified in the national Swedish study of sudden cardiac death
      in 15- to 35-year-olds from 1992 to 1999. RESULTS: We found three families with
      long QT syndrome through mutation screening, and the mutations were verified in
      two of the deceased. Eight family members were found to be mutation carriers and
      have been provided with suitable cardiovascular prevention. Mutation screening
      also identified a number of common polymorphisms in the individuals screened.
      Clinical history revealed one family each with short QT syndrome and hypertrophic
      cardiomyopathy, respectively, but no mutations were found in the family members
      or in the deceased. Two SCDs each had occurred in two of the affected families.
      CONCLUSION: Cardiac/genetic evaluation of relatives long after SUDY can reveal a
      diagnosis in 5/25 (20%) of cases. Since DNA extraction of formalin fixed paraffin
      embedded samples is unreliable, it is important that blood or tissue samples be
      stored at autopsy of such cases. This can facilitate establishing a diagnosis and
      thereby save lives in the future.

PMID- 22659598
TI  - Emergency preparedness in the 21st century: training and preparation modules in
      virtual environments.
AB  - OBJECTIVES: To determine the feasibility of evidence-based design and use of low
      cost virtual world environments for preparation and training in multi-agency,
      multi-site, major incident response. METHODS: A prospective cohort feasibility
      study was carried out. One pre-hospital, and two in-hospital major incident
      scenarios, were created in an accessible virtual world environment. 23 pre
      hospital and hospital-based clinicians each took part in one of three linked
      major incident scenarios: a pre-hospital bomb blast site, focusing on the roles
      of the team leader and triage person; a blast casualty in a resuscitation room,
      focusing on the role of the trauma team leader; a hospital command and control
      scenario focusing on the role of the clinical major incident co-ordinator/silver
      commander. Participants supplied both quantitative and qualitative feedback.
      RESULTS: Using a systematic, evidence-based approach, three scenarios were
      successfully developed and tested using low-cost virtual worlds (Second Life and
      OpenSimulator). All scenarios were run to completion. 95% of participants
      expressed a desire to use virtual environments for future training and
      preparation. Pre-hospital responders felt that the immersive virtual environment
      enabled training in surroundings that would be inaccessible in real-life.
      CONCLUSIONS: The feasibility and face/content validity of using low-cost virtual
      worlds for multi-agency major incident simulation has been established. Major
      incident planners and trainers should explore utilising this technology as an
      adjunct to existing methodologies. Future work will involve development of robust
      assessment metrics.

PMID- 22659599
TI  - Osteoarthritis patients' perceptions of "appropriateness" for total joint
      replacement surgery.
AB  - OBJECTIVE: To understand patients' perspectives on 'appropriateness' for hip and
      knee total joint arthroplasty (TJA). METHODS: Focus groups were conducted,
      stratified by history of a previous TJA, in English-speaking men and women aged
      40+ years with moderate to severe hip and knee osteoarthritis. Participants
      discussed: their appropriateness for TJA; the ideal candidate; patients' role in
      TJA decision making; and the relationship between appropriateness and willingness
      to consider TJA. Participants self-completed a questionnaire assessing
      demographics, arthritis severity (Western Ontario McMaster University
      Osteoarthritis index - WOMAC), perceived TJA candidacy and willingness to
      consider TJA. Focus groups were audio-taped and transcribed verbatim. Content
      analysis was performed. RESULTS: Eleven focus groups were conducted with 58
      participants in total: mean age 72 years; 79% female; 25 (43%) with prior TJA;
      mean WOMAC summary score 43.1. Half reported willingness to consider TJA and 43%
      felt they were appropriate for TJA. Appropriateness was equated with candidacy
      for the procedure. Pain intensity and the ability to cope with pain were
      identified as the most important factors determining surgical candidacy, but felt
      to be inadequately evaluated by physicians. TJA appropriateness and willingness
      were felt to be distinct, yet related, concepts; those unwilling had stricter
      criteria about candidacy than those who were willing. CONCLUSIONS: Participants
      equated appropriateness for TJA with surgical candidacy. Patients' pain
      experience (intensity, impact on quality of life, ability to cope) was seen as
      most important in determining appropriateness, but felt to be inadequately
      evaluated currently. Enhanced patient-physician communication, possibly through
      use of patient decision aids, has potential to improve patient selection for TJA.

PMID- 22659600
TI  - Identification of the pathogenic pathways in osteoarthritic hip cartilage:
      commonality and discord between hip and knee OA.
AB  - OBJECTIVE: To define for the first time the transcriptomes of normal and end
      stage osteoarthritis (OA) hip cartilage. MATERIALS AND METHODS: RNA was isolated
      from cartilage within 2h of joint replacement surgery. Gene expression was
      analyzed using Agilent GeneSpring GX 11 following hybridization to Illumina Human
      HT-12 V3 microarrays. Real-time reverse-transcription polymerase chain reaction
      (RT-PCR) was used to validate the expression of six genes identified by
      microarray as differentially expressed. Gene Set Enrichment Analysis (GSEA) and
      Ingenuity Pathway Analysis (IPA) were used to investigate enriched functions or
      canonical pathways amongst differentially expressed genes respectively. RESULTS:
      In total we identified 998 differentially expressed genes (fold change >= +/-1.5,
      P-value <= 0.01) between neck of femur fracture (NOF) (n = 10) and OA hip (n = 9)
      patient cartilage. These differentially expressed genes were enriched within 71
      canonical pathways. A comparison between a comparable knee dataset(20) only
      identified 229 genes similarly differentially expressed although remarkably 34
      canonical pathways overlapped between experiments. CONCLUSIONS: This study is the
      first to report a comprehensive gene expression analysis of human hip OA
      cartilage compared to control (NOF) cartilage at the whole-genome level. Our
      differential gene expression dataset shows excellent correlation with similar
      defined studies using comparable tissue but reveals discord between hip and knee
      OA at the individual gene status but with commonality with regards the molecular
      pathways involved.

PMID- 22659602
TI  - DNA damage, discoordinated gene expression and cellular senescence in
      osteoarthritic chondrocytes.
AB  - OBJECTIVE: The initiation/progression factors of osteoarthritic (OA) cartilage
      degeneration and the involved biological mechanisms remain rather enigmatic. One
      core reason for this might be a cellular senescence-like phenotype of OA
      chondrocytes, which might show a fundamentally different behavior pattern
      unexpected from the biological mechanism established in young cells. DESIGN: This
      study was designed to investigate one core property of senescent cells, the
      heterogeneity of gene expression, in OA chondrocytes by double-labeling
      immunolocalization using two genes (vimentin, S-100 protein) as surrogates, which
      are constitutively expressed by (normal) chondrocytes. The level of genomic DNA
      damage in OA chondrocytes was compared to normal chondrocytes and in vitro
      experiments designed to demonstrate that stochastic genomic DNA damage is able to
      induce heterogeneity of gene expression in chondrocytes. RESULTS: We show a
      significantly increased heterogeneity of gene expression for vimentin and S-100
      protein as well as a significantly increased genomic DNA damage in the OA
      compared to normal chondrocytes, whereas no evidence of critical telomere
      shortening was found. In vitro experiments demonstrated that stochastic genomic
      DNA damage induced by increased oxidative or genotoxic stress is able to induce
      the heterogeneity in gene expression found in the OA cells in situ. CONCLUSIONS:
      Our results suggest that OA chondrocytes show a special form of age-related cell
      degeneration, "progressive/stress-induced senescence", progressing over time due
      to accumulated DNA damage and subsequent chaotic gene activation pattern. This
      promotes increased malfunctioning of the cells and finally the loss of their
      capacity to keep up cell and tissue homeostasis, i.e., prevent OA.

PMID- 22659603
TI  - Application of response surface methodology to optimize decolourization of dyes
      by the laccase-mediator system.
AB  - Response surface methodology (RSM) was applied to optimize the decolourization of
      3 dyes belonging to 3 dye families such as reactive black 5 (diazoic), indigo
      carmine (indigoid) and aniline blue (anthraquinonic). Crude laccase from Trametes
      trogii and the laccase-mediator 1-hydroxybenzotriazole (HBT) were used in this
      study. Box-Behnken design using RSM with six variables namely pH, temperature,
      enzyme concentration, HBT concentration, dye concentration and incubation time
      was used in this study to optimize significant correlation between the effects of
      these variables on the decolourization of reactive black 5 (RB5), indigo carmine
      (IC) and aniline blue (AB). The optimum of pH, temperature, laccase, HBT, RB5 and
      reaction time were 4.5, 0.5 U ml(-1), 0.5 mM, 100 mg ml(-1) and 150 min
      respectively, for a maximum decolourization of RB5 (about 92.92% +/- 7.21).
      Whereas, the optimum decolourization conditions of both IC (99.76% +/- 7.75) and
      AB (98.44% +/- 10) were: pH 4.5, temperature of 45  degrees C, enzyme
      concentration of 0.1 U ml(-1) and 0.5 U ml(-1), HBT concentration of 0.9 mM and
      0.5 mM, dye concentration of 60 mg l(-1) and reaction time of 150 and 90 min,
      respectively. The experimental values were in good agreement with the predicted
      ones and the models were highly significant, the correlation coefficient (R(2))
      being 0.864, 0.663 and 0.776 for RB5, IC and AB, respectively. In addition, when
      the kinetic parameters for the three dyes decolourization were calculated
      according to Hannes-Wolf plot, the following values were obtained: Km of 268.4,
      47.94 and 44.64 mg l(-1) then V(max) of 35.58, 10.43 and 9.23 mg l(-1) min for
      the RB5, IC and AB decolourizations by laccase, respectively.

PMID- 22659601
TI  - Clinical outcome of autologous chondrocyte implantation is correlated with
      infrared spectroscopic imaging-derived parameters.
AB  - OBJECTIVE: To investigate whether Fourier transform infrared imaging spectroscopy
      (FT-IRIS), a modality based on molecular vibrations, is a viable alternative to
      histology and immunohistochemistry (IHC) for assessment of tissue quality and
      patient clinical outcome. METHODS: Osteochondral biopsies were obtained from
      patients (9-65 months post-surgery) who underwent an autologous chondrocyte
      implantation (ACI) procedure to repair a cartilage defect (N = 14). The repair
      tissue was evaluated histologically by OsScore grading, for the presence of types
      I and II collagen by IHC, and for proteoglycan (PG) distribution and collagen
      quality parameters by FT-IRIS. Patient clinical outcome was assessed by the
      Lysholm score. RESULTS: Improvement in Lysholm score occurred in 79% of patients.
      IHC staining showed the presence of types I and II collagen in all samples, with
      a greater amount of collagen type II in the deep zone. The amount and location of
      immunostaining for type II collagen correlated to the FT-IRIS-derived parameters
      of relative PG content and collagen helical integrity. In addition, the
      improvement in Lysholm score post-ACI correlated positively with the OsScore,
      type II collagen (IHC score) and FT-IRIS-determined parameters. Regression models
      for the relation between improvement in Lysholm score and either OsScore, IHC
      area score or the FT-IRIS parameters all reached significance (p < 0.01).
      However, the FT-IRIS model was not significantly improved with inclusion of the
      OsScore and IHC score parameters. CONCLUSION: Demonstration of the correlation
      between FT-IRIS-derived molecular parameters of cartilage repair tissue and
      patient clinical outcome lays the groundwork for translation of this methodology
      to the clinical environment to aid in the management of cartilage disorders and
      their treatment.

PMID- 22659604
TI  - Assesment of PM10 pollution episodes in a ceramic cluster (NE Spain): proposal of
      a new quality index for PM10, As, Cd, Ni and Pb.
AB  - Environmental pollution control is one of the most important goals in pollution
      risk assessment today. In this sense, modern and precise tools that allow
      scientists to evaluate, quantify and predict air pollution are of particular
      interest. Monitoring atmospheric particulate matter is a challenge faced by the
      European Union. Specific rules on this subject are being developed (Directive
      2004/107/EC, Directive 2008/50/EC) in order to reduce the potential adverse
      effects on human health caused by air pollution. Air pollution has two sources:
      natural and anthropogenic. Contributions from natural sources can be assessed but
      cannot be controlled, while emissions from anthropogenic sources can be
      controlled; monitoring to reduce this latter type of pollution should therefore
      be carried out. In this paper, we describe an air quality evaluation in terms of
      levels of atmospheric particles (PM10), as outlined by European Union
      legislation, carried out in an industrialised Spanish coastal area over a five
      year period with the purpose of comparing these values with those of other areas
      in the Mediterranean Basin with different weather conditions from North of
      Europe. The study area is in the province of Castellon. This province is a
      strategic area in the frame work of European Union (EU) pollution control.
      Approximately 80% of European ceramic tiles and ceramic frit manufacturers are
      concentrated in two areas, forming the so-called "ceramics clusters"; ones in
      Modena (Italy) and the other in Castellon. In this kind of areas, there are a lot
      of air pollutants from this industry then it is difficult to fulfill de European
      limits of PM10 so it is necessary to control the air quality in them. The
      seasonal differences in the number of days in which pollutant level limits were
      exceeded were evaluated and the sources of contamination were identified. Air
      quality indexes for each pollutant have been established to determine easily and
      clearly the quality of air breathed. Furthermore, in accordance with Directive
      2008/50/EC, an Air Quality Plan is proposed to protect human health, and the
      environment as a whole, in the study area. General and specific corrective
      measures of main emission sources are provided. A strategy for air pollution
      management is thus presented.

PMID- 22659605
TI  - Accumulation of Sb, Pb, Cu, Zn and Cd by various plants species on two different
      relocated military shooting range soils.
AB  - Annually, more than 400 t Pb and 10 t Sb enter Swiss soils at some 2000 military
      shooting ranges. After the decommission of military shooting ranges, heavily
      contaminated soils (>2000 mg kg(-1) Pb) are landfilled or processed by soil
      washing, whereas for soils with less contamination, alternate strategies are
      sought. Although the use of military shooting ranges for grazing in Switzerland
      is common practice, no assessment has been done about the uptake of Sb in plants
      and its subsequent potential intake by grazing animals. We determined the uptake
      of Sb, Pb, Cu, Zn and Cd in the aboveground biomass of nine plant species growing
      on a calcareous (Chur) and a weakly acidic (Losone) military shooting range soil
      in order to assess if grazing would be safe to employ on decommissioned military
      shooting ranges. The two soils did not differ in their total concentrations of
      Cu, Zn, Sb and Cd, they differed however in the total concentration of Pb.
      Additionally, their physical and chemical properties were significantly
      different. The accumulation of Zn, Cu, Cd and Pb in the shoots of all nine plant
      species remained below the Swiss tolerance values for fodder plants (150 mg kg(
      1) Zn, 15-35 mg kg(-1) Cu, 40 mg kg(-1) Pb, and 1 mg kg(-1) Cd DW), with the only
      exception of Pb in Chenopodium album shoots which reached a concentration of 62
      mg kg(-1) DW. Antimony concentrations were 1.5-2.6-fold higher in plants growing
      on the calcareous soil than on the weakly acidic soil. Considering Cu, Zn, Pb, Sb
      and Cd, all plants, with the exception C. album, would be suitable for grazing on
      similar shooting range soils.

PMID- 22659606
TI  - Flexible molecular-scale electronic devices.
AB  - Flexible materials and devices could be exploited in light-emitting diodes,
      electronic circuits, memory devices, sensors, displays, solar cells and
      bioelectronic devices. Nanoscale elements such as thin films, nanowires,
      nanotubes and nanoparticles can also be incorporated into the active films of
      mechanically flexible devices. Large-area devices containing extremely thin films
      of molecular materials represent the ultimate scaling of flexible devices based
      on organic materials, but the influence of bending and twisting on the electrical
      and mechanical stability of such devices has never been examined. Here, we report
      the fabrication and characterization of two-terminal electronic devices based on
      self-assembled monolayers of alkyl or aromatic thiol molecules on flexible
      substrates. We find that the charge transport characteristics of the devices
      remain stable under severe bending conditions (radius <= 1 mm) and a large number
      of repetitive bending cycles (>=1,000). The devices also remain reliable in
      various bending configurations, including twisted and helical structures.

PMID- 22659607
TI  - Hybrid nanomaterials. Not just a pretty flower.
AB  - Combining copper(II) phosphate and proteins leads to the formation of hybrid
      nanostructures that are shaped like flowers and have enhanced catalytic activity
      and stability.

PMID- 22659608
TI  - Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA
      delivery.
AB  - Nanoparticles are used for delivering therapeutics into cells. However, size,
      shape, surface chemistry and the presentation of targeting ligands on the surface
      of nanoparticles can affect circulation half-life and biodistribution, cell
      specific internalization, excretion, toxicity and efficacy. A variety of
      materials have been explored for delivering small interfering RNAs (siRNAs)--a
      therapeutic agent that suppresses the expression of targeted genes. However,
      conventional delivery nanoparticles such as liposomes and polymeric systems are
      heterogeneous in size, composition and surface chemistry, and this can lead to
      suboptimal performance, a lack of tissue specificity and potential toxicity.
      Here, we show that self-assembled DNA tetrahedral nanoparticles with a well
      defined size can deliver siRNAs into cells and silence target genes in tumours.
      Monodisperse nanoparticles are prepared through the self-assembly of
      complementary DNA strands. Because the DNA strands are easily programmable, the
      size of the nanoparticles and the spatial orientation and density of cancer
      targeting ligands (such as peptides and folate) on the nanoparticle surface can
      be controlled precisely. We show that at least three folate molecules per
      nanoparticle are required for optimal delivery of the siRNAs into cells and, gene
      silencing occurs only when the ligands are in the appropriate spatial
      orientation. In vivo, these nanoparticles showed a longer blood circulation time
      (t(1/2) ~ 24.2 min) than the parent siRNA (t(1/2) ~ 6 min).

PMID- 22659609
TI  - Protein-inorganic hybrid nanoflowers.
AB  - Flower-shaped inorganic nanocrystals have been used for applications in catalysis
      and analytical science, but so far there have been no reports of 'nanoflowers'
      made of organic components. Here, we report a method for creating hybrid organic
      inorganic nanoflowers using copper (II) ions as the inorganic component and
      various proteins as the organic component. The protein molecules form complexes
      with the copper ions, and these complexes become nucleation sites for primary
      crystals of copper phosphate. Interaction between the protein and copper ions
      then leads to the growth of micrometre-sized particles that have nanoscale
      features and that are shaped like flower petals. When an enzyme is used as the
      protein component of the hybrid nanoflower, it exhibits enhanced enzymatic
      activity and stability compared with the free enzyme. This is attributed to the
      high surface area and confinement of the enzymes in the nanoflowers.

PMID- 22659610
TI  - Gene delivery: Designer DNA give RNAi more spine.

PMID- 22659611
TI  - Dual-gated bilayer graphene hot-electron bolometer.
AB  - Graphene is an attractive material for use in optical detectors because it
      absorbs light from mid-infrared to ultraviolet wavelengths with nearly equal
      strength. Graphene is particularly well suited for bolometers-devices that detect
      temperature-induced changes in electrical conductivity caused by the absorption
      of light-because its small electron heat capacity and weak electron-phonon
      coupling lead to large light-induced changes in electron temperature. Here, we
      demonstrate a hot-electron bolometer made of bilayer graphene that is dual-gated
      to create a tunable bandgap and electron-temperature-dependent conductivity. The
      bolometer exhibits a noise-equivalent power (33 fW Hz(-1/2) at 5 K) that is
      several times lower, and intrinsic speed (>1 GHz at 10 K) three to five orders of
      magnitude higher than commercial silicon bolometers and superconducting
      transition-edge sensors at similar temperatures.

PMID- 22659612
TI  - Titanium dioxide photocleans polluted air.

PMID- 22659613
TI  - AD gene 3-D: moving past single layer genetic information to map novel loci
      involved in Alzheimer's disease.
AB  - Over the past 5 years, there has been considerable advancement in the genetics of
      Alzheimer's disease. This review will provide an overview of the current state of
      the field for analysis of genetic variation and Alzheimer's disease. Highlighted
      in this review will be the results from some of the more conventional approaches,
      including linkage and association studies, as well as an overview of an alternate
      approach: eQTL analysis. The emphasis will be on taking genomics to the next
      level by applying additional datasets to truly create maps of a 3-dimensional
      Alzheimer's genome by including the downstream effects of risk variation.

PMID- 22659614
TI  - Adaptation of intracytoplasmic membranes to altered light intensity in
      Rhodobacter sphaeroides.
AB  - The model photosynthetic bacterium Rhodobacter sphaeroides uses a network of
      bacteriochlorophyll (BChl)-protein complexes embedded in spherical
      intracytoplasmic membranes (ICM) to collect and utilise solar energy. We studied
      the effects of high- and low-light growth conditions, where BChl levels increased
      approximately four-fold from 1.6*10(6) to 6.5*10(6) molecules per cell. Most of
      this extra pigment is accommodated in the proliferating ICM system, which
      increases from approximately 274 to 1468 vesicles per cell. Thus, 16*10(6)nm(2)
      of specialised membrane surface area is made available for harvesting and
      utilising solar energy compared to 3*10(6)nm(2) under high-light conditions.
      Membrane mapping using atomic force microscopy revealed closely packed dimeric
      and monomeric reaction centre-light harvesting 1-PufX (RC-LH1-PufX) complexes in
      high-light ICM with room only for small clusters of LH2, whereas extensive LH2
      only domains form during adaptation to low light, with the LH2/RC ratio
      increasing three-fold. The number of upper pigmented band (UPB) sites where
      membrane invagination is initiated hardly varied; 704 (5.8*10(5) BChls/cell) and
      829 (4.9*10(5) BChls/cell) UPB sites per cell were estimated under high- and low
      light conditions, respectively. Thus, the lower ICM content in high-light cells
      is a consequence of fewer ICM invaginations reaching maturity. Taking into
      account the relatively poor LH2-to-LH1 energy transfer in UPB membranes it is
      likely that high-light cells are relatively inefficient at energy trapping, but
      can grow well enough without the need to fully develop their photosynthetic
      membranes from the relatively inefficient UPB to highly efficient mature ICM.

PMID- 22659615
TI  - l-Lactate metabolism in HEP G2 cell mitochondria due to the l-lactate
      dehydrogenase determines the occurrence of the lactate/pyruvate shuttle and the
      appearance of oxaloacetate, malate and citrate outside mitochondria.
AB  - As part of an ongoing study of l-lactate metabolism both in normal and in cancer
      cells, we investigated whether and how l-lactate metabolism occurs in
      mitochondria of human hepatocellular carcinoma (Hep G2) cells. We found that Hep
      G2 cell mitochondria (Hep G2-M) possess an l-lactate dehydrogenase (ml-LDH)
      restricted to the inner mitochondrial compartments as shown by immunological
      analysis, confocal microscopy and by assaying ml-LDH activity in solubilized
      mitochondria. Cytosolic and mitochondrial l-LDHs were found to differ from one
      another in their saturation kinetics. Having shown that l-lactate itself can
      enter Hep G2 cells, we found that Hep G2-M swell in ammonium l-lactate, but not
      in ammonium pyruvate solutions, in a manner inhibited by mersalyl, this showing
      the occurrence of a carrier-mediated l-lactate transport in these mitochondria.
      Occurrence of the l-lactate/pyruvate shuttle and the appearance outside
      mitochondria of oxaloacetate, malate and citrate arising from l-lactate uptake
      and metabolism together with the low oxygen consumption and membrane potential
      generation are in favor of an anaplerotic role for l-LAC in Hep G2-M.

PMID- 22659616
TI  - Alkynyl-functionalised and linked bicyclo[1.1.1]pentanes of group 14.
AB  - We report the synthesis and properties of alkynyl-functionalised and -bridged
      bicyclo[1.1.1]pentane derivatives consisting of the heavier group 14 elements
      silicon and tin.

PMID- 22659617
TI  - The phenoloxidase activity and antibacterial function of a tyrosinase from
      scallop Chlamys farreri.
AB  - Tyrosinase (TYR), also known as monophenol monooxygenase, is a ubiquitous
      binuclear copper-containing enzyme which catalyzes the hydroxylation of phenols
      to catechols and the oxidation of catechols to quinones. In the present study,
      the cDNA of a tyrosinase (CfTYR) was identified from scallop Chlamys farreri,
      which encoded a polypeptide of 486 amino acids. The CfTYR mRNA transcripts were
      expressed in all the tested tissues, including haemocytes, adductor muscle,
      kidney, hepatopancreas, gill, gonad and mantle, with the highest level in mantle.
      The expression level of CfTYR mRNA in haemocytes decreased significantly during 3
      6 h after LPS stimulation, and reached the lowest level at 6 h (0.05-fold, P <
      0.05). Then, it began to increase at 12 h (0.32-fold, P > 0.05), and reached the
      highest level at 24 h (2.91-fold, P < 0.05). At 3 h after LPS stimulation, the
      phenoloxidase activity catalyzing L-dopa and dopamine in haemolymph increased
      significantly to 53.13 and 40.36 U mg(-1) respectively, but it decreased to 10.82
      U mg(-1) and even undetectable level after CfTYR activity was inhibited.
      Furthermore, the antibacterial activity of haemolymph against Escherichia coli
      was also increased significantly at 3 h after LPS stimulation, but it decreased
      significantly when the haemolymph was treated by TYR inhibitor. The recombinant
      protein of the mature CfTYR peptide expressed in the in vitro Glycoprotein
      Expression Kit displayed phenoloxidase activity of 64.36 +/- 5.51 U mg(-1) in the
      present of trypsinase and Cu(2+). These results collectively suggested that CfTYR
      was a homologue of tyrosinase in scallop C. farreri with the copper-dependence
      phenoloxidase activity, and it could be induced after immune stimulation and
      mediate immune response for the elimination of invasive pathogens in scallop.

PMID- 22659618
TI  - Effects of Bacillus subtilis on the growth performance, digestive enzymes, immune
      gene expression and disease resistance of white shrimp, Litopenaeus vannamei.
AB  - We studied the effect of two probiotic Bacillus subtilis strains on the growth
      performance, digestive enzyme activity, immune gene expression and disease
      resistance of juvenile white shrimp (Litopenaeus vannamei). A mixture of two
      probiotic strains, L10 and G1 in equal proportions, was administered at two
      different doses 10(5) (BM5) and 10(8) (BM8) CFU g(-1) feed to shrimp for eight
      weeks. In comparison to untreated control group, final weight, weight gain and
      digestive enzyme activity were significantly greater in shrimp fed BM5 and BM8
      diets. Significant differences for specific growth rate (SGR) and survival were
      recorded in shrimp fed BM8 diet as compared with the control; however, no
      significant differences were recorded for food conversion ratio (FCR) among all
      the experimental groups. Eight weeks after the start of the feeding period,
      shrimp were challenged with Vibrio harveyi. Statistical analysis revealed
      significant differences in shrimp survival between probiotic and control groups.
      Cumulative mortality of the control group was 63.3%, whereas cumulative mortality
      of the shrimp that had been given probiotics was 20.0% with BM8 and 33.3% with
      BM5. Subsequently, real-time PCR was employed to determine the mRNA levels of
      prophenoloxidase (proPO), peroxinectin (PE), lipopolysaccharide- and beta-1,3
      glucan-binding protein (LGBP) and serine protein (SP). The expression of all
      immune-related genes studied was significantly up-regulated (P < 0.05) in the
      shrimp fed BM5 and BM8 diets compared to the control group. These findings
      demonstrate that administration of B. subtilis strains, L10 and G1, can improve
      growth performance and disease resistance through an enhanced immune response in
      shrimp.

PMID- 22659619
TI  - Sex differences in impaling behaviour of Great Grey Shrike Lanius excubitor: do
      males have better impaling skills than females?
AB  - Prey impaling in shrikes Laniidae is considered to be a feeding adaptation to
      dismember and consume large prey and is unique among food-storing animals.
      However, other exaptations of this behaviour were recorded, including signals in
      mate choice, where cache size is a sign of male quality. Thus, due to a strong
      sexual selection, male and female birds might differ in their behavioural
      patterns of impaling behaviour. We examined sex differences in impaling behaviour
      of the Great Grey Shrike Lanius excubitor - one of the species where caches are
      known to be sexual signals. Data were collected in western Poland during breeding
      seasons in the years 2006-2010. In the studied population, we recorded several
      sex-specific differences in impaling behaviour. Males impaled prey, invertebrates
      as well as vertebrates, faster and with fewer attempts per impaling event than
      females. Sexes differed in the location of impaled prey; males selected more
      visible places, especially during the mating and courtship phase, whereas females
      impaled prey in concealed locations. Males also had slightly better impaling
      success compared to females. We suggest that sex differences in impaling
      behaviour may be due to different uses of impaled prey, and the better impaling
      skills of males may be the result of better experience in impaling which is
      forced by sexual selection in this species. We also discuss other factors which
      might trigger sex-specific differences in food caching by shrikes.

PMID- 22659620
TI  - Targeting the glucagon receptor family for diabetes and obesity therapy.
AB  - Diabetes is a debilitating disease characterized by chronic hyperglycemia and is
      often associated with obesity. With diabetes and obesity incidence on the rise,
      it is imperative to develop novel therapeutics that will not only lower blood
      glucose levels, but also combat the associated obesity. The G protein-coupled
      receptors (GPCRs) for glucose-dependent insulinotropic polypeptide (GIP),
      glucagon-like peptide-1 (GLP-1) and glucagon are emerging as targets to treat
      both hyperglycemia and obesity. GIP is rapidly released from intestinal K-cells
      following food intake and stimulates glucose-dependent insulin secretion from
      beta-cells and the storage of fat in adipocytes. Both GIP receptor agonists and
      antagonists have been demonstrated to display therapeutic potential to treat
      diabetes and obesity. Similar to GIP, GLP-1 is released from intestinal L-cells
      following food intake and potentiates glucose-dependent insulin secretion from
      beta-cells. In addition, GLP-1 reduces glucagon levels, suppresses gastric
      emptying and reduces food intake. As such, GLP-1 receptor agonists effectively
      lower blood glucose levels and reduce weight. Finally, glucagon is released from
      alpha-cells and raises blood glucose levels during the fasting state by
      stimulating gluconeogenesis and glycogenolysis in the liver. Thus, molecules that
      antagonize the glucagon receptor may be used to treat hyperglycemia. Given the
      structural similarity of these peptides and their receptors, molecules capable of
      agonizing or antagonizing combinations of these receptors have recently been
      suggested as even better therapeutics. Here we review the biology of GIP, GLP-1
      and glucagon and examine the various therapeutic strategies to activate and
      antagonize the receptors of these peptides.

PMID- 22659621
TI  - Modulation of proximal signaling in normal and transformed B cells by
      transmembrane adapter Cbp/PAG.
AB  - The transmembrane protein Cbp/PAG (Csk binding protein/phospho-protein associated
      with glycosphingolipid-enriched microdomains) has a negative regulatory role in T
      cell activation as an adapter for C-terminal Src kinase, Csk. In T cells,
      membrane docking of Csk is promoted by binding to FynT-phosphorylated Cbp/PAG
      (pTyr317) to allow targeting of substrates residing in lipid rafts. Here, we
      investigate a potential parallel position for Cbp/PAG and the Src kinase Lyn in
      early B cell receptor signaling. Using normal and transformed B cells, we have
      compared signal profiles of BCR-triggered responses created by phospho-specific
      flow cytometry. In human normal B cells, our data show that reduced Cbp/PAG
      levels leads to enhanced and prolonged activation of proximal signaling
      mediators, while over-expression of the adapter in normal, EBV-transformed cells
      results in reduced calcium flux. Taken together, our findings support a negative
      regulatory function for Cbp/PAG in proximal BCR signaling in these cells.

PMID- 22659622
TI  - YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway.
AB  - Tight regulation of cell numbers by controlling cell proliferation and apoptosis
      is important during development. Recently, the Hippo pathway has been shown to
      regulate tissue growth and organ size in Drosophila. In mammalian cells, it also
      affects cell proliferation and differentiation in various tissues, including the
      nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and
      Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal
      differentiation. However, it remains unclear whether the Hippo pathway
      coordinates with other signaling cascades in regulating neuronal differentiation.
      Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model to
      study roles of YAP, a core component of the Hippo pathway, in neuronal
      differentiation. P19 cells can be induced to differentiate into neurons by
      expressing a neural bHLH transcription factor gene Ascl1. Our results showed that
      YAP promoted cell proliferation and inhibited neuronal differentiation.
      Expression of Yap activated Shh but not Wnt or Notch signaling activity during
      neuronal differentiation. Furthermore, expression of Yap increased the expression
      of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown
      of Gli2, a transcription factor of the Shh pathway, promoted neuronal
      differentiation even when Yap was over-expressed. We further demonstrated that
      over-expression of Yap inhibited neuronal differentiation in primary mouse
      cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap
      over-expressing cells. In conclusion, our study reveals that Shh signaling acts
      downstream of YAP in regulating neuronal differentiation.

PMID- 22659623
TI  - The mineralocorticoid receptor-p38MAPK-NFkappaB or ERK-Sp1 signal pathways
      mediate aldosterone-stimulated inflammatory and profibrotic responses in rat
      vascular smooth muscle cells.
AB  - AIM: To explore the signalling pathways involved in aldosterone-induced
      inflammation and fibrosis in rat vascular smooth muscle cells (VSMCs). METHODS:
      Using Western blotting and real-time RT-PCR, we investigated the effects of
      aldosterone on the expression of cyclooxygenase-2 (Cox-2) and IL-6, two important
      proinflammatory factors, and TGFbeta1, a critical profibrotic factor, in VSMCs.
      RESULTS: Aldosterone treatment significantly increased the expression of Cox-2
      and IL-6 and activation of p38MAPK and NF-kappaB. The expression of both Cox-2
      and IL-6 could be blocked by the mineralocorticoid receptor (MR) antagonist
      spironolactone and the p38MAPK inhibitor SB203580. Also, the rapid
      phosphorylation of p38MAPK could be suppressed by SB203580 but not by
      spironolactone, implicating in nongenomic effects of aldosterone. Similar to
      SB203580 and spironolactone, the NF-kappaB inhibitor alpha-p-tosyl-L-lysine
      chloromethyl ketone (TLCK) markedly attenuated expression of Cox-2, indicating
      that MR, p38MAPK and NF-kappaB are associated with aldosterone-induced
      inflammatory responses. Furthermore, aldosterone enhanced expression of TGFbeta1
      in rat VSMCs. This result may be related to activation of the MR/ERK-Sp1
      signalling pathway because PD98059, an ERK1/2 inhibitor, significantly blocked
      the rapid phosphorylation of ERK1/2 and function of Sp1 and led to reduced
      expression of TGFbeta1. Spironolactone was also shown to significantly inhibit
      TGFbeta1 and Sp1 expression but not ERK1/2 phosphorylation. CONCLUSION: These
      results suggest that aldosterone-induced inflammatory responses and fibrotic
      responses may be mediated by the MR/p38MAPK-NF-kappaB pathways and the MR/ERK-Sp1
      pathways in VSMCs, respectively.

PMID- 22659624
TI  - Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy
      Chinese volunteers.
AB  - AIM: To investigate the population pharmacokinetics (PK) and pharmacodynamics
      (PD) of bivalirudin, a synthetic bivalent direct thrombin inhibitor, in young
      healthy Chinese subjects. METHODS: Thirty-six young healthy volunteers were
      randomly assigned into 4 groups received bivalirudin 0.5 mg/kg, 0.75 mg/kg, and
      1.05 mg/kg intravenous bolus, 0.75 mg/kg intravenous bolus followed by 1.75 mg/kg
      intravenous infusion per hour for 4 h. Blood samples were collected to measure
      bivalirudin plasma concentration and activated clotting time (ACT). Population PK
      PD analysis was performed using the nonlinear mixed-effects model software
      NONMEM. The final models were validated with bootstrap and prediction-corrected
      visual predictive check (pcVPC) approaches. RESULTS: The final PK model was a two
      compartment model without covariates. The typical PK population values of
      clearance (CL), apparent distribution volume of the central-compartment (V(1)),
      inter-compartmental clearance (Q) and apparent distribution volume of the
      peripheral compartment (V(2)) were 0.323 L.h(-1).kg(-1), 0.086 L/kg, 0.0957 L.h(
      1).kg(-1), and 0.0554 L/kg, respectively. The inter-individual variabilities of
      these parameters were 14.8%, 24.2%, fixed to 0% and 15.6%, respectively. The
      final PK-PD model was a sigmoid E(max) model without the Hill coefficient. In
      this model, a covariate, red blood cell count (RBC(*)), had a significant effect
      on the EC(50) value. The typical PD population values of maximum effect (E(max)),
      EC(50), baseline ACT value (E(0)) and the coefficient of RBC(*) on EC(50) were
      318 s, 2.44 mg/L, 134 s and 1.70, respectively. The inter-individual
      variabilities of E(max), EC(50), and E(0) were 6.80%, 46.4%, and 4.10%,
      respectively. CONCLUSION: Population PK-PD models of bivalirudin in healthy young
      Chinese subjects have been developed, which may provide a reference for future
      use of bivalirudin in China.

PMID- 22659625
TI  - siRNA against plasminogen activator inhibitor-1 ameliorates bleomycin-induced
      lung fibrosis in rats.
AB  - AIM: Plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of
      pulmonary fibrosis. The present study was undertaken to examine the effects on
      pulmonary fibrosis of silencing PAI-1 expression with small interfering RNA
      (siRNA) and to assess the possible underlying mechanisms. METHODS: Male Wistar
      rats were subjected to intratracheal injection of bleomycin (BLM, 5 mg/kg, 0.2
      mL) to induce pulmonary fibrosis. Histopathological changes of lung tissue were
      examined with HE or Masson's trichrome staining. The expression levels of alpha
      smooth muscle actin (alpha-SMA), collagen type-I and type-III, caspase-3, as well
      as p-ERK1/2 and PI3K/Akt in the lung tissue were evaluated using
      imunohistochemistry and Western blot analyses. The fibroblasts isolated from BLM
      induced fibrotic lung tissue were cultured and transfected with pcDNA-PAI-1 or
      PAI-1siRNA. The expression level of PAI-1 in the fibroblasts was measured using
      real time RT-PCR and Western blot analysis. The fibroblast proliferation was
      evaluated using MTT assay. RESULTS: Intratracheal injection of PAI-1-siRNA (7.5
      nmoL/0.2 mL) significantly alleviated alveolitis and collagen deposition, reduced
      the expression of PAI-1, alpha-SMA, collagen type-I and collagen type-III, and
      increased the expression of caspase-3 in BLM-induced fibrotic lung tissue. In
      consistence with the in vivo results, the proliferation of the cultured
      fibroblasts from BLM-induced fibrotic lung tissue was inhibited by transfection
      with PAI-1-siRNA, and accelerated by overexpression of PAI-1 by transfection with
      pcDNA-PAI-1. The expression of caspase-3 was increased as a result of PAI-1 siRNA
      transfection, and decreased after transfection with pcDNA-PAI-1. In addition, the
      levels of p-ERK1/2 and PI3K/Akt in the fibrogenic lung tissue were reduced after
      treatment with PAI-1siRNA. CONCLUSION: The data demonstrate that PAI-1 siRNA
      inhibits alveolitis and pulmonary fibrosis in BLM-treated rats via inhibiting the
      proliferation and promoting the apoptosis of fibroblasts. Suppression ERK and AKT
      signalling pathways might have at least partly contributed to this process.
      Targeting PAI-1 is a promising therapeutic strategy for pulmonary fibrosis.

PMID- 22659626
TI  - Pharmacokinetic/pharmacodynamic studies on exenatide in diabetic rats.
AB  - AIM: To quantitatively evaluate the blood glucose-lowering effect of exenatide in
      diabetic rats. METHODS: Male Harlan-Sprague-Dawley rats were treated with high
      fat diet/streptozotocin to induce type 2 diabetes. After subcutaneous
      administration of a single dose of exenatide (4.2, 42, or 210 MUg/kg), serum
      exenatide, insulin concentration and blood glucose were measured. The
      pharmacokinetics of exenatide was characterized by a two-compartment model with
      first-order absorption. Insulin turnover was characterized by an effect
      compartment and indirect response combined model. Glucose turnover was described
      using an indirect response model with insulin (in effect compartment) stimulating
      glucose disposition and insulin (in insulin compartment) inhibiting glucose
      production simultaneously. The model parameters were estimated using nonlinear
      mixed-effects model program. Visual predictive check and model evaluation were
      used to make assessments. RESULTS: Exenatide exhibited rapid absorption with
      k(a)=4.45 h(-1), and the two-compartment model well described its pharmacokinetic
      profile. For the pharmacodynamic model, exenatide increased insulin release with
      the estimated S(m1) of 0.822 and SC(50) of 4.02 MUg/L. It was demonstrated that
      insulin stimulated glucose dissipation (S(m2)=0.0513) and inhibited the
      production of glucose (I(m)=0.0381). Visual predictive check and model evaluation
      study indicated that a credible model was developed. CONCLUSION: The glucose
      lowering effect of exenatide in diabetic rats is reliably described and predicted
      by the combined effect compartment/indirect response model.

PMID- 22659628
TI  - Extraskeletal osteosarcoma: a case report.
AB  - Extraskeletal osteosarcoma is a rare soft tissue sarcoma. Survival is related
      with the wide resection of the tumor. The role of adjuvant chemotherapy and
      radiation therapy remains controversial. In our study, we present a patient with
      extraskeletal osteosarcoma of the thigh which was initially misdiagnosed as
      lipoma.

PMID- 22659627
TI  - Phosphorylation of endothelial NOS contributes to simvastatin protection against
      myocardial no-reflow and infarction in reperfused swine hearts: partially via the
      PKA signaling pathway.
AB  - AIM: The cholesterol-lowering drugs statins could enhance the activities of
      endothelial nitric oxide synthase (eNOS) and protect myocardium during ischemia
      and reperfusion. The aim of this study was to examine whether protein kinase A
      (PKA) was involved in statin-mediated eNOS phosphorylation and cardioprotection.
      METHODS: 6-Month-old Chinese minipigs (20-30 kg) underwent a 1.5-h occlusion and
      3-h reperfusion of the left anterior descending coronary artery (LAD). In the
      sham group, the LAD was encircled by a suture but not occluded. Hemodynamic and
      cardiac function was monitored using a polygraph. Plasma activity of creatine
      kinase and the tissue activities of PKA and NOS were measured
      spectrophotometrically. p-CREB, eNOS and p-eNOS levels were detected using
      Western blotting. Sizes of the area at risk, the area of no-reflow and the area
      of necrosis were measured morphologically. RESULTS: Pretreatment of the animals
      with simvastatin (SIM, 2 mg/kg, po) before reperfusion significantly decreased
      the plasma activity of creatine kinase, an index of myocardial necrosis, and
      reduced the no-reflow size (from 50.4%+/-2.4% to 36.1%+/-2.1%, P<0.01) and the
      infarct size (from 79.0%+/-2.7% to 64.1%+/-4.5%, P<0.01). SIM significantly
      increased the activities of PKA and constitutive NOS, and increased Ser(133) p
      CREB protein, Ser(1179) p-eNOS, and Ser(635) p-eNOS in ischemic myocardium.
      Intravenous infusion of the PKA inhibitor H-89 (1 MUg.kg(-1).min(-1)) partially
      abrogated the SIM-induced cardioprotection and eNOS phosphorylation. In contrast,
      intravenous infusion of the eNOS inhibitor L-NNA (10 mg.kg(-1)) completely
      abrogated the SIM-induced cardioprotection and eNOS phosphorylation during
      ischemia and reperfusion, but did not affect the activity of PKA. CONCLUSION:
      Pretreatment with a single dose of SIM 2.5 h before reperfusion attenuates
      myocardial no-reflow and infarction through increasing eNOS phosphorylation at
      Ser(1179) and Ser(635) that was partially mediated via the PKA signaling pathway.

PMID- 22659629
TI  - Reconstruction of humeral diaphyseal non-unions with vascularized fibular graft.
AB  - OBJECTIVE: The aim of this study was to review the results of 5 diaphyseal non
      unions reconstructed using vascularized fibular grafts. METHODS: This study
      included six non-unions (3 males and 3 females; average age: 47 years; range: 21
      to 57 years) reconstructed using vascularized fibular grafts between 2002 and
      2007. Average duration of non-union was 59 (range: 12 to 156) months. Fixation
      was achieved with intramedullary nailing in 3 patients and plates in 3. One case
      was lost to follow-up at the third postoperative month. The remaining five
      patients were followed up for an average of 37 (range: 12 to 53) months. RESULTS:
      In four cases, union was achieved with a single operation at an average of 4.4
      months. A secondary intervention for grafting was required for one patient for
      inadequate consolidation of the proximal bone-graft interface. Mean radiographic
      humeral length difference was 3.6 (range: 1 to 7) cm. Average elbow range of
      motion was 130 (range: 100 to 145), shoulder flexion 167.5 (range: 165 to 170),
      shoulder abduction 172.5 (range: 170 to 180), internal rotation 75 (range: 70 to
      80), and external rotation 92.5 (range: 80 to 100) degrees. Mean DASH score was
      10 (range: 5 to 19). According to the Tang system, 3 patients had excellent and 2
      good clinical evaluations. Radiologic evaluation revealed four excellent and one
      fair result. No donor site morbidity was detected. CONCLUSION: Our results
      suggest that vascularized fibular grafting is an effective treatment option for
      the reconstruction of humeral diaphyseal non-unions.

PMID- 22659630
TI  - Minimally invasive plate osteosynthesis (MIPO) in diaphyseal humerus and proximal
      humerus fractures.
AB  - OBJECTIVE: Our aim was to evaluate the results of minimally invasive plate
      osteosynthesis (MIPO) using locking plates in diaphyseal humerus and proximal
      humerus fractures. METHODS: Nine patients who underwent open reduction and MIPO
      for the treatment of diaphyseal and proximal humerus fractures between June 2006
      and October 2009 were included in this study. One S3((r)) and 8 PHILOS((r))
      plates were used. Mean age was 75.2 (range: 32 to 86) years and all patients were
      females. Mean follow-up was 33.9 (range: 14.8 to 54.8) months. According to
      AO/ASIF classification, four patients had 12C1, two patients 12A1, one patient
      12A2, and two patients 11A2 fractures. Axillary and radial nerves were explored
      and protected in all patients. Patients were evaluated radiographically for union
      and functionally using the Constant-Murley score. RESULTS: None of the patients
      had nonunion, avascular necrosis, axillary or radial nerve paralysis or implant
      failure. Mean Constant-Murley score was 86.8 +/- 2.2 (range: 70 to 100). Mean
      union time was 3.2 (range: 2.5 to 5) months. CONCLUSION: MIPO of humerus
      diaphysis and proximal fractures allows for preservation of blood supply in
      fracture fragments, owing to less soft tissue and periosteal injury. When the
      procedure is performed with the lateral double incision, exposure and
      preservation of the axillary and radial nerves are necessary. Early return of
      function in the shoulder and elbow joints and favorable healing time are the
      major advantages of this method in this rare subset of humerus fractures.

PMID- 22659631
TI  - The results of minimally invasive percutaneous plate osteosynthesis (MIPPO) in
      distal and diaphyseal tibial fractures.
AB  - OBJECTIVE: The aim of this study was to evaluate the time to union and
      complications in cases of tibial diaphysis and distal tibial fractures fixed with
      a minimally invasive percutaneous plate. METHODS: Thirty-five patients (23 males,
      12 females) were operated on using minimally invasive percutaneous plate
      osteosynthesis (MIPPO) principles for tibial diaphysis and distal tibial
      fractures. Twenty-eight were closed and seven were open fractures. After direct
      or indirect fracture reduction, the plate was advanced through a submuscular
      extraperiosteal tunnel through the distal incision without opening the fracture
      line. The plate was fixed with screws through the proximal and distal incisions.
      Clinical and radiological evaluations were made at four to six week intervals
      after surgery. Full weight-bearing was allowed after an average of 14.43 (range:
      12 to 20) weeks and 15.39 (range: 8 to 32) weeks in open and closed fractures,
      respectively. Duration of the union and complications were analyzed. RESULTS: The
      mean duration of the union was 20.7 (range: 16 to 28) weeks and 17.96 (range: 10
      to 36) weeks in open and closed fractures, respectively. All cases showed union
      except one who had an implant failure. Necrosis at the wound developed in one
      case and infection in another. CONCLUSION: MIPPO is an effective alternative
      treatment for tibial diaphysis and distal tibia fractures with low complication
      and high union rates.

PMID- 22659632
TI  - Evaluation of the effects of disabilities due to traffic accidents on the quality
      of life using SF-36 health survey.
AB  - OBJECTIVE: The purpose of this study was to investigate the impact of
      disabilities caused by traffic accidents on quality of life using the SF-36
      health survey. METHODS: The study group included 168 patients (30 females and 138
      males) injured in traffic accidents referred to the Department of Forensic
      Medicine to obtain health reports indicating their degree of disability. One
      hundred twenty-two cases comprised the control group. The degree of disability
      for the injured body parts was determined based on the related section of the
      Disability Regulation for patients regarded as recovered based on examination and
      consultation. Quality of life was calculated using the SF-36 survey. Patients
      were additionally evaluated using the physical and mental component summary
      PCS/MCS) scores. RESULTS: A statistically significant difference was observed
      between the groups in terms of the injured body parts. The femur, tibia and/or
      fibula, vertebrae, radius and/or ulna and the humerus were the most frequently
      fractured bones. The degree of disability in the patient group was 19.22 +/-
      17.73. Together with the scores of the eight subscales of SF-36, the PCS and MCS
      score in the patient group were significantly lower when compared to the control
      group (p<0.05). CONCLUSION: An update is required in the Disability Regulation,
      including the addition of items on deterioration in the quality of life and pain,
      and the use of the SF-36 scale may be beneficial in this regard.

PMID- 22659633
TI  - Expectations in patients with total knee arthroplasty.
AB  - OBJECTIVE: The primary objective of total knee arthroplasty (TKA) is to decrease
      pain and restore functional knee joint. Current hypotheses indicate higher knee
      flexion is required in terms of life style, culture and expectations in Eastern
      communities. Therefore, society-specific features related to life style and
      cultural habits are needed. The objective of this study was to investigate the
      expectations of patients undergoing TKA. METHODS: The study included 131 patients
      (18 male, 113 female; mean age: 66.2 +/- 8.3 years) who underwent cemented TKA
      due to knee osteoarthritis. All patients were operated by the same surgeon using
      the same implant and surgical technique. Patients were evaluated using the
      Hospital for Special Surgery (HSS) knee score, a 15-item clinical knee assessment
      questionnaire and the HSS knee arthroplasty expectation questionnaire. RESULTS:
      Mean HSS score for the right knee was 89.2 +/- 10.5 and for the left knee was
      89.6 +/- 9.4. The two most expected outcomes were improvements in pain (99.2%)
      and gait (96.2%) and the two least expected outcomes were improvements in
      psychological well-being (22.9%) and communicative skills (35.1%). Expectations
      were not affected by education and working conditions. CONCLUSION: Patients' most
      expected outcomes were improvement in pain and restoration of function (gait,
      climbing stairs and no need of assistive devices), similar to Western and
      American communities.

PMID- 22659634
TI  - Tibial torsion: cause or consequence of osteoarthritis?
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship between
      torsional variations of the lower extremity and the development of medial
      osteoarthritis in the knee. METHODS: Computed tomography measurements of the
      femoral and tibial torsion were evaluated in 21 lower extremities of 19 patients
      with primary bilateral gonarthrosis and compared with 14 lower extremities of
      eight normal individuals. RESULTS: There was no statistically significant
      difference between lower extremities with and without gonarthrosis in terms of
      tibial torsion (26.20 degrees  +/- 9.78 degrees  and 25.32 degrees  +/- 11.50
      degrees ,respectively), femoral torsion (15.89 degrees  +/- 8.63 degrees  and
      13.91 degrees  +/- 7.26 degrees , respectively) and tibiofemoral index (10.30
      degrees  +/- 13.06 degrees  and 11.39 degrees  +/- 12.84 degrees ,respectively)
      (p>0.05). CONCLUSION: We conclude that medial compartment osteoarthritis in the
      early arthritic period is not always associated with torsional deformities of the
      lower limb.

PMID- 22659635
TI  - The outcomes of anterior cruciate ligament reconstructed and rehabilitated knees
      versus healthy knees: a functional comparison.
AB  - OBJECTIVE: In this study, we aimed to evaluate and compare the functional
      performance and muscle strength of cases of ACL reconstruction using bone
      patellar tendon-bone graft followed by rehabilitation with those of healthy
      subjects. METHODS: This study included fifteen patients (range: 20 to 35 years)
      who underwent ACL reconstruction 18 to 24 months previously and a control group
      of 15 healthy volunteers with similar characteristics. Cases were evaluated with
      physical examinations, functional tests, subjective scales (Lysholm, Hospital for
      Special Surgery Knee Score (HSSS), and Tegner activity scale) and isokinetic
      test. Differences between the reconstruction group and control group were
      analyzed. RESULTS: Significant differences were found in the activity level of
      the reconstruction group (p<0.05) and in the clinical findings of the subjects
      with involved and uninvolved legs (p<0.05). When the reconstructed and control
      groups were compared according to the limb symmetry index, there were significant
      differences in single-leg hop test, timed hop test, shuttle run and stair hop
      test (p<0.05). The study also revealed a significant correlation between the
      vertical hop and quadriceps strength in the isokinetic test (r=0.56). When the
      operated knees were compared to the healthy side, mean limb symmetry index was
      over 92% (with two cases at 88%). When the dominant leg was compared to the non
      dominant leg in the control group, the mean limb symmetry index was over 95%.
      CONCLUSION: Functional outcomes similar to those of healthy legs can be achieved
      following ACL reconstruction with bone-patellar tendon-bone grafting and
      rehabilitation. The similar functional test results of the operated and healthy
      subjects prove the effectiveness of the rehabilitation program.

PMID- 22659636
TI  - Intraobserver reliability of modified Ashworth scale and modified Tardieu scale
      in the assessment of spasticity in children with cerebral palsy.
AB  - OBJECTIVE: The aim of this study was to analyze the intraobserver reliability of
      the Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS) in the
      assessment of spasticity in children with cerebral palsy (CP). METHODS: Elbow
      flexor muscles, wrist flexor muscles, hip adductors, hamstrings, gastrocnemius
      and soleus muscles of 37 children (mean age: 8.97+/-4.41) with spastic CP were
      evaluated using the MAS and MTS according to the severity of spasticity. RESULTS:
      Intraobserver reliability of MAS was significant for all assessments (p<0.01) and
      reliability ranged from 'low' to 'average'. The reliability of MTS was
      significant for all assessments (p<0.01) and intraobserver reliability ranged
      among 'average', 'good' and 'excellent'. CONCLUSION: Although the high
      intraobserver reliability for MTS to assess spasticity level in muscles of
      children with CP will improve usage of this scale, new research testing the
      intraobserver reliability of this scale is needed.

PMID- 22659637
TI  - Cytotoxicity of local anesthetics to rats' articular cartilage: an experimental
      study.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of both in vivo and
      in vitro bupivacaine, levobupivacaine and tramadol on articular cartilage and
      chondrocytes in experimental rat models. METHODS: Thirty mature Sprague Dawley
      rats weighing 230-300 g were randomized into 3 groups. Bupivacaine (Group 1),
      levobupivacaine (Group 2) and tramadol (Group 3) were injected into the right
      knee joints and a physiological 0.9% saline into the left. From each group, 5
      rats were executed 48 hours following drug administration after 5 and 10 days.
      The specimens were fixed, decalcified and stained with hematoxylin & eosin and
      toluidine blue. All samples were histopathologically evaluated according to the
      recommendation of ICRS' osteoarthritis and cartilage histopathology grading and
      staging system. Articular cartilage cells of the rats were cultured and seeded
      into cell culture flasks. Cartilage cell seeded samples (104 cells/ml) were
      incubated in three different anesthetic agents (0.5%); bupivacaine,
      levobupivacaine, and tramadol, respectively. CellTiter 96((r)) Non-Radioactive
      Cell Proliferation (MTS) assay was used to determine the cell density on the
      samples. RESULTS: Statistically significant higher OARSI grades and OA stage and
      scores were detected when comparing the group injected with levobupivacaine and
      executed after 10 days with the levobupivacaine injected group killed after 48
      hours (p<0.01 [p=0.008]). Although, statistical analysis could not be done due to
      insufficient number of samples in the in vitro part of the experiment, it can be
      concluded that tramadol is cytotoxic to rat chondrocyte in vitro after 30 min of
      exposure. Additionally, cell numbers in both the bupivacaine and levobupivacaine
      treated wells showed decrease throughout 15, 30 and 60 minute exposures.
      CONCLUSION: Although chondrotoxicity of bupivacaine was less harmful than
      levobupivacaine and tramadol, these findings suggest that local anesthetics may
      negatively affect articular cartilage and chondrocytes.

PMID- 22659638
TI  - Use of a perichondrial autograft on the peritendinous adhesion: an experimental
      study in rabbits.
AB  - OBJECTIVE: The aim of this experimental study was to evaluate the use of a
      clinically available perichondrium graft as an adjunct to surgical tendon repair.
      METHODS: Eight male New Zealand white rabbits of similar height and weight were
      used in this study. The left and right Achilles tendons were used as the
      experimental and control group, respectively. Perichondrium grafts were harvested
      from the right ears of the rabbits. Both Achilles tendons were clearly cut and
      repaired. After the repair, the perichondrium graft was wrapped around the tendon
      repair sites of the left Achilles tendons. Rabbits were sacrificed after six
      weeks and the tendons were examined macroscopically and histopathologically.
      RESULTS: Macroscopically and histopathologically, less adhesion occurred when the
      perichondrium graft was wrapped around the tendon repair site compared to the
      control group. CONCLUSION: Perichondrium graft may isolate the repaired tendon
      and may reduce scar formation and adhesions during the healing period.

PMID- 22659639
TI  - Ogilvie's syndrome following bilateral knee arthroplasty: a case report.
AB  - Ogilvie's syndrome, also known as acute colonic pseudo-obstruction, is an
      uncommon but severe postoperative complication of total hip and knee
      arthroplasty. This syndrome should be borne in mind after arthroplasty surgery.
      We present a case of this serious postoperative complication and aim to identify
      the risk factors and alert surgeons to the possibility and appropriate management
      of Ogilvie's syndrome.

PMID- 22659640
TI  - Tuberculosis of the pubic symphysis masquerading as osteitis pubis: a case
      report.
AB  - Tuberculosis is one of the oldest diseases affecting mankind and is known for its
      ability to present in various forms and guises. Pubic symphysis is an uncommon
      site for tuberculous affliction; hence very few cases have been reported in the
      English-language literature. We present a rare case of pubic symphysis
      tuberculosis diagnosed as osteitis pubis before presentation to our institution.
      The patient made an uneventful recovery following antitubercular chemotherapy.

PMID- 22659641
TI  - Monitoring enzymatic degradation of pericellular matrices through SERS stamping.
AB  - We introduce a surface enhanced Raman spectroscopy (SERS) stamping approach for
      acquiring cell-surface specific vibrational spectra of individual living cells
      under physiological conditions. The SERS stamping approach utilizes a
      nanostructured metal surface on top of a lithographically defined piston that can
      be translated in 3-dimensions with nanometer resolution to contact living cells
      in solution with a pristine metal surface. We applied this approach to
      characterize the chemical composition of the cellular surface of living MCF7
      breast cancer cells and to monitor its change upon addition of the enzyme
      hyaluronidase, which degrades major constituents of the pericellular matrix.
      Although the cell surface spectra show significant cell-to-cell fluctuations, a
      statistical barcode analysis of the spectra ensembles reveals systematic changes
      in the cell surface SERS spectra upon addition of hyaluronidase, which are
      consistent with a thinning of the pericellular matrix.

PMID- 22659642
TI  - The role of interoception in addiction: a critical review.
AB  - Interoception refers to a collection of processes by which the state of the body
      is transmitted back to the brain, giving rise to awareness of the internal
      milieu, and motivating behavioural responses to homeostatically regulate internal
      state. Recent work has begun to explore the relevance of this construct to drug
      addiction: drugs of abuse and drug-related stimuli induce pronounced peripheral
      changes, and damage to a brain region known to support interoception (the insula)
      disrupts nicotine dependence. This article critically reviews existing accounts
      of addiction that suggest impaired interoception contributes to drug abuse.
      Conceptually, we argue that existing addiction interoception models could be
      usefully extended by considering (i) the multiple components of the bodily
      feedback system (signal, perception, and appraisal) and (ii) how individual
      differences in these three components impact on cognitive-affective processing in
      addiction. Empirically, whilst no studies have examined direct behavioural
      measures of interoception in addicted populations, several indirect lines of
      experimental work that pertain to this altered interoception hypothesis are
      presented. Clinical implications are discussed.

PMID- 22659643
TI  - Intra-amygdala infusion of the protein kinase Mzeta inhibitor ZIP disrupts
      foreground context fear memory.
AB  - Protein kinase Mzeta has been the subject of much recent interest, as it is the
      only molecule currently identified to maintain memory. Despite the wealth of
      studies investigating PKMzeta in memory, questions remain about which types of
      memory PKMzeta supports. Further, it is unclear how long the inhibitor of PKMz,
      zeta-pseudosubstrate inhibitory peptide (ZIP) remains in the brain after
      infusion. Here, we demonstrate that foreground context fear memory requires
      PKMzeta activity in the amygdala. We also show that ZIP is fully cleared from the
      brain by 24h after infusion. These data contribute to a growing body of
      literature that demonstrates that PKMzeta plays a key role in maintaining
      amygdala-dependent memory and provides new information about the degradation
      timecourse of the most commonly used inhibitor of PKMzeta, ZIP.

PMID- 22659644
TI  - Expanding the table: the web as a tool for participatory adaptive management in
      California forests.
AB  - Participatory adaptive management is widely promoted as the new paradigm in
      public lands management. It is grounded in two underlying principles - that
      management experiments and diverse sources of information should be used to
      continually refine management in complex ecological systems, and that the public
      must be included throughout the adaptive management process. Access to scientific
      results and exchange of information is at the core of both of these principles.
      The recent proliferation of Internet communities and web-based participation
      tools raises the question of how the Internet might help facilitate information
      exchange in participatory adaptive management. Using a case study approach, the
      role of web technologies in facilitating the flow of transparent and useful
      information was examined in a participatory adaptive management project focused
      on Forest Service vegetation management treatments in California's Sierra Nevada.
      Three evaluation methods were used: analysis of web usage and content, a survey
      of active participants, and a review of comments posted to the project website.
      Results suggest that the web played an important role throughout the adaptive
      management cycle by supporting communication through disseminating information to
      the public and increasing the transparency of the scientific process. The web
      played a small, but important role in public consultation, by providing a forum
      for targeted questions and feedback from the public. Internet technology did not
      actively support the two-way flow of information necessary for mutual learning.
      Web technology complements face-to-face interactions and public meetings, rather
      than replacing them.

PMID- 22659645
TI  - Assessment of the use potential of edible sea urchins (Paracentrotus lividus)
      processing waste within the agricultural system: influence on soil chemical and
      biological properties and bean (Phaseolus vulgaris) and wheat (Triticum vulgare)
      growth in an amended acidic soil.
AB  - In this study we evaluated the influence of ground purple sea urchin
      (Paracentrotus lividus) endoskeletons, a processing waste common to all edible
      sea urchin plants, on the chemical, biochemical and microbiological features of
      an acidic (pH 5.65) sandy-loam soil. The purple sea urchin endoskeletons were
      characterized by a high content of total carbonates (~94%), a moderately alkaline
      pH in water (pH 7.88) and electrical conductivity values (3.55 mS/cm) very
      similar to those of commercial lime. To evaluate the influence of the P. lividus
      endoskeletons on soil properties four different amendment rates were tested,
      notably 0.5, 1.0, 3.0 and 5.0% based on soil dry weight, and the effects compared
      with those recorded on unamended control soil. The addition of the purple sea
      urchin processing waste caused an immediate and significant pH increase which was
      positively related to the rate of the amendment addition. After a six months
      equilibration period, the differences in soil pH were still evident and
      significant increases of electrical conductivity and available phosphorus were
      also detected in soils with the higher amendment rates. The number of
      heterotrophic and cellulolytic bacteria and actinomycetes significantly increased
      after amendment addition while the number of culturable fungi steadily declined.
      The analysis of the Biolog Community Level Physiological Profile indicated a
      clear influence of the purple sea urchin processing waste on the structure of the
      native microbial community while a significant increase of microbial
      functionality (i.e. dehydrogenase activity) was recorded in soil treated with the
      higher amendment rates (i.e. 3.0 and 5.0%). The improvement of microbial
      abundance and functionality as well as the change of the microbial community
      structure were ascribed to the pH shift induced by the P. lividus processing
      waste. To investigate possible effects on soil fertility, dwarf bean (Phaseolus
      vulgaris) and wheat (Triticum vulgare) growth were also assessed in a pot
      experiment. Plant growth was unaffected (wheat) or stimulated (bean) by the
      amendment addition in the 0.5-3.0% range while the higher amendment rate (i.e.
      5.0%) was detrimental for both plant species indicating a phytotoxic effect which
      could be due to different factors such as an excess of calcium in soil, a
      suppression of Mg uptake or the higher EC values detected at the highest
      amendment rate. It is concluded that ground P. lividus endoskeletons have
      potential as a soil amendment to ameliorate chemical and biological properties of
      acidic Mediterranean soils. This seems particularly relevant, especially at the
      lower amendment rates, since for the first time, a sustainable management system
      is proposed for P. lividus processing waste, which foresees economic value in the
      sea urchin by-product through its re-use within the agricultural production
      system.

PMID- 22659646
TI  - What impact might mitigation of diffuse nitrate pollution have on river water
      quality in a rural catchment?
AB  - Observations of river flow, river quality and solar radiation were collated to
      assess the degree to which light and nutrients may be limiting phytoplankton
      growth at seven sites in the River Ouse catchment in NE England under average
      conditions. Hydraulic information derived from river network model applications
      was then used to determine where river water has sufficient residence time above
      the tidal limit to facilitate bloom development. A nitrate model (NALTRACES) was
      developed to estimate the impact of land management change on mean river nitrate
      concentrations. Applications of this model showed that although agricultural
      activity contributes substantially to nitrate loads in the Ouse it is likely to
      have little impact on phytoplankton growth, which could still occur extensively
      in its absence given favourable sunny and dry conditions. As an example of a
      means of controlling light availability, establishing full riparian tree cover
      would appear to be a considerably more effective management scenario than
      suppressing inputs to the river of nitrate or phosphorus. Any actions should be
      prioritised in headwater areas such as the upper reaches of the Swale and Ure
      tributaries. These conclusions are in broad agreement with those arising from
      more detailed simulations at daily resolution using the QUESTOR river quality
      model. The combination of simple modelling approaches applied here allows an
      initial identification of suitable spatially-targeted options for mitigating
      against phytoplankton blooms which can be applied more widely at a regional or
      national level.

PMID- 22659647
TI  - When it comes to electric vehicle emissions, location matters.

PMID- 22659648
TI  - Six-month hemoglobin concentration and its association with subsequent mortality
      among adults on antiretroviral therapy in Lusaka, Zambia.
AB  - Little is known about changes in hemoglobin concentration early in the course of
      antiretroviral therapy and its subsequent relation to survival. We analyzed data
      for 40,410 HIV-infected adults on antiretroviral therapy in Lusaka, Zambia. Our
      main exposure of interest was 6-month hemoglobin, but we stratified our analysis
      by baseline hemoglobin to allow for potential effect modification. Patients with
      a 6-month hemoglobin <8.5 g/dL, regardless of baseline, had the highest hazard
      for death after 6 months (hazard ratio: 4.5; 95% confidence interval: 3.3 to
      6.3). Future work should look to identify causes of anemia in settings such as
      ours and evaluate strategies for more timely diagnosis and treatment.

PMID- 22659649
TI  - HIV-1 is not a major driver of increased plasma IL-6 levels in chronic HIV-1
      disease.
AB  - OBJECTIVE: Increased plasma IL-6 levels have been associated with HIV-1 disease
      progression risk, yet the drivers of IL-6 production in HIV-1 infection are not
      known. This study was designed to explore the relationship between HIV-1
      replication and IL-6 induction. DESIGN: Correlations between plasma levels of IL
      6 and HIV-1 RNA were examined in 2 clinical studies. To more directly assess the
      induction of IL-6 by HIV-1, several cell and tissue types that support HIV-1
      replication in vivo were infected with HIV-1, and expression of IL-6 was
      measured. METHODS: Spearman rank correlations were used to examine the
      relationship between plasma levels of IL-6 and HIV-1 RNA. Macrophages and colonic
      and lymph node histocultures were infected with HIV-1 or stimulated with
      bacterial products, lipopolysaccharide (LPS) or flagellin, and IL-6 levels in
      supernatant were measured by enzyme-linked immunosorbent assay or multiplex bead
      assay. RESULTS: In the clinical studies, there was weak or no correlation between
      plasma levels of IL-6 and HIV-1 RNA, but IL-6 levels were correlated with plasma
      levels of the LPS coreceptor CD14. Macrophages stimulated with LPS or flagellin
      showed robust production of IL-6, but there was no increase in IL-6 production
      after HIV-1 infection. IL-6 expression was not increased in lymph node
      histocultures obtained from HIV-1-infected subjects nor after productive HIV-1
      infection of colonic or lymph node histocultures ex vivo. CONCLUSIONS: We find no
      evidence that HIV-1 replication is an important driver of IL-6 expression in vivo
      or in in vitro systems.

PMID- 22659650
TI  - Rapid point-of-care CD4 testing at mobile HIV testing sites to increase linkage
      to care: an evaluation of a pilot program in South Africa.
AB  - BACKGROUND: A mobile HIV counseling and testing (HCT) program around Johannesburg
      piloted the integration of point-of-care (POC) CD4 testing, using the Pima
      analyzer, to improve linkages to HIV care. We report results from this pilot
      program for patients testing positive (n = 508) from May to October 2010.
      METHODS: We analyzed 3 primary outcomes: assignment to testing group (offered POC
      CD4 or not), successful follow-up (by telephone), and completed the referral
      visit for HIV care within 8 weeks after HIV testing if successfully followed up.
      Proportions for each outcome were calculated, and relative risks were estimated
      using a modified Poisson approach. RESULTS: Three hundred eleven patients were
      offered the POC CD4 test, and 197 patients were not offered the test. No
      differences in patient characteristics were observed between the 2 groups.
      Approximately 62.7% of patients were successfully followed up 8 weeks after HIV
      testing, with no differences observed between testing groups. Among those
      followed up, 54.4% reported completing their referral visit. Patients offered the
      POC CD4 test were more likely to complete the referral visit for further HIV care
      (relative risk 1.25, 95% confidence interval: 1.00 to 1.57). CONCLUSIONS: In this
      mobile HCT setting, patients offered POC CD4 testing as part of the HCT services
      were more likely to visit a referral clinic after testing, suggesting that rapid
      CD4 testing technology may improve linkage to HIV care. Future research can
      evaluate options for adjusting HCT services if POC CD4 testing was included
      permanently and the cost-effectiveness of the POC CD4 testing compared with other
      approaches for improving linkage of care.

PMID- 22659651
TI  - Corticotropin-releasing hormone regulates common target genes with divergent
      functions in corticotrope and neuronal cells.
AB  - As a key regulator of the neuroendocrine stress axis and as a neuromodulator in
      the brain, the neuropeptide corticotropin-releasing hormone (CRH) plays an
      important role in various diseases of the central nervous system. Its cognate
      receptor CRH receptor type 1 (CRHR1) is a potential novel target for the
      therapeutic intervention in major depressive disorder. Therefore, a more precise
      understanding of involved intracellular signaling mechanisms is essential. The
      objective of this project was to identify specific target genes of CRHR1-mediated
      signaling pathways in the corticotrope cell line AtT-20 and in the neuronal cell
      line HN9 using microarray technology and qRT-PCR, respectively. In addition, we
      assessed the capacity of validated target genes to directly impact on CRHR1
      dependent signaling using reporter assays. Thereby, we identified a set of CRHR1
      downstream targets with diverging and cell type-specific roles which strengthen
      the role of CRH and CRHR1 as dynamic modulators of a variety of signal
      transduction mechanisms and cellular processes.

PMID- 22659652
TI  - [Molecular epidemiological characteristics of clinically isolated carbapenem
      resistant Acinetobacter baumannii in Changsha].
AB  - OBJECTIVE: To survey antibiotic resistance of clinical isolates of Acinetobacter
      baumannii in Changsha and to investigate molecular epidemiological
      characteristics of carbapenem-resistant Acinetobacter baumannii. METHODS: A total
      of 205 non-duplicated, clinical isolates of Acinetabacter baumannii from 10
      general hospitals in Changsha were collected from March 2010 to December 2010.
      The K-B disk diffusion method was applied for the drug-susceptibility test; a
      modified, double-disk synergy test was used to detect metallo-beta-lactamase
      (MBL), and a modified Hodge test was used for the screening of carbapenemase. PCR
      was used to amplify carbapenemase genes (including OXA-23, OXA-24, OXA-51, IMP-1,
      and VIM-2) and the positive products were sequenced. Enterobacterial repetitive
      intergenic consensus PCR (ERIC-PCR) was used for DNA typing and test of homology.
      RESULTS: Of the 18 antibiotics tested, 14 had a high rate of resistance (>50% of
      the isolates tested), with piperacillin the highest (80.5% of strains), and
      cefoperazone/sulbactam the lowest (2.5%). In total, 115 carbapenem-resistant
      Acinetobacter baumannii strains were confirmed, but their MBL phenotype and genes
      were all negative. Seventy-one positive strains were detected by the modified
      Hodge test, among which 64 strains were OXA-23-positive. All the 115 strains were
      positive for the amplification of the OXA-51 gene, and no strain was found which
      carried OXA-24 or OXA-58 gene. Seven genomic types were included in the 115
      Acinetobacter baumannii. The major prevalence types were Type B ( 72 strains) and
      Type A (19 strains). CONCLUSION: Multiple drug resistance of clinically isolated
      Acinetobacter baumannii is a serious problem in Changsha. Production of OXA-23
      and OXA-51 carbapenemases is an important mechanism of resistance to carbapenem
      antibiotics, and there is prevalence of the same clones in these carbapenem
      resistant strains.

PMID- 22659653
TI  - [Measurement of Rho-kinase in peripheral blood monocytes in patients with
      pulmonary arterial hypertension related to chronic obstructive pulmonary
      diseases].
AB  - OBJECTIVE: To determine effects of the RhoA/Rho kinase signaling pathway on
      patients with pulmonary arterial hypertension related to chronic obstructive
      pulmonary diseases by testing levels of Rho-associated coiled-coil containing
      protein kinase 1(ROCK1) in peripheral blood monocytes in healthy subjects,
      patients with chronic obstructive pulmonary diseases (COPD), and patients with
      pulmonary arterial hypertension related to COPD. METHODS: Ten healthy subjects
      (Group A), 10 patients with COPD (Group B), and 10 patients with pulmonary
      arterial hypertension related to COPD (Group C) were enrolled, all of whom were
      hospitalized in the Third Hospital of Changsha between Dec. 2010 and Apr. 2011.
      Twenty milliliters of blood was collected from each subject. The peripheral blood
      mononuclear cells (PBMC) were separated by Percoll and, monocytes were incubated.
      Levels of ROCK1 in the three groups were measured by ELISA. The pulmonary
      function was measured by spirometric tests, and the pulmonary arterial systolic
      pressure (PASP) was detected by color Doppler echocardiogram. RESULTS: 1)The PASP
      in Group C was significantly higher than that of Groups A and B(P<0.01). 2) The
      levels of ROCK1 in monocytes of Group C were higher than those of Groups A and
      B(P<0.05). The levels of ROCK1 in monocytes of Group B were higher than those of
      Group A (P<0.05). 3) The levels of ROCK1 in monocytes of the three groups showed
      a positive correlation with PASP(r=0.661, P<0.05). 4) The levels of ROCK1 in
      monocytes of the three groups showed a negative correlation with forced
      expiratory volume at the first second/ forced vital capacity (FEV1%)(r=0.131,
      P>0.05). CONCLUSION: Rho kinase plays a key role in the pathogenesis of pulmonary
      arterial hypertension. The ROCK1 may be a marker of the severity of pulmonary
      arterial hypertension related to COPD.

PMID- 22659654
TI  - [Comparison of growth of human fetal RPE cells on electrospun nanofibers and
      etched pore polyester membranes].
AB  - OBJECTIVE: To investigate and compare the growth of human fetal retinal pigment
      epithelial (RPE) cells seeded onto electrospun polyamide nanofibers (EPN) or
      etched pore polyester (EPP), and, further, to explore their possible use as
      prosthetic Bruch's membrane. METHODS: Human fetal RPE cells were planted onto the
      EPN, EPP and plastic (control) substrates in Transwells. The cultures were
      assessed with respect to cell attachment at 2, 4, 8 hours and proliferation at 1,
      4, 8 days after seeding. Growth and morphology of the cells were monitored under
      the phase contrast microscope, and the phenotype was identified by
      immunofluorescence staining with antibodies against tight junction protein ZO-1.
      Strips of single EPP coated with nothing or EPP coated with EPN was differently
      implanted into the subretinal space of two P21 RCS rats for two weeks and the
      histologic slides of the retina were assessed. RESULTS: Cultured human fetal RPE
      cells were attached to either EPN or EPP substrates (with seeding on plastic
      substrate as control). After 8 h, the numbers of adherent cells in the EPN, EPP
      and control groups were 1.23*10(5)/cm(2), 1.70*10(5)/cm(2), and 1.64*10(5)/cm(2),
      respectively. The number of RPE cells attached to EPN was obviously less than
      that to both EPP and control (P<0.05). On the first day, the proliferation of
      cells on EPN was less than that of EPP and control (P<0.05); but by the 8th day
      in culture, the proliferation of cells on EPN had increased and was higher than
      proliferation on both EPP and control (P<0.05). All of the RPE cells cultured on
      EPN and EPP substrates were in monolayer, and the EPN-attached cells resembled
      the inner collagenous layer of Bruch's membrane. Immunofluorescence staining
      showed that the RPE cells cultured on EPN and EPP substrates adopted a higher
      expression of ZO-1 than that on the plastic control substrate. Subretinal
      implantation of either EPP alone or EPP as a carrier for free EPN for 2 weeks in
      P21RCS rats resulted in an expected encapsulation and loss of photoreceptor
      layer. No toxicity or other adverse reaction was observed in the vicinity of the
      transplant. CONCLUSION: EPN and EPP could maintain human fetal RPE cell
      attachment and proliferation. Both EPN and EPP appeared to be grossly tolerance
      and biocompatible with subretinal implantation. EPN represents an intriguing
      prospect for prosthetic Bruch's membrane replacement because of its similarity in
      structure to native Bruch's membrane.

PMID- 22659655
TI  - [Role of phosphorylation of MARCKS-PSD in the secretion of MUC5AC induced by cold
      temperatures in human airway epithelial cells].
AB  - OBJECTIVE: To construct phosphorylation sites domain (PSD) mutant of
      myristoylated alaninerich C kinase substrate (MARCKS) and explore the role of
      transient receptor potential melastatin 8 cation channels (TRPM8) and MARCKS in
      cold-induced synthesis and exocytosis of mucin (MUC) 5AC. METHODS: Human
      placental cDNA was used as a template to amplify the full coding region of MARCKS
      cDNA by PCR. Ser159, Ser 163, Ser 167, Ser 170 in the PSD were mutated to
      aspartic acids by an overlap PCR method. The resultant PSD mutant cDNA and the
      wild-type MARCKS cDNA were each subcloned into a mammalian expression vector
      pcDNA3.0. Recombinant constructs were confirmed by restriction enzyme digestion
      analysis and DNA sequencing. In intervention experiments, cells were pretreated
      with the TRPM8 channel antagonist BCTC and transfected with MARCKS-PSD mutant
      cDNA, and thereafter cold stimulation was applied. The levels of MUC5AC were
      measured by immunofluorescence and ELISA to clarify the roles of TRPM8 and PSD
      mutant on the synthesis and secretion of MUC5AC induced by cold, respectively.
      RESULTS: Restriction enzyme digestion analysis and DNA sequencing revealed that
      the pcDNA3.0- MARCKS and pcDNA3.0-MARCKS-PSD mutants were successfully
      constructed. The levels of intracellular and secreted MUC5AC of cold treated
      group were significantly higher than those of control group (P<0.05). BCTC
      attenuated the cold-induced synthesis and secretion of MUC5AC when compared with
      cold treated group (P<0.05). Transfection of 16HBE cells with the MARCKS-PSD
      mutant cDNA resulted in significant inhibition of mucin secretion in response to
      cold, and significantly higher level of intracellular MUC5AC than that of control
      group (P<0.01), whereas transfection with the vector DNA or the wild-type MARCKS
      cDNA had no effect on the mucin synthesis and secretion in response to cold
      (P>0.05). CONCLUSION: TRPM8 and phosphorylation of MARCKS-PSD mediates the cold
      induced exocytosis of MUC5AC by airway epithelial cells.

PMID- 22659656
TI  - [Effect of probucol on serum malondialdehyde and superoxide dismutase in patients
      with primary hypertension].
AB  - OBJECTIVE: To observe the therapeutic effect of probucol on serum malondialdehyde
      (MDA) and superoxide dismutase (SOD) in patients with primary hypertension.
      METHODS: A randomized study was performed on 40 patients with hypertension. The
      patients were randomly assigned to the control (levamlodipine besylate 2.5 mg/d
      plus benazepril 10 mg/d, n=20) or probucol group (levamlodipine besylate 2.5 mg/d
      plus benazepril 10 mg/d plus probucol 500 mg/d, n=20). An additional twenty
      healthy people were enrolled in the study (normal group). All subjects were
      followed up for a period of four weeks. Lipids and hepatic/renal function were
      measured at baseline and after 4 weeks. The levels of serum MDA and SOD activity
      were assayed by chemical colorimetry, and other indices, including blood
      pressure, lipids and hepatic/renal function, were measured at baseline and after
      4 weeks. RESULTS: Compared to the normal group, the levels of MDA in all of the
      hypertension patient groups were higher, SOD was lower. The antihypertensive
      treatment decreased serum MDA levels but increased SOD content, and probucol
      treatment exaggerated these effects, with greater reduction of serum MDA levels
      and greater increase of SOD content. CONCLUSION: The treatment with probucol can
      improve oxidative stress in hypertension patients, resulting in reduced serum MDA
      levels and improved SOD activity, thus contributing agreater antihypertensive
      effect.

PMID- 22659657
TI  - [Effect of total glucosides of peony on expression and DNA methylation status of
      ITGAL gene in CD4(+) T cells of systemic lupus erythematosus].
AB  - OBJECTIVE: To investigate the effect of total glucosides of peony (TGP) on
      expression and DNA methylation status of ITGAL gene (CD11a) in CD4(+) T cells
      from patients with systemic lupus erythematosus (SLE). METHODS: CD4(+) T cells
      were isolated by positive selection using CD4 beads. CD4(+) T cells were treated
      by TGP at 0, 62.5, 312.5 and 1562.5 mg/L for 48 h. The MTT method was used to
      assess cell viability; mRNA expression level was measured by realtime-PCR;
      protein level of CD11a was measured by flow cytometric analysis; DNA methylation
      status was assayed by bisulfite sequencing. RESULTS: No significant change in
      cell viability was found in CD4(+) T cells among the different concentration
      groups (P>0.05). Compared with control, the mRNA and protein levels of ITGAL were
      down-regulated significantly in SLE CD4(+) T cells treated with TGP (1562.5 mg/L)
      (P< 0.01). Furthermore, the extent of DNA methylation of ITGAL promoter was
      increased in TGP (1562.5 mg/L) treated CD4(+) T cells compared with control group
      (P<0.01). CONCLUSION: TGP can repress CD11a gene expression through enhancing DNA
      methylation of ITGAL promoter in CD4(+) T cells from patients with SLE. This
      observation represents a preliminary step in understanding the mechanism of TGP
      in SLE therapy.

PMID- 22659658
TI  - [Influence of different extracts from persimmon leaves on the antioxidant
      activity in diabetic mice].
AB  - OBJECTIVE: To investigate the antioxidant effect of different solvent extracts
      from persimmon leaves (PL) in diabetic mice induced by streptozotocin (STZ).
      METHODS: The total ethanol-extracted fraction of PL was further extracted with
      chloroform, ethyl acetate and n-butanol, in that order, the residues after
      ethanol extraction were water-extracted and alcohol-precipitated, and
      concentrated. The hypoglycemic effects of different solvents extracts from PL
      were evaluated in diabetic mice induced by STZ. The experimental mice were
      randomly divided into groups: control group, model group, glibenclamide group,
      low and high dosage groups of the various solvent extracts. The drugs were
      administrated to mice in every morning for 15 days. During this time period, the
      contents of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined.
      RESULTS: The water-extracted and ethanol-precipitated fractions and the ethyl
      acetate-extracted fraction markedly reduced the content of MDA and increased the
      activity of SOD in the livers of STZ-induced diabetic mice (P<0.01 or P<0.05).
      The chloroform-extracted and n-butanol-extracted fraction did not markedly reduce
      the content of MDA nor increase the activity of SOD in liver of STZ-induced
      diabetic mice (P>0.05). CONCLUSION: The ethyl acetate-extracted fraction, water
      extracted and ethanol-precipitated fraction of persimmon leaves have potential
      value in the treatment of diabetes. The mechanism of action of the antioxidant is
      related to the hypoglycemic effects of extracts from persimmon leaves.

PMID- 22659659
TI  - [Dosimetric comparison of intensity-modulated arc radiotherapy and fixed beam
      dynamic intensity-modulated radiation therapy in nasopharyngeal carcinoma].
AB  - OBJECTIVE: To compare the dosimetric differences of dosiology between intensity
      modulated arc radiotherapy (IMAT) and dynamic intensity-modulated radiation
      therapy (dIMRT) in nasopharyngeal carcinoma. METHODS: CT data from 25 patients
      treated in our radiotherapy center were selected randomly for this study. For
      each patient, the IMAT technique and the fixed beam dIMRT technique were
      accomplished by the simultaneously integrated boost. Dose volume histogram (DVH)
      data, isodose distribution, monitor units (MUs) and treatment time were compared
      in the two techniques. RESULTS: There was no significant difference between the
      IMAT and the dIMRT in dose received by 95% of target volumes (D(95)) (P>0.05).
      Overall, the mean dose (D(mean)), maximal dose (D(max)) and volume percentage
      receiving at least of 107% of the prescribed dose (V(107%)) of planning target
      volume (PTV) for the IMAT were increased slightly ,compared with the dlMRT
      (P<0.05). There were no significant differences in dosimetric indices of organs
      at risk (OARs) including spinal cord,optical nerves,lens and temporomandibular
      joints in the two techniques (P>0.05). Compared with the dlMRI, the D(max) of
      brain stem for the IMAT was increased slightly (P<0.05). Similar trends was
      observed for the D(mean) and dose received by 50% of volume (D(50)) of the left
      and right parotid glands (P<0.05). Healthy tissue (defined as the volume of the
      body minus PTV,B-P) irradiated from 800 cGy in the IMAT was higher, and that from
      1200-4500 cGy was lower compared with the dlMRI (P<0.05).The average number of
      MUs was reduced by 62.7% per fraction, and the treatment time was on average
      reduced by 60.1% per fraction in the IMAT compared with the dlMRI. CONCLUSION:
      There is a slight difference in dosiology between the two radiotherapy techniques
      investigated, but they both meet the clinical requirement. Compared with the
      dIMRT, the IMAT delivers less irradiation to healthy tissue, uses fewer MUs and
      takes less time during radiotherapy for nasopharyngeal carcinoma.

PMID- 22659660
TI  - [Differential expression of DJ-1 and HSP27 in invasive and non-invasive pituitary
      adenomas].
AB  - OBJECTIVE: To explore whether oncogenes DJ-1 and HSP27 are associated with
      invasiveness of human pituitary adenoma. METHODS: Total proteins were extracted
      from samples of 20 invasive and 20 non-invasive pituitary adenomas and the
      expression of DJ-1 and HSP27 was analyzed by Western blot. The correlation of DJ
      1and HSP27 with the invasiveness of pituitary adenoma was analyzed. RESULTS: The
      strong positive rates of DJ-1 and HSP27 in the 20 invasive pituitary adenoma were
      70% (14/20) and 80% (16/20), respectively. The invasive group had significantly
      higher expression of DJ-1 and HSP27 proteins than the noninvasive group [10%
      (2/20), 10% (2/20), respectively]. There was a positive correlation between the
      expression of DJ-1, HSP27 proteins and the invasiveness of pituitary adenoma as
      judged by the Spearman rank correlation test (P<0.05). CONCLUSION: The
      proliferative activity and abnormal expression of oncogenes DJ-1 and HSP27 may
      play a significant role in tumorigenesis and progression of pituitary adenoma.
      There was a significant correlation between the expression of DJ-1 and HSP27 and
      the invasiveness of pituitary adenoma.

PMID- 22659661
TI  - Application of retroperitoneal laparoscopic partial nephrectomy for renal cell
      carcinoma of the early stage.
AB  - OBJECTIVE: To evaluate the feasibility and clinical efficacy of retroperitoneal
      laparoscopic nephronsparing surgery for renal cell carcinoma of the early stage.
      METHODS: Between June 2003 and June 2008, 53 patients (31 males and 22 females)
      with renal mass were selected to undergo wedge resection of the tumor through
      retroperitoneal laparoscopy. Spiral computerized tomography (CT) and color
      Doppler ultrasound were used to provide information for nephron-sparing surgery
      (NSS). Patients with small (<= 3 cm), peripheral, shallow and exophytic tumors,
      at a distance which exceeded approximately 10 mm between the tumor and renal
      collecting system, were enrolled into our studies. Surgical resection was
      performed along a resection line about 0.5 cm from the tumors. RESULTS: All
      procedures were technically successful. Mean operating time was 96 min (ranging
      from 75 to 110 min). Mean warm ischemia time was 15 min (ranging from 10 to 21
      min). Mean estimated blood loss was 70 mL (ranging from 40 to 120 mL). Mean
      hospital stay after the surgery was 4.2 days (ranging from 3 to 6 days). No
      intraoperative or postoperative complications occurred. Of 53 patients, 52 had
      negative surgical margins and a 63-year male patient had a positive surgical
      margin. Neither local recurrence nor trocar-site metastasis was observed in the
      53 patients during follow ups averaging 39 months (ranging from 11 to 83 months).
      CONCLUSION: Under the modified techniques of the surgery and conservative
      criteria for patient selection, laparoscopic partial nephrectomy can be safely
      and effectively performed and satisfactory outcomes are achievable.

PMID- 22659662
TI  - Limping gait improvement by femoral lengthening in ankylotic hips and limb length
      discrepancy in young adults.
AB  - OBJECTIVE: To investigate the clinical improvement of limping gait in patients
      with ankylotic hips and limb length discrepancy. METHODS: From 1996 to 2005, 12
      patients with ankylotic hips and limb length discrepancy were treated by
      distraction osteogenesis with a mono-lateral external fixator and an
      intramedullary nail. The limb length discrepancy was 6.20-12.50 (median 8.45) cm.
      Limping gait was classified according to the recommendations of the American
      Academy of Orthopedic Surgeons/Hip Society and scored according to Harris: no
      limping scored 11 points, mild limping scored 8 points, moderate limping scored 5
      points, while severe limping scored 0 points. Limping gait was severe in all
      patients pre-operatively and the total score was 0. RESULTS: All patients were
      followed up for 30.00-46.00 (median 38.55) months, and all reported improvement
      in limping gait. The gain in length was 6.00-12.50 (median 8.20) cm, and the mean
      residual limb length discrepancy was 0-0.50 (median 0.20) cm. The total treatment
      time was 41.00-82.00 (median 61.50) weeks , the lengthening time was 14.00-38.00
      (median 29.55) weeks. At the last follow-up, 10 patients had mild limping gait
      and 2 had moderate limping gait; the total score was 90.00. The median score was
      7.50 (P(25) was 8.00, P(75) was 8.00). According to Wilcoxon signed rank test,
      the post-operative limping gait scores were significantly higher than pre
      operative (P= 0.001). CONCLUSION: Femoral lengthening can improve the limping
      gait significantly in ankylotic hips and limb length discrepancy.

PMID- 22659663
TI  - [Diagnostic value of transcranial Doppler ultrasound in early stage cerebral
      arteriosclerosis].
AB  - OBJECTIVE: To investigate the diagnostic value of transcranial Doppler ultrasound
      in early stage cerebral arteriosclerosis. METHODS: We selected 50 patients with
      early cerebral arteriosclerosis as the disease group. At the same time we
      selected another 50 patients as a control group with no significant symptoms in
      the nervous system. By 2 MHz pulse Doppler probe through double-temporal windows
      and pillow windows Basilar artery (BA), the bilateral middle cerebral artery
      (MCA) was detected. In the TCD spectrum, we selected the spectrum of a single
      family cardiac cycle, identified the starting point (ts), pulse-incisure point
      (ti), end point (te), and the peak velocity (tp), measured the time of the
      spectrum starting point to the peak velocity (Tp) and calculated the time
      required for the peak velocity in the share of ventricular systolic (Tp/Ti), the
      time required for the peak velocity in the share of the whole cardiac cycle
      (Tp/T). Tp, Tp/Ti and Tp/T were respectively named as time to peak velocity
      (TPV), peak-time index-1 (PTI-1) and peak-time index-2 (PTI-2). All data were
      analyzed by SPSS13.0. RESULTS: There was no significant difference in blood
      vessel velocity, PI, RI and S/D of BA and RMCA (P>0.05) between the control group
      and the disease group. Compared with the control group, TPV of the BA, LMCA and
      RMCA significantly extended, PTI-1 and PTI-2 of BA, LMCA and RMCA increased
      significantly in the disease group (P<0.01). In the disease group, there was no
      significant correlation between peak time index and PI, S/D (P>0.05). CONCLUSION:
      TPV, PTI-1 and PTI-2 are sensitive indicators of early stage cerebral
      arteriosclerosis.

PMID- 22659664
TI  - [Correlation between C-reactive protein and pain in periprosthetic infection
      after total hip arthroplasty].
AB  - OBJECTIVE: To explore the difference in level of pain experienced by patients
      with total hip arthroplasty between aseptic loosening and periprosthetic
      infection, and to examine the correlation between C-reactive protein (CRP) and
      pain. METHODS: Fifty-one patients (recruited from our hospital between March 2010
      and November 2011) suffering aseptic loosening or periprosthetic infection after
      total hip arthroplasty were included in this study: 24 males and 27 females, with
      mean age 68.13 years. The patients were divided into an aseptic loosening group
      (n=31) and a periprosthetic infection group (n=20). Both the visual analog scale
      (VAS) and Harris pain score were used to estimate the level of pain experienced
      by the patients. CRP levels in serum were measured. The difference in assessment
      of pain by VAS and Harris pain score was compared between the two groups, and the
      correlation between pain and CRP was analyzed. RESULTS: The mean VAS in the
      aseptic loosening group was 5.39 (2.10-8.13) compared with 5.48 (2.09-8.30) in
      the periprosthetic infection group; however, the difference was not statistically
      significant (P=0.85). The mean rank of Harris pain score was 26.23 in the aseptic
      loosening group and 25.65 in the periprosthetic infection group, but again there
      was no significant difference (P=0.88). The CRP level in the periprosthetic
      infection group (36.20-101.40 mg/L, mean 72.86 mg/L) was obvious higher than that
      in the aseptic loosening group (1.37-13.70 mg/L, mean 6.53 mg/L), and the
      difference was statistically significant (P<0.01). The VAS was related with the
      CRP level in the periprosthetic infection group (r=0.87, P<0.01), and the
      correlation between Harris pain score and CRP level was conspicuous (r=0.92,
      P<0.01) in this group. However, those correlations were not evident in the
      aseptic loosening group (r=0.25, P=0.17; r=0.19, P=0.65). CONCLUSION: There is no
      difference in perception of pain in patients after total hip arthroplasty between
      those with aseptic loosening and those with periprosthetic infection. It is
      therefore unreliable to make a initial diagnosis only according to the level of
      pain. However, the level of CRP is a sensitive and effective way of
      differentiating the two conditions. The positive correlation between CRP and pian
      exists in patients with periprosthetic infection but not with aseptic loosening.

PMID- 22659665
TI  - [Posterior open-door laminoplasty combined with lateral mass plate fixation in
      the treatment of ossification of the posterior longitudinal ligament of the
      cervical spine].
AB  - OBJECTIVE: To evaluate the clinical effect of posterior decompression and open
      door laminoplasty combined with lateral mass plate fixation in the treatment of
      ossification of the posterior longitudinal ligament of the cervical spine (OPLL).
      METHODS: A total of 41 OPLL patients in our hospital, with differing extents of
      spinal compression, were analyzed retrospectively. All cases underwent a
      posterior open-door laminoplasty operation, and lateral mass plate fixation. The
      Japanese Orthopedic Association ( JOA) score was adopted to evaluate nerve
      function. RESULTS: All cases were followed up for 12 to 16 (14+/-2.0) months. The
      postoperative JOA score was increased 4.8 points compared with the preoperative.
      CONCLUSION: Posterior open-door laminoplasty combined with lateral mass plate
      fixation for ossification of the posterior longitudinal ligament of the cervical
      spine possesses the advantages of extensive applicability, simplicity and safety,
      and strong stability. It is an efficient and reliable method for ossification of
      the posterior longitudinal ligament.

PMID- 22659666
TI  - [Comparison of endoscopic band ligation and propranolol for the primary
      prophylaxis of variceal bleeding in cirrhosis].
AB  - OBJECTIVE: To compare endoscopic variceal ligation (EVL) with propranolol for
      prophylaxis of first variceal bleeding. METHODS: We chose 168 patients with
      cirrhosis and esophageal varices in our hospital and allocated them to EVL and
      propranolol groups. Treatment effectiveness and safety in the 2 groups were
      observed. RESULTS: he parameters of two groups were similar before therapy.
      Follow-up period was 8-36 months. Variceal bleeding occurred in 24 (28.6%) of the
      EVL group and in 20 (23.9%) of the propranolol group (P>0.05). Overall mortality
      and death related to bleeding were similar (21.4% vs 17.9%; 7.1% vs 6.0%,
      P>0.05). Adverse events related to EVL were 43 (3 of them life-threatening)
      compared to 16 in the propranolol group (51.19% vs 19.05%, P<0.05). CONCLUSION:
      Propranolol may be the better choice in prophylaxis of variceal bleeding with
      similar effects and lower adverse events than with EVL.

PMID- 22659667
TI  - [Analysis of learning curve of laparoscopic splenectomy].
AB  - OBJECTIVE: To evaluate the surgical outcomes of laparoscopic splenectomy and to
      investigate the learning curve of laparoscopic splenectomy. METHODS: Forty cases
      of laparoscopic splenectomy (performed by W.Y. between September 2008 and August
      2010) in our general surgery department were reviewed, and the cases were divided
      equally into 4 groups (group I, II, III, IV) according the time sequence of the
      operations. The operating time, blood loss, conversion to open surgery,
      conversion to hand-assisted laparoscopic splenectomy, postoperative hospital
      stay, postoperative liquid diet recovery time, intra- and postoperative
      complications and the operative frequency were compared. RESULTS: There were no
      statistical differences among the groups in age and gender (P>0.05). The
      operating time, blood loss and postoperative hospital stay of groups III and IV
      were significantly less than those of groups I and II (P<0 .05). Postoperative
      liquid diet recovery time appear to show a gradual shortening trend from Group I
      to Group IV, but the differences were not at standard statistical thresholds
      (P>0.05). Frequency of conversion to open surgery, of conversion to hand-assisted
      laparoscopic splenectomy, of complications among the four groups were also not
      statistically different (P>0.05). The operative frequency of group I-IV increased
      from 1.25/month to 2.5/month. CONCLUSION: The learning curve of laparoscopic
      splenectomy for surgeon who was experienced in open splenectomy and laparoscope
      cholecystectomy is approximately 20 cases, and the operative frequency is about
      1.33/month.

PMID- 22659668
TI  - [Analyses of cosmetic sanitary quality in Hunan Province in 2010].
AB  - OBJECTIVE: To establish a scientific foundation for cosmetic supervision and
      administration based on the analysis of the sanitary quality of cosmetics in
      Hunan Province during 2010. METHODS: According to Cosmetic Sanitary Standards
      (set by the Ministry of Health, People's Republic of China), 150 random samples
      of cosmetics in Hunan were assayed both for microbial items (including total
      plate count, fungus and yeast, fecal coliform, staphylococcus aureus, pseudomonas
      aeruginosa) and chemical items (including 17 kinds of prohibited substances and
      14 kinds of restricted substances). RESULTS: The total rate of cosmetics failing
      to meet the standards was 22.0% of the 150 samples; specific rates for failing
      perfumes, skin care products (eye cream) and deodorant products were, relatively,
      70.6%, 60.00%, and 44.4%. Four kinds of prohibited substances, including diethyl
      phthalate, acrylamide, asbestos and neodymium, as well as 2 kinds of restricted
      substances, including triclosan and formaldehyde, were found to exceed standards.
      None of microbial items exceeded standard levels. CONCLUSION: The sanitary
      quality control of cosmetics is lax. Administrative departments should not only
      reinforce their post-production supervision with respect to cosmetics, but also
      consolidate their control over the process of cosmetic production in order to
      solve the problem of toxic residues or illegal and intentional adulterations.

PMID- 22659669
TI  - [A comprehensive evaluation of the health services in Hunan Province].
AB  - OBJECTIVE: To establish a comprehensive evaluation system for the development of
      health services, and to assess the levels of health services in 2008 and 2009 in
      Hunan compared with seven other provinces in central China, so as to provide a
      basis for hygiene management decisions. METHODS: In order to establish a
      comprehensive evaluation system, a Delphi method, a boundary value method, and an
      RSR method were applied, respectively, to survey indices of health service
      development, to screen indices, and to determine index weights. A weighted TOPSIS
      method was used to evaluate the development status of health services of the
      eight provinces. RESULTS: The Cronbach's alpha coefficient of the questionnaire
      was 0.884, indicating a proper surface validity and a content validity. The
      expert positive coefficient, authority coefficient and Kendall coefficient were
      93.75%, 0.8117, and 0.31, respectively. A comprehensive evaluation system, which
      consisted of 3 primary indices, 10 secondary indices and 52 tertiary indices, was
      established. The result of the comprehensive evaluation showed that the health
      services development of Hunan Province ranked 7th and 6th among the 8 central
      provinces for 2008 and 2009, respectively. CONCLUSION: The established,
      comprehensive evaluation system has a high reliability. Health services
      development of Hunan Province is relatively backward among the 8 central
      provinces.

PMID- 22659670
TI  - [Research progress with renalase and cardiovascular disease].
AB  - Renalase, a novel amine oxidase, is secreted by kidney. It regulates heart
      function and blood pressure by degrading catecholamines. Hormones secreted by the
      kidney are associated with cardiovascular disease. Renalase, as a new biomarker
      of heart and kidney functional correlation, can lower blood pressure, protect
      ischemic heart muscle, improve heart function and degrade catecholamine.

PMID- 22659671
TI  - [Transfection of BDNF gene promotes bone mesenchymal stem cells to differentiate
      into neuron-like cells].
AB  - OBJECTIVE: To provide further foundation for the therapy for spine cord injury by
      transferred mesenchymal stem cells (MSC) expressing the brain-derived
      neurotrophic factor (BDNF) gene. METHODS: Bone mesenchymal stem cells were
      isolated from rats and directly cultivated and expanded in vitro. Bone
      mesenchymal stem cells were divided into 3 groups: a pEGFP-N1- BDNF-transfected
      group (BDNF group), a pEGFP-N1 transfected group (vector group) and a non
      transfected group. Western blot was applied to detect the expression of
      transgenic bone mesenchymal stem cells. The differentiation of bone mesenchymal
      stem cells was identified by immunofluorescence. The rates of induction of neuron
      like cells among the three cell groups were compared. RESULTS: The cell surface
      markers of bone mesenchymal stem cells included expression of CD90 (+), CD44 (+),
      CD34 (-), CD45 (-). The expression of BDNF in the transfected bone mesenchymal
      stem cells was demonstrated by Western blot. The positive ratio of neuron-like
      differentiation in the BDNF group was higher than that of both the vector group
      and the non-transfected group (P<0.05). CONCLUSION: BDNF gene plays an important
      role in promoting bone marrow mesenchymal stem cells to differentiate into neuron
      like cells.

PMID- 22659672
TI  - [A clinical analysis of 96 patients with bloodstream infections after solid organ
      transplantation].
AB  - OBJECTIVE: To evaluate clinical characteristics, pathogens, treatment regimens
      and outcomes in patients with bloodstream infections (BSIs) after solid organ
      transplantation. METHODS: Clinical data of ninety six cases of BSI were analyzed
      retrospectively to identify the pathogens and the origin of infection, and to
      evaluate comprehensive treatment and the causes of success or failure. RESULTS:
      All 96 patients underwent the comprehensive treatments, including suspending
      administration of immunosuppressants and starting administration of appropriate
      antibiotics. The clinical characteristics of patients with BSIs after solid organ
      transplantation were atypical. The pathogens were various and seriously multi
      drug resistant, which led to a high mortality. Among them 57 cases recovered, but
      the BSI-related mortality rate was 40.6%. CONCLUSION: Stopping the administration
      of immunosuppressants, reasonable use of antibiotics, nutritional support and
      protecting the function of organs as soon as possible were of the greatest
      importance among of the various treatment plan. Avoidance of all kinds of
      infection in the first place is most important.

PMID- 22659673
TI  - Ab initio Hartree-Fock and density functional theory investigations on the
      conformational stability, molecular structure and vibrational spectra of 5-chloro
      3-(2-(4-methylpiperazin-1-yl)-2-oxoethyl)benzo[d]thiazol-2(3H)-one drug molecule.
AB  - In this work, the experimental and theoretical spectra of 5-chloro-3-(2-(4
      methylpiperazin-1-yl)-2-oxoethyl)benzo[d]thiazol-2(3H)-one molecule (abbreviated
      as 5CMOT) are studied. The molecular geometry and vibrational frequencies are
      calculated in the ground state of molecule using ab initio Hartree-Fock (HF) and
      Density Function Theory (DFT) methods with 6-311++G(d,p), 6-31G++(d,p), 6
      31G(d,p), 6-31G(d) and 6-31G basis sets. Three staggered stable conformers were
      observed on the torsional potential energy surfaces. The complete assignments
      were performed on the basis of the total energy distribution (TED) of the
      vibrational modes calculated. The comparison of the theoretical and experimental
      geometries of the title compound indicated that the X-ray parameters fairly well
      agree with the theoretically obtained values for the most stable conformer. The
      theoretical results showed an excellent agreement with the experimental values.
      The calculated HOMO and LUMO energies show that the charge transfer occurs within
      the molecule.

PMID- 22659674
TI  - A stochastic model for DNA translocation through an electropore.
AB  - A 1D Fokker-Planck simulation of DNA translocation through an electropore under
      finite pulses is presented. This study is motivated by applications relevant to
      DNA electrotransfer into biological cells via electroporation. The results review
      important insights. The translocation may occur on two disparate time scales, the
      electrophoretic time (~ms), and the diffusive time (~s), depending on the pulse
      length. Furthermore, a power-law correlation is observed, F
      PST~(V(m)t(p))(a)/N(b), where F-PST is the final probability of successful
      translocation, V(m) is the transmembrane potential, t(p) is the pulse length, and
      N is the DNA length in segments. The values for a and b are close to 1 and 1.5,
      respectively. The simulated results are compared with previous data to interpret
      the trends. In particular, the diffusive time scale is used to explain the
      frequency dependence observed in electroporation experiments with uni- and bi
      polar pulse trains. The predictions from the current model can be harnessed to
      help design experiments for the further understanding and quantification of DNA
      electrotransfer.

PMID- 22659676
TI  - Role of lipid ordered/disordered phase coexistence in pulmonary surfactant
      function.
AB  - The respiratory epithelium has evolved to produce a complicated network of
      extracellular membranes that are essential for breathing and, ultimately,
      survival. Surfactant membranes form a stable monolayer at the air-liquid
      interface with bilayer structures attached to it. By reducing the surface tension
      at the air-liquid interface, surfactant stabilizes the lung against collapse and
      facilitates inflation. The special composition of surfactant membranes results in
      the coexistence of two distinct micrometer-sized ordered/disordered phases
      maintained up to physiological temperatures. Phase coexistence might facilitate
      monolayer folding to form three-dimensional structures during exhalation and
      hence allow the film to attain minimal surface tension. These folded structures
      may act as a membrane reserve and attenuate the increase in membrane tension
      during inspiration. The present review summarizes what is known of
      ordered/disordered lipid phase coexistence in lung surfactant, paying attention
      to the possible role played by domain boundaries in the monolayer-to-multilayer
      transition, and the correlations of biophysical inactivation of pulmonary
      surfactant with alterations in phase coexistence.

PMID- 22659680
TI  - Allo-SCT for high-risk AML-CR1 in the molecular era: impact of FLT3/ITD outweighs
      the conventional markers.
AB  - Seventy-nine patients with AML in CR1 received allo-SCT between May 2006 and May
      2011, and the prognostic impact of FMS-like tyrosine kinase 3/internal tandem
      duplication (FLT3/ITD) mutation was evaluated in the context of other clinical
      prognostic factors. Patients with FLT3/ITD + AML had significantly inferior DFS
      (2-year DFS: 19% vs 64%, P = 0.0027), increased risk of relapse (1-year: 59% vs
      19%, P = 0.01), and a trend towards decreased OS (P = 0.08) compared with
      patients without FLT3/ITD. Multivariate analysis confirmed FLT3/ITD +
      independently predicted a shorter DFS (HR, 3.0; 95% CI), 1.4-6.5; P = 0.01) and
      increased risk of relapse (HR, 4.9; 95% CI, 2.0-12.3, P = 0.01). Time to relapse
      in patients with FLT3/ITD + was short with 100-day cumulative risk of 45% (95%
      CI, 33-57). Our data suggest that the poor prognostic implication of FLT3/ITD
      positivity remains even after early allo-SCT in patients with FLT3/ITD + AML, and
      patients remain at high risk of early relapse. FLT3/ITD positivity also outweighs
      other conventional prognostic markers in predicting relapse.

PMID- 22659679
TI  - Possible involvement of cytokines, chemokines and chemokine receptors in the
      initiation and progression of chronic GVHD.
AB  - Chronic GVHD (cGVHD) after allogeneic hematopoietic SCT (HSCT) is characterized
      by an infiltration of T cells into target organs including the oral mucosa and
      salivary glands. This study was designed to clarify the molecular mechanism of
      the local accumulation of pathogenic T cells in cGVHD. The expression of
      cytokines, chemokines and chemokine receptors in the buccal mucosa (BM), labial
      salivary glands (LSG) and PBMC from 16 patients with cGVHD after allogeneic HSCT
      was examined. The mRNA expression of T helper 1 (Th1) and Th2 cytokines, and
      several chemokines and chemokine receptors was significantly increased in the BM
      and LSG from cGVHD patients, in comparison with both those in the BM and LSG from
      controls, respectively, and also with those in the PBMC from cGVHD patients.
      Furthermore, the mRNA expression of Th2 cytokines, macrophage-derived chemokine
      and CC chemokine receptor 4 was closely associated with a strong T-cell
      infiltration in the BM and LSG from cGVHD patients. These results suggest that
      cGVHD might be initiated and/or maintained by Th1/Th0 cells and thereafter
      progresses in association with Th2 cell accumulation via the interaction of
      particular chemokine and chemokine receptors.

PMID- 22659681
TI  - Higher angiopoietin-2 and VEGF levels predict shorter EFS and increased non
      relapse mortality after pediatric hematopoietic SCT.
AB  - The roles of angiogenesis and angiogenic factors after allogenic hematopoietic
      SCT (HSCT) and during acute GVHD (aGVHD) are not known. Studies on pediatric
      patients are extremely scarce. Levels of angiopoietin-2 (Ang2) and vascular
      endothelial growth factor (VEGF) were analyzed from blood samples of 67
      consecutive patients. The levels were correlated with aGVHD grades, routine
      laboratory parameters and outcome. Pre-transplant Ang2 values correlated with the
      occurrence of intestinal aGVHD (P=0.009), whereas post-transplant measurements
      correlated with the severity of skin and liver aGVHD (P=0.03, P=0.04,
      respectively). Pre-transplant levels of VEGF were associated with the occurrence
      of skin aGVHD (P=0.04), whereas post-transplant levels correlated to the severity
      of intestinal aGVHD (P=0.04). High Ang2 levels were associated with shorter EFS
      (P=0.039) and increased non-relapse mortality (NRM) (P=0.009). In conclusion,
      higher Ang2 levels predict higher NRM and, with coexisting high VEGF, also
      shorter EFS after pediatric HSCT. Our results suggest that both pre- and post
      transplant levels of Ang2 and VEGF seem to correlate to the clinical state of the
      patient. However, the pathophysiology of this connection needs further studies.

PMID- 22659675
TI  - Gap junction-mediated electrical transmission: regulatory mechanisms and
      plasticity.
AB  - The term synapse applies to cellular specializations that articulate the
      processing of information within neural circuits by providing a mechanism for the
      transfer of information between two different neurons. There are two main
      modalities of synaptic transmission: chemical and electrical. While most efforts
      have been dedicated to the understanding of the properties and modifiability of
      chemical transmission, less is still known regarding the plastic properties of
      electrical synapses, whose structural correlate is the gap junction. A wealth of
      data indicates that, rather than passive intercellular channels, electrical
      synapses are more dynamic and modifiable than was generally perceived. This
      article will discuss the factors determining the strength of electrical
      transmission and review current evidence demonstrating its dynamic properties.
      Like their chemical counterparts, electrical synapses can also be plastic and
      modifiable. This article is part of a Special Issue entitled: The Communicating
      junctions, roles and dysfunctions.

PMID- 22659682
TI  - Successful hematopoietic cell transplantation in a child with sickle cell disease
      and systemic lupus erythematosus.

PMID- 22659683
TI  - Relative recovery of haematopoietic stem cell products after cryogenic storage of
      up to 19 years.
AB  - There is an increasing trend towards long-term frozen storage of haematopoietic
      stem cells. For such stem cells, harvested from peripheral blood (PB) or BM, it
      is not known if stem cell viability decreases with time. In this study, 31
      separate bags of stem cell product (SCP) stored for 11-19 years (median 15 years)
      were assessed for total nucleated cell (TNC) count, colony forming unit
      granulocyte/macrophage (CFU-GM), CD34+ cell count and cell viability. The results
      were compared with the initial results obtained for the products at the time of
      stem cell harvest, and the percentage recovery of each parameter was plotted
      against time. Recovery of TNC, CD34+ cell count and cell viability decreased with
      time (P=<0.01) but CFU-GM did not. This study shows that SCPs harvested from PB
      and BM do deteriorate with long-term storage. This could have an impact on rates
      of engraftment.

PMID- 22659684
TI  - Anti-thymocyte globulins capable of binding to T and B cells reduce graft-vs-host
      disease without increasing relapse.
AB  - Anti-thymocyte globulin (ATG) is polyclonal, containing Ab specificities capable
      of binding to various immune-cell subsets implicated in the pathogenesis of GVHD,
      including T cells, B cells, natural killer cells, monocytes/macrophages,
      neutrophils and DC. We wished to determine which ATG specificities are important
      for GVHD prevention. We measured day 7 serum levels of 23 ATG specificities in
      120 hematopoietic cell transplant recipients whose myeloablative conditioning
      included 4.5 mg/kg ATG (thymoglobulin). High levels of ATG specificities capable
      of binding to T- and B-cell subsets were associated with a low likelihood of
      acute GVHD (aGVHD). High levels of these ATG specificities were associated with
      increased rates of viral but not bacterial or fungal infections. They were not
      associated with an increased risk of malignancy relapse; on the contrary, high
      levels of ATG specificities capable of binding to regulatory T cells and
      invariant NKT cells were associated with a low risk of relapse. In conclusion,
      high levels of ATG antibodies to Ag(s) expressed on T and B cells are associated
      with a low risk of aGVHD and a high risk of viral but not bacterial or fungal
      infections. These antibodies have neutral or beneficial effects on relapse.

PMID- 22659685
TI  - Portable microstimulator for chronic deep brain stimulation in freely moving
      rats.
AB  - In the last decades, deep brain stimulation (DBS) has been widely used as a
      functional surgical strategy for the treatment of a variety of neurological and
      psychiatric disorders, including Parkinson's disease (PD), dystonia, epilepsy,
      depression or obsessive-compulsive disorder. While the therapeutic benefits of
      DBS are now recognized, experimental data on its mechanisms and impact at long
      term remain poor. This is mainly due to the lack of a microstimulation system
      adapted for chronic DBS in small laboratory animals. In this context, we have
      developed a microstimulator for DBS adapted to rat. This device, which has a size
      and weight compatible for use in freely moving rat, can be clipped to a support
      fixed on the animal's head. This easy "removal" property is crucial because it
      enables removing or even switching the microstimulator during the experiments
      without having to anaesthetize or to operate the animal, thus minimizing stress.
      The design of the microstimulator allows to set the DBS parameters easily
      (intensity, frequency and pulse width) and to replace the battery for long-term
      DBS. To validate our device, we performed continuous DBS of the subthalamic
      nucleus (known to improve motor deficits in clinic) in a classical rat model of
      PD during 5 weeks. We show that this long duration stimulation reduces
      significantly PD-induced akinesia without inducing animal discomfort and tissue
      damage. These first data demonstrated that long term DBS procedure in behaving
      rat is now workable.

PMID- 22659686
TI  - Chiral nematic organo-siloxane oligopodes based on an axially chiral
      binaphthalene core.
AB  - The synthesis of a novel class of organosiloxane oligopodes, based on an axially
      chiral binaphthalene core is described and their mesogenic properties are fully
      characterised.

PMID- 22659691
TI  - Flicker downregulates the content of crystallin proteins in form-deprived C57BL/6
      mouse retina.
AB  - Image degradation by loss of higher spatial frequencies causes form-deprivation
      myopia (FDM) in humans and animals, and cyclical illumination (flicker) at
      certain frequencies may prevent FDM. The molecular mechanisms underlying FDM and
      its prevention by flicker are poorly known. To understand them better, we have
      identified proteins that differ in amount in form-deprived (FD) mouse retinas,
      under steady versus flickering light. Male C57BL/6 mice (age 27-29 days) were
      randomly divided into three groups: Experimental - monocularly form-deprived, and
      kept under either normal room light ("FD-Only") or 20 Hz flickering light ("FD
      Flicker"), throughout the 12-hour light phase; and Control ("Open-Control") -
      kept under normal illumination, without form deprivation. After two weeks of
      treatment, retinal proteins were extracted and separated by two-dimensional gel
      electrophoresis (2D-GE); proteins that differ in content in FD-only versus FD
      flicker retinas were identified by mass spectroscopy ("MS"), and their identities
      were verified by western blotting. The contents of three identified proteins
      differed statistically in FD-only compared to FD-flicker retinas. These proteins
      were identified by MS as alpha-A-crystallin, crystallin beta A2 and crystallin
      beta A1. Quantitative western blotting showed that the relative amount of alpha-A
      crystallin in FD-only retinas was significantly higher than that in FD-Flicker
      and control retinas. In conclusion, form deprivation induced significant
      increases in the amounts of crystallins in mouse retinas. These increases were
      significantly reduced by exposure to 20 Hz flicker. Since form deprivation is
      known to induce myopia development, and flicker to prevent it, our data suggest
      that FD- and flicker-responsive changes in the content of crystallin proteins may
      be involved causally or protectively in myopia development.

PMID- 22659693
TI  - The complete mitochondrial genome of Pauropus longiramus (Myriapoda: Pauropoda):
      implications on early diversification of the myriapods revealed from comparative
      analysis.
AB  - Myriapods are among the earliest arthropods and may have evolved to become part
      of the terrestrial biota more than 400 million years ago. A noticeable lack of
      mitochondrial genome data from Pauropoda hampers phylogenetic and evolutionary
      studies within the subphylum Myriapoda. We sequenced the first complete
      mitochondrial genome of a microscopic pauropod, Pauropus longiramus (Arthropoda:
      Myriapoda), and conducted comprehensive mitogenomic analyses across the
      Myriapoda. The pauropod mitochondrial genome is a circular molecule of 14,487 bp
      long and contains the entire set of thirty-seven genes. Frequent intergenic
      overlaps occurred between adjacent tRNAs, and between tRNA and protein-coding
      genes. This is the first example of a mitochondrial genome with multiple
      intergenic overlaps and reveals a strategy for arthropods to effectively compact
      the mitochondrial genome by overlapping and truncating tRNA genes with neighbor
      genes, instead of only truncating tRNAs. Phylogenetic analyses based on protein
      coding genes provide strong evidence that the sister group of Pauropoda is
      Symphyla. Additionally, approximately unbiased (AU) tests strongly support the
      Progoneata and confirm the basal position of Chilopoda in Myriapoda. This study
      provides an estimation of myriapod origins around 555 Ma (95% CI: 444-704 Ma) and
      this date is comparable with that of the Cambrian explosion and candidate
      myriapod-like fossils. A new time-scale suggests that deep radiations during
      early myriapod diversification occurred at least three times, not once as
      previously proposed. A Carboniferous origin of pauropods is congruent with the
      idea that these taxa are derived, rather than basal, progoneatans.

PMID- 22659694
TI  - Bi-directional PCR allele-specific amplification (bi-PASA) for detection of
      caspase-8 -652 6N ins/del promoter polymorphism (rs3834129) in breast cancer.
AB  - Caspase-8 (CASP8) plays a critical role in regulating apoptosis, and its
      functional polymorphisms may modify cancer risk. We investigated the possible
      association between CASP8 -652 6N ins/del (rs3834129) and the risk of breast
      cancer in a sample of Iranian population. This case-control study was done on 236
      breast cancer patients and 203 cancer free healthy female. We designed a rapid
      and simple bi-directional PCR allele-specific amplification (bi-PASA) for
      detection of CASP8 -652 6N ins/del polymorphism. The results showed that the
      CASP8 -652 6N del/dl genotype was inversely associated with breast cancer risk
      (OR=0.33, 95% CI=0.17-0.65, p=0.001). The frequencies of the del allele in cases
      and controls were 29.1% and 38.6%, respectively. An inverse association between
      CASP8 6N del variant and the risk of breast cancer (OR=0.66, 95% CI=0.66-0.87,
      p=0.002) was found. In conclusion, the result suggests that the CASP8 -652 6N del
      polymorphism plays a protective role in susceptibility to breast cancer in our
      population. Further studies in other populations with larger samples are needed
      to confirm these findings.

PMID- 22659695
TI  - The ethics of live patient use in dental hygiene clinical licensure examinations:
      a national survey.
AB  - A national survey of dental hygienists was conducted to explore ethical issues
      arising from the use of live patients for dental hygiene clinical licensure
      examinations. Data were collected regarding respondents' demographics, additional
      costs they incurred associated with their examination beyond the examination
      fees, delays in patients' treatment resulting from the examination, unethical
      candidate and/or patient behaviors they experienced, and provisions they made for
      patients' follow-up care related to the examination. Five hundred surveys were
      mailed to dental hygienists from two states in each of the five licensure
      examination regions. The response rate was 40.6 percent (n=203). Descriptive
      statistics were used to analyze the data. The results showed that the majority of
      the respondents spent additional money on examination-related expenses (69.2
      percent). Sixty-one percent of the respondents reported paying their patients;
      however, only 50.5 percent felt such a practice was acceptable. More than half
      (53.1 percent) reported believing it was appropriate to delay treatment in order
      to have a patient participate in the examination, although only 16.4 percent
      reported actually delaying treatment. Informed consent was said to be obtained by
      94.9 percent of the respondents. The majority (86.6 percent) said they referred
      patients for follow-up dental hygiene care. When asked if they felt the
      examination was an accurate assessment of their clinical skills, 78.7 percent of
      the respondents agreed that it was.

PMID- 22659696
TI  - Dental hygienists' knowledge and opinions of oral-systemic connections:
      implications for education.
AB  - Although associations between periodontal and systemic health have been well
      established, there is little evidence regarding dental hygienists' knowledge of
      the oral-systemic connection. The purpose of this study was to determine the
      knowledge levels of North Carolina dental hygienists regarding oral-systemic
      connections and their attitudes and confidence about incorporating this knowledge
      into clinical practice. A survey was developed, pilot tested, revised, and mailed
      to 1,665 licensed dental hygienists in North Carolina. After three mailings, the
      response rate was 62 percent, with 52 percent (N=859) meeting the inclusion
      criteria. The majority (>80 percent) of the respondents correctly identified risk
      factors for diabetes and cardiovascular disease (CVD), but were less
      knowledgeable about risk factors for osteoporosis and adverse pregnancy outcomes.
      Most knew that there is strong evidence linking periodontal disease with CVD (77
      percent) and diabetes (70 percent). The majority felt that dental hygienists
      should be trained to identify risk factors for oral-systemic disease (94 percent)
      and to actively manage patients with systemic disease (78 percent). Eighty-eight
      percent felt that dental and medical professionals should be taught to practice
      collaboratively. These dental hygienists had a high level of knowledge in some
      areas of oral-systemic disease but could improve their confidence levels and
      knowledge through expanded content in their educational programs and continuing
      education. Inter-professional education and collaboration would also assist in
      integration of knowledge into clinical practice.

PMID- 22659697
TI  - Consumers' choice of dentists: how and why people choose dental school faculty
      members as their oral health care providers.
AB  - This study aimed to better understand how and why people choose dental school
      faculty members as their oral health care providers. Increasing financial
      constraints in U.S. dental schools have led their administrators to seek
      alternative funding sources, one of which can be revenues from dental school
      faculty practice. To effectively promote faculty practice, it is necessary to
      understand how and why one chooses a dental school faculty member as his or her
      oral health care provider. A survey of 1,150 dental school faculty practice
      patients who recently chose their dentist was conducted, and 221 responded. The
      information sources these respondents said they used and rated highly were other
      dentists, friends, family members, clinic website, the Internet, and the
      insurance directory. Dentist-related attributes that were perceived to be
      important were quality of care, professional competence of dentist, and
      explanation of treatment/patient participation in the treatment decision. Dental
      practice-related attributes perceived to be important were the ability to get
      appointments at convenient times, reasonable waiting time to get appointments,
      and attitude/helpfulness of staff. This study found that traditionally popular
      (family, friends) and newly emerging information sources (the Internet, clinic
      website, and insurance directory) were both used and perceived to be important by
      patients of the dental school faculty practice. Dental schools and dentists can
      use this study's findings to select appropriate communication channels to promote
      their practices and to focus on attributes that dental consumers value the most.

PMID- 22659698
TI  - Evaluation of postgraduate dental specialty residents: a survey of program
      directors.
AB  - The professional dental literature is lacking in information concerning the use
      of technology in evaluation procedures utilized in postgraduate dental education.
      The purpose of this study was to identify the methods of evaluation of U.S.
      postgraduate specialty residents currently in place. The study also sought to
      determine if there were any patterns among programs more likely to utilize
      electronic submission in the evaluation process. An electronic survey consisting
      of eighteen questions was sent to the program directors of all accredited U.S.
      dental specialty programs (n=416). The survey yielded 150 responses, for a 36
      percent response rate. The results showed that the majority of responding program
      directors (68 percent) evaluate their residents using a hardcopy evaluation
      instrument, while a minority of directors (32 percent) reported using an
      electronic evaluation instrument. The majority of respondents (58 percent) said
      they require faculty members to formally evaluate residents semiannually. Fifty
      percent of responding program directors reported a need for improvement in their
      current evaluation system. Those reporting a need for improvement were less
      likely to be using an electronic format. There was no statistical significance
      between faculty responsiveness and the mode of evaluation used. With many program
      directors reporting room for improvement in their current evaluation system,
      innovation in the evaluation systems of postgraduate dental education is needed.

PMID- 22659699
TI  - Where is leadership training being taught in U.S. dental schools?
AB  - Since leadership is vital in all professions and organizations, the purpose of
      this study was to determine where in dental schools leadership for predoctoral
      students is taught and to what degree it is emphasized in order to establish a
      baseline from which to generate recommendations for best practices. Academic
      deans of U.S. dental schools were surveyed to determine where in the curriculum
      leadership is taught and emphasized. The response rate was 39 percent returned
      completed surveys. These responses were representative of all geographic regions
      of the country, with equitable distribution between private and public
      institutions. The results showed that leadership training is delivered in many
      different parts of the curriculum and at various levels. Generally, the
      respondents indicated that leadership education is delivered in the setting of
      practice management, community out-reach, or public health. In some cases,
      specific training programs are dedicated to leadership development. Thus, several
      models for leadership development were identified, showing design flexibility in
      addressing regional and national needs. In the future, it would be of value to
      assess the effectiveness of the various models and whether single or multiple
      pathways for leadership training are most beneficial.

PMID- 22659700
TI  - Increasing student diversity and cultural competence as part of Loma Linda
      University School of Dentistry's service mission.
AB  - For many years, studies have identified a need for greater racial and ethnic
      diversity among dental professionals. However, the ability of the field to
      collectively address the problem has been hindered by the low numbers of
      underrepresented minority students who apply to dental school. Over the past two
      decades, college attendance rates have increased and U.S. dental school
      applications have tripled, but the number of underrepresented minority dental
      applicants has remained about the same. With the increasing diversity of the U.S.
      population and specifically that of the state of California, the dental workforce
      would be enhanced by the presence of more underrepresented minority dentists.
      Additionally, curricular changes should be implemented to better prepare dental
      students to meet the oral health care needs of diverse populations. There is
      general agreement that these workforce and curricular changes would enhance
      access to care for underserved populations. For seven years, Loma Linda
      University School of Dentistry participated in the Pipeline, Profession, and
      Practice: Community-Based Dental Education program. The first phase of this
      national program addressed deficiencies in diversity in dentistry and in access
      to oral health care. In the second phase, Loma Linda University continued to
      collaborate with other California dental schools on specific state initiatives.
      This article provides an overview of the school's efforts to enroll a more
      diverse student body, enhance all its students' cultural competence, and expand
      care to underserved populations.

PMID- 22659701
TI  - Electronic vs. traditional textbook use: dental students' perceptions and study
      habits.
AB  - This descriptive study assessed dental students' attitudes about computer use as
      it relates to study habits and use of e-textbook technology. Academic deans and
      student leaders at all accredited dental education programs in the United States,
      Puerto Rico, and Canada were asked to forward an e-mail to students explaining
      the purpose of the study and asking them to participate. The e-mail included an
      embedded URL link to the survey. A total of 703 complete responses from twenty
      four dental schools were received and used in the final analysis. Because the
      number of students contacted could not be determined, the overall response rate
      cannot be calculated. Over 65 percent of the respondents reported spending >11
      hours per week studying although over 75 percent said they spent little time
      studying from their textbooks. Over 55 percent were from schools that use e
      textbooks exclusively, with 25 percent from schools that exclusively use print
      textbooks. One-fourth indicated they purchased a traditional printed textbook
      even when an e-textbook was provided; more than one-third printed information
      from the e-textbooks rather than reading on the computer. A majority (59 percent)
      preferred traditional textbook resources over e-textbooks, with over 50 percent
      reporting not using the required e-textbooks at all. E-textbooks were used by
      students in this study less frequently than materials/notes provided by dental
      school faculty. The majority preferred to use traditional resources as references
      and for augmenting lecture material.

PMID- 22659702
TI  - Effectiveness of training dental students in two occlusal indices.
AB  - The purpose of this study was to evaluate the ability of students in a U.S.
      dental school to learn and apply two indices of orthodontic need: the Index of
      Orthodontic Treatment Need (IOTN) and the Index of Complexity, Outcome, and Need
      (ICON). Dental students were randomly selected and separated into three groups:
      control, IOTN, and ICON. Each evaluated thirty casts that had previously been
      evaluated by a panel of thirteen orthodontists to develop a gold standard of
      orthodontic treatment need for these casts. Students re-evaluated the same thirty
      casts after IOTN and ICON training for their own group, while the control group
      did not receive any training. Logistic regression of pre- and post-training
      agreement with the gold standard was calculated for each group to create a clear
      quadratic relationship. Significant differences were not found between pre- and
      post-training evaluation for either the IOTN or the ICON groups as compared to
      the control. However, the IOTN group did show more improvement when compared with
      the ICON group. This study demonstrates that the use of the IOTN index improved
      assessment in predoctoral dental students to determine orthodontic treatment
      need.

PMID- 22659703
TI  - Dental and medical students' perspectives on early exposure to PBL in Taiwan.
AB  - A hybrid problem-based learning (PBL) curriculum adopted in 2002 for medical
      students at China Medical University, Taiwan, was extended to dental students in
      2007. Before that, PBL workshops were conducted for all students. Two PBL cases
      on basic biomedical issues were used for second-year medical students and second
      year dental students to explore the feasibility of adopting PBL as part of the
      dental curriculum. This study compared the medical and dental students' attitudes
      toward the PBL tutorials and PBL curricula. Upon completion of the PBL component,
      an eighteen-item questionnaire asked students to assess (on a ten-point scale
      with 10 as the most positive response) their perceptions of the learning process
      in the PBL tutorials. Forty-six dental students from a cohort of fifty (92
      percent) and 107 medical students from a cohort of 119 (90 percent) completed the
      questionnaires (fifty-three females and 100 males). The importance of all items
      was rated above 6.00. The medical students' mean score (7.29) was higher than the
      dental students' mean score (7.10). Of the eighteen attributes of the PBL
      process, the students indicated being generally comfortable with fourteen. No
      statistical significance was found between the dental and medical students'
      scores, but there was a significant difference (p=0.006) in their perception of
      PBL curricula. Overall, the medical students expressed a more positive outlook
      toward the PBL learning process than the dental students and were more willing to
      accept PBL as a pedagogy.

PMID- 22659704
TI  - The status of mineral trioxide aggregate in endodontics education in dental
      schools in Turkey.
AB  - The aim of this study was to assess the current status of mineral trioxide
      aggregate (MTA) as an educational material in dental schools in Turkey. A survey
      was sent to senior members of the endodontic departments of seventeen dental
      schools; fourteen responded. All respondents reported that they used MTA in their
      clinical practice, with apexification, perforations, retrograde fillings, and
      root resorptions being the most frequently occurring treatment procedures. All
      reported that information was given to students regarding MTA mainly as part of
      the curriculum. The third and fourth years were the periods when MTA was
      introduced to students in most of the schools. Twelve schools reported that
      students had the opportunity to observe procedures in which MTA was used, but
      students had the chance to use the material in a very minor proportion of the
      schools, mainly under the supervision of clinical instructors. Ten schools agreed
      that MTA should be included in the regular endodontic curriculum. Financial
      constraints seemed to be the predominant reason for those who answered this
      question negatively, followed by difficult handling properties and low
      radiopacity of the material. Within the limitations of this study, it can be
      concluded that ways should be sought to prevent financial difficulties from
      depriving dental students of the opportunity to receive information about
      contemporary methodologies such as MTA utilization.

PMID- 22659705
TI  - New multipurpose endodontic device developed in Germany for use in predoctoral
      and continuing dental education and science.
AB  - The purpose of this article is to describe a simple and versatile aid for the
      endodontic treatment of extracted teeth and its possible applications. The Med*
      box is a new endodontic multipurpose device made of transparent acrylic that
      permits all elements of root canal treatment to be performed and evaluated either
      visually or radiologically. The Med*-box represents a valuable addition to the
      spectrum of educational and practical means in endodontic training. It is well
      suited for students, dentists, and endodontists for learning the handling of new
      materials, methods, and instruments in endodontics before they work clinically
      upon a patient. Also in the context of scientific endodontic issues, the Med*-box
      represents a simple, economical, and easily manageable aid.

PMID- 22659706
TI  - A brief comparison of curricula at dental schools in China and Japan.
AB  - This study compared the dental curricula at dental schools in China and Japan. A
      survey was conducted in representative dental schools in China and Japan. It was
      found that, in China and Japan where dental schools recruit students directly
      from high schools, more attention is paid to introduction of early professional
      education. Most dental schools in Japan arrange dental subjects for their
      students from the first through the fourth years, while in China, only a few
      dental schools take this path although many of them are currently making changes.
      It was also discovered that, in both countries, an increasing number of dental
      schools assign a specific dental subject to the same period with its relevant
      bioscience or biomedical counterparts, which makes it possible for them to
      enhance each other reciprocally in a positive way for students and consequently
      help dental students master the related topics.

PMID- 22659707
TI  - Factors related to sense of coherence among dental students at Istanbul
      University.
AB  - The salutogenic model suggests that generalized resistance resources (GRRs)
      promote the development and maintenance of a strong sense of coherence (SOC),
      which is a health-promoting factor. This study examined associations between GRRs
      (sociodemographic characteristics, social support, stress, health practices, and
      self-rated health) and a strong SOC among dental students at Istanbul University.
      Data were collected from a convenience sample of 566 students using
      questionnaires including a sociodemographic section, the SOC scale, the Perceived
      Stress Scale, the Multidimensional Scale of Perceived Social Support, self-rated
      health, and health practices. Data were analyzed using descriptive statistics, t
      test, chi-square test, and binary multiple logistic regression. Students were
      classified into a low or strong SOC group by a median split procedure, based on
      their total score on the SOC scale (median=56, range=22 to 91). Univariate
      statistics showed that students with a strong SOC reported lower stress levels,
      higher social support levels, better self-rated health, brushing their teeth more
      frequently, lower sugar intake between meals, and less frequent smoking than
      students with a low SOC. Multivariate statistics indicated that being a nonsmoker
      and having better self-rated health, higher social support levels, lower stress
      levels, and lower sugar intake between meals were the most important predictors
      of strong SOC. Taking into account the factors that reinforce a strong SOC may
      help dental educators develop health promotion programs and create supportive
      environments for maintaining dental students' health.

PMID- 22659708
TI  - Teaching, research, and job satisfaction of prosthodontic faculty members in
      Indian academic dental institutions.
AB  - The aim of this study was to determine prosthodontic faculty members'
      satisfaction with their roles of teaching, research, and service in academic
      dental institutions of India. The head of the prosthodontic department of each
      institution was informed of the study by telephone and asked to invite his or her
      staff members to complete a questionnaire. The questionnaire used a rating scale
      of 1=very dissatisfied, 2=dissatisfied, 3=neutral, 4=satisfied, and 5=very
      satisfied. The satisfaction score for each of the three categories was determined
      by summing the weights for all items related to the variable. In the study, 386
      prosthodontic faculty members from 184 dental institutions were invited to
      participate, and 341 faculty members from 139 dental institutions completed the
      questionnaire. The data obtained were analyzed using statistical software. Most
      of the respondents were satisfied with their teaching and service items. Neutral
      responses were made for institutional teaching rewards, institutional financial
      support for research, release time offered by the institution, support for
      sabbatical leaves, technical assistance in analyzing data, secretarial and
      technical assistance, institutional research rewards, in-service training
      opportunities, and institutional service rewards. Dissatisfied responses were
      made regarding financial and academic support for making scientific presentations
      and attending conferences and seminars.

PMID- 22659709
TI  - Effect of an educational course at an Iranian dental school on students'
      knowledge of and attitudes about HIV/AIDS.
AB  - This study investigated the effects of an educational program designed to improve
      the knowledge and attitudes of senior dental students in an Iranian dental school
      about caring for patients with HIV/AIDS. As part of an extramural program in
      community dentistry, a new educational program about HIV/AIDS was developed at
      Tehran University of Medical Sciences in 2009. The program consisted of two days'
      observation at the Consultation Center for Behavioral Diseases and a one-day
      workshop on infection control. A control group was selected from dental students
      at Shahid Beheshti University of Medical Sciences. Before and after the
      intervention, students in both the intervention and control groups completed a
      questionnaire concerning their knowledge of and attitudes about HIV/AIDS.
      Students in the intervention group also expressed their opinions in a post-test
      questionnaire. An independent sample t-test was used for statistical analysis. In
      the control group, the means of students' knowledge and attitude scores did not
      differ significantly from pre-test to post-test. In the intervention group,
      however, the means of both knowledge and attitude scores on the post-test were
      significantly higher than on the pre-test (p=0.001 and p=0.009, respectively). In
      the intervention group, more than 96 percent of the students reported that they
      would completely follow infection control principles in future practice. This
      study concludes that the educational program improved the students' knowledge of
      and attitudes about HIV/AIDS and will have a positive effect on their future
      practice.

PMID- 22659710
TI  - Demographic profile and future expectations of students enrolled in a Turkish
      private dental school.
AB  - The purposes of this study were to obtain information about the social and
      demographic profile of students enrolled in the first private Turkish dental
      school, to gather information regarding the reasons for their preferences, and to
      obtain data about their career expectations. Questionnaires were distributed to
      278 students; 229 returned the survey for an overall response rate of 82 percent.
      Of the respondents, 145 (65.5 percent) were females and seventy-five (34.5
      percent) were males; they had an average age of 21.62+/-1.58. First degree
      relative (mother, father, sibling) had the greatest influence on the students in
      choosing dentistry as a career. Fathers and mothers had similar impact on the
      students' choice of dental profession (45.9 percent and 46.6 percent,
      respectively). Humanistic feelings, desire to serve others, and reasonable
      working hours were the predominant reasons that motivated females to become a
      dentist (p<0.05). Also, academic interest and interest in a medical field were
      significantly influencing factors for female students (p<0.05 and p=0.001,
      respectively). One-hundred and ninety-seven students (86 percent) expressed a
      goal of specializing in a specific branch of dentistry; orthodontics and oral and
      maxillofacial surgery were the top-ranked specialties. Although only 41 percent
      of the students were of Istanbul origin, 82.5 percent reported that they wish to
      practice in Istanbul.

PMID- 22659711
TI  - A film of rutile TiO2 pillars with well-developed facets on an alpha-Ti substrate
      as a photoelectrode for improved water splitting.
AB  - A photoelectrode of single-crystal rutile TiO(2) pillars with well-developed
      facets shows a 2.5 times higher capability of water splitting at 0.3 V than a
      conventional anatase TiO(2) nanotube array electrode. The improvement is
      attributed to the synergistic effects of the high crystallinity of single-crystal
      rutile pillars, the exposed high-energy {011} and {111} as the reactive facets of
      water oxidation reaction and the extended light absorption range by ca. 23 nm.

PMID- 22659712
TI  - Interrater reliability of ICU EEG research terminology.
AB  - BACKGROUND: Standardized research terminology critical to the establishment of a
      multicenter intensive care unit (ICU) electroencephalogram (EEG) database was
      originally proposed in 2005 and has been modified many times since. However,
      interrater agreement (IRA) of the revised terminology has not been investigated.
      METHODS: After a brief tutorial, investigators of ICU EEG research centers (n =
      16) took an 82-question EEG certification test comprising 10-second EEG samples,
      which assessed the use of main term 1 (pattern location), main term 2 (pattern
      type), and modifiers from the most recently revised terminology. RESULTS: Kappa
      values for main terms 1 and 2 were 0.87 and 0.92, respectively. Agreement was 93%
      for determination of amplitude and 80% for determination of frequency. Kappa
      values for each of the "plus" modifiers (fast, rhythmic, and sharp/spike
      activity) were 0.54, 0.62, and 0.16 respectively. CONCLUSIONS: Main terms 1 and 2
      have high IRA and are reasonable for use in multicenter research. There is a
      suggestion that assessment of amplitude has good reliability, while assessment of
      frequency may have less reliability. The fast and rhythmic "plus" modifiers have
      moderate IRA, while sharp/spike modifier has only slight IRA implying that
      further refinement and assessment of terminology modifiers may be necessary.

PMID- 22659713
TI  - Prognosis of EEG findings in infancy.
AB  - OBJECTIVE: To determine how specific early EEG abnormalities correlate with
      clinical outcome on long-term follow-up for neurological and epilepsy outcomes.
      Our aim was to revisit how early EEG abnormalities should be weighed for
      prognosis. METHODS: This is a retrospective study of 358 infants who had EEGs
      taken between 3 and 12 months of age and subsequent clinical assessment between 4
      to 18 years of age. RESULT: Of the 358 infants, 215 had unfavorable neurological
      outcome (UNO), and 234 had epilepsy on follow-up. Breakdown: 117 had major
      abnormal EEG background of which 86% had UNO and 75% had epilepsy. One hundred
      had abnormal sleep potentials of which 89% had UNO and 80% had epilepsy. One
      hundred seventy-five had interictal epileptiform activity of which 80% had UNO
      and epilepsy. Sixty had ictal epileptiform activity of which 90% had UNO and 86%
      had epilepsy. One hundred ninety-two had markedly abnormal overall EEG impression
      of which 80% had UNO and 79% had epilepsy. CONCLUSIONS: Occurrence of significant
      EEG abnormalities in the first year was clearly associated with UNO and epilepsy.
      Current views that certain EEG abnormalities (e.g., interictal spike) may have
      little prognostic significance would need to be revisited.

PMID- 22659714
TI  - Advanced pharmaco-EEG reveals morphine induced changes in the brain's pain
      network.
AB  - INTRODUCTION: By using a novel brain source modeling approach, where the evoked
      potential (EP) signal was decomposed with multichannel matching pursuit (MMP)
      before source localization, we investigated brain generators of EPs after a pain
      stimulus in the esophagus before and after administration of placebo/morphine. We
      showed that this new approach of pharmaco-electroencephalogram (EEG) analysis can
      shed light on subtle changes, which cannot be foreseen from conventional analysis
      (amplitude/latency/topography). METHODS: In this placebo-controlled crossover
      study, the effects of orally administered morphine (30 mg) on esophageal pain
      elicited by electrical stimulation were investigated in 9 healthy volunteers.
      Using new methods (decomposition of the EPs with MMP and clustering) in
      combination with inverse modeling, we investigated brain sources of the EPs and
      their time-frequency properties. RESULTS: Morphine treatment resulted in a shift
      of the brain sources in the low-frequency range (2-4 Hz) toward the frontal
      cortex during the first 300 milliseconds after stimulus, whereas active brain
      sources after placebo treatment remained stable. CONCLUSIONS: Decomposing the EPs
      into the original brain generators showed that morphine mainly changes the low
      frequency electrical activity in the frontal brain area. This method can be used
      to increase the basic understanding of the opioid effect on the brain's
      processing of pain and eventually identify biomarkers of analgesia in
      experimental pain models.

PMID- 22659715
TI  - How many electromyography channels do we need for facial nerve monitoring?
AB  - PURPOSE: Continuous electromyography (EMG) monitoring is a standard method for
      intraoperative monitoring of facial nerve function. Typically, only two or three
      bipolar channels are recorded from needle electrodes to detect pathologic
      activity, which may provide an incomplete sample. Therefore, we evaluated the
      influence of channel number on monitoring quality. METHODS: The EMG data of 30
      patients undergoing surgery for vestibular schwannoma were recorded using 9
      bipolar channels from subdermal needle electrodes located in the orbicular oculi,
      oris, and nasal muscle. Pathologic A-train activity was evaluated in regard to
      correlation to postoperative nerve function. Channel combinations with different
      channel numbers were compared. RESULTS: A-train quantity showed high correlations
      to postoperative nerve function: Spearman rank correlation of 0.58 for 2, 0.61
      for 3 channels. It increased further with every additional channel to 0.69 for
      all 9 channels (48% of variance accounted for). Single channels with more than
      one-third of total A-train activity ("hot spots") were observed in 17 patients,
      which did not show consistent spatial patterns and could only be completely
      detected with a high number of channels. CONCLUSIONS: Few channels as used in
      conventional monitoring setups yield acceptable results. However, correlation
      between train time and postoperative functional results improves with every
      additional EMG channel.

PMID- 22659716
TI  - Approximate entropy analysis of event-related potentials in patients with early
      vascular dementia.
AB  - This study investigated differences in event-related potential (ERP) parameters
      among early vascular dementia (VD) patients, healthy elder controls (ECs), and
      young controls (YCs). A visual "oddball" color identification task was performed
      while individuals' electroencephalograms (EEGs) were recorded. Approximate
      entropy (ApEn), a nonlinear measure, along with P300 latencies and amplitudes
      were used to analyze ERP data and compare these three groups. The patients with
      VD showed more complex ERP waveforms and higher ApEn values than did ECs while
      performing the visual task. It was further found that patients with VD showed
      reduced P300 amplitudes and increased latencies. The results indicate that
      patients with VD have fewer attention resources to devote to processing stimuli,
      lower speed of stimulus classification, and lower synchrony in their cortical
      activity during the response period. We suggest that ApEn, as a measure of ERP
      complexity, is a promising marker for early diagnosis of VD.

PMID- 22659717
TI  - Short-term effects of electrical stimulation and voluntary activity on
      corticomotor excitability in healthy individuals and people with stroke.
AB  - Electrical stimulation (ES) of muscle is often used to augment motor recovery in
      populations with neurologic disorders. The aim of the study was to examine the
      changes in corticomotor excitability in response to different forms of ES applied
      to the wrist extensors. Healthy adults and people with stroke completed three
      separate test sessions. In each session, 60 wrist extensor contractions were
      elicited by one of the three interventions: (1) voluntary isometric muscle
      activation, (2) automated ES, or (3) electromyography-triggered ES. Motor evoked
      potentials were significantly increased after the voluntary contraction and
      electromyography-triggered ES interventions, but not after automated ES, in
      healthy participants. There was no significant change in motor evoked potential
      amplitude after any of the interventions in the participants with chronic stroke.
      Using the ES parameters of this study, voluntary drive was required to induce
      change in corticomotor excitability in the healthy participants. The stimulation
      intensity and duration parameters used did not induce any immediate changes in
      corticomotor excitability in the participants with stroke. The authors conclude
      that combining voluntary activation with ES may enhance the efficacy of
      stimulation in healthy adults. Repeated applications or longer durations of
      stimulation may be necessary to alter neuronal excitability in a stroke
      population.

PMID- 22659718
TI  - Cortical excitability in migraine and epilepsy:  a common feature?
AB  - OBJECTIVE: There is evidence for comorbidity of migraine and epilepsy. We used
      transcranial magnetic stimulation (TMS) to assess cortical excitability in
      migraine compared with control subjects and patients with epilepsy. METHODS:
      Twenty-six patients drug-naive patients with newly diagnosed migraine were
      studied. These were compared with 19 healthy control subjects and 50 patients
      with new onset epilepsy. Motor threshold (MT) and responses to paired pulse
      stimulation at short (2, 5, 10, and 15 milliseconds) and long (50-400
      milliseconds) interstimulus intervals (ISIs) were measured. RESULTS: Compared
      with control subjects, cortical excitability was higher in migraine only at 250
      milliseconds (P < 0.05; effect size 0.7), while in epilepsy, it was higher at 2,
      5, 250, and 300 milliseconds. Compared with epilepsy, cortical excitability was
      lower in migraine only at 250 milliseconds (P < 0.05; effect size 0.6 compared
      with focal epilepsy and 1.1 compared with idiopathic generalized epilepsy [IGE]).
      CONCLUSIONS: Cortical excitability increases in migraine suggesting the
      involvement of intracortical inhibitory circuits. This may be a common feature
      underlying some of the similarities observed in migraine and epilepsy.

PMID- 22659719
TI  - Association between sleep quality and cognitive impairment among Chinese
      nonagenarians/centenarians.
AB  - PURPOSE: The authors examined the individual association between sleep quality
      and cognitive function among the very elderly. METHODS: The present study
      analyzed data from a survey that was conducted on all residents aged 90 years or
      older in a district; there were 2,311,709 inhabitants in 2005. Cognitive function
      and sleep quality were measured using the 30-item Mini-Mental State Examination
      and the Pittsburgh Sleep Quality Index, respectively. RESULTS: The subjects
      included in the statistical analysis were 216 men and 444 women. Subjects with
      poor sleep quality had significant lower cognitive function scores (P = 0.007)
      and higher prevalence of cognitive impairment (P = 0.035). Subjects with
      cognitive impairment had longer sleep latency (P < 0.0001) and lower sleep
      efficiency percentage (P = 0.006) and more likely reported with poor quality (P =
      0.035). Multiple logistic regressions showed that poor sleep quality was a risk
      factor for cognitive impairment (unadjusted odds ratio, 1.719; 95% confidence
      interval, 1.138-2.597; adjusted odds ratio, 1.759; 95% confidence interval, 1.012
      3.057). CONCLUSIONS: Among longevity Chinese, there is an association between
      sleep quality and cognitive function, and cognitive impairment is associated with
      poor quality, longer sleep latency, and lower sleep efficiency percentage.

PMID- 22659720
TI  - Compound motor action potential interexaminer variability in photoguided
      placement of the recording electrodes.
AB  - Interpretation of neurographic data in follow-up studies of patients with
      neuromuscular disease is sometimes challenging because of the expected
      variability in repeated tests. In this study, we explored whether the
      interexaminer variability of the compound motor action potential (CMAP) amplitude
      is reduced if the examiner is guided by the previously taken photographs of the
      position of the recording electrodes. The CMAPs were recorded from 20 subjects by
      unilateral distal stimulation of the median, ulnar, peroneal, and tibial nerve by
      4 different technicians. All the subjects were examined on 2 occasions (~1 week
      apart). On the first occasion, the technicians recorded the CMAP values according
      to routine protocols. On the second occasion, the technicians had additional
      guidance from photographs displaying the recording electrode positions from the
      first study. The CMAP coefficient of variation (CoV) was calculated for each
      nerve examined by the four technicians. Differences in CoV between the two types
      of tests (i.e., with or without photographs) were evaluated. When the examiners
      were guided by the photographs during electrode application, the CMAP CoV for the
      tibial innervated abductor hallucis (AH) muscle was reduced (P = 0.02) from 18.5%
      to 13%. There were, however, no significant reductions in CoV for the abductor
      pollicis brevis (APB, P = 0.23, median nerve), abductor digiti minimi (P = 0.37,
      ulnar nerve), or extensor digitorum brevis (EDB, P = 0.15, peroneal nerve)
      muscles. Photographic documentation of the CMAP recording electrodes seems to
      have a limited overall effect on interexaminer variability in a subsequent study.

PMID- 22659721
TI  - Usefulness of distal motor latency measurement after palmar stimulation in
      advanced carpal tunnel syndrome.
AB  - The measurement of distal motor latency (DML) after palmar stimulation distal to
      the carpal tunnel (Palmar-DML) was investigated before carpal tunnel release
      (CTR) in 48 advanced carpal tunnel syndrome (CTS) with thenar atrophy and absence
      of motor and sensory responses after wrist stimulation. This allowed measurement
      of the direct effects of stimulation, in assessing the pathologic condition of
      the median nerve. Palmar-DML was measurable in 47 of 48 hands preoperatively,
      which responded to CTR with improvement of thenar atrophy at 1 year
      postoperatively. Also, electrophysiologic recovery presenting reappearance of DML
      after wrist stimulation was shown in 43 hands of those 47 hands. Furthermore,
      sensory nerve conduction velocity was measurable in 24 hands. In contrast, in one
      hand with the absence of Palmar-DML, CTR neither relieved thenar atrophy nor
      induced measurable Palmar-DML. This study demonstrated that Palmar-DML was
      measurable in most advanced CTS, which suggested the major abnormality was focal
      demyelination. This was confirmed by electrophysiologic and clinical improvement
      obtained after CTR. Palmar-DML measurement was useful to elucidate the median
      nerve condition in advanced CTS.

PMID- 22659722
TI  - The second lumbrical-interosseous latency comparison in carpal tunnel syndrome.
AB  - Carpal tunnel syndrome (CTS) is the most common nerve entrapment syndrome.
      Electromyogram (EMG) is beneficial in supporting the diagnosis of CTS. We
      compared standard nerve conduction studies of EMG with median and ulnar motor
      nerve conduction studies from recordings of second lumbrical and interosseal
      muscles in supporting the diagnosis of CTS. In this study, a total of 242
      patients were included, and a total of 375 hands were involved.
      Electrophysiologic CTSs were diagnosed in 283 hands of 161 patients. A
      significant association between second lumbrical-interosseal distal motor latency
      difference (2LI-MDLD) and CTS was found in this study. Statistically, every 0.1
      increment in the 2LI-MDLD value was observed to increase the risk of disease by
      1.74. When a cut-off of >= 0.5 for 2LI-MDLD is taken for predicting CTS, the
      sensitivity of the test is found to be 89.4% and specificity 84.4%. When the cut
      off value for motor distal latency of second lumbrical of the median nerve (2L
      MDL) was taken as >= 3.15 milliseconds in the diagnosis of CTS, the sensitivity
      of the test was 87.3%, and specificity 70.7%. Previous reports and our findings
      suggest that in CTS diagnosis, not only 2LI-MDLD value but also 2L-MDL value are
      easy and rapidly obtainable and offer additional information in very severe cases
      where compound muscle action potentials (CMAP) cannot be recorded from the
      abductor pollicis brevis (APB) muscle.

PMID- 22659723
TI  - Effects of topiramate on peripheral nerve excitability.
AB  - PURPOSE: Antiepileptic drugs are generally used to control the cortical
      hyperexcitable states. But some of them are also effective on the peripheral
      nervous system, so they may be used in some states like neuropathic pain. Several
      recent reports suggest the possible effects of antiepileptic drugs on peripheral
      nerve excitability. Strength duration time properties gives an indirect idea
      about the persistent, paranodal sodium (Na) channels and may indirectly reflect
      the peripheral nerve excitability. Topiramate suppresses the cortical
      hyperexcitability, but previous studies could not prove a significant effect of
      topiramate on peripheral nerves. The aim of this study is to investigate the
      probable nerve excitability changes caused by topiramate. METHODS: Forty migraine
      patients and 40 controls were included in the study. Median motor and sensory
      conduction parameters were recorded. Strength duration properties were also
      recorded from abductor pollicis longus muscle, with the stimulation of median
      nerve. The electrophysiological studies were repeated 4 weeks after the
      initiation of topiramate in the treatment group. RESULTS: Nerve conduction
      parameters were not significantly affected by 4-week topiramate treatment. But
      the strength duration time constant decreased significantly, reflecting a
      reduction in the excitability. This decrement seemed to be more obvious in those
      in whom topiramate was also clinically useful. CONCLUSIONS: The method used
      demonstrated a probable effect of topiramate on the peripheral nerve
      excitability.

PMID- 22659724
TI  - Function of group IB inhibition during assisted stepping in human spinal cord
      injury.
AB  - The aim of this study was to investigate the function of group Ib inhibition
      exerted between ankle synergists during assisted stepping in people with chronic
      motor incomplete spinal cord injury (SCI). During stepping, the soleus (SOL) H
      reflex was conditioned by percutaneous stimulation of the medialis gastrocnemius
      (MG) nerve by a bipolar electrode placed distal and medial to the cathode
      electrode for the tibial nerve. Stimulation was delivered at 0.95 times MG M-wave
      motor threshold with a pulse train at short conditioning-test intervals. To
      counteract movement of recording and stimulating electrodes, a supramaximal
      stimulus at 80 to 100 milliseconds after the test H-reflex was delivered. Stimuli
      were randomly dispersed across the step cycle, which was divided into 16 equal
      bins. The conditioned SOL H-reflex was significantly facilitated throughout the
      stance phase, while it was depressed during the swing phase when compared with
      the unconditioned SOL H-reflex. Ankle clonus during the stance phase may have
      affected the excitability state of spinal motoneuronal and interneuronal
      circuits, but the presence of group Ib inhibition in the swing phase suggests
      that in the absence of loading this spinal circuit is modulated in a physiologic
      manner in human incomplete SCI. Repetitive body loading and unloading promotes
      functional integration of sensory signals mediating load in human SCI.

PMID- 22659725
TI  - Topology-based nonlocal fuzzy segmentation of brain MR image with inhomogeneous
      and partial volume intensity.
AB  - PURPOSE: The aim was to automatically segment brain magnetic resonance (MR) image
      with inhomogeneous and partial volume (PV) intensity for brain and
      neurophysiology analysis. METHODS: Rather than assuming the presence of a single
      bias field over the image data, we first apply a local model to MR image
      analysis. With the brain topology knowledge, several specific local regions are
      selected, and typical brain tissues are then extracted for the prior estimation
      of fuzzy clustering center and member function. A new nonlocal fuzzy labeling
      scheme is applied to global optimization segmentation based on the block
      comparison and distance weight, which is robust to noise and inhomogeneous
      intensity. The nonlocal labeling provides optimized fuzzy member value and local
      intensity estimation of brain tissues such as cerebrospinal fluid (CSF), white
      matter (WM), and gray matter (GM). In addition to inhomogeneous intensity, PV may
      lead to error segmentation. To correct error segmentation because of PV, this
      article also provides two correction schemes. The first one is to extract CSF in
      deep sulci, which captures more CSF candidate by intensity comparison and
      topology shape comparison. The local pure CSF, WM, and GM is then estimated to
      correct the interfaces of CSF/GM and WM/GM. RESULTS: The segmentation experiments
      are performed on both brainweb-simulated images and Internet brain segmentation
      repository database (IBSR) real images. The experimental results demonstrate the
      robust and efficient performance of our approach. CONCLUSIONS: Our approach can
      be applied to automatic segmentation of the brain MR image.

PMID- 22659726
TI  - Epileptiform discharges in acute subdural hematoma:  to treat or not to treat.

PMID- 22659728
TI  - Sorption of atrazine and ametryn by carbonatic and non-carbonatic soils of varied
      origin.
AB  - Sorption of two s-triazines, atrazine and ametryn, by carbonatic soils,
      Histosols, Spodosols and Oxisols was examined. Linear isotherms were observed and
      sorption coefficients (K(d)) of both compounds were significantly lower (alpha =
      0.05) onto carbonatic soils compared to non-carbonatic soils. Furthermore, among
      carbonatic soil types, the marl-carbonatic soils had the lowest sorption
      affinities. K(d) and organic carbon content were highly correlated, suggesting
      predominant influence of organic carbon in the sorption of the s-triazine, except
      in Oxisols and Spodosols where variations suggest other factors. Upon removal of
      organic matter (OM) using sodium hypochlorite and hydrogen peroxide, the K(d)
      values were reduced by ~90%, indicating minimal contribution of mineral surfaces.
      Thus OM compositional differences likely explain the large variation in s
      triazine sorption within and between soil orders. This study highlights the need
      to consider OM composition in addition to quantity when determining pesticide
      applications rates, particularly for carbonatic soils.

PMID- 22659733
TI  - The development and function of follicular helper T cells in immune responses.
AB  - Follicular helper T cells (Tfh) have been referred as a lineage that provides a
      help for B cells to proliferate and undergo antibody affinity maturation in the
      germinal center. Evidence has supported that Tfh subset development, like other
      lineages, is dependent on microenvironment where a particular transcriptional
      program is initiated. It has been shown that Bcl-6 and IL-21 act as master
      regulators for the development and function of Tfh cells. Tfh dysregulation is
      involved in the development of autoimmune pathologies, such as systemic lupus
      erythematosus, rheumatoid arthritis and other autoimmune diseases. The present
      review highlights the recent advances in the field of Tfh cells and focus on
      their development and function.

PMID- 22659735
TI  - Sarcomas as a mise en abyme of mesenchymal stem cells: exploiting
      interrelationships for cell mediated anticancer therapy.
AB  - Mise en abyme meaning "placed into abyss or infinite recurrence" is an apt
      paradigm for the relentless growth of sarcoma cells. Its alternative meaning,
      "self-reflexive embedding" fits the central role attributed to cancer stem cells
      (CSCs). Diversely sourced and defined, mesenchymal stem cells (MSCs) may be the
      cells of sarcoma origin, evolve a CSC phenotype and/or contribute to tumor growth
      through inherent qualities for homing, neovascularization, paracrine cross
      feeding, microvesicle secretion, cell fusion, entosis and immune modulation.
      Exploiting these qualities, MSC expressing modified forms of the TNF-related
      apoptosis-inducing ligand (Apo2L/TRAIL) are being developed to complement more
      conventional radiation and chemotherapy.

PMID- 22659734
TI  - Perspectives on cancer stem cells in osteosarcoma.
AB  - Osteosarcoma is an aggressive pediatric tumor of growing bones that, despite
      surgery and chemotherapy, is prone to relapse. These mesenchymal tumors are
      derived from progenitor cells in the osteoblast lineage that have accumulated
      mutations to escape cell cycle checkpoints leading to excessive proliferation and
      defects in their ability to differentiate appropriately into mature bone-forming
      osteoblasts. Like other malignant tumors, osteosarcoma is often heterogeneous,
      consisting of phenotypically distinct cells with features of different stages of
      differentiation. The cancer stem cell hypothesis posits that tumors are
      maintained by stem cells and it is the incomplete eradication of a refractory
      population of tumor-initiating stem cells that accounts for drug resistance and
      tumor relapse. In this review we present our current knowledge about the biology
      of osteosarcoma stem cells from mouse and human tumors, highlighting new insights
      and unresolved issues in the identification of this elusive population. We focus
      on factors and pathways that are implicated in maintaining such cells, and
      differences from paradigms of epithelial cancers. Targeting of the cancer stem
      cells in osteosarcoma is a promising avenue to explore to develop new therapies
      for this devastating childhood cancer. 

PMID- 22659736
TI  - Berry anthocyanidins synergistically suppress growth and invasive potential of
      human non-small-cell lung cancer cells.
AB  - Berry anthocyanidins (cyanidin, malvidin, peonidin, petunidin and delphinidin)
      have increasingly been explored for their anticancer effects; however, their
      combinatorial effects as a mixture, as present in blueberry, bilberry and Indian
      blackberry ('Jamun') remain untested. In this study, we demonstrate for the first
      time that the combination of suboptimal concentrations of equimolar
      anthocyanidins synergistically inhibited growth of two aggressive non-small-cell
      lung cancer cell lines, with minimal effects on non-tumorigenic cell viability.
      The induction of cell-cycle arrest, apoptosis and suppression of NSCLC cell
      invasion and migration were also significantly greater with the mixture than
      individual anthocyanidins. The superior effects of the combinatorial treatment
      presumably resulted from its effects on the oncogenic Notch and WNT pathways and
      their downstream targets (beta-catenin, c-myc, cyclin D1, cyclin B1, pERK, MMP9
      and VEGF proteins), enhanced cleavage of the apoptotic mediators Bcl2 and PARP
      and enhanced inhibition of TNFalpha-induced NF-kappa B activation. In vivo, both
      the native mixture of anthocyanidins from bilberry (0.5mg/mouse) and the most
      potent anthocyanidin, delphinidin (1.5mg/mouse) significantly inhibited the
      growth of H1299 xenografts in nude miceby ~60%. Notably, the effective dose of
      delphinidin in the anthocyanidin mixture was 8-fold lower than delphinidin alone,
      further emphasizing synergism. Our results thus demonstrate therapeutic potential
      of berries rich in this mixture of diverse anthocyanidins for non-small-cell lung
      cancer treatment and to prevent its future recurrence and metastasis.

PMID- 22659737
TI  - p53 Mutation suppresses adult neurogenesis in medaka fish (Oryzias latipes).
AB  - Tumor suppressor p53 negatively regulates self-renewal of neural stem cells in
      the adult murine brain. Here, we report that the p53 null mutation in medaka fish
      (Oryzias latipes) suppressed neurogenesis in the telencephalon, independent of
      cell death. By using 5-bromo-29-deoxyuridine (BrdU) immunohistochemistry, we
      identified 18 proliferation zones in the brains of young medaka fish; in situ
      hybridization showed that p53 was expressed selectively in at least 12
      proliferation zones. We also compared the number of BrdU-positive cells present
      in the whole telencephalon of wild-type (WT) and p53 mutant fish. Immediately
      after BrdU exposure, the number of BrdU-positive cells did not differ
      significantly between them. One week after BrdU-exposure, the BrdU-positive cells
      migrated from the proliferation zone, which was accompanied by an increased
      number in the WT brain. In contrast, no significant increase was observed in the
      p53 mutant brain. Terminal deoxynucleotidyl transferase (dUTP) nick end-labeling
      revealed that there was no significant difference in the number of apoptotic
      cells in the telencephalon of p53 mutant and WT medaka, suggesting that the
      decreased number of BrdU-positive cells in the mutant may be due to the
      suppression of proliferation rather than the enhancement of neural cell death.
      These results suggest that p53 positively regulates neurogenesis via cell
      proliferation.

PMID- 22659738
TI  - AMP-activated protein kinase (AMPK) activation is involved in chrysin-induced
      growth inhibition and apoptosis in cultured A549 lung cancer cells.
AB  - Here we show that chrysin induces growth inhibition and apoptosis in cultured
      lung cancer A549 cells, and activation of AMP-activated protein kinase (AMPK) may
      contribute to this process. Our Western-blots results demonstrated a significant
      AMPK activation after chrysin treatment in A549 cells. Inhibition of AMPK by
      shRNA-mediated gene silencing, or by its inhibitor, diminished chrysin-induced
      A549 cell growth inhibition and apoptosis. Forced activation of AMPK by
      introducing a constitutively active form of AMPKalpha (CA-AMPKalpha), or by its
      activators, mimicked chrysin's effect. For mechanism analysis, we found chrysin
      inhibited Akt/mammalian target of rapamycin (mTOR) activation, and knocking-down
      of AMPK by shRNA almost reversed this effect. Finally, we observed that a
      relative low dose of chrysin enhanced doxorubicin-induced AMPK activation to
      promote A549 cell apoptosis. Our study suggests that activation of AMPK by
      chrysin contributes to Akt suppression, growth inhibition and apoptosis in human
      lung cancer cells, and agents that could activate AMPK may serve as useful
      adjuvants for traditional chemotherapy against lung cancer.

PMID- 22659739
TI  - Size-controlled nanopores in lipid membranes with stabilizing electric fields.
AB  - Molecular dynamics (MD) has been shown to be a useful tool for unveiling many
      aspects of pore formation in lipid membranes under the influence of an applied
      electric field. However, the study of the structure and transport properties of
      electropores by means of MD has been hampered by difficulties in the maintenance
      of a stable electropore in the typically small simulated membrane patches. We
      describe a new simulation scheme in which an initially larger porating field is
      systematically reduced after pore formation to lower stabilizing values to
      produce stable, size-controlled electropores, which can then be characterized at
      the molecular level. A new method allows the three-dimensional modeling of the
      irregular shape of the pores obtained as well as the quantification of its
      volume. The size of the pore is a function of the value of the stabilizing field.
      At lower fields the pore disappears and the membrane recovers its normal shape,
      although in some cases long-lived, fragmented pores containing unusual lipid
      orientations in the bilayer are observed.

PMID- 22659740
TI  - Comparison of mucosal absorption-enhancing activity between a claudin-3/-4 binder
      and a broadly specific claudin binder.
AB  - Intercellular spaces between adjacent mucosal epithelial cells are sealed by
      tight junctions (TJs) that prevent the free movement of solutes across the
      epithelium. Claudins (CLs), a family of 27 integral membrane proteins, are
      essential components for TJ seals. We previously used a CL-3/-4 binder, the C
      terminal fragment of Clostridium perfringens enterotoxin (C-CPE), to show that CL
      modulation is a promising method to enhance mucosal absorption. Recently, by
      using a C-CPE mutant library, we developed a CL binder (m19) with broad
      specificity to CL-1, -2, -4, and -5. Here, we compared the mucosal absorption
      enhancing activity of C-CPE and m19. Both CL binders enhanced jejunal absorption
      of dextran with a molecular mass of 4000 and 150,000 Da and nasal absorption of
      dextran with a mass of 4000 Da but not 150,000 Da in rats. Although both binders
      showed similar nasal absorption-enhancing activity of dextran (4000 Da), m19
      exhibited a more potent jejunal absorption-enhancing effect than that of C-CPE.
      These findings suggest that mucosal absorption-enhancing activity may be modified
      by modulating CL specificity.

PMID- 22659741
TI  - Impaired antigen presentation and potent phagocytic activity identifying tumor
      tolerant human monocytes.
AB  - Monocyte exposure to tumor cells induces a transient state in which these cells
      are refractory to further exposure to cancer. This phenomenon, termed "tumor
      tolerance", is characterized by a decreased production of proinflammatory
      cytokines in response to tumors. In the past, we found that this effect comprises
      IRAK-M up regulation and TLR4 and CD44 activation. Herein we have established a
      human model of tumor tolerance and have observed a marked down-regulation of
      MHCII molecules as well as the MHCII master regulator, CIITA, in
      monocytes/macrophages. These cells combine an impaired capability for antigen
      presentation with potent phagocytic activity and exhibit an M2-like phenotype. In
      addition circulating monocytes isolated from Chronic Lymphocytic Leukemia
      patients exhibited the same profile as tumor tolerant cells after tumor ex vivo
      exposition.

PMID- 22659742
TI  - MgATP-concentration dependence of protection of yeast vacuolar V-ATPase from
      inactivation by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole supports a bi-site
      catalytic mechanism of ATP hydrolysis.
AB  - Catalytic site occupancy of the yeast vacuolar V-ATPase during ATP hydrolysis in
      the presence of an ATP-regenerating system was probed using sensitivity of the
      enzyme to inhibition by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl). The
      results show that, regardless of the presence or absence of the proton-motive
      force across the vacuolar membrane, saturation of V-ATPase activity at increasing
      MgATP concentrations is accompanied by only partial protection of the enzyme from
      inhibition by NBD-Cl. Both in the presence and absence of an uncoupler, complete
      protection of V-ATPase from inhibition by NBD-Cl requires MgATP concentrations
      that are significantly higher than those expected from the K(m) values for MgATP.
      The results are inconsistent with a tri-site model and support a bi-site model
      for a mechanism of ATP hydrolysis by V-ATPase.

PMID- 22659743
TI  - Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast
      differentiation.
AB  - We previously demonstrated that sphingosine 1-phosphate (S1P) receptor-mediated
      signaling induced proliferation and prostaglandin productions by synovial cells
      from rheumatoid arthritis (RA) patients. In the present study we investigated the
      role of S1P receptor-mediated signaling for osteoblast differentiation. We
      investigated osteoblast differentiation using C2C12 myoblasts, a cell line
      derived from murine satellite cells. Osteoblast differentiation was induced by
      the treatment of bone morphogenic protein (BMP)-2 in the presence or absence of
      either S1P or FTY720 (FTY), a high-affinity agonist of S1P receptors. Osteoblast
      differentiation was determined by osteoblast-specific transcription factor, Runx2
      mRNA expression, alkaline phosphatase (ALP) activity and osteocalcin production
      by the cells. Smad1/5/8 and extracellular signal-regulated kinase (ERK) 1/2
      phosphorylation was examined by Western blotting. Osteocalcin production by C2C12
      cells were determined by ELISA. Runx2 expression and ALP activity by BMP-2
      stimulated C2C12 cells were enhanced by addition of either S1P or FTY. Both S1P
      and FTY enhanced BMP-2-induced ERK1/2 and Smad1/5/8 phosphorylation. The effect
      of FTY was stronger than that of S1P. S1P receptor-mediated signaling on
      osteoblast differentiation was inhibited by addition of mitogen-activated protein
      kinase/ERK kinase (MEK) 1/2 inhibitor, indicating that the S1P receptor-mediated
      MEK1/2-ERK1/2 signaling pathway enhanced BMP-2-Smad signaling. These results
      indicate that S1P receptor-mediated signaling plays a crucial role for osteoblast
      differentiation.

PMID- 22659745
TI  - Hyaluronan-chondroitin hybrid oligosaccharides as new life science research
      tools.
AB  - Hyaluronan and chondroitin are glycosaminoglycans well-known as components of
      pharmaceutical agents and health foods. From these attractive molecules, using
      transglycosylation reaction of testicular hyaluronidase, we synthesized hybrid
      neo-oligosaccharides not found in nature. We also found a new site between the
      chondroitin disaccharide unit and hyaluronan disaccharide unit recognized by a
      hyaluronan lyase specific to hyaluronan using these hybrid oligosaccharides as
      substrates. We hope that these hybrid oligosaccharides will help to elucidate the
      involvement of hyaluronan, chondroitin, and chondroitin sulfates in the
      mechanisms of cell functions and diseases, based on the structures of these
      glycosaminoglycans.

PMID- 22659744
TI  - DNA damage down-regulates DeltaNp63alpha and induces apoptosis independent of
      wild type p53.
AB  - The tumor suppressor p53 is pivotal in cell growth arrest and apoptosis upon
      cellular stresses including DNA damage. Mounting evidence indicates that p63
      proteins, which are homologs of p53, are also involved in apoptosis under certain
      circumstances. In this study, we found that treatment with DNA damage agents
      leads to down-regulation of DeltaNp63alpha and induces apoptosis in FaDu and
      HaCat cells carrying mutant p53. Further study shows that DNA damage reduces
      steady-state mRNA level of DeltaNp63alpha, but has little effect on its protein
      stability. In addition, knockdown of endogenous DeltaNp63alpha directly induces
      apoptosis and sensitizes cells to DNA damage, while exogenous expression of
      DeltaNp63alpha partially confers cellular resistance to DNA damage. Together,
      these data suggest that DNA damage down-regulates DeltaNp63alpha, which may
      directly contribute to DNA damage-induced apoptosis.

PMID- 22659754
TI  - Direct deposition of two nanomaterials with the same surface charge using a
      liquid-liquid interface.
AB  - Two negatively charged nanoparticles (SDS-coated SWCNT and polydiacetylene
      nanocrystals) were sequentially adsorbed onto the same water-hexane interface.
      The absorbed film can be transferred onto a solid substrate. Repeating the
      adsorption and transfer process enables assembly of the two nanoparticles in a
      layer-by-layer growth fashion up to three bi-layers.

PMID- 22659746
TI  - Endotoxin-induced basal respiration alterations of renal HK-2 cells: a sign of
      pathologic metabolism down-regulation.
AB  - To study the mechanism of oxygen regulation in inflammation-induced acute kidney
      injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide,
      LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by
      high-resolution respirometry and electron spin resonance spectroscopy. These two
      complementary methods have shown that HK-2 cells exhibit a decreased oxygen
      consumption rate when treated with LPS. Surprisingly, this cellular respiration
      alteration persists even after the stress factor was removed. We suggested that
      this irreversible decrease in renal oxygen consumption after LPS challenge is
      related to a pathologic metabolic down-regulation such as a lack of oxygen
      utilization by cells.

PMID- 22659755
TI  - Ion-pair triple helicates and mesocates self-assembled from ditopic 2,2'
      bipyridine-bis(urea) ligands and Ni(II) or Fe(II) sulfate salts.
AB  - NiSO(4) and FeSO(4) self-assemble with heteroditopic ligands (L) comprising 2,2'
      bipyridine and o-phenylene-(bis)urea cation- and anion-binding sites,
      respectively, into [ML(3)SO(4)] (M = Ni(2+), Fe(2+)) triple-stranded ion-pair
      helicates and mesocates.

PMID- 22659759
TI  - Topical ketamine cream in the treatment of painful diabetic neuropathy: a
      randomized, placebo-controlled, double-blind initial study.
AB  - BACKGROUND: Painful diabetic neuropathy remains a difficult pathologic condition
      to manage effectively despite numerous pharmacologic interventions. A randomized,
      placebo-controlled, double-blind study was undertaken to determine whether
      topical 5% ketamine cream is effective in reducing the pain of diabetic
      neuropathy. METHODS: Seventeen diabetic patients completed the study. The
      Michigan Neuropathy Screening Instrument was used to determine whether the
      neuropathy was likely caused by the diabetic condition. Hemoglobin A(1c) levels
      were measured before treatment. Patients applied 1 mL of either ketamine cream or
      placebo cream for 1 month. The intensity of seven different pain characteristics
      was evaluated before and after treatment. A two-way repeated analysis of variance
      design was used to test for differences between treatments and within patients
      (time). RESULTS: We found no significant treatment main effect, but pain improved
      significantly over time in both groups. There was no statistical interaction
      effect (treatment * time) in any of the pain characteristics, indicating that
      pain improved in the two treatment groups similarly with time. CONCLUSIONS: The
      5% topical ketamine cream was no more effective than was placebo in relieving
      pain caused by diabetic neuropathy.

PMID- 22659760
TI  - Ultrasonography and magnetic resonance imaging in the diagnosis of Morton's
      neuroma.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) and ultrasonography are used widely
      for the diagnosis of Morton's neuroma. The aim of this study was to assess the
      accuracy of these two modalities as diagnostic tools in Morton's neuroma.
      METHODS: Fifty feet of 47 consecutive patients (39 women and 8 men; mean age, 46
      years; age range, 36-64 years) who presented between January 1, 2005, and June
      30, 2008, were included in the study. Twenty-five feet were investigated with
      ultrasonography and 25 with MRI. Morton's neuroma was confirmed surgically and
      histologically in all of the patients. A Student unpaired t test was applied.
      RESULTS: Twenty-two MRIs were diagnostic (sensitivity, 88%). Three patients with
      negative MRI findings underwent ultrasonography and were found to have a neuroma
      smaller than 5 mm. Twenty-four ultrasound scans demonstrated the neuroma
      (sensitivity, 96%), with five neuromas being smaller than 5 mm. CONCLUSIONS:
      Ultrasonography has a slightly higher sensitivity in the diagnosis of Morton's
      neuroma, particularly of neuromas smaller than 5 mm, and should be the preferred
      imaging modality in suspected cases, and MRI should be reserved for cases with
      equivocal diagnosis.

PMID- 22659761
TI  - Foot-to-shoe mismatch and rates of referral in Special Olympics athletes.
AB  - BACKGROUND: Improperly fitted shoes are frequently seen in athletes participating
      in Special Olympics competitions. This foot-to-shoe mismatch may result in
      deformities as well as discomfort and reduced performance or injuries in
      competitions. A primary purpose for providing medical screenings is to identify
      conditions unknown and to promptly refer to an appropriate provider for
      evaluation and care. This study attempts to determine the prevalence of
      improperly fitted shoes and the rate of referral for Special Olympics athletes
      screened at Fit Feet venues. METHODS: To evaluate the foot-to-shoe mismatch and
      rate of referral, 4,094 Fit Feet screenings of Special Olympics athletes
      participating in US competitions in 2005 to 2009 were analyzed. The participants
      were 58.5% male and 41.5% female, with a median age of 25.6 years. A power
      analysis and the chi(2) test were used. The athletes voluntarily underwent a foot
      screening that followed the standardized Special Olympics Fit Feet protocol. The
      Brannock Device for measuring feet was used to assess proper fit. RESULTS: A
      proper fit was found in 58.56% of the athletes, with 28.60% wearing shoes too big
      and 12.84% wearing shoes too small. Unrelated to shoe fit, 20% of the athletes
      required referrals for professional follow-up based on abnormal clinical
      findings. CONCLUSIONS: There is a significant (41.44%) mismatch of foot to shoe
      in Special Olympics athletes. The most common mismatch is a shoe too big, with a
      much smaller number of athletes having shoes too small. Awareness of this foot-to
      shoe incompatibility may be useful for the development of shoes better designed
      for athletes with a foot structure not consistent with conventional shoes.
      Because 20% of the athletes required a referral for professional follow-up, Fit
      Feet examinations are important for identifying athletes with conditions that can
      be more readily evaluated and treated, thus improving the athletes' comfort and
      performance. Beyond knowing the rate of referral, future studies can determine
      the conditions or findings that necessitate a referral and the ultimate outcome
      of that referral.

PMID- 22659762
TI  - Matrixplasty for the treatment of severe incurved toenail with growth plate
      deformity.
AB  - BACKGROUND: Severely incurved toenails are accompanied by deformity of the
      toenail growth plate. In such a condition, partial removal of the nail and nail
      bed and simple unfolding of the nail itself frequently result in the recurrence
      of symptoms. We sought to design and develop a new technique for the treatment of
      incurved toenail with growth plate deformity and to report the results of
      treating this disease entity. METHODS: Forty consecutive patients (52 cases)
      underwent treatment of symptomatic incurved toenails with a new technique named
      matrixplasty. The mean +/- SD patient age was 40.3 +/- 18.9 years. Last follow-up
      was at a mean +/- SD of 18.0 +/- 1.3 months. An American Orthopedic Foot and
      Ankle Society (AOFAS) forefoot hallux score was assigned, and patients were
      evaluated before treatment and at last follow-up. Patient satisfaction and the
      recurrence rate of the deformity were evaluated. For evaluation of improvement in
      toenail shape, the center to edge angle of the toenail was measured before
      treatment and at last follow-up. The complication rate was also evaluated.
      RESULTS: All of the ingrown toenails healed, and the nail deformities were
      corrected within 3 weeks after the procedure. None of the incurved toenails had
      recurred by last follow-up. The mean pretreatment AOFAS forefoot hallux score was
      72.9, and it improved to 99.6 by last follow-up (P < .001). Every patient was
      very satisfied or satisfied with the results of treatment. The mean +/- SD center
      to edge angle of the toenail improved from 53.3 degrees  +/- 9.5 degrees  to 15.3
      degrees  +/- 5.2 degrees  by last follow-up (P < .001). Minor paronychia, which
      was managed with local wound dressing and oral antibiotics, was identified in
      four cases. No other complication was identified. CONCLUSIONS: Matrixplasty
      showed excellent clinical results in the treatment of severe incurved toenail,
      and this newly developed procedure showed improvement of the deformed toenail and
      its growth plate.

PMID- 22659763
TI  - Dynamic midfoot kinematics in subjects with medial tibial stress syndrome.
AB  - BACKGROUND: Medial tibial stress syndrome (MTSS) is a common diagnosis. Several
      studies have demonstrated that excessive static navicular drop (ND) is related to
      the diagnosis. However, no studies have yet investigated ND and the velocity of
      ND during dynamic conditions. The aim of this study was to evaluate ND
      characteristics in patients with MTSS in dynamic and static conditions. METHODS:
      In a case-control study, 14 patients diagnosed as having MTSS were included from
      an orthopedic outpatient clinic. A control group consisting of 14 healthy
      participants was matched regarding age, sex, and typical sporting activity.
      Navicular drop was evaluated during treadmill walking by a two-dimensional video
      analysis. Static foot posture, static ND, dynamic ND (dND), and velocity of dND
      were compared. RESULTS: The two groups were comparable in relation to age, sex,
      height, weight, and foot size. No significant difference was found in static foot
      posture. Static ND showed a mean difference of 1.7 mm between the groups (P =
      .08). During treadmill walking, patients with MTSS had, on average, a 1.5-mm
      larger dND (P =.004) and a 2.4-mm/sec-larger mean velocity of dND (P = .03).
      CONCLUSIONS: Patients with MTSS display a larger ND and a higher ND velocity
      during treadmill walking. Increased ND velocity may be important to this
      condition. Future studies should include velocity of dND to investigate the
      mechanisms of dND in relation to overuse injuries.

PMID- 22659764
TI  - Peripheral and central bone mineral density in Charcot's neuroarthropathy
      compared in diabetic and nondiabetic populations.
AB  - BACKGROUND: This prospective study was performed to compare calcaneal and lumbar
      bone mineral density (BMD) in individuals with and without diabetes mellitus. We
      compared bone density with the time from onset of Charcot's neuroarthropathy (CN)
      in patients with unilateral, nonoperative, reconstructive-stage CN. The final
      purpose was to investigate the role that sex, age, and serum vitamin D level may
      have in osseous recovery. METHODS: Thirty-three individuals were divided into
      three groups: controls and patients with diabetes mellitus with and without CN.
      Peripheral instantaneous x-ray imaging and dual-energy x-ray absorptiometry were
      performed. RESULTS: The calcaneal BMD of patients with diabetes mellitus and CN
      was lower than that of the control group (P < .01) but was not significantly
      lower than that of patients with diabetes mellitus alone. There was no
      statistically significant difference in lumbar T-scores between groups. Women
      demonstrated lower BMD than did men (P = .02), but patients 60 years and older
      did not demonstrate significantly lower BMD than did patients younger than 60
      years (P = .135). A negative linear relationship was demonstrated between time
      and BMD in patients with CN. CONCLUSIONS: The results of this study suggest that
      lumbar BMD does not reflect peripheral BMD in patients with diabetes mellitus and
      reconstructive-stage CN. This study has clinical implications when reconstructive
      osseous surgery is planned in patients with CN.

PMID- 22659765
TI  - Topical application of a gentamicin-collagen sponge combined with systemic
      antibiotic therapy for the treatment of diabetic foot infections of moderate
      severity: a randomized, controlled, multicenter clinical trial.
AB  - BACKGROUND: The aim of this pilot study was to determine the safety and potential
      benefit of adding a topical gentamicin-collagen sponge to standard of care
      (systemic antibiotic therapy plus standard diabetic wound management) for
      treating diabetic foot infections of moderate severity. METHODS: We randomized 56
      patients with moderately infected diabetic foot ulcers in a 2:1 ratio to receive
      standard of care plus the gentamicin-collagen sponge (treatment group, n = 38) or
      standard of care only (control group, n = 18) for up to 28 days of treatment.
      Investigators performed clinical, microbiological, and safety assessments at
      regularly scheduled intervals and collected pharmacokinetic samples from patients
      treated with the gentamicin-collagen sponge. Test of cure was clinically assessed
      14 days after all antibiotic therapy was stopped. RESULTS: On treatment day 7, we
      noted clinical cure in no treatment patients and three control patients (P =
      .017). However, for evaluable patients at the test-of-cure visit, the treatment
      group had a significantly higher proportion of patients with clinical cure than
      did the control group (22 of 22 [100.0%] versus 7 of 10 [70.0%]; P =.024).
      Patients in the treatment group also had a higher rate of eradication of baseline
      pathogens at all visits (P <= .038) and a reduced time to pathogen eradication (P
      < .001). Safety data were similar for both groups. CONCLUSIONS: Topical
      application of the gentamicin-collagen sponge seems safe and may improve clinical
      and microbiological outcomes of diabetic foot infections of moderate severity
      when combined with standard of care. These pilot data suggest that a larger trial
      of this treatment is warranted.

PMID- 22659766
TI  - Acellular fetal bovine dermal matrix in the treatment of nonhealing wounds in
      patients with complex comorbidities.
AB  - BACKGROUND: In contrast to the narrow indications for living skin equivalents,
      extracellular matrix biomaterials are clinically used in a wide range of wound
      healing applications. Given the breadth of possible uses, the goal of this study
      was to retrospectively compile and analyze the clinical application and
      effectiveness of an extracellular matrix biomaterial derived from fetal bovine
      dermis (PriMatrix; TEI Biosciences, Boston, Massachusetts) in patients treated by
      a single physician and monitored postsurgically in an outpatient wound care
      center. METHODS: A retrospective medical record review was conducted of
      consecutive patients treated from January 2007 through January 2009 with meshed
      PriMatrix after sharp/surgical debridement and coverage with standard moist wound
      therapy dressings. RESULTS: Twenty-nine patients and 34 wounds were compiled. All
      of the wounds were unresponsive to conservative treatment owing to complications,
      including infection, exposed bone or tendon, and other comorbidities known to
      delay healing. Wounds included 11 diabetic ulcers, 8 venous stasis ulcers, 10
      nonhealing traumatic wounds, and 5 other chronic wounds. Thirty of 34 wounds
      healed, with four patients lost to follow-up. Mean time to healing for diabetic
      foot ulcers was 105 days with an average of 2.6 PriMatrix applications. Mean time
      to healing for venous, traumatic, and other chronic wounds was 74 to 82 days with
      an average of 1.2 to 1.4 PriMatrix applications. CONCLUSIONS: In patients with
      comorbidities known to delay healing, the implantation of PriMatrix promoted the
      healing and, ultimately, full reepithelialization of otherwise unresponsive
      wounds of varied etiology, including those with complications of infection or
      exposed bone or tendon.

PMID- 22659767
TI  - Relation between popliteal-tibial artery atherosclerosis and global glycolytic
      metabolism in the affected diabetic foot: a pilot study using quantitative FDG
      PET.
AB  - BACKGROUND: We evaluated the extent and the degree of active atherosclerosis in
      the popliteal-tibial arteries by quantitative techniques using [(18)F]-2-fluoro-2
      deoxy-d-glucose-positron emission tomography (FDG-PET). An effort was made to
      determine whether there was a positive correlation between the level of ongoing
      atherosclerosis and subsequent chronic ischemia in the diabetic foot. METHODS: A
      total of 115 diabetic patients were enrolled in this prospective research study
      and underwent lower-extremity FDG-PET and magnetic resonance imaging. We selected
      36 diabetic patients with complicated diabetic foot for this analysis (11 men, 25
      women; mean age, 59.5 years; age range, 36-85 years). Ten nondiabetic control
      participants (6 men, 4 women; mean age, 59.7 years; age range, 27-88 years) were
      also included for comparison. Only patients with blood glucose levels less than
      200 mg/100 mL were enrolled in this study. The metabolic volumetric product
      (MVP), for each patient was calculated multiplying foot average maximum standard
      uptake value (SUV(max)) by foot volume. Pearson correlation analysis between foot
      mean SUV(max) alone and the degree of atherosclerosis and between the foot MVP
      and the degree of atherosclerosis was performed as measured by FDG-PET. A t test
      was used to assess for significant differences in foot SUV(max) and foot MVP
      among varying degrees of atherosclerosis, using P < .05 as the criterion for
      statistical significance. RESULTS: Foot SUV(max) significantly correlated (P <
      .05) with the ratio of popliteal-tibial artery SUV(max) to background SUV
      (Pearson correlation coefficient = 0.49). Foot MVP was also significantly
      correlated (P < .05) with the ratio of popliteal-tibial artery SUV(max) to
      background SUV (Pearson correlation coefficient = 0.69). CONCLUSIONS: Using FDG
      PET, one may be able to detect and quantify the degree of increased metabolic
      activity of early active atherosclerosis and the associated chronic tissue
      ischemic effects at the regional level and globally throughout the whole body
      during the asymptomatic phase of disease.

PMID- 22659768
TI  - Malignant eccrine acrospiroma: a case report.
AB  - The authors present a case of seemingly textbook digital osteomyelitis with
      draining ulceration. Per protocol, specimens were sent to pathology with the
      intent to verify and identify the offending organisms. Surprisingly, the textbook
      osteomyelitis returned with a pathological diagnosis of rare sweat gland tumor,
      malignant eccrine acropsiroma, prompting immediate systemic medical workup and
      treatment. This case emphasizes the importance of proper laboratory workup of all
      surgically removed specimens, despite having a "typical" presentation.

PMID- 22659769
TI  - Management of nonreducible lesser toe interphalangeal dislocation: an unusual
      injury.
AB  - Interphalangeal joint dislocations of the lesser toes are relatively rare in
      clinical practice. Most nonreducible interphalangeal joint dislocations occur as
      a result of rupture or interposition of the plantar plate or of the collateral
      ligament in the joint space, thus hindering a closed reduction and, in most
      cases, compelling an open reduction. A post-reduction radiologic exploration is
      then essential to identify such an entity and proceed consequently. In some
      cases, such as the one introduced herein, a misdiagnosis, along with an
      inadequate surgical correction may lead to recurrence of the deformity and,
      ultimately, to a salvage arthrodesis.

PMID- 22659770
TI  - Interphalangeal joint involvement of the big toe in gout: a rare presentation.
AB  - Atypical presentation of gout can cause diagnostic dilemmas. We report a case of
      gout that presented with an expansile lytic lesion involving the interphalangeal
      joint of the hallux, lack of a history of gout, and an associated solitary lung
      nodule. Magnetic resonance imaging showed an expansile destructive bony lesion
      with soft-tissue involvement suggestive of a possible bony metastasis. A needle
      biopsy was performed, and histopathologic features were diagnostic of chronic
      tophaceous gout.

PMID- 22659771
TI  - Evaluating the biomechanics of the pediatric foot in Turner syndrome: a case
      report.
AB  - Turner syndrome is a genetic disorder that can present clinically with multiple
      concurrent comorbidities. This case report describes a 12-year-old girl with
      Turner syndrome who was referred for podiatric medical assessment and explores
      the application of optoelectronic stereophotogrammetry in the biomechanical
      assessment of the foot and lower limb. A four-segment kinematic foot model using
      14-mm reflective markers was applied to the foot and lower limb of the patient to
      track motion at the tibia, rearfoot, forefoot, and hallux. Kinematic results
      presented in this case study illustrate evidence of excessive foot pronation
      throughout the stance phase of gait. Whether excessive pronation is a general
      characteristic of foot function in Turner syndrome remains to be confirmed, but
      the findings presented suggest that a comprehensive evaluation of foot
      biomechanics in patients with Turner syndrome may be warranted.

PMID- 22659772
TI  - A case of keratosis lichenoid chronica.
AB  - Keratosis lichenoid chronica is a rare dermatologic anomaly believed to be a
      variant of lichen planus. It presents as violaceous, nodular lesions usually on
      the dorsal aspects of the extremities and the trunk. The disease is refractory to
      treatment although psoralen ultraviolet A therapy and oral retinoids have been
      proven useful in some cases. Here we present the case of a 58-year-old male
      diagnosed with keratosis lichenoid chronica.

PMID- 22659774
TI  - Considerations for disease impact and outcome measures in vulvar disease.
AB  - OBJECTIVE: Reliable and valid outcome measures are essential both in clinical
      practice and in clinical trials to be able to monitor response to treatments. In
      this review, we consider existing outcome measures currently used in clinical
      practice and discuss the need for vulvar specific measures. MATERIALS AND
      METHODS: We have reviewed the existing literature describing outcome measure and
      disease impact scales for dermatologic and vulvar conditions. RESULTS: A
      combination of measures including clinician-determined severity and patient
      related quality-of-life indices are often used to assess different aspects of a
      disease. Health-related quality-of-life measures as scored by the patient are
      being increasingly recognized as the main driver in therapeutic decision making
      and are also important in developing service provision. Numerous disease-specific
      severity scores exist within dermatology, as do quality-of-life indices. However,
      none has been specifically designed to cover all aspects of vulvar disease.
      CONCLUSIONS: It is timely to consider the assessment of vulvar disease both in
      terms of impact on the patient and disease severity as assessed by the clinician
      to design well-constructed clinical trials for the management of vulvar disease.
      Owing to the sensitive nature of the problem, patients' needs and expectations
      are often different from general dermatology patients. We suggest that scales to
      monitor outcomes in the vulvar population should be devised by adapting and
      combining existing scales so they are relevant to our patients' needs.

PMID- 22659773
TI  - Is there a role for cervicography in the detection of premalignant lesions of the
      uterine cervix?: a Brazilian experience.
AB  - OBJECTIVE: This study aimed to compare cervical cancer screening by cervicography
      with screening by Pap test. MATERIALS AND METHODS: This was a comparative
      multicenter study of cervical cytology and cervicography. The cervicography
      (slides of the cervix) was taken after the Pap test was completed. In total,
      samples were collected from 1176 patients. Colposcopy with biopsy was considered
      the gold standard for the final diagnosis of lesions observed by the Pap test and
      cervicography. Statistical analysis was performed using the binomial test.
      RESULTS: In cases in which the Pap test was negative for cervical lesions,
      diagnosis by cervicography was positive in 15 cases of cervical intraepithelial
      neoplasia 1 (CIN 1) (p = .00052), in 1 case of CIN 2, in 1 case of CIN 3, and in
      1 case of cancer. However, cervicography produced 3 false-positive results (p <
      .0001). CONCLUSIONS: Cervicography may be used as a complementary screening
      method to the Pap test for cervical cancer.

PMID- 22659775
TI  - Management of microinvasive cervical cancer: a British Society for Colposcopy and
      Cervical Pathology audit.
AB  - The incidence of microinvasive cervical cancers seems to be increasing as a
      result of screening. However, there is little national or international guidance
      on best management or follow-up of women treated with conservation of the cervix.
      OBJECTIVE: The study aimed to assess the current management and follow-up of
      women with stage IA cervical cancer, according to the International Federation of
      Gynecology and Obstetrics, within the United Kingdom. DESIGN/SETTING: This study
      is a multicenter national audit of a clinical practice in the United Kingdom.
      MATERIALS AND METHODS: A structured questionnaire was sent and returned
      electronically to all lead colposcopists in the United Kingdom on the management
      and follow-up of women with stage IA cervical cancer according to the
      International Federation of Gynecology and Obstetrics. The study was approved by
      the British Society for Colposcopy and Cervical Pathology. RESULTS: Of the 210
      lead colposcopists, 110 (52%) responded. All reported that women with stage IA
      cervical cancer are discussed at a gynecologic multidisciplinary team meeting.
      Women who managed conservatively with their cervix in situ are followed up for at
      least 5 years. There is a wide variation in clinical management of cases with
      lymphovascular space involvement (LVSI) and depth of invasion greater than 3 mm
      (stage IA2). CONCLUSIONS: The pattern and practice of follow-up for stage IA
      cervical cancer is highly variable. The development of national guidance should
      be considered.

PMID- 22659776
TI  - Genital warts: Canadians' perception, health-related behaviors, and treatment
      preferences.
AB  - OBJECTIVE: The study aimed to gauge the perceptions of Canadians toward genital
      warts, related health behaviors, and treatment preferences. MATERIALS AND
      METHODS: An online survey supported by an unrestricted grant from Graceway Canada
      was conducted in February 2011 by Leger Marketing. It included 9 demographic
      questions and 17 questions relating to genital wart perception (2 multiple
      choice, 15 four-point rating from strongly agree to strongly disagree). RESULTS:
      The survey was completed by 1520 Canadian adults aged 18 to older than 75 years,
      of whom 52% (786/1520) were female. Fifty-two percent of respondents stated that
      they would monitor an unrecognized spot on their genitals, and only seek medical
      assistance if it did not go away. Only 43% (652/1520) said that they would stop
      having sex until the spots were gone. Although only 10% (158/1520) of respondents
      stated that they would not inform their partner, this was much higher among men
      (14%, 103/734) than women (7%, 55/786), with p <= .01. Concerns of being judged
      by friends/family were high (44%, 669/1520), especially among younger (18-34 y)
      Canadians (60%), with p <= .05. Regarding prevention, 32% (493/1520) of
      respondents believed that monogamy would protect against genital warts and 25%
      (373/1520) believed they are not at risk if they use a condom. Treatment
      preference was in favor of a cream rather than an "invasive" treatment (58%,
      886/1520), particularly among younger (67%, 283/425, p <= .05) and male
      respondents (63%, 464/734, p <= .01). Sixty percent (921/1520) would worry that
      genital warts could not be resolved; and 44% (668/1520), that they would recur.
      CONCLUSIONS: Among Canadians, genital warts were associated with a fair degree of
      social stigma and potential negative impact on their psyche, especially for
      younger Canadians.

PMID- 22659777
TI  - Secondary screening after primary self-sampling for human papillomavirus from
      SHENCCAST II.
AB  - OBJECTIVE: We recently demonstrated that a self-collected sample tested with a
      high-throughput polymerase chain reaction-based high-risk human papillomavirus
      (HR-HPV) assay is equal in sensitivity to a physician-obtained direct
      endocervical sample. We now explore some secondary screening options to improve
      specificity. METHODS: The Shenzhen Cervical Cancer Screening Trial II is a
      multisite, population-based cross-sectional cervical cancer screening study
      conducted in Guangdong Province, China. Two HR-HPV assays were used for self
      collected specimens, and 3 assays were used for directly collected specimens
      along with cytology. The polymerase chain reaction-based matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry assay reported 14 HR-HPV
      types. Any patient with a positive lesion on any assay or cytology underwent
      colposcopy and biopsy. RESULTS: A total of 8,556 women with a mean age of 38.9
      years (range = 25-54 years) were included in the analysis. Primary self
      collection had a sensitivity of 94.3% and a specificity of 87.5% (for cervical
      intraepithelial neoplasia grade 3 or cancer). Secondary cervical cytology had a
      sensitivity and specificity of 83.0% and 95.2%, respectively, which would require
      a pelvic examination and sacrifice some sensitivity. Secondary genotyping for HPV
      types 16 or 18 had a sensitivity and specificity of 53.9% and 97.7%,
      respectively; and HPV types 16, 18, 31, 33, 45, 52, and 58 had a sensitivity and
      specificity of 92.2% and 90.4%, respectively. CONCLUSIONS: Genotyping is
      efficient if it is part of the primary test result. It potentially identifies a
      high percentage of the cancers (types 16/18 = 84.5% in China).

PMID- 22659778
TI  - 2011 terminology of the vulva of the International Federation for Cervical
      Pathology and Colposcopy.
AB  - OBJECTIVE: This study aimed to present the clinical and colposcopic terminology
      of the vulva (including the anus) of the International Federation of Cervical
      Pathology and Colposcopy. MATERIALS AND METHODS: The terminology has been
      developed by the International Federation of Cervical Pathology and Colposcopy
      Nomenclature Committee during 2009-2011. RESULTS: The terminology is part of a
      comprehensive terminology of the lower genital tract, allowing for
      standardization of nomenclature by colposcopists, clinicians, and researchers
      taking care of women with lesions in these areas. The terminology includes basic
      definitions and normal findings that are important for the clinician lacking
      experience with management of vulvar disease. This terminology introduces
      definitions for abnormal findings recently accepted by the International Society
      for the Study of Vulvovaginal Disease and includes patterns to identify
      malignancy. CONCLUSIONS: The terminology differs from past terminologies in that
      it includes colposcopic patterns and anal colposcopy. Nevertheless, the role of
      the colposcope in the management of vulvar disease is limited.

PMID- 22659797
TI  - Star Trk(B): the astrocyte path to neurodegeneration.

PMID- 22659798
TI  - N-cadherin: a new player in neuronal polarity.

PMID- 22659796
TI  - Differential impact of structurally different anti-diabetic drugs on
      proliferation and chemosensitivity of acute lymphoblastic leukemia cells.
AB  - Hyperglycemia during hyper-CVAD chemotherapy is associated with poor outcomes of
      acute lymphoblastic leukemia (ALL) (Cancer 2004; 100: 1179-85). The optimal
      clinical strategy to manage hyperglycemia during hyper-CVAD is unclear. To
      examine whether anti-diabetic pharmacotherapy can influence chemosensitivity of
      ALL cells, we examined the impacts of different anti-diabetic agents on ALL cell
      lines and patient samples. Pharmacologically achievable concentrations of
      insulin, aspart and glargine significantly increased the number of ALL cells, and
      aspart and glargine did so at lower concentrations than human insulin. In
      contrast, metformin and rosiglitazone significantly decreased the cell number.
      Human insulin and analogs activated AKT/mTOR signaling and stimulated ALL cell
      proliferation (as measured by flow cytometric methods), but metformin and
      rosiglitazone blocked AKT/mTOR signaling and inhibited proliferation. Metformin
      500 MUM and rosiglitazone 10 MUM were found to sensitize Reh cells to
      daunorubicin, while aspart, glargine and human insulin (all at 1.25 mIU/L)
      enhanced chemoresistance. Metformin and rosiglitazone enhanced daunorubicin
      induced apoptosis, while insulin, aspart and glargine antagonized daunorubicin
      induced apoptosis. In addition, metformin increased etoposide-induced and L
      asparaginase-induced apoptosis; rosiglitazone increased etoposide-induced and
      vincristine-induced apoptosis. In conclusion, our results suggest that use of
      insulins to control hyperglycemia in ALL patients may contribute to anthracycline
      chemoresistance, while metformin and thiazolidinediones may improve
      chemosensitivity to anthracycline as well as other chemotherapy drugs through
      their different impacts on AKT/mTOR signaling in leukemic cells. Our data suggest
      that the choice of anti-diabetic pharmacotherapy during chemotherapy may
      influence clinical outcomes in ALL.

PMID- 22659808
TI  - Rosiglitazone inhibits angiotensin II-induced C-reactive protein production in
      human aortic endothelial cells through regulating AT(1)-ROS-MAPK signal pathway.
AB  - OBJECTIVE: Atherosclerosis is an inflammatory disease. As an inflammatory
      molecule, C-reactive protein (CRP) plays a direct role in atherogenesis. Our
      previous study confirmed that angiotensin II (Ang II) is capable of inducing CRP
      generation in human aortic endothelial cells (HAECs). The present study observed
      the effect of rosiglitazone on Ang II-induced CRP expression in HAECs and
      molecular mechanisms. METHODS: HAECs were cultured, and Ang II (10(-6) M) was
      used as a stimulant for the generation of CRP and reactive oxygen species (ROS).
      HAECs were preincubated with rosiglitazone at 1, 10, 100 uM for 18 h prior to the
      stimulation. mRNA and protein expressions were identified by reverse
      transcription polymerase chain reaction and Western blot, respectively. ROS
      production was observed by a fluorescence microscope. RESULTS: Pretreatment of
      HAECs with rosiglitazone prior to Ang II stimulation markedly downregulated Ang
      II-induced mRNA and protein expressions of CRP (maximal inhibition of 55.2 and
      99.1 %, P < 0.001 vs. Ang II alone) and AT(1) (maximal inhibition of 66.4 and
      90.5 %, P < 0.001 vs. Ang II alone) in a concentration-dependent manner,
      inhibited Ang II-stimulated ROS production (P < 0.01 vs. Ang II alone), and
      attenuated Ang II-induced phosphorylation of ERK1/2 and JNK (P < 0.001 vs. Ang II
      alone). Meanwhile, AT(1) receptor blocker losartan also reduced Ang II-stimulated
      ROS generation in HAECs (P < 0.001 vs. Ang II alone). CONCLUSIONS: Rosiglitazone
      at the concentrations used in the present experiment is able to inhibit Ang II
      induced CRP generation in HAECs by regulating AT(1)-ROS-MAPK signal pathway.
      These results strengthen our understanding of the anti-inflammatory and anti
      atherosclerotic effects of rosiglitazone.

PMID- 22659830
TI  - Synthesis of nano-sized anatase TiO2 with reactive {001} facets using lamellar
      protonated titanate as precursor.
AB  - Nano-sized anatase TiO(2) with exposed {001} facets was synthesized from lamellar
      protonated titanate precursor. Owing to small size (ca. 11 nm) and high surface
      area (155 m(2) g(-1)), the crystals with 26.1% {001} facets exhibited markedly
      superior photoactivity to reference ca. 76 nm anatase TiO(2) nanosheets with
      88.4% {001} facets.

PMID- 22659829
TI  - Alternating access mechanism in the POT family of oligopeptide transporters.
AB  - Short chain peptides are actively transported across membranes as an efficient
      route for dietary protein absorption and for maintaining cellular homeostasis. In
      mammals, peptide transport occurs via PepT1 and PepT2, which belong to the proton
      dependent oligopeptide transporter, or POT family. The recent crystal structure
      of a bacterial POT transporter confirmed that they belong to the major
      facilitator superfamily of secondary active transporters. Despite the functional
      characterization of POT family members in bacteria, fungi and mammals, a detailed
      model for peptide recognition and transport remains unavailable. In this study,
      we report the 3.3-A resolution crystal structure and functional characterization
      of a POT family transporter from the bacterium Streptococcus thermophilus.
      Crystallized in an inward open conformation the structure identifies a hinge-like
      movement within the C-terminal half of the transporter that facilitates opening
      of an intracellular gate controlling access to a central peptide-binding site.
      Our associated functional data support a model for peptide transport that
      highlights the importance of salt bridge interactions in orchestrating
      alternating access within the POT family.

PMID- 22659831
TI  - Ionization state of the catalytic dyad Asp25/25' in the HIV-1 protease: NMR
      studies of site-specifically 13C labelled HIV-1 protease prepared by total
      chemical synthesis.
AB  - Total chemical synthesis was used to site-specifically (13)C-label active site
      Asp25 and Asp25' residues in HIV-1 protease and in several chemically synthesized
      analogues of the enzyme molecule. (13)C NMR measurements were consistent with a
      monoprotonated state for the catalytic dyad formed by the interacting Asp25,
      Asp25' side chain carboxyls.

PMID- 22659832
TI  - Acetatifactor muris gen. nov., sp. nov., a novel bacterium isolated from the
      intestine of an obese mouse.
AB  - We used selective agar media for culturing bacteria from the caecum of mice fed a
      high calorie diet. In addition to the isolation of Enterobacteriaceae growing on
      a medium containing cholesterol and bile salts, we focused on the
      characterization of strain CT-m2(T), which, based on 16S rDNA analysis, did not
      appear to correspond to any currently described organisms. The isolate belongs to
      the Clostridium cluster XIV and is most closely related to members of the
      Lachnospiraceae, including the genera Anaerostipes, Blautia, Butyrivibrio,
      Clostridium, Coprococcus, Eubacterium, Robinsoniella, Roseburia, Ruminococcus and
      Syntrophococcus (<=90 % similarity). Strain CT-m2(T) is a non-motile Gram
      positive rod that does not form spores and has a G + C content of DNA of 48.5 %.
      Cells grow under strictly anoxic conditions (100 % N2) and produce acetate and
      butyrate after growth in reduced WCA broth. In contrast to related species, the
      new bacterium does not metabolize glucose and is positive for phenylalanine
      arylamidase, and its major cellular fatty acid is C14:0. Based on phylogenetic
      and phenotypic studies, the isolate merits recognition as a member of a novel
      genus and species, for which the name Acetatifactor muris is proposed. The type
      strain is CT-m2(T) (= DSM 23669(T) = ATCC BAA-2170(T)).

PMID- 22659838
TI  - Promoting evidence-based vaccine safety research and communication--the Vienna
      Vaccine Safety Initiative.

PMID- 22659839
TI  - Magnetic resonance imaging of optic neuritis in patients with neuromyelitis
      optica versus multiple sclerosis.
AB  - BACKGROUND: Patients with neuromyelitis optica (NMO) and multiple sclerosis (MS)
      both can present with acute optic neuritis (ON), while differing considerably in
      their prognosis and management. The clinical course, serologic testing results,
      and brain and spinal cord imaging of these diseases have been well documented.
      The purpose of this study was to look systematically for any differences in the
      imaging appearance of the optic nerve in NMO and MS-related ON. METHODS: Magnetic
      resonance imaging (MRI) of brain and orbits obtained within 6 weeks of acute ON
      in patients with securely diagnosed NMO (n = 6) and MS (n = 11) were
      retrospectively analyzed by a neuroradiologist masked to the clinical diagnosis.
      Standardized scoring system was used to assess and analyze the extent and nature
      of optic pathway involvement. RESULTS: No significant differences were observed
      in the presence, degree, or the type of signal alteration and contrast
      enhancement of the affected nerve segments between NMO and MS groups. There was a
      trend toward more posterior involvement of the optic nerve in the NMO group with
      chiasmatic enhancement exclusively seen in NMO patients. CONCLUSION: We found a
      higher propensity of NMO-related ON to affect more posterior parts of the optic
      nerve, including chiasm, and have simultaneous bilateral disease. Further study
      with larger sample sizes is needed.

PMID- 22659841
TI  - HIF-1 and its antagonist Cited2: regulators of HSC quiescence.

PMID- 22659842
TI  - Identification of novel metastasis suppressor signaling pathways for breast
      cancer.
AB  - Cancer lethality is mainly caused by metastasis. Therefore, understanding the
      nature of the genes involved in this process has become a priority. Given the
      heterogeneity of mutations in cancer cells, considerable focus has been directed
      toward characterizing metastasis genes in the context of relevant signaling
      pathways rather than treating genes as independent and equal entities. One
      signaling cascade implicated in the regulation of cell growth, invasion and
      metastasis is the MAP kinase pathway. Raf kinase inhibitory protein (RKIP)
      functions as an inhibitor of the MAP kinase pathway and is a metastasis
      suppressor in different cancer models. By utilizing statistical analysis of
      clinical data integrated with experimental validation, we recently identified
      components of the RKIP signaling pathway relevant to breast cancer metastasis.
      Using the RKIP pathway as an example, we show how prior biological knowledge can
      be efficiently combined with genome-wide patient data to identify gene regulatory
      mechanisms that control metastasis.

PMID- 22659843
TI  - Phospho-specific Smad3 signaling: impact on breast oncogenesis.
AB  - Members of the TGFbeta superfamily are known to exert a myriad of physiologic and
      pathologic growth controlling influences on mammary development and oncogenesis.
      In epithelial cells, TGFbeta signaling inhibits cell growth through cytostatic
      and pro-apoptotic activities but can also induce cancer cell EMT and, thus, has a
      dichotomous role in breast cancer biology. Mechanisms governing this switch are
      the subject of active investigation. Smad3 is a critical intracellular mediator
      of TGFbeta signaling regulated through phosphorylation by the TGFbeta receptor
      complex at the C terminus. Smad3 is also a substrate for several other kinases
      that phosphorylate additional sites within the Smad protein. This discovery has
      expanded the understanding of the significance and complexity of TGFbeta
      signaling through Smads. This review highlights recent advances revealing the
      critical role of phospho-specific Smad3 in malignancy and illustrates the
      potential prognostic and therapeutic impact of Smad3 phospho-isoforms in breast
      cancer.

PMID- 22659845
TI  - NK cells, hypoxia and trophoblast cell differentiation.
AB  - Hemochorial placentation is characterized by extensive remodeling of the maternal
      vasculature, converting them to flaccid low resistance vessels. This process
      greatly facilitates exchange of nutrients and gases between the mother and the
      fetus. Two key modulators that orchestrate these vascular changes have been
      identified at the maternal fetal interface, natural killer (NK) cells and
      invasive trophoblast cells. Hypoxia-inducible factor (HIF) transcription factors
      direct cellular responses to low oxygen, influencing trophoblast lineage
      commitment and promoting development of the invasive trophoblast lineage. This
      short review focuses on role of NK cells on uterine spiral artery development and
      subsequent modulation of oxygen tensions at the maternal fetal interface.

PMID- 22659844
TI  - Differential regulation of embryonic and adult beta cell replication.
AB  - Diabetes results from an inadequate functional beta cell mass, either due to
      autoimmune destruction (Type 1 diabetes) or insulin resistance combined with beta
      cell failure (Type 2 diabetes). Strategies to enhance beta cell regeneration or
      increase cell proliferation could improve outcomes for patients with diabetes.
      Research conducted over the past several years has revealed that factors
      regulating embryonic beta cell mass expansion differ from those regulating
      replication of beta cells post-weaning. This article aims to compare and contrast
      factors known to control embryonic and postnatal beta cell replication. In
      addition, we explore the possibility that connective tissue growth factor (CTGF)
      could increase adult beta cell replication. We have already shown that CTGF is
      required for embryonic beta cell proliferation and is sufficient to induce
      replication of embryonic beta cells. Here we examine whether adult beta cell
      replication and expansion of beta cell mass can be enhanced by increased CTGF
      expression in mature beta cells.

PMID- 22659858
TI  - Self-care: who cares?

PMID- 22659859
TI  - Cardiovascular disease: is it time to finally recognise it as a complex, chronic
      life-span illness?

PMID- 22659872
TI  - Structural diversity in native cyclodextrins/folic acid complexes--from [2]
      rotaxane to exclusion compound.
AB  - The formation of different complexes of folic acid depending on the size of the
      host cyclodextrin resulting in either an exclusion compound (with the smallest
      alpha-cyclodextrin) or 2-rotaxane, where cyclodextrin is threaded over folic acid
      (with beta- and gamma-cyclodextrins), is presented. The formation is carried out
      in water which allows both possible application in pharmaceutical sciences and
      usage of environmentally friendly "green chemistry". The obtained compounds are
      thoroughly characterized using one and two dimensional NMR, mass spectrometry,
      differential scanning calorimetry and thermogravimetric analysis.

PMID- 22659875
TI  - AMP-activated protein kinase undergoes nucleotide-dependent conformational
      changes.
AB  - The energy sensor AMP-activated protein kinase (AMPK) is a heterotrimeric complex
      that is allosterically activated by AMP binding to the gamma subunit. Cocrystal
      structures of the mammalian AMPK core reveal occlusion of nucleotide-binding site
      3 of the gamma subunit in the presence of ATP. However, site 3 is occupied in the
      presence of AMP. Mutagenesis studies indicate that sites 3 and 4 are important
      for AMPK allosteric activation.

PMID- 22659876
TI  - Duplex interrogation by a direct DNA repair protein in search of base damage.
AB  - ALKBH2 is a direct DNA repair dioxygenase guarding the mammalian genome against
      N(1)-methyladenine, N(3)-methylcytosine and 1,N(6)-ethenoadenine damage. A
      prerequisite for repair is to identify these lesions in the genome. Here we
      present crystal structures of human ALKBH2 bound to different duplex DNAs.
      Together with computational and biochemical analyses, our results suggest that
      DNA interrogation by ALKBH2 has two previously unknown features: (i) ALKBH2
      probes base-pair stability and detects base pairs with reduced stability, and
      (ii) ALKBH2 does not have nor need a damage-checking site, which is critical for
      preventing spurious base cleavage for several glycosylases. The demethylation
      mechanism of ALKBH2 insures that only cognate lesions are oxidized and reversed
      to normal bases, and that a flipped, non-substrate base remains intact in the
      active site. Overall, the combination of duplex interrogation and oxidation
      chemistry allows ALKBH2 to detect and process diverse lesions efficiently and
      correctly.

PMID- 22659877
TI  - Intronic RNAs mediate EZH2 regulation of epigenetic targets.
AB  - Epigenetic deregulation at a number of genomic loci is one of the hallmarks of
      cancer. A role for some RNA molecules in guiding repressive polycomb complex PRC2
      to specific chromatin regions has been proposed. Here we use an in vivo cross
      linking method to detect and identify direct PRC2-RNA interactions in human
      cancer cells, revealing a number of intronic RNA sequences capable of binding to
      the core component EZH2 and regulating the transcriptional output of its genomic
      counterpart. Overexpression of EZH2-bound intronic RNA for the H3K4
      methyltransferase gene SMYD3 is concomitant with an increase in EZH2 occupancy
      throughout the corresponding genomic fragment and is sufficient to reduce levels
      of the endogenous transcript and protein, resulting in reduced growth capability
      in cell culture and animal models. These findings reveal the role of intronic
      RNAs in fine-tuning gene expression regulation at the level of transcriptional
      control.

PMID- 22659878
TI  - NAD(P)H quinone oxidoreductase 1 regulates neutrophil elastase-induced mucous
      cell metaplasia.
AB  - Mucous cell metaplasia (MCM) and neutrophil-predominant airway inflammation are
      pathological features of chronic inflammatory airway diseases. A signature
      feature of MCM is increased expression of a major respiratory tract mucin,
      MUC5AC. Neutrophil elastase (NE) upregulates MUC5AC in primary airway epithelial
      cells by generating reactive oxygen species, and this response is due in part to
      upregulation of NADPH quinone oxidoreductase 1 (NQO1) activity. Delivery of NE
      directly to the airway triggers inflammation and MCM and increases synthesis and
      secretion of MUC5AC protein from airway epithelial cells. We hypothesized that NE
      induced MCM is mediated in vivo by NQO1. Male wild-type and Nqo1-null mice
      (C57BL/6 background) were exposed to human NE (50 MUg) or vehicle via
      oropharyngeal aspiration on days 1, 4, and 7. On days 8 and 11, lung tissues and
      bronchoalveolar lavage (BAL) samples were obtained and evaluated for MCM,
      inflammation, and oxidative stress. MCM, inflammation, and production of specific
      cytokines, granulocyte-macrophage colony-stimulating factor, macrophage
      inflammatory protein-2, interleukin-4, and interleukin-5 were diminished in NE
      treated Nqo1-null mice compared with NE-treated wild-type mice. However, in
      contrast to the role of NQO1 in vitro, we demonstrate that NE-treated Nqo1-null
      mice had greater levels of BAL and lung tissue lipid carbonyls and greater BAL
      iron on day 11, all consistent with increased oxidative stress. NQO1 is required
      for NE-induced inflammation and MCM. This model system demonstrates that NE
      induced MCM directly correlates with inflammation, but not with oxidative stress.

PMID- 22659880
TI  - Pulmonary intravascular macrophages as proinflammatory cells in heaves, an asthma
      like equine disease.
AB  - Heaves, an obstructive neutrophilic airway inflammation of horses, is triggered
      by dust components such as endotoxin and has similarities to human asthma.
      Pulmonary intravascular macrophages (PIMs) increase horses' sensitivity to
      endotoxin-induced lung inflammation; however, their role in an airborne pathology
      remains unknown. Therefore, we investigated the role of PIMs in the development
      of heaves in horses. Clinical and inflammatory responses were evaluated following
      induction of heaves by moldy hay exposure and PIM depletion with gadolinium
      chloride (GC). Mares (N = 9) were exposed to four treatments: alfalfa cubes (Cb),
      alfalfa cubes + GC (Cb-GC), moldy hay (MH), and moldy hay + GC (MH-GC). Clinical
      scores and neutrophil concentrations in bronchoalveolar lavage (BAL) fluid were
      higher when mares received MH compared with MH-GC. BAL cells from MH-GC-treated
      mares had significantly lower IL-8 and TLR4 mRNA expression compared with MH
      treated mares. In vitro LPS challenge significantly increased IL-8 but not TLR4
      mRNA expression in BAL cells recovered from horses fed with MH, but not from the
      MH-GC treatment. In summary, PIM depletion attenuated clinical scores, reduced
      the alveolar migration of neutrophils, and decreased the expression of
      proinflammatory molecules in BAL cells of heaves horses, suggesting a
      proinflammatory role of PIMs in the development of airborne pathology.

PMID- 22659879
TI  - Angiotensin II regulates activation of Bim via Rb/E2F1 during apoptosis:
      involvement of interaction between AMPKbeta1/2 and Cdk4.
AB  - Apoptotic cell death is essential for mammalian development and tissue
      homeostasis. Dysregulation of apoptosis has been identified in pathologies
      including in pulmonary fibrotic remodeling. We previously reported that a key
      proapoptotic factor in fibrosis, angiotensin II (Ang II), mediates apoptosis in
      primary pulmonary artery endothelial cells (PAEC) via the AT(2) receptor and
      requires activation of AMP-regulated protein kinase (AMPK). We now demonstrate
      that Ang II induces E2F1 transcription factor binding to and activation of the
      promoter for the Bcl-2 homology 3 (BH3)-only protein Bim. In PAEC, Ang II
      treatment induced cyclin-dependent kinase 4 (Cdk4)-mediated hyperphosphorylation
      of retinoblastoma protein (Rb) and its disassociation from E2F1, a key step in
      facilitating E2F1-directed transcriptional activity. Indeed, ectopic expression
      of a dominant negative Cdk4 mutant inhibited Ang II-mediated hyperphosphorylation
      of Rb and Bim promoter activation. Our data also show that the beta-subunit of
      AMPK was constitutively associated with Cdk4 in PAEC and that Ang II treatment
      induced AMPKbeta phosphorylation and subsequent disassociation of this complex.
      Both Ang II-induced Rb hyperphosphorylation and Cdk4-AMPK disassociation were
      blocked by the AMPK inhibitor compound C. Together these findings illuminate a
      novel proapoptotic signaling pathway in endothelial cells, whereby Ang II
      triggers E2F1-mediated transcriptional upregulation of Bim via activation of
      AMPKbeta1/2 and Cdk4.

PMID- 22659881
TI  - The adenosine 2A receptor agonist GW328267C improves lung function after acute
      lung injury in rats.
AB  - There is a significant unmet need for treatments of patients with acute lung
      injury (ALI) and/or acute respiratory distress syndrome (ARDS). The primary
      mechanism that leads to resolution of alveolar and pulmonary edema is active
      vectorial Na(+) and Cl(-) transport across the alveolar epithelium. Several
      studies have suggested a role for adenosine receptors in regulating this fluid
      transport in the lung. Furthermore, these studies point to the A(2A) subtype of
      adenosine receptor (A(2A)R) as playing a role to enhance fluid transport,
      suggesting that activation of the A(2A)R may enhance alveolar fluid clearance
      (AFC). The current studies test the potential therapeutic value of the A(2A)R
      agonist GW328267C to accelerate resolution of alveolar edema and ALI/ARDS in
      rats. GW328267C, at concentrations of 10(-5) M to 10(-3) M, instilled into the
      airspaces, increased AFC in control animals. GW328267C did not increase AFC
      beyond that produced by maximal beta-adrenergic stimulation. The effect of
      GW328267C was inhibited by amiloride but was not affected by cystic fibrosis
      transmembrane conductance regulator inhibition. The drug was tested in three
      models of ALI, HCl instillation 1 h, LPS instillation 16 h, and live Escherichia
      coli instillation 2 h before GW328267C instillation. After either type of injury,
      GW328267C (10(-4) M) decreased pulmonary edema formation and restored AFC,
      measured 1 h after GW328267C instillation. These findings show that GW328267C has
      beneficial effects in experimental models of ALI and may be a useful agent for
      treating patients with ALI or prophylactically to prevent ALI.

PMID- 22659882
TI  - Pulmonary microRNA profiling in a mouse model of ventilator-induced lung injury.
AB  - The aim of this study was to investigate the changes induced by high tidal volume
      ventilation (HVTV) in pulmonary expression of micro-RNAs (miRNAs) and identify
      potential target genes and corresponding miRNA-gene networks. Using a real-time
      RT-PCR-based array in RNA samples from lungs of mice subjected to HVTV for 1 or 4
      h and control mice, we identified 65 miRNAs whose expression changed more than
      twofold upon HVTV. An inflammatory and a TGF-beta-signaling miRNA-gene network
      were identified by in silico pathway analysis being at highest statistical
      significance (P = 10(-43) and P = 10(-28), respectively). In the inflammatory
      network, IL-6 and SOCS-1, regulated by miRNAs let-7 and miR-155, respectively,
      appeared as central nodes. In TGF-beta-signaling network, SMAD-4, regulated by
      miR-146, appeared as a central node. The contribution of miRNAs to the
      development of lung injury was evaluated in mice subjected to HVTV treated with a
      precursor or antagonist of miR-21, a miRNA highly upregulated by HVTV. Lung
      compliance was preserved only in mice treated with anti-miR-21 but not in mice
      treated with pre-miR-21 or negative-control miRNA. Both alveolar-arterial oxygen
      difference and protein levels in bronchoalveolar lavage were lower in mice
      treated with anti-miR-21 than in mice treated with pre-miR-21 or negative-control
      miRNA (D(A-a): 66 +/- 27 vs. 131 +/- 22, 144 +/- 10 mmHg, respectively, P <
      0.001; protein concentration: 1.1 +/- 0.2 vs. 2.3 +/- 1, 2.1 +/- 0.4 mg/ml,
      respectively, P < 0.01). Our results show that HVTV induces changes in miRNA
      expression in mouse lungs. Modulation of miRNA expression can affect the
      development of HVTV-induced lung injury.

PMID- 22659888
TI  - Presentation and management of Candida-associated vasculitis with
      gastrointestinal involvement in a pediatric patient.

PMID- 22659883
TI  - Improved throughput traction microscopy reveals pivotal role for matrix stiffness
      in fibroblast contractility and TGF-beta responsiveness.
AB  - Lung fibroblast functions such as matrix remodeling and activation of latent
      transforming growth factor-beta1 (TGF-beta1) are associated with expression of
      the myofibroblast phenotype and are directly linked to fibroblast capacity to
      generate force and deform the extracellular matrix. However, the study of
      fibroblast force-generating capacities through methods such as traction force
      microscopy is hindered by low throughput and time-consuming procedures. In this
      study, we improved at the detail level methods for higher-throughput traction
      measurements on polyacrylamide hydrogels using gel-surface-bound fluorescent
      beads to permit autofocusing and automated displacement mapping, and transduction
      of fibroblasts with a fluorescent label to streamline cell boundary
      identification. Together these advances substantially improve the throughput of
      traction microscopy and allow us to efficiently compute the forces exerted by
      lung fibroblasts on substrates spanning the stiffness range present in normal and
      fibrotic lung tissue. Our results reveal that lung fibroblasts dramatically alter
      the forces they transmit to the extracellular matrix as its stiffness changes,
      with very low forces generated on matrices as compliant as normal lung tissue.
      Moreover, exogenous TGF-beta1 selectively accentuates tractions on stiff
      matrices, mimicking fibrotic lung, but not on physiological stiffness matrices,
      despite equivalent changes in Smad2/3 activation. Taken together, these results
      demonstrate a pivotal role for matrix mechanical properties in regulating
      baseline and TGF-beta1-stimulated contraction of lung fibroblasts and suggest
      that stiff fibrotic lung tissue may promote myofibroblast activation through
      contractility-driven events, whereas normal lung tissue compliance may protect
      against such feedback amplification of fibroblast activation.

PMID- 22659889
TI  - KIT gene deletion in a gastrointestinal stromal tumor of the small intestine.

PMID- 22659890
TI  - Commentaries on "Workshop report: developing a pediatric inflammatory bowel
      diseases network and data platform in Canada": pediatric inflammatory bowel
      disease networks: raising the bar.

PMID- 22659891
TI  - Sacrificing the pulmonary arterial branch to the spared lobe is a risk factor of
      bronchopleural fistula in sleeve lobectomy after chemoradiotherapy.
AB  - OBJECTIVES: A sleeve lobectomy is a widely accepted procedure for enabling the
      pulmonary parenchyma to be spared. Induction chemoradiotherapy (CRT) followed by
      surgery is one treatment option for locally advanced non-small cell lung cancer
      (NSCLC), but CRT is considered to have a negative effect on subsequent surgery,
      especially for anastomotic healing. In this study, we describe our experience
      performing sleeve lobectomies and the associated anastomotic complications after
      induction CRT. METHODS: The medical records of NSCLC patients who underwent
      surgery after receiving CRT were reviewed. The relationships between anastomotic
      complications and clinicopathological factors were examined. RESULTS: Between
      December 1998 and October 2011, a total of 104 patients received CRT followed by
      surgery. Among them, 14 NSCLC patients underwent a bronchial sleeve resection:
      nine patients underwent a right upper lobe resection, two patients underwent a
      left lingular division and lower lobe resection and one patient each underwent a
      right lower lobe, a right upper and middle lobe and a right middle and lower lobe
      resection. A bronchopleural fistula at the anastomosis occurred in two patients.
      A pulmonary arterial (PA) branch to the spared lobe had been sacrificed in both
      of these patients because of tumour involvement. In contrast, the PA branches to
      the spared lobes were preserved in 11 of the 12 patients who did not exhibit
      anastomotic complications (P = 0.033). CONCLUSIONS: Our experience strongly
      suggests that the sacrifice of the PA branch to the spared lobe is a possible
      risk factor for anastomotic complications for a sleeve lobectomy after induction
      CRT.

PMID- 22659892
TI  - Cerebrovascular complications of left ventricular assist devices.
AB  - Left ventricular assist devices (LVADs) are increasingly being used as a bridge
      to heart transplantation or destination therapy. It is unclear which
      antithrombotic regimen should be used to reduce the risk of stroke. We
      systematically reviewed the literature on all types of antithrombotic regimens
      and stroke in patients with any type of LVADs. Our primary outcome measure was
      the mean incidence of any type of stroke. Twenty-six articles were selected as
      relevant, comprehending 1989 patients with a mean LVAD support of 200 days (range
      30-621). The mean proportion of patients affected with stroke was 20% (range 0
      55%), with a mean incidence of 0.74 (range 0-6.91) events/patient-year. Support
      with HeartMate II and a regimen of postoperative heparin converted to coumarins,
      acetylsalicylic acid (ASA) and dipyridamole resulted in 0.17 (mean; range 0.06
      0.29) strokes/patient-year. HeartMate II support and the same regime without
      heparin was associated with 0.07 (mean; range 0.03-0.11) strokes/patient-year. A
      Novacor device with heparin, converted to coumarins, was associated with 3.82
      (mean; range 1.03-6.91) strokes/patient-year, while ASA added to this regime
      resulted in 0.97 ischaemic strokes/patient-year (mean; range 0.53-1.48). Other
      combinations of assist devices and antithrombotic regimes were investigated in
      one or two studies only. This systematic review provides risk estimates for
      stroke for various LVADs and antithrombotic regimes. Our findings indicate that
      the postoperative use of heparin in HeartMate II patients is doubtful, and
      suggest an important role for antiplatelet drugs to prevent stroke in patients
      supported with a Novacor device.

PMID- 22659893
TI  - Extracardiac Fontan with direct cavopulmonary connections: midterm results.
AB  - OBJECTIVES: The aim of this study was to analyse the midterm results following
      superior and inferior direct cavopulmonary connections (DCPC) to create a Fontan
      circulation in patients with functionally univentricular hearts. METHODS: A
      retrospective review of patients operated on between January 2005 and December
      2011 was carried out. RESULTS: Thirty consecutive patients who underwent this
      type of operation were retrospectively reviewed. There were 18 (60%) males and 12
      (40%) females, with a median age of 69 months (range 16-150 months) and median
      weight of 23 kg (range 11-46 kg). Aortic cross-clamping was used in 10 patients,
      with a median cross-clamp time of 40 min (range 23-99) and a median
      cardiopulmonary bypass (CPB) time of 135 min (range 76-179 min). The remaining 20
      patients were operated on without aortic cross-clamping. Their median CPB time
      was 104 min (range 78-139 min). Fenestration was performed in 16 patients. The
      associated intracardiac procedures were performed in 10 patients. The follow-up
      period ranged from 2 months to 6 years. Operative mortality and late mortality
      after discharge was zero. The major postoperative complications included
      supraventricular tachycardia in one patient, oliguria and peritoneal dialysis in
      one and chest drainage (>30 ml/day) persisting >7 days in five (20%). One patient
      developed sinus bradycardia in association with sinus pauses 2 months after
      discharge. One patient developed pericardial effusion 1 month after discharge. A
      computational fluid dynamic study was performed in one patient. The computational
      fluid dynamic study showed that DCPC may have a better power efficiency.
      CONCLUSIONS: Superior and inferior DCPCs to create a Fontan circulation in
      appropriately selected patients with functionally univentricular hearts can be
      performed with a low risk and a low rate of reinterventions. The midterm results
      are favourable.

PMID- 22659894
TI  - Emergency pericardiocentesis: a word of caution! Accidental transhepatic
      intracardiac placement of a pericardial catheter.

PMID- 22659895
TI  - Surgical conversion early after failed percutaneous repair with the MitraClip
      system.

PMID- 22659896
TI  - Yesterday's future: the gap between where we are now and where we were supposed
      to be.

PMID- 22659897
TI  - Self-inflicted intracardiac sewing needle.

PMID- 22659898
TI  - Video-assisted thoracoscopic removal of pulmonary hydatid cysts.
AB  - OBJECTIVES: Pulmonary hydatid disease is a parasitic disease with a high
      prevalence in low-middle income countries. We report four patients who were
      treated surgically using video-assisted thoracoscopy (VATS). METHODS: All
      patients were diagnosed with clinical and radiological findings on chest X-ray
      and computed tomography. Complete thoracoscopic removal by cystotomy and
      capitonnage was done in all four patients. The procedure included a standard
      thoracoscopy port incision and a 2-3 cm utility skin incision that was placed
      just superior to the cystic lesion. In the first case, a small-sized rib
      separator was used. The following three cases were operated without placing a rib
      separator on the utility incision. Conversion to open thoracotomy was not
      required. RESULTS: The average duration of the procedure was 90 min, and the
      average length of hospital stay was 4 days. No complications were observed after
      the thoracoscopic removal. At mean follow-up of 4 months, all patients were
      asymptomatic. CONCLUSIONS: VATS removal of the hydatid cysts can be done
      successfully in peripherally located cysts.

PMID- 22659899
TI  - Right ventricular laceration caused by an intact sternal wire: a rare
      complication of median sternotomy.

PMID- 22659900
TI  - Intrathoracic costal exostosis.

PMID- 22659916
TI  - The ins and outs of human reticulocyte maturation: autophagy and the
      endosome/exosome pathway.
AB  - The maturation of reticulocytes into functional erythrocytes is a complex process
      requiring extensive cytoplasmic and plasma membrane remodeling, cytoskeletal
      rearrangements and changes to cellular architecture. Autophagy is implicated in
      the sequential removal of erythroid organelles during erythropoiesis, although
      how this is regulated during late stages of erythroid differentiation, and the
      potential contribution of autophagy during reticulocyte maturation, remain
      unclear. Using an optimized ex vivo differentiation system for human
      erythropoiesis, we have observed that maturing reticulocytes are characterized by
      the presence of one or few large vacuolar compartments. These label strongly for
      glycophorin A (GYPA/GPA) which is internalized from the plasma membrane; however,
      they also contain organellar remnants (ER, Golgi, mitochondria) and stain
      strongly for LC3, suggesting that they are endocytic/autophagic hybrid
      structures. Interestingly, we observed the release of these vacuoles by
      exocytosis in maturing reticulocytes, and speculate that autophagy is needed to
      concentrate the final remnants of the reticulocyte endomembrane system in
      autophagosome/endosome hybrid compartments that are primed to undergo exocytosis.

PMID- 22659922
TI  - Clinical value of blood glucose measurement in pet rabbits.
AB  - Blood glucose was measured with a portable glucose meter in 907 rabbits,
      including 238 clinically healthy ones. Blood glucose concentrations ranged from
      1.2 to 30.1 mmol/l. Diabetes mellitus was not encountered. No significant effect
      of sex or sedation was found. Hypoglycaemia was seen in 16 rabbits including one
      with an insulinoma. There was a significant relationship between blood glucose,
      food intake, signs of stress and severity of clinical disease. Rabbits showing
      signs of stress had higher blood glucose than rabbits with no signs and rabbits
      that were totally anorexic had higher blood glucose values than those that were
      eating normally or those with reduced food intake. Severe hyperglycaemia (>20
      mmol/l) was associated with conditions with a poor prognosis. Rabbits with
      confirmed intestinal obstruction had a mean blood glucose of 24.7 mmol/l (n=18).
      This was significantly higher than the rabbits with confirmed gut stasis, which
      had a mean value of 8.5 mmol/l (n=51). The conclusion of the study was that blood
      glucose is a measurable parameter that can be used to assess the severity of a
      rabbit's condition and help to differentiate between gut stasis and intestinal
      obstruction in rabbits that are anorexic.

PMID- 22659923
TI  - Acute phase protein levels in dogs with mast cell tumours and sarcomas.
AB  - The acute phase proteins (APP) form part of a non-specific host response to
      inflammation. They may be induced by a range of different causes, including
      infection, inflammation, cancer and trauma. As they form part of the earliest
      response to such insults, they have potential for early identification of
      disease. In people, APP levels have been shown to correlate both with the extent
      of disease and also the prognosis in several forms of neoplasia, including
      prostate, oesophageal and colorectal cancer. As such, they can be used as
      prognostic and monitoring tools. To date, similar studies in veterinary patients
      have been limited, largely retrospective in nature and many are non-specific for
      tumour type. The purpose of this study was to evaluate a panel of four APPs in
      dogs with naturally occurring mast cell tumours (MCTs) and sarcomas to identify
      in the first instance whether increased levels of individual APPs, or
      identifiable combinations of APPs, was linked with the presence of disease. In
      the patients with MCTs, C-reactive protein (CRP) and alpha-1 acid glycoprotein
      levels increased, with a concurrent drop in serum amyloid A levels. In the
      sarcoma patients, CRP, alpha-1 acid glycoprotein and haptoglobin were increased.
      These findings suggest that specific solid tumour types in dogs may be associated
      with specific changes in APP profiles.

PMID- 22659939
TI  - Muscular exercise capacity and body fat predict VO(2peak) in heart transplant
      recipients.
AB  - BACKGROUND: Heart transplant (HTx) recipients usually have reduced exercise
      capacity, with reported VO2peak levels of 50-70% of predicted values. This study
      aimed to evaluate central and peripheral factors predictive of VO2peak. METHODS
      AND RESULTS: Fifty-one clinically stable HTx recipients >18 years old and 1-8
      years after HTx, underwent maximal exercise testing on a treadmill. Clinical
      laboratory, haemodynamic and echocardiographic data, lung function, and
      isokinetic muscle strength and muscular exercise capacity were recorded. The mean
      +/- SD age was 52 +/- 16 years, 71% were male, and time from HTx was 4.1 +/- 2.2
      years. The patients were assigned to one of two groups: VO2peak <=or >27.3
      ml/kg/min, which was the median value, corresponding to 80% of predicted value.
      The group with the higher VO2peak had significantly lower body mass index, body
      fat, and triglycerides, and significantly higher body water, muscular exercise
      capacity, high-density lipoprotein (HDL) cholesterol, lung function, mitral
      annular velocity, peak ventilation, O2 pulse, and VE/VCO2 slope. Donor age,
      recipient age, sex, medication, ischaemic time, cardiac dimensions, systolic
      function, and chronotropic responses during exercise were similar. Multiple
      regression analysis showed that muscular exercise capacity and body fat were the
      strongest VO2peak predictors. CONCLUSIONS: Chronotropic incompetence is not a
      limiting factor for exercise capacity in a population of relatively fit HTx
      patients. The most significant predictors, representing only peripheral factors,
      are similar to those often determining VO2peak in healthy, non-athletic
      individuals. Our findings emphasize the importance of a low percentage of body
      fat and high muscular exercise capacity in order to attain a sufficient VO2peak
      level after HTx.

PMID- 22659940
TI  - Regulation of uterine AHR battery gene expression by 17beta-Estradiol is
      predominantly mediated by estrogen receptor alpha.
AB  - The aryl hydrocarbon receptor (AHR) is known to mediate the cellular response to
      numerous xenobiotics including dioxin. Surprisingly AHR knockout mice provide
      evidence for the involvement of the AHR signalling cascade in estrogen regulated
      physiological functions of the female reproductive system. Several studies
      already aimed to investigate the impact of the AHR mediated xenobiotic response
      pathway on estrogen receptor (ER) signalling, whereas on contrary availability of
      data describing the effect of 17beta-Estradiol (E2) on the AHR signalling cascade
      is rather limited. In this study we observed an inhibitory effect of E2 treatment
      on uterine Ahr, Arnt, Arnt2, Ahrr, Cyp1a1, Ugt1 and Nfe2l2 gene expression in
      ovariectomized Wistar rats, whereas Cyp1b1, Nqo1 and Gsta2 displayed an increased
      transcription. The usage of the ER selective agonists, 16alpha-LE(2) (ERalpha
      selective) and 8beta-VE(2) (ERbeta selective), enabled us to distinguish between
      ER subtype specific responses. On mRNA level the observed changes in gene
      expression were mainly mediated by ERalpha except for the expression of Nqo1. In
      most cases the activation of ERbeta caused effects opposite to the ones observed
      following activation of ERalpha. Despite the significant changes in AHR mRNA
      levels immunohistochemical staining uterine tissue section did not reveal changes
      of the AHR protein level. Taken together our results validate, support and extend
      the hypothesis of uterine crosstalk between AHR and ER signalling pathways.
      Furthermore they give an insight into how the AHR and its related genes may
      participate in E2 dependent uterine physiological processes and provide another
      potential mechanism of action for xenoestrogens.

PMID- 22659941
TI  - Excitation energy transfer in multiporphyrin arrays with cyclic architectures:
      towards artificial light-harvesting antenna complexes.
AB  - Since highly symmetric cyclic architecture of light-harvesting antenna complex
      LH2 in purple bacteria was revealed in 1995, there has been a renaissance in
      developing cyclic porphyrin arrays to duplicate natural systems in terms of high
      efficiency, in particular, in transferring excitation energy. This tutorial
      review highlights the mechanisms and rates of excitation energy transfer (EET) in
      a variety of synthetic cyclic porphyrin arrays on the basis of time-resolved
      spectroscopic measurements performed at both ensemble and single-molecule levels.
      Subtle change in structural parameters such as connectivity, distance, and
      orientation between neighboring porphyrin moieties exquisitely modulates not only
      the nature of interchromophoric interactions but also the rates and efficiencies
      of EET. The relationship between the structure and EET dynamics described here
      should assist a rational design of novel cyclic porphyrin arrays, more contiguous
      to real applications in artificial photosynthesis.

PMID- 22659943
TI  - [Total mesorectal excision with and without preoperative radiotherapy for
      patients with resectable rectal cancer: The multicentre, randomised controlled
      TME trial 12-year follow-up].

PMID- 22659942
TI  - Impact of intensity-modulated and image-guided radiotherapy on elderly patients
      undergoing chemoradiation for locally advanced head and neck cancer.
AB  - PURPOSE: In this work, the treatment tolerance of elderly patients (>=70 years)
      undergoing intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy
      (IGRT) and chemotherapy for locally advanced head and neck cancer was assessed.
      PATIENTS AND METHODS: A retrospective review of 112 patients undergoing
      concurrent chemoradiation for locally advanced head and neck cancer was
      performed. Treatment toxicity, protocol violations, long-term complications, and
      survival were compared between 85 younger patients (< 70 years) and 27 older
      patients (>= 70 years). RESULTS: Grade 3-4 treatment toxicity was observed in
      88.2% and 88.8% for younger and older patients, respectively. Mean weight loss
      and treatment break were 5.9 and 3.9 kg (p = 0.03) and 7.3 and 7.8 days (p = 0.8)
      for younger and older patients, respectively. Seven patients (8.2%) did not
      complete treatment in the younger group compared to 1 patient (3.7%) in the older
      group (p = 0.6). No significant differences in protocol violations and survival
      were found between the two groups. CONCLUSION: Compared to younger patients,
      elderly patients with locally advanced head and neck cancer tolerated
      chemoradiation with IMRT and IGRT well, and should not be denied curative
      treatment based solely on age.

PMID- 22659944
TI  - Kinetic and analytical study of the photo-induced degradation of monuron by
      nitrates and nitrites under irradiation or in the dark.
AB  - The photo-induced transformation of monuron (3-(4-chlorophenyl)-1,1 dimethylurea)
      was investigated in an aqueous solution containing nitrates and nitrites at 310
      nm and 365 nm, respectively. In both NO(3)(-) and NO(2)(-) conditions, the
      degradation of monuron followed pseudo-first order kinetics. The intermediate
      products were identified by GC-MS, and the nitration, hydroxylation and coupling
      reactions were determined. In addition, the oxidation of the N-terminus group,
      the substitution of chlorine by OH and the nitration by NO(2) radical onto the
      phenyl ring were observed. The photo-induced transformation of monuron was
      studied under variable conditions of pH, inducer concentration, substrate
      concentration, humic acids, oxygen content and salts used as hydroxyl radical
      scavengers. The photodegradation rates were strongly influenced by all the above
      parameters. The degradation of monuron was also studied in the dark and in the
      presence of NO(2)(-) as well as in an aqueous solution with the addition of
      hydrogen peroxide.

PMID- 22659950
TI  - The prevalence of pulmonary embolism in chronic spinal cord lesioned individuals.

PMID- 22659960
TI  - Tumor cavitation in patients with stage III non-small-cell lung cancer undergoing
      concurrent chemoradiotherapy: incidence and outcomes.
AB  - INTRODUCTION: Commonly reported complications after concurrent chemoradiotherapy
      (CCRT) in patients with stage III non-small-cell lung cancer (NSCLC) include
      febrile neutropenia, radiation esophagitis, and pneumonitis. We studied the
      incidence of tumor cavitation and/or "tumor abscess" after CCRT in a single
      institutional cohort. METHODS: Between 2003 and 2010, 87 patients with stage III
      NSCLC underwent cisplatin-based CCRT and all subsequent follow-up at the VU
      University Medical Center. Diagnostic and radiotherapy planning computed
      tomography scans were reviewed for tumor cavitation, which was defined as a
      nonbronchial air-containing cavity located within the primary tumor. Pulmonary
      toxicities scored as Common Toxicity Criteria v3.0 of grade III or more,
      occurring within 90 days after end of radiotherapy, were analyzed. RESULTS: In
      the entire cohort, tumor cavitation was observed on computed tomography scans of
      16 patients (18%). The histology in cavitated tumors was squamous cell (n = 14),
      large cell (n = 1), or adenocarcinoma (n = 1). Twenty patients (23%) experienced
      pulmonary toxicity of grade III or more, other than radiation pneumonitis. Eight
      patients with a tumor cavitation (seven squamous cell carcinoma) developed severe
      pulmonary complications; tumor abscess (n = 5), fatal hemorrhage (n = 2), and
      fatal embolism (n = 1). Two patients with a tumor abscess required open-window
      thoracostomy post-CCRT. The median overall survival for patients with or without
      tumor cavitation were 9.9 and 16.3 months, respectively (p = 0.09). CONCLUSIONS:
      With CCRT, acute pulmonary toxicity of grade III or more developed in 50% of
      patients with stage III NSCLC, who also had radiological features of tumor
      cavitation. The optimal treatment of patients with this presentation is unclear
      given the high risk of a tumor abscess.

PMID- 22659961
TI  - Clinical and pathological characteristics, outcome and mutational profiles
      regarding non-small-cell lung cancer related to wood-smoke exposure.
AB  - HYPOTHESIS: Although smoking is the major risk factor for non-small-cell lung
      cancer (NSCLC), other factors are also associated with lung carcinogenesis, such
      as wood-smoke exposure (WSE). This article has been aimed at suggesting that lung
      cancer related to cigarette smoking and lung cancer related to WSE have different
      clinical and genetic characteristics. EXPERIMENTAL DESIGN: A cohort of 914 lung
      cancer patients was prospectively studied; they had been treated at Mexico's
      National Cancer Institute between 2007 and 2010. The associations of WSE and
      cigarette smoking with clinical characteristics, mutation profile, response to
      chemotherapy, and epidermal growth factor receptor tyrosine kinase inhibitors
      were analyzed, and overall survival (OS) rate was calculated. The trial was
      registered with ClinicalTrials.gov: NCT01023828. RESULTS: Of the lung cancer
      patients studied, 95.1% were classified as coming within the NSCLC histology
      subtype; 58% of the patients smoked cigarettes, 35% had a background of WSE
      (exposure to both cigarette smoke and wood smoke was documented in 12.1% of all
      patients), and 19.4% patients had no smoke-exposure background. WSE was
      associated with NSCLC and adenocarcinoma histology, and was also more frequently
      associated with epidermal growth factor receptor-mutations than cigarette-smoking
      patients were (50.0% cf. 19.4%), whereas KRAS mutations were less common in WSE
      patients (6.7%) than in smokers (21%). WSE patients had a higher epidermal growth
      factor receptor tyrosine kinase inhibitor response rate (39.7%) than smokers
      (18.8%). The NSCLC patient WSE group's OS was longer (22.7 months) than that for
      smokers (13.8 months). CONCLUSION: NSCLC patients who smoked tobacco/cigarettes
      differed from those having a background of WSE regarding tumor histology,
      mutation profile, response rate, and OS, indicating that different carcinogenic
      mechanisms were induced by these two types of smoke exposure.

PMID- 22659962
TI  - Predictive risk factors for mediastinal lymph node metastasis in clinical stage
      IA non-small-cell lung cancer patients.
AB  - INTRODUCTION: Even for patients with clinical N0 non-small-cell lung cancer
      (NSCLC), several invasive tests are available to pathologically confirm the
      presumptive mediastinal stage by radiologic modalities. The aim of this study was
      to determine a high-risk population for mediastinal nodal metastasis in patients
      with clinical stage IA NSCLC, which would be suitable for mediastinal staging by
      invasive modalities, such as mediastinoscopy or endobronchial ultrasound-guided
      transbronchial needle aspiration. METHODS: We retrospectively reviewed peripheral
      clinical stage IA NSCLC patients who had undergone surgical resection with
      systematic mediastinal lymphadenectomy from 1998 to 2011. To identify predictors
      for mediastinal nodal metastasis, univariate and multivariate logistic regression
      analyses were performed. For the significant factors, optimal cutoff points were
      determined with a receiver operating characteristic analysis. RESULTS: Among the
      894 patients eligible for this study, the overall prevalence of mediastinal nodal
      metastasis was 7.5%. The following four predictors for mediastinal nodal
      metastasis were identified: age, preoperative serum carcinoembryonic antigen
      level, tumor size on preoperative radiologic findings, and consolidation/tumor
      ratio on high-resolution computed tomography. Of the patients with all four
      predictors identified by the multivariate analyses and receiver operating
      characteristic analyses (age <= 67 years, carcinoembryonic antigen >= 3.5 ng/ml,
      tumor size >= 2.0 cm, and consolidation/tumor ratio >= 89%), the prevalence of
      mediastinal nodal metastasis was 33.8%. CONCLUSIONS: Among the clinical stage IA
      NSCLC patients in whom all four predictors were identified, one third of the
      patients showed mediastinal nodal metastasis, and thus, those patients should be
      a target for mediastinal node assessment by invasive modalities, such as
      mediastinoscopy or endobronchial ultrasound-guided transbronchial needle
      aspiration.

PMID- 22659963
TI  - Maintenance therapy for advanced non-small-cell lung cancer: a pilot study on
      patients' perceptions.
AB  - INTRODUCTION: Several randomized trials on maintenance therapy (MT) for
      metastatic non-small-cell lung cancer (NSCLC) have demonstrated benefit in
      progression-free survival. More recently, a study with pemetrexed and one with
      erlotinib also showed significant gains in overall survival (OS). Yet, in this
      palliative treatment setting, the benefit has to be weighed against the potential
      burden of treatment, and thus patients' preferences should be taken into account.
      METHODS: In the absence of data on this topic, we undertook a pilot survey with
      10 questions covering the overall patient attitude toward MT, the benefit
      expected by patients, and the acceptance of side effects or modes of
      administration. Included patients had stage IV NSCLC and were planned to start
      first-line platinum-based doublet chemotherapy. The questionnaire was submitted
      at the start of and after two and four cycles of chemotherapy. RESULTS: Thirty
      patients were included. Overall, patients had a positive attitude toward MT. At
      baseline, it was considered worthwhile by 83%, 67%, and 43% of patients for an OS
      benefit of 6, 3, or 1 month, respectively, with some decrease over time. Effects
      on symptom control were crucial for about 90% of the patients. There was a slight
      preference for oral versus intravenous administration. Side effects were accepted
      by most patients as long as they were mild to moderate. CONCLUSION: Our pilot
      survey showed that metastatic NSCLC patients in general are in favor of MT. They
      expect either an OS benefit of at least several months, or better symptom
      control, in balance with mild-to-moderate side effects.

PMID- 22659964
TI  - Gefitinib enhances cytotoxicities of antimicrotubule agents in non-small-cell
      lung cancer cells exhibiting no sensitizing epidermal growth factor receptor
      mutation.
AB  - INTRODUCTIONS: Although randomized clinical trials showed no benefit from
      combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs) with standard chemotherapy for advanced non-small-cell lung cancer
      (NSCLC), better results might be obtained by combining EGFR-TKI with individual
      agents that are substrates for the adenosine triphosphate binding cassette
      transporters (ABCTs) because EGFR-TKIs can inhibit their efflux. The combination
      effects deserved to be further examined in vitro. METHODS: The combination
      effects of gefitinib with three antimicrotubule agents (AMTAs), paclitaxel,
      docetaxel or vinorelbine, or with gemcitabine were tested in 17 NSCLC cell lines
      using the tetrazolium colorimetric assay and classical isobole method. The
      effects of drug combinations, identified by the values of mean combination index
      (mCIs), were correlated with the expression levels of ABCTs. Dose-versus-log
      response curves were analyzed to further evaluate the possible mechanisms of drug
      interactions. RESULTS: Synergistic gefitinib/AMTA interactions were observed in
      the tested cell lines. The synergism was more robust in the four lines
      overexpressing de novo or acquired P-glycoprotein (Pgp; individual mCIs range,
      0.484-0.859; all p values were < 0.05), or in 12 cell lines exhibiting no
      sensitizing EGFR mutations (group mCIs for gefitinib/paclitaxel,
      gefitinib/docetaxel, and gefitinib/vinorelbine were 0.869, 0.82, and 0.853,
      respectively. All p values were < 0.02). The synergism could be observed in cells
      expressing nearly undetectable Pgp and other ABCTs tested in this study. The
      combination of gefitinib/gemcitabine was additive (mCI = 1.027). CONCLUSIONS:
      Combined gefitinib/AMTAs showed synergism in NSCLC cells harboring no sensitizing
      EGFR mutations. Gefitinib could enhance AMTA effects through mechanisms not
      restricted to Pgp blockage.

PMID- 22659976
TI  - Dysregulation of kappa-opioid receptor systems by chronic nicotine modulate the
      nicotine withdrawal syndrome in an age-dependent manner.
AB  - RATIONALE: Mechanisms that mediate age differences during nicotine withdrawal are
      unclear. OBJECTIVE: This study compared kappa-opioid receptor (KOR) activation in
      naive and nicotine-treated adolescent and adult rats using behavioral and
      neurochemical approaches to study withdrawal. METHODS: The behavioral models used
      to assess withdrawal included conditioned place and elevated plus maze
      procedures. Deficits in dopamine transmission in the nucleus accumbens (NAcc)
      were examined using microdialysis procedures. Lastly, the effects of KOR
      stimulation and blockade on physical signs produced upon removal of nicotine were
      examined in adults. RESULTS: Nicotine-treated adults displayed a robust aversion
      to an environment paired with a KOR agonist versus naive adults. Neither of the
      adolescent groups displayed a place aversion. KOR activation produced an increase
      in anxiety-like behavior that was highest in nicotine-treated adults versus all
      other groups. KOR activation produced a decrease in NAcc dopamine that was
      largest in nicotine-treated adults versus all other groups. Lastly, KOR
      activation facilitated physical signs of withdrawal upon removal of nicotine and
      KOR blockade reduced this effect. CONCLUSION: Chronic nicotine enhanced the
      affective, anxiogenic, and neurochemical effects produced by KOR activation in
      adult rats. Our data suggest that chronic nicotine elicits an increase in KOR
      function, and this may contribute to nicotine withdrawal since KOR activation
      facilitated and KOR blockade prevented withdrawal signs upon removal of nicotine.
      Given that chronic nicotine facilitated the neurochemical effects of KOR agonists
      in adults but not in adolescents, it is suggested that KOR regulation of
      mesolimbic dopamine may contribute to age differences in nicotine withdrawal.

PMID- 22659977
TI  - [Nutrition in intensive care medicine].
AB  - Nutrition of intensive care patients is challenging due to complex metabolic
      changes. For this reason nutritional support adapted to the metabolic state is
      the only effective option to avoid hyperalimentation or hypoalimentation and thus
      has a direct influence on the prognosis. The analysis of the calorific
      requirement and the mode of administration are of key importance. An early
      enteral nutrition should be established, whereas in practice often a
      supplementary parenteral support is required to provide adequate calorie supply.
      Nowadays, most commercially available standard solutions are optimized concerning
      composition of nutrients; however, metabolic and gastrointestinal monitoring is
      recommended. In a selected group of patients the administration of
      immunomodulatory substances may be indicated but due to insufficient or
      conflicting study data an uncritical use of these supplements cannot be
      recommended.

PMID- 22659988
TI  - Diet quality and social support: factors associated with serum carotenoid
      concentrations among older disabled women (the Women's Health and Aging Study).
AB  - PURPOSE: This study investigated the relationship between social support
      (including instrumental support, emotional support, social interaction, social
      space, and family networks) and diet quality, as indicated by serum carotenoid
      levels. DESIGN AND METHODS: The sample consisted of participants in the Women's
      Health and Aging Study with longitudinal carotenoid data (n=325). We performed
      regression analyses using baseline indicators of social support and changes in
      social support to determine whether baseline levels and/or change in levels of
      social support predict changes in serum carotenoid levels. Social support changes
      were measured over 1 year from baseline to follow-up round 1. Carotenoid level
      changes were established from follow-up round 1 to round 2. To determine whether
      or not regression to the mean was driving these results, we performed an analysis
      that included baseline and change levels of social support indicators. RESULTS:
      At baseline, the frequency of leaving one's home was associated with a decrease
      in carotenoid levels. Leaving one's home more frequently predicted an increase in
      carotenoid levels and attending fewer activities predicted a decrease in
      carotenoid levels. IMPLICATIONS: In older, community-resident disabled women,
      baseline levels of social support did not consistently predict diet quality.
      However, change in social support predicted both positive and negative change in
      diet quality and thus provides supportive evidence that social activity and
      family interaction may play meaningful roles in the maintenance of diet quality
      among functionally compromised older women. Further research is necessary to more
      fully understand the impact of multiple forms of social supports on the diet
      quality of older adults.

PMID- 22659989
TI  - Survival benefits of metabolic syndrome among older men aged 75 years and over in
      Taiwan.
AB  - BACKGROUND: Metabolic syndrome (MetS) was common in the elderly, but its
      prognostic significance in older old population remained unclear. The main
      purpose of this study was to evaluate the survival impact of MetS among older men
      aged 75 and over in Taiwan. METHODS: From 2008, residents aged 75 years and older
      of Banciao Veterans Home were invited for study and were followed for 3 years.
      All participants received history taking, physical examinations, and laboratory
      tests. Mortality was determined by Veteran Affairs Death Registry, which was
      linked to the National Death Registry. RESULTS: Overall, 680 men (mean age:
      82.5+/-4.7 years) were enrolled for study and the prevalence of MetS was 31.6%.
      During the follow-up period, 140 (20.6%) participants died, and the causes of
      death included infectious diseases (62, 9.1%), cardiovascular disease (37, 5.4%),
      cancer (20, 2.9%), and others (21, 3.1%). MetS subjects had a significantly
      higher prevalence of hypertension, diabetes mellitus, and having higher body mass
      index, waist circumferences, systolic blood pressure, fasting blood glucose,
      serum triglyceride and lower HDL-C level than non-MetS subjects. However, MetS
      subjects were less likely to die during study period (16.3% vs. 22.6%, P=0.059).
      Multivariate logistic regression showed that older age (OR:1.04, 95% C.I.: 1.00
      1.08, P=0.04), diabetes mellitus (OR: 2.10, 95% CI: 1.34-3.30, P=0.001) were
      independent risk factors for mortality; and serum total cholesterol and
      triglyceride were protective factors (OR: 0.99, 95% CI: 0.99-1.00, P=0.037 for
      cholesterol; OR: 0.99, 95% CI: 0.99-1.00, P=0.013 for triglyceride). Adjusted for
      age, diabetes mellitus, serum levels of total cholesterol, and triglyceride, MetS
      played a potential trend of survival benefits among study subjects (HR: 0.71, 95%
      CI: 0.45-1.12, P=0.144). CONCLUSIONS: The prevalence of MetS among men aged 75
      years and over was 31.6%, and the 3-year mortality rate was 20.6%. Older age,
      diabetes mellitus, lower serum cholesterol and lower serum triglyceride were
      independent risk factors for mortality. Further investigation is needed to
      clarify the prognostic impact of MetS in older adults.

PMID- 22659990
TI  - Serum ferritin and nutritional status in older adults at eldercare facilities.
AB  - OBJECTIVES: To identify serum ferritin levels and their association with
      nutritional status determined by Body Mass Index in older adults at four
      eldercare facilities. METHODS: An exploratory, cross-sectional study was carried
      out on 100 older adults residing at eldercare facilities in Colima, Mexico.
      Association between blood serum ferritin levels and nutritional status determined
      by Body Mass Index was evaluated. Ferritin levels were determined by means of
      chemiluminescence of blood samples obtained from subjects under control
      conditions. Descriptive statistics were used to analyze demographic
      characteristics. Student's t test and chi-square test were used to compare
      ferritin levels and Body Mass Index, respectively, between sexes. Statistical
      significance was considered to exist when P<= 0.05. Pearson's correlation was
      used to establish the relation between Body Mass Index and serum ferritin levels.
      RESULTS: Mean serum ferritin levels were 59.9489 ng/mL in women and 86.9266 ng/mL
      in men (P= 0.12). In regard to Body Mass Index there was statistical significance
      between normal vs overweight/obesity (P = 0.008), but not between normal vs
      underweight (P = 0.34). Body Mass Index/serum ferritin correlation was not
      statistically significant (Pearson's r = 0.003). CONCLUSIONS: The quantification
      of a single serum indicator is insufficient for determining nutritional status in
      the older adult.

PMID- 22659991
TI  - Osteoporosis among Italian women at risk: the OSTEOLAB study.
AB  - OBJECTIVE: The aim of the present study was to identify women at high risk of
      having osteoporosis according to the clinical judgment of their General
      Practitioners, but without a previous diagnosis of osteoporosis. DESIGN: Cross
      sectional survey. PARTICIPANTS: The General Practitioners were asked to select a
      sample of women aged 65 years or more who could be affected by osteoporosis but
      had never been diagnosed nor treated: this sample included 8,268. Moreover, 8,956
      women asked to be included in the study on a voluntary basis, and were analyzed
      separately. MEASUREMENTS: Participants were referred to a mobile unit equipped
      with GE Lunar Express Ultras (Achilles), where they were administered a
      questionnaire and underwent a QUS examination. They were classified at high,
      moderate or low risk of having osteoporosis according to the 2007 International
      Society for Clinical Densitometry official position. RESULTS: The prevalence rate
      of women at high risk of having osteoporosis was 12.5%; 53% were considered at
      moderate risk. Logistic regressions revealed that age, early age at menopause,
      history of fractures, dysthyroidism and smoking were associated with high and
      moderate risk. CONCLUSIONS: Results suggest that General Practitioners are able
      to identify women at risk of having osteoporosis, but often do not treat them,
      suggesting that osteoporosis in Italy is still a neglected condition. The
      strength of the association of risk factors is similar in women at high and
      medium risk: this may raise a debate on the validity of this classification in
      the Italian population.

PMID- 22659992
TI  - Comparison of skeletal muscle mass to fat-free mass ratios among different ethnic
      groups.
AB  - BACKGROUND: Asians seem to have less skeletal muscle mass (SMM) than other ethnic
      groups, but it is not clear whether relative SMM, i.e., SMM / height square or
      SMM to fat-free mass (FFM) ratio, differs among different ethnic groups at the
      same level of body mass index (BMI). OBJECTIVE: To compare the SMM to fat-free
      mass (FFM) ratio as well as anthropometric variables and body composition among 3
      ethnic groups. DESIGN, SETTING, AND PARTICIPANTS: Three hundred thirty-nine
      Japanese, 343 Brazilian, and 183 German men and women were recruited for this
      cross-sectional study. MEASUREMENTS: Muscle thickness (MTH) and subcutaneous fat
      thickness (FTH) were measured by ultrasound at nine sites on the anterior and
      posterior aspects of the body. FTH was used to estimate the body density, from
      which fat mass and fat-free mass (FFM) was calculated by using Brozek equation.
      Total SMM was estimated from ultrasound-derived prediction equations. RESULTS:
      Percentage body fat was similar among the ethnic groups in men, while Brazilians
      were higher than Japanese in women. In German men and women, absolute SMM and FFM
      were higher than in their Japanese and Brazilians counterparts. SMM index and
      SMM:FFM ratios were similar among the ethnic groups in women, excluding SMM:FFM
      ratio in Brazilian. In men, however, these relative values (SMM index and SMM:FFM
      ratio) were still higher in Germans. After adjusting for age and BMI, the SMM
      index and SMM:FFM ratios were lower in Brazilian men and women compared with the
      other two ethnic groups, while the SMM index and SMM:FFM ratios were similar in
      Japanese and German men and women, excluding SMM:FFM ratio in women. CONCLUSION:
      Our results suggest that relative SMM is not lower in Asian populations compared
      with European populations after adjusted by age and BMI.

PMID- 22659993
TI  - Interaction of physical activity level and metabolic syndrome among the adult
      Asian Indians living in Calcutta, India.
AB  - OBJECTIVES: The present community-based cross-sectional study was aimed to study
      the interaction of physical activity level (PAL) and metabolic syndrome (MS)
      among the adult Asian Indians. METHODS: A total of 448 adult (> 30 years)
      individuals (males and females) inhabiting in and around Calcutta, India
      participated in the study. Anthropometric measures, blood pressure, metabolic
      profiles and intake of dietary fatty acids were obtained from participants using
      standard guidelines. Metabolic syndrome (MS) was defined accordingly. The dietary
      intake (gram/week) of fatty acids namely total fat (TFA); saturated fatty acids
      (SFA); monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA)
      were obtained using nutritive values of Indian foodstuffs. Physical activity
      level (PAL) was categorized in to three different level: 1) high PAL - who
      exercised regularly and had physically demanding occupation 2) moderate PAL - who
      either exercised regularly or had physically demanding occupation, and 3) low PAL
      - who neither exercised regularly nor had physically demanding occupation.
      RESULTS: The prevalence of MS was found to be inversely related with PAL.
      Individuals with low PAL had higher prevalence of MS as compared to their
      counterparts. Moreover individuals with low PAL had significantly higher BMI, WC,
      WHR as well as TFA and SFA than individuals with moderate and high PAL.
      CONCLUSION: PAL is playing a vital role in the constellation of risk factors
      associated with MS. Habitual physical activity may be beneficial to prevent
      growing incidence of MS phenotypes in people of Asian Indian origin.

PMID- 22659994
TI  - A combination of galantamine and memantine modifies cognitive function in
      subjects with amnestic MCI.
AB  - OBJECTIVES: Mild cognitive impairment (MCI) is etiologically heterogeneous, and a
      substantial proportion of MCI subjects will develop different dementia disorders.
      One subtype of this syndrome, amnestic MCI, occurs preferentially but not
      exclusively in prodromal AD and is characterized by defined deficits of episodic
      memory. DESIGN, SETTING AND PARTICIPANTS: For a 2-year, double-blinded, placebo
      controlled study MCI patients, presenting with an amnestic syndrome but not
      necessarily based on presumed prodromal AD were randomized. INTERVENTION:
      Patients received (a) a combination of 16 mg galantamine plus 20 mg memantine, or
      (b) 16 mg galantamine alone or (c) placebo. MEASUREMENTS: The primary objective
      was to explore the differential impact of these interventions on the progression
      to dementia and on cognitive changes as measured by the ADAScog. RESULTS: After
      recruitment of 232 subjects, the trial was halted before reaching the planned
      sample size, because safety concerns arose in other studies with galantamine in
      MCI. This resulted in a variable treatment duration of 2-52 weeks. The
      statistical analysis plan was amended for studying cognitive effects of
      discontinuing the study medication, which was done separately for galantamine and
      memantine, and under double-blind conditions. There was one death, no unexpected
      severe adverse events, and no differences of severe adverse events between the
      treatment arms. The cognitive changes on the ADAScog were not different among the
      groups. Only for the subgroup of amnestic MCI with presumed AD etiology, a
      significant improvement of ADAScog score over placebo before the discontinuation
      of medication was observed, while amnestic MCI presumably due to other etiologies
      showed no cognitive changes with broad variation. Cognitive improvement was
      numerically larger in the combination treatment group than under galantamine
      alone. Patients who received placebo declined as expected. Discontinuation of
      galantamine, either as part of the combination regimen or as mono treatment,
      resulted in a transient decline of the ADAScog score in amnestic MCI of presumed
      AD etiology, while discontinuation of Memantine did not change the cognitive
      status. CONCLUSION: In an interrupted trial with amnestic MCI subjects the
      combination of galantamine plus memantine were generally well tolerated. In the
      subgroup of MCI subjects with presumed AD etiology, a cognitive benefit of a
      short-term combination treatment of galantamine plus memantine was observed, and
      cognitive decline occurred after discontinuation of galantamine.

PMID- 22659995
TI  - Lower intake of vegetables and legumes associated with cognitive decline among
      illiterate elderly Chinese: a 3-year cohort study.
AB  - BACKGROUND: Despite many studies on cognitive function and its influential
      factors among old population, relatively little research has been designed to
      study the relationship between dietary intake and cognitive function in elderly.
      OBJECTIVE: We conducted a population-based, prospective nested case-control study
      to investigate the association between dietary habits and declines in cognitive
      function over three years among Chinese illiterate elderly. DESIGN AND METHODS:
      This study was part of the Chinese Longitudinal Health Longevity Study (CLHLS).
      Six thousand nine hundred and eleven illiterate residents aged 65 or older were
      investigated. Socio-demographic and dietary habits data were collected at
      baseline. The cognitive function of illiterate elderly persons was assessed using
      Chinese revised Mini Mental State Examination (MMSE-r) in 2002 and 2005.
      Cognitive decline was defined as MMSE-r score dropped to less than 18 at follow
      up among those with normal cognitive function (MMSE-r>=18 at baseline). Odds
      ratios (OR) were calculated via logistic regression models. RESULTS: Five
      thousand six hundred and ninety one elderly were included in the current
      analysis. In bivariate analysis, cognitive decline was associated with gender,
      marital status ,financial status, smoking, drinking alcohol, drinking tea, eating
      fruits, vegetables, legumes, fishes, meat, egg and sugar. Multivariate logistic
      regression analysis found that always eating vegetable (Adjusted OR: 0.66; 95%
      confidence intervals, CI: 0.58, 0.75), always consuming legumes (AOR:0.78; 95%
      CI: 0.64, 0.96) were inversely associated with cognitive decline. CONCLUSIONS:
      Lower intakes of vegetables and legumes were associated with cognitive decline
      among illiterate elderly Chinese. Dietary factors may be important for prevention
      cognitive decline.

PMID- 22659996
TI  - Nutritional predictors of cognitive impairment severity in demented elderly
      patients: the key role of BMI.
AB  - INTRODUCTION: The body mass index (BMI) is commonly used to assess nutritional
      status and the Mini Mental State Examination (MMSE) is a validated tool for
      assessing cognitive status in elderly people. Nutritional and cognitive aspects
      are closely related in dementia. OBJECTIVES: To establish whether BMI predicts
      cognitive decline in demented patients and whether an "alarm" BMI cut-off exists
      for declining MMSE scores. SUBJECTS AND METHODS: 82 elderly demented patients
      underwent clinical, bio-chemical and functional assessment. DESIGN: Transversal
      study. RESULTS: The mean BMI was 26.08+/-4.48 kg/m2 and the mean MMSE 18.68+/
      5.38. Patients with BMI<25 kg/m2 had significantly lower MMSE scores (16.5+/-5.53
      vs 20.38+/-4.64; p 0.001), fat-free mass (FFM; 27.76+/-8.99 vs 37.38+/-10.58 kg;
      p<0.001), fat-free mass index (FFMI; 11.52+/-3.03 vs 14.67+/-2.89 kg/m2;
      p<0.001), and fat mass (FM; 24.90+/-6.89 vs 36.86+/-6.77 kg; p<0.001), as well as
      lower Mini Nutritional Assessment (MNA) scores (23.80+/-2.50 vs 25.00+/-2.29;
      p=0.03) and higher vitamin B12 levels (460.95+/-289.80 vs 332.43+/-82.07 pg/ml;
      p=0.01). In the sample as a whole, MMSE scores significantly correlated with
      scores for MNA (r=0.27, p=0.01), FFM (r=0.27, p=0.01), BMI (r=0.19, p=0.05), ADL
      (r=0.28, p=0.01) and instrumental activities of daily living (IADL; r=0.34,
      p=0.002). On multiple logistic regression, BMI<25 kg/m2 was independently
      associated with the risk of moderate-severe cognitive impairment (OR=2.96; 95%
      CI; 1.16-7.55) and female gender was independently associated with severity of
      dementia (OR=3.14; 95% CI; 1.09-9.03). CONCLUSION: BMI seems to indicate global
      health status in elderly demented people and a BMI of 25 kg/m2 can be considered
      an "alarm" cut-off, lower values coinciding with a worse cognitive status based
      on MMSE scores.

PMID- 22659997
TI  - Are atypical antipsychotics safer than typical antipsychotics for treating
      behavioral and psychological symptoms of dementia?
AB  - Atypical antipsychotics seem to be preferable than conventional agents in
      treating psychological symptoms of dementia (BPSD), because they have
      substantially lower risks of extrapyramidal neurological effects with lower
      reported rates of parkinsonism and tardive dyskinesia. However, in the course of
      time, with the increase in their use, more and more side effects have been
      reported.  The benefits and risks of antipsychotic treatment should be carefully
      evaluated according to the co-morbidity and the severity of the psychological and
      behavioral symptoms and their impact on the individual elderly patient. It is
      recommended to keep those medications in the lower range of therapeutic doses.
      Due to the complexity of the individual patient, no guidelines have been yet
      established. Therefore, clinical judgment should be used in applying the dose and
      the type of those drugs.

PMID- 22659998
TI  - Malnutrition screening and early nutrition intervention in hospitalised patients
      in acute aged care: a randomised controlled trial.
AB  - OBJECTIVES: High rates of malnutrition have been reported in the older
      hospitalized patient population. This is recognised to impact on patient outcomes
      and health costs. This study aimed to assess the impact of nutrition screening
      and intervention on these parameters. DESIGN: Randomised controlled prospective
      study. SETTING: The study was performed in the acute geriatric medicine wards of
      the Prince of Wales Hospital, Sydney Australia. PARTICIPANTS: All patients
      admitted to these wards under a geriatrician with an expected length of stay of
      at least 72 hours were considered for the study. INTERVENTION: Patients were
      screened on admission for malnutrition using the Mini Nutritional Assessment
      (MNA) tool and randomly assigned to control or intervention groups. Intervention
      patients were immediately commenced on a malnutrition care plan (MCP). Control
      patients were only commenced on a MCP if referred by clinical staff.
      MEASUREMENTS: Length of stay (LOS), weight change and frequency of readmission to
      hospital were compared between the groups. RESULTS: 143 patients were screened.
      119 were identified as malnourished (MN) or at risk of malnutrition (AR). Overall
      LOS was not different between the two groups (control v. intervention: 13.4 +/-
      1.3 days v. 12.5 +/- 1.2 days, p=0.64). However there was a significant decrease
      in LOS in the MN (control v. intervention: 19.5 +/- 3 days v. 10.6 +/- 1.6 days,
      p=0.013) and a trend to reduced readmissions. There was no difference in weight
      change over admission between the groups. Without screening, clinical staff
      identified only a small proportion of malnourished patients (35% of MN and 20% of
      AR). CONCLUSIONS: Malnutrition in the older hospital population is common.
      Malnutrition screening on hospital admission facilitated targeted nutrition
      intervention, however length of stay and re-presentations were only reduced in
      older malnourished patients with an MNA score less than 17.

PMID- 22659999
TI  - Vitamin B-12 supplementation improves arterial function in vegetarians with
      subnormal vitamin B-12 status.
AB  - OBJECTIVE: Vegetarians are more vascular-healthy but those with subnormal vitamin
      B-12 status have impaired arterial endothelial function and increased intima
      media thickness. We aimed to study the impact of vitamin B-12 supplementation on
      these markers, in the vegetarians. DESIGN: Double-blind, placebo controlled,
      randomised crossover study. SETTING: Community dwelling vegetarians.
      PARTICIPANTS: Fifty healthy vegetarians (vegetarian diet for at least 6 years)
      were recruited. INTERVENTION: Vitamin B-12 (500 ug/day) or identical placebo were
      given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and
      then open label vitamin B-12 for additional 24 weeks (n=41). MEASUREMENT: Flow
      mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of
      carotid artery were measured by ultrasound. RESULTS: The mean age of the subjects
      was 45+/-9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B
      12 levels <150 pmol/l. Vitamin B-12 supplementation significantly increased serum
      vitamin B-12 levels (p<0.0001) and lowered plasma homocysteine (p<0.05). After
      vitamin B-12 supplementation but not placebo, significant improvement of brachial
      FMD (6.3+/-1.8% to 6.9+/-1.9%; p<0.0001) and in carotid IMT (0.69+/-0.09 mm to
      0.67+/-0.09 mm, p<0.05) were found, with further improvement in FMD (to 7.4+/
      1.7%; p<0.0001) and IMT (to 0.65+/-0.09 mm; p<0.001) after 24 weeks open label
      vitamin B-12. There were no significant changes in blood pressures or lipid
      profiles. On multivariate analysis, changes in B-12 (beta=0.25; p=0.02) but not
      homocysteine were related to changes in FMD, (R=0.32; F value=3.19; p=0.028).
      CONCLUSIONS: Vitamin B-12 supplementation improved arterial function in
      vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for
      atherosclerosis prevention.

PMID- 22660000
TI  - Xerostomia and medication: a cross-sectional study in long-term geriatric wards.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of
      xerostomia in old people living in long-term geriatric wards, and to measure the
      relationship between xerostomia and etiologic factors such as age and medication
      (total number of medications, xerogenic medications, anticholinergic medications
      and medications that induce hypersialorrhea). DESIGN: An observational
      retrospective, comparative, multicentre epidemiological study. SETTING: Long-term
      geriatric wards, in Reims, France. PARTICIPANTS: 769 old people living in long
      term geriatric wards. MEASUREMENTS: Prevalence of xerostomia assessed from age,
      total number of medications, xerogenic medications, anticholinergic medications
      and those that induce hypersialorrhea. Multivariable logistic regression was used
      to calculate Odds Ratios (OR) and their 95% Confidence Intervals (95% CI).
      RESULTS: Among 769 old people (average age 84.6+/-8.4 years old), 287 residents
      suffered from xerostomia (37.3%). Significant predictors of xerostomia were:
      resident's age OR=1.56, 95% CI (1.30-1.88), p<0.0001 and anticholinergic
      medications OR=1.35, 95% CI (1.05-1.73), p=0.02. The only protective factor
      against xerostomia identified was medications that induce hypersialorrhea
      OR=0.81, 95% CI (0.67-0.98), p=0.03. The total number of medications and
      xerogenic medications did not play a significant role in xerostomia. CONCLUSION:
      Increasing Age and anticholinergic medications induce a dry mouth. Conversely,
      the total number of medications and xerogenic medications do not influence
      xerostomia. Medications that induce hypersialorrhea protect against the
      occurrence of dry mouth.

PMID- 22660001
TI  - The aging perioral region -- Do we really know what is happening?
AB  - OBJECTIVES: The perioral region is subject to a myriad of different treatments
      for rejuvenation, many of which are applied without a clear understanding of the
      underlying physiological processes of perioral aging. The results of these
      procedures are therefore sometimes not optimal and do not achieve a natural
      youthful appearance. The aim of this study was to put the results of three
      investigations into the perioral aging process into relation to clinical
      application in aesthetic medicine. DESIGN: Three different investigations were
      performed to evaluate the complex 3-dimensional changes during the perioral aging
      process. Perioral proportions of 182 standardized subject photographs were
      measured in a photomorphometric study and correlated to age. In cranial MRI scans
      of 30 women aged 20-35 and 30 women aged 65-80 relevant anatomical dimensions
      were measured. Histological cross cuts of the upper lip complex of 20 individuals
      in two age groups, young (< 40 years, n = 10) and old (> 80 years, n = 10), were
      analysed. The results were then set into relation to today's lip rejuvenation
      procedures. RESULTS: All studies showed a statistically significant lengthening
      of the aging upper lip. The photomorphometric study further showed an increase of
      prolabium skin at the cost of a decreasing visible upper lip vermilion. The MRI
      scans showed a decrease in thickness and redistribution towards a length increase
      but no total volume loss. Histomorphometric analysis revealed statistically
      significant thinning of the cutis, thickening of the subcutis and a degeneration
      of elastic and collagen fibers. The orbicularis oris muscle becomes thinner and
      shows a decrease of the forward curve defining the vermilion border. The results
      show that the main processes of lip aging are redistribution from thickness to
      length without total volume loss and a decrease of structural components of the
      lip, which leads to the decrease of pouting, an inversion of the vermilion and a
      ptosis of the lip. CONCLUSION: A new and better understanding of the underlying
      physiological changes of perioral aging is essential and will lead to a better
      and more specific implementation of perioral rejuvenation procedures which will
      lead to more natural results.

PMID- 22660008
TI  - Quantification of "fuzzy" chemical concepts: a computational perspective.
AB  - Chemists recurrently utilize "fuzzy" chemical concepts (e.g. atomic charges, the
      chemical bond, strain, aromaticity, branching, etc.), which lack unique
      quantitative assessments but, nonetheless, are frequently employed as tools for
      understanding the intricacies of chemical behaviour. This tutorial review
      provides an overview of the computational schemes specifically developed to
      quantify four of the most commonly employed, yet debated, chemical concepts: the
      chemical bond, atomic charges, (hyper)conjugation, and molecular strain. The
      enhanced knowledge gained from these schemes not only helps in the depiction of
      molecules with unique properties, but also provides breadth to our fundamental
      understanding of chemistry. Nevertheless, the numerous existing methodologies
      often result in different interpretations that culminate in discrepancies.
      Through recent examples in the literature, guidelines are provided which
      illustrate the strengths and weaknesses of various schemes for each individual
      concept.

PMID- 22660003
TI  - Differences in weight gain in hypertensive and diabetic elderly patients primary
      care study.
AB  - BACKGROUND: Treatment and care of elderly patients with diabetes and hypertension
      means a hard task in primary care. Patients with these two components of
      metabolic syndrome are often overweight or obese. Although some parameters of
      metabolic syndrome are usually measured in a medical setting, checking body
      weight is usually done by the patients. AIM: The aim of this study is to analyse
      the patients' self-recorded data on weight and compare them according to
      hypertension and diabetes. PATIENTS AND METHODS: Five hundred and forty people
      (225 men and 315 women) between 60 and 75 years of age were eventually selected
      in primary care settings. Retrospective self-recorded data on recent weights and
      every decade since the age of 20, as well as the decade prior to diagnosis were
      collected. The data of patients with and without diabetes and/or hypertension
      were compared. RESULTS: The current mean body weight was significantly higher in
      all groups than at the age of 20. Compared with the control group, hypertensive
      men and women were approximately of the same weight in their twenties and, also,
      recently, but they gained more weight in the 4th and 5th decades of their life.
      Diabetics started at higher weights. The greatest weight gain was observed as
      follows: between 20-30 years and 30-40 years in men and women, respectively, as
      well as between 50-60 years of age and in the last decade prior to diagnosis in
      both genders. Weight gain in the control group was steady at a lower rate.
      CONCLUSIONS: Weight gain between 20-40 years of age could be an important factor
      in the aetiology of diabetes. Stable or at least limited weight gain may be a
      preventive factor. Considering the limitations of the study, further and decades
      long epidemiological evaluations are suggested in a larger study population.

PMID- 22660002
TI  - Psoriasis in patients older than 65 years. A comparative study with younger adult
      psoriatic patients.
AB  - OBJECTIVES: To examine the clinical characteristics of psoriasis, prevalence of
      comorbidities and quality of life in psoriasis patients older than 65 years and
      to compare them with younger adult psoriatic patients. DESIGN: Prospective
      observational study of prevalence. SETTING AND PARTICIPANTS: Patients older than
      18 years with diagnosis of psoriasis attended at the Dermatology Department of
      the University Hospital of A Coruna (Galicia, Spain). A total of 371 patients
      were included (218 males and 153 females) with ages ranging from 18 to 85 years,
      of whom 70 were older than 65 years. MEASUREMENTS: Demographic data, clinical
      characteristics and psoriasis treatment, history of hypertension, diabetes
      mellitus, smoking and alcohol consumption and quality of life impairment were
      registered. Body mass index, waist-hip ratio, left ventricular hypertrophy,
      average value of systolic and diastolic blood pressure, cholesterol,
      triglycerides and glucose blood levels were also measured. RESULTS: Patients
      older than 65 years have statistically significant higher prevalence of
      hypertension, left ventricular hypertrophy, waist-hip ratio, diabetes mellitus
      and raised blood glucose levels. There was also association between clinical
      severity of psoriasis and smoking and alcohol intake as well as between quality
      of life and type of psoriasis treatment. CONCLUSIONS: Psoriasis in patients older
      than 65 years represents a significant proportion of cases and its prevalence is
      expected to increase. Because these patients are more prone to suffer
      comorbidities and to develop adverse effects due to psoriasis treatment,
      attention to pharmacologic interactions and correction of cardiovascular risk
      factors and toxic habits should be especially taken in mind in this age group.

PMID- 22660025
TI  - Effect of parathyroidectomy on subclinical cardiovascular disease in mild primary
      hyperparathyroidism.
AB  - OBJECTIVE: We recently demonstrated that mild primary hyperparathyroidism (PHPT)
      is associated with increased carotid intima-media thickness (IMT) and stiffness,
      and increased aortic valve calcification. It is unclear whether parathyroidectomy
      (PTX) improves these abnormalities. The purpose of this study was to determine
      whether cardiovascular abnormalities in PHPT improve with PTX. DESIGN: Forty-four
      patients with PHPT were studied using carotid ultrasound and transthoracic
      echocardiography before and after PTX. Carotid IMT, carotid plaque and stiffness,
      left ventricular mass index (LVMI), myocardial and valvular calcification, and
      diastolic function were measured before, 1- and 2-year post-PTX. RESULTS: Two
      years after PTX, increased carotid stiffness tended to decline to the normal
      range (17%, P=0.056) while elevated carotid IMT did not improve. Carotid plaque
      number and thickness, LVMI and cardiac calcifications did not change after PTX,
      while some measures of diastolic function (isovolumic relaxation time (IVRT) and
      tissue Doppler peak early diastolic velocity) worsened within the normal range.
      Indices did improve in patients with cardiovascular abnormalities at baseline.
      Increased carotid stiffness improved by 28% (P=0.004), a decline likely to be of
      clinical significance. More limited improvements also occurred in elevated IMT
      (3%, P=0.017) and abnormal IVRT (13%, P<0.05), a measure of diastolic
      dysfunction. CONCLUSIONS: In mild PHPT, PTX led to modest changes in some
      cardiovascular indices. Improvements were mainly evident in those with
      preexisting cardiovascular abnormalities, particularly elevated carotid
      stiffness. These findings are reassuring with regard to current international
      guidelines that do not include cardiovascular disease as a criterion for PTX.

PMID- 22660026
TI  - Comparison of a soluble co-formulation of insulin degludec/insulin aspart vs
      biphasic insulin aspart 30 in type 2 diabetes: a randomised trial.
AB  - OBJECTIVE: Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation
      of insulin degludec (70%) and insulin aspart (IAsp: 30%). Here, we compare the
      efficacy and safety of IDegAsp, an alternative IDegAsp formulation (AF:
      containing 45% IAsp), and biphasic IAsp 30 (BIAsp 30). DESIGN: Sixteen-week, open
      label, randomised, treat-to-target trial. METHODS: Insulin-naive subjects with
      type 2 diabetes (18-75 years) and a HbA1c of 7-11% were randomised to twice-daily
      IDegAsp (n=61), AF (n=59) or BIAsp 30 (n=62), all in combination with metformin.
      Insulin was administered pre-breakfast and dinner (main evening meal) and
      titrated to pre-breakfast and pre-dinner plasma glucose (PG) targets of 4.0-6.0
      mmol/l. RESULTS: Mean HbA1c after 16 weeks was comparable for IDegAsp, AF and
      BIAsp 30 (6.7, 6.6 and 6.7% respectively). With IDegAsp, 67% of subjects achieved
      HbA1c 7.0% Without confirmed hypoglycaemia in the last 4 weeks of treatment
      compared with 53% (AF) and 40% (BIAsp 30). Mean fasting PG was significantly
      lower for IDegAsp vs BIAsp 30 (treatment difference (TD): -0.99 mmol/l (95%
      confidence interval: -1.68; 0.29)) and AF vs BIAsp 30 (TD: -0.88 mmol/l (-1.58; 
      0.18)). A significant, 58% lower rate of confirmed hypoglycaemia was found for
      IDegAsp vs BIAsp 30 (rate ratio (RR): 0.42 (0.23; 0.75)); rates were similar for
      AF vs BIAsp 30 (RR: 0.92 (0.54; 1.57)). IDegAsp and AF had numerically lower
      rates of nocturnal confirmed hypoglycaemia vs BIAsp 30 (RR: 0.33 (0.09; 1.14) and
      0.66 (0.22; 1.93) respectively). CONCLUSIONS: IDegAsp provided comparable overall
      glycaemic control to BIAsp 30 with a significantly lower rate of hypoglycaemia.

PMID- 22660028
TI  - Fourier transform-based iterative method for differential phase-contrast computed
      tomography.
AB  - In this Letter, a novel Fourier transform-based iterative method is proposed to
      reconstruct a refractive index distribution in an object directly from measured
      differential phase shifts. This reconstruction method offers distinct advantages
      over the analytic method in cases of noisy and/or few-view data, since the
      iterative scheme can easily incorporate compressive sensing and maximum
      likelihood techniques to achieve high image quality. Numerical simulation and
      biological sample experiments demonstrate the merits of the proposed approach.

PMID- 22660027
TI  - Flexible optitrode for localized light delivery and electrical recording.
AB  - We present optitrode, a miniaturized flexible probe for integrated, localized
      light delivery and electrical recording. This device features an annular light
      guide with transparent polymer and fused silica layers surrounding a twisted-wire
      tetrode. We have developed a novel fabrication process, V-groove guided capillary
      assembly, to achieve high-precision, coaxial alignment of the various layers of
      the device. Optitrode with a length-to-diameter ratio ~500 (5 cm long, 100 MUm
      diameter) has been fabricated, and both the electrical and optical functions have
      been characterized. The prototype can deliver 11% (110 mW) of the total laser
      power under abrupt bending angle ~25 degrees .

PMID- 22660029
TI  - Generation of tunable octave-spanning mid-infrared pulses by filamentation in gas
      media.
AB  - The continued development of femtosecond mid-infrared (IR) sources with
      ultrabroad spectral width is critical for probing and controlling complex
      molecular structural dynamics on an ultrafast timescale. We report on a sub-20
      fs, coherent mid-IR source with an octave-spanning spectral bandwidth (>2000 cm(
      1)) tunable from 2-8 micrometers (37.5-150 THz), with energy >0.4 MUJ/pulse at 1
      kHz. The mid-IR pulses are generated by four-wave mixing during the filamentation
      of intense 800 nm and 400 nm pulses in various gas media. Spectral tunability is
      achieved by the choice of gas, pressure and input 800 nm pulse energy.

PMID- 22660030
TI  - Young's two-slit interference of vector light fields.
AB  - We explore the peculiar interference behaviors of the vector fields in the
      Young's two-slit configuration. The interference patterns have a chessboard
      structure in the middle region and depend on the topological charge and the
      initial phase of the input vector field. The results have potential applications
      such as characterizing the topological properties of the arbitrary vector fields.

PMID- 22660031
TI  - Pulse propagation of photon-added coherent states in waveguides with side-coupled
      nonlinear cavities.
AB  - We present a theoretical analysis of pulse propagation in a waveguide with a side
      coupled Kerr nonlinear cavity. As a specific application, we demonstrate how the
      nonlinearity has a profound influence on transport properties of a photon-added
      coherent state. We find that the fields provided by the coherent states
      facilitate a tunable nonlinearity on the few-photon level, allowing for a robust
      gating of single photons.

PMID- 22660032
TI  - Highly flexible and efficient top-emitting organic light-emitting devices with
      ultrasmooth Ag anode.
AB  - We demonstrate highly flexible and efficient top-emitting organic light-emitting
      devices (TOLEDs) by using an ultrasmooth Ag anode. A template-stripping process
      has been employed to create the ultrasmooth Ag anode on a photopolymer substrate.
      The flexible TOLEDs obtained by this method keep good electroluminescence
      properties under a small bending radius and after repeated bending. The
      efficiency of the flexible TOLEDs is improved by 60% compared with the
      conventional TOLEDs deposited on Si substrate due to the enhanced hole injection
      from the ultrasmooth anode.

PMID- 22660033
TI  - Stable bright and vortex solitons in photonic crystal fibers with inhomogeneous
      defocusing nonlinearity.
AB  - We predict that a photonic crystal fiber whose strands are filled with a
      defocusing nonlinear medium can support stable bright solitons and also vortex
      solitons if the strength of the defocusing nonlinearity grows toward the
      periphery of the fiber. The domains of soliton existence depend on the transverse
      growth rate of the filling nonlinearity and nonlinearity of the core. Remarkably,
      solitons exist even when the core material is linear.

PMID- 22660034
TI  - Polarization-dependent refractometer for discrimination of temperature and
      ambient refractive index.
AB  - Transmission characteristics of polarization-dependent refractometer based on a
      surface long-period grating (SLPG) inscribed in a D-shaped photonic crystal fiber
      (PCF) are investigated. The birefringence of SLPG produces the separation of
      transmission spectra for TE and TM polarization modes. We also measure the
      sensitivities of PCF-based SLPG to temperature and external refractive index
      change depending on the input polarization states. The SLPG-based sensor exhibits
      different temperature and ambient index sensitivities corresponding to TE and TM
      polarization modes. Therefore, the SLPG inscribed in D-shaped PCFs can
      effectively discriminate temperature and ambient index sensitivities.

PMID- 22660035
TI  - Quantitative pupil analysis in stimulated emission depletion microscopy using
      phase retrieval.
AB  - The resolution attainable with stimulated emission depletion (STED) microscopy
      greatly depends on the quality of the STED laser focus. So far, visual inspection
      of a measured STED focus has been the only convenient means of gauging the source
      of aberrations. Here we describe a method, requiring no instrument modifications,
      for obtaining an equivalent to the complex pupil function at the back aperture of
      the objective and show that it provides quantitative information about aberration
      sources (including aberrations induced by the objective or sample). We show the
      accuracy of this field representation to be sufficient for reconstructing the
      STED focus in three dimensions and determining corrective steps.

PMID- 22660036
TI  - Optimized annular phase masks to extend depth of field.
AB  - A radially symmetric phase mask composed of several annular zones with equal area
      (called APM) was designed based on the incoherent imaging theory from Fourier
      Optics. The phase of any ring equals minus of the phase function caused by
      certain defocus. Another circularly symmetric phase mask similar to the APM
      (called MQPM) was proposed, except for the different phase function deriving from
      the quartic phase mask (QPM). For MQPM, there are two differences from an
      existing phase mask: the selection of the phase parameters and the method to
      divide the phase mask. An optimization model was developed to obtain optimized
      parameters of the phase masks. Numerical evaluations show that both APM and MQPM
      are less insensitive to defocus than QPM, and the defocused optical transfer
      functions with two phase masks are symmetric about the in-focus plane in the
      axial direction.

PMID- 22660037
TI  - Improved measurement of polarization state in terahertz polarization
      spectroscopy.
AB  - A calibration scheme is presented for improved polarization state measurement of
      terahertz pulses. In this scheme the polarization response of a two-contact
      terahertz photoconductive detector is accurately measured, and is used to correct
      for the impact of the nonidealities of the detector. Experimental results show
      excellent subdegree angular accuracy and at least 60% error reduction with this
      scheme.

PMID- 22660038
TI  - Bipolar resistance effect observed in CdSe quantum-dots dominated structure of
      Zn/CdSe/Si.
AB  - In this study, we report our new finding of bipolar resistance effect (BRE) in
      quantum dots (QDs)-embedded structure of Zn/CdSe/Si. This effect features a
      remarkable linear resistance change and an enhanced BRE when a laser moves along
      the surface of the structure. The results show that the combination of BRE with
      QDs is useful for applications and may add a new functionality to QDs-based
      optoelectronic devices.

PMID- 22660039
TI  - A spectrally constrained dual-band normalization technique for protoporphyrin IX
      quantification in fluorescence-guided surgery.
AB  - We report a dual-band normalization technique for in vivo quantification of the
      metabolic biomarker, protoporphyrin IX (PpIX), during brain tumor resection
      procedures. The accuracy of the approach was optimized in tissue simulating
      phantoms with varying absorption and scattering properties, validated with
      fluorimetric assessments on ex vivo brain tissue, and tested on human data
      acquired in vivo during fluorescence-guided surgery of brain tumors. The results
      demonstrate that the dual-band normalization technique allows PpIX concentrations
      to be accurately quantified by correction with reflectance data recorded and
      integrated within only two narrow wavelength intervals. The simplicity of the
      method lends itself to the enticing prospect that the method could be applicable
      to wide-field applications in quantitative fluorescence imaging and dosimetry in
      photodynamic therapy.

PMID- 22660040
TI  - Plasmonic quarter-wave plate.
AB  - Here we present a strategy for designing wave plates utilizing resonances of
      subwavelength apertures in metallic films. Specifically, we show that it is
      possible to tune the geometry in a periodic array of cross-shaped apertures in a
      silver film to produce a quarter-wave plate at a particular wavelength in the
      near-infrared. This is achieved by introducing an asymmetry into the lengths of
      the arms of the crosses.

PMID- 22660041
TI  - Linearized analog photonic links based on a dual-parallel polarization modulator.
AB  - A linearized analog photonic link (APL) is proposed based on an integratable
      electro-optic dual-parallel polarization modulator (DPPolM), which consists of
      two polarization beam splitters and two polarization modulators (PolMs).
      Theoretical analysis shows that the APL is potentially free from the third-order
      nonlinear distortion if a polarization controller placed before the DPPolM is
      carefully adjusted. A proof-of-concept experiment is carried out. A reduction of
      the third-order intermodulation components as high as 40 dB and an improvement of
      the spurious-free dynamic range as large as 15.5 dB is achieved as compared with
      a single PolM-based link. The DPPolM-based APL is simple, compact, and power
      efficient since it requires only one laser, one modulator, and one photodetector.

PMID- 22660042
TI  - High peak power optical pulses generated with a monolithic master-oscillator
      power amplifier.
AB  - We present results on a monolithic semiconductor-based master-oscillator power
      amplifier (MOPA) combining a distributed-feedback (DFB) laser and a tapered
      amplifier on a single chip. The MOPA reaches an output power of almost 12 W at an
      emission wavelength around 1064 nm in continuous-wave operation. Pulses with a
      length of around 100 ps can be obtained either by injecting nanosecond current
      pulses into the tapered amplifier alone or into both the DFB laser and the
      tapered amplifier. In the latter case, pulses with a width of 84 ps, a peak power
      of 42 W, and a spectral width of 160 pm are generated.

PMID- 22660043
TI  - Dual-negative-refraction and imaging effects in normal two-dimensional photonic
      crystals with hexagonal lattices.
AB  - A novel dual-negative-refraction (DNR) effect is studied in two types of normal
      two-dimensional photonic crystals (2DPCs) with hexagonal lattices. Systematical
      analyses of the band structures and equifrequency surfaces indicate that the DNR
      may be realized when the overlapping second and third bands with relatively flat
      shapes and only a slight separation are available at some frequencies close to
      the band's peak of 2DPCs. Further simulations have not only confirmed the DNR and
      corresponding dual-imaging effects in normal 2DPCs with hexagonal lattices but
      also revealed some relative rules to the dual images. In particular, the
      thickness as well the cutoff value at terminations of PCs can strongly influence
      the performance of dual images and even determine whether the dual images would
      appear. Moreover, a relatively low working frequency is recommended to minimize
      the distortion degree of dual images.

PMID- 22660044
TI  - Enhanced Cerenkov second-harmonic emission in nonlinear photonic structures.
AB  - We study experimentally and theoretically the Cerenkov-type second-harmonic
      generation in a one-dimensional nonlinear photonic crystal. We demonstrate that
      the power of emitted second-harmonic can be enhanced 270 times by varying the
      angle of incidence of the fundamental beam such that the reciprocal lattice
      vector of the crystal can be used to compensate for the phase mismatch in the
      transverse direction enabling interaction in the nonlinear Bragg diffraction
      regime.

PMID- 22660045
TI  - Probing the photonic density of states using layer-by-layer self-assembly.
AB  - The process of spontaneous emission can be dramatically modified by optical
      microstructures and nanostructures. We have studied the modification of
      fluorescence dynamics using a variable thickness polymer spacer layer fabricated
      using layer-by-layer self-assembly with nanometer accuracy. The change in
      fluorescence lifetime with spacer layer thickness agrees well with theoretical
      predictions based on the modified photonic density of states (PDOS), and yields
      consistent values for the fluorophores' intrinsic fluorescence lifetime and
      quantum yield near a dielectric as well as a plasmonic interface. Based on this
      observation, we further demonstrate that self-assembled fluorophores can be used
      to probe the modified PDOS near optical microstructures and nanostructures.

PMID- 22660046
TI  - Quantification of the reduced scattering coefficient and phase-function-dependent
      parameter gamma of turbid media using multidiameter single fiber reflectance
      spectroscopy: experimental validation.
AB  - Multidiameter single fiber reflectance (MDSFR) spectroscopy is a method that
      allows the quantification of MUs' and the phase-function-dependent parameter
      gamma of a turbid medium by utilizing multiple fibers with different diameters.
      We have previously introduced the theory behind MDSFR and its limitations, and
      here we present an experimental validation of this method based on phantoms
      containing a fractal distribution of polystyrene spheres both in the absence and
      presence of the absorber Evans Blue.

PMID- 22660047
TI  - Fast photorefractive response of vanadium-doped lithium niobate in the visible
      region.
AB  - A series of vanadium-doped lithium niobate crystals was grown and their
      photorefractive properties were investigated with a 532 nm laser. At a total
      light intensity of 471 mW/cm(2), a short response time of only 0.57 s was
      achieved for 0.1 mol.% vanadium in LiNbO(3). The photorefractive process is
      dominated by the diffusion field instead of the photovoltaic field. The dominant
      charge carriers are electrons. The possible mechanism for the fast
      photorefractive response is discussed.

PMID- 22660048
TI  - Matching of the propagation constants in an asymmetric single-mode fused fiber
      coupler for core pumping thulium-doped fiber at 795 nm.
AB  - We developed a fused fiber coupler (FFC) capable of multiplexing wavelengths in
      the range of 795 nm and 2 MUm. A simple 2D simulation model to calculate the
      pretaper length for matching the propagation constants in the coupling region was
      established. Based on the numerical data, we fabricated an asymmetric FFC
      consisting of two different fibers with single-mode guidance for the respective
      wavelength, achieving a transmission of 90% in the signal fiber for both
      wavelengths. In order to demonstrate the application, we integrated the FFC into
      a core pumped thulium-doped fiber amplifier.

PMID- 22660049
TI  - Infrared cylindrical cloak in nanosphere dispersed liquid crystal metamaterial.
AB  - We present a design of an infrared cylindrical cloak using nanosphere dispersed
      nematic liquid crystal (NLC) metamaterial following the approach of Smith's group
      [Science 314, 977 (2006)]. Cloaking conditions require spatial distribution of
      liquid crystal birefringence with constant extraordinary index of refraction and
      radially dependent ordinary index of refraction. An approximate analytical
      formula for the latter is derived. Finite element (FE) simulations confirm the
      cloaking effect. Owing to the tunable birefringence of the liquid crystal
      component, such cloaking material offers the interesting possibilities of real
      time control of invisibility. The possibility of experimental realization is
      briefly discussed.

PMID- 22660050
TI  - Single-frequency, Q-switched Ho:YAG laser at room temperature injection-seeded by
      two F-P etalons-restricted Tm, Ho:YAG laser.
AB  - We demonstrated a 1.91 MUm pumped, injection-seeded Q-switched Ho:YAG laser
      operating at room temperature. By inserting two Fabry-Perot etalons into the
      laser cavity, single-frequency Tm, Ho:YAG seed lasing was achieved at a
      wavelength of 2090.9 nm, with a typical output power of 60 mW. Single-frequency,
      nearly transform-limited Q-switched operation of the Ho:YAG laser was achieved by
      injection seeding. The output energy of the single-frequency Q-switched pulse is
      7.6 mJ, with a pulse width of 132 ns and a repetition rate of 100 Hz. We measured
      the pulse spectrum, half-width of which was 3.5 MHz, by a heterodyne technique.

PMID- 22660051
TI  - Poly(styrene)-based graded-index plastic optical fiber for home networks.
AB  - We investigated poly(styrene) (PSt)-based graded-index plastic optical fiber (GI
      POF) with low loss and high bandwidth for home networks. To install the GI-POF in
      home networks, the attenuation must be below 200 dB/km at a 670-680 nm
      wavelength, and the bandwidth must be over 2.0 GHz for the 50 m fiber. In this
      study, we selected a dibenzothiophene (DBT) as a dopant to PSt, and we fabricated
      PSt-DBT-based GI-POF. We confirmed that the PSt-DBT-based GI-POF has high
      bandwidth (4.4 GHz) for 50 m fiber and low loss (166-193 dB/km) at a 670-680 nm
      wavelength and obtained the GI-POF that satisfied the requirements for home
      networks.

PMID- 22660052
TI  - Z-scan measurement of the nonlinear refractive index of graphene.
AB  - Under strong laser illumination, few-layer graphene exhibits both a transmittance
      increase due to saturable absorption and a nonlinear phase shift. Here, we
      unambiguously distinguish these two nonlinear optical effects and identify both
      real and imaginary parts of the complex nonlinear refractive index of graphene.
      We show that graphene possesses a giant nonlinear refractive index n(2)?10(-7)
      cm(2) W(-1), almost 9 orders of magnitude larger than bulk dielectrics. We find
      that the nonlinear refractive index decreases with increasing excitation flux but
      slower than the absorption. This suggests that graphene may be a very promising
      nonlinear medium, paving the way for graphene-based nonlinear photonics.

PMID- 22660053
TI  - 6.1 W single frequency laser output at 1645 nm from a resonantly pumped Er:YAG
      nonplanar ring oscillator.
AB  - A monolithic 1645 nm Er:YAG nonplanar ring oscillator (NPRO) resonantly pumped by
      a 1532 nm fiber laser is demonstrated. For reducing the energy-transfer
      upconversion effect, a 0.5% doped Er:YAG nonplanar crystal was used. An up to 6.1
      W single frequency laser output at 1645 nm was obtained, with a slope efficiency
      of 55.2% and an optical efficiency of 48.0%. The linewidth of the Er:YAG NPRO was
      14.4 kHz.

PMID- 22660054
TI  - Toward higher-order passive harmonic mode-locking of a soliton fiber laser.
AB  - We report >13 MHz/mW pump power efficiency in increasing the repetition rate of
      passive harmonic mode-locking by engineering the soliton pulse energy in Er fiber
      lasers incorporating carbon nanotube saturable absorber. Stable pulses with a ~5
      GHz repetition rate and 40 dB of super-mode suppression are demonstrated with
      only ~400 mW pump power in a single-clad fiber laser.

PMID- 22660055
TI  - Nonlinear localized modes in Glauber-Fock photonic lattices.
AB  - We study a nonlinear Glauber-Fock lattice and the conditions for the excitation
      of localized structures. We investigate the particular linear properties of these
      lattices, including linear localized modes. We investigate numerically nonlinear
      modes centered in each site of the lattice. We found a strong disagreement of the
      general tendency between the stationary and the dynamical excitation thresholds.
      We define a new parameter that takes into account the stationary and dynamical
      properties of localized excitations.

PMID- 22660057
TI  - Evolution of Airy beams in a chiral medium.
AB  - We study the evolution of Airy beams in chiral media. We numerically demonstrate
      that the circularly polarized Airy beams of opposite handedness can be separated
      when traveling through the chiral media. The constructive interference of the
      Airy beams in the near- and far-zone is explicitly analyzed by varying the
      chirality parameter of the medium. It is interesting to find that the self
      acceleration of the beam is sensitive to the interference term.

PMID- 22660056
TI  - Derivative method for phase retrieval in off-axis quantitative phase imaging.
AB  - We present a method for phase retrieval in off-axis interferometric systems. By
      numerically calculating the transverse 1st and 2nd order derivatives of the
      interferogram, we show that one can directly retrieve the quantitative phase
      image, without the need for Fourier or Hilbert transformations. Because of this,
      the method is significantly faster than the current approaches. We illustrate our
      method using biological specimen data from three different off-axis quantitative
      phase imaging techniques.

PMID- 22660058
TI  - Linear and nonlinear waves in surface and wedge index potentials.
AB  - We study optical beams that are supported at the surface of a medium with a
      linear index potential and by a piecewise linear wedge-type potential. In the
      linear limit the modes are described by Airy functions. In the nonlinear regime
      we find families of solutions that bifurcate from the linear modes and study
      their stability for both self-focusing and self-defocusing Kerr nonlinearity. The
      total power of such nonlinear waves is finite without the need for apodization.

PMID- 22660059
TI  - Enhancement of ultrafast nonlinear optical response of silicon nanocrystals by
      boron-doping.
AB  - Nonlinear optical responses of boron (B)-doped silicon nanocrystals (Si-ncs)
      embedded in borosilicate glass were studied by z-scan and optical Kerr gate
      methods under femtosecond excitation at 780 nm. The nonlinear refractive index
      (n(2)) and the two photon absorption coefficients (beta) of B-doped Si-ncs were
      found to be 3 times enhanced, compared to those of intrinsic Si-ncs. The response
      time was faster than 100 fs even at 5 K. The origin of the large nonlinear
      optical response was discussed, based on the experimental data of n(2), electron
      spin resonance spectra, and linear absorption spectra.

PMID- 22660060
TI  - Coherent synthesis of ultra-broadband optical parametric amplifiers.
AB  - We report on coherent synthesis of two ultra-broadband optical parametric
      amplifiers, each compressed by chirped mirror pairs, resulting in almost-octave
      spanning (520-1000 nm) spectra supporting nearly single-cycle sub-4 fs pulse
      duration. Synthesized pulse timing is locked to less than 30 as by a balanced
      optical cross-correlator. The synthesized pulse is characterized by two
      dimensional spectral interferometry and has a 3.8 fs duration.

PMID- 22660061
TI  - Simultaneous swept source optical coherence tomography of the anterior segment
      and retina using coherence revival.
AB  - We report on an implementation of coherence revival-based heterodyne swept source
      optical coherence tomography that is capable of simultaneously imaging the
      anterior and posterior eye. A polarization-encoded sample arm was used to
      efficiently focus orthogonal polarizations on the anterior segment and retina.
      Depth encoding was achieved using coherence revival, which allows for multiple
      depths within a sample to be simultaneously imaged and frequency encoded by
      carefully controlling the optical pathlength of each sample path. This design is
      a significant step toward whole-eye optical coherence tomography (OCT), which
      would enable customized ray-traced modeling of patient eyes to improve refractive
      surgical interventions and eliminate optical artifacts in retinal OCT
      diagnostics. We demonstrated the feasibility of this system for in vivo imaging
      by simultaneously acquiring images of the anterior segments and retinas in
      healthy human volunteers.

PMID- 22660062
TI  - Microelectromechanical systems bimaterial terahertz sensor with integrated
      metamaterial absorber.
AB  - This Letter describes the fabrication of a microelectromechanical systems (MEMS)
      bimaterial terahertz (THz) sensor operating at 3.8 THz. The incident THz
      radiation is absorbed by a metamaterial structure integrated with the bimaterial.
      The absorber was designed with a resonant frequency matching the quantum cascade
      laser illumination source while simultaneously providing structural support,
      desired thermomechanical properties and optical readout access. Measurement
      showed that the fabricated absorber has nearly 90% absorption at 3.8 THz. A
      responsivity of 0.1 degrees /MUW and a time constant of 14 ms were observed. The
      use of metamaterial absorbers allows for tuning the sensor response to the
      desired frequency to achieve high sensitivity for potential THz imaging
      applications.

PMID- 22660063
TI  - Octave-spanning supercontinuum generation of vortices in an As2S3 ring photonic
      crystal fiber.
AB  - We propose As(2)S(3) ring photonic crystal fiber (PCF) for supercontinuum
      generation of optical vortex modes. Due to the large material index contrast
      between As(2)S(3) and air holes in the designed ring PCF, there is a two-orders
      of-magnitude improvement of the difference between the effective refractive
      indices of different vortex modes compared with regular ring fiber. The design
      freedom of PCFs enables a low dispersion (<60 ps/nm/km variation in total) over a
      522 nm optical bandwidth. Moreover, the vortex mode has a large nonlinear
      coefficient of 11.7/W/m at 1550 nm with a small confinement loss of <0.03 dB/m up
      to 2000 nm. An octave-spanning supercontinuum spectrum of the vortex mode is
      generated from 1196 to 2418 nm at -20 dB by launching a 120 fs pulse with a 60 W
      peak power at 1710 nm into a 1 cm long As(2)S(3) ring PCF.

PMID- 22660064
TI  - Surface optical Bloch oscillations in semi-infinite waveguide arrays.
AB  - We predict that surface optical Bloch oscillations can exist in semi-infinite
      waveguide arrays with a linear index variation, if the array parameters close to
      the boundary are appropriately perturbed. The perturbation is such that the
      surface states obtain the Wannier-Stark ladder eigenvalues of the unperturbed
      infinite array. The number of waveguides, whose parameters need to be controlled,
      decreases with increasing ratio of index gradient over coupling. The
      configuration can find applications as a "matched" termination of waveguide
      arrays to eliminate the distortion of Bloch oscillations due to reflection on the
      boundaries.

PMID- 22660065
TI  - Broadly tunable one-way terahertz plasmonic waveguide based on nonreciprocal
      surface magneto plasmons.
AB  - One-way-propagating broadly tunable terahertz plasmonic waveguide at a
      subwavelength scale is proposed based on a metal-dielectric-semiconductor
      structure. Unlike other one-way plasmonic devices that are based on interference
      effects of surface plasmons, the proposed one-way device is based on
      nonreciprocal surface magneto plasmons under an external magnetic field.
      Theoretical and simulation results demonstrate that the one-way-propagating
      frequency band can be broadly tuned by the external magnetic fields. The proposed
      concept can be used to realize various high performance tunable plasmonic devices
      such as isolators, switches and splitters for ultracompact integrated plasmonic
      circuits.

PMID- 22660066
TI  - All-optical wavelength conversion and multicasting for polarization-multiplexed
      signal using angled pumps in a silicon waveguide.
AB  - We report all-optical wavelength conversion and multicasting for a 20 Gb/s (2*10
      Gb/s) polarization-multiplexed (Pol-MUX) nonreturn-to-zero amplitude-shift keying
      signal using four-wave mixing (FWM) in a silicon waveguide. The temporal
      waveforms and eye diagrams demodulated from both polarization channels of the
      converted idler are clearly observed. Moreover, the wavelength multicasting of
      the Pol-MUX signal is also demonstrated by using two incident pumps.

PMID- 22660067
TI  - Noise conversion from pump to the passively mode-locked fiber lasers at 1.5 MUm.
AB  - We characterize the noise conversion from the pump relative intensity noise (RIN)
      to the RIN and phase noise of passively mode-locked lasers at 1.5 MUm. Two mode
      locking mechanisms, nonlinear polarization rotation (NPR) and semiconductor
      saturable absorber mirror (SESAM), are compared for noise conversion for the
      first time. It is found that the RIN and the phase noise of both types of lasers
      are dominated by the noise converted from the pump RIN and thus, can be predicted
      with the measured pump RIN and noise conversion ratios. The SESAM laser is found
      to show an excess noise conversion from the laser RIN to the laser phase noise
      due to the slow saturable absorber effect.

PMID- 22660068
TI  - Multivariate empirical mode decomposition approach for adaptive denoising of
      fringe patterns.
AB  - An adaptive approach is presented for noise reduction of optical fringe patterns
      using multivariate empirical mode decomposition. Adjacent rows and columns of
      patterns are treated as multichannel signals and are decomposed into multiscale
      components. Fringe patterns are reconstructed with less noise by simply
      thresholding coefficients in different scales. The proposed approach can better
      concentrate local main components of fringe signals into single scale, compared
      with the conventional multiscale denoising method. A simulated pattern and an
      actual example are examined. Signal-to-noise ratio (SNR) of the simulated pattern
      is more than doubled.

PMID- 22660069
TI  - Broadband light source shearing interferometer using Savart plate and angular
      scanning technique.
AB  - A shearing interferometer based on using broadband light source, Savart plate,
      and angular scanning technique is proposed for slope contour measurements in this
      Letter. Of which, the Savart plate divides the wavefront reflected from the
      detected surface into two laterally displaced ones, the interference pattern
      generated by the interference of the divided wavefronts is modulated by an
      envelope function, and the slope contour of the detected surface is determined by
      examining the shifting of the darkest fringe as the shear plate is angularly
      scanned. A setup for realizing the interferometer is constructed. The
      experimental results of using this setup agree the validity and feasibility of
      the proposed interferometer.

PMID- 22660070
TI  - Broadband source of polarization entangled photons.
AB  - A broadband source of polarization entangled photons based on type-II spontaneous
      parametric down conversion from a chirped PPKTP crystal is presented. With
      numerical simulation and experimental evaluation, we report a source of broadband
      polarization entangled states with a bandwidth of approximately 125 nm for use in
      quantum interferometry. The technique has the potential to become a basis for the
      development of flexible broadband sources with designed spectral properties.

PMID- 22660071
TI  - Suppression of parasitic lasing in high energy, high repetition rate Ti:sapphire
      laser amplifiers.
AB  - Transverse parasitic lasing is well known for limiting the signal gain and the
      pulse energy that can be extracted from Ti:sapphire petawatt amplifiers. We have
      developed a technique for suppressing these parasitic lasing modes based on
      perfect refractive index-matching liquid doped with a broad-bandwidth absorber to
      suppress the transverse lasing while ensuring proper heat removal from the
      Ti:sapphire crystal. The 800 nm laser output with a bandwidth of 41 nm (FWHM) and
      peak energy of 22.7 J at a repetition rate of 1 Hz is demonstrated.

PMID- 22660072
TI  - Self-collimation of surface plasmon beams.
AB  - We generate self-collimating surface plasmon beams in a doubly periodic plasmonic
      grating. The self-collimation effect is understood from the local anisotropy of
      the isofrequency surface of the grating in the vicinity of the bandgap. The
      properties of the beams are analyzed by leakage radiation microscopy and show to
      an unprecedented level significantly reduced diffraction as compared with plasmon
      beams propagating on a flat metal film.

PMID- 22660073
TI  - Superbunched bright squeezed vacuum state.
AB  - In this Letter, we experimentally study the statistical properties of a bright
      squeezed vacuum state containing up to 10(13) photons per mode (10 MUJ per
      pulse), produced via high-gain parametric down conversion (PDC). The effects of
      bunching and superbunching of photons were observed for a single-mode PDC
      radiation by second-order intensity correlation function measurements with analog
      detectors.

PMID- 22660074
TI  - Four-step spatial phase-shifting shearing interferometry from moire configuration
      by triple gratings.
AB  - A spatial phase-shifting shearing interferometry is presented in this paper. The
      whole optical configuration is simple and consists of three Ronchi gratings. Four
      phase-shifted shearing interferograms can be obtained simultaneously. The
      explicit intensity distributions of shearing interferograms are given and a
      corresponding four-step spatial phase-shifting algorithm is proposed to extract
      phase information from the new interferometry. This spatial phase-shifting
      configuration is applied to extract phase projection of a propane flame and a
      mathematical error analysis is presented.

PMID- 22660075
TI  - Long-term frequency stabilization of a 16 m(2) ring laser gyroscope.
AB  - A 16 m(2) helium-neon-based ring laser gyroscope has been frequency stabilized to
      within 60 kHz over a period of three months. This is achieved using the beat
      frequency of the ring laser and an iodine-stabilized reference laser as a
      feedback signal on a pressure vessel enclosing the entire laser, under servo
      control. We demonstrate that we can compensate for, and thereby negate the
      influence of, atmospheric pressure variations, which are considerable sources of
      long-term instability.

PMID- 22660076
TI  - Electrostrictive counterforce on fluid microdroplet in short laser pulse.
AB  - When a micrometer-sized fluid droplet is illuminated by a laser pulse, there is a
      fundamental distinction between two cases. If the pulse is short in comparison
      with the transit time for sound across the droplet, the disruptive optical
      Abraham-Minkowski radiation force is countered by electrostriction, and the net
      stress is compressive. In contrast, if the pulse is long on this scale,
      electrostriction is cancelled by elastic pressure and the surviving term of the
      electromagnetic force, the Abraham-Minkowski force, is disruptive and deforms the
      droplet. Ultrashort laser pulses are routinely used in modern experiments, and
      impressive progress has moreover been made on laser manipulation of liquid
      surfaces in recent times, making a theory for combining the two pertinent. We
      analyze the electrostrictive contribution analytically and numerically for a
      spherical droplet.

PMID- 22660077
TI  - Absolute fast axis determination using non-polarization-maintaining fiber-based
      polarization-sensitive optical coherence tomography.
AB  - We report on a new calibration technique that permits the accurate extraction of
      sample Jones matrix and hence fast-axis orientation by using fiber-based
      polarization-sensitive optical coherence tomography (PS-OCT) that is completely
      based on non-polarization-maintaining fiber such as SMF-28. In this technique,
      two quarter-wave plates (QWPs) are used to completely specify the parameters of
      the system fibers in the sample arm so that the Jones matrix of the sample can be
      determined directly. The device was validated on measurements of a QWP and an
      equine tendon sample by a single-mode fiber-based swept-source PS-OCT system.

PMID- 22660078
TI  - Optical manipulation of particle ensembles in air.
AB  - We demonstrate that airborne light-absorbing particles can be photophoretically
      trapped and moved inside an optical lattice formed by multiple-beam interference.
      This technique allows simultaneous three-dimensional manipulation of multiple
      micro-objects in gases.

PMID- 22660079
TI  - Fast model-based multispectral imaging using nonnegative principal component
      analysis.
AB  - Estimation of the spectral reflectance of a scene is a critical problem in image
      processing and computer vision applications. Model-based multispectral imaging,
      one of the spectral reflectance estimation methods, can effectively reconstruct
      the full spectrum using a small number of camera shots. However, it is based on
      iterative optimization and, thus, is computationally too intensive. In this
      Letter, we modify the iterative optimization problem to a closed-form problem
      using nonnegative principal component analysis. The proposed method can
      substantially reduce the computational cost while maintaining the accuracy.

PMID- 22660080
TI  - Femtosecond laser fabricated micro Mach-Zehnder interferometer with Pd film as
      sensing materials for hydrogen sensing.
AB  - In this paper, a femtosecond laser fabricated fiber inline micro Mach-Zehnder
      interferometer with deposited palladium film for hydrogen sensing is presented.
      Simulation results show that the transmission spectrum of the interferometer is
      critically dependent on the microcavity length and the refractive index of Pd
      film and a short microcavity length corresponds to a high sensitivity. The
      experimental results obtained in the wavelength region of 1200-1400 nm, and in
      the hydrogen concentration range of 0-16%, agree well with that of the
      simulations. The developed system has high potential in hydrogen sensing with
      high sensitivity.

PMID- 22660081
TI  - Measurement of three-dimensional deformation vectors with digital holography and
      stereophotogrammetry.
AB  - We present a method to determine the three-dimensional (3D) deformation vectors
      of an arbitrary stressed object by combining stereophotogrammetry and digital
      holography in a setup with four cameras. The resulting data consists of a dense
      3D point cloud, where every point is associated with a deformation vector. Our
      method is able to calculate the deformation without prior knowledge of the
      sensitivity vectors or the object surface. In the experimental setup only the
      base distance of the cameras needs to be known.

PMID- 22660082
TI  - Localized mode hybridization by fine tuning of two-dimensional random media.
AB  - We study numerically the interaction of spatially localized modes in strongly
      scattering two-dimensional (2D) media. We move eigenvalues in the complex plane
      by changing gradually the index of a single scatterer. When spatial and spectral
      overlap is sufficient, localized states couple, and avoided level crossing is
      observed. We show that local manipulation of the disordered structure can couple
      several localized states to form an extended chain of hybridized modes crossing
      the entire sample, thus changing the nature of certain modes from localized to
      extended in a nominally localized disordered system. We suggest such a chain in
      2D random systems is the analog of one-dimensional necklace states, the
      occasional open channels predicted by Pendry [Physics 1, 20 (2008).] through
      which the light can sneak through an opaque medium.

PMID- 22660083
TI  - Nanofiber Fabry-Perot microresonator for nonlinear optics and cavity quantum
      electrodynamics.
AB  - We experimentally realize a Fabry-Perot-type optical microresonator near the
      cesium D2 line wavelength based on a tapered optical fiber, equipped with two
      fiber Bragg gratings that enclose a subwavelength diameter waist. Owing to the
      very low taper losses, the finesse of the resonator reaches F=86 while the on
      resonance transmission is T=11%. The characteristics of our resonator fulfill the
      requirements of nonlinear optics and cavity quantum electrodynamics in the strong
      coupling regime. These characteristics, combined with the demonstrated ease of
      use and advantageous mode geometry, open a realm of applications.

PMID- 22660084
TI  - Microfluidic integration of photonic crystal fibers for online photochemical
      reaction analysis.
AB  - Liquid-filled hollow-core photonic crystal fibers (HC-PCFs) are perfect
      optofluidic channels, uniquely providing low-loss optical guidance in a liquid
      medium. As a result, the overlap of the dissolved specimen and the intense light
      field in the micronsized core is increased manyfold compared to conventional
      bioanalytical techniques, facilitating highly-efficient photoactivation
      processes. Here we introduce a novel integrated analytical technology for
      photochemistry by microfluidic coupling of a HC-PCF nanoflow reactor to
      supplementary detection devices. Applying a continuous flow through the fiber, we
      deliver photochemical reaction products to a mass spectrometer in an online and
      hence rapid fashion, which is highly advantageous over conventional cuvette-based
      approaches.

PMID- 22660085
TI  - Full-range, complex spatial light modulator for real-time holography.
AB  - We demonstrate a full-range complex and transmissive spatial light modulator
      (SLM) for simultaneous and independent amplitude and phase modulation of an input
      wave field. Arbitrary scalar complex optical fields are generated by stacking a
      pixelated liquid crystal display operating in phase-only (2pi) modulation with
      passive polarization-sensitive components. The principle is based on optical
      combining the light fields of two neighboring phase-only modulating pixels, which
      were made orthogonally polarized by a structured half-wave plate, then passing
      through a birefringent plate to laterally shift one of the beams collinear to the
      other, and finally bringing to interference by a linear polarizer. Complex
      modulation by the proposed SLM is experimentally verified in monochrome green
      operation.

PMID- 22660086
TI  - Passive component based multifunctional Jones matrix swept source optical
      coherence tomography for Doppler and polarization imaging.
AB  - We present a fiber based multifunctional Jones matrix swept source optical
      coherence tomography (SS-OCT) system for Doppler and polarization imaging. Jones
      matrix measurement without using active components such as electro-optic
      modulators is realized by incident polarization multiplexing based on independent
      delay of two orthogonal polarization states and polarization diversity detection.
      In addition to polarization sensitivity, this system measures Doppler flow
      without extra hardware for phase stabilized SS-OCT detection. An eighth-wave
      plate was measured to demonstrate the polarization detection accuracy. The optic
      nerve head of a retina was measured in vivo. Detailed vasculature and
      birefringent structures were investigated simultaneously.

PMID- 22660087
TI  - Fluctuation polarimetry.
AB  - We examine the relationship between the strength of the intensity fluctuations
      and the polarimetric properties of a random electromagnetic field composed of a
      Gaussian, random field, and nonrandom field, and we present a method for
      determining the state of polarization of the Gaussian random field. The approach
      relies on incoherently mixing a Gaussian random field with a controllable
      reference field and measuring the intensity fluctuations of their superposition.
      We demonstrate that by controlling the reference field, the full polarimetric
      information about the Gaussian random field can be uniquely determined.

PMID- 22660088
TI  - "Ideal" optical delay lines based on tailored-coupling and reflecting, coupled
      resonator optical waveguides.
AB  - We present a design of "ideal" optical delay lines (i.e., constant amplitude and
      constant group delay over the desired bandwidth). They are based on reflection
      from coupled-resonator optical waveguides (CROWs). The inter-resonator coupling
      coefficients are tailored and decrease monotonically with the distance from the
      input to realize all-pass Bessel filters. The tailored coupling coefficients
      result in a frequency-dependent propagating distance which compensates for the
      group velocity dispersion of CROWs. We present a simple formalism for deriving
      the time-domain coupling coefficients and convert these coefficients to field
      coupling coefficients of ring resonators. The reflecting CROWs possess a delay
      bandwidth product of 0.5 per resonator, larger than that of any kind of
      transmitting CROW. In the presence of uniform gain, the gain enhanced by slow
      light propagation and the constant group delay result in efficient and dispersion
      free amplifiers.

PMID- 22660090
TI  - Second-Stokes YVO4/Nd:YVO4/YVO4 self-frequency Raman laser.
AB  - We demonstrated an efficient second-Stokes Raman laser emission at 1313 nm based
      on self-frequency stimulated Raman scattering from a diode-end-pumped actively Q
      switched YVO(4)/Nd:YVO(4)/YVO(4) laser at 1064 nm for the first time, to the
      authors' knowledge. A double-end diffusion-bonded Nd:YVO(4) composite crystal was
      adopted for sufficiently improving the thermal lensing effect in the course of
      self-frequency stimulated Raman scattering operation. With an incident pump power
      of 14.6 W and a pulse repetition (PRR) of 40 kHz, a maximum average output power
      of 2.34 W was obtained, corresponding to an optical-to-optical conversion
      efficiency of 16%. Pulse width and peak power were 1.2 ns and 49 kW,
      respectively.

PMID- 22660091
TI  - Dynamic control of the operation regimes of a mode-locked fiber laser based on
      intracavity polarizing fibers: experimental and theoretical validation.
AB  - An intracavity polarizing fiber is proposed to control the emission regime of a
      passively mode-locked fiber laser. Stable operation in self-starting high and low
      dispersion soliton mode-locking and 100 GHz multiwavelength regimes is
      demonstrated through numerical simulations and experimental validation. Mode
      locking stability is ensured by a saturable absorber in the ring cavity. The
      effective selection of operation regime is dynamically carried out by controlling
      the intracavity polarization state.

PMID- 22660092
TI  - Optical microfiber mode interferometer for temperature-independent refractometric
      sensing.
AB  - We report on a functional optical microfiber mode interferometer and its
      applications for absolute, temperature-insensitive refractive index sensing. A
      standard optical fiber was tapered down to 10 MUm. The central part of the taper,
      i.e., the microfiber, is connected to the untapered regions with two identical
      abrupt transitions. The transmission spectrum of our device exhibited a
      sinusoidal pattern due to the beating between modes. In our interferometer the
      period of the pattern-an absolute parameter-depends strongly on the surrounding
      refractive index but it is insensitive to temperature changes. The period, hence
      the external index, can be accurately measured by taking the fast Fourier
      transform (FFT) of the detected interference pattern. The measuring refractive
      index range of the device here proposed goes from 1.33 to 1.428 and the maximum
      resolution is on the order of 3.7*10(-6).

PMID- 22660093
TI  - Coherence of a single mode InAlGaAs/InP cylinderical microlaser with two output
      ports.
AB  - We experimentally investigate the coherence of a single mode InAlGaAs/InP
      cylindrical microlaser with two output waveguides. For a cylindrical microlaser
      with a radius of 15 MUm and two 2 MUm-wide output waveguides, single mode
      operation with a side mode suppression ratio of 30 dB is realized, and a far
      field interferometric pattern similar to a Young's interferometer is observed.
      The results indicate that the microlasers with two output waveguides can be used
      as the light source for an optical sensor by monitoring the phase change of the
      output emission from one port versus that of the other port.

PMID- 22660095
TI  - Coupling plasmons and dyakonons.
AB  - We study the coupling of plasmons and Dyakonov surface waves propagating at the
      interfaces between isotropic-birefringent-metal layered structures. Efficient
      coupling is shown to occur with a proper choice of the crystal birefringence, the
      refractive index of the isotropic medium, and the light propagation direction
      relative to the crystal optical axis. In the case of low-loss metals, coupling
      efficiencies as high as 90% are predicted to be possible.

PMID- 22660094
TI  - Phase-shifted Fresnel axicon.
AB  - We propose an optical element: a phase-shifted Fresnel axicon for generation of
      multiple Bessel beams. By giving a binary phase modulation to the standard
      Fresnel axicon, the proposed element is generated. The phase profile of the
      binary phase modulation is engineered to generate two and three Bessel beams of
      equal intensities. This composite optical element is fabricated using electron
      beam direct writing. The performance of the fabricated device is evaluated using
      a semiconductor laser, and the generation of two and three Bessel beams is
      successfully demonstrated.

PMID- 22660096
TI  - 520 mJ langasite electro-optically Q-switched Cr, Tm, Ho:YAG laser.
AB  - A flash lamp pumped 2.09 MUm Cr, Tm, Ho:YAG laser utilizing a self-grown
      La(3)Ga(5)SiO(14) crystal as the electro-optic Q-switch generator is proposed and
      demonstrated for the first time. Operating at 3 Hz repetition rate, 520 mJ pulse
      energy with 35 ns pulse width is achieved by optimizing the Q-switch delay time
      and compensating for the thermal depolarization with a quarter-wave plate. The
      corresponding peak power is 14.86 MW, and the Q-switched-to-normal-mode energy
      extraction efficiency is 66.3%. To our knowledge, this Q-switched giant pulse is
      the best result reported to date in 2.09 MUm laser resonator.

PMID- 22660097
TI  - Long-external-cavity distributed Bragg reflector laser with subkilohertz
      intrinsic linewidth.
AB  - We report on a simple, compact, and robust 780 nm distributed Bragg reflector
      laser with subkilohertz intrinsic linewidth. An external cavity with optical path
      length of 3.6 m, implemented with an optical fiber, reduces the laser frequency
      noise by several orders of magnitude. At frequencies above 100 kHz the frequency
      noise spectral density is reduced by over 33 dB, resulting in an intrinsic
      Lorentzian linewidth of 300 Hz. The remaining low-frequency noise is easily
      removed by stabilization to an external reference cavity. We further characterize
      the influence of feedback power and current variation on the intrinsic linewidth.
      The system is suitable for experiments requiring a tunable laser with narrow
      linewidth and low high-frequency noise, such as coherent optical communication,
      optical clocks, and cavity QED experiments.

PMID- 22660098
TI  - Transient reflectance spectra of adaptive filters based on dynamic population
      gratings.
AB  - We propose a novel and practical method to exactly measure the transient
      reflectance spectra (TRS) of the adaptive filters based on dynamic population
      gratings. The modulating signals applied to the laser source play an important
      role. We specially designed a train of triangular amplitude modulated pulses with
      a small duty to modulate the laser frequency, and then the TRS was obtained from
      the grating responses to this pulse train. The measured half-zero-point
      bandwidths of the filter with and without 2.6 m cavity length are 20 and 60 MHz,
      respectively. Our research also indicates that the relatively high input power
      and a short cavity length may enhance the antiperturbation ability of lasers.

PMID- 22660099
TI  - Transmitted wavefront error of a volume phase holographic grating at cryogenic
      temperature.
AB  - This paper describes the results of transmitted wavefront error (WFE)
      measurements on a volume phase holographic (VPH) grating operating at a
      temperature of 120 K. The VPH grating was mounted in a cryogenically compatible
      optical mount and tested in situ in a cryostat. The nominal root mean square
      (RMS) wavefront error at room temperature was 19 nm measured over a 50 mm
      diameter test aperture. The WFE remained at 18 nm RMS when the grating was
      cooled. This important result demonstrates that excellent WFE performance can be
      obtained with cooled VPH gratings, as required for use in future cryogenic
      infrared astronomical spectrometers planned for the European Extremely Large
      Telescope.

PMID- 22660100
TI  - Fiber ring laser interrogated zeolite-coated singlemode-multimode-singlemode
      structure for trace chemical detection.
AB  - Zeolite thin films were synthesized on the claddingless multimode portion of a
      singlemode-multimode-singlemode (SMS) fiber structure to construct a chemical
      vapor sensor. The zeolite-coated SMS structure was inserted into a fiber ring
      amplifier to produce a laser line. Combining the strong molecular adsorption
      capability of the nanoporous zeolite and the high signal-to-noise ratio of the
      fiber laser, the device was demonstrated for chemical vapor sensing with a low
      detection limit.

PMID- 22660101
TI  - Pupil-segmentation-based adaptive optical correction of a high-numerical-aperture
      gradient refractive index lens for two-photon fluorescence endoscopy.
AB  - The intrinsic aberrations of high-NA gradient refractive index (GRIN) lenses
      limit their image quality as well as field of view. Here we used a pupil
      segmentation-based adaptive optical approach to correct the inherent aberrations
      in a two-photon fluorescence endoscope utilizing a 0.8 NA GRIN lens. By
      correcting the field-dependent aberrations, we recovered diffraction-limited
      performance across a large imaging field. The consequent improvements in imaging
      signal and resolution allowed us to detect fine structures that were otherwise
      invisible inside mouse brain slices.

PMID- 22660102
TI  - Class A mode-locked semiconductor ring laser.
AB  - We experimentally demonstrate low-repetition-rate mode-locked operation of a
      macroscopic semiconductor ring laser. Since antiphase periodic pulses are
      observed only when the two directions of operation are constrained to spatially
      overlap in the semiconductor medium, we interpret this regime as a result of
      coupling and competition between clockwise and counterclockwise emission
      directions. Because of its time constants and the possibility of unidirectional
      operation, the device could be highly suitable for the generation of temporal
      cavity solitons.

PMID- 22660103
TI  - Combined effects of microcavity and dielectric capping layer on bidirectional
      organic light-emitting diodes.
AB  - We report on highly enhanced and controlled light outcoupling of bidirectional
      organic light-emitting diodes by introduction of an enhanced microcavity
      structure as well as an organic capping layer (OC). Combining both OC and
      microcavity, we find that the overall external quantum, as well as current
      efficiency (CE), can be greatly enhanced. Especially, the CE with an appropriate
      thickness of OC is almost 1.75 times larger than that of the reference device
      without OC. Furthermore, we also analyze our devices with a numerical optical
      model calculating the flux of outcoupled photons, and compare theoretical
      predictions with our experimental results.

PMID- 22660104
TI  - Mechano-optical wavelength tuning in a photonic crystal microcavity with sub-1 V
      drive voltage.
AB  - A micro-bimorph cantilever with self-aligned nanotips is monolithically
      integrated with a photonic crystal based device using optical and deep UV
      lithography techniques. Upon electrostatic actuation, the dielectric nanotips
      perturb the optical field, providing electromechano-optical modulation of light.
      Static tuning of the optical transmission spectra by more than 600 pm is measured
      with a sub-1 V drive voltage, resulting in a modulation as high as 21 dB. The
      observed strong electromechano-optical effect may find application in power
      efficient devices for optical communication networks, such as wavelength routing
      elements.

PMID- 22660105
TI  - Multidimensional imaging using compressive Fresnel holography.
AB  - We propose a generalized framework for single-shot acquisition of
      multidimensional objects using compressive Fresnel holography. A multidimensional
      object with spatial, spectral, and polarimetric information is propagated with
      the Fresnel diffraction, and the propagated signal of each channel is observed by
      an image sensor with randomly arranged optical elements for filtering. The object
      data are reconstructed using a compressive sensing algorithm. This scheme is
      verified with numerical experiments. The proposed framework can be applied to
      imageries for spectrum, polarization, and so on.

PMID- 22660106
TI  - Quantitative phase microscopy of biological samples using a portable
      interferometer.
AB  - This Letter presents the tau interferometer, a portable and inexpensive device
      for obtaining spatial interferograms of microscopic biological samples without
      the strict stability and the highly coherent illumination that are usually
      required for interferometric microscopy setups. The device is built using off-the
      shelf optical elements and can easily operate with low-coherence illumination,
      while being positioned in the output of a conventional inverted microscope. The
      interferograms are processed into the quantitative amplitude and phase profiles
      of the sample. Based on the phase profile, the optical-path-delay profile is
      obtained with temporal stability of 0.18 nm and spatial stability of 0.42 nm.
      Further experimental demonstration of using the tau interferometer for imaging
      the quantitative thickness profile of a live red blood cell is provided.

PMID- 22660107
TI  - Improving efficiency roll-off in phosphorescent OLEDs by modifying the exciton
      lifetime.
AB  - Studies on phosphorescent organic light emitting devices (PhOLEDs) with
      phosphorescent emitter, fac-tris (2-phenylpyridine) iridium (Ir(ppy)(3)), show
      that the lifetime of triplet exciton is modified by surface plasmon coupling of
      Au nanoparticles (NPs). Interactions between the triplet exciton and gold (Au)
      nanoparticles (NPs) lead to a decrease in the exciton lifetime and result in the
      spontaneous emission decay rate of triplet exciton faster as the distance between
      the phosphorescent material and the Au NPs becomes smaller. This interaction
      reduces the efficiency roll-off of Au NPs containing device. These results
      provide new guides for device design to improve efficiency performance.

PMID- 22660108
TI  - Frequency-modulated continuous-wave lidar using I/Q modulator for simplified
      heterodyne detection.
AB  - A frequency-modulated continuous-wave (FMCW) lidar is demonstrated with
      heterodyne detection. The lidar transmitter utilizes an electro-optic I/Q
      modulator for the first time to generate carrier-suppressed and frequency-shifted
      FM modulation. This eliminates the need for an acousto-optic frequency shifter
      commonly used in heterodyne lidar transmitters. It also allows the use of a much
      wider modulation bandwidth to improve the range resolution. The capability of
      complex optical field modulation of the I/Q modulator provides an additional
      degree of freedom compared with an intensity modulator, which will benefit future
      lidar applications.

PMID- 22660109
TI  - Low irradiance background limited type-II superlattice MWIR M-barrier imager.
AB  - We report a type-II superlattice mid-wave infrared 320*256 imager at 81 K with
      the M-barrier design that achieved background limited performance (BLIP) and ~99%
      operability. The 280 K blackbody's photon irradiance was limited by an aperture
      and a band-pass filter from 3.6 MUm to 3.8 MUm resulting in a total flux of
      ~5*10(12) ph.cm(-2).s(-1). Under these low-light conditions, and consequently the
      use of a 13.5 ms integration time, the imager was observed to be BLIP thanks to a
      ~5 pA dark current from the 27 MUm wide pixels. The total noise was dominated by
      the photon flux and read-out circuit which gave the imager a noise equivalent
      input of ~5*10(10) ph.cm(-2).s(-1) and temperature sensitivity of 9 mK with F/2.3
      optics. Excellent imagery obtained using a 1-point correction alludes to the
      array's uniform responsivity.

PMID- 22660110
TI  - 466 mW green light generation using annealed proton-exchanged periodically poled
      MgO: LiNbO3 ridge waveguides.
AB  - We report high-power efficient green light generation by frequency doubling from
      a periodically poled MgO doped LiNbO(3) ridge waveguide. The ridge waveguide is
      fabricated by the annealed proton-exchanging and precise diamond blade dicing
      techniques. The ridge structure exhibits a surface roughness of only 3.7 nm, and
      near-90 degrees  vertical sidewall. The total insertion loss of an 8.5 um wide
      and 1.4 cm long uncoated waveguide is 3.0 dB under direct fiber coupling. 466 mW
      of continuous-wave green light with an optical-to-optical conversion efficiency
      of 69.7% is obtained. To the best of our knowledge, this is the highest green
      light output power reached to date using a ridge-type LiNbO(3) waveguide device.
      Phase-matching temperature shift, tuning curve distortion, and waveguide loss
      increase are observed under high power operation. Our analysis shows that the
      photorefractive effect and the green induced infrared absorption are responsible
      for the observed phenomena, which becomes prominent under several megawatt per
      square centimeter power density.

PMID- 22660111
TI  - Experimental demonstration of subcarrier multiplexed quantum key distribution
      system.
AB  - We provide, to our knowledge, the first experimental demonstration of the
      feasibility of sending several parallel keys by exploiting the technique of
      subcarrier multiplexing (SCM) widely employed in microwave photonics. This
      approach brings several advantages such as high spectral efficiency compatible
      with the actual secure key rates, the sharing of the optical fainted pulse by all
      the quantum multiplexed channels reducing the system complexity, and the
      possibility of upgrading with wavelength division multiplexing in a two-tier
      scheme, to increase the number of parallel keys. Two independent quantum SCM
      channels featuring a sifted key rate of 10 Kb/s/channel over a link with quantum
      bit error rate <2% is reported.

PMID- 22660112
TI  - Frozen waves: experimental generation.
AB  - Frozen waves (FWs) are very interesting particular cases of nondiffracting beams
      whose envelopes are static and whose longitudinal intensity patterns can be
      chosen a priori. We present here for the first time (that we know of) the
      experimental generation of FWs. The experimental realization of these FWs was
      obtained using a holographic setup for the optical reconstruction of computer
      generated holograms (CGH), based on a 4-f Fourier filtering system and a nematic
      liquid crystal spatial light modulator (LC-SLM), where FW CGHs were first
      computationally implemented, and later electronically implemented, on the LC-SLM
      for optical reconstruction. The experimental results are in agreement with the
      corresponding theoretical analytical solutions and hold excellent prospects for
      implementation in scientific and technological applications.

PMID- 22660113
TI  - Broadband enhancement of spontaneous emission in a photonic-plasmonic structure.
AB  - We demonstrate that a broadband enhancement of spontaneous emission can be
      achieved within a photonic-plasmonic structure. The structure can strongly modify
      the spontaneous emission by exciting plasmonic modes. Because of the excited
      plasmonic modes, an enhancement up to 30 times is observed, leading to a 4 times
      broader emission spectrum. The reflectance measurement and the finite-difference
      time-domain simulation are carried out to support these results.

PMID- 22660114
TI  - Estimation of the droplet size spread with the laser induced fluorescence/Mie
      technique.
AB  - The laser measurement technique based on the ratio between the laser induced
      fluorescence (LIF) and the scattered light (Mie) intensities of droplets is
      presently limited to the evaluation of the Sauter mean diameter of the droplets.
      The important measurement of the droplet size spread is currently missing. An
      extension of the LIF/Mie technique for the measurement of droplet size spread is
      proposed here and is evaluated numerically. The method is based on the imperfect
      relationships between the scattered light intensity and the droplet surface area
      or the fluorescent light intensity and the droplet volume, which convey
      additional information that can be used to evaluate the droplet size spread.

PMID- 22660115
TI  - Linear birefringence in split-ring resonators.
AB  - We study polarization-dependent transmission of light through arrays of single
      slit split-ring resonator (SSRR) based systems at normal incidence using finite
      integration time domain (FITD) and finite element methods (FEM). It is found that
      a conventional planar array of SSRRs acts as an effective optical wave plate at
      certain polarizations of incident light. The effect is attributed to the
      intrinsic linear birefringence of individual SSRRs. A comparison is made with
      other split-ring resonator-based systems exhibiting wave-plate-like properties
      due to inter-SSRR coupling.

PMID- 22660116
TI  - In-line silica capillary tube all-silica fiber-optic Fabry-Perot interferometric
      sensor for detecting high intensity focused ultrasound fields.
AB  - Aiming at detecting high intensity focused ultrasound (HIFU) fields, this letter
      reports on a novel in-line silica capillary tube all-silica fiber-optic Fabry
      Perot (ILSCT-ASFP) interferometric sensor fabricated by splicing a commercially
      available silica capillary tube to two single-mode fibers. The experimental
      results show that such a novel ILSCT-ASFP interferometric sensor with a cavity
      length of ~60.76 MUm has an excellent fringe visibility of up to ~20 dB, and the
      fringe visibility is still good when the cavity length extends up to ~1031.07
      MUm. The measured wavelength-temperature sensitivity of 0.000858 nm/ degrees C
      shows that the wavelength drift of the fabricated ILSCT-ASFP interferometric
      sensor towards temperature is extremely low. Meanwhile, the measurement of HIFU
      fields by this novel sensor is demonstrated, and the experimental results
      indicate that the signal-to-noise ratio of the sensing system for sensing a 0.93
      MHz HIFU field with a pressure of 2.69 MPa in the focus area can reach 42.8 dB.
      The corresponding noise equivalent pressure is 0.0194 MPa, and the calculated
      acoustic sensitivity is 65.4 mV/MPa over a 2.5 MHz measurement bandwidth.

PMID- 22660117
TI  - Large prolongation of free-exciton photoluminescence decay in diamond by two
      photon excitation.
AB  - We report on time-resolved photoluminescence of a free-exciton in IIa chemical
      vapor deposition diamond crystal. Large difference between decay times for one-
      and two-photon excitation processes was observed. The longest room-temperature
      exciton photoluminescence lifetime tau(FE)=220 ns was obtained under two-photon
      excitation with a photon energy of 4.7 eV. The role of diffusion and surface
      recombination velocity in exciton photoluminescence dynamics was studied using a
      new optical method based on two-photon excited time-resolved photoluminescence.
      The measured room-temperature value of diffusion coefficient in diamond was D=40
      cm(2)/s.

PMID- 22660118
TI  - Hilbert reconstruction of phase-shifted second-harmonic holographic images.
AB  - New techniques are presented that make phase-shifting holography viable for
      second-harmonic generation (SHG) holography with weak object fields. We developed
      an intrinsic phase shift calibration of SHG holograms, an algorithm that extracts
      the reference and object intensity directly from a set of phase-shifted
      holographic data, and a more robust phase-shifting holography reconstruction
      algorithm based on pi-shifted hologram pairs that permits self-calibration of the
      phase shift and recovery of the complex field through a Hilbert transform.

PMID- 22660119
TI  - Coherence and polarization properties in speckle of totally depolarized light
      scattered by totally depolarizing media.
AB  - When a totally unpolarized light is scattered by a medium that spatially totally
      depolarizes incident polarized light, the scattered field presents an increase of
      the order described by the temporal degree of polarization. We analyze the
      behavior of some polarization and coherence properties in such a physical
      situation.

PMID- 22660120
TI  - Three-dimensional locating of paraxial point source with axicon.
AB  - This Letter presents a theoretical and experimental study of an axicon
      illuminated by an off-axis paraxial point source. The Fresnel diffraction
      integral is applied to show that a paraxial point source produces a Bessel beam.
      A simple analytical relationship is demonstrated between the location of the
      point source and the spatial frequency and the center of the resulting Bessel
      beam in the image plane of a camera. Finally, experimental verification is given
      by translating a point source of light along the optical axis of an axicon and
      comparing the resulting predicted and recorded beam intensity profiles. The
      resulting images are then analyzed to predict the location of the point source
      with excellent accuracy.

PMID- 22660121
TI  - Analytical approach to the impact of polarization aberration on lithographic
      imaging.
AB  - An analytical approach to the impact of polarization aberration on lithographic
      imaging is proposed. The linear relationship between image placement error (IPE)
      of alternating phase-shifting mask (Alt-PSM) and odd aberration items of
      polarization aberrations, as well as that between best focus shift (BFS) of Alt
      PSM and even aberration items of polarization aberrations are established by
      analytical equations, respectively. The validity of the linear relationships is
      demonstrated by numerical results. The differences and connections between scalar
      aberration and polarization aberration are briefly discussed based on these
      linear relationships.

PMID- 22660122
TI  - Stable generation of high-order harmonics of femtosecond laser radiation from
      laser produced plasma plumes at 1 kHz pulse repetition rate.
AB  - We present a method for the creation of stable weakly ionized plasmas from laser
      ablation of solid targets using a 1 kHz pulse repetition rate laser, which can be
      used for stable high-order harmonic generation from plasma plumes. The plasma
      plumes were generated from cylindrical rotating targets. Without target rotation
      the intensity of harmonics in the 40-80 nm range drops by more than one order of
      magnitude during less than 10(3) shots, while, with rotation of the target at
      typically 30 revolutions per minute, stable emission of high-order harmonics from
      aluminum plasma plumes with variation of less than 10% was maintained for >10(6)
      laser shots.

PMID- 22660123
TI  - Novel phase-coding method for absolute phase retrieval.
AB  - This Letter presents a novel absolute phase recovery technique with phase coding.
      Unlike the conventional gray-coding method, the codeword is embedded into the
      phase and then used to determine the fringe order for absolute phase retrieval.
      This technique is robust because it uses phase instead of intensity to determine
      codewords, and it could achieve a faster measurement speed, since three
      additional images can represent more than 8(2(3)) unique codewords for phase
      unwrapping. Experimental results will be presented to verify the performance of
      the proposed technique.

PMID- 22660124
TI  - Perfectly phase-matched third-order distributed feedback terahertz quantum
      cascade lasers.
AB  - We report a novel laser cavity design in third-order distributed feedback (DFB)
      terahertz quantum-cascade lasers based on a perfectly phase-matching technique.
      This approach substantially increases the usable length of the third-order DFB
      laser and leads to narrow beam patterns. Single frequency emissions from 151
      apertures (5.6 mm long device) are coherently added up to form a narrow beam with
      (FWHM~6*11 degrees ) divergence. A similar device with 40 apertures shows more
      than 5 mW of optical power with slope efficiency ~140 mW/A at 10 K pulsed
      operation.

PMID- 22660125
TI  - Multichannel Raman polarizer with suppressed relative intensity noise for
      wavelength division multiplexing transmission lines.
AB  - We propose a method of suppressing the relative intensity noise caused by
      polarization-dependent gain that is inherent to Raman polarizers (RPs). This
      method involves bit-synchronously scrambling the state of polarization of a pulse
      (bit) before the pulse enters the RP. The proposed solution works for RPs
      operating in a depleted regime and is compatible with multichannel
      configurations.

PMID- 22660126
TI  - Long-term carrier-envelope-phase-stable few-cycle pulses by use of the feed
      forward method.
AB  - The feed-forward technique has recently revolutionized carrier-envelope phase
      (CEP) stabilization, enabling unprecedented values of residual phase jitter.
      Nevertheless, its demonstrations have hitherto remained in a proof-of-principle
      state. Here we show that pulse quality and power issues can be solved, leading to
      few-cycle pulses with good beam quality. Making use of stable interferometers, we
      achieve day-long CEP-stable operation of the setup. Out-of-loop RMS phase noise
      amounts to less than 30 mrad in 20 s, with more than 24 h of CEP-locked operation
      being demonstrated.

PMID- 22660127
TI  - Fast and highly accurate boundary element method for scattering calculation of
      defective gratings.
AB  - A numerical scattering calculation method for defective gratings is proposed.
      This method is based on an integral equation method that computes a difference
      field distribution, which is the difference between the scattering fields with
      and without the defect, and it is possible to simulate the arbitrary (finite)
      size and shape of a defect in the grating without any limitation. A calculation
      example is also presented to demonstrate the fast convergence and high accuracy
      of this method.

PMID- 22660128
TI  - Novel coordinate system for Gaussian beam reflection.
AB  - A novel coordinate system for Gaussian beam reflection has been proposed in this
      Letter. Reflection from a spherical mirror is used to describe the novel
      coordinate system. One single segment of a general resonator is chosen to
      describe coordinate rotation in detail. Nonplanar ring resonators are chosen to
      show the application of the novel coordinate system. This novel coordinate system
      has been proved by two simple experiments and the problem existing in using the
      traditional coordinate system has been pointed out. This novel coordinate system
      is valuable for not only the designing of laser resonators but also Gaussian beam
      propagation analysis.

PMID- 22660129
TI  - Graphene mode-locked femtosecond laser at 2 MUm wavelength.
AB  - We experimentally demonstrated a passively mode-locked femtosecond laser by using
      a graphene-based saturable absorber mirror (graphene SAM) in the spectral region
      of 2 MUm. The graphene SAM was fabricated by transferring chemical-vapor
      deposited, high-quality, and large-area graphene on a highly reflective plane
      mirror. Stable mode-locked laser pulses as short as 729 fs were obtained with a
      repetition rate of 98.7 MHz and an average output power of 60.2 mW at 2018 nm.

PMID- 22660130
TI  - Enhanced deterministic phase retrieval using a partially developed speckle field.
AB  - A technique for enhanced deterministic phase retrieval using a partially
      developed speckle field (PDSF) and a spatial light modulator (SLM) is
      demonstrated experimentally. A smooth test wavefront impinges on a phase
      diffuser, forming a PDSF that is directed to a 4f setup. Two defocused speckle
      intensity measurements are recorded at the output plane corresponding to axially
      propagated representations of the PDSF in the input plane. The speckle intensity
      measurements are then used in a conventional transport of intensity equation
      (TIE) to reconstruct directly the test wavefront. The PDSF in our technique
      increases the dynamic range of the axial intensity derivative for smooth phase
      objects, resulting in a more robust solution to the TIE. The SLM setup enables a
      fast and accurate recording of speckle intensity. Experimental results are in
      good agreement with those obtained using the iterative phase retrieval and
      digital holographic methods of wavefront reconstruction.

PMID- 22660131
TI  - Focused cylindrical vector beam assisted microscopic pSPR biosensor with an ultra
      wide dynamic range.
AB  - A novel phase-sensitive surface plasmon resonance (pSPR) biosensor based on
      differential phase measurement between two cylindrical vector beams, namely
      radially polarized and azmuthally polarized beams, is proposed and studied in an
      inverted microscope. Different from a fixed angle or a relatively small angular
      range for SPR excitation in the attenuated total reflection (ATR) configuration,
      the signal beam focused by a total internal reflection fluorescence microscopic
      objective contains the entire angular range from 0 to the maximum angle given by
      the numerical aperture, leading to a dynamic range of 0.41 RIU which is over
      seven times wider than the best result of the ATR pSPR sensor. Moreover, with the
      technique of differential phase measurement between radial and azimuthal
      polarizations employed in our configuration, high sensitivity of +/-9.05*10(-8)
      refractive index unit/1 deg can simultaneously be achieved in principle. The
      proposed technique maintains the unique advantages in terms of securing high
      imaging resolution and sensitivity with an ultra-wide dynamic range
      simultaneously.

PMID- 22660132
TI  - Broadband circular polarizer based on high-contrast gratings.
AB  - A circular polarizer, which is composed of periodic and two-dimensional
      dielectric high-contrast gratings, is designed theoretically such that a unity
      conversion efficiency is achieved at lambda(0)=1.55 MUm. The operation is
      obtained by the achievement of the simultaneous unity transmission of transverse
      magnetic and transverse electric waves with a phase difference of pi/2, meaning
      that an optimized geometrical anisotropy is accomplished. By the utilization of
      the rigorous coupled-wave analysis and finite-difference time-domain methods, it
      is shown that a percent bandwidth of ~50% can be achieved when the operation
      bandwidth is defined as the wavelengths for which the conversion efficiency
      exceeds 0.9.

PMID- 22660133
TI  - Modeling of racetrack-resonator add-drop filters with arbitrary nonlinear
      directional couplers.
AB  - In this Letter we employ the general coupled-mode equations of the nonlinear
      directional coupler and demonstrate that the switching characteristics of
      prototypical nonlinear racetrack-resonator structures may differ considerably
      from those obtained when the standard, generally incorrect, coupled-mode
      equations are used.

PMID- 22660134
TI  - Femtosecond pulse parametric amplification at narrowband high power gas laser
      pumping.
AB  - In ultrashort pulse amplification a narrowband gas pump pulse laser has been used
      for the first time. An all-stage optical parametric chirped pulse amplifier
      (OPCPA) was driven by a single-shot iodine photodissociation laser. For the first
      time a broadband amplification was achieved in potassium dihydrogen phosphate
      crystal at 800 nm seeding. Ti:sapphire laser pulses stretched from 12.5 fs to 250
      ps were amplified and compressed to 27 fs at a 0.5 TW output power. The results
      suggest using narrowband high power gas lasers as OPCPA drivers to generate
      petawatt beams.

PMID- 22660135
TI  - Total absorption of TM polarized light in a 100 nm spectral band in a
      nanopatterned thin a-Si film.
AB  - We report a leaky-mode resonant absorber fashioned as one-dimensional
      nanopatterned ultra-thin films. This simple structure exhibits optical absorbance
      of ~66% in the 300-750 nm wavelength band, which is an ~60% increase relative to
      a comparable planar reference structure. The transverse-magnetic (TM) polarized
      light in the ~460-560 nm band is nearly totally absorbed. Applying a backside
      metal reflector raises the absorbance farther to ~73%.

PMID- 22660136
TI  - Stabilization of a premixed CH4/O2/N2 flame using femtosecond laser-induced
      plasma.
AB  - The influence of femtosecond laser-induced plasma (FLIP) on the stability of a
      premixed CH(4)/O(2)/N(2) flame is investigated at atmospheric pressure. The laser
      energy, laser repetition rate, the equivalence ratios, and the volume percentage
      of oxygen in O(2)/N(2) blends are varied. Our findings indicate that the flame
      blow-off velocity is a function of these parameters. It has been experimentally
      found that the flame blow-off velocity increases by a factor of two with FLIP
      than without FLIP. A high-repetition-rate and a great energy laser-induced plasma
      flameholding, as a non-intrusive optical flameholding, may be a feasible
      alternative for any combustor.

PMID- 22660137
TI  - Tuning the detection sensitivity: a model for axial backfocal plane
      interferometric tracking.
AB  - Backfocal plane (BFP) interferometry is a single particle tracking technique that
      allows one to measure minute displacements of a microscopic particle from the
      center of a beam's focus in three dimensions. In this Letter, we present a
      Fourier optics model to describe the interference effects that allow one to track
      the position of a particle moving along the optical axis. A detection numerical
      aperture is derived theoretically and confirmed experimentally, within which the
      interference intensity has a positive correlation with the axial position of the
      scatterer. For larger detection angles, the correlation is negative. The model
      helps to understand previously reported measurements and to optimize BFP
      interferometric tracking.

PMID- 22660138
TI  - Unidirectional and wavelength-selective photonic sphere-array nanoantennas.
AB  - We design a photonic sphere-array nanoantenna (NA) exhibiting both strong
      directionality and wavelength selectivity. Although the geometric configuration
      of the photonic NA resembles a plasmonic Yagi-Uda NA, it has different working
      principles and, most importantly, reduces the inherent metallic loss from
      plasmonic elements. For any selected optical wavelength, a sharp Fano resonance
      by the reflector is tunable to overlap spectrally with a wider dipole resonance
      by the sphere-chain director, leading to high directionality. This Letter
      provides design principles for directional and selective photonic NAs, which are
      particularly useful for photon detection and spontaneous emission manipulation.

PMID- 22660139
TI  - Optical fiber modulator derivates from hollow optical fiber with suspended core.
AB  - A fiber optic integrated modulation-depth-tunable modulator based on a type of
      hollow optical fiber with suspended core is proposed and investigated. We
      synthesized magnetic fluid containing superparamagnetic Fe(3)O(4) nanoparticles
      and encapsulated it in the hollow optical fiber as the cladding layer of the
      suspended core by fusing the hollow optical fiber with the multimode optical
      fibers. The light with a wavelength of 632.8 nm is coupled in and out of the
      modulating element by a tapering technique. Experimental results show that the
      light attenuation in the system can be greatly influenced by only 2.0*10(-2) MUL
      of the magnetic fluid under different magnetic field strengths. The saturated
      modulation depth is 43% when the magnetic field strength is 489 Oe. The response
      time of the system is <120 ms. Significantly, this work presents information for
      the development of all-fiber modulators, including other integrated electro-optic
      devices, such as optical switch, optical fiber filter, and magnetic sensors
      utilizing the special structure of this hollow optical fiber with suspended core
      and superparamagnetic magnetic fluid.

PMID- 22660140
TI  - Generation of intense single-order harmonic pulse in the vacuum ultraviolet
      region using a deep ultraviolet driving laser.
AB  - A 90 nm single-order harmonic pulse with a 200 nJ on-target pulse energy at 1 kHz
      was realized through a harmonic generation process with a 35 fs Ti:Sa third
      harmonic in a Kr gas cell.

PMID- 22660141
TI  - Self-focusing transmittances.
AB  - In this Letter, we describe the optical field associated with transmittances
      characterized by a slit-shaped curve. The influence of the curvature is that the
      diffraction field generates focusing regions. The focusing geometry corresponds
      to the geometry of the transmittance curve, except for scaling, rotations or
      translations. A relevant point is that the changes in the morphology of the
      diffraction field are bounded by the focusing regions. Our experimental and
      computational results are in good agreement with the theoretical predictions.

PMID- 22660142
TI  - Optimal crystal geometry and orientation in electric field sensing using electro
      optic sensors.
AB  - For optimal sensitivity in electric field measurements, electro-optic (EO)
      crystals are typically selected based on their EO coefficients and dielectric
      constants. However, the conventional figure of merit yields sensitivity
      predictions regarding EO materials that are inconsistent with experimental data.
      In this Letter, we demonstrate that depolarization effects, which are often
      ignored, can dramatically enhance responsivity depending on the shape and
      orientation of the EO crystal. For optimal sensitivity, these effects are best
      exploited in longitudinal EO sensors, where they yield an optical modulation
      depth that increases quadratically with crystal length.

PMID- 22660143
TI  - Supercontinuum generation in short tellurite microstructured fibers pumped by a
      quasi-cw laser.
AB  - We investigate supercontinuum (SC) generation in highly nonlinear tellurite
      microstructured fibers pumped by a continuous wave (cw)/quasi-cw laser. We
      investigate two types of tellurite fibers. One type has the constant core
      diameter, and the other type has a longitudinally varying core diameter. For the
      fibers with a constant core diameter, when pumped in the anomalous dispersion
      region, the SC is symmetric in a fiber that has a zero dispersion wavelength
      close to the pump wavelength. For the fibers with a longitudinally varying
      diameter, the calculated phase-matching conditions show that they have a broad
      wavelength range of dispersive waves, and therefore the measured SC spectrum can
      be broader than one octave. In this work, the fiber lengths are as short as
      several tens of centimeters, and the pump power is in the watt level.

PMID- 22660144
TI  - Three-dimensional integral imaging with improved visualization using subpixel
      optical ray sensing.
AB  - In this Letter, we propose an improved three-dimensional (3D) image
      reconstruction method for integral imaging. We use subpixel sensing of the
      optical rays of the 3D scene projected onto the image sensor. When reconstructing
      the 3D image, we use a calculated minimum subpixel distance for each sensor pixel
      instead of the average pixel value of integrated pixels from elemental images.
      The minimum subpixel distance is defined by measuring the distance between the
      center of the sensor pixel and the physical position of the imaging lens point
      spread function onto the sensor, which is projected from each reconstruction
      point for all elemental images. To show the usefulness of the proposed method,
      preliminary 3D imaging experiments are presented. Experimental results reveal
      that the proposed method may improve 3D imaging visualization because of the
      superior sensing and reconstruction of optical ray direction and intensity
      information for 3D objects.

PMID- 22660145
TI  - Engineering the dispersion of metamaterial surface for broadband infrared
      absorption.
AB  - We propose a broadband infrared absorber by engineering the frequency dispersion
      of metamaterial surface (metasurface) to mimic an ideal absorbing sheet. With a
      thin layer of structured nichrome, a polarization-independent absorber with
      absorption larger than 97% is numerically demonstrated over a larger than one
      octave bandwidth. It is shown that the bandwidth enhancement is related with the
      transformation of the Drude model of free electron gas in metal film to the
      Lorentz oscillator model of a bound electron in the structured metallic surface.
      We believe that the concept of dispersion engineering may provide helpful
      guidance for the design of a broadband absorber.

PMID- 22660146
TI  - Two-dimensional nonlinear beam shaping.
AB  - We develop a technique for two-dimensional arbitrary wavefront shaping in
      quadratic nonlinear crystals by using binary nonlinear computer generated
      holograms. The method is based on transverse illumination of a binary modulated
      nonlinear photonic crystal, where the phase matching is partially satisfied
      through the nonlinear Raman-Nath process. We demonstrate the method
      experimentally showing a conversion of a fundamental Gaussian beam pump light
      into three Hermite-Gaussian and three Laguerre-Gaussian beams in the second
      harmonic. Two-dimensional binary nonlinear computer generated holograms open wide
      possibilities in the field of nonlinear beam shaping and mode conversion.

PMID- 22660147
TI  - Spatial coherence properties of surface plasmon investigated by Young's slit
      experiment.
AB  - In this Letter, we present an original method to extract the optical properties
      of surface plasmon polaritons (SPPs) on silver surfaces. A two Young's slit
      experiment combined with a leakage radiation microscope has been built. By
      correlating both imagery and coherence measurements on the same area, we are able
      to address the evolution of the SPP spatial coherence along its propagation. The
      proposed method could also be useful to explore the properties of complex
      plasmonic systems.

PMID- 22660148
TI  - Collection efficiency of scattered light in single-ended optical fiber sensors.
AB  - Optical fibers allow a variety of spectroscopic sensing methods to be implemented
      in a single-ended backscattering geometry. Taking multimode fibers with surface
      enhanced Raman scattering active tips as a model system, it is shown that the
      remote single-ended collection geometry can be relatively inefficient in
      comparison to the performance of the underlying sensor structure. Therefore the
      performance of the single-ended geometry has been compared to the analogous
      sensor structure on a nonguiding silica glass substrate. While part of the
      reduction in collection efficiency can be attributed to mismatches between the
      numerical aperture of the collection optics and that of the fiber, this study
      suggests that there can be an additional loss due to a mismatch between the
      confocal area of the collection optics and the area of the fiber core. This
      effect is most significant for high numerical aperture objectives. However, the
      collection efficiency is somewhat higher than would be expected from a simple
      area ratio analysis. This can be attributed to the graded-index fiber used in the
      model system and the relaxation of confocal requirements in the longitudinal
      direction.

PMID- 22660150
TI  - Nonlocality in PT-symmetric waveguide arrays with gain and loss.
AB  - We demonstrate that light propagation in waveguide arrays that include PT
      symmetric structures can exhibit strongly nonlocal sensitivity to topology of the
      array at fixed other parameters. We consider an array composed of lossless
      waveguides, that includes a pair of PT-symmetric waveguides with balanced gain
      and loss, and reveal that PT-symmetry breaking thresholds are different for
      planar and circular array configurations. These results demonstrate that PT
      symmetric structures can offer new regimes for optical beam shaping compared to
      conservative structures.

PMID- 22660149
TI  - Actively Q-switched 2.9 MUm Ho(3+)Pr(3+)-doped fluoride fiber laser.
AB  - We report an efficient Q-switched Ho(3+)Pr(3+)-doped fluoride fiber laser,
      producing a peak power of 77 W, with pulse width of 78 ns. A slope efficiency of
      20% with respect to the launched pump power was achieved. A TeO(2) acousto-optic
      modulator allowed continuous tunability of the pulse repetition frequency from 40
      to 300 kHz.

PMID- 22660151
TI  - X-ray in-line phase tomography of multimaterial objects.
AB  - We present a method for phase retrieval from x-ray Fresnel diffraction patterns
      for multimaterial objects. Previously, homogeneous object assumptions have been
      used and have been introduced in the Radon domain. Here, we apply prior knowledge
      in the object domain, which permits the introduction of multiple materials. This
      is achieved first by a tomographic reconstruction of an attenuation scan and then
      introduction of the prior followed by a forward projection step to yield the a
      priori phase maps. The method is applied to the reconstruction of an object of
      known composition consisting of both soft and hard materials and is shown to
      perform better than previously proposed algorithms.

PMID- 22660152
TI  - Holographic generation of a class of nondiffracting fields with optimum
      efficiency.
AB  - We discuss the accurate generation of complex optical fields using phase
      holograms that provide the optimum diffraction efficiency. In each considered
      case, the phase modulation of the employed hologram is identical to the phase of
      the desired optical field. We show that periodic and quasiperiodic nondiffracting
      optical fields, mathematically obtained through the superposition of multiple
      plane waves, can be generated with high fidelity using this approach.

PMID- 22660153
TI  - Gain and lasing of optically pumped metastable rare gas atoms.
AB  - Optically pumped alkali vapor lasers are currently being developed in several
      laboratories. The objective is to construct high-powered lasers that also exhibit
      excellent beam quality. Considerable progress has been made, but there are
      technical challenges associated with the reactivity of the metal atoms. Rare gas
      atoms (Rg) excited to the np(5)(n+1)s (3)P(2) configuration are metastable and
      have spectral properties that are closely similar to those of the alkali metals.
      In principle, optically pumped lasers could be constructed using excitation of
      the np(5)(n+1)p<-np(5)(n+1)s transitions. We have demonstrated this potential by
      observing gain and lasing for optically pumped Ar(*), Kr(*) and Xe(*). Three
      level lasing schemes were used, with He or Ar as the collisional energy transfer
      agent that established the population inversion. These laser systems have the
      advantage of using inert reagents that are gases at room temperature.

PMID- 22660154
TI  - Anyons in one-dimensional lattices: a photonic realization.
AB  - Anyons are nonlocal quasi-particles carrying fractional statistics that
      interpolate between bosons and fermions. Here we propose a photonic realization
      of anyons moving on a one-dimensional lattice, which is based on light transport
      in an engineered square array of optical waveguides with a helically bent axis.
      Our photonic simulator enables visualization of the nonlocal nature of anyons in
      Fock space and the persistence of correlated tunneling even in the absence of
      particle interaction.

PMID- 22660155
TI  - Random bit generation using an optically injected semiconductor laser in chaos
      with oversampling.
AB  - Random bit generation is experimentally demonstrated using a semiconductor laser
      driven into chaos by optical injection. The laser is not subject to any feedback
      so that the chaotic waveform possesses very little autocorrelation. Random bit
      generation is achieved at a sampling rate of 10 GHz even when only a fractional
      bandwidth of 1.5 GHz within a much broader chaotic bandwidth is digitized. By
      retaining only 3 least significant bits per sample, an output bit rate of 30 Gbps
      is attained. The approach requires no complicated postprocessing and has no
      stringent requirement on the electronics bandwidth.

PMID- 22660156
TI  - Scalar soliton generation in all-polarization-maintaining, graphene mode-locked
      fiber laser.
AB  - All-polarization-maintaining, self-starting Erbium-doped fiber laser based on
      graphene-saturable absorber is presented. Scalar soliton pulses with 570 fs
      duration and 114.1 MHz repetition rate were achieved at a 1557 nm center
      wavelength and with 6 nm bandwidth. The graphene-saturable absorber was formed by
      mechanical exfoliation of pure graphite. The laser was environmentally stable and
      could operate for long periods of time with linearly polarized output and degree
      of polarization at the level of 98%.

PMID- 22660157
TI  - Subfrequency noise signal extraction in fiber-optic strain sensors using
      postprocessing.
AB  - Laser frequency fluctuations typically limit the performance of high-resolution
      interferometric fiber strain sensors. Using time delay interferometry, we
      demonstrate a frequency noise immune fiber sensing system, where strain signals
      were extracted well below the noise floor normally imposed by the frequency
      fluctuations of the laser. Initial measurements show a reduction in the noise
      floor by a factor of 30, with strain sensitivities of a nanostrain/Hz at 100 mHz
      and reaching 100 ps/Hz at 1 Hz. Further characterization of the system indicates
      the potential for at least 4.5 orders of magnitude frequency fluctuation
      rejection.

PMID- 22660158
TI  - Identification of volatile lung cancer markers by gas chromatography-mass
      spectrometry: comparison with discrimination by canines.
AB  - In this work, a chromatographic method for identification of volatile organic
      compounds was compared with canine recognition. Gas chromatography and mass
      spectrometry (GC-TOF MS) were used for determination of concentrations of trace
      gases present in human breath. The technique enables rapid determination of
      compounds in human breath, at the parts per billion level. Linear correlations
      were from 0.83-234.05 ppb, the limit of detection was the range 0.31-0.75 ppb,
      and precision, expressed as relative standard deviation (RSD), was less than
      10.00 %. Moreover, trained dogs are able to discriminate breath samples of
      patients with diagnosed cancer. We found a positive correlation between dog
      indications and the ethyl acetate and 2-pentanone content of breath (r = 0.85 and
      r = 0.97, respectively). The methods presented for detection of lung cancer
      markers in exhaled air could be used as a potential non-invasive tool for
      screening. In addition, the canine method is relatively simple and inexpensive in
      comparison with chromatography.

PMID- 22660168
TI  - Spreading of Alzheimer's disease inflammatory signaling through soluble micro
      RNA.
AB  - Alzheimer's disease is a progressive, neurodegenerative disorder that develops
      within the limbic system, spreading radially into anatomically linked brain
      association areas as the disease progresses. Analysis of temporal-lobe
      association of neocortex-derived extracellular fluid and cerebrospinal fluid from
      Alzheimer's disease patients shows an abundant presence of micro-RNA (miRNA),
      including the proinflammatory miRNA-146a and miRNA-155. Using a novel and highly
      sensitive LED-Northern dot-blot focusing technique, we detected the secretion of
      potentially pathogenic amounts of miRNA-146a and miRNA-155 from stressed human
      primary neural cells. A conditioned medium containing miRNA-146a and miRNA-155
      was found to induce Alzheimer-type gene expression changes in control brain
      cells. These included downregulation in the expression of an important repressor
      of the innate immune response, complement factor H (CFH). These effects were
      neutralized using anti-miRNA strategies. Anti-miRNA-based therapeutics may
      provide a novel and efficacious treatment to stem the miRNA-mediated spreading of
      inflammatory signaling involved in Alzheimer's disease.

PMID- 22660169
TI  - Math5 (Atoh7) gene dosage limits retinal ganglion cell genesis.
AB  - The basic helix-loop-helix factor Math5 (Atoh7) is critical for the determination
      of retinal ganglion cell (RGC) fate in mice. Recently, genome-wide association
      studies have identified the ATOH7 locus as a major determinant of variation in
      the human optic disc area, which is directly correlated with the RGC number.
      These studies suggest that the level of Math5 expression may determine the
      ultimate number of RGCs. To test this hypothesis, we systematically compared
      optic nerve area and RGC axon number in C57BL/6J congenic Math5+/- and +/+ mice
      at young adult and neonatal ages by transmission electron microscopy. Optic disc
      area and RGC abundance were not significantly different in adults, but
      heterozygotes had thinner optic nerves and 25-30% fewer RGCs at birth than wild
      type littermates (P<0.05). Our results suggest that Math5 dosage is important for
      the genesis, but not the ultimate number, of RGCs. Our findings highlight the
      importance of ganglion cell culling as a compensatory mechanism for retinal
      homeostasis, and support a quantitative role for Math5 in RGC specification.

PMID- 22660171
TI  - Blocking the interleukin 2 (IL2)-induced systemic autophagic syndrome promotes
      profound antitumor effects and limits toxicity.
AB  - Cancer is the leading cause of death in the United States in those dying under
      the age of 85. Although cancer is increasingly controlled as a chronic disease,
      true cures of patients with metastatic epithelial malignancies have rarely been
      obtained with currently available systemic therapies. For example, administration
      of high-dose recombinant interleukin 2 (IL2), enhancing cytolytic immune cell
      proliferation and delivery, promotes complete antitumor responses in < 10% of
      treated individuals. Means to reduce the toxicity, attributed to a cytokine storm
      and an associated "systemic autophagic syndrome" as well as enhance efficacy and
      increase the potential set of malignancies in which it is applied (currently
      patients with renal cancer and melanoma) would be of great interest. IL2 promotes
      both T-cell and NK cell induction of immune cell-mediated autophagy (iC-MA) in
      tumor targets. We have demonstrated that HMGB1 is detected at high levels in the
      serum of IL2-treated mice with translocation to the cytoplasm from the nucleus in
      the liver, consistent with HMGB1's release in response to stress, and ability to
      sustain autophagy. Limiting autophagy in mice with coadministration of
      chloroquine (CQ) diminishes serum levels of HMGB1, cytokines (IFNG and IL6 but
      not IL18), and autophagic flux, attenuating weight gain, enhancing DC, T-cell and
      NK cell numbers, and promoting long-term tumor control in a murine hepatic
      metastases model. Autophagy (programmed cell survival) is a metabolic process
      associated with promotion of late cancer growth. In tumor cell lines, CQ
      treatment limits ATP production through inhibition of oxidative phosphorylation
      and promotion of apoptosis. CQ increases autophagic vacuoles and LC3-II levels in
      tumor cells, associated with increased annexin V(+)/PI(-) cells, cleaved-PARP,
      cleaved-CASP3, and cytochrome c release from mitochondria. These observations,
      limiting toxicity and prolonging antitumor effects, with a combination of IL2 and
      autophagy inhibition in murine models are now being tested by the Cytokine
      Working Group in patients with advanced renal cell carcinoma.

PMID- 22660186
TI  - A microRNA signature specific for hairy cell leukemia and associated with
      modulation of the MAPK-JNK pathways.

PMID- 22660185
TI  - Bone cell interactions through Eph/ephrin: bone modeling, remodeling and
      associated diseases.
AB  - Bones cannot properly form or be maintained without cell-cell interactions
      through ephrin ligands and Eph receptors. Cell culture analysis and evaluation of
      genetic mouse models and human diseases reveal various ephrins and Eph functions
      in the skeletal system. Migration, attachment and spreading of mesenchymal stem
      cells are regulated by ephrinB ligands and EphB receptors. ephrinB1 loss-of
      function is associated with craniofrontonasal syndrome (CFNS) in humans and mice.
      In bone remodeling, ephrinB2 is postulated to act as a "coupling stimulator." In
      that case, bidirectional signaling between osteoclastic ephrinB2 and osteoblastic
      EphB4 suppresses osteoclastic bone resorption and enhances osteoblastic bone
      formation, facilitating the transition between these two states. Parathyroid
      hormone (PTH) induces ephrinB2 in osteoblasts and enhances osteoblastic bone
      formation. In contrast to ephrinB2, ephrinA2 acts as a "coupling inhibitor,"
      since ephrinA2 reverse signaling into osteoclasts enhances osteoclastogenesis and
      EphA2 forward signaling into osteoblasts suppresses osteoblastic bone formation
      and mineralization. Furthermore, ephrins and Ephs likely modulate pathological
      conditions such as osteoarthritis, rheumatoid arthritis, multiple myeloma and
      osteosarcoma. This review focuses on ephrin/Eph-mediated cell-cell interactions
      in bone biology.

PMID- 22660187
TI  - The novel tribody [(CD20)(2)xCD16] efficiently triggers effector cell-mediated
      lysis of malignant B cells.
AB  - Bispecific antibodies (bsab) offer a promising approach for optimizing antibody
      based therapies. In the present study, [(CD20)(2)xCD16], a recombinant CD20- and
      CD16-directed bsab in the tribody format, was designed to optimize recruitment of
      FcgammaRIII (CD16)-positive effector cells. [(CD20)(2)xCD16] retained the antigen
      specificities of the parental monoclonal antibodies and binding to FcgammaRIIIa
      was not compromised by the F/V polymorphism at amino-acid position 158.
      [(CD20)(2)xCD16] mediated potent lysis of lymphoma cell lines and freshly
      isolated tumor cells from patients, even at low picomolar concentrations (~10
      pM). Irrespective of the CD16a allotype, potency as well as efficacy of lysis
      obtained with the tribody was significantly higher than lysis triggered by
      rituximab. Tumor cell killing also occurred when autologous NK cells were used as
      effector cells. Compared with rituximab, the tribody demonstrated depletion of
      autologous B cells in ex vivo whole blood assays at 100-fold lower antibody
      concentration. In mice with a reconstituted humanized hematopoietic system,
      established by transplantation of human CD34-positive cord blood cells, this
      novel tribody significantly depleted autologous human B cells. Thus, tribodies
      such as [(CD20)(2)xCD16], recruiting CD16-positive effector cells, may represent
      promising candidates for clinical development.

PMID- 22660188
TI  - Genetic polymorphisms and childhood acute lymphoblastic leukemia: GWAS of the
      ESCALE study (SFCE).

PMID- 22660203
TI  - Comparison of functional fibrinogen assessment using thromboelastography with the
      standard von Clauss method.
AB  - AIM: To compare assessment of fibrinogen by thromboelastography with the standard
      von Clauss method. METHODS: Observational prospective study. RESULTS:
      Thromboelastography provides direct and complex evaluation of the entire
      coagulation cascade based upon changes in blood viscosity. It affects both
      platelets and plasma components. New application of this method measures
      fibrinogen contribution to coagulation as opposed to fibrinogen antigen levels
      measured by immunoassay. Paired samples from 117 patients before cardiopulmonary
      bypass were compared. A moderate correlation was found between fibrinogen and
      functional fibrinogen with a Spearman correlation coefficient of 0.476.
      CONCLUSION: The functional fibrinogen test is a valid point-of-care method for
      fibrinogen assay with a moderate correlation to the standard method.

PMID- 22660204
TI  - The needs of mothers to newborns hospitalised in intensive care units.
AB  - OBJECTIVE: The aim of the survey was to identify the needs of mothers to infants
      hospitalized in intensive care units (ICUs) and second, to assess the level of
      parental support provided by the health personnel. METHODS: The sample consisted
      of 147 mothers to infants hospitalized in ICUs. The research was conducted over
      six months in ICUs for newborns at two hospitals in Ostrava. The study used two
      standardized questionnaires: The parental stressor questionnaire scale: Neonatal
      Intensive Care Unit which measures the degree of stress in parents of
      hospitalized infants and the questionnaire The Nurse Parent Support Tool which
      evaluates the level of parental support provided by nursing staff. RESULTS: The
      highest level of stress was identified in the parental role. Specifically, the
      inability to help the child remain separate from the mother, a feeling of
      helplessness and inability to protect the child from painful procedures and the
      inability to feed her baby. Mothers evaluated the support of nursing staff in
      most of these areas as high. Top were rated the ability of the caring staff to
      respond well to the questions of parents and the mother's willingness to engage
      in childcare. CONCLUSION: Intensive care units for the newborn obviously need to
      be family-centered care and at the same time they must be aware of all the
      factors that can be sources of stress for the parents.Only in this way can stress
      be eliminated with positive impact on the relationship between mother and child.

PMID- 22660205
TI  - The value of 18F-FDG PET/CT in assessment of metabolic response in esophageal
      cancer for prediction of histopathological response and survival after
      preoperative chemoradiotherapy.
AB  - AIM: To evaluate the ability of hybrid 18F-fluorodeoxyglucose positron emission
      tomography/computed tomography ((18)F-FDG PET/CT) to predict histopathological
      response and overall survival (OS) after preoperative neoadjuvant
      chemoradiotherapy (CRT) in patients with the esophageal carcinoma. METHODS: 73
      patients with locally advanced esophageal carcinoma were included in the study.
      All were treated with CRT and 34 subsequently underwent surgical resection of the
      esophagus. (18)F-FDG PET/CT was carried out prior to (PET/ CT1) and 6 weeks after
      (PET/CT2) completion of the CRT. RESULTS: PET/CT2-determined complete metabolic
      response (CMR) was achieved in 6 (17.6%) out of 34 operated patients, the
      metabolic response was incomplete (NCMR) in 28 (82.4%) patients. A
      histopathological complete response (CR) to CRT was discovered in 7 patients
      (20.6%). The median OS in operated patients was 17.1 months, 95% CI:12.9-23.3
      months. In a group of 39 non-operated patients, CMR after neoadjuvant CRT was
      achieved in 12 patients (30.8%), while NCMR was found in 28 (82.4%). The median
      OS was 13.5 months in this group, 95% CI: 4.4-22.7 months. CONCLUSION: No
      statistically significant correlation was found between the (18)F-FDG metabolic
      response after the neoadjuvant CRT and histopathological response. Presently, the
      contribution of (18)F-FDG PET/CT as a marker of the potential result of CRT
      cannot be considered definite. Another study with a larger sample of patients and
      standardized algorithms for the examining protocols would be necessary for
      reaching definitive conclusions.

PMID- 22660206
TI  - Comparison of three screening tools for nutritional status assessment of the
      elderly in their homes.
AB  - BACKGROUND: The prevailing recommendation for the elderly is to live in their own
      homes as long as conditions allow. With this emphasis on the natural living
      environment, it is imperative to closely monitor both the general health and
      nutritional needs of the elderly in community settings. AIM: The aim of the study
      was to compare three nutritional status screening and evaluation tools of the
      elderly in their homes. METHODS: Testing of measuring instruments, MNA, SGA, and
      MUST took place in the homes of 120 seniors in selected areas of the Czech and
      Slovak Republics. The study included 120 seniors. For testing of the
      relationships and dependencies, Pearson's correlation coefficient, t and Fisher
      tests were used. The level of statistical significance was alpha = 0.05. RESULTS:
      All tests were to a large degree correlated (p(MNA) = 0.0049; p(MUST) = -0.537;
      p(SGA) = -0.578) with the body mass index of the seniors. Simultaneously, it was
      confirmed that the tools for assessing nutritional status in the study showed
      significant differences regarding the classification of patients at risk of
      malnutrition and/or malnourished patients. CONCLUSIONS: Based on the findings, we
      conclude that MNA appeared to be a more appropriate tool for nutritional
      assessment of the elderly living in their homes. SGA and MUST provided rather
      subjective evaluation of the nutritional status and did not furnish an in-depth
      categorization of malnutrition.

PMID- 22660207
TI  - Comparison of the quality of lower limb magnetic resonance angiographies
      performed with different paramagnetic contrast agents in relation to body mass
      index and ejection fraction.
AB  - AIM: To compare the quality of magnetic resonance angiographies (MRAs) performed
      with different contrast agents and to evaluate the effect of body mass index
      (BMI) and ejection fraction (EF) on the quality of these MRAs. MATERIALS AND
      METHODS: 120 patients between the age of 43 and 86 years were subjected to MRAs
      with different contrast agents (Gadobutrolum, Dimeglumini gadobenas, Gadofosveset
      trisodium). Each patient's BMI was calculated, and EF was established using MR
      examination of the heart. Objective evaluations of the quality of the MRAs were
      done using abdominal fat-to-aorta enhancement ratio (FAR) comparisons. This ratio
      was then correlated with the patient's BMI and EF. Subjective evaluations of the
      quality of the MRAs were done by 5 blinded evaluators. Correlation analysis and
      analysis of variance were used for statistical assessement. RESULTS: There was no
      statistically significant difference in FAR for any of the contrast agent groups.
      There was a mesoscale correlation between a patient's BMI and FAR. However, no
      correlation was found between the EF and FAR for any of the contrast agent
      groups. The results of the subjective evaluation showed that there was no
      statistical difference in the quality of MRAs regardless of the contrast agent
      used. CONCLUSION: Subjectively there was no statistically significant difference
      in the quality of the MRAs. Irrespective of the type of contrast used or the
      patient's EF, the lower the BMI of a patient the higher the signal enhancement
      and hence the better the quality of the MRA produced in that patient.

PMID- 22660208
TI  - Radiofrequency upper thoracic sympathectomy in the treatment of critical upper
      limb ischemia--a case series.
AB  - BACKGROUND: Patients with significant medical and social problems resulting from
      impaired perfusion of the upper limbs caused by micro- or macro-angiopathy are
      now frequent in clinical practice. Vasospastic disease of the upper limbs of
      combined origin is a difficult condition to treat by conservative methods and
      therapeutic strategies are usually multidisciplinary. In addition to standard
      pharmacotherapy, treatment may involve regional anaesthesia, thoracoscopic or
      radiofrequency sympathectomy and surgical treatment of defects, including plastic
      surgery. METHODS: This paper describes our successful work in the treatment of
      upper limb critical ischemia using radiofrequency upper thoracic sympathectomy.
      RESULTS: In three case reports we present the results of radiofrequency
      thermolysis applied to treat patients with chronic defects of the hand and
      fingers. These patients were diagnosed with upper limb critical ischemia of
      combined origin, standard conservative treatment methods failed and surgical
      intervention was originally not indicated, however, radiofrequency thermolysis
      proved to be beneficial. CONCLUSIONS: Radiofrequency thoracic sympathectomy could
      improve peripheral perfusion of the upper limbs and thereby contribute to healing
      of chronic defects, reduction of pain and improvement in the quality of life of
      the patients.

PMID- 22660209
TI  - A significant proportion of patients with chronic myeloid leukemia and suboptimal
      response according to European Leukemia Net criteria have excellent prognosis
      without treatment change.
AB  - BACKGROUND: The Recommendations of the European Leukemia Net (ELN) have become an
      essential tool in the management and prognosis of patients with chronic myeloid
      leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). However, the
      definition of suboptimal response remains under discussion. METHODS: We used
      conventional cytogenetics for the detection of clonal changes in Ph-positive and
      negative clones. RT-PCR and sequencing were carried out on peripheral blood
      leukocytes to detect the type of BCR-ABL1 transcript. The BCR-ABL1 mutational
      status was assessed using sequencing of RT-PCR products. High performance
      capillary electrophoresis for determination of imatinib (IMA) plasma
      concentration was used. RESULTS: A retrospective study of 110 patients diagnosed
      with chronic-phase (CP) CML treated with IMA or 2(nd) generation TKIs in the
      years 2000-2009 focused on analysis of patients with suboptimal response
      according to ELN criteria. 40 patients were administered IMA as first-line
      therapy and 70 had been pretreated with interferon-alpha (IFN-alpha) with or
      without Ara-C and/or hydroxyurea (HU) for a median 12 months (range, 1-92
      months). After adjusting for the ELN criteria, major molecular response (MMR) was
      achieved after median 34 and 39 months in 66.7% and 41.7% of patients after the
      first and second-line IMA therapy with suboptimal response defined as lack of
      achievement of MMR at the 18(th) month of treatment, respectively. In comparison
      to patients with optimal response, patients with suboptimal response did not show
      significant differences in overall survival (OS) or progression-free survival
      (PFS). Cytogenetic assays demonstrated additional chromosome abnormalities
      (ACAs): chromosome 8 trisomy in a Ph-negative clone during the IMA treatment (in
      1 case) and der(9q) in Ph-positive clone (in 2 cases); in patients receiving
      first-line IMA only chromosome 8 trisomy was observed which was associated with
      myelodysplastic syndrome - this was the only case where hematopoietic stem cell
      transplantation (HSCT) was performed. During the treatment with IMA in both
      subgroups no regulatory mutations in the ABL kinase domain were confirmed.
      CONCLUSION: We believe that the category of suboptimal response should be
      redefined or withdrawn from the ELN 2009 recommendations for management of CML
      patients treated with TKIs. Patients with suboptimal response who have no
      additional risks (additional cytogenetic abnormalities or BCR-ABL1 regulatory
      mutations) may remain on IMA treatment while patients with these risks should be
      switched to the 2(nd) generation TKIs.

PMID- 22660210
TI  - The role of adrenomedullin and galanin in recurrent vasovagal syncope: a case
      control study.
AB  - AIMS: Orthostatic stimuli are known to elicit changes in vasoactive peptide
      levels. The hypothesis of no difference in adrenomedullin and/or galanin levels
      in patients with recurrent vasovagal syncope and healthy controls was tested in a
      passive 35-min head-up tilt test (HUTT). METHODS: Twenty eight persons (14
      patients and 14 healthy controls) were tested in a 35-min/60 degrees  head-up
      tilt test with telemetry monitoring. Three blood samples were evaluated for each
      person during the HUTT. Plasma levels of adrenomedullin and galanin were analysed
      by the Kruskal-Wallis test for all sampling periods. Vagal influence was
      indirectly assessed by the break index. RESULTS: There were no significant
      differences between groups in median values for either adrenomedullin or galanin
      plasma levels (all 6 p-values were greater than 0.4). For adrenomedullin, no
      significant difference between groups was found. For galanin, the rate of change
      between the 1st and 2nd measurement was significantly greater for patients
      (P=0.04), regardless of HUTT result but between the 2(nd) and 3(rd) measurement
      it was insignificant (P=0.36). In the group of positive cases, the break index
      increased significantly (P=0.02). CONCLUSION: We confirmed that there is a
      different galanin secretion pattern during orthostatic provocation in patients
      with recurrent vasovagal syncope than healthy individuals. For adrenomedullin, no
      significant difference was found. A significant increment of the break index
      confirmed increased vagal influence in the subgroup of positive cases.

PMID- 22660211
TI  - Optimizing the pacing site in the ventricular septum by fluoroscopy and
      morphology of the paced QRS complex.
AB  - AIMS: To analyze the paced QRS duration in various septal positions of the right
      ventricular leads and with different paced QRS vectors. To use the results to
      assess parameters suggesting the optimal site for right ventricular pacing.
      METHODS AND RESULTS: A total of 609 patients with leads implanted in the right
      ventricular septum were classified using fluoroscopy in the lateral view (the
      primary pacing site), and in the anteroposterior view (the secondary pacing
      site), according to the QRS vector in leads I and III. Significantly shortened
      paced QRS was found in the primary pacing site with the true septal compared with
      the anteroseptal site, with the vector being negative or isoelectric in lead I
      plus positive in lead III. In secondary pacing sites, no significant difference
      in pacing QRS duration was found between RVOT-HS, RVOT-LS, mid-septum and
      inferior-septum. CONCLUSIONS: For optimization of the pacing site in the
      ventricular septum, the following are significant: the primary site based on the
      lateral view, and the paced QRS vector in leads I and III.

PMID- 22660212
TI  - Surgical complications of the anterior approach to the L5/S1 intervertebral disc.
AB  - AIM: The aims of this study were to describe the incidence and type of
      perioperative complications that occur with minimally invasive anterior
      retroperitoneal spinal surgery performed at the level of the L5/S1 intervertebral
      disc. METHODS: A retrospective review of 175 patients: 103 women and 72 men,
      average age 45, who had undergone anterior spinal surgery at level L5/S1 from
      January 2001 to February 2011. The preoperative diagnoses were: degenerative disc
      disease in 87 (50%), failed back surgery syndrome in 53 (30%) and
      spondylolisthesis in 35 patients (20%). The surgical steps in the minimally
      invasive anterior retroperitoneal approach from the right side to disc L5/S1 are
      described. All surgical intraoperative anatomical anomalies and complications
      directly related to the anterior spinal surgery were documented. RESULTS:
      Intraoperative pathological-anatomical anomalies were found in 34 patients (19%)
      and intra - and postoperative minor complications in 24 patients (12%) but no
      serious complications. The main intraoperative complication was peritoneal
      opening without visceral injury (5%) and the main postoperative complication was
      weakness of the right abdominal wall (3%). CONCLUSION: . Retroperitoneal access
      and surgery at level L5/S1 disc space is a safe procedure when performed by a
      knowledgeable and experienced spine team. During surgical planning for an
      anterior approach to the LS spine, the surgeon must carefully assess the
      neuroimaging results, such as MRI, to minimize potentially disastrous vascular
      complications.

PMID- 22660213
TI  - Topotecan vitreous and plasma levels and retinal toxicity after transcorneal
      intravitreal delivery in healthy albino rabbits: alternative retinoblastoma
      treatment.
AB  - AIM: To determine intravitreal and plasma concentrations and retinal toxicity
      after transcorneal intravitreal injection of 1 MUg and 2 MUg of topotecan
      (Hycamtin). METHOD: Twelve healthy albino rabbits were included in this in vivo
      experiment. Six anesthetized albino rabbits received a single transcorneal
      intravitreal injection of 1 MUg (group A) or 2 MUg (group B) of topotecan.
      Vitreous and blood samples were collected until 168 h. Left eyes were treated
      with the same volume of saline. Plasma and vitreous levels of topotecan were
      determined by high-performance liquid chromatography. Area under the plasma
      concentration time curve (AUC) was calculated using trapezoidal rule. Clinical
      evidence of toxicity was classified into four grades according to anatomical
      structures. Electroretinograms (ERGs) were recorded. RESULTS: Time to maximum
      concentration was observed up to 2 h after drug injection in group A whereas up
      to 1 h in group B. Low levels of topotecan were detected in plasma in both groups
      and in the vitreous humor of the contralateral eye in group B. Topotecan levels
      (mean vitreous AUC in group A 2.55 MUg/mL.h and in group B 5.338 MUg/mL.h) were
      detectable up to 6 h in both groups. We observed following structural changes in
      rabbit eyes: corneal vascularization, cataract, hemophthalmus, choroidal edema
      and focal retinal atrophy. Abnormal ERGs were obtained. CONCLUSION: Our findings
      proved that transcorneal intravitreal administration of 1 MUg and 2 MUg of
      topotecan results in potentially cytotoxic intraocular concentrations. More
      studies are needed to establish the safety of topotecan for retinoblastoma in
      children.

PMID- 22660214
TI  - MR enterography with a new negative oral contrast solution containing maghemite
      nanoparticles.
AB  - AIM: The aim of this study was to test an oral contrast solution with maghemite
      for the magnetic resonance imaging of small bowel diseases. PATIENTS AND METHODS:
      The study sample included 3 cohorts: 17 healthy volunteers (group A), 22 patients
      with small bowel disease (group C). Both groups underwent MR enterography and 24
      patients with small bowel disease (group B) underwent magnetic resonance
      cholecystopancreaticography. Various concentrations in 1000 ml vs 500 ml of
      experimental solution were tested. All cohorts completed questionnaires
      evaluating the solution characteristics and side-efects during and after
      drinking. RESULTS: A maghemite concentration of 800 mg /4 g bentonite in 1000 ml
      solution was sufficient for proper intraluminal lay-out. An experimental solution
      of 500 ml was sufficient for magnetic resonance cholecystopancreaticography and
      1000 ml for MR enterography. There were no statistically significant differences
      between groups for taste, taste characteristic or appearance of the experimental
      solution. Side-effects experienced during drinking were: nausea (29.4%) and
      eructation (29.4%) in group A, in group B (42%) and diarrhoea (27.3%) in group C.
      Side-effects 2 h after drinking occured in group A (nausea 17.6%) and in group C
      (diarrhoea 47%). The best tolerance of experimental solution was found in group B
      with a higher median patient age than groups A and C. The experimental solution
      was evaluated more favorably in the older subjects (age over 50 years).
      CONCLUSION: The experimental oral solution with maghemite was well tolerated in
      all 3 groups. Our study supports its use in magnetic resonance practice.

PMID- 22660215
TI  - Glibenclamide-pregnenolone derivative has greater hypoglycemic effects and
      biodistribution than glibenclamide-OH in alloxan-rats.
AB  - AIM: The present study was designed to investigate the activity of two
      glibenclamide derivatives on glucose concentration. An additional aim was to
      identify the biodistribution of glibenclamide derivatives in different organs in
      a diabetic animal model. METHODS: The effects of two glibenclamide derivatives on
      glucose concentration were evaluated in a diabetic animal model. In addition,
      glibenclamide derivatives were bound to Tc-99m using radioimmunoassay methods. To
      evaluate the pharmacokinetics of the glibenclamide derivatives over time (15, 30,
      45 and 60 min) the Tc-99m-glibenclamide conjugates were used. RESULTS: The
      results showed that glibenclamide-pregnenolone had greater hypoglycemic activity
      than glibenclamide or glibenclamide-OH. The data also showed that the
      biodistribution of Tc-99m-glibenclamide-OH in all organs was less than that of
      the Tc-99m-glibenclamide-pregnenolone derivative. CONCLUSIONS: The glibenclamide
      pregnenolone derivative had greater hypoglycemic effects and its biodistribution
      was wider than glibenclamide-OH. The data suggest that the steroid nucleus may be
      important to the hypoglycemic activity of the glibenclamide-pregnenolone
      derivative and this could be related to the degree of lipophilicity induced by
      the steroid nucleus in the chemical structure of glibenclamide-pregnenolone.

PMID- 22660216
TI  - Hemodynamic responses and serum nitrite concentration during uncontrolled
      hemorrhagic shock in normotensive and hypertensive rats.
AB  - BACKGROUND: We evaluated the effect of hypertension on hemodynamic responses and
      serum nitrite concentrations in normotensive (NT) and deoxycorticosteron acetate
      (DOCA)-Salt hypertensive (HT) rats. METHODS: Uncontrolled hemorrhagic shock was
      induced in NT and HT rats (n=7 each) by preliminary bleed of 25 ml/kg followed by
      a 75% tail amputation. The mean arterial pressure (MAP), heart rate and serum
      nitrite were measured pre-hemorrhage and during hemorrhage. RESULTS: Changes in
      time-averaged MAP after hemorrhage were significantly greater in HT group than
      NT. After resuscitation, the HT rats failed to restore MAP to baseline level.
      Serum nitrite level in both groups was significantly increased during shock
      period. Survival rate of HT animals was lower than NT group, although it was not
      statistically significant. CONCLUSIONS: Marked reduction of MAP and less
      improvement after resuscitation suggested the less adaptation of cardiovascular
      system in HT animals which may interfere with management of these subjects during
      uncontrolled hemorrhagic shock.

PMID- 22660217
TI  - Association of STAT6 and ADAM33 single nucleotide polymorphisms with asthma
      bronchiale and IgE level and its possible epigenetic background.
AB  - BACKGROUND: ADAM33 and STAT6 belong to the candidate genes that have been
      commonly associated with asthma, bronchial hyperresponsiveness or IgE levels. Our
      objective was to assess the association of 11 SNPs of the ADAM33 and 6 of the
      STAT6 and their haplotypes with IgE levels and asthma. We also evaluated the
      possible role of parental origin of haplotypes on IgE levels. METHODS: We
      enrolled 109 children with asthma and 45 healthy controls. Genotyping was
      performed by TaqMan probes and confirmed by sequencing. Haplotype construction
      was based on the knowledge of parental genotypes and also inferred by using the
      EM algorithm and Bayes' theorem. RESULTS: None of the SNPs were associated with
      elevated IgE level or asthma. We found that the most frequent STAT6 haplotype
      ATTCAA (built from rs324012, rs324011, rs841718, rs3024974, rs3024974, rs4559
      SNPs, respectively) was associated with elevated total IgE levels (P=0.01) and
      this haplotype was predominantly transmitted paternally (P<0.001). We compared
      our results with those of studies performed on German and Australian Caucasian
      populations and found that rs324011, rs3024974 and rs4559 SNPs in STAT6 should
      have a major effect on IgE levels. Therefore, we suggest the TCA haplotype alone
      (built from rs324011, rs3024974 and rs4559 SNPs, respectively) in STAT6 is
      associated with total IgE elevation. CONCLUSIONS: The influence of paternal
      origin of the STAT6 haplotype on IgE levels is surprising but the exact role of
      possible paternal imprinting in STAT6 regulation should be investigated and
      confirmed in future studies.

PMID- 22660218
TI  - Risk factors associated with ischemic heart disease occurence in acute ischemic
      stroke patients.
AB  - AIMS: At specific time periods following ischemic stroke (IS), acute coronary
      syndrome as ischemic heart disease (IHD) represents a higher risk of death than
      IS. Not all IS patients can undergo specific examination for IHD detection. The
      aim of this study was to assess exclusive risk factors (RFs) associated with IHD
      occurrence in IS patients. Knowledge of these RFs should help in stratifying IS
      patients for IHD detection. MATERIALS AND METHODS: This was a hospital-based,
      retrospective, single centre study. The sample consisted of 192 consecutive IS
      patients, divided into two subgroups - Subgroup 1 (54 patients without IHD; 55.6%
      males; 63.1 +/- 11.8 years) and Subgroup 2 (138 patients with IHD; 39.1% males;
      76.3 +/- 9.6 years). The following factors were identified: age; sex; presence of
      arterial hypertension, atrial fibrillation, diabetes mellitus; plasma levels of
      total cholesterol, triglycerides, low-density cholesterol, high-density
      cholesterol; body mass index; presence of carotid plaques. Logistic regression
      analysis was used for statistical evaluation. RESULTS: Of all identified risk
      factors only age (OR=1.109; 95% CI: 1.069 - 1.150, P=0.001) and the presence of
      arterial hypertension (OR=6.298; 95% CI: 2.215 - 17.905, P=0.003) were
      exclusively and significantly associated with the presence of IHD in IS patients.
      CONCLUSIONS: Age and arterial hypertension may be exclusive risk factors
      associated with IHD in IS patients.

PMID- 22660219
TI  - Real time 3-dimensional transesophageal echocardiography is more specific than 2
      dimensional TEE in the assessment of left atrial appendage thrombosis.
AB  - BACKGROUND: In patients indicated for detection of intraatrial thrombus (T), 2
      dimensional transesophageal echocardiography (2DTEE) is routinely used but
      differentiation between T and trabeculae or artifacts in the left atrial
      appendage (LAA) is often difficult. AIMS: To compare the diagnostic value of real
      time 3D-transesophageal echocardiography (RT3DTEE) and 2DTEE in the assessment of
      LAA thrombosis. PATIENTS AND METHODS: One hundred and ten consecutive patients
      (73M, aged 64+-13) were examined by 2DTEE. In terms of possible T, individual pts
      were diagnosed as negative (N2), uncertain trabecular finding (U2),
      other/artifacts (O2), and clearly positive (T2). The RT3DTEE was then applied and
      the categorization repeated (N3,U3,O3 and T3, resp.). Finally, the operator
      decided whether the RT3DTEE. A: had an additional diagnostic value, and/or B:
      changed the definite diagnosis of thrombosis. RESULTS: N2:71; U2:17; O2:19; T2:3;
      N3:97; U3:1; O3:12; T3:0. Ad A/ RT3DTEE enabled us to refine or change the
      diagnosis in 26/110 cases. 17 pts were switched from group U2 to N3, 7:O2-N3 and
      2:T2-N3. 12 pts from O2 and 1 pt from T2 remained unclarified. Ad B/ Diagnoses
      were changed in 6 patients after RT3DTEE. A very suspicious T2 was found in 3
      patients. In 1, the finding was requalified definitely as musculi pectinati. In
      the second patient, the finding was re-categorized as just a spontaneous
      echocontrast without T. In another 4 patients, T in LAA was definitely excluded
      after RT3DTEE (1 patient switched from U2 to N3, 3 from O2 to N3). In another 13,
      the findings remained unclear, mostly because of poor quality image. No real
      thrombus was found in this study. CONCLUSION: RT3DTEE provides additional
      information, which may be helpful in the differentiation of thrombus from other
      findings. It is particularly useful in the identification of muscular trabeculae
      in the left atrial appendage.

PMID- 22660220
TI  - Genetic polymorphism of drug metabolizing enzymes (GSTM1 and CYP1A1) as risk
      factors for oral premalignant lesions and oral cancer.
AB  - AIMS: Polymorphisms in the genes that code for metabolic enzymes involved in
      either the activation (Phase I) or detoxication (Phase II) of chemical
      carcinogens in tobacco, may alter expression or function of carcinogenic
      compounds and hence alter risk of oral cancer. The present study investigates
      whether polymorphisms at CYP1A1 and GSTM1 gene loci act as risk factors for oral
      precancerous lesions and cancer. METHODS: For the present study,
      histopathologically confirmed cases of 90 oral precancerous lesions, 150 oral
      squamous cell carcinoma (SCC) and 150 control subjects were selected. Polymerase
      chain reaction and restriction fragment length polymorphism were performed using
      DNA from blood samples to determine the polymorphic genotypes at CYP1A1 and GSTM1
      loci. RESULTS: CYP1A1 C (m2/m2) genotype conferred a 12.0 fold-increased risk
      (OR=12.0; 95% CI, 2.40-60.05) to oral SCC. GSTM1 null showed no significant
      association but the frequency was higher in oral SCC cases. Patients with
      genotype C and/or GSTM1 deficiency developed carcinoma after less tobacco
      consumption than those of other genotypes though the difference was not
      statistically significant. The frequency of the combined genotypes C and GSTM1
      null was found to be 14% among oral SCC patients. On comparing the susceptibility
      of intraoral sites it was found that in the majority of cases (64%) in the study
      groups they were the buccal mucosa. CONCLUSION: Hence it was concluded that
      metabolic enzymes reported in the present study: CYP1A1 significantly alter oral
      cancer risk. GSTM1 null and CYP1A1 C (m2m2) show a predisposition to premalignant
      lesions and cancer of the buccal mucosa than other sites.

PMID- 22660221
TI  - Effect of progesterone-carbachol derivative on perfusion pressure and coronary
      resistance in isolated rat heart: via activation of the M2 muscarinic receptor.
AB  - AIM: The present study was designed to investigate the effects of progesterone
      carbachol derivative on perfusion pressure and coronary resistance in rats. An
      additional aim was to identify the molecular mechanisms involved. METHODS: The
      Langendorff model was used to measure perfusion pressure and coronary resistance
      changes in isolated rat heart after progesterone-carbachol derivative alone and
      after the following compounds; mifepristone (progesterone receptor blocker),
      yohimbine (alpha2 adreno-receptor antagonist), ICI 118,551 (selective beta2
      receptor blocker), atropine (non-selective muscarinic receptor antagonist),
      methoctramine (antagonist of M2 receptor) and L-NAME (inhibitor of nitric oxide
      synthase). RESULTS: The results show that progesterone-carbachol derivative [10(
      9) mM] significantly decreased perfusion pressure (P=0.005) and coronary
      resistance (P=0.006) in isolated rat heart. Additionally, the effect of
      progesterone-carbachol on perfusion pressure [10(-9) to 10(-4) mM] was only
      blocked in the presence of methoctramine and L-NAME. CONCLUSIONS: These data
      suggest that progesterone derivative exert its effect on perfusion pressure via
      activation of the M2 muscarinic. In addition, this phenomenon involves
      stimulation of nitric oxide synthase (NOS).

PMID- 22660222
TI  - Esophagectomy for esophageal carcinoma--surgical complications and treatment.
AB  - AIM: To describe our experience with esophagectomy for esophageal cancer and, the
      development and treatment of complications arising from the surgery. MATERIAL AND
      METHODS: From 2007 to 8/2010, esophagectomy for esophageal carcinoma was
      performed in 75 patients at the 1(st) Surgical Clinic. Primary esophagectomy was
      indicated in 20 patients with T1N0 stage or in cases where neoadjuvant treatment
      was contraindicated. 55 patients with T2,3N0,1 stages received neoadjuvant
      radiochemotherapy. Esophagectomy was performed via an abdominal approach
      (transhiatal laparoscopy in 44 patients, laparotomy in 3 patients) and a thoracic
      approach (thoracoscopy in 10 patients, thoracotomy in 18 patients). RESULTS: In
      18 cases, one or both pleural cavities were opened by means of dissection of the
      mediastinal pleura during the transhiatal laparoscopic esophagectomy. The
      morbidity was 26.6% and the following complications were encountered: pulmonary
      (15 patients), anastomosis dehiscence (5), postoperative bleeding in the
      mediastinum (1), fistula between trachea and transposition (1), paresis of the
      left recurrent nerve (8), infectious complications in the abdominal cavity (2),
      thoracic cavity (1), and early complications (2). The sixty-day mortality was 8%
      and this was mostly due to pulmonary complications (4 patients) but included
      coronary thrombosis (1) and transposition necrosis (1). CONCLUSION: The
      dominating complications of esophagectomy were pulmonary (20 %). The remaining
      serious complications cannot be completely eliminated but if diagnosed in time
      and treated in a correct algorithm they do not have to imminently threaten the
      lives of patients.

PMID- 22660224
TI  - Cured malakoplakia of the renal allograft followed by long-term good function: a
      case report.
AB  - BACKGROUND: Malakoplakia is an unusual chronic inflammatory disease with
      distinctive histopathological features rarely involving the parenchyma of a
      transplanted kidney, and to date less than ten cases have been reported. METHODS
      AND RESULTS: We present a case of malakoplakia of a kidney graft in a 31 year old
      woman after simultaneous kidney and pancreas transplantation, which was
      successfully treated with quinolones. After the treatment of malakoplakia, she
      was monitored regularly, and her renal and pancreas grafts functioned well for
      the following 9 years, which is 12 years post transplantation. Moreover, 1 year
      after treatment of malakoplakia she became pregnant and gave birth to a healthy
      child. CONCLUSION: Evaluation of a kidney biopsy sample represents the key to
      diagnosis of malakoplakia which is important for correct patient management.
      Treatment with antibiotics with intracellular penetration (quinolone type) may
      result in curing the disease. According to our knowledge, this is the first case
      of allograft renal malakoplakia after combined kidney and pancreas
      transplantation.

PMID- 22660223
TI  - A complex oncosurgical approach to increasing the resectability of colorectal
      cancer metastases - a case report.
AB  - AIM: In this case report, the authors aim to demonstrate the success of recent
      methods in the radical treatment of a patient with primary inoperable liver and
      subsequent colorectal cancer pulmonary metastases. METHODS: A 75 year old patient
      with inoperable bulky metastasis in the right hepatic lobe and insufficient
      future remnant liver volume was indicated for a stage procedure in the liver
      parenchyma. Embolization of the right branch of the portal vein was first
      performed with subsequent administration of stem cells into the contralateral
      liver lobe. Following compensatory growth of the left liver lobe, right-sided
      hepatectomy was performed with subsequent adjuvant oncological treatment. Six
      months after the surgery, a metastasis developed in the right pulmonary lobe
      which was solved by metastasectomy. RESULTS: The patient, one year after the
      diagnosis of inoperable liver metastasis, is completely healthy and free of signs
      of disease recurrence. CONCLUSION: A comprehensive oncosurgical approach using up
      to-date diagnostic and treatment options may offer patients with metastatic
      colorectal cancer, radical treatment with the hope of long-term quality survival.

PMID- 22660225
TI  - Vancomycin removal during low-flux and high-flux extended daily hemodialysis in
      critically ill septic patients.
AB  - AIMS: To determine the extent of vancomycin removal and vancomycin
      pharmacokinetics in septic patients with AKI using daily hemodialysis with
      polysulphone high-flux and low-flux membrane. METHODS: Five patients received 6 h
      daily dialysis with low-flux polysulphone membrane, four patients with high-flux
      polysulphone membrane. Vancomycin was administered over the last hour of
      dialysis. The maintenance dose was adjusted based on pre-hemodialysis serum
      concentrations. Patients were followed up for two days. RESULTS: Median
      percentage of vancomycin removal by low-flux membrane dialysis was 17% (8-38%)
      and by high-flux membrane dialysis was 31% (13-43%). Vancomycin clearance was
      only moderately higher in high-flux membrane dialysis (median 3.01 L/h, range
      2.34-3.5 L/h) compared to low-flux dialysis (median 2.48 L/h, range 0.53-5.68
      L/h) in the first day of the study. About two-fold higher vancomycin clearance in
      high-flux dialysis (median 3.62 L/h, range 1.37-5.07 L/h) was observed on the
      second day of the study than low-flux dialysis (median 1.74 L/h, range 0.75-30.94
      L/h). CONCLUSIONS: Both high-flux and low-flux membrane dialysis remove
      considerable amounts of vancomycin in critically ill septic patients with AKI.
      Application of vancomycin after each dialysis was required to maintain
      therapeutic concentrations.

PMID- 22660226
TI  - Usefulness of exercise tissue doppler echocardiography for prognostic
      stratification of congestive heart failure patients with left ventricular
      systolic dysfunction.
AB  - AIM: Determination of the importance of exercise tissue Doppler echocardiography
      in prognostic stratification of congestive heart failure patients with systolic
      dysfunction. METHODS: 106 patients with congestive heart failure and LVEF <= 45%
      on optimal pharmacotherapy were included in the study. Results of resting and
      post-exercise echocardiography, cardiopulmonary exercise test and serum BNP
      levels were available for all patients. Two patient groups were constituted,
      based on the prognostic classification. Group I contained 21 patients with poor
      prognosis (defined by predicted value of pVO2 < 76% together with both VE/VCO2
      slope > 32.7 and BNP > 210 pg/mL) and group II with 85 patients who did not meet
      the criteria. RESULTS: The patient groups significantly differed in indexed
      volume of left atrium, mitral regurgitation severity, rest and post-exercise
      systolic velocity of mitral annulus and in rest and post-exercise E/Em.
      Multivariate analysis identified E/Em as the only independent predictor of
      prognosis. E/Em at rest (post-exercise) >= 16.6 (>= 18.7) defined poor prognosis
      with sensitivity of 71% (86%) and specificity of 71% (71%). CONCLUSION: Our study
      suggests usefulness of exercise tissue Doppler echocardiography for prognostic
      stratification of patients with congestive heart failure with possible
      superiority to resting parameters.

PMID- 22660227
TI  - Protobothrops mangshanensis bite: first clinical report of envenoming and its
      treatment.
AB  - AIM: This case report presents envenoming by the Chinese pit viper Protobothrops
      mangshanensis (formerly Zhaoermia) and its treatment. METHODS: A 38 year old
      snake breeder suffered two-fang bites to elbow by a Chinese pit viper
      Protobothrops mangshanensis resulting in local edema of the affected arm. No
      other signs of envenoming appeared. On the 5(th) day following the bite a
      hematoma developed on the other arm which had been mechanically injured 14 days
      before. Laboratory testing revealed severe coagulopathy with hypofibrinogenemia
      and immeasurably prolonged coagulation times. RESULTS: As substitution therapy
      with fibrinogen and fresh frozen plasma was unsuccessful and specific antivenom
      is not produced, antivenin against some other Asian pit vipers GREEN PIT VIPER
      ANTIVENIN, Thai Red Cross, Thailand was applied. Three doses of antivenom
      reversed the course of the hemocoagulation disorder. CONCLUSION: The case
      confirms the persistence of active venom components affecting coagulation,
      difficulty in ameliorating the hemocoagulatin disorder caused by snake venom
      through substitution therapy and the effectiveness of delayed treatment using
      antivenin. It points out the potential risk of a clinically asymptomatic progress
      of envenoming by snake venoms containing hemocoagulation acting components, if
      the hemocoagulation disorder is not investigated and suitably treated. Therapy
      using the GREEN PIT VIPER ANTIVENIN, Thai Red Cross, Thailand in this case of
      envenomation by a Protobothrops mangshanensis bite proved to be applicable and
      the antivenom could be characterised as a paraspecific active.

PMID- 22660228
TI  - Ultrasound evaluation of fetal gender at 12-14 weeks.
AB  - AIMS: The aim of this study was to assess the feasibility and accuracy of fetal
      gender assignment by transabdominal ultrasound at 12-14 weeks of gestation.
      METHODS: Fetal gender assessment was performed in 1222 singleton pregnancies. In
      all fetuses the crown-rump length (CRL) was measured and the genital area of the
      fetus was examined in the mid-sagittal plane. The result of ultrasound
      examination was compared to the phenotypic sex of the newborn after delivery.
      RESULTS: The feasibility as well as accuracy in determining gender increased with
      growing fetal CRL. At CRL < 50 mm (gestational age < 11+4) the feasibility was
      39.1% and accuracy 30.5% (40.9% in male gender vs 24.3% in female gender). At CRL
      50-54.9 mm (gestational age 11+4 to 12+0) the feasibility was 63.5% and accuracy
      75.0% (89.1% in male gender vs 66.7% in female gender). At CRL 55-59.9 mm
      (gestational age 12+0 to 12+2) the feasibility was 90.5% and accuracy 96.6%
      (99.1% in male gender vs 93.5% in female gender). At CRL >= 60 mm (gestational
      age >= 12+2) the feasibility was 97.4% and accuracy 100.0% (100.0% in male gender
      vs 100.0% in female gender). CONCLUSIONS: Fetal gender may reliably be determined
      when CRL >= 60 mm (gestational age >= 12+2). Male gender may already be reliably
      determined when CRL >= 55 mm (gestational age >= 12+0). If CRL < 50 mm
      (gestational age < 11+4) the gender cannot be reliably predicted.

PMID- 22660229
TI  - Peripheral tissue oxygenation during standard CPB and miniaturized CPB (direct
      oxymetric tissue perfusion monitoring study).
AB  - AIM: The aim of this study was to compare the impact of standard cardiopulmonary
      bypass (CPB) with mini CPB on peripheral tissue perfusion. METHODS: 24 patients
      with ischemic heart disease scheduled for CPB were randomised to two groups:
      Group A (12 patients, standard CPB) and Group B (12 patients, mini CPB). Oxygen
      tension was measured with an optical multiparametric sensor inserted into the
      patient's deltoid muscle. RESULTS: Lower priming in Group B (870 +/- 221 mL) vs.
      Group A (1502 +/- 48 mL) and significantly reduced hemodilution during mini CPB
      (Group B 25.3 +/- 1.1% vs. Group A 30.1 +/- 2.3%) were recorded. Higher and
      continuous blood flow during perfusion was analysed in Group A (4.58 +/- 0.34
      L.min(-1)) and lower than calculated blood flow was found in Group B (3.49 +/-
      0.51 L.min(-1) vs. 4.66 +/- 0.38 L.min(-1)). There was a direct correlation
      between mean arterial pressure (MAP) and ptO2 in Group A during CPB and a direct
      correlation between pump blood flow and MAP during CPB in Group B. Higher levels
      of ptO2 during CPB and surgery after CPB in comparison with initial levels were
      found in Group B. Decreased ptO2 levels after surgery were found in both groups.
      CONCLUSION: Mini CPB enables perfusion with a relatively low flow. The results of
      this study suggest that a flow decrease in mini CPB is well tolerated by the
      organism.

PMID- 22660230
TI  - A complex case of fatal calciphylaxis in a female patient with
      hyperparathyroidism secondary to end stage renal disease of graft and coexistence
      of haemolytic uremic syndrome.
AB  - BACKGROUND: Calciphylaxis is a potentially fatal complication of persistent
      secondary hyperparathyroidism; its cause is still not clear. Unfortunately there
      is no close relation in severity of clinical picture, serological and
      pathological alteration. For this reason the prognosis is difficult to establish.
      Administration of sodium thiosulphate may reduce the precipitation of calcium
      crystals and improve the general clinical conditions before surgical
      parathyroidectomy, which seems the only therapeutic approach able to reduce the
      mortality risk in these patients. METHODS AND RESULTS: A 60 year old female
      patient suffering from End Renal Stage Disease, on haemodialysis from 2001 due to
      the onset of haemolytic uremic syndrome, underwent a kidney transplant in April
      2008. After transplantation there was a recurrence of the haemolytic uremic
      syndrome, with temporary worsening of the graft. Six months later there was a
      definite loss of graft and return to dialysis treatment. On April 2010 a severe
      systemic calciphylaxis related to secondary hyperparathyroidism was diagnosed.
      The patient underwent parathyroidectomy but, because of the unimproved clinical
      picture, treatment with sodium thiosulphate was initiated. There was only
      improvement in cutaneous lesions. The worsening general clinical condition of the
      patient caused death due to general septic complications. CONCLUSIONS: The
      coexistence of haemolytic uremic syndrome and secondary hyperpathyroidism makes
      the prognosis poor and, in this case, therapy, which counteracts calcium crystals
      precipitation, has no effect. Preventive parathyroidectomy can be considered as
      the only possible treatment.

PMID- 22660231
TI  - Endoscopic vs open saphenous vein harvest for coronary artery bypass grafting: a
      leg-related morbidity and histological comparison.
AB  - AIMS: The aim of this study was to compare coronary artery bypass grafting (CABG)
      using either endoscopic (EVH) or open harvest (OVH). Leg-related morbidity and
      histological comparison of the veins were the outcome measures. METHODS: One
      hundred consecutive patients scheduled for isolated CABG were randomly divided
      into two goups: an EVH and OVH group. Perioperative data were recorded. Patients
      were examined 7 days and 1 month postoperatively for leg-related morbidity.
      Samples for histological examination were taken from each harvested vein during
      the surgery. RESULTS: Postoperative pain was statistically significantly lower in
      the EVH group 7 days postoperatively but the incidence of haematoma was non
      statistically higher in the EVH group while swelling was higher in the OVH group.
      Almost 40% of all histological samples were described as showing endothelial
      damage. There was significantly more endothelial damage in the EVH than the OVH
      group. CONCLUSIONS: We confirmed the advantage of EVH in terms of leg-related
      morbidity as well as cosmetic effect. This method however, was associated with
      more acute endothelial damage of the graft. These results support concerns that
      endoscopic vein harvest may be connected with detrimental effects on vein
      endothelium which could promote a thrombogenic environment leading to a decrease
      in graft patency. This could be extremely important. The results suggest that
      further investigation of the long-term patency of vein grafts harvested
      endoscopically is required.

PMID- 22660232
TI  - Genetic variation in key molecules of the Th-17 immune response is not associated
      with risk for prosthetic joint infection in a Czech population.
AB  - BACKGROUND AND AIMS: Prosthetic Joint Infection (PJI) is a serious complication
      of Total Joint Arthroplasty (TJA). The Th-17 immune response characterised by IL
      (interleukin)-17A, IL-17F, IL-23, chemotactic cytokines and their receptors,
      plays a prominent role in the immune response to invading bacteria. In addition,
      high expression of IL-17A has been reported in PJI. The aim of this study was to
      investigate whether genetic variation in the key molecules of the Th-17 immune
      response can affect the risk for PJI. METHODS: Altogether ten Single Nucleotide
      Polymorphisms (SNPs) of IL17A (rs2275913), IL17F (rs763780), IL4 (rs2243250),
      IL12A (rs583911), IL12B (rs3212227 and (rs17860508), IL23R (rs7517847), CXCL1
      (rs4074), CXCL5 (rs425535) and CXCR2 (rs2230054) genes were genotyped by PCR with
      sequence specific primers (SSP) in 98 patients with PJI and two control groups 1)
      an aseptic TJA control (253 patients with TJA that did not develop PJI at least 6
      yrs. after the surgery) and 2) a population control (185 healthy control subjects
      without TJA). RESULTS: Allele, genotype and phenotype frequencies of investigated
      SNPs did not differ between the patients with PJI and control patients with
      aseptic TJA (p>0.05). There was no difference in the distribution of tested SNPs
      between patients with PJI and population controls without TJA (p>0.05) or between
      the two controls groups (p>0.05). CONCLUSIONS: We cannot nominate any of studied
      polymorphisms in IL17A, IL17F, IL4, IL12A, IL12B, IL23R, CXCL1, CXCL5 and CXCR2
      genes as risk factors for PJI in the Czech TJA patients examined.

PMID- 22660233
TI  - Osteoprotegerin gene polymorphism is not associated with prosthetic joint
      infection after total joint arthroplasty in the Czech population.
AB  - BACKGROUND AND AIMS: Osteoprotegerin (OPG; official gene symbol: TNFRSF11B) is
      considered a negative regulator of bone resorption via inhibition of osteoclast
      differentiation. Further, OPG expression has been detected in Prosthetic Joint
      Infection (PJI) a serious complication limiting the overall outcome of total
      joint arthroplasty (TJA). As OPG may be a candidate molecule for PJI
      pathogenesis, we investigated whether genetic variation in the OPG promoter,
      namely the SNP at position -163 was associated with PJI. METHODS: OPG -163 T/C
      SNP (rs3102735) was genotyped by polymerase chain reaction with sequence specific
      primers (PCR-SSP) in 98 Czech patients with PJI and two Czech control groups: 1)
      aseptic TJA control [251 patients with TJA who did not develop PJI at least 6
      yrs. after the surgery] and 2) population control (185 healthy control subjects
      without TJA). RESULTS: The distribution of OPG -163 SNP genotypes complied with
      the Hardy-Weinberg equilibrium in all three groups. The allele frequencies of OPG
      -163 SNP were similar in patients with PJI (minor allele frequency: 0.14), those
      with aseptic TJA (0.13) and population controls (0.14, P>0.05). Further, there
      was no significant difference in genotype or phenotype frequency (carriage rate)
      between patients with PJI and both control groups (P>0.05). CONCLUSIONS: In a
      Czech population, the OPG -163 T/C SNP has not been found to be associated with
      PJI.

PMID- 22660257
TI  - [Antidepressant drugs : a reasonable therapy for pruritus?].
AB  - Pruritus represents one of the most bothersome symptoms of skin and internal
      diseases, and can also occur without an underlying detectable cause. It is well
      known that chronic pruritus seriously affects the quality of life in patients.
      The management of pruritus is challenging, especially if the underlying cause is
      not identifiable. Besides therapy with increased dosage of non-sedating H1
      antihistamines, which is often not successful in severe pruritus, tri- or
      tetracyclic antidepressants and selective serotonin-reuptake inhibitors are
      recommended for therapy, as discussed in this review.

PMID- 22660258
TI  - [Tap water iontophoresis].
AB  - Since 1968, tap water iontophoresis has been employed as the method of choice for
      treating palmoplantar hyperhidrosis. Special electrodes also allow treatment of
      axillary hyperhidrosis. Tap water iontophoresis also can extend symptom -free
      intervals in dyshidrotic palmar eczema. The mechanism action is most likely a
      functional disturbance of the secretory mechanism of eccrine acini. During the
      induction phase, treatments are carried out once daily. Current direction may be
      switched before each treatment or, even better, kept constant until one side,
      preferably the dominant hand on the anode, is sweating normally. Then polarity is
      switched until both hands are adequately treated. During the weekly maintenance
      therapy, current direction is switched before each treatment. The most
      comfortable means of iontophoretic treatment employs pulsed direct current of
      high frequency (5-10 kHz) which is better tolerated than continuous direct
      current and also suitable for children. Side effects are minimal and transient.
      Only slight skin irritation or sensations of discomfort may occur during
      treatment. Electric burns and shocks can be avoided by following routine
      precautions. Contraindications for tap water iontophoresis are metallic implants,
      such as cardiac pacemakers, or orthopaedic joint or bone implants, if they are
      within the electric circuit. Defects in the skin barrier, which can not be
      protected by petrolatum or insulating tape, also represent a temporary
      contraindication. Treatment in pregnancy is contraindicated, since experience is
      lacking.

PMID- 22660272
TI  - Recurrent atrial septal defect device mobile thrombus in a patient with heart
      failure presenting with embolic stroke and decompensation.

PMID- 22660271
TI  - ER stress inhibits neuronal death by promoting autophagy.
AB  - Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative
      diseases but its relationship and role in disease progression remain unclear.
      Using genetic and pharmacological approaches, we showed that mild ER stress
      ("preconditioning") is neuroprotective in Drosophila and mouse models of
      Parkinson disease. In addition, we found that the combination of mild ER stress
      and apoptotic signals triggers an autophagic response both in vivo and in vitro.
      We showed that when autophagy is impaired, ER-mediated protection is lost. We
      further demonstrated that autophagy inhibits caspase activation and apoptosis.
      Based on our findings, we conclude that autophagy is required for the
      neuroprotection mediated by mild ER stress, and therefore ER preconditioning has
      potential therapeutic value for the treatment of neurodegenerative diseases.

PMID- 22660273
TI  - Quantifying trace gas uptake to tropospheric aerosol: recent advances and
      remaining challenges.
AB  - The interactions of trace gases with tropospheric aerosol can have significant
      effects on both gas phase and aerosol composition. In turn, this may affect the
      atmospheric oxidizing capacity, aerosol hygroscopicity and optical properties,
      and the lifetimes of trace aerosol species. Through the detailed description of
      specific reaction systems, this review article illustrates how detailed
      experimental studies of gas-particle interactions lead to both a comprehensive
      understanding of the underlying physical chemistry as well as accurate
      parameterizations for atmospheric modeling. The reaction systems studied
      illustrate the complexity in the field: (i) N(2)O(5) uptake, presented as a
      benchmark multiphase system, can lead to both NO(x) loss and halogen activation,
      (ii) loss of HO(2) on aqueous particles is surprisingly poorly studied given its
      potential importance for HO(x) loss, (iii) uptake of HNO(3) by marine aerosol and
      heterogeneous oxidation of organic-bearing particles are examples of how gas
      particle interactions can lead to substantial alteration of aerosol composition,
      and (iv) the uptake of glyoxal to ammonium sulfate aerosol leads to highly
      complex particle-phase chemistry. In addition, for the first time, this article
      presents the challenges that must be addressed in the design and interpretation
      of atmospheric gas-to-particle uptake experiments.

PMID- 22660274
TI  - Cyclophosphamide promotes engraftment of gene-modified cells in a mouse model of
      Fanconi anemia without causing cytogenetic abnormalities.
AB  - A major hurdle for hematopoietic stem cell (HSC) gene therapy for inherited bone
      marrow disorders, including Fanconi anemia (FA), is adequate engraftment of gene
      modified cells. A phenotypic defect in DNA repair renders FA patients sensitive
      to alkylating agents such as cyclophosphamide (Cy); however, at lower doses, Cy
      is well tolerated in the FA transplant setting. We tested whether non-alkylating
      agents could replace Cy for pretransplant conditioning to enhance engraftment of
      FANCA gene-modified hematopoietic cells. We compared Cy preconditioning with
      fludarabine (Flu) or cytarabine (AraC) or no conditioning as a control in fanca (
      -/- ) mutant mice receiving gene-modified bone marrow cells. Only mice
      conditioned with Cy exhibited appreciable engraftment of gene-modified cells by
      PCR and resistance to mitomycin C (MMC). Cy administration following
      transplantation increased gene marking levels in all animals treated, but highest
      gene marking and corresponding MMC resistance were observed in mice receiving Cy
      pre- and posttransplantation. Importantly, no cytogenetic abnormalities were
      observed in Cy-treated mice. We conclude that Cy is an effective and superior
      preparative regimen with respect to engraftment of lentivirus-transduced cells
      and functional correction in fanca ( -/- ) mice. Thus, appropriately dosed Cy may
      provide a suitable conditioning regimen for FA patients undergoing HSC gene
      therapy.

PMID- 22660275
TI  - Significance of IL-6 in the transition of hormone-resistant prostate cancer and
      the induction of myeloid-derived suppressor cells.
AB  - Hormone-resistant (HR) prostate cancers are highly aggressive and respond poorly
      to treatment. A better understanding of the molecular mechanisms involved in HR
      should lead to more rational approaches to therapy. The role of IL-6/STAT3
      signaling in the transition of HR with aggressive tumor behavior and its possible
      link with myeloid-derived suppressor cells (MDSCs) were identified. In the
      present study, murine prostate cancer cell line (TRAMP-C1) and a hormone
      resistant cell sub-line (TRAMP-HR) were used. Changes in tumor growth, invasion
      ability, and the responsible pathway were investigated in vitro and in vivo. We
      also examined the role of IL-6 in HR tumor progression and the recruitment of
      MDSCs. As seen in both in vitro and in vivo experiments, HR had aggressive tumor
      growth compared to TRAMP-C1. From mRNA and protein analysis, a higher expression
      of IL-6 associated with a more activated STAT3 was noted in HR tumor. When IL-6
      signaling in prostate cancer was blocked, aggressive tumor behavior could be
      overcome. The underlying changes included decreased cell proliferation, less
      epithelial-mesenchymal transition, and decreased STAT3 activation. In addition to
      tumor progression, circulating IL-6 levels were significantly correlated with
      MDSC recruitment in vivo. Inhibition of IL-6 abrogated the recruitment of MDSCs
      in tumor- bearing mice, associated with slower tumor growth and attenuated
      angiogenesis. In conclusion, altered IL-6/STAT3 signaling is crucial in HR
      transition, aggressive behavior, and MDSC recruitment. These findings provide
      evidence for therapeutically targeting IL-6 signaling in prostate cancer.

PMID- 22660277
TI  - You say tomato.

PMID- 22660278
TI  - A war not yet won.

PMID- 22660279
TI  - Split decision.

PMID- 22660280
TI  - Let's mine asteroids--for science and profit.

PMID- 22660276
TI  - The role of epigenetic regulation in stem cell and cancer biology.
AB  - Normal development and homeostasis requires a carefully coordinated gene
      expression program. Appropriate transcriptional regulation is maintained, in
      part, through epigenetic modifications of both DNA and histones. It is now
      apparent that the epigenetic landscape is complex and carefully controlled to
      both silence and activate gene transcription and that these states remain
      exquisitely poised for reversal. The deregulation of epigenetics in cancer is
      common and results in both the activation of oncogenes and the silencing of tumor
      suppressors. A tremendous amount of research corroborates the existence in many
      tumor types of a cancer stem cell that is both the origin and cell type
      responsible for resistance of tumors to current therapies. As our understanding
      of cancer stem cell biology continues, it is apparent that these cells are also
      under the influence of epigenetic regulation. We will discuss the cancer stem
      cell hypothesis and the role of epigenetics in both normal and cancer stem cell
      biology.

PMID- 22660292
TI  - Winners all round in telescope bid.

PMID- 22660293
TI  - Fracking boom spurs environmental audit.

PMID- 22660294
TI  - US beef tests cook up a storm.

PMID- 22660295
TI  - Reform falters after Europe's E. coli scare.

PMID- 22660296
TI  - Anarchists attack science.

PMID- 22660297
TI  - Polio's last stand.

PMID- 22660298
TI  - Scientists: your number is up.

PMID- 22660300
TI  - Endangered species: Sex and the single rhinoceros.

PMID- 22660301
TI  - Microglia: The constant gardeners.

PMID- 22660302
TI  - Resources: Stop squandering helium.

PMID- 22660308
TI  - Politics: Food safety body is bound to draw fire.

PMID- 22660303
TI  - HIV prevention: Bring safe sex to China.

PMID- 22660309
TI  - Biologics: Personalized drugs should cut care costs.

PMID- 22660310
TI  - Epidemiology: Reduce uncertainty in UK badger culling.

PMID- 22660311
TI  - Authorship: Include all institutes in publishing index.

PMID- 22660312
TI  - Nanotechnology: The importance of being modular.

PMID- 22660314
TI  - Evolutionary anthropology: Homo 'incendius'.

PMID- 22660313
TI  - Regenerative medicine: Reprogramming the injured heart.

PMID- 22660315
TI  - Condensed-matter physics: Repulsive polarons found.

PMID- 22660316
TI  - Immunology: Actin' dangerously.

PMID- 22660317
TI  - Cancer metabolism: Tumour friend or foe.

PMID- 22660319
TI  - The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche.
AB  - Adult stem cells support tissue homeostasis and repair throughout the life of an
      individual. During ageing, numerous intrinsic and extrinsic changes occur that
      result in altered stem-cell behaviour and reduced tissue maintenance and
      regeneration. In the Drosophila testis, ageing results in a marked decrease in
      the self-renewal factor Unpaired (Upd), leading to a concomitant loss of germline
      stem cells. Here we demonstrate that IGF-II messenger RNA binding protein (Imp)
      counteracts endogenous small interfering RNAs to stabilize upd (also known as os)
      RNA. However, similar to upd, Imp expression decreases in the hub cells of older
      males, which is due to the targeting of Imp by the heterochronic microRNA let-7.
      In the absence of Imp, upd mRNA therefore becomes unprotected and susceptible to
      degradation. Understanding the mechanistic basis for ageing-related changes in
      stem-cell behaviour will lead to the development of strategies to treat age-onset
      diseases and facilitate stem-cell-based therapies in older individuals.

PMID- 22660318
TI  - Heart repair by reprogramming non-myocytes with cardiac transcription factors.
AB  - The adult mammalian heart possesses little regenerative potential following
      injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac
      regeneration and contributes to loss of contractile function, pathological
      remodelling and susceptibility to arrhythmias. Cardiac fibroblasts account for a
      majority of cells in the heart and represent a potential cellular source for
      restoration of cardiac function following injury through phenotypic reprogramming
      to a myocardial cell fate. Here we show that four transcription factors, GATA4,
      HAND2, MEF2C and TBX5, can cooperatively reprogram adult mouse tail-tip and
      cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced
      expression of these factors in dividing non-cardiomyocytes in mice reprograms
      these cells into functional cardiac-like myocytes, improves cardiac function and
      reduces adverse ventricular remodelling following myocardial infarction. Our
      results suggest a strategy for cardiac repair through reprogramming fibroblasts
      resident in the heart with cardiogenic transcription factors or other molecules.

PMID- 22660320
TI  - A spectrograph for exoplanet observations calibrated at the centimetre-per-second
      level.
AB  - The best spectrographs are limited in stability by their calibration light
      source. Laser frequency combs are the ideal calibrators for astronomical
      spectrographs. They emit a spectrum of lines that are equally spaced in frequency
      and that are as accurate and stable as the atomic clock relative to which the
      comb is stabilized. Absolute calibration provides the radial velocity of an
      astronomical object relative to the observer (on Earth). For the detection of
      Earth-mass exoplanets in Earth-like orbits around solar-type stars, or of cosmic
      acceleration, the observable is a tiny velocity change of less than 10 cm s(-1),
      where the repeatability of the calibration--the variation in stability across
      observations--is important. Hitherto, only laboratory systems or spectrograph
      calibrations of limited performance have been demonstrated. Here we report the
      calibration of an astronomical spectrograph with a short-term Doppler shift
      repeatability of 2.5 cm s(-1), and use it to monitor the star HD 75289 and
      recompute the orbit of its planet. This repeatability should make it possible to
      detect Earth-like planets in the habitable zone of star or even to measure the
      cosmic acceleration directly.

PMID- 22660321
TI  - Metastability and coherence of repulsive polarons in a strongly interacting Fermi
      mixture.
AB  - Ultracold Fermi gases with tunable interactions provide a test bed for exploring
      the many-body physics of strongly interacting quantum systems. Over the past
      decade, experiments have investigated many intriguing phenomena, and precise
      measurements of ground-state properties have provided benchmarks for the
      development of theoretical descriptions. Metastable states in Fermi gases with
      strong repulsive interactions represent an exciting area of development. The
      realization of such systems is challenging, because a strong repulsive
      interaction in an atomic quantum gas implies the existence of a weakly bound
      molecular state, which makes the system intrinsically unstable against decay.
      Here we use radio-frequency spectroscopy to measure the complete excitation
      spectrum of fermionic (40)K impurities resonantly interacting with a Fermi sea of
      (6)Li atoms. In particular, we show that a well-defined quasiparticle exists for
      strongly repulsive interactions. We measure the energy and the lifetime of this
      'repulsive polaron', and probe its coherence properties by measuring the
      quasiparticle residue. The results are well described by a theoretical approach
      that takes into account the finite effective range of the interaction in our
      system. We find that when the effective range is of the order of the
      interparticle spacing, there is a substantial increase in the lifetime of the
      quasiparticles. The existence of such a long-lived, metastable many-body state
      offers intriguing prospects for the creation of exotic quantum phases in
      ultracold, repulsively interacting Fermi gases.

PMID- 22660322
TI  - Attractive and repulsive Fermi polarons in two dimensions.
AB  - The dynamics of a single impurity in an environment is a fundamental problem in
      many-body physics. In the solid state, a well known case is an impurity coupled
      to a bosonic bath (such as lattice vibrations); the impurity and its accompanying
      lattice distortion form a new entity, a polaron. This quasiparticle plays an
      important role in the spectral function of high-transition-temperature
      superconductors, as well as in colossal magnetoresistance in manganites. For
      impurities in a fermionic bath, studies have considered heavy or immobile
      impurities which exhibit Anderson's orthogonality catastrophe and the Kondo
      effect. More recently, mobile impurities have moved into the focus of research,
      and they have been found to form new quasiparticles known as Fermi polarons. The
      Fermi polaron problem constitutes the extreme, but conceptually simple, limit of
      two important quantum many-body problems: the crossover between a molecular Bose
      Einstein condensate and a superfluid with BCS (Bardeen-Cooper-Schrieffer) pairing
      with spin-imbalance for attractive interactions, and Stoner's itinerant
      ferromagnetism for repulsive interactions. It has been proposed that such quantum
      phases (and other elusive exotic states) might become realizable in Fermi gases
      confined to two dimensions. Their stability and observability are intimately
      related to the theoretically debated properties of the Fermi polaron in a two
      dimensional Fermi gas. Here we create and investigate Fermi polarons in a two
      dimensional, spin-imbalanced Fermi gas, measuring their spectral function using
      momentum-resolved photoemission spectroscopy. For attractive interactions, we
      find evidence for a disputed pairing transition between polarons and tightly
      bound dimers, which provides insight into the elementary pairing mechanism of
      imbalanced, strongly coupled two-dimensional Fermi gases. Additionally, for
      repulsive interactions, we study novel quasiparticles--repulsive polarons--the
      lifetime of which determines the possibility of stabilizing repulsively
      interacting Fermi systems.

PMID- 22660323
TI  - Complex shapes self-assembled from single-stranded DNA tiles.
AB  - Programmed self-assembly of strands of nucleic acid has proved highly effective
      for creating a wide range of structures with desired shapes. A particularly
      successful implementation is DNA origami, in which a long scaffold strand is
      folded by hundreds of short auxiliary strands into a complex shape. Modular
      strategies are in principle simpler and more versatile and have been used to
      assemble DNA or RNA tiles into periodic and algorithmic two-dimensional lattices,
      extended ribbons and tubes, three-dimensional crystals, polyhedra and simple
      finite two-dimensional shapes. But creating finite yet complex shapes from a
      large number of uniquely addressable tiles remains challenging. Here we solve
      this problem with the simplest tile form, a 'single-stranded tile' (SST) that
      consists of a 42-base strand of DNA composed entirely of concatenated sticky ends
      and that binds to four local neighbours during self-assembly. Although ribbons
      and tubes with controlled circumferences have been created using the SST
      approach, we extend it to assemble complex two-dimensional shapes and tubes from
      hundreds (in some cases more than one thousand) distinct tiles. Our main design
      feature is a self-assembled rectangle that serves as a molecular canvas, with
      each of its constituent SST strands--folded into a 3 nm-by-7 nm tile and attached
      to four neighbouring tiles--acting as a pixel. A desired shape, drawn on the
      canvas, is then produced by one-pot annealing of all those strands that
      correspond to pixels covered by the target shape; the remaining strands are
      excluded. We implement the strategy with a master strand collection that
      corresponds to a 310-pixel canvas, and then use appropriate strand subsets to
      construct 107 distinct and complex two-dimensional shapes, thereby establishing
      SST assembly as a simple, modular and robust framework for constructing
      nanostructures with prescribed shapes from short synthetic DNA strands.

PMID- 22660324
TI  - Hafnium isotope evidence for a transition in the dynamics of continental growth
      3.2 Gyr ago.
AB  - Earth's lithosphere probably experienced an evolution towards the modern plate
      tectonic regime, owing to secular changes in mantle temperature. Radiogenic
      isotope variations are interpreted as evidence for the declining rates of
      continental crustal growth over time, with some estimates suggesting that over
      70% of the present continental crustal reservoir was extracted by the end of the
      Archaean eon. Patterns of crustal growth and reworking in rocks younger than
      three billion years (Gyr) are thought to reflect the assembly and break-up of
      supercontinents by Wilson cycle processes and mark an important change in
      lithosphere dynamics. In southern West Greenland numerous studies have, however,
      argued for subduction settings and crust growth by arc accretion back to 3.8 Gyr
      ago, suggesting that modern-day tectonic regimes operated during the formation of
      the earliest crustal rock record. Here we report in situ uranium-lead, hafnium
      and oxygen isotope data from zircons of basement rocks in southern West Greenland
      across the critical time period during which modern-like tectonic regimes could
      have initiated. Our data show pronounced differences in the hafnium isotope-time
      patterns across this interval, requiring changes in the characteristics of the
      magmatic protolith. The observations suggest that 3.9-3.5-Gyr-old rocks
      differentiated from a >3.9-Gyr-old source reservoir with a chondritic to slightly
      depleted hafnium isotope composition. In contrast, rocks formed after 3.2 Gyr ago
      register the first additions of juvenile depleted material (that is, new mantle
      derived crust) since 3.9 Gyr ago, and are characterized by striking shifts in
      hafnium isotope ratios similar to those shown by Phanerozoic subduction-related
      orogens. These data suggest a transitional period 3.5-3.2 Gyr ago from an ancient
      (3.9-3.5 Gyr old) crustal evolutionary regime unlike that of modern plate
      tectonics to a geodynamic setting after 3.2 Gyr ago that involved juvenile crust
      generation by plate tectonic processes.

PMID- 22660325
TI  - Accelerated speciation in colour-polymorphic birds.
AB  - Colour polymorphism exemplifies extreme morphological diversity within
      populations. It is taxonomically widespread but generally rare. Theory suggests
      that where colour polymorphism does occur, processes generating and maintaining
      it can promote speciation but the generality of this claim is unclear. Here we
      confirm, using species-level molecular phylogenies for five families of non
      passerine birds, that colour polymorphism is associated with accelerated
      speciation rates in the three groups in which polymorphism is most prevalent. In
      all five groups, colour polymorphism is lost at a significantly greater rate than
      it is gained. Thus, the general rarity and phylogenetic dispersion of colour
      polymorphism is accounted for by a combination of higher speciation rate and
      higher transition rate from polymorphism to monomorphism, consistent with
      theoretical models where speciation is driven by fixation of one or more morphs.
      This is corroborated by evidence from a species-level molecular phylogeny of
      passerines, incorporating 4,128 (66.5%) extant species, that polymorphic species
      tend to be younger than monomorphic species. Our results provide empirical
      support for the general proposition, dating from classical evolutionary theory,
      that colour polymorphism can increase speciation rates.

PMID- 22660327
TI  - Genetic recombination is directed away from functional genomic elements in mice.
AB  - Genetic recombination occurs during meiosis, the key developmental programme of
      gametogenesis. Recombination in mammals has been recently linked to the activity
      of a histone H3 methyltransferase, PR domain containing 9 (PRDM9), the product of
      the only known speciation-associated gene in mammals. PRDM9 is thought to
      determine the preferred recombination sites--recombination hotspots--through
      sequence-specific binding of its highly polymorphic multi-Zn-finger domain.
      Nevertheless, Prdm9 knockout mice are proficient at initiating recombination.
      Here we map and analyse the genome-wide distribution of recombination initiation
      sites in Prdm9 knockout mice and in two mouse strains with different Prdm9
      alleles and their F(1) hybrid. We show that PRDM9 determines the positions of
      practically all hotspots in the mouse genome, with the exception of the pseudo
      autosomal region (PAR)--the only area of the genome that undergoes recombination
      in 100% of cells. Surprisingly, hotspots are still observed in Prdm9 knockout
      mice, and as in wild type, these hotspots are found at H3 lysine 4 (H3K4)
      trimethylation marks. However, in the absence of PRDM9, most recombination is
      initiated at promoters and at other sites of PRDM9-independent H3K4
      trimethylation. Such sites are rarely targeted in wild-type mice, indicating an
      unexpected role of the PRDM9 protein in sequestering the recombination machinery
      away from gene-promoter regions and other functional genomic elements.

PMID- 22660328
TI  - Recurrent network activity drives striatal synaptogenesis.
AB  - Neural activity during development critically shapes postnatal wiring of the
      mammalian brain. This is best illustrated by the sensory systems, in which the
      patterned feed-forward excitation provided by sensory organs and experience
      drives the formation of mature topographic circuits capable of extracting
      specific features of sensory stimuli. In contrast, little is known about the role
      of early activity in the development of the basal ganglia, a phylogenetically
      ancient group of nuclei fundamentally important for complex motor action and
      reward-based learning. These nuclei lack direct sensory input and are only
      loosely topographically organized, forming interlocking feed-forward and feed
      back inhibitory circuits without laminar structure. Here we use transgenic mice
      and viral gene transfer methods to modulate neurotransmitter release and neuronal
      activity in vivo in the developing striatum. We find that the balance of activity
      between the two inhibitory and antagonist pathways in the striatum regulates
      excitatory innervation of the basal ganglia during development. These effects
      indicate that the propagation of activity through a multi-stage network regulates
      the wiring of the basal ganglia, revealing an important role of positive feedback
      in driving network maturation.

PMID- 22660329
TI  - Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid
      beta.
AB  - Extracellular plaques of amyloid-beta and intraneuronal neurofibrillary tangles
      made from tau are the histopathological signatures of Alzheimer's disease.
      Plaques comprise amyloid-beta fibrils that assemble from monomeric and oligomeric
      intermediates, and are prognostic indicators of Alzheimer's disease. Despite the
      importance of plaques to Alzheimer's disease, oligomers are considered to be the
      principal toxic forms of amyloid-beta. Interestingly, many adverse responses to
      amyloid-beta, such as cytotoxicity, microtubule loss, impaired memory and
      learning, and neuritic degeneration, are greatly amplified by tau expression.
      Amino-terminally truncated, pyroglutamylated (pE) forms of amyloid-beta are
      strongly associated with Alzheimer's disease, are more toxic than amyloid-beta,
      residues 1-42 (Abeta(1-42)) and Abeta(1-40), and have been proposed as initiators
      of Alzheimer's disease pathogenesis. Here we report a mechanism by which pE-Abeta
      may trigger Alzheimer's disease. Abeta(3(pE)-42) co-oligomerizes with excess
      Abeta(1-42) to form metastable low-n oligomers (LNOs) that are structurally
      distinct and far more cytotoxic to cultured neurons than comparable LNOs made
      from Abeta(1-42) alone. Tau is required for cytotoxicity, and LNOs comprising 5%
      Abeta(3(pE)-42) plus 95% Abeta(1-42) (5% pE-Abeta) seed new cytotoxic LNOs
      through multiple serial dilutions into Abeta(1-42) monomers in the absence of
      additional Abeta(3(pE)-42). LNOs isolated from human Alzheimer's disease brain
      contained Abeta(3(pE)-42), and enhanced Abeta(3(pE)-42) formation in mice
      triggered neuron loss and gliosis at 3 months, but not in a tau-null background.
      We conclude that Abeta(3(pE)-42) confers tau-dependent neuronal death and causes
      template-induced misfolding of Abeta(1-42) into structurally distinct LNOs that
      propagate by a prion-like mechanism. Our results raise the possibility that
      Abeta(3(pE)-42) acts similarly at a primary step in Alzheimer's disease
      pathogenesis.

PMID- 22660330
TI  - Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia
      development.
AB  - How environmental cues regulate adult stem cell and cancer cell activity through
      surface receptors is poorly understood. Angiopoietin-like proteins (ANGPTLs), a
      family of seven secreted glycoproteins, are known to support the activity of
      haematopoietic stem cells (HSCs) in vitro and in vivo. ANGPTLs also have
      important roles in lipid metabolism, angiogenesis and inflammation, but were
      considered 'orphan ligands' because no receptors were identified. Here we show
      that the immune-inhibitory receptor human leukocyte immunoglobulin-like receptor
      B2 (LILRB2) and its mouse orthologue paired immunoglobulin-like receptor (PIRB)
      are receptors for several ANGPTLs. LILRB2 and PIRB are expressed on human and
      mouse HSCs, respectively, and the binding of ANGPTLs to these receptors supported
      ex vivo expansion of HSCs. In mouse transplantation acute myeloid leukaemia
      models, a deficiency in intracellular signalling of PIRB resulted in increased
      differentiation of leukaemia cells, revealing that PIRB supports leukaemia
      development. Our study indicates an unexpected functional significance of
      classical immune-inhibitory receptors in maintenance of stemness of normal adult
      stem cells and in support of cancer development.

PMID- 22660326
TI  - The tomato genome sequence provides insights into fleshy fruit evolution.
AB  - Tomato (Solanum lycopersicum) is a major crop plant and a model system for fruit
      development. Solanum is one of the largest angiosperm genera and includes annual
      and perennial plants from diverse habitats. Here we present a high-quality genome
      sequence of domesticated tomato, a draft sequence of its closest wild relative,
      Solanum pimpinellifolium, and compare them to each other and to the potato genome
      (Solanum tuberosum). The two tomato genomes show only 0.6% nucleotide divergence
      and signs of recent admixture, but show more than 8% divergence from potato, with
      nine large and several smaller inversions. In contrast to Arabidopsis, but
      similar to soybean, tomato and potato small RNAs map predominantly to gene-rich
      chromosomal regions, including gene promoters. The Solanum lineage has
      experienced two consecutive genome triplications: one that is ancient and shared
      with rosids, and a more recent one. These triplications set the stage for the
      neofunctionalization of genes controlling fruit characteristics, such as colour
      and fleshiness.

PMID- 22660332
TI  - Addendum: Verbal and non-verbal intelligence changes in the teenage brain.

PMID- 22660334
TI  - Professional resilience revisited.
AB  - Case managers' lives have always been stressful; with new and compounding
      regulations, fewer staff and personal stressors, individual health and
      professional work can suffer, unless something is done. This article discusses
      practical methods to improve resilience, thereby decreasing stress.

PMID- 22660331
TI  - AMPK regulates NADPH homeostasis to promote tumour cell survival during energy
      stress.
AB  - Overcoming metabolic stress is a critical step for solid tumour growth. However,
      the underlying mechanisms of cell death and survival under metabolic stress are
      not well understood. A key signalling pathway involved in metabolic adaptation is
      the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. Energy
      stress conditions that decrease intracellular ATP levels below a certain level
      promote AMPK activation by LKB1. Previous studies showed that LKB1-deficient or
      AMPK-deficient cells are resistant to oncogenic transformation and tumorigenesis,
      possibly because of the function of AMPK in metabolic adaptation. However, the
      mechanisms by which AMPK promotes metabolic adaptation in tumour cells are not
      fully understood. Here we show that AMPK activation, during energy stress,
      prolongs cell survival by redox regulation. Under these conditions, NADPH
      generation by the pentose phosphate pathway is impaired, but AMPK induces
      alternative routes to maintain NADPH and inhibit cell death. The inhibition of
      the acetyl-CoA carboxylases ACC1 and ACC2 by AMPK maintains NADPH levels by
      decreasing NADPH consumption in fatty-acid synthesis and increasing NADPH
      generation by means of fatty-acid oxidation. Knockdown of either ACC1 or ACC2
      compensates for AMPK activation and facilitates anchorage-independent growth and
      solid tumour formation in vivo, whereas the activation of ACC1 or ACC2 attenuates
      these processes. Thus AMPK, in addition to its function in ATP homeostasis, has a
      key function in NADPH maintenance, which is critical for cancer cell survival
      under energy stress conditions, such as glucose limitations, anchorage
      independent growth and solid tumour formation in vivo.

PMID- 22660335
TI  - Fight or flight? Resolving conflict in the professional workplace.

PMID- 22660336
TI  - Heart failure rehospitalization of the Medicare FFS patient: a state-level
      analysis exploring 30-day readmission factors.
AB  - PURPOSE OF STUDY: Heart failure readmission among the elderly is frequent and
      costly to both the patient and the Medicare trust fund. In this study, the
      authors explore the factors that are associated with states having heart failure
      readmission rates that are higher than the U.S. national rate. PRIMARY PRACTICE
      SETTING(S): Acute inpatient hospital settings. METHODOLOGY AND SAMPLE: 50 state
      level data and multivariate regression analysis is used. The dependent variable
      Heart Failure 30-day Readmission Worse than U.S. Rate is based on adult Medicare
      Fee-for-Service patients hospitalized with a primary discharge diagnosis of heart
      failure and for which a subsequent inpatient readmission occurred within 30 days
      of their last discharge. RESULTS: One key variable found--states with a higher
      resident population speaking a primary language other than English at home--that
      is significantly associated with a decrease in probability in states ranking
      "worse" on heart failure 30-day readmission. Whereas, states with a higher median
      income, more total days of care per 1,000 Medicare enrollees, and a greater
      percentage of Medicare enrollees with prescription drug coverage have a greater
      probability for heart failure 30-day readmission to be "worse" than the U.S.
      national rate. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Case management
      interventions targeting health literacy may be more effective than other factors
      to improve state-level hospital status on heart failure 30-day readmission.
      Factors such as total days of care per 1,000 Medicare enrollees and improving
      patient access to postdischarge medication(s) may not be as important as
      literacy. Interventions aimed to prevent disparities should consider higher
      income population groups as vulnerable for readmission.

PMID- 22660338
TI  - Motivational interviewing: building rapport with clients to encourage desirable
      behavioral and lifestyle changes.
AB  - PURPOSE/OBJECTIVE: As professional case managers seek to improve outcomes,
      including the health status of their clients, it becomes imperative to gather and
      assess as much relevant information as possible to identify and address the
      client's needs in a holistic manner. Motivational interviewing is a highly
      effective technique case managers employ for this purpose. They also rely on it
      to move their clients toward a course of successful, desirable, and sustainable
      change, such as healthier diet, exercise, self-care, and adherence to medications
      regime and follow-up care. PRIMARY PRACTICE SETTING: Across the case management
      spectrum, including hospitals, accountable care organizations, patient-centered
      medical homes, physician practices, clinics, and other settings in which case
      managers work with clients and their support systems. FINDINGS/CONCLUSIONS:
      Motivational interviewing is a highly effective technique for gathering accurate
      and comprehensive information that is supportive of and additive to the
      assessment phase of the case management process. Using motivational interviewing,
      case managers can more readily uncover health and lifestyle needs of their
      clients. This results in building trusting relationships and developing rapport
      with clients, which can motivate them to move toward successful and desirable
      change. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: The design and implementation
      of a comprehensive and effective case management plan of care is facilitated by
      motivational interviewing, whereby professional case managers establish
      collaborative, respectful, trusting and individualized relationships with
      clients. Using the specific principles and techniques of motivational
      interviewing, case managers take a holistic approach to care to address a
      client's willingness and ability to change; addressing self-confidence and other
      emotional triggers that affect change and support the client's ability to embrace
      and sustain positive change.

PMID- 22660340
TI  - Nursing perception of patient transitions from hospitals to home with home
      health.
AB  - PURPOSE OF THE STUDY: The study's purpose was to determine nurses' opinions of
      sending patients from the hospital to home with home health services. PRIMARY
      PRACTICE SETTING: The study occurred in the Charleston, South Carolina, Tricounty
      area (Berkeley, Charleston, and Dorchester counties). Home health agencies and
      hospitals were invited to participate. METHODOLOGY AND SAMPLE: The study used a
      survey design to gather information on nursing perceptions of current practices
      and needed changes to improve transition of patients. The population was nurses
      (licensed practical nurses (LPNs) and registered nurses (RNs)) employed at
      inpatient hospitals or home health agencies in the area. Thirty-four RNs
      responded with no LPNs respondents. Agency administrators/chief nursing officers
      agreed for their agencies to participate and distributed the survey using a
      Research Electronic Data Capture (REDCap) Internet-based survey tool. Using the
      survey results and information from a literature review, the study developed a
      list of propositions, which participating administrators reviewed, for improving
      transitions to home. RESULTS: Both home health and hospital nurses reported a
      need to improve the process of sending patients from hospital to home with home
      health services. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: This study provides
      hospitals and home health agencies with propositions to facilitate the
      establishment of a process to communicate effectively patients care needs and
      streamline the discharging patients from the hospital to home health care; thus,
      improving patient transition. Case managers and discharge planners will need
      interagency collaboration along with evidence-based interventions to transition
      patients from the hospital to home with home health services with various
      populations. Direct patient care nurses in both hospital and home health settings
      should share the same accountability as case managers to ensure successful
      transitions.

PMID- 22660341
TI  - Beyond the care episode:  patient-centered case management along the continuum.

PMID- 22660342
TI  - Reflections of a worker's compensation case manager.

PMID- 22660343
TI  - Legal & regulatory issues.

PMID- 22660344
TI  - Getting unstuck! A new way of thinking, part 3.

PMID- 22660345
TI  - Returning the TBI patient to work; challenges in the worker's compensation
      system.

PMID- 22660366
TI  - Quantitative analysis of gait coordination based on gait events in children with
      cerebral palsy.
AB  - OBJECTIVE: The objective of this study was to quantify gait coordination of the
      lower limbs in children with cerebral palsy (CP) based on gait events. DESIGN:
      The kinematic data of 50 children with typical development and 26 children with
      CP prerehabilitation and postrehabilitation were recorded. The hip and knee joint
      angles in the sagittal plane on both sides were obtained at six gait events. Then
      a gait coordination index (GCI) model was established based on the gait features
      extracted from the joint angles of the children with typical development using
      kernel-based principal component analysis, which was then used to calculate the
      GCI of children with CP. One-way analysis of variance was used to compare GCI and
      joint angles at each gait event. Intraclass correlation coefficient was
      calculated to evaluate the reliability of GCI in two trials separated by a day.
      RESULTS: GCI in children with CP postrehabilitation was significantly higher than
      that in the children with typical development (P < 0.05) but significantly lower
      than that in children with CP prerehabilitation (P < 0.05). There are significant
      differences in GCI for children with CP prerehabilitation between level I, level
      II, and level III (P < 0.05). The results of intraclass correlation coefficients
      (>0.8) indicated that the obtained GCIs were reliable. CONCLUSIONS: GCI can
      reflect gait coordination of lower limbs in children with CP and may be a useful
      tool for rehabilitation assessment.

PMID- 22660367
TI  - The usefulness of bladder reconditioning before indwelling urethral catheter
      removal from stroke patients.
AB  - OBJECTIVE: The aim of this study was to determine the effects of bladder
      reconditioning by indwelling urethral catheter (IUC) clamping before IUC removal
      in stroke patients. DESIGN: Sixty patients with stroke were randomized to 0-, 1-,
      and 3-day IUC clamping groups. IUCs were removed without clamping in the 0-day
      group. In the other two groups, IUCs were clamped for 4 hrs followed by 5 mins of
      urinary drainage, a cycle repeated over 24 hrs in the 1-day and over 72 hrs in
      the 3-day clamping groups. Time to first voiding (FV), first voided volume (FV
      vol), residual urine volume after FV, mean void volume, and residual urine volume
      on the third day after IUC removal were measured. We also recorded the voiding
      method such as self-voiding or intermittent catheterization, incidence of urinary
      tract infection, subjective complaints, and other complications. RESULTS: Time to
      FV, FV-vol, residual urine volume after FV, voiding method, mean voided volume,
      and residual urine volume on the third day after IUC removal had no significant
      difference among three groups, nor between the 0-day and the other two clamping
      groups. We observed a strong negative correlation between age and FV-vol. Of the
      patients in the 1- and 3-day clamping groups, 3 (7.5%) had symptomatic urinary
      tract infection and 9 (22.5%) complained of urinary leakage during IUC clamping
      program. CONCLUSIONS: Bladder reconditioning through IUC clamping has no
      noticeable benefits in stroke patients and may induce additional problems. These
      findings suggest that IUC removal without clamping is superior to IUC clamping
      for bladder reconditioning in stroke patients.

PMID- 22660368
TI  - Perceived exercise self-efficacy as a predictor of exercise behavior in
      individuals aging with spinal cord injury.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesized association
      between exercise self-efficacy and exercise behavior, controlling for demographic
      variables and clinical characteristics, in a sample of individuals with spinal
      cord injuries. DESIGN: A cross-sectional national survey of 612 community
      dwelling adults with spinal cord injury in the United States ranging from 18 to
      89 yrs of age was conducted. Sample consisted of 63.1% men with a mean (SD)
      duration of 15.8 (12.79) yrs postinjury; 86.3% reported using a wheelchair.
      RESULTS: Self-efficacy was the only independent variable that consistently
      predicted all four exercise outcomes. Self-efficacy beliefs were significantly
      related to frequency and intensity of resistance training (R(2) change = 0.08 and
      0.03, respectively; P < 0.01 for all) and aerobic training (R(2) change = 0.07
      and 0.05, respectively; P < 0.01 for all), thus explaining between 3% and 8% of
      the variance. Hierarchical linear regression analysis revealed that controlling
      for other demographic and physical capability variables, the age-related
      variables made statistically significant contributions and explained between 1%
      and 3% of the variance in aerobic exercise frequency and intensity (R(2) change =
      0.01 and 0.03, respectively; P < 0.01 for all). Clinical functional
      characteristics but not demographic variables explained participation in
      resistance exercise. CONCLUSIONS: Self-efficacy beliefs play an important role as
      predictors of exercise. Variations in exercise intensity along the age continuum
      have implications for exercise prescription and composition. Future research
      should replicate findings with objective activity measures.

PMID- 22660369
TI  - Do botulinum toxins have a role in the management of neuropathic pain?: a focused
      review.
AB  - Botulinum neurotoxin (BoNT) is usually used in physiatric practice in the
      treatment of spasticity and dystonia. Research involving both animal and human
      subjects has emerged suggesting potential benefits in painful neuropathic
      conditions. The animal data strongly support the use of BoNT in the treatment of
      sensitized pain states. BoNT is probably effective at treating postherpetic
      neuralgia, probably or possibly effective at treating postoperative/posttraumatic
      neuropathic pain, and probably effective at treating painful diabetic neuropathy.
      BoNT's proposed mechanism of action is described as decreasing sensitized
      nociception in four ways by (1) inhibiting glutamate release in peripheral
      tissues, (2) decreasing calcitonin gene-related peptide release in peripheral
      tissue, (3) decreasing transient receptor potential cation channel subfamily V
      member 1 trafficking to peripheral neuron cell membrane, and (4) decreasing
      substance P release in peripheral tissue. This review discusses pertinent
      cellular/animal basic science research in conjunction with clinical research with
      regard to the role of BoNT in treating neuropathic pain.

PMID- 22660370
TI  - Virtual electric power wheelchair driving performance of individuals with spastic
      cerebral palsy.
AB  - OBJECTIVE: Upper limb spasticity may impair the use of control interfaces such as
      joysticks for many individuals with disabilities such as cerebral palsy (CP). The
      aims of this study were to compare the driving performance of those with CP to
      that of control participants, to identify the impact of lead time on performance,
      and to compare two joystick designs, a standard movement sensing joystick and a
      novel isometric joystick. DESIGN: This study used a repeated-measures design to
      compare the performance of a group of participants with CP to that of
      participants without disabilities in a two-dimensional simulated driving task on
      a computer screen using the two control interfaces. The driving trials used
      varying "lead times," or the amount of warning time available to make movement
      decisions and turns. A total of 34 participants with CP and without disability
      were matched by age and sex into two groups. RESULTS: Participants with CP had
      lower driving performance in most variables of interest compared with controls.
      However, surprisingly, reducing lead time also reduced some performance errors,
      possibly because of more deliberate driving. The isometric joystick outperformed
      the movement sensing joystick in terms of performance errors but contributed to a
      prolonged reaction time. CONCLUSIONS: The isometric joystick was preferred by
      participants over the movement sensing joystick in this study and may be a future
      alternative for individuals with CP for both power mobility and computer access
      tasks.

PMID- 22660371
TI  - Constraint-induced movement therapy alters cerebral blood flow in subacute post
      stroke patients.
AB  - We attempted to evaluate patterns of hemispheric activation, according to
      cerebral blood flow changes, in post-stroke patients during motor tasks with and
      without arm restriction. Bilateral continuous middle cerebral artery monitoring
      of 6 healthy subjects (control group) and 28 post-stroke patients by transcranial
      Doppler sonography was executed while performing three simple motor tasks using
      the paretic or nondominant (in controls) hand: ball grasping, pegs insertion, and
      "eating" with a spoon. The nonaffected or dominant (in controls) arm was free and
      thereafter restricted. Mean blood flow velocity and flow velocity changes during
      the tests were estimated. No significant mean blood flow velocity changes were
      found in the healthy subjects. Significant elevation of mean blood flow velocity
      in damaged middle cerebral artery was recorded in post-stroke patients after
      restricting the undamaged hand. This may explain the positive effect of
      constraint-induced movement therapy on upper limb function.

PMID- 22660372
TI  - Posttraumatic confusion predicts patient cooperation during traumatic brain
      injury rehabilitation.
AB  - Scant research has examined the relationship between posttraumatic confusion
      (PTC) and cooperation during rehabilitation from moderate to severe traumatic
      brain injury. In this study, PTC and cooperation were examined in a prospective
      cohort of 74 inpatients with traumatic Brain Injury. Confusion was measured using
      the Confusion Assessment Protocol. Cooperation was rated on a 0-100 scale by
      rehabilitation therapists. Using multiple regression analysis, PTC significantly
      predicted cooperation (R(2) = 0.33, P < 0.001). Age at injury, education, days
      since injury, and Glasgow Come Scale scores were not significant predictors.
      Bivariate analyses indicated that four PTC symptoms significantly predicted
      poorer cooperation: daytime hypersomnolence (rho = -0.42, P < 0.001), agitation
      (rho = -0.39, P = 0.001), psychosis (rho = -0.39, P = 0.001), and cognitive
      impairment (rho = -0.24, P = 0.04). Results provide empirical support that PTC is
      associated with poorer cooperation and empirical justification for interventions
      to manage confusion during early recovery from traumatic brain injury.

PMID- 22660373
TI  - Symphalangism: ankylosis of the interphalangeal joints.

PMID- 22660374
TI  - Cephalad sensory loss as clinical manifestation of charcot spine in spinal cord
      injury.

PMID- 22660375
TI  - A randomized single-blind controlled trial comparing two monochromatic near
      infrared light devices: implications for tissue heating and safety.
AB  - OBJECTIVE: Use of near-infrared light (NIR) is becoming more commonplace in the
      treatment of different pathologies; however, its safety in terms of heat
      generation and penetration has not been documented. The purpose of this
      investigation was to determine and compare skin surface and underlying tissue
      temperature response during and for 15 mins after a 30-min NIR application to the
      posterior lower leg using two different NIR devices (Anodyne and HealthLight) and
      one sham treatment. With this information, recommendations regarding potential
      adverse skin reactions, including burns, can be made. In addition, these results
      can serve as a reference for further studies. DESIGN: This single-blind
      randomized controlled study used a repeated-measures design. Fifteen healthy
      college-age individuals randomly received 30-min treatments with two different
      near-infrared devices and one sham device to their lower leg. A thermistor
      underneath the diode and a thermocouple with temperature sensors at three depths
      measured the temperature at skin surface and in deep tissues, respectively, every
      minute during the treatment and for 15 mins posttreatment. RESULTS: After 30 mins
      of treatment, there was a significant temperature increase between the NIR
      devices underneath the diodes and all tissue depths and the control. The skin
      temperature underneath the treatment diodes increased about 9.5 degrees C from
      baseline to 40 degrees C. There was no difference between the tissue temperature
      changes in response to the irradiation with the two NIR heating devices. A
      limitation of the study is that the entire sample was drawn from a healthy
      college population. CONCLUSIONS: The surface and underlying tissue temperature
      heating produced by the two NIR devices is within limits considered safe for
      healthy subjects.

PMID- 22660376
TI  - Modeling spatial tuning of adaptation of the angular vestibulo-ocular reflex.
AB  - Gain adaptation of the yaw angular vestibular ocular reflex (aVOR) induced in
      side-down positions has gravity-independent (global) and -dependent (localized)
      components. When the head oscillation angles are small during adaptation,
      localized gain changes are maximal in the approximate position of adaptation.
      Concurrently, polarization vectors of canal-otolith vestibular neurons adapt
      their orientations during these small-angle adaptation paradigms. Whether there
      is orientation adaptation with large amplitude head oscillations, when the head
      is not localized to a specific position, is unknown. Yaw aVOR gains were
      decreased by oscillating monkeys about a yaw axis in a side-down position in a
      subject-stationary visual surround for 2 h. Amplitudes of head oscillation ranged
      from 15 degrees  to 180 degrees . The yaw aVOR gain was tested in darkness at 0.5
      Hz, with small angles of oscillation (+/-15 degrees ) while upright and in tilted
      positions. The peak value of the gain change was highly tuned for small angular
      oscillations during adaptation and significantly broadened with larger
      oscillation angles during adaptation. When the orientation of the polarization
      vectors associated with the gravity-dependent component of the neural network
      model was adapted toward the direction of gravity, it predicted the localized
      learning for small angles and the broadening when the orientation adaptation was
      diminished. The model-based analysis suggests that the otolith orientation
      adaptation plays an important role in the localized behavior of aVOR as a
      function of gravity and in regulating the relationship between global and
      localized adaptation.

PMID- 22660377
TI  - Postural reorientation does not cause the locomotor after-effect following rotary
      locomotion.
AB  - After a period of stepping on a rotating platform, blindfolded subjects
      demonstrate a tendency to unconsciously turn when stepping in place, an after
      effect known as podokinetic after-rotation (PKAR). Recent studies have also
      reported a change in postural orientation following the adaptive period and have
      suggested that this is causally related to PKAR. Here, we assess changes in trunk
      orientation following platform adaptation and determine their relationship to
      PKAR. Specifically, we determine whether a reorganized standing posture causes
      PKAR. Ten subjects stepped on a platform rotating at 60 degrees /s for 10 min,
      with a cadence of 100 steps/min. Following adaptation, a significant PKAR
      response was seen, with a mean yaw rotation velocity of 6.0 +/- 2.2 degrees /s.
      In addition to this dynamic after-effect, there was a significant twist of the
      trunk with respect to the feet when standing still (6.9 degrees  +/- 4.5 degrees
      ; mean +/- SD), confirming the presence of a postural reorientation after-effect.
      However, the magnitudes of the two after-effects did not correlate (r = 0.06, p =
      0.87). Furthermore, in a second experiment, a prolonged passive twist of the
      trunk was used to induce postural reorientation. However, in this case, PKAR was
      not induced. These results demonstrate that PKAR is not an automatic consequence
      of reorganized standing posture.

PMID- 22660387
TI  - Prebiotic chemistry in eutectic solutions at the water-ice matrix.
AB  - A crystalline ice matrix at subzero temperatures can maintain a liquid phase
      where organic solutes and salts concentrate to form eutectic solutions. This
      concentration effect converts the confined reactant solutions in the ice matrix,
      sometimes making condensation and polymerisation reactions occur more favourably.
      These reactions occur at significantly high rates from a prebiotic chemistry
      standpoint, and the labile products can be protected from degradation. The
      experimental study of the synthesis of nitrogen heterocycles at the ice-water
      system showed the efficiency of this scenario and could explain the origin of
      nucleobases in the inner Solar System bodies, including meteorites and extra
      terrestrial ices, and on the early Earth. The same conditions can also favour the
      condensation of monomers to form ribonucleic acid and peptides. Together with the
      synthesis of these monomers, the ice world (i.e., the chemical evolution in the
      range between the freezing point of water and the limit of stability of liquid
      brines, 273 to 210 K) is an under-explored experimental model in prebiotic
      chemistry.

PMID- 22660396
TI  - Specific alterations of the microRNA transcriptome and global network structure
      in colorectal cancer after treatment with MAPK/ERK inhibitors.
AB  - The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase
      (ERK) pathway has a master control role in various cancer-related biological
      processes as cell growth, proliferation, differentiation, migration, and
      apoptosis. It also regulates many transcription factors that control microRNAs
      (miRNAs) and their biosynthetic machinery. To investigate on the still poorly
      characterised global involvement of miRNAs within the pathway, we profiled the
      expression of 745 miRNAs in three colorectal cancer (CRC) cell lines after
      blocking the pathway with three different inhibitors. This allowed the
      identification of two classes of post-treatment differentially expressed (DE)
      miRNAs: (1) common DE miRNAs in all CRC lines after treatment with a specific
      inhibitor (class A); (2) DE miRNAs in a single CRC line after treatment with all
      three inhibitors (class B). By determining the molecular targets, biological
      roles, network position of chosen miRNAs from class A (miR-372, miR-663b, miR
      1226*) and class B (miR-92a-1*, miR-135b*, miR-720), we experimentally
      demonstrated that they are involved in cell proliferation, migration, apoptosis,
      and globally affect the regulation circuits centred on MAPK/ERK signaling.
      Interestingly, the levels of miR-92a-1*, miR-135b*, miR-372, miR-720 are
      significantly higher in biopsies from CRC patients than in normal controls; they
      also are significantly higher in CRC patients with mutated KRAS than in those
      with wild-type genotypes (Wilcoxon test, p < 0.05): the latter could be a
      downstream effect of ERK pathway overactivation, triggered by KRAS mutations.
      Finally, our functional data strongly suggest the following miRNA/target pairs:
      miR-92a-1*/PTEN-SOCS5; miR-135b*/LATS2; miR-372/TXNIP; miR-663b/CCND2.
      Altogether, these results contribute to deepen current knowledge on still
      uncharacterized features of MAPK/ERK pathway, pinpointing new oncomiRs in CRC and
      allowing their translation into clinical practice and CRC therapy.

PMID- 22660412
TI  - Theoretical studies of atmospheric reaction mechanisms in the troposphere.
AB  - The chemistry of the atmosphere encompasses a vast number of reactions acting on
      a plethora of intermediates. These reactions, occurring sequentially and in
      parallel, give rise to intertwined and irreducible mechanisms describing the
      complex chemical transformations of organic and inorganic compounds in the
      atmosphere. The complexity of this system is that it requires combined
      experimental, theoretical, and modeling approaches to elucidate the
      characteristics of the individual reactions, and their mutual interaction. In
      this review, we describe recent results from quantum chemical and theoretical
      kinetic studies of relevance to atmospheric chemistry. The review first
      summarizes the most commonly used theoretical methodologies. It then examines the
      VOC oxidation initiation channels by OH, O(3), NO(3) and Cl, followed by the
      reactions of the alkyl, alkoxy, alkylperoxy and Criegee intermediates active in
      the subsequent oxidation steps. Specific systems such as the oxidation of
      aromatics and the current state of knowledge on OH-regeneration in VOC oxidation
      are also discussed, as well as some inorganic reactions.

PMID- 22660413
TI  - Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.
AB  - The biogenesis of exosomes, small secreted vesicles involved in signalling
      processes, remains incompletely understood. Here, we report evidence that the
      syndecan heparan sulphate proteoglycans and their cytoplasmic adaptor syntenin
      control the formation of exosomes. Syntenin interacts directly with ALIX through
      LYPX(n)L motifs, similarly to retroviral proteins, and supports the intraluminal
      budding of endosomal membranes. Syntenin exosomes depend on the availability of
      heparan sulphate, syndecans, ALIX and ESCRTs, and impact on the trafficking and
      confinement of FGF signals. This study identifies a key role for syndecan
      syntenin-ALIX in membrane transport and signalling processes.

PMID- 22660414
TI  - Genome-wide RNAi screening identifies human proteins with a regulatory function
      in the early secretory pathway.
AB  - The secretory pathway in mammalian cells has evolved to facilitate the transfer
      of cargo molecules to internal and cell surface membranes. Use of automated
      microscopy-based genome-wide RNA interference screens in cultured human cells
      allowed us to identify 554 proteins influencing secretion. Cloning, fluorescent
      tagging and subcellular localization analysis of 179 of these proteins revealed
      that more than two-thirds localize to either the cytoplasm or membranes of the
      secretory and endocytic pathways. The depletion of 143 of them resulted in
      perturbations in the organization of the COPII and/or COPI vesicular coat
      complexes of the early secretory pathway, or the morphology of the Golgi complex.
      Network analyses revealed a so far unappreciated link between early secretory
      pathway function, small GTP-binding protein regulation, actin cytoskeleton
      organization and EGF-receptor-mediated signalling. This work provides an
      important resource for an integrative understanding of global cellular
      organization and regulation of the secretory pathway in mammalian cells.

PMID- 22660420
TI  - Particles, air quality, policy and health.
AB  - The diversity of ambient particle size and chemical composition considerably
      complicates pinpointing the specific causal associations between exposure to
      particles and adverse human health effects, the contribution of different sources
      to ambient particles at different locations, and the consequent formulation of
      policy action to most cost-effectively reduce harm caused by airborne particles.
      Nevertheless, the coupling of increasingly sophisticated measurements and models
      of particle composition and epidemiology continue to demonstrate associations
      between particle components and sources (and at lower concentrations) and a wide
      range of adverse health outcomes. This article reviews the current approaches to
      source apportionment of ambient particles and the latest evidence for their
      health effects, and describes the current metrics, policies and legislation for
      the protection of public health from ambient particles. A particular focus is
      placed on particles in the ultrafine fraction. The review concludes with an
      extended evaluation of emerging challenges and future requirements in methods,
      metrics and policy for understanding and abating adverse health outcomes from
      ambient particles.

PMID- 22660415
TI  - MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC
      components.
AB  - The genomic stability of all organisms depends on the precise partition of
      chromosomes to daughter cells. The spindle assembly checkpoint (SAC) senses
      unattached kinetochores and prevents premature entry to anaphase, thus ensuring
      that all chromosomes attach to opposite spindle poles (bi-orientation) during
      mitosis. MPS1 is an evolutionarily conserved protein kinase required for the SAC
      and chromosome bi-orientation. Yet, its primary cellular substrate has remained
      elusive. We show that fission yeast Mph1 (MPS1 homologue) phosphorylates the
      kinetochore protein Spc7 (KNL1/Blinkin homologue) at the MELT repeat sequences.
      This phosphorylation promotes the in vitro binding to the Bub1-Bub3 complex,
      which is required for kinetochore-based SAC activation (Mad1-Mad2-Mad3
      localization) and chromosome alignment. Accordingly, a non-phosphorylatable spc7
      12A mutation abolishes kinetochore targeting of Bub1-Bub3, whereas a phospho
      mimetic spc7-12E mutation forces them to localize at kinetochores throughout the
      entire cell cycle, even in the absence of Mph1. Thus, MPS1/Mph1 kinase locating
      at the unattached kinetochores initially creates a mark, which is crucial for SAC
      activation and chromosome bi-orientation. This mechanism seems to be conserved in
      human cells.

PMID- 22660421
TI  - Sirenomelia:  four further cases with discussion of associated upper limb
      defects.
AB  - Sirenomelia, also known as the 'mermaid malformation/syndrome', is a rare,
      serious congenital anomaly characterized by variable degrees of fusion of the
      lower limbs and associated severe malformations of the lower vertebral and
      genitourinary systems. In this report, we describe a series of African patients
      with sirenomelia. We present the clinical and radiological features of four black
      South African patients and illustrate some of the rarer associated abnormalities,
      which include asymmetrical upper limb defects, not confined to the radial ray.
      The clinical phenotypic overlap between caudal dysgenesis, VACTERL association
      and sirenomelia in our patients is highlighted, lending support to the theory
      that these entities may be different manifestations of a single pathogenic
      process.

PMID- 22660433
TI  - The pitfalls of body temperature measurements.

PMID- 22660438
TI  - KlenTaq polymerase replicates unnatural base pairs by inducing a Watson-Crick
      geometry.
AB  - Many candidate unnatural DNA base pairs have been developed, but some of the best
      replicated pairs adopt intercalated structures in free DNA that are difficult to
      reconcile with known mechanisms of polymerase recognition. Here we present
      crystal structures of KlenTaq DNA polymerase at different stages of replication
      for one such pair, dNaM-d5SICS, and show that efficient replication results from
      the polymerase itself, inducing the required natural-like structure.

PMID- 22660439
TI  - ATM and MET kinases are synthetic lethal with nongenotoxic activation of p53.
AB  - The p53 tumor suppressor orchestrates alternative stress responses including cell
      cycle arrest and apoptosis, but the mechanisms defining cell fate upon p53
      activation are poorly understood. Several small-molecule activators of p53 have
      been developed, including Nutlin-3, but their therapeutic potential is limited by
      the fact that they induce reversible cell cycle arrest in most cancer cell types.
      We report here the results of a genome-wide short hairpin RNA screen for genes
      that are lethal in combination with p53 activation by Nutlin-3, which showed that
      the ATM and MET kinases govern cell fate choice upon p53 activation. Genetic or
      pharmacological interference with ATM or MET activity converts the cellular
      response from cell cycle arrest into apoptosis in diverse cancer cell types
      without affecting expression of key p53 target genes. ATM and MET inhibitors also
      enable Nutlin-3 to kill tumor spheroids. These results identify new pathways
      controlling the cellular response to p53 activation and aid in the design of p53
      based therapies.

PMID- 22660440
TI  - Prediction of the tacrolimus population pharmacokinetic parameters according to
      CYP3A5 genotype and clinical factors using NONMEM in adult kidney transplant
      recipients.
AB  - PURPOSE: Tacrolimus is a commonly used immunosuppressant in solid organ
      transplantation recipients, but it is characterized by a narrow therapeutic range
      and large inter-individual variability. The purpose of this study was to
      establish a population pharmacokinetic (PK) model of tacrolimus and evaluate the
      influence of clinical covariates, including the genetic polymorphisms of the
      cytochrome P450 3A5 gene (CYP3A5) and gene encoding P-glycoprotein (ABCB1), on
      the PK parameters in adult Korean kidney transplant recipients. METHODS: Clinical
      data were collected retrospectively for 400 days after the initiation of a
      tacrolimus-based immunosuppression therapy. Data from 2,788 trough blood samples
      obtained from 80 subjects were used to perform a population PK analysis with a
      nonlinear mixed-effect model (NONMEM). RESULTS: The estimated population mean
      values of clearance (CL/F) and volume of distribution (V/F) were 22.9 L/h and 716
      L, respectively, and the k(a) was fixed to 4.5 h-1. The CYP3A5 genotype,
      hematocrit level, and post-operative days were identified as the main covariates
      that influence CL/F, and body weight was found to have a significant effect on
      V/F. Other covariates, including ABCB1 genotype, corticosteroid dosage, sex, and
      other clinical data, did not contribute to the pharmacokinetics of tacrolimus.
      CONCLUSIONS: This tacrolimus population PK model will be a valuable tool in
      developing rational guidelines and provides a basis for individualized therapy
      after kidney transplantation in clinical settings of Korea.

PMID- 22660441
TI  - Pharmacokinetic-pharmacodynamic model of fimasartan applied to predict the
      influence of a high fat diet on its blood pressure-lowering effect in healthy
      subjects.
AB  - PURPOSE: Fimasartan is a non-peptide angiotensin II receptor antagonist which
      selectively blocks the AT(1) receptor. The aim of our study was to perform a
      population pharmacokinetic-pharmacodynamic (PK-PD) analysis of fimasartan to
      evaluate the effect of food on the mechanistic PK-PD relationship. METHODS: This
      was a food-drug interaction single-center study involving 24 healthy subjects
      that was designed as a randomized, open-label, single-dosing, two-way crossover
      trial. Extensive PK data was obtained on blood samples collected at 0, 0.5, 1, 2,
      2.5, 3, 4, 6, 8, 12, and 24 h post-dosing and five systolic/diastolic blood
      pressure (BP) measurements made at 0, 4, 8, 12 and 24 h post-dosing and used to
      construct a mixed effect model (NONMEM, ver. 6.2). RESULTS: A two-compartment
      linear PK model with zero-order (fasted) or Weibull (fed with high-fat diet)
      absorption best described the PK of fimasartan. Relative bioavailability
      decreased by 37 % when the subjects were given a high-fat diet. CONCLUSIONS: The
      turnover PK-PD model combined with pre-defined cosine function for circadian
      rhythm described the BP changes measured within 24 h after dosing better than the
      effect compartment or transduction models. To predict the influence of a high-fat
      diet on the blood pressure-lowering effect of fimasartan in healthy subjects, we
      simulated changes in BP when fimasartan was given daily for 30 days. The
      overlapping pattern of simulated BP curves in the fasted versus fed group
      demonstrated that a high-fat diet would not cause a clinically significant
      reduction in the BP-lowering effect of fimasartan, despite a significant
      reduction in bioavailability.

PMID- 22660442
TI  - Tacrolimus pharmacokinetics in the early post-liver transplantation period and
      clinical applicability via Bayesian prediction.
AB  - PURPOSE: To define and validate a pharmacokinetic (PK) model for tacrolimus (TAC)
      that includes patient pathophysiology and has clinical applicability in the first
      2 weeks post-liver transplantation (PLT). METHODS: Routine monitoring records
      [dose, trough levels (C(min)), demographics, biochemistry] from 75 patients
      treated with TAC (Prograf(r)) PLT were used to develop a population PK model
      (employing NONMEM(r)) testing for predictors of oral clearance (CL/F) according
      to bedside evidence and primarily with aspartate aminotransferase (AST), albumin
      (ALB), and hematocrit (HCT). Patients were catergorized into subgroups with above
      and below "normal" thresholds for AST (500 U/L), ALB (2.5 g/dL), and HCT (28 %),
      respectively. The model was validated with ten patients from the same period and
      15 more recent patients. An empirical Bayes method was developed and applied to
      the prediction of individual profiles serving as a dose adjustment tool. RESULTS:
      The number of days PLT (Days PLT) was a key variable during the first 2 weeks,
      with a dichotomy in the mono-compartmental parameters for 0-3 Days PLT and 4-15
      Days PLT. During 0-3 Days PLT, AST levels, indicative of allograft functionality
      (and TAC metabolism), were crucial predictors of elimination. Three groups were
      identified with the following clearances: CL/F0-3 = 8.93 L/h for AST >= 500 U/L
      and CL/F0-3 = 11.0 L/h for AST <500 U/L. During 4-15 Day PLT, low values of ALB
      (<2.5 g/dL) and HCT (<28 %) combined were determinant of a patient subgroup with
      a tendency to underexposure and complexity in empirical dose adjustment. The
      CL/F4-15 = 25.1 L/h for this subgroup compared to CL/F4-15 = 17.1 L/h for the
      others in that period. The elimination half-life for individual patients varied
      over tenfold so that a large number of subjects were not at steady state, making
      the use of a PK model necessary to achieve rapidly and safely the target
      concentration for TAC in LT. Validation of the model demonstrated that both bias
      and precision were within acceptable limits. CONCLUSION: For TAC therapy,
      covariate models using mixed effects methods are most useful when combined with
      patient-specific biochemical assays as well as clinical evidence. In such cases,
      the observed C(min) and Bayes methods can provide the most likely individual PK
      parameters, hence the optimal next dose to reach individualized target levels for
      each patient.

PMID- 22660445
TI  - Luminescent hybrid materials of lanthanide beta-diketonate and mesoporous host
      through covalent and ionic bonding with anion metathesis.
AB  - Luminescent mesoporous materials were prepared by performing an anion metathesis
      reaction on ionic liquid modified SBA15, which has imidazolium chloride bridging
      units. The lanthanide beta-diketonate complex anion was successfully anchored
      onto the SBA15 framework after the anion metathesis reaction. The resulting
      materials were characterized by FTIR, TEM, TGA, small-angle X-ray powder
      diffraction (SAXRD) and nitrogen adsorption-desorption isotherms. The
      photoluminescent properties of these materials were investigated in detail, and
      the results reveal that these hybrid mesoporous SBA15, prepared through this
      preparation approach, present favorable photoluminescent behavior such as high
      luminescent quantum efficiencies and long luminescent lifetimes.

PMID- 22660444
TI  - Population pharmacokinetics of lamotrigine in Indian epileptic patients.
AB  - PURPOSE: The aim of this analysis was to describe the pharmacokinetics of oral
      lamotrigine (LTG) in Indian epileptic patients using a population pharmacokinetic
      (PPK) modeling approach to confirm that the PK is similar to that of the
      Caucasian population, and to evaluate and confirm the impact of covariates
      predictive of inter-individual variability using a simulation platform. METHODS:
      Blood samples were obtained from 95 patients, and LTG plasma concentrations were
      determined. Population PK modeling was performed using NONMEM. A one-compartment
      PK model with first-order absorption and elimination was used to describe the LTG
      PK. Log-likelihood profiling and normalized prediction distribution errors (NPDE)
      were used for model evaluation. A simulation study was performed to investigate
      dose regimens. RESULTS: Clearance (CL) was estimated to be 2.27 L/h with inter
      individual variability (IIV) of 29 CV%. Volume of distribution (V) was estimated
      to be 53.6 L (31 CV% IIV). Body weight and concurrent use of carbamazepine and
      valproate were identified as significant covariates on clearance. Log-likelihood
      profiling indicated that parameters could be estimated with adequate precision,
      and NPDE indicated that the model adequately described the data observed. The
      simulation study illustrated the impact of carbamazepine and valproate on LTG PK,
      and negligible differences in PK between Indian and Caucasian patients.
      CONCLUSIONS: This is the first PK analysis of LTG in Indian patients. The
      population PK model developed adequately described the data observed. Comparison
      of identified PK parameters with previous PK analyses in Caucasian patients
      indicates that CL of LTG is similar, while V is somewhat lower compared with
      Caucasian patients, but this is not expected to lead to relevant differences in
      PK profiles during steady state.

PMID- 22660443
TI  - Azole interactions with multidrug therapy in pediatric oncology.
AB  - Patients with cancer receive multidrug therapy. Antineoplastic agents and
      supportive care drugs are often administered together, leading to potential drug
      drug interactions. These interactions may have significant clinical implications
      in terms of toxicity or a decrease in the efficacy of the treatment administered.
      Here, we focus on the role of azoles and their main pharmacokinetic interactions
      with the principal classes of drugs used in pediatric oncology. The co
      administration of azoles and antineoplastic agents, corticosteroids,
      immunosuppressants, antacids, antiemetics, antiepileptic drugs and analgesics was
      investigated, and a practical guide on the management of these drugs when
      administered together is provided.

PMID- 22660456
TI  - Design and controlled emission properties of bioorganometallic compounds composed
      of uracils and organoplatinum(II) moieties.
AB  - The bioorganometallic platinum(II) compounds PtU6 and PtU5 were designed by the
      conjugation of the corresponding uracil derivative and the organoplatinum(II)
      compound [4-octyloxy-(C^N^N)PtCl]. The single crystal X-ray structure
      determination of PtU6 revealed the formation of the dimeric structure through
      intermolecular hydrogen bonds between the uracil moieties of two independent
      molecules, wherein each hydrogen-bonded dimer was connected through Pt(II)-Pt(II)
      and pi-pi interactions. The tuning of the emission properties of the
      organoplatinum(II) compounds was achieved by changing the direction of hydrogen
      bonding sites and the molecular scaffold having two 2,6-dihexamidopyridine
      moieties as a complementary hydrogen bonding site for the uracil moiety, which
      depends on the regulation of the aggregated structures, to induce the Pt(II)
      Pt(II) and pi-pi interactions.

PMID- 22660466
TI  - The impact of 24 h consultant shop floor presence on emergency department
      performance: a natural experiment.
AB  - OBJECTIVES: As a result of gaps in middle-grade cover in the emergency department
      it became necessary for consultants to work some night shifts. This study aimed
      to examine the effect of this change in practice on performance. METHODS: A
      prospective observational study was conducted. Staffing and workload variables
      were collected over a period of 6 months in a single district general emergency
      department. The outcomes assessed were process times, the proportion of patients
      admitted and the proportion of patients returning within 7 days. RESULTS:
      Consultants worked 26 of 182 night shifts during the period studied. There were
      no differences in the number of patients present in the department at the start
      of the middle-grade or consultant night shifts. Fewer patients presented per hour
      during middle-grade night shifts: 3.8 patients per hour versus 4.4 patients per
      hour during consultant nights. Compared with middle-grade night shifts, the
      median waiting time was on average 19.6 min less and the median emergency
      department length of stay was 20.5 min less during consultant night shifts. The
      proportion of patients admitted from the emergency department was on average 3.9%
      less than during middle-grade night shifts but there was no difference in the
      proportion returning within 7 days. CONCLUSION: In this small single-site study,
      a consultant working nights has been shown to reduce process times and the rate
      of admission. It remains unclear whether such improvements would be sustained in
      the longer term.

PMID- 22660467
TI  - Reduction of gastric inflation by use of a pressure relief valve connected to an
      acoustic expiration control device during mouth-to-mask ventilation of a manikin
      model of an unprotected airway.
AB  - BACKGROUND: Gastric inflation is a significant issue when ventilation of the
      unprotected airway is performed. The purpose of this study was to evaluate a
      prototype pressure relief valve with an acoustic expiration control mechanism
      connected to two different masks. METHODS: 12 non-physician healthcare
      professionals (group 1) and 10 newly certified dentists (group 2) performed 10
      cycles of cardiopulmonary resuscitation on a manikin using this device compared
      with mouth-to-mouth technique. Dentists also employed a mask without the valve.
      Lower oesophageal sphincter pressures had been adjusted to 1.5 kPa (group 1) and
      0.3 kPa (group 2); the valve relief pressure to 1.5 kPa (group 1) and 2.0 kPa
      (group 2). RESULTS: In group 1 tidal volumes by valve mask techniques (medians
      350 and 400 ml) differed minimally from mouth-to-mouth ventilation (medians 475
      and 600 ml). Almost no gastric inflation was observed. Gastric inflation only
      occurred using the safety valve connected to the mask (median 122 ml) and the
      mask alone (median 260 ml) (p=0.004). Only in group 1 the acoustic device
      delivered adequate signals. CONCLUSION: Gastric inflation occurred less
      frequently and to a lesser extent when the valve was connected, going ahead with
      a trend towards lower tidal volumes. The protective effect of the safety valve
      may be of benefit even if it leads to smaller tidal volumes.

PMID- 22660473
TI  - Managing physical therapy resources: an analogy to the freedom of the commons and
      the need for collective action.
AB  - Tragedy results when we each pursue our own best interest in a society that
      believes in the freedom of a commons, such as clean air, fresh water, or natural
      fishing grounds. The purpose of this editorial is to consider how resources
      related to healthcare, and specifically to the delivery of physical therapy, can
      suffer the tragedy of the commons, and to consider an alternative strategy by
      which we can manage physical therapy resources effectively through collective
      action.

PMID- 22660474
TI  - Favourability: concept, distinctive characteristics and potential usefulness.
AB  - The idea of analysing the general favourability for the occurrence of an event
      was presented in 2006 through a mathematical function. However, even when
      favourability has been used in species distribution modelling, the conceptual
      framework of this function is not yet well perceived among many researchers. The
      present paper is conceived for providing a wider and more in-depth presentation
      of the idea of favourability; concretely, we aimed to clarify both the concept
      and the main distinctive characteristics of the favourability function,
      especially in relation to probability and suitability, the most common outputs in
      species distribution modelling. As the capabilities of the favourability function
      go beyond species distribution modelling, we also illustrate its usefulness for
      different research disciplines for which this function remains unknown. In
      particular, we stressed that the favourability function has potential to be
      applied in all the cases where the probability of occurrence of an event is
      analysed, such as, for example, habitat selection or epidemiological studies.

PMID- 22660477
TI  - Structure and functional interaction of the extracellular domain of human GABA(B)
      receptor GBR2.
AB  - Inhibitory neurotransmission is mediated primarily by GABA. The metabotropic
      GABA(B) receptor is a G protein-coupled receptor central to mammalian brain
      function. Malfunction of GABA(B) receptor has been implicated in several
      neurological disorders. GABA(B) receptor functions as a heterodimeric assembly of
      GBR1 and GBR2 subunits, where GBR1 is responsible for ligand-binding and GBR2 is
      responsible for G protein coupling. Here we demonstrate that the GBR2 ectodomain
      directly interacts with the GBR1 ectodomain to increase agonist affinity by
      selectively stabilizing the agonist-bound conformation of GBR1. We present the
      crystal structure of the GBR2 ectodomain, which reveals a polar heterodimeric
      interface. We also identify specific heterodimer contacts from both subunits, and
      GBR1 residues involved in ligand recognition. Lastly, our structural and
      functional data indicate that the GBR2 ectodomain adopts a constitutively open
      conformation, suggesting a structural asymmetry in the active state of GABA(B)
      receptor that is unique to the GABAergic system.

PMID- 22660479
TI  - Rational regulation of learning dynamics by pupil-linked arousal systems.
AB  - The ability to make inferences about the current state of a dynamic process
      requires ongoing assessments of the stability and reliability of data generated
      by that process. We found that these assessments, as defined by a normative
      model, were reflected in nonluminance-mediated changes in pupil diameter of human
      subjects performing a predictive-inference task. Brief changes in pupil diameter
      reflected assessed instabilities in a process that generated noisy data. Baseline
      pupil diameter reflected the reliability with which recent data indicate the
      current state of the data-generating process and individual differences in
      expectations about the rate of instabilities. Together these pupil metrics
      predicted the influence of new data on subsequent inferences. Moreover, a task-
      and luminance-independent manipulation of pupil diameter predictably altered the
      influence of new data. Thus, pupil-linked arousal systems can help to regulate
      the influence of incoming data on existing beliefs in a dynamic environment.

PMID- 22660478
TI  - State and location dependence of action potential metabolic cost in cortical
      pyramidal neurons.
AB  - Action potential generation and conduction requires large quantities of energy to
      restore Na(+) and K(+) ion gradients. We investigated the subcellular location
      and voltage dependence of this metabolic cost in rat neocortical pyramidal
      neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy
      efficiency, we found that action potential initiation in the axon initial segment
      (AIS) and forward propagation into the axon were energetically inefficient,
      depending on the resting membrane potential. In contrast, action potential
      backpropagation into dendrites was efficient. Computer simulations predicted
      that, although the AIS and nodes of Ranvier had the highest metabolic cost per
      membrane area, action potential backpropagation into the dendrites and forward
      propagation into axon collaterals dominated energy consumption in cortical
      pyramidal neurons. Finally, we found that the high metabolic cost of action
      potential initiation and propagation down the axon is a trade-off between energy
      minimization and maximization of the conduction reliability of high-frequency
      action potentials.

PMID- 22660480
TI  - Electrocorticography links human temporoparietal junction to visual perception.
AB  - Electrical stimulation of visual cortex can produce a visual percept (phosphene).
      We electrically stimulated visual cortex in humans implanted with subdural
      electrodes while recording from other brain sites. Phosphene perception occurred
      only if stimulation evoked high-frequency gamma oscillations in the
      temporoparietal junction (TPJ), a brain region associated with visual extinction
      and neglect. Electrical stimulation of TPJ modified the detectability of low
      contrast visual stimuli.

PMID- 22660481
TI  - The novel two-dimensional strain reflects improvement and remodeling of left
      ventricular function better than conventional echocardiographic parameters after
      aortic valve repair in pediatric patients.
AB  - We aimed to evaluate the outcome and regional and global left-ventricular (LV)
      function after aortic valve repair in children with congenital aortic valve
      disease. Thirty-two consecutive patients with a mean age of 12.62 years (4 months
      to 18 years) undergoing aortic valve repair due to valve stenosis (AS group, n =
      21) or aortic regurgitation (AR group, n = 11) were studied during a follow-up
      period of 12 months regarding change and adaptation of myocardial function using
      conventional and novel echocardiographic methods, including two-dimensional (2D)
      strain echocardiogram. Conventional and 2D strain echocardiographic studies were
      performed and analyzed off-line using commercially available software (EchoPac
      6.1.0, GE). Peak aortic valve gradient decreased from 62.04 +/- 30.34 mmHg before
      surgery to 22.80 +/- 14.13 mmHg 2 weeks after surgery and to 35.73 +/- 22.11 mmHg
      12 months after surgery (p = 0.01). The degree of AR decreased significantly to
      grade 0 in 20 children and to grade I in 12. There was a significant decrease of
      thickness of the interventricular septum (IVS) and posterior wall resulting in
      improvement of LV mass index (p = 0.007, p = 0.043, and p = 0.001, respectively).
      Significant decrease of myocardial thickness was found, especially in the IVS, in
      the AS group (p = 0.008), and a significant decrease in LV end-diastolic
      dimension (EDD) was found in the AR group (p = 0.007). 2D strain analysis showed
      that global peak strain, global systolic strain rate, and global early diastolic
      strain rates improved significantly for all patients during the study period
      after aortic valve repair (p < 0.001, p = 0.037, and p = 0.018, respectively).
      The global strain and strain rates correlated significantly to IVS thickness (r =
      0.002 and r = 0.003, respectively), LV mass index (r = 0.02 and r = 0.015,
      respectively), and EDD (r = 0.26 and r = 0.005, respectively). Aortic valve
      repair surgery in pediatric patients results in improvement of global and
      regional systolic and diastolic LV parameters, which was better shown by 2D
      strain parameters rather than conventional echocardiographic parameters.

PMID- 22660482
TI  - Role of the transient outward potassium current in the genesis of early
      afterdepolarizations in cardiac cells.
AB  - AIMS: The transient outward potassium current (I(to)) plays important roles in
      action potential (AP) morphology and dynamics; however, its role in the genesis
      of early afterdepolarizations (EADs) is not well understood. We aimed to study
      the effects and mechanisms of I(to) on EAD genesis in cardiac cells using
      combined experimental and computational approaches. METHODS AND RESULTS: We first
      carried out patch-clamp experiments in isolated rabbit ventricular myocytes
      exposed to H(2)O(2) (0.2 or 1 mM), in which EADs were induced at a slow pacing
      rate. EADs were eliminated by either increasing the pacing rate or blocking I(to)
      with 2 mM 4-aminopyridine. In addition to enhancing the L-type calcium current
      (I(Ca,L)) and the late sodium current, H(2)O(2) also increased the conductance,
      slowed inactivation, and accelerated recovery from the inactivation of I(to).
      Computer simulations showed that I(to) promoted EADs under the condition of
      reduced repolarization reserve, consistent with the experimental observations.
      However, EADs were only promoted in the intermediate ranges of the I(to)
      conductance and the inactivation time constant. The underlying mechanism is that
      I(to) lowers the AP plateau voltage into the range at which the time-dependent
      potassium current (namely I(Ks)) activation is further slowed and I(Ca,L) is
      available for reactivation, leading to voltage oscillations to manifest EADs.
      Further experimental studies in cardiac cells of other species validated the
      theoretical predictions. CONCLUSION: In cardiac cells, I(to), with a proper
      conductance and inactivation speed, potentiates EADs by setting the AP plateau
      into the voltage range where I(Ca,L) reactivation is facilitated and I(Ks)
      activation is slowed.

PMID- 22660483
TI  - A cross-sectional survey on prevalence and risk factors for persistent
      postsurgical pain 1 year after total hip and knee replacement.
AB  - BACKGROUND AND OBJECTIVES: There is a paucity of large multi-institutional
      surveys to determine the prevalence of and risk factors for persistent pain after
      total hip (THR) and knee (TKR) replacements. We surveyed a variety of practices
      and patients and also correlated persistent pain with health-related quality-of
      life outcomes. METHODS: From October 10, 2007, to March 15, 2010, patients who
      had undergone primary THR or TKR with a minimum follow-up of 1 year were
      identified. A previously published questionnaire to identify persistent
      postsurgical pain that included a 36-item Short Form Health Survey was mailed to
      this group. Independent risk factors for persistent pain were identified with
      logistic regression. RESULTS: Responses from 1030 patients who underwent surgery
      at some point in time between June 13, 2006, and June 24, 2009, were analyzed
      (32% response rate). Forty-six percent of patients reported persistent pain (38%
      after THR and 53% after TKR) with a median average pain score of 3 of 10 and
      worst pain score of 5. Independent risk factors for persistent pain were female
      sex (odds ratio [OR], 1.23), younger age (OR, 0.97), prior surgery on hip or knee
      (OR, 1.39), knee versus hip replacement (OR, 1.65), lower-quality postsurgical
      pain control (OR, 0.9), and presence of pain in other areas of the body (OR,
      2.09). All scores in the 36-item Short Form Health Survey were worse (8%-28%
      decrease) in patients with persistent postsurgical pain (P < 0.001). CONCLUSIONS:
      Persistent postsurgical pain is common after THR and TKR and is associated with
      reduced health-related quality of life, although our survey may be biased by the
      low response rate and retrospective recall bias. Nonmodifiable risk factors may
      lead to risk stratification. Severity of acute postoperative pain may be a
      modifiable risk factor.

PMID- 22660484
TI  - A prospective, randomized comparison between perivascular and perineural
      ultrasound-guided axillary brachial plexus block.
AB  - BACKGROUND: This prospective, randomized, observer-blinded study compared
      perivascular (PV) and perineural (PN) ultrasound-guided axillary brachial plexus
      block (AXB) for upper extremity surgery. METHODS: Fifty patients were randomly
      allocated to receive a PV (n = 25) or PN (n = 25) ultrasound-guided AXB. The
      local anesthetic agent (lidocaine 1.5% with epinephrine 5 MUg/mL) and total
      volume (32 mL) were identical in all subjects. For both groups, the
      musculocutaneous nerve was first located and then anesthetized using 8 mL.
      Subsequently, in the PV group, 24 mL was deposited dorsal to the axillary artery
      (6-o'clock position). In contrast, for the PN group, the median, ulnar, and
      radial nerves were individually anesthetized with volumes of 8 mL. During the
      performance of the block, the performance time, number of needle passes, and
      complications (vascular puncture, paresthesia) were recorded. Subsequently, a
      blinded observer assessed the onset time, block-related pain scores, and success
      rate (surgical anesthesia). The main outcome variable was the total anesthesia
      related time (sum of performance and onset times). RESULTS: No differences were
      observed between the 2 groups in terms of success rate (92%-96%), total
      anesthesia-related time (27.1-29.0 min), and block-related pain scores. However,
      the PV technique required fewer needle passes (3.5 [SD, 1.0] vs 8.2 [SD, 2.2]; P
      = 0.000) as well as a shorter performance time (8.2 [SD, 2.3] vs 15.7 [SD, 3.2]
      min; P = 0.000) and was associated with a lower incidence of paresthesia (8 vs
      52%; P = 0.001). In contrast, the PN technique resulted in a quicker onset time
      (13.8 [SD, 7.0] vs 18.9 [SD, 7.0] min; P = 0.021) and a decreased incidence of
      vascular puncture (0 vs 24%; P = 0.01). CONCLUSIONS: Perivascular and PN
      ultrasound-guided AXBs result in comparable success rates and total anesthesia
      related times. Because of fewer needle passes and a shorter performance time, the
      PV technique provides a simple alternative for ultrasound-guided AXB.

PMID- 22660485
TI  - Looking into learning:  visuospatial and psychomotor predictors of ultrasound
      guided procedural performance.
AB  - BACKGROUND AND OBJECTIVES: Despite widespread use of ultrasound in regional
      anesthesia, little understanding of the psychomotor and visuospatial skills
      required to achieve and maintain procedural proficiency exists. Despite its
      procedural nature, anesthesiology lags behind other fields in assessing technical
      aptitude among practitioners and trainees. The goals of this study were to
      measure relevant visuospatial and psychomotor aptitudes of anesthesia residents
      in-training and to evaluate the relationship between these skill sets and the
      performance of ultrasound-guided regional anesthesia. METHODS: Forty residents
      from the Mayo Clinic Department of Anesthesiology were enrolled, and 39 (PGY-1
      through PGY-4) voluntarily completed a demographic survey, 4 psychomotor and 4
      visuospatial aptitude assessments, and an ultrasound-based performance
      assessment. RESULTS: The Block Design Test, a subtest of the Wechsler Adult
      Intelligent Scale - III, correlated with ultrasound guided skill performance
      (correlation coefficient, 0.47; P < 0.002). By contrast, psychomotor aptitude
      assessments did not correlate with ultrasound task performance. Psychomotor skill
      performance was significantly reduced by indirect hand-eye coordination visual
      feedback (projected image) compared with direct hand-eye coordination (P <
      0.001). A learning effect was observed between the first and second ultrasound
      skill task attempts and was independent of hand dominance. DISCUSSION: This study
      reveals that visuospatial aptitude is a better predictor of ultrasound-based
      procedural performance than psychomotor ability. The type of real-time visual
      feedback (indirect versus direct) used for hand-eye coordination significantly
      impacts procedural performance and has implications for anesthesia and other
      procedural specialties. The learning effect noted during initial ultrasound skill
      trials suggests visuospatial assimilation and underscores the importance of early
      ultrasound instruction.

PMID- 22660486
TI  - Sciatic nerve block fails in preventing the development of late stress-induced
      hyperalgesia when high-dose fentanyl is administered perioperatively in rats.
AB  - : Sciatic nerve block fails in preventing the development of late stress-induced
      hyperalgesia (SIH) when high-dose fentanyl is administered perioperatively in
      rats. BACKGROUND AND OBJECTIVES: The aim of our study was to evaluate the effect
      of regional anesthesia (RA) on hyperalgesia and long-term pain vulnerability
      after surgery in rats exposed or not to high doses of fentanyl intraoperatively.
      METHODS: Experiment 1 evaluated the effects of D0 RA on hyperalgesia after
      incision and on the variations of nociceptive threshold (NT) after non
      nociceptive environmental stress (NNES) at D10. Four groups were compared:
      control K1 (saline in sciatic nerve catheter, no plantar surgery), I (incision:
      saline in sciatic nerve catheter and plantar surgery), ISSR (incision-single-shot
      ropivacaine: single-shot ropivacaine, plantar surgery), and IMSR (incision
      multiple-shot ropivacaine: 1 shot of ropivacaine, plantar surgery, and then 3
      more ropivacaine injections every 2 h). Experiment 2 evaluated the effects of D0
      RA (4 injections) on NT variations after surgery (D1-D10) and after stress (D10)
      in rats treated with fentanyl at the time of surgery (FI and FIMSR groups).
      RESULTS: Postoperative hyperalgesia lasted for 7, 4, and 2 days for groups I,
      ISSR, and IMSR, respectively. Non-nociceptive environmental stress at D10 showed
      analgesia during stress in K1 (Dunnett, P < 0.05). Poststress area of
      hyperalgesia showed that I group developed greater hyperalgesia after NNES than
      ISSR and IMSR did (Mann-Whitney, P < 0.05). In experiment 2 in the FIMSR group,
      NT was significantly higher at postoperative D1 and D2 (Dunnett, P < 0.05), but
      no difference was shown from D3 to D10 (Dunnett, P > 0.05). Hyperalgesic indices
      calculated for FI and FIMSR groups after NNES at D10 did no show any significant
      difference (Dunnett, P > 0.05). CONCLUSIONS: Perioperative use of long-lasting RA
      reduced both acute postoperative hyperalgesia and the development of long-term
      pain vulnerability. However, high doses of fentanyl for intraoperative analgesia
      induce central sensitization that cannot be reversed by using long-lasting RA.

PMID- 22660487
TI  - The definition of block "success" in the contemporary literature: are we speaking
      the same language?
AB  - A successful nerve block is the common goal that shapes modern regional
      anesthesia practice and research, yet the meaning of block "success" can be open
      to interpretation. For this Special Article, we reviewed all applicable
      randomized controlled trials published over the last decade to determine the most
      commonly used definitions of block success. We also sought to uncover which
      relevant indicators of block success are routinely reported in the contemporary
      literature. Twenty-two trials that explicitly designated the term block "success"
      as their primary outcome measure were identified. The most common definition of
      block success was the achievement of a surgical block within a designated period,
      used in half of the trials. Block success was inconsistently defined in the
      remaining 11 trials. Patient-related indicators of block success including
      postoperative pain and patient satisfaction were measured in only 4 trials,
      whereas anesthesiologist-related indicators such as block onset time and
      complications were reported most frequently. Surgeon- and hospital administrator
      related indicators were not collected in any trial. We found that the definition
      of block success is highly variable in the contemporary regional anesthesia
      literature. Our findings underscore the clear and present need for a
      comprehensive definition of block success, whereas future research should
      endeavor to capture the indicators of block success that are important to all key
      perioperative stakeholders.

PMID- 22660488
TI  - Perineural local anesthetic and adjuvant action: the meaning of an ex vivo data
      set for efficacy and safety.

PMID- 22660510
TI  - [Obscure exophthalmus].
AB  - A 63-year-old male patient presented with retrobulbar pressure which had been
      present for 1 year. Contrast-enhanced computed tomography (CT) and magnetic
      resonance imaging (MRI) revealed symmetrical retrobulbar, perivascular and
      retroperitoneal infiltration of soft tissue and also showed cardiac involvement.
      In combination with the histological findings displaying infiltration by foamy
      histiocytes, Erdheim-Chester disease was diagnosed.

PMID- 22660520
TI  - Polymorphism 677C -> T MTHFR gene in Mexican mothers of children with complex
      congenital heart disease.
AB  - Congenital heart defects (CHD) are the third leading cause of death in children
      <1 year of age in Mexico where there is a high prevalence of the 677C -> T
      polymorphism of the MTHFR gene. This is important because the homozygous 677T/T
      MTHFR gene and deficiency of folic acid (FA) intake have been associated with
      CHD. Our objective was to analyze the possible association between the genotype
      677T/T of the MTHFR gene and supplementation of FA in Mexican women with the
      presence of complex CHD in their children. We analyzed genotypes of 31 mothers of
      children with complex CHD (group I) and 62 mothers of healthy children (group II)
      and investigated FA supplementation during pregnancy in both study groups. Allele
      frequencies in group I were 41.9 % for C and 58.1 % for T and 22.6 % for genotype
      frequencies CC, 38.7 % for CT, and 38.7 % for TT. Allele frequencies in group II
      were 63.7 % for C and 36.3 % for T and 38.7 % for genotype frequencies CC, 50 %
      for CT and 11.3 % for TT. Both populations are in Hardy-Weinberg equilibrium.
      Odds ratio for having a child with a complex CHD was 5.9, p = 0.008 (95 % CI
      1.67; 20.63) for the TT genotype. FA supplementation at any time during pregnancy
      was 90.3 and 87.9 % in groups II and I respectively (p > 0.05). Association was
      found between the maternal genotype (677/TT MTHFR) with the presence of complex
      CHD in their offspring. No differences in FA supplementation during any stage
      were found between groups.

PMID- 22660521
TI  - Abnormal mitral valve anatomy in d-transposition of the great arteries: anatomic
      characterization and surgical outcomes.
AB  - Mitral valve anomalies can occur with S,D,D-transposition of the great arteries
      (d-TGA). Their influence on surgical technique and outcome after an arterial
      switch operation (ASO) has not been well described. Patients with d-TGA who
      underwent ASO from February 1990 to January 2011 were identified.
      Echocardiograms, operative reports, hospital course, and latest follow-up
      evaluation were reviewed. A total of 218 infants underwent ASO at a median age of
      15.8 days. Survival was 95 % during a mean follow-up period of 60 months. Nine
      patients (4 %) were found to have similar mitral valve anomalies including
      anterior malalignment conoventricular septal defect, anterior displacement of the
      mitral valve toward the left ventricular outflow tract (LVOT), malpositioning of
      the posteromedial papillary muscle, unusual rotation of the mitral valve leaflets
      orienting the commissure toward the anterior ventricular septum, and redundant
      mitral valve tissue extending into the LVOT. Coarctation was more frequent in
      this subgroup (33 vs. 10 %; p = 0.05). Preoperative echocardiography consistently
      indicated suspicion of a cleft mitral valve with chordal attachments to the
      ventricular septum causing potential LVOT obstruction. Operative inspection did
      not identify a cleft or anomalous attachments in any patient, and no
      valvuloplasty or chordal manipulation was performed. The average hospital length
      of stay were similar (30.7 vs. 25.3 days; p = 0.54). One patient died late due to
      progressive LVOT obstruction, and one required heart transplantation. No patient
      had significant mitral valve regurgitation. We conclude that mitral valve
      anomalies associated with d-TGA are rare but present with consistent anatomic
      features and higher risk of coarctation. Unusual mitral valve apparatus
      positioning and chordal redundancy can suggest the need for valvuloplasty and
      chordal resection preoperatively, but this is rarely needed.

PMID- 22660522
TI  - Left atrial volume change throughout the cardiac cycle in children with
      congenital heart disease associated with increased pulmonary blood flow:
      evaluation using a novel left atrium-tracking method.
AB  - There is a paucity of data regarding the significance of left atrial (LA) volume
      and its changes throughout the cardiac cycle in pediatric patients with heart
      disease. The recently developed LA volume-tracking (LAVT) method can
      automatically construct the LA volume curve. The study group consisted of 48
      pediatric patients with ventricular septal defect (n = 34) or patent ductus
      arteriosus (n = 14) and age-matched healthy controls. Maximum and minimum LA
      volumes (LAVmax and LAVmin, respectively) were measured. The total LA emptying
      volume (LAVtotal) was defined as LAVmax--LAVmin. Volume parameters were
      standardized by dividing by body surface area (BSA). The total LA emptying
      fraction (%LAVtotal) was defined as the ratio of LAVtotal to LAVmax. In the
      patient group, there was a positive correlation between the ratio of pulmonary to
      systemic blood flow (Qp/Qs) and LAVmax/BSA, LAVmin/BSA, and LAVtotal/BSA (r =
      0.42, 0.44, and 0.34, respectively). LAVmin/BSA was positively correlated with
      the ratio of early mitral inflow velocity to early mitral annular diastolic
      tissue Doppler velocity (E/E') (r = 0.32). The %LAVtotal had a negative
      correlation with left-ventricular (LV) end-diastolic pressure (r = -0.32). There
      were significant correlations between serum B-type natriuretic peptide level and
      LAVmax/BSA, LAVmin/BSA, and %LAVtotal (r = 0.38, 0.49, and -0.35, respectively).
      The LAVT method is useful in the evaluation of LV diastolic function in pediatric
      patients with chronic LV volume overload.

PMID- 22660523
TI  - Interventions after Norwood procedure: comparison of Sano and modified Blalock
      Taussig shunt.
AB  - Improved results have evolved from the modified Norwood procedure (NP). This
      study compares the incidence of interventions after NP with the Sano (n = 37) and
      modified Blalock-Taussig (BT n = 70) shunt. Incidence, location, interval of
      interventions, and weight were retrospectively analysed for 107 neonates
      undergoing NP during the period from October 2002 to December 2009. Forty-six
      (43.0 %) patients underwent interventions, mostly for dilatation of the aortic
      arch ([DAA] n = 26 [24.3 %]; Sano n = 10, BT n = 16, p = 0.6), dilatation of the
      shunt ([DS] n = 15 [14.0 %]; Sano n = 11, BT n = 4; p = 0.002), or closure of
      aortopulmonary collaterals ([APC] n = 15 [14.0 %]; Sano n = 3, BT n = 12; p =
      0.08). Mean interval after NP and body weight at DAA, DS, and APC were 72.4 +/-
      18.9, 108.5 +/- 15.8, and 110.7 +/- 17.8 days and 4.5 +/- 1.3, 4.9 +/- 1.9, 5.3
      +/- 1.2 kg, respectively. The interventions were not associated with mortality
      but with a greater rate of complications (9 of 46 [21.4 %]) compared with the
      rate after diagnostic catheterization (0 of 45, p = 0.03). Complications included
      closure of the femoral or subclavian artery (n = 5), cerebral embolic or bleeding
      events (n = 4), cardiopulmonary resuscitation (n = 3), and temporary heart block
      (n = 2). Actuarial survival was similar from the postoperative month 8 onward at
      78.6 +/- 4.9 % (95 % confidence interval [CI] 67.0-86.5 %) for Sano and 78.4 +/-
      6.8 % (95 % CI 61.4-88.6 %) for BT (p = 0.95). Interventions after NP were common
      irrespective of shunt type. However, a significantly greater rate of shunt
      interventions was noted in the Sano group. In particular, interventions
      addressing the aortic arch and the shunt were related with a significant rate of
      complications.

PMID- 22660524
TI  - Standardizing measures in four domains of employment outcomes for individual
      placement and support.
AB  - OBJECTIVE: Virtually all studies of the individual placement and support (IPS)
      model of supported employment measure outcomes for job acquisition, but studies
      are less consistent in measuring job tenure, hours worked, and employment
      earnings. Lack of a common set of employment measures limits comparisons across
      studies and cumulative knowledge about IPS. To lay the groundwork for
      standardization, this study examined measures in four employment domains and
      their interrelationships. METHODS: Using a combined data set from four randomized
      controlled trials of IPS, this study examined mean differences between IPS
      participants (N=307) and participants in other vocational services (control
      sample) (N=374) in four domains (job acquisition, job duration, hours worked per
      week, and total hours and wages). Eight competitive employment measures were
      examined (employed at any time, total weeks worked, tenure in the longest-held
      job, total hours worked, average hours per week worked, total wages, days to
      first job, and working >= 20 hours per week during follow-up). Correlations
      between measures within both the IPS and control samples were determined.
      RESULTS: IPS participants had significantly better outcomes across all employment
      measures and domains. Correlations between measures were strong within each
      domain, but they were variable between domains. CONCLUSIONS: In addition to
      improving job acquisition, IPS improved job duration, hours worked per week, and
      total hours and wages. The correlational findings suggest proxy measures to
      assist meta-analysts in the synthesis of studies for which direct measures are
      unavailable. Initial steps toward a cross-disciplinary theoretical framework for
      employment outcomes are described.

PMID- 22660525
TI  - Self-assembly and alterable relaxivity of an organic cation-encapsulated
      gadolinium-containing polyoxometalate.
AB  - A new amphiphilic molecule bearing poly(ethylene oxide) (PEO) and quaternary
      ammonium group, was designed and synthesized to encapsulate paramagnetic Gd(III)
      containing polyoxometalate (Gd-POM) through electrostatic interaction for
      obtaining a water-soluble organic-inorganic hybrid building block based on POM.
      The yielding organic cation-encapsulated Gd-POM (OCEP-Gd) complex exhibited water
      solubility and amphiphility, leading to the spontaneous self-assembly into a
      regular vesicular structure with PEO chains towards water phase and POM units
      locating at the middle. The vesicular aggregate which has a regular monolayer
      structure, was further studied by means of dynamic light scattering, transmission
      electron microscopy, and X-ray diffraction. Due to the synergy of different
      building units, the self-assembly of the complexes was demonstrated to be
      efficient to adjust the ability of Gd-POM to accelerate relaxation of water
      proton, which results from the paramagnetic property of Gd-POM, to a large
      extent. The present work provides a new methodology to obtain water-soluble
      hybrid building blocks based on POM, which may generate more hybrid self-assembly
      structures in aqueous solution and further direct POM-based materials towards
      biomedical applications.

PMID- 22660545
TI  - Maize HapMap2 identifies extant variation from a genome in flux.
AB  - Whereas breeders have exploited diversity in maize for yield improvements, there
      has been limited progress in using beneficial alleles in undomesticated
      varieties. Characterizing standing variation in this complex genome has been
      challenging, with only a small fraction of it described to date. Using a
      population genetics scoring model, we identified 55 million SNPs in 103 lines
      across pre-domestication and domesticated Zea mays varieties, including a
      representative from the sister genus Tripsacum. We find that structural
      variations are pervasive in the Z. mays genome and are enriched at loci
      associated with important traits. By investigating the drivers of genome size
      variation, we find that the larger Tripsacum genome can be explained by
      transposable element abundance rather than an allopolyploid origin. In contrast,
      intraspecies genome size variation seems to be controlled by chromosomal knob
      content. There is tremendous overlap in key gene content in maize and Tripsacum,
      suggesting that adaptations from Tripsacum (for example, perennialism and frost
      and drought tolerance) can likely be integrated into maize.

PMID- 22660546
TI  - Comparative population genomics of maize domestication and improvement.
AB  - Domestication and plant breeding are ongoing 10,000-year-old evolutionary
      experiments that have radically altered wild species to meet human needs. Maize
      has undergone a particularly striking transformation. Researchers have sought for
      decades to identify the genes underlying maize evolution, but these efforts have
      been limited in scope. Here, we report a comprehensive assessment of the
      evolution of modern maize based on the genome-wide resequencing of 75 wild,
      landrace and improved maize lines. We find evidence of recovery of diversity
      after domestication, likely introgression from wild relatives, and evidence for
      stronger selection during domestication than improvement. We identify a number of
      genes with stronger signals of selection than those previously shown to underlie
      major morphological changes. Finally, through transcriptome-wide analysis of gene
      expression, we find evidence both consistent with removal of cis-acting variation
      during maize domestication and improvement and suggestive of modern breeding
      having increased dominance in expression while targeting highly expressed genes.

PMID- 22660547
TI  - Genome-wide genetic changes during modern breeding of maize.
AB  - The success of modern maize breeding has been demonstrated by remarkable
      increases in productivity over the last four decades. However, the underlying
      genetic changes correlated with these gains remain largely unknown. We report
      here the sequencing of 278 temperate maize inbred lines from different stages of
      breeding history, including deep resequencing of 4 lines with known pedigree
      information. The results show that modern breeding has introduced highly dynamic
      genetic changes into the maize genome. Artificial selection has affected
      thousands of targets, including genes and non-genic regions, leading to a
      reduction in nucleotide diversity and an increase in the proportion of rare
      alleles. Genetic changes during breeding happen rapidly, with extensive variation
      (SNPs, indels and copy-number variants (CNVs)) occurring, even within identity-by
      descent regions. Our genome-wide assessment of genetic changes during modern
      maize breeding provides new strategies as well as practical targets for future
      crop breeding and biotechnology.

PMID- 22660548
TI  - The beet R locus encodes a new cytochrome P450 required for red betalain
      production.
AB  - Anthocyanins are red and violet pigments that color flowers, fruits and epidermal
      tissues in virtually all flowering plants. A single order, Caryophyllales,
      contains families in which an unrelated family of pigments, the betalains, color
      tissues normally pigmented by anthocyanins. Here we show that CYP76AD1 encoding a
      novel cytochrome P450 is required to produce the red betacyanin pigments in
      beets. Gene silencing of CYP76AD1 results in loss of red pigment and production
      of only yellow betaxanthin pigment. Yellow betalain mutants are complemented by
      transgenic expression of CYP76AD1, and an insertion in CYP76AD1 maps to the R
      locus that is responsible for yellow versus red pigmentation. Finally, expression
      of CYP76AD1 in yeast verifies its position in the betalain biosynthetic pathway.
      Thus, this cytochrome P450 performs the biosynthetic step that provides the cyclo
      DOPA moiety of all red betacyanins. This discovery will contribute to our ability
      to engineer this simple, nutritionally valuable pathway into heterologous
      species.

PMID- 22660549
TI  - Safety profile and outcome of mild therapeutic hypothermia in patients following
      cardiac arrest: systematic review and meta-analysis.
AB  - Evidence has shown that mild therapeutic hypothermia (MTH) could improve survival
      and neurological outcome in patients following cardiac arrest. But this therapy
      may cause some adverse effects. The authors sought to take a systematic approach
      to describe the safety aspects and outcome of MTH following cardiac arrest to
      help clinical practice. MEDLINE, EMBASE, the Cochrane Central Register of
      Controlled Trials, BIOSIS Previews and clinicaltrials.gov were searched up to
      June 2011. Bibliographies of relevant studies were also reviewed. Comparative
      studies reporting the mortality or any other studies reporting any kind of
      adverse events in patients undergoing MTH after cardiac arrest and published in
      English were included. Of 1742 abstracts, 63 studies were included. Most adverse
      events potentially associated with therapeutic hypothermia were not significantly
      different between the hypothermia therapy and the normothermia groups. No
      significant difference was found in the inhospital mortality, bleeding, pneumonia
      and bradycardia events between surface and endovascular-cooled groups in this
      study. Cooling device-related adverse events were generally mild. Serious adverse
      events potentially attributable to therapeutic hypothermia were seldom reported.
      MTH was associated with reduced inhospital mortality, mortality at 1 month and at
      6 months. Evidence about the safety of MTH in children has been limited. These
      results suggest that while it may result in some adverse events, MTH is generally
      safe in patients following cardiac arrest and could improve the short-term and
      long-term survival of comatose patients after cardiac arrest. But awareness of
      these adverse events should be kept in mind in clinical practice.

PMID- 22660550
TI  - Calcium-sensing receptor gene polymorphisms in patients with calcium
      nephrolithiasis.
AB  - PURPOSE OF REVIEW: The calcium-sensing receptor gene (CaSR, chr. 3q13.3-21) is a
      candidate to explain nephrolithiasis. This review analyzes the potential role of
      CaSR in lithogenesis according to findings of functional and genetic studies.
      RECENT FINDINGS: CaSR is a cation receptor located in the tubular cell plasma
      membrane. Its activation decreases calcium reabsorption in the ascending limb and
      distal convoluted tubule, but increases phosphate reabsorption in proximal
      tubules and decreases water and proton reabsorption in collecting ducts. Its
      effects in proximal tubules and collecting ducts can limit the calcium phosphate
      precipitation risk induced by the increase in calcium excretion. The
      nonconservative CaSR gene Arg990Gly polymorphism was associated with
      nephrolithiasis and hypercalciuria in different populations. Arg990Gly is located
      on exon 7 and produces a gain of the CaSR function. rs7652589 and rs1501899 were
      also associated with nephrolithiasis in patients with normal citrate excretion.
      These polymorphisms are located in the CaSR gene regulatory region and may modify
      CaSR gene promoter activity. SUMMARY: The activating Arg990Gly polymorphism may
      predispose to nephrolithiasis by increasing calcium excretion. Polymorphisms at
      the regulatory region may predispose to nephrolithiasis by changing tubular
      expression of the CaSR. CaSR genotype may be a marker to identify patients prone
      to develop calcium nephrolithiasis.

PMID- 22660551
TI  - Klotho in health and disease.
AB  - PURPOSE OF REVIEW: The klotho gene was originally identified as a putative aging
      suppressor gene in mice that extended life span when overexpressed and induced a
      premature aging syndrome when disrupted. Subsequently, it became clear that the
      Klotho family of membrane proteins function as obligate co-receptors for
      endocrine fibroblast growth factors (FGFs) that regulate various metabolic
      processes. This review focuses on the Klotho-FGF23 endocrine system that
      maintains phosphate (Pi) homeostasis, and discusses the mechanism of action and
      the potential contribution of Klotho deficiency to acute kidney injury (AKI),
      chronic kidney disease (CKD) and cancer. RECENT FINDINGS: Klotho functions as a
      receptor for the phosphaturic hormone FGF23. Klotho deficiency induces resistance
      to FGF23 and predisposition to Pi retention, which represents a critical feature
      of pathophysiology of CKD. The extracellular domain of Klotho protein is subject
      to ectodomain shedding and released into the blood and urine. Secreted Klotho
      functions as a humoral factor that inhibits AKI, vascular calcification, renal
      fibrosis, and cancer metastasis in an FGF23-independent manner. SUMMARY: Various
      factors that affect Klotho expression have been identified. Prevention of Klotho
      decline and supplementation of Klotho can be a novel therapeutic strategy for
      many age-related diseases.

PMID- 22660552
TI  - Targeting signaling pathways in glomerular diseases.
AB  - PURPOSE OF REVIEW: Podocytes are highly specialized epithelial cells that line
      the urinary surface of the glomerular capillary tuft. Dysfunction or death of
      podocytes impacts glomerular permeability and filtration. Here, we discuss the
      recent findings about the role of specific cell signaling pathways in glomerular
      diseases with an emphasis on the molecules in the podocyte that represent
      candidate therapeutic targets. RECENT FINDINGS: A number of local endogenous
      factors that retard the progression of diabetic nephropathy have recently been
      identified and include angiopoietin-1 (Angpt1), Smad7 and nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2). Calcium-dependent regulation of podocyte
      actin dynamics involving transient receptor potential canonical (TRPC) channels
      and the Rho and Rac small GTPases has been shown to play important functions in
      glomerular health and disease. A central role for mammalian target of rapamycin
      (mTOR) activation in the development of diabetic nephropathy and regulation of
      autophagic flux in podocytes during aging has been demonstrated. Discovery of a
      circulating factor (suPAR) that can modulate outside-in beta3 integrin signaling
      in recurrent focal segmental glomerulosclerosis provides exciting therapeutic
      possibilities. Another secreted factor, the hyposialylated form of angiopoietin
      like-protein 4 (ANGPTL4) was found to favor albuminuria in rats and in minimal
      change disease. Therapeutic sialylation of ANGPTL4 could limit albuminuria.
      Finally, neutralization of de novo paracrine activation of glomerular epithelial
      cells by heparin-binding epidermal growth factor (EGF)-like growth factor or EGF
      receptor antagonists could limit crescent formation and renal failure in immune
      mediated vasculitis. SUMMARY: Here, we review the recent developments in our
      understanding of signaling pathways required for podocyte function in health and
      disease. Manipulation of these pathways provides an attractive therapeutic option
      for glomerular diseases.

PMID- 22660554
TI  - Cumulative multiple freeze-thaw cycles and testing does not affect subsequent
      within-day variation in intervertebral flexibility of human cadaveric lumbosacral
      spine.
AB  - STUDY DESIGN: An in vitro biomechanical study on 3-dimensional flexibility of
      human lumbosacral motion segments after multiple freeze-thaw cycles and
      cumulative testing. OBJECTIVE: To determine the significance of multiple freeze
      thaw cycles and extended testing duration on between-day and within-day
      variations in motion segment flexibility. SUMMARY OF BACKGROUND DATA: Previous
      studies have found no significant effect of single freeze-thaw cycle on creep
      behavior of human spinal motion segments. Up to 3 freeze-thaw cycles were found
      to not affect flexibility of porcine spines and viscoelastic properties of human
      tendons, but more than 5 freeze-thaw cycles resulted in declined structural
      properties of human tendons. METHODS: Three lumbosacral motion segments were
      subjected to repeated flexibility tests to determine both the effects of within
      day ambient exposure and between-day multiple freeze-thaw cycles on range of
      motion (ROM) and neutral zone (NZ). Repeated measures analysis of variance was
      carried out to evaluate within-day and between-day effects at alpha = .05.
      RESULTS: Significant between-day effects were found for intervertebral ROM and NZ
      in flexion-extension (FE), lateral bending (LB), and axial rotation (AR) (all P <
      0.001). Post hoc analysis indicated that significant differences from test day 1
      become apparent after 4 freeze-thaw cycles with cumulative testing. There were no
      within-day variations from repeated testing on intervertebral FE ROM (P = 0.10),
      LB ROM (P = 0.36), AR ROM (P = 0.46), FE NZ (P = 0.83), LB NZ (P = 0.42), and AR
      NZ (P = 0.72). CONCLUSION: The flexibility of the human cadaveric lumbosacral
      motion segments between test days was significantly affected after repeated
      freeze-thaw and cumulative testing cycles. Multiple freeze-thaw cycles and
      cumulative testing, however, does not affect flexibility data for tests carried
      out within a single test day.

PMID- 22660558
TI  - [Complexity level simulation in the German diagnosis-related groups system: the
      financial effect of coding of comorbidity diagnostics in urology].
AB  - BACKGROUND: Precise and complete coding of diagnoses and procedures is of value
      for optimizing revenues within the German diagnosis-related groups (G-DRG)
      system. The implementation of effective structures for coding is cost-intensive.
      The aim of this study was to prove whether higher costs can be refunded by
      complete acquisition of comorbidities and complications. METHODS: Calculations
      were based on DRG data of the Department of Urology, University Hospital of
      Munster, Germany, covering all patients treated in 2009. The data were regrouped
      and subjected to a process of simulation (increase and decrease of patient
      clinical complexity levels, PCCL) with the help of recently developed software.
      RESULTS: In urology a strong dependency of quantity and quality of coding of
      secondary diagnoses on PCCL and subsequent profits was found. Departmental
      budgetary procedures can be optimized when coding is effective. The new
      simulation tool can be a valuable aid to improve profits available for
      distribution. Nevertheless, calculation of time use and financial needs by this
      procedure are subject to specific departmental terms and conditions. CONCLUSIONS:
      Completeness of coding of (secondary) diagnoses must be the ultimate
      administrative goal of patient case documentation in urology.

PMID- 22660553
TI  - Shiga toxin-associated hemolytic uremic syndrome:  advances in pathogenesis and
      therapeutics.
AB  - PURPOSE OF REVIEW: Diarrhea-associated hemolytic uremic syndrome (HUS) caused by
      Shiga toxin-producing Escherichia coli (STEC) continues to be an important public
      health threat worldwide. Specific therapies are lacking and patient care remains
      largely supportive. This review discusses the lessons learned from recent events
      and summarizes key advances made toward understanding the basic mechanisms
      involved in the pathogenesis of typical HUS. RECENT FINDINGS: The recent German
      outbreak of a hybrid organism resulted in an unprecedented number of HUS cases
      and drastically changed the face of typical (diarrhea-associated) HUS. New
      findings on the roles of complement and the CXCR4/SDF-1 pathway in HUS
      pathogenesis are summarized and novel therapeutic strategies are highlighted.
      SUMMARY: A better understanding of STEC-mediated HUS underlies improved
      therapeutic approaches. New studies of the mechanistic basis of the disease,
      together with patient-based studies, have led to key findings with important
      clinical implications.

PMID- 22660578
TI  - Scaphoid fracture in a patient after a fall.
AB  - The patient was a 27-year-old man who was referred to a physical therapist
      because of persistent right wrist pain after a fall on an outstretched hand in a
      remote setting 3 months prior. Immediately after the injury, the patient was seen
      by a physician's assistant in a remote medical clinic, where right wrist
      radiographs were completed and interpreted as normal. Based on the history and
      physical exam, a potential scaphoid fracture was suspected. Therefore, the
      physical therapist ordered radiographs of the right wrist, which revealed a
      fracture through the waist of the right scaphoid with a band-like lucency.

PMID- 22660579
TI  - Photocrosslinkable pMHC monomers stain T cells specifically and cause ligand
      bound TCRs to be 'preferentially' transported to the cSMAC.
AB  - The binding of T cell antigen receptors (TCRs) to specific complexes of peptide
      and major histocompatibility complex (pMHC) is typically of very low affinity,
      which necessitates the use of multimeric pMHC complexes to label T lymphocytes
      stably. We report here the development of pMHC complexes able to be crosslinked
      by ultraviolet irradiation; even as monomers, these efficiently and specifically
      stained cognate T cells. We also used this reagent to probe T cell activation and
      found that a covalently bound pMHC was more stimulatory than an agonist pMHC on
      lipid bilayers. This finding suggested that serial engagement of TCRs is
      dispensable for activation when a substantial fraction of TCRs are stably
      engaged. Finally, pMHC-bound TCRs were 'preferentially' transported into the
      central supramolecular activation cluster after activation, which suggested that
      ligand engagement enabled linkage of the TCR and its associated CD3 signaling
      molecules to the cytoskeleton.

PMID- 22660580
TI  - F-box protein FBXL19-mediated ubiquitination and degradation of the receptor for
      IL-33 limits pulmonary inflammation.
AB  - The ST2L receptor for interleukin 33 (IL-33) mediates pulmonary inflammation and
      immune system-related disorders, such as asthma and rheumatoid arthritis. At
      present, very little is known about the molecular regulation of ST2L expression.
      Here we found that FBXL19, an 'orphan' member of the Skp1-Cullin-F-box family of
      E3 ubiquitin ligases, selectively bound to ST2L to mediate its polyubiquitination
      and elimination in the proteasome. Degradation of ST2L involved phosphorylation
      of ST2L at Ser442 catalyzed by the kinase GSK3beta. Overexpression of FBXL19
      abrogated the proapoptotic and inflammatory effects of IL-33 and lessened the
      severity of lung injury in mouse models of pneumonia. Our results suggest that
      modulation of the IL-33-ST2L axis by ubiquitin ligases might serve as a unique
      strategy for lessening pulmonary inflammation.

PMID- 22660581
TI  - Cervical cancer screening and acute care visits among Medicaid enrollees with
      mental and substance use disorders.
AB  - OBJECTIVE: This study compared rates of cervical cancer screening and acute care
      (primary or gynecological) visits among women with and without a diagnosis of
      psychosis, substance use disorder, bipolar disorder or mania, or depression.
      METHODS: Using data about women (N=105,681) enrolled in Maryland's Medicaid
      program in fiscal year 2005, the authors constructed logistic models with cancer
      screening and acute care visits as dependent variables and serious mental illness
      flags as independent variables. Covariates were age, race, geography, Medicaid
      eligibility category, and sexually transmitted diseases. The logistic model of
      cervical cancer screening outcomes was repeated with acute care visits as a
      covariate. RESULTS: Women with psychosis (N=4,747), bipolar disorder or mania
      (N=3,319), or depression (N=5,014) were significantly (p<.05) more likely than
      women in a control group without such disorders (N=85,375) to receive cancer
      screening (adjusted odds ratio (AOR) range=1.46-1.78) and to have associated
      acute care visits (AOR range=1.45-2.15). Compared with those in the control
      group, women with a substance use disorder, with (N=1,104) or without (N=6,122)
      psychosis, demonstrated reduced odds of cancer screening (AOR=.80) but similar
      odds of acute care visits (AOR=1.04). Acute care visits were strongly correlated
      with cancer screens. Genital cancer prevalence did not significantly differ among
      diagnostic groups. CONCLUSIONS: In Maryland Medicaid, the odds of cancer
      screening and related acute care visits were greater for women with major mental
      disorders compared with women in the control group. For women with substance use
      disorders, however, screening was reduced and acute care visits were similar
      compared with women in the control group. Providers should encourage and support
      their patients with substance use disorders to increase use of preventive care
      services by primary care physicians and gynecologists.

PMID- 22660604
TI  - Critical illness is a major determinant of midazolam clearance in children aged 1
      month to 17 years.
AB  - BACKGROUND: In children, a large variability in pharmacokinetics of midazolam, a
      cytochrome P450 3A4/5 (CYP3A4/5) enzyme substrate, has been described, which
      cannot be explained by age-related changes alone. In this study, these age
      related changes are studied in relation to other covariates to explain the
      variability in the pharmacokinetics of midazolam in children. METHODS: Population
      pharmacokinetic modeling was performed using a joint dataset of 3 studies
      conducted previously: study 1: pediatric intensive care patients requiring
      sedation in the intensive care unit; study 2: pediatric oncology patients
      undergoing an invasive procedure; study 3: otherwise healthy infants admitted for
      postoperative monitoring after elective major craniofacial surgery. Midazolam, 1
      hydroxymidazolam, and 1-hydroxymidazolam glucuronide concentrations were
      considered to determine the pharmacokinetics of midazolam and metabolites using
      NONMEM 6.2. SimCYP pediatric simulator was used for simulation. RESULTS: Fifty
      four children aged between 1 month and 17 years who received intravenous
      midazolam (bolus and/or continuous infusion) for sedation were included in this
      study. A reduction of 93% for CYP3A4/5 (midazolam to 1-hydroxymidazolam) and 86%
      for uridine diphosphate glucuronosyltransferase (1-hydroxymidazolam to 1
      hydroxymidazolam glucuronide) mediated clearance was found in pediatric intensive
      care patients compared with the other 2 patient groups. We did not find a
      significant influence of age or bodyweight on CYP3A4/5-mediated total clearance.
      For uridine diphosphate glucuronosyltransferase-mediated clearance, bodyweight
      explained 41.5% of the variability. CONCLUSIONS: From infancy to adolescence,
      critical illness seems to be a major determinant of midazolam clearance, which
      may result from reduced CYP3A4/5 activity due to inflammation. This may have
      important implications for dosing of midazolam and other CYP3A drug substrates in
      critically ill children.

PMID- 22660605
TI  - Minimization of the preanalytical error in pharmacokinetic analyses and
      therapeutic drug monitoring: focus on IV drug administration.
AB  - BACKGROUND: The conduct of multicenter pharmacokinetic (PK) analyses for long
      established drugs entails specific problems, because samples have to be obtained
      within daily clinical practice. Practices for intravenous (IV) drug
      administration vary between hospitals, including the use of different infusion
      devices, the use of infusion line systems with different line volumes, and
      different priming and rinsing procedures. METHODS: Variables of IV drug
      administration that could influence concentration data obtained in PK analyses
      were evaluated. Kinetics of drug delivery during initiation and cessation of IV
      infusions were simulated in vitro for a drop-counter and a syringe-driven
      infusion system at different flow rates. Furthermore, the percentages of the
      target drug dosage remaining in the infusion line after different rinsing periods
      were investigated in vitro and in clinical practice. RESULTS: Varying times
      required for the drug to migrate from the bag/syringe to the cannula and to reach
      a steady-state drug administration rate were observed. Time to steady state
      ranged from almost immediate to 48 minutes depending on the infusion system and
      flow rate. The longest times were seen for the drop-counter system at low flow
      rates and were associated with large drug concentration gradients in the infusion
      line, which makes it difficult to accurately determine start and end of the
      infusion. For most systems, when rinsing at the end of infusion was performed
      with once the volume of the infusion line, <5% of the total drug dosage was
      discarded. Larger variability was seen for slow infusion rates and small infusion
      volumes. CONCLUSIONS: The choice of the infusion apparatus, standardized infusion
      systems, and standardized operating procedures for drug administration are
      important when performing postmarketing PK analyses in multicentric studies.

PMID- 22660606
TI  - Expression of Monstera deliciosa agglutinin gene (mda) in tobacco confers
      resistance to peach-potato aphids.
AB  - The aphid is one of the most serious pests that causes damage to crops worldwide.
      Lectins from Araceae plant had been proved useful to control the aphid. Herein,
      the full-length cDNA of Monstera deliciosa agglutinin (mda) gene was cloned and
      then introduced into tobacco and the influence of the expression of mda in
      transgenic tobacco against peach-potato aphids (Myzus persicae) was investigated.
      Among 92 regenerated plants, 59 positive tobacco lines were obtained. Real-time
      PCR assays and aphid bioassay test revealed that there is a positive correlation
      between the expression level of mda and the inhibitory effect on peach-potato
      aphids. The average anti-pests ability of mda transgenic tobacco was 74%, which
      was higher than that of other reported lectins from Araceae plant. These results
      indicated that MDA is one of promising insect resistance proteins selected for
      the control of peach-potato aphids.

PMID- 22660623
TI  - Acetate regulation of spore formation is under the control of the Ras/cyclic
      AMP/protein kinase A pathway and carbon dioxide in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, the Ras/cyclic AMP (cAMP)/protein kinase A (PKA)
      pathway is a nutrient-sensitive signaling cascade that regulates vegetative
      growth, carbohydrate metabolism, and entry into meiosis. How this pathway
      controls later steps of meiotic development is largely unknown. Here, we have
      analyzed the role of the Ras/cAMP/PKA pathway in spore formation by the meiosis
      specific manipulation of Ras and PKA or by the disturbance of cAMP production. We
      found that the regulation of spore formation by acetate takes place after
      commitment to meiosis and depends on PKA and appropriate A kinase activation by
      Ras/Cyr1 adenylyl cyclase but not by activation through the Gpa2/Gpr1 branch. We
      further discovered that spore formation is regulated by carbon
      dioxide/bicarbonate, and an analysis of mutants defective in acetate transport
      (ady2Delta) or carbonic anhydrase (nce103Delta) provided evidence that these
      metabolites are involved in connecting the nutritional state of the meiotic cell
      to spore number control. Finally, we observed that the potential PKA target Ady1
      is required for the proper localization of the meiotic plaque proteins Mpc70 and
      Spo74 at spindle pole bodies and for the ability of these proteins to initiate
      spore formation. Overall, our investigation suggests that the Ras/cAMP/PKA
      pathway plays a crucial role in the regulation of spore formation by acetate and
      indicates that the control of meiotic development by this signaling cascade takes
      places at several steps and is more complex than previously anticipated.

PMID- 22660625
TI  - Ultrasound assessment of an acute biceps brachii injury.
AB  - The patient was a 24-year-old woman who was evaluated by a physical therapist in
      a direct-access sports medicine clinic for a chief complaint of right anterior
      arm pain and swelling. Given the unusual mechanism and location of the injury,
      significant pain and weakness, and questionable tissue defect, diagnostic
      ultrasound was ordered. The ultrasound examination findings revealed a strain of
      the right short head of the biceps brachii with a partial tear more distally.

PMID- 22660624
TI  - Solubility-promoting function of Hsp90 contributes to client maturation and
      robust cell growth.
AB  - The Hsp90 chaperone is required for the maturation of signal transduction
      clients, including many kinases and nuclear steroid hormone receptors. The
      binding and hydrolysis of ATP by Hsp90 drive conformational rearrangements in
      three structure domains. Two intrinsically disordered regions of Hsp90 located
      between these domains and at the C terminus have traditionally been considered to
      impart flexibility. We discovered that the charged nature of these acid-rich
      disordered regions imparts a solubility-promoting function to Hsp90 that is
      important for its cellular activity in yeast. Both the solubility-promoting
      function and ATPase activity must occur in the same Hsp90 molecule in order to
      support robust growth, suggesting that the solubility-promoting function is
      required during the ATP-driven client maturation process. Expression of model
      clients together with Hsp90 variants indicated interdependent solubilities
      mediated by the aggregation propensities of both the client and Hsp90. We propose
      a model whereby the charge-rich disordered regions of Hsp90 serve a solubility
      promoting function important for complexes with aggregation-prone clients. These
      findings demonstrate a novel biological function of the intrinsically disordered
      regions in Hsp90 and provide a compelling rationale for why their charged
      properties are conserved throughout eukaryotic evolution.

PMID- 22660629
TI  - Genetic analysis and molecular mapping of a new powdery mildew resistant gene
      Pm46 in common wheat.
AB  - Powdery mildew (PM), caused by Blumeria graminis f. sp. tritici (Bgt), has become
      a serious disease and caused severe yield losses in the wheat production
      worldwide. Resistance gene(s) in wheat cultivars can be quickly overcome by newly
      evolved pathogen races when these genes are employed for long time or in a large
      area. It is urgent to search for new sources of resistance to be used in wheat
      breeding. Tabasco is a German resistant cultivar and a new source of resistance
      gene(s) to PM. An F(2) population was developed from a cross between Tabasco and
      a Chinese susceptible cultivar Ningnuo 1. Infection types in 472 F(2) plants and
      436 F(2-3) families were evaluated by inoculating plants with isolate Bgt19.
      Results showed that a single dominant gene, designed Pm46, controlled powdery
      mildew resistance in Tabasco. This gene was located to the short arm of
      chromosome 5D (5DS) and flanked by simple sequence repeat markers Xgwm205 and
      Xcfd81 at 18.9 cM apart. Because another resistance gene Pm2 was also located on
      5DS, 15 Bgt isolates were used to inoculate Tabasco and Ulka/8*Cc (Pm2 carrier).
      The results showed that Tabasco was highly resistant to all of the 15 isolates
      tested, while Ulka/8*Cc was susceptible to 4 of the isolates, suggesting that
      Tabasco may carry resistant gene(s) different from Pm2 gene in Ulka/8*Cc. To test
      the allelism between Pm46 and Pm2, an F(2) population between Tabasco and
      Ulka/8*Cc was developed. Isolate Bgt2, avirulent to both parents, was used to
      evaluate the F(2) population and two susceptible plants were identified from 536
      progenies with F(2) plants. This result indicated that Pm46 is not allelic to
      Pm2. Therefore, Pm46 is a new gene for PM resistance identified in this study.

PMID- 22660630
TI  - Hybridization between crops and wild relatives: the contribution of cultivated
      lettuce to the vigour of crop-wild hybrids under drought, salinity and nutrient
      deficiency conditions.
AB  - With the development of transgenic crop varieties, crop-wild hybridization has
      received considerable consideration with regard to the potential of transgenes to
      be transferred to wild species. Although many studies have shown that crops can
      hybridize with their wild relatives and that the resulting hybrids may show
      improved fitness over the wild parents, little is still known on the genetic
      contribution of the crop parent to the performance of the hybrids. In this study,
      we investigated the vigour of lettuce hybrids using 98 F(2:3) families from a
      cross between cultivated lettuce and its wild relative Lactuca serriola under non
      stress conditions and under drought, salinity and nutrient deficiency. Using
      single nucleotide polymorphism markers, we mapped quantitative trait loci
      associated with plant vigour in the F(2:3) families and determined the allelic
      contribution of the two parents. Seventeen QTLs (quantitative trait loci)
      associated with vigour and six QTLs associated with the accumulation of ions
      (Na(+), Cl(-) and K(+)) were mapped on the nine linkage groups of lettuce. Seven
      of the vigour QTLs had a positive effect from the crop allele and six had a
      positive effect from the wild allele across treatments, and four QTLs had a
      positive effect from the crop allele in one treatment and from the wild allele in
      another treatment. Based on the allelic effect of the QTLs and their location on
      the genetic map, we could suggest genomic locations where transgene integration
      should be avoided when aiming at the mitigation of its persistence once crop-wild
      hybridization takes place.

PMID- 22660631
TI  - The contribution of intersubspecific hybridization to the breeding of super-high
      yielding japonica rice in northeast China.
AB  - Hybridization between indica and japonica rice combined with utilization of ideal
      plant type has led to the development of high-yielding japonica rice in northern
      China. However, the contribution at the genomic level of intersubspecific
      hybridization to the increased yield of northern Chinese japonica rice is
      uncertain. In this study, we analyzed the genomic pedigree of descendants of
      hybridization between indica and japonica rice grown in northeastern China
      between 1963 and 2008. Simple sequence repeat markers indicated that since 1990
      the genetic diversity among northern japonica cultivars was enriched. Genome-wide
      analysis with subspecies-specific indel and intron length polymorphism markers
      showed indica-allele frequencies were significantly increased in cultivars bred
      after 1990, and were significantly positively correlated with spikelet number per
      panicle and significantly negatively correlated with panicle number per plant.
      Among eight genes controlling agronomic traits, GN1a and GS3 were partially fixed
      in the genome of northern japonica cultivars. In contrast, Waxy and qSH1 were
      eliminated, whereas DEP1 and qSW5 were retained. Indica germplasm is an important
      contributor to the increased yield of northern japonica rice. Breeding for high
      yield and grain quality in combination is a complicated process and difficult to
      achieve when relying on only one or several functional genes, thus the selection
      expertise of the breeder remains critical.

PMID- 22660634
TI  - A new isoform of steroid receptor coactivator-1 is crucial for pathogenic
      progression of endometriosis.
AB  - Endometriosis is considered to be an estrogen-dependent inflammatory disease, but
      its etiology is unclear. Thus far, a mechanistic role for steroid receptor
      coactivators (SRCs) in the progression of endometriosis has not been elucidated.
      An SRC-1-null mouse model reveals that the mouse SRC-1 gene has an essential role
      in endometriosis progression. Notably, a previously unidentified 70-kDa SRC-1
      proteolytic isoform is highly elevated both in the endometriotic tissue of mice
      with surgically induced endometriosis and in endometriotic stromal cells biopsied
      from patients with endometriosis compared to normal endometrium. Tnf-/- and Mmp9
      /- mice with surgically induced endometriosis showed that activation of tumor
      necrosis factor a (TNF-alpha)-induced matrix metallopeptidase 9 (MMP9) activity
      mediates formation of the 70-kDa SRC-1 C-terminal isoform in endometriotic mouse
      tissue. In contrast to full-length SRC-1, the endometriotic 70-kDa SRC-1 C
      terminal fragment prevents TNF-alpha-mediated apoptosis in human endometrial
      epithelial cells and causes the epithelial-mesenchymal transition and the
      invasion of human endometrial cells that are hallmarks of progressive
      endometriosis. Collectively, the newly identified TNF-alpha-MMP9-SRC-1 isoform
      functional axis promotes pathogenic progression of endometriosis.

PMID- 22660635
TI  - The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by
      targeting TAB2, TAB3 and IKK-alpha.
AB  - Inflammatory cytokines such as interleukin-17 (IL-17) promote inflammatory
      autoimmune diseases. Although several microRNAs (miRNAs) have been shown to
      regulate autoimmune pathogenesis by affecting lymphocyte development and
      function, the role of miRNAs in resident cells present in inflammatory lesions
      remains unclear. Here we show that miR-23b is downregulated in inflammatory
      lesions of humans with lupus or rheumatoid arthritis, as well as in the mouse
      models of lupus, rheumatoid arthritis or multiple sclerosis. IL-17 downregulates
      miR-23b expression in human fibroblast-like synoviocytes, mouse primary kidney
      cells and astrocytes and is essential for the downregulation of miR-23b during
      autoimmune pathogenesis. In turn, miR-23b suppresses IL-17-, tumor necrosis
      factor alpha (TNF-alpha)- or IL-1beta-induced NF-kappaB activation and
      inflammatory cytokine expression by targeting TGF-beta-activated kinase 1/MAP3K7
      binding protein 2 (TAB2), TAB3 and inhibitor of nuclear factor kappa-B kinase
      subunit alpha (IKK-alpha) and, consequently, represses autoimmune inflammation.
      Thus, IL-17 contributes to autoimmune pathogenesis by suppressing miR-23b
      expression in radio-resident cells and promoting proinflammatory cytokine
      expression.

PMID- 22660643
TI  - Acoustofluidics 13: Analysis of acoustic streaming by perturbation methods.
AB  - In this Part 13 of the tutorial series "Acoustofluidics--exploiting ultrasonic
      standing waves forces and acoustic streaming in microfluidic systems for cell and
      particle manipulation," the streaming phenomenon is presented from an analytical
      standpoint, and perturbation methods are developed for analyzing such flows.
      Acoustic streaming is the phenomenon that takes place when a steady flow field is
      generated by the absorption of an oscillatory field. This can happen either by
      attenuation (quartz wind) or by interaction with a boundary. The latter type of
      streaming can also be generated by an oscillating solid in an otherwise still
      fluid medium or vibrating enclosure of a fluid body. While we address the first
      kind of streaming, our focus is largely on the second kind from a practical
      standpoint for application to microfluidic systems. In this Focus article, we
      limit the analysis to one- and two-dimensional problems in order to understand
      the analytical techniques with examples that most-easily illustrate the streaming
      phenomenon.

PMID- 22660636
TI  - Viral delivery of miR-196a ameliorates the SBMA phenotype via the silencing of
      CELF2.
AB  - Spinal and bulbar muscular atrophy (SBMA) is an inherited neurodegenerative
      disorder caused by the expansion of the polyglutamine (polyQ) tract of the
      androgen receptor (AR-polyQ). Characteristics of SBMA include proximal muscular
      atrophy, weakness, contraction fasciculation and bulbar involvement. MicroRNAs
      (miRNAs) are a diverse class of highly conserved small RNA molecules that
      function as crucial regulators of gene expression in animals and plants. Recent
      functional studies have shown the potent activity of specific miRNAs as disease
      modifiers both in vitro and in vivo. Thus, potential therapeutic approaches that
      target the miRNA processing pathway have recently attracted attention. Here we
      describe a novel therapeutic approach using the adeno-associated virus (AAV)
      vector-mediated delivery of a specific miRNA for SBMA. We found that miR-196a
      enhanced the decay of the AR mRNA by silencing CUGBP, Elav-like family member 2
      (CELF2). CELF2 directly acted on AR mRNA and enhanced the stability of AR mRNA.
      Furthermore, we found that the early intervention of miR-196a delivered by an AAV
      vector ameliorated the SBMA phenotypes in a mouse model. Our results establish
      the proof of principle that disease-specific miRNA delivery could be useful in
      neurodegenerative diseases.

PMID- 22660659
TI  - Alemtuzumab induction therapy in kidney transplantation: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Alemtuzumab (MabCampath or Campath; Genzyme, Cambridge, MA) is a CD52
      specific monoclonal antibody that causes profound and sustained lymphocyte
      depletion. Its use as an induction therapy in organ transplantation is
      increasing. Since our last systematic review in 2006, where we identified the
      need for good-quality randomized controlled trials (RCTs), several RCTs have been
      published that examine its efficacy and safety in kidney transplantation. The aim
      of this study was to evaluate the current evidence for alemtuzumab induction
      therapy in kidney transplantation. METHODS: We performed a systematic literature
      search using Ovid MEDLINE, Embase, Cochrane Central Register of Controlled
      Trials, Transplant Library from the Centre for Evidence in Transplantation, and
      International Clinical Trials Registry Platform. Inclusion criteria specified all
      RCTs in which kidney transplant recipients receiving induction with alemtuzumab
      were compared with those receiving another induction agent or no induction.
      Studies were assessed for methodological quality. The primary outcome was the
      incidence of biopsy-proven acute rejection (BPAR) (Banff grade >=1), and
      secondary outcomes included graft loss, renal function, delayed graft function
      (DGF), patient death, and the incidence of infection, autoimmunity, malignancy,
      and new-onset diabetes mellitus after transplantation. RESULTS: Ten RCTs, with a
      total of 1223 patients, were included. Studies were grouped according to
      induction regimens. Alemtuzumab induction has a lower risk of BPAR compared with
      induction with the interleukin-2 receptor antibodies (IL-2RAs): basiliximab
      (Simulect; Novartis, Basel, Switzerland) and daclizumab (Zenapax; Roche, Basel,
      Switzerland) combined (relative risk, 0.54; 95% confidence interval, 0.37-0.79;
      P<0.01). No significant difference was observed in the risk of BPAR when
      alemtuzumab induction was compared with rabbit antithymocyte globulin (rATG)
      (Thymoglobulin [Genzyme] or ATG-Fresenius S [Fresenius, Munich, Germany])
      (relative risk, 0.79; 95% confidence interval, 0.52-1.21; P=0.28). There was no
      difference in graft loss, DGF, patient death, and new-onset diabetes mellitus
      after transplantation when alemtuzumab was compared with IL-2RAs or rATG
      induction. The effect of alemtuzumab induction on renal function and the
      incidence of infection, malignancy, and autoimmunity were limited by the data
      available. There were two trials comparing alemtuzumab with no induction, but
      neither trial reported a significant reduction in BPAR at 12 months. CONCLUSIONS:
      Alemtuzumab induction reduces the risk of BPAR compared with IL-2RAs but not
      rATG. Because the incidence of other efficacy outcomes (graft loss, DGF, and
      patient death) was similar, if it is felt that an induction agent is necessary,
      then our analysis suggests that it is more acceptable to base the choice of
      induction agent on safety outcomes and/or costs.

PMID- 22660660
TI  - Patellofemoral pain: proximal, distal, and local factors, 2nd International
      Research Retreat.
AB  - Patellofemoral pain (PFP) is one of the most common lower extremity conditions
      seen in orthopaedic practice. The mission of the second International
      Patellofemoral Pain Research Retreat was to bring together scientists and
      clinicians from around the world who are conducting research aimed at
      understanding the factors that contribute to the development and, consequently,
      the treatment of PFP. The format of the 2.5-day retreat included 2 keynote
      presentations, interspersed with 6 podium and 4 poster sessions. An important
      element of the retreat was the development of consensus statements that
      summarized the state of the research in each of the 4 presentation categories. In
      this supplement, you will find the consensus documents from the meeting, as well
      as the keynote addresses, schedule, and platform and poster presentation
      abstracts.

PMID- 22660649
TI  - Use of X-ray scattering to aid the design and delivery of membrane-active drugs.
AB  - Biological membranes can be targets for compounds that either disrupt their
      barrier function or affect protein function via membrane-mediated processes.
      Biophysical studies on membrane-mimetic systems composed of membrane lipids have
      contributed substantially to our knowledge on the pertaining membrane physics and
      aid the development of membrane-specific drugs. Moreover, lipid membranes and, in
      particular, liposomes are convenient systems for drug delivery. We review some of
      our recent work that demonstrates the applicability of X-ray scattering to
      understanding the molecular mechanisms of drug-membrane interactions. In
      particular we focus on effects of anesthetics, sphingomyelinase, and
      antimicrobial peptides. We further discuss X-ray scattering as a quality-control
      tool for liposomal drug-delivery systems.

PMID- 22660661
TI  - A partially interpenetrated metal-organic framework for selective hysteretic
      sorption of carbon dioxide.
AB  - The selective capture of carbon dioxide in porous materials has potential for the
      storage and purification of fuel and flue gases. However, adsorption capacities
      under dynamic conditions are often insufficient for practical applications, and
      strategies to enhance CO(2)-host selectivity are required. The unique partially
      interpenetrated metal-organic framework NOTT-202 represents a new class of
      dynamic material that undergoes pronounced framework phase transition on
      desolvation. We report temperature-dependent adsorption/desorption hysteresis in
      desolvated NOTT-202a that responds selectively to CO(2). The CO(2) isotherm shows
      three steps in the adsorption profile at 195 K, and stepwise filling of pores
      generated within the observed partially interpenetrated structure has been
      modelled by grand canonical Monte Carlo simulations. Adsorption of N(2), CH(4),
      O(2), Ar and H(2) exhibits reversible isotherms without hysteresis under the same
      conditions, and this allows capture of gases at high pressure, but selectively
      leaves CO(2) trapped in the nanopores at low pressure.

PMID- 22660685
TI  - Analysis of correlations between N-terminal pro-B-type natriuretic peptide levels
      and markers of venous pulmonary hypertension in patients referred for heart
      transplantation.
AB  - INTRODUCTION:  Heart failure (HF) is a growing health care problem in the world.
      Secondary pulmonary venous hypertension is usually observed in patients with end
      stage heart failure. OBJECTIVES:  The main purpose of the study was to evaluate
      the relationships between N-terminal pro-B-type natriuretic peptide (NT-proBNP)
      levels and the markers of secondary venous pulmonary   hypertension in patients
      referred for heart transplantation (HTX).  PATIENTS AND METHODS:  This
      retrospective analysis included 35 patients (32 men, 3 women; median age, 55.0;
      interquartile range [IQR] 12.0 years). The study group consisted of all
      consecutive patients referred for HTX, in whom the right-heart catheterization
      using the Swan-Ganz catheter was performed at the same time as the measurement of
      NT-proBNP levels. RESULTS:  A high median value of NT-proBNP (3187.0; IQR 2964.0
      pg/ml) and elevated pulmonary pressure were observed in the study group. There
      was a significant correlation between NT-proBNP levels and the values of
      systolic, mean, and diastolic pulmonary artery pressure (r = 0.5, P = 0.001; r =
      0.5, P = 0.001; r = 0.5, P = 0.002; respectively) as well as cardiac output (r = 
      0.4, P = 0.007). There was also a positive correlation between pulmonary artery
      resistance and NT-proBNP levels (r = 0.5, P = 0.006). CONCLUSIONS:  In our study
      population, the median value of NT-proBNP levels exceeded the normal range 25
      times. There was a correlation between the markers of secondary pulmonary
      hypertension and   cardiac output and NT-proBNP levels. Elevated NT-proBNP levels
      in patients with end-stage HF may be associated with significant secondary venous
      pulmonary hypertension.

PMID- 22660688
TI  - Bleeding risk assessment and management in atrial fibrillation patients. Key
      messages for clinical practice from the European Heart Rhythm Association
      position statement.
AB  - The prevention of thromboembolism is the main therapeutic goal in patients with
      atrial fibrillation (AF). Vitamin K antagonists have been proved highly effective
      in preventing thromboembolic events in patients with AF and despite recent
      advances in oral anticoagulation they remain the most widely used agents.
      Anticoagulation increases the incidence of bleeding; however, in the field of
      stroke prevention in AF the clinical benefit of vitamin K antagonists clearly
      outweighs potential risks. The annual incidence of major bleeding among
      individuals with AF on oral anticoagulation varies widely, ranging from 1.3% to
      7.2%. Several factors affect bleeding risk including the intensity of
      anticoagulation, the efficacy of monitoring modalities, and patient
      characteristics. This multifactorial etiology makes prediction of bleeding risk
      complex, necessitating the derivation and validation of clinical prediction tools
      for the estimation of total bleeding risk in clinical practice. The present
      review summarizes data on definition, risk prediction, prevention, and management
      of oral anticoagulation-associated bleeding as reflected by the recent European
      Heart Rhythm Association consensus statement.

PMID- 22660697
TI  - Voluntary psychiatric emergencies in Los Angeles County after funding of
      California's Mental Health Services Act.
AB  - OBJECTIVE: Since 2006, California's Mental Health Services Act (MHSA) has
      distributed an estimated $6 billion in new tax revenues to county mental health
      systems. Although evaluations of MHSA's effectiveness find favorable outcomes
      among high-risk individuals that represent 6% of all mental health clients, scant
      research has tested whether MHSA funds improve the overall functioning of the
      public mental health system. The authors analyzed whether the incidence of
      voluntary emergency psychiatric visits, a key gauge of the functioning of the
      mental health system, fell below expected levels after the disbursement of MHSA
      funds. Los Angeles County, the most populous county in California, was examined.
      METHODS: The authors obtained the monthly incidence of emergency psychiatric
      visits among Medi-Cal patients for 96 months spanning July 2000 to June 2008 (5.9
      million overall admissions, of which 47,328 were emergency visits). Time-series
      methods controlled for temporal patterns in emergency visits as well as other
      potential confounders (unemployment, for example) that could induce spurious
      associations. RESULTS: The incidence of voluntary psychiatric emergencies fell
      below expected levels eight to 12 months after the disbursement of MHSA funds.
      After one year, emergency visits returned to their long-term mean level. Results
      remained robust after analyses controlled for outliers and potential confounders.
      CONCLUSIONS: In the short term, an infusion of public funds devoted to mental
      health services appeared to reduce psychiatric emergency visits. Explanations for
      the transient nature of the decline in emergency visits in Los Angeles County are
      discussed.

PMID- 22660698
TI  - Differential accumulation of host mRNAs on polyribosomes during obligate pathogen
      plant interactions.
AB  - Plant pathogens elicit dramatic changes in the expression of host genes during
      both compatible and incompatible interactions. Gene expression profiling studies
      of plant-pathogen interactions have only considered messenger RNAs (mRNAs)
      present in total RNA, which contains subpopulations of actively translated mRNAs
      associated with polyribosomes (polysomes) and non-translated mRNAs that are not
      associated with polysomes. The goal of this study was to enhance previous gene
      expression analyses by identifying host mRNAs that become differentially
      associated with polysomes following pathogen inoculation. Total and polysomal RNA
      were extracted from barley (Hordeum vulgare) plants at 32 h after inoculation
      with Blumeria graminis f. sp. hordei, and Arabidopsis thaliana plants at 10 days
      after inoculation with Turnip mosaic virus. Gene expression profiles were
      obtained for each pathosystem, which represent diverse plant host-obligate
      pathogen interactions. Using this approach, host mRNAs were identified that were
      differentially associated with polysomes in response to pathogen treatment.
      Approximately 18% and 26% of mRNAs represented by probe sets on the Affymetrix
      Barley1 and Arabidopsis ATH1 GeneChips, respectively, differentially accumulated
      in the two populations in one or more combinations of treatment and genotype.
      Gene ontology analysis of mRNAs sharing the same pattern of accumulation in total
      and polysomal RNA identified gene sets that contained a significant number of
      functionally related annotations, suggesting both transcript accumulation and
      recruitment to polyribosomes are coordinately regulated in these systems.

PMID- 22660699
TI  - Raman spectroscopy as a potential tool for detection of Brucella spp. in milk.
AB  - Detection of Brucella, causing brucellosis, is very challenging, since the
      applied techniques are mostly time-demanding and not standardized. While the
      common detection system relies on the cultivation of the bacteria, further
      classical typing up to the biotype level is mostly based on phenotypic or
      genotypic characteristics. The results of genotyping do not always fit the
      existing taxonomy, and misidentifications between genetically closely related
      genera cannot be avoided. This situation gets even worse, when detection from
      complex matrices, such as milk, is necessary. For these reasons, the availability
      of a method that allows early and reliable identification of possible Brucella
      isolates for both clinical and epidemiological reasons would be extremely useful.
      We evaluated micro-Raman spectroscopy in combination with chemometric analysis to
      identify Brucella from agar plates and directly from milk: prior to these
      studies, the samples were inactivated via formaldehyde treatment to ensure a
      higher working safety. The single-cell Raman spectra of different Brucella,
      Escherichia, Ochrobactrum, Pseudomonas, and Yersinia spp. were measured to create
      two independent databases for detection in media and milk. Identification
      accuracies of 92% for Brucella from medium and 94% for Brucella from milk were
      obtained while analyzing the single-cell Raman spectra via support vector
      machine. Even the identification of the other genera yielded sufficient results,
      with accuracies of >90%. In summary, micro-Raman spectroscopy is a promising
      alternative for detecting Brucella. The measurements we performed at the single
      cell level thus allow fast identification within a few hours without a demanding
      process for sample preparation.

PMID- 22660700
TI  - The novel kasugamycin 2'-N-acetyltransferase gene aac(2')-IIa, carried by the
      IncP island, confers kasugamycin resistance to rice-pathogenic bacteria.
AB  - Kasugamycin (KSM), a unique aminoglycoside antibiotic, has been used in
      agriculture for many years to control not only rice blast caused by the fungus
      Magnaporthe grisea but also rice bacterial grain and seedling rot or rice
      bacterial brown stripe caused by Burkholderia glumae or Acidovorax avenae subsp.
      avenae, respectively. Since both bacterial pathogens are seed-borne and cause
      serious injury to rice seedlings, the emergence of KSM-resistant B. glumae and A.
      avenae isolates highlights the urgent need to understand the mechanism of
      resistance to KSM. Here, we identified a novel gene, aac(2')-IIa, encoding a KSM
      2'-N-acetyltransferase from both KSM-resistant pathogens but not from KSM
      sensitive bacteria. AAC(2')-IIa inactivates KSM, although it reveals no cross
      resistance to other aminoglycosides. The aac(2')-IIa gene from B. glumae strain
      5091 was identified within the IncP genomic island inserted into the bacterial
      chromosome, indicating the acquisition of this gene by horizontal gene transfer.
      Although excision activity of the IncP island and conjugational gene transfer was
      not detected under the conditions tested, circular intermediates containing the
      aac(2')-IIa gene were detected. These results indicate that the aac(2')-IIa gene
      had been integrated into the IncP island of a donor bacterial species. Molecular
      detection of the aac(2')-IIa gene could distinguish whether isolates are
      resistant or susceptible to KSM. This may contribute to the production of
      uninfected rice seeds and lead to the effective control of these pathogens by
      KSM.

PMID- 22660702
TI  - Biodiesel production by the green microalga Scenedesmus obliquus in a
      recirculatory aquaculture system.
AB  - Biodiesel production was examined with Scenedesmus obliquus in a recirculatory
      aquaculture system with fish pond discharge and poultry litter to couple with
      waste treatment. Lipid productivity of 14,400 liter ha(-1) year(-1) was projected
      with 11 cultivation cycles per year. The fuel properties of the biodiesel
      produced adhered to Indian and international standards.

PMID- 22660701
TI  - Development of a direct isolation procedure for free-living diazotrophs under
      controlled hypoxic conditions.
AB  - Free-living diazotrophs are diverse and ubiquitous in soil, contributing the
      nitrogen pool in natural ecosystems. The isolation of nitrogen-fixing
      microorganisms has relied on semisolid nitrogen-free medium enrichment, followed
      by multiple subculturing steps. These procedures limit the diversity of recovered
      isolates. In the current study, we investigated three different isolation
      strategies for free-living diazotrophs using a soil sample from the Amazon
      forest. The methods were (i) direct plating on solid nitrogen-free medium under a
      2% O(2) concentration, (ii) enrichment in semisolid nitrogen-free medium before
      plating on solid nitrogen-free medium under 2% O(2), and (iii) enrichment
      followed by subculturing in the semisolid nitrogen-free medium before plating on
      nitrogen containing medium under a 21% O(2) concentration. A total of 794
      isolates were differentiated by their genomic fingerprinting patterns, and
      strains with unique profiles were identified on the basis of sequencing of their
      16S rRNA gene. Isolates belonged to four bacterial phyla: Proteobacteria,
      Firmicutes, Actinobacteria, and Bacteriodetes. The novel strategy of combining a
      solid N-free medium and hypoxic conditions showed an increase of 62.6% in the
      diversity of diazotrophs in comparison to that obtained by the conventional
      semisolid medium-based methods. All isolates grew on the nitrogen-free medium
      under a 2% O(2) concentration, 78% of them showed the presence of the nifH gene,
      and 39% tested positive for acetylene reduction activity. Our results suggest
      that direct plating of soil dilutions on nitrogen-free solid medium under a 2%
      O(2) concentration is a useful strategy for the isolation of the diverse
      diazotrophic communities.

PMID- 22660703
TI  - Involvement of RpoN in regulating bacterial arsenite oxidation.
AB  - In this study with the model organism Agrobacterium tumefaciens, we used a
      combination of lacZ gene fusions, reverse transcriptase PCR (RT-PCR), and
      deletion and insertional inactivation mutations to show unambiguously that the
      alternative sigma factor RpoN participates in the regulation of As(III)
      oxidation. A deletion mutation that removed the RpoN binding site from the aioBA
      promoter and an aacC3 (gentamicin resistance) cassette insertional inactivation
      of the rpoN coding region eliminated aioBA expression and As(III) oxidation,
      although rpoN expression was not related to cell exposure to As(III). Putative
      RpoN binding sites were identified throughout the genome and, as examples,
      included promoters for aioB, phoB1, pstS1, dctA, glnA, glnB, and flgB that were
      examined by using qualitative RT-PCR and lacZ reporter fusions to assess the
      relative contribution of RpoN to their transcription. The expressions of aioB and
      dctA in the wild-type strain were considerably enhanced in cells exposed to
      As(III), and both genes were silent in the rpoN::aacC3 mutant regardless of
      As(III). The expression level of glnA was not influenced by As(III) but was
      reduced (but not silent) in the rpoN::aacC3 mutant and further reduced in the
      mutant under N starvation conditions. The rpoN::aacC3 mutation had no obvious
      effect on the expression of glnB, pstS1, phoB1, or flgB. These experiments
      provide definitive evidence to document the requirement of RpoN for As(III)
      oxidation but also illustrate that the presence of a consensus RpoN binding site
      does not necessarily link the associated gene with regulation by As(III) or by
      this sigma factor.

PMID- 22660704
TI  - Arcobacter in Lake Erie beach waters: an emerging gastrointestinal pathogen
      linked with human-associated fecal contamination.
AB  - The genus Arcobacter has been associated with human illness and fecal
      contamination by humans and animals. To better characterize the health risk posed
      by this emerging waterborne pathogen, we investigated the occurrence of
      Arcobacter spp. in Lake Erie beach waters. During the summer of 2010, water
      samples were collected 35 times from the Euclid, Villa Angela, and Headlands
      (East and West) beaches, located along Ohio's Lake Erie coast. After sample
      concentration, Arcobacter was quantified by real-time PCR targeting the
      Arcobacter 23S rRNA gene. Other fecal genetic markers (Bacteroides 16S rRNA gene
      [HuBac], Escherichia coli uidA gene, Enterococcus 23S rRNA gene, and tetracycline
      resistance genes) were also assessed. Arcobacter was detected frequently at all
      beaches, and both the occurrence and densities of Arcobacter spp. were higher at
      the Euclid and Villa Angela beaches (with higher levels of fecal contamination)
      than at the East and West Headlands beaches. The Arcobacter density in Lake Erie
      beach water was significantly correlated with the human-specific fecal marker
      HuBac according to Spearman's correlation analysis (r = 0.592; P < 0.001).
      Phylogenetic analysis demonstrated that most of the identified Arcobacter
      sequences were closely related to Arcobacter cryaerophilus, which is known to
      cause gastrointestinal diseases in humans. Since human-pathogenic Arcobacter spp.
      are linked to human-associated fecal sources, it is important to identify and
      manage the human-associated contamination sources for the prevention of
      Arcobacter-associated public health risks at Lake Erie beaches.

PMID- 22660706
TI  - Transovarial transmission of Rickettsia spp. and organ-specific infection of the
      whitefly Bemisia tabaci.
AB  - The whitefly Bemisia tabaci is a cosmopolitan insect pest that harbors Portiera
      aleyrodidarum, the primary obligatory symbiotic bacterium, and several
      facultative secondary symbionts. Secondary symbionts in B. tabaci are generally
      associated with the bacteriome, ensuring their vertical transmission; however,
      Rickettsia is an exception and occupies most of the body cavity, except the
      bacteriome. The mode of Rickettsia transfer between generations and its
      subcellular localization in insect organs have not been investigated. Using
      electron and fluorescence microscopy, we show that Rickettsia infects the
      digestive, salivary, and reproductive organs of the insect; however, it was not
      observed in the bacteriome. Rickettsia invades the oocytes during early
      developmental stages and resides in follicular cells and cytoplasm; it is mostly
      excluded when the egg matures; however, some bacterial cells remain in the egg,
      ensuring their transfer to subsequent generations. Rickettsia was localized to
      testicles and the spermatheca, suggesting a horizontal transfer between males and
      females during mating. The bacterium was further observed at large amounts in
      midgut cells, concentrating in vacuole-like structures, and was located in the
      hemolymph, specifically at exceptionally large amounts around bacteriocytes and
      in fat bodies. Organs further infected by Rickettsia included the primary
      salivary glands and stylets, sites of possible secretion of the bacterium outside
      the whitefly body. The close association between Rickettsia and the B. tabaci
      digestive system might be important for digestive purposes. The vertical
      transmission of Rickettsia to subsequent generations occurs via the oocyte and
      not, like other secondary symbionts, the bacteriome.

PMID- 22660705
TI  - Genotypic and chemotypic diversity of Neotyphodium endophytes in tall fescue from
      Greece.
AB  - Epichloid endophytes provide protection from a variety of biotic and abiotic
      stresses for cool-season grasses, including tall fescue. A collection of 85 tall
      fescue lines from 15 locations in Greece, including both Continental and
      Mediterranean germplasm, was screened for the presence of native endophytes. A
      total of 37 endophyte-infected lines from 10 locations were identified, and the
      endophytes were classified into five distinct groups (G1 to G5) based on physical
      characteristics such as colony morphology, growth rate, and conidial morphology.
      These classifications were supported by phylogenetic analyses of housekeeping
      genes tefA and tubB, and the endophytes were further categorized as Neotyphodium
      coenophialum isolates (G1, G4, and G5) or Neotyphodium sp. FaTG-2 (Festuca
      arundinacea taxonomic group 2 isolates (G2 and G3). Analyses of the tall fescue
      matK chloroplast genes indicated a population-wide, host-specific association
      between N. coenophialum and Continental tall fescue and between FaTG-2 and
      Mediterranean tall fescue that was also reflected by differences in colonization
      of host tillers by the native endophytes. Genotypic analyses of alkaloid gene
      loci combined with chemotypic (chemical phenotype) profiles provided insight into
      the genetic basis of chemotype diversity. Variation in alkaloid gene content,
      specifically the presence and absence of genes, and copy number of gene clusters
      explained the alkaloid diversity observed in the endophyte-infected tall fescue,
      with one exception. The results from this study provide insight into endophyte
      germplasm diversity present in living tall fescue populations.

PMID- 22660707
TI  - Forward genetic in planta screen for identification of plant-protective traits of
      Sphingomonas sp. strain Fr1 against Pseudomonas syringae DC3000.
AB  - Sphingomonas sp. strain Fr1 has recently been shown to protect Arabidopsis
      thaliana against the bacterial leaf pathogen Pseudomonas syringae DC3000. Here,
      we describe a forward genetic in planta screen to identify genes in Sphingomonas
      sp. Fr1 necessary for this effect. About 5,000 Sphingomonas sp. Fr1 mini-Tn5
      mutants were assayed for a defect in plant protection against a luxCDABE-tagged
      P. syringae DC3000 derivative in a space-saving 24-well plate system. The
      bioluminescence of the pathogen was used as the indicator of pathogen
      proliferation and allowed for the identification of Sphingomonas sp. Fr1 mutants
      that had lost the ability to restrict pathogen growth before disease symptoms
      were visible. Potential candidates were validated using the same miniaturized
      experimental system. Of these mutants, 10 were confirmed as plant protection
      defective yet colonization competent. The mutants were subsequently evaluated in
      a previously described standard microbox system, and plants showed enhanced
      disease phenotypes after pathogen infection relative to those inoculated with the
      parental strain as a control. However, the disease severities were lower than
      those observed for control plants that were grown axenically prior to pathogen
      challenge, which suggests that several traits may contribute to plant protection.
      Transposon insertion sites of validated mutants with defects in plant protection
      were determined and mapped to 7 distinct genomic regions. In conclusion, the
      established screening protocol allowed us to identify mutations that affect plant
      protection, and it opens the possibility to uncover traits important for in
      planta microbe-microbe interactions.

PMID- 22660708
TI  - Two genera of magnetococci with bean-like morphology from intertidal sediments of
      the Yellow Sea, China.
AB  - Magnetotactic bacteria have the unique capacity of being able to swim along
      geomagnetic field lines. They are Gram-negative bacteria with diverse
      morphologies and variable phylogenetic relatedness. Here, we describe a group of
      uncultivated marine magnetococci collected from intertidal sediments of Huiquan
      Bay in the Yellow Sea. They were coccoid-ovoid in morphology, with an average
      size of 2.8 +/- 0.3 MUm by 2.0 +/- 0.2 MUm. Differential interference contrast
      microscopy, fluorescence microscopy, and transmission electron microscopy
      revealed that each cell was apparently composed of two hemispheres. The cells
      synthesized iron oxide-type magnetosomes that clustered on one side of the cell
      at the interface between the two hemispheres. In some cells two chains of
      magnetosomes were observed across the interface. Each cell had two bundles of
      flagella enveloped in a sheath and displayed north-seeking helical motion. Two
      16S rRNA gene sequences having 91.8% identity were obtained, and their
      authenticity was confirmed by fluorescence in situ hybridization. Phylogenetic
      analysis revealed that the magnetococci are affiliated with the
      Alphaproteobacteria and are most closely related to two uncultured magnetococci
      with sequence identities of 92.7% and 92.4%, respectively. Because they display a
      >7% sequence divergence to all bacteria reported, the bean-like magnetococci may
      represent two novel genera.

PMID- 22660709
TI  - Actinobacterial nitrate reducers and proteobacterial denitrifiers are abundant in
      N2O-metabolizing palsa peat.
AB  - Palsa peats are characterized by elevated, circular frost heaves (peat soil on
      top of a permanently frozen ice lens) and are strong to moderate sources or even
      temporary sinks for the greenhouse gas nitrous oxide (N(2)O). Palsa peats are
      predicted to react sensitively to global warming. The acidic palsa peat
      Skalluvaara (approximate pH 4.4) is located in the discontinuous permafrost zone
      in northwestern Finnish Lapland. In situ N(2)O fluxes were spatially variable,
      ranging from 0.01 to -0.02 MUmol of N(2)O m(-2) h(-1). Fertilization with nitrate
      stimulated in situ N(2)O emissions and N(2)O production in anoxic microcosms
      without apparent delay. N(2)O was subsequently consumed in microcosms. Maximal
      reaction velocities (v(max)) of nitrate-dependent denitrification approximated 3
      and 1 nmol of N(2)O per h per gram (dry weight [g(DW)]) in soil from 0 to 20 cm
      and below 20 cm of depth, respectively. v(max) values of nitrite-dependent
      denitrification were 2- to 5-fold higher than the v(max) nitrate-dependent
      denitrification, and v(max) of N(2)O consumption was 1- to 6-fold higher than
      that of nitrite-dependent denitrification, highlighting a high N(2)O consumption
      potential. Up to 12 species-level operational taxonomic units (OTUs) of narG,
      nirK and nirS, and nosZ were retrieved. Detected OTUs suggested the presence of
      diverse uncultured soil denitrifiers and dissimilatory nitrate reducers, hitherto
      undetected species, as well as Actino-, Alpha-, and Betaproteobacteria. Copy
      numbers of nirS always outnumbered those of nirK by 2 orders of magnitude. Copy
      numbers of nirS tended to be higher, while copy numbers of narG and nosZ tended
      to be lower in 0- to 20-cm soil than in soil below 20 cm. The collective data
      suggest that (i) the source and sink functions of palsa peat soils for N(2)O are
      associated with denitrification, (ii) actinobacterial nitrate reducers and nirS
      type and nosZ-harboring proteobacterial denitrifiers are important players, and
      (iii) acidic soils like palsa peats represent reservoirs of diverse acid-tolerant
      denitrifiers associated with N(2)O fluxes.

PMID- 22660711
TI  - A synthetic arabinose-inducible promoter confers high levels of recombinant
      protein expression in hyperthermophilic archaeon Sulfolobus islandicus.
AB  - Despite major progresses in genetic studies of hyperthermophilic archaea,
      recombinant protein production in these organisms always suffers from low yields
      and a robust expression system is still in great demand. Here we report a
      versatile vector that confers high levels of protein expression in Sulfolobus
      islandicus, a hyperthermophilic crenarchaeon. Two expression vectors, pSeSD and
      pEXA, harboring 11 unique restriction sites were constructed. They contain coding
      sequences of two hexahistidine (6*His) peptide tags and those coding for two
      protease sites, the latter of which make it possible to remove the peptide tags
      from expressed recombinant proteins. While pEXA employed an araS promoter for
      protein expression, pSeSD utilized P(araS-SD), an araS derivative promoter
      carrying an engineered ribosome-binding site (RBS; a Shine-Dalgarno [SD]
      sequence). We found that P(araS-SD) directed high levels of target gene
      expression. More strikingly, N-terminal amino acid sequencing of recombinant
      proteins unraveled that the protein synthesized from pEXA-N-lacS lacked the
      designed 6*His tag and that translation initiation did not start at the ATG codon
      of the fusion gene. Instead, it started at multiple sites downstream of the 6*His
      codons. Intriguingly, inserting an RBS site upstream of the ATG codon regained
      the expression of the 6*His tag, as shown with pSeSD-N-lacS. These results have
      yielded novel insight into the archaeal translation mechanism. The crenarchaeon
      Sulfolobus can utilize N-terminal coding sequences of proteins to specify
      translation initiation in the absence of an RBS site.

PMID- 22660710
TI  - Association of Campylobacter jejuni metabolic traits with multilocus sequence
      types.
AB  - In this study, we describe the association of three Campylobacter jejuni
      metabolism-related traits, gamma-glutamyl-transpeptidase (GGT), fucose permease
      (fucP), and secreted L-asparaginase [ansB(s)], with multilocus sequence types
      (STs). A total of 710 C. jejuni isolates with known STs were selected and
      originated from humans, poultry, bovines, and the environment. Among these
      isolates, we found 31.1% to produce GGT and 49.3% and 30.3% to be positive for
      ansB(s) and fucP, respectively. The combination of GGT production, the presence
      of ansB(s), and the absence of fucP was associated with ST-22, ST-586, and the ST
      45 and ST-283 clonal complexes (CCs), which were the main STs and CCs found among
      the human and chicken isolates. The ST-21 CC was associated with the presence of
      fucP and was the major CC among the bovine isolates. Although the ST-61 CC was
      the second major CC among the bovine isolates, these isolates did not have any of
      the markers studied, making the role of fucP in bovine gut colonization
      questionable. The ST-45 CC was subdivided into three groups that were attributed
      solely to ST-45. One group showed a marker combination described previously,
      another group was found to be positive for ansB(s) only, and the third group did
      not have any of the markers studied. These results suggest that the host
      association of these markers seems to be indirect and may arise as a consequence
      of host-ST and -CC associations. Thus, a representative collection of STs should
      be tested to draw sensible conclusions in similar studies.

PMID- 22660712
TI  - Respiratory chain analysis of Zymomonas mobilis mutants producing high levels of
      ethanol.
AB  - We previously isolated respiratory-deficient mutant (RDM) strains of Zymomonas
      mobilis, which exhibited greater growth and enhanced ethanol production under
      aerobic conditions. These RDM strains also acquired thermotolerance.
      Morphologically, the cells of all RDM strains were shorter compared to the wild
      type strain. We investigated the respiratory chains of these RDM strains and
      found that some RDM strains lost NADH dehydrogenase activity, whereas others
      exhibited reduced cytochrome bd-type ubiquinol oxidase or ubiquinol peroxidase
      activities. Complementation experiments restored the wild-type phenotype. Some
      RDM strains seem to have certain mutations other than the corresponding
      respiratory chain components. RDM strains with deficient NADH dehydrogenase
      activity displayed the greatest amount of aerobic growth, enhanced ethanol
      production, and thermotolerance. Nucleotide sequence analysis revealed that all
      NADH dehydrogenase-deficient strains were mutated within the ndh gene, which
      includes insertion, deletion, or frameshift. These results suggested that the
      loss of NADH dehydrogenase activity permits the acquisition of higher aerobic
      growth, enhanced ethanol production, and thermotolerance in this industrially
      important strain.

PMID- 22660714
TI  - Pathogenic Escherichia coli found in sewage treatment plants and environmental
      waters.
AB  - We previously demonstrated that some Escherichia coli strains with uropathogenic
      properties survived treatment stages of sewage treatment plants (STPs),
      suggesting that they may be released into the environment. We investigated the
      presence of such strains in the surrounding environmental waters of four STPs
      from which these persistent strains were isolated. In all, 264 E. coli isolates
      were collected from 129 receiving water sites in a 20-km radius surrounding STPs.
      We also included 93 E. coli strains collected from 18 animal species for
      comparison. Isolates were typed using a high-resolution biochemical
      fingerprinting method (the PhPlate system), and grouped into common (C) types.
      One hundred forty-seven (56%) environmental isolates were identical to strains
      found in STPs' final effluents. Of these, 140 (95%) carried virulence genes (VGs)
      associated with intestinal pathogenic E. coli (IPEC) or uropathogenic E. coli
      (UPEC) and were found in a variety of sites within areas sampled. Of the
      remaining 117 environmental strains not identical to STP strains, 105 belonged to
      18 C types and 102 of them carried VGs found among IPEC or UPEC strains. These
      strains belonged mainly to phylogenetic groups A (A0 and A1) and B1 and to a
      lesser extent B2(2), B2(3), D1, and D2. Eight of 18 environmental C types,
      comprising 50 isolates, were also identical to bird strains. The presence of a
      high percentage of environmental E. coli in waters near STPs carrying VGs
      associated with IPEC and UPEC suggests that they may have derived from STP
      effluents and other nonpoint sources.

PMID- 22660715
TI  - Two gene clusters coordinate galactose and lactose metabolism in Streptococcus
      gordonii.
AB  - Streptococcus gordonii is an early colonizer of the human oral cavity and an
      abundant constituent of oral biofilms. Two tandemly arranged gene clusters,
      designated lac and gal, were identified in the S. gordonii DL1 genome, which
      encode genes of the tagatose pathway (lacABCD) and sugar phosphotransferase
      system (PTS) enzyme II permeases. Genes encoding a predicted phospho-beta
      galactosidase (LacG), a DeoR family transcriptional regulator (LacR), and a
      transcriptional antiterminator (LacT) were also present in the clusters. Growth
      and PTS assays supported that the permease designated EII(Lac) transports lactose
      and galactose, whereas EII(Gal) transports galactose. The expression of the gene
      for EII(Gal) was markedly upregulated in cells growing on galactose. Using
      promoter-cat fusions, a role for LacR in the regulation of the expressions of
      both gene clusters was demonstrated, and the gal cluster was also shown to be
      sensitive to repression by CcpA. The deletion of lacT caused an inability to grow
      on lactose, apparently because of its role in the regulation of the expression of
      the genes for EII(Lac), but had little effect on galactose utilization. S.
      gordonii maintained a selective advantage over Streptococcus mutans in a mixed
      species competition assay, associated with its possession of a high-affinity
      galactose PTS, although S. mutans could persist better at low pHs. Collectively,
      these results support the concept that the galactose and lactose systems of S.
      gordonii are subject to complex regulation and that a high-affinity galactose PTS
      may be advantageous when S. gordonii is competing against the caries pathogen S.
      mutans in oral biofilms.

PMID- 22660716
TI  - A specific mutation in the promoter region of the silent cel cluster accounts for
      the appearance of lactose-utilizing Lactococcus lactis MG1363.
AB  - The Lactococcus lactis laboratory strain MG1363 has been described to be unable
      to utilize lactose. However, in a rich medium supplemented with lactose as the
      sole carbon source, it starts to grow after prolonged incubation periods.
      Transcriptome analyses showed that L. lactis MG1363 Lac(+) cells expressed celB,
      encoding a putative cellobiose-specific phosphotransferase system (PTS) IIC
      component, which is normally silent in MG1363 Lac(-) cells. Nucleotide sequence
      analysis of the cel cluster of a Lac(+) isolate revealed a change from one of the
      guanines to adenine in the promoter region. We showed here that one particular
      mutation, taking place at increased frequency, accounts for the lactose-utilizing
      phenotype occurring in MG1363 cultures. The G-to-A transition creates a -10
      element at an optimal distance from the -35 element. Thus, a fully active
      promoter is created, allowing transcription of the otherwise cryptic cluster.
      Nuclear magnetic resonance (NMR) spectroscopy results show that MG1363 Lac(+)
      uses a novel pathway of lactose utilization.

PMID- 22660717
TI  - Involvement of two-component system CBO0366/CBO0365 in the cold shock response
      and growth of group I (proteolytic) Clostridium botulinum ATCC 3502 at low
      temperatures.
AB  - The role of the two-component system (TCS) CBO0366/CBO0365 in the cold shock
      response and growth of the mesophilic Clostridium botulinum ATCC 3502 at 15
      degrees C was demonstrated by induced expression of the TCS genes upon cold shock
      and impaired growth of the TCS mutants at 15 degrees C.

PMID- 22660718
TI  - Exploiting a natural auxotrophy for genetic selection.
AB  - We exploited the natural histidine auxotrophy of Francisella species to develop
      hisD (encodes histidinol dehydrogenase) as a positive selection marker. A shuttle
      plasmid (pBR103) carrying Escherichia coli hisD and designed for cloning of PCR
      fragments replicated in both attenuated and highly virulent Francisella strains.
      During this work, we formulated a simplified defined growth medium for
      Francisella novicida.

PMID- 22660713
TI  - Denaturing gradient gel electrophoresis and barcoded pyrosequencing reveal
      unprecedented archaeal diversity in mangrove sediment and rhizosphere samples.
AB  - Mangroves are complex ecosystems that regulate nutrient and sediment fluxes to
      the open sea. The importance of bacteria and fungi in regulating nutrient cycles
      has led to an interest in their diversity and composition in mangroves. However,
      very few studies have assessed Archaea in mangroves, and virtually nothing is
      known about whether mangrove rhizospheres affect archaeal diversity and
      composition. Here, we studied the diversity and composition of Archaea in
      mangrove bulk sediment and the rhizospheres of two mangrove trees, Rhizophora
      mangle and Laguncularia racemosa, using denaturing gradient gel electrophoresis
      (DGGE) and pyrosequencing of archaeal 16S rRNA genes with a nested-amplification
      approach. DGGE profiles revealed significant structural differences between bulk
      sediment and rhizosphere samples, suggesting that roots of both mangrove species
      influence the sediment archaeal community. Nearly all of the detected sequences
      obtained with pyrosequencing were identified as Archaea, but most were
      unclassified at the level of phylum or below. Archaeal richness was, furthermore,
      the highest in the L. racemosa rhizosphere, intermediate in bulk sediment, and
      the lowest in the R. mangle rhizosphere. This study shows that rhizosphere
      microhabitats of R. mangle and L. racemosa, common plants in subtropical
      mangroves located in Rio de Janeiro, Brazil, hosted distinct archaeal
      assemblages.

PMID- 22660719
TI  - Effects of sequential and simultaneous applications of bacteriophages on
      populations of Pseudomonas aeruginosa in vitro and in wax moth larvae.
AB  - Interest in using bacteriophages to treat bacterial infections (phage therapy) is
      growing, but there have been few experiments comparing the effects of different
      treatment strategies on both bacterial densities and resistance evolution. While
      it is established that multiphage therapy is typically more effective than the
      application of a single phage type, it is not clear if it is best to apply phages
      simultaneously or sequentially. We tried single- and multiphage therapy against
      Pseudomonas aeruginosa PAO1 in vitro, using different combinations of phages
      either simultaneously or sequentially. Across different phage combinations,
      simultaneous application was consistently equal or superior to sequential
      application in terms of reducing bacterial population density, and there was no
      difference (on average) in terms of minimizing resistance. Phage-resistant
      bacteria emerged in all experimental treatments and incurred significant fitness
      costs, expressed as reduced growth rate in the absence of phages. Finally, phage
      therapy increased the life span of wax moth larvae infected with P. aeruginosa,
      and a phage cocktail was the most effective short-term treatment. When the ratio
      of phages to bacteria was very high, phage cocktails cured otherwise lethal
      infections. These results suggest that while adding all available phages
      simultaneously tends to be the most successful short-term strategy, there are
      sequential strategies that are equally effective and potentially better over
      longer time scales.

PMID- 22660720
TI  - SLC2A2 mutations can cause neonatal diabetes, suggesting GLUT2 may have a role in
      human insulin secretion.
AB  - AIMS: The gene SLC2A2 encodes GLUT2, which is found predominantly in pancreas,
      liver, kidney and intestine. In mice, GLUT2 is the major glucose transporter into
      pancreatic beta cells, and biallelic Slc2a2 inactivation causes lethal neonatal
      diabetes. The role of GLUT2 in human beta cells is controversial, and biallelic
      SLC2A2 mutations cause Fanconi-Bickel syndrome (FBS), with diabetes rarely
      reported. We investigated the potential role of GLUT2 in the neonatal period by
      testing whether SLC2A2 mutations can present with neonatal diabetes before the
      clinical features of FBS appear. METHODS: We studied SLC2A2 in patients with
      transient neonatal diabetes mellitus (TNDM; n = 25) or permanent neonatal
      diabetes mellitus (PNDM; n = 79) in whom we had excluded the common genetic
      causes of neonatal diabetes, using a combined approach of sequencing and
      homozygosity mapping. RESULTS: Of 104 patients, five (5%) were found to have
      homozygous SLC2A2 mutations, including four novel mutations (S203R, M376R,
      c.963+1G>A, F114LfsX16). Four out of five patients with SLC2A2 mutations
      presented with isolated diabetes and later developed features of FBS. Four out of
      five patients had TNDM (16% of our TNDM cohort of unknown aetiology). One patient
      with PNDM remains on insulin at 28 months. CONCLUSIONS: SLC2A2 mutations are an
      autosomal recessive cause of neonatal diabetes that should be considered in
      consanguineous families or those with TNDM, after excluding common causes, even
      in the absence of features of FBS. The finding that patients with homozygous
      SLC2A2 mutations can have neonatal diabetes supports a role for GLUT2 in the
      human beta cell.

PMID- 22660730
TI  - Differential proteomic analysis of the response of Stenotrophomonas maltophilia
      to imipenem.
AB  - This study represents two different large-scale proteomic experiments analyzing
      the antibiotic response and the mechanisms of production of beta-lactamases in
      the nosocomial pathogen Stenotrophomonas maltophilia. Two-dimensional gel
      electrophoresis on the cytoplasmic protein fraction, together with iTRAQ(r)
      differential labeling and 2-D liquid chromatographic separation (2D-LC) MS/MS on
      the enriched membrane protein fraction, revealed 73 proteins with a change in
      abundance upon imipenem challenge. These proteins belong to several different
      functional pathways. We observe an increase in beta-lactamase production as well
      as in proteins important for their function in the periplasm. The up-regulation
      of the L1 and L2 beta-lactamases, along with their activator LysR transcriptional
      factor AmpR, is linked to an increase in proteins responsible for peptidoglycan
      remodeling and stress response. The interesting identification of an increase in
      abundance after treatment of the two-component GGDEF signaling protein and an
      integral membrane sensor signal transduction histidine kinase, indicates that
      induction of the beta-lactamases is not restricted to the ampR-ampD-ampG pathway.
      This is the first proteomic study in S. maltophilia upon imipenem stimulation to
      further unravel the cellular adaptation resulting in beta-lactamase production.

PMID- 22660735
TI  - Comparison of a homologous series of benzonaphthyridine anti-cancer agents in
      mice: divergence between tumour and plasma pharmacokinetics.
AB  - PURPOSE: N-[2-(dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6
      naphthyridine-4-carboxamide (SN 28049), a DNA-binding benzonaphthyridine, has
      shown curative activity against colon-38 adenocarcinoma after a single dose in
      mice. A homologous series of 5 compounds, where the 2-methyl group was replaced
      by a hydrogen, ethyl, propyl, or butyl, was used to evaluate the role of
      lipophilicity and tumour pharmacokinetics on their antitumour activity. METHODS:
      All analogues were administered (25 MUmol/kg) to healthy and tumour-bearing C57
      Bl/6 mice and concentrations were measured in plasma, brain, heart, kidney,
      liver, lung, and tumour tissues. Microsomal stability studies were performed with
      mouse livers and plasma protein binding studies by equilibrium dialysis. RESULTS:
      Plasma pharmacokinetics conformed to a model where increasing lipophilicity was
      associated with a decreasing area under the concentration-time curve (AUC), an
      increasing clearance and volume of distribution. In contrast, tumour
      pharmacokinetic parameters showed a very different relationship, where the AUC of
      the methyl derivative (2,334 MUM h) was 89-fold higher than that of the hydrogen
      derivative (26.3 MUM h), with other homologues having intermediate values. The
      tumour AUC correlated (r = -0.98, P = 2 * 10(-7)) with the in vivo antitumour
      activity of this series. The methyl derivative had a 22 min microsomal half-life,
      while other analogues ranged from 1.6 to 12.2 min. The plasma-free fraction
      decreased (17-5 %) significantly with lipophilicity (r = 0.96, P = 2 * 10(-7)).
      CONCLUSION: The plasma pharmacokinetics of this series is related to changes in
      drug lipophilicity. However, the tumour pharmacokinetics reveals a strong
      dependence on the nitrogen substituent on the benzonaphthyridine chromophore,
      with the methyl group providing by far the best tumour tissue retention.

PMID- 22660736
TI  - Intra-CSF administration of chemotherapy medications.
AB  - Leptomeningeal carcinomatosis is a devastating complication of cancer and is
      likely increasing in incidence. The combination of widespread neuro-axial spread
      based on CSF flow and the blood-brain barrier (BBB) has favored immediate local
      delivery of antineoplastic agents. With the BBB, the leptomeninges can be a
      sanctuary site to systemic cancers and goal of therapy includes preventing
      involvement in this space. Current therapies with U.S. Food and Drug
      Administration (FDA) approval are limited to treat hematologic cancers. Although
      lacking FDA guidance, a wider array of therapies is available to treat solid
      tumors. We provide an updated examination on both well-established intra-CSF
      chemotherapies as well as agents having limited data, but reports of therapeutic
      benefit.

PMID- 22660738
TI  - JOSPT perspectives for patients. Anterior knee pain: a holistic approach to
      treatment.
AB  - Pain under the kneecap, also known as anterior knee pain or patellofemoral pain,
      is one of the most common reasons why active people seek healthcare. Recently, a
      panel of 50 experts from 9 countries gathered in Belgium to discuss the potential
      causes of and best treatments for this condition. A synopsis of this meeting is
      published in the June 2012 issue of JOSPT and provides new insights and
      discussion of evidence-based treatments for those who have knee pain. J Orthop
      Sports Phys Ther 2012;42(6):573. doi:10.2519/jospt.2012.0505.

PMID- 22660737
TI  - Paclitaxel in combination with carboplatin as salvage treatment in patients with
      castration-resistant prostate cancer: a Hellenic oncology research group
      multicenter phase II study.
AB  - INTRODUCTION: To evaluate the efficacy and tolerance of biweekly paclitaxel and
      carboplatin combination in patients with castration-resistant prostate cancer.
      PATIENTS AND METHODS: Patients were treated with paclitaxel at the dose of 135
      mg/m(2) followed by carboplatin AUC 3 on day 1 every 2 weeks in cycles of 28
      days. RESULTS: Thirty-eight patients with castration-resistant prostate cancer
      were enrolled, and all of them had received frontline chemotherapy with docetaxel
      and prednisone, while 24 (63.2 %) had received 2 or more prior chemotherapy
      regimens. In an intention-to-treatment analysis, a clinical and/or biochemical
      response (>50 % decline) was observed in 10 patients (26.3 %; 95 % CI, 12.3-40.3
      %), stable disease in 13 (34.2 %) and progressive disease in 15 (39.5 %). The
      median duration of response was 6.1 months (range, 1.0-9.8), the median time to
      tumor progression (TTP) 3.6 months (95 % CI, 2.1-5.2) and the median overall
      survival 9.9 months (95 % CI, 6.2-13.6). The probability for 1-year survival was
      43 %. Grade 3 and 4 neutropenia was observed in three (7.9 %) and nine (23.7 %)
      patients, respectively. CONCLUSION: The biweekly administration of
      paclitaxel/carboplatin regimen in patients with castration-resistant prostate
      cancer is an active and well-tolerated regimen which merits to be further
      evaluated in the context of salvage treatment.

PMID- 22660739
TI  - Multiview light-sheet microscope for rapid in toto imaging.
AB  - We present a multiview selective-plane illumination microscope (MuVi-SPIM),
      comprising two detection and illumination objective lenses, that allows rapid in
      toto fluorescence imaging of biological specimens with subcellular resolution.
      The fixed geometrical arrangement of the imaging branches enables multiview data
      fusion in real time. The high speed of MuVi-SPIM allows faithful tracking of
      nuclei and cell shape changes, which we demonstrate through in toto imaging of
      the embryonic development of Drosophila melanogaster.

PMID- 22660740
TI  - Single-cell systems biology by super-resolution imaging and combinatorial
      labeling.
AB  - Fluorescence microscopy is a powerful quantitative tool for exploring regulatory
      networks in single cells. However, the number of molecular species that can be
      measured simultaneously is limited by the spectral overlap between fluorophores.
      Here we demonstrate a simple but general strategy to drastically increase the
      capacity for multiplex detection of molecules in single cells by using optical
      super-resolution microscopy (SRM) and combinatorial labeling. As a proof of
      principle, we labeled mRNAs with unique combinations of fluorophores using
      fluorescence in situ hybridization (FISH), and resolved the sequences and
      combinations of fluorophores with SRM. We measured mRNA levels of 32 genes
      simultaneously in single Saccharomyces cerevisiae cells. These experiments
      demonstrate that combinatorial labeling and super-resolution imaging of single
      cells is a natural approach to bring systems biology into single cells.

PMID- 22660741
TI  - Quantitative high-speed imaging of entire developing embryos with simultaneous
      multiview light-sheet microscopy.
AB  - Live imaging of large biological specimens is fundamentally limited by the short
      optical penetration depth of light microscopes. To maximize physical coverage, we
      developed the SiMView technology framework for high-speed in vivo imaging, which
      records multiple views of the specimen simultaneously. SiMView consists of a
      light-sheet microscope with four synchronized optical arms, real-time electronics
      for long-term sCMOS-based image acquisition at 175 million voxels per second, and
      computational modules for high-throughput image registration, segmentation,
      tracking and real-time management of the terabytes of multiview data recorded per
      specimen. We developed one-photon and multiphoton SiMView implementations and
      recorded cellular dynamics in entire Drosophila melanogaster embryos with 30-s
      temporal resolution throughout development. We furthermore performed high
      resolution long-term imaging of the developing nervous system and followed
      neuroblast cell lineages in vivo. SiMView data sets provide quantitative
      morphological information even for fast global processes and enable accurate
      automated cell tracking in the entire early embryo.

PMID- 22660767
TI  - Identification of a brevianamide F reverse prenyltransferase BrePT from
      Aspergillus versicolor with a broad substrate specificity towards tryptophan
      containing cyclic dipeptides.
AB  - A putative brevianamide F reverse prenyltransferase gene brePT was amplified from
      Aspergillus versicolor NRRL573 by using primers deduced from its orthologue notF
      in Aspergillus sp. MF297-2 and overexpressed in Escherichia coli. The soluble His
      tagged protein BrePT was purified to near homogeneity and assayed with tryptophan
      containing cyclic dipeptides in the presence of dimethylallyl diphosphate. BrePT
      showed much higher flexibility towards its aromatic substrates than NotF and
      accepted all of the 14 tested tryptophan-containing cyclic dipeptides. Structure
      elucidation of the enzyme products by NMR and MS analyses proved unequivocally
      the highly regiospecific reverse prenylation at C2 of the indole nucleus. K(M)
      values of BrePT were determined for its putative substrates brevianamide F and
      DMAPP at 32 and 98 MUM, respectively. Average turnover number (k (cat)) at 0.4 s
      1 was calculated from kinetic data of brevianamide F and DMAPP. K(M) values in
      the range of 0.082-2.9 mM and k (cat) values from 0.003 to 0.15 s-1 were
      determined for other 11 cyclic dipeptides. Similar to known fungal indole
      prenyltransferases, BrePT did not accept geranyl or farnesyl diphosphate as
      prenyl donor for its prenylation.

PMID- 22660768
TI  - A method for evaluating the host range of bacteriophages using phages
      fluorescently labeled with 5-ethynyl-2'-deoxyuridine (EdU).
AB  - The evaluation of bacteriophage (phage) host range is a significant issue in
      understanding phage and prokaryotic community interactions. However, in
      conventional methods, such as plaque assay, target host strains must be isolated,
      although almost all environmental prokaryotes are recalcitrant to cultivation.
      Here, we introduce a novel phage host range evaluation method using fluorescently
      labeled phages (the FLP method), which consists of the following four steps: (i)
      Fluorescently labeled phages are added to a microbial consortium, and host cells
      are infected and fluorescently labeled. (ii) Fluorescent cells are sorted by
      fluorescence-activated cell sorting. (iii) 16S rRNA gene sequences retrieved from
      sorted cells are analyzed, and specific oligonucleotide probes for fluorescence
      in situ hybridization (FISH) are designed. (iv) Cells labeled with both
      fluorescently labeled phage and FISH probe are identified as host cells. To
      verify the feasibility of this method, we used T4 phage and Escherichia coli as a
      model. We first used nucleic acid stain reagents for phage labeling; however, the
      reagents also stained non-host cells. Next, we employed the Click-iT EdU (5
      ethynyl-2'-deoxyuridine) assay kit from Invitrogen for phage labeling. Using EdU
      labeled T4 phage, we could specifically detect E. coli cells in a complex
      microbial consortium from municipal sewage. We also confirmed that FISH could be
      applied to the infected E. coli cells. These results suggest that this FLP method
      using the EdU assay kit is a useful method for evaluating phage host range and
      may have a potential application for various types of phages, even if their
      prokaryotic hosts are currently unculturable.

PMID- 22660769
TI  - Insight into microwave irradiation and enzyme catalysis in enantioselective
      resolution of DL-(+/-)-3-phenyllactic acid.
AB  - Lipase catalyzed kinetic resolution of DL-(+/-)-3-phenyllactic acid (DL-(+/-)-3
      PLA) was investigated to study the synergistic effect of microwave irradiation
      and enzyme catalysis. Lipases from different sources were employed for the
      transesterification of DL-(+/-)-3-PLA under otherwise similar conditions, among
      which Novozyme 435 efficiently catalyzed the resolution of DL-(+/-)-3-PLA to L-(
      )-O-acetyl-3-PLA using vinyl acetate as the acyl donor, showing excellent
      conversion (49%) and enantiomeric excess (>99%). The effect of various parameters
      affecting the initial rate, conversion and enantiomeric excess of the reaction
      were studied to establish kinetics and mechanism. There is a synergism between
      enzyme catalysis and microwave irradiation; an increase in initial rates up to
      1.8-fold was observed under microwave irradiation than that under conventional
      heating. The analysis of initial rate data showed that reaction obeys ternary
      complex (ordered bi-bi) mechanism with inhibition by DL-(+/-)-3-PLA. The
      calculated and simulated rates match very well showing the validity of the
      proposed kinetic model.

PMID- 22660770
TI  - Development of a short-term assay based on the evaluation of the plasma membrane
      integrity of the alga Pseudokirchneriella subcapitata.
AB  - Membrane integrity has been used as a criterion for the definition of cell
      viability. In the present work, staining conditions (time and dye concentration)
      for the evaluation of membrane integrity in a fluorescence microplate reader,
      using the membrane-impermeant nucleic-acid dye SYTOX Green, were optimized.
      Incubating Pseudokirchneriella subcapitata algal cells with 0.5 MUmol/l SYTOX
      Green for 40 min allowed a clear discrimination between live (intact plasma
      membrane) and dead cells (with compromised plasma membrane). Algal cell
      suspensions, labelled with SYTOX Green, exhibited a green fluorescence
      proportional to the fraction of the cells with a permeabilized plasma membrane.
      The optimized staining conditions were used to assess the toxicity of 1-pentanol
      on P. subcapitata in a short-term exposure (6 h) assay. The loss of membrane
      integrity in the cell population increased with the concentration of 1-pentanol.
      The 6-h EC(10) and EC(50) values were 7,617 mg/l 1-pentanol (95 % confidence
      limits 4,670-9,327) and 12,818 mg/l 1-pentanol (95 % confidence limits 10,929
      15,183), respectively. The developed microplate-based short-term assay can be
      useful in the high-throughput screening of toxics or environmental samples using
      the alga P. subcapitata.

PMID- 22660771
TI  - Cytotoxic metabolites from Perenniporia tephropora, an endophytic fungus from
      Taxus chinensis var. mairei.
AB  - Based on bioactivity-oriented isolation, the EtOAc extract of a culture broth of
      the endophytic fungus Perenniporia tephropora Z41 from Taxus chinensis var.
      mairei, with strong anti-Pyricularia oryzae activity, afforded a new
      sesquiterpenoid, perenniporin A (1), together with three known compounds,
      ergosterol (2), rel-(+)-(2aR,5R,5aR,8S,8aS,8bR)-decahydro-2,2,5,8-tetramethyl-2H
      naphtho[1,8-bc]genfuran-5-ol (3), and albicanol (4). Their structures were
      elucidated by means of spectroscopic methods. All the isolated compounds and the
      EtOAc extract of P. tephropora Z41 (EPT) were evaluated for their cytotoxic
      activity against three human cancer cell lines (HeLa, SMMC-7721, and PANC-1). EPT
      demonstrated significant cytotoxicity with IC(50) values ranging from 2 to 15
      MUg/mL. Compound 2 was the most cytotoxic constituent against the tested cell
      lines with IC(50) values of 1.16, 11.63, and 11.80 MUg/mL, respectively, while
      compounds 1, 3, and 4 exhibited moderate cytotoxicity with IC(50) values ranging
      from 6 to 58 MUg/mL. We conclude that the endophytic fungus P. tephropora is a
      promising source of novel and cytotoxic metabolites.

PMID- 22660772
TI  - Towards integrative annotation of the cell-type specific gene functional and
      signaling map in vascular endothelial cells.
AB  - Vascular endothelial cells (VECs), which form the inner surface of blood vessels,
      play essential roles in many physiological and pathological processes. VECs are
      exposed to various micro-environmental stimuli delivered by the circulatory
      systems. Systematically deciphering the gene functions and signaling circuits in
      VECs responsive to the complex micro-environmental stimuli is one of the
      fundamental tasks in vascular biology. Currently, several databases aim at genome
      widely annotating the gene functions and signaling circuits, but most of them
      take limited consideration on the cell-type specific information. And also,
      current annotations only provide the core genes involved in different signaling
      circuits, lacking the annotations on the peripheral signaling molecules or the
      signaling cross-talks. To quickly construct the genome-wide gene functional and
      signaling map in VECs, we developed a N[combining low line]etwork-based
      a[combining low line]n[combining low line]n[combining low line]o[combining low
      line]tating system (Nanno) by integrating cell-type specific gene expression
      profiles, genome-wide protein-protein interaction (PPI) networks, Gene Ontology
      (GO) annotations and microRNA (miRNA) target gene information. Using this system,
      we successfully re-annotated the genes involved in several essential cellular
      functions and also identified the signaling circuits under different stimuli in
      VECs in a cell-type specific manner. Many important genes, which are not included
      in GO annotations, can be recovered by Nanno. And several canonical signaling
      pathways and miRNAs are predicted to involve in the inflammatory and angiogenic
      signaling in VECs. The annotations suggest that there may exist cross-talks in
      cell cycle regulation between the two conditions.

PMID- 22660773
TI  - The impact of California's full-service partnership program on mental health
      related emergency department visits.
AB  - OBJECTIVE: This study examined the effects of California's 2005 Mental Health
      Services Act (MHSA) on the use of mental health-related emergency department
      visits. It focused on one MHSA program, the full-service partnership program, and
      hypothesized that individuals with public insurance who participate in the higher
      quality full-service partnership program would have fewer emergency department
      visits compared with clients with public insurance who receive usual care.
      METHODS: Data were obtained from the Short-Doyle/Medi-Cal (Medicaid) file, the
      Data Collection and Reporting system, and the Consumer and Service Information
      System, all maintained by the California Department of Mental Health. The
      analytic sample covered 931,218 observations (155,203 adults) ages 18 and older
      from January 2007 to June 2008. The data represented clients from seven counties,
      which made up 48.5% of the California population. Fixed-effects logistic
      regression was used and included a continuous measure of time, in quarters, in
      the full-service partnership program; separate quarter indicators; and quarter
      county interaction terms. The model thus controlled for both time-invariant
      personal characteristics (including personality as well as psychiatric and
      medical history as of entry into the study) and all time-varying county-level
      characteristics. RESULTS: Relative to persons receiving usual care, the odds of
      full-service partnership participants visiting the emergency department were 54%
      less after four quarters of treatment and 68% less after six quarters.
      CONCLUSIONS: The full-service partnership program was highly effective in
      reducing emergency visits. A statewide cost-effectiveness study should be
      conducted to determine the economic viability of the program.

PMID- 22660774
TI  - Mechanisms contributing to the dopamine induction of crawl-like bursting in leech
      motoneurons.
AB  - Dopamine (DA) activates fictive crawling behavior in the medicinal leech. To
      identify the cellular mechanisms underlying this activation at the level of crawl
      specific motoneuronal bursting, we targeted potential cAMP-dependent events that
      are often activated through DA(1)-like receptor signaling pathways. We found that
      isolated ganglia produced crawl-like motoneuron bursting after bath application
      of phosphodiesterase inhibitors (PDIs) that upregulated cAMP. This bursting
      persisted in salines in which calcium ions were replaced with equimolar cobalt or
      nickel, but was blocked by riluzole, an inhibitor of a persistent sodium current.
      PDI-induced bursting contained a number of patterned elements that were
      statistically similar to those observed during DA-induced fictive crawling,
      except that one motoneuron (CV) exhibited bursting during the contraction rather
      than the elongation phase of crawling. Although DA and the PDIs produced similar
      bursting profiles, intracellular recordings from motoneurons revealed differences
      in altered membrane properties. For example, DA lowered motoneuron excitability
      whereas the PDIs increased resting discharge rates. We suggest that PDIs (and DA)
      activate a sodium-influx-dependent timing mechanism capable of setting the crawl
      rhythm and that multiple DA receptor subtypes are involved in shaping and
      modulating the phase relationships and membrane properties of cell-specific
      members of the crawl network to generate crawling.

PMID- 22660775
TI  - Evoked-potential audiogram of an Indo-Pacific humpback dolphin (Sousa chinensis).
AB  - An evoked-potential audiogram was measured for an Indo-Pacific humpback dolphin
      (Sousa chinensis) living in the dolphinarium of Nanning Zoo, China. Rhythmic 20
      ms pip trains composed of cosine-enveloped 0.25 ms tone pips at a pip rate of 1
      kHz were presented as sound stimuli. The dolphin was trained to remain still at
      the water surface and to wear soft latex suction-cup EEG electrodes used to
      measure the animal's envelope-following evoked potentials to the sound stimuli.
      Responses to 1000 rhythmic 20 ms pip trains for each amplitude/frequency
      combination were averaged and analysed using a fast Fourier transform to obtain
      an evoked auditory response. The hearing threshold was defined as the zero
      crossing point of the response input-output function using linear regression.
      Fourteen frequencies ranging from 5.6 to 152 kHz were studied. The results showed
      that most of the thresholds were lower than 90 dB re. 1 MUPa (r.m.s.), covering a
      frequency range from 11.2 to 128 kHz, and the lowest threshold of 47 dB was
      measured at 45 kHz. The audiogram, which is a function of hearing threshold
      versus stimulus carrier frequency, presented a U-shape with a region of high
      hearing sensitivity (within 20 dB of the lowest threshold) between approximately
      20 and 120 kHz. At frequencies lower than this high-sensitivity region,
      thresholds increased at a rate of approximately 11 dB octave(-1) up to 93 dB at
      5.6 kHz. The thresholds at high frequencies above 108 kHz increased steeply at a
      rate of 130 dB octave(-1) up to 127 dB at 152 kHz.

PMID- 22660776
TI  - The neural mechanisms of antennal positioning in flying moths.
AB  - In diverse insects, the forward positioning of the antenna is often among the
      first behavioral indicators of the onset of flight. This behavior may be
      important for the proper acquisition of the mechanosensory and olfactory inputs
      by the antennae during flight. Here, we describe the neural mechanisms of
      antennal positioning in hawk moths from behavioral, neuroanatomical and
      neurophysiological perspectives. The behavioral experiments indicated that a set
      of sensory bristles called Bohm's bristles (or hair plates) mediate antennal
      positioning during flight. When these sensory structures were ablated from the
      basal segments of their antennae, moths were unable to bring their antennae into
      flight position, causing frequent collisions with the flapping wing. Fluorescent
      dye-fills of the underlying sensory and motor neurons revealed that the axonal
      arbors of the mechanosensory bristle neurons spatially overlapped with the
      dendritic arbors of the antennal motor neurons. Moreover, the latency between the
      activation of antennal muscles following stimulation of sensory bristles was also
      very short (<10 ms), indicating that the sensorimotor connections may be direct.
      Together, these data show that Bohm's bristles control antennal positioning in
      moths via a reflex mechanism. Because the sensory structures and motor
      organization are conserved across most Neoptera, the mechanisms underlying
      antennal positioning, as described here, are likely to be conserved in these
      diverse insects.

PMID- 22660777
TI  - Differential physiological responses of the German cockroach to social
      interactions during the ovarian cycle.
AB  - In many animal species, social interactions can influence the morphology,
      physiology and behavior of individuals, including their rate of development and
      reproduction. Reproduction in cockroaches is regulated by juvenile hormone III
      (JH), and social interactions have been shown to accelerate female reproduction
      in the German cockroach, Blattella germanica (L.), by stimulating JH production.
      However, it is not clear in this or any other insect species whether social
      facilitation of the reproductive rate occurs throughout the ovarian cycle or only
      at certain stages. We compared the effects of social interactions during the pre
      oviposition period (when JH production is high) and during gestation (when little
      JH is produced), as well as during the first ovarian cycle (when females are
      virgin) and the second ovarian cycle (after females had mated). Social
      interaction with one conspecific female was sufficient to accelerate JH
      production and oocyte maturation, but this effect was reversed by crowding.
      Social interactions also accelerated the onset of sexual receptivity in virgin
      females. However, social interactions failed to shorten gestation, suggesting
      that social cues stimulate JH production only when the corpora allata (CA) are
      active and not when CA activity is suppressed by the central nervous system.
      Females were most responsive to transient social isolation and transient social
      interactions when 2-3 days old, suggesting that they are particularly sensitive
      to social interactions when their CA become active. Overall, these results show
      that all JH-dependent events in the reproductive cycle of B. germanica females
      are under the strong influence of social interactions.

PMID- 22660778
TI  - Shape and material characteristics of the trachea in the leatherback sea turtle
      promote progressive collapse and reinflation during dives.
AB  - The leatherback turtle regularly undertakes deep dives and has been recorded
      attaining depths in excess of 1200 m. Its trachea is an almost solid, elliptical
      section tube of uncalcified hyaline cartilage with minimal connective tissue
      between successive rings. The structure appears to be advantageous for diving and
      perfectly designed for withstanding repeated collapse and reinflation. This study
      applies Boyle's law to the respiratory system (lungs, trachea and larynx) and
      estimates the changes in tracheal volume during a dive. These changes are
      subsequently compared with the results predicted by a corresponding finite
      element (FE) structural model, itself based on laboratory studies of the trachea
      of an adult turtle. Boyle's law predicts that the lungs will collapse first
      during the initial stages of a dive with tracheal compression beginning at much
      deeper depths after complete air mass expulsion from the lungs. The FE model
      reproduces the changes extremely well (agreeing closely with Boyle's law
      estimations) and provides visual representation of the deformed tracheal luminal
      area. Initially, the trachea compresses both ventrally and dorsally before
      levelling ventrally. Bulges are subsequently formed laterally and become more
      pronounced at deeper depths. The geometric configuration of the tracheal
      structure confers both homogeneity and strength upon it, which makes it extremely
      well suited for enduring repeated collapse and re-expansion. The structure
      actually promotes collapse and is an adaptation to the turtle's natural
      environment in which large numbers of deep dives are performed annually.

PMID- 22660779
TI  - Mitochondrial dynamics underlying thermal plasticity of cuttlefish (Sepia
      officinalis) hearts.
AB  - In the eurythermal cuttlefish Sepia officinalis, performance depends on hearts
      that ensure systemic oxygen supply over a broad range of temperatures. We
      therefore aimed to identify adjustments in energetic cardiac capacity and
      underlying mitochondrial function supporting thermal acclimation and adaptation
      that could be crucial for the cuttlefish's competitive success in variable
      environments. Two genetically distinct cuttlefish populations were acclimated to
      11, 16 and 21 degrees C. Subsequently, skinned and permeabilised heart fibres
      were used to assess mitochondrial functioning by means of high-resolution
      respirometry and a substrate-inhibitor protocol, followed by measurements of
      cardiac citrate synthase and cytosolic enzyme activities. Temperate English
      Channel cuttlefish had lower mitochondrial capacities but larger hearts than
      subtropical Adriatic cuttlefish. Warm acclimation to 21 degrees C decreased
      mitochondrial complex I activity in Adriatic cuttlefish and increased complex IV
      activity in English Channel cuttlefish. However, compensation of mitochondrial
      capacities did not occur during cold acclimation to 11 degrees C. In systemic
      hearts, the thermal sensitivity of mitochondrial substrate oxidation was high for
      proline and pyruvate but low for succinate. Oxygen efficiency of catabolism rose
      as temperature changed from 11 to 21 degrees C via shifts to oxygen-conserving
      oxidation of proline and pyruvate and via reduced relative proton leak. The
      changes observed for substrate oxidation, mitochondrial complexes, relative
      proton leak and heart mass improve energetic efficiency and essentially seem to
      extend tolerance to high temperatures and reduce associated tissue hypoxia. We
      conclude that cuttlefish sustain cardiac performance and, thus, systemic oxygen
      delivery over short- and long-term changes of temperature and environmental
      conditions by multiple adjustments in cellular and mitochondrial energetics.

PMID- 22660780
TI  - 3D reconstruction and analysis of wing deformation in free-flying dragonflies.
AB  - Insect wings demonstrate elaborate three-dimensional deformations and kinematics.
      These deformations are key to understanding many aspects of insect flight
      including aerodynamics, structural dynamics and control. In this paper, we
      propose a template-based subdivision surface reconstruction method that is
      capable of reconstructing the wing deformations and kinematics of free-flying
      insects based on the output of a high-speed camera system. The reconstruction
      method makes no rigid wing assumptions and allows for an arbitrary arrangement of
      marker points on the interior and edges of each wing. The resulting wing surfaces
      are projected back into image space and compared with expert segmentations to
      validate reconstruction accuracy. A least squares plane is then proposed as a
      universal reference to aid in making repeatable measurements of the reconstructed
      wing deformations. Using an Eastern pondhawk (Erythimus simplicicollis) dragonfly
      for demonstration, we quantify and visualize the wing twist and camber in both
      the chord-wise and span-wise directions, and discuss the implications of the
      results. In particular, a detailed analysis of the subtle deformation in the
      dragonfly's right hindwing suggests that the muscles near the wing root could be
      used to induce chord-wise camber in the portion of the wing nearest the
      specimen's body. We conclude by proposing a novel technique for modeling wing
      corrugation in the reconstructed flapping wings. In this method, displacement
      mapping is used to combine wing surface details measured from static wings with
      the reconstructed flapping wings, while not requiring any additional information
      be tracked in the high speed camera output.

PMID- 22660781
TI  - Glucosensing capacity in rainbow trout liver displays day-night variations
      possibly related to melatonin action.
AB  - To assess whether the glucosensing capacity in peripheral (liver and Brockmann
      bodies) and central (hypothalamus and hindbrain) locations of rainbow trout
      displays day-night variations in its response to changes in circulating glucose
      levels, we evaluated the response of parameters related to glucosensing [glucose,
      glycogen and glucose 6-phosphate levels, activities of glucokinase (GK), glycogen
      synthetase (GSase) and pyruvate kinase (PK), and mRNA abundance of GK, glucose
      transporter 2 (GLUT2), and K(ATP) channel subunits Kir6.x-like and sulfonylurea
      receptor (SUR)-like] in fish subjected to hyperglycemic treatment under night or
      day conditions. No day-night significant variations were noticed in the
      glucosensing capacity of the hypothalamus, hindbrain and Brockmann bodies. In
      contrast, a clear differential response was noticed in the liver, where glucose
      levels, GK activity (and mRNA levels) and GSase activity displayed increased
      values during the day in hyperglycemic fish compared with controls, and lower (GK
      mRNA levels) or non-existent (glucose, GK and GSase activities, and Kir6.x-like
      mRNA levels) values during the night. A similar decrease in parameters related to
      glucosensing in the liver was observed when fish under day conditions were
      treated with melatonin, suggesting a modulatory role of melatonin in day-night
      changes of the glucosensing response in the same tissue.

PMID- 22660783
TI  - Seasonal variation in energy expenditure is not related to activity level or
      water temperature in a large diving bird.
AB  - There is considerable interest in understanding how the energy budget of an
      endotherm is modulated from a physiological and ecological point of view. In this
      paper, we used daily (24 h) heart rate (f(H24)), as a proxy of daily energy
      expenditure (DEE) across seasons, to test the effect of locomotion activity and
      water temperature on the energy budget of a large diving bird. f(H24) was
      monitored continuously in common eiders (Somateria mollissima) during 7 months
      together with measures of time spent flying and time spent feeding. f(H24) varied
      substantially during the recording period, with numerous increases and decreases
      that occurred across seasons, although we did not find any relationship between
      f(H24) and the time spent active (feeding and flying). However, inactive heart
      rate (f(H,inactive)) decreased as locomotion activity increased, suggesting that
      common eiders were using some form of compensation when under a high work load.
      We were also unable to detect a negative relationship between water temperature
      and resting heart rate, a proxy of resting metabolic rate. This was unexpected,
      based on the assumption that high thermoregulation costs would be associated with
      cold waters. We showed instead that a high level of energy expenditure coincided
      with feather moult and warm waters, which suggests that the observed variable
      pattern of seasonal DEE was driven by these two factors. Nevertheless, our
      results indicate that compensation and possibly the timing of moult may be used
      as mechanisms to reduce seasonal variation in energy expenditure.

PMID- 22660782
TI  - Ammonia excretion in the freshwater planarian Schmidtea mediterranea.
AB  - In aquatic invertebrates, metabolic nitrogenous waste is excreted predominately
      as ammonia. Very little is known, however, of the underlying mechanisms of
      ammonia excretion, particularly in freshwater species. Our results indicate that
      in the non-parasitic freshwater planarian Schmidtea mediterranea, ammonia
      excretion depends on acidification of the apical unstirred layer of the body
      surface and consequent ammonia trapping. Buffering of the environment to a pH of
      7 or higher decreased the excretion rate. Inhibitor experiments suggested further
      that the excretion mechanism involves the participation of the V-type H(+)-ATPase
      and carbonic anhydrase and possibly also the Na(+)/K(+)-ATPase and Na(+)/H(+)
      exchangers. Alkalinization (pH 8.5, 2 days) of the environment led to a 1.9-fold
      increase in body ammonia levels and to a downregulation of V-ATPase (subunit A)
      and Rh-protein mRNA. Further, a 2 day exposure to non-lethal ammonia
      concentrations (1 mmol l(-1)) caused a doubling of body ammonia levels and led to
      an increase in Rh-protein and Na(+)/K(+)-ATPase (alpha-subunit) mRNA expression
      levels. In situ hybridization studies indicated a strong mRNA expression of the
      Rh-protein in the epidermal epithelium. The ammonia excretion mechanism proposed
      for S. mediterranea reveals striking similarities to the current model suggested
      to function in the gills of freshwater fish.

PMID- 22660784
TI  - The high aerobic capacity of a small, marsupial rat-kangaroo (Bettongia
      penicillata) is matched by the mitochondrial and capillary morphology of its
      skeletal muscles.
AB  - We examined the structure-function relationships that underlie the aerobic
      capacities of marsupial mammals that hop. Marsupials have relatively low basal
      metabolic rates (BMR) and historically were seen as 'low energy' mammals.
      However, the red kangaroo, Macropus rufus (family Macropodidae), has aerobic
      capacities equivalent to athletic placentals. It has an extreme aerobic scope
      (fAS) and its large locomotor muscles feature high mitochondrial and capillary
      volumes. M. rufus belongs to a modern group of kangaroos and its high fAS is not
      general for marsupials. However, other hopping marsupials may have elevated
      aerobic capacities. Bettongia penicillata, a rat-kangaroo (family Potoroidae), is
      a small (1 kg), active hopper whose fAS is somewhat elevated. We examined the
      oxygen delivery system in its muscles to ascertain links with hopping. An
      elevated fAS of 23 provided a relatively high maximal aerobic oxygen consumption
      ( ) in B. penicillata; associated with this is a skeletal muscle mass of 44% of
      body mass. Ten muscles were sampled to estimate the total mitochondrial and
      capillary volume of the locomotor muscles. Values in B. penicillata were similar
      to those in M. rufus and in athletic placentals. This small hopper had high
      muscle mitochondrial volume densities (7.1-11.9%) and both a large total
      capillary volume (6 ml kg(-1) body mass) and total capillary erythrocyte volume
      (3.2 ml kg(-1)). Apparently, a considerable aerobic capacity is required to
      achieve the benefits of the extended stride in fast hopping. Of note, the ratio
      of   to total muscle mitochondrial volume in B. penicillata was 4.9 ml O(2) min(
      1) ml(-1). Similar values occur in M. rufus and also placental mammals generally,
      not only athletic species. If such relationships occur in other marsupials, a
      fundamental structure-function relationship for oxygen delivery to muscles likely
      originated with or before the earliest mammals.

PMID- 22660785
TI  - Effect of dietary restriction on metabolic, anatomic and molecular traits in mice
      depends on the initial level of basal metabolic rate.
AB  - Dietary restriction (DR)-related delay of ageing is hypothesized to be mediated
      by the reduction of the metabolic rate (MR). However, studies on the effect of DR
      on MR have produced equivocal results. We demonstrated that this lack of
      congruency can be due to a variation in the initial level of MR within a given
      pool of experimental subjects. We subjected laboratory mice from two line types
      divergently selected for basal MR (BMR) to 30% DR lasting 6 months to test
      whether the effect of DR depends on the initial variation in BMR and peak MR. BMR
      and peak MR were independently affected by DR. The effect of DR was stronger in
      line types with higher initial levels of MR. Line-type-specific changes in the
      proportions of body components explained contrasting effects of DR on the mass
      corrected BMR, which decreased in the high-BMR line type and did not change in
      the low-BMR line type. We conclude that the initial variation in MR can
      significantly affect response to DR. However, we found no association between the
      level of MR and mechanisms underlying the susceptibility to or protection against
      oxidative stress.

PMID- 22660786
TI  - Effects of temperature and cadmium exposure on the mitochondria of oysters
      (Crassostrea virginica) exposed to hypoxia and subsequent reoxygenation.
AB  - Intertidal bivalves are commonly exposed to multiple stressors including periodic
      hypoxia, temperature fluctuations and pollution, which can strongly affect energy
      metabolism. We used top-down control and elasticity analyses to determine the
      interactive effects of intermittent hypoxia, cadmium (Cd) exposure and acute
      temperature stress on mitochondria of the eastern oyster Crassostrea virginica.
      Oysters were acclimated at 20 degrees C for 30 days in the absence or presence of
      50 MUg l(-1) Cd and then subjected to a long-term hypoxia (6 days at <0.5% O(2)
      in seawater) followed by normoxic recovery. Mitochondrial function was assessed
      at the acclimation temperature (20 degrees C), or at elevated temperature (30
      degrees C) mimicking acute temperature stress in the intertidal zone. In the
      absence of Cd or temperature stress, mitochondria of oysters showed high
      resilience to transient hypoxia. In control oysters at 20 degrees C,
      hypoxia/reoxygenation induced elevated flux capacity of all three studied
      mitochondrial subsystems (substrate oxidation, phosphorylation and proton leak)
      and resulted in a mild depolarization of resting mitochondria. Elevated proton
      conductance and enhanced capacity of phosphorylation and substrate oxidation
      subsystems may confer resistance to hypoxia/reoxygenation stress in oyster
      mitochondria by alleviating production of reactive oxygen species and maintaining
      high aerobic capacity and ATP synthesis rates during recovery. Exposure to
      environmental stressors such as Cd and elevated temperatures abolished the
      putative adaptive responses of the substrate oxidation and phosphorylation
      subsystems, and strongly enhanced proton leak in mitochondria of oysters
      subjected to hypoxia/reoxygenation stress. Our findings suggest that Cd exposure
      and acute temperature stress may lead to the loss of mitochondrial resistance to
      hypoxia and reoxygenation and thus potentially affect the ability of oysters to
      survive periodic oxygen deprivation in coastal and estuarine habitats.

PMID- 22660787
TI  - Trade-offs between burst performance and maximal exertion capacity in a wild
      amphibian, Xenopus tropicalis.
AB  - Trade-offs are thought to impose barriers to phenotypic diversification and may
      limit the evolutionary responses of organisms to environmental changes. In
      particular, locomotor trade-offs between endurance or maximal exertion capacity
      and burst performance capacity have been observed in some species and may
      constrain the ability of organisms to disperse. Here, we tested for the presence
      of locomotor trade-offs between maximal exertion and burst performance capacity
      in an aquatic frog, the tropical clawed frog (Xenopus tropicalis). Given the
      importance of overland dispersal for this species, we focused on terrestrial
      exertion capacity (time and distance jumped until exhaustion) and tested whether
      it trades-off with aquatic burst performance capacity (maximum instantaneous
      velocity and acceleration), which is likely to be relevant in the context of
      predator escape and prey capture. Our data show that in both sexes, individuals
      with longer hindlimbs display higher endurance. Additionally, in females forelimb
      length was positively correlated with aquatic burst performance capacity and
      negatively correlated with terrestrial exertion. Trade-offs between endurance and
      burst performance capacity were detected, but were significant in males only.
      Finally, males and females differ in morphology and performance. Our data suggest
      that trade-offs are not universal and may be driven by sex-dependent selection on
      locomotor capacity. Moreover, our results suggest that locomotor trade-offs may
      result in sex-biased dispersal under selection for improved endurance capacity as
      is expected under habitat fragmentation scenarios.

PMID- 22660788
TI  - Non-invasive lipid measurement in living insects using NMR microscopy.
AB  - Nuclear magnetic resonance (NMR) microscopy allows us to image and quantify the
      distribution of NMR-active nuclei in living specimens. Using high-field NMR
      microscopy at a magnetic field strength of 14.1 T and strong gradients up to 3 T
      m(-1), we show that separation of fat and water nuclear resonances in living
      insects can be achieved. In contrast to destructive conventional photometric and
      mass measurements, we demonstrate exemplarily in the European spruce bark beetle
      that NMR can be efficiently used to quantify absolute fat and water content in
      living insects. Additionally, anatomic images with a spatial in-plane resolution
      up to 10 MUm and with high soft tissue contrast were acquired. We demonstrate
      that fat distribution and fat consumption of living insects can be obtained by
      magnetic resonance imaging (MRI). This enables future research to address
      questions where single individuals have to be measured several times, which is
      not possible with conventional destructive methods.

PMID- 22660789
TI  - High genetic diversity and low differentiation in mud crab (Scylla paramamosain)
      along the southeastern coast of China revealed by microsatellite markers.
AB  - The mud crab (Scylla paramamosain) is a carnivorous portunid crab, mainly
      distributed along the southeastern coast of China. Mitochondrial DNA analysis in
      a previous study indicated a high level of genetic diversity and a low level of
      genetic differentiation. In this study, population genetic diversity and
      differentiation of S. paramamosain were investigated using nine microsatellite
      markers. In total, 397 wild specimens from 11 locations on the southeastern coast
      of China were sampled and genotyped. A high level of genetic diversity was
      observed, with the number of alleles, and the observed and expected
      heterozygosity per location in the range 7.8-9.6, 0.62-0.77 and 0.66-0.76,
      respectively. AMOVA analysis indicated a low level of genetic differentiation
      among the 11 locations, despite the fact that a statistically significant
      fixation index (F(ST)) value was found (F(ST)=0.0183, P<0.05). Out of 55 pairwise
      location comparisons, 39 showed significant F(ST) values (P<0.05), but all of
      them were lower than 0.05, except for one between Sanmen and Shantou locations.
      No significant deficiency of heterozygotes (inbreeding coefficient F(IS)=0.0007,
      P>0.05) was detected for all locations except Sanmen and Zhanjiang. Cluster
      analysis using UPGMA showed that all locations fell into one group except Sanmen.
      Significant association was found between genetic differentiation in terms of
      F(ST)/(1-F(ST)) and the natural logarithm of geographical distance (r(2)=0.1139,
      P=0.02), indicating that the genetic variation pattern closely resembled an
      isolation by distance model. This study supports the proposal of high genetic
      diversity and low genetic differentiation in S. paramamosain along the
      southeastern coast of China.

PMID- 22660795
TI  - Activating transcription factor 4 mediates hyperglycaemia-induced endothelial
      inflammation and retinal vascular leakage through activation of STAT3 in a mouse
      model of type 1 diabetes.
AB  - AIMS/HYPOTHESIS: There is convincing evidence that endoplasmic reticulum (ER)
      stress is implicated in the pathogenesis of diabetes and its complications;
      however, the mechanisms are not fully understood. This study aimed to dissect the
      role and signalling pathways of activating transcription factor 4 (ATF4) in ER
      stress-associated endothelial inflammation and diabetic retinopathy. METHODS: ER
      stress and ATF4 activity were manipulated by complementary pharmacological and
      genetic approaches in cultured retinal endothelial (TR-iBRB) cells. Diabetes was
      induced by streptozotocin in heterozygous Atf4 knockout and wild-type mice. ER
      stress markers, inflammatory cytokines and adhesion molecules, activation of the
      signal transducer and activator of transcription 3 (STAT3) pathway, and retinal
      vascular permeability were measured. RESULTS: High-glucose treatment resulted in
      rapid induction of ER stress, activation of ATF4, and increased production of
      inflammatory factors in TR-iBRB cells. Suppressing ER stress or inhibiting ATF4
      activity markedly attenuated high-glucose-induced production of intercellular
      adhesion molecule 1, TNF-alpha and vascular endothelial growth factor.
      Conversely, enhancing ER stress or overexpressing Atf4 was sufficient to induce
      endothelial inflammation, which was, at least in part, through activation of the
      STAT3 pathway. Furthermore, knockdown of the Stat3 gene or inhibiting STAT3
      activity restored ER homeostasis in cells exposed to high glucose and prevented
      ATF4 activation, suggesting that STAT3 is required for high-glucose-induced ER
      stress. Finally, we showed that downregulation of Atf4 significantly ameliorated
      retinal inflammation, STAT3 activation and vascular leakage in a mouse model of
      type 1 diabetes. CONCLUSIONS/INTERPRETATION: Taken together, our data reveal a
      pivotal role of ER stress and the ATF4/STAT3 pathway in retinal endothelial
      inflammation in diabetic retinopathy.

PMID- 22660791
TI  - Intraepithelial lymphocytes in celiac disease immunopathology.
AB  - Celiac disease is a T cell-mediated immune disorder induced by dietary gluten
      that is characterized by the development of an inflammatory anti-gluten CD4 T
      cell response, anti-gluten antibodies, and autoantibodies against tissue
      transglutaminase 2 and the activation of intraepithelial lymphocytes (IELs)
      leading to the destruction of the intestinal epithelium. Intraepithelial
      lymphocytes represent a heterogeneous population of T cells composed mainly of
      cytotoxic CD8 T cells residing within the epithelial layer, whose main role is to
      maintain the integrity of the epithelium by eliminating infected cells and
      promoting epithelial repair. Dysregulated activation of IELs is a hallmark of CD
      and is critically involved in epithelial cell destruction and the subsequent
      development of villous atrophy. In this review, we compare and contrast the
      phenotype and function of human and mouse small intestinal IELs under
      physiological conditions. Furthermore, we discuss how conditions of epithelial
      distress associated with overexpression of IL-15 and non-classical MHC class I
      molecules induce cytotoxic IELs to become licensed killer cells that upregulate
      activating NKG2D and CD94/NKG2C natural killer receptors, acquiring lymphokine
      killer activity. Pathways leading to dysregulated IEL activation could eventually
      be targeted to prevent villous atrophy and treat patients who respond poorly to
      gluten-free diet.

PMID- 22660796
TI  - Revisiting the connection between intramyocellular lipids and insulin resistance:
      a long and winding road.
AB  - In the mid-1990s, researchers began to re-examine type 2 diabetes from a more
      'lipocentric' perspective; giving strong consideration to the idea that systemic
      lipid imbalances give rise to glucose dysregulation, rather than vice versa. At
      the forefront of this paradigm shift was a report by Krssak and colleagues
      (Diabetologia 1999; 42:113-116) showing that intramyocellular lipid content,
      measured via the (then) novel application of proton nuclear magnetic resonance
      spectroscopy, served as a robust indicator of muscle insulin sensitivity in
      healthy individuals. A subsequent wave of investigations produced compelling
      correlative evidence linking ectopic lipid deposition within skeletal myocytes to
      the development of obesity-associated insulin resistance. But this relationship
      has proven much more complex than originally imagined, and scientists today are
      still left wondering if and how the intramyocellular accumulation of lipid
      droplets has a direct bearing on insulin action. Originally viewed as a simple
      storage depot, the lipid droplet is now recognised as an essential and
      sophisticated organelle that actively participates in numerous cellular
      processes. This edition of 'Then and now' revisits the connection between
      intramuscular lipids and insulin resistance and looks to future research aimed at
      understanding the dynamic interplay between lipid droplet biology and metabolic
      health.

PMID- 22660797
TI  - The optimal carrier for BMP-2: a comparison of collagen versus fibrin matrix.
AB  - INTRODUCTION: The aim of our study was to investigate in vitro and in a new in
      vivo rat model for impaired bone healing whether a low dose BMP-2 preparation in
      fibrin would be equivalent or better than the combination of collagen and a high
      dose of BMP-2 which is currently in clinical use. MATERIALS AND METHODS: In a 14
      day period we compared the in vitro release kinetics of an absorbable collagen
      sponge (ACS) with 72 MUg rhBMP-2 in the BMPC group and fibrin matrix with 10 MUg
      rhBMP-2 in the BMPF group. In our in vivo experiment a critical sized osteotomy
      was performed in the rat femur, which was filled with a spacer, inhibiting bone
      formation for a period of 4 weeks. In a second operation this spacer was removed
      and the test item was applied into the defect. We compared the BMPF and BMPC
      groups with the ACS alone, FIBRIN alone and the EMPTY (4w/8w) control groups. 4
      and 8 weeks after the second operation, specimens were analysed by X-ray and MUCT
      imaging. Mechanically stable femurs were biomechanically evaluated. RESULTS:
      Cumulative BMP-2 release was five times higher in the BMPF group than in the BMPC
      group during the observation period. MUCT analysis revealed that both the extent
      of bone union and the bone volume were significantly higher in the group with a
      lower dose of BMP-2 in fibrin matrix than in the groups without BMP-2 treatment.
      However there was no statistically significant difference between the BMPF and
      BMPC groups. CONCLUSION: We conclude that fibrin matrix is an excellent carrier
      for BMP-2 and that it provides equivalent results with a sevenfold lower dose of
      BMP-2 compared with ACS.

PMID- 22660798
TI  - Relations of serum COMP to cardiovascular risk factors and endothelial function
      in patients with rheumatoid arthritis treated with methotrexate and TNF-alpha
      inhibitors.
AB  - OBJECTIVE: To examine whether serum level of cartilage oligomeric matrix protein
      (S-COMP) is related to methotrexate (MTX) or to MTX and tumor necrosis factor
      alpha (TNF-alpha) combination treatment for rheumatoid arthritis (RA); and to
      investigate whether S-COMP is related to cardiovascular risk factors including
      endothelial dysfunction and level of anticitrullinated protein antibodies (ACPA)
      in patients with RA. METHODS: Clinical and laboratory measures, including S-COMP
      and reactive hyperemic index (RHI), were examined in 55 consecutive patients with
      RA starting with either MTX (n = 34) or MTX and anti-TNF-alpha treatment (n = 21)
      at baseline, and after 6 weeks and 6 months. RESULTS: S-COMP was similar in the 2
      treatment regimens during followup. We found a positive relationship between S
      COMP at baseline and the use of disease-modifying antirheumatic drugs the last
      year preceding the study (p = 0.001), and a negative relation to current use of
      systemic glucocorticosteroids (p = 0.044). The nonsignificant change in S-COMP
      between baseline and the 6-month followup was positively and independently
      related to change in ACPA level (p = 0.009). There was no significant association
      between RHI and level of S-COMP at baseline. CONCLUSION: The cartilage turnover
      marker S-COMP did not change significantly after 6 months' treatment with MTX
      with or without a TNF-alpha inhibitor in patients with RA. The positive
      association between S-COMP and ACPA suggests that these factors might interact,
      and could both be contributors to an unknown link between inflammation and
      cartilage destruction in patients with RA. S-COMP was not related to endothelial
      function in patients with RA, or to other cardiovascular risk factors studied.
      Clinical Trials registration number NCT00902005.

PMID- 22660799
TI  - Use of the 28-joint count yields significantly higher concordance between
      different examiners than the 66/68-joint count.
AB  - OBJECTIVE: Joint counts are the key outcome measure in rheumatoid arthritis (RA).
      There is a great variability between different assessors of the same patient;
      this variability can be reduced by standardized training. The training effect is
      far less pronounced for the 66/68-joint count compared to the 28-joint count. We
      evaluated the reason for the higher interrater disagreement in the 66/68 compared
      to the 28-joint count. METHODS: Participants in joint examination seminars
      evaluated a patient with RA before and after training in the European League
      Against Rheumatism technique. Joints were rated positive or negative for
      tenderness and swelling. The number of positive joints and the variability
      between examiners before and after the training were compared. Concordance was
      calculated for every single joint using the Fleiss-Kappa test. RESULTS: In total,
      256 health professionals were instructed in the 66/68-joint count and 84 in the
      28-joint count. The disagreement between examiners was higher for swelling than
      for tenderness. After the training, there was a significant reduction of
      interrater variability, which was more pronounced in the 28 than in the 66/68
      joint count. Comparisons between joint counts revealed that the joints of the
      feet were more likely to be rated negative, yet interrater disagreement was still
      high. CONCLUSION: Standardization of joint examination significantly reduces
      variability between assessors. The better performance of the 28-joint count is
      due to the lower number of joints examined, especially the foot joints, which
      remain difficult to assess reliably even after training.

PMID- 22660800
TI  - Serum S100A8/A9, but not follistatin-like protein 1 and interleukin 18, may be a
      useful biomarker of disease activity in adult-onset Still's disease.
AB  - OBJECTIVE: S100A8/A9, follistatin-like protein 1, and interleukin 18 (IL-18) have
      been suggested as biomarkers of disease activity in patients with systemic
      juvenile idiopathic arthritis or adult-onset Still's disease (AOSD). We
      investigated the clinical significance of these factors in AOSD. METHODS: Blood
      samples were collected from 36 patients with AOSD, 40 patients with rheumatoid
      arthritis (RA), and 33 healthy controls. Of the patients with AOSD, followup
      samples were collected from 16 patients after resolution of disease activity.
      RESULTS: Serum levels of S100A8/A9 (11.77 +/- 8.84 MUg/ml) in AOSD patients were
      higher than those in RA patients (3.53 +/- 3.43 MUg/ml; p < 0.001) and controls
      (2.49 +/- 1.83 MUg/ml; p < 0.001). Follistatin-like protein 1 levels in AOSD were
      not different from those in RA and controls. IL-18 levels in AOSD (7560.3 +/-
      7577.6 pg/ml) were higher than those in RA (217.7 +/- 292.1 pg/ml; p < 0.001) and
      controls (139.2 +/- 86.2 pg/ml; p < 0.001). The sensitivity and specificity of IL
      18 for diagnosing AOSD was highest with a cutoff value of 366.1 pg/ml. Serum
      S100A8/A9 correlated with leukocyte count, erythrocyte sedimentation rate, C
      reactive protein, ferritin, and systemic disease score; however, IL-18 correlated
      only with ferritin and systemic disease score. S100A8/A9 was decreased after
      disease activity was resolved in followup of AOSD patients (9.96 +/- 7.35 MUg/ml
      in active AOSD vs 3.6 +/- 4.77 MUg/ml in resolved cases; p = 0.001). The change
      of S100A8/A9 was well correlated with that of systemic disease score. CONCLUSION:
      The data suggest that serum S100A8/A9 may be a useful biomarker for evaluating
      disease activity in patients with AOSD.

PMID- 22660802
TI  - Prediction of cardiovascular events in patients with ankylosing spondylitis and
      psoriatic arthritis: role of lipoproteins in a high-risk population.
AB  - OBJECTIVE: To evaluate lipids and apolipoproteins as predictors of cardiovascular
      mortality and morbidity (CVD) in patients with spondyloarthritis (SpA). METHODS:
      In the pooled cohort of participants in the IDEAL, TNT, and CARDS trials, 50 had
      ankylosing spondylitis (AS), 36 had psoriatic arthritis (PsA), and 21,641 did not
      have AS or PsA (non-SpA). We compared lipid levels at baseline between AS or PsA
      and non-SpA, and hazard ratios (HR) for CVD were calculated in a Cox proportional
      hazard model. RESULTS: Atherogenic lipids were lower in samples from AS, but not
      in PsA, compared to non-SpA. The HR for 1 SD increase in baseline lipids for
      future CVD was for total cholesterol 1.39 (95% CI 0.82, 2.36) in AS, 1.01 (95% CI
      0.44, 2.31) in PsA, and 1.10 (95% CI 1.07, 1.14) in non-SpA. Both high-density
      lipoprotein (HDL) and apolipoprotein (ApoA-1) were significantly associated with
      CVD in AS (HR 3.67, 95% CI 1.47, 9.06, and HR 1.89, 95% CI 1.02, 3.54,
      respectively), in contrast to PsA (HDL: HR 1.03, 95% CI 0.49, 2.15; ApoA-1: HR
      0.79, 95% CI 0.34, 1.89) and non-SpA (HDL: HR 0.86, 95% CI 0.84, 0.89; ApoA-1: HR
      0.88, 95% CI 0.85, 0.91). CONCLUSION: HDL and ApoA-1 were surprisingly associated
      with increased risk of future CVD in patients with AS, whereas these lipids were
      protective in non-SpA.

PMID- 22660801
TI  - A multidimensional model of fatigue in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate a multidimensional model testing disease activity, mood
      disturbance, and poor sleep quality as determinants of fatigue in patients with
      rheumatoid arthritis (RA). METHOD: The data of 106 participants were drawn from
      baseline of a randomized comparative efficacy trial of psychosocial interventions
      for RA. Sets of reliable and valid measures were used to represent model
      constructs. Structural equation modeling was used to test the direct effects of
      disease activity, mood disturbance, and poor sleep quality on fatigue, as well as
      the indirect effects of disease activity as mediated by mood disturbance and poor
      sleep quality. RESULTS: The final model fit the data well, and the specified
      predictors explained 62% of the variance in fatigue. Higher levels of disease
      activity, mood disturbance, and poor sleep quality had direct effects on fatigue.
      Disease activity was indirectly related to fatigue through its effects on mood
      disturbance, which in turn was related to poor sleep quality. Mood disturbance
      also indirectly influenced fatigue through poor sleep quality. CONCLUSION: Our
      findings confirmed the importance of a multidimensional framework in evaluating
      the contribution of disease activity, mood disturbance, and sleep quality to
      fatigue in RA using a structural equation approach. Mood disturbance and poor
      sleep quality played major roles in explaining fatigue along with patient
      reported disease activity.

PMID- 22660803
TI  - Persistent or new onset microscopic hematuria in patients with small vessel
      vasculitis in remission: findings on renal biopsy.
AB  - OBJECTIVE: Hematuria is considered a sign of active renal disease in patients
      with small-vessel vasculitis. In patients who are in apparent clinical remission,
      presence of persistent or new-onset microscopic hematuria may reflect active
      vasculitis, damage, or other glomerular pathology. METHODS: We identified 74
      patients from the Johns Hopkins Renal Pathology database between 1995 and 2009
      with the diagnosis of pauciimmune glomerulonephritis (GN). Among them we
      identified 9 who were in clinical remission and underwent a renal biopsy for
      evaluation of persistent or new-onset hematuria. RESULTS: Nine patients with
      small-vessel vasculitis, 8 antineutrophil cytoplasmic antibody (ANCA)-positive
      and 1 ANCA-negative, underwent a renal biopsy at variable time periods after
      remission of vasculitis (6 to 164 months) for persistent microscopic hematuria (n
      = 6) or new-onset microscopic hematuria (n = 3). All patients were in apparent
      clinical remission at the time of renal biopsy. Of the 3 patients presenting with
      new-onset hematuria, 2 had crescentic IgA nephropathy and 1 had healed crescentic
      pauciimmune GN. Of the 6 patients with persistent hematuria, 2 had
      arteriosclerosis, 2 had focal segmental glomerulosclerosis, and 2 had global and
      segmental glomerulosclerosis and healed crescentic GN, and none had active
      vasculitis. CONCLUSION: Microscopic hematuria in patients with renal vasculitis
      otherwise in remission could represent chronic glomerular injury from prior
      episode of vasculitis or may represent new glomerular pathology. Renal biopsy
      should be considered in these patients to guide therapy.

PMID- 22660804
TI  - Screening for cognitive impairment in systemic lupus erythematosus.
AB  - OBJECTIVE: We examined the association between responses on a screening
      questionnaire and objective performance on a computer-administered test of
      cognitive abilities in systemic lupus erythematosus (SLE). METHODS: The Cognitive
      Symptom Inventory (CSI) and Hospital Anxiety and Depression Scales (HADS)
      questionnaires were compared in patients with SLE or rheumatoid arthritis (RA).
      The Automated Neuropsychological Assessment Metrics (ANAM) was used to evaluate
      cognitive performance in patients with SLE. Efficiency of performance was
      measured by "throughput" (number of correct responses per minute) and "inverse
      efficiency" (response speed/proportion of correct responses). Linear regression
      was applied to log-transformed CSI scores to examine their associations with ANAM
      scores and other factors. RESULTS: Patients with SLE (n = 68) or RA (n = 33) were
      similar in age, sex, ethnicity, and education status (p > 0.05). Patients with
      SLE had higher total CSI scores (33.6 +/- 10.5 vs 29.4 +/- 6.8, respectively; p =
      0.041) and attention/concentration subscale CSI scores (15.7 +/- 5.3 vs 13.3 +/-
      3.4; p = 0.016) compared to patients with RA. In patients with SLE there was a
      positive association between CSI scores and neuropsychiatric (NP) events at the
      time of testing (p = 0.0006), HADS anxiety (p < 0.0001), and depression (p <
      0.0001) scores. After adjustment for age, education, disease duration, and NP
      events at the time of testing, there was no significant association (p > 0.05)
      between ANAM and CSI scores in patients with SLE. The results were similar using
      either "throughput" or "inverse efficiency" or the number of impaired ANAM
      subscales after adjustment for simple reaction time. CONCLUSION: The CSI self
      report questionnaire of cognitive symptoms does not reliably screen for
      efficiency of cognitive processing in patients with SLE. Rather, cognitive
      complaints reported in the CSI are influenced by the presence of anxiety and
      depression.

PMID- 22660805
TI  - Improved health-related quality of life and physical function in patients with
      refractory chronic gout following treatment with pegloticase: evidence from phase
      III randomized controlled trials.
AB  - OBJECTIVE: To assess the efficacy of pegloticase on pain, physical function, and
      health-related quality of life (HRQOL) in patients with refractory chronic gout.
      METHODS: Subjects in 2 replicate, 6-month, randomized controlled phase III trials
      received intravenous infusions of pegloticase 8 mg twice monthly (biweekly
      group), pegloticase alternating with placebo (8-mg monthly group), or placebo.
      Medical Outcomes Study Short Form-36 (SF-36), Health Assessment Questionnaire
      Disability Index (HAQ-DI), patient global assessment of disease activity (PtGA),
      and pain by visual analog scale were completed at weeks 1 (baseline), 13, 19, and
      25. Prespecified pooled analyses of patient-reported outcomes were performed by
      combining values for each treatment group (biweekly treatment, monthly treatment,
      and placebo) at Week 25. RESULTS: Of 212 patients enrolled, 157 (74.1%) completed
      treatment. At entry, mean age was 55.4 years (range 23-89 yrs) and mean plasma
      uric acid was 9.7 mg/dl; most were male (81.6%) and white (67.5%). Subjects
      reported an average of 9.8 flares in the previous 18 months. Baseline SF-36
      physical component summary (PCS) scores were > 1.5 SD below US normative values.
      At Week 25, mean changes from baseline in PtGA, pain, HAQ-DI, and PCS scores were
      statistically significant and exceeded minimum clinically important differences
      (MCID) in the biweekly treatment group, compared with little to no improvement in
      placebo group. Statistically significant improvements greater than or equal to
      MCID were reported in 6 of 8 SF-36 domains. Monthly pegloticase resulted in
      significantly improved PtGA, HAQ-DI, PCS, and 3 SF-36 domains. CONCLUSION:
      Pegloticase therapy resulted in statistically significant and clinically
      meaningful improvements in PtGA, pain, physical function, and HRQOL.

PMID- 22660806
TI  - Seasonal variation in the activity of systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether there is any seasonal variation in the activity
      of systemic lupus erythematosus (SLE) overall and by individual organs. METHODS:
      The study group comprised 2102 patients with SLE who were followed in a
      prospective longitudinal cohort study. In this cohort, 92.3% of the patients were
      women. The mean +/- SD age of the patients was 47.9 +/- 13.9 years, 56.3% were
      white, 37.1% were African American, and 3.1% were Asian. Global disease activity
      was recorded by the Safety of Estrogens in Lupus Erythematosus National
      Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)
      and the physician's global assessment. Activity of each organ was also recorded
      using SLEDAI terms and a visual analog scale (VAS; 0 to 3). RESULTS: There was
      significant seasonal variation in photosensitive rash (p < 0.0001), which was
      more frequent in the spring and summer months (p < 0.0001). There was
      significantly more arthritis activity in spring and summer, as measured by both
      SELENA-SLEDAI (p = 0.0057) and the joint VAS (p = 0.0047). A decrease in renal
      activity was found in the summer months compared to the rest of the year (p =
      0.0397). Serositis recorded by VAS had higher activity from August to October (p
      = 0.0392). Anti-dsDNA levels were significantly higher during October and
      November (p < 0.0001). There was significant seasonal variation in
      antiphospholipid antibody levels (p < 0.0001) and lupus anticoagulant (p =
      0.0003). We found a significant variation in activity through the year in global
      disease activity as measured by SELENA-SLEDAI (p = 0.048). CONCLUSION: In the
      Hopkins Lupus Cohort, skin and joint activity is increased during the spring and
      summer, but other organs have different patterns. These seasonal variations
      likely reflect environmental factors that influence disease activity, including
      ultraviolet light and infections.

PMID- 22660807
TI  - Patient-acceptable symptom state as an outcome measure in the daily care of
      patients with ankylosing spondylitis.
AB  - OBJECTIVE: We assessed the prevalence of patients with ankylosing spondylitis
      (AS), rating their state as acceptable (patient-acceptable symptom state; PASS),
      among 190 patients with AS seen in daily practice. Factors associated with PASS
      status and PASS thresholds for outcome measures were also analyzed. METHODS: The
      characteristics of patients with affirmative and negative assignment to PASS were
      compared. Associated factors were estimated by logistic regression models and
      PASS thresholds by the 75th percentile and receiver-operating characteristic
      curve methods. RESULTS: A total of 77% of patients rated their state as
      acceptable (95% CI 62-91). These patients were taking fewer nonsteroidal
      antiinflammatory drugs and corticosteroids, practiced more exercise, had less
      anxiety and depression, and had lower values of all patient-reported outcome
      measures, physicians' assessment, AS Disease Activity Score (ASDAS) and C
      reactive protein. Lower values of Bath AS Disease Activity Index and physician's
      global assessment were independent factors associated with acceptable symptom
      state. High rates of anxiety and depression were found in patients not in PASS.
      The thresholds with the 75th percentile approach were 4.55 for the BASDAI and
      2.84 for the ASDAS. Fifty-three percent of patients in PASS had a high or very
      high disease activity state according to ASDAS cutoff values. CONCLUSION: A high
      percentage of patients with AS in daily practice declared that their symptom
      state was acceptable. PASS status correlated with physician global assessment and
      BASDAI. PASS thresholds for common recommended outcome measures were relatively
      high and many patients in PASS had unacceptably high disease activity states
      according to ASDAS. Other factors such as psychological problems may influence a
      negative PASS state.

PMID- 22660808
TI  - Preventing friction-induced chondrocyte apoptosis: comparison of human synovial
      fluid and hylan G-F 20.
AB  - OBJECTIVE: Symptomatic osteoarthritis (OA) is a common painful disease with
      limited treatment options. A rising number of patients with OA have been treated
      with intraarticular injections of hyaluronic acid, including the high-molecular
      weight hylan G-F 20, which is injected following arthrocentesis. We investigated
      the effectiveness of hylan G-F 20 to lower coefficient of friction (COF) and
      prevent chondrocyte apoptosis in vitro. METHODS: A disc-on-disc bovine cartilage
      bearing was used to measure the static and kinetic COF when lubricated with hylan
      G-F 20, human synovial fluid (HSF), and phosphate buffered saline (PBS).
      Following friction testing, we stained paraffin-embedded sections of these
      cartilage bearings for activated caspase-3, a marker of apoptosis. RESULTS:
      Bearings lubricated with hylan G-F 20 had kinetic COF values that were similar to
      bearings lubricated with PBS, but significantly higher than those lubricated with
      HSF. There were no significant differences in static COF values in bearings
      lubricated with hylan G-F 20 as compared to PBS or HSF. However, bearings
      lubricated with HSF had significantly lower static COF values compared to
      bearings lubricated with PBS. The mean percentage of caspase-3-positive
      chondrocytes in the superficial and upper intermediate zones of bearings
      lubricated with hylan G-F 20 was significantly higher compared to that of
      bearings lubricated with HSF or unloaded controls, but significantly lower than
      in those lubricated with PBS. CONCLUSION: These findings indicate that joint
      lubrication may prevent chondrocyte apoptosis by lowering the COF. Further,
      removal of synovial fluid prior to hylan G-F 20 injection may be detrimental to
      cartilage health.

PMID- 22660809
TI  - Vascular leak is a central feature in the pathogenesis of systemic sclerosis.
AB  - OBJECTIVE: The main histopathological focus of systemic sclerosis (SSc) has
      concentrated on fibrotic changes. We investigated the microvasculature
      alterations in the skin of patients with SSc at various stages of disease
      duration with whole-field digital microscopy. METHODS: Twenty consecutive
      patients with SSc, 1 with Raynaud's phenomenon (RP) without SSc, and 4 healthy
      controls underwent punch biopsy on the medial forearm. Eighteen patients were
      included in the primary analysis. Two with recent-onset diffuse cutaneous
      disease, 1 repeat SSc biopsy, and 1 patient with RP without SSc were also
      evaluated. All specimens were processed with histochemical stains and
      immunohistochemistry. We analyzed microvasculature abnormalities in an objective
      and systematic manner taking advantage of recent advances in whole-field digital
      microscopy. This analysis was coupled with ultrastructural evaluation performed
      with transmission electron microscopy (TEM). RESULTS: Whole-field digital
      microscopy and TEM of SSc skin biopsies revealed that endothelial abnormalities
      are a universal feature regardless of clinical features and/or duration of
      disease. These features were not seen in any healthy control specimens or in the
      single RP patient samples. Whole-field digital microscopy identified increased
      interstitial edema (31.0% +/- 9.6% vs 17.6% +/- 3.3% in controls; p = 0.009) and
      fibrosis (75.6% +/- 5.7% vs 66.1% +/- 9.8% in controls; p = 0.02) in all patients
      with SSc. Lower CD34 staining was seen in SSc compared to healthy controls (0.32%
      +/- 0.22% vs 1.31% +/- 0.34%; p < 0.0001) and within the SSc population with
      interstitial lung disease (0.55% +/- 0.22% vs 0.15% +/- 0.16%; p = 0.01).
      Perivascular and interstitial infiltrate of mast cells was present in all SSc
      specimens. CONCLUSION: Whole-field digital microscopy offers a means of rapidly
      carrying out objective, fully quantitative, and reproducible measurements of
      microscopic features of SSc microvascular change. The universal morphologically
      abnormal endothelial cells and interstitial edema in all patients with SSc
      biopsied suggests that SSc may be intrinsically a disease of the endothelium
      characterized by vascular leak.

PMID- 22660811
TI  - Ten-year absolute fracture risk and hip bone strength in Canadian women with
      systemic lupus erythematosus.
AB  - OBJECTIVE: Women with systemic lupus erythematosus (SLE) are at risk of
      osteoporosis (OP) and fractures because of SLE or its treatments. We aimed to
      determine in women with SLE (1) the prevalence of low bone mass (LBM) in those <
      50 years of age and OP in those > 50 years of age; (2) the 10-year absolute
      fracture risk in those > 40 years of age using the Canadian Fracture Risk
      Assessment Tool (FRAX); (3) bone quality using hip structural analysis (HSA); and
      (4) the associations between HSA and age, SLE duration, and corticosteroid
      exposure. METHODS: Women without prior OP fractures were eligible. Bone mineral
      densities at the hip, spine, and femoral neck were determined using dual-energy x
      ray absorptiometry. OP was determined using World Health Organization definitions
      for participants aged >= 50 years (32.8%), and LBM was defined as Z-scores <= 
      2.0 for those aged < 50 years. For those aged >= 40 years (63.5%), the 10-year
      probabilities of a major fracture (FRAX-Major) and hip fracture (FRAX-Hip) were
      calculated. FRAX-Major >= 20% or Hip >= 3% was considered high risk. HSA was done
      in a subgroup (n = 81) of patients. RESULTS: The study group was 271 women. Mean
      (SD) age was 43.8 (13.1) years and SLE duration was 11.6 (10.4) years. OP was
      diagnosed in 14.6% and LBM in 8.8%. FRAX-Major >= 20% was seen in 9 patients
      (5.3%), of whom 6 were taking OP medications. FRAX-Hip >= 3% occurred in 16
      patients (9.4%), of whom 9 were taking OP medications. Buckling ratio at the left
      hip narrow neck was positively correlated with FRAX-Major, FRAX-Hip, SLE
      duration, and duration of corticosteroid use. CONCLUSION: LBM is prevalent in
      women with SLE who are < 50 years of age. FRAX may identify those at higher risk
      of fractures while HSA can assess bone structure noninvasively.

PMID- 22660813
TI  - Aerobic exercise increases BK(Ca) channel contribution to regulation of
      mesenteric arterial tone by upregulating beta1-subunit.
AB  - Substantial evidence has shown that exercise training produces numerous
      adaptations within the arteries. Large-conductance Ca(2+)-activated K(+) (BK(Ca))
      channels are expressed broadly on smooth muscle cells and play an important role
      in the regulation of vascular tone. The present study was designed to investigate
      the mechanisms by which the BK(Ca) channel underlies the exercise-induced
      improvement of the vascular function in mesenteric arteries. Male Wistar rats
      (180-200 g) were trained for 12 weeks on a treadmill (EX group) and compared with
      age-matched sedentary (SED) animals. Blood pressure and vascular contractility of
      mesenteric arteries were measured. Inside-out patch-clamp recording was applied
      on the freshly separated mesenteric smooth muscle cells to investigate the gating
      characteristics of BK(Ca) channels. Western immunoblotting was performed to study
      expression levels of BK(Ca) channel proteins. The maximal vascular contraction
      induced by noradrenaline (3 * 10(-5) M) was decreased after exercise training.
      Both TEA (3 * 10(-3) M) and iberiotoxin (3 * 10(-8) M) induced a significant
      increase of vessel tension in both SED and EX groups, but these effects were more
      pronounced in EX rats compared with SED animals. Inside-out patch-clamp recording
      showed that exercise training significantly increased the open probability,
      decreased the mean closed time and increased the mean open time and the
      sensitivity to Ca(2+) and voltage without altering the unitary conductance. The
      expression of BK(Ca) beta1- but not alpha-subunit was significantly enhanced
      after exercise training. These data suggest that exercise training increases the
      contribution of the BK(Ca) channel to the regulation of vascular tone in
      mesenteric arteries, which is possibly mediated by upregulating beta1-subunit
      protein to increase BK(Ca) channel activity.

PMID- 22660810
TI  - Colchicine use is associated with decreased prevalence of myocardial infarction
      in patients with gout.
AB  - OBJECTIVE: The ability of antiinflammatory strategies to alter cardiovascular
      risk has not been rigorously examined. Colchicine is an antiinflammatory agent
      that affects macrophages, neutrophils, and endothelial cells, all of which are
      implicated in the pathogenesis of cardiovascular disease. We examined whether
      colchicine use was associated with a reduced risk of myocardial infarction (MI)
      in patients with gout. METHODS: We conducted a retrospective, cross-sectional
      study of all patients with an International Classification of Diseases, 9th ed,
      code for gout in the electronic medical record (EMR) of the New York Harbor
      Healthcare System Veterans Affairs network and >= 1 hospital visit between August
      2007 and August 2008. Hospital pharmacy data were used to identify patients who
      had filled at least 1 colchicine prescription versus those who had not.
      Demographics and CV comorbidities were collected by EMR review. The primary
      outcome was diagnosis of MI. Secondary outcomes included all-cause mortality and
      C-reactive protein (CRP) level. RESULTS: In total, 1288 gout patients were
      identified. Colchicine (n = 576) and no colchicine (n = 712) groups had similar
      baseline demographics and serum urate levels. Prevalence of MI was 1.2% in the
      colchicine versus 2.6% in the no-colchicine group (p = 0.03). Colchicine users
      also had fewer deaths and lower CRP levels, although these did not achieve
      statistical significance. Colchicine effects persisted when allopurinol users
      were excluded from the analysis. CONCLUSION: In this hypothesis-generating study,
      gout patients who took colchicine had a significantly lower prevalence of MI and
      exhibited trends toward reduced all-cause mortality and lower CRP level versus
      those who did not take colchicine.

PMID- 22660812
TI  - Peripheral vascular response to inspiratory breath hold in paediatric homozygous
      sickle cell disease.
AB  - There is increasing evidence that autonomic dysfunction in adults with homozygous
      sickle cell (haemoglobin SS) disease is associated with enhanced autonomic
      nervous system-mediated control of microvascular perfusion. However, it is
      unclear whether such differences are detectable in children with SS disease. We
      studied 65 children with SS disease [38 boys; median age 7.2 (interquartile range
      5.1-10.6) years] and 20 control children without symptoms of SS disease [8 boys;
      8.7 (5.5-10.8) years] and recorded mean arterial blood pressure (ABP) and daytime
      haemoglobin oxygen saturation (S(pO(2))). Cutaneous blood flux at rest (RBF) and
      during the sympathetically activated vasoconstrictor response to inspiratory
      breath hold (IBH) were measured in the finger pulp of the non-dominant hand using
      laser Doppler fluximetry. Local factors mediating flow motion were assessed by
      power spectral density analysis of the oscillatory components of the laser
      Doppler signal. The RBF measured across the two study groups was negatively
      associated with age (r = -0.25, P < 0.0001), ABP (r = -0.27, P = 0.02) and
      daytime S(pO(2)) (r = -0.30, P = 0.005). Children with SS disease had a higher
      RBF (P = 0.005) and enhanced vasoconstrictor response to IBH (P = 0.002) compared
      with control children. In children with SS disease, higher RBF was associated
      with an increase in the sympathetic interval (r = -0.28, P = 0.022). The SS
      disease status, daytime S(pO(2)) and age explained 22% of the variance in
      vasoconstrictor response to IBH (P < 0.0001). Our findings suggest that blood
      flow and blood flow responses in the skin of young African children with SS
      disease differ from those of healthy control children, with increased resting
      peripheral blood flow and increased sympathetic stimulation from a young age in
      SS disease. They further suggest that the laser Doppler flowmetry technique with
      inspiratory breath hold manoeuvre appears to be robust for use in young children
      with SS disease, to explore interactions between S(pO(2)), ABP and autonomic
      function with clinical complications, e.g. skin ulceration.

PMID- 22660814
TI  - The dorsal motor nucleus of the vagus and regulation of pancreatic secretory
      function.
AB  - Recent investigation of the factors and pathways that are involved in regulation
      of pancreatic secretory function (PSF) has led to development of a pancreatic
      vagovagal reflex model. This model consists of three elements, including
      pancreatic vagal afferents, the dorsal motor nucleus of the vagus (DMV) and
      pancreatic vagal efferents. The DMV has been recognized as a major component of
      this model and so this review focuses on the role of this nucleus in regulation
      of PSF. Classically, the control of the PSF has been viewed as being dependent on
      gastrointestinal hormones and vagovagal reflex pathways. However, recent studies
      have suggested that these two mechanisms act synergistically to mediate
      pancreatic secretion. The DMV is the major source of vagal motor output to the
      pancreas, and this output is modulated by various neurotransmitters and synaptic
      inputs from other central autonomic regulatory circuits, including the nucleus of
      the solitary tract. Endogenously occurring excitatory (glutamate) and inhibitory
      amino acids (GABA) have a marked influence on DMV vagal output to the pancreas.
      In addition, a variety of neurotransmitters and receptors for gastrointestinal
      peptides and hormones have been localized in the DMV, emphasizing the direct and
      indirect involvement of this nucleus in control of PSF.

PMID- 22660825
TI  - Neighborhood processes, self-efficacy, and adolescent mental health.
AB  - Self-efficacy beliefs are central to mental health. Because adolescents'
      neighborhoods shape opportunities for experiences of control, predictability, and
      safety, we propose that neighborhood conditions are associated with adolescents'
      self-efficacy and, in turn, their internalizing problems (i.e.,
      depression/anxiety symptoms). We tested these hypotheses using three waves of
      data from the Project on Human Development in Chicago Neighborhoods (N = 2,345).
      Results indicate that adolescents living in violent neighborhoods tended to
      report lower self-efficacy beliefs, partly because they were more likely to
      experience fear in their neighborhood. However, moving out of Chicago
      neighborhoods marked by violence and low collective efficacy to neighborhoods
      outside of the city was associated with adolescents' increased self-efficacy (vs.
      staying in such neighborhoods), an association explained by adolescents' school
      related experiences. Finally, through self-efficacy, these neighborhood processes
      had an indirect association with adolescents' internalizing problems. Results
      partially support a model linking neighborhood conditions, cognitions about the
      self, and emotions.

PMID- 22660826
TI  - Social network resources and management of hypertension.
AB  - Hypertension is one of the most prevalent chronic diseases among older adults,
      but rates of blood pressure control are low. In this article, we explore the role
      of social network ties and network-based resources (e.g., information and
      support) in hypertension diagnosis and management. We use data from the National
      Social Life, Health, and Aging Project to identify older adults with undiagnosed
      or uncontrolled hypertension. We find that network characteristics and emotional
      support are associated with hypertension diagnosis and control. Importantly, the
      risks of undiagnosed and uncontrolled hypertension are lower among those with
      larger social networks-if they discuss health issues with their network members.
      When these lines of communication are closed, network size is associated with
      greater risk for undiagnosed and uncontrolled hypertension. Health care
      utilization partially mediates associations with diagnosis, but the benefits of
      network resources for hypertension control do not seem to stem from health
      related behaviors.

PMID- 22660827
TI  - Neighborhood social capital, parenting strain, and personal mastery among female
      primary caregivers of children.
AB  - Neighborhood social capital-resources inherent within community networks-has been
      identified as a potential facilitator of personal well-being. We test hypotheses
      concerning how neighborhood social capital moderates the influence of parenting
      strain on mastery (individuals' understanding of their ability to control
      personal life circumstances) for female primary caregivers of children. First, we
      test how different forms of neighborhood social capital-social support, social
      leverage (information exchange), informal social control, and neighborhood
      organization participation-modify the association between parenting strain and
      mastery. Second, we test whether such moderation depends on one's access to these
      forms via neighbor ties. Analyses of Los Angeles Family and Neighborhood Survey
      data (N = 765) indicate that the negative relationship between parenting strain
      and mastery worsens as informal social control increases. Social support and
      informal social control, however, buffer this parenting strain-mastery
      relationship when caregivers have stronger ties to neighbors. Our findings
      implicate mechanisms of "negative social capital" and warrant more nuanced
      considerations of neighborhood social capital's health-promoting potential.

PMID- 22660828
TI  - Union transitions and changes in BMI among adults in Mexico.
AB  - This study utilizes nationally representative, longitudinal data from the Mexico
      Family Life Survey to examine the associations between union transitions and
      changes in body mass index (BMI) among adults in Mexico. Results from change
      score regression models (N = 11,339) indicate larger BMI gains for those entering
      a union than for those remaining single, net of baseline weight status and
      socioeconomic controls. Further, a significant moderating effect of baseline
      weight status suggests that overweight individuals entering a union gain almost
      two BMI points more than overweight single individuals during this three-year
      period. Individuals experiencing a union dissolution gain less BMI than those
      entering a union, but are predicted to lose BMI (as found in the United States)
      only if they are overweight before the transition.

PMID- 22660834
TI  - Assessing calcareous sponges and their associated bacteria for the discovery of
      new bioactive natural products.
AB  - An overview of the chemistry and microbiology of calcareous sponges
      (Calcispongiae) is provided, highlighting the potential of these sessile filter
      feeding marine invertebrates and their associated bacteria for the discovery of
      new bioactive natural products. 103 compounds are presented and 116 references
      cited.

PMID- 22660835
TI  - Mental disorders: employment and work productivity in Singapore.
AB  - AIM: To examine the association between mental disorders and work disability in
      the adult resident population in Singapore. METHOD: Data are from the Singapore
      Mental Health Study, which was a household survey of a nationally representative
      sample. The main instrument used was the Composite International Diagnostic
      Interview (CIDI). Employment-related information was collected using the modified
      employment module of the CIDI. RESULTS: A total of 6,429 respondents were
      included in the analysis, 71 % (n = 4,594) were employed, 24.5 % (n = 1,522) were
      economically inactive and 4.5 % (n = 313) were unemployed. Among the employed,
      2.3 % had a 12-month prevalence of at least one mental disorder, while 5.3 % of
      the unemployed had at least one mental disorder. The average number of work loss
      days (absenteeism) per capita among those with a mental disorder was 0.5 per
      month that is equivalent to an annualized national projection of approximately
      0.3 million productivity days. The average work-cutback days (presenteeism) were
      0.4 days among this group. Of the mentally ill in the workforce, a high
      proportion (86.5 %) did not ever seek help for problems related to mental health.
      CONCLUSION: Our findings provide information on the significant consequences of
      mental disorders on the workforce in terms of lost work productivity, which could
      pave the way for a more rational allocation of scarce resources.

PMID- 22660836
TI  - Pleomorphic hyalinizing angiectatic tumor: imaging findings.
AB  - Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare soft tissue tumor of
      low malignant potential, which most often arises in the lower extremities. To the
      best of our knowledge, there have been no prior descriptions of the imaging
      features of this neoplasm. In this case series, we report the imaging findings in
      three patients. Two patients had a lower extremity subcutaneous PHAT, while the
      third patient had an intramuscular upper extremity PHAT. While imaging features
      are variable, a diagnosis of PHAT should be considered when encountering an
      enhancing, subcutaneous tumor with ill-defined margins, particularly in the
      extremity.

PMID- 22660837
TI  - 3-T MRI assessment of osteophyte formation in patients with unilateral anterior
      cruciate ligament injury and reconstruction.
AB  - OBJECTIVE: To define the number and distribution of osteophytes (OPs) in
      bilateral knee MRI (magnetic resonance imaging) of patients with unilateral
      anterior cruciate ligament (ACL) rupture. MATERIALS AND METHODS: Bilateral knee
      MRIs of 20 patients with unilateral ACL rupture and reconstruction were
      retrospectively analyzed for OPs. OPs were graded following the KOSS (knee OA
      scoring system) classification and their compartmental distribution was assessed
      following the WORMS (Whole-Organ Magnetic Resonance Imaging Score)
      classification. RESULTS: All examined knees revealed OPs. Knees with ACL rupture
      showed significant (p < 0.001) higher total numbers of OPs (mean 11.6; SD +/-
      4.4) than knees with intact ACL (mean 5.1; SD +/- 2.3). Knees with ACL rupture
      showed increased OP formation in all knee compartments with predominance of
      marginal OPs in the lateral femorotibial compartment especially on the tibia.
      CONCLUSIONS: Our results show that after knee injury with ACL rupture and
      reconstruction, all knee compartments were involved in post-traumatic increase of
      OP formation. The most affected compartment was the lateral femorotibial
      compartment on the tibial side.

PMID- 22660839
TI  - Comparison of surgical plume among laparoscopic ultrasonic dissectors using a
      real-time digital quantitative technology.
AB  - BACKGROUND: This study aimed to analyze the effect of surgical plume generation
      from various ultrasonic dissectors on laparoscopic visibility, including the
      first cordless ultrasonic dissector, using a novel real-time digital
      quantification technique. METHODS: The Covidien Cordless Sonicision, the Harmonic
      ACE, and the Olympus SonoSurg were applied to bovine liver with industry
      specified settings. Consecutive activations were digitally captured from a
      laparoscope positioned to replicate the clinical setting. Plume was recognized by
      ImageJ software, and the percentage of pixels containing plume in each video
      frame was calculated. Analysis of variance statistical multi-analysis and Welch's
      t test were computed for all p values. RESULTS: The average maximum plume
      produced by the Sonicision, ACE, and SonoSurg with the maximum setting were
      respectively 8.76% (range, 4.32-17.41%), 18.04% (range, 9.07-55.12%), and 9.46%
      (range, 5.68-22.12%) (p = 0.026). The deviations between the ACE and the other
      devices were significant (p < 0.05). The average maximum plumes produced with the
      coagulation setting were 4.80% (range, 0.24-19.83%) for the Sonicision, 26.63%
      (range, 8.12-73.50%) for the ACE, and 0.21% (range, 0.06-1.05%) for the SonoSurg
      (p < 0.001). The differences between all the instruments in the coagulation
      setting were significant. CONCLUSION: To the authors' knowledge, this is the
      first report on a real-time digital analysis of surgical plume generation using
      ImageJ software. In the coagulation setting, the SonoSurg generated minimal
      plume. The Sonicision obstructed approximately 4%, whereas the ACE generated
      plume that obstructed 25% of the laparoscopic field. In the cutting setting, the
      SonoSurg and Sonicision generated the least obstruction, whereas the ACE caused
      the most obstruction.

PMID- 22660838
TI  - Modulatory effects of Pycnogenol in a rat model of insulin-dependent diabetes
      mellitus: biochemical, histological, and immunohistochemical evidences.
AB  - A number of experimental and clinical findings have consistently demonstrated the
      protective effects of Pycnogenol (PYC) in the management of diabetes. However,
      the protective mechanism by which PYC provides protection in a model type I
      diabetes has not been studied. This study examines the beneficial effect of PYC
      on hyperglycemia, inflammatory markers, and oxidative damage in diabetic rats. We
      also evaluated the possible mechanism of action of PYC which might be that it
      stimulates beta islet expression, which has been implicated in the process of
      insulin secretion and diabetes management. Diabetes was induced in rats by an
      intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight) followed
      by free access to 5 % glucose for the next 24 h. Four days after STZ injection,
      rats were supplemented with PYC (10 mg/kg body weight) for 4 weeks. At the end of
      the experiment, blood was drawn, and rats were then sacrificed, and their livers
      and pancreases were dissected for biochemical and histological assays. The level
      of fasting blood glucose and glycosylated hemoglobin significantly increased but
      amylase, insulin, and hepatic glycogen level decreased in the STZ group. PYC
      significantly augmented these effects in STZ + PYC group. The STZ group showed
      elevated level of nitric oxide, tumor necrosis factor-alpha, and interleukin
      1beta in serum which were decreased by PYC treatment. Moreover, PYC significantly
      ameliorated increased thiobarbituric reactive substances, protein carbonyl, and
      decreased levels of glutathione, glutathione-s-transferase, and catalase activity
      in the liver and pancreas of the STZ rats. Histopathological and
      immunohistochemical examination also revealed a remarkable protective effect of
      PYC. The study suggests that PYC is effective in reducing diabetic-related
      complications in a type I model of diabetes and might be beneficial for the
      treatment of diabetic patients.

PMID- 22660840
TI  - Genetic and structural characterization of the growth hormone gene and protein
      from tench, Tinca tinca.
AB  - The analysis of the tench growth hormone gene structure revealed a comparable
      organization of coding and non-coding regions than other from cyprinid species.
      Based on the performed mRNA and amino acid sequence alignments, gh tench is
      related to Asian than to European representatives of Cyprinidae family. Second
      aim of the work was to characterize and predict protein structure of the tench
      growth hormone. Tinca tinca GH share many common features with human GH molecule.
      The Tench GH protein binds to the growth hormone receptor (GHR) using two regions
      I and II that are situated at opposite sites of molecule. Binding site I is
      placed in the central part of T. tinca GH and H 189 amino acid in the middle
      region of the IV helix is crucial for GH-GHR interactions.

PMID- 22660850
TI  - Breathing resistance and ultrafine particle deposition in nasal-laryngeal airways
      of a newborn, an infant, a child, and an adult.
AB  - As a human grows from birth to adulthood, both airway anatomy and breathing
      conditions vary, altering the deposition rate and pattern of inhaled aerosols.
      However, deposition studies have typically focused on adult subjects, results of
      which may not be readily extrapolated to children. This study numerically
      evaluated the age-related effects on the airflow and aerosol dynamics in image
      based nose-throat models of a 10-day-old newborn, a 7-month-old infant, a 5-year
      old child, and a 53-year-old adult. Differences in airway physiology, breathing
      resistance, and aerosol filtering efficiency among the four models were
      quantified and compared. A high-fidelity fluid-particle transport model was
      employed to simulate the multi-regime airflows and particle transport within the
      nasal-laryngeal airways. Ultrafine particles were evaluated under breathing
      conditions ranging from sedentary to heavy activities. Results of this study
      indicate that the nasal-laryngeal airways at different ages, albeit differ
      significantly in morphology and dimension, do not significantly affect the total
      deposition fractions or maximum local deposition enhancement for ultrafine
      aerosols. Further, the deposition partitioning in the sub-regions of interest is
      different among the four models. Results of this study corroborate the use of the
      in vivo-based diffusion parameter (D(0.5)Q(-0.28)) over the replica-based
      parameter in correlating nasal-laryngeal depositions of ultrafine aerosols.
      Improved correlations have been developed for the four age groups by implementing
      this in vivo-based diffusion parameter as well as the Cunningham correction
      factor.

PMID- 22660842
TI  - Validation of the Revised Individual Placement and Support Fidelity Scale (IPS
      25).
AB  - OBJECTIVE: The individual placement and support (IPS) model of supported
      employment for people with severe mental illness is an evidence-based practice.
      The 15-item IPS Fidelity Scale (IPS-15) was developed to measure program fidelity
      and has been shown to have good psychometric properties, including predictive
      validity. On the basis of field experience and research updates, the authors
      developed an expanded and revised version of this scale, the IPS-25, also known
      as the Supported Employment Fidelity Scale. This study evaluated the psychometric
      properties of the IPS-25. METHODS: In addition to data on the local unemployment
      rate and program longevity, the authors collected IPS-25 ratings and employment
      data for 79 sites in eight states participating in a learning collaborative
      devoted to implementing the IPS model. Descriptive data for items and the total
      scale and predictive validity were examined. RESULTS: Internal consistency
      reliability for the IPS-25 was .88. Predictive validity, measured as the
      correlation between the IPS-25 and site-level employment rate, was .34. Eight of
      the IPS-25 items were significantly positively correlated with employment rate.
      Items related to the vocational generalist role, disclosure, follow-along
      support, and vocational unit were the most strongly correlated with employment.
      Program longevity was positively associated with employment, whereas the
      unemployment rate was not. CONCLUSIONS: The IPS-25 has promising psychometric
      properties, with greater precision and content coverage than the IPS-15. However,
      it has not demonstrated an advantage over the IPS-15 in predictive validity.
      Research directly comparing the two scales is needed.

PMID- 22660841
TI  - Syndecan-4 cytoplasmic domain regulation of turkey satellite cell focal adhesions
      and apoptosis.
AB  - Syndecan-4 is a cell membrane proteoglycan composed of a transmembrane core
      protein and substituted glycosaminoglycan (GAG) and N-linked glycosylated (N
      glycosylated) chains. The core protein has three domains: extracellular,
      transmembrane and cytoplasmic domains. The GAG and N-glycosylated chains and the
      cytoplasmic domain of syndecan-4, especially the amino acids: Ser(178) and
      Tyr(187) are critical in regulation of turkey satellite cell growth and
      development. How these processes are regulated is still unknown. The objective of
      the current study was to determine whether the syndecan-4 GAG and N-glycosylated
      chains and the cytoplasmic domain functions through modulating focal adhesion
      formation and apoptosis. Twelve mutant clones were generated: a truncated
      syndecan-4 without the cytoplasmic domain with or without GAG and N-glycosylated
      chains, and Ser(178) and Tyr(187) mutants with or without GAG and N-glycosylated
      chains. The wild type syndecan-4 and all of the syndecan-4 mutants were
      transfected into turkey myogenic satellite cells after which cell apoptosis and
      focal adhesion formation were measured. Syndecan-4 increased cell membrane
      localization of beta1 integrin and the activity of focal adhesion kinase (FAK)
      whereas the cytoplasmic domain mutation decreased the phosphorylation of FAK.
      However, syndecan-4 and syndecan-4 mutants did not influence cell apoptosis. They
      also had no effect on vinculin or paxillin-containing focal adhesion formation.
      These results suggested that the syndecan-4 cytoplasmic domain plays an important
      role in regulating FAK activity and beta1 integrin cell membrane localization but
      not cell apoptosis and vinculin or paxillin-containing focal adhesion formation.

PMID- 22660851
TI  - PGP 9.5 distribution patterns in biopsies from early lesions of atopic
      dermatitis.
AB  - Peripheral nerve fibres are often increased in lesional skin of atopic dermatitis
      (AD) patients. We attempted to study nerve fibre profiles, using PGP 9.5 as
      neuronal marker, in early AD lesions in 10 patients, as compared to non-lesional
      skin in the same patients and skin from healthy controls. The number of PGP 9.5
      positive nerve fibre profiles was not different in the biopsies taken from normal
      looking AD skin and healthy controls. The total number of PGP 9.5-positive nerve
      fibre profiles in the whole skin sections was higher in both the epidermis and
      the dermis in the group of skin biopsies taken from early lesions of AD patients.
      Further, the number of epidermal PGP 9.5-positive dendritic cells was increased
      in AD skin. It seems reasonable that PGP 9.5-positive nerve fibres and PGP 9.5
      positive dendritic cells have pathological roles in AD. The findings might serve
      as a basis for further studies in evaluating novel diagnostic and therapeutic
      approaches.

PMID- 22660853
TI  - Designing studies to meet the task.

PMID- 22660852
TI  - Two-patch population models with adaptive dispersal: the effects of varying
      dispersal speeds.
AB  - The population-dispersal dynamics for predator-prey interactions and two
      competing species in a two patch environment are studied. It is assumed that both
      species (i.e., either predators and their prey, or the two competing species) are
      mobile and their dispersal between patches is directed to the higher fitness
      patch. It is proved that such dispersal, irrespectively of its speed, cannot
      destabilize a locally stable predator-prey population equilibrium that
      corresponds to no movement at all. In the case of two competing species,
      dispersal can destabilize population equilibrium. Conditions are given when this
      cannot happen, including the case of identical patches. 

PMID- 22660854
TI  - Use of teat sealants at agricultural shows.

PMID- 22660855
TI  - Polioencephalo-myelitis in a calf due to infection with Schmallenberg virus.

PMID- 22660856
TI  - Respiratory disease due to acute Sarcocystis tenella infection in sheep.

PMID- 22660857
TI  - Religious slaughter in context.

PMID- 22660866
TI  - CT, MRI, and PET findings of gastric schwannoma.
AB  - Gastric schwannoma is a rare tumor that accounts for only 0.2 % of all gastric
      tumors. We report a case of gastric schwannoma that underwent computed tomography
      (CT), magnetic resonance imaging (MRI), and [(18)F]-fluorodeoxyglucose positron
      emission tomography (FDG-PET), and its histological confirmation was acquired.
      Gastric schwannoma showed high intensity on T2-weighted and diffusion-weighted
      MRI and high maximum standardized uptake on [(18)F]-FDG-PET. Lymphadenopathy
      close to the tumor was also found. Although diffusion-weighted MRI, [(18)F]-FDG
      PET, and the presence of lymphadenopathy could suggest malignant tumors, the
      detail interpretation of the other CT and MRI findings may give a clue for the
      diagnosis of gastric schwannoma.

PMID- 22660867
TI  - Fire, skin, and fat: inflammation, psoriasis, and cardiovascular disease.

PMID- 22660868
TI  - The apples and oranges of cost-effectiveness.

PMID- 22660869
TI  - Anemia, leukocytosis, abdominal pain, flushing, and bone and skin lesions.

PMID- 22660870
TI  - Acute community-acquired bacterial meningitis in adults: an evidence-based
      review.
AB  - Community-acquired bacterial meningitis is still a significant cause of morbidity
      and mortality. Clinicians should know how to quickly diagnose it, perform a
      lumbar puncture, order the necessary tests, and start appropriate empiric therapy
      promptly.

PMID- 22660871
TI  - Sudden hypoxia during knee surgery.

PMID- 22660872
TI  - Superior vena cava syndrome.

PMID- 22660873
TI  - Psoriasis: evolving treatment for a complex disease.
AB  - The cutaneous manifestations of psoriasis can vary in morphology and severity,
      and therapy should be tailored accordingly. Biologic agents are important new
      options for treating patients with the most severe forms of the disease. All
      physicians should be aware that severe psoriasis may increase cardiovascular
      morbidity and the risk of death, and preventive strategies for patients with
      severe disease should be considered.

PMID- 22660874
TI  - A skin lesion after cardiac catheterization.

PMID- 22660875
TI  - UV protection and sunscreens: what to tell patients.
AB  - Ultraviolet (UV) radiation is the major environmental risk factor for nonmelanoma
      skin cancer and is a suspected risk factor for melanoma. Avoiding overexposure to
      direct sunlight during the peak daylight hours, wearing protective clothing, and
      applying sunscreen are ways to protect the skin. To provide clinicians with the
      tools to advise patients and to answer their inquiries, including which sunscreen
      to use, we review UV radiation's effect on the skin, how sunscreens block UV
      light, current recommendations on sunscreen use, and new sunscreen labeling
      requirements.

PMID- 22660876
TI  - Patient information. How to avoid damaging ultraviolet light.

PMID- 22660886
TI  - Three-dimensional knee joint loading in alpine skiing: a comparison between a
      carved and a skidded turn.
AB  - Limited data exists on knee biomechanics in alpine ski turns despite the high
      rate of injuries associated with this maneuver. The purpose of the current study
      was to compare knee joint loading between a carved and a skidded ski turn and
      between the inner and outer leg. Kinetic data were collected using Kistler mobile
      force plates. Kinematic data were collected with five synchronized, panning,
      tilting, and zooming cameras. Inertial properties of the segments were calculated
      using an extended version of the Yeadon model. Knee joint forces and moments were
      calculated using inverse dynamics analysis. The obtained results indicate that
      knee joint loading in carving is not consistently greater than knee joint loading
      in skidding. In addition, knee joint loading at the outer leg is not always
      greater than at the inner leg. Differentiation is required between forces and
      moments, the direction of the forces and moments, and the phase of the turn that
      is considered. Even though the authors believe that the analyzed turns are
      representative, results have to be interpreted with caution due to the small
      sample size.

PMID- 22660887
TI  - Chronic disfiguring facial lesions in an immunocompetent patient due to Exophiala
      spinifera: a case report and review of literature.
AB  - Exophiala spinifera is a rare fungus causing chromoblastomycosis or different
      types of phaeohyphomycosis (cutaneous, subcutaneous, disseminated and cyst
      phaeohyphomycosis). We report a case of a young male with phaeohyphomycosis due
      to E. spinifera, who had multiple itchy painful papular lesions disfiguring his
      face for 4 years. His diagnosis was delayed and had received antibacterial and
      antileishmanial therapy elsewhere without any improvement. While he reported to
      our hospital, the histopathology of the biopsy collected from the lesion
      demonstrated acute on chronic inflammation with granuloma formation and darkly
      pigmented fungal elements. The isolate grown on culture was identified as E.
      spinifera on the basis of morphological characters. The identification of the
      isolate was further confirmed by sequencing of the ITS region of ribosomal DNA.
      After treatment with oral itraconazole, he had marked clinical improvement.

PMID- 22660889
TI  - The prevalence of preterm births in pregnancies complicated with fetal
      gastroschisis.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of preterm
      births in pregnancies complicated by fetal gastroschisis in our tertiary referral
      center. METHODS: We conducted a retrospective review of medical records of
      patients with fetal gastroschisis delivered at our institution between January
      2004 and April 2012. RESULTS: A total of 63 patients met the study criteria. Of
      these, 32 (51 %) were delivered before 37 0/7 weeks of gestation. The mean
      estimated gestational age at delivery was 35 4/7 +/- 1 week (range 32 6/7-36 6/7)
      weeks. Spontaneous preterm delivery occurred in 27 patients (43 %). The remaining
      31 patients (49 %) delivered between 37 0/7 and 39 2/7 weeks of gestation.
      CONCLUSION: The majority of patients with fetal gastroschisis were delivered
      before 37 weeks of gestation with a significant proportion delivering due to
      spontaneous onset of preterm labor. In addition to antepartum surveillance for
      fetal well-being, monitoring patients for symptoms and signs of preterm labor is
      recommended.

PMID- 22660888
TI  - Parents' perceptions of benefit of children's mental health treatment and
      continued use of services.
AB  - OBJECTIVE: The authors examined the association of demographic and clinical
      characteristics, family history, and type of treatment among children receiving
      outpatient mental health services and parents' perception of treatment benefit.
      They also examined whether perceived benefit was related to continued use of
      services at six-month follow-up. METHODS: Parents of children age six to 12 years
      who were first-time patients at one of nine clinics participating in the
      Longitudinal Assessment of Manic Symptoms (LAMS) study completed the Parent
      General Behavior Inventory Ten-Item Mania Scale. Parents of children with scores
      of 12 or higher (N=1,124) were invited to participate in a follow-up study, and
      621 agreed. During baseline assessment after the first outpatient visit and at
      six-month follow-up, the parents were asked about children's sociodemographic and
      diagnostic characteristics and use of services and asked to rate how much their
      children had benefited from the most recent outpatient treatment. RESULTS: Data
      were available for 573 children. At baseline, parents of 167 (29%) children
      reported that the treatment provided a lot of benefit, and perceived benefit was
      related to receiving medication (with or without therapy) versus just therapy,
      higher scores on functioning, LAMS site, no history of comorbid diagnoses, living
      with both biological parents, and having no parents or siblings with a prior
      hospitalization for a psychiatric illness. At six-month follow-up, perceived
      benefit was related to continued use of services (p<.001). CONCLUSIONS:
      Medication with or without therapy was perceived as more beneficial than therapy
      alone. Perceived benefit was strongly related to continued use of treatment.

PMID- 22660890
TI  - Physiological responses of great sturgeon (Huso huso) to different concentrations
      of 2-phenoxyethanol as an anesthetic.
AB  - The objective of the study was to evaluate the efficacy of 2-phenoxyethanol (2
      PE) as an anesthetic in great sturgeon under two experiments. First, fish were
      exposed to 0.1, 0.3, 0.5, 0.7 and 0.9 mL/L 2-PE, and time to induction (deep
      anesthesia) and recovery from anesthesia were measured. At concentration of 0.1
      mL/L, 2-PE failed to induce deep anesthesia in fish, whereas at concentrations of
      0.7 and 0.9 mL/L, all the fish were anaesthetized within 3 min of exposure. For
      assessing the impact of effective concentrations of 2-PE on physiological
      responses of great sturgeon, hematological indices, plasma metabolites,
      electrolytes, enzymes and cortisol levels were measured. The use of 2-PE induces
      a significant increase in RBC values at 0.3 mL/L concentration and a parallel
      increase in hemoglobin and hematocrit values. 2-PE anesthesia had no effect on
      WBC, MCV, MCH and MCHC levels when compared to control group. Serum glucose,
      cholesterol and cortisol levels were significantly high in 0.3 and 0.5 mL/L 2-PE.
      Moreover, AST levels were increased in fish exposed to the 0.3 mL/L 2-PE
      comparing with the control group (P < 0.05). There were no significant
      differences in serum levels of total protein, triglycerides, ALP, ALT, Cl(-),
      Na(+), K(+), Ca(2+) and Mg(2+). In this study, alteration in hematological and
      serum biochemical indices was time-dependent. This study demonstrates that rapid
      induction of deep anesthesia with a relatively high concentration of 2-PE (0.7
      and 0.9 mL/L) was associated with the lowest effects on the hematological and
      serum biochemical indices in great sturgeon and therefore would be recommended as
      eligible doses for hematological studies in this species.

PMID- 22660891
TI  - Establishment and characterization of a new fish cell line from head kidney of
      half-smooth tongue sole (Cynoglossus semilaevis).
AB  - A new cell line (TSHKC) derived from half-smooth tongue sole (Cynoglossus
      semilaevis) head kidney was developed. The cell line was subcultured for 40
      passages over a period of 360 days. The cell line was optimally maintained in
      minimum essential medium supplemented with HEPES, antibiotics, fetal bovine
      serum, 2-Mercaptoethanol (2-Me), sodium pyruvate and basic fibroblast growth
      factor. The suitable growth temperature for TSHKC cells was 24  degrees C, and
      microscopically, TSHKC cells were composed of fibroblast-like cells. Chromosome
      analysis revealed that the TSHKC cell line had a normal diploid karyotype with 2n
      = 42, contained the heterogametic W chromosome. The TSHKC cell line was found to
      be susceptible to lymphocystis disease virus. The fluorescent signals were
      observed in TSHKC when the cells were transfected with green fluorescent protein
      and red fluorescent protein reporter plasmids.

PMID- 22660892
TI  - Annual variation of hematology and plasma chemistry in shortnose sturgeon,
      Acipenser brevirostrum, during a dam-impeded spawning run.
AB  - Shortnose sturgeon (Acipenser brevirostrum) spawning migrations on the Cooper
      River are impeded by Pinopolis Dam, Lake Moultrie, South Carolina. Sturgeon and
      other species aggregate below the dam in late winter/early spring and are
      subjected to a variety of stressors stemming from crowding, poor habitat quality,
      and injuries that appear to be caused by boat propeller or turbine strikes.
      Spawning has been documented in the tailrace, but reproductive success has not
      been verified as no juveniles have been captured. Fish within the dam tailrace
      were captured by gill net during winter, 2005 and 2007-2011, and physiological
      condition was assessed using a panel of hematologic and biochemical indices.
      Plasma phosphorus and calcium were significantly higher in females, while PCV and
      aspartate aminotransferase were significantly higher in males, indicating sex
      specific physiological changes triggered during maturity. A marked leucopenia,
      accompanied by lymphopenia and neutrophilia, was evident in both sexes and was
      consistent across years, indicating that these fish were under chronic stress.
      Testosterone and estradiol levels and hematologic and biochemical reference
      intervals are provided for comparative purposes.

PMID- 22660893
TI  - Hybrid solar cells from MDMO-PPV and silicon nanocrystals.
AB  - Solution-processed bulk heterojunction solar cells from silicon nanocrystals (Si
      NCs) and poly(3-hexylthiophene) (P3HT) have shown promising power conversion
      efficiencies. Here we report on an attempt to enhance the performance of Si NC
      polymer hybrid solar cells by using poly[2-methoxy-5-(3',7'-dimethyloctyloxy)-1,4
      phenylenevinylene] (MDMO-PPV) as a hole conductor, which is expected to yield a
      higher open circuit voltage than P3HT due to its lower highest occupied molecular
      orbital (HOMO). Bulk heterojunction solar cells consisting of 3-5 nm silicon
      nanocrystals (Si NCs) and poly[2-methoxy-5-(3',7'-dimethyloctyloxy)-1,4
      phenylenevinylene] (MDMO-PPV) have been fabricated. The properties of the hybrid
      Si NC/MDMO-PPV devices were studied as a function of the Si NC/MDMO-PPV weight
      ratio. Cells of 58 wt% 3-5 nm Si NCs showed the best overall performance under
      simulated one-sun AM 1.5 global illumination (100 mW cm(-2)). Compared to
      composite films of Si NCs and poly(3-hexylthiophene), we indeed observed an
      improved open circuit voltage but a lower power conversion efficiency from the Si
      NC/MDMO-PPV devices. The lower efficiency of Si NC/MDMO-PPV is correlated to the
      lower hole mobility and narrower absorption spectrum of MDMO-PPV compared to
      P3HT.

PMID- 22660894
TI  - Lactate stimulates angiogenesis and accelerates the healing of superficial and
      ischemic wounds in mice.
AB  - Wounds notoriously accumulate lactate as a consequence of both anaerobic and
      aerobic glycolysis following microcirculation disruption, immune activation, and
      increased cell proliferation. Several pieces of evidence suggest that lactate
      actively participates in the healing process through the activation of several
      molecular pathways that collectively promote angiogenesis. Lactate indeed
      stimulates endothelial cell migration and tube formation in vitro, as well as the
      recruitment of circulating vascular progenitor cells and vascular morphogenesis
      in vivo. In this study, we examined whether the pro-angiogenic potential of
      lactate may be exploited therapeutically to accelerate wound healing. We show
      that lactate delivered from a Matrigel matrix improves reperfusion and opposes
      muscular atrophy in ischemic hindlimb wounds in mice. Both responses involve
      lactate-induced reparative angiogenesis. Using microdialysis and enzymatic
      measurements, we found that, contrary to poly-L-lactide (PLA), a subcutaneous
      implant of poly-D,L-lactide-co-glycolide (PLGA) allows sustained local and
      systemic lactate release. PLGA promoted angiogenesis and accelerated the closure
      of excisional skin wounds in different mouse strains. This polymer is FDA
      approved for other applications, emphasizing the possibility of exploiting PLGA
      therapeutically to improve wound healing.

PMID- 22660896
TI  - What can cognitive neuroscience teach us about anorexia nervosa?
AB  - Anorexia nervosa (AN) is a complex illness and highly challenging to treat. One
      promising approach to significantly advance our understanding of the underlying
      pathophysiology of AN involves developing a cognitive neuroscience model of
      illness. Cognitive neuroscience uses probes such as neuropsychological tasks and
      neuroimaging techniques to identify the neural underpinnings of behavior. With
      this approach, advances have been made in identifying higher-order cognitive
      processes that likely mediate symptom expression in AN. Identification of related
      neuropathology is beginning. Such findings led to the development of complex
      neurobehavioral models that aim to explain the etiology and persistence of AN.
      Future research will use these advanced tools to test and refine hypotheses about
      the underlying mechanisms of AN.

PMID- 22660895
TI  - Oxidative stress in hypertensive children before and after 1 year of
      antihypertensive therapy.
AB  - BACKGROUND: The relation between primary hypertension (PH), target organ damage
      (TOD) and oxidative stress (SOX) is not known. METHODS: We assessed SOX in 86
      children with PH before and after 12 months of standard non-pharmacological and
      pharmacological therapy based on renin-angiotensin system blockade. RESULTS:
      Patients with left ventricular hypertrophy (LVH) and with carotid intima-media
      thickness (cIMT) >2SDS had higher thiobarbituric acid reactive substances (TBARS)
      concentrations in comparison to patients without LVH or with normal cIMT.
      Patients with metabolic syndrome (MS) had lower activity of gluthatione
      peroxidase, higher asymmetric dimethyloarginine (ADMA) and oxidized LDL
      cholesterol (oxyLDL) in comparison to patients without MS. TBARS correlated with
      left ventricular concentric hypertrophy, cIMT, albuminuria and SBP/24 h. ADMA and
      oxyLDL correlated with CRP and TG/HDL ratio. After 1 year of antihypertensive
      treatment blood pressure, TOD and prevalence of MS decreased. TBARS decreased and
      glutathione concentrations increased. The decrease of TBARS concentration
      correlated with the decrease of body mass index (BMI). Decrease of oxyLDL and
      ADMA correlated with increased insulin sensitivity, however markers of SOX did
      not correlate with BP decrease. CONCLUSION: SOX in children with PH correlates
      with TOD, metabolic abnormalities, changes in fat amount and improvement of
      insulin sensitivity, but not with BP decrease.

PMID- 22660897
TI  - Alcohol and substance misuse in older adults.
AB  - With the "Baby Boom" cohort reaching the age of 65 years, the older adult
      population is growing and will continue to grow at a rapid rate. There is a
      substantial and growing number of older adults who misuse alcohol, psychoactive
      prescription drugs, and/or other substances. The emerging literature on the
      cohort of aging adults indicates that they are continuing to use alcohol and
      psychoactive prescription medications at a higher rate than previous generations.
      The development and refinement of techniques to address these problems and
      provide early intervention services is going to be crucial to meeting the needs
      of this growing population. This chapter provides background on the extent of the
      problem, guidelines for alcohol and psychoactive medication use, and methods for
      screening and providing early interventions to improve the lives of older adults
      who misuse alcohol and/or psychoactive medications and drugs.

PMID- 22660898
TI  - The influence of state mental health perceptions and spending on an individual's
      use of mental health services.
AB  - PURPOSE: To explore the possible contextual effects of state-level mental health
      perceptions and public spending for mental health treatment on an individual's
      use of mental health services, independent of the individual's own perceptions.
      METHODS: Cross-sectional data from the 2007 Behavioral Risk Factor Surveillance
      System were used. A total of 216,514 participants from 35 states and the District
      of Columbia were included in the study. Logistic regression and multilevel
      modeling were used to estimate the effects of individual-level characteristics
      and three state-level factors-per capita spending on community mental health
      services, aggregated perceptions of the effectiveness of mental health treatment
      and the stigma of mental illness-on the individual's current use of mental health
      services. RESULTS: Adjusting for the individual's perceptions and
      characteristics, state-level perception of treatment effectiveness was positively
      associated with the use of mental health services [odds ratio (OR) for 5 %
      increase in the percentage perceiving effectiveness = 1.08; 95 % confidence
      interval (CI): 1.01, 1.16]. This association was strongest for individuals who
      experienced 1-4 days of mental distress in the past 30 days (OR = 1.17; 95 % CI
      1.06, 1.29). State-level public spending on community mental health services was
      also positively associated with an individual's use of mental health services (OR
      for a $40 increase in spending = 1.09; 95 % CI 1.01, 1.17); however, state-level
      perceptions of mental-illness stigma was not. CONCLUSIONS: Our findings suggest
      there may be contextual effects of state-level perceptions of treatment
      effectiveness and state spending on community mental health services on the use
      of mental health services.

PMID- 22660899
TI  - Image-guided percutaneous spinal biopsy.
AB  - The purpose of this article is to discuss the role of imaging in the diagnosis
      and management of spinal disorders, with particular attention to that of image
      guided percutaneous spinal biopsy. We discuss the indications, general
      principles, pre-procedural steps and specific techniques used for image-guided
      percutaneous spinal biopsy in the context of our experience and the wider
      literature. Percutaneous spinal biopsy is a safe and diagnostically accurate
      procedure when appropriately selected for further evaluation in the
      multidisciplinary team setting.

PMID- 22660900
TI  - Brassinolide enhances cold stress tolerance of fruit by regulating plasma
      membrane proteins and lipids.
AB  - How to enhance fruit tolerance to cold stress is an important biological
      interest. In this paper, we found that mango (Mangifera indica L.) fruit treated
      with 10 MUM brassinolide (BL) showed a higher tolerance to cold temperature of 5 
      degrees C. Further, we compared the changes in expression profiles of plasma
      membrane (PM) proteins and the corresponding gene expressions between BL-treated
      and control fruit. Fourteen differential proteins were positively identified by
      mass spectrometry, and were categorized into four groups, including transport,
      cellular biogenesis, defense and stress response, and unknown function. Among
      them, four proteins (remorin, abscisic stress ripening-like protein, type II SK2
      dehydrin, and temperature-induced lipocalin) and genes encoding these proteins
      were up-regulated in BL treatment under cold stress. Moreover, we found that PM
      lipids in BL-treated fruit showed lower phase transition temperature and higher
      unsaturation degree, leading to higher fluidity under low temperature. These
      findings ascertain that PM proteins and lipids are involved in BL-mediated
      responses to cold stress in mango fruit, and provide novel evidence that BL plays
      an important role in regulating cold stress tolerance in fruit.

PMID- 22660901
TI  - Dynamic changes in blood flow and oxygen consumption in the portal-drained
      viscera of growing pigs receiving acute administration of (L)-arginine.
AB  - This study tested the hypothesis that an increase in arginine concentration in
      the portal vein may affect blood flow and oxygen consumption in the portal
      drained viscera (PDV) of swine. Eight barrows (70 kg body weight) were surgically
      fitted with chronic catheters in the portal vein, ileal vein, and carotid artery.
      Thirteen days after the surgery, pigs that had been fasted for 12 h were randomly
      allocated to receive administration of either L-alanine (103 mg/kg body weight,
      isonitrogenous control) or L-arginine-HCl (61 mg/kg body weight) via the portal
      vein. Portal vein blood flow (PVBF) was measured with infusion of p-aminohippuric
      acid into the ileal vein, and blood samples were simultaneously obtained every
      0.5 h for 4 h. Compared with the control, arginine infusion increased PVBF at 30
      90 min after infusion but decreased PDV oxygen consumption at 60-150 min after
      infusion (P < 0.05). Plasma concentrations of glutamate at infusion times of 180
      240 min and of arginine at infusion times of 60-240 min in arginine-infused pigs
      were higher than those for the control group (P < 0.05). Plasma concentrations of
      insulin and glucagon at the infusion times of 30-90 min were higher and of free
      fatty acids at the infusion times of 60-120 min were lower than those for the
      control pigs (P < 0.05). These results indicate that increasing arginine
      concentration in the portal vein enhances PDV blood flow, reduces PDV oxygen
      consumption, and beneficially alters the metabolic profile in swine, an
      established animal model for studying human nutrition and metabolism.

PMID- 22660903
TI  - Programmed cell death is responsible for replaceable bud senescence in chestnut
      (Castanea mollissima BL.).
AB  - In the chestnut "replaceable bud" cultivar 'Tima zhenzhu', the auxiliary bud
      formed on the fruiting branch dies after fruiting, giving rise to a morphology
      more suitable than the wild type's for intensive cultivation and heightened
      production. Here, we show that many of the hallmarks of programmed cell death
      (PCD) occur during the senescence of the replaceable bud, including DNA
      degradation, a high ratio of PCD cells and the breakdown of cell ultrastructure.
      The time course of the senescence was followed by sampling the developing bud
      from 20 to 40 days after flowering. In cv. 'Tima zhenzhu', DNA degradation was
      detectable prior to any visible sign of bud senescence, while it did not occur in
      the wild type (cv. 'Dabanhong'). The ratio of PCD cells (as determined by flow
      cytometry) rose over the sampling period and was consistently higher in cv. 'Tima
      zhenzhu' than in cv. 'Dabanhong'. After staining the bud cell nuclei with
      propidium iodide, it was clear that both their chromatin content and overall size
      fell over the sampling period in cv. 'Tima zhenzhu' while in cv. 'Dabanhong', no
      such decrease occurred. Other characteristics of PCD were noted in cv. 'Tima
      zhenzhu''s bud cells, including chromatin condensation, tonoplast invagination
      and DNA cleavage. We conclude that the replaceable bud senescence phenomenon is
      driven by PCD. The manipulation of this trait may have potential for remodeling
      the pattern of development of the fruit-bearing branches of chestnut. KEY
      MESSAGE: This paper first reported the occurrence of programmed cell death during
      the senescence of vegetative buds in a woody species, and the results extend the
      range of knowledge of PCD.

PMID- 22660904
TI  - A comparison of different methods of temperature measurement by mothers and
      physicians in healthy newborns.
AB  - OBJECTIVE: To compare the accuracy of digital axillary thermometer (DAT), rectal
      glass mercury thermometer (RGMT) and infrared forehead skin thermometer (IFST)
      measurements made by mothers and physicians in healthy newborns. METHODS: The
      body temperature measurements of 120 healthy newborns were made on their 2nd day
      of life using DAT, RGMT and IFST, first by mothers followed by a designated
      physician. Correlation analysis was performed for the measurements obtained by
      mothers and the physician. The presence of a former child or children at home,
      the educational level of the mother and maternal age were also recorded. RESULTS:
      No correlation was observed between the measurements made by mothers and the
      physician using RGMT (R(2) = 0.096). The temperatures measured by mothers and the
      physician showed a significant correlation when a DAT and IFST were used (R(2) =
      0.923, p < 0.001; R(2) = 0.916, p < 0.001, respectively). CONCLUSIONS: Difficulty
      of use and interpretation make RGMTs less practical than DATs and IFST for use by
      mothers. Measurements with an IFST are obtained from a newborn's forehead in a
      shorter length of time compared to DATs, which makes it a more practical option.

PMID- 22660905
TI  - Radiological clue to diagnosis of Canavan disease.
AB  - Canavan disease is an autosomal recessive leukodystrophy characterized by early
      onset developmental delay, initial hypotonia progressing to hypertonia,
      macrocephaly and blindness. The authors present an infant with these clinical
      features. MRI brain shows white matter changes with characteristic involvement of
      subcortical U fibres and MR spectroscopy shows the characteristic peak of N-
      acetyl aspartate. The importance of specific clinical features and imaging in the
      diagnosis of different leukodystrophies in resource and access limited settings
      is suggested.

PMID- 22660906
TI  - Tacrolimus induced diabetic ketoacidosis in nephrotic syndrome.
AB  - Tacrolimus, a reversible calcineurin inhibitor, is known for its diabetogenic
      potential. The incidence of diabetes is less frequent among the patients of
      nephrotic syndrome in comparison to organ transplant recipients. Diabetic
      ketoacidosis (DKA) is even rarer. DKA as the first presentation of new onset
      tacrolimus induced transient type 1 diabetes despite a lower dose range and low
      trough level of the drug is being reported in a 12-y-old girl with steroid
      resistant nephrotic syndrome. 

PMID- 22660907
TI  - Unusual association of congenital hypoplasia of the depressor anguli oris muscle
      (DAOM).

PMID- 22660915
TI  - Latent inhibition in ADHD adults on and off medication: a preliminary study.
AB  - OBJECTIVE: To determine the effects of stimulant medication on performance of
      ADHD adults on a selective attention task that assesses the processing of
      irrelevant stimuli. METHOD: ADHD patients and matched controls were given two
      sessions of a two-stage visual search-latent inhibition (LI) task. In stage-1,
      they detected the location of a unique shape presented with homogeneous
      distractors. In stage- 2, target detection response time was examined as a
      function of the stage-1 experience with the target or distractor, or both,
      providing a within-subject measure of LI. In Session-1, the ADHD subjects were
      off their customary stimulant medication. In Session-2, they were on medication.
      RESULTS: Off-medicated ADHD subjects exhibited similar LI to that of controls;
      medicated ADHD subjects exhibited less LI than controls. Group differences in LI
      were mediated by RTs to the previously task-irrelevant distractor stimulus.
      CONCLUSION: The attenuated LI of the on-medication ADHD group is attributable to
      drug action that reduces attentional resources allocated to distractors.

PMID- 22660916
TI  - Task dissociation in prospective memory performance in individuals with ADHD.
AB  - OBJECTIVE: The present study investigated, for the first time, event- and time
      based prospective memory (PM) in the same sample of adults with ADHD within one
      paradigm using parallel task constraints. METHOD: A total of 25 individuals with
      ADHD and 25 matched neurotypical controls completed a computerized version of the
      Dresden Breakfast Task, which required participants to prepare breakfast
      following a set of rules and time restrictions. RESULTS: Although groups did not
      differ in event-based PM, results demonstrated a large-sized impairment in
      individuals with ADHD in time-based PM. CONCLUSION: Findings suggest a task
      specific impairment in PM functioning and are discussed in an executive control
      framework of neurocognitive functioning in ADHD.

PMID- 22660917
TI  - Reduced neural error signaling in left inferior prefrontal cortex in young adults
      with ADHD.
AB  - OBJECTIVE: The neural network involved in inhibition of inappropriate response
      tendencies shares commonalities with the error-processing network, signaling
      failure of inhibition. Most studies on error processing in ADHD have been
      conducted in children using electrophysiological methods. METHOD: Using event
      related functional magnetic resonance imaging, the authors studied 14 adults with
      ADHD and 12 group-matched healthy control participants while performing a
      modified version of a combined Eriksen Flanker-Go/NoGo-task. RESULTS: Patients
      with ADHD demonstrated significantly reduced error signaling in the left inferior
      frontal gyrus bordering the anterior insular cortex (BA 47), computed from the
      contrast of unsuccessful minus successful inhibition trials. CONCLUSION:
      Hypoactivation of the left inferior frontal cortex during error signaling might
      represent a neurofunctional marker of a crucial prerequisite for error processing
      in adults with ADHD. This possibly indicates a dysfunction of the neural system
      that operates task-set related representations and monitoring of erroneous
      performances in service of ensuing posterror processing.

PMID- 22660918
TI  - The infectious burden in atherothrombosis.
AB  - Pathogenesis of atherosclerosis involves multiple mechanisms, including
      imbalanced lipid metabolism, disturbed equilibrium of the immune response, and
      chronic inflammation of the artery wall. Several reports have shown a
      relationship between the development of atherosclerosis and the presence of
      infectious diseases, widely occurring in the general population, often chronic
      and/or asymptomatic. Beyond Chlamydia pneumoniae, a large number of infectious
      agents have been linked with an increased risk of vascular disease, with variable
      strength of supporting data: Porphyromonas gingivalis, Helicobacter pylori,
      influenza A virus, herpes virus, hepatitis C virus, cytomegalovirus, and human
      immunodeficiency virus. Infections may contribute to atherosclerosis either via
      direct infection of vascular cells or via the indirect effects of cytokines or
      acute phase proteins induced by infection at "nonvascular" sites. More recently,
      investigators reported that the aggregate burden ("infectious burden") of these
      chronic infections, rather than the effects of a single organism, might
      contribute to atherosclerosis and its thrombotic complications. However, the role
      of infection, as a proinflammatory cause of atherosclerosis, is still debated in
      the literature. This article will review available data suggesting a relationship
      between different infective pathogens and atherothrombosis, the hypothesized
      mechanisms, and the potential role for antimicrobial treatment.

PMID- 22660919
TI  - Patient safety and quality in laboratory and hemostasis testing: a renewed loop?
AB  - More than three decades ago, George Lundberg first introduced the concept of the
      brain-to-brain loop for laboratory diagnostics. According to this pioneering
      model, the first step in the loop involves the selection of laboratory tests in
      the brain of the physician caring for the patient, and the final step is the
      transmission of test results back to the ordering physician. There are several
      intermediary steps, some of which are preanalytical (e.g., identification of
      patient and blood samples, the process of blood collection, and specimen
      handling); some are analytical and relate to the actual performance of the
      test(s); whereas others are postanalytical and involve release of test results
      into the medical record and further steps such as the physician's reaction to
      laboratory information, their interpretation of these results, and subsequent
      appropriate clinical action. Hemostasis testing should also be viewed within such
      a paradigm, so that quality throughout the total testing process can be assured.
      For hemostasis testing, particular attention is required to ensure provision of
      appropriate test samples in the preanalytical phase. Nevertheless, the timeliness
      of testing and an appropriate interpretation of test results are also paramount.
      This article overviews the concept of quality testing within hemostasis as
      critical to ensuring patient safety and optimal clinical and therapeutic
      management.

PMID- 22660920
TI  - Waiting times before initiation of radiotherapy might not affect outcomes for
      patients with glioblastoma: a French retrospective analysis of patients treated
      in the era of concomitant temozolomide and radiotherapy.
AB  - Purpose of this study was to determine the effect of waiting time for
      radiotherapy on overall survival of patients with glioblastoma treated in the
      EORTC-NCIC trial at 18 centers in France. A total of 400 adult patients with
      glioblastoma who were treated between January 1, 2006 and December 31, 2006 were
      included. There were 282 patients with "minimum criteria" according to the EORTC
      NCIC trial: (i) concurrent chemotherapy with temozolomide; and (ii) age between
      18 and 70 years old. Among these patients, 229 were treated with adjuvant
      temozolomide and were classified as "maximal criteria". One-hundred and eighteen
      patients were in the "without minimal criteria" group. Waiting time from the
      first symptom (FS-RT), pathology diagnosis (P-RT), multidisciplinary meeting (MM
      RT), surgery (S-RT), and CT scan for delineation (CT-RT) until the start of
      radiotherapy were recorded. Median follow-up for all patients was 327 days.
      Overall, median FS-RT, P-RT, MM-RT, CT-RT, and S-RT times were 77, 36, 32, 12,
      and 41 days, respectively. Median, and 12 and 24-month overall survival were 409
      days, and 56.3 +/- 2.1 % and 27.6 +/- 2.6 %, respectively. Univariate analysis
      failed to reveal a difference in survival, irrespective of the delay. In
      multivariate analysis, independent favorable prognostic factors for overall
      survival were age (p <= 0.0001) and type of surgery (p = 0.0006). In this large
      series treated during the EORTC-NCIC protocol period, waiting time until
      radiotherapy did not seem to affect patient outcome.

PMID- 22660921
TI  - Resection of gliomas in the cingulate gyrus: functional outcome and survival.
AB  - Functional outcome after resection of tumors arising from the gyrus cinguli (GC),
      part of the limbic system, is not well analyzed. The purpose of this study was to
      evaluate the feasibility and functional outcome of surgical treatment for a
      series of 65 patients with gliomas involving the GC. Preoperative data, extent of
      resection, functional outcome (Karnofsky performance index, KPI, and the National
      Institute of Health Stroke Scale, NIHSS), and survival of 65 patients with
      gliomas arising from the GC were analyzed on the basis of a prospectively
      conducted database of gliomas between 06/1999 and 07/2010. Extent of resection
      (complete, subtotal, or partial) was based on early postoperative MRI. Eighty-six
      percent of the gliomas were located in the anterior part of the GC and 14 % in
      the posterior part. Fifty-five percent of the patients presented with seizures
      and 17 % with hemiparesis (mean preoperative KPI = 86 +/- 17, NIHSS = 1.4 +/-
      1.7). Histologically, the tumors were WHO Grade II in 25 %, Grade III in 26 %,
      and Grade IV in 49 %. Complete resection was achieved for 59 %, subtotal
      resection for 32%, and partial resection for 9 %. Postoperative transient
      deficits included SMA lesion (14 %) and new or worsened hemiparesis (8 %), which
      resolved within 30 days (NIHSS early postoperatively 1.7 +/- 1.4, late
      postoperatively 0.8 +/- 1.4, and after 6 months 0.6 +/- 1.4). According to
      histopathological grading, median survival was 67 months (WHO degrees II), 87
      months (WHO degrees III), and 16.5 months (WHO degrees IV), and overall survival
      was 34 months. Microsurgical resection of gliomas arising from the GC is
      feasible; gross total resection can be achieved for 90 % of gliomas arising from
      the GC with 5 % long-term morbidity.

PMID- 22660922
TI  - Astrocyte decrease in the subgenual cingulate and callosal genu in schizophrenia.
AB  - Decreases in glial cell density and in GFAP mRNA in the anterior cingulate cortex
      have been reported in schizophrenia, bipolar disorder and major depressive
      disorder. Our study examines astrocyte and oligodendrocyte density in the white
      and grey matter of the subgenual cingulate cortex, and at the midline of the genu
      of the corpus callosum, in schizophrenia, bipolar disorder, depression and normal
      control cases. Serial coronal sections were stained with H and E for anatomical
      guidance, cresyl haematoxylin for oligodendrocyte identification and GFAP
      immunohistochemistry for astrocyte identification. Oligodendrocyte and astrocyte
      density was measured using systematic anatomical distinctions and randomised
      counting methods. A significant decrease in astrocyte density was observed in
      schizophrenia compared with normal controls in the cingulate grey matter,
      cingulate white matter and the midline of the corpus callosum (p = 0.025).
      Bipolar disorder and depression cases showed no significant changes in astrocyte
      density. Oligodendrocytes did not show any changes between diagnostic groups. In
      subgenual cingulate cortex, the ratio of oligodendrocytes to astrocytes was
      decreased between the controls and the three disease groups, suggesting a
      specific glial cell type specific change in schizophrenia.

PMID- 22660923
TI  - Heart failure with a normal ejection fraction: treatments for a complex syndrome?
AB  - OPINION STATEMENT: Heart failure with a normal ejection fraction (HFNEF) now
      comprises more than 50 % of all patients with heart failure. As the population
      ages, HFNEF will continue to be a growing public health problem. Recent studies
      highlight the heterogeneity of this syndrome with regards to underlying
      pathophysiologic mechanisms. It has been recognized that multiple physiologic
      domains of cardiovascular function are abnormal in afflicted patients resulting
      in a reduced reserve capacity, which contributes in an integrated fashion to
      produce the observed phenotype. Additionally, the realization that differing
      aspects of this syndrome (eg, exercise limitations, pulmonary edema, and labile
      blood pressure) likely each have distinct physiologic causes further adds to the
      complexity. As a result of the heterogeneous nature of the pathophysiologic
      processes and comorbid illnesses in this population, there is a wide range of
      clinical outcomes. Accordingly, appreciation of the global nature of HFNEF
      ideally will better inform optimal design for future diagnostic and therapeutic
      strategies. Completed clinical trials have not resulted in any evidence-based
      treatments available for improving survival. Given the disappointing results of
      these investigations, there has been renewed interest in developing interventions
      that target underlying comorbidities and peripheral mechanisms. Additionally,
      nonpharmacologic interventions such as diet and exercise have shown promise in
      early, small clinical investigations. Finally, methods to more rationally
      subgroup patients to identify cohorts that could respond to targeted intervention
      are essential. Recognizing the success achieved in the treatment of systolic
      heart failure, or heart failure with a reduced ejection fraction (HFREF) by
      addressing neurohormonal and renal mechanisms, new therapies for HFNEF may be
      achieved by a similar shift in attention away from the heart.

PMID- 22660925
TI  - Economic growth and the human lot.

PMID- 22660924
TI  - Approach to cardiovascular disease prevention in patients with chronic kidney
      disease.
AB  - OPINION STATEMENT: Chronic kidney disease (CKD) is associated with a large burden
      of cardiovascular risk factors ultimately leading to increased cardiovascular
      events and mortality. Prevention of cardiovascular disease (CVD) in CKD involves
      early identification of individuals at high-risk of renal disease. In fact,
      substantial evidence points to a complex bidirectional relationship between CKD
      and CVD. Therefore, most interventions directed at CKD prevention should include
      multiple risk factor interventions with the goal of preventing CVD events while
      slowing progression of CKD. Clearly, prevention of CVD in CKD is a complex task
      and requires a multidisciplinary team approach, with a well-defined program,
      rational targets for each risk factor, and implementation of the most effective
      intervention strategies. Although several interventions to prevent CVD have
      proven effective in the general population and in individuals at high risk for
      CVD, a true benefit in patients with CKD remains to be demonstrated for several
      of them. A few rational targets of intervention should be optimal blood pressure
      control, reduction of proteinuria, treatment of dyslipidemia, good control of
      diabetes, smoking cessation, dietary salt restriction, achievement of normal body
      mass index, partial correction of anemia, and management of mineral metabolism
      abnormalities. Lifestyle modification and pharmacological therapy with renin
      angiotensin blockers, beta-blockers, diuretics, statins, and aspirin should be
      encouraged in the early stages of CKD.

PMID- 22660926
TI  - Alternatively activated dendritic cells regulate CD4+ T-cell polarization in
      vitro and in vivo.
AB  - Interleukin-4 is a cytokine widely known for its role in CD4(+) T cell
      polarization and its ability to alternatively activate macrophage populations. In
      contrast, the impact of IL-4 on the activation and function of dendritic cells
      (DCs) is poorly understood. We report here that DCs respond to IL-4 both in vitro
      and in vivo by expression of multiple alternative activation markers with a
      different expression pattern to that of macrophages. We further demonstrate a
      central role for DC IL-4Ralpha expression in the optimal induction of IFNgamma
      responses in vivo in both Th1 and Th2 settings, through a feedback loop in which
      IL-4 promotes DC secretion of IL-12. Finally, we reveal a central role for
      RELMalpha during T-cell priming, establishing that its expression by DCs is
      critical for optimal IL-10 and IL-13 promotion in vitro and in vivo. Together,
      these data highlight the significant impact that IL-4 and RELMalpha can have on
      DC activation and function in the context of either bacterial or helminth
      pathogens.

PMID- 22660927
TI  - Moving the O-glycoproteome from form to function.

PMID- 22660928
TI  - Modeling disease mutations by gene targeting in one-cell mouse embryos.
AB  - Gene targeting by zinc-finger nucleases in one-cell embryos provides an expedite
      mutagenesis approach in mice, rats, and rabbits. This technology has been
      recently used to create knockout and knockin mutants through the deletion or
      insertion of nucleotides. Here we apply zinc-finger nucleases in one-cell mouse
      embryos to generate disease-related mutants harboring single nucleotide or codon
      replacements. Using a gene-targeting vector or a synthetic oligodesoxynucleotide
      as template for homologous recombination, we introduced missense and silent
      mutations into the Rab38 gene, encoding a small GTPase that regulates
      intracellular vesicle trafficking. These results demonstrate the feasibility of
      seamless gene editing in one-cell embryos to create genetic disease models and
      establish synthetic oligodesoxynucleotides as a simplified mutagenesis tool.

PMID- 22660929
TI  - Stochastic branching-diffusion models for gene expression.
AB  - A challenge to both understanding and modeling biochemical networks is
      integrating the effects of diffusion and stochasticity. Here, we use the theory
      of branching processes to give exact analytical expressions for the mean and
      variance of protein numbers as a function of time and position in a spatial
      version of an established model of gene expression. We show that both the mean
      and the magnitude of fluctuations are determined by the protein's Kuramoto length
      -the typical distance a protein diffuses over its lifetime--and find that the
      covariance between local concentrations of proteins often increases if there are
      substantial bursts of synthesis during translation. Using high-throughput data,
      we estimate that the Kuramoto length of cytoplasmic proteins in budding yeast to
      be an order of magnitude larger than the cell diameter, implying that many such
      proteins should have an approximately uniform concentration. For constitutively
      expressed proteins that live substantially longer than their mRNA, we give an
      exact expression for the deviation of their local fluctuations from Poisson
      fluctuations. If the Kuramoto length of mRNA is sufficiently small, we predict
      that such local fluctuations become approximately Poisson in bacteria in much of
      the cell, unless translational bursting is exceptionally strong. Our results
      therefore demonstrate that diffusion can act to both increase and decrease the
      complexity of fluctuations in biochemical networks.

PMID- 22660930
TI  - Charge transport in molecular electronic junctions: compression of the molecular
      tunnel barrier in the strong coupling regime.
AB  - Molecular junctions are essentially modified electrodes familiar to
      electrochemists where the electrolyte is replaced by a conducting "contact." It
      is generally hypothesized that changing molecular structure will alter system
      energy levels leading to a change in the transport barrier. Here, we show the
      conductance of seven different aromatic molecules covalently bonded to carbon
      implies a modest range (< 0.5 eV) in the observed transport barrier despite
      widely different free molecule HOMO energies (> 2 eV range). These results are
      explained by considering the effect of bonding the molecule to the substrate.
      Upon bonding, electronic inductive effects modulate the energy levels of the
      system resulting in compression of the tunneling barrier. Modification of the
      molecule with donating or withdrawing groups modulate the molecular orbital
      energies and the contact energy level resulting in a leveling effect that
      compresses the tunneling barrier into a range much smaller than expected. Whereas
      the value of the tunneling barrier can be varied by using a different class of
      molecules (alkanes), using only aromatic structures results in a similar
      equilibrium value for the tunnel barrier for different structures resulting from
      partial charge transfer between the molecular layer and the substrate. Thus, the
      system does not obey the Schottky-Mott limit, and the interaction between the
      molecular layer and the substrate acts to influence the energy level alignment.
      These results indicate that the entire system must be considered to determine the
      impact of a variety of electronic factors that act to determine the tunnel
      barrier.

PMID- 22660931
TI  - Dislocation-mediated growth of bacterial cell walls.
AB  - Recent experiments have illuminated a remarkable growth mechanism of rod-shaped
      bacteria: proteins associated with cell wall extension move at constant velocity
      in circles oriented approximately along the cell circumference [Garner EC, et
      al., (2011) Science 333:222-225], [Dominguez-Escobar J, et al. (2011) Science
      333:225-228], [van Teeffelen S, et al. (2011) PNAS 108:15822-15827]. We view
      these as dislocations in the partially ordered peptidoglycan structure, activated
      by glycan strand extension machinery, and study theoretically the dynamics of
      these interacting defects on the surface of a cylinder. Generation and motion of
      these interacting defects lead to surprising effects arising from the cylindrical
      geometry, with important implications for growth. We also discuss how long range
      elastic interactions and turgor pressure affect the dynamics of the fraction of
      actively moving dislocations in the bacterial cell wall.

PMID- 22660932
TI  - Biomimetic emulsions reveal the effect of mechanical forces on cell-cell
      adhesion.
AB  - Cell-cell contacts in tissues are continuously subject to mechanical forces due
      to homeostatic pressure and active cytoskeleton dynamics. In the process of
      cellular adhesion, the molecular pathways are well characterized but the role of
      mechanics is less well understood. To isolate the role of pressure we present a
      dense packing of functionalized emulsion droplets in which surface interactions
      are tuned to mimic those of real cells. By visualizing the microstructure in 3D
      we find that a threshold compression force is necessary to overcome electrostatic
      repulsion and surface elasticity and establish protein-mediated adhesion. Varying
      the droplet interaction potential maps out a phase diagram for adhesion as a
      function of force and salt concentration. Remarkably, fitting the data with our
      theoretical model predicts binder concentrations in the adhesion areas that are
      similar to those found in real cells. Moreover, we quantify the dependence of the
      area of adhesion on the applied force and thus reveal adhesion strengthening with
      increasing external pressure even in the absence of active cellular processes.
      This biomimetic approach reveals a physical origin of pressure-sensitive adhesion
      and its strength across cell-cell junctions.

PMID- 22660933
TI  - The disproportionate high risk of HIV infection among the urban poor in sub
      Saharan Africa.
AB  - The link between HIV infection and poverty in sub-Saharan Africa (SSA) is rather
      complex and findings from previous studies remain inconsistent. While some argue
      that poverty increases vulnerability, existing empirical evidence largely support
      the view that wealthier men and women have higher prevalence of HIV. In this
      paper, we examine the association between HIV infection and urban poverty in SSA,
      paying particular attention to differences in risk factors of HIV infection
      between the urban poor and non-poor. The study is based on secondary analysis of
      data from the Demographic and Health Surveys from 20 countries in SSA, conducted
      during 2003-2008. We apply multilevel logistic regression models, allowing the
      urban poverty risk factor to vary across countries to establish the extent to
      which the observed patterns are generalizable across countries in the SSA region.
      The results reveal that the urban poor in SSA have significantly higher odds of
      HIV infection than their urban non-poor counterparts, despite poverty being
      associated with a significantly lower risk among rural residents. Furthermore,
      the gender disparity in HIV infection (i.e. the disproportionate higher risk
      among women) is amplified among the urban poor. The paper confirms that the
      public health consequence of urban poverty that has been well documented in
      previous studies with respect to maternal and child health outcomes does apply to
      the risk of HIV infection. The positive association between household wealth and
      HIV prevalence observed in previous studies largely reflects the situation in the
      rural areas where the majority of the SSA populations reside.

PMID- 22660934
TI  - HIV and H2O: tracing the connections between gender, water and HIV.
AB  - The health consequences for HIV-affected families of insufficient access to safe
      water and sanitation are particularly dire: inadequate access complicates
      medication adherence and increases vulnerability to opportunistic infections for
      persons living with HIV. The gendered nature of water collection and HIV care-
      with women disproportionately bearing the burden in both areas--presents an
      unrealized opportunity to improve HIV outcomes through investments in
      water/sanitation. We synthesize the literature on HIV and water/sanitation to
      develop a conceptual model that maps the connections between women's double
      burden of resource collection and HIV care. Drawing on theories of gender and
      systems science, we posit that there are multiple paths through which improved
      water/sanitation could improve HIV-related outcomes. Our findings suggest that
      the positive synergies of investing in water/sanitation in high HIV prevalence
      communities that are also expanding access to ART would be significant, with
      health multiplying effects that impact women and entire communities.

PMID- 22660935
TI  - Are joint torque models limited by an assumption of monoarticularity?
AB  - This study determines whether maximal voluntary ankle plantar flexor torque could
      be more accurately represented using a torque generator that is a function of
      both knee and ankle kinematics. Isovelocity and isometric ankle plantar flexor
      torques were measured on a single participant for knee joint angles of 111
      degrees  to 169 degrees  (approximately full extension) using a Contrex MJ
      dynamometer. Maximal voluntary torque was represented by a 19-parameter two-joint
      function of ankle and knee joint angles and angular velocities with the
      parameters determined by minimizing a weighted root mean square difference
      between measured torques and the two-joint function. The weighted root mean
      square difference between the two-joint function and the measured torques was 10
      N-m or 3% of maximum torque. The two-joint function was a more accurate
      representation of maximal voluntary ankle plantar flexor torques than an existing
      single-joint function where differences of 19% of maximum torque were found. It
      is concluded that when the knee is flexed by more than 40 degrees , a two-joint
      representation is necessary.

PMID- 22660937
TI  - [The editorial - a mixture between aperitif and digestif].

PMID- 22660936
TI  - MicroRNAs in renal development.
AB  - The discovery of microRNAs (miRNAs) as novel regulators of gene expression has
      led to a marked change in how gene regulation is viewed, with important
      implications for development and disease. MiRNAs are endogenous, small, noncoding
      RNAs that largely repress their target mRNAs post-transcriptionally. The
      regulation of gene expression by miRNAs represents an evolutionarily conserved
      mechanism that is broadly applicable to most biological processes. Recent studies
      have begun to define the role of miRNAs in different cell lineages during kidney
      development, and to implicate specific miRNAs in developmental and
      pathophysiological processes in the kidney. This review will focus on novel
      insights into the role(s) of miRNAs in kidney development, and discuss the
      implications for pediatric renal disease.

PMID- 22660939
TI  - New Kaiser resources address behavioral health financing and access options under
      health reform.

PMID- 22660941
TI  - Theoretical study on novel nitrogen-rich energetic compounds of bis(amino)
      azobis(azoles) with tetrazene unit.
AB  - Six stereoisomers of 5,5'-bis(amino)-1,1'-azobis(tetrazoles) and 30 other
      structures, including all possible bis(amino)-azobis(azoles) with an N-N=N-N
      unit, were designed. The molecular geometries were fully optimized at the DFT
      B3LYP level with the 6-31++g (d, p) basis set. From the absence of any imaginary
      frequency in the infrared vibration frequency spectrum, it is predicted that all
      these studied structures may exist in stable forms. The results of the total
      energies of the stereoisomers of 5,5'-bis(amino)-1,1'-azobis(tetrazoles) indicate
      that the two symmetric trans-form structures are more likely to exist than the
      other four. The pyrolysis process, chemical stability and molecular electrostatic
      potential were studied via the investigation of their electronic structure. Heats
      of formation (HOFs) were calculated using the atomization energy method based on
      the results of the harmonic vibration frequencies, and a linear relationship was
      found between the HOF and nitrogen chain or nitrogen content. Densities of the
      title compounds were predicted with the Monte Carlo method. Finally, according to
      the results of the calculated HOFs and densities, the explosive parameters of
      these compounds were calculated using the Kamlet-Jacobs formula. 5,5'-Bis(amino)
      1,1'-azobis(tetrazoles) and its isomer 5,5'-bis(amino)-2,2'-azobis(tetrazoles)
      may have potential for use as energetic compounds.

PMID- 22660942
TI  - Does the copolymer poly(vinylidene cyanide-tricyanoethylene) possess
      piezoelectricity?
AB  - The geometry, energy, internal rotation barrier, dipole moment, and molecular
      polarizability of the alpha- and beta-chain models of poly(vinylidene cyanide
      tricyanoethylene) [P(VDCN-TrCN)] were studied with density functional theory at
      the B3PW91/6-31G(d) level. The effects of the chain length and the TrCN content
      on the copolymer chain stability, the chain conformation, and the electrical
      properties of P(VDCN-TrCN) were examined and compared with those of
      poly(vinylidene fluoride-trifluoroethylene) and PVDCN to gauge whether P(VDCN
      TrCN) would be expected to possess substantial piezoelectricity. The results of
      this study showed that the stability of the beta conformation increases and the
      energy difference per monomer unit between the beta- and alpha-chains decreases
      with increasing TrCN. However, introducing TrCN into VDCN will not significantly
      enhance the radius of curvature of the P(VDCN-TrCN) chains. The average dipole
      moment per monomer unit in the beta-chain is affected by the chain curvature and
      the TrCN content. The amount of piezoelectricity present in P(VDCN-TrCN) is
      slightly smaller than that in PVDCN, and is less than that in poly(vinylidene
      fluoride-trifluoroethylene).

PMID- 22660943
TI  - Carbenic vs. ionic mechanistic pathway in reaction of cyclohexanone with
      bromoform.
AB  - The extensive computation study was done to elucidate the mechanism of formation
      dibromoepoxide from cyclohexanone and bromoform. In this reaction, the formation
      of dihaloepoxide 2 is postulated as a key step that determines the distribution
      and stereochemistry of products. Two mechanistic paths of reaction were
      investigated: the addition of dibromocarbene to carbonyl group of ketone, and the
      addition of tribromomethyl carbanion to the same (C=O) group. The mechanisms for
      the addition reactions of dibromocarbenes and tribromomethyl carbanions with
      cyclohexanone have been investigated using ab initio HF/6-311++G** and MP2/6
      311+G* level of theory. Solvent effects on these reactions have been explored by
      calculations which included a continuum polarizable conductor model (CPCM) for
      the solvent (H2O). The calculations showed that both mechanisms are possible and
      are exothermic, but have markedly different activation energies.

PMID- 22660945
TI  - Brain regions associated with psychological pain: implications for a neural
      network and its relationship to physical pain.
AB  - Research on brain areas involved in experiencing emotion and physical pain is
      abundant; however, psychological pain has received little attention in studies of
      the brain. The purpose of this systematic review was to provide an overview of
      studies on brain function related to psychological pain. The review was limited
      to studies in which participants experienced actual psychological pain or
      recalled a significant autobiographical event that may be assumed to have
      involved psychological pain. Based on results of the studies (N = 18), a
      tentative neural network for psychological pain is proposed that includes the
      thalamus, anterior and posterior cingulate cortex, the prefrontal cortex,
      cerebellum, and parahippocampal gyrus. Results indicated that grief may be a more
      accurate exemplar of psychological pain than recalled sadness, with indications
      of greater arousal during psychological pain. The proposed neural network for
      psychological pain overlaps to some extent with brain regions involved in
      physical pain, but results suggest a markedly reduced role for the insula,
      caudate, and putamen during psychological pain. Psychological pain is well known
      for its association with depression and as a precursor of suicidal behavior.
      Thus, identification of brain areas involved in psychological pain may help guide
      development of interventions to decrease mortality and morbidity.

PMID- 22660944
TI  - Molecular modeling and active site analysis of SdiA homolog, a putative quorum
      sensor for Salmonella typhimurium pathogenecity reveals specific binding patterns
      of AHL transcriptional regulators.
AB  - Salmonella typhimurium is a Gram-negative bacterium responsible for human
      diseases including gastroenteritis and typhoid fever and its quorum sensing
      system is currently being intensively researched. Molecular modeling and binding
      site analysis of SdiA homolog, a putative quorum sensor of the LuxR family and
      responsible for S. typhimurium pathogenecity revealed a high structural homology
      of their active site with three other LuxR family proteins LasR from Pseudomonas
      aeruginosa, TraR from Agrobacterium tumifaciens and CviR from Chromobacterium
      violaceum. The results show that all the LuxR family proteins harbor three
      conserved amino acids Tryptophan (W67) and Aspartic acid (D80) for formation of
      hydrogen bridges and Tyrosine (Y71) for the hydrophobic interactions
      (corresponding to their position in S. typhimurium SdiA) with acyl homoserine
      lactones (AHL)-dependent transcriptional regulators. However, in addition to the
      above conserved residues, Arginine (R60) also plays an important role in S.
      typhimurium SdiA binding with its AHL auto inducers and the complex is found to
      be stronger because of the interactions between nitrogen atoms of Arginine with
      the carbonyl oxygen in the lactone ring of AHL. The specific binding patterns
      would be helpful in guiding both enzymatic studies as well as design of specific
      inhibitors to overcome S. typhimurium pathogenecity.

PMID- 22660947
TI  - On the emergence of the subject.
AB  - The paper retraces the elaboration of a model that accounts for the emergence of
      subjectivity-the possibility to distance self from others and oneself-if we
      consider people as always taken in social and cultural streams of meaning and
      tensions. It builds a model considering first, human experience as possible when
      a person takes distance from the here-and-now. Second, it suggests considering
      two general semiotic streams that feed in, or support, that distancing-social and
      cultural discourses, and personal experience. Third, a knitting model suggests
      the constant creation of personal patters out of these two streams. Fourth, a
      dynamic, star-like model is proposed to account for the actual and constant
      emergence of subjectivity out of such social and cultural configurations. The
      model is constituted by a 2, 3 or N-number of eight-shaped crossing loops,
      resulting in a star-like model situated in a 3 dimensional space. The proposition
      is to analyze a person in a specific situation: the attractors enabling these
      loops, or end-points of the star, are the relevant social and cultural elements:
      others with whom he or she interacts, specific bodies of shared knowledge, social
      representations, cultural elements and tools, and so on. In each situation, the
      relative strength of these elements, or the tension they generate, are negotiated
      by the person; the unique ways of dealing with that situation and inviting
      solutions can thus be seen as the emergent subjectivity. The model is explored to
      account for developmental dynamics at various scales in the lifecourse. Finally,
      the pragmatic interest of a model emphasizing complex configurations, not simple
      causalities, is recalled.

PMID- 22660946
TI  - Population genetic structure of the melon fly, Bactrocera cucurbitae (Coquillett)
      (Diptera: Tephritidae) based on mitochondrial cytochrome oxidase (COI) gene
      sequences.
AB  - Population genetic structure of melon fly analysed with mitochondrial cytochrome
      oxidase I gene suggested that melon fly populations across the globe is
      homogeneous with non-significant variation of 0.000-0.003 base substitutions per
      site. Test isolates representing various geographic situations across the world
      were placed in 26 mitochondrial haplotypes based on variations associated with a
      maximum of three mutational steps and the predominant haplotype i.e. H1 was
      present in all melon fly populations except Hawaiian population. Evolution of
      mtCOI gene suggested that the fly could have originated some 0.4 million years
      ago. The present study also indicated that the B. cucurbitae population expansion
      is an event of post Pleistocene warm climatic conditions with small number of
      founder population. The invasion of B. cucurbitae in Hawaii was associated with
      the large population size and the global presence of the fly is associated with
      human mediated dispersal. The very low genetic variation suggested that the fly
      management might be possible by large scale sterile insect techniques programme.

PMID- 22660949
TI  - Management of patients undergoing rhinoplasty while receiving anticoagulant
      therapy.
AB  - A proper bloodless field and coagulation profile represent essential elements for
      performing a safe, effective, and fast rhinoplasty. However, some particular
      conditions among patients with a high thromboembolic risk for congenital
      thrombophilia require antithrombotic prophylaxis using low-molecular-weight
      heparin. To date, the literature contains no particular indication for the
      management of patients undergoing rhinoseptoplasty while receiving anticoagulant
      therapy. The authors report their experience managing a 36-year-old man who
      underwent aesthetic rhinoseptoplasty while at the same time carrying a
      heterozygous mutation (G20210A) of prothrombin and a homozygous mutation of
      methylenetetrahydrofolate reductase (C677T). Special attention must be paid to
      balancing the prevention and reduction of thrombotic risk for excessive
      anticoagulation, which would make surgery unsafe and difficult to perform. LEVEL
      OF EVIDENCE IV: This journal requires that authors assign a level of evidence to
      each article.

PMID- 22660950
TI  - Lipoma with bone and cartilage components in the left axilla of a middle-aged
      woman.
AB  - Lipoma is the most common type of benign soft tissue tumor. However, lipoma
      containing bone or cartilage is very rare, especially a tumor containing both of
      these components. We encountered a 59-year-old woman who had a benign lipoma of
      the infraspinatus muscle that contained both osseous and chondral components.
      Histopathological examination revealed the presence of chondral and osseous
      elements mixed with mature adipose tissue. To the best of our knowledge, there
      has never been a report of benign lipoma containing osteochondral tissue at this
      location. Therefore, we report the first case of an axillary lipoma with bone and
      cartilage components. LEVEL OF EVIDENCE V: This journal requires that authors
      assign a level of evidence to each article.

PMID- 22660951
TI  - Shewanella litorisediminis sp. nov., a gammaproteobacterium isolated from a tidal
      flat sediment.
AB  - A Gram-negative, facultatively anaerobic, non-motile and rod-shaped bacterial
      strain, designated SMK1-12(T), was isolated from a tidal flat sediment on the
      western coast of Korea. Phylogenetic analyses based on 16S rRNA  and gyrB gene
      sequences showed that strain SMK1-12(T) belonged to the genus Shewanella,
      clustering with the type strain of Shewanella amazonensis. Strain SMK1-12(T)
      exhibited the highest 16S rRNA gene sequence similarity value (97.0 %) and the
      highest gyrB sequence similarity value (87.8 %) to S. amazonensis SB2B(T),
      respectively. Strain SMK1-12(T) contained simultaneously both menaquinones and
      ubiquinones; the predominant menaquinone was MK-7 and the predominant ubiquinones
      were Q-7 and Q-8. The major fatty acids (>10 % of the total fatty acids) detected
      in strain SMK1-12(T) were the MIDI system summed feature 3 (iso-C(15:0) 2-OH
      and/or C(16:1) omega7c), iso-C(15:0), C(17:1) omega8c and C(16:0). The DNA G+C
      content of strain SMK1-12(T) was 58.0 mol% and its mean DNA-DNA relatedness value
      with S. amazonensis ATCC 700329(T) was 15 +/- 4.6 %. Differential phenotypic
      properties, together with the phylogenetic and genetic distinctiveness, revealed
      that strain SMK1-12(T) is distinguishable from recognized Shewanella species. On
      the basis of the data presented, strain SMK1-12(T) is considered to represent a
      novel Shewanella species, for which the name Shewanella litorisediminis sp. nov.
      is proposed. The type strain is SMK1-12(T) (=KCTC 23961(T) = CCUG 62411(T)).

PMID- 22660952
TI  - Staphylococcus haemolyticus strains target mitochondria and induce caspase
      dependent apoptosis of macrophages.
AB  - The aim of this study was to investigate the interaction of Staphylococcus
      haemolyticus strains with a macrophage cell line. Infection with the strains
      resulted in macrophage injury. All strains exhibited cytotoxic effects towards
      J774 cells. Moreover, the bacteria triggered apoptosis of the cells. The lowest
      apoptotic index did not exceed 21 %, whereas the highest reached 70 % at 24 h and
      85 % at 48 h after infection. Incubation with the bacteria caused loss of
      mitochondrial membrane potential (DeltaPsim) in macrophages. The pro-apoptotic
      activity of the strains was blocked by a pan-caspase inhibitor z-VAD-fmk,
      indicating the involvement of caspases in the bacteria-mediated cell death. We
      observed that the induction of macrophage apoptosis could constitute an important
      mechanism of pathogenesis by which S. haemolyticus strains evade host immune
      defences and cause disease.

PMID- 22660953
TI  - The ABA signal transduction mechanism in commercial crops: learning from
      Arabidopsis.
AB  - The phytohormone abscisic acid (ABA) affects a wide range of stages of plant
      development as well as the plant's response to biotic and abiotic stresses.
      Manipulation of ABA signaling in commercial crops holds promising potential for
      improving crop yields. Several decades of research have been invested in attempts
      to identify the first components of the ABA signaling cascade. It was only in
      2009, that two independent groups identified the PYR/PYL/RCAR protein family as
      the plant ABA receptor. This finding was followed by a surge of studies on ABA
      signal transduction, many of them using Arabidopsis as their model. The ABA
      signaling cascade was found to consist of a double-negative regulatory mechanism
      assembled from three protein families. These include the ABA receptors, the PP2C
      family of inhibitors, and the kinase family, SnRK2. It was found that ABA-bound
      PYR/RCARs inhibit PP2C activity, and that PP2Cs inactivate SnRK2s. Researchers
      today are examining how the elucidation of the ABA signaling cascade in
      Arabidopsis can be applied to improvements in commercial agriculture. In this
      article, we have attempted to review recent studies which address this issue. In
      it, we discuss various approaches useful in identifying the genetic and protein
      components involved. Finally, we suggest possible commercial applications of
      genetic manipulation of ABA signaling to improve crop yields.

PMID- 22660954
TI  - GLCCI1 single nucleotide polymorphisms in pediatric nephrotic syndrome.
AB  - BACKGROUND: Empiric steroid therapy is the first-line therapy for pediatric
      nephrotic syndrome, but treatment response is variable. There are few predictors
      of steroid-responsiveness, although evidence for genetic factors does exist.
      Single nucleotide polymorphisms (SNPs) have been recently identified in the
      promoter region of glucocorticoid-induced transcript 1 gene (GLCCI1) which affect
      steroid-responsiveness in asthmatic patients. Independently, GLCCI1 was
      identified as a podocyte protein, the loss of which disrupts the function of the
      glomerular filtration barrier. We therefore examined whether SNPs associated with
      the steroid-responsive expression of GLCCI1 might predict steroid-responsiveness
      in nephrotic syndrome. CASE-DIAGNOSIS/TREATMENT: A cohort of 211 pediatric
      patients with nephrotic syndrome and 102 controls were genotyped; among the
      cases, 117 were initial steroid responders, while 94 did not respond to oral
      steroids. No statistically significant differences were noted among the groups,
      although there was a trend based on the comparison of the small subgroups of
      steroid-responsive and non-responsive patients with biopsy-proven minimal change
      disease. CONCLUSIONS: While larger cohorts are needed to ascertain the
      possibility of a small effect of GLCCI1 SNPs on the steroid-responsiveness of
      nephrotic syndrome, the GLCCI1 SNPs associated with steroid-responsiveness in
      asthmatic patients are unlikely to have a clinically actionable impact in
      pediatric nephrotic syndrome.

PMID- 22660955
TI  - Vitamin D status of children receiving chronic dialysis.
AB  - BACKGROUND: Patients receiving chronic dialysis therapy are presumed to be at
      risk for 25(OH) D(3) deficiency, but little information is available on its
      prevalence, manifestations of deficiency, and the impact of ergocalciferol
      supplementation. METHODS: A single-center, retrospective study of 51 prevalent
      pediatric patients on hemodialysis or peritoneal dialysis was conducted to
      address these issues. RESULTS: Forty of 51 (78.4 %) patients had low (<30 ng/ml)
      25(OH) D(3) levels. Of these, 2 % had values < 5 ng/ml, 41.2 % 5-15 ng/ml, and
      35.3 % 16-30 ng/ml. Age >12 years, non-Caucasian race and > 12-month duration of
      dialysis were significantly associated with low 25(OH) D(3) levels (p = 0.006, p
      = 0.05, and p = 0.04, respectively). Twenty-three of the 40 patients deficient in
      25(OH) D(3) received repletion therapy with ergocalciferol and had a follow-up
      level at an average of 2 months following completion of a single course of
      therapy; 14 (60 %) of the levels were normal. Mean baseline intact parathyroid
      hormone (iPTH) for patients with 25(OH) D(3) levels <= 30 was 478.68 +/- 474.01
      pg/ml and treatment with ergocalciferol was not associated with a significant
      decrease in the mean iPTH value (p = 0.45). CONCLUSIONS: We conclude that low
      25(OH) D(3) levels are common in pediatric patients receiving dialysis and
      require attention in accordance with current practice guidelines.

PMID- 22660957
TI  - Can dialysis modality influence cardiovascular outcome?

PMID- 22660956
TI  - Discordant phenotype in monozygotic twins with renal coloboma syndrome and a PAX2
      mutation.
AB  - BACKGROUND: Renal coloboma syndrome (RCS) is a highly variable syndrome
      characterized by renal and ocular abnormalities. It is associated in about 50 %
      of cases with mutations of PAX2, a gene encoding a transcription factor required
      during development. CASE-DIAGNOSIS/TREATMENT: The case study involves two
      monozygotic twin sisters with RCS showing highly discordant phenotypes. Twin 1
      was antenatally diagnosed with multiple cysts in the right kidney. She had
      complicated vacuum-assisted delivery with acute renal failure. She developed
      proteinuria at age 4 years, followed by a progressive rise in serum creatinine
      requiring renal replacement therapy at age 22. No ocular abnormalities have been
      detected. Twin 2 experienced rapidly reversible acute renal failure without renal
      morphological abnormalities at birth. At age 2 years, complete visual acuity loss
      of the left eye secondary to an optic disc coloboma was diagnosed. No significant
      events occurred until the age of 20, when clinical proteinuria was detected.
      Proteinuria remission was obtained by multidrug treatment. In both patients, a
      novel de novo mutation of PAX2 was detected, which leads to the substitution of a
      highly conserved cysteine (p.C52Y). CONCLUSIONS: The patients described provide
      an extreme example of clinical variability in RCS. The role of environmental,
      genetic, and epigenetic factors is discussed.

PMID- 22660958
TI  - Growth hormone improves growth in pediatric renal transplant recipients--a
      systemic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Growth hormone had been applied to treat pediatric renal allograft
      recipients with growth retardation. In this systemic review and meta-analysis, we
      assess the efficiency and safety of growth hormone use in post-renal transplant
      children. METHODS: A literature search revealed five prospective randomized
      controlled trials assessing this therapy, with a total of 401 patients. The
      outcomes, including the baseline height standard deviation score (HSDS), HSDS
      after a 1-year therapy, delta height standard deviation score (?HSDS), allograft
      rejection rates and changes in the glomerular filtration rates (GFR) were
      analyzed. RESULTS: Pooled data of the five studies showed that 1 year after the
      randomized controlled trials, the experimental group receiving growth hormone had
      a significantly higher growth velocity than the control group, with a mean HSDS
      difference of 0.68 [95 % confidence interval (CI) 0.25-1.11, P = 0.002] between
      the two groups. The mean difference in the ?HSDS between the treated and control
      group was 0.52 (95 % CI 0.37-0.68, P < 0.00001). The rejection episode rates were
      35/205 and 19/185, respectively (number of patients with rejection/ total number
      of patients) (risk ratio 1.56, 95 % CI 0.97-2.53, P = 0.07), and the mean
      difference in the ?GFR was 3.27 ml/min per 1.73 m(2) (95 % CI -3.54-10.09, P =
      0.35), which was not statistically significant. CONCLUSIONS: Based on these
      studies, we suggest that the application of growth hormone is an effective
      treatment to promote the growth velocity of children after kidney
      transplantation. However, the safety of this treatment needs further evaluation.

PMID- 22660959
TI  - Evaluation of two methods of the jump float serve in volleyball.
AB  - A novel jump-focused (JF) technique of the jump float serve was compared with the
      conventionally used contact-focused (CF) method. Seven elite male (height: 195 +/
      6 cm) and two elite female (height: 181 and 182 cm) volleyball players were
      videoed at 60 Hz performing both techniques. Horizontal and vertical ball contact
      coordinates, pre- and postcontact ball velocities, and initial projection angles
      were determined. The JF technique resulted in a significantly higher mean contact
      height, t(8) = 4.12, p = .006, d = 0.72, initial serve speed, t(8) = 4.71, p =
      .006, d = 2.03, and significantly flatter initial projection angle, t(8) = 2.53,
      p = .036, d = 0.63, relative to the CF technique. The precontact vertical ball
      velocity was also significantly higher, t(8) = 8.04, p = .004, d = 2.86. The
      higher precontact vertical ball velocity suggests it is more difficult to make
      accurate contact with the ball during the JF technique. However, this method
      promotes a more favorable ball trajectory and a greater initial serve speed. When
      combining the random lateral movement patterns inherent in any float serve, with
      the reduced flight time associated with the JF technique, a more challenging
      passing scenario can be presented to the defensive team in comparison with the
      current CF technique.

PMID- 22660960
TI  - Seizure treatment in transplant patients.
AB  - OPINION STATEMENT: Solid organ transplantation is frequently complicated by a
      spectrum of seizure types, including single partial-onset or generalized tonic
      clonic seizures, acute repetitive seizures or status epilepticus, and sometimes
      the evolution of symptomatic epilepsy. There is currently no specific evidence
      involving the transplant patient population to guide the selection,
      administration, or duration of antiepileptic drug (AED) therapy, so familiarity
      with clinical AED pharmacology and application of sound judgment are necessary
      for successful patient outcomes. An initial detailed search for symptomatic
      seizure etiologies, including metabolic, infectious, cerebrovascular, and
      calcineurin inhibitor treatment-related neurotoxic complications such as
      posterior reversible encephalopathy syndrome (PRES), is imperative, as underlying
      central nervous system disorders may impose additional serious risks to cerebral
      or general health if not promptly detected and appropriately treated. The
      mainstay for post-transplant seizure management is AED therapy directed toward
      the suspected seizure type. Unfavorable drug interactions could place the
      transplanted organ at risk, so choosing an AED with limited interaction potential
      is also crucial. When the transplanted organ is dysfunctional or vulnerable to
      rejection, AEDs without substantial hepatic metabolism are favored in post-liver
      transplant patients, whereas after renal transplantation, AEDs with predominantly
      renal elimination may require dosage adjustment to prevent adverse effects.
      Levetiracetam, gabapentin, pregabalin, and lacosamide are drugs of choice for
      treatment of partial-onset seizures in post-transplant patients given their
      efficacy spectrum, generally excellent tolerability, and lack of drug interaction
      potential. Levetiracetam is the drug of choice for primary generalized seizures
      in post-transplant patients. When intravenous drugs are necessary for acute
      seizure management, benzodiazepines and fosphenytoin are the traditional and best
      evidence-based options, although intravenous levetiracetam, valproate, and
      lacosamide are emerging options. Availability of several newer AEDs has greatly
      expanded the therapeutic armamentarium for safe and efficacious treatment of post
      transplant seizures, but future prospective clinical trials and pharmacokinetic
      studies within this specific patient population are needed.

PMID- 22660961
TI  - Population-based survival data for brain tumors in Korea.
AB  - Primary brain tumors are relatively uncommon but particularly lethal cancers.
      Although survival is useful for monitoring the effects of early cancer detection
      and treatment, there are few population-based estimates of survival for subjects
      with brain tumors, especially in Asian countries. Using the Korea National Cancer
      Incidence Database, 4,721 newly diagnosed cases of histologically confirmed
      malignant primary brain tumors from 1999 to 2004 were analyzed for observed
      survival. For trend analyses of glioblastomas, we included 2,751 glioblastoma
      cases diagnosed between 1999 and 2007. We compared survival by age group and
      histological type by use of the Kaplan-Meier method. For all ages and all brain
      tumor types in Korea, five-year survival was 37.5 %. For each histological type
      of brain tumor survival of pediatric and younger adult populations was much
      better than that of older adults. Five-year survival for glioblastoma,
      astrocytoma, anaplastic astrocytoma, and oligodendroglioma was 8.9, 51.6, 25.2,
      and 73.5 %, respectively. Two-year survival for glioblastoma increased from 18.6
      % for cases diagnosed in 1999-2001 to 21.3 % for cases diagnosed in 2002-2004 and
      to 24.7 % for cases diagnosed in 2005-2007. These results may help clinicians and
      patients to assess long-term prognoses for brain tumors, and the data presented
      here could serve as master control data set for single-arm clinical trials,
      especially in Asian populations.

PMID- 22660962
TI  - Prospective comparison of noninvasive, bedside ultrasound methods for assessing
      central venous pressure.
AB  - PURPOSE: To prospectively evaluate the accuracy of noninvasive central venous
      pressure (CVP) assessment by compression ultrasound of a forearm vein (CUS),
      inferior vena cava (IVC-C) and internal jugular vein collapsibility (IJV-C)
      compared to invasive CVP measurement (invCVP) as the gold standard. MATERIALS AND
      METHODS: CUS, IVC-C and IJV-C were performed in a random sequence in 81
      consecutive intensive care patients with simultaneous invCVP monitoring.
      Examiners were blinded to invCVP and previous examinations. RESULTS: Median
      invCVP was 12.0 mmHg (range 1 - 23). CUS, IVC-C and IJV-C could be obtained in 89
      %, 95 % and 100 % of cases, respectively, within a median time of 188 sec [IQR
      125; 270], 133 sec [IQR 100; 211] and 60 sec [IQR 50; 109], respectively. The
      Spearman correlation coefficient between invCVP and CUS, IVC-C, and IJV-C was
      0.485 95 %-CI [0.25; 0.65], -0.186 [-0.42; 0.07], and -0.408 [-0.59; -0.18],
      respectively. The median absolute difference between CUS and invCVP was 3 mmHg
      [IQR 2; 6.75]. CVP was categorized as low (< 7 mmHg; collapsibility > 0.6),
      normal (7 - 12 mmHg; collapsibility 0.6 - 0.2) and high (> 12 mmHg;
      collapsibility < 0.2) as prespecified. The proportions of identical CVP
      classifications compared to invCVP were 61.4% 95%-CI [49.3%; 72.4%] with CUS,
      48.7% [37.4%; 60%] with IVC-C and 51.3% [40.3%; 62.3%] with IJV-C (p > 0.10 for
      all pair-wise comparisons). CONCLUSION: The overall ability of CUS, IVC-C and IJV
      C to assess invCVP was only moderate. CUS seems to be the preferable method if
      absolute CVP values are needed. IJV-C seems to be the fastest and most easily
      acquirable method, and thus may be especially valuable in emergency rooms.

PMID- 22660963
TI  - Are amino groups advantageous to insensitive high explosives (IHEs)?
AB  - There is usually a contradiction between increasing energy densities and reducing
      sensitivities of explosives. The explosives with both high energy densities and
      low sensitivities, or the so-called insensitive high explosives (IHEs), are
      desirable in most cases. It seems from applied explosives that amino groups are
      advantageous to IHE but the amount of amino groups contained IHEs is very
      limited. To make this clear, we present systemic examinations of the effects on
      the two properties stressed in IHEs after introducing amino groups to different
      molecular skeletons. As a result, the amino groups on resonant sites to nitro
      groups in conjugated systems can improve distinctly sensitivities and change
      energy densities in terms of oxygen balance; while the amino groups in
      unconjugated systems can hardly increase energy densities and usually cause
      increased sensitivities. It agrees well with a fact that almost all the molecules
      of applied amino group contained explosives possess conjugated skeletons. We
      therefore confirm that if amino groups are introduced resonantly to a nitro group
      in a conjugated system and the introduction improves OB, they are advantageous to
      IHEs.

PMID- 22660964
TI  - The effect of posterior tibial slope on knee flexion in posterior-stabilized
      total knee arthroplasty.
AB  - PURPOSE: To evaluate and quantify the effect of the tibial slope on the
      postoperative maximal knee flexion and stability in the posterior-stabilized
      total knee arthroplasty (TKA). METHODS: Fifty-six patients (65 knees) who had
      undergone TKA with the posterior-stabilized prostheses were divided into the
      following 3 groups according to the measured tibial slopes: Group 1: <=4 degrees
      , Group 2: 4 degrees -7 degrees  and Group 3: >7 degrees . The preoperative range
      of the motion, the change in the posterior condylar offset, the elevation of the
      joint line, the postoperative tibiofemoral angle and the preoperative and
      postoperative Hospital for Special Surgery (HSS) scores were recorded. The tibial
      anteroposterior translation was measured using the Kneelax 3 Arthrometer at both
      the 30 degrees  and the 90 degrees  flexion angles. RESULTS: The mean values of
      the postoperative maximal knee flexion were 101 degrees  (SD 5), 106 degrees  (SD
      5) and 113 degrees  (SD 9) in Groups 1, 2 and 3, respectively. A significant
      difference was found in the postoperative maximal flexion between the 3 groups (P
      < 0.001). However, no significant differences were found between the 3 groups in
      the postoperative HSS scores, the changes in the posterior condylar offset, the
      elevation of the joint line or the tibial anteroposterior translation at either
      the 30 degrees  or the 90 degrees  flexion angles. A 1 degrees  increase in the
      tibial slope resulted in a 1.8 degrees  flexion increment (r = 1.8, R (2) =
      0.463, P < 0.001). CONCLUSION: An increase in the posterior tibial slope can
      significantly increase the postoperative maximal knee flexion. The tibial slope
      with an appropriate flexion and extension gap balance during the operation does
      not affect the joint stability.

PMID- 22660965
TI  - Specific interaction of the envelope glycoproteins E1 and E2 with liver heparan
      sulfate involved in the tissue tropismatic infection by hepatitis C virus.
AB  - The first step in the process of infections by the hepatitis C virus (HCV) is
      attachment to the host cell, which is assumed to be mediated by interaction of
      the envelope glycoproteins E1 and E2 with cell surface glycosaminoglycans. In
      this study, a variety of glycosaminoglycans, heparan sulfate (HS) from various
      bovine tissues as well as chondroitin sulfate (CS)/dermatan sulfate from bovine
      liver, were used to examine the direct interaction with recombinant E1 and E2
      proteins. Intriguingly, among HS preparations from various bovine tissues, only
      liver HS strongly bound to both E1 and E2. Since HS from liver, which is the
      target tissue of HCV, contains highly sulfated structures compared to HS from
      other tissues, the present results suggest that HS-proteoglycan on the liver cell
      surface appears to be one of the molecules that define the liver-specific tissue
      tropism of HCV infection. The interaction assay with chemically modified heparin
      derivatives provided evidence that the binding of the viral proteins to
      heparin/HS is not only mediated by simple ionic interactions, but that the 6-O
      sulfation and N-sulfation are important. Heparin oligosaccharides equal to or
      larger than 10-mer were required to inhibit the binding. Notably, a highly
      sulfated CS-E preparation from squid cartilage also strongly interacted with both
      viral proteins and inhibited the entry of pseudotype HCV into the target cells,
      suggesting that the highly sulfated CS-E might be useful as an anti-HCV drug.

PMID- 22660966
TI  - AuBr(3) mediated glycosidations: synthesis of tetrasaccharide motif of the
      Leishmania donovani lipophosphoglycan.
AB  - Tetrasaccharide cap present in lipophosphoglycan of the Leishmania donovani
      responsible for visceral Leishmaniaisis is synthesized as a fully protected
      propargyl glycoside. AuBr(3) mediated selective glycosylation of propargyl 1,2
      orthoester in the presence of propargyl glycoside is employed as a key step to
      obtain propargyl containing oligomers. Further, propargyl tetrasaccharide is
      connected with a long chain hydrocarbon containing azidothiol functionality
      situated at two terminal ends via 'click' reaction.

PMID- 22660967
TI  - Preterm birth and psychiatric disorders in young adult life.
AB  - CONTEXT: Preterm birth, intrauterine growth restriction, and delivery-related
      hypoxia have been associated with schizophrenia. It is unclear whether these
      associations pertain to other adult-onset psychiatric disorders and whether these
      perinatal events are independent. OBJECTIVE: To investigate the relationships
      among gestational age, nonoptimal fetal growth, Apgar score, and various
      psychiatric disorders in young adult life. DESIGN: Historical population-based
      cohort study. SETTING: Identification of adult-onset psychiatric admissions using
      data from the National Board of Health and Welfare, Stockholm, Sweden.
      PARTICIPANTS: All live-born individuals registered in the nationwide Swedish
      Medical Birth Register between 1973 and 1985 and living in Sweden at age 16 years
      by December 2002 (n=1 301 522). MAIN OUTCOME MEASURES: Psychiatric
      hospitalization with nonaffective psychosis, bipolar affective disorder,
      depressive disorder, eating disorder, drug dependency, or alcohol dependency,
      diagnosed according to the International Classification of Diseases codes for 8
      through 10. Cox proportional hazards regression models were used to estimate
      hazard ratios and 95% CIs. RESULTS: Preterm birth was significantly associated
      with increased risk of psychiatric hospitalization in adulthood (defined as >=16
      years of age) in a monotonic manner across a range of psychiatric disorders.
      Compared with term births (37-41 weeks), those born at 32 to 36 weeks' gestation
      were 1.6 (95% CI, 1.1-2.3) times more likely to have nonaffective psychosis, 1.3
      (95% CI, 1.1-1.7) times more likely to have depressive disorder, and 2.7 (95% CI,
      1.6-4.5) times more likely to have bipolar affective disorder. Those born at less
      than 32 weeks' gestation were 2.5 (95% CI, 1.0-6.0) times more likely to have
      nonaffective psychosis, 2.9 (95% CI, 1.8-4.6) times more likely to have
      depressive disorder, and 7.4 (95% CI, 2.7-20.6) times more likely to have bipolar
      affective disorder. CONCLUSIONS: The vulnerability for hospitalization with a
      range of psychiatric diagnoses may increase with younger gestational age. Similar
      associations were not observed for nonoptimal fetal growth and low Apgar score.

PMID- 22660968
TI  - Dentin regeneration using deciduous pulp stem/progenitor cells.
AB  - Reparative dentin formation is essential for maintaining the integrity of dentin
      structure during disease or trauma. In this study, we investigated
      stem/progenitor cell-based tissue engineering for dentin regeneration in a large
      animal model. Porcine deciduous pulp stem/progenitor cells (PDPSCs) were mixed
      with a beta-tricalcium phosphate (beta-TCP) scaffold for dentin regeneration.
      Different concentrations of PDPSCs were tested to determine the optimal density
      for dentin regeneration. Aliquots of 5*10(5) PDPSCs in 1 mL resulted in the
      highest number of cells attached to the scaffold and the greatest alkaline
      phosphatase activity. We labeled PDPSCs with green fluorescent protein (GFP) and
      used the optimal cell numbers mixed with beta-TCP to repair pulp chamber roof
      defects in the premolars of swine. Four weeks after transplantation, GFP-positive
      PDPSCs were observed in PDPSC-embedded scaffold constructs. At 16 weeks after
      transplantation, the PDPSCs mixed with beta-TCP significantly regenerated the
      dentin-like structures and nearly completely restored the pulp chamber roof
      defects. This study demonstrated that the PDPSC/scaffold construct was useful in
      direct pulp-capping and provides pre-clinical evidence for stem/progenitor cell
      based dentin regeneration.

PMID- 22660969
TI  - Biometeorological and autoregressive indices for predicting olive pollen
      intensity.
AB  - This paper reports on modelling to predict airborne olive pollen season severity,
      expressed as a pollen index (PI), in Cordoba province (southern Spain) several
      weeks prior to the pollen season start. Using a 29-year database (1982-2010), a
      multivariate regression model based on five indices-the index-based model-was
      built to enhance the efficacy of prediction models. Four of the indices used were
      biometeorological indices: thermal index, pre-flowering hydric index, dormancy
      hydric index and summer index; the fifth was an autoregressive cyclicity index
      based on pollen data from previous years. The extreme weather events
      characteristic of the Mediterranean climate were also taken into account by
      applying different adjustment criteria. The results obtained with this model were
      compared with those yielded by a traditional meteorological-based model built
      using multivariate regression analysis of simple meteorological-related
      variables. The performance of the models (confidence intervals, significance
      levels and standard errors) was compared, and they were also validated using the
      bootstrap method. The index-based model built on biometeorological and cyclicity
      indices was found to perform better for olive pollen forecasting purposes than
      the traditional meteorological-based model.

PMID- 22660970
TI  - Risk stratification and prognostic assessment by myocardial perfusion-gated SPECT
      in patients with left bundle-branch block and low-intermediate cardiac risk.
AB  - OBJECTIVE: In high-risk patients with left bundle-branch block (LBBB), functional
      but not perfusion parameters yield incremental prognostic information. The aim of
      our study was to evaluate the prognostic value of gated single photon emission
      computed tomography (SPECT) in low-intermediate risk LBBB patients. METHODS: One
      hundred seventy-six subjects underwent stress-rest dual-day protocol 99mTc
      sestamibi-gated SPECT and were dichotomized in two groups: without LBBB (Group 1,
      n = 86) and with LBBB (Group 2, n = 90). Patients were followed for 32 +/- 18
      months. Cox regression multivariate analysis was used to determine which variable
      was the best predictor of cardiac event. Event-free survival curves were computed
      by Kaplan-Meier method. RESULTS: Myocardial perfusion scintigraphy was abnormal
      in 32 and 60 patients for Groups 1 and 2, respectively (37 vs. 67 %, p < 0.001).
      In Groups 1 and 2, the mean summed stress score (SSS) was 3.7 +/- 5.6 versus 6.7
      +/- 6.4, while the mean summed difference score (SDS) was 1.6 +/- 2.5 versus 2.7
      +/- 3.3 (both p < 0.005); therefore 34 % of patients in Group 1 and 53 % of those
      in Group 2 presented myocardial ischemia. All functional parameters were
      significantly different between the two subsets (all p < 0.005). Follow-up was
      completed in 161 patients (92 %); 10 events occurred in Group 1 and 20 in Group 2
      (14 vs. 25 %). The event-free survival was significantly higher in patients with
      normal than in those with abnormal scan (85 vs. 63 %, p < 0.005); moreover, the
      prognosis of patients with LBBB was significantly worse. At multivariate
      analysis, SDS was found to be the only independent predictor of cardiac events
      both in all patients and in LBBB population (HR 3.08, and HR 4.99, p < 0.05).
      CONCLUSIONS: This is the first study to assess the prognostic value of gated
      SPECT in patients with LBBB and low-intermediate cardiac risk. Both perfusion and
      functional data obtained by gated SPECT are different between patients with and
      without LBBB. However, SDS is the only predictor of events. Thus, the amount of
      reversible ischemia at gated SPECT has a discriminative power in stratifying the
      cardiac risk of LBBB population.

PMID- 22660971
TI  - Early migration of the cemented tibial component of unicompartmental knee
      arthroplasty: a radiostereometry study.
AB  - PURPOSE: Unicompartmental knee arthroplasty has good clinical results but high
      revision rates. A unicompartmental knee arthroplasty design features an all
      polyethylene and conforming tibial component, and we hypothesized that this may
      put at risk its fixation. Implant-to-bone micromotion was measured together with
      relevant clinical outcomes. METHODS: The migration of the tibial component in
      twenty patients was measured at 3, 6, 12 and 24 months, using standard
      radiostereometry, along with the relevant clinical outcomes using the IKS scoring
      system. RESULTS: The eighteen arthroplasties at 24 months were found successful,
      with very good functional (mean 87.7; SD 15.4) and knee scores (mean 94.8; SD
      10.1). The means and the standard deviations of the maximum total point motion
      (MTPM) for the four follow-ups were, respectively, as small as 0.4 +/- 0.1 mm,
      0.6 +/- 0.2 mm, 0.6 +/- 0.3 mm and 0.7 +/- 0.3 mm, an average over all patients
      but one. In this knee, these were 1.6, 2.1, 2.4 and 2.2 mm, therefore not at high
      risk of aseptic loosening according to the literature. Only one knee was found at
      this risk, having the MTPM from 12 to 24 months of 0.5 mm, and the component
      moving and sinking medially, and rising laterally. CONCLUSION: At 2-year follow
      up, a successful implant-to-bone fixation can be achieved in conforming all
      polyethylene cemented tibial component together with excellent clinical outcomes.

PMID- 22660972
TI  - Timing of arthroplasty, what is the influence of nocturnal pain and pain at rest
      on the outcome?
AB  - PURPOSE: The purpose of this study was to investigate whether nocturnal pain and
      pain at rest preoperatively influence the satisfaction in patients after joint
      arthroplasty. The second research question is whether subjective outcome
      (VAS/WOMAC) after hip (THA) or knee arthroplasty (TKA) differs in patients with
      or without nocturnal pain and pain at rest preoperatively compared to those who
      do not. METHODS: A consecutive group of 189 TKAs and 189 THAs was evaluated. The
      influence of pain at rest and nocturnal pain preoperatively on the outcome was
      evaluated by means of a one-way ANOVA. Outcome measurements used were WOMAC, VAS
      pain and VAS Satisfaction. RESULTS: The results show that satisfaction at follow
      up was not influenced by the presence of nocturnal pain or pain at rest
      preoperatively. The presence of nocturnal pain and pain at rest preoperatively
      did result in a poorer WOMAC pain score WOMAC physical impairment score and a
      higher VAS pain at rest and activity after surgery for both THA and TKA.
      CONCLUSION: The results show that the presence of pain at night and pain at rest
      in symptomatic osteoarthritic patients results in worse VAS and WOMAC scores, but
      with similar amounts of satisfaction at follow up.

PMID- 22660973
TI  - The forgotten joint.

PMID- 22660974
TI  - Gradual correction of idiopathic genu varum deformity using the Ilizarov
      technique.
AB  - PURPOSE: Proximal tibial osteotomy is an effective treatment option for genu
      varum deformity among the many other described techniques. The purpose of this
      study is to evaluate the clinical and radiological outcomes and the complications
      in gradual correction of idiopathic genu varum deformity using Ilizarov frame.
      METHODS: Proximal tibial medial opening wedge osteotomy was performed in 21 lower
      limbs of 11 patients, with whom the Ilizarov external fixator was used for
      gradual correction of the varus deformity. The mean age of the patients was 24.8
      years (SD, 5.3). Deformity measurements of conventional mechanical axis
      deviation, mechanical medial proximal tibial angle, mechanical lateral distal
      femoral angle, posterior proximal tibial angle, joint conversion angle, tibio
      femoral angle and tibial slope were compared. RESULTS: The mean time for removal
      of the Ilizarov fixator was 24.7 weeks. At the last follow-up, the mean of
      Hospital for Special Surgery knee score increased, and the mean mechanical medial
      proximal tibial angle, tibio-femoral angle and conventional mechanical axis
      deviation improved. The differences between preoperative and postoperative
      posterior proximal tibial angle, mechanical lateral distal femoral angle, joint
      conversion angle and tibial slope were not significant. Ten complications were
      observed, of which 8 were minor complications and 2 were minor complications.
      CONCLUSION: With a few complications, normal alignment and orientation of lower
      extremity can be established in patients with idiopathic genu varum deformity
      through gradual correction using a Ilizarov fixator. LEVEL OF EVIDENCE:
      Retrospective case series, Level IV.

PMID- 22660975
TI  - Protective effect of Homer 1a on tumor necrosis factor-alpha with cycloheximide
      induced apoptosis is mediated by mitogen-activated protein kinase pathways.
AB  - Although Homer 1, of the postsynaptic density, regulates apoptosis, the signaling
      mechanisms are not fully elucidated. In this study, we found that tumor necrosis
      factor-alpha (TNF-alpha)/cycloheximide (CHX) treatment transiently increased
      Homer 1a (the short variant of Homer 1), but did not affect Homer 1b/c (the long
      variant of Homer 1). Overexpression of Homer 1a blocked TNF-alpha/CHX-induced
      apoptotic cell death, whereas inhibition of Homer 1a induction enhanced the pro
      apoptotic effect of TNF-alpha/CHX treatment. Moreover, brain-derived neurotrophic
      factor, as a potential activator of endogenous Homer 1a, inhibited apoptotic cell
      death after TNF-alpha/CHX treatment through induction of Homer 1a. Since three
      major mitogen-activated protein kinase (MAPK) pathways have important roles in
      apoptosis, we examined if Homer 1a is involved in the effects of MAPK pathways on
      apoptosis. It was shown that inhibition of the ERK1/2 pathway increased the
      expression and the protective effect of Homer 1a, but inhibition of the p38
      pathway produced the opposite effect. Cross-talk among MAPK pathways was also
      associated with the regulation of Homer 1a during apoptotic cell death. Blocking
      the p38 pathway increased the activity in the ERK1/2 pathway, while inhibition of
      ERK1/2 pathway abolished the effect of p38 inhibitor on Homer 1a. Furthermore,
      Homer 1a reversely affected the activation of MAPK pathways. These findings
      suggest that Homer 1a plays an important role in the prevention of apoptotic cell
      death and contributes to distinct regulatory effects of MAPK pathways on
      apoptotic cell death.

PMID- 22660976
TI  - The role of PARP1 in the DNA damage response and its application in tumor
      therapy.
AB  - Single-strand break repair protein poly(ADP-ribose) polymerase 1 (PARP1)
      catalyzes the poly(ADP-ribosyl)ation of many key proteins in vivo and thus plays
      important roles in multiple DNA damage response pathways, rendering it a
      promising target in cancer therapy. The tumor-suppressor effects of PARP
      inhibitors have attracted significant interest for development of novel cancer
      therapies. However, recent evidence indicated that the underlying mechanism of
      PARP inhibitors in tumor therapy is more complex than previously expected. The
      present review will focus on recent progress on the role of PARP1 in the DNA
      damage response and PARP inhibitors in cancer therapy. The emerging resistance of
      BRCA-deficient tumors to PARP inhibitors is also briefly discussed from the
      perspective of DNA damage and repair. These recent research advances will inform
      the selection of patient populations who can benefit from the PARP inhibitor
      treatment and development of effective drug combination strategies.

PMID- 22660979
TI  - Adolescent baseball pitching technique: lower extremity biomechanical analysis.
AB  - Documentation of the lower extremity motion patterns of adolescent pitchers is an
      important part of understanding the pitching motion and the implication of lower
      extremity technique on upper extremity loads, injury and performance. The purpose
      of this study was to take the initial step in this process by documenting the
      biomechanics of the lower extremities during the pitching cycle in adolescent
      pitchers and to compare these findings with the published data for older
      pitchers. Three-dimensional motion analysis using a comprehensive lower extremity
      model was used to evaluate the fast ball pitch technique in adolescent pitchers.
      Thirty-two pitchers with a mean age of 12.4 years (range 10.5-14.7 years) and at
      least 2 years of experience were included in this study. The pitchers showed a
      mean of 49 +/- 12 degrees  of knee flexion of the lead leg at foot contact. They
      tended to maintain this position through ball release, and then extended their
      knee during the follow through phase (ball release to maximal internal
      glenohumeral rotation). The lead leg hip rapidly progressed into adduction and
      flexion during the arm cocking phase with a range of motion of 40 +/- 10 degrees 
      adduction and 30 +/- 13 degrees  flexion. The lead hip mean peak adduction
      velocity was 434 +/- 83 degrees /s and flexion velocity was 456 +/- 156 degrees
      /s. Simultaneously, the trailing leg hip rapidly extended approaching to a mean
      peak extension of -8 +/- 5 degrees  at 39% of the pitch cycle, which is close to
      passive range of motion constraints. Peak hip abduction of the trailing leg at
      foot contact was -31 +/- 12 degrees , which also approached passive range of
      motion constraints. Differences and similarities were also noted between the
      adolescent lower extremity kinematics and adult pitchers; however, a more
      comprehensive analysis using similar methods is needed for a complete comparison.

PMID- 22660978
TI  - Prognostic analysis of chronic myeloid leukemia in Chinese population in an
      imatinib era.
AB  - We evaluated the outcomes of chronic myeloid leukemia (CML) patients receiving
      imatinib treatment in chronic (CP), accelerated (AP), and blast crisis (BP)
      phases. The single-institution treatment experiences of Chinese patients with CML
      were presented. A total of 275 CML patients (CP, 210; AP, 24; and BP, 41) who
      received imatinib between February 2001 and April 2008 were enrolled in this
      study. We evaluated the treatment responses (hematologic, cytogenetic, and
      molecular), overall survival (OS), event-free survival (EFS), and prognostic
      factors of outcome. At the cut-off point, the complete cytogenetic response
      (CCyR) and complete molecular response rates of patients in the CP were 84.7% and
      61.9%, respectively, which were significantly higher than those of patients in
      the AP (50% and 29.1%, respectively, both P < 0.001) and BP (24.3% and 9.7%,
      respectively, both P < 0.001). The estimated five-year OS and five-year EFS rates
      were 93.2% and 86.4% for CP patients, as well as 64.5% and 50.9% for AP patients,
      which were significantly higher than those for BP patients (P < 0.001). In CP
      patients, univariate analysis revealed that early treatment with imatinib,
      achieving CCyR within 12 months, additional cytogenetic abnormalities, and kinase
      domain mutations were associated with the treatment outcome. More patients are
      needed to carry out multivariate analysis.

PMID- 22660977
TI  - Nucleic acid-based diagnostics for infectious diseases in public health affairs.
AB  - Infectious diseases, mostly caused by bacteria and viruses but also a result of
      fungal and parasitic infection, have been one of the most important public health
      concerns throughout human history. The first step in combating these pathogens is
      to get a timely and accurate diagnosis at an affordable cost. Many kinds of
      diagnostics have been developed, such as pathogen culture, biochemical tests and
      serological tests, to help detect and fight against the causative agents of
      diseases. However, these diagnostic tests are generally unsatisfactory because
      they are not particularly sensitive and specific and are unable to deliver speedy
      results. Nucleic acid-based diagnostics, detecting pathogens through the
      identification of their genomic sequences, have shown promise to overcome the
      above limitations and become more widely adopted in clinical tests. Here we
      review some of the most popular nucleic acid-based diagnostics and focus on their
      adaptability and applicability to routine clinical usage. We also compare and
      contrast the characteristics of different types of nucleic acid-based
      diagnostics.

PMID- 22660980
TI  - Effects of the magnetic resonance field on breast tissue expanders.
AB  - BACKGROUND: Tissue expansion for breast reconstruction after mastectomy is a safe
      and effective procedure. A magnetic resonance imaging (MRI) scan can be requested
      for patients with a breast expander to evaluate concurrent diseases. The
      electromagnetic field of the MR can interfere with biomedical devices, resulting
      in potential hazards, compromising the diagnosis, or creation of artifacts.
      METHODS: Four tissue expanders with an integrated magnetic valve were tested. The
      temperature increase was measured using an infrared camera in the MR scanner. The
      expanders were tested (half-full and full of saline solution) both free in air
      and immersed in a phantom. The ferromagnetic properties of the devices were
      assessed using the deflection angle method. To evidence artifacts due to the
      presence of the expander, MR images were acquired for expanders tested in air and
      in the phantom. A valve localization test was performed after MRI analysis.
      RESULTS: A slight increase in temperature was demonstrated, without any clinical
      significance. The deflection angle due to the magnetic field depends on the
      distance from the bore of the magnet. The angle is higher when the device is
      closer to the bore. The presence of the magnetic valve influences the MRI signal,
      creating artifacts on the acquired images, even far from the valve itself. The
      valve localization test allowed verification of correct valve functioning for all
      the expanders after the MRI analysis. CONCLUSIONS: Under selected conditions, MRI
      scans can be feasible. Heating is not expected to be a major concern, whereas
      valve displacement could happen in certain clinical conditions. The presence of
      artifacts is almost unavoidable. LEVEL OF EVIDENCE III: 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- 22660981
TI  - A new umbilical reconstruction technique used for 306 consecutive
      abdominoplasties.
AB  - BACKGROUND: The search for a natural-appearing umbilicus that does not compromise
      the aesthetic outcome of abdominoplasty began in the 1950s and coincides with the
      period that saw increasing exposure of the female body. Since then, umbilical
      transposition has been favored by most surgeons. METHODS: This report describes a
      new technique for umbilical reconstruction using a small X-shaped incision that
      creates four V-shaped flaps, which are sutured to the aponeurosis with absorbable
      sutures. This technique was used for 306 consecutive abdominoplasty patients, and
      a survey was performed to determine their level of satisfaction with the surgical
      outcome. RESULTS: A natural-appearing new umbilicus was created with no visible
      scars, a low complication rate (9 %), and a high level of patient satisfaction.
      CONCLUSIONS: The described technique had a low complication rate and allowed the
      creation of a new umbilicus with a natural appearance in a rapid, safe, and
      simple manner. LEVEL OF EVIDENCE IV: This journal requires that authors assign a
      level of evidence to each article.

PMID- 22660982
TI  - Photochemical performance of the acidophilic red alga Cyanidium sp. in a pH
      gradient.
AB  - The acidophilic red alga Cyanidium sp. is one of the dominant mat-forming species
      in the highly acidic waters of Rio Tinto, Spain. The culture of Cyanidium sp.,
      isolated from a microbial mat sample collected at Rio Tinto, was exposed to 9
      different pH conditions in a gradient from 0.5 to 5 for 24 h and its
      physiological status evaluated by variable chlorophyll a fluorescence kinetics
      measurements. Maximum quantum yield was determined after 30 min, 1 h, 2 h, 4 h, 6
      h and 24 h of exposure after 15 min dark adaptation. The effect of pH on
      photochemical activity of Cyanidium sp. was observable as early as 30 min after
      exposure and the pattern remained stable or with only minor modifications for 24
      h. The optimum pH ranged from 1.5 to 2.5. A steep decrease of the photochemical
      activity was observed at pH below 1 even after 30 min of exposure. Although the
      alga had tolerated the exposure to pH = 1 for at least 6 h, longer (24 h)
      exposure resulted in reduction of the photochemical activity. At pH above 2.5,
      the decline was more moderate and its negative effect on photochemistry was less
      severe. According to the fluorescence measurements, the red alga Cyanidium sp. is
      well-adapted to prevailing pH at its original locality at Rio Tinto, i.e. pH of 1
      to 3. The short-term survival in pH < 1.5 may be adaptation to rare exposures to
      such low pH in the field. The tolerance of pH above 3 could be caused by
      adaptation to the microenvironment of the inner parts of microbial mats in which
      Cyanidium sp. usually dominates and where higher pH could occur due to
      photosynthetic oxygen production.

PMID- 22660983
TI  - Radiolytic studies of naphthalene in the presence of water.
AB  - Naphthalene is an interesting candidate to study in the framework of organic
      delivery to planetary surfaces as well as in the origin of life. Additionally,
      naphthalene is of environmental interest, because of its chronic and acute
      effects on living systems, such as humans and animals (e.g. moths). Naphthalene
      has been well studied in both fields. In this paper we give an overview of
      radiolytic studies of naphthalene in the presence of both liquid water and water
      ice. From our review it appears that OH radicals are formed both in liquid water
      and in interstellar ices and that these radicals play a considerable role in the
      degradation of naphthalene. However, it also appears that upon irradiation of
      naphthalene in liquid water, hydrogen peroxide, a species that accelerates
      naphthalene degradation, is formed. Based on this review we suggest that the role
      of hydrogen peroxide in interstellar ices should be further investigated.

PMID- 22660984
TI  - 3D cone-beam CT guidance, a novel technique in renal biopsy--results in 41
      patients with suspected renal masses.
AB  - OBJECTIVE: To determine whether 3D cone-beam computed tomography (CBCT) guidance
      allows safe and accurate biopsy of suspected small renal masses (SRM), especially
      in hard-to-reach anatomical locations. MATERIALS AND METHODS: CBCT guidance was
      used to perform 41 stereotactic biopsy procedures of lesions that were
      inaccessible for ultrasound guidance or CT guidance. In CBCT guidance, a 3D
      volume data set is acquired by rotating a C-arm flat-panel detector angiosystem
      around the patient. In the data set, a needle trajectory is determined and, after
      co-registration, a fusion image is created from fluoroscopy and a slice from the
      data set, enabling the needle to be positioned in real time. RESULTS: Of the 41
      lesions, 22 were malignant, 17 were benign, and 2 were nondiagnostic. The two
      nondiagnostic lesions proved to be renal cell carcinoma. There was no growth
      during follow-up imaging of the benign lesions (mean 29 months). This resulted in
      a sensitivity, specificity, PPV, NPV, and accuracy of 91.7, 100, 100, 89.5, and
      95.1%, respectively. Mean dose-area product value was 44.0 Gy.cm(2) (range 16.5
      126.5). There was one minor bleeding complication. CONCLUSION: With CBCT
      guidance, safe and accurate biopsy of a suspected SRM is feasible, especially in
      hard-to-reach locations of the kidney. KEY POINTS : * Cone-beam computed
      tomography has potential advantages over conventional CT for interventional
      procedures. * CBCT guidance incorporates 3D CBCT data, fluoroscopy, and guidance
      software. * In hard-to-reach renal masses, CBCT guidance offers an alternative
      biopsy method. * CBCT guidance offers good outcome and safety and has potential
      clinical significance.

PMID- 22660985
TI  - A novel binding protein of single-minded 2: the mitotic arrest-deficient protein
      MAD2B.
AB  - Single-minded 2 (Sim2) gene, located at the Down syndrome (DS) critical region,
      is thought to be particularly important because of its critical role in the
      development of the central nervous system (CNS) and its overexpression resulting
      in impairment of learning and memory which is similar to that in DS. However, its
      exact role in DS still remains elusive. Using a yeast two-hybrid interaction
      trap, we identified the mitotic arrest-deficient protein MAD2B as a novel Sim2
      binding protein. Through confocal laser scanning microscopy, we found that Sim2
      and MAD2B colocalized in rat cortex neurons. This interaction between Sim2 and
      MAD2B was also confirmed by co-immunoprecipitation. Moreover, levels of mRNA and
      protein of both Sim2 and MAD2B were regulated during nervous development as
      detected by quantitative RT-PCR and western blot analysis. We also found that
      overexpression of Sim2 affected the distribution of MAD2B in primary culture
      neurons. The results of confocal laser scanning microscopy and co
      immunoprecipitation indicated that in neurons, MAD2B interacted with clathrin
      light chain A, which is best known for its role in endocytosis. In addition, it
      was found that overexpression of Sim2 or MAD2B caused deficits in clathrin
      mediated endocytosis. Furthermore, overexpression of both MAD2B and Sim2
      exacerbates their own inhibitory effect on transferrin uptake. These results
      suggest that MAD2B may mediate Sim2 function during development in CNS and
      thereby play a critical role in pathophysiological mechanisms in DS.

PMID- 22660987
TI  - Faculty members' perceptions of advising versus mentoring: does the name matter?
AB  - The recommendations, during the past 20 years, to improve PhD scientific training
      and graduate school success, have focused on the significance of mentoring. It is
      well established that PhD students with mentors have significantly more success
      in graduate school as demonstrated by publishing papers before they graduate and
      by making presentations. Have faculty and academic institutions embraced the
      mentoring role? This study explores the views of 3,500 scientists who have
      primary responsibilities to educate PhD and MD/PhD students. Faculty members
      report they are more likely to prefer being viewed as advisors (54 %) than
      mentors (38 %). Through an examination of perceptions about specific
      responsibilities of advisors and mentors, faculty members provide a description
      of their culture and the expectations they have about themselves and others. One
      would expect that because mentoring requires additional time and involvement that
      faculty would report differences between advising and mentoring. However, faculty
      members perceive few differences between advisors and mentors. We examine the
      implications of these findings. Future scientists need to be confident their
      education includes the opportunity to acquire the best possible research skills.
      To develop advisors who have the ability to provide this training, the process
      begins by defining role expectations and responsibilities and preparing advisors
      to interact with doctoral students in ways comparable to mentors. We expect
      faculty members to know how to teach and how to mentor; yet, we rarely discuss
      how to develop and shape the necessary skills of advisors so, that they more
      closely resemble those of mentors. 

PMID- 22660986
TI  - Improvements in cystic fibrosis lung disease and airway inflammation associated
      with etanercept therapy for rheumatoid arthritis: a case report.
AB  - Cystic fibrosis (CF) lung pathology is characterized by excessive neutrophilic
      inflammation and high tumor necrosis factor-alpha (TNF-alpha) levels. A
      cornerstone of CF management is reduction of the inflammatory burden in the lung.
      We present the case of a 19-year-old CF patient who demonstrated significant
      clinical improvement in her lung disease associated with a reduction in sputum
      percent neutrophils, following commencement of etanercept (TNF-alpha antagonist)
      for rheumatoid arthritis. She has not had any infectious complications or other
      significant adverse effects during 2 years of treatment. It may be time to
      reconsider TNF-alpha antagonists as potential anti-inflammatory agents for CF
      lung disease.

PMID- 22660988
TI  - Ethical decision making in the conduct of research: role of individual,
      contextual and organizational factors. Commentary on "Science, human nature, and
      a new paradigm for ethics education".
AB  - Despite the importance of scientific integrity to the well-being of society,
      recent findings suggest that training and mentoring in the responsible conduct of
      research are not very reliable or effective inhibitors of research misbehavior.
      Understanding how and why individual scientists decide to behave in ways that
      conform to or violate norms and standards of research is essential to the
      development of more effective training programs and the creation of more
      supportive environments. Scholars in business management, psychology, and other
      disciplines have identified many important factors that affect ethical behavior,
      including individual, contextual, and organizational factors. Surprisingly little
      research has been conducted to examine the role of these factors in either the
      development of ethical decision-making skills, or their applicability to ethical
      issues commonly encountered in research and other scholarly and professional
      activities. Interdisciplinary approaches combined with research and discipline
      relevant paradigms should greatly enhance understanding of the individual
      contextual and organizational factors involved in ethical and unethical research
      conduct. Such studies will inform and facilitate the development of more
      effective ethics education programs in the sciences and engineering professions.

PMID- 22660989
TI  - [Editorial on the contribution "Challenges for the German Health Care System"].

PMID- 22660990
TI  - Challenges for the German Health Care System.
AB  - The German Health Care System (GHCS) faces many challenges among which an aging
      population and economic problems are just a few. The GHCS traditionally
      emphasised equity, universal coverage, ready access, free choice, high numbers of
      providers and technological equipment; however, real competition among health
      care providers and insurance companies is lacking. Mainly in response to
      demographic changes and economic challenges, health-care reforms have focused on
      cost containment and to a lesser degree also quality issues. In contrast,
      generational accounting, priorisation and rationing issues have thus far been
      completely neglected. The paper discusses three important areas of health care in
      Germany, namely the funding process, hospital management and ambulatory care,
      with a focus on cost control mechanisms and quality improving measures as the
      variables of interest. Health Information Technology (HIT) has been identified as
      an important quality improvement tool. Health Indicators have been introduced as
      possible instruments for the priorisation debate.

PMID- 22660991
TI  - [Laxative use and satisfaction of chronically constipated women - a survey of
      female patients and gastroenterologists in Germany].
AB  - OBJECTIVE: Data were collected concerning the patient satisfaction in the
      treatment of chronic constipation with laxatives. METHOD: An internet-based
      survey of female patients with chronic constipation and an online enquiry
      addressed to gastroenterologists in Germany were carried out. RESULTS: 492 female
      patients and 104 physicians participated in the survey. Only 20 % of the patients
      were currently consuming laxatives. Around one-third of those not using laxatives
      have had unsatisfactory experiences. Only 32 % of the participants currently
      taking laxatives were totally satisfied with their drugs. As a general rule
      several different preparations were tried. The laxatives most closely associated
      with satisfied patients were bisacodyl and sodium picosulfate, followed by
      macrogol. The main reasons for dissatisfaction were an insufficient relief of the
      constipation and a bloated feeling. The majority of the participants expressed an
      interest in new drugs for the treatment of constipation. The participating
      physicians stated that they saw several female patients per week who were not
      satisfied with their constipation treatment, but probably overestimate the
      proportion. CONCLUSION: The present survey shows that the majority of women
      suffering from constipation do not take laxatives and also that about half of
      them were not satisfied with the agents tried. Only about one-third of the
      chronic users were totally satisfied. Thus, there is a clear need for new
      laxatives.

PMID- 22660992
TI  - [Pyogenic liver abscess: a retrospective patient study].
AB  - INTRODUCTION: Pyogenic liver abscess (PLA) is a disease with changing origins as
      well as diagnostic and therapeutic options in the last decades. MATERIALS AND
      METHODS: A retrospective study of the last 20 patients treated at a
      gastroenterological department of a university clinic for the major diagnosis of
      PLA was conducted. Epidemiological, clinical, microbiological and therapeutic
      aspects were recorded. RESULTS: 75 % of the patients were male. The mean age was
      51.7 +/- 16.6 years. Most of PLA (70 %) had a hepatobiliary origin. Diabetes
      mellitus (25 %) and cholangiocarcinoma (20 %) were the major risk factors for
      PLA. Crohn's disease was a possible cause in at least one patient. Fever (70 %)
      and tachycardia (50 %) were the most common symptoms. The C-reactive protein was
      elevated in all patients. Enterococci (> 40 %) and anaerobes (> 20 %) were the
      most frequent organisms in abscess cultures, Escherichia coli (25 %) was the most
      frequent organism in blood cultures. DISCUSSION: The clinical presentation of PLA
      is usually non-specific. Therefore especially with patients having typical risk
      factors the differential diagnosis of PLA should be considered. Particularly
      patients suffering from PLA without any pre-existing illness should be examined
      for an underlying disease.

PMID- 22660993
TI  - [Acute respiratory failure after metoclopramide for methemoglobinemia - a rare
      and potentially life-threatening side effect].
AB  - HISTORY AND CLINICAL FINDINGS: A 85-year-old patient, initially treated for
      aspiration pneumonia on the intensive care unit acutely complained again of
      nausea which was immediately treated by an i. v. bolus of metoclopramide (MCP).
      Without another incident of aspiration she subsequently developed acutely massive
      dyspnoea, increasing cyanosis and somnolence. INVESTIGATION: On physical exam the
      patient showed tachycardia, dyspnoea and progressive somnolence. Laboratory
      investigation showed no significant abnormalities other than improving
      inflammatory markers. Computer tomography of the chest as well as bronchoscopy
      also revealed no pathologies. Blood gas analysis (BGA) however showed a massive
      increase in methemoglobinemia from 0.5 % just prior to MCP injection to 53.1 %
      after MCP injection; simultaneously the pO2 decreased from 74 auf 54 mmHg and the
      pCO2 from 37.7 to 34.1 mmHg. TREATMENT AND COURSE: Instant therapy with toluidine
      blue led to a dramatic improvement of the patient's symptoms as well as a rapid
      normalisation of the pathological BGA. Soon after the patient could be dismissed.
      CONCLUSION: The development of a severe and acute methemoglobinemia following the
      administration of MCP is described in this case report. Rapidly evolving dyspnoea
      following administration of MCP should instantly lead to the consideration of
      acute methemoglobinemia as differential diagnosis. Rapid diagnosis by blood gas
      analysis and instant therapy by toloudine blue (TB) can effectively prevent a
      potentially lethal course. The pathogenesis, clinical presentation, diagnosis and
      therapy for methemoglobinemia are discussed.

PMID- 22660994
TI  - A 45-year-old female with hypokalemic rhabdomyolysis due to VIP-producing
      composite pheochromocytoma.
AB  - The watery diarrhea, hypokalemia and achlorhydria (WHDA) syndrome due to
      vasoactive intestinal polypeptide (VIP)-producing extra-pancreatic tumors is
      rare. We report on a 45-year-old woman who suffered from persistent secretory
      diarrhea for six years and who was admitted to hospital with complaints of
      muscular weakness and myalgia. Biochemical testing revealed pronounced
      rhabdomyolysis due to severe hypokalemia. Gastrointestinal evaluation of long
      standing diarrhea including endoscopy of the upper and lower gastrointestinal
      tract and the small intestine did not show any pathologies. An abdominal computed
      tomography scan revealed a mass of 4 * 5 cm in the left adrenal gland
      demonstrating a strong uptake in the 123I-labelled metaiodobenzylguanidine
      scintigraphy. Plasma levels of chromogranin A, calcitonin, parathormone, basal
      renin and most prominently VIP were increased in line with a increased 24 hour
      urinary secretion of noradrenaline, dopamine, normetanephrine and vanillymandelic
      acid. A WDHA (watery diarrhea, hypokalaemia, achlorhydria) syndrome with
      hypokalemic rhabdomyolysis due to a VIP-producing adrenal tumor was diagnosed
      that was removed surgically. The histological evaluation demonstrated a composite
      pheochromocytoma. Diarrhea stopped immediately after surgery together with a
      normalization of laboratory parameters. In conclusion, this case report focuses
      on the rare clinical presentation of secretory diarrhea and electrolyte
      disturbances in combination with hypokalemic rhabdomyolysis which was caused by a
      VIP-producing composite pheochromocytoma.

PMID- 22660995
TI  - [Postoperative morbidity after bowel resections in patients with Crohn's disease:
      risk, management strategies, prevention].
AB  - The postoperative morbidity rate following bowel resections for Crohn's disease
      is higher than for other benign disease. The incidence of postoperative
      intraabdominal septic complications (anastomotic leak, bowel fistula,
      intraabdominal abscess, peritonitis) is 5 - 30 %. Preoperative weight loss,
      prolonged refractory symptoms and penetrating disease behaviour are significant
      determinants of postoperative complication risk. Preoperative enteral nutrition,
      antibiotics, percutaneous abscess drainage and cessation of steroids might reduce
      the risk of surgery, however, more evidence is needed. The intake of
      immunosuppressive agents (mainly, azathioprine) can be continued perioperatively.
      The occurrence of postoperative intraabdominal septic complications is associated
      with an increased risk of surgical recurrence in patients with terminal ileitis,
      however, the long-term prognosis could be improved in the latter patients by
      secondary fecal diversion. There is no association between postoperative
      morbidity and long-term outcome in patients with Crohn's colitis.

PMID- 22660996
TI  - [Radiofrequency ablation using the HALO system in the treatment of Barrett's
      oesophagus].
AB  - In recent years radiofrequency ablation using the HALO system in the treatment of
      Barrett's oesophagus has become established. The HALO system consists of a
      circumferential ablation using a balloon-based electrode and a focal ablation
      using an endoscope-mounted bipolar electrode on an articulated platform. In
      combination with prior endoscopic resection radiofrequency ablation is a valuable
      therapeutic technique in selected patients with early Barrett's neoplasia.
      Clinical trials demonstrate that radiofrequency ablation is highly effective and
      durable, has low complication rates, preserves the functional integrity of the
      oesophagus, is easy to apply and the regenerating neosquamous epithelium is free
      of pre-existing oncogenetic alterations.

PMID- 22660997
TI  - [Reduced risk for colorectal adenomatous polyps with high intake of
      polyunsaturated fatty acids in women].

PMID- 22660998
TI  - Consciousness: today.

PMID- 22660999
TI  - Heart rate variability and the central autonomic network in the severe disorder
      of consciousness.
AB  - OBJECTIVE: To review the applicability of heart rate variability measures in
      research on severe disorder of consciousness. METHODS: The available evidence on
      the correlation between heart rate variability measures and the outcome or
      residual functional state/responsiveness of severely brain-injured patients
      (including those in vegetative or minimally conscious states) are reviewed and
      discussed with reference to the central autonomic network model. RESULTS AND
      CONCLUSION: Heart rate variability analyses appear to be applicable to assess
      residual or emerging (higher level) function in brain-injured patients with
      disordered consciousness and to predict outcome. In this regard, the central
      autonomic network model is heuristic in the understanding of heart rate
      variability descriptors of the central nervous system/autonomic systems
      relationship.

PMID- 22661000
TI  - Decreasing incidence of paroxysmal sympathetic hyperactivity syndrome in the
      vegetative state.
AB  - OBJECTIVE: To update knowledge of the incidence of paroxysmal sympathetic
      hyperactivity (PSH, also referred to as dysautonomia), an emergency condition
      tentatively attributed to sympathetic paroxysms or diencephalic-hypothalamic
      disarrangement associated with severe diffuse brain axonal damage or hypoxia.
      This condition is reportedly common in the vegetative state, threatens survival
      and affects outcome. METHODS: The results of a retrospective study on 333
      subjects in a vegetative state admitted to a dedicated unit in 1998-2005 are
      compared with a survey on patients admitted to the same unit in 2006-2010.
      RESULTS AND COMMENT: In the 1998-2005 period, the incidence of PSH was 32% and
      16% in post-traumatic and non-traumatic patients, respectively. It decreased to
      18% and 7% in the 2006-2010 period. The PSH duration and the time spent in
      emergency units before admission and in the dedicated unit for the vegetative
      state after admission also decreased significantly. Incidence was greater among
      post-traumatic- patients; its effect on outcome does not appear to have changed.

PMID- 22661001
TI  - Recovery of cognitive function during comprehensive rehabilitation after severe
      traumatic brain injury.
AB  - OBJECTIVE: To explore the course and timing of functional recovery in patients
      who have emerged from coma after undergoing severe traumatic brain injury.
      METHODS: An observational study involving 19 patients with traumatic brain injury
      recovered from coma who underwent holistic, intensive and multidisciplinary
      neurorehabilitation. Daily performance in each cognitive function (long-term
      memory, short-term memory, orientation, calculation, attention, mental control,
      automation, and planning) was clinically scored and compared at admission and
      discharge. RESULTS: The course of cognitive recovery after post-traumatic coma is
      not uniform, offering a curve with many ups, downs and plateaus. To achieve a
      good response and outcome nearing normalcy, a patient needs over 300 h of
      intensive rehabilitation. CONCLUSION: The consolidation of functional recovery in
      patients with traumatic brain injury requires time and adequate training, and
      discharge is not recommended until cognitive improvement is established.

PMID- 22661002
TI  - Neurorehabilitation for severe disorder of consciousness: the S. Anna - RAN
      operational model.
AB  - The operational model and strategies designed for use in the S. Anna - Research
      in Advanced Neurorehabilitation Institute for the care and neurorehabilitation of
      subjects in the vegetative or minimally conscious states are described here. A
      total of 722 patients were admitted, cared for and discharged from the institute
      in the period 1998-2009. Application of the model approach has progressively
      shortened the time of hospitalization and rehabilitation and reduced costs.

PMID- 22661004
TI  - Improving the description of metabolic networks: the TCA cycle as example.
AB  - To collect the ever-increasing yet scattered knowledge on metabolism, multiple
      pathway databases like the Kyoto Encyclopedia of Genes and Genomes have been
      created. A complete and accurate description of the metabolic network for human
      and other organisms is essential to foster new biological discoveries. Previous
      research has shown, however, that the level of agreement among pathway databases
      is surprisingly low. We investigated whether the lack of consensus among
      databases can be explained by an inaccurate representation of the knowledge
      described in scientific literature. As an example, we focus on the well-known
      tricarboxylic acid (TCA) cycle and evaluated the description of this pathway as
      found in a comprehensive selection of 10 human metabolic pathway databases.
      Remarkably, none of the descriptions given by these databases is entirely
      correct. Moreover, consensus exists on only 3 reactions. Mistakes in pathway
      databases might lead to the propagation of incorrect knowledge, misinterpretation
      of high-throughput molecular data, and poorly designed follow-up experiments. We
      provide an improved description of the TCA cycle via the community-curated
      database WikiPathways. We review various initiatives that aim to improve the
      description of the human metabolic network and discuss the importance of the
      active involvement of biological experts in these.

PMID- 22661005
TI  - Peptides based on the presenilin-APP binding domain inhibit APP processing and
      Abeta production through interfering with the APP transmembrane domain.
AB  - Presenilins (PSENs) form the catalytic component of the gamma-secretase complex,
      responsible for intramembrane proteolysis of amyloid precursor protein (APP) and
      Notch, among many other membrane proteins. Previously, we identified a PSEN1
      binding domain in APP, encompassing half of the transmembrane domain following
      the amyloid beta (Abeta) sequence. Based on this, we designed peptides mimicking
      this interaction domain with the aim to selectively block APP processing and
      Abeta generation through interfering with enzyme-substrate binding. We identified
      a peptide sequence that, when fused to a virally derived translocation peptide,
      significantly lowered Abeta production (IC(50): 317 nM) in cell-free and cell
      based assays using APP-carboxy terminal fragment as a direct gamma-secretase
      substrate. Being derived from the APP sequence, this inhibitory peptide did not
      affect NotchDeltaE gamma-cleavage, illustrating specificity and potential
      therapeutic value. In cell-based assays, the peptide strongly suppressed APP
      shedding, demonstrating that it exerts the inhibitory effect already upstream of
      gamma-secretase, most likely through steric hindrance.

PMID- 22661006
TI  - Endogenous prion protein conversion is required for prion-induced neuritic
      alterations and neuronal death.
AB  - Prions cause fatal neurodegenerative conditions and result from the conversion of
      host-encoded cellular prion protein (PrP(C)) into abnormally folded scrapie PrP
      (PrP(Sc)). Prions can propagate both in neurons and astrocytes, yet neurotoxicity
      mechanisms remain unclear. Recently, PrP(C) was proposed to mediate neurotoxic
      signaling of beta-sheet-rich PrP and non-PrP conformers independently of
      conversion. To investigate the role of astrocytes and neuronal PrP(C) in prion
      induced neurodegeneration, we set up neuron and astrocyte primary cocultures
      derived from PrP transgenic mice. In this system, prion-infected astrocytes
      delivered ovine PrP(Sc) to neurons lacking PrP(C) (prion-resistant), or
      expressing a PrP(C) convertible (sheep) or not (mouse, human). We show that
      interaction between neuronal PrP(C) and exogenous PrP(Sc) was not sufficient to
      induce neuronal death but that efficient PrP(C) conversion was required for prion
      associated neurotoxicity. Prion-infected astrocytes markedly accelerated
      neurodegeneration in homologous cocultures compared to infected single neuronal
      cultures, despite no detectable neurotoxin release. Finally, PrP(Sc) accumulation
      in neurons led to neuritic damages and cell death, both potentiated by glutamate
      and reactive oxygen species. Thus, conversion of neuronal PrP(C) rather than
      PrP(C)-mediated neurotoxic signaling appears as the main culprit in prion-induced
      neurodegeneration. We suggest that active prion replication in neurons sensitizes
      them to environmental stress regulated by neighboring cells, including
      astrocytes.

PMID- 22661007
TI  - miR-31 is a negative regulator of fibrogenesis and pulmonary fibrosis.
AB  - Aberrant expression of miRNAs is closely associated with initiation and
      progression of pathological processes, including diabetes, cancer, and
      cardiovascular disease. However, the role of miRNAs in lung fibrosis is not well
      characterized. We sought to determine the role of miR-31 in regulating the
      fibrogenic, contractile, and migratory activities of lung fibroblasts and
      modulating of pulmonary fibrosis in vivo. In vivo lung fibrosis models and ex
      vivo cell culture systems were employed. Real-time PCR and Western blot analysis
      were used to determine gene expression levels. miR-31 mimics or inhibitors were
      transfected into pulmonary fibroblasts. Fibrogenic, contractile, and migratory
      activities of lung fibroblasts were determined. We found that miR-31 expression
      is reduced in the lungs of mice with experimental pulmonary fibrosis and in IPF
      fibroblasts. miR-31 inhibits the profibrotic activity of TGF-beta1 in normal lung
      fibroblasts and diminishes the fibrogenic, contractile, and migratory activities
      of IPF fibroblasts. In these experiments, miR-31 was shown to directly target
      integrin alpha(5) and RhoA, two proteins that have been shown to regulate
      activation of fibroblasts. We found that levels of integrin alpha(5) and RhoA are
      up-regulated in fibrotic mouse lungs. Knockdown of integrin alpha(5) and RhoA
      attenuated fibrogenic, contractile, and migratory activities of IPF fibroblasts,
      in a manner similar to that observed with miR-31. We also found that introduction
      of miR-31 ameliorated experimental lung fibrosis in mice. Our data suggest that
      miR-31 is an important regulator of the pathological activities of lung
      fibroblasts and may be a potential target in the development of novel therapies
      to treat pathological fibrotic disorders, including pulmonary fibrosis.

PMID- 22661009
TI  - Assessing preferences of beach users for certain aspects of weather and ocean
      conditions: case studies from Australia.
AB  - Three well-known Australian beaches, Surfers Paradise Beach (Gold Coast),
      Narrowneck Beach (Gold Coast) and Bondi Beach (Sydney), were selected for
      analysis of beach user preferences for certain weather and ocean conditions.
      Regression methods were used to determine how the numbers of visitors to these
      beaches are affected by these conditions. Actual visitor numbers were counted at
      three times during the day over several months at each beach with the aid of web
      cameras. The corresponding weather and ocean conditions were obtained from the
      Australian Bureau of Meteorology and local government agencies. Weekly and
      seasonal factors were also considered. The conditions preferred by beach users,
      as found in this study, are: no precipitation, higher temperatures, light-to
      moderate wind speed (less than 30 km/h) and low wave height (up to 1.25 m). This
      study, the first to provide an analysis of beach user preferences for both
      weather and ocean conditions, shows that ocean conditions play a significant role
      in explaining the demand for beach recreation in Australia. It is therefore
      necessary for tourism management authorities or local governments to provide
      accurate and timely weather and ocean information to local, domestic and
      international beach users.

PMID- 22661008
TI  - Advances in understanding the peripheral circadian clocks.
AB  - In the past decade, it has become increasingly evident that the circadian clock
      system plays an important role in many physiological processes. The circadian
      clock can be divided into 2 parts: the central clock, residing in the
      suprachiasmatic nucleus of the hypothalamus, which receives light cues, and the
      peripheral clocks that reside in various tissues throughout the body. The
      peripheral clocks play an integral and unique role in each of their respective
      tissues, driving the circadian expression of specific genes involved in a variety
      of physiological functions. The goal of this review is to provide an introduction
      to and overview of the peripheral clocks, including potential mechanisms,
      targets, and implications for disease states. The peripheral clocks include the
      cardiovascular, metabolic, endocrine, immune, and reproductive systems.

PMID- 22661010
TI  - The zebrafish scale as model to study the bone mineralization process.
AB  - Danio rerio (zebrafish) shows high similarity with humans in terms of bone
      architecture, bone cells, matrix proteins and molecular signalling. The fish body
      is covered by elasmoid scales which are part of the dermal skeleton. Since few
      data have been published about the function of the fish scale cells, we
      investigated the mineralization pattern of the scale and the role of the
      episquamal osteoblasts in the neodeposition of the bone tissue. First, we
      described a specific mineralization pattern and distribution of the bone forming
      cells in different areas of the scale. We observed along the external circuli
      that, during the scale growth, the marginal cells migrate and organize in a cord
      like structure just before the mineralization process takes place generating a
      new circulus. These cells exhibit alkaline phosphatase activity, a well known
      mammalian osteoblastic differentiation marker. The internal circuli are also
      characterized by new matrix deposition. Thus, zebrafish scale represents a useful
      model for analyzing the osteoblast behaviour during bone formation and
      mineralization and it could be useful in physiological studies and
      pharmacological tests.

PMID- 22661012
TI  - On the prevalence and genetic predisposition of monoclonal gammopathy of
      undetermined significance (MGUS).

PMID- 22661013
TI  - Preparation and characterization of a VEGF-Fc fusion protein matrix for enhancing
      HUVEC growth.
AB  - To enhance vascularization of hydrophobic implants in vivo, a VEGF-Fc fusion
      protein consisting of vascular endothelial growth factor (VEGF) fused to the
      immunoglobulin G Fc domain was prepared as an artificial extracellular matrix
      (ECM). VEGF-Fc was stably immobilized on a polystyrene plate due to the
      hydrophobicity of the Fc domain, and significantly enhanced the adhesion of human
      umbilical vein endothelial cells (HUVECs). Additionally, the use of VEGF-Fc as an
      ECM markedly promoted the proliferation of HUVECs longer than 72 h and induced
      the reorganization of actin filaments into larger stress fibers within these
      cells. The VEGF-Fc fusion protein may be a promising artificial ECM for enhancing
      endothelial cell growth.

PMID- 22661011
TI  - Phase II study of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP)
      therapy for newly diagnosed patients with low- and low-intermediate risk,
      aggressive non-Hodgkin's lymphoma: final results of the Japan Clinical Oncology
      Group Study, JCOG9508.
AB  - The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone,
      known as CHOP therapy, has been established as the standard treatment for
      aggressive non-Hodgkin's lymphoma (NHL). Although patients categorized as low (L)
      and low-intermediate (L-I) risk using the International Prognostic Index have
      favorable prognoses in Western countries, the efficacy and safety of CHOP therapy
      has not been prospectively evaluated in Japan. We conducted a phase II study of
      CHOP in L and L-I risk Japanese patients, evaluating overall survival (OS) as the
      primary endpoint. A total of 213 patients were enrolled and treated with eight
      courses of CHOP. Efficacy was evaluated in 168 eligible patients (L risk, 87; L-I
      risk, 81). Five-year OS rates in all eligible, L, and L-I risk patients were 68 %
      [95 % confidence interval (CI): 61-76 %], 73 % (95 % CI: 63-82 %), and 64 % (95 %
      CI: 53-74 %), respectively. The major toxicity observed was grade 4 neutropenia
      (64 %). Grade 4 non-hematological toxicities were observed as follows: one case
      each of paralytic ileus, convulsions, hypoxemia due to interstitial pneumonia,
      and reactivated fulminant hepatitis B. These results show reasonable efficacy and
      safety of the CHOP regimen in Japanese patients with lower risk aggressive NHL
      (UMIN-CTR Number C000000053).

PMID- 22661014
TI  - Sensitivity of dynamic stability to changes in step width during treadmill
      walking by young adults.
AB  - Recent experimental findings support theoretical predictions that across walking
      conditions the motor system chooses foot placement to achieve a constant minimum
      "margin of stability" (MOSmin)--distance between the extrapolated center of mass
      and base of support. For example, while step width varies, similar average MOSmin
      exists between overground and treadmill walking and between overground and
      compliant/irregular surface walking. However, predictions regarding the
      invariance of MOSmin to step-by-step changes in foot placement cannot be verified
      by average values. The purpose of this study was to determine average changes in,
      and the sensitivity of MOSmin to varying step widths during two walking tasks.
      Eight young subjects walked on a dual-belt treadmill before and after receiving
      information that stepping on the physical gap between the belts causes no adverse
      effects. Information decreased step width by 17% (p = .01), whereas MOSmin was
      unaffected (p = .12). Regardless of information, subject-specific regressions
      between step-by-step values of step width and MOSmin explained, on average, only
      5% of the shared variance (beta = 0.11 +/- 0.05). Thus, MOSmin appears to be
      insensitive to changing step width. Accordingly, during treadmill walking, step
      width is chosen to maintain MOSmin. If MOSmin remains insensitive to step width
      across other dynamic tasks, then assessing an individual's stability while
      performing these tasks could help describe the health of the motor system.

PMID- 22661015
TI  - Effect of habitat complexity on richness, abundance and distributional pattern of
      forest birds.
AB  - Structurally complex forests provide more diverse conditions in comparison to
      homogenous forests because of greater variety of microhabitats and trees. This
      study assesses the association of bird species richness, abundance, and
      distributional pattern with habitat complexity (HC) in Kheyrud Forest in the
      north of Iran. Birds were surveyed during spring 2009 by 100 point counts. In
      each point count six habitat features related to the index of HC were computed
      and scored from 0 to 3. Then the scores were summed and divided into two groups
      of low and high complexity, HC <= 6 and HC > 6, respectively. To compare bird
      richness and abundance in different HCs, a two sample t-test was used. Presence
      and absence of bird species at each plot as a dependent variable were compared
      with the vegetation characteristics as an independent variable by means of the
      Canonical Correspondence Analysis. The results revealed bird species richness and
      abundance were significantly higher in more complex habitats. Bird species can be
      divided into two groups, the first group including species which associated with
      late successional stages and the second group, species belonging to early
      successional stages. Numbers of birds belonging to the first group declined in
      less complex forests, whereas the numbers of birds belonging to the second group
      increased. At the stand scale, our results reveal that bird abundance and
      richness are strongly associated with the complexity of vegetation structure in
      the study area.

PMID- 22661016
TI  - Social approval of the community assessment model for odor dispersal: results
      from a citizen survey.
AB  - Odors emitted from US Midwest hog production facilities present farmers,
      residents, and state regulatory agencies with a set of complex challenges. To
      predict odor exposure from multiple swine production sources simultaneously, and
      to determine siting recommendations for proposed new or enlarged hog facilities,
      researchers at Iowa State University designed the community assessment model for
      odor dispersion (CAM). A three-county citizen survey conducted in Iowa examined
      the level of hypothetical social acceptance of the modeling process, and level of
      trust in CAM results. While 69 % of respondents approved of modeling as a way to
      determine the most socially appropriate location for production sites, only 35 %
      would trust the results if potential odor exposure from a new facility were
      proposed to be built near their home. We analyzed approval of the CAM model, and
      level of trust, across a number of demographic, attitudinal, and belief factors
      regarding environmental quality and the hog industry. Overall, trust in CAM was
      uneven and varied across respondents. Those residents who would not trust CAM
      tended to be more concerned with environmental quality and less inclined to
      believe that the hog industry is critically important economically. Those who
      would not trust CAM results also had significantly more direct experience with
      odors. Findings point to predominantly positive, yet equivocal acceptance of CAM
      results among the citizenry, which is not unexpected given conflict typical of
      siting decisions in industry and waste disposal arenas. Recommendations are
      offered regarding the interaction of trust, beliefs and attitudes and the utility
      of CAM.

PMID- 22661017
TI  - Finding space for participation: fisherfolk mobility and co-management of Lake
      Victoria fisheries.
AB  - The literature on fisheries co-management is almost silent on the issue of the
      movement of fisherfolk within fisheries, although such movement must have
      implications for the effectiveness of co-management. The introduction of co
      management often involves the formation of new structures that should enable the
      participation of key stakeholder groups in decision-making and management, but
      such participation is challenging for migrating fishers. The article reports on a
      study on Lake Victoria, East Africa, which investigated the extent of movement
      around the lake and the implications of movement for how fishers participate and
      are represented in co-management, and the implications of the extent and nature
      of movement for co-management structures and processes. The analysis draws on the
      concept of space from the literature on participation in development and on a
      framework of representation in fisheries co-management in addressing these
      questions. The created space is on an 'invited' rather than open basis,
      reflecting the top-down nature of implementation and the desire to secure
      participation of different occupational groups, as well as women in a male
      dominated sector. The more powerful boat owners dominate positions of power
      within the co-management system, particularly as the levels of co-management,
      from sub-district to national, are traversed. The limited power and resources of
      boat crew are exacerbated by the degree and nature of movement around the lake,
      making effective participation in co-management decision-making a challenge.

PMID- 22661018
TI  - Reinforcing the staple line during laparoscopic sleeve gastrectomy: does it have
      advantages? A meta-analysis.
AB  - BACKGROUND: This study aims to identify whether reinforcing the staple line
      during laparoscopic sleeve gastrectomy (LSG) has advantages. METHODS: We searched
      MEDLINE (PubMed; till August 2011), EMBASE (till August 2011), and the Cochrane
      Central Register of Controlled Trials (Central) in the Cochrane Library (till
      August 2011) using common keywords related to sleeve gastrectomy and
      reinforcement. The keywords were as follows: "sleeve gastrectomy" and
      "reinforcement," or "reinforcing," or "reinforce," or "leak," or "leakage," or
      "staple," or "stapling," or "oversew," or "oversewing," or "oversewed." The
      language of publication was limited to English only. RESULTS: Of the 358 articles
      meeting our initial criteria, eight full texts (two randomized control trial
      [RCT] and six cohort studies), involving 1,345 participants (828 patient cases
      and 517 controls) were included in the final analysis. Comparing the
      reinforcement of the staple line to no reinforcement of the staple line, the odds
      ratio (OR) for overall complications was 0.521 (95 % confidence intervals [CI],
      0.349-0.777). In addition, the OR for staple line leak was 0.425 (95 % CI, 0.226
      0.799) and for staple line hemorrhage was 0.559 (95 % CI, 0.247-1.266).
      CONCLUSION: The current study showed that reinforcing the staple line during LSG
      has the following advantages: decreased incidence of postoperative leak and
      overall complications. More prospective studies with better evidence are needed.

PMID- 22661020
TI  - While we wait for a new regulatory framework for surgical mesh.

PMID- 22661019
TI  - Prediction of prostate cancer extracapsular extension with high spatial
      resolution dynamic contrast-enhanced 3-T MRI.
AB  - OBJECTIVES: To assess the value of dynamic contrast-enhanced (DCE) combined with
      T2-weighted (T2W) endorectal coil (ERC) magnetic resonance imaging (MRI) at 3 T
      for determining extracapsular extension (ECE) of prostate cancer. METHODS: In
      this IRB-approved study, ERC 3-T MRI of the prostate was performed in 108
      patients before radical prostatectomy. T2W fast spin-echo and DCE 3D gradient
      echo images were acquired. The interpretations of readers with varied experience
      were analysed. MRI-based staging results were compared with radical prostatectomy
      histology. Descriptive statistics were generated for prediction of ECE and
      staging accuracies were determined by the area under the receiver-operating
      characteristic curve. RESULTS: The overall sensitivity, specificity, positive
      predictive value and negative predictive value for ECE were 75 %, 92 %, 79 % and
      91 %, respectively. Diagnostic accuracy for staging was 86 %, 80 % and 91 % for
      all readers, experienced and less experienced readers, respectively. CONCLUSIONS:
      ERC 3-T MRI of the prostate combining DCE and T2W imaging is an accurate
      pretherapeutic staging tool for assessment of ECE in clinical practice across
      varying levels of reader experience. KEY POINTS : * Endorectal coil (ERC)
      magnetic resonance imaging is widely used for imaging prostatic disease. * ERC 3
      T MRI is reasonably accurate for local prostate cancer staging. * High diagnostic
      accuracy is achievable across different levels of reader experience. * MRI
      facilitates therapeutic decisions in patients with prostate cancer.

PMID- 22661021
TI  - Probable lumbar acute non-compressive nucleus pulposus extrusion in a cat with
      acute onset paraparesis.
AB  - A spinal cord lesion localised caudal to the L6 spinal segment was diagnosed in a
      2-year-old female spayed domestic longhair cat with acute onset paraparesis.
      Magnetic resonance imaging findings were consistent with an acute, non
      compressive nucleus pulposus extrusion of the L5-L6 intervertebral disc. The cat
      was successfully managed with supportive care, including cage confinement.

PMID- 22661022
TI  - A survey of Southeastern United States veterinarians' preferences for managing
      cats with diabetes mellitus.
AB  - This study evaluated primary practitioners' perceptions of managing feline
      diabetics. Surveys distributed during local continuing education events achieved
      a response rate of 46% (90/195). A mean of 74% feline diabetics required chronic
      insulin; 26% were transient diabetics. Choice of insulin was most influenced by
      duration of action: human recombinant protamine zinc insulin was ranked first
      (42%) and glargine second (27%). Dietary management was always/usually
      recommended by 97% respondents, with prescription or proprietary low
      carbohydrate, high-protein diets recommended in 93% responses. More recent
      graduates (P=0.0419), those who worked in larger practices (P=0.0315), and those
      who saw more transient diabetics (P=0.0288) were more likely to recommend dietary
      change. In-house blood glucose curves (BGCs) were the most popular method of
      assessing glycemic control, while at-home BGCs were least popular, although their
      use correlated positively with annual diabetic caseload (r=0.43, P=0.0239).
      Owners mishandling insulin was cited as the most common cause of poor glycemic
      control, while clinical signs of acromegaly were rarely recognized.

PMID- 22661023
TI  - Microbial colonization of the salt deposits in the driest place of the Atacama
      Desert (Chile).
AB  - The Atacama Desert (Chile), one of the most arid places on Earth, shows hostile
      conditions for the development of epilithic microbial communities. In this study,
      we report the association of cyanobacteria (Chroococcidiopsis sp.) and bacteria
      belonging to Actinobacteria and Beta-Gammaproteobacteria and Firmicutes phyla
      inhabiting the near surface of salt (halite) deposits of the Salar Grande Basin,
      Atacama Desert (Chile). The halite deposits were investigated by using optical,
      confocal and field emission scanning electron microscopes, whereas culture
      independent molecular techniques, 16S rDNA clone library, alongside RFLP analysis
      and 16S rRNA gene sequencing were applied to investigate the bacterial diversity.
      These microbial communities are an example of life that has adapted to extreme
      environmental conditions caused by dryness, high irradiation, and metal
      concentrations. Their adaptation is, therefore, important in the investigation of
      the environmental conditions that might be expected for life outside of Earth.

PMID- 22661024
TI  - The 2012 Mark Coventry award: a retrieval analysis of high flexion versus
      posterior-stabilized tibial inserts.
AB  - BACKGROUND: High flexion (HF) implants were introduced to increase ROM and
      patient satisfaction, but design changes to the implant potentially have
      deleterious effects on polyethylene wear. It is unclear whether the HF implants
      affect wear. QUESTIONS/PURPOSES: We therefore examined whether the design changes
      between HF and posterior-stabilized (PS) tibial inserts would affect overall
      damage or damage on their articular surface, backside, and tibial post and
      whether flexion angle achieved related to damage. METHODS: We matched 20
      retrieved HF inserts to 20 retrieved PS inserts from the same implant system on
      the basis of duration of implantation, body mass index, and age. Inserts were
      divided into 16 zones and a microscopic analysis of surface damage was carried
      out. Five inserts were scanned using micro-CT to further quantify instances of
      severe post notching. We determined overall damage with a scoring system.
      RESULTS: We found greater backside and post damage in the HF group but no
      difference in the articular surface or overall damage scores. Backside and post
      damage scores correlated to flexion angle in the HF group. There was no
      flexion/damage correlation in the PS group. Notch depths around the post in both
      groups ranged from 0.6 to 1.9 mm. CONCLUSIONS: HF inserts are more susceptible to
      post damage, possibly as a result of higher contact stresses from greater
      flexion. The increased backside damage was unexpected because the two groups have
      the same tibial component, locking mechanism, and sterilization method. CLINICAL
      RELEVANCE: The introduction of a highly crosslinked HF insert will require close
      scrutiny as a result of the potential for post damage demonstrated in this
      series.

PMID- 22661025
TI  - A gene trap knockout of the Tiam-1 protein results in malformation of the early
      embryonic brain.
AB  - Tiam-1 has been implicated in the development of the central nervous system.
      However, the in vivo function of Tiam-1 has not been fully determined in the
      developing mouse brain. In this study, we generated Tiam-1 knockout mice using a
      Tiam-1 gene-trapped embryonic stem cell line. Insertion of a gene trap vector
      into a genomic site downstream of exon 5 resulted in a mutant allele encoding a
      truncated protein fused with the beta-geo LacZ gene. Primary mouse embryonic
      fibroblasts lacking Tiam-1 revealed a significant decrease in Rac activity and
      cell proliferation. In addition, whole-mount embryonic LacZ expression analysis
      demonstrated that Tiam-1 is specifically expressed in regions of the developing
      brain, such as the caudal telencephalon and rostral diencephalon. More
      importantly, mouse embryos deficient in Tiam-1 gene expression displayed a severe
      defect in embryonic brain development, including neural tube closure defects or a
      dramatic decrease in brain size. These findings suggest that embryonic Tiam-1
      expression plays a critical role during early brain development in mice.

PMID- 22661026
TI  - [Family-centered care and post-traumatic stress disorder].
AB  - A year has passed since a major earthquake and tsunami hit northeastern Honshu,
      Japan in March 2011. Amidst mourning for the tens of thousands of victims,
      survivors have just begun the difficult and urgent tasks of rebuilding. Many
      survivors suffer from post-traumatic stress disorder (PTSD). PTSD causes chronic,
      long-term suffering for patients and their families and inevitably burdens social
      and medical care systems. This article tries to integrate PTSD evidence-based
      treatment experiences into a practical and detailed nursing intervention protocol
      for PTSD. We also elicit the function and effect of "family-centered care." We
      hope that nursing professionals apply family-centered care principles to PTSD
      treatment and care approaches in order to promote PTSD patient resilience. Nurses
      can thus enhance PTSD care efficacy and improve the opportunity for PTSD patients
      to overcome their symptoms and recover their life.

PMID- 22661027
TI  - [The helicopter emergency medical service and essential related nursing skills].
AB  - Nurses play a critical role in Taiwan's helicopter emergency medical service, an
      essential healthcare response service for residents of outlying islands. The care
      skillsets required of nurses in special care and urgent care environments are
      significantly more specialized than those in other professional care
      environments. This article discusses the development of the civil helicopter
      emergency medical service (HEMS) and elements essential to HEMS nursing care
      efficacy. These elements can be grouped under the categories of pre-flight
      preparation, assessment for flight-readiness and in-flight care, decision-making
      abilities, personal physical characteristics, training and experience. These
      categories should be referenced to improve the effectiveness of relevant
      education / training programs, enhance HEMS nurse readiness and effectiveness,
      and maximize the role of HEMS nurses in the civil helicopter medical service.

PMID- 22661028
TI  - [Disaster nursing and primary school teachers' disaster-related healthcare
      knowledge and skills].
AB  - The World Bank has ranked Taiwan as the 5th highest risk country in the world in
      terms of full-spectrum disaster risk. With volatile social, economic, and
      geologic environments and the real threat of typhoons, earthquakes, and nuclear
      disasters, the government has made a public appeal to raise awareness and reduce
      the impact of disasters. Disasters not only devastate property and the ecology,
      but also cause striking and long-lasting impacts on life and health. Thus,
      healthcare preparation and capabilities are critical to reducing their impact.
      Relevant disaster studies indicate children as a particularly vulnerable group
      during a disaster due to elevated risks of physical injury, infectious disease,
      malnutrition, and post-traumatic stress disorder. Primary school teachers are
      frontline educators, responders, and rehabilitators, respectively, prior to,
      during, and after disasters. The disaster prevention project implemented by the
      Taiwan Ministry of Education provides national guidelines for disaster prevention
      and education. However, within these guidelines, the focus of elementary school
      disaster prevention education is on disaster prevention and mitigation. Little
      guidance or focus has been given to disaster nursing response protocols necessary
      to handle issues such as post-disaster infectious diseases, chronic disease
      management, and psychological health and rehabilitation. Disaster nursing can
      strengthen the disaster healthcare response capabilities of school teachers,
      school nurses, and children as well as facilitate effective cooperation among
      communities, disaster relief institutes, and schools. Disaster nursing can also
      provide healthcare knowledge essential to increase disaster awareness,
      preparation, response, and rehabilitation. Implementing proper disaster nursing
      response protocols in Taiwan's education system is critical to enhancing disaster
      preparedness in Taiwan.

PMID- 22661029
TI  - [Roles and functions of military flight nursing: aeromedical evacuation].
AB  - Evacuating the injured is an important part of disaster medicine. Aircraft
      provide timely access to distant and remote areas and, in an emergency, can
      evacuate sick or injured individuals in such areas quickly and safely for
      critical treatment elsewhere. Aeromedical evacuation (AE) comprises the two
      categories of fixed-wing ambulance service and helicopter emergency medical
      service (HEMS). Each aims to accomplish unique objectives. In Taiwan, the Second
      Taiwan Strait Crisis in 1958 established the unique role and functions of medical
      flight nursing. Significant knowledge and experience has been accumulated in the
      field since that time in such areas as the effects of high altitude environments
      on individuals and equipment; physiological, psychological, social and spiritual
      factors that affect the injured and / or response team members; and emergency
      care delivery techniques. All have been essential elements in the development and
      delivery of comprehensive medical flight nurse training. Medical flight nursing
      belongs in a special professional category, as nurses must master knowledge on
      general and special-case casualty evacuation procedures, relevant instruments and
      equipment, triage, in-flight medical care, and aircraft loading requirements
      related to transporting the sick and injured. The internationalization of medical
      care has opened the potential to expand medical flight nursing roles and
      functions into disaster nursing. Although military considerations continue to
      frame medical flight nursing training and preparation today, the authors feel
      that creating strategic alliances with disaster nursing specialists and
      organizations overseas is a future developmental direction for Taiwan's medical
      flight nursing sector worth formal consideration.

PMID- 22661030
TI  - [Traumatic response experiences: one year after Typhoon Morakot].
AB  - BACKGROUND: Disaster-related mental health problems have been a focus of recent
      international scholarly interest. Typhoon Morakot caused exceptional destruction
      in Southern Taiwan, and victims suffered physically, psychologically and
      financially in its aftermath. PURPOSE: This study investigates the post-traumatic
      response and coping behaviors of victims one year after Typhoon Morakot. METHODS:
      Researchers used a phenomenological method with purposive sampling and
      interviewed 10 Typhoon Morakot victims. Data were collected using deep, semi
      structured interviews. All interview sessions were tape-recorded. Researchers
      used Colaizzi's seven-step phenomenological method to analyze data. RESULTS:
      Three common themes emerged in subjects following their disaster experiences. The
      first was residual traumatic response, including fear of continued flooding, fear
      of future flood recurrence, indifference in responses, and living on alert; The
      second was insecurity in daily life due to changed surroundings, including
      anxiety and a heavy sense of loss; The third was conformity in coping behaviors,
      including shifting attention away from the disaster, turning to a pluralistic
      support system, having an optimistic outlook on life, and living in the moment.
      CONCLUSION: Investigating traumatic response experiences and coping behaviors one
      year after the Typhoon Morakot disaster can help guide healthcare professionals
      to promote evidence-based health and nursing services. Findings also provide
      information to healthcare providers essential to improving nursing quality for
      victims of disasters.

PMID- 22661031
TI  - [Difference in predictors of self efficacy and compliance between diabetic and
      non diabetic patients who underwent coronary artery bypass surgery].
AB  - BACKGROUND: Compared to their non-diabetic peers, diabetic patients who undergo
      coronary artery bypass surgery (CABG) face greater complications and poorer
      outcomes. Identifying related risk factors is essential to improving post-CABG
      outcomes in this vulnerable population. Improving self-efficacy and compliance
      can further improve patient outcomes over the long term. PURPOSE: This study
      compared differences in self-efficacy predictors and compliance between diabetic
      and non-diabetic patients who received coronary artery bypass surgery. METHOD: We
      used a cross-sectional design with convenience sampling. A total of 350 patients
      were recruited from two medical centers and one teaching hospital. Instruments
      used included a demographics questionnaire, chronic disease self-efficacy
      questionnaire and compliance scale. SPSS 17.0 for Windows was used to analyze
      data. RESULTS: Results found self-efficacy positively associated with compliance
      in both groups. The non-diabetic group had higher self-efficacy and lower
      compliance than the diabetic group. In the diabetic group, gender, compliance,
      education, employment status and marital status were all predictors of self
      efficacy, with self-efficacy the single predictor of compliance. In the non
      diabetic group, compliance, primary care provider, education, time since surgery,
      gender and exercise were predictors of self-efficacy. Self-efficacy, primary care
      provider, employee status prior surgery were all predictors of compliance.
      CONCLUSIONS: Results provide valuable information regarding the impact of
      diabetes on CABG patient outcomes and differences in predictors of self-efficacy
      and compliance between diabetic and non-diabetic patients. Healthcare providers
      can promote healthy behavior and enhance quality of life by providing patient
      support tailored to their characteristics and considering the factors associated
      with better self-efficacy vs. compliance.

PMID- 22661032
TI  - [The relationship between adolescent body size and health promoting behavior and
      biochemical indicator factors].
AB  - BACKGROUND: Tainan City has the third highest prevalence of junior high school
      student obesity of all administrative districts in Taiwan. School nurses play an
      important role in promoting student health. Understanding the factors that
      significantly impact student weight is critical to designing effective student
      health promotion programs. PURPOSE: This study explored the relationships between
      health promotion behavior and serum biomarker variables and body size. METHODS:
      Researchers used a cross-sectional descriptive study design and stratified
      cluster random sampling. Subjects were 7th graders who received an in-school
      health checkup with blood test at 41 public junior high schools in Tainan City
      between July 2010 and May 2011. Research instruments included the adolescent
      health promotion (AHP) scale, serum biochemical profile and BMI (body mass
      index). Obtained data were analyzed using descriptive and inferential statistics.
      RESULTS: Of the 726 students who participated in this study, 22.2% were
      underweight and 23.8% were overweight or obese. Higher AHP scores correlated with
      better biomarkers and body size. Multivariate analysis found factors that
      increased the risk of being overweight included: being male, having a father with
      a relatively low level of education, playing video games frequently, and doing
      little or no exercise (odds ratio = 1.93, 1.75, 1.07, 1.04, respectively).
      CONCLUSIONS:  IMPLICATIONS FOR PRACTICE: Participants with relatively healthy
      behaviors had better biomarkers and a lower risk of being overweight. Findings
      can support the development of evidence-based school programs to promote student
      health.

PMID- 22661033
TI  - [A study of work stress and professional commitment in outpatient department
      nurses].
AB  - BACKGROUND: Nurses working in outpatient departments face tremendous pressure
      from multiple sources. The effect of nurse professional commitment on continued
      professional development is an issue worth exploring further. PURPOSE: This study
      explored relationships among nurses' personal attributes, work stress and
      professional commitment. METHODS: The Lazarus cognitive appraisal model framed
      the research plan design. Tools used included stress level and professional
      commitment scales for healthcare professionals. Of 180 questionnaires sent to
      outpatient department nurses nurses, 171 (95%) were returned and used in
      analysis. SPSS 12.0 for windows software was used for statistical analysis.
      RESULTS: We found a significant negative correlation between work stress and
      professional commitment and no significant relationship between level of
      education and either ability to handle work stress or professional commitment.
      Years of work experience, age and position all correlated positively with ability
      to handle work stress. Years of work experience correlated positively with
      professional commitment. CONCLUSIONS:  IMPLICATIONS FOR PRACTICE: This study
      suggests that nurses experience the highest work stress levels during their first
      five years of work. Findings show that providing nurses a clear career
      development path, in addition to attractive incentives and a reasonable workload,
      is essential to reducing work stress, bolstering professional commitment and
      increasing retention.

PMID- 22661034
TI  - [A project to reduce the incidence of facial pressure ulcers caused by prolonged
      surgery with prone positioning].
AB  - BACKGROUND & PROBLEMS: We observed in our institute a 13.6% incidence of
      prolonged surgery (>4 hours) induced facial pressure ulcers that required prone
      positioning. Causes identified included: (1) customized silicon face pillows used
      were not suited for every patient; (2) our institute lacked a standard operating
      procedure for prone positioning; (3) our institute lacked a postoperative
      evaluation and audit procedure for facial pressure ulcers. PURPOSE: We designed a
      strategy to reduce post-prolonged surgery facial pressure ulcer incidence
      requiring prone positioning by 50% (i.e., from 13.6% to 6.8%). RESOLUTIONS: We
      implemented the following: (1) Created a new water pillow to relieve facial
      pressure; (2) Implemented continuing education pressure ulcer prevention and
      evaluation; (3) Established protocols on standard care for prone-position
      patients and proper facial pressure ulcer identification; (4) Established a face
      pressure ulcers accident reporting mechanism; and (5) Established an audit
      mechanism facial pressure ulcer cases. RESULTS: After implementing the resolution
      measures, 116 patients underwent prolonged surgery in a prone position (mean
      operating time: 298 mins). None suffered from facial pressure ulcers. The
      measures effectively reduced the incidence of facial pressure ulcers from 13.6%
      to 0.0%. CONCLUSIONS: The project used a water pillow to relieve facial pressure
      and educated staff to recognize and evaluate pressure ulcers. These measures were
      demonstrated effective in reducing the incidence of facial pressure ulcers caused
      by prolonged prone positioning.

PMID- 22661035
TI  - [Reducing fear in preschool children receiving intravenous injections].
AB  - BACKGROUND & PROBLEM: Our pediatric medical ward administers an average of 80
      intravenous injections to preschool children. We found that 91.1% exhibit
      behavior indicative of fear and anxiety. Over three-quarters (77.8%) of this
      number suffer severe fear and actively resist receiving injections. Such behavior
      places a greater than normal burden on human and material resources and often
      gives family members negative impressions that lower their trust in the
      healthcare service while raising nurse-patient tensions. Using observation and
      interviews, we found primary factors in injection fear to be: Past negative
      experiences, lack of adequate prior communication, measures taken to preemptively
      control child resistance, and default cognitive behavioral strategies from
      nursing staff. PURPOSES: This project worked to develop a strategy to reduce
      cases of severe injection fear in preschool children from 77.8% to 38.9% and
      achieve a capacity improvement target for members of 50%. RESOLUTIONS: Our team
      identified several potential strategy solutions from research papers and books
      between August 1st, 2009 and April 30th, 2010. Our proposed method included
      therapeutic games, self-selection of injection position, and cognitive behavioral
      strategies to divert attention. Other measures were also specified as standard
      operating procedures for administering pediatric intravenous injections. RESULT:
      We applied the strategy on 45 preschool children and identified a post-injection
      "severe fear" level of 37.8%. CONCLUSIONS: This project was designed to reduce
      fear in children to make them more accepting of vaccinations and to enhance
      children's positive treatment experience in order to raise nursing care quality.

PMID- 22661036
TI  - [Disaster nursing: one nurse's role and experience during the Fukushima Power
      Plant disaster following the Great East Japan Earthquake].
AB  - The Richter-scale 9.0 earthquake that struck Northeast Japan on March 11th, 2011
      caused a tsunami that damaged the Fukushima No. 1 Power Plant and released
      enormous amounts of radiation into the environment. Many area residents were
      evacuated to several protected fallout shelters. Prior to the tsunami, Fukashima
      had around 505,760 residents over 65 years of age, comprising 24.9% of the city's
      pre-tsunami population of Fukushima (City of Fukushima, 2011). The high
      proportion of elderly contributed to difficulties encountered in evacuating and
      caring for Fukushima citizens in the immediate aftermath of the disaster. The
      first author participated in disaster relief efforts in two fallout shelters in
      Fukushima. This article was written to share her post-disaster care experience
      and learned knowledge with medical care professionals in Taiwan and other high
      earthquake risk areas. The article also offers guidelines on appropriate medical
      personnel response and behavior with regard to disaster response. We hope this
      experience-sharing offers positive suggestions for the future and facilitates
      improved disaster-care education in East Asia and enhanced international
      cooperation on disaster rescue.

PMID- 22661037
TI  - [Compassion fatigue and coping strategies for hospital nurses].
AB  - Over-involvement in patient trauma and loss in clinical settings negatively
      affects nurses and may cause compassion fatigue. Compassion fatigue is associated
      with prolonged exposure to trauma cases, over-involvement in patient situations
      and over-extending caring energies. Nurses unable to adapt and cope may suffer
      physically and psychologically, reduce their quality of care, cause medical care
      costs to increase, and ultimately become frustrated and decide to leave the
      nursing profession. While current approaches to addressing compassion fatigue
      focus on evaluating individual nurse situations, adjusting attitudes, holding
      education programs, and bolstering support systems, little research attention has
      been directed toward the consequences of such on patient care or the origins of
      compassion fatigue in Taiwan nurses. This paper defines compassion fatigue,
      examines its importance and consequences, and delineates common nursing coping
      strategies in Taiwan. Findings expand domestic research on this phenomenon and
      suggest relevant theories and effective interventions to achieve remediation.

PMID- 22661038
TI  - [An introduction to contextual family nursing therapy].
AB  - The author has extensive experience interacting with families in clinical
      settings, clinical competency, multidisciplinary collaboration experience, and
      experience exploring the development of the nursing role. I used four research
      steps to integrate several decades of research experience and findings in order
      to propose a theoretical framework and practical therapeutic competency. I hope
      this introduction offers insights to hardworking nurses and helps them address
      the many possible family situations that could arise in clinical settings.

PMID- 22661039
TI  - [Feeding preterm infants: application of developmental care].
AB  - Developmental care is the core concept of the preterm infant caring model. It is
      characterized by interaction, individualization, and evolving process. In order
      to enhance family competency with regard to preterm infant care, health
      professionals should include parents as team members when preterm infants are
      hospitalized so that parents can provide care helpful to facilitate preterm
      infant adaptation to external environmental stimulation. The preterm infant's 6-8
      feedings per day represent the most frequent daily activity and an activity in
      which safety is essential. Potential adverse feeding responses in preterm infants
      such as tachypnea, cyanosis, and fatigue may stress the mother. This is a
      particular risk when the mother tries to increase her infant's intake volume by
      over-stimulating oral-motor activity. Theories and guidelines for feeding preterm
      infants in western societies have been evolving since the 1980s. However, little
      has been done in this area in Taiwan. This article addresses preterm infant
      feeding characteristics and cues, the application of developmental care in
      feeding infants, and proposes guidelines for feeding preterm infants. Healthcare
      professionals may reference our suggestions in feeding preterm infants and
      educating parents.

PMID- 22661040
TI  - [An experience applying a spiritual care model to a first-time stroke patient].
AB  - Patients with stroke-related disabilities are at risk of depression and social
      isolation. This can make it difficult for the patient to cope with his or her
      disease and increase caregiver burden. While good at dealing with physical
      illness, nurses are often poor at attending to patients' mental and spiritual
      needs. In this paper, the authors introduce their experience using a spiritual
      care model to care for a stroke patient. The patient, a 69 year-old retiree, was
      admitted to our hospital due to an acute stroke. During hospitalization, he
      suffered from acute confusion and persistent focal weakness. His disability
      resulted in physical dependence, which did not improve during rehabilitation. We
      used a model of spiritual care and in-depth evaluation to identify several
      underlying psychological issues. These included feelings of hopelessness and loss
      of control and motivation. The authors established trust through active
      listening. In addition to standard nursing education and physical care, we, in
      cooperation with the patient's children, provided encouragement and support to
      help the patient cope with his disease burden and actively participate in
      rehabilitation. We applied a multi-dimensional spiritual care approach to help
      the patient shift from hopelessness to hopefulness. This enhanced his motivation
      to participate in rehabilitation and improved his self-care abilities. We hope
      this case report on the application of a spiritual-care model is useful reference
      for nurses responsible to care for stroke patients.

PMID- 22661041
TI  - Acute injuries and overuse syndromes in sport climbing and bouldering in Austria:
      a descriptive epidemiological study.
AB  - BACKGROUND: The increasing popularity of climbing activities is associated with a
      rise in the number of respective injuries and overuse syndromes. However, a
      comprehensive scrutiny of the incidence, kind and severity of climbing-related
      ailments in Austria is so far outstanding. We aimed to evaluate injuries and
      overuse syndromes in sport climbing and bouldering in Austria and to investigate
      whether the injury incidence differs between specific groups of climbers. DESIGN:
      Retrospective cross-sectional self-report study. METHODS: A self-report
      questionnaire to assess (a) demographic and anthropometric characteristics, (b)
      climbing experience and skill level, and (c) detailed information on climbing
      related injuries was made available in climbing halls and on the Internet. Data
      from 193 climbers (133 males and 60 females; age 30.4 +/- 8.1 years; average
      climbing experience 9.3 +/- 7.7 years) were acquired. RESULTS: A total of 374
      injuries were reported by 130 participants (67.4 %). The single most common
      differential diagnoses, accounting for 56.7 % of all injuries, were strains and
      ruptures of annular ligaments of the fingers, lateral epicondylitis of the elbow,
      and sprains or fractures of the ankle joint. The odds for strains of the annular
      ligaments and lateral epicondylitis were greater in men and increased with older
      age and higher exposure to climbing stress. CONCLUSIONS: This is the first
      comprehensive study investigating climbing-related injuries in Austria. The
      incidence and kind of the ailments reported confirm results of previous studies.
      Moreover, our results suggest that the risk to suffer climbing-related overuse
      syndromes, but not acute injuries, is dependent on sex, age, and exposure to
      climbing stress.

PMID- 22661042
TI  - Treatment with aspirin, NSAID, corticosteroids, and colchicine in acute and
      recurrent pericarditis.
AB  - Empiric anti-inflammatory therapy for acute and recurrent pericarditis is
      warranted for viral and idiopathic cases that represent most cases of
      pericarditis in developed countries. For specific uncomplicated etiologies, such
      as systemic autoimmune diseases and postpericardiotomy syndromes, the same drugs
      are also indicated. Aspirin and non-steroidal anti-inflammatory drugs (NSAID) are
      mainstay of therapy with the possible adjunct of colchicine, especially for
      recurrences. Corticosteroids are a second choice for difficult cases requiring
      multi-drug therapies and specific medical conditions (i.e., specific cases with
      systemic autoimmune diseases, postpericardiotomy syndrome, and pregnancy).
      Medical therapy of pericarditis should be individualized as much as possible
      providing the attack dose every 8 h to ensure full daily control of symptoms and
      till remission and C-reactive protein normalization, and then tapering should be
      considered. The present paper will review current evidence for the treatment of
      acute and recurrent pericarditis with aspirin, NSAID, corticosteroids, and
      colchicine.

PMID- 22661043
TI  - Isolation and functional analysis of Thmfs1, the first major facilitator
      superfamily transporter from the biocontrol fungus Trichoderma harzianum.
AB  - A novel major facilitator superfamily (MFS) transporter gene, Thmfs1, was
      isolated from Trichoderma harzianum (T. harzianum). A Thmfs1 over-expressing
      mutant displayed enhanced antifungal activity and fungicide tolerance, while the
      Thmfs1 disruption mutant showed the opposite trend. Trichodermin production in
      Thmfs1 disruption group (185 mg l(-1)) was decreased by less than 17 % compared
      to the parental strain, suggesting that Thmfs1 is not mainly responsible for
      trichodermin secretion. Real-time PCR showed that Thmfs1 transcript level could
      be induced by a certain range of trichodermin concentrations, while expression of
      Tri5, encoding a trichodiene synthase, was strongly inhibited under these
      conditions. To our knowledge, Thmfs1 is the first MFS transporter gene identified
      in T. harzianum.

PMID- 22661044
TI  - Acute myeloid leukemia with t(7;21)(q11.2;q22) expresses a novel, reversed
      sequence RUNX1-DTX2 chimera.
AB  - The RUNX1 gene is frequently rearranged in acute leukemia. We cloned a novel
      RUNX1 chimeric gene generated by t(7;21)(q11.2;q22) in a patient with acute
      myeloid leukemia. 3'-rapid amplification of cDNA ends analysis showed a tail-to
      tail fusion between RUNX1 on 21q22 and DTX2 on 7q11.2, with an insertion of short
      complementary sequence from UPK3B adjacent to DTX2. DTX2 encodes a putative E3
      ubiquitin ligase with no known biological function. There are two possible
      functions of RUNX1-reversed UPK3B-DTX2: one from aberrant RUNX1 chimeric protein
      and the other from the reversed sequence of DTX2. The predicted aberrant protein
      expressed under the RUNX1 promoter was highly structurally similar to RUNX1a. In
      a reporter assay, the aberrant protein inhibited the trans-activation function of
      RUNX1 in a dominant-negative manner, similar to RUNX1a. In contrast, the DTX2
      reversed sequence may degrade wild-type DTX2 transcript or suppress its
      translation. In conclusion, we identified a novel fusion RUNX1 partner, DTX2,
      which chimerize in a reverse direction. This is the first example of RUNX1
      chimera in an opposing direction generated by chromosomal translocation in
      leukemia. In addition to the aberrantly truncated RUNX1 protein, the DTX2
      antisense sequence may play some role in the development of leukemia carrying the
      t(7;21) translocation.

PMID- 22661046
TI  - "I didn't see this coming.": why are postbariatric patients in substance abuse
      treatment? Patients' perceptions of etiology and future recommendations.
AB  - BACKGROUND: Recent evidence suggests that bariatric patients may be
      overrepresented in inpatient substance abuse treatment, but the reasons for this
      are unclear. Patients' perceptions of this problem may be of heuristic value.
      Using a qualitative approach, the present study evaluated bariatric patients'
      impressions of how their postsurgical substance use disorders emerged and their
      future recommendations for those working with bariatric patients. METHODS: Semi
      structured interviews were conducted with 24 bariatric patients in an inpatient
      substance abuse treatment program. Seven prominent themes emerged, four referring
      to etiology of substance use (unresolved psychological problems, addiction
      transfer/substitution, faster onset or stronger effects from substances, and
      increased availability of pain medications) and three pertaining to future
      recommendations (counseling pre- and/or postsurgery, increased knowledge of the
      associated risks of substance use postsurgery, and greater "honesty"). Blind
      coders rated the presence or absence of each theme in each interview. RESULTS: Of
      the four etiology themes, 75 % of patients acknowledged unresolved psychological
      problems, 83.33 % identified addiction transfer/substitution, 58.33 % noticed
      faster onset or stronger effects from substances, and 45.83 % identified
      increased availability of pain medications. For future recommendations, 41.67 %
      suggested counseling pre- and/or postsurgery, 70.83 % suggested increased
      education about the associated risks of substance use postsurgery, and 41.67 %
      identified a need for greater "honesty." CONCLUSIONS: Patient perceptions suggest
      that several common themes may be related to risk for the development of
      postsurgical substance use disorders.

PMID- 22661047
TI  - Comparison of four reconstructive methods for diaphyseal defects of the humerus
      after tumor resection.
AB  - The objective of the current study was to compare quantitative data on the
      biomechanical analysis of different techniques for fixation of intercalary bone
      defects of the humerus, by means of consistently applied methodology on composite
      models. A total of 25 humeral specimens of composite models were used. An
      intercalary defect was created and reconstructed using plates, intramedullary
      nails, external fixators and segmental prosthetic implants. The specimens were
      loaded under axial compression, four-point bending and torsion within the linear
      elastic region. Modular segmental implants and intramedullary nails were able to
      compensate significantly greater amounts of compressive loads compared to locking
      plates and external fixators. However, in flexion and torsion, the modular
      segmental implants and the external fixators were significantly better load
      bearing devices compared to the intramedullary nails and plates. Early
      mobilization of the upper limb in patients with diaphyseal bone defects of the
      humerus could probably be more safe and tolerable when reconstructed with modular
      segmental implants.

PMID- 22661045
TI  - Biological therapy and the immune system in patients with chronic myeloid
      leukemia.
AB  - Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of
      hematopoietic stem cells that has been recognized as a disease responsive to
      immunotherapy. Despite the huge success of the tyrosine kinase inhibitors (TKIs),
      CML remains for the most part incurable, probably due to treatment resistance of
      leukemic stem cells, which are responsible for rapid disease relapse after
      discontinuation of therapy. Only allogeneic stem cell transplantation enables
      disease eradication. In addition to the Bcr-Abl1 oncoprotein, TKIs also inhibit
      off-target kinases (e.g. c-kit, Src, Tec), some of them having physiological
      functions in immune responses. In vitro studies have implied immunomodulatory
      effects of TKIs and interferon-alpha (IFN-alpha), but comprehensive information
      from in vivo analyses is missing. This review summarizes the recent advances in
      the field of immunology of CML, including basic information about leukemia
      associated antigens and peptide vaccines, that could lead to the incorporation of
      TKIs and IFN-alpha in future therapeutic, potentially curative, interventions for
      CML.

PMID- 22661048
TI  - Regional trends in obesity and overweight among Austrian adults between 1973 and
      2007.
AB  - This paper examines regional changes in the prevalence of overweight (BMI >= 25
      kg/m2) and obesity (BMI >= 30 kg/m2) among Austrian adults (aged >= 20 years)
      during a 35-year period, taking into account the social inequality with regard to
      obesity. Self-reported data from five cross-sectional nationally representative
      surveys (n = 178,818) conducted between 1973 and 2007 were analysed. The
      prevalence of overweight was higher in men than women (2007: 46.3 vs. 31.2 %;p <
      0.001) and similar in all Austrian regions. There was a clear east-west gradient
      for obesity among both sexes, with the highest rates in Eastern Austria (in 2007,
      women: 18.1 %, men: 16.1 %;p < 0.001) and the lowest in Western Austria (in 2007,
      women: 12.6 %, men: 11.7 %;p < 0.001). Logistic regression analyses have shown a
      general decrease of overweight per year among women (OR = 0.991, 95 % CI 0.990
      0.993) and men (OR = 0.999, 95 % CI 0.998-1.000), while the obesity prevalence
      has risen during the study period in every region (women: OR = 1.003, 95 % CI
      1.001-1.005; men: OR = 1.011, 95 % CI 1.009-1.013), with the highest increase
      among women in Central Austria and men in Western Austria. Social inequalities
      for obesity showed a tendency to increase in the Western and Eastern region. Our
      results showed a significant regional difference for obesity prevalence during
      the entire study period. Obesity is a frequent health problem among Austrian
      adults residing in the Eastern region.

PMID- 22661049
TI  - Study of factors for unsuitability of DSAEK in cases of corneal decompensation
      following cataract surgery.
AB  - To evaluate suitability of Descemet's stripping automated endothelial
      keratoplasty (DSAEK) in cases of corneal decompensation following cataract
      surgery. In this cross-sectional case series, 90 eyes of 90 patients were
      evaluated at a tertiary eye care centre. Cases with central corneal scarring or
      vascularisation, complicated aphakia with significant iris tissue defects and
      extensive synechaie or posterior segment pathology precluding visual recovery
      were classified as unsuitable for DSAEK. Of 90 eyes, 42 (46.67%) were unsuitable
      for DSAEK. Multivariate logistic regression analysis, revealed that patients
      presenting more than a year after cataract surgery had 7.5-fold odds of being
      unsuitable for DSAEK as compared with those who presented earlier(OR 7.5; CI 2.0
      29.1). Patients with BCVA poorer than 0.06 at initial presentation had 5.0 times
      odds of being unsuitable for DSAEK (OR 5.0; CI 1.0-24.2). Patients who had prior
      non-phacoemulsification cataract surgery were 5.5 times less likely to be
      candidates for DSAEK as compared to those who had prior phacoemulsification (OR
      5.5; CI 1.5-19.9) and those with anterior chamber IOL or aphakia were 5.0 times
      less likely suitable for DSAEK, in contrast to posterior chamber intraocular
      lenses (OR 5.0; CI 1.3-18.7). The type of cataract surgery, time to presentation
      and initial visual acuity play a role in determining the suitability of
      performing DSAEK in patients with corneal decompensation after cataract surgery.

PMID- 22661050
TI  - Uveitis with occult choroiditis due to Mycobacterium kansasii: limitations of
      interferon-gamma release assay (IGRA) tests (case report and mini-review on
      ocular non-tuberculous mycobacteria and IGRA cross-reactivity).
AB  - Ocular tuberculosis is difficult to diagnose but should be suspected when uveitis
      fails to respond to inflammation suppressive therapy. Interferon-gamma release
      assays (IGRAs) represent a substantial help to diagnose suspected ocular
      tuberculosis especially in non-endemic areas. Indocyanine green angiography
      (ICGA) is able to detect clinically silent choroiditis that, when associated with
      a positive IGRA test, should lead the clinician to suspect ocular tuberculosis,
      warranting specific therapy. The fact that IGRA tests can also react with some
      atypical strains of mycobacteria is not always known. We report here a case with
      resistant post-operative inflammation that presented with occult ICGA-detected
      choroiditis and a positive IGRA test that was most probably due to the non
      tuberculous mycobacterium (NTM) Mycobacterium kansasii. A 66 year-old man
      presented with a resistant cystoid macular oedema (CMO) in his left eye after
      combined cataract and epiretinal membrane surgery. At entry, his best-corrected
      visual acuity (BCVA) was 0.5 for far and near OS. Intraocular inflammation
      measured by laser flare photometry was elevated in the left eye (54.4 ph/ms) and
      also in the right eye (50.9 ph/ms). Four subTenon's injections of 40 mg of
      triamcinolone did not produce any substantial improvement. Therefore a complete
      uveitis work-up was performed. Fluorescein angiography showed CMO OS and ICGA
      showed numerous hypofluorescent dots and fuzziness of choroidal vessels in both
      eyes. Among performed laboratory tests, the QuantiFERON(r)-TB Gold test was
      positive. After a pulmonological examination disclosing a right upper lobe
      infiltrate, the patient was started on a triple anti-tuberculous therapy.
      Bronchial aspirate, obtained during bronchoscopy, was Ziehl-positive and culture
      grew M. kansasii. Nine months later, BCVA OS increased to 1.0 and flare decreased
      to 40.2 ph/ms. The CMO OS resolved angiographically and did not recur with a
      macula still slightly thickened on OCT. Suspected ocular tuberculosis based on
      clinical findings and a positive IGRA test can, in rare instances, be due to
      atypical mycobacteria that also produce positive IGRA tests such as M. kansasii,
      M. szulgai, M. gordonae, M. flavescens and M. marinum. In our case failure to
      isolate the atypical mycobacterium would not have had negative therapeutic
      consequences, as M. kansasii is sensitive to the standard anti-tuberculous
      treatments, which is not the case with other NTMs.

PMID- 22661051
TI  - Do hip OA patients referred to orthopedic surgeons by general practitioners and
      rheumatologists differ?
AB  - There is no consensus regarding indications for total hip arthroplasty (THA) in
      hip osteoarthritis (OA). Patients can be referred to surgeons either by a general
      practitioner (GP) or a rheumatologist. The aim of this study was to determine
      whether patients referred to orthopedic surgeons by GP and rheumatologists
      differed. GPs and rheumatologists were asked to include one patient suffering
      from hip OA for whom a consultation with a surgeon was planned to determine if
      THA was indicated. Surgeons' decisions were obtained by follow-up questionnaires.
      Univariate and then multivariate statistical analysis evaluated differences
      between patients referred by GPs and those referred by rheumatologists. A total
      of 558 patients were included. THA was prescribed in 71.6 % of patients referred
      by rheumatologists vs. 57.6 % of patients referred by GPs (p = 0.008). Patients
      referred by rheumatologists were younger (66.3 vs. 69.3 years; p = 0.006), less
      frequently retired (72.9 vs. 84.2 %; p = 0.007), and presented with a higher New
      Zealand score (54.3 vs. 48.1; p = 0.0009). On multivariate analysis, the
      variables related to patients referred by rheumatologists were the SF-12 mental
      score, the New Zealand score, and the surgeon's decision. Patients consulting a
      surgeon to discuss THA were more likely to be operated on when referred by a
      rheumatologist, which might be due to differences in the rheumatologists' and
      GPs' opinions on the right time to perform surgery or due to differences in the
      populations followed by rheumatologists and GPs, those followed by
      rheumatologists being younger, more active, more urban, with a greater
      willingness to undergo surgery.

PMID- 22661052
TI  - Ultrasonographic resolution of the vessel wall oedema with modest clinical
      improvement in a large-vessel vasculitis patient treated with tocilizumab.
AB  - We report a 63-year-old man with large-vessel giant cell arteritis with affection
      of the aorta in its thoracal descendens and abdominal segments, both axillar
      arteries and the left carotid artery. The diagnosis was confirmed with positive
      biopsy of the temporal artery. The patient was treated with prednisolone at first
      and thereafter with methotrexate. Due to a moderate clinical response,
      tocilizumab at a dose of 8 mg/kg was added 8 weeks after diagnosis. The patient
      did not improve clinically, and the prednisolone dose could not be tapered
      rapidly as previously reported in small case series. Nevertheless, the wall
      oedema determined by ultrasonography in both axillar and left carotid arteries
      almost disappeared 2 months after tocilizumab initiation. Two months after the
      last tocilizumab, the patient relapsed clinically. Tocilizumab seems to be an
      effective therapy with faster resolution of the vessel wall oedema determined by
      ultrasonography by suppressing Th17-cell activity. But the clinical improvement
      in our patient has been moderate and short-lived due to persistent Th1 cells
      activity.

PMID- 22661053
TI  - Association of hypermobility and ingrown nails.
AB  - Ingrown nail (onychocryptosis) is a common condition with severe pain and various
      associated morbidities. Although some underlying factors are identified, its
      etiology remains largely unknown. Generalized joint hypermobility (GJH) is a
      common entity with clinical features that might prone affected individuals to
      ingrown nails. Herein, we investigated the incidence of GJH in patients with
      ingrown nails to determine possible association between hypermobility and ingrown
      nail formation. Patients 16-50 years of age who were undergoing treatment for
      ingrown nails at the dermatology clinic were consecutively enrolled into the
      study. Patients with known rheumatic diseases or orthopedic foot disorders were
      excluded. All patients were in a pain-free period at the time of examination. The
      control group was comprised of age- and sex-matched healthy subjects without a
      history of ingrown nail. Assessment of GJH was made according to Beighton
      criteria. Local hypermobility was evaluated by measurement of range of motion
      using a goniometer. Thirty-nine patients (male/female, 17/22, mean age 31.9 +/-
      11.3 years) and 32 healthy subjects (male/female 12/20, mean age 31.7 +/- 10.4
      years) were included. Patients with ingrown toe nails were more likely to have
      GJH compared to healthy subjects (35.9 vs. 9.4 %, p = 0.009). Toes with ingrown
      nails had significantly smaller maximum dorsiflexion angles (p < 0.001) compared
      to toes of healthy subjects. Ingrown nail formation may be associated with GJH.
      However, when examined locally, there is a limited range of motion in the
      affected toe rather than hypermobility, which could be due to the degenerative
      process facilitated by the hypermobility.

PMID- 22661054
TI  - Long-term cycles of hypoxia and normoxia increase the contents of liver
      mitochondrial DNA in rats.
AB  - The mitochondrion is an important cellular component responsible for regulating
      energy, oxidative metabolism, and acclimatization to high altitude. This study is
      aimed at investigating the impact of long-term exposure to hypoxia on the amount
      of mitochondrial DNA (mtDNA) in rat livers. Male Sprague-Dawley rats were
      randomized and exposed to normoxia (group I), or 5,000 m (barometric pressure
      about 405.35 mmHg) above the sea level (a hypoxic condition) for 23 and 1 h
      normoxia daily for five consecutive days (group II), 15 days (group III), and 30
      days (group IV), respectively. The levels of plasma malondialdehyde (MDA),
      homocysteine (Hcy), superoxide dismutase (SOD), and alanine aminotransferase
      (ALT), the contents of liver mtDNA, mitochondrial transcription factor A (mtTFA),
      cytochrome oxidase 1 (COX1), COX2, and COX3 mRNA transcripts, and mitochondrial
      respiratory activity were examined immediately after the last cycle. In
      comparison with that in control rats, 5-15 cycles of hypoxia/normoxia
      significantly increased the levels of plasma MDA and ALT, but reduced the levels
      of Hcy and SOD, accompanied by impairing liver respiratory function in rats. Long
      term (30) cycles of hypoxia/normoxia reduced the levels of plasma MDA and ALT,
      but increased the levels of SOD and Hcy, accompanied by decreased mtTFA
      expression and mtDNA amount, improved mitochondrial respiratory function in rat
      liver, when compared that of 5-15 cycles of hypoxia/normoxia. Our data indicate
      that long-term cycles of hypoxia/normoxia increases the amount of mtDNA and up
      regulates COX expression, contributing to acclimatization to very high altitude
      in rats.

PMID- 22661055
TI  - Prospective ECG-gated 320-row CT angiography of the whole aorta and coronary
      arteries.
AB  - OBJECTIVES: To investigate the feasibility of using a prospective ECG-gated wide
      volume protocol in CT angiography (CTA) of the whole aorta and coronary arteries
      (CA). METHODS: A total of 61 consecutive patients with suspected acute aortic
      diseases underwent CTA of the whole aorta using a prospective ECG-gated wide
      volume CT protocol without heart rate (HR) control. The exposure window was set
      at 40-50 % of R-R interval (HR >=70 bpm) or 70-80 % of R-R interval (HR <70 bpm)
      in a single heartbeat. The image quality of the ascending aorta, aortic valve and
      CA was evaluated for motion artefacts. The mean attenuation was measured at
      different levels of the aorta. The radiation dose and contrast medium volume were
      recorded. RESULTS: All of the examinations were performed successfully. The image
      quality was acceptable in the ascending aorta, aortic valve (100 %) and CA (94.4
      %). The mean radiation dose was 18.42 +/- 5.02 mSv. Of 61 patients, 14 were
      diagnosed with aortic aneurysm and 35 were diagnosed with aortic dissection or
      intramural haematoma. Coronary artery stenosis was detected in 12 patients.
      CONCLUSION: For patients with aortic diseases, CTA of the whole aorta using a
      prospective ECG-gated wide-volume protocol has the potential to provide
      additional information about the CA and aortic valve with lower radiation
      exposure. KEY POINTS : * Computed tomography is increasingly used to assess the
      coronary arteries and the aorta. * This novel study investigates prospective ECG
      gated wide-volume 320-row CT angiography. * Heart rate variation did not
      influence the image quality of coronary arteries. * Abnormalities in the coronary
      arteries and aorta can be simultaneously assessed noninvasively.

PMID- 22661056
TI  - Differential diagnosis of sclerosing cholangitis with autoimmune pancreatitis and
      periductal infiltrating cancer in the common bile duct at dynamic CT, endoscopic
      retrograde cholangiography and MR cholangiography.
AB  - OBJECTIVES: To compare findings at dynamic computed tomography (CT), endoscopic
      retrograde cholangiography (ERC) and magnetic resonance cholangiography (MRC) in
      patients with sclerosing cholangitis with autoimmune pancreatitis (SC-AIP) and
      periductal infiltrating cancer in the common bile duct (CBD), and to evaluate the
      diagnostic performance of ERC and MRC in differentiating between the two
      diseases. METHODS: Bile duct changes at dynamic CT, ERC and MRC were compared in
      58 patients with SC-AIP and CBD involvement and 93 patients with periductal
      infiltrating CBD cancer. Two radiologists rated their confidence in
      differentiating between the two diseases and the diagnostic performances of ERC
      and MRC were compared. RESULTS: At CT, SC-AIP was more frequently associated with
      intrapancreatic CBD involvement, thinner CBD walls, concentric wall thickening,
      smooth outer margins, and lower degrees of upstream ductal dilatation and
      contrast enhancement (P <= 0.05) than CBD cancer. At ERC and MRC, SC-AIP was more
      frequently associated with smooth margins, gradual and symmetric narrowing,
      multifocal involvement and hourglass appearance (P <= 0.027) than CBD cancer. MRC
      showed good diagnostic performance comparable to ERC. CONCLUSIONS: Dynamic CT,
      ERC and MRC can be helpful in distinguishing SC-AIP from periductal infiltrating
      CBD cancer. MRC may be a useful diagnostic alternative to ERC in differentiating
      between the two diseases. KEY POINTS : * SC-AIP often mimics periductal
      infiltrating ductal cancer. * Imaging findings of SC-AIP and periductal
      infiltrating CBD cancer can be similar. * Dynamic CT, ERC and MRC help
      differentiate between these two diseases. * MRC may be a useful diagnostic
      alternative to ERC.

PMID- 22661057
TI  - Quantified terminal ileal motility during MR enterography as a potential
      biomarker of Crohn's disease activity: a preliminary study.
AB  - OBJECTIVE: To compare quantified terminal ileal (TI) motility during MR
      enterography (MRE) with histopathological severity of acute inflammation in
      Crohn's disease. METHODS: A total of 28 Crohn's patients underwent MRE and
      endoscopic TI biopsy. Axial and coronal TrueFISP, HASTE and post-gadolinium VIBE
      images were supplemented by multiple coronal TrueFISP cine motility sequences
      through the small bowel volume. TI motility index (MI) was quantified using
      validated software; an acute inflammation score (eAIS; 0-6) was assigned to the
      biopsy. Two observers qualitatively scored mural thickness, T2 signal, contrast
      enhancement and perimural oedema (0-3) to produce an activity score (aMRIs) based
      on anatomical MRI. The association among the MI, eAIS and aMRIs was tested using
      Spearman's rank correlation. Wilcoxon rank sum test compared motility in subjects
      with and without histopathological inflammation. RESULTS: Mean MI and mean eAIS
      were 0.27 (range 0.06-0.55) and 1.5 (range 0-5), respectively. There was a
      significant difference in MI between non-inflamed (mean 0.37, range 0.13-0.55)
      and inflamed (mean 0.19, range 0.06-0.44) TI, P = 0.002, and a significant
      negative correlation between MI and both eAIS (Rho = -0.52, P = 0.005) and aMRIs
      (R = -0.7, P < 0.001). CONCLUSION: Quantified TI motility negatively correlates
      with histopathological measures of disease activity and existing anatomical MRI
      activity biomarkers. KEY POINTS: * Magnetic resonance imaging is increasingly
      used to assess Crohn's disease. * MRI measurements can provide a quantitative
      assessment of small bowel motility. * MR enterography can grade Crohn's disease.
      * Small bowel motility can be used as a marker of inflammatory activity.

PMID- 22661058
TI  - PET/CT in lung cancer: Influence of contrast medium on quantitative and clinical
      assessment.
AB  - OBJECTIVES: To evaluate the influence of intravenous contrast medium and
      different contrast medium phases on attenuation correction, PET image quality and
      clinical staging in combined PET/CT in patients with a suspicion of lung cancer.
      METHODS: Sixty patients with a suspicion of lung cancer were prospectively
      enrolled for combined (18)F-FDG-PET/CT examination. PET images were reconstructed
      with non-enhanced and arterial and venous phase contrast CT. Maximum and mean
      standardised uptake values (SUVmax and SUVmean) and contrast enhancement (HU)
      were determined in the subclavian vein, ascending aorta, abdominal aorta,
      inferior vena cava, portal vein, liver and kidney and lung tumour. PET data were
      evaluated visually for clinical staging and image quality. RESULTS: SUVmax was
      significantly increased between contrast and non-contrast PET/CT at all anatomic
      sites (all P < 0.001). SUVmax was significantly increased for arterial PET/CT
      compared to venous PET/CT in the arteries (all P < 0.001). Venous PET/CT resulted
      in significantly higher SUVmax values compared to arterial PET/CT in the
      parenchymatous organs (all P < 0.05). Visual clinical evaluation of malignant
      lesions showed no differences between contrast and non-contrast PET/CT (P = 1.0).
      CONCLUSIONS: Contrast enhanced CT is suitable for attenuation correction in
      combined PET/CT in lung cancer; it affects neither the clinical assessment nor
      image quality of the PET images. KEY POINTS : * Positron emission tomography
      combined with computed tomography is now a mainstream investigation * There has
      been debate about whether CT contrast agents affect PET results * Contrast
      enhanced CT is satisfactory for attenuation correction in lung cancer PET/CT *
      Multiphase CT does not affect PET; additional unenhanced CT is unnecessary * For
      quantitative follow-up PET analysis, an identical PET/CT protocol is required.

PMID- 22661059
TI  - Explanations pertaining to the hip joint flexor moment during the stance phase of
      human walking.
AB  - A hip joint flexor moment in the last half of the stance phase during walking has
      repeatedly been reported. However, the purpose of this moment remains uncertain
      and it is unknown how it is generated. Nine male subjects were instructed to walk
      at 4.5 km/h with their upper body in three different positions: normal, inclined
      and reclined. Net joint moments were calculated about the hip, knee and ankle
      joint. The peak hip joint flexor moment during late stance was significantly
      lower during inclined walking than in the two other conditions. During normal
      walking the iliacus muscle showed no or very weak activity and first at the
      transition from stance to swing. When walking reclined, a clear but rather low
      activity level of the iliacus muscle was seen in the first half of the stance
      phase, which could contribute to the hip moment. In the inclined condition the
      iliacus showed much increased activity but only in the swing phase. It is
      concluded that the hip flexor moment in question is largely generated by passive
      structures in the form of ligaments resisting hip joint extension.

PMID- 22661060
TI  - Mosaic structure of the small cryptic plasmid pKST23 from Escherichia coli.
AB  - Small plasmid pKST23 was isolated from sheep ruminal Escherichia coli population.
      Plasmid sequence was determined to be 2,779 bp in length and was found to have an
      overall 42 % of GC pairs. However, its sequence can be divided into two regions
      based on genetic composition and the GC content. It was found that the high GC
      region spanning approximately from nucleotide 1,300 to 2,750 was identical to a
      group of small Escherichia coli plasmids and encoded a putative replication
      protein identical to plasmid pKL1 Rep protein. The part with lower GC pairs
      seemed to be more specific as it showed no similarity to the GenBank database.
      Computational analysis revealed four open reading frames, two of which showed
      considerable homology to replication proteins. PCR primers targeting parts of the
      two different regions of plasmid pKST23 were used to assess the occurrence of
      related plasmids within ruminal E. coli population.

PMID- 22661061
TI  - Deciphering the metabolic capabilities of a lipase producing Pseudomonas
      aeruginosa SL-72 strain.
AB  - Pseudomonads have been reported for their metabolic, nutritional and ecological
      versatility, which motivated us to prospect the metabolic profile of a lipolytic
      strain Pseudomonas aeruginosa SL-72. The strain SL-72 was found to produce high
      levels of lipase and pectinase (1,555.62 IU/mL and 1,490.33 IU/mL, respectively),
      esterase and amylase, besides low levels of xylanase, proteinase and cellulase.
      The strain also tested positive for different plant growth-promoting traits
      production of ammonia, hydrogen cyanide, siderophores, phosphate solubilization,
      nitrate reduction and antifungal activity. The high levels of activity of aryl
      sulphatase, alkaline phosphatase and fluorescein diacetate hydrolase makes it a
      useful strain for enhanced nutrient cycling in soil. The strain SL-72 produced
      rhamnolipids, a biosurfactant and its production was enhanced when starch was
      used as carbon source (0.256 g/L) and utilized polycyclic hydrocarbon compounds
      viz. anthracene, phenanthrene, pyrene, fluorene and its mixture. The multifaceted
      nature of the culture illustrates its promise in bioremediation, industry,
      besides its use as an inoculant.

PMID- 22661062
TI  - Isolation of a thermophilic bacterium capable of low-molecular-weight
      polyethylene degradation.
AB  - A thermophilic bacterium capable of low-molecular-weight polyethylene (LMWPE)
      degradation was isolated from a compost sample, and was identified as
      Chelatococcus sp. E1, through sequencing of the 16S rRNA gene. LMWPE was prepared
      by thermal degradation of commercial PE in a strict nitrogen atmosphere. LMWPE
      with a weight-average-molecular-weight (Mw) in the range of 1,700-23,700 was
      noticeably mineralized into CO(2) by the bacterium. The biodegradability of LMWPE
      decreased as the Mw increased. The low molecular weight fraction of LMWPE
      decreased significantly as a result of the degradation process, and thereby both
      the number-average-molecular-weight and Mw increased after biodegradation. The
      polydispersity of LMWPE was either narrowed or widened, depending on the initial
      Mw of LMWPE, due to the preferential elimination of the low molecular weight
      fraction, in comparison to the high molecular weight portion. LMWPE free from an
      extremely low molecular weight fraction was also mineralized by the strain at a
      remarkable rate, and FTIR peaks assignable to C-O stretching appeared as a result
      of microbial action. The FTIR peaks corresponding to alkenes also became more
      intense, indicating that dehydrogenations occurred concomitantly with microbial
      induced oxidation.

PMID- 22661063
TI  - [Resources and their meaning for caregivers--a gap in research? Health
      sociological and empirical approach to a hitherto neglected field of research].
AB  - Family caregiving changes everyday life. Caregivers deal with the new situation
      in different ways and they feel more or less stressful. Actually there is little
      knowledge about possible causes of this situation. But there is an assumption
      that using varied resources and coping strategies lead to differences in health
      outcomes and well-being. As caregiving is a phase of life with special stressors,
      the caregiver needs specific resources to cope with these requirements. According
      to Antonovsky (1997) and Hobfoll (1989), this research asks which resources
      caregivers poses and use to deal with the unusual situation. On the basis of a
      salutogenetic and resource-orientated theoretical approach and additional
      qualitative analysis of interviews important resources for caregivers will be
      identified. The results lead on the one hand to the construction of an assessment
      instrument and on the other hand facilitate nurses to get to know more about the
      individual approach of resources and their specific meaning for caregivers.

PMID- 22661064
TI  - [The WHO pilot study on Family Health Nursing in Germany: perspectives of
      families in need of care--a qualitative study].
AB  - In the present study families were asked about their experiences with the first
      Family Health Nurses (FHN) educated in Germany according to WHO's concept. This
      education enables nurses and midwives to provide families and individuals a low
      threshold access to health care services. The study's aim was to gather
      information on how families perceive FHN's help and whether the curriculum meets
      their needs. Using a qualitative approach, eight families, for different reasons
      all caring for a next of kin at home, were interviewed. Data analysis followed
      Philip Burnard's method. Families describe FHN's assistance as "care and health
      related activities"or "managing everyday life". Furthermore they mention "Case
      Management" as part of FHN's activities. FHN's support contributes to stabilise
      family's situation. In addition, this analysis shows that Family Health Nurses
      correspond to the curriculum's contents in their daily work. Altogether, families
      with different care related, health related, and social related needs can benefit
      from FHN's support. This type of professional help relieves their personal
      situations. Families are empowered to handle their daily living and to develop
      new strategies to cope with challenges in their respective life situations.

PMID- 22661065
TI  - [Hepatitis C! Experience in diagnosis and medical treatment. A literature
      review].
AB  - Chronic hepatitis C can have physical, psychological or emotional effects on a
      person. The chronic infection can result in an advanced liver disease and/or
      influence daily life and self-perception. Today, the possibility to eliminate the
      virus exists but the therapy is difficult, a decrease in quality of life is
      known. Anyway, the sustained viral response isn't achievable for everyone. Care
      in Switzerland usually takes place in the outpatient clinics. Nurse participation
      to improve self-management is in discussion. For this specific work knowledge of
      patient's perception is crucial. A literature review was done to answer two
      questions: "What is the experience of the illness 'chronic hepatitis C'?" and
      additionally "What has to be managed when undergoing treatment?". A literature
      search was conducted in the databases of Pubmed and CINAHL. Seven qualitative
      studies were included. Diagnosis, contagion, illness, stigmatisation and fatigue
      are central themes and can influence each other. Discussion about treatment and
      the decision for it seems to be ambiguous. Patients feel reduced to their disease
      and demand for individual interventions especially for their experience with
      their illness. A targeted assessment seems important to appreciate their needs in
      each situation.

PMID- 22661066
TI  - [Comparative quality measurements part 1: run charts].
AB  - Quality assessment may be based on data of quality indicators. There are two main
      approaches for comparative quality measurements: comparison of data of the same
      service at different points over time or comparison of data of different services
      at the same time. Risk adjustment and standardisation must be performed and
      random variation must be adequately taken into account. In Statistical Process
      Control (SPC) theory common cause and special cause variation are distinguished.
      Processes in statistical control are stable and predictable. If processes exhibit
      special cause variation the management should investigate the reasons for this
      and manage the causes. Run charts as simple tools to display and analyse data of
      processes and outcomes over time are discussed in this article. They can be used
      for self-comparison. The following two parts of this three-part series explain
      control charts and funnel plots.

PMID- 22661067
TI  - [Can holistic rehabilitation process nursing in acute hospitals be implemented?
      1991].

PMID- 22661068
TI  - [Comment on the article by Krohwinkel: holistic rehabilitative care process
      relevant for today's nursing].

PMID- 22661070
TI  - Cronobacter condimenti sp. nov., isolated from spiced meat, and Cronobacter
      universalis sp. nov., a species designation for Cronobacter sp. genomospecies 1,
      recovered from a leg infection, water and food ingredients.
AB  - A re-evaluation of the taxonomic position of five strains, one assigned to
      Cronobacter sakazakii (strain 1330(T), isolated from spiced meat purchased in
      Slovakia), two previously assigned to Cronobacter genomospecies 1 (strains NCTC
      9529(T) and 731, isolated from water and a leg infection, respectively) and two
      previously assigned to Cronobacter turicensis (strains 96 and 1435, isolated from
      onion powder and rye flour, respectively) was carried out. The analysis included
      phenotypic characterization, 16S rRNA gene sequencing and multilocus sequence
      analysis (MLSA) of seven housekeeping genes (atpD, fusA, glnS, gltB, gyrB, infB,
      ppsA; 3036 bp). 16S rRNA gene sequence analysis and MLSA showed that strain
      1330(T) formed an independent phylogenetic lineage in the MLSA, with Cronobacter
      dublinensis LMG 23823(T) as the closest neighbour. DNA-DNA reassociation and
      phenotypic analysis revealed that strain 1330(T) represented a novel species, for
      which the name Cronobacter condimenti sp. nov. is proposed (type strain 1330(T) =
      CECT 7863(T) = LMG 26250(T)). Strains NCTC 9529(T), 731, 96 and 1435 clustered
      together within an independent phylogenetic lineage, with C. turicensis LMG
      23827(T) as the closest neighbour in the MLSA. DNA-DNA reassociation and
      phenotypic analysis confirmed that these strains represent a novel species, for
      which the name Cronobacter universalis sp. nov. is proposed (type strain NCTC
      9529(T) = CECT 7864(T) = LMG 26249(T)).

PMID- 22661071
TI  - Halobellus limi sp. nov. and Halobellus salinus sp. nov., isolated from two
      marine solar salterns.
AB  - Two halophilic archaea, strains TBN53(T) and CSW2.24.4(T), were characterized to
      elucidate their taxonomic status. Strain TBN53(T) was isolated from the Taibei
      marine solar saltern near Lianyungang city, Jiangsu province, China, whereas
      strain CSW2.24.4(T) was isolated from a saltern crystallizer in Victoria,
      Australia. Cells of the two strains were pleomorphic, stained Gram-negative and
      produced red-pigmented colonies. Strain TBN53(T) was able to grow at 25-55 
      degrees C (optimum 45  degrees C), with 1.4-5.1 M NaCl (optimum 2.6-3.9 M NaCl),
      with 0-1.0 M MgCl(2) (optimum 0-0.1 M MgCl(2)) and at pH 5.5-9.5 (optimum pH
      7.0), whereas strain CSW2.24.4(T) was able to grow at 25-45  degrees C (optimum
      37  degrees C), with 2.6-5.1 M NaCl (optimum 3.4 M NaCl), with 0.01-0.7 M MgCl(2)
      (optimum 0.05 M MgCl(2)) and at pH 5.5-9.5 (optimum pH 7.0-7.5). Cells of the two
      isolates lysed in distilled water. The minimum NaCl concentrations that prevented
      cell lysis were 8 % (w/v) for strain TBN53(T) and 12 % (w/v) for strain
      CSW2.24.4(T). The major polar lipids of the two strains were
      phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and
      phosphatidylglycerol sulfate, with two glycolipids chromatographically identical
      to sulfated mannosyl glucosyl diether and mannosyl glucosyl diether,
      respectively. Trace amounts of other unidentified lipids were also detected. On
      the basis of 16S rRNA gene sequence analysis, strains TBN53(T) and CSW2.24.4(T)
      showed 94.1 % similarity to each other and were closely related to Halobellus
      clavatus TNN18(T) (95.0 and 94.7 % similarity, respectively). Levels of rpoB'
      gene sequence similarity between strains TBN53(T) and CSW2.24.4(T), and between
      these strains and Halobellus clavatus TNN18(T) were 88.5, 88.5 and 88.1 %,
      respectively. The DNA G+C contents of strains TBN53(T) and CSW2.24.4(T) were 69.2
      and 67.0 mol%, respectively. The level of DNA-DNA relatedness between strain
      TBN53(T) and strain CSW2.24.4(T) was 25 %, and these two strains showed low
      levels of DNA-DNA relatedness with Halobellus clavatus TNN18(T) (30 and 29 %
      relatedness, respectively). Based on these phenotypic, chemotaxonomic and
      phylogenetic properties, two novel species of the genus Halobellus are proposed
      to accommodate these two strains, Halobellus limi sp. nov. (type strain TBN53(T)
      = CGMCC 1.10331(T) = JCM 16811(T)) and Halobellus salinus sp. nov. (type strain
      CSW2.24.4(T) = DSM 18730(T) = CGMCC 1.10710(T) = JCM 14359(T)).

PMID- 22661072
TI  - RAP2.6L overexpression delays waterlogging induced premature senescence by
      increasing stomatal closure more than antioxidant enzyme activity.
AB  - Waterlogging usually results from overuse or poor management of irrigation water
      and is a serious constraint due to its damaging effects. RAP2.6L (At5g13330)
      overexpression enhances plant resistance to jasmonic acid, salicylic acid,
      abscisic acid (ABA) and ethylene in Arabidopsis thaliana. However, it is not
      known whether RAP2.6L overexpression in vivo improves plant tolerance to
      waterlogging stress. In this study, the RAP2.6L transcript was induced by
      waterlogging or an ABA treatment, which was reduced after pretreatment with an
      ABA biosynthesis inhibitor tungstate. Water loss and membrane leakage were
      reduced in RAP2.6L overexpression plants under waterlogging stress. Time course
      analyses of ABA content and production of hydrogen peroxide (H(2)O(2)) showed
      that increased ABA precedes the increase of H(2)O(2). It is also followed by a
      marked increase in the antioxidant enzyme activities. Increased ABA promoted
      stomatal closure and made leaves exhibit a delayed waterlogging induced premature
      senescence. Furthermore, RAP2.6L overexpression caused significant increases in
      the transcripts of antioxidant enzyme genes APX1 (ascorbate peroxidase 1) and
      FSD1 (Fe-superoxide dismutase 1), the ABA biosynthesis gene ABA1 (ABA deficient
      1) and signaling gene ABH1 (ABA-hypersensitive 1) and the waterlogging responsive
      gene ADH1 (alcohol dehydrogenase 1), while the transcript of ABI1 (ABA
      insensitive 1) was decreased. ABA inhibits seed germination and seedling growth
      and phenotype analysis showed that the integration of abi1-1 mutation into the
      RAP2.6L overexpression lines reduces ABA sensitivity. These suggest that RAP2.6L
      overexpression delays waterlogging induced premature senescence and might
      function through ABI1-mediated ABA signaling pathway.

PMID- 22661073
TI  - A prospective study of quality of life including fatigue and pulmonary function
      after stereotactic body radiotherapy for medically inoperable early-stage lung
      cancer.
AB  - PURPOSE: The study seeks to prospectively evaluate pulmonary function and quality
      of life (QOL) in medically inoperable early-stage lung cancer patients undergoing
      stereotactic body radiotherapy (SBRT). METHODS: QOL was assessed by Functional
      Assessment of Cancer Therapy-Lung (FACT-L) and the UCSD Medical Center Pulmonary
      Rehabilitation Program Shortness-of-Breath Questionnaire before and after SBRT at
      6 weeks, and every 3 months until 12 months. Clinical investigations included
      pulmonary functions tests and blood profile and chemistries. SBRT was delivered
      on a Novalis/BrainLab system. RESULTS: Twenty-one analyzable patients were
      enrolled between July 2008 to April 2009. There were 12 males (52.4 %), 14
      patients (66.7 %) had Zubrod performance 1, the median age was 77 years (range 61
      90), and 87 % was inoperable because of pulmonary impairment. Median tumor size
      was 3.0 cm (range 1-4.6). Median follow-up was 17.6 months. One-year local
      control was 100 %. There were no significant changes in the median total FACT-L
      scores: 109 at baseline compared to 112 at 1 year. Mean UCSD scores were not
      significant for the year. No significant changes in mean baseline compared to 1
      year FEV1 and 6-min walks as % predicted were seen but a significant DLCO change
      (p = 0.012) was attributed to the decreased range in the standard deviations.
      CONCLUSIONS: Following SBRT, QOL is not significantly degraded. Pulmonary
      function is likewise not significantly impaired overall. Along with favorable
      survival results, these findings confirm that SBRT is appropriate for this
      patient population.

PMID- 22661074
TI  - Efficient preparation of selenium/glutathione-enriched Candida utilis and its
      biological effects on rats.
AB  - The main purpose of this study was to prepare selenium/glutathione-enriched
      Candida utilis and investigate its effect on growth performance, antioxidant
      capacity, and immune response in rats. The preparation of the
      selenium/glutathione-enriched yeast was conducted using fed-batch culture for
      high cell density. The optimal culture conditions for increased intracellular
      organic selenium and glutathione contents were as follows: the concentrated
      medium was fed beginning at 12 h using a polynomial feeding strategy until a
      total glucose concentration of 150 g/l was reached, and sodium selenite was
      continuously added together with glucose to a total concentration of 60 mg/l. As
      a result, 81 % of sodium selenite was assimilated and transformed into organic
      selenium by C. utilis under optimal conditions, which in turn resulted in greater
      glutathione accumulation and lower malondialdehyde cellular content in the yeast.
      To investigate and compare the effects of the prepared selenized C. utilis and
      other dietary supplements, 40 female rats were divided into five groups of eight
      rats each, following a randomized block design. Experimental feeding was
      conducted for a period of 6 weeks. Selenium supplementation with inorganic
      selenium (sodium selenite) and organic selenium (selenized C. utilis) showed
      better results than the control and other groups supplemented with yeast with or
      without glutathione. The body mass of rats, selenium deposition, and oxidative
      enzymes activities in both serum and liver samples, and immunity responses were
      all significantly improved by selenium supplementation, and between the two
      sources, organic selenium was more effective than inorganic selenium.

PMID- 22661075
TI  - Bilateral Mooren's ulcer in a child secondary to helminthic infestation of the
      gastrointestinal tract.
AB  - To report an unusual association of bilateral Mooren's ulcer in a child with
      helminthic infestation of gastrointestinal tract. A 6-year-old female presented
      with redness, watering and photophobia in left eye for 2 months and in right eye
      for 2 weeks. BCVA was 20/200 in OD and 20/400 OS. Superior peripheral corneal
      ulcer of 8 * 2 mm was present in the right eye and 8 * 3 mm perforated limbal
      corneal ulcer with staphyloma was present in the left eye. Hemogram revealed
      microcytic hypochromic anemia, eosinophilia and elevated ESR. No organism was
      isolated on corneal scraping. Stool examination revealed presence of Ancylostoma
      duodenale. Therapy included fortified topical antibiotics, cycloplegics,
      lubricants and oral albendazole. Conjunctival recession and crescentic
      therapeutic penetrating keratoplasty was done in OD and OS respectively. At 18
      months follow up, there was no recurrence in any of the eyes. Bilateral Mooren's
      ulcer may be present with gastrointestinal hookworm infestation. Prompt and
      appropriate management may provide optimal therapeutic success.

PMID- 22661076
TI  - Interobserver agreement for the detection of atherosclerotic plaque in coronary
      CT angiography: comparison of two low-dose image acquisition protocols with
      standard retrospectively ECG-gated reconstruction.
AB  - BACKGROUND: We compared the interobserver variability concerning the detection of
      calcified and non-calcified plaque in two different low-dose and standard
      retrospectively gated protocols for coronary CTA. METHODS: 150 patients with low
      heart rates and less than 100 kg body weight were randomised and examined by
      contrast-enhanced dual-source CT coronary angiography (100 kV, 320 mAs). 50
      patients were examined with prospectively ECG-triggered axial acquisition, 50
      patients with prospectively ECG-triggered high pitch spiral acquisition, and 50
      patients using spiral acquisition with retrospective ECG gating. Two
      investigators independently analysed the datasets concerning the presence of
      calcified and non-calcified plaque on a per-segment level. RESULTS: Mean
      effective dose was 1.4 +/- 0.2 mSv for axial, 0.8 +/- 0.07 mSv for high-pitch
      spiral, and 5.3 +/- 2.6 mSV for standard spiral acquisition (P < 0.0001). In
      axial acquisition, interobserver agreement concerning the presence of
      atherosclerotic plaque was achieved in 650/749 coronary segments (86.8%). In high
      pitch spiral acquisition, agreement was achieved in 664/748 segments (88.8%,
      n.s.). In standard spiral acquisition, agreement was achieved in 672/738 segments
      (91.0%, P < 0.0001). Interobserver agreement was significantly higher for
      calcified than for non-calcified plaque in all data acquisition modes.
      CONCLUSION: Low-dose coronary CT angiography permits the detection of coronary
      atherosclerotic plaque with good interobserver agreement. KEY POINTS: * Low-dose
      CT protocols permit coronary plaque detection with good interobserver agreement.
      * Image noise is a major predictor of interobserver variability. * Interobserver
      agreement is significantly higher for calcified than for non-calcified plaque.

PMID- 22661077
TI  - Retinal nerve changes in patients with tremor dominant and akinetic rigid
      Parkinson's disease.
AB  - Parkinson disease is a multisystem neurodegenerative disease which involves not
      only basal ganglia and extrapyramidal system but also many other neurologic
      systems such as retinal ganglion cells. Optical coherence tomography (OCT) is a
      non-invasive method for assessment of retinal nerve fiber layer (RNFL) thickness
      and its changes in different diseases. To evaluate the RNFL thickness in patients
      with Parkinson disease (PD), we performed OCT in patients with PD and compared it
      with a control group. From October 2010 to July 2011, 27 PD patients (54 eyes)
      and 25 healthy persons (50 eyes) were entered to this analytical cross-sectional
      study according to the defined criteria. PD patients were categorized into two
      groups "akinetic rigid (AR) and tremor dominant (TD)". RNFL was divided into four
      quadrants and was assessed by OCT. Afterwards; the data were analyzed by
      bivariate and multivariate models. The RNFL thickness in PD was significantly
      lower than the control group. Also, the thicknesses of inferior and nasal
      quadrants of RNFL in TD group were significantly more than AR group. According to
      these findings, OCT can be used as a sensitive and objective marker for
      assessment of early neurodegenerative changes of PD and early initiation of
      neuroprotective treatments. Future studies with adequate sample sizes are
      recommended to investigate interactions between age, distribution of the disease
      and type of PD as well as the effects of individual factors.

PMID- 22661078
TI  - Sex differences in the epidemiology, seasonal variation, and trends in the
      management of patients with acute appendicitis.
AB  - BACKGROUND: Acute appendicitis is the most common indication for acute surgical
      abdominal intervention. In this study, we analyzed the gender correlation with
      demographic, epidemiologic, diurnal, and seasonal trends in relation to the
      incidence and management of patients with acute appendicitis in our medical
      center. METHODS: Data of patients, 18 years of age or older who underwent
      emergency appendectomies at the Rabin Medical Center during the last 13 years,
      were collected. The data collected included demographic parameters,
      hospitalization, procedures, and use of preoperative imaging. RESULTS: Data were
      available for 3,736 patients. Males had more appendicitis attacks than females (p
      < 0.0001), whereas females had more normal appendixes than males (p < 0.0001).
      The overall rate of normal appendixes was 19.6 %, with a decline in the past 10
      years from a yearly average of 23.5 % between 1998 and 2002 to 15 % between 2003
      and 2007 (p < 0.0001) with a reverse correlation with the preoperative use of
      abdominal CT. A distinct seasonal pattern was observed; more appendectomies for
      acute appendicitis occurred during the summer months (p < 0.0001). Ten percent of
      patients had a complicated course with a mortality rate of 0.33 %; most of them
      were elderly, male/female ratio 0.4. CONCLUSIONS: We found distinct gender,
      epidemiological, seasonal, and diurnal trends influencing the incidence of acute
      appendicitis. The incidence rate of false-positive surgery has been gradually
      declining, probably due to the increased use of preoperative abdominal CT and
      ultrasound. Acute appendicitis was more common in males and during the summer
      months.

PMID- 22661079
TI  - Changes in morphology, cell wall composition and soluble proteome in Rhodobacter
      sphaeroides cells exposed to chromate.
AB  - The response of the carotenoidless Rhodobacter sphaeroides mutant R26 to chromate
      stress under photosynthetic conditions is investigated by biochemical and
      spectroscopic measurements, proteomic analysis and cell imaging. Cell cultures
      were found able to reduce chromate within 3-4 days. Chromate induces marked
      changes in the cellular dimension and morphology, as revealed by atomic force
      microscopy, along with compositional changes in the cell wall revealed by
      infrared spectroscopy. These effects are accompanied by significant changes in
      the level of several proteins: 15 proteins were found up-regulated and 15 down
      regulated. The protein content found in chromate exposed cells is in good
      agreement with the biochemical, spectroscopic and microscopic results. Moreover
      at the present stage no specific chromate-reductase could be found in the soluble
      proteome, indicating that detoxification of the pollutant proceeds via aspecific
      reductants.

PMID- 22661080
TI  - Effect of phosphate-solubilizing fungi Aspergillus awamori S29 on mungbean (Vigna
      radiata cv. RMG 492) growth.
AB  - A phosphate solubilizing fungus, Aspergillus awamori S29 was isolated from
      rhizoshpere of mungbean. The phosphate solubilizing activity of A. awamori S29 in
      liquid was 1,110 mg/L for tricalcium phosphate (TCP). The organism was able to
      solubilize various inorganic forms of phosphate at a wide range of temperatures.
      Among various insoluble phosphate sources tested, di-calcium phosphate was
      solubilized the most, followed by TCP. A. awamori S29 had significant effect (p <
      0.05) on mungbean growth, total P and plant biomass under pot conditions,
      although no obvious difference in available P in soil and number of leaves was
      found compared to the control.

PMID- 22661081
TI  - Investigation of spinal posture signatures and ground reaction forces during
      landing in elite female gymnasts.
AB  - The link between static and dynamic landing lumbar postures, when gymnasts are
      exposed to large ground reaction forces, has not been established. This
      investigation aimed to (a) determine if a relationship exists between sagittal
      static and dynamic landing lumbar spine angles at peak ground reaction force
      (GRF) and (b) quantify how close to end-range postures the gymnasts were at
      landing peak GRF. Twenty-one female gymnasts' upper and lower lumbar spine angles
      were recorded: statically in sitting and standing, during landing of three
      gymnastic skills, and during active end-range lumbar flexion. Pearson's
      correlations were used to investigate relationships between the angles in
      different postures. Significant correlations (r = .77-.89, p <.01) were found
      between all the static/dynamic postures in the lower lumbar spine angle, while
      fewer and less significant upper lumbar spine correlations were reported. Thirty
      percent of gymnasts landed a backsault with their lower lumbar spine flexed
      beyond their active end-range while experiencing GRF 6.8-13.3 times their body
      weight. These results inform low back pain prevention and management strategies
      in this population and highlight areas for future research.

PMID- 22661083
TI  - Vasoactive intestinal peptide downregulates proinflammatory TLRs while
      upregulating anti-inflammatory TLRs in the infected cornea.
AB  - TLRs recognize microbial pathogens and trigger an immune response, but their
      regulation by neuropeptides, such as vasoactive intestinal peptide (VIP), during
      Pseudomonas aeruginosa corneal infection remains unexplored. Therefore, C57BL/6
      (B6) mice were injected i.p. with VIP, and mRNA, protein, and immunostaining
      assays were performed. After VIP treatment, PCR array and real-time RT-PCR
      demonstrated that proinflammatory TLRs (conserved helix-loop-helix ubiquitous
      kinase, IRAK1, TLR1, TLR4, TLR6, TLR8, TLR9, and TNFR-associated factor 6) were
      downregulated, whereas anti-inflammatory TLRs (single Ig IL-1-related receptor
      [SIGIRR] and ST2) were upregulated. ELISA showed that VIP modestly downregulated
      phosphorylated inhibitor of NF-kappaB kinase subunit alpha but upregulated ST2 ~2
      fold. SIGIRR was also upregulated, whereas TLR4 immunostaining was reduced in
      cornea; all confirmed the mRNA data. To determine whether VIP effects were cAMP
      dependent, mice were injected with small interfering RNA for type 7 adenylate
      cyclase (AC7), with or without VIP treatment. After silencing AC7, changes in
      mRNA levels of TLR1, TNFR-associated factor 6, and ST2 were seen and unchanged
      with addition of VIP, indicating that their regulation was cAMP dependent. In
      contrast, changes were seen in mRNA levels of conserved helix-loop-helix
      ubiquitous kinase, IRAK1, 2, TLR4, 9 and SIGIRR following AC7 silencing alone;
      these were modified by VIP addition, indicating their cAMP independence. In vitro
      studies assessed the effects of VIP on TLR regulation in macrophages and
      Langerhans cells. VIP downregulated mRNA expression of proinflammatory TLRs while
      upregulating anti-inflammatory TLRs in both cell types. Collectively, the data
      provide evidence that VIP downregulates proinflammatory TLRs and upregulates anti
      inflammatory TLRs and that this regulation is both cAMP dependent and independent
      and involves immune cell types found in the infected cornea.

PMID- 22661084
TI  - B7-H1, which represses EBV-immortalized B cell killing by autologous T and NK
      cells, is oppositely regulated by c-Myc and EBV latency III program at both mRNA
      and secretory lysosome levels.
AB  - EBV-immortalized B cells induce a complex immune response such that the virus
      persists as a clinically silent infection for the lifetime of the infected host.
      B7-H1, also called PD-L1, is a cosignaling molecule of the B7 family that can
      inhibit activated T cell effectors by interaction with its receptor PD-1. In this
      work, we have studied the dependence of B7-H1 on NF-kappaB and c-Myc, the two
      main transcription factors in EBV latency III proliferating B cells, on various
      lymphoblastoid and Burkitt lymphoma cell lines, some of them being inducible or
      not for the EBV latency III program and/or for c-Myc. We found that B7-H1
      repressed killing of EBV-immortalized B cells by their autologous T and NK cells.
      At the mRNA level, NF-kappaB was a weak inducer whereas c-Myc was a strong
      repressor of B7-H1 expression, an effect mediated by STAT1 inhibition. At the
      protein level, B7-H1 molecules were stored in both degradative and unconventional
      secretory lysosomes. Surface membrane B7-H1 molecules were constitutively
      internalized and proteolyzed in lysosomes. The EBV latency III program increased
      the amounts of B7-H1-containing secretory lysosomes and their export to the
      surface membrane. By repressing actin polymerization, c-Myc blocked secretory
      lysosome migration and B7-H1 surface membrane export. In addition to B7-H1,
      various immunoregulatory molecules participating in the immunological synapse are
      stored in secretory lysosomes. By playing on actin polymerization, c-Myc could
      thus globally regulate the immunogenicity of transformed B cells, acting on
      export of secretory lysosomes to plasma membrane.

PMID- 22661085
TI  - IL-33 priming regulates multiple steps of the neutrophil-mediated anti-Candida
      albicans response by modulating TLR and dectin-1 signals.
AB  - IL-33 is known to play an important role in Th2 immunity. In this study, we
      investigated the effect of IL-33 pretreatment on anti-fungal response using an
      acute Candida albicans peritoneal infection model. IL-33 pretreatment induced a
      rapid fungal clearance and markedly reduced the C. albicans infection-associated
      mortality. The priming effect of IL-33 occurred during multiple steps of the
      neutrophil-mediated anti-fungal response. First, the anti-fungal effect occurred
      due to the rapid and massive recruitment of neutrophils to the site of infection
      as a result of the release of CXCR2 chemokines by peritoneal macrophages and by
      reversal of the TLR-induced reduction of CXCR2 expression in neutrophils during
      IL-33 priming. Second, conditioning of neutrophils by IL-33 activated the TLR and
      dectin-1 signaling pathways, leading to the upregulation of complement receptor 3
      expression induced by C. albicans. Upregulated CR3 in turn increased the
      phagocytosis of opsonized C. albicans and resulted in the production of high
      levels of reactive oxygen species and the subsequent enhanced killing activity of
      neutrophils. Taken together, our results suggest that IL-33 can regulate the anti
      fungal activity of neutrophils by collaborative modulation of the signaling
      pathways of different classes of innate immune receptors.

PMID- 22661087
TI  - Zinc supplementation during pregnancy protects against lipopolysaccharide-induced
      fetal growth restriction and demise through its anti-inflammatory effect.
AB  - LPS is associated with adverse developmental outcomes, including preterm
      delivery, fetal death, teratogenicity, and intrauterine growth restriction
      (IUGR). Previous reports showed that zinc protected against LPS-induced
      teratogenicity. In the current study, we investigated the effects of zinc
      supplementation during pregnancy on LPS-induced preterm delivery, fetal death and
      IUGR. All pregnant mice except controls were i.p. injected with LPS (75 MUg/kg)
      daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered
      zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the
      pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17
      resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed
      the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced
      fetal weight and crown-rump length. Of interest, zinc supplementation during
      pregnancy protected mice from LPS-induced preterm delivery and fetal death. In
      addition, zinc supplementation significantly alleviated LPS-induced IUGR and
      skeletal development retardation. Further experiments showed that zinc
      supplementation significantly attenuated LPS-induced expression of placental
      inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also
      significantly attenuated LPS-induced activation of NF-kappaB and MAPK signaling
      in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It
      inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc
      supplementation during pregnancy protects against LPS-induced fetal growth
      restriction and demise through its anti-inflammatory effect.

PMID- 22661086
TI  - TLR signaling prevents hyperoxia-induced lung injury by protecting the alveolar
      epithelium from oxidant-mediated death.
AB  - Mechanical ventilation using high oxygen tensions is often necessary to treat
      patients with respiratory failure. Recently, TLRs were identified as regulators
      of noninfectious oxidative lung injury. IRAK-M is an inhibitor of MyD88-dependent
      TLR signaling. Exposure of mice deficient in IRAK-M (IRAK-M(-/-)) to 95% oxygen
      resulted in reduced mortality compared with wild-type mice and occurred in
      association with decreased alveolar permeability and cell death. Using a bone
      marrow chimera model, we determined that IRAK-M's effects were mediated by
      structural cells rather than bone marrow-derived cells. We confirmed the
      expression of IRAK-M in alveolar epithelial cells (AECs) and showed that
      hyperoxia can induce the expression of this protein. In addition, IRAK-M(-/-)
      AECs exposed to hyperoxia experienced a decrease in cell death. IRAK-M may
      potentiate hyperoxic injury by suppression of key antioxidant pathways, because
      lungs and AECs isolated from IRAK-M(-/-) mice have increased expression/activity
      of heme oxygenase-1, a phase II antioxidant, and NF (erythroid-derived)-related
      factor-2, a transcription factor that initiates antioxidant generation. Treatment
      of IRAK-M(-/-) mice in vivo and IRAK-M(-/-) AECs in vitro with the heme oxygenase
      1 inhibitor, tin protoporphyrin, substantially decreased survival and
      significantly reduced the number of live cells after hyperoxia exposure.
      Collectively, our data suggest that IRAK-M inhibits the induction of antioxidants
      essential for protecting the lungs against cell death, resulting in enhanced
      susceptibility to hyperoxic lung injury.

PMID- 22661088
TI  - TLR5, a novel and unidentified inflammatory mediator in rheumatoid arthritis that
      correlates with disease activity score and joint TNF-alpha levels.
AB  - The innate immune system plays an important role in rheumatoid arthritis (RA)
      pathogenesis. Previous studies support the role of TLR2 and 4 in RA and
      experimental arthritis models; however, the regulation and pathogenic effect of
      TLR5 is undefined in RA. In this study, we show that TLR5 is elevated in RA and
      osteoarthritis ST lining and sublining macrophages and endothelial cells compared
      with normal individuals. Furthermore, expression of TLR5 is elevated in RA
      synovial fluid macrophages and RA peripheral blood monocytes compared with RA and
      normal peripheral blood in vitro-differentiated macrophages. We also found that
      TLR5 on RA monocytes is an important modulator of TNF-alpha in RA synovial fluid
      and that TLR5 expression on these cells strongly correlates with RA disease
      activity and TNF-alpha levels. Interestingly, TNF-alpha has a feedback regulation
      with TLR5 expression in RA monocytes, whereas expression of this receptor is
      regulated by IL-17 and IL-8 in RA macrophages and fibroblasts. We show that RA
      monocytes and macrophages are more responsive to TLR5 ligation compared with
      fibroblasts despite the proinflammatory response being mediated through the same
      signaling pathways in macrophages and fibroblasts. In conclusion, we document the
      potential role of TLR5 ligation in modulating transcription of TNF-alpha from RA
      synovial fluid and the strong correlation of TLR5 and TNF-alpha with each other
      and with disease activity score in RA monocytes. Our results suggest that
      expression of TLR5 may be a predictor for RA disease progression and that
      targeting TLR5 may suppress RA.

PMID- 22661090
TI  - Comprehensive analysis of CD4+ T cells in the decision between tolerance and
      immunity in vivo reveals a pivotal role for ICOS.
AB  - We have established a comprehensive in vivo mouse model for the CD4(+) T cell
      response to an "innocuous" versus "dangerous" exogenous Ag and developed an in
      vivo test for tolerance. In this model, specific gene-expression signatures,
      distinctive upregulation of early T cell-communication molecules, and
      differential expansion of effector T cells (Teff) and regulatory T cells (Treg)
      were identified as central correlates of T cell tolerance and T cell immunity.
      Different from essentially all other T cell-activation molecules, ICOS was found
      to be induced in the immunity response and not by T cells activated under
      tolerogenic conditions. If expressed, ICOS did not act as a general T cell
      costimulator but selectively caused a massive expansion of effector CD4(+) T
      cells, leaving the regulatory CD4(+) T cell compartment largely undisturbed.
      Thus, ICOS strongly contributed to the dramatic change in the balance between Ag
      specific Teff and Treg from ~1:1 at steady state to 21:1 at the height of the
      immune response. This newly defined role for the balance of Teff to Treg,
      together with its known key function in T cell help for B cells, establishes ICOS
      as a central mediator of immunity. Given its exceptionally selective induction on
      CD4(+) T cells under inflammatory, but not tolerogenic, conditions, ICOS emerges
      as a pivotal effector molecule in the early decision between tolerance and
      immunity to exogenous Ag.

PMID- 22661089
TI  - Myeloid dendritic cells from B6.NZM Sle1/Sle2/Sle3 lupus-prone mice express an
      IFN signature that precedes disease onset.
AB  - Patients with systemic lupus erythematosus show an overexpression of type I IFN
      responsive genes that is referred to as "IFN signature." We found that
      B6.NZMSle1/Sle2/Sle3 (Sle1,2,3) lupus-prone mice also express an IFN signature
      compared with non-autoimmune C57BL/6 mice. In vitro, myeloid dendritic cells
      (mDCs) (GM-CSF bone marrow-derived dendritic cells; BMDCs) from Sle1,2,3 mice
      constitutively overexpressed IFN-responsive genes such as IFN-beta, Oas-3, Mx-1,
      ISG-15, and CXCL10 and members of the IFN signaling pathway STAT1, STAT2, and
      IRF7. The IFN signature was similar in Sle1,2,3 BMDCs from young, pre-autoimmune
      mice and from mice with high titers of autoantibodies, suggesting that the IFN
      signature in mDCs precedes disease onset and is independent from the
      autoantibodies. Sle1,2,3 BMDCs hyperresponded to stimulation with IFN-alpha and
      the TLR7 and TLR9 agonists R848 and CpGs. We propose that this hyperresponse is
      induced by the IFN signature and only partially contributes to the signature, as
      oligonucleotides inhibitory for TLR7 and TLR9 only partially suppressed the
      constitutive IFN signature, and pre-exposure to IFN-alpha induced the same
      hyperresponse in wild-type BMDCs as in Sle1,2,3 BMDCs. In vivo, mDCs and to a
      lesser extent T and B cells from young prediseased Sle1,2,3 mice also expressed
      the IFN signature, although they lacked the strength that BMDCs showed in vitro.
      Sle1,2,3 plasmacytoid DCs expressed the IFN signature in vitro but not in vivo,
      suggesting that mDCs may be more relevant before disease onset. We propose that
      Sle1,2,3 mice are useful tools to study the role of the IFN signature in lupus
      pathogenesis.

PMID- 22661091
TI  - Neutrophil cerebrovascular transmigration triggers rapid neurotoxicity through
      release of proteases associated with decondensed DNA.
AB  - Cerebrovascular inflammation contributes to diverse CNS disorders through
      mechanisms that are incompletely understood. The recruitment of neutrophils to
      the brain can contribute to neurotoxicity, particularly during acute brain
      injuries, such as cerebral ischemia, trauma, and seizures. However, the
      regulatory and effector mechanisms that underlie neutrophil-mediated
      neurotoxicity are poorly understood. In this study, we show that mouse
      neutrophils are not inherently toxic to neurons but that transendothelial
      migration across IL-1-stimulated brain endothelium triggers neutrophils to
      acquire a neurotoxic phenotype that causes the rapid death of cultured neurons.
      Neurotoxicity was induced by the addition of transmigrated neutrophils or
      conditioned medium, taken from transmigrated neutrophils, to neurons and was
      partially mediated by excitotoxic mechanisms and soluble proteins. Transmigrated
      neutrophils also released decondensed DNA associated with proteases, which are
      known as neutrophil extracellular traps. The blockade of histone-DNA complexes
      attenuated transmigrated neutrophil-induced neuronal death, whereas the
      inhibition of key neutrophil proteases in the presence of transmigrated
      neutrophils rescued neuronal viability. We also show that neutrophil recruitment
      in the brain is IL-1 dependent, and release of proteases and decondensed DNA from
      recruited neutrophils in the brain occurs in several in vivo experimental models
      of neuroinflammation. These data reveal new regulatory and effector mechanisms of
      neutrophil-mediated neurotoxicity (i.e., the release of proteases and decondensed
      DNA triggered by phenotypic transformation during cerebrovascular
      transmigration). Such mechanisms have important implications for
      neuroinflammatory disorders, notably in the development of antileukocyte
      therapies.

PMID- 22661092
TI  - Retinoid X receptor agonists impair arterial mononuclear cell recruitment through
      peroxisome proliferator-activated receptor-gamma activation.
AB  - Mononuclear cell migration into the vascular subendothelium constitutes an early
      event of the atherogenic process. Because the effect of retinoid X receptor
      (RXR)alpha on arterial mononuclear leukocyte recruitment is poorly understood,
      this study investigated whether RXR agonists can affect this response and the
      underlying mechanisms involved. Decreased RXRalpha expression was detected after
      4 h stimulation of human umbilical arterial endothelial cells with TNF-alpha.
      Interestingly, under physiological flow conditions, TNF-alpha-induced endothelial
      adhesion of human mononuclear cells was concentration-dependently inhibited by
      preincubation of the human umbilical arterial endothelial cells with RXR agonists
      such as bexarotene or 9-cis-retinoid acid. RXR agonists also prevented TNF-alpha
      induced VCAM-1 and ICAM-1 expression, as well as endothelial growth-related
      oncogene-alpha and MCP-1 release. Suppression of RXRalpha expression with a small
      interfering RNA abrogated these responses. Furthermore, inhibition of MAPKs and
      NF-kappaB pathways were involved in these events. RXR agonist-induced
      antileukocyte adhesive effects seemed to be mediated via RXRalpha/peroxisome
      proliferator-activated receptor (PPAR)gamma interaction, since endothelial
      PPARgamma silencing abolished their inhibitory responses. Furthermore, RXR
      agonists increased RXR/PPARgamma interaction, and combinations of suboptimal
      concentrations of both nuclear receptor ligands inhibited TNF-alpha-induced
      mononuclear leukocyte arrest by 60-65%. In vivo, bexarotene dose-dependently
      inhibited TNF-alpha-induced leukocyte adhesion to the murine cremasteric
      arterioles and decreased VCAM-1 and ICAM-1 expression. Therefore, these results
      reveal that RXR agonists can inhibit the initial inflammatory response that
      precedes the atherogenic process by targeting different steps of the mononuclear
      recruitment cascade. Thus, RXR agonists may constitute a new therapeutic tool in
      the control of the inflammatory process associated with cardiovascular disease.

PMID- 22661093
TI  - B7-H3 participates in the development of experimental pneumococcal meningitis by
      augmentation of the inflammatory response via a TLR2-dependent mechanism.
AB  - In addition to a well-documented role in regulating T cell-mediated immune
      responses, B7-H3, a newly discovered member of the B7 superfamily, has been
      recently identified as a costimulator in the innate immunity-mediated
      inflammatory response. In this study, we further report that B7-H3 participates
      in the development of pneumococcal meningitis in a murine model. Exogenous
      administration of B7-H3 strongly amplified the inflammatory response, exacerbated
      blood-brain barrier disruption, and aggravated the clinical disease status in
      Streptococcus pneumoniae-infected C3H/HeN wild-type mice. Consistent with the in
      vivo findings, B7-H3 substantially augmented proinflammatory cytokine and
      chemokine production, upregulated NF-kappaB p65 and MAPK p38 phosphorylation, and
      enhanced the nuclear transactivation of NF-kappaB p65 at both TNF-alpha and IL-6
      promoters in S. pneumoniae-stimulated primary murine microglia cells. These B7-H3
      associated in vitro and in vivo effects appeared to be dependent on TLR2
      signaling, as B7-H3 almost completely lost its amplifying actions in both TLR2
      deficient microglial cells and TLR2-deficient mice. Furthermore, administration
      of the anti-B7-H3 mAb (MIH35) attenuated the inflammatory response and
      ameliorated blood-brain barrier disruption in S. pneumoniae-infected wild-type
      mice. Collectively, our results indicate that B7-H3 plays a contributory role in
      the development of S. pneumoniae infection-induced bacterial meningitis.

PMID- 22661094
TI  - Cutting edge: microRNA regulation of macrophage fusion into multinucleated giant
      cells.
AB  - Cellular fusion of macrophages into multinucleated giant cells is a
      distinguishing feature of the granulomatous response to inflammation, infection,
      and foreign bodies (Kawai and Akira. 2011. Immunity 34: 637-650). We observed a
      marked increase in fusion of macrophages genetically deficient in Dicer, an
      enzyme required for canonical microRNA (miRNA) biogenesis. Gene expression
      profiling of miRNA-deficient macrophages revealed an upregulation of the IL-4
      responsive fusion protein Tm7sf4, and analyses identified miR-7a-1 as a negative
      regulator of macrophage fusion, functioning by directly targeting Tm7sf4 mRNA.
      miR-7a-1 is itself an IL-4-responsive gene in macrophages, suggesting feedback
      control of cellular fusion. Collectively, these data indicate that miR-7a-1
      functions to regulate IL-4-directed multinucleated giant cell formation.

PMID- 22661095
TI  - Hepatitis B virus-induced calreticulin protein is involved in IFN resistance.
AB  - IFN-alpha is a widely used treatment for hepatitis B virus (HBV) infection, and
      IFN resistance caused by viral and/or host factors is currently a challenging
      clinical problem. A better understanding of the molecular mechanisms underlying
      IFN immunotherapy in the treatment of viral infection would be very beneficial
      clinically and is of immense clinical importance. Calreticulin (CRT) is an
      endoplasmic reticulum luminal calcium-binding chaperone that is involved in the
      regulation of calcium homoeostasis, the folding of newly synthesized proteins,
      and many other cellular functions. However, little is known about the role of CRT
      in HBV infection. In this study, we observed high levels of CRT expression in the
      sera and PBMCs of patients with HBV relative to those of healthy individuals. HBV
      upregulated the expression of CRT at the transcriptional level. Further
      investigation showed that HBV-induced CRT enhanced HBV replication by
      antagonizing the IFN pathway. CRT suppressed the production of endogenous IFN
      alpha by reducing the nuclear translocation of IFN regulatory factor-7 but not
      IFN regulatory factor-3. Furthermore, CRT also suppressed the antiviral activity
      of IFN-alpha by inhibiting the phosphorylation of STAT1 and decreasing the
      expression of two IFN-alpha downstream effectors, protein kinase R and 2',5'
      oligoadenylate synthetase. Our results offer new insights into the pathogenesis
      of HBV infection and may provide potential targets for anti-HBV therapy.

PMID- 22661096
TI  - Walking a mile in their shoes: anxiety and depression among partners and
      caregivers of cancer survivors at 6 and 12 months post-diagnosis.
AB  - PURPOSE: This study aims to examine the prevalence of psychosocial variables
      associated with anxiety and depression among partners and caregivers of cancer
      survivors, compare prevalence with community norms and report differences across
      cancer diagnosis. METHODS: A prospective survey of partners and caregivers was
      undertaken to assess anxiety and depression and potential psychosocial variables
      associated with these outcomes at 6 and 12 months post-survivor diagnosis (N =
      436). RESULTS: Although the proportion of anxious participants decreased over
      time (p = 0.01), the percentage of those depressed remained stable (p = 0.68).
      Most participants who were depressed were also anxious. To a certain extent, the
      prevalence of anxiety and depression exceeded community norms and varied across
      cancer types. Partners and caregivers particularly vulnerable included those of
      lung, haematological or head and neck survivors. High use of avoidant coping and
      interference in regular activities were associated with both anxiety and
      depression across time points. Of the different types of support measured, only
      lower emotional/informational support was associated with anxiety and depression
      at 6 months, whereas lower positive social interaction was associated with
      depression at 12 months. Additional variables associated with anxiety and
      depression at 12 months included higher unmet needs and involvement in personal
      and medical tasks, respectively. CONCLUSIONS: Even at 12 months post-survivor
      diagnosis, almost a third of participants reported anxiety, a result partially
      predicted by high use of avoidant coping and interference in regular activities.
      Understanding variables associated with partners' and caregivers' anxiety and
      depression can lead to optimal referral to supportive care services and inform
      the tailoring of interventions to address those variables contributing to anxiety
      and depression at particular time points.

PMID- 22661097
TI  - Efficacy of landiolol hydrochloride for atrial fibrillation after open heart
      surgery.
AB  - It is important to establish effective treatment for postoperative atrial
      fibrillation (AF), the most common complication after cardiac surgery. We
      evaluated the efficacy and safety of landiolol hydrochloride for rhythm
      conversion in patients with postoperative AF. Among 134 patients who developed
      new-onset AF after open heart surgery between 2007 and 2009, 69 patients who
      received landiolol hydrochloride for treatment of postoperative AF were enrolled.
      The AF conversion rate, the percentage of patients with 20 % reduction of the
      ventricular rate, and the factors related to successful treatment were evaluated.
      Then, the landiolol group was compared with 65 patients who had postoperative AF
      and did not receive landiolol hydrochloride. Landiolol hydrochloride was the
      first-line treatment in 46 patients and the only therapy in 26 patients.
      Reversion to sinus rhythm was achieved in 51 patients, while the conversion rate
      in patients without landiolol hydrochloride was only 56.8 % (p < 0.05). A 20 %
      reduction of the ventricular rate was achieved more frequently in the landiolol
      group. Although landiolol hydrochloride was highly effective in patients who had
      undergone off-pump coronary artery bypass grafting, patients with cardiopulmonary
      bypass did not respond as well. The heart rate was reduced from 130 +/- 26 to 81
      +/- 12 (p < 0.05) after landiolol administration, while blood pressure did not
      decrease significantly. Landiolol hydrochloride was effective for conversion of
      postoperative AF. This ultra-short-acting beta-blocker is a safe first-line
      treatment for postoperative AF after open heart surgery, and is most effective in
      patients who have undergone off-pump coronary artery bypass grafting.

PMID- 22661098
TI  - Home haemodialysis in Ireland.
AB  - BACKGROUND: A home haemodialysis programme (HHD) was established in Ireland in
      2009 following studies suggesting better outcomes and a survival advantage when
      compared to conventional in-centre dialysis. AIM: The aim of this study was to
      assess the outcomes in patients commenced on the HHD programme. METHODS: Baseline
      characteristics, standard dialysis parameters, blood pressure control,
      antihypertensive usage, vascular access problems, hospitalisation rates and
      technical issues related to dialysis were analysed. RESULTS: Seventeen patients
      were followed over a 2-year period. Time spent travelling for dialysis-related
      treatments was reduced with time on dialysis per week increased. There was a
      trend towards lower blood pressure with nine patients, either discontinuing or
      having a reduction in antihypertensive medications. There were eight episodes of
      hospitalisation with the majority of complications related to vascular access.
      CONCLUSION: Home haemodialysis is a community-based therapy, offering an
      alternative to conventional in-centre haemodialysis in a select patient
      population.

PMID- 22661099
TI  - Biological drugs: classic adverse effects and new clinical evidences.
AB  - The last 20 years was characterized by great improvements in the efficacy and
      tolerability of anticancer therapies. Most of these changes are related to the
      introduction of targeted drugs, which presents a better activity on the biology
      of cancer and less toxicity. Nevertheless, the initial enthusiasm was cooled by
      the emerging evidences of cardiac side effects. The aim of this review is to
      describe the actual knowledge about the possible cardiotoxicity of targeted
      drugs. The most important need is the detection of early cardiotoxicity and the
      evidence of subtle myocardial dysfunction that allows to begin a protective
      therapy. In our review we analyzed the non invasive imaging techniques to early
      predict myocardial dysfunction. Echocardiography seems to be the ideal method for
      her availability, safety and clinical usefulness, in particular the new
      echocardiographic techniques like speckle tracking.

PMID- 22661100
TI  - Health-related quality of life after Ivor Lewis esophagectomy.
AB  - PURPOSE: Transthoracic Ivor Lewis esophagectomy is a surgical standard therapy
      for esophageal carcinoma. The aim of this study was to assess health-related
      quality of life (HRQL) in mid- and long-term survivors. METHODS: Patients with
      cancer-free survival of at least 12 months after esophageal resection for cancer
      were identified from a prospectively maintained database. EORTC questionnaires
      were sent out to assess health-related general (QLQ-C30) and esophageal cancer
      specific (QLQ-OES18) quality of life (QOL). A numeric score was calculated in
      each conceptual area and compared with reference data. RESULTS: One hundred forty
      seven patients completed the self-rated questionnaires. They were 121 men and 26
      women with a mean age of 63.4 (21-83) years; median FU was 39 (12-139) months.
      Global health status, functional scales, and symptom scores were significantly
      reduced compared with healthy reference populations. Also, there was no
      significant impact of tumor histology, neoadjuvant treatment, minimally invasive
      approach, or duration of follow-up on HRQL. However, more than half of the
      patients reported a HRQL similar to that of the healthy reference population.
      CONCLUSIONS: Despite the major psychosocial and physiological impacts of the
      disease, more than 50 % of mid- and long-term survivors of the Ivor Lewis
      procedure for esophageal cancer have a HRQL similar to that of the healthy
      reference population.

PMID- 22661101
TI  - Components of metabolic syndrome and risk of breast cancer by prognostic features
      in the study of osteoporotic fractures cohort.
AB  - PURPOSE: Metabolic syndrome (MetS) and most of its components have been
      previously associated with increased breast cancer risk. We hypothesized that
      increasing number of MetS components would be positively associated with breast
      cancer risk. METHODS: Data were obtained from the Study of Osteoporotic
      Fractures, a prospective cohort of women aged >=65 enrolled between 1986 and 1988
      and still being followed prospectively (n = 8,956). MetS components evaluated at
      baseline were elevated waist circumference, hypertension, and diabetes. Data were
      not available on hyperlipidemia. Incident breast cancers were confirmed by
      pathology report. We compared women with 0, 1, and 2 or 3 MetS components. We
      used Cox proportional hazards regression to calculate associations for breast
      cancer overall and classified by prognostic features. RESULTS: At baseline, 28.8
      % of participants had 2 or 3 MetS components. Over an average follow-up of 14.4
      years, 551 breast cancer cases were identified. Compared to those with no
      components, women with 2 or 3 components had increased breast cancer risk (hazard
      ratio (HR), 1.30; 95 % confidence interval (CI), 1.01-1.68) and increased risk of
      ER+ (HR, 1.48; 95 % CI, 1.09-2.03) and PR+ (HR, 1.56; 95 % CI, 1.10-2.20) cancer,
      adjusting for age, hormone use, and family history of breast cancer. These
      results became attenuated and not statistically significant when additionally
      adjusted for body mass index. CONCLUSIONS: MetS is associated with increased
      postmenopausal breast cancer risk, especially for ER+ and PR+ cancers, though
      this effect may not be independent of the effect of body mass index. Managing the
      components of MetS could be efficacious for breast cancer risk reduction.

PMID- 22661102
TI  - An unusual case of neuro-Behcet's disease presenting with co-occurence of
      cerebral venous sinus thrombosis with basilar artery occlusion.
AB  - Non-parenchymal neuro-Behcet disease generally affects cerebral venous sinuses,
      whereas intracranial intracerebral arterial involvement has been rarely reported.
      But co-involvement of both intracranial intracerebral artery and venous vascular
      systems in a patient at the same time has not been mentioned before. To the best
      of our knowledge, this case involving a 25-year-old male with a 7-year history of
      Behcet disease is the first reported of this type of involvement. He developed
      occlusion of the basilar artery together with thrombosis of the left sigmoid
      sinus, distal internal jugular vein, and straight sinus. He was successfully
      treated with a combination of high-dose steroid and cyclophosphamide. Cranial
      magnetic resonance angiography demonstrated the resolution of these
      abnormalities.

PMID- 22661103
TI  - Antioxidant activity of topiramate: an antiepileptic agent.
AB  - A number of experimental and clinical reports suggest the involvement of
      oxidative stress in pathophysiology of epilepsy. Topiramate, a new antiepileptic
      drug, induces antioxidant effect in epileptic animals. However, to date, no
      further studies appear to be carried out in order to demonstrate the ability of
      topiramate to act as antioxidant. Therefore, the objective of this work was to
      evaluate the in vitro superoxide (O2(.-)), hydroxyl radical (OH.), hypochlorous
      acid (HOCl), hydrogen peroxide (H2O2), singlet oxygen ((1)O2) and peroxynitrite
      (ONOO(-)) scavenging capacity of topiramate in comparison with reference
      compounds. In addition, we investigated the possible antitumour activity of this
      compound in some cancer cell lines. Topiramate displays a scavenging capacity
      compared to the reference compound, with the exception of ONOO(-), although it
      was less efficient than nordihydroguaiaretic acid, dimethylthiourea, ascorbic
      acid, sodium pyruvate and glutathione for O2(.-), OH., HOCl, H2O2 and (1)O2(P <
      0.0001), respectively, and not induced significant growth inhibition in cancer
      cell lines. The direct antioxidant properties of topiramate could explain the
      neuroprotective effects attributed to this compound and suggest its use as
      chemopreventive agent in a future.

PMID- 22661104
TI  - Anxiety, depression, and quality of life in German ambulatory breast cancer
      patients.
AB  - BACKGROUND: The aim of the study was to determine the predictors of health
      related quality of life in ambulatory breast cancer patients. METHODS: A total of
      107 breast cancer outpatients were tested with the Hospital Anxiety and
      Depression Scale (HADS) and the quality of life instrument EORTC QLQ-C30.
      Furthermore, the degree of social support and shared decision making (SDM) were
      assessed. RESULTS: In nearly all domains of EORTC QLQ-C30 the patients reported
      worse mean scores than the general population in a clinically significant range,
      especially in the symptom scales. Therapy-related factors and the degree of SDM
      contributed only marginally to quality of life. Social support, however, proved
      to be predictive of better mental health and better quality of life in many
      domains. CONCLUSION: Irrespective of the therapy, the social network of the
      patients should be activated to help the patients to cope with the disease.
      However, the findings do not support the idea that enhanced SDM would have
      beneficial effects on mental health.

PMID- 22661105
TI  - Mother-teacher agreement on preschoolers' symptoms of ODD and CD: does context
      matter?
AB  - The aims of this study were to examine mother-teacher agreement on oppositional
      defiant disorder (ODD) and conduct disorder (CD) symptoms and diagnoses in
      preschool children; to determine if context is a source of disagreement; and to
      explore if sex, referral status, and age moderated agreement rates. Participants
      included 158 male and 139 female 3- to 5-year old preschool children, their
      mothers, and teachers. A structured interview, the Kiddie-Disruptive Behavior
      Disorder Schedule was used for maternal report and teachers completed the Early
      Childhood Inventory. Results indicated that mothers reported more symptoms and
      diagnoses of ODD and CD than teachers, and mother-teacher agreement on both ODD
      and CD symptoms and diagnoses was low. Level of mother-teacher agreement
      increased when reporting on behavior in the same context; however, the rates
      remain modest. Referral status increased the likelihood of mother and teacher
      agreement on several ODD and CD symptoms, as well as ODD and CD diagnosis. These
      data suggest that context plays a role in mother-teacher agreement in the
      assessment of young children's ODD and CD symptoms.

PMID- 22661106
TI  - Semantic language as a mechanism explaining the association between ADHD symptoms
      and reading and mathematics underachievement.
AB  - ADHD is associated with academic underachievement, but it remains unclear what
      mechanism accounts for this association. Semantic language is an underexplored
      mechanism that provides a developmental explanation for this association. The
      present study will examine whether semantic language deficits explain the
      association between ADHD and reading and mathematics underachievement, taking
      into account alternative explanations for associations, including verbal working
      memory (WM) impairments, as well as specificity of effects to inattentive and
      hyperactive-impulsive ADHD symptom domains. Participants in this cross-sectional
      study were 546 children (54 % male) ages six to twelve (M = 9.77, SD = 1.49).
      ADHD symptoms were measured via maternal and teacher report during structured
      interviews and on standardized rating forms. Children completed standardized
      semantic language, verbal WM, and academic testing. Semantic language fully
      mediated the ADHD-reading achievement association and partially mediated the ADHD
      mathematics achievement association. Verbal WM also partially mediated the ADHD
      mathematics association but did not mediate the ADHD-reading achievement
      association. Results generalized across inattentive and hyperactive-impulsive
      ADHD symptom domains. Semantic language explained the association between ADHD
      and reading underachievement and partially explained the association between ADHD
      and mathematics underachievement. Together, language impairment and WM fully
      explained the association between ADHD and reading underachievement, in line with
      developmental models suggesting that language and WM conjointly influence the
      development of attention and subsequent academic achievement. This work has
      implication for the development of tailored interventions for academic
      underachievement in children with ADHD.

PMID- 22661107
TI  - Health-related quality of life among adults with work-related asthma in the
      United States.
AB  - PURPOSE: The objective of this study was to examine health-related quality of
      life among adults with work-related asthma. METHODS: We analyzed 2006-2009
      Behavioral Risk Factor Surveillance System Asthma Call-back Survey data for ever
      employed adults with current asthma from 38 states and District of Columbia.
      Individuals with work-related asthma had been told by a doctor or other health
      professional that their asthma was related to any job they ever had. Health
      related quality of life indicators included poor self-rated health, impaired
      physical health, impaired mental health, and activity limitation. We calculated
      prevalence ratios (PRs) adjusted for age, sex, race/ethnicity, education, income,
      employment, and health insurance. RESULTS: Of ever-employed adults with current
      asthma, an estimated 9.0% had work-related asthma, 26.9 % had poor self-rated
      health, 20.6% had impaired physical health, 18.2% had impaired mental health, and
      10.2% had activity limitation. Individuals with work-related asthma were
      significantly more likely than those with non-work-related asthma to have poor
      self-rated health [PR, 1.45; 95% confidence interval (CI), 1.31-1.60], impaired
      physical health (PR, 1.60; 95% CI, 1.42-1.80), impaired mental health (PR, 1.55;
      95% CI, 1.34-1.80), and activity limitation (PR, 2.16; 95% CI, 1.81-2.56).
      CONCLUSIONS: Future research should examine opportunities to improve health
      related quality of life among individuals with work-related asthma.

PMID- 22661108
TI  - Measurement of individualised quality of life amongst young people with indicated
      personality disorder during emerging adulthood using the SEIQoL-DW.
AB  - PURPOSE: To examine both the feasibility of applying the Schedule for the
      Evaluation of Individual Quality of Life-Direct Weighting procedure (SEIQoL-DW)
      as a routine outcome measure within an early intervention service for young
      people with indicated personality disorder and the overall quality of life (QoL)
      in this population. METHODS: SEIQoL-DW was administered alongside the
      Standardised Assessment of Personality-Abbreviated Scale-Self-Report (SAPAS-SR),
      Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder Scale (GAD-7)
      and the Post-Traumatic Stress Disorder-Primary Care (PTSD-PC) as part of routine
      service evaluation over a 16-month period. Descriptive statistics were calculated
      for data reflecting use of the SEIQoL-DW alongside demographic and outcome
      variables. RESULTS: The SEIQoL-DW was administered to 52 young adults with
      indicated personality disorder, with 47 completing the measure, taking an average
      time of 27 min. Individual QoL was poor with a mean global index score of 55.07
      (SD = 22.34). Individual QoL areas formed five main domains-'Aspects of Daily
      Living', 'Relationships', 'Social Life and Leisure', 'Family' and 'Emotional and
      Physical Wellbeing'. CONCLUSION: This study further extends the application of
      the SEIQoL-DW for use as a routine outcome measure within a busy service setting,
      although ways to accommodate administration time need to be considered. Poor QoL
      highlights the need for continued development of services to meet the needs of
      young adults with indicated personality disorder.

PMID- 22661109
TI  - Simultaneous aortic valve replacement in left ventricular assist device
      recipients: single-center experience.
AB  - INTRODUCTION: Aortic valve regurgitation or the presence of a mechanical aortic
      valve prosthesis is a relative contraindication for implantation of left
      ventricular assist devices (LVAD). However, concomitant aortic valve replacement
      by a biological prosthesis is one of the options in this situation. We analyzed
      our recent experience with left ventricular assist device implantation and
      concomitant aortic valve replacement. METHODS: Between January 1, 2008 and
      January 15, 2012, 318 adult patients (>18 years old) were supported with a long
      term implantable LVAD in our institution. In 19, simultaneous aortic valve
      replacement (6 redo and 13 primary procedures) was performed. Patients were
      divided into 2 groups according to INTERMACS (IM) level: Group 1 (n = 7)
      consisted of patients with IM level 1-2 and Group 2 (n = 12) of IM level 3-4
      patients. As a control cohort we analyzed all LVAD recipients during the study
      period (n = 299, study group excluded). The control cohort was similarly divided
      into two groups according to the IM level: Group 3 (n = 162) consisted of
      patients with IM level 1-2 and Group 4 (n = 137) of those with IM level 3-5.
      Perioperative data and outcomes in all groups were retrospectively analyzed and
      compared (Group 1 compared to Group 3; and Group 2 to Group 4). RESULTS: In study
      Groups 1 and 2 all patients were male; in Groups 3 and 4, 80% and 88%
      respectively were male. Median age distribution in Groups was 55, 61, 54, and 57
      years respectively. Patients from Group 2 were significantly older than those
      from Group 4 (p = 0.039). Body mass index was significantly lower in Group 1 than
      in Group 3 (p = 0.033). Cardio-pulmonary bypass time was significantly longer in
      Groups 1 and 2 compared with Groups 3 and 4 respectively (p=0.001). Patients from
      Group 1 had a trend more often to develop right ventricular failure requiring a
      right ventricular assist device (RVAD) than those in Group 3 (p = 0.09).
      Intensive care unit stay duration of mechanical ventilation and in-hospital
      mortality in Group 1 were significantly higher than in Group 3 (p = 0.025, p =
      0.005, p = 0.038). Patients from Group 2 had similar outcomes compared to those
      from Group 4. CONCLUSIONS: In stable patients, simultaneous aortic valve
      replacement and LVAD implantation are not associated with an impaired outcome. In
      patients with cardiogenic shock an additional aortic valve replacement may impair
      outcome; therefore alternative techniques should be considered.

PMID- 22661110
TI  - An exploratory study of sleep quality, daytime function, and quality of life in
      patients with mechanical circulatory support.
AB  - PURPOSE: To identify and describe: (1) characteristics of sleep quality, daytime
      sleepiness, and quality of life (QOL) pre and post implantation of a left
      ventricular assist device (LVAD); (2) changes in sleep quality, daytime
      sleepiness, and QOL at baseline and 6 months post implant; and (3) relationships
      among the sleep quality, daytime sleepiness, and QOL variables. METHODS: We
      employed an exploratory research design. Fifteen patients with continuous/non
      pulsatile flow LVAD consented to partake in the study. However, only 12 patients
      completed the baseline and 6-month post-LVAD implant data. We used the Pittsburgh
      Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Minnesota Living
      with Heart Failure Questionnaire (MLHFQ) to measure study variables. Data were
      analyzed using IBM SPSS 19.0 software. RESULTS: Patients reported worse sleep
      quality accompanied by daytime sleepiness particularly at baseline, and
      persisting up to 6 months post LVAD implant. A significant improvement in QOL was
      observed at 6 months post implant, but remained at poor levels. Correlations
      among sleep disturbance and daytime dysfunction components of PSQI and global
      daytime sleepiness (ESS) with QOL were strong (Pearson's correlations r >.60; p
      values < .05). CONCLUSIONS: We report the first empirical data describing the
      characteristics and correlations among sleep quality, daytime sleepiness, and QOL
      in patients with LVADs. Our findings offer beginning evidence about the sleep-QOL
      connection in this population which warrants attention in clinical practice and
      research. Further research is required to clearly elucidate these phenomena in
      patients with mechanical circulatory support and other implantable artificial
      organs.

PMID- 22661111
TI  - Low-dose continuous renal replacement therapy for acute kidney injury.
AB  - BACKGROUND: Continuous renal replacement therapy (CRRT) is used increasingly to
      treat acute kidney injury (AKI), which is a common condition in the intensive
      care unit (ICU). However, the optimal CRRT dose for the treatment of AKI is still
      a matter of controversy. This study was conducted to ascertain the minimal dose
      of CRRT that can be effective on AKI patient outcomes. METHODS: This was a
      retrospective observational study in two ICUs of academic medical centers in
      Japan. Patients aged 15 years or older admitted to the ICUs from January 2007 to
      July 2010 and treated with CRRT for AKI during their ICU stay were included. Data
      were retrospectively collected from patient records. Patients were categorized by
      doses that were above (higher-dose group) or below (lower-dose group) the median.
      Major outcome measures were hospital mortality, ICU mortality, and renal recovery
      at hospital discharge. RESULTS: 131 AKI patients were treated with continuous
      veno-venous hemodiafiltration (CVVHDF) during the study period. The median dose
      of CVVHDF was 16 ml/kg per hr (IQR = 14 to 20). Hospital mortality was 44%, which
      was significantly lower than the predicted mortality (56%, p<0.01). Patients who
      received lower-dose CRRT tend to have lower mortality rates (36% vs. higher-dose
      53%; p = 0.055). CONCLUSIONS: We found that low-dose CRRT did not increase
      mortality in critically ill patients with AKI. We also found that AKI patients
      treated with lower-dose CRRT non-significantly but numerically lower hospital
      mortality compared to higher-dose CRRT.

PMID- 22661112
TI  - Twisted cardiovascular cages for intravascular axial flow blood pumps to support
      the Fontan physiology.
AB  - Failing single ventricle physiology represents an ongoing challenge in mechanical
      assist device development, requiring pressure augmentation in the cavopulmonary
      circuit, reduction of systemic venous pressure, and increased cardiac output to
      achieve hemodynamic stabilization. To meet these requirements, we are developing
      a percutaneously-placed, axial flow blood pump to support ailing single ventricle
      physiology in adolescents and adults. We have modified the outer cage of the
      device to serve as both a protective and functional design component. This study
      examined the performance of 3 cage geometries with varying directions of filament
      twist using numerical simulations and hydraulic experiments. All 3 cage and pump
      models performed in acceptable ranges to support Fontan patients. The cage design
      employing filaments that are twisted in the opposite direction to the impeller
      blades and in the direction of the diffuser blades (against-with) demonstrated
      superior performance by generating a pressure rise range of 5-38 mmHg of flow
      rates of 0.5-6 l/min at rotational speeds of 5000-7000 rpm. The blood damage
      indices for all of the cages were found to be well below 2%, and the scalar
      stress levels were below 200 Pa. This study represents ongoing progress in the
      development of the impeller and cage assembly. Validation of the results will
      continue in experiments with blood bag evaluation as well as by particle image
      velocimetry measurements.

PMID- 22661113
TI  - The Sorin freedom stentless pericardial valve: clinical and echocardiographic
      performance at 10 years.
AB  - OBJECTIVE: The Sorin Pericarbon Freedom (SPF) is a stentless valve made of
      pericardium clinically available in 1990. We report the clinical and hemodynamic
      performance of the SPF at 10 years. METHODS: From April 2000 to December 2005, 85
      patients with a mean age of 75 +/- 6 years (range 57-86), underwent aortic valve
      replacement (AVR) with an SPF. Mean left ventricular ejection fraction was 58 +/-
      10% (range 29-86%) and mean peak transvalvular gradient (PG) 86 +/- 24 mmHg.
      Clinical evaluation was performed at 3, 6, 12 months, and yearly thereafter.
      RESULTS: There were 2 operative deaths (2.4%). Follow-up ranged from 2 to 135
      months (mean 78 +/- 32 months) and was 99% complete. There were 35 late deaths, 7
      of which were valve-related, with an actuarial survival of 45 +/- 8% at 10 years.
      Structural SPF deterioration occurred in 2 patients, with an actuarial freedom of
      96 +/- 3%. A total of 4 patients were re-operated, 2 because of structural
      deterioration, 1 because of endocarditis, and 1 because of sinotubular junction
      dilatation; freedom from reoperation was 93 +/- 4% at 10 years. At last clinical
      control, 41 patients (89%) were in NYHA class I or II. Mean SPF effective orifice
      area varied from 1.55 +/- 0.66 cm2 for size 21 mm to 2.33 +/- 0.86 cm2 for size
      27 mm; PG varied from 19 +/- 10 mmHg for size 21 mm to 11 +/- 6 mmHg for size 27
      mm. Left ventricular mass index decreased from 213 +/- 51 gm/m2 to 157 +/- 436
      gm/m2 (p<0.001). CONCLUSIONS: The SPF has demonstrated overall good results in
      terms of valve durability and freedom from valve-related complications up to 10
      years, with excellent hemodynamic performance.

PMID- 22661115
TI  - Modelling of axonal cargo rerouting in a dendrite.
AB  - This paper develops a model of axonal cargo transport in and out of a dendrite en
      route to the axon. The entrance of axonal cargos into a dendrite is explained by
      a mixed orientation of microtubules (MTs) in a dendrite. Using the simplest
      hypothesis explaining cargo targeting to axons and dendrites (this hypothesis
      postulates that axonal cargos are driven by kinesin motors and that dendritic
      cargos are driven by dynein motors), it is assumed that axonal cargos can enter a
      dendrite using MTs whose plus-ends are directed outward. Later, as kinesin motors
      detach from these MTs and reattach to oppositely directed MTs, the axonal cargos
      are transported out of the dendrite and are rerouted to the axon. The developed
      model makes it possible to investigate the dynamics of axonal cargo trafficking
      in a dendrite and study how it is affected by various input parameters, such as
      the kinesin velocity distribution. 

PMID- 22661116
TI  - Measurement of chondrocyte chemotaxis using a Boyden chamber: a model of receptor
      mediated cell migration combined with cell sedimentation.
AB  - The Boyden chamber assay measures the coefficients of cell motility by fitting
      the experiments with theoretical calculations. Under the circumstance of rapid
      receptor kinetics, the distribution of chemical-receptor complexes on the cell
      surface can be treated as being quasi-steady and chemotaxis is directly related
      to the biochemical concentration, leading to the celebrated Keller-Segel model,
      which has been shown to be an approximation to the full receptor-mediated form.
      No matter approximate or full, these approaches have ignored cell sedimentation
      in the upper chamber, assuming that all the cells have already resided on the
      filter top at the beginning of the test. However, the time required for all the
      cells to settle through the suspension can be close to the entire incubation time
      of just several hours. In order to amend such a deficiency, the present work
      combines the receptor-based model with cell sedimentation for modeling the
      chemotaxis assay using the Boyden chamber. Simulations were performed to fit the
      experimental data in the literature, which tested the chondrocyte chemotactic
      motility in response to collagen. Results show that once cell sedimentation is
      involved, the assumption of quasi-steady receptor distribution may be invalid for
      the Boyden assay. This is because the formation of the chemical-receptor
      complexes is profoundly retarded by the process of cell sedimentation. To
      estimate the parameters of cell motility and receptor kinetics, cell
      sedimentation should be incorporated in modeling the chemotaxis assay using the
      Boyden chamber. 

PMID- 22661118
TI  - Assessment of post-thawed ram sperm viability after incubation with seminal
      plasma.
AB  - A suggested alternative to improve post-thawed ram semen quality is the addition
      of seminal plasma (SP). This is thought to be capable of improving sperm
      resistance to thermal shock, reverting cryocapacitation and helping sperm
      survival. The aim of this study was to evaluate the effect of frozen-thawed ram
      semen incubation with SP on mitochondrial activity, acrosomal membrane integrity,
      necrosis and apoptosis. Frozen/thawed semen was divided into two groups: the SP
      Group and the control group. After 0, 30 and 60 min, fluorescent probes were
      added to aliquots from each treatment group and evaluated using flow cytometry.
      There was no difference between treatment groups in almost all viability
      parameters evaluated, with exception of the apoptosis, which was found increased
      in SP group. The increase in incubation period resulted in a decreased percentage
      of sperm with high mitochondrial membrane potential and acrosomal membrane
      integrity and an increased percentage of necrotic and apoptotic sperm cells. In
      conclusion, the present study showed that addition of seminal plasma after
      thawing cryopreserved ram sperm had no identifiable beneficial effect on sperm
      quality.

PMID- 22661117
TI  - Centrosome amplification and chromosomal instability in human and animal
      parthenogenetic cell lines.
AB  - Parthenotes have been proposed as a source of embryonic stem cells but they lack
      the centriole which is inherited through the sperm in all mammalian species,
      except for rodents. We investigated the centrosome of parthenotes and
      parthenogenetic embryonic stem cells using parthenogenetic and biparental pig pre
      implantation embryos, human and pig parthenogenetic and biparental embryonic stem
      cells, sheep fibroblasts derived from post implantation parthenogenetic and
      biparental embryos developed in vivo. We also determined the level of aneuploidy
      in parthenogenetic cells. Oocytes of all species were activated using ionomycin
      and 6-dimethylaminopurine (6-DMAP). Over 60% of parthenogenetic blastomeres were
      affected by an excessive number of centrioles. Centrosome amplification, was
      observed by microscopical and ultrastructural analysis also in parthenogenetic
      cell lines of all three species. Over expression of PLK2 and down regulation of
      CCNF, respectively involved in the stimulation and inhibition of centrosome
      duplication, were present in all species. We also detected down regulation of
      spindle assembly checkpoint components such as BUB1, CENPE and MAD2. Centrosome
      amplification was accompanied by multipolar mitotic spindles and all cell lines
      were affected by a high rate of aneuploidy. These observations indicate a link
      between centrosome amplification and the high incidence of aneuploidy and suggest
      that parthenogenetic stem cells may be a useful model to investigate how
      aneuploidy can be compatible with cell proliferation and differentiation.

PMID- 22661120
TI  - Attitudes toward violence scale: psychometric properties with a high school
      sample.
AB  - Youth violence represents a serious problem affecting individuals, communities,
      and the larger society. Greater efforts aimed at the eradication of youth
      violence are necessary, and work in this field could be enhanced by
      psychometrically strong measures. The present study examined the factor structure
      of the Attitudes Toward Violence Scale (ATV) using exploratory factor analysis
      (EFA) with a sample of 359 high school students. A three-factor structure was
      identified. The three factors were invariant across sex, however, males obtained
      significantly higher scores on the three ATV factors and on the ATV total score
      showing generally moderate effect sizes. Directions for future research with the
      ATV are discussed.

PMID- 22661119
TI  - Sunlight exposure and cutaneous human papillomavirus seroreactivity in basal cell
      and squamous cell carcinomas of the skin.
AB  - BACKGROUND: Ultraviolet radiation exposure may interact synergistically with
      cutaneous human papillomavirus (HPV) infection in the development of basal cell
      carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin. METHODS: To
      investigate differences in the risk of sunlight-associated BCC and SCC by
      cutaneous genus-specific HPV serostatus, a case-control study was conducted among
      204 BCC and 156 SCC cases who were recruited from a university dermatology clinic
      and 297 controls who had no history of cancer and screened negative for current
      skin cancer. Logistic regression was used to calculate odds ratios (ORs) and 95%
      confidence intervals (CIs) for the associations between measures of sunlight
      exposure and BCC/SCC, stratified by genus-specific HPV serostatus, with
      adjustment for age and sex. RESULTS: Sunburn due to cutaneous sensitivity to
      sunlight exposure (P = .006) and poor tanning ability (P = .003) were associated
      with a higher seroprevalence for genus beta HPV types. Poor or no tanning ability
      was more strongly associated with SCC among individuals who were seropositive for
      antibodies to cutaneous HPV types in genera alpha (OR, 15.60; 95% CI, 5.40-45.1;
      P = .01 for interaction) and beta (OR, 6.86; 95% CI, 3.68-12.80; P = .001 for
      interaction), compared with individuals who were seronegative for these HPV
      types. CONCLUSIONS: Seropositivity for HPV types in genera alpha or beta
      increased the risk of SCC associated with poor tanning ability.

PMID- 22661121
TI  - Risk and protective factors for physical and emotional intimate partner violence
      against women in a community of lima, peru.
AB  - This article shows risk and protective factors for both physical and emotional
      intimate partner violence (IPV) against women. The study was carried out in a
      shanty town of Lima, Peru, which has a strong community organization. One hundred
      ninety-two women between 25 and 59 years old (M = 34.09, SD = 6.5) were
      interviewed; 44.3% had secondary education, 75.5% were housewives, and 94% lived
      with their partner. The measurement instrument was a survey especially developed
      for this project to explore occurrence of physical and emotional IPV and to
      identify factors associated with them; factors were classified in individual and
      relational levels according to the ecological nested model (ENM). A logistic
      regression analysis was used to test the associations; the results showed that
      for emotional IPV, men's assertiveness was a protective factor, whereas their
      emotional instability and jealousy were risk factors. For physical IPV, there
      were no identified risks or protective factors. These results are presented and
      discussed.

PMID- 22661122
TI  - Factors associated with the sexual assault of students: an exploratory study of
      victims treated at hospital-based sexual assault treatment centers.
AB  - Research suggests that students experience high levels of sexual assault, but
      studies addressing how they differ in their experiences from other sexual assault
      victims are virtually nonexistent. To address this gap, information was collected
      from consecutive individuals, aged 16 years or older, presenting to one of 7
      hospital-based sexual assault treatment centers in Ontario from 2005 to 2007. Of
      the 882 victims seen during the study period, 32% were students. Relative to
      other sexual assault victims, students were more likely to be aged 16 to 18 years
      and 19 to 24 years versus 25 years and older. They were more likely to be living
      alone, with family of origin, a partner or spouse, or a nonrelative than on the
      street or in a shelter or institution. They were also more likely to report
      having consumed over-the-counter medication in the 72 hours prior to examination.
      Student victims were less likely than nonstudent victims to report having a
      disability and having used street drugs. Implications for research, education,
      and practice are discussed.

PMID- 22661124
TI  - Reply to: Increased prevalence of sarcoidosis in Ireland.

PMID- 22661123
TI  - Effects of dose ranging of adenosine infusion on electrocardiographic findings
      during and after general anesthesia.
AB  - PURPOSE: To assess changes in the electrocardiogram (ECG) associated with
      intraoperative infusion of adenosine in patients undergoing open abdominal
      gynecological surgery. METHODS: One hundred and sixty-six patients undergoing
      gynecological surgery were randomly assigned to receive one of four doses of
      adenosine infusion (25, 50, 100, or 200 MUg/kg/min) or matching placebo. Study
      drug administration was started at skin incision and discontinued at end of
      surgery. A standardized general anesthetic regimen was used and adjusted based on
      hemodynamic and bispectral index values. Heart rate and rhythm variables, and PR,
      QRS, QT, and QTc intervals were recorded from 12-lead ECGs before anesthesia and
      immediately after patient arrival in the postanesthesia care unit. In addition, a
      rhythm strip was obtained during administration of the loading dose of the study
      drug. ECG variables were compared within and between groups. Incidence of ECG and
      hemodynamic abnormalities was recorded. RESULTS: One hundred and fifty-one
      subjects had a full set of electrocardiographic data: placebo (n = 38), group
      adenosine 25 MUg/kg/min (n = 31), group adenosine 50 MUg/kg/min (n = 29), group
      adenosine 100 MUg/kg/min (n = 28), and group adenosine 200 MUg/kg/min (n = 25).
      Statistically significant postoperative QTc prolongation was observed in all
      study groups when compared with baseline except for the adenosine 200 MUg/kg/min
      group. However, these changes from baseline were not different among the groups.
      There were also no significant differences in PR, QRS, and QT intervals between
      the treatment groups. CONCLUSION: There was no difference in QTc prolongation
      following intraoperative administration of adenosine infusion compared with
      placebo during isoflurane general anesthesia. However, QTc prolongation is common
      following general anesthesia.

PMID- 22661125
TI  - Clinical implication of extended-spectrum cephalosporin nonsusceptibility in
      Streptococcus pneumoniae meningitis.
AB  - The clinical implication of extended-spectrum cephalosporin (ESC) resistance has
      been unclear in patients with Streptococcus pneumoniae meningitis (SPM). We
      collected the clinical data of 120 patients with SPM in 12 hospitals of the
      Republic of Korea. The clinical characteristics and outcomes of 23 ESC
      nonsusceptible SPM episodes were compared to those of 97 ESC-susceptible
      episodes. Hospital acquisition, presence of other foci of pneumococcal infection,
      septic shock at initial presentation, or concomitant bacteremia were more
      commonly observed in ESC-nonsusceptible than ESC-susceptible SPM. Empiric
      antimicrobial therapy with vancomycin and ESC combination was very common in both
      groups. Although there was a tendency towards higher early fatality in ESC
      nonsusceptible SPM (3-day mortality; 17.4 % vs. 4.4 %, p = 0.05), in-hospital
      mortality (26.1 % vs. 20.9 %, p = 0.59) and median length of hospital stay (20
      days vs. 24 days, p = 0.34) did not differ between ESC-nonsusceptible and ESC
      susceptible SPM.

PMID- 22661126
TI  - Object recognition as a measure of memory in 1-2 years old transgenic minipigs
      carrying the APPsw mutation for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a disabling, fatal disease, where animal models
      potentially can enable investigation of aetiology and treatment. The first litter
      of Gottingen minipigs carrying a mutation for human AD was born in 2007, showing
      transgene expression. In human AD patients, memory impairment is the most
      striking and consistent feature. The aim of the present study was to examine
      effects of the APPsw transgene on memory of AD minipigs compared with non
      transgenic controls at two ages (1-2 years) using the spontaneous object
      recognition test (SORT), which is based on behavioural discrimination of familiar
      and novel objects. No significant difference between AD minipigs and controls was
      found when comparing object recognition as a measure of memory. The minipigs did
      explore the novel object significantly more than the familiar, indicating the
      expected recognition of the familiar object. Two different inter-phase intervals
      were used (IPI: 10-40 min). For both ages, object recognition was evident using
      10 min IPI. When using 40 min IPI, object recognition was evident only at age 1
      year. Comparing memory of a relatively small group of AD minipigs and controls at
      two rather young ages using the SORT, we were not able to show memory impairment
      in APPsw carrying minipigs. Being an age-dependent disease, the transgene is
      expected to cause AD-like symptoms in this porcine model, and the SORT should be
      repeated at older ages.

PMID- 22661127
TI  - A biomechanical assessment of the sliding motion of curling delivery in elite and
      subelite curlers.
AB  - The present study examined the technical characteristics of sliding performance
      from push-off until stone release in curling delivery. Five elite performance
      level curlers (> 7 years experience) and five subelite level curlers (< 3 years
      experience) were analyzed during the action of delivery of a curling stone. The
      joint angles, angular velocities, and moments of the body center of mass (COM)
      were determined based on three-dimensional kinematic data. The plantar pressure
      data were measured using a validated in-shoe system. The results indicated that
      the gliding time and horizontal velocity of the mass center of the body during
      the sliding phase were not significantly different between the elite and subelite
      groups. However, there were significant differences in the gliding distance and
      the rate of changes in velocity profiles of body COM between the two groups. The
      moment of the body COM from its relative position to the ankle of the support
      limb in the anterior/posterior direction was positive in elite curlers and
      negative in subelite curlers. In addition, larger ankle dorsiflexion and greater
      contact area of the sliding foot were observed in elite curlers. These data
      suggest a superior ability of elite curlers to maintain a regulated movement
      speed and balance control during the performance of a curling stone delivery.

PMID- 22661128
TI  - Historical milestones in renal pathology.

PMID- 22661129
TI  - Characterization of serous retinal detachments in uveitis patients with optical
      coherence tomography.
AB  - OBJECTIVES: To determine the prevalence of serous retinal detachments (SRD) using
      optical coherence tomography (OCT) in a large database of patients with uveitis
      from a tertiary referral setting, to describe clinical features of patients with
      SRD, and to ascertain retinal architectural features found in association with
      SRD. MAIN OUTCOME MEASURES: Prevalence of SRD in uveitis patients imaged with
      OCT, correlation of visual acuity with SRD, anatomic subtypes of uveitis
      identified, and association of SRD with various subtypes of macular edema (focal
      and diffuse) and retinal architectural abnormalities. DESIGN: Retrospective,
      single-setting cross-sectional study of all OCTs in a digital imaging base
      ordered on patients from a tertiary referral uveitis clinic between July 2006 and
      March 2008. RESULTS: SRD were identified in 17 of 111 uveitis patients (15 %)
      reviewed; bilateral SRD were found in 5 of 17 patients (29 %). Intermediate
      uveitis was the most common disease association (47 %), but other conditions
      identified included Vogt-Koyanagi-Harada syndrome, multifocal
      choroiditis/panuveitis, and sarcoidosis. Retinal architectural features
      identified in association with SRD included focal macular edema (59 %), diffuse
      macular edema (50 %), any intraretinal edema (77 %), both diffuse and focal
      macular edema (32 %), and retinal pigment epithelial alteration (27 %). Moderate
      or severe visual impairment, defined as visual acuity 20/50 or poorer was seen in
      71 % of patients with SRD. Poorer visual acuity was correlated with increased
      central subfield thickness in patients with SRD (r (2) = 0.41, p < 0.001).
      CONCLUSION: SRD were present in 15 % of the uveitis patients reviewed. Moderate
      to severe vision impairment was present in the majority of eyes (71 %) with SRD.
      Diffuse macular edema and focal cystoid macular edema were the OCT features most
      commonly associated with SRD. Intermediate and panuveitis were the most common
      anatomic sites of inflammation. A variety of pathogenic mechanisms, both
      inflammatory and non-inflammatory, may be involved in SRD in uveitis patients;
      identification of the precise mechanism is important for appropriate therapy.

PMID- 22661131
TI  - Why another conference on personalized medicine?

PMID- 22661130
TI  - Derivation, culture and retinal pigment epithelial differentiation of human
      embryonic stem cells using human fibroblast feeder cells.
AB  - PURPOSE: Retinal pigment epithelium cells derived from human embryonic stem cells
      (ESCs) could be useful for restoring retinal function in age-related macular
      degeneration. However the use of non-human feeder cells to support the growth of
      ESCs for clinical applications raises the concern of possible contamination
      because of direct contact between animal and human cells. METHODS: In this study,
      we produced human ESCs using human fibroblast feeder layers isolated from
      foreskin and abdominal tissues. Using this system, human ESCs differentiated into
      retinal pigment epithelium cells in differentiation medium. RESULTS: Seven human
      ESC lines were established from 18 blastocysts. These human ESCs showed normal
      morphology, expressed all expected cell surface markers, had the ability to form
      embryoid bodies upon culture in vitro and teratomas after injection into SCID
      mice, and differentiated further into derivatives of all three germ layers. Under
      conditions of committed differentiation, these human ESCs could differentiate
      into retinal pigment epithelium cells after 2 months in culture. CONCLUSIONS: The
      results of this study demonstrated that human foreskin/abdominal fibroblasts have
      the potential to support the derivation and long-term culture of human ESCs,
      which can then be used to generate retinal pigment epithelium cells with
      characteristic morphology and molecular markers. This technique avoids the
      concerns of contamination from animal feeder layers during human ESC derivation,
      culture and differentiation, and will thus facilitate the development of retinal
      pigment epithelium cell transplantation therapy.

PMID- 22661132
TI  - The promise and challenge of personalized medicine: aging populations, complex
      diseases, and unmet medical need.
AB  - The concept of personalized medicine is not new. It is being discussed with
      increasing interest in the medical, scientific, and general media because of the
      availability of advanced scientific and computational technologies, and the
      promise of the potential to improve the targeting and delivery of novel
      medicines. It is also being seen as one approach that may have a beneficial
      impact on reducing health care budgets. But what are the challenges that need to
      be addressed in its implementation in the clinic? This article poses some
      provocative questions and suggests some things that need to be considered.

PMID- 22661133
TI  - Personalized medicine--a tailored health care system: challenges and
      opportunities.
AB  - The vision of the future health care should be a system in which patient care is
      consistently improved through the use of information on the individual patient's
      genomes and their downstream products. This requires the exploration of strategic
      relationships among various disciplines such as life sciences, mathematics,
      physics, chemistry, and information and communication technology, and
      constellation thinking to propose new ways for the diagnosis and therapy of
      diseases, integrated with a planned trans-disciplinary scientific approach
      involving all interested parties. Connecting high-quality trans-disciplinary
      scientists on a pan-European level through programs such as the Cooperation in
      Science and Technology (COST) can support capacity building and increase the
      impact of personalized medicine research on regulatory bodies, decision makers,
      pharmaceutical and insurance companies, and the paying public. Such group effort
      could enable breakthrough scientific developments leading to new concepts and
      products and thereby contributing to the strengthening of Europe's research and
      innovation capacity while reforming the health care system.

PMID- 22661134
TI  - The involvement of noradrenergic mechanisms in the suppressive effects of
      diazepam on the hypothalamic-pituitary-adrenal axis activity in female rats.
AB  - AIM: To elucidate the involvement of noradrenergic system in the mechanism by
      which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis
      activity. METHODS: Plasma corticosterone and adrenocorticotropic hormone (ACTH)
      levels were determined in female rats treated with diazepam alone, as well as
      with diazepam in combination with clonidine (alpha(2)-adrenoreceptor agonist),
      yohimbine (alpha(2)-adrenoreceptor antagonist), alpha-methyl-p-tyrosine (alpha
      MPT, an inhibitor of catecholamine synthesis), or reserpine (a catecholamine
      depleting drug) and yohimbine. RESULTS: Diazepam administered in a dose of 2.0
      mg/kg suppressed basal HPA axis activity, ie, decreased plasma corticosterone and
      ACTH levels. Pretreatment with clonidine or yohimbine failed to affect basal
      plasma corticosterone and ACTH concentrations, but abolished diazepam-induced
      inhibition of the HPA axis activity. Pretreatment with alpha-MPT, or with a
      combination of reserpine and yohimbine, increased plasma corticosterone and ACTH
      levels and prevented diazepam-induced inhibition of the HPA axis activity.
      CONCLUSION: The results suggest that alpha(2)-adrenoreceptors activity, as well
      as intact presynaptic noradrenergic function, are required for the suppressive
      effect of diazepam on the HPA axis activity.

PMID- 22661135
TI  - Endocrinological outcomes of pure endoscopic transsphenoidal surgery: a Croatian
      Referral Pituitary Center experience.
AB  - AIM: To analyze early remission, complications, and pituitary function recovery
      after pure endoscopic endonasal transsphenoidal surgery (PEETS), a novel method
      in pituitary adenoma treatment. METHODS: Testing of all basal hormone values and
      magnetic resonance imaging (MRI) were performed preoperatively and
      postoperatively (postoperative MRI only in nonfunctioning adenomas) in 117
      consecutive patients who underwent PEETS in the period between 2007 and 2010. The
      series consisted of 21 somatotroph adenomas, 61 prolactinomas, and 4 corticotroph
      and 31 nonfunctioning adenomas. Sixty-three were macroadenomas and 54 were
      microadenomas. Remission was defined as hormonal excess normalization on the
      seventh postoperative day in functioning adenomas and as normal MRI findings
      approximately four months postoperatively in nonfunctioning adenomas. The
      presence of hypogonadism, growth hormone deficiency, and hypothyroidism was
      assessed on the seventh postoperative day. Hypocortisolism was assessed through
      necessity for replacement therapy within 18 months postoperatively. RESULTS:
      Remission was achieved in 84% of patients: in 100% of microadenoma and 70% of
      macroadenoma patients (P<0.001, odds ratio [OR], 28.16, 95% confidence interval
      [CI], 1.61-491.36), respectively. Endocrinological complications occurred in
      17.1% of patients: in 9% of microadenoma and 24% of macroadenoma patients
      (P=0.049, OR, 3.06; 95% CI, 1.03-9.08). Duration of empirical hydrocortisone
      replacement therapy was significantly shorter in microadenoma patients (P<0.001).
      Thirty-five percent of preoperatively present hormonal deficiencies improved
      after the surgery. Between tumor types there were no significant differences in
      remission, complications, and normal pituitary function recovery. CONCLUSION:
      Patients with microadenomas had higher remission and lower complication rates
      following PEETS, emphasizing the necessity for early detection and treatment of
      pituitary adenomas. PEETS is a discussion-worthy method for microprolactinoma
      treatment.

PMID- 22661136
TI  - Lamellar body count as a diagnostic test in predicting neonatal respiratory
      distress syndrome.
AB  - AIM: To determine the lamellar body count (LBC) cutoff value for fetal lung
      maturity and to evaluate the clinical usefulness of LBC in predicting the
      severity of neonatal respiratory distress syndrome (RDS). METHODS: A prospective
      study was conducted from 2002 until 2010. LBC was estimated in uncentrifugated
      amniotic fluid samples using Cell-Dyn 1800 analyzer. Amniotic fluid samples were
      obtained by amniocentesis or by puncturing embryonic membranes during cesarean
      section. The presence of mild, moderate, and severe RDS was assessed by
      neonatologist. RESULTS: A total of 313 patients with singleton pregnancies (24-41
      weeks) were included in the study and 294 met the inclusion criteria. RDS was
      diagnosed in 28 neonates - mild in 8, moderate in 10, and severe in 10. In
      premature neonates (<37 gestational weeks), significant differences in LBC were
      only found between the subgroup without RDS and the group with moderate and the
      group with severe RDS (P<0.001). In all neonates, significant differences were
      found between neonates without RDS and neonates with RDS. Using LBC cutoff value
      of >=20,000/uL, sensitivity, specificity, and positive and negative predictive
      values of LBC in determining mature fetal lungs were 96%, 88%, 45.6%, and 99.5%,
      respectively. CONCLUSION: This study suggests that LBC cutoff value of
      >=20,000/uL can predict pulmonary maturity and reduce the risk of neonatal
      respiratory distress syndrome.

PMID- 22661137
TI  - Increasing prevalence of breast cancer among Saudi patients attending a tertiary
      referral hospital: a retrospective epidemiologic study.
AB  - AIM: To determine the pattern of breast diseases among Saudi patients who
      underwent breast biopsy, with special emphasis on breast carcinoma. METHODS: A
      retrospective review was made of all breast biopsy reports of a mass or lump from
      male and female patients seen between January 2001 and December 2010 at the King
      Khalid University Hospital, Riyadh, Saudi Arabia. RESULTS: Of 1035 breast tissues
      reviewed, 939 specimens (90.7%) were from female patients. There were 690 benign
      (65.8%) and 345 (34.2%) malignant cases. In women, 603 (64.2%) specimens were
      benign and 336 (35.8%) were malignant. In men, 87 specimens (90.6%) were benign
      and 9 (9.4%) were malignant. All malignant cases from male patients belonged to
      invasive ductal carcinoma and the majority of malignant cases from female
      patients belonged to invasive/infiltrating ductal carcinoma. The proportion of
      malignancy was 18% in patients younger than 40 years and 63.2% in patients older
      than 60 years. The mean age of onset for malignancy was 48.6 years. The annual
      percentage incidence of malignant breast cancer steadily increased by 4.8%, from
      an annual rate of 23.5% in 2000 to 47.2% in 2007. CONCLUSION: Among Saudi
      patients, there is a significant increase in the incidence of breast cancer,
      which occurs at an earlier age than in western countries. Continued vigilance,
      mammographic screening, and patient education are needed to establish early
      diagnosis and perform optimal treatment.

PMID- 22661138
TI  - Parental involvement in the war in Croatia 1991-1995 and suicidality in Croatian
      male adolescents.
AB  - AIM: To investigate the association between parental war involvement and
      different indicators of psychosocial distress in a community sample of early
      adolescents ten years after the war in Croatia 1991-1995. METHODS: A total of 695
      adolescents were screened with a self-report questionnaire assessing parental war
      involvement, sociodemographic characteristics, and alcohol and drug consumption.
      Personality traits were assessed with the Junior Eysenck Personality
      Questionnaire; depressive symptoms with the Children's Depression Inventory
      (CDI); and unintentional injuries, physical fighting, and bullying with the World
      Health Organization survey Health Behavior in School-aged Children. Suicidal
      ideation was assessed with three dichotomous items. Suicidal attempts were
      assessed with one dichotomous item. RESULTS: Out of 348 boys and 347 girls who
      were included in the analysis, 57.7% had at least one veteran parent. Male
      children of war veterans had higher rates of unintentional injuries (odds ratio
      [OR], 1.2; 95% confidence interval [CI], 0.56 to 2.63) and more frequent
      affirmative responses across the full suicidal spectrum (thoughts about death -
      OR, 2.1; 95% CI, 1.02 to 4.3; thoughts about suicide - OR, 5; 95% CI, 1.72 to
      14.66; suicide attempts - OR, 3.6; 95% CI, 1.03 to 12.67). In boys, thoughts
      about suicide and unintentional injuries were associated with parental war
      involvement even after logistic regression. However, girls were less likely to be
      affected by parental war involvement, and only exhibited signs of psychopathology
      on the CDI total score. CONCLUSION: Parental war involvement was associated with
      negative psychosocial sequels for male children. This relationship is possibly
      mediated by some kind of identification or secondary traumatization. Suicidality
      and unintentional injuries are nonspecific markers for a broad range of
      psychosocial distresses, which is why the suggested target group for preventive
      interventions should be veteran parents as vectors of this distress.

PMID- 22661139
TI  - Socioeconomic inequalities, health damaging behavior, and self-perceived health
      in Serbia: a cross-sectional study.
AB  - AIM: To analyze the association of socioeconomic factors with self-perceived
      health in Serbia and examine whether this association can be partly explained by
      health behavior variables. METHODS: We used data from the 2007 Living Standards
      Measurement Study for Serbia. A representative sample of 13831 persons aged >=20
      years was interviewed. The associations between demographic factors (age, sex,
      marital status, and type of settlement), socioeconomic factors (education,
      employment status, and household consumption tertiles), and health behavior
      variables (smoking, alcohol consumption) and self-perceived health were examined
      using logistic regression analyses. RESULTS: A stepwise gradient was found
      between education and self-perceived health for the total sample, men, and women.
      Compared to people with high education, people with low education had a 4.5 times
      higher chance of assessing their health as poor. Unemployed (odds ratio [OR],
      1.64; 95% confidence interval [CI], 1.29-2.10), inactive (OR, 2.82; 95% CI, 2.49
      3.19), and the most deprived respondents (OR, 1.17; 95% CI, 1.02-1.34) were more
      likely to report poor self-perceived health than employed persons and the most
      affluent group. After adjustment for demographic and health behavior variables,
      the magnitudes of all associations decreased but remained clearly and
      significantly graded. CONCLUSIONS: This study revealed inequalities in self
      perceived health by socioeconomic position, in particular educational and
      employment status. The reduction of such inequalities through wisely tailored
      interventions that benefit people's health should be a target of a national
      health policy in Serbia.

PMID- 22661141
TI  - Turkish school teachers' knowledge and attitudes toward HIV/AIDS.
AB  - AIM: To assess Turkish school teachers' knowledge, attitudes, and misconceptions
      of HIV/AIDS. METHODS: This cross-sectional descriptive study was conducted in
      Sivas, Middle Anatolian province of Turkey, from January to May 2009. We selected
      and interviewed 898 teachers using a simple systematic sampling method. RESULTS:
      All respondents heard about AIDS. Most knew that it could be transmitted by
      infected blood (98.0%) and sexual contact (93.4%) and some (33.2%) thought that
      it could be transmitted by mosquitoes. Although the majority of them strongly
      agreed or agreed with the statement that "people with AIDS should be helped,
      supported and treated" (98.0%), about 40% and 70% of them, respectively, agreed
      or strongly agreed with the statement that infected people should be quarantined.
      Young teachers with a higher level of knowledge about HIV/AIDS had more positive
      attitudes. CONCLUSION: This study provided basic information on school teachers'
      AIDS knowledge and attitudes and showed that various misconceptions of HIV
      transmission were a matter of concern. A considerable number of respondents with
      undesirable attitudes toward HIV/AIDS indicates the need for education of
      teachers on the subject.

PMID- 22661140
TI  - Job satisfaction of nurses and identifying factors of job satisfaction in
      Slovenian Hospitals.
AB  - AIM: To determine the level of job satisfaction of nursing professionals in
      Slovenian hospitals and factors influencing job satisfaction in nursing. METHODS:
      The study included 4 hospitals selected from the hospital list comprising 26
      hospitals in Slovenia. The employees of these hospitals represent 29.8% and 509
      employees included in the study represent 6% of all employees in nursing in
      Slovenian hospitals. One structured survey questionnaire was administered to the
      leaders and the other to employees, both consisting 154 items evaluated on a 5
      point Likert-type scale. We examined the correlation between independent
      variables (age, number of years of employment, behavior of leaders, personal
      characteristics of leaders, and managerial competencies of leaders) and the
      dependent variable (job satisfaction - satisfaction with the work, coworkers,
      management, pay, etc) by applying correlation analysis and multivariate
      regression analysis. In addition, factor analysis was used to establish
      characteristic components of the variables measured. RESULTS: We found a medium
      level of job satisfaction in both leaders (3.49+/-0.5) and employees (3.19+/
      0.6), however, there was a significant difference between their estimates
      (t=3.237; P=lt;0.001). Job satisfaction was explained by age (Plt;0.05;
      beta=0.091), years of employment (Plt;0.05; beta=0.193), personal characteristics
      of leaders (Plt;0.001; beta=0.158), and managerial competencies of leaders
      (Plt;0.000; beta=0.634) in 46% of cases. The factor analysis yielded four factors
      explaining 64% of the total job satisfaction variance. CONCLUSION: Satisfied
      employees play a crucial role in an organization's success, so health care
      organizations must be aware of the importance of employees' job satisfaction. It
      is recommended to monitor employees' job satisfaction levels on an annual basis.

PMID- 22661142
TI  - The perception and knowledge of cardiovascular risk factors among medical
      students.
AB  - AIM: To assess perceptions, knowledge, and awareness of cardiovascular disease
      (CVD) risk factors among medical students (freshmen and graduating students).
      METHODS: A descriptive cross-sectional survey based on an anonymous self
      administered questionnaire was conducted in 2008 on 443 medical students - 228
      freshmen on their enrollment day and 214 students on the day of their final exam
      at the University of Zagreb School of Medicine, Croatia. RESULTS: The perception
      and knowledge of some CVD risk factors, eg, dyslipidemia, arterial hypertension,
      and metabolic syndrome as well as of lipid-lowering therapy important for CVD
      prevention was significantly better among graduating students but was still not
      sufficient. Only 66% of graduating students reported that they would prescribe
      lipid-lowering therapy to high risk patients. Disappointingly, many graduating
      students were smoking (30.4%) and had low-awareness of obesity as an important
      CVD risk factor. CONCLUSION: These results suggest an urgent need to improve
      medical students' knowledge of obesity and low physical activity as important CVD
      risk factors and of the methods for increasing low high-density lipoprotein
      cholesterol and for smoking cessation. All this provides a rationale for
      modifying the university core curriculum to include more information concerning
      these issues.

PMID- 22661143
TI  - Bio-objects as "boundary crawlers:" the case of microRNAs.
AB  - microRNAs (miRNAs), short RNAs of 21-25 nucleotides, are implied in gene
      expression and regulation, in biological processes and in human pathologies
      including cancer. Since miRNAs of plant origin can survive digestion and cooking
      and enter in animal (including human) sera and tissues, their intervention in
      mammalian gene expression and regulation might be expected. Mouse experimental
      feeding, in fact, showed that a miRNA class (MIR168a) is involved in accumulation
      of the low-density lipoprotein (LDL), the major cholesterol-carrying lipoprotein
      of human plasma. Considering LDL's role in atherosclerosis, a negative influence
      of miRNAs from food origin on our health may be expected. Here we concentrate on
      the miRNAs' capability to cross inter-kingdom boundaries through the diet and
      acting as a "boundary crawler." The boundary between plant and human is presented
      under a new perspective, where a new intimate relationship between two genomes -
      mammalian and plant - belonging to quite different kingdoms is proposed. The
      food's role as molecule carrier in our health is also discussed. miRNAs, finally,
      are presented as an example of "bio-objects" with impact on both medical and
      cultural issues.

PMID- 22661144
TI  - Stem cell transplantation in neuroscience: the role of molecular imaging.

PMID- 22661145
TI  - Commentary to the article: asymptomatic lumbosacral lipomas--a natural history
      study, by Wykes V, Desai D, and Thompson DNP.

PMID- 22661146
TI  - Neuronal injury and cytogenesis after simple febrile seizures in the hippocampal
      dentate gyrus of juvenile rat.
AB  - PURPOSE: Although simple febrile seizures are frequently described as harmless,
      there is evidence which suggests that hippocampal damage may occur after simple
      febrile seizures. This study aimed to investigate possible neuronal damages as
      well as alterations in cytogenesis in the hippocampal dentate gyrus following
      simple febrile seizures. METHODS: Simple febrile seizure was modeled by
      hyperthermia-induced seizures in 22-day-old male rats. The brains were removed 2
      or 15 days after hyperthermia in all rats with (n=20) and without (n=10)
      occurrence of seizures as well as in control animals (n=10). The sections were
      stained with hematoxylin and eosin to estimate the surface numerical density of
      dark neurons. Ki-67 immunohistochemistry was performed to evaluate changes of
      cytogenesis following simple febrile seizures. RESULTS: Hyperthermia induced
      behavioral seizure activities in 67 % of the rats. The numerical densities of
      dark neurons as well as the mean Ki-67 index (the fraction of Ki-67-positive
      cells) were significantly increased in dentate gyrus after induction of seizures
      by hyperthermia compared to both controls and rats without seizure after
      hyperthermia. Both the seizure duration and intensity were correlated
      significantly with numerical densities of dark neurons (but not with Ki-67
      index). CONCLUSION: The data indicate that simple febrile seizures can cause
      neuronal damages and enhancement of cytogenesis in the hippocampal dentate gyrus,
      which were still visible for at least 2 weeks. These findings also suggest the
      correlation of febrile seizure intensity and duration with neuronal damage.

PMID- 22661147
TI  - Unusual presentation of Chiari I in toddlers: case reports and review of the
      literature.
AB  - Toddlers with Chiari malformations can present with common symptoms, such as
      cough or drooling, which are associated with respiratory illnesses, delaying a
      correct diagnosis. Presentation does vary with age, and therefore can be
      different in older children when compared to infants. We present two cases of
      unusual presentations in toddlers and review the literature with an emphasis on
      acute presentation of Chiari in different age groups in children.

PMID- 22661148
TI  - Personality and psychopathology in African unaccompanied refugee minors:
      repression, resilience and vulnerability.
AB  - Examining personality and psychopathological symptoms among unaccompanied refugee
      minors (URMs), we measured intra-individual dimensions (repression and correlates
      thereof) usually associated with resilience. Forty-one URMs completed the
      Weinberger Adjustment Inventory (WAI), assessing personality, and the Youth Self
      Report (YSR), describing current symptoms. URMs endorsed high levels of
      Repressive Defensiveness, Denial of Distress, and Restraint; unexpectedly, URMs
      reported high Distress and reduced Happiness (WAI, p's < 0.05). Although YSR
      symptoms were below clinical cut points, there were notable correlations between
      Distress and Attention Problems, Self-destructive, and Aggressive Behavior (all
      on the YSR), correcting for multiple comparisons (p's < 0.004). URMs exposed to
      non-normative stressors reported non-symptomatic outcomes, and high levels of
      personality dimensions correlating with resilience. However, URMs also endorsed
      high Distress and low Happiness, calling their resilience into question. Positive
      correlations between WAI Distress and YSR symptom subscales suggest that URMs
      harbor vulnerabilities of clinical and forensic significance.

PMID- 22661149
TI  - Dismissing children's perceptions of their emotional experience and parental
      care: preliminary evidence of positive bias.
AB  - The tendency to perceive caregivers in highly positive terms and to perceive the
      self as strong and problem-free are two facets of the positive bias
      characteristic of a dismissing attachment classification in adulthood. However,
      this link has not yet been examined in children. We evaluated the association
      between dismissing attachment and positive bias in school-aged children's reports
      of their own emotional experience and their parental care, hypothesizing that:
      (1) compared to secure children, dismissing children would underreport their
      subjective distress relative to physiological indicators of distress, and (2)
      dismissing children would report that their parents were warmer/more caring than
      would secure children. Ninety-seven children between the ages of 8 and 12
      completed the Child Attachment Interview, reports of maternal and paternal care,
      and a psychophysiological threat paradigm. Compared to secure children,
      dismissing children reported less distress than their startle responses during
      threat would suggest. In other words, dismissing children showed a greater
      divergence between subjective and physiological emotional response. Dismissing
      children rated their parents as warmer and more caring as compared to secure
      children's ratings. Results provide support for the association between
      dismissing attachment and inflated positivity on child-report measures of
      parental care and emotional experience. Implications of the study's findings for
      attachment theory are discussed.

PMID- 22661150
TI  - Trends in risk and protective factors for child bullying perpetration in the
      United States.
AB  - This study examines trends in prevalence and factors associated with bullying
      perpetration among children 10-17 years old, using the 2003 and 2007 National
      Survey of Children's Health. A parent-reported bullying measure and NSCH-designed
      questions were used to measure factors associated with bullying. The 2003 (n =
      48,639) and 2007 (n = 44,152) samples were 51 % male, with mean age of 13.5
      (standard deviation 2.3). 23 % of children bullied at least sometimes in 2003 and
      15 % bullied in 2007. Parental anger with their child, a child
      emotional/developmental/behavioral problem, and suboptimal maternal mental health
      were associated with higher bullying odds in 2003 and 2007, whereas parents
      talking with their child very/somewhat well, and meeting their child's friends
      were associated with lower odds. Between 2003 and 2007, parental anger with their
      child was associated with increasing bullying odds and parents' meeting their
      child's friends was associated with decreasing odds. Targeting these persistent
      factors may result in effective bullying-prevention interventions.

PMID- 22661153
TI  - Resuscitating competence in advanced life support.

PMID- 22661151
TI  - Working memory, attention, inhibition, and their relation to adaptive functioning
      and behavioral/emotional symptoms in school-aged children.
AB  - The present study investigated the development of executive functions (EFs) and
      their associations with performance and behavior at school in 8-12-year-old
      children. The EFs were measured by computer-based n-back, Continuous Performance
      and Go/Nogo tasks. School performance was evaluated by Teacher Report Form (TRF)
      and behavior by TRF and Child Behavior Checklist. The studied dimensions of EF
      were cognitive efficiency/speed, working memory/attention and inhibitory control.
      Strong age effects were found for these cognitive abilities (p values <0.01).
      Inhibitory control was associated with better adaptive functioning (learning,
      working hard and behaving well), academic performance and less psychiatric
      symptoms (p values <0.05), specially in 8-9-year-old children. In this youngest
      age group low inhibitory control was also associated with teacher-reported
      inattention (p = 0.042). Low inhibitory control was associated with teacher- and
      parent-reported internalizing symptoms (p < 0.01). These results suggest that
      maturational factors may underlie low adaptive functioning and psychiatric
      symptoms during early school years. Further studies are needed to evaluate the
      association between inhibition and emotional symptoms.

PMID- 22661154
TI  - Withdrawal of life-sustaining treatment: a case study.
AB  - Withdrawal of life support is an option for patients with prolonged mechanical
      ventilation when all attempts at weaning have failed and it is deemed futile to
      continue the therapy, when quality of life is unacceptable, or when it is
      perceived that the patient is suffering. The purpose of this article is to
      present the nursing aspects of managing an adult patient undergoing the
      withdrawal of mechanical ventilation as an end-of-life procedure. Withdrawal of
      mechanical ventilation is a complex and difficult process that requires
      meticulous planning and management. Conferences with the patient and the
      patient's family are critical to addressing emotional support and ensuring that
      everyone understands the process and is provided an opportunity to gather
      information. Clear communication with patients and their families can ensure that
      the process goes smoothly. Having an organized approach can ensure that patients
      experience a peaceful death and staff experience closure regarding the event.

PMID- 22661155
TI  - Tend and befriend in the intensive care unit.
AB  - Stress is a common phenomenon in the intensive care unit for both patients and
      nurses. Critical care nurses may experience many forms of stress, including
      physical, psychological, and moral stress or distress. The physiological stress
      response traditionally associated with the hypothalamic-pituitary-adrenal axis
      has been expanded to include a new model, called tend and befriend, that has been
      linked to females of different species, including humans. Studies have shown that
      stress also affects immune function. Although commonly associated with adverse
      outcomes, stress can lead to personal growth. The tend and befriend strategy is
      an intervention that was developed to help nurses increase their ability to grow
      from stressful situations, especially those related to moral distress.

PMID- 22661156
TI  - Engaging families to participate in care of older critical care patients.
AB  - Provision of optimal outcomes for older adults can be understood through the use
      of the American Association for Critical-Care Nurses Synergy Model. These
      outcomes can be enhanced if strategies are designed to improve the
      characteristics of patients and families as described in the Synergy Model. When
      older adults are admitted to critical care units, spouses, children, and friends
      are in a position to participate in care. This column examines the Synergy
      Model's patient characteristic of participation in care relative to involvement
      of the family and significant others of the older patient as a method of
      enhancing optimal outcomes.

PMID- 22661157
TI  - Contrast-induced nephropathy: nursing implications.
AB  - Contrast-induced nephropathy is a major adverse event that occurs during studies
      that require contrast medium. Almost 10% of all hospital-acquired instances of
      renal insufficiency are directly attributed to contrast material, with
      significantly higher mortality and morbidity than cases that do not involve
      contrast material. Contrast material causes an acceleration of the renal
      vasoconstrictive response, which results in a cascade of events that affect the
      vasoregulatory system. Multiple prophylactic measures must be instituted when
      considering a patient for a contrast study. Critical care nurses are pivotal in
      identifying patients' risk factors and potential nephrotoxic agents in order to
      avoid contrast-induced nephropathy. This article outlines the pathophysiology and
      definitions of normal kidney function, nephropathy, and chronic kidney disease.

PMID- 22661158
TI  - Teaching strategies to support evidence-based practice.
AB  - Evidence-based practice is an expected core competency of all health care
      clinicians regardless of discipline. Use of evidence-based practice means
      integrating the best research with clinical expertise and patient values to
      achieve optimal health outcomes. Evidence-based practice requires nurses to
      access and appraise evidence rapidly before integrating it into clinical
      practice. Role modeling and integrating the skills necessary to develop evidence
      based practice into clinical and nonclinical courses is an important part in
      developing positive attitudes toward evidence-based practice, an essential first
      step to using evidence to guide practice decisions. The step-by-step approach to
      evidence-based practice proposed by Melnyk and colleagues provides an excellent
      organizing framework for teaching strategies specifically designed to facilitate
      nurses' knowledge and skill development in evidence-based practice.

PMID- 22661159
TI  - Multidisciplinary simulation in pediatric critical care: the death of a child.
AB  - Health care providers are trained to care for the living. They may complete their
      education and enter the workforce without ever experiencing the death of a
      patient. Inexperience with the different roles of the multidisciplinary health
      care team is common. Moreover, the death of a child has a profound effect on
      parents and staff. In such situations, the expertise of the multidisciplinary
      team can make a difference. A multidisciplinary education project that uses high
      fidelity simulation based on pediatric death and dying was developed to provide
      an experience during which health care practitioners could practice communicating
      with families about the death of their child and dealing with different grief
      reactions.

PMID- 22661160
TI  - Measuring central venous pressure with a triple-lumen catheter.

PMID- 22661161
TI  - Pressure ulcers in the intensive care unit: new perspectives on an old problem.

PMID- 22661162
TI  - Prevention of aspiration.

PMID- 22661164
TI  - I am a critical care nurse.

PMID- 22661165
TI  - Residual neuromuscular blockade in critical care.
AB  - Neuromuscular blockade is a pharmacological adjunct for anesthesia and for
      surgical interventions. Neuromuscular blockers can facilitate ease of
      instrumentation and reduce complications associated with intubation. An
      undesirable sequela of these agents is residual neuromuscular blockade. Residual
      neuromuscular blockade is linked to aspiration, diminished response to hypoxia,
      and obstruction of the upper airway that may occur soon after extubation. If an
      operation is particularly complex or requires a long anesthesia time, residual
      neuromuscular blockade can contribute to longer stays in the intensive care unit
      and more hours of mechanical ventilation. Given the risks of this medication
      class, it is essential to have an understanding of the mechanism of action of,
      assessment of, and factors affecting blockade and to be able to identify factors
      that affect pharmacokinetics.

PMID- 22661166
TI  - Hyponatremia caused by polydipsia.
AB  - Hyponatremia (serum sodium <135 mEq/L) is the most common electrolyte disorder.
      The severity of symptoms is related to how rapidly the condition develops and the
      degree of cerebral edema that results from the low serum level of sodium.
      Hypertonic saline and the new vasopressin receptor antagonists are highly
      effective treatments for severe symptomatic hyponatremia, yet they can result in
      severe neurological complications if sodium levels are restored too quickly.
      Hyponatremia is classified as hypovolemic, euvolemic, and hypervolemic.
      Treatments include administration of high-risk medications and fluid restriction
      to restore fluid and electrolyte balance and relieve cerebral effects. Nursing
      care to ensure safe outcomes involves multidisciplinary collaboration, close
      monitoring of serum sodium levels and intake and output, and assessment for
      neurological changes.

PMID- 22661167
TI  - Expression of biologically active human interferon alpha 2b in the milk of
      transgenic mice.
AB  - Interferon alpha 2b (IFNalpha-2b) is an important immune regulator widely used in
      clinic, for the treatment of chronic hepatitis, hairy cell leukemia, chronic
      myelogenous leukemia and multiple myeloma, etc. The clinically used IFNalpha-2b
      is generally produced by E.Coli, which lacks the post-translational O
      glycosylation presents on naturally synthesized protein, and has a short serum
      half-life. In this study, a transgenic cassette pBCN-IFN-pA-CMV-EGFP was
      constructed, with a 5.2 kb beta-casein regulation fragment from Jersey cow and a
      6*His tagged human Interferon alpha 2b (hIFNalpha-2b) gene fragment. By using
      pronuclear microinjection technique, transgenic mice were generated and the
      expression of IFNalpha-2b in the milk was assayed. The hIFNalpha-2b was correctly
      translated in milk of transgenic mice according to Western blot analysis. The
      expression level of hIFNalpha-2b was varied among the transgenic mice, and the
      highest one was about 29.71 MUg/L. The recombinant protein exhibited biological
      activity in vitro by increasing the luminescence value and the MxA gene
      expression in established WISH cells, and the specific activity is approximately
      2.8 * 10(7 )IU/mg. The expression of recombinant hIFNalpha-2b in mammary glands
      of transgenic mice constitutes an important step towards low-cost and full
      biological activity production of this protein drug in mammary gland bioreactor.

PMID- 22661168
TI  - Current evidence for human yersiniosis in Ireland.
AB  - Yersiniosis associated with abdominal pain was commonly reported in Ireland in
      the 1980s. However, the Health Protection Surveillance Centre (HPSC) currently
      records only three to seven notified cases of yersiniosis per year. The most
      common cause of yersiniosis worldwide is Yersinia enterocolitica, and the leading
      source for this organism is consumption of pork-based food products. In contrast
      to the apparent current scarcity of yersiniosis cases in humans in Ireland,
      pathogenic Y. enterocolitica are detectable in a high percentages of pigs. To
      establish whether the small number of notifications of human disease was an
      underestimate due to lack of specific selective culture for Yersinia, we carried
      out a prospective culture study of faecal samples from outpatients with
      diarrhoea, with additional culture of throat swabs, appendix swabs and screening
      of human sewage. Pathogenic Yersinia strains were not isolated from 1,189 faeces
      samples, nor from 297 throat swabs, or 23 appendix swabs. This suggested that
      current low notification rates in Ireland are not due to the lack of specific
      Yersinia culture procedures. Molecular screening detected a wider variety of Y.
      enterocolitica-specific targets in pig slurry than in human sewage. A serological
      survey for antibodies against Yersinia YOP (Yersinia Outer Proteins) proteins in
      Irish blood donors found antibodies in 25 %, with an age-related trend to
      increased seropositivity, compatible with the hypothesis that yersiniosis may
      have been more prevalent in Ireland in the recent past.

PMID- 22661169
TI  - Catheter-related infections in pediatric patients with cancer.
AB  - Central venous catheters (CVCs) are essential in the management of pediatric
      patients receiving antineoplastic therapy or bone marrow transplants, and have
      significantly improved their quality of life, but CVC-related infectious
      complications are a major source of morbidity. It has been estimated that 14-51 %
      of the CVCs implanted in children with malignancies may be complicated by
      bacteremia, and that the incidence of infections is 1.4-1.9 episodes per 1,000
      CVC days. However, there are few recent data concerning the epidemiology of CVC
      related infections, the prevalence of antimicrobial resistance in their etiology,
      or the main factors associated with an increased risk of infection by type of
      catheter, patient age, the type of cancer, or the presence of neutropenia.
      Moreover, although various new strategies have been proposed in an attempt to
      reduce the risk of CVC-related infections, such as catheters impregnated with
      antiseptics/antibiotics, lock antibiotic prophylaxis, the use of ointments at the
      exit site, and antithrombotic prophylaxis, their real efficacy in children has
      not yet been demonstrated. The management of CVC-related infections remains
      difficult, mainly because of the number of still open questions (including the
      choice of optimal antimicrobial therapy because of the increasing isolation of
      multiresistant bacterial strains, treatment duration, whether catheters should be
      removed or not, the feasibility of guidewire exchange, and the usefulness of
      antibiotic lock therapy) and the lack of studies of children with cancer. Only
      well-designed, prospective clinical trials involving pediatric cancer patients
      can clarify optimal prevention and treatment strategies for CVC-related
      infections in this population.

PMID- 22661170
TI  - Hospital-related outbreaks due to rare fungal pathogens: a review of the
      literature from 1990 to June 2011.
AB  - Fungi can cause severe infections. Two or more nosocomial unusual fungal
      infections diagnosed in a short period should be assumed as an outbreak. The
      review's aim was to collect data to improve their management. The free online
      worldwide database for nosocomial outbreaks ( http://www.outbreak-database.com )
      and the PubMed/MEDLINE database were used to collect the English literature
      published from 1990 to June 2011. The more common Candida spp. and Aspergillus
      spp. infections were excluded. For each outbreak, the following data were
      reviewed: species, duration, source and site of infection, ward, risk factors,
      number of patients infected, treatment, related mortality, type of
      epidemiological study and time elapsed between index cases and second cases.
      Thirty-six reports were considered: yeasts caused the majority of the outbreaks
      (16 out of 36). The median values for the overall duration, number of infected
      people per outbreak and infection-related mortality were 5 months, 4 and 20 %,
      respectively. Eighteen cases were caused by contaminated substances and 13 cases
      were hypothesised as human-transmitted. Nosocomial outbreaks due to rare fungal
      pathogens involve few patients but have high related mortality. These results
      could be explained by the diagnostic delay, the inability of recognising the
      source of the infections and the challenges of the treatment. More efforts should
      be concentrated to implement the application of proper hygiene practices to avoid
      human-human transmission.

PMID- 22661171
TI  - Cancer control in the Asia Pacific region: current status and concerns.
AB  - Cancer is becoming an increasingly important health problem in the low- and
      middle-income countries in the Asia Pacific region, as well as in high-income
      countries because of ageing populations and changes in lifestyle associated with
      economic development and epidemiologic transition. This paper reviews the cancer
      burden and control in the Asia Pacific region (limited to East Asia, South
      Eastern Asia and Pacific Islands countries, territories and other areas), with
      relevant information primarily extracted from the GLOBOCAN 2008, Cancer Incidence
      in Five Continents series and WHO websites. Most low- and middle-income countries
      have a cancer control strategy and/or an action plan; however, coverage of cancer
      registration is still very low and does not meet the international standard in
      terms of quality. Therefore, only limited data were available for the recent
      global estimation of cancer burden. Large variations, in both cancer incidence
      and mortality, were observed in the populations in the different sub-regions of
      Asia. The most common cancer in males is lung cancer in the Eastern and South
      Eastern sub-regions, while prostate cancer comes close to lung cancer in the
      Pacific Island countries. In females, breast cancer is the most common in all
      three regions. The predominance of lung, stomach, colorectal, prostate, breast
      and cervical cancers makes cancer control more amenable in the Asia Pacific
      region. Up-to-date statistics on cancer occurrence and outcome are essential for
      the planning and evaluation of cancer control programmes. Priority can be given
      to population-based cancer registration, risk reduction, especially tobacco
      control, and primary health care based enhancement of health care systems to
      diagnose and manage cancer specifically in low- and middle-income countries.

PMID- 22661172
TI  - Preserving integrity, along with fertility.

PMID- 22661173
TI  - Zinc deficiency induces behavioral alterations in the tail suspension test in
      mice. Effect of antidepressants.
AB  - BACKGROUND: Recently, experimental zinc deficiency has been correlated with
      depression-like alterations in rodents. METHODS: In the first part of present
      study, the time course of zinc deficient diet induced alterations in the tail
      suspension test (TST) in mice was investigated. In the second part, the effect of
      imipramine and escitalopram in control and zinc-deprived for 3 weeks mice was
      examined in the TST. RESULTS: A4- and 10-week administration of a Zn-deficient
      diet enhanced the immobility time in the TST (by 20% and 57%, respectively). By
      contrast, a 2-week period of a zinc deficient diet effected the reduction (by
      24%) of the immobility time. Moreover, a 2- and 4-week (but not 10-week) of a Zn
      deficient diet resulted in the reduction of the body weight (by 37% and 18%,
      respectively). These results indicate the developing response to zinc deficiency
      induced by a zinc-deficient diet. The antidepressant-like effect (reduction in
      the immobility time) of both drugs was significantly reduced in zinc-deprived
      mice, which suggests treatment-resistance induced by zinc deprivation.
      CONCLUSION: Zinc deprivation induces "pro-depressive" behavior and alters
      antidepressant efficacy.

PMID- 22661174
TI  - Acute and repeated treatment with the 5-HT7 receptor antagonist SB 269970 induces
      functional desensitization of 5-HT7 receptors in rat hippocampus.
AB  - BACKGROUND: SB 269970, a 5-HT(7) receptor antagonist may produce a faster
      antidepressant-like effect in animal models, than do antidepressant drugs, e.g.,
      imipramine. The present work was aimed at examining the effect of single and
      repeated (14 days) administration of SB 269970 on the 5-HT(7) receptor in the
      hippocampus. METHODS: The reactivity of 5-HT(7) receptors was determined using 5
      carboxamidotryptamine (5-CT), which increased the bursting frequency of
      spontaneous epileptiform activity in hippocampal slices. Additionally, the
      effects of SB 269970 administration on the affinity and density of 5-HT(7)
      receptors were investigated using [(3)H]-SB 269970 and the influence of SB 269970
      and imipramine on mRNA expression levels of Galpha(s) and Galpha(12) mRNA were
      studied using RT-qPCR. RESULTS: Acute and repeated treatment with SB 269970 led
      to attenuation of the excitatory effects of activation of 5-HT(7) receptors.
      Neither single nor repeated administration of SB 269970 changed the mean affinity
      of 5-HT(7) receptors for [(3)H]-SB 269970. Repeated, but not single,
      administration of SB 269970 decreased the maximum density of [(3)H]-SB 269970
      binding sites. While administration of imipramine did not change the expression
      of mRNAs for Galpha(s) and Galpha(12) proteins after both single and repeated
      administration of SB 269970, a reduction in Galpha(s) and Galpha(12) mRNA
      expression levels was evident. CONCLUSIONS: These findings indicate that even
      single administration of SB269970 induces functional desensitization of the 5
      HT(7) receptor system, which precedes changes in the receptor density. This
      mechanism may be responsible for the rapid antidepressant-like effect of the 5
      HT(7) antagonist in animal models.

PMID- 22661175
TI  - Neonatal serotonin (5-HT) depletion does not affect spatial learning and memory
      in rats.
AB  - BACKGROUND: Extensive previous research has suggested a role for serotonin (5-HT)
      in learning and memory processes, both in healthy individuals and pathological
      disorders including depression, autism and schizophrenia, most of which have a
      developmental onset. Since 5-HT dysfunction in brain development may be involved
      in disease etiology, the present investigation assessed the effects of neonatal 5
      HT depletion on spatial learning and memory in the Morris water maze (MWM).
      METHODS: Three days old Sprague-Dawley rats were pretreated with desipramine (20
      mg/kg) followed by an intraventricular injection of the selective 5-HT neurotoxin
      5,7-dihydroxytryptamine (5,7-DHT, 70 MUg). Three months later rats were tested in
      the MWM. RESULTS: Despite a severe and permanent decrease (80-98%) in
      hippocampal, prefrontal and striatal 5-HT levels, treatment with 5,7-DHT caused
      no spatial learning and memory impairment. CONCLUSIONS: Limited involvement of
      chronic 5-HT depletion on learning and memory does not exclude the possibility
      that this neurotransmitter has an important neuromodulatory role in these
      functions. Future studies will be needed to identify the nature of the
      compensatory processes that are able to allow normal proficiency of spatial
      learning and memory in 5-HT-depleted rats.

PMID- 22661176
TI  - Flutamide treatment induces anxiolytic-like behavior in adult castrated rats.
AB  - BACKGROUND: It has previously been speculated that the androgen receptor
      antagonist flutamide produces behavioral effects that are not mediated by
      androgen receptors. These earlier studies were performed in intact rodents and
      thus, flutamide may have interfered with endogenous testosterone produced by the
      testes. The main objective of the present study was to examine whether flutamide
      induces anxiolytic-like behavior in castrated rats. METHODS: Male Wistar rats (8
      9 weeks old) were castrated and thereafter, in the same operation, the rats
      received silastic capsules subcutaneously (sc) that were filled with
      dihydrotestosterone (DHT) or were left empty. Three weeks later, rats were sc
      administered flutamide 50 mg/kg/day or vehicle for seven days. Four hours after
      the last injection, anxiolytic-like behavior was studied in a modified Vogel's
      drinking conflict model. In a separate experiment, shock threshold and drinking
      motivation were estimated. RESULTS: Flutamide induced anxiolytic-like behavior in
      castrated rats irrespective of administration of DHT. Treatment with DHT alone
      did not induce a significant behavioral effect. Shock threshold and drinking
      motivation were not affected by flutamide and/or DHT treatment. CONCLUSIONS: This
      study demonstrates that flutamide induces anxiolytic-like behavior in a modified
      Vogel's conflict model in castrated rats, which indicates that flutamide has
      anxiolytic-like properties that are not dependent on testes-produced
      testosterone.

PMID- 22661177
TI  - Antinociceptive and anti-inflammatory activities of a sulfated polysaccharide
      isolated from the green seaweed Caulerpa cupressoides.
AB  - BACKGROUND: Red and brown algae sulfated polysaccharides (SPs) have been widely
      investigated as antinociceptive and/or anti-inflammatory agents; however, no
      description of these biological properties concerning green algae SPs have been
      reported. Caulerpa curpressoides (Chlorophyta) presents three SPs fractions (Cc
      SP1, Cc-SP2, and Cc-SP3). Anticoagulant (in vitro) and anti- and pro-thrombotic
      (in vivo) effects of Cc-SP2 had been recently reported. We evaluated the effects
      of Cc-SP2 using models of nociception and acute inflammation in vivo. METHODS:
      Male Swiss mice received Cc-SP2 (iv) 30 min prior to receiving 0.6% acetic acid
      (10 ml/kg, ip), 1% formalin (20 MUl, sc) or were subjected to thermal stimuli (51
      +/- 1  degrees C). Cc-SP2 was injected sc to male Wistar rats in a peritonitis
      model or a paw edema model using carrageenan (ip or ipl, 500 MUg). To analyze the
      systemic effects, Cc-SP2 (27 mg/kg, sc) was administrated to both genders mice
      before waiting for 14 days. RESULTS: Cc-SP2 (3, 9 or 27 mg/kg) reduced (p < 0.05)
      the number of writhes induced by acetic acid by 57, 89.9 and 90.6%, respectively,
      the licking time in the first (9 or 27 mg/kg with 42.47 and 52.1%, respectively)
      and the second (3, 9 or 27 mg/kg with 68.95, 82.34 and 84.61%, respectively)
      phases. In the hot-plate test, the antinociceptive effect of Cc-SP2 (9 mg/kg) was
      primarily observed at 60 min (26.7 +/- 1.2 s), with its effect reversed by
      naloxone (8.6 +/- 1.3 s), suggesting the involvement of the opioid system. Cc-SP2
      (3, 9 or 27 mg/kg, sc, p < 0.05) showed anti-inflammatory effects by decreasing
      neutrophils migration by 64, 69 and 73%, respectively, and potently reduced the
      paw edema, especially at the second (0.16 +/- 0.02, 0.16 +/- 0.03 and 0.12 +/-
      0.05 ml) and third (0.16 +/- 0.03, 0.18 +/- 0.02 and 0.14 +/- 0.04 ml) hours,
      respectively. Cc-SP2 did not cause hepatic or renal alterations or affect body
      mass or the macroscopy of the organs examined (p > 0.05). Histopathological
      analyses of the liver and kidney showed that both organs were affected by Cc-SP2
      treatment, but these effects were considered reversible. CONCLUSION: The results
      indicate that the analgesic and anti-inflammatory effects of Cc-SP2 could be of
      biomedical applicability as a new, natural tool in pain and acute inflammatory
      conditions.

PMID- 22661178
TI  - Evaluation and comparison of antinociceptive activity of aspartame with sucrose.
AB  - BACKGROUND: Artificial sweeteners are low-calorie substances used to sweeten a
      wide variety of foods. At present they are used increasingly not only by
      diabetics, but also by the general public as a mean of controlling the weight.
      This study was carried out to evaluate and compare antinociceptive activity of
      the artificial sweeteners, aspartame and sucrose and to study the mechanisms
      involved in this analgesic activity. METHODS: Forty eight white albino Wistar
      rats were divided into two groups of 24 rats each. Group 1 received sucrose and
      group 2 received aspartame solution ad libitum for 14 days as their only source
      of liquid. On 14(th) day, both groups of rats were divided into 3 subgroups
      having 8 rats each. Group Ia and IIa served as control. Group Ib and IIb were
      given naloxone and Ic and IIc received ketanserin, the opioid and serotonergic
      receptor antagonists, respectively. RESULTS: Tail withdrawal latencies (tail
      flick analgesiometer) and paw licking/jumping latencies (Eddy's hot plate method)
      were increased significantly in both aspartame and sucrose group. The analgesia
      produced by aspartame was comparable with sucrose. The opioid receptor antagonist
      naloxone and the 5-HT(2A/2C) serotonergic receptor antagonist ketanserin partly
      reversed the antinociceptive effect of these sweeteners. CONCLUSIONS: Thus, the
      artificial sweetening agent aspartame showed antinociceptive activity like
      sucrose in rats. Reduction in antinociceptive activity of aspartame and sucrose
      by opioid and serotoninergic antagonists demonstrate the involvement of both
      opioid and serotonergic system.

PMID- 22661179
TI  - Antinociception by metoclopramide, ketamine and their combinations in mice.
AB  - BACKGROUND: Metoclopramide is a centrally acting antiemetic and ketamine is a
      general anesthetic used with sedatives, tranquilizers and analgesics.
      Metoclopramide has analgesic effects and its combination with ketamine causes
      sedation and hypnosis. The contribution of metoclopramide to the analgesic effect
      of ketamine is not known. The purpose of the present study was to explore the
      analgesic effects of metoclopramide and ketamine alone or in combination in mice.
      METHODS: The up-and-down method was used to determine the median effective
      analgesic dosages (ED(50)s) of metoclopramide and ketamine administered
      intraperitoneally (ip) either alone or concomitantly in male albino Swiss mice.
      Analgesia was measured by using a hot plate. The ED(50)s of both drugs were
      analyzed isobolographically to determine the type of interaction between them.
      The analgesic effect of metoclopramide-ketamine combination (62.3 and 4.3 mg/kg,
      ip) was also monitored by the hot plate and acetic acid writhing methods.
      RESULTS: The analgesic ED(50)s for metoclopramide and ketamine in mice were 30.15
      and 2.15 mg/kg, ip, respectively. Concomitant administration of the drugs reduced
      their ED(50)s to 10.17 and 0.68 mg/kg, ip, respectively. Isobolographic analysis
      of these ED(50)s for both drugs revealed synergistic analgesic effect. Further,
      the combination of the drugs was effective analgesic as seen by the hot plate
      test and by another analgesic test paradigm, the acetic acid-induced writhings in
      mice. CONCLUSIONS: The data suggest that the combination of metoclopramide and
      ketamine synergistically controls acute pain in mice. This combination could be
      used clinically for restraint and minor surgical interventions in mice.

PMID- 22661180
TI  - Influence of calcium channel blockers on anticonvulsant and antinociceptive
      activities of valproic acid in pentylenetetrazole-kindled mice.
AB  - BACKGROUND: Comorbidities of epilepsy comprise some pain disorders, including
      acute nociceptive pain, therefore, antiepileptic drugs can prove efficacy in the
      management of this kind of pain albeit with several adverse reactions. The
      current study aimed to evaluate the modulatory effects of calcium channel
      blockers on the anticonvulsant and antinociceptive effects of valproic acid (VPA)
      in pentylenetetrazole (PTZ)-kindled mice. METHODS: Kindled mice were treated with
      20 mg/kg (ip) of diltiazem, nifedipine, or verapamil, then VPA(200 mg/kg, ip) at
      30 min intervals before PTZ administration (35 mg/kg, ip). RESULTS: Our data
      demonstrated that the three calcium channel blockers afforded a protection
      against sub-convulsive doses of PTZ. Their protective effects were comparable to
      that exerted by the standard antiepileptic drug, VPA. The anticonvulsant activity
      of VPA was further enhanced by its combination with diltiazem. Also, PTZ-kindling
      reduced pain-threshold as evaluated by hot plate analgesimeter and acetic acid
      induced writhing test. Although the repeated administration of VPA significantly
      increased pain-threshold in kindled mice, it was not able to normalize it.
      Similar results were obtained with diltiazem and nifedipine. Interestingly,
      combination of diltiazem or nifedipine with VPA elicited the most profound
      antinociceptive effect in kindled mice. CONCLUSIONS: These results demonstrate
      for the first time the beneficial role of some calcium channel blockers in
      combination with VPA in the management of acute nociceptive pain.
      Therapeutically, this enhancing profile for calcium channel blockers fosters a
      safer and more effective drug-combination regimen than valproic acid alone.

PMID- 22661181
TI  - Effect of hydrochlorothiazide on the anticonvulsant action of antiepileptic drugs
      against maximal electroshock-induced seizures in mice.
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of
      hydrochlorothiazide (HCTZ), a thiazide-type diuretic and an antihypertensive
      drug, on the anticonvulsant activity of numerous antiepileptic drugs (AEDs:
      carbamazepine--CBZ, phenytoin--PHT, valproate--VPA, phenobarbital--PB,
      oxcarbazepine--OXC, lamotrigine--LTG and topiramate--TPM). METHODS: The effects
      of HCTZ and AEDs on convulsions were examined in the maximal electroshock seizure
      (MES) test in mice. Additionally, adverse effects of combined treatment with HCTZ
      and the AEDs in the passive avoidance task and chimney test were assessed. All
      drugs were injected intraperitoneally (ip) at single doses. RESULTS: The data
      obtained indicate that HCTZ (100 mg ip) enhanced the anticonvulsant action of
      CBZ, decreasing its ED(50) value from 11.9 to 7.7 mg/kg (p < 0.05), and had no
      impact on the antielectroshock activity of the other AEDs. The observed
      interaction between HCTZ and CBZ was not pharmacokinetic in nature as HCTZ did
      not alter free plasma (non-protein-bound) and total brain concentrations of CBZ.
      The combined treatment with HCTZ and the AEDs was free from side-effects on motor
      performance and long-term memory in mice. CONCLUSIONS: To the degree, the
      experimental data can be transferred to clinical conditions, the use of a single
      dose of HCTZ in patients receiving VPA, PHT, PB, OXC, LTG or TPM, seems neutral
      regarding their anticonvulsant potency. Acute HCTZ may positively influence the
      anticonvulsant action of CBZ in epileptic patients.

PMID- 22661182
TI  - Effects of different priming doses of fentanyl on fentanyl-induced cough: a
      double-blind, randomized, controlled study.
AB  - BACKGROUND: Fentanyl-induced cough is not an uncommon phenomenon during the
      induction of general anesthesia. A preliminary randomized controlled study was
      designed to observe the effects of different priming doses of fentanyl on
      fentanyl-induced cough during induction of anesthesia. METHODS: Four hundred
      patients were randomized into four groups (n = 100 for each). Group I received 5
      ml saline 0.9% 1 min before administration of fentanyl 2.5 MUg/kg; group II
      received pre-emptive fentanyl 0.5 MUg/kg 1 min before administration of fentanyl
      2 MUg/kg; group III received pre-emptive fentanyl 1 MUg/kg 1 min before
      administration of fentanyl 1.5 MUg/kg; and group IV received pre-emptive fentanyl
      1.5 MUg/kg 1 min before administration of fentanyl 1 MUg/kg. The severity of
      cough was graded as none (0), mild (1-2), moderate (3-4), or severe (5 or more
      episodes). We defined T1 and T2 as the 1 min periods after the first and second
      injections, respectively, and recorded the number of patients whose first cough
      happened in the T1 or T2 period. RESULTS: The incidences of fentanyl-induced
      cough were 68%, 5%, 40% and 64% in groups I, II, III and IV, respectively. The
      incidence of cough in group II was lower than those in groups III and IV in the
      T1 period. The incidences of cough in groups II, III and IV were lower than that
      in group I in the T2 period. CONCLUSIONS: In summary, a priming dose of fentanyl
      0.5 MUg/kg suppressed fentanyl-induced cough during induction of anesthesia in
      clinical practice. Fentanyl-induced cough was positively correlated with the dose
      of fentanyl.

PMID- 22661184
TI  - Significance of genetic polymorphism of CYP2D6 in the pathogenesis of systemic
      sclerosis.
AB  - BACKGROUND: Systemic sclerosis (SSc) belongs to the group of systemic diseases of
      the connective tissue, which are characterized by a chronic autoimmune
      inflammatory process. The studies on etiopathogenesis of autoimmune diseases
      focus on the impact the genetically conditioned impairment of xenobiotic
      metabolism may exert. The genetically polymorphic CYP2D6 is one of the most
      important phase I drug metabolizing enzymes. The knowledge of oxidation
      polymorphism in the course of SSc may be helpful in choosing more efficient and
      safer therapy, particularly in the case of a disease involving various organs and
      treated with drugs belonging to diverse therapeutic groups. The aim of the study
      was to evaluate the CYP2D6 polymorphism in the SSc patients and to investigate a
      possible correlation with disease susceptibility. METHODS: The study was carried
      out in 77 patients with SSc and 129 healthy volunteers. The CYP2D6 genotypes were
      analyzed by polymerase chain reaction fragment length polymorphism (PCR-RFLP)
      method. RESULTS: Risk of SSc development for particular genotype carriers
      expressed by the odds ratio (OR) was statistically significantly higher for
      subjects with CYP2D6*1/CYP2D6*4 (OR = 3.2; p = 0.001). A statistically
      significant correlation between the CYP2D6*4 allele prevalence and the risk for
      developing SSc was found (OR = 1.6; p = 0.029). CONCLUSIONS: The obtained results
      may suggest the influence of CYP2D6*4 gene mutated alleles on increased incidence
      of systemic sclerosis.

PMID- 22661183
TI  - Synthesis, anticonvulsant activity and 5-HT1A/5-HT7 receptors affinity of 1-[(4
      arylpiperazin-1-yl)-propyl]-succinimides.
AB  - BACKGROUND: Epilepsy is the most prevalent neurological disorder, affecting
      approximately 50 million people worldwide. Even though significant advances have
      been made in epilepsy research, convulsions in about 30% of epileptics are still
      inadequately controlled by standard drug therapy. For this reason, constant
      attempts are made to investigate new chemical agents and mechanisms through which
      epilepsy can be effectively controlled. Therefore, in the present studies, a
      series of sixteen new 1-[(4-arylpiperazin-1-yl)-propyl]-3-methyl-3-phenyl- and 3
      ethyl-3-methylpyrrolidine-2,5-dione derivatives as potential anticonvulsant
      agents was synthesized. METHODS: Anticonvulsant properties were evaluated in the
      maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and
      psychomotor seizure (6-Hz) tests after intraperitoneal injection in mice. The
      acute neurological toxicity was determined in the motor impairment rotorod
      screen. RESULTS: The compounds showed activity at a dose of 30 mg/kg (4, 8, 16)
      or 100 mg/kg (6, 9, 10, 12, 17, 18) in the MES model in mice. Four or them (8,
      10, 16, 17) were also evaluated after po administration in rats. In this series,
      the most active was 1-{3-[4-(3-chlorophenyl)-piperazin-1-yl]-propyl}-3-methyl-3
      phenyl-pyrrolidine-2,5-dione (8) with the ED(50) value of 28.2 mg/kg, TD(50)
      value of 268.5 mg/kg and protective index of 9.52 after po administration in
      rats. CONCLUSIONS: Taking into consideration the role of 5-HT(1A) and 5-HT(7)
      receptor subtypes in relation to the control of seizures as well as the fact that
      all compounds obtained belong to the class of long-chain arylpiperazines, their
      serotonin 5-HT(1A) and 5-HT(7) receptor affinity was determined. The most potent
      5-HT(1A) receptor ligands are 2-OCH(3) (11, 19) and 3-Cl (8, 16) derivatives with
      K(i) = 72, 14 nM, and 109, 44 nM, respectively. With respect to the 5-HT(7)
      receptors, the best K(i) values were obtained for derivatives 8 and 11 (K(i) = 76
      nM and 63 nM, respectively).

PMID- 22661185
TI  - C3435T polymorphism of the ABCB1/MDR1 gene encoding P-glycoprotein in patients
      with inflammatory bowel disease in a Polish population.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) belongs to the group of chronic
      diseases of the gastrointestinal tract, prevalence of which is increasing in the
      Polish population. The two main clinical types of IBD are ulcerative colitis (UC)
      and Crohn's disease (CD). The expression level of the ABCB1/MDR1 gene which
      encodes P-glycoprotein seems to be of great prognostic relevance while evaluating
      patients' susceptibility to UC or CD. One of the most significant ABCB1/MDR1 gene
      mutations is the C3435T polymorphism. A decreased expression of the ABCB1/MDR1
      gene and lower P-glycoprotein activity has been associated with the 3435T
      variant. The aim of the study was to evaluate the C3435T polymorphism in the IBD
      patients and to investigate a possible correlation with disease susceptibility.
      METHODS: The study was performed on 108 patients with IBD and on 137 healthy
      individuals. All the participants were of Caucasian origin and came from central
      Poland. The C3435T polymorphism was analyzed by using the PCR-RFLP method.
      RESULTS: Our results showed that ORs for IBD development (including UC and CD)
      were elevated in individuals both with the 3435CC genotype and the 3435C allele.
      The differences in genotype and allele frequencies were not significant.
      CONCLUSIONS: The C3435T polymorphism of the ABCB1/MDR1 gene is not a risk factor
      for IBD, including UC and CD, in the population coming from central Poland.

PMID- 22661186
TI  - Antiarrhythmic effect of prolonged morphine exposure is accompanied by altered
      myocardial adenylyl cyclase signaling in rats.
AB  - BACKGROUND: Morphine is often administered to patients for pain management, but
      it is also recommended to ameliorate some types of cardiovascular diseases.
      Nevertheless, there is a lack of information regarding the effect of prolonged
      morphine treatment on myocardial adenylyl cyclase (AC) signaling, which plays an
      important role in regulating heart function. METHOD: The present work has
      investigated the consequences of 10-day administration of high morphine doses (10
      mg/kg per day) to adult Wistar rats for functioning of the G-protein-mediated AC
      signaling system. RESULTS: Morphine treatment appreciably affected neither the
      number of myocardial beta-adrenoceptors nor the content of selected subunits of
      trimeric G-proteins (G(s)alpha, G(i/o)alpha, G(z)alpha, G(q/11)alpha and Gbeta)
      but the amount of the dominant myocardial AC isoform V/VI almost doubled. These
      alterations were accompanied by a marked AC supersensitization: the enzyme
      activity stimulated by manganese, fluoride, forskolin or isoproterenol was
      considerably increased (by about 50-100%). In contrast, the ability of opioid
      agonists to inhibit forskolin-stimulated AC activity was slightly but
      significantly decreased in both groups. Besides that, morphine markedly decreased
      the incidence of ischemic ventricular arrhythmias induced by coronary artery
      occlusion, but did not significantly influence infarct size and arrhythmias
      occurring during reperfusion. CONCLUSION: Overall, these results indicate that
      prolonged treatment of rats with high doses of morphine substantially alters the
      function of myocardial G-protein-regulated AC signaling. These alterations are
      accompanied by a reduced susceptibility to ischemia-induced ventricular
      arrhythmias.

PMID- 22661187
TI  - Effects of pantoprazole on dual antiplatelet therapy in stable angina pectoris
      patients after percutaneous coronary intervention.
AB  - BACKGROUND: Our aim was to prospectively assess the potential influence of
      pantoprazole therapy on the antiplatelet effects of acetylsalicylic acid (ASA)
      and clopidogrel (CLO) in stable angina pectoris (SAP) patients after percutaneous
      coronary intervention (PCI). METHODS: Forty-four patients with SAP (CCS I-III)
      and successful PCI with stent implantation were enrolled into the study. The
      patients were divided into group proton pump inhibitors (PPI): 23 patients with
      indications for PPI (F/M = 9/14; age = 64 +/- 9; standard therapy + 20 mg
      pantoprazole) and the control group (group C): 21 patients (F/M = 6/15; age = 64
      +/- 8; standard therapy). The platelet function analysis in whole blood based on
      impedance aggregometry (ASPI, COL, ADP, TRAP tests) using Multiplate--V2.02.11
      was performed 18-24 h after the PCI + CLO loading dose (600 mg) and 30 days after
      PCI. RESULTS: Both baseline patient characteristics and clinical outcomes were
      comparable between the study groups. There were no differences in the mean values
      of the platelets (PTL) tests measured at the 30(th) day after PCI between both
      groups (PPI vs. C: ASPI: 24.6 +/- 10.0 vs. 42.1 +/- 14.8 U, COL: 32.9 +/- 8.6 vs.
      34.0 +/- 7.7 U, ADP: 26.8 +/- 12.4 vs. 30.4 +/- 8.1 U, TRAP: 78.7 +/- 16.6 vs.
      78.1 +/- 22.6 U, p = ns). The mean delta values of the PTL tests (18-24 h post
      PCI/30 days post-PCI) were also comparable between the groups. The PTL
      aggregometry results were related to time (ADP, ASPI, TRAP vs. time, p = 0.001;
      COL vs. time, p = 0.03)--the baseline values of ADP, ASPI, COL and TRAP tests
      were smaller than those measured after the one-month observation. CONCLUSION:
      Pantoprazole treatment does not impair the efficacy of dual antiplatelet therapy
      in patients with SAP after PCI.

PMID- 22661188
TI  - Single bout of endurance exercise increases NNMT activity in the liver and MNA
      concentration in plasma; the role of IL-6.
AB  - BACKGROUND: Methylnicotinamide (MNA) displays vasoprotective activity, however,
      the regulation of the activity of nicotinamide-N-methyltransferase (NNMT), is
      largely unknown. We analyze a possible involvement of IL-6 in the activation of
      NNMT-MNA pathway during an endurance exercise. METHODS: FVB, C57Bl/6J IL6(+/+)
      and C57Bl/6J IL-6(-/-) mice were subjected to the single bout of endurance
      exercise consisting of 90 min of swimming. Thereafter, exercise-induced changes
      in NNMT activity in the liver as well as concomitant changes in the concentration
      of MNA and its further metabolites in plasma were analyzed. RESULTS: In two
      strains of mice (FVB and C57Bl/6J IL6(+/+)) 90 min of swimming resulted in
      approximately 2-3 folds increase in NNMT activity (from 0.14 +/- 0.03 to 0.421 +/
      0.02 pmol/min/mg, p < 0.05 and from 0.2 +/- 0.06 to 0.35 +/- 0.07 pmol/min/mg, p
      < 0.01, respectively) and concomitant increase in the plasma concentration of MNA
      (from 157 +/- 15.06 to 230 +/- 16.2 ng/ml, p < 0.01, and from 77.05 +/- 14.6
      ng/ml to 152.55 +/- 58.4 ng/ml; p < 0.01, respectively). However, in C57Bl/6J IL
      6(-/-) mice 90 min of swimming did not change liver NNMT activity (from 0.25 +/-
      0.07 to 0.23 +/- 0.06 pmol/min/mg), while MNA concentration in plasma rose
      approximately two-fold (from 65.3 +/- 30.9 ng/ml to 124.8 +/- 35.8 ng/ml; p <
      0.05). CONCLUSIONS: We demonstrated for the first time that NNMT - MNA pathway is
      activated by a single bout of endurance exercise. Interestingly, exercise-induced
      activation of NNMT in the liver involves IL-6, while the rise in MNA
      concentration in plasma was partially IL-6-independent. Taking into the
      consideration the pharmacological activity of MNA, IL-6-dependent and IL-6
      independent activation of NNMT, may contribute to the exercise capacity. The
      physiological role of NNMT in the exercise warrant further studies.

PMID- 22661189
TI  - Effectiveness of lipid-lowering therapy with statins for secondary prevention of
      atherosclerosis--guidelines vs. reality.
AB  - BACKGROUND: The aim of the study was to analyze the effectiveness of lipid
      lowering therapy and therapeutic decisions made by physicians for patients not
      achieving LDL targets. METHODS: 11,768 patients undergoing therapy with statins
      for secondary prevention of atherosclerosis participated in a two-visit survey.
      In subjects not achieving the LDL-target (< 100 mg/dl), further therapeutic
      decisions made by physicians were recorded. RESULTS: Initially the LDL-target was
      achieved by 7.8% of patients on simvastatin and by 18.0% on atorvastatin, of
      which 20.8% were treated with at least a 40 mg dose. The most common changes in
      therapy to improve effectiveness was substituting simvastatin for another statin
      (75.2%, usually atorvastatin), or increasing atorvastatin dosage (59.8%).
      Intensification of a low fat diet and weight reduction were more frequently
      recommended in treatment with atorvastatin than with simvastatin (59.8% vs.
      55.9%, p < 0.001). After enhanced therapy, the LDL-target was achieved by 27.8%
      on simvastatin and by 35.0% on atorvastatin (p < 0.001). In those with LDL levels
      remaining above the target, substitution of simvastatin with atorvastatin
      (49.9%), or the increase of atorvastatin dose (41.4%) was recommended. As
      previously, life-style counseling was more frequent in patients on atorvastatin
      (66.1% vs. 45.7% p < 0.001). CONCLUSIONS: 1. The use of low dose statins and
      noncompliance with behavioral modification guidelines are responsible for the low
      levels of effectiveness found with lipid-lowering therapies. 2. Physicians prefer
      substitution of less effective statins over the increase of dose in patients not
      achieving LDL targets. 3. Life-style changes are under-prescribed by physicians
      and under-implemented by their patients.

PMID- 22661190
TI  - Effects of thalidomide on the development of bone damage caused by prednisolone
      in rats.
AB  - BACKGROUND: The methods used in treatment of osteoporosis induced by
      glucocorticosteroids are not effective enough. There is a need for new drugs
      which could be useful in counteracting the influence of glucocorticosteroids on
      osseous tissue. The aim of the present study was to investigate the effects of
      thalidomide on the development of osteoporosis induced by glucocorticoid
      (prednisolone) in rats. METHODS: The experiments were carried out on 3-month-old
      male Wistar rats. The animals were divided into 4 groups: I--control rats; II-
      prednisolone (10 mg/kg po); III--prednisolone (10 mg/kg po) + thalidomide (15
      mg/kg po); IV--prednisolone (10 mg/kg po) + thalidomide (60 mg/kg po). The drugs
      were administered for 3 weeks. The body mass gain, bone mass in the tibia, femur
      and L-4 vertebra, histomorphometric parameters of the tibia (width of osteoid,
      diaphysis transverse growth, area of the transverse cross-sectional of the bone
      marrow cavity and the cortical bone) and the femur (width of trabeculae, width of
      epiphyseal cartilage, diaphysis transverse growth, area of the transverse cross
      sectional of the bone marrow cavity and the cortical bone) were studied. RESULTS:
      Prednisolone induced osteoporotic skeletal changes in mature male rats (decreases
      in the bone mass, the width of the periosteal and endosteal osteoid, the
      transverse cross-sectional area of the cortical bone, the width of trabeculae,
      and the diaphysis transverse growth were observed). Thalidomide administered at a
      dose of 15 mg/kg po inhibited the development of changes in macrometric and
      histomorphometric parameters induced by prednisolone in the skeletal system of
      rats. CONCLUSION: The results may constitute indirect evidence for possible
      clinical trials conducted in order to define the possibility to apply thalidomide
      in treatment of bone diseases in humans.

PMID- 22661191
TI  - Strontium ranelate treatment improves oxidative damage in osteoporotic rat model.
AB  - BACKGROUND: Osteoporosis is the most common skeletal disorder and is considered a
      risk of fracture. Most medication used for the treatment of osteoporosis is
      antiresorptive; however, strontium ranelate (Sr) therapy in postmenopausal women
      has shown a double effect on resorption and bone formation. In this study, the
      effect of Sr on status of the oxidative stress and antioxidant defence system was
      investigated. METHODS: Twenty-one adult albino female Wistar rats were used. The
      animals were randomly assigned into three groups, control (sham operated rats,
      received saline), OVX (ovariectomized rats), OVX + Sr (4 months later
      ovariectomy, strontium ranelate treatment was begun and continued for 120 days)
      each containing 7 animals. Strontium ranelate (500 mg/kg/day) and placebo
      (saline) were administered via oral gavage. At the end of the treatment, liver
      and kidney of rats were removed and malondialdehyde (MDA) level, superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities
      were determined by biochemical analysis methods. RESULTS: In liver, MDA levels
      were significantly higher in the OVX and OVX + Sr groups than the control group.
      GSH-Px activity decreased in OVX group and increased in OVX + Sr group compared
      with values of control group. CAT activity was increased in the OVX + Sr group
      when compared to control group. In kidney, MDA level was increased in OVX group.
      SOD activity was decreased in the OVX + Sr group. GSH-Px activity decreased in
      OVX group and increased in OVX + Sr group compared with control group. CAT
      activity increased in the OVX + Sr group when compared to control. CONCLUSION:
      According to our results, Sr has preventive effect on oxidative damage in
      ovariectomized rats.

PMID- 22661192
TI  - Restoration of immune system function is accelerated in immunocompromised mice by
      the B-cell-tropic isoxazole R-11.
AB  - BACKGROUND: Restoration of impaired immune response in immunocompromised patients
      is a crucial problem. In this study we evaluated the efficacy of isoxazole R-11
      in reconstitution of the immune response in immunosuppressed mice. METHODS: Mice
      were given a sublethal dose (250 mg/kg b.w.) of cyclophosphamide (CP). The
      cellular immune response to ovalbumin (OVA) and the humoral immune response to
      sheep erythrocytes (SRBC) were generated. R-11 was administered at repetitive,
      intraperitoneal doses (20 MUg/mouse) until determination of the immune responses:
      7 and 15 doses on alternate days for cellular and humoral immune response,
      respectively. For phenotypic studies R-11 was given per os, at a single dose of
      20 MUg/mouse. The ability of R-11 to affect interleukin- 6 (IL-6) production was
      determined in the whole human blood cell culture. RESULTS: R-11 increased the
      content of CD19+ cells in the spleens and lymph nodes with a concomitant decrease
      of CD3+ and CD4+ cells. The compound significantly accelerated restoration of
      both cellular and humoral immune responses, elevated the numbers of circulating
      leukocytes and splenocytes and normalized the blood cell picture. Supplementary
      experiments showed that R-11 was not toxic with regard to human peripheral blood
      mononuclear cells (PBMC) and that it upregulated IL-6 production in blood cell
      culture stimulated with lipopolysaccharide (LPS). CONCLUSIONS: We demonstrated
      that R-11 is likely a B-cell tropic agent which can restore both cellular and
      humoral immune responses in immunocompromised mice and may have a potential to be
      applied in therapy of immunocompromised patients.

PMID- 22661193
TI  - Apoptotic gene expression under influence of fludarabine and cladribine in
      chronic lymphocytic leukemia-microarray study.
AB  - BACKGROUND: A deep insight into gene expression profiling (GEP) is a key to
      understanding the background of disease. It can lead to identification of
      diagnostic and prognostic factors and then to a selection of the most appropriate
      therapy. The aim of this study was to evaluate differences in apoptotic gene
      expression in chronic lymphocytic leukemia (CLL) cells influenced by fludarabine
      (FA) or cladribine (2-CdA). METHODS: GEP was performed in cells obtained from 10
      untreated CLL patients and cultured in vitro with FA or 2-CdA. Ninety-three
      selected apoptotic genes were analyzed using 384 TaqMan(r) Low Density Arrays in
      pooled RNA. RESULTS: Relevant results were found in a set of 27 genes, however,
      the most striking differences between FA and 2-CdA were observed in the following
      5 genes: BAD, TNFRSF21, DAPK1, CARD 6 and CARD 9. CONCLUSION: We have found some
      differences in apoptotic gene expression between FAand 2-CdA. These findings give
      prominence to genes qualifying for further studies currently conducted in our
      Department.

PMID- 22661194
TI  - Pharmacokinetics and ocular disposition of paracetamol and paracetamol
      glucuronide in rabbits with diabetes mellitus induced by alloxan.
AB  - BACKGROUND: This study evaluates the pharmacokinetics (PK) and ocular disposition
      of paracetamol and paracetamol glucuronide in diabetic rabbits. METHODS: Thirty
      two New Zealand rabbits were divided into four groups: control group (I, n = 8),
      control group with diabetes (II, n = 8), rabbits with diabetes receiving
      paracetamol (III, n = 8), rabbits without diabetes receiving paracetamol (IV, n =
      8). To induce diabetes mellitus, alloxan was administrated intravenously (iv) in
      the dose of 90 mg/kg body weight (b.w.) to 16 rabbits (groups II and III). Eight
      weeks post induction of the diabetic state, paracetamol was administrated via the
      ear vein at a dose of 35 mg/kg b.w. to groups III and IV. Blood and aqueous
      (ocular fluid) samples were collected after drug administration. PK calculations
      were made based on non-compartmental analysis. RESULTS: Significant differences
      were observed in PK of paracetamol between the studied groups. Lower value of the
      area under the concentration--time curve and enhanced clearance of paracetamol
      were noted in the diabetic group. In the case of paracetamol glucuronide , the
      area under the concentration--time curve was also little lower; however, no
      changes in the elimination rate were observed. Simultaneously, diminished ocular
      disposition of paracetamol was obtained in the diabetic group, whereas no changes
      were noted according to the penetration of paracetamol glucuronide. CONCLUSIONS:
      The PK as well as ocular disposition of paracetamol may be altered in non-treated
      diabetes mellitus. The glucuronidation does not seem to be the process
      responsible for these changes.

PMID- 22661195
TI  - Preclinical pharmacokinetics of radiolabelled hyaluronan.
AB  - BACKGROUND: Hyaluronan (HYA) is a high molecular weight glucosaminoglycan with a
      great perspective for medical applications. Because HYA is widespread in the
      body, it is difficult to determine the fate of exogenously administered HYA.
      METHODS: In this study, HYAof different molecular weights (0.1-1 MDa) was
      labelled with (99m)Tc, and the distribution profiles were determined after
      administrating the HYA to rats. RESULTS: After the intravenous administration of
      (99m)Tc-HYA, a rapid decrease in the radioactivity of blood samples was observed,
      presumably because of (99m)Tc-HYA uptake by the liver; only minimal signs of
      liver radioactivity washout were detected. After the oral administration of
      (99m)Tc-HYA, no significant absorption to the central compartment was found. A
      preliminary study using (14)C-HYA exhibited a different distribution profile than
      (99m)Tc-HYA because of the different administered dose and the fate of the
      degradation products. Even with (14)C-HYA, only traces of radioactivity were
      absorbed after oral administration. CONCLUSION: This paper provides quantitative
      information regarding the distribution parameters of radiolabelled HYA in
      preclinical experiments.

PMID- 22661196
TI  - Effect of resveratrol on scopolamine-induced cognitive impairment in mice.
AB  - BACKGROUND: Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring
      compound found in grapes, wine, peanuts and cranberries. Recently, in vitro and
      cell culture studies have reported beneficial effects of resveratrol in the
      neurodegenerative process in Alzheimer's disease (AD). However, in vivo effect of
      resveratrol in models of learning and memory is not yet evaluated. The present
      study was performed to examine the effect of resveratrol on cognitive impairment
      induced by scopolamine, a muscarinic antagonist, in mice. METHODS: Scopolamine
      was administered in a dose of 1 mg/kg intraperitoneally (ip). Cognitive functions
      were assessed using transfer latency (TL) on elevated plus maze, step-down
      latency (SDL) on a passive avoidance apparatus and escape latency (EL) in Morris
      water maze test. RESULTS: Scopolamine produced significant prolongation of TL,
      reduction in SDL as well as EL showing cognitive impairment in mice. Pre
      treatment with resveratrol (10 mg/kg and 20 mg/kg, ip) for 21 days showed no
      difference in TL, SDL and EL. CONCLUSION: Resveratrol treatment does not reverse
      scopolamine-induced deficit in cognitive functions in mice.

PMID- 22661197
TI  - Differential effects of acute and repeated morphine treatment on kappa-opioid
      receptor mRNA levels in mesocorticolimbic system.
AB  - BACKGROUND: Morphine induces adaptive changes in gene expression throughout the
      reward circuitry of the brain. Here, we investigated the acute and chronic
      effects of morphine on mRNA levels of kappa-opioid receptor in the rat
      mesocorticolimbic system. METHODS: Three groups of rats received ip injection of
      saline, acute morphine (8.0 mg/kg) and repeated morphine (8.0 mg/kg, once daily
      for 5 consecutive days) and the kappa-receptor mRNA expression was examined using
      real-time quantitative PCR method. RESULTS: We found that kappa-receptor mRNA in
      medial prefrontal cortex (mPFC) increased after acute and repeated morphine
      treatment. However, the mRNA levels in nucleus accumbens (NAc) and ventral
      tegmental area (VTA) were upregulated after acute morphine treatment and returned
      to basal levels after repeated morphine treatment. CONCLUSIONS: These results
      suggest that morphine dependence was associated with regionally specific changes
      in mRNA levels of kappa-opioid receptor in mesocorticolimbic system.

PMID- 22661198
TI  - Serotonin 2A receptor gene (HTR2A) polymorphism in alcohol-dependent patients.
AB  - BACKGROUND: The serotonergic (5-HT) dysfunction has been frequently described in
      subjects with alcohol dependence (AD). In the present study, a potential
      relationship between T102C polymorphism in the 5-HT receptor subtype 2Agene
      (HTR2A) and alcohol dependence was examined. METHODS: Genotypes were analyzed in
      150 AD patients diagnosed with DSM-IV criteria and in 80 healthy controls.
      RESULTS: The genetic analysis showed that the frequency of 102C allele and C102C
      genotype in AD subjects was significantly higher than in controls. Moreover, AD
      patients homozygous for C allele had significantly lower age at onset of alcohol
      problems than subjects having at least one T allele. CONCLUSION: The results
      suggest a potential role of the T102C HTR2A polymorphism in development of
      alcohol dependence.

PMID- 22661199
TI  - Interleukin-13-induced activation of signal transducer and activator of
      transcription 6 is mediated by an activation of Janus kinase 1 in cultured human
      bronchial smooth muscle cells.
AB  - BACKGROUND: The current study was carried out to identify the JAK molecule(s)
      that is involved in the IL-13-induced activation of STAT6 in cultured human
      bronchial smooth muscle cells (hBSMCs). METHODS: Cultured hBSMCs were stimulated
      with IL-13 in the absence and presence of JAK inhibitor-I (a nonspecific JAKs
      inhibitor), tyrphostin-AG490 (a specific JAK2 inhibitor), WHI-P131 (a specific
      JAK3 inhibitor), or tyrphostin-AG9 (a specific Tyk2 inhibitor), and levels of
      phosphorylated STAT6 were measured by immunoblot analyses. RESULTS: The IL-13
      induced phosphorylation of STAT6 was abolished by JAK inhibitor-I, whereas the
      other inhibitors had no significant effect. CONCLUSION: These findings indicate
      that the STAT6 phosphorylation/activation induced by IL-13 is mediated by an
      activation of JAK1 in cultured hBSMCs.

PMID- 22661200
TI  - Automation in clinical biochemistry: core, peripheral, STAT, and specialist
      laboratories in Australia.
AB  - Pathology has developed substantially since the 1990s with the introduction of
      total laboratory automation (TLA), in response to workloads and the need to
      improve quality. TLA has enhanced core laboratories, which evolved from
      discipline-based laboratories. Work practices have changed, with central
      reception now loading samples onto the Inlet module of the TLA. It is important
      to continually appraise technology. This study looked at the impact of technology
      using a self-administered survey to seniors in clinical biochemistry in NATA
      GX/GY-classified laboratories in Australia. The responses were yes, no, or not
      applicable and are expressed as percentages of responses. Some of the questions
      sourced for descriptive answers. Eighty-one laboratories responded, and the
      locations were 63%, 33%, and 4% in capital cities, regional cities, and country
      towns, respectively. Forty-two percent were public and 58% private. Clinical
      biochemistry was in all core laboratories of various sizes, and most performed up
      to 20 tests per sample. Thirty percent of the 121 surveyed laboratories had plans
      to install an automated line. Fifty-eight percent had hematology and biochemistry
      instrumentations in their peripheral laboratory, and 16% had a STAT laboratory on
      the same site as the core laboratory. There were varied instruments in specialist
      laboratories, and analyzers with embedded computers were in all laboratories.
      Medium and large laboratories had workstations with integrated instruments, and
      some large laboratories had TLA. Technology evolution and rising demand for
      pathology services make it imperative for laboratories to embrace such changes
      and reorganize the laboratories to take into account point-of-care testing and
      the efficiencies of core laboratories and TLA.

PMID- 22661201
TI  - Hookworm infestation in south India--are we moving away from microscope?

PMID- 22661202
TI  - A decade's experience in lumbar spine surgery in Belgium: sickness fund
      beneficiaries, 2000-2009.
AB  - PURPOSE: The purpose is to study rates, trends, geographic variations and outcome
      of lumbar spine surgery in the Belgian population during the last decade.
      METHODS: This is a retrospective cohort study using administrative data of the
      largest Belgian sickness fund from January 1, 2000 through December 31, 2009.
      Cases included lumbar laminectomy, combined discectomy and fusion, posterior
      interarticular fusion, anterior lumbar interbody fusion (ALIF), posterior lumbar
      interbody fusion (PLIF) and standard discectomy. The main outcome measures were
      age- and sex-adjusted rates of lumbar spine surgery, 1-year mortality, 1-year
      iterative surgery, no return to work (RTW) rate 1 year after surgery and length
      of hospital stay. Multivariate logistic regression analysis was used to determine
      the association between age, sex, geographic region, type of surgery, year of
      intervention and duration of pre-operative sick leave on outcome. RESULTS: Spine
      surgery rates rose 44 % from 2001 through 2009 and data for 2009 showed twofold
      variations in spine surgery rates among 10 Belgian provinces. Reported 1-year
      mortality varied from 0.6 to 2.5 % among surgical procedures performed in 2008.
      The overall 5-year reoperation rate was 12 %. RTW rates 1 year after standard
      discectomy, ALIF, PLIF and combined discectomy and fusion for the follow-up
      sample of 2008 were 14.4, 22.7, 26.1 and 30.6 %, respectively. The median length
      of hospital stay significantly decreased throughout the decade. Type of surgery
      and geographic region were significantly related to patient outcomes.
      CONCLUSIONS: Regional variations highlight professional uncertainty and
      controversy. The study results point to the need for peer comparisons and surgeon
      feedback.

PMID- 22661203
TI  - New systemic therapy options for advanced sarcomas.
AB  - The outcome of patients with advanced soft tissue sarcomas (STS) has not improved
      much during the last decade. Apart from non-pleomorphic rhabdomyosarcoma,
      adjuvant chemotherapy has no standard role in high risk STS. In metastatic
      disease little progress has been made, but during recent years much effort has
      been put into the development of better clinical study protocols, with
      stratification of patients to at least the most common histological subtypes,
      preventing the dilution of potential treatment efficacy when measuring results
      over the total heterogeneous group of STS. The outcome of patients with advanced
      STS is however not only dependent on the introduction of new drugs, but also on
      the availability of dedicated sarcoma centers in which multidisciplinary teams
      with the input of all experts from different disciplines, such as pathology,
      radiology, nuclear medicine, surgery, orthopedics radiotherapy and medical
      oncology is present. Long delay, wrong histological diagnoses, under- and
      overtreatment are not in the favor of these patients, neither with regard to
      outcome, nor with respect to short- and long-term toxicity. Disappointedly,
      centralization is not a routine part of daily care of STS patients and their care
      givers. Patient advocacy groups are more and more aware of the relevance of
      treatment in centers of expertise and are active in guiding the patients to these
      hospitals. At the same time the sarcoma centers should be pro-active in putting
      patients into clinical trials, also for rare indications within the STS group, as
      only in this way a better outcome for this group of patients can be reached.

PMID- 22661204
TI  - The utility of injury narratives for prioritising future prevention activities in
      small and medium enterprises in rural Vietnam.
AB  - OBJECTIVES: Injuries are a leading cause of work-related disability and death in
      rapidly developing countries such as Vietnam. The authors' objective was to
      demonstrate the utility of detailed injury narratives, derived from a household
      survey, in providing information on the determinants of work-related injuries to
      inform potential intervention targets. METHODS: In a cross-sectional survey
      administered to 2615 households of a rapidly developing community of Vietnam
      where many workers engage in both agriculture and industrial work, the authors
      collected information about self-reported work-related injuries, annual hours
      worked in each industry and narrative text describing the circumstances of each
      injury. The authors used a customised coding taxonomy to describe injury
      scenarios. RESULTS: Several intervention themes emerged, including the
      implementation of machine guarding, the use of cut resistant gloves and safety
      glasses which would benefit the small- and medium-sized enterprises. Calculation
      of incidence rates using full-time equivalents, stratified by work group,
      provided some unexpected observations of the risks of working in agriculture;
      workers who work in agriculture in addition to another industry are at an
      increased risk of fatigue or overexertion and other consequences of working too
      hard in their agricultural activities. CONCLUSIONS: A lack of aggregate injury
      statistics makes it difficult for the owners of small- and medium-sized
      enterprises to recognise a priori the most effective safety interventions. This
      analysis of detailed injury narratives with an appropriate taxonomic basis offers
      the ability to focus on the level of cause, activity and source and may inform
      the choice of various potential interventions at the workplace or enterprise
      level.

PMID- 22661205
TI  - Injury risk and severity in a sample of Maryland residents with serious mental
      illness.
AB  - OBJECTIVE: Adults with serious mental illness experience premature mortality and
      heightened risk for medical disease, but little is known about the burden of
      injuries in this population. The objective of this study was to describe injury
      incidence among persons with serious mental illness. METHODS: We conducted a
      retrospective cohort study of 6234 Maryl and Medicaid recipients with serious
      mental illness from 1994-2001. Injuries were classified using the Barell Matrix.
      Relative risks were calculated to compare injury rates among the study cohort
      with injury rates in the United States population. Cox proportional hazards
      modeling with time dependent covariates was used to assess factors related to
      risk of injury and injury-related death. RESULTS: Forty-three percent of the
      Maryland Medicaid cohort had any injury diagnosis. Of the 7298 injuries incurred,
      the most common categories were systemic injuries due to poisoning (10.4%), open
      wounds to the head/face (8.9%), and superficial injuries, fractures, and sprains
      of the extremities (8.6%, 8.5%, and 8.4%, respectively). Injury incidence was 80%
      higher and risk for fatal injury was more than four and a half times higher among
      the cohort with serious mental illness compared to the general population.
      Alcohol and drug abuse were associated with both risk of injury and risk of
      injury-related death with hazard ratios of 1.87 and 4.76 at the p<0.05
      significance level, respectively. CONCLUSIONS: The superficial, minor nature of
      the majority of injuries is consistent with acts of minor victimization and
      violence or falls. High risk of fatal and non-fatal injury among this group
      indicates need for increased injury prevention efforts targeting persons with
      serious mental illness and their caregivers.

PMID- 22661206
TI  - Role of vitamin B12 on methylmalonyl-CoA mutase activity.
AB  - Vitamin B(12) is an organometallic compound with important metabolic derivatives
      that act as cofactors of certain enzymes, which have been grouped into three
      subfamilies depending on their cofactors. Among them, methylmalonyl-CoA mutase
      (MCM) has been extensively studied. This enzyme catalyzes the reversible
      isomerization of L-methylmalonyl-CoA to succinyl-CoA using adenosylcobalamin
      (AdoCbl) as a cofactor participating in the generation of radicals that allow
      isomerization of the substrate. The crystal structure of MCM determined in
      Propionibacterium freudenreichii var. shermanii has helped to elucidate the role
      of this cofactor AdoCbl in the reaction to specify the mechanism by which
      radicals are generated from the coenzyme and to clarify the interactions between
      the enzyme, coenzyme, and substrate. The existence of human methylmalonic
      acidemia (MMA) due to the presence of mutations in MCM shows the importance of
      its role in metabolism. The recent crystallization of the human MCM has shown
      that despite being similar to the bacterial protein, there are significant
      differences in the structural organization of the two proteins. Recent studies
      have identified the involvement of an accessory protein called MMAA, which
      interacts with MCM to prevent MCM's inactivation or acts as a chaperone to
      promote regeneration of inactivated enzyme. The interdisciplinary studies using
      this protein as a model in different organisms have helped to elucidate the
      mechanism of action of this isomerase, the impact of mutations at a functional
      level and their repercussion in the development and progression of MMA in humans.
      It is still necessary to study the mechanisms involved in more detail using new
      methods.

PMID- 22661207
TI  - Population structure and linkage disequilibrium in elite barley breeding
      germplasm from the United States.
AB  - Cultivated barley is known to have a complex population structure and extensive
      linkage disequilibrium (LD). To conduct robust association mapping (AM) studies
      of economically important traits in US barley breeding germplasm, population
      structure and LD decay were examined in a complete panel of US barley breeding
      germplasm (3840 lines) genotyped with 3072 single nucleotide polymorphisms
      (SNPs). Nine subpopulations (sp1-sp9) were identified by the program STRUCTURE
      and subsequently confirmed by principle component analysis (PCA). Out of the nine
      subpopulations, seven were very similar to the respective subpopulations
      identified by Hamblin et al. (2010) which were based on half of the germplasm and
      half of the SNP markers, but two subpopulations were found to be new. One
      subpopulation was dominated by six-rowed spring lines from Utah State University
      (UT) and the other was composed of six-rowed spring lines from multiple breeding
      programs (USDA-ARS Aberdeen (AB), Busch Agricultural Resources Inc. (BA), UT, and
      Washington State University (WA)). LD was found to decay across a range from 4.0
      to 19.8 cM. This result indicates that the germplasm genotyped with 3072 SNPs
      would be robust for mapping and possibly identifying the causal polymorphisms
      contributing to disease resistance and perhaps other traits.

PMID- 22661208
TI  - Genomic organization and sequence dynamics of the AvrPiz-t locus in Magnaporthe
      oryzae.
AB  - Plants utilize multiple layers of defense mechanisms to fight against the
      invasion of diverse pathogens. The R gene mediates resistance, in most cases,
      dependent on the co-existence of its cognate pathogen-derived avirulence (Avr)
      gene. The rice blast R gene Piz-t corresponds in gene-for-gene fashion to the
      Magnaporthe oryzae Avr gene AvrPiz-t. In this study, we determined and compared
      the genomic sequences surrounding the AvrPiz-t gene in both avirulent and
      virulent isolates, designating as AvrPiz-t-ZB15 and avrPiz-t-70-15 regions,
      respectively. The sequence of the AvrPiz-t-ZB15 region is 120966 bp whereas
      avrPiz-t-70-15 is 146292 bp in length. The extreme sequence similarity and good
      synteny in gene order and content along with the absence of two predicted genes
      in the avrPiz-t-70-15 region were observed in the predicted protein-coding
      regions in the AvrPiz-t locus. Nevertheless, frequent presence/absence and highly
      dynamic organization of transposable elements (TEs) were identified, representing
      the major variation of the AvrPiz-t locus between different isolates. Moreover,
      TEs constitute 27.3% and 43.2% of the genomic contents of the AvrPiz-t-ZB15 and
      avrPiz-t-70-15 regions, respectively, indicating that TEs contribute largely to
      the organization and evolution of AvrPiz-t locus. The findings of this study
      suggest that M. oryzae could benefit in an evolutionary sense from the presence
      of active TEs in genes conferring avirulence and provide an ability to rapidly
      change and thus to overcome host R genes.

PMID- 22661209
TI  - Identification of a heat shock cognate protein 70 gene in Chinese soft-shell
      turtle (Pelodiscus sinensis) and its expression profiles under thermal stress.
AB  - The heat shock cognate protein 70 (Hsc70) is a member of a 70-kDa heat shock
      protein (HSP70) family that functions as molecular chaperones. In this study, a
      novel Hsc70 gene from Chinese soft-shelled turtle (Pelodiscus sinensis) (tHsc70)
      was identified. The tHsc70 full-length complementary DNA (cDNA) is 2272 bp long
      with a 1941-bp open reading frame (ORF) encoding 646 amino acids. Three
      characteristic signature regions of the HSP70 family, two major domains of an
      adenosine triphosphate (ATP)/guanosine triphosphate (GTP) binding domain (ABD),
      and a substrate-binding domain (SBD) were present in the predicted tHsc70 amino
      acid sequence. The tHsc70 gene was expressed in Escherichia coli BL21 and the
      expression product reacted with the anti-Hsc70 mouse monoclonal antibody by
      Western blotting. Homology analysis revealed that tHsc70 shared identity from
      53.9% to 87.7% at the nucleotide level, and 49.1% to 99.5% at the amino acid
      level with the known Hsc70s. Phylogenetic analysis showed that tHsc70 was
      clustered together with the Hsc70 gene of another reptile species (Alligator
      mississippiensis). The tHsc70 was expressed in the liver, lung, heart, and
      skeletal muscle. The expression patterns of tHsc70 messenger RNA (mRNA) differed
      among different tissues under different durations of heat stress at 40  degrees
      C. Adaptation at 25  degrees C for 1 h after heat stress was also different among
      tissues and length of heat stress. Irrespective of different profiles of
      expression under heat stress, tHsc70 may play roles in protecting turtles from
      thermal stress.

PMID- 22661210
TI  - In vitro inhibition of pigmentation and fiber development in colored cotton.
AB  - Colored cotton has naturally pigmented fibers. The mechanism of pigmentation in
      cotton fiber is not well documented. This experiment was conducted to study the
      effects of respiratory chain inhibitors, i.e., rotenone and thiourea, on
      pigmentation and fiber development in colored cotton. After 1 d post-anthesis,
      ovaries were harvested and developing ovules were cultured on the liquid medium
      containing different concentrations of rotenone and thiourea for 30 d. The
      results demonstrate that both respiratory inhibitors reduced fiber length and
      ovule development under ovule culture conditions, and the inhibition efficiency
      of rotenone was much higher than that of thiourea. Rotenone and thiourea also
      showed significant effects on fiber pigment (color) development in colored
      cotton. In green cotton fiber, rotenone advanced fiber pigment development by 7 d
      at 200 MUmol/L, while thiourea inhibited fiber pigmentation at all treatment
      levels (400, 600, 800, 1000, and 2000 MUmol/L). Both respiratory inhibitors,
      however, had no significant effects on pigmentation of brown cotton fibers. The
      activities of cytochrome c oxidase (COX) and polyphenol oxidase (PPO) decreased
      significantly with increasing levels of both respiratory inhibitors. It is
      suggested that both respiratory inhibitors have important roles in deciphering
      the mechanism of pigmentation and fiber development in colored cotton.

PMID- 22661211
TI  - Caffeic acid product from the highly copper-tolerant plant Elsholtzia splendens
      post-phytoremediation: its extraction, purification, and identification.
AB  - In the current study, caffeic acid was an important metabolite in the highly
      copper-tolerant plant Elsholtzia splendens. Preparation and purification of
      caffeic acid were performed on the dried biomass of the plants by means of
      sonication/ethanol extraction, followed by purification using a macroporous resin
      (D101 type) column and silica gel chromatography. The faint-yellow caffeic acid
      product was yielded with a purity of 98.46%, and it was chemically identified
      from spectra of Fourier transform infrared spectroscopy (FTIR), proton nuclear
      magnetic resonance ((1)H NMR)/carbon nuclear magnetic resonance ((13)C NMR), and
      electrospray ionization mass spectrometry (ESI-MS). Caffeic acid is a possible
      product from the post-harvest processing of Elsholtzia splendens biomass.

PMID- 22661212
TI  - Cadmium accumulation in different pakchoi cultivars and screening for pollution
      safe cultivars.
AB  - The selection and breeding of pollution-safe cultivars (PSCs) is a practicable
      and cost-effective approach to minimize the influx of heavy metal to the human
      food chain. In this study, both pot-culture and field experiments were conducted
      to identify and screen out cadmium pollution-safe cultivars (Cd-PSCs) from 50
      pakchoi (Brassica rapa L. ssp. chinensis) cultivars for food safety. When treated
      with 1.0 or 2.5 mg/kg Cd, most of the pakchoi cultivars (>70%) showed greater or
      similar shoot biomass when compared with the control. This result indicates that
      pakchoi has a considerable tolerance to soil Cd stress. Cd concentrations in the
      shoot varied significantly (P<0.05) between cultivars: in two Cd treatments (1.0
      and 2.5 mg/kg), the average values were 0.074 and 0.175 mg/kg fresh weight (FW),
      respectively. Cd concentrations in the shoots of 14 pakchoi cultivars were lower
      than 0.05 mg/kg FW. In pot-culture experiments, both enrichment factors (EFs) and
      translocation factors (TFs) of six pakchoi cultivars were lower than 1.0. The
      field studies further confirmed that the Hangzhouyoudonger, Aijiaoheiye 333, and
      Zaoshenghuajing cultivars are Cd-PSCs, and are therefore suitable for growth in
      low Cd-contaminated soils (<=1.2 mg/kg) without any risk to food safety.

PMID- 22661213
TI  - Electrocatalytic response of poly(cobalt tetraaminophthalocyanine)/multi-walled
      carbon nanotubes-Nafion modified electrode toward sulfadiazine in urine.
AB  - A highly sensitive amperometric sulfadiazine sensor fabricated by electrochemical
      deposition of poly(cobalt tetraaminophthalocyanine) (poly(Co(II)TAPc)) on the
      surface of a multi-walled carbon nanotubes-Nafion (MWCNTs-Nafion) modified
      electrode is described. This electrode showed a very attractive performance by
      combining the advantages of Co(II)TAPc, MWCNTs, and Nafion. Compared with the
      bare glassy carbon electrode (GCE) and the MWCNTs-Nafion modified electrode, the
      electrocatalytic activity of poly(Co(II)TAPc)-coated MWCNTs-Nafion GCE generated
      greatly improved electrochemical detections toward sulfadiazine including low
      oxidation potential, high current responses, and good anti-fouling performance.
      The oxidation peak currents of sulfadiazine obtained on the new modified
      electrode increased linearly while increasing the concentration of sulfadiazine
      from 0.5 to 43.5 MUmol/L with the detection limit of 0.17 MUmol/L.

PMID- 22661214
TI  - Is integrative medicine the next new frontier in medicine?
AB  - Complementary and alternative medicine (CAM) methods are increasingly being used
      by patients in the Western world to treat autoimmune or allergic diseases.
      Patients use these methodologies of their own accord, frequently against the
      advice of their physicians. Integrative medicine hopes to merge the benefits of
      both conventional Western medicine and CAM. More and more research is being
      conducted to decipher the secrets behind the thousands of years of experience
      that CAM offers. Are these treatments effective, and are they safe? Or do they
      act simply by the "placebo effect." This unique issue attempts to bring
      integrative medicine to greater awareness among Western physicians and
      practitioners.

PMID- 22661215
TI  - Considerations for use of acupuncture as supplemental therapy for patients with
      allergic asthma.
AB  - This study examines the clinical and immunomodulatory effects of acupuncture in
      the treatment of patients with allergic asthma. The acupuncture points GV14,
      BL12, and BL13 were selected based on the theory of traditional Chinese medicine
      in treating asthma. Manual acupuncture was performed once every other day (three
      times per week) for 5 weeks. The needles were twisted approximately 360 degrees 
      evenly at the rate of 60 times/min for 20 s, manipulated every 10 min and
      withdrawn after 30 min. Concentrations of sIgA and total IgA in secretions were
      determined by the combination of sucrose density gradient ultracentrifugation and
      RIA. Levels of cortisol in the plasma were measured by RIA. Total IgE in the sera
      was examined by ELISA. Flow cytometry was used to detect the numbers of CD3+,
      CD4+, CD8+, and IL-2R + T lymphocytes in the peripheral blood. The absolute and
      differential numbers of eosinophils in peripheral blood were counted with eosin
      staining. The total efficacy of the acupuncture treatment in patients with
      allergic asthma at the end of one course of treatment was 85 %. After treatment,
      the concentrations of sIgA and total IgA in the saliva (P<0.01, P<0.02) and nasal
      secretions (P<0.02, P<0.02) were significantly decreased in patients with
      allergic asthma. The levels of total IgE in sera (P<0.001), the counts of IL-2R +
      T lymphocytes (P<0.001), and the absolute and differential numbers of eosinophils
      (P<0.01, P<0.01) in the peripheral blood were also significantly decreased. The
      numbers of CD3+, CD4+, and CD8+ T lymphocytes in the peripheral blood were
      significantly increased in the allergic asthmatics treated by acupuncture
      (P<0.001, P<0.01, and P<0.001, respectively). The concentration of cortisol in
      the plasma of asthmatic patients did not change significantly after the
      acupuncture treatment (P>0.05). Acupuncture has regulatory effects on mucosal and
      cellular immunity in patients with allergic asthma and may be an adjunctive
      therapy for allergic asthma.

PMID- 22661216
TI  - Induction of a broad spectrum of inflammation-related genes by Coxsackievirus B3
      requires Interleukin-1 signaling.
AB  - Coxsackievirus B3 (CVB3) is a major cause of acute and chronic forms of
      myocarditis. Previously, direct viral injury and post-infectious autoimmune
      response were suspected as main pathogenetic mechanisms. However, induction of
      pro-inflammatory cytokines may be crucial for pathogenesis in spite of host
      protein shut off caused by CVB3 replication. We investigated the global
      expression profile of pro-inflammatory genes induced by acute and persistent
      (carrier state) CVB3 infection in human fibroblast cell cultures with DNA
      microarrays, quantitative RT-PCR and ELISA. Rapid induction of a typical spectrum
      of about 30 inflammation-related genes (e.g., PTGS2, CCL2, IL-1beta, IL-6, IL-8,
      CSF2, MMP-1, MMP-3, and MMP-15) suggested an essential, autocrine role of IL-1.
      This hypothesis was confirmed by over-expression of IL-1RI, which resulted in a
      cytokine response upon CVB3 infection in HEK 293 cells otherwise refractory to
      CVB3-caused gene expression. Blocking IL-1 receptor type I (IL-1RI)-signaling
      during CVB3 infection with an IL-1 receptor antagonist (IL-1ra) as well as
      knockdown of IL-1RI using siRNA abrogated cytokine response in human fibroblasts.
      Both IL-1alpha and IL-1beta are relevant for the induction of inflammation
      related genes during CVB3 infection as shown by neutralization experiments.
      Paracrine effects of IL-1 on the subset of non-infected cells in carrier state
      infected fibroblast cultures enhanced induction of inflammation-related genes.
      CONCLUSIONS: A broad spectrum of inflammatory cytokines was induced by CVB3
      replication via a pathway that requires IL-1 signaling. Our results suggest that
      IL-1ra may be used as a therapeutic agent to limit inflammation and tissue
      destruction in myocarditis.

PMID- 22661217
TI  - Infection of neutrophil granulocytes with Leishmania major activates ERK 1/2 and
      modulates multiple apoptotic pathways to inhibit apoptosis.
AB  - Neutrophil granulocytes provide the first line of defense against bacterial,
      fungal, and parasitic infections. They phagocytose and kill many invading
      pathogens. Certain pathogenic microorganisms such as the intracellular protozoan
      parasite Leishmania major (L. major) can survive inside neutrophils. Mature
      neutrophils have a very short life span due to spontaneous apoptosis. Previously,
      we have reported that infections with L. major are able to delay spontaneous
      apoptosis. In the present study, we addressed the underlying mechanisms of
      regulation of both extrinsic and intrinsic apoptosis. We show that interaction
      with L. major transiently activates ERK1/2 phosphorylation. Pharmacological
      inhibition of ERK1/2 phosphorylation reversed the apoptosis delay. Moreover,
      infection leads to the enhanced and sustainable expression of the anti-apoptotic
      proteins Bcl-2 and Bfl-1, respectively. As downstream events, the release of
      cytochrome c from mitochondria and processing of caspase-6 were inhibited. We
      also confirm that infection with L. major results in reduced FAS expression on
      the surface of neutrophils. The presented data indicate that infection with L.
      major affects both intrinsic as well as extrinsic pathways of neutrophil
      apoptosis. Enhanced life span of host neutrophils enables the parasite to survive
      within neutrophils.

PMID- 22661218
TI  - Syndromic craniosynostosis, fibroblast growth factor receptor 2 (FGFR2)
      mutations, and sacrococcygeal eversion presenting as human tails.
AB  - INTRODUCTION: There have been 23 previously published cases of patients with
      syndromic craniosynostosis and human tails. In many of these, the tail was
      composed of prominent coccygeal and sacral vertebrae, curved in a retroverted
      instead of in the normal anterograde fashion. This has been termed sacrococcygeal
      eversion. In those cases in which genetic testing results are reported, there
      were fibroblast growth factor receptor 2 (FGFR2) mutations. METHODS: We present
      three patients with Pfeiffer syndrome and sacrococcygeal eversion. Two had
      genetic testing and both had FGFR2 mutations, one of them a novel mutation in
      patients with syndromic craniosynostosis and sacrococcygeal eversion. We also
      briefly review the literature on craniosynostosis and human tails. RESULTS: All
      but one reported patient has had either Pfeiffer, Crouzon, or Beare-Stevenson
      syndrome. Most patients, including ours, have had severe manifestations of their
      syndrome. Although the pathogenesis of sacrococcygeal eversion is unknown, a
      similarly posteriorly curved tail bud develops in normal human embryos during the
      second month of gestation. CONCLUSIONS: Perhaps increased FGFR2 activation during
      this embryonic period leads to abnormal differentiation or regression of the tail
      bud and, in turn, sacrococcygeal eversion, in certain patients with severe
      syndromic craniosynostosis.

PMID- 22661219
TI  - The evolution of cerebellar tonsillar herniation after cranial vault remodeling
      surgery.
AB  - PURPOSE: We sought to examine the pre- and postoperative changes of cerebellar
      tonsillar herniation by MR imaging in asymptomatic pediatric patients with
      nonsyndromic, single-suture craniosynostosis (N-SSSC), who underwent cranial
      vault remodeling surgery without suboccipital decompression. We required
      cerebellar tonsillar herniation through foramen magnum >=3 mm for Chiari type I
      malformation (CMI). We hypothesized that the increase of intracranial volume by
      cranial vault remodeling would correct the asymptomatic CMI. METHODS: We
      identified 9 patients among 121 N-SSSC children undergoing craniofacial surgery
      from January 2004 to October 2010 with CMI. However, two of them were excluded
      from the study due to missing postoperative MR images. In the final study
      population, six were males, five were scaphocephalic, while two were diagnosed
      with coronal synostosis. RESULTS: In four of the cases, the CMI was decreased in
      postoperative MR imaging varying from 6 to 12 mm. In three cases, the herniation
      remained stable. The median change of cerebellar tonsillar herniation was -6.5
      mm. CONCLUSIONS: We conclude that asymptomatic patients with existing CMI may
      benefit from cranial vault remodeling surgery alone increasing the intracranial
      volume.

PMID- 22661220
TI  - Evaluation of obstructive sleep apnea in pediatric patients with facio
      craniostenosis: a brief communication.
AB  - PURPOSE: This study aimed to evaluate our experience in treating cranio-maxillo
      mandibular malformations with hypoplasia of the upper and middle third of the
      face. We wished to determine a new diagnostic path involving a new clinical
      questionnaire for obstructive sleep apnea (OSA) evaluation, which we have
      developed by merging existing tests, literature findings, and our clinical
      experience to obtain a high level of information with minimal cost. This
      questionnaire is an improvement of the other anamnestic tests in the literature.
      METHODS: The study was carried out on 17 pediatric patients affected by syndromic
      craniofacial malformations and treated with surgical advancement of the middle
      third of the face, associated with or without upper third advancement, through
      osteodistraction. We used the obstructive airway child test (OACT) for clinical
      evaluation. The OACT is an OSA assessment test based on questions proposed to the
      patient's relatives. All patients underwent polysomnography for instrumental
      assessment of OSA. These patients were also required to have a computed
      tomography scan for surgical planning. At the start of the treatment, 11 patients
      had severe OSA, 4 patients had moderate OSA, and 2 patients had slight OSA.
      RESULTS: At the end of the treatment, 6 patients had slight OSA and 11 patients
      had no OSA; these data were confirmed with OACT and polysomnography. CONCLUSIONS:
      Based on our results, we suggest the following flowchart: OACT for OSA clinical
      evaluation; CT scan for evaluation of the volume of the rhinoropharyngeal air
      column, anatomical obstruction detection, and surgical planning; and
      polysomnography for diagnostic confirmation.

PMID- 22661221
TI  - Intrahost emergent dynamics of oseltamivir-resistant virus of pandemic influenza
      A (H1N1) 2009 in a fatally immunocompromised patient.
AB  - The oseltamivir-resistant pandemic influenza virus A (2009 H1N1) with H275Y
      mutation in neuraminidase (NA) has been sporadically reported, and its wide
      spread remains a potential threat. Here we detected the uneven distribution of
      H275Y mutant virus in a patient who received a 21-day long-term administration of
      oseltamivir. Intrahost variation of the virus showed that the H275Y mutant virus
      was the predominant population in both nasopharynx and right lung, whereas the
      oseltamivir-sensitive virus comprised half the population in the left lung. By
      constructing minimum spanning trees, it is proposed that the H275Y mutant might
      be generated primarily in the nasopharynx, then spread to the right and left
      lungs.

PMID- 22661222
TI  - P2X7 receptor activation mediates organic cation uptake into human myeloid
      leukaemic KG-1 cells.
AB  - The P2X7 purinergic receptor is an ATP-gated cation channel with an emerging role
      in neoplasia. In this study we demonstrate that the human KG-1 cell line, a model
      of acute myelogenous leukaemia, expresses functional P2X7. RT-PCR and
      immunochemical techniques demonstrated the presence of P2X7 mRNA and protein
      respectively in KG-l cells, as well as in positive control multiple myeloma RPMI
      8226 cells. Flow cytometric measurements demonstrated that ATP induced
      ethidium(+) uptake into KG-l cells suspended in sucrose medium (EC(50) of ~ 3
      MUM), but not into cells in NaCl medium. In contrast, ATP induced ethidium(+)
      uptake into RPMI 8226 cells suspended in either sucrose or NaCl medium (EC(50) of
      ~ 3 or ~ 99 MUM, respectively), as well as into RPMI 8226 cells in KCl medium
      (EC(50) of ~ 18 MUM). BzATP and to a lesser extent ATPgammaS and alphabeta
      methylene ATP, but not ADP or UTP, also induced ethidium(+) uptake into KG-1
      cells. ATP-induced ethidium(+) uptake was completely impaired by the P2X7
      antagonists, AZ10606120 and A-438079. ATP-induced ethidium(+) uptake was also
      impaired by probenecid but not by carbenoxolone, both pannexin-1 antagonists. ATP
      induced YO-PRO-1(2+) and propidium(2+) uptake into KG-1 cells. Finally,
      sequencing of full-length P2X7 cDNA identified several single nucleotide
      polymorphisms (SNPs) in KG-1 cells including H155Y, A348T, T357S and Q460R. RPMI
      8226 cells contained A348T, A433V and H521Q SNPs. In conclusion, the KG-1 cell
      line expresses functional P2X7. This cell line may help elucidate the signalling
      pathways involved in P2X7-induced survival and invasiveness of myeloid leukaemic
      cells.

PMID- 22661224
TI  - R-group template CoMFA combines benefits of "ad hoc" and topomer alignments using
      3D-QSAR for lead optimization.
AB  - Template CoMFA methodologies extend topomer CoMFA by allowing user-designated
      templates, for example the experimental receptor-bound conformation of a
      prototypical ligand, to help determine the alignment of training and test set
      structures for 3D-QSAR. The algorithms that generate its new structural modality,
      template-constrained topomers, are described. Template CoMFA's resolution of
      certain topomer CoMFA concerns, by providing user control of topological
      consistency and structural acceptability, is demonstrated for sixteen 3D-QSAR
      training sets, in particular the Selwood dataset.

PMID- 22661223
TI  - Dividing and conquering: controlling advanced melanoma by targeting oncogene
      defined subsets.
AB  - For decades, therapy for advanced melanoma has lagged behind most of the cancer
      field owing to its intrinsic resistance to conventional cytotoxic chemotherapy
      and limited impact of cytokine-based immunotherapy. The opportunity to develop
      molecularly targeted therapy emerged with the discovery of activating mutations
      in BRAF, a component of the long studied MAP kinase pathway. These mutations are
      found in approximately 50 % of patients with regionally advanced or metastatic
      melanoma and appear to be one of the initiating steps in the development of
      primary melanoma. Additional oncogenic events, particularly those that affect
      tumor suppressor genes, are essential for development of invasive and metastatic
      melanoma. Nonetheless, mutated BRAF retains its central contribution to melanoma
      pathophysiology even in advanced stage disease as manifested by the remarkable
      antitumor effects and alteration the natural history of metastatic melanoma of
      selective BRAF inhibitors. After initial response, resistance commonly emerges
      within a few months' time and the field has focused on delineating molecular
      mechanisms of resistance toward the goal of improving upon the early therapeutic
      effects of single agent BRAF inhibition. Combination regimens are currently
      undergoing clinical investigation. NRAS and CKIT mutant melanoma represent the
      next oncogene defined melanoma subsets for which initial targeted therapy
      approaches are being explored, with early evidence suggesting progress with MEK
      and CKIT inhibitors, respectively. A considerable subset of patients have
      melanomas that are not defined by the presence of BRAF, NRAS, or CKIT mutations
      and, thus, the elucidation of the entire melanoma genome is being pursued with
      the hope of identifying additional therapeutic targets.

PMID- 22661225
TI  - Telomere end processing: unexpected complexity at the end game.
AB  - Most human cells lack telomerase, the enzyme that elongates telomeres. The
      resulting telomere erosion eventually limits cell proliferation and tissue
      renewal, thereby impacting age-dependent pathologies. In this issue of Genes &
      Development, a technical tour-de-force by Chow and colleagues (pp. 1167-1178)
      reveals a highly choreographed sequence of events that processes newly replicated
      chromosome ends into mature telomeres. This sheds new light on an
      underappreciated contribution to telomere dynamics that may be as important as
      telomerase in dictating the correlation between life span and telomere length.

PMID- 22661226
TI  - Phosphorylation puts the pRb tumor suppressor into shape.
AB  - In this issue of Genes & Development, Burke and colleagues (pp. 1156-1166)
      describe how the structure of retinoblastoma protein (pRb) is altered by
      phosphorylation at T373 or S608. These modifications cause specific
      conformational changes and alter pRb's interaction with E2F via two distinct
      mechanisms. The structures suggest that the panel of phosphorylation sites
      represents a versatile set of tools that are used to sculpt pRb in precise, but
      very different, ways.

PMID- 22661228
TI  - Early and late steps in telomere overhang processing in normal human cells: the
      position of the final RNA primer drives telomere shortening.
AB  - Telomere overhangs are essential for telomere end protection and telomerase
      extension, but how telomere overhangs are generated is unknown. Leading daughter
      strands synthesized by conventional semiconservation DNA replication are
      initially blunt, while lagging daughter strands are shorter by at least the size
      of the final RNA primer, which is thought to be located at extreme chromosome
      ends. We developed a variety of new approaches to define the steps in the
      processing of these overhangs. We show that the final lagging RNA primer is not
      terminal but is randomly positioned ~70-100 nucleotides from the ends and is not
      removed for more than an hour. This identifies an important intrinsic step in
      replicative aging. Telomeric termini are processed in two distinct phases. During
      the early phase, which occupies 1-2 h following replication of the duplex
      telomeric DNA, several steps occur on both leading and lagging daughters. Leading
      telomere processing remains incomplete until late S/G2, when the C-terminal
      nucleotide is specified-referred to as the late phase. These observations suggest
      the presence of previously unsuspected complexes and signaling events required
      for the replication of the ends of human chromosomes.

PMID- 22661229
TI  - RNF4, a SUMO-targeted ubiquitin E3 ligase, promotes DNA double-strand break
      repair.
AB  - Protein ubiquitylation and sumoylation play key roles in regulating cellular
      responses to DNA double-strand breaks (DSBs). Here, we show that human RNF4, a
      small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, is recruited
      to DSBs in a manner requiring its SUMO interaction motifs, the SUMO E3 ligases
      PIAS1 and PIAS4, and various DSB-responsive proteins. Furthermore, we reveal that
      RNF4 depletion impairs ubiquitin adduct formation at DSB sites and causes
      persistent histone H2AX phosphorylation (gammaH2AX) associated with defective DSB
      repair, hypersensitivity toward DSB-inducing agents, and delayed recovery from
      radiation-induced cell cycle arrest. We establish that RNF4 regulates turnover of
      the DSB-responsive factors MDC1 and replication protein A (RPA) at DNA damage
      sites and that RNF4-depleted cells fail to effectively replace RPA by the
      homologous recombination factors BRCA2 and RAD51 on resected DNA. Consistent with
      previous data showing that RNF4 targets proteins to the proteasome, we show that
      the proteasome component PSMD4 is recruited to DNA damage sites in a manner
      requiring its ubiquitin-interacting domains, RNF4 and RNF8. Finally, we establish
      that PSMD4 binds MDC1 and RPA1 in a DNA damage-induced, RNF4-dependent manner and
      that PSMD4 depletion cause MDC1 and gammaH2AX persistence in irradiated cells.
      RNF4 thus operates as a DSB response factor at the crossroads between the SUMO
      and ubiquitin systems.

PMID- 22661230
TI  - SUMO-targeted ubiquitin E3 ligase RNF4 is required for the response of human
      cells to DNA damage.
AB  - Here we demonstrate that RNF4, a highly conserved small ubiquitin-like modifier
      (SUMO)-targeted ubiquitin E3 ligase, plays a critical role in the response of
      mammalian cells to DNA damage. Human cells in which RNF4 expression was ablated
      by siRNA or chicken DT40 cells with a homozygous deletion of the RNF4 gene
      displayed increased sensitivity to DNA-damaging agents. Recruitment of RNF4 to
      double-strand breaks required its RING and SUMO interaction motif (SIM) domains
      and DNA damage factors such as NBS1, mediator of DNA damage checkpoint 1 (MDC1),
      RNF8, 53BP1, and BRCA1. In the absence of RNF4, these factors were still
      recruited to sites of DNA damage, but 53BP1, RNF8, and RNF168 displayed delayed
      clearance from such foci. SILAC-based proteomics of SUMO substrates revealed that
      MDC1 was SUMO-modified in response to ionizing radiation. As a consequence of
      SUMO modification, MDC1 recruited RNF4, which mediated ubiquitylation at the DNA
      damage site. Failure to recruit RNF4 resulted in defective loading of replication
      protein A (RPA) and Rad51 onto ssDNA. This appeared to be a consequence of
      reduced recruitment of the CtIP nuclease, resulting in inefficient end resection.
      Thus, RNF4 is a novel DNA damage-responsive protein that plays a role in
      homologous recombination and integrates SUMO modification and ubiquitin signaling
      in the cellular response to genotoxic stress.

PMID- 22661227
TI  - Melanoma: from mutations to medicine.
AB  - Melanoma is often considered one of the most aggressive and treatment-resistant
      human cancers. It is a disease that, due to the presence of melanin pigment, was
      accurately diagnosed earlier than most other malignancies and that has been
      subjected to countless therapeutic strategies. Aside from early surgical
      resection, no therapeutic modality has been found to afford a high likelihood of
      curative outcome. However, discoveries reported in recent years have revealed a
      near avalanche of breakthroughs in the melanoma field-breakthroughs that span
      fundamental understanding of the molecular basis of the disease all the way to
      new therapeutic strategies that produce unquestionable clinical benefit. These
      discoveries have been born from the successful fruits of numerous researchers
      working in many-sometimes-related, although also distinct-biomedical disciplines.
      Discoveries of frequent mutations involving BRAF(V600E), developmental and
      oncogenic roles for the microphthalmia-associated transcription factor (MITF)
      pathway, clinical efficacy of BRAF-targeted small molecules, and emerging
      mechanisms underlying resistance to targeted therapeutics represent just a sample
      of the findings that have created a striking inflection in the quest for
      clinically meaningful progress in the melanoma field.

PMID- 22661231
TI  - Coordinated regulation of neuronal mRNA steady-state levels through
      developmentally controlled intron retention.
AB  - Differentiated cells acquire unique structural and functional traits through
      coordinated expression of lineage-specific genes. An extensive battery of genes
      encoding components of the synaptic transmission machinery and specialized
      cytoskeletal proteins is activated during neurogenesis, but the underlying
      regulation is not well understood. Here we show that genes encoding critical
      presynaptic proteins are transcribed at a detectable level in both neurons and
      nonneuronal cells. However, in nonneuronal cells, the splicing of 3'-terminal
      introns within these genes is repressed by the polypyrimidine tract-binding
      protein (Ptbp1). This inhibits the export of incompletely spliced mRNAs to the
      cytoplasm and triggers their nuclear degradation. Clearance of these intron
      containing transcripts occurs independently of the nonsense-mediated decay (NMD)
      pathway but requires components of the nuclear RNA surveillance machinery,
      including the nuclear pore-associated protein Tpr and the exosome complex. When
      Ptbp1 expression decreases during neuronal differentiation, the regulated introns
      are spliced out, thus allowing the accumulation of translation-competent mRNAs in
      the cytoplasm. We propose that this mechanism counters ectopic and precocious
      expression of functionally linked neuron-specific genes and ensures their
      coherent activation in the appropriate developmental context.

PMID- 22661232
TI  - Shh maintains dermal papilla identity and hair morphogenesis via a Noggin-Shh
      regulatory loop.
AB  - During hair follicle morphogenesis, dermal papillae (DPs) function as mesenchymal
      signaling centers that cross-talk with overlying epithelium to regulate
      morphogenesis. While the DP regulates hair follicle formation, relatively little
      is known about the molecular basis of DP formation. The morphogen Sonic hedgehog
      (Shh) is known for regulating hair follicle epithelial growth, with excessive
      signaling resulting in basal cell carcinomas. Here, we investigate how dermal
      specific Shh signaling contributes to DP formation and hair growth. Using a Cre
      lox genetic model and RNAi in hair follicle reconstitution assays, we demonstrate
      that dermal Smoothened (Smo) loss of function results in the loss of the DP
      precursor, the dermal condensate, and a stage 2 hair follicle arrest phenotype
      reminiscent of Shh(-/-) skin. Surprisingly, dermal Smo does not regulate cell
      survival or epithelial proliferation. Rather, molecular screening and
      immunostaining studies reveal that dermal Shh signaling controls the expression
      of a subset of DP-specific signature genes. Using a hairpin/cDNA lentiviral
      system, we show that overexpression of the Shh-dependent gene Noggin, but not
      Sox2 or Sox18, can partially rescue the dermal Smo knockdown hair follicle
      phenotype by increasing the expression of epithelial Shh. Our findings suggest
      that dermal Shh signaling regulates specific DP signatures to maintain DP
      maturation while maintaining a reciprocal Shh-Noggin signaling loop to drive hair
      follicle morphogenesis.

PMID- 22661234
TI  - Good brace compliance reduced curve progression and surgical rates in patients
      with idiopathic scoliosis.
AB  - PURPOSE: To examine the association between brace compliance and outcome.
      PATIENTS AND METHODS: 495 (457 females) patients with late onset juvenile and
      adolescent idiopathic scoliosis were examined prospectively before bracing and at
      least 2 years after brace weaning. One spine surgeon examined all patients. 381
      (353 females) answered a standardised questionnaire and 355 had radiological
      examination after median 24 years. Compliance was defined as brace wear >20 h
      daily until weaning. Main outcomes were curve progression and surgery. RESULTS:
      At weaning, 76/389 compliers and 59/106 non-compliers had curve progression >=6
      degrees  (OR 5.2, 95 % CI 3.3-8.2). At long-term the numbers were 68/284 and
      46/71 (OR 5.8, 95 % CI 3.3-10.2), 10/284 versus 17/71 had been operated (OR 8.6,
      95 % CI 3.7-19.9). CONCLUSION: We conclude that the risk for curve progression
      and surgery are reduced in patients with good brace compliance.

PMID- 22661236
TI  - How type I interferons shape myeloid cell function in CNS autoimmunity.
AB  - The precise mechanisms underlying the effects of IFN-I in CNS autoimmunity remain
      poorly understood despite the long-standing use of these cytokines as first-line
      disease-modifying drugs in the treatment of RRMS, a chronic demyelinating CNS
      autoimmune disease. Systemic use of IFN-I results in pleiotropic immunomodulation
      linking the innate and adaptive immune responses. Recent research has
      demonstrated that in the setting of CNS autoimmunity, IFNs-I have multiple
      effects on myeloid cell subsets, such as circulating monocytes, granulocytes,
      DCs, and tissue macrophages, such as microglia. These diverse effects include
      changes in cell activation, maturation, antigen presentation, and cytokine
      production, thus influencing T cell differentiation and expansion, as well as the
      regulation of executive functions, such as apoptosis and phagocytosis. Moreover,
      current data suggest that the engagement of the IFNAR on myeloid cells changes
      the activation status of the inflammasome in a cell type-specific manner. Whereas
      most reports support primarily immune-suppressive effects of IFN-I on myeloid
      cells, endogenously produced, exogenously induced, and peripherally administered
      IFNs-I exert complex differential spatial effects during CNS autoimmune
      inflammation. Clearly characterizing the molecular and cellular basis of these
      effects promises to yield viable targets for a more directed, localized, cell
      type-specific IFN-I-based therapeutic approach. This kind of approach would allow
      for replacing the current treatment strategy in MS of broadly and unselectively
      altering all immune responses, regardless of their beneficial or detrimental
      nature.

PMID- 22661233
TI  - Platelet-derived growth factor receptors differentially inform intertumoral and
      intratumoral heterogeneity.
AB  - Growth factor-mediated proliferation and self-renewal maintain tissue-specific
      stem cells and are frequently dysregulated in cancers. Platelet-derived growth
      factor (PDGF) ligands and receptors (PDGFRs) are commonly overexpressed in
      gliomas and initiate tumors, as proven in genetically engineered models. While
      PDGFRalpha alterations inform intertumoral heterogeneity toward a proneural
      glioblastoma (GBM) subtype, we interrogated the role of PDGFRs in intratumoral
      GBM heterogeneity. We found that PDGFRalpha is expressed only in a subset of
      GBMs, while PDGFRbeta is more commonly expressed in tumors but is preferentially
      expressed by self-renewing tumorigenic GBM stem cells (GSCs). Genetic or
      pharmacological targeting of PDGFRbeta (but not PDGFRalpha) attenuated GSC self
      renewal, survival, tumor growth, and invasion. PDGFRbeta inhibition decreased
      activation of the cancer stem cell signaling node STAT3, while constitutively
      active STAT3 rescued the loss of GSC self-renewal caused by PDGFRbeta targeting.
      In silico survival analysis demonstrated that PDGFRB informed poor prognosis,
      while PDGFRA was a positive prognostic factor. Our results may explain mixed
      clinical responses of anti-PDGFR-based approaches and suggest the need for
      integration of models of cancer as an organ system into development of cancer
      therapies.

PMID- 22661237
TI  - The second international conference "genetics of aging and longevity".

PMID- 22661238
TI  - Integrative medicine as adjunct therapy in the treatment of atopic dermatitis-
      the role of traditional Chinese medicine, dietary supplements, and other
      modalities.
AB  - Atopic dermatitis (AD) is becoming increasingly prevalent in the pediatric
      population, with rates reportedly as high as 18-25 %. Westernized medicine has
      traditionally used a combination of emollients, antihistamines, corticosteroids,
      and immunomodulating agents to combat this often frustrating disease. Of late,
      integrative medicine has become the subject of more research as concerns grow
      regarding prolonged use of corticosteroids and their side effects in pediatric
      patients. Probiotics have been extensively studied to define their role in the
      treatment and prevention of AD in children. Unfortunately, results are varying
      showing significant improvement in some patients but not all. With regard to
      prevention, studies show that the use of probiotics during pregnancy does
      decrease the incidence of AD in children. Prebiotics and synbiotics are also a
      conceivable option for prevention of AD. A number of studies on Chinese herbal
      medicine have been performed, with a collective result of symptom improvement and
      decreased levels of inflammatory cytokines. However, there were reports of
      asymptomatic transaminitis in a few patients that warrant further testing. While
      the herbs tested in more recent randomized clinical trials were free from
      corticosteroids, a previous study showed high levels of dexamethasone in
      unlabeled herbal eczema creams. Vitamins and minerals have also been suggested as
      an alternative treatment of AD. Studies however have not yet demonstrated
      improvement of AD with vitamin or mineral supplementation. Topical vitamin B(12)
      is the exception to this; however, no topical vitamin B(12) preparation is
      available for use. Finally, relaxation techniques are also being investigated as
      adjunctive methods of treatment, but well-designed scientific studies are
      lacking.

PMID- 22661239
TI  - HSP-4 endoplasmic reticulum (ER) stress pathway is not activated in a C. elegans
      model of ethanol intoxication and withdrawal.
AB  - Acute and chronic exposure of Caenorhabditis elegans to concentrations of ethanol
      in the range 250-350 mM elicits distinct behaviours. Previous genetic analysis
      highlights specific neurobiological substrates for these effects. However,
      ethanol may also elicit cellular stress responses which may contribute to the
      repertoire of ethanol-induced behaviours. Here, we have studied the effect of
      ethanol on an important arm of the cellular stress pathways, which emanates from
      the endoplasmic reticulum (ER) in response to several conditions including heat
      shock and chemical or genetic perturbations that lead to protein misfolding. HSP
      4 is a heat shock protein and homologue of mammalian BiP. It is a pivotal
      upstream component of the ER stress response. Therefore, we used a C. elegans
      heat shock protein mutant, hsp-4, and a strain carrying a transcriptional
      reporter, Phsp-4::gfp, to test the role of the ER following chronic ethanol
      conditioning. We found no evidence for an overt ER response during acute or
      prolonged exposure to concentrations of ethanol that lead to defined ethanol
      induced behaviours. Furthermore, whilst hsp-4 was strongly induced by
      tunicamycin, pre-exposure of C. elegans to low doses of tunicamycin followed by
      ethanol was not sufficient to induce an additive ER stress response. Behavioural
      analysis of an hsp-4 mutant indicated no difference compared to wild type in
      susceptibility to ethanol intoxication and withdrawal. There is a clear precedent
      for a significance of ER stress pathways particularly in clinical conditions
      associated with toxic or pathological effects of high doses of alcohol
      consumption. The concentrations of ethanol used in this C. elegans study equate
      to the highest blood alcohol levels measured in patients with chronic alcohol
      dependency. Taken together, these observations imply that the classic ER stress
      pathway in C. elegans is relatively refractory to induction by ethanol.

PMID- 22661240
TI  - Spontaneous rectovaginal fistula during bevacizumab therapy for colon cancer.

PMID- 22661241
TI  - Enhanced bioavailability and cysticidal effect of three mebendazole-oil
      preparations in mice infected with secondary cysts of Echinococcus granulosus.
AB  - The aim of the present study is to explore the possibility to increase the
      efficacy of mebendazole (MBZ) against secondary cysts of Echinococcus granulosus
      harbored in mice by augmenting the solubility and bioavailability of the drug.
      Firstly, the saturated solubility of MBZ in nine kinds of oil was determined by
      high performance liquid chromatography (HPLC), and MBZ was found exhibiting the
      highest, secondary, and lowest solubility in oleic acid (OA), glycerol trioleate
      (GT), and soybean oil (SB), respectively. Secondly, MBZ-OA suspension, MBZ-GT
      suspension, MBZ-SB suspension, and MBZ suspended in 1 % tragacanth (MBZ-1 %
      tragacanth) were selected for further studies on pharmacokinetics and
      experimental therapy in mice. Four groups of mice were treated orally with one of
      aforementioned four MBZ preparations at a single dose of 25 mg/kg, and
      concentrations of MBZ in plasma obtained from each mouse at various intervals
      within 24 h postadministration were determined by HPLC. The major pharmacokinetic
      parameters calculated by MBZ plasma concentration-time curve demonstrated that
      the peak concentration of the drug (C (max) ) values obtained from three MBZ-oil
      preparation groups was 1.6-2.8 times higher than that of MBZ-1 % tragacanth
      group. The same was true that the area under the drug concentration-time curve
      (AUC(0-infinity)) values of 19.8 (2.5)-28.2 (2.5) MUg/ml * h revealed in the
      three MBZ-oil preparation groups was significantly higher than that of 11.6 (2.0)
      MUg/ml * h in MBZ-1 % tragacanth group, and the bioavailability of the three MBZ
      oil preparation groups was 71-143 % higher than that of MBZ-1 % tragacanth group.
      In mice infected with secondary cysts of E. granulosus for 8 months treated
      orally with MBZ-1 % tragacanth at a daily dose of 25 mg/kg for 14 consecutive
      days, the mean cyst weight was lower than that of untreated control, but the
      difference was not statistically significant with cyst weight reduction of 48 %.
      When the infected mice received three MBZ-oil preparations at the same oral dose
      schedule as aforementioned, the mean cyst weights were significantly lower than
      those in MBZ-1 % tragacanth group or control group with cyst weight reductions of
      71.2-84.7 %. The results indicate that the solubility of MBZ in oils may increase
      to various degrees according to the kinds of oil used. Meanwhile, three MBZ-oil
      (OA, GT, and SB) preparations administered orally to mice not only improve the
      bioavailability of MBZ relative to that of MBZ suspended in 1 % tragacanth, but
      their effects against hydatid cysts also significantly enhance.

PMID- 22661242
TI  - Update on food allergy in adults.
AB  - Though much has been studied and written about food allergy, the majority of the
      available literature focuses on food allergies in the pediatric population.
      Unfortunately, it is likely that in regard to food allergies, adults are not just
      big children, and extrapolating findings from pediatric to adult patient
      populations might lead to erroneous assumptions. Thus, it is important to
      validate the correlation between pediatric and adult data, gather data regarding
      adult food allergy and understand the specific nuances of subsets of adults to
      better treat their food allergy. This review was conducted by identifying
      potentially relevant studies regarding food allergies in adults through
      electronic databases, including PubMed, Medline, and Google Scholar. The search
      terms included "allergy", "food" and "adults". Parameters of 19+ years of age
      were added to search terms and all journals were written in or translated to
      English. From these search results, focus was placed on studies from 2010 to
      2012. This systematic update on food allergy in adults found that the evidence
      regarding prevalence, diagnosis and management of food allergies is very limited,
      with the majority of data derived from children and young adults.

PMID- 22661243
TI  - omega-3 polyunsaturated fatty acid supplementation does not influence body
      composition, insulin resistance, and lipemia in women with type 2 diabetes and
      obesity.
AB  - To evaluate the influence of omega-3 polyunsaturated fatty acid (omega-3 PUFA)
      supplementation on body composition, insulin resistance, and lipemia of women
      with type 2 diabetes, the authors evaluated 41 women (60.64 +/- 7.82 years) with
      high blood pressure and diabetes mellitus in a randomized and single-blind
      longitudinal intervention study. The women were divided into 3 groups: GA (2.5
      g/d fish oil), GB (1.5 g/d fish oil), and GC (control). The capsules with the
      supplement contained 21.9% of eicosapentaenoic acid and 14.1% of docosapentaenoic
      acid. Biochemical (glucose, glycated hemoglobin, total and fractional
      cholesterol, triglycerides, and insulin) and anthropometric (body mass, stature,
      waist circumference [WC], and body composition) evaluations were performed before
      and after the 30 days of intervention. Homeostasis model assessment-insulin
      resistance and the Quantitative Insulin Sensitivity Check Index were used to
      evaluate the insulin resistance and insulin sensitivity (IS), respectively. GB
      presented a greater loss of body mass and WC (P < .05), greater frequency of
      glycemic and total cholesterol reduction, and an increase of high-density
      lipoprotein cholesterol compared with GA. Thus, a high dose of omega-3 PUFA can
      reduce IS. A lower dose of omega-3 PUFA positively influenced body composition
      and lipid metabolism.

PMID- 22661244
TI  - Injectable thermogelling chitosan for the local delivery of bone morphogenetic
      protein.
AB  - The aim of the present study was to evaluate the in vivo biocompatibility of
      injectable thermo gelling chitosan-ammonium hydrogen phosphate solution (chitosan
      AHP) and its efficacy to deliver recombinant human bone morphogenetic protein-2
      (rhBMP-2) in a bioactive form. The thermogel showed a typical foreign body
      response upon subcutaneous implantation surrounded by a fibrous capsule. Even at
      4 and 8 weeks post implantation, significant neutrophil infiltration was observed
      within the gel. Chitosan-AHP gel retained most of the loaded rhBMP-2 after a
      small initial release. The bioactivity of the released protein was demonstrated
      in vitro by the increase in alkaline phosphatase activity of mouse pre osteoblast
      cells (MC3T3-E1). Histological and micro-computed tomography (MUCT) evaluation
      showed evidence of ectopic bone formation upon 4 MUg/mL rhBMP-2 loaded chitosan
      AHP injection. The study demonstrated a neutrophil mediated local tissue response
      to chitosan-AHP gel and its ability to encapsulate and maintain the bioactivity
      of rhBMP-2.

PMID- 22661245
TI  - Grafting of poly(ethylene glycol) monoacrylates on polycarbonateurethane by UV
      initiated polymerization for improving hemocompatibility.
AB  - Poly(ethylene glycol) monoacrylates (PEGMAs) with a molecular weight between 400
      and 1,000 g mol(-1) were grafted by ultraviolet initiated photopolymerization on
      the surface of polycarbonateurethane (PCU) for increasing its hydrophilicity and
      improving its hemocompatibility. The surface-grafted PCU films were characterized
      by Fourier transformation infrared spectroscopy, X-ray photoelectron
      spectroscopy, water contact angle, scanning electron microscopy (SEM) and atomic
      force microscopy measurements. The surface properties of the modified films were
      studied in dry and wetted state. Blood compatibility of the surfaces was
      evaluated by platelet adhesion tests and adhered platelets were determined by
      SEM. The results showed that the hydrophilicity of the films had been increased
      significantly by grafting PEGMAs, and platelets adhesion onto the film surface
      was obviously suppressed. Furthermore, the molecular weight of PEGMAs had a great
      effect on the hydrophilicity and hemocompatibility of the PCU films after surface
      modification and increased with increasing molecular weight of PEGMAs.

PMID- 22661246
TI  - Hyaluronic acid/mildly crosslinked alginate hydrogel as an injectable tissue
      adhesion barrier.
AB  - Although hyaluronic acid (HA) has been conventionally utilized as a tissue
      adhesion barrier material, its rapid clearance in the body still remains as a big
      challenge in the clinical practice. In this study, we prepared a hydrogel of HA
      embedded in mildly crosslinked alginate (HA/mcALG hydrogel), which is injectable,
      easily covers injured tissues, and remains stably at the applied site during
      wound healing (by muco-adhesive HA embedded in the network structure of the mcALG
      hydrogel). The HA/mcALG hydrogel was highly effective for the prevention of
      peritoneal tissue adhesion compared to HA and mcALG hydrogels, and did not lead
      to any abnormal tissue responses during wound healing. The HA/mcALG hydrogel can
      be a good candidate as an injectable tissue adhesion barrier for clinical
      applications.

PMID- 22661247
TI  - Single step preparation of nanosilver loaded calcium phosphate by low temperature
      co-conversion process.
AB  - The preparation and characterization of nanosilver loaded calcium phosphate
      aiming to enhance the bactericidal performance by a single step co-conversion
      technique using low temperature ion exchange phosphorization in combination with
      Tollen's reaction were performed. Silver nitrate was used as a silver ion supply
      source (0.001-0.1 M) and glucose was employed as a reducing agent. After
      conversion, surface and shell zones of all samples comprised hydroxyapatite and
      metallic silver as the main phases regardless of silver nitrate concentration.
      However, hydroxyapatite, residual calcium sulfate and monetite were found in the
      core zone when using silver nitrate concentration lower than 0.1 M. The
      microstructure of all samples comprised the distribution of spherical-shaped
      silver nanoparticles within the cluster of calcium phosphate nanocrystals. Total
      silver content (range, 0.09-6.5 %) in the converted samples was found to linearly
      increase with increasing silver nitrate content. Flexural modulus and strength of
      converted samples generally decreased with increasing silver content. Effective
      antibacterial activity of two selected samples (0.001 and 0.005 M AgNO(3))
      against two bacterial strains (Pseudomonas aeruginosa and Staphylococcus aureus)
      was observed. Cytotoxic potentials by MTT assay of both samples were observed at
      24 and 48 h extraction respectively.

PMID- 22661248
TI  - Enhancement of nerve regeneration along a chitosan conduit combined with bone
      marrow mesenchymal stem cells.
AB  - Many studies have been dedicated to the development of scaffolds for improving
      post-traumatic nerve regeneration with different biomaterials. Nerve autografting
      is the most common surgical procedure currently used to repair nerve defects as a
      gold standard. To address the disadvantages of limited availability of donor
      nerves and donor site morbidity, we have fabricated chitosan conduits and seeded
      them combined with bone marrow mesenchymal stem cells (BMSCs) as an alternative.
      The conduits were tested for efficacy in bridging the critical gap (8 mm) in
      sciatic nerves of adult rats, which including sciatic nerve function index (SFI),
      ethology observation, histologic detection, immunohistochemistry detection. The
      BMSCs were tested for survival rate and differentiation by fluorescence labeling.
      Six weeks after operation, the SFI, average regenerated fiber density, and fiber
      diameter in nerves bridged with BMSCs were similar to those treated with
      autograft, but significantly higher than those bridged with chitosan conduits
      only (P < 0.05) because of the differentiation of BMSCs. Evidence is thus
      provided to support the effect of using multi-channel chitosan conduits seeded
      with BMSCs to treat critical defects in peripheral nerves. This provides the
      basis to pursue chitosan and BMSCs combination is an effective method to improve
      the nerve healing, which may be used as an alternative to the conventional nerve
      autografts.

PMID- 22661249
TI  - Influence of sodium hypochlorite treatment of electropolished and
      magnetoelectropolished nitinol surfaces on adhesion and proliferation of MC3T3
      pre-osteoblast cells.
AB  - The influence of 6 % sodium hypochlorite (NaClO) treatment on adhesion and
      proliferation of MC3T3 pre-osteoblast cells seeded on electropolished (EP) and
      magnetoelectropolished (MEP) nitinol surfaces were investigated. The chemistry,
      topography, roughness, surface energy, wettability of EP and MEP nitinol surfaces
      before and after NaClO treatment were studied with X-ray photoelectron
      spectroscopy (XPS), profilometry, and contact angle meter. In vitro interaction
      of osteoblast cell and NaClO treated EP and MEP nitinol surfaces were assessed
      after 3 days of incubation by scanning electron microscopy. The XPS analysis
      shows that NaClO treatment increases oxygen content especially in subsurface
      oxide layer of EP and MEP nitinol. The changes of both basic components of
      nitinol, namely nickel and titanium in oxide layer, were negligible. The NaClO
      treatment did not influence physico-morphological surface properties of EP and
      MEP nitinol to a big extent. The osteoblast cells show remarkable adherence and
      proliferation improvement on NaClO treated EP and MEP nitinol surfaces. After 3
      days of incubation they show almost total confluence on both NaClO treated
      surfaces. The present study shows that NaClO treatment of EP and MEP nitinol
      surfaces alters oxide layer by enriching it in oxygen and by this improves bone
      cell-nitinol interaction.

PMID- 22661250
TI  - Longer-term outcomes of nutritional management of Crohn's disease in children.
AB  - BACKGROUND: While the short-term benefits of exclusive enteral nutrition (EEN)
      for induction of remission in children with Crohn's disease (CD) are well
      documented, the longer-term outcomes are less clear. AIM: This retrospective
      study aimed to ascertain the outcomes for up to 24 months following EEN in a
      group of children with CD. METHODS: Children treated with EEN as initial therapy
      for newly diagnosed CD over a 5-year period were identified. Details of disease
      activity, growth, and drug requirements over the period of follow-up were noted.
      Outcomes in children managed with EEN were compared to a group of children
      initially treated with corticosteroids. RESULTS: Over this time period, 31
      children were treated with EEN and 26 with corticosteroids. Twenty-six (84 %) of
      the 31 children treated with EEN entered remission. Children treated with EEN
      exhibited lower pediatric Crohn's disease activity index (PCDAI) scores at 6
      months (p = 0.02) and received lower cumulative doses of steroids over the study
      period (p < 0.0001) than the group treated with corticosteroids. Height
      increments over 24 months were greater in the EEN group (p = 0.01). Although the
      median times to relapse were the same, the EEN group had a lower incidence of
      relapse in each time interval and survival curve analysis showed lower risk of
      relapse (p = 0.008). CONCLUSIONS: EEN lead to multiple benefits beyond the
      initial period of inducing remission for these children, with positive outcomes
      over 2 years from diagnosis. Of particular clinical relevance to growing children
      was the reduced exposure to corticosteroids.

PMID- 22661251
TI  - Low yield of significant findings on endoscopic retrograde
      cholangiopancreatography in patients with pancreatobiliary pain and no objective
      findings.
AB  - BACKGROUND: Due to the challenging nature of the type III sphincter of the Oddi
      dysfunction (SOD) patient, the suspected low diagnostic yield from endoscopic
      retrograde cholangiopancreatography (ERCP), the high complication rate, and the
      potential for litigation it is surprising that diagnostic ERCP continues to be
      performed in this patient population. AIMS: The purpose of this study was to
      determine the incidence of significant findings on ERCP alone in patients with
      disabling abdominal pain of suspected pancreatobiliary origin and no objective
      findings. METHODS: Entry criteria of this study included: (1) ERCP with attempt
      at visualization of both the biliary tree and pancreatic duct, (2) suspected of
      having abdominal pain of pancreatobiliary origin, (3) biliary or pancreatic type
      III by the modified Geenen-Hogan classification, (4) never undergone
      sphincterotomy, (5) attempted manometry of both sphincters. A total of 265
      patients met entry criteria. RESULTS: Significant findings were found in seven
      patients (2.6 %): choledococoele (1), anomalous pancreatobiliary ductal union
      (2), mild-moderate chronic pancreatitis (2), and pancreatic duct filling defect
      suspicious for IPMN (2). Potentially significant in 25 patients (9.4 %) were:
      equivocal chronic pancreatitis (1), incomplete (4) and complete pancreas divisum
      (20). SOD was diagnosed in 77.7 %. 11.3 % had undergone a previous diagnostic
      ERCP. CONCLUSION: ERCP in this high-risk population requires detailed informed
      consent, availability of SOM to increase the diagnostic yield, and skills in
      placing prophylactic pancreatic stents. It is our belief that patients without
      objective findings of pancreatobiliary disease that would explain their
      subjective complaints should not undergo diagnostic ERCP.

PMID- 22661252
TI  - Use of SPECT to detect changes in diastolic and coronary reserve in patients with
      obstructive sleep apnea.
AB  - PURPOSE: To assess diastolic function and coronary artery reserve in patients
      with obstructive sleep apnea (OSA) using single-photon emission computer
      tomography (SPECT). METHODS: Patients with OSA who had normal
      echocardiograph/electrocardiogram findings were divided into three groups based
      on OSA severity: mild (n = 15), moderate (n = 13), or severe (n = 18). A control
      group of participants without OSA (n = 17) was included. SPECT (with technetium
      99 m-labeled red blood cells) was performed after the induction of cardiac stress
      by injection of dobutamine. The following ventricular parameters were determined:
      left ventricular ejection fraction, peak filling rate (PFR), peak ejection rate,
      1/3 filling fraction (1/3FF), and regional ejection fractions (rEF). RESULTS: The
      median ages of OSA and control participants were 45.0 and 51.0 years,
      respectively. Median apnea-hypopnea index scores were 3.3, 9.1, 38.5, and 65.2
      for the control, mild OSA, moderate OSA, and severe OSA groups, respectively.
      Post-stress, 1/3FF was significantly lower in the overall OSA group compared with
      the control group (P < 0.05). PFR was significantly lower in the overall OSA
      group compared with the control group (P < 0.05) and was significantly lower in
      the severe OSA group compared with the mild OSA group. Regional ejection
      fractions rEF3 (cardiac apex and a small part of the inferior wall) and rEF4
      (anteroseptal wall) were significantly lower in the overall OSA group compared
      with the control group, suggesting decreased coronary artery reserve. CONCLUSION:
      Our findings suggest that SPECT can be used to detect abnormalities in diastolic
      function and coronary reserve in patients with OSA who have normal
      electrocardiogram or echocardiograph findings. SPECT may be useful for the early
      detection of cardiovascular disease in patients with OSA.

PMID- 22661253
TI  - The Minority Training Program in Cancer Control Research: impact and outcome over
      12 years.
AB  - The Minority Training Program in Cancer Control Research (MTPCCR) encourages
      underrepresented master's level students and professionals in the social,
      behavioral, and public health sciences to pursue doctoral training and careers in
      cancer disparities research. This paper reports new data on the program outcome
      after 12 years. A web-based survey was sent to all 462 program alumni. The
      questions addressed current academic status and plans, job status and plans,
      research focus, and influence of the MTPCCR. The survey response rate was 79 %.
      Overall, 30 % of alumni are enrolled in or have completed doctoral programs; 88 %
      of whom report involvement in research related to cancer. Scaled and open-ended
      responses indicate a strong influence of the program on doctoral program
      enrollment and cancer focus. The MTPCCR model is successful because it targets
      underrepresented minorities who are capable of doctoral studies but have not yet
      chosen that path.

PMID- 22661255
TI  - Association between transforming growth factor-alpha polymorphism and ankylosing
      spondylitis: a meta-analysis update.
AB  - OBJECTIVES: The reported results of the relationship between genetic
      polymorphisms of tumor necrosis factor (TNF)-alpha -238, -308 locus and
      ankylosing spondylitis (AS) susceptibility are not always consistent. This
      article aims to perform a meta-analysis to collect all the relevant studies to
      date to further clarify the relationship between those genetic polymorphisms and
      AS. METHODS: A computer search was carried out up to September 2011 for
      literature pertaining to AS and TNF-alpha polymorphisms. RESULTS: Twenty-two
      articles were included, with 2,506 cases of AS and 3,023 normal controls. We
      searched for genotypes A allele vs. G allele, AA vs. GG + GA, and GA + AA vs. GG
      in a fixed/random-effects model. The effect summary odds ratios (ORs) and 95 %
      confidence intervals (CIs) were obtained, which shows there was no association
      between genetic polymorphisms and AS. As the heterogeneity was observed, in a
      subgroup analysis by ethnicity, the degree of risk of two genes with AS
      susceptibility was similar in populations of European and Asian origin. For the
      human leukocyte antigen (HLA)-B27+ population, results were not statistically
      significant. CONCLUSION: ORs of various comparisons indicate that there is no
      association between TNF-alpha -238, -308 polymorphisms and AS susceptibility in
      the overall population and in the subgroup of Asian and non-Asian descent.

PMID- 22661254
TI  - Insulin receptor beta-subunit haploinsufficiency impairs hippocampal late-phase
      LTP and recognition memory.
AB  - The insulin receptor (IR) is a protein tyrosine kinase playing a pivotal role in
      the regulation of peripheral glucose metabolism and energy homoeostasis. IRs are
      also abundantly distributed in the cerebral cortex and hippocampus, where they
      regulate synaptic activity required for learning and memory. As the major
      anabolic hormone in mammals, insulin stimulates protein synthesis partially
      through the activation of the PI3K/Akt/mTOR pathway, playing fundamental roles in
      neuronal development, synaptic plasticity and memory. Here, by means of a
      multidisciplinary approach, we report that long-term synaptic plasticity and
      recognition memory are impaired in IR beta-subunit heterozygous mice. Since IR
      expression is diminished in type-2 diabetes as well as in Alzheimer's disease
      (AD) patients, these data may provide a mechanistic link between insulin
      resistance, impaired synaptic transmission and cognitive decline in humans with
      metabolic disorders.

PMID- 22661259
TI  - Site-specific recombination systems in filamentous phages.
AB  - Since the discovery of the integration mechanism of the filamentous phage CTXphi
      of Vibrio cholerae, integrating filamentous phages have been discovered to be
      more abundant and diverse than previously recognized. However, the integration
      systems of filamentous phages have not been fully investigated. The present
      review provides a short overview on the different strategies employed by
      filamentous bacteriophages for integration into the host chromosome. This is the
      first review to describe the diversity of site-specific recombination in
      filamentous phages.

PMID- 22661260
TI  - The investigation of the possibility for using some wild and cultivated plants as
      hyperaccumulators of heavy metals from contaminated soil.
AB  - The copper production in Bor (East Serbia) during the last 100 years presents an
      important source of the pollution of environment. Dust, waste waters, tailing,
      and air pollutants influence the quality of soil, water, and air. Over 2,000 ha
      of fertile soil have been damaged by the flotation tailing from Bor's facilities.
      The goal of the present work has been to determine the content of Pb, Cu, and Fe
      in wild plants (17 species) naturally growing in the damaged soil and in fodder
      crops (nine species) planted at the same place. The content of Pb, Cu, and Fe has
      been analyzed in damaged soil as well. This study has also searched for native
      (wild) and cultivated plants which are able to grow in contaminated soil in the
      area of the intense industrial activity of copper production in Bor, which means
      that they can accumulate and tolerate heavy metals in their above-ground tissues.
      It has been found out that the content of all metals in contaminated soil
      decreases considerably at the end of the experiment. As it has been expected, all
      plant species could accumulate investigated metals. All tested plants, both wild
      growing and cultivated plants, seem to be quite healthy on the substrate which
      contained extremely high concentrations of copper.

PMID- 22661261
TI  - Biosorption of arsenic from aqueous solution using dye waste.
AB  - The purpose of this study is to examine on removal of arsenic from water by
      biosorption through potential application of herbal dye wastes. Four different
      flower dye residues (after extraction of natural dye) viz. Hibiscus rosasinensis,
      Rosa rosa, Tagetes erecta, and Canna indica were utilized successfully for the
      removal of arsenic from aqueous solution. Batch studies were carried out for
      various parameters viz. pH, sorbent dose, contact time, initial metal ion
      concentration, and temperature. Data were utilized for isothermal, kinetic, and
      thermodynamic studies. Scanning electron microscopy (SEM), energy-dispersive x
      ray spectroscopy (EDAX), and Fourier transform infrared (FTIR) analyses of
      biomass were performed. The results showed that 1 g/100 ml for 5.0-5.5 h contact
      time at pH 6.0-7.5 with agitation rate 150 rpm provided 98, 96, 92, and 85 %
      maximum absorption of arsenic by R. rosa, H. rosasinensis, T. erecta, and C.
      indica, respectively, at initial concentration of 500 ppb. Data followed Langmuir
      isotherm showing sorption to be monolayer on heterogeneous surface of biosorbent.
      Negative values of DeltaG degrees  indicated spontaneous nature, whereas DeltaH
      degrees  indicates exothermic nature of system followed by pseudo-first-order
      adsorption kinetics. FTIR results showed apparent changes in functional group
      regions after metal chelation. SEM and EDAX analyses showed the changes in
      surface morphology of all test biosorbents. Herbal dye wastes, used as
      biosorbent, exhibited significant (85-98 %) removal of arsenic from aqueous
      solution. Hence, these biosorbents are cost-effective, easily available, eco
      friendly, and comparatively more effective than other biosorbents already in use.
      These may be used to remove arsenic and other toxic metals from water.

PMID- 22661262
TI  - Scavenging of BHCs and DDTs from soil by thermal desorption and solvent washing.
AB  - Intensive remediation of abandoned former organochlorine pesticides (OCPs)
      manufacturing areas is necessary because the central and surrounding soils
      contaminated by OCPs are harmful to crop production and food safety.
      Organochlorine and its residues are persistent in environments and difficult to
      remove from contaminated soils due to their low solubility and higher sorption to
      the soils. We performed a comprehensive study on the remediation of OCPs
      contaminated soils using thermal desorption technique and solvent washing
      approaches. The tested soil was thermally treated at 225, 325, 400, and 500 
      degrees C for 10, 20, 30, 45, 60, and 90 min, respectively. In addition, we
      tested soil washing with several organic solvents including n-alcohols and
      surfactants. The optimal ratio of soil/solvent was tested, and the recycling of
      used ethanol was investigated. Finally, activities of polyphenol oxidase (PPO),
      urease (URE), alkaline phosphatase, acid phosphatase (ACP), and invertase (INV)
      were assayed in the treated soils. The tested soil was thermally treated at 500 
      degrees C for 30 min, and the concentration of contaminants in soil was decreased
      from 3,115.77 to 0.33 mg kg(-1). The thermal desorption in soil was governed by
      the first-order kinetics model. For the chemical washing experiment, ethanol
      showed a higher efficiency than any other solvent. Using a 1:20 ratio of
      soil/solvent, the maximum removal of OCPs was achieved within 15 min. Under this
      condition, approximately 87 % of OCPs was removed from the soils. More than 90 %
      of ethanol in the spent wash fluid could be recovered. Activities of some enzymes
      in soils were increased after ethanol treatment. But ALP, ACP, and INV activities
      were decreased and PPO and URE showed slightly higher activities following
      remediation by thermal treatment. Both heating temperature and time were the key
      factors for thermal desorption of OCPs. The n-alcohol solvent showed higher
      removal of OCPs from soils than surfactants. The highly efficient removal of OCPs
      from soil was achieved using ethanol. More than 90 % of ethanol could be
      recovered and be reused following distillation. This study provides a cost
      effective and highly efficient way to remediate the OCPs-contaminated soils.

PMID- 22661263
TI  - Adsorption of Cd to natural biofilms in the presence of EDTA: effect of pH,
      concentration, and component addition sequence.
AB  - Both dissolved organic matters (DOM) and natural biofilms are important
      substances in controlling the behavior of trace metals in natural aquatic
      environments. In this study, ethylenediaminetetraacetic acid (EDTA) was selected
      as a typical DOM to investigate the effect of DOM on the adsorption of trace
      metals to the biofilms in natural waters. The adsorption of Cd to biofilms,
      including adsorption isotherm at a fixed pH (pH = 6.0) and pH-edge adsorption (pH
      ranging from 4.3 to 9.0) with different adsorption sequences, was determined
      without EDTA and in the presence of EDTA ([EDTA] = 0.5 MUmol/L for isotherms
      measurement and [EDTA] = 0.5 and 2.0 MUmol/L for pH-dependent adsorption). The
      presence of EDTA generally decreased the adsorption of Cd, and the effect was
      determined by solution pH, concentration of EDTA, and adsorption sequence. Higher
      concentration or higher pH usually resulted in a more significant decrease. The
      influence of adsorption sequence on the effect of EDTA was insignificant in lower
      pH range, while the adsorption usually decreased in the order of Cd only
      adsorption > Cd first adsorption > EDTA first adsorption ~ simultaneous
      adsorption in higher pH range. The effect of EDTA could be attributed to the
      conversion of Cd speciation, the competition with the biofilms for Cd, and the
      dissolution of Mn oxides from the biofilms. EDTA affected the adsorption of Cd to
      natural biofilms, and the effect could be fairly significant. The role of Mn
      oxides in determining the behavior of trace metals might be underestimated.

PMID- 22661264
TI  - Enhancing a cancer prevention and control curriculum through interactive group
      discussions.
AB  - The Principles and Practice of Cancer Prevention and Control course (Principles
      course) is offered annually by the National Cancer Institute Cancer Prevention
      Fellowship Program. This 4-week postgraduate course covers the spectrum of cancer
      prevention and control research (e.g., epidemiology, laboratory, clinical,
      social, and behavioral sciences) and is open to attendees from medical, academic,
      government, and related institutions across the world. In this report, we
      describe a new addition to the Principles course syllabus, which was exclusively
      a lecture-based format for over 20 years. In 2011, cancer prevention fellows and
      staff designed and implemented small group discussion sessions as part of the
      curriculum. The goals of these sessions were to foster an interactive
      environment, discuss concepts presented during the Principles course, exchange
      ideas, and enhance networking among the course participants and provide a
      teaching and leadership opportunity to current cancer prevention fellows.
      Overall, both the participants and facilitators who returned the evaluation forms
      (n=61/87 and 8/10, respectively) reported a high satisfaction with the experience
      for providing both an opportunity to explore course concepts in a greater detail
      and to network with colleagues. Participants (93%) and facilitators (100%) stated
      that they would like to see this component remain a part of the Principles course
      curriculum, and both groups provided recommendations for the 2012 program. The
      design, implementation, and evaluation of this initial discussion group component
      of the Principles course are described herein. The findings in this report will
      not only inform future discussion group sessions in the Principles course but may
      also be useful to others planning to incorporate group learning into large
      primarily lecture-based courses.

PMID- 22661265
TI  - Maternal high-fat diet is associated with altered pancreatic remodelling in mice
      offspring.
AB  - PURPOSE: To investigate whether a maternal high-fat diet (HF) during pregnancy
      and/or suckling periods predisposes adult C57BL/6 mice offspring to morphological
      pancreatic modifications. METHODS: Male pups were divided into 5 groups: SC
      (standard chow)-from dams fed SC during gestation and lactation, maintaining an
      SC diet from postweaning to adulthood; G-from dams fed HF diets during gestation;
      L-from dams fed HF diets during lactation; GL-from dams fed HF diets during
      gestation and lactation; and GL/HF-from dams fed HF diets during gestation and
      lactation, maintaining an HF diet from postweaning to adulthood. We analysed body
      mass (BM), plasma insulin, pancreas and adipose tissue structures. RESULTS:
      During the entire experiment, the SC group had the lowest BM. However, GL/HF
      offspring were heavier than the other groups. This weight gain was also
      accompanied by adipocyte hypertrophy. At 3 months, G offspring showed an
      increased insulin levels and impairment in carbohydrates metabolism. Furthermore,
      pancreatic islets were hypertrophied in G, GL and GL/HF offspring in comparison
      with SC offspring. CONCLUSION: HF diet administration during the gestation period
      is more harmful than during the lactation period, exerting deleterious effects on
      pancreatic morphology in addition to larger fat deposits in adult mice offspring.

PMID- 22661267
TI  - Wetting, spreading, and adsorption on randomly rough surfaces.
AB  - The wetting properties of solid substrates with customary (i.e., macroscopic)
      random roughness are considered as a function of the microscopic contact angle of
      the wetting liquid and its partial pressure in the surrounding gas phase.
      Analytic expressions are derived which allow for any given lateral correlation
      function and height distribution of the roughness to calculate the wetting phase
      diagram, the adsorption isotherms, and to locate the percolation transition in
      the adsorbed liquid film. Most features turn out to depend only on a few key
      parameters of the roughness, which can be clearly identified. It is shown that a
      first-order transition in the adsorbed film thickness, which we term "Wenzel
      prewetting", occurs generically on typical roughness topographies, but is absent
      on purely Gaussian roughness. It is thereby shown that even subtle deviations
      from Gaussian roughness characteristics may be essential for correctly predicting
      even qualitative aspects of wetting.

PMID- 22661266
TI  - Clinical features of strangulated small bowel obstruction.
AB  - PURPOSE: The causes of strangulated small bowel obstruction (SSBO) include a
      fibrous cord, torsion, and internal hernia. We conducted this study to define the
      clinical features of SSBO. METHODS: We reviewed the clinical course and
      preoperative data of 74 patients treated for SSBO in Kumamoto Regional Medical
      Center between January 2004 and September 2010. RESULTS: Twenty-one patients had
      no history of laparotomy. Computed tomography (CT) showed high positivity (86.3
      %) of closed loops in the involved intestine. Postoperative complications
      developed in 23 patients, representing a morbidity rate of 31.1 %. Forty-four
      patients underwent resection of non-viable small intestine (non-viable group),
      and 30 did not require resection of the intestine (viable group). There were four
      hospital deaths in the non-viable group. The overall mortality rate and the
      mortality rate in the non-viable group were 5.4 and 9.1 %, respectively.
      CONCLUSION: These findings indicate that SSBO can occur without a history of
      laparotomy, CT is useful in its diagnosis, and its associated morbidity and
      mortality are high.

PMID- 22661268
TI  - A toy model of fractal glioma development under RF electric field treatment.
AB  - A toy model for glioma treatment by a radio frequency electric field is
      suggested. This low-intensity, intermediate-frequency alternating electric field
      is known as the tumor-treating field (TTF). In the framework of this model the
      efficiency of this TTF is estimated, and the interplay between the TTF and the
      migration-proliferation dichotomy of cancer cells is considered. The model is
      based on a modification of a comb model for cancer cells, where the migration
      proliferation dichotomy becomes naturally apparent. Considering glioma cancer as
      a fractal dielectric composite of cancer cells and normal tissue cells, a new
      effective mechanism of glioma treatment is suggested in the form of a giant
      enhancement of the TTF. This leads to the irreversible electroporation that may
      be an effective non-invasive method of treating brain cancer.

PMID- 22661270
TI  - Which antithrombin for whom? Identifying the patient population that benefits
      most from novel antithrombin agents.
AB  - Anticoagulation has proven to be a key component in the management of acute
      coronary syndromes (ACS). Pharmacological agents with various modes of action are
      utilized to reduce thrombus development by impairing thrombin formation, platelet
      activation, and platelet aggregation. The optimal management of these patients is
      to achieve maximal anti-ischemic benefit while avoiding bleeding complications.
      Synthetic "novel" agents have been developed to specifically target factor Xa or
      thrombin to achieve this goal. A growing amount of data show that these agents
      provide a net clinical benefit in the setting of stable ischemic heart disease,
      unstable angina, non-ST-elevation myocardial infarction (NSTEMI), and ST
      elevation myocardial infarction (STEMI).

PMID- 22661269
TI  - Involvement of commensal bacteria may lead to dysregulated inflammatory and
      autoimmune responses in a mouse model for chronic nonsuppurative destructive
      cholangitis.
AB  - BACKGROUND: We previously reported a mouse model of primary biliary cirrhosis
      (PBC)-like chronic nonsuppurative destructive cholangitis (CNSDC), in which
      frequent injections of Streptococcus intermedius induced CNSDC and autoantibody
      production. The present study was performed to verify the model by examining 1)
      the reappearance of the PBC-like CNSDC after lymphocyte transfer from model to
      naive mice, 2) the involvement of autophagy, and 3) the influence of the strain
      difference. METHODS: Mice were inoculated with S. intermedius weekly for 8 weeks,
      then sacrificed to obtain samples. Spleen cells obtained from S. intermedius
      inoculated mice were transferred to RAG2(-/-) mice. RESULTS: CNSDC and elevated
      serum level of anti-gp210 titers were observed in S. intermedius-inoculated
      C57BL/6 mice, similar to the results of our previous report using BALB/c mice.
      Portal inflammation was induced in the livers of RAG2(-/-) mice by the transfer
      of spleen cells from S. intermedius-inoculated C57BL/6 mice. Among the
      inflammatory cells in the RAG2(-/-) mice, CD3-positive cells were predominant.
      Autophagosome-like structures were detected histologically, in the cytoplasm of
      infiltrated cells around the bile ducts in the livers of S. intermedius
      inoculated both C57BL/6 and BALB/c mice. In S. intermedius-inoculated C3H/HeJ
      mice, inflammation in the portal area was less extensive than that in the hepatic
      parenchyma. CONCLUSION: Bacterial component(s) and sequentially upregulated
      innate and acquired immune responses, accompanied by autophagy, might trigger
      CNSDC, via autoimmune mechanisms. Throughout the generation of bacteria-triggered
      PBC-like CNSDC, strain difference may influence the response to S. intermedius
      inoculation in the liver.

PMID- 22661271
TI  - Endoscopic mucosal resection of an Epstein-Barr virus-associated
      lymphoepithelioma-like gastric carcinoma.

PMID- 22661273
TI  - Osteopontin contributes to TGF-beta1 mediated hepatic stellate cell activation.
AB  - BACKGROUND AND PURPOSE: Liver fibrosis is characterized by accumulation of
      extracellular matrix. Our previous study found that osteopontin (OPN) increased
      in plasma of cirrhotic patients and indicative of cirrhosis staging. The present
      study was designed to investigate the expression of OPN in liver tissues and
      plasma of cirrhotic patients and further explore the role of OPN in human hepatic
      stellate cell (HSC) activation. METHODS: We used immunohistochemical staining and
      enzyme-linked immunosorbent assay to evaluate the expression level of OPN in
      liver tissues and plasma from cirrhotic patients, respectively. We produced
      lentivirus particles and infected target cell to manipulate OPN expression.
      Infection efficiency was determined by real-time RT-PCR and western blot. Cell
      proliferation was determined using CCK8 assay, and phenotypes of HSC activation
      were determined by real-time RT-PCR. OPN promoter activity was determined by dual
      luciferase reporter assay. RESULTS: We found that OPN expression in human
      cirrhotic liver tissues was upregulated compared to normal controls. In addition,
      its expression correlated with Child-Pugh classification, MELD score and the
      occurrence of complications. We further explored OPN level in patients' plasma
      and showed that its level correlated with transforming growth factor-beta1 (TGF
      beta1). In human HSC cell line LX-2, we found that change of OPN expression level
      could not only affect the proliferation of cells but also the TGF-beta1 mediated
      HSC activation. Moreover, OPN was increased by TGF-beta1 stimulation and
      regulated by TGF-beta1 at transcription level. CONCLUSIONS: OPN is upregulated in
      liver tissues and plasma of cirrhotic patients and promotes TGF-beta1 mediated
      HSC activation.

PMID- 22661274
TI  - Gastroesophageal reflux disease and obesity: not as simple as we may think.

PMID- 22661272
TI  - Non-variceal gastrointestinal bleeding in patients with liver cirrhosis: a
      review.
AB  - BACKGROUND: Non-variceal gastrointestinal (NVGI) bleeding in cirrhosis may be
      associated with life-threatening complications similar to variceal bleeding. AIM:
      To review NVGI bleeding in cirrhosis. METHODS: MEDLINE, Scopus, and ISI Web of
      Knowledge were searched, using the textwords "portal hypertensive gastropathy,"
      "gastric vascular ectasia," "peptic ulcer," "Dieulafoy's," "Mallory-Weiss
      syndrome," "portal hypertensive enteropathy," "portal hypertensive colopathy,"
      "hemorrhoids," and "cirrhosis." RESULTS: Portal hypertensive gastropathy (PHG)
      and gastric vascular ectasia (GVE) are gastric lesions that most commonly present
      as chronic anemia; acute upper GI (UGI) bleeding is a rare manifestation.
      Management of PHG-related bleeding is mainly pharmacological, whereas endoscopic
      intervention is favored in GVE-related bleeding. Shunt therapies or more invasive
      techniques are restricted in refractory cases. Despite its high incidence in
      cirrhotic patients, peptic ulcer accounts for a relatively small proportion of
      UGI bleeding in this patient population. However, in contrary to general
      population, the pathogenetic role of Helicobacter pylori infection remains
      questionable. Finally, other causes of UGI bleeding include Dieulafoy's lesion,
      Mallory-Weiss syndrome, and portal hypertensive enteropathy. The most common non
      variceal endoscopic findings reported in patients with lower gastrointestinal
      bleeding are portal hypertensive colopathy and hemorrhoids. However, the vast
      majority of studies are case reports and, therefore, the incidence, diagnosis,
      and risk of bleeding remain undefined. Endoscopic interventions, shunting
      procedures, and surgical techniques have been described in this setting.
      CONCLUSIONS: The data on NVGI bleeding in liver cirrhosis are surprisingly
      scanty. Large, multicenter epidemiological studies are needed to better assess
      prevalence and incidence and, most importantly, randomized studies should be
      performed to evaluate the success rates of therapeutic algorithms.

PMID- 22661275
TI  - Holiday pains: a case of radiation-induced mesenteric ischemia.

PMID- 22661276
TI  - Evaluating the feasibility of direct peroral cholangioscopy training with an
      endoscopic simulator.
AB  - INTRODUCTION: Direct peroral cholangioscopy (DPOCS) was reported to present
      clinical potential, and creating a target-specific training program for biliary
      endoscopists who lack experience with DPOCS is an important task. METHODS: This
      prospective and observational study used five male domestic pigs. Optimal
      procedures were decided after pilot tests using an in vivo live porcine model. A
      total of three ERCP men were enrolled into the training program. The objective
      parameters, including the rate of success and complications, and the length of
      the procedure, were recorded for each participant. RESULTS: In the training
      program, all the trainees successfully performed DPOCS and biopsies without
      significant complications. Close observation, free discussions, and the sharing
      of experiences helped shorten the total procedure time from 37.3 to 18.5 min.
      CONCLUSIONS: This training program is a feasible approach to help biliary
      endoscopists acquire the experience for DPOCS with the ultrathin endoscope.

PMID- 22661277
TI  - Assessment of endothelial function in patients with nonalcoholic fatty liver
      disease.
AB  - In this study, we aimed to evaluate the endothelial functions in patients with
      nonalcoholic fatty liver disease (NAFLD). In this observational case-control
      study, a total of 51 patients with NAFLD in study group and a total of 21 with
      age- and sex-equivalent individuals in control group were enrolled. In both
      patients and control groups, levels of asymmetric dimethylarginine (ADMA),
      systemic endothelial function (brachial artery flow-mediated dilation) (FMD) and
      carotid artery intima-media thickness (C-IMT) were measured. FMD and C-IMT were
      evaluated by vascular ultrasound. Plasma levels of ADMA were measured by ELISA. C
      IMT was significantly higher in patients with NAFLD group than control group
      (0.67 +/- 0.09 vs. 0.52 +/- 0.11 mm, P < 0.001). The average C-IMT measurements
      were found in groups of control, simple steatosis, and NAFLD with (borderline and
      definite) NASH as 0.52 +/- 0.11, 0.63 +/- 0.07, and 0.68 +/- 0.1 mm,
      respectively. The differences between groups were significant (P < 0.001).
      Measurement of brachial artery FMD was significantly lower in patients with NAFLD
      group compared to control group (7.3 +/- 4.8 vs. 12.5 +/- 7.1 %, P < 0.001). FMD
      measurements in groups of control, the simple steatosis, and NAFLD with NASH as
      12.5 +/- 7.1, 9.64 +/- 6.63, and 7.03 +/- 4.57 %, respectively, and the
      differences were statistically significant (P < 0.001). The increase in C-IMT and
      decrease in FMD was independent from metabolic syndrome and it was also more
      evident in patients with simple steatosis and NASH compared to control group.
      There was no significant difference between the control and NAFLD groups in terms
      of plasma ADMA levels (0.61 +/- 0.11 vs. 0.69 +/- 0.37 MUmol/L, P = 0.209). Our
      data suggested that NAFLD is associated with endothelial dysfunction and
      increased earlier in patients with atherosclerosis compared to control subjects.

PMID- 22661278
TI  - Reduced-intensity modified constraint-induced movement therapy versus
      conventional therapy for upper extremity rehabilitation after stroke: a
      multicenter trial.
AB  - BACKGROUND: Constraint-induced movement therapy (CIMT) is a rehabilitation
      approach for arm paresis consisting of an intensive schedule of treatment (6
      h/d). The high demand of resources for CIMT is a critical issue for its
      implementation in the Italian health system. OBJECTIVE: To compare the effects of
      a reduced-intensity modified CIMT (mCIMT) program that included splinting the
      unaffected arm for 12 hours daily with the effects of a conventional
      rehabilitation program for arm paresis in patients with stroke. METHODS: Sixty
      six participants with hemiparesis (3-24 months poststroke) who could extend the
      wrist and several fingers at least 10 degrees  were randomly assigned to mCIMT or
      conventional rehabilitation. Each group underwent 10 (2 h/d) treatment sessions
      (5 d/wk for 2 weeks). Patients were assessed with the Wolf Motor Function Test
      (WMFT-FA and WMFT-T), the Motor Activity Log (MAL-AOU and MAL-QOM), and the
      Ashworth Scale before and after treatment and 3 months later. RESULTS: Between
      groups analysis showed that the mCIMT group overall had greater improvement than
      the control group in terms of the WMFT-FA (P = .010), MAL-AOU (P < .001), and MAL
      QOM (P < .001). Differences between groups were significant both after treatment
      (P < .01) and at the 3-month follow-up (P < .01), although 40% of participants
      did not complete the 3-month assessment. Furthermore, the mCIMT group showed a
      greater decrease of Ashworth Scale score than the control group at 3 months (P =
      .021). CONCLUSION: Two hours of CIMT may be more effective than conventional
      rehabilitation in improving motor function and use of the paretic arm in patients
      with chronic stroke.

PMID- 22661279
TI  - Accumulation and spatial distribution of Cd, Cr, and Pb in mulberry from
      municipal solid waste compost following application of EDTA and (NH4)2SO4.
AB  - Municipal solid waste compost can be used to cropland as soil amendment to supply
      nutrients and improve soil physical properties. But long-term application of
      municipal solid waste (MSW) compost may result in accumulation of toxic metals in
      amended soil. Phytoremediation, especially phytoextraction, is a novel, cost
      effective, and environmentally friendly approach that uses metal-accumulating
      plants to concentrate and remove metals from contaminated soils.
      Ethylenediaminetetraacetate (EDTA) was applied to metal-contaminated soil to
      increase the mobility and phytoavailability of metals in soil, thereby increasing
      the amount of toxic metals accumulated in the upper parts of phytoextracting
      plants. The objectives of this study were (1) to investigate the accumulation and
      spatial distribution of toxic metals (Cd, Cr, and Pb) in mulberry from MSW
      compost with the application of EDTA and (NH(4))(2)SO(4), (2) to examine the
      effectiveness of EDTA and (NH(4))(2)SO(4) applied together on toxic metals (Cd,
      Cr, and Pb) removal by mulberry under field conditions, and (3) to evaluate the
      potential of mulberry for phytoextraction of toxic metals from MSW compost. The
      tested plant-mulberry had been grown in MSW compost field for 4 years. EDTA
      solution at five rates (0, 50, 100, 50 mmol L(-1) + 1 g L(-1) (NH(4))(2)SO(4),
      and 100 mmol L(-1) + 1 g L(-1) (NH(4))(2)SO(4)) was added into mulberry root
      medium in September 2009. Twenty days later, the plants were harvested and
      separated into six parts according to plant height. Cd, Cr, and Pb contents in
      plant samples and MSW compost were analyzed using an atomic absorption
      spectrophotometer. In the same treatment, Cd, Cr, and Pb concentrations in
      mulberry shoot were all higher than those in root, and Cd and Pb concentrations
      in shoot increased from lower to upper parts, reaching the highest in leaves.
      Significant increases were found in toxic metal concentration in different parts
      of mulberry with increasing EDTA concentration, especially when combined with
      (NH(4))(2)SO(4). Mulberry exhibited high ability to accumulate Cd with
      bioconcentration factors (BCFs) higher than 1. EDTA application also
      significantly increased Cd BCFs. More than 30 % of metal uptake was concentrated
      in mulberry branches (stem of above 100 cm height) and leaves. Results presented
      here show that mulberry is a woody plant that has the potential of Cd
      phytoextraction from MSW compost by removing leaves and cutting branches. The
      application of EDTA combined with (NH(4))(2)SO(4) significantly enhanced the
      efficiency of mulberry in removing Cd from the compost medium. Adding
      (NH(4))(2)SO(4) into the compost will lower the risk of the exposure of
      environment to excessive non-biodegradable EDTA in a large-scale EDTA-assisted
      phytoextraction by reducing the dosage of EDTA. In China, the need for sod is
      increasing day by day. Sod is often produced on arable soil and sold together
      with soils. This would lead to the soil being infertile and the soil layer thin.
      After several times' production, the soil can no longer be used for cultivating
      crops and be destroyed. In order to fully utilize MSW compost resources and save
      valuable soil resources, MSW compost can be used to replace arable soil to
      produce sod after extraction of toxic metals in it.

PMID- 22661281
TI  - Capture of kinesthesis by a competing cutaneous input.
AB  - In four experiments, blindfolded participants were presented with pairs of
      stimuli simultaneously, one to each index finger. Participants moved one index
      finger, which was presented with cutaneous and/or kinesthetic stimuli, and this
      movement caused a raised line to move underneath the other, stationary index
      finger in a yoked manner. The stimuli were 180o rotations of each other (e.g., <
      and >), and thus when a < was traced with the moving finger, it caused a > to be
      felt at the stationary finger. When asked to report the experience, participants
      predominantly reported the cutaneous stimulus, seemingly being ignorant of the
      kinesthetic stimulus. This appears to be an intrahaptic capture phenomenon, which
      is of interest because it suggests that conflict between intrahaptic sensory
      stimuli can go unnoticed; sometimes we are unaware of how we moved, and sometimes
      we do not know what we touched. The results are interpreted in light of optimal
      integration, perceptual suppression, reafference suppression, and inattentional
      blindness.

PMID- 22661280
TI  - Genome-wide genetic associations with IFNgamma response to smallpox vaccine.
AB  - Smallpox is a deadly and debilitating disease that killed hundreds of millions of
      people in the past century alone. The use of Vaccinia virus-based smallpox
      vaccines led to the eradication of smallpox. These vaccines are remarkably
      effective, inducing the characteristic pustule or "take" at the vaccine site in
      >97 % of recipients, and inducing a wide spectrum of long-lasting humoral and
      cellular immune responses. The mechanisms behind inter-individual vaccine
      response variability are likely to involve host genetic variation, but have not
      been fully characterized. We report here the first smallpox vaccine response
      genome-wide association study of over 1,000 recent recipients of Dryvax((r)). The
      data presented here focus on cellular immune responses as measured by both
      production of secreted IFNgamma and quantitation of IFNgamma secreting cells by
      ELISPOT assay. We identified multiple significant SNP associations in genes
      (RASA1, ADRA1D, TCF7L1, FAS) that are critical components of signaling pathways
      that directly control lymphocyte IFNgamma production or cytotoxic T cell
      function. Similarly, we found many associations with SNPs located in genes
      integral to nerve cell function; findings that, given the complex interplay
      between the nervous and immune systems, deserve closer examination in follow-up
      studies.

PMID- 22661282
TI  - Clinical role of a modified seton technique for the treatment of trans
      sphincteric and supra-sphincteric anal fistulas.
AB  - PURPOSES: We have devised a modified seton technique that resects the external
      fistula tract while preserving the anal sphincter muscle. This study assessed the
      technique when used for the management of complex anal fistulas. METHODS: Between
      January 2006 and December 2007, 239 patients (208 males and 31 females, median
      age: 41 years) underwent surgery for complex anal fistulas using the technique.
      Of the 239 patients, 198 patients had trans-sphincteric fistula and 41 patients
      had supra-sphincteric fistula. RESULTS: The durations of the surgeries were 17
      min (47, 13) [median (range, interquartile range)] for trans-sphincteric fistulas
      and 38 (44, 16) for supra-sphincteric fistulas. The durations of the surgeries
      were significantly (P < 0.05) longer for supra-sphincteric fistula than trans
      sphincteric fistula. The hospital stays were 4 (13, 2) days and 5 (14, 3) days,
      respectively, for trans- and supra-sphincteric fistulas. The durations of seton
      placement until the spontaneous dropping of the seton were 42 (121, 48) and 141
      (171, 55) days respectively. The recurrence rate was 0 % in patients with trans
      sphincteric fistulas and 4.9 % (2 of 41) in patients with supra-sphincteric
      fistulas (P < 0.01). Serious incontinence was not observed. CONCLUSIONS: The
      technique provided favorable results for the treatment of complex anal fistulas
      and could be safely applied while preserving the sphincter function and
      conserving fecal continence.

PMID- 22661283
TI  - Concomitant aortic valve and ascending aorta replacement with moderate
      hypothermic circulatory arrest to treat an aortic bicuspid valve with post
      stenotic dilatation.
AB  - We recommend concomitant surgery for aortic valve replacement (AVR) and ascending
      aortic replacement using moderate hypothermic circulatory arrest (CA) for post
      stenotic dilatation complicated by an aortic bicuspid valve. Cardiopulmonary
      bypass (CPB) was established from the right atrium to the dilated ascending
      aorta. As soon as the rectal temperature decreased to 28  degrees C, CA was
      commenced and the open distal anastomosis of a polyester prosthesis, without any
      cerebral perfusion, was completed. AVR was then carried out during rapid re
      warming with CPB using a side arm of the prosthesis. This procedure exhibited
      safe and satisfactory results. There are many benefits of carrying out the
      procedure in this way; it avoids the requirement for cannulation to a calcified
      aortic arch, provides a good operative field, for an easier distal anastomosis
      and suturing at the valve site, and reduces the risk of further dilatation or
      dissection of the residual ascending aorta in the later phase.

PMID- 22661284
TI  - Water-soluble rice bran enzymatic extract attenuates dyslipidemia, hypertension
      and insulin resistance in obese Zucker rats.
AB  - BACKGROUND AND PURPOSE: Rice bran enzymatic extract (RBEE) has advantages
      compared to the original rice bran or its oils including water solubility, lack
      of rancidity and increased content in high nutritional proteins and nutraceutical
      compounds, particularly phytosterols, gamma-oryzanol and tocols. Our aim was to
      determine the beneficial effects of RBEE in the pathogenesis of metabolic
      syndrome in obese Zucker rats. METHODS: Obese Zucker rats and their lean
      littermates were fed a 1 and 5 % RBEE-supplemented diet (O1, O5, L1 and L5).
      Simultaneously, obese and lean Zucker rats, fed a standard diet, were used as
      controls (OC and LC, respectively). Body weight, food and water intake, and
      systolic blood pressure were weekly evaluated. After treatment, biochemical
      assays of serum glucose, insulin, triglycerides (TG), total cholesterol (TC), non
      esterified fatty acids (NEFA), adiponectin and nitrates (NO((x))) were
      determined. RESULTS: RBEE treatment reduced circulating levels of TG and TC,
      whereas increased HDL-cholesterol without altering NEFA values in obese rats. The
      extract also induced a significant dose-dependent reduction of hypertension
      linked to obesity. RBEE of 5 % improved insulin resistance and subsequently
      reduced HOMA-IR index without altering serum glucose levels. Obese animals
      treated with RBEE showed partial restoration of adiponectin levels and a
      significant attenuation of pro-inflammatory values of NO((x)). CONCLUSION: These
      findings evidence the nutraceutical properties of RBEE against the pathogenesis
      of metabolic syndrome by attenuating dyslipidemia, hypertension and insulin
      resistance as well as by restoring hypoadiponectinemia associated to obesity.

PMID- 22661285
TI  - Tyrphostin AG490 agent modestly but significantly prevents onset of type 1 in NOD
      mouse; implication of immunologic and metabolic effects of a Jak-Stat pathway
      inhibitor.
AB  - Previously, we have reported that the Jak-Stat signaling pathway is defective in
      NOD mice. In this study, prediabetic female NOD mice (4 weeks) were treated by
      intraperitoneal injection either with AG490 or DMSO three times per week for 4
      consecutive weeks, followed by once a week for an additional 6 weeks. The onset
      of diabetes was attenuated in NOD mice treated with AG490 relative to DMSO
      treated control mice (p < 0.02). From an immunological standpoint, AG490 induced
      the expression of Foxp3 in CD4(+)CD25(-) T-cells and down-regulated expression of
      co-stimulatory molecules in dendritic cells (DC) both in vitro and in vivo. AG490
      treated CD4+CD25- T-cells and DC in vitro, acquired regulatory functions; namely,
      the ability to suppress proliferation of a responding cell population in vitro.
      AG490 treatment resulted in significant reduction of blood glucose values and
      increased expression of PPARgamma in splenocytes and markedly increased
      expression PPARgamma2 but not PPARgamma1 in adipocyte in vitro. Presence of
      multiple Stat5 DNA binding consensus sequences within the promoter region of the
      PPARgamma gene in human and in mouse suggests that PPARgamma is downstream to the
      Jak-Stat signaling pathway. This study highlights a critical role of the Jak-Stat
      signaling pathway in the pathogenesis of T1D and suggests that blocking the Jak
      Stat signaling pathway by AG490 as a tyrosine kinase inhibitor may provide an
      effective means for preventing autoimmune T1D via both immunological and
      metabolic effects.

PMID- 22661287
TI  - Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase,
      in patients with advanced solid tumors.
AB  - The purpose of this study was to determine the maximum-tolerated dose (MTD),
      pharmacokinetics and safety profile for two different dosing regimens of
      barasertib, a selective inhibitor of Aurora B Kinase. In this Phase I trial,
      patients with advanced solid malignancies were treated with escalating doses of
      barasertib, administered as either a 48-h continuous infusion or as two 2-h
      infusions on consecutive days, both every 14 days of a 28-day cycle. Thirty-five
      patients were treated. The MTDs were 150 mg as a 48-h continuous infusion and 220
      mg administered as two 2-h infusions (110 mg/day, days 1, 2, 15 and 16), with
      neutropenia the dose-limiting toxicity (DLT) of each schedule. Common Terminology
      Criteria of Adverse Events (CTCAE) grade >= 3 neutropenia (with or without fever)
      occurred in 34% of patients overall. Other adverse events, many of hematologic or
      gastrointestinal etiology, were of mild or moderate intensity. No objective tumor
      responses were observed, although stable disease was observed in 23% of patients.
      Systemic exposure to barasertib-hQPA, the more active moiety to which barasertib
      is converted, was observed by 1 and 6 h into the 2-h and continuous infusion,
      respectively, and exhibited linear pharmacokinetics. In summary, barasertib was
      generally well tolerated, with neutropenia the most frequent and dose-limiting
      toxicity, irrespective of schedule. Future development of barasertib will depend
      on better definition of its therapeutic index.

PMID- 22661288
TI  - Inhibition of cancer growth and induction of apoptosis by BGP-13 and BGP-15, new
      calcipotriene-derived vitamin D3 analogs, in-vitro and in-vivo studies.
AB  - One of the most innovative approaches to the treatment of cancer entails the use
      of 1alpha,25-dihydroxyvitamin D3 (calcitriol) analogs to inhibit cancer cell
      growth. We demonstrate here that BGP-13, a new calcipotriene-based 1alpha,25
      dihydroxyvitamin D3 analog that we synthesized in our laboratory, inhibits the
      growth of prostate cancer (LNCaP), breast cancer (MCF-7), and colon cancer (HT
      29) cell lines. Moreover, we also show that BGP-13 causes cells both to
      accumulate in G0-G1 and to activate caspase-3 and undergo apoptosis. In addition,
      we observed elevated vitamin D receptor (VDR) mRNA and protein levels in both
      LNCaP and MCF-7 cells following the exposure of the two cell lines to BGP-13.
      Importantly, we found that both the new analog BGP-13 and also BGP-15, another
      calcipotriene-based analog we synthesized previously and about which we published
      recently, inhibit the growth of HT-29 tumor xenografts in nude mice.

PMID- 22661289
TI  - A fluorescent assay for ceramide synthase activity.
AB  - The sphingolipids are a diverse family of lipids with important roles in membrane
      compartmentalization, intracellular signaling, and cell-cell recognition. The
      central sphingolipid metabolite is ceramide, formed by the transfer of a variable
      length fatty acid from coenzyme A to a sphingoid base, generally sphingosine or
      dihydrosphingosine (sphinganine) in mammals. This reaction is catalyzed by a
      family of six ceramide synthases (CerS1-6). CerS activity is usually assayed
      using either radioactive substrates or LC-MS/MS. We describe a CerS assay with
      fluorescent, NBD-labeled sphinganine as substrate. The assay is readily able to
      detect endogenous CerS activity when using amounts of cell or tissue homogenate
      protein that are lower than those reported for the radioactive assay, and the
      Michaelis-Menten constant was essentially the same for NBD-sphinganine and
      unlabeled sphinganine, indicating that NBD-sphinganine is a good substrate for
      these enzymes. Using our assay, we confirm that the new clinical
      immunosuppressant FTY720 is a competitive inhibitor of CerS activity, and show
      that inhibition requires the compound's lipid tail and amine headgroup. In
      summary, we describe a fluorescent assay for CerS activity that circumvents the
      need to use radioactive substrates, while being more accessible and cheaper than
      LC-MS based assays.

PMID- 22661290
TI  - Psychotic aura symptoms in familial hemiplegic migraine type 2 (ATP1A2).
AB  - INTRODUCTION: Neuropsychological symptoms are rare in familial hemiplegic
      migraine (FHM). There are no reports of psychotic symptoms in FHM type 2
      (ATP1A2). We examined a family with a FHM phenotype due to a M731T mutation in
      ATP1A2. A 10-year follow-up allowed us to observe complex auras, including
      psychotic symptoms in two siblings. CASE REPORT: Male, 48 years old, with an aura
      that included complex illusions with a feeling of time travelling, coincident
      with other aura features. The aura was regarded as mystical by the patient.
      Female, 38 years old, with a complex migraine aura, during which she believed she
      had the ability to time travel and was being followed by lobbyists who wanted to
      steal this ability from her. DISCUSSION: FHM type 2 must be included in the list
      of differential diagnoses of acute psychosis in patients with a previous history
      of migraine aura.

PMID- 22661291
TI  - Recent advances in the management of difficult constipation.
AB  - Constipation is a highly prevalent disorder. Some patients suffer from acute,
      intermittent episodes of constipation. Others, however, suffer from chronic
      constipation, a term that refers to those patients with symptoms of constipation
      for more than 6 months. In clinical practice, chronic constipation is often used
      interchangeably with the term functional constipation, which is currently defined
      using the Rome III criteria. Symptoms can be burdensome, leading to a reduction
      in patients' quality of life. In addition, chronic constipation is important
      because it imposes a significant economic impact to the health care system. Some
      patients with chronic constipation have persistent symptoms despite implementing
      lifestyle changes and using either over-the-counter agents or prescription
      medications. These patients may be categorized as having difficult constipation.
      This report will focus on recent advances in the management of difficult
      constipation, and include a discussion of new and upcoming medications as well as
      new diagnostic tests and procedures.

PMID- 22661292
TI  - Neurologic complications of bariatric surgery: involvement of central,
      peripheral, and enteric nervous systems.
AB  - Approximately one in three Americans is obese. Current society guidelines
      recommend bariatric surgery after conservative measures at weight loss have
      failed. The frequency of bariatric surgeries has increased significantly over the
      past decade. While considered both safe and effective, bariatric surgery presents
      a distinct set of risks. This review focuses on the neurological complications of
      bariatric surgery. Injuries have been reported at all levels of the nervous
      system, including the central, peripheral, and enteric nervous system. Injury can
      be classified according to time of presentation and location. The two main
      mechanisms of nerve injury are from mechanical injury or as a consequence of
      malnutrition. Encephalopathy, peripheral neuropathies, myelopathies, and
      radiculoneuropathies have all been reported. Mechanical injuries likely occur
      from mechanical compression. Malnutrition injuries result from multi
      micronutrient deficiencies. The most likely candidates are vitamin B12, folate,
      zinc, thiamin, copper, vitamin A, and vitamin E deficiencies.

PMID- 22661294
TI  - Court dwarfs: an overview of European paintings from fifteenth to eighteenth
      century.
AB  - Since antique times, dwarfs have been commonly employed at court, mostly as
      servants, entertainers, or personal attendants upon noble women and noblemen.
      Their presence at European Renaissance courts was very common, as demonstrated by
      their presence alongside to their masters or mistress in several artworks of that
      period. Aim of our paper is to derive clinical information regarding the type of
      dwarfism affecting people living and acting at European courts from an overview
      of paintings dating fifteenth to the eighteenth century.

PMID- 22661293
TI  - Emerging concepts about prenatal genesis, aberrant metabolism and treatment
      paradigms in polycystic ovary syndrome.
AB  - The interactive nature of the 8th Annual Meeting of the Androgen Excess and PCOS
      Society Annual Meeting in Munich, Germany (AEPCOS 2010) and subsequent exchanges
      between speakers led to emerging concepts in PCOS regarding its genesis,
      metabolic dysfunction, and clinical treatment of inflammation, metabolic
      dysfunction, anovulation and hirsutism. Transition of care in congenital adrenal
      hyperplasia from pediatric to adult providers emerged as a potential model for
      care transition involving PCOS adolescents.

PMID- 22661296
TI  - The effect of centralization of caseload for primary brain tumor surgeries:
      trends from 2001-2007.
AB  - BACKGROUND: Improved patient outcomes have been associated with high-caseload
      hospitals for a multitude of conditions. This study analyzed adult patients
      undergoing surgical resection or biopsy of primary brain tumors. The aim of this
      study is two-fold: (1) to evaluate whether the trend towards centralization of
      primary brain tumor care in the US has continued during the period of between
      2001 and 2007, and (2) to analyze volume-outcome effects. METHODS: Surgical
      volume trends of adults undergoing resection/biopsy of primary supratentorial
      brain tumors were analyzed using the Nationwide Inpatient Sample. High- and low
      caseload hospitals were defined as those performing in the highest and lowest
      quintile of procedures, respectively. Length of stay (LOS), mortality and
      discharge disposition were the main outcomes of interest. RESULTS: NIS estimated
      124,171 patients underwent resection/biopsy of primary supratentorial brain
      tumors between 2001 and 2007 in the US. The average number of annual resections
      in the highest 2 % and lowest 25 % caseload hospitals were 322 and 12 cases,
      respectively. Surgeries in high-caseload hospitals increased by 137 %, while
      those in low-caseload centers declined by 16.0 %. Overall, mortality decreased 35
      %, with a reduction of 45 % in high- (from 2.2 % to 1.2 %) and 19 % in low- (from
      3.2 % to 2.6 %) caseload hospitals. High-caseload centers had lower LOS than
      hospitals with lower caseload centers (6.4 vs. 8.0 days, p < 0.001). Multivariate
      analysis showed that patients treated in low-volume hospitals had an increased
      risk of death (OR 1.8, CI: 1.2-2.7, p = 0.006) and adverse discharge (OR 1.4, CI:
      1.1-1.7, p = 0.01). CONCLUSIONS: Neurosurgical caseload at the nation's high
      volume craniotomy centers has continued to rise disproportionately, while low
      caseload centers have seen a decrease in overall surgical volume. Over the time
      period between 2001 and 2007 there was a trend towards improved in-hospital
      mortality, LOS and discharge disposition for all hospitals; however, the trend is
      convincingly favorable for high-caseload hospitals.

PMID- 22661295
TI  - Promoter variants in the MSMB gene associated with prostate cancer regulate
      MSMB/NCOA4 fusion transcripts.
AB  - Beta-microseminoprotein (MSP)/MSMB is an immunoglobulin superfamily protein
      synthesized by prostate epithelial cells and secreted into seminal plasma.
      Variants in the promoter of the MSMB gene have been associated with the risk of
      prostate cancer (PCa) in several independent genome-wide association studies.
      Both MSMB and an adjacent gene, NCOA4, are subjected to transcriptional control
      via androgen response elements. The gene product of NCOA4 interacts directly with
      the androgen receptor as a co-activator to enhance AR transcriptional activity.
      Here, we provide evidence for the expression of full-length MSMB-NCOA4 fusion
      transcripts regulated by the MSMB promoter. The predominant MSMB-NCOA4 transcript
      arises by fusion of the 5'UTR and exons 1-2 of the MSMB pre-mRNA, with exons 2-10
      of the NCOA4 pre-mRNA, producing a stable fusion protein, comprising the
      essential domains of NCOA4. Analysis of the splice sites of this transcript shows
      an unusually strong splice acceptor at NCOA4 exon 2 and the presence of Alu
      repeats flanking the exons potentially involved in the splicing event.
      Transfection experiments using deletion clones of the promoter coupled with
      luciferase reporter assays define a core MSMB promoter element located between 
      27 and -236 of the gene, and a negative regulatory element immediately upstream
      of the start codon. Computational network analysis reveals that the MSMB gene is
      functionally connected to NCOA4 and the androgen receptor signaling pathway. The
      data provide an example of how GWAS-associated variants may have multiple genetic
      and epigenetic effects.

PMID- 22661297
TI  - Lower proportion of naive peripheral CD8+ T cells and an unopposed pro
      inflammatory response to human Cytomegalovirus proteins in vitro are associated
      with longer survival in very elderly people.
AB  - The low percentages of naive T cells commonly observed in elderly people are
      thought to be causally associated with mortality, primarily from infectious
      disease, and are taken as a hallmark of "immunosenescence". Whether low levels of
      naive cells actually do associate with mortality has, however, not been tested in
      longitudinal studies. Here, we present correlations between peripheral T-cell
      phenotypes and 8-year survival in individuals from the population-based
      prospective Leiden 85-plus Study. Counter-intuitively, we found that a lower
      frequency of naive CD8+ T cells (characterized as CD45RA+CCR7+CD27+CD28+) at
      baseline (>88 years) correlated with significantly better survival, while there
      was a tendency for the reciprocal accumulation of late-differentiated effector
      memory cells (CD45RA-CCR7-CD27-CD28-) also to associate with better survival.
      These findings suggest that better retention of memory cells specific for
      previously encountered antigens may provide a survival advantage in this
      particular population. Given the prevalence of Cytomegalovirus (CMV) and its
      reported association with immunosenescence, we tested whether memory for this
      potential pathogen was relevant to survival. We found that individuals mounting
      an exclusively pro-inflammatory ex vivo response (TNF, IFN-gamma, IL-17) to the
      major CMV target molecules pp65 and IE1 had a significant survival advantage over
      those also having anti-inflammatory responses (IL-10). These findings suggest
      that higher levels of naive T cells may not necessarily be associated with a
      survival advantage and imply that the nature of immunosurveillance against CMV
      may be crucial for remaining longevity, at least in the very elderly. 

PMID- 22661298
TI  - Age-related changes in cutaneous sensation in the healthy human hand.
AB  - Cutaneous sensation deteriorates with age. It is not known if this change is
      consistent over the entire hand or if sensation is affected by changes in skin
      mechanics. Cutaneous perceptual thresholds were tested at eight sites in the
      glabrous skin and two in the hairy skin of both hands in 70 subjects (20-88
      years), five male and five female per decade, using calibrated von Frey
      filaments, two-point discrimination, and texture discrimination. Venous occlusion
      at the wrist (40 +/- 10 mmHg) and moisturizer were used to alter skin mechanics.
      Cutaneous thresholds increased significantly with age (p < 0.001); von Frey
      thresholds were 0.04 g [0.02-0.07] (median and interquartile range) in the 20s
      and 0.16 g [0.04-0.4] in the 80s, with differences between hands for older
      females (p = 0.044) but not males. The pattern of changes in cutaneous sensation
      varied according to the site tested with smaller changes on the fingers compared
      to the palm. Two-point discrimination deteriorated with age (p = 0.046), but with
      no interaction between sex, handedness, or changes in skin mechanics. There were
      no significant differences for texture discrimination. Changes in skin mechanics
      improved cutaneous thresholds in the oldest males after moisturizing (p = 0.001)
      but not otherwise. These results emphasize the complex pattern of age-related
      deterioration in cutaneous sensation with differences between sexes, the hands,
      sites on the hand, and the mode of testing. As the index fingertip is not a
      sensitive indicator of sensory decline, the minimum assessment of age-related
      changes in cutaneous sensation should include both hands, and sites on the palm.

PMID- 22661299
TI  - Chronic caloric restriction partially protects against age-related alteration in
      serum metabolome.
AB  - Calorie restriction (CR) remains the most robust metabolic intervention to extend
      lifespan and improve healthspan in several species. Using global and targeted
      mass spectrometry-based metabolomics approaches, here we show that chronic CR
      prevents age-related changes in specific metabolic signatures. Global metabolomic
      analysis using ultra-performance liquid chromatography-tandem mass spectrometry
      detected more than 7,000 metabolites in sera from ad-libitum-fed young, aged, and
      aged C57BL/6 mice maintained on 40 % CR. Multivariate statistical analysis of
      mass spectrometry data revealed a clear separation among the young, aged, and
      aged-CR mice demonstrating the potential of this approach for producing reliable
      metabolic profiles that discriminate based on age and diet. We have identified
      168 discriminating features with high statistical significance (p <= 0.001) and
      validated and quantified three of these metabolites using targeted metabolite
      analysis. Calorie restriction prevented the age-related alteration in specific
      metabolites, namely lysophosphatidylcholines (16:1 and 18:4), sphingomyelin
      (d18:1/12:0), tetracosahexaenoic acid, and 7alpha-dihydroxy-4-cholesten-3-one, in
      the serum. Pathway analysis revealed that CR impacted the age-related changes in
      metabolic byproducts of lipid metabolism, fatty acid metabolism, and bile acid
      biosynthesis. Our data suggest that metabolomics approach has the potential to
      elucidate the metabolic mechanism of CR's potential anti-aging effects in larger
      scale investigations.

PMID- 22661300
TI  - The benefits of preparing data for sharing even when you don't.

PMID- 22661301
TI  - Meditation over medication for irritable bowel syndrome? On exercise and
      alternative treatments for irritable bowel syndrome.
AB  - Complimentary alternative treatment regimens are widely used in irritable bowel
      syndrome (IBS), but the evidence supporting their use varies. For psychological
      treatment options, such as cognitive behavioral therapy, mindfulness, gut
      directed hypnotherapy, and psychodynamic therapy, the evidence supporting their
      use in IBS patients is strong, but the availability limits their use in clinical
      practice. Dietary interventions are commonly included in the management of IBS
      patients, but these are primarily based on studies assessing physiological
      function in relation to dietary components, and to a lesser degree upon research
      examining the role of dietary components in the therapeutic management of IBS.
      Several probiotic products improve a range of symptoms in IBS patients. Physical
      activity is of benefit for health in general and recent data implicates its
      usefulness also for IBS patients. Acupuncture does not seem to have an effect
      beyond placebo in IBS. A beneficial effect of some herbal treatments has been
      reported.

PMID- 22661302
TI  - Polygyny, partnership concurrency, and HIV transmission in Sub-Saharan Africa.
AB  - We study the relationship between polygyny and HIV infection using nationally
      representative survey data with linked serostatus information from 20 African
      countries. Our results indicate that junior wives in polygynous unions are more
      likely to be HIV positive than spouses of monogamous men, but also that HIV
      prevalence is lower in populations with more polygyny. With these results in
      mind, we investigate four explanations for the contrasting individual- and
      ecological-level associations. These relate to (1) the adverse selection of HIV
      positive women into polygynous unions, (2) the sexual network structure
      characteristic of polygyny, (3) the relatively low coital frequency in conjugal
      dyads of polygynous marriages (coital dilution), and (4) the restricted access to
      sexual partners for younger men in populations where polygynous men presumably
      monopolize the women in their community (monopolizing polygynists). We find
      evidence for some of these mechanisms, and together they support the proposition
      that polygynous marriage systems impede the spread of HIV. We relate these
      results to the debate about partnership concurrency as a primary behavioral
      driver for the fast propagation of HIV in some parts of sub-Saharan Africa.

PMID- 22661303
TI  - Mortality from the influenza pandemic of 1918-1919: the case of India.
AB  - Estimates of worldwide mortality from the influenza pandemic of 1918-1919 vary
      widely, from 15 million to 100 million. In terms of loss of life, India was the
      focal point of this profound demographic event. In this article, we calculate
      mortality from the influenza pandemic in India using panel data models and data
      from the Census of India. The new estimates suggest that for the districts
      included in the sample, mortality was at most 13.88 million, compared with 17.21
      million when calculated using the assumptions of Davis (1951). We conclude that
      Davis' influential estimate of mortality from influenza in British India is
      overstated by at least 24%. Future analyses of the effects of the pandemic on
      demographic change in India and worldwide will need to account for this
      significant downward revision.

PMID- 22661304
TI  - Mouse models of otitis media: strengths and limitations.
AB  - There has been a rapid rise in the use of the mouse to investigate pathobiology
      of otitis media. This is for good reason, including easy husbandry, but also
      capacity for genetic manipulation of the mouse. Insights into human disease have
      been gleaned from mouse models, but there are limitations of the mouse-to-man
      approach. First, important differences exist between mouse and man, particularly
      in immune function. Second, functional equivalence of genes in the 2 species is
      not ensured. Third, laboratory mice of a uniform genetic background and
      environment are an inadequate model of the plethora of factors affecting complex
      disease in humans. Finally, gene function in mouse models is often obliterated
      using gene knockout technology, but this is a poor mimic of normal gene variation
      in man. These drawbacks of the mouse may in the future limit its usefulness in
      otitis media research.

PMID- 22661306
TI  - Attenuation of the jasmonate burst, plant defensive traits, and resistance to
      specialist monarch caterpillars on shaded common milkweed (Asclepias syriaca).
AB  - Plant responses to herbivory and light competition are often in opposing
      directions, posing a potential conflict for plants experiencing both stresses.
      For sun-adapted species, growing in shade typically makes plants more
      constitutively susceptible to herbivores via reduced structural and chemical
      resistance traits. Nonetheless, the impact of light environment on induced
      resistance has been less well-studied, especially in field experiments that link
      physiological mechanisms to ecological outcomes. Accordingly, we studied induced
      resistance of common milkweed (Asclepias syriaca, a sun-adapted plant), and
      linked hormonal responses, resistance traits, and performance of specialist
      monarch caterpillars (Danaus plexippus) in varying light environments. In natural
      populations, plants growing under forest-edge shade showed reduced levels of
      resistance traits (lower leaf toughness, cardenolides, and trichomes) and
      enhanced light-capture traits (higher specific leaf area, larger leaves, and
      lower carbon-to-nitrogen ratio) compared to paired plants in full sun. In a field
      experiment repeated over two years, only milkweeds growing in full sun exhibited
      induced resistance to monarchs, whereas plants growing in shade were
      constitutively more susceptible and did not induce resistance. In a more
      controlled field experiment, plant hormones were higher in the sun (jasmonic
      acid, salicylic acid, abscisic acid, indole acidic acid) and were induced by
      herbivory (jasmonic acid and abscisic acid). In particular, the jasmonate burst
      following herbivory was halved in plants raised in shaded habitats, and this
      correspondingly reduced latex induction (but not cardenolide induction). Thus, we
      provide a mechanistic basis for the attenuation of induced plant resistance in
      low resource environments. Additionally, there appears to be specificity in these
      interactions, with light-mediated impacts on jasmonate-induction being stronger
      for latex exudation than cardenolides.

PMID- 22661307
TI  - Mosaic eucalypt trees suggest genetic control at a point that influences several
      metabolic pathways.
AB  - Mosaic trees contain more than one phenotype. The two Eucalyptus mosaic trees
      studied here (E. melliodora and E. sideroxylon) are predominantly susceptible to
      insect herbivory, with the leaves on a single large branch on each tree resisting
      herbivory. We used gas chromatography-mass spectrometry and high-pressure liquid
      chromatography to analyze the chemical profile of leaves of the mosaic trees, as
      well as leaves of adjacent non-mosaic con-specifics. We show that the leaves of
      the two phenotypes are distinctly different. Compared to the susceptible (S)
      leaves on the same tree, the resistant (R) leaves on the mosaic trees had low
      concentrations of sesquiterpenes (E. melliodora: 2 vs. 24 mg.g(-1) dry matter; E.
      sideroxylon: 8 vs. 22 mg.g(-1) dry matter), high concentrations of FPCs (E.
      melliodora: 5.4 vs. 0.3 mg.g(-1) dry matter; E. sideroxylon: 9.8 vs. 0.2 mg.g(-1)
      dry matter) but similar concentrations of nitrogen (E. melliodora: 15.4 vs. 16.8
      mg.g(-1) dry matter; E. sideroxylon: 13.1 vs. 14.0 mg.g(-1) dry matter). The only
      difference between the two mosaic trees was in the levels of monoterpenes. The R
      leaves from the mosaic E. melliodora contained higher concentrations of
      monoterpenes compared to the S leaves (12 vs. 6 mg.g(-1) dry matter). In
      contrast, the leaves from the E. sideroxylon mosaic contained much higher
      concentrations of monoterpenes with a reversed pattern (R: 26 vs. S: 45 mg.g(-1)
      dry matter). There were qualitative differences too on the mosaic trees. The R
      leaves of both species contained much higher concentrations of the monoterpene,
      1,8-cineole, whereas the S chemotype of E. sideroxylon only had high
      concentrations of phellandrenes. Furthermore, the chemical differences between
      leaves on the R and S branches of the mosaic trees resembled those between the
      leaves of R and S con-specific trees in the same population. We use these data
      and knowledge of secondary metabolite biosynthesis to propose that high-level
      transcriptional differences may control the profile of specialized metabolites in
      eucalypts.

PMID- 22661305
TI  - Investigational agents in development for the treatment of ovarian cancer.
AB  - Although significant success has been achieved in the treatment of advanced and
      recurrent ovarian cancer, there is clearly room for improvement. The use of
      targeted agents in this patient population has the promise to provide improved
      survival and quality of life. There are a myriad of relevant pathways under
      exploration in all settings of ovarian cancer. Clinical trial data are
      accumulating for antiangiogenic therapy, including vascular endothelial growth
      factor (VEGF)-specific inhibitors and multiple angiogenic signaling target
      inhibitors, as well as poly-ADP-ribose polymerase (PARP) inhibitors. Other types
      of tumorigenic pathway inhibitors, including those that target
      phosphatidylinositol-3-kinase (PI3K), mammalian target of rapamycin (mTOR),
      protein kinase B (AKT), Src, folate receptor alpha, and insulin-like growth
      factor-1 receptor (IGF-1R) pathways are in earlier phases of development for
      ovarian cancer. Attempts to target the epidermal growth factor receptor (EGFR) of
      ovarian tumors have been met with limited success; however, newer agents that
      inhibit this pathway show promise. Finally, with recognition of the role of Wee-1
      in p53-deficient tumors, an inhibitor of this tyrosine kinase is being evaluated
      in recurrent ovarian cancer. The logistical challenge is to determine the optimal
      timing and proper combinations of novel agents independently as well as
      concomitantly with conventional chemotherapeutics. Reported results have been
      modest; however, our growing understanding of these pathways will be potentially
      reflected in greater impact on response and survival.

PMID- 22661309
TI  - High fat-induced obesity associated with insulin-resistance increases FGF-2
      content and causes stromal hyperplasia in rat ventral prostate.
AB  - Obesity affects sex hormone secretion, which can negatively influence prostatic
      structure, homeostasis, and disease. This investigation aimed to evaluate the
      repercussions of obesity induced by a high-fat diet on the rat prostate, with or
      without treatment with the aromatase inhibitor, Letrozole. Adult Wistar rats were
      fed a high-fat diet (20% saturated fat, O) for 15 weeks to induce obesity or
      received a balanced diet (4% fat, C). Then, a group of C and O rats were daily
      treated with Letrozole (1 mg/kg b.w. per day) for 2 weeks (CL and OL,
      respectively). Subsequently, ventral prostate was processed for analysis by
      transmission electron microscopy, immunohistochemistry, and Western blotting.
      Obesity decreased 70% of the testosterone plasma level. The prostate showed
      epithelial atrophy and dilated acini in the intermediate portion and epithelial
      wrinkling in the distal tips. The relative frequency of smooth muscle alpha-actin
      in the O group increased by 67%. Ultrastructurally, epithelial cells in obese
      animals presented altered secretory organelles, lipid droplets, and thicker
      subjacent fibromuscular layer. Letrozole treatment caused a partial restoration
      of the prostatic changes caused by obesity. Obesity increased the prostatic
      content of fibroblast growth factor-2 (FGF-2) by 150%, and Letrozole treatment
      increased this protein even more in the control and obese groups. This
      investigation shows that obesity provokes structural and ultrastructural changes
      in the epithelium of rat prostate; these changes might affect gland homeostasis
      and physiology. The epithelial and smooth muscle cell hyperplasia and increased
      FGF-2 expression observed in this experimental model of obesity/insulin
      resistance might explain the high frequency of benign prostatic hyperplasia in
      insulin-resistant men.

PMID- 22661308
TI  - Opposing roles of cell death-inducing DFF45-like effector B and perilipin 2 in
      controlling hepatic VLDL lipidation.
AB  - Regulation of hepatic very low density lipoprotein (VLDL) assembly and maturation
      is crucial in controlling lipid homeostasis and in the development of metabolic
      disorders, including obesity, hepatic steatosis, and insulin resistance. Cideb, a
      member of cell death-inducing DFF45-like effector (CIDE) protein family, has been
      previously shown to promote VLDL lipidation and maturation. However, the precise
      subcellular location of Cideb-mediated VLDL lipidation and the factors modulating
      its activity remain elusive. In addition to its localization to endoplasmic
      reticulum (ER) and lipid droplets (LD), we observed that Cideb was also localized
      to the Golgi apparatus. Mature and lipid-rich VLDL particles did not accumulate
      in the Golgi apparatus in Cideb(-/-) livers. Interestingly, we observed that
      hepatic perilipin 2/adipose differentiation-related protein (ADRP) levels were
      markedly increased in Cideb(-/-) mice. Liver-specific knockdown of perilipin 2 in
      Cideb(-/-) mice resulted in the reduced accumulation of hepatic triglycerides
      (TAG), increased VLDL-TAG secretion, and the accumulation of mature TAG-rich VLDL
      in the Golgi apparatus. These data reveal that Cideb and perilipin 2 play
      opposing roles in controlling VLDL lipidation and hepatic lipid homeostasis.

PMID- 22661310
TI  - Unusual cause of desynchronization in a cardiac resynchronization device.
AB  - This report describes a new cause of desynchronization encountered in a cardiac
      resynchronization device functioning in the VVIR mode. Left ventricular
      stimulation was inhibited when the sensor-driven rate exceeded the programmed
      left ventricular (LV) maximum trigger rate. With these devices, it is important
      to program the LV maximum trigger interval (essentially equivalent to a LV upper
      interval) to a value equal or faster than the sensor-driven upper rate.

PMID- 22661311
TI  - Testing NF-kappaB-based therapy in hemiparkinsonian monkeys.
AB  - Parkinson's disease (PD) is the most common human neurodegenerative disorder
      affecting movement, balance, flexibility, and coordination. Despite intense
      investigation, no effective therapy is available to stop the onset PD or halt its
      progression. The primate model of PD is considered to be one of the best
      available models for human PD. Since neuroinflammation plays an important role in
      the pathogenesis of PD and NF-kappaB, a proinflammatory transcription factor,
      participates in the transcription of many proinflammatory molecules, this study
      evaluates the ability of a peptide corresponding to the NF-kappaB essential
      modifier (NEMO)-binding domain (NBD) of IkappaB kinase (IKK)alpha or IKKbeta to
      protect dopaminergic neurons in hemiparkinsonian monkeys. First, we found that NF
      kappaB was activated within the substantia nigra pars compacta of 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated hemiparkinsonian monkeys.
      However, intramuscular injection of wild type NBD (wtNBD) peptide reduced nigral
      activation of NF-kappaB and expression of inducible nitric oxide synthase,
      protected both the nigrostriatal axis and neurotransmitters, and improved motor
      functions in hemiparkinsonian monkeys. These findings were specific as mutated
      NBD peptide did not exhibit such effects. These results may help in the
      translation of NF-kappaB-based therapy to PD clinics.

PMID- 22661312
TI  - Necrotizing infundibuloneurohypophysitis: case report and literature review.

PMID- 22661313
TI  - Dorsal and ventral stimuli in cell-material interactions: effect on cell
      morphology.
AB  - Cells behave differently between bidimensional (2D) and tridimensional (3D)
      environments. While most of the in vitro cultures are 2D, most of the in vivo
      extracellular matrices are 3D, which encourages the development of more relevant
      culture conditions, seeking to provide more physiological models for biomedicine
      (e.g., cancer, drug discovery and tissue engineering) and further insights into
      any dimension-dependent biological mechanism. In this study, cells were cultured
      between two protein coated surfaces (sandwich-like culture). Cells used both
      dorsal and ventral receptors to adhere and spread, undergoing morphological
      changes with respect to the 2D control. Combinations of fibronectin and bovine
      serum albumin on the dorsal and ventral sides led to different cell morphologies,
      which were quantified from bright field images by calculating the spreading area
      and circularity. Although the mechanism underlying these differences remains to
      be clarified, excitation of dorsal receptors by anchorage to extracellular
      proteins plays a key role on cell behavior. This approach--sandwich-like culture-
      becomes therefore a versatile method to study cell adhesion in well-defined
      conditions in a quasi 3D environment.

PMID- 22661314
TI  - Short-term and transgenerational effects of the neonicotinoid nitenpyram on
      susceptibility to insecticides in two whitefly species.
AB  - The cosmopolitan silverleaf whitefly, Bemisia tabaci which had coexisted with
      Trialeurodes vaporariorum in Northern China for many years, has become the
      dominant species in the last years. Recent reports show that it is gradually
      displacing the other greenhouse whitefly species. Neonicotinoid, which includes
      nitenpyram, is a major group of insecticides used against whiteflies in various
      crops. When exposed to low doses of insecticides, insects may develop resistance
      by adapting physiologically. The short- and long-term effects of nitenpyram on
      insecticide sensitivity in B. tabaci biotype B and T. vaporariorum adult
      populations have been compared in the present study. After being exposed to
      LC(25) of nitenpyram for 24 h, the B. tabaci biotype B adults showed no
      significant change in susceptibility to nitenpyram or to five other insecticides:
      imidacloprid, acetamiprid, abamectin, chlorpyrifos and beta-cypermethrin. By
      contrast, exposure to the LC(25) of nitenpyram for 24 h led to a significant
      increase in the susceptibility of T. vaporariorum to nitenpyram and imidacloprid,
      by 1.8- and 2-fold, respectively. When exposed for seven generations to the
      LC(25) of nitenpyram, B. tabaci developed 6-fold resistance to nitenpyram, and
      3.1- and 5-fold cross-resistance to imidacloprid and acetamiprid, respectively,
      whereas T. vaporariorum developed lower resistance (3.7-fold) to the nitenpyram
      and very low cross-resistance to imidacloprid (2.5-fold). The higher adaptable
      nature of B. tabaci (demonstrated here in the case of nitenpyram) when exposed to
      low doses of insecticides may provide a selective advantage when competing with
      T. vaporariorum in crops.

PMID- 22661315
TI  - Comparison of remote consequences in Taraxacum officinale seed progeny collected
      in radioactively or chemically contaminated areas.
AB  - We carried out a comparative study of seed progeny taken from the dandelion
      (Taraxacum officinale s.l.) coenopopulations exposed for a long time to
      radioactive or chemical contamination originated from the East-Ural radioactive
      trace zone (EURT) or Nizhniy Tagil metallurgical combine impact zone (NTMC),
      respectively. Coenopopulations from EURT, NTMC and background areas significantly
      differ from each other with respect to the qualitative and quantitative
      composition of allozyme phenes. An analysis of clonal diversity showed the
      uniqueness of all coenopopulations in terms of their phenogenetics. P-generation
      seed viability was found to decrease in a similar manner as all types of the
      industrial stress increased. Studies of F (1)-generation variability in radio-
      and metal resistance by family analysis showed that seed progeny from EURT impact
      zone possessed high viability that, however, was accompanied by development of
      latent injuries resulting in low resistance to additional man-caused impacts. In
      F (1)-generation originated from NTMC zone, high seed viability was combined with
      increased resistance to provocative heavy metal and radiation exposure. No
      significant differences in responses to 'habitual' and 'new' factors, i.e. pre
      adaptation effect, were found in samples from the contaminated areas.

PMID- 22661316
TI  - Fluctuating estuarine conditions are not confounding factors for the Comet assay
      assessment of DNA damage in the mussel Mytilus edulis.
AB  - The Comet assay is finding increasing application as a biomarker assay for the
      genotoxic potential of contaminants in field transplantation experiments
      involving mussels. Especially in estuaries, habitats that are of particular
      concern, environmental variables, such as salinity, can vary significantly.
      Although hinted at in the literature, there is a lack of clarification as to
      whether changes in salinity or emersion-induced hypoxia have the potential to
      alter background DNA damage in mussels, thus masking the extent of potential
      genotoxic effects following exposure to environmental contaminants. The present
      study exposed Mytilus edulis in the laboratory to static salinities (25, 50, 75,
      and 100 %) for 72 h. Mussels were also subjected to simulated tidal cycles,
      including periods of emersion, for 72 h. None of these treatments resulted in a
      significant change in the level of DNA damage expressed as % tail DNA. These
      experiments demonstrate that salinity, within the limits of the concentrations
      tested, and temporary emersion are not confounding factors for Comet assay data
      derived from M. edulis.

PMID- 22661317
TI  - The comparition of biological characteristics and multilineage differentiation of
      bone marrow and adipose derived Mesenchymal stem cells.
AB  - We compared the two sources of adipose and bone marrow-derived mesenchymal stem
      cells (BMSCs and AMSCs ) in multiple differentiation capacity and biological
      characteristics to provide a theoretical basis for stem cells transplantation. We
      isolated bone marrow- and adipose-derived mesenchymal stem cells and compared
      their phenotype,cell doubling time, the secretion of factors and their ability of
      multi-differentiation. We also compared their differences in T lymphocyte
      activation, proliferation and suppression. BMSCs and AMSCs were similar in cell
      phenotype and the differences existed only in the expression of CD106. On the
      proliferation rate, AMSCs were faster than BMSCs (doubling time 28 vs. 39 h). In
      addition, both of these two sources of cells were able to differentiate into
      bone, fat and cartilage that proved their stem cells properties and the number of
      stem cell progenitors (CFU-F) from adipose tissue were 10 times larger than those
      from bone marrow. But AMSCs showed a diminished capacity for suppressing T
      lymphocyte proliferation and activation compared to BMSCs. Cell origin and
      abundance were decisive factors in stem cells applications and, in the same
      volume, with the same premise of AMSCs and BMSCs, adipose tissue is a more
      promising source of stem cells.

PMID- 22661318
TI  - Continuous subcutaneous infusion of lidocaine for persistent hiccup in advanced
      cancer.
AB  - Persistent hiccup can cause anorexia, weight loss, disabling sleep deprivation,
      anxiety, and depression. Therefore, relief of persistent hiccup is important for
      advanced cancer patients and their family. Most reports on this condition are
      case series reports advocating the use of baclofen, haloperidol, gabapentin, and
      midazolam. However, these medications are occasionally ineffective or accompanied
      by intolerable side effects. The sodium channel blocker lidocaine has been shown
      to be effective in treating a variety of disorders thought to involve neuropathic
      mechanisms. Intravenous administration of lidocaine is common but efficacy has
      also been reported for subcutaneous infusion. In advanced cancer patients,
      subcutaneous infusion is easy, advantageous, and accompanied by less discomfort.
      We report a case of severe and sustained hiccup caused by gastric cancer that was
      successfully treated with a continuous subcutaneous infusion of lidocaine (480 mg
      (24 ml)/day) without severe side effects.

PMID- 22661319
TI  - Sunitinib in pancreatic neuroendocrine tumors.
AB  - Sunitinib is an oral multitarget tyrosine kinase inhibitor with potent
      antiangiogenic properties. Preclinical data have demonstrated that pancreatic
      neuroendocrine tumors depend on vascular endothelial growth factor receptors and
      platelet growth factor receptors-signaling pathways for tumor angiogenesis.
      Sunitinib has recently been approved for the treatment of patients with advanced,
      progressive pancreatic neuroendocrine tumors. Sunitinib has demonstrated
      clinically meaningful improvements in progression-free survival in a double
      blinded randomized trial against placebo, setting progression-free survival as a
      valid endpoint for the evaluation of novel agents in patients with pancreatic
      neuroendocrine tumors. Although patients who progressed in this phase III trial
      were allowed to cross-over, a trend toward improvement in overall survival was
      also observed. In this trial, side effects reported with sunitinib were those
      previously reported in other tumor types, including hand-foot syndrome, diarrhea,
      and hypertension. This trial also investigated patient-reported outcome and
      showed that treatment with sunitinib did not affect quality of life of patient.
      Interestingly, this trial showed that sunitinib could be combined with
      somatostatin analogues without affecting the safety profile of either sunitinib
      or somatostatin analogues. Since the overall survival of patients with well
      differentiated neuroendocrine tumors remains sufficiently long, it is worth
      considering using alternate sequences of targeted therapy (such as everolimus)
      and chemotherapy to optimize the care of patients with advanced diseases. The
      optimal sequence for using chemotherapy, everolimus, and sunitinib will remain to
      be established in clinical trials.

PMID- 22661320
TI  - K27M mutation in histone H3.3 defines clinically and biologically distinct
      subgroups of pediatric diffuse intrinsic pontine gliomas.
AB  - Pediatric glioblastomas (GBM) including diffuse intrinsic pontine gliomas (DIPG)
      are devastating brain tumors with no effective therapy. Here, we investigated
      clinical and biological impacts of histone H3.3 mutations. Forty-two DIPGs were
      tested for H3.3 mutations. Wild-type versus mutated (K27M-H3.3) subgroups were
      compared for HIST1H3B, IDH, ATRX and TP53 mutations, copy number alterations and
      clinical outcome. K27M-H3.3 occurred in 71 %, TP53 mutations in 77 % and ATRX
      mutations in 9 % of DIPGs. ATRX mutations were more frequent in older children (p
      < 0.0001). No G34V/R-H3.3, IDH1/2 or H3.1 mutations were identified. K27M-H3.3
      DIPGs showed specific copy number changes, including all gains/amplifications of
      PDGFRA and MYC/PVT1 loci. Notably, all long-term survivors were H3.3 wild type
      and this group of patients had better overall survival. K27M-H3.3 mutation
      defines clinically and biologically distinct subgroups and is prevalent in DIPG,
      which will impact future therapeutic trial design. K27M- and G34V-H3.3 have
      location-based incidence (brainstem/cortex) and potentially play distinct roles
      in pediatric GBM pathogenesis. K27M-H3.3 is universally associated with short
      survival in DIPG, while patients wild-type for H3.3 show improved survival. Based
      on prognostic and therapeutic implications, our findings argue for H3.3-mutation
      testing at diagnosis, which should be rapidly integrated into the clinical
      decision-making algorithm, particularly in atypical DIPG.

PMID- 22661321
TI  - Ubiquilin immunoreactivity in cytoplasmic and nuclear inclusions in
      synucleinopathies, polyglutamine diseases and intranuclear inclusion body
      disease.

PMID- 22661322
TI  - Rewiring drug-activated p53-regulatory network from suppressing to promoting
      tumorigenesis.
AB  - Many of oncogenes and tumor suppressor genes have been found to exert variable
      and even opposing roles in different kinds of tumors or at different stages of
      cancer development. Here we showed that tumorigenic potential of mouse embryonic
      carcinoma P19 cells cultured in adherent plates (attached-P19-cells) was
      suppressed by a chemotherapeutic agent, 5-aza-2'-deoxycytidine (ZdCyd), whereas
      the higher pro-tumorigenicity of P19 cells growing in suspension (detached-P19
      cells) was generated by the ZdCyd treatment. Surprisingly, p53 activity was
      highly up-regulated by ZdCyd in both growing conditions. By our developed
      computational approaches, we revealed that there was a significant enrichment of
      apoptotic pathways in the ZdCyd-induced p53-dominant gene-regulatory network in
      attached P19 cells, whereas the pro-survival genes were significantly enriched in
      the ZdCyd-induced p53 network in detached P19 cells. The protein-protein
      interaction network of the ZdCyd-treated detached P19 cells was significantly
      different from that of ZdCyd-treated attached P19 cells. On the other hand,
      inhibition of p53 expression by siRNA suppressed the ZdCyd-induced tumorigenesis
      of detached P19 cells, suggesting that the ZdCyd-activated p53 plays oncogenic
      function in detached P19 cells. Taken together, these results indicate a context
      dependent role for the ZdCyd-activated p53-dominant network in tumorigenesis.

PMID- 22661323
TI  - Dynamics of neutral and selected alleles when the offspring distribution is
      skewed.
AB  - We analyze the dynamics of two alternative alleles in a simple model of a
      population that allows for large family sizes in the distribution of offspring
      number. This population model was first introduced by Eldon and Wakeley, who
      described the backward-time genealogical relationships among sampled individuals,
      assuming neutrality. We study the corresponding forward-time dynamics of allele
      frequencies, with or without selection. We derive a continuum approximation,
      analogous to Kimura's diffusion approximation, and we describe three distinct
      regimes of behavior that correspond to distinct regimes in the coalescent
      processes of Eldon and Wakeley. We demonstrate that the effect of selection is
      strongly amplified in the Eldon-Wakeley model, compared to the Wright-Fisher
      model with the same variance effective population size. Remarkably, an
      advantageous allele can even be guaranteed to fix in the Eldon-Wakeley model,
      despite the presence of genetic drift. We compute the selection coefficient
      required for such behavior in populations of Pacific oysters, based on estimates
      of their family sizes. Our analysis underscores that populations with the same
      effective population size may nevertheless experience radically different forms
      of genetic drift, depending on the reproductive mechanism, with significant
      consequences for the resulting allele dynamics.

PMID- 22661324
TI  - A resolution of the mutation load paradox in humans.
AB  - Current information on the rate of mutation and the fraction of sites in the
      genome that are subject to selection suggests that each human has received, on
      average, at least two new harmful mutations from its parents. These mutations
      were subsequently removed by natural selection through reduced survival or
      fertility. It has been argued that the mutation load, the proportional reduction
      in population mean fitness relative to the fitness of an idealized mutation-free
      individual, allows a theoretical prediction of the proportion of individuals in
      the population that fail to reproduce as a consequence of these harmful
      mutations. Application of this theory to humans implies that at least 88% of
      individuals should fail to reproduce and that each female would need to have more
      than 16 offspring to maintain population size. This prediction is clearly at odds
      with the low reproductive excess of human populations. Here, we derive
      expressions for the fraction of individuals that fail to reproduce as a
      consequence of recurrent deleterious mutation () for a model in which selection
      occurs via differences in relative fitness, such as would occur through
      competition between individuals. We show that  is much smaller than the value
      predicted by comparing fitness to that of a mutation-free genotype. Under the
      relative fitness model, we show that  depends jointly on U and the selective
      effects of new deleterious mutations and that a species could tolerate 10's or
      even 100's of new deleterious mutations per genome each generation.

PMID- 22661325
TI  - Quantile-based permutation thresholds for quantitative trait loci hotspots.
AB  - Quantitative trait loci (QTL) hotspots (genomic locations affecting many traits)
      are a common feature in genetical genomics studies and are biologically
      interesting since they may harbor critical regulators. Therefore, statistical
      procedures to assess the significance of hotspots are of key importance. One
      approach, randomly allocating observed QTL across the genomic locations
      separately by trait, implicitly assumes all traits are uncorrelated. Recently, an
      empirical test for QTL hotspots was proposed on the basis of the number of traits
      that exceed a predetermined LOD value, such as the standard permutation LOD
      threshold. The permutation null distribution of the maximum number of traits
      across all genomic locations preserves the correlation structure among the
      phenotypes, avoiding the detection of spurious hotspots due to nongenetic
      correlation induced by uncontrolled environmental factors and unmeasured
      variables. However, by considering only the number of traits above a threshold,
      without accounting for the magnitude of the LOD scores, relevant information is
      lost. In particular, biologically interesting hotspots composed of a moderate to
      small number of traits with strong LOD scores may be neglected as nonsignificant.
      In this article we propose a quantile-based permutation approach that
      simultaneously accounts for the number and the LOD scores of traits within the
      hotspots. By considering a sliding scale of mapping thresholds, our method can
      assess the statistical significance of both small and large hotspots. Although
      the proposed approach can be applied to any type of heritable high-volume "omic"
      data set, we restrict our attention to expression (e)QTL analysis. We assess and
      compare the performances of these three methods in simulations and we illustrate
      how our approach can effectively assess the significance of moderate and small
      hotspots with strong LOD scores in a yeast expression data set.

PMID- 22661328
TI  - Neutrality tests for sequences with missing data.
AB  - Missing data are common in DNA sequences obtained through high-throughput
      sequencing. Furthermore, samples of low quality or problems in the experimental
      protocol often cause a loss of data even with traditional sequencing
      technologies. Here we propose modified estimators of variability and neutrality
      tests that can be naturally applied to sequences with missing data, without the
      need to remove bases or individuals from the analysis. Modified statistics
      include the Watterson estimator thetaW, Tajima's D, Fay and Wu's H, and HKA. We
      develop a general framework to take missing data into account in frequency
      spectrum-based neutrality tests and we derive the exact expression for the
      variance of these statistics under the neutral model. The neutrality tests
      proposed here can also be used as summary statistics to describe the information
      contained in other classes of data like DNA microarrays.

PMID- 22661326
TI  - The importance of conserved features of yeast actin-binding protein 1 (Abp1p):
      the conditional nature of essentiality.
AB  - Saccharomyces cerevisiae Actin-Binding Protein 1 (Abp1p) is a member of the Abp1
      family of proteins, which are in diverse organisms including fungi, nematodes,
      flies, and mammals. All proteins in this family possess an N-terminal Actin
      Depolymerizing Factor Homology (ADF-H) domain, a central Proline-Rich Region
      (PRR), and a C-terminal SH3 domain. In this study, we employed sequence analysis
      to identify additional conserved features of the family, including sequences rich
      in proline, glutamic acid, serine, and threonine amino acids (PEST), which are
      found in all family members examined, and two motifs, Conserved Fungal Motifs 1
      and 2 (CFM1 and CFM2), that are conserved in fungi. We also discovered that,
      similar to its mammalian homologs, Abp1p is phosphorylated in its PRR. This
      phosphorylation is mediated by the Cdc28p and Pho85p kinases, and it protects
      Abp1p from proteolysis mediated by the conserved PEST sequences. We provide
      evidence for an intramolecular interaction between the PRR region and SH3 domain
      that may be affected by phosphorylation. Although deletion of CFM1 alone caused
      no detectable phenotype in any genetic backgrounds or conditions tested, deletion
      of this motif resulted in a significant reduction of growth when it was combined
      with a deletion of the ADF-H domain. Importantly, this result demonstrates that
      deletion of highly conserved domains on its own may produce no phenotype unless
      the domains are assayed in conjunction with deletions of other functionally
      important elements within the same protein. Detection of this type of intragenic
      synthetic lethality provides an important approach for understanding the function
      of individual protein domains or motifs.

PMID- 22661327
TI  - Dynamic mutation-selection balance as an evolutionary attractor.
AB  - The vast majority of mutations are deleterious and are eliminated by purifying
      selection. Yet in finite asexual populations, purifying selection cannot
      completely prevent the accumulation of deleterious mutations due to Muller's
      ratchet: once lost by stochastic drift, the most-fit class of genotypes is lost
      forever. If deleterious mutations are weakly selected, Muller's ratchet can lead
      to a rapid degradation of population fitness. Evidently, the long-term stability
      of an asexual population requires an influx of beneficial mutations that
      continuously compensate for the accumulation of the weakly deleterious ones.
      Hence any stable evolutionary state of a population in a static environment must
      involve a dynamic mutation-selection balance, where accumulation of deleterious
      mutations is on average offset by the influx of beneficial mutations. We argue
      that such a state can exist for any population size N and mutation rate U and
      calculate the fraction of beneficial mutations, epsilon, that maintains the
      balanced state. We find that a surprisingly low epsilon suffices to achieve
      stability, even in small populations in the face of high mutation rates and weak
      selection, maintaining a well-adapted population in spite of Muller's ratchet.
      This may explain the maintenance of mitochondria and other asexual genomes.

PMID- 22661329
TI  - Inhibition of c-Jun N-terminal kinase prevents blood-brain barrier disruption and
      normalizes the expression of tight junction proteins clautin-5 and ZO-1 in a rat
      model of subarachnoid hemorrhage.
AB  - BACKGROUND: The c-Jun N-terminal kinase (JNK) proteins are encoded by three genes
      (JNK1, JNK2, and JNK3), giving rise to multiple isoforms via alternative
      splicing. JNK inhibition using a chemical inhibitor SP600125 confers
      neuroprotection in an animal model of subarachnoid hemorrhage (SAH). The aim of
      this study is to investigate whether the protective effects of SP600125 were
      associated with modulation of tight junction proteins including claudin-5 and ZO
      1 and to define which JNK isoforms were involved in the early brain injury after
      SAH. METHODS: Seventy-five male Sprague Dawley rats (weighing 300-350 g) were
      randomly assigned to five groups (n = 15): (1) sham, (2) SAH, (3) SAH + DMSO
      (dimethyl sulfoxide), (4) SAH + 10 mg/kg SP600125, and (5) SAH + 30 mg/kg
      SP600125. SP600125 or DMSO was injected intraperitoneally 1 h before and 6 h
      after the induction of SAH. Animals from all the groups were killed 24 h after
      SAH, and brain tissues were dissected and subjected to electron microscopic
      examination, Western blot analysis, and histological evaluation. RESULTS:
      SP600125 pretreatment restored tight junctions and attenuated blood-brain barrier
      (BBB) disruption and cerebral edema after SAH, coupled with reduced apoptosis in
      the cerebral cortex. SP600125 exposure restored the reduced expression of both
      claudin-5 and ZO-1 following SAH and normalized the levels of JNK1 and JNK3.
      CONCLUSION: Our data demonstrate that the JNK signaling plays an important role
      in the regulation of tight junction proteins and BBB integrity, and thus
      represents a promising target against brain injuries after SAH.

PMID- 22661330
TI  - [Extensive interactions between eating and weight disorder,  major depression,
      pain, and sarcoidosis - case 5/2012].
AB  - HISTORY AND ADMISSION FINDINGS: We report on a 41-year-old female patient
      suffering from obesity, binge eating more than twice a week with loss of control,
      eating rapidly and feeling guilty after eating, dyspnoea and chronic pain in the
      whole body, especially in her arms, legs and in both ankles. Furthermore, subdued
      mood, loss of interest and pleasure, fatigue and impaired concentration could be
      recognized. In the past, weight increase had been observed when corticosteroids
      were given against exacerbations of sarcoidosis. INVESTIGATIONS: In the case of
      our patient, the beginning of sarcoidosis and increase of weight and pain
      correlated with augmentation of depression and psychosocial stress. Dysfunctional
      behavioral features and multiple interactions between diseases could be observed.
      DIAGNOSIS, TREATMENT AND COURSE: We diagnosed obesity, binge eating disorder,
      major depression, chronic pain disease with somatic and psychical components and
      sarcoidosis. The patient was treated in a multimodal therapy program including
      psychotherapy, pharmacotherapy and psychopharmacotherapy, nutritionist advice and
      therapeutic exercise. A weight loss of 7.9 kg (5.9 %), well-balanced diet,
      reduction of binge eating and of pain intensity, mood stabilization as well as
      perception and expression of emotions and coping strategies in chronic diseases
      were achieved. CONCLUSION: Interdisciplinary treatment of patients suffering from
      psychosomatic, somatic and mental diseases is crucial for a good outcome.

PMID- 22661331
TI  - Promoting the use of BaP as a marker for PAH exposure in UK soils.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants
      that frequently accumulate in soils. There is therefore a requirement to
      determine their levels in contaminated environments for the purposes of
      determining impacts on human health. PAHs are a suite of individual chemicals,
      and there is an ongoing debate as to the most appropriate method for assessing
      the risk to humans from them. Two methods predominate: the surrogate marker
      approach and the toxic equivalency factor. The former assumes that all chemicals
      in a mixture have an equivalent toxicity. The toxic equivalency approach
      estimates the potency of individual chemicals relative to the usually most toxic
      Benzo(a)pyrene. The surrogate marker approach is believed to overestimate risk
      and the toxic equivalency factor to underestimate risk. When analysing the risks
      from soils, the surrogate marker approach is preferred due to its simplicity, but
      there are concerns because of the potential diversity of the PAH profile across
      the range of impacted soils. Using two independent data sets containing soils
      from 274 sites across a diverse range of locations, statistical analysis was
      undertaken to determine the differences in the composition of carcinogenic PAH
      between site locations, for example, rural versus industrial. Following principal
      components analysis, distinct population differences were not seen between site
      locations in spite of large differences in the total PAH burden between
      individual sites. Using all data, highly significant correlations were seen
      between BaP and other carcinogenic PAH with the majority of r (2) values > 0.8.
      Correlations with the European Food Standards Agency (EFSA) summed groups, that
      is, EFSA2, EFSA4 and EFSA8 had even higher correlations (r (2) > 0.95). We
      therefore conclude that BaP is a suitable surrogate marker to represent mixtures
      of PAH in soil during risk assessments.

PMID- 22661334
TI  - Evaluation of a physical activity program for pathological gamblers in treatment.
AB  - It has been demonstrated that craving for gambling is associated with anxiety and
      depression in pathological gamblers. Exercise has been shown to reduce anxiety
      and depression, as well as positively influence abstinence rates in individuals
      with substance use disorders. In this study, we examined the impact of a physical
      activity program in 33 pathological gamblers. We also analyzed the association
      between craving and plasmatic levels of stress hormones (adrenocorticotropic
      hormone, cortisol, and prolactin). The program involved eight 50-min sessions.
      Craving was assessed 24 h before, immediately before, and immediately after each
      session, as well as on a weekly basis. Before and after the program, we evaluated
      gambling behavior, depressive symptoms, anxiety, and plasma levels of stress
      hormones. We identified a significant reduction in craving following each session
      and at the end of the program. There was improvement in anxiety, depressive
      symptoms, and gambling behavior. The post-session reduction in craving was
      accompanied by post-program reductions in craving and anxiety but not by a post
      program reduction in depressive symptoms. The craving reduction was associated
      with a variation in prolactin levels but not with variations in levels of
      cortisol or adrenocorticotropic hormone. 

PMID- 22661332
TI  - Should two-drug initial therapy for hypertension be recommended for all patients?
AB  - Hypertension is a common disorder linked to increases in cardiovascular mortality
      and morbidity. Effective treatment decreases this excess mortality. Therapy with
      a single antihypertensive agent fails to achieve blood pressure goals in up to 75
      % of patients. Compared to monotherapy, combination antihypertensive therapy,
      especially with fixed-dose (single pill) formulations, may more effectively
      control blood pressure and improve medication persistence while decreasing
      adverse effects, healthcare costs, and physician therapeutic inertia. Certain
      combinations, such as a calcium channel blocker and angiotensin converting enzyme
      inhibitor, have been associated with similar or fewer adverse effects and better
      outcomes than other combinations. In contrast, other combinations such as
      thiazide diuretics and beta-blockers may cause more adverse effects than
      monotherapy. When choosing a thiazide diuretic, chlorthalidone is preferable to
      hydrochlorothiazide, given better efficacy and cardiovascular outcomes. Initial
      combination antihypertensive therapy may benefit patients with stage I or II
      hypertension and more widespread use should be encouraged.

PMID- 22661335
TI  - Clinical pathways for pancreatic neuroendocrine tumors.
AB  - BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) represent a group of
      diseases that pose diagnostic and therapeutic challenges due to their clinical
      and pathological heterogeneity as well as the limited number of patients
      available for clinical trials. Over the last couple of decades, a major progress
      in understanding tumor biology led to the discovery of new potential targets for
      the medical treatment of these tumors. DISCUSSION: There are numerous novel
      targeted agents in various stages of preclinical and clinical development that
      offer considerable promise as monotherapy or combination therapy for PNETs. The
      question of whether traditional clinical research methods are appropriate for the
      development of novel, targeted anticancer agents has been the subject of many
      discussions. Major challenges include identifying a valid target, the most
      effective agent within a target class, the right subset of population to benefit
      from the drug, and the most appropriate setting to use the drug. As new agents
      emerge, oncologists are faced with making clinical decisions sometimes before
      having a high level of evidence. In this review, we attempt to address some of
      the management steps involved in treating patients with pancreatic neuroendocrine
      tumors, particularly well to moderately differentiated tumors. The purpose of
      this review is to offer a therapeutic sequence including surgery, liver-directed
      therapy, chemotherapy, and targeted therapy for this disease.

PMID- 22661336
TI  - A systematic review of randomized controlled clinical trials comparing hamstring
      autografts versus bone-patellar tendon-bone autografts for the reconstruction of
      the anterior cruciate ligament.
AB  - OBJECTIVES: Controversies exist over which type of graft is best for the
      reconstruction of the anterior cruciate ligament (ACL). The purpose of this
      systematic review was to evaluate the effectiveness of ACL reconstruction using
      either hamstring (HT) autografts or bone-patellar tendon-bone (BPTB) autografts.
      METHODS: We searched the Cochrane Library, MEDLINE and EMBASE for published
      randomized controlled trials (RCT) comparing HT autografts with BPTB autografts
      for ACL reconstruction. Data analyses were performed using Cochrane Collaboration
      RevMan 5.0. RESULTS: Nine RCTs (738 patients) met the inclusion criteria. The
      combined results of the meta-analysis indicated there was a significantly lower
      rate of negative Pivot test [relative risk (RR) 0.87, 95 % confidence intervals
      (CI) 0.79-0.96, P = 0.004], anterior knee pain (RR 0.66, 95 % CI 0.45-0.96, P =
      0.03) and of kneeling pain (RR 0.49, 95 % CI 0.27-0.91, P = 0.02) in the HT group
      than in the BPTB group. CONCLUSIONS: ACL reconstruction with HT autografts or
      BPTB autografts achieved similar postoperative effects in terms of restoring knee
      joint function. HT autografts were inferior to BPTB autografts for restoring knee
      joint stability, but were associated with fewer postoperative complications.

PMID- 22661338
TI  - Staged surgical palliation in identical twins with concordance for hypoplastic
      left heart syndrome (HLHS).

PMID- 22661337
TI  - Early pathogenic care and the development of ADHD-like symptoms.
AB  - Early pathogenic care that is characterised by disregard for the child's basic
      emotional needs can lead to severe global psychosocial and cognitive dysfunction
      and deviant developmental trajectories of brain maturation. Reactive attachment
      disorder (RAD) is a developmental disorder associated with early pathogenic care
      that is characterised by markedly disturbed ways of relating socially in most
      contexts. In addition to other severe emotional dysfunctions, children suffering
      from RAD often display a high number of comorbid attention deficit/hyperactivity
      disorder (ADHD) symptoms such as inattention, impulsivity and hyperactivity. It
      is not yet clear whether ADHD-like symptoms in children exposed to pathogenic
      care represent a true comorbidity of ADHD or similarities in behavioural
      dysfunction with a different neurodevelopmental pathway in terms of a phenocopy.
      In this review, we summarise the findings on the neurobiological consequences of
      early pathogenic care. Pathogenic care is considered a form of care by a primary
      caretaker involving a lack or a loss of expectable care, e.g., by early
      separation, frequent change in caregivers, institutionalisation or neglect. The
      reviewed studies suggest that a primary dysfunction of limbic brain circuits
      after early pathogenic care might lead to an interference by motivational or
      emotional cues impinging on prefrontal executive functions resulting in
      behavioural similarities with ADHD. Thus, the complex phenotype observed after
      early pathogenic care might be best described by a dimensional approach with
      behavioural and neurobiological similarities to ADHD coinciding to a certain
      degree as a function of early experience. Based on this evidence, suggestions for
      the treatment of ADHD-like symptoms in children after adverse early life
      experiences are provided.

PMID- 22661340
TI  - Management of proximal femoral focal deficiency with limited resources in Haiti.
AB  - BACKGROUND: Individuals with proximal femoral focal deficiency (PFFD) present
      with a shortened femur. This report highlights the process used to determine
      prosthetic candidacy, a novel use of the International Committee of the Red Cross
      (ICRC) prosthetic materials, and subsequent rehabilitation when treating in rural
      Haiti. CASE DESCRIPTION AND METHODS: An eight-year-old boy with PFFD whose goal
      was to walk 'normally' presented with a shortened right leg and typical
      foot/ankle. Concerns regarding ability to safely load the leg were mitigated
      after finding he could fully load his right limb, control motion, and had no
      fractures. FINDINGS AND OUTCOMES: A unique prosthosis incorporating a donated
      hinged ankle-foot orthosis, ICRC materials and a SACH foot was fabricated.
      Physical therapy followed for two weeks, progressing from static weight-bearing
      and gait training to dynamic balance activities. At discharge, the patient walked
      independently using the prosthosis and one forearm crutch. CONCLUSION: Through
      collaboration and innovation rehabilitation goals can be realized even when
      presented with limited resources. Clinical relevance Through collaboration and
      innovation novel prosthetic designs incorporating materials from the
      International Committee of the Red Cross can be created and rehabilitation goals
      can be realized even when presented with limited resources.

PMID- 22661339
TI  - Enterococcal endocarditis: can we win the war?
AB  - Treatment of enterococcal infections has long been recognized as an important
      clinical challenge, particularly in the setting of infective endocarditis (IE).
      Furthermore, the increase prevalence of isolates exhibiting multidrug resistance
      (MDR) to traditional anti-enterococcal antibiotics such as ampicillin, vancomycin
      and aminoglycosides (high-level resistance) poses immense therapeutic dilemmas in
      hospitals around the world. Unlike IE caused by most isolates of Enterococcus
      faecalis, which still retain susceptibility to ampicillin and vancomycin, the
      emergence and dissemination of a hospital-associated genetic clade of multidrug
      resistant Enterococcus faecium, markedly limits the therapeutic options. The best
      treatment of IE MDR enterococcal endocarditis is unknown and the paucity of
      antibiotics with bactericidal activity against these organisms is a cause of
      serious concern. Although it appears that we are winning the war against E.
      faecalis, the battle rages on against isolates of multidrug-resistant E. faecium.

PMID- 22661341
TI  - Self-reported work ability and work performance in workers with chronic
      nonspecific musculoskeletal pain.
AB  - PURPOSE: To assess self-reported work ability and work performance of workers who
      stay at work despite chronic nonspecific musculoskeletal pain (CMP), and to
      explore which variables were associated with these outcomes. METHODS: In a cross
      sectional study we assessed work ability (Work Ability Index, single item scale 0
      10) and work performance (Health and Work Performance Questionnaire, scale 0-10)
      among 119 workers who continued work while having CMP. Scores of work ability and
      work performance were categorized into excellent (10), good (9), moderate (8) and
      poor (0-7). Hierarchical multiple regression and logistic regression analysis was
      used to analyze the relation of socio-demographic, pain-related, personal- and
      work-related variables with work ability and work performance. RESULTS: Mean work
      ability and work performance were 7.1 and 7.7 (poor to moderate). Hierarchical
      multiple regression analysis revealed that higher work ability scores were
      associated with lower age, better general health perception, and higher pain self
      efficacy beliefs (R(2) = 42 %). Higher work performance was associated with lower
      age, higher pain self-efficacy beliefs, lower physical work demand category and
      part-time work (R(2) = 37 %). Logistic regression analysis revealed that work
      ability >=8 was significantly explained by age (OR = 0.90), general health
      perception (OR = 1.04) and pain self-efficacy (OR = 1.15). Work performance >=8
      was explained by pain self-efficacy (OR = 1.11). CONCLUSIONS: Many workers with
      CMP who stay at work report poor to moderate work ability and work performance.
      Our findings suggest that a subgroup of workers with CMP can stay at work with
      high work ability and performance, especially when they have high beliefs of pain
      self-efficacy. Our results further show that not the pain itself, but personal
      and work-related factors relate to work ability and work performance.

PMID- 22661343
TI  - Training under the wing of many masters.

PMID- 22661344
TI  - The pharmacological treatment of acquired nystagmus.
AB  - We review the latest literature on the neuropharmacological treatments for
      acquired nystagmus.Nystagmus may have a significant [corrected] impact on health,
      yet there is little scientific evidence on which to make firm recommendations for
      treatment. Acquired pendular nystagmus may respond to gabapentin or memantine;
      downbeat and upbeat nystagmus to aminopyridines; and periodic alternating
      nystagmus to baclofen. To improve treatment we need multi-centre, randomised
      controlled trials using standardised techniques in reporting objective outcomes,
      with good follow-up duration and careful reporting of side effects.

PMID- 22661345
TI  - Practical neurology.

PMID- 22661346
TI  - Acute symptomatic seizures.
AB  - Acute symptomatic seizures occur in close temporal proximity to a documented
      neurological or systemic insult. They are a common reason for seeking an
      emergency neurological opinion. We discuss their important causes, treatment and
      prognosis, discuss a practical approach to their clinical assessment and
      investigation, and offer thoughts on treatment.

PMID- 22661347
TI  - Reflections: the strategy of preventive medicine.

PMID- 22661349
TI  - Four eponyms in coma.

PMID- 22661348
TI  - Respiratory management of motor neurone disease: a review of current practice and
      new developments.
AB  - Motor neurone disease is a neurodegenerative condition with a significant
      morbidity and shortened life expectancy. Hypoventilatory respiratory failure is
      the most common cause of death and respiratory function significantly predicts
      both survival and quality of life in patients with motor neurone disease.
      Accordingly, supporting and maintaining respiratory function is important in
      caring for these patients. The most significant advance in motor neurone disease
      care of recent years has been the domiciliary provision of non-invasive
      ventilation for treating respiratory failure. Neuromuscular respiratory weakness
      also leads to ineffective cough and retained airways secretions, predisposing to
      recurrent chest infections. In this review, we discuss current practice and
      recent developments in the respiratory management of motor neurone disease, in
      terms of ventilatory support and cough augmentation.

PMID- 22661350
TI  - Stroke mimicking conversion disorder: two young women who put our feet back on
      the ground.
AB  - We describe two young female patients with symptoms and signs initially of
      conversion disorder. It became apparent, however, that both patients had a
      posterior circulation stroke. These cases remind us of just how broad the
      clinical presentation of neurological diseases is and illustrate how careful we
      must be in our own attributions, actions and diagnoses particularly when
      assessing patients with bizarre behaviour and with apparent inconsistencies on
      neurological examination.

PMID- 22661351
TI  - Knee bobbing in Charcot-Marie-Tooth disease.
AB  - Patients with Charcot-Marie-Tooth (CMT) disease most commonly have a slowly
      progressive neuropathy where ankle dorsiflexion weakness is much more prominent
      than ankle plantar flexion weakness. The eventual involvement of the ankle
      plantar flexors has major functional consequences for patients as they lose the
      ability to stand still. We have found the knee bob sign whereby both knees bob up
      and down when standing still to be a reliable marker of ankle plantar flexion
      weakness in CMT.

PMID- 22661352
TI  - Paradoxical abdominal wall movement in bilateral diaphragmatic paralysis.
AB  - A 56-year-old man gave a 6-month history of progressive dyspnoea and orthopnoea.
      During breathing, his abdominal muscles showed paradoxical movement and he
      rapidly and reproducibly developed difficulty breathing when lying supine. The
      most likely explanation was severe weakness or paralysis of both hemidiaphragms.
      This was confirmed with electrophysiology and ultrasonography. Extensive
      investigation identified no underlying cause, suggesting this is a case of
      bilateral isolated phrenic neuropathy. We present a video showing how easily
      bilateral diaphragmatic palsy can be detected clinically through identifying
      paradoxical abdominal wall movement.

PMID- 22661353
TI  - The fundamentals of electromyography.

PMID- 22661354
TI  - Multiple cranial neuropathies: one diagnostic difficulty.

PMID- 22661355
TI  - Torsade de pointes in Kearns-Sayre syndrome.
AB  - A 47-year-old woman with Kearns-Sayre syndrome (KSS) and an implanted pacemaker
      for complete heart block was admitted to the intensive care unit following a
      cardiac arrest due to ventricular tachycardia (torsade de pointes) in the setting
      of QT prolongation. Complete heart blocks and ventricular tachycardia are
      implicated as mechanisms of sudden deaths in KSS; such patients may require
      pacemaker implantation and implantation of an automatic implantable cardioverter
      defibrillator.

PMID- 22661356
TI  - Prosoflagnosia?

PMID- 22661357
TI  - Pathogenesis of secondary hyperparathyroidism and fibroblast growth factor 23: a
      pharmacological validation of the "trade-off hypothesis".

PMID- 22661358
TI  - Water quality characterization in the Northern Florida everglades based on three
      different monitoring networks.
AB  - The Loxahatchee National Wildlife Refuge (Refuge) is affected by inflows
      containing elevated contaminant concentrations originating from agricultural and
      urban areas. Water quality was determined using three networks: the Northern
      Refuge (NRN), the Southern Refuge (SRN), and the Consent Decree (CDN) monitoring
      networks. Within these networks, the Refuge was divided into four zones: (1) the
      canal zone surrounding the marsh, (2) the perimeter zone (0 to 2.5 km into the
      marsh), (3) the transition zone (2.5 to 4.5 km into the marsh), and (4) the
      interior zone (>4.5 km into the marsh). In the NRN, alkalinity (ALK) and
      conductivity (SpC) and dissolved organic carbon, total organic carbon, total
      dissolved solids (TDS), Ca, Cl, Si, and SO(4) concentrations were greater in the
      perimeter zone than in the transition or interior zone. ALK, SpC, and SO(4)
      concentrations were greater in the transition than in the interior zone. ALK,
      SpC, and TDS values, Ca, SO(4), and Cl had negative curvilinear relationships
      with distance from the canal toward the Refuge interior (r(2) = 0.78, 0.67, 0.61,
      0.77, 0.62, and 0.57, respectively). ALK, TB and SpC, and Ca and SO(4)
      concentrations decreased in the canal and perimeter zones from 2005 to 2009.
      Important water quality assessments using the SRN and CDN cannot be made due to
      the sparseness and location of sampling sites in these networks. The number and
      placement monitoring sites in the Refuge requires optimization based on flow
      pattern, distance from contaminant source, and water volume to determine the
      effect of canal water intrusion on water quality.

PMID- 22661359
TI  - Distribution and potential sources of polycyclic aromatic hydrocarbons in soils
      around coal-fired power plants in South Africa.
AB  - The distribution and potential sources of 15 polycyclic aromatic hydrocarbons
      (PAHs) in soils in the vicinity of three South African coal-fired power plants
      were determined by gas chromatography-mass spectrometry. PAH compound ratios such
      as phenanthrene/phenanthrene + anthracene (Phen/Phen + Anth) were used to provide
      reliable estimation of emission sources. The total PAH concentration in the soils
      around three power plants ranged from 9.73 to 61.24 MUg g(-1), a range above the
      Agency for Toxic Substances and Disease Registry levels of 1.0 MUg g(-1) for
      significantly contaminated site. Calculated values of Phen/Phen + Anth ratio were
      0.48 +/- 0.08, 0.44 +/- 0.05, and 0.38 + 0.04 for Matla, Lethabo, and Rooiwal,
      respectively. Flouranthene/fluoranthene + pyrene (Flan/Flan + Pyr) were found to
      be 0.49 +/- 0.03 for Matla, 0.44 +/- 0.05 for Lethabo, and 0.53 +/- 0.08 for
      Rooiwal. Such values indicate a pyrolytic source of PAHs. Higher molecular weight
      PAHs (five to six rings) were predominant, suggesting coal combustion sources. A
      good correlation existed between most of the PAHs implying that these compounds
      were emitted from similar sources. The carcinogenic potency B[a]P equivalent
      concentration (B[a] Peq) at the three power plants ranged from 3.61 to 25.25
      indicating a high carcinogenic burden. The highest (B[a] Peq) was found in
      samples collected around Matla power station. It can therefore be concluded that
      the soils were contaminated with PAHs originating from coal-fired power stations.

PMID- 22661360
TI  - Combined paraesophageal hernia repair and partial longitudinal gastrectomy in
      obese patients with symptomatic paraesophageal hernias.
AB  - BACKGROUND: Obesity is a risk factor for gastroesophageal reflux disease and
      hiatal hernia. Studies have demonstrated poor symptom control in obese patients
      undergoing fundoplication. The ideal operation remains elusive. However,
      addressing both obesity and the anatomic abnormality should be the goal. METHODS:
      This study retrospectively identified 19 obese (body mass index [BMI], >30
      kg/m(2)) and morbidly obese (BMI, >40 kg/m(2)) patients who presented between
      December 2007 and November 2011 for management of large or recurrent
      paraesophageal hernia. All the patients underwent a combined primary
      paraesophageal hernia repair and longitudinal gastrectomy. Charts were
      retrospectively reviewed to collect preoperative, operative, and short-term
      postoperative results. Quantitative data were analyzed using Student's t test and
      qualitative data with chi(2) testing. RESULTS: Laparoscopy was successful for all
      19 patients. The mean preoperative BMI was 37.8 +/- 4.1 kg/m(2), and the mean
      operative time was 236 +/- 80 min. Preoperative endoscopy showed that 5 patients
      who had undergone prior fundoplication experienced anatomic failures, whereas the
      remaining 14 patients had type 3 and one type 4 paraesophageal Hernia. Mesh was
      used to reinforce the hiatus in 15 of the 19 cases. The postoperative
      complications included pulmonary embolism (n = 1) and pulmonary decompensation (n
      = 2) due to underlying chronic obstructive pulmonary disease. The mean hospital
      stay was 5.3 +/- 3 days. Upper gastrointestinal esophagography was performed for
      all the patients, with no short-term recurrence of paraesophageal hernia. Weight
      loss was seen for all the patients during the first month, with a mean BMI drop
      of 2.7 +/- 1 kg/m(2). All the patients experienced near to total resolution of
      their preoperative symptoms within the first month. CONCLUSION: Combined
      laparoscopic paraesophageal hernia repair and longitudinal gastrectomy offer a
      safe and feasible approach for the management of large or recurrent
      paraesophageal hernias in well-selected obese and morbidly obese patients. In a
      short-term follow-up period, this approach demonstrated effective symptom control
      and weight loss.

PMID- 22661372
TI  - [New leadership of the German Roentgen Society (interview by Dr. Claudia Gampe
      Braig)].

PMID- 22661362
TI  - [Epiploic appendagitis - appendicitis epiploica: benign differential diagnosis of
      acute abdomen].

PMID- 22661373
TI  - [Reassessment after change in continuing education regulation? Execution and
      billing of interventional radiologic procedures by angiologists].

PMID- 22661361
TI  - Lipoxin A4 inhibits 5-lipoxygenase translocation and leukotrienes biosynthesis to
      exert a neuroprotective effect in cerebral ischemia/reperfusion injury.
AB  - Lipoxin A(4) (LXA(4)), a biologically active eicosanoid with anti-inflammatory
      and pro-resolution properties, was recently found to have neuroprotective effects
      in brain ischemia. As 5-lipoxygenase (5-LOX) and leukotrienes are generally
      considered to aggravate cerebral ischemia/reperfusion (I/R) injury, we
      investigated their effects on LXA(4)-mediated neuroprotection by studying middle
      cerebral artery occlusion (MCAO)/reperfusion in rats and oxygen-glucose
      deprivation (OGD)/recovery in neonatal rat astrocyte primary cultures. LXA(4)
      effectively reduced infarct volumes and brain edema, and improved neurological
      scores in the MCAO/reperfusion experiments; this effect was partially blocked by
      butoxycarbonyl-Phe-Leu-Phe-Leu-Phe (Boc2), a specific antagonist of the LXA(4)
      receptor (ALXR). Total 5-LOX expression did not change, regardless of treatment,
      but LXA(4) could inhibit nuclear translocation induced by MCAO or OGD. We also
      found that LXA(4) inhibits the upregulation of both leukotriene B(4) (LTB(4)) and
      leukotriene C(4) (LTC(4)) and the phosphorylation of extracellular signal
      regulated kinase (ERK) induced by MCAO or OGD. The phosphorylation of the 38-kDa
      protein kinase (p38) and c-Jun N-terminal kinase (JNK) was not altered throughout
      the experiment. These results suggest that the neuroprotective effects of LXA(4)
      are probably achieved by anti-inflammatory mechanisms that are partly mediated by
      ALXR and through an ERK signal transduction pathway.

PMID- 22661375
TI  - A novel miRNA produced during lytic HSV-1 infection is important for efficient
      replication in tissue culture.
AB  - The influence of miRNAs on the host-pathogen environment is largely unknown and
      under intensive investigation. Whether produced by the pathogen or by the host
      cell, these miRNAs will sculpt the intracellular landscape, as their activity
      will ultimately affect levels of target proteins. Using a high-throughput
      sequencing approach, we identified 19 novel small RNAs produced during the early
      hours of herpes simplex virus type 1 (HSV-1) infection in epithelial cells. Six
      of the novel RNAs had predicted folds characteristic of miRNAs. One of the six,
      miR-92944, which resides in the 5' UTR of the ul42 gene in the sense orientation,
      was confirmed as a bona fide miRNA by RT-PCR and stem-loop PCR analysis. Northern
      blot analysis was used to observe the precursor forms of miR-92944. Viral mutants
      that do not produce miR-92944 exhibited significant reductions in viral titers in
      both single and multi-step growth analysis and a fourfold reduction in plaque
      size. The miR-92944 mutants produce wild-type levels of ICP4, UL42, VP5, and gC
      proteins contain no additional changes in the DNA sequence surrounding the site
      of mutagenesis. The defective phenotype of miR-92944 mutants was complemented in
      V42.3 cells, which contain the 5'UTR of ul42. We also found that miR-H1
      expression was diminished in cells infected with the miR-92944 mutant virus. This
      study provides new information on the miRNA landscape during the early stages of
      HSV-1 infection and reveals novel targets for antagonistic molecules that may
      curtail the establishment of lytic or latent virus infection.

PMID- 22661376
TI  - Molecular epidemiology of rabies in Ukraine.
AB  - To investigate the circulation of rabies virus in Ukraine, 78 rabies virus
      isolates were acquired from 14 states in 2002 and 2008-2010 for characterization.
      Partial sequences of nucleoprotein (359 nt) and glycoprotein (344 nt) genes were
      compared with those from neighbouring countries. The analysis identified 39
      unique nucleoprotein genes and two geographically distinct RV variants belonging
      to the cosmopolitan lineage. The Ukrainian samples were similar to the North-East
      European lineage (NEE) (n = 19) and Russian group C (n = 20). The group C viruses
      were mainly isolated in Eastern Ukraine, from 9 regions, and from two other
      regions in Western Ukraine, suggesting the presence of group C throughout the
      country. These group C viruses are intermixed in bordering regions along the
      Dnieper River with viruses of group NEE, which were mainly isolated in six
      regions in Western Ukraine. Both nucleoprotein and glycoprotein gene analyses
      suggested evidence for cross-border movements of rabies virus.

PMID- 22661377
TI  - Complete genome sequence of switchgrass mosaic virus, a member of a proposed new
      species in the genus Marafivirus.
AB  - The complete genome sequence of a virus recently detected in switchgrass (Panicum
      virgatum) was determined and found to be closely related to that of maize rayado
      fino virus (MRFV), genus Marafivirus, family Tymoviridae. The genomic RNA is 6408
      nucleotides long. It contains three predicted open reading frames (ORFs 1-3),
      encoding proteins of 227 kDa, 43.9 kDa, and 31.5 kDa, compared to two ORFs (1 and
      2) for MRFV. The complete genome shares 76 % sequence identity with MRFV. The
      nucleotide sequence of ORF2 of this virus and the amino acid sequence of its
      encoded protein are 49 % and 77 % identical, respectively, to those of MRFV. The
      virus-encoded polyprotein and capsid protein aa sequences are 83 % and 74-80 %
      identical, respectively, to those of MRFV. Although closely related to MRFV, the
      amino acid sequence of its capsid protein (CP) forms a clade that is separate
      from that of MRFV. Based on the International Committee on Taxonomy of Viruses
      (ICTV) sequence-related criteria for delineation of species within the genus
      Marafivirus, the virus qualifies as a member of a new species, and the name
      Switchgrass mosaic virus (SwMV) is proposed.

PMID- 22661378
TI  - Botulinum toxin for the treatment of movement disorders.
AB  - After botulinum toxin was initially used to treat strabismus in the 1970s, others
      started using it to treat movement disorders including blepharospasm, hemifacial
      spasm, cervical dystonia, spasmodic dysphonia, and oromandibular dystonia. It was
      discovered that botulinum toxin can be an effective treatment for focal movement
      disorders with limited side effects. Over the past three decades, various
      formulations of botulinum toxin have been developed and the therapeutic use of
      these toxins has expanded in movement disorders and beyond. We review the history
      and mechanism of action of botulinum toxin, as well as describe different
      formulations available and their potential therapeutic uses in movement
      disorders.

PMID- 22661379
TI  - Catalase and estradiol inhibit mitochondrial protein S-glutathionylation.
AB  - Regulation and downstream effects of mitochondrial protein S-glutathionylation in
      response to oxidative stress are poorly understood. The study aim was to
      determine whether anti-oxidants such as catalase and estradiol alter
      mitochondrial protein S-glutathionylation and in turn affect apoptosis following
      ultraviolet B (UV-B) light irradiation. HeLa cells were transduced with
      increasing amounts of adenovirus encoding catalase (Ad-Cat) and beta
      galactosidase (Ad-Lac Z) or pre-incubated with estradiol before induction of
      apoptosis by UV-B light exposure. Inhibition of mitochondrial protein S
      glutathionylation was assessed using autoantibodies specific for the non-S
      glutathionylated form of PDC-E2. The percentage of apoptotic cells following UV-B
      irradiation were not significantly different between mock cells (cells with no
      virus infection) and Ad-Cat and Ad-Lac Z infected cells at all viral doses (all p
      > 0.050). Autoantibody staining of non-S-glutathionylated PDC-E2 in apoptotic
      cells was three times greater in only Ad-Cat infected cells compared to only Ad
      Lac Z infected cells (81.3 +/- 16.7 vs 26 +/- 7.2 %, respectively, p = 0.030).
      Similarly estradiol treatment (33 and 100 nM) also significantly increased PDC-E2
      staining in apoptotic cells compared to non-treated cells (both p < 0.010). The
      percentage of apoptotic cells was not significantly different with any of the
      estradiol concentrations (all p > 0.100). The observed procaspase 12 cleavage
      following UV-B irradiation suggests that a mitochondrial-independent apoptotic
      pathway was activated. In conclusion, following an apoptotic stimulus, estradiol
      may inhibit mitochondrial protein S-glutathionylation without inhibiting
      apoptosis. This effect may play a role in ninefold greater prevalence of
      autoantibodies against PDC-E2 in women with primary biliary cirrhosis.

PMID- 22661380
TI  - Isogenic mesenchymal stem cells transplantation improves a rat model of chronic
      aristolochic acid nephropathy via upregulation of hepatic growth factor and
      downregulation of transforming growth factor beta1.
AB  - Chronic aristolochic acid (AA) nephropathy (CAAN) caused by intake of AA
      containing herbs is difficult to treat. We evaluated the therapeutic effect of
      bone marrow (BM) mesenchymal stem cells (MSCs) on a rat model of CAAN. Female
      Wistar rats were fed with decoction of Caulis Aristolochia manshuriensis by
      intragastric administration. MSCs were prepared from BM of male Wistar rats and
      injected into female CAAN rats through tail vein. Body weight, renal function,
      and urinary excretion of these CAAN rats were monitored before killing at the end
      of the 20th week. Blood, urine, and tissue samples were collected from
      experimental (MSC and non-MSC) and normal control groups. All animals developed
      renal fibrosis after 12 weeks of intake of AA-containing decoction. Fibrosis in
      the MSC groups was significantly reduced as examined with light and electron
      microscopy. Blood urea nitrogen, serum creatinine, and urine protein levels were
      significantly reduced and hemoglobin levels were improved in the MSC group as
      compared with the non-MSC group (p < 0.01). The expression of TGF-beta1 mRNA and
      protein was reduced but hepatic growth factor (HGF) was increased in the MSC
      group compared with the non-MSC group, but still higher than the normal control
      level as measured by immunochemical, RT-PCR, and western blotting assays (p <
      0.01). The renal fibrosis of CAAN could be protected by isogenic MSC
      transplantation, probably via upregulation of HGF and downregulation of TGF
      beta1.

PMID- 22661382
TI  - Current ultrafiltration techniques before, during and after pediatric
      cardiopulmonary bypass procedures.
AB  - Ultrafiltration, which is currently considered as a standard method to remove
      excess water administered during pediatric cardiopulmonary bypass (CPB), aims to
      minimize the adverse effects of hemodilution, such as tissue edema and blood
      transfusion. Three ultrafiltration techniques can be used before, during and
      after CPB procedures, including conventional ultrafiltration (CUF), modified
      ultrafiltration (MUF) and zero-balance ultrafiltration (Z-BUF). These methods are
      widely different, but they have common benefits on hemoconcentration, less
      requirement for blood products, and reduction of the systemic inflammatory
      responses (SIRS). The present review attempts to restate these ultrafiltration
      circuitries, application methods, end-points, and clinical impacts.

PMID- 22661381
TI  - Lactobacillus protected bone damage and maintained the antioxidant status of
      liver and kidney homogenates in female wistar rats.
AB  - The aim of the study was to evaluate protective property of Lactobacillus casei
      and Lactobacillus acidophilus in minimizing oxidative stress associated with
      arthritis from liver and kidney. Subsequently, protective property of
      Lactobacillus against the bone damage was also taken into consideration.
      Arthritis was induced by injecting freund's complete adjuvant (100 MUl) into sub
      plantar surface of hind paw. Oral administration of culture, vehicle, and drug
      started after induction of arthritis (i.e. on day 9th). Indomethacin was used as
      a standard drug. Radiographic analysis of the hind paw knee joint was also done
      at the end of the 21st day. Oxidative stress parameters were studied from liver
      and kidney homogenate. Histopathology of liver and kidney was also performed.
      Lactobacillus treatment significantly rescued the enzymatic level of catalase,
      superoxide dismutase, reduced glutathione, and glutathione peroxidase in both
      liver and kidney homogenates, whereas it has decreased the malonaldehyde
      accumulation. Oral administration of Lactobacillus also significantly decreased
      the serum ceruloplasmin level. Radiographic analysis also corroborated these
      findings. Lactobacillus treatment maintained the normal histopathology of liver
      and kidney. Results of this study clearly suggest that L. casei and L.
      acidophilus, alone or in combination, decreased the bone damaged and effectively
      restored antioxidant status of liver and kidney. Lactobacillus has a significant
      antiarthritic and antioxidant activity against freund's complete adjuvant induced
      arthritis in rats.

PMID- 22661383
TI  - Expression of SIRT1 is associated with lymph node metastasis and poor prognosis
      in both operable triple-negative and non-triple-negative breast cancer.
AB  - Several researches reported that overexpression of SIRT1 was associated with poor
      survival in several human cancers. However, some researches reported that SIRT1
      had an antitumor potential. The definite role of SIRT1 is not clear now, and few
      studies have documented the value of SIRT1 in triple-negative breast cancer
      (TNBC). Therefore, the aim of this study is to evaluate the role of SIRT1 in TNBC
      and non-TNBC for prognosis. A total of 51 TNBC patients and 83 non-TNBC patients
      who were diagnosed from October 2001 to September 2006 were involved in this
      study. Immunohistochemical staining for SIRT1 and p53 on tissue microarrays were
      used. Expression of SIRT1 was seen in 55 % of TNBC patients and 53 % of non-TNBC
      patients. Expression of SIRT1 was associated with lymph nodes status, stage,
      distant metastatic relapse, and p53 status in TNBC patients. Expression of SIRT1
      in non-TNBC patients was significantly correlated with lymph nodes status, age,
      stage, distant metastatic relapse, PR status, and p53 status. SIRT1+ group was
      associated with shorter DFS and OS compared with SIRT1- group in TNBC, non-TNBC,
      and overall breast cancer patients, according to univariate Cox regression
      analysis. Our study provides evidence that expression of SIRT is associated with
      worse prognosis in TNBC and non-TNBC and SIRT1 could be a potential therapeutic
      target in breast cancer.

PMID- 22661384
TI  - Systemic mastocytosis: progressive evolution of an occult disease into fatal mast
      cell leukemia: unique findings on an unusual hematological neoplasm.
AB  - Systemic mastocytosis (SM) may be associated with a clonal hematopoietic non-mast
      cell-lineage disease (AHNMD). SM and AHNMD even may be clonally related. This
      report contributes to a better understanding of the different morphological
      aspects of SM by demonstrating that various AHNMDs can be detected in one patient
      during the course of disease. Routinely processed biopsy specimens of bone marrow
      and spleen removed from a 63-year-old man were investigated including a broad
      panel of immunohistochemical stainings. KIT codon 816 mutation analysis was
      carried out by melting point analysis of nested PCR products amplified from DNA
      of pooled microdissected mast cells. The histomorphological features of the
      initial bone marrow showed diffuse infiltration by hairy cell leukemia (HCL).
      Occult SM was only detected retrospectively by demonstration of a slight diffuse
      increase in loosely scattered, spindle-shaped mast cells carrying the activating
      point mutation KIT ( D816V ). In the second bone marrow, core biopsy removed
      about two years later HCL had been completely eradicated, while a diagnosis of SM
      AHNMD with multifocal compact mast cell infiltrates associated with a
      myeloproliferative neoplasm (MPN) and significant increase in eosinophilic
      granulocytes was established. The third and last bone marrow biopsy specimen
      lacked the features of both MPN and HCL but showed progression into a secondary
      mast cell leukemia (MCL) with a focal sarcomatous component. To the best of the
      authors' knowledge, this is the first description of a case of SM-AHNMD with
      coexisting hematological neoplasms of lymphatic and myeloid origin initially
      presenting as occult disease and terminating as secondary MCL.

PMID- 22661386
TI  - [Tracking juvenile colonic polyps with hydro-sonograph and hydro-MRI].

PMID- 22661387
TI  - Acute carpal tunnel syndrome from dissected and thrombosed persistent median
      artery diagnosed at magnetic resonance imaging.

PMID- 22661388
TI  - [A combination of intratracheal and lateral cervical goiter as a special form of
      goiter recurrence in a 71-year-old patient].

PMID- 22661389
TI  - [Pulmonary edema in pulmonary leukostasis in acute myeloid leukemia].

PMID- 22661385
TI  - Computer-aided antibody design.
AB  - Recent clinical trials using antibodies with low toxicity and high efficiency
      have raised expectations for the development of next-generation protein
      therapeutics. However, the process of obtaining therapeutic antibodies remains
      time consuming and empirical. This review summarizes recent progresses in the
      field of computer-aided antibody development mainly focusing on antibody
      modeling, which is divided essentially into two parts: (i) modeling the antigen
      binding site, also called the complementarity determining regions (CDRs), and
      (ii) predicting the relative orientations of the variable heavy (V(H)) and light
      (V(L)) chains. Among the six CDR loops, the greatest challenge is predicting the
      conformation of CDR-H3, which is the most important in antigen recognition.
      Further computational methods could be used in drug development based on crystal
      structures or homology models, including antibody-antigen dockings and energy
      calculations with approximate potential functions. These methods should guide
      experimental studies to improve the affinities and physicochemical properties of
      antibodies. Finally, several successful examples of in silico structure-based
      antibody designs are reviewed. We also briefly review structure-based antigen or
      immunogen design, with application to rational vaccine development.

PMID- 22661390
TI  - [Clinical importance of CT-assisted sympathicolysis in primary, focal plantar and
      palmar hyperhidrosis].
AB  - PURPOSE: The objective of this study was to evaluate the benefit of thoracic and
      lumbar computed tomographic-assisted sympathicolysis (CTSy) in patients with
      primary, focal hyperhidrosis. MATERIALS AND METHODS: Thoracic and/or lumbar CTSy
      was conducted on 101 patients (average age 37.5 +/- 15.5 years) with primary,
      focal hyperhidrosis of the hands and/or feet, who experienced persistent symptoms
      after all conservative treatment options had been exhausted. The patients were
      divided into groups with palmar, palmoplantar and plantar hyperhidrosis. The
      patients evaluated the severity of their symptoms prior to the intervention and 2
      days, 6 months and 12 months after the intervention using a Dermatology Quality
      of Life Index (DLQI) and side effects. RESULTS: The performed interventions led
      to a statistically significant decrease in the preinterventional severity of
      symptoms after the intervention (2 days), and 6 and 12 months after CTSy in the
      palmar, palmoplantar and plantar (p < 0.01) group. The technical success rate of
      CTSy was 100 %. No major complications occurred. Patients reported compensatory
      perspiration over the course of treatment, neuralgia and paraesthesia as side
      effects. The differentiated assessment of the strength of perspiration of the
      hands and feet showed statistically significant differences between the foot and
      hand region, whereby the decrease in sweat secretion of the feet was more
      significant and more lasting (p < 0.02). CONCLUSION: After conservative measures
      have been exhausted, CT-assisted sympathicolysis represents a therapeutic option
      with minimal side effects for patients with primary, focal hyperhidrosis.

PMID- 22661391
TI  - Mucosal melanoma: pathogenesis, clinical behavior, and management.
AB  - Mucosal melanoma represents a rare subtype of melanoma with distinct biological,
      clinical, and management considerations. Knowledge regarding optimal treatment
      strategies for mucosal melanoma is limited and based primarily upon small case
      series and single-institution, retrospective analyses. Surgery remains the
      standard of care for loco-regional management, but the common presence of
      multifocal disease and the high rate of distant recurrence should be considered
      before pursuing aggressive surgical interventions associated with inherent
      significant morbidity. The role of sentinel lymph node biopsy and lymph node
      dissection remains unclear. Radiotherapy has not been shown to improve overall
      survival but may reduce the rate of local recurrence. Significant advances in the
      treatment of metastatic disease have been made with novel immunotherapeutic
      agents, the discovery of KIT and BRAF mutations and the development of targeted
      agents that inhibit these oncogenic pathways.

PMID- 22661392
TI  - An examination of suicide attempts among incarcerated sex offenders.
AB  - Little is known about suicide attempts among sex offenders. This study examines
      the rates of nonfatal suicide attempts among a sample (N = 3,030) of incarcerated
      male sex offenders. Overall, the authors found that 14% of sex offenders in the
      study sample had made a suicide attempt at some point in their lives. Of those,
      11% had reported a suicide attempt prior to incarceration, 0.5% had made a
      suicide attempt while incarcerated, and 2.5% made suicide attempts both prior to
      and during incarceration. Sex offenders who made suicide attempts were
      significantly more likely than those who did not make suicide attempts to have
      had an abusive childhood, a history of psychiatric problems, intellectual
      impairment, male victims, and related victims. Suicide attempters also scored
      higher on actuarial risk measures than nonattempters. No differences were found
      in attempter status between sex offenders who committed sex offenses against
      children and those who committed sex offenses against adults. A history of
      psychiatric problems and treatment as well as childhood abuse/neglect and
      perpetration against male victims predicted suicide attempter status. These
      findings are discussed as they pertain to suicide prevention, risk assessment,
      and the collateral consequences of sex offender legislation.

PMID- 22661393
TI  - Managing diabetes in patients with diabetes of long duration.
AB  - PURPOSE: The purpose of this article is to review clinical issues related to the
      management of hyperglycemia in older patients with diabetes of long duration.
      CONCLUSION: Older adults represent an extensive proportion of patients with type
      2 diabetes. Treatment goals need to be individualized to take into account
      comorbid conditions, life expectancy, diabetes complications, and the benefits of
      glycemic control. For both older patients and especially those with chronic renal
      insufficiency, the most important drug-related adverse effect to avoid is
      hypoglycemia, and avoidance of any severe hypoglycemia should be paramount.
      Patients with long duration of diabetes are often treated with insulin. Recent
      data show that glucagon-like peptide-1 receptor agonists may be used in
      combination with insulin for patients not achieving glycemic goals, with
      reductions in the doses of insulin used and with a low risk of hypoglycemia and
      possible weight loss.

PMID- 22661394
TI  - Parasitology of five primates in Mahale Mountains National Park, Tanzania.
AB  - Parasitological surveillance in primates has been performed using coprological
      observation and identification of specimens from chimpanzees (Pan troglodytes
      schweinfurthii) in Mahale Mountains National Park, Tanzania (Mahale). In this
      study, we conducted coprological surveillance to identify the fauna of parasite
      infection in five primate species in Mahale: red colobus (Procolobus badius
      tephrosceles), red-tailed monkeys (Cercopithecus ascanius schmidti), vervet
      monkeys (Cercopithecus aethiops pygerythrus), yellow baboons (Papio
      cynocephalus), and chimpanzees. Fecal samples were examined microscopically, and
      parasite identification was based on the morphology of cysts, eggs, larvae, and
      adult worms. Three nematodes (Oesophagostomum spp., Strongyloides sp., and
      Trichuris sp.), Entamoeba coli, and Entamoeba spp. were found in all five primate
      species. The following infections were identified: Bertiella studeri was found in
      chimpanzees and yellow baboons; Balantidium coli was found in yellow baboons;
      three nematodes (Streptopharagus, Primasubulura, an undetermined genus of
      Spirurina) and Dicrocoeliidae gen. sp. were found in red-tailed monkeys, vervet
      monkeys, and yellow baboons; Chitwoodspirura sp. was newly identified in red
      colobus and red-tailed monkeys; Probstmayria gombensis and Troglocorys cava were
      newly identified in chimpanzees, together with Troglodytella abrassarti; and
      Enterobius sp. was newly identified in red colobus. The parasitological data
      reported for red colobus, vervet monkeys, and yellow baboons in Mahale are the
      first reports for these species.

PMID- 22661395
TI  - Perceptual simulations can be as expressive as first-order logic.
AB  - Theories asserting that human reasoning is based on perceptual simulations often
      suppose these simulations are of concrete individual objects and the specific
      relations that hold among them. However, much human knowledge involves assertions
      about which relations do not hold, generalities over large numbers of objects and
      conditional facts. Can simulation theories explain how the mind represents these
      forms of knowledge, or are they inferior in their expressive power to knowledge
      representation schemes based on logical formalisms designed specifically to deal
      with negative, conditional and quantificational knowledge? In this paper, we show
      how assertions about mental simulations can in fact straightforwardly express all
      the concepts that comprise first-order logic, including negation, conditionals
      and both universal and existential quantification. We also speculate on how to
      extend this approach to deal with probabilistic and more expressive logics.

PMID- 22661396
TI  - Clinical features and diagnostic significance of the intraocular fluid of 217
      patients with intraocular lymphoma.
AB  - PURPOSE: Intraocular lymphoma is a rare disease with a poor prognosis. Early
      diagnosis and early treatment greatly influence the survival prognosis of this
      disease. This retrospective study aimed to clarify the clinical features of
      patients diagnosed with intraocular lymphoma, and the diagnostic significance of
      results from analysis of vitreous samples including cytology, cytokine
      measurements, and the IgH gene rearrangement test. METHODS: We reviewed 217
      patients with intraocular lymphoma diagnosed at 25 medical institutions in Japan.
      Together with clinical observation, cytological analysis, determination of the
      levels of cytokines, and/or detection of IgH gene rearrangements were conducted
      using vitreous fluid specimens. The results were studied in conjunction with
      clinical findings of intraocular lymphoma. Survival curves were estimated by use
      of the Kaplan-Meier method. RESULTS: The subjects comprised 85 men and 132 women,
      with a mean age at first ophthalmological examination of 63.4 years. The mean
      observation period was 41.3 months. During the observation period, 69 patients
      had onset of lymphoma in one eye and 148 had onset in both eyes. Intraocular
      lymphoma with involvement of the central nervous system (CNS) was most common,
      found in 60.8 % of the patients, whereas intraocular lymphoma without involvement
      of other organs was found in 28.1 % of patients. With respect to onset patterns,
      82.5 % of patients developed primary ocular lesions whereas 16.1 % developed
      primary CNS lesions preceding intraocular lymphoma. Blurred vision and ataxia
      were the most common ocular and extra-ocular symptoms that prompted patients to
      seek medical examination. Vitreous opacification was the most common ocular
      finding. The detection rates of malignant cytology, IL-10/IL-6 ratio greater than
      1.0, and IgH gene rearrangements in vitreous specimens were 44.5, 91.7, and 80.6
      %, respectively, of patients tested. IL-10/IL-6 ratio greater than 1.0 had the
      highest overall detection rate, and was extremely high (>=90 %) in patients with
      or without vitreous opacification. The 5-year survival rate was 61.1 %.
      CONCLUSION: Cytokine analysis of vitreous biopsy had the highest detection rate
      for intraocular lymphoma. This supplementary diagnostic test should be performed
      frequently to confirm a diagnosis of intraocular lymphoma.

PMID- 22661397
TI  - Risk factors for primary open-angle glaucoma in South Korea: the Namil study.
AB  - PURPOSE: To investigate the risk factors for primary open-angle glaucoma (POAG)
      in the Namil study population. METHODS: A cross-sectional, population-based
      epidemiological study of residents aged >=40 years from Namil-myon, South Korea,
      was conducted. Fifty-five subjects with POAG and 1,409 controls were enrolled in
      this study. Univariate and multivariate logistic regression analyses were
      performed to identify ocular and systemic factors associated with POAG. RESULTS:
      Multivariate logistic regression analysis demonstrated that older age, a history
      of thyroid disease and higher IOP were associated with an increased risk of POAG.
      Subgroup analysis showed that older age (OR 1.033, 95 % CI 1.003-1.063 per year),
      a history of thyroid disease (OR 7.373, 95 % CI 1.407-38.636) and higher IOP (OR
      1.132, 95 % CI 1.011-1.268 per mmHg) were risk factors for normal tension
      glaucoma (NTG, POAG with IOP <=21 mmHg). CONCLUSIONS: In the Namil study, higher
      IOP, older age and a history of thyroid disease were significant risk factors for
      POAG.

PMID- 22661398
TI  - Oxidative stress and tissue pathology caused by subacute exposure to ammonium
      acetate in rats and their response to treatments with alpha-ketoglutarate and N
      acetyl cysteine.
AB  - Ammonia is a widely used industrial chemical that is recognized as a potent
      neurotoxin and environmental pollutant. The present study addresses the oxidative
      stress and tissue pathology caused by 4 weeks of exposure to ammonium acetate
      (AMA; 100 mg/kg daily; orally) in rats, and their response to oral treatments
      with alpha-ketoglutarate (A-KG; 1.0 g/kg), a potential cyanide antidote, and/or N
      acetyl cysteine (NAC; 10 mg/kg), an antioxidant. The organ-body weight index of
      brain and liver was significantly increased by AMA but kidney was unaffected.
      Also, plasma ammonia levels were significantly elevated without any concomitant
      change in blood gas status and hematology but levels of catalase, superoxide
      dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione
      (GSH) in the brain and liver were diminished, accompanied by elevated levels of
      malondialdehyde. Levels of glutathione disulfide (GSSG) were unaffected, but the
      ratio of GSH:GSSG was reduced. Plasma alkaline phosphatase, alanine
      aminotransferase, aspartate aminotransferase and total bilirubin were raised but
      urea, uric acid and creatinine levels were not altered. AMA also caused temporal,
      hepatic and renal pathology. However, the renal pathology was not supported by
      any biochemical alterations. A-KG or NAC alone afforded less protection against
      AMA as compared to both given together. The protective efficacy of A-KG can be
      ascribed to its ability to detoxify ammonia and additionally both A-KG and NAC
      have antioxidant properties as well. The study suggests a new therapeutic regimen
      for ammonia poisoning. 

PMID- 22661399
TI  - The protective effects of carnosine in alcohol-induced hepatic injury in rats.
AB  - Consumption of alcohol leads to oxidative stress in liver by inducing lipid
      peroxidation. The aim of this study was to investigate the effects of carnosine
      (CAR) in alcohol-induced liver injury by biochemical and histomorphological
      evaluations. The rats were divided into four groups, namely, control group,
      alcohol (AL) group, CAR group and AL + CAR group. Three doses of ethanol (5 g/kg,
      25% (v/v) in distilled water) were given by nasogastric catheter for twice-a-day.
      CAR (100 mg/kg) was given 1 h before the administration of ethanol using the same
      method. Levels of alanine aminotransferase, aspartate aminotransferase,
      myeloperoxidase and malondialdehyde were significantly increased in the AL group
      compared with control, CAR and AL + CAR groups. Glutathione level was
      significantly decreased in the AL group, while it was increased in the AL + CAR
      group. Immunoreactivity of caspase-3 and bax increased in the hepatocytes of AL
      group when compared with control and AL + CAR groups. Expression of bcl-2 was
      decreased in AL group than AL + CAR group. Under electron microscopy, dense
      mitochondria, accumulation of lipid, sinusoidal dilatation, vacuolization and
      decrease in the number of microvilli were observed in AL group, while these
      findings were markedly less in the AL + CAR group. In conclusion, pretreatment of
      CAR is effective for recovering biochemical alterations and morphologic damage in
      the liver of rats treated with ethanol. 

PMID- 22661400
TI  - Interleukin-18, interleukin-8, and CXCR2 and the risk of silicosis.
AB  - Molecular mechanisms in the pathogenesis of silicosis are not fully understood.
      Exposure to crystalline silica leads to the activation of signaling pathways
      controlling the production and secretion of inflammatory mediators. Inflammatory
      cytokines are noted as important candidate genes for fibrotic lung diseases.
      Cytokines, chemokines, and variations of their genes have been associated with
      upregulation or downregulation of chronic inflammatory mediators. Variations in
      the interleukin (IL)-18, IL-8 and chemokine receptor CXCR2 genes are believed to
      influence the risk of silicosis in stone-grinding factory workers in Iran. Allele
      specific oligonucleotide polymerase chain reaction (PCR) procedure was carried
      out for IL-18 -137 and IL-18 -607, meanwhile touchdown PCR was performed for IL-8
      -251 and CXCR2 +1208 genotyping. Variation in genotypic and allelic frequencies
      was not statistically different among cases versus controls (p > 0.05). These
      findings indicated for the first time that IL-18 -137, IL-18 -607, IL-8 -251, and
      CXCR2 +1208 are suggested not to influence the risk of silicosis in tested
      occupational group. 

PMID- 22661401
TI  - Bioremoval of heavy metals from industrial effluent by fixed-bed column of red
      macroalgae.
AB  - Three different species of nonliving red algal biomass Laurancia obtusa,
      Geldiella acerosa and Hypnea sp. were used to build three types of fixed-bed
      column for the removal of toxic heavy metal ions such as Cu(2+), Zn(2+), Mn(2+)
      and Ni(2+) from industrial effluent. In general, the highest efficiency of metal
      ion bioremoval was recorded for algal column of L. obtusa followed by G. acerosa
      and the lowest one was recorded for Hypnea sp., with mean removal values of 94%,
      85% and 71%, respectively. The obtained results showed that biological treatments
      of industrial effluents with these algal columns, using standard algal biotest,
      Pseudokirchneriella subcapitata, were capable of reducing effluent toxicities
      from 75% to 15%, respectively. Red algal column may be considered as an
      inexpensive and efficient alternative treatment for conventional removal
      technology, for sequestering heavy metal ions from industrial effluents.

PMID- 22661402
TI  - Role of aqueous Bryoria capillaris (Ach.) extract as a genoprotective agent on
      imazalil-induced genotoxicity in vitro.
AB  - In recent years, a number of studies have suggested that lichens might be the
      easily accessible sources of natural drugs that could be used as a possible food
      supplement. Extensive research is being carried out to explore the importance of
      lichen species, which are known to contain a variety of pharmacological active
      compounds. On the other hand, imazalil (IMA), a commonly used fungicide in both
      agricultural and clinical domains, is suspected to produce very serious toxic
      effects in vertebrates. In this context, the antigenotoxic effect of aqueous
      Bryoria capillaris (Ach.) extract (BCE) was studied against the genotoxic damage
      induced by IMA on cultured human lymphocytes using chromosomal aberrations (CA)
      and micronucleus (MN) as cytogenetic parameters. Human peripheral lymphocytes
      were treated in vitro with varying concentrations of BCE (5, 10, 25, 50 and 100
      ug/mL), tested in combination with IMA (336 ug/mL). BCE alone was not genotoxic,
      and when combined with IMA treatment, it reduced the frequency of CAs and the
      rates of MN. A clear dose-dependent decrease in the genotoxic damage of IMA was
      observed, suggesting a genoprotective role of BCE. The results of the present
      study suggest that this plant extract per se do not have genotoxic potential, but
      can modulate the genotoxicity of IMA on peripheral human lymphocytes in vitro. In
      conclusion, our findings may have an important application in the protection of
      cultured human lymphocyte from the genetic damage and side effects induced by
      agricultural and medical chemicals that are hazardous to people. 

PMID- 22661403
TI  - Behavioral detection of passive whisker stimuli requires somatosensory cortex.
AB  - Rodent whisker sensation occurs both actively, as whiskers move rhythmically
      across objects, and in a passive mode in which externally applied deflections are
      sensed by static, non-moving whiskers. Passive whisker stimuli are robustly
      encoded in the somatosensory (S1) cortex, and provide a potentially powerful
      means of studying cortical processing. However, whether S1 contributes to passive
      sensation is debated. We developed 2 new behavioral tasks to assay passive
      whisker sensation in freely moving rats: Detection of unilateral whisker
      deflections and discrimination of right versus left whisker deflections. Stimuli
      were simple, simultaneous multi-whisker deflections. Local muscimol inactivation
      of S1 reversibly and robustly abolished sensory performance on these tasks. Thus,
      S1 is required for the detection and discrimination of simple stimuli by passive
      whiskers, in addition to its known role in active whisker sensation.

PMID- 22661404
TI  - Perseveration and choice in Parkinson's disease: the impact of progressive
      frontostriatal dysfunction on action decisions.
AB  - We have previously shown that patients with Parkinson's disease (PD) perseverate
      in their choice of action relative to healthy controls, and that this is affected
      by dopaminergic medication (Hughes LE, Barker RA, Owen AM, Rowe JB. 2010.
      Parkinson's disease and healthy aging: Independent and interacting effects on
      action selection. Hum Brain Mapp. 31:1886-1899). To understand further the neural
      basis of these phenomena, we used a new task that manipulated the options to
      repeat responses. Seventeen patients with idiopathic PD were studied both "on"
      and "off" dopaminergic medication and 18 healthy adults were scanned twice as
      controls. All subjects performed a right-handed 3-choice button press task, which
      controlled the availability of repeatable responses. The frequency of choosing to
      repeat a response (a form of perseveration) in patients was related to dopamine
      therapy and disease severity as a "U-shaped" function. For repetitive trials,
      this "U-shaped" relationship was also reflected in the BOLD response in the
      caudate nuclei and ventrolateral prefrontal cortex. Our results support a U
      shaped model of optimized cortico-striatal circuit function and clearly
      demonstrate that flexibility in response choice is modulated by an interaction of
      dopamine and disease severity.

PMID- 22661405
TI  - The role of interneuron networks in driving human motor cortical plasticity.
AB  - The after-effects of repetitive transcranial magnetic stimulation (rTMS) are
      highly variable between individuals. Because different populations of cortical
      neurons are stimulated more easily or are more excitable in different people at
      different times, the variability may not be due to differences between
      individuals in the plasticity of cortical synapses, but may instead be due to
      individual differences in the recruitment of cortical neurons. In this study, we
      examined the effects of rTMS in 56 healthy volunteers. The responses to
      excitatory and inhibitory theta burst stimulation (TBS) protocols were highly
      variable between individuals. Surprisingly, the TBS effect was highly correlated
      with the latency of motor-evoked potentials (MEPs) evoked by TMS pulses that
      induced an anterior-posterior (AP) directed current across the central sulcus.
      Finally, we devised a new plasticity protocol using closely timed pairs of
      oppositely directed TMS current pulses across the central sulcus. Again, the
      after-effects were related to the latency of MEPs evoked by AP current. Our
      results are consistent with the idea that variation in response to rTMS
      plasticity probing protocols is strongly influenced by which interneuron networks
      are recruited by the TMS pulse.

PMID- 22661406
TI  - Effects of age, task performance, and structural brain development on face
      processing.
AB  - In this combined structural and functional MRI developmental study, we tested 48
      participants aged 7-37 years on 3 simple face-processing tasks (identity,
      expression, and gaze task), which were designed to yield very similar performance
      levels across the entire age range. The same participants then carried out 3 more
      difficult out-of-scanner tasks, which provided in-depth measures of changes in
      performance. For our analysis we adopted a novel, systematic approach that
      allowed us to differentiate age- from performance-related changes in the BOLD
      response in the 3 tasks, and compared these effects to concomitant changes in
      brain structure. The processing of all face aspects activated the core face
      network across the age range, as well as additional and partially separable
      regions. Small task-specific activations in posterior regions were found to
      increase with age and were distinct from more widespread activations that varied
      as a function of individual task performance (but not of age). Our results
      demonstrate that activity during face-processing changes with age, and these
      effects are still observed when controlling for changes associated with
      differences in task performance. Moreover, we found that changes in white and
      gray matter volume were associated with changes in activation with age and
      performance in the out-of-scanner tasks.

PMID- 22661407
TI  - Toward the neural mechanisms of reduced working memory capacity in schizophrenia.
AB  - People with schizophrenia (PSZ) demonstrate reliable reductions in working memory
      (WM) capacity (i.e., the number of objects that can be held in memory). The
      present study asked whether WM impairments in PSZ can be explained by the same
      neural mechanisms that underlie individual differences in WM capacity among
      healthy individuals. Specifically, we examined event-related potentials in PSZ
      and healthy matched controls during a change detection task that required the
      storage of multiple objects in WM. The amplitude of contralateral delay activity
      (CDA), which correlates with WM capacity in healthy individuals, was larger in
      controls than in PSZ for memory loads of 3 and 5 objects, but larger in PSZ than
      in controls for a memory load of 1. This same pattern was found in the subgroups
      of PSZ and controls with an equivalent WM capacity. Moreover, the increase in CDA
      amplitude was correlated with individual differences in capacity in controls, but
      not in PSZ. These results demonstrate that WM impairment in PSZ is not associated
      with the same patterns of neural activity that characterize low WM capacity in
      healthy individuals. We propose that WM impairment in PSZ instead reflects a
      specific impairment in the ability to distribute attention broadly.

PMID- 22661409
TI  - Functional neural plasticity and associated changes in positive affect after
      compassion training.
AB  - The development of social emotions such as compassion is crucial for successful
      social interactions as well as for the maintenance of mental and physical health,
      especially when confronted with distressing life events. Yet, the neural
      mechanisms supporting the training of these emotions are poorly understood. To
      study affective plasticity in healthy adults, we measured functional neural and
      subjective responses to witnessing the distress of others in a newly developed
      task (Socio-affective Video Task). Participants' initial empathic responses to
      the task were accompanied by negative affect and activations in the anterior
      insula and anterior medial cingulate cortex--a core neural network underlying
      empathy for pain. Whereas participants reacted with negative affect before
      training, compassion training increased positive affective experiences, even in
      response to witnessing others in distress. On the neural level, we observed that,
      compared with a memory control group, compassion training elicited activity in a
      neural network including the medial orbitofrontal cortex, putamen, pallidum, and
      ventral tegmental area--brain regions previously associated with positive affect
      and affiliation. Taken together, these findings suggest that the deliberate
      cultivation of compassion offers a new coping strategy that fosters positive
      affect even when confronted with the distress of others.

PMID- 22661410
TI  - Disrupting pre-SMA activity impairs facial happiness recognition: an event
      related TMS study.
AB  - It has been suggested that the left pre-supplementary motor area (pre-SMA) could
      be implicated in facial emotion expression and recognition, especially for
      laughter/happiness. To test this hypothesis, in a single-blind, randomized
      crossover study, we investigated the impact of transcranial magnetic stimulation
      (TMS) on performances of 18 healthy participants during a facial emotion
      recognition task. Using a neuronavigation system based on T1-weighted magnetic
      resonance imaging of each participant, TMS (5 pulses, 10 Hz) was delivered over
      the pre-SMA or the vertex (control condition) in an event-related fashion after
      the presentation of happy, fear, and angry faces. Compared with performances
      during vertex stimulation, we observed that TMS applied over the left pre-SMA
      specifically disrupted facial happiness recognition (FHR). No difference was
      observed between the 2 conditions neither for fear and anger recognition nor for
      reaction times (RT). Thus, interfering with pre-SMA activity with event-related
      TMS after stimulus presentation produced a selective impairment in the
      recognition of happy faces. These findings provide new insights into the
      functional implication of the pre-SMA in FHR, which may rely on the mirror
      properties of pre-SMA neurons.

PMID- 22661411
TI  - The influence of prior expectations on emotional face perception in adolescence.
AB  - Prior expectations influence the way incoming stimuli are processed. A standard,
      validated way of manipulating prior expectations is to bias participants to
      perceive a stimulus by instructing them to look out for this type of stimulus.
      Here, we investigated the influence of prior expectations on the processing of
      incoming stimuli (emotional faces) in adolescence. Using functional magnetic
      resonance imaging, we assessed activity and functional connectivity in 13
      adolescents and 13 healthy adults (matched for gender and intelligence quotient),
      while they were presented with sequences of emotional faces (happy, fearful, or
      angry). A specific instruction at the start of each sequence instructed the
      participants to look out for fearful or angry faces in the subsequent sequence.
      Both groups responded more accurately and with shorter reaction times (RTs) to
      faces that were congruent with the instruction. For anger, this bias was lower in
      the adolescents (for RTs), and adults demonstrated greater activation than
      adolescents in the ventro-medial prefrontal cortex (vMPFC) and greater functional
      connectivity between the vMPFC and the thalamus when the face was congruent with
      the instruction. Our results demonstrate that the influence of prior expectations
      (in the form of an instruction) on the subsequent processing of face stimuli is
      still developing in the adolescent brain.

PMID- 22661408
TI  - Impaired language pathways in tuberous sclerosis complex patients with autism
      spectrum disorders.
AB  - The purpose of this study was to examine the relationship between language
      pathways and autism spectrum disorders (ASDs) in patients with tuberous sclerosis
      complex (TSC). An advanced diffusion-weighted magnetic resonance imaging (MRI)
      was performed on 42 patients with TSC and 42 age-matched controls. Using a
      validated automatic method, white matter language pathways were identified and
      microstructural characteristics were extracted, including fractional anisotropy
      (FA) and mean diffusivity (MD). Among 42 patients with TSC, 12 had ASD (29%).
      After controlling for age, TSC patients without ASD had a lower FA than controls
      in the arcuate fasciculus (AF); TSC patients with ASD had even a smaller FA,
      lower than the FA for those without ASD. Similarly, TSC patients without ASD had
      a greater MD than controls in the AF; TSC patients with ASD had even a higher MD,
      greater than the MD in those without ASD. It remains unclear why some patients
      with TSC develop ASD, while others have better language and socio-behavioral
      outcomes. Our results suggest that language pathway microstructure may serve as a
      marker of the risk of ASD in TSC patients. Impaired microstructure in language
      pathways of TSC patients may indicate the development of ASD, although
      prospective studies of language pathway development and ASD diagnosis in TSC
      remain essential.

PMID- 22661414
TI  - Training in capillaroscopy: a growing interest.

PMID- 22661412
TI  - Robo1 regulates the migration and laminar distribution of upper-layer pyramidal
      neurons of the cerebral cortex.
AB  - Laminar organization is a key feature of the mammalian cerebral cortex, but the
      mechanisms by which final positioning and "inside-out" distribution of neurons
      are determined remain largely unknown. Here, we demonstrate that Robo1, a member
      of the family of Roundabout receptors, regulates the correct positioning of
      layers II/III pyramidal neurons in the neocortex. Specifically, we used RNA
      interference in mice to suppress the expression of Robo1 in a subset of layers
      II/III neurons, and observed the positions of these cells at distinct
      developmental stages. In contrast to control neurons that migrated toward the
      pial surface by P1, Robo1-suppressed neurons exhibited a delay in entering the
      cortical plate at respective stages. Unexpectedly, after the first postnatal
      week, these neurons were predominantly located in the upper part of layers
      II/III, in contrast to control cells that were distributed throughout these
      layers. Sequential electroporation studies revealed that Robo1-suppressed cells
      failed to establish the characteristic inside-out neuronal distribution and,
      instead, they accumulated beneath the marginal zone regardless of their
      birthdate. These results demonstrate that Robo receptors play a crucial role in
      neocortical lamination and particularly in the positioning of layers II/III
      pyramidal neurons.

PMID- 22661415
TI  - The salivary gland epithelial cell in Sjogren's Syndrome: what are the steps
      involved in wounding or killing their secretory function?

PMID- 22661413
TI  - Demonstration of tuning to stimulus orientation in the human visual cortex: a
      high-resolution fMRI study with a novel continuous and periodic stimulation
      paradigm.
AB  - Cells in the animal early visual cortex are sensitive to contour orientations and
      form repeated structures known as orientation columns. At the behavioral level,
      there exist 2 well-known global biases in orientation perception (oblique effect
      and radial bias) in both animals and humans. However, their neural bases are
      still under debate. To unveil how these behavioral biases are achieved in the
      early visual cortex, we conducted high-resolution functional magnetic resonance
      imaging experiments with a novel continuous and periodic stimulation paradigm. By
      inserting resting recovery periods between successive stimulation periods and
      introducing a pair of orthogonal stimulation conditions that differed by 90
      degrees  continuously, we focused on analyzing a blood oxygenation level
      dependent response modulated by the change in stimulus orientation and reliably
      extracted orientation preferences of single voxels. We found that there are more
      voxels preferring horizontal and vertical orientations, a physiological substrate
      underlying the oblique effect, and that these over-representations of horizontal
      and vertical orientations are prevalent in the cortical regions near the
      horizontal- and vertical-meridian representations, a phenomenon related to the
      radial bias. Behaviorally, we also confirmed that there exists perceptual
      superiority for horizontal and vertical orientations around horizontal and
      vertical meridians, respectively. Our results, thus, refined the neural
      mechanisms of these 2 global biases in orientation perception.

PMID- 22661416
TI  - Arteriosclerosis of whole aorta in takayasu arteritis.

PMID- 22661417
TI  - Do low titers of antibody against hepatitis B surface antigen carry a risk of
      viral reactivation during immunosuppressive therapy for rheumatic diseases?

PMID- 22661418
TI  - Purpose and significance of the 2010 criteria and modification of the 2010
      criteria for fibromyalgia.

PMID- 22661419
TI  - Is tocilizumab an effective option for treatment of refractory uveitis associated
      with juvenile idiopathic arthritis?

PMID- 22661420
TI  - Should rheumatologists palpate the breast?

PMID- 22661421
TI  - Use of hydroxychloroquine in Japan.

PMID- 22661422
TI  - Miliary tuberculosis following negative latent tuberculosis infection screening
      prior to tumor necrosis factor-alpha antagonists: implications for management?

PMID- 22661423
TI  - Progressive multifocal leukoencephalopathy in a patient with polymyositis: case
      report and literature review.

PMID- 22661425
TI  - Lichen planus in association with adult-onset still's disease successfully
      treated with mycophenolate mofetil.

PMID- 22661424
TI  - Atypical psoriasis following rituximab for rheumatoid arthritis.

PMID- 22661426
TI  - Enhanced healing of sacral and pubic insufficiency fractures by teriparatide.

PMID- 22661427
TI  - Rare case of septic arthritis caused by Candida krusei: case report and
      literature review.

PMID- 22661428
TI  - Discovery of O-GlcNAc-modified proteins in published large-scale proteome data.
AB  - The attachment of N-acetylglucosamine to serine or threonine residues (O-GlcNAc)
      is a post-translational modification on nuclear and cytoplasmic proteins with
      emerging roles in numerous cellular processes, such as signal transduction,
      transcription, and translation. It is further presumed that O-GlcNAc can exhibit
      a site-specific, dynamic and possibly functional interplay with phosphorylation.
      O-GlcNAc proteins are commonly identified by tandem mass spectrometry following
      some form of biochemical enrichment. In the present study, we assessed if, and to
      which extent, O-GlcNAc-modified proteins can be discovered from existing large
      scale proteome data sets. To this end, we conceived a straightforward O-GlcNAc
      identification strategy based on our recently developed Oscore software that
      automatically analyzes tandem mass spectra for the presence and intensity of O
      GlcNAc diagnostic fragment ions. Using the Oscore, we discovered hundreds of O
      GlcNAc peptides not initially identified in these studies, and most of which have
      not been described before. Merely re-searching this data extended the number of
      known O-GlcNAc proteins by almost 100 suggesting that this modification exists
      even more widely than previously anticipated and the modification is often
      sufficiently abundant to be detected without enrichment. However, a comparison of
      O-GlcNAc and phospho-identifications from the very same data indicates that the O
      GlcNAc modification is considerably less abundant than phosphorylation. The
      discovery of numerous doubly modified peptides (i.e. peptides with one or
      multiple O-GlcNAc or phosphate moieties), suggests that O-GlcNAc and
      phosphorylation are not necessarily mutually exclusive, but can occur
      simultaneously at adjacent sites.

PMID- 22661429
TI  - The polarized total internal reflection fluorescence microscopy (polTIRFM)
      twirling filament assay.
AB  - Polarized total internal reflection fluorescence microscopy (polTIRFM) can be
      used to detect the spatial orientation and rotational dynamics of single
      molecules. polTIRFM determines the three-dimensional angular orientation and the
      extent of wobble of a fluorescent probe bound to the macromolecule of interest.
      This protocol describes the twirling filament assay, so named because actin
      sometimes twirls about its own axis as it is translocated by myosin. A gliding
      filament assay is constructed in which a sparsely labeled actin filament (0.3% of
      the actin monomers contain 6'- iodoacetamidotetramethylrhodamine [IATR]) is
      translocated by a field of unlabeled myosin V fixed to the surface. The polTIRFM
      twirling assay differs from a standard gliding filament assay in that full
      filaments are not visible, but rather individual fluorophores are spaced along
      each filament. The goal is to investigate possible rotational motions of the
      actin filament about its axis (i.e., twirling) by measuring the spatial angle of
      the fluorescent probe as a function of time. Successful assays contain
      microscopic fields of approximately 50 isolated points of fluorescence that move
      across the field in the presence of ATP. Actin is usually translocated by more
      than one myosin molecule, depending on the filament length and the myosin surface
      density. Sparsely labeled filaments are required because the orientation of only
      one probe can be resolved at a time.

PMID- 22661430
TI  - The acquisition and analysis of polarized total internal reflection fluorescence
      microscopy (polTIRFM) data.
AB  - Polarized total internal reflection fluorescence microscopy (polTIRFM) can be
      used to detect the spatial orientation and rotational dynamics of single
      molecules. polTIRFM determines the three-dimensional angular orientation and the
      extent of wobble of a fluorescent probe bound to the macromolecule of interest.
      This protocol describes how to acquire polTIRFM data and then calibrate the
      setup. Calibration corrects for any systematic variations in beam intensity and
      unequal detector sensitivities and is performed for each slide after experimental
      data are recorded. To convert the intensities into angles, one set of (theta,
      phi, delta(s), delta(f), kappa) is then determined from one complete cycle of the
      incident intensities. This process is repeated for every cycle in the trace to
      measure the time dependence of rotational motions. The collection and analysis of
      data is similar for the processive motility assay for myosin V and for the
      twirling filament assay, in which a sparsely labeled actin filament is
      translocated by a field of unlabeled myosin V.

PMID- 22661431
TI  - A colony-forming assay for determining the establishment efficiency of S/MAR
      containing nonviral episomal expression vectors.
AB  - As with all eukaryotic replicons, the stable establishment of S/MAR
      (scaffold/matrix attached region) vectors is a stochastic event that depends on
      poorly understood epigenetic factors such as chromatin structure and nuclear
      localization. Establishment efficiency describes the percentage of cells in which
      a particular S/MAR vector is stably retained as an episome after an initial
      selection period. Expected establishment efficiency for S/MAR vectors is 1-5%.
      This article describes a colony-forming assay that may be used either to
      determine establishment efficiency or to generate single cell clones.

PMID- 22661432
TI  - Rescue of S/MAR-containing nonviral episomal expression vectors.
AB  - The episomal status of S/MAR (scaffold/matrix attached region)-based vectors can
      be confirmed by several methods including Southern blots, fluorescence in situ
      hybridization (FISH) analysis, or plasmid rescue experiments. In rescue
      experiments, genomic DNA (gDNA) or DNA from Hirt extracts is isolated from cell
      clones or mixed populations in which S/MAR plasmids are stably established.
      Bacteria are transformed with this DNA and if episomal plasmid DNA (pDNA) is
      present, resistant bacterial colonies will form.

PMID- 22661433
TI  - Electroporation and use of hepatitis B virus envelope L proteins as
      bionanocapsules.
AB  - Hepatitis B virus (HBV) envelope L proteins, when synthesized in yeast cells,
      form a hollow bionanocapsule (BNC) in which genes (including large plasmids up to
      40 kbp), small interfering RNA (siRNA), drugs, and proteins can be enclosed by
      electroporation. BNCs made from L proteins have several advantages as a delivery
      system: Because they display a human liver-specific receptor (the pre-S region of
      the L protein) on their surface, BNCs can efficiently and specifically deliver
      their contents to human liver-derived cells and tissues ex vivo (in cell culture)
      and in vivo (in a mouse xenograft model). Retargeting can be achieved simply by
      substituting other biorecognition molecules such as antibodies, ligands,
      receptors, and homing peptides for the pre-S region. In addition, BNCs have
      already been proven to be safe for use in humans during their development as an
      immunogen of hepatitis B vaccine. This protocol describes the loading of BNCs and
      their use in cell culture and in vivo.

PMID- 22661434
TI  - Power calculations in genetic studies.
AB  - The power of a statistical test is the probability that it will yield a
      statistically significant result given that the null hypothesis is false. In
      other words, it represents the chance that the study will be successful in
      detecting a true effect and is dependent on a number of factors, including the
      magnitude of the effect, the sample size and study design, and the specified
      false-positive rate. Power calculations are primarily performed during the
      planning stages of a study, most typically in determining the sample size
      required. Consideration of statistical power can also sometimes shed light on the
      results of completed studies, particularly in the interpretation of negative
      results. In this article, we review the fundamentals of statistical power,
      discuss how power is calculated (using a genetic case/control study as an
      example), and consider the most pertinent factors that influence power in genetic
      studies. Finally, we focus on power in the context of modern whole-genome
      association studies, in which issues of coverage, multiple testing, and staged
      designs are paramount.

PMID- 22661435
TI  - Episcopic three-dimensional imaging of embryos.
AB  - Episcopic fluorescence image capturing (EFIC) and high-resolution episcopic
      microscopy (HREM) are related techniques that are used to generate digital volume
      data and create three-dimensional (3D) images. Both techniques require specimens
      that are embedded in an appropriate medium, and images are captured from
      successive sections before removal from the embedded tissue block. EFIC detects
      autofluorescence emitted from the embedded tissue, whereas HREM requires the
      tissue to be stained with a fluorescent dye such as eosin. Different procedures
      are therefore necessary for embedding tissue for EFIC or HREM imaging. This
      article describes episcopic imaging and gives the advantages and disadvantages of
      the EFIC and HREM techniques. It also describes the imaging setup required to
      collect volume data and generate 3D images.

PMID- 22661436
TI  - Embedding embryos for episcopic fluorescence image capturing (EFIC).
AB  - Episcopic fluorescence image capturing (EFIC) and high-resolution episcopic
      microscopy (HREM) are related techniques that are used to generate digital volume
      data and create three-dimensional (3D) images. Both techniques require specimens
      that are embedded in an appropriate medium, and images are captured from
      successive sections before removal from the embedded tissue block. EFIC detects
      autofluorescence emitted from the embedded tissue, whereas HREM requires the
      tissue to be stained with a fluorescent dye such as eosin. Different procedures
      are therefore necessary for embedding tissue for EFIC or HREM imaging. This
      protocol describes the procedure for embedding E11.5 mouse embryos for EFIC
      imaging. Processing times should be adapted for the size and nature of other
      specimens.

PMID- 22661437
TI  - Embedding embryos for high-resolution episcopic microscopy (HREM).
AB  - Episcopic fluorescence image capturing (EFIC) and high-resolution episcopic
      microscopy (HREM) are related techniques that are used to generate digital volume
      data and create three-dimensional (3D) images. Both techniques require specimens
      that are embedded in an appropriate medium, and images are captured from
      successive sections before removal from the embedded tissue block. EFIC detects
      autofluorescence emitted from the embedded tissue, whereas HREM requires the
      tissue to be stained with a fluorescent dye such as eosin. Different procedures
      are therefore necessary for embedding tissue for EFIC or HREM imaging. For HREM,
      the choice of fixative appears to be of little consequence. If gene expression
      patterns are to be visualized in addition to tissue architecture, whole-mount
      staining for gene expression patterns using the 4-nitro blue tetrazolium chloride
      (NBT)/5-bromo-4-chloro-3-indolyl phosphate (BCIP) or LacZ detection system must
      be performed before embedding of samples. This protocol describes the procedure
      for embedding E11.5 mouse embryos for HREM imaging. Processing times should be
      adapted for the size and nature of other specimens.

PMID- 22661438
TI  - Generation of volume data by episcopic three-dimensional imaging of embryos.
AB  - Episcopic fluorescence image capturing (EFIC) and high-resolution episcopic
      microscopy (HREM) are related techniques that are used to generate digital volume
      data and create three-dimensional (3D) images. Both techniques require specimens
      that are embedded in an appropriate medium, and images are captured from
      successive sections before removal from the embedded tissue block. EFIC detects
      autofluorescence emitted from the embedded tissue, whereas HREM requires the
      tissue to be stained with a fluorescent dye such as eosin. Volume data are
      generated as the successive sections are imaged and removed using a microtome.
      This protocol describes the procedure for digital data processing, visualization,
      and archiving for both EFIC and HREM.

PMID- 22661439
TI  - Imaging neuronal activity with genetically encoded calcium indicators.
AB  - Genetically encoded calcium indicators (GECIs), which are based on chimeric
      fluorescent proteins, can be used to monitor calcium transients in living cells
      and organisms. Because they are encoded by DNA, GECIs can be delivered to the
      intact brain noninvasively and targeted to defined populations of neurons and
      specific subcellular compartments for long-term, repeated measurements in vivo.
      GECIs have improved iteratively and are becoming useful for imaging neural
      activity in vivo. Here we summarize extrinsic and intrinsic factors that
      influence a GECI's performance and provides guidelines for selecting the
      appropriate GECI for a given application. We also review recent progress in GECI
      design, optimization, and standardized testing protocols.

PMID- 22661440
TI  - Imaging neocortical neurons through a chronic cranial window.
AB  - The rich structural dynamics of axonal arbors and neuronal circuitry can only be
      revealed through direct and repeated observations of the same neuron(s) over
      time, preferably in vivo. This protocol describes a long-term, high-resolution
      method for imaging neocortical neurons in vivo, using a combination of two-photon
      laser scanning microscopy (2PLSM) and a surgically implanted chronic cranial
      window. The window is used because the skull of most mammals is too opaque to
      allow high-resolution imaging of cortical neurons. Using this method, it is
      feasible to image the smallest neuronal structures in the superficial layers of
      the neocortex, such as dendritic spines and axonal boutons. Because the surface
      area of the craniotomy is relatively large, this technique is even suitable for
      use when labeled neurons are relatively uncommon. The surgery and imaging
      procedures are illustrated with examples from our studies of structural
      plasticity in the developing or adult mouse brain. The protocol is optimized for
      adult mice; we have used mice up to postnatal day 511 (P511). With minor
      modifications, it is possible to image neurons in rats and mice from P2. Most of
      our studies have used the Thy1 promoter to drive expression of fluorophores in
      subsets of cortical neurons.

PMID- 22661441
TI  - Handling S/MAR vectors.
AB  - Nonviral episomal vectors represent attractive alternatives to currently used
      virus-based expression systems. In the late 1990s, it was shown that a plasmid
      containing an expression cassette linked to a scaffold/matrix attached region
      (S/MAR) replicates as a low copy number episome in all cell lines tested, as well
      as primary cells, and can be used for the genetic modification of higher animals.
      Once established in the cell, the S/MAR vector replicates early during S-phase
      and, in the absence of selection, is stably retained in the cells for an
      unlimited period of time. This vector can therefore be regarded as a minimal
      model system for studying the epigenetic regulation of replication and functional
      nuclear architecture. In theory, this construct represents an almost "ideal"
      expression system for gene therapy. In practice, S/MAR-based vectors stably
      modify mammalian cells with efficiencies far below those of virus-based
      constructs. Consequently, they have not yet found application in gene therapy
      trials. Furthermore, S/MAR vector systems are not trivial to handle and several
      critical technical issues have to be considered when modifying these vectors for
      various applications.

PMID- 22661442
TI  - Setup for functional cell ablation with lasers: coupling of a laser to a
      microscope.
AB  - The selective removal of cells by ablation is a powerful tool in the study of
      eukaryotic developmental biology, providing much information about their origin,
      fate, or function in the developing organism. In Drosophila, three main methods
      have been used to ablate cells: chemical, genetic, and laser ablation. Each
      method has its own applicability with regard to developmental stage and the cells
      to be ablated, and its own limitations. The primary advantage of laser-based
      ablation is the flexibility provided by the method: The operations can be
      performed in any cell pattern and at any time in development. Laser-based
      techniques permit manipulation of structures within cells, even to the molecular
      level. They can also be used for gene activation. However, laser ablation can be
      expensive, labor-intensive, and time-consuming. Although live cells can be
      difficult to image in Drosophila embryos, the use of vital fluorescent imaging
      methods has made laser-mediated cell manipulation methods more appealing; the
      methods are relatively straightforward. This article provides the information
      necessary for setting up and using a laser microscope for lasesr ablation
      studies.

PMID- 22661443
TI  - Embryonic cell ablation in Drosophila using lasers.
AB  - Cell ablation is a powerful tool in the study of eukaryotic developmental
      biology. The selective removal of cells by ablation may provide much information
      about their origin, fate, or function in the developing organism. Laser-based
      techniques have an advantage over genetic or chemical ablation methods in that
      the operations can be performed in essentially any cell pattern and at any time
      in development. This protocol describes the methods needed to target and ablate
      specific cells of interest in Drosophila embryos with lasers.

PMID- 22661444
TI  - Photoconversion for tracking the dynamics of cell movement in Xenopus laevis
      embryos.
AB  - Xenopus laevis is an ideal model system for investigating dynamic morphogenetic
      processes during embryogenesis, regeneration, and homeostasis. Our understanding
      of these events has been greatly facilitated by lineage labeling, that is,
      marking a cell or a group of cells and all their descendants using vital dyes,
      fluorescent molecules, or transplantation techniques. Unfortunately, these
      strategies are limited in their spatiotemporal resolution: They do not allow long
      term dynamic in vivo imaging, are generally invasive, and labeling is restricted
      to cells on the surface. Genetically encoded fluorescent proteins (FPs), on the
      other hand, provide excellent alternative methods to traditional lineage
      labeling, enabling labeling with high spatiotemporal resolution and tracking of
      cellular and subcellular structures to study patterning events. Over the past
      decade, FPs have evolved to allow fine control of their spectral properties (in a
      defined region of interest) for greater labeling specificity. One example is
      EosFP, which is a protein cloned from the scleractinian coral Lobophyllia
      hemprichii that can be photoconverted from green to red fluorescence state with
      near-ultraviolet (UV) light irradiation. Here, we describe EosFP-photoconversion
      of Xenopus embryos to track cells during developmental and regenerative processes
      using a metal-halide- or xenon-arc-based fluorescent microscope system, which
      provides a simpler, less expensive alternative to photoconversion using laser
      microscopy.

PMID- 22661446
TI  - The polarized total internal reflection fluorescence microscopy (polTIRFM)
      processive motility assay for myosin V.
AB  - Polarized total internal reflection fluorescence microscopy (polTIRFM) can be
      used to detect the spatial orientation and rotational dynamics of single
      molecules. polTIRFM determines the three-dimensional angular orientation and the
      extent of wobble of a fluorescent probe bound to the macromolecule of interest.
      This protocol describes the processive motility assay for investigating the
      motility of myosin V in vitro. Biotin-Alexa actin filaments are fixed to a slide
      by biotin/streptavidin linkages and aligned with the microscope x-axis by fluid
      flow. The orientation of a rhodamine-calmodulin (CaM) probe bound to a single
      myosin V molecule is determined as it moves along an actin filament. Excess wild
      type calmodulin (WT-CaM) is present in the buffer solution to replenish lost CaM
      from the myosin lever arm. The techniques for myosin V should be generally
      applicable to other single-molecule experiments where angular changes have an
      important mechanistic role in their biological function.

PMID- 22661445
TI  - Construction of flow chambers for polarized total internal reflection
      fluorescence microscopy (polTIRFM) motility assays.
AB  - Polarized total internal reflection fluorescence microscopy (polTIRFM) can be
      used to detect the spatial orientation and rotational dynamics of single
      molecules. polTIRFM determines the three-dimensional angular orientation and the
      extent of wobble of a fluorescent probe bound to the macromolecule of interest.
      This protocol describes how to construct sample chambers (flow chambers) for
      polTIRFM motility assays. Each chamber can hold ~20 uL of solution. To flow a
      solution through the chamber, the solution is added to the chamber with a pipette
      while wicking out the previous contents with filter paper. Each end of the
      coverslip should extend beyond the edge of the slide to support the pipette tip
      and filter paper. The flow rate can be roughly controlled by adjusting the
      contact area between the filter paper and the solution. The chambers can be used
      for investigating the motility of myosin V in vitro with the processive motility
      assay, as well as for assessing the motility of actin using the twirling assay.

PMID- 22661447
TI  - Genetic analysis of the O-antigen of Providencia alcalifaciens O30 and
      biochemical characterization of a formyltransferase involved in the synthesis of
      a Qui4N derivative.
AB  - O-Antigen is a component of the outer membrane of Gram-negative bacteria and one
      of the most variable cell surface constituents, giving rise to major antigenic
      variability. The diversity of O-antigen is almost entirely attributed to genetic
      variations in O-antigen gene clusters. Bacteria of the genus Providencia are
      facultative pathogens, which can cause urinary tract infections, wound infections
      and enteric diseases. Recently, the O-antigen gene cluster of Providencia was
      localized between the cpxA and yibK genes in the genome. However, few genes
      involved in the synthesis of Providencia O-antigens have been functionally
      identified. In this study, the putative O-antigen gene cluster of Providencia
      alcalifaciens O30 was sequenced and analyzed. Almost all putative genes for the O
      antigen synthesis were found, including a novel formyltransferase gene vioF that
      was proposed to be responsible for the conversion of dTDP-4-amino-4,6- dideoxy-D
      glucose (dTDP-D-Qui4N) to dTDP-4,6-dideoxy-4-formamido-D-glucose (dTDP-D
      Qui4NFo). vioF was cloned, and the enzyme product was expressed as a His-tagged
      fusion protein, purified and assayed for its activity. High-performance liquid
      chromatography was used to monitor the enzyme-substrate reaction, and the
      structure of the product dTDP-D-Qui4NFo was established by electrospray
      ionization tandem mass spectrometry and nuclear magnetic resonance spectroscopy.
      Kinetic parameters of VioF were determined, and effects of temperature and
      cations on its activity were also examined. Together, the functional analyses
      support the identification of the O-antigen gene cluster of P. alcalifaciens O30.

PMID- 22661448
TI  - Neurally adjusted ventilatory assist vs pressure support ventilation for
      noninvasive ventilation during acute respiratory failure: a crossover physiologic
      study.
AB  - BACKGROUND: Patient-ventilator asynchrony is common during noninvasive
      ventilation (NIV) with pressure support ventilation (PSV). We examined the effect
      of neurally adjusted ventilatory assist (NAVA) delivered through a facemask on
      synchronization in patients with acute respiratory failure (ARF). METHODS: This
      was a prospective, physiologic, crossover study of 13 patients with ARF (median
      Pa(O(2))/F(IO(2)), 196 [interquartile range (IQR), 142-225]) given two 30-min
      trials of NIV with PSV and NAVA in random order. Diaphragm electrical activity
      (EAdi), neural inspiratory time (T(In)), trigger delay (Td), asynchrony index
      (AI), arterial blood gas levels, and patient discomfort were recorded. RESULTS:
      There were significantly fewer asynchrony events during NAVA than during PSV (10
      [IQR, 5-14] events vs 17 [IQR, 8-24] events, P = .017), and the occurrence of
      severe asynchrony (AI > 10%) was also less under NAVA (P = .027). Ineffective
      efforts and delayed cycling were significantly less with NAVA (P < .05 for both).
      NAVA was also associated with reduced Td (0 [IQR, 0-30] milliseconds vs 90 [IQR,
      30-130] milliseconds, P < .001) and inspiratory time in excess (10 [IQR, 0-28]
      milliseconds vs 125 [IQR, 20-312] milliseconds, P < .001), but T(In) was similar
      under PSV and NAVA. The EAdi signal to its maximal value was higher during NAVA
      than during PSV ( P = .017). There were no significant differences in arterial
      blood gases or patient discomfort under PSV and NAVA. CONCLUSION: In view of
      specific experimental conditions, our comparison of PSV and NAVA indicated that
      NAVA significantly reduced severe patient-ventilator asynchrony and resulted in
      similar improvements in gas exchange during NIV for ARF. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT01426178; URL: www.clinicaltrials.gov.

PMID- 22661450
TI  - Proadrenomedullin improves Risk of Early Admission to ICU score for predicting
      early severe community-acquired pneumonia.
AB  - BACKGROUND: Whether proadrenomedullin (ProADM) improves the performance of the
      Risk of Early Admission to ICU (REA-ICU) score in predicting early, severe
      community-acquired pneumonia (ESCAP) has not been demonstrated. METHODS:
      Secondary analysis was completed of the original data from 877 consecutive
      patients with community-acquired pneumonia (CAP) enrolled in the Procalcitonin
      Guided Antibiotic Therapy and Hospitalization in Patients With Lower Respiratory
      Tract Infections (ProHOSP) study, a multicenter trial in EDs of six tertiary-care
      hospitals in Switzerland. ESCAP was defined by either the requirement for
      mechanical ventilation or vasopressive drugs or occurrence of death within 3 days
      of ED presentation. RESULTS: Eighty patients (9.1%) developed ESCAP (47 required
      mechanical ventilation, 19 vasopressive drugs, and 16 died) within 3 days of ED
      presentation. They had a higher median ProADM value (2.18 nmol/L vs 1.15 nmol/L,
      P < .001). Combining ProADM testing with the REA-ICU score improved the area
      under the curve (0.81) compared with either parameter (ProADM [0.73] or REA-ICU
      score [0.76], P < .001) and resulted in a net reclassification improvement of
      0.20 (P < .001). A ProADM value >= 1.8 nmol/L or assignment to REA-ICU risk
      classes III-IV predicted ESCAP with a sensitivity of 76.3% and a negative
      predictive value of 96.7%. Excluding 21 patients with major criteria of severe
      CAP on presentation showed similar results. CONCLUSION: These study findings
      demonstrate that the addition of ProADM to the REA-ICU score improves the
      classification of a substantial proportion of patients in the ED at intermediate
      or high risk for ESCAP, which may translate into better triage decisions.

PMID- 22661451
TI  - Demographics and outcomes of patients diagnosed with pulmonary hypertension with
      pulmonary capillary wedge pressures 16 to 18 mm Hg: insights from the REVEAL
      Registry.
AB  - BACKGROUND: The Registry to Evaluate Early and Long-term Pulmonary Arterial
      Hypertension Disease Management (REVEAL Registry) is a multicenter, US-based,
      observational study of patients diagnosed with group 1 pulmonary hypertension
      enrolled consecutively from March 2006 to December 2009. Of 3,128 patients in
      this analysis, inclusion criteria permitted enrollment of 268 patients with mean
      pulmonary capillary wedge pressure (PCWP) 16 to 18 mm Hg at diagnostic right
      sided heart catheterization (RHC) (above currently accepted pulmonary arterial
      hypertension [PAH] diagnostic criteria). This study compared the demographics and
      outcomes of those 268 patients with an elevated mean PCWP to patients with a mean
      PCWP <= 15 mm Hg. METHODS: Demographic characteristics and outcomes were compared
      for patients with mean PCWP <= 12, 13 to 15, and 16 to 18 mm Hg at diagnostic and
      follow-up RHC. RESULTS: At diagnostic RHC, patients with PCWP 16 to 18 mm Hg were
      older, had more severe hemodynamic impairments, and were more likely to be obese
      and have other comorbidities than patients with PCWP <= 15 mm Hg. There were no
      clinically relevant differences in 5-year survival rates from diagnostic RHC
      regardless of PCWP at diagnosis (<= 15 mm Hg vs 16-18 mm Hg, P = .07). Two-year
      survival rates of 108 patients with PAH whose PCWP increased to 19 mm Hg
      (regardless of PCWP at diagnosis) were significantly lower than that of patients
      with PAH with PCWP <= 18 mm Hg at subsequent RHC. CONCLUSION: Patients with PCWP
      16 to 18 mm Hg who were diagnosed and treated for PAH were older, heavier, and
      more likely to have comorbidities associated with left ventricular diastolic
      dysfunction at diagnosis than those with PCWP <= 15 mm Hg. Five-year survival
      rates were similarly low for all PCWP subgroups. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov

PMID- 22661453
TI  - The effect of placebo conditioning on capsaicin-evoked urge to cough.
AB  - BACKGROUND: The urge to cough is a clinical symptom of respiratory disease that
      precedes the motor act of coughing. Although previous studies have shown that
      cough is particularly susceptible to placebo suppression, it is unclear whether
      the perception of an urge to cough is also modifiable by placebo. Therefore, we
      tested the hypothesis that capsaicin-evoked urge to cough could be suppressed by
      placebo conditioning. METHODS: Eleven healthy participants were unknowingly
      conditioned to believe that an inert inhaler temporarily suppressed capsaicin
      induced urge to cough by deceptively modifying the challenge concentration of
      capsaicin. In subsequent testing, capsaicin-evoked urge-to-cough subjective
      ratings were assessed in four challenges with a single dose of inhaled capsaicin
      following no treatment or the placebo metered-dose inhaler. An additional 10
      participants were informed that the inhaler therapy was inert prior to receiving
      capsaicin challenges with and without inhaler treatment. RESULTS: There was a
      significant decrease in mean urge-to-cough ratings to capsaicin challenge
      following placebo compared with no treatment followed by capsaicin challenge (P <
      .001), with a peak decrease of 45%. The placebo inhaler alone had no effect on
      urge-to-cough subjective ratings when participants were aware that it contained
      no active medication. CONCLUSIONS: These data confirm that the urge to cough is
      susceptible to placebo inhibition. This provides further evidence that higher
      brain networks are involved in the processing of respiratory sensations related
      to airway irritation.

PMID- 22661452
TI  - Brachial artery diameter and the right ventricle: the Multi-Ethnic Study of
      Atherosclerosis-right ventricle study.
AB  - BACKGROUND: Endothelial dysfunction is associated with left ventricular
      morphology and long-term cardiovascular outcomes. The purpose of this study was
      to assess the relationship between both baseline brachial artery diameter and
      peripheral endothelial function (assessed by brachial artery ultrasonography) and
      right ventricular (RV) mass, RV end-diastolic volume (RVEDV), and RV ejection
      fraction (RVEF). METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA)
      performed cardiac MRI and brachial artery ultrasonography on participants without
      clinical cardiovascular disease. Baseline brachial artery diameter and flow
      mediated dilation were assessed. RESULTS: The mean age was 60.9 years, and 49.4%
      of subjects were men (n = 2,425). In adjusted models, larger brachial artery
      diameter was strongly associated with greater RV mass (beta = 0.55 g, P < .001),
      larger RVEDV (beta = 3.99 mL, P < .001), and decreased RVEF (beta = -0.46%, P =
      .03). These relationships persisted after further adjustment for the respective
      left ventricular parameters. Flow-mediated dilation was not associated with RV
      mass or RVEF and was only weakly associated with RVEDV. CONCLUSIONS: Brachial
      artery diameter is associated with greater RV mass and RVEDV, as well as lower
      RVEF. Changes in the systemic arterial circulation may have pathophysiologic
      links to pulmonary vascular dysfunction or abnormalities in RV perfusion.

PMID- 22661454
TI  - Learned helplessness among families and surrogate decision-makers of patients
      admitted to medical, surgical, and trauma ICUs.
AB  - BACKGROUND: We sought to determine the prevalence of and clinical variables
      associated with learned helplessness, a psychologic state characterized by
      reduced motivation, difficulty in determining causality, and depression, in
      family members of patients admitted to ICUs. METHODS: We conducted an
      observational survey study of a prospectively defined cohort of family members,
      spouses, and partners of patients admitted to surgical, medical, and trauma ICUs
      at a large academic medical center. Two validated instruments, the Learned
      Helplessness Scale and the Perceived Stress Scale, were used, and self-report of
      patient clinical characteristics and subject demographics were collected.
      RESULTS: Four hundred ninety-nine family members were assessed. Of these, 238 of
      460 (51.7%) had responses consistent with a significant degree of learned
      helplessness. Among surrogate decision-makers, this proportion was 50% (92 of
      184). Characteristics associated with significant learned helplessness included
      grade or high school education (OR, 3.27; 95% CI, 1.29-8.27; P = .01) and
      Perceived Stress Scale score > 18 (OR, 4.15; 95% CI, 2.65-6.50; P < .001). The
      presence of a patient advance directive or do not resuscitate (DNR) order was
      associated with reduced odds of significant learned helplessness (OR, 0.56; 95%
      CI, 0.32-0.98; P = .05). CONCLUSIONS: The majority of family members of patients
      in the ICU experience significant learned helplessness. Risk factors for learned
      helplessness include lower educational levels, absence of an advance directive or
      DNR order, and higher stress levels among family members. Significant learned
      helplessness in family members may have negative implications in the
      collaborative decision-making process.

PMID- 22661455
TI  - Identifying elements of ICU care that families report as important but
      unsatisfactory: decision-making, control, and ICU atmosphere.
AB  - BACKGROUND: One in fi ve deaths in the United States occurs in the ICU, and many
      of these deaths are experienced as less than optimal by families of dying people.
      The current study investigated the relationship between family satisfaction with
      ICU care and overall ratings of the quality of dying as a means of identifying
      targets for improving end-of-life experiences for patients and families. METHODS:
      This multisite cross-sectional study surveyed families of patients who died in
      the ICU in one of 15 hospitals in western Washington State. Measures included the
      Family Satisfaction in the ICU (FS-ICU) and the Single-Item Quality of Dying (QOD
      1) questionnaires. Associations between FS-ICU items and the QOD-1 were examined
      using multivariate linear regression controlling for patient and family
      demographics and hospital site. RESULTS: Questionnaires were returned for 1,290
      of 2,850 decedents (45%). Higher QOD-1 scores were significantly associated (all
      P < .05) with (1) perceived nursing skill and competence (beta= 0.15), (2)
      support for family as decision-makers ( beta= 0.10), (3) family control over the
      patient's care( beta= 0.18), and (4) ICU atmosphere (beta= 0.12). FS-ICU items
      that received low ratings and correlated with higher QOD-1 scores (ie, important
      items with room for improvement) were (1) support of family as decision-maker,
      (2) family control over patient's care, and (3) ICU atmosphere. CONCLUSIONS:
      Increased support for families as decision-makers and for their desired level of
      control over patient care along with improvements in the ICU atmosphere were
      identified as aspects of the ICU experience that may be important targets for
      quality improvement. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00685893; URL:
      www.clinicaltrials.gov.

PMID- 22661457
TI  - Ethics, organ donation and tax: a reply to Quigley and Taylor.
AB  - A national opt-out system of post-mortem donation of scarce organs is preferable
      to an opt-in system. Unfortunately, the former system is not always feasible, and
      so in a recent JME article we canvassed the possibility of offering people a tax
      break for opting-in as a way of increasing the number of organs available for
      donation under an opt-in regime. Muireann Quigley and James Stacey Taylor
      criticize our proposal. Roughly, Quigley argues that our proposal is costly and,
      hence, is unlikely to be implemented, while Taylor contests our response to a
      Titmuss-style objection to our scheme. In response to Quigley, we note that our
      proposal's main attraction lies in gains not reflected in the figures presented
      by Quigley and that the mere fact that it is costly does not imply that it is
      unfeasible. In response to Taylor, we offer some textual evidence in support of
      our interpretation of Taylor and responds to his favoured interpretation of the
      Titmuss-style objection that many people seem to want to donate to charities even
      if they can deduct their donations from their income tax. Finally, we show why
      our views do not commit us to endorsing a free organ-market.

PMID- 22661456
TI  - Quantitative proteomic analysis of type III secretome of enteropathogenic
      Escherichia coli reveals an expanded effector repertoire for attaching/effacing
      bacterial pathogens.
AB  - Type III secretion systems are central to the pathogenesis and virulence of many
      important Gram-negative bacterial pathogens, and elucidation of the secretion
      mechanism and identification of the secreted substrates are critical to our
      understanding of their pathogenic mechanisms and developing potential
      therapeutics. Stable isotope labeling with amino acids in cell culture-based mass
      spectrometry is a quantitative and highly sensitive proteomics tool that we have
      previously used to successfully analyze the type III secretomes of Citrobacter
      rodentium and Salmonella enterica serovar Typhimurium. In this report, stable
      isotope labeling with amino acids in cell culture was used to analyze the type
      III secretome of enteropathogenic Escherichia coli (EPEC), an important human
      pathogen, which, together with enterohemorrhagic E. coli and C. rodentium,
      represents the family of attaching and effacing bacterial pathogens. We not only
      confirmed all 25 known EPEC type III-secreted proteins and effectors previously
      identified by conventional molecular and bioinformatical techniques but also
      identified several new type III-secreted proteins, including two novel effectors,
      C_0814/NleJ and LifA, that were shown to be translocated into host cells. LifA is
      a known virulence factor believed to act as a toxin as well as an adhesin, but
      its mechanism of secretion and function is not understood. With a predicted
      molecular mass of 366 kDa, LifA is the largest type III effector identified thus
      far in any pathogen. We further demonstrated that Efa1, ToxB, and Z4332 (homologs
      of LifA in enterohemorrhagic E. coli) are also type III effectors. This study has
      comprehensively characterized the type III secretome of EPEC, expanded the
      repertoire of type III-secreted effectors for the attaching and effacing
      pathogens, and provided new insights into the mode of function for
      LifA/Efa1/ToxB/Z4332, an important family of virulence factors.

PMID- 22661458
TI  - The national colonoscopy audit: a nationwide assessment of the quality and safety
      of colonoscopy in the UK.
AB  - OBJECTIVE: To perform a comprehensive audit of all colonoscopy undertaken in the
      UK over a 2-week period. DESIGN: Multi-centre survey. All adult (>=16 years of
      age) colonoscopies that took place in participating National Health Service
      hospitals between 28 February 2011 and 11 March 2011 were included. RESULTS: Data
      on 20,085 colonoscopies and 2681 colonoscopists were collected from 302 units. A
      validation exercise indicated that data were collected on over 94% of all
      procedures performed nationally. The unadjusted caecal intubation rate (CIR) was
      92.3%. When adjusted for impassable strictures and poor bowel preparation the CIR
      was 95.8%. The polyp detection rate was 32.1%. The polyp detection rate for
      larger polyps (>=10 mm diameter) was 11.7%. 92.3% of resected polyps were
      retrieved. 90.2% of procedures achieved acceptable levels of patient comfort. A
      total of eight perforations and 52 significant haemorrhages were reported. Eight
      patients underwent surgery as a consequence of a complication. CONCLUSIONS: This
      is the first national audit of colonoscopy that has successfully captured the
      majority of adult colonoscopies performed across an entire nation during a
      defined time period. The data confirm that there has been a significant
      improvement in the performance of colonoscopy in the UK since the last study
      reported seven years ago (CIR 76.9%) and that performance is above the required
      national standards.

PMID- 22661459
TI  - Study design biases in pancreatic inflammatory diseases.

PMID- 22661460
TI  - Rapid RP-HPLC method for the quantification of glabridin in crude drug and in
      polyherbal formulation.
AB  - A simple, economic, selective, precise and robust method has been developed and
      validated for the analysis of glabridin in crude drugs and polyherbal
      formulations. Reversed-phase chromatography is performed on a C18 column with
      water and acetonitrile as mobile phase in gradient elution method at a flow rate
      of 1 mL/min. Detection is performed at 230 nm and a sharp peak is obtained for
      glabridin at a retention time of 14.9 +/- 0.02 min. Linear regression analysis
      data for the calibration plot showed a good linear relationship between response
      and concentration in the range of 1-500 ug/mL; the regression coefficient is
      0.9992 and the linear regression equation is y = 26.683x - 142.17. The method is
      validated for accuracy, precision, reproducibility, robustness and detection and
      quantification limits, in accordance with International Conference on
      Harmonization guidelines. Statistical analysis proved that the method is precise,
      reproducible, selective and accurate for the analysis of glabridin. The proposed,
      developed and validated high-performance liquid chromatography method for the
      quantification of glabridin can be used for the quality control and
      standardization of licorice (Glycyrrhiza glabra Linn.) and different herbal
      formulations in which licorice is present as a constituent.

PMID- 22661461
TI  - UPLC and LC-MS studies on degradation behavior of irinotecan hydrochloride and
      development of a validated stability-indicating ultra-performance liquid
      chromatographic method for determination of irinotecan hydrochloride and its
      impurities in pharmaceutical dosage forms.
AB  - The objective of the current investigation was to study the degradation behavior
      of irinotecan hydrochloride under different International Conference on
      Harmonization (ICH) recommended stress conditions using ultra-performance liquid
      chromatography and liquid chromatography-mass spectrometry and to establish a
      validated stability-indicating reverse-phase ultra-performance liquid
      chromatographic method for the quantitative determination of irinotecan
      hydrochloride and its seven impurities and degradation products in pharmaceutical
      dosage forms. Irinotecan hydrochloride was subjected to the stress conditions of
      oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Irinotecan
      hydrochloride was found to degrade significantly in oxidative and base hydrolysis
      and photolytic degradation conditions. The degradation products were well
      resolved from the main peak and its impurities, thus proving the stability
      indicating power of the method. Chromatographic separation was achieved on a
      Waters Acquity BEH C8 (100 * 2.1 mm) 1.7-um column with a mobile phase containing
      a gradient mixture of solvent A (0.02M KH(2)PO(4) buffer, pH 3.4) and solvent B
      (a mixture of acetonitrile and methanol in the ratio of 62:38 v/v). The mobile
      phase was delivered at a flow rate of 0.3 mL/min with ultraviolet detection at
      220 nm. The run time was 8 min, within which irinotecan and its seven impurities
      and degradation products were satisfactorily separated. The developed method was
      validated as per ICH guidelines with respect to specificity, linearity, limit of
      detection, limit of quantification, accuracy, precision and robustness. This
      method was also suitable for the assay determination of irinotecan hydrochloride
      in pharmaceutical dosage forms.

PMID- 22661462
TI  - Thermal load from a CO2 laser radiant energy source induces changes in corneal
      surface asphericity, roughness, and transverse contraction.
AB  - PURPOSE: We examined corneal surface response to an isolated thermal load.
      METHODS: Cadaveric porcine eyes were pressurized and stabilized for processing
      and imaging. A carbon dioxide (CO2) laser (1.75 W) delivered a uniform disk of
      continuous wave thermal radiant energy to the exposed corneal stromal surface
      without ablation. Thermal load was determined by measuring corneal surface
      temperature during CO2 laser irradiation. Corneal profilometry was measured with
      broad-band optical interferometry before and after CO2 laser irradiation.
      Photomicrographs of the stromal surface were taken before and after irradiation,
      and the images were superimposed to examine changes in positional marks,
      examining mechanical alterations in the stromal surface. RESULTS: Thermal load
      from uniform laser irradiation without ablation produces central corneal
      steepening and paracentral flattening in the central 3-mm diameter. Q values,
      measuring asphericity in the central 2 mm of the cornea increased significantly
      and it was correlated with the temperature rise (R2=0.767). Surface roughness
      increased significantly and also was correlated with temperature rise (R2=0.851).
      The central stromal surface contracted and underwent characteristic morphologic
      changes with the applied thermal load, which correlated well with the temperature
      rise (R2=0.818). CONCLUSIONS: The thermal load created by CO2 laser irradiation
      creates a characteristic spectrum of morphologic changes on the porcine corneal
      stromal surface that correlates to the temperature rise and is not seen with
      inorganic, isotropic material. The surface changes demonstrated with the CO2
      laser likely are indicative of temperature-induced transverse collagen fibril
      contraction and stress redistribution. Refractive procedures that produce
      significant thermal load should be cognizant of these morphologic changes.

PMID- 22661463
TI  - Gene repair of an Usher syndrome causing mutation by zinc-finger nuclease
      mediated homologous recombination.
AB  - PURPOSE: Human Usher syndrome (USH) is the most frequent cause of inherited deaf
      blindness. It is clinically and genetically heterogeneous, assigned to three
      clinical types of which the most severe type is USH1. No effective treatment for
      the ophthalmic component of USH exists. Gene augmentation is an attractive
      strategy for hereditary retinal diseases. However, several USH genes, like USH1C,
      are expressed in various isoforms, hampering gene augmentation. As an alternative
      treatment strategy, we applied the zinc-finger nuclease (ZFN) technology for
      targeted gene repair of an USH1C, causing mutation by homologous recombination.
      METHODS: We designed ZFNs customized for the p.R31X nonsense mutation in Ush1c.
      We evaluated ZFNs for DNA cleavage capability and analyzed ZFNs
      biocompatibilities by XTT assays. We demonstrated ZFNs mediated gene repair on
      genomic level by digestion assays and DNA sequencing, and on protein level by
      indirect immunofluorescence and Western blot analyses. RESULTS: The specifically
      designed ZFNs did not show cytotoxic effects in a p.R31X cell line. We
      demonstrated that ZFN induced cleavage of their target sequence. We showed that
      simultaneous application of ZFN and rescue DNA induced gene repair of the disease
      causing mutation on the genomic level, resulting in recovery of protein
      expression. CONCLUSIONS: In our present study, we analyzed for the first time ZFN
      activated gene repair of an USH gene. The data highlight the ability of ZFNs to
      induce targeted homologous recombination and mediate gene repair in USH. We
      provide further evidence that the ZFN technology holds great potential to recover
      disease-causing mutations in inherited retinal disorders.

PMID- 22661465
TI  - En face enhanced depth imaging optical coherence tomography of fibrovascular
      pigment epithelium detachment.
AB  - PURPOSE: To analyze the internal structure of fibrovascular pigment epithelial
      detachment (FV-PED) due to AMD using en face enhanced depth imaging (EDI)
      spectral-domain optical coherence tomography (SD-OCT). METHODS: Thirty-eight
      consecutive patients presenting with FV-PED due to AMD were enrolled in this
      study. Retinal images were automatically obtained with a spectral domain (SD) OCT
      instrument; the typical inverted 97 sections at 30-MUm intervals, each comprised
      of nine averaged B-scans, were acquired in less than 60 seconds. The resultant
      images of en face cross-sections of the choroid (C-scans) were compared with
      indocyanine green angiography (ICGA) images, currently the only technique
      available for directly viewing occult choroidal neovascularization (CNV).
      RESULTS: Thirty-eight eyes of 38 consecutive patients (27 females and 11 males,
      mean age 76.7+/-3 years) were studied. In all 38 eyes, ICGA allowed visualization
      of the CNV within the FV-PED. In 30 eyes, en face EDI-OCT revealed what appeared
      to be the hyperreflective course of presumed CNV, which was located just beneath
      the detached retinal pigment epithelium; this was confirmed by comparative
      analysis of the extent of hyperreflective lesions on en face EDI-OCT images and
      that of the neovascular network on ICGA. An area of homogeneous hyporeflectivity,
      consistent with serous exudation, separated the CNV from the Bruch's membrane and
      the choroid. In the remaining eight eyes, en face EDI-OCT revealed homogenous
      hyperreflectivity, consistent with fibrous tissue that partially hid the
      neovascular network. CONCLUSIONS: Noninvasive en face EDI-OCT technique enables
      visualization and localization of the entire branching neovascular network of CNV
      within FV-PED without dye injection.

PMID- 22661464
TI  - Use of the Argus II retinal prosthesis to improve visual guidance of fine hand
      movements.
AB  - PURPOSE: We studied the capabilities of the Argus II retinal prosthesis for
      guiding fine hand movement, and demonstrated and quantified guidance improvement
      when using the device over when not using the device for progressively less
      predictable trajectories. METHODS: A total of 21 patients with retinitis
      pigmentosa (RP), remaining vision no more than bare light perception, and an
      implanted Argus II epiretinal prostheses used a touchscreen to trace white paths
      on black backgrounds. Sets of paths were divided into three categories: right
      angle/single-turn, mixed-angle/single-turn, and mixed-angle/two-turn. Subjects
      trained on paths by using prosthetic vision and auditory feedback, and then were
      tested without auditory feedback, with and without prosthetic vision. Custom
      software recorded position and timing information for any contact that subjects
      made with the screen. The area between the correct path and the trace, and the
      elapsed time to trace a path were used to evaluate subject performance. RESULTS:
      For right-angle/single-turn sets, average tracing error was reduced by 63% and
      tracing time increased by 156% when using the prosthesis, relative to residual
      vision. With mixed-angle/single-turn sets, error was reduced by 53% and time to
      complete tracing increased by 184%. Prosthesis use decreased error by 38% and
      increased tracing time by 252% for paths that incorporated two turns.
      CONCLUSIONS: Use of an epiretinal visual prosthesis can allow RP patients with no
      more than bare light perception to guide fine hand movement visually. Further,
      prosthetic input tends to make subjects slower when performing tracing tasks,
      presumably reflecting greater effort. (ClinicalTrials.gov number, NCT01123928.)

PMID- 22661467
TI  - Double concentric autofluorescence ring in NR2E3-p.G56R-linked autosomal dominant
      retinitis pigmentosa.
AB  - PURPOSE: We reported an unusual appearance of fundus autofluorescence (FAF)
      associated with NR2E3-p.G56R-linked autosomal dominant retinitis pigmentosa
      (ADRP). METHODS: Patients were enrolled among three generations in a Swiss
      family. Molecular diagnosis identified a c.166G > A (p.G56R) mutation. Ophthalmic
      examination included fundus photography, FAF near-infrared autofluorescence
      (NIA), optical coherence tomography (OCT), and visual fields (VF). RESULTS:
      Fundus examination revealed a wide range of features from unremarkable to
      attenuated arterial caliber, clumped and spicular pigment deposits in the mid
      periphery and optic nerve pallor. FAF showed a double concentric
      hyperautofluorescent ring: an inner perimacular ring that tended to be smaller in
      older patients, and an outer ring located along the vascular arcades, which
      appeared to extend over time toward the periphery and eventually became
      hypoautofluorescent. The inner and outer hyperautofluorescent rings were seen
      both on NIA and FAF at a similar localization. There was also a spatial
      correspondence between the loss of photoreceptor inner segment and outer segment
      junction on OCT and the area delimited by both double FAF and NIA rings. VF
      showed either mid-peripheral annular scotoma or constricted visual field loss in
      advanced cases, correlating with dystrophic nonfunctional retinal regions
      demarcated by the hyperautofluorescent annuli. A double ring of
      hyperautofluorescence was observed in all but one patient of two additional
      families, but not in patients harboring mutations in other ADRP genes, including
      PRPF3, RHO, RP1, PRPH2, PROM1, and CTRP5. CONCLUSIONS: The presence of a double
      concentric hyperautofluorescent ring of FAF may represent a highly penetrant
      early phenotypic marker of NR2E3-p.G56R-linked ADRP.

PMID- 22661466
TI  - Blood flow MRI of the human retina/choroid during rest and isometric exercise.
AB  - PURPOSE: To investigate blood flow (BF) in the human retina/choroid during rest
      and handgrip isometric exercise using magnetic resonance imaging (MRI). METHODS:
      Four healthy volunteers (25-36 years old) in multiple sessions (1-3) on different
      days. MRI studies were performed on a 3-Tesla scanner using a custom-made surface
      coil (7*5cm in diameter) at the spatial resolution of 0.5*0.8*6.0 mm. BF was
      measured using the pseudo-continuous arterial-spin-labeling technique with
      background suppression and turbo-spin-echo acquisition. During MRI, subjects
      rested for 1 minute followed by 1 minute of handgrip, repeating three times,
      while maintaining stable eye fixation on a target with cued eye blinks at the end
      of each data acquisition (every 4.6 seconds). RESULTS: Robust BF of the
      unanesthetized human retina/choroid was detected. Basal BF in the posterior
      retina/choroid was 149+/-48 mL/100 mL/min with a mean heart rate of 60+/-5 beats
      per minute, mean arterial pressure of 78+/-5 mm Hg, ocular perfusion pressure of
      67+/-4 mm Hg at rest (mean+/-SD, n=4 subjects). Handgrip significantly increased
      retina/choroid BF by 25%+/-7%, heart rate by 19%+/-8%, mean arterial pressure by
      22%+/-5% (measured at the middle of the handgrip task), and ocular perfusion
      pressure by 25%+/-6% (averaged across the entire handgrip task) (P<0.01), but did
      not change intraocular pressure, arterial oxygen saturation, end-tidal CO2, and
      respiration rate (P>0.05). CONCLUSIONS: This study demonstrates a novel MRI
      application to image quantitative BF of the human retina/choroid during rest and
      isometric exercise. Retina/choroid BF increases during brief handgrip exercise,
      paralleling increases in mean arterial pressure. Handgrip exercise changes ocular
      perfusion pressure free of potential drug side effect and can be done in the MRI
      scanner. MRI offers quantitative BF with large field of view without depth
      limitation, potentially providing insights into retinal pathophysiology.

PMID- 22661468
TI  - Quantitative evaluation of papilledema from stereoscopic color fundus
      photographs.
AB  - PURPOSE: To derive a computerized measurement of optic disc volume from digital
      stereoscopic fundus photographs for the purpose of diagnosing and managing
      papilledema. METHODS: Twenty-nine pairs of stereoscopic fundus photographs and
      optic nerve head (ONH) centered spectral domain optical coherence tomography (SD
      OCT) scans were obtained at the same visit in 15 patients with papilledema. Some
      patients were imaged at multiple visits in order to assess their changes. Three
      dimensional shape of the ONH was estimated from stereo fundus photographs using
      an automated multi-scale stereo correspondence algorithm. We assessed the
      correlation of the stereo volume measurements with the SD-OCT volume measurements
      quantitatively, in terms of volume of retinal surface elevation above a reference
      plane and also to expert grading of papilledema from digital fundus photographs
      using the Frisen grading scale. RESULTS: The volumetric measurements of retinal
      surface elevation estimated from stereo fundus photographs and OCT scans were
      positively correlated (correlation coefficient r(2) = 0.60; P < 0.001) and were
      positively correlated with Frisen grade (Spearman correlation coefficient r =
      0.59; P < 0.001). CONCLUSIONS: Retinal surface elevation among papilledema
      patients obtained from stereo fundus photographs compares favorably with that
      from OCT scans and with expert grading of papilledema severity. Stereoscopic
      color imaging of the ONH combined with a method of automated shape reconstruction
      is a low-cost alternative to SD-OCT scans that has potential for a more cost
      effective diagnosis and management of papilledema in a telemedical setting. An
      automated three-dimensional image analysis method was validated that quantifies
      the retinal surface topography with an imaging modality that has lacked prior
      objective assessment.

PMID- 22661469
TI  - Preservation of retina ganglion cell function by morphine in a chronic ocular
      hypertensive rat model.
AB  - PURPOSE: The current study examined if opioid-receptor-activation by morphine can
      improve retinal function and retinal ganglion cell (RGC) integrity in a chronic
      glaucoma rat model. METHODS: IOP was raised in Brown Norway rats by injecting
      hypertonic saline into the limbal venous system. Rats were treated daily with 1
      mg/kg morphine for 28 days at 24-hour intervals; animals were examined for
      changes in IOP by a TonoLab tonometer. Pattern-ERG (PERG) was obtained in
      response to contrast-reversal of patterned visual stimuli. RGCs were visualized
      by fluorogold retrograde-labeling. Changes in the expression pattern of TNF-alpha
      and caspases were measured by Western blotting. RESULTS: A significant IOP
      elevation was seen as early as 7 days, and maintained for up to 8 weeks, after
      surgery. PERG amplitudes were significantly reduced in ocular-hypertensive eyes
      (15.84+/-0.74 MUvolts) when compared with normal eyes (19+/-0.86 MUvolts). PERG
      deficits in hypertensive eyes were reversed by morphine treatment (18.23+/-0.78
      MUvolts; P<0.05). In untreated rats, a 24% reduction in labeled RGCs was measured
      in the hypertensive eye compared with the normal eye. This reduction in RGC
      labeling was significantly ameliorated in the presence of morphine. In retinal
      samples, TNF-alpha, caspase-8, and caspase-3 expressions were significantly
      upregulated in ocular hypertensive eyes, but completely inhibited in the morphine
      treated animals. CONCLUSIONS: These data provide evidence that activation of
      opioid receptors can provide significant improvement in PERG and RGC integrity
      against glaucomatous injury. Mechanistic data provide clues that activation of
      one or more opioid receptors can reduce glaucomatous-injury via suppression of
      TNF-alpha and caspase activation.

PMID- 22661470
TI  - Neuroprotective effects of angiotensin II type 1 receptor (AT1-R) blocker via
      modulating AT1-R signaling and decreased extracellular glutamate levels.
AB  - PURPOSE: To investigate the mechanism of the neuroprotective effects of the
      angiotensin II type 1 receptor (AT1-R) blocker against retinal ischemia
      reperfusion injury in the rat. METHODS: Retinal ischemia was induced by
      increasing intraocular pressure. Glutamate release from the rat retina and
      intravitreal PO(2) (partial pressure of oxygen) profiles were monitored during
      and after ischemia using a microdialysis biosensor and oxygen-sensitive
      microelectrodes. ELISA was used to measure changes in the expression of AT1-R.
      Retinal mRNA expressions of p47phox and p67phox were measured by real-time
      polymerase chain reaction. Reactive oxygen species (ROS) were measured using
      dihydroethidium. RESULTS: Administration of candesartan, which is an AT1-R
      blocker (ARB), suppressed ischemia-induced increases in the extracellular
      glutamate. Candesartan also attenuated the increase in intravitreal PO(2) during
      reperfusion. AT1-R expression peaked at 12 hours after reperfusion. Although
      there was an increase in the retinal mRNA expression of p47phox and p64phox at 12
      hours after the reperfusion, administration of candesartan suppressed these
      expressions. The production of ROS that was detected at 12 hours after
      reperfusion was also suppressed by the administration of candesartan or apocynin.
      CONCLUSIONS: NADPH oxidase-mediated ROS production increased at 12 hours after
      reperfusion. Candesartan may protect neurons by decreasing extracellular
      glutamate immediately after reperfusion and by attenuating oxidative stress via a
      modulation of the AT1-R signaling that occurs during ischemic insult.

PMID- 22661471
TI  - Methylene blue protects primary rat retinal ganglion cells from cellular
      senescence.
AB  - PURPOSE: Glaucoma is a progressive optic neuropathy characterized by loss of
      retinal ganglion cells (RGCs) and optic nerve degradation. Existing treatments
      focus on lowering IOP; however, vision loss may still progress. Neuroprotective
      drugs may be useful as an adjunct approach to prevent further loss of RGCs,
      although efficacious drugs are lacking. One agent, methylene blue, protects
      neurons during several neurodegenerative models. Methylene blue potentiates the
      electron transport chain by shuttling elections from NADH and FADH2 to coenzyme Q
      (CoQ) and cytochrome c. The purpose of this study was to determine if methylene
      blue could protect RGCs from noxious stimuli. METHODS: Primary rat RGCs were
      isolated and cultured following a sequential immunopanning technique using P3-P7
      Sprague-Dawley rats. Approximately 25,000 RGCs were seeded per coverslip and
      cultured for 3 days before testing. The RGCs were treated for 24 hours with
      rotenone or staurosporine or for 72 hours of hypoxia. Methylene blue was then
      assessed for protection of RGCs during each of these insults. Cell viability was
      measured using calcein Am and ethidium homodimer-1. Cytochrome c oxidase activity
      was measured using a cytochrome c oxidase assay kit to monitor the health of
      mitochondria. RESULTS: Methylene blue (1 MUM and 10 MUM) significantly protected
      RGCs against 24 hours of 1 MUM rotenone. Methylene blue (1 MUM and 10 MUM)
      significantly protected RGCs against 24 hours of treatment with 1 MUM
      staurosporine and protected RGCs against 72 hours of hypoxia. Methylene blue
      increased cytochrome c oxidase activity in the presence of hydrogen peroxide.
      CONCLUSIONS: Methylene blue is a neuroprotective compound that can protect RGCs
      from toxic insults. Methylene blue's ability to increase cytochrome c oxidase and
      protect RGCs against these noxious stimuli supports its suggested mechanism of
      action, which is to preserve the electron transport chain. Further testing is
      needed to determine if methylene blue would be an efficacious treatment for the
      protection of neurodegeneration that occurs during optic neuropathy.

PMID- 22661472
TI  - Correlation between photoreceptor layer integrity and visual function in patients
      with Stargardt disease: implications for gene therapy.
AB  - PURPOSE: To perform a clinical characterization of Stargardt patients with ABCA4
      gene mutation, and to investigate the correlation between the inner and outer
      segment (IS/OS) junction morphology and visual acuity, fundus lesions,
      electroretinogram abnormalities, and macular sensitivity. METHODS: Sixty-one
      patients with Stargardt disease (STGD) were given a comprehensive ophthalmic
      examination. Inner-outer photoreceptor junction morphology evaluated by spectral
      domain optical coherence tomography was correlated with visual acuity, fundus
      lesions, fundus autofluorescence, full-field and multifocal electroretinography
      responses, and microperimetric macular sensitivities. We classified STGD patients
      into three groups: (1) IS/OS junction disorganization in the fovea, (2) IS/OS
      junction loss in the fovea, and (3) extensive loss of IS/OS junction. Mutation
      analysis of the ABCA4 gene was carried out by sequencing the complete coding
      region. RESULTS: A significant difference in visual acuity was observed between
      IS/OS groups 1 and 2 and between IS/OS groups 2 and 3 (P < 0.0001). A significant
      difference in microperimetry sensitivity was observed between IS/OS groups 2 and
      3, and between IS/OS groups 1 and 3 (P < 0.0001). There was also a statistically
      significant correlation between IS/OS abnormalities and the extent of fundus
      lesions (Spearman P <= 0.01), as well as with the type of ERG and multifocal ERG
      results (Spearman P <= 0.01). Finally, the degree of IS/OS junction preservation
      showed a statistically significant correlation with the extension of foveal
      abnormalities assessed by fundus autofluorescence imaging (Spearman P <= 0.01).
      The G1961E mutation was more frequent in the patients without extensive loss of
      IS/OS junction (P = 0.01) confirming its association with a milder STGD
      phenotype. CONCLUSIONS: The results of this study suggest that a comprehensive
      approach in the examination of Stargardt patients has the potential to improve
      the understanding of vision loss and may provide a sensitive measure to evaluate
      the efficacy of future experimental therapies in patients with STGD.

PMID- 22661474
TI  - A new epidemiological aid in deciding whether to continue or stop a treatment.
AB  - PURPOSE: To present a new epidemiological method relying on randomized controlled
      clinical trial (RCT) data to assess whether a treatment was effective, aiding in
      the decision to continue or stop the treatment in clinical patients. METHODS: A
      cutoff point is calculated in the change of a continuous outcome for which a
      proportion of treated patients clearly achieved a change better than this cutoff
      point as a result of the treatment. This cutoff point can then be applied to
      individual patients during routine therapy. The method was applied to reports of
      the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the
      Treatment of Neovascular AMD (MARINA) trial, which included patients with AMD
      treated with monthly intravitreal injections of ranibizumab, and to reports of
      trials involving patients with high IOP, macular edema, and convergence
      insufficiency. RESULTS: The cutoff point in the change in visual acuity (number
      of letters), above which a proportion of patients clearly benefited due to
      ranibizumab treatment, was -5.0 at 24 months follow-up. The proportion of treated
      patients who ended above this cutoff point due to the treatment was 60%. The
      cutoff point varies with time of follow-up and by subgroup. CONCLUSIONS: Contrary
      to common interpretation, no change, or a limited decline, in the outcome (visual
      acuity) can still imply that the patients are better off with the treatment than
      with no treatment. Stopping the treatment above the cutoff point may not be
      appropriate since it was effective in at least a proportion of patients. This
      method applies to a broad range of scales and conditions. (ClinicalTrials.gov
      number, NCT00056836.).

PMID- 22661473
TI  - Retinal phenotypes in patients homozygous for the G1961E mutation in the ABCA4
      gene.
AB  - PURPOSE: We evaluated the pathogenicity of the G1961E mutation in the ABCA4 gene,
      and present the range of retinal phenotypes associated with this mutation in
      homozygosity in a patient cohort with ABCA4-associated phenotypes. METHODS:
      Patients were enrolled from the ABCA4 disease database at Columbia University or
      by inquiry from collaborating physicians. Only patients homozygous for the G1961E
      mutation were enrolled. The entire ABCA4 gene open reading frame, including all
      exons and flanking intronic sequences, was sequenced in all patients. Phenotype
      data were obtained from clinical history and examination, fundus photography,
      infrared imaging, fundus autofluorescence, fluorescein angiography, and spectral
      domain-optical coherence tomography. Additional functional data were obtained
      using the full-field electroretinogram, and static or kinetic perimetry. RESULTS:
      We evaluated 12 patients homozygous for the G1961E mutation. All patients had
      evidence of retinal pathology consistent with the range of phenotypes observed in
      ABCA4 disease. The latest age of onset was recorded at 64 years, in a patient
      diagnosed initially with age-related macular degeneration (AMD). Of 6 patients in
      whom severe structural (with/without functional) fundus changes were detected, 5
      had additional, heterozygous or homozygous, variants detected in the ABCA4 gene.
      CONCLUSIONS: Homozygous G1961E mutation in ABCA4 results in a range of retinal
      pathology. The phenotype usually is at the milder end of the disease spectrum,
      with severe phenotypes linked to the presence of additional ABCA4 variants. Our
      report also highlights that milder, late-onset Stargardt disease may be confused
      with AMD.

PMID- 22661476
TI  - Induction and mechanism of apoptosis by hydroxycamptothecin in human Tenon's
      capsule fibroblasts.
AB  - PURPOSE: We investigated apoptosis induced by hydroxycamptothecin (HCPT) in human
      Tenon's capsule using fibroblasts cultured from human Tenon's capsule (HTFs), and
      the mechanism of induction. METHODS: HTFs were treated with 0-4 mg/L HCPT for 24
      hours. Cell proliferation was measured by 3-(4,5-dimethylthiazolyl-2)-2,5
      diphenyltetrazolium bromide (MTT) assay, and apoptotic cells were analyzed by
      Hoechst 33258 stain. The mRNA and protein levels of caspase-3, -8, and -9 were
      detected by RT-PCR and Western blotting. RESULTS: By MTT assay, HCPT induced
      apoptosis in HTFs in a concentration- and time-dependent manner. Hoechst 33258
      staining and transmission electron microscopy showed typical apoptotic
      morphology, such as condensed chromatin, irregular nuclei, and apoptotic body
      formation. The mRNA and protein levels of caspase-3 and caspase-9 were
      upregulated, while caspase-8 was unchanged. Z-VAD-FMK, a caspase inhibitor,
      inhibited the apoptosis of fibroblasts induced by HCPT. The expression levels of
      caspase-3 and caspase-9 were down-regulated after Z-VAD-FMK treatment.
      CONCLUSIONS: Caspase-3 and caspase-9 are important elements in regulating HCPT
      induced apoptosis in HTFs.

PMID- 22661475
TI  - Intravitreal anti-VEGF therapy blocks inflammatory cell infiltration and re-entry
      into the circulation in retinal angiogenesis.
AB  - PURPOSE: Anti-VEGF-A antibody (Ab) (e.g., bevacizumab, ranibizumab) is widely
      used as a treatment against retinal angiogenesis and edema. The purpose of this
      study was to evaluate whether intravitreal anti-VEGF Ab injection modulates
      inflammatory cells in retinal angiogenesis. METHODS: To investigate whether
      intravitreal bevacizumab injections affect the number of inflammatory cells in
      proliferative diabetic retinopathy (PDR) membranes in patients,
      immunohistochemical staining with CD45 Ab (pan-leukocyte marker) was performed
      using the surgically obtained membranes in pars plana vitrectomy with or without
      pretreatment with bevacizumab. To check whether anti-VEGF-A Ab affects leukocytes
      going in and out of blood vessels during retinal angiogenesis, the authors
      performed their novel leukocyte transmigration assay and CD45 immunostaining in a
      mouse model of oxygen-induced retinopathy (OIR). RESULTS: The authors' new
      imaging approach revealed that intravitreal injection of anti-VEGF-A Ab blocks
      leukocyte infiltration as well as angiogenesis. The Ab injection inhibited
      leukocyte transmigration before affecting the angiogenenic area. CD45 staining
      showed no significant difference in the leukocyte number in the angiogenic retina
      or the human PDR membranes between the anti-VEGF-A Ab injected group and the
      control group. Furthermore, VEGF-A inhibition also affected leukocytes going out
      from the retina. CONCLUSIONS: Intravitreal injection of anti-VEGF-A Ab could
      inhibit leukocyte trafficking in the retina, suggesting that anti-VEGF-A therapy
      could serve as a treatment in retinal inflammation.

PMID- 22661477
TI  - Comparison of choroidal and optic nerve head blood flow regulation during changes
      in ocular perfusion pressure.
AB  - PURPOSE: We compared the response of choroidal and optic nerve head blood flow
      (ChBF, ONHBF) in response to an increase in ocular perfusion pressure (OPP)
      during isometric exercise and during a decrease in OPP during an artificial
      increase in intraocular pressure (IOP). METHODS: We included 96 healthy subjects
      in our study. In 48 subjects OPP was increased by 6 minutes of squatting, and
      either ONHBF (n = 24) or ChBF (n = 24) was measured continuously. In 48 other
      healthy subjects either ONHBF (n = 24) or ChBF (n = 24) was measured continuously
      during a period of artificial increase in IOP using a suction cup. All blood flow
      measurements were done using laser Doppler flowmetry. RESULTS: During all
      experiments the response in blood flow was less pronounced than the response in
      OPP, indicating for flow regulation. During isometric exercise ChBF regulated
      better than ONHBF (P = 0.023). During artificial IOP increase ONHBF regulated
      better than ChBF (P = 0.001). Inter-individual variability in blood flow
      responses was high. During squatting ONHBF decreased considerably below baseline
      ONHBF when OPP fluctuated in 3 subjects, although OPP still was much higher than
      at baseline. This phenomenon was not observed in the choroid. CONCLUSIONS: Our
      data indicate that regulation of ChBF and ONHBF during changes in OPP is
      different and complex. In some subjects performing squatting, considerable ONHBF
      reductions were observed during OPP fluctuations, although OPP still was high.
      Whether this predisposes to ocular disease remains unclear.

PMID- 22661478
TI  - Efficacy of intravitreal administrations of linezolid in an experimental model of
      S. aureus-related endophthalmitis.
AB  - PURPOSE: To evaluate the efficacy of intravitreal administration of linezolid
      (LZD) in a rabbit model of Staphylococcus aureus endophthalmitis. METHODS: Of 40
      rabbits studied, 36 of them received 10(2) colony-forming units (CFU) of S.
      aureus in their right eye before being randomly assigned to the following groups:
      four groups of 8 animals received 24 hours after the bacterial inoculation, 1,
      10, 30 mg of LZD (LZD 1, LZD 10, and LZD 30) or 1 mg of vancomycin (V1),
      respectively. Four other animals had a sham injection in their infected eye. The
      4 remaining animals were used as negative controls. Clinical, bacterial, and
      histologic assessments were conducted at different endpoints. Animals were
      euthanized at day 8. The safety profile of intravitreal LZD was assessed by
      electroretinography in 5 more animals by comparing the recordings in eyes
      injected with 30 mg of LZD and contralateral control eyes injected with a
      solution of sterile saline water. RESULTS: At day 5, the mean inflammatory
      clinical scores of Nussenblatt were 7.0 +/- 1.0, 3.6 +/- 0.7, and 3.1 +/- 0.8, in
      the LZD 1, LZD 10, and LZD 30 groups and 3.4 +/- 1.7 and 7.5 +/- 0 in the V1 and
      BSS+ groups, respectively (P < 0.05, ANOVA). The corresponding mean bacterial
      counts in the vitreous (log 10 CFU/mL) were 6.2 +/- 6.5, 3.5 +/- 3.8, 0, 3.8 +/-
      4.2, and 7.8 +/- 4.9, respectively (P < 0.05, ANOVA). A 30 mg dose of LZD
      sterilized all the eyes at day 5 and displayed the lowest (best) histologic score
      (1.5 +/- 0.6). Residual LZD concentrations 24 hours after the administration were
      between 0.1 and 7.2 mg/L LZD 30 group. The half-time of linezolid in the vitreous
      was 2 hours. There were no differences in the electroretinogram recordings
      between control eyes and eyes injected with 30 mg of linezolid at days 1 and 14
      after the intravitreal injection. CONCLUSIONS: This is the first evidence of the
      effectiveness of linezolid for the treatment of experimental staphylococcal
      endophthalmitis. High ocular concentrations of LZD were needed to obtain a
      satisfactory bactericidal effect. Linezolid displayed a concentration-dependent
      killing activity in the eye. Such doses of intravitreal linezolid appeared to be
      safe for the retinal function.

PMID- 22661479
TI  - Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in
      family-based and case-control studies.
AB  - PURPOSE: Keratoconus is a bilateral noninflammatory progressive corneal disorder
      with complex genetic inheritance and a common cause for cornea transplantation in
      young adults. A genomewide linkage scan in keratoconus families identified a
      locus at 5q23.2, overlapping the gene coding for the lysyl oxidase (LOX). LOX
      encodes an enzyme responsible for collagen cross-linking in a variety of tissues
      including the cornea. Corneal collagen cross-linking with long-wave ultraviolet
      light and riboflavin is a promising new treatment for keratoconus. To determine
      whether LOX is a genetic determinant of the pathogenesis of keratoconus, we
      analyzed association results of LOX polymorphisms in two independent case-control
      samples and in keratoconus families. METHODS: Association results were analyzed
      of single-nucleotide polymorphisms (SNPs) in the LOX gene from a Genome-Wide
      Association Study (GWAS) investigation in two independent panels of patients with
      keratoconus and controls and in keratoconus families. RESULTS: Evidence of
      association was found at SNPs rs10519694 and rs2956540 located in intron 4 of LOX
      in the GWAS discovery case-control panel with P values of 2.3*10(-3) and 7*10(
      3), respectively. The same two SNPs were found to be associated with keratoconus
      by family-based association testing with P values of 2.7*10(-3) and 7.7*10(-4),
      respectively. Meta P values of 4.0*10(-5) and 4.0*10(-7) were calculated for SNPs
      rs10519694 and rs2956540 by analyzing case-control and family samples
      simultaneously. Sequencing of LOX exons in a subset of keratoconus patients
      identified two polymorphisms, rs1800449 and rs2288393, located in LOX transcripts
      I and II, associated with keratoconus in case-control and family samples with a
      meta P value of 0.02. CONCLUSIONS: Results provided strong genetic evidence that
      LOX variants lead to increased susceptibility to developing of keratoconus.

PMID- 22661481
TI  - A phage display-based approach to investigate abnormal neovessels of the retina.
AB  - PURPOSE: The goal of this project was to identify markers of abnormal
      neovascularization of the retinal vasculature, which is quintessential of
      pathologic angiogenesis that occurs in blinding diseases such as proliferative
      diabetic retinopathy. METHODS: Abnormal retinal neovascularization was induced in
      rat pups by subjecting them to the 50/10 oxygen-induced retinopathy (OIR)
      protocol, which involves fluctuating levels of ambient oxygen. A peptide library
      (that was displayed on phage) was positively and negatively screened over the
      surface of retinas isolated from experimental and control rats, respectively.
      Binding of phage to retinal vessels was evaluated by confocal microscopy of
      retinal flat mounts decorated with fluorescently labeled phage. The topography of
      the inner limiting membrane was studied by scanning electron microscopy. RESULTS:
      Screening a library of peptides displayed on phage over the surface of OIR
      retinas resulted in isolation of a particular phage (SH phage) that distinguished
      between abnormal neovessels and the normal vasculature. As expected, the
      recognition of abnormal neovessels relied on the unique peptide insert of SH
      phage. Abnormal neovessels consisted of at least three cell types that were
      present in the following order of descending abundance: endothelial > pericytes >
      macrophage/microglia. SH phage recognized both endothelial cells and
      macrophage/microglia. Finally, SH phage decorated abnormal neovessels at an early
      stage of their genesis. CONCLUSIONS: Abnormal development of neovessels is
      associated with early expression of distinct epitopes on the surface of cells
      within the pathologic vasculature. Screening phage display libraries is one
      approach to detecting such changes, and the resulting phage are potential imaging
      tools and/or drug delivery vehicles.

PMID- 22661480
TI  - Silk fibroin as a biomaterial substrate for corneal epithelial cell sheet
      generation.
AB  - PURPOSE: To evaluate a silk fibroin (SF) biomaterial as a substrate for corneal
      epithelial cell proliferation, differentiation, and stratification in vitro
      compared with denuded human amniotic membrane (AM). METHODS: Primary human and
      rabbit corneal epithelial cells and immortalized human corneal limbal epithelial
      cells were cultured on the SF and denuded AM, respectively. The biological cell
      behavior, including the morphology, proliferation, differentiation, and
      stratification, on the two substrates was compared and analyzed. RESULTS: Corneal
      epithelial cells can adhere and proliferate on the SF and denuded AM with a
      cobblestone appearance, abundant microvilli on the surface, and wide connection
      with the adjacent cells. MTT assay showed that cell proliferation on denuded AM
      was statistically higher than that on SF at 24 and 72 hours after plating (P =
      0.001 and 0.0005, respectively). Expression of DeltaNp63a and keratin 3/12 was
      detected in primary cell cultures on the two substrates with no statistical
      difference. When cultured at the air-liquid interface for 7 days, cells on SF
      could form a comparable stratified graft with a 2- to 3-cell layering, which
      compared similarly to AM cultures. CONCLUSIONS: SF, a novel biomaterial, could
      support corneal epithelial cells to proliferate, differentiate, and stratify,
      retaining the normal characteristic epithelium phenotype. Compared with AM, its
      unique features, including the transparency, ease of handling, and transfer, and
      inherent freedom from disease transmission, make it a promising substrate for
      corneal wound repair and tissue-engineering purposes.

PMID- 22661482
TI  - Quantitative analysis of retinal vessel attenuation in eyes with retinitis
      pigmentosa.
AB  - PURPOSE: Retinal vessel attenuation is a key finding in the diagnosis of
      retinitis pigmentosa (RP), but there have been no studies to determine whether
      quantitative measurement of this retinal sign is useful. We aimed to investigate
      retinal vessel caliber and its relationship with the severity of RP. METHODS:
      This is a cross-sectional study based on 74 patients (145 eyes) with RP who had
      visual field assessment with Goldmann permeter and good-quality retinal images
      for vessel size measurements identified by retrospective medial chart review
      (1973-2007) in the electrophysiology clinic of a tertiary eye hospital in
      Australia. Retinal vessel calibers were measured using a computer-based program
      as the central retinal artery and vein equivalent (CRAE and CRVE). Goldmann
      visual field area for III4e white test light was measured quantitatively using
      ImageJ software as a clinical parameter to indicate the severity of RP. We used
      the generalized estimating equation models to estimate the difference in retina
      vessel calibers accounting for correlation between right and left eyes. RESULTS:
      Mean CRAE and CRVE were significantly narrower in persons with smaller visual
      field area. For each 100 cm2 decrease in visual field area, CRAE and CRVE
      decreased by -15.2 MUm (95% confidence interval -20.7, -9.78) and -26.8 MUm (
      35.1, -18.5), respectively (both P<0.001). CONCLUSIONS: In RP patients, the
      severity of visual field loss is correlated with retinal vessel attenuation.
      Quantitative retinal vessel caliber measurement may be a useful additional
      clinical marker for monitoring progression of RP or potential treatment response.

PMID- 22661483
TI  - Topography of geographic atrophy in age-related macular degeneration.
AB  - PURPOSE: To determine the topographic distribution and progression of geographic
      atrophy (GA) in patients with AMD. METHODS: Fundus autofluorescence images
      (excitation 488, emission 500-700 nm) from 413 eyes of 413 subjects (median age,
      77.0 years; inter quartile range [IQR], 72.0-82.0 years) of the Geographic
      Atrophy Progression (GAP) study were retrospectively analyzed. Using a modified
      Early Treatment Diabetic Retinopathy Study grid to divide the posterior pole into
      nine different subfields plus periphery, the localization, size, and progression
      of atrophic patches were determined. Subfields, zones (center, inner and outer),
      and slices (nasal, temporal, inferior, superior) were compared using the Friedman
      test. RESULTS: The center and inner zones were involved in almost all eyes
      (>95%), while atrophy was less common in the outer zone subfields (76%). Inner
      zone atrophy size (median 4.00 mm(2)) and progression rate (0.67 mm(2)/year) were
      significantly greater than in the outer zone (0.60 mm(2) and 0.42 mm(2)/year; P <
      0.001). There was a trend toward outer zone subfield and periphery involvement
      with increasing total size of atrophy. In addition, the superior outer subfield
      was significantly more affected by atrophy as compared with the other three outer
      subfields of the grid (P < 0.001). CONCLUSIONS: Distribution and progression of
      existing GA patches depended both on the eccentricity from the center and total
      GA size. Central macular areas appeared most susceptible for the occurrence and
      expansion of GA. Refined analysis of distribution and directional spread is
      important to understand the natural history of the disease. This information will
      likely be helpful to design interventional GA clinical trials and associated
      anatomical outcome measures. (ClinicalTrials. gov number, NCT00599846.).

PMID- 22661484
TI  - Pharmacologic induction of heme oxygenase-1 plays a protective role in diabetic
      retinopathy in rats.
AB  - PURPOSE: We investigated the protective effects of HO-1, induced by hemin, in the
      retinas of streptozotocin (STZ)-induced diabetic rats, and document the possible
      anti-inflammatory, anti-apoptotic, and anti-proliferative mechanisms underlying
      the protection. METHODS: Sprague-Dawley (SD) rats were induced to diabetes by
      intraperitoneal injection of STZ (60 mg/kg). Later, some of the rats were given
      intraperitoneal injections of hemin (20 mg/kg) to induce expression of HO-1. The
      protective effects of hemin were evaluated by examining the hemoglobin
      concentration (Hb) and the glycosylated hemoglobin (HbA1c) level of blood from
      the rats, further calculating the numbers of TUNEL positive cells in retinal
      ganglion cell (RGC) layer and diI-labeled RGCs. We also documented the
      expressions of HO-1, HIF-1alpha, SOD-1, VEGF, p53, and bcl-2 by Western blot
      analysis and real-time quantitative PCR. Expressions of Nrf2, tERK 1/2, and pERK
      1/2 were detected only by Western blot analysis. HO-1, Nrf2, pERK, and GFAP
      proteins were detected by immunofluorescence. RESULTS: The Hb level was higher in
      hemin-treated rat blood than nontreated diabetic group, while the HbA1c level was
      lower. Hemin significantly activated HO-1 expression in the retinas of diabetic
      rats, combined with accordant changes of Nrf2/pERK protein expression, and
      upregulated the expression of GFAP in retina. Retinal ganglion cells displayed
      greater sensitivity to apoptosis when the HO-1 level was lower. Overexpression of
      HO-1 was associated with an increase in the activation of SOD-1 and bcl-2, and a
      decrease of the expression of HIF-1alpha, VEGF, and p53. CONCLUSIONS: HO-1 is an
      important positive modulator of the Nrf2/ERK-related signaling. Overexpression of
      HO-1 by hemin induction protected retinal ganglion cells in diabetic retinopathy
      through anti-inflammatory, anti-apoptotic, and anti-proliferative effects.

PMID- 22661485
TI  - Standardized assessment of reading performance: the New International Reading
      Speed Texts IReST.
AB  - PURPOSE: There is a need for standardized texts to assess reading performance,
      for multiple equivalent texts for repeated measurements, and for texts equated
      across languages for multi-language studies. Paragraphs are preferable to single
      sentences for accurate speed measurement. We developed such texts previously in 6
      languages. The aim of our current study was to develop texts in more languages
      for a wide range of countries and users, and to assess the reading speeds of
      normally-sighted readers. METHODS: Ten texts were designed for 17 languages each
      by a linguist who matched content, length, difficulty, and linguistic complexity.
      The texts then were used to assess reading speeds of 436 normally-sighted native
      speakers (age 18-35 years, 25 per language, 36 in Japanese), presented at a
      distance of 40 cm and size 1 M, that is 10-point Times New Roman font. Reading
      time (aloud) was measured by stopwatch. RESULTS: For all 17 languages, average
      mean reading speed was 1.42 +/- 0.13 texts/min (+/-SD), 184 +/- 29 words/min, 370
      +/- 80 syllables/min, and 863 +/- 234 characters/min. For 14 languages, mean
      reading time was 68 ms/character (95% confidence interval [CI] 65-71 ms). Our
      analysis focussed on words per minute. The variability of reading speed within
      subjects accounts only for an average of 11.5%, between subjects for 88.5%.
      CONCLUSIONS: The low within-subject variability shows the equivalence of the
      texts. The IReST (second edition) can now be provided in 17 languages allowing
      standardized assessment of reading speed, as well as comparability of results
      before and after interventions, and is a useful tool for multi-language studies
      (for further information see www.amd-read.net).

PMID- 22661487
TI  - Letter to the editor: Measurement of autophagy-related proteins by
      immunohistochemistry/tissue microarray to characterize autophagy: problems and
      considerations.

PMID- 22661486
TI  - Genome-wide analysis of central corneal thickness in primary open-angle glaucoma
      cases in the NEIGHBOR and GLAUGEN consortia.
AB  - PURPOSE: To investigate the effects of central corneal thickness (CCT)-associated
      variants on primary open-angle glaucoma (POAG) risk using single nucleotide
      polymorphisms (SNP) data from the Glaucoma Genes and Environment (GLAUGEN) and
      National Eye Institute (NEI) Glaucoma Human Genetics Collaboration (NEIGHBOR)
      consortia. METHODS: A replication analysis of previously reported CCT SNPs was
      performed in a CCT dataset (n = 1117) and these SNPs were then tested for
      association with POAG using a larger POAG dataset (n = 6470). Then a CCT genome
      wide association study (GWAS) was performed. Top SNPs from this analysis were
      selected and tested for association with POAG. cDNA libraries from fetal and
      adult brain and ocular tissue samples were generated and used for candidate gene
      expression analysis. RESULTS: Association with one of 20 previously published CCT
      SNPs was replicated: rs12447690, near the ZNF469 gene (P = 0.001; beta = -5.08
      MUm/allele). None of these SNPs were significantly associated with POAG. In the
      CCT GWAS, no SNPs reached genome-wide significance. After testing 50 candidate
      SNPs for association with POAG, one SNP was identified, rs7481514 within the
      neurotrimin (NTM) gene, that was significantly associated with POAG in a low
      tension subset (P = 0.00099; Odds Ratio [OR] = 1.28). Additionally, SNPs in the
      CNTNAP4 gene showed suggestive association with POAG (top SNP = rs1428758; P =
      0.018; OR = 0.84). NTM and CNTNAP4 were shown to be expressed in ocular tissues.
      CONCLUSIONS: The results suggest previously reported CCT loci are not
      significantly associated with POAG susceptibility. By performing a quantitative
      analysis of CCT and a subsequent analysis of POAG, SNPs in two cell adhesion
      molecules, NTM and CNTNAP4, were identified and may increase POAG susceptibility
      in a subset of cases.

PMID- 22661490
TI  - Common variation in fatty acid genes and resuscitation from sudden cardiac
      arrest.
AB  - BACKGROUND: Fatty acids provide energy and structural substrates for the heart
      and brain and may influence resuscitation from sudden cardiac arrest (SCA). We
      investigated whether genetic variation in fatty acid metabolism pathways was
      associated with SCA survival. METHODS AND RESULTS: Subjects (mean age, 67 years;
      80% male, white) were out-of-hospital SCA patients found in ventricular
      fibrillation in King County, WA. We compared subjects who survived to hospital
      admission (n=664) with those who did not (n=689), and subjects who survived to
      hospital discharge (n=334) with those who did not (n=1019). Associations between
      survival and genetic variants were assessed using logistic regression adjusting
      for age, sex, location, time to arrival of paramedics, whether the event was
      witnessed, and receipt of bystander cardiopulmonary resuscitation. Within-gene
      permutation tests were used to correct for multiple comparisons. Variants in 5
      genes were significantly associated with SCA survival. After correction for
      multiple comparisons, single-nucleotide polymorphisms in ACSL1 and ACSL3 were
      significantly associated with survival to hospital admission. Single-nucleotide
      polymorphisms in ACSL3, AGPAT3, MLYCD, and SLC27A6 were significantly associated
      with survival to hospital discharge. CONCLUSIONS: Our findings indicate that
      variants in genes important in fatty acid metabolism are associated with SCA
      survival in this population.

PMID- 22661491
TI  - Mechanistic evaluation of echocardiographic dyssynchrony indices: patient data
      combined with multiscale computer simulations.
AB  - BACKGROUND: The power of echocardiographic dyssynchrony indices to predict
      response to cardiac resynchronization therapy (CRT) appears to vary between
      indices and between studies. We investigated whether the variability of
      predictive power between the dyssynchrony indices can be explained by differences
      in their operational definitions. METHODS AND RESULTS: In 132 CRT-candidates
      (left ventricular [LV] ejection fraction, 19 +/- 6%; QRS width, 170 +/- 22 ms), 4
      mechanical dyssynchrony indices (septal systolic rebound stretch [SRSsept],
      interventricular mechanical dyssynchrony [IVMD], septal-to-lateral peak
      shortening delay [Strain-SL], and septal-to-posterior wall motion delay [SPWMD])
      were quantified at baseline. CRT response was quantified as 6-month percent
      change of LV end-systolic volume. Multiscale computer simulations of cardiac
      mechanics and hemodynamics were used to assess the relationships between
      dyssynchrony indices and CRT response within wide ranges of dyssynchrony of LV
      activation and reduced contractility. In patients, SRSsept showed best
      correlation with CRT response followed by IVMD, Strain-SL, and SPWMD (R=-0.56, 
      0.50, -0.48, and -0.39, respectively; all P<0.01). In patients and simulations,
      SRSsept and IVMD showed a continuous linear relationship with CRT response,
      whereas Strain-SL and SPWMD showed discontinuous relationships characterized by
      data clusters. Model simulations revealed that this data clustering originated
      from the complex multipeak pattern of septal strain and motion. In patients and
      simulations with (simulated) LV scar, SRSsept and IVMD retained their linear
      relationship with CRT response, whereas Strain-SL and SPWMD did not. CONCLUSIONS:
      The power to predict CRT response differs between indices of mechanical
      dyssynchrony. SRSsept and IVMD better represent LV dyssynchrony amenable to CRT
      and better predict CRT response than the indices assessing time-to-peak
      deformation or motion.

PMID- 22661492
TI  - Weaning diet induces sustained metabolic phenotype shift in the pig and
      influences host response to Bifidobacterium lactis NCC2818.
AB  - BACKGROUND: The process of weaning causes a major shift in intestinal microbiota
      and is a critical period for developing appropriate immune responses in young
      mammals. OBJECTIVE: To use a new systems approach to provide an overview of host
      metabolism and the developing immune system in response to nutritional
      intervention around the weaning period. DESIGN: Piglets (n=14) were weaned onto
      either an egg-based or soya-based diet at 3 weeks until 7 weeks, when all piglets
      were switched onto a fish-based diet. Half the animals on each weaning diet
      received Bifidobacterium lactis NCC2818 supplementation from weaning onwards.
      Immunoglobulin production from immunologically relevant intestinal sites was
      quantified and the urinary (1)H NMR metabolic profile was obtained from each
      animal at post mortem (11 weeks). RESULTS: Different weaning diets induced
      divergent and sustained shifts in the metabolic phenotype, which resulted in the
      alteration of urinary gut microbial co-metabolites, even after 4 weeks of dietary
      standardisation. B lactis NCC2818 supplementation affected the systemic
      metabolism of the different weaning diet groups over and above the effects of
      diet. Additionally, production of gut mucosa-associated IgA and IgM was found to
      depend upon the weaning diet and on B lactis NCC2818 supplementation. CONCLUSION:
      The correlation of urinary (1)H NMR metabolic profile with mucosal immunoglobulin
      production was demonstrated, thus confirming the value of this multi-platform
      approach in uncovering non-invasive biomarkers of immunity. This has clear
      potential for translation into human healthcare with the development of urine
      testing as a means of assessing mucosal immune status. This might lead to early
      diagnosis of intestinal dysbiosis and with subsequent intervention, arrest
      disease development. This system enhances our overall understanding of
      pathologies under supra-organismal control.

PMID- 22661489
TI  - Improved neuropsychological and neurological functioning across three
      antiretroviral regimens in diverse resource-limited settings: AIDS Clinical
      Trials Group study a5199, the International Neurological Study.
AB  - BACKGROUND: AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and
      neuropsychological (NP) effects of 3 antiretroviral regimens in participants
      infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited
      settings. METHODS: Participants from Brazil, India, Malawi, Peru, South Africa,
      Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A
      (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine,
      and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate
      plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized
      neurological and neuropsychological (NP) screening examinations (grooved
      pegboard, timed gait, semantic verbal fluency, and finger tapping) were
      administered every 24 weeks from February 2006 to May 2010. Associations with
      neurological and neuropsychological function were estimated from linear and
      logistic regression models using generalized estimating equations. RESULTS: The
      median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP
      test scores improved (P < .05) with the exception of semantic verbal fluency. No
      differences in neurological and neuropsychological functioning between treatment
      regimens were detected (P > .10). Significant country effects were noted on all
      NP tests and neurological outcomes (P < .01). CONCLUSIONS: The study detected no
      significant differences in neuropsychological and neurological outcomes between
      randomized ART regimens. Significant improvement occurred in neurocognitive and
      neurological functioning over time after initiation of ARTs. The etiology of
      these improvements is likely multifactorial, reflecting reduced central nervous
      system HIV infection, better general health, and practice effects. This study
      suggests that treatment with either of the World Health Organization -recommended
      first-line antiretroviral regimens in resource-limited settings will improve
      neuropsychological functioning and reduce neurological dysfunction. CLINICAL
      TRIALS REGISTRATION: NCT00096824.

PMID- 22661493
TI  - Brain-gut interactions in the regulation of satiety: new insights from functional
      brain imaging.

PMID- 22661494
TI  - A rare cause of dysphagia.

PMID- 22661495
TI  - Bacterial infections in end-stage liver disease: current challenges and future
      directions.

PMID- 22661496
TI  - Improving drug delivery to pancreatic cancer: breaching the stromal fortress by
      targeting hyaluronic acid.

PMID- 22661497
TI  - Functional (conversion) neurological symptoms: research since the millennium.
AB  - Functional neurological symptoms (FNS) are commonly encountered but have
      engendered remarkably little academic interest. 'UK-Functional Neurological
      Symptoms (UK-FNS)' was an informal inaugural meeting of UK based clinicians in
      March 2011 with a variety of research and clinical interests in the field. This
      narrative review reflects the content of the meeting, and our opinion of key
      findings in the field since the turn of the millennium.

PMID- 22661499
TI  - The spectrum of mutations that underlie the neuromuscular junction synaptopathy
      in DOK7 congenital myasthenic syndrome.
AB  - Congenital myasthenic syndromes (CMS) are a group of inherited diseases that
      affect synaptic transmission at the neuromuscular junction and result in
      fatiguable muscle weakness. A subgroup of CMS patients have a recessively
      inherited limb-girdle pattern of weakness caused by mutations in DOK7. DOK7
      encodes DOK7, an adaptor protein that is expressed in the skeletal muscle and
      heart and that is essential for the development and maintenance of the
      neuromuscular junction. We have screened the DOK7 gene for mutations by
      polymerase chain reaction amplification and bi-directional sequencing of exonic
      and promoter regions and performed acetylcholine receptor (AChR) clustering
      assays and used exon trapping to determine the pathogenicity of detected
      variants. Approximately 18% of genetically diagnosed CMSs in the UK have
      mutations in DOK7, with mutations in this gene identified in more than 60
      kinships to date. Thirty-four different pathogenic mutations were identified as
      well as 27 variants likely to be non-pathogenic. An exon 7 frameshift duplication
      c.1124_1127dupTGCC is commonly found in at least one allele. We analyse the
      effect of the common frameshift c.1124_1127dupTGCC and show that 10/11 suspected
      missense mutations have a deleterious effect on AChR clustering. We identify for
      the first time homozygous or compound heterozygous mutations that are localized
      5' to exon 7. In addition, three silent variants in the N-terminal half of DOK7
      are predicted to alter the splicing of the DOK7 RNA transcript. The DOK7 gene is
      highly polymorphic, and within these many variants, we define a spectrum of
      mutations that can underlie DOK7 CMS that will inform in managing this disorder.

PMID- 22661498
TI  - Cardiovascular remodeling in response to long-term exposure to fine particulate
      matter air pollution.
AB  - BACKGROUND: Air pollution is a pervasive environmental health hazard that occurs
      over a lifetime of exposure in individuals from many industrialized societies.
      However, studies have focused primarily on exposure durations that correspond to
      only a portion of the lifespan. We therefore tested the hypothesis that exposure
      over a considerable portion of the lifespan would induce maladaptive
      cardiovascular responses. METHODS AND RESULTS: C57BL/6 male mice were exposed to
      concentrated ambient particles <2.5 um (particulate matter, PM or PM(2.5)) or
      filtered air (FA), 6 h/d, 5 d/wk, for 9 months. Assessment of cardiac contractile
      function, coronary arterial flow reserve, isolated cardiomyocyte function,
      expression of hypertrophic markers, calcium handling proteins, and cardiac
      fibrosis were then performed. Mean daily concentrations of PM(2.5) in the
      exposure chamber versus ambient daily PM(2.5) concentration at the study site
      were 85.3 versus 10.6 ug/m(3) (7.8-fold concentration), respectively. PM(2.5)
      exposure resulted in increased hypertrophic markers leading to adverse
      ventricular remodeling characterized by myosin heavy chain (MHC) isoform switch
      and fibrosis, decreased fractional shortening (39.8 +/- 1.4 FA versus 27.9 +/-
      1.3 PM, FS%), and mitral inflow patterns consistent with diastolic dysfunction
      (1.95 +/- 0.05 FA versus 1.52 +/- 0.07 PM, E/A ratio). Contractile reserve to
      dobutamine was depressed (62.3 +/- 0.9 FA versus 49.2 +/- 1.5 PM, FS%) in
      response to PM(2.5) without significant alterations in maximal vasodilator flow
      reserve. In vitro cardiomyocyte function revealed depressed peak shortening (8.7
      +/- 0.6 FA versus 7.0 +/- 0.4 PM, %PS) and increased time-to-90% shortening (72.5
      +/- 3.2 FA versus 82.8 +/- 3.2 PM, ms) and re-lengthening (253.1 +/- 7.9 FA
      versus 282.8 +/- 9.3 PM, ms), which were associated with upregulation of
      profibrotic markers and decreased total antioxidant capacity. Whole-heart SERCA2a
      levels and the ratio of alpha/beta-MHC were both significantly decreased (P<0.05)
      in PM(2.5)-exposed animals, suggesting a switch to fetal programming.
      CONCLUSIONS: Long-term exposure to environmentally relevant concentrations of
      PM(2.5) resulted in a cardiac phenotype consistent with incipient heart failure.

PMID- 22661500
TI  - Evidence for premature aging due to oxidative stress in iPSCs from Cockayne
      syndrome.
AB  - Cockayne syndrome (CS) is a human premature aging disorder associated with
      neurological and developmental abnormalities, caused by mutations mainly in the
      CS group B gene (ERCC6). At the molecular level, CS is characterized by a
      deficiency in the transcription-couple DNA repair pathway. To understand the role
      of this molecular pathway in a pluripotent cell and the impact of CSB mutation
      during human cellular development, we generated induced pluripotent stem cells
      (iPSCs) from CSB skin fibroblasts (CSB-iPSC). Here, we showed that the lack of
      functional CSB does not represent a barrier to genetic reprogramming. However,
      iPSCs derived from CSB patient's fibroblasts exhibited elevated cell death rate
      and higher reactive oxygen species (ROS) production. Moreover, these cellular
      phenotypes were accompanied by an up-regulation of TXNIP and TP53 transcriptional
      expression. Our findings suggest that CSB modulates cell viability in pluripotent
      stem cells, regulating the expression of TP53 and TXNIP and ROS production.

PMID- 22661501
TI  - A persistent level of Cisd2 extends healthy lifespan and delays aging in mice.
AB  - The CISD2 gene, which is an evolutionarily conserved novel gene, encodes a
      transmembrane protein primarily associated with the mitochondrial outer membrane.
      Significantly, the CISD2 gene is located within the candidate region on
      chromosome 4q where a genetic component for human longevity has been mapped.
      Previously, we have shown that Cisd2 deficiency shortens lifespan resulting in
      premature aging in mice. Additionally, an age-dependent decrease in Cisd2
      expression has been detected during normal aging. In this study, we demonstrate
      that a persistent level of Cisd2 achieved by transgenic expression in mice
      extends their median and maximum lifespan without any apparent deleterious side
      effects. Cisd2 also ameliorates age-associated degeneration of the skin, skeletal
      muscles and neurons. Moreover, Cisd2 protects mitochondria from age-associated
      damage and functional decline as well as attenuating the age-associated reduction
      in whole-body energy metabolism. These results suggest that Cisd2 is a
      fundamentally important regulator of lifespan and provide an experimental basis
      for exploring the candidacy of CISD2 in human longevity.

PMID- 22661502
TI  - On "Emergence of delayed posttraumatic stress disorder symptoms..." Dunleavy K,
      Kubo Slowik A. Phys Ther. 2012;92:339-351.

PMID- 22661504
TI  - On "PTJ adopts a new process for review of RCTs" [editorial]. Craik RL. Phys
      Ther. 2012;92:642-643.

PMID- 22661506
TI  - Epigenetic upregulation of p66shc mediates low-density lipoprotein cholesterol
      induced endothelial cell dysfunction.
AB  - Hypercholesterolemia characterized by elevation of low-density lipoprotein (LDL)
      cholesterol is a major risk factor for atherosclerotic vascular disease. p66shc
      mediates hypercholesterolemia-induced endothelial dysfunction and atheromatous
      plaque formation. We asked if LDL upregulates endothelial p66shc via changes in
      the epigenome and examined the role of p66shc in LDL-stimulated endothelial cell
      dysfunction. Human LDL stimulates human p66shc promoter activity and p66shc
      expression in human endothelial cells. LDL leads to hypomethylation of two CpG
      dinucleotides and acetylation of histone 3 in the human p66shc promoter. These
      two CpG dinucleotides mediate LDL-stimulated p66shc promoter activity. Inhibition
      or knock down of DNA methyltransferases negates LDL-induced endothelial p66shc
      expression. p66shc mediates LDL-stimulated increase in expression of endothelial
      intercellular adhesion molecule-1 (ICAM1) and decrease in expression of
      thrombomodulin (TM). Mirroring these changes in ICAM1 and TM expression, p66shc
      mediates LDL-stimulated adhesion of monocytes to endothelial cells and plasma
      coagulation on endothelial cells. These findings indicate that LDL cholesterol
      upregulates human endothelial p66shc expression via hypomethylation of CpG
      dinucleotides in the p66shc promoter. Moreover, they show that LDL-stimulated
      p66shc expression mediates a dysfunctional endothelial cell surface, with
      proadhesive and procoagulant features.

PMID- 22661507
TI  - Effect of healthy aging on left ventricular relaxation and diastolic suction.
AB  - Doppler ultrasound measures of left ventricular (LV) active relaxation and
      diastolic suction are slowed with healthy aging. It is unclear to what extent
      these changes are related to alterations in intrinsic LV properties and/or
      cardiovascular loading conditions. Seventy carefully screened individuals (38
      female, 32 male) aged 21-77 were recruited into four age groups (young: <35;
      early middle age: 35-49; late middle age: 50-64 and seniors: >=65 yr). Pulmonary
      capillary wedge pressure (PCWP), stroke volume, LV end-diastolic volume, and
      Doppler measures of LV diastolic filling were collected at multiple loading
      conditions, including supine baseline, lower body negative pressure to reduce LV
      filling, and saline infusion to increase LV filling. LV mass, supine PCWP, and
      heart rate were not affected significantly by aging. Measures of LV relaxation,
      including isovolumic relaxation time and the time constant of isovolumic pressure
      decay increased progressively, whereas peak early mitral annular longitudinal
      velocity decreased with advancing age (P < 0.001). The propagation velocity of
      early mitral inflow, a noninvasive measure of LV suction, decreased with aging
      with the greatest reduction in seniors (P < 0.001). Age-related differences in LV
      relaxation and diastolic suction were not attenuated significantly when PCWP was
      increased in older subjects or reduced in the younger subjects. There is an early
      slowing of LV relaxation and diastolic suction beginning in early middle age,
      with the greatest reduction observed in seniors. Because age-related differences
      in LV dynamic diastolic filling parameters were not diminished significantly with
      significant changes in LV loading conditions, a decline in ventricular relaxation
      is likely responsible for the alterations in LV diastolic filling with
      senescence.

PMID- 22661508
TI  - Statin therapy lowers muscle sympathetic nerve activity and oxidative stress in
      patients with heart failure.
AB  - Despite standard drug therapy, sympathetic nerve activity (SNA) remains high in
      heart failure (HF) patients making the sympathetic nervous system a primary drug
      target in the treatment of HF. Studies in rabbits with pacing-induced HF have
      demonstrated that statins reduce resting SNA, in part, due to reductions in
      reactive oxygen species (ROS). Whether these findings can be extended to the
      clinical setting of human HF remains unclear. We first performed a study in seven
      statin-naive HF patients (56 +/- 2 yr; ejection fraction: 31 +/- 4%) to determine
      if 1 mo of simvastatin (40 mg/day) reduces muscle SNA (MSNA). Next, to control
      for possible placebo effects and determine the effect of simvastatin on ROS, a
      double-blinded, placebo-controlled crossover design study was performed in six
      additional HF patients (51 +/- 3 yr; ejection fraction: 22 +/- 4%), and MSNA,
      ROS, and superoxide were measured. We tested the hypothesis that statin therapy
      decreases resting MSNA in HF patients and this would be associated with
      reductions in ROS. In study 1, simvastatin reduced resting MSNA (75 +/- 5
      baseline vs. 65 +/- 5 statin bursts/100 heartbeats; P < 0.05). Likewise, in study
      2, simvastatin also decreased resting MSNA (59 +/- 5 placebo vs. 45 +/- 6 statin
      bursts/100 heartbeats; P < 0.05). In addition, statin therapy significantly
      reduced total ROS and superoxide. As expected, cholesterol was reduced after
      simvastatin. Collectively, these findings indicate that short-term statin therapy
      concomitantly reduces resting MSNA and total ROS and superoxide in HF patients.
      Thus, in addition to lowering cholesterol, statins may also be beneficial in
      reducing sympathetic overactivity and oxidative stress in HF patients.

PMID- 22661510
TI  - Unprovoked atrial tachyarrhythmias in aging spontaneously hypertensive rats: the
      role of the autonomic nervous system.
AB  - Experimental models of unprovoked atrial tachyarrhythmias (AT) in conscious,
      ambulatory animals are lacking. We hypothesized that the aging, spontaneously
      hypertensive rat (SHR) may provide such a model. Baseline ECG recordings were
      acquired with radiotelemetry in eight young (14-wk-old) and eight aging (55-wk
      old) SHRs and in two groups of four age-matched Wistar-Kyoto (WKY) rats.
      Quantification of AT and heart rate variability (HRV) analysis were performed
      based on 24-h ECG recordings in unrestrained rats. All animals were submitted to
      an emotional stress protocol (air-jet). In SHRs, carbamylcholine injections were
      also performed. Spontaneous AT episodes were observed in all eight aging SHRs
      (median, 91.5; range, 4-444 episodes/24 h), but not in young SHRs or WKY rats.
      HRV analysis demonstrated significantly decreased low frequency components in
      aging SHRs compared with age-matched WKY rats (P < 0.01) and decreased low/high
      frequency ratios in both young (P < 0.01) and aging (P = 0.01) SHRs compared with
      normotensive controls. In aging SHRs, emotional stress significantly reduced the
      number of arrhythmic events, whereas carbamylcholine triggered AT and
      significantly increased atrial electrical instability. This study reports the
      occurrence of unprovoked episodes of atrial arrhythmia in hypertensive rats, and
      their increased incidence with aging. Our results suggest that autonomic
      imbalance with relative vagal hyperactivity may be responsible for the increased
      atrial arrhythmogenicity observed in this model. We also provide evidence that,
      in this model, the sympatho-vagal imbalance preceded the occurrence of
      arrhythmia. These results indicate that aging SHRs may provide valuable insight
      into the understanding of atrial arrhythmias.

PMID- 22661509
TI  - Calcium alternans in a couplon network model of ventricular myocytes: role of
      sarcoplasmic reticulum load.
AB  - Intracellular calcium (Ca) alternans in cardiac myocytes have been shown in many
      experimental studies, and the mechanisms remain incompletely understood. We
      recently developed a "3R theory" that links Ca sparks to whole cell Ca alternans
      through three critical properties: randomness of Ca sparks; recruitment of a Ca
      spark by neighboring Ca sparks; and refractoriness of Ca release units. In this
      study, we used computer simulation of a physiologically detailed mathematical
      model of a ventricular myocyte couplon network to study how sarcoplasmic
      reticulum (SR) Ca load and other physiological parameters, such as ryanodine
      receptor sensitivity, SR uptake rate, Na-Ca exchange strength, and Ca buffer
      levels affect Ca alternans in the context of 3R theory. We developed a method to
      calculate the parameters used in the 3R theory (i.e., the primary spark rate and
      the recruitment rate) from the physiologically detailed Ca cycling model and
      paced the model periodically to elicit Ca alternans. We show that alternans only
      occurs for an intermediate range of the SR Ca load, and the underlying mechanism
      can be explained via its effects on the 3Rs. Furthermore, we show that altering
      the physiological parameters not only directly changes the 3Rs but also alters
      the SR Ca load, having an indirect effect on the 3Rs as well. Therefore, our
      present study links the SR Ca load and other physiological parameters to whole
      cell Ca alternans through the framework of the 3R theory, providing a general
      mechanistic understanding of Ca alternans in ventricular myocytes.

PMID- 22661511
TI  - Aldose reductase modulates cardiac glycogen synthase kinase-3beta phosphorylation
      during ischemia-reperfusion.
AB  - Earlier studies have demonstrated that aldose reductase (AR) plays a key role in
      mediating ischemia-reperfusion (I/R) injury. Our objective was to investigate if
      AR mediates I/R injury by influencing phosphorylation of glycogen synthase kinase
      3beta (p-GSK3beta). To investigate this issue, we used three separate models to
      study the effects of stress injury on the heart. Hearts isolated from wild-type
      (WT), human expressing AR transgenic (ARTg), and AR knockout (ARKO) mice were
      perfused with/without GSK3beta inhibitors (SB-216763 and LiCl) and subjected to
      I/R. Ad-human AR (Ad-hAR)-expressing HL-1 cardiac cells were exposed to hypoxia
      (0.5% O(2)) and reoxygenation (20.9% O(2)) conditions. I/R in a murine model of
      transient occlusion and reperfusion of the left anterior descending coronary
      artery (LAD) was used to study if p-GSK3beta was affected through increased AR
      flux. Lactate dehydrogenase (LDH) release and left ventricular developed pressure
      (LVDP) were measured. LVDP was decreased in hearts from ARTg mice compared with
      WT and ARKO after I/R, whereas LDH release and apoptotic markers were increased
      (P < 0.05). p-GSK3beta was decreased in ARTg hearts compared with WT and ARKO (P
      < 0.05). In ARKO, p-GSK3beta and apoptotic markers were decreased compared with
      WT (P < 0.05). WT and ARTg hearts perfused with GSK3beta inhibitors improved p
      GSK3beta expression and LVDP and exhibited decreased LDH release, apoptosis, and
      mitochondrial pore opening (P < 0.05). Ad-hAR-expressing HL-1 cardiac cells,
      exposed to hypoxia (0.5% O(2)) and reoxygenation (20.9% O(2)), had greater LDH
      release compared with control HL-1 cells (P < 0.05). p-GSK3beta was decreased and
      correlated with increased apoptotic markers in Ad-hAR HL-1 cells (P < 0.05).
      Treatment with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)
      inhibitor increased injury demonstrated by increased LDH release in ARTg, WT, and
      ARKO hearts and in Ad-hAR-expressing HL-1 cells. Cells treated with protein
      kinase C (PKC) alpha/beta inhibitor displayed significant increases in p-Akt and
      p-GSK3beta expression, and resulted in decreased LDH release. In summary, AR
      mediates changes in p-GSK3beta, in part, via PKCalpha/beta and Akt during I/R.

PMID- 22661512
TI  - Chronic infusion of angiotensin-(1-7) into the lateral ventricle of the brain
      attenuates hypertension in DOCA-salt rats.
AB  - Angiotensin-(ANG)-(1-7) is known by its central and peripheral actions, which
      mainly oppose the deleterious effects induced by accumulation of ANG II during
      pathophysiological conditions. In the present study we evaluated whether a
      chronic increase in ANG-(1-7) levels in the brain would modify the progression of
      hypertension. After DOCA-salt hypertension was induced for seven days, Sprague
      Dawley rats were subjected to 14 days of intracerebroventricular (ICV) infusion
      of ANG-(1-7) (200 ng/h, DOCA-A7) or 0.9% sterile saline. As expected, on the 21st
      day, DOCA rats presented increased mean arterial pressure (MAP) (~40%), and
      impaired baroreflex control of heart rate (HR) and baroreflex renal sympathetic
      nerve activity (RSNA) in comparison with that in normotensive control rats (CTL).
      These changes were followed by an overactivity of the cardiac sympathetic tone
      and reduction of the cardiac parasympathetic tone, and exaggerated mRNA
      expression of collagen type I (~9-fold) in the left ventricle. In contrast, DOCA
      rats treated with ANG-(1-7) ICV had an improvement of baroreflex control of HR,
      which was even higher than that in CTL, and a restoration of the baroreflex
      control of RSNA, the balance of cardiac autonomic tone, and normalized mRNA
      expression of collagen type I in the left ventricle. Furthermore, DOCA-A7 had MAP
      lowered significantly. These effects were not accompanied by significant
      circulating or cardiac changes in angiotensin levels. Taken together, our data
      show that chronic increase in ANG-(1-7) in the brain attenuates the development
      of DOCA-salt hypertension, highlighting the importance of this peptide in the
      brain for the treatment of cardiovascular diseases.

PMID- 22661513
TI  - Quantification of absolute coronary flow reserve and relative fractional flow
      reserve in a swine animal model using angiographic image data.
AB  - Coronary flow reserve (CFR) and fractional flow reserve (FFR) are important
      physiological indexes for coronary disease. The purpose of this study was to
      validate the CFR and FFR measurement techniques using only angiographic image
      data. Fifteen swine were instrumented with an ultrasound flow probe on the left
      anterior descending artery (LAD). Microspheres were gradually injected into the
      LAD to create microvascular disruption. An occluder was used to produce stenosis.
      Contrast material injections were made into the left coronary artery during image
      acquisition. Volumetric blood flow from the flow probe (Q(q)) was continuously
      recorded. Angiography-based blood flow (Q(a)) was calculated by using a time
      density curve based on the first-pass analysis technique. Flow probe-based CFR
      (CFR(q)) and angiography-based CFR (CFR(a)) were calculated as the ratio of
      hyperemic to baseline flow using Q(q) and Q(a), respectively. Relative
      angiographic FFR (relative FFR(a)) was calculated as the ratio of the normalized
      Q(a) in LAD to the left circumflex artery (LC(X)) during hyperemia. Flow probe
      based FFR (FFR(q)) was measured from the ratio of hyperemic flow with and without
      disease. CFR(a) showed a strong correlation with the gold standard CFR(q) (CFR(a)
      = 0.91 CFR(q) + 0.30; r = 0.90; P < 0.0001). Relative FFR(a) correlated linearly
      with FFR(q) (relative FFR(a) = 0.86 FFR(q) + 0.05; r = 0.90; P < 0.0001). The
      quantification of CFR and relative FFR(a) using angiographic image data was
      validated in a swine model. This angiographic technique can potentially be used
      for coronary physiological assessment during routine cardiac catheterization.

PMID- 22661515
TI  - Born to die: blood vessel regression research coming of age.

PMID- 22661514
TI  - Endothelial cell-specific FGD5 involvement in vascular pruning defines neovessel
      fate in mice.
AB  - BACKGROUND: New vessel formation contributes to organ development during
      embryogenesis and tissue repair in response to mechanical damage, inflammation,
      and ischemia in adult organisms. Early angiogenesis includes formation of an
      excessive primitive network that needs to be reorganized into a secondary
      vascular network with higher hierarchical structure. Vascular pruning, the
      removal of aberrant neovessels by apoptosis, is a vital step in this process.
      Although multiple molecular pathways for early angiogenesis have been identified,
      little is known about the genetic regulators of secondary network development.
      METHODS AND RESULTS: Using a transcriptomics approach, we identified a new
      endothelial specific gene named FYVE, RhoGEF, and PH domain-containing 5 (FGD5)
      that plays a crucial role in vascular pruning. Loss- and gain-of-function studies
      demonstrate that FGD5 inhibits neovascularization, indicated by in vitro tube
      formation, aortic-ring, and coated-bead assays and by in vivo coated-bead plug
      assays and studies in the murine retina model. FGD5 promotes apoptosis-induced
      vaso-obliteration via induction of the hey1-p53 pathway by direct binding and
      activation of cdc42. Indeed, FGD5 correlates with apoptosis in endothelial cells
      during vascular remodeling and was linked to rising p21(CIP1) levels in aging
      mice. CONCLUSION: We have identified FGD5 as a novel genetic regulator of
      vascular pruning by activation of endothelial cell-targeted apoptosis.

PMID- 22661516
TI  - Hats.

PMID- 22661517
TI  - Using principles of behavioral economics to mitigate drug shortages.

PMID- 22661518
TI  - Interleukin-18: the master regulator driving destructive and remodeling processes
      in the lungs of patients with chronic obstructive pulmonary disease?

PMID- 22661519
TI  - Chronic obstructive pulmonary disease exacerbations: accurate and easy
      measurement promises much.

PMID- 22661520
TI  - The role of the inflammasome in ventilator-induced lung injury.

PMID- 22661521
TI  - Injection drug use as a "second hit" in the pathogenesis of HIV-associated
      pulmonary hypertension.

PMID- 22661522
TI  - Update in environmental and occupational medicine 2011.

PMID- 22661523
TI  - Update in chronic obstructive pulmonary disease 2011.

PMID- 22661524
TI  - Update in pulmonary vascular diseases 2011.

PMID- 22661525
TI  - A flexible knot to untie.

PMID- 22661526
TI  - Glucocorticosteroids are potential confounders in studies of vitamin D and
      asthma.

PMID- 22661527
TI  - The Hispanic paradox and chronic obstructive pulmonary disease.

PMID- 22661528
TI  - Efficiency of continuous control of tracheal cuff pressure: electronic versus
      pneumatic devices.

PMID- 22661529
TI  - Interpreting success or failure of neurally adjusted ventilatory assist.

PMID- 22661530
TI  - Autoimmunity and chronic obstructive pulmonary disease: thinking beyond cigarette
      smoke.

PMID- 22661531
TI  - Pulmonary embolism visible on unenhanced chest computed tomography.

PMID- 22661532
TI  - Differentiated thyroid carcinoma: is there any evidence for the use of
      recombinant human TSH in thyroid hormone-secreting metastasis?

PMID- 22661534
TI  - Quantitative, simultaneous PET/MRI for intratumoral imaging with an MRI
      compatible PET scanner.
AB  - Noninvasive methods are needed to explore the heterogeneous tumor
      microenvironment and its modulation by therapy. Hybrid PET/MRI systems are being
      developed for small-animal and clinical use. The advantage of these integrated
      systems depends on their ability to provide MR images that are spatially
      coincident with simultaneously acquired PET images, allowing combined functional
      MRI and PET studies of intratissue heterogeneity. Although much effort has been
      devoted to developing this new technology, the issue of quantitative and spatial
      fidelity of PET images from hybrid PET/MRI systems to the tissues imaged has
      received little attention. Here, we evaluated the ability of a first-generation,
      small-animal MRI-compatible PET scanner to accurately depict heterogeneous
      patterns of radiotracer uptake in tumors. METHODS: Quantitative imaging
      characteristics of the MRI-compatible PET (PET/MRI) scanner were evaluated with
      phantoms using calibration coefficients derived from a mouse-sized linearity
      phantom. PET performance was compared with a commercial small-animal PET system
      and autoradiography in tumor-bearing mice. Pixel and structure-based similarity
      metrics were used to evaluate image concordance among modalities. Feasibility of
      simultaneous PET/MRI functional imaging of tumors was explored by following
      (64)Cu-labeled antibody uptake in relation to diffusion MRI using cooccurrence
      matrix analysis. RESULTS: The PET/MRI scanner showed stable and linear response.
      Activity concentration recovery values (measured and true activity concentration)
      calculated for 4-mm-diameter rods within linearity and uniform activity rod
      phantoms were near unity (0.97 +/- 0.06 and 1.03 +/- 0.03, respectively).
      Intratumoral uptake patterns for both (18)F-FDG and a (64)Cu-antibody acquired
      using the PET/MRI scanner and small-animal PET were highly correlated with
      autoradiography (r > 0.99) and with each other (r = 0.97 +/- 0.01). On the basis
      of these data, we performed a preliminary study comparing diffusion MRI and
      radiolabeled antibody uptake patterns over time and visualized movement of
      antibodies from the vascular space into the tumor mass. CONCLUSION: The MRI
      compatible PET scanner provided tumor images that were quantitatively accurate
      and spatially concordant with autoradiography and the small-animal PET
      examination. Cooccurrence matrix approaches enabled effective analysis of
      multimodal image sets. These observations confirm the ability of the current
      simultaneous PET/MRI system to provide accurate observations of intratumoral
      function and serve as a benchmark for future evaluations of hybrid
      instrumentation.

PMID- 22661535
TI  - 18F-FDG uptake to assess eosinophilic inflammation in asthma: would SUV at late
      imaging be relevant?

PMID- 22661537
TI  - Analysis of receptor tyrosine kinase ROS1-positive tumors in non-small cell lung
      cancer: identification of a FIG-ROS1 fusion.
AB  - PURPOSE: To deepen our understanding of mutant ROS1 expression, localization, and
      frequency in non-small cell lung cancer (NSCLC), we developed a highly specific
      and sensitive immunohistochemistry (IHC)-based assay that is useful for the
      detection of wild-type and mutant ROS1. EXPERIMENTAL DESIGN: We analyzed 556
      tumors with the ROS1 D4D6 rabbit monoclonal antibody IHC assay to assess ROS1
      expression levels and localization. A subset of tumors was analyzed by FISH to
      determine the percentage of these tumors harboring ROS1 translocations. Using
      specific and sensitive IHC assays, we analyzed the expression of anaplastic
      lymphoma kinase (ALK), EGFR L858R, and EGFR E746-A750del mutations in a subset of
      lung tumors, including those expressing ROS1. RESULTS: In our NSCLC cohort of
      Chinese patients, we identified 9 (1.6%) tumors expressing ROS1 and 22 (4.0%)
      tumors expressing ALK. FISH identified tumors with ALK or ROS1 rearrangements,
      and IHC alone was capable of detecting all cases with ALK and ROS1
      rearrangements. ROS1 fusion partners were determined by reverse transcriptase PCR
      identifying CD74-ROS1, SLC34A2-ROS1, and FIG-ROS1 fusions. Some of the ALK and
      ROS1 rearranged tumors may also harbor coexisting EGFR mutations. CONCLUSIONS:
      NSCLC tumors with ROS1 rearrangements are uncommon in the Chinese population and
      represent a distinct entity of carcinomas. The ROS1 IHC assay described here is a
      valuable tool for identifying patients expressing mutant ROS1 and could be
      routinely applied in clinical practice to detect lung cancers that may be
      responsive to targeted therapies.

PMID- 22661539
TI  - Diagnosing diabetes: a new paradigm.

PMID- 22661538
TI  - Genetic polymorphisms in MicroRNA-related genes as predictors of clinical
      outcomes in colorectal adenocarcinoma patients.
AB  - PURPOSE: To evaluate the effects of single-nucleotide polymorphisms (SNP) in
      microRNA-related genes on clinical outcomes in patients with colorectal cancer
      (CRC) receiving first-line fluoropyrimidine-based chemotherapy. EXPERIMENTAL
      DESIGN: Forty-one SNPs in 26 microRNA-related genes were genotyped in 1,097
      patients with CRC recruited at the University of Texas MD Anderson Cancer Center
      (Houston, TX). Patients were enrolled between 1990 and 2008 and last follow-up
      was in 2010. The associations between genotypes and recurrence-free survival
      (RFS), progression-free survival (PFS), and overall survival (OS) stratified by
      clinical stage were analyzed in 741 newly diagnosed patients (diagnosed within 1
      year) and replicated the findings in an additional 356 patients. RESULTS: In
      patients with stage III disease, mir608: rs4919510 was associated with increased
      risk for both recurrence [HR, 2.72; 95% confidence interval (CI), 1.38-5.33] and
      death (HR, 3.53; 95%CI, 1.42-8.73). The associations were confirmed in the
      replication set, and the combined HRs for training and replication sets were 1.65
      (95% CI, 1.13-2.41) for recurrence and 1.96 (95% CI, 1.19-3.21) for death,
      respectively. The mir219-1:rs213210 showed consistent association with death in
      the training set (HR, 3.86; 95% CI, 1.33-11.22), the replication set (HR, 3.33;
      95% CI, 1.39-7.98), and combined data set (HR, 3.22; 95% CI, 1.70-6.10). In
      combined analysis of these two SNPs, patients carrying the variant genotypes at
      both sites exhibited a 5.6-fold increased risk of death. CONCLUSION: Genetic
      polymorphisms in the microRNA pathway may predict prognosis in patients with
      stage III CRC treated with fluoropyrimidine-based chemotherapy.

PMID- 22661540
TI  - Cerebral vasculitis in rheumatoid arthritis.

PMID- 22661541
TI  - Chronic mild eosinophilia and severe cardiomyopathy.

PMID- 22661542
TI  - Bacterial pyomyositis in a patient with sickle cell trait and pityriasis
      amiantacea.

PMID- 22661543
TI  - Isolated colorectal mediastinal metastasis.

PMID- 22661544
TI  - A node or not a node; that is the question?

PMID- 22661545
TI  - Multimodal imaging of an atypical left atrial myxoma.

PMID- 22661546
TI  - Clinical evaluation of optical quality and intraocular scattering after posterior
      chamber phakic intraocular lens implantation.
AB  - PURPOSE: We assessed the optical quality and intraocular scattering after
      posterior chamber phakic intraocular lens implantation. METHODS: We examined
      prospectively 38 eyes of 19 consecutive patients undergoing implantable contact
      lens (ICL) implantation (mean age +/- SD 36.3 +/- 5.7 years), and 38 age-matched
      normal eyes of 19 healthy volunteers (mean age 36.4 +/- 4.9 years). We assessed
      quantitatively the values of modulation transfer function (MTF) cutoff frequency,
      Strehl ratio, objective scattering index (OSI), and the Optical Quality Analysis
      System (OQAS) values (OVs). We compared these variables in eyes undergoing ICL
      implantation to those in healthy eyes. RESULTS: The mean MTF cutoff frequency,
      Strehl ratio, OSI, OV 100%, OV 20%, and OV 9% were 28.69 +/- 8.59 cycles/degree,
      0.17 +/- 0.04, 1.06 +/- 0.48, 0.96 +/- 0.29, 0.83 +/- 0.31, and 0.83 +/- 0.32,
      respectively, 3 months after ICL implantation. We found no significant
      differences in the MTF cutoff frequency (Mann Whitney U test, P = 0.31), Strehl
      ratio (P = 0.46), OSI (P = 0.30), or OVs at contrasts of 100% (P = 0.51), 20% (P
      = 0.46), and 9% (P = 0.36), between the ICL and control groups. CONCLUSIONS: The
      optical quality parameters, such as the MTF cutoff frequency, Strehl ratio, OSI,
      or OVs in the ICL group, were not significantly different from those in the
      control group, suggesting that the optical quality and intraocular scattering of
      eyes undergoing ICL implantation essentially was equivalent to those of healthy
      eyes.

PMID- 22661547
TI  - Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage.
AB  - BACKGROUND: We previously found that a normal karyotype in a previous miscarriage
      is a predictor of subsequent miscarriage. However, the prevalence of recurrent
      miscarriage caused by an abnormal embryonic karyotype has not yet been reported,
      since embryonic karyotype is not typically analyzed during conventional
      examinations. METHODS: A total of 482 patients who underwent both embryonic
      karyotype determination and conventional examinations for recurrent miscarriage
      were enrolled in this study. The distribution of the causes and the live birth
      rate for each cause were examined. RESULTS: The total percentage of subjects in
      whom conventional causes of recurrent miscarriage could be detected was 29.5%.
      The prevalence of the abnormal embryonic karyotype was 41.1% in the subjects in
      whom no conventional causes of miscarriage could be identified. The prevalence of
      recurrent miscarriage of truly unexplained cause, that is, of subjects without
      conventional causes in whom the embryonic karyotype was ascertained to be normal,
      was 24.5%. Among the patients in whom the first determination revealed an
      abnormal embryonic karyotype, 76.2% (32/42) showed an abnormal embryonic
      karyotype in the repeat determination as well. The cumulative live birth rate
      (71.9%) in women with recurrent miscarriages caused by the abnormal embryonic
      karyotype was significantly higher than that (44.7%) in women with recurrent
      miscarriages associated with the embryonal euploidy. CONCLUSION: An abnormal
      embryonic karyotype was found to represent the commonest cause of recurrent
      miscarriage, and the percentage of cases with recurrent miscarriage of truly
      unexplained cause was limited to 24.5%.The two groups should be distinguished for
      both clinical and research purposes.

PMID- 22661548
TI  - Emerging roles of angiopoietin-like 4 in human cancer.
AB  - Angiopoietin-like 4 (ANGPTL4) is best known for its role as an adipokine involved
      in the regulation of lipid and glucose metabolism. The characterization of
      ANGPTL4 as an adipokine is largely due to our limited understanding of the
      interaction partners of ANGPTL4 and how ANGPTL4 initiates intracellular
      signaling. Recent findings have revealed a critical role for ANGPTL4 in cancer
      growth and progression, anoikis resistance, altered redox regulation,
      angiogenesis, and metastasis. Emerging evidence suggests that ANGPTL4 function
      may be drastically altered depending on the proteolytic processing and
      posttranslational modifications of ANGPTL4, which may clarify several conflicting
      roles of ANGPTL4 in different cancers. Although the N-terminal coiled-coil region
      of ANGPTL4 has been largely responsible for the endocrine regulatory role in
      lipid metabolism, insulin sensitivity, and glucose homeostasis, it has now
      emerged that the COOH-terminal fibrinogen-like domain of ANGPTL4 may be a key
      regulator in the multifaceted signaling during cancer development. New insights
      into the mechanistic action of this functional domain have opened a new chapter
      into the possible clinical application of ANGPTL4 as a promising candidate for
      clinical intervention in the fight against cancer. This review summarizes our
      current understanding of ANGPTL4 in cancer and highlights areas that warrant
      further investigation. A better understanding of the underlying cellular and
      molecular mechanisms of ANGPTL4 will reveal novel insights into other aspects of
      tumorigenesis and the potential therapeutic value of ANGPTL4.

PMID- 22661549
TI  - Chromosome microarrays in human reproduction.
AB  - BACKGROUND: Chromosome microarray (CMA) testing allows automatic and easy
      identification of large chromosomal abnormalities detectable by conventional
      cytogenetics as well as the detection of submicroscopic chromosomal imbalances.
      METHODS: A PubMed search was performed in order to review the current use of CMA
      testing in the field of human reproduction. Articles discussing the use of CMA in
      the preimplantation setting, ongoing pregnancies, miscarriages and patients with
      reproductive disorders were considered. RESULTS: A high rate of concordance
      between conventional methods of detecting chromosomal abnormalities [e.g.
      fluorescence in situ hybridization (FISH), karyotyping] and CMA was reported in
      the prenatal setting with CMA providing more comprehensive and detailed results
      as it investigates the whole genome at higher resolution. In preimplantation
      genetic screening, CMA is replacing FISH and the selection of embryos based on
      CMA has already resulted in live births. For ongoing pregnancies and
      miscarriages, CMA eliminates tissue culture failures and artifacts and allows a
      quick turnaround time. The detection of submicroscopic imbalances [or copy number
      variants (CNVs)] is beneficial when the imbalance has a clear clinical
      consequence but is challenging for previously undescribed imbalances,
      particularly for ongoing pregnancies. Recurrent CNVs have been documented in
      patients with reproductive disorders; however, the application of CMA in this
      field is still limited. CONCLUSIONS: CMA enhances reproductive medicine as it
      facilitates better understanding of the genetic aspects of human development and
      reproduction and more informed patient management. Further clinical validation of
      CMA in the prenatal setting, creation of practice guidelines and catalogs of
      newly discovered submicroscopic imbalances with clinical outcomes are areas that
      will require attention in the future.

PMID- 22661551
TI  - Adverse outcomes of Chinese medicines used for threatened miscarriage: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Threatened miscarriage is very common in early pregnancy. Chinese
      medicines have been widely used to prevent spontaneous pregnancy loss. However,
      the safety of Chinese medicines is still unknown. A systematic review was
      performed to identify and describe adverse events of Chinese medicines used for
      threatened miscarriage. METHODS: Clinical studies of Chinese medicines for
      threatened miscarriage were selected. Primary outcomes were occurrence of adverse
      effects or toxicity of Chinese medicines. Secondary outcomes were failure of
      treatment and adverse pregnancy and perinatal outcomes. RESULTS: Thirty-two
      relevant articles included 9 randomized controlled trials, 1 quasi-randomized
      controlled trial and 2 controlled trials comparing Chinese medicines alone or
      combined medicines with pharmaceuticals and 20 case series with no controls.
      Sample sizes of each study were generally small. There was variation in Chinese
      medicine formulation, dosage and duration of treatment. In the pooled randomized
      controlled trials, dry mouth, constipation and insomnia (2-10%) and intervention
      failure (3.1-22.3%), diabetic complications (3%), preterm delivery (5%) and
      neurodevelopmental morbidity (1.8%) were recorded. Meta-analysis demonstrated
      that intervention failure was significantly lower in the combined Chinese
      medicines groups than in the Western medicines controls (relative risk = 0.46;
      95% confidence interval: 0.30-0.70, I(2)= 0%). No significant differences were
      found between these groups for adverse effects and toxicity or for adverse
      pregnancy and perinatal outcomes. CONCLUSIONS: Studies varied considerably in
      design, interventions and outcome measures, therefore conclusive results remain
      elusive. In the absence of placebo-controlled trials, the safety of Chinese
      medicines for the treatment of threatened miscarriage is unknown. Rigorous
      scientific and clinical studies to assess the possible risks of Chinese medicines
      are needed.

PMID- 22661552
TI  - Evidence of the symptomatic and structural efficacy of methotrexate in daily
      practice as the first disease-modifying drug in rheumatoid arthritis despite its
      suboptimal use: results from the ESPOIR early synovitis cohort.
AB  - OBJECTIVE: To describe the use of MTX in early arthritis (EA) in daily clinical
      practice and to evaluate its 6-month symptomatic efficacy and 12-month structural
      efficacy. METHODS: Patients included in the French observational ESPOIR cohort
      were assessed. Evaluation of the symptomatic and structural efficacy was
      performed by generalized linear regression after adjustment on propensity score
      (PS) in the group of patients receiving at least 3 months of MTX vs the ones
      receiving any other treatment except LEF, SSZ or TNF inhibitors. RESULTS: Within
      the first 6 months of follow-up of 777 EA patients, 59% received a DMARD, which
      was MTX in 68% (N = 313) of patients. The mean dose of MTX was 12.7 +/- 3.8
      mg/week. Only 53.7% of the patients received folic acid supplementation. MTX was
      initiated in patients with more active and severe disease. At 6 months, in
      unadjusted analysis, patients starting MTX had a significantly higher DAS-28
      (3.58 vs 3.23; P = 0.001) and a significantly higher HAQ (0.60 vs. 0.48; P =
      0.01) compared with controls. After adjustment by PS, there were no significant
      differences. Adjustment for the PS also revealed a statistically significant
      decrease in the radiological progression at 12 months in the MTX group [total
      Sharp-van der Heijde score (SHS), 1.05 +/- 0.29 vs 2.02 +/- 0.29, P = 0.025].
      CONCLUSION: This study confirms the symptomatic and structural efficacy of MTX in
      EA in daily practice despite the non-optimal use of MTX, including low doses and
      infrequent concomitant folic acid supplementation.

PMID- 22661554
TI  - Relationship between vertebral fracture prevalence and abdominal aortic
      calcification in men.
AB  - OBJECTIVE: To study the relationship between the prevalence of vertebral
      fractures (VFs) using VF assessment (VFA) in asymptomatic men and the prevalence
      and severity of abdominal aortic calcification (AAC). METHODS: We enrolled 709
      men with mean (s.d.) age 62.4 (8.6) (range 45-89) years. Lateral VFA images and
      scans of the lumbar spine and proximal femur were obtained using a GE Healthcare
      Lunar Prodigy densitometer. VFs were defined using a combination of the Genant
      semi-quantitative (SQ) approach and morphometry. VFA images were scored for AAC
      using a validated 24-point scale. RESULTS: VFA images showed that 68 (14.2%) of
      the participants had at least one grade 2/3 VF, 82% did not have any detectable
      AAC, whereas the prevalence of significant atherosclerotic burden, defined as an
      AAC score of >=5, was 2.8%. The group of men with grade 2/3 VFs had a
      statistically significant higher AAC score and higher proportion of subjects with
      extended AAC, and lower weight, height and lumbar spine and hip BMD and T-scores
      than those without a VFA-identified VF. Multiple regression analysis showed that
      the presence of grade 2/3 VFs was significantly associated with BMI [odds ratio
      (OR 0.915; 95% CI 0.589, 0.975; P = 0.006], AAC score >=5 (OR 4.509; 95% CI
      1.505, 13.504; P = 0.007) and osteoporosis in any site (OR 5.159; 95% CI 3.116,
      8.540; P <= 0.0001). CONCLUSION: In elderly men, extended AAC is an indicator of
      the increased risk for prevalent VFs regardless of age, BMI, history of
      fractures, smoking and BMD.

PMID- 22661555
TI  - Antibodies to hnRNPs in patients with a systemic rheumatic disease with no
      antibodies to extractable nuclear antigens or dsDNA.

PMID- 22661556
TI  - A systematic review of evidence for the effectiveness of practitioner-based
      complementary and alternative therapies in the management of rheumatic diseases:
      rheumatoid arthritis.
AB  - OBJECTIVE: To critically review the evidence on the effectiveness of
      complementary therapies for patients with RA. METHODS: Randomized controlled
      trials, published in English up to May 2011, were identified using systematic
      searches of bibliographic databases and searching of reference lists. Information
      was extracted on outcomes and statistical significance in comparison with
      alternative treatments and reported side effects. The methodological quality of
      the identified studies was determined using the Jadad scoring system. All
      outcomes were considered but with a focus on patient global assessment and pain
      reporting. RESULTS: Eleven eligible trials were identified covering seven
      therapies. Three trials that compared acupuncture with sham acupuncture reported
      no significant difference in pain reduction between the groups but one out of two
      reported an improvement in patient global assessment. Except for reduction in
      physician's global assessment of treatment and disease activity reported in one
      trial, no other comparative benefit of acupuncture was seen. There were two
      studies on meditation and one each on autogenic training, healing therapy,
      progressive muscle relaxation, static magnets and tai chi. None of these trials
      reported positive comparative effects on pain but some positive effects on
      patient global assessment were noted at individual time points in the healing
      therapy and magnet therapy studies. A small number of other outcomes showed
      comparative improvement in individual trials. There were no reports of major
      adverse events. CONCLUSION: The very limited evidence available indicates that
      for none of the practitioner-based complementary therapies considered here is
      there good evidence of efficacy or effectiveness in the management of RA.

PMID- 22661557
TI  - IL-7Ralphalow memory CD8+ T cells are significantly elevated in patients with
      systemic lupus erythematosus.
AB  - OBJECTIVE: Human effector memory (EM) CD8(+) T cells include IL-7Ralpha(high) and
      IL-7Ralpha(low) cells with distinct cellular characteristics, including the
      expression of cytotoxic molecules. Both NK cells and the NK cell-associated
      molecule 2B4 that is expressed on CD8(+) T cells promote cytotoxicity. Here we
      analysed the expression of 2B4 on IL-7Ralpha(high) and IL-7Ralpha(low) EM CD8(+)
      T cells and its contribution to cytotoxicity. We also analysed the frequency of
      IL-7Ralpha(high) and IL-7Ralpha(low) EM CD8(+) T cells in patients with SLE or
      lupus and in healthy individuals given the potential role of cytotoxic CD8(+) T
      cells in the pathogenesis of lupus. METHODS: We used flow cytometry to measure
      the expression of 2B4 on IL-7Ralpha(high) and IL-7Ralpha(low) EM CD8(+) T cells
      as well as the frequency of these cell populations in the peripheral blood of
      healthy individuals and patients with SLE. Also, 2B4-mediated cytotoxicity was
      quantitated in IL-7Ralpha(high) and IL-7Ralpha(low) EM CD8(+) T cells using
      target cells with CD48 antigen. RESULTS: We found that IL-7Ralpha(high) EM CD8(+)
      T cells had higher levels of 2B4 expression compared with IL-7Ralpha(low) EM
      CD8(+) T cells. Triggering 2B4 enhanced the cytotoxic function of IL-7Ralpha(low)
      EM CD8(+) T cells against target cells. We also noticed that patients with SLE
      had an increased frequency of IL-7Ralpha(low) EM CD8(+) T cells that correlated
      with disease manifestation. CONCLUSION: Our findings show that SLE patients have
      increased IL-7Ralpha(low) EM CD8(+) T cells, possibly contributing to tissue
      damage through 2B4-mediated cytotoxicity.

PMID- 22661558
TI  - microRNA-92a expression in the sera and dermal fibroblasts increases in patients
      with scleroderma.
AB  - OBJECTIVES: microRNAs (miRNAs) play a part in various cellular activities.
      However, the role of miRNA in SSc is not fully understood. This study
      investigated the expression and role of miR-92a in SSc patients and evaluated the
      possibility that miR-92a is involved in the pathogenesis of this disease.
      METHODS: Serum samples were obtained from 61 SSc patients. mRNAs were purified
      from serum and levels of miR-92a and miR-135 were measured with quantitative real
      time PCR. miR-92a expression in dermal fibroblasts was also determined by
      quantitative real-time PCR. Immunoblotting was performed to detect MMP-1 protein.
      RESULTS: The median serum levels of miR-92a, not miR-135, were significantly
      higher in SSc patients than normal subjects. The constitutive up-regulated miR
      92a expression was also found in cultured dermal fibroblasts from SSc skin, which
      was decreased by the transfection with siRNA of TGF-beta. Furthermore, the forced
      overexpression of miR-92a in normal dermal fibroblasts using miR-92a mimic
      resulted in the down-regulation of MMP-1 expression. CONCLUSION: The increase of
      miR-92a in SSc may be due to the stimulation of intrinsic TGF-beta activation
      seen in this disease. There is also a possibility that MMP-1 is the target of miR
      92a and that increased miR-92a expression therefore plays a role in excessive
      collagen accumulation in SSc via the down-regulation of MMP-1. Clarifying the
      role of miRNAs in SSc may result in a better understanding of this disease and
      the development of new therapeutic approaches.

PMID- 22661559
TI  - Modeling nurses' acceptance of bar coded medication administration technology at
      a pediatric hospital.
AB  - OBJECTIVE: To identify predictors of nurses' acceptance of bar coded medication
      administration (BCMA). DESIGN: Cross-sectional survey of registered nurses (N=83)
      at an academic pediatric hospital that recently implemented BCMA. METHODS:
      Surveys assessed seven BCMA-related perceptions: ease of use; usefulness for the
      job; social influence from non-specific others to use BCMA; training; technical
      support; usefulness for patient care; and social influence from
      patients/families. An all possible subset regression procedure with five goodness
      of-fit indicators was used to identify which set of perceptions best predicted
      BCMA acceptance (intention to use, satisfaction). RESULTS: Nurses reported a
      moderate perceived ease of use and low perceived usefulness of BCMA. Nurses
      perceived moderate-or-higher social influence to use BCMA and had moderately
      positive perceptions of BCMA-related training and technical support. Behavioral
      intention to use BCMA was high, but satisfaction was low. Behavioral intention to
      use was best predicted by perceived ease of use, perceived social influence from
      non-specific others, and perceived usefulness for patient care (56% of variance
      explained). Satisfaction was best predicted by perceived ease of use, perceived
      usefulness for patient care, and perceived social influence from
      patients/families (76% of variance explained). DISCUSSION: Variation in and low
      scores on ease of use and usefulness are concerning, especially as these
      variables often correlate with acceptance, as found in this study. Predicting
      acceptance benefited from using a broad set of perceptions and adapting variables
      to the healthcare context. CONCLUSION: Success with BCMA and other technologies
      can benefit from assessing end-user acceptance and elucidating the factors
      promoting acceptance and use.

PMID- 22661560
TI  - From web search to healthcare utilization: privacy-sensitive studies from mobile
      data.
AB  - OBJECTIVE: We explore relationships between health information seeking activities
      and engagement with healthcare professionals via a privacy-sensitive analysis of
      geo-tagged data from mobile devices. MATERIALS AND METHODS: We analyze logs of
      mobile interaction data stripped of individually identifiable information and
      location data. The data analyzed consist of time-stamped search queries and
      distances to medical care centers. We examine search activity that precedes the
      observation of salient evidence of healthcare utilization (EHU) (ie, data
      suggesting that the searcher is using healthcare resources), in our case taken as
      queries occurring at or near medical facilities. RESULTS: We show that the time
      between symptom searches and observation of salient evidence of seeking
      healthcare utilization depends on the acuity of symptoms. We construct
      statistical models that make predictions of forthcoming EHU based on observations
      about the current search session, prior medical search activities, and prior EHU.
      The predictive accuracy of the models varies (65%-90%) depending on the features
      used and the timeframe of the analysis, which we explore via a sensitivity
      analysis. DISCUSSION: We provide a privacy-sensitive analysis that can be used to
      generate insights about the pursuit of health information and healthcare. The
      findings demonstrate how large-scale studies of mobile devices can provide
      insights on how concerns about symptomatology lead to the pursuit of professional
      care. CONCLUSION: We present new methods for the analysis of mobile logs and
      describe a study that provides evidence about how people transition from mobile
      searches on symptoms and diseases to the pursuit of healthcare in the world.

PMID- 22661561
TI  - The impact of the Spine Patient Outcome Research Trial (SPORT) results on
      orthopaedic practice.

PMID- 22661562
TI  - American College of Chest Physicians evidence-based guidelines for venous
      thromboembolic prophylaxis: the guideline wars are over.

PMID- 22661563
TI  - The spine-injured patient: initial assessment and emergency treatment.
AB  - Failure to recognize spinal column or spinal cord injuries, or improper treatment
      of them, can have catastrophic and often irreversible neurologic consequences.
      Although the initial assessment is often shared with emergency care personnel, an
      orthopaedic surgeon's perspective can elevate the priority of spinal care to the
      level that is warranted. An accurate early appraisal, including complete
      neurologic assessment, is critical. All aspects of emergent care, including
      optimal immobilization precautions, resuscitation, and choice of imaging
      modalities, should be systematically reviewed, and practice guidelines should be
      adopted by each institution. Increased vigilance is required in patients with
      underlying ankylosing spinal conditions. The use of CT in the symptomatic patient
      is established, but the use of cervical MRI in the obtunded individual is
      contentious. By informing decisions around appropriate preliminary treatment,
      particularly for persons with neurologic deficits or those at high risk for
      developing neurologic impairment, long-term outcomes can be optimized.

PMID- 22661564
TI  - Surgical management of hallux rigidus.
AB  - Hallux rigidus is the most common degenerative joint pathology of the foot.
      Untreated, it may result in notable limitations in gait, activity level, and
      daily function. Positive outcomes can be achieved with nonsurgical management;
      surgery is recommended for the sufficiently symptomatic patient for whom
      nonsurgical measures are unsuccessful. Surgery is selected based on grade of
      involvement. Early to mid-stage hallux rigidus is best managed with cheilectomy
      or cheilectomy and proximal phalanx osteotomy. Arthrodesis and arthroplasty are
      reserved for late-stage hallux rigidus.

PMID- 22661565
TI  - The musculoskeletal effects of perioperative smoking.
AB  - Although the carcinogenic consequences of smoking are well known, further
      research is needed on the effects of smoking on musculoskeletal health and
      surgical outcomes. Orthopaedic perioperative complications of smoking include
      impaired healing, increased infection, delayed and/or impaired fracture union and
      arthrodesis, and inferior arthroplasty outcomes. The incorporation of smoking
      cessation protocols such as transdermal patches, chewing gum, lozenges, inhalers,
      sprays, bupropion, and varenicline in the perioperative period may result in
      substantial benefits for patients' musculoskeletal and general health.

PMID- 22661566
TI  - Scapular dyskinesis and its relation to shoulder injury.
AB  - The scapula plays a key role in nearly every aspect of normal shoulder function.
      Scapular dyskinesis-altered scapular positioning and motion-is found in
      association with most shoulder injuries. Basic science and clinical research
      findings have led to the identification of normal three-dimensional scapular
      kinematics in scapulohumeral rhythm and to abnormal kinematics in shoulder
      injury, the development of clinical methods of evaluating the scapula (eg,
      scapular assistance test, scapular retraction test), and the formulation of
      rehabilitation guidelines. Primary scapular presentations such as scapular
      winging and snapping should be managed with a protocol that is focused on the
      scapula. Persons with associated conditions such as shoulder impingement, rotator
      cuff disease, labral injury, clavicle fracture, acromioclavicular joint injury,
      and multidirectional instability should be evaluated for scapular dyskinesis and
      treated accordingly.

PMID- 22661567
TI  - Flexor tendon sheath infections of the hand.
AB  - Flexor tendon sheath infections of the hand must be diagnosed and treated
      expeditiously to avoid poor clinical outcomes. Knowledge of the sheath's anatomy
      is essential for diagnosis and to help to guide treatment. The Kanavel cardinal
      signs are useful for differentiating conditions with similar presentations.
      Management of all but the earliest cases of pyogenic flexor tenosynovitis
      consists of intravenous antibiotics and surgical drainage of the sheath with open
      or closed irrigation. Closed irrigation may be continued postoperatively.
      Experimental data from an animal study have shown that local administration of
      antibiotics and/or corticosteroids can help lessen morbidity from the infection;
      however, additional research is required. Despite aggressive and prompt
      antibiotic therapy and surgical intervention, even otherwise healthy patients can
      expect some residual digital stiffness following flexor tendon sheath infection.
      Patients with medical comorbidities or those who present late with advanced
      infection can expect poorer outcomes, including severe digital stiffness or
      amputation.

PMID- 22661568
TI  - Implantable sensor technology: from research to clinical practice.
AB  - For decades, implantable sensors have been used in research to provide
      comprehensive understanding of the biomechanics of the human musculoskeletal
      system. These complex sensor systems have improved our understanding of the in
      vivo environment by yielding in vivo measurements of force, torque, pressure, and
      temperature. Historically, implants have been modified to be used as vehicles for
      sensors and telemetry systems. Recently, microfabrication and nanofabrication
      technology have sufficiently evolved that wireless, passive sensor systems can be
      incorporated into implants or tissue with minimal or no modification to the host
      implant. At the same time, sensor technology costs per unit have become less
      expensive, providing opportunities for use in daily clinical practice. Although
      diagnostic implantable sensors can be used clinically without significant
      increases in expense or surgical time, to date, orthopaedic smart implants have
      been used exclusively as research tools. These implantable sensors can facilitate
      personalized medicine by providing exquisitely accurate in vivo data unique to
      each patient.

PMID- 22661569
TI  - Spinal muscular atrophy: manifestations and management.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by a
      homozygous deletion in the SMN1 gene and is manifested by loss of the anterior
      horn cells of the spinal cord. Classifications of the disorder are based on age
      of onset and the patient's level of function. Scoliosis and hip subluxation or
      dislocation are two musculoskeletal manifestations associated with SMA. Severity
      of scoliosis correlates with age at presentation. Bracing has been unsuccessful
      in halting curve progression and may interfere with respiratory effort. Early
      onset scoliosis associated with SMA has been successfully treated with growing
      rod constructs, and posterior spinal fusion can be used in older children. Hip
      subluxations and dislocations are best treated nonsurgically if the patient
      reports no pain because a high rate of recurrent dislocation has been reported
      with surgical intervention.

PMID- 22661570
TI  - Modern metal-on-metal hip implants.
AB  - This Technology Overview was prepared using systematic review methodology and
      summarizes the findings of studies published as of July 15, 2011, on modern metal
      on-metal hip implants. Analyses conducted on outcomes by two joint registries
      indicate that patients who receive metal-on-metal total hip arthroplasty (THA)
      and hip resurfacing are at greater risk for revision than are patients who
      receive THA using a different bearing surface combination. Data from these
      registries also indicate that larger femoral head components have higher revision
      rates and risk of revision and that older age is associated with increased
      revision risks of large-head metal-on-metal THA. Several studies noted a
      correlation between suboptimal hip implant positioning and higher wear rates,
      local metal debris release, and consequent local tissue reactions to metal
      debris. In addition, several studies reported elevated serum metal ion
      concentrations in patients with metal-on-metal hip articulations, although the
      clinical significance of these elevated ion concentrations remains unknown.

PMID- 22661571
TI  - Switching to unboosted atazanavir reduces bilirubin and triglycerides without
      compromising treatment efficacy in UGT1A1*28 polymorphism carriers.
AB  - OBJECTIVES: Hyperbilirubinaemia is a frequent complication of atazanavir
      containing antiretroviral therapy and its severity is related to UDP-glucuronosyl
      transferase (UGT) 1A1*28 polymorphism. The aim of this study was to evaluate the
      safety and outcome of unboosted atazanavir-containing regimens based on the
      genetic constitution. METHODS: Fifty-one HIV-1-infected patients on boosted
      atazanavir were prospectively enrolled in the study. Twenty-five patients with a
      UGT1A1*28 allele switched to 400 mg of unboosted atazanavir. RESULTS: At
      baseline, UGT1A1 heterozygous and homozygous patients had significantly higher
      bilirubin levels than wild-type (P = 0.012 and P < 0.001, respectively). After
      ritonavir removal, a reduction was observed in total bilirubin (from 4.09 to 1.82
      mg/dL; P < 0.001), gamma-glutamyl transpeptidase (P = 0.015), triglycerides (P =
      0.03) and total cholesterol (P = 0.05). No significant changes in CD4 T cell
      count and no increases in viral load were observed 12 months after unboosting.
      Plasma drug monitoring after ritonavir removal revealed the presence of
      therapeutic atazanavir concentrations in all patients except one with poor
      therapy adherence. CONCLUSIONS: UGT1A1*28 is significantly related to
      hyperbilirubinaemia in HIV-1 patients receiving atazanavir. Genotyping before the
      initiation of antiretroviral therapy can reduce the emergence of severe
      hyperbilirubinaemia. Unboosted atazanavir-containing therapy is safe and
      efficacious in patients with an undetectable viral load with a UGT1A1*28
      polymorphism, allowing the use of atazanavir in patients otherwise likely unable
      to receive it.

PMID- 22661572
TI  - Liposomal encapsulation of vancomycin improves killing of methicillin-resistant
      Staphylococcus aureus in a murine infection model.
AB  - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) poses a major
      problem to public health worldwide. MRSA strains with increased resistance to
      vancomycin cause infections that are associated with greater morbidity and
      threaten the use of this once gold-standard antistaphylococcal drug. We
      investigated whether encapsulation of vancomycin within liposomes could improve
      its antistaphylococcal activity. METHODS: Two liposomal formulations of
      vancomycin were prepared using a rehydration-dehydration method. MICs and MBCs of
      the liposomal vancomycin for strains of MRSA were determined. The efficacy of one
      of the liposomal vancomycin formulations was also investigated in a time-kill
      assay in vitro and in a murine systemic infection model. RESULTS: Encapsulation
      in either liposome preparation decreased the vancomycin MICs and MBCs for MRSA
      strains by approximately 2-fold. Liposomal vancomycin increased killing of MRSA
      in vitro in a kinetic study. In a systemic murine infection model, treatment with
      a 50 mg/kg intraperitoneal injection of liposomal vancomycin improved kidney
      clearance of a USA300 strain by 1 log compared with an injection of 50 mg/kg of
      free vancomycin. CONCLUSIONS: Our findings suggest that entrapment within
      liposomes could improve the antistaphylococcal efficacy of vancomycin.

PMID- 22661573
TI  - "Skinless wonders": Body Worlds and the Victorian freak show.
AB  - In 2002, Gunther von Hagens's display of plastinated corpses opened in London.
      Although the public was fascinated by Body Worlds, the media largely castigated
      the exhibition by dismissing it as a resuscitated Victorian freak show. By using
      the freak show analogy, the British press expressed their moral objection to this
      type of bodily display. But Body Worlds and nineteenth-century displays of human
      anomalies were linked in more complex and telling ways as both attempted to be
      simultaneously entertaining and educational. This essay argues that these forms
      of corporeal exhibitionism are both examples of the dynamic relationship between
      the popular and professional cultures of the body that we often erroneously think
      of as separate and discrete. By reading Body Worlds against the Victorian freak
      show, I seek to generate a fuller understanding of the historical and enduring
      relationship between exhibitionary culture and the discourses of science, and
      thus to argue that the scientific and the spectacular have been, and clearly
      continue to be, symbiotic modes of generating bodily knowledge. 

PMID- 22661574
TI  - Requirement of upstream Hfq-binding (ARN)x elements in glmS and the Hfq C
      terminal region for GlmS upregulation by sRNAs GlmZ and GlmY.
AB  - Hfq is an important RNA-binding protein that helps bacteria adapt to stress. Its
      primary function is to promote pairing between trans-acting small non-coding RNAs
      (sRNAs) and their target mRNAs. Identification of essential Hfq-binding motifs in
      up-stream regions of rpoS and fhlA led us to ask the question whether these
      elements are a common occurrence among other Hfq-dependent mRNAs as well. Here,
      we confirm the presence of a similar (ARN)(x) motif in glmS RNA, a gene
      controlled by two sRNAs (GlmZ and GlmY) in an Hfq-dependent manner. GlmZ
      represents a canonical sRNA:mRNA pairing system, whereas GlmY is non-canonical,
      interfacing with the RNA processing protein YhbJ. We show that glmS interacts
      with both Hfq-binding surfaces in the absence of sRNAs. Even though two (ARN)(x)
      motifs are present, using a glmS:gfp fusion system, we determined that only one
      specific (ARN)(x) element is essential for regulation. Furthermore, we show that
      residues 66-72 in the C-terminal extension of Escherichia coli Hfq are essential
      for activation of GlmS expression by GlmY, but not with GlmZ. This result shows
      that the C-terminal extension of Hfq may be required for some forms of non
      canonical sRNA regulation involving ancillary components such as additional RNAs
      or proteins.

PMID- 22661575
TI  - Rational design and directed evolution of a bacterial-type glutaminyl-tRNA
      synthetase precursor.
AB  - Protein biosynthesis requires aminoacyl-transfer RNA (tRNA) synthetases to
      provide aminoacyl-tRNA substrates for the ribosome. Most bacteria and all archaea
      lack a glutaminyl-tRNA synthetase (GlnRS); instead, Gln-tRNA(Gln) is produced via
      an indirect pathway: a glutamyl-tRNA synthetase (GluRS) first attaches glutamate
      (Glu) to tRNA(Gln), and an amidotransferase converts Glu-tRNA(Gln) to Gln
      tRNA(Gln). The human pathogen Helicobacter pylori encodes two GluRS enzymes, with
      GluRS2 specifically aminoacylating Glu onto tRNA(Gln). It was proposed that
      GluRS2 is evolving into a bacterial-type GlnRS. Herein, we have combined rational
      design and directed evolution approaches to test this hypothesis. We show that,
      in contrast to wild-type (WT) GlnRS2, an engineered enzyme variant (M110) with
      seven amino acid changes is able to rescue growth of the temperature-sensitive
      Escherichia coli glnS strain UT172 at its non-permissive temperature. In vitro
      kinetic analyses reveal that WT GluRS2 selectively acylates Glu over Gln, whereas
      M110 acylates Gln 4-fold more efficiently than Glu. In addition, M110 hydrolyzes
      adenosine triphosphate 2.5-fold faster in the presence of Glu than Gln,
      suggesting that an editing activity has evolved in this variant to discriminate
      against Glu. These data imply that GluRS2 is a few steps away from evolving into
      a GlnRS and provides a paradigm for studying aminoacyl-tRNA synthetase evolution
      using directed engineering approaches.

PMID- 22661576
TI  - DR_bind: a web server for predicting DNA-binding residues from the protein
      structure based on electrostatics, evolution and geometry.
AB  - DR_bind is a web server that automatically predicts DNA-binding residues, given
      the respective protein structure based on (i) electrostatics, (ii) evolution and
      (iii) geometry. In contrast to machine-learning methods, DR_bind does not require
      a training data set or any parameters. It predicts DNA-binding residues by
      detecting a cluster of conserved, solvent-accessible residues that are
      electrostatically stabilized upon mutation to Asp(-)/Glu(-). The server requires
      as input the DNA-binding protein structure in PDB format and outputs a
      downloadable text file of the predicted DNA-binding residues, a 3D visualization
      of the predicted residues highlighted in the given protein structure, and a
      downloadable PyMol script for visualization of the results. Calibration on 83 and
      55 non-redundant DNA-bound and DNA-free protein structures yielded a DNA-binding
      residue prediction accuracy/precision of 90/47% and 88/42%, respectively. Since
      DR_bind does not require any training using protein-DNA complex structures, it
      may predict DNA-binding residues in novel structures of DNA-binding proteins
      resulting from structural genomics projects with no conservation data. The
      DR_bind server is freely available with no login requirement at
      http://dnasite.limlab.ibms.sinica.edu.tw.

PMID- 22661577
TI  - LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promotes polyadenylation
      in human mitochondria.
AB  - In human mitochondria, 10 mRNAs species are generated from a long polycistronic
      precursor that is transcribed from the heavy chain of mitochondrial DNA, in
      theory yielding equal copy numbers of mRNA molecules. However, the steady-state
      levels of these mRNAs differ substantially. Through absolute quantification of
      mRNAs in HeLa cells, we show that the copy numbers of all mitochondrial mRNA
      species range from 6000 to 51,000 molecules per cell, indicating that
      mitochondria actively regulate mRNA metabolism. In addition, the copy numbers of
      mitochondrial mRNAs correlated with their cellular half-life. Previously, mRNAs
      with longer half-lives were shown to be stabilized by the LRPPRC/SLIRP complex,
      which we find that cotranscriptionally binds to coding sequences of mRNAs. We
      observed that the LRPPRC/SLIRP complex suppressed 3' exonucleolytic mRNA
      degradation mediated by PNPase and SUV3. Moreover, LRPPRC promoted the
      polyadenylation of mRNAs mediated by mitochondrial poly(A) polymerase (MTPAP) in
      vitro. These findings provide a framework for understanding the molecular
      mechanism of mRNA metabolism in human mitochondria.

PMID- 22661578
TI  - NASSAM: a server to search for and annotate tertiary interactions and motifs in
      three-dimensional structures of complex RNA molecules.
AB  - Similarities in the 3D patterns of RNA base interactions or arrangements can
      provide insights into their functions and roles in stabilization of the RNA 3D
      structure. Nucleic Acids Search for Substructures and Motifs (NASSAM) is a graph
      theoretical program that can search for 3D patterns of base arrangements by
      representing the bases as pseudo-atoms. The geometric relationship of the pseudo
      atoms to each other as a pattern can be represented as a labeled graph where the
      pseudo-atoms are the graph's nodes while the edges are the inter-pseudo-atomic
      distances. The input files for NASSAM are PDB formatted 3D coordinates. This web
      server can be used to identify matches of base arrangement patterns in a query
      structure to annotated patterns that have been reported in the literature or that
      have possible functional and structural stabilization implications. The NASSAM
      program is freely accessible without any login requirement at
      http://mfrlab.org/grafss/nassam/.

PMID- 22661579
TI  - FastML: a web server for probabilistic reconstruction of ancestral sequences.
AB  - Ancestral sequence reconstruction is essential to a variety of evolutionary
      studies. Here, we present the FastML web server, a user-friendly tool for the
      reconstruction of ancestral sequences. FastML implements various novel features
      that differentiate it from existing tools: (i) FastML uses an indel-coding
      method, in which each gap, possibly spanning multiples sites, is coded as binary
      data. FastML then reconstructs ancestral indel states assuming a continuous time
      Markov process. FastML provides the most likely ancestral sequences, integrating
      both indels and characters; (ii) FastML accounts for uncertainty in ancestral
      states: it provides not only the posterior probabilities for each character and
      indel at each sequence position, but also a sample of ancestral sequences from
      this posterior distribution, and a list of the k-most likely ancestral sequences;
      (iii) FastML implements a large array of evolutionary models, which makes it
      generic and applicable for nucleotide, protein and codon sequences; and (iv) a
      graphical representation of the results is provided, including, for example, a
      graphical logo of the inferred ancestral sequences. The utility of FastML is
      demonstrated by reconstructing ancestral sequences of the Env protein from
      various HIV-1 subtypes. FastML is freely available for all academic users and is
      available online at http://fastml.tau.ac.il/.

PMID- 22661580
TI  - ExPASy: SIB bioinformatics resource portal.
AB  - ExPASy (http://www.expasy.org) has worldwide reputation as one of the main
      bioinformatics resources for proteomics. It has now evolved, becoming an
      extensible and integrative portal accessing many scientific resources, databases
      and software tools in different areas of life sciences. Scientists can henceforth
      access seamlessly a wide range of resources in many different domains, such as
      proteomics, genomics, phylogeny/evolution, systems biology, population genetics,
      transcriptomics, etc. The individual resources (databases, web-based and
      downloadable software tools) are hosted in a 'decentralized' way by different
      groups of the SIB Swiss Institute of Bioinformatics and partner institutions.
      Specifically, a single web portal provides a common entry point to a wide range
      of resources developed and operated by different SIB groups and external
      institutions. The portal features a search function across 'selected' resources.
      Additionally, the availability and usage of resources are monitored. The portal
      is aimed for both expert users and people who are not familiar with a specific
      domain in life sciences. The new web interface provides, in particular, visual
      guidance for newcomers to ExPASy.

PMID- 22661581
TI  - ConoDictor: a tool for prediction of conopeptide superfamilies.
AB  - ConoDictor is a tool that enables fast and accurate classification of
      conopeptides into superfamilies based on their amino acid sequence. ConoDictor
      combines predictions from two complementary approaches-profile hidden Markov
      models and generalized profiles. Results appear in a browser as tables that can
      be downloaded in various formats. This application is particularly valuable in
      view of the exponentially increasing number of conopeptides that are being
      identified. ConoDictor was written in Perl using the common gateway interface
      module with a php submission page. Sequence matching is performed with hmmsearch
      from HMMER 3 and ps_scan.pl from the pftools 2.3 package. ConoDictor is freely
      accessible at http://conco.ebc.ee.

PMID- 22661582
TI  - Probing hybridization parameters from microarray experiments: nearest-neighbor
      model and beyond.
AB  - In this article, it is shown how optimized and dedicated microarray experiments
      can be used to study the thermodynamics of DNA hybridization for a large number
      of different conformations in a highly parallel fashion. In particular, free
      energy penalties for mismatches are obtained in two independent ways and are
      shown to be correlated with values from melting experiments in solution reported
      in the literature. The additivity principle, which is at the basis of the nearest
      neighbor model, and according to which the penalty for two isolated mismatches is
      equal to the sum of the independent penalties, is thoroughly tested. Additivity
      is shown to break down for a mismatch distance below 5 nt. The behavior of
      mismatches in the vicinity of the helix edges, and the behavior of tandem
      mismatches are also investigated. Finally, some thermodynamic outlying sequences
      are observed and highlighted. These sequences contain combinations of GA
      mismatches. The analysis of the microarray data reported in this article provides
      new insights on the DNA hybridization parameters and can help to increase the
      accuracy of hybridization-based technologies.

PMID- 22661584
TI  - A large-scale association study for nanoparticle C60 uncovers mechanisms of
      nanotoxicity disrupting the native conformations of DNA/RNA.
AB  - Nano-scale particles have attracted a lot of attention for its potential use in
      medical studies, in particular for the diagnostic and therapeutic purposes.
      However, the toxicity and other side effects caused by the undesired interaction
      between nanoparticles and DNA/RNA are not clear. To address this problem, a model
      to evaluate the general rules governing how nanoparticles interact with DNA/RNA
      is demanded. Here by, use of an examination of 2254 native nucleotides with
      molecular dynamics simulation and thermodynamic analysis, we demonstrate how the
      DNA/RNA native structures are disrupted by the fullerene (C60) in a physiological
      condition. The nanoparticle was found to bind with the minor grooves of double
      stranded DNA and trigger unwinding and disrupting of the DNA helix, which
      indicates C60 can potentially inhibit the DNA replication and induce potential
      side effects. In contrast to that of DNA, C60 only binds to the major grooves of
      RNA helix, which stabilizes the RNA structure or transforms the configuration
      from stretch to curl. This finding sheds new light on how C60 inhibits reverse
      transcription as HIV replicates. In addition, the binding of C60 stabilizes the
      structures of RNA riboswitch, indicating that C60 might regulate the gene
      expression. The binding energies of C60 with different genomic fragments varies
      in the range of -56 to -10 kcal mol(-1), which further verifies the role of
      nanoparticle in DNA/RNA damage. Our findings reveal a general mode by which C60
      causes DNA/RNA damage or other toxic effects at a systematic level, suggesting it
      should be cautious to handle these nanomaterials in various medical applications.

PMID- 22661583
TI  - Mitochondrial DNA deletions are associated with non-B DNA conformations.
AB  - Mitochondrial DNA (mtDNA) deletions are a primary cause of mitochondrial disease
      and are believed to contribute to the aging process and to various
      neurodegenerative diseases. Despite strong observational and experimental
      evidence, the molecular basis of the deletion process remains obscure. In this
      study, we test the hypothesis that the primary cause of mtDNA vulnerability to
      breakage resides in the formation of non-B DNA conformations, namely hairpin,
      cruciform and cloverleaf-like elements. Using the largest database of human mtDNA
      deletions built thus far (753 different cases), we show that site-specific
      breakage hotspots exist in the mtDNA. Furthermore, we discover that the most
      frequent deletion breakpoints occur within or near predicted structures, a result
      that is supported by data from transgenic mice with mitochondrial disease. There
      is also a significant association between the folding energy of an mtDNA region
      and the number of breakpoints that it harbours. In particular, two clusters of
      hairpins (near the D-loop 3'-terminus and the L-strand origin of replication) are
      hotspots for mtDNA breakage. Consistent with our hypothesis, the highest number
      of 5'- and 3'-breakpoints per base is found in the highly structured tRNA genes.
      Overall, the data presented in this study suggest that non-B DNA conformations
      are a key element of the mtDNA deletion process.

PMID- 22661585
TI  - Initial treatment patterns over time for anaplastic oligodendroglial tumors.
AB  - Anaplastic oligodendroglial tumors are rare neoplasms with no standard approach
      to treatment. We sought to determine patterns of treatment delivered over time
      and identify clinical correlates of specific strategies using an international
      retrospective cohort of 1013 patients diagnosed from 1981-2007. Prior to 1990,
      most patients received radiotherapy (RT) alone as initial postoperative
      treatment. After 1990, approximately 50% of patients received both RT and
      chemotherapy (CT) sequentially and/or concurrently. Treatment with RT alone
      became significantly less common (67% in 1980-1984 vs 5% in 2005-2007, P <
      .0001). CT alone was more frequently administered in later years (0% in 1980-1984
      vs 38% in 2005-2007; P < .0001), especially in patients with 1p19q codeleted
      tumors (57% of codeleted vs 4% with no deletion in 2005-2007; P < .0001).
      Temozolomide replaced the combination of procarbazine, lomustine, and vincristine
      (PCV) among patients who received CT alone or with RT (87% vs 2% in 2005-2007).
      In the most recent time period, patients with 1p19q codeleted tumors were
      significantly more likely to receive CT alone (with temozolomide), whereas RT
      with temozolomide was a significantly more common treatment strategy than either
      CT or RT alone in cases with no deletion (P < .0001). In a multivariate
      polytomous logistic regression model, the following were significantly associated
      with type of treatment delivered: date (5-year interval) of diagnosis (P <
      .0001), 1p19q codeletion (P < .0001), pure anaplastic oligodendroglioma histology
      (P < .01), and frontal lobe predominance (P < .05). Limited level 1 evidence is
      currently available to guide treatment decisions, and ongoing phase III trials
      will be critical to understanding the optimal therapy.

PMID- 22661587
TI  - Complete longitudinal analyses of the randomized, placebo-controlled, phase III
      trial of sunitinib in patients with gastrointestinal stromal tumor following
      imatinib failure.
AB  - PURPOSE: To analyze final long-term survival and clinical outcomes from the
      randomized phase III study of sunitinib in gastrointestinal stromal tumor
      patients after imatinib failure; to assess correlative angiogenesis biomarkers
      with patient outcomes. EXPERIMENTAL DESIGN: Blinded sunitinib or placebo was
      given daily on a 4-week-on/2-week-off treatment schedule. Placebo-assigned
      patients could cross over to sunitinib at disease progression/study unblinding.
      Overall survival (OS) was analyzed using conventional statistical methods and the
      rank-preserving structural failure time (RPSFT) method to explore cross-over
      impact. Circulating levels of angiogenesis biomarkers were analyzed. RESULTS: In
      total, 243 patients were randomized to receive sunitinib and 118 to placebo, 103
      of whom crossed over to open-label sunitinib. Conventional statistical analysis
      showed that OS converged in the sunitinib and placebo arms (median 72.7 vs. 64.9
      weeks; HR, 0.876; P = 0.306) as expected, given the cross-over design. RPSFT
      analysis estimated median OS for placebo of 39.0 weeks (HR, 0.505, 95% CI, 0.262
      1.134; P = 0.306). No new safety concerns emerged with extended sunitinib
      treatment. No consistent associations were found between the pharmacodynamics of
      angiogenesis-related plasma proteins during sunitinib treatment and clinical
      outcome. CONCLUSIONS: The cross-over design provided evidence of sunitinib
      clinical benefit based on prolonged time to tumor progression during the double
      blind phase of this trial. As expected, following cross-over, there was no
      statistical difference in OS. RPSFT analysis modeled the absence of cross-over,
      estimating a substantial sunitinib OS benefit relative to placebo. Long-term
      sunitinib treatment was tolerated without new adverse events.

PMID- 22661588
TI  - Antioxidant enzyme polymorphisms and neuropsychological outcomes in
      medulloblastoma survivors: a report from the Childhood Cancer Survivor Study.
AB  - Psychological or neurocognitive impairment is often seen in medulloblastoma
      survivors after craniospinal radiation; however, significant variability in
      outcomes exists. This study investigated the role of antioxidant enzyme
      polymorphisms in moderating this outcome and hypothesized that patients who had
      polymorphisms associated with lower antioxidant enzyme function would have a
      higher occurrence of impairment. From the Childhood Cancer Survivor Study (CCSS)
      cohort, 109 medulloblastoma survivors and 143 siblings were identified who
      completed the CCSS Neurocognitive Questionnaire (NCQ) and the Brief Symptom
      Inventory-18 (BSI-18) and who provided buccal DNA samples. Real-time polymerase
      chain reaction (PCR) allelic discrimination was used for SOD2 (rs4880), GPX1
      (rs1050450), and GSTP1 (rs1695 and rs1138272) genotyping and PCR for GSTM1 and
      GSTT1 gene deletions. Outcomes on NCQ and BSI-18 subscale scores were examined in
      association with genotypes and clinical factors, including age at diagnosis, sex,
      and radiation dose, using univariate and multivariate analysis of variance.
      Patients <7 years of age at diagnosis displayed more problems with task
      efficiency (P < .001) and fewer problems with somatic complaints (P = .004) than
      did patients >=7 years of age. Female patients reported more organization
      problems than did male patients (P = .02). Patients with homozygous GSTM1 gene
      deletion reported higher anxiety (mean null genotype = 47.3 +/- 9.2, non-null =
      43.9 +/- 7.8; P = .04), more depression (null = 51.0 +/- 9.8, non-null = 47.0 +/-
      9.4; P = .03), and more global distress (null = 50.2 +/- 9.7, non-null = 45.2 +/-
      9.9; P = .01). All associations for the GSTM1 polymorphism remained statistically
      significant in a multivariate model controlling for age, sex, and radiation dose.
      Homozygous GSTM1 gene deletion was consistently associated with greater
      psychological distress in medulloblastoma survivors across multiple domains,
      suggesting that this genotype may predispose patients for increased emotional
      late effects.

PMID- 22661589
TI  - Combined surgical and endovascular treatment of complex cerebrovascular diseases
      in the hybrid operating room.
AB  - BACKGROUND: Although most neurovascular diseases can be treated either by
      microsurgical or endovascular means, a subset of patients may require a combined
      approach. Patient transfer from the operating room (OR) to the angiosuite has
      been a fundamental drawback of this type of approach. OBJECTIVE: The purpose of
      this study is to report our clinical experience performing combined surgical and
      endovascular procedures for neurovascular diseases in the hybrid OR. METHODS: 29
      patients with neurovascular diseases underwent combined endovascular and surgical
      procedures in a single session: 16 were scheduled combined treatment and 13 were
      emergency combined procedures. Of the emergency cases, three were rescue
      surgeries after endovascular complications. Three patients had ruptured
      intracranial aneurysms, eight had unruptured intracranial aneurysms, eight had
      arteriovenous malformations and eight had arteriovenous fistulae; two patients
      had either a spinal tumor or dural arteriovenous fistulae. RESULTS: All combined
      procedures were performed in a single session without changing the patient's
      surgical position. In cases of ruptured arteriovenous malformations or aneurysms
      with hematoma, an emergency embolization was performed to assist the surgical
      procedure. Combined superficial temporal artery-middle cerebral artery (STA-MCA)
      bypass followed by endovascular parent artery trapping were successfully
      performed for complex large or giant aneurysms. There were two periprocedural
      ischemic complications. Of the three patients who underwent surgical rescue after
      endovascular complications, two remained intact and one died despite immediate
      surgical procedures. CONCLUSION: A combined endovascular and surgical approach
      conducted in a hybrid OR provides a new strategy for the treatment of complex
      neurovascular diseases.

PMID- 22661591
TI  - On how mammary gland reprogramming metalloproteinases couple form with function.

PMID- 22661593
TI  - FDA approves 18F-florbetapir PET agent.

PMID- 22661594
TI  - Lower doses of 131I?

PMID- 22661595
TI  - Diagnostic radiology and nuclear radiology program requirements changes
      challenged.

PMID- 22661590
TI  - Wnt signaling in mammary glands: plastic cell fates and combinatorial signaling.
AB  - The mouse mammary gland is an outstanding developmental model that exemplifies
      the activities of many of the effector pathways known to organize mammalian
      morphogenesis; furthermore, there are well-characterized methods for the specific
      genetic manipulation of various mammary epithelial cell components. Among these
      signaling pathways, Wnt signaling has been shown to generate plasticity of fate
      determination, expanding the genetic programs available to cells in the mammary
      lineage. It is responsible first for the appearance of the mammary fate in
      embryonic ectoderm and then for maintaining bi-potential basal stem cells in
      adult mammary ductal trees. Recent technical developments have led to the
      separate analysis of various mammary epithelial cell subpopulations, spurring the
      investigation of Wnt-dependent interactions. Although Wnt signaling was shown to
      be oncogenic for mouse mammary epithelium even before being identified as the
      principle oncogenic driver for gut epithelium, conclusive data implicating this
      pathway as a tumor driver for breast cancer lag behind, and we examine potential
      reasons.

PMID- 22661597
TI  - Rosalyn S. Yalow: a personal and scientific memoir.

PMID- 22661598
TI  - SNM leadership update: a president's year in review.

PMID- 22661599
TI  - Flow failure from intracranial atherosclerotic disease: a rationale for
      endovascular intervention in a population with recurrent symptoms despite maximal
      medical therapy.
AB  - The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in
      Intracranial Stenosis (SAMMPRIS) trial, the first randomized trial to compare
      best medical therapies with angioplasty and stenting, was halted prematurely
      owing to a 30-day stroke rate of 14.7% in the angioplasty and stenting arm
      compared with 5.8% in the medical management arm. These results have led to a
      paradigm shift away from interventional therapies and back to dual antiplatelet
      therapy and aggressive medical therapies only for these patients. However, there
      appears to be a subset of patients with intracranial atherosclerotic disease
      (ICAD) who are different from the general SAMMPRIS cohort and are defined by flow
      failure from severe intracranial arterial stenosis resulting in recurrent
      ischemic symptoms despite maximal medical therapy. Offering the option of
      endovascular revascularization seems appropriate in this patient population,
      given their recurrent ischemic events regardless of aggressive medical therapies.
      This paper provides a rationale for reconsidering the role of interventional
      therapies in patients with critical intracranial stenosis and presents four
      patients with flow failure from ICAD and persistent symptoms of ischemia,
      regardless of dual antiplatelet and adjuvant medical therapies, who subsequently
      improved with angioplasty. Consideration of alternative patient populations and
      treatment paradigms seems to carry particular relevance now as the endovascular
      treatment of intracranial atheromatous disease is currently receiving intense
      scrutiny by those medical specialties involved in the care of stroke patients, as
      well as the public at large.

PMID- 22661600
TI  - Novel aneurysm neck reconstruction device: initial experience in an experimental
      preclinical bifurcation aneurysm model.
AB  - INTRODUCTION: Treatment of wide-necked bifurcation aneurysms often poses
      procedural and long-term outcome challenges. The initial preclinical experience
      with the Pulsar Vascular Aneurysm Neck Reconstruction Device (PVANRD) in a canine
      bifurcation model is described. METHODS: Experimental bifurcation vein pouch
      aneurysms were surgically created in the carotid arteries of eight dogs.
      Endovascular coiling of the aneurysms with assistance of the PVANRD was performed
      in all cases with acute performance compared with Y-stenting. RESULTS: Twelve
      devices were deployed in the eight cases. Deployment of the devices was
      straightforward and successfully protected the parent artery and maintained
      patency of the bifurcation in all cases, despite the use of oversized coils.
      CONCLUSION: The PVANRD is a novel bifurcation stent that facilitates treatment of
      wide-necked bifurcation aneurysms compared with currently available adjunctive
      devices.

PMID- 22661601
TI  - Characteristic MR and CT imaging findings of hepatobiliary paragonimiasis and
      their pathologic correlations.
AB  - BACKGROUND: Hepatobiliary paragonimiasis (HP) is not commonly encountered and may
      be confused with hepatobiliary tumors; however, computed tomography (CT) and
      magnetic resonance imaging (MRI) features of HP allow this entity to be
      distinguished from other diseases. PURPOSE: To present the CT and MRI findings in
      patients with HP and to describe some specific imaging findings along with their
      pathological correlations. MATERIAL AND METHODS: Imaging and clinical findings of
      21 patients (9 boys/men and 12 girls/women; age range 3-67 years; mean age 40
      years) who were diagnosed with HP were retrospectively evaluated. Among these
      patients, 16 underwent CT examination only, two had MR examination only, and
      three underwent both CT and MR. All patients underwent surgery, and the HP
      diagnosis was confirmed by the surgical and histopathologic results. RESULTS:
      Chronic abdominal pain or back pain was reported by 14 patients, severe abdominal
      pain with acute onset was reported by one patient, and six patients were
      asymptomatic and were discovered incidentally. Peripheral eosinophilia was
      present in 14 patients (14/21, 66.7%), and abnormal liver function tests were
      found in 16 patients (16/21, 76.2%). Of the 19 patients who underwent CT imaging,
      17 patients showed multiple mixed hypodense lesions or multiple cysts with
      inlaying septation with separate irregular rims or circular enhancement on post
      contrast CT images. Tunnel-shaped microabscesses and necrotic cavities were found
      in the lesions of 12 of those 17 patients. The other two patients showed smaller
      cystic masses. MRI showed faveolate T1 hypointense and T2 hyperintense areas in
      the liver parenchyma with rim or peripheral enhancement. Nodular or circular
      hyperintense materials were found scattered in the lesions on T1-weighted
      imaging. CONCLUSION: CT and MRI can reveal the radiological-pathological features
      of HP. Together with laboratory findings, MRI and CT findings may provide
      diagnostic clues, especially in endemic areas, that are very important for the
      selection of treatment methods.

PMID- 22661602
TI  - Bedside diagnosis of pleural effusion with a latest generation hand-carried
      ultrasound device in intensive care patients.
AB  - BACKGROUND: Further development established hand-carried ultrasound (HCU) imagers
      in daily clinical workflow providing several advantages such as fast bedside
      availability and prompt diagnosis. PURPOSE: To evaluate the diagnostic yield of a
      latest generation HCU imager compared to chest radiography (CR) for the detection
      of pleural effusion (PE) in intensive care patients. MATERIAL AND METHODS: Forty
      eight hemithoraces of 24 patients on surgical intensive care units were enrolled
      in this study. All hemithoraces were evaluated using both HCU and CR. Definite
      diagnosis of PE was achieved using a high-end ultrasound system as standard of
      reference. Statistical analysis was performed using 2 * 2 tables and a McNemar
      test. A P value of <0.05 was considered statistically significant. RESULTS: PE
      was present in 35 of 48 hemithoraces (73%). The HCU examination was carried out
      technically successfully in all hemithoraces. Sensitivity and specificity of HCU
      for the diagnosis of PE was 91% and 100%, respectively, whereas sensitivity and
      specificity of CR was 74% and 31%, respectively. The difference between HCU and
      CR was statistically significant with respect to specificity but not sensitivity
      (P = 0.008 and P = 0.11, respectively). CONCLUSION: Due to its ease of use and
      its high diagnostic yield HCU systems of the latest generation constitute a
      helpful technique for the primary assessment of PE.

PMID- 22661603
TI  - Prognostic value of tumor burden measurement using the number of tumors in non
      surgical patients with non-small cell lung cancer.
AB  - BACKGROUND: No study to test the feasibility and prognostic value of the number
      of primary tumors, the number of positive lymph nodes, and the total number of
      tumors in the whole body as tumor burden measurements on FDG PET/CT imaging has
      been reported. PURPOSE: To determine whether the number of tumors seen in 18F-FDG
      PET scans can be a prognostic factor in non-surgical patients with non-small cell
      lung cancer (NSCLC). MATERIAL AND METHODS: One hundred and forty patients with
      histologically proven NSCLC and baseline 18F-FDG PET scan before therapy were
      identified in this retrospective analysis. The total number of tumors (TTn) in
      the whole body, the number of primary tumors (Tn), positive lymph nodes (Nn), and
      distant metastases (Mn), along with the maximum standardized uptake values
      (SUV(max)) of the tumors were measured. Inter-observer variability of the total
      number of tumors, counted by two radiologists, was assessed. Survival analyses
      were performed to determine the prognostic value of the number of tumors.
      RESULTS: Concordance correlation coefficients for the TTn, Tn, Nn, and Mn were
      all greater than 0.85. TTn and Nn were strong prognostic factors of NSCLC
      patients' overall survival (OS). In univariate Cox regression models, gender,
      stage, TTn, Nn, and Mn were statistically significant factors (P = 0.016, 0.032,
      <0.001, <0.001, and 0.006, respectively). In multivariate Cox regression models,
      TTn and Nn remained as statistically significant predictors for survival with
      hazard ratios (HR) of 1.06 (P = 0.001) and 1.11 (P = 0.002), respectively, after
      adjusting for clinical stage based 7th edition of TNM staging system, age,
      gender, and SUV(max). Patients with a TTn <=4 (cutpoint based on median value)
      had a median OS of 15.2 months compared with 9.0 months for those with TTn >4.
      CONCLUSION: Measuring the number of tumors on FDG PET imaging is easy to perform
      with minimal inter-observer variability. The total number of tumors and number of
      nodal metastases, as metabolic tumor burden measurements in 18F-FDG PET/CT, are
      prognostic markers independent of clinical stage, age, gender, and SUV
      measurement in non-surgical patients with NSCLC.

PMID- 22661604
TI  - The compensation experience of hand-arm vibration syndrome in British Columbia.
AB  - BACKGROUND: Hand-arm vibration syndrome (HAVS) is a relatively common
      occupational disease, especially in certain industrial sectors. Affected workers
      in many jurisdictions are eligible for compensation, but little is known about
      the behaviour and characteristics of workers seeking compensation for HAVS. AIMS:
      To characterize the workers seeking compensation for HAVS based on demographics,
      occupation and disease characteristics. METHODS: All accepted claims for HAVS
      from 1999 to 2008 in British Columbia were reviewed. RESULTS: The average
      claimant was 50 years old and had worked 25 years. The average latency period for
      developing HAVS symptoms was 18 years, and half the number of symptomatic workers
      waited 5 years or more before filing a claim. Loggers developed symptoms, on
      average, after 17 years of exposure, significantly earlier than mechanics, who
      developed symptoms after 24 years of work. Loggers waited longer than mechanics
      to file claims, with a median delay of 6 years, compared with 3 years for
      mechanics. The majority of HAVS claims involved severer vascular and
      sensorineural symptoms. CONCLUSIONS: Claimants commonly delay filing compensation
      claims and this may result in severer symptoms when the claims are filed. Further
      study is required to explain this delay.

PMID- 22661605
TI  - Risks of cataract in Nigerian metal arc welders.
AB  - BACKGROUND: Occupational exposure to ultraviolet (UV) radiation from welding is
      considered a risk factor for cataract and other eye disorders, but the evidence
      for such effects is limited. AIMS: To identify any increased risk of developing
      cataract from metal arc welding and to investigate the associated risk factors.
      METHODS: A cross-sectional study was carried out on male welders and control
      subjects (not engaged in welding) from five fabrication and construction
      companies in Port Harcourt, Nigeria. A questionnaire was used to gather
      information regarding their demography and lifestyle, along with their
      occupational, medical and ocular histories. Cataract was identified by external
      examination and ophthalmoscopy. RESULTS: A total of 117 welders and 105 controls
      participated. There was no statistically significant increase in the risk of
      cataract in welders after adjusting for age, smoking status, family history of
      cataract, outdoor work and history of eye injury. There was a strong association
      between work-related eye-injury history and cataract. Only 60% of welders were
      wearing eye protection when the eye injury occurred. The majority of the eye
      injuries (72%) occurred during welding and grinding operations. CONCLUSIONS: The
      findings of this study suggest that the main occupational risk factor for
      cataract was a history of eye injuries. The role of UV (or optical) radiation
      appeared to be less important than impact eye injuries associated with welding
      allied processes. It is therefore important that welders are provided with
      different types of eye protection and are informed about which type should be
      used, and when, so that they can be protected against optical and impact
      injuries.

PMID- 22661606
TI  - Occupational rhinitis caused by concurrent sensitization to two different
      allergens.
AB  - BACKGROUND: Exposure to wheat flour and guar gum is a well-known cause of
      occupational respiratory allergies among workers in the food processing industry.
      To date, there have been no reports of occupational rhinitis (OR) caused
      concurrently by two different allergens present in the workplace. AIMS: To report
      a case of OR likely to be induced concurrently by exposure to wheat flour and
      guar gum in a mid-40s male employed in the food processing industry. METHODS:
      Allergy tests and nasal challenge tests were performed to investigate and confirm
      the diagnosis of OR. We discuss potential mechanisms involved in the observed
      dual sensitization. RESULTS: The patient showed positive responses to wheat and
      guar gum extracts on skin prick testing. The total IgE was 1680 kU/l (0-100
      kU/l). The diagnosis of OR was confirmed by nasal challenge tests with wheat
      flour and guar gum on different days. In contrast to the control day, the
      challenge with flour and guar gum induced an immediate clinical reaction
      associated with a decrease in nasal volume measured by acoustic rhinometry. The
      patient was advised to avoid exposure to wheat and guar gum, which resulted in a
      gradual resolution of nasal symptoms. CONCLUSIONS: Co-sensitization and cross
      reactivity are possible mechanisms involved in cases of concurrent sensitization
      to related and unrelated allergens in patients complaining of work-related
      rhinitis symptoms.

PMID- 22661608
TI  - Visual working memory for amplitude-modulated shapes.
AB  - We investigated the trade-off between capacity and precision in visual working
      memory with two different tasks: delayed discrimination and recall. The stimuli
      were radial frequency patterns that require global pooling of local visual
      features. The thresholds in delayed amplitude discrimination were measured with a
      two-interval, forced-choice setup using the Quest procedure. In the recall
      experiment, the observers' task was to adjust the amplitude of a probe to match
      the amplitude of a cued item. For one item, the amplitude thresholds were low
      (0.01-0.05) and the adjustments precise (standard deviations, 0.03-0.05). As the
      number of items increased from one to six, there was a linear, 6-to-14-fold
      increase in the thresholds (0.14-0.29) and a 1.5-to-3-fold increase in the
      standard deviations (0.06-0.11). No sudden or complete breakdown in performance
      was observed for any subject. The results show a continuous trade-off between
      memory capacity and precision; six items can be discriminated with the same
      performance level (75% correct) as one item if the difference between the stimuli
      is set accordingly. Thus, the stimulus discriminability determines the capacity
      of visual working memory, and the trade-off between the capacity and precision is
      linear.

PMID- 22661609
TI  - Local flicker stimulation evokes local retinal blood velocity changes.
AB  - We investigated the effect of localized visual stimulation on human retinal blood
      velocity using an adaptive optics scanning laser ophthalmoscope (AOSLO). To
      measure the blood velocity response, the AOSLO scanning raster was moved over the
      target arteries and red blood cell velocity was measured. Localized visual
      stimuli were delivered by projecting flicker patterns inside or outside the
      target artery's downstream region. The blood velocity increased in the presence
      of a flicker stimulus in the downstream region but not when outside the
      downstream region. The blood velocity increased more with larger area of
      stimulation. This increase was significant even when the stimulus was smaller
      than 600 MUm * 600 MUm. These findings suggest that when the retina regulates its
      blood flow to metabolic demands, it regulates blood velocity in the vascular
      system selectively, according to activity of neurons within its field of
      influence.

PMID- 22661610
TI  - Using detection or identification paradigms when assessing visual development: is
      a shift in paradigm necessary?
AB  - Given the inherent difference in judgment required to complete visual detection
      and identification tasks, it is unknown whether task selection differentially
      affects visual performance as a function of development. The aim of the present
      study is therefore to systematically assess and contrast visual performance using
      these two types of paradigms in order to determine whether paradigm-contingent
      differences in performance exist across different periods of development. To do
      so, we assessed sensitivity to both luminance- and texture-defined stationary and
      dynamic gratings using both detection and identification paradigms. Results
      demonstrated a relatively unchanged pattern of performance from the school ages
      through adolescence, suggesting that sensitivity was not differentially affected
      by choice of paradigm as a function of development. However, when averaged across
      age groups, a paradigm-contingent difference in sensitivity was evidenced for
      dynamic, texture-defined gratings only; it was easier to detect the spatial
      location of the gratings compared with identifying the direction of their motion.
      Paradigm-contingent differences were not evidenced for luminance-defined stimuli
      (whether stationary or dynamic), or for stationary, texture-defined gratings. In
      general, visual performance measured using either detection or identification
      paradigms is comparable across ages, particularly when information is stationary
      and defined by more simple visual attributes, such as luminance. Therefore, the
      use of detection paradigms might be advantageous under most circumstances when
      assessing visual abilities of very young and/or clinical populations in order to
      minimize potential challenges not related to visual perception (i.e.,
      attentional) in these populations. Finally, paradigm-contingent differences in
      performance specific to dynamic, texture-defined information will be discussed.

PMID- 22661611
TI  - Saccadic inhibition is accompanied by large and complex amplitude modulations
      when induced by visual backward masking.
AB  - Saccadic inhibition refers to the strong temporary decrease in saccadic
      initiation observed when a visual distractor appears shortly after the onset of a
      saccadic target. Here, to gain a better understanding of this phenomenon, we
      assessed whether saccade amplitude changes could accompany these modulations of
      latency distributions. As previous studies on the saccadic system using visual
      backward masking--a protocol in which the mask appears shortly after the target-
      showed latency increases and amplitude changes, we suspected that this could be a
      condition in which amplitude changes would accompany saccadic inhibition. We show
      here that visual backward masking produces a strong saccadic inhibition. In
      addition, this saccadic inhibition was accompanied by large and complex amplitude
      changes: a first phase of gain decrease occurred before the saccadic inhibition;
      when saccades reappeared after the inhibition, they were accurate before rapidly
      entering into a second phase of gain decrease. We observed changes in saccade
      kinematics that were consistent with the possibility of saccades being
      interrupted during these two phases of gain decrease. These results show that the
      onset of a large stimulus shortly after a first one induces the previously
      reported saccadic inhibition, but also induces a complex pattern of amplitude
      changes resulting from a dual amplitude perturbation mechanism with fast and slow
      components.

PMID- 22661612
TI  - Contemporary management of infrarenal aortic graft infection: early and late
      results in 82 patients.
AB  - Management of aortic graft infection (AGI) remains contentious. The purpose of
      this study was to evaluate factors of clinical significance which influence the
      outcome of different treatment modalities for AGI. From 2000 to 2008, 82
      consecutive patients were treated for AGI. In situ reconstruction (ISR) was
      performed in 63 patients with various conduits, extra-anatomic reconstruction
      (EAR) in 11, conservative treatment in five and resection without reconstruction
      in three. The perioperative mortality rate for the series (33%) was similar for
      EAR and ISR and was higher in patients with secondary aortoenteric fistula (P <
      0.001) in those undergoing emergency aortic reconstruction (P < 0.001) and in AGI
      caused by virulent organisms (P < 0.05). Fifteen (27%) of the surviving patients
      developed a recurrence of infection (RI). EAR patients were more exposed to RI (P
      < 0.04). In conclusion, ISR may be more appropriate for AGI, but this study
      cannot draw a conclusion relating to the optimal conduit for ISR.

PMID- 22661613
TI  - Influence of aneurysm wall stiffness and the presence of intraluminal thrombus on
      the wall movement of an aneurysm - an in vitro study.
AB  - The purpose of this in vitro study was to investigate the influence of aneurysm
      wall stiffness and of the presence of intraluminal thrombus (ILT) on aneurysm
      wall movement. Three latex aneurysms were used with different wall stiffness. The
      aneurysms, equipped with 20 tantalum markers, were attached to an in vitro
      circulation model. Fluoroscopic roentgenographic stereo photogrammetric analysis
      was used to measure marker movement during six cardiac cycles at three different
      systemic pressures. To investigate the influence of ILT on wall movement, we
      repeated the same experiment with one of the aneurysms. The aneurysm sac was then
      filled with one of two E-moduli differing thrombus analogues (Novalyse 8 and 20)
      or with perfusate as a control. It was noted that the amplitude of the wall
      movement (mm) increased significantly (P < 0.05) as the compliance of the wall
      increased. The mean amplitude of the wall movement decreased (P < 0.05) as the
      stiffness (E-modulus) of the ILT increased. In conclusion, ILT has a 'cushioning
      effect'. Wall movement (and theoretically wall stress) diminishes when the
      stiffness of the ILT increases. Compliance of the aneurysm wall influences wall
      movement. When the stiffness of the wall increases, the wall movement diminishes.

PMID- 22661614
TI  - Modernizing the treatment of venous thoracic outlet syndrome.
AB  - This study aims to quantify the management and outcomes of patients treated for
      venous thoracic outlet syndrome (vTOS) over a seven-year period. A retrospective
      case-note review of all patients undergoing first rib resection at a regional
      vascular unit between January 1, 2002 and December 31, 2009 was performed.
      Treatment pathways and outcomes recorded as freedom from symptoms and venous
      patency were analyzed. Thirty-five patients were identified with vTOS. Ninety-one
      percent of patients had patent veins at discharge from clinical follow-up and
      were symptom-free at a median of 44 months. Patients treated within seven days of
      symptoms (94.7 versus 85.7, P = 0.060), with catheter-directed thrombolysis (94
      versus 87.5% P = 0.702) and excision of first rib in less than 30 days (100
      versus 85.7%, P = 0.002), had improved symptom-free rates. In conclusion, early
      referral, immediate catheter-directed thrombolysis, perioperative balloon
      venoplasty and early thoracic outlet decompression may provide a suitable model
      for improving outcomes in vTOS.

PMID- 22661615
TI  - Duplex ultrasound interpretation criteria for inferior mesenteric arteries.
AB  - There is no specific duplex ultrasound (DUS) criteria for the diagnosis of
      inferior mesenteric artery (IMA) stenosis. This study will define the optimal
      duplex velocity values with the best overall accuracy (OA) in detecting >=50%
      stenosis of the IMAs. Eighty-five IMAs with both DUS and mesenteric arteriography
      were analyzed. Eighty-five IMAs were examined: 45 were normal, 12 with <50%
      stenosis, eight with >=50-69% stenosis and 15 with >=70% stenosis (including
      occlusion) based on angiography. The mean peak systolic velocities (PSVs) for a
      normal IMA, <50% and >=50% stenosis was 105, 215 and 392 cm/second, respectively
      (P < 0.0001). The most accurate PSV in detecting >=50% stenosis was >=250
      cm/second with a sensitivity of 90%, a specificity of 96% and an OA of 95%. The
      most accurate end-diastolic velocity (EDV) in detecting >=50% stenosis was >=80%
      or >=90 cm/second, with an OA of 86%, a sensitivity of 60% and a specificity of
      100%. The most accurate ratio in detecting >=50% stenosis was >=4 or >=4.5 with
      an OA of 93%.Receiver operator curves analysis showed that the PSV was not better
      than EDV and PSV ratio in detecting >=50% stenosis (P = 0.1661 and 0.4568,
      respectively). In conclusion, specific IMA PSVs, EDVs and IMA/aortic systolic
      ratios can be used in detecting significant IMA stenosis with reasonable
      accuracy.

PMID- 22661616
TI  - Family and youth factors associated with health beliefs and health outcomes in
      youth with type 1 diabetes.
AB  - OBJECTIVE: To examine the association of family organization with metabolic
      control in adolescents with type 1 diabetes through the mechanisms of family self
      efficacy for diabetes and disease management. METHOD: Data from the baseline
      assessment of a longitudinal RCT were used, wherein 257 adolescent-parent dyads
      (adolescents aged 11-14) each completed the family organization subscale of the
      Family Environment Scale, the self-efficacy for Diabetes Self-Management Scale,
      the Diabetes Behavior Rating Scale, and 2 24-hr diabetes interviews. RESULTS:
      Structural equation modeling showed greater family organization was associated
      indirectly with better disease management behaviors via greater family self
      efficacy (beta = .38, p < .001). Greater self-efficacy was indirectly associated
      with better metabolic control via better disease management both concurrently
      (beta = -.37, p < .001) and prospectively (beta = -.26, p < .001). The full model
      indicates more family organization is indirectly associated with better metabolic
      control concurrently and prospectively through greater self-efficacy and better
      disease management (beta = -.13, p < .001). CONCLUSIONS: Understanding the
      mechanisms by which family organization is associated with metabolic control
      provides insight into possible avenues of prevention/intervention for better
      diabetes management.

PMID- 22661617
TI  - Commentary: pediatric psychology research informing policy for AIDS-affected
      youth in Africa.

PMID- 22661618
TI  - Influences of spontaneous perspective taking on spatial and identity processing
      of faces.
AB  - Previous research suggests that people, when interacting with another agent, are
      sensitive to the other's visual perspective on the scene. The present study
      investigated how spontaneously another's different spatial perspective is taken
      into account and how this affects the processing of jointly attended stimuli.
      Participants viewed upright or inverted faces alone, next to another person (same
      spatial perspective), or opposite another person (different spatial perspectives)
      while electroencephalography (EEG) was recorded. The task (counting male faces)
      was in no way related to spatial aspects of the stimuli, and thus did not
      encourage perspective taking. EEG results revealed no general differences between
      viewing faces alone or with another person. However, when holding different
      perspectives (sitting opposite each other), the amplitudes of the N170 and of the
      N250 significantly increased for upright faces. This indicates that people
      spontaneously represented the other's different perspective, which led to higher
      demands for structural encoding (N170) and to increased allocation of attention
      to face recognition (N250) for stimuli that are typically processed configurally.
      When holding different spatial perspectives, thus, people may not merely
      represent that the other sees the object or scene differently, but how the
      object/scene looks for the other. 

PMID- 22661619
TI  - Is race erased? Decoding race from patterns of neural activity when skin color is
      not diagnostic of group boundaries.
AB  - Several theories suggest that people do not represent race when it does not
      signify group boundaries. However, race is often associated with visually salient
      differences in skin tone and facial features. In this study, we investigated
      whether race could be decoded from distributed patterns of neural activity in the
      fusiform gyri and early visual cortex when visual features that often covary with
      race were orthogonal to group membership. To this end, we used multivariate
      pattern analysis to examine an fMRI dataset that was collected while participants
      assigned to mixed-race groups categorized own-race and other-race faces as
      belonging to their newly assigned group. Whereas conventional univariate analyses
      provided no evidence of race-based responses in the fusiform gyri or early visual
      cortex, multivariate pattern analysis suggested that race was represented within
      these regions. Moreover, race was represented in the fusiform gyri to a greater
      extent than early visual cortex, suggesting that the fusiform gyri results do not
      merely reflect low-level perceptual information (e.g. color, contrast) from early
      visual cortex. These findings indicate that patterns of activation within
      specific regions of the visual cortex may represent race even when overall
      activation in these regions is not driven by racial information. 

PMID- 22661620
TI  - Fish fats and the heart.

PMID- 22661621
TI  - A meta-analysis of omega-3 fatty acids and incidence of atrial fibrillation.
AB  - OBJECTIVES: Atrial fibrillation (AF) is associated with higher health care costs.
      Although omega-3 (n-3) fatty acids have been associated with a decreased risk of
      coronary heart disease, their effects on the risk of AF are inconsistent. We
      therefore sought to review the relation between n-3 fatty acids and the risk of
      AF. METHODS: Using an extensive online search, we conducted a meta-analysis of
      new onset incident/recurrent AF following exposure to fish/fish oil or long-chain
      n-3 polyunsaturated fatty acids. A random-effect model was used and between
      studies heterogeneity was estimated with I(2). The quality of studies was
      assessed using Jadad and United States Preventive Services Task Force (USPSTF)
      scoring systems. All analyses were performed with RevMan (version 5.0.20).
      RESULTS: Seven cohort studies and 11 randomized controlled trials (RCTs) were
      included in this meta-analysis. The pooled odds ratio (OR) was 0.79 (95%
      confidence interval [CI] = 0.56-1.12; p = 0.19) for RCTs and 0.83 (95% CI = 0.59
      1.16; p = 0.27) for cohort studies. On sensitivity analysis, no statistically
      significant difference was noted when stratified by study design or quality of
      the studies (as graded by Jadad or USPSTF scoring systems). CONCLUSION: This
      study does not suggest a major effect of fish/fish oil or n-3 fatty acids on the
      risk of AF.

PMID- 22661622
TI  - Probiotics in the treatment of the liver diseases.
AB  - The concept that interactions between the gut, the liver, and the immune system
      play an important role in liver diseases is an old concept that has recently seen
      a resurgence in interest. Altered intestinal bacterial flora and gut-associated
      endotoxemia are increasingly recognized as critical components in both
      nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD).
      Probiotics have been proposed in the treatment and prevention of many conditions,
      including the liver diseases. Probiotics are live microorganisms that, when
      consumed in adequate amounts, confer a health benefit to the host. There are many
      mechanisms by which probiotics enhance intestinal health and influence the gut
      liver axis, including modulation of the intestinal microflora, modification of
      intestinal barrier function, and immunomodulation. The present review summarizes
      the recent studies highlighting the role of the intestinal microflora in the
      development of NAFLD and ALD and the potential efficacy of probiotics as a
      therapeutic strategy for liver diseases.

PMID- 22661623
TI  - Body mass, vitamin D and alcohol intake, lactose intolerance, and television
      watching influence bone mineral density of young, healthy Canadian women.
AB  - OBJECTIVE: To report bone mineral density (BMD) in young, reportedly healthy
      Canadian women and to determine whether lifestyle factors that have been
      associated with bone health in older women are also associated with BMD in young
      women. METHOD: We recruited a convenience sample of 52 female undergraduate
      students in the Applied Human Nutrition program at the University of Guelph,
      Ontario, Canada. BMD was measured at the femoral neck, lumbar spine (L1 to L4),
      and whole body using a Discovery Wi (Hologic Inc.) dual-energy x-ray
      absorptiometer. Subjects completed a questionnaire to collect demographics,
      medical history, physical activity levels, and dietary habits; in addition, a
      subset of subjects (n = 31) completed a food frequency questionnaire to collect
      data on calcium and vitamin D intake. BMD data were examined using T- and Z-score
      classifications established by the World Health Organization (WHO); multiple
      regression analysis was used to predict BMD with biological and lifestyle
      variables. RESULTS: Mean BMD measured at the femoral neck, lumbar spine, and
      whole body was 0.863 +/- 0.11, 1.019 +/- 0.09, and 1.085 +/- 0.07 g/cm(2),
      respectively. Body mass and body mass index were significantly positively
      correlated with BMD at all 3 sites. Television watching, lactose intolerance,
      number of alcoholic drinks consumed per week, and age were used to develop a
      linear regression model to predict whole-body BMD (r(2) = 0.727, p < 0.001).
      CONCLUSIONS: Based on criteria established by the WHO, women in this group
      presented with lower than expected BMD.

PMID- 22661624
TI  - Statin therapy depresses fat metabolism in older individuals.
AB  - OBJECTIVE: Statins (3-hydroxy-3-methylglutaryl coenzyme A [HMG CoA] reductase
      inhibitors) reduce blood lipoproteins and reduce the risk of cardiovascular
      events. However, they may reduce fat metabolism. This study tested the hypothesis
      that total body fat oxidation is reduced by statins in older subjects and the
      reduction is not due to substrate availability. METHODS: A total of 14 elderly
      patients (71 +/- 6 years) on statin therapy were compared with 14 matched elderly
      controls (75 +/- 7 years). Subjects were tested for respiratory exchange ratio
      (RER) during both maximal and submaximal sustained (70% Vo(2max)) exercise to
      voluntary exhaustion. Blood samples were drawn for lipoprotein analysis and
      substrate availability. RESULTS: RER was significantly higher in subjects taking
      statins during both the max and submax tests, indicating reduced fat oxidation.
      Blood lipoprotein levels after a fast were not different between the statin and
      control groups. Levels of glucose, lactate, or triglyceride were not different
      between groups; however, free fatty acid levels were elevated by exercise in the
      statin group. Fat oxidation was significantly reduced in older subjects taking
      statin drugs that were not associated with diet, exercise, and fitness, which
      were matched between groups, nor availability of fat from the blood, which was
      higher in the statin group. CONCLUSION: Although statin therapy normalizes blood
      lipoproteins, it reduced fat metabolism in older individuals, which cannot be a
      result of lower availability from blood.

PMID- 22661625
TI  - Low birth weight as cardiometabolic risk in Japanese high school girls.
AB  - OBJECTIVE: To examine the relationships between birth weight and metabolic
      syndrome (MS) risk factors in healthy Japanese high school girls. METHODS: After
      obtaining informed consent, we carried out health surveys for the Food
      Educational Program (FEP) in 2007 and 2008 in 243 healthy Japanese high school
      girls aged 16.4 +/- 1.4 years and examined anthropometric measurements, including
      abdominal circumference, systolic and diastolic blood pressures (SBP and DBP,
      respectively), triglycerides (TG), high-density lipoprotein cholesterol (HDL),
      insulin, and blood glucose to calculate insulin resistance after fasting for 3
      hours after lunch. Birth weight was checked by maternity record book, and food
      customs were recorded using a questionnaire. We analyzed the prevalence of MS
      risk factors by Bonferroni test following 1-way analysis of variance and their
      relationships with birth weight by correlation analyses. RESULTS: According to
      criteria for MS risk factors in Japanese children and adults, the prevalence of
      obesity, high blood pressure, dyslipidemia, and high blood glucose was 7.4%,
      9.1%, 7.0%, and 16.0%, respectively, and MS was detected in only 1 girl who had
      obesity and 2 more risks (high SBP and TG). Among 180 subjects who reported their
      birth weights, birth weights were significantly inversely related with SBP (p =
      0.007), DBP (p = 0.033), TG (p = 0.009), insulin level (p = 0.047), insulin
      resistance ( p= 0.050), and number of metabolic risk factors (p = 0.022).
      Thirteen girls (7.2%) whose birth weights were lower than 2500 g had
      significantly higher SBP (p = 0.037), DBP (p = 0.032), TG (p = 0.011), insulin
      level (p=0.037), and insulin resistance (p = 0.043), than 31 girls (17.2%) with
      birth weights equal to or more than 3400 g. CONCLUSION: The association of low
      birth weight could be detected to be significant with such risks of MS as SBP,
      DBP, TG, insulin level, and insulin resistance even in healthy Japanese high
      school girls, indicating the importance of follow-up and FEP for children with
      low birth weight for the prevention of MS in the later life.

PMID- 22661626
TI  - Iron status and self-perceived health, well-being, and fatigue in female
      university students living in New Zealand.
AB  - OBJECTIVE: To determine the relationship between iron depletion and self
      perceived health, well-being, and fatigue in a female university student
      population living in New Zealand. METHODS: A total of 233 women aged 18-44 years
      studying at Massey University, Auckland, were included in this cross-sectional
      analysis. Serum ferritin (SF), hemoglobin (Hb), and C-reactive protein (CRP) were
      analyzed from a venipuncture blood sample. Participants completed the SF-36v2
      General Health Survey (SF-36) and the Multidimensional Fatigue Symptom Inventory
      Short Form (MFSI-SF) questionnaire, and anthropometric measurements (height and
      weight) and data on demographics, lifestyle, and medical history were obtained.
      Characteristics of iron-sufficient (SF >= 20 MUg/L, Hb >= 120 g/L) and iron
      depleted (SF < 20 MUg/L, Hb >= 120 g/L) participants were compared, and multiple
      regression analyses were carried out to determine predictors of health, well
      being, and fatigue using a p value of <0.01 to indicate statistical significance
      because multiple comparisons were being made. RESULTS: There were no significant
      differences in self-perceived health and well-being determined using the SF-36
      questionnaire between women who were iron sufficient and women who were iron
      depleted. Although MFSI-SF physical fatigue was significantly lower in those with
      iron depletion (p = 0.008), it was not predicted by current iron status in a
      multivariate model controlling for factors expected to be associated with iron
      status and fatigue (p = 0.037). However, smoking, a history of suboptimal iron
      status, and having a current medical condition were significant (negative)
      predictors of MFSI-SF physical fatigue, explaining 22.5% of the variance (p <
      0.001). There were no significant differences in the other measures of fatigue
      determined using the MFSI-SF between women who were iron sufficient and those who
      were iron depleted. CONCLUSIONS: Women with iron depletion did not differ
      significantly from women who were iron sufficient with regard to self-perceived
      health, well-being, or fatigue. Future studies investigating fatigue should
      control for previous diagnosis of suboptimal iron status, smoking, and presence
      of a medical condition.

PMID- 22661627
TI  - Metabolic risk factors and arterial stiffness in Indian children of parents with
      metabolic syndrome.
AB  - OBJECTIVE: To investigate the possible association between metabolic syndrome
      (MS) and arterial stiffness in Indian children with parental MS status. METHODS:
      A cross-sectional study was conducted in 140 overweight/obese and 60 normal
      weight Indian children (mean age, 11.4 +/- 2.8 years) along with one of their
      parents during 2008-2009. Data on weight, height, blood pressure, serum lipids,
      zinc, insulin, and glucose were collected. Intima media thickness (CIMT) and
      stiffness parameters were assessed in the right carotid artery. Physical activity
      and diet were assessed using structured questionnaires. Body composition was
      measured using dual-energy x-ray absorptiometry. RESULTS: A gradual increase in
      the percentage of MS children with an increasing number of MS components in
      parents was observed. Mean values for arterial stiffness, pulse wave velocity,
      and elastic modulus were significantly higher in MS children of MS parents than
      in MS children of normal parents (p < 0.05). A significant correlation was
      observed for lifestyle, metabolic, and arterial parameters among child-parent
      pairs (p < 0.05). Multiple logistic regression revealed that children's CIMT and
      arterial stiffness were significantly associated (p < 0.01) with their serum
      levels of triglycerides, high-density lipoprotein, and zinc, as well as with
      parental MS-CIMT. CONCLUSION: Parental MS status and lifestyle factors increase
      the risk of MS and arterial abnormalities in children.

PMID- 22661628
TI  - Effectiveness of four manual breast pumps for mothers after preterm delivery in a
      developing country.
AB  - BACKGROUND: Hospital-grade electric pumps may be useful to initiate and sustain
      adequate milk production for mothers who are unable to breast-feed their babies
      hospitalized at special care nurseries (SCN), but their cost is generally not
      affordable for SCN and for most mothers in developing countries. Therefore,
      manual breast pumps (MBPs) can be an alternative, but the best option is unknown
      considering clinical parameters and mothers' preference from among currently
      available MBPs. OBJECTIVE: To compare the effectiveness of four MBPs in terms of
      milk volume, nutritional composition, and breast emptying in order to assist in
      making a choice for health care personnel and mothers in SCN settings. Duration
      of expression and maternal preference were also evaluated as secondary outcomes.
      METHODS: Mothers of preterm infants used 4 MBPs in a random order, 2 with a
      squeeze-handle mechanism (Isis and Harmony) and 2 with a cylindrical mechanism
      (Little Heart and Evenflo), both at the hospital and in home settings using each
      pump over one 24-hour period. RESULTS: Milk volume, nutritional composition,
      breast emptying, and duration of expression were not different among MBPs. Scale
      of maternal preference rated higher those with the squeeze-handle mechanism than
      the cylindrical mechanism (p < 0.05). CONCLUSIONS: There was no difference found
      in the effectiveness across the four pumps tested. The mothers' rating for
      comfort and ease of use showed a marked difference between pumps. These factors,
      plus cost, need to be considered when evaluating manual pumps for use in SCN
      settings in developing countries.

PMID- 22661629
TI  - Bioenergetic effects of mitochondrial-targeted coenzyme Q analogs in endothelial
      cells.
AB  - Mitochondrial-targeted analogs of coenzyme Q (CoQ) are under development to
      reduce oxidative damage induced by a variety of disease states. However, there is
      a need to understand the bioenergetic effects of these agents and whether or not
      these effects are related to redox properties, including their known pro-oxidant
      effects. We examined the bioenergetic effects of two mitochondrial-targeted CoQ
      analogs in their quinol forms, mitoquinol (MitoQ) and plastoquinonyl-decyl
      triphenylphosphonium (SkQ1), in bovine aortic endothelial cells. We used an
      extracellular oxygen and proton flux analyzer to assess mitochondrial action at
      the intact-cell level. Both agents, in dose-dependent fashion, reduced the oxygen
      consumption rate (OCR) directed at ATP turnover (OCR(ATP)) (IC50 values of 189 +/
      13 nM for MitoQ and 181 +/- 7 for SKQ1; difference not significant) while not
      affecting or mildly increasing basal oxygen consumption. Both compounds increased
      extracellular acidification in the basal state consistent with enhanced
      glycolysis. Both compounds enhanced mitochondrial superoxide production assessed
      by using mitochondrial-targeted dihydroethidium, and both increased H2O2
      production from mitochondria of cells treated before isolation of the organelles.
      The manganese superoxide dismutase mimetic manganese(III) tetrakis(1-methyl-4
      pyridyl)porphyrin did not alter or actually enhanced the actions of the targeted
      CoQ analogs to reduce OCR(ATP). In contrast, N-acetylcysteine mitigated this
      effect of MitoQ and SkQ1. In summary, our data demonstrate the important
      bioenergetic effects of targeted CoQ analogs. Moreover, these effects are
      mediated, at least in part, through superoxide production but depend on
      conversion to H2O2. These bioenergetic and redox actions need to be considered as
      these compounds are developed for therapeutic purposes.

PMID- 22661630
TI  - Quantification of Hepatic UDP glucuronosyltransferase 1A splice variant
      expression and correlation of UDP glucuronosyltransferase 1A1 variant expression
      with glucuronidation activity.
AB  - The UDP glucuronosyltransferase (UGT) 1A gene cluster encodes nine UGT1A family
      members via splicing of individual first exons to common exons 2 through 5. Each
      of these nine UGT1As can also undergo alternative splicing at their 3' ends by
      using an alternate exon 5, resulting in 27 different UGT1A mRNA species with each
      UGT1A gene encoding three different combinations of 5A and 5B UGT1A exons. To
      examine the importance of UGT1A exon 5 splice variants on overall UGT1A activity,
      a nested quantitative polymerase chain reaction assay was developed to accurately
      assess the combined expression of exon 5 splice variants (termed v2/v3) versus
      the expression of wild-type (termed v1) for each specific UGT1A. v1 expression
      was 16-, 17-, 57- and 29-fold higher than that observed for the levels of v2/v3
      for UGTs 1A1, 1A4, 1A6, and 1A9, respectively, in normal human liver specimens.
      In a series of 58 normal human liver specimens, the expression of both UGT1A1 v1
      and v2/v3 mRNAs was positively correlated with raloxifene glucuronidation
      activity in corresponding microsomes prepared from the same specimens (p <
      0.0001, r2 = 0.720; p = 0.0002, r2 = 0.241, respectively), with expression of
      both variants lower in individuals homozygous for the UGT1A1*28 allele (42% for
      v1, p = 0.041; 53% for v2/v3, p = 0.0075). The expression of UGT1A1 v2/v3 was 1.6
      fold higher than v1 (p = 0.03) in HepG2 cells, and short interfering RNA
      knockdown of HepG2 v2/v3 increased raloxifene glucuronidation activity by 83%.
      Together, these data suggest that hepatic UGT1A v2/v3 mRNA species are minor form
      variants in human livers from most individuals.

PMID- 22661631
TI  - Screening tests for Chlamydia trachomatis or Neisseria gonorrhoeae using the
      cobas 4800 PCR system do not require a second test to confirm: an audit of
      patients issued with equivocal results at a sexual health clinic in the Northwest
      of England, U.K.
AB  - OBJECTIVES: To assess the clinical utility of supplementary PCRs following a
      positive cobas 4800 CT/NG PCR screening test result. METHODS: Laboratory reports,
      for Chlamydia trachomatis or Neisseria gonorrhoeae, issued to genitourinary
      medicine patients between April 2010 and April 2011 were reviewed
      retrospectively. Positive reports were routinely confirmed by supplementary PCRs
      and N gonorrhoeae culture. Clinical records of patients with unconfirmed positive
      (equivocal) reports were retrieved to determine if the infection was confirmed by
      a second sample obtained at patient recall and the impact of this process on
      antibiotic management. RESULTS: Over 15 000 patients were tested during the study
      period. The prevalence of chlamydia and gonorrhoea was 972 (5.75%) and 76
      (0.50%), respectively. A further 78 chlamydia and 2 gonorrhoea equivocal reports
      were issued. Only 56 (72%) patients with an equivocal chlamydia report returned
      to the clinic, and of these, only 41 (73%) gave a second sample to retest.
      Positive predictive value (PPV) of the PCR screening test was calculated at 98.0%
      and 97.5% for detection of chlamydia infection from urine and rectal swabs,
      respectively. Most patients accepted antibiotic treatment before their infection
      status had been confirmed. Prevalence of gonorrhoea infection was low but the PPV
      of the screening PCR in urine specimens remained high (98.75%). CONCLUSIONS:
      Equivocal reports introduce delays to patient management, while the risk of
      unnecessary antibiotic therapy appears acceptable to most patients. The cobas
      4800 CT/NG PCR screening assay can achieve UK testing standards (PPV >90%) for
      chlamydia, and low prevalence gonorrhoea in urine without supplementary tests. A
      patient-led confirmation algorithm is proposed.

PMID- 22661632
TI  - Assessing user preferences for sexually transmitted infection testing services: a
      discrete choice experiment.
AB  - OBJECTIVE: To assess user preferences for different aspects of sexually
      transmitted infection (STI) testing services. DESIGN: A discrete choice
      experiment. SETTING: 14 centres offering tests for STIs in East Sussex, England.
      PARTICIPANTS: People testing for STIs. MAIN OUTCOME MEASURE: (Adjusted) ORs in
      relation to preferred service characteristics. RESULTS: 3358 questionnaires were
      returned; mean age 26 (SD 9.4) years. 70% (2366) were recruited from
      genitourinary medicine (GUM) clinics. The analysis suggested that the most
      important characteristics to users were whether 'staff had specialist STI
      knowledge' compared with 'staff without it' (OR 2.55; 95% CI 2.47 to 2.63) and
      whether 'tests for all STIs' were offered rather than 'some' (OR 2.19; 95% CI
      2.12 to 2.25). They remained the most important two service characteristics
      despite stratifying the analysis by variables such as age and sex. Staff levels
      of expertise were viewed as particularly important by people attending CASH
      centres, women and non-men who have sex with men. A 'text or call to a mobile
      phone' and 'dropping in and waiting' were generally the preferred methods of
      results reporting and appointment system, respectively. CONCLUSIONS: This study
      suggests that people testing for STIs place particular importance on testing for
      all infections rather than some and staff with specialist STI knowledge. Thus,
      targets based purely on waiting up to 48 h for an appointment are misguided from
      a user perspective.

PMID- 22661633
TI  - Detection rates of Mycoplasma genitalium and Chlamydia trachomatis infections in
      Novosibirsk, Siberia, in 2010-2011.

PMID- 22661636
TI  - Hedgehog signaling.

PMID- 22661634
TI  - T-cell tolerance: central and peripheral.
AB  - Somatic recombination of TCR genes in immature thymocytes results in some cells
      with useful TCR specificities, but also many with useless or potentially self
      reactive specificities. Thus thymic selection mechanisms operate to shape the T
      cell repertoire. Thymocytes that have a TCR with low affinity for self-peptide
      MHC complexes are positively selected to further differentiate and function in
      adaptive immunity, whereas useless ones die by neglect. Clonal deletion and
      clonal diversion (Treg differentiation) are the major processes in the thymus
      that eliminate or control self-reactive T cells. Although these processes are
      thought to be efficient, they fail to control self-reactivity in all
      circumstances. Thus, peripheral tolerance processes exist wherein self-reactive T
      cells become functionally unresponsive (anergy) or are deleted after encountering
      self-antigens outside of the thymus. Recent advances in mechanistic studies of
      central and peripheral T-cell tolerance are promoting the development of
      therapeutic strategies to treat autoimmune disease and cancer and improve
      transplantation outcome.

PMID- 22661637
TI  - On oncogenes and tumor suppressor genes in the mammary gland.

PMID- 22661635
TI  - Regulation and function of autophagy during cell survival and cell death.
AB  - Autophagy is an important catabolic process that delivers cytoplasmic material to
      the lysosome for degradation. Autophagy promotes cell survival by elimination of
      damaged organelles and proteins aggregates, as well as by facilitating
      bioenergetic homeostasis. Although autophagy has been considered a cell survival
      mechanism, recent studies have shown that autophagy can promote cell death. The
      core mechanisms that control autophagy are conserved between yeast and humans,
      but animals also possess genes that regulate autophagy that are not present in
      yeast. These regulatory differences may be explained by the need to control
      autophagy in a cell context-specific manner in multicellular animals, such as
      during cell survival and cell death. Autophagy was thought to be a bulk
      cytoplasmic degradation mechanism, but recent studies have shown that specific
      cargo is recruited for degradation. This suggests the possibility that either
      cell survival or death may be regulated by selective autophagic clearance of
      cytoplasmic material. Here we summarize the mechanisms that regulate autophagy
      and how they may contribute to cell survival and death.

PMID- 22661638
TI  - On molecular mechanisms guiding embryonic mammary gland development.

PMID- 22661639
TI  - Sex in sports medicine.

PMID- 22661642
TI  - Influence of gender in the psychoneuroimmunological response to therapeutic
      interval exercise.
AB  - Interval exercise has been used as an alternative modality to continuous exercise
      in patients with various conditions. Although interval exercise can improve
      health status, it may also exert deleterious effects. Few data are available on
      differences in psychoneuroimmunological response to high-intensity interval
      exercise, and it is not known whether males and females differ in their responses
      to a similar physical stress task. The aim of this study was to evaluate the
      differences between the psychoneuroimmunological responses of healthy active
      males and females to a high-intensity interval exercise protocol. Fifty healthy
      active subjects (25 females) underwent 2 exercise protocol sessions at least 2
      weeks apart and at the same time of the day. The first session familiarized
      participants with the protocol. In the second, after a baseline measurement,
      subjects performed an exercise protocol with a standardized warm-up followed by
      three 30-s Wingate tests and an active recovery period. Baseline and
      postintervention data were gathered on the following: Holter electrocardiogram
      recordings (standard deviation of normal-to-normal interval [SDNN], square root
      of mean squared differences of successive NN intervals [RMSSD]); heart rate
      variability (HRV) index; salivary total protein and immunoglobulin A levels;
      pressure pain thresholds in masseter and upper trapezius muscles; and profile of
      mood states. After the exercise protocol, mood disturbance was significantly
      greater in the males than in the females, while the salivary immunoglobulin A
      level relative to total proteins was significantly lower in the males. These
      results suggest that high-intensity interval exercise induces a worse
      psychoneuroimmunological state in males than in females.

PMID- 22661641
TI  - Epigenetic regulation and measurement of epigenetic changes.
AB  - Epigenetic mechanisms provide an adaptive layer of control in the regulation of
      gene expression that enables an organism to adjust to a changing environment.
      Epigenetic regulation increases the functional complexity of deoxyribonucleic
      acid (DNA) by altering chromatin structure, nuclear organization, and transcript
      stability. These changes may additively or synergistically influence gene
      expression and result in long-term molecular and functional consequences
      independent of the DNA sequence that may ultimately define an individual's
      phenotype. This article (1) describes histone modification, DNA methylation, and
      expression of small noncoding RNA species; (2) reviews the most common methods
      used to measure these epigenetic changes; and (3) presents factors that need to
      be considered when choosing a specific tissue to evaluate for epigenetic changes.

PMID- 22661643
TI  - Genetic and environmental determinants for disease risk in subsets of rheumatoid
      arthritis defined by the anticitrullinated protein/peptide antibody fine
      specificity profile.
AB  - OBJECTIVES: To increase understanding of the aetiology and pathogenesis of
      rheumatoid arthritis (RA), genetic and environmental risk factors for RA subsets,
      defined by the presence or absence of different anticitrullinated protein/peptide
      antibodies (ACPAs) targeting citrullinated peptides from alpha-enolase, vimentin,
      fibrinogen and collagen type II, were investigated. METHODS: 1985 patients with
      RA and 2252 matched controls from the EIRA case-control cohort were used in the
      study. Serum samples were assayed by ELISA for the presence of anticyclic
      citrullinated peptides (anti-CCP) antibodies and four different ACPA fine
      specificities. Cross-reactivity between ACPAs was examined by peptide absorption
      experiments. Genotyping was performed for HLA-DRB1 shared epitope (SE) alleles
      and the PTPN22 gene, while information regarding smoking was obtained by
      questionnaire. The association of genetic and environmental risk factors with
      different subsets of RA was calculated by logistic regression analysis. RESULTS:
      Limited cross-reactivity was observed between different ACPA fine specificities.
      In total, 17 RA subsets could be identified based on their different ACPA fine
      specificity profiles. Large differences in association with genetic and
      environmental determinants were observed between subsets. The strongest
      association of HLA-DRB1 SE, PTPN22 and smoking was identified for the RA subset
      which was defined by the presence of antibodies to citrullinated alpha-enolase
      and vimentin. CONCLUSION: This study provides the most comprehensive picture to
      date of how HLA-DRB1 SE, PTPN22 and smoking are associated with the presence of
      specific ACPA reactivities rather than anti-CCP levels. The new data will form a
      basis for molecular studies aimed at understanding disease development in
      serologically distinct subsets of RA.

PMID- 22661644
TI  - Genetic markers of rheumatoid arthritis susceptibility in anti-citrullinated
      peptide antibody negative patients.
AB  - INTRODUCTION: There are now over 30 confirmed loci predisposing to rheumatoid
      arthritis (RA). Studies have been largely undertaken in patients with anticyclic
      citrullinated peptide (anti-CCP) positive RA, and some genetic associations
      appear stronger in this subgroup than in anti-CCP negative disease, although few
      studies have had adequate power to address the question. The authors therefore
      investigated confirmed RA susceptibility loci in a large cohort of anti-CCP
      negative RA subjects. METHODS: RA patients and controls, with serological and
      genetic data, were available from UK Caucasian patients (n=4068 anti-CCP
      positive, 2040 anti-CCP negative RA) and 13,009 healthy controls. HLA-DRB1
      genotypes and 36 single nucleotide polymorphisms were tested for association
      between controls and anti-CCP positive or negative RA. RESULTS: The shared
      epitope (SE) showed a strong association with anti-CCP positive and negative RA,
      although the effect size was significantly lower in the latter (effect size
      ratio=3.18, p<1.0E-96). A non-intronic marker at TNFAIP3, GIN1/C5orf30, STAT4,
      ANKRD55/IL6ST, BLK and PTPN22 showed association with RA susceptibility,
      irrespective of the serological status, the latter three markers remaining
      significantly associated with anti-CCP negative RA, after correction for multiple
      testing. No significant association with anti-CCP negative RA was detected for
      other markers (eg, AFF3, CD28, intronic marker at TNFAIP3), though the study
      power for those markers was over 80%. DISCUSSION: In the largest sample size
      studied to date, the authors have shown that the strength of association, the
      effect size and the number of known RA susceptibility loci associated with
      disease is different in the two disease serotypes, confirming the hypothesis that
      they might be two genetically different subsets.

PMID- 22661645
TI  - Guidelines for the genetic diagnosis of hereditary recurrent fevers.
AB  - Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory
      diseases characterised by recurrent bouts of fever and serosal inflammation that
      are caused by pathogenic variants in genes important for the regulation of innate
      immunity. Discovery of the molecular defects responsible for these diseases has
      initiated genetic diagnostics in many countries around the world, including the
      Middle East, Europe, USA, Japan and Australia. However, diverse testing methods
      and reporting practices are employed and there is a clear need for consensus
      guidelines for HRF genetic testing. Draft guidelines were prepared based on
      current practice deduced from previous HRF external quality assurance schemes and
      data from the literature. The draft document was disseminated through the
      European Molecular Genetics Quality Network for broader consultation and
      amendment. A workshop was held in Bruges (Belgium) on 18 and 19 September 2011 to
      ratify the draft and obtain a final consensus document. An agreed set of best
      practice guidelines was proposed for genetic diagnostic testing of HRFs, for
      reporting the genetic results and for defining their clinical significance.

PMID- 22661646
TI  - Intravenous golimumab is effective in patients with active rheumatoid arthritis
      despite methotrexate therapy with responses as early as week 2: results of the
      phase 3, randomised, multicentre, double-blind, placebo-controlled GO-FURTHER
      trial.
AB  - OBJECTIVES: Evaluate the efficacy of intravenous golimumab 2 mg/kg+methotrexate
      (MTX) in patients with active rheumatoid arthritis (RA) receiving MTX. METHODS:
      Patients (n=592) with active disease (>=6/66 swollen, >=6/68 tender joints, C
      reactive protein >=1.0 mg/dl, rheumatoid factor positive and/or anticyclic
      citrullinated protein antibody positive at screening) despite MTX (15-25 mg/week)
      participated in this double-blind, placebo-controlled, phase 3 study. Patients
      were randomised (2:1) to receive intravenous golimumab 2 mg/kg, or placebo
      infusions at weeks 0 and 4 and every (q) 8 weeks; patients continued MTX. Placebo
      patients with <10% improvement in combined swollen/tender joint counts at week 16
      could early escape to intravenous golimumab 2 mg/kg. The primary endpoint was
      week 14 American College of Rheumatology 20% (ACR20) response. Analyses employed
      non-responder imputation and last-observation-carried-forward. RESULTS: At week
      14, significantly (p<0.001) larger proportions of golimumab+MTX than placebo+MTX
      patients achieved ACR20 response (59% vs 25%, respectively), a disease activity
      score of good/moderate (EULAR) response (81% vs 40%), and greater median
      improvement in health assessment questionnaire scores (0.500 vs 0.125).
      Improvements versus placebo+MTX were observed by week 2. Similar proportions of
      patients receiving golimumab+MTX and placebo+MTX, respectively, reported adverse
      events through week 16 (47% and 44%) and week 24 (53% and 49%). Serious adverse
      events were reported by more golimumab+MTX (4.1%) than placebo+MTX (2%) patients
      at week 24. CONCLUSION: The addition of intravenous golimumab rapidly and
      significantly improved signs and symptoms in patients with active RA despite
      ongoing MTX, in some patients by week 2.

PMID- 22661647
TI  - BioMercator V3: an upgrade of genetic map compilation and quantitative trait loci
      meta-analysis algorithms.
AB  - SUMMARY: Compilation of genetic maps combined to quantitative trait loci (QTL)
      meta-analysis has proven to be a powerful approach contributing to the
      identification of candidate genes underlying quantitative traits. BioMercator was
      the first software offering a complete set of algorithms and visualization tool
      covering all steps required to perform QTL meta-analysis. Despite several
      limitations, the software is still widely used. We developed a new version
      proposing additional up to date methods and improving graphical representation
      and exploration of large datasets. AVAILABILITY AND IMPLEMENTATION: BioMercator
      V3 is implemented in JAVA and freely available
      (http://moulon.inra.fr/biomercator) CONTACT: joets@moulon.inra.fr.

PMID- 22661648
TI  - POOL server: machine learning application for functional site prediction in
      proteins.
AB  - SUMMARY: We present an automated web server for partial order optimum likelihood
      (POOL), a machine learning application that combines computed electrostatic and
      geometric information for high-performance prediction of catalytic residues from
      3D structures. Input features consist of THEMATICS electrostatics data and pocket
      information from ConCavity. THEMATICS measures deviation from typical, sigmoidal
      titration behavior to identify functionally important residues and ConCavity
      identifies binding pockets by analyzing the surface geometry of protein
      structures. Both THEMATICS and ConCavity (structure only) do not require the
      query protein to have any sequence or structure similarity to other proteins.
      Hence, POOL is applicable to proteins with novel folds and engineered proteins.
      As an additional option for cases where sequence homologues are available, users
      can include evolutionary information from INTREPID for enhanced accuracy in site
      prediction. AVAILABILITY: The web site is free and open to all users with no
      login requirements at http://www.pool.neu.edu. CONTACT: m.ondrechen@neu.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 22661649
TI  - MobiDB: a comprehensive database of intrinsic protein disorder annotations.
AB  - MOTIVATION: Disordered protein regions are key to the function of numerous
      processes within an organism and to the determination of a protein's biological
      role. The most common source for protein disorder annotations, DisProt, covers
      only a fraction of the available sequences. Alternatively, the Protein Data Bank
      (PDB) has been mined for missing residues in X-ray crystallographic structures.
      Herein, we provide a centralized source for data on different flavours of
      disorder in protein structures, MobiDB, building on and expanding the content
      provided by already existing sources. In addition to the DisProt and PDB X-ray
      structures, we have added experimental information from NMR structures and five
      different flavours of two disorder predictors (ESpritz and IUpred). These are
      combined into a weighted consensus disorder used to classify disordered regions
      into flexible and constrained disorder. Users are encouraged to submit manual
      annotations through a submission form. MobiDB features experimental annotations
      for 17 285 proteins, covering the entire PDB and predictions for the SwissProt
      database, with 565 200 annotated sequences. Depending on the disorder flavour, 6
      20% of the residues are predicted as disordered. AVAILABILITY: The database is
      freely available at http://mobidb.bio.unipd.it/. CONTACT:
      silvio.tosatto@unipd.it.

PMID- 22661650
TI  - Long-term results of intravitreal bevacizumab for choroidal neovascularisation in
      pathological myopia.
AB  - AIM: To evaluate the long-term results and prognostic factors of intravitreal
      bevacizumab (IVB) for myopic choroidal neovascularisation (mCNV). METHODS: Thirty
      two eyes of 30 patients with mCNV were included in a prospective case series.
      Treatment consisted of three monthly 1.25 mg IVB injections. Best corrected
      visual acuity (BCVA) and CNV area were compared before and after treatment.
      Prognostic factors included in the regression analyses were age, axial length,
      baseline BCVA, pretreatment CNV area, CNV location and peripapillary atrophy
      area. RESULTS: Results were evaluated at 2 years for 32 eyes and at 3 years for
      27 eyes. Mean (+/- SD) baseline BCVA had improved significantly from 30.1 (+/-
      15.6) letters to 45.4 (+/- 13.0) letters at 3 years (p<0.0001), with a better
      outcome in eyes with juxtafoveal CNV (40.4 +/- 13.5 vs. 54.0 +/- 5.8, p=0.001).
      Baseline BCVA correlated positively with final BCVA (beta= 0.560, p=0.001), while
      age showed a negative correlation (beta= -0.399, p=0.01). CNV area decreased from
      0.63 (+/- 0.71) mm(2) at baseline to 0.40 (+/- 0.57) mm(2) at 3 years (p<0.0001).
      Peripapillary atrophy area was the only significant contributing determinant for
      re-treatment (OR 1.20, 95% CI 1.01 to 1.42, p=0.04). CONCLUSIONS: A regimen of
      three monthly IVB injections yielded effective and sustained results in the
      treatment of mCNV at 3 years of follow-up. Initial BCVA and age were the factors
      that correlated independently with BCVA outcome.

PMID- 22661652
TI  - Nanophthalmos: quantitative analysis of anterior chamber angle configuration
      before and after cataract surgery.
AB  - BACKGROUND/AIMS: To analyse quantitatively the anterior segment configuration in
      eyes with nanophthalmos before and after cataract surgery. METHODS: This was a
      retrospective, non-comparative, interventional case series. Eleven eyes in eight
      patients with nanophthalmos who underwent phacoemulsification and intraocular
      lens implantation were identified from the department's surgical log, and their
      clinical records were retrospectively reviewed. Main outcome measures were as
      follows: visual acuity, intraocular pressure (IOP), axial length and the
      following ultrasound biomicroscopy parameters: angle opening distance at 500 MUm
      anterior to the scleral spur (AOD500), trabecular-iris angle (TIA) and trabecular
      ciliary process distance. RESULTS: The mean axial length of the eyes was 17.3 +/-
      1.7 mm. AOD500 and TIA increased after cataract surgery (p<0.005). Smaller axial
      length, AOD500 and TIA before cataract surgery were observed in eyes with
      preoperative IOP elevation than those without preoperative IOP elevation
      (p<0.05). Lower postoperative IOP was correlated with greater AOD500 and TIA
      before cataract surgery (p<0.05). CONCLUSIONS: Cataract surgery deepened the
      anterior chamber and widened the anterior chamber angle in nanophthalmic eyes.
      Cataract surgery may have beneficial effects on IOP in eyes with nanophthalmos.

PMID- 22661653
TI  - Anti-inflammatory effect of quercetin in a whole orbital tissue culture of
      Graves' orbitopathy.
AB  - PURPOSE: The authors previously reported that quercetin significantly inhibits
      interleukin (IL)-1beta-induced increases of proinflammatory cytokines in cultured
      primary orbital fibroblasts from Graves' orbitopathy (GO). This study
      investigated the inhibitory effect of quercetin on inflammation in cultured whole
      orbital tissue. METHODS: Orbital fat tissues from GO and normal samples were
      cultured with or without non-toxic concentrations of quercetin. Lactate
      dehydrogenase (LDH) release was used to identify non-toxic concentrations of
      quercetin. IL-6, IL-8, IL-1alpha, IL-1beta and tumour necrosis factor alpha
      (TNFalpha) proteins were measured in tissue culture supernatants by ELISA, and
      gene transcript levels were determined using quantitative PCR, expressed as
      relative fold changes of threshold cycle value relative to the control group.
      RESULTS: The maximal non-cytotoxic treatment of quercetin was 100 MUM for 72 h,
      based on the considerably low LDH release with these conditions. IL-1beta, IL-6
      and TNFalpha protein levels corrected for tissue weight were significantly higher
      in supernatants of GO samples than normal controls (p<0.05). Quercetin reduced IL
      6, IL-8 and TNFalpha protein production in supernatants of all GO samples (n=4)
      in a dose-dependent manner; however, only the reduction in IL-6 was statistically
      significant (p<0.05). Quercetin had a significant suppression of tissue IL-6, IL
      8, IL-1beta and TNFalpha mRNA expression in cultured orbital tissues from three
      GO samples relative to untreated control tissue (p<0.05). CONCLUSIONS: Inhibition
      of proinflammatory cytokines by the natural product quercetin in both primary
      orbital fibroblasts and tissue culture provides the basis for its potential use
      as an anti-inflammatory agent in the treatment of GO.

PMID- 22661655
TI  - In this issue of Occupational Medicine.

PMID- 22661656
TI  - Hyperglycaemia and cognitive function--acute and chronic effects and work.

PMID- 22661657
TI  - Swimming with sharks: delivering the occupational health message.

PMID- 22661658
TI  - Women bootmakers 1991.

PMID- 22661659
TI  - HIV and employment.
AB  - According to 2009 statistics, the human immunodeficiency virus (HIV) infected an
      estimated 86,500 individuals within the UK, although around one-quarter were
      unaware of their infection. In the majority of cases, it is now considered a long
      term controllable but incurable infection. Indeed, most HIV-positive individuals
      are able to work. Employment is across most, if not all, workforce sectors and
      protection against workplace discrimination is provided by the Equality Act 2010.
      Issues including confidentiality, workplace adjustments, vaccinations and travel
      restrictions may be relevant to the occupational health of HIV-positive workers.
      There are special considerations concerning HIV-infected health care workers,
      including avoidance of performing exposure-prone procedures. Prevention of HIV
      acquisition in the workplace is relevant to a diverse range of occupational
      environments, and HIV post-exposure prophylaxis should be considered after
      potential HIV exposure incidents. If a worker contracts HIV by occupational
      means, financial help may be available.

PMID- 22661661
TI  - Substance misuse among health care workers: national survey of occupational
      physicians.
AB  - BACKGROUND: National Health Service (NHS) occupational health departments assist
      in the identification and assessment of substance-use disorders among health care
      workers (HCWs) and are involved in the management of an individual's return to
      work after treatment. AIMS: To determine the experience and training of NHS
      occupational health physicians (OHPs) in identifying substance misuse among HCWs.
      METHODS: A national, cross-sectional, postal-based questionnaire was administered
      to the Association of National Health Occupational Physicians membership.
      RESULTS: A total of 145/224 (65%) OHPs (55% male), with a mean age of 49 years
      (SD +/- 9.1; range 28-76), who had worked in the NHS on average for 9.6 years
      took part. The majority of respondents were consultant grade (59%). Since taking
      up their NHS post, 26% had received no training in substance misuse. Of those who
      had undergone formal training, the mean duration received was 2.8 days for drugs
      and 3.5 days for alcohol. OHPs reported that they did not feel sufficiently
      trained in this area. Most (65%) did not routinely include standardized screening
      tools or deliver 'brief interventions' (78%), although many reported that they
      would routinely ask about substance use when there was no clear indication of use
      (42%). The majority did not feel they were adequately supported (54%) in this
      work, nor did they have adequate resources for these patients within their
      organization (68%). CONCLUSIONS: OHPs see HCWs with substance-use problems as
      part of their work, but the support provided is likely limited by insufficient
      training and inadequate support.

PMID- 22661662
TI  - CT findings related to exposure to polyvinyl chloride.
AB  - BACKGROUND: Although some adverse health effects of exposure to polyvinyl
      chloride (PVC) are well known, there is limited evidence of its effects on the
      respiratory system. AIMS: To assess the pulmonary effects of exposure to PVC with
      high-resolution computed tomography (HRCT). METHODS: Workers and administrative
      staff of two PVC production plants completed questionnaires and went through
      pulmonary function testing and HRCT. Analysis of PVC dust in the work environment
      was performed by the Directorate of Occupational Health and Safety. RESULTS: In
      total, 104 PVC-exposed workers and 43 administrative controls participated. HRCT
      revealed pleural and/or parenchymal changes in 55% of the exposed subjects.
      Pleural thickening was detected in 14 subjects, 13 of whom were in the exposed
      group (P < 0.05). Isolated pleural thickening without parenchymal involvement was
      present in seven workers, who were all in the exposed group (P < 0.05). Pleural
      thickening was frequently bilateral and localized to the parietal and visceral
      pleura. Round opacities, heterogeneous attenuation and ground-glass opacities
      were only detected in the exposed group (P < 0.05). Exposure to dust increased
      the risk of findings on HRCT (odds ratio (OR) 4.2, P < 0.05). There were no
      correlations between pulmonary function tests or respiratory symptoms and HRCT
      findings. HRCT changes were more common in subjects with forced mid-expiratory
      flow (FEF(25-75)) < 50% (P < 0.001). CONCLUSIONS: This study found that exposure
      to PVC dust, at levels below the legal limit for respirable particulate matter,
      was associated with parenchymal changes and pleural thickening on HRCT.

PMID- 22661663
TI  - Musculoskeletal pain in four occupational populations in Sri Lanka.
AB  - BACKGROUND: Factors influencing work-related musculoskeletal disorders might
      differ in developing and developed countries. AIMS: To assess the prevalence and
      determinants of musculoskeletal pain in four occupational populations in Sri
      Lanka. METHODS: As part of the international Cultural and Psychosocial Influences
      on Disability study, samples of postal workers, sewing machinists, nurses and
      computer operators were interviewed about pain at each of six anatomical sites in
      the past month, and about possible physical and psychosocial risk factors.
      Associations with prevalent pain were assessed by binomial regression. RESULTS:
      Analysis was based on 852 participants (86% response rate). Overall, the lower
      back was the most common site of pain, with 1-month prevalence ranging from 12%
      in computer operators to 30% in nurses. Postal workers had the highest prevalence
      of shoulder pain (23%), but pain in the wrist/hand was relatively uncommon in all
      four occupational groups (prevalence rates ranged from 8% to 9%). Low mood and
      tendency to somatize were consistently associated with pain at all six sites.
      After adjustment for psychosocial risk factors, there was a higher rate of low
      back pain in nurses and postal workers than in computer operators, a higher rate
      of shoulder pain in postal workers than in the other occupational populations,
      and a relatively low rate of knee pain in computer operators. CONCLUSIONS: Rates
      of regional pain, especially at the wrist/hand, were lower than have been
      reported in Western countries. As elsewhere, pain was strongly associated with
      low mood and somatizing tendency. Differences in patterns of pain by occupation
      may reflect differences in physical activities.

PMID- 22661664
TI  - Resources for preventing sickness absence due to low back pain.
AB  - BACKGROUND: After an episode of non-specific low back pain (LBP) some individuals
      fail to return to work. The factors leading to such LBP-related sickness absence
      are not yet fully understood. AIMS: To identify individual resources, over and
      above the already established predictors, for preventing LBP-related sickness
      absence in a population-based sample of workers experiencing an episode of LBP.
      METHODS: Cohort study with 1-year follow-up. Participants were from a working
      population who reported an episode of acute or subacute LBP at baseline. Four
      potential resources-life satisfaction, doing sports, job satisfaction and social
      support at work-were examined for their incremental value in predicting sickness
      absence over and above baseline sickness absence and fear-avoidance beliefs about
      work. RESULTS: In all, 279 workers participated in the study. All four resources
      showed an inverse relationship with regard to sickness absence. A multiple
      regression analysis revealed that life satisfaction as a resource protected
      against sickness absence, when controlling for established risk factors. Job
      satisfaction and social support at work minimized the influence of sickness
      absence at baseline and at 1-year follow-up. CONCLUSIONS: In a non-clinical
      working sample of individuals experiencing an acute/subacute episode of LBP, life
      satisfaction was a unique predictor of sickness absence after 1 year. Prevention
      in the occupational setting should not only address common risk factors but also
      occupational and individual resources that keep workers satisfied with life
      despite having LBP.

PMID- 22661665
TI  - Validation of the Italian version of the HSE Indicator Tool.
AB  - BACKGROUND: An Italian version of the Health & Safety Executive's (HSE)
      Management Standards Revised Indicator Tool (MS-RIT) has been used to monitor the
      working conditions that may lead to stress. AIMS: To initially examine the factor
      structure of the Italian version of the MS-RIT, in comparison with the original
      UK tool, and to investigate its validity and reliability; second, to study the
      association between occupational stress and psychological distress. METHODS:
      Workers from 17 companies self-completed the MS-RIT and the General Health
      Questionnaire used to measure the psychological distress while they waited for
      their periodic examination at the workplace. Factor analysis was employed to
      ascertain whether the Italian version maintained the original subdivision into
      seven scales. Odds ratios were calculated to estimate the risk of impairment
      associated with exposure to stress at the workplace. RESULTS: In total, 748
      workers participated; the response rate was 91%. The factor structure of the
      Italian MS-RIT corresponded partially to the original UK version. The 'demand',
      'control', 'role', ' relationship' and 'colleague-support' scales were equivalent
      to the UK ones. A principal factor, termed ' elasticity', incorporated the UK
      'management-support' and 'change' scales. Reliability analysis of the sub-scales
      revealed Cronbach's alpha values ranging from 0.75 to 0.86. CONCLUSIONS: Our
      findings confirmed the usefulness of the Italian version of the HSE MS-RIT in
      stress control.

PMID- 22661666
TI  - Occupational asthma due to spruce wood.
AB  - Workers exposed to a variety of wood dusts are known to experience work-related
      respiratory symptoms, including occupational asthma. There are, however, few
      reports of occupational asthma due to spruce wood. We present the case of a 31
      year-old sawmill owner with severe asthma caused by exposure to spruce wood dust,
      who developed asthmatic symptoms after 2 years of working. Investigations
      included clinical examination, routine laboratory tests, spirometry, chest X-ray,
      total serum immunoglobulin E (IgE) and specific serum IgEs against various woods
      and other occupational allergens. Additionally, we monitored the peak expiratory
      flow rate (PEFR) and symptom score both at work and when off work. Specific serum
      IgE for spruce wood was detected (7.8 IU/ml). The results of PEFR and workplace
      symptom-score monitoring, coupled with an elevated eosinophil count in induced
      sputum, supported the diagnosis of occupational asthma. To our knowledge, this is
      the first well-documented case of occupational asthma induced by spruce wood
      dust. A type I immunological mechanism seems to be responsible.

PMID- 22661669
TI  - Response to: Self-reporting height and weight.

PMID- 22661670
TI  - Long-term pesticide exposure and the risk of testicular cancer.

PMID- 22661671
TI  - How I use it: Voice recognition software.

PMID- 22661672
TI  - Risk factors and outcome of contamination in patients on peritoneal dialysis--a
      single-center experience of 15 years.
AB  - OBJECTIVE: Contamination is an important risk factor for peritoneal dialysis (PD)
      related peritonitis. The present study outlines the clinical characteristics and
      outcomes of PD patients experiencing touch contamination. METHODS: We reviewed
      the case records of PD patients from 1995 to 2010. Patients who experienced
      contamination of their PD system were identified and stratified into "dry" and
      "wet" contamination groups. Risk factors, microbiology, and clinical outcomes
      were compared. RESULTS: Of 548 episodes of touch contamination, 246 involved dry
      contamination, and 302, wet contamination. After contamination, 17 episodes of
      peritonitis (3.1%) developed; all episodes occurred in the wet contamination
      group (p < 0.001). The incidence of peritonitis after wet contamination was
      5.63%. Prophylactic antibiotics significantly reduced the risk of peritonitis (1
      of 182 episodes, p < 0.001). Half the patients experiencing peritonitis had
      either culture-negative or staphylococcal episodes, and most of those episodes
      responded to intraperitoneal antibiotics. In 2 patients, peritonitis was
      attributable to Pseudomonas, and in 3, to Acinetobacter. In these latter
      patients, outcomes were less favorable, with catheter removal being required in 4
      of the 5 episodes. CONCLUSIONS: The overall rate of peritonitis was low after
      contamination. Wet contamination was associated with a much higher risk of
      peritonitis. Prophylactic antibiotics after wet contamination were effective in
      preventing peritonitis.

PMID- 22661674
TI  - Psychodynamic psychiatry's green shoots.
AB  - Psychodynamic psychiatry makes a significant educational, scientific and
      therapeutic contribution to contemporary psychiatry. Recent developments in gene
      environment interaction, neuropsychoanalysis and the accumulating evidence base
      for psychoanalytic therapies and their implications for practice are reviewed.

PMID- 22661673
TI  - Increased lymphatic vessels in patients with encapsulating peritoneal sclerosis.
AB  - BACKGROUND: The angiogenic response is partly involved in the progression of
      encapsulating peritoneal sclerosis (EPS). However, the details of the angiogenic
      response, especially for lymphatic vessels in patients with EPS, remain unclear.
      In addition, because of technical limitations, morphology studies reported to
      date have examined only the parietal peritoneum. The morphologies of parietal and
      visceral lymphatic vessels in patients with EPS both need to be analyzed.
      METHODS: We examined peritoneal samples from 18 patients with EPS who underwent
      enterolysis of the visceral peritoneum and compared them with samples from 17
      autopsy cases (controls). To examine the angiogenic response, we performed
      immunohistochemistry for the endothelial markers CD34 (blood vessels) and
      podoplanin (lymphatic vessels) and for the cell proliferation marker Ki-67.
      Immunogold electron microscopy analysis for podoplanin was also performed. In 7
      of 18 cases, we compared differences in the angiogenic response of the parietal
      and visceral peritoneal membranes. RESULTS: Angiogenic responses were more
      frequent in the compact zone than in regenerated layers. The number of
      capillaries positive for anti-CD34 and anti-podoplanin monoclonal antibodies per
      unit area of visceral peritoneal tissue was, respectively, 41.1 +/- 29.3/mm(2) in
      EPS patients and 2.7 +/- 4.4/mm(2) in controls (p <= 0.01) and 48.1 +/-
      43.9/mm(2) in EPS patients and 4.1 +/- 5.4/mm(2) in controls (p <= 0.01). The
      percentage of capillaries positive for anti-Ki-67, CD34, and podoplanin was 4.6%
      in EPS patients (p <= 0.01) and 0.8% in controls (p = 0.09). The immunogold
      electron microscopy analysis revealed that podoplanin was localized to
      endothelial cells with anchoring filaments, a specific feature of lymphatic
      vessels. Furthermore, compared with parietal peritoneal membrane, visceral
      peritoneal membrane had a more prominent podoplanin-positive capillary profile,
      but not a prominent CD34-positive capillary profile. In addition, fibroblast-like
      cells double-positive for podoplanin and smooth muscle actin were markedly
      increased in the degenerated layer, as previously reported. CONCLUSIONS: Our
      study demonstrated that lymphatic vessels are increased in the visceral
      peritoneum of patients with EPS.

PMID- 22661675
TI  - Better care for depression in the workplace: integrating occupational and mental
      health services.
AB  - People with depression in the workplace are less productive and at risk of losing
      their job. Many never work again. Intervention should ideally begin before
      sickness absence occurs and early return to work should be the focus of care.
      This will require closer integration of primary care, mental health and
      occupational health services.

PMID- 22661676
TI  - Role of mental health professionals in the management of functional somatic
      symptoms in primary care.
AB  - Functional somatic symptoms associated with persistent frequent attendance is
      emotionally demanding, costly and intractable to treat. Such patients are hard to
      engage in practice and research by mental health professionals, whose main role
      may be indirect training, supporting and advising primary care professionals
      rather than direct patient care.

PMID- 22661677
TI  - Methodology and reporting of systematic reviews and meta-analyses of
      observational studies in psychiatric epidemiology: systematic review.
AB  - BACKGROUND: Relatively little is known of the use of systematic review and
      synthesis methods of non-randomised psychiatric epidemiological studies, which
      play a vital role in aetiological research, planning and policy-making. AIMS: To
      evaluate reviews of psychiatric epidemiological studies of functional mental
      disorders that employed synthesis methods such as systematic review or meta
      analysis, or other forms of quantitative review. METHOD: We searched the
      literature to identify appropriate reviews published during the period 1996 to
      April 2009. Selected reviews were evaluated using published review guidelines.
      RESULTS: We found 106 reviews in total, of which 38 (36%) did not mention method
      of data abstraction from primary studies at all. Many failed to mention study
      quality, publication bias, bias and confounding. In 73 studies that performed a
      meta-analysis, 58 (79%) tested for heterogeneity and of these, 47 found
      significant heterogeneity. Studies that detected heterogeneity made some
      allowance for this. A major obstacle facing reviewers is the wide variation
      between primary studies in the use of instruments to measure outcomes and in
      sampling methods used. CONCLUSIONS: Many deficiencies found in systematic reviews
      are potentially remediable, although synthesis of primary study findings in a
      field characterised by so many sources of heterogeneity will remain challenging.

PMID- 22661678
TI  - Cognitive development in children with 22q11.2 deletion syndrome.
AB  - BACKGROUND: People with 22q11.2 deletion syndrome (velo-cardio-facial syndrome)
      have a 30-fold risk of developing schizophrenia. In the general population the
      schizophrenia phenotype includes a cognitive deficit and a decline in academic
      performance preceding the first episode of psychosis in a subgroup of patients.
      Findings of cross-sectional studies suggest that cognitive abilities may decline
      over time in some children with 22q11.2 deletion syndrome. If confirmed
      longitudinally, this could indicate that one or more genes within 22q11.2 are
      involved in cognitive decline. AIMS: To assess longitudinally the change in IQ
      scores in children with 22q11.2 deletion syndrome. METHOD: Sixty-nine children
      with the syndrome were cognitively assessed two or three times at set ages 5.5
      years, 7.5 years and 9.5 years. RESULTS: A mean significant decline of 9.7 Full
      Scale IQ points was found between ages 5.5 years and 9.5 years. In addition to
      the overall relative decline that occurred when results were scored according to
      age-specific IQ norms, in 10 out of a group of 29 children an absolute decrease
      in cognitive raw scores was found between ages 7.5 years and 9.5 years. The
      decline was not associated with a change in behavioural measures. CONCLUSIONS:
      The finding of cognitive decline can be only partly explained as the result of
      'growing into deficit'; about a third of 29 children showed an absolute loss of
      cognitive faculties. The results underline the importance of early psychiatric
      screening in this population and indicate that further study of the genes at the
      22q11.2 locus may be relevant to understanding the genetic basis of early
      cognitive deterioration.

PMID- 22661679
TI  - Childhood maltreatment and DSM-IV adult mental disorders: comparison of
      prospective and retrospective findings.
AB  - BACKGROUND: Prior research reports stronger associations between childhood
      maltreatment and adult psychopathology when maltreatment is assessed
      retrospectively compared with prospectively, casting doubt on the mental health
      risk conferred by maltreatment and on the validity of retrospective reports.
      AIMS: To investigate associations of psychopathology with prospective v.
      retrospective maltreatment ascertainment. METHOD: A nationally representative
      sample of respondents aged 16-27 years (n = 1413) in New Zealand completed a
      retrospective assessment of maltreatment and DSM-IV mental disorders. Survey data
      were linked with a national child protection database to identify respondents
      with maltreatment records (prospective ascertainment). RESULTS: Childhood
      maltreatment was associated with elevated odds of mood, anxiety and drug
      disorders (odds ratios = 2.1-4.1), with no difference in association strength
      between prospective and retrospective groups. Prospectively ascertained
      maltreatment predicted unfavourable depression course involving early onset,
      chronicity and impairment. CONCLUSIONS: Prospectively and retrospectively
      assessed maltreatment elevated the risk of psychopathology to a similar degree.
      Prospectively ascertained maltreatment predicted a more unfavourable depression
      course.

PMID- 22661680
TI  - Temperature-related deaths in people with psychosis, dementia and substance
      misuse.
AB  - BACKGROUND: Climate change is expected to have significant effects on human
      health, partly through an increase in extreme events such as heatwaves. People
      with mental illness may be at particular risk. AIMS: To estimate risk conferred
      by high ambient temperature on patients with psychosis, dementia and substance
      misuse. METHOD: We applied time-series regression analysis to data from a
      nationally representative primary care cohort study. Relative risk of death per 1
      degrees C increase in temperature was calculated above a threshold. RESULTS:
      Patients with mental illness showed an overall increase in risk of death of 4.9%
      (95% CI 2.0-7.8) per 1 degrees C increase in temperature above the 93rd
      percentile of the annual temperature distribution. Younger patients and those
      with a primary diagnosis of substance misuse demonstrated greatest mortality
      risk. CONCLUSIONS: The increased risk of death during hot weather in patients
      with psychosis, dementia and substance misuse has implications for public health
      strategies during heatwaves.

PMID- 22661681
TI  - Can a 'true' effect be built on a 'wrong' model?

PMID- 22661683
TI  - Effectiveness of cost-effectiveness.

PMID- 22661685
TI  - Growing unculturable bacteria.
AB  - The bacteria that can be grown in the laboratory are only a small fraction of the
      total diversity that exists in nature. At all levels of bacterial phylogeny,
      uncultured clades that do not grow on standard media are playing critical roles
      in cycling carbon, nitrogen, and other elements, synthesizing novel natural
      products, and impacting the surrounding organisms and environment. While
      molecular techniques, such as metagenomic sequencing, can provide some
      information independent of our ability to culture these organisms, it is
      essentially impossible to learn new gene and pathway functions from pure sequence
      data. A true understanding of the physiology of these bacteria and their roles in
      ecology, host health, and natural product production requires their cultivation
      in the laboratory. Recent advances in growing these species include coculture
      with other bacteria, recreating the environment in the laboratory, and combining
      these approaches with microcultivation technology to increase throughput and
      access rare species. These studies are unraveling the molecular mechanisms of
      unculturability and are identifying growth factors that promote the growth of
      previously unculturable organisms. This minireview summarizes the recent
      discoveries in this area and discusses the potential future of the field.

PMID- 22661686
TI  - A tangled web: regulatory connections between quorum sensing and cyclic Di-GMP.
AB  - Bacteria sense and respond to environmental cues to control important
      developmental processes. Two widely conserved and important strategies that
      bacteria employ to sense changes in population density and local environmental
      conditions are quorum sensing (QS) and cyclic di-GMP (c-di-GMP) signaling,
      respectively. The importance of these pathways in controlling a broad variety of
      functions, including virulence, biofilm formation, and motility, has been
      recognized in many species. Recent research has shown that these pathways are
      intricately intertwined. Here we review the regulatory connections between QS and
      c-di-GMP signaling. We propose that the integration of QS with c-di-GMP allows
      bacteria to assimilate information about the local bacterial population density
      with other physicochemical environmental signals within the broader c-di-GMP
      signaling network.

PMID- 22661687
TI  - YqjD is an inner membrane protein associated with stationary-phase ribosomes in
      Escherichia coli.
AB  - Here, we provide evidence that YqjD, a hypothetical protein of Escherichia coli,
      is an inner membrane and ribosome binding protein. This protein is expressed
      during the stationary growth phase, and expression is regulated by stress
      response sigma factor RpoS. YqjD possesses a transmembrane motif in the C
      terminal region and associates with 70S and 100S ribosomes at the N-terminal
      region. Interestingly, E. coli possesses two paralogous proteins of YqjD, ElaB
      and YgaM, which are expressed and bind to ribosomes in a similar manner to YqjD.
      Overexpression of YqjD leads to inhibition of cell growth. It has been suggested
      that YqjD loses ribosomal activity and localizes ribosomes to the membrane during
      the stationary phase.

PMID- 22661688
TI  - Daptomycin-mediated reorganization of membrane architecture causes
      mislocalization of essential cell division proteins.
AB  - Daptomycin is a lipopeptide antibiotic used clinically for the treatment of
      certain types of Gram-positive infections, including those caused by methicillin
      resistant Staphylococcus aureus (MRSA). Details of the mechanism of action of
      daptomycin continue to be elucidated, particularly the question of whether
      daptomycin acts on the cell membrane, the cell wall, or both. Here, we use
      fluorescence microscopy to directly visualize the interaction of daptomycin with
      the model Gram-positive bacterium Bacillus subtilis. We show that the first
      observable cellular effects are the formation of membrane distortions (patches of
      membrane) that precede cell death by more than 30 min. Membrane patches are able
      to recruit the essential cell division protein DivIVA. Recruitment of DivIVA
      correlates with membrane defects and changes in cell morphology, suggesting a
      localized alteration in the activity of enzymes involved in cell wall synthesis
      that could account for previously described effects of daptomycin on cell wall
      morphology and septation. Membrane defects colocalize with fluorescently labeled
      daptomycin, DivIVA, and fluorescent reporters of peptidoglycan biogenesis
      (Bocillin FL and BODIPY FL-vancomycin), suggesting that daptomycin plays a direct
      role in these events. Our results support a mechanism for daptomycin with a
      primary effect on cell membranes that in turn redirects the localization of
      proteins involved in cell division and cell wall synthesis, causing dramatic cell
      wall and membrane defects, which may ultimately lead to a breach in the cell
      membrane and cell death. These results help resolve the longstanding questions
      regarding the mechanism of action of this important class of antibiotics.

PMID- 22661690
TI  - Stable isotope peptide mass spectrometry to decipher amino acid metabolism in
      Dehalococcoides strain CBDB1.
AB  - Dehalococcoides species are key players in the anaerobic transformation of
      halogenated solvents at contaminated sites. Here, we analyze isotopologue
      distributions in amino acid pools from peptides of Dehalococcoides strain CBDB1
      after incubation with (13)C-labeled acetate or bicarbonate as a carbon source.
      The resulting data were interpreted with regard to genome annotations to identify
      amino acid biosynthesis pathways. In addition to using gas chromatography-mass
      spectrometry (GC-MS) for analyzing derivatized amino acids after protein
      hydrolysis, we introduce a second, much milder method, in which we directly
      analyze peptide masses after tryptic digest and peptide fragments by nano-liquid
      chromatography-electrospray ionization-tandem mass spectrometry (nano-LC-ESI
      MS/MS). With this method, we identify isotope incorporation patterns for 17
      proteinaceous amino acids, including proline, cysteine, lysine, and arginine,
      which escaped previous analyses in Dehalococcoides. Our results confirmed lysine
      biosynthesis via the alpha-aminoadipate pathway, precluding lysine formation from
      aspartate. Similarly, the isotopologue pattern obtained for arginine provided
      biochemical evidence of its synthesis from glutamate. Direct peptide MS/MS
      analysis of the labeling patterns of glutamine and asparagine, which were
      converted to glutamate and aspartate during protein hydrolysis, gave biochemical
      evidence of their precursors and confirmed glutamate biosynthesis via a Re
      specific citrate synthase. By addition of unlabeled free amino acids to labeled
      cells, we show that in strain CBDB1 none of the 17 tested amino acids was
      incorporated into cell mass, indicating that they are all synthesized de novo.
      Our approach is widely applicable and provides a means to analyze amino acid
      metabolism by studying specific proteins even in mixed consortia.

PMID- 22661689
TI  - Comparative investigation of the genomic regions involved in antigenic variation
      of the TprK antigen among treponemal species, subspecies, and strains.
AB  - Although the three Treponema pallidum subspecies (T. pallidum subsp. pallidum, T.
      pallidum subsp. pertenue, and T. pallidum subsp. endemicum), Treponema
      paraluiscuniculi, and the unclassified Fribourg-Blanc treponeme cause clinically
      distinct diseases, these pathogens are genetically and antigenically highly
      related and are able to cause persistent infection. Recent evidence suggests that
      the putative surface-exposed variable antigen TprK plays an important role in
      both treponemal immune evasion and persistence. tprK heterogeneity is generated
      by nonreciprocal gene conversion between the tprK expression site and donor
      sites. Although each of the above-mentioned species and subspecies has a
      functional tprK antigenic variation system, it is still unclear why the level of
      expression and the rate at which tprK diversifies during infection can differ
      significantly among isolates. To identify genomic differences that might affect
      the generation and expression of TprK variants among these pathogens, we
      performed comparative sequence analysis of the donor sites, as well as the tprK
      expression sites, among eight T. pallidum subsp. pallidum isolates (Nichols Gen,
      Nichols Sea, Chicago, Sea81-4, Dal-1, Street14, UW104, and UW126), three T.
      pallidum subsp. pertenue isolates (Gauthier, CDC2, and Samoa D), one T. pallidum
      subsp. endemicum isolate (Iraq B), the unclassified Fribourg-Blanc isolate, and
      the Cuniculi A strain of T. paraluiscuniculi. Synteny and sequence conservation,
      as well as deletions and insertions, were found in the regions harboring the
      donor sites. These data suggest that the tprK recombination system is harbored
      within dynamic genomic regions and that genomic differences might be an important
      key to explain discrepancies in generation and expression of tprK variants among
      these Treponema isolates.

PMID- 22661691
TI  - SrfJ, a Salmonella type III secretion system effector regulated by PhoP, RcsB,
      and IolR.
AB  - Virulence-related type III secretion systems are present in many Gram-negative
      bacterial pathogens. These complex devices translocate proteins, called
      effectors, from the bacterium into the eukaryotic host cell. Here, we identify
      the product of srfJ, a Salmonella enterica serovar Typhimurium gene regulated by
      SsrB, as a new substrate of the type III secretion system encoded by Salmonella
      pathogenicity island 2. The N-terminal 20-amino-acid segment of SrfJ was
      recognized as a functional secretion and translocation signal specific for this
      system. Transcription of srfJ was positively regulated by the PhoP/PhoQ system in
      an SsrB-dependent manner and was negatively regulated by the Rcs system in an
      SsrB-independent manner. A screen for regulators of an srfJ-lacZ transcriptional
      fusion using the T-POP transposon identified IolR, the regulator of genes
      involved in myo-inositol utilization, as an srfJ repressor. Our results suggest
      that SrfJ is synthesized both inside the host, in response to intracellular
      conditions, and outside the host, in myo-inositol-rich environments.

PMID- 22661692
TI  - Activator role of the pneumococcal Mga-like virulence transcriptional regulator.
AB  - Global transcriptional regulators that respond to specific environmental signals
      are crucial in bacterial pathogenesis. In the case of the Gram-positive pathogen
      Streptococcus pneumoniae (the pneumococcus), the sp1800 gene of the clinical
      isolate TIGR4 encodes a protein that exhibits homology to the Mga "stand-alone"
      response regulator of the group A Streptococcus. Such a pneumococcal protein was
      shown to play a significant role in both nasopharyngeal colonization and
      development of pneumonia in murine infection models. Moreover, it was shown to
      repress the expression of several genes located within the rlrA pathogenicity
      islet. The pneumococcal R6 strain, which derives from the D39 clinical isolate,
      lacks the rlrA islet but has a gene (here named mga(Spn)) equivalent to the
      sp1800 gene. In this work, and using in vivo approaches, we have identified the
      promoter of the mga(Spn) gene (Pmga) and demonstrated that four neighboring open
      reading frames of unknown function (spr1623 to spr1626) constitute an operon.
      Transcription of this operon is under the control of two promoters (P1623A and
      P1623B) that are divergent from the Pmga promoter. Furthermore, we have shown
      that the Mga(Spn) protein activates the P1623B promoter in vivo. This activation
      requires sequences located around 50 to 120 nucleotides upstream of the P1623B
      transcription start site. By DNase I footprinting assays, we have also
      demonstrated that such a region includes an Mga(Spn) binding site. This is the
      first report on the activator role of the pneumococcal Mga-like protein.

PMID- 22661693
TI  - Mycobacterium tuberculosis protein kinase K enables growth adaptation through
      translation control.
AB  - Mycobacterium tuberculosis serine/threonine protein kinases (STPKs) are
      responsible for orchestrating critical metabolic and physiological changes that
      dictate mycobacterial growth adaptation. Previously, we established that PknK
      participates in regulatory pathways that slow the growth of M. tuberculosis in a
      variety of in vitro stress environments and during persistent infection in mice.
      In the present study, we have elaborated on the mechanism of PknK-mediated
      regulation. Through transcription profiling of wild-type H37Rv and a DeltapknK
      mutant strain during logarithmic and stationary growth phases, we determined that
      PknK regulates the expression of a large subset of tRNA genes so that regulation
      is synchronized with growth phase and cellular energy status. Elevated levels of
      wild-type M. tuberculosis PknK (PknK(Mtb)), but not phosphorylation-defective
      PknK(Mtb), in Mycobacterium smegmatis cause significant retardation of the growth
      rate and altered colony morphology. We investigated a role for PknK in
      translational control and established that PknK directs the inhibition of in
      vitro transcription and translation processes in a phosphorylation-dependent
      manner. Increasing concentrations of ATP or PknK exert cooperative effects and
      enhance the inhibitory function of PknK. Furthermore, truncation and mutational
      analyses of PknK revealed that PknK is autoregulated via intramolecular
      interactions with its C-terminal region. Significantly, the invariant lysine 55
      residue was only essential for activity in the full-length PknK protein, and the
      truncated mutant proteins were active. A model for PknK autoregulation is
      proposed and discussed.

PMID- 22661694
TI  - Returning to the golden age of boxing.

PMID- 22661695
TI  - Why hamstring eccentrics are hamstring essentials.

PMID- 22661696
TI  - Health protection of the Olympic athlete.
AB  - Protection of the athletes' health is a clearly articulated objective of the
      International Olympic Committee. Longitudinal surveillance of injuries and
      illnesses can provide valuable data that may identify high-risk sports and
      disciplines. This is a foundation for introducing tailored preventive measures.
      During the XXIX Summer and XXI Winter Games, comprehensive injury and illness
      recording through the medical staff of the participating National Olympic
      Committees and the sports medicine clinics revealed that between 7% and 11% of
      all athletes incurred an injury or suffered from at least one occurrence of
      illness during the Games. The incidence of injuries and illnesses varied
      substantially between sports. In the future, risk factor and injury mechanism
      analyses in high-risk Olympic sports are essential to better direct injury
      prevention strategies. Concomitantly, periodic health evaluations of athletes
      will be instrumental to optimise health protection.

PMID- 22661697
TI  - Competition injuries in taekwondo: a literature review and suggestions for
      prevention and surveillance.
AB  - OBJECTIVE: To review competition injuries in taekwondo and use this information
      to develop recommendations to reduce the number and severity of injuries in
      taekwondo competition. METHODS: The available literature was searched for
      prospective studies on taekwondo injuries in adult athletes. An injury was
      defined as any circumstance for which the athlete sought the assistance of the on
      site medical personnel. Injury rates were expressed per athlete-exposures (A-E)
      and 95% CIs calculated. RESULTS: Total injury rates for elite men varied from
      20.6/1000 A-E (95% CI 11.8 to 29.3) to 139.5/1000 A-E (95% CI 94.0 to 185.1). For
      elite women, the rates varied from 25.3/1000 A-E (95% CI 3.1 to 47.4) to
      105.5/1000 A-E (95% CI 89.8 to 121.1). About one-third of all injuries (29.6%) in
      the men were to the head and neck region, while almost half of the injuries
      (44.5%) were to the lower extremities. In women, 15.2% of injuries were to the
      head and neck and 53.1% to the lower extremities. The vast majority of all
      injuries were contusions (42.7% in the men and 62.7% in the women). Point
      estimates of rates of head injuries and concussions were found to be higher in
      taekwondo than in other contact sports such as football (soccer) and American
      gridiron football. Time-loss injury rates in the men varied from 6.9/1000 A-E
      (95% CI 1.8 to 11.9) to 33.6/1000 A-E (95% CI 18.9 to 48.3). In the women, they
      varied from 2.4/1000 A-E (95% CI 2.3 to 7.2) to 23.0/1000 A-E (95% CI 15.7 to
      30.4). The turning kick was most often involved in causing injury: 56.9% of all
      injuries in the men and 49.8% in the women. Lack of blocking skills was
      identified as one of the main injury mechanisms. CONCLUSIONS: Rule changes should
      be considered and it is recommended that governing bodies employ qualified
      medical personnel. Establishing an ongoing injury surveillance system in
      taekwondo should be the first priority.

PMID- 22661698
TI  - Impaired natural killer cell self-education and "missing-self" responses in Ly49
      deficient mice.
AB  - Ly49-mediated recognition of MHC-I molecules on host cells is considered vital
      for natural killer (NK)-cell regulation and education; however, gene-deficient
      animal models are lacking because of the difficulty in deleting this large
      multigene family. Here, we describe NK gene complex knockdown (NKC(KD)) mice that
      lack expression of Ly49 and related MHC-I receptors on most NK cells. NKC(KD) NK
      cells exhibit defective killing of MHC-I-deficient, but otherwise normal, target
      cells, resulting in defective rejection by NKC(KD) mice of transplants from
      various types of MHC-I-deficient mice. Self-MHC-I immunosurveillance by NK cells
      in NKC(KD) mice can be rescued by self-MHC-I-specific Ly49 transgenes. Although
      NKC(KD) mice display defective recognition of MHC-I-deficient tumor cells,
      resulting in decreased in vivo tumor cell clearance, NKG2D- or antibody-dependent
      cell-mediated cytotoxicity-induced tumor cell cytotoxicity and cytokine
      production induced by activation receptors was efficient in Ly49-deficient NK
      cells, suggesting MHC-I education of NK cells is a single facet regulating their
      total potential. These results provide direct genetic evidence that Ly49
      expression is necessary for NK-cell education to self-MHC-I molecules and that
      the absence of these receptors leads to loss of MHC-I-dependent "missing-self"
      immunosurveillance by NK cells.

PMID- 22661699
TI  - Expression of CD30 in patients with acute graft-versus-host disease.
AB  - Acute GVHD (aGVHD) remains a major source of morbidity after allogeneic
      hematopoietic cell transplantation. CD30 is a cell-surface protein expressed on
      certain activated T cells. We analyzed CD30 expression on peripheral blood T-cell
      subsets and soluble CD30 levels in 26 patients at the time of presentation of
      aGVHD, before the initiation of treatment, compared with 27 patients after
      hematopoietic cell transplantation without aGVHD (NONE). Analysis by flow
      cytometry showed that patients with aGVHD had a greater percentage of CD30
      expressing CD8(+) T cells with the difference especially pronounced in the
      central memory subset (CD8(+)CD45RO(+)CD62L(+)): GVHD median 12.4% (range, 0.8%
      33.4%) versus NONE 2.1% (0.7%, 17.5%), P < .001. There were similar levels of
      CD30 expression in naive T cells, CD4(+) T cells, and regulatory
      (CD4(+)CD127(low)CD25(+)) T cells. Plasma levels of soluble CD30 were
      significantly greater in patients with GVHD: median 61.7 ng/mL (range, 9.8-357.1
      ng/mL) versus 17.4 (range, 3.7-142.4 ng/mL) in NONE (P < .001).
      Immunohistochemical analysis of affected intestinal tissue showed many CD30(+)
      infiltrating lymphocytes present. These results suggest that CD30 expression on
      CD8(+) T-cell subsets or plasma levels of soluble CD30 may be a potential
      biomarker for aGVHD. CD30 may also represent a target for novel therapeutic
      approaches for aGVHD.

PMID- 22661701
TI  - Immunoregulation through extracellular nucleotides.
AB  - Extracellular ATP (eATP), the most abundant among nucleotides, can act as a
      mediator during inflammatory responses by binding to plasmamembrane P2 purinergic
      receptors, which are widely expressed on cells of the immune system. eATP is
      generally considered as a classical danger signal, which stimulates immune
      responses in the presence of tissue damage. Converging evidence from several
      studies using murine models of chronic inflammation have supported this
      hypothesis; however, the role of eATP in the regulation of human immune function
      appears to be more complex. Chronic stimulation with micromolar eATP
      concentrations inhibits the proliferation of T and NK lymphocytes and enhances
      the capacity of dendritic cells to promote tolerance. The effect of eATP depends
      on multiple factors, such as the extent of stimulation, eATP concentration,
      presence/absence of other mediators in the microenvironment, and pattern of P2
      receptor engagement. Small but significant differences in the pattern of P2
      receptor expression in mice and humans confer the diverse capacities of ATP in
      regulating the immune response. Such diversity, which is often overlooked, should
      therefore be carefully considered when evaluating the role of eATP in human
      inflammatory and autoimmune diseases.

PMID- 22661700
TI  - Ly6G ligation blocks recruitment of neutrophils via a beta2-integrin-dependent
      mechanism.
AB  - Ly6G is a glycosylphosphatidylinositol (GPI)-anchored protein of unknown function
      that is commonly targeted to induce experimental neutrophil depletion in mice. In
      the present study, we found that doses of anti-Ly6G Abs too low to produce
      sustained neutropenia remained capable of inhibiting experimental arthritis,
      leaving joint tissues free of infiltrating neutrophils. Thioglycollate-stimulated
      peritonitis was also attenuated. No alteration in neutrophil apoptosis was
      observed, implicating impaired recruitment. Indeed, Ly6G ligation abrogated
      neutrophil migration toward LTB(4) and other chemoattractants in a transwell
      system. Exploring the basis for this blockade, we identified colocalization of
      Ly6G and beta2-integrins by confocal microscopy and confirmed close association
      by both coimmunoprecipitation and fluorescence lifetime imaging microscopy. Anti
      Ly6G Ab impaired surface expression of beta2-integrins in LTB(4)-stimulated
      neutrophils and mimicked CD11a blockade in inhibiting both ICAM-1 binding and
      firm adhesion to activated endothelium under flow conditions. Correspondingly,
      migration of beta2-integrin-deficient neutrophils was no longer inhibited by anti
      Ly6G. These results demonstrate that experimental targeting of Ly6G has
      functional effects on the neutrophil population and identify a previously
      unappreciated role for Ly6G as a modulator of neutrophil migration to sites of
      inflammation via a beta2-integrin-dependent mechanism.

PMID- 22661703
TI  - Functional characterization of the FoxE iron oxidoreductase from the
      photoferrotroph Rhodobacter ferrooxidans SW2.
AB  - Photoferrotrophy is presumed to be an ancient type of photosynthetic metabolism
      in which bacteria use the reducing power of ferrous iron to drive carbon
      fixation. In this work the putative iron oxidoreductase of the photoferrotroph
      Rhodobacter ferrooxidans SW2 was cloned, purified, and characterized for the
      first time. This protein, FoxE, was characterized using spectroscopic,
      thermodynamic, and kinetic techniques. It is a c-type cytochrome that forms a
      trimer or tetramer in solution; the two hemes of each monomer are hexacoordinated
      by histidine and methionine. The hemes have positive reduction potentials that
      allow downhill electron transfer from many geochemically relevant ferrous iron
      forms to the photosynthetic reaction center. The reduction potentials of the
      hemes are different and are cross-assigned to fast and slow kinetic phases of
      ferrous iron oxidation in vitro. Lower reactivity was observed at high pH and may
      contribute to prevent ferric iron precipitation inside or at the surface of the
      cell. These results help fill in the molecular details of a metabolic process
      that likely contributed to the deposition of precambrian banded iron formations,
      globally important sedimentary rocks that are found on every continent today.

PMID- 22661702
TI  - Tissue factor promotes activation of coagulation and inflammation in a mouse
      model of sickle cell disease.
AB  - Sickle cell disease (SCD) is associated with a complex vascular pathophysiology
      that includes activation of coagulation and inflammation. However, the crosstalk
      between these 2 systems in SCD has not been investigated. Here, we examined the
      role of tissue factor (TF) in the activation of coagulation and inflammation in 2
      different mouse models of SCD (BERK and Townes). Leukocytes isolated from BERK
      mice expressed TF protein and had increased TF activity compared with control
      mice. We found that an inhibitory anti-TF antibody abrogated the activation of
      coagulation but had no effect on hemolysis or anemia. Importantly, inhibition of
      TF also attenuated inflammation and endothelial cell injury as demonstrated by
      reduced plasma levels of IL-6, serum amyloid P, and soluble vascular cell
      adhesion molecule-1. In addition, we found decreased levels of the chemokines MCP
      1 and KC, as well as myeloperoxidase in the lungs of sickle cell mice treated
      with the anti-TF antibody. Finally, we found that endothelial cell-specific
      deletion of TF had no effect on coagulation but selectively attenuated plasma
      levels of IL-6. Our data indicate that different cellular sources of TF
      contribute to activation of coagulation, vascular inflammation, and endothelial
      cell injury. Furthermore, it appears that TF contributes to these processes
      without affecting intravascular hemolysis.

PMID- 22661704
TI  - Myosin regulatory light chain diphosphorylation slows relaxation of arterial
      smooth muscle.
AB  - The principal signal to activate smooth muscle contraction is phosphorylation of
      the regulatory light chains of myosin (LC(20)) at Ser(19) by Ca(2+)/calmodulin
      dependent myosin light chain kinase. Inhibition of myosin light chain phosphatase
      leads to Ca(2+)-independent phosphorylation at both Ser(19) and Thr(18) by
      integrin-linked kinase and/or zipper-interacting protein kinase. The functional
      effects of phosphorylation at Thr(18) on steady-state isometric force and
      relaxation rate were investigated in Triton-skinned rat caudal arterial smooth
      muscle strips. Sequential phosphorylation at Ser(19) and Thr(18) was achieved by
      treatment with adenosine 5'-O-(3-thiotriphosphate) in the presence of Ca(2+),
      which induced stoichiometric thiophosphorylation at Ser(19), followed by
      microcystin (phosphatase inhibitor) in the absence of Ca(2+), which induced
      phosphorylation at Thr(18). Phosphorylation at Thr(18) had no effect on steady
      state force induced by Ser(19) thiophosphorylation. However, phosphorylation of
      Ser(19) or both Ser(19) and Thr(18) to comparable stoichiometries (0.5 mol of
      P(i)/mol of LC(20)) and similar levels of isometric force revealed differences in
      the rates of dephosphorylation and relaxation following removal of the stimulus:
      t(&frac12;) values for dephosphorylation were 83.3 and 560 s, and for relaxation
      were 560 and 1293 s, for monophosphorylated (Ser(19)) and diphosphorylated
      LC(20), respectively. We conclude that phosphorylation at Thr(18) decreases the
      rates of LC(20) dephosphorylation and smooth muscle relaxation compared with
      LC(20) phosphorylated exclusively at Ser(19). These effects of LC(20)
      diphosphorylation, combined with increased Ser(19) phosphorylation (Ca(2+)
      independent), may underlie the hypercontractility that is observed in response to
      certain physiological contractile stimuli, and under pathological conditions such
      as cerebral and coronary arterial vasospasm, intimal hyperplasia, and
      hypertension.

PMID- 22661705
TI  - A novel target of microRNA-29, Ring1 and YY1-binding protein (Rybp), negatively
      regulates skeletal myogenesis.
AB  - Skeletal muscle cell differentiation (myogenesis) is a process orchestrated by a
      complex network involving transcription factors, epigenetic regulators, and
      microRNAs. Previous studies identified miR-29 as a pro-myogenic factor that
      interacts with components of Polycomb repressive complex, YY1 and Ezh2. In a
      genome-wide survey of miR-29-mediated transcriptome changes in C2C12 myoblasts,
      many epigenetic factors were found to be down-regulated by miR-29. Among them,
      Rybp was shown to be a direct target of miR-29 through binding to its 3' UTR.
      Functional studies demonstrated that Rybp is down-regulated during myogenesis and
      acts as a negative regulator of skeletal myogenesis both in vitro during C2C12
      differentiation and in vivo in injury-induced muscle regeneration. Furthermore,
      we found that Rybp and YY1 co-occupy several myogenic loci, including miR-29
      itself, to silence their expression, thus forming a Rybp-miR-29 feedback loop.
      Rybp overexpression was found to enhance the enrichment of Ezh2 and
      trimethylation of H3K27 at target loci, suggesting it may facilitate the
      recruitment or stabilization of the Polycomb repressive complex. Collectively,
      our results identify Rybp as a novel regulator of myogenesis that co-acts with
      YY1 to silence miR-29 and other myogenic loci.

PMID- 22661706
TI  - Headless Myo10 is a negative regulator of full-length Myo10 and inhibits axon
      outgrowth in cortical neurons.
AB  - Myo10 is an unconventional myosin that localizes to and induces filopodia,
      structures that are critical for growing axons. In addition to the ~240-kDa full
      length Myo10, brain expresses a ~165 kDa isoform that lacks a functional motor
      domain and is known as headless Myo10. We and others have hypothesized that
      headless Myo10 acts as an endogenous dominant negative of full-length Myo10, but
      this hypothesis has not been tested, and the function of headless Myo10 remains
      unknown. We find that cortical neurons express both headless and full-length
      Myo10 and report the first isoform-specific localization of Myo10 in brain, which
      shows enrichment of headless Myo10 in regions of proliferating and migrating
      cells, including the embryonic ventricular zone and the postnatal rostral
      migratory stream. We also find that headless and full-length Myo10 are expressed
      in embryonic and neuronal stem cells. To directly test the function of headless
      and full-length Myo10, we used RNAi specific to each isoform in mouse cortical
      neuron cultures. Knockdown of full-length Myo10 reduces axon outgrowth, whereas
      knockdown of headless Myo10 increases axon outgrowth. To test whether headless
      Myo10 antagonizes full-length Myo10, we coexpressed both isoforms in COS-7 cells,
      which revealed that headless Myo10 suppresses the filopodia-inducing activity of
      full-length Myo10. Together, these results demonstrate that headless Myo10 can
      function as a negative regulator of full-length Myo10 and that the two isoforms
      of Myo10 have opposing roles in axon outgrowth.

PMID- 22661707
TI  - A measurable activation of the bZIP transcription factor Atf1 in a fission yeast
      strain devoid of stress-activated and cell integrity mitogen-activated protein
      kinase (MAPK) activities.
AB  - In Schizosaccharomyces pombe, the stress-activated Sty1 MAPK pathway is essential
      for cell survival under stress conditions. The Sty1 MAPK regulates Atf1
      transcription factor to elicit stress responses in extreme conditions of
      osmolarity and reactive oxygen species-generating agents such as hydrogen
      peroxide, heat, low glucose, and heavy metal. Herein, using a newly developed
      Renilla luciferase reporter assay with enhanced detection sensitivity and
      accuracy, we show that distinct signaling pathways respond to cadmium and other
      reactive oxygen species-generating agents for the activation of Atf1. Also,
      surprisingly, a measurable activation of Atf1 transcription factor was still
      observed devoid of Sty1 MAPK activity. Further genetic and biological analyses
      revealed that the residual activation is caused by the activation of the cell
      wall integrity Pmk1 MAPK pathway and a redox-mediated activation of Atf1.

PMID- 22661708
TI  - A single nucleotide polymorphism in 3'-untranslated region contributes to the
      regulation of Toll-like receptor 4 translation.
AB  - We have previously shown that a single nucleotide polymorphism rs11536889 in the
      3'-untranslated region (UTR) of TLR4 was associated with periodontitis. In this
      study the effects of this single nucleotide polymorphism on Toll-like receptor
      (TLR) 4 expression were investigated. Monocytes from subjects with the C/C
      genotype expressed higher levels of TLR4 on their surfaces than those from
      subjects with the other genotypes. Peripheral blood mononuclear cells (PBMCs)
      from the C/C and G/C subjects secreted higher levels of IL-8 in response to
      lipopolysaccharide (LPS), a TLR4 ligand, than the cells from the G/G subjects.
      However, there was no significant difference in TLR4 mRNA levels in PBMCs from
      the subjects with each genotype. After stimulation with tripalmitoylated CSK(4)
      (Pam(3)CSK(4)), TLR4 mRNA levels increased in PBMCs from both the C/C and G/G
      subjects, whereas TLR4 protein levels increased in PBMCs from the C/C but not G/G
      subjects. Transient transfection of a series of chimeric luciferase constructs
      revealed that a fragment of 3'-UTR containing rs11536889 G allele, but not C
      allele, suppressed luciferase activity induced by LPS or IL-6. Two microRNAs, hsa
      miR-1236 and hsa-miR-642a, were predicted to bind to rs11536889 G allele.
      Inhibition of these microRNAs reversed the suppressed luciferase activity. These
      microRNA inhibitors also up-regulated endogenous TLR4 protein on THP-1 cells (the
      G/G genotype) after LPS stimulation. Furthermore, mutant microRNAs that bind to
      the C allele inhibited the luciferase activity of the construct containing the C
      allele. These results indicate that genetic variation of rs11536889 contributes
      to translational regulation of TLR4, possibly by binding to microRNAs.

PMID- 22661709
TI  - Intra- and interprotein phosphorylation between two-hybrid histidine kinases
      controls Myxococcus xanthus developmental progression.
AB  - Histidine-aspartate phosphorelay signaling systems are used to couple stimuli to
      cellular responses. A hallmark feature is the highly modular signal transmission
      modules that can form both simple "two-component" systems and sophisticated
      multicomponent systems that integrate stimuli over time and space to generate
      coordinated and fine-tuned responses. The deltaproteobacterium Myxococcus xanthus
      contains a large repertoire of signaling proteins, many of which regulate its
      multicellular developmental program. Here, we assign an orphan hybrid histidine
      protein kinase, EspC, to the Esp signaling system that negatively regulates
      progression through the M. xanthus developmental program. The Esp signal system
      consists of the hybrid histidine protein kinase, EspA, two serine/threonine
      protein kinases, and a putative transport protein. We demonstrate that EspC is an
      essential component of this system because DeltaespA, DeltaespC, and DeltaespA
      DeltaespC double mutants share an identical developmental phenotype. Neither
      substitution of the phosphoaccepting histidine residue nor deletion of the entire
      catalytic ATPase domain in EspC produces an in vivo mutant developmental
      phenotype. In contrast, substitution of the receiver phosphoaccepting residue
      yields the null phenotype. Although the EspC histidine kinase can efficiently
      autophosphorylate in vitro, it does not act as a phosphodonor to its own receiver
      domain. Our in vitro and in vivo analyses suggest the phosphodonor is instead the
      EspA histidine kinase. We propose EspA and EspC participate in a novel hybrid
      histidine protein kinase signaling mechanism involving both inter- and
      intraprotein phosphotransfer. The output of this signaling system appears to be
      the combined phosphorylated state of the EspA and EspC receiver modules. This
      system regulates the proteolytic turnover of MrpC, an important regulator of the
      developmental program.

PMID- 22661710
TI  - Paralogous outer membrane proteins mediate uptake of different forms of iron and
      synergistically govern virulence in Francisella tularensis tularensis.
AB  - Francisella tularensis subsp. tularensis is a highly infectious bacterium causing
      acute disease in mammalian hosts. Mechanisms for the acquisition of iron within
      the iron-limiting host environment are likely to be critical for survival of this
      intracellular pathogen. FslE (FTT0025) and FupA (FTT0918) are paralogous proteins
      that are predicted to form beta-barrels in the outer membrane of virulent strain
      Schu S4 and are unique to Francisella species. Previous studies have implicated
      both FupA, initially identified as a virulence factor and FslE, encoded by the
      siderophore biosynthetic operon, in iron acquisition. Using single and double
      mutants, we demonstrated that these paralogs function in concert to promote
      growth under iron limitation. We used a (55)Fe transport assay to demonstrate
      that FslE is involved in siderophore-mediated ferric iron uptake, whereas FupA
      facilitates high affinity ferrous iron uptake. Optimal replication within J774A.1
      macrophage-like cells required at least one of these uptake systems to be
      functional. In a mouse model of tularemia, the DeltafupA mutant was attenuated,
      but the DeltafslE DeltafupA mutant was significantly more attenuated, implying
      that the two systems of iron acquisition function synergistically to promote
      virulence. These studies highlight the importance of specific iron acquisition
      functions, particularly that of ferrous iron, for virulence of F. tularensis in
      the mammalian host.

PMID- 22661711
TI  - Retinoic acid receptors recognize the mouse genome through binding elements with
      diverse spacing and topology.
AB  - Retinoic acid receptors (RARs) heterodimerize with retinoid X receptors (RXRs)
      and bind to RA response elements (RAREs) in the regulatory regions of their
      target genes. Although previous studies on limited sets of RA-regulated genes
      have defined canonical RAREs as direct repeats of the consensus RGKTCA separated
      by 1, 2, or 5 nucleotides (DR1, DR2, DR5), we show that in mouse embryoid bodies
      or F9 embryonal carcinoma cells, RARs occupy a large repertoire of sites with
      DR0, DR8, and IR0 (inverted repeat 0) elements. Recombinant RAR-RXR binds these
      non-canonical spacings in vitro with comparable affinities to DR2 and DR5. Most
      DR8 elements comprise three half-sites with DR2 and DR0 spacings. This specific
      half-site organization constitutes a previously unrecognized but frequent
      signature of RAR binding elements. In functional assays, DR8 and IR0 elements act
      as independent RAREs, whereas DR0 does not. Our results reveal an unexpected
      diversity in the spacing and topology of binding elements for the RAR-RXR
      heterodimer. The differential ability of RAR-RXR bound to DR0 compared to DR2,
      DR5, and DR8 to mediate RA-dependent transcriptional activation indicates that
      half-site spacing allosterically regulates RAR function.

PMID- 22661712
TI  - Crystal structure of human ADP-ribose transferase ARTD15/PARP16 reveals a novel
      putative regulatory domain.
AB  - ADP-ribosylation is involved in the regulation of DNA repair, transcription, and
      other processes. The 18 human ADP-ribose transferases with diphtheria toxin
      homology include ARTD1/PARP1, a cancer drug target. Knowledge of other family
      members may guide therapeutics development and help evaluate potential drug side
      effects. Here, we present the crystal structure of human ARTD15/PARP16, a
      previously uncharacterized enzyme. ARTD15 features an alpha-helical domain that
      packs against its transferase domain without making direct contact with the
      NAD(+)-binding crevice or the donor loop. Thus, this novel domain does not
      resemble the regulatory domain of ARTD1. ARTD15 displays auto-mono(ADP
      ribosylation) activity and is affected by canonical poly(ADP-ribose) polymerase
      inhibitors. These results add to a framework that will facilitate research on a
      medically important family of enzymes.

PMID- 22661713
TI  - Oxidative stress induced S-glutathionylation and proteolytic degradation of
      mitochondrial thymidine kinase 2.
AB  - Protein glutathionylation in response to oxidative stress can affect both the
      stability and activity of target proteins. Mitochondrial thymidine kinase 2 (TK2)
      is a key enzyme in mitochondrial DNA precursor synthesis. Using an antibody
      specific for glutathione (GSH), S-glutathionylated TK2 was detected after the
      addition of glutathione disulfide (GSSG) but not GSH. This was reversed by the
      addition of dithiothreitol, suggesting that S-glutathionylation of TK2 is
      reversible. Site-directed mutagenesis of the cysteine residues and subsequent
      analysis of mutant enzymes demonstrated that Cys-189 and Cys-264 were
      specifically glutathionylated by GSSG. These cysteine residues do not appear to
      be part of the active site, as demonstrated by kinetic studies of the mutant
      enzymes. Treatment of isolated rat mitochondria with hydrogen peroxide resulted
      in S-glutathionylation of added recombinant TK2. Treatment of intact cells with
      hydrogen peroxide led to reduction of mitochondrial TK2 activity and protein
      levels, as well as S-glutathionylation of TK2. Furthermore, the addition of S
      glutathionylated recombinant TK2 to mitochondria isolated from hydrogen peroxide
      treated cells led to degradation of the S-glutathionylated TK2, which was not
      observed with unmodified TK2. S-Glutathionylation on Cys-189 was responsible for
      the observed selective degradation of TK2 in mitochondria. These results strongly
      suggest that oxidative damage-induced S-glutathionylation and degradation of TK2
      have significant impact on mitochondrial DNA precursor synthesis.

PMID- 22661714
TI  - A novel fluorescent cell membrane-permeable caged cyclic ADP-ribose analogue.
AB  - Cyclic adenosine diphosphate ribose is an endogenous Ca(2+) mobilizer involved in
      diverse cellular processes. A cell membrane-permeable cyclic adenosine
      diphosphate ribose analogue, cyclic inosine diphosphoribose ether (cIDPRE), can
      induce Ca(2+) increase in intact human Jurkat T-lymphocytes. Here we synthesized
      a coumarin-caged analogue of cIDPRE (Co-i-cIDPRE), aiming to have a precisely
      temporal and spatial control of bioactive cIDPRE release inside the cell using UV
      uncaging. We showed that Co-i-cIDPRE accumulated inside Jurkat cells quickly and
      efficiently. Uncaging of Co-i-cIDPRE evoked Ca(2+) release from endoplasmic
      reticulum, with concomitant Ca(2+) influx in Jurkat cells. Ca(2+) release evoked
      by uncaged Co-i-cIDPRE was blocked by knockdown of ryanodine receptors (RyRs) 2
      and 3 in Jurkat cells. The associated Ca(2+) influx, on the other hand, was
      abolished by double knockdown of Stim1 and TRPM2 in Jurkat cells. Furthermore,
      Ca(2+) release or influx evoked by uncaged Co-i-cIDPRE was recapitulated in
      HEK293 cells that overexpress RyRs or TRPM2, respectively, but not in wild-type
      cells lacking these channels. In summary, our results indicate that uncaging of
      Co-i-cIDPRE incites Ca(2+) release from endoplasmic reticulum via RyRs and
      triggers Ca(2+) influx via TRPM2.

PMID- 22661715
TI  - Trypanosoma brucei 20 S editosomes have one RNA substrate-binding site and
      execute RNA unwinding activity.
AB  - Editing of mitochondrial pre-mRNAs in African trypanosomes generates full-length
      transcripts by the site-specific insertion and deletion of uridylate nucleotides.
      The reaction is catalyzed by a 0.8 MDa multienzyme complex, the editosome.
      Although the binding of substrate pre-edited mRNAs and cognate guide RNAs (gRNAs)
      represents the first step in the reaction cycle, the biochemical and biophysical
      details of the editosome/RNA interaction are not understood. Here we show that
      editosomes bind full-length substrate mRNAs with nanomolar affinity in a
      nonselective fashion. The complexes do not discriminate-neither kinetically nor
      thermodynamically-between different mitochondrial pre-mRNAs or between edited and
      unedited versions of the same transcript. They also bind gRNAs and gRNA/pre-mRNA
      hybrid RNAs with similar affinities and association rate constants. Gold labeling
      of editosome-bound RNA in combination with transmission electron microscopy
      identified a single RNA-binding site per editosome. However, atomic force
      microscopy of individual pre-mRNA-editosome complexes revealed that multiple
      editosomes can interact with one pre-mRNA. Lastly, we demonstrate a so far
      unknown activity of the editing machinery: editosome-bound RNA becomes unfolded
      by a chaperone-type RNA unwinding activity.

PMID- 22661716
TI  - Activation of p115-RhoGEF requires direct association of Galpha13 and the Dbl
      homology domain.
AB  - RGS-containing RhoGEFs (RGS-RhoGEFs) represent a direct link between the G(12)
      class of heterotrimeric G proteins and the monomeric GTPases. In addition to the
      canonical Dbl homology (DH) and pleckstrin homology domains that carry out the
      guanine nucleotide exchange factor (GEF) activity toward RhoA, these RhoGEFs also
      possess RGS homology (RH) domains that interact with activated alpha subunits of
      G(12) and G(13). Although the GEF activity of p115-RhoGEF (p115), an RGS-RhoGEF,
      can be stimulated by Galpha(13), the exact mechanism of the stimulation has
      remained unclear. Using combined studies with small angle x-ray scattering,
      biochemistry, and mutagenesis, we identify an additional binding site for
      activated Galpha(13) in the DH domain of p115. Small angle x-ray scattering
      reveals that the helical domain of Galpha(13) docks onto the DH domain, opposite
      to the surface of DH that binds RhoA. Mutation of a single tryptophan residue in
      the alpha3b helix of DH reduces binding to activated Galpha(13) and ablates the
      stimulation of p115 by Galpha(13). Complementary mutations at the predicted DH
      binding site in the alphaB-alphaC loop of the helical domain of Galpha(13) also
      affect stimulation of p115 by Galpha(13). Although the GAP activity of p115 is
      not required for stimulation by Galpha(13), two hydrophobic motifs in RH outside
      of the consensus RGS box are critical for this process. Therefore, the binding of
      Galpha(13) to the RH domain facilitates direct association of Galpha(13) to the
      DH domain to regulate its exchange activity. This study provides new insight into
      the mechanism of regulation of the RGS-RhoGEF and broadens our understanding of G
      protein signaling.

PMID- 22661717
TI  - Activation of the farnesoid X receptor induces hepatic expression and secretion
      of fibroblast growth factor 21.
AB  - Previous studies have shown that starvation or consumption of a high fat, low
      carbohydrate (HF-LC) ketogenic diet induces hepatic fibroblast growth factor 21
      (FGF21) gene expression in part by activating the peroxisome proliferator
      activated receptor-alpha (PPARalpha). Using primary hepatocyte cultures to screen
      for endogenous signals that mediate the nutritional regulation of FGF21
      expression, we identified two sources of PPARalpha activators (i.e. nonesterified
      unsaturated fatty acids and chylomicron remnants) that induced FGF21 gene
      expression. In addition, we discovered that natural (i.e. bile acids) and
      synthetic (i.e. GW4064) activators of the farnesoid X receptor (FXR) increased
      FGF21 gene expression and secretion. The effects of bile acids were additive with
      the effects of nonesterified unsaturated fatty acids in regulating FGF21
      expression. FXR activation of FGF21 gene transcription was mediated by an
      FXR/retinoid X receptor binding site in the 5'-flanking region of the FGF21 gene.
      FGF19, a gut hormone whose expression and secretion is induced by intestinal bile
      acids, also increased hepatic FGF21 secretion. Deletion of FXR in mice suppressed
      the ability of an HF-LC ketogenic diet to induce hepatic FGF21 gene expression.
      The results of this study identify FXR as a new signaling pathway activating
      FGF21 expression and provide evidence that FXR activators work in combination
      with PPARalpha activators to mediate the stimulatory effect of an HF-LC ketogenic
      diet on FGF21 expression. We propose that the enhanced enterohepatic flux of bile
      acids during HF-LC consumption leads to activation of hepatic FXR and FGF19
      signaling activity and an increase in FGF21 gene expression and secretion.

PMID- 22661718
TI  - Characterization and solution structure of mouse myristoylated methionine
      sulfoxide reductase A.
AB  - Methionine sulfoxide reductase A is an essential enzyme in the antioxidant system
      which scavenges reactive oxygen species through cyclic oxidation and reduction of
      methionine and methionine sulfoxide. The cytosolic form of the enzyme is
      myristoylated, but it is not known to translocate to membranes, and the function
      of myristoylation is not established. We compared the biochemical and biophysical
      properties of myristoylated and nonmyristoylated mouse methionine sulfoxide
      reductase A. These were almost identical for both forms of the enzyme, except
      that the myristoylated form reduced methionine sulfoxide in protein much faster
      than the nonmyristoylated form. We determined the solution structure of the
      myristoylated protein and found that the myristoyl group lies in a relatively
      surface exposed "myristoyl nest." We propose that this structure functions to
      enhance protein-protein interaction.

PMID- 22661719
TI  - A low pKa cysteine at the active site of mouse methionine sulfoxide reductase A.
AB  - Methionine sulfoxide reductase A is an essential enzyme in the antioxidant system
      which scavenges reactive oxygen species through cyclic oxidation and reduction of
      methionine and methionine sulfoxide. Recently it has also been shown to catalyze
      the reverse reaction, oxidizing methionine residues to methionine sulfoxide. A
      cysteine at the active site of the enzyme is essential for both reductase and
      oxidase activities. This cysteine has been reported to have a pK(a) of 9.5 in the
      absence of substrate, decreasing to 5.7 upon binding of substrate. Using three
      independent methods, we show that the pK(a) of the active site cysteine of mouse
      methionine sulfoxide reductase is 7.2 even in the absence of substrate. The
      primary mechanism by which the pK(a) is lowered is hydrogen bonding of the active
      site Cys-72 to protonated Glu-115. The low pK(a) renders the active site cysteine
      susceptible to oxidation to sulfenic acid by micromolar concentrations of
      hydrogen peroxide. This characteristic supports a role for methionine sulfoxide
      reductase in redox signaling.

PMID- 22661721
TI  - A farmer with fever and right upper quadrant pain.

PMID- 22661722
TI  - 15 Minute consultations as standard benefit patients and GPs.

PMID- 22661720
TI  - The C-terminal domain of 4-hydroxyphenylacetate 3-hydroxylase from Acinetobacter
      baumannii is an autoinhibitory domain.
AB  - p-Hydroxyphenylacetate (HPA) 3-hydroxylase from Acinetobacter baumannii consists
      of a reductase component (C(1)) and an oxygenase component (C(2)). C(1) catalyzes
      the reduction of FMN by NADH to provide FMNH(-) as a substrate for C(2). The rate
      of reduction of flavin is enhanced ~20-fold by binding HPA. The N-terminal domain
      of C(1) is homologous to other flavin reductases, whereas the C-terminal domain
      (residues 192-315) is similar to MarR, a repressor protein involved in bacterial
      antibiotic resistance. In this study, three forms of truncated C(1) variants and
      single site mutation variants of residues Arg-21, Phe-216, Arg-217, Ile-246, and
      Arg-247 were constructed to investigate the role of the C-terminal domain in
      regulating C(1). In the absence of HPA, the C(1) variant in which residues 179
      315 were removed (t178C(1)) was reduced by NADH and released FMNH(-) at the same
      rates as wild-type enzyme carries out these functions in the presence of HPA. In
      contrast, variants with residues 231-315 removed behaved similarly to the wild
      type enzyme. Thus, residues 179-230 are involved in repressing the production of
      FMNH(-) in the absence of HPA. These results are consistent with the C-terminal
      domain in the wild-type enzyme being an autoinhibitory domain that upon binding
      the effector HPA undergoes conformational changes to allow faster flavin
      reduction and release. Most of the single site variants investigated had
      catalytic properties similar to those of the wild-type enzyme except for the
      F216A variant, which had a rate of reduction that was not stimulated by HPA.
      F216A could be involved with HPA binding or in the required conformational change
      for stimulation of flavin reduction by HPA.

PMID- 22661723
TI  - Feature did not explore how consultancies and government should interact.

PMID- 22661724
TI  - Novo Nordisk's reply to call for withdrawal of liraglutide.

PMID- 22661725
TI  - Bridging the gap: an integrated paediatric to adult clinical service for young
      adults with kidney failure.
AB  - PROBLEM: Transition from paediatric to adult care of young adults with chronic
      diseases is poorly coordinated, often delayed, and usually managed through a
      single referral letter. About 35% of young adults lose a successfully functioning
      kidney transplant within 36 months of transfer from paediatric to adult services.
      DESIGN: Before and after study of the impact of a new integrated paediatric-adult
      clinical service for patients with kidney failure. SETTING: Adult renal centre in
      Oxford and two paediatric renal centres in London. STRATEGIES FOR CHANGE: An
      integrated paediatric-young adult joint transition clinic and care pathway was
      established in 2006, in conjunction with a young adult clinical service with
      regular community based clinics. Previously, young adult transplant recipients
      were transferred by a single referral letter to an adult renal consultant and
      managed in a conventional adult clinic. KEY MEASURES FOR IMPROVEMENT: Rates of
      acute rejection and loss of kidney transplants five years before and five years
      after the introduction of the integrated young adult care pathway.  EFFECTS OF
      THE CHANGE:   Nine young adult kidney transplant recipients were transferred
      directly to adult care between 2000 and 2006 (group 1). From 2006 to 2010, 12
      young adult transplant recipients underwent integrated transition into the new
      young adult service (group 2). Six transplants were lost in group 1 (67%)
      compared with no transplant losses in group 2. LESSONS LEARNT: Implementing an
      integrated transition clinic, coupled with improving young adults' healthcare
      experience through a young adult clinic, improved patient adherence to regular
      medication and engagement with healthcare providers, as judged by reduced
      transplant failure rates. This model may be applicable to other young adult
      populations with chronic disease transferring to adult healthcare.

PMID- 22661726
TI  - Plastic food packaging encourages obesity.

PMID- 22661727
TI  - Make the healthy choice the cheaper choice.

PMID- 22661728
TI  - Canadian doctors try to garner public support to fight pay freeze.

PMID- 22661729
TI  - Low sodium diets can be both nutritious and low cost.

PMID- 22661730
TI  - Beware renal adverse effects of anti-vascular endothelial growth factor
      treatment.

PMID- 22661731
TI  - Flawed analysis may be used to restrict birth choices.

PMID- 22661732
TI  - Histological analysis of all scalp cysts is counsel of perfection.

PMID- 22661735
TI  - Another doctor does investigate all hospital deaths.

PMID- 22661736
TI  - Judge orders Spanish doctor to pay for child support after a failed abortion.

PMID- 22661737
TI  - Where specialist diabetes teams can be found.

PMID- 22661738
TI  - Bad medicine: dementia.

PMID- 22661739
TI  - League was based on consumer survey sponsored by drug industry.

PMID- 22661740
TI  - Vaccinating healthy children against flu is cost effective, says committee.

PMID- 22661741
TI  - Senator questions $2m NIH grant to disgraced psychiatric researcher.

PMID- 22661742
TI  - Pathologist complains to BBC and Ofcom about her portrayal in television drama.

PMID- 22661743
TI  - Ban on recreational drugs is impeding science, says former government drugs
      adviser.

PMID- 22661744
TI  - Self-reported cocaine use, emergency physician testing and outcomes in suspected
      acute coronary syndromes: a nested matched case-control study.
AB  - OBJECTIVES: The primary purpose was to compare the odds of acute coronary
      syndrome-pertinent diagnostic testing between self-reported cocaine users and non
      users at the turn of the century. The secondary purpose was to compare the odds
      of acute coronary syndrome outcomes between cocaine users and non-users. DESIGN:
      Nested matched case-control study using data from the Internet Tracking Registry
      of Acute Coronary Syndromes. SETTING: Extracted data of patients from eight US
      institutions composed of six academic and two community hospitals, with census
      varying between 10 000 and 160 000 visits per year. PARTICIPANTS: 249 cases of
      self-reported cocaine users and 249 matched controls. Matching was based on age,
      race, sex and any history of known coronary artery disease. Exclusion criteria
      were new ST elevations on initial ECG and initial physician impression of acute
      myocardial infarction. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome
      was the conditional odds of undergoing non-invasive and invasive testing for
      coronary artery disease. Secondary outcome was the occurrences of adverse cardiac
      outcomes within 30 days. RESULTS: Cocaine users underwent diagnostic testing at
      similar rates compared with non-users (9.6% vs 8.0%, OR 1.24, CI 0.65 to 2.34).
      Adverse cardiovascular outcomes occurred in four (1.6%) cocaine users and in
      seven (2.8%) controls. CONCLUSIONS: There was no increase in tendency for testing
      associated with self-reported history of cocaine use between 1999 and 2001. This
      suggests that even 10 years ago, cocaine use already had only a limited role in
      the Emergency Department (ED) physician's decision-making process. Similar data
      analyses of detailed registries can offer important contextual information that
      can better direct resources for future comparative effectiveness research.

PMID- 22661745
TI  - Impact of Chinese one-child policy on sibling structure: experience from rural
      areas in three provinces.
AB  - OBJECTIVES: To study the influence of population policy and boy preference on the
      sibling structure, that is, in which order and combinations boys and girls are
      born into families. DESIGN: A population-based survey with a representative
      sample of new mothers in 2008-2009 in rural China. SETTING: Two provinces (Anhui
      and Shaanxi) where authorisation for a second child was usually given if the
      first birth was a daughter and one province (Chongqing) where only one child was
      authorised. PARTICIPANTS: The mothers giving birth in 2008-2009 were identified
      from family planning and hospital birth registers (including births outside
      hospitals) (n=5049). Of them, 3673 were interviewed by trained medical university
      staff members and students using structured questionnaire (response rate 73%).
      MAIN OUTCOME MEASURES: Children's distribution by sex and families' distribution
      by children's birth order and sex composition were calculated and compared with
      theoretical values based on the assumption that family planning policy is fully
      followed. RESULTS: The recommended family policy was varyingly followed in the
      three provinces. In all provinces, there were more second children than allowed.
      If the policy allowing a second child only after a first-born girl were fully
      followed, it would result in a sibling structure in which the one-child family is
      always with a boy and in the two-child family the first one is always a girl.
      This sibling structure was partly seen in Anhui but weakly in Shaanxi. The policy
      allowing only one child would result in an equal number of boys and girls, but in
      Chongqing, there were more boys. In Anhui, unlike the other provinces, there were
      many more first-born girls than boys, which the authors could not fully explain.
      CONCLUSION: Population policy and boy preference influence the actual and
      relative number of girls and boys and also sibling structure.

PMID- 22661746
TI  - Young-onset amyotrophic lateral sclerosis: historical and other observations.
AB  - There is a wide range of age at initial symptom onset in amyotrophic lateral
      sclerosis despite a mean age of 65 years in population-based studies. 'Young
      onset' amyotrophic lateral sclerosis typically refers to patients younger than
      ~45 years and accounts for about 10% of cases in contemporary series. A review of
      published cases of amyotrophic lateral sclerosis from 1850 to 1950 revealed a far
      higher proportion of cases with young onset (>50%), with a steady decline to the
      contemporary figure. It is possible that this is not solely explained by
      increases in life expectancy. While there is still a rich variation in phenotypes
      among cases of young-onset amyotrophic lateral sclerosis, bulbar onset was found
      to be significantly under-represented in analysis of a large patient database,
      with implications for age-related vulnerabilities pertaining to focality of
      symptom onset. The timing of initiating pathological processes in relation to the
      emergence of symptoms is discussed, including the potential role of very early
      development and the interaction of epigenetic and environmental factors.

PMID- 22661747
TI  - Intraoperative fluids: how much is too much?
AB  - There is increasing evidence that intraoperative fluid therapy decisions may
      influence postoperative outcomes. In the past, patients undergoing major surgery
      were often administered large volumes of crystalloid, based on a presumption of
      preoperative dehydration and nebulous intraoperative 'third space' fluid loss.
      However, positive perioperative fluid balance, with postoperative fluid-based
      weight gain, is associated with increased major morbidity. The concept of 'third
      space' fluid loss has been emphatically refuted, and preoperative dehydration has
      been almost eliminated by reduced fasting times and use of oral fluids up to 2 h
      before operation. A 'restrictive' intraoperative fluid regimen, avoiding
      hypovolaemia but limiting infusion to the minimum necessary, initially reduced
      major complications after complex surgery, but inconsistencies in defining
      restrictive vs liberal fluid regimens, the type of fluid infused, and in
      definitions of adverse outcomes have produced conflicting results in clinical
      trials. The advent of individualized goal-directed fluid therapy, facilitated by
      minimally invasive, flow-based cardiovascular monitoring, for example,
      oesophageal Doppler monitoring, has improved outcomes in colorectal surgery in
      particular, and this monitor has been approved by clinical guidance authorities.
      In the contrasting clinical context of relatively low-risk patients undergoing
      ambulatory surgery, high-volume crystalloid infusion (20-30 ml kg(-1)) reduces
      postoperative nausea and vomiting, dizziness, and pain. This review revises
      relevant physiology of body water distribution and capillary-tissue flow
      dynamics, outlines the rationale behind the fluid regimens mentioned above, and
      summarizes the current clinical evidence base for them, particularly the
      increasing use of individualized goal-directed fluid therapy facilitated by
      oesophageal Doppler monitoring.

PMID- 22661748
TI  - Risks for impaired cerebral autoregulation during cardiopulmonary bypass and
      postoperative stroke.
AB  - BACKGROUND: Impaired cerebral autoregulation may predispose patients to cerebral
      hypoperfusion during cardiopulmonary bypass (CPB). The purpose of this study was
      to identify risk factors for impaired autoregulation during coronary artery
      bypass graft, valve surgery with CPB, or both and to evaluate whether near
      infrared spectroscopy (NIRS) autoregulation monitoring could be used to identify
      this condition. METHODS: Two hundred and thirty-four patients were monitored with
      transcranial Doppler and NIRS. A continuous, moving Pearson's correlation
      coefficient was calculated between mean arterial pressure (MAP) and cerebral
      blood flow (CBF) velocity, and between MAP and NIRS data, to generate the mean
      velocity index (Mx) and cerebral oximetry index (COx), respectively. Functional
      autoregulation is indicated by an Mx and COx that approach zero (no correlation
      between CBF and MAP); impaired autoregulation is indicated by an Mx and COx
      approaching 1. Impaired autoregulation was defined as an Mx >=0.40 at all MAPs
      during CPB. RESULTS: Twenty per cent of patients demonstrated impaired
      autoregulation during CPB. Based on multivariate logistic regression analysis,
      time-averaged COx during CPB, male gender, Pa(CO(2)), CBF velocity, and
      preoperative aspirin use were independently associated with impaired CBF
      autoregulation. Perioperative stroke occurred in six of 47 (12.8%) patients with
      impaired autoregulation compared with five of 187 (2.7%) patients with preserved
      autoregulation (P=0.011). CONCLUSIONS: Impaired CBF autoregulation occurs in 20%
      of patients during CPB. Patients with impaired autoregulation are more likely
      than those with functional autoregulation to have perioperative stroke. Non
      invasive monitoring autoregulation may provide an accurate means to predict
      impaired autoregulation. Clinical trials registration. www.clinicaltrials.gov
      (NCT00769691).

PMID- 22661749
TI  - Using quality indicators in anaesthesia: feeding back data to improve care.
AB  - After recent UK policy developments, considerable attention has been focused upon
      how clinical specialties measure and report on the quality of care delivered to
      patients. Defining the right indicators alone is insufficient to close the
      feedback loop. This narrative review aims to describe and synthesize a diverse
      body of research relevant to the question of how information from quality
      indicators can be fed back and used effectively to improve care. Anaesthesia
      poses certain challenges in the identification of valid outcome indicators
      sensitive to variations in anaesthetic care. Metrics collected during the
      immediate post-anaesthetic recovery period, such as patient temperature, patient
      reported quality of recovery, and pain and nausea, provide potentially useful
      information for the anaesthetist, yet this information is not routinely fed back.
      Reviews of the effects of feeding back performance data to healthcare providers
      suggest that this may result in small to moderate positive effects upon outcomes
      and professional practice, with stronger effects where feedback is integrated
      within a broader quality improvement strategy. The dominant model for use of data
      within quality improvement is based upon the industrial process control approach,
      in which care processes are monitored continuously for process changes which are
      rapidly detectable for corrective action. From this review and experience of
      implementing these principles in practice, effective feedback from quality
      indicators is timely, credible, confidential, tailored to the recipient, and
      continuous. Considerable further work is needed to understand how information
      from quality indicators can be fed back in an effective way to clinicians and
      clinical units, in order to support revalidation and continuous improvement.

PMID- 22661750
TI  - Ventilation with low tidal volumes during upper abdominal surgery does not
      improve postoperative lung function.
AB  - BACKGROUND: Prolonged postoperative decrease in lung function is common after
      major upper abdominal surgery. Evidence suggests that ventilation with low tidal
      volumes may limit the damage during mechanical ventilation. We compared
      postoperative lung function of patients undergoing upper abdominal surgery,
      mechanically ventilated with high or low tidal volumes. METHODS: This was a
      double-blind, prospective, randomized controlled clinical trial. One hundred and
      one patients (age >= 50 yr, ASA >= II, duration of surgery >= 3 h) were
      ventilated with: (i) high [12 ml kg(-1) predicted body weight (PBW)] or (ii) low
      (6 ml kg(-1) PBW) tidal volumes intraoperatively. The positive end-expiratory
      pressure was 5 cm H(2)O in both groups and breathing frequency adjusted to
      normocapnia. Time-weighted averages (TWAs) of forced vital capacity (FVC) and
      forced expiratory volume in 1 s (FEV(1)) until 120 h after operation were
      compared (P<0.025 considered statistically significant). Secondary outcomes were
      oxygenation, respiratory and non-respiratory complications, length of stay and
      mortality. RESULTS: The mean (sd) values of TWAs of FVC and FEV(1) were similar
      in both groups: FVC: 6 ml group 1.8 (0.7) litre vs 12 ml group 1.6 (0.5) litre
      (P=0.12); FEV(1): 6 ml group 1.4 (0.5) litre vs 12 ml group 1.2 (0.4) litre
      (P=0.15). FVC and FEV(1) at any single time point and secondary outcomes did not
      differ significantly between groups. CONCLUSIONS: Prolonged impaired lung
      function after major abdominal surgery is not ameliorated by low tidal volume
      ventilation.

PMID- 22661751
TI  - Cadaver study of oesophageal insufflation with supraglottic airway devices during
      positive pressure ventilation in an obstructed airway.
AB  - BACKGROUND: Supraglottic airway devices (SADs) play an increasing role in airway
      management in clinical anaesthesia and emergency medicine. Until now, no data
      exist concerning the extent of oesophageal insufflation when oropharyngeal leak
      pressures are exceeded. METHODS: Laryngeal masks LMA-SupremeTM and LMA-ProSealTM,
      laryngeal tubes LTS-D and LTS II, CombitubeTM, and I-Gel were inserted into
      unfixed human cadavers. The oesophagus was connected to a volumeter, while the
      trachea was closed surgically to simulate complete airway obstruction. Volumes of
      oesophageal insufflation resulting from pressure-controlled ventilation at
      inspiratory pressures of 20, 40, and 60 mbar were measured. RESULTS: No
      oesophageal insufflation could be detected at a ventilation pressure of 20 mbar
      in any device. Using inspiratory pressures of 40 and 60 mbar, oesophageal
      insufflation occurred in all devices, with significantly higher volumes of
      intraoesophageal air for both laryngeal tubes. CONCLUSIONS: The use of SADs with
      inspiratory pressures of 20 mbar appears to be safe regarding the risk of
      intragastric insufflation. Higher inspiratory pressures should be strictly
      avoided.

PMID- 22661752
TI  - Changes in cerebrospinal fluid magnesium levels in patients undergoing spinal
      anaesthesia for hip arthroplasty: does intravenous infusion of magnesium sulphate
      make any difference? A prospective, randomized, controlled study.
AB  - BACKGROUND: Most investigators have attributed the reduced postoperative pain or
      anaesthetic drug requirements in patients receiving i.v. magnesium sulphate
      (MgSO(4)) infusion during spinal or general anaesthesia to central N-methyl-d
      aspartate (NMDA) receptor magnesium (Mg) activity. In this study, we investigated
      how cerebrospinal fluid (CSF) Mg concentrations change after spinal anaesthesia,
      and whether peripherally infusing MgSO(4) influences central Mg levels. METHODS:
      Forty-five patients undergoing continuous spinal anaesthesia for hip arthroplasty
      were randomly assigned to receive either i.v. MgSO(4) at a dose of 50 mg kg(-1)
      diluted in 100 ml 0.9% saline solution followed by 15 mg kg(-1) h(-1) for 6 h or
      saline at the same volume [mean (sd) 64 (10) ml]. The changes in CSF and serum
      total and ionized Mg concentrations were assessed at six time points before and
      after spinal anaesthesia. Secondary outcome variables included serum and CSF
      electrolytes and proteins. RESULTS: Thirty-five patients completed the study. We
      found that spinal anaesthesia reduced total and ionized Mg concentrations in CSF
      by about 10%. Increasing serum Mg concentration over 80% of the baseline value
      left CSF Mg levels unchanged. CONCLUSIONS: Spinal anaesthesia unexpectedly
      reduced CSF total and ionized Mg concentrations in patients undergoing hip
      arthroplasty, although the mechanism is unclear. The dose used for peripheral
      MgSO(4) infusion in this study had no influence on central Mg concentrations in
      neurologically healthy patients undergoing spinal anaesthesia. If CSF Mg
      concentration is a reliable marker of Mg brain bioavailability, peripherally
      infused MgSO(4) during spinal anaesthesia is unlikely to influence central NMDA
      receptor activity.

PMID- 22661755
TI  - The mission of StaR Child Health is to improve the quality of the design,
      conduct, and reporting of pediatric clinical research by promoting the use of
      modern research standards. Introduction.

PMID- 22661756
TI  - StaR child health: developing evidence-based guidance for the design, conduct,
      and reporting of pediatric trials.

PMID- 22661757
TI  - Standard 1: consent and recruitment.

PMID- 22661758
TI  - Standard 2: containing risk of bias.

PMID- 22661759
TI  - Standard 3: data monitoring committees.

PMID- 22661760
TI  - Standard 4: determining adequate sample sizes.

PMID- 22661761
TI  - Standard 5: selection, measurement, and reporting of outcomes in clinical trials
      in children.

PMID- 22661762
TI  - Standard 6: age groups for pediatric trials.

PMID- 22661763
TI  - Empirical evaluation of age groups and age-subgroup analyses in pediatric
      randomized trials and pediatric meta-analyses.
AB  - BACKGROUND: An important step toward improvement of the conduct of pediatric
      clinical research is the standardization of the ages of children to be included
      in pediatric trials and the optimal age-subgroups to be analyzed. METHODS: We set
      out to evaluate empirically the age ranges of children, and age-subgroup analyses
      thereof, reported in recent pediatric randomized clinical trials (RCTs) and meta
      analyses. First, we screened 24 RCTs published in Pediatrics during the first 6
      months of 2011; second, we screened 188 pediatric RCTs published in 2007 in the
      Cochrane Central Register of Controlled Trials; third, we screened 48 pediatric
      meta-analyses published in the Cochrane Database of Systematic Reviews in 2011.
      We extracted information on age ranges and age-subgroups considered and age
      subgroup differences reported. RESULTS: The age range of children in RCTs
      published in Pediatrics varied from 0.1 to 17.5 years (median age: 5;
      interquartile range: 1.8-10.2) and only 25% of those presented age-subgroup
      analyses. Large variability was also detected for age ranges in 188 RCTs from the
      Cochrane Central Register of Controlled Trials, and only 28 of those analyzed age
      subgroups. Moreover, only 11 of 48 meta-analyses had age-subgroup analyses, and
      in 6 of those, only different studies were included. Furthermore, most of these
      observed differences were not beyond chance. CONCLUSIONS: We observed large
      variability in the age ranges and age-subgroups of children included in recent
      pediatric trials and meta-analyses. Despite the limited available data, some age
      subgroup differences were noted. The rationale for the selection of particular
      age-subgroups deserves further study.

PMID- 22661765
TI  - Liver autophagy: physiology and pathology.
AB  - Autophagy has long been thought of as a bulk degradation system in which
      cytoplasmic components are sequestered by double-membrane structures called
      autophagosomes, and the contents are then degraded after autophagosomes fuse with
      lysosomes. Genetic experiments in yeast identified a set of Autophagy-related
      (ATG) genes that are essential for autophagy. We have since elucidated many of
      the molecular underpinnings of autophagy and the physiologic roles of these
      processes in various systems. This review summarizes the physiologic roles of
      autophagy with a particular focus on liver autophagy based on analyses of
      knockout mice lacking Atg genes.

PMID- 22661766
TI  - Competitive Outcomes of Aquatic Container Diptera Depend on Predation and
      Resource Levels.
AB  - Resources and predation are both known to be important in structuring
      communities; however the strength of one factor may be affected by the intensity
      of the other. This study used a fully crossed factorial experiment in laboratory
      microcosms to examine the ability of a predator, Corethrella appendiculata
      (Grabham), and basal resources (leaf litter) to differentially affect two
      competing species of mosquito prey. Increased resources resulted in shorter
      developmental time and increased survivorship, mass, and population performance
      for both prey species, except when predation levels were high. Increased levels
      of predation and resources reduced the negative competitive effects of Aedes
      albopictus (Skuse) on Ochlerotatus triseriatus (Say). At low levels of resources
      and predation, the superior competitor, A. albopictus had the higher
      survivorship, and at high levels of resources and predation, the inferior
      competitor's survival was greater. Predators in high-resource treatments emerged
      larger than those in low resources, suggesting the occurrence of a bottom-up
      cascade or alternative feeding method. This study suggests that survival and
      coexistence of the two prey species may depend on the interaction of resources
      and predation, in that high levels of predation are important for the coexistence
      of both species.

PMID- 22661767
TI  - EFFECTS OF ELEVATED ATMOSPHERIC CO(2) ON WATER CHEMISTRY AND MOSQUITO (DIPTERA:
      CULICIDAE) GROWTH UNDER COMPETITIVE CONDITIONS IN CONTAINER HABITATS.
AB  - We investigated the direct and indirect effects of elevated atmospheric CO(2) on
      freshwater container habitats and their larval mosquito occupants. We predicted
      that a doubling of atmospheric CO(2) would (1) alter the chemical properties of
      water in this system, (2) slow degradation of leaf litter, and (3) decrease
      larval growth of Aedes albopictus (Skuse) mosquitoes raised on that litter under
      competitive conditions. Effects of elevated CO(2) on water quality parameters
      were not detected, but the presence of leaf litter significantly reduced pH and
      dissolved oxygen relative to water-filled containers without litter. Degradation
      rates of oak leaf litter from plants grown under elevated CO(2) atmospheres did
      not differ from breakdown rates of litter from ambient CO(2) conditions. Litter
      from plants grown in an elevated CO(2) atmospheres did not influence mosquito
      population growth, but mosquito production decreased significantly with
      increasing larval density. Differences among mosquito density treatments
      influenced survivorship most strongly among male Ae. albopictus and time to
      emergence most strongly among females, suggesting fundamental sex-determined
      differences in response to competition. Results of this and other studies
      indicate that direct and indirect effects of doubled atmospheric CO(2) are
      minimal in artificial containers with freshwater.

PMID- 22661768
TI  - Translating Nature's Library: The Bryostatins and Function-Oriented Synthesis.
AB  - We review in part our computational, design, synthesis, and biological studies on
      a remarkable class of compounds and their designed analogs that have led to
      preclinical candidates for the treatment of cancer, a first-in-class approach to
      Alzheimer's disease, and a promising strategy to eradicate HIV/AIDS. Because
      these leads target, in part, protein kinase C (PKC) isozymes, they have
      therapeutic potential even beyond this striking set of therapeutic indications.
      This program has given rise to new synthetic methodology and represents an
      increasingly important direction of synthesis focused on achieving function
      through synthesis-informed design (function-oriented synthesis).

PMID- 22661769
TI  - Coresidence With Elderly Parents: A Comparative Study of Southeast China and
      Taiwan.
AB  - Using recent survey data from the Panel Study of Family Dynamics (PSFD) on 1,655
      married persons born in 1964-1976 in southeastern China and Taiwan, we studied
      coresidence with elderly parents using a multinomial probit model for coresidence
      type and an ordered probit model for residential distance. The study yielded four
      findings: (a) Patrilocal coresidence was more prevalent in Taiwan than in China;
      (b) matrilocal coresidence was more prevalent in China; (c) practical factors
      mattered in both places; (d) in Taiwan only, a couple's economic resources
      facilitated breaking away from patrilocal coresidence. The findings suggest that,
      although economic development does not necessarily result in less traditional
      familial culture, personal economic resources may enable individual couples to
      deviate from tradition.

PMID- 22661770
TI  - Reproduction of Meloidogyne marylandi and M. incognita on several Poaceae.
AB  - The susceptibility of 22 plant species to Meloidogyne marylandi and M. incognita
      was examined in three greenhouse experiments. Inoculum of M. marylandi was eggs
      from cultures maintained on Zoysia matrella "Cavalier" or Cynodon dactylon x C.
      trasvaalensis "Tifdwarf". Inoculum of M. incognita was eggs from cultures
      maintained on Solanum lycopersicum 'Rutgers'. In each host test the inoculum
      density was 2,000 nematode eggs/pot. None of the three dicot species tested
      (Gossypium hirsutum, Arachis hypogaea, and S. lycopersicum) were hosts for M.
      marylandi but, as expected, M. incognita had high levels of reproduction on G.
      hirsutum and S. lycopersicum. Meloidogyne marylandi reproduced on all of the 19
      grass species (Poaceae) tested but reproduction varied greatly (P = 0.05) among
      these hosts. The following grasses were identified for the first time as hosts
      for M. marylandi: Buchloe dactyloides (buffalograss), Echinochloa colona (jungle
      rice), Eragostis curvula (weeping lovegrass), Paspalum dilatatum (dallisgrass),
      P. notatum (bahiagrass), Sorghastrum, nutans (indiangrass), Tripsacum dactyloides
      (eastern gamagrass), and Zoysia matrella (zoysiagrass). No reproduction of M.
      incognita was observed on B. dactyloides, Cyndon dactylon (common bermudagrass),
      E. curvula, P. vaginatum (seashore paspalum), S. nutans, T. dactyloides, Z.
      matrella or Z. japonica. Reproduction of M. incognita was less than reproduction
      of M. marylandi on the other grass species, except for the Zea mays inbred line
      B73 on which M. incognita had greater reproduction than did M. marylandi (P =
      0.05) and Stenotaphrum secundatum (St. Augustinegrass) on which M. incognita and
      M. marylandi had similar levels of reproduction.

PMID- 22661771
TI  - Solanum Tuber-bearing Species Resistance Behavior Against Nacobbus aberrans.
AB  - Naccobus aberrans is a major pest of the potato crop in the Andean regions of
      Argentina, Bolivia, and Peru. It is endemic in northwest Argentina and is also
      found in lowlands. The resistance of eleven Andean potato landraces and three
      accessions of the wild tuber-bearing species Solanum acaule, S. infundibuliforme,
      and S. megistacrolobum were evaluated against a population of N. aberrans from
      Coctaca, Jujuy province, while Solanum tuberosum ssp. tuberosum 'Spunta',
      'Kennebec', and 'Frital INTA' were evaluated against a population from the
      southeast of Buenos Aires province. The presence, the number of galls, and the
      number of individuals were recorded. In addition, a reproduction factor was
      calculated and races were determined. Results showed that the N. aberrans
      population from Coctaca corresponded to race 2 and the population from the
      lowlands belonged to the sugar beet group. Landrace Azul, one genotype of S.
      megistacrolobum, and two genotypes of S. acaule showed resistance towards the
      race from Coctaca while no infection was recorded in potato cultivars with the
      Naccobus race from the lowland area.

PMID- 22661772
TI  - Pathogenic Roles of the Bacteria carried by Bursaphelenchus mucronatus.
AB  - Fifty strains of bacteria were isolated from six isolates of the nematode
      Bursaphelenchus mucronatus (Bm) from China and Russia and identified using the
      BioMerieux Vitek 32 system. In bioassay, 3 bacterial strains showed the high
      levels of phytotoxin production while 19, 16, and 12 strains showed moderately,
      low and no phytotoxin production, respectively. Inoculation of 2-month-old Pinus
      thunbergii seedling with each of the six Bm isolates showed that the mean number
      of days from inoculation to death of 80% of the seedlings was significantly
      related to the ratio of the total number of bacterial strains for a nematode
      isolate to the number of pathogenic bacterial strains of the nematode isolate.
      The results of inoculation of 3-year-old P. thunbergii seedlings showed that
      inoculation with either axenic Bm (ABm) or axenic B. xylophilus (ABx) and the
      pathogenic bacterial strain together were essential for inducing pine wilt. These
      findings demonstrate that wilt symptoms caused by Bm conform to our earlier
      hypothesis (Zhao et al., 2003) that pine wilt disease, induced by certain Bx or
      Bm isolates, is caused by a complex of both the nematodes and their associated
      pathogenic bacteria. The results also account for the variation in pathogenicity
      of Bm populations from different parts of the world.

PMID- 22661773
TI  - Early Embryogenesis and Anterior-Posterior Axis Formation in the White-Tip
      Nematode Aphelenchoides besseyi (Nematoda: Aphelenchoididae).
AB  - We followed the early embryogenesis of Aphelenchoides besseyi from fertilization
      to the 4-cell stage under Nomarski optics and examined the chromosome number and
      structure by DAPI staining. After an oocyte is fertilized by a sperm, the
      eggshell forms and the male and female pronuclei are reconstructed. The male
      pronucleus moves toward the female pronucleus, which is located at the center of
      the egg. They meet, rotate 90 degrees , and fuse. The embryo then divides
      unequally into a larger anterior AB cell and a smaller posterior P(1) cell. The
      site of sperm entry into the oocyte seems to become the future anterior pole of
      the embryo, and thus the formation of an anterior-posterior axis formation is the
      same as that for Bursaphelenchus xylophilus, but opposite to that for
      Caenorhabditis elegans. From immunostaining, the fertilizing sperm appears to
      bring the centrosome into the oocyte. The chromosome structure during the
      pronuclear meeting as observed by DAPI staining suggests that a haploid sperm (N
      = 3) fertilizes a haploid oocyte (N = 3) to form a diploid embryo (2N = 6) and
      that all chromosomes appear to be of a similar size. Unlike C. elegans does, the
      P(1) cell first divides anterior-posteriorly followed by the AB anterior
      posteriorly. These divisions produced the 4-cell stage embryo with 4 cells
      arranged in a linear fashion, again in contrast to that for C. elegans or B.
      xylophilus configured in a rhomboid shape.

PMID- 22661774
TI  - Effect of Temperature on the Embryogenesis of Geographic Populations of
      Rotylenchulus reniformis.
AB  - The effect of temperature on the embryonic development of three populations of
      reniform nematode (Rotylenchulus reniformis) from the southeastern United States
      was studied. The development of eggs from single-cell stage to eclosion of second
      stage juvenile was monitored at 20, 25, 30, and 35 degrees C. All populations
      completed embryogenesis in 7 days at 25 degrees C. The greatest differences among
      populations in time to completion of embryogenesis were observed at 20 and 35
      degrees C. Results at the intermediate temperatures (25 and 30 degrees C) were
      similar for the three populations. The optimal temperature for embryogenesis was
      calculated to be 31.4 degrees C for the population from Alabama, 28.4 degrees C
      for the one from Mississippi, and 37.5 degrees C for the one from South Carolina.

PMID- 22661775
TI  - Phylogenetic Analysis of the Hoplolaiminae Inferred from Combined D2 and D3
      Expansion Segments of 28S rDNA.
AB  - DNA sequences of the D2-D3 expansion segments of the 28S gene of ribosomal DNA
      from 23 taxa of the subfamily Hoplolaiminae were obtained and aligned to infer
      phylogenetic relationships. The D2 and D3 expansion regions are G-C rich (59.2%),
      with up to 20.7% genetic divergence between Scutellonema brachyurum and
      Hoplolaimus concaudajuvencus. Molecular phylogenetic analysis using maximum
      likelihood and maximum parsimony was conducted using the D2-D3 sequence data. Of
      558 characters, 254 characters (45.5%) were variable and 198 characters (35.4%)
      were parsimony informative. All phylogenetic methods produced a similar topology
      with two distinct clades: One clade consists of all Hoplolaimus species while the
      other clade consists of the rest of the studied Hoplolaiminae genera. This result
      suggests that Hoplolaimus is monophyletic. Another clade consisted of Aorolaimus,
      Helicotylenchus, Rotylenchus, and Scutellonema species. Phylogenetic analysis
      using the outgroup species Globodera rostocheinsis suggests that Hoplolaiminae is
      paraphyletic. In this study, the D2-D3 region had levels of DNA sequence
      divergence sufficient for phylogenetic analysis and delimiting species of
      Hoplolaiminae.

PMID- 22661777
TI  - Cloning, Sequence, and Expression Analysis of a New MnSOD-Encoding Gene from the
      Root-Knot Nematode Meloidogyne incognita.
AB  - A gene encoding a manganese superoxide dismutase (MnSOD) enzyme (Mi-mnsod) was
      identified and characterized in second-stage juveniles of the root-knot nematode
      Meloidogyne incognita. The Mi-mnsod gene was found to possess five exons and four
      introns with (GT/AG) consensus splice-site junctions. The deduced amino acid
      sequence of Mi-mnsod encodes a putative 25 KDa protein, with conserved amino acid
      residues of the MnSOD family, including the Parker-Blake signature and four metal
      binding sites. The derived amino acid sequence showed high similarity to other
      eukaryotic MnSODs, including a 23 amino acid N-terminal putative mitochondrial
      transit peptide. Gene expression was observed throughout the posterior nematode
      body region with elevated signal intensities at the anterior portion of the
      intestine. DNA blot analysis and sequencing data showed the occurrence of three
      putative copies of the MnSOD gene with nucleotide polymorphisms found at the
      fourth exon and the 3' un-translated region.

PMID- 22661776
TI  - Duplication and divergence: the evolution of nematode globins.
AB  - In common with many other groups, nematodes express globins with unknown
      functions. Nematode globin-like genes can be divided into class 1 globins,
      similar to vertebrate myoglobins, and a wide range of additional classes. Here we
      show that class 1 nematode globins possess a huge amount of diversity in gene
      sequence and structure. There is evidence for multiple events of gene
      duplication, intron insertion and loss between species, and for allelic variation
      effecting both synonymous and non-synonymous sites within species. We have also
      examined gene expression patterns in class I globins from a variety of species.
      The results show variation in the degree of gene expression, but the tissue
      specificity and temporal specificity of expression may be more conserved in the
      phylum. Because the structure-function relationships for the binding and
      transport of oxygen by globins are well understood, the consequences of genetic
      variation causing amino acid changes are explored. The gene family shows great
      promise for discovering unique insights into both structure-function
      relationships of globins and their physiologial roles.

PMID- 22661778
TI  - Rapid Detection of Tobacco Rattle Tobravirus in Viruliferous Paratrichodorus
      allius from Greenhouse and Field Specimens.
AB  - The stubby root nematode, Paratrichodorus allius, is important to the potato
      industry in the Pacific Northwest of USA, because it vectors Tobacco rattle virus
      (TRV), the causal agent of corky ringspot disease. The current method for
      determining if nematodes are viruliferous for TRV takes several weeks, requiring
      a glasshouse bioassay followed by a serological test. To overcome this drawback,
      a rapid and affordable molecular test was developed using reverse transcription
      polymerase chain reaction (RT-PCR) to identify viruliferous P. allius nematodes
      within 48 hours. Primers from the 16 kDa gene of TRV were used to detect TRV in
      both greenhouse-reared and field collected P. allius. TRV RNA can be detected
      consistently in nucleic acids equivalent to one quarter of a viruliferous adult
      nematode reared in the greenhouse. In order to reduce the time and expense of
      processing individual nematodes from field samples, viral RNA was consistently
      and affordably detected in extracts from 5 field-collected adult P. allius.

PMID- 22661779
TI  - A partial revision of the marine nematode genus elzalia (monhysterida: xyalidae)
      with new characters and descriptions of two new species from khung kraben bay,
      East Thailand.
AB  - Elzalia bipectinellan. sp. and E. tuberculatan. sp. from Thailand are described
      and the males of three species from the Gulf of Mexico, E. federiciCastillo
      Fernandez and Lambshead (1990), E. kimaeCastillo-Fernandez and Lambshead (1990),
      and E. poliCastillo-Fernandez and Lambshead (1990) are re-described from type and
      topotype specimens using light and scanning electron microscopy. New
      morphological characters are described that include ornamentations at the distal
      end of the spicula and features of the gubernaculum including the manus with
      digits, pontis with sensory receptor and accessory process, and the condylus with
      either conical or foliate projections. Also, ejaculatory and rectal glands are
      described for the first time for Elzalia. The relevance of the new characters to
      the taxonomy of Elzalia is discussed. A key to identification of males is
      provided. A generalized description of females is given, although characters are
      lacking by which females of each species may be identified.

PMID- 22661781
TI  - Three New Species of Brevitobrilus (Nematoda) with a Discussion on Relationships
      within the Genus.
AB  - Three new species of the genus BrevitobriusTsalolikhin, 1981 are described.
      Brevitobrilus glandulatus n. sp. is characterized by conspicuous sphincter
      between pars dilatata and uterus; two pairs of vaginal glands; spicules having
      elliptical capitula with small proximal stiffening piece; proximally-arcuate
      gubernaculum; S3 and S4 smaller than other supplements; S6 out of spicular range
      and 57-60 micropapillae. Brevitobrilus dimorphicus n. sp. is diagnosed by sexual
      dimorphism in labial sensilla and amphids; thick-walled rectum with a
      diverticulum protruding into intestinal lumen and males with boat-shaped spicules
      and S6 occasionally slightly smaller than other supplements. Brevitobrilus
      allahabadensis n. sp. possesses large amphids of 28-33% of corresponding labial
      diameter in both sexes; vagina and uterus with muscular, plicate walls; well
      developed sphincter between vas deferens and ejaculatory duct; capitulate
      spicules with sloping ventral and angular dorsal walls; S3, S4 and S6 smaller
      than other supplements, S6 close to cloaca and 28-37 micropapillae. The
      relationships of the species of genus Brevitobrilus have been assessed using
      morphological characters subjected to parsimony and a non cladistic key to
      identification of species is given.

PMID- 22661780
TI  - Granite rock outcrops: an extreme environment for soil nematodes?
AB  - We studied soil nematode communities from the surface of granite flatrock
      outcrops in the eastern Piedmont region of the United States. The thin soils that
      develop here experience high light intensity and extreme fluctuations in
      temperature and moisture and host unique plant communities. We collected soils
      from outcrop microsites in Virginia (VA) and North Carolina (NC) in various
      stages of succession (Primitive, Minimal, and Mature) and compared soil
      properties and nematode communities to those of adjacent forest soils. Nematodes
      were present in most outcrop soils, with densities comparable to forest soils (P
      > 0.05). Nematode communities in Mature and Minimal soils had lower species
      richness than forest soils (P < 0.05) and contained more bacterial-feeders and
      fewer fungal-feeders (P < 0.05). Primitive soils contained either no nematodes
      (NC) or only a single species (Mesodorylaimus sp., VA). Nematode communities were
      similar between Mature and Minimal soils, according to trophic group
      representation, MI, PPI, EI, SI, and CI (P > 0.05). Forest soils had a higher PPI
      value (P < 0.05), but otherwise community indices were similar to outcrop soils
      (P > 0.05). Outcrop nematode communities failed to group together in a Bray
      Curtis cluster analysis, indicating higher variability in community structure
      than the Forest soils, which did cluster together. A high proportion of the
      nematodes were extracted from outcrop soils in coiled form (33-89%), indicating
      that they used anhydrobiosis to persist in this unique environment.

PMID- 22661782
TI  - Longidorus ferrisi n. sp. from California Citrus.
AB  - In October 1999, the authors received fixed specimens of a species of Longidorus
      from Howard Ferris found about the roots of a citrus tree in Oakville, Napa
      County, CA. After determining it to be new a species, we requested additional
      specimens. The samples contained roughly equal numbers of males and females.
      Longidorus ferrisi n. sp. is most similar to L. elongatus, but can be
      distinguished by a greater c-ratio (111-187 vs 73-141), a lesser c' (0.7-1.1 vs
      1.0-1.3), a more offset head, a more posterior guide ring (35-40 vs 30-33 MUm),
      the presence of sperm in the uterus in mature females, and the approximate 1:1
      ratio of females to males. Other similar species include L. artemisiae, L.
      crassus, L. glycines, and L. milanis. Longidorus ferrisi n. sp. differs from L.
      artemisiae by a lesser a-ratio (74-102 vs 109-155), a lesser c' value (0.7-1.1 vs
      1.0-1.6), a more posterior guide ring (35-40 vs 27-34 MUm), a longer odontostyle
      (91-108 vs 84-98 MUm), a wider lip region (16-19 vs 14-17 MUm), wider mid-body
      (53-69 vs 41-52 MUm), and longer spicules (57-65 vs 39-49 MUm). The new species
      differs substantially from L. crassus by its lip shape and the presence of males,
      and differs from L. glycines by a shorter body (4.33-5.97 vs 6.14-8.31 mm), a
      lesser c' value (0.7-1.1 vs 0.9-1.4), a narrower lip region (16-19 vs 20-23 MUm),
      wider mid-body (53-69 vs 39-57 MUm), longer spicules (53-69 vs 45-53 MUm), and
      fewer supplements (7-11 vs 11-17). Longidorus ferrisi n. sp. differs from L.
      milanis by a longer body (4.33-5.97vs 3.00-4.90 mm), a greater c value (111-187
      vs 86-130), a wider mid-body (53-69 vs 43-56 MUm), a different head shape, and
      longer spicules (53-69 vs 41-54 MUm). The nuclear 18S ribosomal DNA sequence of
      this species revealed that this species is unique with respect to all sequenced
      Longidorus species.

PMID- 22661783
TI  - Xiphinema bernardi n. sp. (Nematoda: Longidoridae) from the Great Smoky Mountain
      National Park.
AB  - In October 1985 during a survey of fauna of the Great Smoky Mountains National
      Park, Ernest Bernard recovered a limited number of specimens of a non-described
      species of Xiphinema (Nematoda: Longidoridae) and sent them to the senior author.
      The species is distinct from other species by its large size and having Z-organs
      in the genital tract. During July 2006, Dr. Bernard's survey crew took samples in
      the area where the species was first found and was successful in finding it
      again. Without Dr. Bernard's efforts, this species could not have been described
      and thus the new species is named X. bernardi n. sp. in his honor. Several female
      and juvenile specimens of the new species were recovered in a sample from a mixed
      forest of maple, hemlock, and silverbell. It is distinct from all others in
      Xiphinema group 4 species (with Z-organs) by having a longer total stylet length,
      259.8 to 284.2 MUm vs < 253 MUm for all other species in this group. Xiphinema
      bernardi n. sp. is distinctive because of its long body length (4.45 to 6.00 mm),
      tail shape, and c' ratio. Of the group 4 species, it most closely resembles X.
      phoenicis. Second, third and fourth stage juvenile descriptions and morphometrics
      are included. The polytomous key code for X. bernardi n. sp. is A4-B1-C6-D56-E56
      F(4)5-G4-H2-I34-J5-K?-L1. Molecular approaches using the internal transcribed
      spacer 1 sequences of nuclear ribosomal DNA suggested that X. bakeri and X.
      diversicaudatum are the most closely related species from the species examined.

PMID- 22661784
TI  - Distribution and Prevalence of Parasitic Nematodes of Cowpea (Vigna unguiculata)
      in Burkina Faso.
AB  - A comprehensive survey of the plant parasitic nematodes associated with cowpea
      (Vigna unguiculata) production fields was carried out in the three primary agro
      climatic zones of Burkina Faso in West Africa. Across the three zones, a total of
      109 samples were collected from the farms of 32 villages to provide a
      representative coverage of the cowpea production areas. Samples of rhizosphere
      soil and samples of roots from actively growing cowpea plants were collected
      during mid- to late-season. Twelve plant-parasitic nematode genera were
      identified, of which six appeared to have significant parasitic potential on
      cowpea based on their frequency and abundance. These included Helicotylenchus,
      Meloidogyne, Pratylenchus, Scutellonema, Telotylenchus, and Tylenchorhynchus.
      Criconemella and Rotylenchulus also had significant levels of abundance and
      frequency, respectively. Of the primary genera, Meloidogyne, Pratylenchus, and
      Scutellonema contained species which are known or suspected to cause losses of
      cowpea yield in other parts of the world. According to the prevalence and
      distribution of these genera in Burkina Faso, their potential for damage to
      cowpea increased from the dry Sahelian semi-desert zone in the north (annual
      rainfall < 600 mm/year), through the north-central Soudanian zone (annual
      rainfall of 600-800 mm/year), to the wet Soudanian zone (annual rainfall >= 1000
      mm) in the more humid south-western region of the country. This distribution
      trend was particularly apparent for the endoparasitic nematode Meloidogyne and
      the migratory endoparasite Pratylenchus.

PMID- 22661785
TI  - Distribution and Identification of Root-knot Nematodes from Turkey.
AB  - Root knot nematodes are causing serious losses in protected cultivation fields in
      the West Mediterranean region of Turkey. Correct and confident identification of
      the plant parasitic nematodes is important for vegetable growing and breeding.
      Therefore, ninety-five populations of plant parasitic nematodes were collected
      from regional greenhouses. Previously described species-specific primers were
      used to identify Meloidogyne populations. The present study indicated that SEC
      1F/SEC-1R and INCK14F-INCK14R primers for identifying of M. incognita, Fjav/Rjav
      and DJF/DJR primers for M. javanica and Far/Rar for M. arenaria primers can be
      effective tools to identify the Turkish root-knot nematode species. Dissemination
      ratios of the population were 64.2%, 28.4% and 7.3% for Meloidogyne incognita, M.
      javanica and M. arenaria, respectively. The results showed that M. incognita was
      the prominent root-knot nematode species in the West Mediterranean coastal areas
      of Turkey.

PMID- 22661786
TI  - Effects of the Mi-1 and the N root-knot nematode-resistance gene on infection and
      reproduction of Meloidogyne enterolobii on tomato and pepper cultivars.
AB  - Meloidogyne enterolobii is widely considered to be an aggressive root-knot
      nematode species that is able to reproduce on root-knot nematode-resistant tomato
      and pepper cultivars. In greenhouse experiments, M. enterolobii isolates 1 and 2
      from Switzerland were able to reproduce on tomato cultivars carrying the Mi-1
      resistance gene as well as an N-carrying pepper cultivar. Reproduction factors
      (Rf) ranged between 12 and 109 depending on the plant cultivar, with M.
      enterolobii isolate 2 being more virulent when compared to isolate 1. In
      contrast, M. arenaria completely failed to reproduce on these resistant tomato
      and pepper cultivars. Although some variability in virulence and effectiveness of
      root-knot nematode-resistance genes was detected, none of the plant cultivars
      showed Rf values less than 1 or less than 10% of the reproduction observed on the
      susceptible cv. 'Moneymaker' (Rf = 23-44) used to characterize resistance. The
      ability of M. enterolobii to overcome the resistance of tomato and pepper
      carrying the Mi-1 and the N gene makes it difficult to manage this root-knot
      nematode species, particularly in organic farming systems where chemical control
      is not an option.

PMID- 22661787
TI  - The multi-year effects of repeatedly growing cotton with moderate resistance to
      Meloidogyne incognita.
AB  - Meloidogyne incognita causes more damage to cotton in the US than any other
      pathogen. The objective of this study was to document the cumulative effect of
      moderate resistance on M. incognita population density, root galling, and yield
      suppression in the southern United States on a moderately resistant cotton
      genotype grown continuously for three years. Cotton genotypes were Phytogen PH98
      3196 (77% suppression of M. incognita), Acala NemX (85% suppression of M.
      incognita), and Delta and Pine Land DP458 B/R (susceptible standard, 0%
      suppression). Cotton was grown in fumigated and non-fumigated plots to measure
      yield loss. Each genotype and nematicide combination was planted in the same
      place for three years at two sites to document cumulative effects. In 2006,
      following three years of the different genotypes, all plots at one site were
      planted with susceptible cotton to document residual effects of planting
      resistant genotypes. Root galling and nematode population densities in the soil
      were significantly lower, and percentage yield suppression was numerically lower,
      when moderately resistant cotton was grown compared to the susceptible standard
      in both fields in all three years. Differences between susceptible and moderately
      resistant genotypes are established quickly (after only one season) and then
      either maintained at similar levels or slightly increased in subsequent years
      depending on initial nematode levels. However, when susceptible cotton was grown
      following three years of the moderately resistant genotypes, the nematode
      suppression provided by moderate resistance was undetectable by the end of the
      first season. Moderately resistant cotton genotypes are more beneficial than
      previously reported and should be pursued for nematode management. Rotation of
      moderately resistant and susceptible cotton could be used along with nematicides
      to manage root-knot nematodes in a continuous cotton cropping system and reduce
      selection pressure on the nematodes.

PMID- 22661789
TI  - Pathogenicity of the pinewood nematode, Bursaphelenchus xylophilus, to Japanese
      larch, Larix kaempferi, seedlings.
AB  - Pathogenicity of the pine wood nematode, Bursaphelenchus xylophilus, to Japanese
      larch, Larix kaempferi, seedlings was tested with inoculation experiments under
      nursery conditions. Water suspensions of nematodes (mixed stages cultured on
      Botrytis cinerea or dispersal fourth-stage juveniles (DJ4) extracted from the
      adult Japanese pine sawyer, Monochamus alternatus) were injected into the stems
      of 2- and 3-year-old Japanese larch and Japanese black pine, Pinus thunbergii,
      seedlings growing in a nursery. In another treatment, Japanese pine sawyer adults
      holding DJ4 were released under a net that covered the upper half of the
      seedlings. Regardless of nematode inoculation method, Japanese larch seedlings
      were as susceptible as Japanese black pine seedlings to B. xylophilus under
      nursery conditions. The rate of disease development was similar on larch and pine
      seedlings. Nematode population densities were lower in the stems of dead larch
      seedlings than in the stems of dead pine seedlings. Histopathological
      observations revealed that the distribution of nematodes in the stems of dead
      larch seedlings was mostly limited to the cortex, phloem and cambial zone.
      Traumatic resin canal formation was one of the most characteristic symptoms in
      larch seedlings which was dissimilar to that in pine seedlings.

PMID- 22661788
TI  - Microsatellites reveal genetic diversity in Rotylenchulus reniformis populations.
AB  - Rotylenchulus reniformis is the predominant parasitic nematode of cotton in the
      Mid South area of the United States. Although variable levels of infection and
      morphological differences have been reported for this nematode, genetic
      variability has been more elusive. We developed microsatellite-enriched libraries
      for R. reniformis, produced 1152 clones, assembled 694 contigs, detected 783
      simple sequence repeats (SSR) and designed 192 SSR-markers. The markers were
      tested on six R. reniformis cultures from four states, Texas, Louisiana,
      Mississippi and Georgia, in the USA. Based on performance we selected 156 SSR
      markers for R. reniformis from which 88 were polymorphic across the six reniform
      nematode populations, showing as the most frequent motif the dinucleotide AG. The
      polymorphic information content of the markers ranged from 0.00 to 0.82, and the
      percentage of multiallelic loci of the isolates was between 40.9 and 45.1%. An
      interesting finding in this study was the genetic variability detected among the
      three Mississippi isolates, for which 22 SSR markers were polymorphic. We also
      tested the level of infection of these isolates on six cotton genotypes, where
      significant differences were found between the Texas and Georgia isolates.
      Coincidentally, 62 polymorphic markers were able to distinguish these two
      populations. Further studies will be necessary to establish possible connections,
      if any, between markers and level of pathogenicity of the nematode. The SSR
      markers developed here will be useful in the assessment of the genetic diversity
      of this nematode, could assist in management practices for control of reniform
      nematode, be used in breeding programs for crop resistance, and help in detecting
      the origin and spread of this nematode in the United States.

PMID- 22661790
TI  - HIGH DIMENSIONAL COVARIANCE MATRIX ESTIMATION IN APPROXIMATE FACTOR MODELS.
AB  - The variance covariance matrix plays a central role in the inferential theories
      of high dimensional factor models in finance and economics. Popular
      regularization methods of directly exploiting sparsity are not directly
      applicable to many financial problems. Classical methods of estimating the
      covariance matrices are based on the strict factor models, assuming independent
      idiosyncratic components. This assumption, however, is restrictive in practical
      applications. By assuming sparse error covariance matrix, we allow the presence
      of the cross-sectional correlation even after taking out common factors, and it
      enables us to combine the merits of both methods. We estimate the sparse
      covariance using the adaptive thresholding technique as in Cai and Liu (2011),
      taking into account the fact that direct observations of the idiosyncratic
      components are unavailable. The impact of high dimensionality on the covariance
      matrix estimation based on the factor structure is then studied.

PMID- 22661792
TI  - Cognitive Constraints and Island Effects.
AB  - Competence-based theories of island effects play a central role in generative
      grammar, yet the graded nature of many syntactic islands has never been properly
      accounted for. Categorical syntactic accounts of island effects have persisted in
      spite of a wealth of data suggesting that island effects are not categorical in
      nature and that non-structural manipulations that leave island structures intact
      can radically alter judgments of island violations. We argue here, building on
      work by Deane, Kluender, and others, that processing factors have the potential
      to account for this otherwise unexplained variation in acceptability judgments.We
      report the results of self-paced reading experiments and controlled acceptability
      studies which explore the relationship between processing costs and judgments of
      acceptability. In each of the three self-paced reading studies, the data indicate
      that the processing cost of different types of island violations can be
      significantly reduced to a degree comparable to that of non-island filler-gap
      constructions by manipulating a single non-structural factor. Moreover, this
      reduction in processing cost is accompanied by significant improvements in
      acceptability. This evidence favors the hypothesis that island-violating
      constructions involve numerous processing pressures that aggregate to drive
      processing difficulty above a threshold so that a perception of unacceptability
      ensues. We examine the implications of these findings for the grammar of filler
      gap dependencies.

PMID- 22661791
TI  - Detecting Fleeting MRI Signals with Frequency-Modulated Pulses.
AB  - We describe a fundamentally different approach to MRI referred to as SWIFT (sweep
      imaging with Fourier transformation). SWIFT exploits time-shared RF excitation
      and signal acquisition, allowing capture of signal from spins with extremely
      short transverse relaxation time, T(2)*. The MR signal is acquired in gaps
      inserted into a broadband frequency-swept excitation pulse, which results in
      acquisition delays of only 1 - 2 microseconds. In SWIFT, 3D k-space is sampled in
      a radial manner, whereby one projection of the object is acquired in the gaps of
      each frequency-swept pulse, allowing a repetition time (TR) on the order of the
      pulse length (typically 1 - 3 milliseconds). Since the orientation of consecutive
      projections varies in a smooth manner (i.e., only small increments in the values
      of the x, y, z gradients occur from view to view), SWIFT scanning is close to
      inaudible and is insensitive to gradient timing errors and eddy currents. SWIFT
      images can be acquired in scan times similar to and sometimes faster than
      conventional 3D gradient echo techniques. With its ability to capture signals
      from ultrashort T(2)* spins, SWIFT promises to expand the role of MRI in areas of
      research where MRI previously played no or negligible role. In this article, we
      show wood and tooth images obtained with SWIFT as examples of materials with
      ultrashort T(2)*. Early experience suggests SWIFT can play a role in materials
      science and porous media research.

PMID- 22661793
TI  - Appraisal patterns of envy and related emotions.
AB  - Envy is a frustrating emotion that arises from upward social comparison. Two
      studies investigated the appraisals that distinguish benign envy (aimed at
      improving one's own situation) from malicious envy (aimed at pulling down the
      superior other). Study 1 found that appraisals of deservingness and control
      potential differentiated both types of envy. We manipulated these appraisals in
      Study 2 and found that while both did not influence the intensity of envy, they
      did determine the type of envy that resulted. The more a situation was appraised
      as undeserved, the more participants experienced malicious envy. Benign envy was
      experienced more when the situation was not undeserved, and the most when the
      situation was appraised as both deserved and controllable. The current research
      also clarifies how the types of envy differ from the related emotions admiration
      and resentment.

PMID- 22661794
TI  - Effects of Mindfulness-Based Cognitive Therapy on Specificity of Life Goals.
AB  - This study explored the immediate effects of a course of Mindfulness-Based
      Cognitive Therapy (MBCT) for chronically depressed participants with a history of
      suicidality on the specificity of important goals for the future. Participants
      were randomly allocated to immediate treatment with MBCT or to a waitlist
      condition and life goals were assessed both before and after the treatment or
      waiting period. Results showed that participants receiving MBCT reported
      significantly more specific goals post-treatment whereas those allocated to the
      waitlist condition showed no significant change. Similarly, participants
      allocated to MBCT regarded themselves as significantly more likely to achieve
      their important goals post-treatment, whilst again there was no significant
      change in the waitlist group. Increases in goal specificity were associated with
      parallel increases in autobiographical memory specificity whereas increases in
      goal likelihood were associated with reductions in depressed mood. These results
      suggest that MBCT may enable participants to clarify their important goals and in
      doing so increase their confidence in their capacity to move in valued life
      directions.

PMID- 22661795
TI  - Disgust Propensity as a Predictor of Intrusive Cognitions Following a Distressing
      Film.
AB  - Although extant research examining predictors of development of Posttraumatic
      Stress Disorder (PTSD) have focused primarily on fear and anxiety, recent
      research suggests that a range of different emotional reactions may occur in
      response to traumatic events. For example, specific aspects of traumatic exposure
      frequently include either experiencing or witnessing events that may elicit
      disgust, including injury, death, or sexual assault (e.g., Dalgleish and Power in
      Behav Res Ther Spec Issue Festschrift Spec Issue John Teasdale 42(9):1069-1088,
      2004); McNally in J Anxiety Disord 16(5):561-566, 2002). However, no published
      research has specifically examined the role of disgust propensity in the
      development and maintenance of PTSD. Thus, the aim of the present study was to
      evaluate the relationship between disgust propensity and intrusive symptoms. To
      this end, 30 undergraduates without symptoms of PTSD were recruited to
      participate in a distressing film paradigm (for a review of this paradigm see
      Holmes and Bourne in Acta Psychol 127(3):553-566, 2008). Anxiety, depression, and
      trait disgust scores were entered hierarchically into a regression equation to
      predict the number of intrusions during a post-film thought monitoring period.
      Results indicated that disgust propensity predicted intrusions independent of
      anxiety and depression. Although still preliminary, results suggest that disgust
      propensity may be one factor that predicts frequency of intrusive memories after
      witnessing injury or bodily harm.

PMID- 22661796
TI  - An Evaluation of 3-D Scene Exploration Using a Multiperspective Image Framework.
AB  - Multiperspective images (MPIs) show more than what is visible from a single
      viewpoint and are a promising approach for alleviating the problem of occlusions.
      We present a comprehensive user study that investigates the effectiveness of MPIs
      for 3-D scene exploration. A total of 47 subjects performed searching, counting,
      and spatial orientation tasks using both conventional and multiperspective
      images. We use a flexible MPI framework that allows trading off disocclusion
      power for image simplicity. The framework also allows rendering MPI images at
      interactive rates, which enables investigating interactive navigation and dynamic
      3-D scenes. The results of our experiments show that MPIs can greatly outperform
      conventional images. For searching, subjects performed on average 28% faster
      using an MPI. For counting, accuracy was on average 91% using MPIs as compared to
      42% for conventional images.

PMID- 22661797
TI  - Qualitative exporation of relationships with important non-parental adults in the
      lives of youth in foster care.
AB  - Foster youth are at risk of poor adult outcomes. Research on the role of
      mentoring relationships for this population suggests the value of strategies that
      increase their access to adult sources of support, both while in foster care and
      as they reach adulthood. We conducted semi-structured, individual qualitative
      interviews with 23 former foster youth ages 18-25 regarding their relationships
      with supportive non-parental adults. We sought to identify factors that influence
      the formation, quality, and duration of these relationships and to develop
      testable hypotheses for intervention strategies. Findings suggest several themes
      related to relationship formation with non-parental adults, including barriers
      (e.g., youth's fears of being hurt) and facilitators (e.g., patience from the
      adult). Distinct themes were also identified relating to the ongoing development
      and longevity of these relationships. Youth also described multiple types of
      support and positive contributions to their development. Proposed intervention
      strategies include systematic incorporation of important non-parental adults into
      transition planning, enhanced training and matching procedures within formal
      mentoring programs, assistance for youth to strengthen their interpersonal
      awareness and skills, and the targeting of specific periods of need when linking
      youth to sources of adult support. Recommended research includes the development,
      pilot-testing, and evaluation of proposed strategies.

PMID- 22661799
TI  - The bipolar spectrum.

PMID- 22661798
TI  - Impact of Intensive Case Management on Child Welfare System Involvement for
      Substance-Dependent Parenting Women on Public Assistance.
AB  - This study examined the impact of intensive case management (ICM) on decreasing
      child welfare system involvement in a sample of substance-dependent parenting
      women who participated in a welfare demonstration study comparing ICM to usual
      screen-and-refer models employed in welfare settings. Previous research
      established the effectiveness of ICM in both increasing engagement in substance
      abuse treatment and in promoting abstinence, and the current study tested whether
      ICM had downstream impacts on child welfare outcomes not directly targeted by the
      intervention. The sample included 302 mothers recruited from welfare offices and
      their 888 minor children. Child welfare outcomes were available from
      administrative records for four years following study entry and included incident
      reports and out-of-home child placements. An initial positive effect of ICM was
      found on child placements, but its impact lessened over time and was likely due
      to the increased contact with case managers that occurred early in the study.
      Overall, minimal benefits of ICM were found, suggesting that while ICM was
      effective in the areas of treatment engagement and abstinence, there were no
      downstream benefits for child welfare outcomes. Implications of findings in terms
      of increased need for cross-system collaboration are discussed.

PMID- 22661800
TI  - Reviewing two types of addiction - pathological gambling and substance use.
AB  - Gambling, including pathological gambling and problem gambling, has received
      increased attention from clinicians and researchers over the past three decades
      since gambling opportunities have expanded around the world. Gambling disorders
      affect 0.2-5.3% of adults worldwide, although measurement and prevalence varies
      according to the screening instruments and methods used, and availability and
      accessibility of gambling opportunities. Several distinct treatment approaches
      have been favorably evaluated, such as cognitive behavioral and brief treatment
      models and pharmacological interventions. Although promising, family therapy and
      support from Gamblers Anonymous are less well empirically supported. Gambling
      disorders are highly comorbid with other mental health and substance use
      disorders, and a further understanding is needed of both the causes and treatment
      implications of this disorder. This article reviews definition, causes and
      associated features with substance abuse, screening and diagnosis, and treatment
      approaches.

PMID- 22661801
TI  - Expressed emotion in schizophrenia: an overview.
AB  - The expressed emotion (EE) is considered to be an adverse family environment,
      which includes the quality of interaction patterns and nature of family
      relationships among the family caregivers and patients of schizophrenia and other
      psychiatric disorders. Influence of EE has been found to be one of the robust
      predictors of relapse in schizophrenia. This review article aims to provide a
      brief description of the origins and evolution of the EE as a construct from the
      available literature. The EE is modulated by multiple factors-some of which
      include certain personality profile, attribution factors by caregivers toward
      patient symptoms, and patient's vulnerability to stress. The psychosocial
      assessment and interventions specifically focused on family psychoeducation can
      potentially reduce high EE and relapse of symptoms as well. However, the theory
      surrounded with EE undermines the caregiver's positive attitudes toward the
      patients. Hence, it is important that the future studies should focus on both
      protective and vulnerable factors within the construct of EE in schizophrenia to
      facilitate comprehensive care.

PMID- 22661802
TI  - Boundary crossings and violations in clinical settings.
AB  - Principles of beneficence, autonomy, and nonmaleficence, compassion along with
      fiduciary partnership are the core concepts in the doctor-patient relationship in
      therapeutic settings. There are varieties of reasons for boundary problems.
      Physicians ignorance, exploitative character, emotional vulnerability moral
      weakness and similar factors may pave the way for boundary issues resulting in
      nonsexual or sexual boundary crossings and violations.

PMID- 22661803
TI  - Suggested statistical reporting guidelines for clinical trials data.
AB  - Statistical methods are widely accepted tools for analyzing data and drawing
      appropriate conclusions. However, inappropriate statistical methods may lead to
      unsuitable or false conclusions. Statistical quality of articles published in
      Indian medical journals presents with statistical fallacies and very few attempts
      have been done to document it till date. Issues related to inappropriate use of
      statistic in interpreting clinical trial raises serious doubt about the validity
      of the results published and there generalization to patient population. Clinical
      trials are considered to have one of the highest evidences in terms of efficacy
      of any intervention and hence results reported in these clinical trials help in
      appropriate decision making in clinical practices. Present manuscript is an
      attempt to have an insight into issues related to inappropriate use of statistic
      during clinical trials and suggests possible methods by which such fallacies can
      be averted.

PMID- 22661804
TI  - A study of association of depressive symptoms among the type 2 diabetic
      outpatients presenting to a tertiary care hospital.
AB  - BACKGROUND: The prevalence of diabetes mellitus is increasing among Indian
      population over time. There are varying reports about the association of
      depression among type 2 diabetic individuals. However, there is limited data
      about this in India. AIMS: To study the association of depression, demographic
      and socio-medical factors in type 2 diabetes patients. SETTINGS AND DESIGN: Cross
      sectional, epidemiological study. MATERIALS AND METHODS: All the consenting type
      2 diabetes mellitus patients attending to Medical OPD (n=210) were screened for
      symptoms of depression using beck depression inventory. All the participants were
      physically examined and a detailed psychiatric assessment were done. The relevant
      investigations were advised to identify comorbid conditions. STATISTICAL
      ANALYSIS: Chi-square test with odd's ratio. RESULTS: One-fourth of the screened
      diabetic patients were found to be having depression. Females and overweight
      individuals were found to have features of depression. Patients with long
      duration of diabetes and on combination of antidiabetic drugs were significantly
      associated with depression. Among depressed diabetics 25.9% were having Ischemic
      heart disease as a comorbid medical illness. CONCLUSIONS: This study shows there
      is increased rate of depression among type 2 diabetic individuals. The
      interesting association of depression with several demographic and sociomedical
      factors have an important implication in type 2 diabetics.

PMID- 22661805
TI  - Attention-deficit/Hyperactivity Disorder in Children: Clinical Profile and Co
      morbidity.
AB  - BACKGROUND: To study the clinical profile and co-morbidity in Indian children
      with attention-deficit/hyperactivity disorder (ADHD). MATERIALS AND METHODS: A
      prospective analytical study of 2 years duration at the Child Guidance Clinic of
      a pediatric tertiary care hospital in a south Indian city using Diagnostic and
      statistical manual of Mental Disorders-1V based questionnaires. RESULTS: Of the
      251 referrals, 51 (20.3%) children met the inclusion criteria for the diagnosis
      of ADHD. M:F ratio was 6.3:1. The mean age was 5.7 years. A majority of the
      children belonged to middle and lower socio-economic class and were first-born
      children. Most children were brought up in nuclear families. History of delayed
      speech and language development was commonly seen in these children. Combined
      type of ADHD was the most common type. At least one co-morbid diagnosis was seen
      in 86.3% of children, and learning disability was the most common co-morbid
      diagnosis. The mean IQ was 90 (SD+/-12). CONCLUSION: Early markers of cognitive
      dysfunction like delayed speech, language and social and adaptive development may
      be a pointer towards the diagnosis of ADHD in children. Knowledge about their
      sociodemographic profile and other co-morbid conditions that are associated with
      ADHD is necessary to fully understand the magnitude of the problem and to plan
      effective therapy for them.

PMID- 22661806
TI  - Psychiatric morbidity in geriatric population in old age homes and community: a
      comparative study.
AB  - BACKGROUND: The phenomenon of population ageing is already a major social and
      health problem in the developed countries. The elderly have their problems of
      disease and disability due the increasing age and changing social circumstances
      and the need for social support forms an important aspect of geriatric
      healthcare. AIM: To comparatively study the prevalence and pattern of psychiatric
      disorders in geriatric population in old age homes with those living with the
      families; and its association with the sociodemographic variables. MATERIALS AND
      METHODS: Brief Psychiatric Rating Scale was used to screen the study population
      for psychotic and non-psychotic symptoms. Mini Mental Status Examination was used
      to assess the cognitive decline and the Psychiatric diagnosis was made according
      to International classification of diseases 10(th) Revision Diagnostic criteria.
      SPSS-16 was used for statistical analysis. RESULTS: Psychiatric disorders were
      more prevalent in individuals aged >80 years, in females, and illiterates. Mood
      disorders were the most common Psychiatric disorders. Individuals in old age
      homes had less prevalence of Psychiatric illness than those living in the
      community. CONCLUSION: The overall prevalence of Psychiatric disorders was less
      in the geriatric population in old age homes because of the better availability
      of care, being engaged in regular activities as per the schedule, group works,
      etc. This study reflects the importance of delivery of care for better life in
      geriatric population.

PMID- 22661807
TI  - Schizophrenia - insight, depression: a correlation study.
AB  - BACKGROUND: Schizophrenia is one of the severe forms of mental illness which
      demands enormous personal and economical costs. Recent years have attracted
      considerable interest in the dual problem of depression in schizophrenia and its
      relation to insight. Most clinicians believe that poor insight in patients with
      schizophrenia, though problematic for treatment adherence, may be protective with
      respect to suicide. The assumption is that patients who do not believe that they
      are ill are less likely to be suicidal. Alternatively, those patients with
      schizophrenia who recognize and acknowledge the illness will be more of a
      suicidal nature. AIM OF THE STUDY: The aim of the study is to find out the
      correlation between insight and depression in schizophrenic population. MATERIALS
      AND METHODS: This study is a cross-sectional, single-centred, correlation study
      done in a total of 60 subjects. Inclusion Criteria - Subjects between 20-60
      years, who were diagnosed to have schizophrenia as per International
      clasification of diseases-10 and who have given written consent to participate in
      the study. Exclusion Criteria - Subjects who have other diagnosis such as mood
      disorder, schizoaffective disorder, mental retardation, epilepsy or detectable
      organic disease and co morbid substance abuse are excluded from the study.
      Schizophrenics who have acute exacerbation are also excluded. Instruments - For
      insight assessment, schedule for assessment of insight, a three item rating
      scale, is used. For depressive symptoms assessment a nine item rating scale,
      Calgary depression rating scale, is administrated. RESULTS: Insight and
      depression are strongly correlated in schizophrenic population with a Pearson
      correlation coefficient of 0.758. The correlation between insight and depression
      is high in subjects with less duration of illness. CONCLUSION: Better insight was
      significantly correlated with lower mood. In addition, it suggests that poor
      insight may protect against depression in the early stages of recovery from
      schizophrenia. The correlation between insight and depression is high in subjects
      with less duration of illness.

PMID- 22661808
TI  - Domains and determinants of quality of life in schizophrenia and systemic lupus
      erythematosus.
AB  - BACKGROUND: The World Health Organization Quality of Life-Bref (WHOQOL-Bref)
      scale was designed to measure quality of life (QOL) in both medical and
      psychiatric illnesses. There have been a few studies to date that compare aspects
      of QOL in medical and psychiatric illnesses. AIM: The aim of the study was to
      compare QOL in patients with systemic lupus erythematosus (SLE), a chronic
      medical illness and schizophrenia, a chronic psychiatric disorder. MATERIALS AND
      METHODS: In a prospective design, 50 patients with SLE and 50 patients with
      schizophrenia were assessed on measures of QOL by using the WHOQOL-Bref scale,
      demographic factors, disease severity, and psychiatric comorbidity. RESULTS:
      There was a significant difference between the SLE group and the schizophrenia
      group on the social domain of the WHOQOL-Bref scale but not on other domains.
      Patients with SLE had lower scores, except on social domain. Disease severity
      correlated with scores on the physical domain and environmental domain in both
      illnesses. The presence of psychiatric comorbidity was associated with
      significantly lower QOL scores in SLE. The presence of insight was associated
      with nonsignificantly lower QOL scores in schizophrenia. There was a significant
      association between QOL scores and both income and religious belief system in
      SLE, while age and duration of illness correlated with QOL scores in
      schizophrenia. CONCLUSION: Although the QOLs in schizophrenia and SLE were
      comparable on all domains except the social domain, the factors that mediate QOL
      in both these illnesses are different.

PMID- 22661809
TI  - Rapid Antidepressant Response with Ketamine: Is it the Solution to Resistant
      Depression?
AB  - BACKGROUND: Treatment-resistant depression (TRD) is a relatively common
      condition, challenging the clinician. There is an urgent need to develop
      pharmacological treatments for TRD that exert rapid and sustained antidepressant
      effects. Ketamine induces a rapid antidepressant effect. AIMS: In India, very few
      studies have corroborated such findings, and the present study aimed to assess
      the effectiveness and sustainability of antidepressant effects of ketamine in
      subjects with TRD. MATERIALS AND METHODS: The present study was a single-center,
      prospective, 4-week, open-label, single-arm pilot study. Twenty-two subjects with
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major
      depression (treatment resistant) were recruited. After a 2-week drug-free period,
      subjects were given a single intravenous infusion of ketamine hydrochloride (0.5
      mg/kg) and were rated at baseline and at 40, 80, 110, and 230 min and 1, 2, 3, 4,
      7, and 14 days postinfusion. The main outcome measure was changes in scores on
      the 17-item Hamilton Depression Rating Scale (HDRS). Data were analyzed by using
      Freidman's analysis of variance and a post hoc test. RESULTS: The ketamine
      infusion was effective in reducing the HDRS scores, and the change remained
      significant from minute 80 to day 3 postinfusion at each time point. The change
      was not significant at any time after day 3. CONCLUSION: The real strength of
      this study rests in documenting the rapid, albeit short-lived, antidepressant
      effect of ketamine in TRD.

PMID- 22661810
TI  - A Study of Attitude and Knowledge of the Psychiatry Resident Doctors toward
      Clinician-Pharmaceutical Industry Interaction.
AB  - BACKGROUND: Pharmaceutical industry and clinicians are the two important
      stakeholders in the modern-day health care. However, concerns have been expressed
      about the lack of congruence between the goals of these two. AIMS: The current
      study aimed at exploring the knowledge and attitude of the psychiatry resident
      doctors toward the clinician-pharmaceutical industry interaction and also at
      exploring the knowledge of the residents about the new Medical Council of India
      guidelines on this issue. MATERIALS AND METHODS: The survey was conducted among
      psychiatry residents. Descriptive statistics with frequency distribution was
      carried out by using SPSS version 17.0. RESULTS: It had a good response rate of
      around 90%. The survey reveals the knowledge and attitude of the psychiatry
      residents toward the psychiatrist-pharmaceutical industry interaction.
      CONCLUSIONS: The survey provides understanding in knowledge and attitude of the
      psychiatry residents towards the psychiatrist-pharmaceutical industry
      interaction.

PMID- 22661811
TI  - A Comparative Study of Attitude of Mental Health Versus Nonmental Professionals
      toward Suicide.
AB  - BACKGROUND: Suicide is a major public health problem. Suicide can be prevented by
      understanding the disorder. Attitude plays a significant role in doing so. AIM:
      To assess the attitudes of mental health professionals and non-mental health
      professionals towards an act of suicide and to compare the two groups regarding
      their attitudes. MATERIALS AND METHODS: A semistructured questionnaire having
      yes/no type questions was administered to 30 mental health and 30 nonmental
      health professionals. A blind analysis of the data was done. STATISTICAL
      ANALYSIS: Comparative analysis using mean and standard deviation and analysis of
      variance was performed to rate significance in differences of responses to
      questions that rate attitudes. RESULTS: The results show a significant positive
      attitude of mental health professionals toward dealing with the patients who
      attempted suicide. DISCUSSION: Considering the magnitude of the problem, simple
      training and education of nonmental health professionals can change their
      attitude toward patients who attempt suicide, which in turn leads to an optimal
      management. CONCLUSION: The study shows that the mental health professionals are
      much more positive in their approach towards a patient of parasuicide.

PMID- 22661812
TI  - Disability in a Group of Long-stay Patients with Schizophrenia: Experience from a
      Mental Hospital.
AB  - BACKGROUND: Recovery from schizophrenia is a complex concept. Remission of
      symptoms of psychotic illnesses is not necessarily linked to better functioning.
      Among various causes of disability, mental illnesses account for 12.3% of the
      global burden of diseases. Long-term hospitalization has been recognized as
      counterproductive and a contributory factor of disability associated with
      schizophrenia. Under various circumstances, many persons with mental illness are
      brought to mental hospitals but the measures taken for their rehabilitation and
      follow-up care is insufficient. AIM: In the present study we tried to find out
      the level of psychopathology and the associated disability in a group of patients
      with schizophrenia who have been staying in a mental health institution for more
      than 5 years due to lack of proper caregivers in the society or in their home.
      MATERIALS AND METHODS: The study is conducted in a mental hospital of northeast
      India. Of the 40 patients staying for more than 5 years in the hospital, 28
      fulfilled the criteria for inclusion. The Brief Psychiatric Rating Scale and
      World Health Organization Disability Assessment Schedule II (WHO DASII) were used
      for those patients. Analytical statistical methods were used subsequently.
      RESULTS: Male patients were significantly older and had prolonged duration of
      stay. But the level of psychopathology did not differ significantly between male
      and female patients. Under WHODASII, understanding and communication problems are
      more prominent in both the groups. Of late, there are very few cases that
      required prolonged stay in the hospital. Many patients are fairly functional and
      are considered suitable for care outside hospital premises. CONCLUSION: Prolonged
      hospital stay is associated with more disability. Shorter hospital stays with
      proper family support is an ideal way to counteract this issue. However, due to
      the inadequate mandate in the Mental Health Act (MHA) 1987 and lack of other
      supportive facilities, patientsoften tend to languish in the hospital for longer
      duration, causing harm to the patients and draining scarce state resources. It is
      therefore necessary to revisit the MHA 1987 and provide adequate rehabilitative
      measures for the needy patients.

PMID- 22661813
TI  - Functional hallucinations in schizophrenia responding to adjunctive sodium
      valproate.
AB  - Functional hallucinations are a rare phenomenon, wherein hallucinations are
      triggered by a stimulus in the same modality, and co-occur with it. Although
      hallucinations in schizophrenia are normally treated using antipsychotics, not
      all patients respond to them. The following is the report of a patient with
      paranoid schizophrenia who experienced persistent functional hallucinations,
      triggered by the sound of machines in his factory, in the absence of other
      psychotic symptoms. These occurred despite adequate doses of risperidone, which
      had controlled his other symptoms. The addition of sodium valproate, titrated up
      to 1700 mg/day based on response and tolerability, resulted in a marked
      improvement in this phenomenon and enabled him to return to work. The
      implications and possible mechanisms of the patient's response are discussed.

PMID- 22661814
TI  - Management of panic anxiety with agoraphobia by using cognitive behavior therapy.
AB  - Panic disorder with agoraphobia is a psychological disorder. We are presenting a
      case report of male client, visted as out door patient in the counseling centre
      of National Institute of psychology. Client reported the symptoms such as
      palpitations, pounding heart, accelerated heart rate, sweating,
      trembling/shaking, feeling of choking, chest pain, discomfort, nausea, abdominal
      distress, feeling dizzy, lightheadedness, and fear of losing control when he is
      in the crowd. The signs and symptoms of a panic attack develop abruptly and
      usually reach their peak within 10 min. Most panic attacks end within 20 to 30
      min, and they rarely last more than an hour. The client was diagnosed, Panic
      Anxiety with Agoraphobia. Cognitive behaviour therapy was used for the treatment.
      After seven sessions, client's symptoms were diminished.

PMID- 22661816
TI  - Successful use of add - on topiramate for antipsychotic - induced weight gain.
AB  - Antipsychotic induced weight gain is the most common and distressing side effect.
      This also affects the compliance toward the treatment and hence the prognosis.
      Non - pharmacological interventions such as exercise and diet modifications alone
      might not be sufficient most of the times; also ensuring compliance toward this
      is difficult in patients with psychiatric illness. So, the role of weight -
      reducing drugs become important. In this case report, we describe the use of low 
      dose topiramate as a weight - reducing agent, in a patient with a bipolar
      affective disorder - mania with psychotic symptoms, who had significant
      risperidone - induced weight gain.

PMID- 22661815
TI  - Pseudocyesis Versus Delusion of Pregnancy: Differential Diagnoses to be Kept in
      Mind.
AB  - Pseudocyesis is a condition in which the patient has all signs and symptoms of
      pregnancy except for the confirmation of the presence of a fetus. The literature
      on delusions of pregnancy in schizophrenia is however scanty. We hereby present a
      case of delusion of pregnancy. The case highlights the possibility of delusion of
      pregnancy if a patient presents with features suggestive of pseudocyesis. The
      obstetricians being more familiar with pseudocyesis might tend to overlook the
      other possibility in such cases. This would be especially true if there are no
      associated clearcut psychotic features.

PMID- 22661817
TI  - Chronic mania: an underrecognized clinical entity.
AB  - Chronic mania (defined as the presence of manic symptoms for more than 2 years
      without remission) poses significant problems in diagnosis and management.
      Generally it denotes poor outcome, though contrary reports are available. We
      present a case of chronic mania and discuss the clinical features of chronic
      mania reported in the literature, which are useful in distinguishing chronic
      mania from acute mania.

PMID- 22661818
TI  - Psychosis in patients with systemic lupus erythematosus.
AB  - Neuropsychiatric manifestations in systemic lupus erythematosus (SLE) are common;
      however, psychosis per se is bit uncommon. They may be cognitive deficit, lupus
      headache, psychoses, seizures, peripheral neuropathy, and cerebrovascular events.
      Psychiatric symptoms in SLE can be functionally independent psychiatric
      disorders. It can be due to drugs (steroids) used for SLE or secondary to SLE
      because of its brain involvement, which is termed as neuropsychiatric systemic
      lupus erythematosus (NPSLE). No single clinical, laboratory, neuropsychological,
      and imaging test can be used to differentiate NPSLE from non-NPSLE patients with
      similar neuropsychiatric manifestations. Presently we are discussing about three
      cases of SLE with psychosis and which had different clinical presentation. The
      present reports also depict the approach to case differential diagnosis and
      management of the same.

PMID- 22661819
TI  - Munchausen syndrome as dermatitis simulata.
AB  - Psychiatric comorbidity is associated with many dermatological disorders. It may
      be the cause for skin problem or may be the effect of a skin problem as skin
      being a visual organ. A 28-year-old female presented with multiple red lesions on
      the skin with unusual morphology and was diagnosed as dermatitis simulata. She
      gave history of multiple episodes of similar illnesses with admissions in various
      hospitals and being evaluated and dropping off in between treatments. After
      detailed psychological evaluation, patient was diagnosed as case of Munchausen
      syndrome.

PMID- 22661820
TI  - The 'Holy Grail' and 'Poisoned Chalice' Effects of Antipsychotics on Oxidative
      Stress in Schizophrenia: Can 'Hormesis' Explain this Paradox?

PMID- 22661821
TI  - Psychotherapy - insights from bhagavad gita.
AB  - Spoken and written commentary on Bhagavad Gita, the distilled spiritual essence
      of Vedas and Upanishads, is aplenty. Mahatma Gandhi was quoted as saying that
      whenever he had a problem Bhagavad Gita offered an answer and the solution. For a
      student of psychology Bhagavad Gita offers a valuable case study for lessons in
      psychotherapy - resolution of conflict and successful resumption of action from a
      state of acute anxiety and guilt laden depression that precipitated inaction.
      This presentation makes a humble attempt to discuss the therapy process involved
      in Bhagavad Gita in which Lord Krishna helped the grief-stricken Arjuna through
      dialogue and discussion. The focus would be on the conflict and diagnosis of
      patient, the background setting of the situation, personality of patient,
      technique of therapy, underlying psychological concepts/ principles/theories, the
      Guru - Sishya concept, etc.

PMID- 22661822
TI  - Structural distributions from single-molecule measurements as a tool for
      molecular mechanics.
AB  - A mechanical view provides an attractive alternative for predicting the behavior
      of complex systems since it circumvents the resource-intensive requirements of
      atomistic models; however, it remains extremely challenging to characterize the
      mechanical responses of a system at the molecular level. Here, the structural
      distribution is proposed to be an effective means to extracting the molecular
      mechanical properties. End-to-end distance distributions for a series of short
      poly-L-proline peptides with the sequence P(n)CG(3)K-biotin (n = 8, 12, 15 and
      24) were used to experimentally illustrate this new approach. High-resolution
      single-molecule Forster-type resonance energy transfer (FRET) experiments were
      carried out and the conformation-resolving power was characterized and discussed
      in the context of the conventional constant-time binning procedure for FRET data
      analysis. It was shown that the commonly adopted theoretical polymer models
      including the worm-like chain, the freely jointed chain, and the self-avoiding
      chain-could not be distinguished by the averaged end-to-end distances, but could
      be ruled out using the molecular details gained by conformational distribution
      analysis because similar polymers of different sizes could respond to external
      forces differently. Specifically, by fitting the molecular conformational
      distribution to a semi-flexible polymer model, the effective persistence lengths
      for the series of short poly-L-proline peptides were found to be size-dependent
      with values of ~190 A, ~67 A, ~51 A, and ~76 A for n = 8, 12, 15, and 24,
      respectively. A comprehensive computational modeling was carried out to gain
      further insights for this surprising discovery. It was found that P(8) exists as
      the extended all-trans isomaer whereas P(12) and P(15) predominantly contained
      one proline residue in the cis conformation. P(24) exists as a mixture of one-cis
      (75%) and two-cis (25%) isomers where each isomer contributes to an
      experimentally resolvable conformational mode. This work demonstrates the
      resolving power of the distribution-based approach, and the capacity of
      integrating high-resolution single-molecule FRET experiments with molecular
      modeling to reveal detailed structural information about the conformation of
      molecules on the length scales relevant to the study of biological molecules.

PMID- 22661823
TI  - Look before you leap - individual variation in social vigilance shapes socio
      spatial group properties in an agent-based model.
AB  - Next to predator detection, primate vigilance also serves to keep track of
      relevant conspecifics. The degree of vigilance towards group members often
      reflects the dominance rank of an individual: subordinates pay attention to
      dominants. Although it has been suggested that subordinates' vigilance may result
      in spatial centrality of dominants, this has not been addressed in either
      empirical or modeling studies. Using agent-based models, we determined how social
      vigilance affects socio-spatial properties of primate groups. A basic model
      without social vigilance, where individuals avoid potential aggressors (avoidance
      model), was contrasted with two models that each additionally included a
      different type of social vigilance: a) monitoring a specific potential aggressor
      to remain informed on its whereabouts (monitoring model) or b) scanning the whole
      group to detect potential aggressors (scanning model). Adding monitoring or
      scanning behavior to the avoidance model reinforced spatial centrality of
      dominants, a pattern often observed in primates, and resulted in more spread out
      groups. Moreover, variation in scanning tendency alone was already sufficient to
      generate spatial centrality of dominants: frequently scanning subordinates could
      move further away from the group center than dominants, before losing sight of
      group members. In the monitoring model, two mechanisms caused decreased encounter
      frequencies among subordinates: a) increased inter-individual distances, and b)
      frequent monitoring of central dominants. In the scanning model, encounters among
      subordinates decreased due to increased inter-individual distances. This agent
      based model study provides a clear indication that individual variation in social
      vigilance may be an important structuring feature of primate social groups.

PMID- 22661825
TI  - The Ex Situ Comparison of Two Improved St. John's wort (Hypericum perforatum)
      Cultivars with an Iranian Wild Population.
AB  - This research is part of an ongoing selection and breeding effort to target
      Iranian genotypes of Hypericum perforatum with the potential to produce higher
      amounts of desired secondary metabolites and greater resistance to fungal
      pathogens. There is a significant interest in the development of such cultivars
      to supply materials to the local pharmaceutical industries. For this reason, two
      improved cultivars of H. perforatum ("Gold" and "Veperikon") were compared with a
      wild Iranian population (Ardabile population) under common garden conditions in
      Iran. Plants were cultivated from seed in a greenhouse and seedlings were
      transplanted after one month to the field plots. The statistical design of this
      study was a Randomized Complete Block Design with three replications. During the
      period of full flowering, selected phenological (number of days to flowering),
      morphological (plant height, mean leaf area, number of black glands/leaf) and
      chemical (hypericin and pseudohypericin content) characteristics were assessed.
      Our observations were that the "Veperikon" cultivar is very sensitive to soil
      borne diseases. All transplanted seedlings were infected by the plant pathogenic
      fungus Colletotrichum gloeosporioides, which caused necrosis of the whole plant.
      Both the "Gold" cultivar and plants from the wild population persisted despite
      mild infections with C. gloeosporioides and produced flowering shoots at both the
      first and second years after cultivation. The "Gold" cultivar was superior to the
      Ardabile population in terms of phenological and morphological characteristics.
      The average naphthodianthrone content (% dry weight of tissue) for the wild
      Iranian population was 0.04(+/-0.01)%, but for the "Gold" cultivar, 0.33(+/
      0.43)%. These data indicate that selection and directed cultivation of Iranian H.
      perforatum plants can result in plants with improved morphological, phenological
      and chemical characteristics.

PMID- 22661824
TI  - Evolution of self-organized division of labor in a response threshold model.
AB  - Division of labor in social insects is determinant to their ecological success.
      Recent models emphasize that division of labor is an emergent property of the
      interactions among nestmates obeying to simple behavioral rules. However, the
      role of evolution in shaping these rules has been largely neglected. Here, we
      investigate a model that integrates the perspectives of self-organization and
      evolution. Our point of departure is the response threshold model, where we allow
      thresholds to evolve. We ask whether the thresholds will evolve to a state where
      division of labor emerges in a form that fits the needs of the colony. We find
      that division of labor can indeed evolve through the evolutionary branching of
      thresholds, leading to workers that differ in their tendency to take on a given
      task. However, the conditions under which division of labor evolves depend on the
      strength of selection on the two fitness components considered: amount of work
      performed and on worker distribution over tasks. When selection is strongest on
      the amount of work performed, division of labor evolves if switching tasks is
      costly. When selection is strongest on worker distribution, division of labor is
      less likely to evolve. Furthermore, we show that a biased distribution (like 3:1)
      of workers over tasks is not easily achievable by a threshold mechanism, even
      under strong selection. Contrary to expectation, multiple matings of colony
      foundresses impede the evolution of specialization. Overall, our model sheds
      light on the importance of considering the interaction between specific
      mechanisms and ecological requirements to better understand the evolutionary
      scenarios that lead to division of labor in complex systems. ELECTRONIC
      SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00265
      012-1343-2) contains supplementary material, which is available to authorized
      users.

PMID- 22661826
TI  - Change and Stability in Active and Passive Social Influence Dynamics during
      Natural Drinking Events: A Longitudinal Measurement-Burst Study.
AB  - We examined the link between social norms and active social influences occurring
      during natural social drinking contexts. Across 4 yearly measurement-bursts,
      college students (N = 523) reported daily for 30-day periods on drinking norms,
      drinking offers, how many drinks they accepted, and personal drinking levels
      during social drinking events. In contexts where drinking norms were higher,
      students were more likely to both receive and comply with drinking offers. These
      acute social influences were highly stable throughout college, but affected men
      and women differently across time: Women received more drinking offers than men,
      especially at the beginning of college and when norms were higher, but men
      complied with more drinking offers per occasion. These effects were not
      attributable to between-person differences in social drinking motives or drinking
      levels, nor to within-person patterns of situation-selection. The present work
      suggests that context-specific drinking norms catalyze active social influence
      attempts, and further promote compliance drinking.

PMID- 22661827
TI  - Child Behavior Checklist Scores for School-Aged Children with Autism: Preliminary
      Evidence of Patterns Suggesting the Need for Referral.
AB  - The Child Behavior Checklist (CBCL) is a widely used questionnaire to assess
      behavioral and emotional problems. It is often used as a diagnostic screener, but
      autism spectrum disorders (ASD) are not included in the CBCL for school-aged
      children. This study investigated patterns of CBCL scores in 108 children with
      high-functioning ASD from two independent samples, and 67 IQ- and age-matched
      controls. Scores on the CBCL Thought and Social Problems scales significantly
      differentiated children with ASD from controls. Both independent ASD samples had
      the same pattern of elevations, with mean scores over two standard deviations
      above the mean for Social, Thought, and Attention Problems. The
      Withdrawn/Depressed scale was elevated to at least the borderline clinical range
      for half of the ASD sample. This pattern of elevations is consistent with two
      prior studies of the CBCL with school-aged children with ASD, and therefore may
      warrant follow-up assessment to rule out an ASD.

PMID- 22661828
TI  - Movement goals and feedback and feedforward control mechanisms in speech
      production.
AB  - Studies of speech motor control are described that support a theoretical
      framework in which fundamental control variables for phonemic movements are multi
      dimensional regions in auditory and somatosensory spaces. Auditory feedback is
      used to acquire and maintain auditory goals and in the development and function
      of feedback and feedforward control mechanisms. Several lines of evidence support
      the idea that speakers with more acute sensory discrimination acquire more
      distinct goal regions and therefore produce speech sounds with greater contrast.
      Feedback modification findings indicate that fluently produced sound sequences
      are encoded as feedforward commands, and feedback control serves to correct
      mismatches between expected and produced sensory consequences.

PMID- 22661829
TI  - Dietary algae and HIV/AIDS: proof of concept clinical data.
AB  - Dietary algae have been reported to decrease HIV viral fusion/entry and
      replication and increase immune response, suggesting that regular consumption of
      algae by people in Japan, Korea, and Chad could be an important factor in their
      relatively low HIV/AIDS rates. Five antiretroviral-naive people with HIV (three
      females, two males; five African Americans) living in Columbia SC participated in
      the phase I study of acute toxicity. Subjects were randomly assigned to 5 g day(
      1) brown seaweed (Undaria pinnatifida), Spirulina (Arthrospira platensis), or a
      combination of both. Endpoints included HIV viral load, complete blood count
      (CBC), metabolic and lipid panel, and quality of life questionnaire data. When no
      short-term toxicities were observed, six additional subjects (four females, two
      males; five African Americans, one Latina) were recruited to further evaluate
      short- and long-term toxicities (phase II). No adverse effects were observed for
      the 11 subjects in the phase I trial, and quality of life indicators improved at
      3 weeks. No significant changes were observed in CBC, metabolic or lipid panel
      analyses. CD4 cells (milliliters) and HIV-1 viral load remained stable over the
      first 3-month phase II study period. One subject continued in the study for 13
      months and had clinically significant improvement in CD4 (>100 cells mL(-1)) and
      decreased HIV viral load of 0.5 log(10). Our pilot data suggest that Undaria,
      Spirulina, and a combination of both were nontoxic and over time may improve
      clinical endpoints of HIV/AIDS.

PMID- 22661830
TI  - Adjunctive cognitive remediation for schizophrenia using yoga: an open, non
      randomized trial.
AB  - BACKGROUND: Yoga therapy (YT) improves cognitive function in healthy individuals,
      but its impact on cognitive function among persons with schizophrenia (SZ) has
      not been investigated.  AIMS: Evaluate adjunctive YT for cognitive domains
      impaired in SZ.  METHODS: Patients with SZ received YT or treatment as usual
      (TAU; n = 65, n = 23, respectively). Accuracy and speed for seven cognitive
      domains were assessed using a computerized neurocognitive battery (CNB), thus
      minimizing observer bias. Separately, YT was evaluated among patients with
      Bipolar I disorder (n = 40), Major Depressive Disorder (n = 37), and cardiology
      outpatients (n = 68). All patients also received routine pharmacotherapy.
      Patients were not randomized to YT or TAU.  RESULTS: Compared with the SZ/TAU
      group, the SZ/YT group showed significantly greater improvement with regard to
      measures of attention following corrections for multiple comparisons; the changes
      were more prominent among the men. In the other diagnostic groups, differing
      patterns of improvements were noted with small to medium effect sizes. 
      CONCLUSIONS: Our initial analyses suggest nominally significant improvement in
      cognitive function in schizophrenia with adjunctive therapies such as YT. The
      magnitude of the change varies by cognitive domain and may also vary by
      diagnostic group.

PMID- 22661832
TI  - Nourishing the tree of Ayurveda: Enriched with specialty!

PMID- 22661831
TI  - Smoking and its effect on scar healing.
AB  - Scar formation is influenced by several factors such as wound infection, tension,
      wound depth and anatomical localization. Hypertrophic scarring is often the
      result of an imbalance in the wound and scar healing process. The exact
      underlying pathophysiological mechanism remains unclear. Smoking has a higher
      risk of postoperative complications probably due to a diminished macrophage
      induction. Following our clinical impression that smokers without postoperative
      wound infections show esthetically better scars, we evaluated the scars after a
      reduction mammaplasty in smoking and nonsmoking patients in a prospective
      clinical trial. Between July 2006 and September 2007, 13 smokers and 30 non
      smokers with a reduction mammaplasty were included. They were recruited from
      Viecuri Medical Centre and Atrium Medical Centre in the Netherlands after written
      consent. Surgical data and data of the patients' condition were collected. Follow
      up for erythema values of the scars was done with a colorimeter (The Minolta CR
      300, Minolta Camera Co., Ltd., Osaka Japan) at 1, 3, 6 and 9 months
      postoperatively on four standardized postsurgical sites. ANOVA and Chi-square
      test were used for statistical analysis. In the smoking group, the scars were
      significantly less red compared to the nonsmoking group. No significant
      differences were found in BMI, resection weight and drain production between both
      groups. Although smoking is certainly not recommended as a preventive therapy to
      influence scar healing, this study confirms our assumption that smokers tend to
      have faster and less erythemateous scar healing to nonsmokers. Further research
      is needed to understand the mechanism of the effect of smoking on scars.

PMID- 22661833
TI  - Exploring progression of Ayurveda.

PMID- 22661834
TI  - Water purification prescribed in Ayurveda.
AB  - Authors present here water purifying methods for drinking purpose by employing
      few kinds of flowers, a traditional knowledge available in India from the
      classics of Ayurveda, the oldest system of medical practices. A simple method is
      designed to conduct a study for finding out the efficacy of the said method.

PMID- 22661835
TI  - Nisshesha rechaka pranayama offers benefits through brief intermittent hypoxia.
AB  - Hypoxia has been a frightening term for doctors and medical students because of
      the possibility of damage to cells, tissues and organs. However, we now know that
      brief, episodic hypoxia gives rise to several adaptive responses. These responses
      in general prepare the body for better tolerating such hypoxic episodes, and also
      offer protection against several other types of insults. Indeed, scientists at
      the erstwhile U.S.S.R. have developed what is known as 'hypoxia therapy' and
      reaped the benefits of brief intermittent hypoxia for the last several decades.
      In India, yogic treatment of various diseases is common. A lesser known but
      important variety of Pranayama is 'nisshesha rechaka', which may be described as
      breath holding at residual volume. Studies done at our centre have demonstrated
      that Nisshesha rechaka is the easiest way to produce brief, intermittent hypoxia.
      There is therefore reason to believe that Nisshesha rechaka pranayama may offer
      benefits through this mechanism.

PMID- 22661836
TI  - Basavarajeeyam: A historical perspective.
AB  - Basavarajeeyam is an important handbook for an Ayurvedic physician of Andhra
      region. It is a bilingual work and the content was presented in Sanskrit and
      Telugu languages. With regard to the place and date of Basavarajeeyam there is no
      common opinion among the present day scholars. Pt Govardhana Sharma Changani in
      his introduction to the Sanskrit version of Basavarajeeyam exposed a historical
      profile of Basavrajeeyam picturising him as Basava who was a staunch follower of
      Veerashaivism and a contemporary of king Bijjala (end of 12(th) cent. AD). The
      same statement is carried out in the works of Ayurvedic Itihasa written by
      Atredeva Vidyawalkan and Acharya Priyavrata Sharma. It appears that the
      historical evidence shown by these scholars is one sided and cannot stand any
      reason. Basavraju stated that he had started writing this work after a thorough
      study of many works such as Charaka, Nithyanatheeyam (1360 AD), Revenakalpam,
      Pujyapadiyam, Bahatam, Kashikhandam (1435 AD) etc. Basavraju has faithfully
      reproduced certain chapter of Vaidyachintamani, which is considered to be a work
      of 15(th) century. Basavraju not only mentioned Phirangiroga in the index of
      diseases described by him at the end of the book, but also indicated
      Phirangichekka (Madhusnuhi) in the management of Meharoga and Granthi. By this
      evidence Basavarajiyam should be considered as the work of post Bhavaprakasha
      period. Basavraju indicates in the Gulmaroga Chikitsa that Sankhadravaka should
      be administered in the dose of 'Ekanni'. The name Ekanni was given for a copper
      coin which came in to circulation of money during British India produced from
      Madras mint (1794 AD). Based on these internal evidences, it can be safely
      concluded that Basavraju belong to 18(th)century.

PMID- 22661837
TI  - A critical review of antiquity, authorship and contents of Haramekhala: A
      medieval work on humanities.
AB  - Ayurvedic science of life is one of the great contributions of India to the
      systems of health science. Apart from classical medical works, much information
      related to this Indian system is found elsewhere in other branches of science,
      such as Philosophy, Joutishya, Natya, Kavya, etc. Still much Ayurvedic
      information is clubbed in other compilations meant for general purpose. However,
      it is unfortunate that not all such works came into lime light; and still remain
      in the dark for many reasons. Haramekhala written by Mahuka is one such work,
      which contains Ayurvedic information along with various other themes, such as
      cosmetics. The author Mahuka lived in Dharanivaraha rajya of central India during
      Chapa Dynasty in 9(th)-10(th) century A.D. Haramekhala also known as Prayogamala
      comprises of five Paricchedas written in Prakrita language, later added by
      translations in Sanskrit called Chaya and foot notes in Sanskrit called Tika. The
      detail about this book is described in this article.

PMID- 22661838
TI  - Ritucharya: Answer to the lifestyle disorders.
AB  - Ritu, the season, classified by different features expresses different effects on
      the body as well as the environment. Ayurveda has depicted various rules and
      regimens (Charya), regarding diet and behavior to acclimatize seasonal
      enforcement easily without altering body homeostasis. The prime principle of
      Ayurvedic system of medicine is preventive aspect, can be achieved by the change
      in diet and practices in response to change in climatic condition. This is a very
      important aspect of preventive medicine as mentioned in Ayurvedic texts.
      Lifestyle disorders are very common in the present era, basically originating
      from lack of following seasonal regimens due to lack of concentration in seasonal
      characteristics. A firm scientific analysis is the base, which holds true even on
      date. In this review article, various regimens in diet and lifestyle as mentioned
      in the classics of Ayurveda and their importance on lifestyle disorders has been
      discussed.

PMID- 22661839
TI  - Study of Vaikalyakara Marma with special reference to Kurpara Marma.
AB  - This study was undertaken to study Kurpara Marma in relation to its Vaikalyakara
      effects when injured. The location of Kurpara Marma was found with the help of
      the description of Marma in Ayurvedic texts, dissection of the elbow joint, and
      with help of X-ray documentation. Total 80 patients having trauma to elbow joints
      due to various causes such as fall, road traffic accident, direct trauma on elbow
      joint, history of trauma a year back, and injury due to burn were included in
      this study. These patients were observed for 3 months for any changes in
      symptoms. In Sushruta Samhita, it was stated that an injury to the Kurpara Marma
      ends in Kuni (dangling of the hand), swelling, loss of power, restricted
      movements, and muscle wasting and associated symptoms like tingling sensation,
      heaviness, syncope, sweating, dizziness, and vomiting. After analysis of data,
      i.e., after analyzing the percentage of all symptoms on admission as well as
      after 3 months, it was found that all 80 patients, i.e., 100% had swelling and
      loss of muscle power. A total of 72 patients, i.e. 90% had dangling of hand on
      admission. After 3 months, 40 patients (50%) still remained with the dangling of
      hand. Seventy-two patients had restriction in flexion and extension deformity
      which still remained in 50% of patients. Hence, it was proved that Kurpara (elbow
      joint) is definitely a Vaikalyakara Marma. Disabilities like restriction of
      movements, swelling, and atrophy were remains of an injured elbow joint inspite
      of best surgical treatment.

PMID- 22661840
TI  - Clinical evaluation of Boswellia serrata (Shallaki) resin in the management of
      Sandhivata (osteoarthritis).
AB  - Sandhigata vata is described under Vatavyadhi in all Ayurvedic texts. Charaka was
      the first to describe separately "Sandhigata anila", but it was not included
      under 80 types of nanatmaja vatavyadhi. Osteoarthritis is the most common
      degenerative joint disease that begins asymptomatically in middle age with
      progressive symptoms in advancing age. Majority of people by the age 40 years may
      develop osteoarthritis, especially in weight bearing joints. Females are prone
      with 25% prevalence, whereas males have a prevalence of 16%. In the present
      study, 56 patients fulfilling the diagnostic criteria of Sandhigata vata, divided
      into two groups. Patients of first group were administered with 500 mg capsule of
      Shallaki, 6 g per day (in three divided doses) with lukewarm water (n=29) and the
      second group) capsule Shallaki as above along with local application of Shallaki
      ointment on the affected joints (n=23). After a course of therapy for 2 months,
      symptomatic improvement was observed in both the groups at various levels with
      promising results in the patients of first group.

PMID- 22661841
TI  - Effects of Ayurvedic treatment on 100 patients of chronic renal failure (other
      than diabetic nephropathy).
AB  - Chronic renal failure (CRF) refers to an irreversible deterioration in renal
      function, which develops over a period of years. This initially manifests only as
      a biochemical abnormality. CRF is considered when glomerular filtration rate
      (GFR) falls below 30 ml/min. The conventional approach of management includes
      dialysis and renal transplantation, which are not affordable by Indian population
      mainly due to economic reasons. Therefore, exploration of a safe and alternative
      therapy is needed, which proves to be helpful in reducing the requirement of
      dialysis and in postponing the renal transplantation. A clinical study of 100
      patients of CRF was conducted at OPD and IPD of PD Patel Ayurved Hospital,
      Nadiad. They were given Niruha basti of Punarnavadi kvatha daily with oral
      medicaments including Goksuradi guggulu, Rasayana churna, and Varunadi kvatha for
      1 month period. The patients of CRF, having diabetic nephropathy as a cause, were
      excluded since a separate study for diabetic nephropathy is being conducted.
      Results were analyzed statistically using the "t" test. The symptoms and signs,
      serum creatinine, blood urea, urine albumin level were reduced, which were found
      to be statistically highly significant on "t" test.

PMID- 22661842
TI  - A comparative study on Vamana Karma with Madanaphala and Krutavedhana in
      Ekakushtha (Psoriasis).
AB  - Vamana Karma (therapeutic emesis) is the best therapy for the elimination of
      vitiated Kapha Dosha. In the present clinical practice Madanaphala (Randia
      dumetorum) is mainly used for Vamana Karma. Apart from Madanaphala, five other
      drugs, and in total 355 formulations are described in Charaka Samhita; one of
      them is Krutavedhana (Luffa acutangula) kalpa (formulations). Krutavedhana is
      specially indicated in Gadha (compact) Dosha condition like Kushtha (skin
      diseases), Garavisha (slow poison), and so on, for Vamana Karma. The present
      study aimed to observe the effect on Vamana Karma and by that its effect on
      Ekakushtha (Psoriasis). Krutavedhana Beeja Churna (seed powder) was given with
      Madhu (honey) and Saindhava (rock salt) as Vamana Yoga (emetic formulation), to
      compare it with Madanaphala Pippali Churna (seed powder). After the Sansarjana
      Krama (special dietetic schedule), Panchatikta Ghrita (medicated ghee) was given
      as Shamana Sneha (pacifying oleation). An average dose of Krutavedhana was 5.9 g.
      Krutavedhana could produce a good number of Vega (bouts), Pittanta Lakshana (bile
      coming out at the end of Vamana), and Pravara Shuddhi (maximum cleansing) in a
      majority of patients. Madanaphala is the best among all Vamaka (emetic) drugs,
      but Krutavedhana showed a similar to higher effect on Vamana Karma in terms of
      Antiki, Maniki, Vaigiki, and LaingikiShuddhi (cleansing criteria). Vamana Karma
      by Krutavedhana showed better relief in Matsyashakalopamam (silvery scale), Kandu
      (itching), and Rukshataa (dryness), while Madanapahala showed better relief in
      Krishnaruna Varna (erythema). After completion of the Shamana (pacifying)
      treatment, both the groups showed nearly the same effect on Asvedanam (lack of
      perspiration), Matsyashakalopamam, Kandu, Rukshataa, Krishnaruna Varna, and
      Mahaavaastu (bigger lesion).

PMID- 22661843
TI  - A comparative clinical trial of Chincha kshara and Kadali kshara on Amlapitta.
AB  - A clinical trial was carried out on 30 patients of Amlapitta aged between 20 to
      35 years with complaints of Avipaka, hrit-kanthadaha, tikta-amlodgara, utklesa,
      udarasula, adhmana and aruchi, who were registered from OPD and IPD of Gopabandhu
      Ayurveda Mahavidyalaya, Puri. They were equally divided into three groups Chincha
      kshara, Kadali kshara and placebo (who were administered with fresh wheat powder)
      for 30 days in a dose of 500 mg thrice daily with water. Investigations was done
      in order to exclude upper gastrointestinal tract ulcer, carcinoma in stomach,
      cholecystitis, carcinoma gall bladder, and heart diseases. The clinical
      assessments were carried out on the 30(th) day by subjective and objective
      parameters and it was inferred that both Chincha kshara and Kadali kshara were
      effective and reduced the symptoms of amlapitta. Chincha kshara was found to be
      more effective than Kadali kshara. The study shows the effect of Chincha and
      Kadali kshara which led to cure in 4(40%) and 3(30%) patients respectively, and
      maximum improvement in 4(40%) and 5(50%) patients affected with amlapitta
      disease, respectively. No untoward effect was noticed due to administration of
      ksharas during the clinical trial period.

PMID- 22661844
TI  - A comparative study of Shvasahara Leha and Vasa Haritaki Avaleha in the
      management of Tamaka Shvasa (Bronchial Asthma).
AB  - Tamaka Shvasa is a type of Shvasa Roga associated with difficulty in breathing as
      a result of which the patient prefers to sit in bed to get relief from his
      discomfort. Movement of air through Pranavaha Srotas is hampered in this disease
      resulting in the cry of organ heading toward complete failure for want of air.
      Tamaka Shvasa is well known for its episodic and chronic course which comes under
      the life-threatening disease. It is analogous to bronchial asthma due to
      similarity in symptoms, pathogenesis, onset, causes, and precipitating factors.
      In this study, 40 patients of Tamaka Shvasa were registered and randomly divided
      into two groups, out of which 31 patients completed the treatment. In Group A,
      Shvasahara Leha (5 g twice a day) was given for 2 months, while in Group B Vasa
      Haritaki Avaleha (5 g twice a day) was given for 2 months and follow-up was done
      for one month in both groups. The effects of therapy in both groups were assessed
      by a specially prepared proforma. Diagnosis was done by adult asthma diagnosis
      questionnaire and differential diagnosis with COPD (Chronic obstructive pulmonary
      disease) was done by differential diagnosis questionnaire as both these
      conditions are overlapping. The results of the study indicate that the Vasa
      Haritaki Avaleha provided better relief than Shvasahara Leha in Tamaka Shvasa.

PMID- 22661845
TI  - A clinical study on the effect of Rishyagandha (Withania coagulans) in the
      management of Prameha (Type II Diabetes Mellitus).
AB  - The study was conducted with an objective of evaluating the role of Rishyagandha
      (Withania coagulans) powder in clinically diagnosed cases of Prameha. 53
      Registered cases were divided into 3 groups; Group A (Rishyagandha fruits
      powder), Group B (Oral Hypoglycaemic Agent i.e. OHA), and Group C (Rishyagandha
      fruits powder and OHA both). Statistically significant improvement was observed
      in objective and subjective parameters in all 3 groups after completion of the
      course of treatment. Based on the results, it has been concluded that,
      Rishyagandha fruits powder is an effective therapeutic regimen in the management
      of uncomplicated cases of Prameha.

PMID- 22661846
TI  - Fundamental approach in the management of Drava Bahula Amlapitta with Bhringaraja
      (Eclipta alba).
AB  - The disease Amlapitta has been selected for the clinical trials because it
      presents two type of manifestations depending upon the involvement of Agni
      (Ushnagunadhikya) and Jala (Dravagunadhikya) Mahabhuta. The present research work
      was focused at Drava Guna, with an aim to assess the efficacy of a drug with
      quality of Ruksha and Ushna predominance like Bhringaraja in treating Amlapitta
      with Pitta Drava Guna Vriddhi. Randomized open clinical trials were conducted on
      22 patients of Amlapitta who were screened on the basis of clinical findings and
      allocated in to two groups. The criteria for selection were the signs and
      symptoms of Dravagunadhikya Amlapitta, irrespective of sex, religion, etc. Group
      A consisting of 15 cases received the trial drug Bhringaraja tablet (4 Tab. two
      times, 1 tablet=500 mg) and 7 cases in Group B received rice powder tablet as a
      placebo (4 Tab. two times, 1 tablet=500 mg) for 4 weeks. Special scoring pattern
      was adopted for the assessment of Amlapitta. Routine pathological tests such as
      blood, urine, stool, etc. were also carried out. In Group A, 55.33% patients
      showed marked improvement, whereas moderate improvement was observed in 26.67%
      patients. Complete cure was found in 06.67% of the patients and mild improvement
      in the chief complaints was observed in 13.33% patients. All the selected
      symptoms showed statistically significant results (P<0.01) except the Vidbheda in
      treated Group A, while in Group B, all symptoms showed statistically
      insignificant results except the Utklesha and Amlodgara. Total effect of the
      therapy showed statistically significant effect of the test drug. These results
      support the hypothesis.

PMID- 22661847
TI  - An open clinical trial to analyze Samyak Snigdha Lakshana of Shodhananga
      Snehapana with Mahatikthakam Ghritam in Psoriasis.
AB  - An open clinical trial was conducted in Govt. Ayurveda College Hospital,
      Thiruvananthapuram, Department of Kayachikitsa and Panchakarma. As there is no
      work done on the Samyak Snigdha Lakshana (SSL), this study was undertaken to work
      on the different aspects of Samyak Snigdha Lakshana. To minimize variables,
      subjects suffering with psoriasis and same Ghritam were selected on the basis of
      strict inclusion and exclusion criteria. Shodhananga Abhyantara Snehapana was
      advised before Vamana and Virechana. Samyak Snigdha Lakshanas which are described
      in all texts are different in milieu. Shodhananga Snehapana with Mahatiktakam
      Ghritam was given according to Koshta and Agni in 30 subjects. Samyak Snigdha
      Lakshanas were assessed using a special scoring pattern and the biochemical
      parameters were observed in all subjects. Statistical analysis using paired't'
      test were done. In all patients Vatanulomana, Diptagni, Snehodvega, Klama and
      Adhastat Sneha Darshanam were seen; whereas Angalaghava and Twak Snigdhata were
      noted in less percentage of persons. The onset of various Samyak Snigdha
      Lakshanas occurs in sequence. There are changes in some biochemical parameters
      like serum cholesterol, Serum glutamic-oxaloacetic transaminase (SGOT) and fat
      globules in stool after Snehapana. Shodhananga Snehapana with Mahatikthakam
      Ghritam decrease features of psoriasis up to some extent. More in depth studies
      are required to evaluate their importance and for their application in modern
      medical practice.

PMID- 22661848
TI  - Clinical efficacy of Shilajatu (Asphaltum) processed with Agnimantha
      (Clerodendrum phlomidis Linn.) in Sthaulya (obesity).
AB  - Obesity is defined as the condition in which excessive amount of fat is
      accumulated in the body. Classical Ayurvedic texts describe eight types of
      despicable designated as 'Nindita purusha' including atisthaulya. Corpulent
      people are characterized by short in longevity, slow movement, difficult to
      indulge in sex, weak, emission of bad body odor, profuse perspiration, excessive
      hunger and excessive thirst. Sixty to seventy percent of cardiac patients die of
      obesity and contribute to develop coronary artery disease, diabetes mellitus,
      hypertension, hyperlipidaemia. In the present study, 66 patients of obesity were
      treated with Shilajatu processed with Agnimantha. After complition of therapy,
      5.09 +/- 0.24 kg and 2.06 +/- 0.10 kg/m(2) reduction of body weight and body mass
      index, respectively were noted. The result was found to be statistically highly
      significant (P<0.001). No adverse effects were observed in any of the treated
      patients.

PMID- 22661849
TI  - Effect of Ayurvedic herbs on control of plaque and gingivitis: A randomized
      controlled trial.
AB  - Ayurveda had mentioned various procedures for maintaining oral hygiene. These
      include procedures like gandusha, kavala, dantadhavana, and jivha lekhana
      (cleaning tongue). Various plants have been mentioned in Ayurveda for
      dantakashta. Various Ayurvedic dental formulations are available in market in the
      form of powders, paste, etc. Present study was conducted for evaluating the
      effect of one of such Ayurvedic toothpowder named UDM, in controlling plaque and
      reducing gum inflammation in patients of moderate gingivitis. Scaling, root
      planning, and polishing were done for all the patients participating in the
      study. Oral hygiene instructions were given that included brushing twice/day with
      assigned tooth powder using BASS method for tooth brushing and also massage over
      gum tissue with finger. All the patients were recalled after 15 days. Scores of
      plaque index and gingival index was recorded on day 1 and day 15 of treatment.
      Total of 15 patients were recruited in each group. The mean reduction in gingival
      index was 1.15 (P<0.05) and 1.26 (P<0.05) in positive control and UDM treatment
      groups, respectively. However, the mean reduction in plaque indices were found to
      be 2.03 (P<0.05) and 2.16 (P<0.05) in positive control and UDM groups,
      respectively. No significant difference was seen in both the parameters between
      the two groups.

PMID- 22661850
TI  - A comparative study of Vamana and Virechana Karma in the management of Sthula
      Pramehi w.s.r. to Type-2 diabetes.
AB  - In the present study, Vamana and Virechana along with palliative treatment was
      given to patients of Sthula Prameha (Diabetes mellitus or DM). An attempt was
      made to compare and evaluate the role of Shodhana therapy (Vamana and Virechana).
      Total 47 patients of Sthula Pramehi were registered in this study, out of which
      38 completed the treatment. The patients were divided into two groups, viz.
      Vamana with Shamana (Group A) and Virechana with Shamana (Group B). Eighteen
      patients completed the treatment in Group A and 20 in Group B. Neem giloy satva
      capsule was used as Shamana drug at a dose of 500 mg twice daily after meals for
      30 days in both the groups. The efficacy of therapy was assessed based on relief
      in cardinal signs and symptoms and blood sugar, lipid profile and other
      biochemical parameters etc. The results showed that the Vamana provided better
      relief in signs and symptoms as well as on fasting blood sugar (FBS) and
      postprandial blood sugar (PPBS) in comparison to Virechana.

PMID- 22661851
TI  - A clinical study on the role of Akshi Tarpana with Jeevantyadi Ghrita in Timira
      (Myopia).
AB  - Myopia is a major public health problem pertaining to eye that entails
      substantial societal, personal, educational, and economical impact. Various
      surveys in India have found the prevalence of myopia ranging from 6.9% to 19.7%.
      Myopia progression is irreversible and methods for the correction of myopia are
      not without complications. Myopia closely resembles Timira involving first and
      second Patala in terms of symptoms, anatomical structures involved, and the
      pathogenesis of the disease. The study is aimed at evaluating the efficacy of the
      Akshi-Tarpana procedure with Jeevantyadi Ghrita in fresh and old myopes. A total
      of 54 patients (108 eyes) having myopia >=-6 D were registered for the study and
      divided into two groups (Group A, Akshi-Tarpana with Jeevantyadi Ghrita, and
      Group B, Akshi-Tarpana with plain Go Ghrita), by stratified sampling. The
      procedure was done in 5 sittings of 5 days each with an equal interval of 5 days
      between each sitting. A total of 22 patients in Group A and 18 in Group B
      completed the treatment. Obtained data were statistically analyzed using a t-test
      and the study reveals that objectively, 09.30% and 05.55% eyes were cured, 16.28%
      and 02.78% markedly improved, and 34.88% and 11.11% moderately improved in Group
      A and B, respectively.

PMID- 22661852
TI  - Application of Satkaryavada based on theory of Karya-Karana Vada.
AB  - Cikitsa in Ayurveda is based on Karya-Karana Siddhanta. Satkaryavada is an
      independent view of Samkhyas regarding Karya-Karana. According to this principle,
      the Karya is present in Karana in subtle form before its manifestation. All the
      Karyas are possible only by the Sat Karana (existent cause). On this ground a
      hypothesis has been formulated and applied. The hypothesis was that since Karana
      is present in a drug it will perform the Karma. The clinical study was planned to
      study the Anulomana Karma of Haritaki in patients of Anaha. The drug was used in
      38 patients. These were divided into two groups. In group "A" 26 patients were
      provided with haritaki tablet, while in group "B" 12 patients were provided with
      placebo tablets. In group "A" 7.69% of patients got complete relief, followed by
      38.46% patients who got marked relief; 42.31% of patients got moderate relief,
      while 11.54% patients got mild relief. Group A showed highly significant results
      in comparison to group B.

PMID- 22661853
TI  - Identification of fruits of Tribulus terrestris Linn. and Pedalium murex Linn.: A
      pharmacognostical approach.
AB  - Gokshura is a well-known Ayurvedic drug that is used in many preparations.
      Botonically it is identified as Tribulus terrestris Linn., especially the roots
      and fruits of the plant. But instead the fruits of another plant Pedalium murex
      Linn. are commonly used and the drug is frequently substituted. Pharmacognostical
      study has been carried out to identify the distinguishing features, both
      morphological and microscopic, of the fruits of Tribulus terrestris Linn. and
      Pedalium murex Linn. This knowledge should help reduce the problem of
      substitution of the genuine drug.

PMID- 22661854
TI  - Study on Bhasma Kalpana with special reference to the preparation of Kasisa
      Bhasma.
AB  - Bhasma means ash but according to Ayurveda, Bhasma means conversion of a metal
      into a form which is irreversible in the sense that one cannot derive the metal
      back from it again (Apunarbhava). It should be so light so that it must float on
      the surface of water after sprinkling, called Varitara. Its particle should be so
      small that it can enter in to the creases of fingers called Rekha-purnatva. The
      preparative procedure of Bhasma is a bit complicated. Many texts are available
      regarding the identification, acceptable qualities of metals and minerals, their
      purification, uses and method of preparation of their Bhasma. But in many texts,
      the method of Bhasma preparation of some metals and minerals is mentioned very
      briefly, i.e. their references are available in Sutrarupa. This leads to many
      practical difficulties in the preparation of Bhasma. Kasisa Bhasma is one of
      them. The present work was aimed to study the basic concept of Bhasma Kalpana by
      means preparing Kasisa Bhasma. This study suggests some modifications and ways
      for standardization of Bhasma procedure.

PMID- 22661855
TI  - Standardization of Shirishavaleha with reference to physico-chemical
      characteristics.
AB  - Ten batches of Shirishavaleha were prepared by using Twak (Bark) and Sara
      (Heartwood) of Shirisha [Albizzia lebbeck Benth]. The adopted formulation was
      based on Shirisharishta of Bhaishajya Ratnavali. Though Shirisharishta has
      significant therapeutic effect in cases of Tamaka swasa, etc.; it has few
      difficulties during the pharmaceutical procedure like consuming long time,
      climatic influences etc. Considering these inconveniencies, the formulation
      composition has been converted in to Shirishavaleha. Avaleha has been prepared by
      using Twak and Sara of Shirisha. No significant differences were found in
      pharmaceutical aspects of both the samples of Shirishavaleha and the current
      method of preparation can be considered as standard. Attempts were also made to
      develop analytical profile of avaleha, which were almost similar in both the
      samples, except showing more Rf values in High Performance Thin Layer
      Chromatography profile of Sara group.

PMID- 22661856
TI  - Standard manufacturing procedure of Rajata Bhasma.
AB  - Rasa Shastra is a branch of Ayurveda which deals with the processing of minerals
      and metals having therapeutic importance. Rajata comes under the group of metals
      having high therapeutic value. Minerals and metals are mostly used in the form of
      Bhasma. During the medieval period Rasacharyas extensively worked and developed a
      number of processing methods for a single drug. They all are standard
      manufacturing procedures (SMP) which ensure the quality, safety, efficacy and
      reproducibility of the product. Earlier Ayurvedic physicians were producing
      medicines by themselves according to their need. Now a day, due to
      commercialization of Ayurvedic medicines and ignorance of classical methods,
      quality of drugs has deteriorated. Presently, the demand of Ayurvedic drugs in
      the global market is increasing day by day. Hence it is the need of time to
      develop SMP for Ayurvedic products for global acceptability. This paper aims at
      providing SMP for the manufacture of Rajata Bhasma and also attempts to study the
      effect of Shodhana process on Rajata. Rajata was obtained from the local market
      of Varanasi. Rajata Bhasma was prepared and it was observed that during the
      preparation of Rajata Bhasma, use of Muffle Furnace instead of conventional Puta
      is more advantageous due to better temperature control. Use of mercury and
      sulphur together acts as best medium in the preparation of Rajata Bhasma.

PMID- 22661857
TI  - Physico-chemical analysis of a Herbo-mineral compound Mehamudgara vati - A pilot
      study.
AB  - Efforts have been made to lay down analytical standards for Mehamudgara vati
      (MMV), which were not found reported till date. Weight variation showed that 90%
      tablets of MV manufactured in the Gujarat Ayurved University Pharmacy were within
      acceptable range (323 mg +/- 10%), pH 4.58, and disintegration time 17 min,
      whereas hardness was 1.25 kg/cm(2). Loss on drying was found to be 9.3% w/w, acid
      insoluble ash was 0.9 %w/w, water soluble extract was 24.06% w/w and methanol
      soluble extract 14.1% w/w. Determination of iron as Fe(2)O(3) was done as Lauha
      bhasma being the major ingredient of MMV. The result showed that iron content was
      reduced in the formulation (28.67%) as compared to that in Lauha bhasma (61.19%).
      In TLC, 5 spots each at 254 nm and 366 nm were found.

PMID- 22661858
TI  - Antiobesity effect of Stellaria media against drug induced obesity in Swiss
      albino mice.
AB  - The whole plant of Stellaria media (family: Caryophyllaceae) has been tested for
      its antiobesity activity by using progesterone-induced obesity model in female
      albino mice. The effect of S. media on food consumption pattern, change in body
      weight, thermogenesis, lipid metabolism, and histology of fat pad. were examined.
      Methanolic and alcoholic extracts of the S. media were used in the study.
      Methanolic extract of S. media (MESM) have prevented the increase in body weight,
      adipose tissue weight and size, and upturned obesity and associated
      complications. MESM has also shown promising effects compared with alcoholic
      extract of S. media may be because of its multiple mechanisms. These findings
      suggest that antiobesity activity produced by MESM is because of its anorexic
      property mediated by saponin and flavonoid and partly of by its beta-sitosterol
      content. beta-Sitosterol in the plant extract was confirmed by thin-layer
      chromatography study. beta-sitosterol is plant sterol having structural
      similarity with dietary fat which do the physical competition in the
      gastrointestinal tract and reduces fat absorption. Before carrying in vivo
      activity detail pharmacognostic and phytochemical analysis of the extracts was
      carried out. The plant has shown the presence of saponin, flavonoids, steroids
      and triterpenoids, glycosides, and anthocynidine. By this study, it can be
      concluded that, MESM is beneficial in suppression of obesity induced by
      progesterone.

PMID- 22661859
TI  - Antimicrobial and antifungal activities of Cordia dichotoma (Forster F.) bark
      extracts.
AB  - Cordia dichotoma Forst.f. bark, identified as botanical source of Shlesmataka in
      Ayurvedic pharmacopoeias. Present study was carried out with an objective to
      investigate the antibacterial and antifungal potentials of Cordia dichotoma bark.
      Antibacterial activity of methanol and butanol extracts of the bark was carried
      out against two gram negative bacteria (Escherichia coli, and Pseudomonas
      aeruginosa) and two Gram positive bacteria (St. pyogenes and Staphylococcus
      aureus). The antifungal activity of the extracts was carried out against three
      common pathogenic fungi (Aspergillus niger, A.clavatus, and Candida albicans).
      Zone of inhibition of extracts was compared with that of different standards like
      Amplicilline, Ciprofloxacin, Norfloxacin and Chloramphenicol for antibacterial
      activity and Nystain and Greseofulvin for antifungal activity. The extracts
      showed remarkable inhibition of zone of bacterial growth and fungal growth and
      the results obtained were comparable with that of standards drugs against the
      organisms tested. The activity of extracts increased linearly with increase in
      concentration of extract (mg/ml). The results showed the antibacterial and
      antifungal activity against the organisms tested.

PMID- 22661860
TI  - Anti-anxiety and anti-depressant activities of Sarasvata choorna in experimental
      animals.
AB  - The present study was undertaken to evaluate the anxiolytic and anti-depressant
      activity of Sarasvata choorna. The anxiolytic activity was evaluated in elevated
      plus maze (EPM) and the anti-depressant activity was evaluated in forced swimming
      test (FST). The efficacy of Sarasvata choorna was compared with the standard anti
      anxiety (diazepam 2 mg/kg) and anti-depressant (imipramine - 5 mg/kg) drugs. It
      was observed that Sarasvata choorna at the dose of 390 mg/kg is as effective as
      standard drugs used in anti-anxiety and anti-depressant activities in mice by
      increasing time spent in open arm and entries to open arm in EPM model and
      increasing immobility time in FST model respectively. Hence it can be concluded
      that Sarasvata choorna may be used as a potent therapeutic agent in treating
      anxiety and depressive disorders.

PMID- 22661861
TI  - "Ayurpathy" - The pharmaceuticalization of Ayurveda.

PMID- 22661863
TI  - Personnel communications.

PMID- 22661862
TI  - Mysore Tridosha scale.

PMID- 22661864
TI  - Editor's note--About this supplement.

PMID- 22661865
TI  - Trends in scale and structure of Korea's health expenditure over last three
      decades (1980-2009): financing, functions and providers.
AB  - This paper introduces statistics related to the size and composition of Korea's
      total health expenditure. The figures produced were tailored to the OECD's system
      of health accounts. Korea's total health expenditure in 2009 was estimated at
      73.7 trillion won (US$ 57.7 billion). The annual per capita health expenditure
      was equivalent to US$ PPP 1,879. Korea's total health expenditure as a share of
      gross domestic product was 6.9% in 2009, far below the OECD average of 9.5%.
      Korea's public financing share of total health expenditure increased rapidly from
      less than 50% before 2000 to 58.2% in 2009. However, despite this growth, Korea's
      share remained the fourth lowest among OECD countries that had an average public
      share of 71.5%. Inpatient, outpatient, and pharmaceutical care accounted for
      32.1%, 33.0%, and 23.7% of current health expenditure in 2009, respectively. A
      total of 41.1% of current health expenditure went to hospitals, 28.1% to
      providers of ambulatory healthcare (15.9% on doctor's clinics), and 17.9% to
      pharmacies. More investment in the translation of national health account data
      into policy-relevant information is suggested for future progress.

PMID- 22661866
TI  - Sustainability of Korean National Health Insurance.
AB  - Korean National Health Insurance (NHI) was established during only 12 yr from its
      inception (1977-1989), providing universal medical coverage to the entire nation
      and making a huge contribution to medical security. However, the program now
      faces many challenges in terms of sustainability. The low birth rates, aging
      population, low economic growth, and escalating demands for welfare, as well as
      unification issues, all add pressure to the sustainability of NHI. The old
      paradigm of low contribution--low benefits coverage--low NHI's fee schedule needs
      to be replaced by a new paradigm of proper contribution--adequate benefit
      coverage--fair NHI's fee schedule. This new paradigm will require reform of NHI's
      operating system, funding, and spending.

PMID- 22661867
TI  - Forecasting the future reimbursement system of Korean National Health Insurance:
      a contemplation focusing on global budget and Neo-KDRG-based payment systems.
AB  - With the adoption of national health insurance in 1977, Korea has been utilizing
      fee-for-service payment with contract-based healthcare reimbursement system in
      2000. Under the system, fee-for-service reimbursement has been accused of
      augmenting national healthcare expenditure by excessively increasing service
      volume. The researcher examined in this paper two major alternatives including
      diagnosis related group-based payment and global budget to contemplate the future
      of reimbursement system of Korean national health insurance. Various literature
      and preceding studies on pilot project and actual implementation of Neo-KDRG were
      reviewed. As a result, DRG-based payment was effective for healthcare cost
      control but low in administrative efficiency. Global budget may be adequate for
      cost control and improving the quality of healthcare and administrative
      efficiency. However, many healthcare providers disagree that excess care arising
      from fee-for-service payment alone has led to financial deterioration of national
      health insurance and healthcare institutions should take responsibility with
      global budget payment as an appropriate solution. Dissimilar payment systems may
      be applied to different types of institutions to reflect their unique attributes,
      and this process can be achieved step-by-step. Developing public sphere among the
      stakeholders and striving for consensus shall be kept as collateral to attain the
      desirable reimbursement system in the future.

PMID- 22661868
TI  - Light and shadows of the Korean healthcare system.
AB  - This article reviewed achievements and challenges of the National Health
      Insurance of the Republic of Korea and shared thoughts on its future directions.
      Starting with large workplaces of 500 or more employees in 1977, Korea's National
      Health Insurance successfully achieved universal coverage within just 12 yr in
      1989. This amazing pace of growth was possible due to a positive combination of
      strong political will and rapid economic growth. Key features of Korea's
      experience in achieving universal coverage include 1) gradual expansion of
      coverage, 2) careful consideration to maintain sound insurance finances, and 3)
      introducing multiple health insurance societies (multiple payer system) at the
      initial stage. Introduction of the health insurance has dramatically improved
      Korea's health indicators and has fueled the rapid growth of basic medical
      infrastructure including medical institutions and professionals. On the other
      hand, the successful expansion was not free from side-effects. Although coverage
      has gradually expanded, benefits are still relatively low. The current situation
      warrants concern because coverage expansion is driven by welfare populism
      asserted by irresponsible political slogans and lacks a social consensus on basic
      principles and philosophy regarding the expansion. Concentration of patients to a
      few large prestigious hospitals as well as the inefficiencies resulting from a
      colossal single-payer system should also be pointed out.

PMID- 22661870
TI  - Role of healthcare in Korean long-term care insurance.
AB  - With the rapid aging of the population, Korea introduced public long-term care
      insurance for older people in 2008. The long-term care insurance was designed as
      a separate scheme from the national health insurance, with eligibility
      qualifications and the certification process based on functional disability,
      benefits and coverage of community-based and institutional care, and a financing
      structure through multi-party contributions. Delivering appropriate health
      services to long-term care beneficiaries who manifest a high prevalence of
      comorbid chronic conditions with rising healthcare costs, however, presents a
      particular challenge. The lack of coordination between the health and long-term
      care sectors, limited consideration of physicians' assessments in the
      certification process, inadequate provision of health services in long-term care
      facilities, and overlapping and inefficient use of care resources act as barriers
      to providing comprehensive healthcare for older beneficiaries. Through active
      participation in the long-term care system, health professionals can help older
      patients navigate through the complex long-term care terrain to obtain quality
      healthcare.

PMID- 22661869
TI  - Health inequalities policy in Korea: current status and future challenges.
AB  - In recent years, health inequalities have become an important public health
      concern and the subject of both research and policy attention in Korea.
      Government reports, as well as many epidemiological studies, have provided
      evidence that a wide range of health outcomes and health-related behaviors are
      socioeconomically patterned, and that the magnitude of health inequalities is
      even increasing. However, except for the revised Health Plan 2010 targets for
      health equity, few government policies have explicitly addressed health
      inequalities. Although a number of economic and social policies may have had an
      impact on health inequalities, such impact has scarcely been evaluated. In this
      review, we describe the current status of research and policy on health
      inequalities in Korea. We also suggest future challenges of approaches and
      policies to reduce health inequalities and highlight the active and intensive
      engagement of many policy sectors and good evidence for interventions that will
      make meaningful reduction of health inequalities possible.

PMID- 22661871
TI  - Current situation and issue of Industrial Accident Compensation insurance.
AB  - Industrial Accident Compensation Insurance (IACI) has a history of about 50 yr,
      and is the oldest social insurance system in Korea. After more than 20 times of
      revision improvements in benefits, its contents and claim systems have been
      upgraded. It became the protector of injured workers and their families, and at
      the same time became the system which could cope with both financial burden of
      employers and their responsibilities. However, there are some issues to be
      reformed to upgrade the IACI: 1) the problems in the approval system of
      occupational diseases, 2) quality improvement of workers' compensation medical
      care, 3) vocational rehabilitation and return to work, 4) workers' compensation
      premiums and out-of-pocket money of injured workers, 5) issues in application of
      IACI. Growth of IACI cannot be achieved by an effort of an individual. Efforts by
      workers, owners, and government, in addition to physicians and welfare
      professionals toward the same goal are required for the next level improvement of
      IACI.

PMID- 22661872
TI  - Development and implementation of clinical practice guidelines: current status in
      Korea.
AB  - Documentation of unexplained geographic variations in medical practices and use
      of inappropriate interventions has led to the proliferation of clinical practice
      guidelines. With increased enthusiasm for guidelines, evidence exists that
      clinical practice guidelines often influence clinical practices or health
      outcomes. Their successful implementation may improve the quality of care by
      decreasing in appropriate variation and expediting the application of effective
      advances to healthcare practices. In Korea, physicians and healthcare
      professionals have begun to take interests in clinical practice guidelines.
      Currently, over 50 practice guidelines have been developed through professional
      academic organizations or via other routes; however, the quality of the
      guidelines is unsatisfactory, implementation in clinical settings is incomplete,
      and there is insufficient infrastructure to develop clinical practice guidelines.
      Korea must develop policies and invest resources to enhance the development and
      implementation of clinical practice guidelines.

PMID- 22661873
TI  - Establishment, present condition, and developmental direction of the new Korean
      healthcare accreditation system.
AB  - On July 23rd, 2010 a revised medical law (Article 58) was passed to change
      existing evaluation system of medical institutions to an accreditation system.
      The new healthcare accreditation system was introduced to encourage medical
      institutions to work voluntarily and continuously to improve patient safety and
      medical service quality. Changes regarding the healthcare accreditation system
      included the establishment of an accreditation agency, the voluntary
      participation of medical institutions, accreditation standards centering on the
      treatment process and patient safety, tracing methodology, and the announcement
      of comprehensive results concerning accreditation. Despite varying views on the
      healthcare accreditation system, including some that are critical, it is
      meaningful that the voluntary nature of the system acknowledges that the medical
      institutions must be active agents in improving medical service quality.
      Healthcare quality is not improved instantaneously, but instead gradually through
      continuous communication within the clinical field. For this accreditation system
      to be successful, followings are essential: the accreditation agency becomes
      financially independent and is managed efficiently, the autonomy and regulation
      surrounding the system are balanced, the professionalism of the system is
      ensured, and the medical field plays an active role in the operation of the
      system.

PMID- 22661874
TI  - Development of a research-based hospital model in Korea.
AB  - Noting the increasing public attention on healthcare, Korean society has shown
      greater attention to the significance of the health technology (HT) development.
      In order to promote HT competitiveness, the role of research-based hospitals
      (RBHs), in producing new ideas as well as utilizing final outcomes, has grown
      increasingly significant. Despite high quality healthcare professionals, state-of
      the-art equipment, and well-developed information technology, few hospitals in
      Korea are successful leaders in HT development. In order to understand HT
      research and development (R&D) programs in Korea as well as hospital-based R&D
      investment performance, this paper has analyzed a recent three-year R&D
      investment of the Korean government. In addition, a survey on how to promote RBHs
      in Korea has been proceeded through adopting the Delphi method. Several model
      cases of RBHs abroad have also been studied to understand key success factors in
      formulating a development model of RBHs in Korea. This paper proposes suggestions
      for the promotion of RBHs in Korea: systematic reform related to the hospitals,
      reinforcement of the infrastructure of the hospitals, empowering human resources
      and policy framework to support the hospitals.

PMID- 22661875
TI  - National screening program for transitional ages in Korea: a new screening for
      strengthening primary prevention and follow-up care.
AB  - Screening can effectively reduce mortality and morbidity in some diseases. In
      Korea, a practical national screening program for chronic disease was launched in
      1995 and several problems were discussed. The program focused primarily on
      disease detection without follow-up care. In addition, the test items were
      uniform regardless of subject's age, sex, or risk factors; and people with low
      socioeconomic status were excluded. To improve the quality of program, a new
      national screening program called the "National Screening Program for
      Transitional Ages (NSPTA)" was initiated in 2007. It targeted two age groups,
      ages 40 and 66, because these ages are important transition periods in one's
      lifecycle. Follow-up care and education for lifestyle modification has been
      intensified; screening tests for mental health problems and osteoporosis have
      been introduced. The pool of eligible participants has been expanded to include
      people supported by Medicaid. This review aimed to describe the contents,
      process, and characteristics of the NSPTA and to compare it with the previous
      program. In addition, some preliminary results from 2007 to 2009 were presented.
      Lastly, we suggest several points that need to be considered to improve the
      program such as enhancement of participation rates, necessity of specialized
      committee and research for current screening program to be supported by evidence.

PMID- 22661876
TI  - Biomedical ethics policy in Korea: characteristics and historical development.
AB  - Ethical consideration is an inseparable part of policy-making in modern society.
      Biomedical ethics is an interdisciplinary study of ethical issues that result
      from advances in medical practices and research. Because these issues often arise
      at the bedside, society must provide solutions or judgments that are effective
      and applicable. Thus, the development and progress of biomedical ethics has been
      made possible via the cooperation of experts from diverse backgrounds. The
      biomedical ethics discourse should not be seen as a conflict between values but
      as a collective activity for problem-solving. To support this perspective on
      ethics discourse, a historical perspective on biomedical ethics in Korea was
      given emphasis on the participants and their perspectives. Major cases and the
      changes resulting therefrom were discussed with the agenda proposed. The Korean
      situation with respect to ethics development shows the interactions between
      groups participating in policy development and its collaborative nature.

PMID- 22661877
TI  - Discussions and implications of the recent enactment & revision of the healthcare
      law.
AB  - Recently, there have been many changes in the area of healthcare. There is no
      certainty how these changes will affect the healthcare system and public health.
      However, to at least have these changes positively implemented, it is clear that
      evaluation through continuous monitoring is necessary. The enforcement of the
      Medical Institution Accreditation and Medical Dispute Mediation Law as well as
      legal revisions regarding the public healthcare system are changes to improve the
      quality of healthcare, while at the same time, provide penalties for infractions
      of the new law such as medicine/medical device rebates; moreover, legal revisions
      regarding telemedicine are anticipated to impartially vitalize technical
      development as well as the pharmaceutical industry. For these changes to have a
      positive effect on the medical field and people's lives, an accurate
      comprehension of the system and understanding of the details is necessary to be
      able to respond sensitively to any changes in the future. Therefore, this paper
      examined the background information on the current discussion on the changes in
      the healthcare system, examined the detailed content of the system, and reviewed
      the areas that were in dispute as well as the main issues to contemplate the
      expected effects of the changes and future tasks that may be generated as a
      result. These considerations will act as foundation for an in depth understanding
      of recent trends in the healthcare system.

PMID- 22661878
TI  - Parenting a Child with a Disability: The Role of Social Support for African
      American Parents.
AB  - This paper examines: (1) the impact of having a child with a disability on
      parents' mental and physical health among urban-dwelling African Americans and
      (2) the extent to which positive and negative social interactions with family
      other than the spouse moderate the impact of child's disability on parental
      adaptation. Analyses are based on a probability sample of African Americans
      living in Milwaukee, Wisconsin. The analytic sample includes 48 parents of a
      child with a disability and 144 comparison group parents of non-disabled
      children. Results showed that having a child with a disability is associated with
      more somatic symptoms. However, the negative consequences of the child's
      disability on parents' mental health are reduced when parents receive greater
      positive support from family.

PMID- 22661879
TI  - Community and Individual Factors Associated with Cigarette Smoking Among Young
      Men Who Have Sex With Men.
AB  - Young men who have sex with men (YMSM) have higher rates of cigarette smoking
      than their heterosexual counterparts, yet few studies have examined factors
      associated with cigarette smoking among YMSM. The present study sought to
      understand how different types of gay community connection (i.e., gay community
      identification and involvement, gay bar/club attendance) were associated with
      smoking among YMSM recruited through venue-based sampling in Los Angeles,
      California (N = 526). Structural equation modeling was used to isolate direct and
      indirect effects of gay community connection on smoking through cognitive and
      psychological mediators (i.e., psychological distress, health values,
      internalized homophobia). Findings indicate YMSM cigarette smoking prevention and
      intervention must be tailored to address the direct and indirect influences of
      the gay community.

PMID- 22661880
TI  - Embedding Number-Combinations Practice Within Word-Problem Tutoring.
AB  - Two aspects of mathematics with which students with mathematics learning
      difficulty (MLD) often struggle are word problems and number-combination skills.
      This article describes a math program in which students receive instruction on
      using algebraic equations to represent the underlying problem structure for three
      word-problem types. Students also learn counting strategies for answering number
      combinations that they cannot retrieve from memory. Results from randomized
      control trials indicated that embedding the counting strategies for number
      combinations produces superior word-problem and number-combination outcomes for
      students with MLD beyond tutoring programs that focus exclusively on number
      combinations or word problems.

PMID- 22661881
TI  - Egg production forecasting: Determining efficient modeling approaches.
AB  - Several mathematical or statistical and artificial intelligence models were
      developed to compare egg production forecasts in commercial layers. Initial data
      for these models were collected from a comparative layer trial on commercial
      strains conducted at the Poultry Research Farms, Auburn University. Simulated
      data were produced to represent new scenarios by using means and SD of egg
      production of the 22 commercial strains. From the simulated data, random examples
      were generated for neural network training and testing for the weekly egg
      production prediction from wk 22 to 36. Three neural network architectures-back
      propagation-3, Ward-5, and the general regression neural network-were compared
      for their efficiency to forecast egg production, along with other traditional
      models. The general regression neural network gave the best-fitting line, which
      almost overlapped with the commercial egg production data, with an R(2) of 0.71.
      The general regression neural network-predicted curve was compared with original
      egg production data, the average curves of white-shelled and brown-shelled
      strains, linear regression predictions, and the Gompertz nonlinear model. The
      general regression neural network was superior in all these comparisons and may
      be the model of choice if the initial overprediction is managed efficiently. In
      general, neural network models are efficient, are easy to use, require fewer
      data, and are practical under farm management conditions to forecast egg
      production.

PMID- 22661882
TI  - The FDA Review Process for Cardiac Medical Devices in Children: A Review for the
      Clinician.
AB  - Pediatric medical devices play a vital role in the treatment of children with
      cardiovascular disease. Most cardiac medical devices used in children today are
      used off-label where the risk-benefit of devices has not been well characterized.
      Pediatric medical devices face a variety of challenges to FDA approval related in
      large part to the small target population, heterogeneity of the patient
      population and ethical considerations of device testing in children. While
      relatively few cardiac devices have received FDA approval in children, the number
      of devices navigating the approval process successfully is growing. Most
      pediatric device approvals are being granted through the humanitarian device
      exemption (HDE) pathway, which is designed for rare diseases making it suitable
      for devices treating congenital heart disease. This review summarizes the FDA
      review process for pediatric medical devices as it continues to evolve in
      response to the unique challenges of understanding device performance in the
      pediatric population.

PMID- 22661883
TI  - The Role of Family Affect in Juvenile Drug Court Offenders' Substance Use and HIV
      Risk.
AB  - Family-based interventions targeting parenting factors, such as parental
      monitoring and parent-child communication, have been successful in reducing
      adolescent offenders' substance use and delinquency. This pilot, exploratory
      study focuses on family and parenting factors that may be relevant in reducing
      juvenile offenders' substance use and sexual risk taking behavior, and in
      particular examines the role of family emotional involvement and responsiveness
      in young offenders' risk-taking behaviors. Participants included 53 juvenile drug
      court offenders and their parents. Results indicate that poor parent-child
      communication is associated with marijuana use and unprotected sexual activity
      for young offenders; however, family affective responsiveness is also a
      significant unique predictor of unprotected sexual activity for these youth.
      Findings suggest that interventions focused on improving parent-child
      communication may reduce both marijuana use and risky sexual behavior among court
      involved youth, but a specific intervention focused on improving parents and
      young offenders' ability to connect with and respond to one another emotionally
      may provide a novel means of reducing unprotected sexual risk behaviors.

PMID- 22661884
TI  - Robust and Effective Component-based Banknote Recognition for the Blind.
AB  - We develop a novel camera-based computer vision technology to automatically
      recognize banknotes for assisting visually impaired people. Our banknote
      recognition system is robust and effective with the following features: 1) high
      accuracy: high true recognition rate and low false recognition rate, 2)
      robustness: handles a variety of currency designs and bills in various
      conditions, 3) high efficiency: recognizes banknotes quickly, and 4) ease of use:
      helps blind users to aim the target for image capture. To make the system robust
      to a variety of conditions including occlusion, rotation, scaling, cluttered
      background, illumination change, viewpoint variation, and worn or wrinkled bills,
      we propose a component-based framework by using Speeded Up Robust Features
      (SURF). Furthermore, we employ the spatial relationship of matched SURF features
      to detect if there is a bill in the camera view. This process largely alleviates
      false recognition and can guide the user to correctly aim at the bill to be
      recognized. The robustness and generalizability of the proposed system is
      evaluated on a dataset including both positive images (with U.S. banknotes) and
      negative images (no U.S. banknotes) collected under a variety of conditions. The
      proposed algorithm, achieves 100% true recognition rate and 0% false recognition
      rate. Our banknote recognition system is also tested by blind users.

PMID- 22661885
TI  - Cross-Reactivity Between Sulfonamides and Loop or Thiazide Diuretics: Is it a
      Theoretical or Actual Risk?
AB  - This is a case report of furosemide use in a woman with acute renal transplant
      rejection and history of anaphylaxis to sulfonamide and a review of the
      literature.

PMID- 22661886
TI  - Treating acute cystitis with biodegradable micelle-encapsulated quercetin.
AB  - Intravesical application of an anti-inflammatory drug is an efficient strategy
      for acute cystitis therapy. Quercetin (QU) is a potent anti-inflammatory agent;
      however, its poor water solubility restricts its clinical application. In an
      attempt to improve water solubility of QU, biodegradable monomethoxy
      poly(ethylene glycol)-poly(E-caprolactone) (MPEG-PCL) micelles were used to
      encapsulate QU by self-assembly methods, creating QU/MPEG-PCL micelles. These
      QU/MPEG-PCL micelles with DL of 7% had a mean particle size of <34 nm, and could
      release QU for an extended period in vitro. The in vivo study indicated that
      intravesical application of MPEG-PCL micelles did not induce any toxicity to the
      bladder, and could efficiently deliver cargo to the bladder. Moreover, the
      therapeutic efficiency of intravesical administration of QU/MPEG-PCL micelles on
      acute cystitis was evaluated in vivo. Results indicated that QU/MPEG-PCL micelle
      treatment efficiently reduced the edema and inflammatory cell infiltration of the
      bladder in an Escherichia coli-induced acute cystitis model. These data suggested
      that MPEG-PCL micelle was a candidate intravesical drug carrier, and QU/MPEG-PCL
      micelles may have potential application in acute cystitis therapy.

PMID- 22661887
TI  - Preparation and evaluation of polymeric microparticulates for improving cellular
      uptake of gemcitabine.
AB  - BACKGROUND: Gemcitabine must be administered at high doses to elicit the required
      therapeutic response because of its very short plasma half-life due to rapid
      metabolism. These high doses can have severe adverse effects. METHODS: In this
      study, polymeric microparticulate systems of gemcitabine were prepared using
      chitosan as a mucoadhesive polymer and Eudragit L100-55 as an enteric copolymer.
      The physicochemical and biopharmaceutical properties of the resulting systems
      were then evaluated. RESULTS: There was no endothermic peak for gemcitabine in
      any of the polymeric gemcitabine microparticulate systems, suggesting that
      gemcitabine was bound to chitosan and Eudragit L100-55 and its crystallinity was
      changed into an amorphous form. The polymeric gemcitabine microparticulate system
      showed more than 80% release of gemcitabine in 30 minutes in simulated intestinal
      fluid. When mucin particles were incubated with gemcitabine polymeric
      microparticulates, the zeta potential of the mucin particles was increased to
      1.57 mV, indicating that the polymeric gemcitabine microparticulates were
      attached to the mucin particles. Furthermore, the F53 polymeric gemcitabine
      microparticulates having 150 mg of chitosan showed a 3.8-fold increased uptake of
      gemcitabine into Caco-2 cells over 72 hours compared with gemcitabine solution
      alone. CONCLUSION: Overall, these results suggest that polymeric gemcitabine
      microparticulate systems could be used as carriers to help oral absorption of
      gemcitabine.

PMID- 22661888
TI  - Detection of micrometastases in lung cancer with magnetic nanoparticles and
      quantum dots.
AB  - Detection of micrometastases plays an important role in early-stage and recurrent
      cancer diagnosis. In the study, a new method of screening micrometastases of lung
      cancer in peripheral blood by magnetic nanoparticles (MNPs) and quantum dots
      (QDs) was developed to achieve early diagnosis and recurrence prevention. MNPs
      were prepared by combining miniemulsion polymerization and Stober coating
      methods. QDs were prepared by using Cd(Ac)(2) . 2H(2)O and oxygen-free NaHTe with
      thioglycolic acid as the stabilizer. The carbodiimide-mediated condensation
      method was used to couple pan-cytokeratin (pan-ck) antibody (Ab) to the surface
      of the MNPs, and Lunx and SP-A Abs to the surface of the QDs. After four kinds of
      epithelial tumor cells were enriched by MNPs coupled with pan-ck Ab (MNP-pan-ck),
      lung cancer cells A549 and SPC-A-1 were successfully identified by QDs with
      double-labeled Abs. Finally, 32 patients with non-small cell lung cancer (NSCLC)
      were collected, out of 26 cases with the enriched circulating tumor cells (CTCs),
      21 cases were successfully identified by QDs. Therefore, a new method was
      established in which MNP-pan-ck collected CTCs and QDs with double-labeled Abs
      could be used simultaneously to identify CTCs from NSCLC patients.

PMID- 22661889
TI  - Formulation, antileukemia mechanism, pharmacokinetics, and biodistribution of a
      novel liposomal emodin.
AB  - Emodin is a multifunctional Chinese traditional medicine with poor water
      solubility. D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a
      pegylated vitamin E derivate. In this study, a novel liposomal-emodin-conjugating
      TPGS was formulated and compared with methoxypolyethyleneglycol 2000-derivatized
      distearoyl-phosphatidylethanolamine (mPEG2000-DSPE) liposomal emodin. TPGS
      improved the encapsulation efficiency and stability of emodin egg
      phosphatidylcholine/cholesterol liposomes. A high encapsulation efficiency of
      95.2% +/- 3.0%, particle size of 121.1 +/- 44.9 nm, spherical ultrastructure, and
      sustained in vitro release of TPGS liposomal emodin were observed; these were
      similar to mPEG2000-DSPE liposomes. Only the zeta potential of -13.1 +/- 2.7 mV
      was significantly different to that for mPEG2000-DSPE liposomes. Compared to
      mPEG2000-DSPE liposomes, TPGS liposomes improved the cytotoxicity of emodin on
      leukemia cells by regulating the protein levels of myeloid cell leukemia 1 (Mcl
      1), B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein, which was further
      enhanced by transferrin. TPGS liposomes prolonged the circulation time of emodin
      in the blood, with the area under the concentration-time curve (AUC) 1.7 times
      larger than for free emodin and 0.91 times larger than for mPEG2000-DSPE
      liposomes. In addition, TPGS liposomes showed higher AUC for emodin in the lung
      and kidney than for mPEG2000-DSPE liposomes, and both liposomes elevated the
      amount of emodin in the heart. Overall, TPGS is a pegylated agent that could
      potentially be used to compose a stable liposomal emodin with enhanced
      therapeutics.

PMID- 22661890
TI  - Ultrasmall superparamagnetic iron oxide (USPIO)-based liposomes as magnetic
      resonance imaging probes.
AB  - BACKGROUND: Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate
      magnetic and/or paramagnetic nanoparticles. They are applied as contrast agents
      for magnetic resonance imaging (MRI). MLs have an advantage over free magnetic
      nanocores, in that various functional groups can be attached to the surface of
      liposomes for ligand-specific targeting. We have synthesized PEG-coated
      sterically-stabilized magnetic liposomes (sMLs) containing ultrasmall
      superparamagnetic iron oxides (USPIOs) with the aim of generating stable
      liposomal carriers equipped with a high payload of USPIOs for enhanced MRI
      contrast. METHODS: Regarding iron oxide nanoparticles, we have applied two
      different commercially available surface-coated USPIOs; sMLs synthesized and
      loaded with USPIOs were compared in terms of magnetization and colloidal
      stability. The average diameter size, morphology, phospholipid membrane fluidity,
      and the iron content of the sMLs were determined by dynamic light scattering
      (DLS), transmission electron microscopy (TEM), fluorescence polarization, and
      absorption spectroscopy, respectively. A colorimetric assay using potassium
      thiocyanate (KSCN) was performed to evaluate the encapsulation efficiency (EE%)
      to express the amount of iron enclosed into a liposome. Subsequently, MRI
      measurements were carried out in vitro in agarose gel phantoms to evaluate the
      signal enhancement on T1- and T2-weighted sequences of sMLs. To monitor the
      biodistribution and the clearance of the particles over time in vivo, sMLs were
      injected in wild type mice. RESULTS: DLS revealed a mean particle diameter of
      sMLs in the range between 100 and 200 nm, as confirmed by TEM. An effective iron
      oxide loading was achieved just for one type of USPIO, with an EE% between 74%
      and 92%, depending on the initial Fe concentration (being higher for lower
      amounts of Fe). MRI measurements demonstrated the applicability of these
      nanostructures as MRI probes. CONCLUSION: Our results show that the development
      of sMLs is strictly dependent on the physicochemical characteristics of the
      nanocores. Once established, sMLs can be further modified to enable noninvasive
      targeted molecular imaging.

PMID- 22661892
TI  - Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor
      model.
AB  - BACKGROUND: Celastrol, a Chinese herbal medicine, has shown antitumor activity
      against various tumor cell lines. However, the effect of celastrol on
      retinoblastoma has not yet been analyzed. Additionally, the poor water solubility
      of celastrol restricts further therapeutic applications. The goal of this study
      was to evaluate the effect of celastrol nanoparticles (CNPs) on retinoblastoma
      and to investigate the potential mechanisms involved. METHODS: Celastrol-loaded
      poly(ethylene glycol)-block-poly(E-caprolactone) nanopolymeric micelles were
      developed to improve the hydrophilicity of celastrol. The 2-(2-methoxy-4-
      nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulf-ophenyl)-2H tetrazolium monosodium
      salt (WST-8) assay was used to determine the inhibitory effect of CNPs on SO-Rb
      50 cell proliferation in vitro. Immunofluorescence was used to evaluate the
      apoptotic effect of CNPs on nuclear morphology, and flow cytometry was used to
      quantify cellular apoptosis. The expression of Bcl-2, Bax, NF-kappaB p65, and
      phospo-NF-kappaB p65 proteins was assessed by Western blotting. A human
      retinoblastoma xenograft model was used to evaluate the inhibitory effects of
      CNPs on retinoblastoma in NOD-SCID mice. Hematoxylin and eosin staining was used
      to assess the apoptotic effects of CNPs on retinoblastoma. RESULTS: CNPs inhibit
      the proliferation of SO-Rb 50 cells in a dose- and time-dependent manner with an
      IC(50) of 17.733 MUg/mL (celastrol-loading content: 7.36%) after exposure to CNPs
      for 48 hours. CNPs induce apoptosis in SO-Rb 50 cells in a dose-dependent manner.
      The expression of Bcl-2, NF-kappaB p65, and phospo-NF-kappaB p65 proteins
      decreased after exposure to CNPs 54.4 MUg/mL for 48 hours. Additionally, the
      Bax/Bcl-2 ratio increased, whereas the expression of Bax itself was not
      significantly altered. CNPs inhibit the growth of retinoblastoma and induce
      apoptosis in retinoblastoma cells in mice. CONCLUSION: CNPs inhibit the growth of
      retinoblastoma in mouse xenograft model by inducing apoptosis in SO-Rb 50 cells,
      which may be related to the increased Bax/Bcl-2 ratio and the inhibition of NF
      kappaB. CNPs may represent a potential alternative treatment for retinoblastoma.

PMID- 22661893
TI  - Study of the intra-arterial distribution of Fe3O4 nanoparticles in a model of
      colorectal neoplasm induced in rat liver by MRI and spectrometry.
AB  - PURPOSE: To evaluate, in an experimental model, the reliability of MRI for
      determining whether a higher iron concentration was obtained in tumor tissue than
      in normal liver parenchyma after intra-arterial administration of Fe3O4
      lipophilic nanoparticles. MATERIALS AND METHODS: WAG/RijCrl rats were inoculated
      in the left hepatic lobe with 25,000 syngeneic CC-531 colon adenocarcinoma cells,
      after which they were randomized into two groups: control (CG) and infused (IG).
      After confirming tumor induction, the IG rats received intra-arterial suspensions
      of Fe3O4 nanoparticles (2.6 mg) in Lipiodol(r) (0.15 mL). To calculate the iron
      concentration, [Fe], in the tumor and liver tissues of both groups of rats,
      measurements of signal intensity from the tumors, healthy liver tissue, and
      paravertebral muscles were made on a 1.5T MRI system in gradient-echo DP* and T2*
      weighted sequences. In addition, samples were collected to quantify the [Fe] by
      inductively coupled plasma-mass spectrometry (ICP-MS), as well as for
      histological analysis. Statistical analysis was performed with non-parametric
      tests, and Bland-Altman plots were produced; P values <0.05 were considered
      significant. RESULTS: In the CG rats (n = 23), the mean [Fe] values estimated by
      MRI and ICP-MS were 13.2 MUmol.g-1 and 5.9 MUmol.g-1, respectively, in the
      tumors, and 19.0 MUmol .g-1 and 11.7 MUmol.g-1, respectively, in the hepatic
      tissue. In the IG rats (n = 19), the values obtained by MRI and ICP-MS were 148.9
      MUmol.g-1 and 9.4 MUmol . g-1, respectively, in the tumors, and 115.3 MUmol.g-1
      and 11.6 MUmol.g-1, respectively, in the healthy liver tissue. The IG results
      revealed a clear disagreement between MRI and ICP-MS. In the comparative analysis
      between the groups regarding the [Fe] values obtained by ICP-MS, significant
      differences were found for the tumor samples (P < 0.001), but not for the hepatic
      tissue (P = 0.92). Under microscopy, scattered intravascular deposits of
      nanoparticles were observed, especially in the tumors. CONCLUSION: ICP-MS
      demonstrated significant uptake of exogenous iron in tumor tissue. MRI was useful
      for quantifying the [Fe] in the different tissues in the CG animals, but not in
      the IG animals. Although the irregular distribution of nanoparticles caused an
      important bias in the measurements obtained by MRI, the relative increase in iron
      content inside the tumor was suggested.

PMID- 22661891
TI  - Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell
      targeted nanoformulated antiretroviral drugs to human brain endothelial cells.
AB  - Despite the successes of antiretroviral therapy (ART), HIV-associated
      neurocognitive disorders remain prevalent in infected people. This is due, in
      part, to incomplete ART penetration across the blood-brain barrier (BBB) and
      lymph nodes and to the establishment of viral sanctuaries within the central
      nervous system. In efforts to improve ART delivery, our laboratories developed a
      macrophage-carriage system for nanoformulated crystalline ART (nanoART)
      (atazanavir, ritonavir, indinavir, and efavirenz). We demonstrate that nanoART
      transfer from mononuclear phagocytes (MP) to human brain microvascular
      endothelial cells (HBMEC) can be realized through cell-to-cell contacts, which
      can facilitate drug passage across the BBB. Coculturing of donor MP containing
      nanoART with recipient HBMEC facilitates intercellular particle transfer. NanoART
      uptake was observed in up to 52% of HBMEC with limited cytotoxicity. Folate
      coating of nanoART increased MP to HBMEC particle transfer by up to 77%. To
      translate the cell assays into relevant animal models of disease, ritonavir and
      atazanavir nanoformulations were injected into HIV-1-infected NOD/scid
      gamma(c)(null) mice reconstituted with human peripheral blood lymphocytes.
      Atazanavir and ritonavir levels in brains of mice treated with folate-coated
      nanoART were three- to four-fold higher than in mice treated with noncoated
      particles. This was associated with decreased viral load in the spleen and brain,
      and diminished brain CD11b-associated glial activation. We postulate that
      monocyte-macrophage transfer of nanoART to brain endothelial cells could
      facilitate drug entry into the brain.

PMID- 22661894
TI  - Lack of a relationship between circulating gamma-glutamyltransferase levels and
      carotid intima media thickness in hypertensive and diabetic patients.
AB  - BACKGROUND: By increasing the intracellular prooxidant burden, gamma
      glutamyltransferase (GGT) may accelerate atherosclerotic vascular disease. That
      noxious influence may be reflected by circulating enzyme levels, a correlate of
      cardiovascular risk factors, and a predictor of incident events. To evaluate this
      hypothesis, we tested the association between circulating GGT and common carotid
      intima-media thickness (CIMT), a surrogate index of systemic atherosclerotic
      involvement, in a large and well-characterized group of patients at risk of
      cardiovascular disease (CVD). PATIENTS: This study analyzed 548 patients with
      hypertension and/or diabetes and a widely prevalent history of CVD. Subjects with
      known hepatic disease and abnormal GGT values were excluded. METHODS: CIMT (B
      mode ultrasonography) values were the mean of four far-wall measurements at both
      common carotids. Metabolic syndrome (MetS) was diagnosed according to National
      Cholesterol Education Program-Adult Treatment Panel III criteria. Due to inherent
      sex-related differences in GGT levels, the data were analyzed separately in males
      and females in samples dichotomized by the median. RESULTS: The age-adjusted CIMT
      values did not differ by GGT levels in males or females. In contrast, the carotid
      wall was consistently thicker in patients with a history of CVD and MetS
      independent of age and concurrent GGT values. In both sexes, GGT was associated
      with key components of the MetS such as triglycerides, fasting plasma glucose,
      and body mass index. CONCLUSION: The data collected in this mixed group of
      hypertensive and/or diabetic patients with widely prevalent history of CVD do not
      support the concept of a direct pathophysiological link between GGT levels within
      reference limits and atherosclerotic involvement.

PMID- 22661895
TI  - Percutaneous mechanical thrombectomy for treatment of acute femoropopliteal
      bypass occlusion.
AB  - Acute and subacute ischemia of the legs in acute and subacute femoropopliteal
      bypass occlusion is a dramatic situation that endangers the survival of the
      limbs, depending on the severity of the ischemia. Different therapy options like
      percutaneous mechanical thrombectomy procedures, which include rotational
      thrombectomy, have become available in recent years, in addition to local lysis
      and surgical thrombectomy. Surgical thrombectomy using the Fogarty catheter
      technique, in particular, shows an increased incidence of perioperative
      complications but only small technical success rates in randomized trials. On the
      other hand, local lysis is associated with increased costs due to resource
      consuming measures, such as intensive monitoring and repeat angiographies, in
      addition to bleeding complications. In the past, further development of the
      Straub Rotarex((r)) system as an endovascular therapy option has demonstrated
      good success leading to amputation-free survival in multiple studies. At the same
      time, a low rate of complications with use has been documented. Most examinations
      have been conducted in the thigh. To date, there are little investigational data
      on its use in acutely and subacutely occluded femoropopliteal bypasses. In this
      paper, the current study-based significance of the Rotarex system for this
      indication is analyzed based on the existing literature and the authors' own
      experiences with 22 patients.

PMID- 22661896
TI  - Smoking status and sex as indicators of differences in 2582 obese patients
      presenting for weight management.
AB  - BACKGROUND: Smoking remains the most common preventable cause of death. Very
      little tobacco exposure can increase cardiovascular disease risk. The
      relationship between smoking, sex, and weight remains unclear. METHODS: Between
      September 1992 and June 2007, 2582 consenting patients starting the Ottawa
      Hospital Weight Management program were grouped by sex and smoking status.
      "Former smokers" (771 females, 312 males) had quit for at least 1 year. "Smokers"
      (135 females, 54 males) smoked > 9 cigarettes daily. There were 979 females and
      331 males who never smoked. Using SAS 9.2 statistical software, the prevalence of
      coronary artery disease (CAD), type 2 diabetes (T2DM), major depressive disorder
      (MDD), and medication use among the groups was compared (Chi-square [chi(2)]).
      Anthropometric measurements, lipid, glucose and thyroid levels were compared
      using analysis of variance (ANOVA). Interactions were assessed using 2-way ANOVA
      analysis for continuous data, and logistic regression for discrete data. RESULTS:
      Smokers were more likely to have MDD (chi(2)), lower high-density lipoprotein
      levels and higher triglyceride levels than other groups. Former smokers had a
      greater prevalence of CAD, T2DM on pharmacotherapy, and impaired fasting glucose
      than other groups. They were also more likely to be taking lipid-lowering agents
      and antihypertensives (chi(2)). Never smokers had less MDD, CAD, and were less
      likely to be on antidepressants than the other groups. Males were more likely to
      have CAD and T2DM than females. Females were more likely to have MDD than males.
      Interactions between smoking status and sex were found for age, weight, fasting
      glucose and thyroid-stimulating hormone levels. CONCLUSION: Obese never smokers
      suffer from the fewest chronic diseases. Obese former smokers have a greater
      prevalence of CAD, T2DM on pharmacotherapy, and impaired fasting glucose than
      other groups. Thus, clinicians and researchers should avoid combining former
      smokers with never smokers as "nonsmokers" in research and treatment decisions.
      The results of this study call for a longitudinal study comparing these groups
      over the weight management program.

PMID- 22661897
TI  - Critical evaluation of the efficacy and tolerability of azilsartan.
AB  - Appropriate control of blood pressure (BP) in hypertensive patients still
      represents the major therapeutic goal in the treatment of hypertension. Despite
      the growing attention and wide range of antihypertensive agents available in the
      clinical scenario, the target of BP below the advised thresholds of 140/90 mmHg
      is, unfortunately, often unreached. For this reason, the search for new
      antihypertensive agents is still ongoing. Azilsartan medoxomil, a new angiotensin
      receptor blocker that has been recently introduced in the clinical arena,
      represents the eighth angiotensin receptor blocker currently available for BP
      control. The aim of this paper is to describe the efficacy and safety profile of
      this new compound, reviewing available data obtained from both pre-clinical and
      clinical studies.

PMID- 22661899
TI  - Cholesteryl ester transfer-protein modulator and inhibitors and their potential
      for the treatment of cardiovascular diseases.
AB  - Elevated low-density lipoprotein (LDL) cholesterol and lowered high-density
      lipoprotein (HDL) cholesterol are important risk factors for cardiovascular
      disease. Accordingly, raising HDL cholesterol induced by cholesteryl ester
      transfer protein (CETP) inhibition is an attractive approach for reducing the
      residual risk of cardiovascular events that persist in many patients receiving
      low-density LDL cholesterol-lowering therapy with statins. The development of
      torcetrapib, a CETP inhibitor, was terminated due to its adverse cardiovascular
      effects. These adverse effects did not influence the mechanism of CETP
      inhibition, but affected the molecule itself. Therefore a CETP modulator,
      dalcetrapib, and a CETP inhibitor, anacetrapib, are in Phase III of clinical
      trials to evaluate their effects on cardiovascular outcomes. In the dal-VESSEL
      (dalcetrapib Phase IIb endothelial function study) and the dal-PLAQUE (safety and
      efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive
      multimodality imaging) clinical studies, dalcetrapib reduced CETP activity by 50%
      and increased HDL cholesterol levels by 31% without changing LDL cholesterol
      levels. Moreover, dalcetrapib was associated with a reduction in carotid vessel
      wall inflammation at 6 months, as well as a reduced vessel-wall area at 24 months
      compared with the placebo. In the DEFINE (determining the efficacy and
      tolerability of CETP inhibition with anacetrapib) clinical study, anacetrapib
      increased HDL cholesterol levels by 138% and decreased LDL cholesterol levels by
      36%. In contrast with torcetrapib, anacetrapib had no adverse cardiovascular
      effects. The potential of dalcetrapib and anacetrapib in the treatment of
      cardiovascular diseases will be revealed by two large-scale clinical trials, the
      dal-OUTCOMES (efficacy and safety of dalcetrapib in patients with recent acute
      coronary syndrome) study and the REVEAL (randomized evaluation of the effects of
      anacetrapib through lipid modification, a large-scale, randomized placebo
      controlled trial of the clinical effects of anacetrapib among people with
      established vascular disease) study. The dal-OUTCOMES study is testing whether
      dalcetrapib can reduce cardiovascular events and the REVEAL study is testing
      whether anacetrapib can reduce cardiovascular events. These reports are expected
      to be released by 2013 and 2017, respectively.

PMID- 22661901
TI  - Morphoea profunda presenting with atrophic skin lesions in a 26 year old female:
      a case report.
AB  - Morphoea Profunda is a rare variant of Morphoea that presents clinically as a
      solitary fibrotic plaque. Morphoea Profunda presenting with atrophic lesions has
      rarely been reported in literature. We report the case of a 26 year old Nepalese
      lady who presented to us with multiple non-inflammatory atrophic lesions on her
      body without significant skin induration, pigmentation and texture change. The
      findings on histopathology confirmed a diagnosis of Morphoea Profunda. Hence,
      Morphoea Profunda should be considered in the differential diagnosis of anyone
      presenting with asymptomatic atrophy of the skin.

PMID- 22661898
TI  - Use of carvedilol in hypertension: an update.
AB  - beta-blockers are effective antihypertensive agents and, together with diuretics,
      have been the cornerstone of pioneering studies showing their benefits on
      cardiovascular morbidity and mortality as a consequence of blood pressure
      reduction in patients with hypertension. However, evidence from recent meta
      analyses have demonstrated no benefit afforded by atenolol compared with placebo
      in risk of mortality, myocardial infarction, or stroke, and a higher risk of
      mortality and stroke with atenolol/propranolol compared with other
      antihypertensive drug classes. Thus, the effect of these agents on cardiovascular
      morbidity and mortality in hypertensive patients, especially their use in
      uncomplicated hypertension, has remained largely controversial. However, it is
      recognized that the clinical studies used in these meta-analyses were mainly
      based on the older second-generation beta-blockers, such as atenolol and
      metoprolol. Actually, considerable heterogeneity in, eg, pharmacokinetic,
      pharmacological, and physicochemical properties exists across the different
      classes of beta-blockers, particularly between the second-generation and newer
      third-generation agents. Carvedilol is a vasodilating noncardioselective third
      generation beta-blocker, without the negative hemodynamic and metabolic effects
      of traditional beta-blockers, which can be used as a cardioprotective agent.
      Compared with conventional beta-blockers, carvedilol maintains cardiac output,
      has a reduced prolonged effect on heart rate, and reduces blood pressure by
      decreasing vascular resistance. Studies have also shown that carvedilol exhibits
      favorable effects on metabolic parameters, eg, glycemic control, insulin
      sensitivity, and lipid metabolism, suggesting that it could be considered in the
      treatment of patients with metabolic syndrome or diabetes. The present report
      provides an overview of the main clinical studies concerning carvedilol
      administered as either monotherapy or in combination with another
      antihypertensive or more frequently a diuretic agent, with particular focus on
      the additional benefits beyond blood pressure reduction.

PMID- 22661900
TI  - Evidence to support the use of vildagliptin monotherapy in the treatment of type
      2 diabetes mellitus.
AB  - The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, vildagliptin, as
      monotherapy have been widely confirmed in a large body of clinical studies of up
      to 2 years' duration in various populations with type 2 diabetes mellitus. This
      paper reviews the data supporting the use of vildagliptin in monotherapy.
      Consideration based on baseline glycated hemoglobin levels and age is given to
      patient segments where metformin is not appropriate. In addition, although
      prediabetes is not an indication, this manuscript briefly reviews some of the
      existing data showing that the mechanisms at work in diabetic populations are
      active in patients currently classified as prediabetic, with impaired glucose
      tolerance or impaired fasting glucose. Finally, the rationale for vildagliptin
      dosing frequency in monotherapy is discussed. In summary, this review aims to
      define where in community practice the use of vildagliptin as monotherapy is most
      desirable, focusing on segments of the population with type 2 diabetes mellitus
      that might receive the greatest benefit from vildagliptin in the management of
      their disease.

PMID- 22661902
TI  - Leiomyomatosis peritonealis disseminata associated with endometriosis and
      multiple uterus-like mass: report of two cases.
AB  - Leiomyomatosis peritonealis disseminate (LPD) is a rare benign disease of unknown
      etiology of women in reproductive age. A few reported cases of association with
      endometriosis have been described suggesting a possible origin from
      submesothelial multipotential cells. We present two cases of LPD associated with
      endometriosis expressing smooth muscle metaplasia, and some of the nodules with
      aspects of uterus-like mass. Laparoscopy, gross findings, and the pathological
      and immunohistochemical study of the surgical specimens were described. Our
      findings suggest an endometriotic origin for the LPD and indicate that the
      therapeutic approach might contemplate the surgical reduction of the nodules and
      endometriosis treatment.

PMID- 22661903
TI  - Paraganglioma of prostatic origin.
AB  - INTRODUCTION: Paragangliomas are usually benign tumors arising from chromaffin
      cells located outside the adrenal gland. Prostatic paraganglioma is an unusual
      entity in adult patients, with only 10 cases reported in the medical literature.
      CASE REPORT: A 34-year-old male with a history of chronic prostatitis consulted
      for perineal pain. On digital rectal examination the prostate was enlarged and
      firm, without nodules. The PSA level was 0.8 ng/mL and the catecholamines in the
      urine were elevated. On ultrasound a retrovesical 9 cm mass of undetermined
      origin measuring was present. A PET-CT scan showed a pelvic lesion measuring 9 cm
      with moderate increase in glucidic metabolism localized in the area of the
      prostate. A biopsy of the prostate revealed a neuroendocrine tumor, possibly a
      prostatic paraganglioma. A body scintigraphy with MIBG I-123 ruled out the
      presence of metastases or multifocal tumor. A radical prostatectomy with excision
      of the pelvic mass was performed under adrenergic blockade. One year after
      surgery the patient is asymptomatic and disease free. DISCUSSION/CONCLUSIONS:
      Prostatic paraganglioma is a rare, usually benign tumor, which should be
      considered in the differential diagnosis of prostate tumors in young males. Its
      diagnosis is based on the determination of catecholamine in blood and 24-hour
      urine and in imaging studies principally scintigraphy with MIBG I-123. Diagnostic
      confirmation is by histopathological study. The treatment consists of radical
      resection under adrenergic blockade and volume expansion. Given the limited
      number of cases reported, it is difficult to establish prognostic factors.
      Malignancy is defined by clinical criteria, and requires life long follow-up.

PMID- 22661904
TI  - Comparison of KRAS Mutation Assessment in Tumor DNA and Circulating Free DNA in
      Plasma and Serum Samples.
AB  - Testing for mutations in the KRAS oncogene for patients with metastatic
      colorectal cancer (mCRC) is generally performed using DNA from formalin-fixed
      paraffin-embedded tumor tissue; however, access to specimens can be limited and
      analysis challenging. This study assessed the identification of KRAS mutations in
      circulating free DNA (cfDNA) using a commercially available KRAS polymerase chain
      reaction (PCR) kit. Matched plasma, serum and tumor samples were available from
      71 patients with mCRC who had received prior therapy but whose disease progressed
      following therapy. Yields of cfDNA from plasma and serum samples were comparable.
      Analyses were successful in 70/71 plasma-extracted samples (specificity: 97%,
      sensitivity: 31%) and 67/71 serum- extracted samples (specificity: 100%,
      sensitivity: 25%). This study demonstrates that KRAS mutations can be detected in
      cfDNA using a commercially available KRAS PCR kit, confirming cfDNA as a
      potential alternative source of tumor DNA in a diagnostic setting if access to
      archival tumor specimens is limited.

PMID- 22661905
TI  - Emotional conflict and social context.
AB  - This paper aims to move the debate over the status of the conflict between
      emotion and judgement forward by refuting three implicit claims: that conflict
      between emotion and judgement is always to be avoided; that any conflict should
      always be resolved and, moreover, that it should be resolved immediately; that
      judgement should usually take priority in any resolution. Refutation of these
      three claims leads to recognition of the wide variety of different cases of
      conflict between emotion and judgement; examination of these cases is aided by
      consideration of the social context in which the conflicts occur.

PMID- 22661906
TI  - Dissemination of Cognitive Therapy for Panic Disorder in Primary Care.
AB  - This study investigated whether brief training in cognitive therapy for panic
      disorder (Clark et al., 1994) can improve the outcomes that primary care
      therapists obtain with their patients. Seven primary care therapists treated 36
      patients meeting DSM-IV (APA, 1994) criteria for panic disorder with or without
      agoraphobia in general practice surgeries. Outcomes for the cohort of patients
      whom the therapists treated with their usual methods (treatment-as-usual) before
      the training (N = 12) were compared with those obtained with similar patients
      treated by the same therapists after brief training and ongoing supervision in
      cognitive therapy (CT) for panic disorder (N = 24). Treatment-as-usual led to
      significant improvements in panic severity, general anxiety, and depression.
      However, only a small proportion (17% of the intent-to-treat sample) became panic
      free and there was no improvement in agoraphobic avoidance. Patients treated with
      CT achieved significantly better outcomes on all measures of panic attacks,
      including panic-free rate (54%, intent-to-treat), and showed significantly
      greater improvements in agoraphobic avoidance and patient-rated general anxiety.
      In conclusion, cognitive therapy for panic disorder can be successfully
      disseminated in primary care with a brief therapist training and supervision
      programme that leads to significant improvements in patient outcomes.

PMID- 22661907
TI  - The First Slow Step: Differential Effects of Object and Word-Form Familiarization
      on Retention of Fast-Mapped Words.
AB  - Recent research demonstrated that although twenty-four month-old infants do well
      on the initial pairing of a novel word and novel object in fast-mapping tasks,
      they are unable to retain the mapping after a five-minute delay. The current
      study examines the role of familiarity with the objects and words on infants'
      ability to bridge between the initial fast mapping of a name and object, and
      later retention in the service of slow mapping. Twenty-four-month-old infants
      were familiarized with either novel objects or novel names prior to the referent
      selection portion of a fast-mapping task. When familiarized with the novel
      objects, infants retained the novel mapping after a delay, but not when
      familiarized with the novel words. This suggests familiarity with the object
      versus the word form leads to differential encoding of the name-object link. We
      discuss the implications of this finding for subsequent slow mapping.

PMID- 22661908
TI  - Assessing Danger: What Judges Need To Know.
AB  - Every day, judges are faced with decisions regarding intimate partner violence
      (IPV) victims' requests for protection orders, custody arrangements, and
      visitation schedules. To make informed decisions, judges must understand victims'
      risk for future violence. This mixed method study explores the extent to which
      protection order petitions (n=169) communicate victims' current danger and future
      risk of violence. Methods included interviews coupled with an archival review of
      court petitions. Findings suggest judges are inadequately prepared to render
      decisions to improve victim safety in the absence of standardized risk
      assessments. The Danger Assessment provides an evidence-based solution to
      routinize intake interviews with victims petitioning the court.

PMID- 22661909
TI  - A Latent Growth Mixture Modeling Approach to PTSD Symptoms in Rape Victims.
AB  - The research literature has suggested that longitudinal changes in posttraumatic
      stress disorder (PTSD) could be adequately described in terms of one universal
      trajectory, with individual differences in baseline levels (intercept) and rate
      of change (slope) being negligible. However, not everyone who has experienced a
      trauma is diagnosed with PTSD, and symptom severity levels differ between
      individuals exposed to similar traumas. The current study employed the latent
      growth mixture modeling technique to test for multiple trajectories using data
      from a sample of Danish rape victims (N = 255). In addition, the analysis aimed
      to determine whether a number of explanatory variables could differentiate
      between the trajectories (age, acute stress disorder [ASD], and perceived social
      support). Results concluded the existence of two PTSD trajectories. ASD was found
      to be the only significant predictor of one trajectory characterized by high
      initial levels of PTSD symptomatology. The present findings confirmed the
      existence of multiple trajectories with regard to PTSD symptomatology in a way
      that may be useful to clinicians working with this population.

PMID- 22661910
TI  - Psychopathy in Adolescence Predicts Official Reports of Offending in Adulthood.
AB  - The present study examines the incremental predictive utility of psychopathy
      assessed at age 13 using the Childhood Psychopathy Scale (CPS) in predicting
      official records of arrests and convictions between the ages of 18 and 26. Data
      from 338 men from the middle sample of the Pittsburg Youth Study were used. A
      variety of control variables were included: demographics (race, family structure,
      SES, and neighborhood SES), parenting (physical punishment, inconsistent
      discipline, lax supervision, and low positive parenting), peer delinquency, and
      individual difference variables (impulsivity, Verbal IQ, Attention
      Deficit/Hyperactivity Disorder, and Conduct Disorder). CPS scores at age 13
      predicted the variety of arrests and convictions 5 to 13 years later, even after
      controlling for other well-established and well-measured risk factors. It is
      concluded that juvenile psychopathy is an important and useful risk factor for
      future antisocial behavior. Implications of these findings and reasons for
      resistance to the juvenile psychopathy construct are discussed.

PMID- 22661911
TI  - Hierarchical Order Parameters for Macromolecular Assembly Simulations I:
      Construction and Dynamical Properties of Order Parameters.
AB  - Macromolecular assemblies often display a hierarchical organization of
      macromolecules or their sub-assemblies. To model this, we have formulated a space
      warping method that enables capturing overall macromolecular structure and
      dynamics via a set of coarse-grained order parameters (OPs). This article is the
      first of two describing the construction and computational implementation of an
      additional class of OPs that has built into them the hierarchical architecture of
      macromolecular assemblies. To accomplish this, first, the system is divided into
      subsystems, each of which is described via a representative set of OPs. Then, a
      global set of variables is constructed from these subsystem-centered OPs to
      capture overall system organization. Dynamical properties of the resulting OPs
      are compared to those of our previous nonhierarchical ones, and implied
      conceptual and computational advantages are discussed for a 100ns, 2 million atom
      solvated Human Papillomavirus-like particle simulation. In the second article,
      the hierarchical OPs are shown to enable a multiscale analysis that starts with
      the N-atom Liouville equation and yields rigorous Langevin equations of
      stochastic OP dynamics. The latter is demonstrated via a force-field based
      simulation algorithm that probes key structural transition pathways,
      simultaneously accounting for all-atom details and overall structure.

PMID- 22661912
TI  - Comparison of Four Different Shields for Birdcage-Type Coils with Experiments and
      Numerical Calculations.
AB  - Four 12-rung linear birdcage-type coils were built to experimentally examine the
      effects of the end-ring/shield configuration on radiofrequency magnetic field
      (B(1)) homogeneity and SNR at 125 MHz. The coil configurations include (a) a
      cylindrical shield (conventional), (b) a shield with annular extensions to
      closely shield the end-rings (surrounding shield), (c) a shield with annular
      extensions connected to the rungs (solid connection), and (d) a shield with
      radially oriented conductors connected to the rungs (radial connection). These
      coils were also modeled closely with finite difference time domain (FDTD) methods
      to corroborate experimental findings. Images of a human head were acquired, and
      the signal-to-noise ratio (SNR) was measured on the central axial, sagittal, and
      coronal slices. B(1) field homogeneity in the unloaded coils was assessed on
      images of an oil phantom. Among the four configurations, the solid connection
      configuration has a lower SNR than the conventional configuration and the
      surrounding shield configuration but a higher SNR than the radial connection.
      Although there is no significant difference between the overall SNR of the
      conventional configuration and the surrounding shield configuration, the
      surrounding shield configuration has the potential to be tuned to higher
      frequencies than the conventional configuration. The conventional birdcage coil
      results in the most homogeneous B(1) field in the oil phantom. Numerical results
      are also compared with the experimental results.

PMID- 22661916
TI  - Comprehensive Reports on the Latest Advances in Gastroenterology and Hepatology
      From:: The 76th American College of Gastroenterology Annual Scientific Meeting
      and Postgraduate CourseOctober 28-November 2, 2011Washington, DCThe 62nd Annual
      Meeting of the American Association for the Study of Liver DiseasesNovember 4-8,
      2011San Francisco, California2011 Advances in Inflammatory Bowel Diseases/Crohn's
      & Colitis Foundations Clinical and Research ConferenceDecember 1-3,
      2011Hollywood, Florida.

PMID- 22661914
TI  - Collapse of telomere homeostasis in hematopoietic cells caused by heterozygous
      mutations in telomerase genes.
AB  - Telomerase activity is readily detectable in extracts from human hematopoietic
      stem and progenitor cells, but appears unable to maintain telomere length with
      proliferation in vitro and with age in vivo. We performed a detailed study of the
      telomere length by flow FISH analysis in leukocytes from 835 healthy individuals
      and 60 individuals with reduced telomerase activity. Healthy individuals showed a
      broad range in average telomere length in granulocytes and lymphocytes at any
      given age. The average telomere length declined with age at a rate that differed
      between age-specific breakpoints and between cell types. Gender differences
      between leukocyte telomere lengths were observed for all cell subsets studied;
      interestingly, this trend could already be detected at birth. Heterozygous
      carriers for mutations in either the telomerase reverse transcriptase (hTERT) or
      the telomerase RNA template (hTERC) gene displayed striking and comparable
      telomere length deficits. Further, non-carrier relatives of such heterozygous
      individuals had somewhat shorter leukocyte telomere lengths than expected; this
      difference was most profound for granulocytes. Failure to maintain telomere
      homeostasis as a result of partial telomerase deficiency is thought to trigger
      cell senescence or cell death, eventually causing tissue failure syndromes. Our
      data are consistent with these statements and suggest that the likelihood of
      similar processes occurring in normal individuals increases with age. Our work
      highlights the essential role of telomerase in the hematopoietic system and
      supports the notion that telomerase levels in hematopoietic cells, while limiting
      and unable to prevent overall telomere shortening, are nevertheless crucial to
      maintain telomere homeostasis with age.

PMID- 22661915
TI  - DNA demethylation and USF regulate the meiosis-specific expression of the mouse
      Miwi.
AB  - Miwi, a member of the Argonaute family, is required for initiating
      spermiogenesis; however, the mechanisms that regulate the expression of the Miwi
      gene remain unknown. By mutation analysis and transgenic models, we identified a
      303 bp proximal promoter region of the mouse Miwi gene, which controls specific
      expression from midpachytene spermatocytes to round spermatids during meiosis. We
      characterized the binding sites of transcription factors NF-Y (Nuclear Factor Y)
      and USF (Upstream Stimulatory Factor) within the core promoter and found that
      both factors specifically bind to and activate the Miwi promoter. Methylation
      profiling of three CpG islands within the proximal promoter reveals a markedly
      inverse correlation between the methylation status of the CpG islands and germ
      cell type-specific expression of Miwi. CpG methylation at the USF-binding site
      within the E2 box in the promoter inhibits the binding of USF. Transgenic Miwi
      EGFP and endogenous Miwi reveal a subcellular co-localization pattern in the germ
      cells of the Miwi-EGFP transgenic mouse. Furthermore, the DNA methylation profile
      of the Miwi promoter-driven transgene is consistent with that of the endogenous
      Miwi promoter, indicating that Miwi transgene is epigenetically modified through
      methylation in vivo to ensure its spatio-temporal expression. Our findings
      suggest that USF controls Miwi expression from midpachytene spermatocytes to
      round spermatids through methylation-mediated regulation. This work identifies an
      epigenetic regulation mechanism for the spatio-temporal expression of mouse Miwi
      during spermatogenesis.

PMID- 22661917
TI  - Sphingomyelin is associated with kidney disease in type 1 diabetes (The FinnDiane
      Study).
AB  - Diabetic kidney disease, diagnosed by urinary albumin excretion rate (AER), is a
      critical symptom of chronic vascular injury in diabetes, and is associated with
      dyslipidemia and increased mortality. We investigated serum lipids in 326
      subjects with type 1 diabetes: 56% of patients had normal AER, 17% had
      microalbuminuria (20 <= AER < 200 MUg/min or 30 <= AER < 300 mg/24 h) and 26% had
      overt kidney disease (macroalbuminuria AER >= 200 MUg/min or AER >= 300 mg/24 h).
      Lipoprotein subclass lipids and low-molecular-weight metabolites were quantified
      from native serum, and individual lipid species from the lipid extract of the
      native sample, using a proton NMR metabonomics platform. Sphingomyelin (odds
      ratio 2.53, P < 10(-7)), large VLDL cholesterol (odds ratio 2.36, P < 10(-10)),
      total triglycerides (odds ratio 1.88, P < 10(-6)), omega-9 and saturated fatty
      acids (odds ratio 1.82, P < 10(-5)), glucose disposal rate (odds ratio 0.44, P <
      10(-9)), large HDL cholesterol (odds ratio 0.39, P < 10(-9)) and glomerular
      filtration rate (odds ratio 0.19, P < 10(-10)) were associated with kidney
      disease. No associations were found for polyunsaturated fatty acids or
      phospholipids. Sphingomyelin was a significant regressor of urinary albumin (P <
      0.0001) in multivariate analysis with kidney function, glycemic control, body
      mass, blood pressure, triglycerides and HDL cholesterol. Kidney injury,
      sphingolipids and excess fatty acids have been linked in animal models-our
      exploratory approach provides independent support for this relationship in human
      patients with diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of
      this article (doi:10.1007/s11306-011-0343-y) contains supplementary material,
      which is available to authorized users.

PMID- 22661918
TI  - NMR protocol for determination of oxidation susceptibility of serum lipids and
      application of the protocol to a chocolate study.
AB  - A protocol for determination of oxidation susceptibility of serum lipids based on
      proton nuclear magnetic resonance ((1)H NMR) spectroscopy is presented and
      compared to the commonly used spectrophotometric method. Even though there are
      methodological differences between these two methods, the NMR-based oxidation
      susceptibility correlates well (r(2) = 0.73) with the lag time determined
      spectrophotometrically. In addition to the oxidizability of serum lipids, the NMR
      method provides also information about the lipid profile. The NMR oxidation assay
      was applied to the chocolate study including fasting serum samples (n = 45) from
      subjects who had consumed white (WC), dark (DC) or high-polyphenol chocolate
      (HPC) daily for 3 weeks. The oxidation susceptibility of serum lipids decreased
      in the HPC group, and there was a significant difference between the WC and HPC
      groups (P = 0.031). According to the random forest analysis, the consumption of
      the HPC chocolate induced changes to the amounts of HDL, phosphatidylcholine,
      sphingomyelin, and nervonic, docosahexaenoic and myristic acids. Furthermore,
      arachidonic, docosahexaenoic, docosapentaenoic and palmitic acids, gamma-glutamyl
      transferase, hemoglobin, HDL, phosphatidylcholine and choline containing
      phospholipids explained about 60% of the oxidation susceptibility values.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11306-011-0323-2) contains supplementary material, which is
      available to authorized users.

PMID- 22661919
TI  - Between Metabolite Relationships: an essential aspect of metabolic change.
AB  - Not only the levels of individual metabolites, but also the relations between the
      levels of different metabolites may indicate (experimentally induced) changes in
      a biological system. Component analysis methods in current 'standard' use for
      metabolomics, such as Principal Component Analysis (PCA), do not focus on changes
      in these relations. We therefore propose the concept of 'Between Metabolite
      Relationships' (BMRs): common changes in the covariance (or correlation) between
      all metabolites in an organism. Such structural changes may indicate metabolic
      change brought about by experimental manipulation but which are lost with
      standard data analysis methods. These BMRs can be analysed by the INdividual
      Differences SCALing (INDSCAL) method. First the BMR quantification is described
      and subsequently the INDSCAL method. Finally, two studies illustrate the power
      and the applicability of BMRs in metabolomics. The first study is about the
      induced plant response of cabbage to herbivory, of which BMRs are a considerable
      part. In the second study-a human nutritional intervention study of green tea
      extract-standard data analysis tools did not reveal any metabolic change,
      although the BMRs were considerably affected. The presented results show that
      BMRs can be easily implemented in a wide variety of metabolomic studies. They
      provide a new source of information to describe biological systems in a way that
      fits flawlessly into the next generation of systems biology questions, dealing
      with personalized responses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s11306-011-0316-1) contains supplementary
      material, which is available to authorized users.

PMID- 22661920
TI  - Cyclin-dependent kinases 4 and 6 control tumor progression and direct glucose
      oxidation in the pentose cycle.
AB  - Cyclin-dependent kinases CDK4 and CDK6 are essential for the control of the cell
      cycle through the G(1) phase. Aberrant expression of CDK4 and CDK6 is a hallmark
      of cancer, which would suggest that CDK4 and CDK6 are attractive targets for
      cancer therapy. Herein, we report that calcein AM (the calcein acetoxymethyl
      ester) is a potent specific inhibitor of CDK4 and CDK6 in HCT116 human colon
      adenocarcinoma cells, inhibiting retinoblastoma protein (pRb) phosphorylation and
      inducing cell cycle arrest in the G(1) phase. The metabolic effects of calcein AM
      on HCT116 cells were also evaluated and the flux between the oxidative and non
      oxidative branches of the pentose phosphate pathway was significantly altered. To
      elucidate whether these metabolic changes were due to the inhibition of CDK4 and
      CDK6, we also characterized the metabolic profile of a CDK4, CDK6 and CDK2 triple
      knockout of mouse embryonic fibroblasts. The results show that the metabolic
      profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the
      metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the
      inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non
      oxidative branches of the pentose phosphate pathway. Taken together, these
      results indicate that low doses of calcein can halt cell division and kill tumor
      cells. Thus, selective inhibition of CDK4 and CDK6 may be of greater
      pharmacological interest, since inhibitors of these kinases affect both cell
      cycle progression and the robust metabolic profile of tumors.

PMID- 22661921
TI  - GFP-tagged multimetal-tolerant bacteria and their detection in the rhizosphere of
      white mustard.
AB  - The introduction of rhizobacteria that tolerate heavy metals is a promising
      approach to support plants involved in phytoextraction and phytostabilisation. In
      this study, soil of a metal-mine wasteland was analyzed for the presence of metal
      tolerant bacterial isolates, and the tolerance patterns of the isolated strains
      for a number of heavy metals and antibiotics were compared. Several of the
      multimetal-tolerant strains were tagged with a broad host range reporter plasmid
      (i.e. pPROBE-NT) bearing a green fluorescent protein marker gene (gfp). Overall,
      the metal-tolerant isolates were predominately Gram-negative bacteria. Most of
      the strains showed a tolerance to five metals (Zn, Cu, Ni, Pb and Cd), but with
      differing tolerance patterns. From among the successfully tagged isolates, we
      used the transconjugant Pseudomonas putida G25 (pPROBE-NT) to inoculate white
      mustard seedlings. Despite a significant decrease in transconjugant abundance in
      the rhizosphere, the gfp-tagged cells survived on the root surfaces at a level
      previously reported for root colonisers.

PMID- 22661922
TI  - Transferable integrons of Gram-negative bacteria isolated from the gut of a wild
      boar in the buffer zone of a national park.
AB  - The aim of this study was to determine the presence of integron-bearing Gram
      negative bacteria in the gut of a wild boar (Sus scrofa L.) shot in the buffer
      zone of a national park. Five Gram-negative strains of Escherichia coli, Serratia
      odorifera, Hafnia alvei and Pseudomonas sp. were isolated. Four of these strains
      had class 2 integrase (intI2), and one harbored class 1 integrase (intI1). The
      integron-positive strains were multiresistant, i.e., resistant to at least three
      unrelated antibiotics. All of the integrons were transferred to E. coli J-53
      (Rif(R)) in a conjugation assay. The results showed that a number of
      multiresistant, integron-containing bacterial strains of different genera may
      inhabit a single individual of a wild animal, allowing the possibility of
      transfer of antimicrobial resistance genes.

PMID- 22661923
TI  - Analysis of early life influences on cognitive development in childhood using
      multilevel ordinal models.
AB  - Studies of cognitive development in children are often based on tests designed
      for specific ages. Examination of the changes of these scores over time may not
      be meaningful. This paper investigates the influence of early life factors on
      cognitive development using maths and reading test scores at ages 7, 11, and 16
      years in a British birth cohort born in 1958. The distributions of these test
      scores differ between ages, for example, 20% participants scored the top mark in
      the reading test at 7 and the distribution of reading score at 16 is heavily
      skewed. In this paper, we group participants into 5 ordered categories,
      approximately 20% in each category according to their test scores at each age.
      Multilevel models for a repeated ordinal outcome are applied to relate the
      ordinal scale of maths and reading ability to early life factors.

PMID- 22661924
TI  - Dynamic Roles of microRNAs in Neurogenesis.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the
      post-transcriptional level by mediating mRNA degradation or translational
      inhibition. MiRNAs are implicated in many biological functions, including
      neurogenesis. It has been shown that miRNAs regulate multiple steps of
      neurogenesis, from neural stem cell proliferation to neuronal differentiation and
      maturation. MiRNAs execute their functions in a dynamic and context-dependent
      manner by targeting diverse downstream target genes, from transcriptional factors
      to epigenetic regulators. Identifying context-specific target genes is
      instrumental for understanding the roles that miRNAs play in neurogenesis. This
      review summarizes our current state of knowledge on the dynamic roles that miRNAs
      play in neural stem cells and neurogenesis.

PMID- 22661925
TI  - Inflammasome-IL-1beta Signaling Mediates Ethanol Inhibition of Hippocampal
      Neurogenesis.
AB  - Regulation of hippocampal neurogenesis is poorly understood, but appears to
      contribute to mood and cognition. Ethanol and neuroinflammation are known to
      reduce neurogenesis. We have found that ethanol induces neuroinflammation
      supporting the hypothesis that ethanol induction of neuroinflammation contributes
      to ethanol inhibition of neurogenesis. To identify the key proinflammatory
      molecule that may be responsible for ethanol-impaired neurogenesis we used an ex
      vivo model of organotypic hippocampal-entorhinal cortex brain slice cultures.
      Here, we demonstrated a key role of proinflammatory cytokine IL-1beta signaling
      in mediating ethanol inhibition of neurogenesis. Ethanol inhibition of
      neurogenesis was reversed by neutralizing antibody to IL-1beta or blockade of the
      IL-1beta receptor with antagonist IL-1RIa. Ethanol-impaired neurogenesis is
      associated with strong induction of IL-1beta and inflammasome proteins NALP1 and
      NALP3 in both neurons and astrocytes. Blockade of IL-1beta synthesis with
      inflammasome inhibitors Parthenolide and Bay11708 significantly reversed ethanol
      inhibited neurogenesis. Furthermore, we also found that IL-1beta and inflammasome
      proteins NALP1 and NALP3 are increased in hippocampal neurons and astrocytes in
      postmortem alcoholic human brain. Together, these novel findings demonstrate that
      targeting inflammasome-IL-1beta signaling can normalize ethanol-impaired
      hippocampal neurogenesis, which may have therapeutic implications for treatment
      of cognitive impairment associated with hippocampal dysfunction in alcoholics.

PMID- 22661926
TI  - Who plays the strings in newborn analgesia at birth, vasopressin or oxytocin?

PMID- 22661927
TI  - RhoA is dispensable for axon guidance of sensory neurons in the mouse dorsal root
      ganglia.
AB  - RhoA, a member of the Rho family small GTPases, has been shown to play important
      roles in axon guidance. However, to date, the physiological function of RhoA in
      axon guidance events in vivo has not been determined genetically in animals. Here
      we show that RhoA mRNA is strongly expressed by sensory neurons in the developing
      mouse dorsal root ganglia (DRG). We have deleted RhoA in sensory neurons of the
      DRG using RhoA-floxed mice under the Wnt1-Cre driver in which Cre is strongly
      expressed in sensory neurons. Peripheral projections of sensory neurons appear
      normal and there are no detectable defects in the central projections of either
      cutaneous or proprioceptive sensory neurons in RhoA(f/f); Wnt1-Cre mice.
      Furthermore, a co-culture assay using DRG explants from RhoA(f/f); Wnt1-Cre
      embryos, and 293T cells expressing semaphorin3A (Sema3A) reveals that RhoA is not
      required for Sema3A-mediated axonal repulsion of sensory neurons. Expression of
      RhoC, a closely related family member, is increased in RhoA-deficient sensory
      neurons and may play a compensatory role in this context. Taken together, these
      genetic studies demonstrate that RhoA is dispensable for peripheral and central
      projections of sensory neurons in the DRG.

PMID- 22661929
TI  - Postnatal characterization of cells in the accessory olfactory bulb of wild type
      and reeler mice.
AB  - Olfaction is the most relevant chemosensory sense of the rodents. General odors
      are primarily detected by the main olfactory system while most pheromonal signals
      are received by the accessory olfactory system. The first relay in the brain
      occurs in the olfactory bulb, which is subdivided in the main and accessory
      olfactory bulb (MOB/AOB). Given that the cell generation time is different
      between AOB and MOB, and the cell characterization of AOB remains limited, the
      goal of this work was first, the definition of the layering of AOB/MOB and
      second, the determination of cellular phenotypes in the AOB in a time window
      corresponding to the early postnatal development. Moreover, since reelin (Reln)
      deficiency has been related to olfactory learning deficits, we analyzed reeler
      mice. First, we compared the layering between AOB and MOB at early embryonic
      stages. Then, cell phenotypes were established using specific neuronal and glial
      markers as well as the Reln adaptor protein Dab1 to analyse differences in both
      genetic backgrounds. There was no apparent difference in the cell phenotypes
      among AOB and MOB or between wild type (wt) and reeler animals. However, a
      disruption in the granular cell layer of reeler with respect to wt mice was
      observed. In conclusion, the AOB in Reln-deficient mice showed similar neuronal
      and glial cell types being only affected the organization of granular neurons.

PMID- 22661930
TI  - Adaptive function and brain evolution.

PMID- 22661928
TI  - Modulation of iron metabolism in aging and in Alzheimer's disease: relevance of
      the choroid plexus.
AB  - Iron is essential for mammalian cellular homeostasis. However, in excess, it
      promotes free radical formation and is associated with aging-related progressive
      deterioration and with neurodegenerative disorders such as Alzheimer's disease
      (AD). There are no mechanisms to excrete iron, which makes iron homeostasis a
      very tightly regulated process at the level of the intestinal absorption. Iron is
      believed to reach the brain through receptor-mediated endocytosis of iron-bound
      transferrin by the brain barriers, the blood-cerebrospinal fluid (CSF) barrier,
      formed by the choroid plexus (CP) epithelial cells and the blood-brain barrier
      (BBB) formed by the endothelial cells of the brain capillaries. Importantly, the
      CP epithelial cells are responsible for producing most of the CSF, the fluid that
      fills the brain ventricles and the subarachnoid space. Recently, the finding that
      the CP epithelial cells display all the machinery to locally control iron
      delivery into the CSF may suggest that the general and progressive senescence of
      the CP may be at the basis of the impairment of regional iron metabolism, iron
      mediated toxicity, and the increase in inflammation and oxidative stress that
      occurs with aging and, particularly, in AD.

PMID- 22661931
TI  - Centrifugal telencephalic afferent connections to the main and accessory
      olfactory bulbs.
AB  - Parallel to the olfactory system, most mammals possess an accessory olfactory or
      vomeronasal system. The olfactory and vomeronasal epithelia project to the main
      and accessory olfactory bulbs, which in turn project to adjacent areas of the
      telencephalon, respectively. New data indicate that projections arising from the
      main and accessory olfactory bulbs partially converge in the rostral
      telencephalon and are non-overlapping at caudal telencephalic levels. Therefore,
      the basal telencephalon should be reclassified in olfactory, vomeronasal, and
      mixed areas. On the other hand, it has been demonstrated that virtually all
      olfactory- and vomeronasal-recipient structures send reciprocal projections to
      the main and accessory olfactory bulbs, respectively. Further, non-chemosensory
      recipient structures also projects centrifugally to the olfactory bulbs. These
      feed-back projections appear to be essential modulating processing of
      chemosensory information. The present work aims at characterizing centrifugal
      projections to the main and accessory olfactory bulbs arising from olfactory,
      vomeronasal, mixed, and non-chemosensory recipient telencephalic areas. This
      issue has been addressed by using tracer injections in the rat and mouse brain.
      Tracer injections were delivered into the main and accessory olfactory bulbs as
      well as in olfactory, vomeronasal, mixed, and non-chemosensory recipient
      telencephalic structures. The results confirm that olfactory- and vomeronasal
      recipient structures project to the main and accessory olfactory bulbs,
      respectively. Interestingly, olfactory (e.g., piriform cortex), vomeronasal
      (e.g., posteromedial cortical amygdala), mixed (e.g., the anterior medial
      amygdaloid nucleus), and non-chemosensory-recipient (e.g., the nucleus of the
      diagonal band) structures project to the main and to the accessory olfactory
      bulbs thus providing the possibility of simultaneous modulation and interaction
      of both systems at different stages of chemosensory processing.

PMID- 22661932
TI  - Is the effect of tinnitus on auditory steady-state response amplitude mediated by
      attention?
AB  - OBJECTIVES: Auditory steady-state response (ASSR) amplitude enhancement effects
      have been reported in tinnitus patients. As ASSR amplitude is also enhanced by
      attention, the effect of tinnitus on ASSR amplitude could be interpreted as an
      effect of attention mediated by tinnitus. As N1 attention effects are
      significantly larger than those on the ASSR, if the effect of tinnitus on ASSR
      amplitude were due to attention, there should be similar amplitude enhancement
      effects in tinnitus for the N1 component of the auditory-evoked response.
      METHODS: MEG recordings which were previously examined for the ASSR (Diesch et
      al., 2010a) were analyzed with respect to the N1m component. Like the ASSR
      previously, the N1m was analyzed in the source domain (source space projection).
      Stimuli were amplitude-modulated (AM) tones with one of three carrier frequencies
      matching the tinnitus frequency or a surrogate frequency 11/2 octave above the
      audiometric edge frequency in controls, the audiometric edge frequency, and a
      frequency below the audiometric edge. Single AM-tones were presented in a single
      condition and superpositions of three AM-tones differing in carrier and
      modulation frequency in a composite condition. RESULTS: In the earlier ASSR study
      (Diesch et al., 2010a), the ASSR amplitude in tinnitus patients, but not in
      controls, was significantly larger in the (surrogate) tinnitus condition than in
      the edge condition. Patients showed less evidence than controls of reciprocal
      inhibition of component ASSR responses in the composite condition. In the present
      study, N1m amplitudes elicited by stimuli located at the audiometric edge and at
      the (surrogate) tinnitus frequency were smaller than N1m amplitudes elicited by
      sub-edge tones both in patients and controls. The relationship of the N1m
      response in the composite condition to the N1m response in the single condition
      indicated that reciprocal inhibition among component N1m responses was reduced in
      patients compared against controls. CONCLUSIONS: In the present study, no
      evidence was found for an N1-amplitude enhancement effect in tinnitus. Compared
      to controls, reciprocal inhibition is reduced in tinnitus patients. Thus, as
      there is no effect on N1m that could potentially be attributed to attention, it
      seems unlikely that the enhancement effect of tinnitus on ASSR amplitude could be
      accounted for in terms of attention induced by tinnitus.

PMID- 22661933
TI  - Upside down crossed cerebellar diaschisis: proposing chronic stimulation of the
      dentatothalamocortical pathway for post-stroke motor recovery.
AB  - BACKGROUND: Stroke remains the leading cause for long-term motor impairment in
      the industrialized world. New techniques are needed to improve outcomes.
      OBJECTIVE: To propose chronic electrical stimulation of the
      dentatothalamocortical pathway as a method for enhancing cortical excitability
      and improving motor recovery following stroke. METHOD: In previous studies, motor
      evoked potentials were derived from intracortical microstimulation and used to
      index cortical excitability in rats undergoing continuous, asynchronous deep
      cerebellar stimulation. In a separate set of experiments, the effect of chronic
      deep cerebellar stimulation on motor recovery was tested in rats following large
      ischemic strokes. RESULTS: Deep cerebellar stimulation modulated cortical
      excitability in a frequency-dependent fashion. Beta band stimulation yielded
      sustained increment in excitability and was associated with enhanced motor
      recovery compared to sham stimulation. CONCLUSION: Chronic deep cerebellar
      stimulation enhances recovery of motor function following large ischemic strokes
      in the rat, an effect that may be associated with increased cortical
      excitability. Given that deep brain stimulation is already a well established
      method, this new approach to motor recovery may be a viable option for human
      translation in stroke rehabilitation.

PMID- 22661934
TI  - Evidence for broad versus segregated projections from cholinergic and
      noradrenergic nuclei to functionally and anatomically discrete subregions of
      prefrontal cortex.
AB  - The prefrontal cortex (PFC) is implicated in a variety of cognitive and executive
      operations. However, this region is not a single functional unit; rather, it is
      composed of several functionally and anatomically distinct networks, including
      anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), and
      orbitofrontal cortex (OFC). These prefrontal subregions serve dissociable
      behavioral functions, and are unique in their afferent and efferent connections.
      Each of these subregions is innervated by ascending cholinergic and noradrenergic
      systems, each of which likewise has a distinct role in cognitive function; yet
      the distribution and projection patterns of cells in the source nuclei for these
      pathways have not been examined in great detail. In this study, fluorescent
      retrograde tracers were injected into ACC, mPFC, and OFC, and labeled cells were
      identified in the cholinergic nucleus basalis of Meynert (NBM) and noradrenergic
      nucleus locus coeruleus (LC). Injections into all three cortical regions
      consistently labeled cells primarily ipsilateral to the injection site with a
      minimal contralateral component. In NBM, retrogradely labeled neurons were
      scattered throughout the rostral half of the nucleus, whereas those in LC tended
      to cluster in the core of the nucleus, and were rarely localized within the
      rostral or caudal poles. In NBM, more than half of all retrogradely labeled cells
      possessed axon collaterals projecting two or more PFC subregions. In LC, however,
      only 4.3% of retrogradely labeled neurons possessed collaterals targeting any two
      prefrontal subregions simultaneously, and no cells were identified that projected
      to all three regions. Of all labeled LC neurons, 49.3% projected only to mPFC,
      28.5% projected only to OFC, and 18.0% projected only to ACC. These findings
      suggest that subsets of LC neurons may be capable of modulating neuronal activity
      in individual prefrontal subregions independently, whereas assemblies of NBM
      cells may exert a more unified influence on the three areas, simultaneously. This
      work emphasizes unique aspects of the cholinergic and noradrenergic projections
      to functionally and anatomically distinct subregions of PFC and provides insights
      regarding global versus segregated regulation of prefrontal operations by these
      neuromodulatory pathways.

PMID- 22661935
TI  - Neglect impairs explicit processing of the mental number line.
AB  - Converging evidence suggests that visuospatial attention plays a pivotal role in
      numerical processing, especially when the task involves the manipulation of
      numerical magnitudes. Visuospatial neglect impairs contralesional attentional
      orienting not only in perceptual but also in numerical space. Indeed, patients
      with left neglect show a bias toward larger numbers when mentally bisecting a
      numerical interval, as if they were neglecting its leftmost part. In contrast,
      their performance in parity judgments is unbiased, suggesting a dissociation
      between explicit and implicit processing of numerical magnitude. Here we further
      investigate the consequences of these visuospatial attention impairments on
      numerical processing and their interaction with task demands. Patients with right
      hemisphere damage, with and without left neglect, were administered both a number
      comparison and a parity judgment task that had identical stimuli and response
      requirements. Neglect patients' performance was normal in the parity task, when
      processing of numerical magnitude was implicit, whereas they showed
      characteristic biases in the number comparison task, when access to numerical
      magnitude was explicit. Compared to patients without neglect, they showed an
      asymmetric distance effect, with slowing of the number immediately smaller than
      (i.e., to the left of) the reference and a stronger SNARC effect, particularly
      for large numbers. The latter might index an exaggerated effect of number-space
      compatibility after ipsilesional (i.e., rightward) orienting in number space.
      Thus, the effect of neglect on the explicit processing of numerical magnitude can
      be understood in terms of both a failure to orient to smaller (i.e.,
      contralesional) magnitudes and a difficulty to disengage from larger (i.e.,
      ipsilesional) magnitudes on the number line, which resembles the disrupted
      pattern of attention orienting in visual space.

PMID- 22661936
TI  - Differential synchronization in default and task-specific networks of the human
      brain.
AB  - On a regional scale the brain is organized into dynamic functional networks. The
      activity within one of these, the default network, can be dissociated from that
      in other task-specific networks. All brain networks are connected structurally
      but evidently are only transiently connected functionally. One hypothesis as to
      how such transient functional coupling occurs is that network formation and
      dissolution is mediated by increases and decreases in oscillatory synchronization
      between constituent brain regions. If so, then we should be able to find
      transient differences in intra-network synchronization between the default
      network and a task-specific network. In order to investigate this hypothesis we
      conducted two experiments in which subjects engaged in a Sustained Attention to
      Response Task while having brain activity recorded via high-density
      electroencephalography (EEG). We found that during periods when attention was
      focused internally (mind wandering) there was significantly more neural phase
      synchronization between brain regions associated with the default network,
      whereas during periods when subjects were focused on performing the visual task
      there was significantly more neural phase synchrony within a task-specific brain
      network that shared some of the same brain regions. These differences in network
      synchrony occurred in each of theta, alpha, and gamma frequency bands. A similar
      pattern of differential oscillatory power changes, indicating modulation of local
      synchronization by attention state, was also found. These results provide further
      evidence that the human brain is intrinsically organized into default and task
      specific brain networks, and confirm that oscillatory synchronization is a
      potential mechanism for functional coupling within these networks.

PMID- 22661937
TI  - Rapid social perception is flexible: approach and avoidance motivational states
      shape P100 responses to other-race faces.
AB  - Research on person categorization suggests that people automatically and
      inflexibly categorize others according to group memberships, such as race.
      Consistent with this view, research using electroencephalography (EEG) has found
      that White participants tend to show an early difference in processing Black
      versus White faces. Yet, new research has shown that these ostensibly automatic
      biases may not be as inevitable as once thought and that motivational influences
      may be able to eliminate these biases. It is unclear, however, whether
      motivational influences shape the initial biases or whether these biases can only
      be modulated by later, controlled processes. Using EEG to examine the time course
      of biased processing, we manipulated approach and avoidance motivational states
      by having participants pull or push a joystick, respectively, while viewing White
      or Black faces. Consistent with previous work on own-race bias, we observed a
      greater P100 response to White than Black faces; however, this racial bias was
      attenuated in the approach condition. These data suggest that rapid social
      perception may be flexible and can be modulated by motivational states.

PMID- 22661939
TI  - Learned Non-Rigid Object Motion is a View-Invariant Cue to Recognizing Novel
      Objects.
AB  - There is evidence that observers use learned object motion to recognize objects.
      For instance, studies have shown that reversing the learned direction in which a
      rigid object rotated in depth impaired recognition accuracy. This motion reversal
      can be achieved by playing animation sequences of moving objects in reverse frame
      order. In the current study, we used this sequence-reversal manipulation to
      investigate whether observers encode the motion of dynamic objects in visual
      memory, and whether such dynamic representations are encoded in a way that is
      dependent on the viewing conditions. Participants first learned dynamic novel
      objects, presented as animation sequences. Following learning, they were then
      tested on their ability to recognize these learned objects when their animation
      sequence was shown in the same sequence order as during learning or in the
      reverse sequence order. In Experiment 1, we found that non-rigid motion
      contributed to recognition performance; that is, sequence-reversal decreased
      sensitivity across different tasks. In subsequent experiments, we tested the
      recognition of non-rigidly deforming (Experiment 2) and rigidly rotating
      (Experiment 3) objects across novel viewpoints. Recognition performance was
      affected by viewpoint changes for both experiments. Learned non-rigid motion
      continued to contribute to recognition performance and this benefit was the same
      across all viewpoint changes. By comparison, learned rigid motion did not
      contribute to recognition performance. These results suggest that non-rigid
      motion provides a source of information for recognizing dynamic objects, which is
      not affected by changes to viewpoint.

PMID- 22661938
TI  - The hippocampus supports multiple cognitive processes through relational binding
      and comparison.
AB  - It has been well established that the hippocampus plays a pivotal role in
      explicit long-term recognition memory. However, findings from amnesia, lesion and
      recording studies with non-human animals, eye-movement recording studies, and
      functional neuroimaging have recently converged upon a similar message: the
      functional reach of the hippocampus extends far beyond explicit recognition
      memory. Damage to the hippocampus affects performance on a number of cognitive
      tasks including recognition memory after short and long delays and visual
      discrimination. Additionally, with the advent of neuroimaging techniques that
      have fine spatial and temporal resolution, findings have emerged that show the
      elicitation of hippocampal responses within the first few 100 ms of stimulus/task
      onset. These responses occur for novel and previously viewed information during a
      time when perceptual processing is traditionally thought to occur, and long
      before overt recognition responses are made. We propose that the hippocampus is
      obligatorily involved in the binding of disparate elements across both space and
      time, and in the comparison of such relational memory representations.
      Furthermore, the hippocampus supports relational binding and comparison with or
      without conscious awareness for the relational representations that are formed,
      retrieved and/or compared. It is by virtue of these basic binding and comparison
      functions that the reach of the hippocampus extends beyond long-term recognition
      memory and underlies task performance in multiple cognitive domains.

PMID- 22661941
TI  - Aggregating post-publication peer reviews and ratings.
AB  - Allocating funding for research often entails the review of the publications
      authored by a scientist or a group of scientists. For practical reasons, in many
      cases this review cannot be performed by a sufficient number of specialists in
      the core domain of the reviewed publications. In the meanwhile, each scientist
      reads thoroughly, on average, about 88 scientific articles per year, and the
      evaluative information that scientists can provide about these articles is
      currently lost. I suggest that aggregating in an online database reviews or
      ratings on the publications that scientists read anyhow can provide important
      information that can revolutionize the evaluation processes that support funding
      decisions. I also suggest that such aggregation of reviews can be encouraged by a
      system that would provide a publicly available review portfolio for each
      scientist, without prejudicing the anonymity of reviews. I provide some
      quantitative estimates on the number and distribution of reviews and ratings that
      can be obtained.

PMID- 22661940
TI  - A single theoretical framework for circular features processing in humans:
      orientation and direction of motion compared.
AB  - Common computational principles underlie processing of various visual features in
      the cortex. They are considered to create similar patterns of contextual
      modulations in behavioral studies for different features as orientation and
      direction of motion. Here, I studied the possibility that a single theoretical
      framework, implemented in different visual areas, of circular feature coding and
      processing could explain these similarities in observations. Stimuli were created
      that allowed direct comparison of the contextual effects on orientation and
      motion direction with two different psychophysical probes: changes in weak and
      strong signal perception. One unique simplified theoretical model of circular
      feature coding including only inhibitory interactions, and decoding through
      standard vector average, successfully predicted the similarities in the two
      domains, while different feature population characteristics explained well the
      differences in modulation on both experimental probes. These results demonstrate
      how a single computational principle underlies processing of various features
      across the cortices.

PMID- 22661942
TI  - Detecting multineuronal temporal patterns in parallel spike trains.
AB  - We present a non-parametric and computationally efficient method that detects
      spatiotemporal firing patterns and pattern sequences in parallel spike trains and
      tests whether the observed numbers of repeating patterns and sequences on a given
      timescale are significantly different from those expected by chance. The method
      is generally applicable and uncovers coordinated activity with arbitrary
      precision by comparing it to appropriate surrogate data. The analysis of coherent
      patterns of spatially and temporally distributed spiking activity on various
      timescales enables the immediate tracking of diverse qualities of coordinated
      firing related to neuronal state changes and information processing. We apply the
      method to simulated data and multineuronal recordings from rat visual cortex and
      show that it reliably discriminates between data sets with random pattern
      occurrences and with additional exactly repeating spatiotemporal patterns and
      pattern sequences. Multineuronal cortical spiking activity appears to be
      precisely coordinated and exhibits a sequential organization beyond the cell
      assembly concept.

PMID- 22661943
TI  - Food addiction and obesity: do macronutrients matter?

PMID- 22661944
TI  - Route repetition and route retracing: effects of cognitive aging.
AB  - Retracing a recently traveled route is a frequent navigation task when learning
      novel routes or exploring unfamiliar environments. In the present study we
      utilized virtual environments technology to investigate age-related differences
      in repeating and retracing a learned route. In the training phase of the
      experiment participants were guided along a route consisting of multiple
      intersections each featuring one unique landmark. In the subsequent test phase,
      they were guided along short sections of the route and asked to indicate overall
      travel direction (repetition or retracing), the direction required to continue
      along the route, and the next landmark they would encounter. Results demonstrate
      age-related deficits in all three tasks. More specifically, in contrast to
      younger participants, the older participants had greater problems during route
      retracing than during route repetition. While route repetition can be solved with
      egocentric response or route strategies, successfully retracing a route requires
      allocentric processing. The age-related deficits in route retracing are discussed
      in the context of impaired allocentric processing and shift from allocentric to
      egocentric navigation strategies as a consequence of age-related hippocampal
      degeneration.

PMID- 22661945
TI  - Less efficient pattern separation may contribute to age-related spatial memory
      deficits.
AB  - Spatial memory deficits have been well-documented in older adults and may serve
      as an early indicator of mild cognitive impairment (MCI) or Alzheimer's disease
      (AD) in some individuals. Pattern separation is a critical mechanism for reducing
      potential interference among similar memory representations to enhance memory
      accuracy. A small but growing literature indicates that spatial pattern
      separation may become less efficient as a result of normal aging, possibly due to
      age-related changes in subregions of the hippocampus. This decreased efficiency
      in spatial pattern separation may be a critical processing deficit that could be
      a contributing factor to spatial memory deficits and episodic memory impairment
      associated with aging. The present paper will review recently published studies
      in humans, non-human primates, and rodents that have examined age-related changes
      in spatial pattern separation. The potential basic science, translational, and
      clinical implications from these studies are discussed to illustrate the need for
      future research to further examine the relationship between spatial pattern
      separation and brain changes associated with aging and neurodegenerative disease.

PMID- 22661947
TI  - A Distinct Profile of Tryptophan Metabolism along the Kynurenine Pathway
      Downstream of Toll-Like Receptor Activation in Irritable Bowel Syndrome.
AB  - Irritable bowel syndrome (IBS), a disorder of the brain-gut axis, is
      characterised by the absence of reliable biological markers. Tryptophan is an
      essential amino acid that serves as a precursor to serotonin but which can
      alternatively be metabolised along the kynurenine pathway leading to the
      production of other neuroactive agents. We previously reported an increased
      degradation of tryptophan along this immunoresponsive pathway in IBS. Recently,
      altered cytokine production following activation of specific members of the toll
      like receptor (TLR) family (TLR1-9) has also been demonstrated in IBS. However,
      the relationship between TLR activation and kynurenine pathway activity in IBS is
      unknown. In this study, we investigated whether activation of specific TLRs
      elicits exaggerated kynurenine production in IBS patients compared to controls.
      Whole blood from IBS patients and healthy controls was cultured with a panel of
      nine different TLR agonists for 24 h. Cell culture supernatants were then
      analyzed for both tryptophan and kynurenine concentrations, as were plasma
      samples from both cohorts. IBS subjects had an elevated plasma
      kynurenine:tryptophan ratio compared to healthy controls. Furthermore, we
      demonstrated a differential downstream profile of kynurenine production
      subsequent to TLR activation in IBS patients compared to healthy controls. This
      profile included alterations at TLR1/2, TLR2, TLR3, TLR5, TLR7, and TLR8. Our
      data expands on our previous understanding of altered tryptophan metabolism in
      IBS and suggests that measurement of tryptophan metabolites downstream of TLR
      activation may ultimately find utility as components of a biomarker panel to aid
      gastroenterologists in the diagnosis of IBS. Furthermore, these studies implicate
      the modulation of TLRs as means through which aberrant tryptophan metabolism
      along the kynurenine pathway can be controlled, a novel potential therapeutic
      strategy in this and other disorders.

PMID- 22661948
TI  - Physiologically Based Pharmacokinetic Modeling of Tamoxifen and its Metabolites
      in Women of Different CYP2D6 Phenotypes Provides New Insight into the Tamoxifen
      Mass Balance.
AB  - Tamoxifen is a first-line endocrine agent in the mechanism-based treatment of
      estrogen receptor positive (ER(+)) mammary carcinoma and applied to breast cancer
      patients all over the world. Endoxifen is a secondary and highly active
      metabolite of tamoxifen that is formed among others by the polymorphic cytochrome
      P450 2D6 (CYP2D6). It is widely accepted that CYP2D6 poor metabolizers exert a
      pronounced decrease in endoxifen steady-state plasma concentrations compared to
      CYP2D6 extensive metabolizers. Nevertheless, an in-depth understanding of the
      chain of cause and effect between CYP2D6 genotype, endoxifen steady-state plasma
      concentration, and subsequent tamoxifen treatment benefit still remains to be
      evolved. In this study, physiologically based pharmacokinetic (PBPK)-modeling was
      applied to mechanistically investigate the impact of CYP2D6 phenotype on
      endoxifen formation in female breast cancer patients undergoing tamoxifen
      therapy. A PBPK-model of tamoxifen and its pharmacologically important
      metabolites N-desmethyltamoxifen (NDM-TAM), 4-hydroxytamoxifen (4-OH-TAM), and
      endoxifen was developed and validated. This model is able to simulate the
      pharmacokinetics (PK) after single and repeated oral tamoxifen doses in female
      breast cancer patients in dependence of the CYP2D6 phenotype. A detailed model
      based analysis of the mass balance offered support for a recent hypothesis
      stating a more prominent role for endoxifen formation from 4-OH-TAM. In the
      future this model provides a good basis to further investigate the linkage of PK,
      mode of action, and treatment outcome in dependence of factors such as phenotype,
      ethnicity, or co-treatment with CYP2D6 inhibitors.

PMID- 22661946
TI  - The evolving landscape of neurotoxicity by unconjugated bilirubin: role of glial
      cells and inflammation.
AB  - Unconjugated hyperbilirubinemia is a common condition in the first week of
      postnatal life. Although generally harmless, some neonates may develop very high
      levels of unconjugated bilirubin (UCB), which may surpass the protective
      mechanisms of the brain in preventing UCB accumulation. In this case, both short
      term and long-term neurodevelopmental disabilities, such as acute and chronic UCB
      encephalopathy, known as kernicterus, or more subtle alterations defined as
      bilirubin-induced neurological dysfunction (BIND) may be produced. There is a
      tremendous variability in babies' vulnerability toward UCB for reasons not yet
      explained, but preterm birth, sepsis, hypoxia, and hemolytic disease are
      comprised as risk factors. Therefore, UCB levels and neurological abnormalities
      are not strictly correlated. Even nowadays, the mechanisms of UCB neurotoxicity
      are still unclear, as are specific biomarkers, and little is known about lasting
      sequelae attributable to hyperbilirubinemia. On autopsy, UCB was shown to be
      within neurons, neuronal processes, and microglia, and to produce loss of
      neurons, demyelination, and gliosis. In isolated cell cultures, UCB was shown to
      impair neuronal arborization and to induce the release of pro-inflammatory
      cytokines from microglia and astrocytes. However, cell dependent sensitivity to
      UCB toxicity and the role of each nerve cell type remains not fully understood.
      This review provides a comprehensive insight into cell susceptibilities and
      molecular targets of UCB in neurons, astrocytes, and oligodendrocytes, and on
      phenotypic and functional responses of microglia to UCB. Interplay among glia
      elements and cross-talk with neurons, with a special emphasis in the UCB-induced
      immunostimulation, and the role of sepsis in BIND pathogenesis are highlighted.
      New and interesting data on the anti-inflammatory and antioxidant activities of
      different pharmacological agents are also presented, as novel and promising
      additional therapeutic approaches to BIND.

PMID- 22661949
TI  - A comprehensive review of the pharmacodynamics, pharmacokinetics, and clinical
      effects of the neutral endopeptidase inhibitor racecadotril.
AB  - Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme
      neutral endopeptidase (NEP, EC 3.4.24.11), thereby increasing exposure to NEP
      substrates including enkephalins and atrial natriuretic peptide (ANP). Upon oral
      administration racecadotril is rapidly and effectively converted into the active
      metabolite thiorphan, which does not cross the blood-brain-barrier. Racecadotril
      has mainly been tested in animal models and patients of three therapeutic areas.
      As an analgesic the effects of racecadotril across animal models were
      inconsistent. In cardiovascular diseases such as hypertension or congestive heart
      failure results from animal studies were promising, probably related to increased
      exposure to ANP, but clinical results have not shown substantial therapeutic
      benefit over existing treatment options in cardiovascular disease. In contrast,
      racecadotril was consistently effective in animal models and patients with
      various forms of acute diarrhea by inhibiting pathologic (but not basal)
      secretion from the gut without changing gastro-intestinal transit time or
      motility. This included studies in both adults and children. In direct
      comparative studies with loperamide in adults and children, racecadotril was at
      least as effective but exhibited fewer adverse events in most studies,
      particularly less rebound constipation. Several guidelines recommend the use of
      racecadotril as addition to oral rehydration treatment in children with acute
      diarrhea.

PMID- 22661950
TI  - Targeting tumor perfusion and oxygenation to improve the outcome of anticancer
      therapy.
AB  - Radiotherapy and chemotherapy are widespread clinical modalities for cancer
      treatment. Among other biological influences, hypoxia is a main factor limiting
      the efficacy of radiotherapy, primarily because oxygen is involved in the
      stabilization of the DNA damage caused by ionizing radiations. Radiobiological
      hypoxia is found in regions of rodent and human tumors with a tissue oxygenation
      level below 10 mmHg at which tumor cells become increasingly resistant to
      radiation damage. Since hypoxic tumor cells remain clonogenic, their resistance
      to the treatment strongly influences the therapeutic outcome of radiotherapy.
      There is therefore an urgent need to identify adjuvant treatment modalities aimed
      to increase tumor pO(2) at the time of radiotherapy. Since tumor hypoxia
      fundamentally results from an imbalance between oxygen delivery by poorly
      efficient blood vessels and oxygen consumption by tumor cells with high metabolic
      activities, two promising approaches are those targeting vascular reactivity and
      tumor cell respiration. This review summarizes the current knowledge about the
      development and use of tumor-selective vasodilators, inhibitors of tumor cell
      respiration, and drugs and treatments combining both activities in the context of
      tumor sensitization to X-ray radiotherapy. Tumor-selective vasodilation may also
      be used to improve the delivery of circulating anticancer agents to tumors.
      Imaging tumor perfusion and oxygenation is of importance not only for the
      development and validation of such combination treatments, but also to determine
      which patients could benefit from the therapy. Numerous techniques have been
      developed in the preclinical setting. Hence, this review also briefly describes
      both magnetic resonance and non-magnetic resonance in vivo methods and compares
      them in terms of sensitivity, quantitative or semi-quantitative properties,
      temporal, and spatial resolutions, as well as translational aspects.

PMID- 22661951
TI  - Imaging of microglia in patients with neurodegenerative disorders.
AB  - Microglia constitute the main immune defense in the central nervous system. In
      response to neuronal injury, microglia become activated, acquire phagocytic
      properties, and release a wide range of pro-inflammatory mediators that are
      essential for the annihilation of the neuronal insult. Although the role of
      microglial activation in acute neuronal damage is well defined, the
      pathophysiological processes underlying destructive or protective role to neurons
      following chronic exposure to microglial activation is still a subject of debate.
      It is likely that chronic exposure induces detrimental effects by promoting
      neuronal death through the release of neurotoxic factors. Positron emission
      tomography (PET) imaging with the use of translocator protein (TSPO) radioligands
      provides an in vivo tool for tracking the progression and severity of
      neuroinflammation in neurodegenerative disease. TSPO expression is correlated to
      the extent of microglial activation and the measurement of TSPO uptake in vivo
      with PET is a useful indicator of active disease. Although understanding of the
      interaction between radioligands and TSPO is not completely clear, there is a
      wide interest in application of TSPO imaging in neurodegenerative disease. In
      this article, we aim to review the applications of in vivo microglia imaging in
      neurodegenerative disorders such as Parkinson's disease, Huntington's disease,
      Dementias, and Multiple Sclerosis.

PMID- 22661953
TI  - Why Do We have to Move Fluid to be Able to Breathe?
AB  - The ability to breathe air represents a fundamental step in vertebrate evolution
      that was accompanied by several anatomical and physiological adaptations. The
      morphology of the air-blood barrier is highly conserved within air-breathing
      vertebrates. It is formed by three different plies, which are represented by the
      alveolar epithelium, the basal lamina, and the endothelial layer. Besides these
      conserved morphological elements, another common feature of vertebrate lungs is
      that they contain a certain amount of fluid that covers the alveolar epithelium.
      The volume and composition of the alveolar fluid is regulated by transepithelial
      ion transport mechanisms expressed in alveolar epithelial cells. These transport
      mechanisms have been reviewed extensively. Therefore, the present review focuses
      on the properties and functional significance of the alveolar fluid. How does the
      fluid enter the alveoli? What is the fate of the fluid in the alveoli? What is
      the function of the alveolar fluid in the lungs? The review highlights the
      importance of the alveolar fluid, its volume and its composition. Maintenance of
      the fluid volume and composition within certain limits is critical to facilitate
      gas exchange. We propose that the alveolar fluid is an essential element of the
      air-blood barrier. Therefore, it is appropriate to refer to this barrier as being
      formed by four plies, namely (1) the thin fluid layer covering the apical
      membrane of the epithelial cells, (2) the epithelial cell layer, (3) the basal
      membrane, and (4) the endothelial cells.

PMID- 22661952
TI  - Toll-like receptors in liver fibrosis: cellular crosstalk and mechanisms.
AB  - Toll-like receptors (TLRs) are pattern recognition receptors that distinguish
      conserved microbial products, also known as pathogen-associated molecular
      patterns (PAMPs), from host molecules. Liver is the first filter organ between
      the gastrointestinal tracts and the rest of the body through portal circulation.
      Thus, the liver is a major organ that must deal with PAMPs and microorganisms
      translocated from the intestine and to respond to the damage associated molecular
      patterns (DAMPs) released from injured organs. These PAMPs and DAMPs
      preferentially activate TLR signaling on various cell types in the liver inducing
      the production of inflammatory and fibrogenic cytokines that initiate and prolong
      liver inflammation, thereby leading to fibrosis. We summarize recent findings on
      the role of TLRs, ligands, and intracellular signaling in the pathophysiology of
      liver fibrosis due to different etiology, as well as to highlight the potential
      role of TLR signaling in liver fibrosis associated with hepatitis C infection,
      non-alcoholic and alcoholic steatoheoatitis, primary biliary cirrhosis, and
      cystic fibrosis.

PMID- 22661954
TI  - Microglial microvesicle secretion and intercellular signaling.
AB  - Microvesicles (MVs) are released from almost all cell brain types into the
      microenvironment and are emerging as a novel way of cell-to-cell communication.
      This review focuses on MVs discharged by microglial cells, the brain resident
      myeloid cells, which comprise ~10-12% of brain population. We summarize first
      evidence indicating that MV shedding is a process activated by the ATP receptor
      P2X(7) and that shed MVs represent a secretory pathway for the inflammatory
      cytokine IL-beta. We then discuss subsequent findings which clarify how IL-1 beta
      can be locally processed and released from MVs into the extracellular
      environment. In addition, we describe the current understanding about the
      mechanism of P2X(7)-dependent MV formation and membrane abscission, which, by
      involving sphingomyelinase activity and ceramide formation, may share
      similarities with exosome biogenesis. Finally we report our recent results which
      show that microglia-derived MVs can stimulate neuronal activity and participate
      to the propagation of inflammatory signals, and suggest new areas for future
      investigation.

PMID- 22661955
TI  - Impact of biofluid viscosity on size and sedimentation efficiency of the isolated
      microvesicles.
AB  - Microvesicles are nano-sized lipid vesicles released by all cells in vivo and in
      vitro. They are released physiologically under normal conditions but their rate
      of release is higher under pathological conditions such as tumors. Once released
      they end up in the systemic circulation and have been found and characterized in
      all biofluids such as plasma, serum, cerebrospinal fluid, breast milk, ascites,
      and urine. Microvesicles represent the status of the donor cell they are released
      from and they are currently under intense investigation as a potential source for
      disease biomarkers. Currently, the "gold standard" for isolating microvesicles is
      ultracentrifugation, although alternative techniques such as affinity
      purification have been explored. Viscosity is the resistance of a fluid to a
      deforming force by either shear or tensile stress. The different chemical and
      molecular compositions of biofluids have an effect on its viscosity and this
      could affect movements of the particles inside the fluid. In this manuscript we
      addressed the issue of whether viscosity has an effect on sedimentation
      efficiency of microvesicles using ultracentrifugation. We used different
      biofluids and spiked them with polystyrene beads and assessed their recovery
      using the Nanoparticle Tracking Analysis. We demonstrate that MVs recovery
      inversely correlates with viscosity and as a result, sample dilutions should be
      considered prior to ultracentrifugation when processing any biofluids.

PMID- 22661956
TI  - Animal models for investigating the central control of the Mammalian diving
      response.
AB  - Pioneering studies by Per Scholander indicated that the diving response consists
      of reflexly induced apnea, bradycardia and an alteration of blood flow that
      maintains perfusion of the heart and brain. More recently field physiological
      studies have shown that many marine animals can adjust cardiorespiratory aspects
      of their diving response depending upon the behavioral situation. This could
      suggest that the very labile heart rate during diving is under direct cortical
      control. However, the final control of autonomic nervous system functioning
      resides within the brainstem and not the cortex. Many physiologists regard the
      brain as a "black box" where important neuronal functioning occurs, but the
      complexity of such functioning leaves systematic investigation a daunting task.
      As a consequence the central control of the diving response has been under
      investigated. Thus, to further advance the field of diving physiology by
      understanding its central neuronal control, it would be first necessary to
      understand the reflex circuitry that exists within the brainstem of diving
      animals. To do this will require an appropriate animal model. In this review, two
      animals, the muskrat and rat, will be offered as animal models to investigate the
      central aspects of the diving response. Firstly, although these rodents are not
      marine animals, natural histories indicate that both animals can and do exploit
      aquatic environments. Secondly, physiological recordings during natural and
      simulated diving indicate that both animals possess the same basic physiological
      responses to underwater submersion that occur in marine animals. Thirdly, the
      size and ease of housing of both animals makes them attractive laboratory
      research animals. Finally, the enormous amount of scientific literature regarding
      rodent brainstem autonomic control mechanisms, and the availability of brain
      atlases, makes these animals ideal choices to study the central control of the
      mammalian diving response.

PMID- 22661958
TI  - Interpreting a multivariate analysis of functional neuroimaging data.

PMID- 22661957
TI  - Modulation of Neuronal Survival Factor MEF2 by Kinases in Parkinson's Disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder due
      to selective death of neurons in the substantia nigra pars compacta. The cause of
      cell death remains largely unknown. Myocyte enhancer factor 2 (MEF2) is a group
      of transcriptional factors required to regulate neuronal development, synaptic
      plasticity, as well as survival. Recent studies show that MEF2 functions are
      regulated in multiple subcellular organelles and suggest that dysregulation of
      MEF2 plays essential roles in the pathogenesis of PD. Many kinases associated
      with transcription, translation, protein misfolding, autophagy, and cellular
      energy homeostasis are involved in the neurodegenerative process. Following the
      first demonstration that mitogen-activated protein kinase p38 (p38 MAPK) directly
      phosphorylates and activates MEF2 to promote neuronal survival, several other
      kinase regulators of MEF2s have been identified. These include protein kinase A
      and extracellular signal regulated kinase 5 as positive MEF2 regulators, and
      cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3beta as negative
      regulators in response to diverse toxic signals relevant to PD. It is clear that
      MEF2 has emerged as a key point where survival and death signals converge to
      exert their regulatory effects, and dysregulation of MEF2 function in multiple
      subcellular organelles may underlie PD pathogenesis. Moreover, several other
      kinases such as leucine-rich repeat kinase 2 and PTEN-induced putative kinase 1
      (PINK1) are of particular interest due to their potential interaction with MEF2.

PMID- 22661959
TI  - Regularity extraction from non-adjacent sounds.
AB  - The regular behavior of sound sources helps us to make sense of the auditory
      environment. Regular patterns may, for instance, convey information on the
      identity of a sound source (such as the acoustic signature of a train moving on
      the rails). Yet typically, this signature overlaps in time with signals emitted
      from other sound sources. It is generally assumed that auditory regularity
      extraction cannot operate upon this mixture of signals because it only finds
      regularities between adjacent sounds. In this view, the auditory environment
      would be grouped into separate entities by means of readily available acoustic
      cues such as separation in frequency and location. Regularity extraction
      processes would then operate upon the resulting groups. Our new experimental
      evidence challenges this view. We presented two interleaved sound sequences which
      overlapped in frequency range and shared all acoustic parameters. The sequences
      only differed in their underlying regular patterns. We inserted deviants into one
      of the sequences to probe whether the regularity was extracted. In the first
      experiment, we found that these deviants elicited the mismatch negativity (MMN)
      component. Thus the auditory system was able to find the regularity between the
      non-adjacent sounds. Regularity extraction was not influenced by sequence
      cohesiveness as manipulated by the relative duration of tones and silent inter
      tone-intervals. In the second experiment, we showed that a regularity connecting
      non-adjacent sounds was discovered only when the intervening sequence also
      contained a regular pattern, but not when the intervening sounds were randomly
      varying. This suggests that separate regular patterns are available to the
      auditory system as a cue for identifying signals coming from distinct sound
      sources. Thus auditory regularity extraction is not necessarily confined to a
      processing stage after initial sound grouping, but may precede grouping when
      other acoustic cues are unavailable.

PMID- 22661960
TI  - Impulsivity and rapid decision-making for reward.
AB  - Impulsivity is a feature of many brain disorders. Although often defined as the
      predisposition to act with an inadequate degree of deliberation, forethought, or
      control, it has proven difficult to measure. This may in part be due to the fact
      that it is a multifaceted construct, with impulsive decisions potentially arising
      as a result of a number of underlying mechanisms. Indeed, a "functional" degree
      of impulsivity may even promote effective behavior in healthy participants in a
      way that can be advantageous under certain circumstances. Although many tasks
      have been developed to study impulsivity, few examine decisions made rapidly, for
      time-sensitive rewards. In the current study we examine behavior in 59 adults on
      a manual "Traffic Light" task which requires participants to take risks under
      time pressure, if they are to maximize reward. We show that behavioral variables
      that index rapid anticipatory responding in this paradigm are correlated with
      one, specific self-report measure of impulsivity: "lack of premeditation" on the
      UPPS Impulsive Behavior Scale. Participants who scored more highly on this
      subscale performed better on the task. Moreover, anticipatory behavior reduced
      significantly with age (18-79 years), an effect that continued to be upheld after
      correction for potential age differences in the ability to judge the timing of
      responses. Based on these findings, we argue that the Traffic Light task provides
      a parametric method to study one aspect of impulsivity in health and disease:
      namely, rapid decision-making in pursuit of risky, time-sensitive rewards.

PMID- 22661961
TI  - Effect of orthographic processes on letter identity and letter-position encoding
      in dyslexic children.
AB  - The ability to identify letters and encode their position is a crucial step of
      the word recognition process. However and despite their word identification
      problem, the ability of dyslexic children to encode letter identity and letter
      position within strings was not systematically investigated. This study aimed at
      filling this gap and further explored how letter identity and letter-position
      encoding is modulated by letter context in developmental dyslexia. For this
      purpose, a letter-string comparison task was administered to French dyslexic
      children and two chronological age (CA) and reading age (RA)-matched control
      groups. Children had to judge whether two successively and briefly presented four
      letter strings were identical or different. Letter-position and letter identity
      were manipulated through the transposition (e.g., RTGM vs. RMGT) or substitution
      of two letters (e.g., TSHF vs. TGHD). Non-words, pseudo-words, and words were
      used as stimuli to investigate sub-lexical and lexical effects on letter
      encoding. Dyslexic children showed both substitution and transposition detection
      problems relative to CA-controls. A substitution advantage over transpositions
      was only found for words in dyslexic children whereas it extended to pseudo-words
      in RA-controls and to all type of items in CA-controls. Letters were better
      identified in the dyslexic group when belonging to orthographically familiar
      strings. Letter-position encoding was very impaired in dyslexic children who did
      not show any word context effect in contrast to CA-controls. Overall, the current
      findings point to a strong letter identity and letter-position encoding disorder
      in developmental dyslexia.

PMID- 22661962
TI  - The benefits of executive control training and the implications for language
      processing.
AB  - Recent psycholinguistics research suggests that the executive function (EF) skill
      known as conflict resolution - the ability to adjust behavior in the service of
      resolving among incompatible representations - is important for several language
      processing tasks such as lexical and syntactic ambiguity resolution, verbal
      fluency, and common-ground assessment. Here, we discuss work showing that various
      EF skills can be enhanced through consistent practice with working-memory tasks
      that tap these EFs, and, moreover, that improvements on the training tasks
      transfer across domains to novel tasks that may rely on shared underlying EFs.
      These findings have implications for language processing and could launch new
      research exploring if EF training, within a "process-specific" framework, could
      be used as a remediation tool for improving general language use. Indeed, work in
      our lab demonstrates that EF training that increases conflict-resolution
      processes has selective benefits on an untrained sentence-processing task
      requiring syntactic ambiguity resolution, which relies on shared conflict
      resolution functions. Given claims that conflict-resolution abilities contribute
      to a range of linguistic skills, EF training targeting this process could
      theoretically yield wider performance gains beyond garden-path recovery. We offer
      some hypotheses on the potential benefits of EF training as a component of
      interventions to mitigate general difficulties in language processing. However,
      there are caveats to consider as well, which we also address.

PMID- 22661963
TI  - Social cognition in williams syndrome: genotype/phenotype insights from partial
      deletion patients.
AB  - Identifying genotype/phenotype relations in human social cognition has been
      enhanced by the study of Williams syndrome (WS). Indeed, individuals with WS
      present with a particularly strong social drive, and researchers have sought to
      link deleted genes in the WS critical region (WSCR) of chromosome 7q11.23 to this
      unusual social profile. In this paper, we provide details of two case studies of
      children with partial genetic deletions in the WSCR: an 11-year-old female with a
      deletion of 24 of the 28 WS genes, and a 14-year-old male who presents with the
      opposite profile, i.e., the deletion of only four genes at the telomeric end of
      the WSCR. We tested these two children on a large battery of standardized and
      experimental social perception and social cognition tasks - both implicit and
      explicit - as well as standardized social questionnaires and general psychometric
      measures. Our findings reveal a partial WS socio-cognitive profile in the female,
      contrasted with a more autistic-like profile in the male. We discuss the
      implications of these findings for genotype/phenotype relations, as well as the
      advantages and limitations of animal models and of case study approaches.

PMID- 22661964
TI  - Task-related, low-frequency task-residual, and resting state activity in the
      default mode network brain regions.
AB  - The hypothesis of a default mode network (DMN) of brain function is based on
      observations of task-independent decreases of brain activity during effort as
      participants are engaged in tasks in contrast to resting. On the other hand,
      studies also showed that DMN regions activate rather than deactivate in response
      to task-related events. Thus, does DMN "deactivate" during effort as compared to
      resting? We hypothesized that, with high-frequency event-related signals removed,
      the task-residual activities of the DMN would decrease as compared to resting. We
      addressed this hypothesis with two approaches. First, we examined DMN activities
      during resting, task residuals, and task conditions in the stop signal task using
      independent component analysis (ICA). Second, we compared the fractional
      amplitude of low-frequency fluctuation (fALFF) signals of DMN in resting, task
      residuals, and task data. In the results of ICA of 76 subjects, the precuneus and
      posterior cingulate cortex (PCC) showed increased activation during task as
      compared to resting and task residuals, indicating DMN responses to task events.
      Precuneus but not the PCC showed decreased activity during task residual as
      compared to resting. The latter finding was mirrored by fALFF, which is decreased
      in the precuneus during task residuals, as compared to resting and task. These
      results suggested that the low-frequency blood oxygen level-dependent signals of
      the precuneus may represent a useful index of effort during cognitive
      performance.

PMID- 22661965
TI  - Gender differences in cerebral aneurysm location.
AB  - BACKGROUND AND PURPOSE: A limited number of studies consisting predominantly of
      ruptured aneurysms have looked at differences in anatomical distribution of
      aneurysms between male and females. Unlike all other causes of stroke,
      subarachnoid hemorrhages (SAH) occur more often in women and are thought to be a
      result of both hormonal influences and variation in wall shear stress. This paper
      retrospectively looks at a cohort of largely unruptured intracranial aneurysms to
      determine if there exists a gender discrepancy in the anatomic distribution of
      cerebral aneurysms. METHODS: A retrospective review of consecutive patients with
      ruptured and unruptured intradural saccular cerebral aneurysms treated
      endovascularly was performed. RESULTS: Six hundred eighty-two aneurysms were
      treated. Seventy-two percentage of the patients were women and 27% of patients
      presented with SAH. Among women, most aneurysms were located along the ICA (54%)
      while men the ACA (29%, compared to 15% in women), a discrepancy evident in both
      unruptured and ruptured groups. Females tended to present later in life (59 vs.
      55 years), with multiple aneurysms (11 vs. 6% in men), and with SAH (28 vs. 23%
      in men) - the majority of these ruptured aneurysms were located at the ICA (42%),
      while men at the ACA (47%). Additionally, the majority (68%) of ruptured ICA
      aneurysms were PCOM. CONCLUSION: Understanding the natural history of aneurysms
      is imperative in treating incidentally found aneurysms. Significant differences
      exist between the genders in relation to aneurysm location, the most pronounced
      at the ICA and ACA. Previously described hormonal and hemodynamic theories behind
      cerebral aneurysm pathogenesis seem like plausible reasons to explain these
      differences.

PMID- 22661966
TI  - Translating basic science research to clinical application: models and strategies
      for intracerebral hemorrhage.
AB  - Preclinical stroke models provide insights into mechanisms of cellular injury and
      potential therapeutic targets. Renewed efforts to standardize preclinical
      practices and adopt more rigorous approaches reflect the assumption that a better
      class of compounds will translate into clinical efficacy. While the need for
      novel therapeutics is clear, it is also critical that diagnostics be improved to
      allow for more rapid treatment upon hospital admission. Advances in imaging
      techniques have aided in the diagnosis of stroke, yet current limitations and
      expenses demonstrate the need for new and complementary approaches. Intracerebral
      hemorrhage (ICH) exhibits the highest mortality rate, displays unique pathology
      and requires specialized treatment strategies relative to other forms of stroke.
      The aggressive nature and severe consequences of ICH underscore the need for
      novel therapeutic approaches as well as accurate and expeditious diagnostic
      tools. The use of experimental models will continue to aid in addressing these
      important issues as the field attempts to translate basic science findings into
      the clinical setting. Several preclinical models of ICH have been developed and
      are widely used to recapitulate human pathology. Because each model has
      limitations, the burden lies with the investigator to clearly define the question
      being asked and select the model system that is most relevant to that question.
      It may also be necessary to optimize and refine pre-existing paradigms, or
      generate new paradigms, as the future success of translational research is
      dependent upon the ability to mimic human sequelae and assess clinically relevant
      outcome measures as means to evaluate therapeutic efficacy.

PMID- 22661967
TI  - Sleep apnea syndrome and cognition.
AB  - Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized
      by repetitive episodes of airflow cessation resulting in brief arousals and
      intermittent hypoxemia. Several studies have documented significant daytime
      cognitive and behavioral dysfunction that seems to extend beyond that associated
      with simple sleepiness and that persists in some patients after therapeutic
      intervention. A still unanswered question is whether cognitive symptoms in OSA
      are primarily a consequence of sleep fragmentation and hypoxemia, or whether they
      coexist independently from OSA. Moreover, very little is known about OSA effects
      on cognitive performances in the elderly in whom an increased prevalence of OSA
      is present. In this review we will consider recent reports in the association
      between sleep apnea and cognition, with specific interest in elderly subjects, in
      whom sleep disturbances and age-related cognitive decline naturally occur. This
      will allow us to elucidate the behavioral and cognitive functions in OSA patients
      and to gain insight into age differences in the cognitive impairment. Clinically,
      these outcomes will aid clinicians in the evaluation of diurnal consequences of
      OSA and the need to propose early treatment.

PMID- 22661969
TI  - Hypoglycemia in type 2 diabetes: current controversies and changing practices.
AB  - Hypoglycemia is well-recognized to limit the degree of glycemic control possible
      for many individuals for diabetes. Although the likelihood of hypoglycemia
      increases as A1c levels decrease in type 1 diabetes, insulin-treated type 2
      diabetic persons with higher A1c appear paradoxically to have more hypoglycemia
      which may explain, in part, the adverse outcome reported in the ACCORD study.
      Approaches to glucose-lowering that cause lesser degrees of risk for
      hypoglycemia, technologies to better ascertain hypoglycemic events, and better
      understanding of patient characteristics associated with greater likelihood of
      hypoglycemia will all be required to reduce this limiting factor in optimizing
      glycemic treatment.

PMID- 22661968
TI  - Circadian control of neuroendocrine circuits regulating female reproductive
      function.
AB  - Female reproduction requires the precise temporal organization of interacting,
      estradiol-sensitive neural circuits that converge to optimally drive hypothalamo
      pituitary-gonadal (HPG) axis functioning. In mammals, the master circadian
      pacemaker in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus
      coordinates reproductively relevant neuroendocrine events necessary to maximize
      reproductive success. Likewise, in species where periods of fertility are brief,
      circadian oversight of reproductive function ensures that estradiol-dependent
      increases in sexual motivation coincide with ovulation. Across species, including
      humans, disruptions to circadian timing (e.g., through rotating shift work, night
      shift work, poor sleep hygiene) lead to pronounced deficits in ovulation and
      fecundity. Despite the well-established roles for the circadian system in female
      reproductive functioning, the specific neural circuits and neurochemical
      mediators underlying these interactions are not fully understood. Most work to
      date has focused on the direct and indirect communication from the SCN to the
      gonadotropin-releasing hormone (GnRH) system in control of the preovulatory
      luteinizing hormone (LH) surge. However, the same clock genes underlying
      circadian rhythms at the cellular level in SCN cells are also common to target
      cell populations of the SCN, including the GnRH neuronal network. Exploring the
      means by which the master clock synergizes with subordinate clocks in GnRH cells
      and its upstream modulatory systems represents an exciting opportunity to further
      understand the role of endogenous timing systems in female reproduction. Herein
      we provide an overview of the state of knowledge regarding interactions between
      the circadian timing system and estradiol-sensitive neural circuits driving GnRH
      secretion and the preovulatory LH surge.

PMID- 22661971
TI  - Prostate cancer - a biomarker perspective.
AB  - Despite early detection and reduced risk of death, prostate cancer still remains
      the second leading cause of cancer death in American men. There is currently no
      cure for advanced prostate cancer. The multistage, stochastic and highly
      heterogeneous nature of prostate cancer, coupled with genetic and epigenetic
      alterations that occur during disease progression and response to therapy,
      represent fundamental challenges in our quest to understand and control this
      complex and prevalent disease. Recent advances in drug development and
      breakthroughs in omics technologies have renewed our efforts to identify novel
      biomarkers for prostate cancer prognosis, prediction, and therapeutic response
      monitoring. In this perspective article, we overview the current status and
      highlight future prospects of biomarkers for prostate cancer, a disease that
      affects millions of men worldwide.

PMID- 22661972
TI  - Complete Genome of Ignavibacterium album, a Metabolically Versatile, Flagellated,
      Facultative Anaerobe from the Phylum Chlorobi.
AB  - Prior to the recent discovery of Ignavibacterium album (I. album), anaerobic
      photoautotrophic green sulfur bacteria (GSB) were the only members of the
      bacterial phylum Chlorobi that had been grown axenically. In contrast to GSB,
      sequence analysis of the 3.7-Mbp genome of I. album shows that this recently
      described member of the phylum Chlorobi is a chemoheterotroph with a versatile
      metabolism. I. album lacks genes for photosynthesis and sulfur oxidation but has
      a full set of genes for flagella and chemotaxis. The occurrence of genes for
      multiple electron transfer complexes suggests that I. album is capable of
      organoheterotrophy under both oxic and anoxic conditions. The occurrence of genes
      encoding enzymes for CO(2) fixation as well as other enzymes of the reductive TCA
      cycle suggests that mixotrophy may be possible under certain growth conditions.
      However, known biosynthetic pathways for several amino acids are incomplete; this
      suggests that I. album is dependent upon on exogenous sources of these
      metabolites or employs novel biosynthetic pathways. Comparisons of I. album and
      other members of the phylum Chlorobi suggest that the physiology of the ancestors
      of this phylum might have been quite different from that of modern GSB.

PMID- 22661973
TI  - Visualizing evolution in real-time method for strain engineering.
AB  - The adaptive landscape for an industrially relevant phenotype is determined by
      the effects of the genetic determinants on the fitness of the microbial system.
      Identifying the underlying adaptive landscape for a particular phenotype of
      interest will greatly enhance our abilities to engineer more robust microbial
      strains. Visualizing evolution in real-time (VERT) is a recently developed method
      based on in vitro adaptive evolution that facilitates the identification of
      fitter mutants throughout the course of evolution. Combined with high-throughput
      genomic tools, VERT can greatly enhance the mapping of adaptive landscapes of
      industrially relevant phenotypes in microbial systems, thereby expanding our
      knowledge on the parameters that can be used for strain engineering.

PMID- 22661970
TI  - Intracellular signal transduction and modification of the tumor microenvironment
      induced by RET/PTCs in papillary thyroid carcinoma.
AB  - RET gene rearrangements (RET/PTCs) represent together with BRAF point mutations
      the two major groups of mutations involved in papillary thyroid carcinoma (PTC)
      initiation and progression. In this review, we will examine the mechanisms
      involved in RET/PTC-induced thyroid cell transformation. In detail, we will
      summarize the data on the molecular mechanisms involved in RET/PTC formation and
      in its function as a dominant oncogene, on the activated signal transduction
      pathways and on the induced gene expression modifications. Moreover, we will
      report on the effects of RET/PTCs on the tumor microenvironment. Finally, a short
      review of the literature on RET/PTC prognostic significance will be presented.

PMID- 22661974
TI  - Biomarkers for exposure to sand flies bites as tools to aid control of
      leishmaniasis.
AB  - Intense research efforts so far have not been sufficient to reduce leishmaniasis
      burden worldwide. This disease is transmitted by bites of infected sand flies,
      which inject saliva in the host skin in an attempt to obtain a blood meal. Sand
      fly saliva has an array of proteins with diverse pharmacological properties that
      modulates the host homeostatic and immune responses. Some of these proteins are
      also immunogenic and can induce both cellular and humoral immune responses.
      Recently, the use of sand fly salivary proteins to estimate exposure to sand fly
      bites and consequently the risk of infection has emerged. Here, we review
      evidence that supports the use of the host immune responses against sand fly
      salivary proteins to estimate risk of infection. We also discuss how the use of
      recombinant salivary proteins can optimize serological surveys and provide
      guidance for the implementation of specific measures for disease control in
      endemic areas.

PMID- 22661976
TI  - Evolutionary and structural perspectives of plant cyclic nucleotide-gated cation
      channels.
AB  - Ligand-gated cation channels are a frequent component of signaling cascades in
      eukaryotes. Eukaryotes contain numerous diverse gene families encoding ion
      channels, some of which are shared and some of which are unique to particular
      kingdoms. Among the many different types are cyclic nucleotide-gated channels
      (CNGCs). CNGCs are cation channels with varying degrees of ion conduction
      selectivity. They are implicated in numerous signaling pathways and permit
      diffusion of divalent and monovalent cations, including Ca(2+) and K(+). CNGCs
      are present in both plant and animal cells, typically in the plasma membrane;
      recent studies have also documented their presence in prokaryotes. All eukaryote
      CNGC polypeptides have a cyclic nucleotide-binding domain and a calmodulin
      binding domain as well as a six transmembrane/one pore tertiary structure. This
      review summarizes existing knowledge about the functional domains present in
      these cation-conducting channels, and considers the evidence indicating that
      plant and animal CNGCs evolved separately. Additionally, an amino acid motif that
      is only found in the phosphate binding cassette and hinge regions of plant CNGCs,
      and is present in all experimentally confirmed CNGCs but no other channels was
      identified. This CNGC-specific amino acid motif provides an additional diagnostic
      tool to identify plant CNGCs, and can increase confidence in the annotation of
      open reading frames in newly sequenced genomes as putative CNGCs. Conversely, the
      absence of the motif in some plant sequences currently identified as probable
      CNGCs may suggest that they are misannotated or protein fragments.

PMID- 22661977
TI  - Stiff mutant genes of phycomyces affect turgor pressure and wall mechanical
      properties to regulate elongation growth rate.
AB  - Regulation of cell growth is paramount to all living organisms. In plants, algae
      and fungi, regulation of expansive growth of cells is required for development
      and morphogenesis. Also, many sensory responses of stage IVb sporangiophores of
      Phycomyces blakesleeanus are produced by regulating elongation growth rate
      (growth responses) and differential elongation growth rate (tropic responses).
      "Stiff" mutant sporangiophores exhibit diminished tropic responses and are found
      to be defective in at least five genes; madD, E, F, G, and J. Prior experimental
      research suggests that the defective genes affect growth regulation, but this was
      not verified. All the growth of the single-celled stalk of the stage IVb
      sporangiophore occurs in a short region termed the "growth zone." Prior
      experimental and theoretical research indicates that elongation growth rate of
      the stage IVb sporangiophore can be regulated by controlling the cell wall
      mechanical properties within the growth zone and the magnitude of the turgor
      pressure. A quantitative biophysical model for elongation growth rate is required
      to elucidate the relationship between wall mechanical properties and turgor
      pressure during growth regulation. In this study, it is hypothesized that the
      mechanical properties of the wall within the growth zone of stiff mutant
      sporangiophores are different compared to wild type (WT). A biophysical equation
      for elongation growth rate is derived for fungal and plant cells with a growth
      zone. Two strains of stiff mutants are studied, C149 madD120 (-) and C216 geo- (
      ). Experimental results demonstrate that turgor pressure is larger but
      irreversible wall deformation rates within the growth zone and growth zone length
      are smaller for stiff mutant sporangiophores compared to WT. These findings can
      explain the diminished tropic responses of the stiff mutant sporangiophores. It
      is speculated that the defective genes affect the amount of wall-building
      material delivered to the inner cell wall.

PMID- 22661975
TI  - Protective immunity and vaccination against cutaneous leishmaniasis.
AB  - Although a great deal of knowledge has been gained from studies on the
      immunobiology of leishmaniasis, there is still no universally acceptable, safe,
      and effective vaccine against the disease. This strongly suggests that we still
      do not completely understand the factors that control and/or regulate the
      development and sustenance of anti-Leishmania immunity, particularly those
      associated with secondary (memory) immunity. Such an understanding is critically
      important for designing safe, effective, and universally acceptable vaccine
      against the disease. Here we review the literature on the correlate of protective
      anti-Leishmania immunity and vaccination strategies against leishmaniasis with a
      bias emphasis on experimental cutaneous leishmaniasis.

PMID- 22661978
TI  - Comparison of tissue heat balance- and thermal dissipation-derived sap flow
      measurements in ring-porous oaks and a pine.
AB  - Sap flow measurements have become integral in many physiological and ecological
      investigations. A number of methods are used to estimate sap flow rates in trees,
      but probably the most popular is the thermal dissipation (TD) method because of
      its affordability, relatively low power consumption, and ease of use. However,
      there have been questions about the use of this method in ring-porous species and
      whether individual species and site calibrations are needed. We made concurrent
      measurements of sap flow rates using TD sensors and the tissue heat balance (THB)
      method in two oak species (Quercus prinus Willd. and Quercus velutina Lam.) and
      one pine (Pinus echinata Mill.). We also made concurrent measurements of sap flow
      rates using both 1 and 2-cm long TD sensors in both oak species. We found that
      both the TD and THB systems tended to match well in the pine individual, but sap
      flow rates were underestimated by 2-cm long TD sensors in five individuals of the
      two ring-porous oak species. Underestimations of 20-35% occurred in Q. prinus
      even when a "Clearwater" correction was applied to account for the shallowness of
      the sapwood depth relative to the sensor length and flow rates were
      underestimated by up to 50% in Q. velutina. Two centimeter long TD sensors also
      underestimated flow rates compared with 1-cm long sensors in Q. prinus, but only
      at large flow rates. When 2-cm long sensor data in Q. prinus were scaled using
      the regression with 1-cm long data, daily flow rates matched well with the rates
      measured by the THB system. Daily plot level transpiration estimated using TD sap
      flow rates and scaled 1 cm sensor data averaged about 15% lower than those
      estimated by the THB method. Therefore, these results suggest that 1-cm long
      sensors are appropriate in species with shallow sapwood, however more corrections
      may be necessary in ring-porous species.

PMID- 22661979
TI  - Cotton fiber: a powerful single-cell model for cell wall and cellulose research.
AB  - Cotton fibers are single-celled extensions of the seed epidermis. They can be
      isolated in pure form as they undergo staged differentiation including primary
      cell wall synthesis during elongation and nearly pure cellulose synthesis during
      secondary wall thickening. This combination of features supports clear
      interpretation of data about cell walls and cellulose synthesis in the context of
      high throughput modern experimental technologies. Prior contributions of cotton
      fiber to building fundamental knowledge about cell walls will be summarized and
      the dynamic changes in cell wall polymers throughout cotton fiber differentiation
      will be described. Recent successes in using stable cotton transformation to
      alter cotton fiber cell wall properties as well as cotton fiber quality will be
      discussed. Futurec prospects to perform experiments more rapidly through altering
      cotton fiberwall properties via virus-induced gene silencing will be evaluated.

PMID- 22661980
TI  - MicroRNAs as regulators in plant metal toxicity response.
AB  - Metal toxicity is a major stress affecting crop production. This includes metals
      that are essential for plants (copper, iron, zinc, manganese), and non-essential
      metals (cadmium, aluminum, cobalt, mercury). A primary common effect of high
      concentrations of metal such as aluminum, copper, cadmium, or mercury is root
      growth inhibition. Metal toxicity triggers the accumulation of reactive oxygen
      species leading to damage of lipids, proteins, and DNA. The plants response to
      metal toxicity involves several biological processes that require fine and
      precise regulation at transcriptional and post-transcriptional levels. MicroRNAs
      (miRNAs) are 21 nucleotide non-coding RNAs that regulate gene expression at the
      post-transcriptional level. A miRNA, incorporated into a RNA-induced silencing
      complex, promotes cleavage of its target mRNA that is recognized by an almost
      perfect base complementarity. In plants, miRNA regulation is involved in
      development and also in biotic and abiotic stress responses. We review novel
      advances in identifying miRNAs related to metal toxicity responses and their
      potential role according to their targets. Most of the targets for plant metal
      responsive miRNAs are transcription factors. Information about metal-responsive
      miRNAs in different plants points to important regulatory roles of miR319,
      miR390, miR393, and miR398. The target of miR319 is the TCP transcription factor,
      implicated in growth control. miR390 exerts its action through the biogenesis of
      trans-acting small interference RNAs that, in turn, regulate auxin responsive
      factors. miR393 targets the auxin receptors TIR1/AFBs and a bHLH transcription
      factor. Increasing evidence points to the crucial role of miR398 and its targets
      Cu/Zn superoxide dismutases in the control of the oxidative stress generated
      after high copper or iron exposure.

PMID- 22661982
TI  - Soybean Proteome Database 2012: update on the comprehensive data repository for
      soybean proteomics.
AB  - The Soybean Proteome Database (SPD) was created to provide a data repository for
      functional analyses of soybean responses to flooding stress, thought to be a
      major constraint for establishment and production of this plant. Since the last
      publication of the SPD, we thoroughly enhanced the contents of database,
      particularly protein samples and their annotations from several organelles. The
      current release contains 23 reference maps of soybean (Glycine max cv. Enrei)
      proteins collected from several organs, tissues, and organelles including the
      maps for plasma membrane, cell wall, chloroplast, and mitochondrion, which were
      analyzed by two-dimensional polyacrylamide gels. Furthermore, the proteins
      analyzed with gel-free proteomics technique have been added and are available
      online. In addition to protein fluctuations under flooding, those of salt and
      drought stress have been included in the current release. A case analysis
      employing a portion of those newly released data was conducted, and the results
      will be shown. An 'omics table has also been provided to reveal relationships
      among mRNAs, proteins, and metabolites with a unified temporal-profile tag in
      order to facilitate retrieval of the data based on the temporal profiles. An
      intuitive user interface based on dynamic HTML enables users to browse the
      network as well as the profiles of the multiple "omes" in an integrated fashion.
      The SPD is available at: http://proteome.dc.affrc.go.jp/Soybean/

PMID- 22661981
TI  - Genome-Wide Characterization of ISR Induced in Arabidopsis thaliana by
      Trichoderma hamatum T382 Against Botrytis cinerea Infection.
AB  - In this study, the molecular basis of the induced systemic resistance (ISR) in
      Arabidopsis thaliana by the biocontrol fungus Trichoderma hamatum T382 against
      the phytopathogen Botrytis cinerea B05-10 was unraveled by microarray analysis
      both before (ISR-prime) and after (ISR-boost) additional pathogen inoculation.
      The observed high numbers of differentially expressed genes allowed us to
      classify them according to the biological pathways in which they are involved. By
      focusing on pathways instead of genes, a holistic picture of the mechanisms
      underlying ISR emerged. In general, a close resemblance is observed between ISR
      prime and systemic acquired resistance, the systemic defense response that is
      triggered in plants upon pathogen infection leading to increased resistance
      toward secondary infections. Treatment with T. hamatum T382 primes the plant (ISR
      prime), resulting in an accelerated activation of the defense response against B.
      cinerea during ISR-boost and a subsequent moderation of the B. cinerea induced
      defense response. Microarray results were validated for representative genes by
      qRT-PCR. The involvement of various defense-related pathways was confirmed by
      phenotypic analysis of mutants affected in these pathways, thereby proving the
      validity of our approach. Combined with additional anthocyanin analysis data
      these results all point to the involvement of the phenylpropanoid pathway in T.
      hamatum T382-induced ISR.

PMID- 22661983
TI  - Divergence and Redundancy in CSLD2 and CSLD3 Function During Arabidopsis Thaliana
      Root Hair and Female Gametophyte Development.
AB  - The Arabidopsis cellulose synthase-like D (CSLD) 2 and 3 genes are known to
      function in root hair development. Here, we show that these genes also play a
      role in female gametophyte development because csld2 csld3 double mutants were
      observed to have low seed set that could be traced to defects in female
      transmission efficiency. Cell biological studies of csld2 csld3 ovules showed
      synergid cell degeneration during megagametogenesis and reduced pollen tube
      penetration during fertilization. Although CSLD2 and CSLD3 function redundantly
      in female gametophyte development, detailed analyses of root hair phenotypes of
      progeny from genetic crosses between csld2 and csld3, suggest that CSLD3 might
      play a more prominent role than CSLD2 in root hair development. Phylogenetic and
      gene duplication studies of CSLD2 and CSLD3 homologs in Arabidopsis lyrata,
      Populus, Medicago, maize, and Physcomitrella were further performed to
      investigate the course of evolution for these genes. Our analyses indicate that
      the ancestor of land plants possibly contained two copies of CSLD genes, one of
      which developed into the CSLD5 lineage in flowering plants, and the other formed
      the CSLD1/2/3/4 clade. In addition, CSLD2 and CSLD3 likely originated from a
      recent genome-wide duplication event explaining their redundancy. Moreover,
      sliding-window dN/dS analysis showed that most of the coding regions of CSLD2 and
      CSLD3 have been under strong purifying selection pressure. However, the region
      that encodes the N-terminus of CSLD3 has been under relatively relaxed selection
      pressure as indicated by its high dN/dS value, suggesting that CSLD3 might have
      gained additional functions through more frequent non-synonymous sequence changes
      at the N-terminus, which could partly explain the more prominent role of CSLD3
      during root hair development compared to CSLD2.

PMID- 22661985
TI  - Integration of next-generation sequencing based multi-omics approaches in
      toxicogenomics.

PMID- 22661984
TI  - Dynamic modeling of genes controlling cancer stem cell proliferation.
AB  - The growing evidence that cancer originates from stem cells (SC) holds a great
      promise to eliminate this disease by designing specific drug therapies for
      removing cancer SC. Translation of this knowledge into predictive tests for the
      clinic is hampered due to the lack of methods to discriminate cancer SC from non
      cancer SC. Here, we address this issue by describing a conceptual strategy for
      identifying the genetic origins of cancer SC. The strategy incorporates a high
      dimensional group of differential equations that characterizes the proliferation,
      differentiation, and reprogramming of cancer SC in a dynamic cellular and
      molecular system. The deployment of robust mathematical models will help uncover
      and explain many still unknown aspects of cell behavior, tissue function, and
      network organization related to the formation and division of cancer SC. The
      statistical method developed allows biologically meaningful hypotheses about the
      genetic control mechanisms of carcinogenesis and metastasis to be tested in a
      quantitative manner.

PMID- 22661986
TI  - Genomic "dark matter": implications for understanding human disease mechanisms,
      diagnostics, and cures.

PMID- 22661987
TI  - Risk factors for breast cancer in China: similarities and differences with
      western populations.

PMID- 22661988
TI  - Bioinformatics characterization of differential proteins in serum of mothers
      carrying Down syndrome fetuses: combining bioinformatics and ELISA.
AB  - INTRODUCTION: Characterization of novel proteins in maternal serum derived from
      mothers carrying Down syndrome (DS) fetuses. MATERIAL AND METHODS: Based on last
      comparative proteomic analysis, five significant differences of expressed
      proteins in serum from four groups have been confirmed by ELISA. DAVID and GeneGo
      MetaCore were used to bioinformatically analyze candidate protein markers.
      RESULTS: The serum levels of ceruloplasmin (CP) and complement factor B (CFB)
      were significantly increased in mother carried DS fetuses (346.5 ng/ml and 466.8
      ng/ml vs. 248.6 ng/ml and 293.5 ng/ml, p< 0.05). Twenty-nine proteins were mainly
      categorized into binding, catalytic activity and enzyme regulator activity
      proteins, and their biological roles were involved in biological regulation,
      metabolic processes, cellular processes, and response to stimuli. The immune
      response alternative complement pathway was the most significant GeneGo Pathway
      related to DS. CONCLUSIONS: These 29 proteins have relations with the development
      of Down syndrome, especially CP and CFB play more important roles.

PMID- 22661989
TI  - Effect of palmitic acid and linoleic acid on expression of ICAM-1 and VCAM-1 in
      human bone marrow endothelial cells (HBMECs).
AB  - INTRODUCTION: The amount and type of fatty acids (FAs) in the diet influence the
      risk of atherosclerosis. Palmitic acid and linoleic acid exist at high levels in
      Iranian edible oils. In this study, we investigated the effect of palmitic acid
      and linoleic acid on expression of soluble and cell-associated forms of
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) in human bone marrow endothelial cells (HBMECs). MATERIAL AND METHODS:
      The endothelial cells were induced with bacterial lipopolysaccharide (LPS) or
      tumor necrosis factor alpha (TNF-alpha), and thereafter incubated with palmitic
      or linoleic acid. The level of soluble and cell-associated VCAM-1 and ICAM-1 were
      analyzed using ELISA and western blot. RESULTS: Our findings indicated that
      palmitic acid up-regulates the expression of ICAM-1 and VCAM-1 in HBMECs when
      these cells are induced with TNF-alpha or LPS. In addition, the results suggest
      that linoleic acid could sustain up-regulated ICAM-1 and VCAM-1 in activated
      endothelial cells. CONCLUSIONS: Chronic activation of endothelial cells in the
      presence of palmitic and linoleic may account for pathogenesis of cardiovascular
      events. These findings provide further support for the detrimental effects of
      these fatty acids, especially palmitic acid, in promotion and induction of
      cardiovascular diseases which are prevalent in the Iranian population.

PMID- 22661990
TI  - The effect of adhesive strength of hydroxyapatite coating on the stability of
      hydroxyapatite-coated prostheses in vivo at the early stage of implantation.
AB  - INTRODUCTION: With the increase in joint revision surgery after arthroplasty,
      defects of hydroxyapatite (HA)-coated prostheses have been observed increasingly
      often. These defects adversely affect the prosthetic stability in vivo. This
      study has analyzed the potential effect of the adhesive strength of HA coating on
      the stability of HA-coated prostheses in vivo after its implantation. MATERIAL
      AND METHODS: Sixty experimental rabbits were divided into HA- and Ti-coated
      groups. HA-coated prostheses were implanted into the bilateral epicondyle of
      rabbits femurs. Ti-coated prostheses were implanted as control. At different time
      points(4, 9, and 15 weeks) after implantation, bone tissue samples were fetched
      out respectively for histomorphometric analysis. Push-out testing was used to
      detect the ultimate shear strength at the bone-prosthesis interface. Scanning
      electron microscope (SEM) observation and energy-dispersive X-ray spectroscopy
      (EDX) analysis were used to observe the changes in surface composition of the
      prostheses after the ultimate shear strength testing. The coating adhesive
      strength of two kinds of coatings were also examined by scratch testing. RESULTS:
      Hydroxyapatite coating has an obvious advantage in facilitating osteogenesis and
      its plays a critical role in the stability of prostheses. However, the ultimate
      shear strength of HA-coated prostheses is much lower than that of Ti-coated
      implants (p < 0.01). Further study has demonstrated that the stability of HA
      coated prostheses in vivo is affected by the relatively low adhesive strength
      between coating and substrate. CONCLUSIONS: Obvious advantage in facilitating
      osteogenesis around HA-coated prostheses is not the only factor that determines
      the stability of prostheses in vivo.

PMID- 22661991
TI  - Anthropometric indices in relation to overweight and obesity among Turkish
      medical students.
AB  - INTRODUCTION: The aim of this study was to present the reference anthropometric
      data associated with obesity for cardiovascular risk and metabolic diseases for
      healthy young adults in a Turkish population. MATERIAL AND METHODS: The study
      group consisted of 1163 second-year medical students (650 women, 513 men) aged 20
      25 years from Cukurova University in Adana and the measurements were made using a
      flexible standard measuring tape. The data were collected during the period 2007
      2011. RESULTS: From 1163 medical students, the mean values of body mass index,
      circumferences of waist, hip, neck, mid-arm, thigh and calf were 20.89 +/-1.6
      kg/m(2), 73.15 +/-5.1 cm, 95.35 +/-4.8 cm, 30.32 +/-1.37 cm, 24.12 +/-1.75 cm,
      47.23 +/-3.26 cm and 34.36 +/-2.19 cm respectively in women, while the same
      measurements were 21.98 +/-1.67 kg/m(2), 77.73 +/-5.81 cm, 95.64 +/-4.81 cm,
      35.61 +/-1.43 cm, 25.60 +/-1.84 cm, 44.10 +/-3.26 cm and 34.92 +/-2.08 cm
      respectively in men. Moreover, waist to hip ratio, waist to height ratio and neck
      to height ratio were respectively 0.76, 0.44 and 0.18 in women and 0.81, 0.43 and
      0.19 in men. CONCLUSIONS: The precise knowledge of anthropometric data could be
      used as reference values for evaluating the body composition and fat distribution
      of Turkish young people.

PMID- 22661992
TI  - Circulating visfatin level and visfatin/insulin ratio in obese women with
      metabolic syndrome.
AB  - INTRODUCTION: Visfatin is an adipokine secreted by visceral adipose tissue with
      insulin-mimetic properties. Higher circulating visfatin levels were reported in
      type 2 diabetes. The aim of this study was to analyse circulating visfatin and
      insulin levels and the visfatin/insulin ratio in obese women with and without
      metabolic syndrome (MetS). MATERIAL AND METHODS: The study involved 92 obese
      women. Subjects were diagnosed with MetS according to IDF 2005 criteria. The MetS
      group consisted of 71 subjects (age: 52.8 +/-9.4 years, body mass index [BMI]:
      39.1 +/-5.6 kg/m(2), waist circumference: 109.6 +/-11.4 cm and fat mass: 52.0 +/
      12.8 kg) while the non-MetS group consisted of 21 subjects (age: 51.7 +/-9.5
      years, BMI: 36.3 +/-5.2 kg/m(2), waist circumference: 104.7 +/-11.0 cm and fat
      mass: 45.2 +/-10.7 kg). In addition to anthropometric measurements and assessment
      of serum glucose and lipids, plasma concentrations of visfatin were estimated by
      enzyme-linked immunosorbent assay (ELISA) and of insulin by radioimmunoassay
      (RIA). Homeostatic model assessment insulin resistance (HOMA-IR) and
      visfatin/insulin ratio were calculated. RESULTS: In the MetS group significantly
      higher (p < 0.01) plasma concentrations of insulin and HOMA-IR values but similar
      visfatin levels were observed than in the non-MetS group. As a consequence of the
      significantly higher plasma insulin concentration the visfatin/insulin ratio was
      significantly lower in the MetS group (p < 0.05). The visfatin/insulin ratio
      correlated inversely with anthropometric parameters such as body mass, BMI, body
      fat and waist circumference (r = -0.41, p = 0.0003; r = -0.42, p = 0.0002; r = 
      0.29, p = 0.01; r = -0.23, p = 0.04, respectively). CONCLUSIONS: We conclude that
      the visfatin/insulin ratio declining with increasing visceral obesity may
      predispose to the development of insulin resistance.

PMID- 22661993
TI  - The association of an adenine insertion variant in the 5'UTR of the endothelin-1
      gene with hypertension and orthostatic hypotension.
AB  - INTRODUCTION: An adenine insertion polymorphism in the 5' untranslated region of
      the endothelin-1 gene is functional and increases the expression of endothelin
      mRNA and protein in the insertion homozygote. In the present study we
      hypothesized that this functional polymorphism might be associated with
      hypertension and/or orthostatic hypotension. MATERIAL AND METHODS: The adenine
      insertion polymorphism was genotyped in 381 untreated hypertensive patients and
      298 normotensive subjects, all of whom underwent an upright posture study for
      orthostatic blood pressure measurements. Orthostatic hypotension was defined as a
      drop in blood pressure of 20/10 mm Hg or more within 3 min of assuming the
      upright posture. RESULTS: The allele frequency of the adenine insertion was
      similar in hypertensive and normotensive subjects (15.2% vs. 15.3%, p > 0.05).
      After adjustment for age, sex and body mass index, blood pressure levels did not
      differ significantly among the genotypes in both hypertensives and normotensives.
      No associations were found between the distribution of the adenine insertion
      genotypes and the risk of orthostatic hypotension in both hypertensive patients
      and normotensive subjects even after adjustment for demographic parameters and
      supine systolic or diastolic blood pressure. Neither hypertensive nor
      normotensive subjects showed significant differences in orthostatic systolic or
      diastolic blood pressure changes among the genotype groups (all p > 0.05).
      CONCLUSIONS: We concluded that the functional adenine insertion polymorphism in
      the endothelin-1 gene is not associated with either hypertension or orthostatic
      hypotension risk in Chinese.

PMID- 22661994
TI  - Cardiac complications associated with trastuzumab in the setting of adjuvant
      chemotherapy for breast cancer overexpressing human epidermal growth factor
      receptor type 2 - a prospective study.
AB  - INTRODUCTION: Trastuzumab, a recombinant humanized monoclonal antibody, is
      targeted against the external domain of the human epidermal growth factor
      receptor type 2 (HER2). It improves efficacy of HER2-positive breast cancer
      treatment. The authors present their experience with patients (pts) treated with
      trastuzumab in the aspects of cardiac complications. MATERIAL AND METHODS: We
      observed prospectively 253 women with early positive HER2 breast cancer treated
      with trastuzumab. Assessment of cardiovascular status, ECG and echocardiography
      was performed initially and every 3 months until 6(th) month during follow-up.
      RESULTS: Cardiac complications developed in 52 pts (20.55%) and included:
      asymptomatic left ventricle dysfunction (43), symptomatic heart failure (6), new
      asymptomatic LBBB (1); new negative T-waves in ECG (2). There was a progressive
      decline in left ventricular ejection fraction (LVEF) during treatment. It was
      more enhanced in pts with cardiac complications. Following trastuzumab
      termination/discontinuation LVEF increased but at month 18 still remained
      significantly lower than initially in both groups (61.07 +/-4.84 vs. 59.97 +/
      5.23 - no cardiac complications; p < 0.05; 58.14 +/-4.08% vs. 53.08 +/-5.74% -
      cardiac complications; p < 0.05). During 6-month follow-up 33 out of 46 pts
      experienced an improvement in left ventricular status. In 13 pts in whom
      trastuzumab was discontinued, it was restarted; 6 of them successfully completed
      total therapy. Univariate analysis revealed no association between any
      cardiovascular risk factor and the development of cardiotoxicity. CONCLUSIONS:
      One out of five treated patients discontinues trastuzumab in an adjuvant setting
      due to cardiac complications. LV dysfunction is the most frequent. Routine
      cardiac monitoring should be obligatory.

PMID- 22661995
TI  - Interaction of cerebrovascular disease and contralateral carotid occlusion in
      prediction of shunt insertion during carotid endarterectomy.
AB  - INTRODUCTION: To assess the possible role and the interaction of cerebrovascular
      disease and vascular stenosis on the necessity of shunt insertion during carotid
      endarterectomy (CEA). MATERIAL AND METHODS: Eighty consecutive patients
      undergoing CEA under regional anaesthesia were prospectively enrolled. Patients
      were divided into two groups depending on whether they were shunted or not. The
      measured end-points were co-morbidities degree of contralateral and carotid
      stenosis and other intra- and postoperative outstanding parameters. ANOVA,
      Student's t and chi(2) tests were used (p<0.05). Variables differing
      significantly between groups and potential confounders were used in backward
      stepwise logistic regression to estimate the relative risk (RR, 95% CI) of shunt.
      In addition Wald's test (p<0.05) with and without adjustments for potential
      confounders was used with various different multivariate analysis models.
      RESULTS: Contralateral stenosis and cerebral vascular accidents (CVA) were more
      frequently observed in shunted patients. The RR for patients with contralateral
      stenosis >= 50% was 1.3 (95% CI 1.0-1.5) and for patients with previous CVA was
      1.2 (95% CI 1.0-1.4). For contralateral stenosis and CVA together the RR
      increased to 7.7 (95% CI 1.0-14.4). A model based on contralateral stenosis and
      CVA was found to be statistically significant (p=0.003) for shunt (RR=1.1, 95% CI
      1.0-2.1). Relative excess risk due to interaction of both factors was 6.2.
      CONCLUSIONS: The findings suggest that patients with contralateral stenosis >=
      50% and previous CVA have a higher risk of requiring shunt use during CEA than
      patients with these risk factors separately.

PMID- 22661996
TI  - Comparison of the clinical application of reactive oxygen species and
      inflammatory markers in patients with endocarditis.
AB  - INTRODUCTION: Infective endocarditis (IE) is still connected with high operative
      mortality. Inflammatory markers are commonly used in monitoring patient clinical
      condition. Respiratory burst and reactive oxygen species (ROS) are the main way
      of pathogen elimination. Specificity of this process in the aspect of bacterial
      infection is the key for correlation assessment between ROS and inflammatory
      markers in patients with IE. In the study, assessment of ROS as a clinical
      indicator in IE was conducted. MATERIAL AND METHODS: During 2007/2008 in the
      Cardiosurgical Clinic of the Medical University in Lodz there were 20 patients
      operated on for IE. The examined population consisted of 13 men and 7 women, aged
      from 23 to 74 years. Inflammatory markers - leukocytosis (WBC), C-reactive
      protein (CRP), procalcitonin (PCT) and erythrocyte sedimentation rate (ESR) -
      were assessed preoperatively, on the 3(rd), 7(th), 12(th) and 21(st) day.
      Simultaneously, with the second venous blood sample chemiluminescence (luminal
      enhanced whole blood chemiluminescence) was carried out and used to assess ROS
      production. The results were analyzed statistically. RESULTS: Positive
      correlation between ESR, CRP and ROS in the preoperative period was confirmed. An
      increase in ROS and a statistically significant increase in inflammatory markers
      on the 3(rd) day were observed. The ROS normalized on the 12(th) day. Marked
      individual variability was specific for the inflammatory markers. Despite the
      significant decrease, not all of them achieved a normal level at the last control
      point. CONCLUSIONS: Assessment of ROS seems to be a universal parameter with
      possible application in patients with IE.

PMID- 22661997
TI  - Plasma neutrophil gelatinase-associated lipocalin as an early biomarker for
      prediction of acute kidney injury after cardio-pulmonary bypass in pediatric
      cardiac surgery.
AB  - INTRODUCTION: Cardiopulmonary bypass (CPB) surgery is considered one of the most
      frequent surgical procedures in which acute kidney injury (AKI) represents a
      frequent and serious complication. The aim of the present study was to evaluate
      the efficiency of neutrophil gelatinase-associated lipocalin (NGAL) as an early
      AKI biomarker after CPB in pediatric cardiac surgery. MATERIAL AND METHODS: The
      study included forty children aged 2 to 78 months undergoing CPB. They were
      divided into group I: patients who suffered AKI grades II and III; and group II:
      patients who did not develop AKI or at risk. Peripheral venous blood was
      withdrawn pre- and post-operatively for serial measurements of NGAL and
      creatinine. Statistical analysis was performed using Statistical Package for
      Social Sciences version 14. RESULTS: Mean plasma NGAL levels showed highly
      significant elevations in group I patients at 2, 12, and 24 h after surgery (p <
      0.0001) compared to group II. Significant correlations were found between NGAL
      and creatinine at different time intervals. Highly significant correlations (p <
      0.0001) were found between plasma NGAL and AKI at 2, 12 and 24 h after surgery. A
      cut-off level of 100 ng/ml at 2 h, and 125 ng/ml at 12 h post-operatively both
      recorded the highest accuracy, being 95% accurate, with sensitivity of 100% and
      89.5% respectively, and specificity of 90.5% and 100% respectively. CONCLUSIONS:
      This study showed that plasma NGAL could be used as an early biomarker for
      detection of AKI following CPB. We recommend further studies on a wider scale to
      validate the current study results.

PMID- 22661998
TI  - Effect of clinical condition and mycophenolate mofetil on plasma retinol, alpha
      tocopherol and beta-carotene in renal transplant recipients.
AB  - INTRODUCTION: Plasma antioxidant vitamins (retinol, alpha-tocopherol, beta
      carotene) were measured to establish the influence of clinical condition and
      mycophenolate mofetil (MMF) treatment on the nutritional status of renal
      transplant recipients. MATERIAL AND METHODS: In 106 adult patients plasma
      vitamins were measured and 24-h diet history questionnaires were conducted. The
      MMF influence on plasma vitamins was verified in 61 patients. RESULTS: The
      current dietary intakes of vitamins in daily food rations were lower than
      recommended. Plasma retinol was lower in patients suffering from gastrointestinal
      disorders (1.25 +/-0.48 mg/l vs. 1.55 +/-0.70 mg/l) and inversely associated with
      aminotransferases activity (p = 0.019) and creatinine clearance (p = 0.021).
      Retinol concentrations were positively associated with plasma creatinine (p =
      0.027) and pharmacokinetic parameters of MMF phenyl glucuronide. beta-Carotene
      concentrations were higher in women (0.39 +/-0.46 mg/l vs. 0.28 +/-0.23 mg/l; p =
      0.041) and when MMF was co-administered with cyclosporine vs. tacrolimus (0.45 +/
      0.62 mg/l vs. 0.25 +/-0.19 mg/l). Plasma alpha-tocopherol correlated negatively
      with the mycophenolic acid pre-dose concentration (p = 0.027) and was
      significantly lower in patients treated with calcineurin inhibitors (8.90 +/-5.23
      mg/l vs. 12.25 +/-5.62 mg/l). A positive correlation was observed between alpha
      tocopherol levels and aspartate aminotransferase (p = 0.006). In multivariate
      regression aspartate aminotransferase and MMF treatment significantly influenced
      retinol (p < 0.001). CONCLUSIONS: The MMF treatment was associated with
      significantly lower retinol concentrations. The gastrointestinal disorders
      occurrence in MMF-treated patients may cause a decrease in retinol absorption.
      Diet adjustment and/or vitamin A supplementation should be considered.

PMID- 22661999
TI  - Hypothyroidism, new nodule formation and increase in nodule size in patients who
      have undergone hemithyroidectomy.
AB  - INTRODUCTION: The current medical literature has conflicting results about
      factors related to hypothyroidism and nodular recurrences during follow-up of
      hemithyroidectomized patients. We aimed to evaluate factors that may have a role
      in new nodule formation, hypothyroidism, increase in thyroid lobe and increase in
      nodule volumes in these patients with and without Hashimoto's thyroiditis (HT),
      and with and without levothyroxine (LT4) use. MATERIAL AND METHODS: We enrolled
      140 patients from five different hospitals in Ankara and evaluated their thyroid
      tests, autoantibody titre results and ultrasonographic findings longitudinally
      between two visits with a minimum 6-month interval. RESULTS: In patients with HT
      there was no significant difference between the two visits but in patients
      without HT, thyroid stimulating hormone (TSH) levels and nodule volume were
      higher, and free T4 levels were lower in the second visit. Similarly, in patients
      with LT4 treatment there was no difference in TSH, free T4 levels, or lobe or
      nodule size between the two visits, but the patients without LT4 had free T4
      levels lower in the second visit. Regression analysis revealed a relationship
      between first visit TSH levels and hypothyroidism during follow-up. CONCLUSIONS:
      Patients who have undergone hemithyroidectomy without LT4 treatment and without
      HT diagnosis should be followed up more carefully for thyroid tests, new nodule
      formation and increase in nodule size. The TSH levels at the beginning of the
      follow-up may be helpful to estimate hypothyroidism in hemithyroidectomized
      patients.

PMID- 22662001
TI  - Exhaled eicosanoids and biomarkers of oxidative stress in exacerbation of chronic
      obstructive pulmonary disease.
AB  - INTRODUCTION: Eicosanoids and oxidants play an important role in inflammation,
      but their role in chronic obstructive pulmonary disease (COPD) is uncertain. In
      this study we hypothesized that levels of exhaled leukotrienes, prostaglandins
      and biomarkers of oxidative stress are increased in infectious exacerbations of
      COPD and that they decrease after antibiotic therapy. MATERIAL AND METHODS:
      Cysteinyl-leukotrienes (LTs), leukotriene B(4) (LTB(4)), prostaglandin E(4),
      hydrogen peroxide (H(2)O(2)) and 8-isoprostane were measured in exhaled breath
      condensate (EBC) in 16 COPD patients with infectious exacerbations (mean age 64
      +/-12 years, 13 male) on day 1, during antibiotic therapy (days 2-4), 2-4 days
      after therapy and at a follow-up visit when stable (21-28 days after therapy).
      RESULTS: There was a significant fall in concentration of cys-LTs, LTB(4) and 8
      isoprostane at visit 3 compared to day 1 (cys-LTs: 196.5 +/-38.4 pg/ml vs. 50.1
      +/-8.2 pg/ml, p < 0.002; LTB(4): 153.6 +/-25.5 pg/ml vs. 71.9 +/-11.3 pg/ml, p <
      0.05; 8-isoprostane: 121.4 +/-14.6 pg/ml vs. 56.1 +/-5.2 pg/ml, p < 0.03,
      respectively). Exhaled H(2)O(2) was higher on day 1 compared to that at visits 2
      and 3 (0.74 +/-0.046 uM vs. 0.52 +/-0.028 uM and 0.35 +/-0.029 uM, p < 0.01 and p
      < 0.01, respectively). Exhaled PGE(2) levels did not change during exacerbations
      of COPD. Exhaled eicosanoids and H(2)O(2) in EBC measured at the follow-up visit
      (stable COPD) were significantly higher compared to those from healthy subjects.
      CONCLUSIONS: We conclude that eicosanoids and oxidants are increased in
      infectious exacerbations of COPD. They are also elevated in the airways of stable
      COPD patients compared to healthy subjects.

PMID- 22662000
TI  - The association of bone mineral density and parathyroid hormone with serum
      magnesium in adult patients with sickle-cell anaemia.
AB  - INTRODUCTION: Bone disorders including osteopenia and osteoporosis are a frequent
      cause of morbidity in sickle-cell disease (SCD). Magnesium (Mg) regulates some
      biological processes important in bone remodelling. We aimed to investigate
      whether serum Mg levels (sMg) may have an impact on bone mineral density (BMD) in
      sickle-cell anaemia (SCA). MATERIAL AND METHODS: Sixty adults with SCA in steady
      state and 20 age- and race-matched healthy blood donors were included in the
      study. The BMD was evaluated with respect to minerals and biochemical indices of
      bone metabolism. Multivariate analysis was performed to determine the factors
      influencing BMD. RESULTS: The mean sMg concentration was 0.64 +/-0.06 (reference
      range 0.7-1.2 mmol/l) for 34% of the population, and 0.86 +/-0.08 mmol/l for 66%.
      There were significant differences between Mg groups and controls in BMD,
      phosphorus (PO(4)), parathyroid hormone (PTH) (p = 0.011, p = 0.011 and p =
      0.0001 respectively) and osteocalcin (OC) (p = 0.030) levels. The sMg was found
      to be associated positively with serum calcium (Ca), PTH and OC (r = 0.585; r =
      0.436; r = 0.351 respectively, all at p < 0.05), and negatively with PO(4) (r = 
      0.312; p < 0.05). Multivariate analysis demonstrated that only PTH (p < 0.05) was
      an independent factor for BMD. Moreover, it identified sMg, OC, and CTX as
      independent factors for PTH (all p < 0.05). CONCLUSIONS: These results indicate
      that serum Mg may be a co-contributing factor in causing low BMD. However, other
      possible aetiologies including decreased PTH and increased bone turnover
      certainly play a role. Based on the present data, it is prudent to monitor sMg
      routinely in this patient population and treat the condition whenever possible.

PMID- 22662002
TI  - Association of TNF-alpha -308G/A, SP-B 1580 C/T, IL-13 -1055 C/T gene
      polymorphisms and latent adenoviral infection with chronic obstructive pulmonary
      disease in an Egyptian population.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of
      disability and death. The most common cause of COPD is smoking. There is evidence
      suggesting that genetic factors influence COPD susceptibility and variants in
      several candidate genes have been significantly associated with COPD. In this
      study, we aimed to investigate the possible association of the TNF-alpha -308,
      SPB+1580, IL-13 -1055 gene polymorphisms and latent adenovirus C infection with
      COPD in an Egyptian population. MATERIAL AND METHODS: Our study included 115
      subjects (75 smokers with COPD, 25 resistant smokers and 15 non-smokers) who were
      subjected to spirometric measurements, identification of adenovirus C and
      genotyping of TNF-alpha -308G/A, SP-B+1580 C/T and IL-13 -1055 C/T polymorphisms
      by real-time PCR. RESULTS: The adenovirus C gene was identified in all subjects.
      The distribution of TNF-alpha genotypes showed no significant differences between
      different groups. However, homozygous A genotype was associated with a
      significant decrease in FEV(1), FEV(1)/FVC and FEF25/75% of predicted in COPD (p
      < 0.05). As regards SP-B genotypes, resistant smokers had a significantly higher
      homozygous T genotype frequency compared to COPD and non smokers (p = 0.005).
      Interleukin 13 genotypes showed no significant difference between different
      groups. There was a significant decrease in FEF25/75% of predicted in T allele
      carriers in COPD patients (p = 0.001). CONCLUSIONS: The COPD is a disease caused
      by the interaction of combined genes and environmental influences, in the
      presence of smoking and latent adenovirus C infection, TNF-alpha -308A, SPB +1580
      T and IL-13 -1055 T polymorphisms predispose to the development of COPD.

PMID- 22662003
TI  - Effects of peripheral neuropathy on exercise capacity and quality of life in
      patients with chronic obstructive pulmonary diseases.
AB  - INTRODUCTION: Chronic obstructive pulmonary diseases (COPD) have some systemic
      effects including systemic inflammation, nutritional abnormalities, skeletal
      muscle dysfunction, and cardiovascular, skeletal and neurological disorders. Some
      studies have reported the presence of peripheral neuropathy (PNP) at an incidence
      of 28-94% in patients with COPD. Our study aimed to identify whether PNP affects
      exercise performance and quality of life in COPD patients. MATERIAL AND METHODS:
      Thirty mild-very severe patients with COPD (male/female = 29/1, mean age = 64 +/
      10 years) and 14 normal subjects (male/female = 11/5, mean age = 61 +/-8 years)
      were included in the present study. All subjects underwent pulmonary function
      testing (PFT), cardiopulmonary exercise testing, electroneuromyography and short
      form 36 (SF-36). RESULTS: Peak oxygen uptake (PeakVO(2)) was lower in COPD
      patients (1.15 +/-0.53 l/min) than healthy subjects (2.02 +/-0.46 l/min) (p =
      0.0001). There was no PNP in healthy subjects while 16 (53%) of the COPD patients
      had PNP. Forced expiratory volume in 1 s (FEV(1)) and PeakVO(2) were
      significantly different between patients with PNP and those without (p = 0.009, p
      = 0.03 respectively). Quality of life of patients with PNP was lower than that of
      patients without PNP (p < 0.05). CONCLUSIONS: The present study demonstrates the
      exercise limitation in COPD patients with PNP. Thus, presence of PNP has a poor
      effect on exercise capacity and quality of life in patients with COPD.
      Furthermore, treatment modalities for PNP can be recommended to these patients in
      order to improve exercise capacity and quality of life.

PMID- 22662004
TI  - A case-control study on risk factors of breast cancer in China.
AB  - INTRODUCTION: To screen the risk factors associated with breast cancer among
      Chinese women in order to evaluate the individual risk of developing breast
      cancer among women in China. MATERIAL AND METHODS: A case-control study on 416
      breast cancer patients and 1156 matched controls was conducted in 14 hospitals in
      8 provinces of China in 2008. Controls were age- and region-matched to the cases.
      Clinicians conducted in-person interviews with the subjects to collect
      information on demographics and suspected risk factors for breast cancer that are
      known worldwide. Conditional logistic regression was used to derive odds ratios
      (OR) and 95% confidence intervals (CI) for the associations between risk factors
      and breast cancer. RESULTS: Compared with matched controls, women with breast
      cancer were significantly more likely to have higher body mass index (BMI, OR =
      4.07, 95% CI: 2.98-5.55), history of benign breast disease (BBD) biopsy (OR =
      1.68, 95% CI: 1.19-2.38), older age of menarche (AOM) (OR = 1.41, 95% CI: 1.07
      1.87), stress anticipation (SA), for grade 1-4, OR = 2.15, 95% CI: 1.26-3.66; for
      grade 5-9, OR = 3.48, 95% CI: 2.03-5.95) and menopause (OR = 2.22, 95% CI: 1.50
      3.282) at the level of p < 0.05. Family history of breast cancer (FHBC) in first
      degree relatives (OR = 1.66, 95% CI: 0.77-3.59) and use of oral contraceptives
      (OC) (OR = 1.59, 95% CI: 0.83-3.05) were associated with an increased risk of
      breast cancer at the level of p < 0.20. CONCLUSIONS: Our results showed that BMI,
      history of BBD biopsy, older AOM, SA and menopause were associated with increased
      risk of breast cancer among Chinese women. The findings derived from the study
      provided some suggestions for population-based prevention and control of breast
      cancer in China.

PMID- 22662005
TI  - Pathological complete response in younger and older breast cancer patients.
AB  - INTRODUCTION: Pathologic complete response (pCR) after neoadjuvant systemic
      treatment for inoperable locally advanced breast cancer is defined as complete
      microscopic disappearance of invasive cancer in both the breast and axilla in the
      postoperative specimen. The aim of the study was to characterize the groups of
      younger (<= 40 years old) and older (>= 70 years old) breast cancer patients who
      achieved a pCR. MATERIAL AND METHODS: One hundred thirty-eight consecutive
      patients aged between 30 and 78 years with locally advanced breast cancer,
      operated on after neoadjuvant systemic treatment between November 2007 and June
      2010, were analyzed. In this group 9 women (6.5%) were 40 years of age or
      younger, and 12 patients (8.7%) were 70 years of age or older. RESULTS: In the
      younger group, pCR was achieved in 1 patient with triple negative, invasive
      ductal breast cancer, G3, BRCA 1 mutation, treated with cisplatin. A near pCR was
      achieved in 2 other patients, with triple negative, invasive ductal breast
      cancer, G3, treated with AT. The pCR in the breast was found in a HER2 positive
      patient. In older patients, pCR was achieved in 2 patients with triple negative,
      invasive ductal breast cancer, G3, treated with AT or FEC. Pathologic complete
      response in the axilla was achieved in 1 patient with triple negative, ductal
      carcinoma. The pCR rates were significantly higher in triple negative breast
      cancer in both groups (p = 0.047 and p = 0.018, respectively). CONCLUSIONS:
      Pathologic complete response was significantly associated with receptor- based
      subtypes in both young and old women.

PMID- 22662006
TI  - Primary oral and maxillofacial liposarcoma: a clinicopathological and
      immunohistochemical study of eleven cases.
AB  - INTRODUCTION: The present study was aimed to characterize the
      clinicopathological, immunohistochemical features and treatment outcomes of
      primary oral and maxillofacial liposarcomas by presenting the experience over a
      16-year period at a tertiary referral Chinese institution for head neck cancer.
      MATERIAL AND METHODS: This retrospective clinical study included 11 cases of
      pathologically confirmed primary liposarcomas treated from January 1993 to
      September 2009. Detailed information regarding primary site, clinical
      manifestations, histopathological and immunohistochemical analysis, treatments
      and prognosis was collected and reported. RESULTS: Eight female and 3 male
      patients aged from 8 to 76 years old. These lesions occurred in buccal (3),
      parotid (2), temporal (2), tongue (2), palate (1) and oropharyngeal (1) region.
      They were histopathologically categorized into 4 subtypes based on WHO
      classification scheme: atypical lipomatous tumor/well-differentiated (4), myxoid
      (4), mixed-type (2) and pleomorphic (1) liposarcomas. Immunohistochemical
      staining indicated mostly positive for Vimentin and S-100 but negative for other
      markers. Most patients presented as slow-growing painless masses and underwent
      surgery alone or combined with postoperative radiotherapy. Two patients were
      misdiagnosed and inappropriate treated and developed local relapse before
      referred to our institute. No distant metastasis and one disease-related death
      were recorded during the follow-up (ranging: 1-11 years, mean: 4.5 years).
      CONCLUSIONS: Oral and maxillofacial liposarcoma is exceedingly rare and has
      atypical clinical manifestations but characteristic histopathology. Complete
      excision with negative margins followed by long-term follow-up is recommended as
      the treatment of choice for these uncommon entities.

PMID- 22662007
TI  - Low serum IgA and increased expression of CD23 on B lymphocytes in peripheral
      blood in children with regressive autism aged 3-6 years old.
AB  - INTRODUCTION: Immune system dysfunction is considered to be one of many medical
      disorders found in children with autism. The primary objective of the study was
      to assess if blood tests reflecting humoral immunity (IgA, IgG, IgM, IgE) are
      useful in identifying children with regressive autism. The secondary objective
      was to evaluate a part of the cellular arm of immunity (CD4/CD25 Tregs, CD4/CD23
      cells) in those children. MATERIAL AND METHODS: Using a clinical case-control
      design, the systemic levels of immunoglobulins and lymphocyte subpopulations
      analysed by flow cytometry were compared in children aged 3-6 years old with a
      new diagnosis of regressive autism (n = 24; mean age: 4.25 +/-1.70 years; male
      23/24) and in sex- and age-matched healthy children (n = 24; aged 4.25 +/-2.20
      years; male 23/24). RESULTS: The humoral immunity profile, described by three
      binary variables, IgA < 0.97 g/l, IgE > 36 IU/ml, and IgG > 6.3 g/l, with a
      sensitivity of 79% and a specificity of 83% (p < 0.0001), was able to identify
      children with autism. The highest risk of autism diagnosis was associated with
      IgA < 0.97g/l (OR - 23.0; p < 0.001). A higher number of CD19/CD23 was found in
      children diagnosed with autism than in the control group (36.82 +/-6.72% vs.
      18.20 +/-3.95%; p < 0.02). No correlation between the number of CD23-positive
      cells and serum IgE levels was observed. CONCLUSIONS: A subtle shift of serum
      immunoglobulins consisting of low-normal IgA and B cell activation expressed by
      an increase of CD23-positive cells may characterize children with regressive
      autism aged 3-6 years old.

PMID- 22662008
TI  - Multifactorial analysis of risk factors for reduced bone mineral density among
      postmenopausal women.
AB  - INTRODUCTION: The study aimed to determine the risk factors for reduced bone
      mineral density (BMD) among postmenopausal women. MATERIAL AND METHODS: Two
      hundred and fifty-three postmenopausal women were included to the study. The
      study group consisted of 85 women with osteoporosis (mean age: 59.9 years) and
      168 with osteopenia (mean age: 57.8 years). Patients were assigned to groups
      according to their BMD measured in the lumbar spine, hip and femoral neck by dual
      X-ray absorptiometry. Bone formation was assessed by measuring serum osteocalcin
      and bone resorption by measuring serum C-terminal type I alpha-collagen chain
      telopeptide. RESULTS: Multiple regression analysis for lumbar spine showed
      association of age (p = 0.001), parental history of fracture (p = 0.05), use of
      hormone replacement therapy (p = 0.034), bisphosphonates therapy (p < 0.001),
      calcium and vitamin D supplements therapy (p = 0.001), oestradiol level (p =
      0.007) and body mass index (p < 0.001). Multiple regression analysis for femoral
      neck and hip total showed association of age (p = 0.001), parental history of
      fracture (p = 0.049), use of bisphosphonates (p < 0.03)) use of calcium and
      vitamin D supplements (p = 0.039), oestradiol level (p = 0.047). All the
      variables together explain 40.4% of variance in BMD for the lumbar spine and
      25.6% of variance in BMD for femoral neck and hip total. CONCLUSIONS: The present
      study demonstrated correlations between the variables and BMD, which are known
      and widely described in the literature. Osteoporosis and osteopenia in Polish
      subjects appear to be associated with several known risk factors that are well
      described in the literature.

PMID- 22662009
TI  - Insulin resistance in women with hirsutism.
AB  - INTRODUCTION: There are still not enough data showing whether patients with
      idiopathic hirsutism (IH) also have insulin resistance. The association between
      polycystic ovary syndrome (PCOS) and insulin resistance is well documented in the
      literature, but the Rotterdam Consensus has concluded that principally obese
      women with PCOS should be screened for the metabolic syndrome. We intended to
      investigate the presence/absence of insulin resistance in non-obese women with
      hirsutism. MATERIAL AND METHODS: Twenty-eight women with PCOS (14 non-obese and
      14 obese), 12 non-obese with IH, and 16 non-obese healthy women were included in
      the study. The presence of insulin resistance was investigated by using basal
      insulin levels and the homeostasis model assessment (HOMA) score in the study
      group. RESULTS: Patients with obese and nonobese PCOS had significantly (p <
      0.05) higher basal insulin levels and HOMA scores than IH and control subjects.
      Insulin levels and HOMA scores did not differ between obese and non-obese PCOS
      patients. Patients with IH did not show any difference from the control group.
      CONCLUSIONS: Insulin resistance exists in non-obese women with PCOS as well as
      obese women with PCOS. The PCOS is associated with insulin resistance independent
      of obesity. Insulin resistance should be assessed in all hirsute women with PCOS
      regardless of their body mass index. More studies in larger numbers of patients
      should be performed to investigate the role of insulin resistance in women with
      IH.

PMID- 22662010
TI  - Pathogenic activity of circulating anti-desmoglein-3 autoantibodies isolated from
      pemphigus vulgaris patients.
AB  - INTRODUCTION: There are scarce data on immunochemical properties of pemphigus
      antibodies detected in clinical remission in pemphigus vulgaris (PV) patients.
      The aim of the study was to compare biological activity of anti-Dsg3
      autoantibodies purified from the sera of PV patients in active stage and in
      clinical remission. MATERIAL AND METHODS: The effect of purified antibodies on
      expression of procaspase-3, Bax, Bcl-2, uPAR, IL-1beta, IL-6, and TNF-alpha mRNAs
      in the HaCaT keratinocytes was evaluated by Western blot and RT-PCR method.
      RESULTS: Incubation of HaCaT cells with anti-Dsg-3 autoantibodies caused their
      binding to cell membranes surfaces. Anti-Dsg3 autoantibodies isolated from the
      patients in active stage and clinical remission showed proapoptotic effect,
      caused enhanced expression of analyzed proinflammatory cytokines' mRNAs and uPAR
      mRNA. CONCLUSIONS: Our data revealed similar pathogenic activity of anti Dsg-3
      autoantibodies isolated from active and clinical remission PV patients.

PMID- 22662011
TI  - GABA-A receptor genes do not play a role in genetics of Lesch's typology in
      Caucasian subjects.
AB  - INTRODUCTION: Lesch's typology differentiates alcoholics into different treatment
      response subgroups. The effects of ethanol are mediated, to an important extent,
      via the GABA-ergic system. MATERIAL AND METHODS: We have evaluated the linkage
      disequilibrium patterns and haplotype frequencies of GABRG1 and GABRA2 genes in
      133 alcoholics divided according to Lesch's typology and in 145 matched controls.
      RESULTS: Besides several relationships at a threshold of statistical
      significance, we found no significant differences in the haplotype distribution
      of these genes between alcoholics and controls. CONCLUSIONS: Lesch's typology may
      not be related with the genotype of alcoholics - at least in terms of genes with
      an established role in the development of dependency.

PMID- 22662012
TI  - Amphetamine use and its associated factors in body builders: a study from Tehran,
      Iran.
AB  - INTRODUCTION: Epidemiological studies on all types of illicit drug use among
      athletes are essential for both the sport community and drug control
      achievements. Here, we investigated the prevalence and associated factors of
      amphetamine use in body builders in Tehran, Iran, 2007. MATERIAL AND METHODS:
      This study is a secondary analysis of a substance use survey done in 103 randomly
      selected gymnasia in Tehran (capital city of Iran). The survey was conducted from
      November 2007 to January 2008 and included 843 randomly selected bodybuilders
      (aged 40 years or less). By interviews via questionnaires the following data were
      obtained: age, job, marital status, education level, housing status, average
      monthly family income, number of family members, gymnasium area (m(2)), number of
      trainers, number of gymnasium members, initiation time (months), weekly duration
      of the sporting activity (h), monthly cost of the sporting activity, purpose of
      participating in sporting activity, and history of anabolic steroid and
      amphetamine use. RESULTS: One hundred twenty (13.3%) body builders reported a
      history of amphetamine use. According to the results of regression analysis,
      being married (risk ratio - RR = 0.540), and participating in body building to
      enhance self-esteem (RR = 0.423) or to enhance sport performance (RR = 0.545) had
      protective effects on amphetamine use. However, having university qualifications
      (RR = 1.843), using anabolic steroids (RR = 1.803) and participating in sport to
      maintain fitness (RR = 2.472) were linked to increased risk of amphetamine use.
      CONCLUSIONS: Well-educated bodybuilders were more likely to use amphetamines, and
      why this is so needs to be discovered. If further studies show that they are not
      aware of the dangers associated with amphetamine use, providing them with
      information should be considered.

PMID- 22662013
TI  - Do weekend oocyte retrievals have an impact on the intracytoplasmic sperm
      injection cycles outcome?
AB  - INTRODUCTION: Despite the fact that ovarian stimulation is controlled, it is not
      always predictable. Because the day of human chorionic gonadotrophin (hCG)
      injection depends mainly on the patient's ovarian response to gonadotrophins, the
      day of oocyte retrieval cannot be determined in advance. As a result, oocyte
      retrievals are often scheduled to occur on weekends, a fact that entails at least
      one extra working day for the staff, and could lead to physical and psychological
      stress, especially in embryologists. The aim of this study was to evaluate
      whether intracytoplasmic sperm injection (ICSI) outcomes are influenced by the
      day of oocyte retrieval. MATERIAL AND METHODS: A total of 327 ICSI cycles, whose
      retrievals were performed on Wednesdays and Sundays, were analysed in this
      retrospective study. Cycles were subdivided into two groups according to the day
      of oocyte retrieval: group W (n = 196), cycles in which oocyte retrieval was
      performed on Wednesday; and group S (n = 131), cycles in which oocyte retrieval
      was performed on Sunday. Groups were compared regarding fertilization,
      implantation, pregnancy and take-home baby rates. RESULTS: No significant
      differences were observed between groups A and B regarding fertilization rate
      (68.9% and 72.5%; p = 0.1589), implantation rate (21.8% and 24.3%; p = 0.5714),
      pregnancy rate (29.9% and 31.6%; p = 0.7129) and take-home baby rate (23.6% and
      28.1%; p = 0.4351). CONCLUSIONS: A well-trained embryologist's group adhering to
      staff scheduling allows large programmes to ensure a similar outcome independent
      of the workload or workday on which embryologists perform the manipulation of
      gametes.

PMID- 22662014
TI  - Hemodynamic findings in patients with brain stroke.
AB  - INTRODUCTION: Standard procedures carried out at a stroke department in patients
      after a cerebral event may prove insufficient for monitoring hemodynamic indices.
      Impedance cardiography enables hemodynamic changes to be monitored non
      invasively. The aim of the work was to describe hemodynamic parameters in
      patients with acute phase of ischemic and hemorrhagic stroke and to analyse the
      correlation between the type of hemodynamic response and long-term prognosis.
      MATERIAL AND METHODS: The 45 consecutive subjects with ischemic stroke and 16
      with a hemorrhagic stroke were examined additionally with impedance cardiography
      during the first day of hospitalization. The heart contractility, pump
      performance, afterload and preload indices were recorded and calculated
      automatically and the data analyzed in terms of 6-month mortality. RESULTS: We
      found a significant association between the systemic vascular resistance index,
      Heather index, stroke index, heart rate, systolic and diastolic and mean arterial
      blood pressure and mortality in patients with ischemic stroke (p = 0.002, p =
      0.008, p = 0.012, p = 0.005, p = 0.007, p = 0.009, p = 0.002 respectively).
      Logistic regression analysis identified the thoracic fluid content as the most
      significant variable correlating with the non-survival of the patients with
      ischemic stroke and in the whole group (ischemic and hemorrhagic stroke). The
      significant parameters were also mean arterial pressure and stroke index in
      ischemic stroke (the correct answer ratio was 86.67%) and heart rate in the whole
      group (the correct answer ratio was 80.33%). There were no significant
      associations in hemorrhagic stroke. CONCLUSIONS: The hemodynamic parameters
      correlate with long term prognosis in patients with ischemic brain stroke.

PMID- 22662016
TI  - Hepatocyte growth factor concentration during the first day of acute coronary
      syndrome.

PMID- 22662017
TI  - Extra-gastrointestinal stromal tumor of the liver diagnosed by ultrasound-guided
      fine needle aspiration cytology: a case report and review of the literature.

PMID- 22662015
TI  - Peripheral arterial disease of the lower extremities.
AB  - Persons with peripheral arterial disease (PAD) are at increased risk for all
      cause mortality, cardiovascular mortality, and mortality from coronary artery
      disease. Smoking should be stopped and hypertension, dyslipidemia, diabetes
      mellitus, and hypothyroidism treated. Statins reduce the incidence of
      intermittent claudication and improve exercise duration until the onset of
      intermittent claudication in persons with PAD and hypercholesterolemia. The serum
      low-density lipoprotein cholesterol should be reduced to < 70 mg/dl. Antiplatelet
      drugs such as aspirin or clopidogrel, angiotensin-converting enzyme inhibitors,
      and statins should be given to persons with PAD. beta-Blockers should be given if
      coronary artery disease is present. Cilostazol improves exercise time until
      intermittent claudication. Exercise rehabilitation programs should be used.
      Revascularization should be performed if indicated.

PMID- 22662018
TI  - Platelet storage and transfusions: new concerns associated with an old therapy.
AB  - Platelet transfusion has long been practiced with rudimentary knowledge about
      optimal storage conditions and their implications for efficacy and, particularly,
      safety. Recent concerns about complications such as inflammation, thrombosis and
      altered recipient immunity have been raised about platelet transfusion. This
      review will discuss recent important findings that have raised these issues about
      platelet transfusion associated morbidity, mortality and the possible role of
      platelet storage in these associations.

PMID- 22662019
TI  - Taxonomy and Chemotaxonomy of the Genus Hypericum.
AB  - The genus Hypericum L. (St. John's Wort, Hypericaceae) includes, at the most
      recent count, 469 species that are either naturally occurring on, or which have
      been introduced to, every continent in the world, except Antarctica. These
      species occur as herbs, shrubs, and infrequently trees, and are found in a
      variety of habitats in temperate regions and in high mountains in the tropics,
      avoiding only zones of extreme aridity, temperature and/or salinity. Monographic
      work on the genus has resulted in the recognition and description of 36 taxonomic
      sections, delineated by specific combinations of morphological characteristics
      and biogeographic distribution ranges. Hypericum perforatum L. (Common St. John's
      wort, section Hypericum), one of the best-known members of the genus, is an
      important medicinal herb of which extracts are taken for their reported activity
      against mild to moderate depression. Many other species have been incorporated in
      traditional medicine systems in countries around the world, or are sold as
      ornamentals. Several classes of interesting bioactive secondary metabolites,
      including naphthodianthrones (e.g. hypericin and pseudohypericin), flavonol
      glycosides (e.g. isoquercitrin and hyperoside), biflavonoids (e.g.
      amentoflavone), phloroglucinol derivatives (e.g. hyperforin and adhyperforin) and
      xanthones have been identified from members of the genus. A general overview of
      the taxonomy of the genus and the distribution of relevant secondary metabolites
      is presented.

PMID- 22662021
TI  - Nano-technology and nano-toxicology.
AB  - Rapid developments in nano-technology are likely to confer significant benefits
      on mankind. But, as with perhaps all new technologies, these benefits are likely
      to be accompanied by risks, perhaps by new risks. Nano-toxicology is developing
      in parallel with nano-technology and seeks to define the hazards and risks
      associated with nano-materials: only when risks have been identified they can be
      controlled. This article discusses the reasons for concern about the potential
      effects on health of exposure to nano-materials and relates these to the evidence
      of the effects on health of the ambient aerosol. A number of hypotheses are
      proposed and the dangers of adopting unsubstantiated hypotheses are stressed.
      Nano-toxicology presents many challenges and will need substantial financial
      support if it is to develop at a rate sufficient to cope with developments in
      nano-technology.

PMID- 22662022
TI  - Conducting Community Research in Rural China -Addressing the Methodological
      Challenges of Recruiting Participants in Rapidly Changing Social Environments.
AB  - BACKGROUND: The paper addressed a unique challenge for public health and
      community research in rural China, i.e., the very large percentage of young
      adults that comprises a highly mobile working population that has been an
      essential component of the country's economic transformation. Fluid local
      demographic patterns potentially have a substantial impact on sample
      representativeness and data validity.  METHODS: This report is based upon a cross
      sectional survey with face-to-face interviews of residents aged 16-34 years in
      rural communities of Mianyang, Sichuan Province, China. Two waves of fieldwork
      and other strategies were adopted in response to recruitment challenges. 
      RESULTS: 1654 of 3008 potential participants took part in the study; this
      constituted 98% of those individuals approached and 55% of the persons enumerated
      in the local household registration system (hukou). Analyses revealed substantial
      differences among those who were interviewed during September and October 2005,
      versus those seen during the Chinese Lunar New Year of 2006 when many migrant
      workers and students returned to their homes. Both groups together differed from
      those who were unavailable during either recruiting episode.  DISCUSSION AND
      CONCLUSIONS: We discuss potential responses to associated methodological
      challenges, including, (1) permanent hukou mismatches; (2) temporary hukou
      mismatches; (3) difficulties faced by potential participants to fully understand
      the purpose of research, the informed consent process, and specific research
      questions; and (4) appreciation of the importance of local social networks, as
      they pertain in particular to rural China. These findings underscore that there
      may be a need to make "on-the-ground" adjustments to varying local conditions to
      maximize sample representativeness and data validity.

PMID- 22662020
TI  - Morphological and Phytochemical Diversity among Hypericum Species of the
      Mediterranean Basin.
AB  - The genus Hypericum L. (St. John's wort, Hypericaceae) includes more than 450
      species that occur in temperature or tropical mountain regions of the world.
      Monographic work on the genus has resulted in the recognition and description of
      36 taxonomic sections, delineated by specific combinations of morphological
      characteristics and biogeographic distribution. The Mediterranean Basin has been
      recognized as a hot spot of diversity for the genus Hypericum, and as such is a
      region in which many endemic species occur. Species belonging to sections
      distributed in this area of the world display considerable morphological and
      phytochemical diversity. Results of a cladistic analysis, based on 89
      morphological characters that were considered phylogenetically informative, are
      given here. In addition, a brief overview of morphological characteristics and
      the distribution of pharmaceutically relevant secondary metabolites for species
      native to this region of the world are presented.

PMID- 22662024
TI  - Role of science and judgment in setting national ambient air quality standards:
      how low is low enough?
AB  - The Clean Air Act (CAA) requires listing as criteria air pollutants those
      pollutants that arise from multiple sources and are found across the United
      States. The original list included carbon monoxide, nitrogen oxides, sulfur
      oxides, particulate matter, photochemical oxidants (later regulated as ozone),
      and hydrocarbons. Later, the listing of hydrocarbons was revoked and lead was
      listed. The CAA requires the EPA Administrator to set National Ambient Air
      Quality Standards (NAAQS) for these pollutants using the "latest scientific
      knowledge" at levels that, in the judgment of the Administrator, are "requisite
      to protect public health" while "allowing an adequate margin of safety" without
      considering the cost of implementing the NAAQS. The NAAQS are set using
      scientific knowledge to inform the Administrator's policy judgments on each
      NAAQS. Recently, there has been increasing tension and debate over the role of
      scientific knowledge versus policy judgment in the setting of NAAQS. This paper
      reviews key elements of this debate drawing on the opinion of Supreme Court
      Justice Stephen Breyer, in Whitman v. American Trucking Associations, to resolve
      the conundrum posed by the CAA language. I conclude that scientists should
      carefully distinguish between their interpretations of scientific knowledge on
      specific pollutants and their personal preferences as to a given policy outcome
      (i.e., specific level and form of the NAAQS), recognizing that these are policy
      judgments as to acceptable levels of risk if the science does not identify a
      threshold level below which there are no identifiable health risks. These policy
      judgments are exclusively delegated by the CAA to the EPA Administrator who needs
      to articulate the basis for their policy judgments on the level and form of the
      NAAQS and associated level of acceptable risk.

PMID- 22662023
TI  - Confounding and exposure measurement error in air pollution epidemiology.
AB  - Studies in air pollution epidemiology may suffer from some specific forms of
      confounding and exposure measurement error. This contribution discusses these,
      mostly in the framework of cohort studies. Evaluation of potential confounding is
      critical in studies of the health effects of air pollution. The association
      between long-term exposure to ambient air pollution and mortality has been
      investigated using cohort studies in which subjects are followed over time with
      respect to their vital status. In such studies, control for individual-level
      confounders such as smoking is important, as is control for area-level
      confounders such as neighborhood socio-economic status. In addition, there may be
      spatial dependencies in the survival data that need to be addressed. These issues
      are illustrated using the American Cancer Society Cancer Prevention II cohort.
      Exposure measurement error is a challenge in epidemiology because inference about
      health effects can be incorrect when the measured or predicted exposure used in
      the analysis is different from the underlying true exposure. Air pollution
      epidemiology rarely if ever uses personal measurements of exposure for reasons of
      cost and feasibility. Exposure measurement error in air pollution epidemiology
      comes in various dominant forms, which are different for time-series and cohort
      studies. The challenges are reviewed and a number of suggested solutions are
      discussed for both study domains.

PMID- 22662025
TI  - Europe's Care Regimes and the Role of Migrant Care Workers Within Them.
AB  - This paper is an examination of the recent restructuring and subsequent
      convergence of European long-term care models. This paper also aims to highlight
      the increased role of migrant care workers and the need for great social and
      governmental recognition for all care providers. The provision of long term care
      is complex, divided between state, market and family providers; the state alone
      could not and does not act as the sole provider of care (Banks 1998). The extent
      to which different sectors are relied upon is largely dependent on the ideology
      of the country's welfare state (Timonen and Doyle 2007).

PMID- 22662026
TI  - Dynamic in situ chromosome immobilisation and DNA extraction using localized
      poly(N-isopropylacrylamide) phase transition.
AB  - A method of in situ chromosome immobilisation and DNA extraction in a
      microfluidic polymer chip was presented. Light-induced local heating was used to
      induce poly(N-isopropylacrylamide) phase transition in order to create a hydrogel
      and embed a single chromosome such that it was immobilised. This was achieved
      with the use of a near-infrared laser focused on an absorption layer integrated
      in the polymer chip in close proximity to the microchannel. It was possible to
      proceed to DNA extraction while holding on the chromosome at an arbitrary
      location by introducing protease K into the microchannel.

PMID- 22662027
TI  - Non-positional cell microarray prepared by shape-coded polymeric microboards: A
      new microarray format for multiplex and high throughput cell-based assays.
AB  - A non-positional (or suspension) cell microarray was developed using shape-coded
      SU-8 photoresist microboards for potential application in multiplex and high
      throughput cell-based assays. A conventional photolithography process on glass
      slides produced various shapes of SU-8 micropatterns that had a lateral dimension
      of 200 MUm and a thickness of 40 MUm. The resultant micropatterns were detached
      from the slides by sonication and named "microboards" due to the fact that had a
      much larger lateral dimension than thickness. The surfaces of the SU-8
      microboards were modified with collagen to promote cell adhesion, and it was
      confirmed that collagen-coated SU-8 microboards supported cell adhesion and
      proliferation. Seeding of cells into poly(ethylene glycol)(PEG) hydrogel-coated
      well plates containing collagen-modified microboards resulted in selective cell
      adhesion onto the microboards due to the non-adhesiveness of PEG hydrogel toward
      cells, thereby creating non-positional arrays of microboards carrying cells.
      Finally, two different cell types (fibroblasts and HeLa cells) were separately
      cultured on different shapes of microboards and subsequently mixed together to
      create a non-positional cell microarray consisting of multiple cell types where
      each cell could be easily identified by the shape of the microboard to which they
      had adhered. Because numerous unique shapes of microboards can be fabricated
      using this method by simply changing the photomask designs, high throughput and
      multiplex cell-based assays would be easily achieved with this system in the
      future.

PMID- 22662028
TI  - A microfluidic chip for highly efficient cell capturing and pairing.
AB  - This paper examined the feasibility of a microfluidics chip for cell capturing
      and pairing with a high efficiency. The chip was fabricated by the
      polydimethylsiloxane-based soft-lithography technique and contained two suction
      duct arrays set in parallel on both sides of a main microchannel. Cells were
      captured and paired by activating two sets of suction ducts one by one with the
      help of syringe pumps along with switching the cell suspensions inside the main
      microchannel correspondingly. The effects of suction flow rate and the dimensions
      of suction channels on the cell capturing and pairing efficiency were
      characterized. The present chip was capable of creating 1024 pairs of two
      different cell populations in parallel. The preliminary experimental results
      showed that the cell capturing efficiency was 100% and the pairing one was 88%
      with an optimal suction rate of 5 MUl/min in the chip in the 2 MUm-sized suction
      duct chip. The cell viability after capture inside the microfluidic device was
      90.0 +/- 5.3%. With this cell capturing and pairing chip, interaction between
      cells in a single pair mode can be studied. The ability to create cell pairs has
      a number of biological applications for cell fusion, cell-cell interaction
      studies, and cell toxicity screening.

PMID- 22662029
TI  - Microfluidic endothelial cell culture model to replicate disturbed flow
      conditions seen in atherosclerosis susceptible regions.
AB  - Atherosclerotic lesions occur non-randomly at vascular niches in bends and
      bifurcations where fluid flow can be characterized as "disturbed" (low shear
      stress with both forward and retrograde flow). Endothelial cells (ECs) at these
      locations experience significantly lower average shear stress without change in
      the levels of pressure or strain, which affects the local balance in mechanical
      stresses. Common in vitro models of atherosclerosis focus primarily on shear
      stress without accounting for pressure and strain loading. To overcome this
      limitation, we used our microfluidic endothelial cell culture model (ECCM) to
      achieve accurate replication of pressure, strain, and shear stress waveforms
      associated with both normal flow seen in straight sections of arteries and
      disturbed flow seen in the abdominal aorta in the infrarenal segment at the wall
      distal to the inferior mesenteric artery (IMA), which is associated with high
      incidence of atherosclerotic lesion formation. Human aortic endothelial cells
      (HAECs) were cultured within the ECCM under both normal and disturbed flow and
      evaluated for cell shape, cytoskeletal alignment, endothelial barrier function,
      and inflammation using immunofluorescence microscopy and flow cytometry. Results
      clearly demonstrate quantifiable differences between cells cultured under
      disturbed flow conditions, which are cuboidal with short and randomly oriented
      actin microfilaments and show intermittent expression of beta-Catenin and cells
      cultured under normal flow. However, in the absence of pro-inflammatory
      stimulation, the levels of expression of activation markers: intra cellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1),
      platelet endothelial cell adhesion molecule-1 (PECAM-1), and vascular endothelial
      cell growth factor - receptor 2 (VEGF-R2) known to be involved in the initiation
      of plaque formation were only slightly higher in HAECs cultured under disturbed
      flow in comparison to cells cultured under normal flow.

PMID- 22662030
TI  - Nanofiber-modified surface directed cell migration and orientation in
      microsystem.
AB  - Cell-microscale pattern surface interactions are crucial to understand many
      fundamental biological questions and develop regenerative medicine and tissue
      engineering approaches. In this work, we demonstrated a simple method to pattern
      PDMS surface by sacrificing poly vinyl pyrrolidone (PVP) electrospinning
      nanofibers and investigated the growth profile of cells on the modified patterned
      surfaces using stroma cells. The stromal cells were observed to exhibit good
      viability on this modified surface and the patterned surface with alignment
      nanofibers could promote cell migration. Furthermore, the modified PDMS surface
      was integrated with microfluidic channels to create the microscale spatial factor
      and was used to explore the cell migration and orientation under this
      microsystem. Both spatial factor and patterned surfaces were found to contribute
      to the complex cell orientation under the combined dual effects. This established
      method is simple, fast, and easy for use, demonstrating the potential of this
      microsystem for applications in addressing biological questions in complex
      environment.

PMID- 22662031
TI  - Optofluidic characterization of marine algae using a microflow cytometer.
AB  - The effects of global warming, pollution in river effluents, and changing ocean
      currents can be studied by characterizing variations in phytoplankton
      populations. We demonstrate the design and fabrication of a Microflow Cytometer
      for characterization of phytoplankton. Guided by chevron-shaped grooves on the
      top and bottom of a microfluidic channel, two symmetric sheath streams wrap
      around a central sample stream and hydrodynamically focus it in the center of the
      channel. The lasers are carefully chosen to provide excitation light close to the
      maximum absorbance wavelengths for the intrinsic fluorophores chlorophyll and
      phycoerythrin, and the excitation light is coupled to the flow cytometer through
      the use of an optical fiber. Fluorescence and light scatter are collected using
      two multimode optical fibers placed at 90-degree angles with respect to the
      excitation fiber. Light emerging from these collection fibers is directed through
      optical bandpass filters into photomultiplier tubes. The cytometer measured the
      optical and side scatter properties of Karenia b., Synechococcus sp., Pseudo
      Nitzchia, and Alexandrium. The effect of the sheath-to-sample flow-rate ratio on
      the light scatter and fluorescence of these marine microorganisms was
      investigated. Reducing the sample flow rate from 200 MUL/min to 10 MUL/min
      produced a more tightly focused sample stream and less heterogeneous signals.

PMID- 22662032
TI  - A handheld preconcentrator for the rapid collection of cancerous cells using
      dielectrophoresis generated by circular microelectrodes in stepping electric
      fields.
AB  - The ability to concentrate biological cells, such as circulating tumor cells,
      circulating fetal cells, and stem cells, is an important issue in medical
      diagnostics and characterization. The present study develops a handheld device
      capable of effectively preconcentrating cancerous cells. Circular microelectrodes
      were designed to generate a stepping electric field by switching the electric
      field to an adjacent electrode pair by relays. Cancerous cells with a positive
      dielectrophoretic response are guided toward the center of the circular
      microelectrodes due to the region of high electric field between the adjacent
      electrodes being gradually decreased in the direction of the stepping electric
      field. Numerical simulations of the electric fields were performed to demonstrate
      the concept of the proposed design. The preconcentration of HeLa cells, which are
      a human cervical carcinoma cell line, was achieved in 160 s with an efficiency of
      around 76%, with an applied peak-to-peak voltage of 16 V at a frequency of 1 MHz.

PMID- 22662033
TI  - Pheromone synthesis in a biomicroreactor coated with anti-adsorption
      polyelectrolyte multilayer.
AB  - To prepare a biosynthetic module in an infochemical communication project, we
      designed a silicon/glass microreactor with anti-adsorption polyelectrolyte
      multilayer coating and immobilized alcohol acetyl transferase (atf), one of the
      key biosynthetic enzymes of the pheromone of Spodoptera littoralis, on agarose
      beads inside. The system reproduces the last step of the biosynthesis in which
      the precursor diene alcohol (Z,E)-9,11-tetradecadienol is transformed into the
      major component (Z,E)-9,11-tetradecadienyl acetate. The scope of this study was
      to analyze and implement a multilayer, anti-adsorption coating based on layer-by
      layer deposition of polyethylenimine/dextransulfate sodium salt (PEI/DSS). The
      multilayers were composed of two PEI with molecular weights 750 and 1.2 kDa at pH
      9.2 or 6.0. Growth, morphology, and stability of the layers were analyzed by
      ellipsometry and atomic force microscopy (AFM). The anti-adsorption functionality
      of the multilayer inside the microreactor was validated. The activity of His(6)
      (atf) was measured by gas chromatography coupled to mass spectrometer (GC-MS).

PMID- 22662034
TI  - Measurement of fluid flow generated by artificial cilia.
AB  - We observed and measured the fluid flow that was generated by an artificial
      cilium. The cilium was composed of superparamagnetic microspheres, in which
      magnetic dipole moments were induced by an external magnetic field. The
      interaction between the dipole moments resulted in formation of long chains
      cilia, and the same external magnetic field was also used to drive the cilia in a
      periodic manner. Asymmetric periodic motion of the cilium resulted in generation
      of fluid flow and net pumping of the surrounding fluid. The flow and pumping
      performance were closely monitored by introducing small fluorescent tracer
      particles into the system. By detecting their motion, the fluid flow around an
      individual cilium was mapped and the flow velocities measured. We confirm that
      symmetric periodic beating of one cilium results in vortical motion only, whereas
      asymmetry is required for additional translational motion. We determine the
      effect of asymmetry on the pumping performance of a cilium, verify the
      theoretically predicted optimal pumping conditions, and determine the fluid
      behaviour around a linear array of three neighbouring cilia. In this case, the
      contributions of neighbouring cilia enhance the maximal flow velocity compared
      with a single cilium and contribute to a more uniform translational flow above
      the surface.

PMID- 22662035
TI  - Rapid formation of size-controlled three dimensional hetero-cell aggregates using
      micro-rotation flow for spheroid study.
AB  - Spheroids that are formed from aggregated cells have enhanced biological function
      compared to individual cells. In particular, hetero-spheroids composed of
      different types of cells, such as hepatocytes and endothelial cells, express
      tissue specific functions at a high level, which is advantageous for more precise
      drug screening and biological research. In this study, we propose rapid formation
      of size-controlled three-dimensional hetero-cell aggregates consisting of
      hepatocytes and endothelial cells using micro-rotation flow. Based on previous
      data, these aggregates are expected to ultimately become hetero-spheroids. The
      hepatocytes are coated with collagen gel films less than 200 nm thick, which were
      experimentally verified to increase adhesion strength between hepatocytes and
      endothelial cells. Gel-coated hepatocytes and endothelial cells are collected in
      an array by micro-rotational flow, thereby forming hetero-cell aggregates within
      2 min. This array allowed the size of the three-dimensional cell aggregates to be
      hydrodynamically controlled, with standard deviations of less than 19%, by
      varying the cell density of the medium without altering the device geometry.
      Endothelial cells were successfully and uniformly dispersed in the aggregates.
      The proposed microfluidic device, with its capability of rapidly forming size
      controlled hetero-cell aggregates, will offer an efficient experimental platform
      for future hetero-spheroid study that will contribute to drug screening and
      regenerative medicine.

PMID- 22662036
TI  - A self-contained polymeric cartridge for automated biological sample preparation.
AB  - Sample preparation is one of the most crucial processes for nucleic acids based
      disease diagnosis. Several steps are required for nucleic acids extraction,
      impurity washes, and DNA/RNA elution. Careful sample preparation is vital to the
      obtaining of reliable diagnosis, especially with low copies of pathogens and
      cells. This paper describes a low-cost, disposable lab cartridge for automatic
      sample preparation, which is capable of handling flexible sample volumes of 10
      MUl to 1 ml. This plastic cartridge contains all the necessary reagents for
      pathogen and cell lysis, DNA/RNA extraction, impurity washes, DNA/RNA elution and
      waste processing in a completely sealed cartridge. The entire sample preparation
      processes are automatically conducted within the cartridge on a desktop unit
      using a pneumatic fluid manipulation approach. Reagents transportation is
      achieved with a combination of push and pull forces (with compressed air and
      vacuum, respectively), which are connected to the pneumatic inlets at the bottom
      of the cartridge. These pneumatic forces are regulated by pinch valve manifold
      and two pneumatic syringe pumps within the desktop unit. The performance of this
      pneumatic reagent delivery method was examined. We have demonstrated the
      capability of the on-cartridge RNA extraction and cancer-specific gene
      amplification from 10 copies of MCF-7 breast cancer cells. The on-cartridge DNA
      recovery efficiency was 54-63%, which was comparable to or better than the
      conventional manual approach using silica spin column. The lab cartridge would be
      suitable for integration with lab-chip real-time polymerase chain reaction
      devices in providing a portable system for decentralized disease diagnosis.

PMID- 22662038
TI  - Complex three-dimensional high aspect ratio microfluidic network manufactured in
      combined PerMX dry-resist and SU-8 technology.
AB  - In this paper we present a new fabrication method that combines for the first
      time popular SU-8 technology and PerMX dry-photoresist lamination for the
      manufacturing of high aspect ratio three-dimensional multi-level microfluidic
      networks. The potential of this approach, which further benefits from wafer-level
      manufacturing and accurate alignment of fluidic levels, is demonstrated by a
      highly integrated three-level microfluidic chip. The hereby achieved network
      complexity, including 24 fluidic vias and 16 crossing points of three individual
      microchannels on less than 13 mm(2) chip area, is unique for SU-8 based fluidic
      networks. We further report on excellent process compatibility between SU-8 and
      PerMX dry-photoresist which results in high interlayer adhesion strength. The
      tight pressure sealing of a fluidic channel (0.5 MPa for 1 h) is demonstrated for
      150 MUm narrow SU-8/PerMX bonding interfaces.

PMID- 22662037
TI  - Three-dimensional diamagnetic particle deflection in ferrofluid microchannel
      flows.
AB  - Magnetic field-induced particle manipulation is a promising technique for
      biomicrofluidics applications. It is simple, cheap, and also free of fluid
      heating issues that accompany other common electric, acoustic, and optical
      methods. This work presents a fundamental study of diamagnetic particle motion in
      ferrofluid flows through a rectangular microchannel with a nearby permanent
      magnet. Due to their negligible magnetization relative to the ferrofluid,
      diamagnetic particles experience negative magnetophoresis and are repelled away
      from the magnet. The result is a three-dimensionally focused particle stream
      flowing near the bottom outer corner of the microchannel that is the farthest to
      the center of the magnet and hence has the smallest magnetic field. The effects
      of the particle's relative position to the magnet, particle size, ferrofluid flow
      rate, and concentration on this three-dimensional diamagnetic particle deflection
      are systematically studied. The obtained experimental results agree
      quantitatively with the predictions of a three-dimensional analytical model.

PMID- 22662039
TI  - Fabrication of a gel particle array in a microfluidic device for bioassays of
      protein and glucose in human urine samples.
AB  - This paper describes a simple method for fabricating a series of poly(ethylene
      glycol) diacrylate (PEG-DA) hydrogel microstructures inside microfluidic channels
      as probe for proteins and glucose. In order to demonstrate the feasibility of
      this newly developed system, bovine serum albumin (BSA) was chosen as a model
      protein. PEG microcolumns were used for the parallel detection of multiple
      components. Using tetrabromophenol blue (TBPB) and the horseradish
      peroxidase/glucose oxidase reaction system, bovine serum albumin (BSA) and
      glucose in human urine were detected by color changes. The color changes for BSA
      within a concentration range of 1-150 MUM, and glucose within a range of 50 mM-2
      M could be directly distinguished by eyes or precisely identified by optical
      microscope. To show the practicability of the gel particle array, protein and
      glucose concentrations of real human urine samples were determined, resulting in
      a good correlation with hospital analysis. Notably, only a 5 uL sample was needed
      for a parallel measurement of both analytes. Conveniently, no special readout
      equipment or power source was required during the diagnosis process, which is
      promising for an application in rapid point-of-care diagnosis.

PMID- 22662040
TI  - On-chip collection of particles and cells by AC electroosmotic pumping and
      dielectrophoresis using asymmetric microelectrodes.
AB  - The recent development of microfluidic "lab on a chip" devices requiring sample
      sizes <100 MUL has given rise to the need to concentrate dilute samples and trap
      analytes, especially for surface-based detection techniques. We demonstrate a
      particle collection device capable of concentrating micron-sized particles in a
      predetermined area by combining AC electroosmosis (ACEO) and dielectrophoresis
      (DEP). The planar asymmetric electrode pattern uses ACEO pumping to induce equal,
      quadrilateral flow directed towards a stagnant region in the center of the
      device. A number of system parameters affecting particle collection efficiency
      were investigated including electrode and gap width, chamber height, applied
      potential and frequency, and number of repeating electrode pairs and electrode
      geometry. The robustness of the on-chip collection design was evaluated against
      varying electrolyte concentrations, particle types, and particle sizes. These
      devices are amenable to integration with a variety of detection techniques such
      as optical evanescent waveguide sensing.

PMID- 22662041
TI  - Biosensing in a microelectrofluidic system using optical whispering-gallery mode
      spectroscopy.
AB  - Label-free detection of biomolecules using an optical whispering-gallery mode
      sensor in a microelectrofluidic channel is simulated. Negatively charged bovine
      serum albumin is considered as the model protein analyte. The analyte transport
      in aqueous solution is controlled by an externally applied electrical field. The
      finite element method is employed for solving the equations of the charged
      species transport, the Poisson equation of electric potential, the equations of
      conservation of momentum and energy, and the Helmholtz equations of
      electromagnetic waves. The adsorption process of the protein molecules on the
      microsensor head surface is monitored by the resonance frequency shifts.
      Frequency shift caused by temperature variation due to Joule heating is analyzed
      and found to be negligible. The induced shifts behave in a manner similar to
      Langmuir-like adsorption kinetics; but the time constant increases due to the
      presence of the external electrical field. A correlation of the frequency shift,
      the analyte feed concentration in the solution, and the applied voltage gradient
      is obtained, in which an excellent linear relationship between the frequency
      shift and the analyte concentration is revealed. The applied voltage gradient
      enhances significantly the analyte concentration in the vicinity of the sensor
      surface; thus, the sensor sensitivity which has a power function of the voltage
      gradient with exponent 2.85 in the controlled voltage range. Simulated detection
      of extremely low protein concentration to the pico-molar level is carried out.

PMID- 22662042
TI  - A microdevice for the creation of patent, three-dimensional endothelial cell
      based microcirculatory networks.
AB  - Microvascular network formation is a significant and challenging goal in the
      engineering of large three-dimensional artificial tissue structures. We show here
      the development of a fully patent, 3D endothelial cell (microvascular)
      microfluidic network that has a single inlet and outlet, created in only 28 h in
      a microdevice involving fluid flow equivalent to natural vasculature. Our
      microdevice features a tailored "multi-rung ladder" network, a stylized mimic of
      an arterial-to-venous pedicle, designed to also allow for systematic and
      reproducible cell seeding. Immunofluorescence staining revealed a highly
      contiguous endothelial monolayer (human umbilical vein endothelial cells)
      throughout the whole network after 24 h of continuous perfusion. This network
      persisted for up to 72 h of culture, providing a useful template from which the
      effects of surface chemistry, fluid flow, and environmental conditions on the
      development of artificial vascular networks ex vivo may be rapidly and robustly
      evaluated.

PMID- 22662043
TI  - Microbridge structures for uniform interval control of flowing droplets in
      microfluidic networks.
AB  - Precise temporal control of microfluidic droplets such as synchronization and
      combinatorial pairing of droplets is required to achieve a variety range of
      chemical and biochemical reactions inside microfluidic networks. Here, we present
      a facile and robust microfluidic platform enabling uniform interval control of
      flowing droplets for the precise temporal synchronization and pairing of
      picoliter droplets with a reagent. By incorporating microbridge structures
      interconnecting the droplet-carrying channel and the flow control channel, a
      fluidic pressure drop was derived between the two fluidic channels via the
      microbridge structures, reordering flowing droplets with a defined uniform
      interval. Through the adjustment of the control oil flow rate, the droplet
      intervals were flexibly and precisely adjustable. With this mechanism of droplet
      spacing, the gelation of the alginate droplets as well as control of the droplet
      interval was simultaneously achieved by additional control oil flow including
      calcified oleic acid. In addition, by parallel linking identical microfluidic
      modules with distinct sample inlet, controlled synchronization and pairing of two
      distinct droplets were demonstrated. This method is applicable to facilitate and
      develop many droplet-based microfluidic applications, including biological assay,
      combinatorial synthesis, and high-throughput screening.

PMID- 22662044
TI  - Efficient capture of circulating tumor cells with a novel immunocytochemical
      microfluidic device.
AB  - Ability to perform cytogenetic interrogations on circulating tumor cells (CTCs)
      from the blood of cancer patients is vital for progressing toward targeted,
      individualized treatments. CTCs are rare compared to normal (bystander) blood
      cells, found in ratios as low as 1:10(9). The most successful isolation
      techniques have been immunocytochemical technologies that label CTCs for
      separation based on unique surface antigens that distinguish them from normal
      bystander cells. The method discussed here utilizes biotin-tagged antibodies that
      bind selectively to CTCs. The antibodies are introduced into a suspension of
      blood cells intending that only CTCs will display surface biotin molecules. Next,
      the cell suspension is passed through a microfluidic channel that contains about
      9000 transverse, streptavidin coated posts. A CTC making contact with a post has
      the opportunity to engage in a biotin-streptavidin reaction that immobilizes the
      cell. Bystander blood cells remain in suspension and pass through the channel.
      The goal of the present study is to establish the technical performance of these
      channels as a function of antigen density and operating conditions, especially
      flow rate. At 18 MUL/min, over 70% of cells are captured at antigen densities
      greater than 30 000 sites/cell while 50% of cells are captured at antigen
      densities greater than 10 000. It is found that lower flow rates lead to
      decreasing cell capture probabilities, indicating that some streamlines develop
      which are never close enough to a post to allow cell-post contact. Future
      modeling and streamline studies using computational fluid dynamics software could
      aid in optimization of channel performance for capture of rare cells.

PMID- 22662045
TI  - A microfluidics assisted porous silicon array for optical label-free biochemical
      sensing.
AB  - A porous silicon (PSi) based microarray has been integrated with a microfluidic
      system, as a proof of concept device for the optical monitoring of selective
      label-free DNA-DNA interaction. A 4 * 4 square matrix of PSi one dimensional
      photonic crystals, each one of 200 MUm diameter and spaced by 600 MUm, has been
      sealed by a polydimethylsiloxane (PDMS) channels circuit. The PSi optical
      microarray elements have been functionalized by DNA single strands after sealing:
      the microfluidic circuit allows to reduce significantly the biologicals and
      chemicals consumption, and also the incubation time with respect to a not
      integrated device. Theoretical calculations, based on finite element method,
      taking into account molecular interactions, are in good agreement with the
      experimental results, and the developed numerical model can be used for device
      optimization. The functionalization process and the interaction between DNA probe
      and target has been monitored by spectroscopic reflectometry for each PSi element
      in the microchannels.

PMID- 22662046
TI  - A cell electrofusion microfluidic device integrated with 3D thin-film
      microelectrode arrays.
AB  - A microfluidic device integrated with 3D thin film microelectrode arrays wrapped
      around serpentine-shaped microchannel walls has been designed, fabricated and
      tested for cell electrofusion. Each microelectrode array has 1015 discrete
      microelectrodes patterned on each side wall, and the adjacent microelectrodes are
      separated by coplanar dielectric channel wall. The device was tested to
      electrofuse K562 cells under a relatively low voltage. Under an AC electric field
      applied between the pair of the microelectrode arrays, cells are paired at the
      edge of each discrete microelectrode due to the induced positive
      dielectrophoresis. Subsequently, electric pulse signals are sequentially applied
      between the microelectrode arrays to induce electroporation and electrofusion.
      Compared to the design with thin film microelectrode arrays deposited at the
      bottom of the side walls, the 3D thin film microelectrode array could induce
      electroporation and electrofusion under a lower voltage. The staggered electrode
      arrays on opposing side walls induce inhomogeneous electric field distribution,
      which could avoid multi-cell fusion. The alignment and pairing efficiencies of
      K562 cells in this device were 99% and 70.7%, respectively. The electric pulse of
      low voltage (~9 V) could induce electrofusion of these cells, and the fusion
      efficiency was about 43.1% of total cells loaded into the device, which is much
      higher than that of the convectional and most existing microfluidics-based
      electrofusion devices.

PMID- 22662047
TI  - Separation of platelets from other blood cells in continuous-flow by
      dielectrophoresis field-flow-fractionation.
AB  - We present a microfluidic device capable of separating platelets from other blood
      cells in continuous flow using dielectrophoresis field-flow-fractionation. The
      use of hydrodynamic focusing in combination with the application of a
      dielectrophoretic force allows the separation of platelets from red blood cells
      due to their size difference. The theoretical cell trajectory has been calculated
      by numerical simulations of the electrical field and flow speed, and is in
      agreement with the experimental results. The proposed device uses the so-called
      "liquid electrodes" design and can be used with low applied voltages, as low as
      10 V(pp). The obtained separation is very efficient, the device being able to
      achieve a very high purity of platelets of 98.8% with less than 2% cell loss. Its
      low-voltage operation makes it particularly suitable for point-of-care
      applications. It could further be used for the separation of other cell types
      based on their size difference, as well as in combination with other sorting
      techniques to separate multiple cell populations from each other.

PMID- 22662048
TI  - Organosilane deposition for microfluidic applications.
AB  - Treatment of surfaces to change the interaction of fluids with them is a critical
      step in constructing useful microfluidics devices, especially those used in
      biological applications. Silanization, the generic term applied to the formation
      of organosilane monolayers on substrates, is both widely reported in the
      literature and troublesome in actual application for the uninitiated. These
      monolayers can be subsequently modified to produce a surface of a specific
      functionality. Here various organosilane deposition protocols and some
      application notes are provided as a basis for the novice reader to construct
      their own silanization procedures, and as a practical resource to a broader range
      of techniques even for the experienced user.

PMID- 22662049
TI  - Low cost fabrication and assembly process for re-usable 3D polydimethylsiloxane
      (PDMS) microfluidic networks.
AB  - A method to easily manufacture and assemble a polydimethylsiloxane (PDMS) based
      microfluidic device is described. The method uses low cost materials and re
      usable laser cut polymethyl methacrylate (PMMA) parts. In addition, the thickness
      of PDMS layers can be controlled and both PDMS layer surfaces are flat, which
      allows for multi-layer PDMS structures to be assembled. The use of mechanical
      clamping to seal the structure allows for easy cleaning and re-use of the
      manufactured part as it can be taken apart at any time. In this way, selected
      layers can be re-used or replaced. The process described can be easily adopted
      and utilised without the need for any costly clean room facilities or equipment
      such as oxygen bonders, making it ideal for laboratories, universities, and
      classrooms exploring microfluidics applications.

PMID- 22662050
TI  - Partial transfection of cells using laminar flows in microchannels.
AB  - This manuscript describes a convenient method for partial transfection using a Y
      shaped microchannel polydimethylsiloxane (PDMS)-glass chip and on-chip cationic
      lipid-mediated transfection. Enhanced green fluorescent protein genes (pEGFP-N2)
      were introduced into the COS-7 cells cultured in half of the channel, while red
      fluorescent protein genes (pDsRed-N1) were introduced into the cells cultured in
      another half of the channel. This on-chip partial transfection technique provides
      an avenue for the spatial control of transfection. It is possible to use this
      technique to perform parallel transfection on chips in order to study cell
      behaviors under two or more gene transfections in the same culture.

PMID- 22662051
TI  - Fabrication of multi-layer polymeric micro-sieve having narrow slot pores with
      conventional ultraviolet-lithography and micro-fabrication techniques.
AB  - Fast detection of waterborne pathogens is important for securing the hygiene of
      drinking water. Detection of pathogens in water at low concentrations and minute
      quantities demands rapid and efficient enrichment methods in order to improve the
      signal-to-noise ratio of bio-sensors. We propose and demonstrate a low cost and
      rapid method to fabricate a multi-layer polymeric micro-sieve using conventional
      lithography techniques. The micro-fabricated micro-sieves are made of several
      layers of SU-8 photoresist using multiple coating and exposure steps and a single
      developing process. The obtained micro-sieves have good mechanical properties,
      smooth surfaces, high porosity (~40%), and narrow pore size distribution
      (coefficient of variation < 3.33%). Sample loading and back-flushing using the
      multi-layer micro-sieve resulted in more than 90% recovery of pathogens, which
      showed improved performance than current commercial filters.

PMID- 22662052
TI  - The microfluidic system for studies of carcinoma and normal cells interactions
      after photodynamic therapy (PDT) procedures.
AB  - This study reports on the use of a microsystem for evaluation of photodynamic
      therapy (PDT) procedures on the "mixed" (carcinoma-normal) cultures. Balb/3T3
      (normal mouse embryo) and A549 (human lung carcinoma) cells were tested in
      separated and "mixed" cultures. Interactions and migration of cells cultured
      together were observed. The PDT procedures were examined in the hybrid
      (PDMS/glass) microsystem which contains cell culture microchambers integrated
      with network of microchannels. We investigated that the number of dead cells
      after PDT procedures is dependent on the kind of cell culture. Moreover, the
      influence of the carcinoma cells on the viability of normal cells in the "mixed"
      culture was observed.

PMID- 22662053
TI  - Three-dimensional cellular focusing utilizing a combination of insulator-based
      and metallic dielectrophoresis.
AB  - Particle focusing in microfluidic devices is a necessary step in medical
      applications, such as detection, sorting, counting, and flow cytometry. This
      study proposes a microdevice that combines insulator-based and metal-electrode
      dielectrophoresis for the three-dimensional focusing of biological cells. Four
      insulating structures, which form an X pattern, are employed to confine the
      electric field in a conducting solution, thereby creating localized field minima
      in the microchannel. These electrodes, 56-MUm-wide at the top and bottom
      surfaces, are connected to one electric pole of the power source. The electrodes
      connected to the opposite pole, which are at the sides of the microchannel, have
      one of three patterns: planar, dual-planar, or three-dimensional. Therefore, low
      electric-field regions at the center of the microchannel are generated to
      restrain the viable HeLa cells with negative dielectrophoretic response. The
      array of insulating structures aforementioned is used to enhance the performance
      of confinement. According to numerical simulations, three-dimensional electrodes
      exhibit the best focusing performance, followed by dual-planar and planar
      electrodes. Experimental results reveal that increasing the strength of the
      applied electric field or decreasing the inlet flow rate significantly enhances
      focusing performance. The smallest width of focusing is 17 MUm for an applied
      voltage and an inlet flow rate of 35 V and 0.5 MUl/min, respectively. The effect
      of the inlet flow rate on focusing is insignificant for an applied voltage of 35
      V. The proposed design retains the advantages of insulator-based
      dielectrophoresis with a relatively low required voltage. Additionally,
      complicated flow controls are unnecessary for the three-dimensional focusing of
      cells.

PMID- 22662054
TI  - Effect of wall permittivity on electroviscous flow through a contraction.
AB  - The electroviscous flow at low Reynolds number through a two-dimensional slit
      contraction with electric double-layer overlap is investigated numerically for
      cases where the permittivity of the wall material is significant in comparison
      with the permittivity of the liquid. The liquid-solid interface is assumed to
      have uniform surface-charge density. It is demonstrated that a finite wall
      permittivity has a marked effect on the distribution of ions in and around the
      contraction, with a significant build-up of counter-ions observed at the back
      step. The development length of the flow increases substantially as the wall
      permittivity becomes significant, meaning that the electric double-layers require
      a longer distance to develop within the contraction. Consequently, there is a
      corresponding decrease in the hydrodynamic and electro-potential resistance
      caused by the contraction. The effect of wall-region width on the flow
      characteristics is also quantified, demonstrating that the development length
      increases with increasing wall-region width for widths up to 5 channel widths.

PMID- 22662055
TI  - Microfluidic droplet encapsulation of highly motile single zoospores for
      phenotypic screening of an antioomycete chemical.
AB  - Highly motile Phytophthora sojae (P. sojae) zoospores of an oomycete plant
      pathogen and antioomycete candidate chemicals were encapsulated into
      microdroplets. Random fast self-motion of P. sojae zoospores was overcome by
      choosing an appropriate flow rate for a zoospore suspension. To influence
      stochastic loading of zoospores into a microfluidic channel, a zoospore
      suspension was directly preloaded into a microtubing with a largely reduced inner
      diameter. A relatively high single zoospore encapsulation rate of 60.5% was
      achieved on a most trivial T-junction droplet generator platform, without
      involving any specially designed channel geometry. We speculated that spatial
      reduction in the diameter direction of microtubing added a degree of zoospore
      ordering in the longitudinal direction of microtubing and thus influenced
      positively to change the inherent limitation of stochastic encapsulation of
      zoospores. Comparative phenotypic study of a plant oomycete pathogen at a single
      zoospore level had not been achieved earlier. Phenotypic changes of zoospores
      responding to various chemical concentration conditions were measured in multiple
      droplets in parallel, providing a reliable data set and thus an improved
      statistic at a low chemical consumption. Since each droplet compartment contained
      a single zoospore, we were able to track the germinating history of individual
      zoospores without being interfered by other germinating zoospores, achieving a
      high spatial resolution. By adapting some existing droplet immobilization and
      concentration gradient generation techniques, the droplet approach could
      potentially lead to a medium-to-high throughput, reliable screening assay for
      chemicals against many other highly motile zoospores of pathogens.

PMID- 22662056
TI  - Transportation of single cell and microbubbles by phase-shift introduced to
      standing leaky surface acoustic waves.
AB  - A microfluidic device was developed to precisely transport a single cell or
      multiple microbubbles by introducing phase-shifts to a standing leaky surface
      acoustic wave (SLSAW). The device consists of a polydimethyl-siloxane (PDMS)
      microchannel and two phase-tunable interdigital transducers (IDTs) for the
      generation of the relative phase for the pair of surface acoustic waves (SAW)
      propagating along the opposite directions forming a standing wave. When the SAW
      contacts the fluid medium inside the microchannel, some of SAW energy is coupled
      to the fluid and the SAW becomes the leaky surface wave. By modulating the
      relative phase between two IDTs, the positions of pressure nodes of the SLSAW in
      the microchannel change linearly resulting in the transportation of a single cell
      or microbubbles. The results also reveal that there is a good linear relationship
      between the relative phase and the displacement of a single cell or microbubbles.
      Furthermore, the single cell and the microbubbles can be transported over a
      predetermined distance continuously until they reach the targeted locations. This
      technique has its distinct advantages, such as precise position-manipulation,
      simple to implement, miniature size, and noninvasive character, which may provide
      an effective method for the position-manipulation of a single cell and
      microbubbles in many biological and biomedical applications.

PMID- 22662057
TI  - An insulator-based dielectrophoretic microdevice for the simultaneous filtration
      and focusing of biological cells.
AB  - Manipulating and discriminating biological cells of interest using microfluidic
      and micro total analysis system (MUTAS) devices have potential applications in
      clinical diagnosis and medicine. Cellular focusing in microfluidic devices is a
      prerequisite for medical applications, such as cell sorting, cell counting, or
      flow cytometry. In the present study, an insulator-based dielectrophoretic
      microdevice is designed for the simultaneous filtration and focusing of
      biological cells. The cells are introduced into the microchannel and
      hydrodynamically pre-confined by funnel-shaped insulating structures close to the
      inlet. There are ten sets of X-patterned insulating structures in the
      microfluidic channel. The main function of the first five sets of insulating
      structures is to guide the cells by negative dielectrophoretic responses (viable
      HeLa cells) into the center region of the microchannel. The positive
      dielectrophoretic cells (dead HeLa cells) are attracted to regions with a high
      electric-field gradient generated at the edges of the insulating structures. The
      remaining five sets of insulating structures are mainly used to focus negative
      dielectrophoretic cells that have escaped from the upstream region. Experiments
      employing a mixture of dead and viable HeLa cells are conducted to demonstrate
      the effectiveness of the proposed design. The results indicate that the
      performance of both filtration and focusing improves with the increasing strength
      of the applied electric field and a decreasing inlet sample flow rate, which
      agrees with the trend predicted by the numerical simulations. The filtration
      efficiency, which is quantitatively investigated, is up to 88% at an applied
      voltage of 50 V peak-to-peak (1 kHz) and a sample flow rate of 0.5 MUl/min. The
      proposed device can focus viable cells into a single file using a voltage of 35 V
      peak-to-peak (1 kHz) at a sample flow rate of 1.0 MUl/min.

PMID- 22662058
TI  - Simulation of conformational preconditioning strategies for electrophoretic
      stretching of DNA in a microcontraction.
AB  - We have used Brownian dynamics-finite element method to examine two
      conformational preconditioning approaches for improving DNA stretching in a
      microcontraction for the purpose of direct gene analysis. The newly proposed "pre
      stretching" strategy is found to significantly improve the degree of DNA
      extension at the exit of the contraction. On the other hand, applying an
      oscillating extensional field to DNA yields no preconditioning effect. Detailed
      analysis of the evolution of DNA extension and conformation reveals that the
      success of our "pre-stretching" strategy relies on the "non-local" effect that
      cannot be predicted using simple kinematics analysis. In other words, accurate
      prediction can only be obtained using detailed simulations. Comparing to the
      existing preconditioning strategies, our "pre-stretching" method is easy to
      implement while still providing a very good performance. We hope that the insight
      gained from this study can be useful for future design of biomicrofluidic devices
      for DNA manipulation.

PMID- 22662059
TI  - Manipulating particle trajectories with phase-control in surface acoustic wave
      microfluidics.
AB  - We present a 91 MHz surface acoustic wave resonator with integrated microfluidics
      that includes a flow focus, an expansion region, and a binning region in order to
      manipulate particle trajectories. We demonstrate the ability to change the
      position of the acoustic nodes by varying the electronic phase of one of the
      transducers relative to the other in a pseudo-static manner. The measurements
      were performed at room temperature with 3 MUm diameter latex beads dispersed in a
      water-based solution. We demonstrate the dependence of nodal position on pseudo
      static phase and show simultaneous control of 9 bead streams with spatial control
      of -0.058 MUm/deg +/- 0.001 MUm/deg. As a consequence of changing the position of
      bead streams perpendicular to their flow direction, we also show that the
      integrated acoustic-microfluidic device can be used to change the trajectory of a
      bead stream towards a selected bin with an angular control of 0.008 deg/deg +/-
      0.000(2) deg/deg.

PMID- 22662060
TI  - Contrast agent-free sonoporation: The use of an ultrasonic standing wave
      microfluidic system for the delivery of pharmaceutical agents.
AB  - Sonoporation is a useful biophysical mechanism for facilitating the transmembrane
      delivery of therapeutic agents from the extracellular to the intracellular
      milieu. Conventionally, sonoporation is carried out in the presence of ultrasound
      contrast agents, which are known to greatly enhance transient poration of
      biological cell membranes. However, in vivo contrast agents have been observed to
      induce capillary rupture and haemorrhage due to endothelial cell damage and to
      greatly increase the potential for cell lysis in vitro. Here, we demonstrate
      sonoporation of cardiac myoblasts in the absence of contrast agent (CA-free
      sonoporation) using a low-cost ultrasound-microfluidic device. Within this device
      an ultrasonic standing wave was generated, allowing control over the position of
      the cells and the strength of the acoustic radiation forces. Real-time single
      cell analysis and retrospective post-sonication analysis of insonated cardiac
      myoblasts showed that CA-free sonoporation induced transmembrane transfer of
      fluorescent probes (CMFDA and FITC-dextran) and that different mechanisms
      potentially contribute to membrane poration in the presence of an ultrasonic
      wave. Additionally, to the best of our knowledge, we have shown for the first
      time that sonoporation induces increased cell cytotoxicity as a consequence of CA
      free ultrasound-facilitated uptake of pharmaceutical agents (doxorubicin,
      luteolin, and apigenin). The US-microfluidic device designed here provides an in
      vitro alternative to expensive and controversial in vivo models used for early
      stage drug discovery, and drug delivery programs and toxicity measurements.

PMID- 22662061
TI  - Refinement of the theory for extracting cell dielectric properties from
      dielectrophoresis and electrorotation experiments.
AB  - A modified theory is proposed for extracting cell dielectric properties from the
      peak frequency measurement of electrorotation (ER) and the crossover frequency
      measurement of dielectrophoresis (DEP). Current theory in the literature is based
      on the low frequency (DC) approximations for the equivalent cell permittivity and
      conductivity, which are valid when the measurements are performed in a medium
      with conductivity less than 1 mS/m. The present theory extracts the cell
      properties through optimizing an expression for the medium conductivity in terms
      of the peak ER, or DEP crossover, frequency according to its definition using
      full expressions of equivalent cell permittivity and conductivity. Various levels
      of approximation of the theory are proposed and discussed through a scaling
      analysis. The present theory can extract both membrane and interior properties
      from the low and the high peak ER, or DEP crossover, frequencies for any medium
      conductivity provided the peak ER, or DEP crossover, frequency exists. It can be
      reduced to the linear theory for the low peak ER and DEP crossover frequencies in
      the literature when the medium conductivity is less than 10 mS/m. However, we can
      determine the membrane capacitance and conductance via the slope and intercept,
      respectively, of the straight line fitting of the ER peak and DEP frequency
      against medium conductivity data according to the linear theory only when the
      intercept dominates the experimental uncertainty, which occurs when the medium
      conductivity is less than 1 mS/m in practice.

PMID- 22662062
TI  - Optofluidic membrane interferometer: An imaging method for measuring microfluidic
      pressure and flow rate simultaneously on a chip.
AB  - We present a novel image-based method to measure the on-chip microfluidic
      pressure and flow rate simultaneously by using the integrated optofluidic
      membrane interferometers (OMIs). The device was constructed with two layers of
      structured polydimethylsiloxane (PDMS) on a glass substrate by multilayer soft
      lithography. The OMI consists of a flexible air-gap optical cavity which upon
      illumination by monochromatic light generates interference patterns that depends
      on the pressure. These interference patterns were captured with a microscope and
      analyzed by computer based on a pattern recognition algorithm. Compared with the
      previous techniques for pressure sensing, this method offers several advantages
      including low cost, simple fabrication, large dynamic range, and high
      sensitivity. For pressure sensing, we demonstrate a dynamic range of 0-10 psi
      with an accuracy of +/-2% of full scale. Since multiple OMIs can be integrated
      into a single chip for detecting pressures at multiple locations simultaneously,
      we also demonstrated a microfluidic flow sensing by measuring the differential
      pressure along a channel. Thanks to the simple fabrication that is compatible
      with normal microfluidics, such OMIs can be easily integrated into other
      microfluidic systems for in situ fluid monitoring.

PMID- 22662063
TI  - Influences of electric field on living cells in a charged water-in-oil droplet
      under electrophoretic actuation.
AB  - We experimentally investigate the effects of high electric field on living cells
      inside a charged droplet under electrophoretic actuation. When an aqueous droplet
      suspended in a dielectric liquid contacts with electrified electrode, the droplet
      acquires charge. This charged droplet undergoes electrophoretic motion under
      strong electric field (1-3 kV/cm), which can be used as a droplet manipulation
      method in biomicrofluidic applications. However, because strong electric field
      and use of dielectric oil can be a harmful environment for living cells, the
      biological feasibilities have been tested. Trypan blue test and cell growth test
      have been performed to check the viability and proliferation of cells in a
      droplet under various electric field strengths and actuation times. We have not
      observed any noticeable influence of electric field and silicone oil on the
      viability and proliferation of cells, which indicates that electrophoresis could
      be safely used as a manipulation method for a droplet containing living
      biological system.

PMID- 22662064
TI  - Growth propagation of yeast in linear arrays of microfluidic chambers over many
      generations.
AB  - The growth of microorganisms is often confined in restricting geometries. In this
      work, we designed a device to study the growth propagation of budding yeast along
      linear arrays of microfluidic chambers. Vacuum assisted cell loading was used to
      seed cells of limited numbers in the up-most chambers of each linear array. Once
      loaded, cells grow until confluent and then overgrow, pushing some of the
      newborns into the neighboring downstream chamber through connection channels.
      Such a scenario repeats sequentially along the whole linear chamber arrays. We
      observed that the propagation speed of yeast population along the linear arrays
      was strongly channel geometry dependent. When the connection channel is narrow
      and long, the amount of cells delivered into the downstream chamber is small so
      that cells grow over several generations in the same chamber before passing into
      the next chamber. Consequently, a population growth of more than 50 generations
      could be observed along a single linear array. We also provided a mathematical
      model to quantitatively interpret the observed growth dynamics.

PMID- 22662065
TI  - Membrane-integrated microfluidic device for high-resolution live cell imaging.
AB  - The design and fabrication of a membrane-integrated microfluidic cell culture
      device (five layers,<=500 MUm total thickness) developed for high resolution
      microscopy is reported here. The multi-layer device was constructed to enable
      membrane separated cell culture for tissue mimetic in vitro model applications
      and pharmacodynamic evaluation studies. The microdevice was developed via a
      unique combination of low profile fluidic interconnect design, substrate transfer
      methodology, and wet silane bonding. To demonstrate the unique high resolution
      imaging capability of this device, we used oil immersion microscopy to image
      stained nuclei and mitochondria in primary hepatocytes adhered to the
      incorporated membrane.

PMID- 22662066
TI  - Sealing SU-8 microfluidic channels using PDMS.
AB  - A simple method of irreversibly sealing SU-8 microfluidic channels using PDMS is
      reported in this paper. The method is based on inducing a chemical reaction
      between PDMS and SU-8 by first generating amino groups on PDMS surface using N(2)
      plasma treatment, then allowing the amino groups to react with the residual epoxy
      groups on SU-8 surface at an elevated temperature. The N(2) plasma treatment of
      PDMS can be conducted using an ordinary plasma chamber and high purity N(2),
      while the residual epoxy groups on SU-8 surface can be preserved by post-exposure
      baking SU-8 at a temperature no higher than 95  degrees C. The resultant chemical
      bonding between PDMS and SU-8 using the method create an interface that can
      withstand a stress that is greater than the bulk strength of PDMS. The bond is
      permanent and is long-term resistant to water. The method was applied in
      fabricating SU-8 microfluidi-photonic integrated devices, and the obtained
      devices were tested to show desirable performance.

PMID- 22662067
TI  - A perspective on paper-based microfluidics: Current status and future trends.
AB  - "Paper-based microfluidics" or "lab on paper," as a burgeoning research field
      with its beginning in 2007, provides a novel system for fluid handling and fluid
      analysis for a variety of applications including health diagnostics,
      environmental monitoring as well as food quality testing. The reasons why paper
      becomes an attractive substrate for making microfluidic systems include: (1) it
      is a ubiquitous and extremely cheap cellulosic material; (2) it is compatible
      with many chemical/biochemical/medical applications; and (3) it transports
      liquids using capillary forces without the assistance of external forces. By
      building microfluidic channels on paper, liquid flow is confined within the
      channels, and therefore, liquid flow can be guided in a controlled manner. A
      variety of 2D and even 3D microfluidic channels have been created on paper, which
      are able to transport liquids in the predesigned pathways on paper. At the
      current stage of its development, paper-based microfluidic system is claimed to
      be low-cost, easy-to-use, disposable, and equipment-free, and therefore, is a
      rising technology particularly relevant to improving the healthcare and disease
      screening in the developing world, especially for those areas with no- or low
      infrastructure and limited trained medical and health professionals. The research
      in paper-based microfluidics is experiencing a period of explosion; most
      published works have focused on: (1) inventing low-cost and simple fabrication
      techniques for paper-based microfluidic devices; and (2) exploring new
      applications of paper-based microfluidics by incorporating efficient detection
      methods. This paper aims to review both the fabrication techniques and
      applications of paper-based microfluidics reported to date. This paper also
      attempts to convey to the readers, from the authors' point of view the current
      limitations of paper-based microfluidics which require further research, and a
      few perspective directions this new analytical system may take in its
      development.

PMID- 22662068
TI  - Preface to special topic: selected papers from the second conference on advances
      in microfluidics and nanofluidics and Asia-pacific international symposium on lab
      on chip.

PMID- 22662069
TI  - Efficient manipulation of microparticles in bubble streaming flows.
AB  - Oscillating microbubbles of radius 20-100 MUm driven by ultrasound initiate a
      steady streaming flow around the bubbles. In such flows, microparticles of even
      smaller sizes (radius 1-5 MUm) exhibit size-dependent behaviors: particles of
      different sizes follow different characteristic trajectories despite density
      matching. Adjusting the relative strengths of the streaming flow and a
      superimposed Poiseuille flow allows for a simple tuning of particle behavior,
      separating the trajectories of particles with a size resolution on the order of 1
      MUm. Selective trapping, accumulation, and release of particles can be achieved.
      We show here how to design bubble microfluidic devices that use these concepts to
      filter, enrich, and preconcentrate particles of selected sizes, either by
      concentrating them in discrete clusters (localized both stream- and spanwise) or
      by forcing them into narrow, continuous trajectory bundles of strong spanwise
      localization.

PMID- 22662070
TI  - Cell separation and transportation between two miscible fluid streams using
      ultrasound.
AB  - This paper presents a two-stream microfluidic system for transporting cells or
      micro-sized particles from one fluid stream to another by acoustophoresis. The
      two fluid streams, one being the original suspension and the other being the
      destination fluid, flow parallel to each other in a microchannel. Using a half
      wave acoustic standing wave across the channel width, cells or particles with
      positive acoustic contrast factors are moved to the destination fluid where the
      pressure nodal line lies. By controlling the relative flow rate of the two fluid
      streams, the pressure nodal line can be maintained at a specific offset from the
      fluid interface within the destination fluid. Using this transportation method,
      particles or cells of different sizes and mechanical properties can be separated.
      The cells experiencing a larger acoustic radiation force are separated and
      transported from the original suspension to the destination fluid stream. The
      other particles or cells experiencing a smaller acoustic radiation force continue
      flowing in the original solution. Experiments were conducted to demonstrate the
      effective separation of polystyrene microbeads of different sizes (3 MUm and 10
      MUm) and waterborne parasites (Giardia lamblia and Cryptosporidium parvum).
      Diffusion occurs between the two miscible fluids, but it was found to have little
      effects on the transport and separation process, even when the two fluids have
      different density and speed of sound.

PMID- 22662071
TI  - Studying enzymatic bioreactions in a millisecond microfluidic flow mixer.
AB  - In this study, the pre-steady state development of enzymatic bioreactions using a
      microfluidic mixer is presented. To follow such reactions fast mixing of reagents
      (enzyme and substrate) is crucial. By using a highly efficient passive micromixer
      based on multilaminar flow, mixing times in the low millisecond range are
      reached. Four lamination layers in a shallow channel reduce the diffusion lengths
      to a few micrometers only, enabling very fast mixing. This was proven by confocal
      fluorescence measurements in the channel's cross sectional area. Adjusting the
      overall flow rate in the 200 MUm wide and 900 MUm long mixing and observation
      channel makes it possible to investigate enzyme reactions over several seconds.
      Further, the device enables changing the enzyme/substrate ratio from 1:1 up to
      3:1, while still providing high mixing efficiency, as shown for the enzymatic
      hydrolysis using beta-galactosidase. This way, the early kinetics of the enzyme
      reaction at multiple enzyme/substrate concentrations can be collected in a very
      short time (minutes). The fast and easy handling of the mixing device makes it a
      very powerful and convenient instrument for millisecond temporal analysis of
      bioreactions.

PMID- 22662072
TI  - Development and validation of a low cost blood filtration element separating
      plasma from undiluted whole blood.
AB  - Clinical point of care testing often needs plasma instead of whole blood. As
      centrifugation is labor intensive and not always accessible, filtration is a more
      appropriate separation technique. The complexity of whole blood is such that
      there is still no commercially available filtration system capable of separating
      small sample volumes (10-100 MUl) at the point of care. The microfluidics
      research in blood filtration is very active but to date nobody has validated a
      low cost device that simultaneously filtrates small samples of whole blood and
      reproducibly recovers clinically relevant biomarkers, and all this in a limited
      amount of time with undiluted raw samples. In this paper, we show first that
      plasma filtration from undiluted whole blood is feasible and reproducible in a
      low-cost microfluidic device. This novel microfluidic blood filtration element
      (BFE) extracts 12 MUl of plasma from 100 MUl of whole blood in less than 10 min.
      Then, we demonstrate that our device is valid for clinical studies by measuring
      the adsorption of interleukins through our system. This adsorption is
      reproducible for interleukins IL6, IL8, and IL10 but not for TNFalpha. Hence, our
      BFE is valid for clinical diagnostics with simple calibration prior to performing
      any measurement.

PMID- 22662073
TI  - Characterization and separation of Cryptosporidium and Giardia cells using on
      chip dielectrophoresis.
AB  - Dielectrophoresis (DEP) has been shown to have significant potential for the
      characterization of cells and could become an efficient tool for rapid
      identification and assessment of microorganisms. The present work is focused on
      the trapping, characterization, and separation of two species of Cryptosporidium
      (C. parvum and C. muris) and Giardia lambia (G. lambia) using a microfluidic
      experimental setup. Cryptosporidium oocysts, which are 2-4 MUm in size and nearly
      spherical in shape, are used for the preliminary stage of prototype development
      and testing. G. lambia cysts are 8-12 MUm in size. In order to facilitate
      effective trapping, simulations were performed to study the effects of buffer
      conductivity and applied voltage on the flow and cell transport inside the DEP
      chip. Microscopic experiments were performed using the fabricated device and the
      real part of Clausius-Mossotti factor of the cells was estimated from critical
      voltages for particle trapping at the electrodes under steady fluid flow. The
      dielectric properties of the cell compartments (cytoplasm and membrane) were
      calculated based on a single shell model of the cells. The separation of C. muris
      and G. lambia is achieved successfully at a frequency of 10 MHz and a voltage of
      3 Vpp (peak to peak voltage).

PMID- 22662074
TI  - AC-dielectrophoretic characterization and separation of submicron and micron
      particles using sidewall AgPDMS electrodes.
AB  - The recent development of microfluidic "lab on a chip" devices requires the need
      to continuously separate submicron particles. Here, we present a PDMS
      microfluidic device with sidewall conducting PDMS (AgPDMS) composite electrodes
      capable of separating submicron particles in hydrodynamic flow. In particular,
      the device can service dual functions. First, the AgPDMS composite electrodes
      embedded in a sidewall of the device channel allow for performing AC
      dielectrophoretic (DEP) characterization through direct microscopic observation
      of particle behavior. Characterization experiments are carried out for numerous
      parameters including particle size, medium conductivity, and AC field frequency
      to reveal important dielectrophoresis DEP information in terms of the crossover
      frequency and positive/negative DEP behavior under specific frequencies. Second,
      the device offers an advantage that sidewall AgPDMS composite electrodes can
      produce strong DEP effects throughout the entire channel height, and thus the
      robustness of the on-chip particle separation is demonstrated for continuous
      separation in a flowing mixture of 0.5 and 5 MUm particles with 100% separation
      efficiency.

PMID- 22662075
TI  - Microfluidic fabrication of water-in-water (w/w) jets and emulsions.
AB  - We demonstrate the generation of water-in-water (w/w) jets and emulsions by
      combining droplet microfluidics and aqueous two-phase systems (ATPS). The
      application of ATPS in microfluidics has been hampered by the low interfacial
      tension between typical aqueous phases. The low tension makes it difficult to
      form w/w droplets with conventional droplet microfluidic approaches. We show that
      by mechanically perturbing a stable w/w jet, w/w emulsions can be prepared in a
      controlled and reproducible fashion. We also characterize the encapsulation
      ability of w/w emulsions and demonstrate that their encapsulation efficiency can
      be significantly enhanced by inducing formation of precipitates and gels at the
      w/w interfaces. Our work suggests a biologically and environmentally friendly
      platform for droplet microfluidics and establishes the potential of w/w droplet
      microfluidics for encapsulation-related applications.

PMID- 22662076
TI  - Effect of slippage on the thermocapillary migration of a small droplet.
AB  - We conduct a numerical investigation and analytical analysis of the effect of
      slippage on the thermocapillary migration of a small liquid droplet on a
      horizontal solid surface. The finite element method is employed to solve the
      Navier-Stokes equations coupled with the energy equation. The effect of the slip
      behavior on the droplet migration is determined by using the Navier slip
      condition at the solid-liquid boundary. The results indicate that the dynamic
      contact angles and the contact angle hysteresis of the droplet are strictly
      correlated to the slip coefficient. The enhancement of the slip length leads to
      an increase in the droplet migration velocity due to the enhancement of the net
      momentum of thermocapillary convection vortices inside the droplet. A larger
      contact angle leads to an increase in the migration velocity which in turn
      enlarges the rate of the droplet migration velocity to the slip length. There is
      good agreement between the analytical and the numerical results when the dynamic
      contact angle utilizes in the analytical approach obtained from the results of
      the numerical computation, and the static contact angle is smaller than 50
      degrees .

PMID- 22662077
TI  - Visualizing millisecond chaotic mixing dynamics in microdroplets: A direct
      comparison of experiment and simulation.
AB  - In order to fully explore and utilize the advantages of droplet-based
      microfluidics, fast, sensitive, and quantitative measurements are indispensable
      for the diagnosis of biochemical reactions in microdroplets. Here, we report an
      optical detection technique using two-photon fluorescence lifetime imaging
      microscopy, with an aligning-summing and non-fitting division method, to depict
      two-dimensional (2D) maps of mixing dynamics by chaotic advection in
      microdroplets with high temporal and spatial resolution. The mixing patterns of
      two dye solutions inside droplets were quantitatively and accurately measured.
      The mixing efficiency in a serpentine droplet mixer was also quantified and
      compared with the simulation data. The mapped chaotic mixing dynamics agree well
      with the numerical simulation and theoretical prediction. This quantitative
      characterization is potentially applicable to the real-time kinetic study of
      biological and chemical reactions in droplet-based microfluidic systems.

PMID- 22662078
TI  - Temperature-induced droplet coalescence in microchannels.
AB  - This paper reports a technique for temperature-induced merging of droplets in a
      microchannel. The multiphase system consists of water droplet and oil as the
      dispersed phase and the carrying continuous phase. A resistive heater provides
      heating in a rectangular merging chamber. The temperature of the chamber is
      controlled by the voltage applied to the heater. The merging process of two
      neighboring droplets was investigated with different applied voltage, flow rate
      ratio between water and oil and total flowrate. Merging is found to be effective
      at high flow rate ratio, high temperature, and low total flowrate. The presented
      technique could be used for merging and mixing in droplet-based lab-on-a-chip
      platforms.

PMID- 22662079
TI  - Integrated microfluidics system using surface acoustic wave and electrowetting on
      dielectrics technology.
AB  - This paper presents integrated microfluidic lab-on-a-chip technology combining
      surface acoustic wave (SAW) and electro-wetting on dielectric (EWOD). This
      combination has been designed to provide enhanced microfluidic functionality and
      the integrated devices have been fabricated using a single mask lithographic
      process. The integrated technology uses EWOD to guide and precisely position
      microdroplets which can then be actuated by SAW devices for particle
      concentration, acoustic streaming, mixing and ejection, as well as for sensing
      using a shear-horizontal wave SAW device. A SAW induced force has also been
      employed to enhance the EWOD droplet splitting function.

PMID- 22662080
TI  - Handling of artificial membranes using electrowetting-actuated droplets on a
      microfluidic device combined with integrated pA-measurements.
AB  - Artificial membranes, as a controllable environment, are an essential tool to
      study membrane proteins. Electrophysiology provides information about the ion
      transport mechanism across a membrane at the single-protein level. Unfortunately,
      high-throughput studies and screening are not accessible to electrophysiology
      because it is a set of not automated and technically delicate methods. Therefore,
      it is necessary to automate and parallelize electrophysiology measurement in
      artificial membranes. Here, we present a first step toward this goal: the
      fabrication and characterization of a microfluidic device integrating
      electrophysiology measurements and the handling of an artificial membrane which
      includes its formation, its displacement and the separation of its leaflets using
      electrowetting actuation of sub-MUL droplets. To validate this device, we
      recorded the insertion of a model porin, alpha-hemolysin.

PMID- 22662081
TI  - Electrowetting on dielectric driven droplet resonance and mixing enhancement in
      parallel-plate configuration.
AB  - This study experimentally verifies that the mixing process in a droplet can be
      enhanced by driving the droplet at resonant frequencies and at alternating
      driving frequencies using a parallel-plate electrowetting on dielectric device.
      The mixing time, which is defined as the time required for reaching the well
      mixed state, in a resonant droplet is found to be significantly shorter than that
      in a non-resonant droplet. Besides, it is also found that a higher driving
      potential leads to a better mixing effect, especially at resonant frequencies.
      Furthermore, when a droplet is driven by alternating two driving frequencies,
      especially two resonant frequencies, the mixing efficiency is found to be
      significantly enhanced for a specific alternating duration of these two
      frequencies.

PMID- 22662082
TI  - Manipulating liquid plugs in microchannel with controllable air vents.
AB  - An air venting element on microchannel, which can be controlled externally and
      automatically, was demonstrated for manipulating liquid plugs in microfluidic
      systems. The element's open and closed statuses correspond to the positioning and
      movement of a liquid plug in the microchannel. Positioning of multiple liquid
      plugs at an air venting element enabled the merging and mixing of the plugs.
      Besides these basic functions, other modes of liquid plug manipulations including
      plug partitioning, multiple plug mixing, and spacing adjustment between liquid
      plugs, were realized using combination of multiple elements. The structure,
      operation, and some functions of the element were demonstrated with a
      microfluidic chip application. The performances of the element including its
      failure modes, threshold flow rate, and structural optimization were also
      discussed.

PMID- 22662083
TI  - Direction dependence of displacement time for two-fluid electroosmotic flow.
AB  - Electroosmotic flow that involves one fluid displacing another fluid is commonly
      encountered in various microfludic applications and experiments, for example,
      current monitoring technique to determine zeta potential of microchannel. There
      is experimentally observed anomaly in such flow, namely, the displacement time is
      flow direction dependent, i.e., it depends if it is a high concentration fluid
      displacing a low concentration fluid, or vice versa. Thus, this investigation
      focuses on the displacement flow of two fluids with various concentration
      differences. The displacement time was determined experimentally with current
      monitoring method. It is concluded that the time required for a high
      concentration solution to displace a low concentration solution is smaller than
      the time required for a low concentration solution to displace a high
      concentration solution. The percentage displacement time difference increases
      with increasing concentration difference and independent of the length or width
      of the channel and the voltage applied. Hitherto, no theoretical analysis or
      numerical simulation has been conducted to explain this phenomenon. A numerical
      model based on finite element method was developed to explain the experimental
      observations. Simulations showed that the velocity profile and ion distribution
      deviate significantly from a single fluid electroosmotic flow. The distortion of
      ion distribution near the electrical double layer is responsible for the
      displacement time difference for the two different flow directions. The trends
      obtained from simulations agree with the experimental findings.

PMID- 22662084
TI  - Numerical study of dc-biased ac-electrokinetic flow over symmetrical electrodes.
AB  - This paper presents a numerical study of DC-biased AC-electrokinetic (DC-biased
      ACEK) flow over a pair of symmetrical electrodes. The flow mechanism is based on
      a transverse conductivity gradient created through incipient Faradaic reactions
      occurring at the electrodes when a DC-bias is applied. The DC biased AC electric
      field acting on this gradient generates a fluid flow in the form of vortexes. To
      understand more in depth the DC-biased ACEK flow mechanism, a phenomenological
      model is developed to study the effects of voltage, conductivity ratio, channel
      width, depth, and aspect ratio on the induced flow characteristics. It was found
      that flow velocity on the order of mm/s can be produced at higher voltage and
      conductivity ratio. Such rapid flow velocity is one of the highest reported in
      microsystems technology using electrokinetics.

PMID- 22662085
TI  - Integrated microfluidic chip for rapid DNA digestion and time-resolved capillary
      electrophoresis analysis.
AB  - An integrated microfluidic chip is proposed for rapid DNA digestion and time
      resolved capillary electrophoresis (CE) analysis. The chip comprises two gel
      filled chambers for DNA enrichment and purification, respectively, a T-form
      micromixer for DNA/restriction enzyme mixing, a serpentine channel for DNA
      digestion reaction, and a CE channel for on-line capillary electrophoresis
      analysis. The DNA and restriction enzyme are mixed electroomostically using a
      pinched-switching DC field. The experimental and numerical results show that a
      mixing performance of 97% is achieved within a distance of 1 mm from the T
      junction when a driving voltage of 90 V/cm and a switching frequency of 4 Hz are
      applied. Successive mixing digestion and capillary electrophoresis operation
      clearly present the changes on digesting phix-174 DNA in different CE runs. The
      time-resolved electropherograms show that the proposed device enables a phix-174
      DNA sample comprising 11 fragments to be concentrated and analyzed within 24 min.
      Overall, the results presented in this study show that the proposed microfluidic
      chip provides a rapid and effective tool for DNA digestion and CE analysis
      applications.

PMID- 22662086
TI  - Focused ion beam milling of microchannels in lithium niobate.
AB  - We present experimental and simulation results for focused ion beam (FIB) milling
      of microchannels in lithium niobate in this paper. We investigate two different
      cuts of lithium niobate, Y- and Z-cuts, and observe that the experimental
      material removal rate in the FIB for both Y-cut and Z-cut samples was 0.3
      MUm(3)/nC, roughly two times greater than the material removal rate previously
      reported in the literature but in good agreement with the value we obtain from
      stopping and range of ions in matter (SRIM) simulations. Further, we investigate
      the FIB milling rate and resultant cross-sectional profile of microchannels at
      various ion beam currents and find that the milling rate decreases as a function
      of ion dose and correspondingly, the cross-sectional profiles change from
      rectangular to V-shaped. This indicates that material redeposition plays an
      important role at high ion dose or equivalently, high aspect ratio. We find that
      the experimental material removal rate decreases as a function of aspect ratio of
      the milled structures, in good agreement with our simulation results at low
      aspect ratio and in good agreement with the material removal rates previously
      reported in the literature at high aspect ratios. Our results show that it is
      indeed easier than previously assumed to fabricate nanochannels with low aspect
      ratio directly on lithium niobate using the FIB milling technique.

PMID- 22662087
TI  - Investigation on CO(2) laser irradiation inducing glass strip peeling for
      microchannel formation.
AB  - The study investigates the use of CO(2) laser to induce glass strip peeling off
      to form microchannels on soda lime gass substrate. The strip peeling exhibits a
      strong dependence on the energy deposition rate on the glass surface. In spite of
      the vast difference in the combination of laser power and scanning speed, when
      the ratio of the two makes the energy deposition rate in the range 3.0-6.0
      J/(cm(2) s), the temperature rising inside glass will be above the strain point
      and reach the softening region of the glass. As a result, glass strip peeling is
      able to occur and form microchannels with dimensions of 20-40 MUm in depth and
      200-280 MUm in width on the glass surface. Beyond this range, higher energy
      depsotion rate would lead to surface melting associated with solidification
      cracks and lower energy deposition rate causes the generation of fragment cracks.

PMID- 22662088
TI  - Rapid and cost-effective fabrication of selectively permeable calcium-alginate
      microfluidic device using "modified" embedded template method.
AB  - In this paper, we have presented a non-lithographic embedded template method for
      rapid and cost-effective fabrication of a selectively permeable calcium-alginate
      (Ca-alginate) based microfluidic device with long serpentine delay channel. To
      demonstrate the versatility of the presented method, we have demonstrated two
      different strategies to fabricate serpentine long delay channels without using
      any sophisticated microfabrication techniques, in formal lab atmosphere. The
      procedure presented here, also, enables the preparation of a multilayered
      microfluidic device with channels of varying dimensions, in a single device
      without using any sophisticated micromachining instrumentation. In addition, we
      have also qualitatively studied the diffusion of small and large molecules from a
      Ca-alginate based microfluidic device and proposed a method to effectively
      control the out-flow of macro biomolecules from the crosslinked Ca-alginate
      matrix to create a selectively permeable matrix required for various biological
      and biomimetic applications, as mentioned in the Introduction section of this
      work.

PMID- 22662089
TI  - Cyclic olefin copolymer based microfluidic devices for biochip applications:
      Ultraviolet surface grafting using 2-methacryloyloxyethyl phosphorylcholine.
AB  - This report studies the surface modification of cyclic olefin copolymer (COC) by
      2-methacryloyloxyethyl phosphorylcholine (MPC) monomer using photografting
      technique for the purpose of biointerface applications, which demonstrate
      resistance to both protein adsorption and cell adhesion in COC-based microfluidic
      devices. This is essential because the hydrophobic nature of COC can lead to
      adsorption of specific compounds from biological fluids in the microchannel,
      which can affect the results during fluidic analysis and cause clogging inside
      the microchannel. A correlation was found between the irradiation time and
      hydrophobicity of the modified substrate. Static water contact angle results show
      that the hydrophilicity property of the MPC-grafted substrate improves with
      increasing irradiation time. The contact angle of the modified surface decreased
      to 20 +/- 5 degrees  from 88 +/- 3 degrees  for the untreated substrate. The
      surface characterization of the modified surface was evaluated using x-ray
      photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy
      (FTIR spectroscopy). Attenuated total reflection-FTIR and XPS results show the
      presence of the phosphate group (P-O) on modified COC substrates, indicating that
      the hydrophilic MPC monomer has successfully grafted on COC. Finally, it was
      demonstrated that cell adhesion and protein adsorption on the MPC modified COC
      specimen has reduced significantly.

PMID- 22662090
TI  - Resistive pulse sensing of magnetic beads and supraparticle structures using
      tunable pores.
AB  - Tunable pores (TPs) have been used for resistive pulse sensing of 1 MUm
      superparamagnetic beads, both dispersed and within a magnetic field. Upon
      application of this field, magnetic supraparticle structures (SPSs) were
      observed. Onset of aggregation was most effectively indicated by an increase in
      the mean event magnitude, with data collected using an automated thresholding
      method. Simulations enabled discrimination between resistive pulses caused by
      dimers and individual particles. Distinct but time-correlated peaks were often
      observed, suggesting that SPSs became separated in pressure-driven flow focused
      at the pore constriction. The distinct properties of magnetophoretic and pressure
      driven transport mechanisms can explain variations in the event rate when
      particles move through an asymmetric pore in either direction, with or without a
      magnetic field applied. Use of TPs for resistive pulse sensing holds potential
      for efficient, versatile analysis and measurement of nano- and microparticles,
      while magnetic beads and particle aggregation play important roles in many
      prospective biosensing applications.

PMID- 22662091
TI  - Microfluidic carbon-blackened polydimethylsiloxane device with reduced ultra
      violet background fluorescence for simultaneous two-color ultra violet/visible
      laser induced fluorescence detection in single cell analysis.
AB  - In single cell analysis (SCA), individual cell-specific properties and
      inhomogeneous cellular responses are being investigated that is not subjected to
      ensemble-averaging or heterogeneous cell population effects. For proteomic single
      cell analysis, ultra-sensitive and reproducible separation and detection
      techniques are essential. Microfluidic devices combined with UV laser induced
      fluorescence (UV-LIF) detection have been proposed to fulfill these requirements.
      Here, we report on a novel microfluidic chip fabrication procedure that combines
      straightforward production of polydimethylsiloxane (PDMS) chips with a reduced UV
      fluorescence background (83%-reduction) by using PDMS droplets with carbon black
      pigments (CBP) as additives. The CBP-droplet is placed at the point of detection,
      whereas the rest of the chip remains transparent, ensuring full optical control
      of the chip. We systematically studied the relation of the UV background
      fluorescence at CBP to PDMS ratios (varying from 1:10 to 1:1000) for different UV
      laser powers. Using a CBP/PDMS ratio of 1:20, detection of a 100 nM tryptophan
      solution (S/N = 3.5) was possible, providing a theoretical limit of detection of
      86 nM (with S/N = 3). Via simultaneous two color UV/VIS-LIF detection, we were
      able to demonstrate the electrophoretic separation of an analyte mixture of 500
      nM tryptophan (UV) and 5 nM fluorescein (VIS) within 30 s. As an application, two
      color LIF detection was also used for the electrophoretic separation of the
      protein content from a GFP-labeled single Spodoptera frugiperda (Sf9) insect
      cell. Thereby just one single peak could be measured in the visible spectral
      range that could be correlated with one single peak among others in the
      ultraviolet spectra. This indicates an identification of the labeled protein
      gamma-PKC and envisions a further feasible identification of more than one single
      protein in the future.

PMID- 22662092
TI  - Fluid flow due to collective non-reciprocal motion of symmetrically-beating
      artificial cilia.
AB  - Using a magneto-mechanical solid-fluid numerical model for permanently magnetic
      artificial cilia, we show that the metachronal motion of symmetrically beating
      cilia establishes a net pressure gradient in the direction of the metachronal
      wave, which creates a unidirectional flow. The flow generated is characterised as
      a function of the cilia spacing, the length of the metachronal wave, and a
      dimensionless parameter that characterises the relative importance of the viscous
      forces over the elastic forces in the cilia.

PMID- 22662093
TI  - Michaelis-Menten kinetics in shear flow: Similarity solutions for multi-step
      reactions.
AB  - Models for chemical reaction kinetics typically assume well-mixed conditions, in
      which chemical compositions change in time but are uniform in space. In contrast,
      many biological and microfluidic systems of interest involve non-uniform flows
      where gradients in flow velocity dynamically alter the effective reaction volume.
      Here, we present a theoretical framework for characterizing multi-step reactions
      that occur when an enzyme or enzymatic substrate is released from a flat solid
      surface into a linear shear flow. Similarity solutions are developed for
      situations where the reactions are sufficiently slow compared to a convective
      time scale, allowing a regular perturbation approach to be employed. For the
      specific case of Michaelis-Menten reactions, we establish that the transversally
      averaged concentration of product scales with the distance x downstream as
      x(5/3). We generalize the analysis to n-step reactions, and we discuss the
      implications for designing new microfluidic kinetic assays to probe the effect of
      flow on biochemical processes.

PMID- 22662094
TI  - High-throughput study of alpha-synuclein expression in yeast using microfluidics
      for control of local cellular microenvironment.
AB  - Microfluidics is an emerging technology which allows the miniaturization,
      integration, and automation of fluid handling processes. Microfluidic systems
      offer low sample consumption, significantly reduced processing time, and the
      prospect of massive parallelization. A microfluidic platform was developed for
      the control of the soluble cellular microenvironment of Saccharomyces cerevisiae
      cells, which enabled high-throughput monitoring of the controlled expression of
      alpha-synuclein (aSyn), a protein involved in Parkinson's disease. Y-shaped
      structures were fabricated using particle desorption mass spectrometry-based soft
      lithography techniques to generate biomolecular gradients along a microchannel.
      Cell traps integrated along the microchannel allowed the positioning and
      monitoring of cells in precise locations, where different, well-controlled
      chemical environments were established. S. cerevisiae cells genetically
      engineered to encode the fusion protein aSyn-GFP (green fluorescent protein)
      under the control of GAL1, a galactose inducible promoter, were loaded in the
      microfluidic structure. A galactose concentration gradient was established in the
      channel and a time-dependent aSyn-GFP expression was obtained as a function of
      the positioning of cells along the galactose gradient. Our results demonstrate
      the applicability of this microfluidic platform to the spatiotemporal control of
      cellular microenvironment and open a range of possibilities for the study of
      cellular processes based on single-cell analysis.

PMID- 22662095
TI  - A Laplace pressure based microfluidic trap for passive droplet trapping and
      controlled release.
AB  - Here, we present a microfluidic droplet trap that takes advantage of the net
      Laplace pressure force generated when a droplet is differentially constricted.
      Mathematical simulations were first used to understand the working range of the
      component; followed by finite element modeling using the CFD software package to
      further characterize the behavior of the system. Controlled release of the
      trapped droplets is also demonstrated through both a mechanical method and a
      chemical method that manipulates the total pressure exerted on the trapped
      droplet. The unique design of this trapping device also provides the capability
      for selection of a single droplet from a train, as well as droplet fusion.

PMID- 22662097
TI  - Dielectrophoretic capture voltage spectrum for measurement of dielectric
      properties and separation of cancer cells.
AB  - In this paper, a new dielectrophoresis (DEP) method based on capture voltage
      spectrum is proposed for measuring dielectric properties of biological cells. The
      capture voltage spectrum can be obtained from the balance of dielectrophoretic
      force and Stokes drag force acting on the cell in a microfluidic device with
      fluid flow and strip electrodes. The method was demonstrated with the measurement
      of dielectric properties of human colon cancer cells (HT-29 cells). From the
      capture voltage spectrum, the real part of Clausius-Mossotti factor of HT-29
      cells for different frequencies of applied electric field was obtained. The
      dielectric properties of cell interior and plasma membrane were then estimated by
      using single-shell dielectric model. The cell interior permittivity and
      conductivity were found to be insensitive to changes in the conductivity of the
      medium in which the cells are suspended, but the measured permittivity and
      conductivity of cell membrane were found to increase with the increase of medium
      conductivity. In addition, the measurement of capture voltage spectrum was found
      to be useful in providing the optimum operating conditions for separating HT-29
      cells from other cells (such as red blood cells) using dielectrophoresis.

PMID- 22662096
TI  - Hydrogel discs for digital microfluidics.
AB  - Hydrogels are networks of hydrophilic polymer chains that are swollen with water,
      and they are useful for a wide range of applications because they provide stable
      niches for immobilizing proteins and cells. We report here the marriage of
      hydrogels with digital microfluidic devices. Until recently, digital
      microfluidics, a fluid handling technique in which discrete droplets are
      manipulated electromechanically on the surface of an array of electrodes, has
      been used only for homogeneous systems involving liquid reagents. Here, we
      demonstrate for the first time that the cylindrical hydrogel discs can be
      incorporated into digital microfluidic systems and that these discs can be
      systematically addressed by droplets of reagents. Droplet movement is observed to
      be unimpeded by interaction with the gel discs, and gel discs remain stationary
      when droplets pass through them. Analyte transport into gel discs is observed to
      be identical to diffusion in cases in which droplets are incubated with gels
      passively, but transport is enhanced when droplets are continually actuated
      through the gels. The system is useful for generating integrated enzymatic
      microreactors and for three-dimensional cell culture. This paper demonstrates a
      new combination of techniques for lab-on-a-chip systems which we propose will be
      useful for a wide range of applications.

PMID- 22662098
TI  - Gravity-oriented microfluidic device for uniform and massive cell spheroid
      formation.
AB  - We propose a simple method for forming massive and uniform three-dimensional (3
      D) cell spheroids in a multi-level structured microfluidic device by
      gravitational force. The concept of orienting the device vertically has allowed
      spheroid formation, long-term perfusion, and retrieval of the cultured spheroids
      by user-friendly standard pipetting. We have successfully formed, perfused, and
      retrieved uniform, size-controllable, well-conditioned spheroids of human
      embryonic kidney 293 cells (HEK 293) in the gravity-oriented microfluidic device.
      We expect the proposed method will be a useful tool to study in-vitro 3-D cell
      models for the proliferation, differentiation, and metabolism of embryoid bodies
      or tumours.

PMID- 22662099
TI  - Induction of alternative fate other than default neuronal fate of embryonic stem
      cells in a membrane-based two-chambered microbioreactor by cell-secreted BMP4.
AB  - Cell-secreted soluble factor signaling in a diffusion dominant microenvironment
      plays an important role on early stage differentiation of pluripotent stem cells
      invivo. In this study, we utilized a membrane-based two-chambered microbioreactor
      (MB) to differentiate mouse embryonic stem cells (mESCs) in a diffusion dominant
      microenvironment of the top chamber while providing enough nutrient through the
      bottom chamber. Speculating that accumulated FGF4 in the small top chamber will
      augment neuronal differentiation in the MB culture, we first differentiated mESCs
      for 8 days by using a chemically optimized culture medium for neuronal induction.
      However, comparison of cellular morphology and expression of neuronal markers in
      the MB with that in the 6-well plate (6WP) indicated relatively lower neuronal
      differentiation in the MB culture. Therefore, to investigate whether
      microenvironment in the MB facilitates non-neuronal differentiation, we
      differentiated mESCs for 8 days by using chemically defined basal medium. In this
      case, differentiated cell morphology differed markedly between the MB and 6WP
      cultures: epithelial sheet-like morphology in the MB, whereas rosette morphology
      in the 6WP. Expression of markers from the three germ layers indicated lower
      neuronal but higher meso- and endo-dermal differentiation of mESCs in the MB than
      the 6WP culture. Moreover, among various cell-secreted soluble factors, BMP4
      expression was remarkably upregulated in the MB culture. Inhibition of BMP4
      signaling demonstrated that enhanced effect of upregulated BMP4 was responsible
      for the prominent meso- and endo-dermal differentiation in the MB. However, in
      the 6WP, downregulated BMP4 had a minimal influence on the differentiation
      behavior. Our study demonstrated utilization of a microbioreactor to modulate the
      effect of cell-secreted soluble factors by autoregulation and thereby inducing
      alternative self-capability of mESCs. Understanding and implementation of
      autoregulation of soluble factors similar to this study will lead to the
      development of robust culture systems to control ESC behavior.

PMID- 22662100
TI  - Rapid fabrication of a microdevice with concave microwells and its application in
      embryoid body formation.
AB  - Here, we report a novel method for the fabrication of polydimethylsiloxane
      microdevices with complicated 3-D structures, such as concave and crater shapes,
      using an easily machined polymethyl methacrylate mold combined with a one-step
      molding process. The procedure presented here enables rapid preparation of
      complex 3-D microstructures varying in shape and dimensions. To regulate embryoid
      body (EB) formation, we fabricated a microfluidic device with an array of concave
      microwells and found that EBs growing in microwells maintained their shape,
      viability, and a high degree of homogeneity. We believe that this novel method
      provides an alternative for rapid prototyping, especially in fabricating devices
      with curved 3-D microstructures.

PMID- 22662101
TI  - A practical guide for the fabrication of microfluidic devices using glass and
      silicon.
AB  - This paper describes the main protocols that are used for fabricating
      microfluidic devices from glass and silicon. Methods for micropatterning glass
      and silicon are surveyed, and their limitations are discussed. Bonding methods
      that can be used for joining these materials are summarized and key process
      parameters are indicated. The paper also outlines techniques for forming
      electrical connections between microfluidic devices and external circuits. A
      framework is proposed for the synthesis of a complete glass/silicon device
      fabrication flow.

PMID- 22662107
TI  - Identification of gene modules associated with drought response in rice by
      network-based analysis.
AB  - Understanding the molecular mechanisms that underlie plant responses to drought
      stress is challenging due to the complex interplay of numerous different genes.
      Here, we used network-based gene clustering to uncover the relationships between
      drought-responsive genes from large microarray datasets. We identified 2,607 rice
      genes that showed significant changes in gene expression under drought stress;
      1,392 genes were highly intercorrelated to form 15 gene modules. These drought
      responsive gene modules are biologically plausible, with enrichments for genes in
      common functional categories, stress response changes, tissue-specific expression
      and transcription factor binding sites. We observed that a gene module (referred
      to as module 4) consisting of 134 genes was significantly associated with drought
      response in both drought-tolerant and drought-sensitive rice varieties. This
      module is enriched for genes involved in controlling the response of the plant to
      water and embryonic development, including a heat shock transcription factor as
      the key regulator in the expression of ABRE-containing genes. These results
      suggest that module 4 is highly conserved in the ABA-mediated drought response
      pathway in different rice varieties. Moreover, our study showed that many hub
      genes clustered in rice chromosomes had significant associations with QTLs for
      drought stress tolerance. The relationship between hub gene clusters and drought
      tolerance QTLs may provide a key to understand the genetic basis of drought
      tolerance in rice.

PMID- 22662109
TI  - Fluctuation-driven flocking movement in three dimensions and scale-free
      correlation.
AB  - Recent advances in the study of flocking behavior have permitted more
      sophisticated analyses than previously possible. The concepts of "topological
      distances" and "scale-free correlations" are important developments that have
      contributed to this improvement. These concepts require us to reconsider the
      notion of a neighborhood when applied to theoretical models. Previous work has
      assumed that individuals interact with neighbors within a certain radius (called
      the "metric distance"). However, other work has shown that, assuming topological
      interactions, starlings interact on average with the six or seven nearest
      neighbors within a flock. Accounting for this observation, we previously proposed
      a metric-topological interaction model in two dimensions. The goal of our model
      was to unite these two interaction components, the metric distance and the
      topological distance, into one rule. In our previous study, we demonstrated that
      the metric-topological interaction model could explain a real bird flocking
      phenomenon called scale-free correlation, which was first reported by Cavagna et
      al. In this study, we extended our model to three dimensions while also
      accounting for variations in speed. This three-dimensional metric-topological
      interaction model displayed scale-free correlation for velocity and orientation.
      Finally, we introduced an additional new feature of the model, namely, that a
      flock can store and release its fluctuations.

PMID- 22662108
TI  - Autoantibody epitope spreading in the pre-clinical phase predicts progression to
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a prototypical autoimmune arthritis affecting nearly
      1% of the world population and is a significant cause of worldwide disability.
      Though prior studies have demonstrated the appearance of RA-related
      autoantibodies years before the onset of clinical RA, the pattern of immunologic
      events preceding the development of RA remains unclear. To characterize the
      evolution of the autoantibody response in the preclinical phase of RA, we used a
      novel multiplex autoantigen array to evaluate development of the anti
      citrullinated protein antibodies (ACPA) and to determine if epitope spread
      correlates with rise in serum cytokines and imminent onset of clinical RA. To do
      so, we utilized a cohort of 81 patients with clinical RA for whom stored serum
      was available from 1-12 years prior to disease onset. We evaluated the
      accumulation of ACPA subtypes over time and correlated this accumulation with
      elevations in serum cytokines. We then used logistic regression to identify a
      profile of biomarkers which predicts the imminent onset of clinical RA (defined
      as within 2 years of testing). We observed a time-dependent expansion of ACPA
      specificity with the number of ACPA subtypes. At the earliest timepoints, we
      found autoantibodies targeting several innate immune ligands including
      citrullinated histones, fibrinogen, and biglycan, thus providing insights into
      the earliest autoantigen targets and potential mechanisms underlying the onset
      and development of autoimmunity in RA. Additionally, expansion of the ACPA
      response strongly predicted elevations in many inflammatory cytokines including
      TNF-alpha, IL-6, IL-12p70, and IFN-gamma. Thus, we observe that the preclinical
      phase of RA is characterized by an accumulation of multiple autoantibody
      specificities reflecting the process of epitope spread. Epitope expansion is
      closely correlated with the appearance of preclinical inflammation, and we
      identify a biomarker profile including autoantibodies and cytokines which
      predicts the imminent onset of clinical arthritis.

PMID- 22662110
TI  - Central role of SREBP-2 in the pathogenesis of osteoarthritis.
AB  - BACKGROUND: Recent studies have implied that osteoarthritis (OA) is a metabolic
      disease linked to deregulation of genes involved in lipid metabolism and
      cholesterol efflux. Sterol Regulatory Element Binding Proteins (SREBPs) are
      transcription factors regulating lipid metabolism with so far no association with
      OA. Our aim was to test the hypothesis that SREBP-2, a gene that plays a key role
      in cholesterol homeostasis, is crucially involved in OA pathogenesis and to
      identify possible mechanisms of action. METHODOLOGY/PRINCIPAL FINDINGS: We
      performed a genetic association analysis using a cohort of 1,410 Greek OA
      patients and healthy controls and found significant association between single
      nucleotide polymorphism (SNP) 1784G>C in SREBP-2 gene and OA development.
      Moreover, the above SNP was functionally active, as normal chondrocytes'
      transfection with SREBP-2-G/C plasmid resulted in interleukin-1beta and
      metalloproteinase-13 (MMP-13) upregulation. We also evaluated SREBP-2, its target
      gene 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR), phospho
      phosphoinositide3-kinase (PI3K), phospho-Akt, integrin-alphaV (ITGAV) and
      transforming growth factor-beta (TGF-beta) mRNA and protein expression levels in
      osteoarthritic and normal chondrocytes and found that they were all significantly
      elevated in OA chondrocytes. To test whether TGF-beta alone can induce SREBP-2,
      we treated normal chondrocytes with TGF-beta and found significant upregulation
      of SREBP-2, HMGCR, phospho-PI3K and MMP-13. We also showed that TGF-beta
      activated aggrecan (ACAN) in chondrocytes only through Smad3, which interacts
      with SREBP-2. Finally, we examined the effect of an integrin inhibitor, cyclo
      RGDFV peptide, on osteoarthritic chondrocytes, and found that it resulted in
      significant upregulation of ACAN and downregulation of SREBP-2, HMGCR, phospho
      PI3K and MMP-13 expression levels. CONCLUSIONS/SIGNIFICANCE: We demonstrated, for
      the first time, the association of SREBP-2 with OA pathogenesis and provided
      evidence on the molecular mechanism involved. We suggest that TGF-beta induces
      SREBP-2 pathway activation through ITGAV and PI3K playing a key role in OA and
      that integrin blockage may be a potential molecular target for OA treatment.

PMID- 22662111
TI  - Polymorphisms in Toll-like receptors 2, 4, and 9 are highly associated with
      hearing loss in survivors of bacterial meningitis.
AB  - Genetic variation in innate immune response genes contributes to inter-individual
      differences in disease manifestation and degree of complications upon infection.
      We recently described an association of single nucleotide polymorphisms (SNPs) in
      TLR9 with susceptibility to meningococcal meningitis (MM). In this study, we
      investigate the association of SNPs in multiple pathogen recognition and immune
      response genes with clinical features that determine severity and outcome
      (especially hearing loss) of childhood MM and pneumococcal meningitis (PM).
      Eleven SNPs in seven genes (TLR2, TLR4, TLR9, NOD1, NOD2, CASP1, and TRAIL) were
      genotyped in 393 survivors of childhood bacterial meningitis (BM) (327 MM
      patients and 66 PM patients). Genotype distributions of single SNPs and
      combination of SNPs were compared between thirteen clinical characteristics
      associated with severity of BM. After correction for multiple testing, TLR4+896
      mutant alleles were highly associated with post-meningitis hearing loss,
      especially MM (p= 0.001, OR 4.0 for BM, p= 0.0004, OR 6.2 for MM). In a multigene
      analysis, combined carriership of the TLR2+2477 wild type (WT) with TLR4+896
      mutant alleles increases the risk of hearing loss (p<0.0001, OR 5.7 in BM and p=
      0.0001, OR 7.6 in MM). Carriage of one or both mutant alleles in TLR4+896 and
      TLR9 -1237 increases the risk for hearing loss (p = 0.0006, OR 4.1 in BM). SNPs
      in immune response genes contribute to differences in clinical severity and
      outcome of BM. The TLR system seems to play an important role in the immune
      response to BM and subsequent neuronal damage as well as in cochlear
      inflammation. Genetic markers may be used for identification of high-risk
      patients by creating prediction rules for post-meningitis hearing loss and other
      sequelae, and provide more insight in the complex immune response in the CNS
      possibly resulting in new therapeutic interventions.

PMID- 22662112
TI  - Auditory deficit as a consequence rather than endophenotype of specific language
      impairment: electrophysiological evidence.
AB  - BACKGROUND: Are developmental language disorders caused by poor auditory
      discrimination? This is a popular theory, but behavioural evidence has been
      inconclusive. Here we studied children with specific language impairment,
      measuring the brain's electrophysiological response to sounds in a passive
      paradigm. We focused on the T-complex, an event-related peak that has different
      origins and developmental course from the well-known vertex response. METHODS: We
      analysed auditory event-related potentials to tones and syllables from 16
      children and 16 adolescents with specific language impairment who were compared
      with 32 typically-developing controls, matched for gender, IQ and age. RESULTS:
      We replicated prior findings of significant reduction in Ta amplitude for both
      children and adolescents with specific language impairment, which was
      particularly marked for syllables. The topography of the T-complex to syllables
      indicated a less focal response in those with language impairments. To
      distinguish causal models, we considered correlations between size of the Ta
      response and measures of language and literacy in parents as well as children.
      The best-fitting model was one in which auditory deficit was a consequence rather
      than a cause of difficulties in phonological processing. CONCLUSIONS: The T
      complex to syllables has abnormal size and topography in children with specific
      language impairment, but this is more likely to be a consequence rather than a
      cause of difficulties in phonological processing.

PMID- 22662113
TI  - Evaluation of a screening instrument for autism spectrum disorders in prisoners.
AB  - There have been concerns that individuals with autism spectrum disorders (ASDs)
      are over-represented but not recognised in prison populations. A screening tool
      for ASDs in prisons has therefore been developed. AIMS: We aimed to evaluate this
      tool in Scottish prisoners by comparing scores with standard measures of autistic
      traits (Autism Quotient (AQ)), neurodevelopmental history (Asperger Syndrome (and
      High-Functioning Autism) Diagnostic Interview (ASDI)), and social cognition
      (Ekman 60 Faces test). METHODS: Prison officers across all 12 publicly-run closed
      prisons in Scotland assessed convicted prisoners using the screening tool. This
      sample included male and female prisoners and both adult and young offenders.
      Prisoners with high scores, along with an equal number of age and sex-matched
      controls, were invited to take part in interviews. Prisoners' relatives were
      contacted to complete a neurodevelopmental assessment. RESULTS: 2458 prisoners
      were screened using the tool, and 4% scored above the cut-off. 126 prisoners were
      further assessed using standardised measures. 7 of those 126 assessed scored 32
      or above (cut-off) on the AQ. 44 interviews were completed with prisoners'
      relatives, no prisoner reached the cut-off score on the ASDI. Scores on the
      screening tool correlated significantly with AQ and ASDI scores, and not with the
      Ekman 60 Faces Test or IQ. Sensitivity was 28.6% and specificity 75.6%; AUC was
      59.6%. CONCLUSIONS: Although this screening tool measures autistic traits in this
      population, sensitivity for scores of 32 or above on the AQ is poor. We consider
      that this limits its usefulness and do not recommend that the tool is routinely
      used to screen for ASDs in prisons.

PMID- 22662114
TI  - Bisphenol A-mediated suppression of LPL gene expression inhibits triglyceride
      accumulation during adipogenic differentiation of human adult stem cells.
AB  - The endocrine disrupting chemical, bisphenol A (BPA), has been shown to
      accelerate the rate of adipogenesis and increase the amount of triglyceride
      accumulation during differentiation of 3T3-L1 preadipocytes. The objective of
      this study was to investigate if that observation is mirrored in human primary
      cells. Here we investigated the effect of BPA on adipogenesis in cultured human
      primary adult stem cells. Continuous exposure to BPA throughout the 14 days of
      differentiation dramatically reduced triglyceride accumulation and suppressed
      gene transcription of the lipogenic enzyme, lipoprotein lipase (LPL). Results
      presented in the present study show for the first time that BPA can reduce
      triglyceride accumulation during adipogenesis by attenuating the expression of
      LPL gene transcription. Also, by employing image cytometric analysis rather than
      conventional Oil red O staining techniques we show that BPA regulates
      triglyceride accumulation in a manner which does not appear to effect
      adipogenesis per se.

PMID- 22662115
TI  - Variable carbon catabolism among Salmonella enterica serovar Typhi isolates.
AB  - BACKGROUND: Salmonella enterica serovar Typhi (S. Typhi) is strictly a human
      intracellular pathogen. It causes acute systemic (typhoid fever) and chronic
      infections that result in long-term asymptomatic human carriage. S. Typhi
      displays diverse disease manifestations in human infection and exhibits high
      clonality. The principal factors underlying the unique lifestyle of S. Typhi in
      its human host during acute and chronic infections remain largely unknown and are
      therefore the main objective of this study. METHODOLOGY/PRINCIPAL FINDINGS: To
      obtain insight into the intracellular lifestyle of S. Typhi, a high-throughput
      phenotypic microarray was employed to characterise the catabolic capacity of 190
      carbon sources in S. Typhi strains. The success of this study lies in the
      carefully selected library of S. Typhi strains, including strains from two
      geographically distinct areas of typhoid endemicity, an asymptomatic human
      carrier, clinical stools and blood samples and sewage-contaminated rivers. An
      extremely low carbon catabolic capacity (27% of 190 carbon substrates) was
      observed among the strains. The carbon catabolic profiles appeared to suggest
      that S. Typhi strains survived well on carbon subtrates that are found abundantly
      in the human body but not in others. The strains could not utilise plant
      associated carbon substrates. In addition, alpha-glycerolphosphate, glycerol, L
      serine, pyruvate and lactate served as better carbon sources to monosaccharides
      in the S. Typhi strains tested. CONCLUSION: The carbon catabolic profiles suggest
      that S. Typhi could survive and persist well in the nutrient depleted metabolic
      niches in the human host but not in the environment outside of the host. These
      findings serve as caveats for future studies to understand how carbon catabolism
      relates to the pathogenesis and transmission of this pathogen.

PMID- 22662116
TI  - Impact of sauropod dinosaurs on lagoonal substrates in the Broome Sandstone
      (Lower Cretaceous), Western Australia.
AB  - Existing knowledge of the tracks left by sauropod dinosaurs (loosely
      'brontosaurs') is essentially two-dimensional, derived mainly from footprints
      exposed on bedding planes, but examples in the Broome Sandstone (Early
      Cretaceous) of Western Australia provide a complementary three-dimensional
      picture showing the extent to which walking sauropods could deform the ground
      beneath their feet. The patterns of deformation created by sauropods traversing
      thinly-stratified lagoonal deposits of the Broome Sandstone are unprecedented in
      their extent and structural complexity. The stacks of transmitted reliefs
      (underprints or ghost prints) beneath individual footfalls are nested into a
      hierarchy of deeper and more inclusive basins and troughs which eventually attain
      the size of minor tectonic features. Ultimately the sauropod track-makers
      deformed the substrate to such an extent that they remodelled the topography of
      the landscape they inhabited. Such patterns of substrate deformation are revealed
      by investigating fragmentary and eroded footprints, not by the conventional
      search for pristine footprints on intact bedding planes. For that reason it is
      not known whether similar patterns of substrate deformation might occur at
      sauropod track-sites elsewhere in the world.

PMID- 22662117
TI  - Ginkgolide B reduces atherogenesis and vascular inflammation in ApoE(-/-) mice.
AB  - AIMS: To investigate whether ginkgolide B (a platelet-activating factor
      inhibitor) affects vascular inflammation in atherosclerosis-prone apolipoprotein
      E-deficient (ApoE(-/-)) mice. METHODS AND RESULTS: Human platelets were used to
      evaluate the effects of ginkgolide B on platelet aggregation and signal
      transduction. Ginkgolide B attenuated platelet aggregation and inhibited
      phosphatidylinositol 3 kinase (PI3K) activation and Akt phosphorylation in
      thrombin- and collagen-activated platelets. ApoE(-/-) mice were administered a
      high-cholesterol diet for 8 weeks. Plasma platelet factor 4 (PF4) and RANTES
      (regulated upon activation, normal T-cell expressed, and secreted protein) were
      then measured using an enzyme-linked immunosorbent assay. Scanning electron
      microscopy and immunohistochemistry were used to determine atherosclerotic
      lesions. Ginkgolide B decreased plasma PF4 and RANTES levels in ApoE(-/-) mice.
      Scanning electron microscopic examination showed that ginkgolide B reduced aortic
      plaque in ApoE(-/-) mice. Immunohistochemistry analysis demonstrated that
      ginkgolide B diminished P-selectin, PF4, RANTES, and CD40L expression in aortic
      plaque in ApoE(-/-) mice. Moreover, ginkgolide B suppressed macrophage and
      vascular cell adhesion protein 1 (VCAM-1) expression in aorta lesions in ApoE(-/
      ) mice. Similar effects were observed in aspirin-treated ApoE(-/-) mice.
      CONCLUSION: Ginkgolide B significantly reduced atherosclerotic lesions and P
      selectin, PF4, RANTES, and CD40L expression in aortic plaque in ApoE-/- mice. The
      efficacy of ginkgolide B was similar to aspirin. These results provide direct
      evidence that ginkgolide B inhibits atherosclerosis, which may be associated with
      inhibition of the PI3K/Akt pathway in activated platelets.

PMID- 22662118
TI  - The transmembrane region is responsible for targeting of adaptor protein LAX into
      "heavy rafts".
AB  - BACKGROUND: The importance of membrane compartmentalization into specific
      membrane microdomains has been shown in many biological processes such as
      immunoreceptor signaling, membrane trafficking, pathogen infection, and tumor
      progression. Microdomains like lipid rafts, caveolae and tetraspanin enriched
      microdomains are relatively resistant to solubilization by some detergents. Large
      detergent-resistant membrane fragments (DRMs) resulting from such membrane
      solubilization can be conveniently isolated by density gradient
      ultracentrifugation or gel filtration. Recently, we described a novel type of
      raft-like membrane microdomains producing, upon detergent Brij98 solubilization,
      "heavy DRMs" and containing a number of functionally relevant proteins.
      Transmembrane adaptor protein LAX is a typical "heavy raft" protein. The present
      study was designed to identify the molecular determinants targeting LAX-derived
      constructs to heavy rafts. METHODOLOGY/PRINCIPAL FINDINGS: We prepared several
      constructs encoding chimeric proteins containing various informative segments of
      the LAX sequence and evaluated their effects on targeting to heavy rafts.
      Replacement of the polybasic membrane-proximal part of LAX by CD3epsilon-derived
      membrane-proximal part had no effect on LAX solubilization. Similarly, the
      membrane-proximal part of LAX, when introduced into non-raft protein CD25 did not
      change CD25 detergent solubility. These results indicated that membrane-proximal
      part of LAX is not important for LAX targeting to heavy rafts. On the other hand,
      the replacement of transmembrane part of CD25 by the transmembrane part of LAX
      resulted in targeting into heavy rafts. We also show that LAX is not S-acylated,
      thus palmitoylation is not involved in LAX targeting to heavy rafts. Also,
      covalent dimerization was excluded as a cause of targeting into heavy rafts.
      CONCLUSIONS/SIGNIFICANCE: We identified the transmembrane domain of LAX as a
      first motif targeting transmembrane protein constructs to detergent-resistant
      heavy rafts, a novel type of membrane microdomains containing a number of
      physiologically important proteins.

PMID- 22662119
TI  - Risk factors for breast cancer and expression of insulin-like growth factor-2
      (IGF-2) in women with breast cancer in Wuhan City, China.
AB  - PURPOSE: The purpose of this study was to explore the risk factors for breast
      cancer and establish the expression rate of IGF-2 in female patients. METHODS: A
      case control study with 500 people in case group and 500 people in control group.
      A self-administered questionnaire was used to investigate risk factors for breast
      cancer. All cases were interviewed during a household survey. Immune
      histochemical method was used to inspect the expression of IGF-2 in different
      tissues (benign breast lesions, breast cancer and tumor-adjacent tissue).
      RESULTS: Multivariate adjusted odds ratios and 95% confidence intervals were
      calculated using unconditional logistic regression. High body mass index (OR =
      1.012,95%CI = 1.008-1.016), working attributes (OR = 1.004, 95%CI = 1.002 =
      1.006), long menstrual period (OR = 1.007, 95%CI = 1.005-1.009), high parity OR =
      1.003, 95%CI = 1.001-1.005) , frequent artificial abortion (OR = 1.004, 95%CI =
      1.001-1.005), family history of cancer (OR = 1.003, 95%CI = 1.000-1.005), period
      of night shift (OR = 1.003, 95%CI = 1.001-1.006), live in high risk environment
      (OR = 1.005, 95%CI = 1.002-1.008), and family problems (OR = 1.010, 95%CI = 1.005
      1.014) were associated with increased risk for breast cancer. In this study, good
      sleeping status, positive coping strategies, subjective support, and utility
      degree of social support were associated with reduced risk for breast cancer (OR
      = 0.998, 0.997, 0.985, 0.998 respectively; 95%CI = 0.996-1.000, 0.994-1.000,
      0.980-0.989, 0.996-1.000, respectively). In benign breast lesions, breast cancer
      and tumor-adjacent tissue, IGF-2 was mainly expressed in the cytoplasm, but its
      expression rate was different (p<0.05). CONCLUSIONS: The incidence of breast
      cancer is a common result of multiple factors. IGF-2 is involved in the
      development of breast cancer, and its expression varies in different tissues
      (benign breast lesions, breast cancer and tumor-adjacent tissue).

PMID- 22662120
TI  - Long branch effects distort maximum likelihood phylogenies in simulations despite
      selection of the correct model.
AB  - The aim of our study was to test the robustness and efficiency of maximum
      likelihood with respect to different long branch effects on multiple-taxon trees.
      We simulated data of different alignment lengths under two different 11-taxon
      trees and a broad range of different branch length conditions. The data were
      analyzed with the true model parameters as well as with estimated and incorrect
      assumptions about among-site rate variation. If length differences between
      connected branches strongly increase, tree inference with the correct likelihood
      model assumptions can fail. We found that incorporating invariant sites together
      with Gamma distributed site rates in the tree reconstruction (Gamma+I) increases
      the robustness of maximum likelihood in comparison with models using only Gamma.
      The results show that for some topologies and branch lengths the reconstruction
      success of maximum likelihood under the correct model is still low for alignments
      with a length of 100,000 base positions. Altogether, the high confidence that is
      put in maximum likelihood trees is not always justified under certain tree shapes
      even if alignment lengths reach 100,000 base positions.

PMID- 22662122
TI  - Insecticide-mediated apparent displacement between two invasive species of
      leafminer fly.
AB  - BACKGROUND: Closely related invasive species may often displace one another, but
      it is often difficult to determine mechanisms because of the historical nature of
      these events. The leafmining flies Liriomyza sativae and Liriomyza trifolii have
      become serious invasive agricultural pests throughout the world. Where both
      species have invaded the same region, one predominates over the other. Although
      L. sativae invaded Hainan Island of China first, it recently has been displaced
      by the newly invasive L. trifolii. We hypothesized that differential
      susceptibilities to insecticides could be causing this demographic shift.
      METHODOLOGY/PRINCIPAL FINDINGS: Avermectin and cyromazine are the most commonly
      used insecticides to manage leafminers, with laboratory bioassays demonstrating
      that L. trifolii is significantly less susceptible to these key insecticides than
      is L. sativae. In trials where similar numbers of larvae of both species infested
      plants, which subsequently were treated with the insecticides, the eclosing
      adults were predominately L. trifolii, yet similar numbers of adults of both
      species eclosed from control plants. The species composition was then surveyed in
      two regions where L. trifolii has just begun to invade and both species are still
      common. In field trials, both species occurred in similar proportions before
      insecticide treatments began. Following applications of avermectin and
      cyromazine, almost all eclosing adults were L. trifolii in those treatment plots.
      In control plots, similar numbers of adults of the two species eclosed, lending
      further credence to the hypothesis that differential insecticide susceptibilities
      could be driving the ongoing displacement of L. sativae by L. trifolii.
      CONCLUSIONS/SIGNIFICANCE: Our results show that differential insecticide
      susceptibility can lead to rapid shifts in the demographics of pest complexes.
      Thus, successful pest management requires the identification of pest species to
      understand the outcome of insecticide applications. These results further
      demonstrate the importance of considering anthropogenic factors in the outcome of
      interspecific interactions.

PMID- 22662121
TI  - Transposable-element associated small RNAs in Bombyx mori genome.
AB  - Small RNAs are a group of regulatory RNA molecules that control gene expression
      at transcriptional or post-transcriptional levels among eukaryotes. The silkworm,
      Bombyx mori L., genome harbors abundant repetitive sequences derived from
      families of retrotransposons and transposons, which together constitute almost
      half of the genome space and provide ample resource for biogenesis of the three
      major small RNA families. We systematically discovered transposable-element (TE)
      associated small RNAs in B. mori genome based on a deep RNA-sequencing strategy
      and the effort yielded 182, 788 and 4,990 TE-associated small RNAs in the miRNA,
      siRNA and piRNA species, respectively. Our analysis suggested that the three
      small RNA species preferentially associate with different TEs to create sequence
      and functional diversity, and we also show evidence that a Bombyx non-LTR
      retrotransposon, bm1645, alone contributes to the generation of TE-associated
      small RNAs in a very significant way. The fact that bm1645-associated small RNAs
      partially overlap with each other implies a possibility that this element may be
      modulated by different mechanisms to generate different products with diverse
      functions. Taken together, these discoveries expand the small RNA pool in B. mori
      genome and lead to new knowledge on the diversity and functional significance of
      TE-associated small RNAs.

PMID- 22662123
TI  - How to join a wave: decision-making processes in shimmering behavior of Giant
      honeybees (Apis dorsata).
AB  - Shimmering is a collective defence behaviour in Giant honeybees (Apis dorsata)
      whereby individual bees flip their abdomen upwards, producing Mexican wave-like
      patterns on the nest surface. Bucket bridging has been used to explain the spread
      of information in a chain of members including three testable concepts: first,
      linearity assumes that individual "agent bees" that participate in the wave will
      be affected preferentially from the side of wave origin. The directed-trigger
      hypothesis addresses the coincidence of the individual property of trigger
      direction with the collective property of wave direction. Second, continuity
      describes the transfer of information without being stopped, delayed or re
      routed. The active-neighbours hypothesis assumes coincidence between the
      direction of the majority of shimmering-active neighbours and the trigger
      direction of the agents. Third, the graduality hypothesis refers to the
      interaction between an agent and her active neighbours, assuming a proportional
      relationship in the strength of abdomen flipping of the agent and her previously
      active neighbours. Shimmering waves provoked by dummy wasps were recorded with
      high-resolution video cameras. Individual bees were identified by 3D-image
      analysis, and their strength of abdominal flipping was assessed by pixel-based
      luminance changes in sequential frames. For each agent, the directedness of wave
      propagation was based on wave direction, trigger direction, and the direction of
      the majority of shimmering-active neighbours. The data supported the bucket
      bridging hypothesis, but only for a small proportion of agents: linearity was
      confirmed for 2.5%, continuity for 11.3% and graduality for 0.4% of surface bees
      (but in 2.6% of those agents with high wave-strength levels). The complimentary
      part of 90% of surface bees did not conform to bucket bridging. This fuzziness is
      discussed in terms of self-organisation and evolutionary adaptedness in Giant
      honeybee colonies to respond to rapidly changing threats such as predatory wasps
      scanning in front of the nest.

PMID- 22662124
TI  - The influence of social comparison on visual representation of one's face.
AB  - Can the effects of social comparison extend beyond explicit evaluation to visual
      self-representation--a perceptual stimulus that is objectively verifiable,
      unambiguous, and frequently updated? We morphed images of participants' faces
      with attractive and unattractive references. With access to a mirror,
      participants selected the morphed image they perceived as depicting their face.
      Participants who engaged in upward comparison with relevant attractive targets
      selected a less attractive morph compared to participants exposed to control
      images (Study 1). After downward comparison with relevant unattractive targets
      compared to control images, participants selected a more attractive morph (Study
      2). Biased representations were not the products of cognitive accessibility of
      beauty constructs; comparisons did not influence representations of strangers'
      faces (Study 3). We discuss implications for vision, social comparison, and body
      image.

PMID- 22662125
TI  - Respiratory membrane endo-hydrogenase activity in the microaerophile Azorhizobium
      caulinodans is bidirectional.
AB  - BACKGROUND: The microaerophilic bacterium Azorhizobium caulinodans, when fixing
      N(2) both in pure cultures held at 20 uM dissolved O(2) tension and as
      endosymbiont of Sesbania rostrata legume nodules, employs a novel, respiratory
      membrane endo-hydrogenase to oxidize and recycle endogenous H(2) produced by
      soluble Mo-dinitrogenase activity at the expense of O(2). METHODS AND FINDINGS:
      From a bioinformatic analysis, this endo-hydrogenase is a core (6 subunit)
      version of (14 subunit) NADH:ubiquinone oxidoreductase (respiratory complex I).
      In pure A. caulinodans liquid cultures, when O(2) levels are lowered to <1 uM
      dissolved O(2) tension (true microaerobic physiology), in vivo endo-hydrogenase
      activity reverses and continuously evolves H(2) at high rates. In essence, H(+)
      ions then supplement scarce O(2) as respiratory-membrane electron acceptor.
      Paradoxically, from thermodynamic considerations, such hydrogenic respiratory
      membrane electron transfer need largely uncouple oxidative phosphorylation,
      required for growth of non-phototrophic aerobic bacteria, A. caulinodans
      included. CONCLUSIONS: A. caulinodans in vivo endo-hydrogenase catalytic activity
      is bidirectional. To our knowledge, this study is the first demonstration of
      hydrogenic respiratory-membrane electron transfer among aerobic (non
      fermentative) bacteria. When compared with O(2) tolerant hydrogenases in other
      organisms, A. caulinodans in vivo endo-hydrogenase mediated H(2) production rates
      (50,000 pmol 10(9).cells(-1) min(-1)) are at least one-thousandfold higher.
      Conceivably, A. caulinodans respiratory-membrane hydrogenesis might initiate H(2)
      crossfeeding among spatially organized bacterial populations whose individual
      cells adopt distinct metabolic states in response to variant O(2) availability.
      Such organized, physiologically heterogeneous cell populations might benefit from
      augmented energy transduction and growth rates of the populations, considered as
      a whole.

PMID- 22662126
TI  - Novel quinazolinone MJ-29 triggers endoplasmic reticulum stress and intrinsic
      apoptosis in murine leukemia WEHI-3 cells and inhibits leukemic mice.
AB  - The present study was to explore the biological responses of the newly compound,
      MJ-29 in murine myelomonocytic leukemia WEHI-3 cells in vitro and in vivo fates.
      We focused on the in vitro effects of MJ-29 on ER stress and mitochondria
      dependent apoptotic death in WEHI-3 cells, and to hypothesize that MJ-29 might
      fully impair the orthotopic leukemic mice. Our results indicated that a
      concentration-dependent decrease of cell viability was shown in MJ-29-treated
      cells. DNA content was examined utilizing flow cytometry, whereas apoptotic
      populations were determined using annexin V/PI, DAPI staining and TUNEL assay.
      Increasing vital factors of mitochondrial dysfunction by MJ-29 were further
      investigated. Thus, MJ-29-provaked apoptosis of WEHI-3 cells is mediated through
      the intrinsic pathway. Importantly, intracellular Ca(2+) release and ER stress
      associated signaling also contributed to MJ-29-triggered cell apoptosis. We found
      that MJ-29 stimulated the protein levels of calpain 1, CHOP and p-eIF2alpha
      pathways in WEHI-3 cells. In in vivo experiments, intraperitoneal administration
      of MJ-29 significantly improved the total survival rate, enhanced body weight and
      attenuated enlarged spleen and liver tissues in leukemic mice. The infiltration
      of immature myeloblastic cells into splenic red pulp was reduced in MJ-29-treated
      leukemic mice. Moreover, MJ-29 increased the differentiations of T and B cells
      but decreased that of macrophages and monocytes. Additionally, MJ-29-stimulated
      immune responses might be involved in anti-leukemic activity in vivo. Based on
      these observations, MJ-29 suppresses WEHI-3 cells in vitro and in vivo, and it is
      proposed that this potent and selective agent could be a new chemotherapeutic
      candidate for anti-leukemia in the future.

PMID- 22662128
TI  - GPUmotif: an ultra-fast and energy-efficient motif analysis program using
      graphics processing units.
AB  - Computational detection of TF binding patterns has become an indispensable tool
      in functional genomics research. With the rapid advance of new sequencing
      technologies, large amounts of protein-DNA interaction data have been produced.
      Analyzing this data can provide substantial insight into the mechanisms of
      transcriptional regulation. However, the massive amount of sequence data presents
      daunting challenges. In our previous work, we have developed a novel algorithm
      called Hybrid Motif Sampler (HMS) that enables more scalable and accurate motif
      analysis. Despite much improvement, HMS is still time-consuming due to the
      requirement to calculate matching probabilities position-by-position. Using the
      NVIDIA CUDA toolkit, we developed a graphics processing unit (GPU)-accelerated
      motif analysis program named GPUmotif. We proposed a "fragmentation" technique to
      hide data transfer time between memories. Performance comparison studies showed
      that commonly-used model-based motif scan and de novo motif finding procedures
      such as HMS can be dramatically accelerated when running GPUmotif on NVIDIA
      graphics cards. As a result, energy consumption can also be greatly reduced when
      running motif analysis using GPUmotif. The GPUmotif program is freely available
      at http://sourceforge.net/projects/gpumotif/

PMID- 22662127
TI  - Short-term long chain omega3 diet protects from neuroinflammatory processes and
      memory impairment in aged mice.
AB  - Regular consumption of food enriched in omega3 polyunsaturated fatty acids
      (omega3 PUFAs) has been shown to reduce risk of cognitive decline in elderly, and
      possibly development of Alzheimer's disease. Docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA) are the most likely active components of omega3-rich
      PUFAs diets in the brain. We therefore hypothesized that exposing mice to a DHA
      and EPA enriched diet may reduce neuroinflammation and protect against memory
      impairment in aged mice. For this purpose, mice were exposed to a control diet
      throughout life and were further submitted to a diet enriched in EPA and DHA
      during 2 additional months. Cytokine expression together with a thorough analysis
      of astrocytes morphology assessed by a 3D reconstruction was measured in the
      hippocampus of young (3-month-old) and aged (22-month-old) mice. In addition, the
      effects of EPA and DHA on spatial memory and associated Fos activation in the
      hippocampus were assessed. We showed that a 2-month EPA/DHA treatment increased
      these long-chain omega3 PUFAs in the brain, prevented cytokines expression and
      astrocytes morphology changes in the hippocampus and restored spatial memory
      deficits and Fos-associated activation in the hippocampus of aged mice.
      Collectively, these data indicated that diet-induced accumulation of EPA and DHA
      in the brain protects against neuroinflammation and cognitive impairment linked
      to aging, further reinforcing the idea that increased EPA and DHA intake may
      provide protection to the brain of aged subjects.

PMID- 22662129
TI  - Biophysical assessment of single cell cytotoxicity: diesel exhaust particle
      treated human aortic endothelial cells.
AB  - Exposure to diesel exhaust particles (DEPs), a major source of traffic-related
      air pollution, has become a serious health concern due to its adverse influences
      on human health including cardiovascular and respiratory disorders. To elucidate
      the relationship between biophysical properties (cell topography, cytoskeleton
      organizations, and cell mechanics) and functions of endothelial cells exposed to
      DEPs, atomic force microscope (AFM) was applied to analyze the toxic effects of
      DEPs on a model cell line from human aortic endothelial cells (HAECs).
      Fluorescence microscopy and flow cytometry were also applied to further explore
      DEP-induced cytotoxicity in HAECs. Results revealed that DEPs could negatively
      impair cell viability and alter membrane nanostructures and cytoskeleton
      components in a dosage- and a time-dependent manner; and analyses suggested that
      DEPs-induced hyperpolarization in HAECs appeared in a time-dependent manner,
      implying DEP treatment would lead to vasodilation, which could be supported by
      down-regulation of cell biophysical properties (e.g., cell elasticity). These
      findings are consistent with the conclusion that DEP exposure triggers important
      biochemical and biophysical changes that would negatively impact the pathological
      development of cardiovascular diseases. For example, DEP intervention would be
      one cause of vasodilation, which will expand understanding of biophysical aspects
      associated with DEP cytotoxicity in HAECs.

PMID- 22662131
TI  - Evaluation of a rapid dipstick (Crystal VC) for the diagnosis of cholera in
      Zanzibar and a comparison with previous studies.
AB  - BACKGROUND: The gold standard for the diagnosis of cholera is stool culture, but
      this requires laboratory facilities and takes at least 24 hours. A rapid
      diagnostic test (RDT) that can be used by minimally trained staff at treatment
      centers could potentially improve the reporting and management of cholera
      outbreaks. METHODS: We evaluated the Crystal VCTM RDT under field conditions in
      Zanzibar in 2009. Patients presenting to treatment centers with watery diarrhea
      provided a stool sample for rapid diagnostic testing. Results were compared to
      stool culture performed in a reference laboratory. We assessed the overall
      performance of the RDT and evaluated whether previous intake of antibiotics,
      intravenous fluids, location of testing, and skill level of the technician
      affected the RDT results. RESULTS: We included stool samples from 624 patients.
      Compared to culture, the overall sensitivity of the RDT was 93.1% (95%CI: 88.7 to
      96.2%), specificity was 49.2% (95%CI: 44.3 to 54.1%), the positive predictive
      value was 47.0% (95%CI: 42.1 to 52.0%) and the negative predictive value was
      93.6% (95%CI: 89.6 to 96.5%). The overall false positivity rate was 50.8%
      (213/419); fieldworkers frequently misread very faint test lines as positive.
      CONCLUSION: The observed sensitivity of the Crystal VC RDT evaluated was similar
      compared to earlier versions, while specificity was poorer. The current version
      of the RDT could potentially be used as a screening tool in the field. Because of
      the high proportion of false positive results when field workers test stool
      specimens, positive results will need to be confirmed with stool culture.

PMID- 22662130
TI  - Using prior information from the medical literature in GWAS of oral cancer
      identifies novel susceptibility variant on chromosome 4--the AdAPT method.
AB  - BACKGROUND: Genome-wide association studies (GWAS) require large sample sizes to
      obtain adequate statistical power, but it may be possible to increase the power
      by incorporating complementary data. In this study we investigated the
      feasibility of automatically retrieving information from the medical literature
      and leveraging this information in GWAS. METHODS: We developed a method that
      searches through PubMed abstracts for pre-assigned keywords and key concepts, and
      uses this information to assign prior probabilities of association for each
      single nucleotide polymorphism (SNP) with the phenotype of interest--the
      Adjusting Association Priors with Text (AdAPT) method. Association results from a
      GWAS can subsequently be ranked in the context of these priors using the Bayes
      False Discovery Probability (BFDP) framework. We initially tested AdAPT by
      comparing rankings of known susceptibility alleles in a previous lung cancer
      GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. RESULTS:
      Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT
      BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top
      five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene
      region of 4q23, displayed a statistically significant association with oral
      cancer risk in the replication phase (per-rare-allele log additive p-value
      [p(trend)] = 2.5*10(-3)). The combined OR for having one additional rare allele
      was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously
      identified susceptibility SNPs that are associated with overall UADT cancer in
      this gene region. We also investigated if rs991316 was associated with other
      cancers of the upper aerodigestive tract (UADT), but no additional association
      signal was found. CONCLUSION: This study highlights the potential utility of
      systematically incorporating prior knowledge from the medical literature in
      genome-wide analyses using the AdAPT methodology. AdAPT is available online (url:
      http://services.gate.ac.uk/lld/gwas/service/config).

PMID- 22662132
TI  - Topical insulin accelerates wound healing in diabetes by enhancing the AKT and
      ERK pathways: a double-blind placebo-controlled clinical trial.
AB  - BACKGROUND: Wound healing is impaired in diabetes mellitus, but the mechanisms
      involved in this process are virtually unknown. Proteins belonging to the insulin
      signaling pathway respond to insulin in the skin of rats. OBJECTIVE: The purpose
      of this study was to investigate the regulation of the insulin signaling pathway
      in wound healing and skin repair of normal and diabetic rats, and, in parallel,
      the effect of a topical insulin cream on wound healing and on the activation of
      this pathway. RESEARCH DESIGN AND METHODS: We investigated insulin signaling by
      immunoblotting during wound healing of control and diabetic animals with or
      without topical insulin. Diabetic patients with ulcers were randomized to receive
      topical insulin or placebo in a prospective, double-blind and placebo-controlled,
      randomized clinical trial (NCT 01295177) of wound healing. RESULTS AND
      CONCLUSIONS: Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in
      the tissue of healing wounds compared to intact skin, suggesting that the insulin
      signaling pathway may have an important role in this process. These pathways were
      attenuated in the wounded skin of diabetic rats, in parallel with an increase in
      the time of complete wound healing. Upon topical application of insulin cream,
      the wound healing time of diabetic animals was normalized, followed by a reversal
      of defective insulin signal transduction. In addition, the treatment also
      increased expression of other proteins, such as eNOS (also in bone marrow), VEGF,
      and SDF-1alpha in wounded skin. In diabetic patients, topical insulin cream
      markedly improved wound healing, representing an attractive and cost-free method
      for treating this devastating complication of diabetes. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01295177.

PMID- 22662133
TI  - Inferring phenotypic properties from single-cell characteristics.
AB  - Flow cytometry provides multi-dimensional data at the single-cell level. Such
      data contain information about the cellular heterogeneity of bulk samples, making
      it possible to correlate single-cell features with phenotypic properties of bulk
      tissues. Predicting phenotypes from single-cell measurements is a difficult
      challenge that has not been extensively studied. The 6th Dialogue for Reverse
      Engineering Assessments and Methods (DREAM6) invited the research community to
      develop solutions to a computational challenge: classifying acute myeloid
      leukemia (AML) positive patients and healthy donors using flow cytometry data.
      DREAM6 provided flow cytometry data for 359 normal and AML samples, and the class
      labels for half of the samples. Researchers were asked to predict the class
      labels of the remaining half. This paper describes one solution that was
      constructed by combining three algorithms: spanning-tree progression analysis of
      density-normalized events (SPADE), earth mover's distance, and a nearest-neighbor
      classifier called Relief. This solution was among the top-performing methods that
      achieved 100% prediction accuracy.

PMID- 22662134
TI  - Influence of prenatal arsenic exposure and newborn sex on global methylation of
      cord blood DNA.
AB  - BACKGROUND: An emerging body of evidence indicates that early-life arsenic (As)
      exposure may influence the trajectory of health outcomes later in life. However,
      the mechanisms underlying these observations are unknown. OBJECTIVE: The
      objective of this study was to investigate the influence of prenatal As exposure
      on global methylation of cord blood DNA in a study of mother/newborn pairs in
      Matlab, Bangladesh. DESIGN: Maternal and cord blood DNA were available from a
      convenience sample of 101 mother/newborn pairs. Measures of As exposure included
      maternal urinary As (uAs), maternal blood As (mbAs) and cord blood As (cbAs).
      Several measures of global DNA methylation were assessed, including the [3H]
      methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA.
      RESULTS: In the total sample, increasing quartiles of maternal uAs were
      associated with an increase in covariate-adjusted means of newborn global DNA
      methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1)
      and Q2 vs. Q4; p = 0.06 and 0.04, respectively). Sex-specific linear regression
      analyses, while not reaching significance level of 0.05, indicated that the
      associations between As exposures and Alu, LINE-1 and LUMA were positive among
      male newborns (N = 58) but negative among female newborns (N = 43); tests for sex
      differences were borderline significant for the association of cbAs and mbAs with
      Alu (p = 0.05 and 0.09, respectively) and for the association between maternal
      uAs and LINE-1 (p = 0.07). Sex-specific correlations between maternal urinary
      creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident
      (p<0.05). CONCLUSIONS: These results suggest that prenatal As exposure is
      associated with global DNA methylation in cord blood DNA, possibly in a sex
      specific manner. Arsenic-induced epigenetic modifications in utero may
      potentially influence disease outcomes later in life. Additional studies are
      needed to confirm these findings and to examine the persistence of DNA
      methylation marks over time.

PMID- 22662135
TI  - Optimising strategies for Plasmodium falciparum malaria elimination in Cambodia:
      primaquine, mass drug administration and artemisinin resistance.
AB  - BACKGROUND: Malaria elimination requires a variety of approaches individually
      optimized for different transmission settings. A recent field study in an area of
      low seasonal transmission in South West Cambodia demonstrated dramatic reductions
      in malaria parasite prevalence following both mass drug administration (MDA) and
      high treatment coverage of symptomatic patients with artemisinin-piperaquine plus
      primaquine. This study employed multiple combined strategies and it was unclear
      what contribution each made to the reductions in malaria. METHOD AND FINDINGS: A
      mathematical model fitted to the trial results was used to assess the effects of
      the various components of these interventions, design optimal elimination
      strategies, and explore their interactions with artemisinin resistance, which has
      recently been discovered in Western Cambodia. The modelling indicated that most
      of the initial reduction of P. falciparum malaria resulted from MDA with
      artemisinin-piperaquine. The subsequent continued decline and near elimination
      resulted mainly from high coverage with artemisinin-piperaquine treatment. Both
      these strategies were more effective with the addition of primaquine. MDA with
      artemisinin combination therapy (ACT) increased the proportion of artemisinin
      resistant infections, although much less than treatment of symptomatic cases with
      ACT, and this increase was slowed by adding primaquine. Artemisinin resistance
      reduced the effectiveness of interventions using ACT when the prevalence of
      resistance was very high. The main results were robust to assumptions about
      primaquine action, and immunity. CONCLUSIONS: The key messages of these modelling
      results for policy makers were: high coverage with ACT treatment can produce a
      long-term reduction in malaria whereas the impact of MDA is generally only short
      term; primaquine enhances the effect of ACT in eliminating malaria and reduces
      the increase in proportion of artemisinin resistant infections; parasite
      prevalence is a better surveillance measure for elimination programmes than
      numbers of symptomatic cases; combinations of interventions are most effective
      and sustained efforts are crucial for successful elimination.

PMID- 22662136
TI  - Spatial and temporal dynamics of hepatitis B virus D genotype in Europe and the
      Mediterranean Basin.
AB  - Hepatitis B virus genotype D can be found in many parts of the world and is the
      most prevalent strain in south-eastern Europe, the Mediterranean Basin, the
      Middle East, and the Indian sub-continent. The epidemiological history of the D
      genotype and its subgenotypes is still obscure because of the scarcity of
      appropriate studies. We retrieved from public databases a total of 312 gene P
      sequences of HBV genotype D isolated in various countries throughout the world,
      and reconstructed the spatio-temporal evolutionary dynamics of the HBV-D epidemic
      using a bayesian framework.The phylogeographical analysis showed that India had
      the highest posterior probability of being the location of the tree root, whereas
      central Asia was the most probable location of the common ancestor of
      subgenotypes D1-D3. HBV-D5 (identified in native Indian populations) diverged
      from the tree root earlier than D1-D3. The time of the most recent common
      ancestor (tMRCA) of the tree root was 128 years ago, which suggests that the
      common ancestor of the currently circulating subgenotypes existed in the second
      half of the XIX century. The mean tMRCA of subgenotypes D1-D3 was between the
      1940s and the 1950-60s. On the basis of our phylogeographic reconstruction, it
      seems that HBV-D reached the Mediterranean area in the middle of the XX century
      by means of at least two routes: the first pathway (mainly due to the spread of
      subgenotype D1) crossing the Middle East and reaching north Africa and the
      eastern Mediterranean, and the second pathway (closely associated with D2) that
      crossed the former Soviet Union and reached eastern Europe and the Mediterranean
      through Albania. We hypothesise that the main route of dispersion of genotype D
      was the unsafe use of injections and drug addiction.

PMID- 22662137
TI  - Retrospective study of the incidence of HFMD and seroepidemiology of antibodies
      against EV71 and CoxA16 in prenatal women and their infants.
AB  - BACKGROUND: Hand, foot, and mouth disease (HFMD) has been emerging as an
      important public problem over the past few decades, especially in Asian and
      Pacific regions. A national program on EV71 vaccine development against HFMD was
      initiated in China, in 2008, which called for a need for seroepidemiological
      study for the target population. METHODOLOGY/PRINCIPAL FINDINGS: This was a
      retrospective study conducted in Jiangsu Province, in October, 2010. We measured
      the neutralizing antibodies against EV71 and CoxA16 in a cohort of infants aged
      of 2, 7, 12, and 27-38 months and their mothers just before delivery. Series sera
      samples from 975 infants and 555 mothers were collected and analyzed.
      Questionnaires on the history of HFMD were completed in the survey. A total of
      143 HFMD cases were collected, but only 11.2% were reported to the National
      Infectious Disease Information Management System. The level of maternal antibody
      titers decreased dramatically during the first 7 month and remained at a
      relatively low level thereafter. But it increased significantly from month 12 to
      months 27-38. The accumulate incidence density of HFMD demonstrated a significant
      increase after 14 months of age, resulting in a accumulate incidence density of
      50.8/1000 person-years in survey period. Seropositivity of EV71 antibody in
      infants at the age of 2 months seems to demonstrate a protective effect against
      HFMD. CONCLUSIONS AND SIGNIFICANCE: High seropositive rate of EV71 and CoxA16
      antibody was found in prenatal women in mainland China, and there is a need to
      enhance the HFMD case management and the current surveillance system. We suggest
      that infants aged between 6 to 14 months should have the first priority to
      receive EV71 vaccine.

PMID- 22662138
TI  - A stochastic description of Dictyostelium chemotaxis.
AB  - Chemotaxis, the directed motion of a cell toward a chemical source, plays a key
      role in many essential biological processes. Here, we derive a statistical model
      that quantitatively describes the chemotactic motion of eukaryotic cells in a
      chemical gradient. Our model is based on observations of the chemotactic motion
      of the social ameba Dictyostelium discoideum, a model organism for eukaryotic
      chemotaxis. A large number of cell trajectories in stationary, linear
      chemoattractant gradients is measured, using microfluidic tools in combination
      with automated cell tracking. We describe the directional motion as the interplay
      between deterministic and stochastic contributions based on a Langevin equation.
      The functional form of this equation is directly extracted from experimental data
      by angle-resolved conditional averages. It contains quadratic deterministic
      damping and multiplicative noise. In the presence of an external gradient, the
      deterministic part shows a clear angular dependence that takes the form of a
      force pointing in gradient direction. With increasing gradient steepness, this
      force passes through a maximum that coincides with maxima in both speed and
      directionality of the cells. The stochastic part, on the other hand, does not
      depend on the orientation of the directional cue and remains independent of the
      gradient magnitude. Numerical simulations of our probabilistic model yield
      quantitative agreement with the experimental distribution functions. Thus our
      model captures well the dynamics of chemotactic cells and can serve to quantify
      differences and similarities of different chemotactic eukaryotes. Finally, on the
      basis of our model, we can characterize the heterogeneity within a population of
      chemotactic cells.

PMID- 22662139
TI  - Monogeneans of West African cichlid fish: evolution and cophylogenetic
      interactions.
AB  - The goals of this paper were to investigate phylogenetic and evolutionary
      patterns of cichlid fish from West Africa and their Cichlidogyrus and Scutogyrus
      monogenean parasites, to uncover the presence of host-parasite cospeciation and
      to assess the level of morphological adaptation in parasites. This required the
      following steps, each one representing specific objectives of this paper: (1) to
      build phylogenetic trees for Cichlidogyrus and Scutogyrus species based on
      ribosomal DNA sequences, (2) to investigate phylogenetic relationships within
      West African cichlid fish based on the analysis of mitochondrial cytochrome b DNA
      sequences, (3) to investigate host-parasite cophylogenetic history to gain clues
      on parasite speciation process, and (4) to investigate the link between the
      morphology of the attachment apparatus and parasite phylogeny. Phylogenetic
      analyses supported the monophyletic origin of the Cichlidogyrus/Scutogyrus group,
      and suggested that Cichlidogyrus is polyphyletic and that Scutogyrus is
      monophyletic. The phylogeny of Cichlidae supported the separation of
      mouthbrooders and substrate-brooders and is consistent with the hypothesis that
      the mouthbrooding behavior of Oreochromis and Sarotherodon evolved from substrate
      brooding behavior. The mapping of morphological characters of the haptor onto the
      parasite phylogenetic tree suggests that the attachment organ has evolved from a
      very simple form to a more complex one. The cophylogenetic analyses indicated a
      significant fit between trees using distance-based tests, but no significant
      cospeciation signal using tree-based tests, suggesting the presence of parasite
      duplications and host switches on related host species. This shed some light on
      the diversification process of Cichlidogyrus species parasitizing West African
      cichlids.

PMID- 22662140
TI  - Genome-wide study of the defective sucrose fermenter strain of Vibrio cholerae
      from the Latin American cholera epidemic.
AB  - The 7th cholera pandemic reached Latin America in 1991, spreading from Peru to
      virtually all Latin American countries. During the late epidemic period, a strain
      that failed to ferment sucrose dominated cholera outbreaks in the Northern
      Brazilian Amazon region. In order to understand the genomic characteristics and
      the determinants of this altered sucrose fermenting phenotype, the genome of the
      strain IEC224 was sequenced. This paper reports a broad genomic study of this
      strain, showing its correlation with the major epidemic lineage. The potentially
      mobile genomic regions are shown to possess GC content deviation, and harbor the
      main V. cholera virulence genes. A novel bioinformatic approach was applied in
      order to identify the putative functions of hypothetical proteins, and was
      compared with the automatic annotation by RAST. The genome of a large
      bacteriophage was found to be integrated to the IEC224's alanine aminopeptidase
      gene. The presence of this phage is shown to be a common characteristic of the El
      Tor strains from the Latin American epidemic, as well as its putative ancestor
      from Angola. The defective sucrose fermenting phenotype is shown to be due to a
      single nucleotide insertion in the V. cholerae sucrose-specific transportation
      gene. This frame-shift mutation truncated a membrane protein, altering its
      structural pore-like conformation. Further, the identification of a common
      bacteriophage reinforces both the monophyletic and African-Origin hypotheses for
      the main causative agent of the 1991 Latin America cholera epidemics.

PMID- 22662142
TI  - Synthesis of the tetrasaccharide motif and its structural analog corresponding to
      the lipopolysaccharide of Escherichia coli O75.
AB  - BACKGROUND: Extraintestinal pathogenic E. coli are mostly responsible for a
      diverse spectrum of invasive human and animal infections leading to the urinary
      tract infections. Bacterial lipopolysaccharides are responsible for their
      pathogenicity and their interactions with host immune responses. In spite of
      several breakthroughs in the development of therapeutics to combat urinary tract
      infections and related diseases, the emergence of multidrug-resistant bacterial
      strains is a serious concern. Lipopolysaccharides are attractive targets for the
      development of long-term therapeutic agents to eradicate the infections. Since
      the natural sources cannot provide the required amount of oligosaccharides,
      development of chemical synthetic strategies for their synthesis is relevant to
      gain access to a reservoir of oligosaccharides and their close analogs.
      METHODOLOGY: Two tetrasaccharide derivatives were synthesized from a single
      disaccharide intermediate. beta-D-mannoside moiety was prepared from beta-D
      glucoside moiety following oxidation-reduction methodology. A [2+2]
      stereoselective block glycosylation strategy has been adopted for the preparation
      of tetrasaccharide derivative. alpha-D-glucosamine moiety was prepared from alpha
      D-mannosidic moiety following triflate formation at C-2 and S(N)(2) substitution.
      A one-pot iterative glycosylation exploiting the orthogonal property of
      thioglycoside was carried out during the synthesis of tetrasaccharide analog.
      RESULTS: Synthesis of the tetrasaccharide motif (1) and its structural analog (2)
      corresponding to the lipopolysaccharide of Escherichia coli O75 was successfully
      achieved in excellent yield. Most of the reactions are clean and high yielding.
      Both compounds 1 and 2 were synthesized as their 4-methoxyphenyl glycoside, which
      can act as a temporary anomeric protecting group for further use of these
      tetrasaccharides in the preparation of glycoconjugates.

PMID- 22662141
TI  - Chemical PARP inhibition enhances growth of Arabidopsis and reduces anthocyanin
      accumulation and the activation of stress protective mechanisms.
AB  - Poly-ADP-ribose polymerase (PARP) post-translationally modifies proteins through
      the addition of ADP-ribose polymers, yet its role in modulating plant development
      and stress responses is only poorly understood. The experiments presented here
      address some of the gaps in our understanding of its role in stress tolerance and
      thereby provide new insights into tolerance mechanisms and growth. Using a
      combination of chemical and genetic approaches, this study characterized
      phenotypes associated with PARP inhibition at the physiological level. Molecular
      analyses including gene expression analysis, measurement of primary metabolites
      and redox metabolites were used to understand the underlying processes. The
      analysis revealed that PARP inhibition represses anthocyanin and ascorbate
      accumulation under stress conditions. The reduction in defense is correlated with
      enhanced biomass production. Even in unstressed conditions protective genes and
      molecules are repressed by PARP inhibition. The reduced anthocyanin production
      was shown to be based on the repression of transcription of key regulatory and
      biosynthesis genes. PARP is a key factor for understanding growth and stress
      responses of plants. PARP inhibition allows plants to reduce protection such as
      anthocyanin, ascorbate or Non-Photochemical-Quenching whilst maintaining high
      energy levels likely enabling the observed enhancement of biomass production
      under stress, opening interesting perspectives for increasing crop productivity.

PMID- 22662143
TI  - Statistical analysis of the processes controlling choline and ethanolamine
      glycerophospholipid molecular species composition.
AB  - The regulation and maintenance of the cellular lipidome through biosynthetic,
      remodeling, and catabolic mechanisms are critical for biological homeostasis
      during development, health and disease. These complex mechanisms control the
      architectures of lipid molecular species, which have diverse yet highly regulated
      fatty acid chains at both the sn1 and sn2 positions. Phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE) serve as the predominant biophysical scaffolds in
      membranes, acting as reservoirs for potent lipid signals and regulating numerous
      enzymatic processes. Here we report the first rigorous computational dissection
      of the mechanisms influencing PC and PE molecular architectures from high
      throughput shotgun lipidomic data. Using novel statistical approaches, we have
      analyzed multidimensional mass spectrometry-based shotgun lipidomic data from
      developmental mouse heart and mature mouse heart, lung, brain, and liver tissues.
      We show that in PC and PE, sn1 and sn2 positions are largely independent, though
      for low abundance species regulatory processes may interact with both the sn1 and
      sn2 chain simultaneously, leading to cooperative effects. Chains with similar
      biochemical properties appear to be remodeled similarly. We also see that sn2
      positions are more regulated than sn1, and that PC exhibits stronger cooperative
      effects than PE. A key aspect of our work is a novel statistically rigorous
      approach to determine cooperativity based on a modified Fisher's exact test using
      Markov Chain Monte Carlo sampling. This computational approach provides a novel
      tool for developing mechanistic insight into lipidomic regulation.

PMID- 22662144
TI  - Reduced cortisol and metabolic responses of thin ewes to an acute cold challenge
      in mid-pregnancy: implications for animal physiology and welfare.
AB  - BACKGROUND: Low food availability leading to reductions in Body Condition Score
      (BCS; 0 indicates emaciation and 5 obesity) in sheep often coincides with low
      temperatures associated with the onset of winter in New Zealand. The ability to
      adapt to reductions in environmental temperature may be impaired in animals with
      low BCS, in particular during pregnancy when metabolic demand is higher. Here we
      assess whether BCS affects a pregnant animal's ability to cope with cold
      challenges. METHODS: Eighteen pregnant ewes with a BCS of 2.7+/-0.1 were fed to
      attain low (LBC: BCS2.3+/-0.1), medium (MBC: BCS3.2+/-0.2) or high BCS (HBC:
      BCS3.6+/-0.2). Shorn ewes were exposed to a 6-h acute cold challenge in a climate
      controlled room (wet and windy conditions, 4.4+/-0.1 degrees C) in mid-pregnancy.
      Blood samples were collected during the BCS change phase, acute cold challenge
      and recovery phase. RESULTS: During the BCS change phase, plasma glucose and
      leptin concentrations declined while free fatty acids (FFA) increased in LBC
      compared to MBC (P<0.01, P<0.01 and P<0.05, respectively) and HBC ewes (P<0.05,
      P<0.01 and P<0.01, respectively). During the cold challenge, plasma cortisol
      concentrations were lower in LBC than MBC (P<0.05) and HBC ewes (P<0.05), and FFA
      and insulin concentrations were lower in LBC than HBC ewes (P<0.05 and P<0.001,
      respectively). Leptin concentrations declined in MBC and HBC ewes while remaining
      unchanged in LBC ewes (P<0.01). Glucose concentrations and internal body
      temperature (T(core)) increased in all treatments, although peak T(core) tended
      to be higher in HBC ewes (P<0.1). During the recovery phase, T4 concentrations
      were lower in LBC ewes (P<0.05). CONCLUSION: Even though all ewes were able to
      increase T(core) and mobilize glucose, low BCS animals had considerably reduced
      cortisol and metabolic responses to a cold challenge in mid-pregnancy, suggesting
      that their ability to adapt to cold challenges through some of the expected
      pathways was reduced.

PMID- 22662145
TI  - Ensemble analysis of angiogenic growth in three-dimensional microfluidic cell
      cultures.
AB  - We demonstrate ensemble three-dimensional cell cultures and quantitative analysis
      of angiogenic growth from uniform endothelial monolayers. Our approach combines
      two key elements: a micro-fluidic assay that enables parallelized angiogenic
      growth instances subject to common extracellular conditions, and an automated
      image acquisition and processing scheme enabling high-throughput, unbiased
      quantification of angiogenic growth. Because of the increased throughput of the
      assay in comparison to existing three-dimensional morphogenic assays, statistical
      properties of angiogenic growth can be reliably estimated. We used the assay to
      evaluate the combined effects of vascular endothelial growth factor (VEGF) and
      the signaling lipid sphingoshine-1-phosphate (S1P). Our results show the
      importance of S1P in amplifying the angiogenic response in the presence of VEGF
      gradients. Furthermore, the application of S1P with VEGF gradients resulted in
      angiogenic sprouts with higher aspect ratio than S1P with background levels of
      VEGF, despite reduced total migratory activity. This implies a synergistic effect
      between the growth factors in promoting angiogenic activity. Finally, the
      variance in the computed angiogenic metrics (as measured by ensemble standard
      deviation) was found to increase linearly with the ensemble mean. This finding is
      consistent with stochastic agent-based mathematical models of angiogenesis that
      represent angiogenic growth as a series of independent stochastic cell-level
      decisions.

PMID- 22662146
TI  - Lutzomyia umbratilis, the main vector of Leishmania guyanensis, represents a
      novel species complex?
AB  - BACKGROUND: Lutzomyia umbratilis is an important Leishmania guyanensis vector in
      South America. Previous studies have suggested differences in the vector
      competence between L. umbratilis populations situated on opposite banks of the
      Amazonas and Negro Rivers in the central Amazonian Brazil region, likely
      indicating a species complex. However, few studies have been performed on these
      populations and the taxonomic status of L. umbratilis remains unclear.
      METHODOLOGY/PRINCIPAL FINDINGS: Phylogeographic structure was estimated for six
      L. umbratilis samples from the central Amazonian region in Brazil by analyzing
      mtDNA using 1181 bp of the COI gene to assess whether the populations on opposite
      banks of these rivers consist of incipient or distinct species. The genetic
      diversity was fairly high and the results revealed two distinct clades ( =
      lineages) with 1% sequence divergence. Clade I consisted of four samples from the
      left bank of the Amazonas and Negro Rivers, whereas clade II comprised two
      samples from the right bank of Negro River. No haplotypes were shared between
      samples of two clades. Samples within clades exhibited low to moderate genetic
      differentiation (F(ST) = -0.0390-0.1841), whereas samples between clades
      exhibited very high differentiation (F(ST) = 0.7100-0.8497) and fixed
      differences. These lineages have diverged approximately 0.22 Mya in the middle
      Pleistocene. Demographic expansion was detected for the lineages I and II
      approximately 30,448 and 15,859 years ago, respectively, in the late Pleistocene.
      CONCLUSIONS/SIGNIFICANCE: The two genetic lineages may represent an advanced
      speciation stage suggestive of incipient or distinct species within L.
      umbratilis. These findings suggest that the Amazonas and Negro Rivers may be
      acting as effective barriers, thus preventing gene flow between populations on
      opposite sides. Such findings have important implications for epidemiological
      studies, especially those related to vector competence and anthropophily, and for
      vector control strategies. In addition, L. umbratilis represents an interesting
      example in speciation studies.

PMID- 22662147
TI  - Evolution of eye morphology and rhodopsin expression in the Drosophila
      melanogaster species subgroup.
AB  - A striking diversity of compound eye size and shape has evolved among insects.
      The number of ommatidia and their size are major determinants of the visual
      sensitivity and acuity of the compound eye. Each ommatidium is composed of eight
      photoreceptor cells that facilitate the discrimination of different colours via
      the expression of various light sensitive Rhodopsin proteins. It follows that
      variation in eye size, shape, and opsin composition is likely to directly
      influence vision. We analyzed variation in these three traits in D. melanogaster,
      D. simulans and D. mauritiana. We show that D. mauritiana generally has larger
      eyes than its sibling species, which is due to a combination of larger ommatidia
      and more ommatidia. In addition, intra- and inter-specific differences in eye
      size among D. simulans and D. melanogaster strains are mainly caused by variation
      in ommatidia number. By applying a geometric morphometrics approach to assess
      whether the formation of larger eyes influences other parts of the head capsule,
      we found that an increase in eye size is associated with a reduction in the
      adjacent face cuticle. Our shape analysis also demonstrates that D. mauritiana
      eyes are specifically enlarged in the dorsal region. Intriguingly, this dorsal
      enlargement is associated with enhanced expression of rhodopsin 3 in D.
      mauritiana. In summary, our data suggests that the morphology and functional
      properties of the compound eyes vary considerably within and among these closely
      related Drosophila species and may be part of coordinated morphological changes
      affecting the head capsule.

PMID- 22662148
TI  - Relative effectiveness of mating success and sperm competition at eliminating
      deleterious mutations in Drosophila melanogaster.
AB  - Condition-dependence theory predicts that sexual selection will facilitate
      adaptation by selecting against deleterious mutations that affect the expression
      of sexually selected traits indirectly via condition. Recent empirical studies
      have provided support for this prediction; however, their results do not
      elucidate the relative effects of pre- and postcopulatory sexual selection on
      deleterious mutations. We used the Drosophila melanogaster model system to
      discern the relative contributions of pre- and postcopulatory processes to
      selection against deleterious mutations. To assess second-male ejaculate
      competition success (P2; measured as the proportion of offspring attributable to
      the experimental male) and mating success, mutant and wild-type male D.
      melanogaster were given the opportunity to mate with females that were previously
      mated to a standard competitor male. This process was repeated for males
      subjected to a diet quality manipulation to test for effects of environmentally
      manipulated condition on P2 and mating success. While none of the tested
      mutations affected P2, there was a clear effect of condition. Conversely, several
      of the mutations affected mating success, while condition showed no effect. Our
      results suggest that precopulatory selection may be more effective than
      postcopulatory selection at removing deleterious mutations. The opposite result
      obtained for our diet manipulation points to an interesting discrepancy between
      environmental and genetic manipulations of condition, which may be explained by
      the multidimensionality of condition. Establishing whether the various stages of
      sexual selection affect deleterious mutations differently, and to what extent,
      remains an important issue to resolve.

PMID- 22662149
TI  - The effect of stimulus duration and motor response in hemispatial neglect during
      a visual search task.
AB  - Patients with hemispatial neglect exhibit a myriad of profound deficits. A
      hallmark of this syndrome is the patients' absence of awareness of items located
      in their contralesional space. Many studies, however, have demonstrated that
      neglect patients exhibit some level of processing of these neglected items. It
      has been suggested that unconscious processing of neglected information may
      manifest as a fast denial. This theory of fast denial proposes that neglected
      stimuli are detected in the same way as non-neglected stimuli, but without overt
      awareness. We evaluated the fast denial theory by conducting two separate visual
      search task experiments, each differing by the duration of stimulus presentation.
      Specifically, in Experiment 1 each stimulus remained in the participants' visual
      field until a response was made. In Experiment 2 each stimulus was presented for
      only a brief duration. We further evaluated the fast denial theory by comparing
      verbal to motor task responses in each experiment. Overall, our results from both
      experiments and tasks showed no evidence for the presence of implicit knowledge
      of neglected stimuli. Instead, patients with neglect responded the same when they
      neglected stimuli as when they correctly reported stimulus absence. These
      findings thus cast doubt on the concept of the fast denial theory and its
      consequent implications for non-conscious processing. Importantly, our study
      demonstrated that the only behavior affected was during conscious detection of
      ipsilesional stimuli. Specifically, patients were slower to detect stimuli in
      Experiment 1 compared to Experiment 2, suggesting a duration effect occurred
      during conscious processing of information. Additionally, reaction time and
      accuracy were similar when reporting verbally versus motorically. These results
      provide new insights into the perceptual deficits associated with neglect and
      further support other work that falsifies the fast denial account of non
      conscious processing in hemispatial visual neglect.

PMID- 22662150
TI  - How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA
      study of the Swiss Working Group of Breast- and Gynecopathologists.
AB  - Adjuvant chemotherapy decisions in breast cancer are increasingly based on the
      pathologist's assessment of tumor proliferation. The Swiss Working Group of
      Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency
      of Ki-67-based proliferative fraction in breast carcinomas. METHODS: Five
      pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1,
      G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over
      Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or
      pre-defined areas of the tumors, comparing centrally immunostained slides with
      slides immunostained in the different laboratoires. To study intra-observer
      variability, the same tumors were re-examined 4 months later. RESULTS: The Kappa
      values for the first series of ten carcinomas of various degrees of
      differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56
      0.72). However, we found very high inter-observer variabilities (Kappa 0.04-0.14)
      in the read-outs of the G2 carcinomas. It was not possible to explain the
      inconsistencies exclusively by any of the following factors: (i) pathologists'
      divergent definitions of what counts as a positive nucleus (ii) the mode of
      assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv)
      the selection of the tumor area in which to count. Despite intensive
      confrontation of all participating pathologists with the problem, inter-observer
      agreement did not improve when the same slides were re-examined 4 months later
      (Kappa 0.01-0.04) and intra-observer agreement was likewise poor (Kappa 0.00
      0.35). CONCLUSION: Assessment of mid-range Ki-67-LI suffers from high inter- and
      intra-observer variability. Oncologists should be aware of this caveat when using
      Ki-67-LI as a basis for treatment decisions in moderately differentiated breast
      carcinomas.

PMID- 22662151
TI  - Validating the German version of the Quality of Relationship Inventory:
      confirming the three-factor structure and report of psychometric properties.
AB  - Research on psychosocial influences such as relationship characteristics has
      received increased attention in the clinical as well as social-psychological
      field. Several studies demonstrated that the quality of relationships, in
      particular with respect to the perceived support within intimate relationships,
      profoundly affects individuals' mental and physical health. There is, however, a
      limited choice of valid and internationally known assessments of relationship
      quality in Germany. We report the validation of the German version of the Quality
      of Relationships Inventory (QRI). First, we evaluated its factor structure in a
      representative German sample of 1.494 participants by means of confirmatory
      factor analysis. Our findings support the previously proposed three-factor
      structure. Second, importance and satisfaction with different relationship
      domains (family/children and relationship/sexuality) were linked with the QRI
      scales, demonstrating high construct validity. Finally, we report sex and age
      differences regarding the perceived relationship support, conflict and depth in
      our German sample. In conclusion, the QRI is a reliable and valid measurement to
      assess social support in romantic relationships in the German population.

PMID- 22662152
TI  - Selective impairments of resting-state networks in minimal hepatic
      encephalopathy.
AB  - BACKGROUND: Minimal hepatic encephalopathy (MHE) is a neuro-cognitive dysfunction
      characterized by impairment in attention, vigilance and integrative functions,
      while the sensorimotor function was often unaffected. Little is known, so far,
      about the exact neuro-pathophysiological mechanisms of aberrant cognition
      function in this disease. METHODOLOGY/PRINCIPAL FINDINGS: To investigate how the
      brain function is changed in MHE, we applied a resting-state fMRI approach with
      independent component analysis (ICA) to assess the differences of resting-state
      networks (RSNs) between MHE patients and healthy controls. Fourteen MHE patients
      and 14 age-and sex-matched healthy subjects underwent resting-state fMRI scans.
      ICA was used to identify six RSNs [dorsal attention network (DAN), default mode
      network (DMN), visual network (VN), auditory network (AN), sensorimotor network
      (SMN), self-referential network (SRN)] in each subject. Group maps of each RSN
      were compared between the MHE and healthy control groups. Pearson correlation
      analysis was performed between the RSNs functional connectivity (FC) and venous
      blood ammonia levels, and neuropsychological tests scores for all patients.
      Compared with the healthy controls, MHE patients showed significantly decreased
      FC in DAN, both decreased and increased FC in DMN, AN and VN. No significant
      differences were found in SRN and SMN between two groups. A relationship between
      FC and blood ammonia levels/neuropsychological tests scores were found in
      specific regions of RSNs, including middle and medial frontal gyrus, inferior
      parietal lobule, as well as anterior and posterior cingulate cortex/precuneus.
      CONCLUSIONS/SIGNIFICANCE: MHE patients have selective impairments of RSNs
      intrinsic functional connectivity, with aberrant functional connectivity in DAN,
      DMN, VN, AN, and spared SMN and SRN. Our fMRI study might supply a novel way to
      understand the neuropathophysiological mechanism of cognition function changes in
      MHE.

PMID- 22662153
TI  - Comparison of recombinant human haptocorrin expressed in human embryonic kidney
      cells and native haptocorrin.
AB  - Haptocorrin (HC) is a circulating corrinoid binding protein with unclear
      function. In contrast to transcobalamin, the other transport protein in blood, HC
      is heavily glycosylated and binds a variety of cobalamin (Cbl) analogues. HC is
      present not only in blood but also in various secretions like milk, tears and
      saliva. No recombinant form of HC has been described so far. We report the
      expression of recombinant human HC (rhHC) in human embryonic kidney cells. We
      purified the protein with a yield of 6 mg (90 nmol) per litre of cell culture
      supernatant. The isolated rhHC behaved as native HC concerning its spectral
      properties and ability to recognize both Cbl and its baseless analogue
      cobinamide. Similar to native HC isolated from blood, rhHC bound to the
      asialoglycoprotein receptor only after removal of terminal sialic acid residues
      by treatment with neuraminidase. Interestingly, rhHC, that compared to native HC
      contains four excessive amino acids (...LVPR) at the C-terminus, showed subtle
      changes in the binding kinetics of Cbl, cobinamide and the fluorescent Cbl
      conjugate CBC. The recombinant protein has properties very similar to native HC
      and although showing slightly different ligand binding kinetics, rhHC is valuable
      for further biochemical and structural studies.

PMID- 22662154
TI  - Genotype-dependent efficacy of a dual PI3K/mTOR inhibitor, NVP-BEZ235, and an
      mTOR inhibitor, RAD001, in endometrial carcinomas.
AB  - The PI3K (phosphatidylinositol-3-kinase)/mTOR (mammalian target of rapamycin)
      pathway is frequently activated in endometrial cancer through various PI3K/AKT
      activating genetic alterations. We examined the antitumor effect of NVP-BEZ235--a
      dual PI3K/mTOR inhibitor--and RAD001--an mTOR inhibitor--in 13 endometrial cancer
      cell lines, all of which possess one or more alterations in PTEN, PIK3CA, and K
      Ras. We also combined these compounds with a MAPK pathway inhibitor (PD98059 or
      UO126) in cell lines with K-Ras alterations (mutations or amplification). PTEN
      mutant cell lines without K-Ras alterations (n = 9) were more sensitive to both
      RAD001 and NVP-BEZ235 than were cell lines with K-Ras alterations (n = 4). Dose
      dependent growth suppression was more drastically induced by NVP-BEZ235 than by
      RAD001 in the sensitive cell lines. G1 arrest was induced by NVP-BEZ235 in a dose
      dependent manner. We observed in vivo antitumor activity of both RAD001 and NVP
      BEZ235 in nude mice. The presence of a MEK inhibitor, PD98059 or UO126,
      sensitized the K-Ras mutant cells to NVP-BEZ235. Robust growth suppression by NVP
      BEZ235 suggests that a dual PI3K/mTOR inhibitor is a promising therapeutic for
      endometrial carcinomas. Our data suggest that mutational statuses of PTEN and K
      Ras might be useful predictors of sensitivity to NVP-BEZ235 in certain
      endometrial carcinomas.

PMID- 22662156
TI  - Effect of fibrin glue on the biomechanical properties of human Descemet's
      membrane.
AB  - BACKGROUND: Corneal transplantation has rapidly evolved from full-thickness
      penetrating keratoplasty (PK) to selective tissue corneal transplantation, where
      only the diseased portions of the patient's corneal tissue are replaced with
      healthy donor tissue. Descemet's membrane endothelial keratoplasty (DMEK)
      performed in patients with corneal endothelial dysfunction is one such example
      where only a single layer of endothelial cells with its basement membrane (10-15
      um in thickness), Descemet's membrane (DM) is replaced. It is challenging to
      replace this membrane due to its intrinsic property to roll in an aqueous
      environment. The main objective of this study was to determine the effects of
      fibrin glue (FG) on the biomechanical properties of DM using atomic force
      microscopy (AFM) and relates these properties to membrane folding propensity.
      METHODOLOGY/PRINCIPAL FINDINGS: Fibrin glue was sprayed using the EasySpray
      applicator system, and the biomechanical properties of human DM were determined
      by AFM. We studied the changes in the "rolling up" tendency of DM by examining
      the changes in the elasticity and flexural rigidity after the application of FG.
      Surface topography was assessed using scanning electron microscopy (SEM) and AFM
      imaging. Treatment with FG not only stabilized and stiffened DM but also led to a
      significant increase in hysteresis of the glue-treated membrane. In addition,
      flexural or bending rigidity values also increased in FG-treated membranes.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that fibrin glue provides rigidity
      to the DM/endothelial cell complex that may aid in subsequent manipulation by
      maintaining tissue integrity.

PMID- 22662155
TI  - pKa modulation of the acid/base catalyst within GH32 and GH68: a role in
      substrate/inhibitor specificity?
AB  - Glycoside hydrolases of families 32 (GH32) and 68 (GH68) belong to clan GH-J,
      containing hydrolytic enzymes (sucrose/fructans as donor substrates) and
      fructosyltransferases (sucrose/fructans as donor and acceptor substrates). In
      GH32 members, some of the sugar substrates can also function as inhibitors, this
      regulatory aspect further adding to the complexity in enzyme functionalities
      within this family. Although 3D structural information becomes increasingly
      available within this clan and huge progress has been made on structure-function
      relationships, it is not clear why some sugars bind as inhibitors without being
      catalyzed. Conserved aspartate and glutamate residues are well known to act as
      nucleophile and acid/bases within this clan. Based on the available 3D structures
      of enzymes and enzyme-ligand complexes as well as docking simulations, we
      calculated the pKa of the acid-base before and after substrate binding. The
      obtained results strongly suggest that most GH-J members show an acid-base
      catalyst that is not sufficiently protonated before ligand entrance, while the
      acid-base can be fully protonated when a substrate, but not an inhibitor, enters
      the catalytic pocket. This provides a new mechanistic insight aiming at
      understanding the complex substrate and inhibitor specificities observed within
      the GH-J clan. Moreover, besides the effect of substrate entrance on its own, we
      strongly suggest that a highly conserved arginine residue (in the RDP motif)
      rather than the previously proposed Tyr motif (not conserved) provides the proton
      to increase the pKa of the acid-base catalyst.

PMID- 22662157
TI  - Genetic and phenotypic characterization of a Pseudomonas aeruginosa population
      with high frequency of genomic islands.
AB  - Various genomic islands, PAPI-1, PAPI-2, PAGI-1, PAGI-2, PAGI-3, and PAGI-4, and
      the element pKLC102 have been characterized in different P. aeruginosa strains
      from diverse habitats and geographical locations. Chromosomal DNA macroarray of
      100 P. aeruginosa strains isolated from 85 unrelated patients hospitalized in an
      intensive care unit was created to assess the occurrence of these genomic islands
      (GEIs). The macroarray was then hybridized with labeled probes derived from each
      genomic island. In addition, PFGE patterns with SpeI, frequency of virulence
      genes, and antimicrobial resistance patterns of the strains were studied. Our
      results showed that almost all P. aeruginosa strains presented up to eight
      virulence genes. By SpeI macrorestriction fragment analysis we were able to
      identify 49 restriction patterns; 35 patterns correspond to single strains and
      the remaining 14 to strains subgroup (a-n). Most of the strains showed variation
      in number or composition of GEIs and a specific antimicrobial pattern indicating
      that each strain was an unrelated isolate. In terms of the number of genomic
      islands per strain, 7 GEIs were found in 34% of the strains, 6 in 18%, 5 in 12%,
      4 in 14%, 3 in 10%, 2 in 7%, and 1 in 4%; only one isolate did not present any
      GEI. The genomic islands PAPI-1 and PAPI-2 and the element pKLC102 were the most
      frequently detected. The analysis of the location of each GEI in the chromosome
      of two strains show that the islands PAGI-3, PAPI-1, PAPI-2 and pKLC102 are
      present in the insertion site previously reported, but that PAGI-2 and PAGI-4 are
      inserted in another chromosome place in a site not characterized yet. In
      conclusion our data show that P. aeruginosa strains exhibited an epidemic
      population structure with horizontal transfer of DNA resulting in a high
      frequency of GEIs.

PMID- 22662158
TI  - Construction and validation of a systematic ethogram of Macaca fascicularis in a
      free enclosure.
AB  - Behavioral studies in non-human primates have become ideal models for further
      investigations into advanced cognitive function in humans. To date, there is no
      systematic ethogram of the cynomolgus monkey (Macaca fascicularis) in a free
      enclosure. In a field observation of 6012 subjects, 107 distinct behaviors of M.
      fascicularis were preliminarily described. 83 of these behaviors were then
      independently validated through a randomized cohort and classified into 12
      behavioral categories. 53 of these behaviors were then selected to accurately
      reflect the daily mundane activity of the species in a free enclosure. These
      findings systematically document the behavior of M. fascicularis in a free
      enclosure for use in further investigations.

PMID- 22662159
TI  - Systematic deletion of homeobox genes in Podospora anserina uncovers their roles
      in shaping the fruiting body.
AB  - Higher fungi, which comprise ascomycetes and basidiomycetes, play major roles in
      the biosphere. Their evolutionary success may be due to the extended dikaryotic
      stage of their life cycle, which is the basis for their scientific name: the
      Dikarya. Dikaryosis is maintained by similar structures, the clamp in
      basidiomycetes and the crozier in ascomycetes. Homeodomain transcription factors
      are required for clamp formation in all basidiomycetes studied. We identified all
      the homeobox genes in the filamentous ascomycete fungus Podospora anserina and
      constructed deletion mutants for each of these genes and for a number of gene
      combinations. Croziers developed normally in these mutants, including those with
      up to six deleted homeogenes. However, some mutants had defects in maturation of
      the fruiting body, an effect that could be rescued by providing wild-type
      maternal hyphae. Analysis of mutants deficient in multiple homeogenes revealed
      interactions between the genes, suggesting that they operate as a complex
      network. Similar to their role in animals and plants, homeodomain transcription
      factors in ascomycetes are involved in shaping multicellular structures.

PMID- 22662160
TI  - A common missense variant in the ATP receptor P2X7 is associated with reduced
      risk of cardiovascular events.
AB  - BACKGROUND AND PURPOSE: Extracellular adenosine triphosphate (ATP) regulates
      inflammatory cells by activation of the P2X(7) receptor. We hypothesized that
      polymorphisms in P2RX7 influence the risk of ischemic heart disease (IHD),
      ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis
      using genetic association studies. METHODS: Two loss-of-function SNPs in P2RX7
      were genotyped in 1244 IHD cases and 2488 controls as well as 5969 individuals
      with cardiovascular risk factors. Eleven SNPs in a 250 kb region on chromosome 12
      spanning P2RX7 as well as neighboring genes OASL, P2RX4 and CAMKK2 were genotyped
      in 4138 individuals with IS and 2528 controls. Association was examined using
      linear and logistic regression models with an additive genetic model. RESULTS:
      The common loss-of-function variant rs3751143 was significantly associated with a
      decreased risk of IHD in smokers (P = 0.03) as well as decreased risk of IS (OR
      0.89; 95% CI = 0.81-0.97; P = 0.012). In addition, an intronic SNP in CAMKK2,
      rs2686342, were associated with a decreased risk of IS (OR 0.89; 95% CI = 0.82
      0.97; P = 0.011). In subgroup analyses, both SNPs were associated with decreased
      risk of IS in individuals with hypertension (P = 0.045 and 0.015, respectively).
      CONCLUSIONS: A common loss-of-function missense variant in the gene encoding the
      P2X(7) receptor is associated with reduced risk of IS and with IHD in smokers.
      These findings might implicate a role of purinergic signaling in atherogenesis or
      atherothrombosis.

PMID- 22662161
TI  - SAS-Pro: simultaneous residue assignment and structure superposition for protein
      structure alignment.
AB  - Protein structure alignment is the problem of determining an assignment between
      the amino-acid residues of two given proteins in a way that maximizes a measure
      of similarity between the two superimposed protein structures. By identifying
      geometric similarities, structure alignment algorithms provide critical insights
      into protein functional similarities. Existing structure alignment tools adopt a
      two-stage approach to structure alignment by decoupling and iterating between the
      assignment evaluation and structure superposition problems. We introduce a novel
      approach, SAS-Pro, which addresses the assignment evaluation and structure
      superposition simultaneously by formulating the alignment problem as a single
      bilevel optimization problem. The new formulation does not require the
      sequentiality constraints, thus generalizing the scope of the alignment
      methodology to include non-sequential protein alignments. We employ derivative
      free optimization methodologies for searching for the global optimum of the
      highly nonlinear and non-differentiable RMSD function encountered in the proposed
      model. Alignments obtained with SAS-Pro have better RMSD values and larger
      lengths than those obtained from other alignment tools. For non-sequential
      alignment problems, SAS-Pro leads to alignments with high degree of similarity
      with known reference alignments. The source code of SAS-Pro is available for
      download at http://eudoxus.cheme.cmu.edu/saspro/SAS-Pro.html.

PMID- 22662162
TI  - Multiple SNPs in intron 41 of thyroglobulin gene are associated with autoimmune
      thyroid disease in the Japanese population.
AB  - BACKGROUND: The etiology of the autoimmune thyroid diseases (AITDs), Graves'
      disease (GD) and Hashimoto's thyroiditis (HT), is largely unknown. However,
      genetic susceptibility is believed to play a major role. Two whole genome scans
      from Japan and from the US identified a locus on chromosome 8q24 that showed
      evidence for linkage with AITD and HT. Recent studies have demonstrated an
      association between thyroglobulin (Tg) polymorphisms and AITD in Caucasians,
      suggesting that Tg is a susceptibility gene on 8q24. OBJECTIVES: The objective of
      the study was to refine Tg association with AITD, by analyzing a panel of 25 SNPs
      across an extended 260 kb region of the Tg. METHODS: We studied 458 Japanese AITD
      patients (287 GD and 171 HT patients) and 221 matched Japanese control subjects
      in association studies. Case-control association studies were performed using 25
      Tg single nucleotide polymorphisms (SNPs) chosen from a database of the Single
      Nucleotide Polymorphism Database (dbSNP). Haplotype analysis was undertaken using
      the computer program SNPAlyze version 7.0. PRINCIPAL FINDINGS AND CONCLUSIONS: In
      total, 5 SNPs revealed association with GD (P<0.05), with the strongest SNP
      associations at rs2256366 (P = 0.002) and rs2687836 (P = 0.0077), both located in
      intron 41 of the Tg gene. Because of the strong LD between these two strongest
      associated variants, we performed the haplotype analysis, and identified a major
      protective haplotype for GD (P = 0.001). These results suggested that the Tg gene
      is involved in susceptibility for GD and AITD in the Japanese.

PMID- 22662163
TI  - Validation of the Fibromyalgia Survey Questionnaire within a cross-sectional
      survey.
AB  - The Fibromyalgia Survey Questionnaire (FSQ) assesses the key symptoms of
      fibromyalgia syndrome. The FSQ can be administrated in survey research and
      settings where the use of interviews to evaluate the number of pain sites and
      extent of somatic symptom intensity and tender point examination would be
      difficult. We validated the FSQ in a cross-sectional survey with FMS patients. In
      a cross-sectional survey, participants with physician diagnosis of FMS were
      recruited by FMS-self help organisations and nine clinical institutions of
      different levels of care. Participants answered the FSQ (composed by the
      Widespread Pain Index [WPI] and the Somatic Severity Score [SSS]) assessing the
      Fibromyalgia Survey Diagnostic Criteria (FSDC) and the Patient Health
      Questionnaire PHQ 4. American College of Rheumatology 1990 classification
      criteria were assessed in a subgroup of participants. 1,651 persons diagnosed
      with FMS were included into analysis. The acceptance of the FSQ-items ranged
      between 78.9 to 98.1% completed items. The internal consistency of the items of
      the SSS ranged between 0.75-0.82. 85.5% of the study participants met the FSDC.
      The concordance rate of the FSDC and ACR 1990 criteria was 72.7% in a subsample
      of 128 patients. The Pearson correlation of the SSS with the PHQ 4 depression
      score was 0.52 (p<0.0001) and with the PHQ anxiety score was 0.51 (p<0.0001)
      (convergent validity). 64/202 (31.7%) of the participants not meeting the FSDC
      criteria and 152/1283 (11.8%) of the participants meeting the FSDC criteria
      reported an improvement (slightly too very much better) in their health status
      since FMS-diagnosis (Chi(2) = 55, p<0.0001) (discriminant validity). The study
      demonstrated the feasibility of the FSQ in a cross-sectional survey with FMS
      patients. The reliability, convergent and discriminant validity of the FSQ were
      good. Further validation studies of the FSQ in clinical and general population
      settings are necessary.

PMID- 22662164
TI  - The Sfp-type 4'-phosphopantetheinyl transferase Ppt1 of Fusarium fujikuroi
      controls development, secondary metabolism and pathogenicity.
AB  - The heterothallic ascomycete Fusarium fujikuroi is a notorious rice pathogen
      causing super-elongation of plants due to the production of terpene-derived
      gibberellic acids (GAs) that function as natural plant hormones. Additionally, F.
      fujikuroi is able to produce a variety of polyketide- and non-ribosomal peptide
      derived metabolites such as bikaverins, fusarubins and fusarins as well as
      metabolites from yet unidentified biosynthetic pathways, e.g. moniliformin. The
      key enzymes needed for their production belong to the family of polyketide
      synthases (PKSs) and non-ribosomal peptide synthases (NRPSs) that are generally
      known to be post-translationally modified by a Sfp-type 4'phosphopantetheinyl
      transferase (PPTase). In this study we provide evidence that the F. fujikuroi Sfp
      type PPTase FfPpt1 is essentially involved in lysine biosynthesis and production
      of bikaverins, fusarubins and fusarins, but not moniliformin as shown by
      analytical methods. Concomitantly, targeted Ffppt1 deletion mutants reveal an
      enhancement of terpene-derived metabolites like GAs and volatile substances such
      as alpha-acorenol. Pathogenicity assays on rice roots using fluorescent labeled
      wild-type and Ffppt1 mutant strains indicate that lysine biosynthesis and iron
      acquisition but not PKS and NRPS metabolism is essential for establishment of
      primary infections of F. fujikuroi. Additionally, FfPpt1 is involved in
      conidiation and sexual mating recognition possibly by activating PKS- and/or NRPS
      derived metabolites that could act as diffusible signals. Furthermore, the effect
      on iron acquisition of Ffppt1 mutants led us to identify a previously
      uncharacterized putative third reductive iron uptake system (FfFtr3/FfFet3) that
      is closely related to the FtrA/FetC system of A. fumigatus. Functional
      characterization provides evidence that both proteins are involved in iron
      acquisition and are liable to transcriptional repression of the homolog of the
      Aspergillus GATA-type transcription factor SreA under iron-replete conditions.
      Targeted deletion of the first Fusarium homolog of this GATA-type transcription
      factor-encoding gene, Ffsre1, strongly indicates its involvement in regulation of
      iron homeostasis and oxidative stress resistance.

PMID- 22662165
TI  - Activation of beta-catenin by oncogenic PIK3CA and EGFR promotes resistance to
      glucose deprivation by inducing a strong antioxidant response.
AB  - Glucose is an essential fuel for cell survival and its availability limits
      aberrant cellular proliferation. We have hypothesized that specific cancer
      mutations regulate metabolic response(s) to glucose deprivation (GD). By means of
      somatic knock-in cellular models, we have analyzed the response to glucose
      deprivation in cells carrying the frequent (delE746-A750)EGFR, (G13D)KRAS or
      (E545K)PIK3CA cancer alleles. We demonstrate that, in mammary epithelial cells,
      glucose has an essential antioxidant function and that these cells are very
      sensitive to GD. Conversely, isogenic cells carrying the (delE746-A750)EGFR or
      the (E545K)PIK3CA, but not the (G13D)KRAS allele, display high tolerance to GD by
      stimulating the expression of anti-oxidant genes (MnSOD and catalase). This
      adaptive transcriptional response is mediated by the activation of WNT/beta
      catenin and FOXO4 signalling. Our data highlights a new functional synergism
      between oncogenic EGFR and PIK3CA with WNT/beta-catenin conferring high tolerance
      to oxidative stress generated by nutrient deprivation.

PMID- 22662166
TI  - An ecological alternative to Snodgrass & Vanderwart: 360 high quality colour
      images with norms for seven psycholinguistic variables.
AB  - This work presents a new set of 360 high quality colour images belonging to 23
      semantic subcategories. Two hundred and thirty-six Spanish speakers named the
      items and also provided data from seven relevant psycholinguistic variables: age
      of acquisition, familiarity, manipulability, name agreement, typicality and
      visual complexity. Furthermore, we also present lexical frequency data derived
      from Internet search hits. Apart from the high number of variables evaluated,
      knowing that it affects the processing of stimuli, this new set presents
      important advantages over other similar image corpi: (a) this corpus presents a
      broad number of subcategories and images; for example, this will permit
      researchers to select stimuli of appropriate difficulty as required, (e.g., to
      deal with problems derived from ceiling effects); (b) the fact of using coloured
      stimuli provides a more realistic, ecologically-valid, representation of real
      life objects. In sum, this set of stimuli provides a useful tool for research on
      visual object- and word-processing, both in neurological patients and in healthy
      controls.

PMID- 22662167
TI  - Genetic variation in the EGFR gene and the risk of glioma in a Chinese Han
      population.
AB  - Previous studies have shown that regulation of the epidermal growth factor gene
      (EGFR) pathway plays a role in glioma progression. Certain genotypes of the EGFR
      gene may be related to increased glioblastoma risk, indicating that germ line
      EGFR polymorphisms may have implications in carcinogenesis. To examine whether
      and how variants in the EGFR gene contribute to glioma susceptibility, we
      evaluated nine tagging single-nucleotide polymorphisms (tSNPs) of the EGFR gene
      in a case-control study from Xi'an city of China (301 cases, 302 controls). EGFR
      SNP associations analyses were performed using SPSS 16.0 statistical packages,
      PLINK software, Haploview software package (version 4.2) and SHEsis software
      platform. We identified two susceptibility tSNPs in the EGFR gene that were
      potentially associated with an increased risk of glioma (rs730437, p = 0.016; OR:
      1.32; 95%CI: 1.05-1.66 and rs1468727, p = 0.008; OR: 1.31; 95%CI: 1.04-1.65).
      However, after a strict Bonferroni correction analysis was applied, the
      significance level of the association between EGFR tSNPs and risk of glioma was
      attenuated. We observed a protective effect of haplotype "AATT" of the EGFR gene,
      which was associated with a 29% reduction in the risk of developing glioma, while
      haplotype "CGTC" increased the risk of developing glioma by 36%. Our results,
      combined with previous studies, suggested an association between the EGFR gene
      and glioma development.

PMID- 22662168
TI  - Nutrient intakes linked to better health outcomes are associated with higher diet
      costs in the US.
AB  - PURPOSE: Degrees of nutrient intake and food groups have been linked to
      differential chronic disease risk. However, intakes of specific nutrients may
      also be associated with differential diet costs and unobserved differences in
      socioeconomic status (SES). The present study examined degrees of nutrient
      intake, for every key nutrient in the diet, in relation to diet cost and SES.
      METHODS: Socio-demographic data for a stratified random sample of adult
      respondents in the Seattle Obesity Study were obtained through telephone survey.
      Dietary intakes were assessed using food frequency questionnaire (FFQ) (n =
      1,266). Following standard procedures, nutrient intakes were energy-adjusted
      using the residual method and converted into quintiles. Diet cost for each
      respondent was estimated using Seattle supermarket retail prices for 384 FFQ
      component foods. RESULTS: Higher intakes of dietary fiber, vitamins A, C, D, E,
      and B12, beta carotene, folate, iron, calcium, potassium, and magnesium were
      associated with higher diet costs. The cost gradient was most pronounced for
      vitamin C, beta carotene, potassium, and magnesium. Higher intakes of saturated
      fats, trans fats and added sugars were associated with lower diet costs. Lower
      cost lower quality diets were more likely to be consumed by lower SES.
      CONCLUSION: Nutrients commonly associated with a lower risk of chronic disease
      were associated with higher diet costs. By contrast, nutrients associated with
      higher disease risk were associated with lower diet costs. The cost variable may
      help somewhat explain why lower income groups fail to comply with dietary
      guidelines and have highest rates of diet related chronic disease.

PMID- 22662169
TI  - Evaluation of the effectiveness of light streamer tori-lines and characteristics
      of bait attacks by seabirds in the western North Pacific.
AB  - To improve the effectiveness of tori-lines it is necessary to evaluate the
      ability of tori-lines to mitigate seabird bycatch and determine what kind of
      seabird species gather during line settings, attack the bait and are incidentally
      caught. We conducted two experiments in the western North Pacific and examined
      the effectiveness for seabird mitigation of light streamer tori-lines which have
      no long streamers but many light (short) streamers and are mainly used in the
      North Pacific area. Firstly, the effectiveness of two different types of tori
      line (light streamer (1 m) and long streamer (up to 7 m) tori-line) and of two
      different colors (yellow and red) of light streamers for seabird bycatch
      avoidance was evaluated using 567 sets based on data from 20 offshore surface
      commercial longliners. No significant difference in the bycatch number between
      the different tori-line types and streamer colors was found. Secondly, we
      investigated the characteristics of the seabird bycatch in the North Pacific and
      the effectiveness of three different types of streamers (light, hybrid and
      modified light types) by detailed observations of seabird attacks using a
      chartered longline vessel. Although the appearance rate of albatrosses and
      shearwaters were 40.9% and 27.7%, Laysan albatross was the main seabird species
      that followed the vessel but shearwaters seldom followed the vessel and did not
      aggregate during line setting. In all attacks on bait observed during line
      settings, 81% and 7% were by albatrosses and shearwaters, respectively. In the
      number of primary attacks by Laysan albatrosses which attacked most aggressively
      of all seabirds, there were no significant differences among the tori-line types.
      No individuals of shearwater were caught. The results of both experiments
      indicated that light streamer tori-lines were as effective as tori-lines with
      long streamers for mitigating seabird bycatch in the North Pacific.

PMID- 22662170
TI  - Pyrosequencing-based comparative genome analysis of Vibrio vulnificus
      environmental isolates.
AB  - Between 1996 and 2006, the US Centers for Disease Control reported that the only
      category of food-borne infections increasing in frequency were those caused by
      members of the genus Vibrio. The gram-negative bacterium Vibrio vulnificus is a
      ubiquitous inhabitant of estuarine waters, and is the number one cause of seafood
      related deaths in the US. Many V. vulnificus isolates have been studied, and it
      has been shown that two genetically distinct subtypes, distinguished by 16S rDNA
      and other gene polymorphisms, are associated predominantly with either
      environmental or clinical isolation. While local genetic differences between the
      subtypes have been probed, only the genomes of clinical isolates have so far been
      completely sequenced. In order to better understand V. vulnificus as an agent of
      disease and to identify the molecular components of its virulence mechanisms, we
      have completed whole genome shotgun sequencing of three diverse environmental
      genotypes using a pyrosequencing approach. V. vulnificus strain JY1305 was
      sequenced to a depth of 33*, and strains E64MW and JY1701 were sequenced to
      lesser depth, covering approximately 99.9% of each genome. We have performed a
      comparative analysis of these sequences against the previously published
      sequences of three V. vulnificus clinical isolates. We find that the genome of V.
      vulnificus is dynamic, with 1.27% of genes in the C-genotype genomes not found in
      the E- genotype genomes. We identified key genes that differentiate between the
      genomes of the clinical and environmental genotypes. 167 genes were found to be
      specifically associated with environmental genotypes and 278 genes with clinical
      genotypes. Genes specific to the clinical strains include components of sialic
      acid catabolism, mannitol fermentation, and a component of a Type IV secretory
      pathway VirB4, as well as several other genes with potential significance for
      human virulence. Genes specific to environmental strains included several that
      may have implications for the balance between self-preservation under stress and
      nutritional competence.

PMID- 22662171
TI  - Dopamine induced neurodegeneration in a PINK1 model of Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease is a common neurodegenerative disease
      characterised by progressive loss of dopaminergic neurons, leading to dopamine
      depletion in the striatum. Mutations in the PINK1 gene cause an autosomal
      recessive form of Parkinson's disease. Loss of PINK1 function causes
      mitochondrial dysfunction, increased reactive oxygen species production and
      calcium dysregulation, which increases susceptibility to neuronal death in
      Parkinson's disease. The basis of neuronal vulnerability to dopamine in
      Parkinson's disease is not well understood. METHODOLOGY: We investigated the
      mechanism of dopamine induced cell death in transgenic PINK1 knockout mouse
      neurons. We show that dopamine results in mitochondrial depolarisation caused by
      mitochondrial permeability transition pore (mPTP) opening. Dopamine-induced mPTP
      opening is dependent on a complex of reactive oxygen species production and
      calcium signalling. Dopamine-induced mPTP opening, and dopamine-induced cell
      death, could be prevented by inhibition of reactive oxygen species production, by
      provision of respiratory chain substrates, and by alteration in calcium
      signalling. CONCLUSIONS: These data demonstrate the mechanism of dopamine
      toxicity in PINK1 deficient neurons, and suggest potential therapeutic strategies
      for neuroprotection in Parkinson's disease.

PMID- 22662172
TI  - Sequence-based genotyping for marker discovery and co-dominant scoring in
      germplasm and populations.
AB  - Conventional marker-based genotyping platforms are widely available, but not
      without their limitations. In this context, we developed Sequence-Based
      Genotyping (SBG), a technology for simultaneous marker discovery and co-dominant
      scoring, using next-generation sequencing. SBG offers users several advantages
      including a generic sample preparation method, a highly robust genome complexity
      reduction strategy to facilitate de novo marker discovery across entire genomes,
      and a uniform bioinformatics workflow strategy to achieve genotyping goals
      tailored to individual species, regardless of the availability of a reference
      sequence. The most distinguishing features of this technology are the ability to
      genotype any population structure, regardless whether parental data is included,
      and the ability to co-dominantly score SNP markers segregating in populations. To
      demonstrate the capabilities of SBG, we performed marker discovery and genotyping
      in Arabidopsis thaliana and lettuce, two plant species of diverse genetic
      complexity and backgrounds. Initially we obtained 1,409 SNPs for arabidopsis, and
      5,583 SNPs for lettuce. Further filtering of the SNP dataset produced over 1,000
      high quality SNP markers for each species. We obtained a genotyping rate of 201.2
      genotypes/SNP and 58.3 genotypes/SNP for arabidopsis (n = 222 samples) and
      lettuce (n = 87 samples), respectively. Linkage mapping using these SNPs resulted
      in stable map configurations. We have therefore shown that the SBG approach
      presented provides users with the utmost flexibility in garnering high quality
      markers that can be directly used for genotyping and downstream applications.
      Until advances and costs will allow for routine whole-genome sequencing of
      populations, we expect that sequence-based genotyping technologies such as SBG
      will be essential for genotyping of model and non-model genomes alike.

PMID- 22662173
TI  - Allelic variations of a light harvesting chlorophyll a/b-binding protein gene
      (Lhcb1) associated with agronomic traits in barley.
AB  - Light-harvesting chlorophyll a/b-binding protein (LHCP) is one of the most
      abundant chloroplast proteins in plants. Its main function is to collect and
      transfer light energy to photosynthetic reaction centers. However, the roles of
      different LHCPs in light-harvesting antenna systems remain obscure. Exploration
      of nucleotide variation in the genes encoding LHCP can facilitate a better
      understanding of the functions of LHCP. In this study, nucleotide variations in
      Lhcb1, a LHCP gene in barley, were investigated across 292 barley accessions
      collected from 35 different countries using EcoTILLING technology, a variation of
      the Targeting Induced Local Lesions In Genomes (TILLING). A total of 23
      nucleotide variations were detected including three insert/deletions (indels) and
      20 single nucleotide polymorphisms (SNPs). Among them, 17 SNPs were in the coding
      region with nine missense changes. Two SNPs with missense changes are predicted
      to be deleterious to protein function. Seventeen SNP formed 31 distinguishable
      haplotypes in the barley collection. The levels of nucleotide diversity in the
      Lhcb1 locus differed markedly with geographic origins and species of accessions.
      The accessions from Middle East Asia exhibited the highest nucleotide and
      haplotype diversity. H. spontaneum showed greater nucleotide diversity than H.
      vulgare. Five SNPs in Lhcb1 were significantly associated with at least one of
      the six agronomic traits evaluated, namely plant height, spike length, number of
      grains per spike, thousand grain weight, flag leaf area and leaf color, and these
      SNPs may be used as potential markers for improvement of these barley traits.

PMID- 22662174
TI  - MRI tracking of FePro labeled fresh and cryopreserved long term in vitro expanded
      human cord blood AC133+ endothelial progenitor cells in rat glioma.
AB  - BACKGROUND: Endothelial progenitors cells (EPCs) are important for the
      development of cell therapies for various diseases. However, the major obstacles
      in developing such therapies are low quantities of EPCs that can be generated
      from the patient and the lack of adequate non-invasive imaging approach for in
      vivo monitoring of transplanted cells. The objective of this project was to
      determine the ability of cord blood (CB) AC133+ EPCs to differentiate, in vitro
      and in vivo, toward mature endothelial cells (ECs) after long term in vitro
      expansion and cryopreservation and to use magnetic resonance imaging (MRI) to
      assess the in vivo migratory potential of ex vivo expanded and cryopreserved CB
      AC133+ EPCs in an orthotopic glioma rat model. MATERIALS, METHODS AND RESULTS:
      The primary CB AC133+ EPC culture contained mainly EPCs and long term in vitro
      conditions facilitated the maintenance of these cells in a state of commitment
      toward endothelial lineage. At days 15-20 and 25-30 of the primary culture, the
      cells were labeled with FePro and cryopreserved for a few weeks. Cryopreserved
      cells were thawed and in vitro differentiated or i.v. administered to glioma
      bearing rats. Different groups of rats also received long-term cultured,
      magnetically labeled fresh EPCs and both groups of animals underwent MRI 7 days
      after i.v. administration of EPCs. Fluorescent microscopy showed that in vitro
      differentiation of EPCs was not affected by FePro labeling and cryopreservation.
      MRI analysis demonstrated that in vivo accumulation of previously cryopreserved
      transplanted cells resulted in significantly higher R2 and R2* values indicating
      a higher rate of migration and incorporation into tumor neovascularization of
      previously cryopreserved CB AC133+ EPCs to glioma sites, compared to non
      cryopreserved cells. CONCLUSION: Magnetically labeled CB EPCs can be in vitro
      expanded and cryopreserved for future use as MRI probes for monitoring the
      migration and incorporation to the sites of neovascularization.

PMID- 22662175
TI  - Oligonucleotide microarray analysis of dietary-induced hyperlipidemia gene
      expression profiles in miniature pigs.
AB  - BACKGROUND: Hyperlipidemia animal models have been established, but complete gene
      expression profiles of the transition from normal lipid levels have not been
      obtained. Miniature pigs are useful model animals for gene expression studies on
      dietary-induced hyperlipidemia because they have a similar anatomy and digestive
      physiology to humans, and blood samples can be obtained from them repeatedly.
      METHODOLOGY: Two typical dietary treatments were used for dietary-induced
      hyperlipidemia models, by using specific pathogen-free (SPF) Clawn miniature
      pigs. One was a high-fat and high-cholesterol diet (HFCD) and the other was a
      high-fat, high-cholesterol, and high-sucrose diet (HFCSD). Microarray analyses
      were conducted from whole blood samples during the dietary period and from white
      blood cells at the end of the dietary period to evaluate the transition of
      expression profiles of the two dietary models. PRINCIPAL FINDINGS: Variations in
      whole blood gene expression intensity within the HFCD or the HFCSD group were in
      the same range as the controls provide with normal diet at all periods. This
      indicates uniformity of dietary-induced hyperlipidemia for our dietary protocols.
      Gene ontology- (GO) based functional analyses revealed that characteristics of
      the common changes between HFCD and HFCSD were involved in inflammatory responses
      and reproduction. The correlation coefficient between whole blood and white blood
      cell expression profiles at 27 weeks with the HFCSD diet was significantly lower
      than that of the control and HFCD diet groups. This may be due to the effects of
      RNA originating from the tissues and/or organs. CONCLUSIONS: No statistically
      significant differences in fasting plasma lipids and glucose levels between the
      HFCD and HFCSD groups were observed. However, blood RNA analyses revealed
      different characteristics corresponding to the dietary protocols. In this study,
      whole blood RNA analyses proved to be a useful tool to evaluate transitions in
      dietary-induced hyperlipidemia gene expression profiles in miniature pigs.

PMID- 22662176
TI  - Analytical framework for identifying and differentiating recent hitchhiking and
      severe bottleneck effects from multi-locus DNA sequence data.
AB  - Hitchhiking and severe bottleneck effects have impact on the dynamics of genetic
      diversity of a population by inducing homogenization at a single locus and at the
      genome-wide scale, respectively. As a result, identification and differentiation
      of the signatures of such events from DNA sequence data at a single locus is
      challenging. This paper develops an analytical framework for identifying and
      differentiating recent homogenization events at multiple neutral loci in low
      recombination regions. The dynamics of genetic diversity at a locus after a
      recent homogenization event is modeled according to the infinite-sites mutation
      model and the Wright-Fisher model of reproduction with constant population size.
      In this setting, I derive analytical expressions for the distribution, mean, and
      variance of the number of polymorphic sites in a random sample of DNA sequences
      from a locus affected by a recent homogenization event. Based on this framework,
      three likelihood-ratio based tests are presented for identifying and
      differentiating recent homogenization events at multiple loci. Lastly, I apply
      the framework to two data sets. First, I consider human DNA sequences from four
      non-coding loci on different chromosomes for inferring evolutionary history of
      modern human populations. The results suggest, in particular, that recent
      homogenization events at the loci are identifiable when the effective human
      population size is 50,000 or greater in contrast to 10,000, and the estimates of
      the recent homogenization events are agree with the "Out of Africa" hypothesis.
      Second, I use HIV DNA sequences from HIV-1-infected patients to infer the times
      of HIV seroconversions. The estimates are contrasted with other estimates derived
      as the mid-time point between the last HIV-negative and first HIV-positive
      screening tests. The results show that significant discrepancies can exist
      between the estimates.

PMID- 22662177
TI  - Early identification of HIV: empirical support for jail-based screening.
AB  - BACKGROUND: Although routine HIV testing is recommended for jails, little
      empirical data exist describing newly diagnosed individuals in this setting.
      METHODS: Client-level data (CLD) are available on a subset of individuals served
      in EnhanceLink, for the nine of the 10 sites who enrolled newly diagnosed persons
      in the client level evaluation. In addition to information about time of
      diagnosis, we analyzed data on initial CD4 count, use of antiretroviral therapy
      (ART), and linkage to care post discharge. Baseline data from newly diagnosed
      persons were compared to data from persons whose diagnoses predated jail
      admission. RESULTS: CLD were available for 58 newly diagnosed and 708 previously
      diagnosed individuals enrolled between 9/08 and 3/11. Those newly diagnosed had a
      significantly younger median age (34 years) when compared to those previously
      diagnosed (41 years). In the 30 days prior to incarceration, 11% of those newly
      diagnosed reported injection drug use and 29% reported unprotected anal
      intercourse. Median CD4 count at diagnosis was 432 cells/mL (range: 22-1,453
      cells/mL). A minority (21%, N = 12) of new diagnoses started antiretroviral
      treatment (ART) before release; 74% have evidence of linkage to community
      services. CONCLUSION: Preliminary results from a cross-sectional analysis of this
      cohort suggest testing in jails finds individuals early on in disease
      progression. Most HIV(+) detainees did not start ART in jail; therefore screening
      may not increase pharmacy costs for jails. Detainees newly diagnosed with HIV in
      jails can be effectively linked to community resources. Jail-based HIV testing
      should be a cornerstone of "test and treat" strategies.

PMID- 22662178
TI  - Methamphetamine and inflammatory cytokines increase neuronal Na+/K+-ATPase
      isoform 3: relevance for HIV associated neurocognitive disorders.
AB  - Methamphetamine (METH) abuse in conjunction with human immunodeficiency virus
      (HIV) exacerbates neuropathogenesis and accelerates neurocognitive impairments in
      the central nervous system (CNS), collectively termed HIV Associated
      Neurocognitive Disorders (HAND). Since both HIV and METH have been implicated in
      altering the synaptic architecture, this study focused on investigating
      alterations in synaptic proteins. Employing a quantitative proteomics approach on
      synaptosomes isolated from the caudate nucleus from two groups of rhesus monkeys
      chronically infected with simian immunodeficiency virus (SIV) differing by one
      regimen, METH treatment, we identified the neuron specific Na(+)/K(+)-ATPase
      alpha 1 isoform 3 (ATP1A3) to be up regulated after METH treatment, and validated
      its up regulation by METH in vitro. Further studies on signaling mechanisms
      revealed that the activation of ATP1A3 involves the extracellular regulated
      kinase (ERK) pathway. Given its function in maintaining ionic gradients and
      emerging role as a signaling molecule, changes in ATP1A3 yields insights into the
      mechanisms associated with HAND and interactions with drugs of abuse.

PMID- 22662179
TI  - Moraxella catarrhalis activates murine macrophages through multiple toll like
      receptors and has reduced clearance in lungs from TLR4 mutant mice.
AB  - Moraxella catarrhalis is a gram negative bacterium and a leading causative agent
      of otitis media (OM) in children. Several recent reports have provided strong
      evidence for an association between toll like receptors and OM. It has been found
      that both Streptococcus pneumoniae and nontypeable Haemophilus influenzae
      activate host protective immune responses through toll like receptors (TLRs),
      however, the precise mechanism by which Moraxella catarrhalis initiates the host
      immune response is currently unknown. In this report, using murine macrophages
      generated from a series of knock-out mice, we have demonstrated that M.
      catarrhalis lipooligosaccharide (LOS) and either heat killed or live bacteria are
      recognized by one or more TLRs. LOS activates the host immune response through a
      membrane bound CD14-TLR4 complex, while both heat killed and live M.cat require
      recognition by multiple toll like receptors such as TLR2, TLR4 and TLR9 without
      the requirement of CD14. We have also shown that M.cat stimuli are capable of
      triggering the host innate immune response by both MyD88- and TRIF- dependent
      signaling pathways. We further showed that M.cat induced activation of mitogen
      activated protein kinase (MAPK) is essential in order to achieve optimal
      secretion of pro-inflammatory cytokine TNF-alpha. We finally showed that TLR4
      mutant C3H/HeJ mice produce significantly lower levels of pro-inflammatory
      cytokines TNF-alpha and IL-6 in vivo, An increased bacterial loads at 12 and 24
      hours (P<0.001) in their lungs upon challenge with live M.cat in an aerosol
      chamber compared to wild-type (WT) control mice. These data suggest that TLRs are
      crucial for an effective innate immune response induced by M.cat. The results of
      these studies contribute to an increased understanding of molecular mechanism and
      possible novel treatment strategies for diseases caused by M.cat by specifically
      targeting TLRs and their signaling pathways.

PMID- 22662180
TI  - Functional analysis of a breast cancer-associated mutation in the intracellular
      domain of the metalloprotease ADAM12.
AB  - A recently identified breast cancer-associated mutation in the metalloprotease
      ADAM12 alters a potential dileucine trafficking signal, which could affect
      protein processing and cellular localization. ADAM12 belongs to the group of A
      Disintegrin And Metalloproteases (ADAMs), which are typically membrane-associated
      proteins involved in ectodomain shedding, cell-adhesion, and signaling. ADAM12 as
      well as several members of the ADAM family are over-expressed in various cancers,
      correlating with disease stage. Three breast cancer-associated somatic mutations
      were previously identified in ADAM12, and two of these, one in the
      metalloprotease domain and another in the disintegrin domain, were investigated
      and found to result in protein misfolding, retention in the secretory pathway,
      and failure of zymogen maturation. The third mutation, p.L792F in the ADAM12
      cytoplasmic tail, was not investigated, but is potentially significant given its
      location within a di-leucine motif, which is recognized as a potential cellular
      trafficking signal. The present study was motivated both by the potential
      relevance of this documented mutation to cancer, as well as for determining the
      role of the di-leucine motif in ADAM12 trafficking. Expression of ADAM12 p.L792F
      in mammalian cells demonstrated quantitatively similar expression levels and
      zymogen maturation as wild-type (WT) ADAM12, as well as comparable cellular
      localizations. A cell surface biotinylation assay demonstrated that cell surface
      levels of ADAM12 WT and ADAM12 p.L792F were similar and that internalization of
      the mutant occurred at the same rate and extent as for ADAM12 WT. Moreover,
      functional analysis revealed no differences in cell proliferation or ectodomain
      shedding of epidermal growth factor (EGF), a known ADAM12 substrate between WT
      and mutant ADAM12. These data suggest that the ADAM12 p.L792F mutation is
      unlikely to be a driver (cancer causing)-mutation in breast cancer.

PMID- 22662181
TI  - CD36 inhibitors reduce postprandial hypertriglyceridemia and protect against
      diabetic dyslipidemia and atherosclerosis.
AB  - CD36 is recognized as a lipid and fatty acid receptor and plays an important role
      in the metabolic syndrome and associated cardiac events. The pleiotropic activity
      and the multiple molecular associations of this scavenger receptor with membrane
      associated molecules in different cells and tissues have however questioned its
      potential as a therapeutic target. The present study shows that it is possible to
      identify low molecular weight chemicals that can block the CD36 binding and
      uptake functions. These inhibitors were able to reduce arterial lipid deposition,
      fatty acid intestinal transit, plasma concentration of triglycerides and glucose,
      to improve insulin sensitivity, glucose tolerance and to reduce the plasma
      concentration of HbAc1 in different and independent rodent models. Correlation
      between the anti-CD36 activity of these inhibitors and the known
      pathophysiological activity of this scavenger receptor in the development of
      atherosclerosis and diabetes were observed at pharmacological doses. Thus, CD36
      might represent an attractive therapeutic target.

PMID- 22662182
TI  - The Arg233Lys AQP0 mutation disturbs aquaporin0-calmodulin interaction causing
      polymorphic congenital cataract.
AB  - Calmodulin (CaM) directly interacts with the aquaporin 0 (AQP0) C-terminus in a
      calcium dependent manner to regulate the water permeability of AQP0. We
      previously identified a missense mutation (p.R233K) in the putative CaM binding
      domain of AQP0 C-terminus in a congenital cataract family. This study was aimed
      at exploring the potential pathogenesis of this mutation causative of cataract
      and mainly identifying how it influenced the binding of AQP0 to CaM. Wild type
      and R233K mutant AQP0 with EGFP-tag were transfected separately into Hela cells
      to determine the expression and subcellular localizations. The co
      immunoprecipitation (CoIP) assay was used to detect the interaction between AQP0
      and CaM. AQP0 C-terminus peptides were synthesized with and without R233K, and
      the binding abilities of these peptides to CaM were assessed using a fluorescence
      binding assay. Localizations of wild type and R233K mutant AQP0 were determined
      from EGFP fluorescence, and the chimeric proteins were both localized abundantly
      in the plasma membrane. Protein expression levels of the culture cells showed no
      significant difference between them. The results from CoIP assay implied that
      R233K mutant presented more weakly in association with CaM than wild type AQP0.
      The AQP0 C-terminal mutant peptide was found to have 2.5-fold lower binding
      affinity to CaM than wild type peptide. These results suggested that R233K
      mutation did not affect the expression, location and trafficking of the protein
      but did influence the interaction between AQP0 and CaM. The binding affinity of
      AQP0 C-terminus to CaM was significantly reduced. Due to lack of the modulation
      of the Ca2+-calmodulin complex, the water permeability of AQP0 was subsequently
      augmented, which might lead to the development of this cataract.

PMID- 22662183
TI  - Efficient asymmetric reduction of 4-(trimethylsilyl)-3-butyn-2-one by Candida
      parapsilosis cells in an ionic liquid-containing system.
AB  - Hydrophilic ionic liquids (ILs) were employed as green solvents to construct an
      IL-containing co-solvent system for improving the asymmetric reduction of 4
      (trimethylsilyl)-3-butyn-2-one by immobilized Candida parapsilosis cells. Among
      14 hydrophilic ILs examined, 1-(2'-hydroxyl)ethyl-3-methylimidazolium nitrate
      (C(2)OHMIM.NO(3)) was considered as the most suitable IL for the bioreduction
      with the fastest initial reaction rate, the highest yield and the highest product
      e.e., which may be due to the good biocompatibility with the cells. For a better
      understanding of the bioreduction performed in the C(2)OHMIM.NO(3)-containing co
      solvent system, the effects of several crucial variables were systematically
      investigated. The optimal C(2)OHMIM.NO(3) content, substrate concentration,
      buffer pH, co-substrate concentration and temperature were 10% (v/v), 3.0 mmol/L,
      5.0, 98.1 mmol/L and 30 degrees C, respectively. Under the optimal conditions,
      the initial reaction rate, the maximum yield and the product e.e. were 17.3
      umol/h g(cell), 95.2% and >99.9%, respectively, which are much better than the
      corresponding results previously reported. Moreover, the immobilized cells
      remained more than 83% of their initial activity even after being used repeatedly
      for 10 batches in the C(2)OHMIM.NO(3)-containing system, exhibiting excellent
      operational stability.

PMID- 22662184
TI  - Globalization and loss of plant knowledge: challenging the paradigm.
AB  - The erosion of cultural knowledge and traditions as a result of globalization and
      migration is a commonly reported phenomenon. We compared one type of cultural
      knowledge about medicinal plants (number of plants reported to treat thirty
      common health conditions) among Dominican laypersons who self-medicate with
      plants and live in rural or urban areas of the Dominican Republic (DR), and those
      who have moved to New York City (NYC). Many plants used as medicines were popular
      Dominican food plants. These plants were reported significantly more often by
      Dominicans living in NYC as compared to the DR, and this knowledge was not age
      dependent. These results contradict the popular paradigm about loss of cultural
      plant knowledge and is the first study to report a statistically measurable
      increase in this type of knowledge associated with migration.

PMID- 22662186
TI  - Whitebark pine stand condition, tree abundance, and cone production as predictors
      of visitation by Clark's nutcracker.
AB  - BACKGROUND: Accurately quantifying key interactions between species is important
      for developing effective recovery strategies for threatened and endangered
      species. Whitebark pine (Pinus albicaulis), a candidate species for listing under
      the Endangered Species Act, depends on Clark's nutcracker (Nucifraga columbiana)
      for seed dispersal. As whitebark pine succumbs to exotic disease and mountain
      pine beetles (Dendroctonus ponderosae), cone production declines, and nutcrackers
      visit stands less frequently, reducing the probability of seed dispersal.
      METHODOLOGY/PRINCIPAL FINDINGS: We quantified whitebark pine forest structure,
      health metrics, and the frequency of nutcracker occurrence in national parks
      within the Northern and Central Rocky Mountains in 2008 and 2009. Forest health
      characteristics varied between the two regions, with the northern region in
      overall poorer health. Using these data, we show that a previously published
      model consistently under-predicts the proportion of survey hours resulting in
      nutcracker observations at all cone density levels. We present a new statistical
      model of the relationship between whitebark pine cone production and the
      probability of Clark's nutcracker occurrence based on combining data from this
      study and the previous study. CONCLUSIONS/SIGNIFICANCE: Our model clarified
      earlier findings and suggested a lower cone production threshold value for
      predicting likely visitation by nutcrackers: Although nutcrackers do visit
      whitebark pine stands with few cones, the probability of visitation increases
      with increased cone production. We use information theoretics to show that beta
      regression is a more appropriate statistical framework for modeling the
      relationship between cone density and proportion of survey time resulting in
      nutcracker observations. We illustrate how resource managers may apply this model
      in the process of prioritizing areas for whitebark pine restoration.

PMID- 22662185
TI  - Gender differences in associations of glutamate decarboxylase 1 gene (GAD1)
      variants with panic disorder.
AB  - BACKGROUND: Panic disorder is common (5% prevalence) and females are twice as
      likely to be affected as males. The heritable component of panic disorder is
      estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the
      synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to
      influence various mental disorders, including mood and anxiety disorders. In a
      recent association study in depression, which is highly comorbid with panic
      disorder, GAD1 risk allele associations were restricted to females.
      METHODOLOGY/PRINCIPAL FINDINGS: Nineteen single nucleotide polymorphisms (SNPs)
      tagging the common variation in GAD1 were genotyped in two independent gender and
      age matched case-control samples (discovery sample n = 478; replication sample n
      = 584). Thirteen SNPs passed quality control and were examined for gender
      specific enrichment of risk alleles associated with panic disorder by using
      logistic regression including a genotype*gender interaction term. The latter was
      found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034,
      rs2241165) in the discovery sample; of note, the respective minor/risk alleles
      were associated with panic disorder only in females. These findings were not
      confirmed in the replication sample; however, the genotype*gender interaction of
      rs3749034 remained significant in the combined sample. Furthermore, this
      polymorphism showed a nominally significant association with the Agoraphobic
      Cognitions Questionnaire sum score. CONCLUSIONS/SIGNIFICANCE: The present study
      represents the first systematic evaluation of gender-specific enrichment of risk
      alleles of the common SNP variation in the panic disorder candidate gene GAD1.
      Our tentative results provide a possible explanation for the higher
      susceptibility of females to panic disorder.

PMID- 22662187
TI  - Efficiency of organelle capture by microtubules as a function of centrosome
      nucleation capacity: general theory and the special case of polyspermia.
AB  - Transport of organelles along microtubules is essential for the cell metabolism
      and morphogenesis. The presented analysis derives the probability that an
      organelle of a given size comes in contact with the microtubule aster. The
      question is asked how this measure of functionality of the microtubule aster is
      controlled by the centrosome. A quantitative model is developed to address this
      question. It is shown that for the given set of cellular parameters, such as size
      and total tubulin content, a centrosome nucleation capacity exists that maximizes
      the probability of the organelle capture. The developed general model is then
      applied to the capture of the female pronucleus by microtubules assembled on the
      sperm centrosome, following physiologically polyspermic fertilization. This
      application highlights an unintuitive reflection of nonlinearity of the nucleated
      polymerization of the cellular pool of tubulin. The prediction that the sperm
      centrosome should lower its nucleation capacity in the face of the competition
      from the other sperm is a stark illustration of the new optimality principle.
      Overall, the model calls attention to the capabilities of the centrosomal pathway
      of regulation of the transport-related functionality of the microtubule
      cytoskeleton. It establishes a quantitative and conceptual framework that can
      guide experiment design and interpretation.

PMID- 22662188
TI  - Radiation induces acute alterations in neuronal function.
AB  - Every year, nearly 200,000 patients undergo radiation for brain tumors. For both
      patients and caregivers the most distressing adverse effect is impaired
      cognition. Efforts to protect against this debilitating effect have suffered from
      inadequate understanding of the cellular mechanisms of radiation damage. In the
      past it was accepted that radiation-induced normal tissue injury resulted from a
      progressive reduction in the survival of clonogenic cells. Moreover, because
      radiation-induced brain dysfunction is believed to evolve over months to years,
      most studies have focused on late changes in brain parenchyma. However,
      clinically, acute changes in cognition are also observed. Because neurons are
      fully differentiated post-mitotic cells, little information exists on the acute
      effects of radiation on synaptic function. The purpose of our study was to assess
      the potential acute effects of radiation on neuronal function utilizing ex vivo
      hippocampal brain slices. The cellular localization and functional status of
      excitatory and inhibitory neurotransmitter receptors was identified by
      immunoblotting. Electrophysiological recordings were obtained both for
      populations of neuronal cells and individual neurons. In the dentate gyrus region
      of isolated ex vivo slices, radiation led to early decreases in tyrosine
      phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs)
      from the cell surface while simultaneously increasing the surface expression of
      inhibitory gamma-aminobutyric acid receptors (GABA(A)Rs). These alterations in
      cellular localization corresponded with altered synaptic responses and inhibition
      of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked
      these radiation-induced alterations in cellular distribution. These findings
      demonstrate acute effects of radiation on neuronal cells within isolated brain
      slices and open new avenues for study.

PMID- 22662189
TI  - Lipopolysaccharide O-antigen prevents phagocytosis of Vibrio anguillarum by
      rainbow trout (Oncorhynchus mykiss) skin epithelial cells.
AB  - Colonization of host tissues is a first step taken by many pathogens during the
      initial stages of infection. Despite the impact of bacterial disease on wild and
      farmed fish, only a few direct studies have characterized bacterial factors
      required for colonization of fish tissues. In this study, using live-cell and
      confocal microscopy, rainbow trout skin epithelial cells, the main structural
      component of the skin epidermis, were demonstrated to phagocytize bacteria.
      Mutant analyses showed that the fish pathogen Vibrio anguillarum required the
      lipopolysaccharide O-antigen to evade phagocytosis and that O-antigen transport
      required the putative wzm-wzt-wbhA operon, which encodes two ABC polysaccharide
      transporter proteins and a methyltransferase. Pretreatment of the epithelial
      cells with mannose prevented phagocytosis of V. anguillarum suggesting that a
      mannose receptor is involved in the uptake process. In addition, the O-antigen
      transport mutants could not colonize the skin but they did colonize the
      intestines of rainbow trout. The O-antigen polysaccharides were also shown to aid
      resistance to the antimicrobial factors, lysozyme and polymyxin B. In summary,
      rainbow trout skin epithelial cells play a role in the fish innate immunity by
      clearing bacteria from the skin epidermis. In defense, V. anguillarum utilizes O
      antigen polysaccharides to evade phagocytosis by the epithelial cells allowing it
      to colonize rapidly fish skin tissues.

PMID- 22662190
TI  - Genetic variation in functional traits influences arthropod community composition
      in aspen (Populus tremula L.).
AB  - We conducted a study of natural variation in functional leaf traits and herbivory
      in 116 clones of European aspen, Populus tremula L., the Swedish Aspen (SwAsp)
      collection, originating from ten degrees of latitude across Sweden and grown in a
      common garden. In surveys of phytophagous arthropods over two years, we found the
      aspen canopy supports nearly 100 morphospecies. We identified significant broad
      sense heritability of plant functional traits, basic plant defence chemistry, and
      arthropod community traits. The majority of arthropods were specialists, those
      coevolved with P. tremula to tolerate and even utilize leaf defence compounds.
      Arthropod abundance and richness were more closely related to plant growth rates
      than general chemical defences and relationships were identified between the
      arthropod community and stem growth, leaf and petiole morphology, anthocyanins,
      and condensed tannins. Heritable genetic variation in plant traits in young aspen
      was found to structure arthropod community; however no single trait drives the
      preferences of arthropod folivores among young aspen genotypes. The influence of
      natural variation in plant traits on the arthropod community indicates the
      importance of maintaining genetic variation in wild trees as keystone species for
      biodiversity. It further suggests that aspen can be a resource for the study of
      mechanisms of natural resistance to herbivores.

PMID- 22662191
TI  - Host plant use by competing acacia-ants: mutualists monopolize while parasites
      share hosts.
AB  - Protective ant-plant mutualisms that are exploited by non-defending parasitic
      ants represent prominent model systems for ecology and evolutionary biology. The
      mutualist Pseudomyrmex ferrugineus is an obligate plant-ant and fully depends on
      acacias for nesting space and food. The parasite Pseudomyrmex gracilis
      facultatively nests on acacias and uses host-derived food rewards but also
      external food sources. Integrative analyses of genetic microsatellite data,
      cuticular hydrocarbons and behavioral assays showed that an individual acacia
      might be inhabited by the workers of several P. gracilis queens, whereas one P.
      ferrugineus colony monopolizes one or more host trees. Despite these differences
      in social organization, neither of the species exhibited aggressive behavior
      among conspecific workers sharing a tree regardless of their relatedness. This
      lack of aggression corresponds to the high similarity of cuticular hydrocarbon
      profiles among ants living on the same tree. Host sharing by unrelated colonies,
      or the presence of several queens in a single colony are discussed as strategies
      by which parasite colonies could achieve the observed social organization. We
      argue that in ecological terms, the non-aggressive behavior of non-sibling P.
      gracilis workers--regardless of the route to achieve this social structure-
      enables this species to efficiently occupy and exploit a host plant. By contrast,
      single large and long-lived colonies of the mutualist P. ferrugineus monopolize
      individual host plants and defend them aggressively against invaders from other
      trees. Our findings highlight the necessity for using several methods in
      combination to fully understand how differing life history strategies affect
      social organization in ants.

PMID- 22662192
TI  - IQGAP1 interacts with components of the slit diaphragm complex in podocytes and
      is involved in podocyte migration and permeability in vitro.
AB  - IQGAP1 is a scaffold protein that interacts with proteins of the cytoskeleton and
      the intercellular adhesion complex. In podocytes, IQGAP1 is associated with
      nephrin in the glomerular slit diaphragm (SD) complex, but its role remains ill
      defined. In this work, we investigated the interaction of IQGAP1 with the
      cytoskeleton and SD proteins in podocytes in culture, and its role in podocyte
      migration and permeability. Expression, localization, and interactions between
      IQGAP1 and SD or cytoskeletal proteins were determined in cultured human
      podocytes by Western blot (WB), immunocytolocalization (IC), immunoprecipitation
      (IP), and In situ Proximity Ligation assay (IsPL). Involvement of IQGAP1 in
      migration and permeability was also assessed. IQGAP1 expression in normal kidney
      biopsies was studied by immunohistochemistry. IQGAP1 expression by podocytes
      increased during their in vitro differentiation. IC, IP, and IsPL experiments
      showed colocalizations and/or interactions between IQGAP1 and SD proteins
      (nephrin, MAGI-1, CD2AP, NCK 1/2, podocin), podocalyxin, and cytoskeletal
      proteins (alpha-actinin-4). IQGAP1 silencing decreased podocyte migration and
      increased the permeability of a podocyte layer. Immunohistochemistry on normal
      human kidney confirmed IQGAP1 expression in podocytes and distal tubular
      epithelial cells and also showed an expression in glomerular parietal epithelial
      cells. In summary, our results suggest that IQGAP1, through its interaction with
      components of SD and cytoskeletal proteins, is involved in podocyte barrier
      properties.

PMID- 22662193
TI  - Hepatitis C virus sensitizes host cells to TRAIL-induced apoptosis by up
      regulating DR4 and DR5 via a MEK1-dependent pathway.
AB  - BACKGROUND: Hepatitis C virus (HCV) is the leading cause of liver fibrosis,
      cirrhosis and hepatocellular carcinoma. It is believed that continuous liver cell
      apoptosis contributes to HCV pathogenesis. Recent studies have shown that HCV
      infection can sensitize host cells to TNF-related apoptosis-inducing ligand
      (TRAIL) induced apoptosis, but the mechanism by which HCV regulates the TRAIL
      pathway remains unclear. METHODS AND RESULTS: Using a sub-genomic replicon and
      full length virus, JFH-1, we demonstrate that HCV can sensitize host cells to
      TRAIL-induced apoptosis by up-regulating two TRAIL receptors, death receptor 4
      (DR4) and death receptor 5 (DR5). Furthermore, the HCV replicon enhanced
      transcription of DR5 via Sp1, and the HCV-mediated up-regulation of DR4 and DR5
      required MEK1 activity. HCV infection also stimulated the activity of MEK1, and
      the inhibition of MEK1 activity or the knockdown of MEK1 increased the
      replication of HCV. CONCLUSIONS: Our studies demonstrate that HCV replication
      sensitizes host cells to TRAIL-induced apoptosis by up-regulating DR4 and DR5 via
      a MEK1 dependent pathway. These findings may help to further understand the
      pathogenesis of HCV infection and provide a therapeutic target.

PMID- 22662194
TI  - Flexibility along the neck of the neogene terror bird Andalgalornis steulleti
      (Aves Phorusrhacidae).
AB  - BACKGROUND: Andalgalornis steulleti from the upper Miocene-lower Pliocene (~6
      million years ago) of Argentina is a medium-sized patagornithine phorusrhacid. It
      was a member of the predominantly South American radiation of 'terror birds'
      (Phorusrhacidae) that were apex predators throughout much of the Cenozoic. A
      previous biomechanical study suggests that the skull would be prepared to make
      sudden movements in the sagittal plane to subdue prey. METHODOLOGY/PRINCIPAL
      FINDINGS: We analyze the flexion patterns of the neck of Andalgalornis based on
      the neck vertebrae morphology and biometrics. The transitional cervical vertebrae
      5th and 9th clearly separate regions 1-2 and 2-3 respectively. Bifurcate neural
      spines are developed in the cervical vertebrae 7th to 12th suggesting the
      presence of a very intricate ligamentary system and of a very well developed
      epaxial musculature. The presence of the lig. elasticum interespinale is
      inferred. High neural spines of R3 suggest that this region concentrates the
      major stresses during downstrokes. CONCLUSIONS/SIGNIFICANCE: The musculoskeletal
      system of Andalgalornis seems to be prepared (1) to support a particularly big
      head during normal stance, and (2) to help the neck (and the head) rising after
      the maximum ventroflexion during a strike. The study herein is the first
      interpretation of the potential performance of the neck of Andalgalornis in its
      entirety and we considered this an important starting point to understand and
      reconstruct the flexion pattern of other phorusrhacids from which the neck is
      unknown.

PMID- 22662195
TI  - Gas7-deficient mouse reveals roles in motor function and muscle fiber composition
      during aging.
AB  - BACKGROUND: Growth arrest-specific gene 7 (Gas7) has previously been shown to be
      involved in neurite outgrowth in vitro; however, its actual role has yet to be
      determined. To investigate the physiological function of Gas7 in vivo, here we
      generated a Gas7-deficient mouse strain with a labile Gas7 mutant protein whose
      functions are similar to wild-type Gas7. METHODOLOGY/PRINCIPAL FINDINGS: Our data
      show that aged Gas7-deficient mice have motor activity defects due to decreases
      in the number of spinal motor neurons and in muscle strength, of which the latter
      may be caused by changes in muscle fiber composition as shown in the soleus. In
      cross sections of the soleus of Gas7-deficient mice, gross morphological features
      and levels of myosin heavy chain I (MHC I) and MHC II markers revealed
      significantly fewer fast fibers. In addition, we found that nerve terminal
      sprouting, which may be associated with slow and fast muscle fiber composition,
      was considerably reduced at neuromuscular junctions (NMJ) during aging.
      CONCLUSIONS/SIGNIFICANCE: These findings indicate that Gas7 is involved in motor
      neuron function associated with muscle strength maintenance.

PMID- 22662196
TI  - Identification and comparative expression analysis of interleukin 2/15 receptor
      beta chain in chickens infected with E. tenella.
AB  - BACKGROUND: Interleukin (IL) 2 and IL15 receptor beta chain (IL2/15Rbeta, CD122)
      play critical roles in signal transduction for the biological activities of IL2
      and IL15. Increased knowledge of non-mammalian IL2/15Rbeta will enhance the
      understanding of IL2 and IL15 functions. METHODOLOGY/PRINCIPAL FINDINGS:
      [corrected] Chicken IL2/15Rbeta (chIL2/15Rbeta) cDNA was cloned using 5'/3'-RACE.
      The predicted protein sequence contained 576 amino acids and typical features of
      the type-I cytokine receptor family. COS-7 cells transfected with chIL2/15Rbeta
      produced proteins of approximately 75 and 62.5 kDa under normal and tunicamycin
      treated conditions, respectively. The genomic structure of chIL2/15Rbeta was
      similar to its mammalian counterparts. chIL2/15Rbeta transcripts were detected in
      the lymphoblast cell line CU205 and in normal lymphoid organs and at moderate
      levels in bursa samples. Expression profiles of chIL2/15Rbeta and its related
      cytokines and receptors were examined in ConA-stimulated splenic lymphocytes and
      in ceca-tonsils of Eimeria tenella-infected chickens using quantitative real-time
      PCR. Expression levels of chIL2/15Rbeta, chIL2Ralpha, and chIL15Ralpha were
      generally elevated in ceca-tonsils and ConA-activated splenic lymphocytes.
      However, chIL2 and chIL15 expression levels were differentially regulated between
      the samples. chIL2 expression was upregulated in ConA-activated splenic
      lymphocytes, but not in ceca-tonsils. In constrast, chIL15 expression was
      upregulated in ceca-tonsils, but not in ConA-activated splenic lymphocytes.
      CONCLUSIONS/SIGNIFICANCE: We identified an avian form of IL2/15Rbeta and compared
      its gene expression pattern with those of chIL2, chIL15, chIL2Ralpha, and
      chIL15Ralpha. Our observations suggest that chIL15 and its receptors, including
      chIL2/15Rbeta, play important roles in mucosal immunity to intestinal
      intracellular parasites such as Eimeria.

PMID- 22662197
TI  - Enhancer of zeste homolog 2 induces pulmonary artery smooth muscle cell
      proliferation.
AB  - INTRODUCTION: Pulmonary Arterial Hypertension (PAH) is a progressively
      devastating disease characterized by excessive proliferation of the Pulmonary
      Arterial Smooth Muscle Cells (PASMCs). Studies suggest that PAH and cancers share
      an apoptosis-resistant state featuring excessive cell proliferation. The
      proliferation of cancer cells is mediated by increased expression of Enhancer of
      Zeste Homolog 2 (EZH2), a mammalian histone methyltransferase that contributes to
      the epigenetic silencing of target genes. However, the role of EZH2 in PAH has
      not been studied. In this study, it is hypothesized that EZH2 could play a role
      in the proliferation of PASMCs. METHODS: In the present study, the expression
      patterns of EZH2 were investigated in normal and hypertensive mouse PASMCs. The
      effects of EZH2 overexpression on the proliferation of human PASMCs were tested.
      PASMCs were transfected with EZH2 or GFP using nucleofector system. After
      transfection, the cells were incubated for 48 hours at 37 degrees C.
      Proliferation and cell cycle analysis were performed using flow cytometry.
      Apoptosis of PASMCs was determined using annexin V staining and cell migration
      was tested by wound healing assay. RESULTS: EZH2 protein expression in mouse
      PASMCs were correlated with an increase in right ventricular systolic pressure
      and Right Ventricular Hypertrophy (RVH). The overexpression of EZH2 in human
      PASMCs enhances proliferation, migration, and decrease in the rate of apoptosis
      when compared to GFP-transfected cells. In the G2/M phase of the EZH2 transfected
      cells, there was a 3.5 fold increase in proliferation, while there was a
      significant decrease in the rate of apoptosis of PASMCs, when compared to
      control. CONCLUSION: These findings suggest that EZH2 plays a role in the
      migration and proliferation of PASMCs, which is a major hallmark in PAH. It also
      suggests that EZH2 could play a role in the development of PAH and can serve as a
      potential target for new therapies for PAH.

PMID- 22662198
TI  - Identification and function of exchange proteins activated directly by cyclic AMP
      (Epac) in mammalian spermatozoa.
AB  - The role of cAMP in spermatic functions was classically thought to be mediated
      exclusively through the activation of Protein Kinase A (PKA). However, it has
      recently been shown that cAMP also exerts its effects through a PKA-independent
      pathway activating a family of proteins known as Epac proteins. Therefore, many
      of the spermatic functions thought to be regulated by cAMP through the activation
      of PKA are again under study. We aimed to identify and to investigate the role of
      Epac proteins in spermatozoa using a specific permeable analog (8-Br-2'-O-Me
      cAMP). Also, we aimed to study its relationship with E-cadherin, an adhesion
      protein involved in fertility. Our results demonstrate the presence and sub
      cellular distribution of Epac 1 and Epac 2 in mammalian spermatozoa. Capacitation
      and the acrosome reaction induced a change in the localization of Epac proteins
      in sperm. Moreover, incubation with 8-Br-2'-O-Me-cAMP prompted an increase in
      Rap1 activation, in the scrambling of plasma membrane phospholipids (necessary
      for the capacitation process), the acrosome reaction, motility, and calcium
      mobilization, when spermatozoa were incubated in acrosome reaction conditions.
      Finally, the activation of Epac proteins induced a change in the distribution of
      E-cadherin. Therefore, the increase in the acrosome reaction, together with the
      increase in calcium (which is known to be essential for fertilization) and the
      Epac nteraction with E-cadherin, might indicate that Epac proteins have an
      important role in gamete recognition and fertilization.

PMID- 22662199
TI  - Nasal bone shape is under complex epistatic genetic control in mouse
      interspecific recombinant congenic strains.
AB  - BACKGROUND: Genetic determinism of cranial morphology in the mouse is still
      largely unknown, despite the localization of putative QTLs and the identification
      of genes associated with Mendelian skull malformations. To approach the
      dissection of this multigenic control, we have used a set of interspecific
      recombinant congenic strains (IRCS) produced between C57BL/6 and mice of the
      distant species Mus spretus (SEG/Pas). Each strain has inherited 1.3% of its
      genome from SEG/Pas under the form of few, small-sized, chromosomal segments.
      RESULTS: The shape of the nasal bone was studied using outline analysis combined
      with Fourier descriptors, and differential features were identified between IRCS
      BcG-66H and C57BL/6. An F2 cross between BcG-66H and C57BL/6 revealed that, out
      of the three SEG/Pas-derived chromosomal regions present in BcG-66H, two were
      involved. Segments on chromosomes 1 (~32 Mb) and 18 (~13 Mb) showed additive
      effect on nasal bone shape. The three chromosomal regions present in BcG-66H were
      isolated in congenic strains to study their individual effect. Epistatic
      interactions were assessed in bicongenic strains. CONCLUSIONS: Our results show
      that, besides a strong individual effect, the QTL on chromosome 1 interacts with
      genes on chromosomes 13 and 18. This study demonstrates that nasal bone shape is
      under complex genetic control but can be efficiently dissected in the mouse using
      appropriate genetic tools and shape descriptors.

PMID- 22662200
TI  - Pan-pathway based interaction profiling of FDA-approved nucleoside and nucleobase
      analogs with enzymes of the human nucleotide metabolism.
AB  - To identify interactions a nucleoside analog library (NAL) consisting of 45 FDA
      approved nucleoside analogs was screened against 23 enzymes of the human
      nucleotide metabolism using a thermal shift assay. The method was validated with
      deoxycytidine kinase; eight interactions known from the literature were detected
      and five additional interactions were revealed after the addition of ATP, the
      second substrate. The NAL screening gave relatively few significant hits,
      supporting a low rate of "off target effects." However, unexpected ligands were
      identified for two catabolic enzymes guanine deaminase (GDA) and uridine
      phosphorylase 1 (UPP1). An acyclic guanosine prodrug analog, valaciclovir, was
      shown to stabilize GDA to the same degree as the natural substrate, guanine, with
      a DeltaT(agg) around 7 degrees C. Aciclovir, penciclovir, ganciclovir,
      thioguanine and mercaptopurine were also identified as ligands for GDA. The
      crystal structure of GDA with valaciclovir bound in the active site was
      determined, revealing the binding of the long unbranched chain of valaciclovir in
      the active site of the enzyme. Several ligands were identified for UPP1:
      vidarabine, an antiviral nucleoside analog, as well as trifluridine, idoxuridine,
      floxuridine, zidovudine, telbivudine, fluorouracil and thioguanine caused
      concentration-dependent stabilization of UPP1. A kinetic study of UPP1 with
      vidarabine revealed that vidarabine was a mixed-type competitive inhibitor with
      the natural substrate uridine. The unexpected ligands identified for UPP1 and GDA
      imply further metabolic consequences for these nucleoside analogs, which could
      also serve as a starting point for future drug design.

PMID- 22662201
TI  - Ulcerative colitis impairs the acylethanolamide-based anti-inflammatory system
      reversal by 5-aminosalicylic acid and glucocorticoids.
AB  - Studies in animal models and humans suggest anti-inflammatory roles on the N
      acylethanolamide (NAE)-peroxisome proliferators activated receptor alpha
      (PPARalpha) system in inflammatory bowel diseases. However, the presence and
      function of NAE-PPARalpha signaling system in the ulcerative colitis (UC) of
      humans remain unknown as well as its response to active anti-inflammatory
      therapies such as 5-aminosalicylic acid (5-ASA) and glucocorticoids. Expression
      of PPARalpha receptor and PPARalpha ligands-biosynthetic (NAPE-PLD) and 
      degrading (FAAH and NAAA) enzymes were analyzed in untreated active and 5
      ASA/glucocorticoids/immunomodulators-treated quiescent UC patients compared to
      healthy human colonic tissue by RT-PCR and immunohistochemical analyses.
      PPARalpha, NAAA, NAPE-PLD and FAAH showed differential distributions in the
      colonic epithelium, lamina propria, smooth muscle and enteric plexus. Gene
      expression analysis indicated a decrease of PPARalpha, PPARgamma and NAAA, and an
      increase of FAAH and iNOS in the active colitis mucosa. Immunohistochemical
      expression in active colitis epithelium confirmed a PPARalpha decrease, but
      showed a sharp NAAA increase and a NAPE-PLD decrease, which were partially
      restored to control levels after treatment. We also characterized the immune
      cells of the UC mucosa infiltrate. We detected a decreased number of NAAA
      positive and an increased number of FAAH-positive immune cells in active UC,
      which were partially restored to control levels after treatment. NAE-PPARalpha
      signaling system is impaired during active UC and 5-ASA/glucocorticoids treatment
      restored its normal expression. Since 5-ASA actions may work through PPARalpha
      and glucocorticoids through NAE-producing/degrading enzymes, the use of PPARalpha
      agonists or FAAH/NAAA blockers that increases endogenous PPARalpha ligands may
      yield similar therapeutics advantages.

PMID- 22662202
TI  - Identification, expression and target gene analyses of Micrornas in Spodoptera
      litura.
AB  - MicroRNAs (miRNAs) are small RNAs widely present in animals and plants and
      involved in post-transcriptional regulation of gene transcripts. In this study we
      identified and validated 58 miRNAs from an EST dataset of Spodoptera litura based
      on the computational and experimental analysis of sequence conservation and
      secondary structure of miRNA by comparing the miRNA sequences in the miRbase. RT
      PCR was conducted to examine the expression of these miRNAs and stem-loop RT-PCR
      assay was performed to examine expression of 11 mature miRNAs (out of the 58
      putative miRNA) that showed significant changes in different tissues and stages
      of the insect development. One hundred twenty eight possible target genes against
      the 11 miRNAs were predicted by using computational methods. Binding of one miRNA
      (sli-miR-928b) with the three possible target mRNAs was confirmed by Southern
      blotting, implying its possible function in regulation of the target genes.

PMID- 22662203
TI  - Nilotinib counteracts P-glycoprotein-mediated multidrug resistance and synergizes
      the antitumoral effect of doxorubicin in soft tissue sarcomas.
AB  - The therapeutic effect of doxorubicin (DXR) in the treatment of soft tissue
      sarcomas (STS) is limited by its toxicity and the development of multidrug
      resistance (MDR), the latter mainly induced by high expression of efflux pumps
      (e.g., P-glycoprotein [P-gp]). Therefore, the search for alternative therapies,
      which sensitize these tumors to chemotherapy while maintaining a low toxicity
      profile, is a rational approach. We assessed efficacy and molecular mechanisms
      involved in the antiproliferative effects of the tyrosine kinase inhibitors,
      nilotinib and imatinib, as single agents or in combination with DXR, in human
      synovial sarcoma SW982 and leiomyosarcoma SK-UT-1 cells. As single compound
      nilotinib (1-10 uM) was more potent than imatinib inhibiting the growth of SK-UT
      1 and SW982 cells by 33.5-59.6%, respectively. Importantly, only nilotinib
      synergized the antitumoral effect of DXR (0.05-0.5 uM) by at least 2-fold, which
      clearly surpassed the mere sum of effects according to isobolographic analysis.
      Moreover, nilotinib in combination with DXR had a sustained effect on cell number
      (-70.3+/-5.8%) even 12 days after withdrawal of drugs compared to DXR alone. On
      the molecular level, only nilotinib fully blocked FBS-induced ERK1 and p38 MAPK
      activation, hence, reducing basal and DXR-induced up-regulation of P-gp levels.
      Moreover, efflux activity of the MDR-related proteins P-gp and MRP-1 was
      inhibited, altogether resulting in intracellular DXR retention. In high-risk STS
      tumors 53.8% and 15.4% were positive for P-gp and MRP-1 expression, respectively,
      with high incidence of P-gp in synovial sarcoma (72.7%). In summary, nilotinib
      exhibits antiproliferative effects on cellular models of STS and sensitizes them
      to DXR by reverting DXR-induced P-gp-mediated MDR and inhibiting MRP-1 activity,
      leading to a synergistic effect with potential for clinical treatment.

PMID- 22662204
TI  - Metabolic profiling of the protozoan parasite Entamoeba invadens revealed
      activation of unpredicted pathway during encystation.
AB  - Encystation, which is cellular differentiation from the motile, proliferative,
      labile trophozoite form to the dormant, resistant cyst form, is a crucial process
      found in parasitic and free-living protozoa such as Entamoeba, Giardia,
      Acanthamoeba, and Balamuthia. Since encystation is an essential process to deal
      with the adverse external environmental changes during the life cycle, and often
      integral to the transmission of the diseases, biochemical understanding of the
      process potentially provides useful measures against the infections caused by
      this group of protozoa. In this study, we investigated metabolic and
      transcriptomic changes that occur during encystation in Entamoeba invadens, the
      reptilian sibling of mammal-infecting E. histolytica, using capillary
      electrophoresis-tandem mass spectrometry-based metabolite profiling and DNA
      microarray-based expression profiling. As the encystation progressed, the levels
      of majority of metabolites involved in glycolysis and nucleotides drastically
      decreased, indicating energy generation is ceased. Furthermore, the flux of
      glycolysis was redirected toward chitin wall biosynthesis. We found remarkable
      temporal increases in biogenic amines such as isoamylamine, isobutylamine, and
      cadaverine, during the early period of encystation, when the trophozoites form
      large multicellular aggregates (precyst). We also found remarkable induction of
      gamma-aminobutyric acid (GABA) during encystation. This study has unveiled for
      the first time the dynamics of the transcriptional and metabolic regulatory
      networks during encystation, and should help in better understanding of the
      process in pathogenic eukaryotes, and further development of measures controlling
      infections they cause.

PMID- 22662205
TI  - Lobelia siphilitica plants that escape herbivory in time also have reduced latex
      production.
AB  - Flowering phenology is an important determinant of a plant's reproductive
      success. Both assortative mating and niche construction can result in the
      evolution of correlations between phenology and other reproductive, functional,
      and life history traits. Correlations between phenology and herbivore defence
      traits are particularly likely because the timing of flowering can allow a plant
      to escape herbivory. To test whether herbivore escape and defence are correlated,
      we estimated phenotypic and genetic correlations between flowering phenology and
      latex production in greenhouse-grown Lobelia siphilitica L. (Lobeliaceae).
      Lobelia siphilitica plants that flower later escape herbivory by a specialist pre
      dispersal seed predator, and thus should invest fewer resources in defence.
      Consistent with this prediction, we found that later flowering was phenotypically
      and genetically correlated with reduced latex production. To test whether
      herbivore escape and latex production were costly, we also measured four fitness
      correlates. Flowering phenology was negatively genetically correlated with three
      out of four fitness estimates, suggesting that herbivore escape can be costly. In
      contrast, we did not find evidence for costs of latex production. Generally, our
      results suggest that herbivore escape and defence traits will not evolve
      independently in L. siphilitica.

PMID- 22662206
TI  - Lipoxin A4 stimulates calcium-activated chloride currents and increases airway
      surface liquid height in normal and cystic fibrosis airway epithelia.
AB  - Cystic Fibrosis (CF) is a genetic disease characterised by a deficit in
      epithelial Cl(-) secretion which in the lung leads to airway dehydration and a
      reduced Airway Surface Liquid (ASL) height. The endogenous lipoxin LXA(4) is a
      member of the newly identified eicosanoids playing a key role in ending the
      inflammatory process. Levels of LXA(4) are reported to be decreased in the
      airways of patients with CF. We have previously shown that in normal human
      bronchial epithelial cells, LXA(4) produced a rapid and transient increase in
      intracellular Ca(2+). We have investigated, the effect of LXA(4) on Cl(-)
      secretion and the functional consequences on ASL generation in bronchial
      epithelial cells obtained from CF and non-CF patient biopsies and in bronchial
      epithelial cell lines. We found that LXA(4) stimulated a rapid intracellular
      Ca(2+) increase in all of the different CF bronchial epithelial cells tested. In
      non-CF and CF bronchial epithelia, LXA(4) stimulated whole-cell Cl(-) currents
      which were inhibited by NPPB (calcium-activated Cl(-) channel inhibitor), BAPTA
      AM (chelator of intracellular Ca(2+)) but not by CFTRinh-172 (CFTR inhibitor). We
      found, using confocal imaging, that LXA(4) increased the ASL height in non-CF and
      in CF airway bronchial epithelia. The LXA(4) effect on ASL height was sensitive
      to bumetanide, an inhibitor of transepithelial Cl(-) secretion. The LXA(4)
      stimulation of intracellular Ca(2+), whole-cell Cl(-) currents, conductances and
      ASL height were inhibited by Boc-2, a specific antagonist of the ALX/FPR2
      receptor. Our results provide, for the first time, evidence for a novel role of
      LXA(4) in the stimulation of intracellular Ca(2+) signalling leading to Ca(2+)
      activated Cl(-) secretion and enhanced ASL height in non-CF and CF bronchial
      epithelia.

PMID- 22662207
TI  - Mechanism underlying defective interferon gamma-induced IDO expression in non
      obese diabetic mouse fibroblasts.
AB  - Indoleamine 2,3-dioxygenase (IDO) can locally suppress T cell-mediated immune
      responses. It has been shown that defective self-tolerance in early prediabetic
      female non-obese diabetic (NOD) mice can be attributed to the impaired interferon
      gamma (IFN-gamma)- induced IDO expression in dendritic cells of these animals. As
      IFN-gamma can induce IDO in both dendritic cells and fibroblasts, we asked the
      question of whether there exists a similar defect in IFN-gamma-induced IDO
      expression in NOD mice dermal fibroblasts. To this end, we examined the effect of
      IFN-gamma on expression of IDO and its enzymatic activity in NOD dermal
      fibroblasts. The results showed that fibroblasts from either prediabetic (8 wks
      of age) female or male, and diabetic female or male (12 and 24 wks of age
      respectively) NOD mice failed to express IDO in response to IFN-gamma treatment.
      To find underlying mechanisms, we scrutinized the IFN- gamma signaling pathway
      and investigated expression of other IFN-gamma-modulated factors including major
      histocompatibility complex class I (MHC-I) and type I collagen (COL-I). The
      findings revealed a defect of signal transducer and activator of transcription 1
      (STAT1) phosphorylation in NOD cells relative to that of controls. Furthermore,
      we found an increase in MHC-I and suppression of COL-I expression in fibroblasts
      from both NOD and control mice following IFN-gamma treatment; indicating that the
      impaired response to IFN-gamma in NOD fibroblasts is specific to IDO gene.
      Finally, we showed that an IFN-gamma-independent IDO expression pathway i.e.
      lipopolysaccharide (LPS)-mediated-c-Jun kinase is operative in NOD mice
      fibroblast. In conclusion, the findings of this study for the first time indicate
      that IFN-gamma fails to induce IDO expression in NOD dermal fibroblasts; this may
      partially be due to defective STAT1 phosphorylation in IFN-gamma-induced-IDO
      signaling pathway.

PMID- 22662208
TI  - Bioactive dietary supplements reactivate ER expression in ER-negative breast
      cancer cells by active chromatin modifications.
AB  - Breast cancer is the most common cancer and the leading cause of cancer death in
      women. Although tamoxifen therapy is successful for some patients, it does not
      provide adequate benefit for those who have estrogen receptor (ER)-negative
      cancers. Therefore, we approached novel treatment strategies by combining two
      potential bioactive dietary supplements for the reactivation of ERalpha
      expression for effective treatment of ERalpha-negative breast cancer with
      tamoxifen. Bioactive dietary supplements such as green tea polyphenols (GTPs) and
      sulforaphane (SFN) inhibit DNA methyltransferases (DNMTs) and histone
      deacetylases (HDACs), respectively, which are of central importance to cancer
      prevention. In the present study, we have observed that treatment of ERalpha
      negative breast cancer cells with GTPs and SFN alone or in combination leads to
      the reactivation of ERalpha expression. The combination of 20 ug/mL GTPs and 5 uM
      SFN was found to be the optimal dose of ERalpha-reactivation at 3 days in MDA-MB
      231 cells. The reactivation of ERalpha expression was consistently correlated
      with ERalpha promoter hypomethylation and hyperacetylation. Chromatin
      immunoprecipitation (ChIP) analysis of the ERalpha promoter revealed that GTPs
      and SFN altered the binding of ERalpha-transcriptional co-repressor complex
      thereby contributing to ERalpha-reactivation. In addition, treatment with
      tamoxifen in combination with GTPs and SFN significantly increased both cell
      death and inhibition of cellular proliferation in MDA-MB-231 cells in comparison
      to treatment with tamoxifen alone. Collectively, our findings suggest that a
      novel combination of bioactive-HDAC inhibitors with bioactive-demethylating
      agents is a promising strategy for the effective treatment of hormonal refractory
      breast cancer with available anti-estrogens.

PMID- 22662209
TI  - Angiotensin II activates the calcineurin/NFAT signaling pathway and induces
      cyclooxygenase-2 expression in rat endometrial stromal cells.
AB  - Cyclooxygenase (COX)-2, the inducible isoform of cyclooxygenase, plays a role in
      the process of uterine decidualization and blastocyst attachment. On the other
      hand, overexpression of COX-2 is involved in the proliferation of the endometrial
      tissue during endometriosis. Deregulation of the renin-angiotensin-system plays a
      role in the pathophysiology of endometriosis and pre-eclampsia. Angiotensin II
      increases intracellular Ca(2+) concentration by targeting phospholypase C-gamma
      in endometrial stromal cells (ESC). A key element of the cellular response to
      Ca(2+) signals is the activity of the Ca(2+)- and calmodulin-dependent
      phosphatase calcineurin. Our first aim was to study whether angiotensin II
      stimulated Cox-2 gene expression in rat ESC and to analyze whether calcineurin
      activity was involved. In cells isolated from non-pregnant uteri, COX-2
      expression--both mRNA and protein--was induced by co-stimulation with phorbol
      ester and calcium ionophore (PIo), as well as by angiotensin II. Pretreatment
      with the calcineurin inhibitor cyclosporin A inhibited this induction. We further
      analyzed the role of the calcineurin/NFAT signaling pathway in the induction of
      Cox-2 gene expression in non-pregnant rat ESC. Cyclosporin A abolished NFATc1
      dephosphorylation and translocation to the nucleus. Cyclosporin A also inhibited
      the transcriptional activity driven by the Cox-2 promoter. Exogenous expression
      of the peptide VIVIT -specific inhibitor of calcineurin/NFAT binding- blocked the
      activation of Cox-2 promoter and the up-regulation of COX-2 protein in these
      cells. Finally we analyzed Cox-2 gene expression in ESC of early-pregnant rats.
      COX-2 expression--both mRNA and protein--was induced by stimulation with PIo as
      well as by angiotensin II. This induction appears to be calcineurin independent,
      since it was not abrogated by cyclosporin A. In conclusion, angiotensin II
      induced Cox-2 gene expression by activating the calcineurin/NFAT signaling
      pathway in endometrial stromal cells of non-pregnant but not of early-pregnant
      rats. These results might be related to differential roles that COX-2 plays in
      the endometrium.

PMID- 22662210
TI  - Low dose vaccination with attenuated Francisella tularensis strain SchuS4 mutants
      protects against tularemia independent of the route of vaccination.
AB  - Tularemia, caused by the gram-negative bacterium Francisella tularensis, is a
      severe, sometimes fatal disease. Interest in tularemia has increased over the
      last decade due to its history as a biological weapon. In particular, development
      of novel vaccines directed at protecting against pneumonic tularemia has been an
      important goal. Previous work has demonstrated that, when delivered at very high
      inoculums, administration of live, highly attenuated strains of virulent F.
      tularensis can protect against tularemia. However, lower vaccinating inoculums
      did not offer similar immunity. One concern of using live vaccines is that the
      host may develop mild tularemia in response to infection and use of high
      inoculums may contribute to this issue. Thus, generation of a live vaccine that
      can efficiently protect against tularemia when delivered in low numbers, e.g.
      <100 organisms, may address this concern. Herein we describe the ability of three
      defined, attenuated mutants of F. tularensis SchuS4, deleted for FTT0369c,
      FTT1676, or FTT0369c and FTT1676, respectively, to engender protective immunity
      against tularemia when delivered at concentrations of approximately 50 or fewer
      bacteria. Attenuated strains for use as vaccines were selected by their inability
      to efficiently replicate in macrophages in vitro and impaired replication and
      dissemination in vivo. Although all strains were defective for replication in
      vitro within macrophages, protective efficacy of each attenuated mutant was
      correlated with their ability to modestly replicate and disseminate in the host.
      Finally, we demonstrate the parenteral vaccination with these strains offered
      superior protection against pneumonic tularemia than intranasal vaccination.
      Together our data provides proof of principle that low dose attenuated vaccines
      may be a viable goal in development of novel vaccines directed against tularemia.

PMID- 22662211
TI  - NMDA receptors in GABAergic synapses during postnatal development.
AB  - GABA (gamma-aminobutyric-acid), the main inhibitory neurotransmitter in the adult
      brain, exerts depolarizing (excitatory) actions during development and this
      GABAergic depolarization cooperates with NMDARs (N-methyl-D-aspartate receptors)
      to drive spontaneous synchronous activity (SSA) that is fundamentally important
      for developing neuronal networks. Although GABAergic depolarization is known to
      assist in the activation of NMDARs during development, the subcellular
      localization of NMDARs relative to GABAergic synapses is still unknown. Here, we
      investigated the subcellular distribution of NMDARs in association with GABAergic
      synapses at the developmental stage when SSA is most prominent in mice. Using
      multiple immunofluorescent labeling and confocal laser-scanning microscopy in the
      developing mouse hippocampus, we found that NMDARs were associated with both
      glutamatergic and GABAergic synapses at postnatal day 6-7 and we observed a
      direct colocalization of GABA(A)- and NMDA-receptor labeling in GABAergic
      synapses. Electron microscopy of pre-embedding immunogold-immunoperoxidase
      reactions confirmed that GluN1, GluN2A and GluN2B NMDAR subunits were all
      expressed in glutamatergic and GABAergic synapses postsynaptically. Finally,
      quantitative post-embedding immunogold labeling revealed that the density of
      NMDARs was 3 times higher in glutamatergic than in GABAergic synapses. Since
      GABAergic synapses were larger, there was little difference in the total number
      of NMDA receptors in the two types of synapses. In addition, receptor density in
      synapses was substantially higher than extrasynaptically. These data can provide
      the neuroanatomical basis of a new interpretation of previous physiological data
      regarding the GABA(A)R-NMDAR cooperation during early development. We suggest
      that during SSA, synaptic GABA(A)R-mediated depolarization assists NMDAR
      activation right inside GABAergic synapses and this effective spatial cooperation
      of receptors and local change of membrane potential will reach developing
      glutamatergic synapses with a higher probability and efficiency even further away
      on the dendrites. This additional level of cooperation that operates within the
      depolarizing GABAergic synapse, may also allow its own modification triggered by
      Ca(2+)-influx through the NMDA receptors.

PMID- 22662212
TI  - Dynamic contrast-enhanced MRI assessment of hyperemic fractional microvascular
      blood plasma volume in peripheral arterial disease: initial findings.
AB  - OBJECTIVES: The aim of the current study was to describe a method that assesses
      the hyperemic microvascular blood plasma volume of the calf musculature. The
      reversibly albumin binding contrast agent gadofosveset was used in dynamic
      contrast-enhanced magnetic resonance imaging (DCE MRI) to assess the
      microvascular status in patients with peripheral arterial disease (PAD) and
      healthy controls. In addition, the reproducibility of this method in healthy
      controls was determined. MATERIALS AND METHODS: Ten PAD patients with
      intermittent claudication and 10 healthy control subjects were included. Patients
      underwent contrast-enhanced MR angiography of the peripheral arteries, followed
      by one DCE MRI examination of the musculature of the calf. Healthy control
      subjects were examined twice on different days to determine normative values and
      the interreader and interscan reproducibility of the technique. The MRI protocol
      comprised dynamic imaging of contrast agent wash-in under reactive hyperemia
      conditions of the calf musculature. Using pharmacokinetic modeling the hyperemic
      fractional microvascular blood plasma volume (V(p), unit: %) of the anterior
      tibial, gastrocnemius and soleus muscles was calculated. RESULTS: V(p) was
      significantly lower for all muscle groups in PAD patients (4.3+/-1.6%, 5.0+/-3.3%
      and 6.1+/-3.6% for anterior tibial, gastrocnemius and soleus muscles,
      respectively) compared to healthy control subjects (9.1+/-2.0%, 8.9+/-1.9% and
      9.3+/-2.1%). Differences in V(p) between muscle groups were not significant. The
      coefficient of variation of V(p) varied from 10-14% and 11-16% at interscan and
      interreader level, respectively. CONCLUSIONS: Using DCE MRI after contrast
      enhanced MR angiography with gadofosveset enables reproducible assessment of
      hyperemic fractional microvascular blood plasma volume of the calf musculature.
      V(p) was lower in PAD patients than in healthy controls, which reflects a
      promising functional (hemodynamic) biomarker for the microvascular impairment of
      macrovascular lesions.

PMID- 22662213
TI  - p21 as a transcriptional co-repressor of S-phase and mitotic control genes.
AB  - It has been previously described that p21 functions not only as a CDK inhibitor
      but also as a transcriptional co-repressor in some systems. To investigate the
      roles of p21 in transcriptional control, we studied the gene expression changes
      in two human cell systems. Using a human leukemia cell line (K562) with inducible
      p21 expression and human primary keratinocytes with adenoviral-mediated p21
      expression, we carried out microarray-based gene expression profiling. We found
      that p21 rapidly and strongly repressed the mRNA levels of a number of genes
      involved in cell cycle and mitosis. One of the most strongly down-regulated genes
      was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N
      terminal region of p21 is required for repression of gene expression of CCNE2 and
      other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to
      human CCNE2 and other p21-repressed genes gene in the vicinity of the
      transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase
      constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is
      present in most of the promoters of the p21-regulated genes. Altogether, the
      results suggest that p21 exerts a repressive effect on a relevant number of genes
      controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle
      progression would be mediated not only by the inhibition of CDKs but also by the
      transcriptional down-regulation of key genes.

PMID- 22662214
TI  - Proteinuria is associated with quality of life and depression in adults with
      primary glomerulopathy and preserved renal function.
AB  - BACKGROUND: There is no information about HRQoL, depression and associated
      factors in adult with nephrotic syndrome-associated glomerulopathy.
      METHODOLOGY/PRINCIPAL FINDINGS: Patients with primary glomerulopathy where
      compared with age and sex-matched hemodialysis patients and healthy subjects.
      Laboratory data, medical history, comorbid conditions were collected to evaluate
      factors associated with HRQoL (SF-36) and Depression (Hamilton Depression Rating
      Scale-HAMD). Glomerulopathy patients had low HRQoL in all eight SF-36 domains and
      two composite scores (physical and mental) in comparison with healthy subjects.
      HAMD score also was elevated and there was high depression prevalence. Overall,
      these data were comparable between glomerulopathy and hemodialysis patients.
      Using multiple regression analysis, factors associated with low HRQoL physical
      composite score were: last 24 h-urine protein excretion (-0.183, 95%CI -0.223 to 
      0.710 for each gram of proteinuria, p = 0.01) and cyclosporine use (-15.315,
      95%CI -25.913 to -2.717, p = 0.03). Low HRQoL mental composite score was
      associated with last 24 h-urine protein excretion (-0.157, 95%CI -0.278 to -0.310
      for each gram of proteinuria, p = 0.03) and HMAD score was independently
      associated with age (0.155, 95%CI 0.318 to 0.988 for each year, p = 0.04), female
      sex (4.788, 95%CI 1.005 to 8.620, 0 = 0.03), disease duration (0.074, 95%CI 0.021
      to 0.128 for each month, p = 0.01) and last 24 h-urine protein excretion (0.050,
      95%CI 0.018 to 0.085 for each gram of proteinuria, p = 0.02).
      CONCLUSIONS/SIGNIFICANCE: Nephrotic-syndrome associated glomerulopathy patients
      have low HRQoL and high prevalence of depression symptoms, comparable with those
      of hemodialysis patients. Last 24 h-protein excretion rate is independently
      associated with physical and mental HRQoL domains in addition to depression.

PMID- 22662215
TI  - EMT and stem cell-like properties associated with HIF-2alpha are involved in
      arsenite-induced transformation of human bronchial epithelial cells.
AB  - BACKGROUND: Arsenic is well-established as a human carcinogen, but the molecular
      mechanisms leading to arsenic-induced carcinogenesis are complex and elusive. It
      is not been determined if the epithelial-mesenchymal transition (EMT) and stem
      cell-like properties contribute in causing to carcinogen-induced malignant
      transformation and subsequent tumor formation. METHODS: To investigate the
      molecular mechanisms underlying EMT and the emergence of cancer stem cell-like
      properties during neoplastic transformation of human bronchial epithelial (HBE)
      cells induced by chronic exposure to arsenite. HBE cells were continuously
      exposed to arsenite. Spheroid formation assays and analyses of side populations
      (SPs) were performed to confirm that arsenite induces the acquired EMT and cancer
      stem cell-like phenotype. Treated HBE cells were molecularly characterized by RT
      PCR, Western blots, immunofluorescence, Southwestern assays, reporter assays, and
      chromatin immunoprecipitation. RESULTS: With chronic exposure to arsenite, HBE
      cells undergo an EMT and then acquire a malignant cancer stem cell-like
      phenotype. Twist1 and Bmi1 are involved in arsenite-induced EMT. The process is
      directly regulated by HIF-2alpha. The self-renewal genes, Oct4, Bmi1, and ALDH1,
      are necessary for arsenite-mediated maintenance of stem cells. CONCLUSIONS: EMT,
      regulated by HIF-2alpha, and the development of a cancer stem cell-like phenotype
      are associated with arsenite-induced transformation of HBE cells.

PMID- 22662217
TI  - Simple, rapid and cost-effective method for high quality nucleic acids extraction
      from different strains of Botryococcus braunii.
AB  - This study deals with an effective nucleic acids extraction method from various
      strains of Botryococcus braunii which possesses an extensive extracellular
      matrix. A method combining freeze/thaw and bead-beating with heterogeneous
      diameter of silica/zirconia beads was optimized to isolate DNA and RNA from
      microalgae, especially from B. braunii. Eukaryotic Microalgal Nucleic Acids
      Extraction (EMNE) method developed in this study showed at least 300 times higher
      DNA yield in all strains of B. braunii with high integrity and 50 times reduced
      working volume compared to commercially available DNA extraction kits. High
      quality RNA was also extracted using this method and more than two times the
      yield compared to existing methods. Real-time experiments confirmed the quality
      and quantity of the input DNA and RNA extracted using EMNE method. The method was
      also applied to other eukaryotic microalgae, such as diatoms, Chlamydomonas sp.,
      Chlorella sp., and Scenedesmus sp. resulting in higher efficiencies. Cost
      effectiveness analysis of DNA extraction by various methods revealed that EMNE
      method was superior to commercial kits and other reported methods by >15%. This
      method would immensely contribute to area of microalgal genomics.

PMID- 22662216
TI  - Proteomic analysis of Rta2p-dependent raft-association of detergent-resistant
      membranes in Candida albicans.
AB  - In Candida albicans, lipid rafts (also called detergent-resistant membranes,
      DRMs) are involved in many cellular processes and contain many important
      proteins. In our previous study, we demonstrated that Rta2p was required for
      calcineurin-mediated azole resistance and sphingoid long-chain base release in C.
      albicans. Here, we found that Rta2p was co-localized with raft-constituted
      ergosterol on the plasma membrane of C. albicans. Furthermore, this membrane
      expression pattern was totally disturbed by inhibitors of either ergosterol or
      sphingolipid synthesis. Biochemical fractionation of DRMs together with
      immunoblot uncovered that Rta2p, along with well-known DRM-associated proteins
      (Pma1p and Gas1p homologue), was associated with DRMs and their associations were
      blocked by inhibitors of either ergosterol or sphingolipid synthesis. Finally, we
      used the proteomic analysis together with immunoblot and identified that Rta2p
      was required for the association of 10 proteins with DRMs. These 5 proteins
      (Pma1p, Gas1p homologue, Erg11p, Pmt2p and Ali1p) have been reported to be DRM
      associated and also that Erg11p is a well-known target of azoles in C. albicans.
      In conclusion, our results showed that Rta2p was predominantly localized in lipid
      rafts and was required for the association of certain membrane proteins with
      lipid rafts in C. albicans.

PMID- 22662218
TI  - Hyaluronan binding motifs of USP17 and SDS3 exhibit anti-tumor activity.
AB  - BACKGROUND: We previously reported that the USP17 deubiquitinating enzyme having
      hyaluronan binding motifs (HABMs) interacts with human SDS3 (suppressor of
      defective silencing 3) and specifically deubiquitinates Lys-63 branched
      polyubiquitination of SDS3 resulting in negative regulation of histone
      deacetylase (HDAC) activity in cancer cells. Furthermore, USP17 and SDS3 mutually
      interact with each other to block cell proliferation in HeLa cells but the
      mechanism for this inhibition in cell proliferation is not known. We wished to
      investigate whether the HABMs of USP17 were responsible for tumor suppression
      activity. METHODOLOGY/PRINCIPAL FINDINGS: Similarly to USP17, we have identified
      that SDS3 also has three consecutive HABMs and shows direct binding with
      hyaluronan (HA) using cetylpyridinium chloride (CPC) assay. Additionally, HA
      oligosaccharides (6-18 sugar units) competitively block binding of endogenous HA
      polymer to HA binding proteins. Thus, administration of HA oligosaccharides
      antagonizes the interaction between HA and USP17 or SDS3. Interestingly, HABMs
      deleted USP17 showed lesser interaction with SDS3 but retain its deubiquitinating
      activity towards SDS3. The deletion of HABMs of USP17 could not alter its
      functional regulation on SDS3-associated HDAC activity. Furthermore, to explore
      whether HABMs in USP17 and SDS3 are responsible for the inhibition of cell
      proliferation, we investigated the effect of USP17 and SDS3-lacking HABMs on cell
      proliferation by soft agar, apoptosis, cell migration and cell proliferation
      assays. CONCLUSIONS: Our results have demonstrated that these HABMs in USP17 and
      its substrate SDS3 are mainly involved in the inhibition of anchorage-independent
      tumor growth.

PMID- 22662219
TI  - p53 modulation as a therapeutic strategy in gastrointestinal stromal tumors.
AB  - The KIT-inhibitor imatinib mesylate (IM) has greatly improved the treatment of
      metastatic gastrointestinal stromal tumors (GIST). IM exhibits strong
      antiproliferative effects but fails to induce sufficient levels of apoptosis
      resulting in low pathologic complete remission rates and a high rate of secondary
      progression in the metastatic setting. Upregulation of p53 by MDM2 inhibitors has
      been shown to induce apoptosis in p53 wildtype tumors. Analyzing a series of 62
      mostly untreated, localized and metastatic GIST we detected a low rate (3%) of
      inactivating p53 mutations, thus providing a rationale for further exploration of
      p53-directed therapeutic strategies. To this end, we studied nutlin-3, an
      inhibitor of the p53 antagonist MDM2, and RITA, a putative p53 activator, in GIST
      cell lines. Nutlin-3 effectively induced p53 at therapeutically relevant levels,
      which resulted in moderate antiproliferative effects and cell cycle arrest in p53
      wildtype GIST cell lines GIST430, GIST48 and GIST48B. P53 reactivation
      substantially improved the apoptotic response after effective KIT inhibition with
      sunitinib and 17-AAG in IM-resistant cell lines. The commonly used imatinib
      sensitive cell lines GIST882 and GIST-T1 were shown to harbor defective p53 and
      therefore failed to respond to nutlin-3 treatment. RITA induced p53 in GIST48B,
      followed by antiproliferative effects and a strong induction of apoptosis.
      Surprisingly, GIST-T1 was also highly sensitive to RITA despite lacking
      functional p53. This suggested a more complex, p53-independent mechanism of
      action for the latter compound. No antagonistic effects from p53-activating drugs
      were seen with any drug combination. Our data provide first evidence that
      modulation of the MDM2/p53 pathway may be therapeutically useful to improve the
      apoptotic response of KIT-inhibitory drugs in the treatment of naive GIST, with
      p53 mutation status being a predictive factor of response.

PMID- 22662220
TI  - Chlamydia trachomatis incidence and re-infection among young women--behavioural
      and microbiological characteristics.
AB  - BACKGROUND: This study aimed to estimate rates of chlamydia incidence and re
      infection and to investigate the dynamics of chlamydia organism load in
      prevalent, incident and re-infections among young Australian women. METHODS:
      1,116 women aged 16 to 25 years were recruited from primary care clinics in
      Australia. Vaginal swabs were collected at 3 to 6 month intervals for chlamydia
      testing. Chlamydia organism load was measured by quantitative PCR. RESULTS: There
      were 47 incident cases of chlamydia diagnosed and 1,056.34 person years of follow
      up with a rate of 4.4 per 100 person years (95% CI: 3.3, 5.9). Incident infection
      was associated with being aged 16 to 20 years [RR = 3.7 (95%CI: 1.9, 7.1)], being
      employed [RR = 2.4 (95%CI: 1.1, 4.9)] and having two or more new sex partners [RR
      = 5.5 (95%CI: 2.6, 11.7)]. Recent antibiotic use was associated with a reduced
      incidence [RR:0.1 (95%CI: 0.0, 0.5)]. There were 14 re-infections with a rate of
      22.3 per 100 person years (95%CI: 13.2, 37.6). The median time to re-infection
      was 4.6 months. Organism load was higher for prevalent than incident infections
      (p<0.01) and for prevalent than re-infections (p<0.01). CONCLUSIONS: Chlamydia is
      common among young women and a high proportion of women are re-infected within a
      short period of time, highlighting the need for effective partner treatment and
      repeat testing. The difference in organism load between prevalent and incident
      infections suggests prevalent infection may be more important for ongoing
      transmission of chlamydia.

PMID- 22662221
TI  - A metabolomic approach to the study of wine micro-oxygenation.
AB  - Wine micro-oxygenation is a globally used treatment and its effects were studied
      here by analysing by untargeted LC-MS the wine metabolomic fingerprint. Eight
      different procedural variations, marked by the addition of oxygen (four levels)
      and iron (two levels) were applied to Sangiovese wine, before and after
      malolactic fermentation. Data analysis using supervised and unsupervised
      multivariate methods highlighted some known candidate biomarkers, together with a
      number of metabolites which had never previously been considered as possible
      biomarkers for wine micro-oxygenation. Various pigments and tannins were
      identified among the known candidate biomarkers. Additional new information was
      obtained suggesting a correlation between oxygen doses and metal contents and
      changes in the concentration of primary metabolites such as arginine, proline,
      tryptophan and raffinose, and secondary metabolites such as succinic acid and
      xanthine. Based on these findings, new hypotheses regarding the formation and
      reactivity of wine pigment during micro-oxygenation have been proposed. This
      experiment highlights the feasibility of using unbiased, untargeted metabolomic
      fingerprinting to improve our understanding of wine chemistry.

PMID- 22662222
TI  - Inhibition of intestinal bile acid transporter Slc10a2 improves triglyceride
      metabolism and normalizes elevated plasma glucose levels in mice.
AB  - Interruption of the enterohepatic circulation of bile acids increases cholesterol
      catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We
      hypothesized that such treatment should lower the hepatic acetate pool which may
      alter triglyceride and glucose metabolism. We explored this using mice deficient
      of the ileal sodium-dependent BA transporter (Slc10a2) and ob/ob mice treated
      with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2
      deficient mice, and when challenged with a sucrose-rich diet, they displayed a
      reduced response in hepatic TG production as observed from the mRNA levels of
      several key enzymes in fatty acid synthesis. This effect was paralleled by a
      diminished induction of mature sterol regulatory element-binding protein 1c
      (Srebp1c). Unexpectedly, the SR-diet induced intestinal fibroblast growth factor
      (FGF) 15 mRNA and normalized bile acid synthesis in Slc10a2-/- mice.
      Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose,
      insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes.
      These responses are contrary to those reported following treatment of mice with a
      bile acid binding resin. Moreover, when key metabolic signal transduction
      pathways in the liver were investigated, those of Mek1/2-Erk1/2 and Akt were
      blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded
      that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in
      the diabetic ob/ob model it also reduces glucose and insulin levels. Hence,
      targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia
      and diabetes.

PMID- 22662223
TI  - Selection of aptamers specific for adipose tissue.
AB  - BACKGROUND: Obesity has reached epidemic proportions, affecting more than one
      tenth of the world's population. As such, adipose tissue is being increasingly
      recognized as an important therapeutic target for obesity and related metabolic
      disorders. While many potential targets of adipose tissue have been established
      and drugs developed, very few of those drugs specifically target adipose tissue
      without affecting other tissue. This results from a limited knowledge of both
      cell-surface markers and physicochemical traits specific to adipocytes that might
      otherwise be exploited by circulating drugs. METHODOLOGY/PRINCIPAL FINDINGS: Here
      we report the use of cell-SELEX technology to select two aptamers that can
      specifically recognize mature adipocytes: adipo-1 and adipo-8. Adipo-8 shows high
      affinity for differentiated, mature 3T3-L1 adipocytes with a K(d) value of 17.8+/
      5.1 nM. The binding was sustained upon incubation at 37 degrees C and insulin
      stimulation, but was lost upon trypsin treatment. The binding ability was also
      verified on frozen tissue slides with low background fluorescence and isolated
      adipocytes. CONCLUSIONS/SIGNIFICANCE: Aptamer adipo-8 selected from a random
      library appears to bind to mature differentiated adipocytes specifically. This
      aptamer holds great promise as a molecular recognition tool for adipocyte
      biomarker discovery or for targeted delivery of molecules to adipocytes.

PMID- 22662224
TI  - Sexual dimorphic regulation of body weight dynamics and adipose tissue lipolysis.
AB  - BACKGROUND: Successful reduction of body weight (BW) is often followed by
      recidivism to obesity. BW-changes including BW-loss and -regain is associated
      with marked alterations in energy expenditure (EE) and adipose tissue (AT)
      metabolism. Since these processes are sex-specifically controlled, we
      investigated sexual dimorphisms in metabolic processes during BW-dynamics (gain
      loss-regain). RESEARCH DESIGN: Obesity was induced in C57BL/6J male (m) and
      female (f) mice by 15 weeks high-fat diet (HFD) feeding. Subsequently BW was
      reduced (-20%) by caloric restriction (CR) followed by adaptive feeding, and a
      regain-phase. Measurement of EE, body composition, blood/organ sampling were
      performed after each feeding period. Lipolysis was analyzed ex-vivo in gonadal
      AT. RESULTS: Male mice exhibited accelerated BW-gain compared to females
      (relative BW-gain m:140.5+/-3.2%; f:103.7+/-6.5%; p<0.001). In consonance, lean
      mass-specific EE was significantly higher in females compared to males during BW
      gain. Under CR female mice reached their target-BW significantly faster than male
      mice (m:12.2 days; f:7.6 days; p<0.001) accompanied by a sustained sex-difference
      in EE. In addition, female mice predominantly downsized gonadal AT whereas the
      relation between gonadal and total body fat was not altered in males.
      Accordingly, only females exhibited an increased rate of forskolin-stimulated
      lipolysis in AT associated with significantly higher glycerol concentrations,
      lower RER-values, and increased AT expression of adipose triglyceride lipase
      (ATGL) and hormone sensitive lipase (HSL). Analysis of AT lipolysis in estrogen
      receptor alpha (ERalpha)-deficient mice revealed a reduced lipolytic rate in the
      absence of ERalpha exclusively in females. Finally, re-feeding caused BW-regain
      faster in males than in females. CONCLUSION: The present study shows sex-specific
      dynamics during BW-gain-loss-regain. Female mice responded to CR with an increase
      in lipolytic activity, and augmented lipid-oxidation leading to more efficient
      weight loss. These processes likely involve ERalpha-dependent signaling in AT and
      sexual dimorphic regulation of genes involved in lipid metabolism.

PMID- 22662225
TI  - Chronic exposure of corals to fine sediments: lethal and sub-lethal impacts.
AB  - Understanding the sedimentation and turbidity thresholds for corals is critical
      in assessing the potential impacts of dredging projects in tropical marine
      systems. In this study, we exposed two species of coral sampled from offshore
      locations to six levels of total suspended solids (TSS) for 16 weeks in the
      laboratory, including a 4 week recovery period. Dose-response relationships were
      developed to quantify the lethal and sub-lethal thresholds of sedimentation and
      turbidity for the corals. The sediment treatments affected the horizontal
      foliaceous species (Montipora aequituberculata) more than the upright branching
      species (Acropora millepora). The lowest sediment treatments that caused full
      colony mortality were 30 mg l(-1) TSS (25 mg cm(-2) day(-1)) for M.
      aequituberculata and 100 mg l(-1) TSS (83 mg cm(-2) day(-1)) for A. millepora
      after 12 weeks. Coral mortality generally took longer than 4 weeks and was
      closely related to sediment accumulation on the surface of the corals. While
      measurements of damage to photosystem II in the symbionts and reductions in lipid
      content and growth indicated sub-lethal responses in surviving corals, the most
      reliable predictor of coral mortality in this experiment was long-term sediment
      accumulation on coral tissue.

PMID- 22662226
TI  - Perivascular expression and potent vasoconstrictor effect of dynorphin A in
      cerebral arteries.
AB  - BACKGROUND: Numerous literary data indicate that dynorphin A (DYN-A) has a
      significant impact on cerebral circulation, especially under pathophysiological
      conditions, but its potential direct influence on the tone of cerebral vessels is
      obscure. The aim of the present study was threefold: 1) to clarify if DYN-A is
      present in cerebral vessels, 2) to determine if it exerts any direct effect on
      cerebrovascular tone, and if so, 3) to analyze the role of kappa-opiate receptors
      in mediating the effect. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemical
      analysis revealed the expression of DYN-A in perivascular nerves of rat pial
      arteries as well as in both rat and human intraparenchymal vessels of the
      cerebral cortex. In isolated rat basilar and middle cerebral arteries (BAs and
      MCAs) DYN-A (1-13) and DYN-A (1-17) but not DYN-A (1-8) or dynorphin B (DYN-B)
      induced strong vasoconstriction in micromolar concentrations. The maximal
      effects, compared to a reference contraction induced by 124 mM K(+), were 115+/
      6% and 104+/-10% in BAs and 113+/-3% and 125+/-9% in MCAs for 10 uM of DYN-A (1
      13) and DYN-A (1-17), respectively. The vasoconstrictor effects of DYN-A (1-13)
      could be inhibited but not abolished by both the kappa-opiate receptor antagonist
      nor-Binaltorphimine dihydrochloride (NORBI) and blockade of G(i/o)-protein
      mediated signaling by pertussis toxin. Finally, des-Tyr(1) DYN-A (2-13), which
      reportedly fails to activate kappa-opiate receptors, induced vasoconstriction of
      45+/-11% in BAs and 50+/-5% in MCAs at 10 uM, which effects were resistant to
      NORBI. CONCLUSION/SIGNIFICANCE: DYN-A is present in rat and human cerebral
      perivascular nerves and induces sustained contraction of rat cerebral arteries.
      This vasoconstrictor effect is only partly mediated by kappa-opiate receptors and
      heterotrimeric G(i/o)-proteins. To our knowledge our present findings are the
      first to indicate that DYN-A has a direct cerebral vasoconstrictor effect and
      that a dynorphin-induced vascular action may be, at least in part, independent of
      kappa-opiate receptors.

PMID- 22662227
TI  - Cardiac explant-derived cells are regulated by Notch-modulated mesenchymal
      transition.
AB  - BACKGROUND: Progenitor cell therapy is emerging as a novel treatment for heart
      failure. However the molecular mechanisms regulating the generation of cardiac
      progenitor cells is not fully understood. We hypothesized that cardiac progenitor
      cells are generated from cardiac explant via a process similar to epithelial to
      mesenchymal transition (EMT). METHODS/FINDINGS: Explant-derived cells were
      generated from partially digested atrial tissue. After 21 days in culture, c-Kit+
      cells were isolated from cell outgrowth. The majority of explant-originated c
      Kit+ cells expressed the epicardial marker Wt1. Cardiac cell outgrowth exhibits a
      temporal up-regulation of EMT-markers. Notch stimulation augmented, while Notch
      inhibition suppressed, mesenchymal transition in both c-Kit+ and c-Kit- cells. In
      c-Kit+ cells, Notch stimulation reduced, while Notch inhibition up-regulated
      pluripotency marker expressions such as Nanog and Sox2. Notch induction was
      associated with degradation of beta-catenin in c-Kit- cells. In contrast, Notch
      inhibition resulted in beta-catenin accumulation, acquisition of epitheloid
      morphology, and up-regulation of Wnt target genes in c-Kit- cells. CONCLUSION:
      Our study suggests that Notch-mediated reversible EMT process is a mechanism that
      regulates explant-derived c-Kit+ and c-Kit- cells.

PMID- 22662228
TI  - Involvement of SIK3 in glucose and lipid homeostasis in mice.
AB  - Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase,
      is induced in the murine liver after the consumption of a diet rich in fat,
      sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid
      metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3(-/-)
      mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia,
      hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and
      cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be
      due to reduced energy storage, which is represented by the low expression levels
      of mRNA for components of the fatty acid synthesis pathways in the liver. The
      biliary disorders in Sik3(-/-) mice are associated with the dysregulation of gene
      expression programs that respond to nutritional stresses and are probably
      regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and
      bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed
      at low levels in Sik3(-/-) mice. Lipid metabolism disorders in Sik3(-/-) mice are
      ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a
      novel energy regulator that modulates cholesterol and bile acid metabolism by
      coupling with retinoid metabolism, and may alter the size of energy storage in
      mice.

PMID- 22662229
TI  - Evidence for an African cluster of human head and body lice with variable colors
      and interbreeding of lice between continents.
AB  - BACKGROUND: Human head lice and body lice have been classified based on
      phenotypic characteristics, including geographical source, ecotype (preferred egg
      laying site hair or clothes), shape and color. More recently, genotypic studies
      have been based on mitochondrial genes, nuclear genes and intergenic spacers.
      Mitochondrial genetic analysis reclassified lice into three genotypes (A, B and
      C). However, no previous study has attempted to correlate both genotypic and
      phenotypic data. MATERIALS AND METHODS: Lice were collected in four African
      countries: Senegal, Burundi, Rwanda and Ethiopia and were photographed to compare
      their colors. The Multi-Spacer-Typing (MST) method was used to genotype lice
      belonging to the worldwide Clade A, allowing a comparison of phenotypic and
      genotypic data. RESULTS: No congruence between louse color and genotype has been
      identified. Phylogenetic analysis of the spacer PM2, performed including lice
      from other sources, showed the existence of an African cluster of human lice.
      However, the analysis of other spacers suggested that lice from different areas
      are interbreeding. CONCLUSIONS: We identified two geotypes of Clade A head and
      body lice including one that is specifically African, that can be either black or
      grey and can live on the head or in clothing. We also hypothesized that lice from
      different areas are interbreeding.

PMID- 22662230
TI  - Regulation of RKIP function by Helicobacter pylori in gastric cancer.
AB  - Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that
      infects more than half of the world's population and is a major cause of gastric
      adenocarcinoma. The mechanisms that link H. pylori infection to gastric
      carcinogenesis are not well understood. In the present study, we report that the
      Raf-kinase inhibitor protein (RKIP) has a role in the induction of apoptosis by
      H. pylori in gastric epithelial cells. Western blot and luciferase transcription
      reporter assays demonstrate that the pathogenicity island of H. pylori rapidly
      phosphorylates RKIP, which then localizes to the nucleus where it activates its
      own transcription and induces apoptosis. Forced overexpression of RKIP enhances
      apoptosis in H. pylori-infected cells, whereas RKIP RNA inhibition suppresses the
      induction of apoptosis by H. pylori infection. While inducing the phosphorylation
      of RKIP, H. pylori simultaneously targets non-phosphorylated RKIP for proteasome
      mediated degradation. The increase in RKIP transcription and phosphorylation is
      abrogated by mutating RKIP serine 153 to valine, demonstrating that regulation of
      RKIP activity by H. pylori is dependent upon RKIP's S153 residue. In addition, H.
      pylori infection increases the expression of Snail, a transcriptional repressor
      of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein,
      RKIP, to promote apoptosis in gastric cancer cells.

PMID- 22662231
TI  - Is the self always better than a friend? Self-face recognition in Christians and
      atheists.
AB  - Early behavioral studies found that human adults responded faster to their own
      faces than faces of familiar others or strangers, a finding referred to as self
      face advantage. Recent research suggests that the self-face advantage is mediated
      by implicit positive association with the self and is influenced by sociocultural
      experience. The current study investigated whether and how Christian belief and
      practice affect the processing of self-face in a Chinese population. Christian
      and Atheist participants were recruited for an implicit association test (IAT) in
      Experiment 1 and a face-owner identification task in Experiment 2. Experiment 1
      found that atheists responded faster to self-face when it shared the same
      response key with positive compared to negative trait adjectives. This IAT
      effect, however, was significantly reduced in Christians. Experiment 2 found that
      atheists responded faster to self-face compared to a friend's face, but this self
      face advantage was significantly reduced in Christians. Hierarchical regression
      analyses further showed that the IAT effect positively predicted self-face
      advantage in atheists but not in Christians. Our findings suggest that Christian
      belief and practice may weaken implicit positive association with the self and
      thus decrease the advantage of the self over a friend during face recognition in
      the believers.

PMID- 22662233
TI  - Bmp2, Bmp4 and Bmp7 are co-required in the mouse AER for normal digit patterning
      but not limb outgrowth.
AB  - Outgrowth and patterning of the vertebrate limb requires a functional apical
      ectodermal ridge (AER). The AER is a thickening of ectodermal tissue located at
      the distal end of the limb bud. Loss of this structure, either through genetic or
      physical manipulations results in truncation of the limb. A number of genes,
      including Bmps, are expressed in the AER. Previously, it was shown that removal
      of the BMP receptor Bmpr1a specifically from the AER resulted in complete loss of
      hindlimbs suggesting that Bmp signaling in the AER is required for limb
      outgrowth. In this report, we genetically removed the three known AER-expressed
      Bmp ligands, Bmp2, Bmp4 and Bmp7 from the AER of the limb bud using floxed
      conditional alleles and the Msx2-cre allele. Surprisingly, only defects in digit
      patterning and not limb outgrowth were observed. In triple mutants, the anterior
      and posterior AER was present but loss of the central region of the AER was
      observed. These data suggest that Bmp ligands expressed in the AER are not
      required for limb outgrowth but instead play an essential role in maintaining the
      AER and patterning vertebrate digits.

PMID- 22662232
TI  - Aetiologies of central nervous system infection in Viet Nam: a prospective
      provincial hospital-based descriptive surveillance study.
AB  - BACKGROUND: Infectious diseases of the central nervous system (CNS) remain common
      and life-threatening, especially in developing countries. Knowledge of the
      aetiological agents responsible for these infections is essential to guide
      empiric therapy and develop a rational public health policy. To date most data
      has come from patients admitted to tertiary referral hospitals in Asia and there
      is limited aetiological data at the provincial hospital level where most patients
      are seen. METHODS: We conducted a prospective Provincial Hospital-based
      descriptive surveillance study in adults and children at thirteen hospitals in
      central and southern Viet Nam between August 2007-April 2010. The pathogens of
      CNS infection were confirmed in CSF and blood samples by using classical
      microbiology, molecular diagnostics and serology. RESULTS: We recruited 1241
      patients with clinically suspected infection of the CNS. An aetiological agent
      was identified in 640/1241 (52%) of the patients. The most common pathogens were
      Streptococcus suis serotype 2 in patients older than 14 years of age (147/617,
      24%) and Japanese encephalitis virus in patients less than 14 years old (142/624,
      23%). Mycobacterium tuberculosis was confirmed in 34/617 (6%) adult patients and
      11/624 (2%) paediatric patients. The acute case fatality rate (CFR) during
      hospital admission was 73/617 (12%) in adults and to 42/624 (7%) in children.
      CONCLUSIONS: Zoonotic bacterial and viral pathogens are the most common causes of
      CNS infection in adults and children in Viet Nam.

PMID- 22662234
TI  - Rhodopsin expression level affects rod outer segment morphology and photoresponse
      kinetics.
AB  - BACKGROUND: The retinal rod outer segment is a sensory cilium that is specialized
      for the conversion of light into an electrical signal. Within the cilium, up to
      several thousand membranous disks contain as many as a billion copies of
      rhodopsin for efficient photon capture. Disks are continually turned over,
      requiring the daily synthesis of a prodigious amount of rhodopsin. To promote
      axial diffusion in the aqueous cytoplasm, the disks have one or more incisures.
      Across vertebrates, the range of disk diameters spans an order of magnitude, and
      the number and length of the incisures vary considerably, but the mechanisms
      controlling disk architecture are not well understood. The finding that
      transgenic mice overexpressing rhodopsin have enlarged disks lacking an incisure
      prompted us to test whether lowered rhodopsin levels constrain disk assembly.
      METHODOLOGY/PRINCIPAL FINDINGS: The structure and function of rods from
      hemizygous rhodopsin knockout (R+/-) mice with decreased rhodopsin expression
      were analyzed by transmission electron microscopy and single cell recording. R+/-
      rods were structurally altered in three ways: disk shape changed from circular to
      elliptical, disk surface area decreased, and the single incisure lengthened to
      divide the disk into two sections. Photocurrent responses to flashes recovered
      more rapidly than normal. A spatially resolved model of phototransduction
      indicated that changes in the packing densities of rhodopsin and other
      transduction proteins were responsible. The decrease in aqueous outer segment
      volume and the lengthened incisure had only minor effects on photon response
      amplitude and kinetics. CONCLUSIONS/SIGNIFICANCE: Rhodopsin availability limits
      disk assembly and outer segment girth in normal rods. The incisure may buffer the
      supply of structural proteins needed to form larger disks. Decreased rhodopsin
      level accelerated photoresponse kinetics by increasing the rates of molecular
      collisions on the membrane. Faster responses, together with fewer rhodopsins,
      combine to lower overall sensitivity of R+/- rods to light.

PMID- 22662235
TI  - Integrative gene regulatory network analysis reveals light-induced regional gene
      expression phase shift programs in the mouse suprachiasmatic nucleus.
AB  - We use the multigenic pattern of gene expression across suprachiasmatic nuclei
      (SCN) regions and time to understand the dynamics within the SCN in response to a
      circadian phase-resetting light pulse. Global gene expression studies of the SCN
      indicate that circadian functions like phase resetting are complex multigenic
      processes. While the molecular dynamics of phase resetting are not well
      understood, it is clear they involve a "functional gene expression program",
      e.g., the coordinated behavior of functionally related genes in space and time.
      In the present study we selected a set of 89 of these functionally related genes
      in order to further understand this multigenic program. By use of high-throughput
      qPCR we studied 52 small samples taken by anatomically precise laser capture from
      within the core and shell SCN regions, and taken at time points with and without
      phase resetting light exposure. The results show striking regional differences in
      light response to be present in the mouse SCN. By using network-based analyses,
      we are able to establish a highly specific multigenic correlation between genes
      expressed in response to light at night and genes normally activated during the
      day. The light pulse triggers a complex and highly coordinated network of gene
      regulation. The largest differences marking neuroanatomical location are in
      transmitter receptors, and the largest time-dependent differences occur in clock
      related genes. Nighttime phase resetting appears to recruit transcriptional
      regulatory processes normally active in the day. This program, or mechanism,
      causes the pattern of core region gene expression to transiently shift to become
      more like that of the shell region.

PMID- 22662236
TI  - Donor age of human platelet lysate affects proliferation and differentiation of
      mesenchymal stem cells.
AB  - The regenerative potential declines upon aging. This might be due to cell
      intrinsic changes in stem and progenitor cells or to influences by the
      microenvironment. Mesenchymal stem cells (MSC) raise high hopes in regenerative
      medicine. They are usually culture expanded in media with fetal calf serum (FCS)
      or other serum supplements such as human platelet lysate (HPL). In this study, we
      have analyzed the impact of HPL-donor age on culture expansion. 31 single donor
      derived HPLs (25 to 57 years old) were simultaneously compared for culture of
      MSC. Proliferation of MSC did not reveal a clear association with platelet counts
      of HPL donors or growth factors concentrations (PDGF-AB, TGF-beta1, bFGF, or IGF
      1), but it was significantly higher with HPLs from younger donors (<35 years) as
      compared to older donors (>45 years). Furthermore, HPLs from older donors
      increased activity of senescence-associated beta-galactosidase (SA-betagal). HPL
      donor age did not affect the fibroblastoid colony-forming unit (CFU-f) frequency,
      immunophenotype or induction of adipogenic differentiation, whereas osteogenic
      differentiation was significantly lower with HPLs from older donors.
      Concentrations of various growth factors (PDGF-AB, TGF-beta1, bFGF, IGF-1) or
      hormones (estradiol, parathormone, leptin, 1,25 vitamin D3) were not associated
      with HPL-donor age or MSC growth. Taken together, our data support the notion
      that aging is associated with systemic feedback mechanisms acting on stem and
      progenitor cells, and this is also relevant for serum supplements in cell
      culture: HPLs derived from younger donors facilitate enhanced expansion and more
      pronounced osteogenic differentiation.

PMID- 22662237
TI  - Down-regulation of GEP100 causes increase in E-cadherin levels and inhibits
      pancreatic cancer cell invasion.
AB  - AIMS: Invasion and metastasis are major reasons for pancreatic cancer death and
      identifying signaling molecules that are specifically used in tumor invasion is
      of great significance. The purpose of this study was to elucidate the role of
      GEP100 in pancreatic cancer cell invasion and metastasis and the corresponding
      molecular mechanism. METHODS: Stable cell lines with GEP100 knocked-down were
      established by transfecting GEP100 shRNA vector into PaTu8988 cells and selected
      by puromycin. qRT-PCR and Western blot were performed to detect gene expression.
      Matrigel-invasion assay was used to detect cancer cell invasion in vitro. Liver
      metastasis in vivo was determined by splenic injection of indicated cell lines
      followed by spleen resection. Immunofluorescence study was used to detect the
      intracellular localization of E-cadherin. RESULTS: We found that the expression
      level of GEP100 protein was closely related to the invasive ability of a panel of
      6 different human pancreatic cancer cell lines. Down-regulation of GEP100 in
      PaTu8988 cells significantly decreased invasive activity by Matrigel invasion
      assay, without affecting migration, invasion and viability. The inhibited
      invasive activity was rescued by over-expression of GEP100 cDNA. In vivo study
      showed that liver metastasis was significantly decreased in the PaTu8988 cells
      with GEP100 stably knocked-down. In addition, an epithelial-like morphological
      change, mimicking a mesenchymal to epithelial transition (MET) was induced by
      GEP100 down-regulation. The expression of E-cadherin protein was increased 2-3
      folds accompanied by its redistribution to the cell-cell contacts, while no
      obvious changes were observed for E-cadherin mRNA. Unexpectedly, the mRNA of Slug
      was increased by GEP100 knock-down. CONCLUSION: These findings provided important
      evidence that GEP100 plays a significant role in pancreatic cancer invasion
      through regulating the expression of E-cadherin and the process of MET,
      indicating the possibility of it becoming a potential therapeutic target against
      pancreatic cancer.

PMID- 22662238
TI  - Equity and geography: the case of child mortality in Papua New Guinea.
AB  - BACKGROUND: Recent assessments show continued decline in child mortality in Papua
      New Guinea (PNG), yet complete subnational analyses remain rare. This study aims
      to estimate under-five mortality in PNG at national and subnational levels to
      examine the importance of geographical inequities in health outcomes and track
      progress towards Millennium Development Goal (MDG) 4. METHODOLOGY: We performed
      retrospective data validation of the Demographic and Health Survey (DHS) 2006
      using 2000 Census data, then applied advanced indirect methods to estimate under
      five mortality rates between 1976 and 2000. FINDINGS: The DHS 2006 was found to
      be unreliable. Hence we used the 2000 Census to estimate under-five mortality
      rates at national and subnational levels. During the period under study, PNG
      experienced a slow reduction in national under-five mortality from approximately
      103 to 78 deaths per 1,000 live births. Subnational analyses revealed significant
      disparities between rural and urban populations as well as inter- and intra
      regional variations. Some of the provinces that performed the best (worst) in
      terms of under-five mortality included the districts that performed worst (best),
      with district-level under-five mortality rates correlating strongly with poverty
      levels and access to services. CONCLUSIONS: The evidence from PNG demonstrates
      substantial within-province heterogeneity, suggesting that under-five mortality
      needs to be addressed at subnational levels. This is especially relevant in
      countries, like PNG, where responsibility for health services is devolved to
      provinces and districts. This study presents the first comprehensive estimates of
      under-five mortality at the district level for PNG. The results demonstrate that
      for countries that rely on few data sources even greater importance must be given
      to the quality of future population surveys and to the exploration of alternative
      options of birth and death surveillance.

PMID- 22662239
TI  - Living on the edge: assessing the extinction risk of critically endangered
      Bonelli's eagle in Italy.
AB  - BACKGROUND: The population of Bonelli's eagle (Aquila fasciata) has declined
      drastically throughout its European range due to habitat degradation and
      unnatural elevated mortality. There are less than 1500 breeding pairs accounted
      for in Europe, and the species is currently catalogued as Critically Endangered
      in Italy, where the 22 territories of Sicily, represent nearly 95% of the entire
      Italian population. However, despite national and European conservation concerns,
      the species currently lacks a specific conservation plan, and no previous
      attempts to estimate the risk of extinction have been made. METHODOLOGY/PRINCIPAL
      FINDINGS: We incorporated the most updated demographic information available to
      assess the extinction risk of endangered Bonelli's eagle in Italy through a
      Population Viability Analysis. Using perturbation analyses (sensitivity and
      elasticity), and a combination of demographic data obtained from an assortment of
      independent methods, we evaluated which demographic parameters have more
      influence on the population's fate. We also simulated different scenarios to
      explore the effects of possible management actions. Our results showed that under
      the current conditions, Bonelli's eagle is expected to become extinct in Italy in
      less than 50 years. Stand-alone juvenile mortality was the most critical
      demographic parameter with the strongest influence on population persistence with
      respect to other demographic parameters. Measures aimed at either decreasing
      juvenile mortality, adult mortality or decreasing both juvenile and adult
      mortality resulted in equivalent net positive effects on population persistence
      (population growth rate lambda>1). In contrast, changes aimed at increasing
      breeding success had limited positive effects on demographic trends.
      CONCLUSIONS/SIGNIFICANCE: Our PVA provides essential information to direct the
      decision-making process and exposes gaps in our previous knowledge. To ensure the
      long-term persistence of the species in Italy, measures are urgently needed to
      decrease both adult mortality due to poaching and juvenile mortality due to nest
      plundering, the top ranking mortality causes.

PMID- 22662240
TI  - Nuclear Kaiso expression is associated with high grade and triple-negative
      invasive breast cancer.
AB  - Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in
      multiple cell types and functions as a transcriptional repressor and activator.
      Little is known about Kaiso expression and localization in breast cancer. Here,
      we have related pathological features and molecular subtypes to Kaiso expression
      in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly
      found in invasive ductal carcinoma (IDC) (p = 0.007), while cytoplasmic Kaiso
      expression was linked to invasive lobular carcinoma (ILC) (p = 0.006). Although
      cytoplasmic Kaiso did not correlate to clinicopathological features, we found a
      significant correlation between nuclear Kaiso, high histological grade (p =
      0.023), ERalpha negativity (p = 0.001), and the HER2-driven and basal/triple
      negative breast cancers (p = 0.018). Interestingly, nuclear Kaiso was also
      abundant in BRCA1-associated breast cancer (p<0.001) and invasive breast cancer
      overexpressing EGFR (p = 0.019). We observed a correlation between nuclear Kaiso
      and membrane-localized E-cadherin and p120-catenin (p120) (p<0.01). In contrast,
      cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear
      Kaiso (p = 0.005). We could confirm these findings in human ILC cells and cell
      lines derived from conditional mouse models of ILC. Moreover, we present
      functional data that substantiate a mechanism whereby E-cadherin controls p120
      mediated relief of Kaiso-dependent gene repression. In conclusion, our data
      indicate that nuclear Kaiso is common in clinically aggressive ductal breast
      cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent
      transcriptional repression characterize ILC.

PMID- 22662241
TI  - Growth inhibition and apoptosis induced by osthole, a natural coumarin, in
      hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed
      tumors worldwide and is known to be resistant to conventional chemotherapy. New
      therapeutic strategies are urgently needed for treating HCC. Osthole, a natural
      coumarin derivative, has been shown to have anti-tumor activity. However, the
      effects of osthole on HCC have not yet been reported. METHODS AND FINDINGS: HCC
      cell lines were treated with osthole at various concentrations for 24, 48 and 72
      hours. The proliferations of the HCC cells were measured by MTT assays. Cell
      cycle distribution and apoptosis were determined by flow cytometry. HCC tumor
      models were established in mice by subcutaneously injection of SMMC-7721 or Hepa1
      6 cells and the effect of osthole on tumor growths in vivo and the drug toxicity
      were studied. NF-kappaB activity after osthole treatment was determined by
      electrophoretic mobility shift assays and the expression of caspase-3 was
      measured by western blotting. The expression levels of other apoptosis-related
      genes were also determined by real-time PCR (PCR array) assays. Osthole displayed
      a dose- and time-dependent inhibition of the HCC cell proliferations in vitro. It
      also induced apoptosis and caused cell accumulation in G2 phase. Osthole could
      significantly suppress HCC tumor growth in vivo with no toxicity at the dose we
      used. NF-kappaB activity was significantly suppressed by osthole at the dose- and
      time-dependent manner. The cleaved caspase-3 was also increased by osthole
      treatment. The expression levels of some apoptosis-related genes that belong to
      TNF ligand family, TNF receptor family, Bcl-2 family, caspase family, TRAF
      family, death domain family, CIDE domain and death effector domain family and
      CARD family were all increased with osthole treatment. CONCLUSION: Osthole could
      significantly inhibit HCC growth in vitro and in vivo through cell cycle arrest
      and inducing apoptosis by suppressing NF-kappaB activity and promoting the
      expressions of apoptosis-related genes.

PMID- 22662242
TI  - Replication and fine mapping for association of the C2orf43, FOXP4, GPRC6A and
      RFX6 genes with prostate cancer in the Chinese population.
AB  - BACKGROUND: Prostate cancer represents the leading cause of male death across the
      world. A recent genome-wide association study (GWAS) identified five novel
      susceptibility loci for prostate cancer in the Japanese population. This study is
      to replicate and fine map the potential association of these five loci with
      prostate cancer in the Chinese Han population. METHODS: In Phase I of the study,
      we tested the five single nucleotide polymorphisms (SNPs) which showed the
      strongest association evidence in the original GWAS in Japanese. The study sample
      consists of 1,169 Chinese Hans, comprising 483 patients and 686 healthy controls.
      Then in phase II, flanking SNPs of the successfully replicated SNPs in Phase I
      were genotyped and tested for association with prostate cancer to fine map those
      significant association signals. RESULTS: We successfully replicated the
      association of rs13385191 (located in the C2orf43 gene, P = 8.60*10(-5)),
      rs12653946 (P = 1.33*10(-6)), rs1983891 (FOXP4, P = 6.22*10(-5)), and rs339331
      (GPRC6A/RFX6, P = 1.42*10(-5)) with prostate cancer. The most significant odds
      ratio (OR) was recorded as 1.41 (95% confidence interval 1.18-1.68) for
      rs12653946. Rs9600079 did not show significant association (P = 8.07*10(-2)) with
      prostate cancer in this study. The Phase II study refined these association
      signals, and identified several SNPs showing more significant association with
      prostate cancer than the very SNPs tested in Phase I. CONCLUSIONS: Our results
      provide further support for association of the C2orf43, FOXP4, GPRC6A and RFX6
      genes with prostate cancer in Eastern Asian populations. This study also
      characterized the novel loci reported in the original GWAS with more details.
      Further work is still required to determine the functional variations and finally
      clarify the underlying biological mechanisms.

PMID- 22662243
TI  - Meta-analysis of the association between transforming growth factor-beta
      polymorphisms and complications of coronary heart disease.
AB  - OBJECTIVE: To investigate the association between common transforming growth
      factor beta (TGF-beta) single nucleotide polymorphisms (SNP) and significant
      complications of coronary heart disease (CHD). METHOD: We performed a meta
      analysis of published case-control studies assessing the association of TGF-beta
      SNPs with a range of CHD complications. A random effects model was used to
      calculate odds ratios and confidence intervals. Analyses were conducted for
      additive, dominant and recessive modes of inheritance. RESULTS: Six studies
      involving 5535 cases and 2970 controls examining the association of common SNPs
      in TGF-beta1 with CHD were identified. Applying a dominant model of inheritance,
      three TGF-beta1 SNPs were significantly associated with CHD complications: The T
      alleles of rs1800469 (OR = 1.125, 95% CI 1.016-1.247, p = 0.031) and rs1800470
      (OR = 1.146, 95% CI 1.026-1.279, p = 0.021); and the C allele of rs1800471 (OR =
      1.207, 95% CI 1.037-1.406, p = 0.021). CONCLUSION: This meta-analysis suggests
      that common genetic polymorphisms in TGF-beta1 are associated with complications
      of CHD.

PMID- 22662244
TI  - The KRAS-variant is associated with risk of developing double primary breast and
      ovarian cancer.
AB  - PURPOSE: A germline microRNA binding site-disrupting variant, the KRAS-variant
      (rs61764370), is associated with an increased risk of developing several cancers.
      Because this variant is most strongly associated with ovarian cancer risk in
      patients from hereditary breast and ovarian families (HBOC), and with the risk of
      premenopausal triple negative breast cancer, we evaluated the association of the
      KRAS-variant with women with personal histories of both breast and ovarian
      cancer, referred to as double primary patients. EXPERIMENTAL DESIGN: Germline DNA
      from double primary patients was tested for the KRAS-variant (n = 232).
      Confirmation of pathologic diagnoses, age of diagnoses, interval between ovarian
      cancer diagnosis and sample collection, additional cancer diagnoses, and family
      history were obtained when available. All patients were tested for deleterious
      BRCA mutations. RESULTS: The KRAS-variant was significantly enriched in
      uninformative (BRCA negative) double primary patients, being found in 39% of
      patients accrued within two years of their ovarian cancer diagnosis. Furthermore,
      the KRAS-variant was found in 35% of uninformative double primary patients
      diagnosed with ovarian cancer post-menopausally, and was significantly associated
      with uninformative double primary patients with a positive family history. The
      KRAS-variant was also significantly enriched in uninformative patients who
      developed more then two primary cancers, being found in 48% of women with two
      breast primaries plus ovarian cancer or with triple primary cancers. CONCLUSIONS:
      These findings further validate the importance of the KRAS-variant in breast and
      ovarian cancer risk, and support the association of this variant as a genetic
      marker for HBOC families previously considered uninformative.

PMID- 22662245
TI  - Electronic sensors for assessing interactions between healthcare workers and
      patients under airborne precautions.
AB  - BACKGROUND: Direct observation has been widely used to assess interactions
      between healthcare workers (HCWs) and patients but is time-consuming and feasible
      only over short periods. We used a Radio Frequency Identification Device (RFID)
      system to automatically measure HCW-patient interactions. METHODS: We equipped 50
      patient rooms with fixed sensors and 111 HCW volunteers with mobile sensors in
      two clinical wards of two hospitals. For 3 months, we recorded all interactions
      between HCWs and 54 patients under airborne precautions for suspected (n = 40) or
      confirmed (n = 14) tuberculosis. Number and duration of HCW entries into patient
      rooms were collected daily. Concomitantly, we directly observed room entries and
      interviewed HCWs to evaluate their self-perception of the number and duration of
      contacts with tuberculosis patients. RESULTS: After signal reconstruction, 5490
      interactions were recorded between 82 HCWs and 54 tuberculosis patients during
      404 days of airborne isolation. Median (interquartile range) interaction duration
      was 2.1 (0.8-4.4) min overall, 2.3 (0.8-5.0) in the mornings, 1.8 (0.8-3.7) in
      the afternoons, and 2.0 (0.7-4.3) at night (P<10(-4)). Number of
      interactions/day/HCW was 3.0 (1.0-6.0) and total daily duration was 7.6 (2.4
      22.5) min. Durations estimated from 28 direct observations and 26 interviews were
      not significantly different from those recorded by the network. CONCLUSIONS: The
      RFID was well accepted by HCWs. This original technique holds promise for
      accurately and continuously measuring interactions between HCWs and patients, as
      a less resource-consuming substitute for direct observation. The results could be
      used to model the transmission of significant pathogens. HCW perceptions of
      interactions with patients accurately reflected reality.

PMID- 22662246
TI  - Diurnal rhythms in neurexins transcripts and inhibitory/excitatory synapse
      scaffold proteins in the biological clock.
AB  - The neurexin genes (NRXN1/2/3) encode two families (alpha and beta) of highly
      polymorphic presynaptic proteins that are involved in excitatory/inhibitory
      synaptic balance. Recent studies indicate that neuronal activation and memory
      formation affect NRXN1/2/3alpha expression and alternative splicing at splice
      sites 3 and 4 (SS#3/SS#4). Neurons in the biological clock residing in the
      suprachiasmatic nuclei of the hypothalamus (SCN) act as self-sustained
      oscillators, generating rhythms in gene expression and electrical activity, to
      entrain circadian bodily rhythms to the 24 hours day/night cycles. Cell
      autonomous oscillations in NRXN1/2/3alpha expression and SS#3/SS#4 exons splicing
      and their links to rhythms in excitatory/inhibitory synaptic balance in the
      circadian clock were explored. NRXN1/2/3alpha expression and SS#3/SS#4 splicing,
      levels of neurexin-2alpha and the synaptic scaffolding proteins PSD-95 and
      gephyrin (representing excitatory and inhibitory synapses, respectively) were
      studied in mRNA and protein extracts obtained from SCN of C3H/J mice at different
      times of the 24 hours day/night cycle. Further studies explored the circadian
      oscillations in these components and causality relationships in immortalized rat
      SCN2.2 cells. Diurnal rhythms in mNRXN1alpha and mNRXN2alpha transcription,
      SS#3/SS#4 exon-inclusion and PSD-95 gephyrin and neurexin-2alpha levels were
      found in the SCN in vivo. No such rhythms were found with mNRXN3alpha. SCN2.2
      cells also exhibited autonomous circadian rhythms in rNRXN1/2 expression
      SS#3/SS#4 exon inclusion and PSD-95, gephyrin and neurexin-2alpha levels.
      rNRXN3alpha and rNRXN1/2beta were not expressed. Causal relationships were
      demonstrated, by use of specific siRNAs, between rNRXN2alpha SS#3 exon included
      transcripts and gephyrin levels in the SCN2.2 cells. These results show for the
      first time dynamic, cell autonomous, diurnal rhythms in expression and splicing
      of NRXN1/2 and subsequent effects on the expression of neurexin-2alpha and
      postsynaptic scaffolding proteins in SCN across the 24-h cycle. NRXNs gene
      transcripts may have a role in coupling the circadian clock to diurnal rhythms in
      excitatory/inhibitory synaptic balance.

PMID- 22662247
TI  - Individual and contextual factors associated with low childhood immunisation
      coverage in sub-Saharan Africa: a multilevel analysis.
AB  - BACKGROUND: In 2010, more than six million children in sub-Saharan Africa did not
      receive the full series of three doses of the diphtheria-tetanus-pertussis
      vaccine by one year of age. An evidence-based approach to addressing this burden
      of un-immunised children requires accurate knowledge of the underlying factors.
      We therefore developed and tested a model of childhood immunisation that includes
      individual, community and country-level characteristics. METHOD AND FINDINGS: We
      conducted multilevel logistic regression analysis of Demographic and Health
      Survey data for 27,094 children aged 12-23 months, nested within 8,546
      communities from 24 countries in sub-Saharan Africa. According to the intra
      country and intra-community correlation coefficient implied by the estimated
      intercept component variance, 21% and 32% of the variance in unimmunised children
      were attributable to country- and community-level factors respectively. Children
      born to mothers (OR 1.35, 95%CI 1.18 to 1.53) and fathers (OR 1.13, 95%CI 1.12 to
      1.40) with no formal education were more likely to be unimmunised than those born
      to parents with secondary or higher education. Children from the poorest
      households were 36% more likely to be unimmunised than counterparts from the
      richest households. Maternal access to media significantly reduced the odds of
      children being unimmunised (OR 0.94, 95%CI 0.94 to 0.99). Mothers with health
      seeking behaviours were less likely to have unimmunised children (OR 0.56, 95%CI
      0.54 to 0.58). However, children from urban areas (OR 1.12, 95% CI 1.01 to 1.23),
      communities with high illiteracy rates (OR 1.13, 95% CI 1.05 to 1.23), and
      countries with high fertility rates (OR 4.43, 95% CI 1.04 to 18.92) were more
      likely to be unimmunised. CONCLUSION: We found that individual and contextual
      factors were associated with childhood immunisation, suggesting that public
      health programmes designed to improve coverage of childhood immunisation should
      address people, and the communities and societies in which they live.

PMID- 22662248
TI  - Statistical methods used to test for agreement of medical instruments measuring
      continuous variables in method comparison studies: a systematic review.
AB  - BACKGROUND: Accurate values are a must in medicine. An important parameter in
      determining the quality of a medical instrument is agreement with a gold
      standard. Various statistical methods have been used to test for agreement. Some
      of these methods have been shown to be inappropriate. This can result in
      misleading conclusions about the validity of an instrument. The Bland-Altman
      method is the most popular method judging by the many citations of the article
      proposing this method. However, the number of citations does not necessarily mean
      that this method has been applied in agreement research. No previous study has
      been conducted to look into this. This is the first systematic review to identify
      statistical methods used to test for agreement of medical instruments. The
      proportion of various statistical methods found in this review will also reflect
      the proportion of medical instruments that have been validated using those
      particular methods in current clinical practice. METHODOLOGY/FINDINGS: Five
      electronic databases were searched between 2007 and 2009 to look for agreement
      studies. A total of 3,260 titles were initially identified. Only 412 titles were
      potentially related, and finally 210 fitted the inclusion criteria. The Bland
      Altman method is the most popular method with 178 (85%) studies having used this
      method, followed by the correlation coefficient (27%) and means comparison (18%).
      Some of the inappropriate methods highlighted by Altman and Bland since the 1980s
      are still in use. CONCLUSIONS: This study finds that the Bland-Altman method is
      the most popular method used in agreement research. There are still inappropriate
      applications of statistical methods in some studies. It is important for a
      clinician or medical researcher to be aware of this issue because misleading
      conclusions from inappropriate analyses will jeopardize the quality of the
      evidence, which in turn will influence quality of care given to patients in the
      future.

PMID- 22662249
TI  - Induction of neuronal death by microglial AGE-albumin: implications for
      Alzheimer's disease.
AB  - Advanced glycation end products (AGEs) have long been considered as potent
      molecules promoting neuronal cell death and contributing to neurodegenerative
      disorders such as Alzheimer's disease (AD). In this study, we demonstrate that
      AGE-albumin, the most abundant AGE product in human AD brains, is synthesized in
      activated microglial cells and secreted into the extracellular space. The rate of
      AGE-albumin synthesis in human microglial cells is markedly increased by amyloid
      beta exposure and oxidative stress. Exogenous AGE-albumin upregulates the
      receptor protein for AGE (RAGE) and augments calcium influx, leading to apoptosis
      of human primary neurons. In animal experiments, soluble RAGE (sRAGE),
      pyridoxamine or ALT-711 prevented Abeta-induced neuronal death in rat brains.
      Collectively, these results provide evidence for a new mechanism by which
      microglial cells promote death of neuronal cells through synthesis and secretion
      of AGE-albumin, thereby likely contributing to neurodegenerative diseases such as
      AD.

PMID- 22662250
TI  - H19 antisense RNA can up-regulate Igf2 transcription by activation of a novel
      promoter in mouse myoblasts.
AB  - It was recently shown that a long non-coding RNA (lncRNA), that we named the 91H
      RNA (i.e. antisense H19 transcript), is overexpressed in human breast tumours and
      contributes in trans to the expression of the Insulin-like Growth Factor 2 (IGF2)
      gene on the paternal chromosome. Our preliminary experiments suggested that an
      H19 antisense transcript having a similar function may also be conserved in the
      mouse. In the present work, we further characterise the mouse 91H RNA and, using
      a genetic complementation approach in H19 KO myoblast cells, we show that ectopic
      expression of the mouse 91H RNA can up-regulate Igf2 expression in trans despite
      almost complete unmethylation of the Imprinting-Control Region (ICR). We then
      demonstrate that this activation occurs at the transcriptional level by
      activation of a previously unknown Igf2 promoter which displays, in mouse
      tissues, a preferential mesodermic expression (Pm promoter). Finally, our
      experiments indicate that a large excess of the H19 transcript can counteract 91H
      mediated Igf2 activation. Our work contributes, in conjunction with other recent
      findings, to open new horizons to our understanding of Igf2 gene regulation and
      functions of the 91H/H19 RNAs in normal and pathological conditions.

PMID- 22662251
TI  - Internal ribosomal entry site-mediated translation is important for rhythmic
      PERIOD1 expression.
AB  - The mouse PERIOD1 (mPER1) plays an important role in the maintenance of circadian
      rhythm. Translation of mPer1 is directed by both a cap-dependent process and cap
      independent translation mediated by an internal ribosomal entry site (IRES) in
      the 5' untranslated region (UTR). Here, we compared mPer1 IRES activity with
      other cellular IRESs. We also found critical region in mPer1 5'UTR for
      heterogeneous nuclear ribonucleoprotein Q (HNRNPQ) binding. Deletion of HNRNPQ
      binding region markedly decreased IRES activity and disrupted rhythmicity. A
      mathematical model also suggests that rhythmic IRES-dependent translation is a
      key process in mPER1 oscillation. The IRES-mediated translation of mPer1 will
      help define the post-transcriptional regulation of the core clock genes.

PMID- 22662252
TI  - Dufulin activates HrBP1 to produce antiviral responses in tobacco.
AB  - BACKGROUND: Dufulin is a new antiviral agent that is highly effective against
      plant viruses and acts by activating systemic acquired resistance (SAR) in
      plants. In recent years, it has been used widely to prevent and control tobacco
      and rice viral diseases in China. However, its targets and mechanism of action
      are still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Here, differential
      in-gel electrophoresis (DIGE) and classical two-dimensional electrophoresis (2
      DE) techniques were combined with mass spectrometry (MS) to identify the target
      of Dufulin. More than 40 proteins were found to be differentially expressed
      (>=1.5 fold or <=1.5 fold) upon Dufulin treatment in Nicotiana tabacum K(326).
      Based on annotations in the Gene Ontology (GO) and the Kyoto Encyclopedia of
      Genes and Genomes (KEGG) databases, these proteins were found to be related to
      disease resistance. Directed acyclic graph (DAG) analysis of the various pathways
      demonstrated harpin binding protein-1 (HrBP1) as the target of action of Dufulin.
      Additionally, western blotting, semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR), and real time PCR analyses were also
      conducted to identify the specific mechanism of action of Dufulin. Our results
      show that activation of HrBP1 triggers the salicylic acid (SA) signaling pathway
      and thereby produces antiviral responses in the plant host. A protective assay
      based on lesion counting further confirmed the antiviral activity of Dufulin.
      CONCLUSION: This study identified HrBP1 as a target protein of Dufulin and that
      Dufulin can activate the SA signaling pathway to induce host plants to generate
      antiviral responses.

PMID- 22662253
TI  - The satellite cell in male and female, developing and adult mouse muscle:
      distinct stem cells for growth and regeneration.
AB  - Satellite cells are myogenic cells found between the basal lamina and the
      sarcolemma of the muscle fibre. Satellite cells are the source of new myofibres;
      as such, satellite cell transplantation holds promise as a treatment for muscular
      dystrophies. We have investigated age and sex differences between mouse satellite
      cells in vitro and assessed the importance of these factors as mediators of donor
      cell engraftment in an in vivo model of satellite cell transplantation. We found
      that satellite cell numbers are increased in growing compared to adult and in
      male compared to female adult mice. We saw no difference in the expression of the
      myogenic regulatory factors between male and female mice, but distinct profiles
      were observed according to developmental stage. We show that, in contrast to
      adult mice, the majority of satellite cells from two week old mice are
      proliferating to facilitate myofibre growth; however a small proportion of these
      cells are quiescent and not contributing to this growth programme. Despite
      observed changes in satellite cell populations, there is no difference in
      engraftment efficiency either between satellite cells derived from adult or pre
      weaned donor mice, male or female donor cells, or between male and female host
      muscle environments. We suggest there exist two distinct satellite cell
      populations: one for muscle growth and maintenance and one for muscle
      regeneration.

PMID- 22662254
TI  - Regulation of adipocyte 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
      by CCAAT/enhancer-binding protein (C/EBP) beta isoforms, LIP and LAP.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyses intracellular
      regeneration of active glucocorticoids, notably in liver and adipose tissue.
      11beta-HSD1 is increased selectively in adipose tissue in human obesity, a change
      implicated in the pathogenesis of metabolic syndrome. With high fat (HF)-feeding,
      adipose tissue 11beta-HSD1 is down-regulated in mice, plausibly to counteract
      metabolic disease. Transcription of 11beta-HSD1 is directly regulated by members
      of the CCAAT/enhancer binding protein (C/EBP) family. Here we show that while
      total C/EBPbeta in adipose tissue is unaltered by HF diet, the ratio of the
      C/EBPbeta isoforms liver-enriched inhibitor protein (LIP) and liver-enriched
      activator protein (LAP) (C/EBPbeta-LIP:LAP) is increased in subcutaneous adipose.
      This may cause changes in 11beta-HSD1 expression since genetically modified
      C/EBPbeta((+/L)) mice, with increased C/EBPbeta-LIP:LAP ratio, have decreased
      subcutaneous adipose 11beta-HSD1 mRNA levels, whereas C/EBPbeta(DeltauORF) mice,
      with decreased C/EBPbeta-LIP:LAP ratio, show increased subcutaneous adipose
      11beta-HSD1. C/EBPbeta-LIP:LAP ratio is regulated by endoplasmic reticulum (ER)
      stress and mTOR signalling, both of which are altered in obesity. In 3T3-L1
      adipocytes, 11beta-HSD1 mRNA levels were down-regulated following induction of ER
      stress by tunicamycin but were up-regulated following inhibition of mTOR by
      rapamycin. These data point to a central role for C/EBPbeta and its processing to
      LIP and LAP in transcriptional regulation of 11beta-HSD1 in adipose tissue. Down
      regulation of 11beta-HSD1 by increased C/EBPbeta-LIP:LAP in adipocytes may be
      part of a nutrient-sensing mechanism counteracting nutritional stress generated
      by HF diet.

PMID- 22662255
TI  - Indomethacin reduces glomerular and tubular damage markers but not renal
      inflammation in chronic kidney disease patients: a post-hoc analysis.
AB  - Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs) may be
      used to lower therapy-resistant proteinuria. The potentially beneficial anti
      proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be
      offset by an increased risk of (renal) side effects. We investigated the effect
      of indomethacin on urinary markers of glomerular and tubular damage and renal
      inflammation. We performed a post-hoc analysis of a prospective open-label
      crossover study in chronic kidney disease patients (n = 12) with mild renal
      function impairment and stable residual proteinuria of 4.7+/-4.1 g/d. After a
      wash-out period of six wks without any RAAS blocking agents or other therapy to
      lower proteinuria (untreated proteinuria (UP)), patients subsequently received
      indomethacin 75 mg BID for 4 wks (NSAID). Healthy subjects (n = 10) screened for
      kidney donation served as controls. Urine and plasma levels of total IgG, IgG4,
      KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA.
      Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal
      tubular damage markers was reduced in comparison with the period without anti
      proteinuric treatment (total IgG: UP 131[38-513] vs NSAID 38[17-218] mg/24 h,
      p<0.01; IgG4: 50[16-68] vs 10[1-38] mg/24 h, p<0.001; beta-2-microglobulin:
      200[55-404] vs 50[28-110] ug/24 h, p = 0.03; KIM-1: 9[5]-[14] vs 5[2]-[9] ug/24
      h, p = 0.01). Fractional excretions of these damage markers were also reduced by
      NSAID. The distal tubular marker H-FABP showed a trend to reduction following
      NSAID treatment. Surprisingly, NSAID treatment did not reduce urinary excretion
      of the inflammation markers MCP-1 and NGAL, but did reduce plasma MCP-1 levels,
      resulting in an increased fractional MCP-1 excretion. In conclusion, the anti
      proteinuric effect of indomethacin is associated with reduced urinary excretion
      of glomerular and tubular damage markers, but not with reduced excretion of renal
      inflammation markers. Future studies should address whether the short term
      glomerulo- and tubulo-protective effects as observed outweigh the possible side
      effects of NSAID treatment on the long term.

PMID- 22662256
TI  - Validation of a semi-quantitative Food Frequency Questionnaire for Argentinean
      adults.
AB  - BACKGROUND: The Food Frequency Questionnaire (FFQ) is the most commonly used
      method for ranking individuals based on long term food intake in large
      epidemiological studies. The validation of an FFQ for specific populations is
      essential as food consumption is culture dependent. The aim of this study was to
      develop a Semi-quantitative Food Frequency Questionnaire (SFFQ) and evaluate its
      validity and reproducibility in estimating nutrient intake in urban and rural
      areas of Argentina. METHODS/PRINCIPAL FINDINGS: Overall, 256 participants in the
      Argentinean arm of the ongoing Prospective Urban and Rural Epidemiological study
      (PURE) were enrolled for development and validation of the SFFQ. One hundred
      individuals participated in the SFFQ development. The other 156 individuals
      completed the SFFQs on two occasions, four 24-hour Dietary Recalls (24DRs) in
      urban, and three 24DRs in rural areas during a one-year period. Correlation
      coefficients (r) and de-attenuated correlation coefficients between 24DRs and
      SFFQ were calculated for macro and micro-nutrients. The level of agreement
      between the two methods was evaluated using classification into same and extreme
      quartiles and the Bland-Altman method. The reproducibility of the SFFQ was
      assessed by Pearson correlation coefficients and Intra-class Correlation
      Coefficients (ICC). The SFFQ consists of 96 food items. In both urban and rural
      settings de-attenuated correlations exceeded 0.4 for most of the nutrients. The
      classification into the same and adjacent quartiles was more than 70% for urban
      and 60% for rural settings. The Pearson correlation between two SFFQs varied from
      0.30-0.56 and 0.32-0.60 in urban and rural settings, respectively. CONCLUSION:
      Our results showed that this SFFQ had moderate relative validity and
      reproducibility for macro and micronutrients in relation to the comparison method
      and can be used to rank individuals based on habitual nutrient intake.

PMID- 22662257
TI  - Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis,
      cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway.
AB  - Curcumin, the active component of turmeric, has been shown to protect against
      carcinogenesis and prevent tumor development. However, little is known about its
      anti-tumor mechanism in small cell lung cancer (SCLC). In this study, we found
      that curcumin can inhibit SCLC cell proliferation, cell cycle, migration,
      invasion and angiogenesis through suppression of the STAT3. SCLC cells were
      treated with curcumin (15 umol/L) and the results showed that curcumin was
      effective in inhibiting STAT3 phosphorylation to downregulate of an array of
      STAT3 downstream targets ,which contributed to suppression of cell proliferation,
      loss of colony formation, depression of cell migration and invasion. Curcumin
      also suppressed the expression of proliferative proteins (Survivin, Bcl-X(L) and
      Cyclin B1), and invasive proteins (VEGF, MMP-2, MMP-7 and ICAM-1). Knockdown of
      STAT3 expression by siRNA was able to induce anti-invasive effects in vitro. In
      contrast, activation of STAT3 upstream of interleukin 6 (IL-6) leads to the
      increased cell proliferation ,cell survival, angiogenesis, invasion, migration
      and tumor growth. Our findings illustrate the biologic significance of IL
      6/JAK/STAT3 signaling in SCLC progression and provide novel evidence that the
      pathway may be a new potential target for therapy of SCLC. It was concluded that
      curcumin is a potent agent in the inhibition of STAT3 with favorable
      pharmacological activity,and curcumin may have translational potential as an
      effective cancer therapeutic or preventive agent for SCLC.

PMID- 22662258
TI  - Deep-time phylogenetic clustering of extinctions in an evolutionarily dynamic
      clade (Early Jurassic ammonites).
AB  - Conservation biologists and palaeontologists are increasingly investigating the
      phylogenetic distribution of extinctions and its evolutionary consequences.
      However, the dearth of palaeontological studies on that subject and the lack of
      methodological consensus hamper our understanding of that major evolutionary
      phenomenon. Here we address this issue by (i) reviewing the approaches used to
      quantify the phylogenetic selectivity of extinctions and extinction risks; (ii)
      investigating with a high-resolution dataset whether extinctions and survivals
      were phylogenetically clustered among early Pliensbachian (Early Jurassic)
      ammonites; (iii) exploring the phylogenetic and temporal maintenance of this
      signal. We found that ammonite extinctions were significantly clumped
      phylogenetically, a pattern that prevailed throughout the 6.6 Myr-long early
      Pliensbachian interval. Such a phylogenetic conservatism did not alter--or may
      even have promoted--the evolutionary success of this major cephalopod clade.
      However, the comparison of phylogenetic autocorrelation among studies remains
      problematic because the notion of phylogenetic conservatism is scale-dependent
      and the intensity of the signal is sensitive to temporal resolution. We recommend
      a combined use of Moran's I, Pearson's phi and Fritz and Purvis' D statistics
      because they highlight different facets of the phylogenetic pattern of
      extinctions and/or survivals.

PMID- 22662259
TI  - Pulmonary tuberculosis and delay in anti-tuberculous treatment are important risk
      factors for chronic obstructive pulmonary disease.
AB  - OBJECTIVE: Tuberculosis (TB) remains the leading cause of death among infectious
      diseases worldwide. It has been suggested as an important risk factor of chronic
      obstructive pulmonary disease (COPD), which is also a major cause of morbidity
      and mortality. This study investigated the impact of pulmonary TB and anti-TB
      treatment on the risk of developing COPD. DESIGN, SETTING, AND PARTICIPANTS: This
      cohort study used the National Health Insurance Database of Taiwan, particularly
      the Longitudinal Health Insurance Database 2005 to obtain 3,176 pulmonary TB
      cases and 15,880 control subjects matched in age, sex, and timing of entering the
      database. MAIN OUTCOME MEASURES: Hazard ratios of potential risk factors of COPD,
      especially pulmonary TB and anti-TB treatment. RESULTS: The mean age of pulmonary
      TB cases was 51.9+/-19.2. The interval between the initial study date and
      commencement of anti-TB treatment (delay in anti-TB treatment) was 75.8+/-65.4
      days. Independent risk factors for developing COPD were age, male, low income,
      and history of pulmonary TB (hazard ratio 2.054 [1.768-2.387]), while diabetes
      mellitus was protective. The impact of TB persisted for six years after TB
      diagnosis and was significant in women and subjects aged >70 years. Among TB
      patients, delay in anti-TB treatment had a dose-response relationship with the
      risk of developing COPD. CONCLUSIONS: Some cases of COPD may be preventable by
      controlling the TB epidemic, early TB diagnosis, and prompt initiation of
      appropriate anti-TB treatment. Follow-up care and early intervention for COPD may
      be necessary for treated TB patients.

PMID- 22662260
TI  - Food anticipatory activity behavior of mice across a wide range of circadian and
      non-circadian intervals.
AB  - When rodents are fed in a limited amount during the daytime, they rapidly
      redistribute some of their nocturnal activity to the time preceding the delivery
      of food. In rats, anticipation of a daily meal has been interpreted as a
      circadian rhythm controlled by a food-entrained oscillator (FEO) with circadian
      limits to entrainment. Lesion experiments place this FEO outside of the light
      entrainable circadian pacemaker in the suprachiasmatic nucleus. Mice also
      anticipate a fixed daily meal, but circadian limits to entrainment and
      anticipation of more than 2 daily meals, have not been assessed. We used a video
      based behavior recognition system to quantify food anticipatory activity in mice
      receiving 2, 3, or 6 daily meals at intervals of 12, 8, or 4-hours (h).
      Individual mice were able to anticipate as many as 4 of 6 daily meals, and
      anticipation persisted during meal omission tests. On the 6 meal schedule, pre
      prandial activity and body temperature were poorly correlated, suggesting
      independent regulation. Mice showed a limited ability to anticipate an 18 h
      feeding schedule. Finally, mice showed concurrent circadian and sub-hourly
      anticipation when provided with 6 small meals, at 30 minute intervals, at a fixed
      time of day. These results indicate that mice can anticipate feeding
      opportunities at a fixed time of day across a wide range of intervals not
      previously associated with anticipatory behavior in studies of rats. The methods
      described here can be exploited to determine the extent to which timing of
      different intervals in mice relies on common or distinct neural and molecular
      mechanisms.

PMID- 22662262
TI  - Health-related quality of life in long-term survivors of relapsed childhood acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Relapses occur in about 20% of children with acute lymphoblastic
      leukemia (ALL). Approximately one-third of these children can be cured. Their
      risk for late effects is high because of intensified treatment, but their health
      related quality of life (HRQOL) was largely unmeasured. Our aim was to compare
      HRQOL of ALL survivors with the general population, and of relapsed with non
      relapsed ALL survivors. METHODOLOGY/PRINCIPAL FINDINGS: As part of the Swiss
      Childhood Cancer Survivor Study (SCCSS) we sent a questionnaire to all ALL
      survivors in Switzerland who had been diagnosed between 1976-2003 at age <16
      years, survived >=5 years, and were currently aged >=16 years. HRQOL was assessed
      with the Short Form-36 (SF-36), which measures four aspects of physical health
      and four aspects of mental health. A score of 50 corresponded to the mean of a
      healthy reference population. We analyzed data from 457 ALL survivors (response:
      79%). Sixty-one survivors had suffered a relapse. Compared to the general
      population, ALL survivors reported similar or higher HRQOL scores on all scales.
      Survivors with a relapse scored lower in general health perceptions (51.6)
      compared to those without (55.8;p=0.005), but after adjusting for self-reported
      late effects, this difference disappeared. CONCLUSION/SIGNIFICANCE: Compared to
      population norms, ALL survivors reported good HRQOL, even after a relapse.
      However, relapsed ALL survivors reported poorer general health than non-relapsed.
      Therefore, we encourage specialists to screen for poor general health in
      survivors after a relapse and, when appropriate, specifically seek and treat
      underlying late effects. This will help to improve patients' HRQOL.

PMID- 22662261
TI  - Geminin is required for zygotic gene expression at the Xenopus mid-blastula
      transition.
AB  - In many organisms early development is under control of the maternal genome and
      zygotic gene expression is delayed until the mid-blastula transition (MBT). As
      zygotic transcription initiates, cell cycle checkpoints become activated and the
      tempo of cell division slows. The mechanisms that activate zygotic transcription
      at the MBT are incompletely understood, but they are of interest because they may
      resemble mechanisms that cause stem cells to stop dividing and terminally
      differentiate. The unstable regulatory protein Geminin is thought to coordinate
      cell division with cell differentiation. Geminin is a bi-functional protein. It
      prevents a second round of DNA replication during S and G2 phase by binding and
      inhibiting the essential replication factor Cdt1. Geminin also binds and inhibits
      a number of transcription factors and chromatin remodeling proteins and is
      thought to keep dividing cells in an undifferentiated state. We previously found
      that the cells of Geminin-deficient Xenopus embryos arrest in G2 phase just after
      the MBT then disintegrate at the onset of gastrulation. Here we report that they
      also fail to express most zygotic genes. The gene expression defect is cell
      autonomous and is reproduced by over-expressing Cdt1 or by incubating the embryos
      in hydroxyurea. Geminin deficient and hydroxyurea-treated blastomeres accumulate
      DNA damage in the form of double stranded breaks. Bypassing the Chk1 pathway
      overcomes the cell cycle arrest caused by Geminin depletion but does not restore
      zygotic gene expression. In fact, bypassing the Chk1 pathway by itself induces
      double stranded breaks and abolishes zygotic transcription. We did not find
      evidence that Geminin has a replication-independent effect on transcription. We
      conclude that Geminin is required to maintain genome integrity during the rapid
      cleavage divisions, and that DNA damage disrupts zygotic gene transcription at
      the MBT, probably through activation of DNA damage checkpoint pathways.

PMID- 22662263
TI  - COPI is required for enterovirus 71 replication.
AB  - Enterovirus 71 (EV71), a member of the Picornaviridae family, is found in Asian
      countries where it causes a wide range of human diseases. No effective therapy is
      available for the treatment of these infections. Picornaviruses undergo RNA
      replication in association with membranes of infected cells. COPI and COPII have
      been shown to be involved in the formation of picornavirus-induced vesicles.
      Replication of several picornaviruses, including poliovirus and Echovirus 11
      (EV11), is dependent on COPI or COPII. Here, we report that COPI, but not COPII,
      is required for EV71 replication. Replication of EV71 was inhibited by brefeldin
      A and golgicide A, inhibitors of COPI activity. Furthermore, we found EV71 2C
      protein interacted with COPI subunits by co-immunoprecipitation and GST pull-down
      assay, indicating that COPI coatomer might be directed to the viral replication
      complex through viral 2C protein. Additionally, because the pathway is conserved
      among different species of enteroviruses, it may represent a novel target for
      antiviral therapies.

PMID- 22662264
TI  - A policy-into-practice intervention to increase the uptake of evidence-based
      management of low back pain in primary care: a prospective cohort study.
AB  - BACKGROUND: Persistent non-specific low back pain (nsLBP) is poorly understood by
      the general community, by educators, researchers and health professionals, making
      effective care problematic. This study evaluated the effectiveness of a policy
      into-practice intervention developed for primary care physicians (PCPs). METHODS:
      To encourage PCPs to adopt practical evidence-based approaches and facilitate
      time-efficient, integrated management of patients with nsLBP, we developed an
      interdisciplinary evidence-based, practical pain education program (gPEP) based
      on a contemporary biopsychosocial framework. One hundred and twenty six PCPs from
      primary care settings in Western Australia were recruited. PCPs participated in a
      6.5-hour gPEP. Self-report measures recorded at baseline and at 2 months post
      intervention included PCPs' attitudes, beliefs (modified Health Care Providers
      Pain and Impairment Relationship Scale (HC-PAIRS), evidence-based clinical
      practices (knowledge and skills regarding nsLBP management: 5-point Likert scale
      with 1  =  nil and 5  =  excellent) and practice behaviours (recommendations
      based on a patient vignette; 5-point Likert scale). RESULTS: Ninety one PCPs
      participated (attendance rate of 72%; post-intervention response rate 88%). PCP
      responders adopted more positive, guideline-consistent beliefs, evidenced by
      clinically significant HC-PAIRS score differences (mean change  =  -5.6+/-8.2,
      p<0.0001; 95% confidence interval: -7.6 to -3.6) and significant positive shifts
      on all measures of clinical knowledge and skills (p<0.0001 for all questions).
      Self management strategies were recommended more frequently post-intervention.
      The majority of responders who were guideline-inconsistent for work and bed rest
      recommendations (82% and 62% respectively) at pre-intervention, gave guideline
      consistent responses at post-intervention. CONCLUSION: An interprofessional pain
      education program set within a framework that aligns health policy and practice,
      encourages PCPs to adopt more self-reported evidence-based attitudes, beliefs and
      clinical behaviours in their management of patients with nsLBP. However, further
      research is required to determine cost effectiveness of this approach when
      compared with other modes of educational delivery and to examine PCP behaviours
      in actual clinical practice.

PMID- 22662265
TI  - Exome sequencing and genetic testing for MODY.
AB  - CONTEXT: Genetic testing for monogenic diabetes is important for patient care.
      Given the extensive genetic and clinical heterogeneity of diabetes, exome
      sequencing might provide additional diagnostic potential when standard Sanger
      sequencing-based diagnostics is inconclusive. OBJECTIVE: The aim of the study was
      to examine the performance of exome sequencing for a molecular diagnosis of MODY
      in patients who have undergone conventional diagnostic sequencing of candidate
      genes with negative results. RESEARCH DESIGN AND METHODS: We performed exome
      enrichment followed by high-throughput sequencing in nine patients with suspected
      MODY. They were Sanger sequencing-negative for mutations in the HNF1A, HNF4A,
      GCK, HNF1B and INS genes. We excluded common, non-coding and synonymous gene
      variants, and performed in-depth analysis on filtered sequence variants in a pre
      defined set of 111 genes implicated in glucose metabolism. RESULTS: On average,
      we obtained 45 X median coverage of the entire targeted exome and found 199 rare
      coding variants per individual. We identified 0-4 rare non-synonymous and
      nonsense variants per individual in our a priori list of 111 candidate genes.
      Three of the variants were considered pathogenic (in ABCC8, HNF4A and PPARG,
      respectively), thus exome sequencing led to a genetic diagnosis in at least three
      of the nine patients. Approximately 91% of known heterozygous SNPs in the target
      exomes were detected, but we also found low coverage in some key diabetes genes
      using our current exome sequencing approach. Novel variants in the genes ARAP1,
      GLIS3, MADD, NOTCH2 and WFS1 need further investigation to reveal their possible
      role in diabetes. CONCLUSION: Our results demonstrate that exome sequencing can
      improve molecular diagnostics of MODY when used as a complement to Sanger
      sequencing. However, improvements will be needed, especially concerning coverage,
      before the full potential of exome sequencing can be realized.

PMID- 22662266
TI  - Respiratory syncytial virus matrix protein induces lung epithelial cell cycle
      arrest through a p53 dependent pathway.
AB  - Respiratory syncytial virus (RSV) is the major cause of viral respiratory
      infections in children. Our previous study showed that the RSV infection induced
      lung epithelial cell cycle arrest, which enhanced virus replication. To address
      the mechanism of RSV-induced cell cycle arrest, we examined the contribution of
      RSV-matrix (RSV-M) protein. In this report, we show that in both the A549 cell
      line and primary human bronchial epithelial (PHBE) cells, transfection with RSV-M
      protein caused the cells to proliferate at a slower rate than in control cells.
      The cell cycle analysis showed that RSV-M protein induced G1 phase arrest in A549
      cells, and G1 and G2/M phase arrest in PHBE cells. Interestingly, RSV-M
      expression induced p53 and p21 accumulation and decreased phosphorylation of
      retinoblastoma protein (Rb). Further, induction of cell cycle arrest by RSV-M was
      not observed in a p53-deficient epithelial cell line (H1299). However, cell cycle
      arrest was restored after transfection of p53 cDNA into H1299 cells. Taken
      together, these results indicate that RSV-M protein regulates lung epithelial
      cell cycle through a p53-dependent pathway, which enhances RSV replication.

PMID- 22662268
TI  - Frailty and its impact on health-related quality of life: a cross-sectional study
      on elder community-dwelling preventive health service users.
AB  - BACKGROUND: The purpose of this study was to identify the incidence of frailty
      and to investigate the relationship between frailty status and health-related
      quality of life (HRQoL) in the community-dwelling elderly population who utilize
      preventive health services. METHODS: People aged 65 years and older who visited a
      medical center in Taipei City from March to August in 2011 for an annual routine
      check-up provided by the National Health Insurance were eligible. A total of 374
      eligible elderly adults without cognitive impairment had a mean age of 74.6+/-6.3
      years. Frailty status was determined according to the Fried frailty criteria.
      HRQoL was measured with Short Form-36 (SF-36). Multiple regression analyses
      examined the relationship between frailty status and the two summary scales of SF
      36. Models were adjusted for the participants' sociodemographic and health
      status. RESULTS: After adjusting for sociodemographic and health-related
      covariables, frailty was found to be more significantly associated (p<0.001) with
      lower scores on both physical and mental health-related quality of life summary
      scales compared with robustness. For the frailty phenotypes, slowness represented
      the major contributing factor in the physical component scale of SF-36, and
      exhaustion was the primary contributing factor in the mental component scale.
      CONCLUSION: The status of frailty is closely associated with HRQoL in elderly
      Taiwanese preventive health service users. The impacts of frailty phenotypes on
      physical and mental aspects of HRQoL differ.

PMID- 22662267
TI  - Cdc42-dependent activation of NADPH oxidase is involved in ethanol-induced
      neuronal oxidative stress.
AB  - It has been suggested that excessive reactive oxygen species (ROS) and oxidative
      stress play an important role in ethanol-induced damage to both the developing
      and mature central nervous system (CNS). The mechanisms underlying ethanol
      induced neuronal ROS, however, remain unclear. In this study, we investigated the
      role of NADPH oxidase (NOX) in ethanol-induced ROS generation. We demonstrated
      that ethanol activated NOX and inhibition of NOX reduced ethanol-promoted ROS
      generation. Ethanol significantly increased the expression of p47(phox) and
      p67(phox), the essential subunits for NOX activation in cultured neuronal cells
      and the cerebral cortex of infant mice. Ethanol caused serine phosphorylation and
      membrane translocation of p47(phox) and p67(phox), which were prerequisites for
      NOX assembly and activation. Knocking down p47(phox) with the small interfering
      RNA was sufficient to attenuate ethanol-induced ROS production and ameliorate
      ethanol-mediated oxidative damage, which is indicated by a decrease in protein
      oxidation and lipid peroxidation. Ethanol activated cell division cycle 42
      (Cdc42) and overexpression of a dominant negative (DN) Cdc42 abrogate ethanol
      induced NOX activation and ROS generation. These results suggest that Cdc42
      dependent NOX activation mediates ethanol-induced oxidative damages to neurons.

PMID- 22662269
TI  - Mate-finding as an overlooked critical determinant of dispersal variation in
      sexually-reproducing animals.
AB  - Dispersal is a critically important process in ecology, but robust predictive
      models of animal dispersal remain elusive. We identify a potentially ubiquitous
      component of variation in animal dispersal that has been largely overlooked until
      now: the influence of mate encounters on settlement probability. We use an
      individual-based model to simulate dispersal in sexually-reproducing organisms
      that follow a simple set of movement rules based on conspecific encounters,
      within an environment lacking spatial habitat heterogeneity. We show that
      dispersal distances vary dramatically with fluctuations in population density in
      such a model, even in the absence of variation in dispersive traits between
      individuals. In a simple random-walk model with promiscuous mating, dispersal
      distributions become increasingly 'fat-tailed' at low population densities due to
      the increasing scarcity of mates. Similar variation arises in models
      incorporating territoriality. In a model with polygynous mating, we show that
      patterns of sex-biased dispersal can even be reversed across a gradient of
      population density, despite underlying dispersal mechanisms remaining unchanged.
      We show that some widespread dispersal patterns found in nature (e.g. fat tailed
      distributions) can arise as a result of demographic variability in the absence of
      heterogeneity in dispersive traits across the population. This implies that
      models in which individual dispersal distances are considered to be fixed traits
      might be unrealistic, as dispersal distances vary widely under a single dispersal
      mechanism when settlement is influenced by mate encounters. Mechanistic models
      offer a promising means of advancing our understanding of dispersal in sexually
      reproducing organisms.

PMID- 22662270
TI  - Interactions between surround suppression and interocular suppression in human
      vision.
AB  - Several types of suppression phenomena have been observed in the visual system.
      For example, the ability to detect a target stimulus is often impaired when the
      target is embedded in a high-contrast surround. This contextual modulation, known
      as surround suppression, was formerly thought to occur only in the periphery.
      Another type of suppression phenomena is interocular suppression, in which the
      sensitivity to a monocular target is reduced by a superimposed mask in the
      opposite eye. Here, we explored how the two types of suppression operating across
      different spatial regions interact with one another when they simultaneously
      exert suppressive influences on a common target presented at the fovea. In our
      experiments, a circular target grating presented to the fovea of one eye was
      suppressed interocularly by a noise pattern of the same size in the other eye.
      The foveal stimuli were either shown alone or surrounded by a monocular annular
      grating. The orientation and eye-of-origin of the surround grating were varied.
      We found that the detection of the foveal target subjected to interocular
      suppression was severely impaired by the addition of the surround grating,
      indicating strong surround suppression in the fovea. In contrast, when the
      interocular suppression was released by superimposing a binocular fusion ring
      onto both the target and the dichoptic mask, the surround suppression effect was
      found to be dramatically decreased. In addition, the surround suppression was
      found to depend on the contrast of the dichoptic noise with the greatest surround
      suppression effect being obtained only when the noise contrast was at an
      intermediate level. These findings indicate that surround suppression and
      interocular suppression are not independent of each other, but there are strong
      interactions between them. Moreover, our results suggest that strong surround
      suppression may also occur at the fovea and not just the periphery.

PMID- 22662271
TI  - Pathogenicity of aseptic Bursaphelenchus xylophilus.
AB  - Pine wilt is a disease of pine (Pinus spp.) caused by the pine wood nematode
      (PWN), Bursaphelenchus xylophilus. However, the pathogenic mechanism of pine wilt
      disease (PWD) remains unclear. Although the PWN was thought to be the only
      pathogenic agent associated with this disease, a potential role for bacterial
      symbionts in the disease process was recently proposed. Studies have indicated
      that aseptic PWNs do not cause PWD in aseptic pine trees, while PWNs associated
      with bacteria cause wilting symptoms. To investigate the pathogenicity of the PWN
      and its associated bacteria, 3-month-old microcuttings derived from certain
      clones of Pinus densiflora Siebold & Zucc. produced in vitro were inoculated
      under aseptic conditions with aseptic PWNs, non-aseptic PWNs and bacteria
      isolated from the nematodes. Six-month-old aseptic P. densiflora microcuttings
      and 7-month-old P. massoniana seedlings were also inoculated under aseptic
      conditions with aseptic PWNs and non-aseptic PWNs. The results showed that the
      aseptic microcuttings and seedlings inoculated with aseptic PWNs or non-aseptic
      PWNs wilted, while those inoculated with bacterial isolates did not wilt.
      Nematodes were recovered from wilted microcuttings and seedlings inoculated with
      aseptic PWNs and non-aseptic PWNs, and the asepsis of nematodes recovered from
      aseptic PWN-inoculated microcuttings and seedlings was reconfirmed by culturing
      them in NB liquid medium at 30 degrees C for more than 7 days. Taken together,
      the results indicate that the asepsis of PWN did not cause the loss of
      pathogenicity.

PMID- 22662272
TI  - Three-dimensional, tomographic super-resolution fluorescence imaging of serially
      sectioned thick samples.
AB  - Three-dimensional fluorescence imaging of thick tissue samples with near
      molecular resolution remains a fundamental challenge in the life sciences. To
      tackle this, we developed tomoSTORM, an approach combining single-molecule
      localization-based super-resolution microscopy with array tomography of
      structurally intact brain tissue. Consecutive sections organized in a ribbon were
      serially imaged with a lateral resolution of 28 nm and an axial resolution of 40
      nm in tissue volumes of up to 50 um*50 um*2.5 um. Using targeted expression of
      membrane bound (m)GFP and immunohistochemistry at the calyx of Held, a model
      synapse for central glutamatergic neurotransmission, we delineated the course of
      the membrane and fine-structure of mitochondria. This method allows multiplexed
      super-resolution imaging in large tissue volumes with a resolution three orders
      of magnitude better than confocal microscopy.

PMID- 22662273
TI  - Effect of spermidine on misfolding and interactions of alpha-synuclein.
AB  - Alpha-synuclein (alpha-Syn) is a 140 aa presynaptic protein which belongs to a
      group of natively unfolded proteins that are unstructured in aqueous solutions.
      The aggregation rate of alpha-Syn is accelerated in the presence of physiological
      levels of cellular polyamines. Here we applied single molecule AFM force
      spectroscopy to characterize the effect of spermidine on the very first stages of
      alpha-Syn aggregation--misfolding and assembly into dimers. Two alpha-Syn
      variants, the wild-type (WT) protein and A30P, were studied. The two protein
      molecules were covalently immobilized at the C-terminus, one at the AFM tip and
      the other on the substrate, and intermolecular interactions between the two
      molecules were measured by multiple approach-retraction cycles. At conditions
      close to physiological ones at which alpha-Syn misfolding is a rare event, the
      addition of spermidine leads to a dramatic increase in the propensity of the WT
      and mutant proteins to misfold. Importantly, misfolding is characterized by a set
      of conformations, and A30P changes the misfolding pattern as well as the strength
      of the intermolecular interactions. Together with the fact that spermidine
      facilitates late stages of alpha-Syn aggregation, our data demonstrate that
      spermidine promotes the very early stages of protein aggregation including alpha
      Syn misfolding and dimerization. This finding suggests that increased levels of
      spermidine and potentially other polyamines can initiate the disease-related
      process of alpha-Syn.

PMID- 22662274
TI  - Comparative analysis of PvPAP gene family and their functions in response to
      phosphorus deficiency in common bean.
AB  - BACKGROUND: Purple acid phosphatases (PAPs) play a vital role in adaptive
      strategies of plants to phosphorus (P) deficiency. However, their functions in
      relation to P efficiency are fragmentary in common bean. PRINCIPAL FINDINGS: Five
      PvPAPs were isolated and sequenced in common bean. Phylogenetic analysis showed
      that PvPAPs could be classified into two groups, including a small group with low
      molecular mass, and a large group with high molecular mass. Among them, PvPAP3,
      PvPAP4 and PvPAP5 belong to the small group, while the other two belong to the
      large group. Transient expression of 35S:PvPAPs-GFP on onion epidermal cells
      verified the variations of subcellular localization among PvPAPs, suggesting
      functional diversities of PvPAPs in common bean. Quantitative PCR results showed
      that most PvPAPs were up-regulated by phosphate (Pi) starvation. Among them, the
      expression of the small group PvPAPs responded more to Pi starvation, especially
      in the roots of G19833, the P-efficient genotype. However, only overexpressing
      PvPAP1 and PvPAP3 could result in significantly increased utilization of
      extracellular dNTPs in the transgenic bean hairy roots. Furthermore,
      overexpressing PvPAP3 in Arabidopsis enhanced both plant growth and total P
      content when dNTPs were supplied as the sole external P source. CONCLUSIONS: The
      results suggest that PvPAPs in bean varied in protein structure, response to P
      deficiency and subcellular localization. Among them, both PvPAP1 and PvPAP3 might
      function as utilization of extracellular dNTPs.

PMID- 22662275
TI  - The epitope and neutralization mechanism of AVFluIgG01, a broad-reactive human
      monoclonal antibody against H5N1 influenza virus.
AB  - The continued spread of highly pathogenic avian influenza (HPAI) H5N1 virus
      underscores the importance of effective antiviral approaches. AVFluIgG01 is a
      potent and broad-reactive H5N1-neutralizing human monoclonal antibody (mAb)
      showing great potential for use either for therapeutic purposes or as a basis of
      vaccine development, but its antigenic epitope and neutralization mechanism have
      not been finely characterized. In this study, we first demonstrated that
      AVFluIgG01 targets a novel conformation-dependent epitope in the globular head
      region of H5N1 hemagglutinin (HA). By selecting mimotopes from a random peptide
      library in combination with computational algorithms and site-directed
      mutagenesis, the epitope was mapped to three conserved discontinuous sites (I
      III) that are located closely at the three-dimensional structure of HA. Further,
      we found that this HA1-specific human mAb can efficiently block both virus
      receptor binding and post-attachment steps, while its Fab fragment exerts the
      post-attachment inhibition only. Consistently, AVFluIgG01 could inhibit HA
      mediated cell-cell membrane fusion at a dose-dependent manner and block the
      acquisition of pH-induced protease sensitivity. These results suggest a
      neutralization mechanism of AVFluIgG01 by simultaneously blocking viral
      attachment to the receptors on host cells and interfering with HA conformational
      rearrangements associated with membrane fusion. The presented data provide
      critical information for developing novel antiviral therapeutics and vaccines
      against HPAI H5N1 virus.

PMID- 22662277
TI  - Responsive electrical stimulation suppresses epileptic seizures in rats.
AB  - BACKGROUND: A responsive electrical stimulation pattern based on our recently
      developed novel seizure prediction method was designed to suppress the penicillin
      induced epileptic seizures. METHODOLOGY: Seizures were induced by Penicillin
      injection at rat cortex. A responsive electrical stimulation system was triggered
      prior to seizures predicted with phase synchronisation. Rats with induced
      seizures were stimulated by the electrical pulses at a responsive or 1 Hz
      periodic pattern of an open system. The effectiveness of stimulation on seizures
      suppression was assessed by measuring the average number and duration of seizures
      per hour. RESULTS: The prediction algorithm reliably identified seizures in real
      time and triggered the responsive stimulation. This type of electrical
      stimulation dramatically suppressed seizure activity and the performance was
      better than the open stimulation system with fewer and shorter seizures.
      CONCLUSIONS: A responsive electrical stimulation system triggered by the phase
      synchronisation prediction is able to significantly suppress seizures.
      SIGNIFICANCE: Responsive electrical stimulation could achieve superior treatment
      performance and reduce power consumption and side effects.

PMID- 22662276
TI  - Inhibition of neuroblastoma tumor growth by targeted delivery of microRNA-34a
      using anti-disialoganglioside GD2 coated nanoparticles.
AB  - BACKGROUND: Neuroblastoma is one of the most challenging malignancies of
      childhood, being associated with the highest death rate in paediatric oncology,
      underlining the need for novel therapeutic approaches. Typically, patients with
      high risk disease undergo an initial remission in response to treatment, followed
      by disease recurrence that has become refractory to further treatment. Here, we
      demonstrate the first silica nanoparticle-based targeted delivery of a tumor
      suppressive, pro-apoptotic microRNA, miR-34a, to neuroblastoma tumors in a murine
      orthotopic xenograft model. These tumors express high levels of the cell surface
      antigen disialoganglioside GD2 (GD(2)), providing a target for tumor-specific
      delivery. PRINCIPAL FINDINGS: Nanoparticles encapsulating miR-34a and conjugated
      to a GD(2) antibody facilitated tumor-specific delivery following systemic
      administration into tumor bearing mice, resulted in significantly decreased tumor
      growth, increased apoptosis and a reduction in vascularisation. We further
      demonstrate a novel, multi-step molecular mechanism by which miR-34a leads to
      increased levels of the tissue inhibitor metallopeptidase 2 precursor (TIMP2)
      protein, accounting for the highly reduced vascularisation noted in miR-34a
      treated tumors. SIGNIFICANCE: These novel findings highlight the potential of
      anti-GD(2)-nanoparticle-mediated targeted delivery of miR-34a for both the
      treatment of GD(2)-expressing tumors, and as a basic discovery tool for
      elucidating biological effects of novel miRNAs on tumor growth.

PMID- 22662278
TI  - 2D and 3D-organized cardiac cells shows differences in cellular morphology,
      adhesion junctions, presence of myofibrils and protein expression.
AB  - Cardiac cells are organized in vivo in a complex tridimensional structural
      organization that is crucial for heart function. While in vitro studies can
      reveal details about cardiac cell biology, usually cells are grown on simplified
      two-dimensional (2D) environments. To address these differences, we established a
      cardiac cell culture composed of both 2D and three-dimensional (3D)-organized
      cells. Our results shows significant differences between the two culture contexts
      in relation to the overall morphology of the cells, contraction ability,
      proliferation rate, presence of intercellular adhesion structures, organization
      of myofibrils, mitochondria morphology, endoplasmic reticulum contents,
      cytoskeletal filaments and extracellular matrix distribution, and expression of
      markers of cardiac differentiation. Cardiac cells grown in 2D-context displayed a
      flattened and well spread shape, were mostly isolated and their cytoplasm was
      filled with a large network of microfilaments and microtubules. In contrast, 3D
      cells were smaller in size, were always in close contact with each other with
      several cellular junctions, and displayed a less conspicuous cytoskeletal
      network. 3D-cells had more mitochondria and myofibrils and these cells contract
      spontaneously more often than 2D-cells. On the other hand, endoplasmic reticulum
      membranes were present in higher amounts in 2D-cells when compared to 3D-cells.
      The expression of desmin, cadherin and alpha-actinin was higher in 3D-aggregates
      compared to 2D-spread cells. These findings indicate that the tridimensional
      environment in which the cardiac cells are grown influence several aspects of
      cardiac differentiation, including cell adhesion, cell shape, myofibril assembly,
      mitochondria contents and protein expression. We suggest that the use of this
      cardiac culture model, with 2D and 3D-context cells, could be useful for studies
      on the effects of different drugs, or growth factors, giving valuable information
      on the biological response of cells grown in different spatial organizations.

PMID- 22662279
TI  - Functional interaction between human papillomavirus type 16 E6 and E7
      oncoproteins and cigarette smoke components in lung epithelial cells.
AB  - The smoking habit is the most important, but not a sufficient cause for lung
      cancer development. Several studies have reported the human papillomavirus type
      16 (HPV16) presence and E6 and E7 transcripts expression in lung carcinoma cases
      from different geographical regions. The possible interaction between HPV
      infection and smoke carcinogens, however, remains unclear. In this study we
      address a potential cooperation between tobacco smoke and HPV16 E6 and E7
      oncoproteins for alterations in proliferative and tumorigenic properties of lung
      epithelial cells. A549 (alveolar, tumoral) and BEAS-2B (bronchial, non-tumoral)
      cell lines were stably transfected with recombinant pLXSN vectors expressing
      HPV16 E6 and E7 oncoproteins and exposed to cigarette smoke condensate (CSC) at
      different concentrations. HPV16 E6 and E7 expression was associated with loss of
      p53 stability, telomerase (hTERT) and p16(INK4A) overexpression in BEAS-2B cells
      as demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR) and
      western blotting (WB). In A549 cells we observed downregulation of p53 but not a
      significant increase of hTERT transcripts. In addition, the HPV16 E6/E7
      transfected cell lines showed an increased proliferation rate and anchorage
      independent growth in a HPV16 E6 and E7 expression-dependent manner. Moreover,
      both HPV16 E6/E7 and mock transfected cells showed an increased proliferation
      rate and anchorage-independent growth in the presence of 0.1 and 10 ug/mL CSC.
      However, this increase was significantly greater in HPV16 E6/E7 transfected cells
      (p<0.001). Data were confirmed by FCSE proliferation assay. The results obtained
      in this study are suggestive of a functional interaction between tobacco smoke
      and HPV16 E6/E7 oncoproteins for malignant transformation and tumorigenesis of
      lung epithelial cells. More studies are warranted in order to dissect the
      molecular mechanisms involved in this cooperation.

PMID- 22662280
TI  - Metagenomic and metabolic profiling of nonlithifying and lithifying stromatolitic
      mats of Highborne Cay, The Bahamas.
AB  - BACKGROUND: Stromatolites are laminated carbonate build-ups formed by the
      metabolic activity of microbial mats and represent one of the oldest known
      ecosystems on Earth. In this study, we examined a living stromatolite located
      within the Exuma Sound, The Bahamas and profiled the metagenome and metabolic
      potential underlying these complex microbial communities. METHODOLOGY/PRINCIPAL
      FINDINGS: The metagenomes of the two dominant stromatolitic mat types, a
      nonlithifying (Type 1) and lithifying (Type 3) microbial mat, were partially
      sequenced and compared. This deep-sequencing approach was complemented by
      profiling the substrate utilization patterns of the mats using metabolic
      microarrays. Taxonomic assessment of the protein-encoding genes confirmed
      previous SSU rRNA analyses that bacteria dominate the metagenome of both mat
      types. Eukaryotes comprised less than 13% of the metagenomes and were rich in
      sequences associated with nematodes and heterotrophic protists. Comparative
      genomic analyses of the functional genes revealed extensive similarities in most
      of the subsystems between the nonlithifying and lithifying mat types. The one
      exception was an increase in the relative abundance of certain genes associated
      with carbohydrate metabolism in the lithifying Type 3 mats. Specifically, genes
      associated with the degradation of carbohydrates commonly found in exopolymeric
      substances, such as hexoses, deoxy- and acidic sugars were found. The genetic
      differences in carbohydrate metabolisms between the two mat types were confirmed
      using metabolic microarrays. Lithifying mats had a significant increase in
      diversity and utilization of carbon, nitrogen, phosphorus and sulfur substrates.
      CONCLUSION/SIGNIFICANCE: The two stromatolitic mat types retained similar
      microbial communities, functional diversity and many genetic components within
      their metagenomes. However, there were major differences detected in the activity
      and genetic pathways of organic carbon utilization. These differences provide a
      strong link between the metagenome and the physiology of the mats, as well as new
      insights into the biological processes associated with carbonate precipitation in
      modern marine stromatolites.

PMID- 22662281
TI  - Extensive self-harm scarring: successful treatment with simultaneous use of a
      single layer skin substitute and split-thickness skin graft.
AB  - OBJECTIVE: Deliberate self-harm resulting in extensive skin scarring is a
      difficult clinical problem and is commonly associated with physical and sexual
      abuse or a known history of mental illness. Immediate hospital attendance often
      addresses the acute wound and current psychological state of patients; however,
      ongoing regret of these resulting scars present a problem to the patient and
      clinician. Deliberate self-harm to the skin leaves permanent and socially
      unacceptable scars in anatomically conspicuous areas and recognizable to others.
      Therefore, the aim was to offer a treatment to change these scars to that of an
      unknown entity. METHODS: Six patients with extensive linear scars covering most
      of the forearm received surgical reconstruction. Patients were female aged
      between 18 and 47 years. Each patient had a history of psychosocial problems, and
      each had undergone psychiatric treatment. After an in-depth consultation and a
      further clinical psychological assessment, each individual was deemed suitable
      for reconstructive surgery. Scars were excised from the forearm en block,
      removing the majority of the affected area. Simultaneous use of a single layer
      skin substitute was used, covered by an autologous split-thickness skin graft.
      Negative pressure wound therapy was then applied immediately for 2 weeks after
      surgery. RESULTS: The original scars were successfully converted to a socially
      and cosmetically acceptable appearance. Postoperative infection due to negative
      pressure wound therapy failure in one patient was the only complication reported.
      CONCLUSIONS: This case series highlights the utility of an innovative treatment
      for patients with DSH scarring resulting in aesthetic, psychological, and
      functional benefits.

PMID- 22662282
TI  - Early experience with barbed sutures for abdominal closure in deep inferior
      epigastric perforator flap breast reconstruction.
AB  - OBJECTIVE: Barbed sutures have recently been introduced for closure of surgical
      incisions. These self-anchoring sutures incorporate evenly spaced barbs in a
      circumferential distribution along their length, facilitating knotless wound
      closure and even distribution of tension along the suture line. In this study, we
      evaluated postoperative complications associated with the use of unidirectional
      barbed sutures compared with standard sutures for closure of the abdominal
      incision in deep inferior epigastric perforator flap breast reconstruction.
      METHODS: A consecutive series of 142 patients undergoing deep inferior epigastric
      perforator flap breast reconstruction were identified at a single institution.
      The abdominal closure in the first 71 patients was performed using standard
      suture materials. In the subsequent 71 patients, closure was performed using
      unidirectional barbed sutures. Patient demographics, complications, procedure
      time, and costs were compared between standard and barbed suture groups. RESULTS:
      Demographic characteristics and comorbidity profiles were similar between the 2
      groups. Overall, there was a significantly higher incidence of complications in
      the standard suture group (17 vs 7 complications,P = .0423). Similar rates of
      wound infection (P = .4412), wound dehiscence (P = .4934), and seroma (P = .1157)
      were recorded in both groups. Barbed sutures were $ 15.58 more expensive than
      standard sutures. No significant difference in total length of operation was
      observed. CONCLUSION: In this study, the utility of unidirectional barbed sutures
      in deep inferior epigastric perforator flap breast reconstruction has been
      demonstrated. Barbed sutures may be useful in a broad range of plastic surgery
      procedures, not only because of their convenience but also based on favorable
      clinical outcomes.

PMID- 22662283
TI  - Umbilical transposition in functional panniculectomy of the massive weight loss
      patient: is it aesthetic or medically necessary?
AB  - BACKGROUND: We review the procedures used in panniculectomy and explore the
      necessity of umbilical transposition when adequately treating the medical and
      functional problems associated with panniculus in the massive weight loss
      patient. METHODS: Thirty-five consecutive patients with symptomatic panniculus
      after massive weight loss undergoing panniculectomy during the time period from
      November 2008 to October 2010 at Denver Health Medical Center were
      retrospectively analyzed. Inclusion criteria consisted of insurance approval for
      the panniculectomy. All patients had persistent skin problems in the lower
      abdomen. Seven patients had additional skin problems in the skin around navel
      and/or mid-abdomen. Eleven patients complained of difficulty in performing
      activities of daily living. Nine patients had a concomitant ventral hernia
      repair. RESULTS: An infraumbilical panniculectomy was adequate in treating the
      medical and functional symptoms of the abdominal region in 3 patients with no
      need for umbilical transposition. The remaining 32 patients required a different
      procedure instead of only an infraumbilical panniculectomy. Among these 32
      patients, 3 patients underwent panniculectomy with sacrifice of the umbilicus.
      Umbilical transposition following abdominal undermining was needed in the
      remaining 29 patients undergoing panniculectomy. CONCLUSIONS: Functional
      umbilical transposition was required to avoid unnatural displacement of the navel
      while treating chronic skin problems in the lower abdomen, or additional
      persistent skin problems around the navel or in the mid-abdomen, and to access
      the supraumbilical region, particularly for large ventral hernia repair during
      panniculectomy. Therefore, umbilical transposition in these cases was not
      aesthetic in nature but an integral part of achieving a functional surgical
      treatment.

PMID- 22662284
TI  - Patterns of Violence Against Women: A Latent Class Analysis.
AB  - This study examined patterns of nine types of violence against women (VAW) and
      associated mental health problems. The following self-reported, lifetime violence
      victimization was examined among 1424 employed women: (1) childhood physical
      abuse, (2) childhood sexual abuse, (3) physical abuse between parents/guardians
      during childhood, (4) psychological intimate partner violence (IPV), (5) physical
      IPV, (6) sexual IPV, (7) adult physical or sexual assault by a non-intimate
      partner, (8) physical workplace violence, and (9) psychological workplace
      violence. Latent class analysis was used to identify homogenous patterns, called
      "classes," of women's "yes/no" responses to experiencing these types of violence.
      The best model consisted of 4-classes characterized by the following
      probabilities: low violence (class 1: 63.1%), high psychological and physical IPV
      (class 2: 15.6%), high physical and psychological workplace violence (class 3:
      12.4%), and moderate to high childhood abuse (class 4: 9.0%). When compared to
      class 1 (low violence), membership in classes 2 (IPV) and 4 (childhood abuse) was
      associated with screening positive for depression in the past week at baseline
      after controlling for the influence of demographic characteristics on class
      membership. Also, when compared to class 1 (low all), membership in class 2 (IPV)
      was associated with greater odds of screening positive for posttraumatic stress
      disorder in the past month at the six month follow-up assessment. Findings
      document distinct patterns of VAW and associated proximal and distal mental
      health outcomes. Implications for interventions aimed to improve employed women's
      health are discussed.

PMID- 22662285
TI  - Bacterial infections other than spontaneous bacterial peritonitis in cirrhosis.
AB  - Cirrhotic patients are immunocompromised with a high risk of infection.
      Proinflammatory cytokines and hemodynamic circulation derangement further
      facilitate the development of serious consequences of infections. Other than
      spontaneous bacterial peritonitis, bacteremia and bacterial infections of other
      organ systems are frequently observed. Gram-negative enteric bacteria are the
      most common causative organism. Other bacterial infections, such as enterococci,
      Vibrio spp., Aeromonas spp., Clostridium spp., Listeria monocytogenes,
      Plesiomonas shigelloides and Mycobacterium tuberculosis are more prevalent and
      more virulent. Generally, intravenous third generation cephalosporins are
      recommended as empirical antibiotic therapy. Increased incidences of gram
      positive and drug-resistant organisms have been reported, particularly in
      hospital-acquired infections and in patients receiving quinolones prophylaxis.
      This review focuses upon epidemiology, microbiology, clinical features and
      treatment of infections in cirrhosis other than spontaneous bacterial
      peritonitis, including pathogen-specific and liver disease-specific issues.

PMID- 22662286
TI  - Improved cryopreservation of human hepatocytes using a new xeno free
      cryoprotectant solution.
AB  - AIM: To optimize a xeno-free cryopreservation protocol for primary human
      hepatocytes. METHODS: The demand for cryopreserved hepatocytes is increasing for
      both clinical and research purposes. Despite several hepatocyte cryopreservation
      protocols being available, improvements are urgently needed. We first compared
      controlled rate freezing to polystyrene box freezing and did not find any
      significant change between the groups. Using the polystyrene box freezing, we
      compared two xeno-free freezing solutions for freezing of primary human
      hepatocytes: a new medium (STEM-CELLBANKER, CB), which contains
      dimethylsulphoxide (DMSO) and anhydrous dextrose, both permeating and non
      permeating cryoprotectants, and the frequently used DMSO - University of
      Wisconsin (DMSO-UW) medium. The viability of the hepatocytes was assessed by the
      trypan blue exclusion method as well as a calcein-esterase based live-dead assay
      before and after cryopreservation. The function of the hepatocytes was evaluated
      before and after cryopreservation by assessing enzymatic activity of 6 major
      cytochrome P450 isoforms (CYPs): CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and
      CYP3A7. RESULTS: The new cryoprotectant combination preserved hepatocyte
      viability significantly better than the standard DMSO-UW protocol (P < 0.01).
      There was no significant difference in viability estimation between both the
      trypan blue (TB) and the Live-Dead Assay methods. There was a correlation between
      viability of fresh hepatocytes and the difference in cell viability between CB
      and DMSO protocols (r(2) = 0.69) using the TB method. However, due to high within
      group variability in the activities of the major CYPs, any statistical between
      group differences were precluded. Cryopreservation of human hepatocytes using the
      cryoprotectant combination was a simple and xeno-free procedure yielding better
      hepatocyte viability. Thus, it may be a better alternative to the standard DMSO
      UW protocol. Estimating CYP activities did not seem to be a relevant way to
      compare hepatocyte function between different groups due to high normal
      variability between different liver samples. CONCLUSION: The cryoprotectant
      combination may be a better alternative to the standard DMSO-UW protocol in
      primary human hepatocyte cryopreservation.

PMID- 22662287
TI  - Discovery of Novel Small Molecule Mer Kinase Inhibitors for the Treatment of
      Pediatric Acute Lymphoblastic Leukemia.
AB  - Ectopic Mer expression promotes pro-survival signaling and contributes to
      leukemogenesis and chemoresistance in childhood acute lymphoblastic leukemia
      (ALL). Consequently, Mer kinase inhibitors may promote leukemic cell death and
      further act as chemosensitizers increasing efficacy and reducing toxicities of
      current ALL regimens. We have applied a structure-based design approach to
      discover novel small molecule Mer kinase inhibitors. Several pyrazolopyrimidine
      derivatives effectively inhibit Mer kinase activity at sub-nanomolar
      concentrations. Furthermore, the lead compound shows a promising selectivity
      profile against a panel of 72 kinases and has excellent pharmacokinetic
      properties. We also describe the crystal structure of the complex between the
      lead compound and Mer, opening new opportunities for further optimization and new
      template design.

PMID- 22662288
TI  - HIV-1 Integrase Inhibitor-Inspired Antibacterials Targeting Isoprenoid
      Biosynthesis.
AB  - We report the discovery of antibacterial leads, keto- and diketo-acids, targeting
      two prenyl transferases: undecaprenyl diphosphate synthase (UPPS) and
      dehydrosqualene synthase (CrtM). The leads were suggested by the observation that
      keto- and diketo-acids bind to the active site Mg(2+)/Asp domain in HIV-1
      integrase, and similar domains are present in prenyl transferases. We report the
      x-ray crystallographic structures of one diketo-acid and one keto-acid bound to
      CrtM, which supports the Mg(2+) binding hypothesis, together with the x-ray
      structure of one diketo-acid bound to UPPS. In all cases, the inhibitors bind to
      a farnesyl diphosphate substrate-binding site. Compound 45 had cell growth
      inhibition MIC(90) values of ~250-500 ng/mL against S. aureus, 500 ng/mL against
      Bacillus anthracis, 4 MUg/mL against Listeria monocytogenes and Enterococcus
      faecium, and 1 MUg/mL against Streptococcus pyogenes M1, but very little activity
      against E. coli (DH5alpha, K12) or human cell lines.

PMID- 22662291
TI  - Enhancing the in vitro Fe(2+) bio-accessibility using ascorbate and cold-set whey
      protein gel particles.
AB  - This paper investigates the possibility for iron fortification of food using a
      new preparation method for protein gel particles in which iron is entrapped in
      the presence of ascorbate using cold-set gelation. The effect of ascorbate on the
      iron-induced cold-set gelation process of whey protein was studied in order to
      optimize the ratio of iron/ascorbate. Subsequently, the effect of ascorbate on
      iron bio-accessibility was assessed in vitro. Rheology was used to study the
      protein gel formation, and the stability of the gel particles was determined by
      measuring the iron and protein content at different pH. In vitro studies were
      performed with the TNO Intestinal Model (TIM). Ascorbate appeared to affect the
      gel formation process and increased the gel strength of the iron-induced cold-set
      gels at specific iron/ascorbate ratio. With the Fe-protein gel particles being
      stable at a broad pH range, the release of iron from the particles was studied as
      a function of time. The low release of iron indicated a good encapsulation
      efficiency and the capability of whey protein to keep iron bound at different
      conditions (pH and presence of calcium). Results obtained with the TIM showed
      that ascorbate, when added to the protein gel particles, was very successful in
      enhancing the recovery and absorption of iron. The in vitro Fe(2+) bio
      accessibility in the presence of ascorbate in iron-protein particles increased
      from 10% to almost 80%. This suggests that the concept of using protein particles
      with iron and ascorbate can effectively be used to fortify food products with
      iron for human consumption.

PMID- 22662290
TI  - A highly sensitive sandwich ELISA for the determination of glycomacropeptide to
      detect liquid whey in raw milk.
AB  - Milk processing industries and distributors have problems with adulteration of
      liquid milk by the addition of bovine cheese whey. Recently, the detection of
      fraudulent manipulation of milk with whey has focused on the identification of
      glycomacropeptide (GMP). Current non-immunological methods to detect GMP in dairy
      products are expensive and time-consuming or have low sensitivity. In this study,
      a novel sandwich enzyme-linked immunosorbent assay (ELISA) for the detection and
      quantification of whey in raw milk was developed, using a polyclonal rabbit anti
      GMP antibody. Calibration curves were constructed by analyzing raw milk standards
      containing different known concentrations of liquid cheese whey (0.02-20%). The
      method had a detection limit of 0.047% (v/v) and a quantification limit of 0.14%
      (v/v). The antibody showed high specificity and no cross-reaction with milk
      components (other than kappa-casein) and was successful in detecting GMP in dairy
      commercial products. The recovery ratio was between 95.62% and 113.88% for all
      matrices tested. The intra-assay and interassay coefficients of variation were
      <6% and <7%, respectively. Finally, it can be stored for 3 months in the form of
      a ready-to-use kit, while maintaining its accuracy and reproducibility.

PMID- 22662289
TI  - Proton Coupled Electron Transfer and Redox Active Tyrosines: Structure and
      Function of the Tyrosyl Radicals in Ribonucleotide Reductase and Photosystem II.
AB  - Proton coupled electron transfer (PCET) reactions are important in many
      biological processes. Tyrosine oxidation/reduction can play a critical role in
      facilitating these reactions. Two examples are photosystem II (PSII) and
      ribonucleotide reductase (RNR). RNR is essential in DNA synthesis in all
      organisms. In E. coli RNR, a tyrosyl radical, Y122(*), is required as a radical
      initiator. Photosystem II (PSII) generates molecular oxygen from water. In PSII,
      an essential tyrosyl radical, YZ(*), oxidizes the oxygen evolving center.
      However, the mechanisms, by which the extraordinary oxidizing power of the
      tyrosyl radical is controlled, are not well understood. This is due to the
      difficulty in acquiring high-resolution structural information about the radical
      state. Spectroscopic approaches, such as EPR and UV resonance Raman (UVRR), can
      give new information. Here, we discuss EPR studies of PCET and the PSII YZ
      radical. We also present UVRR results, which support the conclusion that Y122
      undergoes an alteration in ring and backbone dihedral angle when it is oxidized.
      This conformational change results in a loss of hydrogen bonding to the phenolic
      oxygen. Our analysis suggests that access of water is an important factor in
      determining tyrosyl radical lifetime and function. TOC graphic.

PMID- 22662292
TI  - Self-Deception, Delusion and the Boundaries of Folk Psychology.
AB  - To what extent do self-deception and delusion overlap? In this paper we argue
      that both self-deception and delusions can be understood in folk-psychological
      terms. "Motivated" delusions, just like self-deception, can be described as
      beliefs driven by personal interests. If self-deception can be understood folk
      psychologically because of its motivational component, so can motivated
      delusions. Non-motivated delusions also fit (to a large extent) the folk
      psychological notion of belief, since they can be described as hypotheses one
      endorses when attempting to make sense of unusual and powerful experiences. We
      suggest that there is continuity between the epistemic irrationality manifested
      in self-deception and in delusion.

PMID- 22662293
TI  - Pathobiology of obesity and osteoarthritis: integrating biomechanics and
      inflammation.
AB  - Obesity is a significant risk factor for developing osteoarthritis in weight
      bearing and non-weight-bearing joints. Although the pathogenesis of obesity
      associated osteoarthritis is not completely understood, recent studies indicate
      that pro-inflammatory metabolic factors contribute to an increase in
      osteoarthritis risk. Adipose tissue, and in particular infrapatellar fat, is a
      local source of pro-inflammatory mediators that are increased with obesity and
      have been shown to increase cartilage degradation in cell and tissue culture
      models. One adipokine in particular, leptin, may be a critical mediator of
      obesity-associated osteoarthritis via synergistic actions with other inflammatory
      cytokines. Biomechanical factors may also increase the risk of osteoarthritis by
      activating cellular inflammation and promoting oxidative stress. However, some
      types of biomechanical stimulation, such as physiologic cyclic loading, inhibit
      inflammation and protect against cartilage degradation. A high percentage of
      obese individuals with knee osteoarthritis are sedentary, suggesting that a lack
      of physical activity may increase the susceptibility to inflammation. A more
      comprehensive approach to understanding how obesity alters daily biomechanical
      exposures within joint tissues may provide new insight into the protective and
      damaging effects of biomechanical factors on inflammation in osteoarthritis.

PMID- 22662294
TI  - Recent evolution of cruciate ligament surgery of the knee.

PMID- 22662296
TI  - The conversion rate of bipolar hemiarthroplasty after a hip fracture to a total
      hip arthroplasty.
AB  - BACKGROUND: Bipolar hip hemiarthroplasty is used in the management of fractures
      of the proximal femur. The dual articulation is cited as advantageous in
      comparison to unipolar prostheses as it decreases acetabular erosion, has a lower
      dislocation rates and is easier to convert to a total hip arthroplasty (THA)
      should the need arise. However, these claims are debatable. Our study examines
      the rate of conversion of the bipolar hemiarthroplasty to THA and the
      justification for using it on the basis of future conversion to THA. METHODS: All
      cases of bipolar hemiarthroplasty performed in our unit for hip fractures over a
      9-year period (1999-2007) were reviewed. Medical notes and radiographs of all
      patients were reviewed, and all surviving patients that were contactable received
      a telephone follow-up. RESULTS: Of all 164 patients reviewed with a minimum of 1
      year from date of surgery, 4 patients had undergone a conversion of their bipolar
      prosthesis to THA. Three conversions were performed for infection, dislocation,
      and fracture. Only one (0.6%) conversion was performed for groin pain.
      CONCLUSIONS: Our study show that bipolar hemiarthroplasties for hip fractures
      have a low conversion rate to THAs and this is comparable to the published
      conversion rate of unipolar hemiarthroplasties.

PMID- 22662295
TI  - Modern interpretation of giant cell tumor of bone: predominantly osteoclastogenic
      stromal tumor.
AB  - Owing to striking features of numerous multinucleated cells and bone destruction,
      giant cell tumor (GCT) of bone, often called as osteoclastoma, has drawn major
      attractions from orthopaedic surgeons, pathologists, and radiologists. The name
      GCT or osteoclastoma gives a false impression of a tumor comprising of
      proliferating osteoclasts or osteoclast precursors. The underlying mechanisms for
      excessive osteoclastogenesis are intriguing and GCT has served as an exciting
      disease model representing a paradigm of osteoclastogenesis for bone biologists.
      The modern interpretation of GCT is predominantly osteoclastogenic stromal cell
      tumors of mesenchymal origin. A diverse array of inflammatory cytokines and
      chemokines disrupts osteoblastic differentiation and promotes the formation of
      excessive multi-nucleated osteoclastic cells. Pro-osteoclastogenic cytokines such
      as receptor activator of nuclear factor kappa-B ligand (RANKL), interleukin (IL)
      6, and tumor necrosis factor (TNF) as well as monocyte-recruiting chemokines such
      as stromal cell-derived factor-1 (SDF-1) and monocyte chemoattractant protein
      (MCP)-1 participate in unfavorable osteoclastogenesis and bone destruction. This
      model represents a self-sufficient osteoclastogenic paracrine loop in a localized
      area. Consistent with this paradigm, a recombinant RANK-Fc protein and
      bisphosphonates are currently being tried for GCT treatment in addition to
      surgical excision and conventional topical adjuvant therapies.

PMID- 22662297
TI  - Total knee arthroplasty in hemophiliacs: gains in range of motion realized beyond
      twelve months postoperatively.
AB  - BACKGROUND: Hemophiliacs have extrinsic tightness from quadriceps and flexion
      contractures. We sought to examine the effect of a focused physical therapy
      regimen geared to hemophilic total knee arthroplasty. METHODS: Twenty-four knees
      undergoing intensive hemophiliac-specific physical therapy after total knee
      arthroplasty, at an average age of 46 years, were followed to an average 50
      months. RESULTS: For all patients, flexion contracture improved from -10.5
      degrees preoperatively to -5.1 degrees at final follow-up (p = 0.02). Knees with
      preoperative flexion less than 90 degrees were compared to knees with
      preoperative flexion greater than 90 degrees. Patients with preoperative flexion
      less than 90 degrees experienced improved flexion (p = 0.02), along with improved
      arc range of motion (ROM) and decreased flexion contracture. For those patients
      with specific twelve-month and final follow-up data points, there was a
      significant gain in flexion between twelve months and final follow-up (p = 0.02).
      CONCLUSIONS: Hemophiliacs with the poorest flexion benefited most from focused
      quadriceps stretching to a more functional length, with gains not usually seen in
      the osteoarthritic population. This data may challenge traditional views that ROM
      gains are not expected beyond 12-18 months.

PMID- 22662298
TI  - Intra-articular patterns of bucket handle meniscal tears and its relation to
      reducibility.
AB  - BACKGROUND: The purpose of this study was to assess the intra-articular patterns
      in the rotational deformities of bucket handle meniscal tears (BHMTs) based on
      arthroscopic findings and their clinical relevance. METHODS: From 2004 to 2009,
      42 patients with a BHMT diagnosed by magnetic resonance imaging underwent
      arthroscopic surgery. The arthroscopic data (all procedures were recorded) were
      evaluated retrospectively, and BHMTs were classified according to the rotational
      directions of centrally displaced fragments. To assess the reliability of the
      agreement in this classification, 2 orthopedic surgeons re-classified BHMTs, 1
      week after first trial. Intra- and interobserver reliabilities were assessed
      using kappa statistics. In addition, we address specific tear patterns,
      associated anterior cruciate ligament injury, medio-lateral difference,
      reducibility, chronicity, and reparability. RESULTS: Most of the tears could be
      categorized into one of 3 morphologic patterns. Of the tears, 4.8% could not be
      categorized. BHMTs were classified, based on the rotational directions of
      centrally displaced fragments, as follows; the upward rotation group (type 1),
      the downward rotation group (type 2) and the reverse group (type 3). The most
      common intra-articular pattern was type 1 (29 patients, 69%). The occurrence of
      the other patterns was: type 2 in 7 patients (16.7%), type 3 in 4 patients
      (9.5%); we were not able to make a classification of type in 2 patients (4.8%).
      Intra-observer reliability was 0.86 in terms of kappa statistics, which implies
      almost perfect agreement. Mean interobserver reliability (0.73) showed
      substantial agreement. Type 1 and 2 tears were easily reduced, whereas all type 3
      tears (4/4) needed additional procedures to achieve reduction. CONCLUSIONS: Based
      on arthroscopic findings, we describe a comprehensive BHMT classification scheme
      that encompasses 95.2% of all tears. Tear type was correlated with reducibility.

PMID- 22662299
TI  - Avulsion fracture of the calcaneal tuberosity: classification and its
      characteristics.
AB  - BACKGROUND: Not much is known regarding avulsion fractures of the calcaneal
      tuberosity. We propose a modified classification scheme that presents the four
      types of calcaneal avulsion fracture as described by surgical and magnetic
      resonance imaging (MRI) findings, and evaluation of their specific features.
      METHODS: Out of 764 cases of calcaneal fractures, we examined 20 cases (2.6%)
      that involved the tuberosity of the calcaneus. Each case was classified depending
      on the avulsed fracture patterns as follows; type I is a 'simple extra-articular
      avulsion' fracture, type II is the 'beak' fracture, type III is an infrabursal
      avulsion fracture from the middle third of the posterior tuberosity, and finally
      in type IV there is the 'beak', but a small triangular fragment is separated from
      the upper border of the tuberosity. We examined the features of each avulsed type
      according to several criteria including patient age, gender, anatomical variances
      of the Achilles tendon, the fibers involved and the mechanism of injury. RESULTS:
      The type I fracture (8/20 cases) was the most common and likely to occur in
      elderly women. However, in other types, they were more common in relatively
      younger male patients. Type I were usually caused due to an accidental trip
      causing a fall by the patient. However, the dominant cause of type II (5/20
      cases) fractures a direct blow or hit directly to the bone. Type III (4/20 cases)
      and IV (3/20 cases) fractures were likely to occur due to falling. All fibers
      within the Achilles tendon are involved in both type I and II fractures. However,
      only the superficial fibers are involved in type III fractures, whereas the deep
      fibers are involved in type IV fractures. CONCLUSIONS: The avulsion patterns of
      the calcaneal tuberosity fractures are the result of several factors including
      the bony density level, the mechanism of injury and the fibers of the Achilles
      tendon that transmit the force. Accurate diagnosis of type III and IV is
      dependant on MRI technology to confirm the specific location of the injury and
      provide proper patient treatment therapeutics.

PMID- 22662300
TI  - Early results of one-stage correction for hip instability in cerebral palsy.
AB  - BACKGROUND: We evaluated the clinical and radiological results of one-stage
      correction for cerebral palsy patients. METHODS: We reviewed clinical outcomes
      and radiologic indices of 32 dysplastic hips in 23 children with cerebral palsy
      (13 males, 10 females; mean age, 8.6 years). Ten hips had dislocation, while 22
      had subluxation. Preoperative Gross Motor Function Classification System (GMFCS)
      scores of the patients were as follows; level V (13 patients), level IV (9), and
      level III (1). Acetabular deficiency was anterior in 5 hips, superolateral in 7,
      posterior in 11 and mixed in 9, according to 3 dimensional computed tomography.
      The combined surgery included open reduction of the femoral head, release of
      contracted muscles, femoral shortening varus derotation osteotomy and the
      modified Dega osteotomy. Hip range of motion, GMFCS level, acetabular index,
      center-edge angle and migration percentage were measured before and after
      surgery. The mean follow-up period was 28.1 months. RESULTS: Hip abduction
      (median, 40 degrees ), sitting comfort and GMFCS level were improved after
      surgery, and pain was decreased. There were two cases of femoral head avascular
      necrosis, but no infection, nonunion, resubluxation or redislocation. All
      radiologic indices showed improvement after surgery. CONCLUSIONS: A single event
      multilevel surgery including soft tissue, pelvic and femoral side correction is
      effective in treating spastic dislocation of the hip in cerebral palsy.

PMID- 22662301
TI  - Pitfalls and important issues in testing reliability using intraclass correlation
      coefficients in orthopaedic research.
AB  - BACKGROUND: Intra-class correlation coefficients (ICCs) provide a statistical
      means of testing the reliability. However, their interpretation is not well
      documented in the orthopedic field. The purpose of this study was to investigate
      the use of ICCs in the orthopedic literature and to demonstrate pitfalls
      regarding their use. METHODS: First, orthopedic articles that used ICCs were
      retrieved from the Pubmed database, and journal demography, ICC models and
      concurrent statistics used were evaluated. Second, reliability test was performed
      on three common physical examinations in cerebral palsy, namely, the Thomas test,
      the Staheli test, and popliteal angle measurement. Thirty patients were assessed
      by three orthopedic surgeons to explore the statistical methods testing
      reliability. Third, the factors affecting the ICC values were examined by
      simulating the data sets based on the physical examination data where the ranges,
      slopes, and interobserver variability were modified. RESULTS: Of the 92
      orthopedic articles identified, 58 articles (63%) did not clarify the ICC model
      used, and only 5 articles (5%) described all models, types, and measures. In
      reliability testing, although the popliteal angle showed a larger mean absolute
      difference than the Thomas test and the Staheli test, the ICC of popliteal angle
      was higher, which was believed to be contrary to the context of measurement. In
      addition, the ICC values were affected by the model, type, and measures used. In
      simulated data sets, the ICC showed higher values when the range of data sets
      were larger, the slopes of the data sets were parallel, and the interobserver
      variability was smaller. CONCLUSIONS: Care should be taken when interpreting the
      absolute ICC values, i.e., a higher ICC does not necessarily mean less
      variability because the ICC values can also be affected by various factors. The
      authors recommend that researchers clarify ICC models used and ICC values are
      interpreted in the context of measurement.

PMID- 22662302
TI  - Management of proximal phalangeal fractures of the hand using finger nail
      traction and a digital splint: a prospective study of 43 cases.
AB  - BACKGROUND: Proximal phalangeal fractures are common fractures of the hand. The
      fractures are difficult to treat because of vicinity of two important joints and
      crossing long tendons. The purpose of this study was to evaluate the efficacy of
      nail traction technique in the management of proximal phalangeal fractures of the
      hand. METHODS: Patients (n=43) with proximal phalangeal fractures were treated by
      nail traction and evaluated prospectively. We assessed all the patients at the
      time of presentation and then followed a standard protocol for recruiting
      patients. After application of nail traction, the patients were initially
      assessed at 12th day. The outcome measures included post reduction radiographic
      evaluation and total active motion (TAM) in finger at the final follow-up
      appointment. All the patients were followed for one year. RESULTS: The post
      reduction X-ray evaluation showed good reduction in 33 cases, fair reduction in 8
      and poor reduction in 2 cases. At final assessment, 35 patients had good TAM
      score, six had fair and two had poor TAM score. Complications were noted in two
      patients and these included pressure necrosis in palm and stiffness in proximal
      interphalangeal joint. CONCLUSIONS: The results of this prospective study show
      that with careful selection of patients, nail traction seems to be simple, safe
      and effective technique for managing proximal phalangeal fractures.

PMID- 22662303
TI  - Augmentation with transcortical wiring of an onlay-type prosthesis for a
      deficient patella during revision total knee arthroplasty.
AB  - The management of patellae with a severe bony deficiency during revision total
      knee arthroplasty is a challenging problem. However, using a technique of
      augmentation with transcortical wiring of an onlay-type prosthesis allowed the
      authors to revise a deficient patellae successfully. After making the decision to
      revise the existing patellar component, the procedure was found to be technically
      straightforward. Furthermore, the procedure does not require sophisticated
      instruments, only an onlay-type prosthesis, cement and wires. This technique
      entails fixing wires to the three pegs of the patellar component, passing the
      wires through drill holes in the anterior cortex and, after compression of a
      cemented prosthesis, augmenting the fixation by twisting the wires anteriorly. We
      believe that stable fixation and painless articulation will be obtained with the
      described technique for deficient patellae.

PMID- 22662304
TI  - Mucoid degeneration of both ACL and PCL.
AB  - Unlike meniscal tears and chondral defects, the mucoid degeneration of the
      anterior cruciate ligament (ACL) is a rare cause of knee pain and there have been
      no case reports of mucoid degeneration of both the ACL and the posterior cruciate
      ligament (PCL). A 48-year-old-male patient presented with knee pain and
      limitation of motion. The patient's magnetic resonance imaging, arthroscopic
      findings, and pathologic diagnosis confirmed a clinical diagnosis of mucoid
      degeneration of both the ACL and the PCL. The symptoms disappeared after
      arthroscopic partial excision of the ACL and PCL.

PMID- 22662305
TI  - Could we prevent displacing the undisplaced fracture neck of femur? To the
      editor.

PMID- 22662306
TI  - Summary Description of 24 Cases of Neonatal Malaria Seen at a Tertiary Health
      Center in Nigeria.
AB  - OBJECTIVE: Neonatal malaria is a serious cause of morbidity and mortality in sub
      Saharan Africa. Diagnosis of neonatal malaria is difficult because of the
      similarity in clinical presentation with other neonatal infections. This study
      aim to highlight the clinical presentations and high mortality still associated
      with neonatal malaria.  METHODS: Twenty four out of 41 neonates seen during a 6
      months period were studied. Gestational age, age at presentation, birth weight
      and other clinical symptoms were documented. Questionnaires were used to collect
      pertinent pregnancy and perinatal history from the mothers. Data was analyzed
      using SPSS v18 and results expressed in tables using means, frequencies and
      percentages.  FINDINGS: All 24 neonates, 50% of whom were males, had a positive
      smear for malaria parasite. 29.2% were preterm, 17(70.8%) had congenital malaria,
      18(75.0%) mothers used intermittent preventive treatment (IPT) of malaria
      prophylaxis in the index pregnancy and 1(4.2%) mother had HIV in pregnancy. Fever
      was the principal presenting symptom and 83.0% responded to treatment with
      amodiaquine.  CONCLUSION: Neonatal malaria is still an important cause of
      mortality, a more effective malaria prophylaxis program and routine malaria
      parasite screening for neonates is recommended.

PMID- 22662307
TI  - A simple method for the synthesis of hyaluronic acid coated magnetic
      nanoparticles for highly efficient cell labelling and in vivo imaging.
AB  - Highly stable colloidal hyaluronic acid coated magnetic nano-particles were
      prepared via a ligand exchange method. These particles exhibited excellent cell
      labeling efficiencies and superior potential as MRI contrast agents, which are
      useful to target tumor cells expressing hyaluronic acid receptors such as CD44.

PMID- 22662308
TI  - A PEPTIDE UNCOUPLING CRMP-2 FROM THE PRESYNAPTIC Ca(2+) CHANNEL COMPLEX
      DEMONSTRATES EFFICACY IN ANIMAL MODELS OF MIGRAINE AND AIDS THERAPY-INDUCED
      NEUROPATHY.
AB  - Biological, genetic, and clinical data provide compelling proof for N-type
      voltage-gated calcium channels (CaV2.2) as therapeutic targets for chronic pain.
      While decreasing channel function is ultimately anti-nociceptive, directly
      targeting the channel can lead to multiple adverse effects. Targeting regulators
      of channel activity may facilitate improved analgesic properties associated with
      channel block and afford a broader therapeutic window. Towards this end, we
      recently identified a short peptide, designated CBD3, derived from collapsin
      response mediator protein 2 (CRMP-2) that suppressed inflammatory and neuropathic
      hypersensitivity by inhibiting CRMP-2 binding to CaV2.2 [Brittain et al., Nature
      Medicine 17:822-829 (2011)]. Rodents administered CBD3 intraperitoneally, fused
      to the HIV TAT protein cell penetrating domain, exhibited antinociception lasting
      ~4 hours highlighting potential instability, limited oral bioavailability, and/or
      rapid elimination of peptide. This report focuses on improving upon the parental
      CBD3 peptide. Using SPOTScan analysis of synthetic versions of the parental CBD3
      peptide, we identified peptides harboring single amino acid mutations that bound
      with greater affinity to CaV2.2. One such peptide, harboring a phenylalanine
      instead of glycine (G14F), was tested in rodent models of migraine and
      neuropathic pain. In vivo laser Doppler blood flowmetry measure of capsaicin
      induced meningeal vascular responses related to headache pain was almost
      completely suppressed by dural application of the G14F peptide. The G14F mutant
      peptide, administered intraperitoneally, also exhibited greater antinociception
      in Stavudine (2'-3'-didehydro-2'-3'-dideoxythymidine (d4T)/Zerit(r)) model of
      AIDS therapy-induced peripheral neuropathy compared to the parent CBD3 peptide.
      These results demonstrate the patent translational value of small biologic drugs
      targeting CaV2.2 for management of clinical pain.

PMID- 22662309
TI  - Metabotropic glutamate receptor-mediated signaling in neuroglia.
AB  - Metabotropic glutamate (mGlu) receptors are G-protein-coupled receptors, which
      include eight subtypes that have been classified into three groups (I-III) based
      upon sequence homology, signal transduction mechanism and pharmacological
      profile. Although most studied with regard to neuronal function and modulation,
      mGlu receptors are also expressed by neuroglia-including astrocytes, microglia
      and oligodendrocytes. Activation of mGlu receptors on neuroglia under both
      physiologic and pathophysiologic conditions mediates numerous actions that are
      essential for intrinsic glial cell function, as well as for glial-neuronal
      interactions. Astrocyte mGlu receptors play important physiological roles in
      regulating neurotransmission and maintaining neuronal homeostasis. However, mGlu
      receptors on astrocytes and microglia also serve to modulate cell death and
      neurological function in a variety of pathophysiological conditions such as acute
      and chronic neurodegenerative disorders. The latter effects are complex and bi
      directional, depending on which mGlu receptor sub-types are activated.

PMID- 22662310
TI  - mGlu Receptors and Cancerous Growth.
AB  - G-protein coupled receptors (GPCR) represent a class of therapeutic targets that
      have been widely exploited for drug designs and development. Metabotropic
      glutamate receptors (mGluRs) belong to Class C GPCRs and are predominantly
      involved in maintaining cellular homeostasis in the central nervous system (CNS).
      The surprising accumulating evidence suggesting other functional roles of mGluRs
      in human malignancies in addition to synaptic transmission has presented
      intriguing possibilities to make mGluRs putative novel targets for human cancers.
      Since our group first described the aberrant expression of mGluR1 as the driving
      force in melanomagenesis in transgenic mouse models, other subtypes of mGluRs
      have been implicated in the pathogenesis of various cancer types such as
      malignant gliomas and medulloblastomas. As such, increased efforts have been
      generated to elucidate the mechanisms by which mGluRs confer oncogenic
      potentials. Current knowledge on the participation of various mGluRs in several
      human cancers suggests that mGluRs are "druggable" members of the GPCR
      superfamily and their oncogenic implications in cancer, so further understanding
      on anti-mGluR strategies will be beneficial.

PMID- 22662311
TI  - Function of Proton Channels in Lung Epithelia.
AB  - The properties of the voltage-dependent H(+) channel have been studied in lung
      epithelial cells for many years, and recently HVCN1 mRNA expression has been
      linked directly to H(+) channel function in lung epithelium. The H(+) channel is
      activated by strong membrane depolarization, intracellular acidity, or
      extracellular alkalinity. Early on it was noted that these are surprising
      physiological channel characteristics when considering that lung epithelial cells
      have rather stable membrane potentials and a well pH-buffered intracellular
      milieu. This raised the question under which conditions the H(+) channel is
      active in lung epithelium and what is its physiological function there. Current
      understanding of the HVCN1 H(+) channel in lung epithelial acid secretion, its
      activation by an alkaline mucosal extracellular pH, and its role in the
      regulation of the mucosal pH of the lung has resulted in a model of mucosal pH
      regulation based on the parallel function of the HVCN1 H(+) channel and the CFTR
      HCO(3) (-) channel, which suggests that HVCN1 is a critical factor that maintains
      a neutral surface pH in the lung.

PMID- 22662313
TI  - Role of purinergic P2X receptors in the control of liver homeostasis.
AB  - It is now accepted that extracellular ATP and other nucleotides are potent
      signaling molecules, akin to neurotransmitters, hormones and lipid mediators. In
      the liver, several clues support a significant role for extracellular ATP-induced
      signaling pathways in the control of tissue homeostasis. First, ATP and other
      nucleotides are physiologically detected in extracellular fluids within the
      liver, including sinusoidal blood and intraductular bile, in various mammalian
      species including human and rodents. Moreover, finely tuned mechanisms of ATP
      release by different liver cell types have been described, under physiological
      cellular changes. In addition, most hepatic cells constitutively express, at the
      membrane level, several ATP-metabolizing ectoenzymes and ATP-sensitive receptors
      that modulate and transduce these mediator signals respectively. Finally, hepatic
      cells also express numerous membrane transporters that actively contribute to
      purinergic salvage pathways. Once released in the extracellular medium,
      unmetabolised ATP molecules can bind to purinergic P2X and P2Y receptors, and
      subsequently trigger various intracellular signal transduction pathways
      collectively referred to as purinergic signaling. In the liver, purinergic
      signaling has been shown to regulate key basic cellular functions, such as
      glucose/lipid metabolism, protein synthesis and ionic secretion, and homeostatic
      processes, such as cell cycle, inflammatory response and immunity. Whilst the
      functional relevance of P2Y receptors in liver physiology has been well
      documented, limited information is available regarding the potential role of
      hepatic P2X receptors in the modulation of liver homeostasis.

PMID- 22662312
TI  - mGlu receptors and drug addiction.
AB  - Historically, brain catecholamine systems have been the primary focus of studies
      examining the neural substrates of drug addiction. In the past two decades,
      however, a wealth of evidence has accumulated indicating a pivotal role for
      glutamatergic neurotransmission in mediating addictive behaviors as well as long
      term neuroplasticity associated with chronic drug use. As a result, there has
      been increased interest in developing glutamate-based therapies for the treatment
      of addictive disorders. Metabotropic glutamate (mGlu) receptors are classified
      into subcategories designated as Group I (mGlu1 and mGlu5), Group II (mGlu2 and
      mGlu3), and Group III (mGlu4, mGlu6, mGlu7, and mGlu8), and have received a great
      deal of attention due to their mediation of slower modulatory excitatory
      neurotransmission. Pharmacological ligands targeting these receptors have
      demonstrated reduced incidences of excitotoxicity or severe adverse side effects
      as compared to those targeting ionotropic glutamate (iGlu) receptors. Behavioral
      genetic and pharmacological studies have explored the role of individual mGlu
      receptor subtypes in regulating various addiction-related behaviours and several
      mGlu receptor ligands have been the subject of clinical testing for other medical
      conditions.

PMID- 22662315
TI  - Impaired dendritic expression and plasticity of h-channels in the fmr1(-/y) mouse
      model of fragile X syndrome.
AB  - Despite extensive research into both synaptic and morphological changes,
      surprisingly little is known about dendritic function in fragile X syndrome
      (FXS). We found that the dendritic input resistance of CA1 neurons was
      significantly lower in fmr1(-/y) versus wild-type mice. Consistent with elevated
      dendritic I(h), voltage sag, rebound, and resonance frequency were significantly
      higher and temporal summation was lower in the dendrites of fmr1(-/y) mice.
      Dendritic expression of the h-channel subunit HCN1, but not HCN2, was higher in
      the CA1 region of fmr1(-/y) mice. Interestingly, whereas mGluR-mediated
      persistent decreases in I(h) occurred in both wildtype and fmr1(-/y) mice,
      persistent increases in I(h) that occurred after LTP induction in wild-type mice
      were absent in fmr1(-/y) mice. Thus, chronic upregulation of dendritic I(h) in
      conjunction with impairment of homeostatic h-channel plasticity represents a
      dendritic channelopathy in this model of mental retardation and may provide a
      mechanism for the cognitive impairment associated with FXS.

PMID- 22662316
TI  - Toward maximizing immunotherapy in metastatic castration-resistant prostate
      cancer - rationale for combinatorial approaches using chemotherapy.
AB  - Prostate cancer is particularly suited for active immunotherapy because of the
      expression of a distinctive number of antigens which are overexpressed on
      prostate cancer cells and cell lines. There is evidence in this disease that
      tumors promote immune tolerance starting early in the disease course. As such,
      chemotherapy, by suppressing tumors and activating immune system homeostatic
      mechanisms, may help overcome this tumor-induced immune tolerance. Sipuleucel-T
      which has recently been approved in the US, is an autologous cellular product
      immunotherapy that induces immune activity likely through activation of dendritic
      cells. This was associated with a survival benefit in the absence of significant
      toxicity. However, a post hoc analysis of phase III trial participants found a
      substantial survival benefit to receiving docetaxel some months after sipuleucel
      T. However, another phase III immunotherapy trial combining a prostate cancer
      therapeutic vaccine GVAX plus docetaxel versus standard docetaxel therapy in
      advanced prostate cancer, observed a lower overall survival with the vaccine
      regimen. These trials highlight major unresolved questions concerning the optimum
      choice, dosing, and timing of chemotherapy relative to active immunotherapy and
      the overall merits of considering this approach. The ideal treatment approach
      remains unclear; advances in biomarker validation and trial design may likely
      improve our ability to assess biologic benefit irrespective of the development of
      true antitumor immunity.

PMID- 22662314
TI  - Developmental diversity of amphibians.
AB  - The current model amphibian, Xenopus laevis, develops rapidly in water to a
      tadpole which metamorphoses into a frog. Many amphibians deviate from the X.
      laevis developmental pattern. Among other adaptations, their embryos develop in
      foam nests on land or in pouches on their mother's back or on a leaf guarded by a
      parent. The diversity of developmental patterns includes multinucleated
      oogenesis, lack of RNA localization, huge non-pigmented eggs, and asynchronous,
      irregular early cleavages. Variations in patterns of gastrulation highlight the
      modularity of this critical developmental period. Many species have eliminated
      the larva or tadpole and directly develop to the adult. The wealth of
      developmental diversity among amphibians coupled with the wealth of mechanistic
      information from X. laevis permit comparisons that provide deeper insights into
      developmental processes.

PMID- 22662318
TI  - The impact of peroxisomes on cellular aging and death.
AB  - Peroxisomes are ubiquitous eukaryotic organelles, which perform a plethora of
      functions including hydrogen peroxide metabolism and beta-oxidation of fatty
      acids. Reactive oxygen species produced by peroxisomes are a major contributing
      factor to cellular oxidative stress, which is supposed to significantly
      accelerate aging and cell death according to the free radical theory of aging.
      However, relative to mitochondria, the role of the other oxidative organelles,
      the peroxisomes, in these degenerative pathways has not been extensively
      investigated. In this contribution we discuss our current knowledge on the role
      of peroxisomes in aging and cell death, with focus on studies performed in yeast.

PMID- 22662317
TI  - Differential Expression of Chemokine Receptors and their Roles in Cancer Imaging.
AB  - Chemokine/chemokine receptor interactions play diverse roles in cell migration
      and homeostasis. Emerging evidence suggests that cancer cells co-opt chemokine
      networks for survival, proliferation, immune evasion, and metastasis. Most of the
      chemokine receptors are reported to be involved in tumor progression. Given their
      extensive implication in cancer progression, several chemokine receptor/ligand
      axes are considered as potential therapeutic targets. This review provides a
      survey of chemokine receptor expression in cancer and evaluates the potential of
      chemokine receptor imaging as a tool for molecular characterization of cancer.

PMID- 22662320
TI  - The first European interdisciplinary ewing sarcoma research summit.
AB  - The European Network for Cancer Research in Children and Adolescents (ENCCA)
      provides an interaction platform for stakeholders in research and care of
      children with cancer. Among ENCCA objectives is the establishment of biology
      based prioritization mechanisms for the selection of innovative targets, drugs,
      and prognostic markers for validation in clinical trials. Specifically for
      sarcomas, there is a burning need for novel treatment options, since current
      chemotherapeutic treatment protocols have met their limits. This is most obvious
      for metastatic Ewing sarcoma (ES), where long term survival rates are still below
      20%. Despite significant progress in our understanding of ES biology, clinical
      translation of promising laboratory results has not yet taken place due to
      fragmentation of research and lack of an institutionalized discussion forum. To
      fill this gap, ENCCA assembled 30 European expert scientists and five North
      American opinion leaders in December 2011 to exchange thoughts and discuss the
      state of the art in ES research and latest results from the bench, and to propose
      biological studies and novel promising therapeutics for the upcoming European
      EWING2008 and EWING2012 clinical trials.

PMID- 22662319
TI  - Deregulation of ion channel and transporter encoding genes in pediatric gliomas.
AB  - Brain tumors, including the majority gliomas, are the leading cause of cancer
      related death in children. World Health Organization has divided pediatric brain
      tumors into different grades and, based upon cDNA microarray data identifying
      gene expression profiles (GEPs), it has become evident in the last decade that
      the various grades involve different types of genetic alterations. However, it is
      not known whether ion channel and transporter genes, intimately involved in brain
      functioning, are associated with such GEPs. We determined the GEPs in an
      available cohort of 10 pediatric brain tumors initially by comparing the data
      obtained from four primary tumor samples and corresponding short-term cultures.
      The correspondence between the two types of samples was statistically
      significant. We then performed bioinformatic analyses on those samples (a total
      of nine) which corresponded to tumors of glial origin, either tissues or cell
      cultures, depending on the best "RNA integrity number." We used R software to
      evaluate the genes which were differentially expressed (DE) in gliomas compared
      with normal brain. Applying a p-value below 0.01 and fold change >=4, led to
      identification of 2284 DE genes. Through a Functional Annotation Analysis (FAA)
      using the NIH-DAVID software, the DE genes turned out to be associated mainly
      with: immune/inflammatory response, cell proliferation and survival, cell
      adhesion and motility, neuronal phenotype, and ion transport. We have shown that
      GEPs of pediatric brain tumors can be studied using either primary tumor samples
      or short-term cultures with similar results. From FAA, we concluded that, among
      DE genes, pediatric gliomas show a strong deregulation of genes related to ion
      channels and transporters.

PMID- 22662321
TI  - Permeation profiles of potential urine-borne biomarkers of human presence over
      brick and concrete.
AB  - Headspace solid phase micro-extraction gas chromatography-mass spectrometry (SPME
      GC-MS) analysis was performed over an in-house made filling chamber loaded with
      brick or concrete, mimicking a potential entrapment scene of building collapse
      following natural or man-made disasters. Permeation profiles of 22 volatile
      species, released by human urine samples, were quantitatively monitored over the
      selected debris materials for a time period of 24 hours (LODs ranged from 0.05
      0.8 ppb, R(2) varied from 0.991-0.999 and RSDs 3-9%). Ketones were the most
      abundant constituents of urine vapor with eleven representatives followed by five
      aldehydes, two furans, two sulphur-containing compounds, one nitrile and one
      heterocyclic compound. The majority of the detected compounds were found below 10
      ppb, with the exception of some ketones including acetone, 2-butanone and 2
      pentanone. The influence of debris materials on the permeation profiles of
      analytes under study depended on their fundamental physicochemical properties.
      Less volatile and more soluble compounds in urine (ketones and aldehydes) were
      found to be present for longer time periods in the surroundings of the urine
      samples than the more volatile and poorly soluble ones (furans, sulphur
      containing compounds). More specifically, ketones exhibited longer residence
      times in the filling chamber and strongly interacted with the debris materials as
      their molecular masses were increased; their profiles were found to be
      significantly modified in the presence of concrete. In general, concrete
      demonstrated a stronger interaction with urine species than brick, affecting the
      observed concentrations and residence times of released volatiles in the chamber.

PMID- 22662322
TI  - Ultrasensitive electrochemiluminescence detection of DNA based on nanoporous gold
      electrode and PdCu@carbon nanocrystal composites as labels.
AB  - A sensitive electrochemiluminescence (ECL) DNA biosensor based on nanoporous gold
      (NPG) electrode and PdCu@carbon nanocrystals (CNCs) composites is developed. The
      CNCs were obtained simply by electrooxidation with abundant carboxyl groups at
      their surfaces. The NPG can be easily prepared by a selective dissolution of
      silver from silver-gold alloy in nitric acid, which has free-standing noble metal
      membranes with controllable three-dimensional (3D) porosity. The PdCu bimetallic
      nanocomposites with hierarchically hollow structures were fabricated through a
      simple replacement reaction using dealloyed nanoporous copper (NPC) as both a
      template and reducing agent. Structure characterization was obtained by means of
      transmission electron microscope (TEM) and scanning electron microscope (SEM)
      images. The PdCu@CNCs composites exhibit 6 times higher ECL intensity than the
      pure CNC-labeled reporter DNA. Taking advantage of dual-amplification effects of
      the developed probe, a limit of detection as low as 18 aM can be achieved and the
      assay exhibits excellent selectivity for single-mismatched DNA detection even in
      human serum. The proposed ECL based method should have wide applications in
      diagnosis of genetic diseases due to its simplicity, low cost, and high
      sensitivity at extremely low concentrations.

PMID- 22662323
TI  - A colorimetric sensor based on catechol-terminated mixed self-assembled
      monolayers modified gold nanoparticles for ultrasensitive detections of copper
      ions.
AB  - A colorimetric sensor for Cu(II) ions has been developed based on mixed self
      assembled monolayers (SAMs) modified gold nanoparticles (AuNPs). The AuNPs were
      modified with mixed SAMs consisting of mercaptosuccinic acid and the product of
      electrochemically triggered Michael addition reaction of 4-thiouracil and
      catechol. In the presence of Cu(II) ions, the coordination of Cu(2+) to catechol
      terminated AuNPs leads to aggregation-induced changes of surface plasmon
      resonance. The cost-effective chemical sensor allows rapid, sensitive and
      selective detection of Cu(2+) ions, indicating its potential application in
      environmental field.

PMID- 22662325
TI  - Cyclohexane selective oxidation over metal-organic frameworks of MIL-101 family:
      superior catalytic activity and selectivity.
AB  - Mesoporous metal-organic frameworks Cr- and Fe-MIL-101 are highly efficient, true
      heterogeneous and recyclable catalysts for solvent-free selective oxidation of
      cyclohexane with molecular oxygen and/or tert-butyl hydroperoxide under mild
      conditions.

PMID- 22662324
TI  - Non-asymmetric organocatalysis.
AB  - Asymmetric organocatalysis is now an established methodology for the preparation
      of chiral compounds. However, these are not the only valuable molecules which can
      be conveniently obtained. Organocatalytic reactions affording achiral compounds
      are gaining momentum, opening unexplored pathways in the synthesis of densely
      functionalized aromatic moieties, olefins and useful molecules such as natural
      substances.

PMID- 22662326
TI  - Multichannel HSO4- recognition promoted by a bound cation within a ferrocene
      based ion pair receptor.
AB  - A ferrocene-based ion pair receptor is shown only to recognise HSO(4)(-) anions
      in the presence of a cobound Pb(2+) or Zn(2+) cation guest species through a
      perturbation of the redox potential of the ferrocene unit and a remarkable
      enhancement of the fluorescence.

PMID- 22662327
TI  - Catalytic asymmetric Mannich-type reactions of alpha-cyano alpha-sulfonyl
      carbanions.
AB  - An efficient asymmetric Mannich-type reaction of alpha-cyano alpha-sulfonyl
      carbanions has been achieved by exploiting the structural modularity and anion
      recognition ability of chiral 1,2,3-triazolium ions. This protocol has proven to
      be applicable to a variety of N-Boc imines and cyanosulfones, affording beta
      amino alpha-cyanosulfones in excellent yields with high stereoselectivities.

PMID- 22662328
TI  - Intermediates in the Rh-catalysed dehydrocoupling of phosphine-borane.
AB  - Active species, product distributions and a suggested catalytic cycle are
      reported for the dehydrocoupling of the phosphine-borane H(3)B.P(t)Bu(2)H to give
      HP(t)Bu(2)BH(2)P(t)Bu(2)BH(3) using the [Rh(COD)(2)][BAr(F)(4)] pre-catalyst.

PMID- 22662329
TI  - Blue emitting gold nanoclusters templated by poly-cytosine DNA at low pH and poly
      adenine DNA at neutral pH.
AB  - Blue fluorescent gold nanoclusters were prepared in the presence of poly-cytosine
      DNAs at low pH and poly-adenine at neutral pH using citrate as the reducing
      agent; various buffer conditions affecting the synthesis have been explored.

PMID- 22662330
TI  - Reversible structural switch in the nano-cavity of crystalline metallo
      macrocycles with smooth ligand exchange by non-coordinating guest stimuli.
AB  - A tetranuclear Ni(II)-macrocycle consisting of beta-dipeptides demonstrates
      effects of water vapor on the structural switching of the nano-cavity by ligand
      exchange in the single-crystal state. The content of non-coordinating water
      molecules regulates the opening and closing of the cavity through cooperation of
      smooth ligand exchange and internal hydrogen-bond switching.

PMID- 22662331
TI  - Emergency department computed tomography use under fire: emergency physicians
      defend imaging practices.

PMID- 22662332
TI  - ACGME tightens postgraduate training entry requirements: doctors of osteopathic
      medicine, international medical graduates most affected.

PMID- 22662333
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention. Carbapenem-resistant Klebsiella pneumoniae associated with a long
      term-care facility-West Virginia, 2009-2011.

PMID- 22662334
TI  - Thinking out of the box.

PMID- 22662335
TI  - Renato Dulbecco:a Renaissance scientist.

PMID- 22662336
TI  - [Occupational dermatology: congratulations to an early victory].

PMID- 22662337
TI  - Cornell University and modern biology in China.

PMID- 22662338
TI  - Malyugin ring for pediatric cataract surgery.

PMID- 22662339
TI  - Nodular fasciitis of the breast.
AB  - Nodular fasciitis of the breast is a rare, benign, soft-tissue tumor that can
      clinically and radiologically mimic invasive ductal carcinoma. A 25-year-old
      woman presented with a palpable lesion in the lower inner aspect of the left
      breast. Radiologically, breast carcinoma could not be excluded. On examination of
      the core needle biopsy, the tumor was characterized histologically as a spindle
      cell tumor. Excisional biopsy was performed. The tumor was diagnosed as nodular
      fasciitis of the breast. The imaging and histological findings of this case are
      presented.

PMID- 22662340
TI  - Recombinant VirB5 protein as a potential serological marker for the diagnosis of
      bovine brucellosis.
AB  - The molecular tag vaccine against Brucella abortus and serological testing are
      the main methods of prevention of brucellosis used currently. They can
      discriminate vaccinated animals and humans from those naturally infected. In this
      study, we constructed a gene deletion mutant strain, B. abortus S19 virB5 with a
      molecular tag. Recombinant VirB5 was expressed and purified for evaluation as a
      diagnostic reagent for bovine brucellosis. In total, 400 sera samples were tested
      using a VirB5 antigen-based enzyme-linked immunosorbent assay (ELISA) and the
      results were compared with those of the standard tube agglutination test (SAT).
      This showed that the sensitivity was 88.2%, specificity was 97.8% and accuracy
      was 94.8%. Recombinant VirB5 could also be used to discriminate B. abortus
      infected mice from mice infected with the B. abortus S19 virB5 mutant strain. It
      was concluded that recombinant VirB5 could be used as a potential antigen and
      serological marker for the diagnosis of bovine brucellosis.

PMID- 22662342
TI  - Retraction. Placental alpha-microglobulin-1 rapid immunoassay for detection of
      premature rupture of membranes.

PMID- 22662343
TI  - Are your people too afraid to report errors?

PMID- 22662341
TI  - Tritrichomonas--systematics of an enigmatic genus.
AB  - Tritrichomonas spp. are parasitic protozoans that proliferate on mucus membranes
      of the urogenital, gastro-intestinal or nasal tract. For instance, Tritrichomonas
      foetus is an important cause of reproductive failure in cattle. Some years ago,
      T. foetus was also identified as a causative agent of diarrhoea in cats. Previous
      studies on the morphological, physiological and molecular levels have raised
      doubts as to the phylogenetic relationship among some Tritrichomonas species,
      particularly in relation to T. foetus, Tritrichomonas suis, and Tritrichomonas
      mobilensis. With the advent of molecular genetic tools, it has become clear that
      these three tritrichomonad species are closely related or may even represent the
      same species. Indeed, since recently, T. suis and T. foetus are generally
      considered as one species, with T. mobilensis being a closely related sister
      taxon. To date, molecular studies have not yet been able to resolve the taxonomic
      (specific) status of T. foetus from cattle and cats. In the future, novel genomic
      approaches, particularly those involving next generation sequencing are poised to
      resolve the taxonomy of Tritrichomonas spp. Here, we review the literature on the
      current state of knowledge of the taxonomy of T. foetus, T. suis, and T.
      mobilensis with special reference to the relationship between T. foetus from
      cattle and cats.

PMID- 22662344
TI  - Letting it all hang out does not seem to matter.

PMID- 22662345
TI  - Improving emergency department wait times.

PMID- 22662346
TI  - Why do it if you can't measure it?

PMID- 22662347
TI  - Errata.
AB  - [This corrects the article on p. 1161 in vol. 34, PMID: 21886353.].

PMID- 22662348
TI  - The tragedy of the commodity and the farce of AquAdvantage Salmon.
AB  - The US Food and Drug Administration is expected to approve AquAdvantage Salmon as
      the first genetically modified animal for human consumption. The genetic
      modifications allow the proprietary fish to grow at a rate twice as fast as a
      wild salmon, leading to greater 'efficiency' in terms of reduced costs and
      reduced time to market. This article provides an analysis of the ways in which
      AquAdvantage Salmon exemplifies capitalist market forces controlling and guiding
      the terms of salmon recovery and conservation. The authors trace historical
      developments within the salmon industry to demonstrate how capitalist commodity
      production has impacted fishing communities. They reject the oft-cited 'tragedy
      of the commons' hypothesis offered to explain fisheries crises. In its place,
      they offer the conceptual framework of the 'tragedy of the commodity' to explore
      how capitalist market forces and complicit state regulations amplify rather than
      resolve global environmental problems.

PMID- 22662349
TI  - Geoengineering: re-making climate for profit or humanitarian intervention?
AB  - Climate engineering, or geoengineering, refers to large-scale climate
      interventions to lower the earth's temperature, either by blocking incoming
      sunlight or removing carbon dioxide from the biosphere. Regarded as 'technofixes'
      by critics, these strategies have evoked concern that they would extend the shelf
      life of fossil-fuel driven socio-ecological systems for far longer than they
      otherwise would, or should, endure. A critical reading views geoengineering as a
      class project that is designed to keep the climate system stable enough for
      existing production systems to continue operating. This article first examines
      these concerns, and then goes on to envision a regime driven by humanitarian
      agendas and concern for vulnerable populations, implemented through international
      development and aid institutions. The motivations of those who fund research and
      implement geoengineering techniques are important, as the rationale for
      developing geoengineering strategies will determine which techniques are pursued,
      and hence which ecologies are produced. The logic that shapes the geoengineering
      research process could potentially influence social ecologies centuries from now.

PMID- 22662350
TI  - The proliferation of brands: the case of food in Belgium, 1890-1940.

PMID- 22662352
TI  - Rituals of creativity: tradition, modernity, and the "acoustic unconscious" in a
      U.S. collegiate jazz music program.
AB  - In this article, I seek to complicate the distinction between imitation and
      creativity, which has played a dominant role in the modern imaginary and
      anthropological theory. I focus on a U.S. collegiate jazz music program, in which
      jazz educators use advanced sound technologies to reestablish immersive
      interaction with the sounds of past jazz masters against the backdrop of the
      disappearance of performance venues for jazz. I analyze a key pedagogical
      practice in the course of which students produce precise replications of the
      recorded improvisations of past jazz masters and then play them in synchrony with
      the recordings. Through such synchronous iconization, students inhabit and
      reenact the creativity epitomized by these recordings. I argue that such a
      practice, which I call a "ritual of creativity," suggests a coconstitutive
      relationship between imitation and creativity, which has intensified under
      modernity because of the availability of new technologies of digital
      reproduction.

PMID- 22662351
TI  - Instant noodles as an antifriction device: making the BOP with PPP in PNG.
AB  - Focusing primarily, but not exclusively, on urban and periurban Papua New Guinea
      (PNG), we discuss the significance of instant ramen noodles to those now known as
      the "bottom of the pyramid" (BOP). Although instant noodles are remarkable in
      that they are eaten by virtually everyone in the world, albeit in different
      amounts and for different reasons, they are marketed in PNG specifically as a
      "popularly positioned product" (PPP) for the BOP. Cheap, convenient, tasty,
      filling, and shelf stable, they are a modern addition to Sidney Mintz's classic
      "proletarian hunger killers" of sugar, tea, and coffee. But, we argue, instant
      noodles have a distinctive contemporary role: they do more than sustain the poor;
      they transform them into the aspiring consumers of the BOP. As such, instant
      noodles can be viewed as an antifriction device, greasing the skids of capitalism
      as it extends its reach.

PMID- 22662353
TI  - Cattle cults of the Arabian Neolithic and early territorial societies.
AB  - At the cusp of food production, Near Eastern societies adopted new territorial
      practices, including archaeologically visible sedentism and nonsedentary social
      defenses more challenging to identify archaeologically. New archaeological and
      paleoenvironmental evidence for Arabia's earliest-known sacrifices points to
      territorial maintenance in arid highland southern Yemen. Here sedentism was not
      an option prior to agriculture. Seasonally mobile pastoralists developed
      alternate practices to reify cohesive identities, maintain alliances, and defend
      territories. Archaeological and paleoenvironmental evidence implies cattle
      sacrifices were commemorated with a ring of more than 42 cattle skulls and a
      stone platform buried by 6,400-year-old floodplain sediments. Associated with
      numerous hearths, these cattle rites suggest feasting by a large gathering, with
      important sociopolitical ramifications for territories. A GIS analysis of the
      early Holocene landscape indicates constrained pasturage supporting small
      resident human populations. Cattle sacrifice in southern Arabia suggests a model
      of mid-Holocene Neolithic territorial pastoralism under environmental and
      cultural conditions that made sedentism unsusta

PMID- 22662354
TI  - Architecture as animate landscape: circular shrines in the ancient Maya lowlands.
AB  - In this study, I develop a theory of landscape archaeology that incorporates the
      concept of "animism" as a cognitive approach. Current trends in anthropology are
      placing greater emphasis on indigenous perspectives, and in recent decades
      animism has seen a resurgence in anthropological theory. As a means of relating
      in (not to) one's world, animism is a mode of thought that has direct bearing on
      landscape archaeology. Yet, Americanist archaeologists have been slow to
      incorporate this concept as a component of landscape theory. I consider animism
      and Nurit Bird-David's (1999) theory of "relatedness" and how such perspectives
      might be expressed archaeologically in Mesoamerica. I examine the distribution of
      marine shells and cave formations that appear incorporated as architectural
      elements on ancient Maya circular shrine architecture. More than just "symbols"
      of sacred geography, I suggest these materials represent living entities that
      animate shrines through their ongoing relationships with human and other-than
      human agents in the world.

PMID- 22662355
TI  - Principle or pathology? Adjudicating the right to conscience in the Israeli
      military.
AB  - The Israeli military's Conscience Committee evaluates and exempts pacifists from
      obligatory military service, based explicitly on concern for liberal tolerance.
      However, I found that liberal pacifist applicants' principled objections to
      violence challenged the state, and as such, applicants who articulated their
      refusal in such terms are rejected by the military review board. By contrast,
      pacifist conscientious objection based in embodied visceral revulsion to violence
      did not challenge the state and moral order, and such cases were granted
      exemption. Objections based in understanding pacifism as a physical incapacity
      depoliticizes it by making it incommensurable with public moral debate concerning
      military service. The pathologization of pacifism demonstrates a contradiction
      between liberalism's ideology and its practices, revealing that the limits of
      liberalism are not only exterior, in nonliberal alterity, but also on
      liberalism's own interior frontiers.

PMID- 22662356
TI  - When "humanitarianism" becomes "development": the politics of international aid
      in Syria's Palestinian refugee camps.
AB  - In recent years, the United Nations Relief and Works Agency for Palestine
      Refugees in the Near East (UNRWA) has attempted to go beyond its role as a
      provider of relief and basic services in Palestinian refugee camps and emphasize
      its role as a development agency. In this article, I focus on the Neirab
      Rehabilitation Project, an UNRWA-sponsored development project taking place in
      the Palestinian refugee camps of Ein el Tal and Neirab in northern Syria. I argue
      that UNRWA's role as a relief-centered humanitarian organization highlights the
      everyday suffering of Palestinian refugees, suffering that has become embedded in
      refugees' political claims. I show that UNRWA's emphasis on "development" in the
      refugee camps is forcing Palestinian refugees in Ein el Tal and Neirab to
      reassess the political narrative through which they have understood their
      relationship with UNRWA.

PMID- 22662357
TI  - Moral maps and medical imaginaries: clinical tourism at Malawi's College of
      Medicine.
AB  - At an understaffed and underresourced urban African training hospital, Malawian
      medical students learn to be doctors while foreign medical students, visiting
      Malawi as clinical tourists on short-term electives, learn about "global health."
      Scientific ideas circulate fast there; clinical tourists circulate readily from
      outside to Malawi but not the reverse; medical technologies circulate slowly,
      erratically, and sometimes not at all. Medicine's uneven globalization is on full
      display. I extend scholarship on moral imaginations and medical imaginaries to
      propose that students map these wards variously as places in which-or from which
      they seek a better medicine. Clinical tourists, enacting their own moral maps,
      also become representatives of medicine "out there": points on the maps of
      others. Ethnographic data show that for Malawians, clinical tourists are
      colleagues, foils against whom they construct ideas about a superior and
      distinctly Malawian medicine and visions of possible alternative futures for
      themselves.

PMID- 22662358
TI  - A biocultural approach to breastfeeding interactions in Central Africa.
AB  - Anthropologists have long recognized that breastfeeding involves much more than
      feeding; it entails intimate social interactions between infants or children and
      their mothers. However, breastfeeding has predominantly been studied with respect
      to structural features (frequency, timing) as well as nutritional and health
      aspects of infant feeding. Thus, in this study we complement previous
      anthropological studies by examining social interactions that occur during
      breastfeeding among the Aka and Bofi foragers and Ngandu and Bofi farmers at
      various ages (three to four months, nine to ten months, toddlers). Further, we
      use an integrated biocultural perspective to explore how patterns of
      breastfeeding and social interactions can be shaped by economic constraints,
      cultural values, and children's development. Overall, our findings illustrate how
      biological and cultural factors interact and provide useful explanations of
      variations in breastfeeding structure and social interactions more so than either
      perspective alone.

PMID- 22662359
TI  - [Melanoma and non-melanoma skin cancers].

PMID- 22662360
TI  - [Guideline for the management of melanoma: outline and point of revision-novel
      chemotherapy-].

PMID- 22662361
TI  - [Cutaneous squamous cell carcinoma: current topics].

PMID- 22662362
TI  - [Guideline for the management of basal cell carcinoma: outline and point of
      revision].

PMID- 22662363
TI  - [Guideline for the management of skin lymphoma: outline and point of revision].

PMID- 22662364
TI  - Green "Angels in America": aesthetics of equity.

PMID- 22662366
TI  - Locavores, feminism, and the question of meat.

PMID- 22662365
TI  - Marginal voices in "wild" America: race, ethnicity, gender, and "nature" in "The
      National Parks".

PMID- 22662367
TI  - Dead bodies that matter: toward a new ecology of human death in American culture.

PMID- 22662368
TI  - High-fidelity birth simulators in American culture: an ecofeminist analysis.

PMID- 22662369
TI  - At the heart of nursing.

PMID- 22662370
TI  - The use of phenomenology in nursing research.

PMID- 22662371
TI  - An introduction to Moustakas's heuristic method.
AB  - AIM: This paper is intended to introduce Moustakas's heuristic method to a wider
      nursing research audience. It is aimed at identifying the main principles that
      underpin this approach, and outlining the processes and structure that this form
      of inquiry might take. BACKGROUND: Heurism is a generic term that encapsulates a
      way of thinking and exploring that is shared by such diverse disciplines as
      computer programming, mathematics and philosophy. All these disciplines at some
      point require an understanding of the process that comprises the experience of
      discovery that pre-empts the formulation of a hypothesis. REVIEW METHODS: The
      heuristic method is critically reviewed and its strengths are identified. The
      discourse offered by post-modernism, which challenges some of the method's main
      principles, is explored and potential solutions offered. DISCUSSION: This paper
      highlights how research questions that are heuristic in origin can create
      conditions that offer the possibility for change in the researcher. It explores
      how the internal change that occurs in the researcher can be a catalyst for
      deeper appreciation of the question under investigation and how this personal
      transformation can be relevant for practice and research. CONCLUSION: Nursing
      practice and research are ideally placed to engage with questions that emerge
      heuristically from our experience. IMPLICATIONS: for research/practice
      Moustakas's method gives practitioners and researchers the opportunity to explore
      internal and personal questions. It suggests that the personal nature of these
      questions can contribute to the contexts and environments in which care and
      research take place.

PMID- 22662372
TI  - The utility of human sciences in nursing inquiry.
AB  - AIM: This paper targets novice nurse researchers to highlight how the
      perspectives of human sciences are useful in understanding people's experiences.
      BACKGROUND: There is a need to address the utility of human sciences or the
      humanistic philosophy that values the understanding of subjective experiences in
      nursing, given that the mainstream development of nursing knowledge is still
      influenced by the positivist and post-positivist research paradigms. DATA
      SOURCES: Discussion papers on Heideggerian hermeneutic phenomenology, human
      sciences, and qualitative research were accessed through the databases Cinahl and
      Medline over the past 30 years. Seminal works on phenomenology were addressed in
      this paper. DISCUSSION: Using Heideggerian hermeneutic phenomenology as a
      commonly referenced human philosophy and methodology, this paper discusses how
      Heidegger's (1962) perspective may be used in nursing practice and research. Van
      Manen's (1990) descriptions of phenomenological science are discussed to address
      the perspective's value in nursing inquiry and to reveal the biases associated
      with this humanistic approach. CONCLUSION: The limitations of human sciences
      should not deter nurse researchers from using this type of nursing inquiry as it
      can provide an important framework in nursing research, practice and knowledge
      development. IMPLICATIONS FOR RESEARCH/PRACTICE: The author's perspective as a
      graduate student highlights the importance of human sciences in exploring the
      experiences of people vital in the delivery of nursing practice. However,
      researchers wishing to undertake humanistic inquiry should learn the
      philosophical and methodological underpinnings of their chosen humanistic
      approach.

PMID- 22662373
TI  - Rigour in phenomenological research: reflections of a novice nurse researcher.
AB  - AIM: This paper is intended to explore conflicts and doubts that novice
      researchers face when using phenomenological research methods, especially with
      regard to methodological rigour. BACKGROUND: There is an increasing interest in
      different qualitative approaches. The best way to evaluate the quality of
      qualitative studies has been debated intensively. The great theoretical and
      methodological diversity of qualitative approaches suggests that a single set of
      criteria may not be appropriate for all types of research. REVIEW METHODS: This
      is a methodological paper that discusses a personal experience of addressing
      rigour in a phenomenological study, supported by literature on the topic.
      DISCUSSION: Generic qualitative criteria may not be the most adequate to ensure
      rigour in phenomenological research. The different poles of discussion about the
      best way to ensure validity of phenomenological research puzzle novice nurse
      researchers. CONCLUSION: Focusing on integrative validity that addresses
      experiential and methodological concerns ensures that researchers will respect
      the philosophical assumptions underlying a method and allows them to recognise
      study soundness in the findings and the research process. IMPLICATIONS FOR
      RESEARCH/PRACTICE: Phenomenological research must demonstrate methodological
      congruence and provide meaningful results about lived experiences in a balanced
      way. Novice researchers need support to understand the articulation between
      philosophical and methodological foundations that guide the methods they use.

PMID- 22662374
TI  - The use of visual methodology in nursing.
AB  - AIM: To explore the use of visual methodology in nursing. BACKGROUND: Interest in
      the use of visual methodologies is increasing and its use can be adopted in
      healthcare research. DATA SOURCES: Commentary on a study that used drawings to
      explore stress-busting behaviours in nursing students. REVIEW METHODS: Drawing
      from the literature and practical experience, the paper explores the traditions
      of visual research and aspects such as terminology, analysis, ethical issues, the
      advantages and disadvantages of the methodology, and the implications of using
      visual methodology. DISCUSSION: Visual methodology revealed information that
      perhaps would not be elicited by interviews or questionnaires. Dialogue should
      take place, along with images, to ensure correct interpretation. CONCLUSION:
      Digital technology enables the use of visual methodology, which is new in health
      care and can offer many opportunities to researchers. IMPLICATIONS FOR
      RESEARCH/PRACTICE: Visual research methodologies have the potential to expand in
      nursing research because of their range of data collection and analytical
      frameworks and because of the possibility of working with the participant.

PMID- 22662375
TI  - Journaling: identification of challenges and reflection on strategies.
AB  - AIMS: To identify the challenges associated with using journaling as a method of
      data collection and to offer strategies for effectively managing those
      challenges. BACKGROUND: While journaling can be used for a variety of reasons, in
      the context of this paper, journaling refers to the process of participants
      sharing thoughts, ideas, feelings and experiences through writing and/or other
      media. Journaling is used in phenomenological research studies to record
      participant experiences in their natural contexts. DATA SOURCES: The findings are
      based on the experiences of the researchers during a qualitative study that
      explored the experiences of lesbian mothers and used journaling as one method of
      data collection. REVIEW METHODS: This is a methodological paper. DISCUSSION:
      Three main challenges affect journaling as a method of data collection: poor
      participation, feeling exposed and staying on track. Six strategies to promote
      participation in journaling are: coaching participants, limiting the journaling
      period, providing follow-up contact, promoting comfort, ensuring safety and
      providing clear content expectations. Each strategy is discussed and methods of
      implementing the strategies are offered. CONCLUSION: Journaling as a method of
      data collection has long been accepted as a valid method of accessing rich
      qualitative data. By acknowledging the common challenges associated with the
      process of journaling that are experienced by the participants, researchers
      employing this data collection method can promote constructive and valuable
      participation. IMPLICATIONS FOR FUTURE RESEARCH: Further research examining
      participants' experiences of journaling as a method of qualitative data
      collection would be useful in determining challenges, barriers and benefits of
      the method.

PMID- 22662376
TI  - Assessing children's and parents' opinions on salivary sampling for therapeutic
      drug monitoring.
AB  - AIM: This paper describes preliminary development and pilot testing of a
      questionnaire to assess opinions on saliva sampling for therapeutic drug
      monitoring (TDM) in paediatric patients. BACKGROUND: Less distressing
      alternatives are needed for sampling body fluids from children and young people
      for TDM to obtain results that are as accurate as those attained from blood
      samples. DATA SOURCES: Two versions of a salivary sampling questionnaire were
      developed, one for young children and one for older children and young people and
      administered to two cohorts of 15 children and young people aged from eight to 19
      years, and their parents. Questionnaire refinement based on feedback from the
      first was undertaken before administration tothe second. Data were analysed
      thematically. DISCUSSION: Where saliva sampling is a viable alternative to blood
      sampling, it should be offered in-clinic as well as at home to provide
      opportunities for direct communication with clinicians if that is the preferred
      option for children and young people. CONCLUSION: The questionnaire has potential
      value for assessing preferences in clinical scenarios involving where saliva
      sampling may be indicated. IMPLICATIONS FOR FUTURE RESEARCH: Ongoing research is
      needed to inform item development and refinement, and to investigate
      questionnaire validity and psychometric performance.

PMID- 22662377
TI  - Revisiting Mandell's 'least adult' role and engaging with children's voices in
      research.
AB  - AIM: This paper is intended to re-examine Mandell's classic work on the 'least
      adult' role and to show that the principles that underpin Mandell's work are
      useful if combined with a reflexive approach to working with children.
      BACKGROUND: Researching with children (Christensen and James 2008) using
      participatory methods has become an accepted research methodology. However,
      research reports that claim to represent the views of children rarely detail how
      the research relationships between children and adults are managed. DATA SOURCES:
      Mandell's work on the least-adult role in studying children and other
      contemporary texts on researching with children. REVIEW METHODS: Re-examination
      of the principles of Mandell's approach to conducting participatory research with
      children using other contemporary texts on researching with children and
      participatory research with children. DISCUSSION: The work of other researchers
      with children would appear to endorse the principles that Mandell suggests as
      useful when engaging children in research: to minimise the social difference
      between adult and child, to value the child's social world, and to join with
      children in activities such as play or arts-based participatory methods. The
      issue of trust seems to extend beyond the relationship between researcher and
      participant to include building trust with other adults in whom the child has
      confidence. In applying these principles and building trust, researchers need to
      be reflexive about their understanding of children and childhood. CONCLUSION: To
      evaluate research with children, research reports need to include discussions of
      how the researchers addressed Mandell's principles and built trust. Data given by
      children are influenced by how social differences are minimised, the perceived
      value the researcher places on children's social worlds and how children are
      engaged in the research process. IMPLICATION FOR PRACTICE/RESEARCH: Further
      research is required to understand how various approaches to minimising social
      difference, valuing children's social worlds, joining children in activities and
      building trust can influence children's participation and the data they give.

PMID- 22662378
TI  - Let patients drive the research.

PMID- 22662379
TI  - Oral HPV: the need for patient education.

PMID- 22662380
TI  - Legal concerns with dental practice websites.

PMID- 22662381
TI  - Substance abuse questions and answers.

PMID- 22662382
TI  - Keeping a former owner's name on the practice: is it ethical?

PMID- 22662383
TI  - New plan now available helps insure you against critical illness.

PMID- 22662384
TI  - Facts about dental plans and focused review.

PMID- 22662385
TI  - Determining the appropriate fees for your office.

PMID- 22662386
TI  - When should you worry about 'senior moments'?

PMID- 22662387
TI  - What you need to know about the MDA's public education campaign.

PMID- 22662388
TI  - The Calhoun County Dentists' Partnership: A hands-up, not a hand-out.

PMID- 22662389
TI  - A current perspective on Sjogren's syndrome.

PMID- 22662390
TI  - The smoking patterns of women in their forties: their relationship to later
      osteoporosis.
AB  - Osteoporosis is prevalent among women 50 years of age and older and accounts for
      numerous fractures and the related deaths of many sufferers. In this study, 22.4%
      of the women reported having osteoporosis. Smoking contributes substantially to
      osteoporotic fractures. This study assessed how different trajectories of women's
      smoking, covering the ages 40 to 48 years, relate to osteoporosis at age 65.
      Trajectory analysis of tobacco use data reveals smoking patterns which may have
      differing relationships to osteoporosis. Logistic regression analyses revealed
      the varying relationships of different smoking patterns to osteoporosis. As
      hypothesized, the chronic/heavy smokers were significantly more likely than the
      non-smokers to report having osteoporosis. Quitters and moderate smokers did not
      differ significantly from non-smokers on the osteoporosis measure. Chronic/heavy
      smokers should not be the only focus of public health efforts to reduce smoking
      and the associated risks of osteoporosis. The findings also highlight the
      efficacy of women smokers quitting in their 40s in order to reduce their
      likelihood of contracting osteoporosis.

PMID- 22662391
TI  - Characteristics of schools in which fatal shootings occur.
AB  - School-based violence, and fatal school shootings in particular, have gained
      increased attention in the media and psychological literature. Most reports have
      focused on the characteristics of perpetrators, but there is a growing awareness
      that school-related factors may also influence the occurrence of fatal school
      shootings. The current study examined several key characteristics of all schools
      where random (38) and targeted (96) fatal shootings occurred in the United States
      between 1966 and 2009. These were compared with a group (138) of schools randomly
      selected to represent the population of all schools in the United States. The
      size of a school's enrollment, urban or suburban locale, public funding, and
      predominantly non-white enrollment were positively associated with fatal
      shootings. Universities and colleges were disproportionately associated with
      random shootings and high schools with targeted ones. It was proposed that
      characteristics of schools that allow feelings of anonymity or alienation among
      students may help create environmental conditions associated with fatal school
      shootings. Implications for future research and interventions are considered.

PMID- 22662392
TI  - Reliability of the Ego-Grasping Scale.
AB  - Research using Knoblauch and Falconer's Ego-Grasping Scale is reviewed. Using a
      sample of 695 undergraduate students, the scale had moderate reliability
      (Cronbach alpha, odd-even numbered items, and test-retest), but a principal
      components analysis with a varimax rotation identified five components,
      indicating heterogeneity in the content of the items. Lower Ego-Grasping scores
      appear to be associated with better psychological health. The scale has been
      translated and used with Korean, Kuwaiti, and Turkish students, indicating that
      the scale can be useful in cross-cultural studies.

PMID- 22662393
TI  - A comparison of paper-and-pencil and computerized forms of Line Orientation and
      Enhanced Cued Recall Tests.
AB  - The purpose of this study was to assess whether a computerized battery of
      neuropsychological tests could produce similar results as the conventional forms.
      Comparisons on 77 volunteer undergraduates were carried out with two
      neuropsychological tests: Line Orientation Test and Enhanced Cued Recall Test.
      Firstly, students were assigned randomly across the test medium (paper-and-pencil
      versus computerized). Secondly, the groups were given the same test in the other
      medium after a 30-day interval between tests. Results showed that the Enhanced
      Cued Recall Test-Computer-based did not correlate with the Enhanced Cued Recall
      Test-Paper-and-pencil results. Line Orientation Test-Computer-based scores, on
      the other hand, did correlate significantly with the Line Orientation Test-Paper
      and-pencil version. In both tests, scores were higher on paper-and-pencil tests
      compared to computer-based tests. Total score difference between modalities was
      statistically significant for both Enhanced Cued Recall Tests and for the Line
      Orientation Test. In both computer-based tests, it took less time for
      participants to complete the tests.

PMID- 22662394
TI  - Change in self-concept differentiation after psychotherapy and its relation to
      psychological maladjustment.
AB  - The research was carried out with a group of 105 psychotherapy participants,
      diagnosed with neurosis or personality disorders, and 36 controls. Analysis
      supported the hypotheses that self-concept differentiation (SCD) decreases after
      psychotherapeutic interventions and that the reduction in SCD is positively
      correlated with an improvement in neurotic symptoms and neurotic personality
      traits.

PMID- 22662395
TI  - Self-estimates of intelligence: interaction effects of the comparison to a
      specific reference group and neuroticism.
AB  - An experiment that investigated the interaction effect of Neuroticism and the
      comparison to different reference groups on self-estimates of intelligence is
      reported. University students (100 men, 15 women) were randomly assigned to two
      experimental groups and asked to rate their own intelligence on a one-item
      measure, in IQ points, having been provided with reference values for either the
      general population or a student sample. Analysis of data confirmed that the
      accuracy of self-estimates of intelligence was influenced by the variation of the
      instruction. Participants provided more accurate estimations when confronted with
      comparison information about fellow students than about the general population.
      Persons scoring high on Neuroticism estimated their intelligence lower, but only
      when their estimation was based on a general reference group. Theoretical and
      practical implications were discussed.

PMID- 22662396
TI  - Exploring the relationships between free-time management and boredom in leisure.
AB  - The purpose of the study was to examine the relations of five dimensions of free
      time management (including goal setting and evaluating, technique, values,
      immediate response, and scheduling) with leisure boredom, and whether these
      factors could predict leisure boredom. A total of 500 undergraduates from a
      university in southern Taiwan were surveyed with 403 usable questionnaires was
      returned. Pearson correlation analysis revealed that five dimensions of free-time
      management had significant negative relationships with leisure boredom.
      Furthermore, the results of stepwise regression analysis revealed that four
      dimensions of free-time management were significant contributors to leisure
      boredom. Finally, we suggested students can avoid boredom by properly planning
      and organizing leisure time and applying techniques for managing leisure time.

PMID- 22662397
TI  - The trend toward more attractive and informative titles: American Psychologist
      1946-2010.
AB  - Titles of journal articles serve to attract attention and inform potential
      readers. All titles from 65 volumes of American Psychologist (1946-2010, N =
      12,313 titles) were studied in terms of their emotionality, style, and contents.
      Several trends noted for titles in different kinds of journals from psychology
      and other disciplines were present in American Psychologist (increasing title
      length, increasing use of punctuation marks, increasing employment of words with
      pleasant and arousing connotations, variations in the frequency of different
      content words). Longer titles allow authors to specify more information, and
      emotionally upbeat titles are more likely to attract reader attention. In an
      unexpected quadratic trend, titles became more abstract and the number of titles
      increased until about 1985, after which the trend was reversed and titles became
      more concrete as their numbers decreased. Predictors of this trend include
      societal variables and the journal's editorial policies.

PMID- 22662398
TI  - Motivational interviewing and smoking behaviors: a critical appraisal and
      literature review of selected cessation initiatives.
AB  - The present paper systematically reviewed and critically appraised three
      different dimensions of motivational interviewing currently utilized in smoking
      cessation initiatives: social support, motivation, and tailored interventions. A
      review of four databases generated 57 primary articles, 17 of which met the
      inclusion criteria of an intervention study utilizing at least one dimension of
      motivational interviewing, adults between 18 and 64 years, no comorbidities, and
      a follow-up period of at least 6 weeks. More than 11,600 participants are
      represented in this review. The implementation of social support, motivation, and
      tailored interventions yielded mixed results. Furthermore, threats to validity
      emerged, including self-report, follow-up period, sample sizes, a priori
      differences in groups, and web-based and text-based interventions. Further
      research must ascertain the efficacy of the three dimensions of motivational
      interviewing indicated by the mixed results reported in terms of statistical
      significance of cessation rates. More empirically rigorous designs with
      evaluations based on stringent replicable criteria are needed.

PMID- 22662399
TI  - Reactions to a survey among those who were and were not sexually assaulted while
      serving in the military.
AB  - Surveys are among the most common methods for evaluating military sexual assault
      experiences among members of the U.S. military; however, little research has
      examined how receiving surveys about such sexual assaults might affect
      recipients. In the present sample of 530 active duty and veteran military
      personnel, just 10% reported unexpected upset, 11% reported regretting
      participation in the survey, and 22% reported benefitting from that participation
      overall. A minority of respondents with a history of sexual assault while in the
      military reported unexpected upset, although the prevalence was three times
      higher than that of participants without such history (24% vs 8%). There were no
      statistically significant differences in perceived regret and benefit of
      participation in the survey between those with and without a history of sexual
      assault while in the military. Although limited in number, male military sexual
      assault survivors (n = 8) were significantly more likely than female survivors to
      report being more upset by the survey than they had anticipated. Implications for
      future research are discussed.

PMID- 22662400
TI  - Relationships among self-esteem, stress, and physical activity in college
      students.
AB  - The purpose of this study was to identify population and sex-specific
      relationships between perceived stress, self-esteem, and physical activity in
      college students. 90 students, ages 18 and older and enrolled in five sections of
      a health and human behavior class during the spring 2010 semester, were contacted
      for this study with 74 consenting to serve as study participants. Each
      participant completed three surveys: the Rosenberg Self-Esteem Scale, the
      Perceived Stress Scale, and the International Physical Activity Questionnaire.
      Significant correlations were observed between perceived stress and self-esteem
      in men, and in women. Physical activity was not significantly correlated with
      perceived stress or self-esteem.

PMID- 22662401
TI  - Attitudes toward psychotropic medications.
AB  - Attitudes and beliefs towards psychotropic medication were evaluated among
      psychiatric outpatients, patients receiving buprenorphine treatment for substance
      abuse, and a group who reported never having used psychotropic medications (non
      users). The Drug Attitude Inventory scale and the Beliefs about Medicines
      Questionnaire General were used to assess attitudes and beliefs of 49
      participants. Non-users exhibited more negative attitudes and beliefs toward
      psychotropic medication than both psychiatric groups.

PMID- 22662402
TI  - The Tower of London Test: different scoring criteria for diagnosing Alzheimer's
      disease and mild cognitive impairment.
AB  - The Tower of London (TOL) is used for evaluating planning skills, which is a
      component of the executive functions. Different versions and scoring criteria
      were developed for this task, and some of them present with different
      psychometrical properties. This study aimed to evaluate two specific scoring
      methods of the TOL in diagnosing Mild Cognitive Impairment and probable
      Alzheimer's disease. The TOL total scores from 60 patients of each diagnosis were
      compared with the performance of 60 healthy-aged controls using receiver
      operating characteristics analysis and multinomial logistic regression. Krikorian
      method better diagnosed Alzheimer's disease, while Portellas's was better at
      discriminating healthy controls from Mild Cognitive Impairment, but were not
      efficient at comparing this last group with Alzheimer's patients. Regression
      analysis indicates that in addition to screening tests, TOL improves the
      classification of the three groups. The results suggest the two scoring methods
      used for this task may be useful for different diagnostic purposes.

PMID- 22662403
TI  - Forgiveness in relation to attachment style and consanguine marriage in Iranian
      married individuals.
AB  - The aim of this study was to compare forgiveness in secure and insecure Iranian
      married couples. Whether marriage had occurred within the family (consanguine) or
      not (non-consanguine) was also considered. 400 married participants completed the
      Family Forgiveness Scale and the Adult Attachment Questionnaire. Analysis of
      reported forgiveness within the marital family showed that, although there was no
      significant difference between secure and insecure participants in overall
      forgiveness, secure participants rated "reparation" and "resolution" higher,
      whereas insecure participants rated "realization" and "recognition" higher.
      Comparing the experience of forgiveness in the family of origin, securely
      attached couples not only reported significantly more overall forgiveness but
      reported more "realization" and "resolution" while forgiving. Some interesting
      sex differences were also found, as individuals in consanguine vs non-consanguine
      couples differed in mean "recognition" in the forgiveness process.

PMID- 22662404
TI  - Development of a Facebook Addiction Scale.
AB  - The Bergen Facebook Addiction Scale (BFAS), initially a pool of 18 items, three
      reflecting each of the six core elements of addiction (salience, mood
      modification, tolerance, withdrawal, conflict, and relapse), was constructed and
      administered to 423 students together with several other standardized self-report
      scales (Addictive Tendencies Scale, Online Sociability Scale, Facebook Attitude
      Scale, NEO-FFI, BIS/BAS scales, and Sleep questions). That item within each of
      the six addiction elements with the highest corrected item-total correlation was
      retained in the final scale. The factor structure of the scale was good (RMSEA =
      .046, CFI = .99) and coefficient alpha was .83. The 3-week test-retest
      reliability coefficient was .82. The scores converged with scores for other
      scales of Facebook activity. Also, they were positively related to Neuroticism
      and Extraversion, and negatively related to Conscientiousness. High scores on the
      new scale were associated with delayed bedtimes and rising times.

PMID- 22662405
TI  - Facebook addiction: concerns, criticism, and recommendations--a response to
      Andreassen and colleagues.
AB  - This paper provides a brief critique of the Facebook addiction research field in
      relation to the Bergen Facebook Addiction Scale developed by Andreaessen and
      colleagues (2012). Just like the term "Internet addiction," the term "Facebook
      addiction" may already be obsolete because there are many activities that a
      person can engage in on the Facebook website (e.g., messaging friends, playing
      games like Farmville, and gambling). What is needed is a new psychometric scale
      examining potential addiction to a particular online application (i.e., social
      networking) rather than activity on a particular website (i.e., Facebook).

PMID- 22662406
TI  - Psychometric properties of Attitudes Towards Lesbians and Gay Men Scale with
      Chinese university students.
AB  - The 10-item Attitudes Towards Lesbian and Gay Men Scale was translated into
      traditional Chinese, with slight modification in item wordings (by replacing the
      words such as "lesbians" with "female homosexuals" and "gay men" with "male
      homosexuals"). Data were collected with a convenient sample of 462 Chinese
      undergraduate students in social work training programmes from three Hong Kong
      universities. Analysis of the data showed responses to the scale and its two
      subscales were internally consistent and a one-factor structure was found on the
      total scale and separately on each of its two subscales. Differences by religious
      belief and sex were observed using the total scale scores, as in previous studies
      using this scale. Researchers could consider using this scale with Hong Kong
      Chinese and in subsequent cross-cultural studies involving a wider range of
      Chinese respondents.

PMID- 22662407
TI  - Taking levels of analysis in humor more seriously: comment on Romero and Arendt.
AB  - Humor is a phenomenon that can simultaneously coexist at the individual, dyadic,
      and group levels, making its measurement and conceptualization complex. In a
      recent field study, Romero and Arendt (2011) examined relationships between four
      humor styles (i.e., affiliative, self-enhancing, aggressive, self-defeating) and
      four outcomes (i.e., stress, satisfaction with co-workers, team cooperation,
      organizational commitment), however, the latter was apparently measured as a self
      report at the individual level of analysis. Their interesting results indicated
      different humor styles can have either positive or negative effects on these
      outcome variables. However, if their operational definition--and hence their
      conceptualization--of humor is based on self-report by the initiator, it may be
      problematic to use it at the dyadic and group levels because it potentially mixes
      levels of analysis and may cause misalignment between data and theory. Cautions
      and implications for future research are discussed.

PMID- 22662408
TI  - Religious orientation and mental health: a study with Turkish university
      students.
AB  - The present study examined the relationship between religious orientation and
      mental health symptoms among Turkish students. A total of 341 undergraduate
      students between the ages of 18 and 26 completed the Brief Symptom Inventory and
      Age Universal Intrinsic-Extrinsic Scale. Extrinsic orientation was found to be
      correlated positively with symptoms of anxiety and depression. There were also
      significant correlations between hostility scores and both intrinsic and
      extrinsic religious orientations. Patterns were similar to those reported
      previously, but correlations were mostly in the .10-.14 range. In multiple
      regression models, extrinsic orientation emerged as the only significant
      predictor for hostility, anxiety, and depression; however, only 2% of the
      variance was explained.

PMID- 22662409
TI  - Demographic and occupational correlates of workaholism.
AB  - Drawing on a convenience sample of 9,160 Dutch employees, the present study
      examined whether commonly held ideas about the associations between demographic,
      professional, and occupational characteristics and workaholism would be observed.
      For example, it is sometimes assumed that managers are more likely to display
      workaholic tendencies than others. Analysis of variance was used to relate
      workaholism scores (measured as the combination of working excessively and
      working compulsively) to participant age, sex, employment status (self-employed
      or not), profession, and occupational sector. Relatively high average scores on
      workaholism were obtained by workers in the agriculture, construction,
      communication, consultancy, and commerce/trade sectors, as well as managers and
      higher professionals. Low scores were found for those in the public
      administration and services industry sectors, and for nurses, social workers, and
      paramedics. The other characteristics were not or only weakly related to
      workaholism.

PMID- 22662410
TI  - Comparison between immigrant and Spanish native-born pathological gambling
      patients.
AB  - The study compared clinical, psychopathological, and personality profiles between
      immigrants and Spanish native-born pathological gambling patients. A total of
      1,601 native-born and 133 immigrant patients attending treatment at a specialized
      hospital unit were administered a battery of questionnaires during clinical
      assessment. Outcome measures were compared between both groups and the
      incremental predictive accuracy of the area of origin was examined using a
      regression model. Native-born Spaniards showed a mean 2.6 yr. greater duration of
      the disorder, while immigrants scored higher on South Oaks Gambling Screen,
      frequency of going to casinos, and total money spent (in a single day and/or to
      recover losses). General psychopathology and personality scores did not differ
      between the cohorts. However, immigration from Asia had a statistically
      significantly incremental validity for pathological gambling in South Oaks
      Gambling Screen scores. Both cohorts shared more similarities than differences in
      their gambling profiles.

PMID- 22662411
TI  - Psychometric properties of a four-component Norwegian Organizational Justice
      Scale.
AB  - Organizational justice has attracted attention as a predictor of employees'
      mental and physical health as well as commitment and work outcomes. The lack of a
      Norwegian translation of an organizational justice scale has precluded its use in
      Norway. Four dimensions of the organizational justice construct were examined in
      a Norwegian military context, including facet measures of distributional,
      interpersonal, and informational justice developed by Colquitt in 2001, in
      addition to procedural justice developed by Moorman in 1991. Confirmatory factor
      analyses supported a four-dimensional structure with good internal consistency.
      Follow-up analyses have suggested that the four dimensions were nested beneath a
      general, latent organizational justice factor. A positive relationship between
      organizational justice and self-sacrificial behavior was found, indicating
      satisfactory construct validity. The results demonstrate that the Norwegian
      Organizational Justice Scale is a reliable and construct-valid measure of
      organizational justice in a Norwegian setting.

PMID- 22662412
TI  - A confirmatory factor analytic approach on perceptions of knowledge and skills in
      teaching (PKST).
AB  - This paper reports the cross-validation of the factor pattern of the Perceptions
      of Knowledge and Skills in Teaching (PKST) survey, which was used to assess the
      self-perceived pedagogical knowledge and skills of pre-service and beginning
      teachers. The sample comprised 323 pre-service teachers enrolled in a 1-yr. post
      graduate teacher education program in Singapore. The survey had 37 items
      distributed across six scales: student learning, lesson planning, instructional
      support, accommodating diversity, classroom management, and care and concern. A
      confirmatory factor analysis (CFA) was used to cross-validate the survey's factor
      pattern. The results showed that the model was an acceptable fit to the data. The
      PKST survey can thus be adapted by different teacher education programs to assess
      pre-service and beginning teachers' progress in developing their pedagogical
      knowledge and skills.

PMID- 22662413
TI  - Investigation of the two-factor model for the English version of the need for
      closure scale.
AB  - Using the English version of the Need for Closure Scale, this research
      investigated previous, though largely ignored, recommendations to exclude the
      close-mindedness subscale and to treat the Need for Closure Scale as a two-factor
      (vs single-factor) scale. Reliability and correlational analyses supported the
      recommendation to exclude close-mindedness. The two-factor model without close
      mindedness yielded better fit indexes than a single-factor model or a two-factor
      model with close-mindedness. Despite the strong cross-cultural use of the scale,
      no investigation had yet tested the two-factor model without close-mindedness
      using any language other than Dutch. The present results and discussion can
      improve the study of need for closure by encouraging more researchers to consider
      the supported recommendations. Roets and Van Hiel's proposed modification to make
      the Need for Closure Scale a single-factor scale was also discussed.

PMID- 22662414
TI  - Effect of group means on the probability of consensus.
AB  - In this study, groups who could not reach a consensus were investigated using the
      group polarization paradigm. The purpose was to explore the conditions leading to
      intragroup disagreement and attitude change following disagreement among 269
      participants. Analysis indicated that the probability of consensus was low when
      the group means differed from the grand mean of the entire sample. When small
      differences among group members were found, depolarization (reverse direction of
      polarization) followed disagreement. These results suggested the groups which
      deviated most from the population tendency were the most likely to cause within
      group disagreement, while within-group variances determined the direction of
      attitude change following disagreement within the group.

PMID- 22662415
TI  - Sex-role orientation and attachment styles of sex offenders.
AB  - Given the increase of individuals who have a history of sexual offenses, there
      has been an increase in research on the etiology of sex-offending behavior. The
      present purpose was to evaluate the relationship between sex-role orientation and
      attachment styles of males who were sex offenders. Analysis yielded statistically
      significant differences between comparison (n = 22) and clinical groups (n = 21)
      in gender roles, with little sign of the androgynous gender type for sex
      offenders. The offender group showed significantly lower frequency of androgyny
      scores and significantly higher scores on feminine and undifferentiated
      orientations, supporting the theoretical view of sex offenders as being "cross
      sex-typed." In addition, the sex offender group had a significantly higher mean
      score on anxious-avoidant relationship attachment. Based on the present findings,
      there appears to be a need to help sex offenders explore how their gender roles
      may relate to their sex-offending behavior and assist sex offenders in the
      development of adaptive relationships with reduced anxiety and ambivalence.

PMID- 22662416
TI  - An investigation of self-assessment bias in mental health providers.
AB  - Previous research has consistently found self-assessment bias (an overly positive
      assessment of personal performance) to be present in a wide variety of work
      situations. The present investigation extended this area of research with a multi
      disciplinary sample of mental health professionals. Respondents were asked to:
      (a) compare their own overall clinical skills and performance to others in their
      profession, and (b) indicate the percentage of their clients who improved,
      remained the same, or deteriorated as a result of treatment with them. Results
      indicated that 25% of mental health professionals viewed their skill to be at the
      90th percentile when compared to their peers, and none viewed themselves as below
      average. Further, when compared to the published literature, clinicians tended to
      overestimate their rates of client improvement and underestimate their rates of
      client deterioration. The implications of this self-assessment bias for
      improvement of psychotherapy outcomes are discussed.

PMID- 22662418
TI  - Effects of gaze and speech rate on receivers' evaluations of persuasive speech.
AB  - This study examined how gaze and speech rate affect perceptions of a speaker.
      Participants viewed a video recording of one of four persuasive messages
      delivered by a female speaker. Analysis of speech rate, gaze, and listener's sex
      revealed that when combined with a small amount of gaze, slow speech rate
      decreased trustworthiness as compared to a fast speech rate. For women, slow
      speech rate was thought to be indicative of less expertise as compared to a fast
      speech rate, again when combined with low gaze. There were no significant
      interactions, but there were main effects of gaze and speech rate on
      persuasiveness. High levels of gaze and slow speech rate each enhanced
      perceptions of the speaker's persuasiveness.

PMID- 22662417
TI  - Race/ethnicity and mental health in the first decade of the 21st century.
AB  - Recent empirical studies on mental health generally report racial/ ethnic
      differences in depression rates but typically do not control for potential
      confounding by sample contextual variations in historical epoch, geographical
      location, and social demography. An empirical study of race/ethnicity differences
      in psychological distress is reported as an attempt to control these contexts by
      using a sample that is homogeneous in age, historical epoch, geography, and
      social demography (954 youth ages 18-19 living in a single, large urban
      community). No mean differences in psychological distress were observed among
      four racial/ethnic groups: Asians, African Americans, Latinos, and non-Hispanic
      Whites. A second analysis compared 17 different racial/ethnic groups defined in
      terms of family national origin. No differences in psychological distress were
      found among these groups. The findings are consistent with the view that
      race/ethnicity itself is not related to disparities in mental health.

PMID- 22662419
TI  - Dimensionality of organizational justice in a call center context.
AB  - Summary.-Employees in three call centers were surveyed about their perceptions of
      organizational justice. Four factors were measured: distributive justice,
      procedural justice, interpersonal justice, and informational justice. Structural
      equation modeling was employed to test whether a two-, three-, or four-factor
      model best fit the call center data. A three-factor model of distributive,
      procedural, and informational justice provided the best fit to these data. The
      three-factor model that showed the best fit does not conform to any of the more
      traditional models identified in the organizational justice literature. This
      implies that the context in which organizational justice is measured may play a
      role in identifying which justice factors are relevant to employees. Findings add
      to the empirical evidence on the dimensionality of organizational justice and
      imply that dimensionality of organizational justice is more context-dependent
      than previously thought.

PMID- 22662420
TI  - Turkish adolescents' loneliness.
AB  - The goal of this study was to characterize loneliness among adolescents with
      respect to socioeconomic level, sex, and mothers' and fathers' education. General
      information about the 400 adolescents and their families were obtained. The UCLA
      Loneliness Scale was administered. Results of a hierarchical multiple regression
      showed that mothers' educational level explained a slight but statistically
      significant amount of variance in adolescents' loneliness scores while sex,
      socioeconomic level and fathers' educational level did not.

PMID- 22662421
TI  - Victorian graduate disheartened.

PMID- 22662422
TI  - Student dilemma.

PMID- 22662423
TI  - Closing the gap but long way to go.

PMID- 22662424
TI  - Budget cuts hit home.

PMID- 22662425
TI  - There's a lot of hot air about wind farms.

PMID- 22662426
TI  - University nurse education--ethics or ideology?

PMID- 22662427
TI  - Changing the face of health care electronically.

PMID- 22662428
TI  - Enrolled nurse trainees in acute care.
AB  - Enrolled nurses (ENs) play a pivotal role in the health workforce in Australia
      and the role is expanding in many practice settings. An EN traineeship was
      introduced in an acute medical/surgical setting at St Vincents & Mercy Private
      Hospital (STVMPH) a large metropolitan private hospital in Victoria, in 2005.
      Since then there has been a significant increase in the EN workforce across all
      clinical areas within the organisation. With consideration of skill mix the
      current percentage of 18.3% of the nursing workforce is ENs. This review shows
      the viability of such a program in relation to workforce planning and
      recruitment. Enrolled nurses are a valuable source in the health care
      environment. The latest figures indicate there are 230,192 registered nurses
      (RNs) and 52, 895 ENs (Australian Institute of Health and Welfare, 2010).
      Enrolled nurses account for approximately 23% of the nursing workforce. The
      common setting for education (clinical placement) and employment for ENs is aged
      care. Education and employment of ENs in acute hospital settings is necessary to
      broaden the skill mix of nursing staff in an acute environment. The acute medical
      setting encourages ENs to develop and advance their clinical skills to practice
      acute nursing care within their scope of practice.

PMID- 22662429
TI  - Reflections...of a graduate registered nurse.

PMID- 22662430
TI  - Tackling obesity in adolescence.

PMID- 22662432
TI  - My workplace.

PMID- 22662431
TI  - CALNOC demonstrates leadership in nursing outcomes research.

PMID- 22662433
TI  - New tools to help nurses support their mentally ill clients to quit.

PMID- 22662434
TI  - Complementary and alternative medicine in midwifery practice.

PMID- 22662435
TI  - Integrative medicine--a way to enhance nursing care.

PMID- 22662436
TI  - Male cancer patients turn to alternative treatment.

PMID- 22662437
TI  - Reducing the side effects of chemotherapy.

PMID- 22662438
TI  - Natural therapies.

PMID- 22662439
TI  - Administer one puppet PRN.

PMID- 22662440
TI  - Relaxation and conventional medicine go hand-in-hand.

PMID- 22662441
TI  - Have your say in a healthier and safer workplace.

PMID- 22662442
TI  - Many private providers exemplify bill's pitfalls.

PMID- 22662444
TI  - Leadership is more important than staffing levels, says Lansley.

PMID- 22662443
TI  - RCN calls for national care homes guidance as staff report failings.

PMID- 22662446
TI  - Regulator jettisons HCA work to concentrate on fitness to practise.

PMID- 22662445
TI  - Trust funds nurses' top-up degrees in bid to win award for excellence.

PMID- 22662447
TI  - Focus on positive experiences proves uplifting for hospital staff.

PMID- 22662448
TI  - Strategic thinking.
AB  - As part of the Care campaign, nurse leaders and patients' representatives drew up
      ten 'priorities for action' that should be implemented by all healthcare
      providers. Second on the list is ensuring staffing levels are adequate. This
      article shows there is increasing understanding of the direct link between
      numbers of nursing staff and quality of care. Evidence-based tools are vital,
      given the imperative to ensure patient safety in a time of cost-cutting.

PMID- 22662449
TI  - Higher staffing levels reduce falls rate.

PMID- 22662450
TI  - Scarred for life.
AB  - Thousands of girls in the UK are at risk of female genital mutilation. A multi
      agency safeguarding group in Bristol, established after a school nurse became
      concerned that pupils were at risk, is preventing girls from being taken out of
      the country to have the procedure. It raises awareness among professionals and
      supports families in the Sudanese and Somalian communities to speak out against
      the practice.

PMID- 22662451
TI  - A humbling experience.
AB  - In February 2009, retired nurse Sir Stephen Moss was appointed as a non-executive
      board director at Mid Staffordshire NHS Foundation Trust, which was under
      investigation for poor care. Two weeks later a damning Healthcare Commission
      report revealed the full extent of Stafford Hospital's failings. Sir Stephen went
      on to chair the trust's board until January. He describes what the hospital was
      like and how it has changed, how he tackled the challenge, and how the experience
      affected him

PMID- 22662452
TI  - Implementing structured preceptorship in an acute hospital.
AB  - The term preceptorship has been used in the NHS to describe newly registered
      practitioners' transition from novice to expert under the guidance of an
      experienced practitioner. This article describes the implementation of a
      preceptorship course in The Newcastle upon Tyne Hospitals NHS Foundation Trust.
      The course is based on the core dimensions of the NHS Knowledge and Skills
      Framework and has received academic accreditation from Northumbria University.

PMID- 22662453
TI  - Recording violent incidents in the emergency department.
AB  - AIM: To evaluate the quality of record-keeping by nursing staff after violent
      incidents in one emergency department in the UK. METHOD: This study was
      undertaken between August 2007 and May 2009 in the emergency department of one
      acute NHS hospital. A retrospective documentary analysis of violent incident
      forms completed by nursing staff (n = 38), semi-structured interviews (n = 9) and
      periods of non-participatory, unstructured general observation (52 hours) was
      conducted. FINDINGS: From the documentary analysis, 25 incident forms (n = 38,
      66%) were incomplete or lacking detail. Semi-structured interviews with study
      participants suggested that many violent incidents went unreported. It was widely
      accepted by the participants that the reporting process did not capture the
      reality of clinical practice, and the lack of a robust reporting process
      suggested that incident reporting was seen as a low priority. CONCLUSION: This
      study's findings support those of previous studies examining the quality of
      record-keeping in clinical practice. Poor record-keeping is a common breach of
      the Nursing and Midwifery Council code of conduct, potentially compromising
      patient safety. Strategies need to be formulated to improve record-keeping.
      Avoiding individual blame and consideration of the working environment may
      encourage staff to complete incident forms.

PMID- 22662454
TI  - Caring for frail patients: best practice.
AB  - Frailty has become synonymous with vulnerability and is a state caused by many
      factors, including disability, recurrent infection and multiple co-morbidities.
      The Gwent frailty service recognises the importance of an interdisciplinary
      approach to care, including timely recognition of frailty in patients and
      referral to the most appropriate services to optimise management and treatment.

PMID- 22662455
TI  - Cellulitis.

PMID- 22662456
TI  - Mentoring the mentors.

PMID- 22662457
TI  - Improvement through inspection.

PMID- 22662459
TI  - The time has come.

PMID- 22662458
TI  - Time for a reality check.

PMID- 22662460
TI  - Frequently asked practice questions: a summary of CARNA practice consultations.

PMID- 22662461
TI  - Lost in translation. Informatics: the buzzword in health care today.

PMID- 22662462
TI  - Changing the culture of care in NICU.

PMID- 22662463
TI  - Stroke, dysphagia and oral care: what is best practice?

PMID- 22662464
TI  - Erecting pillars for the registered nurse community.

PMID- 22662465
TI  - The new roadmap.

PMID- 22662466
TI  - Dendrites, axons, and G.V. Black.

PMID- 22662467
TI  - A source of new patients.

PMID- 22662468
TI  - Extension for prevention: margin placement.
AB  - This article will review the concept of extension for prevention popularized by
      G.V. Black around the early 1900s. Concepts of extension and prevention have
      changed over the years with a more informed knowledge of the caries process,
      improved materials, cutting instruments, and techniques. The reasons for
      placement of the outline form relative to the tooth morphology, gingival tissue,
      relationship to adjacent teeth, and the choice of material will be described for
      all of the materials used in restorative dentistry. Research will be cited to
      support the scientific basis for outline form placement.

PMID- 22662469
TI  - Touching lives through smiles: Minnesota's first-ever Mission of Mercy.

PMID- 22662470
TI  - Treatment of oral candidiasis.

PMID- 22662471
TI  - Addressing change: the 2012 MDA president's interview.

PMID- 22662472
TI  - A rebirth of Dr. Painless Parker?

PMID- 22662473
TI  - WE DAT ... the LDA!

PMID- 22662474
TI  - PEW report worth heeding for several reasons.

PMID- 22662475
TI  - Interview with the President Elect: Dr. Edward Hebert.

PMID- 22662476
TI  - To convert or not to convert: that is the IRA question The new Roth IRA
      conversion opportunity.

PMID- 22662477
TI  - Louisiana State Board of Dentistry.

PMID- 22662478
TI  - Med reductions boost quality of life: A facility challenges the common practice
      of prescribing multiple drugs for the elderly, resulting in more caregiver time
      with patients.

PMID- 22662479
TI  - Right-size staff a good bet: A staffing expert offers advice on how to ensure a
      facility has the right staff at the right time.

PMID- 22662480
TI  - Nature & nurture unite: A fan of evidence-based design makes a compelling
      argument for getting residents closer to nature.

PMID- 22662481
TI  - Prescribers a part of Tennessee's Rx drug solution.

PMID- 22662482
TI  - Underprescribing can be a "real pain" for many.

PMID- 22662483
TI  - The perfect storm: why Tennessee has the ingredients for the disaster of
      prescription drug abuse.

PMID- 22662484
TI  - DEA number needed on controlled substance prescriptions?

PMID- 22662485
TI  - Overprescribing in Tennessee: put a lid on it.

PMID- 22662486
TI  - TN doctors fully engaged in solutions to curtail Rx drug abuses.

PMID- 22662487
TI  - Too much? The TMA Public Health Committee examines overprescribing, part I:
      antibiotics.

PMID- 22662488
TI  - Improving accuracy in death certification, or, everybody dies of cardiopulmonary
      arrest.

PMID- 22662489
TI  - On being a doctor: rounding up the usual suspects.

PMID- 22662490
TI  - A stitch in time may save nine! Know the ins and outs of workers' comp.

PMID- 22662491
TI  - 401(k) changes will help physicians better understand their practice retirement
      plans.

PMID- 22662492
TI  - Access to heart disease and stroke care in Tennessee.
AB  - Tennessee is ranked fourth-worst in the United States for deaths caused by stroke
      and third-worst in the nation for cardiovascular deaths. Two recent surveys
      provide information about the geographic distribution of hospital-based, primary
      and secondary care promotion, and of emergency medical services for these disease
      conditions. This article is a synthesis of selected findings from these surveys
      to identify priority populations for interventions to reduce cardiac and stroke
      mortality in Tennessee. Twenty-three counties have a medical facility with a
      formal clinical pathway or system for implementing cardiovascular disease
      prevention strategies. Sixty-three of the state's 95 counties have no designated
      specialty center for an EMS service to transport cardiac and stroke patients.
      Fifty-six counties, comprising 38 percent of the state's population, lie between
      20 and 50 miles from the nearest state-of-the-art stroke care. Twenty-one
      counties, containing nearly 10 percent of the state's population, are greater
      than 50 miles from advanced stroke care facility. Some health districts are
      faring better than the state proportion (86.8 percent) for people indicating they
      would call 911 for a suspected cardiac or stroke emergency, while many are
      performing much poorer. The Shelby district (Memphis) is much higher (p < 0.01),
      while Madison and South Central districts are well below the state's prevalence
      (p < 0.001). The fact that these "less-likely-to-call-911" areas are also in
      mostly rural settings poses priority challenges for public education. To combat
      this trend, coordinated efforts are in progress to incentivize the development of
      cardiac and stroke centers or, alternatively, the formation of regional
      collaborative networks affiliated with a specialty center.

PMID- 22662493
TI  - Beyond integration and microgap: the compromised esthetic zone.

PMID- 22662494
TI  - Diagnostic discussion. Cherubism.

PMID- 22662495
TI  - Conquer email overload with better habits and etiquette.

PMID- 22662496
TI  - Communication is the key to a healthier work environment.

PMID- 22662497
TI  - Beyond the basics in digital photography.

PMID- 22662498
TI  - Like a wounded squirrel, legislative advocacy is part of life.

PMID- 22662499
TI  - Emergency room dental care? It doesn't make dollars and sense.

PMID- 22662500
TI  - Hooton family travels for both fun and service.

PMID- 22662501
TI  - Workers' compensation coverage.

PMID- 22662502
TI  - Online discount deals: are they a good marketing idea?

PMID- 22662503
TI  - Establishing a personal family office.

PMID- 22662504
TI  - How to see the trees for the forest: introduction to a special issue on causation
      and disease.
AB  - This paper summarizes the results from the first European Advanced Seminar in the
      Philosophy of the Life Sciences, which was held at the Brocher Foundation in
      Hermance (Switzerland) 6-10 September 2011. The Advanced Seminar brought together
      philosophers of the life sciences to discuss the topic of "Causation and
      Disease." The search for causes of disease in the biomedical sciences, we argue
      on the basis of the contributions to this conference, has not resulted in a
      simplification and unification of biomedical knowledge, as once hoped for by
      philosophers of science, but rather in its "complexification."

PMID- 22662505
TI  - The limits of reductionism in the life sciences.
AB  - In the contemporary life sciences more and more researchers emphasize the "limits
      of reductionism" (e.g. Ahn et al. 2006a, 709; Mazzocchi 2008, 10) or they call
      for a move "beyond reductionism" (Gallagher/Appenzeller 1999, 79). However, it is
      far from clear what exactly they argue for and what the envisioned limits of
      reductionism are. In this paper I claim that the current discussions about
      reductionism in the life sciences, which focus on methodological and explanatory
      issues, leave the concepts of a reductive method and a reductive explanation too
      unspecified. In order to fill this gap and to clarify what the limits of
      reductionism are I identify three reductive methods that are crucial in the
      current practice of the life sciences: decomposition, focusing on internal
      factors, and studying parts in isolation. Furthermore, I argue that reductive
      explanations in the life sciences exhibit three characteristics: first, they
      refer only to factors at a lower level than the phenomenon at issue, second, they
      focus on internal factors and thus ignore or simplify the environment of a
      system, and, third, they cite only the parts of a system in isolation.

PMID- 22662506
TI  - What systems biology can tell us about disease.
AB  - A recent debate has touched upon the question of whether diseases can be
      understood as dysfunctional mechanisms or whether there are "pathological"
      mechanisms that deserve to be investigated and explained independently (Nervi
      2010; Moghaddam-Taaheri 2011). Here I suggest that both views tell us something
      important about disease but that in many instances only a systemic view can shed
      light on the relationship between physiology and pathology. I provide examples
      from the literature in systems biology in support of my position. As a result of
      my analysis, I conclude that a perspective narrowly focusing on mechanisms is
      insufficient if the goal is to get a comprehensive picture of disease.

PMID- 22662507
TI  - Genetic susceptibility to a complex disease: the key role of functional
      redundancy.
AB  - Complex diseases involve both a genetic component and a response to environmental
      factors or lifestyle changes. Recently, genome-wide association studies (GWAS)
      have succeeded in identifying hundreds of polymorphisms that are statistically
      associated with complex diseases. However, the association is usually weak and
      none of the associated allelic forms is either necessary or sufficient for the
      disease occurrence. We argue that this promotes a network view, centred on
      functional redundancy. We adapted reliability theory to the concerned sub
      network, modelled as a parallel array of functional modules. In our model, as
      long as one module remains active, the function correlated with the respective
      disease is ensured and disease does not occur. Genetic factors reduce the initial
      number of available modules while environment, contingent surroundings, personal
      history, epigenetics, and some intrinsic stochasticity influence their
      persistence time. This model reproduces age-specific incidence curves and
      explains the influence of environmental changes. It offers a new paradigm,
      according to which disease occurs due to a lack of functional elements, depending
      on many idiosyncratic factors. Genetic risk assessed from GWAS is only a
      statistical notion with no direct interpretation at the individual level.
      However, genomic profiling could be useful at population level in devising models
      to guide decisions in health care policy.

PMID- 22662508
TI  - Hierarchies and causal relationships in interpretative models of the neoplastic
      process.
AB  - The aim of this paper is to present a critical analysis of the kind of biological
      systems identified in the main explanatory theories of cancer (i.e. Somatic
      Mutation Theory and Tissue Organization Field Theory) and how references to the
      hierarchical organization of these biological systems are used in their
      explanatory arguments. I will discuss these aspects in terms of the isolation of
      the "locus of control" (Bechtel and Richardson 2010); that is, the point at which
      decisions are made shaping the explanatory endeavour. In fact, the current view
      of the neoplastic process, not as a static circumstance but as an evolving
      molecular and cellular process, makes it evident that the choice of the right
      level of analysis is not self-evident. This focus clarifies some epistemological
      reasons for the divergence between reductionist and organicist accounts and seems
      to suggest that the basis for distinctions among causal relationships that
      scientists sometimes make can be found in the hierarchical character of complex
      biological systems. I will argue that these different causal relationships
      reflect different levels of epistemic concern.

PMID- 22662509
TI  - Making sense of downward causation in manipulationism: illustrations from cancer
      research.
AB  - Many researchers consider cancer to have molecular causes, namely mutated genes
      that result in abnormal cell proliferation (e.g. Weinberg 1998). For others, the
      causes of cancer are to be found not at the molecular level but at the tissue
      level where carcinogenesis consists of disrupted tissue organization with
      downward causation effects on cells and cellular components (e.g. Sonnenschein
      and Soto 2008). In this contribution, I ponder how to make sense of such downward
      causation claims. Adopting a manipulationist account of causation (Woodward
      2003), I propose a formal definition of downward causation and discuss further
      requirements (in light of Baumgartner 2009). I then show that such an account
      cannot be mobilized in support of non-reductive physicalism (contrary to
      Raatikainen 2010). However, I also argue that such downward causation claims
      might point at particularly interesting dynamic properties of causal
      relationships that might prove salient in characterizing causal relationships
      (following Woodward 2010).

PMID- 22662510
TI  - Epistemic causality and evidence-based medicine.
AB  - Causal claims in biomedical contexts are ubiquitous albeit they are not always
      made explicit. This paper addresses the question of what causal claims mean in
      the context of disease. It is argued that in medical contexts causality ought to
      be interpreted according to the epistemic theory. The epistemic theory offers an
      alternative to traditional accounts that cash out causation either in terms of
      "difference-making" relations or in terms of mechanisms. According to the
      epistemic approach, causal claims tell us about which inferences (e.g., diagnoses
      and prognoses) are appropriate, rather than about the presence of some physical
      causal relation analogous to distance or gravitational attraction. It is shown
      that the epistemic theory has important consequences for medical practice, in
      particular with regard to evidence-based causal assessment.

PMID- 22662511
TI  - How to make sense of broadly applied medical classification systems: introducing
      epistemic hubs.
AB  - What are medical classification systems good for? Taking this question as a
      starting point, this paper argues that different answers have to be given
      depending on the scope of application of the classification system. While the use
      of restricted and specialised classification systems can be described rather well
      with the existing scientific taxonomy account, this account falls short to make
      sense of the function that systems play that are heterogeneous and imprecise but
      broadly applied, such as the International Statistical Classification of Diseases
      and Health-Related Problems (ICD). Given that the causal complexity and inter
      individual heterogeneity of disease manifestation and progression challenge
      obtaining unambiguous, universally applicable definitions of the units of
      classification, this paper aims to introduce a pluralist account that relies on
      the concept of "epistemic hubs." This epistemic hub account stresses that
      classification systems used in different settings by a variety of actors can
      mediate between them and thus provide important opportunities for exchange of
      information and integration of causal explanations. Therefore, broadly applied
      classifications have to be connective and compatible with additional use-specific
      epistemic strategies in order to facilitate interactions between different
      methodological approaches to diseases.

PMID- 22662512
TI  - Humanised models of cancer in molecular medicine: the experimental control of
      disanalogy.
AB  - This paper explores the epistemology of extrapolation from model organisms to
      humans in molecular medicine. We take into account two common views on the issue,
      the homology view and the disanalogy view. In response to both interpretations,
      we argue that the foundational basis of extrapolations cannot simply be provided
      by homology and that relevant disanalogies can, thanks to the techniques of
      molecular biology, be experimentally controlled and exploited to allow useful and
      reliable extrapolations. The case of "humanised mice" in the context of cancer
      stem cell research provides evidence of how animal models can be construed to
      approximate bona fide causal analogue models of human diseases. To supplement
      this view we show how the epistemology of model organisms needs to take into
      account the engineering side of molecular medicine. Model organisms are often
      manipulated to create analogies or remove disanalogies with the target system. We
      maintain that highlighting this feature is fundamental to explain what warrants
      extrapolation in the search for the molecular causes of disease.

PMID- 22662513
TI  - MI often presents without chest pain in women.

PMID- 22662514
TI  - Postmenopausal bleeding should be referred urgently.
AB  - Postmenopausal bleeding is an episode of bleeding 12 months or more after the
      last menstrual period. It occurs in up to 10% of women aged over 55 years. All
      women with postmenopausal bleeding should be referred urgently. Endometrial
      cancer is present in around 10% of patients; most bleeding has a benign cause.
      The peak incidence for endometrial carcinoma is between 65 and 75 years of age.
      Causes of postmenopausal bleeding include: endometrial carcinoma; cervical
      carcinoma; vaginal atrophy; endometrial hyperplasia +/- polyp; cervical polyps;
      hormone-producing ovarian tumours; haematuria and rectal bleeding. The aim of
      assessment and investigation of postmenopausal bleeding is to identify a cause
      and exclude cancer. Assessment should start by taking a detailed history, with
      identification of risk factors for endometrial cancer, as well as a medication
      history covering use of HRT, tamoxifen and anticoagulants. Abdominal and pelvic
      examinations should be carried out to look for masses. Speculum examination
      should be performed to see if a source of bleeding can be identified, assess
      atrophic changes in the vagina and look for evidence of cervical malignancy or
      polyps. Ultrasound scan and endometrial biopsy are complementary. Ultrasound scan
      can define endometrial thickness and identify structural abnormalities of the
      uterus, endometrium and ovaries. Endometrial biopsy provides a histological
      diagnosis. The measurement of endometrial thickness aims to identify which women
      with postmenopausal bleeding are at significant risk of endometrial cancer. If
      the examination is normal, the bleeding has stopped and the endometrial thickness
      is < 5 mm on transvaginal ultrasound scan, no further action need be taken.

PMID- 22662515
TI  - Which patients should be offered caesarean section?
AB  - Caesarean section (CS) rates have steadily risen from 10% of all deliveries in
      the 1980s to a current figure of around 23.8%. Approximately 75% of CS are
      emergency procedures and only 25% are elective planned deliveries. When deciding
      whether to offer CS, it is important to consider the psychological implications
      for the patient as well as the physical and mental sequelae in future
      pregnancies. Clinicians should provide pregnant women with evidence-based
      information and support. Information should include details about the true
      indication(s) for the CS and what it implies, including its risks and benefits.
      The updated NICE guideline does not advocate CS in uncomplicated pregnancies.
      However, it supports CS on maternal request when attempts to empower the mother
      to have a vaginal birth have not been successful. CS on maternal request only
      represented 1.4% of all CS in 2001. CS may reduce perineal and abdominal pain
      during birth and 3 days postpartum. It may also reduce injury to the vagina,
      early postpartum haemorrhage and obstetric shock. The following patients should
      be offered a planned elective CS: singleton breech presentation at term, after
      external cephalic version has failed, has been declined or is contraindicated;
      multiple pregnancies when the first twin is not cephalic; placenta praevia, minor
      or major, (close to or covering the os); HIV-positive women who are not on any
      antiretroviral therapy, have a high viral load or co-infection with hepatitis C
      irrespective of viral load; and women with primary genital herpes simplex virus
      infection occurring in the third trimester.

PMID- 22662516
TI  - Following up patients after treatment for anaphylaxis.
AB  - Anaphylaxis is defined as a severe, life-threatening, generalised or systemic
      hypersensitivity reaction. Diagnosis is based on the presenting symptoms and
      signs which classically develop rapidly, typically evolving over minutes but in
      some cases hours. Various combinations of airway and/or breathing and/or
      circulatory problems are possible, as well as urticaria, and hypotension. Skin
      and/or mucosal changes (typically urticaria and/or angioedema) are seen in around
      75% of cases, but importantly these features alone are insufficient for a
      diagnosis of anaphylaxis. As soon as possible after successful emergency
      treatment, timed blood samples should be taken for the mast cell tryptase (MCT)
      test. Serum samples need to be taken within 1-2 hours but no later than 4 hours
      from the onset of symptoms. It is important to document the acute clinical
      features (record BP, respiratory rate etc) and the time course of the onset of
      symptoms/signs and their resolution. Because of the risk of relapse patients
      should be observed for 6-12 hours after the onset of symptoms. Children under 16
      years should be admitted and supervised by a paediatrician. An adrenaline
      injector device for intramuscular use only, should be prescribed as an interim
      measure before referral to a specialist allergy clinic. Referral to a specialist
      allergy service (or specialist paediatric service), is strongly recommended.
      Diagnosis can be confirmed, and further investigations organised.

PMID- 22662517
TI  - Scaley skin conditions.

PMID- 22662518
TI  - Radium water, and radio-oxygen, therapy in rheumatism. 1912.

PMID- 22662519
TI  - The healing touch.

PMID- 22662521
TI  - Trusts told they can slash nurse budgets.

PMID- 22662520
TI  - "The regulator must not be seen as an HR service".

PMID- 22662522
TI  - "Insufficient staffing makes good care nigh on impossible".

PMID- 22662523
TI  - "What would you do if asked for health advice on Twitter?".

PMID- 22662524
TI  - Creating a culture to deliver compassionate care.
AB  - The Delivering Dignity report by the Commission on Dignity in Care for Older
      People provides direction on how to improve care for older people, but a better
      understanding is needed of how to develop sustainable cultural change.

PMID- 22662526
TI  - An overview of chronic heart failure management.
AB  - The prevalence of chronic heart failure is set to increase due to the growing
      ageing population. Nurses in all settings have a vital role in supporting
      patients in managing their condition. This article discusses the physiology of
      the heart, the causes and pathophysiology of heart failure, and treatment and
      management options.

PMID- 22662525
TI  - Using ambulatory A&E care to cut admissions.
AB  - Evidence shows many conditions can be effectively managed out of hospital, with
      greater patient satisfaction and fewer hospital admissions. South Tyneside
      Foundation Trust ran a pilot project in which an ambulatory emergency care (AEC)
      department saw patients admitted to hospital via their GP, producing the benefits
      stated above.

PMID- 22662527
TI  - Abdominal pain in children with pneumonia.

PMID- 22662528
TI  - Transforming emergency cardiac treatment.
AB  - NHS Improvement led the rollout of a network of primary percutaneous coronary
      intervention centres around the country, to treat patients with ST-segment
      elevation myocardial infarction. This article discusses the background,
      implementation and outcomes.

PMID- 22662529
TI  - 60 seconds with Alison While.

PMID- 22662530
TI  - Happy staff, healthy patients.

PMID- 22662531
TI  - When data reflects badly on your staff.

PMID- 22662532
TI  - Evidence should enable informed decision making, not limit choice.

PMID- 22662533
TI  - Before we begin. The importance of antenatal education.
AB  - A review of the impact of universal antenatal education found that group based
      programmes which promote the transition to parenthood by focusing on
      relationships (between the couple and with the baby), and which are participative
      and build social support, are most likely to be effective (McMillan et al 2009).
      An Expert Reference Group convened by the Department of Health has designed a
      Preparation for Birth and Beyond programme to incorporate the evidence about what
      works and which draws on neurology, sociology and psychology including theories
      about fetal programming, social capital, self-efficacy, adult learning and health
      promotion. Learning from the Family Nurse Partnership, the PBB programme builds
      on parents' strengths and their intrinsic motivation to be the best parents they
      can for their children.

PMID- 22662534
TI  - 4Children for parents and for midwives.
AB  - This article outlines the launch of a new website which will bring together the
      rich, but sometimes difficult to access, body of best practice, research and
      evidence, that parents and professionals need when dealing with children aged
      from birth-five. The article sets out the scale, type and quality of information
      that is available, highlights what midwives could helpfully share with parents to
      help them deal with their children's developments, and what they could access
      themselves to develop their practice and ensure they remain as up to date as
      possible with early years developments.

PMID- 22662535
TI  - Talkback: a strategic approach to working with maternity service users.
AB  - This paper describes the implementation of a strategic approach to service user
      involvement in Stockport, demonstrating a strong culture of collaborative
      working, between service users, providers and commissioners. It explains the
      process we used and how we learn from the stories that parents share, enabling us
      to build on the strengths of our service and develop those areas which are
      highlighted as not meeting the needs of families. It describes the establishment
      of a Service User Forum and the subsequent launch of the MSLC, with service users
      forming approximately 75 per cent of the membership. It is an influential and
      well informed voice which continues to help change our service for the better. It
      ensures that what is important to women and theirfamilies lies at the centre of
      all we do.

PMID- 22662536
TI  - Self evaluation: a specific session.

PMID- 22662537
TI  - Midwives, labour induction and the Wooden Spoon award Part 2.
AB  - Rates of labour induction without clear medical indication have risen
      exponentially. This trend has not been without consequence of increased perinatal
      mortality and morbidity. Midwives must understand the importance of educating
      pregnant women and other obstetrical providers, about the risks associated with
      labour induction. Maternal-child health policy that minimises unnecessary
      interventions is urgently needed and prevention strategies are described in the
      second part of this article. Midwives are challenged to consider their role in
      reducing unnecessary labour inductions in a rapidly changing birth culture
      reflecting high intervention.

PMID- 22662538
TI  - Perinatal quality of life: is it important for childbearing women?
AB  - Acknowledgement of and support for women's psychological and social health and
      wellbeing across the childbearing spectrum is a core aspect of contemporary
      maternity care provision. These broader definitions of health and wellbeing have
      stimulated a growing interest in and acknowledgement of the concept of quality of
      life as important in pregnant and postnatal women. Accruing evidence would
      suggest that a number of aspects of the childbearing experience, linked to
      physiological change, physical demand, clinical events, outcomes and
      complications and emotional transition across the perinatal period, are relevant
      to a woman's perceived quality of life. In addition, those perceptions of quality
      of life may have further implications for both physical and psychological
      wellbeing. It could be argued that accurate assessment of quality of life,
      however, requires reliable tools that have been either designed for or validated
      in childbearing populations. This paper briefly presents some of the issues
      related to quality of life in pregnancy and the postnatal periods and discusses
      some of the available measures to assess quality of life in childbearing women.

PMID- 22662539
TI  - Women's and men's satisfaction with two models of antenatal education.

PMID- 22662540
TI  - Use of technology in childbirth. 7. Electronic maternity records.

PMID- 22662541
TI  - Annual Conference 2011.

PMID- 22662542
TI  - Baby let the show begin.

PMID- 22662543
TI  - Osborne's regional pay plans in tatters.

PMID- 22662545
TI  - Chancellor left out on a limb as NHS chiefs reject local bargaining.

PMID- 22662544
TI  - RCN says the case for mandatory staff levels is now overwhelming.

PMID- 22662546
TI  - Review body criticises ministers for their handling of pay freeze.

PMID- 22662547
TI  - DH to review voluntary register for healthcare assistants in three years.

PMID- 22662548
TI  - Unions call for investment as school nurses are set 17 targets.

PMID- 22662549
TI  - One nurse to seven older patients: RCN recommends a safe staff ratio.

PMID- 22662550
TI  - Free to lead, free to care.
AB  - Supporting ward managers not only improves patient outcomes, but saves the NHS
      money too. Some trusts are achieving good results by giving ward managers
      supervisory status, training and greater authority. And for this the Royal
      College of Physicians recommends a salary of 75,000 sterling pounds.

PMID- 22662551
TI  - Remote access to closer care.
AB  - Some community nurses are reluctant to use new technology, fearing it will be
      difficult to use and will take them away from patients. A recent report reveals
      that new technologies, properly introduced, can transform care and save money.
      With the Department of Health determined to reduce unnecessary face-to-face
      contact between staff and patients, change is inevitable.

PMID- 22662552
TI  - Patient weighing: standardisation and measurement.
AB  - Identification of patients with specific nutritional needs requires the use of
      appropriate weighing systems. The introduction of the Non-Automated Weighing
      Instruments Directive for equipment requiring an operator (Directive 2009/23/EC
      of the European Parliament) in hospitals in the UK has provided a framework for
      standardisation of measurement accuracy in weighing equipment. This article
      outlines the recommendations of the directive. Clinical areas in which weight
      measurements are especially relevant are identified. A summary of checks for
      local verification of weighing equipment and practice is provided. In addition,
      the importance of accurate height measurement to reduce error in derived values
      of body mass index is outlined.

PMID- 22662553
TI  - Diabetes medication incidents in the care home setting.
AB  - This article analyses data received from a Freedom of Information Act 2000
      request made to the National Patient Safety Agency in June 2010. Information was
      requested about adverse drug event reports in relation to insulin therapy and
      oral glucose-lowering agents in the care home setting. Data identified were
      reported to the National Patient Safety Agency between January 12005 and December
      312009 and were processed through the National Reporting and Learning Service.
      There were 684 reports related to insulin and 84 incidents related to oral
      glucose-lowering agents. The most common error involved wrong or unclear dose:
      173 reports for insulin, including one death, and 20 reports for oral glucose
      lowering agents. Evidence shows that residents with diabetes in care homes are at
      risk of harm from adverse drug events involving insulin and oral glucose-lowering
      agents.

PMID- 22662554
TI  - Assessment, prevention and treatment of constipation in children.
AB  - The management of constipation can often be a challenge in children who may be
      fearful of opening their bowels and who may be reluctant to sit on the toilet.
      This article focuses on guidance produced by the National Institute for Health
      and Clinical Excellence on constipation in children and young people. The
      guidance discusses successful treatment of constipation, including ensuring
      effective initial emptying of the bowel and appropriate laxative therapy.

PMID- 22662555
TI  - Inhaler technique.

PMID- 22662556
TI  - Make the connection.

PMID- 22662557
TI  - The importance of good working environments.

PMID- 22662558
TI  - Bridging the skills gap.

PMID- 22662559
TI  - Turning research into results: How nurses at a Colorado hospital use evidence to
      guide practice.

PMID- 22662560
TI  - Hazardous conditions: study links miscarriages and working with certain drugs.

PMID- 22662561
TI  - Patients' needs and electronic health data.

PMID- 22662562
TI  - Targeting the big questions: Academy nurses zero in on issues to advance policy
      and practice.

PMID- 22662563
TI  - ANA brings nursing data to the bedside: nurses can share ideas, discuss issues,
      and learn on the Nursing Quality Network.

PMID- 22662564
TI  - Putting the brakes on drowsy driving.

PMID- 22662566
TI  - A call to action for nurse scientists: NINR strategic plan's goal is to create a
      healthier nation.

PMID- 22662565
TI  - Finding the path to success in state-level APRN advocacy.

PMID- 22662567
TI  - Policies to increase spontaneous labor.

PMID- 22662568
TI  - Delirium affects 80 percent of critically ill.

PMID- 22662569
TI  - 85th president of APS Susan M. Barman.

PMID- 22662570
TI  - Walter C. Randall Lecture on Biomedical Ethics: Colleagues as a defense against
      bad science.

PMID- 22662571
TI  - Conflict resolution: how to keep everyone happy!

PMID- 22662572
TI  - Lines of accountability.

PMID- 22662573
TI  - MPs call for better safeguards for staff who raise concern.

PMID- 22662574
TI  - 'Neither witches nor angels'.

PMID- 22662575
TI  - Senior charge nurse scoops award for knowledge and skills initiative.

PMID- 22662576
TI  - On closer inspection.

PMID- 22662577
TI  - Who's fit to practise?

PMID- 22662578
TI  - Effective management of trust volunteers.
AB  - A robust, well-managed volunteer programme can help NHS trusts have a better
      patient experience, engage with local communities, and improve and maintain their
      reputations. This article looks at the benefits of involving volunteers in trust
      activities and sets out the requirements to do this effectively, to enable them
      to achieve these aims.

PMID- 22662579
TI  - New measures to improve patients' experiences of care.
AB  - This article outlines a new guidance and quality standard for patient experience.
      It focuses on the generic patient experience and is aimed at all clinical and non
      clinical staff providing services for adults in NHS settings. The guidance
      focuses on improving the patient experience and has been developed by the
      National Clinical Guideline Centre as part of a National Institute for Health and
      Clinical Excellence-commissioned portfolio of work. To support this aim, it
      includes quality statements that provide benchmarks against which staff can
      measure the care they deliver.

PMID- 22662580
TI  - The role of a research nurse in translating evidence into practice.
AB  - This article describes the role and experiences of a research nurse working with
      a nursing team to implement best practice guidelines. The structure of the
      research project and resources were found to support the change, resulting in
      better patient care. Challenges promoting change as part of a research project
      included inflexibility of research paperwork and competing local trust
      priorities. The research nurse was able to support the clinical team to implement
      change through education and regular visits to the ward to monitor progress and
      feedback good practice.

PMID- 22662581
TI  - Measuring research workload to support resource planning.
AB  - Clinical research is inherent in clinical practice and recent changes to how
      medical research is funded and delivered in the U.K. increase the need for
      managers to understand the effects of research activity in their areas. The U.K.
      Clinical Research Facilities Network study intensity tool is a research-specific
      workforce planning tool designed to assess and predict the amount of time and
      staffing required for individual research studies. This article shows how the
      tool can be used by non-research managers, organisations, research nurses and
      allied health professionals to plan, assess and monitor studies, and to maintain
      a value-for-money service.

PMID- 22662582
TI  - Ethics of everyday decision making.
AB  - Evidence suggests that checklists can prevent episodes of patient harm and they
      are increasingly being used in patient care to ensure that procedures are being
      carried out. However, checklists cannot do so alone and in some situations the
      checklist might indicate that an intervention has been undertaken when it has
      not. Healthcare providers, particularly nurses, must consider not only the
      increase in the use of checklists, but also the way in which they present a
      context for ethical decision making. This article examines the ethical dimensions
      of using checklists, played out in the context of a scenario, and suggests that
      failure to take ethics into account when considering checklists might perpetuate
      rather than prevent unsafe practices or errors. The article is set in a US
      context, but the issues are relevant to healthcare settings in any part of the
      world.

PMID- 22662583
TI  - Tailor chemotherapy education and equipment strategies based on risk and
      frequency.

PMID- 22662584
TI  - Chemotherapy administraion in non-oncology settings.

PMID- 22662585
TI  - How do you administer chemotherapy in non-oncology settings at your institution?

PMID- 22662586
TI  - Children's coping strategies for chemotherapy-induced nausea and vomiting.

PMID- 22662587
TI  - The case of the burning back.

PMID- 22662588
TI  - Risk of miscarriage is increased for nurses handling chemotherapy.

PMID- 22662589
TI  - What affects patient adherence to oral chemotherapy?

PMID- 22662590
TI  - Effectiveness of Gambusia holbrooki fish in domestic water containers and
      controlling Aedes aegypti larvae (Linnaeus, 1762) in southwest Saudi Arabia
      (Jeddah).
AB  - The objective of this study was to estimate the survival of Gambusia holbrooki
      (Cyprinodontiformes: Poeciliidae) fishin domestic containers in Jeddah, as well
      as its effectiveness in the control of immature A.aegypti. The use of G.
      holbrooki compared to Bacillus thuringiensis israelensis (B.t.i.)was donein
      domestic containers. In a first home visit, G. holbrooki or B.t.i were applied to
      water containers. Two follow-up visits were conducted after 3-4 & 5-6 months to
      assess the presence of viable fish in the containers and infestation by larvae.
      G. holbrooki fish were still present in 97.6% of containers 45-60 days after
      application. The infestation rate was significantly higher (P < 0.001) in the
      B.t.i group (IR ratio=21.60, 95% CI: 6.46-72.28). In deposits where the fish
      remained, efficacy was 85% better than B.t.i. The permanence of fish was higher
      in concrete tanks (48.5%) located outside the house (47.5%) and at ground level
      (53.3%).

PMID- 22662591
TI  - Monogenean community structure of Oreochromis niloticus in relation to heavy
      metal pollution and host reproductive cycle.
AB  - The community structure of monogenean parasites of Oreochromis niloticus and its
      relation to the variations of heavy metal concentrations in water and the host
      reproductive cycle (gonadosomatic index, GSI) was studied. Fish were collected
      from Fishermen Lake, Ismailia. Monogenea community consisted of seven species,
      Cichlidogyrus halli typicus (57.8%), C. thurstonae (35.3%), C. ergensi (13.8 %),
      C. tiberianus (16.4%), C. arthracanthus (13.8%), Scutogyrus longicornis (22.4%)
      and Gyrodadtylus cicchlidarum (18.9 %). The overall mean species richness per
      host was 4.45 +/- 0.34. Responses of monogenea regarding their prevalence,
      abundance and intensity to the host sex and seasonal variations varied according
      to the species. Monogenean community showed different responses to the heavy
      metal concentrations and GSI. Positive correlations were found between species
      richness and both gonadosomatic index (rs = 0.2, P = 0.03) and Cd concentrations
      (rs = 0.89, P=0.04). Prevalence of C. halli typicus and C. thurstonae showed
      significant negative and positive correlations, respectively with the levels of
      Cu and Pb. G. cicchlidarus showed significant positive correlation with Cd level.
      The abundance and intensity of those species showed also correlations with the
      metal concentrations. Other monogenean species did not show any response to the
      metal levels such as C. tiberianus. Zn did not show any effect on the infection
      parameters of any species of monogenean community. The possibility of using some
      monogenean species to act as indicators for environmental pollution was
      discussed.

PMID- 22662592
TI  - Serum SP-D levels as a biomarker of lung injury in children suffering of
      bronchopneumonia.
AB  - The efficacy of SP-D concentration as a useful biomarker of the severity of lung
      injury in children with bronchopneumonia with or without chronic airway disease
      was studied. A total of 48 patients (2 to 4 years old) diagnosed bronchopneumonia
      were admitted to Department of Pediatrics, Al-Dar hospital, Al-Madinah, Saudi
      Arabia over the year 2009. They were divided into two groups: G1 included
      patients without any underlying disease and G2 included asthmatic patients. They
      were assigned to one of three categories. Stage A patients without oxygen dosage,
      Stage B patients required oxygen dosage, and Stage C patients required ICU
      admission. We evaluated baseline characteristics, clinical features, and serum SP
      D concentration in G1, G2, and G3a (healthy control cross-matched infants). The
      mean serum SP-D concentrations in G1 and G2 were higher than those in G3 (118.7
      +/- 46.2 & 39.7 +/- 18.7 ng/ml, respectively), but also higher in G2 than in G1
      (149.9 +/- 52.8 & 109.8 + 36.7 ng/ml, respectively). The mean serum SP-D
      concentrations were higher in Stage C than in Stages A or B patients, and mean
      serum SP-D concentrations were higher in Stage B than in Stage A.

PMID- 22662593
TI  - Hepatitis C virus infection associated arthritis.
AB  - Hepatitis C-related arthropathy is one of the most common extra hepatic
      manifestations (EHMs) of HCV that may resemble rheumatoid arthritis (RA).
      Although symptoms can be disabling, prognosis typically is benign. The frequency
      and pattern of arthritis associated with chronic HCV patients and differentiation
      from RA was clinically, radiologically and laboratory studied. The study was
      carried out on two groups: GI: 100 patients diagnosed as RA according to the
      American College of Rheumatologist (ACR) and GII 100 chronic HCV patients. All
      patients underwent detailed history and complete general and locomotors
      examination. Complete blood picture (CBC), erythrocyte sedimentation rate (ESR),
      C reactive protein (CRP) and liver functions tests. HCV-RNA was done by HCV
      RNA/RT-PCR. Anti-cyclic citrullinated peptide (Anti-CCP) antibody and rheumatoid
      factor (RF-IgM) was estimated by ELISA. Cryoglobulin were done to all patients.
      Plain X-rays for hands, wrists or knee were obtained on chronic HCV patients who
      had articular involvement at the time of anti-CCP antibody analysis. 17% GII had
      articular manifestations as 76.5% of them were polyarticular, while the remaining
      was monoarticular that associated with cryoglobulinemia. RF-IgM was 79% & 64.7%
      GI and HCV patients with articular manifestation (GII-A) respectively with no
      statistical significance. Anti-CCP was75 % and 11.7% positive of GI and GII-A
      respectively which was statistically significant. Cryoglobulinemia was positive
      in 15 % and 23.5% G1 and GII-A with no statistical significance.

PMID- 22662594
TI  - Aedes aegypti (Linnaeus) re-emerging in southern Egypt.
AB  - Aedes aegypti is one of the demonstrated vector-borne diseases worldwide
      particularly in the Sub-Sahara of Africa. Its re-emergence in the Egyptian
      southern border (Aswan) and now in Toshka is an integration mark. Ae. aegypti
      medical importance, epidemiological implications, ecological behaviors and
      control measures were discussed.

PMID- 22662595
TI  - Combined effect of biopesticides on the digestive enzymatic profiles of Aedes
      aegypti (Diptera: Culicidae).
AB  - This study evaluated efficiency of two bacterial mosquito larvicides and a plant
      extract one against Aedes aegypti larvae when used in combinations with each
      other under laboratory conditions, is an integrated method of control. Plant
      extracts, especially botanical insecticides, are currently studied more and more
      because of the possibility of their use in plant protection. Many of the natural
      plant compounds and organic compounds used in the control of insect pests are
      known to affect digestive enzymes. When fed a diet of rice leaves treated with
      botanical insecticides and bacterial toxins in bioassays, activities of the
      digestive enzymes protease, amylase, and lipase in the A. aegypti larvae are
      affected. Digestive enzyme activities were affected by botanical insecticides and
      bacterial toxins individually and in combination. When combined, the effect was
      more severe at low concentration. There were statistically significant
      differences (P < or = 0.05) in enzyme activities in combined and individual
      treatments. The combination of Btk and botanical insecticides caused a two-fold
      decrease in enzyme activity even at reduced concentration. Clear dose-response
      relationships were established with respect to enzyme activity. A synergistic
      effect of botanical insecticides and bacterial toxins was found when combined in
      low doses. These effects are most pronounced in early instars.

PMID- 22662596
TI  - Hemospermia after transrectal ultrasound (TRUS)-guided prostatic biopsy: a
      prospective study.
AB  - Trans-rectal Ultrasound (TRUS) is a safe, cost-effective, radiation free imaging
      modality for evaluation of prostate. But unfortunately, hemospermia is known to
      be associated with TRUS -guided prostate biopsy. This study measured the
      incidence & risk factors, of hemospermia in patients undergoing trans-rectal
      ultrasonography (TRUS). A prospective observational study involving patients
      undergoing TRUS for suspected prostate cancer has been conducted at Al-Hussein
      and Sayed Galal, University Hospitals. 40patients were included in the study. The
      results showed that 18 out of 40 patients (45%) undergoing TRUS-guided prostatic
      biopsy, who were able to ejaculate, experienced hemospermia, which was associated
      with some degree of anxiety. The mean duration of hemospermia was 4 (+/- 1.4)
      weeks. The number of ejaculations before the complete resolution of hemospermia
      was 6 (+/- 5.6). None of the clinical and pathological factors were significant
      predictors of the duration of hemospermia.

PMID- 22662597
TI  - Tick paralysis: first zoonosis record in Egypt.
AB  - Tick paralysis caused by the secretion of toxin with saliva while taking a blood
      meal is an important veterinary disease, but is rare in humans. Although it has
      certain geographical proclivities, it exists worldwide. Tick paralysis was
      demonstrated for the first time in Egypt among four children living in rural area
      at Giza Governorate. The clinical pictures were confused with rabies; myasthensia
      gravis; botulism; diphtheritic polyneuropathy encountered in rural areas. The
      recovery of tick infesting the four little children and negative clinical and
      laboratory data of all diseases denoted tick paralysis. The encountered ticks
      infesting their animals were Rhipicephalus sanguineus on dogs, Hyalomma
      dromedarii on camels and Hyalomma anatolicum excavatum and Haemaphysalis sp. on
      goats. The case was recognized as first record of tick paralysis in Egypt.

PMID- 22662598
TI  - Clinical application of transient elastography in prediction of portal
      hypertension related complication in patients with chronic liver diseases.
AB  - Liver cirrhosis (LC) is the final evaluative stage of chronic liver diseases with
      dynamic progressive process to multiple complications especially splenomegaly and
      esophageal varices(EV). Efforts have been made to develop non-invasive predictive
      models that may correlate with LC and EV. The role of liver stiffness measurement
      (LSM)- and spleen stiffness measurement (SSM) by transient elastography (TE) in
      the diagnosis of LC and prediction of EV was studied on 90 subjects selected from
      the outpatient clinics of Bakhash Hospitals. They were classified into three
      groups: GI included 10 healthy volunteers as a control group, GII included 20
      chronic hepatitis (CH) patients and GIII included 60 cirrhotic patients. Patients
      in GIII were further subdivided equally into two subgroups A & B according to
      presence or absence of EV. GIII patients were evaluated by gastroscope for
      screening and grading of EV. All groups were subjected to complete blood picture,
      liver and kidney function testes and abdominal ultrasonography as well as LSM
      (right lobe) and SSM by using fibroscan. LS were significantly higher in LC
      patients as compared with CH patients and controls. At a cutoff value of 9.8 kPa,
      sensitivity, specificity, positive predictive values (PPV) and negative
      predictive values (NPV) for LC were 90%, 73%, 55% &78% respectively. At a cutoff
      value of 17.75 kPa (no varices vs. varices at any grade), sensitivity,
      specificity, PPV & NPV for prediction of EV were 92%, 46.2%, 73% & 67.2%
      respectively. LS at cut off values of 14.4 KPa predicted the splenomegaly. SSM at
      50.4 KPa being the best cut-off value for prediction of varices with sensitivity,
      specificity, PPV, NPV & accuracy were 81.2%, 73.2%, 88.7%, 48.8% & 79.4%
      respectively. Combination of LS >17 KPa & SS > 52, predicted EV with 87.6%
      diagnostic accuracy. As regard EV prediction, combination of LSM & SSM had a
      highest diagnostic accuracy than PSR (76.9% vs. 87.6).

PMID- 22662599
TI  - Morphometric analysis of nodules in human onchocerciasis collected in communities
      of the southern Chiapas focus, Mexico.
AB  - Human onchocerciasis is a disease that remains as an important public health
      problem. The morphometric and physical characteristics of 363 Onchocerca volvulus
      nodules collected in the major endemic focus of onchocerciasis in Southern
      Chiapas (Soconusco), was assessed. In the present work we found that treatment
      the morphometry of 363 onchocercal nodules preserved in a 67% glycerol solution
      was determined by measuring the length, width and thick of each nodule with a
      Vernier caliper. The mass was determined with an analytical balance and the
      volume by measuring the water displacement, while the specific gravity was
      calculated by dividing mass over the volume. Statistical analysis was calculated
      for each parameter. The results showed that the nodules were rather longer than
      wider or thicker. Morphometric characteristics were 9.87 +/-3.70 (mean +/-
      standard deviation), 7.52 +/- 2.81, and 4.62 +/-+/- 2.06 mm for length, width and
      thick respectively. In regard to the shape, 62.81% of the nodules showed a
      lenticular shape, while 18.18% were spherical and 19.01% were ovoid. Based on the
      distribution of frequencies of the length, the nodules were classified in three
      groups: the "small" (5.77 +/- 0.73 mm; n = 104, 28.65%), the "medium" group (9.86
      +/- 2.05 mm; n = 203 nodules, 55.92%), and the group of the "big" ones (16.03 +/-
      1.91 mm; n = 56, 15.43%). Moreover, the physical characteristics were: for the
      mass 0.33 +/- 0.24 g, the volume of displaced water was 0.28 +/- 0.26 ml, and the
      specific gravity was 1.10 +/- 0.55 g/ml. The results indicated that most of the
      Mexican Onchocerca nodules have a lenticular shape with average size of 10x7x5
      mm, which is useful in the knowledge of the genus biodiversity and can be taken
      as a parameter in clinical or epidemiological trials, where onchocerciasis
      remains as a public health problem.

PMID- 22662600
TI  - Studies on some metacestodes immunohistochemical response in mice as a model for
      human cysticercosis: I. Role of Th1 and Th2 cytokines in experimental liver
      granuloma of Mesocestoides corti infected mice.
AB  - Intraperitoneal infection of female BALB/C mice with the Mesocestoides corti
      larvae leading to an intense inflammatory response associated with symptoms
      started to appear between 4-5 weeks post-infection. The hepatic changes in the
      process of granuloma formation after intraperitoneal infection with the
      tetrathiredia of M. corti were analyzed. Histopathological changes were observed
      after five days of infection. As a result of this parasitic infection, an
      extensive inflammatory response took place with infiltrating cells first tracking
      the migratory pathway surrounding the parasites. The pathology associated with
      these processes was very destructive for the liver parenchyma. As the infection
      progressed, neutrophils, macrophages, fibroblasts, mast cells and lymphocytes
      were recruited in the tissue. These immune cells started to surround the
      parasites, leading to the formation of granuloma around them. Both Th1 and Th2
      cytokines interact with each other to regulate and modulate the hepatic granuloma
      formation in infected mice.

PMID- 22662601
TI  - Effect of pancreatic biliary reflux as a cofactor in cholecystitis.
AB  - This study assessed the effect of pancreatico-biliary reflux (PBR) as co-factor
      in the process of chronic cholecystitis by measurement of the levels of active
      pancreatic enzyme amylase in gallbladder bile and serum of patients undergoing
      cholecystectomy. Pancreatic Amylase levels in bile from the gallbladder and serum
      were measured during surgery in 68 patients with chronic calcular cholecystitis
      subjected to elective open or laparoscopic cholecystectomy in the National
      Hepatology and Tropical Medicine Research Institution and Theodore Bilharz
      Research Institute. Bile amylase was detected in 64 patients (94.1%) indicating
      pancreatico-biliary reflux. Biliary amylase level ranged from 20-50 IU/L in 42
      patients (61.76%), below 20 IU/l in 14 patients (20.59%), over 50 IU/L in 8
      patients (11.76%) and undetectable in two patients. According to gallbladder bile
      amylase, the incidence of Occult PBR in patients operated upon for chronic
      calcular cholecystitis was 94.1%. The reason should be clarified by further
      research and wider scale study. Routinely investigating biliary amylase in every
      patient having cholecystitis can be a method for early detection of precancerous
      lesions.

PMID- 22662602
TI  - Role of prophylactic antibiotic in elective laparoscopic cholecystectomy.
AB  - This prospective study was conducted to investigate the efficacy of single-dose
      Ceftazidime as a prophylactic antibiotic to prevent surgical site infections in
      low-risk patients undergoing LC. Two hundred patients included in the study were
      randomly divided into two groups (100 each): G1: patients received intravenous
      Ceftazidime within 60 minutes prior to surgery and G2: received intravenous
      placebo (10 ml isotonic sodium chloride 0.9% solution). All patients were invited
      for examination 10, 20 and 30 days post-operatively and any post-operative
      complications were recorded and managed. Preoperatively; there was no significant
      differences existed between the 2 groups regarding sex, age; body mass index and
      ASA score. Also, the duration of LC surgery, incidence of intra-operative
      gallbladder perforations and spill of bile or stones, incidents of intra
      operative bleeding from either cystic artery or gall bladder liver bed and mean
      postoperative hospital stay were found not significantly different between the 2
      groups. Post operatively there was no statistical difference regarding the
      surgical site infection between the two groups.

PMID- 22662603
TI  - The causes of skin lesions in the returning travelers: with special reference to
      Egypt.
AB  - Often people yearn of a greater travel adventure like a year in Africa to get
      away from their routine situations and locations, for a quick vacation or as a
      means of finding one's self, to enjoy new experiences, to learn and experience
      new languages, new food, and new cultures. While most people associate Sub
      Saharan Africa with safaris, there are endless other possibilities for adventure.
      Some African countries have actual entry requirements and won't let you in unless
      you have proof you've been vaccinated against a specific disease. Every African
      country is unique in the quality of its parks and reserves, roads and other
      infrastructure, visitor accommodations and receptivity to tourists. Creating an
      itinerary and arranging travel logistics can intimidate even the most
      enthusiastic tourist. Others travel more nowadays for the better economy and the
      advancements in transportation make it easier to do so. If family members do not
      reside in the same country or are probably working abroad, other family members
      would want to visit them and would do so as frequently as their resources would
      allow. Visiting families and friends in different states or countries are
      probably the most important reasons for taking time off to travel. No doubt,
      travelling to different climates, cultures and environments abroad can expose to
      tropical infectious diseases and health risks. This review dealt with skin
      lesions in the returning travelers.

PMID- 22662604
TI  - Histopathological findings in appendectomy specimens: a retrospective
      clinicopathological analysis.
AB  - The prevalence and clinical features of the various obstructive lesions in
      appendectomy specimens studied pathologically with special emphasis on
      unusualetiological findings were evaluated. The clinic-pathological data of 251
      patients who underwent appendectomies for presumed acute appendicitis from
      January; 2008 to December; 2010; were reviewed retrospectively. Among all
      appendectomies performed, eleven (4.38%) specimens revealed incidental abnormal
      pathological diagnoses: Four cases (1.59%) of Enterobiusvermicularis, Ascaris
      lumbricoides two cases (0.79 %), schistosomiasis eggs in three cases (1.19%), and
      parasitic amebiasis in two cases (0.79%). None suffered tumor in any
      appendectomies specimens. Mean age was lower, perforated and gangrenous
      appendicitis was absent and negative appendectomy rate was higher in patients
      with unusual appendix pathology.

PMID- 22662605
TI  - Cockroaches and flies in mechanical transmission of medical important parasites
      in Khaldyia Village, El-Fayoum, Governorate, Egypt.
AB  - The role of non-blood sucking insects in dissemination of human parasites was
      investigated in Khaldyia Village, Al-Fayoum Governorate over during the summer of
      2011. A total of 278 American cockroach (Periplaneta americana), and 508 house
      flies Musca domestica var. vicina were collected. The insects were collected
      indoors and outdoors. Flies were abundant in defecation areas and around houses.
      The recovered zoonotic parasites identified were cysts of Entamoeba histolytica
      Cryptosporidium parvum and Balantidium coli, and eggs of Ascaris lumbricoides,
      Anchylostoma deodunale, Enterobius vermicularis, and Trichuris trichura as well
      as larvae of Strongyloides stercoralis.

PMID- 22662607
TI  - Studies on some metacestodes immunohistochemical response in mice as a model for
      human cysticercosis: II-THI type immune response in experimental Braintaenia
      crassiceps infected mice.
AB  - Neurocysticercosis is a serious zoonotic diseas, encountered worldwide, caused by
      the larval stage of Taenia solium. Due to the difficulties facing scientists to
      study the biological, histological and immunological effects of these larvae on
      the human brain, other cestodes with more or less similar larvae (Taenia
      crassiceps) were used. In brain infected mice, Th1 predominant cytokines were
      significantly detected.

PMID- 22662606
TI  - Comparative study between laparoscopic and open repair of paraumbilical hernia.
AB  - This randomized prospective study compared the effectiveness of laparoscopic
      paraumbilical hernioplasty to the conventional open technique. Forty patients
      with paraumbilical hernia were randomly categorized into 2 equal groups. GL
      treated by laparoscopic paraumbilical hernioplasty and GO treated by conventional
      (open) umbilical hernioplasty. The mean length of follow up was 36 months. In GL,
      mean operative time was 58.1 +/- 15.5 minutes, in GO, it was 42.2 +/- 10.3
      minutes (p = 0.0005). Postoperative pain score 6 hours after surgery was 2.95 +/-
      1.19 in GL patients as compared to 6.10 +/- 1.74 in GO ones (p < 0.0001). Mean
      hospitalization time was 1.05 +/- 0.224 days in GL versus 1.25 +/- 0.550 days in
      G O (p = 0.14). There was one conversion (5%) to the open repair. Postoperative
      seroma occurred in 2 patients (10%) in GL and 3 patients (15%) in GO. Three
      patients (15%) in G O developed surgical site infection. Hernia recurrence was
      not seen in either 2 Groups. Mean patient satisfaction score for GL patients was
      7.85 +/- 1.27 versus 6.00 +/- 1.69 for GO patients (p = 0.0004). CONCLUSION:
      Compared to open repair, laparoscopic repair is technically feasible, safe and
      effective, with good clinical outcome. It is associated with longer time for
      surgery but reduced postoperative pain, analgesic requirement, complication and
      infection rates with earlier return to normal activities.

PMID- 22662608
TI  - Ecology of the mosquito larvae in urban environments of Cairo Governorate, Egypt.
AB  - Mosquitoes were surveyed over one year period in two localities in Cairo
      representing different levels of urban planning: El-Muqattam (planned) and Abu
      Seir (unplanned). Culex pipiens, Cx. perexiguus, Cx. pusillus, Ochlerotatus
      caspius, Culiseta longiareolata and Anopheles multicolor were the collected
      species at both sites. Mosquitoes were more common in Abu-Seir than in El
      Muqattam, with larvae of the filaria vector Cx. pipiens accounting for 81% and
      52% of recorded individuals at these sites, respectively. Five types of the
      potential breeding habitats were detected of which, the cesspits (El-Muqattam)
      and drainage canals (Abu-Seir) were the most common while springs in El-Muqattam
      and drainage canals in Abu-Seir were the most productive types. Both Cx. pipiens
      and Cx. perexiguus bred year round with peaks of abundance coinciding with higher
      temperatures.

PMID- 22662609
TI  - The aetiology of acute viral hepatitis among some Egyptian youth.
AB  - Sero-diagnosis for HA, B, C & D were determined among acute hepatitis in 99 male
      military recruits, admitted to MOH Fever Hospital. Their ages ranged from 18-25
      years. The results showed that hepatitis A was 1%, hepatitis B was 52%, acute
      hepatitis on HBsAg carrier was 3%, and hepatitis C was 8%. Among acute B 3% had
      anti-delta antibody. Anti-HCV was found in 2/5 of cases with acute hepatitis in
      HBsAg carriers, 4/21 of cases with past exposure of HBV and in 2/18 of cases
      negative for HBV.

PMID- 22662610
TI  - Complete versus selective axillary lymph node dissection in treatment of early
      breast carcinoma.
AB  - Axillary lymph node dissection for staging the axilla in breast carcinoma
      patients is associated with considerable morbidity, such as edema of the arm,
      pain, sensory disturbances, impairment of arm mobility, and shoulder stiffness.
      Selective lymph node biopsy electively removes the palpable lymph node, which
      gets the drainage from the tumor and should therefore be associated with nearly
      zero morbidity. Postoperative morbidity (increase in arm circumference,
      subjective lymphedema, pain, numbness, effect on arm strength and mobility, and
      stiffness) of the operated arm was prospectively compared in 20 breast carcinoma
      patients after axillary lymph node dissection (ALND) and 20 patients following
      Selective lymph node (SLN) biopsy. Patient characteristics were comparable
      between the two groups. Postoperative follow-up was 15.4 months (range, 4-24
      months) in the SLN group and 17.0 months (range, 4-24 months) in the ALND group.
      Following axillary dissection, patients showed a significant increase in upper
      and forearm circumference of the operated arm compared with the SLN patients, as
      well as a significantly higher rate of subjective lymphedema, pain, numbness, and
      motion restriction. Neither difference between groups regarding arm stiffness or
      arm strength, nor did the type of surgery affect daily living.

PMID- 22662611
TI  - Nutrition in pregnancy and pathogenic diseases.
AB  - A woman's nutritional status should be assessed preconception with the goal of
      optimizing maternal, fetal, and infant health. Pregnancy-related dietary changes
      should begin prior to conception, with appropriate modifications across pregnancy
      and during lactation. The Recommended Dietary Allowances (RDAs) are levels of
      nutrients recommended by an expert IOM panel based on extensive evaluation of
      available scientific evidence and mathematically adjusted to meet the needs of
      97% of the population.

PMID- 22662612
TI  - Aedes mosquito in Aswan Governorate, Egypt.
AB  - Mosquitoes play the most serious role in transmission of many zoonotic diseases
      over the world, particularly in the Tropic and Sub-tropic countries. This paper
      surveyed Aswan Governorate for the immature and matures stages of the tiger
      mosquito, Aedes aegypti.

PMID- 22662613
TI  - Studies on two-port laparoscopic cholecystectomy.
AB  - Generally speaking, the laparoscopic cholecystectomy is performed by using three
      or four ports. Two ports laparoscopic cholecystectomy is a rarely performed
      procedure as it demands greater expertise and skills. Benefits of this technique
      are related to the cost this being cost effective with less scar forming as
      compared to the conventional approach of laparoscopic cholecystectomy. A group of
      twenty cases of laparoscopic cholecystectomy was performed by using only two
      ports. All procedures were completed successfully and no extra port or conversion
      to open procedure was indicated. Mean operation time was 60 minutes. No intra and
      postoperative complication occurred. Hospital stay was one day.

PMID- 22662614
TI  - The efficacy of Origanum vulgare on Eimeria tenella.
AB  - Eimeria tenella is one of the most common and pathogenic species of the genus
      Eimeria in the chicken and is associated with many coccidiosis outbreaks and a
      high rate of mortality. Experimentally, Origanum vulgare proved to be an anti
      Eimeria tenella regimen.

PMID- 22662615
TI  - Rights of authorship: Galenism in writing dental history.

PMID- 22662616
TI  - The 1932 report of the American College of Dentists Commission on Journalism:
      commercialism in dental journals.

PMID- 22662617
TI  - Antoni Cieszynski: a pioneering dentist.
AB  - Cieszynrski was a Polish dentist who formulated the rules of isometry
      (Cieszyrnski's isometry) in dental radiology, which enables precise dental X-ray
      pictures that show the true dimensions of teeth. Cieszynski also developed an
      extra-oral technique of anesthetizing the mandibular alveolar nerve, and a
      treatment for trigeminal neuralgia which involved injections of alcohol to the
      Gasser's ganglion. The clinical activity of Antoni Cieszynski included
      periodontal surgery (Cieszynski-Widmann-Neumann's operation) and surgery of
      abscesses and phlegmones of head and neck. He was also a member of numerous
      scientific societies (ADA, ASI, FDI) and a founder of the first Polish dental
      journal Polska Dentystyka (Polish Dentistry). On the 70th anniversary of Doctor
      Antoni Cieszynski's tragic death, the authors recall his outstanding and fruitful
      clinical career.

PMID- 22662618
TI  - In defense of the rights of authorship of some fundamental rules of X-ray
      technique and accessories. 1924.

PMID- 22662619
TI  - The 1790 desecration of John Milton's bones, hair and teeth in a London church.
AB  - John Milton (1608-1674), England's epic poet and a champion of civil and
      religious liberties, has gone down in history as one of the world's greatest
      philosophers, scholars and authors. Although by age 44 he had become totally
      blind, he steadfastly continued to write and eventually composed his poetic
      masterpieces, "Paradise Lost" and "Paradise Regained." In 1674, John Milton died
      of kidney failure at age 66. He was buried in the "chancel under the clerk's
      desk" in the parish church of St. Giles-without-Cripplegate (London). Exhumed 116
      years after his burial, Milton's corpse received "obscene and scandalous
      treatment", as portions of his bones, hair and teeth were removed, examined and
      indiscriminately dispersed to others.

PMID- 22662620
TI  - Galen on dental anatomy and physiology.

PMID- 22662621
TI  - Dental trade cards XXXV. Fast relief for toothaches.

PMID- 22662622
TI  - Dental postcards XLIX. "Hae ye a dram in the hoose?".

PMID- 22662623
TI  - [Neglected zoonosis: new realities in a global world].

PMID- 22662624
TI  - [Diseases transmitted by ticks locally and abroad].
AB  - This article provides a brief overview of some diseases transmitted by ticks.
      These vectors do not transmit only Lyme disease and tickborne-encephalitis, even
      in Switzerland. Several tick-borne diseases cause nonspecific flu-like symptoms.
      Nevertheless sometimes severe, some of these diseases can be treated with
      specific treatments. Repellents, appropriate clothes impregnated with permethrine
      and prompt removal of the tick are effective preventive measures to limit the
      risk of infection. There is an effective vaccine which protects against tick
      borne encephalitis.

PMID- 22662626
TI  - [Forgotten hepatitis: the hepatitis E].
AB  - Hepatitis E is caused by the Hepatitis E Virus (HEV), entericaly transmitted. In
      areas with poor sanitation, HEV is responsible for high endemicity and major
      outbreaks. In countries with high sanitary conditions, HEV is a zoonosis
      responsible for sporadic cases, and is encountered in travellers returning from
      endemic areas. The clinical manifestations are not distinguishable from that
      caused by other causes of acute viral hepatitis. Fulminant hepatitis are
      encountered in 1 to 4% of acute hepatitis E. Remarquably, mortality among
      pregnant women is very high. Diagnosis can be made by serological testing and
      eventually viral detection by PCR. HEV can cause chronic infection in
      immunocompromised patients. There is no specific therapy. There is no vaccine
      currently available.

PMID- 22662625
TI  - [Rickettsial diseases in Switzerland, update for the general practitioner].
AB  - Rickettsial diseases are arthropod-borne zoonosis. They are still misdiagnosed in
      Switzerland. Since development in molecular genetics, number of pathogenic
      species increased dramatically. In recent years, the incidence rise worldwide.
      Climatic conditions and development of tropical travels could explain it. In a
      near future, the Swiss general practitioner may face an increase of cases.
      Clinical presentation is unspecified. The eschar is the key diagnostic element
      but can be easily overlooked. Serology, the indirect immunofluorescence assay is
      the reference method. PCR can give the diagnosis in acute phase. However
      empirical treatment should be prescribed as soon as diagnosis is suspected. No
      vaccine is currently available and use of repellent is still the best way of
      prevention.

PMID- 22662627
TI  - [Echinococcosis: the threat of the urban fox].
AB  - The incidence of alveolar echinococcosis in Switzerland is on the rise, probably
      due to the proliferation of foxes observed between 1980 and 1995 in both urban
      and rural areas. This is nevertheless a rare disease as humans are not a natural
      host for the parasite. Hepatic tumor-like lesions discovered during a workup for
      jaundice or abdominal pain is the most frequent mode of presentation. In the
      presence of typical radiological features (echography, CT-Scan, MRI), diagnostic
      confirmation can be made by serology. If diagnosis remains doubtful, a biopsy of
      the lesion with histopathological examination and PCR is indicated. Curative
      radical surgery is possible in only 25 to 35% of cases. In non-operable cases,
      long standing antiparasitic therapy allows to stop the progression of lesions.

PMID- 22662628
TI  - [Viral fevers from elsewhere].
AB  - Some viruses are transmitted only in specific parts of the world and do not exist
      in Switzerland. However, the increase in intercontinental travels, the tendency
      of travelers to have activities in remote rural areas, the transportation
      (sometimes forbidden) of exotic animals, the climatic warming and the adaptation
      of viruses to new vectors produce an extension of viral diseases towards Northern
      countries. To improve the identification of these infections in travelers, but
      also in European autochthonous populations, it is necessary to know the clinical
      characteristics and the websites announcing the epidemics. Neurological or
      hemorrhagic signs should incite the clinician to suspect a viral hemorrhagic
      fever, diagnosis to be considered if the destination and chronology are
      compatible, strict isolation measures being necessary.

PMID- 22662629
TI  - [Pulmonary diseases among returning travelers].
AB  - Respiratory tract infections are a frequent cause of travelers' health problems.
      Tropical diseases are relatively rare compared to common respiratory infections.
      Nevertheless, due to their potential gravity, they must be systematically
      considered. The differential diagnosis of tropical pathogens is wide. A targeted
      travel history taking into account specific epidemiological, geographical and
      behavioral risk factors helps focusing biological exams to identify the causative
      diagnosis. The chest radiography remains very helpful in this context; however,
      more specific exams, such as serologies are often necessary to reach a final
      diagnosis.

PMID- 22662630
TI  - [Management of childhood malaria in Switzerland].
AB  - Imported malaria is a rare condition in current paediatric practice in
      Switzerland but should be suspected in all febrile children returning from a
      malaria-endemic region. Immediate treatment is essential to decrease the risk of
      complications and mortality. Severity criteria must always be searched for. We
      suggest a diagnostic strategy based on the use of microscopy and rapid antigen
      detection tests. Treatment depends on the Plasmodium species and the severity of
      illness. For uncomplicated malaria, a drug combination that includes an
      artemisinin derivative should be used in priority. Atovaquone/proguanil
      represents an alternative. Chloroquine can be used in most cases of malaria
      caused by another Plasmodium species. Severe malaria must be treated
      intravenously with quinine and soon with artesunate.

PMID- 22662631
TI  - [Low health literacy: barrier to optimal care].
AB  - Health literacy is defined as "the degree to which individuals have the capacity
      to obtain, process, and understand basic health information and services needed
      to make appropriate health decisions." Low health literacy mainly affects certain
      populations at risk limiting access to care, interaction with caregivers and self
      management. If there are screening tests, their routine use is not advisable and
      recommended interventions in practice consist rather to reduce barriers to
      patient-caregiver communication. It is thus important to include not only
      population's health literacy but also communication skills of a health system
      wich tend to become more complex.

PMID- 22662632
TI  - [Complex illness: integrated and holistic management].

PMID- 22662633
TI  - [Practical ECG problems. Torsade de pointes in an elderly patient].

PMID- 22662634
TI  - [Metamorphosis].

PMID- 22662636
TI  - [A new development in the G-spot anatomy].

PMID- 22662635
TI  - [Cerebrovascular accident: an emergency].

PMID- 22662637
TI  - [Psychiatry in the eyes of Anders Behring Breivik].

PMID- 22662638
TI  - [Hierarchy as management].

PMID- 22662639
TI  - Induced sputum: not only for research but also for better patient management in
      asthma and COPD.

PMID- 22662640
TI  - The role of noninvasive methods in assessing airway inflammation and structural
      changes in asthma and COPD.
AB  - AIM: The aim of our study was to assess the role of non-invasive methods in
      assessing airway inflammation and structural changes in asthma and COPD. METHODS:
      The study was conducted on patients attending outpatient and inpatient department
      of TB and Chest Diseases and Department of Pathology at our hospital from January
      2006 to August 2007. 50 asthmatic and 46 COPD patients were selected. A detailed
      history and clinical examination, routine laboratory investigations, pulmonary
      function testing, Chest X-ray PA and lateral view, HRCT Thorax, biochemical and
      cellular analysis of sputum was carried out in all cases. Quality control and
      procedures of pulmomary function test were performed according to the European
      Respiratory Society guidelines. RESULTS: Bronchial wall thickening,
      bronchiectasis and air trapping correlated well with disease severity in
      asthmatics while all abnormal HRCT finding correlate well with disease severity
      in COPD patients. The levels of MMP-9 and TIMP-1 increased significantly with
      increasing disease severity in both asthmatic and COPD groups. The MMP-9/TIMP-1
      ratio decreased with increasing disease severity in both groups. The major source
      of MMP-9 in human lungs is macrophages, neutrophils and eosinophils. Macrophages
      and neutrophils were also the source of TIMP-1. CONCLUSION: Asthma and COPD are
      characterised by an imbalance between MMP-9 and TIMP-1. COPD patients showed a
      higher prevalence of HRCT findings which correlate with their lower MMP-1/TIMP-1
      ratio than asthmatics supporting fact that the destruction and fibrosis of
      alveolar walls are more prominent in COPD. MMP-9/TIMP-1 ratio is associated with
      magnitude of HRCT findings in asthma and COPD and suggests that level of these
      markers reflect the extent of structural changes of airway.

PMID- 22662641
TI  - Volitional assessment of respiratory muscle strength.
AB  - Respiratory muscle weakness may induce dyspnoea, secretion retention and
      respiratory failure. Assessing respiratory muscle strength is mandatory in
      neuromuscular diseases and in case of unexplained dyspnoea. A step by step
      approach is recommended, starting with simple volitional tests. Using spirometry,
      respiratory muscle weakness may be suspected on the basis of an abnormal flow
      volume loop or a fall of supine vital capacity. When normal, maximal inspiratory
      and expiratory pressures against a near complete occlusion exclude significant
      muscle weakness, but low values are more difficult to interpret. Sniff nasal
      inspiratory pressure is a useful alternative because it is easy and it eliminates
      the problem of air leaks around the mouthpiece in patients with neuromuscular
      disorders. The strength available for coughing is easily assessed by measuring
      peak cough flow. In most cases, these simple non invasive tests are sufficient to
      confirm or to eliminate significant respiratory muscle weakness and help the
      timely introduction of ventilatory support or assisted cough techniques. In a
      minority of patients, a more complete evaluation is necessary using non
      volitional tests like cervical magnetic stimulation of phrenic nerves.

PMID- 22662642
TI  - Induced sputum in the management of COPD: clinical implications.
AB  - Sputum induction can be used as a non-invasive technique to investigate airway
      inflammation in asthma and COPD. We reported the case of a 68 year old man with
      COPD, stage III GOLD, that underwent sputum induction during two exacerbation
      episodes. The first cell count showed a typical sputum neutrophilia, whereas the
      second showed sputum eosinophilia. On the basis of sputum cellularity, we decided
      to treat the first episode with a course of antibiotics and the second
      exacerbation with a course of antibiotics and oral steroids. The patient showed
      improvement in both cases, obtaining clinical stabilisation. The induced sputum
      cell count could be a useful technique in a clinical setting to evaluate the
      cellular characteristics of airway inflammation during COPD exacerbation and
      modulate the antinflammatory therapy.

PMID- 22662643
TI  - Combined pulmonary fibrosis and emphysema in a welder.
AB  - Combined pulmonary fibrosis and emphysema (CPFE) syndrome is an uncommon entity
      characterised by emphysema of the upper lobes and diffuse fibrosis of the lower
      lobes and carries a bad prognosis with the onset of pulmonary hypertension. Lung
      involvement due to exposures suffered by welders is generally considered benign
      though, rarely, a diffuse interstitial fibrotic disease has been reported. CPFE
      syndrome has however never been reported in welders. A 65-year-old man, welder by
      occupation and an ex-smoker, presented with progressive exertional dyspnoea
      associated with dry cough noticed for the last four months. On examination, there
      was mild tachypnea, clubbing and bilateral basal velcro crepitations on chest
      auscultation. Lung function test revealed mild mixed ventilatory impairment with
      severe diffusion defect. HRCT chest showed bilateral upper lobe emphysema and
      diffuse interstitial fibrosis in the lower lobes. Transbronchial lung biopsy
      revealed interstitial fibrosis, chronic inflammation and iron deposits. A
      diagnosis of combined pulmonary fibrosis with emphysema (CPFE) with interstitial
      pulmonary siderofibrosis (IPS) was established. A review of literature did not
      show any other report of a similar nature.

PMID- 22662645
TI  - Effusion under the microscope.
AB  - Pseudochylothorax is a very rare form of pleural effusion. It is also called
      chyliform or cholesterol pleural effusion. It is usually a unilateral process and
      approximately one-third of patients are asymptomatic at presentation. We report a
      case of a 60 year old man with a background of rheumatoid arthritis who presented
      with progressive dyspnea. Chest X-ray revealed a new left pleural effusion and a
      small persistent right pleural effusion. He presented 5 years prior due to
      recurrent pleural effusion and no diagnosis was made. Repeat thoracentesis
      yielded 350 milliliters of thick, milky, tan-colored fluid.

PMID- 22662644
TI  - Sarcoidosis and multiple sclerosis: systemic toxicity associated with the use of
      interferon-beta therapy.
AB  - Sarcoidosis is a multi-systemic inflammatory disease of unknown origin
      characterized by the presence of noncaseating epitheloid cell granulomas in
      multiple organs. Diagnosis is made on the basis of a compatible clinical
      radiological scenario and the histological demonstration of the typical
      granulomas in the affected tissues. Interferons are immuno-modulators that have
      been used in a wide range of diseases, including hepatitis C virus infection,
      multiple sclerosis, and multiple myeloma and other types of tumours, including
      leukemia, lymphomas, Kaposi's sarcoma, and melanoma. Interferon-alpha-induced
      sarcoidosis has been reported repeatedly and there are two reports in the
      literature of cases of pulmonary sarcoidosis treated with interferon-1b therapy:
      one for advanced renal cell carcinoma and the other for multiple myeloma. A 35
      year-old man on chronic immune-modulant Interferon-1b-based therapy for multiple
      sclerosis presented to the Neurology Unit with mild dyspnoea, dry cough, and
      transient pain to right upper abdomen. Lungs, spleen, liver, and almost all
      lymphnode stations of abdomen and mediastinum were clearly involved on ultrasound
      examination, chest X-ray, and computed tomography. A transbronchial biopsy showed
      non-caseating granuloma on histopathologic evaluation of the lungs. To the best
      of our knowledge, this is the first report of a chronic multisystemic sarcoidosis
      that was associated with interferon-beta treatment.

PMID- 22662646
TI  - A new type of Hypersensitivity Pneumonitis: salami brusher's disease.
AB  - We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects
      working in a salami factory. The workers had to clean the white mould growing on
      salami surface using a manual wire brush. The five patients (four female) had a
      mean age of 39 +/- 15 years; two were smokers. Three patients had an acute
      clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and
      presented at the emergency department with suspected diagnosis of community
      acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6
      days. Pulmonary function test demonstrated a reduction in diffusing capacity
      (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was
      positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp
      in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3
      subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological
      pattern was a ground glass appearance in the three patients with acute clinical
      onset and a centrilobular one in patients with subacute onset. All patients were
      advised to avoid exposure to the antigens. Follow-up visits including pulmonary
      function testing, and DLCO measurement were conducted at one, three and six
      months. HRCT was performed at six month. Four subjects had a complete
      radiological and clinical resolution after changing work. Only one patient was
      treated with oral steroids for severe dyspnoea and progressive reduction of DLCO,
      gaining a complete radiological and clinical stability at six months.

PMID- 22662647
TI  - Pulmonary sarcoidosis mimicking multiple pulmonary metastases.

PMID- 22662648
TI  - Detection of a possible case of pulmonary tumour thromboembolism by endobronchial
      ultrasound.

PMID- 22662683
TI  - Public outreach.

PMID- 22662684
TI  - Water treatment.

PMID- 22662686
TI  - Software.

PMID- 22662685
TI  - Standards.

PMID- 22662687
TI  - Services.

PMID- 22662688
TI  - Publications.

PMID- 22662690
TI  - professional consulting services directory.

PMID- 22662692
TI  - Dionex corporation.

PMID- 22662693
TI  - J.T. Baker.

PMID- 22662694
TI  - Am.Re services, inc.

PMID- 22662695
TI  - ES&T Information Express.

PMID- 22662697
TI  - International.

PMID- 22662696
TI  - Environment and the white house.

PMID- 22662698
TI  - Federal.

PMID- 22662699
TI  - States.

PMID- 22662700
TI  - Awards.

PMID- 22662702
TI  - Technology.

PMID- 22662701
TI  - Science.

PMID- 22662704
TI  - Measurements.

PMID- 22662703
TI  - Business.

PMID- 22662705
TI  - Clinton pushes alternatively fueled vehicles.

PMID- 22662706
TI  - Flywheel fundamentals.

PMID- 22662707
TI  - Biofuel benefits questioned.

PMID- 22662708
TI  - Shaping environmental in the white house.

PMID- 22662709
TI  - Policy.

PMID- 22662710
TI  - Acs publications.

PMID- 22662711
TI  - Analytical chemistry.

PMID- 22662713
TI  - Acs publications.

PMID- 22662712
TI  - The quest for an advanced regional air quality model.

PMID- 22662714
TI  - Mechanisms white rot fungi use to degrade pollutants.

PMID- 22662715
TI  - Acs publications.

PMID- 22662716
TI  - The SNOX Process: A SUCCESS STORY.

PMID- 22662717
TI  - American chemical society.

PMID- 22662718
TI  - Chemical research in toxicology.

PMID- 22662719
TI  - Eisenreich and the transport of airborne chemicals in aquatic systems.

PMID- 22662720
TI  - Acs publications.

PMID- 22662722
TI  - Acs publications.

PMID- 22662724
TI  - Hazardous waste.

PMID- 22662723
TI  - Acs publications.

PMID- 22662726
TI  - Air pollution.

PMID- 22662725
TI  - Instruments.

PMID- 22662727
TI  - Videoconferencing psychotherapy: a systematic review.
AB  - Individuals with mental health problems may face barriers to accessing effective
      psychotherapies. Videoconferencing technology, which allows audio and video
      information to be shared concurrently across geographical distances, offers an
      alternative that may improve access. We conducted a systematic literature review
      of the use of videoconferencing psychotherapy (VCP), designed to address 10
      specific questions, including therapeutic types/formats that have been
      implemented, the populations with which VCP is being used, the number and types
      of publications related to VCP, and available satisfaction, feasibility, and
      outcome data related to VCP. After electronic searches and reviews of reference
      lists, 821 potential articles were identified, and 65 were selected for
      inclusion. The results indicate that VCP is feasible, has been used in a variety
      of therapeutic formats and with diverse populations, is generally associated with
      good user satisfaction, and is found to have similar clinical outcomes to
      traditional face-to-face psychotherapy. Although the number of articles being
      published on VCP has increased in recent years, there remains a need for
      additional large-scale clinical trials to further assess the efficacy and
      effectiveness of VCP.

PMID- 22662728
TI  - Acceptability and cost-effectiveness of military telehealth mental health
      screening.
AB  - Telehealth has been touted as one solution to the shortage of mental health
      providers within the military. Despite developing evidence for the equivalence of
      telehealth mental health care, there is no research that covers the use of
      telehealth for population mental health screening, a standard component of
      postdeployment medical screening. This paper summarizes soldier perceptions of
      three separate screening events in which telehealth was used and the cost
      effectiveness of telehealth versus in-person implementations of the same
      screening. Soldiers who have not been through telehealth screening report a
      strong preference for in-person screening. Soldiers who have been through
      telehealth screening still report preference for in-person screening, but they
      express more ambivalence about the screening method. Using telehealth-only mental
      health screening for large numbers of soldiers within a compressed time frame is
      more expensive than in-person screening. Telehealth resulted in higher referral
      rates than in-person screening. Government and military leaders should use care
      when making decisions about telehealth implementation. Although telehealth for
      small numbers may be sufficiently equivalent and economical, there is no evidence
      of cost savings or improved acceptability for telehealth mental health post
      deployment screening.

PMID- 22662729
TI  - Telehealth for persons with severe functional disabilities and their caregivers:
      facilitating self-care management in the home setting.
AB  - Persons with severe functional disabilities are the highest users of health care
      services. Caring for the needs of this population represents a significant
      percentage of our national health care costs. A growing body of research has
      demonstrated the efficacy of self-management strategies and caregiver engagement
      for effective long-term care for individuals with chronic medical conditions.
      Economic forces over the past decade have led to new challenges and resulted in
      major changes in health care delivery resulting in shortened length of inpatient
      stays and greater limits on the length of outpatient treatment. Telehealth is an
      innovative method for health care delivery and a means of meeting this new
      challenge. This article highlights the findings of 3 pilot studies on the use of
      telecommunications technologies in promoting self-care management and enhancing
      health care outcomes in persons with severe disabilities and their family
      caregivers. The importance of matching technology to the needs of this
      population, lessons learned from these investigations, and future directions for
      research are addressed.

PMID- 22662730
TI  - A telehealth intervention for veterans on antiviral treatment for the hepatitis C
      virus.
AB  - The standard treatment for chronic hepatitis C (pegylated interferon and
      ribavirin) causes challenging physical and psychological side effects. The
      current pilot study evaluated the efficacy of a brief, telephone-based, cognitive
      behavioral self-management intervention designed to address mood and quality of
      life within a sample of veterans on antiviral treatment for hepatitis C. Results
      from this pilot study support the feasibility of this telehealth intervention,
      showing that veterans were highly satisfied with the content of the intervention
      and compliant with the telephone calls. Findings further indicate that symptoms
      of depression and anxiety and mental health quality of life either remained
      stable or improved in those participants who received the brief telephone
      intervention, while those receiving usual care showed significant declines in
      mood and mental health quality of life. The findings from this study provide
      evidence that a brief, clinician-administered phone intervention may help
      individuals on antiviral therapy for hepatitis C to cope more effectively with
      the negative treatment side effects.

PMID- 22662731
TI  - Interactive voice response for relapse prevention following cognitive-behavioral
      therapy for alcohol use disorders: a pilot study.
AB  - Relapse after alcoholism treatment is high. Alcohol Therapeutic Interactive Voice
      Response (ATIVR) is an automated telephone program for posttreatment self
      monitoring, skills practice, and feedback. This pilot study examined feasibility
      of ATIVR. Participants (n = 21; 57% male) had access to ATIVR for 90 days
      following outpatient group cognitive-behavioral therapy (CBT) to make daily
      reports of mood, confidence in sobriety, urges to use substances, and actual use.
      Reports of relapse or risk were followed with additional questions. Participants
      received personalized therapist feedback based on responses, and could access
      recorded CBT skill reviews. Pre-post assessments included: alcohol consumption
      (Timeline Follow-Back), self-efficacy (Situational Confidence Questionnaire), and
      perceived coping ability (Effectiveness of Coping Behaviors Inventory).
      Participants called on 59% of scheduled days and continued making calls for an
      average of 84 days. Following ATIVR, participants gave feedback that ATIVR was
      easy to use and increased self-awareness. Participants particularly liked the
      therapist feedback component. Abstinence rate increased significantly during
      ATIVR (p = .03), and both self-efficacy and coping significantly improved from
      pre-CBT to post-ATIVR (p < .01). Results indicate ATIVR is feasible and
      acceptable. Its efficacy should be evaluated in a randomized controlled trial.

PMID- 22662732
TI  - Assessing daily fluctuations in posttraumatic stress disorder symptoms and
      substance use with Interactive Voice Response technology: protocol compliance and
      reactions.
AB  - PTSD symptoms and substance use commonly co-occur, but information is limited
      regarding their interplay. We used ecological momentary assessment (EMA) to
      capture fluctuations in PTSD symptoms and drinking within and across days. Fifty
      Iraq and Afghanistan War veterans completed four daily Interactive Voice Response
      (IVR) assessments of PTSD and substance use with cell phones for 28 days. The
      aims of this study were to (1) describe participant compliance and reactions to
      the protocol and (2) identify participant characteristics and protocol reactions
      that predict compliance. Protocol compliance was high, with participants
      completing an average of 96 out of a total of 112 IVR assessments (86%). While
      some participants perceived that the IVR assessments increased their drinking
      (21%) and PTSD symptoms (60%), self-report measures showed significant decreases
      in PTSD symptoms and nonsignificant decreases in drinking over the assessment
      period. Analyses revealed demographic (e.g., older than 24, full-time employment,
      more education), clinical (e.g., less binge drinking, less avoidance symptoms),
      and perceived benefit from participation predicted better protocol compliance.
      Results can guide future research on participant predictors of compliance with
      intensive EMA methods.

PMID- 22662733
TI  - Lessons learned from studies of psychotherapy for posttraumatic stress disorder
      via video teleconferencing.
AB  - This article summarizes two ongoing randomized controlled trials that compare
      individual in-person psychotherapy with psychotherapy provided using video
      teleconferencing for military veterans with posttraumatic stress disorder. We
      describe training methods, populations, technology, challenges, successes, and
      lessons learned so far during the trials.

PMID- 22662734
TI  - Tele-pain management: use of videoconferencing technology in the delivery of an
      integrated cognitive-behavioral and physical therapy group intervention.
AB  - Chronic pain has been recognized as a highly prevalent problem, and
      interdisciplinary treatments have been shown to be effective in the treatment of
      chronic pain. An integrated cognitive-behavioral and physical therapy group
      protocol has been developed and then implemented at remote sites using
      videoconferencing technology to provide pain management for veterans. The
      treatment model is summarized and recommendations are made for addressing
      challenges in implementing this type of treatment via videoconferencing.

PMID- 22662735
TI  - The VA Maryland Health Care System's telemental health program.
AB  - The VA Maryland Health Care System introduced videoconferencing technology to
      provide psychiatry, evidenced-based psychotherapy, case management, and patient
      education at rural clinics where it was difficult to recruit providers.
      Telemental health services enable rural clinics to offer additional services,
      such as case management and patient education. Services have been expanded to
      urban outpatient clinics where a limited number of mental health clinic hours are
      available. This technology expands the availability of mental health providers
      and services, allowing patients to receive services from providers located at
      distant medical centers.

PMID- 22662736
TI  - Uniting veterans across distance through a telephone-based Reminiscence Group
      Therapy intervention.
AB  - This report describes the implementation of a six-session telephone-based
      Reminiscence Group Therapy (RGT) intervention for veterans enrolled in a Home
      Based Primary Care Program (HBPC). HBPC psychologists face challenges not
      routinely encountered in the traditional office setting, and the intervention
      demonstrated the feasibility of conducting semistructured group treatment by
      telephone. Postgroup feedback indicated that the veterans found meaning in shared
      experiences and connection with themselves and others. The RGT intervention
      allowed for efficiency in service delivery while also providing an opportunity
      for veterans to socialize and gain a sense of meaningfulness and identity through
      facilitated recall of past experiences.

PMID- 22662737
TI  - VA Puget Sound Telemental Health Service to rural veterans: a growing program.
AB  - The VA Puget Sound Health Care System Telemental Health program connects veterans
      with psychologists, psychiatrists, and social workers via live clinical video
      teleconferencing. Providers deliver care to veterans in rural Veteran Affairs
      medical centers, community-based outpatient clinics and residences, and thus,
      increase access to specialty mental health care for rural and medically
      underserved veteran communities.

PMID- 22662738
TI  - Web-based, psychosocial treatment for substance use disorders in community
      treatment settings.
AB  - The purpose of this multisite clinical trial was to evaluate the effectiveness of
      a web-based version of the Community Reinforcement Approach, plus motivational
      incentives, within community-based, outpatient substance abuse treatment. This
      ongoing study is being conducted within the National Drug Abuse Treatment
      Clinical Trials Network, funded by the National Institute on Drug Abuse. Midway
      through the enrollment of 500 participants, the study is being implemented in 10
      treatment programs across the United States. Information is provided on design,
      sample, intervention and technology, and preliminary lessons learned.

PMID- 22662739
TI  - The use of Internet technology for psychoeducation and support with dementia
      caregivers.
AB  - A large randomized trial evaluated the benefits of online education, support, and
      self-care promotion for caregivers of persons with dementia. Anecdotal reports
      from participants indicated enjoyment of the materials, convenient access from
      home, and support from professionals and other caregivers. A substantial number
      of screened caregivers experienced obstacles of access, cost, and time regarding
      use of technology. Telephone options are being explored, and future caregiving
      generations are expected to have increased exposure and willingness to use
      computer technology, such as the program described here.

PMID- 22662740
TI  - Telephone-delivered psychotherapy for late-life anxiety.
AB  - A randomized controlled trial (RCT) of telephone-delivered cognitive-behavioral
      therapy (CBT) was compared with usual care for late-life anxiety disorders.
      Client satisfaction, as assessed by the Client Satisfaction Questionnaire, was
      high (M = 27.4, range 8-32), and attrition rates were low (8.3%). Preliminary
      results suggest that participants receiving CBT, compared with usual care,
      experience declines in general anxiety, worry, anxiety sensitivity, and insomnia.

PMID- 22662741
TI  - Improving clinical outcomes in psychiatric care with touch-screen technology.
AB  - Patient-focused research, which uses clinical characteristics to predict
      outcomes, is a field in which information technology has been effectively
      integrated with practice. The present research used touch-screen technology to
      monitor the daily self-report measures of 1,308 consecutive inpatients and day
      patients participating in a 2-week cognitive-behavioral therapy group. Providing
      regular feedback was effective in reducing symptoms for patients at risk of poor
      outcomes (Newnham, Hooke, & Page, 2010b). The use of touch screens in psychiatric
      monitoring encourages a collaborative dialogue between patients and therapists
      and promotes engagement in the process of progress monitoring and treatment
      evaluation.

PMID- 22662742
TI  - Using an online viewing system for Parent-Child Interaction therapy consulting
      with professionals.
AB  - Parent-Child Interaction Therapy (PCIT) training was provided to therapists
      working with parents of children with disruptive behavior problems. Therapists
      uploaded video-recordings of selected sessions using a web-based tool for video
      sharing and review, the Video Analysis Tool (VAT). Trainers utilized the VAT for
      consultation to improve treatment fidelity. Clinical practice benefits include
      the ability to provide targeted, specific feedback to the trainees soon after a
      session and to disseminate PCIT to a larger, global audience.

PMID- 22662743
TI  - Inactivation of aerosolized Bacillus atrophaeus (BG) endospores and MS2 viruses
      by combustion of reactive materials.
AB  - Accidental release of biological agents from a bioweapon facility may contaminate
      large areas, possibly causing disastrous environmental consequences. To address
      this issue, novel halogen-containing reactive materials are being designed with
      the added capability to inactivate viable airborne microorganisms. This study
      determined the efficiency of combustion products of such materials to inactivate
      aerosolized bacteria and viruses. Spores of Bacillus atrophaeus and MS2 viruses
      dispersed in dry air were exposed for subsecond time intervals to hydrocarbon
      flames seeded with different reactive powders so that bioaerosol particles
      interacted with the combustion products in a controlled high-temperature
      environment. The experiments were designed to quantify differences in the
      biocidal effects of different reactive material powders including Al and Mg, a
      B*Ti nanocomposite, an 8Al*MoO(3) nanothermite, and a novel Al*I(2)
      nanocomposite. Compared to pure hydrocarbon flame, powder-seeded flame (with no
      iodine) produced about an order of magnitude greater inactivation of bacterial
      spores. The iodine-containing material increased the spore inactivation by
      additional 2 orders of magnitude. The aerosolized MS2 viruses (generally not as
      stress-resistant as spores) were fully inactivated when exposed to combustion of
      either the iodinated or noniodinated powders. Overall, the study suggests a great
      biocidal potential of combustion products generated by novel iodine-containing
      nanocomposite materials.

PMID- 22662744
TI  - Photocatalytic hydrogen evolution from FeMoS-based biomimetic chalcogels.
AB  - The naturally abundant elements used to catalyze photochemical processes in
      biology have inspired many research efforts into artificial analogues capable of
      proton reduction or water oxidation under solar illumination. Most biomimetic
      systems are isolated molecular units, lacking the protective encapsulation
      afforded by a protein's tertiary structure. As such, advances in biomimetic
      catalysis must also be driven by the controlled integration of molecular
      catalysts into larger superstructures. Here, we present porous chalcogenide
      framework materials that contain biomimetic catalyst groups immobilized in a
      chalcogenide network. The chalcogels are formed via metathesis reaction between
      the clusters [Mo(2)Fe(6)S(8)(SPh)(3)Cl(6)](3-) and [Sn(2)S(6)](4-) in solution,
      yielding an extended, porous framework structure with strong optical absorption,
      high surface area (up to 150 m(2)/g), and excellent aqueous stability. Using
      [Ru(bpy)(3)](2+) as the light-harvesting antenna, the chalcogels are capable of
      photocatalytically producing hydrogen from mixed aqueous solutions and are stable
      under constant illumination over a period of at least 3 weeks. We also present
      improved hydrogen yields in the context of the energy landscape of the
      chalcogels.

PMID- 22662745
TI  - Nanochannel-based single molecule recycling.
AB  - We present a method for measuring the fluorescence from a single molecule
      hundreds of times without surface immobilization. The approach is based on the
      use of electroosmosis to repeatedly drive a single target molecule in a fused
      silica nanochannel through a stationary laser focus. Single molecule fluorescence
      detected during the transit time through the laser focus is used to repeatedly
      reverse the electrical potential controlling the flow direction. Our method does
      not rely on continuous observation and therefore is less susceptible to
      fluorescence blinking than existing fluorescence-based trapping schemes. The
      variation in the turnaround times can be used to measure the diffusion
      coefficient on a single molecule level. We demonstrate the ability to recycle
      both proteins and DNA in nanochannels and show that the procedure can be combined
      with single-pair Forster energy transfer. Nanochannel-based single molecule
      recycling holds promise for studying conformational dynamics on the same single
      molecule in solution and without surface tethering.

PMID- 22662746
TI  - The slow-onset nature of allosteric inhibition in alpha-isopropylmalate synthase
      from Mycobacterium tuberculosis is mediated by a flexible loop.
AB  - The identification of structure-function relationships in allosteric enzymes is
      essential to describing a molecular mechanism for allosteric processes. The
      enzyme alpha-isopropylmalate synthase from Mycobacterium tuberculosis (MtIPMS) is
      subject to slow-onset, allosteric inhibition by l-leucine. Here we report that
      alternate amino acids act as rapid equilibrium noncompetitive inhibitors of
      MtIPMS failing to display biphasic inhibition kinetics. Amino acid substitutions
      on a flexible loop covering the regulatory binding pocket generate enzyme
      variants that have significant affinity for l-leucine but lack biphasic
      inhibition kinetics. Taken together, these results are consistent with the
      flexible loop mediating the slow-onset step of allosteric inhibition.

PMID- 22662747
TI  - Structural spectroscopy and dynamics of inter- and intramolecular H-bonding
      interactions of topotecan, a potent anticancer drug, in organic solvents and in
      aqueous solution.
AB  - We report on the role of H-bonding interactions on the UV-visible absorption and
      emission (steady-state and time-resolved) spectroscopy of topotecan (TPT) in
      solution. In aprotic solvents, a very fast (less than 10 ps) excited-state
      intramolecular proton-transfer reaction occurs in the absorbing enol (E) form to
      give a zwitterion (Z) form, emitting with a large Stokes shift. In protic
      solvents like methanol, the time constant of Z* formation is longer (32 ps) due
      to the participation of solvent molecules in the proton-transfer reaction. In
      aqueous solution at near-neutral pH (6.24), a ground-state equilibrium is
      established between E, cation (C), and Z forms. Direct excitation of E leads to
      Z* through two channels: a very fast one (less than 10 ps) involving an
      intramolecular proton-tranfer and a slower one (680 ps) with the C* intermediate
      formation and reaction. A fast (42 ps) deprotonation of E* to give the excited
      anion (A*) also competes with the photoformation of Z* at the S(1) state. At pH
      =12.15, the A structures are the principal emitting species (tau(A) ~ 0.41 ns),
      showing the largest Stokes shift. In aqueous solutions, we cannot exclude the
      existence of an equilibrium between the lactone and carboxylate forms of TPT,
      whose spectroscopic (absorption and emission spectra) and dynamical behaviors
      should not be very different. Time-resolved emission anisotropy measurements in
      solvents of different viscosities suggest that the rotational relaxation time
      (phi) of TPT is mainly governed by the viscosity of the medium, increasing from
      104 ps (in tetrahydrofuran, THF) to 156 ps (in water) and 338 ps (in dimethyl
      sulfoxide, DMSO). These results give spectroscopic and dynamical information on
      the structures, stability, and dynamics (picosecond to nanosecond time scale) of
      TPT in solution. They provide insights on the role of the intermolecular H
      bonding surrounding medium on the ground- and excited-state structure and
      reaction of TPT. The finding should contribute to a better understanding of the
      relationship between the structures of the drug and its surroundings.

PMID- 22662748
TI  - Tuning the optical properties of mesoporous TiO2 films by nanoscale engineering.
AB  - The optical properties of spin-coated titanium dioxide films have been tuned by
      introducing mesoscale pores into the inorganic matrix. Differently sized pores
      were templated using Pluronic triblock copolymers as surfactants in the sol-gel
      precursor solutions and adjusted by varying the process parameters, such as the
      polymer concentration, annealing temperature, and time. The change in refractive
      index observed for different mesoporous anatase films annealed at 350, 400, or
      450  degrees C directly correlates with changes in the pore size. Additionally,
      the index of refraction is influenced by the film thickness and the density of
      pores within the films. The band gap of these films is blue-shifted, presumably
      due to stress the introduction of pores exerts on the inorganic matrix. This
      study focused on elucidating the effect different templating materials (Pluronic
      F127 and P123) have on the pore size of the final mesoporous titania film and on
      understanding the relation of varying the polymer concentration (taking P123 as
      an example) in the sol-gel solution to the pore density and size in the resultant
      titania film. Titania thin film samples or corresponding titanium dioxide powders
      were characterized by X-ray diffraction, cross-section transmission electron
      microscopy, nitrogen adsorption, ellipsometery, UV/vis spectrometry, and other
      techniques to understand the interplay between mesoporosity and optical
      properties.

PMID- 22662752
TI  - Erratum.

PMID- 22662749
TI  - Intravitreal bevacizumab for a subfoveal myopic choroidal neovascularization in
      the first trimester of pregnancy.
AB  - PURPOSE: To report the clinical course of a highly myopic woman treated by a
      single intravitreal injection of bevacizumab during the first trimester of
      pregnancy. METHODS: Observational case report. A 35-year-old woman affected by
      pathologic myopia complained of blurred vision in her left eye in the fourth week
      of pregnancy. A subfoveal myopic choroidal neovascularization (CNV) was diagnosed
      on the basis of slit-lamp fundus biomicroscopy and fluorescein angiography. After
      discussing the treatment-related risks, she was administered an intravitreal
      injection of bevacizumab in her seventh gestational week. During pregnancy, fetal
      ultrasound and ophthalmic examination were performed monthly. After delivery, the
      mother and infant were followed quarterly for 12 months. RESULTS: The patient had
      an uneventful prenatal course and delivered a healthy full-term infant.
      Significant visual improvement with no documented adverse events related to
      treatment was obtained. CONCLUSIONS: In our experience, a single intravitreal
      bevacizumab injection administered during the first trimester of pregnancy did
      not provoke any complications, and was effective in myopic CNV treatment. Further
      studies are warranted to provide more detailed information about this treatment
      and the related risks in pregnant women.

PMID- 22662754
TI  - Manganese(III) acetate mediated oxidative radical cyclizations. Toward vicinal
      all-carbon quaternary stereocenters.
AB  - Manganese(III) acetate mediated oxidative radical cyclizations have been used to
      synthesize a range of densely functionalized and sterically congested
      cyclopentane-lactones. A number of the resulting lactones contain vicinal all
      carbon quaternary stereocenters adjacent to a tertiary benzylic stereocenter and
      are formed with high levels of stereocontrol.

PMID- 22662755
TI  - Capsaicin induces apoptosis of cisplatin-resistant stomach cancer cells.

PMID- 22662756
TI  - Role of reversible dimerization in reactions of amphoteric aziridine aldehydes.
AB  - Unprotected aziridine aldehydes belong to the amphoteric class of molecules by
      virtue of their dual nucleophilicity/electrophilicity. The dimeric nature of
      these molecules, brought together by a weak and reversible aminal "connection",
      was found to be an important element of reactivity control. We present evidence
      that reversible dimer dissociation is instrumental in aziridine aldehyde
      transformations. We anticipate further developments that will unveil other
      synthetic consequences of remote control of selectivity through forging
      reversible covalent interactions.

PMID- 22662757
TI  - Estimation of the incubation period of invasive aspergillosis by survival models
      in acute myeloid leukemia patients.
AB  - The duration of the incubation of invasive aspergillosis (IA) remains unknown.
      The objective of this investigation was to estimate the time interval between
      aplasia onset and that of IA symptoms in acute myeloid leukemia (AML) patients. A
      single-centre prospective survey (2004-2009) included all patients with AML and
      probable/proven IA. Parametric survival models were fitted to the distribution of
      the time intervals between aplasia onset and IA. Overall, 53 patients had IA
      after aplasia, with the median observed time interval between the two being 15
      days. Based on log-normal distribution, the median estimated IA incubation period
      was 14.6 days (95% CI; 12.8-16.5 days).

PMID- 22662759
TI  - Candidemia outcomes not improved with statin use.
AB  - Candidemia is an important cause of morbidity and mortality. As statins interfere
      with yeast membrane synthesis, we assessed whether use of statins during
      candidemia may cause differences in clinical outcomes. A retrospective review of
      124 candidemia episodes during 2003-2008 in which all-cause and attributable
      mortality, length of stay and level of care were compared for patients who
      received and those who did not receive statins. A total of 124 candidemia events
      were observed involving 14 patients on statins and 110 without statins. Overall
      mortality in candidemia cases was 46%, but only 2% was attributed to candidemia.
      No differences were observed in clinical outcomes for the two groups of patients.
      During the last 2-year period of our study, there were higher rates of candidemia
      caused by non-C. albicans Candida spp., particularly those due to C. glabrata and
      C. parapsilosis. In conclusion, statin use during candidemia did not alter
      mortality, length of stay, or intensive care requirement of our patients, despite
      higher rates of non-C. albicans Candida species isolated during the last 2 years
      of our study.

PMID- 22662760
TI  - The possible mechanism of rhapontigenin influencing antifungal activity on
      Candida albicans.
AB  - Rhapontigenin, an aglycone of rhapontin, was produced by biotransformation and we
      investigated its antifungal activity against Candida albicans, one of the most
      important opportunistic fungal pathogens. Rhapontigenin is found to have, in
      vitro, inhibitory activity with a minimal inhibitory concentration (MIC) value
      against all test isolates of 128-256 MUg/ml. We detected increased reactive
      oxygen species (ROS) levels in yeast cultures treated with rhapontigenin at the
      MIC. Rhapontigenin inhibited DNA, RNA, and protein synthesis, especially RNA
      synthesis, and induced morphological changes and apoptosis of C. albicans. The
      apoptotic effect of rhapontigenin on C. albicans at subinhibitory concentrations
      was higher in the stationary growth phase than in the exponential phase, while
      the opposite results were noted with amphotericin B. The mechanism of antifungal
      activity of rhapontigenin may be associated with the generation of ROS that might
      induce apoptosis and it may also involve the inhibition of ergosterol
      biosynthesis.

PMID- 22662758
TI  - Human genetic susceptibility to Candida infections.
AB  - Infections with Candida spp. have different manifestations in humans, ranging
      from mucosal to bloodstream and deep-seated disseminated infections.
      Immunocompromised patients have increased susceptibility to these types of
      infections, due to reduced capacity to elicit effective innate or adaptive
      immunity. In addition, rare and common genetic variants in the human genome have
      been identified that influence susceptibility to Candida infections. Genetic
      determinants of primary immunodeficiencies leading to chronic mucocutaneous
      candidiasis have been reported, and polymorphisms in genes that are known to be
      involved in anti-Candida host defense are associated with increased
      susceptibility to systemic infection. These findings have greatly increased our
      understanding of pathways important for anti-Candida defense in humans, and
      patterns of prevalence of Candida infections. In addition, these pathways may
      offer novel therapeutic targets for treatment. This review provides an overview
      of the current insights in genetic susceptibility to Candida infections and their
      consequences for the immune response against Candida.

PMID- 22662762
TI  - Bis(imidazolin-2-iminato) rare earth metal complexes: synthesis, structural
      characterization, and catalytic application.
AB  - Reaction of anhydrous rare earth metal halides MCl(3) with 2 equiv of 1,3-bis(2,6
      diisopropylphenyl)imidazolin-2-imine (Im(Dipp)NH) and 2 equiv of
      trimethylsilylmethyl lithium (Me(3)SiCH(2)Li) in THF furnished the complexes
      [(Im(Dipp)N)(2)MCl(THF)(n)] (M = Sc, Y, Lu). The molecular structures of all
      three compounds were established by single-crystal X-ray diffraction analyses.
      The coordination spheres around the pentacoordinate metal atoms are best
      described as trigonal bipyramids. Reaction of YbI(2) with 2 equiv of
      LiCH(2)SiMe(3) and 2 equiv of the imino ligand Im(Dipp)NH in tetrahydrofuran did
      not result in a divalent complex, but instead the Yb(III) complex
      [(Im(Dipp)N)(2)YbI(THF)(2)] was obtained and structurally characterized.
      Treatment of [(Im(Dipp)N)(2)MCl(THF)(n)] with 1 equiv of LiCH(2)SiMe(3) resulted
      in the formation of [(Im(Dipp)N)(2)M(CH(2)SiMe(3))(THF)(n)]. The coordination
      arrangement of these compounds in the solid state at the metal atoms is similar
      to that found for the starting materials, although the introduction of the
      neosilyl ligand induces a significantly greater distortion from the ideal
      trigonal-bipyramidal geometry. [(Im(Dipp)N)(2)Y(CH(2)SiMe(3))(THF)(2)] was used
      as precatalyst in the intramolecular hydroamination/cyclization reaction of
      various terminal aminoalkenes and of one aminoalkyne. The complex showed high
      catalytic activity and selectivity. A comparison with the previously reported
      dialkyl yttrium complex [(Im(Dipp)N)Y(CH(2)SiMe(3))(2)(THF)(3)] showed no clear
      tendency in terms of activity.

PMID- 22662763
TI  - Simultaneous resonance Raman optical activity involving two electronic states.
AB  - In the present work, the first observation of strong resonance Raman optical
      activity (RROA) involving more that one resonant electronic state is reported.
      The chiral transition metal complex bis-(trifluoroacetylcamphorato) copper(II),
      abbreviated Cu(tfc)(2), exhibits both resonance Raman (RR) and RROA spectra with
      laser excitation at 532 nm. Vibrational assignments for this complex were carried
      out by comparing the non-RR spectra of Cu(tfc)(2) excited at 1024 nm to density
      functional theory (DFT) calculations. The theory of the single-electronic-state
      (SES) RROA is extended to the next simplest level of theory involving two
      resonant electronic states (TES) without interstate vibronic coupling as an aide
      to the interpretation of the observed TES-RROA spectra. Based on measured UV-vis
      electronic absorbance spectra and corresponding TD-DFT calculations, the most
      likely two states associated with the RROA spectra are identified.

PMID- 22662765
TI  - A new oxyurid species (Nematoda) collected from a Japanese serow, Capricornis
      crispus (Mammalia: Bovidae), in Japan.
AB  - Skrjabinema kamosika sp. n. (Nematoda: Oxyuridae) is described based on both
      sexes collected from endemic Japanese serows, Capricornis crispus (Mammalia:
      Bovidae), of Wakayama Prefecture, western Honshu Island, and Kochi Prefecture,
      Shikoku Island, Japan. It is readily distinguished from the congeners by having
      tricuspid sub-interlabial projections in males, large triangular lateral lobes of
      the lips that do not reach the mouth rim, and a large length ratio of
      alate/nonalate portions of the tail in females. Close identity in the nucleotide
      arrangement of ITS2 region between the present material and that from C. crispus
      of Iwate Prefecture, northern Honshu Island, suggests wide distribution of S.
      kamosika in Japan. In partial 18S rDNA nucleotide sequence, 0.77% differed from
      that of Skrjabinema sp. from Capra hircus in the United States.

PMID- 22662764
TI  - Maize histone H2B-mCherry: a new fluorescent chromatin marker for somatic and
      meiotic chromosome research.
AB  - Cytological studies of fluorescent proteins are rapidly yielding insights into
      chromatin structure and dynamics. Here we describe the production and cytological
      characterization of new transgenic maize lines expressing a fluorescent histone
      fusion protein, H2B-mCherry. The transgene is expressed under the control of the
      maize ubiquitin1 promoter, including its first exon and intron. Polymerase chain
      reaction-based genotyping and root-tip microscopy showed that most of the lines
      carrying the transgene also expressed it, producing bright uniform staining of
      nuclei. Further, plants showing expression in root tips at the seedling stage
      also showed expression during meiosis, late in the life cycle. Detailed high
      resolution three-dimensional imaging of cells and nuclei from various somatic and
      meiotic cell types showed that H2B-mCherry produced remarkably clear images of
      chromatin and chromosome fiber morphology, as seen in somatic, male meiotic
      prophase, and early microgametophyte cells. H2B-mCherry also yielded distinct
      nucleolus staining and was shown to be compatible with fluorescence in situ
      hybridization. We found several instances where H2B-mCherry was superior to DAPI
      as a generalized chromatin stain. Our study establishes these histone H2B-mCherry
      lines as new biological reagents for visualizing chromatin structure, chromosome
      morphology, and nuclear dynamics in fixed and living cells in a model plant
      genetic system.

PMID- 22662766
TI  - Reevaluating key evidence for the development of rehearsal: phonological
      similarity effects in children are subject to proportional scaling artifacts.
AB  - The size of an individual's phonological similarity effect for visually presented
      material is assumed to reflect his or her ability to recode, and by implication
      rehearse, information in verbal short-term memory. Many studies have shown that
      under these conditions, the size of this effect interacts with age, tending to be
      nonsignificant in children younger than 7 years and leading to the conclusion
      that children of this age do not rehearse. In the present study, the size of the
      phonological similarity effect was assessed in a total of 116 children aged
      between 5 and 9 years, manipulating the modality of both encoding and retrieval
      of the memoranda. Although the interaction between age and the size of the
      phonological similarity effect was replicated with visual presentation and verbal
      recall of material, this interaction was also present in other conditions that do
      not require recoding. In addition, the data from this "classic" condition were
      simulated by a model that assumed that the size of the similarity effect is (a)
      proportional to an individual's recall of dissimilar items and (b) constrained by
      a functional floor to recall of similar items. These findings undermine the
      evidence for a qualitative change in recoding and rehearsal at 7 years and
      question the extent to which rehearsal is necessary to explain the development of
      verbal short-term memory performance.

PMID- 22662767
TI  - The home literacy environment and Latino head start children's emergent literacy
      skills.
AB  - This study examined children's early literacy skills in both English and Spanish
      at entry to preschool to investigate the pattern of association among these
      skills and their families' home language and literacy practices. The participants
      were 392 primarily Latino immigrant (85%) families and their children. Mothers
      completed questionnaires about their families and their home literacy environment
      (HLE), and children's emergent literacy skills were measured in English and
      Spanish at the outset of the preschool year. Project assistants interviewed
      mothers in their homes and tallied the presence of literacy-related materials.
      Results of structural equation modeling showed that the 3 preliteracy skills were
      significantly associated within and across English and Spanish, suggesting the
      possible transfer of these early preliteracy skills across languages. For the
      English language HLE, parents' literacy-related behaviors, sibling-child reading,
      and families' literacy resources were all associated with children's English oral
      language skills, and their English print knowledge was associated with their home
      resources. For the Spanish language HLE, only parents' literacy-related behaviors
      were related to children's Spanish oral language and print knowledge skills.
      There were no significant cross-linguistic relations between any aspect of the
      English HLE and children's Spanish preliteracy skills, whereas parents' literacy
      related behaviors in Spanish were negatively associated with children's English
      oral language and phonological awareness skills. Given the importance of oral
      language and vocabulary in promoting children's literacy, these results indicate
      that parents can support this skill in both languages, but their relative impact
      seems to be within rather across language.

PMID- 22662769
TI  - Depressive moods and marital happiness: within-person synchrony, moderators, and
      meaning.
AB  - Recent studies using within-persons designs conceptually replicate and
      substantively extend prior research that has shown marital distress to be a
      robust risk factor for depression. The present investigation further extends this
      within-persons research tradition by increasing the frequency of assessments and
      by adding new moderators and measures in a sample of both newlywed (n = 24) and
      maritally distressed (n = 31) wives. In both samples, the average within-persons
      association between 21 daily assessments of wives' depressed mood and marital
      happiness approximated previous estimates of analogous effects (overall r = 
      .54). Wives reported worse depressive mood symptoms on days they experienced
      lower marital happiness, even after accounting for time and between-person
      variation in marital happiness. Each participant's within-persons mood and
      marital happiness association was then treated as a dependent variable to be
      predicted from theoretically relevant individual differences. Multilevel modeling
      showed that the negative within-person association between daily depressed mood
      and daily marital happiness was especially strong for women who were relatively
      high in depressive symptoms, who had avoidant attachment styles, and who were
      relatively low in marital adjustment.

PMID- 22662768
TI  - Linking questionnaire reports and observer ratings of young couples' hostility
      and support.
AB  - Past studies have correlated observer ratings with questionnaire self- and
      partner-reports of behaviors in close relationships. However, few studies have
      actually proposed and tested longitudinal models that link observer ratings to
      past behaviors and to questionnaire self- and partner-reports of behaviors during
      an observational task. Using data from a panel of 324 young couples, we
      demonstrate that (a) observer ratings of hostility and support are significantly
      related to couple reports of the same behavior in the relationship two years
      earlier, and (b) respondent and partner questionnaire reports of hostility and
      support during the observational task converge with observer ratings of the same
      behavior even after controlling for earlier self- and partner-reports. These
      findings demonstrate that observer reports based on brief discussion tasks
      reflect the tenor of the relationship over a relatively long period of time. They
      also demonstrate that couple reports of interactions reflect observable behaviors
      beyond that attributed to earlier self- and partner-reports. Consistent with
      previous research, effect sizes are larger for hostility than support but there
      are few differences between men and women.

PMID- 22662773
TI  - Virtual chromoendoscopy as an adjuvant to capsule endoscopy: a step ahead?.

PMID- 22662771
TI  - Mother-child interaction and resilience in children with early developmental
      risk.
AB  - Although prenatal and genetic factors make strong contributions to the emergence
      of intellectual disability (ID), children's early environment may have the
      potential to alter developmental trajectories and to foster resilience in
      children with early risk. The present study examined mother-child interaction and
      the promotion of competence in 50 children with early developmental delays. Three
      related but distinct aspects of mother-child interaction were considered:
      maternal technical scaffolding, maternal positive sensitivity, and mother-child
      dyadic pleasure. Children were classified as exhibiting undifferentiated delays
      at age 3, based upon performance on developmental assessments and the absence of
      known genetic syndromes. Mother-child interaction was assessed at age 4 through
      observational ratings of structured laboratory tasks, and through naturalistic
      home observations. ID was identified at age 5 using the dual criteria of
      clinically significant delays in cognitive functioning and adaptive behavior.
      Maternal technical scaffolding and dyadic pleasure each uniquely predicted
      reduced likelihood of later ID, beyond the contributions of children's early
      developmental level and behavioral functioning. Follow-up analyses suggested that
      mother-child interaction was primarily important to resilience in the area of
      adaptive behavior, with scaffolding and dyadic pleasure differentially associated
      with particular subdomains. Implications for theories of intellectual disability
      and for family-based early intervention and prevention efforts are discussed.

PMID- 22662774
TI  - Virtual chromoendoscopy can be a useful software tool in capsule endoscopy.
AB  - BACKGROUND: capsule endoscopy (CE) has revolutionized the study of small bowel.
      One major drawback of this technique is that we cannot interfere with image
      acquisition process. Therefore, the development of new software tools that could
      modify the images and increase both detection and diagnosis of small-bowel
      lesions would be very useful. The Flexible Spectral Imaging Color Enhancement
      (FICE) that allows for virtual chromoendoscopy is one of these software tools.
      AIMS: to evaluate the reproducibility and diagnostic accuracy of the FICE system
      in CE. METHODS: this prospective study involved 20 patients. First, four
      physicians interpreted 150 static FICE images and the overall agreement between
      them was determined using the Fleiss Kappa Test. Second, two experienced
      gastroenterologists, blinded to each other results, analyzed the complete 20
      video streams. One interpreted conventional capsule videos and the other, the CE
      FICE videos at setting 2. All findings were reported, regardless of their
      clinical value. Non-concordant findings between both interpretations were
      analyzed by a consensus panel of four gastroenterologists who reached a final
      result (positive or negative finding). RESULTS: in the first arm of the study the
      overall concordance between the four gastroenterologists was substantial (0.650).
      In the second arm, the conventional mode identified 75 findings and the CE-FICE
      mode 95. The CE-FICE mode did not miss any lesions identified by the conventional
      mode and allowed the identification of a higher number of angiodysplasias (35 vs
      32), and erosions (41 vs. 24). CONCLUSIONS: there is reproducibility for the
      interpretation of CE-FICE images between different observers experienced in
      conventional CE. The use of virtual chromoendoscopy in CE seems to increase its
      diagnostic accuracy by highlighting small bowel erosions and angiodysplasias that
      weren't identified by the conventional mode.

PMID- 22662772
TI  - Perceived partner support in pregnancy predicts lower maternal and infant
      distress.
AB  - Maternal postpartum emotional distress is quite common and can pose significant
      risk to mothers and infants. The current study investigated mothers'
      relationships with their partners during pregnancy and tested the hypotheses that
      perception of prenatal partner support is a significant predictor of changes in
      maternal emotional distress from midpregnancy to postpartum, and contributes to
      maternal ratings of infant distress to novelty. Using a prospective longitudinal
      design, 272 adult pregnant women were interviewed regarding their partner
      support, relationship satisfaction, and interpersonal security (attachment style
      and willingness to seek out support), and they completed standardized measures of
      prenatal symptoms of depression and anxiety (distress). At 6 to 8 weeks'
      postpartum, mothers reported these symptoms again and completed measures of their
      infants' temperament. Structural equation modeling (SEM) was used to test direct
      and indirect contributions of partner support, relationship satisfaction, and
      interpersonal security to maternal and infant postpartum distress. Mothers who
      perceived stronger social support from their partners midpregnancy had lower
      emotional distress postpartum after controlling for their distress in early
      pregnancy, and their infants were reported to be less distressed in response to
      novelty. Partner support mediated the effects of mothers' interpersonal security
      and relationship satisfaction on maternal and infant outcomes. A high-quality,
      supportive partner relationship during pregnancy may contribute to improved
      maternal and infant well-being postpartum, indicating a potential role for
      partner relationships in mental health interventions, with possible benefits for
      infants as well.

PMID- 22662775
TI  - Carbon dioxide vs. air insufflation in ileo-colonoscopy and in gastroscopy plus
      ileo-colonoscopy: a comparative study.
AB  - INTRODUCTION: insufflation with carbon dioxide (CO2) during endoscopies compared
      to air is associated with a decrease in abdominal discomfort after the
      examination, because CO2 is readily absorbed through the small intestine and
      eliminated by the lungs. AIM: the objective of this randomized clinical trial was
      to assess the effect of CO2 insufflation on pain and abdominal distension after
      an ileo-colonoscopy (I) and after an ileo-colonoscopy plus gastroscopy (I+G).
      MATERIAL AND METHODS: we included a total of 309 patients in the study and all
      endoscopies were performed under sedation with propofol. Two hundred fourteen
      patients underwent an I (132 with CO2 / 82 with air) and 95 underwent an I+G (53
      with CO2 / 42 with air). Abdominal pain was studied at 10, 30 and 120 minutes of
      exploration and abdominal perimeter difference before and after the procedure.
      RESULTS: both in group I and in group I+G, the use of CO2 translated into an
      average of abdominal pain significantly lower (p < 0.05). Similarly, a smaller
      increase in waist circumference was found among group I and group I+G, in
      patients where CO2 was used (p < 0.05). CONCLUSION: the insufflation of CO2
      instead of air during the performance of endoscopy significantly reduces the
      discomfort and abdominal pain after an ileo-colonoscopy and after a gastroscopy +
      ileo-colonoscopy.

PMID- 22662777
TI  - HLA-DQ typing in the diagnostic algorithm of celiac disease.
AB  - OBJECTIVE: celiac disease (CD) is an immune-mediated chronic inflammatory disease
      associated with HLA-DQ2 and DQ8 molecules. We evaluated the role of HLA in the CD
      diagnostic algorithm in order to contribute to the development of practical
      indications for the use of HLA typing. MATERIAL AND METHODS: we selected 317
      subjects typed for DR-DQ genes. CD was present in 123 patients, and 89 were
      included in the study; a control sample of 70 healthy individuals was recruited.
      RESULTS: 64% of patients with CD carried DQ2 heterodimer (alpha5beta2), 13.5%
      carried DQ8 heterodimer without DQ2, 21.4% only showed beta2 chain and 1.1% were
      positive for DQ2 alpha5 chain. The only presence of alpha5 chain did not
      predispose to CD, while DQB1*02 allele resulted more frequent than in other
      reports, pointing out the intrinsic correlation between beta2 chain and CD. In
      the case-control study we observed a progression of increased risk, ranging from
      1:7 for HLA-DQ2 homozygous to 1:85 for DQ8 heterozygous subjects. Overall, 8,6%
      of first degree family members were affected, exclusively in presence of HLA-DQ2,
      -DQ8 or DQB1*02, and CD was significantly more frequent among siblings than
      parents. Finally, considering the different patterns of clinical presentation
      among the HLA-DQ risk classes identified we found no relationship between CD
      clinical presentation and HLA-DQ risk categories. CONCLUSIONS: our results
      strengthen the evidence that HLA-DQ status strongly influences the development of
      CD and demonstrate that knowledge of a patient's HLA-DQ genotype allows to
      establish clinically relevant genetic risk profiles.

PMID- 22662776
TI  - Factors related to survival in hepatocellular carcinoma in the geographic area of
      Sabadell (Catalonia, Spain).
AB  - BACKGROUND: hepatocellular carcinoma (HCC) is a very frequent tumor. Screening
      for the disease is effective, but the prognostic factors are difficult to
      evaluate. OBJECTIVES: 1. To determine epidemiological data and the clinical
      course of HCC in our setting. 2. To compare patient survival according to whether
      screening is performed or not. 3. To evaluate survival prognostic factors.
      PATIENTS AND METHODS: data on the epidemiology and clinical course of patients
      diagnosed with HCC were collected on a prospective basis (January 2004-December
      2006). Two groups were considered according to whether screening had been
      performed (group A) or not (group B). RESULTS: a total of 110 patients were
      diagnosed with HCC (70% males). The most common etiology of cirrhosis was
      hepatitis C (56.1%), and 69% presented mild liver failure (Child-Pugh grade A).
      The median follow-up was 1.8 years. Fifty-one percent had been subjected to
      screening. The diagnosis of HCC was established by imaging techniques in 48.2% of
      the cases, and by histological criteria in 51.8%. The median tumor size was 23 mm
      in group A and 28 mm in group B (p = 0.005). Treatment with curative intent was
      provided in 72% of the cases in group A and in 48% in group B (p = 0.011). The
      median overall survival was 1.99 years -2.67 years in group A and 1.75 years in
      group B (p = 0.05). The multivariate analysis of overall survival showed the type
      of treatment (OR = 2.82 95%CI: 1.3-6.12, p = 0.009) and liver function (OR = 1.71
      95%CI: 1.1-2.68, p = 0.020) to be independent predictors of survival.
      CONCLUSIONS: screening allows the diagnosis of smaller lesions and a higher
      percentage of curative treatments. The degree of liver function and the provision
      of curative treatment are independent predictors of survival.

PMID- 22662778
TI  - Role of tight junctions in hepatitis C virus infection.

PMID- 22662779
TI  - Giant hepatocellular carcinoma.

PMID- 22662780
TI  - Rectal ulcer secondary to a fecal impaction due to pomegranate seed bezoar.

PMID- 22662781
TI  - Pseudomyxoma retroperitonei: report of 2 cases and review of the literature.
AB  - Pseudomyxoma peritonei is a rare clinical condition that is characterized by the
      presence of mucinous ascitis. It is believed to originate predominately from a
      mucinous neoplasm of the appendix including a heterogeneous group of tumours
      ranging from indolentto malignant. It was first described in the late 19th
      century. Pseudomyxoma retroperitonei is extremely rare with only 33 cases having
      been reported since the first description in the middle of the 20th century. We
      report two additional cases of pseudomyxoma retroperitonei and present a review
      of the literature.

PMID- 22662782
TI  - [Whipple's disease].

PMID- 22662783
TI  - Small bowel giant cavernous hemangioma diagnosed by capsule endoscopy.

PMID- 22662784
TI  - Role of contrast-enhanced ultrasound in clinical staging of pancreatic cancer.

PMID- 22662785
TI  - Severe thrombocytopenia in liver transplantation.

PMID- 22662786
TI  - Recurrent hepatotoxicity associated with etanercept and adalimumab but not with
      infliximab in a patient with rheumatoid arthritis.

PMID- 22662788
TI  - Intestinal obstruction secondary to endoscopic capsule retention.

PMID- 22662789
TI  - Serious games for patient safety education.

PMID- 22662790
TI  - Peer mentorship for medical students and junior doctors.

PMID- 22662791
TI  - J.T. Baker.

PMID- 22662792
TI  - Research and EPA: A Call for Reform.

PMID- 22662793
TI  - International.

PMID- 22662794
TI  - Federal.

PMID- 22662795
TI  - Science.

PMID- 22662796
TI  - Awards.

PMID- 22662797
TI  - States.

PMID- 22662798
TI  - Business.

PMID- 22662799
TI  - Measurement.

PMID- 22662800
TI  - Technology.

PMID- 22662802
TI  - Reagent chemicals, eighth edition.

PMID- 22662801
TI  - The natural production of chlorinated compounds.

PMID- 22662803
TI  - The Environmental Impact of CFC Replacements HFCs and HCFCs.

PMID- 22662804
TI  - Acs publications.

PMID- 22662805
TI  - ES&T Information Express.

PMID- 22662806
TI  - Monitoring and Modeling VOCs in Wastewater Facilities.

PMID- 22662807
TI  - Are You spending too much time looking up technical words that can't be found by
      your regular spell-checker?

PMID- 22662809
TI  - Don't miss a single issue, Subscribe Today!

PMID- 22662808
TI  - Developments and applications of field mass spectrometers.

PMID- 22662812
TI  - Classified section.

PMID- 22662811
TI  - Products.

PMID- 22662817
TI  - Fifth Conversation in the Discipline Biomolecular Stereodynamics State University
      of New York at Albany, June 02-06, 1987.

PMID- 22662813
TI  - professional consulting services directory.

PMID- 22662818
TI  - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics.

PMID- 22662864
TI  - Design, synthesis, antiviral activity, and SARs of 14
      aminophenanthroindolizidines.
AB  - Based on our previous structure-activity relationship and antiviral mechanism
      studies, a series of 14-aminophenanthroindolizidines (1a-i, 2, and 3) were
      designed, targeting tobacco mosaic virus (TMV) RNA, and synthesized and
      systematically evaluated for their antiviral activity against TMV. The bioassay
      results showed that most of these compounds exhibited good to excellent in vivo
      anti-TMV activity, of which compounds 1d and 1h displayed significantly higher
      activity than commercial ningnanmycin, and thus emerged as potential inhibitors
      of plant virus. The introduction of amino groups at the 14-position of
      phenanthroindolizidines, which is proposed to interact with arginine residues
      around the TMV RNA, increased anti-TMV activity. 

PMID- 22662865
TI  - Regulation exerted by miRNAs in the promoter and UTR sequences: MDR1/P-gp
      expression as a particular case.
AB  - One of the common forms of multidrug resistance (MDR) is caused by activation of
      the mdr1 (ABCB1) gene, resulting in overexpression of P-glycoprotein (P-gp) and
      conferring cancer cell resistance to a broad range of chemotherapeutics.
      Recently, P-gp-mediated MDR has been associated with aberrant expression of
      microRNAs (miRNAs) in several types of cancer. miRNAs are small noncoding RNAs
      that regulate gene expression in a posttranscriptional manner through partial or
      total hybridization with specific sequences in the 3'-UTR of target mRNAs.
      Interestingly, there are at least two reports that suggest an additional
      regulation by miRNAs at the mdr1 promoter level. Here, we critically analyzed
      some of the miRNAs that regulate P-gp expression at two different levels:
      posttranscriptional and transcriptional. We proposed that the latter may occur
      through two possible scenarios: (1) direct miRNA hybridization with an active
      promoter and (2) triplex structure formation (double-stranded DNA/RNA) stabilized
      by Argonaute 2. Also, we classified transcriptional gene silencing (1) by
      homology, represented by small interfering RNAs directed to viral promoters, and
      (2) by complementarity (Watson-Crick/Hoogsteen base pairing), mediated by miRNAs.
      Transcriptional regulation could represent a new avenue of knowledge applicable
      to the modulation of other genes mediated by these noncoding RNAs.

PMID- 22662866
TI  - Chickpea (Cicer arietinum) and other plant-derived protease inhibitor
      concentrates inhibit breast and prostate cancer cell proliferation in vitro.
AB  - The soybean-derived protease inhibitor, Bowman-Birk inhibitor (BBI), is currently
      showing great promise as a novel cancer chemopreventive agent. In contrast to the
      wealth of research conducted on this compound, the anticancer effects of protease
      inhibitors isolated from other leguminous sources have received limited
      attention. In the current study, 7 protease inhibitor concentrates (PICs) were
      isolated from various leguminous sources (including soybean) and characterized.
      The effects of PICs on the proliferation of breast and prostate cancer cells were
      investigated in vitro. Chickpea PIC significantly inhibited the viability of MDA
      MB-231 breast cancer and PC-3 and LNCaP prostate cancer cells at all
      concentrations tested (25-400 MUg/ml). In addition, kidney bean (200, 400
      MUg/ml), soybean (50, 100 MUg/ml), and mungbean (100, 200 MUg/ml) PICs inhibited
      LNCaP cell viability. These findings suggest that leguminous PICs may possess
      similar anticancer properties to that of soybean BBI and deserve further study as
      possible chemopreventive agents.

PMID- 22662867
TI  - Investigations of the supramolecular structure of individual diphenylalanine nano
      and microtubes by polarized Raman microspectroscopy.
AB  - Polarized Raman microspectroscopy and atomic force microscopy were used to obtain
      quantitative information regarding the molecular structure of individual
      diphenylalanine (FF) nano- and microtubes. The frequencies of the Raman spectral
      bands corresponding to the amide I (1690 cm(-1)) and amide III (1249 cm(-1))
      indicated that the FF-molecules interact by hydrogen bonding at the N-H and not
      at the C?O sites. The calculated mean orientation angles of the principal axes of
      the Raman tensors (PARTs) obtained from the polarized Raman spectral measurements
      were 41 +/- 4 degrees  for the amide I and 59 +/- 5 degrees  for amide III. On
      the basis of the orientation of the PART for the amide I mode, it was found that
      the C?O bond is oriented at an angle of 8 +/- 4 degrees  to the tube axis. These
      values did not vary significantly with the diameter of the tubes (range 400-1700
      nm) and were in agreement with the molecular structure proposed previously for
      larger crystalline specimens.

PMID- 22662868
TI  - Tolerability and pharmacokinetics of intravitreal sirolimus.
AB  - PURPOSE: To evaluate the pharmacokinetics (PK) and tolerability of a proprietary
      sirolimus depot-forming ocular formulation in rabbits and humans after a single
      intravitreal (i.v.t.) injection. METHODS: New Zealand White (NZW) rabbits were
      intravitreally injected in both eyes with an injectable formulation in 5 (3 PK
      and 2 tolerability) studies. The rabbits received up to approximately 220 MUg
      sirolimus per eye. At the desired timing post-injection, the animals were
      euthanized; both eyes were enucleated, frozen, and dissected to separate sclera,
      retina/choroid, and vitreous humor (VH). Whole blood (WB) samples were obtained
      at each time point before euthanasia. In clinical trials, patients received an
      i.v.t. injection of approximately 352 MUg sirolimus. Sirolimus concentrations in
      ocular tissues and WB samples were measured using liquid chromatography/tandem
      mass spectrometry (LC/MS/MS). In both single- and repeat-dose tolerability
      studies, systemic and ocular adverse effects were evaluated. RESULTS: After
      i.v.t. administration, sirolimus formed a depot in the VH. During dissolution,
      concentrations in VH were dose related and exhibited continuous release from the
      depot. This was characterized by a gradient of sirolimus concentration in the
      order of VH > retina/choroid > sclera > WB, and the concentrations were
      maintained for approximately 2 months after the i.v.t. injection. After repeat
      dosing (132 MUg), no drug accumulation was seen in the ocular tissue or
      systemically. In clinical studies, the highest blood levels were <2 ng/mL at day
      2, and half-time (t(1/2)) was 8-9 days. There was no accumulation at day 30 after
      the i.v.t. injection (up to 352 MUg). Safety studies conducted on rabbits
      indicated good local tolerability. Sirolimus-related effects were limited to
      minor incipient cataract findings and mild lenticular changes. In the clinical
      studies where sirolimus was intravitreally administered up to 352 MUg, injections
      were well tolerated. CONCLUSIONS: Sustained i.v.t. delivery was achieved in a
      dose-dependent fashion after the i.v.t. injection of a proprietary sirolimus
      depot-forming ocular formulation. Across the tolerability and safety studies, no
      significant findings were observed for systemic and ocular tolerability. The
      human WB levels were well below the daily trough systemic blood level range
      required for systemic immunosuppression. An i.v.t. injection of sirolimus has a
      PK and safety profile that is favorable for treating inflammatory conditions of
      the eye, such as non-infectious uveitis, and warrants further investigation in
      humans.

PMID- 22662871
TI  - Boroalkyl group migration provides a versatile entry into alpha-aminoboronic acid
      derivatives.
AB  - A reaction exemplifying migration of boron-substituted carbon is described. We
      show that alpha-boroalkyl groups of transient boroalkyl acyl azide intermediates
      readily migrate from carbon to nitrogen. This process allows access to a new
      class of stable molecules, alpha-boryl isocyanates, from alpha-borylcarboxylic
      acid precursors. The methodology facilitates synthesis of a wide range of alpha
      aminoboronic acid derivatives, including alpha,alpha-disubstituted analogues.

PMID- 22662870
TI  - Differential surface deposition of complement proteins on logarithmic and
      stationary phase Leishmania chagasi promastigotes.
AB  - Previous works demonstrated that various species of Leishmania promastigotes
      exhibit differential sensitivity to complement-mediated lysis (CML) during
      development. Upon exposure to normal human serum (NHS), cultures of Leishmania
      chagasi promastigotes recently isolated from infected hamsters (fewer than 5 in
      vitro passages) are CML-sensitive when in the logarithmic growth phase but become
      CML-resistant upon transition to the stationary culture phase. Visualization by
      light and electron microscopy revealed dramatic morphological differences between
      promastigotes from the 2 culture phases following exposure to NHS. Flow
      cytometric analysis demonstrated that surface deposition of the complement
      components C3, C5, and C9 correlated inversely with promastigote CML-resistance.
      The highest levels of complement protein surface accumulation were observed for
      logarithmic phase promastigotes, while stationary phase promastigotes adsorbed
      the least amount of complement proteins. Additionally, fluorescence microscopy
      revealed that C3 and C5 localized in a fairly uniform pattern to the plasma
      membrane of promastigotes from logarithmic phase cultures, while the staining of
      promastigotes from stationary phase cultures was indistinguishable from
      background. By Western blot analysis, high levels of the complement proteins C3,
      C5, and C9 were detected in the total lysates of NHS-exposed logarithmic phase L.
      chagasi promastigotes, relative to NHS-exposed stationary phase promastigotes;
      this finding indicates that the low levels of C3 and C5 seen on the surface of
      stationary phase promastigotes were not due to protein uptake/internalization.
      Together, these data demonstrate the differential deposition of complement
      proteins on the surfaces of logarithmic and stationary phase L. chagasi
      promastigotes. The data support a model wherein stationary phase L. chagasi
      promastigotes resist CML by limiting the deposition of C3 and its derivatives,
      which, in turn, limit surface levels of complement proteins (including C5 and C9)
      that form the lytic membrane attack complex.

PMID- 22662869
TI  - Advanced oxidation protein products activate intrarenal renin-angiotensin system
      via a CD36-mediated, redox-dependent pathway.
AB  - AIMS: Activation of intrarenal renin-angiotensin system (RAS) has a detrimental
      effect on the progression of chronic kidney diseases (CKDs), although the
      regulation of intrarenal RAS remains unclear. The aim of the present study was to
      evaluate the role of advanced oxidation protein products (AOPPs) in intrarenal
      RAS activation. RESULTS: AOPPs upregulated the expression of almost all
      components of RAS and increased activity of angiotensin-converting enzyme in
      cultured proximal tubular epithelial cells. The triggering effect of AOPP-albumin
      was 100-times stronger than that of unmodified albumin. The effect of AOPP
      albumin was mainly mediated by a CD36-dependent, redox-sensitive signaling
      involving activation of protein kinase Calpha, NADPH oxidase, and nuclear factor
      kappaB/activation protein-1. Chronic AOPP-albumin loading in unilateral
      nephrectomy rats resulted in deposition of AOPPs in renal tubular cells
      accompanied with local RAS activation and functional perturbations such as
      increase in urinary albumin excretion. Accumulation of AOPPs was also detected in
      human renal tubular cells and correlated with expression of angiotensin II in
      renal biopsies from 19 patients with IgA nephropathy. INNOVATION AND CONCLUSION:
      This study demonstrated for the first time that AOPPs modified albumin functions
      as a strong trigger of intrarenal RAS via a CD36-mediated, redox-dependent
      pathway. Given the fact that accumulation of AOPPs is prevalent in diabetes and
      CKD, targeting AOPPs could be a strategy for the therapeutic intervention of CKD.
      Antioxid. Redox Signal. 18, 19-35.

PMID- 22662872
TI  - Effect of clathrate hydrate formation and decomposition on NMR parameters in THF
      D2O solution.
AB  - The NMR spin-lattice relaxation time (T(1)), spin-spin relaxation time (T(2)) and
      the diffusion coefficient D were measured for (1)H in a 1:17 mol % solution of
      tetrahydrofuran (THF) in D(2)O. The aim of the work was to clarify some earlier
      points raised regarding the utility of these measurements to convey structural
      information on hydrate formation and reformation. A number of irregularities in
      T(1) and T(2) measurements during hydrate processes reported earlier are
      explained in terms of the presence of interfaces and possible temperature
      gradients. We observe that T(1) and T(2) in solution are exactly the same before
      and after hydrate formation, thus confirming that the solution is isotropic. This
      is inconsistent with the presence of memory effects, at least those that may
      affect the dynamics to which T(1) and T(2) are sensitive. The measurement of the
      diffusion coefficient for a number of hours in the subcooled solution before
      nucleation proved invariant with time, again suggesting that the solution remains
      isotropic without affecting the guest dynamics and diffusion.

PMID- 22662874
TI  - Release of carbon nanotubes from an epoxy-based nanocomposite during an abrasion
      process.
AB  - The abrasion behavior of an epoxy/carbon nanotube (CNT) nanocomposite was
      investigated. An experimental setup has been established to perform abrasion,
      particle measurement, and collection all in one. The abraded particles were
      characterized by particle size distribution and by electron microscopy. The
      abrasion process was carried out with a Taber Abraser, and the released particles
      were collected by a tube for further investigation. The particle size
      distributions were measured with a scanning mobility particle sizer (SMPS) and an
      aerodynamic particle sizer (APS) and revealed four size modes for all measured
      samples. The mode corresponding to the smallest particle sizes of 300-400 nm was
      measured with the SMPS and showed a trend of increasing size with increasing
      nanofiller content. The three measured modes with particle sizes from 0.6 to 2.5
      MUm, measured with the APS, were similar for all samples. The measured particle
      concentrations were between 8000 and 20,000 particles/cm(3) for measurements with
      the SMPS and between 1000 and 3000 particles/cm(3) for measurements with the APS.
      Imaging by transmission electron microscopy (TEM) revealed that free-standing
      individual CNTs and agglomerates were emitted during abrasion.

PMID- 22662875
TI  - CVD graphene as interfacial layer to engineer the organic donor-acceptor
      heterojunction interface properties.
AB  - We demonstrate the use of chemical-vapor-deposited (CVD) graphene as an effective
      indium-tin-oxide (ITO) electrode surface modifier to engineer the organic donor
      acceptor heterojunction interface properties in an inverted organic solar cell
      device configuration. As revealed by in situ near-edge X-ray adsorption fine
      structure measurement, the organic donor-acceptor heterojunction, comprising
      copper-hexadecafluoro-phthalocyanine (F16CuPc) and copper phthalocyanine (CuPc),
      undergoes an obvious orientation transition from a standing configuration
      (molecular pi-plane nearly perpendicular to the substrate surface) on the bare
      ITO electrode to a less standing configuration with the molecular pi-plane
      stacking adopting a large projection along the direction perpendicular to the
      electrode surface on the CVD graphene-modified ITO electrode. Such templated less
      standing configuration of the organic heterojunction could significantly enhance
      the efficiency of charge transport along the direction perpendicular to the
      electrode surface in the planar heterojunction-based devices. Compared with the
      typical standing organic-organic heterojunction on the bare ITO electrode, our in
      situ ultraviolet photoelectron spectroscopy experiments reveal that the
      heterojunction on the CVD graphene modified ITO electrode possesses better
      aligned energy levels with respective electrodes, hence facilitating effective
      charge collection. 

PMID- 22662873
TI  - Release factor one is nonessential in Escherichia coli.
AB  - Recoding a stop codon to an amino acid may afford orthogonal genetic systems for
      biosynthesizing new protein and organism properties. Although reassignment of
      stop codons has been found in extant organisms, a model organism is lacking to
      investigate the reassignment process and to direct code evolution. Complete
      reassignment of a stop codon is precluded by release factors (RFs), which
      recognize stop codons to terminate translation. Here we discovered that RF1 could
      be unconditionally knocked out from various Escherichia coli stains,
      demonstrating that the reportedly essential RF1 is generally dispensable for the
      E. coli species. The apparent essentiality of RF1 was found to be caused by the
      inefficiency of a mutant RF2 in terminating all UAA stop codons; a wild type RF2
      was sufficient for RF1 knockout. The RF1-knockout strains were autonomous and
      unambiguously reassigned UAG to encode natural or unnatural amino acids (Uaas) at
      multiple sites, affording a previously unavailable model for studying code
      evolution and a unique host for exploiting Uaas to evolve new biological
      functions.

PMID- 22662877
TI  - TD-CI simulation of the strong-field ionization of polyenes.
AB  - Ionization of ethylene, butadiene, hexatriene, and octatetraene by short, intense
      laser pulses was simulated using the time-dependent single-excitation
      configuration-interaction (TD-CIS) method and Klamroth's heuristic model for
      ionization (J. Chem. Phys.2009, 131, 114304). The calculations used the 6
      31G(d,p) basis set augmented with up to three sets of diffuse sp functions on
      each heavy atom as well as the 6-311++G(2df,2pd) basis set. The simulations
      employed a seven-cycle cosine pulse (omega = 0.06 au, 760 nm) with intensities up
      to 3.5 * 10(14) W cm(-2) (E(max) = 0.10 au) directed along the vector connecting
      the end carbons of the linear polyenes. TD-CIS simulations for ionization were
      carried out as a function of the escape distance parameter, the field strength,
      the number of states, and the basis set size. With a distance parameter of 1
      bohr, calculations with Klamroth's heuristic model reproduce the expected trend
      that the ionization rate increases as the molecular length increases. While the
      ionization rates are too high at low intensities, the ratios of ionization rates
      for ethylene, butadiene, hexatriene, and octatetraene are in good agreement with
      the ratios obtained from the ADK model. As compared to earlier work on the
      optical response of polyenes to intense laser pulses, ionization using Klamroth's
      model is less sensitive to the number of diffuse functions in the basis set, and
      only a fraction of the total possible CIS states are needed to model the strong
      field ionizations.

PMID- 22662879
TI  - Evaporation of water droplets on "lock-and-key" structures with nanoscale
      features.
AB  - Highly ordered poly(dimethylsiloxane) microbowl arrays (MBAs) and microcap arrays
      (MCAs) with "lock-and-key" properties are successfully fabricated by self
      assembly and electrochemical deposition. The wetting properties and evaporation
      dynamics of water droplets for both cases have been investigated. For the MBAs
      case, the wetting radius of the droplets remains unchanged until the portion of
      the droplet completely dries out at the end of the evaporation process. The
      pinning state extends for more than 99.5% of the total evaporation time, and the
      pinning-shrinking transition is essentially prevented whereas in the case of the
      MCAs the contact radius exhibits distinct stages during evaporation and the
      contact line retreats significantly in the middle of the evaporation process. We
      explain the phenomenon by a qualitative energy balance argument based on the
      different shrinkage types of the nanoscale-folded contact line.

PMID- 22662878
TI  - Imidazo[1,2-a]pyridines susceptible to excited state intramolecular proton
      transfer: one-pot synthesis via an Ortoleva-King reaction.
AB  - A short and efficient route to a broad range of imidazo[1,2-a]pyridines from 2
      aminopyridines and acetophenones is achieved by a tandem, one-pot process
      starting with an Ortoleva-King reaction. Optimal conditions for the first step
      were established after examining various reaction parameters (solvent, reagent
      ratios, and temperature). The conditions identified (1st step, neat, 2.3 equiv of
      2-aminopyridine, 1.20 equiv of I(2), 4 h, 110  degrees C; 2nd step, NaOH(aq), 1
      h, 100  degrees C) resulted in the formation of imidazo[1,2-a]pyridines in 40-60%
      yields. The synthesis is compatible with various functionalities (OH, NMe(2), Br,
      OMe). Products containing a 2-(2'-hydroxyphenyl) substituent undergo excited
      state intramolecular proton transfer (ESIPT) in nonpolar and polar-aprotic
      solvents. Although ESIPT-type emission in nonpolar solvents is weak, the Stokes
      shifts are very high (11000 cm(-1)). The comparison of the properties of six
      ESIPT-capable imidazo[1,2-a]pyridines shows the influence of various substituents
      on emission characteristics. All of them also display strong, solid-state
      emission in blue-green-yellow region. 2-Aryl-imidazo[1,2-a]pyridines not capable
      of ESIPT emit in the blue region, displaying high fluorescence quantum yield.

PMID- 22662882
TI  - Chemical & engineering news.

PMID- 22662880
TI  - Investigating the role of the outer-coordination sphere in [Ni(P(Ph)2N(Ph
      R)2)2]2+ hydrogenase mimics.
AB  - A series of dipeptide substituted nickel complexes with the general formula,
      [Ni(P(Ph)(2)N(NNA-amino acid/ester)(2))(2)](BF(4))(2), have been synthesized and
      characterized (P(2)N(2) = 1,5-diaza-3,7-diphosphacyclooctane, and the dipeptide
      consists of the non-natural amino acid, 3-(4-aminophenyl)propionic acid (NNA),
      coupled to amino acid/esters = glutamic acid, alanine, lysine, and aspartic
      acid). Each of these complexes is an active electrocatalyst for H(2) production.
      The effects of the outer-coordination sphere on the catalytic activity for the
      production of H(2) were investigated; specifically, the impact of sterics, the
      ability of the side chain or backbone to protonate and the pK(a) values of the
      amino acid side chains were studied by varying the amino acids in the dipeptide.
      The catalytic rates of the different dipeptide substituted nickel complexes
      varied by over an order of magnitude. The amino acid derivatives display the
      fastest rates, while esterification of the terminal carboxylic acids and side
      chains resulted in a decrease in the catalytic rate by 50-70%, implicating a
      significant role of protonated sites in the outer-coordination sphere on
      catalytic activity. For both the amino acid and ester derivatives, the complexes
      with the largest substituents display the fastest rates, indicating that
      catalytic activity is not hindered by steric bulk. These studies demonstrate the
      significant contribution that the outer-coordination sphere can have in tuning
      the catalytic activity of small molecule hydrogenase mimics.

PMID- 22662881
TI  - Whole-body retention and distribution of orally administered radiolabelled
      zerovalent iron nanoparticles in mice.
AB  - Zerovalent iron nanoparticles (nZVI) are used for in situ remediation of
      contaminated ground water, raising the possibility that nZVI particles or their
      altered residues could contaminate the ground water. Therefore, it is important
      to study their effects on humans and other organisms in vivo. The objective of
      this study was to assess the whole-body retention and terminal disposition of
      neutron-activated radioactive nZVI administered by oral gavage in mice.
      Radioactivity was primarily eliminated in the faeces within 1 day of
      administration. However, a small amount of iron-derived radioactivity appeared in
      the liver after three repeated daily doses. This prototypic study further
      suggests that neutron activation applied judiciously may be broadly applicable to
      studies of nanoparticles derived from other biologically abundant metals.

PMID- 22662883
TI  - Pros and cons of a full-scale chlorine study.

PMID- 22662884
TI  - International.

PMID- 22662885
TI  - Federal.

PMID- 22662886
TI  - Science.

PMID- 22662888
TI  - Business.

PMID- 22662887
TI  - Technology.

PMID- 22662889
TI  - Measurements.

PMID- 22662890
TI  - EPA should relax rules on cleanup standards and fund research and use of new
      technologies through an "infeasibility fee, " report recommends.

PMID- 22662891
TI  - Who Will Pay To Clean Up Britain's Past?

PMID- 22662892
TI  - Sustainable world trade.

PMID- 22662894
TI  - Restoring contaminated groundwater: an achievable goal ?

PMID- 22662895
TI  - Isotec inc.

PMID- 22662897
TI  - Acs iii publications.

PMID- 22662896
TI  - High-speed GC Analysis of VOCs: Sample Collection and Inlet Systems.

PMID- 22662899
TI  - Concentrations and transformations of hazardous air pollutants.

PMID- 22662898
TI  - ES&T Information Express.

PMID- 22662901
TI  - Throwaway data.

PMID- 22662900
TI  - Acs iii publications.

PMID- 22662903
TI  - American chemical society.

PMID- 22662904
TI  - Products.

PMID- 22662905
TI  - Classified section.

PMID- 22662907
TI  - Termination of sickness benefits or transition to disability pension after
      changes in sickness insurance: a Swedish register study.
AB  - PURPOSE: To assess whether the changes in Swedish sickness insurance in 2008 were
      associated with termination of benefits (TOB) or transition to disability pension
      (DP) for individuals in compensated sick leave of varying duration. Changes were
      (1) introduction of sick-listing guidelines and (2) stricter criteria for
      eligibility to disability pension and sickness cash benefit and time limits for
      the latter. METHODS: The study population consisted of 2 556 211 cases of
      compensated sick leave with onset during 2006-2010 from the Swedish national
      social insurance registers. TOB and DP were analysed with Cox-proportional hazard
      regression. RESULTS: After the introduction of sick-listing guidelines, TOB
      increased for both women [hazard ratio (HR) 1.10] and men (HR 1.07). The
      additional introduction of stricter rules 4 months later were modestly associated
      with TOB (HR: women 1.01, men 0.99) and transition to DP among men decreased with
      stronger associations for spells exceeding 180 days (HR 0.86). For women
      transition to DP surprisingly increased with stricter criteria (HR 1.09),
      although this pattern was reversed in sick leave spells exceeding 1 year (HR
      0.90). CONCLUSIONS: Introducing sick-listing guidelines for different illnesses
      and diseases could have had a considerable impact on TOB. The additional
      introduction of stricter eligibility rules and time limits seem to have
      contributed less to TOB but clearly reduced DP in longer sickness spells.

PMID- 22662908
TI  - Conventional (MG-BR46 Conquista) and transgenic (BRS Valiosa RR) soybeans have no
      mutagenic effects and may protect against induced-DNA damage in vivo.
AB  - In the present study, we evaluated the pesticide and metal concentrations as well
      as the antimutagenic and mutagenic properties of commercial soybeans (Glycine
      max). Male Swiss mice were fed diets containing 1%, 10%, or 20% (w/w) transgenic
      soybeans (BRS Valiosa RR) or parental isogenic conventional soybeans (MG-BR46
      Conquista). Cyclophosphamide (50 mg kg-1 b.w.) was added in a single dose 24 h
      before euthanasia as an induction agent. There was no difference in the
      composition (ash, total fat, protein, moisture, and carbohydrates) of the diets
      containing the same soybean concentration. The results show that the commercially
      available Brazilian soybeans tested are free of organochlorine, organophosphate,
      and carbamate pesticides and contain acceptable heavy metal concentrations. Both
      cyclophosphamide and soybean treatments were not sufficient to cause detectable
      oxidative damage on liver by the levels of malondialdehyde and protein carbonyl.
      The transgenic soybeans are also nonmutagenic and have protective effects against
      DNA damage similar to those of conventional soybeans but to a lesser percentage
      (64%-101% for conventional and 23%-33% for transgenic diets).

PMID- 22662909
TI  - Collagen-based fibrillar multilayer films cross-linked by a natural agent.
AB  - Surface functionalization plays an important role in the design of biomedical
      implants, especially when layer forming cells, such as endothelial or epithelial
      cells, are needed. In this study, we define a novel nanoscale surface coating
      composed of collagen/alginate polyelectrolyte multilayers and cross-linked for
      stability with genipin. This buildup follows an exponential growth regime versus
      the number of deposition cycles with a distinct nanofibrillar structure that is
      not damaged by the cross-linking step. Stability and cell compatibility of the
      cross-linked coatings were studied with human umbilical vein endothelial cells.
      The surface coating can be covered by a monolayer of vascular endothelial cells
      within 5 days. Genipin cross-linking renders the surface more suitable for cell
      attachment and proliferation compared to glutaraldehyde (more conventional cross
      linker) cross-linked surfaces, where cell clumps in dispersed areas were
      observed. In summary, it is possible with the defined system to build fibrillar
      structures with a nanoscale control of film thickness, which would be useful for
      in vivo applications such as inner lining of lumens for vascular and tracheal
      implants.

PMID- 22662910
TI  - Contextual factors influencing U.S. college students' decisions to drink
      responsibly.
AB  - This mixed-methods study qualitatively (n = 13-convenience) explored contextual
      factors influencing decisions to drink responsibly, and quantitatively (n = 729
      random) assessed the prevalence of these factors and whether they varied as a
      function of sex and binge-drinking status. Data were collected in 2007 among
      Texas college students. The constant comparison model was used to analyze the
      qualitative data, while one-way ANOVAs and logistic regression were employed to
      assess the quantitative data. Effect sizes are reported for all significant ANOVA
      interactions. Psychometric properties are supplied for all quantitative scales.
      Implication and limitations are noted, and future research directions discussed.

PMID- 22662912
TI  - Naming game on adaptive weighted networks.
AB  - We examine a naming game on an adaptive weighted network. A weight of connection
      for a given pair of agents depends on their communication success rate and
      determines the probability with which the agents communicate. In some cases,
      depending on the parameters of the model, the preference toward successfully
      communicating agents is essentially negligible and the model behaves similarly to
      the naming game on a complete graph. In particular, it quickly reaches a single
      language state, albeit some details of the dynamics are different from the
      complete-graph version. In some other cases, the preference toward successfully
      communicating agents becomes much more important and the model gets trapped in a
      multi-language regime. In this case gradual coarsening and extinction of
      languages lead to the emergence of a dominant language, albeit with some other
      languages still present. A comparison of distribution of languages in our model
      and in the human population is discussed.

PMID- 22662913
TI  - Excess mutual catalysis is required for effective evolvability.
AB  - It is widely accepted that autocatalysis constitutes a crucial facet of effective
      replication and evolution (e.g., in Eigen's hypercycle model). Other models for
      early evolution (e.g., by Dyson, Ganti, Varela, and Kauffman) invoke catalytic
      networks, where cross-catalysis is more apparent. A key question is how the
      balance between auto- (self-) and cross- (mutual) catalysis shapes the behavior
      of model evolving systems. This is investigated using the graded autocatalysis
      replication domain (GARD) model, previously shown to capture essential features
      of reproduction, mutation, and evolution in compositional molecular assemblies.
      We have performed numerical simulations of an ensemble of GARD networks, each
      with a different set of lognormally distributed catalytic values. We asked what
      is the influence of the catalytic content of such networks on beneficial
      evolution. Importantly, a clear trend was observed, wherein only networks with
      high mutual catalysis propensity (p(mc)) allowed for an augmented diversity of
      composomes, quasi-stationary compositions that exhibit high replication fidelity.
      We have reexamined a recent analysis that showed meager selection in a single
      GARD instance and for a few nonstationary target compositions. In contrast, when
      we focused here on compotypes (clusters of composomes) as targets for selection
      in populations of compositional assemblies, appreciable selection response was
      observed for a large portion of the networks simulated. Further, stronger
      selection response was seen for high p(mc) values. Our simulations thus
      demonstrate that GARD can help analyze important facets of evolving systems, and
      indicate that excess mutual catalysis over self-catalysis is likely to be
      important for the emergence of molecular systems capable of evolutionlike
      behavior.

PMID- 22662911
TI  - Evolution of resistance to quorum quenching in digital organisms.
AB  - Quorum sensing (QS) is a collective behavior whereby actions of individuals
      depend on the density of the surrounding population. Bacteria use QS to trigger
      secretion of digestive enzymes, formation and destruction of biofilms, and, in
      the case of pathogenic organisms, expression of virulence factors that cause
      disease. Investigations of mechanisms that prevent or disrupt QS, referred to as
      quorum quenching, are of interest because they provide a new alternative to
      antibiotics for treating bacterial infections. Traditional antibiotics either
      kill bacteria or inhibit their growth, producing selective pressures that promote
      resistant strains. In contrast, quorum quenching and other so-called anti
      infective strategies focus on altering behavior. In this article we evolve QS in
      populations of digital organisms, a type of self-replicating computer program,
      and investigate the effects of quorum quenching on these populations.
      Specifically, we injected the populations with mutant organisms that were
      impaired in selected ways to disrupt the QS process. The experimental results
      indicate that the rate at which these mutants are introduced into a population
      influences both the evolvability of QS and the persistence of an existing QS
      behavior. Surprisingly, we also observed resistance to quorum quenching.
      Effectively, populations evolved resistance by reaching quorum at lower cell
      densities than did the parent strain. Moreover, the level of resistance was
      highest when the rate of mutant introduction increased over time. These results
      show that digital organisms can serve as a model to study the evolution and
      disruption of QS, potentially informing wet-lab studies aimed at identifying
      targets for anti-infective development.

PMID- 22662914
TI  - Wasps, termites, and waspmites: distinguishing competence from performance in
      collective construction.
AB  - We introduce a distinction between algorithm performance and algorithm competence
      and argue that bio-inspired computing should characterize the former rather than
      the latter. To exemplify this, we explore and extend a bio-inspired algorithm for
      collective construction influenced by paper wasp behavior. Despite its being
      provably general in its competence, we demonstrate limitations on the algorithm's
      performance. We explain these limitations, and extend the algorithm to include
      pheromone-mediated behavior typical of termites. The resulting hybrid waspmite
      algorithm shares the generality of the original wasp algorithm, but exhibits
      improved performance and scalability.

PMID- 22662917
TI  - Palladium-catalyzed oxidative carbonylation of benzylic C-H bonds via nondirected
      C(sp3)-H activation.
AB  - A new strategy for generating benzylpalladium reactive species from toluenes via
      nondirected C(sp(3))-H activation has been developed. This led to construction of
      an efficient Pd-catalyzed reaction protocol for the oxidative carboxylation of
      benzylic C-H bonds to form substituted 2-phenylacetic acid esters and derivatives
      from inexpensive, commercially available starting materials.

PMID- 22662959
TI  - Palliative care for cancer-related lymphedema: a systematic review.
AB  - INTRODUCTION: Cancer-related lymphedema management in palliative care remains a
      challenge for health care professionals. We conducted a systematic review of the
      published literature related to the effectiveness of cancer-related lymphedema
      management in the palliative care setting. METHODS: Eleven major medical
      databases were searched. Manuscripts were selected for articles published from
      January 2004 to October 30, 2011, using search terms for lymphedema and
      palliative care. Eleven articles were selected based on defined eligibility
      criteria for final review and were categorized as lymphedema management in
      palliative care by topic experts. Articles were also rated for quality according
      to the Oncology Nursing Society Putting Evidence into Practice((r))
      classification. RESULTS: Five case studies were identified addressing closed
      controlled subcutaneous drainage; one retrospective study on manual lymphatic
      drainage (MLD); two case studies on compression therapy; and three case studies
      on complete decongestive therapy (CDT). All studies were rated in the category of
      "effectiveness not established" due to study limitations in design and sample
      size. Few studies included objective measures of outcomes, and there were no
      randomized controlled trials. There is a need for larger, well-designed research
      studies to test the effectiveness of management of cancer-related lymphedema in
      palliative care.

PMID- 22662960
TI  - Silver nanoparticle monolayer-to-bilayer transition at the air/water interface as
      studied by the GISAXS technique: application of a new paracrystal model.
AB  - An original diffraction model for the analysis of grazing-incidence small-angle X
      ray scattering (GISAXS) from the nanoparticle Langmuir films was developed. This
      model relies on the concept of the 2D hexagonal paracrystal and employs the
      distorted-wave Born approximation that is relevant for GISAXS measurements at the
      air/water interface when the angle of incidence is close to the critical value.
      The model comprises the cases of the close-packed nanoparticle monolayer and
      bilayer with the AB-type layer stacking. In this way, both the lateral (along the
      interface) and vertical (normal to the interface) correlations of the
      nanoparticle positions can be analyzed. The model was applied to an in situ
      GISAXS study of the formation of a silver nanoparticle Langmuir film during
      compression at the air/water interface in the Langmuir-Blodgett trough. Spherical
      nanoparticles of 5.8 +/- 0.6 nm diameter were employed. Different compression
      stages starting from the submonolayer up to the monolayer collapse via bilayer
      formation were analyzed in terms of the mean lateral interparticle distance,
      degree of paracrystal disorder, interlayer distance, vertical disorder, and layer
      stacking type in the bilayer as well as the ratio between the monolayer and
      bilayer coverage in the final film. The model developed is applicable to any
      nanoparticle Langmuir film formed at the air/liquid interface to extract
      structural parameters on the nanoscale. The particular results obtained have
      direct implications on the preparation of silver plasmonic templates with "hot
      spots" for surface-enhanced Raman scattering.

PMID- 22662961
TI  - Decomposition reaction rate of BCl3-C3H6(propene)-H2 in the gas phase.
AB  - The decomposition reaction rate in the BCl(3)-C(3)H(6)-H(2) gas phase reaction
      system in preparing boron carbides was investigated based on the most favorable
      reaction pathways proposed by Jiang et al. [Theor. Chem. Accs. 2010, 127, 519]
      and Yang et al. [J. Theor. Comput. Chem. 2012, 11, 53]. The rate constants of all
      the elementary reactions were evaluated with the variational transition state
      theory. The vibrational frequencies for the stationary points as well as the
      selected points along the minimum energy paths (MEPs) were calculated with
      density functional theory at the B3PW91/6-311G(d,p) level and the energies were
      refined with the accurate model chemistry method G3(MP2). For the elementary
      reaction associated with a transition state, the MEP was obtained with the
      intrinsic reaction coordinates, while for the elementary reaction without
      transition state, the relaxed potential energy surface scan was employed to
      obtain the MEP. The rate constants were calculated for temperatures within 200
      2000 K and fitted into three-parameter Arrhenius expressions. The reaction rates
      were investigated by using the COMSOL software to solve numerically the coupled
      differential rate equations. The results show that the reactions are, consistent
      with the experiments, appropriate at 1100-1500 K with the reaction time of 30 s
      for 1100 K, 1.5 s for 1200 K, 0.12 s for 1300 K, 0.011 s for 1400 K, or 0.001 s
      for 1500 K, for propene being almost completely consumed. The completely
      dissociated species, boron carbides C(3)B, C(2)B, and CB, have very low
      concentrations, and C(3)B is the main product at higher temperatures, while C(2)B
      is the main product at lower temperatures. For the reaction time 1 s, all these
      concentrations approach into a nearly constant. The maximum value (in mol/m(3))
      is for the highest temperature 1500 K with the orders of -13, -17, and -23 for
      C(3)B, C(2)B, and CB, respectively. It was also found that the logarithm of the
      overall reaction rate and reciprocal temperature have an excellent linear
      relationship within 700-2000 K with a correlation coefficient of 0.99996. This
      corresponds to an apparent activation energy 337.0 kJ/mol, which is comparable
      with the energy barrier 362.6 kJ/mol of the rate control reaction at 0 K but is
      higher than either of the experiments 208.7 kJ/mol or the Gibbs free energy
      barrier 226.2 kJ/mol at 1200 K.

PMID- 22662962
TI  - CuI/DMPAO-catalyzed N-arylation of acyclic secondary amines.
AB  - DMPAO has been found to be a powerful ligand to enable copper-catalyzed coupling
      of aryl halides with aliphatic acyclic secondary amines take place under
      relatively mild conditions, and coupling of aryl halides with primary amines and
      cyclic secondary amines proceeds at low catalyst loading.

PMID- 22662963
TI  - An animal model of necrotizing enterocolitis (NEC) in preterm rabbits.
AB  - Creation of an animal model of necrotizing enterocolitis (NEC) allowing
      adjustment of severity and potential recoverability is needed to study
      effectiveness of prevention and treatment strategies. This study describes a
      novel model in preterm rabbits capable of adjusting severity of NEC-like
      histologic changes. Rabbit pups (n = 151) were delivered by cesarean section 2
      days preterm. In the treatment groups, tissue adhesive was applied to anal
      openings to simulate the poor intestinal function and dysmotility of preterm
      neonates. Pups were placed into five groups: 3INT (3 day intermittent block),
      4INT (4 day intermittent block), 3COM (3 day complete block), 4COM (4 day
      complete block), based on differences in type of anal blockage and day of life
      sacrificed. The fifth group, 4CON, was comprised of a control arm (n = 28)
      without anal block, with sacrifice of subjects on day 4. All pups were gavage fed
      with formula contaminated with Enterobacter cloacae, ranitidine, and
      indomethacin. Following sacrifice, the intestines were harvested for pathologic
      evidence of NEC. A blinded pathologist graded histologic changes consistent with
      NEC using a grading scale 0-4 with 4 being most severe. Fifty-seven pups (57/123)
      (46%) in the research arm survived to sacrifice, compared to 26/28 (93%) in the
      control arm of the investigation, p < 0.0001. The incidence and severity of NEC
      like damage increased with the duration and completeness of the anal blockage.
      44/57 (77%) of survivors revealed various degrees of NEC-like damage to large and
      small bowel, and 3/26 (12%) exhibited early NEC-like mucosal injury in the
      research and control arms, respectively. This animal model produces NEC-like
      pathologic changes in both small and large intestine in preterm rabbits. Because
      incidence and severity of damage increases with duration and completeness of
      intestinal dysmotility, this allows future effectiveness studies for nonsurgical
      treatment and prevention of NEC.

PMID- 22662964
TI  - Condensation of a nickel tetranuclear cubane into a heptanuclear single-molecule
      magnet.
AB  - A tetranuclear complex, [Ni(4)], with a cubane-like structure synthesized from
      hexafluoroacetylacetone gives, after drying at high temperature and treatment
      with pyridine, a heptanuclear nickel(II) complex, [Ni(7)]. The crystal structures
      of both compounds have been determined by single-crystal X-ray diffraction. Their
      magnetic properties have been studied by SQUID and MU-SQUID magnetometry as well
      as by high-frequency EPR spectroscopy (HF-EPR). For [Ni(4)], the temperature
      dependence of the magnetic susceptibility can be fitted by taking into account
      strong Ni...Ni ferromagnetic interactions which lead to an S = 4 ground-state
      spin, in good agreement with the HF-EPR study. For [Ni(7)], the temperature
      dependence of the magnetic susceptibility shows that the Ni...Ni ferromagnetic
      interactions are kept within the metal core. However, it was not possible to fit
      this with a clear set of parameters, and the ground-state spin was undetermined.
      The field dependence of the magnetization indicates an S = 7 ground-state spin at
      high field. In contrast, the temperature dependence of the magnetic
      susceptibility indicates a ground-state spin of S = 6 or even S = 5. These
      results agree with complicated high-frequency EPR spectra which have been
      ascribed to the superposition of signals from the ground spin multiplet and from
      an excited spin multiplet very close in energy, with the excited state having a
      larger S value than the ground state. Very low temperature studies show that only
      the heptanuclear complex behaves as a single-molecule magnet.

PMID- 22662965
TI  - Direct chemical method for preparing 2,3-epoxyamides using sodium chlorite.
AB  - A direct method for preparing 2,3-epoxyamides from tertiary allylamines via a
      tandem C-H oxidation/double bond epoxidation using sodium chlorite is reported.
      Apparently, the reaction course consists of two steps: (i) allylic oxidation of
      the starting allylamine to corresponding unsaturated allylamide with sodium
      chlorite followed by (ii) epoxidation of the allylamide to the 2,3-epoxyamide
      mediated by hypochlorite ion, which is formed in situ by reduction of sodium
      chlorite. The reaction conditions tolerate the presence of free hydroxyl groups
      and typical functional groups such as TBS, aryl, alkyl, allyl, acetyl, and benzyl
      groups; however, when an activated aromatic ring (e.g., sesamol) is present in
      the substrate, the use of a scavenger is necessary.

PMID- 22662966
TI  - Cross-cultural application of the Korean version of Ureteral Stent Symptoms
      Questionnaire.
AB  - PURPOSE: We validated the Korean version of the Ureteral Stent Symptoms
      Questionnaire (USSQ) in patients with an indwelling ureteral stent. MATERIALS AND
      METHODS: Linguistic validation of the original USSQ was performed through a
      standard process including translation, back translation, and pilot study. A
      total of 65 patients who underwent ureteroscopic surgery were asked to complete
      the Korean USSQ as well as EuroQOL (male and female), the International Prostate
      Symptom Score (male), and Urogenital Distress Inventory-6 (female). Patients were
      evaluated at weeks 1 and 2 after stent placement and at week 4 after removal.
      Sixty-four healthy subjects without a ureteral stent were also asked to complete
      the Korean USSQ once. The psychometric properties of the questionnaire were
      analyzed. RESULTS: Internal consistencies (Cronbach alpha coefficients: 0.73
      0.83) and test-retest reliability (Spearman correlation coefficient: >=0.6) were
      satisfactory for urinary symptom, body pain, general health, and work performance
      domains. Most USSQ domains showed moderate correlations with each other.
      Convergent validity determined by correlation between other instruments and
      corresponding USSQ domain was satisfactory. Sensitivity to change and
      discriminant validity were also good in most domains (P<0.01). Only a small
      proportion of the study population had an active sexual life, with the stent in
      situ, limiting its analysis. CONCLUSIONS: The Korean version of the USSQ is a
      reliable and valid instrument that can be self-administered by Korean patients
      with a ureteral stent in the clinical and research settings. Further clinical
      studies in the Korean settings would be useful to provide robust data on
      sensitivity to change.

PMID- 22662967
TI  - Targeted metabolomics reveals a male pheromone and sex-specific ascaroside
      biosynthesis in Caenorhabditis elegans.
AB  - In the model organism Caenorhabditis elegans, a class of small molecule signals
      called ascarosides regulate development, mating, and social behaviors. Ascaroside
      production has been studied in the predominant sex, the hermaphrodite, but not in
      males, which account for less than 1% of wild-type worms grown under typical
      laboratory conditions. Using HPLC-MS-based targeted metabolomics, we show that
      males also produce ascarosides and that their ascaroside profile differs markedly
      from that of hermaphrodites. Whereas hermaphrodite ascaroside profiles are
      dominated by ascr#3, containing an alpha,beta-unsaturated fatty acid, males
      predominantly produce the corresponding dihydro-derivative ascr#10. This small
      structural modification profoundly affects signaling properties: hermaphrodites
      are retained by attomole-amounts of male-produced ascr#10, whereas hermaphrodite
      produced ascr#3 repels hermaphrodites and attracts males. Male production of
      ascr#10 is population density-dependent, indicating sensory regulation of
      ascaroside biosynthesis. Analysis of gene expression data supports a model in
      which sex-specific regulation of peroxisomal beta-oxidation produces functionally
      different ascaroside profiles.

PMID- 22662968
TI  - Production of isotopically labeled standards from a uniformly labeled precursor
      for quantitative volatile metabolomic studies.
AB  - Optimal accuracy and precision in small-molecule profiling by mass spectrometry
      generally requires isotopically labeled standards chemically representative of
      all compounds of interest. However, preparation of mixed standards from
      commercially available pure compounds is often prohibitively expensive and time
      consuming, and many labeled compounds are not available in pure form. We used a
      single-prototype uniformly labeled [U-(13)C]compound to generate [U-(13)C]
      labeled volatile standards for use in subsequent experimental profiling studies.
      [U-(13)C]-alpha-Linolenic acid (18:3n-3, ALA) was thermally oxidized to produce
      labeled lipid degradation volatiles which were subsequently characterized
      qualitatively and quantitatively. Twenty-five [U-(13)C]-labeled volatiles were
      identified by headspace solid-phase microextraction-gas chromatography/time-of
      flight mass spectrometry (HS-SPME-GC/TOF-MS) by comparison of spectra with
      unlabeled volatiles. Labeled volatiles were quantified by a reverse isotope
      dilution procedure. Using the [U-(13)C]-labeled standards, limits of detection
      comparable to or better than those of previous HS-SPME reports were achieved,
      0.010-1.04 ng/g. The performance of the [U-(13)C]-labeled volatile standards was
      evaluated using a commodity soybean oil (CSO) oxidized at 60  degrees C from 0 to
      15 d. Relative responses of n-decane, an unlabeled internal standard otherwise
      absent from the mixture, and [U-(13)C]-labeled oxidation products changed by up
      to 8-fold as the CSO matrix was oxidized, demonstrating that reliance on a single
      standard in volatile profiling studies yields inaccurate results due to changing
      matrix effects. The [U-(13)C]-labeled standard mixture was used to quantify 25
      volatiles in oxidized CSO and low-ALA soybean oil with an average relative
      standard deviation of 8.5%. Extension of this approach to other labeled
      substrates, e.g., [U-(13)C]-labeled sugars and amino acids, for profiling studies
      should be feasible and can dramatically improve quantitative results compared to
      use of a single standard.

PMID- 22662970
TI  - Perspective on neuromuscular factors in poststroke fatigue.
AB  - PURPOSE: To summarize the potential origins of fatigue poststroke from a
      neuromuscular perspective, including stroke-induced alterations at the cortical,
      spinal and muscle levels. METHOD: Perspective based on narrative literature
      review. RESULTS: Fatigue is a highly prevalent, but poorly understood symptom
      poststroke. Neuromuscular fatigue has central and peripheral origins. Individuals
      with stroke experienced greater central fatigue and less peripheral fatigue
      during voluntary contractions of the paretic leg in comparison to healthy
      participants. Neuromuscular adaptations to stroke create an increased
      susceptibility to central fatigue, which may be a contributing factor to the
      increased perception of tiredness during performance of activities of daily
      living. Future studies should investigate whether intervention-induced cortical
      plasticity, gains in muscle strength and endurance will attenuate self-reported
      fatigability. CONCLUSIONS: Fatigue is a common and debilitating consequence of
      stroke. Neuromuscular fatigue of central origin may contribute to self-reported
      fatigue. Continued focused and properly designed research studies should provide
      substantial insight into the therapeutic interventions that will improve the
      management of fatigue poststroke.

PMID- 22662969
TI  - Electrophoretic nanotechnology of composite electrodes for electrochemical
      supercapacitors.
AB  - The electrophoretic deposition (EPD) method has been developed for the
      fabrication of MnO(2)-multiwalled carbon nanotube (MWCNT) films for application
      in electrochemical supercapacitors (ESs). For MWCNT applications, which depend on
      electrical conductivity, it is challenging to achieve dispersion and EPD of
      pristine MWCNT and avoid defects due to chemical treatment or functionalization.
      An important finding was the possibility of efficient dispersion and controlled
      EPD of MWCNT using calconcarboxylic acid (CCA). Moreover, the use of CCA allowed
      efficient dispersion of MnO(2) in concentrated suspensions and EPD of MnO(2)
      films. The comparison of the experimental data for chromotrope FB (CFB) and CCA
      and chemical structures of the molecules provided insight into the mechanism of
      CCA adsorption on MnO(2). The fabrication of stable suspensions of MnO(2)
      nanoparticles containing MWCNT, and controlled codeposition of both materials is
      a crucial aspect in the EPD of composites. The new approach was based on the use
      of CCA as a charging and dispersing agent for EPD of MnO(2) nanoparticles and
      MWCNT. The deposition yield measurements at various experimental conditions and
      Fourier transform infrared spectroscopy data, coupled with results of electron
      microscopy, thermogravimetric, and differential thermal analysis provided
      evidence of the formation of MnO(2)-MWCNT composites. The electrochemical testing
      results and impedance spectroscopy data showed good capacitive behavior of the
      composite films and the beneficial effect of MWCNTs.

PMID- 22662972
TI  - Monsanto.

PMID- 22662971
TI  - Wiley.

PMID- 22662974
TI  - Organohalogen compounds in nature.

PMID- 22662973
TI  - ES&T: A New Forum for Research in Policy Analysis.

PMID- 22662975
TI  - ACS PUBLICATlONS.

PMID- 22662976
TI  - Es&T inquiry express.

PMID- 22662977
TI  - International.

PMID- 22662978
TI  - States.

PMID- 22662979
TI  - Science.

PMID- 22662980
TI  - Business.

PMID- 22662981
TI  - Technology.

PMID- 22662982
TI  - EPA to overhaul lab structure, boost competitive grants.

PMID- 22662983
TI  - European environment agency to begin operations.

PMID- 22662984
TI  - A Laboratory in the Sky NEW FRONTIERS IN MEASUREMENTS ALOFT.

PMID- 22662985
TI  - ACS PUBLICATlONS.

PMID- 22662986
TI  - American chemical society.

PMID- 22662987
TI  - Vertical profiling of the atmosphere using high-tech kites.

PMID- 22662988
TI  - One time opportunity!

PMID- 22662989
TI  - Great research is surfacing...

PMID- 22662990
TI  - High-Speed GC Analysis of VOCs: Tunable Selectivity and Column Selection.

PMID- 22662991
TI  - Dynamic control of wastewater treatment plants.

PMID- 22662992
TI  - Acs publications.

PMID- 22662993
TI  - A proposed approach for deriving national sediment criteria for dioxin.

PMID- 22662994
TI  - ACS Software.

PMID- 22662996
TI  - Contributors Needed for New ES&T Department.

PMID- 22662998
TI  - Instruments.

PMID- 22662999
TI  - Hazardous waste.

PMID- 22663000
TI  - Publications.

PMID- 22663001
TI  - Air pollution.

PMID- 22663002
TI  - Water treatment.

PMID- 22663003
TI  - Services.

PMID- 22663004
TI  - Water analysis.

PMID- 22663005
TI  - Software.

PMID- 22663006
TI  - Classified section.

PMID- 22663007
TI  - Acs publications.

PMID- 22663009
TI  - The department of energy.

PMID- 22663008
TI  - National university of singapore.

PMID- 22663012
TI  - Promises from trametinib in RAF active tumors.

PMID- 22663013
TI  - The relationship between mean square differences and standard error of
      measurement: comment on Barchard (2012).
AB  - In the discussion of mean square difference (MSD) and standard error of
      measurement (SEM), Barchard (2012) concluded that the MSD between 2 sets of test
      scores is greater than 2(SEM)2 and SEM underestimates the score difference
      between 2 tests when the 2 tests are not parallel. This conclusion has
      limitations for 2 reasons. First, strictly speaking, MSD should not be compared
      to SEM because they measure different things, have different assumptions, and
      capture different sources of errors. Second, the related proof and conclusions in
      Barchard hold only under the assumptions of equal reliabilities, homogeneous
      variances, and independent measurement errors. To address the limitations, we
      propose that MSD should be compared to the standard error of measurement of
      difference scores (SEMx-y) so that the comparison can be extended to the
      conditions when 2 tests have unequal reliabilities and score variances.

PMID- 22663011
TI  - Improved survival with MEK inhibition in BRAF-mutated melanoma.
AB  - BACKGROUND: Activating mutations in serine-threonine protein kinase B-RAF (BRAF)
      are found in 50% of patients with advanced melanoma. Selective BRAF-inhibitor
      therapy improves survival, as compared with chemotherapy, but responses are often
      short-lived. In previous trials, MEK inhibition appeared to be promising in this
      population. METHODS: In this phase 3 open-label trial, we randomly assigned 322
      patients who had metastatic melanoma with a V600E or V600K BRAF mutation to
      receive either trametinib, an oral selective MEK inhibitor, or chemotherapy in a
      2:1 ratio. Patients received trametinib (2 mg orally) once daily or intravenous
      dacarbazine (1000 mg per square meter of body-surface area) or paclitaxel (175 mg
      per square meter) every 3 weeks. Patients in the chemotherapy group who had
      disease progression were permitted to cross over to receive trametinib.
      Progression-free survival was the primary end point, and overall survival was a
      secondary end point. RESULTS: Median progression-free survival was 4.8 months in
      the trametinib group and 1.5 months in the chemotherapy group (hazard ratio for
      disease progression or death in the trametinib group, 0.45; 95% confidence
      interval [CI], 0.33 to 0.63; P<0.001). At 6 months, the rate of overall survival
      was 81% in the trametinib group and 67% in the chemotherapy group despite
      crossover (hazard ratio for death, 0.54; 95% CI, 0.32 to 0.92; P=0.01). Rash,
      diarrhea, and peripheral edema were the most common toxic effects in the
      trametinib group and were managed with dose interruption and dose reduction;
      asymptomatic and reversible reduction in the cardiac ejection fraction and ocular
      toxic effects occurred infrequently. Secondary skin neoplasms were not observed.
      CONCLUSIONS: Trametinib, as compared with chemotherapy, improved rates of
      progression-free and overall survival among patients who had metastatic melanoma
      with a BRAF V600E or V600K mutation. (Funded by GlaxoSmithKline; METRIC
      ClinicalTrials.gov number, NCT01245062.).

PMID- 22663015
TI  - The impact of switching on family caregivers of children with cerebral palsy.
AB  - PURPOSE: This study aimed to enhance our knowledge and understanding of
      switching, as assistive technology, and how it impacts on family caregivers of
      children with cerebral palsy with GMFCS levels four or five. METHODS: A
      qualitative method using a constructivist approach was adopted. Purposive
      sampling was used to recruit five caregivers to participants in this study.
      Framework analysis was applied to the data collection of semistructured
      interviews conducted with each caregiver. FINDINGS: The three main themes
      identified were an investment in the future, resulting in joy and hope. The
      learning process of switching is resource intensive, time consuming and effortful
      for caregivers. If caregivers do not perceive this as an investment, then they
      may not experience the joy switching can bring to their child, and in turn the
      joy, hope, and caregiver satisfaction it can offer for the future. CONCLUSION:
      This research indicates that caregivers often have the greatest impact on whether
      switching will be adopted in the home. The greatest impact on caregivers is
      related to their perception on the competence of therapists and coordination of
      services provided.

PMID- 22663014
TI  - Detection of carbon nanotubes in environmental matrices using programmed thermal
      analysis.
AB  - Carbon nanotube (CNT) production is rapidly growing, and there is a need for
      robust analytical methods to quantify CNTs at environmentally relevant
      concentrations in complex organic matrices. Because physical and thermal
      properties vary among different types of CNTs, we studied 14 single-walled
      (SWCNTs) and multiwalled CNTs (MWCNTs). Our aim was to apply a classic analytical
      air pollution method for separating organic (OC) and elemental carbon (EC)
      (thermal optical transmittance/reflectance, TOT/R) to environmental and
      biological matrices and CNTs. The TOT/R method required significant modification
      for this analysis, which required a better understanding of the thermal
      properties of CNTs. An evaluation of the thermal properties of CNTs revealed two
      classes that could be differentiated using Raman spectroscopy: thermally "weak"
      and "strong." Using the programmed thermal analysis (PTA) method, we optimized
      temperature programs and instituted a set of rules for defining the separation of
      OC and EC to quantify a broad range of CNTs. The combined Raman/PTA method was
      demonstrated using two environmentally relevant matrices (cyanobacteria (CB) and
      urban air). Thermal evaluation of CB revealed it to be a complex matrix with
      interference occurring for both weak and strong CNTs, and thus a pretreatment
      method was necessary. Strong CNT masses of 0.51, 2.7, and 11 MUg, corresponding
      to concentrations of 10, 54, and 220 MUg CNT/g CB, yielded recoveries of 160 +/-
      29%, 99 +/- 1.9%, and 96 +/- 3.0%, respectively. Urban air was also a complex
      matrix and contained a significant amount (12%) of background EC that interfered
      greatly with weak CNTs and minimally with strong CNTs. The current detection
      limit at 99% confidence for urban air samples and strong CNTs is 55 ng/m(3) (0.33
      MUg). Overall, the PTA method presented here provides an initial approach for
      quantifying a wide range of CNTs, and we identify specific future research needs
      to eliminate potential interferences and lower detection limits.

PMID- 22663016
TI  - Assessing dysphagia via telerehabilitation: patient perceptions and satisfaction.
AB  - To gain insight into factors which may influence future acceptance of dysphagia
      management via telerehabilitation, patients' perceptions were examined before and
      after a telerehabilitation assessment session. Forty adult patients with
      dysphagia (M =66 years, SD =16.25) completed pre- and post-session questionnaires
      which consisted of 14 matched questions worded to suit pre- and post-conditions.
      Questions explored comfort with the use of telerehabilitation, satisfaction with
      audio and video quality, benefits of telerehabilitation assessments and patients'
      preferred assessment modality. Questions were rated on a 5-point scale (1 =
      strongly disagree, 3 = unsure, 5 = strongly agree). Patients' comfort with
      assessment via telerehabilitation was high in over 80% of the group both pre- and
      post-assessment. Pre-assessment, patients were unsure what to expect with the
      auditory and visual aspects of the videoconference, however there were
      significant positive changes reported post-experience. In relation to perceived
      benefits of telerehabilitation services in general, most patients believed in the
      value of telerehabilitation and post-assessment this increased to 90-100%
      agreement. Although 92% felt they would be comfortable receiving services via
      telerehabilitation, 45% of patients indicated ultimate preference for a
      traditional face-to-face assessment. The data highlight that patients are
      interested in and willing to receive services via telerehabilitation; however,
      any concerns should be addressed pre-assessment.

PMID- 22663017
TI  - Longitudinal language outcomes following intrathecal chemotherapy for acute
      lymphoblastic leukaemia.
AB  - Intrathecal chemotherapy (ITC) is the treatment option for acute lymphoblastic
      leukaemia (ALL). Neurocognitive deficits have been described following ITC, but
      language status post-treatment is yet to be clarified. This study examined the
      language skills of nine children following ITC for ALL (mean age 7;8 years and
      3;2 years post-diagnosis at baseline measurement) and nine age- and sex-matched
      controls, at baseline then 2 years later, using a battery of tests assessing
      general language skills. An assessment of cognitively-demanding high level
      language skills was undertaken on a sub-group of the children (n =12).
      Statistical analysis revealed no significant difference between children treated
      with ITC and controls when comparing change in performance scores from baseline
      measurement to 2 years post-baseline measurement. Descriptive analysis of three
      of the ALL participants in the Intermediate Stage survivorship at language re
      assessment indicated no clinically-significant change in performance over 2 years
      for all measures except receptive language skills, which improved over the time
      for two of the children. As language skills continue to develop into late
      adolescence, the need for the monitoring of language abilities of children
      treated at a young age with ITC as they enter the Intermediate and Late Stages of
      survivorship is discussed.

PMID- 22663059
TI  - Gold-catalyzed cycloisomerization of 1,7-diyne benzoates to indeno[1,2-c]azepines
      and azabicyclo[4.2.0]octa-1(8),5-dines.
AB  - A synthetic method that relies on Au(I)-catalyzed cycloisomerization reactions of
      1,7-diyne benzoates to prepare indeno[1,2-c]azepines and azabicyclo[4.2.0]octa
      1(8),5-dines is described.

PMID- 22663019
TI  - Monitoring signaling by the p75(NTR) receptor utilizing a caspase-3 activation
      assay amenable to small-molecule screening.
AB  - p75(NTR) is a neurotrophin receptor that can mediate either survival or death of
      neurons depending on the cell context. Modulation of p75(NTR) is a promising
      strategy to promote neuronal survival for treatment of cognitive disorders such
      as Alzheimer's disease. Despite years of investigation into the signaling
      mechanisms of p75(NTR), no p75(NTR) signaling assay has yet been developed that
      is compatible with efficient screening of small-molecule modulators. In this
      work, we developed a homogeneous cell-based assay for screening p75(NTR)
      modulators and studying p75(NTR) function. Stimulation of p75(NTR)-transfected
      cells using either nerve growth factor (NGF) or Pro-NGF resulted in an enhanced
      caspase-3 activity as assessed by cleavage of a fluorescent caspase-3 substrate.
      Optimization of the assay with respect to time, cell density, NGF and Pro-NGF
      concentration, and other factors provided a twofold increase in the caspase-3
      activity compared to background. Withdrawal of serum during the NGF or Pro-NGF
      treatment period was found to be essential for p75(NTR)-dependent caspase-3
      activation. We validated the method by demonstrating that a signaling-incompetent
      p75(NTR) mutant could not substitute for wild-type p75(NTR) in mediating caspase
      3 activation. A focused library screen identified new inhibitors of p75(NTR)
      signaling. This method will be useful for identifying small-molecule modulators
      of p75(NTR) as well as further characterizing downstream signaling events.

PMID- 22663018
TI  - Cultural competence in end-of-life care: terms, definitions, and conceptual
      models from the British literature.
AB  - BACKGROUND: Cultural competency is increasingly recommended in policy and
      practice to improve end-of-life (EoL) care for minority ethnic groups in
      multicultural societies. It is imperative to critically analyze this approach to
      understand its underlying concepts. AIM: Our aim was to appraise cultural
      competency approaches described in the British literature on EoL care and
      minority ethnic groups. DESIGN: This is a critical review. Articles on cultural
      competency were identified from a systematic review of the literature on minority
      ethnic groups and EoL care in the United Kingdom. Terms, definitions, and
      conceptual models of cultural competency approaches were identified and situated
      according to purpose, components, and origin. Content analysis of definitions and
      models was carried out to identify key components. RESULTS: One-hundred thirteen
      articles on minority ethnic groups and EoL care in the United Kingdom were
      identified. Over half (n=60) contained a term, definition, or model for cultural
      competency. In all, 17 terms, 17 definitions, and 8 models were identified. The
      most frequently used term was "culturally sensitive," though "cultural
      competence" was defined more often. Definitions contained one or more of the
      components: "cognitive," "implementation," or "outcome." Models were categorized
      for teaching or use in patient assessment. Approaches were predominantly of
      American origin. CONCLUSIONS: The variety of terms, definitions, and models
      underpinning cultural competency approaches demonstrates a lack of conceptual
      clarity, and potentially complicates implementation. Further research is needed
      to compare the use of cultural competency approaches in diverse cultures and
      settings, and to assess the impact of such approaches on patient outcomes.

PMID- 22663060
TI  - Catalytically active silica nanoparticle-based supramolecular architectures of
      two proteins--cellobiose dehydrogenase and cytochrome C on electrodes.
AB  - Artificial nanobiomolecular architectures that follow natural examples in protein
      assembly become more and more important from basic and applied points of view.
      Our study describes the investigation on cellobiose dehydrogenase (CDH),
      cytochrome c (cyt c), and silica nanoparticles (SiNP's) for the construction of
      fully catalytically active supramolecular architectures on electrodes. We report
      on intraprotein, interprotein, and direct electron-transfer reaction cascades of
      cellobiose dehydrogenase and cytochrome c immobilized in multiple supramolecular
      layers. Carboxy-modified SiNP's are used to provide an artificial matrix, which
      enables protein arrangement in an electroactive form. Direct and interprotein
      electron transfer has been established for a two-protein system with CDH and cyt
      c in a layered architecture for the first time. We also highlight that the
      glycosylation of CDH and the silica nanoparticle size play key roles in the mode
      of operation in such a complex system. The response of the specific substrate,
      here lactose, can be tuned by the number of immobilized nanobiomolecular layers.

PMID- 22663061
TI  - Microencapsulation of hydroxyzine HCl by thermal phase separation: in vitro
      release enhancement and in vivo pharmacodynamic evaluation.
AB  - The systemic effect of hydroxyzine hydrochloride following its oral
      administration or topical application is associated with non compliant
      anticholinergic effect. Subsequently, the present study aims to prepare
      microcapsules loaded with hydroxyzine hydrochloride enabling its controlled
      release into the skin and reducing the side effect of its systemic absorption.
      The microcapsules were prepared by thermal phase separation method using ethyl
      cellulose/cyclohexane. Optimization of the formulation parameters was carried out
      by: (1) varying the type and the concentration of the coacervation inducer with
      microcapsules prepared with three different core: wall ratios, (2) by using ethyl
      cellulose with two different viscosities, (3) and by the addition of pore
      inducers such as pregelatinized starch and sucrose in order to enhance the drug
      release. Microcapsules of 99% encapsulation efficiency were prepared using 1% w/v
      polyisobutylene, and 1:0.1 core: wall ratio. The highest percent of drug is
      released after 9 h from microcapsules prepared using 1:0.1 core :wall ratio.
      Almost 100% drug was released after 3 h, from the same microcapsules prepared
      with pregelatinized starch that acts as a core coated with the drug. The
      pharmacodynamic effect of the chosen preparation was tested on the shaved back of
      histamine sensitized rabbits. Histopathological studies were driven for the
      detection of the healing of inflamed tissues.

PMID- 22663062
TI  - Quantum yield and mechanism of singlet oxygen generation via UV photoexcitation
      of O2-O2 and N2-O2 encounter complexes.
AB  - The mechanism and spectral dependence of the quantum yield of singlet oxygen
      O(2)(a (1)Delta(g)) photogenerated by UV radiation in gaseous oxygen at elevated
      pressure (32-130 bar) have been experimentally investigated within the 238-285 nm
      spectral region overlapping the range of the Wulf bands in the absorption
      spectrum of oxygen. The dominant channel of singlet oxygen generation with
      measured quantum yield up to about 2 is attributed to the one-quantum absorption
      by the encounter complexes O(2)-O(2). This absorption gives rise to oxygen in the
      Herzberg III state O(2)(A' (3)Delta(u)), which is assumed to be responsible for
      singlet oxygen production in the relaxation process O(2)(A' (3)Delta(u), upsilon)
      + O(2)(X (3)Sigma(g)(-)) -> O(2)({a (1)Delta(g)}, {b (1)Sigma(g)(+)}) + O(2)({a
      (1)Delta(g), upsilon = 0}, {b (1)Sigma(g)(+), upsilon = 0}) with further
      collisional relaxation of b to a state. This mechanism is deduced from the
      analysis of the avoiding crossing locations on the potential energy surface of
      colliding O(2)-O(2) pair. The observed drop of the O(2)(a (1)Delta(g)) yield near
      spectral threshold for O(2) dissociation is explained by the competition between
      above relaxation and reaction giving rise to O(3) + O (O + O + O(2)) supposed in
      literature. The quantum yield of O(2)(a (1)Delta(g)) formation from encounter
      complex N(2)-O(2) measured at lambda = 266 nm was found to be the same as that
      for O(2)-O(2).

PMID- 22663063
TI  - Synthesis and photocatalytic activity of single-crystalline hollow rh-In2O3
      nanocrystals.
AB  - We report here for the first time the hollow, metastable, single-crystal,
      rhombohedral In(2)O(3) (rh-In(2)O(3)) nanocrystals synthesized by annealing
      solvothermally prepared InOOH solid nanocrystals under ambient pressure at 400 
      degrees C, through a mechanism of the Kirkendall effect, in which pore formation
      is attributed to the difference in diffusion rates of anions (OH(-) and O(2-)) in
      a diffusion couple. The InOOH solid nanocrystals were prepared via a controlled
      hydrolysis solvothermal route by using In(NO(3))(3).4.5H(2)O as a starting
      material and glycerol-ethanol as a mixed solvent. The glycerol-ethanol mixed
      solvent plays a key role on the formation of the intermediate InOOH, thus the
      final product of rh-In(2)O(3). The as-synthesized In(2)O(3) nanocrystals present
      excellent photocatalytic degradation of rhodamine B (RhB) and methylene blue (MB)
      dyes, which present ~92% degradation of RhB or MB after 4 or 3 h reaction in the
      presence of the as-synthesized In(2)O(3) nanocrystals, respectively.

PMID- 22663064
TI  - Asymmetric total synthesis of cladosporin and isocladosporin.
AB  - The first asymmetric total syntheses of cladosporin and isocladosporin were
      accomplished in 8 steps with 8% overall yield and 10 steps with 26% overall
      yield, respectively. The relative configuration of isocladosporin was determined
      via this total synthesis.

PMID- 22663065
TI  - Selective catalytic sp3 C-O bond cleavage with C-N bond formation in 3-alkoxy-1
      propanols.
AB  - The ruthenium catalyzed selective sp(3) C-O cleavage with amide formation was
      reported in reactions of 3-alkoxy-1-propanol derivatives and amines. The cleavage
      only occurs at the C3-O position even with 3-benzyloxy-1-propanol. Based on the
      experimental results, O-bound and C-bound Ru enolate complexes were proposed as
      key intermediates for the unique selective sp(3) C-O bond cleavage in 3-alkoxy-1
      propanols.

PMID- 22663066
TI  - Biofunctionalization of 3D nylon 6,6 scaffolds using a two-step surface
      modification.
AB  - Nylon is a relatively inert polymer. The ability to easily functionalize nylon
      with biomolecules will improve the utilization of nylon in biological systems. A
      potential use of the biofunctionalized nylon scaffolds is in devices for cell
      therapeutics that can specifically select cells present in small numbers, such as
      hematopoietic stem cells. This study developed a versatile and simple two-step
      technique combining oxygen plasma treatment with wet silanization to graft
      biomolecules onto nylon 6,6 3D porous scaffolds. Scaffolds that were exposed to
      oxygen plasma exhibited up to 13-fold increase in silane attachment ((3
      mercaptopropyl)trimethoxysilane/(3-aminopropyl)trimethoxysilane) compared to
      untreated scaffolds. To address the limitation of nondestructive characterization
      of the surface chemistry of 3D scaffolds, fluorescent CdSe/ZnS nanoparticles were
      used as a reporting tool for -NH2 functionalized surfaces. Scaffolds that were
      covalently bound with neutravidin protein remained stable in phosphate buffered
      saline up to four months. Functionality of the neutravidin-grafted scaffolds was
      demonstrated by the specific binding of CD4 cells to the scaffold via CD4
      specific antibody. Ultimately, these neutravidin-functionalized 3D nylon
      scaffolds could be easily customized on demand utilizing a plethora of
      biotinylated biomolecules (antibodies, enzymes and proteins) to select for
      specific cell of interest. This technique can be extended to other applications,
      including the enhancement of cell-scaffold interactions. 

PMID- 22663067
TI  - Liberation of copper from amyloid plaques: making a risk factor useful for
      Alzheimer's disease treatment.
AB  - Alzheimer's disease (AD) is a complex multifactorial syndrome. Metal chelator and
      Abeta inhibitor are showing promise against AD. In this report, three small
      hybrid compounds (1, 2, and 3) have been designed and synthesized utilizing
      salicylaldehyde (SA) based Schiff bases as the chelators and benzothiazole (BT)
      as the recognition moiety for AD treatment. These conjugates can capture Cu(2+)
      from Abeta and become dimers upon Cu(2+) coordination and show high efficiency
      for both Cu(2+) elimination and Abeta assembly inhibition. Besides, the complexes
      have superoxide dismutase (SOD) activity and significant antioxidant capacity and
      are capable of decreasing intracellular reactive oxygen species (ROS) and
      increasing cell viability. All these results indicate that the multifunctional
      metal complexes which have Abeta specific recognition moiety and metal ion
      chelating elements show the potential for AD treatment. Therefore, our work will
      provide new insights into exploration of more potent amyloid inhibitors.

PMID- 22663068
TI  - Oxidation of phosphorus centers by ferrate(VI): spectral observation of an
      intermediate.
AB  - The kinetics and mechanism for the oxidation of phosphite, hypophosphite,
      phenylphosphite, and trimethylphosphite by ferrate(VI) are reported.
      Hypophosphite is rapidly oxidized to phosphite which is slowly oxidized to
      phosphate, trimethylphosphite is oxidized to trimethylphosphate, and
      phenylphosphite is oxidized phenylphosphate. (18)O induced shifts of the (31)P
      NMR signals support oxygen transfer from ferrate(VI) to the phosphorus center
      during the oxidation process. Deuteration of the hydridic hydrogens in
      hypophosphite and phosphite resulted in significant kinetic isotope effects on
      the reaction rates. It is proposed that ferrate(VI) acts as a two-electron
      oxidant in conjunction with oxide transfer coupled with phosphorus hydrogen bond
      breaking for phosphite and hypophosphite and simple oxygen transfer for
      trimethylphosphite and phenylphosphite.

PMID- 22663072
TI  - Thermal diffusion of nucleotides.
AB  - We investigate the thermal diffusion behavior of aqueous solutions of nucleotides
      using an infrared thermal diffusion forced Rayleigh scattering (IR-TDFRS) setup.
      In this work we study 5 nucleotides: cyclic nucleotides adenosine and guanosine
      monophosphate, 5'-adenosine and 5'-cytidine monophosphate, and also adenosine
      diphosphate in water. The structures of nucleotides vary systematically, which
      results in different physical properties such as acidity, solubility,
      hydrophobicity, and melting point. We discuss the connection between the thermal
      diffusion behavior and the properties of the different nucleotides. Additionally,
      as in the case of the alkanes and monoscaccharides, we find a correlation between
      the thermal diffusion coefficient and the ratio of the thermal expansion
      coefficient and the kinematic viscosity.

PMID- 22663073
TI  - Rapid determination of the attenuation limit of beer using middle-infrared (MIR)
      spectroscopy and a multivariate model.
AB  - A new approach for the determination of the attenuation limit of beer samples
      using the specific fingerprint region of middle-infrared (MIR) spectroscopy in
      combination with multiple regression by partial least-squares (PLS) was developed
      using an attenuated total reflectance (ATR) module. A specific spectral region
      between 1200 and 800 cm(-1) was identified as highly informative for the
      quantification of the limit of attenuation. The absorptions in this region are
      induced by vibrational bands of ethanol (1080, 1040, and 880 cm(-1)) and
      dissolved extract, in majority maltotriose (1160-1140 and 1040-980 cm(-1)). The
      multivariate calibration results in a root mean squared error of calibration
      (RMSEC) of 0.40% and a validation procedure with independent samples results in a
      root mean squared error of validation (RMSEV) of 0.50%. A repeatability test,
      concerning the precision of the developed MIR method as well as the reference
      method, was analyzed using Student's t test. The test has shown no significant
      difference between the two random samples.

PMID- 22663074
TI  - Contextual influences of parenting behaviors for children with neurodevelopmental
      disorders: results from a Canadian national survey.
AB  - PURPOSE: This population-based study examined correlates of three parenting
      behaviors (positive interactions, consistency, and ineffective parenting) that
      have been shown to differ in children with neurodevelopmental disorders (NDDs),
      with and without externalizing behavior problems (EBPs), as compared to children
      with neither condition. METHOD: The sample of children aged 4-11 (N = 14,226) was
      drawn from the Canadian National Longitudinal Survey of Children and Youth
      (NLSCY). Analyses examined the associations of child, parental, and social
      context factors with parenting behaviors, and whether they differed by child
      health group. RESULTS: Child age, family functioning, and social support
      variables were significant predictors of all three parenting behaviors.
      Significant interaction effects highlight the importance of the child's sex,
      birth order, and support received from community or social service professionals,
      and that these factors have differential impacts on parenting behaviors depending
      on the child's health group. CONCLUSIONS: Other Child, parent, and social context
      factors are associated with parenting behaviors but these associations vary by
      the child's health group. Parenting behaviors differ for children with NDDs with
      and without EBPs. These findings offer important implications for practice and
      research and point to the importance of considering multiple contexts of
      influence, as well as their interactions, in understanding differences in
      parenting behaviors.

PMID- 22663075
TI  - Learning stable, regularised latent models of neural population dynamics.
AB  - Ongoing advances in experimental technique are making commonplace simultaneous
      recordings of the activity of tens to hundreds of cortical neurons at high
      temporal resolution. Latent population models, including Gaussian-process factor
      analysis and hidden linear dynamical system (LDS) models, have proven effective
      at capturing the statistical structure of such data sets. They can be estimated
      efficiently, yield useful visualisations of population activity, and are also
      integral building-blocks of decoding algorithms for brain-machine interfaces
      (BMI). One practical challenge, particularly to LDS models, is that when
      parameters are learned using realistic volumes of data the resulting models often
      fail to reflect the true temporal continuity of the dynamics; and indeed may
      describe a biologically-implausible unstable population dynamic that is, it may
      predict neural activity that grows without bound. We propose a method for
      learning LDS models based on expectation maximisation that constrains parameters
      to yield stable systems and at the same time promotes capture of temporal
      structure by appropriate regularisation. We show that when only little training
      data is available our method yields LDS parameter estimates which provide a
      substantially better statistical description of the data than alternatives,
      whilst guaranteeing stable dynamics. We demonstrate our methods using both
      synthetic data and extracellular multi-electrode recordings from motor cortex.

PMID- 22663076
TI  - A mitochondrial odyssey.
AB  - Good fortune let me be an innocent child during World War II, a hopeful
      adolescent with encouraging parents during the years of German recovery, and a
      self-determined adult in a period of peace, freedom, and wealth. My luck
      continued as a scientist who could entirely follow his fancy. My mind was always
      set on understanding how things are made. At a certain point, I found myself
      confronted with the question of how mitochondria and organelles, which cannot be
      formed de novo, are put together. Intracellular transport of proteins, their
      translocation across the mitochondrial membranes, and their folding and assembly
      were the processes that fascinated me. Now, after some 30 years, we have
      wonderful insights, unimagined views of a complex and at the same time simple
      machinery and its workings. We have glimpses of how orderly processes are
      established in the cell to assemble from single molecules our beautiful
      mitochondria that every day make some 50 kg of ATP for each of us. At the same
      time, we have learned amazing lessons from the tinkering of evolution that
      developed mitochondria from bacteria.

PMID- 22663079
TI  - The ubiquitin system, an immense realm.

PMID- 22663078
TI  - Genome regulation by long noncoding RNAs.
AB  - The central dogma of gene expression is that DNA is transcribed into messenger
      RNAs, which in turn serve as the template for protein synthesis. The discovery of
      extensive transcription of large RNA transcripts that do not code for proteins,
      termed long noncoding RNAs (lncRNAs), provides an important new perspective on
      the centrality of RNA in gene regulation. Here, we discuss genome-scale
      strategies to discover and characterize lncRNAs. An emerging theme from multiple
      model systems is that lncRNAs form extensive networks of ribonucleoprotein (RNP)
      complexes with numerous chromatin regulators and then target these enzymatic
      activities to appropriate locations in the genome. Consistent with this notion,
      lncRNAs can function as modular scaffolds to specify higher-order organization in
      RNP complexes and in chromatin states. The importance of these modes of
      regulation is underscored by the newly recognized roles of long RNAs for proper
      gene control across all kingdoms of life.

PMID- 22663077
TI  - The COMPASS family of histone H3K4 methylases: mechanisms of regulation in
      development and disease pathogenesis.
AB  - The Saccharomyces cerevisiae Set1/COMPASS was the first histone H3 lysine 4
      (H3K4) methylase identified over 10 years ago. Since then, it has been
      demonstrated that Set1/COMPASS and its enzymatic product, H3K4 methylation, is
      highly conserved across the evolutionary tree. Although there is only one COMPASS
      in yeast, Drosophila possesses three and humans bear six COMPASS family members,
      each capable of methylating H3K4 with nonredundant functions. In yeast, the
      histone H2B monoubiquitinase Rad6/Bre1 is required for proper H3K4 and H3K79
      trimethylations. The machineries involved in this process are also highly
      conserved from yeast to human. In this review, the process of histone H2B
      monoubiquitination-dependent and -independent histone H3K4 methylation as a mark
      of active transcription, enhancer signatures, and developmentally poised genes is
      discussed. The misregulation of histone H2B monoubiquitination and H3K4
      methylation result in the pathogenesis of human diseases, including cancer.
      Recent findings in this regard are also examined.

PMID- 22663080
TI  - Structural perspective of peptidoglycan biosynthesis and assembly.
AB  - The peptidoglycan biosynthetic pathway is a critical process in the bacterial
      cell and is exploited as a target for the design of antibiotics. This pathway
      culminates in the production of the peptidoglycan layer, which is composed of
      polymerized glycan chains with cross-linked peptide substituents. This layer
      forms the major structural component of the protective barrier known as the cell
      wall. Disruption in the assembly of the peptidoglycan layer causes a weakened
      cell wall and subsequent bacterial lysis. With bacteria responsible for both
      properly functioning human health (probiotic strains) and potentially serious
      illness (pathogenic strains), a delicate balance is necessary during clinical
      intervention. Recent research has furthered our understanding of the precise
      molecular structures, mechanisms of action, and functional interactions involved
      in peptidoglycan biosynthesis. This research is helping guide our understanding
      of how to capitalize on peptidoglycan-based therapeutics and, at a more
      fundamental level, of the complex machinery that creates this critical barrier
      for bacterial survival.

PMID- 22663082
TI  - Two dimensional soft material: new faces of graphene oxide.
AB  - Graphite oxide sheets, now called graphene oxide (GO), can be made from chemical
      exfoliation of graphite by reactions that have been known for 150 years. Because
      GO is a promising solution-processable precursor for the bulk production of
      graphene, interest in this old material has resurged. The reactions to produce GO
      add oxygenated functional groups to the graphene sheets on their basal plane and
      edges, and this derivatization breaks the pi-conjugated network, resulting in
      electrically insulating but highly water-dispersible sheets.  Apart from making
      graphene, GO itself has many intriguing properties. Like graphene, GO is a two
      dimensional (2D) sheet with feature sizes at two abruptly different length
      scales. The apparent thickness of the functionalized carbon sheet is
      approximately 1 nm, but the lateral dimensions can range from a few nanometers to
      hundreds of micrometers. Therefore, researchers can think of GO as either a
      single molecule or a particle, depending on which length scale is of greater
      interest. At the same time, GO can be viewed as an unconventional soft material,
      such as a 2D polymer, highly anisotropic colloid, membrane, liquid crystal, or
      amphiphile.  In this Account, we highlight the soft material characteristics of
      GO. GO consists of nanographitic patches surrounded by largely disordered,
      oxygenated domains. Such structural characteristics effectively make GO a 2D
      amphiphile with a hydrophilic periphery and largely hydrophobic center. This
      insight has led to better understanding of the solution properties of GO for
      making thin films and new applications of GO as a surfactant. Changes in pH and
      sheet size can tune the amphiphilicity of GO, leading to intriguing interfacial
      activities. In addition, new all-carbon composites made of only graphitic
      nanostructures using GO as a dispersing agent have potential applications in
      photovoltaics and energy storage. On the other hand, GO can function as a 2D
      random diblock copolymer, one block graphitic and the other heavily hydroxylated.
      Therefore, GO can guide material assembly through pi-pi stacking and hydrogen
      bonding. Additionally, the selective etching of the more reactive sp(3) blocks
      produces a porous GO network, which greatly enhances interactions with gas
      molecules in chemical sensors. With their high aspect ratio, GO colloids can
      readily align to form liquid crystalline phases at high concentration.  As single
      atomic, water-dispersible, soft carbon sheets that can be easily converted to a
      conductive form, this 2D material should continue to inspire many curiosity
      driven discoveries and applications at the interfaces of chemistry, materials
      science, and other disciplines.

PMID- 22663081
TI  - Roles for actin assembly in endocytosis.
AB  - Endocytosis includes a number of processes by which cells internalize segments of
      their plasma membrane, enclosing a wide variety of material from outside the
      cell. Endocytosis can contribute to uptake of nutrients, regulation of signaling
      molecules, control of osmotic pressure, and function of synapses. The actin
      cytoskeleton plays an essential role in several of these processes. Actin
      assembly can create protrusions that encompass extracellular materials. Actin can
      also support the processes of invagination of a membrane segment into the
      cytoplasm, elongation of the invagination, scission of the new vesicle from the
      plasma membrane, and movement of the vesicle away from the membrane. We briefly
      discuss various types of endocytosis, including phagocytosis, macropinocytosis,
      and clathrin-independent endocytosis. We focus mainly on new findings on the
      relative importance of actin in clathrin-mediated endocytosis (CME) in yeast
      versus mammalian cells.

PMID- 22663084
TI  - Measurement of the product attitudes of youth during the selection of assistive
      technology devices.
AB  - PURPOSE: This article proposes a conceptual underpinning for and examines the
      validity of the Youth Evaluation of Products (YEP) scale when used to measure the
      AT device attitudes of youth. METHOD: Consumer socialization is promoted to
      improve the utility of an AT device selection framework for children and youth
      and inform the development of the YEP scale. A descriptive, qualitative mixed
      methods design explored the validity of the scale when used by six manual
      wheelchair users, aged 11-14 years, to evaluate a new pushrim-activated, power
      assisted wheelchair. Three youth participated in a subsequent focus group to
      share how they assessed wheelchair products. RESULTS: The items and dimensions of
      the YEP scale corresponded well to participants' views about wheelchairs.
      CONCLUSIONS: Consumer socialization provides a new way to understand the
      developing role of youth as AT consumers and the YEP scale is emerging as a way
      to measure their product attitudes. When integrated with contemporary thinking
      about the assessment and selection of AT devices, providers and parents may be
      better able to incorporate the product perspectives of youth during this shared
      decision-making process. [Box: see text].

PMID- 22663083
TI  - Comparing Symptom Burden in Patients with Metastatic and Nonmetastatic Cancer.
AB  - BACKGROUND: Symptoms of patients with advanced cancer have been extensively
      studied, but less attention has been paid to the symptomatology of patients with
      localized disease. We compared the symptom burden of outpatients with cancer,
      either metastatic or localized disease, seen in a palliative care comanagement
      clinic. METHODS: We conducted a retrospective, cross-sectional study assessing
      patient symptoms with multiple patient surveys, including a modified Edmonton
      Symptom Assessment Survey (to assess pain, fatigue, anxiety, depression, and
      nausea), along with a spiritual well-being screen and questions about
      relationships and quality of life. Consecutive patients at a comprehensive cancer
      center completed the surveys prior to their first visit to an outpatient
      palliative care clinic providing palliative care concurrently with the patients'
      oncologic treatments. Patients were referred by their oncologist, radiation
      oncologist, oncologic surgeon, or primary care physician without respect to their
      stage or prognosis. Statistical analyses used were chi(2), Fisher's exact test,
      Student's t test, and multivariate linear regression. Significance was taken as
      p<0.05. RESULTS: Two hundred and five patients were included in this study. One
      hundred and twenty-seven patients (62%) had metastatic cancer and 78 (38%) had
      nonmetastatic cancer. The characteristics of the two study groups were similar
      with regard to age, sex, ethnicity, language, religion, partnership status, and
      insurance status. Patients with metastatic disease and localized disease had
      similar mean symptom burden and mean individual symptom intensity for all
      symptoms evaluated except for nausea, which was worse in patients with metastatic
      disease (3.4 versus 2.5, p=0.0028). Nausea was also worse in younger patients.
      CONCLUSION: Among patients referred to a cancer center outpatient palliative care
      clinic, symptom burden is similar in patients with localized and metastatic
      disease. Even patients with relatively good prognoses may nevertheless have
      significant symptom burdens in physical, emotional, and existential domains. The
      palliative care needs of all patients must be assessed, regardless of stage or
      prognosis.

PMID- 22663085
TI  - High performance thin-film composite forward osmosis hollow fiber membranes with
      macrovoid-free and highly porous structure for sustainable water production.
AB  - The development of high-performance and well-constructed thin-film composite
      (TFC) hollow fiber membranes for forward osmosis (FO) applications is presented
      in this study. The newly developed membranes consist of a functional selective
      polyamide layer formed by highly reproducible interfacial polymerization on a
      polyethersulfone (PES) hollow fiber support. Using dual-layer coextrusion
      technology to design and effectively control the phase inversion during membrane
      formation, the support was designed to possess desirable macrovoid-free and fully
      sponge-like morphology. Such morphology not only provides excellent membrane
      strength, but it has been proven to minimize internal concentration polarization
      in a FO process, thus leading to the water flux enhancement. The fabricated
      membranes exhibited relatively high water fluxes of 32-34 LMH and up to 57-65 LMH
      against a pure water feed using 2 M NaCl as the draw solution tested under the FO
      and pressure retarded osmosis (PRO) modes, respectively, while consistently
      maintaining relatively low salt leakages below 13 gMH for all cases. With model
      seawater solution as the feed, the membranes could display a high water flux up
      to 15-18 LMH, which is comparable to the best value reported for seawater
      desalination applications.

PMID- 22663087
TI  - Synthesis, crystal chemistry, and magnetic properties of RE7Li8Ge10 and
      RE11Li12Ge16 (RE = La-Nd, Sm): new members of the [REGe2](n)[RELi2Ge](m)
      homologous series.
AB  - Eight new rare-earth metal-lithium-germanides belonging to the
      [REGe(2)](n)[RELi(2)Ge](m) homologous series have been synthesized and
      structurally characterized by single-crystal X-ray diffraction. The structures of
      the title compounds can be rationalized as linear intergrowths of imaginary
      RELi(2)Ge (MgAl(2)Cu structure type) and REGe(2) (AlB(2) structure type) slabs.
      The compounds with general formula RE(7)Li(8)Ge(10) (RE = La-Nd, Sm), i.e.,
      [REGe(2)](3)[RELi(2)Ge](4), crystallize in the orthorhombic space group Cmmm (No.
      65) with a new structure type. Similarly, the compounds with general formula
      RE(11)Li(12)Ge(16) (RE = Ce-Nd), i.e., [REGe(2)](5)[RELi(2)Ge](6), crystallize in
      the orthorhombic space group Immm (No. 71) also with its own structure type.
      Temperature-dependent DC magnetization measurements indicate Curie-Weiss
      paramagnetism in the high-temperature regime and hint at complex magnetic
      ordering at low temperatures. The measured effective moments are consistent with
      RE(3+) ground states in all cases. The experimental results have been
      complemented by tight-binding linear muffin-tin orbital (TB-LMTO) electronic
      structure calculations.

PMID- 22663086
TI  - Promotion of phenol photodecomposition over TiO2 using Au, Pd, and Au-Pd
      nanoparticles.
AB  - Noble metal nanoparticles (Au, Pd, Au-Pd alloys) with a narrow size distribution
      supported on nanocrystalline TiO(2) (M/TiO(2)) have been synthesized via a sol
      immobilization route. The effect of metal identity and size on the photocatalytic
      performance of M/TiO(2) has been systematically investigated using phenol as a
      probe molecule. A different phenol degradation pathway was observed when using
      M/TiO(2) catalysts as compared to pristine TiO(2). We propose a mechanism to
      illustrate how the noble metal nanoparticles enhance the efficiency of phenol
      decomposition based on photoreduction of p-benzoquinone under anaerobic
      conditions. Our results suggest that the metal nanoparticles not only play a role
      in capturing photogenerated electrons, but are strongly involved in the
      photocatalytic reaction mechanism. The analysis of the reaction intermediates
      allows us to conclude that on M/TiO(2) undesired redox reactions that consume
      photogenerated radicals are effectively suppressed. The analysis of the final
      products shows that the reusability performance of the catalyst is largely
      dependent on the pretreatment of the catalyst and the identity of the metal
      nanoparticle. Interestingly, the as-prepared Pd and Au-Pd decorated TiO(2)
      materials exhibit excellent long-term photoactivity, in which ~90% of the phenol
      can be fully decomposed to CO(2) in each cycle.

PMID- 22663088
TI  - Efficient photon capturing with ordered three-dimensional nanowell arrays.
AB  - Unique light-matter interaction at nanophotonic regime can be harnessed for
      designing efficient photonic and optoelectronic devices such as solar cells,
      lasers, and photodetectors. In this work, periodic photon nanowells are
      fabricated with a low-cost and scalable approach, followed by systematic
      investigations of their photon capturing properties combining experiments and
      simulations. Intriguingly, it is found that a proper periodicity greatly
      facilitates photon capturing process in the nanowells, primarily owing to optical
      diffraction. Meanwhile, the nanoengineered morphology renders the nanostructures
      with a broad-band efficient light absorption. The findings in this work can be
      utilized to implement a new type of nanostructure-based solar cells. Also, the
      methodology applied in this work can be generalized to rational design of other
      types of efficient photon-harvesting devices.

PMID- 22663089
TI  - Pharmaceutical evaluation and dynamic vapor sorption studies of fast dissolving
      intraoral films of Loratadine.
AB  - The aim of the study was to develop intraoral films (IOFs) of loratadine and to
      assess the storage conditions by dynamic vapour sorption studies. The excipient
      selection was guided by drug excipient compatibility studies and the
      incompatibility of loratadine with dibutylphathalate and Tween20 was confirmed by
      Electro-spray Ionization Mass Spectrometry. Thus intaroral films were developed
      using HPMC E-15 LV and polyvinyl alcohol (PVA) as lone and mixed film formers to
      get eighteen formulations (F1- F18) that varied in the type and amount of
      plasticizer used. Four formulations selected on the basis of pharmacotechnical
      characteristics were improvised by inclusion of Poloxamer407 that lowered the
      dissolving time to the tune of 36-55%. Dynamic vapour sorption studies of the
      improvised films (PF1-PF4) demonstrated an increase of 2% by weight at 50%
      relative humidity (RH) and 25 degrees C suggesting storage of the films below the
      stated conditions. In vitro drug release studies in phosphate buffer pH 6.8
      demonstrated more than 94% cumulative drug release from the formulations.
      Analysis of model independent parameters identified PF2 as the best formulation
      that was nine times superior in its dissolution efficiency to Lorafast
      tablets((r)). 

PMID- 22663090
TI  - Synthesis of the aminocyclitol units of (-)-hygromycin A and methoxyhygromycin
      from myo-inositol.
AB  - Concise and efficient syntheses of the aminocyclitol cores of hygromycin A (HMA)
      and methoxyhygromycin (MHM) have been achieved starting from readily available
      myo-inositol. Reductive cleavage of myo-inositol orthoformate to the
      corresponding 1,3-acetal, stereospecific introduction of the amino group via the
      azide, and resolution of a racemic cyclitol derivative as its diastereomeric
      mandelate esters are the key steps in the synthesis. Synthesis of the
      aminocyclitol core of hygromycin A involved chromatography in half of the total
      number of steps, and the aminocyclitol core of methoxyhygromycin involved only
      one chromatography.

PMID- 22663091
TI  - Group electronegativity for prediction of materials hardness.
AB  - We have developed a method to predict the hardness of materials containing
      ultrastrong anionic polyhedra, dense atomic clusters, and layers stacked through
      van der Waals bonds on the basis of group electronegativity. By considering these
      polyhedra, clusters, and layers as groups that behave as rigid unities like
      superatoms bonding to other atoms or groups, the hardness values of materials
      such as oxysalts, T-carbon, and graphite were quantitatively calculated, and the
      results are consistent with the available experiments. We found that the hardness
      of materials containing these artificial groups is determined by the bonds
      between the groups and other atoms or groups, rather than by the weakest bonds.
      This work sheds light on the nature of materials hardness and the design of novel
      inorganic crystal materials.

PMID- 22663092
TI  - Thermodynamics of electron flow in the bacterial deca-heme cytochrome MtrF.
AB  - Electron-transporting multi-heme cytochromes are essential to the metabolism of
      microbes that inhabit soils and carry out important biogeochemical processes.
      Recently the first crystal structure of a prototype bacterial deca-heme
      cytochrome (MtrF) has been resolved and its electrochemistry characterized.
      However, the molecular details of electron transport along heme chains in the
      cytochrome are difficult to access via experiment due to the nearly identical
      chemical nature of the heme cofactors. Here we employ large-scale molecular
      dynamics simulations to compute the redox potentials of the 10 hemes of MtrF in
      aqueous solution. We find that as a whole they fall within a range of ~0.3 V, in
      agreement with experiment. Individual redox potentials give rise to a free energy
      profile for electron transport that is approximately symmetric with respect to
      the center of the protein. Our calculations indicate that there is no significant
      potential bias along the orthogonal octa- and tetra-heme chains, suggesting that
      under aqueous conditions MtrF is a nearly reversible two-dimensional conductor.

PMID- 22663094
TI  - Excretion profiles and half-lives of ten urinary polycyclic aromatic hydrocarbon
      metabolites after dietary exposure.
AB  - Human exposure to polycyclic aromatic hydrocarbons (PAHs) can be assessed by
      biomonitoring of their urinary monohydroxylated metabolites (OH-PAHs). Limited
      information exists on the human pharmacokinetics of OH-PAHs. This study aimed to
      investigate the excretion half-life of 1-hydroxypyrene (1-PYR), the most used
      biomarker for PAH exposure, and 9 other OH-PAHs following a dietary exposure in 9
      nonsmoking volunteers with no occupational exposure to PAHs. Each person avoided
      food with known high PAH-content during the study period, except for a high PAH
      containing lunch (barbecued chicken) on the first day. Individual urine samples
      (n = 217) were collected from 15 h before to 60 h following the dietary exposure.
      Levels of all OH-PAHs in all subjects increased rapidly by 9-141-fold after the
      exposure, followed by a decrease consistent with first-order kinetics, and
      returned to background levels 24-48 h after the exposure. The average time to
      reach maximal concentration ranged from 3.1 h (1-naphthol) to 5.5 h (1-PYR).
      Creatinine-adjusted urine concentrations for each metabolite were analyzed using
      a nonlinear mixed effects model including a term to estimate background exposure.
      The background-adjusted half-life estimate was 3.9 h for 1-PYR and ranged 2.5-6.1
      h for the other 9 OH-PAHs, which in general, were shorter than those previously
      reported. The maximum concentrations after barbecued chicken consumption were
      comparable to the levels found in reported occupational settings with known high
      PAH exposures. It is essential to consider the relatively short half-life, the
      timing of samples relative to exposures, and the effect of diet when conducting
      PAH exposure biomonitoring studies.

PMID- 22663136
TI  - Estimates of increased black carbon emissions from electrostatic precipitators
      during powdered activated carbon injection for mercury emissions control.
AB  - The behavior of mercury sorbents within electrostatic precipitators (ESPs) is not
      well-understood, despite a decade or more of full-scale testing. Recent
      laboratory results suggest that powdered activated carbon exhibits somewhat
      different collection behavior than fly ash in an ESP and particulate filters
      located at the outlet of ESPs have shown evidence of powdered activated carbon
      penetration during full-scale tests of sorbent injection for mercury emissions
      control. The present analysis considers a range of assumed differential ESP
      collection efficiencies for powdered activated carbon as compared to fly ash.
      Estimated emission rates of submicrometer powdered activated carbon are compared
      to estimated emission rates of particulate carbon on submicrometer fly ash, each
      corresponding to its respective collection efficiency. To the extent that any
      emitted powdered activated carbon exhibits size and optical characteristics
      similar to black carbon, such emissions could effectively constitute an increase
      in black carbon emissions from coal-based stationary power generation. The
      results reveal that even for the low injection rates associated with chemically
      impregnated carbons, submicrometer particulate carbon emissions can easily double
      if the submicrometer fraction of the native fly ash has a low carbon content.
      Increasing sorbent injection rates, larger collection efficiency differentials as
      compared to fly ash, and decreasing sorbent particle size all lead to increases
      in the estimated submicrometer particulate carbon emissions.

PMID- 22663096
TI  - Isolation of spirastrellolides A and B from a marine sponge Epipolasis sp. and
      their cytotoxic activities.
AB  - Spirastrellolides A (1) and B (3) have been isolated as free acids from a marine
      sponge Epipolasis sp. collected in the East China Sea. These compounds had been
      isolated from the Caribbean marine sponge Spirastrella coccinea after conversion
      to the methyl ester. We examined the cytotoxic activities of 1 and 3 and found
      that the activities of the free acids are comparable to those of the
      corresponding methyl esters.

PMID- 22663095
TI  - Thick acellular heart extracellular matrix with inherent vasculature: a potential
      platform for myocardial tissue regeneration.
AB  - The decellularization of porcine heart tissue offers many opportunities for the
      production of physiologically relevant myocardial mimetic scaffolds. Earlier, we
      reported the successful isolation of a thin porcine cardiac extracellular matrix
      (pcECM) exhibiting relevant bio-mechanical properties for myocardial tissue
      engineering. Nevertheless, since native cardiac tissue is much thicker, such thin
      scaffolds may offer limited regeneration capacity. However, generation of thicker
      myocardial mimetic tissue constructs is hindered by diffusion limitations (~100
      MUm), and the lack of a proper vascular-like network within these constructs. In
      our present work, we focused on optimizing the decellularization procedure for
      thicker tissue slabs (10-15 mm), while retaining their inherent vasculature, and
      on characterizing the resulting pcECM. The trypsin/Triton-based perfusion
      procedure that resulted in a nonimmunogenic and cell-supportive pcECM was found
      to be more effective in cell removal and in the preservation of fiber morphology
      and structural characteristics than stirring, sonication, or sodium dodecyl
      sulfate/Triton-based procedures. Mass spectroscopy revealed that the pcECM is
      mainly composed of ECM proteins with no apparent cellular protein remains.
      Mechanical testing indicated that the obtained pcECM is viscoelastic in nature
      and possesses the typical stress-strain profile of biological materials. It is
      stiffer than native tissue yet exhibits matched mechanical properties in terms of
      energy dissipation, toughness, and ultimate stress behavior. Vascular network
      functionality was maintained to the first three-four branches from the main
      coronary vessels. Taken together, these results reaffirm the efficiency of the
      decellularization procedure reported herein for yielding thick nonimmunogenic
      cell-supportive pcECM scaffolds, preserving both native tissue ultra-structural
      properties and an inherent vascular network. When reseeded with the appropriate
      progenitor cells, these scaffolds can potentially serve as ex vivo screening
      platforms for new therapeutics, as models for human cardiac ECM, or as biomedical
      constructs for patch or transmural transplantation strategies.

PMID- 22663137
TI  - Bevacizumab  for the treatment of high-grade glioma.
AB  - INTRODUCTION: Gliomas are highly vascular and rich in vascular endothelial growth
      factor (VEGF) that promotes angiogenesis. Bevacizumab is a monoclonal antibody
      against VEGF inhibiting angiogenesis by preventing receptor activation. Phase II
      clinical trials using bevacizumab in both newly diagnosed and recurrent high
      grade glioma (HGG) showed promising results. AREAS COVERED: This is a review of
      clinical trials investigating bevacizumab in newly diagnosed and recurrent HGGs
      with a focus on outcome results. A future perspective about the expected role of
      bevacizumab is given. Bevacizumab efficacy, safety and tolerability, the
      combination of radiation and bevacizumab as well as the use of bevacizumab to
      treat pseudoprogression are discussed. Further criteria of response evaluation
      needed to be adjusted in the age of anti-angiogenic therapy and this will be
      discussed. EXPERT OPINION: Bevacizumab has been shown to be safe and tolerable in
      HGG. In the recurrent disease setting, bevacizumab alone might be sufficient for
      a clinical benefit and is currently approved as a single agent for this
      indication. While clinical trials demonstrate a prolonged progression-free
      survival in bevacizumab-treated HGG, a benefit on OS has not been demonstrated
      yet. Bevacizumab has also been introduced into other settings in neuro-oncology
      including concurrent administration with re-irradiation for recurrent HGG.

PMID- 22663138
TI  - Nalfurafine hydrochloride  for the treatment of pruritus.
AB  - INTRODUCTION: Severe pruritus associated with end-stage renal disease is a
      particularly troublesome complication, because no effective treatment has been
      established. However, based on the findings of a recent randomized controlled
      trial, nalfurafine hydrochloride was officially approved in Japan for the
      treatment of resistant pruritus in hemodialysis patients. AREAS COVERED: This
      review is based upon a PubMed search and personal experience with nalfurafine
      hydrochloride. The pharmacokinetics and pharmacodynamics of nalfurafine
      hydrochloride are reviewed and its efficiency and potential adverse effects are
      discussed, mainly based on the findings of randomized controlled trials. EXPERT
      OPINION: A recent long-term open trial showed that the effect of nalfurafine
      hydrochloride was enhanced by continuous, long-term administration. It will be of
      future interest to investigate its effect on excoriations, lichen simplex,
      prurigo nodularis and acquired perforating dermatosis (all caused by uremic
      pruritus), because it targets both the skin and the central nervous system. In
      clinical practice, it should be kept in mind that basic skin care with emollients
      and other topical drugs is essential for stopping the itch-scratch cycle, and the
      resultant skin barrier dysfunction.

PMID- 22663139
TI  - A new approach to 1,4-oxazines and 1,4-oxazepines via base-promoted exo mode
      cyclization of alkynyl alcohols: mechanism and DFT studies.
AB  - A new approach was developed to synthesize 1,4-oxazine and 1,4-oxazepine
      derivatives without solvent and metal. Regioselective cyclization occurred to
      afford exclusively the exo-dig product, and stereochemistry was studied by
      circular dichroism and specific optical rotation techniques. The Grignard
      reaction is a key synthetic step to produce high diastereomeric compounds via
      Cram's rule and was well supported by DFT calculations. A hydroalkoxylation
      mechanism was proposed and supported by DFT calculations.

PMID- 22663141
TI  - Single-molecule force spectroscopy of selenium-containing amphiphilic block
      copolymer: toward disassembling the polymer micelles.
AB  - Selenium-containing polymers are a new type of responsive polymer material. Here,
      a selenium-containing amphiphilic block copolymer (PEG-PUSe-PEG) has been
      investigated using atomic force microscopy (AFM)-based single-molecule force
      spectroscopy (SMFS). The deviation between force-extension curves of PEG-PUSe-PEG
      in water and in DMSO is found to be related to the disassembly of the micellar
      structures in water. SMFS experiments on PEG-PUSeox-PEG suggest that the change
      from selenide to oxidized selenone contributes significantly to the change in
      amphiphilicity, without obviously influencing the single-chain elasticity.

PMID- 22663140
TI  - Adaptive leadership: a novel approach for family decision making.
AB  - Family members of intensive care unit (ICU) patients want to be involved in
      decision making, but they may not be best served by being placed in the position
      of having to solve problems for which they lack knowledge and skills. This case
      report presents an exemplar family meeting in the ICU led by a palliative care
      specialist, with discussion about the strategies used to improve the capacity of
      the family to make a decision consistent with the patient's goals. These
      strategies are presented through the lens of Adaptive Leadership.

PMID- 22663142
TI  - Modeling the absorption of weak electrolytes and acid gases with ionic liquids
      using the soft-SAFT approach.
AB  - In this work, the solubility of three common pollutants, SO(2), NH(3), and H(2)S,
      in ionic liquids (ILs) is studied using the soft-SAFT equation of state with
      relatively simple models. Three types of imidazolium ionic liquids with different
      anions are described in a transferable manner using the recently published
      molecular models (Andreu, J. S.; Vega, L. F. J. Phys. Chem. C 2007, 111, 16028;
      Llovell et al. J. Phys. Chem. B 2011, 115, 4387), whereas new models for SO(2),
      NH(3), and H(2)S are proposed here. Alkyl-imidazolium ionic liquids with the
      [PF(6)](-) and [BF(4)](-) anions are considered to be Lennard-Jones chainlike
      molecules with one associating site in each molecule describing the specific
      cation-anion interactions. Conversely, the cation and anion forming the
      imidazolium [Tf(2)N](-) ionic liquids are modeled as a single molecule with three
      associating sites, taking into account the delocalization of the anion electric
      charge due to the presence of oxygen groups surrounding the nitrogen of the
      anion. NH(3) is described with four associating sites: three sites of type H
      mimicking the hydrogen atoms and one site of type e representing the lone pair of
      electrons. H(2)S is modeled with three associating sites: two for the sites of
      type H for the hydrogen atoms and one site of type e for the electronegativity of
      the sulfur. SO(2) is modeled with two sites, representing the dipole moment of
      the molecule as an associative interaction. Soft-SAFT calculations with the three
      models for the pollutants provide very good agreement with the available phase
      equilibria, enthalpy of vaporization, and heat capacity experimental data. Then,
      binary mixtures of these compounds with imidazolium-based ionic liquids were
      calculated in an industrially relevant temperature range. Unlike association
      interactions between the ionic liquids and the pollutant gases have been
      explicitly accounted for using an advanced association scheme. A single
      temperature independent energy binary parameter is sufficient to describe every
      family of mixtures in good agreement with the available data in the literature.
      In addition, a vapor-liquid-liquid equilibrium (VLLE) region, never measured
      experimentally, has been identified for mixtures of hydrogen sulfide +
      imidazolium ionic liquids with the [PF(6)](-) anion at high H(2)S concentrations.
      This work illustrates that relatively simple models are able to capture the phase
      absorption diagram of different gases in ionic liquids, provided accurate models
      are available for the pure components as well as an accurate equation of state to
      model the behavior of complex systems.

PMID- 22663143
TI  - Can biosecurity be embedded into the culture of the life sciences?

PMID- 22663145
TI  - Diffuse amyloid deposition in thyroid gland: a cause for concern in familial
      Mediterranean fever.
AB  - Thyroid gland is among the many organs that could be infiltrated in systemic
      amyloidosis. However, diffuse infiltration of the thyroid gland secondary to
      systemic amyloidosis associated with Familial Mediterranean fever (FMF) is rare.
      Here, we present a 49-year-old woman diagnosed with FMF and systemic amyloidosis,
      who had a large goiter and multiple nodules that developed slowly through the
      years and was complicated by tracheal compression symptoms and a mild thyroid
      dysfunction. Multiple fine needle aspiration biopsies of the nodules and the
      thyroid parenchyma revealed amyloid deposits. We would like to point out that
      amyloidosis may have a significant impact on the thyroid gland and fine needle
      aspiration biopsy is a valuable tool for diagnosis.

PMID- 22663146
TI  - Theory of late-transition-metal alkyl and heteroatom bonding: analysis of Pt, Ru,
      Ir, and Rh complexes.
AB  - Density functional and correlated ab initio methods were used to calculate,
      compare, and analyze bonding interactions in late-transition-metal alkyl and
      heteroatom complexes (M-X). The complexes studied include: (DMPE)Pt(CH(3))(X)
      (DMPE = 1,2-bis(dimethylphosphino)ethane), Cp*Ru(PMe(3))(2)(X) (Cp* =
      pentamethylcyclopentadienyl), (DMPE)(2)Ru(H)(X), (Tp)(CO)Ru(Py)(X) (Tp =
      trispyrazolylborate), (PMe(3))(2)Rh(C(2)H(4))(X), and cis-(acac)(2)Ir(Py)(X)
      (acac = acetylacetonate). Seventeen X ligands were analyzed that include alkyl
      (CR(3)), amido (NR(2)), alkoxo (OR), and fluoride. Energy decomposition analysis
      of these M-X bonds revealed that orbital charge transfer stabilization provides a
      straightforward model for trends in bonding along the alkyl to heteroatom ligand
      series (X = CH(3), NH(2), OH, F). Pauli repulsion (exchange repulsion), which
      includes contributions from closed-shell d(pi)-p(pi) repulsion, generally
      decreases along the alkyl to heteroatom ligand series but depends on the exact M
      X complexes. It was also revealed that stabilizing electrostatic interactions
      generally decrease along this ligand series. Correlation between M-X and H-X bond
      dissociation energies is good with R(2) values between 0.7 and 0.9. This
      correlation exists because for both M-X and H-X bonds the orbital stabilization
      energies are a function of the orbital electronegativity of the X group. The
      greater than 1 slope when correlating M-X and H-X bond dissociation energies was
      traced back to differences in Pauli repulsion and electrostatic stabilization.

PMID- 22663147
TI  - Evaluation of key odorants in sauvignon blanc wines using three different
      methodologies.
AB  - In this study three different approaches were employed to identify key odorants
      in Sauvignon blanc wines. First, the concentrations of the odorants were compared
      to their respective aroma detection thresholds. The resulting odor activity
      values (OAV) were transformed into a normalized and weighted measure that allows
      the aroma profiles of different wines to be compared and the contribution of a
      single aroma in a complex mixture to be evaluated. Based on their OAV, 3
      mercaptohexanol and 3-mercaptohexyl acetate were the two most important aroma
      compounds in many Marlborough Sauvignon blanc wines. Due to limitations with the
      OAV approach, the study was extended to include aroma extract dilution analysis
      (AEDA), which revealed that beta-damascenone, together with the varietal thiols,
      esters, and higher alcohols, are key odorants in Sauvignon blanc wines. The final
      approach undertaken was aroma reconstitution and omission tests using a
      deodorized wine base and the creation of a model Marlborough Sauvignon blanc.
      Single compounds and groups of compounds were omitted from the model to study
      their impact on the sensory properties of the model wine. Reconstitution and
      omission confirmed that varietal thiols, esters, terpenes, and beta-damascenone
      are all important contributors to Sauvignon blanc aroma. The methoxypyrazines
      showed an important but relatively low impact in all three of the approaches
      undertaken in this study.

PMID- 22663144
TI  - Health effects research and regulation of diesel exhaust: an historical overview
      focused on lung cancer risk.
AB  - The mutagenicity of organic solvent extracts from diesel exhaust particulate
      (DEP), first noted more than 55 years ago, initiated an avalanche of diesel
      exhaust (DE) health effects research that now totals more than 6000 published
      studies. Despite an extensive body of results, scientific debate continues
      regarding the nature of the lung cancer risk posed by inhalation of occupational
      and environmental DE, with much of the debate focused on DEP. Decades of
      scientific scrutiny and increasingly stringent regulation have resulted in major
      advances in diesel engine technologies. The changed particulate matter (PM)
      emissions in "New Technology Diesel Exhaust (NTDE)" from today's modern low
      emission, advanced-technology on-road heavy-duty diesel engines now resemble the
      PM emissions in contemporary gasoline engine exhaust (GEE) and compressed natural
      gas engine exhaust more than those in the "traditional diesel exhaust" (TDE)
      characteristic of older diesel engines. Even with the continued publication of
      epidemiologic analyses of TDE-exposed populations, this database remains
      characterized by findings of small increased lung cancer risks and inconsistent
      evidence of exposure-response trends, both within occupational cohorts and across
      occupational groups considered to have markedly different exposures (e.g.
      truckers versus railroad shopworkers versus underground miners). The recently
      published National Institute for Occupational Safety and Health (NIOSH)-National
      Cancer Institute (NCI) epidemiologic studies of miners provide some of the
      strongest findings to date regarding a DE-lung cancer association, but some
      inconsistent exposure-response findings and possible effects of bias and exposure
      misclassification raise questions regarding their interpretation. Laboratory
      animal studies are negative for lung tumors in all species, except for rats under
      lifetime TDE-exposure conditions with durations and concentrations that lead to
      "lung overload." The species specificity of the rat lung response to overload,
      and its occurrence with other particle types, is now well-understood. It is thus
      generally accepted that the rat bioassay for inhaled particles under conditions
      of lung overload is not predictive of human lung cancer hazard. Overall, despite
      an abundance of epidemiologic and experimental data, there remain questions as to
      whether TDE exposure causes increased lung cancers in humans. An abundance of
      emissions characterization data, as well as preliminary toxicological data,
      support NTDE as being toxicologically distinct from TDE. Currently, neither
      epidemiologic data nor animal bioassay data yet exist that directly bear on NTDE
      carcinogenic potential. A chronic bioassay of NTDE currently in progress will
      provide data on whether NTDE poses a carcinogenic hazard, but based on the
      significant reductions in PM mass emissions and the major changes in PM
      composition, it has been hypothesized that NTDE has a low carcinogenic potential.
      When the International Agency for Research on Cancer (IARC) reevaluates DE (along
      with GEE and nitroarenes) in June 2012, it will be the first authoritative body
      to assess DE carcinogenic health hazards since the emergence of NTDE and the
      accumulation of data differentiating NTDE from TDE.

PMID- 22663148
TI  - High-power coherent microwave emission from magnetic tunnel junction nano
      oscillators with perpendicular anisotropy.
AB  - The excitation of the steady-state precessions of magnetization opens a new way
      for nanoscale microwave oscillators by exploiting the transfer of spin angular
      momentum from a spin-polarized current to a ferromagnet, referred to as spin
      transfer nano-oscillators (STNOs). For STNOs to be practical, however, their
      relatively low output power and their relatively large line width must be
      improved. Here we demonstrate that microwave signals with maximum measured power
      of 0.28 MUW and simultaneously narrow line width of 25 MHz can be generated from
      CoFeB-MgO-based magnetic tunnel junctions having an in-plane magnetized reference
      layer and a free layer with strong perpendicular anisotropy. Moreover, the
      generation efficiency is substantially higher than previously reported STNOs. The
      results will be of importance for the design of nanoscale alternatives to
      traditional silicon oscillators used in radio frequency integrated circuits.

PMID- 22663149
TI  - Mechanistic analysis of the contributions of DNA and protein damage to radiation
      induced cell death.
AB  - Protein oxidation can contribute to radiation-induced cell death by two
      mechanisms: (1) by reducing the fidelity of DNA repair, and (2) by decreasing
      cell viability directly. Previously, we explored the first mechanism by
      developing a mathematical model and applying it to data on  Deinococcus
      radiodurans . Here we extend the model to both mechanisms, and analyze a recently
      published data set of protein carbonylation and cell survival in  D. radiodurans 
      and  Escherichia coli  exposed to gamma and ultraviolet radiation. Our results
      suggest that similar cell survival curves can be produced by very different
      mechanisms. For example, wild-type  E. coli  and DNA double-strand break (DSB)
      repair-deficient recA-  D. radiodurans  succumb to radiation doses of similar
      magnitude, but for different reasons: wild-type  E. coli  proteins are easily
      oxidized, causing cell death even at low levels of DNA damage, whereas proteins
      in recA-  D. radiodurans  are well protected from oxidation, but DSBs are not
      repaired correctly even when most proteins are intact. Radioresistant  E. coli 
      mutants survive higher radiation doses than the wild-type because of superior
      protection of cellular proteins from radiogenic oxidation. In contrast, wild-type
      D. radiodurans  is much more radioresistant than the recA- mutant because of
      superior DSB repair, whereas protein protection in both strains is similar. With
      further development, the modeling approach presented here can also quantify the
      causes of radiation-induced cell death in other organisms. Enhanced understanding
      of these causes can stimulate research on novel radioprotection strategies.

PMID- 22663151
TI  - Neutral mononuclear, dinuclear, tetranuclear d7/d10 metal complexes containing
      bis-pyrazole/pyridine ligands supported by 2,6-bis(3-pyrazolyl)pyridine:
      synthesis, structure, spectra, and catalytic activity.
AB  - A series of novel bis-pyrazole/pyridine complexes, [Zn(2)(HL(1))(2)(MU(2)
      SO(4))](2).EtOH.H(2)O (1), [Co(2)(HL(1))(2)(MU(2)-SO(4))](2).2DMF.6H(2)O (2),
      [Zn(4)(HL(1))(4)(MU(4)-SO(4))][OH](2) (3), [Zn(2)(HL(2))(2)(MU(2)-SO(4))].2H(2)O
      (4), [Zn(H(2)L(2))(H(2)O)(2)](SO(4)).0.87H(2)O (5) (H(2)L(1) = 2,6-di-(5-phenyl
      1H-pyrazol-3-yl)pyridine, H(2)L(2) = 2,6-di-(5-methyl-1H-pyrazol-3-yl)pyridine),
      were synthesized hydrothermally from the self-assembly of Zn(II) or Co(II) with
      different types of bipyrazolyl/pyridine derivative ligands. All the complexes
      were characterized by elemental analysis, IR and UV-vis spectroscopy, powder X
      ray diffraction (PXRD), and single-crystal X-ray diffraction. Structural analyses
      revealed that metal atoms (Zn and Co) in complexes 1-5 are five-coordination
      modes, forming slightly distorted trigonal bipyramidal geometries. In complexes 1
      3, H(2)L(1) ligand connected the two metal centers via the tetradentate fashion,
      and the same form of connection was found in complex 4 with H(2)L(2) ligand.
      While in complex 5, H(2)L(2) only connected with one metal center via the
      tridentate fashion, which was different from those in complexes 1-4.
      Additionally, there are abundant hydrogen bonding interactions in complexes 1-4.
      Interestingly, for hydrogen bonding connecting fashions being different, the
      molecules for the complexes 1 and 4 are held together by the hydrogen bond to
      form a 1D supramolecular structure, whereas complexes 2 and 3 are a hydrogen
      bonded dimer. In addition, quantum chemical calculations for 1, 3, and 4, thermal
      behaviors and photoluminescent properties for 1 and 3-5 were performed and
      discussed in detail. In the mean time, we found that these complexes had
      potential catalytic activity for the oxidation reaction of cyclohexane.

PMID- 22663150
TI  - Experimental radiation-induced heart disease: past, present, and future.
AB  - Radiation-induced heart disease (RIHD) is a serious side effect of radiotherapy
      for intrathoracic and chest wall tumors. The threshold dose for development of
      clinically significant RIHD is believed to be lower than previously assumed.
      Therefore, research into mechanisms of RIHD has gained substantial momentum. RIHD
      becomes clinically apparent ten to fifteen years after radiation exposure.
      Chronic manifestations of RIHD include accelerated atherosclerosis,
      cardiomyopathy, and valve abnormalities. Reducing exposure of the heart during
      radiotherapy is the only known method of preventing RIHD, and there are no
      approaches to reverse RIHD once it occurs. We use a combination of
      pharmacological and genetic animal models to determine biological mechanisms of
      RIHD. Major technological advances in small animal research have made this type
      of study more valuable. The long-term goal of this work is to identify targets
      for intervention in RIHD, thereby enhancing the efficacy and safety of thoracic
      radiotherapy.

PMID- 22663152
TI  - Approaches to the construction of substituted 4-amino-1H-pyrrol-2(5H)-ones.
AB  - Fully substituted 4-aminopyrrolones are easily accessed via simple routes
      starting from imines, ketones, or alpha-bromophenyl acetonitriles. Imines were
      reacted with KCN/NH(4)Cl in aqueous ethanol to produce alpha-arylamino benzyl
      cyanides. On the other hand, ketones were transformed to the desired alpha-amino
      nitriles using a modified Strecker reaction. Then, alpha-amino nitrile precursors
      were allowed to react with a suitable acyl halide to produce the corresponding
      amides. Further treatment of these amides with ethanolic KOH converted them to
      highly substituted 4-amino-1H-pyrrol-2(5H)-one derivatives in moderate to
      excellent yields.

PMID- 22663154
TI  - Effectiveness of green infrastructure for improvement of air quality in urban
      street canyons.
AB  - Street-level concentrations of nitrogen dioxide (NO(2)) and particulate matter
      (PM) exceed public health standards in many cities, causing increased mortality
      and morbidity. Concentrations can be reduced by controlling emissions, increasing
      dispersion, or increasing deposition rates, but little attention has been paid to
      the latter as a pollution control method. Both NO(2) and PM are deposited onto
      surfaces at rates that vary according to the nature of the surface; deposition
      rates to vegetation are much higher than those to hard, built surfaces.
      Previously, city-scale studies have suggested that deposition to vegetation can
      make a very modest improvement (<5%) to urban air quality. However, few studies
      take full account of the interplay between urban form and vegetation,
      specifically the enhanced residence time of air in street canyons. This study
      shows that increasing deposition by the planting of vegetation in street canyons
      can reduce street-level concentrations in those canyons by as much as 40% for
      NO(2) and 60% for PM. Substantial street-level air quality improvements can be
      gained through action at the scale of a single street canyon or across city-sized
      areas of canyons. Moreover, vegetation will continue to offer benefits in the
      reduction of pollution even if the traffic source is removed from city centers.
      Thus, judicious use of vegetation can create an efficient urban pollutant filter,
      yielding rapid and sustained improvements in street-level air quality in dense
      urban areas.

PMID- 22663153
TI  - Assessment of relative brain-skull motion in quasistatic circumstances by
      magnetic resonance imaging.
AB  - Brain-skull relative motion plays a pivotal role in the etiology of traumatic
      brain injury (TBI). The present study aims to assess brain-skull relative motion
      in quasistatic circumstances, and to correlate cortical regions with high motion
      amplitudes with sites prone to cerebral contusions. The study includes 30 healthy
      volunteers scanned using a clinical 3-T MR scanner in four different head
      positions. Through image processing and 3D model registration, pairwise
      comparisons were performed to calculate the brain shift between sagittal and
      coronal head positional change. Next, local brain deformation was evaluated by
      comparison between cortical and ventricular amplitudes. Finally, the influence of
      age, sex, and skull geometry on the cortical and ventricular motion was
      investigated. The results describe complex brain shift patterns, with high
      regional and inter-individual variations, outweighing age and sex patterns.
      Regions with maximum motion amplitudes were identified at the inferolateral
      aspects of the frontal and temporal lobes, congruent with predilection sites for
      contusions. No significant influences of age and sex on the cortical shift
      amplitudes were detected. The 3D cortical deviations varied from -7.86 mm to
      +5.71 mm for the sagittal head movement, and from -11.46 mm to +7.30 mm for head
      movement in the coronal plane, for a 95% confidence interval. The present study
      contributes to a better understanding of the mechanopathogenesis of
      frontotemporal contusions, and is useful for the optimization of finite-element
      head models and neurosurgical navigation procedures. Moreover, our results prove
      that in vivo MRI allows for accurate assessment of brain-skull relative motion in
      quasistatic conditions.

PMID- 22663155
TI  - Gambogic acid deactivates cytosolic and mitochondrial thioredoxins by covalent
      binding to the functional domain.
AB  - Gambogic acid (1) is a cytotoxic caged xanthone derived from the resin of
      Garcinia hanburyi. Compound 1 selectively induces apoptosis in cancer cells, at
      least partially, by targeting the stress response to reactive oxygen species
      (ROS). However, the molecular mechanism of ROS toxicity stimulated by 1 remains
      poorly understood. In this study, mass spectrometric and biochemical
      pharmacological approaches were used that resulted in the identification of both
      cytosolic thioredoxin (TRX-1) and mitochondrial thioredoxin (TRX-2) as the
      molecular targets of 1. The results obtained showed that 1 deactivates TRX-1/2
      proteins by covalent binding to the active cysteine residues in the functional
      domain via Michael addition reactions. Since both TRX-1 and TRX-2 play key roles
      in regulating the redox signaling of cancer cells, the present findings may shed
      light on the relationship between protein binding and cellular ROS accumulation
      induced by 1. This provides support for the current clinical trials of gambogic
      acid (1) being conducted alone or in combination with other agents that appear to
      increase ROS generation in order to selectively kill cancer cells.

PMID- 22663156
TI  - Can older adults accurately judge their learning of emotional information?
AB  - Prior research suggests that older adults judge their learning as well as young
      adults, but given age-related differences in the processing of emotional
      materials, older adults may show deficits in their judgment accuracy when they
      study emotionally charged words. In 2 experiments, we evaluated this possibility
      by having young and older adults study negative, positive, and neutral words.
      They made a judgment of learning (JOL) after studying each word and then later
      had a free recall test. In Experiment 1, young and older adults' JOLs were
      sensitive to negative words (higher JOLs for negative than neutral words). By
      contrast, whereas young adults' JOLs were sensitive to positive emotion (higher
      for positive than neutral words), older adults' JOLs were insensitive. In
      Experiment 2, we replicated this age-related deficit in sensitivity to positive
      emotion, as well as evaluated possible explanations for it. As important, in both
      experiments, JOLs were plotted as a function of input serial position, and the
      shape of these curves were not influenced by emotional valence or age group.
      Taken together, these results indicate that healthy aging largely leaves
      judgments of learning intact for negatively charged words.

PMID- 22663157
TI  - Information search and decision making: effects of age and complexity on strategy
      use.
AB  - The impact of task complexity on information search strategy and decision quality
      was examined in a sample of 135 young, middle-aged, and older adults. We were
      particularly interested in the competing roles of fluid cognitive ability and
      domain knowledge and experience, with the former being a negative influence and
      the latter being a positive influence on older adults' performance. Participants
      utilized 2 decision matrices, which varied in complexity, regarding a consumer
      purchase. Using process tracing software and an algorithm developed to assess
      decision strategy, we recorded search behavior, strategy selection, and final
      decision. Contrary to expectations, older adults were not more likely than the
      younger age groups to engage in information-minimizing search behaviors in
      response to increases in task complexity. Similarly, adults of all ages used
      comparable decision strategies and adapted their strategies to the demands of the
      task. We also examined decision outcomes in relation to participants'
      preferences. Overall, it seems that older adults utilize simpler sets of
      information primarily reflecting the most valued attributes in making their
      choice. The results of this study suggest that older adults are adaptive in their
      approach to decision making and that this ability may benefit from accrued
      knowledge and experience.

PMID- 22663158
TI  - Metacognitive monitoring in visuospatial working memory.
AB  - Research within the domain of spatial working memory has not conclusively
      determined whether age differences exist. Under some conditions, age-equivalence
      has been demonstrated for location information. Under other conditions, age
      equivalence has been demonstrated for identity information. In three experiments,
      we examined identity memory, location memory, and their combination in a
      visuospatial working memory (VSWM) paradigm. Older and younger adults were
      compared. In addition, we examined metacognitive processes associated with each
      VSWM component. Results suggest an overall age-deficit in VSWM. Our results also
      suggest that location information may be less effortfully processed as compared
      to identity information. With regarding to metacognitive monitoring, we found age
      equivalence for identity prediction accuracy and an age-related deficit in
      prediction accuracy for location information. The present study is the first to
      demonstrate both age-deficits and age-equivalence in metacognitive prediction
      accuracy within a working memory paradigm.

PMID- 22663159
TI  - Four events of host switching in Aspidoderidae (Nematoda) involve convergent
      lineages of mammals.
AB  - The Great American Interchange resulted in the mixing of faunistic groups with
      different origins and evolutionary trajectories that underwent rapid
      diversification in North and South America. As a result, groups of animals of
      recent arrival converged into similar habits and formed ecological guilds with
      some of the endemics. We present a reconstruction of the evolutionary events in
      Aspidoderidae, a family of nematodes that infect mammals that are part of this
      interchange, i.e., dasypodids, opossums, and sigmodontine, geomyid, and
      hystricognath rodents. By treating hosts as discrete states of character and
      using parsimony and Bayesian inferences to optimize these traits into the
      phylogeny of Aspidoderidae, we reconstructed Dasypodidae (armadillos) as the
      synapomorphic host for the family. In addition, 4 events of host switching were
      detected. One consisted of the switch from dasypodids to hystricognath rodents,
      and subsequently to geomyid rodents. The remaining set of events consisted of a
      switch from dasypodids to didelphid marsupials and then to sigmodontine rodents.
      The reconstruction of the ancestral distribution suggests 3 events of dispersal
      into the Nearctic. Two of these invasions would suggest that 2 different lineages
      of dasypodid parasites entered the Northern Hemisphere at different times, which
      is consistent with the presence of 2 lineages of armadillos in Mexico.

PMID- 22663160
TI  - Bendamustine  for treatment of chronic lymphocytic leukemia.
AB  - INTRODUCTION: Chronic lymphocytic leukemia (CLL) often has an extended disease
      course. With a median age at diagnosis of 72 years, newer treatment options with
      less toxicity than standard nucleoside analogue-based regimens are needed.
      Historically, few therapy options are available once CLL has become refractory to
      nucleoside analogues. Bendamustine has emerged as a feasible therapy for older
      and less fit CLL patients, with clinical efficacy in previously untreated and
      refractory CLL. AREAS COVERED: This paper reviews several of the pivotal clinical
      trials that established the clinical activity of bendamustine in previously
      untreated and relapsed/refractory CLL. The toxicity profile of bendamustine,
      primarily myelosuppression and infections, is reviewed and compared across
      different CLL populations. A review of the clinical data focuses on potential
      explanations for differences in response rates and duration of remission reported
      across studies and how this may impact the development of therapies for CLL.
      EXPERT OPINION: Bendamustine is a valuable new agent for the management of CLL.
      Ongoing clinical trials are comparing bendamustine with standard CLL regimens in
      untreated disease, and investigating bendamustine combinations with novel
      targeted therapies and monoclonal antibodies. These studies will help to define
      the optimal role for bendamustine in CLL management.

PMID- 22663161
TI  - Rosmarinic acid content in antidiabetic aqueous extract of Ocimum canum sims
      grown in Ghana.
AB  - Rosmarinic acid (RA) is an important antioxidant polyphenol that is found in a
      variety of spices and herbs, including Ocimum canum Sims (locally called eme or
      akokobesa in Ghana). Aqueous extracts from the leaves of O. canum are used as an
      antidiabetic herbal medicine in Ghana. Analytical thin-layer chromatography was
      used to examine the composition of the polyphenols in leaf extracts. The
      polyphenol content in the aqueous and methanol extracts from the leaf, as
      determined by the Folin-Ciocalteu method, were 314 and 315 mg gallic acid
      equivalent/g leaf sample, respectively. The total flavonoid concentration as
      determined by the aluminum(III) chloride method was 135 mg catechin equivalent/g
      leaf sample. High-performance liquid chromatography coupled to an electrospray
      Quadrupole time-of-flight mass spectrometer was also used to determine the
      polyphenol fingerprint profile in the leaf extracts of O. canum. Although the
      average RA concentration in the O. canum leaf extracts from Ghana was 1.69 mg/g
      dry weight (reported values range from 0.01 to 99.62 mg/g dry weight), this
      polyphenol was still a prominent peak in addition to caffeic acid derivatives.

PMID- 22663162
TI  - Molecular mechanism of specific ion interactions between alkali cations and
      acetate anion in aqueous solution: a molecular dynamics study.
AB  - Specific ion interactions between alkali cations (i.e., Li(+), Na(+), and K(+))
      and an acetate anion in aqueous solution were studied using molecular dynamics
      simulation techniques and polarizable potential models. The ions-acetate systems
      were used as a model for understanding the interactions between ions and protein
      surfaces. We computed free energy profiles for different ion pairs using
      constrained mean force methods. Upon analyzing the computed free energy profiles
      for the Na(+)/K(+)-acetate ion-pairs, we observed a deeper contact ion minimum
      and also a larger association constant for the Na(+)-acetate pair as compared to
      the corresponding K(+)-acetate pair. These observations help to demonstrate the
      preferential binding of Na(+) over K(+) to protein surfaces. We also applied
      various rate theories to study the kinetics of ion pair interconversion.

PMID- 22663163
TI  - Atomic structure of ABC rhombohedral stacked trilayer graphene.
AB  - We distinguish between Bernal and rhombohedral stacked trilayer graphene using
      aberration-corrected high-resolution transmission electron microscopy. By using a
      monochromator to reduce chromatic aberration effects, angstrom resolution can be
      achieved at an accelerating voltage of 80 kV, which enables the atomic structure
      of ABC rhombohedral trilayer graphene to be unambiguously resolved. Our images of
      ABC rhombohedral trilayer graphene provide a clear signature for its
      identification. Few-layer graphene interfaces with ABC:BC:BCAB structure have
      also been studied, and we have determined the stacking sequence of each graphene
      layer and consequently the 3D structure. These results confirm that CVD-grown few
      layer graphene can adopt an ABC rhombohedral stacking.

PMID- 22663164
TI  - Trends and weekly and seasonal cycles in the rate of errors in the clinical
      management of hospitalized patients.
AB  - Studies on the rate of adverse events in hospitalized patients seldom examine
      temporal patterns. This study presents evidence of both weekly and annual cycles.
      The study is based on a large and diverse data set, with nearly 5 yrs of data
      from a voluntary staff-incident reporting system of a large public health care
      provider in rural southeastern Australia. The data of 63 health care facilities
      were included, ranging from large non-metropolitan hospitals to small community
      and aged health care facilities. Poisson regression incorporating an observation
      driven autoregressive effect using the GLARMA framework was used to explain daily
      error counts with respect to long-term trend and weekly and annual effects, with
      procedural volume as an offset. The annual pattern was modeled using a first
      order sinusoidal effect. The rate of errors reported demonstrated an increasing
      annual trend of 13.4% (95% confidence interval [CI] 10.6% to 16.3%); however,
      this trend was only significant for errors of minor or no harm to the patient. A
      strong "weekend effect" was observed. The incident rate ratio for the weekend
      versus weekdays was 2.74 (95% CI 2.55 to 2.93). The weekly pattern was consistent
      for incidents of all levels of severity, but it was more pronounced for less
      severe incidents. There was an annual cycle in the rate of incidents, the number
      of incidents peaking in October, on the 282 nd day of the year (spring in
      Australia), with an incident rate ratio 1.09 (95% CI 1.05 to 1.14) compared to
      the annual mean. There was no so-called "killing season" or "July effect," as the
      peak in incident rate was not related to the commencement of work by new medical
      school graduates. The major finding of this study is the rate of adverse events
      is greater on weekends and during spring. The annual pattern appears to be
      unrelated to the commencement of new graduates and potentially results from
      seasonal variation in the case mix of patients or the health of the medical
      workforce that alters health care performance. These mechanisms will need to be
      elucidated with further research.

PMID- 22663166
TI  - A comparison of partner notification effectiveness in African-, Caribbean-, and
      United States-born HIV-infected Blacks in New York City.
AB  - HIV disproportionately affects blacks more than other groups in New York City
      (NYC) as well as nationally. Partner Services (PS) are a proven way to interrupt
      HIV transmission. In NYC, PS outcomes are worse among blacks compared to other
      race/ethnic groups. We compared PS outcomes by country of birth to identify
      opportunities for improved PS effectiveness. We assessed number of sex and needle
      sharing partners elicited, notified, and HIV tested, as well as number of newly
      identified HIV cases and number of interviews needed to identify a new HIV case.
      Between July 2006 and December 2008, 1049 African Americans, 285 Caribbean-born
      blacks, and 168 African-born blacks were interviewed for HIV Partner Services.
      African Americans, Caribbean-born blacks, and African-born blacks had average age
      of 38, 37, and 43 years and 10.0%, 0.4%, and 0.6% reported intravenous drug use,
      respectively. All groups had a high proportion of cases with an AIDS-defining CD4
      count at HIV diagnosis (30.8%, 34.5%, and 47.9% for African Americans, Africans,
      and Caribbeans, respectively). The number needed to interview to find one newly
      diagnosed HIV case was high for all groups (66, 57, and 56 among African
      Americans, Africans, and Caribbeans, respectively), indicating all had similarly
      low rates of new HIV case identification. NYC blacks and their partners are
      benefiting from current Partner Services outreach as PS did identify new HIV
      cases among partners from all 3 groups. However, further work is needed to
      improve HIV case finding from Partner Services in these groups, and additional
      measures to promote early diagnosis are needed.

PMID- 22663165
TI  - The pleasure principle: the effect of perceived pleasure loss associated with
      condoms on unprotected anal intercourse among immigrant Latino men who have sex
      with men.
AB  - Sexual pleasure has been identified as an important consideration in decision
      making surrounding condom use. We examined the impact of perceived pleasure loss
      associated with condom use on recent history of insertive and receptive
      unprotected anal intercourse (UAI) among Latino men who have sex with men (MSM)
      living in the United States. A total of 482 Dominican, Colombian, and Brazilian
      immigrant MSM were surveyed regarding sexual attitudes and practices via computer
      assisted self-interviewing technology with audio enhancement (ACASI).
      Participants rated the pleasure they derived from protected and unprotected anal
      intercourse in each position (insertive and receptive) and also reported their
      HIV status, relationship status, and recent sexual history. Men who had engaged
      in both positions, with and without condoms (n=268), perceived a greater pleasure
      loss associated with condoms during anal intercourse in the insertive versus
      receptive position. Logistic regression analyses controlling for HIV status,
      relationship status, and age revealed that men who perceived greater pleasure
      loss from condoms were more likely to have engaged in UAI over the past 3 months
      (n[insertive]=297; n[receptive]=284). Findings indicate that the pleasure loss
      associated with condoms may be a key deterrent for their use in either sex
      position among Latino MSM. Therefore, pleasure needs to be prioritized in the
      development of condoms and other sexual safety measures as well as in the
      promotion of their use.

PMID- 22663167
TI  - Microsponges: a futuristic approach for oral drug delivery.
AB  - INTRODUCTION: Microparticulate drug delivery systems have, due to their
      advantages, guided researchers across the globe to explore them as drug carriers.
      This has, sequentially, led to the development of microsponges in 1988. These
      porous microspheres were exclusively designed for chronotherapeutic topical drug
      delivery but attempts to utilize them for oral, pulmonary and parenteral drug
      delivery were also made. Researchers have extensively studied their properties
      and characteristics affecting the drug release and loading. Various advances were
      made with this carrier particle resulting in the development of various novel
      development techniques and carrier particles. AREAS COVERED: This review deals
      with the considerations of the drug material to be entrapped in microsponges,
      pharmaceutical considerations for fabrication of microsponges, their potential
      for oral drug delivery, clinical perspectives and also provides an insight on the
      recent advances made in this field and future prospect. EXPERT OPINION: Clinical
      studies show that these carriers can increase drug efficacy. Due to their
      potential advantages over other carrier particles, microsponges form a
      prospective platform for the oral delivery of pharmaceuticals and
      biopharmaceuticals. Although these carriers have several advantages, they too
      possess some drawbacks which limit their commercialization for oral application.

PMID- 22663168
TI  - Development of a conceptual model of adherence to oral anticoagulants to reduce
      risk of stroke in patients with atrial fibrillation.
AB  - BACKGROUND: Oral anticoagulant (OA) medication is the recommended therapy for
      reducing the risk of thromboembolic complications in patients with atrial
      fibrillation (AF), and warfarin is the medication most frequently used. However,
      nonadherence associated with OA medications may lead to considerable health
      risks. A conceptual model of OA medication adherence in patients with AF could
      clarify factors affecting adherence, thereby assisting in the development and
      structuring of adherence-promotion programs. To our knowledge, such a model,
      driven by information obtained directly from patients, has never been developed.
      OBJECTIVE: To develop a conceptual model of adherence to OA medication based on a
      literature review and patient feedback via qualitative research among patients
      with AF. METHODS: A literature search was conducted of English-language articles
      published between the years 2005 and 2010 that related to factors affecting OA
      medication adherence, excluding articles pertaining to AF associated with
      mechanical heart valve replacement. To expand on the literature review findings,
      4 focus groups totaling 38 participants aged 60 years or older, diagnosed with
      nonvalvular AF, and currently taking any OA medication were conducted in 2011.
      Participants completed the Modified Morisky Scale (MMS), with subscales measuring
      motivation and knowledge, and were asked about daily processes and behaviors
      related to taking OA medication. The identification of focus group themes was
      based on the frequency of participant report and endorsement; themes were
      spontaneously mentioned or supported by at least 2 people in each of at least 3
      focus groups. Model concepts, based on focus group themes and factors identified
      in the literature review, were determined by the consensus of 3 authors. RESULTS:
      181 publications were identified; 30 were selected for full-text review. The
      focus group participants had a mean age of 69.9 years. Most participants reported
      a diagnosis of hypertension (86.8%, n=33), high cholesterol (50.0%, n=19), heart
      disease or chronic heart failure (31.6%, n=12), or diabetes (28.9%, n=11). Most
      (89.5%, n=34) were taking warfarin. About one-half (52.6%, n=20) had been taking
      an OA medication for less than 5 years. On the MMS, 78.9% of participants
      reported high levels of motivation, and 100% reported high levels of knowledge.
      Four concepts emerged from the focus groups and were supported by the literature
      for inclusion in the model: (a) knowledge base of the disease and continued
      reinforcement (i.e., health care professional reinforcement); (b) short-term and
      long-term motivation (e.g., avoidance of negative health consequences); (c)
      personalized system, habit formation, and system adaptation (e.g., developing a
      routine or external reminders); and (d) self-efficacy loop (i.e., the
      personalized system and its adaptability are reinforced as patients become more
      consistent, confident, and adherent). The literature review also suggested other
      factors that may also affect patient adherence (e.g., demographic, psychosocial,
      cognitive). CONCLUSION: Adherence in patients with AF is complex and involves
      multiple factors, some specific to each individual and others more general. This
      model identifies an adherence process that can guide opportunities for effective
      interventions, such as educational and behavioral programs targeted at these
      processes, to improve patient adherence to OA medication.

PMID- 22663169
TI  - All-cause and potentially disease-related health care costs associated with
      venous thromboembolism in commercial, Medicare, and Medicaid beneficiaries.
AB  - BACKGROUND: Patients with venous thromboembolism (VTE) are at increased risk of
      developing recurrent VTE and post-thrombotic syndrome (PTS), a complication of
      deep vein thrombosis (DVT) characterized by venous reflux and residual venous
      obstruction that may manifest as chronic pain and swelling. Therefore,
      formulary/policy decision makers should understand the clinical and economic
      consequences associated with VTE. OBJECTIVES: To describe the real-world clinical
      complications, such as recurrent VTE and PTS, associated with VTE and quantify
      the incremental direct all-cause and potentially disease-related health care
      costs associated with VTE. METHODS: Health insurance claims between January 2004
      and December 2008 from the Ingenix Impact database were used. Adult patients with
      an initial VTE diagnosis (index DVT, pulmonary embolism [PE], or both) with at
      least 12 months of enrollment prior to the index VTE were matched 1:1 with
      comparison patients without VTE. Matching criteria included demographic factors,
      baseline health care costs, and diagnoses of VTE risk factors such as multiple
      traumas, malignant cancer, or major surgery. Each patient's observation period
      began on the date of the index VTE, or corresponding study index date for
      comparison cases, and ended on the earliest of 1 year after the study index date,
      the health plan disenrollment date, or December 31, 2008. The proportions of
      patients with (a) recurrent hospital-documented VTE, defined as an inpatient
      episode with a diagnosis of VTE in any claim field; (b) PTS; and (c) other
      potentially disease-related diagnoses (thrombocytopenia, superficial venous
      thrombosis, venous ulcer, pulmonary hypertension, stasis dermatitis, and venous
      insufficiency) were calculated. Health care costs were defined as standardized
      net provider payments after subtraction of member cost-sharing amounts. All-cause
      incremental health care costs and disease-related costs, defined as provider
      payments for hospitalization or outpatient claims with a primary or secondary
      diagnosis of VTE, PTS, or any of the potentially disease-related diagnoses, were
      computed. Costs were calculated per patient per year (PPPY) by weighting each
      patient's total cost for up to 1 year post-index by the length of follow-up.
      RESULTS: The matched VTE and no-VTE cohorts included 16,969 subjects in each
      group. The index VTE event was DVT, PE, or both in 12,711, 2,473, and 1,785
      patients, respectively. In the VTE cohort, the risks of recurrent VTE and PTS
      during the follow-up period (mean [SD] observation of 271.7 [121.6] days) were
      3.6% and 7.1%, respectively. Patients with VTE had significantly higher average
      PPPY all-cause costs compared with the no-VTE patients (mean [SD] $33,531
      [$70,393] vs. $17,590 [$42,011]; cost difference = $15,941, 95% CI = $14,819
      $17,012). Corresponding potentially disease-related health care costs PPPY were
      also significantly higher for the VTE group (mean [SD] $3,141 [$17,055] vs. $228
      [$3,221]; cost difference = $2,913, 95% CI = $2,693-$3,157) and represented 18.3%
      (i.e., $2,913 of $15,941) of the all-cause cost difference between the 2 groups.
      CONCLUSIONS: In this large matched-cohort study, VTE was associated with a 3.6%
      risk of hospital-documented recurrence and a 7.1% risk of PTS up to 1 year after
      index VTE. Potentially disease-related costs represented approximately one-fifth
      of the incremental all-cause costs associated with VTE.

PMID- 22663170
TI  - Clinical and cost efficacy of advanced wound care matrices for venous ulcers.
AB  - BACKGROUND: In the United States, venous leg ulcers (VLUs) are commonly
      associated with substantial disability, impaired quality of life, and high
      economic costs. Compression therapy, which has remained the standard care for
      VLUs over several decades, is often insufficient to heal VLUs in a timely manner.
      VLU-related treatment costs are directly related to time to achieve complete
      wound closure. Advanced wound care matrices (AWCMs) developed to stimulate wound
      healing may reduce VLU-related costs associated with delayed healing. Randomized
      controlled trials (RCTs) have evaluated the wound-healing efficacy of several
      AWCMs in patients with VLUs. However, comparisons of products' clinical and cost
      efficacy, which may guide clinical and formulary determinations, are lacking.
      OBJECTIVE: To evaluate, in terms of number needed to treat (NNT), the comparative
      clinical and cost efficacy of targeted AWCMs as adjuncts to compression therapy
      for the treatment of chronic VLUs from the U.S. health care system (payer)
      perspective. METHODS: A review of published articles (from the earliest available
      Medline publication date to June 1, 2011) identified RCTs evaluating complete
      wound closure rates for up to 24 weeks in patients with VLUs treated with
      targeted AWCMs (Apligraf, Oasis, or Talymed) plus compression therapy compared
      with compression therapy alone. The most favorable estimates of product efficacy
      (i.e., those that were statistically significant compared with compression
      therapy) were used. These included statistically adjusted results for Apligraf as
      reported in the product insert and the biweekly application for Talymed. Based on
      the reported efficacy of targeted AWCMs, we calculated the NNT to achieve 1
      additional treatment success (i.e., complete wound closure) over that which was
      achieved with standard therapy alone; 95% CIs were estimated using the Wilson
      score method proposed by Newcombe. Cost efficacy, defined as the incremental cost
      per additional successfully treated patient, was then calculated by multiplying
      the NNT associated with each treatment by the product acquisition cost per
      treated VLU episode. RESULTS: One study for each of 3 targeted AWCMs (Apligraf
      [n=130 treatment, n=110 control]; Oasis Wound Matrix [n=62 treatment, n=58
      control]; and Talymed [n=22 treatment, n=20 control]) met inclusion criteria.
      Study designs and wound characteristics varied. Average VLU sizes were 1 cm2, 10
      12 cm2, and 10-13 cm2 in the studies of Apligraf, Oasis, and Talymed,
      respectively. Ulcer duration exceeded 12 months for 50% of patients in the
      Apligraf study and was at least 7 months for 47% of patients in the Oasis study;
      patients with ulcers exceeding 6 months were excluded from the study of Talymed.
      Length of follow-up was 24 weeks for Apligraf, 12 weeks for Oasis, and 20 weeks
      for Talymed. NNT point estimates of clinical efficacy were 2 for Talymed, 5 for
      Oasis, and 6 for Apligraf; 95% CIs ranged from 2 to 8 for Talymed, 3 to 24 for
      Apligraf, and 3 to 39 for Oasis. Incremental costs (95% CIs) per additional
      successfully treated patient were $1,600 ($1,600-$6,400) for Talymed, $3,150
      ($1,890-$24,570) for Oasis, and $29,952 ($14,976-$119,808) for Apligraf.
      CONCLUSIONS: The most expensive AWCM for the treatment of VLUs did not appear to
      provide the greatest comparative clinical or cost efficacy. Conclusions must be
      tempered by the small number of available studies (n=3), variability in trial
      duration (from 12 to 24 weeks) and baseline wound characteristics, and
      limitations in study quality. Given the high prevalence, economic burden, and
      substantial disability of VLUs, and the wide variation in costs for AWCMs, payers
      need more high-quality head-to-head comparisons to guide coverage and
      reimbursement determinations for these products.

PMID- 22663171
TI  - Assessment of the relationship between adherence with antiemetic drug therapy and
      control of nausea and vomiting in breast cancer patients receiving anthracycline
      based chemotherapy.
AB  - BACKGROUND: There are little prevalence data in the literature on nonadherence to
      outpatient antiemetic regimens for prophylaxis of chemotherapy-induced nausea and
      vomiting (CINV). It is unclear whether adherence with outpatient antiemetic
      regimens is associated with better CINV control. Our previous survey research
      supports the work of clinical pharmacists in collaborative practice with medical
      oncologists in improving adherence with antiemetic therapy in women undergoing
      highly emetic chemotherapy for breast cancer. OBJECTIVES: To (a) evaluate the
      impact of adherence to delayed antiemetics (days 2-4 following anthracycline
      based chemotherapy) on CINV control in breast cancer patients after anthracycline
      based chemotherapy and (b) identify patient-related factors associated with
      nonadherence to delayed antiemetics. METHODS: A single-center, prospective,
      observational study was conducted from December 2006 to January 2011 in breast
      cancer patients receiving anthracycline-based chemotherapy (doxorubicin or
      epirubicin) and antiemetics at the National Cancer Centre Singapore (NCCS), the
      largest ambulatory cancer center in Singapore. Included patients were aged 21
      years or older with confirmed diagnoses of breast cancer and receiving
      anthracycline-containing chemotherapy with antiemetics. Patients were excluded if
      they (a) were diagnosed with intestinal obstruction or received concurrent
      radiotherapy that predisposed them to nausea and vomiting, (b) had vomited in the
      24 hours preceding chemotherapy, or (c) had brain metastases that would impair
      their judgment. Patients documented in a standardized diary their emesis events,
      severity of nausea, use of rescue therapy with metoclopramide, and compliance
      with dose instructions for antiemetic drug therapy for 5 days: day 1 was the day
      of chemotherapy and first day of antiemetic therapy, and day 5 was the day after
      completion of delayed antiemetic therapy (days 2-4). Three definitions were used
      to describe the CINV outcomes: (a) complete response (no emetic episodes and no
      rescue therapy); (b) complete protection (no emetic episodes, no rescue therapy,
      and no significant nausea [Likert score 2 or less]); and (c) complete control (no
      emetic episodes, no rescue therapy, and no nausea). The delayed (days 2-5 post
      chemotherapy) phase of these endpoints was analyzed. Nonadherence was defined as
      missing at least 1 dose of the delayed antiemetics from the prescribed regimen.
      Pearson chi-square or Fisher's exact tests and multiple logistic regression
      analysis were used to assess the relationship between adherence and CINV
      outcomes. RESULTS: Of 519 eligible patients, 88 (17.0%) patients declined
      participation; 35 (6.7%) were lost to follow-up; and another 35 (6.7%) were
      excluded due to the absence of therapy with delayed antiemetics according to
      guideline protocol. Of the 361 (69.6%) patients included in the final analysis,
      the mean (SD) age was 50.0 (8.9); the majority was Chinese (80.1%) and diagnosed
      with stage 2 or higher breast cancer (88.1%). A total of 152 patients (42.1%)
      self-reported nonadherent use of delayed antiemetics. Among all the nonadherent
      patients (n=152), 16.4% (n=25) achieved complete control; 34.2% (n=52) achieved
      complete protection; and 58.6% (n=89) achieved complete response, compared with
      rates of 26.8% (n=56), 39.7% (n=83), and 62.7% (n=131), respectively, for
      adherent patients (n=209). The rate of adherence to dexamethasone, which was
      prescribed for all study patients, was low (62.6%). After adjusting for potential
      confounders (ethnicity, educational level, and disease stage), adherent patients
      were more likely to achieve complete control of CINV (adjusted odds ratio=1.74,
      95% CI=1.01-3.01, P=0.048). Among the demographic and CINV risk-factor variables,
      higher education, alcohol consumption, and prior exposure to other
      (nonanthracycline-based) chemotherapy regimens were associated with nonadherence
      (P < 0.05). CONCLUSIONS: Although 42% of breast cancer patients receiving
      anthracycline-based chemotherapy were nonadherent with the dose administration
      protocol for post-chemotherapy antiemetic therapy, there was no significant
      difference in control of CINV compared with adherent patients except for the
      category of complete CINV control, defined as no nausea, no emesis, and no use of
      the rescue medication metoclopramide.

PMID- 22663172
TI  - Breaking down barriers to advanced pharmacy practice.

PMID- 22663173
TI  - High-pressure synthesis, crystal structure, and electromagnetic properties of
      CdRh2O4: an analogous oxide of the postspinel mineral MgAl2O4.
AB  - The postspinel mineral MgAl(2)O(4) exists only under the severe pressure
      conditions in the subducted oceanic lithosphere in the Earth's deep interior.
      Here we report that its analogous oxide CdRh(2)O(4) exhibits a structural
      transition to a quenchable postspinel phase under a high pressure of 6 GPa at
      1400  degrees C, which is within the general pressure range of a conventional
      single-stage multianvil system. In addition, the complex magnetic contributions
      to the lattice and metal nonstoichiometry that often complicate investigations of
      other analogues of MgAl(2)O(4) are absent in CdRh(2)O(4). X-ray crystallography
      revealed that this postspinel phase has an orthorhombic CaFe(2)O(4) structure,
      thus making it a practical analogue for investigations into the geophysical role
      of postspinel MgAl(2)O(4). Replacement of Mg(2+) with Cd(2+) appears to be
      effective in lowering the pressure required for transition, as was suggested for
      CdGeO(3). In addition, Rh(3+) could also contribute to this reduction, as many
      analogous Rh oxides of aluminous and silicic minerals have been quenched from
      lower-pressure conditions.

PMID- 22663174
TI  - New nonlinear optical crystal: NaBa4Al2B8O18Cl3.
AB  - Single crystals of NaBa(4)Al(2)B(8)O(18)Cl(3) have been grown with sizes up to 34
      * 34 * 16 mm(3) from the NaF-LiCl flux by the top-seeded solution growth method.
      The compound crystallizes in the tetragonal system, space group P4(2)nm, with a =
      12.0480 (16) A, c = 6.8165 (11) A, alpha = beta = gamma = 90 degrees , and two
      formula units per cell. The NaBa(4)Al(2)B(8)O(18)Cl(3) compound is built up of
      infinite anionic groups of [AlB(4)O(12)](9-) formed by two BO(4) tetrahedra, one
      AlO(4) tetrahedra, and two BO(3) triangles. Optical properties including
      ultraviolet transmission, IR spectrum, and second-harmonic generation of
      NaBa(4)Al(2)B(8)O(18)Cl(3) crystals were reported. Refractive indices were
      measured by the minimum deviation technique and fitted to the Sellmeier
      equations. Thermal properties such as the DSC and thermal expansion were
      reported. The mechanical properties including the hardness, density, and chemical
      stability were also reported.

PMID- 22663176
TI  - Modulation of a photoswitchable dual-color quantum dot containing a photochromic
      FRET acceptor and an internal standard.
AB  - Photoswitchable semiconductor nanoparticles, quantum dots (QDs), couple the
      advantages of conventional QDs with the ability to reversibly modulate the QD
      emission, thereby improving signal detection by rejection of background signals.
      Using a simple coating methodology with polymers incorporating a
      diheteroarylethene photochromic FRET acceptor as well as a spectrally distinct
      organic fluorophore, photoswitchable QDs were prepared that are small,
      biocompatible, and feature ratiometric dual emission. With programmed
      irradiation, the fluorescence intensity ratio can be modified by up to ~100%.

PMID- 22663175
TI  - Development and cross-validation of the in-hospital mortality prediction in
      advanced cancer patients score: a preliminary study.
AB  - PURPOSE: Acute palliative care units (APCUs) provide intensive symptom support
      and transition of care for advanced cancer patients. Better understanding of the
      predictors of in-hospital mortality is needed to facilitate program planning and
      patient care. In this prospective study, we identified predictors of APCU
      mortality, and developed a four-item In-hospital Mortality Prediction in Advanced
      Cancer Patients (IMPACT) predictive model. METHODS: Between April and July 2010,
      we documented baseline demographics, the Edmonton Symptom Assessment Scale
      (ESAS), 80 clinical signs including known prognostic factors, and 26 acute
      complications on admission in consecutive APCU patients. Multivariate logistic
      regression analysis was used to identify factors for inclusion in a nomogram,
      which was cross-validated with bootstrap analysis. RESULTS: Among 151 consecutive
      patients, the median age was 58, 13 (9%) had hematologic malignancies, and 52
      (34%) died in the hospital. In multivariate analysis, factors associated with in
      hospital mortality were advanced education (odds ration [OR]=11.8, p=0.002),
      hematologic malignancies (OR=8.6, p=0.02), delirium (OR=4.3, p=0.02), and high
      ESAS global distress score (OR=20.8, p=0.01). In a nomogram based on these four
      factors, total scores of 6, 10, 14, 17, and 21 corresponded to a risk of death of
      10%, 25%, 50%, 75%, and 90%, respectively. The model has 92% sensitivity and 88%
      specificity for predicting patients at low/high risk of dying in the hospital,
      and a receiver-operator characteristic curve concordance index of 83%.
      CONCLUSIONS: Higher education was associated with increased utilization of the
      interdisciplinary palliative care unit until at the end of life. Patients with
      higher symptom burden, delirium, and hematologic malignancies were also more
      likely to require APCU care until death.

PMID- 22663177
TI  - Experimental evaluation of wellbore integrity along the cement-rock boundary.
AB  - Leakage of CO(2) and brine from geologic storage reservoirs along wellbores is a
      major risk factor to the success of geologic carbon sequestration. We conducted
      multiphase [supercritical (sc)CO(2)-brine] coreflood experiments that simulate a
      leakage pathway along the cement/rock interface. A composite core constructed of
      oil-well cement and siltstone separated by a simulated damage zone (defect)
      containing ground cement and siltstone was flooded with brine + scCO(2) at 10 MPa
      and 60  degrees C parallel to the defect. During coinjection of scCO(2), the
      effective brine permeability decreased from ~200 to 90 mD due to transition to
      two-phase flow and then further declined to 35 mD. CO(2) injection resulted in a
      pH drop from 11 to 4 and carbonate-undersaturated conditions in the produced
      brine. Microscopy revealed leaching and erosion along the defect, a carbonation
      front extending 5 mm into the cement, parallel to the damage zone, and no change
      in the dimensions of the defect. Carbonation of cement does not appear to explain
      the permeability drop, which is attributed to the migration and reprecipitation
      of alteration products derived from cement within the defect. This study shows
      the potential for self-limiting flow along wellbore defects despite flow of
      aggressive scCO(2)-brine mixtures.

PMID- 22663178
TI  - New application of proton nuclear spin relaxation unraveling the intermolecular
      structural features of low-molecular-weight organogel fibers.
AB  - Proton nuclear spin relaxation has been for the first time extensively used for a
      structural and dynamical study of low-molecular-weight organogels. The gelator in
      the present study is a modified phenylalanine amino acid bearing a naphthalimide
      moiety. From T(1) (spin-lattice relaxation time in the laboratory frame) and
      T(1rho) (spin-lattice relaxation time in the rotating frame) measurements, it is
      shown that the visible gelator NMR spectrum below the liquid-gel transition
      temperature corresponds to a so-called isotropic compartment, where gelator
      molecules behave as in a liquid phase but exchange rapidly with the molecules
      constituting the gel structure. This feature allows one to derive, from
      accessible parameters, information about the gel itself. Nuclear Overhauser
      effect spectroscopy (NOESY) experiments have been exploited in view of
      determining not only cross-relaxation rates but also specific longitudinal rates.
      The whole set of relaxation parameters (at 25  degrees C) leads to a correlation
      time of 5 ns for gelator molecules within the gel structure and 150 ps for
      gelator molecules in the isotropic phase. This confirms, on one hand, the
      flexibility of the organogel fibers and, on the other hand, the likely presence
      of clusters in the isotropic phase. Concerning cross-relaxation rates, a thorough
      theoretical investigation in multispin systems of direct and relayed correlations
      in a NOESY spectrum allows one to make conclusions about contacts (around 2-3 A)
      not only between naphtalimide moieties of different gelator molecules but also
      between the phenyl ring and the naphtalimide moiety again of different gelator
      molecules. As a result, not only is the head-to-tail structure of amino acid
      columns confirmed but also the entangling of nearby columns by the naphthalimide
      moieties is demonstrated.

PMID- 22663179
TI  - Validity of the bear tapeworm Diphyllobothrium ursi (Cestoda: Diphyllobothriidae)
      based on morphological and molecular markers.
AB  - The bear tapeworm Diphyllobothrium ursi is described based upon the morphology of
      adult tapeworms recovered from the brown bear (Ursus arctos middendorffi) and
      larval plerocercoids found in sockeye salmon (Oncorhynchus nerka) from Kodiak
      Island in Alaska in 1952. However, in 1987 D. ursi was synonymized with
      Diphyllobothrium dendriticum, and the taxonomic relationship between both species
      has not subsequently been revised. In this study mitochondrial cytochrome c
      oxidase subunit 1 gene (cox1) sequences of holotype and paratype D. ursi
      specimens that had been preserved in a formalin-acetic acid-alcohol solution
      since the time the species was initially described approximately 60 yr ago were
      analyzed. Molecular and phylogenetic analysis of the cox1 sequences revealed that
      D. ursi is more closely related to D. dendriticum than it is to Diphyllobothrium
      nihonkaiense and Diphyllobothrium latum. In addition to molecular evidence,
      differences in the life cycle and ecology of the larval plerocercoids between D.
      ursi and D. dendriticum also suggest that D. ursi is a distinct species, separate
      from D. dendriticum and D. nihonkaiense, and also possibly from D. latum .

PMID- 22663180
TI  - Synchronous emission from nanometric silver particles through plasmonic coupling
      on silver nanowires.
AB  - We investigated silver nanowires using correlative wide-field fluorescence and
      transmission electron microscopy. In the wide-field fluorescence images,
      synchronous emission from different distinct positions along the silver nanowires
      was observed. The sites of emission were separated spatially by up to several
      micrometers. Nanowires emitting in such cooperative manner were then also
      investigated with a combination of transmission electron microscopy based
      techniques, such as high-resolution, bright-field imaging, electron diffraction,
      high-angle annular dark-field imaging, and energy-dispersive X-ray spectroscopy.
      In particular, analyzing the chemical composition of the emissive areas using
      energy-dispersive X-ray spectroscopy led to the model that the active emissive
      centers are small silver clusters generated photochemically and that individual
      clusters are coupled via surface plasmons of the nanowire.

PMID- 22663181
TI  - Effects of esterified lactoferrin and lactoferrin on control of postharvest blue
      mold of apple fruit and their possible mechanisms of action.
AB  - The effects of esterified lactoferrin (ELF) and lactoferrin (LF) on blue mold
      caused by  Penicillium expansum  in apple fruit stored at 25  degrees C were
      investigated. Both ELF and LF provided an effective control and strongly
      inhibited spore germination and germ tube elongation of P. expansum in vitro.
      Assessment by propidium iodide staining combined with fluorescent microscopy
      revealed that the plasma membrane of P. expansum spores was damaged more
      seriously by ELF than by LF treatment, and the leakage of protein and sugar was
      higher from ELF-treated mycelia. Interestingly, ELF treatment induced a
      significant increase in the activities of chitinase, beta-1,3-glucanase, and
      peroxidase in apple fruit, whereas both LF treatment and the control showed no
      obvious difference. These findings indicated that the effects of ELF on blue mold
      in apple fruit might be associated with the direct fungitoxic property against
      the pathogens and the elicitation of defense-related enzymes in fruit.

PMID- 22663182
TI  - Charge heterogeneity of monoclonal antibodies by multiplexed imaged capillary
      isoelectric focusing immunoassay with chemiluminescence detection.
AB  - Characterization of charge heterogeneity of recombinant monoclonal antibodies
      (mAbs) requires high throughput analytical methods to support clone selection and
      formulation screens. We applied the NanoPro technology to rapidly measure
      relative charge distribution of mAbs in early stage process development. The
      NanoPro is a multiplexed capillary-based isoelectric immunoassay with whole
      column imaging detection. This assay offers specificity, speed and sensitivity
      advantages over conventional capillary isoelectric focusing (CIEF) platforms.
      After CIEF, charge variants are photochemically immobilized to the wall of a
      short coated capillary. Once immobilized, mAbs are probed using a secondary anti
      IgG conjugated with horseradish peroxidase. After flushing away excess reagents,
      secondary antibodies bound to their targets are then detected by
      chemiluminescence upon incubation with peroxidase reactive substrates. Charge
      heterogeneity as determined by chemiluminescence was similar to that measured by
      conventional CIEF technology with absorbance detection for purified mAbs and
      contaminated mAbs derived directly from host cellular extract. Upon method
      optimization, the automated CIEF immunoassay was applied to several mAbs of
      varying isoelectric points, demonstrating the suitability of NanoPro as a rugged
      high-throughput product characterization tool. Furthermore, qualification of
      detection sensitivity, precision, and dynamic range are reported with discussion
      of its advantages as an alternative approach to rapidly characterize charge
      variants during process development of mAbs.

PMID- 22663183
TI  - Pulmonary delivery of interleukin-7 provides efficient and safe delivery to the
      aging immune system.
AB  - Age-associated atrophy of the thymus with coincident reduction in thymopoeisis,
      decline in thymic output, and subsequent immune dysfunction has been reversed by
      the use of interleukin-7 (IL-7). In the earlier studies and in clinical trials,
      delivery of IL-7 has been by multiple injections over several days to maintain
      effective activity levels in the tissues. This is unlikely to meet with high
      compliance rates in future clinical use, and so we tested alternate routes of
      delivery using a technique involving tagging IL-7 with fluorescent dye that emits
      in the near-infrared region and whose fluorescence can be visualized within the
      tissues of live animals. We have shown that intratracheal instillation, enabling
      transfer through the lungs, provides an effective route for delivering IL-7 into
      the bloodstream and from there into the tissues in older animals. Delivery is
      rapid and widespread tissue distribution is seen. Comparison of administration
      either subcutaneously or by instillation reveals that IL-7 delivery by the
      pulmonary route provides significantly greater transmission to lymphoid tissues
      when compared with injection. In functional assessment studies, pulmonary
      administration led to significantly improved intrathymic T cell development in
      older animals when compared with IL-7 delivered by injection. Furthermore, in
      these older animals, delivery of IL-7 by intratracheal instillation was not
      accompanied by any apparent adverse events when compared with controls receiving
      saline vehicle by instillation or animals receiving IL-7 by subcutaneous
      injection.

PMID- 22663184
TI  - Composite films of arabinoxylan and fibrous sepiolite: morphological, mechanical,
      and barrier properties.
AB  - Hemicelluloses represent a largely unutilized resource for future bioderived
      films in packaging and other applications. However, improvement of film
      properties is needed in order to transfer this potential into reality. In this
      context, sepiolite, a fibrous clay, was investigated as an additive to enhance
      the properties of rye flour arabinoxylan. Composite films cast from arabinoxylan
      solutions and sepiolite suspensions in water were transparent or semitransparent
      at additive loadings in the 2.5-10 wt % range. Scanning electron microscopy
      showed that the sepiolite was well dispersed in the arabinoxylan films and
      sepiolite fiber aggregation was not found. FT-IR spectroscopy provided some
      evidence for hydrogen bonding between sepiolite and arabinoxylan. Consistent with
      these findings, mechanical testing showed increases in film stiffness and
      strength with sepiolite addition and the effect of poly(ethylene glycol) methyl
      ether (mPEG) plasticizer addition. Incorporation of sepiolite did not
      significantly influence the thermal degradation or the gas barrier properties of
      arabinoxylan films, which is likely a consequence of sepiolite fiber morphology.
      In summary, sepiolite was shown to have potential as an additive to obtain
      stronger hemicellulose films although other approaches, possibly in combination
      with the use of sepiolite, would be needed if enhanced film barrier properties
      are required for specific applications. 

PMID- 22663186
TI  - Antimicrobial susceptibility, pulsed-field gel electrophoresis, and multi-locus
      sequence typing of Campylobacter coli in swine before, during, and after the
      slaughter process.
AB  - The objective of this study was to determine persistence of clonal strains from
      farm to retail by assessing the clonal relatedness of Campylobacter coli isolated
      on farm, peri-harvest, and at processing from 11 individually identified pigs.
      Phenotypic (antimicrobial susceptibility) and genotypic (pulsed field gel
      electrophoresis [PFGE] and multi-locus sequence typing [MLST]) characterization
      of isolates was conducted. There was high genetic diversity of Campylobacter
      isolates from on-farm fecal samples. Campylobacter isolates from farm, post
      evisceration, hide, and carcass samples showed similar phenotypes and belonged to
      the same genotypic clusters based on PFGE and sequence types (STs) based on MLST.
      Five STs that have not been previously reported were identified (ST-4083, ST
      4084, ST-4085, ST-4086, ST-4087). Despite high genotypic diversity of C. coli on
      farm, retail meat products were consistently contaminated with isolates of the
      same STs, particularly ST854 and ST1056, as isolates collected from previous
      stages confirming persistence of strains from pre- to post-harvest.

PMID- 22663187
TI  - Prevalence and serotypes of Listeria monocytogenes contamination in Chinese beef
      processing plants.
AB  - The aim of this work was to study the epidemiology of Listeria spp., particularly
      Listeria monocytogenes, and to identify the serotypes present in contaminated
      samples from beef processing plants in China. A total of 439 samples were
      obtained from bovine feces, hides, and carcasses at three commercial processing
      plants. A standard protocol (ISO 11290-1) was followed to detect Listeria spp.
      and L. monocytogenes, and multiplex polymerase chain reaction was used to
      identify the various L. monocytogenes serotypes. The overall prevalences of
      Listeria spp. and L. monocytogenes were 65.6% and 26.4%, respectively, and the
      contamination was highest in the hide samples. The identified L. monocytogenes
      serotypes were 1/2c and 1/2a. The results of the current study indicate that
      Listeria spp. contamination is common in Chinese beef processing plants; specific
      measures should be taken to prevent and/or treat L. monocytogenes contamination
      of feces and hides in beef slaughter plants. Furthermore, because Listeria spp.
      contamination was found to be prevalent, it should, therefore, be studied
      further. The prevention of cases of sporadic listeriosis in China should also be
      addressed.

PMID- 22663188
TI  - Antibacterial effects of plant-derived extracts on methicillin-resistant
      Staphylococcus aureus.
AB  - Natural chemicals have been reported to have antibacterial effects against a
      variety of bacteria. The present study evaluated the antibacterial effects of
      commercially available grape-seed extract (GSE), pomegranate polyphenols (PP),
      and lab-prepared cranberry proanthocyanidins (C-PAC) against two strains of
      methicillin-resistant Staphylococcus aureus (MRSA). GSE, PP, and C-PAC at
      concentrations of 2 mg/mL, 10 mg/mL, or controls were mixed with equal volumes of
      overnight cultures of MRSA at ~6 log10 colony-forming units (CFU)/mL and
      incubated for 0, 1, 2, 8, and 24 h at 37 degrees C. Treatments were
      neutralized/stopped using tryptic soy broth containing 3% beef extract. Serial
      dilutions of the treated MRSA strains and controls were spread-plated on
      trypticase soy agar and incubated for 24-48 h at 37 degrees C and colonies were
      counted. Among the three tested agents, GSE at 1 and 5 mg/mL was found to be most
      effective against MRSA, resulting in a 2.9-4.0 log10 CFU/mL reduction of both
      strains after 2 h at 37 degrees C. PP at 1 and 5 mg/mL was found to cause 1.1-2.3
      log10 CFU/mL reduction, while C-PAC at 1 mg/mL caused <1 log10 CFU/mL reduction
      of the two MRSA strains after 2 h at 37 degrees C. All three extracts at the
      tested concentrations decreased the two MRSA strains to undetectable levels
      within 24 h, with the exception of 1 mg/mL PP for strain 33591. Scanning electron
      microscopy of MRSA after 2 h of treatment showed that GSE and PP caused bacterial
      cell wall alteration, with negligible effect observed by C-PAC treatment.
      However, the in vivo activity and clinical safety applications of GSE, PP, and C
      PAC need to be evaluated before suggestion for use as a treatment/control
      measure.

PMID- 22663185
TI  - Antiretroviral adherence during pregnancy and postpartum in Latin America.
AB  - Adherence to antiretrovirals by pregnant women (and postpartum women if
      breastfeeding) is crucial to effectively decrease maternal viral load and
      decrease the risk of mother-to-child transmission of HIV. Our objectives were to
      describe self-reported adherence to antiretrovirals during the antepartum (after
      22 weeks of pregnancy) and postpartum periods (6-12 weeks and 6 months), and
      identify predictors of adherence among HIV-infected women enrolled and followed
      in a prospective cohort study from June 2008 to June 2010 at multiple sites in
      Latin America. Adherence was evaluated using the number of missed and expected
      doses during the 3 days before the study visit. At the pre-delivery visit, 340 of
      376 women (90%) reported perfect adherence. This rate significantly decreased by
      6-12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p<0.01). The
      odds for less than perfect adherence at the pre-delivery visit was significantly
      higher for pregnant women with current tobacco use (odds ratio [OR]=2.9, 95%
      confidence interval [CI]: 1.46-6.14; p=0.0029). At 6-12 weeks postpartum, the
      probability of non-perfect adherence increased by 6% for each 1 year increase in
      age (OR=1.06, 95% CI: 1.00-1.12, p=0.0497). At 6 months postpartum, the odds of
      nonperfect adherence was higher for those who were currently using alcohol
      (OR=3.04, 95% CI: 1.34-6.90; p=0.0079). Although a self-report measure of
      adherence based on only 3 days may lead to overestimation of actual adherence
      over time, women with perfect adherence had lower viral loads and higher CD4
      counts. Adherence to antiretrovirals decreased significantly postpartum.
      Interventions should target women at high risk for lower adherence during
      pregnancy and postpartum, including tobacco and alcohol users.

PMID- 22663189
TI  - Clinical translation of folate receptor-targeted therapeutics.
AB  - INTRODUCTION: Folate receptor-alpha (FR-alpha) has been established as a membrane
      marker for ovarian cancer. In addition, it is frequently overexpressed in other
      major types of epithelial tumors. FR-alpha-based tumor-targeted therapy and drug
      carriers have been an active area of laboratory research for more than 20 years.
      Recently, there has been a great increase in the effort to finally translate this
      promising technology into the clinic and bring FR-targeted therapeutics into the
      market. AREAS COVERED: Two FR-targeted therapeutic agents have moved into Phase
      III clinical trials, the monoclonal antibody farletuzumab and the low molecular
      weight vintafolide, combined with etarfolatide as a companion imaging agent,
      representing two alternative strategies for targeting the FR. EXPERT OPINION:
      Each of the two strategies has advantages and disadvantages. Identification of
      the best target patient population is likely critical to the ultimate success of
      FR-targeted agents in the clinic. A successful clinical strategy may require the
      integration between FR expression analysis and an optimal combination of FR
      targeted therapy and standard chemotherapy. Advancement into Phase III trials and
      the ongoing clinical development of several additional folate conjugates are
      likely to usher in a new era of clinical translation and validation of FR
      targeted imaging and therapeutic agents.

PMID- 22663190
TI  - Polyhydroxylated steroidal glycosides from Paris polyphylla.
AB  - Three new steroidal saponins, parisyunnanosides G-I (1-3), one new C(21)
      steroidal glycoside, parisyunnanoside J (4), and three known compounds,
      padelaoside B (5), pinnatasterone (6), and 20-hydroxyecdyson (7), were isolated
      from the rhizomes of Paris polyphylla Smith var. yunnanensis. Compounds 1 and 3
      have unique trisdesmoside structures that include a C-21 beta-d-galactopyranose
      moiety. All compounds were evaluated for their cytotoxicity against human CCRF
      leukemia cells.

PMID- 22663192
TI  - Hydrido copper clusters supported by dithiocarbamates: oxidative hydride removal
      and neutron diffraction analysis of [Cu7(H){S2C(aza-15-crown-5)}6].
AB  - Reactions of Cu(I) salts with Na(S(2)CR) (R = N(n)Pr(2), NEt(2), aza-15-crown-5),
      and (Bu(4)N)(BH(4)) in an 8:6:1 ratio in CH(3)CN solution at room temperature
      yield the monocationic hydride-centered octanuclear Cu(I) clusters,
      [Cu(8)(H){S(2)CR}(6)](PF(6)) (R = N(n)Pr(2), 1(H); NEt(2), 2(H); aza-15-crown-5,
      3(H)). Further reactions of [Cu(8)(H){S(2)CR}(6)](PF(6)) with 1 equiv of
      (Bu(4)N)(BH(4)) produced neutral heptanuclear copper clusters,
      [Cu(7)(H){S(2)CR}(6)] (R = N(n)Pr(2), 4(H); NEt(2), 5(H); aza-15-crown-5, 6(H))
      and clusters 4-6 can also be generated from the reaction of Cu(BF(4))(2),
      Na(S(2)CR), and (Bu(4)N)(BH(4)) in a 7:6:8 molar ratio in CH(3)CN. Reformation of
      cationic Cu(I)(8) clusters by adding 1 equiv of Cu(I) salt to the neutral Cu(7)
      clusters in solution is observed. Intriguingly, the central hydride in
      [Cu(8)(H){S(2)CN(n)Pr(2)}(6)](PF(6)) can be oxidatively removed as H(2) by
      Ce(NO(3))(6)(2-) to yield [Cu(II)(S(2)CN(n)Pr(2))(2)] exploiting the redox
      tolerant nature of dithiocarbamates. Regeneration of hydride-centered octanuclear
      copper clusters from the [Cu(II)(S(2)CN(n)Pr(2))(2)] can be achieved by reaction
      with Cu(I) ions and borohydride. The hydride release and regeneration of Cu(I)(8)
      was monitored by UV-visible titration experiments. To our knowledge, this is the
      first time that hydride encapsulated within a copper cluster can be released as
      H(2) via chemical means. All complexes have been fully characterized by (1)H NMR,
      FT-IR, UV-vis, and elemental analysis, and molecular structures of 1(H), 2(H),
      and 6(H) were clearly established by single-crystal X-ray diffraction. Both 1(H)
      and 2(H) exhibit a tetracapped tetrahedral Cu(8) skeleton, which is inscribed
      within a S(12) icosahedron constituted by six dialkyl dithiocarbamate ligands in
      a tetrametallic-tetraconnective (MU(2), MU(2)) bonding mode. The copper framework
      of 6(H) is a tricapped distorted tetrahedron in which the four-coordinate hydride
      is demonstrated to occupy the central site by single crystal neutron diffraction.
      Compounds 1-3 exhibit a yellow emission in both the solid state and in solution
      under UV irradiation at 77 K, and the structureless emission is assigned as a
      (3)metal to ligand charge transfer (MLCT) excited state. Density functional
      theory (DFT) and time-dependent density functional theory (TDDFT) calculations on
      model compounds match the experimental structures and provide rationalization of
      their bonding and optical properties.

PMID- 22663195
TI  - A redescription of Myxobolus inornatus from young-of-the-year smallmouth bass
      (Micropterus dolomieu).
AB  - During investigations of young-of-the year smallmouth bass ( Micropterus dolomieu
      ) mortalities in the Susquehanna River, Pennsylvania, U.S.A. and affected
      tributaries, raised areas were noted in the muscle in the vicinity of the caudal
      peduncle. The raised areas were caused by plasmodia of a myxozoan parasite.
      Spores found within plasmodia were similar to those of Myxobolus inornatus
      previously described from the caudal peduncle of fingerling largemouth bass (
      Micropterus salmoides ) in Montana. Here, M. inornatus is redescribed based on
      histologic comparisons and spore measurements. The addition of spore photographs,
      line drawings, a voucher specimen, and partial small-subunit ribosomal (rSSU) DNA
      gene sequence are new in this study. This is also the first description of M.
      inornatus from smallmouth bass. The plasmodia of M. inornatus were grossly
      observed at the base of the caudal and dorsal fins and were 280.3 +/- 33.5 (range
      77.1-920.3) MUm long and 320.6 +/- 41.0 (range 74.85-898.4) MUm wide. In some
      instances, plasmodia of M. inornatus were large enough to rupture the epidermis
      or were associated with misaligned vertebrae. The slightly pyriform spores were
      11.3 +/- 0.2 (range 8.6-17.4) MUm in length and 8.6 +/- 0.2 (range 7.1-13.7) MUm
      wide with an iodinophilous vacuole and a sutural ridge with 8 to 10 sutural
      folds. The SSU rDNA gene sequence places M. inornatus in a sister group with
      Myxobolus osburni .

PMID- 22663194
TI  - Injectable polyplex hydrogel for localized and long-term delivery of siRNA.
AB  - Here, we describe a concept for localized and long-term delivery of short
      interfering RNA (siRNA) using an injectable polyplex hydrogel possessing
      thermosensitivity and biodegradability properties. We prepared a low molecular
      weight polyethyleneimine-poly(organophosphazene) conjugate as a thermosensitive
      and cationic polymer that has a cleavable ester linkage. The conjugates formed
      about 100 nm sized polyplexes with siRNAs, and the polyplex solution turned into
      a polyplex hydrogel at body temperature via a hydrophobic interaction. We
      injected the polyplex hydrogel with siRNA of cyclin B1, an essential protein for
      controlling the cell cycle, into the tumor xenograft model. Polyplexes were
      slowly released from the polyplex hydrogel by dissolution and degradation,
      allowing an in vivo antitumor effect via cyclin B1 gene silencing for 4 weeks
      with only a single injection.

PMID- 22663191
TI  - Sex hormones and the QT interval: a review.
AB  - A prolonged QT interval is a marker for an increased risk of ventricular
      tachyarrhythmias. Both endogenous and exogenous sex hormones have been shown to
      affect the QT interval. Endogenous testosterone and progesterone shorten the
      action potential, and estrogen lengthens the QT interval. During a single
      menstrual cycle, progesterone levels, but not estrogen levels, have the dominant
      effect on ventricular repolarization in women. Studies of menopausal hormone
      therapy (MHT) in the form of estrogen-alone therapy (ET) and estrogen plus
      progesterone therapy (EPT) have suggested a counterbalancing effect of exogenous
      estrogen and progesterone on the QT. Specifically, ET lengthens the QT, whereas
      EPT has no effect. To date, there are no studies on oral contraception (OC) and
      the QT interval, and future research is needed. This review outlines the current
      literature on sex hormones and QT interval, including the endogenous effects of
      estrogen, progesterone, and testosterone and the exogenous effects of estrogen
      and progesterone therapy in the forms of MHT and hormone contraception. Further,
      we review the potential mechanisms and pathophysiology of sex hormones on the QT
      interval.

PMID- 22663198
TI  - Gold inlay procedures for extensive cervical lesions.

PMID- 22663197
TI  - Effects of food-simulating liquids on surface properties of giomer restoratives.
AB  - This study examined the effects of food-simulating liquid (FSL) on the hardness
      and roughness of giomer restoratives based on pre-reacted glass ionomer (PRG)
      technology. The materials investigated included a regular (Beautifil II [BT]) and
      a recently introduced injectable (Beautifil Flow Plus F00 [BF]) hybrid PRG
      composite. A direct hybrid composite (Filtek Z250 [ZT]) and an indirect hybrid
      composite (Ceramage [CM]) were used for comparison. The materials were placed
      into customized square molds (5 mm * 5 mm * 2.5 mm), covered with Mylar strips,
      and cured according to manufacturers' instructions. The materials were then
      conditioned in air (control), distilled water, 50% ethanol solution, and 0.02 N
      citric acid at 37 degrees C for seven days. Specimens (n=6) were then subjected
      to hardness testing (Knoop) and surface profilometry. Data were analyzed using
      one-way analysis of variance and post hoc Scheffe test (p<0.05). Mean Knoop
      hardness values for the control group (air) ranged from 53.4 +/- 3.4 (BF) to 89.5
      +/- 5.2 (ZT), while mean surface roughness values values ranged from 0.014 +/-
      0.002 (ZT) to 0.032 +/- 0.001 (BT). All materials were significantly softened by
      FSL. The degree of softening by the different FSLs was material dependent. The
      hardness of giomers was most affected by citric acid and ethanol. The smoothest
      surface was generally observed with the control group. Giomer restoratives were
      significantly roughened by citric acid.

PMID- 22663196
TI  - Phosphoric acid-etching promotes bond strength and formation of acid-base
      resistant zone on enamel.
AB  - This study examined the effect of phosphoric acid (PA) etching on the bond
      strength and acid-base resistant zone (ABRZ) formation of a two-step self-etching
      adhesive (SEA) system to enamel. An etch-and-rinse adhesive (EAR) system Single
      Bond (SB) and a two-step SEA system Clearfil SE Bond (SE) were used. Human teeth
      were randomly divided into four groups according to different adhesive
      treatments: 1) SB; 2) SE; 3) 35% PA etching->SE primer->SE adhesive (PA/SEp+a);
      (4) 35% PA etching->SE adhesive (PA/SEa). Microshear bond strength to enamel was
      measured and then statistically analyzed using one-way analysis of variance and
      the Tukey honestly significant difference test. The failure mode was recorded and
      analyzed by chi( 2 ) test. The etching pattern of the enamel surface was observed
      with scanning electron microscope (SEM). The bonded interface was exposed to a
      demineralizing solution (pH=4.5) for 4.5 hours and then 5% sodium hypochlorite
      with ultrasonication for 30 minutes. After argon-ion etching, the interfacial
      ultrastructure was observed using SEM. The microshear bond strength to enamel of
      the SE group was significantly lower (p<0.05) than that of the three PA-etched
      groups, although the latter three were not significantly different from one
      another. The ABRZ was detected in all the groups. In morphological observation,
      the ABRZ in the three PA-etched groups were obviously thicker compared with the
      SE group with an irregular wave-shaped edge.

PMID- 22663199
TI  - Tungsten-catalyzed heterocycloisomerization approach to 4,5-dihydro
      benzo[b]furans and -indoles.
AB  - A W(CO)(5).THF-catalyzed cycloisomerization of bicyclo[4.1.0] substrates to
      afford mono C4-substituted 4,5-dihydro-benzo[b]furans and -indoles is reported.
      The title compounds are versatile intermediates that lead to a range of fused
      bicycles including the cores of various furan-, benzofuran-, and indole
      containing natural products. In many cases, the functionalization of the dihydro
      benzo[b]furans and -indoles is orthogonal to that of the corresponding
      benzofurans and indoles and, thus, offers complementary approaches for synthesis.

PMID- 22663200
TI  - Cation disordering by rapid crystal growth in olivine-phosphate nanocrystals.
AB  - On the basis of Pauling's first rule for ionic bonding, the coordination number
      of cations with oxygen anions can be determined by comparison of their relative
      ionic size ratio. In contrast to simple oxides, various site occupancies by
      multicomponent cations with similar sizes usually occur in complex oxides,
      resulting in distinct physical properties. Through an unprecedented combination
      of in situ high-temperature high-resolution electron microscopy, crystallographic
      image processing, geometric phase analysis, and neutron powder diffraction, we
      directly demonstrate that while the initial crystallites after nucleation during
      crystallization have a very high degree of ordering, significant local cation
      disordering is induced by rapid crystal growth in Li-intercalation metal
      phosphate nanocrystals. The findings in this study show that control of
      subsequent crystal growth during coarsening is of great importance to attain a
      high degree of cation ordering, emphasizing the significance of atomic-level
      visualization in real time.

PMID- 22663201
TI  - Industry.

PMID- 22663202
TI  - Advisory board.

PMID- 22663203
TI  - Thermo Electron CORPORATION.

PMID- 22663204
TI  - AeroVironment Inc.

PMID- 22663206
TI  - Pacific scientific.

PMID- 22663205
TI  - The chlorination question.

PMID- 22663207
TI  - Columbia scientific industries corporation.

PMID- 22663208
TI  - Humic substances.

PMID- 22663209
TI  - Trying to track down chemistry professor?

PMID- 22663210
TI  - Chemistry in medicine.

PMID- 22663211
TI  - Acid rain: legal and political fallout.

PMID- 22663214
TI  - Foremost-McKesson Research Center.

PMID- 22663212
TI  - Disposal of high-level radioactive wastes by burial in the sea floor.

PMID- 22663215
TI  - Mobile mass spectrometry.

PMID- 22663216
TI  - The Project SEED summer program.

PMID- 22663219
TI  - Products.

PMID- 22663218
TI  - Pesticide effects on aquatic habitats.

PMID- 22663220
TI  - Atmospheric aerosol.

PMID- 22663222
TI  - Fill a staff position on capitol hill.

PMID- 22663221
TI  - An appeal for quality.

PMID- 22663223
TI  - NOt just a book... A Celebration!

PMID- 22663224
TI  - Literature.

PMID- 22663227
TI  - Foxboro company.

PMID- 22663225
TI  - The directory of graduate research 1981.

PMID- 22663228
TI  - Acid precipitation.

PMID- 22663229
TI  - Correction.

PMID- 22663230
TI  - Research appliance company.

PMID- 22663231
TI  - Dietary cadmium.

PMID- 22663232
TI  - Acs analytical books.

PMID- 22663233
TI  - Courses.

PMID- 22663234
TI  - New environmental books from acs.

PMID- 22663235
TI  - professional consulting services directory.

PMID- 22663237
TI  - International.

PMID- 22663238
TI  - Classified section.

PMID- 22663240
TI  - ACS Reprint Collections for Environmental Scientists & Engineers.

PMID- 22663242
TI  - Current Research Author's Guide.

PMID- 22663241
TI  - Editorial policy.

PMID- 22663243
TI  - Environmental testing and certification corporation.

PMID- 22663244
TI  - ACS Sales Office.

PMID- 22663245
TI  - Matheson.

PMID- 22663246
TI  - International.

PMID- 22663247
TI  - Washington.

PMID- 22663248
TI  - Preparation and biological evaluation of (64)Cu labeled Tyr(3)-octreotate using a
      phosphonic acid-based cross-bridged macrocyclic chelator.
AB  - Somatostatin receptors (SSTr) are overexpressed in a wide range of neuroendocrine
      tumors, making them excellent targets for nuclear imaging and therapy, and
      radiolabeled somatostatin analogues have been investigated for positron emission
      tomography imaging and radionuclide therapy of SSTr-positive tumors, especially
      of the subtype-2 (SSTr2). The aim of this study was to develop a somatostatin
      analogue, Tyr(3)-octreotate (Y3-TATE), conjugated to a novel cross-bridged
      macrocyclic chelator, 11-carboxymethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane
      4-methanephosphonic acid (CB-TE1A1P). Unlike traditional cross-bridged
      macrocycles, such as 4,11-bis(carboxymethyl)-1,4,8,11
      tetraazabicyclo[6.6.2]hexadecane (CB-TE2A), CB-TE1A1P-Y3-TATE was radiolabeled
      with (64)Cu in high purity and high specific activity using mild conditions.
      Saturation binding assays revealed that (64)Cu-CB-TE1A1P-Y3-TATE had comparable
      binding affinity but bound to more binding sites in AR42J rat pancreatic tumor
      cell membranes than (64)Cu-CB-TE2A-Y3-TATE. Both radiopharmaceuticals showed
      comparable uptake in SSTr2 positive tissues in AR42J tumor-bearing rats. (64)Cu
      CB-TE1A1P-Y3-TATE demonstrated improved blood clearance compared to (64)Cu-CB
      TE2A-Y3-TATE, as the tumor/blood ratios of (64)Cu-CB-TE1A1P-Y3-TATE were shown to
      be significantly higher than those of (64)Cu-CB-TE2A-Y3-TATE at 4 and 24 h
      postinjection. (64)Cu-CB-TE1A1P-Y3-TATE, in spite of a relatively high kidney
      uptake, accumulated less in nontarget organs such as liver, lung, and bone. Small
      animal PET/CT imaging of (64)Cu-CB-TE1A1P-Y3-TATE in AR42J tumor bearing rats
      validated significant uptake and good contrast in the tumor. This study suggests
      that CB-TE1A1P is a promising bifunctional chelator for (64)Cu-labeled for Y3
      TATE, owing to high binding affinity and target tissue uptake, the ability to
      radiolabel the agent at lower temperatures, and improved tumor/nontarget organ
      ratios over (64)Cu-CB-TE2A-Y3-TATE.

PMID- 22663249
TI  - Microemulsions for oral administration and their therapeutic applications.
AB  - INTRODUCTION: The microemulsion concept was introduced in 1943 by Hoar and
      Schulman. Self-microemulsifying drug delivery systems (S(M)EDDS) are much more
      recent and can be described as isotropic solutions of oils and surfactants that
      form oil-in-water O/W microemulsions when they are poured into an aqueous medium.
      When they are presented as soft capsules for oral delivery, S(M)EDDS have the
      ability to considerably improve the intestinal absorption of agents that are
      incorporated into the S(M)EDDS. Forty percent of newly discovered drug candidates
      have little or no water solubility and therefore have low and/or variable
      bioavailability profiles. Many of these drugs are good candidates for formulation
      into S(M)EDDS. AREAS COVERED: This paper describes the preparation and assessment
      of these formulations and their current applications. The characterisation of
      this type of formulation has improved, and in vitro models (Caco-2 cell cultures,
      Ussing chambers, the everted sac technique, etc.) can be used for screening
      different formulations. It describes also marketed formulations (i.e.,
      cyclosporin and saquinavir S(M)EDDS) and some other formulations. EXPERT OPINION:
      Actual applications of S(M)EDDS remain rare. The first drug marketed as a
      S(M)EDDS was cyclosporin, and it had significantly improved bioavailability
      compared with the conventional solution. In the last decade, several S(M)EDDS
      loaded with antiviral drugs (e.g., ritonavir, saquinavir) were tested for
      treatment of HIV infection, but the relative improvement in clinical benefit was
      not significant. The S(M)EDDS formulation of Norvir(r) (soft capsules) has been
      withdrawn in some countries.

PMID- 22663251
TI  - Quality of life six months after lung cancer surgery is associated with long-term
      survival.
AB  - BACKGROUND: The aim of this study was to analyze the association between quality
      of life six months following lung cancer surgery and survival. METHODS: In a
      prospective population-based cohort study, quality of life was estimated by the
      Medical Outcomes Study 36-Item Short Form (SF-36) questionnaire before and six
      months after surgery for lung cancer. Cox regression models adjusting for
      potential confounding factors were used to analyze the association between SF-36
      scores six months after surgery and survival. We also estimated the risk of death
      in patients scoring below the normal population mean at six months after surgery.
      RESULTS: We included 249 patients, and 79 patients were excluded because of
      histopathology other than primary lung cancer. After six months, 11 patients had
      died, and 18 patients did not respond to the second SF-36 questionnaire, leaving
      a study population of 141 patients with SF-36 data from both baseline and follow
      up. During a median follow-up of 4.0 years, 35 deaths occurred. The SF-36
      physical and mental component summary scores assessed at six months after lung
      cancer surgery were significantly associated with survival. Mental component
      summary scores below the mean of the age- and gender-matched normal population
      were associated with a three-fold increase in the risk of death. CONCLUSIONS:
      Quality of life scores six months after surgery contained prognostic information
      regarding long-term survival that was independent of baseline scores. If these
      findings can be validated, cross-sectional post-treatment measurements of quality
      of life can prove valuable, especially when baseline information is unavailable.

PMID- 22663252
TI  - Alternate monolayers of CdSe nanocrystals and perylene tetracarboxylate: quantum
      dot hypersensitization for dye-sensitized solar cells.
AB  - Mono- and multilayers from CdSe nanocrystal dispersion and perylene
      tetracarboxylate solution are reported for the first time. The layers were
      investigated by UV-visible spectroscopy, cyclic voltammetry, photoconductivity,
      and photoelectrochemical techniques. The n-type organic semiconductor gives
      enhanced photoconductivity to the CdSe-NC multilayer structure. The photoactive
      perylene monolayer acts also as hypersensitizer of CdSe-NC structures. The
      perylene-modified CdSe-NC monolayer on indium tin oxide (ITO) electrode in a
      three-electrode photoelectrochemical cell upon illumination in the presence of
      oxygen generates an intense steady photocurrent as high as 10-20 times that
      expected from the individual contributions of perylene and CdSe-NCs. The
      hypersensitization mechanism is discussed on the basis of the energy level
      diagram of the components. 

PMID- 22663254
TI  - Periodic mesoporous organosilica as a multifunctional nanodevice for large-scale
      characterization of membrane proteins.
AB  - A versatile protocol has been developed for large-scale characterization of
      hydrophobic membrane proteins based on the periodic mesoporous organosilica (PMO)
      acting as both an extractor for hydrophobic substrate capture and a nanoreactor
      for efficient in situ digestion. With introduction of organic groups in the pore
      frameworks and the presence of hydrophilic silanol groups on the surface, PMO can
      be well-dispersed into not only an organic solution to concentrate the dissolved
      membrane proteins but also an aqueous solution containing enzymes for sequential
      rapid proteolysis in the nanopores. The unique amphiphilic property of PMO
      ensures a facile switch in different solutions to realize the processes of
      substrate dissolution, enrichment, and digestion effectively. Furthermore, this
      novel PMO-assisted protocol has been successfully applied for identification of
      complex membrane proteins extracted from mouse liver as proof of general
      applicability.

PMID- 22663253
TI  - PET evidence for a role for striatal dopamine in the attentional blink:
      functional implications.
AB  - Our outside world changes continuously, for example, when driving through
      traffic. An important question is how our brain deals with this constant barrage
      of rapidly changing sensory input and flexibly selects only newly goal-relevant
      information for further capacity-limited processing in working memory. The
      challenge our brain faces is experimentally captured by the attentional blink
      (AB): an impairment in detecting the second of two target stimuli presented in
      close temporal proximity among distracters. Many theories have been proposed to
      explain this deficit in processing goal-relevant information, with some
      attributing the AB to capacity limitations related to encoding of the first
      target and others assigning a critical role to on-line selection mechanisms that
      control access to working memory. The current study examined the role of striatal
      dopamine in the AB, given its known role in regulating the contents of working
      memory. Specifically, participants performed an AB task and their basal level of
      dopamine D2-like receptor binding was measured using PET and [F-18]fallypride. As
      predicted, individual differences analyses showed that greater D2-like receptor
      binding in the striatum was associated with a larger AB, implicating striatal
      dopamine and mechanisms that control access to working memory in the AB.
      Specifically, we propose that striatal dopamine may determine the AB by
      regulating the threshold for working memory updating, providing a testable
      physiological basis for this deficit in gating rapidly changing visual
      information. A challenge for current models of the AB lies in connecting more
      directly to these neurobiological data.

PMID- 22663250
TI  - Use of specific antiretroviral regimens among HIV-infected women in Italy at time
      of conception: 2001-2011.

PMID- 22663255
TI  - Studying the structural dynamics of bipedal DNA motors with single-molecule
      fluorescence spectroscopy.
AB  - We present a test case example of a detailed single-molecule fluorescence study
      of one of the most sophisticated and complex DNA devices introduced to date, a
      recently published autonomous bipedal DNA motor. We used the diffusion-based
      single-molecule Forster resonance energy transfer technique, coupled to
      alternating laser excitation (sm-FRET-ALEX), to monitor the motor assembly and
      operation. The study included verification of the formation of the correct
      structures, and of the correct motor operation, determination of the formation
      and stepping reaction yields, and identification of side products. Finally, the
      mechanisms of the motor assembly and operation were elucidated by measuring the
      reaction kinetics profile of track-walker binding and of lifting of the walker's
      leg upon fuel addition. The profiles revealed a fast phase, in which about half
      of the reaction was completed, followed by a slow phase which adds somewhat to
      the yield, reflecting the incomplete motor assembly and operation identified in
      the equilibrium experiments. Although further study is needed to fully understand
      the reasons for the incomplete assembly and operation, this work demonstrates
      that single-molecule fluorescence, based on its ability to provide detailed in
      situ structural dynamics information, inaccessible for traditional methods,
      constitutes an excellent tool for chaperoning the development of DNA-based
      technology.

PMID- 22663257
TI  - Mead CompuChem(r).

PMID- 22663256
TI  - Confirmation of hybridity using GISH and determination of 18S rDNA copy number
      using FISH in interspecific F(1) hybrids of Tecoma (Bignoniaceae).
AB  - Interspecific hybridization in  Tecoma  Juss. was conducted to develop novel
      forms for the nursery industry. We report fertile hybrids from the cross T.
      garrocha Hieron. (pistillate parent) * T. stans (L.) Juss. ex Kunth. Leaf
      morphology of the F(1) hybrids of T. garrocha * T. stans was intermediate between
      the parents. GISH also confirmed hybridity. The F(1) hybrids were successfully
      backcrossed to both parents and self-pollinated to produce BC and F(2) progeny. 
      Tecoma garrocha , T. stans, and T. guarume A. DC. 'Tangelo' were self-fertile.
      The F(1) hybrids also were crossed with T. capensis (Thunb.) Lindl. and T.
      guarume 'Tangelo', resulting in three-species hybrids. FISH conducted on F(1)
      hybrids identified four copies of the 18S internal transcribed spacer region.
      Further analysis using FISH has the potential to provide information on the
      evolution of Bignoniaceae and the potential role of polyploidy.

PMID- 22663258
TI  - Racal-decca survey, inc.

PMID- 22663259
TI  - Rockwell international.

PMID- 22663260
TI  - Prior publication problems.

PMID- 22663261
TI  - Foxboro.

PMID- 22663262
TI  - Analyses.

PMID- 22663264
TI  - International.

PMID- 22663263
TI  - Lead research.

PMID- 22663266
TI  - Science.

PMID- 22663265
TI  - Washington.

PMID- 22663267
TI  - States.

PMID- 22663268
TI  - Industry.

PMID- 22663269
TI  - Technology.

PMID- 22663271
TI  - Bioanalytical systems inc.

PMID- 22663270
TI  - New environmental books from acs.

PMID- 22663272
TI  - Crop losses from air pollutants.

PMID- 22663274
TI  - Protecting public groundwater supplies.

PMID- 22663273
TI  - Is this the last word on Love Canal?

PMID- 22663276
TI  - Reagent chemicals.

PMID- 22663275
TI  - Trends in air measurements.

PMID- 22663277
TI  - Environmental auditing.

PMID- 22663279
TI  - O*I*Corporation.

PMID- 22663278
TI  - Fulvic acid: modifier of metal-ion chemistry.

PMID- 22663280
TI  - The definition and use of mixing zones.

PMID- 22663282
TI  - Literature.

PMID- 22663281
TI  - Products.

PMID- 22663285
TI  - Courses.

PMID- 22663283
TI  - Myron L company.

PMID- 22663286
TI  - professional consulting services directory.

PMID- 22663288
TI  - International.

PMID- 22663289
TI  - Classified section * positions open.

PMID- 22663291
TI  - Natal-host environmental effects on juvenile size, transmission success, and
      operational sex ratio in the entomopathogenic nematode Steinernema carpocapsae.
AB  - Trans-host effects can alter the ecological and evolutionary dynamics of parasite
      and host populations. Here, we examine whether resource limitation within a
      parasite's natal host affects propagule size and influences parasite fitness in a
      new host. To alter resource competition, we infected caterpillars with 3 doses of
      the nematode Steinernema carpocapsae and harvested transmission-stage juveniles
      either early or late in the infection. We measured the size of these juveniles,
      and then we examined their ability to colonize and their sex ratio upon maturity
      in a new host. We found a trade-off between the cumulative number and size of
      nematodes emerging from a host. Emerging nematode size declined significantly
      over the time course of the infection, but dose had no significant effects.
      Larger, early emerging nematodes had greater success in colonizing a new host
      than smaller, later emerging nematodes, independently of whether they needed to
      locate the host. Furthermore, although early emerging nematodes resulted in an
      equal sex ratio in the new host, late emerging nematodes resulted in female
      biased populations. These transmission and sex-ratio effects demonstrate that
      conditions in the natal host can affect parasite fitness, and they suggest that
      trans-host effects need to be more fully integrated into our studies of parasite
      populations.

PMID- 22663292
TI  - Introduction. Can comparative effectiveness research help tame rising health care
      costs?

PMID- 22663293
TI  - Can CER be an effective tool for change in the development and assessment of new
      drugs and technologies?
AB  - BACKGROUND: Comparative effectiveness research (CER) has been proposed in the
      United States as a way to compare new drugs and technologies with established
      alternatives and determine not just whether a therapy works, but how well it
      works compared to other options. OBJECTIVES: To define the current use of CER in
      the development of new drugs and technologies and explore what is needed for this
      research approach to reduce or stabilize health care costs in the United States.
      SUMMARY: In 2010, the Patient-Centered Outcomes Research Institute (PCORI) was
      established by the Patient Protection and Affordable Care Act (PPACA) to
      coordinate federally funded CER and recommend research priorities. Hochman and
      McCormick's (2010) evaluation of 328 randomized trials, observational studies,
      and meta-analyses involving medications published between June 2008 and September
      2009 in 6 key journals showed that most published research did not fulfill the
      criteria of CER (defined as comparison to active treatment) and that most study
      design is driven by FDA requirements rather than the need to develop evidence to
      facilitates election of the most effective therapy. Since PPACA provides
      alternative funding for CER, it could encourage funding more studies to help
      determine which treatment delivers the best value per unit of investment from
      clinical, humanistic, and economic perspectives. Manufacturers may avoid CER
      because it increases product development costs, but a drug proven more effective
      is more likely to be accepted by formulary committees, increasing the drug's
      market share, whereas payers may reject or limit use of a new drug that performs
      less effectively in comparative studies. CONCLUSIONS: CER may not directly reduce
      expenditures for drugs and medical technologies. The results may vary widely from
      case to case; however, despite often significantly higher prices for new drugs,
      it is important to look beyond product costs to the overall impact on health care
      costs, including medical cost offsets that may occur through improved health or
      decreased morbidity. To truly decrease cost and improve quality, cost
      effectiveness will have to be integrated into CER with the objective of
      prioritizing efficient therapies in the real-world health care system. If the
      methods and output of CER improve, the resulting cost-effectiveness ratios will
      also be more useful to the payer. CER should ultimately, therefore, be a useful
      tool to help patients, providers, and decision makers provide the most effective
      and most cost-effective interventions.

PMID- 22663295
TI  - Bringing liraglutide to market: a CER case study.
AB  - BACKGROUND: Faced with competition from other drugs and therapies, drug
      manufacturers may be able to use comparative effectiveness research (CER) to help
      reduce barriers to a new drug's adoption and integration into formularies. But
      few examples exist to show how CER can be used effectively and whether the data
      can make a difference. OBJECTIVES: To examine how CER can help strengthen a new
      drug's entry into the market and integration into formularies, and how ongoing
      CER might be valuable as a drug is implemented in the real world. SUMMARY: A
      roundtable of 9 representatives from health plans, including formulary decision
      makers, evaluated how CER in phase 3 development of a new drug can add to the
      drug's strength of evidence, helping decision makers understand how and where to
      integrate that drug into a formulary. The round table participants viewed, as a
      case study, the development of liraglutide, a glucagon-like peptide-1 (GLP-1)
      receptor agonist for adults with type 2 diabetes that was approved by the FDA in
      January 2010. With this drug, CER was incorporated into an extensive type 2
      diabetes clinical development program, comparing how the drug worked in
      comparison with other established therapies. Although there are many antidiabetic
      drugs available for use, patients with type 2 diabetes often need additional
      agents. The FDA approved liraglutide with the conclusion that benefits of the
      drug outweighed potential risks but noted the association with pancreatitis in
      humans and animal data that showed rare medullary thyroid cancer associated with
      liraglutide. Roundtable participants agreed that while pre-launch CER can be
      valuable, ongoing real-world research is also important for confirming expected
      results, identifying additional uses and indications and managing risks. The
      participants also suggested opportunities for additional CER studies and made
      recommendations for manufacturers. CONCLUSIONS: Roundtable thought leaders agreed
      that well-planned trial designs incorporating CER result in high-quality evidence
      that may provide sufficient data to support adoption of a new therapy onto the
      formulary. When more real-world data become available and confirm the phase 3
      clinical trial results, decision makers may be able to use the results to change
      the drug's position and either lessen or extend its use.

PMID- 22663296
TI  - Implementing CER: what will it take?
AB  - BACKGROUND: Comparative effectiveness research (CER) is undeniably changing how
      drugs are developed, launched, priced, and reimbursed in the United States. But
      most organizations are still evaluating what CER can do for them and how and when
      they can utilize the data. A roundtable of stakeholders, including formulary
      decision makers, evaluated CER's possible effects on managed care organizations
      (MCOs) and what it may take to fully integrate CER into decision making.
      OBJECTIVES: To examine the role of CER in current formulary decision making,
      compare CER to modeling, discuss ways CER may be used in the future, and describe
      CER funding sources. SUMMARY: While decision makers from different types of
      organizations, such as pharmacy benefit management (PBM) companies and MCOs, may
      have varying definitions and expectations of CER, most thought leaders from a
      roundtable of stakeholders, including formulary decision makers, see value in
      CER's ability to enhance their formulary decision making. Formulary decision
      makers may be able to use CER to better inform their coverage decisions in areas
      such as benefit design, contracting, conditional reimbursement, pay for
      performance, and other alternative pricing arrangements. Real-world CER will
      require improvement in the health information technology infrastructure to better
      capture value-related information. The federal government is viewed as a key
      driver and funding source behind CER, especially for infrastructure and methods
      development, while industry will adapt the clinical development and create
      increasing CER evidence. CER then needs to be applied to determining value (or
      cost efficacy). CONCLUSIONS: It is expected that CER will continue to grow as a
      valuable component of formulary decision making. Future integration of CER into
      formulary decision making will require federal government and academic
      leadership, improvements in the health information technology infrastructure,
      ongoing funding, and improved and more consistent methodologies.

PMID- 22663297
TI  - Peptide-drug conjugate linked via a disulfide bond for kidney targeted drug
      delivery.
AB  - Chronic kidney disease (CKD) is a worldwide public health problem, and
      unfortunately, the therapeutic index of clinically available drugs is limited.
      Thus, there is a great need to exploit effective treatment strategies, and the
      carrier-drug approach is an attractive method to improve the kidney specificity
      of the therapeutic agents. The aim of this present study is to develop a peptide
      drug conjugate for the kidney targeted delivery of angiotensin-converting enzyme
      (ACE) inhibitor captopril (CAP), since G3-C12 peptide (ANTPCGPYTHDCPVKR) could
      specifically accumulate in the kidney after intravenous injection. Therefore,
      FITC labeled G3-C12 peptide (G3-C12-FITC) and peptide-drug conjugate (G3-C12-CAP)
      with a disulfide bond which can be cleaved by reduced glutathione in the kidney
      were prepared by solid-phase peptide synthesis. The fluorescence imaging of G3
      C12-FITC revealed that the labeled peptide specifically accumulated in the kidney
      soon after i.v. injection to mice, and the accumulation is due largely to the
      reabsorption of the peptide by the proximal renal tubule cells. Furthermore, in
      comparison with the corresponding nonconjugated form, a 2.7-fold increase in
      renal area under concentration-time curve produced by the conjugate was observed
      in mice. Interestingly, the CAP entirely released in the kidney even at 0.05 h
      postinjection through disulfide reduction. As a consequence, the in vivo renal
      ACE inhibition was significantly increased. In conclusion, these findings suggest
      the potential of G3-C12 peptide serving as a suitable candidate carrier for
      kidney-targeted drug delivery. 

PMID- 22663299
TI  - Low-loss, silicon integrated, aluminum nitride photonic circuits and their use
      for electro-optic signal processing.
AB  - Photonic miniaturization requires seamless integration of linear and nonlinear
      optical components to achieve passive and active functions simultaneously. Among
      the available material systems, silicon photonics holds immense promise for
      optical signal processing and on-chip optical networks. However, silicon is
      limited to wavelengths above 1.1 MUm and does not provide the desired lowest
      order optical nonlinearity for active signal processing. Here we report the
      integration of aluminum nitride (AlN) films on silicon substrates to bring active
      functionalities to chip-scale photonics. Using CMOS-compatible sputtered thin
      films we fabricate AlN-on-insulator waveguides that exhibit low propagation loss
      (0.6 dB/cm). Exploiting AlN's inherent Pockels effect we demonstrate electro
      optic modulation up to 4.5 Gb/s with very low energy consumption (down to 10
      fJ/bit). The ultrawide transparency window of AlN devices also enables high speed
      modulation at visible wavelengths. Our low cost, wideband, carrier-free photonic
      circuits hold promise for ultralow power and high-speed signal processing at the
      microprocessor chip level.

PMID- 22663300
TI  - 15N magnetic resonance hyperpolarization via the reaction of parahydrogen with
      15N-propargylcholine.
AB  - (15)N-Propargylcholine has been synthesized and hydrogenated with para-H(2).
      Through the application of a field cycling procedure, parahydrogen spin order is
      transferred to the (15)N resonance. Among the different isomers formed upon
      hydrogenation of (15)N-propargylcholine, only the nontransposed derivative
      contributes to the observed N-15 enhanced emission signal. The parahydrogen
      induced polarization factor is about 3000. The precise identification of the
      isomer responsible for the observed (15)N enhancement has been attained through a
      retro-INEPT ((15)N-(1)H) experiment. T(1) of the hyperpolarized (15)N resonance
      has been estimated to be ca. 150 s, i.e., similar to that reported for the parent
      propargylcholine (144 s). Experimental results are accompanied by theoretical
      calculations that stress the role of scalar coupling constants (J(HN) and J(HH))
      and of the field dependence in the formation of the observed (15)N polarized
      signal. Insights into the good cellular uptake of the compound have been gained.

PMID- 22663298
TI  - Identification and validation of inhibitor-responsive kinase substrates using a
      new paradigm to measure kinase-specific protein phosphorylation index.
AB  - Regulation of all cellular processes requires dynamic regulation of protein
      phosphorylation. We have developed an unbiased system to globally quantify the
      phosphorylation index for substrates of a specific kinase by independently
      quantifying phosphorylated and total substrate molecules in a reverse in-gel
      kinase assay. Non-phosphorylated substrate molecules are first quantified in the
      presence and absence of a specific stimulus. Total substrate molecules are then
      measured after complete chemical dephosphorylation, and a ratio of phosphorylated
      to total substrate is derived. To demonstrate the utility of this approach, we
      profiled and quantified changes in phosphorylation index for Protein Kinase CK2
      substrates that respond to a small-molecule inhibitor. A broad range of inhibitor
      induced changes in phosphorylation was observed in cultured cells. Differences
      among substrates in the kinetics of phosphorylation change were also revealed.
      Comparison of CK2 inhibitor-induced changes in phosphorylation in cultured cells
      and in mouse peripheral blood lymphocytes in vivo revealed distinct kinetic and
      depth-of-response profiles. This technology provides a new approach to facilitate
      functional analyses of kinase-specific phosphorylation events. This strategy can
      be used to dissect the role of phosphorylation in cellular events, to facilitate
      kinase inhibitor target validation studies, and to inform in vivo analyses of
      kinase inhibitor drug efficacy.

PMID- 22663301
TI  - The effect of body mass index and weight change on epithelial ovarian cancer
      survival in younger women: a long-term follow-up study.
AB  - OBJECTIVE: The objective of this study was to assess the relationship between
      body mass index (BMI) and epithelial ovarian cancer survival among young women.
      METHODS: We conducted a cohort analysis of 425 women aged 20-54 years with
      incident epithelial ovarian cancer enrolled during 1980-1982 in Cancer and
      Steroid Hormone (CASH), a population-based, case-control study. Participants'
      vital status was ascertained though linkage with the Surveillance, Epidemiology
      and End Results (SEER) program. Using Cox proportional hazards models, we
      estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the
      association between survival and usual adult BMI, BMI at age 18, and weight
      change from age 18 to adult. RESULTS: During a follow-up of up to 17 years, 215
      women died. Compared to women with an adult BMI in the lowest quartile (<20.7),
      women in the second (20.8-22.5), third (22.6-24.9), and fourth (>=25.0) quartiles
      were not at increased risk for death (HR 1.2, 95% CI 0.8-1.8; HR 1.1, 95% CI 0.7
      1.6; and HR 0.9, 95% CI 0.6-1.4, respectively) (p trend=0.6). Similarly, neither
      age 18 BMI nor weight change were associated with ovarian cancer survival.
      CONCLUSIONS: Although elevated BMI is associated with increased ovarian cancer
      risk among young women, we found no evidence of its association with ovarian
      cancer survival in this population.

PMID- 22663302
TI  - Different rotamer states of cytosine nucleobases in heteronuclear PtPd-, PtPd2,
      and Pt2Pd2Ag complexes derived from [Pt(2,2'-bpy)(1-MeC-N3)2]2+ (1-MeC = 1
      methylcytosine): first examples of species with head-head oriented 1-MeC(-)
      ligands.
AB  - [Pt(2,2'-bpy)(1-MeC-N3)(2)](NO(3))(2) (1) (2,2'-bpy = 2,2'-bipyridine; 1-MeC = 1
      methylcytosine) exists in water in an equilibrium of head-tail and head-head
      rotamers, with the former exceeding the latter by a factor of ca. 20 at room
      temperature. Nevertheless, 1 reacts with (en)Pd(II) (en = ethylenediamine) to
      give preferentially the dinuclear complex [Pt(2,2'-bpy)(1-MeC(-)
      N3,N4)(2)Pd(en)](NO(3))(2).5H(2)O (2) with head-head arranged 1-methylctosinato
      (1-MeC(-)) ligands and Pd being coordinated to two exocyclic N4H(-) positions.
      Addition of AgNO(3) to a solution of 2 leads to formation of a pentanuclear chain
      compound [{Pt(2,2'-bpy)(1-MeC(-))(2)Pd(en)}(2)Ag](NO(3))(5).14H(2)O (5) in which
      Ag(+) cross-links two cations of 2 via the four available O2 sites of the 1-MeC(
      ) ligands. 2 and 5 appear to be the first X-ray structurally characterized
      examples of di- and multinuclear complexes derived from a Pt(II) species with two
      cis-positioned cytosinato ligands adopting a head-head arrangement. (tmeda)Pd(II)
      (tmeda = N,N,N',N'-tetramethylethylenediamine) and (2,2'-bpy)Pd(II) behave
      differently toward 1 in that in their derivatives the head-tail orientation of
      the 1-MeC(-) nucleobases is retained. In [Pt(2,2'-bpy)(1-MeC(-))(2){Pd(2,2'
      bpy)}(2)](NO(3))(4).10H(2)O (4), both (2,2'-bpy)Pd(II) entities are pairwise
      bonded to N4H(-) and O2 sites of the two 1-MeC(-) rings, whereas in [Pt(2,2'
      bpy)(1-MeC(-))(2){Pd(tmeda)}(2)(NO(3))](NO(3))(3).5H(2)O (3) only one of the two
      (tmeda)Pd(II) units is chelated to N4H(-) and O2. The second (tmeda)Pd(II) is
      monofunctionally attached to a single N4H(-) site. On the basis of these
      established binding patterns, ways to the formation of mixed Pt/Pd complexes and
      possible intermediates are proposed. The methylene protons of the en ligand in 2
      are special in that they display two multiplets separated by 0.64 ppm in the (1)H
      NMR spectrum.

PMID- 22663303
TI  - Delivery to mitochondria: a narrower approach for broader therapeutics.
AB  - INTRODUCTION: Research has revealed a relationship between mitochondrial
      dysfunction and diseases such as diabetes, ischemia-reperfusion injury, cancer
      and many more. As a result, mitochondria have gained attention as a target
      organelle for the treatment of many diseases. Successful delivery of the drug
      molecule to the mitochondria could be achieved by keeping in mind the normal
      intracellular trafficking fate of molecules in cell as well as through the
      mitochondria and exploring the new possibilities to reach the target in an
      efficient manner. AREAS COVERED: This review covers important areas such as
      structure and physiology of mitochondria, mitochondrial genome and its role in
      the diseases led by mitochondrial dysfunction, generation of reactive oxygen
      species and its disbalance in pathophysiological conditions and apoptosis.
      Further, the review focuses on various human mitochondrial diseases, particularly
      cancer, and strategies and methods of targeting drug and genetic materials to
      mitochondria. Novel nanotechnology-based carriers for mitochondria delivery are
      discussed with an attempt of providing readers with a current and future
      prospective of mitochondrial therapeutics. EXPERT OPINION: Numerous investigators
      have attempted to establish a mitochondrial drug delivery system; still, many
      hurdles yet remain to be overcome before mitochondrial medicine reaches clinical
      applications. We need to develop a delivery system to encapsulate drugs, proteins
      and genes that would be practically viable for scale-up and strategies to target
      and regulate drug release to the cytosol after endosomal escape, and thereafter
      to deliver the released drug to the mitochondria. Current innovations in the
      nanotechnology could be effectively utilized with mitochondrial medicine for
      designing optimal nanoparticle drug delivery system for mitochondrial diseases on
      clinical setting.

PMID- 22663304
TI  - Iodine-deficiency-induced long lasting angiogenic reaction in thyroid cancers
      occurs via a vascular endothelial growth factor-hypoxia inducible factor-1
      dependent, but not a reactive oxygen species-dependent, pathway.
AB  - BACKGROUND: In the thyroid, iodine deficiency (ID) induces angiogenesis via a
      tightly controlled reactive oxygen species (ROS)-hypoxia inducible factor-1 (HIF
      1)-vascular endothelial growth factor (VEGF) dependent pathway (ROS-HIF-VEGF).
      Deficient iodine intake may be associated with increased thyroid cancer
      incidence. The hypothesis of this work is to test whether ID affects the
      angiogenic processes in thyroid malignant cells by altering the ROS-HIF-VEGF
      pathway. METHODS: Goiters were obtained in RET/PTC3 transgenic and wild-type (wt)
      mice and ID was induced in three thyroid carcinoma cell lines (TPC-1, 8305c, and
      R082-w1). Thyroid blood flow, VEGF mRNA and protein, and HIF-1alpha protein
      expression were measured. The role of HIF-1 and of ROS was assessed using
      echinomycin and N-acetylcysteine (NAC), respectively. RESULTS: The goitrogen
      treatment increased the thyroid blood flow in wt and RET/PTC3 mice. Compared with
      wt mice, basal VEGF expression was higher in RET/PTC3 mice and increased with
      goitrogen treatment. In the three cell lines, ID induced marked increases in VEGF
      mRNA, and moderate increases in HIF-1alpha protein expression that were not
      transient as in normal cells. ID-induced VEGF mRNA expression was fully (8305c),
      partially (TPC-1), or not (R082-w1) blocked by echinomycin. NAC had no effect on
      ID-induced VEGF mRNA and HIF-1alpha protein expression in the three cell lines.
      CONCLUSIONS: ID induces a long lasting angiogenic phenotype in thyroid cancer
      cells that occurs through VEGF induction via a pathway partially mediated by HIF
      1, but not by ROS. These results suggest that, in contrast with normal cells, ID
      induced angiogenesis in cancer cells occurs via alternative and likely less
      controlled routes, thereby leading to uncontrolled growth.

PMID- 22663305
TI  - We'll miss you Steve: how the death of a technology innovator emotionally impacts
      those who use and love his digital devices.
AB  - The death of Apple co-founder Steven Jobs was accompanied by a period of public
      mourning. Reflections shared by both those he knew and those who were connected
      to him through the devices he pioneered were imbued with expressions of loss. The
      goal of the present research was to understand the grieving of those who knew
      Jobs through his devices, as a way of exploring how interpersonal emotions are
      shaped by relationships with technology. The findings from three studies
      conducted in the weeks after Jobs' death indicated demographic variability in
      mourning across the general population, suggesting that many people were more
      deeply affected by his passing. Latter studies highlighted the motivational
      factors that are related to the use of the Apple devices which were at play in
      shaping feelings of sadness and loss.

PMID- 22663306
TI  - Impulsivity in internet addiction: a comparison with pathological gambling.
AB  - Internet addiction has been considered to be associated with poor impulse
      control. The aim of this study is to compare the trait impulsivity of those
      suffering from Internet addiction with that of individuals suffering from
      pathological gambling. Twenty-seven patients diagnosed with Internet addiction
      (age: 24.78+/-4.37 years), 27 patients diagnosed with pathological gambling (age:
      25.67+/-3.97 years), and 27 healthy controls (age: 25.33+/-2.79 years) were
      enrolled in this study. All patients were men seeking treatment. Trait
      impulsivity and the severity of the Internet addiction and pathological gambling
      were measured by the Barratt Impulsiveness Scale-11, the Young's Internet
      Addiction Test, and the South Oaks Gambling Screen, respectively. The Beck
      Depression Inventory and the Beck Anxiety Inventory were also administered to all
      subjects. Our results show that those suffering from Internet addiction showed
      increased levels of trait impulsivity which were comparable to those of patients
      diagnosed with pathological gambling. Additionally, the severity of Internet
      addiction was positively correlated with the level of trait impulsivity in
      patients with Internet addiction. These results state that Internet addiction can
      be conceptualized as an impulse control disorder and that trait impulsivity is a
      marker for vulnerability to Internet addiction.

PMID- 22663308
TI  - Is it time to actively look for vasa praevia?
AB  - Vasa praevia can cause acute severe fetal haemorrhage prior to or during rupture
      of the membranes, contributing to perinatal morbidity and mortality. There are no
      large prospective studies relating to vasa praevia and there is no place for a
      randomised controlled trial as it would be ethically unjustifiable given the poor
      prognosis. There are no national guidelines for the management of vasa praevia.
      Identification of vasa praevia by the 3rd trimester of pregnancy warrants the
      offer of delivery by planned caesarean section to avoid the complications. This
      is essentially intuitive and logical rather than based on any randomised trials.
      A universal screening programme for vasa praevia is not currently supported by a
      robust evidence base; however, the role of prenatal diagnosis requires an
      informed debate, as high quality data may not be forthcoming, given the low
      evidence of the condition. Increasing awareness and understanding of the clinical
      situations can accumulate information, which identify and treat this tragic
      complication of childbirth.

PMID- 22663309
TI  - A successful pregnancy in a Turner syndrome with oocyte donation.
AB  - Advances in reproductive medicine using oocyte donation have made it possible for
      women with Turner syndrome (TS) to achieve successful pregnancies. These
      pregnancies carry substantial fetal and maternal risks, with hypertensive
      disorders or pregnancy and fetal growth restriction common, and an increased risk
      of aortic dissection, sometimes fatal, for the woman. Careful prepregnancy
      assessment and fetal and maternal vigilance during pregnancy is a necessary
      prerequisite for a successful outcome. We present a case of a woman with Turner
      syndrome achieving a successful pregnancy from donor oocyte and review the
      relevant literature.

PMID- 22663310
TI  - Pregnancy outcome among women universally screened for gestational diabetes
      mellitus with a lime-flavoured drink.
AB  - We performed a prospective study involving 400 consecutive pregnant patients to
      determine whether the administration of a lime-flavoured glucose drink followed
      by a blood test 1 h later was a better method of screening for gestational
      diabetes (GDM) than the use of selective screening based on risk factors
      (maternal age over 30 years, East Indian ancestry and obesity). Complete data
      were available for 388 women, 76 were screen positive (1 h blood glucose >= 140
      mg/dl) and GDM was diagnosed in 42 (using a 75 g oral glucose tolerance test)
      giving a positive predictive value of 55%. Selective screening applied to the
      same population would have identified only 34 cases, eight fewer with GDM. In
      this population, the use of the lime-flavoured glucose drink detected
      approximately 25% more cases of GDM than selective screening based on risk
      factors. Caesarean sections were performed in 18 (42.8%) of women with
      gestational diabetes. None of the four perinatal deaths was observed among the
      women with gestational diabetes.

PMID- 22663311
TI  - Specialised fetal and maternal service: outcome of pre-gestational diabetes.
AB  - The objective of the study was to determine the outcome of pregnancies with pre
      gestational diabetes mellitus (PGDM) in the presence of a specialised maternal
      and fetal service. Prospective data included mothers with documented pre
      gestational diabetes (PGDM) delivered between 1 January 2007 and 31 December
      2009. A total of 138 patients with PGDM were included in this study. The post
      lunch glucose level at 34 weeks was significantly lower than at 30 weeks'
      gestation (p =0.007) and 37 weeks' gestation (p =0.02). No correlation was
      observed between maternal blood sugar and birth weight. The incidence of pre-term
      labour, stillbirth and admission to the NICU was similar to the control group.
      Caesarean section rate was 39.1%, and the main indication was previous caesarean
      section. The incidence of fetal anomalies was significantly higher than in the
      control group. It was concluded that the presence of specialised maternal and
      fetal clinics reduces complications related to prenatal glycaemic control.
      However, complications related to preconception care remains high.

PMID- 22663312
TI  - Physical activity during pregnancy in normal-weight and obese women: compliance
      using pedometer assessment.
AB  - The objectives of this prospective study were to compare physical activity in 70
      normal-weight women with a body mass index (BMI) 20-25 kg/m(2), and 70 obese with
      a BMI >= 30 kg/m(2), before and during pregnancy, and to compare compliance using
      the pedometer. Physical activity before pregnancy was assessed by questionnaires
      and during pregnancy by a pedometer worn on 7 consecutive days every 4th week.
      Obese women were less physically active than normal-weight women both before (p
      <0.05) and during pregnancy (p <0.0012). Both the compliance and the physical
      activity gradually declined during gestation. The change in physical activity
      could be described by a significant interaction between BMI group, gestational
      age (p <0.007) and the day of the week (p <0.001) when using ANOVA and
      interaction analysis. Maternal weight gain was larger in the normal-weight than
      in the obese women, but lower in the non-compliant obese women compared with the
      compliant (p <0.05).

PMID- 22663313
TI  - Clinical manifestations of obstructive sleep apnoea in pregnancy: more than
      snoring and witnessed apnoeas.
AB  - Sleep disordered breathing and its symptoms have been associated with a multitude
      of fetal and maternal complications including gestational hypertensive disorders,
      gestational diabetes and possibly pre-term labour and other markers of
      alterations in fetal wellbeing. The disease remains underdiagnosed in the general
      population but likely also in pregnancy, mostly because providers do not
      appropriately screen for the disorder. Sleep disordered breathing may manifest
      differently in women, since women report more fatigue and less snoring than men
      do. This paper discusses typical presentations of sleep disordered breathing but
      also reports some less obvious presentations to help providers recognise those
      manifestations and screen for the disorder when warranted. Our case series
      describes patients with diagnoses such as chronic hypertension, pre-eclampsia,
      pulmonary hypertension, nocturnal asthma and panic attacks, who were diagnosed
      with sleep disordered breathing and offered treatment with CPAP during pregnancy.

PMID- 22663314
TI  - Ponderal index (PI) vs birth weight centiles in the low-risk primigravid
      population: which is the better predictor of fetal wellbeing?
AB  - Our objective was to compare Ponderal index (PI) with birth weight centiles as
      predictors of perinatal morbidity and to determine which best reflects the
      presence of placental disease. We prospectively recruited 1,011 low-risk
      primigravidas and calculated PI and birth weight centiles following delivery.
      Perinatal morbidity was defined as: pre-term birth (PTB); fetal acidosis; an
      Apgar score <7 at 5 min or neonatal resuscitation. Placental disease was defined
      as chronic uteroplacental insufficiency (CUPI); villous dysmaturity; infection or
      vascular pathology. Ponderal index was statistically reduced (25.33 vs 27.79 p
      =0.001) and the incidence of infant birth weight <9th centile was statistically
      higher (11.1% vs 5.1%; p =0.004) in cases with PTB and in CUPI (26.23 vs 27.84; p
      =0.001 and 28.2.1% vs 10.4%; p =0.002). Both PI and infant birth weight centile
      <9th centile for gestational age correlate with PTB, however overall, both are
      poor predictors of neonatal and placental disease.

PMID- 22663315
TI  - The role of cervical ultrasound screening in determining the timing of emergency
      cerclage.
AB  - The present study aimed to determine the outcome of emergency cerclage depending
      on clinical presentation. Retrospective analysis of non-elective cerclage divided
      by clinical presentation: (1) bulging membranes with symptoms (n =19); (2)
      bulging membranes without symptoms (n =13); (3) asymptomatic ultrasound indicated
      were cerclage (n =23). Data from Group 1 and Group 2 were analysed
      retrospectively for average prolongation of pregnancy and delivery before 32
      weeks. Average prolongation of pregnancy (suture to delivery interval) was
      significantly shorter in the group with symptoms compared with the group without
      symptoms (43 vs 89, p <0.01). Delivery before 32 weeks was also significantly
      higher in the group with symptoms compared with the group without symptoms (79%
      vs 31%, p <0.05). Emergency and ultrasound indicated cerclage are best performed
      prior to symptoms. Women at high risk of pre-term birth may benefit from
      transvaginal ultrasound surveillance.

PMID- 22663316
TI  - Planned conservative management of placenta percreta.
AB  - Placenta percreta were traditionally managed by immediate hysterectomy. Between
      2004 and 2010, eight suspected cases of placenta previa accreta/percreta at our
      unit have been managed in a standardised way, with a plan to leave the placenta
      in situ if it does not separate easily. The placenta was removed with minimal
      difficulty in three cases. In two cases of percreta without bladder invasion,
      hysterectomy was performed with the placenta still attached to the uterus. In
      three cases of percreta with bladder invasion, the entire placenta was left in
      situ. In two of these cases, resolution occurred over an 8 and 12 month' period,
      respectively but in the third, the postoperative course was complicated by DVT
      and DIC. This patient then underwent hysterectomy with preoperative uterine
      artery embolisation, inferior vena cava filter placement and ureteric stenting.
      Conservative management is an attractive and safe alternative but careful patient
      selection and individualisation is needed.

PMID- 22663317
TI  - Increased elective caesarean section rate is not associated with a decreased
      serious morbidity rate for twins >= 32 weeks' gestation.
AB  - To assess neonatal and maternal morbidity in twins >= 32 weeks' gestation,
      related to the changes in planned mode of delivery, a retrospective cohort study
      was performed, including 185 twin births delivered in the Atrium Medical Centre,
      Heerlen, during the years 2003-2008. The results were compared with those of an
      earlier study from our department during the period 1999-2002. Compared with the
      1999-2002 cohort, the elective caesarean section rate significantly increased
      from 17.7% to 36.8%. The secondary caesarean rate significantly decreased from
      15.9% to 8.8%, but increased from 1.2% to 3.3% for only twin B. No significant
      differences in serious neonatal morbidity rates for twins A and B were found
      between both study periods, neither in the elective caesarean group, nor in the
      planned vaginal birth group. Serious maternal morbidity was not significantly
      increased in both groups compared with the 1999-2002 cohort.

PMID- 22663318
TI  - Feasibility of using microbiology diagnostic tests of moderate or high complexity
      at the point - of - care in a delivery suite.
AB  - Point-of-care testing (POCT) is one of the fastest growing sectors of laboratory
      diagnostics. Most tests in routine use are haematology or biochemistry tests that
      are of low complexity. Microbiology POCT has been constrained by a lack of tests
      that are both accurate and of low complexity. We describe our experience of the
      practical issues around using more complex POCT for detection of Group B
      streptococci (GBS) in swabs from labouring women. We evaluated two tests for
      their feasibility in POCT: an optical immune assay (Biostar OIA Strep B,
      Inverness Medical, Princetown, NJ) and a PCR (IDI-Strep B, Cepheid, Sunnyvale,
      CA), which have been categorised as being of moderate and high complexity,
      respectively. A total of 12 unqualified midwifery assistants (MA) were trained to
      undertake testing on the delivery suite. A systematic approach to the
      introduction and management of POC testing was used. Modelling showed that the
      probability of test results being available within a clinically useful timescale
      was high. However, in the clinical setting, we found it impossible to maintain
      reliable availability of trained testers. Implementation of more complex POC
      testing is technically feasible, but it is expensive, and may be difficult to
      achieve in a busy delivery suite.

PMID- 22663319
TI  - Assessment of the mobility of mothers postpartum to identify those at greatest
      risk of venous thromboembolism.
AB  - Our aim was to directly assess the postnatal mobility of mothers and to relate
      and compare venous thromboembolism (VTE) risk with current guidelines on VTE
      thromboprophylaxis postpartum. VTE still remains one of the leading causes of
      direct maternal deaths in the western world and this risk is greatest in the
      postnatal period. Mode of delivery and postnatal mobility are key, however the
      effect of the former on the latter is unclear. A total of 200 antenatal women
      were recruited into the study. Each was given a pedometer and recorded the number
      of steps taken daily for 7 days postpartum. A total of 72 women completed the
      study. Those who underwent any form of vaginal delivery were mobile soonest. By
      day 7 postpartum, women following vaginal delivery were almost twice as mobile as
      those who underwent caesarean section (CS). Women who underwent emergency CS were
      more mobile than those who had elective CS, which is contrary to current
      assumptions.

PMID- 22663320
TI  - Is premature ovarian ageing a cause of unexplained recurrent miscarriage?
AB  - Recurrent miscarriage is often unexplained. In our study, we test the hypothesis
      that unexplained recurrent miscarriage is associated with premature ovarian
      ageing by comparing the basal follicle-stimulating hormone (FSH) level between
      women with recurrent miscarriage and a control group of subjects in two different
      ethnic centres: one in Guangzhou, China and the other in Sheffield, UK. The
      subjects were stratified into three different age groups, and all of them were
      under the age of 40 years. We found no significant difference in basal FSH level
      between the subjects and the control groups, and the proportion of women with
      high FSH (>10 IU/l) was higher in the Guangzhou cohort but not in the Sheffield
      cohort. Our observation suggests that premature ovarian ageing is not a
      significant contributory factor of recurrent miscarriage, but a study on the
      ethnic variation in the aetiology of recurrent miscarriage is needed.

PMID- 22663321
TI  - The effects of ischaemic preconditioning on ovarian apoptosis and p53 expression
      during laparoscopy.
AB  - We aimed to explore the effects of ischaemic preconditioning (IP) used to reduce
      ischaemic injury during laparoscopy on ovarian apoptosis and p53 expression. A
      total of 32 rats were randomly allocated into four groups consisting of eight in
      each as follows: Group I was subjected to a sham operation without
      pneumoperitoneum (Pp). Group II was subjected to 5 min of Pp with 15 mmHg
      pressure of CO(2) followed immediately by 5 min of deflation, after that, 60 min
      of Pp and deflation. Group III was subjected to 10 min of Pp and deflation. Group
      IV was subjected to 60 min of Pp and deflation. The ovarian tissues were
      histologically and immunohistochemically processed. The number of apoptotic and
      p53(+) cells were measured. All the data revealed that ovarian apoptosis and p53
      expression were highest in group IV. Apoptotic cells and p53(+) cells were lower
      in IP groups. Additionally, group II had significantly lower p53(+) cells
      compared with group III. Pp induces higher amount of apoptosis and p53 expression
      in ovary but preconditioning may have protective effects during laparoscopy.
      Furthermore, 5 min of preconditioning may be more effective. Therefore, the
      effects of Pp and preconditioning should be considered for the ovary during
      laparoscopy.

PMID- 22663322
TI  - Ovarian ectopic pregnancy: aetiology, diagnosis, and challenges in surgical
      management.
AB  - Primary ovarian ectopic pregnancy (OEP) remains a rare but important type of
      ectopic pregnancy which is normally diagnosed at surgery. The aetiology is
      unknown. We have found fertility treatments (18.1%) and intrauterine
      contraceptive devices (19.3%) remain important associated risk factors. We
      undertook a world literature review of all cases since 1995. We found that 52% of
      cases were managed laparoscopically, which is less than the reported UK rate of
      all ectopics, of 85.9%. Over that time period, eight patients were treated
      medically with a success rate of 50%. While the original 1878 Spiegelberg's
      criterion still holds for the diagnosis, the addition of modern ultrasound
      scanning has made a radiological diagnosis possible. In a few cases, the
      management of OEP remains similar to that of a tubal ectopic pregnancy with the
      same challenges. Laparoscopy with ovarian sparing in the stable woman is today
      the surgical treatment of choice.

PMID- 22663323
TI  - Hyperemesis gravidarum and fetal gender: a retrospective study.
AB  - This retrospective study of 9,980 women who delivered at the James Paget
      Hospital, Norfolk, UK, over 5 years, aimed to primarily determine whether the
      incidence of hyperemesis gravidarum (HG) is higher in the presence of a female
      fetus. The results showed that more women with HG had a female fetus compared
      with women without HG. Also found was that heavy ketonuria was more prevalent in
      women with a female fetus compared with women with a male fetus, and the mean
      number of admissions per woman was also higher in women with a female fetus
      compared with women with a male fetus. It can be concluded that women presenting
      with HG are more likely to have a female fetus and that women with HG and a
      female fetus tend to a higher level of ketonuria and an increased number of
      hospital admissions.

PMID- 22663324
TI  - Accuracy of frozen section in the diagnosis of ovarian tumours.
AB  - The purpose of our retrospective study was to assess the accuracy of
      intraoperative frozen section diagnosis compared to final paraffin diagnosis in
      ovarian tumours at a gynaecological oncology centre in the UK. We analysed 66
      cases and observed that frozen section consultation agreed with final paraffin
      diagnosis in 59 cases, which provided an accuracy of 89.4%. The overall
      sensitivity and specificity for all tumours were 85.4% and 100%, respectively.
      The positive predictive value (PPV) and negative predictive value (NPV) were 100%
      and 89.4%, respectively. Of the seven cases with discordant results, the majority
      were large, mucinous tumours, which is in line with previous studies. Our study
      demonstrated that despite its limitations, intraoperative frozen section has a
      high accuracy and sensitivity for assessing ovarian tumours; however, care needs
      to be taken with large, mucinous tumours.

PMID- 22663325
TI  - Non-Hodgkin lymphoma during the 1st trimester of pregnancy.

PMID- 22663327
TI  - Second trimester intracranial fetal teratoma.

PMID- 22663326
TI  - Management of precursor B-lymphoblastic lymphoma/leukaemia of thoracic spine in a
      pregnancy presenting with acute paraplegia.

PMID- 22663328
TI  - Carbamazepine use in pregnancy and coincidental thalidomide-like phocomelia in a
      newborn.

PMID- 22663329
TI  - Unilateral focal renal artery stenosis complicated by early onset superimposed
      pre-eclampsia.

PMID- 22663330
TI  - Successful pregnancy in a woman with liver cirrhosis complicated by recurrent
      variceal bleeding.

PMID- 22663331
TI  - Filshie clip migration: A report of two cases.

PMID- 22663332
TI  - Vaginal trauma after a personal watercraft accident.

PMID- 22663333
TI  - Successful reconstructive surgery to alter distorted vaginal axis causing
      apareunia.

PMID- 22663334
TI  - A case report of a successful live birth following IVF preceded by fertility
      sparing surgery for a large adenomyomata.

PMID- 22663335
TI  - A massive haemorrhage caused by rupture of cystic cervical endometriosis.

PMID- 22663336
TI  - Gestational choriocarcinoma in liver mimicking ruptured ectopic pregnancy.

PMID- 22663337
TI  - Osteoclastic giant cell rich carcinoma cervix: a rare entity.

PMID- 22663338
TI  - Simple treatment options exist for supraventricular tachycardia in pregnancy.

PMID- 22663339
TI  - Maternal arrhythmias detected during labour could be caused by drugs used for
      induction of labour.

PMID- 22663341
TI  - Localization and quantification of drugs in animal tissues by use of desorption
      electrospray ionization mass spectrometry imaging.
AB  - Mass spectrometric imaging (MSI) has emerged as a powerful technique to obtain
      spatial arrangement of individual molecular ions in animal tissues. Ambient
      desorption electrospray ionization (DESI) technique is uniquely suited for such
      imaging experiments, as it can be performed on animal tissues in their native
      environment without prior treatments. Although MSI has become a rapid growing
      technique for localization of proteins, lipids, drugs, and endogenous compounds
      in different tissues, quantification of imaged targets has not been explored
      extensively. Here we present a novel MSI approach for localization and
      quantification of drugs in animal thin tissue sections. DESI-MSI using an
      Orbitrap mass analyzer in full scan mode was performed on 6 MUm coronal brain
      sections from rats that were administered 2.5 mg/kg clozapine. Clozapine was
      localized and quantified in individual brain sections 45 min postdose. External
      calibration curves were prepared by micropipetting standards with internal
      standard (IS) on top of the tissues, and average response factors were calculated
      for the scans in which both clozapine and IS were detected. All response factors
      were normalized to area units. Quantifications from DESI-MSI revealed 0.2-1.2 ng
      of clozapine in individual brain sections, results that were further confirmed by
      extraction and liquid chromatography/tandem mass spectrometry (LC/MS/MS)
      analysis.

PMID- 22663342
TI  - Antifogging and antireflection coatings fabricated by integrating solid and
      mesoporous silica nanoparticles without any post-treatments.
AB  - Antifogging and -reflection coatings were fabricated on glass and poly(methyl
      methacrylate) (PMMA) substrates by integrating solid silica nanoparticles of 25
      nm (S-25) and mesoporous silica nanoparticles (MSNs) of 45 nm via layer-by-layer
      assembly without any post-treatments. Superhydrophilicity and a maximum
      transmittance of 98.5% in the visible spectral range was achieved for the (PDDA/S
      25)4/(PDDA/MSNs) coating deposited on slide glass. The maximum transmittance even
      reached as high as 99.3% in the visible spectral range by applying a coating of
      (PDDA/S-25)8/(PDDA/MSNs) on PMMA substrate. Scanning and transmission electron
      microscopy were used to observe the morphology and structure of nanoparticles and
      coating surfaces. Optical properties were characterized by UV-visible
      spectrophotometer. Surface wettability was studied by a contact angle/interface
      system. The influence of mesopores was also discussed on the transmission and
      wetting properties of coatings. The high porosity of mesoporous nanoparticles and
      loose stacking of solid and mesoporous nanoparticles are considered to
      significantly contribute to the enhancements of both light transmission and
      hydrophilicity. 

PMID- 22663344
TI  - Self-efficacy mediates the impact of craving on smoking abstinence in low to
      moderately anxious patients: results of a moderated mediation approach.
AB  - Little is known about the effect of craving on smoking abstinence among cardiac
      patients who smoked prior to admission and the mechanisms that might facilitate
      success in smoking cessation after discharge from hospital. This study examined
      the mediating effect of self-efficacy on the relationship between craving and
      smoking abstinence and how this mechanism may be contingent on emotional state at
      the time of hospital admission. Cardiac patients who smoked prior to admission
      were recruited from cardiac nursing units in Dutch hospitals. On hospitalization,
      244 patients completed a questionnaire on craving, self-efficacy to smoking
      cessation, and anxiety and depression levels. Six months after discharge patients
      were interviewed to ascertain their smoking status. Simple mediation and
      moderated mediation effects of craving and self-efficacy on smoking abstinence
      were tested. Of the patients who successfully completed the baseline
      questionnaire and the follow-up interview, 38% were not smoking at 6 months. Self
      efficacy mediated the effect of craving on smoking abstinence. However, this
      indirect effect was more pronounced among patients with relatively low to
      moderate anxiety at the time of hospitalization. Our findings suggest that
      craving reduces self-efficacy, which in turn reduces the likelihood of smoking
      abstinence, although this process applies only to those patients with low to
      moderate anxiety levels at the time of hospitalization. Interventions for smoking
      cardiac patients should aim to reduce craving and to enhance patients' self
      efficacy to smoking cessation after discharge from hospital.

PMID- 22663345
TI  - Predictive effects of good self-control and poor regulation on alcohol-related
      outcomes: do protective behavioral strategies mediate?
AB  - In the present study, we examined whether use of protective behavioral strategies
      mediated the relationship between self-control constructs and alcohol-related
      outcomes. According to the two-mode model of self-control, good self-control
      (planfulness; measured with Future Time Perspective, Problem Solving, and Self
      Reinforcement) and poor regulation (impulsivity; measured with Present Time
      Perspective, Poor Delay of Gratification, Distractibility) are theorized to be
      relatively independent constructs rather than opposite ends of a single
      continuum. The analytic sample consisted of 278 college student drinkers (68%
      women) who responded to a battery of surveys at a single time point. Using a
      structural equation model based on the two-mode model of self-control, we found
      that good self-control predicted increased use of three types of protective
      behavioral strategies (Manner of Drinking, Limiting/Stopping Drinking, and
      Serious Harm Reduction). Poor regulation was unrelated to use of protective
      behavioral strategies, but had direct effects on alcohol use and alcohol
      problems. Further, protective behavioral strategies mediated the relationship
      between good self-control and alcohol use. The clinical implications of these
      findings are discussed.

PMID- 22663347
TI  - A new molineid (Nematoda: Trichostrongylina) parasite of Dasypus hybridus
      (Xenarthra: Dasypodidae) from Argentina.
AB  - Delicata abbai n. sp. collected from the small intestine of the southern long
      nosed armadillo, Dasypus hybridus, from Argentina is herein described. This new
      species is characterized by vulvar opening within second half of body length,
      female tail conical, ending bluntly with a terminal spine, complex spicules,
      presence of a bursal membrane supported by 2 small rays, and a synlophe with
      bilateral symmetry and 26 cuticular ridges. By the morphology of the caudal
      bursa, caudal end of female, and shape of spicules, the new species resembles
      Delicata cameroni Travassos, 1935 and Delicata variabilis Travassos, 1935 .
      However, it differs from D. cameroni by having rays 5 and 6 diverging more
      proximally, rays 8 shorter than the dorsal ray, and spicules with a different
      shape. Delicata abbai n. sp. is distinguished from D. variabilis mainly by the
      spicules, which have a different shape and proportion of their constitutive
      parts. This is the first report of a species of Delicata in Argentina.

PMID- 22663346
TI  - Integrated cytogenetic, ecological, and DNA barcode study reveals cryptic
      diversity in Simulium (Gomphostilbia) angulistylum (Diptera: Simuliidae).
AB  - An integrated approach based on cytogenetics, molecular genetics, and ecology was
      used to examine diversity in the black fly Simulium angulistylum Takaoka & Davies
      in Thailand. Cytological analysis revealed three cytoforms (A, B, and C) of S.
      angulistylum differentiated by fixed chromosome inversions. Distributions of
      these cytoforms were associated with ecology. Cytoforms A and B were found in low
      altitude habitats (<600 m above sea level), whereas cytoform C occurred at high
      altitudes (>1000 m above sea level). Mitochondrial DNA sequences of the
      cytochrome oxidase subunit I barcoding region revealed significant genetic
      differentiation among the cytoforms. The mitochondrial DNA haplotype network
      revealed divergent lineages within cytoforms, indicating additional hidden
      diversity. Therefore, integrated approaches are necessary for fully understanding
      black fly biodiversity. Population genetic analysis revealed high genetic
      structuring that could be due to the habitat preferences of S. angulistylum.
      Phylogeographic analyses indicated population demographic expansion at the mid
      Pleistocene (900 000 years ago), which is older than for other black flies and
      insects in the Southeast Asian mainland. The high level of genetic structure and
      diversity, therefore, could also be due to the long demographic history of S.
      angulistylum.

PMID- 22663343
TI  - A developmental perspective on neuroeconomic mechanisms of contingency
      management.
AB  - This paper provides a developmental overview of relevant theory and research on
      delay discounting and neuroeconomics, and their implications for contingency
      management (CM) approaches to treatment. Recent advances in the neuroscience of
      decision making have the potential to inform treatment development for adolescent
      substance use in general, and CM treatments in particular. CM interventions may
      be informed by research on delay discounting, a type of decision making that
      reflects how individuals value immediate versus delayed rewards. Delay
      discounting reliably distinguishes substance abusers from nonabusers and is a
      significant predictor of individual differences in response to substance use
      treatments. Discounting may also be important in predicting response to CM, as CM
      attempts to directly influence this decision-making process, shifting the
      preference from the immediate rewards of use to delayed rewards for choosing not
      to use. Multiple neural processes underlie decision making, and those processes
      have implications for adolescent substance abuse. There are significant
      neurodevelopmental processes that differentiate adolescents from adults. These
      processes are implicated in delay discounting, suggesting that adolescence may
      reflect a period of plasticity in temporal decision making. Understanding the
      neural mechanisms of delay discounting has led to promising working memory
      interventions directly targeting the executive functions that underlie individual
      choices. These interventions may be particularly helpful in combination with CM
      interventions that offer immediate rewards for brief periods of abstinence, and
      may show particular benefit in adolescence due to the heightened neural
      plasticity of systems that underlie temporal discounting in adolescence.

PMID- 22663349
TI  - Managing motivational conflict: how self-esteem and executive resources influence
      self-regulatory responses to risk.
AB  - This article explores how self-esteem and executive resources interact to
      determine responses to motivational conflict. One correlational and 3
      experimental studies investigated the hypothesis that high and low self-esteem
      people undertake different self-regulatory strategies in "risky" situations that
      afford opportunity to pursue competing goals and that carrying out these
      strategies requires executive resources. When such resources are available, high
      self-esteem people respond to risk by prioritizing and pursuing approach goals,
      whereas low self-esteem people prioritize avoidance goals. However, self-esteem
      does not influence responses to risk when executive resources are impaired. In
      these studies, risk was operationalized by exposing participants to a
      relationship threat (Studies 1 and 2), by using participants' self-reported
      marital conflict (Study 3), and by threatening academic competence (Study 4).
      Executive resources were operationalized as cognitive load (Studies 1 and 2),
      working memory capacity (Study 3), and resource depletion (Study 4). When
      executive resources were ample, high self-esteem people responded to
      interpersonal risk by making more positive relationship evaluations (Studies 1,
      2, and 3) and making more risky social comparisons following a personal failure
      (Study 4) than did low self-esteem people. Self-esteem did not predict
      participants' responses when executive resources were impaired or when risk was
      absent. The regulatory function of self-esteem may be more resource-dependent
      than has been previously theorized.

PMID- 22663350
TI  - Disentangling stereotype activation and stereotype application in the stereotype
      misperception task.
AB  - When forming impressions about other people, stereotypes about the individual's
      social group often influence the resulting impression. At least 2 distinguishable
      processes underlie stereotypic impression formation: stereotype activation and
      stereotype application. Most previous research has used implicit measures to
      assess stereotype activation and explicit measures to assess stereotype
      application, which has several disadvantages. The authors propose a measure of
      stereotypic impression formation, the stereotype misperception task (SMT),
      together with a multinomial model that quantitatively disentangles the
      contributions of stereotype activation and application to responses in the SMT.
      The validity of the SMT and of the multinomial model was confirmed in 5 studies.
      The authors hope to advance research on stereotyping by providing a measurement
      tool that separates multiple processes underlying impression formation.

PMID- 22663348
TI  - A novel sustained-release formulation of recombinant human growth hormone and its
      pharmacokinetic, pharmacodynamic and safety profiles.
AB  - An effective and safe formulation of sustained-release rhGH for two months using
      poly(monomethoxypolyethylene glycol-co-D,L-lactide) (mPEG-PLA, PELA) microspheres
      was developed to reduce the frequency of medication. The rhGH-loaded PELA
      microspheres with a narrow size distribution were successfully prepared by a
      double emulsion method combined with a premix membrane emulsification technique
      without any exogenous stabilizing excipients. The narrow size distribution of the
      microspheres would guarantee repeatable productivity and release behavior.
      Moreover, the amphiphilic PELA improved the bioactivity retention of protein
      drugs since it prevented protein contact with the oil/water interface and the
      hydrophobic network, and modulated diffusion of acidic degradation products from
      the carrier system. These PELA microspheres were compared in vivo with commercial
      rhGH solution, conventional poly(D,L-lactic acid) (PLA) and poly(D,L-lactic-co
      glycolic acid) (PLGA) microspheres. Administration of rhGH-PELA could extend the
      duration of rhGH release (for up to 56 days) and increase area under the curve
      (AUC) compared to rhGH solution, PLA or PLGA microspheres in Sprague-Dawley (SD)
      rats. In addition, rhGH-PELA microspheres induced a greater response in total
      insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding
      protein-3 (IGFBP-3) than other rhGH formulations. With a hypophysectomized SD rat
      model, the pharmacological efficacy of rhGH-PELA microspheres was shown to be
      better than that from daily administration of rhGH solutions over 6 days based on
      body weight gain and width of the tibial growth plate. Histological examination
      of the injection sites indicated a significantly milder inflammatory response
      than that observed after injection of PLA and PLGA microspheres. Neither anti
      rhGH antibodies nor the toxic effects on heart, liver and kidney were detectable
      after administration of rhGH-PELA microspheres in SD rats. These results suggest
      that rhGH-PELA microspheres have the potential to be clinically effective and
      safe when administered only once every two months, a dose regimen for better
      patient acceptance and compliance.

PMID- 22663351
TI  - Cognitive sophistication does not attenuate the bias blind spot.
AB  - The so-called bias blind spot arises when people report that thinking biases are
      more prevalent in others than in themselves. Bias turns out to be relatively easy
      to recognize in the behaviors of others, but often difficult to detect in one's
      own judgments. Most previous research on the bias blind spot has focused on bias
      in the social domain. In 2 studies, we found replicable bias blind spots with
      respect to many of the classic cognitive biases studied in the heuristics and
      biases literature (e.g., Tversky & Kahneman, 1974). Further, we found that none
      of these bias blind spots were attenuated by measures of cognitive sophistication
      such as cognitive ability or thinking dispositions related to bias. If anything,
      a larger bias blind spot was associated with higher cognitive ability. Additional
      analyses indicated that being free of the bias blind spot does not help a person
      avoid the actual classic cognitive biases. We discuss these findings in terms of
      a generic dual-process theory of cognition.

PMID- 22663352
TI  - Ultradeformable liposomes with terpenes for delivery of hydrophilic compound.
AB  - Ultradeformable liposomes containing penetration enhancers were created to
      deliver NaFl. Vesicles were investigated for their particle size, zeta potential,
      NaFl entrapment efficiency (%EE), loading efficiency, and in vitro skin
      penetration. The vesicles obtained were spherical in shape, with a particle size
      of less than 100 nm and a negative surface charge (-6 to -11 mV). The %EE of NaFl
      loaded in vesicles ranged from 37 to 48%. Ultradeformable liposomes with
      monoterpenes (d-limonene, 1,8-cineole and geraniol) significantly improved NaFl
      penetration through the skin. Confocal laser scanning microscopy analysis
      confirmed skin-penetration results and was used to evaluate the behavior of
      hydrophilic compounds penetrating through the skin.

PMID- 22663353
TI  - Systematic approach to design organic magnetic molecules: strongly coupled
      diradicals with ethylene coupler.
AB  - The intramolecular magnetic coupling constant (J) values of diradical systems
      linked with two monoradicals through a coupler (para-substituted phenyl acetylene
      (Model I), meta-substituted phenyl acetylene (Model II), ethylene (Model III))
      were investigated by unrestricted density functional theory calculations. We
      divided eight monoradicals into alpha-group and beta-group according to Mulliken
      spin density values of the connected atoms. The overall trends in the strength of
      magnetic interactions of diradicals were found to be identical in three different
      model systems. The diradicals with para-substituted phenyl acetylene coupler
      resulted in almost twice stronger intramolecular magnetic coupling interactions
      of the corresponding diradicals as compared to the meta-substituted one with
      opposite magnetism. NN-Ethylene-PO (nitronyl nitroxide radical coupled to
      phenoxyl radical via ethylene coupler) was calculated to have the strongest
      magnetic coupling constant with ferromagnetism, and to be even stronger (more
      than twice) than NN-ethylene-NN (nitronyl nitroxide diradical with ethylene
      coupler), which was reported to have strong antiferromagnetic interactions in a
      previous experiment. It was found that the spin density values of the connected
      atoms are closely related to the determination of magnetic interactions and J
      values. The spin states of the ground state in diradical systems were explained
      by means of the spin alternation rule.

PMID- 22663354
TI  - Mapping the protein domain structures of the respiratory mucins: a mucin proteome
      coverage study.
AB  - Mucin genes encode a family of the largest expressed proteins in the human
      genome. The proteins are highly substituted with O-linked oligosaccharides that
      greatly restrict access to the peptide backbones. The genomic organization of the
      N-terminal, O-glycosylated, and C-terminal regions of most of the mucins has been
      established and is available in the sequence databases. However, much less is
      known about the fate of their exposed protein regions after translation and
      secretion, and to date, detailed proteomic studies complementary to the genomic
      studies are rather limited. Using mucins isolated from cultured human airway
      epithelial cell secretions, trypsin digestion, and mass spectrometry, we
      investigated the proteome coverage of the mucins responsible for the maintenance
      and protection of the airway epithelia. Excluding the heavily glycosylated mucin
      domains, up to 85% coverage of the N-terminal region of the gel-forming mucins
      MUC5B and MUC5AC was achieved, and up to 60% of the C-terminal regions were
      covered, suggesting that more N- and sparsely O-glycosylated regions as well as
      possible other modifications are available at the C-terminus. All possible
      peptides from the cysteine-rich regions that interrupt the heavily glycosylated
      mucin domains were identified. Interestingly, 43 cleavage sites from 10 different
      domains of MUC5B and MUC5AC were identified, which possessed a non-tryptic
      cleavage site on the N-terminal end of the peptide, indicating potential exposure
      to proteolytic and/or "spontaneous cleavages". Some of these non-tryptic
      cleavages may be important for proper maturation of the molecule, before and/or
      after secretion. Most of the peptides identified from MUC16 were from the SEA
      region. Surprisingly, three peptides were clearly identified from its heavily
      glycosylated regions. Up to 25% coverage of MUC4 was achieved covering seven
      different domains of the molecule. All peptides from the MUC1 cytoplasmic domain
      were detected along with the three non-tryptic cleavages in the region. Only one
      peptide was identified from MUC20, which led us to successful antisera raised
      against the molecule. Taken together, this report represents our current efforts
      to dissect the complexities of mucin macromolecules. Identification of regions
      accessible to proteolysis can help in the design of effective antibodies and
      points to regions that might be available for mucin-protein interactions and
      identification of cleavage sites will enable understanding of their pre- and post
      secretory processing in normal and disease environments.

PMID- 22663355
TI  - Rapid synthesis of radioactive transition-metal carbonyl complexes at ambient
      conditions.
AB  - Carbonyl complexes of radioactive transition metals can be easily synthesized
      with high yields by stopping nuclear fission or fusion products in a gas volume
      containing CO. Here, we focus on Mo, W, and Os complexes. The reaction takes
      place at pressures of around 1 bar at room temperature, i.e., at conditions that
      are easy to accommodate. The formed complexes are highly volatile. They can thus
      be transported within a gas stream without major losses to setups for their
      further investigation or direct use. The rapid synthesis holds promise for
      radiochemical purposes and will be useful for studying, e.g.,  chemical
      properties of superheavy elements.

PMID- 22663356
TI  - Dionex the ion experts.

PMID- 22663357
TI  - Sludge on land.

PMID- 22663358
TI  - Waste at sea.

PMID- 22663359
TI  - Seastar instruments ltd.

PMID- 22663360
TI  - Disinfection and indicator organisms.

PMID- 22663362
TI  - States.

PMID- 22663361
TI  - To order american chemical society primary publications.

PMID- 22663364
TI  - Washington.

PMID- 22663363
TI  - International.

PMID- 22663365
TI  - Fellowship.

PMID- 22663366
TI  - Technology.

PMID- 22663367
TI  - Business.

PMID- 22663369
TI  - EPA's air quality bubble revisited.

PMID- 22663368
TI  - Spent liquors from pulp bleaching.

PMID- 22663370
TI  - State of the environment 1984.

PMID- 22663371
TI  - The Electric Power Research Institute's.

PMID- 22663372
TI  - Environmental program for Philadelphia.

PMID- 22663373
TI  - Recent advances in monitoring air pollution.

PMID- 22663374
TI  - Health effects of low-level exposures.

PMID- 22663375
TI  - Products.

PMID- 22663377
TI  - professional consulting services directory.

PMID- 22663376
TI  - Literature.

PMID- 22663378
TI  - Classified section.

PMID- 22663380
TI  - Cell surface-anchored fluorescent aptamer sensor enables imaging of chemical
      transmitter dynamics.
AB  - A fluorescent aptamer sensor was applied to the analysis of extracellular
      chemical transmitter dynamics. We utilized a tocopherol-labeled aptamer, which
      allowed the direct anchoring of the fluorescent aptamer on the cell surface while
      retaining its performance as a fluorescent sensor. The fast-responsive
      fluorescent DNA aptamer sensor, which targets adenine compounds, was anchored on
      the surface of brain astrocytes. Fluorescence imaging of the aptamer-anchored
      astrocytes enabled the real-time monitoring of release of adenine compounds as a
      gliotransmitter, which was synchronized with calcium wave propagation in
      neighboring cells.

PMID- 22663381
TI  - Removal of surface states and recovery of band-edge emission in InAs nanowires
      through surface passivation.
AB  - Surface states in semiconductor nanowires (NWs) are detrimental to the NW optical
      and electronic properties and to their light emission-based applications, due to
      the large surface-to-volume ratio of NWs and the congregation of defects states
      near surfaces. In this paper, we demonstrated an effective approach to eliminate
      surface states in InAs NWs of zinc-blende (ZB) and wurtzite (WZ) structures and a
      dramatic recovery of band edge emission through surface passivation with organic
      sulfide octadecylthiol (ODT). Microphotoluminescence (PL) measurements were
      carried out before and after passivation to study the dominant recombination
      mechanisms and surface state densities of the NWs. For WZ-NWs, we show that the
      passivation removed the surface states and recovered the band-edge emission,
      leading to a factor of ~19 reduction of PL linewidth. For ZB-NWs, the deep
      surface states were removed and the PL peaks width became as narrow as ~250 nm
      with some remaining emission of near band-edge surface states. The passivated NWs
      showed excellent stability in atmosphere, water, and heat environments. In
      particular, no observable changes occurred in the PL features from the passivated
      NWs exposed in air for more than five months.

PMID- 22663382
TI  - Anion-directed formation and degradation of an interlocked metallohelicate.
AB  - Although there are many examples of catenanes, those of more complex mechanically
      interlocked molecular architectures are rare. Additionally, little attention has
      been paid to the degradation of such interlocked systems into their starting
      complexes, although formation and degradation are complementary phenomena and are
      equally important. Interlocked metallohelicate, [(Pd(2)L(4))(2)](8+) (2(8+)), is
      a quadruply interlocked molecular architecture consisting of two mechanically
      interlocked monomers, [Pd(2)L(4)](4+) (1(4+)). 2(8+) has three internal cavities,
      each of which encapsulates one NO(3)(-) ion (1:3 host-guest complex,
      2?(NO(3)|NO(3)|NO(3))(5+)) and is characterized by unusual thermodynamic
      stability. However, both the driving force for the dimerization and the origin of
      the thermodynamic stability remain unclear. To clarify these issues, BF(4)(-),
      PF(6)(-), and OTf(-) have been used to demonstrate that the dimerization is
      driven by the anion template effect. Interestingly, the stability of 2(8+)
      strongly depends on the encapsulated anions (2?(NO(3)|NO(3)|NO(3))(5+) ?
      2?(BF(4)|BF(4)|BF(4))(5+)). The origins of this differing thermodynamic stability
      have been shown through detailed investigations to be due to the differences in
      the stabilization of the interlocked structure by the host-guest interaction and
      the size of the anion. We have found that 2-naphthalenesulfonate (ONs(-)) induces
      the monomerization of 2?(NO(3)|NO(3)|NO(3))(5+) via intermediate
      2?(ONs|NO(3)|ONs)(5+), which is formed by anion exchange. On the basis of this
      finding, and using p-toluenesulfonate (OTs(-)), the physical separation of
      2?(NO(3)|NO(3)|NO(3))(5+) and 1(4+) as OTs(-) salt was accomplished.

PMID- 22663383
TI  - Decorin promotes myogenic differentiation and mdx mice therapeutic effects after
      transplantation of rat adipose-derived stem cells.
AB  - BACKGROUND AIMS: Adipose-derived stem cells (ADSC) have been considered as
      attractive candidates for the treatment of Duchenne muscular dystrophy (DMD), but
      the rate of ADSC myogenesis is very low. Myostatin (Mstn), a negative regulator
      of myogenesis, is known to be responsible for limiting skeletal muscle
      regeneration. Decorin could bind Mstn and deactivate it. Decorin has been shown
      to improve myogenic differentiation in mdx mice. We hypothesized that inhibition
      of Mstn by using decorin may ameliorate myogenic differentiation of ADSC.
      METHODS: Rat ADSC were transfected with the lentivirus-containing green
      fluorescence protein (GFP) and human decorin gene. The transfected ADSC were
      induced by 5-azacytidine (5-AzaC). The rates of myogenic differentiation and
      adipogenesis were detected. The transfected ADSC were injected into mdx mice and
      the expression of Mstn and decorin detected by Western blot. Dystrophin was
      detected after transfected ADSC transplantation by immunofluorescence staining
      and Western blot. Serum creatine kinase (CK) and histologic changes were also
      evaluated. RESULTS: The optimal multiplicity of infection of ADSC was 10. Decorin
      improved muscle mass. In accordance with the increased muscle mass, dystrophin
      expression increased. Following the level of decorin increase, the Mstn
      expression decreased. Furthermore, serum CK and histologic changes in centrally
      nucleated fiber (CNF) decreased. CONCLUSIONS: Improved myogenic differentiation
      of ADSC was observed by using decorin. This process was probably the result of
      decorin inhibiting Mstn. A new method of DMD therapy combining Mstn inhibition
      (using decorin) and ADSC transplantation is probably feasible.

PMID- 22663542
TI  - A feasible way to use carbon nanotubes to deliver drug molecules: transdermal
      application.
AB  - INTRODUCTION: Nanotechnology has gained increasing importance in the
      pharmaceutical and medical fields, beyond its importance in physics and
      technology. Targeting of the drug or active molecules can be achieved rather
      easily with some nanocarriers because of their unique properties; to program or
      control of delivery can also be possible. One of the smart nanosystems is carbon
      nanotubes (CNTs) because they are elecroconductive and they have very big surface
      area to deliver active molecules. There have been many drug delivery systems
      proposed to the scientific world using CNTs. One administration way which appears
      to be the most appropriate for drug delivery is transdermal application. AREAS
      COVERED: Performed experiments and proposed techniques with the use of CNTs are
      scrutinized and discussed in this review. EXPERT OPINION: In the light of current
      knowledge, a feasible way to use CNTs to deliver drug molecules is transdermally.

PMID- 22663543
TI  - Zyflamend, a combination of herbal extracts, attenuates tumor growth in murine
      xenograft models of prostate cancer.
AB  - Prostate cancer (PrC) is the second deadliest cancer of males in the United
      States Hormone deprivation therapy (HDT), a common therapy for advanced forms of
      the disease, results in tumor regression; unfortunately, tumors inevitably become
      castrate-resistant. Diet is not an appropriate primary therapy for refractory
      forms of the disease; however, diet may be effective as an adjuvant to HDT,
      potentially extending the latency period and delaying relapse and/or inhibiting
      refractory growth. Zyflamend(r) is a combination of extracts from multiple herbs,
      each with reported anticancer properties. Zyflamend can inhibit growth of various
      PrC cell lines, but no studies have investigated its potential use in vivo using
      a model of castrate-resistant PrC. In this study, oral doses of Zyflamend at
      human equivalent doses inhibited androgen-dependent and castrate-resistant tumor
      growth in a mouse model that mimics advanced stages of the disease, and reduced
      the expression of a number of biomarkers linked to PrC progression including
      pAKT, prostate specific antigen, histone deacetylases, and androgen receptor. In
      summary, this is the first article to report that Zyflamend, when provided at
      human equivalent doses, can potentiate the effects of hormone deprivation on
      tumor regression and growth inhibition of androgen-dependent and castrate
      resistant PrC tumors in vivo.

PMID- 22663544
TI  - Acute vision loss associated with retinal circulatory disturbances after
      intravitreal injection of bevacizumab.
AB  - PURPOSE: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth
      factor (VEGF), specifically binds to VEGF protein, and inhibits angiogenesis.
      Intravitreal/intracameral injection of bevacizumab has been reported as another
      treatment option for patients with various ocular ischemic conditions. However,
      we report 4 cases of acute vision loss after bevacizumab intravitreal injection.
      METHODS: Intravitreal bevacizumab injections were administrated to 2 ocular
      ischemic syndrome (OIS) patients and 2 central retinal vein occlusion (CRVO)
      patients. Best-corrected visual acuity (BCVA), intraocular pressure (IOP),
      funduscopic findings, and fluorescein angiography were evaluated before and after
      the treatments. RESULTS: All 4 cases presented with acute vision loss within 1
      week after bevacizumab injection, before its clearance from the eye, and showed
      that microcirculatory disturbances occurred in the retina. CONCLUSIONS: We
      believe that intravitreal injection of bevacizumab should be undertaken with
      extreme caution in patients with a history of cerebral infarction, especially
      with OIS or nonischemic CRVO, and with diabetic retinopathy and vitrectomized eye
      with pseudophakia.

PMID- 22663545
TI  - Palladium catalyzed C-H functionalization of O-arylcarbamates: selective ortho
      bromination using NBS.
AB  - A series of cyclometalated palladium complexes derived from O-phenylcarbamates
      has been synthesized by the reaction of the respective carbamates with Pd(OAc)(2)
      in the presence of acids, CF(3)CO(2)H, CF(3)SO(3)H, and p-TsOH. The palladacycles
      were observed to coordinate amines and electron rich anilines but not
      sulfonamides or carboxamides. Analysis of the (t)Bu-NH(2) adduct of the
      palladacycle 2b (2b.(t)Bu-NH(2)) by NMR spectroscopy (NOE) revealed a cis
      coordination of the amine. However, the amine adducts failed to undergo ortho
      amination (C-N bond formation) under varied reaction conditions. Notably, the
      palladacycle 1d was found to react efficiently with N-iodosuccinimide (NIS) to
      yield the ortho-iodinated carbamate, 1e. More significantly, this reaction can be
      extended to a palladium-catalyzed ortho C-H bromination of aryl-O-carbamates even
      at 5 mol % loading of Pd(OAc)(2) using N-bromosuccinimide (NBS).

PMID- 22663546
TI  - 6-(methylamino)hexane-1,2,3,4,5-pentanol 4-(((1S,2S)-1-hydroxy-2,3-dihydro-1H,1'H
      [2,2-biinden]-2-yl)methyl)benzoate (PH46A): a novel small molecule with efficacy
      in murine models of colitis.
AB  - The indane skeleton is found naturally and in several therapeutic molecules in
      medicinal chemistry. During our work on the anti-inflammatory activity of
      naturally occurring and synthetic indanes, we have synthesized a novel indane
      scaffold that has been optimized for both anti-inflammatory activity and
      bioavailability. We have evaluated our lead molecule, PH46A, in in vivo models of
      inflammatory bowel disease (IBD), an area of considerable unmet clinical need;
      current therapies are often unable to control the course of the disease. The
      compound significantly reduced histological damage and serum amyloid A (SAA)
      levels in IL-10(-/-) colitis mice, was efficacious in the 5% dextran sulfate
      sodium (DSS) colitis model, and compared favorably with prednisolone in this
      model and supports its potential use to treat acute exacerbations of the disease.
      Further, the graded response to the compound may also lend itself to be used at a
      lower dose to maintain periods of remission.

PMID- 22663547
TI  - Triiodothyronine acutely stimulates glucose transport into L6 muscle cells
      without increasing surface GLUT4, GLUT1, or GLUT3.
AB  - BACKGROUND: Thyroid hormones (THs) act genomically to stimulate glucose transport
      by elevating glucose transporter (Slc2a) expression and glucose utilization by
      cells. However, nongenomic effects of THs are now emerging. Here, we assess how
      triiodothyronine (T(3)) acutely affects glucose transport and the content of
      GLUT4, GLUT1, and GLUT3 at the surface of muscle cells, and possible interactions
      between T(3) and insulin action. METHODS: Differentiated L6 myotubes transfected
      with myc-tagged Slc2a4 (L6-GLUT4myc) or Slc2a1 (L6-GLUT1myc) and wild-type L6
      myotubes were studied in the following conditions: control, hypothyroid (Tx), Tx
      plus T(3), Tx plus insulin, and Tx plus insulin and T(3). RESULTS: Glucose uptake
      and GLUT4 content at the cell surface decreased in the Tx group relative to
      controls. T(3) treatment for 30 minutes increased glucose transport into L6
      GLUT4myc cells without altering surface GLUT4 content, which increased only
      thereafter. The total amount of GLUT4 protein remained unchanged among the groups
      studied. The surface GLUT1 content of L6-GLUT1myc cells also remained unaltered
      after T(3) treatment; however, in these cells glucose transport was not
      stimulated by T(3). In wild-type L6 cells, although T(3) treatment increased the
      total amount of GLUT3, it did not change the surface GLUT3 content. Moreover,
      within 30 minutes, T(3) stimulation of glucose uptake was additive to that of
      insulin in L6-GLUT4myc cells. As expected, insulin elevated surface GLUT4 content
      and glucose uptake. However, interestingly, surface GLUT4 content remained
      unchanged or even dropped with T(3) plus insulin. CONCLUSIONS: These data reveal
      that T(3) rapidly increases glucose uptake in L6-GLUT4myc cells, which, at least
      for 30 minutes, did not depend on an increment in GLUT4 at the cell surface yet
      potentiates insulin action. We propose that this rapid T(3) effect involves
      activation of GLUT4 transporters at the cell surface, but cannot discount the
      involvement of an unknown GLUT.

PMID- 22663549
TI  - Stimulated thyroglobulin and neck ultrasonography facilitates postsurgical
      radioactive iodine remnant ablation selection in patients with low-risk well
      differentiated thyroid carcinoma.

PMID- 22663548
TI  - Genetic profiling in Graves' disease: further evidence for lack of a distinct
      genetic contribution to Graves' ophthalmopathy.
AB  - BACKGROUND: Graves' disease (GD), including Graves' ophthalmopathy or orbitopathy
      (GO), is an autoimmune disease with an environmental and genetic component to its
      etiology. The genetic contribution to the GO clinical phenotype remains unclear.
      Previous data from our laboratory and others have suggested that GO has no
      specific genetic component distinct from GD itself, while other reports have
      occasionally appeared suggesting that polymorphisms in genes such as CTLA4 and
      IL23R specifically increase the risk for GO. One of the criticisms of all these
      reports has been the clinical definition of the GO phenotype as distinct from
      hyperthyroid GD devoid of clinically significant eye involvement. The objective
      of this study was to take advantage of a phenotypically pure group of GD patients
      with GO and examine a series of genes associated with GD to determine if any were
      more definitively associated with GO rather than Graves' thyroid disease itself.
      METHODS: To further examine whether specific susceptibility genes are associated
      with GO, we have performed further genetic association studies using highly
      characterized GO patients, many of whom had undergone orbital decompression
      surgery for their exophthalmos. We genotyped HLA, CTLA4, IL23R, and TSHR genes in
      a group of 256 Caucasian patients with severe GO (n=199) and less severe GO
      (n=57), and 90 patients with GD but no clinically apparent GO. RESULTS: We found
      that the allele and genotype frequencies were not statistically different between
      GO and non-GO patients for any of the genes and gene combinations assessed.
      CONCLUSIONS: These results provide further evidence that patients with GO do not
      have a distinct genetic susceptibility to their eye disease and again suggest
      that environmental and/or epigenetic influences are at play.

PMID- 22663550
TI  - Undetectable serum thyroglobulin levels in patients with medullary thyroid
      carcinoma after total thyroidectomy without radioiodine ablation.
AB  - BACKGROUND: Recently, we reported that the thyroglobulin (Tg) doubling time (DT)
      was the most potent prognostic factor in patients with papillary thyroid
      carcinoma (PTC) who underwent total thyroidectomy. Interestingly 16.2% of the
      study patients had a decrease in Tg levels over time, giving negative values in
      Tg-DT. These patients had an excellent outcome. However, most of the patients did
      not receive ablation with radioactive iodine. Therefore, whether the Tg in these
      patients was derived from persistent disease or residual thyroid tissue could not
      be concluded. To resolve this question, we measured serum Tg levels in patients
      with medullary thyroid carcinoma (MTC) who underwent total thyroidectomy using
      similar surgical techniques for the treatment of PTC. METHODS: Twenty-seven
      consecutive patients with MTC who underwent total thyroidectomy were selected. Of
      them, five patients with antibodies to Tg were excluded from the study. In the
      remaining 22 patients, serum Tg levels were measured before and after surgery.
      None of the patients received radioactive iodine ablation. They were prescribed
      levothyroxine as a replacement for the lost thyroid function. RESULTS: Serum Tg
      levels were detectable preoperatively, while postoperative serum Tg levels were
      lower than the detectable level, 0.5 ng/mL, in all 22 patients. CONCLUSIONS: The
      results indicate that most of the patients with detectable Tg levels and negative
      Tg-DT values after total thyroidectomy for PTC in our previous study had
      persistent disease, and that their serum Tg was not from residual thyroid tissue,
      suggesting that up to 50% of patients with persistent PTC have a decrease in
      serum Tg levels in response to thyroid-stimulating hormone-suppressive therapy.

PMID- 22663552
TI  - Superhydrophobic colloidally textured polythiophene film as superior
      anticorrosion coating.
AB  - In this paper, we demonstrated for the first time the use of electrodeposited
      superhydrophobic conducting polythiophene coating to effectively protect the
      underlying steel substrate from corrosion attack: by first preventing water from
      being absorbed onto the coating, thus preventing the corrosive chemicals and
      corrosion products from diffusing through the coating, and second by causing an
      anodic shift in the corrosion potential as it galvanically couples to the metal
      substrate. Standard electrochemical measurements revealed the steel coated with
      antiwetting nanostructured polythiophene film, which was immersed in chloride
      solution of different pH and temperature for up to 7 days, is very well protected
      from corrosion evidenced by protection efficiency of greater than 95%.
      Fabrication of the dual properties superhydrophobic anticorrosion nanostructured
      conducting polymer coating follows a two-step coating procedure that is very
      simple and can be used to coat any metallic surface. 

PMID- 22663551
TI  - Five-year change in morphological and functional alterations of the thyroid
      gland: the Study of Health in Pomerania.
AB  - BACKGROUND: While cross-sectional data on thyroid epidemiology are common, few
      longitudinal data on the incidence and progression of thyroid disorders exist.
      The aim of this study was to analyze the 5-year change and the incidence of
      morphological and functional alterations of the thyroid gland in a previously
      iodine-deficient area. METHODS: We used 5-year follow-up data based on 2941
      participants (20-79 years) of the population-based Study of Health in Pomerania.
      The thyroid structure and size were measured by ultrasonography. Thyroid function
      and serum autoantibodies to thyroperoxidase (anti-TPO-Ab) were evaluated.
      RESULTS: During follow-up, the median iodine/creatinine ratio decreased slightly
      from 134.2 to 130.4 MUg/g. The mean thyroid volume was nonsignificantly increased
      by 0.73 mL [confidence interval (CI) -1.68-3.41 mL]. The incidence rate of goiter
      was 34.0 [CI 30.7-37.7] per 1000 person-years (py), the incident rate of nodules
      was 16.6 [CI 14.5-19.1] per 1000 py. Median serum thyrotropin levels increased
      slightly (0.10 [CI -0.10-0.34 mIU/L]). The incidence of positive anti-TPO-Ab was
      3.4 [CI 2.6-4.7] per 1000 py. For all thyroid parameters, the regression rates
      were higher than the incidence rates. CONCLUSIONS: After iodine fortification
      became effective in this previously iodine-deficient region, there is a negative
      net balance between occurring and reverting goiter and nodules. Along with
      balanced incidences of hyper- and hypothyroid dysfunction and the low incidence
      of autoimmune-related findings, these findings indicate that the current iodine
      status is sufficient to prevent iodine deficiency-related disorders in the adult
      population of the study region.

PMID- 22663553
TI  - Translational research in oncology: the need of additional in vitro preclinical
      testing methods for new drugs.
AB  - Cancer remains one of the leading causes of death in the Western world. Despite
      bold advances in therapeutic oncology, new drug development is infamously
      ineffective due to the lack of predictive in vitro models. Most patients that
      suffer from cancer do not die from the primary tumor but due to the development
      of metastases. And yet current in vitro screening methods for new drugs in
      oncology still largely target cytotoxicity or the inhibition of cell growth, in
      which a potential anti-metastatic activity cannot be assessed. Herein the current
      in vitro models in oncology are reviewed and a new rationale for the pre-clinical
      development of specific, anti-metastatic therapeutic agents is introduced.

PMID- 22663554
TI  - Electrochemotherapy: progress and prospects.
AB  - Treatment of recurrent or unresectable cutaneous and subcutaneaous tumors
      continues to be a major therapeutic challenge. Electrochemotherapy (ECT) is a
      palliative treatment of cutaneous and subcutaneous tumor nodules for which
      standard treatments (e.g. radiotherapy, chemotherapy, and surgery) have failed or
      proved to be insufficient. ECT combines the electropulsation of tumor cells (by
      local application of electric pulses) and the administration of antineoplastic
      drugs such as cisplatin or bleomycin (either intravenous or intratumoral). The
      permeability of the cancer cells to these poorly permeant anti-tumor drugs is
      transiently increased up to a hundred-fold. ECT is thus an efficient loco
      regional therapy for palliative treatment of unresectable recurrent tumor nodules
      with overall objective response rates of approximatively 80-90% and has
      satisfactory cosmetic results. The next challenge for ECT is the treatment of
      deep-seated tumors and metastases. The joint therapy of ECT and electrotransfer
      of immune-stimulating genes or electro-photodynamic therapy could be a promising
      strategy for cancer eradication.

PMID- 22663555
TI  - Analysis of trajectories for targeting of magnetic nanoparticles in blood
      vessels.
AB  - The technique of magnetic drug targeting deals with binding drugs or genetic
      material to superparamagnetic nanoparticles and accumulating these complexes via
      an external magnetic field in a target region. For a successful approach, it is
      necessary to know the required magnetic setup as well as the physical properties
      of the complexes. With the help of computational methods, the complex
      accumulation and behavior can be predicted. We present a model for vascular
      targeting with a full three-dimensional analysis of the magnetic and fluidic
      forces and a subsequent evaluation of the resulting trajectories of the
      complexes. These trajectories were calculated with respect to the physiological
      boundary conditions, the magnetic properties of both the external field and the
      particles as well as the hydrodynamics of the fluid. We paid special regard to
      modeling input parameters like flow velocity as well as the distribution
      functions of the hydrodynamic size and magnetic moment of the nanoparticle
      complexes. We are able to estimate the amount of complexes, as well as the
      spatial distribution of those complexes. Additionally, we examine the development
      of the trapping rate for multiple passages of the complexes and compare the
      influence of several input parameters. Finally, we provide experimental data of
      an ex vivo flow-loop system which serves as a model for large vessel targeting.
      In this model, we achieve a deposition of lentivirus/magnetic nanoparticle
      complexes in a murine aorta and compare our simulation with the experimental
      results gained by a non-heme-iron assay. 

PMID- 22663556
TI  - Identification with the retail organization and customer-perceived employee
      similarity: effects on customer spending.
AB  - Two constructs important to academicians and managers are the degree to which
      employees and customers identify with an organization, employee organizational
      identification (employee OI) and customer-company identification (customer
      identification), respectively. This research examines the effects of these
      identification constructs and the related construct of customer perceived
      similarity to employees on customer spending. Via a 1-year multilevel study of
      12,047 customers and 1,464 store employees (sales associates) covering 212 stores
      of a specialty apparel retailer, our study contributes to the literature in 2
      critical ways. First, we expand the theoretical network of employee OI and
      customer identification by examining the related construct of a customer's
      perceived similarity to store employees. We examine the incremental (not fully
      mediated) main and interaction effects of customer-perceived similarity to
      employees and employee OI on customer spending. Second, we examine the effect of
      customer identification on customer spending relative to the effect of customer
      satisfaction on customer spending. Thus, our study also contributes by
      demonstrating a potential complementary route to achieve customer spending
      (customer identification), a route that may be more readily affected by
      management than the efforts required for a sustained increase in customer
      satisfaction. Implications for academics and managers are offered.

PMID- 22663557
TI  - When and how is job embeddedness predictive of turnover? a meta-analytic
      investigation.
AB  - The present meta-analytic study introduces an overall model of the relationships
      between job embeddedness and turnover outcomes. Drawing on 65 independent samples
      (N = 42,907), we found that on-the-job and off-the-job embeddedness negatively
      related to turnover intentions and actual turnover, after controlling for job
      satisfaction, affective commitment, and job alternatives. In addition, the
      negative relationships between on-the-job embeddedness (off-the-job embeddedness)
      and turnover criteria were stronger in female-dominated samples and public
      organizations (collectivistic countries). Finally, turnover intentions, job
      search behavior, and job performance fully (partially) mediated the effect of on
      the-job embeddedness (off-the-job embeddedness) on actual turnover. The research
      and practical implications of our findings are noted, in light of study
      limitations and future research needs.

PMID- 22663558
TI  - Retraction. ''Non-viral reprogramming of skeletalmyoblasts with valproic acid for
      pluripotency''.

PMID- 22663559
TI  - New records of acanthocephalans from birds in the Philippines with a description
      of a new Porrorchis species and identification keys for the genus.
AB  - Three acanthocephalan species, Sphaerirostris turdi from the island thrush
      (Turdus poliocephalus), and Porrorchis centropusi and Porrorchis kinsellai n.
      sp., both from Philippine scops owls (Otus megalotis), are reported from Aurora
      Province, Luzon Island, Philippines. Porrorchis kinsellai n. sp. can be readily
      differentiated from previously known members of the genus by an almost perfectly
      spherical proboscis and presence of a characteristic finger-like process at the
      female posterior end, among other features. Porrorchis centropusi and Porrorchis
      hylae are regarded as synonyms by some authors, but based on several
      morphological features, they are considered separate species here. A key to the
      identification of all known species of Porrorchis (other than insufficiently
      described Porrorchis brevicanthus) is provided.

PMID- 22663560
TI  - Reading through a noisy channel: why there's nothing special about the perception
      of orthography.
AB  - The goal of research on how letter identity and order are perceived during
      reading is often characterized as one of "cracking the orthographic code." Here,
      we suggest that there is no orthographic code to crack: Words are perceived and
      represented as sequences of letters, just as in a dictionary. Indeed, words are
      perceived and represented in exactly the same way as other visual objects. The
      phenomena that have been taken as evidence for specialized orthographic
      representations can be explained by assuming that perception involves recovering
      information that has passed through a noisy channel: the early stages of visual
      perception. The noisy channel introduces uncertainty into letter identity, letter
      order, and even whether letters are present or absent. We develop a computational
      model based on this simple principle and show that it can accurately simulate
      lexical decision data from the lexicon projects in English, French, and Dutch,
      along with masked priming data that have been taken as evidence for specialized
      orthographic representations.

PMID- 22663561
TI  - Prevalence and diversity of carbapenem-resistant bacteria in untreated drinking
      water in Portugal.
AB  - We examined the prevalence and diversity of carbapenem-resistant bacteria (CRB)
      in untreated drinking water. Prevalence was estimated in plate count agar (PCA)
      and R2A media with or without antibiotics. Clonal relatedness of isolates was
      established by repetitive extragenic palindroitic (REP)-PCR. Phylogeny was based
      on the 16S rRNA gene. Antimicrobial susceptibility was assessed by disc diffusion
      methods. Genes encoding beta-lactamases and integrases were inspected by PCR. CRB
      ranged from 0.02% to 15.9% of cultivable bacteria, while ampicillin-resistant
      bacteria ranged from 1.5% to 31.4%. Carbapenem-resistant isolates affiliated with
      genera Stenotrophomonas, Pseudomonas, Janthinobacterium, Chryseobacterium,
      Sphingobacterium, Acidovorax, Caulobacter, Cupriavidus, and Sphingomonas. CRB
      were highly resistant to beta-lactams, but mostly susceptible to other classes.
      Transmissible beta-lactamase genes and integrase genes were not detected. The
      genus-specific bla(L1) was detected in 61% of the Stenotrophomonas isolates.
      Contrarily to what has been reported for extensively used antibiotics, low levels
      of carbapenem resistance were detected in untreated drinking water, often
      represented by intrinsically resistant genera. Production of chromosomal-encoded
      carbapenemases was the prevalent carbapenem resistance mechanism. Results suggest
      that the dissemination of anthropogenic-derived carbapenem resistance is at an
      early stage. This presents an opportunity to rationally develop monitoring
      strategies to identify dissemination routes and assess the impact of human
      actions in the environmental resistome.

PMID- 22663562
TI  - Tris(2,3-dibromopropyl) isocyanurate, hexabromocyclododecanes, and polybrominated
      diphenyl ethers in mollusks from Chinese Bohai Sea.
AB  - A novel brominated flame retardant (BFR), tris(2,3-dibromopropyl) isocyanurate
      (TBC), as well as hexabromocyclododecanes (HBCDs) and polybrominated diphenyl
      ethers (PBDEs), were analyzed in 11 species of mollusks collected from nine
      coastal cities around the Chinese Bohai Sea in 2009 and 2010. The detection
      frequencies were 100%, 99%, and 77% for PBDEs, HBCDs, and TBC, respectively.
      Concentrations of ?HBCDs ranged from below detection limit (nd) to 28.8 ng g(-1)
      on a dry weight (dw) basis, followed by ?(12)PBDE (0.01-20.4 ng g(-1) dw) and TBC
      (nd-12.1 ng g(-1) dw). Statistically significant linear correlations were found
      among the three BFRs. Positive correlations were found between BFRs
      concentrations and lipid content in mollusks. The concentrations tend to decrease
      with increasing trophic levels of the mollusks, implying trophic dilution rather
      than biomagnifications of the BFRs in the aquatic food chains of the sampling
      area. Among the 11 mollusks species,  Mytilus edulis  showed higher
      bioaccumulation capability than others and was therefore considered to be an
      appropriate bioindicator of contamination by the BFRs in the Chinese Bohai Sea,
      in agreement with its previous selection for the biomonitoring of organochlorine
      pesticides (OCPs) and polychlorinated biphenyls (PCBs). A dramatic decrease in
      PBDE concentrations in mollusks of the area was found for the time period from
      2003 to 2010, with a half-life of only 2.3 +/- 1.7 years, reflecting a rapid
      response of mollusks to the change in pollution of the marine environment.

PMID- 22663563
TI  - Terahertz and infrared spectroscopy of gated large-area graphene.
AB  - We have fabricated a centimeter-size single-layer graphene device with a gate
      electrode, which can modulate the transmission of terahertz and infrared waves.
      Using time-domain terahertz spectroscopy and Fourier-transform infrared
      spectroscopy in a wide frequency range (10-10 000 cm(-1)), we measured the
      dynamic conductivity change induced by electrical gating and thermal annealing.
      Both methods were able to effectively tune the Fermi energy, E(F), which in turn
      modified the Drude-like intraband absorption in the terahertz as well as the
      "2E(F) onset" for interband absorption in the mid-infrared. These results not
      only provide fundamental insight into the electromagnetic response of Dirac
      fermions in graphene but also demonstrate the key functionalities of large-area
      graphene devices that are desired for components in terahertz and infrared
      optoelectronics.

PMID- 22663565
TI  - As in any rielct, the issue is always separating the wheat from the chaff.

PMID- 22663566
TI  - Stay ahead of the curve.

PMID- 22663564
TI  - Proteomic analysis of bronchoalveolar lavage fluid proteins from mice infected
      with Francisella tularensis ssp. novicida.
AB  - Francisella tularensis causes the zoonosis tularemia in humans and is one of the
      most virulent bacterial pathogens. We utilized a global proteomic approach to
      characterize protein changes in bronchoalveolar lavage fluid from mice exposed to
      one of three organisms, F. tularensis ssp. novicida, an avirulent mutant of F.
      tularensis ssp. novicida (F.t. novicida-DeltamglA), and Pseudomonas aeruginosa.
      The composition of bronchoalveolar lavage fluid (BALF) proteins was altered
      following infection, including proteins involved in neutrophil activation,
      oxidative stress, and inflammatory responses. Components of the innate immune
      response were induced including the acute phase response and the complement
      system; however, the timing of their induction varied. F. tularensis ssp.
      novicida infected mice do not appear to have an effective innate immune response
      in the first hours of infection; however, within 24 h, they show an upregulation
      of innate immune response proteins. This delayed response is in contrast to P.
      aeruginosa infected animals which show an early innate immune response. Likewise,
      F.t. novicida-DeltamglA infection initiates an early innate immune response;
      however, this response is diminished by 24 h. Finally, this study identifies
      several candidate biomarkers, including Chitinase 3-like-1 (CHI3L1 or YKL-40) and
      peroxiredoxin 1, that are associated with F. tularensis ssp. novicida but not P.
      aeruginosa infection.

PMID- 22663567
TI  - Burned by the burning season.

PMID- 22663568
TI  - International.

PMID- 22663569
TI  - Federal.

PMID- 22663570
TI  - States.

PMID- 22663571
TI  - Science.

PMID- 22663573
TI  - Business.

PMID- 22663572
TI  - Technology.

PMID- 22663574
TI  - Control strategies sought for nitrogen deposition.

PMID- 22663576
TI  - The International Congress of Toxicology-VII.

PMID- 22663575
TI  - The fate of the oil spilled from the exxon valdez.

PMID- 22663577
TI  - Plan now to join colleagues.

PMID- 22663578
TI  - New solvent-free sample preparation techniques.

PMID- 22663579
TI  - ES&T Information Express.

PMID- 22663580
TI  - Solid-phase extraction of polar organic pollutants from water.

PMID- 22663581
TI  - A groundwater protection strategy for lined landfills.

PMID- 22663582
TI  - The Military's Role in Protection of the Ozone Layer.

PMID- 22663584
TI  - Industry's Future: Changing Patterns of Industrial Research.

PMID- 22663583
TI  - Rethinking traceability.

PMID- 22663585
TI  - Instruments.

PMID- 22663586
TI  - Hazardous waste.

PMID- 22663587
TI  - Air pollution.

PMID- 22663588
TI  - Water treatment.

PMID- 22663589
TI  - Publications.

PMID- 22663591
TI  - Services.

PMID- 22663590
TI  - Software.

PMID- 22663593
TI  - professional services directory.

PMID- 22663592
TI  - Classified section.

PMID- 22663595
TI  - The language of colloid and interface science.

PMID- 22663594
TI  - Acs publications.

PMID- 22663597
TI  - Rheological investigation and its correlation with permeability coefficient of
      drug loaded carbopol gel: influence of absorption enhancers.
AB  - CONTEXT: The present study was planned to investigate the effect of absorption
      enhancers on the microstructure of Losartan potassium gel and hence its influence
      on the diffusion of Losartan potassium across nasal mucosa. METHOD: Losartan
      potassium loaded carbopol gel (1% w/v) with and without absorption enhancers was
      prepared. Polyethylene glycol (PEG) 4000 and ethanol were used as absorption
      enhancers. Microstructural elucidation of prepared gels was done using shear
      rheology. Ex vivo drug release studies were performed on the prepared gels.
      RESULTS: It was observed that the absorption enhancers PEG 4000 and ethanol
      altered the gel microstructure. The prepared gels were viscoelastic in nature
      suggesting their suitability for topical application. Permeability coefficient of
      Losartan potassium loaded into gels was found to be inversely proportional to the
      storage modulus. Thus increase in storage modulus lead to slow drug diffusion.
      CONCLUSION: The current study emphasizes on the fact that selection of polymeric
      carrier for nasal drug delivery and/or absorption enhancer strongly influence the
      microstructure of the gel and hence the pharmaceutical performance of the
      formulation.

PMID- 22663598
TI  - Electronic structures of ruthenium and osmium complexes of 9,10
      phenanthrenequinone.
AB  - The reaction of 9,10-phenanthrenequinone (PQ) with [M(II)(H)(CO)(X)(PPh(3))(3)]
      in boiling toluene leads to the homolytic cleavage of the M(II)-H bond, affording
      the paramagnetic trans-[M(PQ)(PPh(3))(2)(CO)X] (M = Ru, X = Cl, 1; M = Os, X =
      Br, 3) and cis-[M(PQ)(PPh(3))(2)(CO)X] (M = Ru, X = Cl, 2; M = Os, X = Br, 4)
      complexes. Single-crystal X-ray structure determinations of 1, 2.toluene, and
      4.CH(2)Cl(2), EPR spectra, and density functional theory (DFT) calculations have
      substantiated that 1-4 are 9,10-phenanthrenesemiquinone radical (PQ(*-))
      complexes of ruthenium(II) and osmium(II) and are defined as trans-[Ru(II)(PQ(*
      ))(PPh(3))(2)(CO)Cl] (1), cis-[Ru(II)(PQ(*-))(PPh(3))(2)(CO)Cl] (2), trans
      [Os(II)(PQ(*-))(PPh(3))(2)(CO) Br] (3), and cis-[Os(II)(PQ(*-))(PPh(3))(2)(CO)Br]
      (4). Two comparatively longer C-O [average lengths: 1, 1.291(3) A; 2.toluene,
      1.281(5) A; 4.CH(2)Cl(2), 1.300(8) A] and shorter C-C lengths [1, 1.418(5) A;
      2.toluene, 1.439(6) A; 4.CH(2)Cl(2), 1.434(9) A] of the OO chelates are
      consistent with the presence of a reduced PQ(*-) ligand in 1-4. A minor
      contribution of the alternate resonance form, trans- or cis
      [M(I)(PQ)(PPh(3))(2)(CO)X], of 1-4 has been predicted by the anisotropic X- and Q
      band electron paramagnetic resonance spectra of the frozen glasses of the
      complexes at 25 K and unrestricted DFT calculations on 1, trans
      [Ru(PQ)(PMe(3))(2)(CO)Cl] (5), cis-[Ru(PQ)(PMe(3))(2)(CO)Cl] (6), and cis
      [Os(PQ)(PMe(3))(2)(CO)Br] (7). However, no thermodynamic equilibria between
      [M(II)(PQ(*-))(PPh(3))(2)(CO)X] and [M(I)(PQ)(PPh(3))(2)(CO)X] tautomers have
      been detected. 1-4 undergo one-electron oxidation at -0.06, -0.05, 0.03, and 
      0.03 V versus a ferrocenium/ferrocene, Fc(+)/Fc, couple because of the formation
      of PQ complexes as trans-[Ru(II)(PQ)(PPh(3))(2)(CO)Cl](+) (1(+)), cis
      [Ru(II)(PQ)(PPh(3))(2)(CO)Cl](+) (2(+)), trans-[Os(II)(PQ)(PPh(3))(2)(CO)Br](+)
      (3(+)), and cis-[Os(II)(PQ)(PPh(3))(2)(CO)Br](+) (4(+)). The trans isomers 1 and
      3 also undergo one-electron reduction at -1.11 and -0.96 V, forming PQ(2-)
      complexes trans-[Ru(II)(PQ(2-))(PPh(3))(2)(CO)Cl](-) (1(-)) and trans
      [Os(II)(PQ(2-))(PPh(3))(2)(CO)Br](-) (3(-)). Oxidation of 1 by I(2) affords
      diamagnetic 1(+)I(3)(-) in low yields. Bond parameters of 1(+)I(3)(-) [C-O,
      1.256(3) and 1.258(3) A; C-C, 1.482(3) A] are consistent with ligand oxidation,
      yielding a coordinated PQ ligand. Origins of UV-vis/near-IR absorption features
      of 1-4 and the electrogenerated species have been investigated by
      spectroelectrochemical measurements and time-dependent DFT calculations on 5, 6,
      5(+), and 5(-).

PMID- 22663599
TI  - Color vision: "OH-site" rule for seeing red and green.
AB  - Eyes gather information, and color forms an extremely important component of the
      information, more so in the case of animals to forage and navigate within their
      immediate environment. By using the ONIOM (QM/MM) (ONIOM = our own N-layer
      integrated molecular orbital plus molecular mechanics) method, we report a
      comprehensive theoretical analysis of the structure and molecular mechanism of
      spectral tuning of monkey red- and green-sensitive visual pigments. We show that
      interaction of retinal with three hydroxyl-bearing amino acids near the beta
      ionone ring part of the retinal in opsin, A164S, F261Y, and A269T, increases the
      electron delocalization, decreases the bond length alternation, and leads to
      variation in the wavelength of maximal absorbance of the retinal in the red- and
      green-sensitive visual pigments. On the basis of the analysis, we propose the "OH
      site" rule for seeing red and green. This rule is also shown to account for the
      spectral shifts obtained from hydroxyl-bearing amino acids near the Schiff base
      in different visual pigments: at site 292 (A292S, A292Y, and A292T) in bovine and
      at site 111 (Y111) in squid opsins. Therefore, the OH-site rule is shown to be
      site-specific and not pigment-specific and thus can be used for tracking spectral
      shifts in any visual pigment.

PMID- 22663600
TI  - Particle-particle chemistry between micrometer-sized PbSO4 and CaCO3 particles in
      turbulent flow initiated by liquid water.
AB  - A mixture of natural and anthropogenic particles is ubiquitous in the troposphere
      and exerts an important influence on air quality. This work reports the study of
      mixing and heterogeneous chemistry of particles of natural-like mineral dust
      (CaCO(3)) and anthropogenic-like microparticle (PbSO(4)) in turbulent air flow
      under varying relative humidity. Sparse monolayers of laboratory-generated
      particles were collected on substrates using impaction. The grain size
      distribution and chemistry of micrometer-sized particles were determined as
      CaCO(3)-PbSO(4) internal and external mixtures by Raman imaging, scanning
      electron microscopy, and time-of-flight static secondary ionization mass
      spectrometry. The condensation of a thin water layer on mixed aggregates
      initiates the formation of complex internal mixtures of Pb(3)(CO(3))(2)(OH)(2),
      PbCO(3), CaSO(4).2H(2)O, CaCO(3), and PbSO(4) fine particles. These heterogeneous
      chemistry processes which may occur in ambient air can increase dramatically the
      amounts of hazardous breathable particles.

PMID- 22663601
TI  - Regioisomerism in the synthesis of a chiral aminotetralin drug compound:
      unraveling mechanistic details and diastereomer-specific in-depth NMR
      investigations.
AB  - During chemical process development of a novel 2-aminotetralin derivative
      intended for use as an antidepressant, scrutiny of the byproduct present in the
      drug molecule revealed a set of regioisomers. Detailed studies showed that this
      impurity issue originated from an early synthetic step in which a brominated
      tetralone motif was generated in a ring-closing protocol. It was found that this
      reaction was accompanied by a migration of the aromatic bromo substituent via
      different bromonium species along two discrete pathways. This example of the
      halogen dance reaction resulted in the formation of a series of tetralone
      impurities with a bromine distributed across all available aromatic positions of
      the tetralin nucleus. Subsequently, when subjected to reductive amination
      conditions, each of these tetralones gave rise to pairs of aminotetralins in a
      diastereomeric relationship. NMR investigations revealed that the alicyclic
      portion of the compounds thus formed displayed very complex signal patterns,
      which required further in-depth studies using a variety of sophisticated
      techniques. As a result, a deep insight into the structural features of the
      current 2-aminotetralin family was obtained, which is emphasized by the
      definition of a novel "0.2 ppm rule" allowing the absolute configuration at
      tetralin C-2 to be determined.

PMID- 22663758
TI  - Electrical stimulation superimposed on voluntary training can limit sensory
      integration in neural adaptations.
AB  - P. Bezerra, S. Zhou, Z. Crowley, A. Davie, and R. Baglin (2011) suggested that
      the neural mechanisms responsible for steadiness improvement relate in particular
      to the discharge behavior of motor units and the practice and learning of skills
      rather than the strength gain after electromyostimulation superimposed over
      voluntary training. However, the afferent inputs are determining in control of
      the force level produced and thus contribute to ensure muscle steadiness. Hence,
      it is possible that electromyostimulation interferes in neurophysiological
      afference integration and prevents neural adaptations that enable improvement of
      the control of force (and then muscle steadiness) to occur. Therefore, the neural
      adaptations induced by electromyostimulation superimposed onto voluntary training
      should also be researched in relation to the sensory pathways.

PMID- 22663759
TI  - The effect of telephone consultation on the quality of life of patients receiving
      interferon therapy: a quasi-experimental study.
AB  - OBJECTIVE: The aim of this study was to compare the effects of telephone
      consultation and attendance education on the quality of life of patients with
      hepatitis B or C receiving interferon therapy. SUBJECTS AND METHODS: Through a
      quasi-experimental study, 80 hepatitis patients were randomly assigned to one of
      the two educational methods. Patients completed the Quality of Life Questionnaire
      once upon entering the study and also 4 and 12 weeks after the treatment. Then,
      the results were compared. One group received education during monthly visits at
      the center, and another group got counseling over the telephone for 3 months. The
      data were analyzed using SPSS software (IBM, Armonk, NY). RESULTS: The results
      showed that the overall quality of life in both groups 4 weeks and 12 weeks after
      the intervention had significant differences from the pre-intervention period;
      however, these differences were more significant in the telephone counseling
      group. CONCLUSIONS: By virtue of the fact that no significant difference was
      found between the results of traditional education and telephone consultation and
      considering the high volume of patients in centers, remote distance between
      patients and centers, and also limited staff time, telephone advice can take the
      place of traditional education methods.

PMID- 22663760
TI  - Diabetes cardiovascular complications.

PMID- 22663761
TI  - The malleability of spatial skills: a meta-analysis of training studies.
AB  - Having good spatial skills strongly predicts achievement and attainment in
      science, technology, engineering, and mathematics fields (e.g., Shea, Lubinski, &
      Benbow, 2001; Wai, Lubinski, & Benbow, 2009). Improving spatial skills is
      therefore of both theoretical and practical importance. To determine whether and
      to what extent training and experience can improve these skills, we meta-analyzed
      217 research studies investigating the magnitude, moderators, durability, and
      generalizability of training on spatial skills. After eliminating outliers, the
      average effect size (Hedges's g) for training relative to control was 0.47 (SE =
      0.04). Training effects were stable and were not affected by delays between
      training and posttesting. Training also transferred to other spatial tasks that
      were not directly trained. We analyzed the effects of several moderators,
      including the presence and type of control groups, sex, age, and type of
      training. Additionally, we included a theoretically motivated typology of spatial
      skills that emphasizes 2 dimensions: intrinsic versus extrinsic and static versus
      dynamic (Newcombe & Shipley, in press). Finally, we consider the potential
      educational and policy implications of directly training spatial skills.
      Considered together, the results suggest that spatially enriched education could
      pay substantial dividends in increasing participation in mathematics, science,
      and engineering.

PMID- 22663762
TI  - Trabecular bone response to mechanical loading in ovariectomized Sprague-Dawley
      rats depends on baseline bone quantity.
AB  - Mechanical loading is one of the determining factors for bone modulation, and is
      therefore frequently used to treat or prevent bone loss; however, there appears
      to be no data on the effects of baseline bone quantity on this response. This
      study aimed to verify whether baseline bone quantity affects osteoporotic
      trabecular bone adaptive response to mechanical stimulation. Twenty-four female
      Sprague-Dawley (SD) rats were ovariectomized (OVX). After 3 weeks of OVX, rats
      were divided into a high bone quantity and a low bone quantity group, and rats in
      each group were then subdivided into 4 groups that were exposed to different
      loading strategies. In the loading groups, tibiae were stimulated through axial
      loading at 2000MUepsilon of strain, for 1500 cycles each of 75s, 150s, or 250s.
      The sham treatment groups received no loading. Changes in BV/TV for trabecular
      bone in the tibia were measured at the baseline (before loading), and at 3 weeks
      and 6 weeks after loading. BV/TVs in loading groups of the low baseline bone
      quantity group were significantly increased at 6 weeks, compared with those in
      the no-loading groups (p<0.05), while those in the high quantity groups were not
      increased (p>0.05). A significant negative correlation was observed between
      baseline BV/TV and its relative variations at 3 weeks or 6 weeks (p<0.05). These
      results indicate that adaptive responses of osteoporotic trabecular bone to
      mechanical loading depend on baseline bone quantity.

PMID- 22663764
TI  - Study on the reversible changes of the surface properties of an L-cysteine self
      assembled monolayer on gold as a function of pH.
AB  - A stimuli-response biological surface of L-cysteine was prepared on a
      polycrystalline gold surface from aqueous solution. The effect of the pH value of
      the rinsing solution on the surface composition was studied with X-ray
      photoelectron spectroscopy (XPS). Qualitative and quantitative analysis of the
      amino, carboxyl, and thiol functional groups of these self-assembled monolayers
      indicate that L-cysteine molecules exist in the neutral and zwitterionic forms
      and that they are sensitive to the pH of the rinsing solution. In addition, the
      wetting properties of the functionalized surface were studied by contact angle
      (CA) analysis: they were also dependent on the pH of the rinsing solution.
      Furthermore, it was shown that this functionalization process was reversible.

PMID- 22663763
TI  - Histopathology associated with angiostrongylosis in Akodon species (Rodentia:
      Sigmodontinae) from Sierra de la Ventana, Buenos Aires, Argentina.
AB  - Angiostrongylus is a metastrongylid nematode genus that includes species found in
      carnivores, rodents, and occasionally primates (including humans). About 100
      species of wild sigmodontine rodents occur in Argentina, 16 of which are species
      of Akodon. The lungs of Akodon azarae and Akodon dolores from Sierra de la
      Ventana, Buenos Aires, Argentina, were examined, and 2 of 10 A. dolores specimens
      were positive for angiostrongylosis, showing macroscopic lesions of verminous
      pneumonia. Adults found were identified as Angiostrongylus morerai.
      Histopathology of the lungs revealed multiple nodules in the interstitium,
      alveoli, and vessels, resulting in interstitial fibrosis and the destruction of
      small capillaries and arterioles. Since extensive pathology in the lung was noted
      here from only 2 adults, it is probable that heavier infections may cause
      mortality in their hosts. This is the first record of this nematode species from
      A. dolores , expanding its geographic distribution to the southwest of Buenos
      Aires Province, and the first description of the histopathology of larval
      angiostrongylosis in a wild rodent from South America.

PMID- 22663765
TI  - Systemic delivery of siRNA by chimeric capsid protein: tumor targeting and RNAi
      activity in vivo.
AB  - Recently, we reported that a chimeric capsid protein assembled into a
      macromolecular container-like structure with capsid shell and the resulting
      siRNA/capsid nanocarrier complexes efficiently suppressed RFP gene expression in
      the cell culture system. To extend RNAi to the in vivo applications, we here
      demonstrated that the siRNA/capsid nanocarrier complexes could have tumor
      specific targeting ability in vivo as well as the increased stability of siRNA
      during body circulation. When systemically administered, our siRNA/capsid
      nanocarrier complexes delivered siRNA to tumor tissues and efficiently suppressed
      RFP gene expression in tumor-bearing mice. The enhanced longevity of siRNA in
      vivo could be explained by shielding effect derived from the capsid shell, where
      the encapsulated siRNAs are protected from nucleases in plasma. The multivalent
      RGD peptides on shell surface, as a result of self-assembling of capsid protein
      subunits, showed efficient delivery of siRNA to the tumor tissues in vivo, due to
      the RGD-mediated binding to integrin receptors overexpressed on tumor cells.
      Moreover, the prolonged in vivo circulation time of our siRNA/capsid nanocarrier
      complexes increased the potential to serve as siRNA carriers for optimal in vivo
      RNAi. These results provide an alternative approach to systemically deliver siRNA
      to the tumor sites as well as to enhance the stability of siRNA in vivo.
      Therefore, our results revealed the promising potential of our capsid nanocarrier
      system as a therapeutic siRNA carrier for cancer treatment.

PMID- 22663766
TI  - The chronic toxicity of molybdate to marine organisms. I. Generating reliable
      effects data.
AB  - A scientific research program was initiated by the International Molybdenum
      Association (IMOA) which addressed identified gaps in the environmental toxicity
      data for the molybdate ion (MoO(4)(2-)). These gaps were previously identified
      during the preparation of EU-REACH-dossiers for different molybdenum compounds
      (European Union regulation on Registration, Evaluation, Authorization and
      Restriction of Chemical substances; EC, 2006). Evaluation of the open literature
      identified few reliable marine ecotoxicological data that could be used for
      deriving a Predicted No-Effect Concentration (PNEC) for the marine environment.
      Rather than calculating a PNEC(marine) using the assessment factor methodology on
      a combined freshwater/marine dataset, IMOA decided to generate sufficient
      reliable marine chronic data to permit derivation of a PNEC by means of the more
      scientifically robust species sensitivity distribution (SSD) approach (also
      called the statistical extrapolation approach). Nine test species were
      chronically exposed to molybdate (added as sodium molybdate dihydrate,
      Na(2)MoO(4).2H(2)O) according to published standard testing guidelines that are
      acceptable for a broad range of regulatory purposes. The selected test organisms
      were representative for typical marine trophic levels: micro-algae/diatom
      (Phaeodactylum tricornutum, Dunaliella tertiolecta), macro-alga (Ceramium
      tenuicorne), mysids (Americamysis bahia), copepod (Acartia tonsa), fish
      (Cyprinodon variegatus), echinoderms (Dendraster exentricus, Strongylocentrotus
      purpuratus) and molluscs (Mytilus edulis, Crassostrea gigas). Available
      NOEC/EC(10) levels ranged between 4.4 mg Mo/L (blue mussel M. edulis) and 1174 mg
      Mo/L (oyster C. gigas). Using all available reliable marine chronic effects data
      that are currently available, a HC(5,50%) (median hazardous concentration
      affecting 5% of the species) of 5.74(mg Mo)/L was derived with the statistical
      extrapolation approach, a value that can be used for national and international
      regulatory purposes.

PMID- 22663767
TI  - Increased phospholipase A2 activity with phosphorylation of peroxiredoxin 6
      requires a conformational change in the protein.
AB  - We have shown previously and confirmed in this study that the phospholipase A(2)
      (PLA(2)) activity of peroxiredoxin 6 (Prdx6) is markedly increased by
      phosphorylation. This report evaluates the conformation and thermodynamic
      stability of Prdx6 protein after phosphorylation to understand the physical basis
      for increased activity. Phosphorylation resulted in decreased negative far-UV CD,
      strengthened ANS binding, and a lack of rigid tertiary structure, compatible with
      a change in conformation to that of a molten globule. The DeltaG degrees (D) was
      3.3 +/- 0.3 kcal mol(-1) for Prdx6 and 1.7 +/- 0.7 kcal mol(-1) for pPrdx6,
      suggesting that phosphorylation destabilizes the protein. Phosphorylation of
      Prdx6 changed the conformation of the N-terminal domain exposing Trp 33, as
      determined by tryptophan fluorescence and NaI fluorescence quenching. The
      kinetics of interaction of proteins with unilamellar liposomes (50:25:15:10
      DPPC:egg PC:cholesterol:PG molar ratio) were evaluated with tryptophan
      fluorescence. pPrdx6 bound to liposomes with a higher affinity (K(d) = 5.6 +/-
      1.2 MUM) than Prdx6 (K(d) = 24.9 +/- 4.5 MUM). By isothermal titration
      calorimetry, pPrdx6 bound to liposomes with a large exothermic heat loss (DeltaH
      = -31.49 +/- 0.22 kcal mol(-1)). Correlating our conformational studies with the
      published crystal structure of oxidized Prdx6 suggests that phosphorylation
      results in exposure of hydrophobic residues, thereby providing accessibility to
      the sites for liposome binding. Because binding of the enzyme to the phospholipid
      substrate interface is a requirement for PLA(2) activity, these results indicate
      that a change in the conformation of Prdx6 upon its phosphorylation is the basis
      for enhancement of PLA(2) enzymatic activity.

PMID- 22663769
TI  - Fabrication of biodegradable polymeric nanofibers with covalently attached NO
      donors.
AB  - Many common wound healing aids are created from biodegradable polymeric
      materials. Often, these materials are unable to induce complete healing in wounds
      because of their failure to prevent infection and promote cell growth. This study
      reports the development of therapeutic materials aimed at overcoming these
      limitations through the release of a naturally occurring antimicrobial agent from
      a porous, polymeric fiber scaffold. The antimicrobial character was achieved
      through the release of nitric oxide (NO) while the porous structure was
      fabricated through electrospinning polymers into nanofibers. Three variations of
      the polymer poly(lactic-co-glycolic-co-hydroxymethyl propionic acid) (PLGH)
      modified to include thiol and NO groups were investigated. Fibers of the modified
      polymers exhibited smooth, bead free morphologies with diameters averaging
      between 200 and 410 nm. These fibers were deposited in a random manner to create
      a highly porous fibrous scaffold. The fibers were found to release NO under
      physiological pH and temperature and have the capacity to release 0.026 to 0.280
      mmol NO g(-1). The materials maintained their fibrous morphological structure
      after this exposure to aqueous conditions. The sustained morphological stability
      of the fiber structure coupled to their extended NO release gives these materials
      great potential for use in wound healing materials. 

PMID- 22663770
TI  - Female meiosis and beyond: more questions than answers?

PMID- 22663771
TI  - Degenerate molecular shuttles with flexible and rigid spacers.
AB  - The preparation and dynamic behavior of degenerate rotaxane molecular shuttles
      are described in which a benzylic amide macrocycle moves back and forth between
      two naphthalimide-glycine units along a diphenylethyne spacer or an aliphatic
      spacer consisting of a C(9), C(12), or C(26) alkyl chain. Subtle differences in
      the (1)H NMR spectra of the rotaxanes can be related to the presence of
      conformers in which the macrocycle interacts simultaneously with both glycines,
      especially in the case of the C(9) spacer. The kinetic data of the shuttling
      behavior in the C(26) rotaxane were obtained from dynamic NMR spectroscopy. The
      Eyring activation parameters were found to be DeltaH(?) = 10 +/- 1 kcal mol(-1),
      DeltaS(?) = -6.5 +/- 2.0 cal mol(-1) K(-1), DeltaG(?)(298) = 11.9 +/- 0.2 kcal
      mol(-1). For the systems with the shorter spacers, the shuttling rates were
      higher. Also in the diphenylethyne, rotaxane shuttling is rapid on the NMR time
      scale, indicating that the rigid unit does not impose a large barrier to the
      translocation of the macrocycle.

PMID- 22663772
TI  - Robot-assisted intermanual transfer of handwriting skills.
AB  - We examined whether intermanual transfer of fine motor skills can be facilitated
      by training in a virtual environment. We focused on three types of assistance:
      visual - subjects could see a reference template on a computer screen - and two
      variants of haptic assistance. Subjects held a planar robot manipulandum and were
      required to write isolated cursive letters of an approximate size of 5 cm.
      Therefore, the task was similar to writing on a horizontal blackboard. The robot
      generated forces that were directed either towards the reference template (path
      guidance) or towards the reference trajectory (trajectory guidance). The training
      protocol consisted of three assisted exercise sessions on three consecutive days.
      Performance on the following day was tested to assess retention. After training,
      the improvement in trajectory shape was only significant in trajectory guidance
      and, to a lesser extent, visual guidance. Path guidance exhibited no significant
      improvement. These effects were substantially retained one day after the end of
      training. Similar effects were observed in shape variability. Furthermore, all
      training modalities caused a reduction in movement duration, but no significant
      differences were observed among groups. These results suggest that robot
      assistance may be beneficial for improving intermanual transfer, but inclusion of
      temporal information in the guidance strategy is essential for learning to take
      place.

PMID- 22663768
TI  - Anergy in CD4 memory T lymphocytes. II. Abrogation of TCR-induced formation of
      membrane signaling complexes.
AB  - Memory and naive CD4 T cells have unique regulatory pathways for self/non-self
      discrimination. A memory cell specific regulatory pathway was revealed using
      superantigens to trigger the TCR. Upon stimulation by bacterial superantigens,
      like staphylococcal enterotoxin B (SEB), TCR proximal signaling is impaired
      leading to clonal tolerance (anergy). In the present report, we show that memory
      cell anergy results from the sequestration of the protein tyrosine kinase ZAP-70
      away from the TCR/CD3zeta chain. During SEB-induced signaling, ZAP-70 is excluded
      from both detergent-resistant membrane microdomains and the immunological
      synapse, thus blocking downstream signaling. We also show that the mechanism
      underlying memory cell anergy must involve Fyn kinase, given that the suppression
      of Fyn activity restores the movement of ZAP-70 to the immunological synapse, TCR
      proximal signaling, and cell proliferation. Thus, toleragens, including microbial
      toxins, may modulate memory responses by targeting the organizational structure
      of memory cell signaling complexes.

PMID- 22663773
TI  - Motor-reduced visual perceptual abilities and visual-motor integration abilities
      of Chinese learning children.
AB  - This study investigated the relationship between motor-reduced visual perceptual
      abilities and visual-motor integration abilities of Chinese learning children by
      employing the Developmental Test of Visual Perception (Hammill, Pearson, &
      Voress, 1993), in which both abilities are measured in a single test. A total of
      72 native Chinese learners of age 5 participated in this study. The findings
      indicated that the Chinese learners scored much higher in the visual-motor
      integration tasks than in motor-reduced visual perceptual tasks. The results
      support the theory of autonomous systems of motor-reduced visual perception and
      visual-motor integration and query current beliefs about the prior development of
      the former to the latter for the Chinese learners. To account for the Chinese
      participants' superior performance in visual-motor integration tasks over motor
      reduced visual perceptual tasks, the visual-spatial properties of Chinese
      characters, general handwriting theories, the motor control theory and the
      psychogeometric theory of Chinese character-writing are referred to. The
      significance of the findings is then discussed.

PMID- 22663774
TI  - Analysis of the activation and heterolytic dissociation of H2 by frustrated Lewis
      pairs: NH3/BX3 (X = H, F, and Cl).
AB  - We performed a computational study of H(2) activation and heterolytic
      dissociation promoted by prototype Lewis acid/base pairs NH(3)/BX(3) (X = H, F,
      and Cl) to understand the mechanism in frustrated Lewis pairs (FLPs). Although
      the NH(3)/BX(3) pairs form strong dative bonds, electronic structure theories
      make it possible to explore the potential energy surface away from the dative
      complex, in regions relevant to H(2) activation in FLPs. A weakly bound precursor
      complex, H(3)N.H(2).BX(3), was found in which the H(2) molecule interacts side-on
      with B and end-on with N. The BX(3) group is pyramidal in the case of X = H,
      similar to the geometry of BH(5), but planar in the complexes with X = F and Cl.
      The latter complexes convert to ion pairs, [NH(4)(+)][BHX(3)(-)] with enthalpy
      changes of 7.3 and -9.4 kcal/mol, respectively. The minimum energy paths between
      the FLP and the product ion pair of the chloro and fluoro complexes were
      calculated and analyzed in great detail. At the transition state (TS), the H(2)
      bond is weakened and the BX(3) moiety has undergone significant pyramidal
      distortion. As such, the FLP is prepared to accept the incipient proton and
      hydride ion on the product-side. The interaction energy of the H(2) with the
      acid/base pair and the different contributions for the precursor and TS complex
      from an energy decomposition analysis expose the dominant factors affecting the
      reactivity. We find that structural reorganization of the precursor complex plays
      a significant role in the activation and that charge-transfer interactions are
      the dominant stabilizing force in the activated complex. The electric field
      clearly has a role in polarizing H(2), but its contribution to the overall
      interaction energy is small compared to that from the overlap of the p(N),
      sigma(H-H), sigma*(H-H), and p(B) orbitals at the TS. Our detailed analysis of
      the interaction of H(2) with the FLP provides insight into the important
      components that should be taken into account when designing related systems to
      activate H(2).

PMID- 22663775
TI  - Aerodynamics and deposition effects of inhaled submicron drug aerosol in airway
      diseases.
AB  - Particle engineering is the prime focus to improve pulmonary drug targeting with
      the splendor of nanomedicines. In recent years, submicron particles have emerged
      as prettyful candidate for improved fludisation and deposition. For effective
      deposition, the particle size must be in the range of 0.5-5 MUm. Inhalers design
      for the purpose of efficient delivery of powders to lungs is again a crucial task
      for pulmonary scientists. A huge number of DPI devices exist in the market, a
      significant number are awaiting FDA approval, some are under development and a
      large number have been patented or applied for patent. Even with superior design,
      the delivery competence is still deprived, mostly due to fluidisation problems
      which cause poor aerosol generation and deposition. Because of the cohesive
      nature and poor flow characteristics, they are difficult to redisperse upon
      aerosolization with breath. These problems are illustrious in aerosol research,
      much of which is vastly pertinent to pulmonary therapeutics. A technical review
      is presented here of advances that have been utilized in production of submicron
      drug particles, their in vitro/in vivo evaluations, aerosol effects and pulmonary
      fate of inhaled submicron powders.

PMID- 22663776
TI  - The effect of a 3-month supervised exercise programme on gait parameters of
      patients with peripheral arterial disease and intermittent claudication.
AB  - BACKGROUND: The management of peripheral arterial disease with intermittent
      claudication includes angioplasty, pharmaceutical therapy, risk factor
      modification and exercise therapy. Supervised exercise programmes are used
      sporadically but may improve the distance that an individual with claudication
      can walk. The purpose of this study was to evaluate the effectiveness of a 3
      month supervised exercise programme on improving gait parameters in patients with
      intermittent claudication. METHODS: 12 participants were recruited (mean (SD) -
      age: 67.3 (6.8) years, height: 1.67 (0.09) m, mass: 79.4 (14.0) kg, ankle
      brachial pressure index: 0.73 (0.17)) from the local vascular unit and enrolled
      in a supervised exercise programme. Kinematic and kinetic data were collected at
      the following time points: pain-free walking, initial claudication pain, absolute
      claudication pain and after a patient-defined rest period. Data were collected
      before and after the 3-month supervised exercise programme. FINDINGS: No
      significant differences were found in any of the gait parameters post
      intervention including pain-free walking speed (P=0.274), peak hip extension
      (P=0.125), peak ankle plantarflexion (P=0.254), or first vertical ground reaction
      force peak (P=0.654). No significant gait differences were found across different
      levels of pain pre- or post-intervention. INTERPRETATION: The lack of improvement
      post-intervention observed suggests that the current exercise protocol was not
      tailored to elicit significant improvements in patients with intermittent
      claudication, specifically. The results indicate that exercise programmes may
      show improved results post-intervention if they are longer in duration and varied
      in intensity. Further research into more detailed muscle and biomechanical
      adaptations is needed to inform exercise programmes specific to this population.

PMID- 22663777
TI  - Effects of force levels on error compensation in periodic bimanual isometric
      force control.
AB  - The authors examined whether force level interacts with the presence or absence
      of vision in bimanual force control. Participants produced periodic isometric
      forces such that the sum of the 2 finger forces was the target force under 4
      force levels cycling between lower levels (5-40%) of maximum voluntary
      contraction with an interval of 1000 ms. Without vision, the correlation between
      the 2 finger forces was strongly positive over all force levels. However, with
      vision the correlation changed from negative to positive with force level. The
      result with vision indicated that the strategy of the bimanual force control
      changed from force error compensation to force coupling and the available
      redundancy thus decreased with an increase in force.

PMID- 22663778
TI  - Evolution of the bone gene regulatory network.
AB  - Current fossil, embryological and genetic data shed light on the evolution of the
      gene regulatory network (GRN) governing bone formation. The key proteins and
      genes involved in skeletogenesis are well accepted. We discuss when these
      essential components of the GRN evolved and propose that the Runx genes, master
      regulators of skeletogenesis, functioned in early cartilages well before they
      were co-opted to function in the making of bone. Two rounds of whole genome
      duplication, together with additional tandem gene duplications, created a genetic
      substrate for segregation of one GRN into several networks regulating the related
      tissues of cartilage, bone, enamel, and dentin. During this segregation, Runx2
      assumed its position at the top of the bone GRN, and Sox9 was excluded from bone,
      retaining its ancient role in cartilage.

PMID- 22663895
TI  - Long-term patency of complex bilobular, bisaccular, and broad-neck aneurysms in
      the rabbit microsurgical venous pouch bifurcation model.
AB  - OBJECTIVES: In experimental aneurysm models, long-term patency without
      spontaneous thrombosis is the most important precondition for analyses of
      embolization devices. We recently reported the feasibility of creating complex
      venous pouch bifurcation aneurysms in the rabbit with low morbidity, low
      mortality, and high short-term aneurysm patency. In order to further evaluate our
      model, we examined the long-term patency rate. METHODS: Various sizes of complex
      bilobular, bisaccular, and broad-neck venous pouch aneurysms were surgically
      formed at an artificially created bifurcation of both common carotid arteries in
      17 rabbits. Early aggressive anticoagulation was continued for 1 month. The
      rabbits were followed up using contrast-enhanced three-dimensional 1.5-T magnetic
      resonance angiography (CE-3D-MRA) at 1 month and up to 1 year after creation of
      the bifurcation. RESULTS: At 1-month follow-up, all but one of the created
      aneurysms and all parent vessels proved to be patent. Three animals (18%) were
      lost during follow-up for reasons unrelated to aneurysm surgery. At 1-year follow
      up, one animal showed partial and one complete spontaneous aneurysm thrombosis
      (aneurysm patency rate: 86%). Six out of 42 parent vessels were occluded at that
      time (vessel patency rate: 86%). CONCLUSIONS: Complex bilobular, bisaccular, and
      broad-neck microsurgical aneurysm formation in the rabbit bifurcation model
      demonstrates a high long-term patency rate but is complicated by high rates of
      unrelated procedural mortality and morbidity. There is no need for prolonged (>4
      weeks) anticoagulation to achieve good long-term patency in complex venous pouch
      bifurcation aneurysms.

PMID- 22663896
TI  - Stress abnormalities in individuals at risk for psychosis: a review of studies in
      subjects with familial risk or with "at risk" mental state.
AB  - Increased sensitivity to stress is known to play an important role in the
      transition to first episode psychosis (FEP). Hyperactivity of the hypothalamic
      pituitary-adrenal (HPA) axis, and, in general, an increased sensitivity to
      stress, have been hypothesised to be components of the vulnerability to
      psychosis, but whether these abnormalities are already present before the onset
      of psychosis has not yet been systematically reviewed. Here we have reviewed all
      studies examining psychological and biological markers of the stress response in
      the relatives of psychotic patients and in individuals at Ultra High Risk (UHR)
      for psychosis. In relatives, there is evidence of increased sensitivity to
      stress, as shown by increased emotional reactivity to daily life stress,
      increased adrenocorticotropic hormone (ACTH) in response to stress, increased
      pituitary volume and reduced hippocampal volume. However, evidence of increased
      cortisol levels is less consistent. On the other hand, subjects who experience
      attenuated psychotic symptoms show increased cortisol levels as well as increased
      pituitary and reduced hippocampal volumes. Moreover, this HPA axis hyperactivity
      seems to be even greater among those individuals who subsequently develop frank
      psychosis. In summary, an enhanced HPA axis response to stress appears to be part
      of the biological vulnerability to psychosis which is present prior to the onset
      of psychosis. A further increase in cortisol levels during the transition to FEP
      suggests the presence of an additive factor, possibly environmental, at this
      stage of the illness. Possible causes and consequences of HPA axis impairment in
      risk for psychosis are discussed.

PMID- 22663897
TI  - Impaired hypothalamic insulin signaling in CUMS rats: restored by icariin and
      fluoxetine through inhibiting CRF system.
AB  - Epidemiological evidence demonstrates the neuroendocrine link between stress,
      depression and diabetes. This study observed glucose intolerance of rats exposed
      to chronic unpredictable mild stress (CUMS) in oral glucose tolerance test
      (OGTT). CUMS procedure significantly up-regulated corticotropin-releasing factor
      (CRF)-related peptide urocortin 2 expression and elevated cAMP production,
      resulting in over-expression of suppressor of cytokine signaling 3 (SOCS3) in
      hypothalamic arcuate nucleus (ARC) of rats. Furthermore, SOCS3 activation blocked
      insulin signaling pathway through the suppression of insulin receptor substrate 2
      (IRS2) phosphotyrosine and phosphatidylinositol-3-kinase (PI3-K) activation in
      hypothalamic ARC of CUMS rats after high-level of insulin stimulation. These data
      indicated that CUMS procedure induced the hyperactivity of CRF system, and
      subsequently produced conditional loss of insulin signaling in hypothalamic ARC
      of rats. More importantly, icariin and fluoxetine with the ability to restrain
      CRF system hyperactivity improved insulin signaling in hypothalamic ARC of CUMS
      rats, which were consistent with the enhancement of glucose tolerance in OGTT,
      showing anti-diabetic efficacy. Although effective in OGTT, anti-diabetic drug
      pioglitazone failed to restore hypothalamic ARC CRF system hyperactivity,
      paralleling with its inability to ameliorate the loss of insulin signaling and
      depression-like behavior in CUMS rats. These observations support the hypothesis
      that signal cross-talk between hypothalamic CRF system and insulin may be
      impaired in depression with glucose intolerance and suggest that icarrin and
      fluoxetine aiming at CRF system may have great potential in the prevention and
      treatment of depression with comorbid diabetes.

PMID- 22663898
TI  - Probing interfaces between pharmaceutical crystals and polymers by neutron
      reflectometry.
AB  - Pharmaceutical powder engineering often involves forming interfaces between the
      drug and a suitable polymer. The structure at the interface plays a critical role
      in the properties and performance of the composite. However, interface structures
      have not been well understood due to a lack of suitable characterization tool. In
      this work, we have used ellipsometry and neutron reflectometry to characterize
      the structure of such interfaces in detail. Ellipsometry provided a quick
      estimate of the number of layers and their thicknesses, whereas neutron
      reflectometry provided richer structural information such as density, thickness,
      roughness, and intermixing of different layers. The combined information allowed
      us to develop an accurate model about the layered structure and provided
      information about intermixing of different layer components. Systematic use of
      these characterization techniques on several model systems suggests that the
      nature of the polymer had a small effect on the interfacial structure, while the
      solvent used in polymer coating had a large effect. These results provide useful
      information on the efforts of engineering particle properties through the control
      of the interfacial chemistry. 

PMID- 22663900
TI  - Mechanisms in psychosocial interventions for adults living with cancer:
      opportunity for integration of theory, research, and practice.
AB  - OBJECTIVE: The diagnosis and treatment of cancer are highly stressful experiences
      that can profoundly affect emotional and physical well-being. Hundreds of
      longitudinal investigations that identify risk and protective factors for
      psychological and physical adjustment in adults living with cancer and numerous
      randomized controlled psychosocial intervention trials constitute the relevant
      knowledge base on factors that promote quality of life and health in this group.
      A critical step for the development of maximally effective interventions is to
      attend to the mechanisms by which interventions achieve their effects. Our goals
      in this article are to provide a rationale for theoretical and empirical
      consideration of mediating processes in intervention research, review existing
      randomized psychosocial intervention trials for adults diagnosed with cancer that
      include evaluation of mediators, and offer recommendations for research. METHOD:
      We draw from the existing conceptual and empirical literature regarding
      examination of mediating processes and review 16 randomized controlled trials
      that include evaluations of mediators. RESULTS: The current conceptual and
      empirical literature on evaluating mediators of interventions provides robust
      rationales and procedures for testing mediators of psychosocial interventions for
      adults diagnosed with cancer. Promising classes of mediators include alterations
      in cognitions (i.e., expectancies, illness representations), self-efficacy for
      using coping strategies and other skills targeted by the intervention,
      psychological and physical symptoms related to cancer (e.g., mood disturbance,
      pain), and psychosocial resources (e.g., self-esteem). CONCLUSIONS: Focused
      attention to mechanisms underlying the efficacy of interventions can help
      integrate theory, research, and practice to promote the well-being and health of
      individuals with cancer.

PMID- 22663899
TI  - A randomized controlled trial of a behavioral economic supplement to brief
      motivational interventions for college drinking.
AB  - OBJECTIVE: Behavioral economic theory suggests that a reduction in substance use
      is most likely when there is an increase in rewarding substance-free activities.
      The goal of this randomized controlled clinical trial was to evaluate the
      incremental efficacy of a novel behavioral economic supplement (Substance-Free
      Activity Session [SFAS]) to a standard alcohol brief motivational interviewing
      (BMI) session for heavy-drinking college students. METHOD: Participants were 82
      first-year college students (50% female; 81.7% White/European American; M age =
      18.5 years, SD = 0.71) who reported 2 or more past-month heavy drinking episodes.
      After completing a baseline assessment and an individual alcohol-focused BMI,
      participants were randomized to either the SFAS or to a Relaxation Training (RT)
      control session. The SFAS was delivered in an MI style and attempted to increase
      the salience of delayed academic and career rewards and the patterns of behavior
      leading to those rewards. RESULTS: The combination of an alcohol BMI plus the
      SFAS was associated with significantly greater reductions in alcohol problems
      compared with an alcohol BMI plus RT at the 1-month and 6-month follow-up
      assessments (p = .015, etap2 = .07), an effect that was partially mediated by
      increases in protective behavioral strategies. BMI + SFAS was also associated
      with greater reductions in heavy drinking among participants who at baseline
      reported low levels of substance-free reinforcement or symptoms of depression.
      CONCLUSION: These results are consistent with behavioral economic theory and
      suggest that a single session focused on increasing engagement in alternatives to
      drinking can enhance the effects of brief alcohol interventions.

PMID- 22663901
TI  - Moving from efficacy to effectiveness in cognitive behavioral therapy for
      psychosis: a randomized clinical practice trial.
AB  - OBJECTIVE: Randomized controlled trials have attested the efficacy of cognitive
      behavioral therapy (CBT) in reducing psychotic symptoms. Now, studies are needed
      to investigate its effectiveness in routine clinical practice settings. METHOD:
      Eighty patients with schizophrenia spectrum disorders who were seeking outpatient
      treatment were randomized to a specialized cognitive behavioral intervention for
      psychosis (CBTp; n = 40) or a wait list (n = 40). The CBTp group was assessed at
      baseline, posttreatment, and 1-year follow-up. The wait list group was assessed
      at baseline, after a 4-month waiting period, at posttreatment, and after 1 year.
      The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS).
      RESULTS: The CBTp group showed significant improvement over the wait list group
      for the total PANSS score at posttreatment-postwaiting. CBTp was also superior to
      the wait list group in regard to the secondary outcomes positive symptoms,
      general psychopathology, depression, and functioning, but not in regard to
      negative symptoms. The number of dropouts during the treatment phases was low
      (11.3%). Participants perceived the treatment as helpful (98%) and considered
      themselves improved (92%). Significant pre- and posttreatment effect sizes varied
      between 0.77 for general psychopathology and 0.38 for delusional conviction. The
      positive effects of treatment could be maintained at 1-year follow-up, although
      the number of patients who had deteriorated was higher than at postassessment.
      CONCLUSIONS: Large proportions of patients in clinical practice settings benefit
      from CBTp. The efficacy of CBTp can be generalized to clinical practice despite
      the differences in patients, therapists, and deliverance.

PMID- 22663902
TI  - Patterns of therapist variability: therapist effects and the contribution of
      patient severity and risk.
AB  - OBJECTIVE: To investigate the size of therapist effects using multilevel modeling
      (MLM), to compare the outcomes of therapists identified as above and below
      average, and to consider how key variables--in particular patient severity and
      risk and therapist caseload--contribute to therapist variability and outcomes.
      METHOD: We used a large practice-based data set comprising patients referred to
      the U.K.'s National Health Service primary care counseling and psychological
      therapy services between 2000 and 2008. Patients were included if they had
      received >=2 sessions of 1-to-1 therapy (including an assessment), had a planned
      ending to treatment, and completed the Clinical Outcomes in Routine Evaluation
      Outcome Measure (CORE-OM; Barkham et al., 2001; Barkham, Mellor-Clark, Connell, &
      Cahill, 2006; Evans et al., 2002) at pre- and post-treatment. The study sample
      comprised 119 therapists and 10,786 patients, whose mean age was 42.1 years
      (71.5% were female). MLM, including Markov chain Monte Carlo procedures, was used
      to derive estimates to produce therapist effects and to analyze therapist
      variability. RESULTS: The model yielded a therapist effect of 6.6% for average
      patient severity, but it ranged from 1% to 10% as patient non-risk scores
      increased. Recovery rates for individual therapists ranged from 23.5% to 95.6%,
      and greater patient severity and greater levels of aggregated patient risk in a
      therapist's caseload were associated with poorer outcomes. CONCLUSIONS: The size
      of therapist effect was similar to those found elsewhere, but the effect was
      greater for more severe patients. Differences in patient outcomes between those
      therapists identified as above or below average were large, and greater therapist
      risk caseload, rather than non-risk caseload, was associated with poorer patient
      outcomes.

PMID- 22663904
TI  - Conformations of the apo-, substrate-bound and phosphate-bound ATP-binding domain
      of the Cu(II) ATPase CopB illustrate coupling of domain movement to the catalytic
      cycle.
AB  - Heavy metal P1B-type ATPases play a critical role in cell survival by maintaining
      appropriate intracellular metal concentrations. Archaeoglobus fulgidus CopB is a
      member of this family that transports Cu(II) from the cytoplasm to the exterior
      of the cell using ATP as energy source. CopB has a 264 amino acid ATPBD (ATP
      binding domain) that is essential for ATP binding and hydrolysis as well as
      ultimately transducing the energy to the transmembrane metal-binding site for
      metal occlusion and export. The relevant conformations of this domain during the
      different steps of the catalytic cycle are still under discussion. Through
      crystal structures of the apo- and phosphate-bound ATPBDs, with limited
      proteolysis and fluorescence studies of the apo- and substrate-bound states, we
      show that the isolated ATPBD of CopB cycles from an open conformation in the apo
      state to a closed conformation in the substrate-bound state, then returns to an
      open conformation suitable for product release. The present work is the first
      structural report of an ATPBD with its physiologically relevant product
      (phosphate) bound. The solution studies we have performed help resolve questions
      on the potential influence of crystal packing on domain conformation. These
      results explain how phosphate is co-ordinated in ATPase transporters and give an
      insight into the physiologically relevant conformation of the ATPBD at different
      steps of the catalytic cycle.

PMID- 22663903
TI  - Development and pilot evaluation of an Internet-facilitated cognitive-behavioral
      intervention for maternal depression.
AB  - OBJECTIVE: Develop and pilot an Internet-facilitated cognitive-behavioral
      treatment intervention for depression, tailored to economically disadvantaged
      mothers of young children. METHOD: Mothers (N = 70) of children enrolled in Head
      Start, who reported elevated levels of depressive symptoms, were randomized to
      either the 8-session, Internet-facilitated intervention (Mom-Net) or delayed
      intervention/facilitated treatment-as-usual (DI/TAU). Outcomes were measured
      using the Beck Depression Inventory (BDI-II; Beck, Steer, & Brown, 1996); the
      Patient Health Questionnaire 9 (PHQ-9; Spitzer et al., 1999), Behavioral
      Observations of Parent-Child Interactions using the Living in Family Environments
      coding system (LIFE; Hops, Davis, & Longoria, 1995); the Dyadic Parent-Child
      Interaction Coding Systems (DPICS; Eyberg, Nelson, Duke, & Boggs, 2005); the
      Parent Behavior Inventory (PBI; Lovejoy, Weis, O'Hare, & Rubin, 1999); and the
      Parenting Sense of Competence scale (PSOC; Gibaud-Wallston & Wandersman, 1978).
      RESULTS: Mom-Net demonstrated high levels of feasibility as indicated by low
      attrition and high program usage and satisfaction ratings. Participants in the
      Mom-Net condition demonstrated significantly greater reduction in depression, the
      primary outcome, at the level of both symptoms and estimates of criteria-based
      diagnoses over the course of the intervention. They also demonstrated
      significantly greater improvement on a questionnaire measure of parent
      satisfaction and efficacy as well as on both questionnaire and observational
      indices of harsh parenting behavior. CONCLUSIONS: Initial results suggest that
      the Mom-Net intervention is feasible and efficacious as a remotely delivered
      intervention for economically disadvantaged mothers.

PMID- 22663905
TI  - Difference of adherence, proliferation and osteogenesis of mesenchymal stem cells
      cultured on different HA/ZrO2 composites.
AB  - OBJECTIVE: To study the adherence, proliferation and osteogenesis of mesenchymal
      stem cells (MSCs) cultured on different HA/ZrO2 composites. METHODS: The simplex
      and graded HA/ZrO2 compo-sites were prepared using dry-laid method. The surface
      topography of the composites was observed by scanning electron microscope (SEM).
      The MSCs were isolated from rabbits and cultured on experimental groups (simplex
      HA/ZrO2 composite, graded HA/ZrO2 composite, pure HA or pure ZrO2 coatings
      respectively) and control group (ordinary culture plate). Then, we observed the
      adherence, proliferation and osteogenesis of the MSCs, detected the cellular
      alkaline phosphatase (ALP) activities, extracted total RNA and detected the mRNA
      expression of collagen I, osteocalcin and osteopontin using the reverse
      transcription and polymerase chain reaction (RT-PCR) method. RESULTS: The SEM
      images confirmed that the surface of the simplex HA/ZrO2 composite was coverd by
      discon-tiguous HA layer with clear visualization of the partial ZrO2 matrix,
      while the surface of the graded HA/ZrO2 composite was fairly rough with porosity.
      X-ray diffraction showed that after high temperature sintering, the ZrO2 phase
      still remained, while the HA phase was transformed to beta-Ca3(PO4)2 , alpha
      Ca3(PO4)2 and CaZrO3 phases on the surface of both composites. Cell culture
      indicated that the HA/ZrO2 composites supported cell attachment. Neither ALP
      expression nor mRNA expression of collagen I, osteocalcin or osteopontin from RT
      PCR results showed significant deviation among four groups. CONCLUSION: Among
      these four composites, the graded HA/ZrO2 composite promotes the MSCs
      proliferation and the osteogenic differentiation to a certain extent.

PMID- 22663906
TI  - Ankle fusion with a retrograde locked intramedullary nail for sequela of lower
      extremity compartment syndrome.
AB  - OBJECTIVE: To assess the value of ankle fusion with a retrograde locked
      intramedullary nail in the treatment of sequela of lower extremity compartment
      syndrome. METHODS: Thirty-five cases of equinus deformity follow-ing tibiofibular
      compartment syndrome treated by means of ankle fusion with a retrograde locked
      intramedullary nail from January 2001 to December 2010 were retrospectively
      reviewed. The complications, the time needed for bony fusion of the ankle joint
      assessed by anteroposterior and lateral X-ray photographs as well as
      patients'subjective evaluation were recorded and analysed. RESULTS: Among the 35
      patients, 15 had previously undergone surgical treatment twice on the same limb,
      13 had thrice and 7 had to be operated on four times before ankle fusion. An
      anterior midpoint approach to the ankle joint was adopted in 29 cases, while
      anterior midpoint approach plus a small incision on the posterior ankle joint was
      made in 17 cases, whereas lateral approach in 6 cases. Tarsus joint fusion was
      performed on 4 cases. The follow-up period ranged 6-124 months, averaged 40.6
      months. Bone grafting was not performed in this series. Preoperative tibial shaft
      fracture occurred in one patient and was healed after conservative treatment.
      Incision dehiscence located at previous Achilles tendon incision was found in two
      patients. As a result, one received an intramedullary nail emplacement at
      calcaneoplantar part while the wound at anterosuperior part of the other one was
      healed by dressing change. Two patients failed to bony union 5 months
      postoperatively, in which one healed 10 weeks after retrieval of proximal tibial
      nail and another by iliac grafting. Terminal necrosis of the toe due to blood
      supply dysfunction was not found in this series. All the patients were satisfied
      with the ankle joint function postoperatively. The time for bony union on X-rays
      was 9.8 weeks on average. Except for one patient who demanded removal of
      intramedullary nail, all the intramedullary nails were not retrieved at the end
      of follow-up. Nail breakage happened in one patient and no other breakage or
      backing out of the nail was found. CONCLUSIONS: Lower extremity compartment
      syndrome and residual ankle deformity often extremely impact ambulation and are
      hard to deal with because several pathologic phenomena might exist in these
      patients, for instance, poor skin conditions due to repeated preexisting surgery;
      poor perfusion in distal limbs following blood vascular injury; reflux limitation
      and long-term limb swelling due to muscle strength disturbance; osteoporosis as a
      result of long-term immobilization or limb disuse. Ankle fusion with a retrograde
      locked intramedullary nail is an optimal protocol to solve these clinical
      symptoms and rather ensures a definite fusion and firm fixation to these patients
      with simple manipulation and few complications.

PMID- 22663907
TI  - Reliability of a patient survey assessing "Short Form Injury Questionnaire 7" in
      Iran.
AB  - OBJECTIVE: Injury is a major cause of morbidity and mortality in the world. The
      assessment of patterns and severity of injury in high-risk groups is crucial for
      planning and service development. On a large scale national household survey, we
      estimated the annual incidence and the patterns of injury, the demographics of
      the injured people, as well as the service use for all injuries in Iran. The
      current study aims at assessing the reliability of the questionnaire before
      carrying out a national survey. METHODS: In a pilot study using cluster random
      sampling approach, 73 people were interviewed. The interviewers asked the
      participants to report all injuries occurred in them and the care provided during
      the previous 12 months, based on "Short Form Injury Questionnaire 7" About two
      weeks later, the interview was repeated by another interviewer. RESULTS: In our
      test-retest reliability, Kappa score was good for three and moderate for four
      questions. The question on the injured organ had the highest test-retest
      reliability with a Kappa score of 0.84. CONCLUSIONS: The reliability of the
      questionnaire and the procedure of questioning are confirmed. The ques-tionnire
      is proper for utilization in large national surveies.

PMID- 22663908
TI  - Yoga is found hazardous to the meniscus for Chinese women.
AB  - OBJECTIVE: Yoga is becoming more and more popular in the female society while the
      concomitant sports injury is seldom mentioned. Many clinicians have noted that
      yoga may result in knee problems, which though requires more researches to
      corroborate. This investigation was conducted to ascertain the relationship
      between yoga and meniscus injury as well as the extent of impairment according to
      variant yoga practice periods. METHODS: Totally 819 women aged 20-49 years who
      practiced yoga or other popular sports including badminton, jogging, climbing
      hills, etc for at least one hour per day were selected to participate in this
      research. These subjects were required to complete a questionnaire and receive
      relevant physical examination. Magnetic resonance (MR) scan of the knee was
      recommended for the suspicious subjects for ultimate diagnosis. The subject with
      abnormal meniscus MR signals was defined as a case and matched with two controls
      in terms of age and body mass index (BMI). Altogether there were 273 cases and
      546 controls. The nested case-control model was adopted to assess the risk of
      meniscus injury between variant exposures in practicing yoga and several other
      popular sports. Moreover, the 181 yoga subjects were subdivided into three groups
      according to different exercise durations, followed by further analysis with the
      variables of age, BMI and Lysholm score. RESULTS: Yoga was found associated with
      a higher risk (P equal to 0.008, OR equal to 1.621) of meniscus injury compared
      with badminton, jogging and climbing hills. The three yoga subgroups showed
      statistical difference between each other in terms of Lysholm score (P equal to
      0.027) and BMI (P equal to 0.003). The subjects with longer-term yoga practice
      had lighter weight but lower Lysholm scores. CONCLUSIONS: Yoga perhaps exerts
      destructive impact on the meniscus for Chinese women, yet it needs further
      verifications. Furthermore, the female yoga players with longer exercise duration
      are more susceptible to meniscus injury though they can become leaner.

PMID- 22663909
TI  - Does mismatch of the femoral component aspect ratio influence the range of knee
      flexion after posterior-stabilized total knee arthroplasty?
AB  - OBJECTIVE: To study whether the range of knee flexion (ROF) is affected by
      geometrical mismatch of the femoral component and the resultant change in the
      posterior condylar offset (PCO) after high-flexion posterior-stabilized total
      knee arthroplasty (TKA). METHODS: One hundred osteoarthritic patients (50 males
      and 50 females) underwent femoral osteotomy by the anterior referencing
      technique. The PCO for each patient was measured from lateral radiographs before,
      during and 2 years after TKA. The thickness of the joint cartilage was measured
      by magnetic resonance imaging before TKA and added onto the radiographic
      measurement. The relationship between changes in the PCO and improvements in the
      ROF before, during and 2 years after TKA were statistically analyzed. RESULTS:
      Compared with the preoperative value, the PCO was reduced by (3.45+/-3.28) mm
      after TKA, with a significantly larger reduction observed in female patients than
      male patients (P less than 0.05). When examining the subject population as a
      whole, there was a significant positive correlation between PCO and ROF
      improvement during TKA (P less than 0.05), but this improvement was not
      maintained 2 years after TKA (P larger than 0.05). However, when male and female
      patients were analyzed separately, there was a significant positive correlation
      between PCO change and ROF improvement for both sexes at both time points (all P
      less than 0.05). CONCLUSIONS: Restoration of PCO plays an important role in the
      optimization of knee flexion even after posterior-stabilized TKA. Femoral
      components based on Caucasian anatomic characteristics could not match the native
      anatomy of distal femurs in Chinese population especially female Chinese. Rotated
      resection of distal femur with anterior re-ferencing technique usually leads to a
      decreased PCO and therefore reduces maximal obtainable flexion.

PMID- 22663910
TI  - Decompressive craniectomy or not: intraoperative experience in 41 patients with
      severe traumatic brain injury.
AB  - OBJECTIVE: To present our experience in using decompressive craniectomy (DC)
      among severe traumatic brain injury (TBI) patients during operation and to
      discuss its indication. METHODS: From October 2008 to May 2009, 41 patients aged
      between 18 and 75 years with severe TBI were included in this study. They
      underwent DC or non-DC (NDC) according to their intraoperative findings.
      Postoperative intracranial pressure (ICP), complications, requiring second
      operation or not and outcomes were observed. RESULTS: Fifteen patients underwent
      DC and 26 patients did not. The average postoperative ICP of each patient was
      lower than 20 mm Hg. For patients received DC, 2 had seizures after operation and
      1 developed cerebrocele in the follow-up period; only 1 NDC patient had post
      traumatic seizures, but none of them had delayed haematoma, cerebrospinal fluid
      fistula, cerebrocele or infections. At the end of follow-up, 10 patients died, 6
      had the GOS of 2, 2 of 3, 9 of 4 and 14 of 5. CONCLUSIONS: DC is necessary to
      manage fulminant intracranial hypertension or intraoperative brain swelling. If
      there was not brain swelling after removal of the haematoma and necrotized neural
      tissues, it is safe to replace skull flap. The intraoperative finding is an
      important factor to decide whether to perform DC or not.

PMID- 22663911
TI  - Civilian casualties of Iraqi ballistic missile attack to Tehran, capital of Iran.
AB  - OBJECTIVE: To determine the pattern of causalities of Iraqi ballistic missile
      attacks on Tehran, the capital of Iran, during Iraq-Iran war. METHODS: Data were
      extracted from the Army Staff Headquarters based on daily reports of Iranian army
      units during the war. RESULTS: During 52 days, Tehran was stroked by 118 Al
      Hussein missiles (a modified version of Scud missile). Eighty-six missiles landed
      in populated areas. During Iraqi missile attacks, 422 civilians died and 1 579
      injured (4.9 deaths and 18.3 injuries per missile). During 52 days, 8.1 of the
      civilians died and 30.4 injured daily. Of the cases that died, 101 persons (24%)
      were excluded due to the lack of information. Among the remainders, 179 (55.8%)
      were male and 142 (44.2%) were female. The mean age of the victims was 25.3
      years+/-19.9 years. Our results show that the high accuracy of modified Scud
      missiles landed in crowded areas is the major cause of high mortality in Tehran.
      The presence of suitable warning system and shelters could reduce civilian
      casualties. CONCLUSION: The awareness and readiness of civilian defense forces,
      rescue services and all medical facilities for dealing with mass casualties
      caused by ballistic missile attacks are necessary.

PMID- 22663912
TI  - Flexion/extension cervical spine views in blunt cervical trauma.
AB  - OBJECTIVE: To examine the contribution of flexion and extension radiographs in
      the evaluation of ligamentous injury in awake adults with acute blunt cervical
      spine trauma, who show loss of cervical lordosis and neck pain. METHODS: All
      patients who presented to our emergency department following blunt trauma were
      enrolled in this study, except those with schiwora, neurological deficits or
      fracture demonstrated on cross-table cervical spine X-rays, and those who were
      either obtunded or presented after cervical spine surgery. Adequacy of flexion
      and extension views was checked by the neurosurgery and radiology team members.
      All these patients underwent cross-table cervical spine view followed by
      flexion/extension views based on the loss of lordosis on cross-table imaging and
      the presence of neck pain. RESULTS: A total of 200 cases were reviewed, of whom
      90 (45%) underwent repeat X-rays because of either inadequate exposure or limited
      motion. None of the patients with loss of lordosis on cross-table view had
      positive flexion and extension views of cervical spine for instability.
      CONCLUSIONS: Our results show that in patients who underwent acute radiographic
      evaluation of blunt cervical spine trauma, flexion and extension views of the
      cervical spine are unlikely to yield positive results in the presence of axial
      neck pain and/or loss of cervical lordosis. We can also hypothesize that
      performing flexion and extension views will be more useful once the acute neck
      pain has settled.

PMID- 22663913
TI  - Analysis of 86 fatal motorcycle frontal crashes in Chongqing, China.
AB  - OBJECTIVE: To analyze the injuries of motorcyclists involved in fatal motorcycle
      frontal crashes. METHODS: A survey group involving multi-discipline experts was
      built to randomly collect data on fatal motorcycle frontal collision accidents
      that occurred in Chongqing during 2006-2010. The sampled information included
      medical or autopsy reports, blood alcohol concentration (BAC) level, helmet use,
      accident witness, field sketch as well as field photos. The motorcyclist injuries
      were scored according to the Abbreviated Injury Scale (AIS) 2005. The involved
      riders with a BAC level larger than or equal to 20 mg/ml were attributed to
      alcohol use. Data were processed statistically with nonparametric test via
      software SPSS 11.0. RESULTS: A total of 86 fatal motorcycle frontal crashes were
      sampled and further analyzed. The age of motorcyclists enrolled in this
      investigation showed nominal distribution and the middle-aged (30-39 years)
      occupied the highest percentage of fatalities. There were only 14 motorcyclists
      (16.3%) wearing helmets at the moment of collision. And 12.8% of these
      motorcyclist crashes were attributable to alcohol use. Impact injury was the main
      fatal cause, accounting for 72% of motorcyclist deaths, followed by tumbling
      injury  (26%) and run-over (2%). Respectively 84%, 22% and 19% of motorcyclists
      who sustained head, chest and abdominal trauma died. Extremity injury was the
      most frequently observed injury type. CONCLUSIONS: This investigation is helpful
      to build accident prevention programs and develop protection devices which may
      effectively mitigate injuries and prevent deaths following motorcycle frontal
      collision accidents. Further investigations on motorcycle collision accidents are
      still needed.

PMID- 22663914
TI  - Anatomic double-bundle anterior cruciate ligament reconstruction.
AB  - OBJECTIVE: To retrospectively evaluate the early results of anatomic double
      bundle anterior cruciate ligament (ACL) reconstruction and compare with the
      results of native ACL of the contralateral knee. METHODS: The results of a
      consecutive series of 118 patients receiving arthroscopic ACL reconstruction were
      evaluated. Eight patients were lost to the latest follow-up, leaving a total of
      110 patients available for study within at least 3 years'clinical follow-up.
      Among them, 63 patients underwent postoperative MRI and CT scan, as well as
      clinical evaluation. RESULTS: After reconstruction, the knees were stable and
      pain-free.  Mean postoperative Lysholm score was 95.54 in 110 patients after 3
      years. CT and MRI assessment showed that the reconstruction centered in the
      femoral footprint of ACL (n equal to 63). The sagittal ACL angle in the
      reconstructed ACL (52.16 degree+/-2.45 degree was much close to that in the
      contralateral intact ACL (51.31 degree +/-2.18 degree, P larger than 0.05). By
      ACL-Blumensaat line angle analysis, there was no difference between double-bundle
      reconstructed knees and their contralateral normal knees (4.67 degree+/-0.43
      degree vs. 4.62 degree+/-0.60degree, P larger than 0.05). CONCLUSION: Anatomic
      double-bundle ACL reconstruction can place grafts more precisely in the anatomic
      footprint of the ACL and better restore knee kinematics.

PMID- 22663915
TI  - Treatment of 336 cases of chest trauma.
AB  - OBJECTIVE: To summarize the clinical features, diagnosis and treatment of chest
      trauma. METHODS: A retrospective analysis was conducted among 336 cases of chest
      trauma admitted to our hospital from January 2009 to May 2011. RESULTS: Out of
      all cases, 325 were cured, accounting for 96.7%; 11 died, accounting for 3.3%.
      Among the dead cases, one died of hemorrhagic shock, three of acute respiratory
      distress syndrome, three of multiple organ failure, and four of severe multiple
      traumas. CONCLUSIONS: (1) For patients with severe chest trauma, early emergency
      treatment is crucial to save life. (2) Open thoracic surgery is needed for acute
      cardiac tamponade, intrapulmonary vascular injuries, progressive intrathoracic
      bleeding, lung laceration, tracheal breakage, and diaphragmatic injury. In
      addition, operative timing and method should be well chosen. (3) Pulmonary
      contusion is one of common complications in chest trauma, for which the
      combination of strong anti-infection therapy and mechanical ventilation is an
      effective treatment strategy.

PMID- 22663916
TI  - Influence of apolipoprotein E and its receptors on cerebral amyloid precursor
      protein metabolism following traumatic brain injury.
AB  - Traumatic brain injury (TBI) is the leading cause of mortality and disability
      among young individuals in our society, and globally the incidence of TBI is
      rising sharply. Mounting evidence has indicated that apolipoprotein E (apoE:
      protein; APOE: gene) genotype influences the outcome after TBI. The proposed
      mechanism by which APOE affects the clinicopathological consequences of TBI is
      multifactorial and includes amyloid deposition, disruption of lipid distribution,
      dysfunction of mitochondrial energy production, oxidative stress and increases
      intracellular calcium in response to injury. This paper reviews the current state
      of knowledge regarding the influence of apoE and its receptors on cerebral
      amyloid beta-protein precursor metabolism following TBI.

PMID- 22663917
TI  - Bilateral traumatic patellar fracture: a case report and review of literature.
AB  - Simultaneous isolated bilateral patellar fractures are very rare injuries and
      most often associated with systemic disorders such as hyperparathyroidism,
      osteoporosis, stress fracture and kidney failure. Isolated bilateral traumatic
      fracture of patella following an unusual mode of injury is seldomly reported in
      the literature. We reported such a case following a road traffic accident without
      any associated injuries or co-morbid condition. The patella on the right side had
      transverse open fracture which was fixed with two Kirschner wires following
      tension band principle, and that on the left side sustained upper pole
      comminution which was treated by partial patellectomy. The patient achieved good
      outcome: at 6 months he was able to squat and sit cross legged; at one year he
      obtained nearly normal muscle strength and full range of motion. We discussed the
      injury mechanism, management and rehabilitation in such a case and reviewed the
      available literature regarding such a presentation.

PMID- 22663919
TI  - Cocoa modulatory effect on rat faecal microbiota and colonic crosstalk.
AB  - Previous studies have reported the effect of a cocoa-enriched diet on the
      intestinal immune system in rats. Cocoa contains fibre and polyphenols that can
      directly influence the intestinal ecosystem and its relationship with the immune
      system. The aim of this study was to evaluate the effects of a cocoa-enriched
      diet on gut microbiota, toll-like receptor (TLR) expression and immunoglobulin
      (Ig) A (IgA) intestinal secretion in rats. Four-week-old Wistar rats were fed a
      standard or cocoa diet for 6 weeks. Faecal samples were collected before the
      beginning of the diet and at the end of the study. After the nutritional
      intervention, colon samples were obtained to quantify TLR and IgA gene expression
      and IgA protein. Microbiota composition was characterized by fluorescent in situ
      hybridization (FISH) coupled to flow cytometry (FCM) analysis using specific
      probes directed to 16S rRNA of the main bacteria genus present in rat intestine.
      The cocoa dietary intervention resulted in a differential TLR pattern and a
      decrease in the intestinal IgA secretion and IgA-coating bacteria. Moreover there
      was a significant decrease in the proportion of Bacteroides, Clostridium and
      Staphylococcus genera in the faeces of cocoa-fed animals. In conclusion, cocoa
      intake affects the growth of certain species of gut microbiota in rats and is
      associated with changes in the TLR pattern which could be responsible for the
      changes observed in the intestinal immune system.

PMID- 22663918
TI  - Hand hygiene opportunities in pediatric extended care facilities.
AB  - INTRODUCTION: Introduction: Children in extended care facilities (ECFs) are at
      risk of healthcare-associated infections, but little hand hygiene (HH) research
      has been conducted in this unique setting. METHODS: Eight children across four
      pediatric ECFs were observed for a cumulative 128 hours, and all care giver HH
      opportunities were characterized by the World Health Organization's '5 Moments
      for HH'. Data were analyzed using Pearson's chi2 test. RESULTS: Observers
      documented 865 HH opportunities. Overall HH adherence was 43% and was
      significantly higher among clinical care givers than among non-clinical care
      givers (61% and 14%, respectively, (p < .01). CONCLUSIONS: Hand hygiene adherence
      was low, suggesting multiple opportunities for transmission of infectious agents.

PMID- 22663920
TI  - [A comparison of the long-term efficacy of cochlear implantation at early and
      late age].
AB  - OBJECTIVES: This study aims to investigate the effects of age factor on the long
      term efficacy of cochlear implantation. PATIENTS AND METHODS: The electronic
      records of patients, who underwent cochlear implantation with the initial
      diagnosis of bilateral severe to profound sensorineural hearing loss in our
      clinic between January 2001 and December 2008, were analyzed retrospectively. The
      patients were divided into two groups according to their age at the time of
      cochlear implantation, including group 1 with the patients less than four years
      of age and group 2 with the patients more than four years of age. Groups were
      evaluated and compared for the in terms of demographic characteristics,
      Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR)
      at three years following surgery. RESULTS: A total of 37 patients underwent
      cochlear implantation. Of them, 18 patients (48.6%) were operated at less than
      four years of age, while 19 patients (51.4%) were operated at more than four
      years of age. No significant difference was found between the groups in terms of
      sex, educational level and profession of the parents, operated side and duration
      of implant use. According to CAP and SIR categories, group 1 patients had
      statistically significantly higher level of the CAP and SIR categories (p=0.009
      and p<0.001 respectively). CONCLUSION: Our study results suggested that the age
      of cochlear implantation has significant effects on long-term hearing and speech
      abilities. Cochlear implantation carried out at earlier ages (<4) enhances more
      satisfactory results in terms of long-term efficacy.

PMID- 22663921
TI  - Oncologic and functional outcomes of open surgery in early supraglottic tumors:
      is it still a valid technique?
AB  - OBJECTIVES: In this study, we aimed to analyze the oncologic and functional
      outcomes of supraglottic laryngectomy. PATIENTS AND METHODS: Medical records of
      91 cases (85 males, 6 females; mean age 55.4 years; range 30 to 75 years) who
      underwent surgery due to early supraglottic laryngeal cancer in our clinic were
      retrospectively analyzed. Statistical analysis was performed using chi-square
      test and Fisher's exact test. Mean values were estimated by means of t-test,
      while survival curves were drawn using Kaplan-Meier method. RESULTS: With respect
      to oncologic assessment, disease-free survival rate was 81%, the rate of regional
      recurrence was 6%, the rate of local recurrence was 8%, the rate of distant
      metastasis was 7% and the rate of occult neck metastasis was 25%. Metastatic neck
      disease and extracapsular invasion in the lymphatic ganglia were found to be the
      most critical parameters in terms of survival. With respect to functional
      assessment, the mean time of decannulation was 41 days, while the mean time of
      nasogastric tube removal was 19 days. It was observed that cases with a Forced
      Expiratory Volume in 1 second (FEV-1) of <75% experienced more aspiration-related
      problems. The functional outcomes were worse in the cases who underwent bilateral
      neck dissection and postoperative radiotherapy. CONCLUSION: Open surgery is a
      more effective treatment modality in the early supraglottic tumors in terms of
      oncologic and functional outcomes. It should be continued to be use as an
      alternative method to the novel and expensive technologies including transoral
      robotic surgery or transoral laser surgery.

PMID- 22663922
TI  - [Our results of endoscopic dacryocystorhinostomy and bicanalicular silicone tube
      intubation surgery].
AB  - OBJECTIVES: In this study, we evaluated the results of endoscopic
      dacryocystorhinostomy and bicanalicular silicone tube intubation (EDCR + BSTI)
      surgery in the patients with epiphora due to nasolacrimal duct obstruction.
      PATIENTS AND METHODS: A total of 120 eyes in 112 patients (40 males, 72 females;
      mean age 42; range 6 to 74 years) who underwent EDCR + BSTI surgery under general
      anesthesia between August 2006 and December 2010 were analyzed retrospectively.
      RESULTS: Of the patients, 104 underwent unilateral surgery, while eight underwent
      bilateral surgery. One hundred nine of 120 surgeries were primary, whereas 11
      were revision surgery. Follow-up was performed on a regular basis in the first
      week, at one, three, six, and 12 months following surgery. Successful results
      were obtained in 113 of 120 operation, however seven patients required revision
      surgery. Repeated EDCR + BSTI surgery gave successful results in all cases, as
      assessed during the follow-up visits. CONCLUSION: EDCR + BSTI surgery is a
      primary treatment of choice for the patients with epiphora due to nasolacrimal
      duct obstruction with a high success rate.

PMID- 22663923
TI  - Symptomatology and etiology of chronic pediatric rhinosinusitis.
AB  - OBJECTIVES: This study aims to define symptoms and etiology and determine how to
      prevent chronic rhinosinusitis in children. PATIENTS AND METHODS: Between
      February 2003 and February 2005, 50 pediatric patients (25 girls and 25 boys;
      mean age 8.22 years; range 4 to 14 years) with chronic rhinosinusitis were
      included in the study. The patients were questioned about anterior/posterior
      nasal dripping, night cough, headache, nausea, vomiting and nasal obstruction for
      symptomatology; about school condition, smoking behavior of parents and history
      of asthma for etiology. Hemogram, serum biochemistry, allergy test, nasal smear,
      chest and lateral neck radiography and sweat test were performed. RESULTS:
      Symptomatologic examination revealed that 48% had anterior nasal dripping, 62%
      with postnasal dripping, 70% with headache and 90% with nasal obstruction.
      Evaluation of etiological factors revealed that 68% were going to school, 48% of
      the parents had the history of smoking, 42% with allergy test-positivity and 60%
      with adenoid vegetation. CONCLUSION: Our study results indicated that
      environmental factors are important as etiological factors in rhinosinusitis. For
      prevention, we recommend restriction of close relationship at school, not to
      smoke at home and vaccination in each year with influenza and S. pneumonia
      vaccine.

PMID- 22663924
TI  - [Minimally invasive video-assisted thyroidectomy for treatment of benign thyroid
      nodules].
AB  - OBJECTIVES: This study aims to evaluate patients who underwent minimally invasive
      video-assisted thyroidectomy (MIVAT) and to discuss the advantages and
      disadvantages of this technique in the light of literature data. PATIENTS AND
      METHODS: Between May 2008 and February 2009, 20 patients (18 females, 2 males;
      mean age 44.5+/-13.6 years; range 23 to 68 years) who underwent MIVAT using a 4
      mm and 30 degrees  rigid endoscope and ultrasonic scalpel for dissected the main
      thyroid vessels were included in the study. Inclusion criteria were benign
      thyroid nodules of <30 mm and ultrasonographically thyroid volume of <20 ml.
      RESULTS: The mean length of incision was 2.6+/-0.5 cm, the mean operation time
      was 111.7+/-39.7 min and the mean amount of bleeding was 82.8+/-84.1 cc. A
      statistically significantly positive relationship was found between the operation
      time and the nodule size and the amount of bleeding and also between the length
      of the incision and cosmetic satisfaction scale scores (p<0.05). However, no
      statistically significant correlation was found between the operation time and
      postoperative pain and between the length of incision and postoperative pain
      (p>0.05). Although 30% of the patients had mild to moderate pain, 50% had
      moderate pain and 20% had severe pain in the early postoperative period, no
      patient had pain in the postoperative third day. No postoperative persistent
      vocal cord paralysis was observed in the patients. CONCLUSION: Minimally invasive
      video-assisted thyroidectomy is a safe and useful approach in the treatment of
      the patients with benign thyroid nodules.

PMID- 22663925
TI  - [Self and significant other assessment of hearing device aided communication
      skills in the elderly with hearing loss].
AB  - OBJECTIVES: This study aims to evaluate the communication problems of elderly
      before and after using hearing aids. PATIENTS AND METHODS: Thirty hearing aid
      users and 10 normal hearing control subjects with their relatives were enrolled
      in the study. Hearing aid users were divided into three subgroups based on the
      duration of use. Self Assessment of Communication (SAC) and Significant Other
      Assessment of Communication (SOAC) questionnaires were administered to hearing
      aid users, control subjects, as well as to their relatives for the evaluation of
      communication difficulties due to hearing loss. Intra-group comparisons were
      carried out in the patients using hearing aids, while inter-group comparisons
      were performed to evaluate the effects of different aided periods on
      communication skills. RESULTS: It was found that the communication difficulties
      reduced in the patients who used hearing aid for minimum one month. For the
      patients with hearing loss, hearing aid use of six months or more increased SAC
      and SOAC scores to a level comparable with control subjects. CONCLUSION: The
      present study conclude that the elderly patients of 60 years of age or more with
      moderate sensorineural hearing loss could catch up their normal hearing peers in
      their communication skills within six months only if they prescribed and used
      proper hearing aids.

PMID- 22663926
TI  - Papillary thyroid carcinoma with metastasis to the temporooccipital skull: a case
      report.
AB  - The patient was admitted to our clinic with the complaint of swelling in his left
      post-auricular region. The medical history revealed that he underwent thyroid
      surgery eight years ago and the specimen was reported as papillary thyroid
      carcinoma. Following required analyses, total thyroidectomy and biopsy from
      mastoid region were performed. Total thyroidectomy specimen was proved thyroid
      papillary microcarcinomas at five foci of the thyroid gland, while biopsy samples
      obtained from the mastoid region were reported as metastatic papillary thyroid
      carcinoma. The patient underwent radioactive iodine, followed by radiotherapy. In
      this article, we present a 61-year-old male patient with papillary thyroid
      carcinoma metastatic to the temporooccipital region, accompanied by multiple
      cranial nerve paralysis.

PMID- 22663927
TI  - [Sinonasal extranodal natural killer/T-cell lymphoma: a case report and review of
      recent developments in the management].
AB  - Nasal extranodal natural killer/T-cell lymphoma, which is a highly aggressive
      disease, is more frequently seen in Asia than in Western countries. No consensus
      has been reached on the management of the disease and the survival depends on the
      stage of the disease. Localized NK/T-cell lymphoma often responds to radiotherapy
      well. However, patients with advanced disease or recurrence after
      chemoradiotherapy, similar to our patient, have a very poor prognosis. In this
      article, we present a 52-year-old male patient with early recurrence and who was
      refractory to chemotherapy. The management of the disease was reviewed in the
      light of the recent literature data.

PMID- 22663928
TI  - [A parotid gland lymphoma presenting with steroid-responsive recurrent
      sialadenitis: a case report].
AB  - Parotid gland located lymphomas are rarely seen. The most common lymphomas
      involving salivary gland include B-cell MALT (mucosa-associated lymphoid tissue)
      lymphomas. Of them, extranodal marginal zone B-cell lymphomas are the most
      frequently seen pathologies. They usually present with painless swelling of the
      parotid gland. The diagnosis is often based on parotidectomy. In this article, we
      report a 46-year-old male patient who was admitted with recurrent sialadenitis
      attacks which responded well to steroid treatment for three years, but recur
      after the cessation of the therapy. With the initial diagnosis of recurrent
      parotitis, the patient was scheduled for total parotidectomy for the definitive
      diagnosis and treatment. When the frozen-section of specimens during superficial
      parotidectomy revealed lymphoma, the operation was terminated.

PMID- 22663929
TI  - Recurrent glandular odontogenic cyst treatment.
AB  - The glandular odontogenic cyst (GOC) is a rare odontogenic cyst. Although none of
      the clinical or radiographic features of GOC are unique or pathognomonic, the
      lesion has a potentially aggressive behavior. Treatment of GOC includes curettage
      and enucleation or excision and cryotherapy; however marginal resection is
      usually considered a more reliable approach due to the low incidence of
      recurrence. In this article, we present a case with GOC which recurred five years
      after the initial surgical treatment.

PMID- 22663930
TI  - Progressive swelling and radiopaque mass in maxillary sinus: formation of stone.
AB  - Although radiopaque lesions located in the maxillary sinus are rare, differential
      diagnosis should include a number of pathologies. Formation of stone, namely
      "antrolith" in the paranasal sinuses is a very rare phenomenon and it should be
      considered in the differential diagnosis, as it is usually located in the
      maxillary sinus. In this article, we present a 47-year-old male case with
      unilateral chronic sinusitis for a long time and calcification in maxillary sinus
      in the light of clinical/radiographic findings of the lesion and treatment
      strategy.

PMID- 22663931
TI  - A giant mixed tumor originating from the parapharyngeal space.

PMID- 22663932
TI  - A rapid, novel model of culturing cranial nerve X-derived motoneurons for
      screening trophic factor outgrowth response.
AB  - OBJECTIVES: After cranial nerve X (CN X) injury, vocal fold paralysis treatments
      currently face a myriad of obstacles in achieving non-synkinetic, functional
      reinnervation. Of particular therapeutic interest is the targeted administration
      of locally expressed biological neurotrophic factors (NFs). To date, a method to
      culture mature CN X motoneurons for NF responsiveness screening has not been
      described. METHODS: We herein present a novel method for establishing mature
      murine CN X motoneuron cultures, and use the model to test CN X motoneuron
      outgrowth response to individual and paired ascending concentrations of selected
      neurotrophic factors [glial cell-derived neurotrophic factor (GDNF), brain
      derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF)].
      RESULTS: Findings demonstrated low concentration (5 ng/ml) CNTF to have the
      greatest positive effect on motoneuron outgrowth, beyond that of both indivual NF
      and paired NF combinations, based on total neurite outgrowth [mean total neurite
      outgrowth = 445.7+/-84.45 MUm in the (5 ng/ml) CNTF group versus 179.7+/-13.63
      MUm in saline controls (P<0.01)]. Paired treatments with CNTF/GDNF, and CNTF/BDNF
      promoted motoneuron branching at a variety of concentrations beyond saline
      controls, and paired GDNF/BDNF had inhibitory effects on motoneuron branching.
      DISCUSSION: Our described in vitro model of establishing mature CN X cultures
      allowed rapid screening for responsiveness to therapeutic NFs at a variety of
      concentrations and combinations. While the model ultimately may be used to
      investigate the molecular mechanisms of CN X motoneuron regeneration, the current
      study identified CNTF as a promising therapeutic candidate for the promotion of
      CN X outgrowth.

PMID- 22663933
TI  - Hemorrhage risk after partial endovascular NBCA and ONYX embolization for brain
      arteriovenous malformation.
AB  - OBJECTIVE: To estimate for hemorrhage risk of partially endovascularly embolized
      brain arteriovenous malformation (BAVM). METHODS: We retrospectively reviewed 147
      consecutive patients with BAVM-treated mainly with endovascular N-butyl
      cyanoacrylate (NBCA) and ONYX embolization. In Kaplan-Meier survival analysis,
      the index date was the dated of initial endovascular embolization; cases were
      censored at time of subsequent intracranial hemorrhage (ICH), or loss to follow
      up, and multivariate proportional-hazards regression models included age of
      presentation (<=30 years old), clinical presentations, and other potential
      confounders. RESULTS: We reviewed 147 patients with BAVM (58.8% male; mean age+/
      SD at treatment: 27.5+/-11.1 years) treated with endovascular embolization. One
      hundred and forty-four NBCA and 76 ONYX embolizations were performed. Complete
      obliteration of BAVMs was achieved in 29 patients (19.7%). Thirty-two (21.8%)
      patients were treated with additional Gamma-knife radiosurgery. During 499.5
      years of follow-up, 15 partially treated patients suffered a further hemorrhage,
      which caused four deaths. The crude annual risk of hemorrhage was 3.0% and the
      annual death rate was 0.8%. Among partially treated patients with hemorrhage at
      initial presentation, the risk of hemorrhage was 3.8%, while the risk of
      hemorrhage for patients without hemorrhage at initial presentation was 2.5%. The
      annual rate of subsequent hemorrhage was 2.6% for non-ICH and 4.2% for ICH in the
      partial NBCA embolization group compared with 2.4% for non-ICH and 2.4% for ICH
      in the partial ONYX embolization group. CONCLUSIONS: The effect of partial AVM
      embolization with liquid embolic agents may still be unclear as for risk
      reduction of annual hemorrhage rate of cerebral AVM.

PMID- 22663935
TI  - Frailty and the role of inflammation, immunosenescence and cellular ageing in the
      very old: cross-sectional findings from the Newcastle 85+ Study.
AB  - Age-related frailty is an increasing societal challenge with growing emphasis on
      identifying its underlying pathophysiology and prospects for intervention. We
      report findings from the first comprehensive study of frailty and biomarkers of
      inflammation, immunosenescence and cellular ageing in the very old. Using cross
      sectional data from the Newcastle 85+ Study (n=845, aged 85), frailty was
      operationalized by the Fried and Rockwood models and biomarker associations
      explored using regression analysis. We confirmed the importance of inflammatory
      markers (IL-6, TNF-alpha, CRP, neutrophils) in frailty in the very old,
      previously established only in younger-old populations. Limited evidence was
      found for immunosenescence in frailty; although total lymphocyte count was
      inversely related, no association was found with the immune risk profile and the
      inverse associations observed with memory/naive CD8 T and B cell ratios were in
      the opposite direction to that expected. We found no association with frailty in
      the very old for CMV sero-positivity, telomere length, markers of oxidative
      stress or DNA damage and repair. The Fried and Rockwood frailty models measure
      different albeit overlapping concepts yet biomarker associations were generally
      consistent between models. Difficulties in operationalizing the Fried model, due
      to high levels of co-morbidity, limit its utility in the very old.

PMID- 22663934
TI  - Effects of social isolation on glucocorticoid regulation in social mammals.
AB  - The regulation and function of the hypothalamic-pituitary-adrenocortical (HPA)
      axis and glucocorticoids have been well conserved across vertebrate species.
      Glucocorticoids influence a wide range of physiological functions that include
      glucose regulation, metabolism, inflammatory control, as well as cardiovascular,
      reproductive, and neuronal effects. Some of these are relatively quick-acting non
      genomic effects, but most are slower-acting genomic effects. Thus, any stimulus
      that affects HPA function has the potential to exert wide-ranging short-term and
      long-term effects on much of vertebrate physiology. Here, we review the effects
      of social isolation on the functioning of the HPA axis in social species, and on
      glucocorticoid physiology in social mammals in particular. Evidence indicates
      that objective and perceived social isolation alter HPA regulation, although the
      nature and direction of the HPA response differs among species and across age.
      The inconsistencies in the direction and nature of HPA effects have implications
      for drawing cross-species conclusions about the effects of social isolation, and
      are particularly problematic for understanding HPA-related physiological
      processes in humans. The animal and human data are incommensurate because, for
      example, animal studies of objective isolation have typically not been modeled
      on, or for comparability with, the subjective experience of isolation in humans.
      An animal model of human isolation must be taken more seriously if we want to
      advance our understanding of the mechanisms for the effects of objective and
      perceived isolation in humans.

PMID- 22663936
TI  - The role of autonomic nervous system in the pathophysiology of hemifacial spasm.
AB  - OBJECTIVES: Despite the vascular compression of the seventh cranial nerve has
      been verified by the microvascular decompression surgery as the cause of
      hemifacial spasm (HFS), the mechanism of the disease is still unknown. We believe
      that the autonomic nervous system in adventitia of the offending artery may
      contribute to the HFS. To prove our hypothesis, we performed an experiment in SD
      rats. METHODS: Moller's HFS model was adopted and the abnormal muscle response
      (AMR) wave was electrophysiologically monitored. With randomization, some HFS
      rats underwent exclusion of the offending artery or removal of the ipsilateral
      superior cervical ganglion. Some HFS rats with negative AMR following exclusion
      of the offending artery were dripped with norepinephrine onto the neurovascular
      conflict site. RESULTS: With exclusion of the offending artery, AMR disappeared
      in 14 (70%) of the 20 HFS rats, while in three (30%) of the 10 from sham
      operation group (P<0.05). With ganglionectomy, AMR disappeared in 12 (75%) of the
      16 HFS rats, while in two (25%) of the eight from the sham operation group
      (P<0.05). With norepinephrine drip, AMR reappeared in four (67%) of the six from
      those offending-artery-excluded HFS rats, while in zero of the six from normal
      saline-dripped group (P<0.05). DISCUSSION: The neurotransmitter releasing from
      the autonomic nervous endings in the worn adventitia of the offending artery may
      induce an ectopia action potential in those demyelinated facial nerve fibers
      expanding to the neuromuscular conjunction and trigger an attack of HFS.

PMID- 22663938
TI  - Cancer patterns in Inuit Nunangat: 1998-2007.
AB  - OBJECTIVES: To compare cancer incidence patterns between residents of Inuit
      Nunangat and the rest of Canada. STUDY DESIGN: Cancer cases were geographically
      linked to either Inuit Nunangat or the rest of Canada using postal codes or other
      geographic information. Population estimates were derived from the 2001 and 2006
      censuses. METHODS: Cancer cases were combined from 1998 to 2007 for Inuit
      Nunangat and the rest of Canada. Age-standardised incidence rates were calculated
      for all site cancers and sub-sites by sex. Standardised rate ratios between these
      2 areas were calculated for all site cancers and sub-sites. RESULTS: The age
      standardised incidence rate for all cancer sites (1998-2007) was 14% lower for
      the Inuit Nunangat male population and 29% higher for the female population by
      comparison to the rest of Canada. Cancers of the nasopharynx, lung and bronchus,
      colorectal, stomach (males), and kidney and renal pelvis (females), were elevated
      in the Inuit Nunangat population compared to the rest of Canada, whereas prostate
      and female breast cancers were lower in the Inuit Nunangat population.
      CONCLUSIONS: Cancers with potentially modifiable risk factors, such as buccal
      cavity and pharynx, nasopharynx, lung and bronchus, and colorectal cancer were
      elevated in the Inuit Nunangat population compared to the rest of Canada. Besides
      greater smoking prevalence within Inuit Nunangat by comparison to the rest of
      Canada, distinct socioeconomic characteristics between respective area
      populations including housing, and income may have contributed to incidence
      differentials. This study demonstrated that a geographic approach can be used in
      cancer surveillance when populations of interest are spatially distinguishable,
      and reside across distinct jurisdictions whose combined cancer registries will
      not completely provide information to identify the population of interest.

PMID- 22663937
TI  - Self-rated health and ethnicity: focus on indigenous populations.
AB  - OBJECTIVES: Self-rated health (SRH) is a commonly used measure in surveys to
      assess general health status or health-related quality of life. Differences have
      been detected in how different ethnic groups and nationalities interpret the SRH
      measure and assess their health. This review summarizes the research conducted on
      SRH within and between ethnic groups, with a focus on indigenous groups. STUDY
      DESIGN AND METHODS: A search of published academic literature on SRH and
      ethnicity, including a comprehensive review of all relevant indigenous research,
      was conducted using PubMed and summarized. RESULTS: A wide variety of research on
      SRH within ethnic groups has been undertaken. SRH typically serves as an outcome
      measure. Minority respondents generally rated their health worse than the
      dominant population. Numerous culturally-specific determinants of SRH have been
      identified. Cross-national and cross-ethnicity comparisons of the associations of
      SRH have been conducted to assess the validity of SRH. While SRH is a valid
      measure within a variety of ethnicities, differences in how SRH is assessed by
      ethnicities have been detected. Research in indigenous groups remains generally
      under-represented in the SRH literature. CONCLUSIONS: These results suggest that
      different ethnic groups and nationalities vary in SRH evaluations, interpretation
      of the SRH measure, and referents employed in rating health. To effectively
      assess and redress health disparities and establish culturally-relevant and
      effective health interventions, a greater understanding of SRH is required,
      particularly among indigenous groups, in which little research has been
      conducted.

PMID- 22663939
TI  - Living conditions, quality of life, adherence and treatment outcome in
      Greenlandic HIV patients.
AB  - OBJECTIVES: Despite a high level of sexually transmitted infections, HIV
      incidence has remained quite stable in Greenland with 5-6 new cases per year
      (approximately 10 per 100,000). However, disease control is suboptimal and
      mortality is relatively high. The aim of the present study was to determine
      associations between adherence to treatment and treatment outcome, living
      conditions and quality of life among HIV patients in Greenland. MATERIAL AND
      METHODS: Cross-sectional questionnaire-based cohort study of HIV patients in
      Greenland during 2008-2009. Data regarding treatment, viral load, CD4 count, etc.
      were obtained from a central HIV-database. RESULTS: Forty-six persons, 17 women
      and 29 men, of the 60 registered HIV-positive patients (77%) were included.
      Eighty percent were heterosexually infected and 17% by men having sex with men
      (MSM) activity. Median age at the time of diagnosis was 48 years (range 20-63).
      Eighty-nine percent received highly active antiretroviral therapy (HAART). Sixty
      seven percent were adherent as defined by a combination of adherence to
      appointments and to treatment. Ninety-seven percent of adherent and 17% non
      adherent patients on HAART had HIV-RNA less than 200 copies per ml (RR=24.2,
      p<0.0001). Poor adherence was associated with younger age (<50 years) (adjusted
      RR=7.95, p=0.005) and living in remote areas with no direct contact with skilled
      personnel (adjusted RR=6.75, p=0.01). Unsafe sex was also more frequent among non
      adherent patients (RR=4.12, p=0.026), but due to few answers this topic was not
      included in the multivariate model. CONCLUSION: The HIV population in Greenland
      is peculiar since most patients are heterosexually infected and middle-aged at
      diagnosis. A relatively poor adherence and consequently inferior treatment
      outcome is related to young age and living in remote areas.

PMID- 22663940
TI  - Assessment of consumption of marine food in Greenland by a food frequency
      questionnaire and biomarkers.
AB  - OBJECTIVES: We studied the association and agreement between questionnaire data
      and biomarkers of marine food among Greenland Inuit. DESIGN: Cross sectional
      study. METHODS: The study population comprised 2,224 Inuit, age 18+ (43% men);
      data collected 2005-2008 in Greenland. Using a food frequency questionnaire
      (FFQ), we calculated consumption of seal, whale, and fish (g/day) and as
      meals/month, intake of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA),
      total N3, and mercury. We measured erythrocyte membrane fatty acids (FA) and
      whole blood mercury (Hg). Associations were assessed by Pearson correlation and
      agreement between the 2 methods was assessed by Bland-Altman plots depicting mean
      difference between the methods. Using multiple linear regressions, the
      associations were studied between whole blood mercury, erythrocyte FA and
      frequency or gram per day of seal, whale, and fish. RESULTS: Partial correlations
      ranged from r=0.16, p<0.0001 (DHA) to r=0.56, p<0.0001 (mercury). The best fitted
      lines were found for mercury and DHA. Mean difference was negative for mercury
      but positive for all the FA biomarkers. In a multiple logistic regression
      analysis, the best association was found between whole blood mercury and seal
      consumption, both as frequency in meals and actual intake gram per day: beta=1.07
      ug (95% CI: 1.06; 1.08) and beta=1.04 ug (95% CI: 1.03; 1.04), respectively.
      CONCLUSION: Mercury showed the best correlation and agreement between calculated
      and measured values. Calculated actual intake in gram per day and frequency of
      meals showed similar associations with whole blood mercury and erythrocyte
      membrane FAs.

PMID- 22663941
TI  - Incidence of pancreatic cancer in Greenland 2000-2010.
AB  - BACKGROUND: Inuit people are known to be at an increased risk of cancers usually
      uncommon to the western world such as cancers of the nasopharynx and salivary
      glands. But what is the trend regarding pancreatic cancer? OBJECTIVE: To
      determine the incidence of pancreatic cancer (PC) in Greenland compared with
      Denmark in the period 2000-2010. STUDY DESIGN: Retrospective register-based
      study. Cases were retrieved from The Danish Cancer Register and The Greenlandic
      Patient Register and stratified in 5-year age intervals for each year. Age
      standardized incidence ratios (SIR) for each year for Greenland compared with
      Denmark were calculated using the number of cases and the number of inhabitants
      in each 5-year age interval and in each country. The average SIR for the entire
      period was calculated using a weighted average. RESULTS: The study revealed a SIR
      of 2.38 (95% CI: 1.97-2.86; p<0.0001) indicating a significantly increased
      incidence of PC in Greenland compared with Denmark. A linear regression analysis
      showed no significant change in the SIR over time (p for trend 0.25) as well as
      no significant change isolated in Greenland (p for trend 0.8). Furthermore, the
      Inuit were significantly younger at the time of diagnosis (mean 62.7 vs. 70.0;
      p<0.0001). CONCLUSIONS: The age-standardized incidence of PC is 138% higher in
      Greenland than in Denmark. A part of this could be explained by a higher
      prevalence of smoking and DM-2. However, the impact of genetic factors cannot be
      disregarded and should be subjected to further investigation.

PMID- 22663942
TI  - Alaska native people's perceptions, understandings, and expectations for research
      involving biological specimens.
AB  - OBJECTIVES: Members of racially and ethnically diverse groups have been
      persistently underrepresented in biomedical research in general, possibly due to
      mistrust with the medical and research community. This article describes the
      perceptions, understandings, and expectations of Alaska Native people about
      research involving the collection and storage of biological specimens. STUDY
      DESIGN: Stratified focus groups. METHODS: Twenty-nine focus groups with Alaska
      Native people (n = 178) were held in 14 locations using a semi-structured
      moderator guide. ATLAS.ti was used for thematic analysis through iterative
      readings and coding. Alaska Native peoples' perceptions, understandings, and
      expectations of researcher beneficence, informed consent processes, and provision
      of research findings were elicited. RESULTS AND CONCLUSIONS: Alaska Native people
      desired extensive disclosure of information beyond that typically provided in
      consent and results dissemination processes. Information germane to the
      motivation and intent of researchers and specifics of specimen storage and
      destruction were specifically requested. A clear and extensive process of
      informed consent and continued improvements in sharing results may enhance the
      transparency of research intent, conduct, and use of obtained results among
      Alaska Native people. Meeting expectations may improve relationships between
      researchers and the Alaska Native population which could result in increased
      research participation. Our findings offer a guide for researchers and
      communities when planning and implementing research with biological specimens.

PMID- 22663943
TI  - Modern contact investigation methods for enhancing tuberculosis control in
      aboriginal communities.
AB  - The Aboriginal communities in Canada are challenged by a disproportionate burden
      of TB infection and disease. Contact investigation (CI) guidelines exist but
      these strategies do not take into account the unique social structure of
      different populations. Because of the limitations of traditional CI, new
      approaches are under investigation and include the use of social network
      analysis, geographic information systems and genomics, in addition to the
      widespread use of genotyping to better understand TB transmission. Guidelines for
      the routine use of network methods and other novel methodologies for TB CI and
      outbreak investigation do not exist despite the gathering evidence that these
      approaches can positively impact TB control efforts, even in Aboriginal
      communities. The feasibility and efficacy of these novel approaches to CI in
      Aboriginal communities requires further investigation. The successful integration
      of these novel methodologies will require community involvement, capacity
      building and ongoing support at every level. The outcome will not only be the
      systematic collection, analysis, and interpretation of CI data in high-burden
      communities to assess transmission but the prioritization of contacts who are
      candidates for treatment of LTBI which will break the cycle of transmission.
      Ultimately, the measure of success will be a clear and sustained decline in TB
      incidence in Aboriginal communities.

PMID- 22663944
TI  - Vertebral artery dominance, brainstem auditory evoked potential, and vertigo of
      vascular origin.
AB  - OBJECTIVE: Vertebral artery dominance (VAD) is defined when there is a
      significant difference between the diameters of the vertebral arteries (VAs). VAD
      may be a risk factor for vertigo of vascular origin. The objectives of this study
      were: (1) to investigate changes of brainstem auditory evoked potential (BAEP) in
      patients with vertigo caused by VAD through magnetic resonance; and (2) to
      understand the possible mechanism(s) by which VAD triggers vertigo of vascular
      origin. METHODS: This prospective study involved 64 patients with vertigo,
      including 35 patients with VAD (VAD group) and 29 without VAD (non-VAD group) as
      detected by head magnetic resonance angiography. Age, sex, and other clinical
      histories were comparable in both groups. The degree of vertigo was graded and
      BAEP examination was performed in each patient. BAEP changes as well as their
      correlations of BAEP with the dominant VA and basilar artery (BA) were analyzed
      in both groups. RESULTS: The rate of abnormal BA shapes was 60% in the VAD group
      compared with 34.5% in the non-VAD group (Chi-square = 4.135, P<0.05). The median
      BA curvature was higher in the VAD group than that in the non-VAD group, 3.67 and
      1.73 mm, respectively (P<0.01). Peak latencies (I, III, and V) in the VAD group
      were longer than those in the non-VAD group (P<0.01), but the difference in the
      III did not reach statistical significance (t = 1.916, P>0.05). Interpeak
      latencies (III-V and I-V) were longer in the VAD group than those in the non-VAD
      group (P<0.05); there was no significant difference in the interpeak latencies of
      I-III (P>0.05). The III-V/I-III ratios were higher in the VAD group than those in
      the non-VAD group. The vertigo severity level was significantly higher in the VAD
      group than that in the non-VAD group (3.2 +/- 1.0 versus 2.2 +/- 0.7). The
      vertigo severity level correlated with VAD and every major anomaly index of BAEP;
      its correlations with III-V/I-III were remarkably significant (r = 0.617, P =
      0.013). CONCLUSION: The incidence of abnormal BA shapes and abnormal BAEP, and
      the vertigo severity level were higher in VAD patients. Moreover, VAD was found
      to correlate with abnormal BAEP, suggesting that VAD contributed to vertigo of
      vascular origin.

PMID- 22663945
TI  - Yeast 5 - an expanded reconstruction of the Saccharomyces cerevisiae metabolic
      network.
AB  - BACKGROUND: Efforts to improve the computational reconstruction of the
      Saccharomyces cerevisiae biochemical reaction network and to refine the
      stoichiometrically constrained metabolic models that can be derived from such a
      reconstruction have continued since the first stoichiometrically constrained
      yeast genome scale metabolic model was published in 2003. Continuing this ongoing
      process, we have constructed an update to the Yeast Consensus Reconstruction,
      Yeast 5. The Yeast Consensus Reconstruction is a product of efforts to forge a
      community-based reconstruction emphasizing standards compliance and biochemical
      accuracy via evidence-based selection of reactions. It draws upon models
      published by a variety of independent research groups as well as information
      obtained from biochemical databases and primary literature. RESULTS: Yeast 5
      refines the biochemical reactions included in the reconstruction, particularly
      reactions involved in sphingolipid metabolism; updates gene-reaction annotations;
      and emphasizes the distinction between reconstruction and stoichiometrically
      constrained model. Although it was not a primary goal, this update also improves
      the accuracy of model prediction of viability and auxotrophy phenotypes and
      increases the number of epistatic interactions. This update maintains an emphasis
      on standards compliance, unambiguous metabolite naming, and computer-readable
      annotations available through a structured document format. Additionally, we have
      developed MATLAB scripts to evaluate the model's predictive accuracy and to
      demonstrate basic model applications such as simulating aerobic and anaerobic
      growth. These scripts, which provide an independent tool for evaluating the
      performance of various stoichiometrically constrained yeast metabolic models
      using flux balance analysis, are included as Additional files 1, 2 and 3.
      CONCLUSIONS: Yeast 5 expands and refines the computational reconstruction of
      yeast metabolism and improves the predictive accuracy of a stoichiometrically
      constrained yeast metabolic model. It differs from previous reconstructions and
      models by emphasizing the distinction between the yeast metabolic reconstruction
      and the stoichiometrically constrained model, and makes both available as
      Additional file 4 and Additional file 5 and at http://yeast.sf.net/ as separate
      systems biology markup language (SBML) files. Through this separation, we intend
      to make the modeling process more accessible, explicit, transparent, and
      reproducible.

PMID- 22663948
TI  - Is there a need for safety monitoring guidelines for antidepressant treatment?

PMID- 22663946
TI  - Comparison of brain volume abnormalities between ADHD and conduct disorder in
      adolescence.
AB  - BACKGROUND: Previous studies of brain structure abnormalities in conduct disorder
      and attention-deficit/hyperactivity disorder (ADHD) samples have been limited
      owing to cross-comorbidity, preventing clear understanding of which structural
      brain abnormalities might be specific to or shared by each disorder. To our
      knowledge, this study was the first direct comparison of grey and white matter
      volumes in diagnostically "pure" (i.e., no comorbidities) conduct disorder and
      ADHD samples. METHODS: Groups of adolescents with noncormobid conduct disorder
      and with noncomorbid, combined-subtype ADHD were compared with age- and sex
      matched controls using DARTEL voxel-based analysis of T1-weighted brain structure
      images. Analysis of variance with post hoc analyses compared whole brain grey and
      white matter volumes among the groups. RESULTS: We included 24 adolescents in
      each study group. There was an overall 13% reduction in grey matter volume in
      adolescents with conduct disorder, reflecting numerous frontal, temporal,
      parietal and subcortical deficits. The same grey matter regions typically were
      not abnormal in those with ADHD. Deficits in frontal lobe regions previously
      identified in studies of patients with ADHD either were not detected, or group
      differences from controls were not as strong as those between the conduct
      disorder and control groups. White matter volume measurements did not
      differentiate conduct disorder and ADHD. LIMITATIONS: Our modest sample sizes
      prevented meaningful examination of individual features of ADHD or conduct
      disorder, such as aggression, callousness, or hyperactive versus inattentive
      symptom subtypes. CONCLUSION: The evidence supports theories of frontotemporal
      abnormalities in adolescents with conduct disorder, but raises questions about
      the prominence of frontal lobe and striatal structural abnormalities in those
      with noncomorbid, combined-subtype ADHD. The latter point is clinically
      important, given the widely held belief that ADHD is associated with numerous
      frontal lobe structural deficits, a conclusion that is not strongly supported
      following direct comparison of diagnostically pure groups. The results are
      important for future etiological studies, particularly those seeking to identify
      how early expression of specific brain structure abnormalities could potentiate
      the risk for antisocial behaviour.

PMID- 22663949
TI  - A multicenter evaluation of the safety of drotrecogin alfa (activated) in
      patients with baseline bleeding precautions.
AB  - PURPOSE: We recently reported an increased incidence of serious bleeding events
      and mortality in patients with baseline bleeding precautions treated with
      drotrecogin alfa (activated) compared to patients without such precautions.
      Whether these observations were specific to our single medical campus is unclear.
      METHODS: All patients who received drotrecogin alfa (activated) for the treatment
      of severe sepsis from January 2006 through September 2009 within the South
      Central Veterans Affairs Health Care Network were retrospectively reviewed using
      a regional clinical database. Demographic information, bleeding precautions that
      were exclusion criteria of the PROWESS trial, and 30-day post-discharge
      incidences of serious bleeding events and mortality were collected. RESULTS:
      Seventy-nine patients from 5 medical centers were included. Serious bleeding
      events occurred in 4 of 24 patients (16.7%) with any bleeding precaution vs 1 of
      55 patients (1.8%) without a bleeding precaution (P=0.03). All patients (5) who
      experienced a serious bleeding event died compared to 39 of 74 patients (52.7%)
      who did not (P=0.06). Seventeen of 24 patients (70.8%) with bleeding precautions
      died vs 27 of 55 patients (49.1%) without bleeding precautions (P=0.07). The
      number of serious bleeding events did not allow meaningful multivariate analyses.
      The mean number of failing organs was an independent predictor of 30-day post
      discharge mortality (OR 1.63 for each organ failed, 95% CI 1.05- 2.6).
      CONCLUSIONS: The findings of this study were consistent with our prior
      observations and suggest the risk for serious bleeding events with drotrecogin
      alfa (activated) may outweigh any potential benefit in patients with baseline
      bleeding precautions.

PMID- 22663947
TI  - Inhibition of the cortex using transcranial magnetic stimulation in psychiatric
      populations: current and future directions.
AB  - Several lines of evidence suggest that deficits in gamma-aminobutyric acid (GABA)
      inhibitory neurotransmission are implicated in the pathophysiology of
      schizophrenia, bipolar disorder, major depressive disorder and obsessive
      compulsive disorder. Cortical inhibition refers to a neurophysiological process,
      whereby GABA inhibitory interneurons selectively attenuate pyramidal neurons.
      Transcranial magnetic stimulation (TMS) represents a noninvasive technique to
      measure cortical inhibition, excitability and plasticity in the cortex. These
      measures were traditionally specific to the motor cortex, which is an important
      limitation when nonmotor neurophysiological processes are of primary interest.
      Recently, TMS has been combined with electro encephalography (EEG) to derive such
      measurements directly from the cortex. This review focuses on neurophysiological
      studies related to inhibitory and excitatory TMS paradigms, linking dysfunctional
      GABAergic neurotransmission to disease states. We review evidence that suggests
      cortical inhibition deficits among psychiatric populations and demonstrate how
      each disorder has a specific neurophysiological response to treatment. We
      conclude by discussing the future directions of TMS combined with EEG,
      demonstrating the potential to identify biological markers of neuropsychiatric
      disorders.

PMID- 22663950
TI  - Irritable bowel syndrome and drospirenone-containing oral contraceptives; a
      comparative-safety study.
AB  - BACKGROUND: Mineralocorticoids are thought to play a role in tissue repair,
      including fibrous tissue formation. The antimineralocorticoid activity of
      spironolactone has been linked to an increased risk of gastrointestinal bleeding.
      Drospirenone is a synthetic progestin approved in combination with ethinyl
      estradiol as an oral contraceptive (OC). It is a spironolactone-derivative, and
      its antimineralocorticoid effects could irritate the gastrointestinal tract
      leading to symptoms of irritable bowel syndrome (IBS). METHODS: A retrospective
      cohort study was conducted evaluating women 18-46 years of age in the IMS claims
      database. New-users of progestin-based OCs were identified between 1997-2009.
      Ninety days of OC therapy and one year of prior enrollment with no prior
      diagnosis of IBS were required for inclusion. Cases were identified using a
      previously validated method for the diagnosis of IBS. Cox proportional hazards
      models were used to estimate the hazard ratio (HR) for developing IBS with the
      different OC formulations using levonorgestrel as a reference. RESULTS: The
      cohort included 939,281 women, averaging 29.1 years of age and 247 days of OC
      therapy. 3,050 incident cases of IBS were detected. The annualized incidence for
      IBS with drospirenone was 0.77% (1083 cases) while that for levonorgestrel was
      0.46% (483 cases). The crude HR for development of IBS with drospirenone compared
      to levonorgestrel was 1.70 (95%CI 1.53-1.90), while the adjusted HR was 1.63
      (95%CI 1.46-1.82). Multiple sensitivity analyses confirmed this association.
      Other OCs were unassociated with IBS. CONCLUSION: Our study found a positive
      association between drospirenone and a diagnosis of IBS that was not observed
      with other OCs.

PMID- 22663951
TI  - Analgesic drug use associated with statin prescription--a cross-sectional study
      in primary care settings.
AB  - BACKGROUND: To investigate whether features of muscular complaints (MC) differ
      between receivers of a statin prescription and non-receivers. To analyze the
      relationship between analgesics prescription, statin prescription and/or
      musculoskeletal disorders. METHODS: Cross-sectional study. Consecutive patients
      in offices of family practitioners were interviewed using a standardized
      questionnaire. Target variables: Rates of features of MC in patients with or
      without a statin prescription and rates of analgesic drug prescription in
      patients with or without statin prescription and/or musculoskeletal disorders.
      Odds ratios (adjusted for age, sex, and socio-economic status) were calculated
      using logistic regression analysis. RESULTS: 1135 patients in 26 general
      practitioners' offices were asked to participate, and 1031 patients agreed.
      Features of MC did not differ between the two groups of patients. Analgesic
      prescription was found to be associated with statin prescription in patients
      without musculoskeletal disorders (OR 2.2, CI 1.1-4.7 without statin, OR 2.5, CI
      0.9-6.9 with statin) and particularly in those with musculoskeletal disorders (OR
      5.2, CI 2.9-9.3 without statin, OR 9.3, CI 4.5-19.1 with statin). CONCLUSIONS:
      Analgesic prescriptions are probably positively associated with statin
      prescription. Assuming that analgesics attenuate MC, an even stronger association
      between MC and statin use seems likely. The results generate the hypothesis that
      statin use contributes to analgesic use in primary care patients.

PMID- 22663952
TI  - Atypical presentation of tardive dyskinesia associated with risperidone long
      acting injection as maintenance treatment in bipolar affective disorder: a case
      report.
AB  - Second-generation antipsychotics have been growingly implicated in the acute and
      maintenance treatment for bipolar affective disorder (BAD). Risperidone long
      acting injection (LAI) has been the first second-generation depot indicated for
      its maintenance treatment. However, its long-term motor side-effects, especially
      tardive dyskinesia (TD), has not been commonly reported or studied. The case
      reported here a bipolar patient with atypical presentation of TD involving only
      the crico-hyoid region of the neck associated with the use of risperidone LAI in
      adjunct to lithium and sodium valproate as maintenance therapy.

PMID- 22663953
TI  - Severe neutropenia in a renal transplant patient suggesting an interaction
      between mycophenolate and fenofibrate.
AB  - OBJECTIVE: To describe a patient in whom initiation of micronized fenofibrate
      precipitated mycophenolate induced neutropenia. CASE SUMMARY: A 57-year-old man
      was admitted to the hospital because of febrile neutropenia. He had undergone
      kidney transplantation seventeen years ago. The patient's immunosuppressive
      maintenance regimen consisted of mycophenolate mofetil (MMF) 500 mg three times a
      day, and meprednisone 4 mg daily. His medical history included, hypertension
      treated with losartan 50mg daily, and dyslipidemia treated with ezetimibe 10mg
      /simvastatin 20mg for four years (until 2 weeks before admission when micronized
      fenofibrate 200 mg per day was started because of persistently elevated
      triglycerides levels. On presentation temperature was 37.8 degrees C and initial
      laboratory tests showed 3130 White Blood Cell Count(WBC)/MUL with neutropenia
      (absolute neutrophil count (ANC) 313/MUL) Fenofibrate and mycophenolate mofetil
      were discontinued, piperacillin tazobactam 4.5gr three times a day and
      granulocyte stimulation factor 300 MUg/day were started. Three days after
      admission WBC was 7280/MUL, neutrophils: 22%, ANC: 1160/mm(3). Mycophenolate
      mofetil was restarted and granulocyte stimulation factor was discontinued. One
      month after discharge his WBC was 4480/MUL and ANC 1926/MUL. DISCUSSION: The
      initiation of fenofibrate in a patient on stable and therapeutic doses of
      mycophenolate may have precipitated mycophenolate induced neutropenia, a well
      described, dose dependent phenomenon. Mycophenolic acid (MPA) displays a complex
      pharmacokinetic profile susceptible to potential significant interactions with
      fenofibrate. Since approximately 99% of MPA and fenofibrate bind to albumin,
      displacement may occur, leading to increased free MPA. Second competition of
      fenofibric acid for UGT1A9 an enzyme implicated in conjugation of MPA may have
      decreased its metabolism. The combination of these two effects may increase the
      risk of dose dependent neutropenia. Using the Interaction Probability Scale
      (DIPS), the interaction was designated as probable. CONCLUSIONS: Until further
      evidence is available, when fenofibrate is started in a renal transplant patient
      on mycophenolate careful monitoring should be considered to avoid potentially
      fatal complications.

PMID- 22663954
TI  - A fatal outcome after unintentional overdosing of rivastigmine patches.
AB  - BACKGROUND: Rivastigmine is an acetylcholine esterase inhibitor used in the
      treatment of dementia. Patches with rivastigmine for transdermal delivery have
      been used to increase compliance and to reduce side effects. CASE REPORT: We
      describe an 87-year old male with dementia treated with multiple rivastigmine
      patches (Exelon 9,5 mg/24 h) who developed nausea, vomiting and renal failure
      with disturbed electrolytes resulting in death. The symptoms occurred after six
      rivastigmine patches had concomitantly been erroneously applied by health care
      personnel on two consecutive days. The terminal cause of death was considered to
      be uremia from an acute tubular necrosis that was assessed as a result of
      dehydration through vomiting. The rivastigmine intoxication was assessed as
      having caused or contributed to the dehydrated condition. The medication error
      occurred at least partly due to ambiguous labeling. The clinical signs were not
      initially recognized as adverse effects of rivastigmine. DISCUSSION: The
      presented case is a description of a rivastigmine overdose due to a medication
      error involving patches. This case indicates the importance of clear and
      unambiguous instructions to avoid administration errors with patches and to be
      vigilant to adverse drug reactions for early detection and correction of drug
      administration errors. In particular, instructions clearly indicating that only
      one patch should be applied at a time are important.

PMID- 22663955
TI  - Statin related memory dysfunction in a Nigerian woman: a case report.
AB  - Statins are useful in the treatment of dyslipidemia commonly associated with
      hypertension and diabetes mellitus. They are not devoid of side effects chief of
      which are musculo-skeletal.Memory impairment as a side effect is not common; and
      has not been reported in Nigeria to author's knowledge. This case report is on a
      woman who with Simvastatin developed memory deficits which adversely affected
      activities of daily living. Clinicians are enjoined to be on the alert for this,
      and should respond appropriately when it arises.

PMID- 22663956
TI  - Central anti-cholinergic syndrome induced by single therapeutic dose of atropine.
AB  - A 55 years old male patient, who is planned for bronchoscopy developed central
      anti-cholinergic syndrome due to therapeutic dose of atropine. Withdrawal of
      atropine has improved the symptoms. Thereafter, instillation of atropine as eye
      drops leads to reappearance of symptoms. The reaction was definite according to
      Naranjo's algorithm. It was severe and definitely preventable according to
      Modified Hartwig and Siegel's scale and Modified Schumock and Thornton scale
      respectively. Central anti-cholinergic syndrome may be due to variation in the
      genetic susceptibility (Idiosyncrasy) to atropine. Idiosyncratic reaction on
      administration of atropine as a pre-anesthetic medication or eye drops should be
      kept in mind while prescribing.

PMID- 22663957
TI  - 3D in vitro technology for drug discovery.
AB  - Three-dimensional (3D) in vitro systems that can mimic organ and tissue structure
      and function in vivo, will be of great benefit for a variety of biological
      applications from basic biology to toxicity testing and drug discovery. There
      have been several attempts to generate 3D tissue models but most of these models
      require costly equipment, and the most serious disadvantage in them is that they
      are too far from the mature human organs in vivo. Because of these problems,
      research and development in drug discovery, toxicity testing and biotech
      industries are highly expensive, and involve sacrifice of countless animals and
      it takes several years to bring a single drug/product to the market or to find
      the toxicity or otherwise of chemical entities. Our group has been actively
      working on several alternative models by merging biomaterials science,
      nanotechnology and biological principles to generate 3D in vitro living organs,
      to be called "Human Organs-on-Chip", to mimic natural organ/tissues, in order to
      reduce animal testing and clinical trials. We have fabricated a novel type of
      mechanically and biologically bio-mimicking collagen-based hydrogel that would
      provide for interconnected mini-wells in which 3D cell/organ culture of human
      samples in a manner similar to human organs with extracellular matrix (ECM)
      molecules would be possible. These products mimic the physical, chemical, and
      biological properties of natural organs and tissues at different scales. This
      paper will review the outcome of our several experiments so far in this direction
      and the future perspectives.

PMID- 22663958
TI  - The frequency of thrombotic events among adults given antifibrinolytic drugs for
      spontaneous bleeding: systematic review and meta-analysis of observational
      studies and randomized trials.
AB  - AIMS: The antifibrinolytic drug tranexamic acid (TXA) improves survival after
      trauma. Antifibrinolytic drugs may also improve outcome after spontaneous
      bleeding, so we conducted a systematic review of the frequency of thrombotic
      events associated with their use after spontaneous bleeding, to help design
      future randomized controlled trials. METHODS: We sought trials or observational
      studies of >=20 adults involving any antifibrinolytic drug (TXA,
      epsilonaminocaproic acid (EACA) or aprotinin) for spontaneous (non-traumatic, non
      surgical/iatrogenic), non-heamophiliac bleeding. We searched the Cochrane Central
      Register of Controlled Trials, OVID Medline from 1966, EMBASE from 1980, and the
      bibliographies of relevant articles in October 2009. We meta-analysed proportions
      of patients with thrombotic events, using a random effects model. RESULTS: We
      found 57 studies involving 5,049 patients, 3,616 (72%) of whom had spontaneous
      subarachnoid haemorrhage. 3,414 (68%) patients received TXA-based treatment and
      1,635 (32%) received EACA. The frequencies of limb ischaemia and myocardial
      infarction were <1% for TXA and EACA. The frequency of deep vein thrombosis or
      pulmonary embolism was 1.9% (95% confidence interval (CI) 1.1 to 2.9) for TXA and
      3.0% (95% CI 1.8 to 4.6) for EACA. The occurrence of cerebral infarction was
      restricted to studies of subarachnoid haemorrhage when compared to other
      indications, both for TXA (9.7% [95% CI 5.5 to 14.8] versus 0% [95% CI 0 to 0.5])
      and for EACA (7.7% [95% CI 1.8 to 17.4] versus 0% [95% CI 0 to 2.1]).
      CONCLUSIONS: Thrombotic events have occurred infrequently with antifibrinolytic
      drugs after spontaneous bleeding apart from subarachnoid haemorrhage, so further
      exploration of their safety and efficacy after spontaneous bleeding is justified
      in randomized trials.

PMID- 22663959
TI  - Update on the adverse effects of clozapine: focus on myocarditis.
AB  - Clozapine, an atypical antipsychotic, is a dibenzodiazepine derivative and its
      therapeutic effects are probably mediated by dopaminergic and serotonergic
      activity. In accordance to several studies, it appears to be the most effective
      antipsychotic drug for treatment-resistant schizophrenia. Moreover, clozapine
      appears to be particularly beneficial in patients with schizophrenia who are
      suicidal and in those with comorbid substance use disorder. However, despite its
      efficacy, the general use of clozapine in clinical practice is somewhat limited
      because of the risk of several serious adverse effects such as agranulocytosis
      and thromboembolism. Clozapine may be associated with fatal myocarditis and
      cardiomyopathy in physically healthy young adults. Consequently, the FDA and the
      drug's manufacturer have strengthened warnings to include that a potentially
      fatal myocarditis may occur when taking clozapine. In the present paper the
      literature on clozapine-related myocardis will be reviewed and practical advice
      will be given concerning the diagnosis and management of such potentially fatal
      adverse effect.

PMID- 22663960
TI  - Impulsive and compulsive behaviors during dopamine replacement treatment in
      Parkinson's Disease and other disorders.
AB  - Impulsive and compulsive behaviors, including pathologic gambling,
      hypersexuality, compulsive shopping, compulsive eating, excessive engagement in
      hobbies, punding, and Dopamine Dysregulation Syndrome (DDS), are increasingly
      reported serious side-effects of dopaminergic medication, used in the treatment
      of Parkinson's Disease (PD) and other disorders. Dopamine Agonists (DA) are
      strongly related with Impulse Control Disorders (ICDs), while L-dopa is
      associated with DDS. The present paper focuses on ICDs. The estimated prevalence
      of ICDs in PD patients treated with DA is as high as 14%. ICDs pathophysiology is
      complex, due to multiple contributing factors. Dopamine neurotransmission along
      the meso-cortico-limbic pathway is a modulator of risk behavior and can be
      altered in PD and in the course of dopaminergic treatment. Psychiatric
      complications, associated with treatment of PD are still underdiagnosed, although
      their consequences can be serious, even catastrophic. Physicians treating PD with
      DA should warn the patients and their relatives of the risk of inducing ICDs.
      Psychiatrists should be trained to recognize these side effects, that can mimic
      primary psychiatric conditions. The management of ICDs includes discontinuation
      of DA or switching from DA to other drugs for the treatment of PD. Cognitive
      behavior therapy, serotonin selective reuptake inhibitors, nalmefene, zonisamide,
      low dose of anti-dopaminergic drugs, as quetiapine or clozapine, can be
      effective. Psychological, spiritual, and ethical support (familial or individual)
      can help.

PMID- 22663961
TI  - Safety and efficacy of aliskiren in the treatment of hypertension and associated
      clinical conditions.
AB  - Aliskiren is the first known representative of a new class of non-peptide orally
      active renin inhibitors that blocks the renin-angiotensin-aldosterone-system
      (RAAS) at its rate-limiting step. It induces a net reduction in plasma renin
      activity (PRA), angiotensin II and aldosterone levels. Aliskiren is effective in
      reducing blood pressure (BP) and is well tolerated. The incidence of adverse
      events and the number of study discontinuations as a result of adverse events
      during aliskiren treatment were relatively low and generally not dissimilar from
      placebo. In placebo-controlled studies, aliskiren showed a dose-related
      systolic/diastolic BP lowering effect at doses between 75 and 300 mg/day. When
      compared to active treatments, aliskiren was generally as effective as
      hydrochlorothiazide, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin
      receptor blockers (ARBs) and beta-blockers, in reducing BP. Aliskiren exhibits
      synergistic effects when combined with drugs that lead to a reactive increase in
      the PRA, such as diuretics, ACE inhibitors or ARBs. Although in clinical studies
      aliskiren proved to reduce proteinuria, the early termination of the Aliskiren
      Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints
      (ALTITUDE) confirms previous concerns about the full suppression of the RAAS, in
      this case with aliskiren combined with ACE-inhibitors or ARBs, in patients with
      diabetes and concomitant renal impairment. This review summarizes the available
      data on its safety profile and its clinical development for treatment of arterial
      hypertension, diabetes and nephropathy.

PMID- 22663962
TI  - Definitions and epidemiology of the chronically critically ill.
AB  - Patients who are chronically critically ill constitute 5-10% of patients with
      acute respiratory failure but demand a disproportionate share of ICU resources.
      Epidemiologic studies and clinical trials require definitions for enrollment, and
      a uniform definition would be ideal  to allow comparisons between studies. While
      a consensus definition exists (>= 21 consecutive days of mechanical ventilation
      for >= 6 h/d), many study designs have required alternative definitions that
      include requirement for a tracheostomy, a different period of mechanical
      ventilation,  or admission to a weaning facility. Regardless of definition,
      studies have indicated that the incidence of chronic critical illness has doubled
      in recent decades and may double again in the next decade. The overall 1-year
      survival for chronically critically ill patients is between 40% and  50%,
      depending on the cohort studied. New clinical prediction rules have been
      developed to better identify patients who are at high risk and low risk of death.
      These models could be enhanced by data on functional outcomes for survivors. The
      healthcare system has been adapting to the increase  in chronic critical illness
      by increasing critical beds in short-term and long-term acute care hospitals, but
      continued monitoring of resources will be necessary, since the prevalence of
      chronic critical illness is expected to increase further.

PMID- 22663963
TI  - Persistent systemic inflammation in chronic critical illness.
AB  - Chronic critical illness (CCI) is syndrome of neuromuscular weakness, brain
      dysfunction, malnutrition, endocrinopathies, and symptom distress. Two conceptual
      themes may be useful in discussing CCI. The first is a clinical roadmap in which
      a patient suffers an acute critical illness,  survives the initial insult, but
      yet is unable to be liberated from the ventilator. The second framework considers
      the effect of systemic inflammation and CCI, linking acute CCI risk factors with
      the common clinical features of CCI. Given the association between common CCI
      antecedents and  inflammation, attempts to control and balance the pro
      inflammatory and anti-inflammatory mediators should begin as early as possible
      and continue throughout the ICU stay. Since surrogate measures such as biomarkers
      often fail to predict the effect of interventions, the focus should be on the 
      outcomes patients experience. As of now, providing evidence-based, high quality
      ICU management of patients at risk for CCI appears to be the best strategy of
      care.

PMID- 22663964
TI  - Current venues of care and related costs for the chronically critically ill.
AB  - The chronically critically ill (CCI) patient population is characterized by a
      prolonged need for high cost medical interventions, a high 1-year mortality rate,
      and a very high demand for post acute care services. The best characterized CCI
      patient population is patients on prolonged  mechanical ventilation (PMV). This
      review will focus on the current knowledge of costs and care venues for the care
      of this patient population. The PMV population suffers from a prolonged length of
      acute care hospital stay, median hospital costs 3-4 times the cost of short-term
      ventilator  patients, frequent care venue changes during the course of illness, a
      small likelihood of discharge to the home environment, yet a hospital mortality
      that does not differ significantly from the short-term ventilated patient group.
      The PMV population is projected to double in size by the year  2020. Given the
      dramatic comparative acute care cost burden of PMV patients, the societal
      implications for managing both the care burden and the costs of care are
      staggering. Strategies to improve the efficiency in healthcare for this patient
      population will be essential. Limitations to the  existing care models in the
      United States will be identified with a focus on our current research
      deficiencies, which limit healthcare providers and administrators in providing
      patient focused care for this patient population.

PMID- 22663965
TI  - Long-term mechanical ventilation: management strategies.
AB  - This paper reviews management strategies for patients undergoing prolonged
      mechanical ventilation (PMV). Topics covered include how to identify and correct
      barriers to weaning, the systematic approach to weaning trials, when to cease
      weaning trials and proceed with life-long support,  managing the tracheostomy
      tube during PMV, and, finally, how to select a suitable mechanical ventilator for
      PMV.

PMID- 22663966
TI  - The growing role of noninvasive ventilation in patients requiring prolonged
      mechanical ventilation.
AB  - For many patients with chronic respiratory failure requiring ventilator support,
      noninvasive ventilation (NIV) is preferable to invasive support by tracheostomy.
      Currently available evidence does not support the use of nocturnal NIV in
      unselected patients with stable COPD. Several European  studies have reported
      benefit for high intensity NIV, in which setting of inspiratory pressure and
      respiratory rate are selected to achieve normocapnia. There have also been
      studies reporting benefit for the use of NIV as an adjunct to exercise training.
      NIV may be useful as an adjunct to  airway clearance techniques in patients with
      cystic fibrosis. Accumulating evidence supports the use of NIV in patients with
      obesity hypoventilation syndrome. There is considerable observational evidence
      supporting the use of NIV in patients with chronic respiratory failure related to
      neuromuscular  disease, and one randomized controlled trial reported that the use
      of NIV was life-prolonging in patients with amyotrophic lateral sclerosis. A
      variety of interfaces can be used to provide NIV in patients with stable chronic
      respiratory failure. The mouthpiece is an interface that is unique  in this
      patient population, and has been used with success in patients with neuromuscular
      disease. Bi-level pressure ventilators are commonly used for NIV, although there
      are now a new generation of intermediate ventilators that are portable, have a
      long battery life, and can be used for NIV  and invasive applications. Pressure
      support ventilation, pressure controlled ventilation, and volume controlled
      ventilation have been used successfully for chronic applications of NIV. New
      modes have recently become available, but their benefits await evidence to
      support their widespread use.  The success of NIV in a given patient population
      depends on selection of an appropriate patient, selection of an appropriate
      interface, selection of an appropriate ventilator and ventilator settings, the
      skills of the clinician, the motivation of the patient, and the support of the
      family.

PMID- 22663967
TI  - Long-term home mechanical ventilation in the United States.
AB  - Patients requiring prolonged mechanical ventilation are rapidly increasing in
      number. Improved ICU care has resulted in many patients surviving acute
      respiratory failure to require prolonged mechanical ventilation during
      convalescence. Also, mechanical ventilation is increasingly used  as a
      therapeutic option for patients with symptomatic chronic hypoventilation, with an
      increased effort to predict nocturnal hypoventilation to initiate ventilation
      earlier. There are continued efforts by ventilator manufacturers to improve home
      ventilators. These factors point to a likely  increase in the number of patients
      receiving home mechanical ventilation in the United States. Unfortunately, there
      are no comprehensive databases or national registry of home ventilator patients
      therefore the number of home ventilator patients is unknown. There are real
      challenges to  providing mechanical ventilation in the home, which include
      caregiver training, adequacy of respiratory care, and reimbursement.

PMID- 22663968
TI  - Critical illness neuromyopathy and the role of physical therapy and
      rehabilitation in critically ill patients.
AB  - Neuromuscular complications of critical illness are common, and can be severe and
      persistent, with substantial impairment in physical function and long-term
      quality of life. While the etiology of ICU-acquired weakness (ICUAW) is
      multifactorial, both direct (ie, critical illness neuromyopathy)  and indirect
      (ie, immobility/disuse atrophy) complications of critical illness contribute to
      it. ICUAW is often difficult to diagnose clinically during the acute phase of
      critical illness, due to the frequent use of deep sedation, encephalopathy, and
      delirium, which impair physical examination  for patient strength. Despite its
      limitations, physical examination is the starting point for identification of
      ICUAW in the cooperative patient. Given the relative cost, invasiveness, and need
      for expertise, electrophysiological testing and/or muscle biopsy may be reserved
      for weak patients  with slower than expected improvement on serial clinical
      examination. Currently there are limited interventions to prevent or treat ICUAW,
      with tight glycemic control having the greatest supporting evidence. There is a
      paucity of clinical trials evaluating the specific role of early rehabilitation 
      in the chronic critically ill. However, a number of studies support the benefit
      of intensive rehabilitation in patients receiving chronic mechanical ventilation.
      Furthermore, emerging data demonstrate the safety, feasibility, and potential
      benefit of early mobility in critically ill patients,  with the need for
      multicenter randomized trials to evaluate potential short- and long-term benefits
      of early mobility, including the potential to prevent the need for prolonged
      mechanical ventilation and/or the development of chronic critical illness, and
      other novel treatments on patients'  muscle strength, physical function, quality
      of life, and resource utilization. Finally, the barriers, feasibility, and
      efficacy of early mobility in both medical and other ICUs (eg, surgical,
      neurological, pediatric), as well as in the chronic critically ill, have not been
      formally evaluated  and require exploration in future clinical trials.

PMID- 22663969
TI  - Brain dysfunction in patients with chronic critical illness.
AB  - Critically ill patients frequently experience acute brain dysfunction in the form
      of coma or delirium, both of which are common during acute and chronic critical
      illness (CCI). These manifestations of brain dysfunction are associated with
      numerous adverse outcomes during acute critical  illness, including prolonged
      hospitalization, increased healthcare costs, and increased mortality. The
      prognosis of CCI patients with coma or delirium has not yet been thoroughly
      studied, but preliminary studies suggest this population is at high risk for
      detrimental outcomes associated with  acute brain dysfunction. Additionally, a
      high percentage of patients who survive acute or CCI suffer from long-term brain
      dysfunction, which manifests primarily as memory deficits and executive
      dysfunction and is predicted by brain dysfunction in the ICU. Interventions
      directed at reducing  the burden of brain dysfunction during critical illness
      have shown promise in studies of patients with acute critical illness, but these
      therapies have yet to be studied during CCI. Thus, multicenter randomized trials
      are needed to determine which interventions are most effective for such 
      patients. Until these data are available, management strategies that have been
      proven beneficial during acute critical illness-such as reduction of sedative
      exposure, especially to benzodiazepines, and early use of physical and
      occupational therapy-should be employed during the  treatment of patients with
      CCI.

PMID- 22663970
TI  - Metabolic and nutrition support in the chronic critical illness syndrome.
AB  - Technological innovations in the ICU have led to artificially prolonged life,
      with an associated cost. Chronic critical illness (CCI) occurs in patients with
      prolonged mechanical ventilation and allostatic overload, and is associated with
      a discrete and consistent metabolic syndrome.  Metabolic interventions are
      extrapolated from clinical critical care research, scientific theory, and years
      of CCI patient care experience. Intensive metabolic support (IMS) is a multi
      targeted approach consisting of tight glycemic control with intensive insulin
      therapy, early and adequate  nutrition therapy, nutritional pharmacology,
      management of metabolic bone disease, and meticulous attention to other
      endocrine/metabolic derangements. Ideally, IMS should be under the supervision of
      a metabolic support consultative team. Further research specifically focused on
      the CCI population  is needed to validate this current approach.

PMID- 22663971
TI  - Infections and the compromised immune status in the chronically critically ill
      patient: prevention strategies.
AB  - An estimated 2-3% of all hospitalized patients become critically ill. These
      patients are in a state of relative immune exhaustion, which cripples their
      response to infections. Patients are sicker, have many comorbidities, and undergo
      complex procedures. This clinical picture,  combined with increasing technologies
      and improved survival, presents unique challenges and demands a high level of
      services and expertise over a prolonged period of time. Long-term acute care
      hospitals provide these services, and the migration of chronically critically ill
      patients to these  institutions facilitates defining (and quantifying) the
      spectrum of disease and how to best manage them. The prevalence of multidrug
      resistant organism colonization and infection upon arrival to long-term acute
      care hospitals is high. Admission screening, and appropriate isolation and
      infection  control practices can prevent transmission of these organisms. The
      implementation of ventilator-associated pneumonia prevention protocols, blood
      stream infection prevention protocols, and minimizing Foley urinary catheter use
      can decrease hospital-acquired infection rates and keep them low.  In addition,
      specific attention is required to environmental services and surface and
      equipment cleaning. A well organized infection control program and an
      antimicrobial stewardship program have become indispensable to achieve these
      goals. All of these key principles and recommendations are  also relevant to the
      chronically ill patient in acute care hospital ICUs and step-down units.

PMID- 22663972
TI  - The chronically critically ill patient: pediatric considerations.
AB  - Whether defined as chronically critically ill, long-term mechanical ventilator
      dependent (or otherwise chronically medically supported), or medically fragile, a
      population of infants and children with chronic illness clearly exists. Infants
      and children with chronic healthcare needs  are at an increased risk for
      physical, developmental, behavioral, and/or emotional conditions and generally
      require healthcare services of a type or amount beyond that of a general
      pediatric or adult population. This review will focus on the specific management
      and psychosocial needs associated  with the healthcare of this subgroup of
      infants and children with chronic illness. Attention will be paid to defining the
      population, describing trends over time, reviewing their special needs, and
      discussing outcomes. Increased focus and an increasing quantity of resources for
      this subgroup  of infants and children are needed, as the number of such
      pediatric patients continues to grow.

PMID- 22663974
TI  - Research needs and strategies to establish best practices and cost effective
      models for chronic critical illness.
AB  - Past research in chronic critical illness has been effective in defining the
      population and identifying unique aspects of their outcomes and resource needs,
      but there has been little research focused on interventions to improve outcomes.
      This review discusses some research priorities  that could have immediate impact
      on patient outcomes. General topics include prevention or limiting the incidence
      of chronic critical illness; specific topics related to patient management, such
      as interventions for weaning, rehabilitation, nutrition or infections; and
      methods to enhance communication  and end-of-life care. In addition to specific
      patient management interventions, further comparative effectiveness research on
      care settings is indicated, considering the expected growth in the patient
      population and the substantial resource needs.

PMID- 22663973
TI  - Integration of palliative care in chronic critical illness management.
AB  - Palliative care is an essential component of comprehensive care for all patients
      with chronic critical illness, including those receiving restorative or life
      sustaining therapies. Core elements include alleviation of symptom distress,
      communication about care goals, alignment of treatment  with the patient's values
      and preferences, transitional planning, and family support. Here we address
      strategies for assessment and management of symptoms, including pain, dyspnea,
      and depression, and for assisting patients to communicate while endotracheally
      intubated. We also discuss approaches  to optimize communication among
      clinicians, patients, and families about care goals. Challenges for supporting
      families and planning for transitions between care settings are identified, while
      the value of interdisciplinary input is emphasized. We review "consultative" and
      "integrative"  models for integrating palliative care and restorative critical
      care. Finally, we highlight key ethical issues that arise in the care of
      chronically critically ill patients and their families.

PMID- 22663975
TI  - Chronic critical illness: the growing challenge to health care.
AB  - The chronically critically ill (CCI) comprise a rapidly growing population of
      patients who have survived acute critical illness, only to be left with ongoing
      organ dysfunctions requiring high levels of specialized care for months or years.
      In many ways, CCI is an "iatrogenic"  process, reflecting the ability of modern
      life support technologies to keep patients alive for prolonged periods of time
      despite ongoing life threatening illness. Venues of care for the CCI patient
      include acute care hospitals (both ICU and step-down facilities), specialized
      long term acute  care hospitals, and, less commonly, skilled nursing facilities,
      or even the home. Importantly, CCI patients transition among these venues
      frequently, reflecting the nature of CCI to be punctuated with episodes of acute
      critical illness. Management of the CCI population requires a special combination
      of intensive care and rehabilitative skills.

PMID- 22663976
TI  - Synthesis and characterization of the core-shell magnetic molecularly imprinted
      polymers (Fe3O4@MIPs) adsorbents for effective extraction and determination of
      sulfonamides in the poultry feed.
AB  - In this study, we present a general method to prepare the core-shell magnetic
      molecularly imprinted polymers (MIPs) nanoparticles (NPs) for sulfamethazine
      (SMZ). The resulting Fe3O4@MIPs NPs possess a highly improved imprinting effect,
      fast adsorption kinetics and high adsorption capacity, and can be applied to
      extract sulfonamide in the poultry feed. In this protocol, the magnetite NPs were
      synthesized by co-precipitating Fe2+ and Fe3+ in an ammonia solution first.
      Silica was then coated on the Fe3O4 NPs using a sol-gel method to obtain silica
      shell magnetic NPs. Subsequently, the vinyl groups were grated onto silica
      modified Fe3O4 surface by 3-methacryloyloxypropyltrimethoxysilane. Finally, the
      MIPs films were formed on the surface of Fe3O4@SiO2 by the copolymerization of
      vinyl end groups with functional monomer, methacrylic acid, cross-linking agent,
      ethylene glycol dimethacrylate, the initiator azo-bis-isobutyronitrile and
      template molecule, sulfamethazine. The morphology, magnetic, adsorption and
      recognition properties of Fe3O4@MIPs NPs were characterized using transmission
      electron microscope (TEM), scanning electron microscope (SEM), Fourier transform
      infrared (FT-IR) spectrometer, vibrating sample magnetometer (VSM) and re-binding
      experiments. The results showed that the binding sites of Fe3O4@MIPs were good
      accessibility, fast adsorption rate and the maximum adsorption capacity of
      Fe3O4@MIPs to SMZ was 344.8 MUg g-1. The selectivity of the obtained Fe3O4@MIPs
      NPs were elucidated by the different rebinding capability of SMZ and structural
      related sulfonamides in the mixed solution. The results indicated that the
      Fe3O4@MIPs had high imprinting factor 9.5 and significant selectivity. A method
      was developed for enrichment and determination of SMZ in the poultry feed samples
      with recoveries of duck and chicken feed ranging from 63.3 to 76.5% and 68.7 to
      74.7%, respectively and the relative standard deviations (RSD) (<6.7%).

PMID- 22663978
TI  - Gas chromatography using resistive heating technology.
AB  - Air bath ovens are standard in conventional gas chromatography (GC) instruments
      because of their simplicity and reliability for column temperature control.
      However, their low heating rates, high power consumption and bulky size are in
      conflict with the increasing demands for fast separation and portable
      instrumentation. The deficiencies of air bath ovens can be eliminated using
      resistive heating technology, as the column is conductively heated by compact
      resistive heaters with low thermal mass. Resistive heating methods were employed
      in the early years of GC history, and they are emerging again as instrumentation
      is becoming more compact and sophisticated. Numerous designs have been tested and
      some have been successfully commercialized. Development of portable GC systems,
      including lab-on-a-chip devices, greatly benefits from the use of small, low
      power resistive heating hardware. High speed GC separations using conventional
      instruments also can be best achieved with resistive heating modules. Despite
      some of its own inherent disadvantages, including efficiency loss, complex
      manufacturing and inconvenient column maintenance, resistive heating is expected
      to rapidly become a mature technology and even replace oven heating in the not-to
      distant future.

PMID- 22663977
TI  - Identification of O-methyl-(-)-epicatechin-O-sulphate metabolites by mass
      spectrometry after O-methylation with trimethylsilyldiazomethane.
AB  - (-)-Epicatechin, an abundant dietary polyphenol found mainly in cocoa and tea, is
      known to extensively undergo metabolism after ingestion giving rise to a complex
      series of conjugated metabolites including numerous isomers. In the present
      study, the combination of fractionation, chemical derivatization and various mass
      spectrometric approaches is described to determine the exact position of sulphate
      group in methylated epicatechin metabolites. Four O-methyl-(-)-epicatechin-O
      sulphate metabolites isolated from human urine samples were derivatized under
      mild condition using trimethylsilyldiazomethane (TMSD) in the presence of
      methanol. The resulting methylated reaction products were then analyzed by high
      resolution and multistage mass spectrometry for the subsequent identification of
      the sulphate positional isomers. Results show that O-methylation affects the
      charge delocalization in negatively charged ions and hereby the fragmentation
      pattern of the sulphate isomers allowing the identification of diagnostic ions.
      In addition, this study demonstrates that methoxy derivatives of polyphenol
      metabolites can be prepared using TMSD. Subsequently, the localization of the
      sulphate group in the polyphenol metabolites can be achieved by analyzing the
      methoxy derivatives by multistage mass spectrometry. Using an enzymatic reaction
      for identification of the O-methyl position, and a chemical O-methylation with
      TMSD follow by high resolution and multistage tandem MS for the identification of
      the sulphate group position, we were able to identify the previously unknown O
      methyl-(-)-epicatechin-O-sulphate. Accordingly, we identified 3'-O-methyl-(-)
      epicatechin-5-O-sulphate and 3'-O-methyl-(-)-epicatechin-7-O-sulphate as the main
      O-methyl-(-)-epicatechin-sulfates(-)-epicatechin metabolites in humans.

PMID- 22663979
TI  - The genome of wine yeast Dekkera bruxellensis provides a tool to explore its food
      related properties.
AB  - The yeast Dekkera/Brettanomyces bruxellensis can cause enormous economic losses
      in wine industry due to production of phenolic off-flavor compounds. D.
      bruxellensis is a distant relative of baker's yeast Saccharomyces cerevisiae.
      Nevertheless, these two yeasts are often found in the same habitats and share
      several food-related traits, such as production of high ethanol levels and
      ability to grow without oxygen. In some food products, like lambic beer, D.
      bruxellensis can importantly contribute to flavor development. We determined the
      13.4 Mb genome sequence of the D. bruxellensis strain Y879 (CBS2499) and deduced
      the genetic background of several "food-relevant" properties and evolutionary
      history of this yeast. Surprisingly, we find that this yeast is phylogenetically
      distant to other food-related yeasts and most related to Pichia (Komagataella)
      pastoris, which is an aerobic poor ethanol producer. We further show that the D.
      bruxellensis genome does not contain an excess of lineage specific duplicated
      genes nor a horizontally transferred URA1 gene, two crucial events that promoted
      the evolution of the food relevant traits in the S. cerevisiae lineage. However,
      D. bruxellensis has several independently duplicated ADH and ADH-like genes,
      which are likely responsible for metabolism of alcohols, including ethanol, and
      also a range of aromatic compounds.

PMID- 22663980
TI  - Microbiology of raw milk in New Zealand.
AB  - The results of this study demonstrate the occurrence of the non-spore-forming
      pathogens, Staphylococcus aureus, Escherichia coli (total count and O157:H7),
      Listeria, Campylobacter and Salmonella, in New Zealand's raw milk supply. Samples
      of raw milk were collected monthly within five major dairying regions over one
      year. Each month, samples from five randomly selected farm vats in each region
      were collected for analysis (297 samples in total). Methods based on plate count
      techniques were used to enumerate S. aureus and E. coli. Enrichment methods in
      combination with a modified most probable number detection method were used to
      monitor samples for the presence of E. coli O157:H7, Listeria, Campylobacter and
      Salmonella. Salmonella was not detected in this study, and Campylobacter was
      isolated once (0.34%). E. coli was present at <100 cfu/ml in 99% of samples and
      exceeded 10(3)cfu/ml in 0.7% of samples. E. coli O157:H7 was not detected whereas
      non-pathogenic E. coli O157 strains (i.e. lacking genes for stx1, stx2, eae and
      Hly A) were detected in 1% of samples. S. aureus was not detected (<1 cfu/ml) in
      21% of samples; levels were >1 but <100 cfu/ml in 60% of samples and on one
      occasion (0.34%) S. aureus exceeded 10(4)cfu/ml. L. monocytogenes was isolated
      from 0.68% of samples and L. innocua was present in 4% of samples. The results
      demonstrate that raw milk sampled from farm vats in New Zealand, as in other
      countries, inevitably contains recognised pathogens and, hence, control by
      pasteurisation or an equivalent treatment of raw milk remains paramount. Even so,
      the prevalence of most of these pathogens was lower than those reported in many
      of the studies performed in other countries.

PMID- 22663981
TI  - Water activity in dry foods containing live probiotic bacteria should be
      carefully considered: a case study with Lactobacillus rhamnosus GG in flaxseed.
AB  - This study evaluated the effect of water activity on the long-term storage
      stability of the probiotic Lactobacillus rhamnosus GG (LGG) in a dry food matrix.
      Viability of LGG was further studied in a crushed flaxseed matrix - a new
      possible product matrix to deliver probiotics - as well as in reference matrices
      as maltodextrin. Three different water activities (a(w)=0.11, 0.22 and 0.43) were
      used, and preparations were stored at room temperature for up to 14months. The
      viability of LGG was less dependent on the matrix used, but strongly dependent on
      the water activity. Viability in flaxseed was lost rapidly with a(w) 0.43: with
      a(w) 0.22 the reduction was 2.4 log(10) units and with a(w) 0.11 the reduction of
      viability was only 0.29 log(10) units during the entire storage time. Taken
      together, regulating water activity to a low value may offer possibilities for
      extending the shelf life of dry probiotic products.

PMID- 22663982
TI  - Categories of donation after cardiocirculatory death.
AB  - The interest in donation after cardiocirculatory death (DCD) was renewed in the
      early 1990s, as a means to partially overcome the shortage of donations after
      brain death. In some European countries and in the United States, DCD has become
      an increasingly frequent procedure over the last decade. To improve the results
      of DCD transplantation, it is important to compare practices, experiences, and
      results of various teams involved in this field. It is therefore crucial to
      accurately define the different types of DCD. However, in the literature, various
      DCD terminologies and classifications have been used, rendering it difficult to
      compare reported experiences. The authors have presented herein an overview of
      the various DCD descriptions in the literature, and have proposed an adapted DCD
      classification to better define the DCD processes, seeking to provide a better
      tool to compare the results of published reports and to improve current
      practices. This modified classification may be modified in the future according
      to ongoing experiences in this field.

PMID- 22663983
TI  - Knowledge, attitudes and commitment toward organ donation among nursing students
      in Hong Kong.
AB  - BACKGROUND: Organ donation is the major component for transplant programs;
      however, the rate of organ donation is relatively low in Asia. Therefore,
      understanding the attitude and knowledge of individuals that affect their
      willingness to commit as an organ donor is crucial to develop effective
      educational programs that raise public awareness and commitment toward organ
      donation. The current study aims to identify the knowledge level, attitude, and
      commitment toward organ donation among nursing students in a local university.
      METHODS: A questionnaire was developed and distributed to all full-time nursing
      students of undergraduate and master programs in a university at Hong Kong.
      RESULTS: A total of 362 students completed the questionnaire, including 87 males
      and 257 females. The mean age of the students was 22.6 years. A total of 147
      students (40.6%) had registered for organ donation. Students on average could
      correctly answer 23.7 out of 33 questions (71.8%) regarding their knowledge on
      organ donation and transplantation. With regard to attitude toward organ
      donation, students obtained a mean score of 70.2. Univariate analysis revealed
      that year of study, religion, and attitude were significantly associated with
      commitment toward organ donation. In logistic regression analysis, year of study
      (odds ratio [OR] for year 2, 1.961, 95% confidence interval [CI], 1.006-3.824; OR
      for year 3, 6.915, 95% CI, 2.835-16.868; and OR for year 4, 4.845, 95% CI, 2.071
      11.334) and attitude (OR, 1.087, 95% CI, 1.049-1.126) were significantly
      associated with commitment toward donation after adjusting the age, gender, and
      study program. CONCLUSION: Attitude and year of study were strongly correlated
      with commitment toward organ donation; therefore, educational or promotional
      materials should be provided to improve the attitude of students toward organ
      donation.

PMID- 22663984
TI  - Oxygen inhalation improves survival time of mice with acute intra-abdominal
      hypertension and protects liver cells.
AB  - OBJECTIVE: The objectives of this study were to establish a mouse model of
      sustainable, stable acute intra-abdominal hypertension (IAH), seeking to observe
      the survival time and liver functions at different intra-abdominal pressures
      (IAP), and to investigate changes after oxygen therapy. METHODS: Sixty Kunming
      mice were assigned to 4 groups with an average of 15, 20, 30, or 40 cmH(2)O IAP.
      The 40 cmH(2)O group seemed to be appropriate for follow-up experiments. The 45
      mice added to the cohort were assigned into 3 groups administered an average of
      50%, 80%, and 100% O(2), respectively. Liver and blood samples were used to
      compare the rates of apoptosis using the TUNEL assay as well as alanine
      aminotransferase (ALT), aspartate aminotransferase (AST); Caspase-3, 9, MDA, and
      SOD concentrations. RESULTS: Most animals in the 15 and 20 cmH(2)O groups
      survived 8 hours. The average survival for the 30 and 40 cmH(2)O groups were 4.54
      +/- 0.54 hours and 2.04 +/- 0.44 hours, respectively (P < .01). As the oxygen
      concentration increased, the survival time was prolonged among the 40 cmH(2)O IAP
      group (P < .01), and the member of apoptotic hepatic cells decreased (P < .01),
      with a concomittent decrease in caspase 3 and 9 as well as malondialdehyde,
      although superoxide dismutase showed the opposite results. CONCLUSION: The
      present work using a mouse model for acute IAH showed oxygen inhalation to
      improve host survival and protect liver cells.

PMID- 22663985
TI  - Expression of transient receptor potential melastatin 7 up-regulated in the early
      stage of renal ischemia-reperfusion.
AB  - BACKGROUND: Transient receptor potential melastatin 7 (TRPM7), a bifunctional
      protein with kinase and ion channel activities, was first reported in 2001. Later
      studies suggested that the functions of TRPM7 related to cancer, ischemic injury,
      and hypertension. METHODS: We examined whether TRPM7 expression changed in renal
      ischemia-reperfusion injury (RIRI). Seventy male Sprague-Dawley rats weighing 220
      250 g were randomly divided into 7 groups of 7 rats each; every group had a sham
      operated cohort of 3 rats. After the right kidney was removed, the rats underwent
      45 minutes of left renal artery occlusion followed by reperfusion for 1, 12, 24,
      48, 72, or 96 hours. There after the expression of TRPM7 messenger RNA (mRNA) was
      measured using real-time polymerase chain reaction (RT-PCR) and the protein using
      Western blot. RESULTS: Compared with the control group, the expression of TRPM7
      mRNA was significantly up-regulated at 24 hours after ischemia-reperfusion. We
      set the expression of TRPM7 mRNA of the control group as the baseline (1.0), with
      the 1-hour, 12-hour, 24-hour, 48-hour, 72-hour and 96-hours showing 2.83, 3.16,
      3.95, 0.31, 0.82, and 1.13, respectively (n = 7; P < .05). TRPM7 protein
      expression showed the same trends as the mRNA. The main change in TRPM7 protein
      was located in tubular cells. CONCLUSIONS: The expressions of TRPM7 mRNA and
      protein levels was up-regulated at 24 hours after renal ischemia.

PMID- 22663986
TI  - Caffeic acid phenethyl ester effects in the kidney during ischemia and
      reperfusion in rats anesthetized with isoflurane.
AB  - BACKGROUND: The purpose of this investigation was to examine the effect of
      caffeic acid phenethyl ester (CAPE) in renal ischemia/reperfusion injury in rats
      anesthetized with isoflurane (iso). METHODS: We randomly assigned 26 male Wistar
      rats anesthetized with isoflurane, intubated and mechanically ventilated to 3
      groups: G1 (controls; n = 8), G2 (CAPE; n = 10), and G3 (ethanol; n = 8). Mean
      arterial pressure was monitored for anesthetic control. Intraperitoneal CAPE (G2)
      or ethanol (G3) injections were administered 40 minutes before left renal
      ischemia. All animals underwent right nephrectomy and the left kidney was
      submitted to ischemia for 25 minutes. Serum creatinine (cr) values were
      determined at the beginning (M1), end (M2), and 24 hours after the experiment
      (M3) upon intracardiac blood samples. The left kidney was removed for histologic
      analysis, using a scale for tubular necrosis (0-5, injury maximum). Statistical
      analysis was applied to serum creatinine and histological score injury
      considering statistical differences to be significant when P < .05. RESULTS: The
      cr values in the CAPE were significantly higher at M2 (0.8 mg/mL; P = .0012) and
      M3 (3.7 mg/mL; P = .0014) than the control (0.5 and 0.9 mg/mL) or G3 (0.6 and 1.0
      mg/mL), respectively. Histologic examination showed the CAPE group to display
      more pericapsular tubular necrosis (3.0 [2.0; 3.0]) than the G1 group (2.0 [1.0;
      2.0]) or G3 group (1.5 [1.0; 2.0]; P < .001). The CAPE group displayed more
      medullary tubular necrosis (2.0 [2.0; 3.0] than G1 (2.0 [1.0; 2.0] or G3 (1.0
      [0.0; 2.0]; P < .001). CONCLUSION: CAPE promoted greater functional and anatomic
      renal injury when rats were anesthetized with iso than control or ethanol groups,
      as demonstrated by histologic analysis and serum values.

PMID- 22663987
TI  - Defining the nonreturn time for intestinal ischemia reperfusion injury in mice.
AB  - Among the abdominal organs, the intestine is probably the most sensitive to
      ischemia reperfusion injury (IRI), a phenomenon that occurs in many intestinal
      disorders. Few studies have reported in detail the impact of intestinal ischemia
      time in mice. We evaluated the effect of various warm intestinal ischemia times
      in an intestinal IRI model in mice. Adult male Balb/c mice were divided into 4
      groups that differed in intestinal ischemia time: G1, 30; minutes; G2, 35
      minutes; G3, 40 minutes; and G4, 45 minutes. Histological evaluation showed
      average Park scores as follows: G1 0.6 +/- 0.55; G2 1.8 +/- 0.45; G3 4.8 +/-
      2.25; and G4 5 +/- 1.79. All animals from G1 survived 30 hours. G2 animals showed
      intermediate behavior with all succumbing between 18 and 30 hours postprocedure.
      G3 and G4 displayed similar survival results with animals succumbing before 6
      hours after intestinal reperfusion. These data showed that Park index scores of 3
      or higher were related to early death. We concluded that the 5 minutes between 35
      and 40 minutes is the critical limit, after which all mice die after reperfusion.
      This result may represent a valuable tool for future research in mice.

PMID- 22663988
TI  - Technical modifications of hand-assisted retroperitoneoscopic living donor
      nephrectomy: a single-center experience.
AB  - OBJECTIVES: To report a single-center experience and technical modifications of
      hand-assisted retroperitoneoscopic living donor nephrectomy (HARLDN). METHODS: A
      total of 78 living donors underwent HARLDN from June 2004 to November 2009. We
      used a three-port, finger-dissecting, routine retroperitoneal approach. After
      almost complete mobilization of the kidney, the renal pedicle was dissected to
      expose the renal vessels. The ureter was dissected and divided at the level of
      the iliac vessels. An approximately 7-cm Gibson incision was made as the hand
      assisted port. The surgeon's hand was introduced through this incision directly.
      With hand assistance, the renal artery was clipped using two Hem-o-lok clips at
      the proximal end, and then sheared by scissors without any clips on the kidney
      side. The renal vein was controlled similarly. Then the kidney was rapidly
      removed through the incision by hand. RESULTS: HARLDN was effectively and safely
      completed in 78 (100%) donors. No conversion to an open operation was necessary.
      The mean operative time and mean warm ischemic time were 121 minutes (range, 90
      134) and 146 seconds (range, 112-247) respectively. The mean blood loss was 61 mL
      (range, 32-85). Clavien 1 complications including subcutaneous emphysema in 5.1%
      (4/78). The mean visual analog scales on postoperative days 1 to 5 were: 2.5,
      1.2, 0.8, 0.5, and 0.1, respectively. The mean time to resume oral diet was 1.5
      days. The mean hospital stay was 4.5 days (range, 4-5). The mean level of
      postoperative serum creatinines of the donors at 7 days and 1 month thereafter
      were 1.06 mg/dL (range, 0.74-1.43) and 1.15 mg/dL (range, 0.79-1.61) mg/dL,
      respectively. The mean level of postoperative serum creatinines of the recipients
      at 7 days and 1 month were 1.40 mg/dL (range 0.81-1.67) and 1.52 mg/dL (range,
      0.76-1.83), respectively. The mean incision length was 6.5 cm (range, 6.0-7.2).
      CONCLUSIONS: The modified HARLDN combines the purely laparoscopic technique with
      quicker, safer organ retrieval by the open access.

PMID- 22663989
TI  - Deleterious influence of prolonged warm ischemia in living donor kidney
      transplantation.
AB  - BACKGROUND: Recent studies investigating early graft function (EGF) after living
      donor kidney transplantation (LDKT) identified prolonged warm ischemia time (WIT)
      as a risk factor for the occurrence of poor EGF. The latter is associated with
      long-term graft loss; therefore the question arises whether prolonged WIT affects
      long-term outcomes in LDKT. METHODS: Data were collected on 472 consecutive adult
      LDKTs. Patients were divided according to the total WIT into 3 groups with short
      (<30 minutes), intermediate (30-45 minutes), or prolonged (>45 minutes) WIT.
      RESULTS: Of all patients, 193 (40.9%) experienced short, 249 (52.8%)
      intermediate, and 30 (6.4%) prolonged WIT. Prolonged WIT was a significant risk
      factor for the occurrence of poor EGF with an adjusted odds ratio of 4.252 (95%
      confidence interval [CI), 1.914 -9.447). Long-term graft survival was impaired in
      patients with prolonged WIT, with an adjusted hazard ratio of 3.163 (95% CI,
      1.202-8.321). Multivariate analysis revealed determinants of prolonged WIT,
      including laparoscopic procurement, recipient overweight, right donor kidney, and
      multiple renal arteries. CONCLUSION: Prolonged WIT impairs long-term graft
      survival in LDKT. This finding underlines the need to develop strategies to avoid
      the occurrence of prolonged WIT in LDKT.

PMID- 22663990
TI  - Early renal transplantation after donor renal angiography affects initial graft
      function.
AB  - BACKGROUND: Renal angiography of a living donor is a common radiologic
      examination before transplantation. However, the contrast agent used during this
      procedure can cause contrast nephropathy. There are insufficient data regarding
      whether this radiocontrast exposure detoriates renal function and survival after
      transplantation. In this study, we analyzed the effects of radiocontrast exposure
      to donors before transplant surgery on the incidence of delayed graft function
      (DGF) and on the outcomes of recipients at 1 year posttransplantation. METHODS:
      We divided 80 living donor transplantations according to the duration between the
      renal angiography and the transplantation procedure: Group 1 as early
      transplantation at <= 20 days (n = 42) versus group 2 of late transplantation at
      >= 20 days (n = 38). We retrospectively collected acute rejection episodes and
      graft survival at 1 year, monthly serum creatinine values of, DGF, proteinuria at
      1 month, GFR at posttransplant day 3 month 1, and 1 year. RESULTS: There were 10
      group 1 recipients (23.8%) and 2 group 2 (5.3%) subjects who experienced >= 1
      acute rejection episode in the 1st posttransplant year (P = .02); 1 patient in
      each group experienced graft loss at 1 year (P = .941). DGF was observed in 9
      (22%) versus 1 patient (2.6%) in group 2 (P = .009). Posttransplant day 3
      creatinine values were significantly higher (P = .005) with significantly lower
      GFR values (P = .043) in group 1. However, creatinine and GFR levels were similar
      at 1 month and 1 year. Month 1 proteinuria levels were significantly higher in
      group 1 (P = .014). There was a significant negative correlation between renal
      angiography time and month 1 proteinuria (P = .014). CONCLUSIONS: Early renal
      transplantation (within 2 weeks after renal angiography) in living kidney donors
      can detoriate initial graft function and cause DGF.

PMID- 22663991
TI  - Role of human leukocyte antigen, donor-specific antibodies, and their impact in
      renal transplantation.
AB  - INTRODUCTION: The clinical significance of the presence of antibody against human
      leukocyte antigen (HLAb) and donor-specific antibodies (DSAb) prior to renal
      transplantation remains unclear. This study was done to assess the impact of HLAb
      and DSAb on graft function, rejection episodes, and graft survival in renal
      transplantation. METHODS: The Luminex (Luminex, Austin, Texas, United States) is
      a solid-phase assay using micro-spheres and it is more sensitive at detecting
      human leukocyte antigen (HLA) antibodies than conventional tests. This
      retrospective analysis involved 141 consecutive renal transplant recipients
      between May 2007 and 2009 and with a minimum of 2 years of follow-up. RESULTS:
      Luminex was positive for HLA class I in 35 and negative in 106; similarly class
      II positivity was noted in 23 and negative in 118. The DSAb were positive in 33
      and negative in 108 recipients. The HLA class I, class II, and DSA-positive
      groups showed no difference in renal function assessed by estimated glomerular
      filtration rate (eGFR) at 2 years (52 +/- 29 vs 52 +/- 22; 56 +/- 29 vs 51 +/-
      29; 48 +/- 18 vs 53 +/- 19; P = not significant [NS]). But rejection episodes at
      1 year were significantly high in HLA class I and DSAb-positive group (17/35 vs
      27/106; P = .019 and 16/33 vs 29/108; P = .035). The rejection episodes in the
      HLA class II-positive group did not show any difference when compared with the
      negative group (9/23 vs 40/118; P = .63). Graft survival was not affected by
      positivity to any of these antibodies at 2 years. CONCLUSION: Having HLA class I,
      class II, and DSAb does not have any influence on early and intermediate graft
      function. The HLA class I and DSAb positivity increases rejection episodes within
      1 year in renal transplantation. Graft survival was not affected by class I,
      class II, and DSAb at 2 years.

PMID- 22663992
TI  - Temporary inactive status on renal transplant waiting list: causes, risk factors,
      and outcomes.
AB  - Approximately 30% of all patients listed for a kidney transplant in the United
      States are on inactive status. The consequences of temporary inactivation and
      rates of transplantation in this group of patients have not been reported. We
      undertook a retrospective cohort study at our transplant center examining all
      patients listed between 2001 and 2007. We examined the rate of inactivation, risk
      factors, duration, and outcomes including transplantation rates and patient
      survival while on the waiting list and after transplantation. There were 436
      patients included in the analysis; 322 (73.9%) were never inactivated and 114
      patients (26.1%) were temporarily inactive. The most common causes for
      inactivation were cardiovascular and suspected malignancy. Time to reactivation
      was similar among different causes. Waiting times for transplantation (excluding
      time of inactivation) was 18.7 +/- 0.9 versus 39.9 +/- 2.3 months for active
      compared with temporarily inactive patients (log-rank P < .0001). Sixty-five
      percent of patients were reactivated within 24 months. Approximately one-third of
      patients were never reactivated. Patient survival was similar among both groups.
      Temporary inactivation is an independent risk factor for a prolonged waiting time
      even if time of inactivation is not accounted for. Effective strategies for
      monitoring patients temporarily inactive on the waiting list should be developed.

PMID- 22663993
TI  - Influence of cytokine gene polymorphisms on graft rejection in Turkish patients
      with renal transplants from living related donors.
AB  - INTRODUCTION: Certain cytokine gene polymorphisms (CGPs) have been shown to be
      associated with renal transplant rejection or graft outcomes. We sought to
      evaluate the relationship between gene polymorphisms in patients with acute
      rejection episodes (rejection group, RG, n = 19) versus those with stable graft
      function (nonrejection group, NRG, n = 71) in comparison with healthy control
      subjects (HCG, n = 150). The follow-up time period was 18 months. In the present
      study, 22 single nucleotide polymorphisms distributed across 13 cytokine and
      cytokine receptor genes were genotyped by polymerase chain reaction sequence
      specific primers (PCR-SSP) using the Heidelberg kit. RESULTS: The interleukin-2
      (IL-2) TT/GT haplotype was observed among 36.8% of patients in the RG and 6.7% of
      those in the HCG but not in any NRG patient (P < .0001; .0007). The IL-2 GG/TT
      haplotype was observed among 13 NRG and 9 HCG patients (P = .007). The IL-2 GG/GG
      haplotype was noted in 18.7% of HCG and 4.2% of NRG patients (P = .0033) and the
      IL-2 TT/TT haplotype in 5 and 8 patients of NRG and HCG, respectively, but not in
      any RG patient (P > .05). The transforming growth factor beta1 CG/CC haplotype
      was noted in 15 NRG (21.1%) and 4 HCG patients but not any RG (P < .0001). The IL
      2 + 166 GT genotype was detected in 36.8% of RG, 8.5% of NRG, and 14.7% of HCG
      patients (P = .005, .0244). The IL-2 -330 GG genotype was demonstrated in 32
      healthy controls and 3 nonrejection transplant patients (P = .0007). Significant
      differences were found between NRG and HCG for IL-6 565 AG, IL-1 beta -511 TT and
      +3962 CC/CT/TT genotypes. DISCUSSION: We observed significant differences among
      the frequencies of IL-2 gene polymorphisms between the RG and the NRG, which were
      consistent with previous clinical but not in vitro studies.

PMID- 22663994
TI  - Evaluation of serum cystatin C for diagnosis of acute rejection after renal
      transplantation.
AB  - OBJECTIVE: To evaluate the clinical value of serum cystatin C (ScysC) for the
      diagnosis of an acute rejection episode after renal transplantation. METHODS: The
      76 recruited renal transplant patients included 43 without and 33 with an acute
      rejection episode. We determined the values of serum creatinine (Scr), blood urea
      nitrogen (BUN), beta(2) microglobulin (beta(2)-MG), uric acid (UA), and ScysC
      before surgery and at 1, 3, 5, 7, 14, 30, and 90 days thereafter. The glomerular
      filteration rate (GFR) was measured by (99m)Tc-DTPA to evaluate correlations.
      RESULTS: No significant difference was observed between the groups before surgery
      (P > .05). In the rejection-free group ScysC was decreased by 48.1% at 1/day
      after surgery which was greater than the other cohorts. In the rejection group at
      day 3 the ScysC increased which was earlier than others. The highest coefficient
      correlation was observed between ScysC and GFR. The AUC(ROC) of ScysC was greater
      than all of the others. CONCLUSION: ScysC was a more sensitive marker to detect
      changes in renal function than Scr, BUN, beta(2)-MG or UA; therefore it can be
      used to predict an acute rejection episode after transplantation.

PMID- 22663995
TI  - The role of splenectomy in the setting of refractory humoral rejection after
      kidney transplantation.
AB  - Living donor kidney transplantation remains the best option for presensitized
      recipients to avoid excessive time on the waiting list. However, the possibility
      for a positive crossmatch with a potential living donor is high. A
      desensitization protocol may be required to avoid antibody-mediated rejection
      (AMR). Current protocols are not always effective to prevent AMR and in some
      cases fail to convert subjects to a negative crossmatch before transplantation.
      From March 2006 to January 2011, the 11 presensitized patients who displayed AMR
      after living donor kidney transplantation underwent splenectomy as a rescue
      procedure due to failure of standard rejection treatments. Splenectomy was
      considered to be effective in six recipients who normalized their renal function
      without the need for other immunomodulating therapy. Our analysis suggested that
      splenectomy can be successfully performed alone or in association with other
      treatments like bortezomib or rituximab to overcome severe AMR.

PMID- 22663996
TI  - Clinical relevance of sHLA-G-mediated with better graft acceptance in early
      posttransplantation.
AB  - The aim of this study was to measure the level of soluble human leukocyte antigen
      (sHLA-G) in renal transplant patients, to determine the relationship between
      these levels and the occurrence of acute rejection episodes, and to identify
      their influence on graft acceptance early posttransplantation. sHLA-G, as
      measured by an enzyme-linked immunosorbent assay, was significantly increased (P
      < .01) early posttransplantation (3 months); the other group maintained low
      levels throughout the study. The latter group displayed a high incidence of acute
      rejection episodes and a lower clearance of serum creatinine with a longer period
      for hemoglobin to recover to normal (P < .01). These results suggested that HLA-G
      participates in the induction of immunologic tolerance in these recipients.

PMID- 22663997
TI  - Kidney transplantation in hepatitis C-positive recipients: does type of induction
      influence outcomes?
AB  - BACKGROUND: Kidney transplantation in hepatitis C virus-seropositive (HCV+)
      recipients improves survival compared to staying on the waiting list. A concern
      for using depleting (versus nondepleting) induction agent during kidney
      transplantation in HCV+ recipients is the possibility that the associated
      enhanced immunosuppression might favor the progression of hepatitis C infection,
      leading to adverse outcomes. METHODS: Utilizing data from the Organ Procurement
      and Transplant Network, we identified HCV+ patients >= 18 years of age who
      underwent deceased donor kidney (DDK) transplants from either HCV+ or HCV- donors
      between 1998 and 2008. Patients were divided into two groups based on the
      induction type they received during the transplant: depleting agent (rabbit
      antithymocyte globulin or alemtuzumab) or nondepleting agent (basiliximab or
      daclizumab) groups. Unadjusted and adjusted graft and patient survivals (Cox
      regression) between the groups were compared. RESULTS: A total of 3490 HCV+ DDK
      recipients were identified (1859 in the depleting and 1631 in the nondepleting
      groups). When compared to nondepleting agent, adjusted graft (hazard ratio [HR]
      1.11, 95% confidence interval [CI] 0.96-1.28, P = .16) and patient (HR 1.15, 95%
      CI 0.93-1.42, P = .2) survivals were similar with depleting agent induction. HCV
      donor seropositivity did not adversely impact either graft (HR 1.11, 95% CI 0.96
      1.29, P = .17) or patient (HR 1.15, 95% CI 0.93-1.42, P = .2) outcomes.
      CONCLUSIONS: Our analysis supports the practice of transplanting HCV+ donor
      kidneys into HCV+ recipients to alleviate waiting list burden. Recipient HCV
      positivity should not influence selection of induction agent.

PMID- 22663998
TI  - Biomarkers for monitoring therapeutic side effects or various supratherapeutic
      confounders after kidney transplantation.
AB  - Although the development of novel immunosuppressants dramatically decreased the
      incidence of acute allograft rejection episodes, long-term allograft survival has
      not improved due to various postoperative confounders. These confounders include
      heterologous immunity by cytomegalovirus (CMV) infection, nephrotoxicity of
      immunosuppressants, ureteral complications, and onset of the original renal
      disease in the graft, which can mislead physicians from the actual diagnosis.
      Early and precise discrimination of these complications by using noninvasive
      biomarkers will benefit the patients at high-risk and be instructive in directing
      effective and timely therapies whenever necessary.

PMID- 22663999
TI  - Assessment of cardiovascular risk factors after renal transplantation: a step
      towards reducing graft failure.
AB  - BACKGROUND: Prolongation of renal allograft survival a considerable challenge.
      The primary cause of renal graft failure is recipient death and cardiovascular
      disease is the leading cause of mortality. We assessed the management of
      hypertension, dyslipidemia and diabetes mellitus (DM) in a protocol-driven renal
      transplant clinic. METHODS: We reviewed 128 patients who received a renal
      allograft between 2004 and 2008 at our institution. Blood pressure (BP), low
      density lipoprotein (LDL) and hemoglobin AlC (HbAlC) were assessed annually for
      up to 5 years. Results were compared with the Kidney Disease: Improving Global
      Outcomes guidelines which target BP at <= 130/80 mmHg, LDL <= 100 mg/dL, and
      HbAlC <= 7.5%. Use of statins and antihypertensive medications was reviewed. Chi
      square and t tests were used for analysis. RESULTS: A history of hypertension,
      dyslipidemia, and DM were present in 96.1%, 60.9%, and 43.8%, respectively. The
      percentage of patients on >= 3 antihypertensive medications, statins, and other
      lipid-lowering medications were 38.01%, 44.5%, and 17.2%, respectively. One-year
      posttransplant targets for BP, LDL, and HbAlC were achieved in 41.4%, 71.7%, and
      70.5% of patients, respectively. Five-year posttransplant target BP, LDL, and
      HbAlC were achieved in 55%, 91.7%, and 88.9% of patients, respectively.
      CONCLUSIONS: Even in a university-based clinic with protocols designed to improve
      compliance, treatment goals for BP, LDL, and HbAlC were not achieved in a
      substantial number of patients, especially in the first year posttransplantation.
      Better strategies are needed to meet treatment objectives and prevent untoward
      outcomes.

PMID- 22664000
TI  - New immunosuppressive therapies and surgical complications after renal
      transplantation.
AB  - BACKGROUND: To analyze the association between the principal immunosuppressive
      drugs (mycophenolate mofetil, calcineurin inhibitors and mammalian target of
      rapamycin [mTOR] inhibitors) used in the routine management of kidney transplant
      patients and the development of postoperative surgical complications. MATERIALS
      AND METHODS: We analyzed 415 kidney transplants, studying the influence of
      various immunosuppressive regimens on the main postoperative surgical
      complications. RESULTS: The mean follow-up for the entire group was 72.8 months
      (+/- 54.2 SD). Patients treated with myeophonolate mofetil (MMF) and cyclosporine
      (n = 121) experienced a higher frequency of wound eventration odds ratio [OR],
      5.2; 95% confidence interval [CI], 1.2-23.5; P = .03) compared with azathioprine
      and cyclosporine (n = 71). Compared with transplant recipients treated with
      tacrolimus and MMF (n = 181), transplant recipients treated with cyclosporine and
      MMF (n = 121) had a significantly greater frequency of wound eventration (OR,
      3.7; 95% CI, 1.5-9.5; P = .005), urologic (OR, 2; 95% CI; 1.02-3.9; P = .04),
      wound (OR; 2.2; 95% CI; 1.07-4.6; P = .03), late (OR, 1.7; 95% CI; 1.01-3.03; P =
      .04), and Clavien grade 3 surgical complications (OR; 1.9; 95% CI, 1.1-3.37; P =
      .01). Patients treated with mTOR inhibitors (n = 26) had higher rates of
      lymphocele (OR, 3.6; 95% CI, (1.1-11.4; P = .002) compared with those who
      received tacrolimus (n = 197). CONCLUSIONS: New immunosuppressive drugs have
      improved short-term functional results; however, in some cases they seem to
      increase surgical complications rates.

PMID- 22664001
TI  - Development and validation of a specific questionnaire for evaluating the impact
      of gastrointestinal symptoms on the health-related quality of life of transplant
      patients.
AB  - BACKGROUND: Transplant patients receiving immunosuppressant treatment suffer
      gastrointestinal symptoms (GIS) limiting their health-related quality of life
      (HRQOL) and causing dose rediuctions and discontinuations. METHODS: This
      observational, multicenter, cross-sectional study aims to develop and validate a
      questionnaire for detecting and quantifying the impact of GIS on the HRQOL of
      patients with functioning organ transplants. We developed a pilot version of the
      questionnaire SIGIT-QOL (Impact of Gastrointestinal Symptoms on Quality Of Life)
      and then evaluated the feasibility, validity, and reliability. We consecutively
      recruited 274 solid organ transplant patients from 20 hospitals. Sociodemographic
      and clinical data were collected. Patients completed the SIGIT-QOL and
      Gastrointestinal Quality of Life Index-GIQLI- questionnaires. RESULTS: Mean age
      was 52.7 (SD, 7.59) and 181 were male; 43.4% showed an episode of GIS since
      transplantation (3-12 months before). Of all patients, 95.3% completed the SIGIT
      QOL. Mean time of completion was 6.49 minutes. Exploratory factorial analysis
      identified a 1-dimensional structure (42% of total variance). Internal
      consistency was high (Cronbach's alpha, 0.889). A significant association was
      found between the SGITI-QOL and the presence of GIS (P < .01). Finally,
      correlation coefficients between SIGIT-QOL and GIQLI were moderate-high except
      for Social Function. CONCLUSION: The brief SIGIT-QOL questionnaire can detect and
      quantify the GIS and their impact on the HRQOL of solid organ transplant
      patients.

PMID- 22664003
TI  - Urologic de novo malignancies after kidney transplantation: a single center
      experience.
AB  - INTRODUCTION: Urologic cancers are the second or third most common malignancies
      in renal transplant (RT) recipients. This study sought to determine the incidence
      of and identify possible risk factors for urologic malignancies among patients
      who underwent transplantation at our center. METHODS: This retrospective, single
      center cohort included 836 patients who underwent transplantation from 1994 to
      2011 who remained under our care. A review of their medical records revealed 63
      subjects with de novo cancer, including 21 with urologic malignancies (2.5%). We
      analyzed demographic and clinical data of cancer versus noncancer patients with
      differences considered to be significant at P < .05. RESULTS: The urologic
      malignancies included renal cell carcinoma (n = 13), prostate cancer (n = 5), and
      bladder transitional cell carcinoma (n = 3). The mean follow-up time was 10 +/-
      3.9 years. The mean age at diagnosis was 54 +/- 7.4 years and the mean time from
      transplantation was 4 +/- 3.3 years. The mortality rate among group was 19.0%.
      The analysis did not show significant differences in demographic or clinical
      characteristics between the groups, except for the prevalence of male gender and
      smoking status among the cancer cohort. No significant differences were observed
      for other suspected risk factors, including immunosuppressive protocols, time of
      pretransplantation dialysis, and age. CONCLUSIONS: The development of urologic
      malignancies is an early event, frequently observed within 4-5 years after
      transplantation. Therefore, this period should be considered for routine urologic
      cancer screening.

PMID- 22664002
TI  - Applicability of robot-assisted laparoscopic radical prostatectomy in renal
      allograft recipients.
AB  - PURPOSE: To evaluate the general applicability of robotic-assisted laparoscopic
      radical prostatectomy (RALP) in renal transplant recipients and potential
      surgical modifications due to the position of the transplanted kidney in the
      iliac fossa, as RALP has proven to be an effective and safe treatment option for
      prostate cancer (PCa) removal. PROCEDURES: A 71-year-old patient who had
      undergone renal transplantation was diagnosed with biopsy-proven localized
      Gleason 7a PCa. The prostate-specific antigen value was 12.4 ng/mL. RALP was
      performed by a transperitoneal approach using six ports. By partial mobilization
      of the bladder, the working space for the radical prostatectomy was created,
      while leaving the renal transplant and ureter untouched. Lymph node dissection
      was performed only on the contralateral side of the transplanted kidney. RESULTS:
      The procedure concluded after 220 minutes and the estimated blood loss was 300
      mL. The perioperative clinical course was uneventful. The kidney function
      remained normal with a creatinine value of 1.2 mg/dL. A complete extirpation of
      the prostate with negative surgical margins was achieved. After catheter removal,
      the patient was completely continent. CONCLUSIONS: RALP in renal transplant
      recipients is feasible and can be achieved with favorable oncological and
      functional outcome. No modifications to the standard RALP technique are required
      in these patients, except from a partial dissection of the bladder from the
      abdominal wall and a one-sided lymph node dissection.

PMID- 22664004
TI  - The Charlson comorbidity index as a predictor of outcomes in liver
      transplantation: single-center experience.
AB  - Several comorbidity indices, such as the Child-Turcotte-Pugh (CTP) score and the
      Model for End-Stage Liver Disease (MELD) score, have been used to optimize
      available organ resources and adjust priorities in diagnosis and allocation of
      grafts for patients who are candidates for liver transplantation. There have also
      been various attempts to create instruments to accurately predict outcomes after
      liver transplantation, but none has proved to be truly applicable, with the
      exception of the Charlson comorbidity index (CCI). We retrospectively reviewed
      data of 221 liver recipients, including living-related liver transplantation and
      multiple organ transplantation performed between January 2006 and September 2009.
      Survival analysis revealed a significant association of the CCI with decreased
      posttransplantation patient survival (P = .003). Furthermore, Kaplan-Meier plots
      and log-rank test showed a significant association between graft survival and the
      score (P = .039). Our data suggest that the CCI is a simple tool for the
      evaluation of comorbidity and that increased preoperative patient comorbidity
      increases the risk of graft loss and patient death after liver transplantation.
      The CCI should be considered an important tool for improving patient care because
      of its potential applications for patient management.

PMID- 22664005
TI  - Should a lower quality organ go to the least sick patient? Model for end-stage
      liver disease score and donor risk index as predictors of early allograft
      dysfunction.
AB  - BACKGROUND: There is a global tendency to justify transplanting extended criteria
      organs (ECD; Donor Risk Index [DRI] >= 1.7) into recipients with a lower Model
      for End-Stage Liver Disease (MELD) score and to transplant standard criteria
      organs (DRI < 1.7) into recipients with a higher MELD scores. There is a lack of
      evidence in the current literature to justify this assumption. METHODS: A review
      of our prospectively entered database for donation after brain death (DBD) liver
      transplantation (n = 310) between January 1, 2006, and September 30, 2010, was
      performed. DRI was dichotomized as <1.7 and >= 1.7. Recipients were divided into
      3 strata, those with high (>= 27), moderate (15-26), and low MELD (<15) scores.
      The recently validated definition of early allograft dysfunction (EAD) was used.
      We analyzed EAD and its relation with donor DRI and recipient MELD scores.
      RESULTS: The overall incidence of EAD was 24.5%. Mortality in the first 6 months
      in recipients with EAD was 20% compared with 3.4% for those without EAD (relative
      risk [RR], 5.56, 95% confidence interval [CI], 1.96-15.73; P < .001). Graft
      failure rate in the first 6 months in those with EAD was 27% compared with 5.8%
      for those without EAD (RR, 4.63; 95% CI, 2.02-10.6; P < .001). In patients with
      low MELD scores, a significantly increased rate of EAD (25%) was seen in patients
      transplanted with a high DRI liver compared with those transplanted with a low
      DRI liver (6.25%; P = .012). In moderate and high MELD recipients, there was no
      significant difference in the rate of EAD in patients transplanted with a high
      DRI liver (62%) compared with those transplanted with a low DRI liver (59%).
      CONCLUSION: These results suggest that contrary to common belief it is not
      justified to preferentially allocate organs with higher DRI to recipients with
      lower MELD scores.

PMID- 22664006
TI  - The association of promoter gene polymorphisms of the tumor necrosis factor-alpha
      and interleukin-10 with severity of lactic acidosis during liver transplantation
      surgery.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is a major operation, causing
      cytokine release and other inflammatory responses that can contribute to
      postreperfusion syndrome occurrence. During the systemic inflammatory response
      syndrome, increased lactate levels result from excessive cytokine production
      despite normal oxygen delivery and carbohydrate metabolism. The goal of the study
      was to determine the relationship between genetic polymorphisms in interleukin
      (IL)-10 (-1082G/A) or tumor necrosis factor (TNF)-alpha (-376 G/A) and lactate
      levels in patients during OLT surgery. PATIENTS AND METHODS: This prospective
      observational study in 40 consecutive adult patients who underwent OLT documented
      lactic acid levels at 5 times: Immediately after induction of anesthesia, at the
      end of the pre-anhepatic phase, at the end of the anhepatic phase, 1 hour after
      reperfusion, and at the end of surgery. Polymerase chain reaction (PCR; RFLP
      methodology) was used to examine IL-10 (-1082G/A) and TNF-alpha (-376 G/A) gene
      polymorphisms. RESULTS: Carriers of the IL-10/TNF-alpha genotype combination
      GG/GG showed significantly different changes in lactate levels at 1 hour after
      reperfusion and at the end of surgery. Lactate levels were significantly higher
      among patients heterozygous for TNF-alpha (AG genotype) compared with patients
      homozygous for TNF-alpha (GG genotype) at same times. In contrast, there was no
      significant difference among IL-10 polymorphic genotypes (-1082G/A). CONCLUSION:
      Genetic factors play a role in the development of lactic acidosis after OLT. IL
      10 (-1082G/A) and TNF-alpha (-376 G/A) gene polymorphisms could influence the
      variability of lactate levels after liver transplantation surgery.

PMID- 22664007
TI  - Perioperative use of continuous renal replacement therapy for orthotopic liver
      transplantation.
AB  - PURPOSE: We present a retrospective study describing the perioperative use of
      continuous renal replacement therapy (CRRT) for orthotopic liver transplantation
      (OLT). MATERIALS AND METHODS: We retrospectively reviewed the clinical course of
      patients who underwent OLT with the perioperative use of CRRT. The following
      variables were recorded: Gender, age, indication for transplantation, time when
      CRRT was initiated, postoperative need for CRRT, and the patient and organ
      (liver, kidneys) outcome up to 1 year after transplantation. RESULTS: Among 105
      patients who underwent OLT from 2006 to 2010; we used CRRT in 12 cases (11.4%)
      perioperatively, including 9 (8.3%) patients intraoperatively. Perioperative CRRT
      was employed for volume, electrolyte, and/or pH management. All patients who
      underwent CRRT perioperatively were alive at 1 month, 10 (83.3%), at 3 and 6
      months and 9 (75%) at 1 year after OLT. Only 1 surviving patient (8.3%) required
      renal replacement therapy at 1 month after surgery. Renal replacement therapy was
      not required in any surviving patient up to 12 months posttransplantation.
      CONCLUSION: Perioperative and especially intraoperative use of CRRT therapy can
      potentially improve the outcomes of patients undergoing OLT.

PMID- 22664008
TI  - Increased B-type natriuretic peptide during liver transplantation: relationship
      to invasively measured hemodynamic parameters.
AB  - BACKGROUND: The role of B-type natriuretic peptide (BNP) concentration in
      predicting cardiac dysfunction has been extensively investigated in many clinical
      conditions. Little is known, however, about its relationships with hemodynamic
      parameters from right heart catheterization in patients undergoing liver
      transplant surgery. METHODS: We retrospectively evaluated 525 patients who
      underwent liver transplantation. Hemodynamic variables from a Swan-Ganz catheter
      and BNP concentrations were measured 1 hour after induction of general
      anesthesia. Patients were stratified by quintiles of BNP concentrations.
      Univariate and multivariate logistic regression analysis were used to identify
      hemodynamic parameters associated with BNP >= 135 pg/mL, a cutoff point for the
      5th quintile. RESULTS: Univariate analysis showed that factors significantly
      associated with BNP >= 135 pg/mL included model for end-stage liver disease
      (MELD) score, diastolic blood pressure, mean pulmonary artery pressure, pulmonary
      capillary wedge pressure (PCWP), cardiac index, right ventricular end-diastolic
      volume index (RVEDVI), systemic vascular resistance index, pulmonary vascular
      resistance index (PVRI), and right ventricular stroke work index. Multivariate
      analysis revealed that MELD score (odds ratio [OR] = 1.059, P < .001), PCWP (OR =
      1.116, P = .026), RVEDVI (OR = 1.010, P = .009), and PVRI (OR = 1.009, P = .002)
      were independent determinants of BNP >= 135 pg/mL. CONCLUSIONS: Severity of liver
      disease, preload dependent hemodynamic parameters, and pulmonary vascular
      resistance were found to be significantly associated with increased BNP
      concentration, reinforcing the utility of BNP as a marker of cardiac strain and
      ventricular volume overload in liver failure patients undergoing liver transplant
      surgery.

PMID- 22664009
TI  - The impact of early corticosteroid withdrawal on graft survival in liver
      transplant recipients.
AB  - BACKGROUND: There has been increased interest in recent years in reducing or
      eliminating steroids from the immunosuppression regimen of transplant recipients
      to reduce adverse effects associated with their use. The purpose of this study
      was to compare clinical outcomes between early versus late steroid withdrawal
      after liver transplant to determine the optimal duration of steroid use in this
      population. METHODS: This large-scale, retrospective analysis of liver
      transplants occurred at our institution between 2000 and 2009. Patients were
      excluded if they were <18 years old, received a multiorgan transplant, or
      remained on steroids for >1 year. The early steroid withdrawal group had steroids
      eliminated by 3 months posttransplant; late steroid withdrawal patients had
      steroids withdrawn between 3 and 12 months posttransplant. RESULTS: A total of
      586 liver transplants occurred during the study period; 330 patients were
      included in the analysis. Graft survival was significantly lower in the early
      steroid withdrawal group. There was no difference in patient survival or overall
      acute rejection. However, the late steroid withdrawal group had a significantly
      higher rate of early acute rejection episodes. There was no difference with
      regard to new-onset diabetes after transplant, hyperlipidemia, or cardiovascular
      events between groups. CONCLUSION: The results of this study suggest that late
      corticosteroid withdrawal is associated with better long-term graft survival
      without increasing the rates of diabetes, hyperlipidemia, or cardiovascular
      events in liver transplant recipients. A prospective study is warranted to
      confirm these findings.

PMID- 22664010
TI  - Pharmacokinetics of mizoribine in adult living donor liver transplantation.
AB  - We investigated the pharmacokinetics of mizoribine in the acute phase after adult
      living donor liver transplantation (LDLT). Between February 2004 and October
      2009, 16 recipients received immunosuppressive therapy that included mizoribine
      (100 to 200 mg/d) after undergoing LDLT. We determined the serum levels of
      mizoribine before (C0) and 3 (C3), 4 (C4), and 10 (C10) hours after
      administration on postoperative days 3, 7, and 21. We assessed area under the
      concentration time curve (AUC) (hour . MUg/mL), normalized serum concentration
      (NSC) at C0 [concentration (MUg/mL)/dose (mg/kg body weight)], and estimated
      glomerular filtration rate (eGFR). The mizoribine concentration showed increases
      at C3 and C4 followed by a decrease at C10 on all days. AUC was 4.3, 5.9, and 8.3
      in the 200-mg/d dose group on days 3, 7, and 21, respectively. NSC at C0
      increased for 3 weeks after LDLT. There was a significant correlation between the
      NSC at C0 and eGFR on day 21, but not on days 3 and 7. There were no correlations
      between the NSC at C0 and either aspartate aminotransferase, total bilirubin,
      albumin, trough cyclosporine, or trough tacrolimus on any day. The
      pharmacokinetics of mizoribine in the acute phase after LDLT seems to be affected
      by postoperative day and renal function.

PMID- 22664011
TI  - Protein C activity and postoperative metabolic liver function after liver
      transplantation.
AB  - BACKGROUND: Protein C is a natural thrombin antagonist produced by hepatocytes.
      Its levels are low in liver failure and predispose patients to increased risk for
      thrombosis. Little is known about the relationship between protein C activity and
      hepatic function after orthotopic liver transplantation (OLT). METHODS: We
      measured protein C activity of 41 patients undergoing liver transplantation by
      the Staclot method (normal range, 70%-130%) preoperatively and then daily on
      postoperative days (POD) 0-5. RESULTS: The mean protein C activity was low before
      OLT (34.3 +/- 4.3%) and inversely correlated with the preoperative Model for End
      Stage Liver Disease score (Spearman's r = -0.643; P < .0001). Mean activity
      increased significantly on POD 1 (58.9 +/- 4.5%), and remained above preoperative
      levels through POD 5. Ten patients developed metabolic liver dysfunction defined
      by a serum total bilirubin >5 mg/dL on POD 7. These patients had significantly
      lower protein C activity from POD 3 (47.2 +/- 9.6% vs 75.9 +/- 5.8%; P = .01) to
      POD 5. Preoperative protein C activity correlated inversely with the severity of
      liver failure as indicated by preoperative MELD score. CONCLUSION: Protein C
      activity recovered rapidly in patients with good allograft function but remained
      significantly lower in patients who had limited metabolic function as evidenced
      by increased total bilirubin levels.

PMID- 22664012
TI  - Prediction of acute cellular rejection by peripheral blood eosinophilia in
      pediatric living donor liver transplantation.
AB  - BACKGROUND: Acute cellular rejection (ACR) is a common cause of morbidity
      following liver transplantation. Several reports have evaluated the predictive
      value of peripheral blood eosinophilia as a simple noninvasive diagnostic marker
      for ACR. This study examined whether the relative eosinophil counts (REC)
      predicted ACR in pediatric living donor liver transplantation (LDLT). METHODS:
      One hundred three patients underwent LDLT between May 2001 and December 2007. ACR
      were diagnosed based on the pathological findings. RESULTS: The incidence of ACR
      was 46.6% (48/103); ACR was diagnosed an average of 13.5 days after LDLT. The
      average REC at 4 and 2 days before the onset ACR (n = 39) within 30 postoperative
      day (POD) was 4.3% and 7.3%, respectively, and 9.0% at the onset. Patients with
      ACR showed significantly higher levels of REC compared with those free of ACR (P
      = .039). REC thresholds of 10% at POD 7 displayed a sensitivity and specificity
      of ACR detection of 80% and 75%, respectively. Moreover, the accumulated
      morbidity ratio of ACR within 30 POD was significantly higher with REC >10% at
      POD 7 (P = .007). CONCLUSION: ACR within POD 30 should be considered when REC is
      >10% at POD 7 after LDLT.

PMID- 22664013
TI  - Quality of life and physical activity in liver transplantation patients: results
      of a case-control study in Italy.
AB  - The aim of the study was to assess the quality of life (QOL) and the physical
      activity of liver transplant recipients compared with the general population. The
      case-controlled pilot study was accomplished through the administration of 2
      questionnaires: 36-item Medical Outcomes Study, Short-Form General Health Survey
      (SF-36) for quality of life (10 scores) and International Physical Activity
      Questionnaire (IPAQ) to estimate the physical activity (metabolic equivalent
      score). Fifty-four patients who underwent liver transplantation using the
      piggyback technique and 108 controls from the general population at the
      orthopedic ambulatories were enrolled between 2002 and 2009. Participants had a
      mean age of 55 years (range, 41-73). The multivariate analysis showed significant
      differences for some scales of the SF-36: liver transplant recipients displayed
      lower values for "Mental Composite Score" (P = .043), "physical activity" (P =
      .001), "role limitations due to physical health" (P = .006), "role limitations
      due to the emotional state" (P = .006), and "mental health" (P = .010). The
      metabolic equivalent positively associated with all examined SF-36 scales. The
      present study focused on the QOL and physical activity of liver transplant
      recipients, demonstrating that transplant recipients scored lower than the
      general population. Liver transplantation may allow full recovery of health
      status, but the physical and social problems persist in some patients.
      Interventions aimed at improving rehabilitation programs, regular psychosocial
      support, and follow-up in all phases of treatment may give patients a more
      satisfying lifestyle after transplantation.

PMID- 22664014
TI  - Routine induction therapy in living donor liver transplantation prevents
      rejection but may promote recurrence of hepatitis C.
AB  - BACKGROUND: Routine induction therapy in living donor liver transplantation
      (LDLT) has not been well described. METHODS: We reviewed outcomes of induction
      therapy with rabbit antithymocyte globulin (rATG) or basiliximab within 1 year of
      LDLT. RESULTS: Between 2002 and 2007, 184 adults underwent LDLT and received
      induction therapy in addition to standard immunosuppression. Acute cellular
      rejection (ACR) developed in 17 of 130 patients (13.1%) who received rATG and 13
      of 54 patients (24.1%) who received basiliximab (P = .066). The interval between
      transplantation and rejection as well as rejection severity was similar in
      patients who received rATG and those who received basiliximab. Hepatitis C (HCV)
      recurrence requiring initiation of antiviral therapy was more common in patients
      who received rATG compared with basiliximab (34.5% vs 8.7%; P = .021), and in
      those who received induction combined with tacrolimus as opposed to cyclosporine
      (38.5% vs 3.9%; P = .001). rATG and basiliximab were associated with excellent
      patient and graft survivals well as low rates of opportunistic infections and
      malignancies. CONCLUSION: Induction with rATG or basiliximab was well tolerated
      and highly effective at preventing ACR within 1 year of LDLT, but may be
      associated with a higher risk of clinically significant HCV recurrence in some
      patients.

PMID- 22664015
TI  - The value of pre-emptive therapy for cytomegalovirus after liver transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) infections are among the most common infections
      following liver transplantation. The main preventive methods for CMV infections
      are universal prophylaxis and pre-emptive therapy. In our study, we adopted a pre
      emptive strategy in a higth-risk group of donor CMV-positive (D+)/recipient CMV
      negative (R-) casses. We investigated whether this strategy was safe and
      effective to prevent CMV disease. METHODS: One hundred fifty-nine liver
      transplantation recipients who underwent over a 15-year period were
      retrospectively analyzed after follow-up for at least 6 months (mean, 63 months).
      Weekly quantitative polymerase chain reaction (PCR) measurements were performed
      to detect viral DNA. No CMV drug prophylaxis was given: antiviral CMV therapy was
      initiated when the PCR for CMV-DNA was >400 copies/mL. RESULTS: Fifty-one of 159
      liver transplant recipients enrolled in the study received antiviral therapy.
      High-risk patients (D+/R-) developed CMV infections significantly more often than
      D-/R- serostatus (P = .005). CMV disease was diagnosed in 12% of CMV-positive
      patients. Independent of serostatus in 14 cases (27.5%) virological recurrence of
      CMV infection occurred after primary treatment. Survival analysis showed no
      significant difference between patients with versus without CMV infection (P =
      .950). No relationship could be found between transplant rejection and CMV
      infection (P = .349). CONCLUSION: Our results showed that a pre-emptive strategy
      to prevent CMV disease was possible, even among the serological high-risk group.
      Only 12% of cases with CMV infection went on to manifest CMV disease with organ
      involvement. Survival curves were similar among patients with versus without CMV
      infections.

PMID- 22664016
TI  - Monthly ibandronate for the prevention of bone loss in patients after liver
      transplantation.
AB  - BACKGROUND: Osteopenia and osteoporosis are diseases frequently occurring after
      liver transplantation (OLT). PURPOSE: In a prospective study, we have
      investigated the effect of ibandronate, vitamin D(3), and calcium on the
      prevention and treatment of posttransplant osteopenia and osteoporosis. METHODS:
      The bone mineral density (BMD) of the lumbar spine (LS) and of the femoral neck
      (FN) were measured in 74 patients prospectively pre- and post-OLT. RESULTS:
      Postoperatively the study group showed a consistent percentage increase in BMD
      (g/cm(2)) and a significantly increased BMD after 12 and 24 months in the LS (12
      months: 1.05 +/- 0.21 g/cm(2); P < .001 24 months: 1.11 +/- 0.19 g/cm(2); P <
      .001) and the FN (12 months: 0.88 +/- 0.16 g/cm(2); P < .002 24 months: 0.90 +/-
      0.15 g/cm(2); P < .001) in comparison with baseline pre-OLT (LS pre-OLT 0.98 +/-
      0.19 g/cm(2), FN 0.86 +/- 0.14 g/cm(2)). The overall bone fracture rate was 5.4%
      up to 24 months. CONCLUSION: Ibandronate once monthly per os significantly
      increased the BMD in the LS and FN after OLT at 12 and 24 months. The increased
      BMD limits the risk of fracture.

PMID- 22664017
TI  - Vascular complications in hepatic transplantation: single-center experience in 14
      years.
AB  - PURPOSE: To evaluate the spectrum of liver transplantation-related vascular
      complications that occurred in a single center over the past 14 years. MATERIALS
      AND METHODS: Vascular complications and their clinical outcomes were reviewed
      among 744 liver transplant recipients. All patients underwent Doppler ultrasound
      with findings correlated with conventional or computed tomography angiography
      (CTA) in 111 patients. RESULTS: Among 70 recipients with vascular complications
      (%0.9), 14/26 patients with hepatic artery thrombosis underwent thrombectomy and
      arterial reanastomosis; six were retransplanted and six died. Among hepatic
      artery stenoses, three of nine were treated with balloon angioplasty and six
      underwent reanastomosis. Among 20 portal vein thromboses, 16 underwent
      thrombectomy, two patients retransplantation and two died. Seven patients with
      portal vein stenosis were followed. Two of six hepatic vein stenosis were
      restored with balloon angioplasty and three patients with metallic stent
      placement; the one other died. One patient with hepatic vein thrombosis died
      while the other patient was retransplanted. CONCLUSION: Transplantation related
      hepatic vascular complications diagnosed and managed in timely fashion showed a
      low mortality rate in our series.

PMID- 22664018
TI  - Vascular complications in pediatric liver transplantation; single-center
      experience from Singapore.
AB  - AIM: Vascular complications (VC) are a major cause of significant morbidity and
      mortality in pediatric liver transplantation (LT). We reviewed our series to
      study the evolution of vascular reconstructions and its effect on the incidence
      of VC after LT, particularly with regard to the portal vein (PV). METHODS: The
      medical records of 81 pediatric LT performed in 76 children (38 boys) from 1991
      to 2010 in the National University Hospital, Singapore, were reviewed to identify
      VC pertaining to PV, hepatic artery (HA), and hepatic veins (HV) and to analyse
      the data for the entire series and in 2 consecutive cohorts: initial 40 LT (group
      1) and subsequent 41 LT (group 2). Specific interventions in group 2 were
      characterized by surgical innovations for reconstruction of the difficult PV and
      routine use of Doppler ultrasound intraoperatively and postoperatively. RESULTS:
      The overall incidence of VC was 19.7% (n = 16) and individually HA thrombosis
      4.9% (n = 4), HA stenosis 1.2% (n = 1), PV thrombosis 12.3% (n = 9), PV stenosis
      1.2% (n = 1), and HV thrombosis 1.2% (n = 1). The overall 1- and 5-year survival
      rates in our series were 89% and 85%, respectively. The 1- and 5-year survival
      rates in patients with and without VC were 81.25% and 68.75% and 90.8% and 89.2%,
      respectively. The incidence of VC decreased from 27.5% in group 1 to 12.1% in
      group 2 (p = .08). The major contribution to this appears to be a decrease in PV
      complications from 17.5% in group 1 to 7.3% in group 2 (P = .1). The incidence of
      HA (3 vs 2) and HV (1 vs 0) complications was similar between the 2 groups.
      CONCLUSIONS: Vascular reconstructions in small recipients are technically
      challenging and associated with a learning curve. Application of meticulous
      techniques in general, surgical innovations to the difficult PV in particular and
      attention to postoperative monitoring contribute toward a major reduction in VC.

PMID- 22664019
TI  - Biliary strictures after orthotopic liver transplantation: long-term results of
      percutaneous treatment in patients with nonfeasible endoscopic therapy.
AB  - PURPOSE: The aim of this study was to evaluate our experience with percutaneous
      treatment of biliary strictures after orthotopic liver transplantation in adult
      patients without the endoscopic access possibility and to evaluate the technical
      outcomes and long-term clinical results of this treatment. MATERIALS AND METHODS:
      Thirty percutaneous procedures were performed in adult liver transplant
      recipients (13 men, 17 women, mean age 46.4 years) in our institution between
      1996 and 2010. Patients were treated with balloon dilatation and biliary duct
      drainage due to anastomotic stenosis (n = 20), nonanastomotic stenosis (n = 7),
      or due to stenosis caused by lymphoproliferation (n = 3). The percutaneous
      procedure was the first line of treatment due to hepaticojejunoanastomosis (n =
      18) or after unsuccessful endoscopic therapy (n = 12). RESULTS: Technical success
      was achieved in 27 patients (90%). The remaining three patients only achieved
      external drainage with subsequent surgery. There were two complications (6.3%).
      Long-term clinical success, defined as the absence of clinical, laboratory, or
      sonographic signs of stricture recurrence was achieved in 22 patients (73.3%) for
      a mean follow-up of 5.8 years. CONCLUSION: Percutaneous treatment--balloon
      dilatation and biliary duct drainage--is a first-line option to manage biliary
      duct strictures in liver recipient, when endoscopic treatment is not possible or
      unsuccessful. It has a high technical success rate and low complication rate with
      favorable long-term results.

PMID- 22664020
TI  - Impact of warm ischemia time on survival after heart transplantation.
AB  - BACKGROUND: There is little data available on the specific effects of warm
      ischemia time (WIT) as opposed to cold ischemia or storage time. With current
      research endeavors focusing on warm continuous perfusion, storage of donor
      hearts, and utilization of hearts from non-heart-beating donors, the impact of
      WIT on outcomes is increasingly relevant. The aim of this study was to analyze
      our results in cardiac transplantation with specific focus on the impact of WIT.
      METHODS: A retrospective review of 206 patients who underwent orthotopic heart
      transplantation at our institution between June 2001 and November 2010 was
      performed. Donor, recipient, and operative factors were analyzed. The main
      outcome variables were all cause mortality, survival, and primary graft failure.
      RESULTS: WIT of >80 minutes was associated with reduced survival compared with a
      shorter WIT of <60 minutes. Multivariate analysis showed increasing donor age to
      be the most significant variable associated with increased risk of mortality
      (hazard ratio 1.04; P = .004) per year of increasing donor age. CONCLUSIONS: This
      study has demonstrated a reduced survival in heart transplant recipients with
      increased WIT. This finding may be of particular relevance to potential future
      heart transplantation using organs procured from non-heart-beating donors.

PMID- 22664021
TI  - Peritoneovenous shunt for chylous ascites after lung transplantation for
      lymphangioleiomyomatosis.
AB  - A 37-year-old woman with lymphangioleiomyomatosis (LAM) who underwent right
      single-lung transplantation from a cadaveric donor developed persistent chylous
      ascites. Despite use of diuretics and sirolimus to reduce ascites-associated
      symptoms and to prevent gastroesophageal reflex triggered by increased abdominal
      pressure, the ascites were refractory, and periodic paracenteses were required.
      With placement of a peritoneovenous shunt (Denver shunt), the patient's abdominal
      circumference decreased, and her symptoms abated. Thus, placement of a
      peritoneovenous shunt can be an effective management strategy for refractory
      chylous ascites in patients with LAM, even after lung transplantation.

PMID- 22664022
TI  - A model of isolated, vascular whole thymus transplantation in nude rats.
AB  - BACKGROUND: We used a model of vascularized thymus lobes as a whole isolated
      organ transplantation in rats. MATERIALS AND METHODS: Male Fisher rats (F344,
      RT11v1; n = 10) and male homozygous Rowett nude rats (rnu/rnu; n = 10) were used
      as donors and recipients, respectively. Both vascular lobes of the thymus as a
      whole isolated organ were heterotopically transplanted to the neck of recipients.
      The right common carotid artery of the donor thymus was anastomosed end-to-end to
      the homonymous artery of the recipient. The anterior vena cava and the left
      brachiocephalic vein of the donor thymus were anastomosed end-to-side to the
      right and left external jugular veins of the recipient, respectively.
      Histological examination was used to monitor graft viability; graft function was
      assessed using flow cytometry (FCM) and immunologic effects by skin grafts in
      vivo. RESULTS: All recipients survived. Preparation of the donors and recipients
      took 35.6 +/- 5.5 minutes and 60.3 +/- 15.1 minutes, respectively. The blood
      supply to the thymus graft was patent. Histology of the thymus on postoperative
      days 14, 56, and 112 revealed viable grafts with preserved microarchitecture. FCM
      analysis showed 37.18 +/- 11.1% CD3+ T cells at day 21 after transplantation.
      Skin grafts from F344 and Rowett rats survived 8-10 and more than 30 days,
      respectively, whereas all third-party Sprague Dawley grafts were rejected within
      5 days. CONCLUSION: We developed a novel model of isolated, direct vascularized
      whole thymus transplantation in nude rats, in which both lobes of the fully
      vascularized thymus were harvested en bloc for successful transplantation.

PMID- 22664023
TI  - Transfusion of endothelial cells with lentivirus-mediated expression of fas
      ligand prolonged survival of rat liver allograft.
AB  - BACKGROUND: Immunologically privileged sites have been shown to express Fas
      ligand (FasL) and may protect themselves by inducing apoptosis of infiltrating
      inflammatory cells. We asked whether the Fas/FasL interaction could be used to
      protect liver allograft from acute rejection. We proposed that endothelial cells
      that are resistant to Fas-mediated killing could be considered as a vehicle for
      expression of recombinant FasL. METHODS: Based on the lenti-rFasl/puro expression
      system, constructs were designed that allowed endothelial cell-specific and
      continual expression of FasL. Endothelial cells with expression of FasL or
      viruses recombinant with FasL gene were transfused into portal vein of recipient
      rats during liver transplant surgery. Comparing groups of rats after liver
      transplant surgery using regular dose of FK506 and with no other treatment, we
      observed the aspartate aminotransferase and BIL value and survival of four groups
      of rat recipients. RESULTS: Values of AST and BIL in the cell and virus
      transfusion groups were between FK506 and contrast groups. The survival of cell
      and virus transfusion groups were longer than contrast group and shorter than
      FK506 group. CONCLUSION: This in vitro model shows that endothelial cells with
      expression of FasL or viruses recombinant with FasL gene transfusion can preserve
      liver function and prolong the survival time of liver allografts.

PMID- 22664024
TI  - High definition optical system for microsurgical heterotopic heart
      transplantation in rats.
AB  - BACKGROUND: Clinical and experimental cardiovascular surgery as well as other
      surgical disciplines may require visualization and manipulation of small anatomic
      structures. A high-definition optical system was developed for magnification and
      illumination as an alternative to surgical loupes or a traditional operating
      microscope. MATERIALS AND METHODS: A video telescopic optical imaging system that
      provided a high-definition and magnification of the surgical field was used for
      visualization of small anatomic structures and as an aid to the performance of
      small vessel anastomoses in a series of 10 heterotopic heart transplants (HHTx)
      in rats. RESULTS: The video telescopic optical system was easy to manipulate and
      comfortable to use, and provided high-definition images for magnification of
      anatomic structures while performing microvascular cardiac surgery in a small
      animal model of HHTx in rats. Fatigue and neck problems for the surgeon were
      reduced. CONCLUSIONS: The video telescopic imaging system provided high
      definition and magnification of the surgical field, and was used for
      visualization of small anatomic structures and as an aid to the performance of
      small vessel anastomoses. The system is an alternative to surgical loupes or a
      traditional operating microscope, and was used for the first time in
      microvascular cardiac surgery in a rat HHTx model.

PMID- 22664025
TI  - Cyclosporine induces up-regulation of immunoglobulin-like transcripts 3 and 4
      expression on and activity of NKL cells.
AB  - BACKGROUND: Immunoglobulin-like transcripts (ILTs), which belong to a kind of
      receptor family discovered recently, are differentially expressed on myeloid and
      lymphoid cells. Most of them play important roles to regulate human immune
      responses by interacting with ligands. Cyclosporine (CsA) is frequently used to
      prevent graft-versus-host disease and treat autoimmune diseases. There are some
      studies about the effects of CsA on various human immunologic reactions, but its
      impact on ILT3 and ILT4 expression on natural killer (NK) cells is less well
      understood. METHODS: An NKL cell line was exposed to CsA (5, 10, 15, or 20 mg/L)
      for 12, 24, or 36 hours before real-time quantitative polymerase chain reaction
      and flow cytometry were used to detect alterations in ILT3 and ILT4 mRNA and
      protein expressions. NKL cells treated for 36 hours with or without CsA (15 mg/L)
      and then coincubated with BGC-823 or JEG-3 cells, in cytolytic and proliferative
      systems measured by Thiazoyl blue tetrazolium bromide assays. RESULTS: After CsA
      treatment both RNA and protein levels of ILT3 and ILT4 on NKL cells were
      increased for 12, 24, or 36 hours. CsA at various concentrations inhibited the
      proliferation of NKL cells to varying degrees; at 36 hours CsA (15 mg/L) showed
      greater effects on ILT3 and ILT4 expression and less influence on NKL growth. The
      ability of NKL cells primed with CsA (15 mg/L) for 36 hours to kill tumor cells
      was decreased markedly. CONCLUSIONS: CsA up-regulated the expression of ILT3 and
      ILT4 on NKL cells, which influenced their cytotoxicity against tumor cells with
      different expression of HLA-G and proliferation of NKL cells.

PMID- 22664026
TI  - TH17 cells are critical for skin-specific pathological injury in acute graft
      versus-host disease.
AB  - Interleukin-17 (IL-17), which is important for host defens, has been implicated
      in autoimmune and chronic inflammatory diseases. As knockout mice lack IL-17
      expression in deltagammaT, NKT-like cells, studies investigating the association
      between TH17 cells and cutaneous graft-versus-host disease (GVHD) in animal
      models have reported conflicting results. To determine the role of TH17 cells in
      cutaneous GVHD, we developed an acute GVHD model using C57BL/6(H-2(b)) donors to
      BABL/c (H-2(d)) recipients. Blood samples and skin were examined for inflammation
      and infiltrating cells using histology and fluorescence-activated cell sorter
      (FACS) on days 6 and 15 after bone marrow transplantation. We found donor T cells
      to mediate severe cutaneous inflammation, which was ameliorater by administration
      of halofuginone (HF) to the recipients. Mechanistically, we demonstrate the
      severe tissue damage during this disorder to be associated with the production of
      IL-17 and the expansion of IL-17-producing CD4(+) cells. Specific inhibition of
      TH17 differentiation and function by HF reduced disease severity. Thus, TH17
      cells are sufficient to induce acute cutaneous GVHD.

PMID- 22664027
TI  - The expression and distribution of xenogeneic targeted antigens on porcine bone
      tissue.
AB  - OBJECTIVE: The objective of this study was to investigate the distribution of
      alpha-galactosyl (alpha-Gal), major histocompatibility complex (MHC)-I, and MHC
      II antigens on adult porcine bone tissue. METHODS: Distribution of alpha-Gal, MHC
      I, and MHC-II antigens on porcine bone tissue were observed using
      immunohistochemistry. RESULTS: alpha-Gal, MHC-I xenogeneic antigens were
      extensively observed on the surface of bone marrow cells, osteocytes,
      osteoblasts, and Harversian canals; MHC-II antigens were mainly expressed on bone
      marrow cells. CONCLUSION: alpha-Gal, MHC-I, and MHC-II are the main xenogeneic
      antigens that must be deleted to avoid xenogeneic immune reactions against bone
      xenografts.

PMID- 22664028
TI  - Decreasing loss of cryopreserved-thawed rat islets by coculture with Sertoli
      cells.
AB  - OBJECTIVE: Cryopreserved-thawed rat islets were cocultured with Sertoli cells to
      examine whether they could decrease the loss and improve islet function. METHODS:
      Islets and Sertoli cells were harvested from the pancreas and the testis of
      Sprague-Dawley rats, respectively. Cryopreserved, stored islets were thawed and
      divided into groups of coculture with Sertoli cells versus single cells. We
      measured islets recovery rate and function. Apoptotic-related proteins and gene
      expressions were detected by Western blot and reverse-transcriptase polymerase
      chain reaction. Soluble factors secreted by Sertoli cells in to the supernate
      were detected by enzyme-linked immunosorbent assay. We compared islet graft
      survival times in diabetic mice. RESULTS: In contrast to the single culture
      controls, thawed islets cocultured with Sertoli cells exhibited improved
      morphology. Recovery rates and insulin secretion were significantly higher among
      coculture cells. Four soluble factors were detected in supernates from Sertoli
      cell cultures including transforming growth factor-beta, insulin-like growth
      factor-1, epidermal growth factor, and basic fibroblast growth factor. Expression
      of proapoptotic Bax and caspase 3, 7 were down-regulated while that of
      antiapoptotic Bcl-2 was up-regulated. Cotransplantation with Sertoli cells
      significantly prolonged islet graft survival. CONCLUSION: These results suggested
      that coculture with Sertoli cells significantly improved islet yields and
      function after thawing and depressed islet apoptosis.

PMID- 22664029
TI  - Morphological and urodynamic evaluation of urinary bladder wall regeneration:
      muscles guarantee contraction but not proper function--a rat model research
      study.
AB  - BACKGROUND: Numerous studies are ungoing to develop a substitute for the native
      urinary bladder wall. The principals of tissue engineering approaches to urinary
      bladder wall augmentation require a favorable environment for smooth muscle
      regeneration, which is crucial for bladder function. This study was performed to
      evaluate bone marrow mesenchymal stem cells (BMSC) seeded on to amniotic
      membranes fixed to Tachosil sponges as grafts for urinary bladder muscle layer
      augmentation in a syngenic rat model. MATERIALS AND METHODS: Amniotic membranes
      seeded with BMSC and covered by Tachosil sponges were implanted as multilayer
      grafts into nine rats to regenerate the urinary bladder wall. The control group
      consisted of 12 healthy rats. Urodynamic examinations included contraction,
      elasticity, compliance, and urinary bladder motor activity. Hematocylin and eosin
      and Masson's trichrome stains were used to evaluate muscle regeneration;
      histological data were digitally analyzed with the ImageJ tool. RESULTS: The area
      of muscle bundles ranged from 5% to 25% or 32% to 41% in control versus
      reconstructed bladders, respectively. Among nine animals with reconstructed
      urinary bladders, urodynamic evaluation revealed bladder motor hyperactivity with
      regular (n = 4) or irregular (n = 1) storage and voiding phases, as well as
      proper bladder motor activity with a large bladder capacity (n = 1). No bladder
      contractility was recorded in one case and large stones developed in two animals,
      which made functional studies impossible. CONCLUSIONS: Regenerated smooth muscle
      cells created an autonomic cell population that was poorly assimilated to the
      rest of the urinary bladder wall. The histological presence of a regenerated
      muscle layer did not guarantee proper urinary bladder function.

PMID- 22664030
TI  - Effects of autologous bone marrow mononuclear cells implantation on
      cholangiocytes apoptosis in model of intrahepatic ischemic type biliary lesion in
      rabbits.
AB  - AIM: To investigate the effects of autologous bone marrow mononuclear cells (BM
      MNCs) implantation on regulation of cholangiocyte apoptosis in a model of
      intrahepatic ischemic type biliary lesion (ITBL) in rabbits. MATERIALS AND
      METHODS: Thirty Japanese white rabbits were divided randomly into 3 groups (10
      per group) including controls (group A), ITBL model (group B), and BM-MNCs
      implantation groups (group C). All rabbits underwent the same surgical procedure
      to prepare the liver for graft removal during transplantation. Subsequently, no
      additional vascular intervention was performed in group A. In group B, the
      hepatic artery and common bile duct were clamped with microvascular clips for 2
      hours, where after the clips were removed to recover the blood supply. Group C
      received, BM-MNCs (10(8) cells per rabbit) injected through the hepatic artery
      after removing the clips. The animals were killed 4 weeks after operation. The
      survival rate, histopathologic examination, cholangiocyte apoptosis with terminal
      uridine nick-end labeling (TUNEL) staining and expressions of Bcl-2 and Bax
      proteins were examined using immunohistochemical staining. RESULTS: Group A
      animals showed a survival of 100%; the rates in groups B and C were both 90%.
      Histopathologic examination revealed normal intrahepatic cholangiocytes in group
      A, obviously damaged ones in group B, and alleviated damage in group C. TUNEL
      staining indicated apoptosis of cholangiocytes in group B was more serious than
      that in group A or group C. Immunohistochemical staining demonstrated
      significantly decreased Bcl-2 expression in group B compared with that in group
      A; Bcl-2 expression in group C returned to the level of group A. Simultaneously,
      the Bax expression presented adverse results; the ratios of Bcl-2/Bax were ranked
      as group A > group C > group B. CONCLUSION: Implantation of autologous BM-MNCs
      significantly reduced apoptosis of intrahepatic cholangiocytes and prevented or
      abated intrahepatic ITBL.

PMID- 22664031
TI  - Urine is a highly cytotoxic agent: does it influence stem cell therapies in
      urology?
AB  - The state of art of stem cell therapies in urologic regenerative medicine is
      still under development. There are still many issues before advances in tissue
      engineering can be introduced for clinical application. The essential question is
      whether stem cells should be seeded on the urinary tract lumen side. The present
      experiment, using Real-Time Cell Analyzer (RTCA) DP (Dual Plate) of the
      xCellligence system (Roche Applied Science, Mannheim, Germany), allowed us to
      monitor cellular events in real time. In this study we examined the influence of
      urine on bone marrow-derived mesenchymal stem cells (MSC). Cells were exposed to
      medium mixed with urine (1:1), medium mix with PBS (Phosphate Buffered Saline)
      (1:1), only urine, and whole medium without cells as background. The cell number
      was significantly lower in all groups exposed on medium mixed with urine and
      urine alone. The results showed that urine is a highly cytotoxic agent whose role
      in urologic regenerative medicine is underestimated.

PMID- 22664032
TI  - Generation of donor-specific anti-human leukocyte antigen antibodies after the
      transplantation of a fully matched kidney allograft and its impact on the
      selection of a subsequent renal regraft: a case report.
AB  - Detection of anti-human leukocyte antigen (HLA) antibodies and identification of
      their specificities represent important tasks for patients awaiting kidney
      allografts. Regarding patients immunized by pregnancies, transfusions, or
      previous transplantations of solid organs, the immunization status must be
      observed carefully because grafting them with HLA phenotypes recognized by their
      antibodies represents the main cause for hyper-acute or acute rejection episodes,
      often leading to transplant loss. A 10-year-old patient with end-stage renal
      insufficiency of HLA type A3, 25; B8, 18, (Bw6); Cw7,12; DR15,17; DR51,52; DQ2,6
      received a deceased donor graft showing no HLA mismatch in 1998. It lost function
      after 8 years, resulting in the patient's re-entry onto the waiting list for
      kidney transplantation in 2006. Antibody screening detected anti-HLA-A25, A26,
      A34, and A66 (broad A10) antibodies using various techniques (DynaChip, Single
      Antigen enzyme-linked immunosorbent assay [ELISA]). Additionally, a kidney offer
      expressing the HLA-A25 phenotype was not acceptable for the patient due to a
      positive complement-dependent cytotoxicity assay (CDC)-based cross-match. The
      question arose whether this reactivity might be due to auto-reactive antibodies
      directed against the HLA-A25 phenotype. However, no auto-reactive antibodies were
      detectable using either the CDC-based or the antibody monitoring system-ELISA
      based cross-match assays. Consequently the patient was re-examined at high
      resolution showing the rare HLA-A*25:14 genotype. This case showed that rare
      alleles may result in allele-specific antibodies directed against the common
      variants, thus leading to unexpected positive cross-match results against
      apparently matched allografts.

PMID- 22664033
TI  - Renal vein extension using an autologous renal vein in a living donor with double
      inferior vena cava: a case report.
AB  - BACKGROUND: When the kidney from a living donor with a double inferior vena cava
      (IVC) is harvested for renal transplantation, the short length of the renal vein
      may eventually create a technical problem for graft implantation. Herein, we have
      reported a rare case of renal vein extension using an autologous renal vein in a
      living donor with a double IVC. CASE REPORT: A 70-year-old man with end-stage
      renal disease owing to autosomal-dominant polycystic kidney disease underwent a
      living donor kidney graft from his wife who had a double IVC. Because of the
      enlarged kidneys, the patient underwent a bilateral native nephrectomy with
      concomitant renal transplantation to create space in the pelvis. At nephrectomy,
      the recipient's renal vein was used to extend the donor renal vein. On the back
      table, the vein graft was sutured to the donor renal vein, permitting a 3.0-cm
      extension. RESULTS: The transplantation was performed safely without any
      complications; the recipient's renal function and blood flow were excellent after
      the operation. CONCLUSION: This case illustrated that an autologous renal vein
      graft is a preferable option to extend of short donor renal vein for recipients
      who require a simultaneous native nephrectomy.

PMID- 22664034
TI  - Complication arising from a duplicated inferior vena cava following laparoscopic
      living donor nephrectomy: a case report.
AB  - Selecting a kidney for living donor nephrectomy is driven by the tenet that
      donors are left with the higher functioning kidney. Traditionally, the left
      kidney is used because it has a longer renal vein, which aids anastamosis, and
      has an easier surgical approach. Anomalous left renal vasculature is not
      considered a contraindication to living donor nephrectomy. In the case of
      duplicated inferior vena cava, no specific considerations have been reported. We
      present a 42-year-old patient with infrarenal duplication of the vena cava who
      underwent laparoscopic living donor nephrectomy. His postoperative course was
      complicated by painful scrotal swelling necessitating multiple emergency room
      visits. Ultrasonography revealed bilateral hydroceles 5 weeks after surgery,
      which resolved with the use of a scrotal sling. Intraoperative ligation of a
      visibly dilated left gonadal vein was the likely etiology. Careful consideration
      should be taken in living donor nephrectomy in patients with duplication of
      inferior vena cava.

PMID- 22664035
TI  - Giant cavernous hemangioma in renal graft: a case report.
AB  - BACKGROUND: We present a case of giant cavernous hemangioma in renal graft tumor;
      we have not found any cases described in literature. CLINICAL CASE: Patient
      transplanted from a deceased donor, 8 years previous to her admission due to
      deterioration in renal function, observing a 12-cm renal mass in the front face
      of the renal graft, which displaces it, provoking obstructive uropathy. On
      ultrasonography and computed tomography, it is seen as a complicated, cystic
      lesion. Tumorectomy with a good functional recovery of the graft was carried out.
      A histopathologic study showed a mass with extensive adherences to the perirenal
      adipose tissue and a cross section showed a spongy appearance with blood clots in
      the centre, microscopically formed by vascular channels, lined by a layer of
      endothelial cells, and filled with blood. CONCLUSIONS: Giant cavernous hemangioma
      in renal graft tumor has not been previously described. Given its benign
      condition, nephron-sparing surgery should be carried out if possible.

PMID- 22664036
TI  - Acute liver failure due to Varicella zoster virus infection after lung
      transplantation: a case report.
AB  - Most adults are Varicella zoster virus (VZV)-positive at the age of 20 years.
      Some, however, remain antibody-negative and may develop primary chicken pox
      during adulthood. We report a patient with Williams-Campbell syndrome who
      underwent double-lung transplantation while being VZV-negative. One year after
      the successful procedure, he was admitted with fulminant hepatic failure and some
      cutaneous vesicles in his face. Despite a rapid diagnosis of VZV infection and
      treatment with acyclovir, his situation deteriorated within 24 hours and while
      awaiting an urgent liver transplantation, he developed multiple organ failure and
      died.

PMID- 22664037
TI  - Liver transplantation in a patient with developmental interruption of the
      inferior vena cava with azygos substitution.
AB  - Infrahepatic interruption of the inferior vena cava (IVC) with azygos or
      hemiazygos substitution has been reported frequently in children with biliary
      atresia where this venous abnormality is associated with other venous
      abnormalities such as preduodenal portal vein or congenital heart disease. It is
      important to recognize this anomaly pretransplant because the hepatic vein may
      drain directly into the right atrium rather than into the suprahepatic vena cava.
      We describe herein the first report of an orthotopic deceased donor liver
      transplant in an adult patient with an interrupted IVC and azygos continuation.
      We also review the embryological development of the IVC and the vascular
      anomalies that can occur.

PMID- 22664038
TI  - [Mesenteric hepatic portal pneumatosis: is it always an ominous diagnosis?].

PMID- 22664039
TI  - [Sacral root stimulation for untreatable anal pain].

PMID- 22664040
TI  - PTEN signaling in autism spectrum disorders.
AB  - PTEN germline mutations are found in a small subset of children diagnosed with
      autism spectrum disorder (ASD) and accompanying macrocephaly. In this review, we
      discuss recent advances that offer insight into the pathogenesis of this subgroup
      of autism patients. We provide an overview of how disrupting PTEN function
      influences neuronal cells, and describe efforts to decipher the cellular
      mechanisms associated with altered social behaviors. We discuss the PTEN
      downstream signaling pathways that likely mediate these cellular and behavioral
      effects. In addition, emerging data suggest that PTEN mutation can synergize with
      mutations in other autism susceptibility genes to contribute to the development
      of autistic behaviors. These studies extend our knowledge of PTEN and the PTEN
      signaling pathway, and offer molecular and cellular clues to better understand
      the etiology of ASDs.

PMID- 22664041
TI  - Pretreatment risk factors and importance of comorbidity for overall survival,
      complete remission, and early death in patients with acute myeloid leukemia.
AB  - The objective of this single-center study was to determine the pretreatment risk
      factors and influence of comorbidity on outcome in patients with acute myeloid
      leukemia (AML). The research involved 145 patients with AML during a 58-month
      follow-up period. The results suggest that the most significant predictor of poor
      overall survival (OS) is an adverse karyotype (P = 0.007), while for poor rate of
      complete remission (CR) it is age >=55 years, and for early death the most
      significant predictor is comorbidity, as scored by the Hematopoetic Cell
      Transplantation Comorbidity Index (HCT-CI), P = 0.001. When we divided the
      patients into two groups: aged >=55 years and aged <55 years, these predictors
      differed. In the group aged >=55 years the most significant predictor of OS (P =
      0.013) and for early death (P = 0.003) was HCT-CI (P = 0.013), while in the
      younger group it was karyotype (P < 0.001). The most significant predictor of CR
      in the elderly was increased serum lactate dehydrogenase (LDH) level (P = 0.045).
      In the younger patients, the most significant predictor of CR was leukocytosis (P
      = 0.001) and for early death it was infection as the comorbidity (P = 0.007). We
      point out the importance of comorbidity for OS and early death, as well as the
      impact of infection in patients with AML.

PMID- 22664043
TI  - CD20 expression in B-cell precursor acute lymphoblastic leukemia is common in
      Mexican patients and lacks a prognostic value.
AB  - Classification of acute lymphoblastic leukemia (ALL) by flow cytometric
      immunophenotyping characterizes the disease and delineates potential therapeutic
      intervention. We retrospectively analyzed CD20 expression in 143 patients with
      newly diagnosed precursor B-cell ALL. CD20 was observed in 61% of patients at
      diagnosis. There was no correlation between CD20 expression and age, white blood
      cell count, or cytogenetic abnormalities. Despite the fact that CD20-positive ALL
      patients had a tendency toward a worse outcome, there was no significant
      difference between patients with and without CD20 expression in 3-year overall
      survival 65 vs. 82% (P = 0.14), and cumulative incidence of relapse 36 vs. 18% (P
      = 0.3) in pediatric patients and 51 vs. 53% (P = 0.31) and 35 vs. 38% (P = 0.6)
      in adults, respectively. In conclusion, CD20 expression appears to be more common
      in Mexican patients with newly diagnosed precursor B-cell ALL higher than in
      Caucasian populations and lacks prognostic value.

PMID- 22664042
TI  - Evaluation of multidrug resistance in 46 newly diagnosed patients with acute
      leukemia.
AB  - OBJECTIVES: The aim of the present study was to assess the expression profile of
      multidrug resistance (MDR)-related proteins ABCB1, ABCC1 and LRP in 46 patients
      with acute leukemia (AL). METHODS: The levels of MDR gene mRNA expression and
      protein expression at diagnosis were analyzed by semi-quantitative PCR and flow
      cytometry, respectively. RESULTS: In the adult group, higher expression levels of
      abcc1 gene were associated with older age and lower levels of lactate
      dehydrogenase (LDH). In the pediatric group, abcc1 gene expression levels were
      associated with higher CD34 expression and a higher ABCB1 protein expression was
      correlated with high WBC counts. DISCUSSION/CONCLUSION: The present data indicate
      that abcb1 gene overexpression may be associated with a poor prognosis in adults
      with AL and that ABCB1 and abcc1 expression correlates with different prognostic
      factors in pediatric patients with AL. Our findings demonstrate that the method
      of choice to evaluate chemotherapy resistance-related proteins is a major
      variable.

PMID- 22664044
TI  - Expression feature of CD3, FcepsilonRIgamma, and Zap-70 in patients with chronic
      lymphocytic leukemia.
AB  - In leukemia patients, T-cell function has been suppressed with the disease
      progress. Patients with chronic lymphocytic leukemia (CLL) are all to a degree
      immunodeficient. In order to elucidate the feature of T-cell receptor signal
      transduction in CLL, the expression levels of CD3gamma, delta, epsilon, and zeta
      chain, FcepsilonRIgamma, and Zap-70 genes in peripheral blood mononuclear cells
      (PBMCs) were analyzed. Real-time polymerase chain reaction with SYBR Green
      technique was used for detecting the gene expression level in PBMCs from 13
      patients with CLL, 13 healthy individuals, and 10 B-cell acute lymphocytic
      leukemia (B-ALL) served as control. The beta2-microglobulin gene was used as an
      endogenous reference. Relative mRNA expression level of genes was analyzed by
      using the 2(-DeltaCt) * 100% method. Significant lower expression levels of
      CD3gamma, epsilon, and zeta chain genes, as well as FcepsilonRIgamma gene were
      found in CLL samples. Moreover, there was lost the negative correlation of the
      expression levels between CD3zeta and FcepsilonRIgamma genes. The expression
      level of Zap-70 in CLL was lower than those from healthy controls, while higher
      than those from B-ALL group. There was no significant correlation between the
      expression levels of CD3zeta and Zap-70 genes neither in the healthy group nor in
      the CLL group. In conclusion, the results provide a global gene expression
      profile of CD3gamma, delta, epsilon, and zeta chains, and the CD3zeta-related
      genes FcepsilonRIgamma and Zap-70 in CLL. Deficiency of these gene expression
      levels might represent the feature related to T-cell immunodeficiency. The study
      might contribute to better understand the cellular immune features in CLL
      patients.

PMID- 22664045
TI  - Value of 18FDG PET scan in staging of ocular adnexal lymphomas: a large single
      center experience.
AB  - Fluorine 18 deoxyglucose positron emission tomography ((18)FDG PET) is widely
      used in staging of non-Hodgkin's lymphomas (NHL), but very few studies have
      focused on its role in the initial staging of patients with ocular adnexal
      lymphoma (OAL). The aim of this study was therefore to evaluate the role of
      (18)FDG PET in the diagnosis of ophthalmologic lymphoma. A retrospective review
      of all imaging records, including computed tomography (CT), magnetic resonance
      imaging (MRI), and FDG PET, was performed. Forty-one OAL patients were included
      in the study. A pathologic review according to the World Health Organization
      classification showed 32 low-grade lymphoma patients (78%), including 26 mucosa
      associated lymphoid tissue lymphomas (63%). Ophthalmologic sites were intra
      orbital + lacrimal gland in 24 patients (59%), conjunctival in 13 patients (32%),
      multiple in 4 cases, and bilateral in 6 patients. (18)FDG PET was positive in
      orbital and conjunctival sites in 68 and 35% of cases, respectively. (18)FDG PET
      positivity was correlated with pathologic sites detected by MRI in 22/30 patients
      (73%); (18)FDG PET positivity was correlated with pathologic sites detected by CT
      in 25/34 patients (73%). This study shows that (18)FDG PET has a lower
      sensitivity than MRI to detect ophthalmologic lymphoma, particularly in non
      conjunctival sites.

PMID- 22664046
TI  - Moderate hyperprolactinemia is associated with survival in patients with acute
      graft-versus-host disease after allogeneic stem cell transplantation.
AB  - Fasting serum prolactin (PRL) levels in response to metoclopramide (MCP) and
      lymphocyte cytokine profiles was studied in patients given allografts and their
      donors. Thirty normoprolactinemic volunteers (12-59 years) were studied: group 1,
      10 healthy men; group 2, 8 males and 2 females with various hematologic diseases;
      and group 3, 3 males and 7 females HLA-identical sibling donors: PRL and
      cytokines were measured. Four surviving recipients developed acute graft-versus
      host disease (GVHD) (+), and six did not. Before transplant Fasting PRL
      concentrations were higher in 'future' GVHD(+) recipients than in their donors (P
      < 0.001). The opposite was seen in response to MCP (P = 0.01). Donors had a
      predominant T-helper type 1 (Th1) cytokine profile compared with recipients (P <=
      0.02), and GVHD(+) recipients had a greater tumor necrosis factor (TNF) value
      than GVHD(-) (P = 0.05). After transplant On days +30 and +100, a mild sustained
      rise in fasting PRL levels occurred only in GVHD(+) recipients (P <= 0.05)
      simultaneously with a transient rise in Th1 cytokines. GVHD(-) recipients had no
      changes. Donors with a Th1 cytokine profile might be more prone to induce GVHD in
      their recipients, and a mild sustained rise in PRL concentrations after
      transplantation in recipients GVHD(+) might participate in the amelioration of
      the severity of GVHD.

PMID- 22664047
TI  - Methylprednisolone induces apoptosis by interacting with the JAK/STAT pathway in
      HL-60 and K-562 leukemic cells.
AB  - OBJECTIVE: To determine the gene expression profiles of the JAK/STAT pathway
      members STAT3, STAT5A, STAT5B at both mRNA and protein levels in HL-60 and K-562
      leukemia cells that were undergoing apoptosis following high-dose
      methylprednisolone (MP) treatment. METHODS: HL-60 cells were treated with 0.1 mM
      MP and K-562 cells were treated with 0.4 mM MP according to their IC(50) values.
      STAT3, STAT5A, and STAT5B mRNA relative expression levels were determined by qRT
      PCR whereas the protein levels were detected via western-blot analysis and
      apoptosis was evaluated by Annexin V method. RESULTS: A significant decrease was
      seen in STAT5A mRNA relative expression level at 48 hours of MP treatment (P <
      0.05) both in HL-60 and K-562 cells. Other STATs showed a lower downregulation in
      their relative expressions at 48 hours at mRNA level for both of the cell lines.
      STAT proteins showed no expression change in K-562 cells in time course
      experiments but while STAT5A expression was downregulated; STAT5B showed an
      increase at 96 hours in HL-60 cells. Apoptosis was triggered by high-dose MP
      treatment that was evaluated by fluorescent microscopy. CONCLUSION: The JAK/STAT
      pathway components may play an important role in the apoptosis mechanism of
      leukemic cells under MP treatment in HL-60 and K-562 cells. Other pathways may
      also be involved with a post-translational modification seen in the HL-60 cell
      line, with both upregulation and downregulation of protein expression levels of
      STAT5B and STAT5A, respectively.

PMID- 22664048
TI  - Study of clinical and aetiological profile of 100 patients of pancytopenia at a
      tertiary care centre in India.
AB  - Pancytopenia is not a disease but an important clinico-haematological entity
      encountered in our day-to-day clinical practice with findings that may result
      from a number of disease processes. A total of 100 patients of pancytopenia
      admitted in medicine wards of Civil Hospital, Ahmedabad, Gujuarat, India, were
      studied. The most common cause of pancytopenia was megaloblastic anaemia (45%)
      followed by infections (20%) and hypersplenism (15%). As compared with other
      causes, megaloblastic anaemia was statistically significant cause (P < 0.01) of
      pancytopenia, in our study. The most common clinical presentation of patients
      with megaloblastic anaemia was lethargy (100%) and pallor (100%). In patients
      with megaloblastic anaemia, mean haemoglobin (Hb) was 5.6 +/- 1.7 g/dl, mean
      white blood corpuscle (WBC) count was 2735 +/- 4152 and mean platelet count was
      52,250 +/- 24,213. Mean corpuscular volume (MCV) was 101.2 +/- 11 in patients of
      megaloblastic anaemia. Morphology of RBC was marocytic in 95% of patients with
      megaloblastic anaemia, whereas hypersegmented neutrophils and macrovalocytes were
      seen in 60-65% patients of megaloblastic anaemia.

PMID- 22664049
TI  - Malaria: a haematological disease.
AB  - Plasmodium falciparum malaria remains a major cause of mortality throughout the
      tropical world. Haematological abnormalities are considered a hallmark of
      malaria, bearing an impact on final outcome and representing indices of
      prognostic and follow-up value. These include severe anaemia, coagulation
      disturbances, leukocyte numerical or functional changes and spleen involvement.
      Anaemia involves red blood cell lysis due to parasite invasion, as well as
      mechanisms of intravascular haemolysis and decreased erythropoiesis. Exchange or
      blood transfusion is mainly recommended in the management of these patients.
      Haemorrhagic complications in severe malaria are relatively rare despite
      prominent thrombocytopenia and dysfunction in the coagulation pathway. Numerical,
      as well as functional changes in the white blood cell are less dramatic than
      other blood cell series, but still, remain a significant index of disease
      progression and ultimate prognosis. Finally, the role of the spleen in severe
      malaria is multifactorial. Care and vigilance should be taken against splenic
      rupture which is fatal and can occur despite appropriate antimalarial prophylaxis
      and treatment.

PMID- 22664050
TI  - Thrombophilic gene mutations in children with migraine.
AB  - In 35 patients of both sexes (18 boys and 17 girls), mean age 8.9 +/- 4.5 years,
      affected by migraine both with (45.2%) and without an aura (54.9%) (P > 0.05) who
      had no alteration of brain computerized tomography and/or magnetic resonance
      imaging, we evaluated possible thrombotic events in the pathogenesis of the
      disease. In all cases and in 50 random healthy controls clotting tests
      (prothrombin time, activated partial thromboplastin time, protein C activity
      (PC), antithrombin III (ATIII), protein S (PS), antiphospholipid antibodies
      (aPL), and Lupus anticoagulant (LA) were normal. FVIII and FIX activities were
      increased in seven and five migraine sufferers, respectively. Genetic
      thrombophilic risk factors - factor V Leiden (FVL) and MTHFR677T - resulted in a
      significantly increased prevalence in migraine patients when compared with
      controls but without significant differences for the F2 polymorphism. The
      examined polymorphisms were associated with an increased risk of developing
      migraine (odds ratio (OR) > 1). These findings could confirm the key role of a
      reduced cerebral flow in the pathogenesis of migraine and possible risk of
      ischaemic stroke (IS) but we feel that these observations need to be confirmed in
      larger multi-centre studies.

PMID- 22664051
TI  - Effect of splenectomy on platelets associated antibodies in hepatitis C patients
      with thrombocytopenia.
AB  - BACKGROUND: This study aimed to assess the role of splenomegaly as a source of
      platelet-associated immunoglobulins (PAIgs) in thrombocytopenic patients with
      chronic hepatitis C virus (HCV) infection. SUBJECTS AND METHODS: The present
      study was conducted on 63 subjects categorized as follows. Group 1: Included 63
      cases diagnosed as patients with HCV liver cirrhosis combined with
      thrombocytopenia before splenectomy. Group 2: Included the same 63 cases one week
      after splenectomy. For all subjects included in this study platelets counts were
      evaluated as well as PAIgs (total Igs, IgG, IgM, and IgA). RESULTS: All patients
      were thrombocytopenic before undergoing splenectomy (platelet counts [median
      68.5; range 44-95]). After splenectomy all patients achieved normal platelet
      counts (median 180; range 108-235). The mean +/- SD of PAIgs was 64.2 +/- 9.6 for
      total IgG, 53.6 +/- 8.1 for IgG, 3.8 +/- 2.1 for IgM, 6.7 +/- 4.7 for IgA
      presplenectomy versus postsplenectomy 13.4 +/- 19.3 for total Igs, 5.4 +/- 1.8
      for IgG, 1.9 +/- 1.06 for IgM, 2.1 +/- 0.9 for IgA, and the differences between
      pre and postsplenectomy figures were statistically significant (P < 0.001). The
      correlation studies between platelet count and PAIgs level in patients with
      chronic HCV infection presplenectomy revealed that there is significant negative
      correlation between platelet counts and all immunoglobulins (total Igs: r -
      0.804, P = 0.000; IgG: r - 0.907, P = 0.000; IgM: r - 0.467, P = 0.002; and IgA:
      r - 0.519, P = 0.000). CONCLUSION: Autoimmune mechanism plays an important role
      in the HCV-associated thrombocytopenia and spleen is a major source of PAIgs.

PMID- 22664052
TI  - Comparative study of hypogonadism in beta-thalassemia intermedia patients with
      and without hydroxyurea.
AB  - BACKGROUND: We aimed at evaluating the effect of long-term use of hydroxyurea
      (HU) on gonad function in patients with beta-thalassemia intermedia (beta-TI) in
      Iran. METHODS: Seventy-five beta-TI patients aged >=11 years, mean serum ferritin
      level of <1000 ng/dL in the recent 5 years, and taking HU with a dose of 8-15 mg
      per kg body weight per day for at least 5 years were randomly selected during
      2010 in southern Iran. Thirty-one beta-TI patients without HU were considered as
      a control group. Serum levels of prolactin, luteinizing hormone, follicle
      stimulating hormone, testosterone, and estradiol were measured. An expert
      endocrinologist examined all participants and reviewed their hormonal profile.
      RESULTS: The mean age of the participants was 22.7 +/- 5.1 years (age range of 12
      41 years). Overall, 10 patients with hypogonadotropic hypogonadism were detected
      including seven patients (9.3%) with HU and three patients (9.7%) without HU. The
      difference between the two groups was not statistically significant (P = 0.605).
      CONCLUSION: It appears that long-term use of HU at a dose of 8-15 mg per kg body
      weight per day has no effect on gonad function in beta-TI patients. However,
      further prospective studies and large clinical trials are needed to confirm this
      subject.

PMID- 22664053
TI  - Predicting the likelihood of developing boar taint: early physical indicators in
      entire male pigs.
AB  - Three potential early-age predictors of which boars are likely to develop boar
      taint (testes volume, skin lesions and dirtiness) were measured on 102 boars
      every fortnight from 10 weeks of age until slaughter. These predictors were
      correlated with the level of boar taint according to the hot iron method and the
      concentrations of skatole and androstenone as determined by chemical analysis.
      The chance of no/low boar taint according to the hot iron method decreased with
      higher testes volume (weeks 22 and 24) and increased with skin lesion score
      (weeks 12, 16 and 18). For the concentrations of androstenone and skatole, the
      strongest correlation was found with testes volume in week 12. Skin lesions in
      week 16 were negatively correlated with skatole levels. Dirtiness was negatively
      correlated with skatole concentrations (week 18) but positively correlated with
      androstenone concentrations (weeks 20 and 22). Testes volume has the greatest
      potential for predicting the likelihood of developing boar taint.

PMID- 22664054
TI  - Liquid chromatography coupled to ion trap-tandem mass spectrometry to evaluate
      juvenile hormone III levels in bee hemolymph from Nosema spp. infected colonies.
AB  - It has been described a fast, simple and sensitive liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method to measure juvenile hormone III (JH III),
      which was used to study of the effects of Nosema spp. infection on JH III levels
      in bee hemolymph. Honey bee hemolymph was extracted by centrifugation and mixed
      with a solution of phenylthiourea in methanol. This mixture was then centrifuged
      and the supernatant removed and evaporated to dryness. The residue was
      reconstituted in methanol containing the internal standard (methoprene) and
      injected onto an LC-MS/MS (ion-trap) system coupled to electrospray ionization
      (ESI) in positive mode. Chromatography was performed on a Synergi Hydro-RP column
      (4 MUm, 30 mm * 4.60 mm i.d.) using a mobile phase of 20 mM ammonium formate and
      methanol in binary gradient elution mode. The method was fully validated and it
      was found to be selective, linear from 15 to 14,562 pg/MUL, precise and accurate,
      with %RSD values below 5%. The limits of detection and quantification were: LOD,
      6 pg/MUL; LOQ, 15 pg/MUL. Finally, the proposed LC-MS/MS method was used to
      analyze JH III levels in the hemolymph of worker honey bees (Apis mellifera
      iberiensis) experimentally infected with different Nosema spp. (Nosema apis,
      Spanish and Dutch Nosema ceranae strains). The highest concentrations of JH III
      were detected in hemolymph from bees infected with Spanish N. ceranae.

PMID- 22664055
TI  - Bile acid profiling in human biological samples: comparison of extraction
      procedures and application to normal and cholestatic patients.
AB  - The role of bile acids in cell metabolism, membrane biology and cell signaling is
      increasingly recognized, thus making necessary a robust and versatile technique
      to extract, separate and quantify a large concentration range of these numerous
      molecular species. HPLC-MS/MS analysis provides the highest sensitivity to detect
      and identify bile acids. However, due to their large chemical diversity,
      extraction methods are critical and quite difficult to optimize, as shown by a
      survey of the literature. This paper compares the performances of four bile acid
      extraction protocols applied to either liquid (serum, urine, bile) or solid
      (stool) samples. Acetonitrile was found to be the best solvent for deproteinizing
      liquid samples and NaOH the best one for stool extraction. These optimized
      extraction procedures allowed us to quantitate as much as 27 distinct bile acids
      including sulfated species in a unique 30 min HPLC run, including both
      hydrophilic and hydrophobic species with a high efficiency. Tandem MS provided a
      non ambiguous identification of each metabolite with a good sensitivity (LOQ
      below 20 nmol/l except for THDCA and TLCA). After validation, these methods,
      successfully applied to a group of 39 control patients, detected 14 different
      species in serum in the range of 30-800 nmol/l, 11 species in urine in the range
      of 20-200 nmol/l and 25 species in stool in the range of 0.4-2000 nmol/g. The
      clinical interest of this method has been then validated on cholestatic patients.
      The proposed protocols seem suitable for profiling bile acids in routine
      analysis.

PMID- 22664056
TI  - Click chemistry: a route to designing and preparing pseudo-biospecific
      immunoadsorbent for IgG adsorption.
AB  - L-histidine is a promising alternative to expensive protein ligands for the
      adsorption of IgG due to its high selectivity, no toxicity and low cost; while
      click chemistry can improve the reaction selectivity between the ligands and the
      support matrix under mild reaction conditions. Thus, using L-histidine as a
      ligand and original sepharose gel as a support, a novel immunoadsorbent
      possessing pseudo-biospecific affinity for IgG from human plasma, Sep-triazole
      His, was designed and prepared according to the principle of Click-reaction
      between alkyne and azide functional groups; while both sepharose-based control
      samples Sep-His and Sep-PA were prepared by a conventional method using L
      histidine and protein A as a ligand, respectively. The ligand density and IgG
      adsorption performance of Sep-triazole-His from human plasma were measured and
      evaluated. The influences of click chemistry on the preparation, structure and
      performance of sepharose-based immunoadsorbent were also investigated. The
      results indicate that the ligand density immobilized on Sep-triazole-His is 319.1
      MUmol/g sepharose gel, almost 4-fold as high as that on Sep-His; the IgG
      adsorption capacity of Sep-triazole-His from human plasma reaches 16.49 mg/g at
      pH 7.0, or increases 5.72-fold with respect to Sep-His, and does not decrease
      noticeably after being repeatedly used for 10 times; and Sep-triazole-His can
      exhibit high adsorption selectivity for IgG comparable to Sep-PA. The further
      studies prove that the 1,2,3-triazole ring in the spacer-arm of Sep-triazole-His,
      can facilitate the binding of IgG without non-specific adsorption.

PMID- 22664057
TI  - Biotransformation of flavonols and taxifolin in hepatocyte in vitro systems as
      determined by liquid chromatography with various stationary phases and
      electrospray ionization-quadrupole time-of-flight mass spectrometry.
AB  - Liquid chromatography (LC) on various stationary phases was used for the
      metabolite profile analysis of quercetin, rutin, isoquercitrin and taxifolin. The
      metabolites were obtained using an in vitro model system of human and rat
      hepatocytes in the form of cell suspensions and the primary cultures. For
      separations of the parent compounds and their metabolites, stationary phases
      based on C18, C8, cyanopropyl (CNP) or phenyl (PHE) modifications of silica were
      tested. CNP and PHE stationary phases operating in reversed-phase mode have been
      shown to be efficient for separation of parent flavonoids and their polar
      metabolites. Individual metabolites were identified on the basis of an elemental
      composition determination using electrospray ionization-quadrupole time-of-flight
      mass spectrometry (ESI-QqTOF MS) on-line connected with an LC system. Detailed
      analytical parameters such as retention times, selectivity, resolution of
      chromatographic peaks, MS fragmentation and UV-vis absorption maxima were
      determined for individual metabolites, namely for phase II biotransformation
      products. The predominant metabolites were methylated flavonols and flavonol
      glucuronides. The highest biotransformation rate was found with taxifolin, which
      was mainly converted to sulfates. The HPLC/ESI-QqTOF MS analyses revealed that
      quercetin and taxifolin were metabolized more extensively than the studied
      glycosides, rutin and isoquercitrin.

PMID- 22664058
TI  - Comparison of hemoglobin A1c measurements of samples with elevated fetal
      hemoglobin by three commercial assays.

PMID- 22664060
TI  - Incidence of metastasis in the circumflex iliac nodes distal to the external
      iliac nodes in ovarian cancer.
AB  - OBJECTIVE: The circumflex iliac nodes distal to the external iliac nodes
      (CINDEINs) are included in the regional lymph nodes that are commonly dissected
      during systematic lymphadenectomy for ovarian cancer. Because in recent years
      CINDEIN dissection has been reported as a significant risk factor for
      postoperative lower limb lymphedema, we investigated the validity of omitting the
      CINDEIN dissection by evaluating the distribution pattern of positive lymph nodes
      in ovarian cancer, in order to improve postoperative quality of life (QOL).
      METHODS: We performed a retrospective chart review of 142 patients with ovarian
      cancer who had undergone systematic lymphadenectomy between 1995 and 2010. We
      assessed the distribution pattern of lymph node metastasis and the presence of
      CINDEIN metastasis according to the pT classification (pT1, pT2, and pT3).
      RESULTS: Of the 142 patients, 71, 21, and 50 were classified into pT1, pT2, and
      pT3, respectively. The lymph nodes most frequently involved were the para-aortic
      lymph nodes superior to the mesenteric artery (14%), followed by the obturator
      nodes (11%), the internal iliac nodes (9.4%), and the common iliac nodes (7.4%).
      Although the frequency of CINDEIN metastasis was 5.3% (6 of 114 cases with
      CINDEIN dissection), no metastasis to the CINDEINs was observed in pT1 patients.
      CONCLUSIONS: It may be acceptable to omit CINDEIN dissection during surgery for
      pT1 ovarian cancer in view of postoperative QOL.

PMID- 22664059
TI  - A phase 2 trial of flavopiridol (Alvocidib) and cisplatin in platin-resistant
      ovarian and primary peritoneal carcinoma: MC0261.
AB  - PURPOSE: Based upon promising preclinical and phase 1 trial results, combined
      flavopiridol and cisplatin therapy was evaluated in patients with ovarian and
      primary peritoneal cancers. METHODS: A two cohort phase 2 trial of cisplatin (60
      mg/m2 IV) immediately followed by flavopiridol (100 mg/m2 IV, 24 h infusion; 21
      day cycles) was undertaken in patients with recurrent platin-sensitive or platin
      resistant disease (progression>vs. <=6 months following prior platin-based
      therapy). Measurable disease (RECIST)--or evaluable disease plus CA125>2X post
      treatment nadir--and ECOG performance<=2 were required. RESULTS: Forty-five
      patients were enrolled between December 23, 2004 and February 25, 2010: 40 platin
      resistant (Group 1), and 5 platin-sensitive (Group 2). In Group 1, the median
      number of treatment cycles was 3 (range 2-12). Only 10% of patients incurred
      grade 4 toxicities, but grade 3 toxicities were common (65%): neutropenia
      (17.5%); nausea (12.5%); vomiting, fatigue, thrombosis, anemia (10% each). Seven
      patients (17.5%) achieved a confirmed response (1 CR, 6 PR; median duration 118
      days); ten additional patients (25%) attained maintained stable disease. Median
      time to progression was 4.3 months; overall survival was 16.1 months. Pilot
      translational studies assessed ascites flavopiridol level; surrogate marker
      studies were uninformative. In Group 2, although 4 of 5 patients responded (2
      confirmed PRs with median time to progression, 10.8 months and median overall
      survival 20.6 months) the cohort was closed due to poor accrual. CONCLUSIONS: The
      assessed flavopiridol and cisplatin regimen displayed clinical activity in platin
      resistant and sensitive ovarian/primary peritoneal cancers, meriting further
      study.

PMID- 22664061
TI  - Phylogenetics of the Old World screwworm fly and its significance for planning
      control and monitoring invasions in Asia.
AB  - Phylogenetic, genealogical and population relationships of Chrysomya bezziana,
      the Old World screwworm fly (OWSF), were inferred from DNA sequences of
      mitochondrial cytochrome b (cyt b), nuclear elongation factor-1alpha (EF-1alpha)
      and nuclear white eye colour (white), using sequences of Chrysomya megacephala
      and Chrysomya rufifacies as outgroups. Cyt b (717bp, 754 specimens), EF-1alpha
      (361bp, 256 specimens) and white (577bp, 242 specimens) were analysed from up to
      two African and nine Asian countries, including 10 Indonesian islands. We show
      that OWSF occurs as distinctive African and Asian lineages based on cyt b and
      white, and that there is a marked differentiation between Sumatran and Javan
      populations in Indonesia, supported by the genealogy and analysis of molecular
      variance of cyt b alone. Four cyt b sub-lineages are recognised in Asia: only 2.1
      occurs on the Asian mainland, from Yemen to Peninsular Malaysia; only 2.2, 2.3
      and 2.4 occur in central Indonesia; 2.4 predominates on New Guinea; and 2.1 co
      occurs with others only on Sumatra in western Indonesia. This phylogeography and
      the genetic distances between cyt b haplotypes indicate pre-historic, natural
      dispersal of OWSF eastwards into Indonesia and other Malesian islands, followed
      by vicariant evolution in New Guinea and central Indonesia. OWSF is absent from
      Australia, where there is surveillance for importation or natural invasion.
      Judged by cyt b haplotype markers, there is currently little spread of OWSF
      across sea barriers, despite frequent shipments of Australian livestock through
      Indonesian seas to the Middle East Gulf region. These findings will inform plans
      for integrated pest management, which could be applied progressively, for example
      starting in East Nusa Tenggara (central Indonesia) where OWSF has regional cyt b
      markers, and progressing westwards to Java where any invasion from Sumatra is
      unlikely. Cyt b markers would help identify the source of any re-emergence in
      treated areas.

PMID- 22664062
TI  - Mechanism for translocation of fluoroquinolones across lipid membranes.
AB  - Classical atom-scale molecular dynamics simulations, constrained free energy
      calculations, and quantum mechanical (QM) calculations are employed to study the
      diffusive translocation of ciprofloxacin (CPFX) across lipid membranes. CPFX is
      considered here as a representative of the fluoroquinolone antibiotics class.
      Neutral and zwitterionic CPFX coexist at physiological pH, with the latter being
      predominant. Simulations reveal that only the neutral form permeates the bilayer,
      and it does so through a novel mechanism that involves dissolution of concerted
      stacks of zwitterionic ciprofloxacins. Subsequent QM analysis of the observed
      molecular stacking shows the important role of partial charge neutralization in
      the stacks, highlighting how the zwitterionic form of the drug is neutralized for
      translocation. The findings propose a translocation mechanism in which
      zwitterionic CPFX molecules approach the membrane in stacks, but they diffuse
      through the membrane as neutral CPFX monomers due to intermolecular transfer of
      protons favored by partial solvation loss. The mechanism is expected to be of
      importance in the permeation and translocation of a variety of ampholitic drugs
      with stacking tendencies.

PMID- 22664063
TI  - Reorganization of lipid domain distribution in giant unilamellar vesicles upon
      immobilization with different membrane tethers.
AB  - Characterization of phase coexistence in biologically relevant lipid mixtures is
      often carried out through confocal microscopy of giant unilamellar lipid vesicles
      (GUVs), loaded with fluorescent membrane probes. This last analysis is generally
      limited to the vesicle hemisphere further away from the coverslip, in order to
      avoid artifacts induced by the interaction with the solid surface, and
      immobilization of vesicles is in many cases required in order to carry out
      intensity, lifetime or single-molecule based microscopy. This is generally
      achieved through the use of membrane tethers adhering to a coverslip surface.
      Here, we aimed to determine whether GUV immobilization through membrane tethers
      induces changes in lipid domain distribution within liposomes displaying
      coexistence of lipid lamellar phases. Confocal imaging and a Forster resonance
      energy transfer (FRET) methodology showed that biotinylated phospholipids present
      significantly different membrane phase partition behavior upon protein binding,
      depending on the presence or absence of a linker between the lipid headgroup and
      the biotinyl moiety. Membrane phases enriched in a membrane tether displayed in
      some cases a dramatically increased affinity for the immobilization surface,
      effectively driving sorting of lipid domains to the adherent membrane area, and
      in some cases complete sequestering of a lipid phase to the interaction surface
      was observed. On the light of these results, we conclude that tethering of lipid
      membranes to protein surfaces has the potential to drastically reorganize the
      distribution of lipid domains, and this reorganization is solely dictated by the
      partition properties of the protein-tether complex.

PMID- 22664064
TI  - Determinants of persistent spread of HIV in HCV-infected populations of injecting
      drug users.
AB  - Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are both
      transmitted through populations of injecting drug users (IDU) by the sharing of
      contaminated syringes. Prevalence of HCV is high in most IDU populations, whereas
      HIV prevalence varies considerably across populations. Understanding the dynamics
      of these interacting infections may allow us to use HCV prevalence as an
      indicator for the risk of persistent spread of HIV. We developed a mathematical
      model that describes the spread of both HCV and HIV in an IDU population. The
      model allows for HCV-HIV co-infection and increased disease related mortality for
      both infections. Using this model we investigated how HIV and HCV prevalence both
      depend on level and heterogeneity of injecting risk behaviour, and how HIV and
      HCV prevalence are related. To gain knowledge of actual risk behaviour we
      analysed data from the Amsterdam Cohort Study (ACS) of drug users. We find that
      there is a threshold HCV prevalence at which HIV can invade into an IDU
      population; below threshold HIV cannot spread. This threshold depends strongly on
      heterogeneity of risk behaviour in the population, as well as on whether sharing
      is more likely to occur within or between risk behaviour groups. We find that our
      model agrees with the observed relationship between HCV and HIV prevalence as
      described by Vickerman et al. (2010), when in addition to risk heterogeneity as
      fitted from the ACS, we also assume that most contacts (>90%) occur amongst IDU
      of the same risk level (assortative mixing). We conclude that HCV prevalence can
      be used as an indicator of risk for successful HIV introduction into an IDU
      population. However, information on risk heterogeneity is required for
      determining this risk, and also for designing effective prevention strategies.

PMID- 22664065
TI  - An improved regulatory sampling method for mapping and representing plant disease
      from a limited number of samples.
AB  - A key challenge for plant pathologists is to develop efficient methods to
      describe spatial patterns of disease spread accurately from a limited number of
      samples. Knowledge of disease spread is essential for informing and justifying
      plant disease management measures. A mechanistic modelling approach is adopted
      for disease mapping which is based on disease dispersal gradients and
      consideration of host pattern. The method is extended to provide measures of
      uncertainty for the estimates of disease at each host location. In addition,
      improvements have been made to increase computational efficiency by better
      initialising the disease status of unsampled hosts and speeding up the
      optimisation process of the model parameters. These improvements facilitate the
      practical use of the method by providing information on: (a) mechanisms of
      pathogen dispersal, (b) distance and pattern of disease spread, and (c)
      prediction of infection probabilities for unsampled hosts. Two data sets of
      disease observations, Huanglongbing (HLB) of citrus and strawberry powdery
      mildew, were used to evaluate the performance of the new method for disease
      mapping. The result showed that our method gave better estimates of precision for
      unsampled hosts, compared to both the original method and spatial interpolation.
      This enables decision makers to understand the spatial aspects of disease
      processes, and thus formulate regulatory actions accordingly to enhance disease
      control.

PMID- 22664066
TI  - Optimal but unequitable prophylactic distribution of vaccine.
AB  - The final epidemic size (R(infinity)) remains one of the fundamental outcomes of
      an epidemic, and measures the total number of individuals infected during a "free
      fall" epidemic when no additional control action is taken. As such, it provides
      an idealised measure for optimising control policies before an epidemic arises.
      Although the generality of formulae for calculating the final epidemic size have
      been discussed previously, we offer an alternative probabilistic argument and
      then use this formula to consider the optimal deployment of vaccine in spatially
      segregated populations that minimises the total number of cases. We show that for
      a limited stockpile of vaccine, the optimal policy is often to immunise one
      population to the exclusion of others. However, as greater realism is included,
      this extreme and arguably unethical policy, is replaced by an optimal strategy
      where vaccine supply is more evenly spatially distributed.

PMID- 22664067
TI  - Transmission dynamics of hepatitis E virus in pigs: estimation from field data
      and effect of vaccination.
AB  - Hepatitis E is a viral disease that causes serious concerns for public health.
      Hepatitis E virus (HEV) genotype 3 is endemic in commercial pig farms worldwide
      that act as a reservoir. Pig-to-human transmission may occur when infectious
      animals enter the food chain at slaughter, through consumption of contaminated
      meat, direct exposure or use of by-products. To reduce the fraction of infectious
      animals at slaughter age and thus the risk for public health, it is important to
      understand the transmission dynamics of HEV in pig populations. In this study, we
      estimate the transmission rate parameter and mean infectious period of HEV in
      pigs from field data, using a Bayesian analysis. The data were collected in ten
      commercial pig herds that are each divided into three different age groups. Two
      transmission models were compared, assuming that animals are infected either
      locally by their group mates or globally by any infectious animal regardless of
      its group. For local and global transmission, the transmission rate parameters
      were 0.11 (posterior median with 95% credible interval: 0.092-0.14 day(-1)) and
      0.16 (0.082-0.29 day(-1)), the mean infectious periods were 24 (18-33) days and
      27 (20-39) days and the reproduction numbers were 2.7 (2.2-3.6) and 4.3 (2.8
      6.9). Based on these results, global transmission is considered to be the more
      conservative model. Three effects of vaccination were explored separately. When
      vaccination is not sufficient to eliminate the virus, a shorter mean infectious
      period decreases the fraction of infectious animals at slaughter age, whereas a
      reduced transmission rate parameter adversely increases it. With a reduced
      susceptibility, vaccination of animals at a later age can be a better strategy
      than early vaccination. These effects should be taken into account in vaccine
      development.

PMID- 22664068
TI  - Modelling the within-host dynamics of the foot-and-mouth disease virus in cattle.
AB  - In this paper we investigate the within-host dynamics of the foot-and-mouth
      disease virus (FMDV) in cattle using previously published data for 8
      experimentally infected cows. An 8-compartment, 14-parameter differential
      equation model was fitted to data collected from each cow every 24 h over the
      course of an infection on: (i) the concentration of FMDV genomes in the blood,
      (ii) the concentration of infectious virus in the blood, (iii) antibody levels,
      and (iv) interferon levels. Model parameters were estimated using maximum
      likelihood methods. The likelihood surface was sampled using Markov chain Monte
      Carlo methods giving credible intervals for each of the model parameters. The
      model was able to capture the within-host dynamics well for 6 of the infections,
      with both the innate (type 1 interferon) and antibody responses playing key roles
      in determining the height and duration of peak levels of virus. There was
      considerable variation between virus dynamics in individual cattle which was only
      partly accounted for by inferred differences in the dose of virus received. A
      better understanding of the within-host dynamics also provides insights into the
      dynamics of infectiousness and the transmission of virus to new hosts.

PMID- 22664070
TI  - Editorial: novel strategies for the design of therapeutic antimicrobial peptides.

PMID- 22664071
TI  - Antimicrobial peptide action on parasites.
AB  - Diseases caused by protozoan parasites can pose a severe thread to human health
      and are behind some serious neglected tropical diseases like malaria and
      leishmaniasis. Though several different drugs have been developed in order to
      eradicate these diseases, a successful candidate has not yet been discovered.
      Among the most active compounds tested, antimicrobial peptides (AMPs) are
      particularly appealing because of their wide spectrum of action. AMPs have been
      described to perturb protozoan homeostasis by disrupting the cellular membranes
      but also by interfering with key processes in the parasite metabolism. In this
      review we describe the diverse mechanisms of action of AMPs on protozoan targets
      and how they can be exploited to treat diseases. Moreover, we describe with
      detail the antimicrobial action of AMPs on two major parasitical infections:
      leishmaniasis and malaria. All the features reviewed here show that AMPs are
      promising drugs to target protozoan parasites and that further understanding of
      the mechanism of action of these compounds will lead to improved drugs that could
      be worth to test in a clinical phase.

PMID- 22664069
TI  - Agent-based and phylogenetic analyses reveal how HIV-1 moves between risk groups:
      injecting drug users sustain the heterosexual epidemic in Latvia.
AB  - Injecting drug users (IDUs) are a driving force for the spread of HIV-1 in Latvia
      and other Baltic States, accounting for a majority of cases. However, in recent
      years, heterosexual cases have increased disproportionately. It is unclear how
      the changes in incidence patterns in Latvia can be explained, and how important
      IDUs are for the heterosexual sub-epidemic. We introduce a novel epidemic model
      and use phylogenetic analyses in parallel to examine the spread of HIV-1 in
      Latvia between 1987 and 2010. Using a hybrid framework with a mean-field
      description for the susceptible population and an agent-based model for the
      infecteds, we track infected individuals and follow transmission histories
      dynamically formed during the simulation. The agent-based simulations and the
      phylogenetic analysis show that more than half of the heterosexual transmissions
      in Latvia were caused by IDU, which sustain the heterosexual epidemic. Indeed, we
      find that heterosexual clusters are characterized by short transmission chains
      with up to 63% of the chains dying out after the first introduction. In the
      simulations, the distribution of transmission chain sizes follows a power law
      distribution, which is confirmed by the phylogenetic data. Our models indicate
      that frequent introductions reduced the extinction probability of an autonomously
      spreading heterosexual HIV-1 epidemic, which now has the potential to dominate
      the spread of the overall epidemic in the future. Furthermore, our model shows
      that social heterogeneity of the susceptible population can explain the shift in
      HIV-1 incidence in Latvia over the course of the epidemic. Thus, the decrease in
      IDU incidence may be due to local heterogeneities in transmission, rather than
      the implementation of control measures. Increases in susceptibles, through social
      or geographic movement of IDU, could lead to a boost in HIV-1 infections in this
      risk group. Targeting individuals that bridge social groups would help prevent
      further spread of the epidemic.

PMID- 22664073
TI  - Bacterial cell wall compounds as promising targets of antimicrobial agents II.
      Immunological and clinical aspects.
AB  - The bacterial cell wall represents the primary target for antimicrobial agents.
      Microbial destruction is accompanied by the release of potent immunostimulatory
      membrane constituents. Both Gram-positive and Gram-negative bacteria release a
      variety of lipoproteins and peptidoglycan fragments. Gram-positive bacteria
      additionally provide lipoteichoic acids, whereas Gram-negative bacteria also
      release lipopolysaccharide (LPS, endotoxin), essential component of the outer
      leaflet of the bacterial cell wall and one of the most potent immunostimulatory
      molecules known. Immune activation therefore can be considered as an adverse
      effect of antimicrobial destruction and killing during anti-infective treatment.
      In contrast to antibiotics, the use of cationic amphiphilic antimicrobial
      peptides allows both effective bacterial killing and inhibition of the
      immunostimulatory effect of the released bacterial membrane constituents. The
      administration of antimicrobial peptides alone or in combination with antibiotic
      agents thus represents a novel strategy in the antiinfective treatment with
      potentially important beneficial aspects. Here, data are presented which describe
      immunological and clinical aspects of the use of antimicrobial peptides (AMPs) as
      therapeutic agents to treat bacterial infection and neutralize the
      immunostimulatory activity of released cell wall constituents.

PMID- 22664072
TI  - Bacterial cell wall compounds as promising targets of antimicrobial agents I.
      Antimicrobial peptides and lipopolyamines.
AB  - The first barrier that an antimicrobial agent must overcome when interacting with
      its target is the microbial cell wall. In the case of Gram-negative bacteria,
      additional to the cytoplasmic membrane and the peptidoglycan layer, an outer
      membrane (OM) is the outermost barrier. The OM has an asymmetric distribution of
      the lipids with phospholipids and lipopolysaccharide (LPS) located in the inner
      and outer leaflets, respectively. In contrast, Gram-positive bacteria lack OM and
      possess a much thicker peptidoglycan layer compared to their Gram-negative
      counterparts. An additional class of amphiphiles exists in Gram-positives, the
      lipoteichoic acids (LTA), which may represent important structural components.
      These long molecules cross-bridge the entire cell envelope with their lipid
      component inserting into the outer leaflet of the cytoplasmic membrane and the
      teichoic acid portion penetrating into the peptidoglycan layer. Furthermore, both
      classes of bacteria have other important amphiphiles, such as lipoproteins, whose
      importance has become evident only recently. It is not known yet whether any of
      these amphiphilic components are able to stimulate the immune system under
      physiological conditions as constituents of intact bacteria. However, all of them
      have a very high pro-inflammatory activity when released from the cell. Such a
      release may take place through the interaction with the immune system, or with
      antibiotics (particularly with those targeting cell wall components), or simply
      by the bacterial division. Therefore, a given antimicrobial agent must ideally
      have a double character, namely, it must overcome the bacterial cell wall
      barrier, without inducing the liberation of the pro-inflammatory amphiphiles.
      Here, new data are presented which describe the development and use of membrane
      active antimicrobial agents, in particular antimicrobial peptides (AMPs) and
      lipopolyamines. In this way, essential progress was achieved, in particular with
      respect to the inhibition of deleterious consequences of bacterial infections
      such as severe sepsis and septic shock.

PMID- 22664074
TI  - Antimicrobial peptide delivery strategies: use of recombinant antimicrobial
      peptides in paratransgenic control systems.
AB  - Antimicrobial peptides (AMP's) are small peptides that have evolved as part of an
      innate cell defense mechanism in many organisms. We are currently developing
      methodologies to use these molecules to control the transmission of vector borne
      diseases utilizing a paratransgenic strategy. In this approach, symbiotic or
      commensal microbes of host insects are transformed to express gene products that
      interfere with pathogen transmission. These genetically altered microbes are re
      introduced back to the insect where expression of the engineered molecules
      decreases the host's ability to transmit the pathogen. In previous work, we
      demonstrated that the paratransgenic expression of the AMP, cecropin A, by
      transformed microbes residing in the midgut of the reduviid bug, reduced carriage
      of the parasite, T. cruzi, substantially. In more recent work, we reported a
      dramatic increase in parasite killing efficiency when AMP's are used in
      combination. Further, the AMP concentrations required for parasite killing are
      decreased by at least 10-fold. In this review, we discuss the feasibility of
      utilizing other AMP's, individually or in combination, as effector molecules to
      control the transmission of leishmania parasites by sand flies and to control
      Vibriosis, a highly devastating disease in shrimp mariculture.

PMID- 22664075
TI  - Nanotools for the delivery of antimicrobial peptides.
AB  - Antimicrobial peptide drugs are increasingly attractive therapeutic agents as
      their roles in physiopathological processes are being unraveled and because the
      development of recombinant DNA technology has made them economically affordable
      in large amounts and high purity. However, due to lack of specificity regarding
      the target cells, difficulty in attaining them, or reduced half-lives, most
      current administration methods require high doses. On the other hand, reduced
      specificity of toxic drugs demands low concentrations to minimize undesirable
      side-effects, thus incurring the risk of having sublethal amounts which favour
      the appearance of resistant microbial strains. In this scenario, targeted
      delivery can fulfill the objective of achieving the intake of total quantities
      sufficiently low to be innocuous for the patient but that locally are high enough
      to be lethal for the infectious agent. One of the major advances in recent years
      has been the size reduction of drug carriers that have dimensions in the
      nanometer scale and thus are much smaller than -and capable of being internalized
      by- many types of cells. Among the different types of potential antimicrobial
      peptide-encapsulating structures reviewed here are liposomes, dendritic polymers,
      solid core nanoparticles, carbon nanotubes, and DNA cages. These nanoparticulate
      systems can be functionalized with a plethora of biomolecules providing
      specificity of binding to particular cell types or locations; as examples of
      these targeting elements we will present antibodies, DNA aptamers, cell
      penetrating peptides, and carbohydrates. Multifunctional Trojan horse-like
      nanovessels can be engineered by choosing the adequate peptide content,
      encapsulating structure, and targeting moiety for each particular application.

PMID- 22664076
TI  - Discovering new in silico tools for antimicrobial peptide prediction.
AB  - Antimicrobial peptides (AMPs) are important effectors of the innate immune system
      and play a vital role in the prevention of infections. Due to the increased
      emergence of new antibiotic-resistant bacteria, new drugs are constantly under
      investigation. AMPs in particular are recognized as promising candidates because
      of their modularity and wide antimicrobial spectrum. However, the mechanisms of
      action of AMPs, as well as their structure-activity relationships, are not
      completely understood. AMPs display no conserved three-dimensional structure and
      poor sequence conservation, which hinders rational design. Several bioinformatics
      tools have been developed to generate new templates with appealing antimicrobial
      properties with the aim of finding highly active peptide compounds with low
      cytotoxicity. The current tools reviewed here allow for the prediction and design
      of new active peptides with reasonable accuracy. However, a reliable method to
      assess the antimicrobial activity of AMPs has not yet been developed. The
      standardization of procedures to experimentally evaluate the antimicrobial
      activity of AMPs, together with the constant growth of current well-established
      databases, may allow for the future development of new bioinformatics tools to
      accurately predict antimicrobial activity.

PMID- 22664077
TI  - Editorial. Imaging inflammatory bowel disease: looking beyond the mucosa.

PMID- 22664078
TI  - Ultrasound in Crohn's disease.
AB  - Over the past few years, the technical evolution of ultrasound equipment, the use
      of oral and intravenous contrast agents, and an increase in the expertise of
      sonographers has enhanced the role of ultrasonography that plays in the
      assessment of the gastrointestinal tract. In chronic inflammatory conditions,
      primarily CD, this technology can be used not only for diagnostic purposes, but
      it has also been suggested that it could play a role in the management of the
      disease.

PMID- 22664079
TI  - Imaging in inflammatory bowel disease mucosal healing in ulcerative colitis:
      relevance for clinical outcomes.
AB  - There is growing evidence of the importance of mucosal healing (MH) in ulcerative
      colitis, but whether or not it should be a future primary treatment goal is still
      under intense discussion. Within the last decade many clinical trials have
      focused not only on response and remission rates but also on achievement of MH,
      while in clinical practice we still make treatment decisions on the basis of
      clinical symptoms. There is so far no internationally accepted definition of MH
      and the tools for assessment of MH vary from biomarkers to endoscopy with
      histological evaluation on the basis of several different scores and indices.
      This review will focus on present data dealing with methods to assess MH and the
      importance of MH for the future course of disease, the need for colectomy or risk
      of developing colorectal cancer and the patient's quality of life. Many questions
      remain: How and when do we best assess MH? How rapidly do we need to achieve MH?
      What is the optimal time point to discontinue treatment after achieving MH? Well
      defined prospective studies are needed to address these important questions.

PMID- 22664080
TI  - Can radiology replace endoscopy in IBD?
AB  - Inflammatory bowel disease diagnostic and management algorithms continue to
      rapidly evolve. This is partly driven by advanced radiologic techniques that
      provide objective, non-invasive evaluations. The realms of information provided
      by radiology and endoscopy continue to be intertwined. This has led to the
      question of whether radiologic applications will continue to expand, and
      eventually replace endoscopy in inflammatory bowel disease assessments. The
      likely outcome, however, will not be replacement, but rather imaging tools that
      complement endoscopic evaluations to provide global disease damage and activity
      scores.

PMID- 22664081
TI  - Mucosal healing in Crohn's disease: relevance for clinical outcomes.
AB  - The clinical management of Crohn's disease (CD) has evolved in recent years from
      symptom control to healing of mucosal lesions. Mucosal healing, induced and
      maintained by immunomodulators and/or biologicals, has been shown to alter the
      disease course in patients with CD. As a consequence, long-term disease outcomes
      have been dramatically improved, in particular since the introduction of anti
      tumor necrosis factor (TNF) agents. CD patients with active inflammation
      (ileocolonic ulcers and/or increased C-reactive protein levels) benefit most from
      treatment with TNF antagonists. Since healing of the inflamed mucosa is now
      considered an important treatment goal, endoscopic monitoring is gradually
      entering routine practice. Therefore, the mucosal appearance will more and more
      influence the therapeutic decision making process. Mucosal healing has also
      become an end-point in therapeutic trials. We will summarize some of the
      fundamental issues regarding mucosal healing and discuss data to support its
      clinical relevance in the management of CD.

PMID- 22664082
TI  - Imaging of the colon in inflammatory bowel disease: ready for prime time?
AB  - Endoscopy is currently considered the reference standard for the evaluation of
      disease activity and severity in patients with inflammatory bowel disease (IBD).
      However, information provided by endoscopy is limited to the mucosal surface and
      cannot always be complete. Cross-sectional imaging techniques are gaining
      acceptance for the assessment of patients with Crohn's disease (CD) and
      ulcerative colitis (UC). Overall diagnostic accuracy of ultrasonography (US),
      computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation
      of colonic lesions in patients with IBD is high. The main limitation of US is its
      high dependence on expertise of the examiner and the anatomic location of
      lesions, and its main strengths are wide availability safety and low cost. CT is
      highly accurate for the evaluation of patients with IBD, but due to safety issues
      related to radiation exposure this technique should be reserved for urgent
      situations in which US is not diagnostic. Technological advances in the area of
      MRI have allowed optimization for the assessment of patients with IBD, mainly CD.
      Available evidence suggests that magnetic resonance colonography (MRC) has a high
      diagnostic accuracy for the detection of disease activity, location, severity,
      and complications, particularly for penetrating and stricturing lesions,
      characteristic of CD. MRC can provide a valuable guidance for performing medical
      and surgical treatment with maximized efficacy and safety. Overall, MRI findings
      accurately reflect disease activity and provide reliable information for decision
      making and patient care optimization.

PMID- 22664083
TI  - Capsule endoscopy in Crohn's disease.
AB  - Capsule endoscopy (CE) represents a significant advance in the investigation of
      small bowel diseases. Two-thirds of Crohn's disease (CD) patients have small
      bowel involvement at diagnosis. Study of small intestine mucosa by CE may have a
      strong impact on CD management in a near future. CE may be superior to small
      bowel cross-sectional imaging for detection of mucosal lesions consistent with CD
      and a normal CE has a high negative predictive value for active small bowel CD. A
      GI imaging study should generally precede CE to rule out complications such as
      fistulas and strictures. In established CD, CE may be useful in patients with
      unexplained symptoms when other investigations are inconclusive, if this will
      alter management. The low specificity of CE is its main drawback. Furthermore,
      there are no validated CD diagnosis criteria for CE and no severity indexes have
      been independently validated. The role of CE in evaluating mucosal healing and
      postoperative recurrence will require additional investigation.

PMID- 22664084
TI  - Unveiling cancer in IBD: screening colonoscopy or chromoendoscopy.
AB  - The risk of developing colorectal cancer (CRC) is increased in patients with
      inflammatory bowel disease (IBD), particularly if the disease is extensive and
      its duration long-standing. Endoscopic guidelines have been developed with the
      goal of detecting early neoplastic changes prior to development of advanced
      malignancy. The current surveillance strategy of surveillance colonoscopy, with
      multiple random biopsies, most likely reduces morbidity and mortality associated
      with IBD-related CRC. Unfortunately, standard surveillance colonoscopy also has
      limitations, including high cost and sampling error at time of biopsy. The main
      issue is that colitis associated neoplasms often occur in flat mucosa of normal
      appearance, and are detected on taking random biopsies rather than by direct
      identification of these lesions via endoscopic imaging. Advances in endoscopic
      imaging techniques, such as vital or optical chromoendoscopy, that can enhance
      mucosal characteristics, may potentially aid in increasing dysplasia detection
      rate, and may reduce the workload of standard random biopsies. The aim of this
      review was to describe and summarize outcomes of more advanced endoscopic imaging
      techniques, including chromoendoscopy and magnification endoscopy.

PMID- 22664085
TI  - The role of magnetic resonance imaging in detecting intestinal fibrosis in
      Crohn's disease.
AB  - One of the main challenges for clinicians dealing with Crohn's disease (CD) is to
      distinguish between inflammation and fibrosis, two sequential steps in the
      evolution of the intestinal disease. While inflammation is amenable to medical
      treatment, stricturing disease can only benefit from surgery. Magnetic resonance
      imaging (MRI) is a widely used tool in the diagnosis and assessment of CD. Recent
      data suggest that this technique might help in discriminating between fibrosis
      and inflammation and as such potentially guide medical decisions. In this review
      we will first highlight the main diagnostic techniques for CD. We will then
      briefly review the main mechanisms of fibrosis in this condition and the use of
      MRI in CD focusing on findings predictive of fibrosis and fibrotic evolution.

PMID- 22664086
TI  - Imaging modalities for perianal Crohn's disease.
AB  - Anorectal involvement in Crohn's disease (CD) causes perianal lesions that vary
      from simple asymptomatic skin tags, to complex disabling fistulas and abscesses.
      Perianal CD affects approximately one-third of patients; its management is
      challenging and may require combined medical and surgical treatment, which has
      proven to offer the best chance of success. An optimal preoperative disease
      assessment is crucial in order to achieve an optimal outcome and avoid
      irreversible damage due to incomplete or inaccurate intervention. Imaging
      modalities are useful in order to confirm diagnosis, to accurately classify the
      disease, as to plan the most suitable treatment and monitor its results.
      Endoscopic Ultrasonography (EUS) and pelvic Magnetic Resonance (MRI) represent
      the best options from this perspective, both in terms of sensitivity and
      specificity, as well as for their demonstrated role in influencing treatment
      approach. Transperineal Ultrasonography (TPUS) may be helpful when EUS is
      contraindicated or not-tolerated. Computed Tomography (CT) and fistulography are
      generally no longer considered due to their inferior performance and the
      radiation exposure they involve. All imaging should be done in conjunction with
      an Evaluation Under Anesthesia (EUA) performed by an expert surgeon, to ensure
      accurate disease assessment. In this paper we review available data on each
      imaging modality, comparing performance and focusing on specific pros and cons,
      in order to assist clinicians in choosing the most appropriate treatment option
      for each individual patient.

PMID- 22664087
TI  - Medical therapy and mucosal healing.
AB  - In ulcerative colitis, mucosal healing has clearly been incorporated in the
      assessment of treatment efficacy. In Crohn's disease, this concept has only
      emerged in recent clinical trials with biological therapies. Systemic steroids
      don't reliably induce mucosal healing in Crohn's disease, but purine analogues
      and anti-TNF agents have a potential to heal mucosal ulcerations. Evidence for
      mucosal healing has now been provided for the anti-TNF agents infliximab,
      adalimumab and certolizumab pegol. For infliximab in Crohn's disease, mucosal
      healing has been associated with a reduction in clinical relapses, disease
      related hospitalizations and surgeries. On the contrary, the benefit of treating
      asymptomatic patients with IBD more intensively until they achieve mucosal
      healing has not been proven. In clinical practice, assessing mucosal healing
      should be considered in patients with persistent symptoms despite adequate
      therapy as well as in patients where treatment discontinuation is being
      considered.

PMID- 22664088
TI  - Establishment of the Australian infectious diseases research centre.

PMID- 22664089
TI  - Targeting quorum sensing and competence stimulation for antimicrobial
      chemotherapy.
AB  - Bacterial resistance to antibiotics is now a serious problem, with traditional
      classes of antibiotics having gradually become ineffective. New drugs are
      therefore needed to target and inhibit novel pathways that affect the growth of
      bacteria. An important feature in the survival of bacteria is that they
      coordinate their efforts together as a colony via secreted auto-inducing
      molecules. Competence stimulating peptides (CSPs) are among the quorum sensing
      pheromones involved in this coordination. These peptides activate a two-component
      system in gram-negative bacteria, binding to and activating a histidine kinase
      receptor called ComD, which phosphorylates a response regulator called ComE,
      leading to gene expression and induction of competence. Competent bacteria are
      able to take up exogenous DNA and incorporate it into their own genome. By this
      mechanism bacteria are able to acquire and share genes encoding antibiotic
      resistance. Despite having been studied for over 30 years, this pathway has only
      recently begun to be explored as a novel approach to modulating bacterial growth.
      Antagonists of ComD might block the signaling cascade that leads to competence,
      while overstimulation of ComD might also reduce bacterial growth. One possible
      approach to inhibiting ComD is to examine peptide sequences of CSPs that activate
      ComD and attempt to constrain them to bioactive conformations, likely to have
      higher affinity due to pre-organization for recognition by the receptor. Thus,
      small molecules that mimic an alpha helical epitope of CSPs, the putative ComD
      binding domain, have been shown here to inhibit growth of bacteria such as S.
      pneumoniae. Such alpha helix mimetics may be valuable clues to antibacterial
      chemotherapeutic agents that utilize a new mechanism to control bacterial growth.

PMID- 22664090
TI  - Adaptors in toll-like receptor signaling and their potential as therapeutic
      targets.
AB  - To initiate the innate immune response, Toll-like receptors (TLRs) associate with
      cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain
      interactions. The four principal signaling adaptor proteins include MyD88, MAL,
      TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR
      pathways, is usually considered a part of the TIR domain-containing adaptor
      protein group. Other TIR domain-containing proteins have also been shown to
      regulate these signaling pathways, including ST2 and SIGIRR, as well as several
      bacterial and viral TIR domain-containing proteins that modulate these pathways
      as virulence factors. TLR pathways and the adaptor proteins are associated with a
      number of diseases, including infection, sepsis, inflammatory, allergic and
      autoimmune diseases and cancer. We review our current understanding of the
      structure and function of adaptor proteins and their regulatory proteins, their
      association with disease and their potential as therapeutic targets in human
      disease.

PMID- 22664091
TI  - Resolving biofilm infections: current therapy and drug discovery strategies.
AB  - Biofilms formed by pathogenic bacteria present a serious threat to human health
      as the efficacy of standard antibiotic therapeutic regimens is compromised by
      reduced microbial susceptibility within the biofilm environment. The discovery of
      improved therapies for biofilm elimination requires an understanding of biofilm
      formation and dispersal, and the development of assays to specifically analyze
      these dynamic processes. This review will discuss biofilm screening strategies
      suitable for drug discovery efforts, especially chemical and biological
      approaches that specifically target biofilm destruction.

PMID- 22664092
TI  - Uropathogenic Escherichia coli mediated urinary tract infection.
AB  - Urinary tract infection (UTI) is among the most common infectious diseases of
      humans and is the most common nosocomial infection in the developed world. They
      cause significant morbidity and mortality, with approximately 150 million cases
      globally per year. It is estimated that 40-50% of women and 5% of men will
      develop a UTI in their lifetime, and UTI accounts for more than 1 million
      hospitalizations and $1.6 billion in medical expenses each year in the USA.
      Uropathogenic E. coli (UPEC) is the primary cause of UTI. This review presents an
      overview of the primary virulence factors of UPEC, the major host responses to
      infection of the urinary tract, the emergence of specific multidrug resistant
      clones of UPEC, antibiotic treatment options for UPEC-mediated UTI and the
      current state of vaccine strategies as well as other novel anti-adhesive and
      prophylactic approaches to prevent UTI. New and emerging themes in UPEC research
      are also discussed in the context of future outlooks.

PMID- 22664093
TI  - Prokaryotic substrate-binding proteins as targets for antimicrobial therapies.
AB  - The rapid emergence of multidrug-resistant bacteria over the last two decades has
      catalyzed a shift away from traditional antibiotic development strategies and
      encouraged the search for unconventional drug targets. Prokaryotic substrate-
      binding proteins (SBPs), together with their cognate ATP-binding cassette (ABC)
      transporters, facilitate the unidirectional, transbilayer movement of specific
      extracytosolic cargoes against a concentration gradient, powered by ATP
      hydrolysis. In Gram-negative bacteria, SBPs are found in the periplasmic space,
      whereas in Gram-positive organisms these proteins are anchored to the outer cell
      wall by a lipid moiety. SBPs are vital components of the substrate-translocation
      machinery, as they determine cargo specificity and are involved in coupling the
      cargo uptake process with ABC transporter- mediated ATP hydrolysis. In this
      review, we focus on "Cluster A-1" divalent metal-binding proteins from within the
      SBP family. Acquisition of transition row metal ions is essential for bacterial
      colonization and virulence and Cluster A-1 SBPs play an integral role in this
      process. Cluster A-1 SBPs lack homologs in humans, bypass the need to deliver
      compounds into the bacterial cell, and are therefore potential drug targets
      against Gram-positive bacteria. Here we discuss the role SBPs play in the
      prokaryotic substrate-translocation machinery with emphasis in the substrate
      binding mechanism of Cluster A-1 SBPs, the role of these proteins in virulence
      and their potential use as drug targets.

PMID- 22664094
TI  - RNA interference for viral infections.
AB  - The treatment of viral infections has relied on pre-emptive vaccination or use of
      a limited range of anti-viral drugs. However, the majority of viruses have no
      available drugs and treatment is merely supportive. RNA interference (RNAi)
      offers the ability to directly and rapidly treat virus infections via the
      targeting of viral genes. Indeed, clinical trials have already been undertaken
      with promising results. Here we review the current state of the RNAi field for
      the treatment of viral infections such as HIV, human papillomavirus and HCV. We
      also review novel strategies including the concept of targeting self-genes to
      limit viral infection and activating the immune system for improved outcomes.
      Finally we examine innovative approaches being pursued at the Australian
      Infectious Diseases Research Centre including the use of high-throughput siRNA
      screens to identify new antiviral targets.

PMID- 22664095
TI  - Wzy-dependent bacterial capsules as potential drug targets.
AB  - The bacterial capsule is a recognized virulence factor in pathogenic bacteria. It
      likely works as an antiphagocytic barrier by minimizing complement deposition on
      the bacterial surface. With the continual rise of bacterial pathogens resistant
      to multiple antibiotics, there is an increasing need for novel drugs. In the Wzy
      dependent pathway, the biosynthesis of capsular polysaccharide (CPS) is regulated
      by a phosphoregulatory system, whose main components consist of bacterial
      tyrosine kinases (BY-kinases) and their cognate phosphatases. The ability to
      regulate capsule biosynthesis has been shown to be vital for pathogenicity,
      because different stages of infection require a shift in capsule thickness,
      making the phosphoregulatory proteins suitable as drug targets. Here, we review
      the role of regulatory proteins focusing on Streptococcus pneumoniae,
      Staphylococcus aureus, and Escherichia coli and discuss their suitability as
      targets in structure-based drug design.

PMID- 22664097
TI  - Information on infantile colic on the World Wide Web.
AB  - INTRODUCTION: The purpose of this study was to explore and describe the type and
      quality of information on infantile colic that a parent might access on the World
      Wide Web. METHODS: Two checklists were used to evaluate the quality indicators of
      24 Web sites and the colic-specific content. RESULTS: Fifteen health information
      Web sites met more of the quality parameters than the nine commercial sites.
      Eight Web sites included information about colic and infant abuse, with six being
      health information sites. DISCUSSION: The colic-specific content on 24 Web sites
      reflected current issues and controversies; however, the completeness of the
      information in light of current evidence varied among the Web sites. Strategies
      to avoid complications of parental stress or infant abuse were not commonly found
      on the Web sites. Pediatric professionals must guide parents to reliable colic
      resources that also include emotional support and understanding of infant crying.
      A best evidence guideline for the United States would eliminate confusion and
      uncertainty about which colic therapies are safe and effective for parents and
      professionals.

PMID- 22664096
TI  - Conformational selection in trypsin-like proteases.
AB  - For over four decades, two competing mechanisms of ligand recognition-
      conformational selection and induced-fit--have dominated our interpretation of
      protein allostery. Defining the mechanism broadens our understanding of the
      system and impacts our ability to design effective drugs and new therapeutics.
      Recent kinetics studies demonstrate that trypsin-like proteases exist in
      equilibrium between two forms: one fully accessible to substrate (E) and the
      other with the active site occluded (E*). Analysis of the structural database
      confirms existence of the E* and E forms and vouches for the allosteric nature of
      the trypsin fold. Allostery in terms of conformational selection establishes an
      important paradigm in the protease field and enables protein engineers to expand
      the repertoire of proteases as therapeutics.

PMID- 22664099
TI  - The Jewish advantage and household security: life expectancy among 19th Century
      Sephardim of Gibraltar.
AB  - Using the historical population of Gibraltar to examine the pattern of mortality
      of Jews and Roman Catholics revealed that: (1) the Jews exhibited a significantly
      better health status as measured by life expectancy at birth (47.66 and 47.56 for
      Jewish males and females vs. 38.10 and 40.89 for Catholics males and females,
      respectively), (2) most of the disparity is found in the very young age
      categories and (3) the significantly lower rates of deaths could be attributed to
      the diarrheal and nutritional complex. Stage two of the research involved the
      linkage of deaths over a 7-year period relative to their household context as of
      1878. Being Jewish, having a servant, having access to a water well in the
      tenement and residing in a tenement only with other Jews, were all factors that
      contributed to a higher life expectancy. Our explanation for the enhanced
      survivorship among the Jews is grounded in economics as well as in an established
      welfare system, in religious precepts and in secular knowledge of health. One of
      the more notable and hitherto unobserved findings is that Roman Catholics
      residing in the same tenements with Jews enjoyed a distinct health advantage.
      This suggests that a positive amplification effect arose from their co-residence
      with the Jews.

PMID- 22664098
TI  - Assessing basophil functional measures during monoclonal anti-IgE therapy.
AB  - Assessing the impact of therapeutic interventions on the clinical and immunologic
      responses of allergic subjects is a topic of extensive investigation. Available
      approaches include the measurement of in vivo allergen challenge responses,
      serologic measures, or in vitro studies of cells that participate in the allergic
      reaction. Several decades of work support that measures of allergen responses of
      IgE-bearing peripheral blood basophils can reflect clinical expression of
      allergic disease. In the last decade, an immune-based therapy targeting IgE,
      omalizumab, has emerged as an adjunct treatment for a variety of allergic
      diseases. This monoclonal humanized IgG antibody specifically binds circulating
      IgE at a region in the Fc tail that prevents IgE attachment to high affinity IgE
      receptor (FcepsilonRI) bearing cell types such as tissue mast cells and blood
      basophils. This review focuses on methods to monitor changes of basophil allergen
      reactivity with a focus on omalizumab therapy and the implications for clinical
      disease management.

PMID- 22664100
TI  - A screening programme on chronic solvent-induced encephalopathy among Dutch
      painters.
AB  - BACKGROUND: Long-term exposure to organic solvents may lead to chronic solvent
      induced encephalopathy (CSE) in painters. In combination with reduction of
      exposure, a workers' health surveillance programme was developed, resulting in a
      three-stage CSE screening procedure for early neurobehavioural changes possibly
      predicting chronic health effects. The screening consists of a questionnaire
      (Neurosymptom Screening Checklist 60, NSC-60), computerised neurobehavioural
      functioning testing (Neurobehavioural Evaluation System; NES2) and
      multidisciplinary differential diagnostic evaluation by experts (called 'Solvent
      Team'). Results from the screening were compared with the results of the 'care as
      usual' (CAU), in which symptomatic patients were referred directly to the Solvent
      Team by occupational physicians, general practitioners or medical specialists.
      Parallel to the screening programme, a legal ban on indoor use of solvent-based
      paints resulted in lower exposure to solvents. OBJECTIVE: To investigate the
      usefulness of the NSC-60 questionnaire as a screening tool for CSE among painters
      and to investigate the course of the number of CSE cases over the years as a
      potential consequence of improved prevention and control. RESULTS: From 1998 to
      2004, more than 40,000 painters were invited to participate in a health
      surveillance programme including a periodical occupational health examination
      (PHE) and 50% did participate. Four percent (N=794) of these had a positive score
      on the NSC-60. The Solvent Team assessed 101 of these for CSE, which resulted in
      27 CSE cases diagnosed. CAU during the same period of the surveillance (1998
      2004) yielded 619 painters and 75 of these had the diagnosis CSE. After 2002 the
      number of CSE diagnosed cases dropped considerably and in 2004 only one case of
      CSE could be diagnosed. The substantially lower prevalence of CSE diagnosed cases
      in painters after 2002 might partly be explained as a result of a successful
      participation in the screening procedure of most prevalent CSE cases during the
      years 1998-2002. A second reason for the reduction of new diagnosed cases of CSE
      can be the effectiveness of the ban on indoor use of solvent-based paints
      resulting in lower exposure levels at work. CONCLUSION: The screening procedure
      is useful to screen for CSE among people taking part in the PHE programme.
      Control of CSE can be achieved by an integrated preventive approach with
      reduction of exposure and screening on early health effects.

PMID- 22664101
TI  - Neurotoxic exposures and effects: gender and sex matter! Hanninen Lecture 2011.
AB  - Although males and females differ both biologically and in their social and power
      relations throughout their life span, research in environmental and occupational
      neurotoxicology often ignore sex and/or gender as a characteristic that requires
      in-depth consideration. The neurotoxicology literature continues to confuse the
      terms sex (biological attributes) and gender (socially constructed roles and
      behavior) and the words are still used interchangeably. Throughout the lifespan,
      sex and gender are in interaction and both may play a role in influencing
      exposure and effect. Studies that have examined both males and females, provide
      evidence for sex differences in toxicokinetics and responses to neurotoxic
      assault as well as gender differences in exposure patterns, biomarkers of
      exposure, neurobehavioral performance and social consequences. Integrating sex
      and gender considerations into research in neurotoxicology would not only provide
      us with a better understanding of the mechanisms and pathways that lead to toxic
      assault, but also provide a means to improve preventive intervention strategies.

PMID- 22664103
TI  - Engineering of a novel Ca2+-regulated kinesin molecular motor using a calmodulin
      dimer linker.
AB  - The kinesin-microtubule system holds great promise as a molecular shuttle device
      within biochips. However, one current barrier is that such shuttles do not have
      "on-off" control of their movement. Here we report the development of a novel
      molecular motor powered by an accelerator and brake system, using a kinesin
      monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a
      CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355
      M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and
      crosslinkers that react with cysteine residues. Following induction of K355-M13
      dimerization with CaM dimers, we measured K355-M13 motility and found that it can
      be reversibly regulated in a Ca(2+)-dependent manner. We also found that
      velocities of K355-M13 varied depending on the type and crosslink position of the
      CaM dimer used; crosslink length also had a moderate effect on motility. These
      results suggest Ca(2+)-dependent dimerization of K355-M13 could be used as a
      novel molecular shuttle, equipped with an accelerator and brake system, for
      biochip applications.

PMID- 22664102
TI  - Interaction between a plasma membrane-localized ankyrin-repeat protein ITN1 and a
      nuclear protein RTV1.
AB  - The increased tolerance to NaCl 1 (ITN1) protein is a plasma membrane (PM)
      localized protein involved in responses to NaCl stress in Arabidopsis. The
      predicted structure of ITN1 is composed of multiple transmembrane regions and an
      ankyrin-repeat domain that is known to mediate protein-protein interactions. To
      elucidate the molecular functions of ITN1, we searched for interacting partners
      using a yeast two-hybrid assay, and a nuclear-localized DNA-binding protein,
      RTV1, was identified as a candidate. Bimolecular fluorescence complementation
      analysis revealed that RTV1 interacted with ITN1 at the PM and nuclei in vivo.
      RTV1 tagged with red fluorescent protein localized to nuclei and ITN1 tagged with
      green fluorescent protein localized to PM; however, both proteins localized to
      both nuclei and the PM when co-expressed. These findings suggest that RTV1 and
      ITN1 regulate the subcellular localization of each other.

PMID- 22664104
TI  - Interaction of dengue virus nonstructural protein 5 with Daxx modulates RANTES
      production.
AB  - Dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome
      (DSS), caused by dengue virus (DENV) infection, are important public health
      problems in the tropical and subtropical regions. Abnormal hemostasis and plasma
      leakage are the main patho-physiological changes in DHF/DSS. A remarkably
      increased production of cytokines, the so called 'cytokine storm', is observed in
      the patients with DHF/DSS. A complex interaction between DENV proteins and the
      host immune response contributes to cytokine production. However, the molecular
      mechanism(s) by which DENV nonstructural protein 5 (NS5) mediates these responses
      has not been fully elucidated. In the present study, yeast two-hybrid assay was
      performed to identify host proteins interacting with DENV NS5 and a death-domain
      associate protein (Daxx) was identified. The in vivo relevance of this
      interaction was suggested by co-immunoprecipitation and nuclear co-localization
      of these two proteins in HEK293 cells expressing DENV NS5. HEK293 cells
      expressing DENV NS5-K/A, which were mutated at the nuclear localization sequences
      (NLS), were created to assess its functional roles in nuclear translocation, Daxx
      interaction, and cytokine production. In the absence of NLS, DENV NS5 could
      neither translocate into the nucleus nor interact with Daxx to increase the DHF
      associated cytokine, RANTES (CCL5) production. This work demonstrates the
      interaction between DENV NS5 and Daxx and the role of the interaction on the
      modulation of RANTES production.

PMID- 22664105
TI  - Increased stemness and migration of human mesenchymal stem cells in hypoxia is
      associated with altered integrin expression.
AB  - Human mesenchymal stem cells (hMSCs) are regularly cultured and characterised
      under normoxic (21% O(2)) conditions, although the physiological oxygen tension
      in the stem cell niche is known to be as low as 1-2%. Oxygen itself is an
      important signalling molecule, but the distinct impact on various stem cell
      characteristics is still unclear. Therefore, the aim of this study was to
      evaluate the influence of oxygen concentration on the hMSC subpopulation
      composition, cell morphology and migration on different surfaces (polystyrene,
      collagen I, fibronectin, laminin) as well as on the expression of integrin
      receptors. Bone marrow-derived hMSCs were cultured either in normoxic (21% O(2))
      or hypoxic (2% O(2)) conditions. The hMSC subpopulations were assessed by aspect
      ratio and cell area. Hypoxia promoted a more homogeneous cell population with a
      significantly higher fraction of rapidly self-renewing cells which are believed
      to be the true stem cells. Under hypoxic conditions hMSC volume and height were
      significantly decreased on all surfaces as measured by white light confocal
      microscopy. Furthermore, low oxygen tension led to a significant increase in cell
      velocity and Euclidian distance on all matrixes, which was evaluated by time
      lapse microscopy. With regard to cell-matrix contacts, expression of several
      integrin subunits was evaluated by semi-quantitative RT-PCR. Increased expression
      of the subunits alpha(1), alpha(3), alpha(5,) alpha(6), alpha(11), alpha(v),
      beta(1) and beta(3) was observed in hypoxic conditions, while alpha(2) was higher
      expressed in normoxic cultured hMSCs. Taken together, our results indicate that
      hypoxic conditions promote stemness and migration of hMSC along with altering
      their integrin expression.

PMID- 22664106
TI  - Up-regulation of miR-26a promotes apoptosis of hypoxic rat neonatal
      cardiomyocytes by repressing GSK-3beta protein expression.
AB  - Myocardial ischemia is the major cause of morbidity and mortality due to
      cardiovascular diseases. This disease is a severe stress condition that causes
      extensive biochemical changes which trigger cardiac cell death. Stress conditions
      such as deprivation of glucose and oxygen activate the endoplasmic reticulum in
      the cytoplasm of cells, including cardiomyocytes, to generate and propagate
      apoptotic signals in response to these conditions. microRNAs (miRNAs) are a class
      of small non-coding RNAs that mediate posttranscriptional gene silencing. The
      miRNAs play important roles in regulating cardiac physiological and pathological
      events such as hypertrophy, apoptosis, and heart failure. However, the roles of
      miRNAs in reactive oxygen species (ROS)-mediated injury on cardiomyocytes are
      uncertain. In this study, we identified at the apoptotic concentration of
      H(2)O(2), miR-26a expression was increased. To determine the potential roles of
      miR-26a in H(2)O(2)-mediated cardiac apoptosis, miR-26a expression was regulated
      by a miR-26a or an anti-miR-26a. Overexpression of miR-26a increased apoptosis as
      determined by upregulation of Annexin V/PI positive cell population, caspase-3
      activity and expression of pro-apoptotic signal molecules, whereas inhibition of
      miR-26a reduced apoptosis. We identified GSK3B as a direct downstream target of
      miR-26a. Furthermore, miR-26a attenuated viability and increased caspase-3
      activity in normal cardiomyocytes. This study demonstrates that miR-26a promotes
      ROS-induced apoptosis in cardiomyocytes. Thus, miR-26a affects ROS-mediated gene
      regulation and cellular injury response.

PMID- 22664108
TI  - TIMP2 deficient mice develop accelerated osteoarthritis via promotion of
      angiogenesis upon destabilization of the medial meniscus.
AB  - Vascular invasion into the normally avascular articular surface is a hallmark of
      advanced osteoarthritis (OA). In this study, we demonstrated that the expression
      of tissue inhibitor of metalloproteinases-2 (TIMP2), an anti-angiogenic factor,
      was present at high levels in normal articular chondrocytes, and was drastically
      decreased shortly after destabilization of the medial meniscus (DMM). We also
      investigated the anti-angiogenic properties of TIMP2 via knockout. We
      hypothesized that the loss of TIMP2 could accelerate osteoarthritis development
      via promotion of angiogenesis. Loss of TIMP2 led to increased periarticular
      vascular formation 1 month post DMM, compared to wild-type mice, and did so
      without altering the expression pattern of matrix metalloproteinases and vascular
      endothelial growth factors. The increased vascularization eventually resulted in
      a severe degeneration of the articular surface by 4 months post DMM. Our findings
      suggest that reduction of TIMP2 levels and increased angiogenesis are possible
      primary events in OA progression. Inhibiting or delaying angiogenesis by TIMP2
      expression or other anti-angiogenic therapies could improve OA prevention and
      treatment.

PMID- 22664109
TI  - Dynamic secondary structural changes in Ca2+-saturated calmodulin upon
      interaction with the antagonist, W-7.
AB  - Although the 3D structure of the Ca(2+)-bound CaM (Ca(2+)/CaM) complex with the
      antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), has been
      resolved, the dynamic changes in Ca(2+)/CaM structure upon interaction with W-7
      are still unknown. We investigated time- and temperature-dependent dynamic
      changes in Ca(2+)/CaM interaction with W-7 in physiological conditions using one-
      and two-dimensional Fourier-transformed infrared spectroscopy (2D-IR). We
      observed changes in the alpha-helix secondary structure of Ca(2+)/CaM when
      complexed with W-7 at a molar ratio of 1:2, but not at higher molar ratios
      (between 1:2 and 1:5). Kinetic studies revealed that, during the initial 125s at
      25 degrees C, Ca(2+)/CaM underwent formation of secondary coil and turn
      structures upon binding to W-7. Variations in temperature that induced
      significant changes in the structure of the Ca(2+)/CaM complex failed to do so
      when Ca(2+)/CaM was complexed with W-7. We concluded that W-7 induced stepwise
      conformational changes in Ca(2+)/CaM that resulted in a rigidification of the
      complex and its inability to interact with target proteins and/or polypeptides.

PMID- 22664107
TI  - Dissecting the role of disulfide bonds on the amyloid formation of insulin.
AB  - Disulfide bonds play a critical role in the stability and folding of proteins.
      Here, we used insulin as a model system, to investigate the role of its
      individual disulfide bond during the amyloid formation of insulin. Tris(2
      carboxyethyl)phosphine (TCEP) was applied to reduce two of the three disulfide
      bonds in porcine insulin and the reduced disulfide bonds were then alkylated by
      iodoacetamide. Three disulfide bond-modified insulin analogs, INS-2 (lack of A6
      A11), INS-3 (lack of A7-B7) and INS-6 (lack of both A6-A11 and A7-B7), were
      obtained. Far-UV circular dichroism (CD) spectroscopy results indicated that the
      secondary structure of INS-2 was the closest to insulin under neutral conditions,
      followed by INS-3 and INS-6, whereas in an acidic solution all analogs were
      essentially unfolded. To test how these modifications affect the amyloidogenicity
      of insulin, thioflavin-T (ThT) fluorescence and transmission electronic
      microscopy (TEM) were performed. Our results showed that all analogs were more
      prone to aggregation than insulin, with the order of aggregation rates being INS
      6>INS-3>INS-2. Cross-linking of unmodified proteins (PICUP) assay results showed
      that analogs without A6-A11 (INS-2 and INS-6) have a higher potential for
      oligomerization than insulin and INS-3, which is accompanied with a higher
      cytotoxicity as the hemolytic assays of human erythrocytes suggested. The results
      indicated that breakage of A7-B7 induced more unfolding of the insulin structure
      and a higher amyloidogenicity than breakage of A6-A11, but breakage of A6-A11
      caused a significant cytotoxicity increase and a higher potency to form high
      order toxic oligomers.

PMID- 22664110
TI  - Prognostic significance of HOXB4 in de novo acute myeloid leukemia.
AB  - As research into hematopoiesis advances, new factors associated with
      hematopoietic stem cell (HSC) activity have been discovered, and the contribution
      of HSC factors to hematopoiesis is now actively being investigated. Since the
      involvement of stem cells is considered to be important in hematological
      malignancies as well as normal hematopoiesis, we examined the expression of newly
      defined HSC factors including HOXB4, TCFEC, HMGB-1, FOS, and SPI-1 in the bone
      marrow (BM) from de novo acute myeloid leukemia (AML) patients. Expression levels
      of mRNA extracted from frozen specimens of AML patients and normal controls were
      measured by real-time polymerase chain reaction (PCR). Among the HSC factors,
      HOXB4 exhibited significantly higher expression in the BM of AML as compared with
      normal controls. Immunostaining for HOXB4 revealed that the HOXB4-positive cell
      ratios correlated well with the expression levels of mRNA for HOXB4 in AML BM.
      Based on the HOXB4-positive cell ratio, AML patients were divided into two groups
      (cases with higher ratios and lower ratios). The group with higher HOXB4-positive
      cell ratios had better prognoses as compared with the group with lower ratios.
      Multivariate analysis confirmed the HOXB4-positivity as an independent predictor
      of overall survival of AML patients. Lastly, mRNA expression levels for HOXB4
      were inversely correlated with the expression levels of at least two genes,
      including ABCB1, which is known to be a multidrug-resistance gene. Our study
      distinguishes a subgroup of AML with higher HOXB4 expression and better
      prognosis, and this might be reflected by relative drug sensitivity in leukemic
      cells.

PMID- 22664111
TI  - A particular expression pattern of CD13 epitope 7H5 in chronic lymphocytic
      leukaemia--a possible new therapeutic target.
AB  - A total of 50 patients with chronic lymphocytic leukaemia (CLL), as well as the B
      cell leukaemia cell lines MEC-1, JVM-3, and BV-173 were studied in order to
      assess the incidence of CD13/aminopeptidase N (APN) immunolabelling with a
      monoclonal antibody 7H5 compared to LeuM7 and to CD13 mRNA levels, and to
      correlate these data with the cytotoxic and apoptosis-induction activity of the
      natural phenolic APN inhibitor curcumin. CD13/APN was detected in a significant
      proportion of B-CLL patients (42/50, 84%), immunolabelled by 7H5 (42/50) +/-
      LeuM7 (10/50). Molecular analysis for CD13 transcripts confirmed these data,
      resulting in a specific RT-PCR product in CD13 positive cases. Curcumin showed
      concentration-dependent cytoreductive efficacy and apoptosis-induction activity
      in all tested cell lines and primary cultures from CLL mononuclear cells. There
      was a clear tendency for a better response in CD13 positive cases. The incidence
      of CD13/APN in CLL suggests that the inhibition of APN/CD13 by curcumin may be an
      effective new molecular target for a more efficient therapy for these patients
      and warrants further investigations.

PMID- 22664112
TI  - Treatment of hairy cell leukemia: long-term results in a developing country.
AB  - Twenty-nine consecutive patients with hairy cell leukemia (HCL) were treated in
      two institutions with interferon (IFN, n = 18) or cladribine (n = 11), between
      July 1987 and May 2011. Median age was 62 (range 29-83) years; there were 21
      males and 8 females. Seven of the 18 patients in the IFN group (39%) achieved a
      complete remission (CR), whereas all the patients in the 2-CDA group entered a
      CR. Three patients in the 2-CDA group relapsed and needed an additional course of
      the drug, 2, 3 and 6 years after the initial one. The median overall survival
      (OS) of the whole group has not been reached, being above 217 months, the 217
      month OS being 91%. The survival of patients treated with either IFN or 2-CDA was
      not statistically different (94% OS at 217 months versus 91% OS at 133 months,
      respectively). The data that we present here suggest that treatment of HCL with
      either 2-CDA or IFN is equally effective; treatment costs with IFN are
      substantially lower than those of the purine analog.

PMID- 22664113
TI  - Interleukin-8 in the pathogenesis of primary central nervous system lymphoma in
      association with HIV infection.
AB  - The pathogenesis of acquired immunodeficiency syndrome-associated primary central
      nervous system lymphoma (AIDS-associated PCNSL) remains unclear. However, cell
      adhesion molecules have been reported to be strongly associated with PCNSL. In
      this study, we established Epstein-Barr virus (EBV)-transformed lymphoblastoid
      cell lines (LCLs) from HIV-positive patients (LCL(HIV)) and normal individuals
      (LCL(N)). The expression of CD18 antigen by LCL(HIV) was stronger than that by
      LCL(N). We performed a cell adhesion assay using ISO-HAS, which is the human
      hemangiosarcoma cell line and expresses intercellular adhesion molecule 1 (CD54).
      The binding rates of LCL(HIV) and ISO-HAS without stimulation were higher than
      those of LCL(N). Further, we demonstrated that azidothymidine or simvastatin
      inhibited the binding rates of LCL(HIV) and ISO-HAS more significantly than those
      of LCL(N). Further, the levels of interleukin (IL)-8, a CD18 inducer, were higher
      in LCL(HIV) than in LCL(N). We conclude that interaction between IL-8 and CD18
      may be critical to AIDS-related PCNSL.

PMID- 22664114
TI  - Biomarkers and early detection of late onset anthracycline-induced cardiotoxicity
      in children.
AB  - BACKGROUND: The main strategy for minimizing anthracycline cardiotoxicity is
      early detection of high-risk patients. AIM OF THE STUDY: To investigate the role
      of cardiac biomarkers; cardiac troponin T (cTnT) and N-terminal probrain
      natriuretic peptide (NT-pro-BNP), and tissue Doppler imaging (TDI), as early
      predictors of chronic cardiotoxicity in survivors of acute leukemia. PATIENTS AND
      METHODS: We carried a retrospective study on 50 asymptomatic survivors of acute
      leukemia who received anthracycline in their treatment protocols. All patients
      underwent blood sampling to determine the levels of NT-pro-BNP and cTnT along
      with conventional echocardiography and TDI. RESULTS: None had abnormal cTnT
      levels. About 20% had abnormal NT-pro-BNP levels. Diastolic dysfunction of the
      left ventricle was the most significant in conventional echocardiography. TDI was
      superior as it detected myocardial affection in 10% more than echo. TDI
      demonstrated global myocardial damage with significant aberrations in peak
      myocardial velocities and ratios. CONCLUSIONS: NT-pro-BNP can be used as a
      sensitive cardiac biomarker in monitoring of anthracycline-induced
      cardiotoxicity. Follow up is essential to validate the role of NT-pro-BNP as an
      early marker for late onset anthracycline-induced cardiotoxicity. Tissue Doppler
      is marvelous as it could detect early cardiac dysfunction even in those with
      normal study by conventional echocardiography.

PMID- 22664115
TI  - Targeted inhibition of VEGF-modulated survival and arsenic sensitivity in acute
      myeloid leukemia (AML).
AB  - Vascular endothelial growth factor (VEGF) is a specific growth factor for tumor
      associated angiogenesis, and is also involved in leukemogenesis; however, its
      exact role in leukemia development remains elusive. In this study we used
      antisense oligonucleotide (AS) to manipulate VEGF function in acute myeloid
      leukemia (AML). HL60 and primary AML cells were transfected with VEGF AS (0.3
      umol/l). Cell proliferation and survival were assessed using the trypan blue
      exclusion assay. The viability of cells was determined using MTT. The IC50 values
      of arsenic trioxide (ATO) in HL60 cell were calculated by ICp software. The
      results showed that VEGF AS effectively inhibited AML cell proliferation and
      survival 72 hours post-transfection and exhibited time dependence. The IC50 value
      of ATO was significantly down-regulated by VEGF AS in HL60. Meanwhile, VEGF AS
      alone induced cell apoptosis, and promoted ATO-induced apoptosis. There is
      synergistic inhibitory effects between AS and ATO. VEGF AS down-regulated VEGF
      protein level in the supernatants and cellular VEGF mRNA level by western blot
      and real-time PCR. Therefore, targeted inhibition of VEGF suppressed survival and
      increased arsenic sensitivity in AML.

PMID- 22664116
TI  - Valproic acid inhibits proliferation of EB virus-infected natural killer cells.
AB  - There is no recognized treatment for Epstein-Barr virus (EBV)-associated natural
      killer (NK) cell lymphoproliferative disorders (LPDs). To determine the
      possibility of histone deacetylase inhibitors as a therapeutic tool for such
      disorders, we investigated the anti-proliferative effects of valproic acid (VPA)
      on two EBV-infected NK cell lines (KAI3 and NKED). VPA inhibited the growth of
      both lines in a dose- and time-dependent manner by inducing histone
      hyperacetylation. G1 cell cycle arrest was induced at 24 hours and was associated
      with increased expression of p21(WAF1), p27(Kip1), and cyclin E and decreased
      expression of cyclin D2, CDK4, and c-myc. Sub-G1 fractions were not significantly
      changed at 24 hours, whereas cleaved caspase-3 and cleaved PARP were already
      detected, and the extrinsic apoptotic pathway, determined by cleaved caspase-8,
      was activated. Finally, sub-G1 accumulation was increased after 72 hours
      following stimulation. These findings indicate that VPA might be a therapeutic
      option for EBV-associated NK-cell LPDs.

PMID- 22664117
TI  - MicroRNAs in hematological malignancies: a novel approach to targeted therapy.
AB  - MicroRNAs (miRNAs) are about 19-24 nucleotide small single-stranded noncoding
      RNAs that are involved in crucial cell processes such as proliferation,
      apoptosis, and differentiation. Several studies reported show the involvement of
      miRNA in cancer. It has been suggested that miRNA  profiling has the potential to
      classify a variety of tumors and possibly predict outcome. MicroRNA can act as an
      oncogene as well as tumor suppressor gene and this dual function of miRNA can be
      utilized as a therapeutic tool. The oncogenic character of miRNA can be silenced
      through various  RNA interference-type strategies. The involvement of miRNA in
      the tumorogenesis processes makes them an important therapeutic tool and a novel
      biomarker. In this review, we have highlighted the role of miRNA in hematological
      malignancies and its utility in targeted therapy.

PMID- 22664118
TI  - Frequency of thrombophilic genetic polymorphisms among Saudi subjects compared
      with other populations.
AB  - Thrombophilic mutations increase the tendency toward thromboembolic disease. The
      aim of this study was to estimate the prevalence of the genetic variants related
      to thrombophilia among Saudis compared with other populations. Real-time
      polymerase chain reaction (PCR) genotyping was carried  out to determine the
      polymorphic variants of factor V Leiden 1695G/A, prothrombin 20210G/A, plasmin
      activator inhibitor 1 4G/5G, methylene tetrahydrofolate reductase (MTHFR) 677C/T,
      MTHFR 1298A/C, and angiotensin-converting enzyme (ACE) insertion/deletion (I/D)
      among a representative sample  of healthy Saudi subjects. Carraige rate for each
      of the mutant variants of factor V Leiden (FVL) and FII genes constituted 2% of
      the surveyed subjects giving an allele frequency of 0.01, homozygous forms of
      plasminogen activator inhibitor-1 (PAI-1) gene 4G/4G, MTHFR 677TT, 1298CC, and
      ACE  DD were present among 7.7, 2.55, 7, and 51.8% of subjects with a mutant
      allele frequency of 0.4, 0.19, 0.29, and 0.73, respectively. This study showed
      that the Saudi population has a peculiar pattern regarding thrombophilic
      mutations that might warrant additional considerations for prophylaxis.

PMID- 22664119
TI  - The effect of combined therapy with deferoxamine and deferiprone on serum
      ferritin level of beta-thalassemic patients.
AB  - OBJECTIVE: To determine the effect of combined therapy with deferoxamine and
      deferiprone on serum ferritin level of beta-thalassemic patients. METHOD AND
      MATERIALS: This controlled clinical trial was conducted on 26 major beta
      thalassemic patients. Twelve patients in case group received deferiprone 75
      mg/kg/day three times a day (TDS) orally with deferoxamine 30-50 mg/kg
      subcutaneously every other day. Fourteen patients in control group received
      deferoxamine 30-50 mg/kg/day subcutaneously for 6-12 hours/day and 5-6 days per
      week. Serum ferritin level was measured at the beginning and at the end of the
      third and the sixth months of study. Side effects of combined therapy were
      assessed. Data were analyzed by SPSS software v: 16.0 and t-Student and compared
      t-tests. RESULTS: The mean of serum ferritin level in case group significantly
      decreased from 7539.8 +/- 3434.9 ug/l at the beginning of study to 4848.7 +/-
      2706.2 ug/l (P < 0.001) and to 4338.3 +/- 2308.8 ug/l (P < 0.001) at the end of
      the third and the sixth months of study, respectively. The mean of serum ferritin
      level in control group insignificantly increased from 5668 +/- 3613.8 to 6210.8
      +/- 3940.9 ug/l and to 5742 +/- 3205.9 ug/l at the end of the third and the sixth
      months of study, respectively. The common side effects of combined therapy were
      nausea (8.3%) and arthropathy (8.3%). A mild transient neutropenia and liver
      enzymes elevation happened in four patients of case group. CONCLUSION: Combined
      therapy with deferoxamine and deferiprone significantly decreases serum ferritin
      level. It has little side effect and is suggested for major beta-thalassemic
      patients as a suitable therapy.

PMID- 22664120
TI  - The physiology and molecular biology of sponge tissues.
AB  - Sponges have become the focus of studies on molecular evolution and the evolution
      of animal body plans due to their ancient branching point in the metazoan
      lineage. Whereas our former understanding of sponge function was largely based on
      a morphological perspective, the recent availability of the first full genome of
      a sponge (Amphimedon queenslandica), and of the transcriptomes of other sponges,
      provides a new way of understanding sponges by their molecular components. This
      wealth of genetic information not only confirms some long-held ideas about sponge
      form and function but also poses new puzzles. For example, the Amphimedon sponge
      genome tells us that sponges possess a repertoire of genes involved in control of
      cell proliferation and in regulation of development. In vitro expression studies
      with genes involved in stem cell maintenance confirm that archaeocytes are the
      main stem cell population and are able to differentiate into many cell types in
      the sponge including pinacocytes and choanocytes. Therefore, the diverse roles of
      archaeocytes imply differential gene expression within a single cell
      ontogenetically, and gene expression is likely also different in different
      species; but what triggers cells to enter one pathway and not another and how
      each archaeocyte cell type can be identified based on this gene knowledge are new
      challenges. Whereas molecular data provide a powerful new tool for interpreting
      sponge form and function, because sponges are suspension feeders, their body plan
      and physiology are very much dependent on their physical environment, and in
      particular on flow. Therefore, in order to integrate new knowledge of molecular
      data into a better understanding the sponge body plan, it is important to use an
      organismal approach. In this chapter, we give an account of sponge body
      organization as it relates to the physiology of the sponge in light of new
      molecular data. We focus, in particular, on the structure of sponge tissues and
      review descriptive as well as experimental work on choanocyte morphology and
      function. Special attention is given to pinacocyte epithelia, cell junctions, and
      the molecules present in sponge epithelia. Studies describing the role of the
      pinacoderm in sensing, coordination, and secretion are reviewed. A wealth of
      recent work describes gene presence and expression patterns in sponge tissues
      during development, and we review this in the context of the previous
      descriptions of sponge morphology and physiology. A final section addresses
      recent findings of genes involved in the immune response. This review is far from
      exhaustive but intends rather to revisit for non-specialists key aspects of
      sponge morphology and physiology in light of new molecular data as a means to
      better understand and interpret sponge form and function today.

PMID- 22664121
TI  - Sponge-microbe symbioses: recent advances and new directions.
AB  - Sponges can host abundant and diverse communities of symbiotic microorganisms. In
      this chapter, we review recent work in the area of sponge-microbe symbioses,
      focusing on (1) the diversity of these associations, (2) host specificity, (3)
      modes of symbiont transmission, and (4) the positive and negative impacts of
      symbionts on their hosts. Over the past 4 years, numerous studies have catalogued
      the diversity of sponge-microbe symbioses, challenging previous hypotheses of a
      uniform, vertically transmitted microbial community and supporting a mixed model
      of symbiont community transmission. We emphasize the need for experimental
      manipulations of sponge-symbiont interactions coupled with advanced laboratory
      techniques to determine the identity of metabolically active microbial symbionts,
      to investigate the physiological processes underlying these interactions, and to
      elucidate whether symbionts act as mutualists, commensals, or parasites. The
      amazing diversity of these complex associations continues to offer critical
      insights into the evolution of symbiosis and the impacts of symbiotic microbes on
      nutrient cycling and other ecosystem functions.

PMID- 22664122
TI  - Nutrient fluxes through sponges: biology, budgets, and ecological implications.
AB  - Marine sponges are able to process a variety of carbon (C), nitrogen (N),
      phosphorous (P), and silicon (Si) dissolved compounds, in addition to the
      particulate C, N, and P obtained through regular feeding. While Si fluxes through
      sponges are exclusively related to the elaboration of their skeleton of biogenic
      silica, C, N, and P fluxes derive from a complex combination of metabolic
      processes that include feeding, respiration, egestion, excretion, as well as
      hosting of large microbial populations within the sponge body. Because of the
      remarkable abundance of sponges in many benthic marine communities, they have the
      potential to impact the availability of the compounds they take up and release,
      affecting the benthic-pelagic coupling and cycling rates of chemical elements
      that are crucial to determine growth of bacterioplankton and primary producers at
      the ecosystem level. Unfortunately, our knowledge and understanding of the
      magnitude of the sponge-meditated nutrient fluxes and their ecological
      implications depends much on the compound type (i.e. C, N, P, or Si). Herein, we
      review the available knowledge on the subject with emphasis on recent
      developments.

PMID- 22664123
TI  - Sponge chemical diversity: from biosynthetic pathways to ecological roles.
AB  - Since more than 50 years, sponges have raised the interest of natural product
      chemists due to the presence of structurally original secondary metabolites.
      While the main objective were first to discover new drugs from the Sea, a large
      number of interrogations arose along with the isolation and structure
      elucidations of a wide array of original architectures and new families of
      natural products not found in the terrestrial environment. In this chapter, we
      focus on the results obtained during this period on the following questions. A
      preliminary but still unresolved issue to be addressed will be linked to the role
      of the microbiota into the biosynthesis of these low-weight compounds. Our
      knowledge on the biosynthetic pathways leading to plant secondary metabolites is
      now well established, and this background will influence our comprehension of the
      biosynthetic events occurring in a sponge. But is the level of similarity between
      both metabolisms so important? We clearly need more experimental data to better
      assess this issue. This question is of fundamental interest because sponges have
      a long evolutionary history, and this will allow a better understanding on the
      transfer of the genetic information corresponding to the biosynthesis of
      secondary metabolites. After the how, the why! The question of the ecological
      role of these metabolites is also of high importance first not only because they
      can serve as synapomorphic characters but also because they may represent
      chemical cues in the water environment. Even if most of these compounds are
      considered as defensive weapons for these sessile invertebrates, they may also be
      linked to physiological characters as the reproduction. Finally, a metabolomic
      approach can appear as a complementary tool to give additional information on the
      sponge fitness. All the new developments in molecular biology and bioanalytical
      tools will open the way for a better comprehension on the complex field of sponge
      secondary metabolites.

PMID- 22664124
TI  - Biosilica: Molecular Biology, Biochemistry and Function in Demosponges as well as
      its Applied Aspects for Tissue Engineering.
AB  - Biomineralization, biosilicification in particular (i.e. the formation of
      biogenic silica, SiO(2)), has become an exciting source of inspiration for the
      development of novel bionic approaches following 'nature as model'. Siliceous
      sponges are unique among silica-forming organisms in their ability to catalyze
      silica formation using a specific enzyme termed silicatein. In this study, we
      review the present state of knowledge on silicatein-mediated 'biosilica'
      formation in marine demosponges, the involvement of further molecules in silica
      metabolism and their potential applications in nano-biotechnology and bio
      medicine. While most forms of multicellular life have developed a calcium-based
      skeleton, a few specialized organisms complement their body plan with silica.
      Only sponges (phylum Porifera) are able to polymerize silica enzymatically
      mediated in order to generate massive siliceous skeletal elements (spicules)
      during a unique reaction, at ambient temperature and pressure. During this
      biomineralization process (i.e. biosilicification), hydrated, amorphous silica is
      deposited within highly specialized sponge cells, ultimately resulting in
      structures that range in size from micrometres to metres. This peculiar
      phenomenon has been comprehensively studied in recent years, and in several
      approaches, the molecular background was explored to create tools that might be
      employed for novel bioinspired biotechnological and biomedical applications.
      Thus, it was discovered that spiculogenesis is mediated by the enzyme silicatein
      and starts intracellularly. The resulting silica nanoparticles fuse and
      subsequently form concentric lamellar layers around a central protein filament,
      consisting of silicatein and the scaffold protein silintaphin-1. Once the growing
      spicule is extruded into the extracellular space, it obtains final size and
      shape. Again, this process is mediated by silicatein and silintaphin
      1/silintaphin-1, in combination with other molecules such as galectin and
      collagen. The molecular toolbox generated so far allows the fabrication of novel
      micro- and nano-structured composites, contributing to the economical and
      sustainable synthesis of biomaterials with unique characteristics. In this
      context, first bioinspired approaches implement recombinant silicatein and
      silintaphin-1 for applications in the field of biomedicine (biosilica-mediated
      regeneration of tooth and bone defects) with promising results.

PMID- 22664125
TI  - Cultivation of sponges, sponge cells and symbionts: achievements and future
      prospects.
AB  - Marine sponges are a rich source of bioactive compounds with pharmaceutical
      potential. Since biological production is one option to supply materials for
      early drug development, the main challenge is to establish generic techniques for
      small-scale production of marine organisms. We analysed the state of the art for
      cultivation of whole sponges, sponge cells and sponge symbionts. To date,
      cultivation of whole sponges has been most successful in situ; however, optimal
      conditions are species specific. The establishment of sponge cell lines has been
      limited by the inability to obtain an axenic inoculum as well as the lack of
      knowledge on nutritional requirements in vitro. Approaches to overcome these
      bottlenecks, including transformation of sponge cells and using media based on
      yolk, are elaborated. Although a number of bioactive metabolite-producing
      microorganisms have been isolated from sponges, and it has been suggested that
      the source of most sponge-derived bioactive compounds is microbial symbionts,
      cultivation of sponge-specific microorganisms has had limited success. The
      current genomics revolution provides novel approaches to cultivate these
      microorganisms.

PMID- 22664126
TI  - Preface.

PMID- 22664127
TI  - Antagonists of 5-HT6 receptors. Substituted 3-(phenylsulfonyl)pyrazolo[1,5
      a]pyrido[3,4-e]pyrimidines and 3-(phenylsulfonyl)pyrazolo[1,5-a]pyrido[4,3
      d]pyrimidines-Synthesis and 'structure-activity' relationship.
AB  - Synthesis and biological evaluation of a new series of structurally unrestricted
      and intramolecular hydrogen bond restricted derivatives of 3
      (phenylsulfonyl)pyrazolo[1,5-a]pyrido[3,4-e]pyrimidines (angular tricyclics) and
      3-(phenylsulfonyl)pyrazolo[1,5-a]pyrido[4,3-d]pyrimidines (linear tricyclics) are
      described. Structurally restricted derivatives are highly potent and selective
      blockers of 5-HT(6) receptors with little difference between angular or linear
      shape of the tricyclic core, the angular species being only slightly more potent.
      The angular representative of 3-(phenylsulfonyl)pyrazolo[1,5-a]pyrido[3,4
      e]pyrimidines, 5, can be considered as more favorable candidate for further
      development as it shows only weak 5-HT(2B) blocking activity (IC(50)=6.16 MUM as
      compared with IC(50)=1.8 nM for 5-HT(6) receptors) and very low hERG potassium
      channel blocking potency (IC(50)=54.2 MUM). The linear analog, 11, is less
      favorable as while showing no binding to the 5-HT(2B) receptor at concentrations
      of up to 10 MUM, it exhibits quite a high potency to block the hERG channel
      (IC(50)=0.5 MUM).

PMID- 22664128
TI  - SAR analysis of a series of acylthiourea derivatives possessing broad-spectrum
      antiviral activity.
AB  - A series of acylthiourea derivatives were designed, synthesized, and evaluated
      for broad-spectrum antiviral activity with selected viruses from Poxviridae
      (vaccinia virus) and two different genera of the family Bunyaviridae (Rift Valley
      fever and La Crosse viruses). A compound selected from a library screen, compound
      1, displayed submicromolar antiviral activity against both vaccinia virus
      (EC(50)=0.25 MUM) and La Crosse virus (EC(50)=0.27 MUM) in cytopathic effect
      (CPE) assays. SAR analysis was performed to further improve antiviral potency and
      to optimize drug-like properties of the initial hits. During our analysis, we
      identified 26, which was found to be nearly fourfold more potent than 1 against
      both vaccinia and La Crosse viruses. Selected compounds were further tested to
      more fully characterize the spectrum of antiviral activity. Many of these
      possessed single digit micromolar and sub-micromolar antiviral activity against a
      diverse array of targets, including influenza virus (Orthomyxoviridae), Tacaribe
      virus (Arenaviridae), and dengue virus (Flaviviridae).

PMID- 22664129
TI  - Development of novel linkers to conjugate pharmacophores to a carrier antibody.
AB  - We have developed modified maleimide novel linkers with improved chemical
      stability that could potentially be used in conjugating various pharmacophores
      such as oligo nucleotides, peptides, and proteins to antibodies to afford novel
      biologics with well-defined therapeutic benefits and improved pharmacokinetic
      properties. These linkers expand the array of tools available for bioconjugation
      of pharmacophores to antibodies.

PMID- 22664130
TI  - Tri-substituted acylhydrazines as tertiary amide bioisosteres: HCV NS5B
      polymerase inhibitors.
AB  - The use of a tri-substituted acylhydrazine as an isostere of a tertiary amide was
      explored in a series of HCV NS5B thumb site II inhibitors. Direct replacement
      generated an analog with similar conformational and physicochemical properties.
      The series was extended to produce compounds with potent binding affinities and
      encouraging levels of cellular potency.

PMID- 22664131
TI  - Iridoid glucosides and a C13-norisoprenoid from Lamiophlomis rotata and their
      effects on NF-kappaB activation.
AB  - Four new iridoid glucosides, 7-dehydroxyzaluzioside (1), 6'-O
      syringylphlorigidoside C (2), barlerin-6"-hydroxy-2",6"-dimethylocta-2",7"
      dienate ester (3), 6beta-n-butoxy-7,8-dehydropenstemonoside (4), and a new C(13)
      norisoprenoid derivative, 5beta,6alpha-dihydroxy-3beta-(beta-D-glucoyranosyloxy)
      7-megastigmen-9-one (5), together with 16 known iridoid glucosides, were isolated
      from Lamiophlomis rotata. The structures of these new compounds were elucidated
      by HRMS, 1D and 2D NMR spectroscopy. A stable nuclear factor kappaB (NF-kappaB)
      luciferase-expressing human embryonic kidney 293 cell line was used in the
      luciferase assay for monitoring the anti-inflammatory activity of the compounds.
      It was found that 6beta-n-butoxy-7,8-dehydropenstemonoside (4) and two known
      compounds (8-epi-7-deoxyloganin and 7,8-dehydropenstemonoside) had a significant
      inhibitory effect on lipopolysaccharide-stimulated NF-kappaB activation.

PMID- 22664133
TI  - Differential regulation of mitogen-activated protein kinase signaling pathways in
      human with different types of mitral valvular disease.
AB  - BACKGROUND: Mitogen-activated protein kinases (MAPKs) are considered to play a
      prominent role in cardiac development, function, and pathogenesis. The different
      types of mitral valvular disease (MVD), including mitral regurgitation (MR) and
      mitral stenosis (MS), have different underlying pathophysiologic changes, but the
      precise intracellular signal transduction mechanisms are not clear. Thus, we
      investigated the differential regulation of MAPK signaling pathways in humans
      with different types of MVD. METHODS: Left atrial appendage tissue samples from
      32 patients with MVD who were undergoing mitral valve replacement surgery were
      studied. Serum angiotensin II concentrations were measured using enzyme-linked
      immunosorbent assay. The expression of MAPK pathway-related genes and proteins
      was assessed using quantitative polymerase chain reaction, Western blot, and
      immunohistochemistry. RESULTS: Echocardiography showed that patients with MS had
      a greater left atrial pressure overload than those with MR. The relative amounts
      of angiotensin II, extracellular signal-regulated kinase 1, p38alpha, c-Jun N
      terminal kinase 2, c-Fos, activating transcription factor 2, and c-Jun mRNA were
      significantly upregulated in those with MS compared with those with MR (P <
      0.05). The serum angiotensin II concentrations were significantly increased in
      those with MS compared with those with MR (P = 0.017). Substantial changes in the
      phosphorylated forms of the MAPK proteins were detected. Phosphorylated
      extracellular signal-regulated kinase 1/2, and phosphorylated p38 were
      significantly increased in those with MS compared with those with MR (P < 0.001),
      and phosphorylated c-Jun N-terminal kinase in the MR group was significantly
      greater than that in the MS group (P < 0.001). Histologically, more serious
      myocardial cells losses, myolysis, and interstitial fibrosis were detected in the
      MS group. CONCLUSIONS: The different types of MVD have different hemodynamic
      characteristics, and different MAPK pathways were activated in the MR and MS
      groups, which could lead to diverse left atrial histologic changes.

PMID- 22664134
TI  - Fluoro-D-glucose-micro positron emission tomography as a diagnostic tool to
      confirm brain death in a murine donor lung injury model.
AB  - PURPOSE: Because brain death (BD)-related donor lung injury is still poorly
      understood, a reliable mouse model can help in understanding the immunologic
      mechanisms behind this lung injury. The purpose of our study was to validate BD
      in mice using small-animal positron emission tomography. PROCEDURES: BD was
      induced in male Balb/c mice (27.1 +/- 0.9 g) with an intracranial balloon
      catheter inflated rapidly (<1 min) [BD](R) or gradually (36 +/- 5 min) [BD](G),
      and compared with sham-operated [SH] and control animals [C] (n = 6/group). Ten
      minutes after balloon insertion 10.4 +/- 1.0 MBq 2-deoxy-2-[(18)F]-fluoro-D
      glucose ((18)FDG) was administered intravenously and static images were performed
      and quantified. RESULTS: Coronal, sagittal, and transaxial sections of cerebral
      (18)FDG activity revealed significant differences when comparing [BD](R) and
      [BD](G) with [C] and [SH] animals. No significant (18)FDG uptake was visually
      detectable in [BD](R) and [BD](G). The percentage injected dose showed
      significant differences between BD groups and [C] and [SH] (P < 0.0001). No
      significant difference was seen between [C] versus [SH] nor between [BD](R)versus
      [BD](G) (P > 0.05). CONCLUSIONS: (18)FDG micro positron emission tomography
      imaging is a valuable tool to demonstrate brain functionality and can therefore
      be used as a surrogate test to confirm BD in mice.

PMID- 22664132
TI  - Bone flap perfusion assessment using near-infrared fluorescence imaging.
AB  - BACKGROUND: Microsurgical vascularized bone flaps are a versatile technique for
      reconstructing large bone defects. However, the assessment of perfusion is
      challenging, because clinical examination is difficult intraoperatively and often
      not possible postoperatively. Therefore, it is important to develop techniques to
      assess the perfusion of vascularized bone flaps and potentially improve the
      surgical outcomes. Near-infrared (NIR) fluorescence imaging has previously been
      shown to provide real-time, intraoperative evaluation of vascular perfusion. The
      present pilot study investigated the ability of NIR imaging to assess the
      perfusion of vascularized bone flaps. METHODS: Vascularized bone flaps were
      created in female Yorkshire pigs using well-established models for porcine
      forelimb osteomyocutaneous flap allotransplantation (n = 8) and hindlimb fibula
      flaps (n = 8). Imaging of the bone flaps was performed during harvest using the
      FLARE intraoperative fluorescence imaging system after systemic injection of
      indocyanine green. Perfusion was also assessed using the standard of care by
      clinical observation and Doppler ultrasonography. NIR fluorescence perfusion
      assessment was confirmed by intermittent clamping of the vascular pedicle.
      RESULTS: NIR fluorescence imaging could identify bone perfusion at the cut end of
      the osteotomy site. When the vascular pedicle was clamped or ligated, NIR imaging
      demonstrated no fluorescence when injected with indocyanine green. With clamp
      removal, the osteotomy site emitted fluorescence, indicating bone perfusion. The
      results using fluorescence imaging showed 100% agreement with the clinical
      observation and Doppler findings. CONCLUSIONS: Vascularized bone transfers have
      become an important tool in reconstructive surgery; however, no established
      techniques are available to adequately assess perfusion. The results of our pilot
      study have indicated that NIR imaging can provide real-time, intraoperative
      assessment of bone perfusion.

PMID- 22664135
TI  - Generalization of geometrical flux maximizing flow on Riemannian manifolds for
      improved volumetric blood vessel segmentation.
AB  - Geometric flux maximizing flow (FLUX) is an active contour based method which
      evolves an initial surface to maximize the flux of a vector field on the surface.
      For blood vessel segmentation, the vector field is defined as the vectors
      specified by vascular edge strengths and orientations. Hence, the segmentation
      performance depends on the quality of the detected edge vector field. In this
      paper, we propose a new method for level set based segmentation of blood vessels
      by generalizing the FLUX on a Riemannian manifold (R-FLUX). We consider a 3D
      scalar image I(x) as a manifold embedded in the 4D space (x, I(x)) and compute
      the image metric by pullback from the 4D space, whose metric tensor depends on
      the vessel enhancing diffusion (VED) tensor. This allows us to devise a non
      linear filter which both projects and normalizes the original image gradient
      vectors under the inverse of local VED tensors. The filtered gradient vectors
      pertaining to the vessels are less sensitive to the local image contrast and more
      coherent with the local vessel orientation. The method has been applied to both
      synthetic and real TOF MRA data sets. Comparisons are made with the FLUX and
      vesselsness response based segmentations, indicating that the R-FLUX outperforms
      both methods in terms of leakage minimization and thiner vessel delineation.

PMID- 22664137
TI  - Persistence of double-stranded RNA in insect hemolymph as a potential determiner
      of RNA interference success: evidence from Manduca sexta and Blattella germanica.
AB  - RNA interference (RNAi) is a specific gene silencing mechanism mediated by double
      stranded RNA (dsRNA), which has been harnessed as a useful reverse genetics tool
      in insects. Unfortunately, however, this technology has been limited by the
      variable sensitivity of insect species to RNAi. We propose that rapid degradation
      of dsRNA in insect hemolymph could impede gene silencing by RNAi and
      experimentally investigate the dynamics of dsRNA persistence in two insects, the
      tobacco hornworm, Manduca sexta, a species in which experimental difficulty has
      been experienced with RNAi protocols and the German cockroach, Blattella
      germanica, which is known to be highly susceptible to experimental RNAi. An ex
      vivo assay revealed that dsRNA was rapidly degraded by an enzyme in M. sexta
      hemolymph plasma, whilst dsRNA persisted much longer in B. germanica plasma. A
      quantitative reverse transcription PCR-based assay revealed that dsRNA,
      accordingly, disappeared rapidly from M. sexta hemolymph in vivo. The M. sexta
      dsRNAse is inactivated by exposure to high temperature and is inhibited by EDTA.
      These findings lead us to propose that the rate of persistence of dsRNA in insect
      hemolymph (mediated by the action of one or more nucleases) could be an important
      factor in determining the susceptibility of insect species to RNAi.

PMID- 22664136
TI  - Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4
      methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats.
AB  - BACKGROUND: Reports from U.S., U.K. and European drug policy entities, and
      ongoing media accounts, show increasing recreational use of 4-methylmethcathinone
      (4-MMC, mephedrone) and 3,4-methylenedioxypyrovalerone (MDPV). Severe
      sympathomimetic symptoms, hallucinations, psychoses, and even deaths have been
      reported, yet little scientific information is available on the effects of these
      compounds in laboratory models. Available studies on the neurochemistry of these
      drugs show that 4-MMC and MDPV enhance DA neurotransmission, while 4-MMC
      additionally enhances 5-HT neurotransmission--a pattern much like that reported
      for methamphetamine versus 3,4-methylenedioxymethamphetamine (MDMA). As is the
      case for designer amphetamines, these neurochemical distinctions may predict
      differential potential for repetitive versus episodic abuse and distinct lasting
      toxicities. METHODS: This study determined relative locomotor stimulant effects
      of 4-MMC (1-10 mg/kg, s.c.) and MDPV (0.5-5.6 mg/kg, s.c.), in comparison with d
      methamphetamine (MA; 0.5-5.6 mg/kg, s.c.) and MDMA (1-7.5 mg/kg, s.c.) on a
      measure of locomotor activity--voluntary wheel running--in male Wistar rats
      (N=8). RESULTS: Compared to counts of wheel rotations after saline, a biphasic
      change in the pattern of counts was observed after injections of MA and MDPV,
      with relatively higher counts following lower doses and lower counts following
      the highest dose. However, monophasic, dose-dependent reductions in counts were
      observed in response to injections of MDMA and 4-MMC. CONCLUSION: Thus, voluntary
      wheel running yielded the same categorical distinctions for these drugs as did
      prior experiments testing the effects of these drugs on monoaminergic
      neurotransmission. These data indicate that MDPV produces prototypical locomotor
      stimulant effects whereas 4-MMC is more similar to the entactogen MDMA.

PMID- 22664138
TI  - CSF flow dynamics in motor neuron disease.
AB  - OBJECTIVE: To assess cerebrospinal fluid (CSF) flow dynamics involvement in the
      pathogenesis of amyotrophic lateral sclerosis (ALS), we conducted CSF flow
      studies on 40 individuals with motor neuron diseases (MNDs) including ALS, and 28
      age-matched normal and disease [cervical  spondylosis (CS)] controls. METHODS:
      The CSF pulsatile velocity anterior to the cervical cord at level C5 during one
      heart beat was determined non-invasively by phase-contrast electrocardiography
      triggered magnetic resonance imaging. RESULTS: In MND, caudal CSF velocity 
      peaked at 25% of the cardiac cycle after the R wave (UT(c)/RR), showing an
      increased delay in comparison to normal controls, while amplitude H(c) was
      significantly larger than that in CS. DISCUSSION: We conclude that CSF flow
      dynamics of MND  differ from those of controls and may thus facilitate
      differentiation of MND from CS.

PMID- 22664139
TI  - Hemispheric differences in VEPs to lateralised stimuli are a marker of recovery
      from neglect.
AB  - Visual-evoked potentials (VEPs) were recorded in seventeen patients with
      unilateral lesions of the right hemisphere (RH) and visuospatial neglect.
      Hemispheric differences were detected for VEP components in the time window from
      130 to 280 msec; this result replicates data from a previous study using a larger
      group of patients (Di Russo et al., 2008). Three patients were tested twice;
      their hemispheric differences, i.e., the differences in latency and amplitude of
      VEPs to ipsilesional and contralesional stimuli, were evaluated at the beginning
      and end of visuospatial rehabilitation training for neglect. The hemispheric
      differences were limited to components anterior N1 (N1a), posterior N1 (N1p) and
      P2 (not C1 and P1) and showed a significant decrease after training; amelioration
      at the behavioural level was also observed. Fourteen patients were tested only
      once, at different steps of their training. For the overall group, we determined
      the correlation between VEP hemispheric differences and the number of sessions
      attended by the patients at the time of VEP recording. The correlation was
      negative, the higher the number of sessions, the lower the hemispheric asymmetry,
      and high, ranging from .45 to .64, for both the latency and amplitude of the N1p
      and P2 components, and for the amplitude of the N1a component. The correlation
      between VEP hemispheric differences and time from onset (TFO) of the pathological
      event was not significant. Overall, the hemispheric differences between specific
      components of the VEP responses to lateralised stimuli appear to be a good marker
      of recovery from neglect.

PMID- 22664140
TI  - Phonology without semantics? Good enough for verbal short-term memory. Evidence
      from a patient with semantic dementia.
AB  - INTRODUCTION: There is considerable evidence that long-term knowledge has an
      influence on short-term memory (STM) performance. This reflects the activation of
      long-term representations involved in perceiving and comprehending spoken
      language. Still, this type of long-term knowledge might be of two different
      kinds. STM performance might be facilitated by information about the meaning of
      the word, or, alternatively, by familiarity with its phonological form. METHODS:
      We investigated these two alternatives by assessing word span in MC, a patient
      with semantic dementia. Four different lists of words were used: known words,
      words whose phonological form was known by the patient although she could not
      report its meaning, words that the patient did not recognize as words and judged
      as nonwords, nonwords. The patient's performance was compared to that of six
      matched controls. RESULTS: MC did not differ from controls in the first two types
      of lists and performed at the same level with both, while for words whose
      phonological form was unknown (and therefore not recognized as words) her
      performance was comparable to that with nonwords; also, with this type of item,
      she produced significantly more phonemic substitutions than controls.
      CONCLUSIONS: The results show that long-term knowledge facilitates immediate
      serial recall. However, this facilitation is due to familiarity with phonological
      representations rather than to knowledge of meaning.

PMID- 22664141
TI  - Disclosure of interest or conflict of interest?

PMID- 22664142
TI  - Microarray-based gene expression profiling reveals the mediators and pathways
      involved in the anti-arthritic activity of Celastrus-derived Celastrol.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic
      inflammation of the joints. The prolonged use of non-steroidal anti-inflammatory
      drugs and other newer drugs is associated with severe adverse reactions.
      Therefore, there is a need for newer anti-arthritic agents. Celastrol, a
      bioactive component of the Chinese herb Celastrus, possesses anti-arthritic
      activity as tested in the adjuvant arthritis (AA) model of rheumatoid arthritis
      (RA). However, the mechanism of action of Celastrol has not been fully defined.
      We reasoned that microarray analysis of the lymphoid cells of Celastrol-treated
      arthritic animals might provide vital clues in this regard. We isolated total RNA
      of the draining lymph node cells (LNCs) of Celastrol-treated (Tc) and vehicle
      treated (Tp) arthritic Lewis rats that were restimulated in vitro with the
      disease-related antigen, mycobacterial heat-shock protein 65 (Bhsp65), and tested
      it using microarray gene chips. Also tested was RNA from LNCs of control
      arthritic rats just before any treatment (T0). Seventy six genes involved in
      various biological functions were differentially regulated by Bhsp65 in LNCs of
      Tp group, and 19 genes among them were shared by the Tc group. Furthermore, a
      group of 14 genes was unique to Tc. When Tc and Tp were compared, many of the
      Bhsp65-induced genes were related to the immune cells, cellular proliferation and
      inflammatory responses. Our results revealed 10 differentially expressed genes
      and 14 pathways that constituted the "Celastrol Signature". Our results would
      help identify novel targets for RA therapy.

PMID- 22664143
TI  - The anti-inflammatory effects of the 5-HT3 receptor antagonist tropisetron are
      mediated by the inhibition of p38 MAPK activation in primary human monocytes.
AB  - BACKGROUND: There is evidence from human and animal research that 5
      hydroxytryptamine (5-HT) 3 receptor antagonists, particularly tropisetron, exert
      analgesic and anti-inflammatory activity. We have demonstrated that tropisetron
      inhibited lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)alpha
      and interleukin-(IL-)1beta release in primary human monocytes. The underlying
      mechanisms of these effects have not been investigated in detail so far. METHODS:
      The molecular mechanisms of the anti-inflammatory effects of tropisetron were
      investigated in human primary monocytes in vitro by studying IL-1beta and
      TNFalpha mRNA levels by PCR and reporter gene assay and by elucidating the
      phosphorylation of p38 mitogen activated kinase (MAPK) by Western blot. RESULTS:
      The steady state levels of IL-1beta and TNFalpha mRNA in LPS-activated human
      peripheral monocytes and the transcriptional activity of the TNFalpha promoter
      were not inhibited by tropisetron, suggesting that the inhibitory activity of
      this 5-HT3 receptor antagonist takes place at the post-transcriptional level.
      Additionally, we found that tropisetron prevents the phosphorylation and thus
      activation of the p38 MAPK, which is involved in post-transcriptional regulation
      of various cytokines. CONCLUSION: Our data indicate that the anti-inflammatory
      effects of the 5-HT3 receptor antagonist tropisetron, as shown in vivo, are
      possibly mediated by a selective inhibition of pro-inflammatory cytokines at the
      post-transcriptional level. 5-HT3 receptor antagonists are therefore a new and
      promising therapeutic option. New and more selective--in respect to the 5-HT3
      subtypes--5-HT3R antagonists might be a future perspective in the pharmacological
      treatment of inflammatory diseases.

PMID- 22664144
TI  - Structure-activity relationship of a guanine-free oligodeoxynucleotide as
      immunopotent inhibitor.
AB  - Excessive innate immune response could contribute to the pathogenesis of
      inflammatory and autoimmune diseases. It is required to develop agents to inhibit
      the overwhelming innate immune response. SAT05f, an inhibitory ODN with CCT
      repeat sequence found in human microsatellite DNA, has been demonstrated to down
      regulate TLR7/9-mediated innate immune response, protect mice from D-GalN/CpG ODN
      induced lethal shock, and reduce anti-ssDNA antibody level in the lupus-prone
      mice induced by chronic graft versus host disease (cGVHD). In this article, to
      explore the structure-activity relationship of SAT05f, we designed and
      synthesized a series of ODNs based on the sequence of SAT05f by changing repeat
      number of the CCT unit, substituting CCT unit with AAG at 3' end or 5' end or in
      the middle and by forming hairpin at 5' or 3' end, and tested their inhibitory
      effect on the CpG ODN induced proliferation and TNF-alpha production in murine
      immune cells. The results indicated that 1) at least 8 CCT units were required
      for a CCT repeat ODN to display its inhibitory activity; 2) CCT unit at 3' end of
      SAT05f was necessary for its full inhibitory activity; and 3) 5' end of SAT05f
      could be modified to design a more potent SAT05f derived inhibitory ODN. The data
      provided here would be helpful for finding a potent inhibitory ODN as a candidate
      medicament for the treatment of diseases associated with over-activated innate
      immune response.

PMID- 22664145
TI  - A supercritical CO2 extract from seabuckthorn leaves inhibits pro-inflammatory
      mediators via inhibition of mitogen activated protein kinase p38 and
      transcription factor nuclear factor-kappaB.
AB  - In the present study, we have demonstrated the anti-inflammatory properties of
      supercritical CO2 extract of seabuckthorn leaves (SCE) on mouse alveolar
      macrophage cell line (MH-S), human peripheral blood mononuclear cells (hPBMCs) in
      vitro and in-vivo. Treatment of MH-S cells with SCE (0.5-100 MUg/ml)
      significantly inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO)
      production. It also inhibited the release of LPS-induced pro-inflammatory
      cytokines IL-6 and TNF-alpha, which was further confirmed by suppression of LPS
      induced TNF-alpha in hPBMCs by ELISPOT assay. In addition, western blot analysis
      demonstrated that SCE decreased LPS-induced inducible nitric-oxide synthase
      (iNOS) and cyclooxygenase-2 (COX-2) protein expression in MH-S cells.
      Furthermore, SCE treatment also reduced nuclear factor-kappaB (NF-kappaB)
      translocation in nucleus induced by LPS in MH-S cells. To elucidate the molecular
      mechanism for inhibition of pro-inflammatory mediators by SCE (100 MUg/ml), we
      further studied the effect of SCE on LPS-induced p38 mitogen-activated protein
      kinase (MAPK). It was observed that the phosphorylation of p38 MAPK in LPS
      stimulated MH-S cells was significantly inhibited by SCE, which was further
      proven by suppression of LPS induced CD40 expression. The in-vivo model of AIA
      mice also showed a significant reduction in the inflammation of paw edema. These
      data collectively suggest that SCE suppressed the LPS-induced production of NO,
      IL-6, and TNF-alpha and expression of CD40, iNOS and COX-2 proteins by inhibiting
      NF-kappaB activation and phosphorylation of p38 MAPK. Hence, the SCE has potent
      anti-inflammatory activity and might be useful in chronic inflammatory diseases.

PMID- 22664146
TI  - Association of matrix metalloproteinases (MMP2, MMP7 and MMP9) genetic variants
      with left ventricular dysfunction in coronary artery disease patients.
AB  - BACKGROUND: Left ventricular dysfunction (LVD) is a condition resulting from
      clustered structural or functional cardiac disorder that reduces the ability of
      the ventricle to fill with or eject blood. The impaired ventricular function can
      be attributed to unfavorable ventricular remodeling. Among the pathways that
      contribute to remodeling process, matrix metalloproteinases (MMPs) appear to be
      of particular interest. We explored the association of MMP2 (C-735T, rs2285053),
      MMP7 (A-181G, rs11568818) and MMP9 (R279Q, rs17576), (P574R, rs2250889), (R668Q,
      rs17577) genetic variants with LVD in coronary artery disease (CAD) patients.
      METHODS: The study included 310 consecutive patients with angiographically
      confirmed CAD and 230 healthy controls. Among patients with CAD, 95 with reduced
      left ventricle ejection fraction (LVEF <= 45) were categorized as LVD.
      Polymorphisms were determined by PCR-RFLP. RESULTS: The MMP9 R668Q genetic
      variant was significantly associated with LVD (LVEF <= 45) (p value=0.009;
      OR=3.82). To validate our results, we performed a replication study in additional
      200 cases with similar clinical characteristics and results again confirmed
      consistent findings (p value=0.033; OR=3.59). Also the frequency of haplotype
      R,P,Q comprising R668Q variation in MMP 9 was significantly higher in reduced
      LVEF subjects (p value=0.008; OR=1.83). CONCLUSION: MMP9 R668Q plays important
      role in conferring susceptibility of LVD.

PMID- 22664147
TI  - Epigenetic biomarkers: A new perspective in laboratory diagnostics.
AB  - Epigenetics comprises the study of chemical modifications in the DNA and histones
      that regulates the gene expression or cellular phenotype. However, during the
      last decade this term has evolved after the elucidation of different mechanisms
      (microRNAs and nuclear organization of the chromosomes) involved in regulating
      gene expression. Epigenetics and the new designed technologies capable to analyze
      epigenetic changes (e.g., methylated DNA, miRNAs expression, post-translational
      modifications on histones among others) have disclosed an appealing scenario that
      will offer for the biomedical sciences new biomarkers for the study of
      neurodegenerative diseases, multifactorial complex diseases, rare diseases and
      cancer. Moreover, new technologies adapted for epigenetic studies will offer
      promising applications that in the next years will be common technologies in
      clinical laboratories. In this review we discuss epigenetic modifications used as
      possible biomarkers in several diseases. We also present the potential of
      methodologies to purify histones, and high throughput technologies as candidates
      to be set in clinical laboratories for their high potential analyzing epigenetic
      processes.

PMID- 22664148
TI  - Remote cerebellar hemorrhage following supratentorial craniotomy.
AB  - OBJECTIVE: Cerebellar hemorrhage remote from the site of surgery may complicate
      neurosurgical procedure. The exact pathophysiology of this type of hemorrhage is
      poorly understood. We retrospectively compared 16 patients who had remote
      cerebellar hemorrhage (RCH) with a case-matched  control cohort, to determine the
      significance of perisurgical and surgical factors that may predispose patients to
      such bleeding events. METHODS: From 1 June 2005 to 31 December 2008,
      postoperative routine head computed tomographic (CT) scan was performed in our
      institution and 16  patients with RCH after supratentorial neurosurgical
      procedure were identified. The medical charts of these 16 cases and a control
      cohort of 64 patients were recorded. All parameters were analyzed with regards to
      various variables. RESULTS: The incidence RCH after supratentorial  craniotomy
      increased after postoperative computed tomographic scan. The mechanism of
      cerebellar hemorrhage in this series of patients is most likely multifactorial.
      Several variables showed a significant association with the occurrence of RCH.
      Multivariate analysis indicated that the following  two factors independently
      correlated with occurrence of RCH: (1) postoperative epidural drainage amount;
      and (2) history of previous cerebrovascular accident (CVA) with cerebral atrophy.
      All cases with RCH underwent medical treatment and no neurological sequelae
      associated with RCH. CONCLUSIONS: Postoperative epidural drainage amount and
      history of previous CVA with cerebral atrophy can reliably predict the occurrence
      of cerebellar hemorrhage after supratentorial craniotomy. One of the most
      important strategies to minimize hazardous complications is to be aware of these
      potential  risk factors and to take action to prevent them.

PMID- 22664149
TI  - Staphylococcus aureus throat carriage is associated with ABO-/secretor status.
AB  - OBJECTIVES: In 30% of carriers, Staphylococcus aureus colonization affects
      exclusively the pharynx and occurs independently from its presence in the nares.
      This additional reservoir has implications for S. aureus transmission, infection,
      and decolonization. Host factors promoting colonization of the throat, however,
      are unknown. METHODS: We determined pharyngeal and persistent nasal carriage of
      S. aureus, ABO histo-blood group and ABH secretor status phenotypes in 227
      individuals. RESULTS: Compared to group A/non-secretors, group O/non-secretor
      individuals were at increased risk of carrying S. aureus in their throat (OR
      6.50, 95% confidence interval 1.28-33.03, P = 0.02) and group O/secretor
      individuals were protected (OR 0.24, 0.07-0.77, P = 0.02). Both associations
      became moderately stronger after adjusting for persistent S. aureus nasal
      carriage, which was found to be a risk factor for pharyngeal colonization in the
      univariable analysis (OR 2.41, 1.35-4.33, p = 0.003). Most simultaneous carriers
      (72%) had identical S. aureus genotypes in their nose and throat. CONCLUSIONS:
      These findings are consistent with in vitro studies that proposed a role of histo
      blood group antigens as ligands for S. aureus and support their contribution to
      the observed population variation in nasopharyngeal S. aureus colonization. Based
      on their tissue specific expression histo-blood group antigens appear to modulate
      individual S. aureus colonization patterns.

PMID- 22664150
TI  - Autopsy findings in late-onset Pompe disease: a case report and systematic review
      of the literature.
AB  - BACKGROUND: Late-onset Pompe disease (LOPD) is a rare cause of declining proximal
      muscle strength and respiratory function that can also affect other organ
      systems. The development of enzyme replacement therapy has made it one of the few
      inherited muscle disorders with treatment, but clinical response is difficult to
      assess due to the variable and often slow progression of illness. A better
      understanding of the disease's systemic effects can be gleaned through autopsy
      findings. PURPOSE: The purpose of this study was to: (1) describe the
      histological findings observed in LOPD, (2) provide correlations between reported
      histological and clinical findings, and (3) review the literature on autopsy
      findings in LOPD. METHODS: Histological evaluation of autopsy tissues from a 62
      year-old woman with LOPD was conducted. A clinical history was obtained by review
      of the medical records. The literature was reviewed for previously reported
      histological and clinical findings in LOPD. Based on this case report and
      information from prior publications, histological and clinical findings for the
      disease were correlated. RESULTS: Histologic examination revealed mostly mild
      vacuolar myopathy typical of glycogen accumulation within skeletal and smooth
      muscle cells. The most prominent vacuolar myopathy was in quadriceps muscle,
      which also exhibited chronic myositis with degenerating and regenerating muscle
      fibers. Transmission electron microscopy disclosed lysosomal glycogen
      accumulation within skeletal, cardiac, and vascular smooth muscle cells,
      correlating with published case reports of basilar artery and ascending aortic
      aneurysms and carotid artery dissection. Organs containing smooth muscle cells
      (the bladder, intestine, and esophagus) were also affected, explaining reports of
      symptoms such as urinary incontinence and dysphagia. In addition to glycogen
      accumulation, there was obvious damage to the contraction apparatus of myofibrils
      within cardiac and skeletal muscle cells. These histological and ultrastructural
      findings correlate with the clinical manifestations of LOPD. CONCLUSIONS: This
      study is the first to describe histological findings of LOPD utilizing both
      traditional paraffin-processed tissues and epoxy resin embedded tissues for high
      resolution light microscopy. The findings are similar to those seen in previous
      studies, but with improved morphological detail and glycogen preservation. This
      patient exhibited histological involvement of multiple organs, correlating with
      the clinical features of LOPD. With the advent of definitive therapy for Pompe
      disease, it is important to be aware of these findings and use them to develop
      methods for tracking therapeutic response.

PMID- 22664151
TI  - Pregnancy of a patient with multiple Acyl-CoA dehydrogenation deficiency (MADD).
AB  - We describe the pregnancy of a patient of French-Canadian descent with multiple
      Acyl-CoA dehydrogenation deficiency (MADD). The proband was found to harbor a
      previously reported homozygous missense mutation on EFTDH gene
      (p.Pro534Leu:c.1601C>T) confirming the biochemical diagnosis of MADD. This
      mutation was not found in 50 controls from the same ethnic background. The
      clinical and molecular information of all patients with ETFDH mutations reported
      in the literature up-to-date are summarized.

PMID- 22664153
TI  - Claudin expression profile separates Alzheimer's disease cases from normal aging
      and from vascular dementia cases.
AB  - We have reported earlier that tight-junction proteins are detectable by standard
      immunohistochemistry in the brain parenchyma, namely in the cell bodies of
      neurons, astrocytes, and oligodendrocytes. Here we show, by projection to latent
      structures - discriminate analysis (PLS-DA), that the immunohistochemical
      detection profile of tight junction proteins clearly distinguishes the AD cases
      from healthy aging controls and from the cases of dementia with a predominantly
      vascular pathology underlying the symptoms (vascular dementia, VaD; cerebral
      autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy, CADASIL; and cerebral amyloid angiopathy, CAA). Our findings
      might be valuable in the perspective of developing biomarkers for AD.

PMID- 22664154
TI  - Treatment patterns and associated costs with Parkinson's disease levodopa induced
      dyskinesia.
AB  - OBJECTIVES: This study examined the treatment patterns, direct healthcare costs
      and predictors of treatment costs associated with levodopa-induced dyskinesia
      (LID) in Parkinson's disease (PD). METHODS: This retrospective cohort study
      followed PD patients for 1-year pre- and post-onset of LID, using a large US
      health insurance claims database from January 1, 2004 to December 31, 2008.
      Patients with LID were matched to patients without LID based on propensity scores
      to control for potential selection bias. Descriptive statistics and bootstrap
      techniques were employed to assess patient demographic and clinical
      characteristics and costs incurred. Factors influencing treatment costs were
      analyzed using a generalized linear model with log-link function and gamma
      distribution. Costs were adjusted to 2009 prices. RESULTS: After patients
      developed LID, their total treatment costs were increased from $18,645 during the
      12 months preceding LID onset to $26,439 for the 12-month period subsequent to
      LID onset (incremental costs of $7795: P<0.001). PD-related costs increased from
      $3917 to $8110 (incremental costs of $4194: p<0.001) LID events, medical resource
      utilization, higher levodopa dosage, and use of alternative PD medications were
      associated with increases in total treatment costs. Few changes in medication
      treatment patterns were noted following the initial LID, with only slight
      increases in levodopa dosage and few additions of alternative agents.
      CONCLUSIONS: In the United States, PD patients with LID impose a significant
      economic burden when compared to patients without LID. Currently available,
      treatment strategies for dyskinesia should be used more frequently in PD
      management, and new treatment strategies should be considered as they may lower
      healthcare costs.

PMID- 22664155
TI  - Measurements of lenticulostriate arteries using 7T MRI: new imaging markers for
      subcortical vascular dementia.
AB  - Recent studies have demonstrated that ultra-high resolution MRA imaging using 7
      Tessla (T) MRI can be employed to noninvasively visualize the lenticulostriate
      arteries (LSA) that supply the basal ganglia and internal capsule. Subcortical
      vascular dementia (SVaD) is believed to involve these regions from an early
      stage. We investigated whether LSA abnormalities measured by 7T MRA correlate
      with MRI ischemia markers and neuropsychological/motor deficits. A total of 24
      subjects (12 with SVaD, 12 normal controls (NC)) were imaged with 3T and 7T MRIs.
      We assessed the severity of white matter hyperintensities (WMH) and the number of
      lacunes and microbleeds (MB) by visually inspecting images obtained from
      conventional 3T MRI. We also analyzed three-dimensional models of the measured
      LSAs obtained from 7T MRI. Compared to the NC, the SVaD subjects had fewer
      branches of LSAs and greater radii of LSAs. The number of branches was correlated
      with the number of lacunes. The number of branches was correlated with the
      delayed recall scores on Rey's Complex Figure Test (RCFT). While not quite
      reaching statistical significance, the immediate recall, recognition scores on
      the RCFT, recognition scores on the Seoul Verbal Learning Test, and the word and
      color readings of Stroop trended in the direction of correlation with the number
      of branches, as well as with the extrapyramidal scores. Our findings suggest that
      LSA imaging using 7T MRI might be a potent candidate for the detection of SVaD.

PMID- 22664156
TI  - Mutational and haplotype map of NOTCH3 in a cohort of Italian patients with
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL).
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL), the most common form of familial vascular
      dementia, is caused by mutations of the NOTCH3 gene. Approximately two hundred
      pathogenic mutations have been reported within five exons (exons 3, 4, 6, 11 and
      19) which accounted for 78% of known mutations in worldwide series. We reported
      twenty-one NOTCH3 pathogenic mutations (including five novel ones) identified in
      53 index Italian patients. Exons 4 (28%), 7 (21%) and 19 (24%) were the most
      frequently involved. To dissect genetic heterogeneity, we analyzed five
      haplotyped tagging single nucleotide polymorphisms (rs1044009, rs4809030,
      rs10426042, rs10423702 and rs3815188) in 95 patients, 39 unaffected pedigree
      members and 50 healthy controls. SNPs were analyzed using the Illumina VeraCode
      Universal Capture Beads technology by Allele Specific Primer Extension (ASPE). We
      identified ten different haplotypes named H1-H10; H1 was the most common
      haplotype in patients and controls and it was associated with at least twelve out
      of the twenty-one mutations. Detected mutations were not associated to specific
      haplotypes while genotyping was compatible with a possible founder effect for the
      novel p.S396C mutation which clustered in a restricted geographical area of
      northeast Italy. The results added on to the genetic heterogeneity of CADASIL and
      emphasized difficulties in designing algorithms for molecular diagnosis.

PMID- 22664157
TI  - An early sign of intraarticular fracture of the lateral tibial plateau during
      opening wedge high tibial osteotomy.
AB  - Intraarticular fracture of the lateral tibial plateau is one of the serious
      complications in medial opening wedge high tibial osteotomy (HTO). We present a
      case of fracture of the lateral tibial plateau during medial opening wedge HTO.
      The authors have found the early fracture sign, uneven divergence gap of proximal
      and distal parts during enlargement of the osteotomy site with a dilatator, a
      useful marker for early detection and prevention of fracture extending.

PMID- 22664159
TI  - Multiple-checkpoint inhibition of thymic stromal lymphopoietin-induced TH2
      response by TH17-related cytokines.
AB  - BACKGROUND: The interplay between allergy and autoimmunity has been a matter of
      long debate. Epidemiologic studies point to a decreased frequency of allergy in
      patients with autoimmune diseases. However, recent studies suggest that IL-17 and
      related cytokines, which play a central role in autoimmunity, might also promote
      allergy. OBJECTIVE: To address this controversy, we systematically studied the
      interactions between T(H)17-related cytokines and the thymic stromal
      lymphopoietin (TSLP)-mediated proallergic pathway. METHODS: We used human primary
      dendritic cells (DCs), T cells, and skin explants. A novel geometric
      representation and multivariate ANOVA were used to analyze the T(H) cytokine
      profile. RESULTS: We show that IL-17A specifically inhibits TSLP production but
      increases proinflammatory IL-8 production in human skin explants exposed to TNF
      alpha and IL-4. This inhibitory activity was confirmed in cultured skin explants
      of atopic dermatitis lesions. At the T-cell level, T(H)17-polarizing cytokines
      (IL-1beta, IL-6, TGF-beta, and IL-23) inhibited T(H)2 differentiation induced by
      TSLP-activated DCs. This led to a global dominance of a T(H)17-polarizing
      environment over TSLP-activated DCs, as revealed by clustering and computational
      analysis. CONCLUSIONS: Our data indicate that T(H)17-related cytokines are
      negative regulators of the TSLP immune pathway. This might explain the decreased
      frequency of allergy in patients with autoimmunity and suggests new means of
      manipulating proallergic responses.

PMID- 22664161
TI  - Human CD20+CD43+CD27+CD5- B cells generate antibodies to capsular polysaccharides
      of Streptococcus pneumoniae.

PMID- 22664162
TI  - Diagnosis and management of early asthma in preschool-aged children.
AB  - Asthma is a common disease in young children and is associated with significant
      morbidity and an increasing prevalence over time. Early childhood wheezing and
      asthma are heterogeneous disorders; thus identifying phenotypes of asthma remains
      a goal to identify high-risk children who might benefit from specific therapies
      or secondary prevention interventions. The typical pattern of illness in
      preschool-aged children consists of short but recurrent exacerbations of cough
      and wheeze usually triggered by viral respiratory tract infections. Documenting
      reversible airflow obstruction on lung function, allergen sensitization,
      increased IgE levels, or blood eosinophilia is helpful in establishing a
      diagnosis of asthma in preschool-aged children, if present; however, the
      diagnosis is most often based on symptom patterns, presence of risk factors, and
      therapeutic responses. The preschool-aged asthmatic population tends to be
      characterized as exacerbation prone with relatively limited impairment, unlike
      older children and adolescents who have more impairment-dominant disease.
      However, management of persistent disease is based largely on expert opinion and
      extrapolation from studies in older children given the relative lack of data in
      this age group. Strategies used to manage intermittent disease include daily and
      intermittent controller therapy. Management strategies for persistent asthma
      include daily inhaled corticosteroids, daily leukotriene receptor antagonists,
      and combination therapies. Finally, regular monitoring of symptom control and
      medication side effects is important along with titrating controllers to the
      minimally effective dose.

PMID- 22664163
TI  - Methylene blue-treated plasma: an increased allergy risk?

PMID- 22664164
TI  - Immunoglobulin replacement therapy: is there a role for IgA and IgM?

PMID- 22664165
TI  - Defining combined immunodeficiency.
AB  - BACKGROUND: Although the extreme condition of typical profound T-cell dysfunction
      (TD), severe combined immunodeficiency (SCID), has been carefully defined, we are
      currently in the process of better defining less typical T-cell deficiencies,
      which tend to present with autologous circulating T-cell combined
      immunodeficiency (CID). Because autologous cells might interfere with the outcome
      of bone marrow transplantation, protocols usually include conditioning regimens.
      Therefore it is important to define the numbers of autologous cells usually
      detected in patients with CID versus those with SCID. OBJECTIVES: We sought to
      determine the number of circulating T cells in patients with SCID as opposed to
      those with CID, to study their function, and to evaluate their possible detection
      during newborn screening using T-cell receptor excision circle (TREC) analysis.
      METHODS: Numbers of circulating CD3(+) T cells (as determined by means of flow
      cytometry), in vitro responses to PHA, and TREC levels, all measured at
      presentation, were compiled from the research charts of the entire cohort of
      patients followed prospectively for T-cell immunodeficiency at the Hospital for
      Sick Children. Clinical data were ascertained retrospectively from the patient's
      hospital charts. RESULTS: One hundred three patients had CD3(+) determinations,
      and 80 of them had a genetic diagnosis. All patients considered to have typical
      SCID had CD3(+) T-cell counts of fewer than 500 cells/MUL. Some variability was
      observed among different genotypes. In vitro responses to PHA were recorded in 88
      patients, of whom 68 had a genetic diagnosis. All patients with low CD3(+) T-cell
      numbers (<500 cells/MUL) also had markedly decreased responses to PHA (typical
      SCIDs). However, responses ranged widely in the groups of patients with TD who
      had more than 500 CD3(+) autologous circulating T cells per microliter. Although
      patients with Omenn syndrome and zeta chain-associated protein, 70 kDa (ZAP70),
      and purine nucleoside phosphorylase (PNP) deficiencies had low responses,
      patients with the p.R222C mutation in the IL-2 receptor gamma(IL2RG) gene as well
      as IL-10 receptor and CD40 ligand deficiencies had normal or near-normal mitogen
      responses. Finally, 51 patients had TREC levels measured. All patients with
      typical SCID, Omenn syndrome, and ZAP70 deficiency had low TREC levels. In
      contrast, patients with mutations in forkhead box protein 3 (FOXP3), CD40 ligand
      (CD40L), and IL-10 receptor alpha(IL10RA), as well as patients with the p.R222C
      mutation in the IL2RG gene, had normal TREC levels. CONCLUSION: Patients with
      typical SCID can be defined as having fewer than 500 circulating CD3(+) T cells.
      Most patients with autologous T cells still have profound TD, as defined by
      reduced in vitro function and thymus output. Some patients with conditions
      including TD have normal TREC levels and will therefore not be detected in a TREC
      based newborn screening program.

PMID- 22664166
TI  - Epoxyeicosatrienoic acids are involved in the C(70) fullerene derivative-induced
      control of allergic asthma.
AB  - BACKGROUND: Fullerenes are molecules being investigated for a wide range of
      therapeutic applications. We have shown previously that certain fullerene
      derivatives (FDs) inhibit mast cell (MC) function in vitro, and here we examine
      their in vivo therapeutic effect on asthma, a disease in which MCs play a
      predominant role. OBJECTIVE: We sought to determine whether an efficient MC
      stabilizing FD (C(70)-tetraglycolate [TGA]) can inhibit asthma pathogenesis in
      vivo and to examine its in vivo mechanism of action. METHODS: Asthma was induced
      in mice, and animals were treated intranasally with TGA either simultaneously
      with treatment or after induction of pathogenesis. The efficacy of TGA was
      determined through the measurement of airway inflammation, bronchoconstriction,
      serum IgE levels, and bronchoalveolar lavage fluid cytokine and eicosanoid
      levels. RESULTS: We found that TGA-treated mice have significantly reduced airway
      inflammation, eosinophilia, and bronchoconstriction. The TGA treatments are
      effective, even when given after disease is established. Moreover, we report a
      novel inhibitory mechanism because TGA stimulates the production of an anti
      inflammatory P-450 eicosanoid metabolites (cis-epoxyeicosatrienoic acids [EETs])
      in the lung. Inhibitors of these anti-inflammatory EETs reversed TGA inhibition.
      In human lung MCs incubated with TGA, there was a significant upregulation of
      CYP1B gene expression, and TGA also reduced IgE production from B cells. Lastly,
      MCs incubated with EET and challenged through FcepsilonRI had a significant
      blunting of mediator release compared with nontreated cells. CONCLUSION: The
      inhibitory capabilities of TGA reported here suggest that FDs might be used a
      platform for developing treatments for asthma.

PMID- 22664168
TI  - Association of poor insight in schizophrenia with structure and function of
      cortical midline structures and frontopolar cortex.
AB  - BACKGROUND: Poor insight is a central characteristic of psychosis and
      schizophrenia. Accumulating evidence indicates that cortical midline structures
      (CMS) and frontopolar cortex (FPC), both of which are associated with insight
      related processing in healthy subjects, are among the most affected brain
      structures in schizophrenia. However, the hypothesis that direct associations
      between function of these brain regions and poor insight in schizophrenia exist
      has not been tested previously. METHODS: We studied 21 patients with
      schizophrenia and 17 healthy control subjects with structural and functional
      magnetic resonance imaging during a clinical insight task and a comparable
      control task. We assessed the level of insight, depression, positive and negative
      symptoms, and neurocognitive function, then adjusted correlation between insight
      and insight-task-related brain activation for potential confounders. Voxel-based
      morphometry was used to compare brain volumes between groups. RESULTS: Insight
      correlated strongly with the activation of the CMS and the FPC during the
      clinical insight tasks, independently of potential confounders. The CMS
      activation was stronger during the insight task than during the control task in
      patients. The functional correlates of insight matched the distribution of
      cortical volume reduction in the patient group. CONCLUSIONS: These findings
      suggest a link between known regional brain abnormalities and the manifestation
      of poor insight in schizophrenia. The contribution of CMS to insight may be
      related to self-referential processing and that of FPC to the integration of
      multiple cognitive processes that are necessary for accurate evaluation of one's
      mental illness.

PMID- 22664167
TI  - Alternaria alternata allergen Alt a 1: a unique beta-barrel protein dimer found
      exclusively in fungi.
AB  - BACKGROUND: Alternaria species is one of the most common molds associated with
      allergic diseases, and 80% of Alternaria species-sensitive patients produce IgE
      antibodies to a major protein allergen, Alt a 1. The structure and function of
      Alt a 1 is unknown. OBJECTIVE: We sought to obtain a high-resolution structure of
      Alt a 1 using x-ray crystallography and to investigate structural relationships
      between Alt a 1 and other allergens and proteins reported in the Protein Data
      Bank. METHODS: X-ray crystallography was used to determine the structure of Alt a
      1 by using a custom-designed set of crystallization conditions. An initial Alt a
      1 model was determined by the application of a Ta(6)Br(12)(2+) cluster and single
      wavelength anomalous diffraction. Bioinformatic analyses were used to compare the
      Alt a 1 sequence and structure with that of other proteins. RESULTS: Alt a 1 is a
      unique beta-barrel comprising 11 beta-strands and forms a "butterfly-like" dimer
      linked by a single disulfide bond with a large (1345 A(2)) dimer interface.
      Intramolecular disulfide bonds are conserved among Alt a 1 homologs. Currently,
      the Alt a 1 structure has no equivalent in the Protein Data Bank. Bioinformatics
      analyses suggest that the structure is found exclusively in fungi. Four
      previously reported putative IgE-binding peptides have been located on the Alt a
      1 structure. CONCLUSIONS: Alt a 1 has a unique, dimeric beta-barrel structure
      that appears to define a new protein family with unknown function found
      exclusively in fungi. The location of IgE antibody-binding epitopes is in
      agreement with the structural analysis of Alt a 1. The Alt a 1 structure will
      allow mechanistic structure/function studies and immunologic studies directed
      toward new forms of immunotherapy for Alternaria species-sensitive allergic
      patients.

PMID- 22664170
TI  - Handwashing against hospitalization for influenza: time for PHIR?

PMID- 22664169
TI  - Premorbid multivariate markers of neurodevelopmental instability in the
      prediction of adult schizophrenia-spectrum disorder: a high-risk prospective
      investigation.
AB  - The authors examined whether multiple childhood indicators of neurodevelopmental
      instability known to relate to schizophrenia-spectrum disorders could predict
      later schizophrenia-spectrum outcomes. A standardized battery of neurological and
      intellectual assessments was administered to a sample of 265 Danish children in
      1972, when participants were 10-13 years old. Parent psychiatric diagnoses were
      also obtained in order to evaluate the predictive strength of neurodevelopmental
      factors in combination with genetic risk. Adult diagnostic information was
      available for 244 members of the sample. Participants were grouped into three
      categories indicating level of genetic risk: children with a parent with
      schizophrenia (n=94); children with a parent with a non-psychotic mental health
      diagnosis (n=84); and children with a parent with no records of psychiatric
      hospitalization (n=66). Variables measured included minor physical anomalies
      (MPAs), coordination, ocular alignment, laterality, and IQ. Adult diagnoses were
      assessed through psychiatric interviews in 1992, as well as through a scan of the
      national psychiatric registry through 2007. Through a combination of multiple
      childhood predictors, the model correctly classified 73% (24 of 33) of the
      participants who eventually developed a schizophrenia-spectrum outcome in
      adulthood. Results suggest that, with replication, multivariate premorbid
      prediction could potentially be a useful complementary approach to identifying
      individuals at risk for developing a schizophrenia-spectrum disorder. Genetic
      risk, MPAs, and other markers of neurodevelopmental instability may be useful for
      comprehensive prediction models.

PMID- 22664171
TI  - Characterization and virulence of Beauveria spp. recovered from emerald ash borer
      in southwestern Ontario, Canada.
AB  - The emerald ash borer (EAB), Agrilus planipennis (Coleoptera: Buprestidae), is an
      invasive wood boring beetle that is decimating North America's ash trees
      (Fraxinus spp.). To find effective and safe indigenous biocontrol agents to
      manage EAB, we conducted a survey in 2008-2009 of entomopathogenic fungi (EPF)
      infecting EAB in five outbreak sites in southwestern Ontario, Canada. A total of
      78 Beauveria spp. isolates were retrieved from dead and mycosed EAB cadavers
      residing in the phloem tissues of dead ash barks, larval frass extracted from
      feeding galleries under the bark of dead trees. Molecular characterization using
      sequences of the ITS, 5' end of EF1-alpha and intergenic Bloc region fragments
      revealed that Beauveria bassiana and Beauveria pseudobassiana were commonly
      associated with EAB in the sampled sites. Based on phylogenetic analysis inferred
      from ITS sequences, 17 of these isolates clustered with B. bassiana, which
      further grouped into three different sub-clades. However, the combined EF1-alpha
      and Bloc sequences detected five genotypes among the three sub-clades. The
      remaining 61 isolates clustered with B. pseudobassiana, which had identical ITS
      sequences but were further subdivided into two genotypes by variation in the EF1
      alpha and Bloc regions. Initial virulence screening against EAB adults of 23
      isolates representing the different clades yielded 8 that produced more than 90%
      mortality in a single concentration assay. These isolates differed in virulence
      based on LC(50) values estimated from multiple concentration bioassay and based
      on mean survival times at a conidia concentration of 2*10(6) conidia/ml. B.
      bassiana isolate L49-1AA was significantly more virulent and produced more
      conidia on EAB cadavers compared to the other indigenous isolates and the
      commercial strain B. bassiana GHA suggesting that L49-1AA may have potential as a
      microbiological control agent against EAB.

PMID- 22664172
TI  - Characteristics and prognostic value of acute catecholamine surge in patients
      with aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVES: The characteristics of serum catecholamine concentration at the hyper
      acute phase of aneurysmal subarachnoid hemorrhage (SAH) and its relationship
      between patient outcome and delayed vasospasm were investigated. METHODS:
      Patients with aneurysmal SAH (170) were prospectively studied between August 2008
      and June 2011. Baseline demographic data and physiological parameters, including
      plasma concentrations of adrenaline (AD), noradrenaline (NA), and dopamine (DP)
      were evaluated for all patients. RESULTS: On admission, plasma AD, NA, and DP
      levels were significantly higher in patients with a poor clinical grade on
      admission (Hunt and Kosnik grade: IV-V), compared to those with a good clinical
      grade on admission (Hunt and Kosnik grade: I-III). AD showed a markedly high
      concentration immediately after the onset of SAH and then rapidly decreased. NA
      levels peaked within 6 hours after onset, then significantly decreased. The
      increase of DP with time was not significant, but showed a similar trend to that
      of NA. The level of each catecholamine showed significant mutual correlation. Our
      multivariate model demonstrated that age, poor clinical grade at admission,
      plasma AD and NA levels were good predictors of poor patient outcome [receiver
      operating characteristic (ROC) area: 0.83]. And that poor clinical grade at
      admission, Fisher scale, blood sugar level and plasma AD level were good
      predictors of the development of delayed vasospasm (ROC area: 0.81) (1.3).
      CONCLUSIONS: The present findings suggest that sympathetic activation in patients
      in the acute phase of SAH reflects the severity of SAH, and is closely related to
      the development of delayed vasospasm, leading to the subsequent immune response
      and inflammatory reactions. Strategies for suppressing catecholamine at the hyper
      acute phase may contribute to vasospasm prevention and improve patient outcome.

PMID- 22664173
TI  - Extracellular matrix protein mediated regulation of the osteoblast
      differentiation of bone marrow derived human mesenchymal stem cells.
AB  - The biomimetic approach of tissue engineering exploits the favorable properties
      of the extracellular matrix (ECM), to achieve better scaffold performance and
      tissue regeneration. ECM proteins regulate cell adhesion and differentiation
      through integrin mediated signal transduction. In the present study, we have
      examined the role of ECM proteins such as collagen type I, fibronectin, laminin
      and vitronectin in regulating the proliferation and osteogenic differentiation of
      bone marrow derived human mesenchymal stem cells (hMSCs). hMSCs were grown on
      selected ECM protein treated tissue culture plates. The growth kinetics was
      assessed by calculating the doubling time of the cells on different ECM treated
      plates. The cells were directed to osteoblast lineage by growing them in
      osteogenic induction media for 21 day. Differentiation was evaluated at different
      time points by osteoblast differentiation associated gene expression, alkaline
      phosphatase (ALP) activity, histochemical staining for mineralized matrix and
      calcium quantification. The doubling time of hMSCs cultured on collagen type I
      was significantly low, which was followed by laminin and fibronectin treated
      plates. However, doubling time of hMSCs cultured on vitronectin treated plate was
      not significantly different than that of the untreated control. High ALP gene
      (ALPL) expression and associated enhancement of mineralization were observed on
      collagen type I, fibronectin and vitronectin treated plates. Collagen type I
      showed early onset of mineralization with high ALP activity and up-regulation of
      osteopontin, ALPL, bone sialoprotein and osteocalcin genes. Vitronectin also up
      regulated these genes and showed the highest amount of calcium in the secreted
      mineral matrix. Therefore, we conclude that, ECM proteins indeed modified the
      growth patterns and induced the osteoblast differentiation of hMSCs. Our findings
      have significant implication for bone tissue engineering applications.

PMID- 22664174
TI  - Normal and abnormal development of the cardiac conduction system; implications
      for conduction and rhythm disorders in the child and adult.
AB  - The cardiac conduction system is a specialized network that initiates and closely
      coordinates the heart beat. Cardiac conduction system development is intricately
      related to the development and maturation of the embryonic heart towards its four
      chambered form, as is indicated by the fact that disturbed development of cardiac
      structures is often accompanied by a disturbed formation of the CCS.
      Electrophysiological studies have shown that selected conduction disturbances and
      cardiac arrhythmias do not take place randomly in the heart but rather at
      anatomical predilection sites. Knowledge on development of the CCS may facilitate
      understanding of the etiology of arrhythmogenic events. In this review we will
      focus on embryonic development of the CCS in relation to clinical arrhythmias, as
      well as on specific cardiac conduction abnormalities that are observed in
      patients with congenital heart disease.

PMID- 22664175
TI  - Mesodermal expression of Fgfr2S252W is necessary and sufficient to induce
      craniosynostosis in a mouse model of Apert syndrome.
AB  - Coordinated growth of the skull and brain are vital to normal human development.
      Craniosynostosis, the premature fusion of the calvarial bones of the skull, is a
      relatively common pediatric disease, occurring in 1 in 2500 births, and requires
      significant surgical management, especially in syndromic cases. Syndromic
      craniosynostosis is caused by a variety of genetic lesions, most commonly by
      activating mutations of FGFRs 1-3, and inactivating mutations of TWIST1. In a
      mouse model of TWIST1 haploinsufficiency, cell mixing between the neural crest
      derived frontal bone and mesoderm-derived parietal bone accompanies coronal
      suture fusion during embryonic development. However, the relevance of lineage
      mixing in craniosynostosis induced by activating FGFR mutations is unknown. Here,
      we demonstrate a novel mechanism of suture fusion in the Apert Fgfr2(S252W) mouse
      model. Using Cre/lox recombination we simultaneously induce expression of
      Fgfr2(S252W) and beta-galactosidase in either the neural crest or mesoderm of the
      skull. We show that mutation of the mesoderm alone is necessary and sufficient to
      cause craniosynostosis, while mutation of the neural crest is neither. The
      lineage border is not disrupted by aberrant cell migration during fusion.
      Instead, the suture mesenchyme itself remains intact and is induced to undergo
      osteogenesis. We eliminate postulated roles for dura mater or skull base changes
      in craniosynostosis. The viability of conditionally mutant mice also allows post
      natal assessment of other aspects of Apert syndrome.

PMID- 22664177
TI  - Conservative management and resolution of iatrogenic type A aortic dissection in
      a patient with previous cardiac surgery.

PMID- 22664176
TI  - RNA-Seq defines novel genes, RNA processing patterns and enhancer maps for the
      early stages of nephrogenesis: Hox supergenes.
AB  - During kidney development the cap mesenchyme progenitor cells both self renew and
      differentiate into nephrons. The balance between renewal and differentiation
      determines the final nephron count, which is of considerable medical importance.
      An important goal is to create a precise genetic definition of the early
      differentiation of cap mesenchyme progenitors. We used RNA-Seq to transcriptional
      profile the cap mesenchyme progenitors and their first epithelial derivative, the
      renal vesicles. The results provide a global view of the changing gene expression
      program during this key period, defining expression levels for all transcription
      factors, growth factors, and receptors. The RNA-Seq was performed using two
      different biochemistries, with one examining only polyadenylated RNA and the
      other total RNA. This allowed the analysis of noncanonical transcripts, which for
      many genes were more abundant than standard exonic RNAs. Since a large fraction
      of enhancers are now known to be transcribed the results also provide global maps
      of potential enhancers. Further, the RNA-Seq data defined hundreds of novel
      splice patterns and large numbers of new genes. Particularly striking was the
      extensive sense/antisense transcription and changing RNA processing complexities
      of the Hox clusters.

PMID- 22664178
TI  - The natural history of moderate aortic stenosis in a veteran population.
AB  - OBJECTIVE: Our objective was to evaluate the natural history of moderate aortic
      stenosis in veterans--a unique patient population with significant comorbidities.
      METHODS: We retrospectively reviewed the records of all patients who underwent
      echocardiography at a single veterans affairs hospital during 2006. We identified
      consecutive patients who had moderate aortic stenosis as indicated by a mean
      transaortic gradient of 25 to 40 mm Hg, peak aortic jet velocity of 3 to 4 m/s,
      or aortic valve area of 1.0 to 1.5 cm(2). The primary end point was defined as
      survival without aortic valve replacement. RESULTS: Of the 104 patients (mean
      age, 74 +/- 10 years), 49% had diabetes, 21% had peripheral vascular disease, 21%
      were current smokers, 18% had chronic obstructive pulmonary disease, 60% had
      coronary artery disease, 89% had hypertension, and 31% had a body mass index of
      30 kg/m(2) or more. Mean ejection fraction was 49% +/- 12%. During the mean
      follow-up period of 22 months (range, 1-67 months), 30% of patients underwent
      aortic valve replacement--26% for symptomatic severe aortic stenosis and 4%
      concomitantly with coronary artery bypass grafting as the primary indicated
      operation--and 61% died. Event-free survivals were 48%, 24%, and 15% at 1, 3, and
      5 years, respectively. CONCLUSIONS: Our cohort of military veteran patients had
      significant comorbidities. Event-free survival for such patients who have
      moderate aortic stenosis is significantly lower than previously reported data
      suggest. Within this unique group of patients, identifying factors that
      accelerate the progression of moderate aortic stenosis would help surgeons select
      patients who may benefit from early aortic valve replacement for moderate aortic
      stenosis.

PMID- 22664179
TI  - Giant vein graft pseudoaneurysm with pulmonary hemorrhage.

PMID- 22664180
TI  - Sequence-independent VIDISCA-454 technique to discover new viruses in canine
      livers.
AB  - In many mammals, viruses cause hepatitis. Despite many efforts a specific virus
      responsible for canine idiopathic hepatitis has not been identified. The
      discovery of a viral etiology in canine hepatitis will promote the development of
      specific drugs and vaccines for the treatment of idiopathic hepatitis in dogs.
      The objective of this study was the application of the sequence-independent Virus
      Discovery cDNA-amplified fragment length polymorphism (VIDISCA) technique
      combined with high through-put sequencing on a Roche-454 sequencer to identify
      unknown viruses. Liver tissue of a dog with idiopathic acute hepatitis was
      cultured on a canine liver cell line and the cell culture medium was submitted to
      the VIDISCA-454 technique. Without prior knowledge of the viral species involved,
      this technique identified Canine adenovirus type 1 (CAV-1) as the infecting
      agent. This demonstrates the power of VIDISCA-454 to identify viruses,
      independent of preliminary information about the genomic sequence. Consequently,
      the strategy of propagation in this cell line followed by the VIDISCA-454
      technique is valuable to identify the viral etiology of idiopathic hepatitis in
      dogs.

PMID- 22664181
TI  - A straightforward genotyping of the relevant IL28B SNPs for the prediction of
      hepatitis C treatment outcome.
AB  - A sustained virological response is not achieved by a significant proportion of
      chronic hepatitis C patients treated with interferon-based regimens. Due to the
      associated side effects and high costs, therapy response markers have been
      thoroughly sought. Two Single Nucleotide Polymorphisms (SNPs), rs12979860 and
      rs8099917, which are located upstream from the IL28B gene, have been remarkably
      described to have a strong association with treatment efficacy. The aim of this
      study was to develop a straightforward method for genotyping such polymorphisms.
      A Polymerase Chain Reaction (PCR) followed by enzymatic restriction of amplicons
      was established for SNPs genotyping. Online computation resources were employed
      for retrieving reference sequences, such as the selection of oligonucleotides and
      restriction enzymes. Two pairs of primers were designed and validated for the
      amplification of segments encompassing rs12979860 (694bp) and rs8099917 (496bp)
      with common thermocycling parameters. The endonucleases Hpy166II and BsrDI were
      selected and used for allelic discrimination related to rs12979860 (C/T) and
      rs8099917 (T/G), respectively. The expected electropherotypes were confirmed for
      all possible genotypes in 75 blood samples. In addition, the results were
      validated by sequencing. The method constitutes a simple and reliable assay,
      which may be readily available for genotyping of rs12979860 and rs8099917 in
      laboratories that support hepatitis C treatment centers.

PMID- 22664182
TI  - Recombinant ELISA using baculovirus-expressed VP2 for detection of antibodies
      against canine parvovirus.
AB  - The gene encoding the VP2 protein of canine parvovirus type 2 was expressed in an
      insect-baculovirus system. The recombinant (r) VP2 was similar
      antigenically/functionally to the native capsid protein as demonstrated by
      hemagglutination, Western blotting and hemagglutination inhibition test, using
      Canine parvovirus type-2 (CPV-2) positive sera. An enzyme-linked immunosorbent
      assay (ELISA) using the rVP2 was used for testing CPV-2 positive and negative
      sera from dogs and for determining the threshold of maternally derived antibodies
      interfering with successful vaccination of pups against CPV-2.

PMID- 22664183
TI  - A new method for quantifying white spot syndrome virus: Experimental challenge
      dose using TaqMan real-time PCR assay.
AB  - White spot syndrome virus (WSSV) is an important pathogen in shrimp aquaculture.
      The susceptibility of crayfish (Procambarus clarkii) was assessed by means of
      serial dilutions of a solution containing WSSV. A TaqMan real-time PCR was used
      to quantify the WSSV challenge dose in P. clarkii. The results showed that WSSV
      copies could be detected at concentrations from 1.365*10(4) to 1.129*10(9)
      copies/MUl. The viral infectivity (LD(50)), measured as the mortality of infected
      crayfish, indicated 60% mortality in the 10(5) dilution group (1.524*10(5)
      copies/MUl). TaqMan real-time PCR represents a novel standard method, based on
      the by quantitation of WSSV copies, for determining the appropriate concentration
      of WSSV for use in infection experiments.

PMID- 22664185
TI  - Multiplex RT-PCR assay for differentiating European swine influenza virus
      subtypes H1N1, H1N2 and H3N2.
AB  - In Europe, three major swine influenza viral (SIV) subtypes (H1N1, H1N2 and H3N2)
      have been isolated in pigs. Developing a test that is able to detect and identify
      the subtype of the circulating strain rapidly during an outbreak of respiratory
      disease in the pig population is of essential importance. This study describes
      two multiplex RT-PCRs which distinguish the haemagglutinin (HA) gene and the
      neuraminidase (NA) gene of the three major subtypes of SIV circulating in Europe.
      The HA PCR was able to identify the lineage (avian or human) of the HA of H1
      subtypes. The analytical sensitivity of the test, considered to be unique, was
      assessed using three reference viruses. The detection limit corresponded to 1*10(
      1) TCID(50)/200MUl for avian-like H1N1, 1*10(0) TCID(50)/200MUl for human-like
      H1N2 and 1*10(1) TCID(50)/200MUl for H3N2 SIV. The multiplex RT-PCR was first
      carried out on a collection of 70 isolated viruses showing 100% specificity and
      then on clinical samples, from which viruses had previously been isolated,
      resulting in an 89% positive specificity of the viral subtype. Finally, the test
      was able to identify the viral subtype correctly in 56% of influenza A positive
      samples, from which SIV had not been isolated previously. It was also possible to
      identify mixed viral infections and the circulation of a reassortant strain
      before performing genomic studies.

PMID- 22664186
TI  - Guiding authors to reliably use taxonomic names.

PMID- 22664184
TI  - Patterns of cellular and HPV 16 methylation as biomarkers for cervical neoplasia.
AB  - Aberrant promoter methylation of biologically relevant genes in cervical cancer
      and uneven CpG distribution within the human papillomavirus 16 (HPV 16) enhancer
      region have been reported. Cervical samples and questionnaires from 151 women
      screened for cervical cancer in Appalachian Ohio were analyzed. Methylation was
      measured by bisulfite sequencing in candidate gene sites in ESR1, DCC, p16, and
      LINE1 elements. Among 89 HPV 16-positive women, CpG sites in the E6 promoter and
      enhancer regions and the L1 region of the HPV 16 genome were measured.
      Methylation levels were compared by cervical cytology and HPV 16 status. HPV
      methylation was low regardless of cytology status, however E6 methylation was
      significantly higher in women with normal cytology. ESR1 and DCC methylation were
      significantly higher in HPV 16-positive women. Increased methylation at sites in
      the E6 promoter region was associated with lower odds of abnormal cytology.
      Increased methylation in candidate genes was associated with higher odds of
      abnormal cytology, particularly DCC region 2.4, DCC region 2.6, ESR1 region 3.2,
      and LINE1 site 1.2. HPV 16 genome CpG methylation was low except for the L1
      region. In general, lower HPV 16 methylation and higher candidate gene
      methylation levels were associated with higher odds of abnormal cytology.

PMID- 22664187
TI  - Spectral editing based on scalar spin-spin interactions: new results on the
      structure of metathiophosphate glasses.
AB  - The local structure of glassy NaPS(3) and AgPS(3) was analyzed based on
      quantitative (31)P MAS-NMR spectroscopy. The glasses contain some oxide
      impurities, which could be quantified from the NMR spectral analysis. Four
      discrete resonances are observed in both glasses, which were assigned to four
      distinct types of phosphate groups P((n)), where n is the number of P-S-P
      bridges(i.e., P((0)), P((1)), P((2)), and P((3)) units, respectively) with the
      help of 2D homonuclear J-resolved and INADEQUATE methods. Based on the results
      obtained, the interpretations of previous spectra obtained at low spinning speeds
      on lithium and silver thiophosphate glasses (Chem. Mater. 2 (1990), 273, and J.
      Am. Chem. Soc. 114 (1992), 5775) need to be revised. Contrary to the situation in
      alkali phosphate glasses, the corresponding sulfide analogs are characterized by
      a wide P((n)) species distribution close to that predicted by a statistical
      charge distribution. INADEQUATE experiments fail to detect P((n))-P((n-1))
      connectivities, suggesting that the structure of these glasses is rather
      inhomogeneous, possibly featuring the different P((n)) species in segregated
      domains.

PMID- 22664188
TI  - Discovery of novel 5-(ethyl or hydroxymethyl) analogs of 2'-'up' fluoro (or
      hydroxyl) pyrimidine nucleosides as a new class of Mycobacterium tuberculosis,
      Mycobacterium bovis and Mycobacterium avium inhibitors.
AB  - Discovery of novel antimycobacterial compounds that work on distinctive targets
      and by diverse mechanisms of action is urgently required for the treatment of
      mycobacterial infections due to the emerging global health threat of
      tuberculosis. We have identified a new class of 5-ethyl or hydroxy (or methoxy)
      methyl-substituted pyrimidine nucleosides as potent inhibitors of Mycobacterium
      bovis, Mycobacterium tuberculosis (H37Ra, H37Rv) and Mycobacterium avium. A
      series of 2'-'up' fluoro (or hydroxy) nucleosides (1, 2, 4-6, 9, 10, 13, 16, 18,
      21, 24) was synthesized and evaluated for antimycobacterial activity. Among 2'
      fluorinated compounds, 1-(3-bromo-2,3-dideoxy-2-fluoro-beta-d-arabinofuranosyl)-5
      ethyluracil (13) exhibited promising activity against M. bovis and Mtb alone, and
      showed synergism when combined with isoniazid. The most active compound emerging
      from these studies, 1-(beta-d-arabinofuranosyl)-4-thio-5-hydroxymethyluracil (21)
      inhibited Mtb (H37Ra) (MIC(50)=0.5 MUg/mL) and M. bovis (MIC(50)=0.5 MUg/mL) at
      low concentrations, and was ten times more potent against Mtb (H37Ra) than
      cycloserine (MIC(50)=5.0 MUg/mL), a second line drug. It also showed an additive
      effect when combined with isoniazid. Compound 21 retained sensitivity against a
      rifampicin-resistant (H37Rv) strain of Mtb (MIC(50)=1 MUg/mL) at concentrations
      similar to that for a rifampicin-sensitive (H37Rv) strain, suggesting that it has
      no cross-resistance to a first-line anti-TB drug. In addition, the replication of
      M. avium was also inhibited by 21 (MIC(50)=10 MUg/mL). No cellular toxicity of 13
      or 21 was observed up to the highest concentration tested (CC(50)>100 MUg/mL).
      These observations offer promise for a new drug treatment regimen to augment and
      complement the current chemotherapy of TB.

PMID- 22664189
TI  - Using recombinant DNA technology for the development of live-attenuated dengue
      vaccines.
AB  - Dramatic increases in dengue (DEN) incidence and disease severity have been
      reported, in great part due to the geographic expansion of Aedes aegypti and
      Aedes albopictus mosquitoes. One result is the expanded co-circulation of all
      dengue 1-4 serotype viruses (DENV) in urban areas worldwide, especially in South
      and South-East Asia, and South America. DEN disease severity ranges from
      asymptomatic infections to febrile dengue fevers (DF) to life-threatening dengue
      hemorrhagic fever (DHF) and dengue shock syndrome (DSS). There is an urgent need
      for a safe and effective tetravalent DEN vaccine. Several live attenuated,
      tetravalent DEN vaccine candidates have been generated by recombinant DNA
      technology; these candidates are capable of providing immunity to all four DENV
      serotypes. In this paper we review (a) recombinant live-attenuated DEN vaccine
      candidates in terms of deletion, antigen chimerization, and the introduction of
      adaptive mutations; (b) strategies for improving tetravalent vaccine attenuation;
      and (c) live-attenuated DENV vaccine development.

PMID- 22664190
TI  - Overexpression of NAD kinases improves the L-isoleucine biosynthesis in
      Corynebacterium glutamicum ssp. lactofermentum.
AB  - NADPH is the key cofactor in L-isoleucine (Ile) biosynthetic pathway. To increase
      the Ile biosynthesis in Corynebacterium glutamicum ssp. lactofermentum JHI3-156,
      NADPH supply needs to be enhanced. Here NAD kinase, the key enzyme for the de
      novo biosynthesis of NADP(+) and NADPH, were cloned and expressed in JHI3-156,
      and their influences on Ile production were analysed. Meanwhile, enzyme
      properties of NAD kinase from JHI3-156 (CljPpnK) were compared with that from C.
      glutamicum ssp. lactofermentum ATCC 13869 (ClPpnK). Four variations existed
      between CljPpnK and ClPpnK. Both PpnKs were poly(P)/ATP-dependent NAD kinases
      that used ATP as the preferred phosphoryl donor and NAD(+) as the preferred
      acceptor. CljPpnK exhibited a higher activity and stability than ClPpnK and less
      sensitivity towards the effectors NADPH, NADP(+), and NADH, partly due to the
      variations between them. The S57P variation decreased their activity. Expression
      of CljppnK and ClppnK in JHI3-156 increased the ATP-NAD(+) kinase activity by 69-
      and 47-fold, respectively, the intracellular NADP(+) concentration by 36% and
      101%, respectively, the NADPH concentration by 95% and 42%, respectively, and Ile
      production by 37% and 24%, respectively. These results suggest that
      overexpressing NAD kinase is a useful metabolic engineering strategy to improve
      NADPH supply and isoleucine biosynthesis.

PMID- 22664191
TI  - Enzyme activity assay for horseradish peroxidase encapsulated in peptide
      nanotubes.
AB  - Encapsulation of horseradish peroxidase (HRP) inside a peptide nanotube (PNT) was
      demonstrated and its activity was measured. Enzyme assay verified that 0.16 MUg
      of the enzymes were encapsulated in 1mg of PNTs. The encapsulation was also
      verified with TEM, UV-vis spectroscopy, and FTIR. The activity of the
      encapsulated HRP was examined for thermal stability, long-term storage stability,
      and resistance to a denaturant. They showed good storage stability, retaining its
      activity up to 90%, while the free HRP lost 50% of its activity over the course
      of 18 days. At 55  degrees C, the encapsulated HRP activity remained 20% higher
      than that of the free HRP. With the denaturant, guanidinium hydrochloride
      (GdmHCl), the encapsulated HRP activity was maintained around 10% higher than the
      free HRP. This result proves that the encapsulation of HRP inside the PNT may be
      an effective way to keep the enzyme activity stable in various environments.

PMID- 22664192
TI  - Enzymatic characterization of Bacillus licheniformis gamma-glutamyltranspeptidase
      fused with N-terminally truncated forms of Bacillus sp. TS-23 alpha-amylase.
AB  - Bacillus licheniformis gamma-glutamyltranspeptidase (BlGGT) was fused at its C
      terminal end with N-terminally truncated forms of Bacillus sp. TS-23 alpha
      amylase. BlGGT and six fusion enzymes, BlGGT/SBD, BlGGT/AMYDeltaN476,
      BlGGT/AMYDeltaN443, BlGGT/AMYDeltaN376, BlGGT/AMYDeltaN195, and
      BlGGT/AMYDeltaN34, were over-expressed in Escherichia coli M15 cells and purified
      to apparent homogeneity by metal-affinity chromatography. The fusion
      constructions had no significant effect on the autocatalytic processing of BlGGT.
      Progressive decrease in the GGT activity of fusion proteins was associated with
      an increasing level of truncation, and only BlGGT/AMYDeltaN34 reserved the
      amylolytic activity. The protein fusions did not alter the optimal temperature
      and pH of BlGGT. However, as compared with the parental BlGGT, a significant
      change in circular dichorism and fluorescence spectra was observed in the fusion
      enzymes. Thermal unfolding of BlGGT, BlGGT/AMYDeltaN476, BlGGT/AMYDeltaN443, and
      BlGGT/AMYDeltaN376 followed the two-state unfolding process with a transition
      point (T(m)) of 61.3-63.1  degrees C, whereas BlGGT/AMYDeltaN195 and
      BlGGT/AMYDeltaN34 displayed two temperature transitions at 40.6 and 46.7  degrees
      C as well as at 62.8 and 62.9  degrees C, respectively. All of the fusion enzymes
      exhibited the raw-starch-binding ability, and the adsorbed proteins could be
      eluted from the adsorbent by 50mM Tris-HCl (pH 9.0) containing 2% soluble starch.

PMID- 22664193
TI  - An analysis of the concentration change of intermediate metabolites by gene
      manipulation in fatty acid biosynthesis.
AB  - In this report, concentration of malonic acid and acetic acid produced in
      Escherichia coli were investigated by the expression of acetyl-CoA carboxylase
      genes (accs) and a malonyl-CoA:ACP transacylase gene (fabD). Both malonyl-CoA and
      acetyl-CoA are essential intermediate metabolites in the fatty acid biosynthetic
      pathway, and are reversibly transformed to malonic acid and acetic acid,
      respectively in the cell. Acetyl-CoA is converted to malonic-CoA by acetyl-CoA
      carboxylases (Accs), which are composed of 3 different subunits (AccA, AccB, and
      AccC), and the resulting malonyl-CoA is then converted to malonyl-[acp] by
      malonyl-CoA:ACP transacylase (FabD). In this study, these genes were separately
      cloned, and the influences of overexpression of 4 different genes on the
      concentration of malonic acid and acetic acid were analyzed. Compared with the
      wild type E. coli, a recombinant strain containing 3 acc genes together showed a
      41.03% enhanced malonic acid production, and a 4.29-fold increased ratio of
      malonic acid to acetic acid.

PMID- 22664194
TI  - High-yield secretion of multiple client proteins in Aspergillus.
AB  - Production of pure and high-yield client proteins is an important technology that
      addresses the need for industrial applications of enzymes as well as scientific
      experiments in protein chemistry and crystallization. Fungi are utilized in
      industrial protein production because of their ability to secrete large
      quantities of proteins. In this study, we engineered a high-expression-secretion
      vector, pEXPYR that directs proteins towards the extracellular medium in two
      Aspergillii host strains, examine the effect of maltose-induced over-expression
      and protein secretion as well as time and pH-dependent protein stability in the
      medium. We describe five client proteins representing a core set of hemicellulose
      degrading enzymes that accumulated up to 50-100 mg/L of protein. Using a
      recyclable genetic marker that allows serial insertion of multiple genes,
      simultaneous hyper-secretion of three client proteins in a single host strain was
      accomplished.

PMID- 22664195
TI  - Two plate-based colorimetric assays for screening alpha-amino acid ester
      hydrolase with high synthesis/hydrolysis ratio.
AB  - alpha-Amino acid ester hydrolases (AEHs) are enzymes of interest to the semi
      synthesis of beta-lactam antibiotics with alpha-amino, such as cephalexin and
      cefaclor. An undesired side reaction, the hydrolysis of alpha-amino acid ester,
      had hindered applications in antibiotics synthesis. Although the enzymes' S/H
      ratio can be increased by protein engineering, such approaches require a suitable
      screening assay. Such a screening assay has not yet been described for AEHs. In
      this paper, we report a 96-well plate format screening procedure for AEHs based
      on two spectrophotometric assays. To reduce the hydrolysis reaction while
      maintaining synthesis activity, and to evaluate the effectiveness of the
      screening strategy, we introduced random mutations in part of the aeh gene from
      Xanthomonas rubrillineans by error-prone PCR. By a parallel plate-based screening
      strategy, three mutants with improved S/H ratio, R87L, T132N and N219I, were
      obtained.

PMID- 22664196
TI  - Laccase-poly(lactic-co-glycolic acid) (PLGA) nanofiber: highly stable, reusable,
      and efficacious for the transformation of diclofenac.
AB  - Nanobiocatalysis has received growing attention for use in commercial
      applications. We investigated the efficiency, stability, and reusability of
      laccase-poly(lactic-co-glycolic acid) (PLGA) nanofiber for diclofenac
      transformation. NH stretching vibrations (3400-3500 cm(-1) and 1560 cm(-1)) in FT
      IR spectra confirmed immobilization of laccase on PLGA nanofibers. The relative
      activity of immobilized laccase was 82% that of free laccase. Immobilized laccase
      had better storage, pH, and thermal stability than free laccase. The immobilized
      laccase produced complete diclofenac transformation in three reuse cycles, which
      was extended to 6 cycles in the presence of syringaldehyde. Results suggest that
      laccase-PLGA nanofiber may be useful for removing diclofenac from aqueous sources
      and has potential for other commercial applications.

PMID- 22664197
TI  - Construction and co-expression of plasmid encoding xylitol dehydrogenase and a
      cofactor regeneration enzyme for the production of xylitol from D-arabitol.
AB  - The biotransformation of D-arabitol into xylitol was investigated with focus on
      the conversion of D-xylulose into xylitol. This critical conversion was
      accomplished using Escherichia coli to co-express a xylitol dehydrogenase gene
      from Gluconobacter oxydans and a cofactor regeneration enzyme gene which was a
      glucose dehydrogenase gene from Bacillus subtilis for system 1 and an alcohol
      dehydrogenase gene from G. oxydans for system 2. Both systems efficiently
      converted D-xylulose into xylitol without the addition of expensive NADH.
      Approximately 26.91 g/L xylitol was obtained from around 30 g/L D-xylulose within
      system 1 (E. coli Rosetta/Duet-xdh-gdh), with a 92% conversion yield, somewhat
      higher than that of system 2 (E. coli Rosetta/Duet-xdh-adh, 24.9 g/L, 85.2%). The
      xylitol yields for both systems were more than 3-fold higher compared to that of
      the G. oxydans NH-10 cells (7.32 g/L). The total turnover number (TTN), defined
      as the number of moles of xylitol formed per mole of NAD(+), was 32,100 for
      system 1 and 17,600 for system 2. Compared with that of G. oxydans NH-10, the TTN
      increased by 21-fold for system 1 and 11-fold for system 2, hence, the co
      expression systems greatly enhanced the NADH supply for the conversion,
      benefiting the practical synthesis of xylitol.

PMID- 22664198
TI  - Special issue: the molecular and cellular mechanisms of amyloidosis.

PMID- 22664199
TI  - Muscles and tendons of a nucleosome remodeling machine.

PMID- 22664200
TI  - New perspectives in udder health management.

PMID- 22664201
TI  - Antimicrobial resistance of mastitis pathogens.
AB  - Antibiotics are used extensively in the dairy industry to combat disease and to
      improve animal performance. Antibiotics such as penicillin, cephalosporin,
      streptomycin, and tetracycline are used for the treatment and prevention of
      diseases affecting dairy cows caused by a variety of gram-positive and gram
      negative bacteria. Antibiotics are often administrated routinely to entire herds
      to prevent mastitis during the dry period. An increase in the incidence of
      disease in a herd generally results in increased use of antimicrobials, which in
      turn increases the potential for antibiotic residues in milk and the potential
      for increased bacterial resistance to antimicrobials. Continued use of
      antibiotics in the treatment and prevention of diseases of dairy cows will
      continue to be scrutinized. It is clear that strategies employing the prudent use
      of antimicrobials are needed. This clearly illustrates the importance of
      effective herd disease prevention and control programs. Based on studies
      published to date, scientific evidence does not support widespread, emerging
      resistance among mastitis pathogens to antibacterial drugs even though many of
      these antibiotics have been used in the dairy industry for treatment and
      prevention of disease for several decades. However, it is clear that use of
      antibiotics in dairy cows can contribute to increased antimicrobial resistance.
      While antimicrobial resistance does occur, we are of the opinion that the
      advantages of using antibiotics for the treatment of mastitis far outweigh the
      disadvantages. The clinical consequences of antimicrobial resistance of dairy
      pathogens affecting humans appear small. Antimicrobial resistance among dairy
      pathogens, particularly those found in milk, is likely not a human health concern
      as long as the milk is pasteurized. However, there are an increasing number of
      people who choose to consume raw milk. Transmission of an antimicrobial-resistant
      mastitis pathogen and/or foodborne pathogen to humans could occur if contaminated
      unpasteurized milk is consumed, which is another important reason why people
      should not consume raw milk. Likewise, resistant bacteria contaminating meat from
      dairy cows should not be a significant human health concern if the meat is cooked
      properly. Prudent use of antibiotics in the dairy industry is important,
      worthwhile, and necessary. Use of antibiotics at times when animals are
      susceptible to new infection such as the dry period is a sound management
      decision and a prudent use of antibiotics on the farm. Strategies involving
      prudent use of antibiotics for treatment encompass identification of the pathogen
      causing the infection, determining the susceptibility/resistance of the pathogen
      to assess the most appropriate antibiotic to use for treatment, and a sufficient
      treatment duration to ensure effective concentrations of the antibiotic to
      eliminate the pathogen. As the debate on the use of antibiotics in animal
      agriculture continues, we need to consider the consequences of, "What would
      happen if antibiotics are banned for use in the dairy industry and in other food
      producing animals?" The implications of this question are far reaching and
      include such aspects as animal welfare, health, and well-being and impacts on
      food quantity, quality, and food costs. This question should be an important
      aspect in this ongoing and controversial debate!

PMID- 22664202
TI  - The role of diagnostic microbiology in mastitis control programs.
AB  - There are a number of important issues for the dairy practitioner to consider in
      designing the most appropriate mastitis microbiological service for his or her
      clients. These include the decision to use enhancement tools or selective agars
      to optimize sensitivity and specificity. The service should include a monthly BTC
      service that monitors for the important contagious mastitis organisms: S aureus,
      S agalactia, and Mycoplasma. At the cow level, a zero tolerance program to
      protect healthy cows from exposure to contagious mastitis will require a routine
      culture service to monitor for these pathogens in new herd additions, clinical
      cases, and all fresh cows and heifers. A wide variety of additional benefits for
      maintaining good udder health and the production of quality milk can come from a
      more comprehensive diagnostic service that looks at both individual cow and bulk
      tank milk. Finally, more practitioners can help their clients economically by
      implementation of an on-farm TNT culture service and significantly reducing the
      use of intramammary therapy.

PMID- 22664203
TI  - Update on control of Staphylococcus aureus and Streptococcus agalactiae for
      management of mastitis.
AB  - The primary method of spread for S agalactiae and S aureus is from cow to cow, so
      prevention focuses on within and between herd biosecurity to reduce or eliminate
      the reservoir of infection. S agalactiae is an obligate pathogen of the mammary
      gland, whereas S aureus is more widespread on other cow body sites and in the
      environment. Both organisms cause persistent infections, with S agalactiae
      typically causing higher SCC and bacteria counts in milk. Conventional methods of
      detection through culture perform well at the cow level. In bulk tanks, augmented
      procedures should be considered. PCR methods show promise of high sensitivity and
      specificity, at both the cow and bulk tank level. In developed dairy industries,
      prevalence of infection has decreased dramatically over the past 30 years for S
      agalactiae. For S aureus, the herd level of infection remains very high, although
      with rigorous, consistent application of control measures, within-herd prevalence
      has decreased. Because the milking time is the primary period for new IMI, it is
      the focal point of most prevention activities. Premilking and postmilking teat
      disinfection and proper stimulation and milk-out with adequately functioning
      equipment are key factors. There is growing evidence that the use of milking
      gloves is an integral part of contagious mastitis control and the production of
      high-quality milk. Treatment success is dramatically different between the 2
      pathogens. For S agalactiae, eradication can be completed rapidly through a
      culture and treatment program with minimal culling. For S aureus, treatment
      success, particularly during lactation, is often disappointing and depends on
      cow, pathogen, and treatment factors. These factors should be reviewed prior to
      initiating any treatment to determine the potential for cure. Blanket dry cow
      therapy and strategic culling are important control procedures for contagious
      mastitis pathogens. Maintaining a closed herd or, at minimum, adhering to clearly
      defined biosecurity protocols is critical to reduce risk of reintroduction of S
      agalactiae or the addition of new, potentially more virulent strains of S aureus
      to endemic herds.

PMID- 22664204
TI  - Managing environmental mastitis.
AB  - Many of the practices and principals of management for reducing the exposure of
      dairy cows to environmental mastitis pathogens were introduced a quarter of a
      century ago22-25 and have been the subject of numerous reviews.1,3,21 The common
      theme for reducing mastitis pathogens in the cows' environment is reducing
      moisture and organic contamination.1 Frequent manure removal, avoiding
      overstocking of cows, taking precautions to eliminate stagnant water around cows,
      and providing clean, dry inorganic bedding for cows to lay on are important
      management considerations. These factors of environmental hygiene transcend stall
      barns, manure pack barns, open corrals, and pasture systems. The emphasis of
      control should center on protecting periparturient animals during wet, hot
      periods of the year when mastitis pathogen growth in the environment is greatest.
      As the dairy industry in North America changes and progresses to adapt to
      economic, social, and environmental demands, the old adage of keeping cows cool,
      dry, and comfortable remains paramount in managing environmental mastitis.

PMID- 22664205
TI  - Mycoplasma mastitis: causes, transmission, and control.
AB  - Mycoplasma mastitis is an emerging mastitis pathogen. Herd prevalence has
      increased over the past decade, and this increase parallels the increase in
      average dairy herd size. It has been documented that the importation of cattle
      into a herd can result in new cases of Mycoplasma disease in general and
      Mycoplasma mastitis specifically. Thus, expanding herds are likely to have a
      greater incidence of this disease. Transmission of the agent can result from
      either contact with diseased animals or with colonized or asymptomatically
      infected cattle. Initial transmission might occur via nose-to-nose contact and
      result in an outbreak of Mycoplasma mastitis, or it might occur during the
      milking time. This would suggest that new, incoming animals should be quarantined
      before being comingled with original herd animals. Quarantining does not seem to
      be a biosecurity strategy often practiced in control of Mycoplasma mastitis and
      may not be warranted in herds with excellent milking time hygiene practices. The
      ability to monitor for the incipient stages of an outbreak, often done through
      bulk tank milk culturing, is recommended.

PMID- 22664206
TI  - The "other" gram-negative bacteria in mastitis: Klebsiella, serratia, and more.
AB  - Mastitis caused by gram-negative infections is of increasing importance on modern
      and well-managed dairy farms. Without a doubt, E coli tends to be the most
      important cause of these gram-negative infections when the data are tallied
      across farms.1 However, more precise investigation of individual farms often
      reveals a farm-specific infection pattern where a single gram-negative bacterial
      species predominates. Several farms with a predominance of "other" gram-negative
      IMIs may be observed. We have shown the presence of outbreaks on individual dairy
      farms with K pneumoniae, S marcescens, and Enterobacter cloacae. On farms with a
      predominance of these "other" gram-negative infections, a detailed epidemiologic
      investigation may reveal the source of these infections. It is quite surprising
      to identify the difference in host immune response pattern and the associated
      clinical and subclinical presentations of IMIs due to the different gram-negative
      organisms. Experimental and field observations would suggest that among the gram
      negative bacterial causes of mastitis, Klebsiella spp are causing the most severe
      cases, closely followed by E coli and then much less clinical severity is
      observed in Serratia spp and Enterobacter spp cases. The precise mechanisms that
      would explain the difference in clinical severity are not known, but the most
      likely explanation appears to be the structure of the lipid A fraction of the LPS
      of the bacterial species. Important differences in the lipid A fraction of LPS
      between and within bacterial species are observed. The prevention of IMIs with
      gram-negative bacteria has components that are generic across species and
      components that are species specific. Generic prevention may be obtained by
      improving hygiene and reducing exposure of teat ends to environmental
      contamination. Also the use of a J5 bacterin is expected to provide some
      reduction in severity of gram-negative IMIs across bacterial species. Specific
      prevention programs will depend on the actual transmission behavior of the
      dominant species causing IMIs in the herd. Several clonal outbreaks of gram
      negative bacterial species have been described. In such situations, optimal
      milking procedures, segregation and culling of infected animals, and targeted
      treatment would be advisable. Even more specific are the prevention procedures
      associated with S marcescens outbreaks, where resistance against specific
      biocides will lead to transmission of infection through teat disinfectants.
      Removal of these biocides from the cow environment is than essential.
      Antimicrobial treatment of gram-negative bacteria has often considered to be of
      limited value and treatment should be more targeted toward cow survival and
      reduction of clinical symptoms. More recently, extended treatment with a third
      generation cephalosporin was reported to be efficacious in the treatment of E
      coli and Klebsiella spp but not of E cloacae. Further investigations in effective
      treatment protocols for gram-negative IMIs are warranted.

PMID- 22664207
TI  - Vaccination strategies for mastitis.
AB  - Presently, the most successful use of vaccination strategies as part of a dairy
      herd mastitis control program involves GNCABs, of which the J-5 bacterins are
      best understood. Immunization protocols employing this technology should be
      adapted to individual herd needs. Ironically, the success of these bacterins may
      rely, in part, on the systemic pathogensis of severe coliform mastitis. Because
      immune function is impaired in the mammary gland of a lactating dairy cow, and
      the difficulty in maintaining effective concentrations of antibodies in milk
      following vaccination, vaccines developed against pathogens that cause more
      chronic IMI, while promising, have significant obstacles to overcome.

PMID- 22664208
TI  - Treatment of clinical mastitis.
AB  - In summary, culture-based therapy and severity levels are key to management of
      clinical mastitis. Antibiotic therapy should be strongly considered for gram
      positive clinical mastitis. Antibiotic therapy is not necessary for mild-to
      moderate gram-negative clinical mastitis. Antibiotic therapy is warranted for
      practically all severe clinical mastitis as well as fluids and anti-inflammatory
      drugs. Clinical mastitis cases due to yeast and fungal pathogens or no growth
      isolates do not warrant antibiotic therapy.

PMID- 22664209
TI  - Assessment and management of pain in dairy cows with clinical mastitis.
AB  - It is clear that clinical mastitis has severe detrimental effects on the animal
      and negative economic impacts for dairy producers. However, pain associated with
      clinical mastitis, generally, is not measured and not treated. Attention to
      behavioral and physiologic indicators should be used to monitor animal health.
      New technologies may allow dairy producers to identify clinical mastitis in its
      very early stages, or even before clinical changes occur. Furthermore, automated
      measures of activity, such as step counts and lying time, show promise as
      predictors of clinical problems. These new technologies, in addition to other
      automated measures, have the potential for improving the screening methods for
      preclinical mastitis and accurately predicting the onset of a clinical mastitis
      event. With this opportunity for very early detection of infection, there is a
      potential for early intervention with NSAID therapy, which may allow for maximum
      efficacy from its use. Despite which specific NSAID is used, it is clear that the
      benefits on temperature, rumen function, SCC, milk production, behavior, and pain
      sensitivity in animals during mastitis indicate that this therapy has a role
      throughout the dairy industry. As the health and well-being of dairy cattle
      continue to be scrutinized by consumer groups, it is essential that the
      alleviation of any perceived pain or discomfort associated with clinical mastitis
      should be addressed.

PMID- 22664210
TI  - The role of the milking machine in mastitis control.
AB  - Most NIs are caused by factors other than the milking machine. Direct and
      indirect milking machine effects may account for up to 20% of NIs in some herds
      and, probably, not much more than about 10% in an "average" herd these days
      provided that machine settings are right. Thus, proper maintenance and operation
      of any milking system is a key aspect of successful milking.

PMID- 22664211
TI  - Stray voltage and milk quality: a review.
AB  - If animal contact voltage reaches sufficient levels, animals coming into contact
      with grounded devices may receive a mild electric shock that can cause a
      behavioral response. At voltage levels that are just perceptible to the animal,
      behaviors indicative of perception (eg, flinches) may result with little change
      in normal routines. At higher exposure levels, avoidance behaviors may result.
      The direct effect of animal contact with electrical current can range from: *
      Mild behavioral reactions indicative of sensation, to * Involuntary muscle
      contraction, or twitching, to * Intense behavioral responses indicative of pain.
      The indirect effects of these behaviors can vary considerably depending on the
      specifics of the contact location, level of current flow, body pathway, frequency
      of occurrence, and many other factors related to the daily activities of animals.
      There are several common situations of concern in animal environments: * Animals
      avoiding certain exposure locations, which may result in: X Reduced water intake
      if exposure is required for animals to access watering devices, X Reduced feed
      intake if exposure is required for animals to accesses feeding devices or
      locations. * Difficulty of moving or handling animals in areas of voltage/current
      exposure* The physiologic implications of the release of stress hormones produced
      by contact with painful stimuli. The severity of response will depend on the
      amount of electrical current (measured in milliamps) flowing through the animal's
      body, the pathway it takes through the body, and the sensitivity of the
      individual animal. The results of the combined current dose-response experiments,
      voltage exposure response experiments, and measurements of body and contact
      resistances is consistent with the lowest (worst case) cow + contact resistance
      as low as 500 as estimated by Lefcourt that may occur in some unusual situations
      on farms (firm application of the muzzle to a wet metallic watering device and
      hoof contact on a clean, wet, contoured metallic plate on the floor). These
      studies on responses of dairy cows to electrical exposure agree well with each
      other and with predictions from neuroelectric theory and practice. There is a
      high degree of repeatability across studies in which exposures and responses have
      been appropriately quantified. For confirmation, a potential of 2 to 4 V (60 Hz,
      rms) must be measured between 2 points that an animal might contact (or animal
      contact measurement), and some animals should exhibit signs of avoidance
      behavior. The animal contact voltage measurement with an appropriate shunt
      resistor value provides the only reliable indication of exposure levels. Voltage
      readings at cow contact points should be made with a 500- or 1000- resistor
      across the 2 measuring leads to the cow contact points in addition to open
      circuit measurements. The only studies that have documented adverse effects of
      voltage and current on cows had both sufficient current applied to cause aversion
      and forced exposures (ie, animals could not eat or drink without being exposed to
      voltage and current) and all of the indirect responses (reduced water or intake
      and milk production) were behaviorally mediated. It is typical for voltage levels
      to vary considerably at different locations on a farm. Decreased water and/or
      feed intake or undesired behaviors result only if current levels are sufficient
      to produce aversion at locations that are critical to daily animal activity, such
      as feeders, waterers, and milking areas. If an aversive current occurs only a few
      times per day, it is not likely to have an adverse effect on cow behavior. The
      more often an aversive voltage occurs in areas critical to cows' normal feeding,
      drinking, or resting, the more likely it is to affect cows. A number of studies
      have been done to investigate potential detrimental physiologic responses that
      may result from animals' exposure to voltage and current. The literature review
      presented here summarizes 46 research trials on groups of cows exposed to know
      levels of voltage and/or current. Many of these were part of the same experiment
      but exposed cows at different levels of voltage or current. None of these trials
      or experiments (some using aggressive exposure of cows to mastitis organisms)
      showed a significant effect of voltage/current exposure on SCC or the incidence
      of mastitis. Many of these studies showed behavioral modification and some showed
      minor changes in milk yield, milk composition, or stress hormones (especially
      cortisol). These studies have shown that increased concentrations of the stress
      hormone cortisol do not occur at levels below behavioral response levels and only
      become apparent in some, but not all, cows at substantially higher
      voltage/current exposures than the threshold required for behavioral
      modification. This body of research indicates that while exposure to stray
      voltage at levels of 2 V to 4 V may be a mild stressor to dairy cows, it does not
      contribute to increased SCC or incidence of mastitis or reduced milk yield.

PMID- 22664212
TI  - Using mastitis records and somatic cell count data.
AB  - Developing a records plan useful for managing the complex relationships between
      environment, personal application of SOP, and protocols that integrates clinical
      and subclinical udder requires planning the data entry and data reports that
      interpret the herd without abandoning the individual cow. Then use the data
      regularly.

PMID- 22664213
TI  - The role of communication in improving udder health.
AB  - Our findings provide insight into Dutch dairy farmers' behavior and mindset
      toward mastitis management, and into the way these can be affected by
      communication strategies. They may differ from those of North American dairy
      farmers, but probably many findings are comparable. Elements of farmer mindset
      are important determining factors in mastitis control, including the perceived
      threat (ie, "Do I have a problem?") and the perceived efficacy of mastitis
      management measures (ie, "Can I solve the problem easily?"). These issues need to
      be addressed in communication strategies. Veterinarians can be important
      intermediaries in communication about udder health, provided that they are aware
      of their role as proactive advisor and apply the accompanying communication
      skills. To be effective, a mastitis control program should do more than
      distributing technical information about best management practices to dairy
      farmers. Prevention of complex diseases such as mastitis requires customized
      communication strategies as well as an integrated approach between various
      stakeholders and different scientific disciplines. Because farmers are part of,
      and are influenced by a wide institutional context, such programs need to be
      supported by a combination of several policy measures to change farm management
      in the long run.

PMID- 22664214
TI  - Mastitis in dairy cows.

PMID- 22664215
TI  - [Renal failure and hantavirus].

PMID- 22664216
TI  - [Chagas disease in Spain, 2012].

PMID- 22664217
TI  - [Electronic media used by medical students during theoretical classes: are they
      learning instruments or distractions sources?].

PMID- 22664218
TI  - Neuroglobin upregulation offers neuroprotection in traumatic brain injury.
AB  - OBJECTIVES: The aim of this study was to investigate rat neuroglobin (rNGB)
      expression level after traumatic brain injury (TBI) and further study its
      neuroprotective effects in TBI when it was overexpressed in adenoviral vector.
      METHODS: The Wistar rats (280-320  g) were divided into control, 12 and 36 hours
      after TBI groups (n = 3) and their TBI model was established. Subsequently, NGB
      expression level was examined by Western blot and immunohistochemical. Beyond
      that, adenoviral vectors pAdEasy-rNGB-GFP and pAdEasy-GFP  were constructed and
      transfected into the rat brain respectively (pAdEasy-GFP was control), and the
      neuroprotective effects were examined by immunohistochemical. RESULTS:
      Immunohistochemical and Western blot results demonstrated that NGB expression
      level was increased at 12  and 36 hours after TBI injury compare with control.
      Meanwhile, the pAdEasy-rNGB-GFP transfected rats suffered less necrosis and
      apoptosis compare to control. CONCLUSIONS: NGB was upregulated in TBI and
      overexpressed rNGB had a significant neuroprotection in TBI. However,  the
      mechanism remained unknown. This study suggested that rNGB overexpression may be
      a new strategy for treating of TBI.

PMID- 22664219
TI  - Posterior musculofascial reconstruction after radical prostatectomy: a systematic
      review of the literature.
AB  - CONTEXT: In 2001, Rocco et al. described a surgical technique whose aim was the
      reconstruction of the posterior musculofascial plate after radical prostatectomy
      (RP) to improve early return to urinary continence. Since then, many surgeons
      have applied this technique-either as it was described or with some modification
      to open, laparoscopic, and robot-assisted RP. OBJECTIVE: To review the outcomes
      reported in comparative studies analysing the influence of reconstruction of the
      posterior aspect of the rhabdosphincter after RP. The main outcome evaluated was
      urinary continence at 3-7 d, 30-45 d, 90 d, 180 d, and 1 yr after catheter
      removal. EVIDENCE ACQUISITION: A systematic review of the literature was
      performed in November 2011, searching the Medline, Embase, Scopus, and Web of
      Science databases. A "free-text" protocol using the terms posterior
      reconstruction of the rhabdosphincter, posterior rhabdosphincter, and early
      continence was applied. Studies published only as abstracts and reports from
      meetings were not included in this review. One thousand seven records were
      retrieved from the Medline database, 1541 from the Embase database, 1357 from the
      Scopus database, and 1041 from the Web of Science database. The authors reviewed
      the records to identify studies comparing cohorts of patients who underwent RP
      with or without restoration of the posterior aspect of the rhabdosphincter. Only
      papers evaluating use of this technique as the only technical modification among
      the groups were included. A cumulative analysis was conducted using Review
      Manager v.5.1 software (Cochrane Collaboration, Oxford, UK). EVIDENCE SYNTHESIS:
      Eleven studies were identified in the literature search, including two randomised
      controlled trials (RCTs), which were negative studies. The cumulative analysis of
      comparative studies showed that reconstruction of the posterior musculofascial
      plate improves early return of continence within the first 30 d after RP
      (p=0.004), while continence rates 90 d after surgery are not affected by use of
      the reconstruction technique. The statistical significance of the reconstruction
      seems to decrease when higher continence rates are reported. Use of posterior
      rhabdosphincter reconstruction does not seem to be related to positive surgical
      margin (PSM) rates or with complications like acute urinary retention (AUR) and
      bladder neck stricture (BNS). Some studies suggested lower anastomotic leakage
      rates with the posterior musculofascial plate reconstruction technique.
      CONCLUSIONS: The role of reconstruction of the posterior musculofascial plate in
      terms of earlier continence recovery is encouraging but still controversial.
      Methodological flaws and poor surgical standardisation seem to be the major
      causes. In two RCTs and one parallel (not randomised) group trial, posterior
      rhabdosphincter reconstruction offered no significant advantage for return of
      early continence after RP. No significant complications related to the posterior
      musculofascial plate reconstruction technique have been reported so far. A
      multicentre RCT is necessary to clarify the possible role of the technique in
      terms of earlier continence recovery.

PMID- 22664220
TI  - The INs and OUTs of pattern recognition receptors at the cell surface.
AB  - Pattern recognition receptors (PRRs) enable plants to sense non-self molecules
      displayed by microbes to mount proper defense responses or establish symbiosis.
      In recent years the importance of PRR subcellular trafficking to plant immunity
      has become apparent. PRRs traffic through the endoplasmatic reticulum (ER) and
      the Golgi apparatus to the plasma membrane, where they recognize their cognate
      ligands. At the plasma membrane, PRRs can be recycled or internalized via
      endocytic pathways. By using genetic and biochemical tools in combination with
      bioimaging, the trafficking pathways and their role in PRR perception of
      microbial molecules are now being revealed.

PMID- 22664221
TI  - Occurrence of hemotrophic mycoplasmas in horses with correlation to hematological
      findings.
AB  - Hemotrophic mycoplasmas (HM) are small, cell wall-less bacteria and infections
      are known for a wide range of animals. One possible indication of equine HM
      infection was given in 1978, when a 'haemobartonellosis' outbreak was diagnosed
      in Nigerian horses by microscopy. However the first molecular proof of HM in
      horses was not reported until 2010, when a fragment of about 900 bp of the 16S
      rRNA of the equine HM was obtained. This sequence was used for the development of
      a SYBR green I real-time PCR assay specific for equine HM. The lower detection
      limit of the PCR was ten 16S rDNA copy numbers per ml of blood. The newly
      designed assay was successfully applied for the detection and quantification of
      HM in horses in Germany. A high sample prevalence of 26.5% (95% CI: 18.8-35.5%)
      was found (31 out of 117 horses). The mean bacterial load was 1.10*10(6) 16S rDNA
      copy number/ml blood (range: minimum 1.05*10(3), maximum 1.27*10(7)). Equine HM
      were also detected by microscopy (Giemsa and acridine orange stained blood
      smears), but results do not correlate very well with PCR results, as microscopy
      proved rather unspecific and not sensitive. In horses younger than one year, a
      significant correlation between PCR positive status and anemia was found. No
      correlation was found in PCR-positive animals older than one year. Therefore we
      assume that HM infection has a higher clinical relevance in young animals.

PMID- 22664222
TI  - Hospitalized children with pneumonia in Uruguay: pre and post introduction of 7
      and 13-valent pneumococcal conjugated vaccines into the National Immunization
      Program.
AB  - INTRODUCTION: Streptococcus pneumoniae pneumonia burden in children was poorly
      defined in Uruguay. A three-year population-based surveillance demonstrated the
      impact of the pneumonia in hospitalized children of less than five years of age.
      To control these diseases in March 2008, Uruguayan health authorities decided to
      incorporate PCV7 to the National Immunization Program administered at 2, 4 and 12
      months of age (2+1 schedule). OBJECTIVE: To compare the incidence of consolidated
      pneumonia hospitalization in children less than five years of age before and
      after pneumococcal conjugate vaccine implementation. METHODS: Same methodology of
      the prevaccination study was employed. The surveillance was carried out at the
      same four hospitals covering a population of 229,128 inhabitants (2004 Census) of
      whom 10.2% were under five years of age. Clinical data, vaccination status and
      digitization of their chest X-rays were recorded. A pediatric radiologist blinded
      to the clinical diagnosis interpreted the digital images according WHO
      definitions. Bacterial etiology was investigated in blood and/or in pleural
      fluid. RESULTS: Between January 1st 2009 and June 30th 2011 patients were
      enrolled. Out of 23,445 children<5 years of age, 1224 were hospitalized with
      pneumonia (430 consolidated pneumonias and 794 non consolidated pneumonias).
      Pleural effusion was recorded in 89 patients. In 48 consolidated pneumonias S.
      pneumoniae etiology was recognized. Post vaccination incidence rate of
      consolidated pneumonia in patients aged 12-23 months showed a significant
      reduction (44.9%) if we compare it with the incidence of pneumonia
      hospitalization in the previous study. In March 2010, PCV13 replaced PCV7.
      Compliance of PCV7/13 globally was 92% but the vaccination status varied among
      the surveyed patients because two catch-ups were carried out in addition to the
      routine cohort vaccination. From 2009 1st semester to 2011 1st semester incidence
      rates decline reached 59%. CONCLUSION: To date, the ongoing surveillance
      documented a significant decline on incidence of hospitalizations for
      consolidated pneumonia in children younger than 24 months of age, confirming the
      success of the 2+1 vaccination schedule.

PMID- 22664223
TI  - Human papillomavirus vaccination and sexual behaviour: cross-sectional and
      longitudinal surveys conducted in England.
AB  - OBJECTIVE: To examine whether HPV vaccination influences sexual behaviour in
      adolescent girls, either by giving them a 'green light' to have sex, or because
      perceived protection afforded by the vaccine permits compensatory risky sexual
      behaviour. DESIGN: Cross-sectional and longitudinal surveys. SETTING: Seven
      English schools. MAIN OUTCOME MEASURES: Self-reported sexual behaviour.
      PARTICIPANTS: The cross-sectional survey included 1053 girls (mean age 17.1
      years) who had (n=433 recruited in March 2010) or had not (n=620 recruited in
      March 2009) been offered the HPV vaccine. The longitudinal survey included 407
      girls (mean age 17.5 years) who had been offered HPV vaccination and had either
      received at least one dose (n=148) or had not received any doses (n=259).
      RESULTS: In the cross-sectional survey, the group of girls who had been offered
      the HPV vaccine were no more likely to be sexually active than the group of girls
      who had not been offered the HPV vaccine. In the longitudinal survey, the
      vaccinated group were no more likely to have changed their condom use or
      increased their total number of sexual partners than the unvaccinated group.
      CONCLUSIONS: Neither being offered the HPV vaccine nor receiving it affected
      sexual behaviour.

PMID- 22664224
TI  - Febrile events including convulsions following the administration of four brands
      of 2010 and 2011 inactivated seasonal influenza vaccine in NZ infants and
      children: the importance of routine active safety surveillance.
AB  - OBJECTIVE: To evaluate and compare rates of febrile events, including febrile
      convulsion, following immunisation with four brands of inactivated 2010 and 2011
      influenza vaccine in NZ infants and children. DESIGN: Retrospective telephone
      surveys of parents of infants and children who received at least one dose of the
      vaccines of interest. SETTING: 184 NZ General Practices who received the vaccines
      of interest. PARTICIPANTS: Recipients of 4088 doses of trivalent inactivated
      vaccines Fluvax((r)), Vaxigrip((r)), Influvac((r)) and Fluarix((r)) and/or
      monovalent Celvapan. Vaccinees were identified via the electronic Practice
      Management System and contacted consecutively. MAIN OUTCOME MEASURES: Primary
      outcome was febrile convulsive seizure. Secondary outcomes were presence of fever
      plus other organ system specific symptoms. RESULTS: The parental response rate
      was 99%. Of 4088 doses given, 865 were Fluvax((r)), 2571 Vaxigrip((r)), 204
      Influvac((r)), 438 Fluarix((r)) and 10 Celvapan. Three febrile convulsions
      followed Fluvax((r)), a rate of 35 per 10,000 doses. No convulsions occurred
      following any dose of the other vaccines. There were nine febrile events that
      included rigors, all following Fluvax((r)). Fever occurred significantly more
      frequently following administration of Fluvax((r)) compared with the other brands
      of vaccines (p<0.0001) and Fluvax recipients were more likely to seek medical
      attention. Influvac((r)) also had higher rates of febrile reactions (OR 0.54,
      0.36-0.81) than the other two brands Vaxigrip((r)) (OR 0.21, 0.16-0.27) and
      Fluarix((r)) (OR 0.10, 0.05-0.20). After multivariable analysis vaccine, European
      ethnicity and second dose of vaccine were significantly associated with reporting
      of fever within 24h of vaccination. CONCLUSIONS: Influenza vaccines have
      different rates of reactogenicity in children which varies between ethnic groups.
      High rates of febrile convulsions and reactions in children receiving Fluvax((r))
      and to a lesser extent the higher fever rates in those receiving Influvac((r))
      compared with the other two brands of influenza vaccines in this study suggests
      that reactogenicity profiles need to be considered prior to national policy
      advice each season. The risk-benefit profile in children might not be equally
      favourable for all licensed paediatric influenza vaccines. More attention needs
      to be given to comparative research for all trivalent seasonal vaccines, and with
      all strain changes.

PMID- 22664225
TI  - Spatial variation and contamination assessment of heavy metals in sediments in
      the Manwan Reservoir, Lancang River.
AB  - Due to the construction and operation of Manwan Dam on the Lancang River,
      sediments were likely to deposit in the impoundment. In this research, sediment
      samples were collected from 17 sites in the whole reservoir in 2011 to
      investigate the distribution and sources of heavy metals (Al, As, Cu, Fe, Cd, Cr,
      Mn, Pb and Zn), as well as to assess the heavy metal contamination status. The
      results obtained using Principal Component Analysis (PCA) showed that the sources
      of heavy metals were mainly divided into two groups, natural factors and
      anthropogenic input. The anthropogenic inputs mainly came from industrial
      activities of the tributary rivers such as heavy metal mining and smelting, and
      agricultural practices such as fertilising and pesticide consumption. The
      sediment quality was assessed according to the sediment guidelines and the
      enrichment factor (EF). Concentrations of As, Cd, Cr, Cu, Pb and Zn in sediments
      at some of the sites exceeded either the Threshold Effects Level (TEL) of US
      National Oceanic and Atmospheric Administration (NOAA) or Effects Range-Low (ERL)
      of the Canadian Sediment Quality guidelines. The high levels of these heavy
      metals could cause adverse effects. One-way analysis of variance for spatial
      analysis revealed that no significant differences were found for most heavy
      metals at the tail, centre and head of the reservoir except that Cr showed
      significant differences (P<0.01) at the reservoir centre and the head.
      Significant variations for some heavy metals were observed in the tributaries and
      in the mainstream. The comparative EF indices suggested that As, Cd, Pb, Zn and
      Mn were slightly enriched and Cr, Fe and Cu were not enriched but had different
      "high-low" orders at the tail, centre and head of the reservoir. We depicted
      distribution map of enrichment factors for all heavy metals and the potential
      ecological risk index (RI) was applied to produce the comprehensive risk
      distribution map.

PMID- 22664226
TI  - Biochemical responses and metals levels in Ruditapes decussatus after exposure to
      treated municipal effluents.
AB  - This study assessed the responses of biochemical biomarkers and metals levels in
      Ruditapes decussatus exposed to the increasing concentrations of treated
      municipal effluents (TME) discharged into the Tunisian coastal area. Clams were
      exposed to 0%, 1%, 3% and 10% for 7 and 14 day and the following biochemical
      responses were measured: (1) catalase activity and lipid peroxidation levels
      (TBARS) as oxidative stress biomarkers, (2) gluthathione S-transferase (GST)
      activity as a phase II conjugation enzyme; (3) cholinesterase activity (ChE) as
      biomarker of neurotoxicity, and (4) metallothioneins as a proteins highly induced
      by heavy metals. A significant uptake of Cu, Cd and Zn in digestive gland and
      serious biochemical alterations were observed. Thus, exposure of clams to
      croissant concentration of TME have the potential to increase the oxidative
      stress biomarkers (TBARS, CAT activity) and MT levels; and decrease ChE activity
      in both gills and digestive gland. Current experimental results suggest that CAT,
      GST, ChE activities and MT and TBARs levels in gills and digestive gland of clam
      R. decussatus are sensitive and suitable responses for assessing the effects of
      anthropogenic contaminants on the aquatic ecosystems, particularly effluent
      complex mixtures.

PMID- 22664227
TI  - Skimmin, a coumarin, suppresses the streptozotocin-induced diabetic nephropathy
      in wistar rats.
AB  - Skimmin, a major active ingredient from Hydrangea paniculata, was considered to
      have the possible preventive effect on the progression of diabetic nephropathy
      based on the traditional Chinese medicine. The present study aimed to assess this
      preventive activity in a rat model of diabetic nephropathy. Adult wistar rats
      were induced to develop diabetic nephropathy through injection of streptozotocin
      (60mg/kg). Animals were treated orally with saline, skimmin at 7.5, 15 and
      30mg/kg, and losartan (10mg/kg) daily for 17 weeks. At 7 and 17 weeks, blood and
      urine samples were collected for biochemical examination; at the end of 17 weeks,
      all the kidney tissues were collected for the histological examination. Enzyme
      linked immunosorbent assay (ELISA) and reverse transcription polymerase chain
      reaction (RT-PCR) were used to analyze the expression of transforming growth
      factor-beta 1(TGF-beta1) and its receptors in blood and kidney tissues
      respectively. Our results suggested that skimmin could decrease the Scr and
      glucose level in blood of diabetic rats significantly (P<0.01), and increase the
      creatinine clearance (P<0.01), similar changes were also observed in the losartan
      treated rats. In histological examination, skimmin-treated rats showed a
      significant decrease in glomcrulus segmented sclerosis and incidence of tubule
      vacuolar degeneration (P<0.01), similar but less significant beneficial effects
      were observed for losartan treatment. By ELISA, western blotting and RT-PCR, we
      found skimmin could down-regulate the TGF-beta1 and TGF-beta Receptor I
      expression both at protein and mRNA levels. This study suggests that the skimmin
      can suppress diabetic nephropathy in rats effectively, and may slow down the
      renal fibrosis by regulating TGF-beta1 signal pathway.

PMID- 22664228
TI  - Intra-operatively customized implant coating strategies for local and controlled
      drug delivery to bone.
AB  - Bone is one of the few tissues in the human body with high endogenous healing
      capacity. However, failure of the healing process presents a significant clinical
      challenge; it is a tremendous burden for the individual and has related health
      and economic consequences. To overcome such healing deficits, various concepts
      for a local drug delivery to bone have been developed during the last decades.
      However, in many cases these concepts do not meet the specific requirements of
      either surgeons who must use these strategies or individual patients who might
      benefit from them. We describe currently available methods for local drug
      delivery and their limitations in therapy. Various solutions for drug delivery to
      bone focusing on clinical applications and intra-operative constraints are
      discussed and drug delivery by implant coating is highlighted. Finally, a new set
      of design and performance requirements for intra-operatively customized implant
      coatings for controlled drug delivery is proposed. In the future, these
      requirements may improve approaches for local and intra-operative treatment of
      patients.

PMID- 22664229
TI  - Advancing risk assessment of engineered nanomaterials: application of
      computational approaches.
AB  - Nanotechnology that develops novel materials at size of 100nm or less has become
      one of the most promising areas of human endeavor. Because of their intrinsic
      properties, nanoparticles are commonly employed in electronics, photovoltaic,
      catalysis, environmental and space engineering, cosmetic industry and - finally -
      in medicine and pharmacy. In that sense, nanotechnology creates great
      opportunities for the progress of modern medicine. However, recent studies have
      shown evident toxicity of some nanoparticles to living organisms (toxicity), and
      their potentially negative impact on environmental ecosystems (ecotoxicity). Lack
      of available data and low adequacy of experimental protocols prevent
      comprehensive risk assessment. The purpose of this review is to present the
      current state of knowledge related to the risks of the engineered nanoparticles
      and to assess the potential of efficient expansion and development of new
      approaches, which are offered by application of theoretical and computational
      methods, applicable for evaluation of nanomaterials.

PMID- 22664230
TI  - Bone formation controlled by biologically relevant inorganic ions: role and
      controlled delivery from phosphate-based glasses.
AB  - The role of metal ions in the body and particularly in the formation, regulation
      and maintenance of bone is only just starting to be unravelled. The role of some
      ions, such as zinc, is more clearly understood due to its central importance in
      proteins. However, a whole spectrum of other ions is known to affect bone
      formation but the exact mechanism is unclear as the effects can be complex,
      multifactorial and also subtle. Furthermore, a significant number of studies
      utilise single doses in cell culture medium, whereas the continual, sustained
      release of an ion may initiate and mediate a completely different response. We
      have reviewed the role of the most significant ions that are known to play a role
      in bone formation, namely calcium, zinc, strontium, magnesium, boron, titanium
      and also phosphate anions as well as copper and its role in angiogenesis, an
      important process interlinked with osteogenesis. This review will also examine
      how delivery systems may offer an alternative way of providing sustained release
      of these ions which may effect and potentiate a more appropriate and rapid tissue
      response.

PMID- 22664232
TI  - Thyroid hormone within the normal range is associated with left ventricular mass
      in patients with hypertension.
AB  - Thyroid hormone amplifies hypertrophy of cardiac myocytes. The heart is
      influenced by the minimal changes of thyroid hormone levels. We hypothesized that
      thyroid hormone within the normal reference range may be associated with left
      ventricular (LV) mass in hypertensive subjects. We performed echocardiography to
      assess LV mass indexed by body surface area (LVMI), and measured thyroid
      stimulating hormone (TSH), free triiodo-thyronine (fT3), free thyroxine (fT4),
      and brain natriuretic peptide (BNP) in 318 hypertensive patients without known
      thyroidal diseases. Glomerular filtration rate (GFR) was estimated using the MDRD
      formula. Relationship between each thyroid hormone and LVMI in hypertensive
      patients with euthyroidism were investigated using a multiple linear regression
      model entering age, gender, height, weight, GFR, log BNP, systolic BP, the use of
      more than 2 different types of antihypertensive medications, and HbA1c as
      covariates. Thyroid hormone and TSH levels were within the normal range in 293
      patients. In these patients, fT3 (standard beta = 0.13) and fT4 (standard beta =
      0.11) positively, and TSH (standard beta = -0.15) inversely correlated with LVMI
      in the multiple linear regression model. Thyroid hormone may be associated with
      LV remodeling independent of renal and LV dysfunctions in hypertensive patients
      with euthyroidism.

PMID- 22664233
TI  - In situ lift-out dedicated techniques using FIB-SEM system for TEM specimen
      preparation.
AB  - The recent emergence of the focused ion-beam (FIB) microscope as a dedicated
      specimen preparation tool for transmission electron microscopy (TEM) has extended
      the reach of TEM to a wider variety of problems in materials science. This paper
      highlights three examples of using FIB-SEM lift-out techniques for preparing site
      specific and crystallographic orientation-specific thin-foil specimens. An in
      situ lift-out technique used to extract thin foils from across a local grain
      boundary in bulk Al alloy and from individual fine Al atomised powder particles
      (down to 20MUm in diameter) was performed with real-time secondary electron
      imaging within the chamber of a FIB-SEM system. In conjunction with electron
      backscatter diffraction (EBSD), the FIB is used for extracting TEM foil with a
      specific crystallographic orientation aligned normal to the broad plane of the
      foil. The above technique has been demonstrated using a dual-phase Ti-Si alloy
      for the exploration of orientation relationship between constituent phases.
      Furthermore, it is suggested that FIB is more applicable for preparing thin foils
      from hydrogen-sensitive metals (such as titanium alloys) than conventional
      thinning techniques, which tend to induce ambiguous artifacts in these foils.

PMID- 22664231
TI  - Nanoparticle mediated non-covalent drug delivery.
AB  - The use of nanoparticles (NPs) for enhanced drug delivery has been heavily
      explored during the last decade. Within the field, it is has become increasingly
      apparent that the physical properties of the particles themselves dictate their
      efficacy, and the relevant non-covalent chemistry at the NP interface also
      influences how drugs are immobilized and delivered. In this review, we reflect on
      the physical chemistry of NP mediated drug delivery (and more specifically, non
      covalent drug delivery) at the three main experimental stages of drug loading, NP
      drug conjugate transport, and the resulting cellular drug delivery. Through a
      critical evaluation of advances in drug delivery within the last decade, an
      outlook for biomedical applications of nanoscale transport vectors will be
      presented.

PMID- 22664234
TI  - [Bullous mastocytosis in infancy: a rare presentation].
AB  - Mastocytosis is a rare condition related to an abnormal proliferation of mast
      cells and their accumulation in tissues. Cutaneous mastocytosis is the most
      common form and mainly affects newborns and infants. The symptoms are caused by
      the release of mediators contained in mast cells, including histamine.
      Mastocytosis may be associated with a mutation in the gene encoding the c-kit
      receptor. Clinically, there are different dermatological findings, which combine
      acute cutaneous, digestive, or even hemodynamic manifestations in varying
      degrees. The diagnosis is confirmed by the histological study of a skin sample.
      We report here the case of a 4-month-old infant suffering from diffuse cutaneous
      bullous mastocytosis, a very rare variety of mastocytosis. This infant had an
      erosive and bullous manifestation of dermatosis, initially confused with
      impetigo. The proliferation of bullous lesions led to her hospitalization.
      Codeine intake for pain was responsible for a large and extensive bullous
      reaction associated with anaphylactic shock. This context of bullous spread
      occurring after taking codeine led to the suspicion of bullous diffuse cutaneous
      mastocytosis, a diagnosis that was confirmed histologically. This observation
      demonstrates the difficulty of mastocytosis diagnosis, mostly due to its rarity,
      especially in its diffuse bullous forms. The rapid deterioration of this patient,
      after the codeine prescription, emphasizes the importance of the eviction of
      histamine-releaser compounds in the management of this disease.

PMID- 22664235
TI  - Understanding the molecular mechanism of sequence dependent tenofovir removal by
      HIV-1 reverse transcriptase: differences in primer binding site versus polypurine
      tract.
AB  - Tenofovir (TFV) is a nucleotide reverse transcriptase inhibitor (NtRTI) that is
      often administered as first-line therapy against human immunodeficiency virus
      type-1 (HIV-1) infection and acts as a chain terminator when incorporated into
      viral DNA. However, HIV-1 reverse transcriptase (RT) excises TFV in the presence
      of either ATP or pyrophosphate, which is an important drug resistance mechanism
      that would interfere with the effective treatment. Previous studies have shown
      conflicting results on excision efficiencies for TFV-terminated primer-templates
      derived from either primer binding site (PBS) or polypurine tract (PPT)
      sequences. To provide mechanistic insight into the variation in TFV removal from
      both sequences that are vital for the HIV-1 life cycle, we compared the
      efficiencies of removal reaction in response to sequence dependence via utilizing
      blocked PBS and PPT primer-templates. We found an enhanced TFV excision with PPT
      sequence over PBS sequence through ATP-mediated removal and a subsequent
      incorporation of ATP into the unblocked primers. Furthermore, the rate of
      pyrophosphorolytic excision of TFV from PPT sequence was 21-fold higher than that
      for the PBS sequence. However, the addition of efavirenz, nonnucleoside reverse
      transcriptase inhibitor (NNRTI), to the removal reaction effectively inhibits the
      TFV excision from both primers by forming a stable complex that would leave TFV
      inaccessible for excision. These results illuminate the degree of primer-template
      sequence contribution on TFV removal as well as increase our understanding of the
      molecular mechanism for the beneficial effects of widely used combinations of
      antiretroviral regimens in the context of synergistic antiviral activity and drug
      resistance.

PMID- 22664236
TI  - Effects on maribavir susceptibility of cytomegalovirus UL97 kinase ATP binding
      region mutations detected after drug exposure in vitro and in vivo.
AB  - Resistance to the experimental human cytomegalovirus (CMV) UL97 kinase inhibitor
      maribavir has been mapped to UL97 mutations at codons 353, 397, 409 and 411, in
      the kinase ATP-binding region, and to mutations in the UL27 gene. We studied the
      maribavir susceptibility phenotypes of additional UL97 mutations observed in
      vitro and in clinical trials, and the effect of simultaneous mutation in both
      UL97 and UL27. In vitro selection under maribavir identified a new locus of UL97
      mutation within the conserved kinase p-loop (L337M), which conferred low grade
      maribavir resistance (3.5-fold increased EC50) without ganciclovir cross
      resistance. During maribavir Phase III CMV prevention clinical trials, three
      previously unknown UL97 sequence variants were detected in plasma samples after
      27-98 days of drug exposure (I324V, S334G and S386L). These variants did not
      confer any drug resistance despite proximity to mutations that confer maribavir
      resistance. The UL27 resistance mutation R233S, when added to strains containing
      UL97 mutations L337M or V353A, doubled their maribavir EC50s. These results
      expand the range of UL97 maribavir-resistance mutations into another part of the
      kinase ATP-binding region, but offer no genotypic evidence that development of
      drug resistance affected the outcomes of Phase III maribavir clinical trials
      after drug exposure of up to 14 weeks. There is a potential for increased
      maribavir resistance in UL27-UL97 double mutants.

PMID- 22664238
TI  - Preferential killing of triple-negative breast cancer cells in vitro and in vivo
      when pharmacological aggravators of endoplasmic reticulum stress are combined
      with autophagy inhibitors.
AB  - The cellular processes of autophagy and endoplasmic reticulum stress (ERS) appear
      to be interconnected, and it has been proposed that autophagy may serve to reduce
      ERS via removal of terminally misfolded and aggregated proteins. Conversely,
      there are indications that blockage of autophagy may increase ERS. Based on
      earlier work demonstrating that pharmacologically aggravated ERS can result in
      tumor cell killing, we investigated whether blockage of autophagy would enhance
      this effect in a therapeutically useful manner. We therefore combined chloroquine
      (CQ), a pharmacological inhibitor of autophagy, with other drugs known to act as
      ERS aggravators (ERSA), namely nelfinavir (an HIV protease inhibitor) and
      celecoxib (a cyclooxygenase-2 inhibitor) or its non-coxib analog 2,5-dimethyl
      celecoxib (DMC), and investigated combination drug effects in a variety of breast
      cancer cell lines. We found that the addition of CQ resulted in synergistic
      enhancement of tumor cell killing by ERSA compounds, particularly in triple
      negative breast cancer (TNBC) cells. This combination effect could also be
      confirmed in an in vivo model, where CQ boosted low-dose ERSA effects, resulting
      in rapid deterioration of xenografted tumors in mice. Altogether, our results
      indicate that combinations of an autophagy inhibitor with pharmacological ERSA
      (i.e. compounds that lead to ER stress aggravation) should be further explored
      for potential therapy of otherwise difficult-to-treat TNBC.

PMID- 22664237
TI  - Human endonuclease V as a repair enzyme for DNA deamination.
AB  - The human endonuclease V gene is located in chromosome 17q25.3 and encodes a 282
      amino acid protein that shares about 30% sequence identity with bacterial
      endonuclease V. This study reports biochemical properties of human endonuclease V
      with respect to repair of deaminated base lesions. Using soluble proteins fused
      to thioredoxin at the N-terminus, we determined repair activities of human
      endonuclease V on deoxyinosine (I)-, deoxyxanthosine (X)-, deoxyoxanosine (O)-
      and deoxyuridine (U)-containing DNA. Human endonuclease V is most active with
      deoxyinosine-containing DNA but with minor activity on deoxyxanthosine-containing
      DNA. Endonuclease activities on deoxyuridine and deoxyoxanosine were not
      detected. The endonuclease activity on deoxyinosine-containing DNA follows the
      order of single-stranded I>G/I>T/I>A/I>C/I. The preference of the catalytic
      activity correlates with the binding affinity of these deoxyinosine-containing
      DNAs. Mg(2+) and to a much less extent, Mn(2+), Ni(2+), Co(2+) can support the
      endonuclease activity. Introduction of human endonuclease V into Escherichia coli
      cells deficient in nfi, mug and ung genes caused three-fold reduction in mutation
      frequency. This is the first report of deaminated base repair activity for human
      endonuclease V. The relationship between the endonuclease activity and deaminated
      deoxyadenosine (deoxyinosine) repair is discussed.

PMID- 22664240
TI  - Nuclear image-guided personalized treatment and prevention of cancers.

PMID- 22664239
TI  - Tumor-specific MAGE proteins as regulators of p53 function.
AB  - Since its discovery in 1991, the knowledge about the tumor specific melanoma
      antigen gene (MAGE-I) family has been continuously increasing. Initially, MAGE-I
      proteins were considered as selective targets for immunotherapy. More recently,
      emerging data obtained from different cellular mechanisms controlled by MAGE-I
      proteins suggest a key role in the regulation of important pathways linked to
      cell proliferation. This is in part due to the ability of some MAGE-I proteins to
      control the p53 tumor suppressor. In this review, we focus on the mechanisms
      proposed to explain how MAGE-I proteins affect p53 functions.

PMID- 22664241
TI  - Radiolabeled nucleosides for predicting and monitoring the cancer therapeutic
      efficacy of chemodrugs.
AB  - Uncontrolled cell proliferation is an important hallmark of cancer. Cancer
      treatment with cytostatic chemodrugs usually results in insignificant changes in
      tumor size, and thus limits the applications of anatomical imaging modalities for
      determining the therapeutic efficacy. Positron emission tomography (PET) imaging
      with cell proliferation probes to assess the clinical outcome during or soon
      after treatment is becoming acceptable. At present, monitoring DNA synthetic
      pathways with radiolabeled nucleoside probes that are essential for cell
      proliferation has been considered a more specific approach to predict tumor
      response. Among the four nucleosides, thymidine analogues, such as (18)F-FLT,
      have undergone years of development for clinical practice, while cytidine,
      adenosine and guanosine analogues receive less attention. Recently, several
      literatures have demonstrated that PET imaging with radiolabeled cytidine and
      adenosine analogues may have potential to evaluate immune response after
      chemotherapy, and may enable the prognosis forecast. In this review, we summarize
      the results of recent preclinical and clinical studies regarding using
      radiolabeled nucleoside analogues for predicting and monitoring tumor response in
      cancer treatment. The preparation protocols of these nucleoside scintigraphic
      probes are also described.

PMID- 22664242
TI  - Radiolabeled RGD peptides as integrin alpha(v)beta3-targeted PET tracers.
AB  - Imaging techniques targeting tumor angiogenesis have been investigated for past
      decade. Of these, the radiolabeled Arg-Gly- Asp (RGD) peptide has been focused
      because it has high affinity and selectivity for integrin alpha(v)beta3. Integrin
      alpha(v)beta3 is expressed on the plasma membrane in an active status in which it
      binds its ligands and transduce signals when exposed activating external stimuli
      of tumor angiogenesis such as vascular endothelial growth factor (VEGF). Many
      linear or cyclic RGD peptides were developed for positron emission tomography
      (PET). In this review, we focused on currently developed RGD peptides as PET
      probes for non-invasive detection of integrin alpha(v)beta3 expression.

PMID- 22664243
TI  - Design of peptide imaging agents for whole-body and intraoperative molecular
      imaging.
AB  - Due to the growing toolkit of targeted contrast agents, molecular imaging
      continues to play a prominent role in the clinical care of cancer. Peptide-based
      imaging approaches are of particular significance due to their favorable
      pharmacokinetic properties, established manufacturing infrastructure, and
      documented clinical success in whole-body imaging. A logical extension of
      molecular imaging with peptides is to improve surgical outcomes in cancer through
      highly sensitive and specific probes which can be used intraoperatively. Advances
      in fluorescent imaging have resulted in various peptide labeling strategies with
      intraoperative indications. In this review, we focused on the evolving design of
      peptide imaging agents starting with the clinically used somatostatin targeting
      peptides. We then review the current synthetic approaches used for dual-labeled
      agent development and offer perspectives on optimal protection schemes that can
      be used for multimodal probe development.

PMID- 22664244
TI  - Positron emission tomography radiopharmaceuticals for sex steroid hormone
      receptor imaging.
AB  - Understanding the expression of tumor specific receptors is important not only
      for tumor diagnosis but also for planning the strategy for patient treatment.
      Tumor receptor has been one of the most critical targets for treatment in cancer
      such as breast, prostate and thyroid cancers. Positron emission tomography (PET)
      is a part of molecular imaging techniques based on detecting the
      radiopharmaceuticals that can capture functional or phenotypic changes associated
      with pathology. The advantages of detecting tumor specific receptors by PET are
      its non-invasiveness, providing comprehensive information about receptor
      expression, avoiding the sampling errors, selecting strategy for the treatment of
      patients and monitoring tumor response to therapy. Hormonal therapy plays a major
      role in cancer treatment. Therefore, we review the PET radiopharmaceuticals for
      sex steroid hormone receptor imaging in this article.

PMID- 22664245
TI  - Amino Acid transporter-targeted radiotracers for molecular imaging in oncology.
AB  - Amino acids are required for sustenance of continuous uncontrolled growth of
      tumor cells, and upregulation of amino acid transporter expression has often been
      observed in tumor cells to facilitate their accelerated rates of amino acid
      uptake. Therefore, amino acid transporters have promise as ideal targets for
      tumor imaging. In fact, many natural and artificial amino acids have been
      radiolabeled for positron emission tomography (PET) and single-photon emission
      computed tomography (SPECT) imaging of tumor. In this article, we review the
      classification, molecular biology, and pharmacological relevance of amino acid
      transport systems. In addition, we discuss the chemistry, radiochemistry, current
      clinical applications, and future prospects for the use of radiolabeled amino
      acid-based probes for PET and SPECT imaging in oncology for each category of
      radionuclide.

PMID- 22664246
TI  - Radiolabelled agents for PET imaging of tumor hypoxia.
AB  - Hypoxia has been observed in a variety of human tumor types and evaluating tumor
      hypoxia is important because it increases resistance to radiotherapy and
      chemotherapy by inducing proteomic change that allow the tumor cell to survive in
      their hypoxic environment. One of the major proteomic changes is HIF-1
      expression, and HIF-1 has become a target for anti-cancer drugs development
      because of its central role in hypoxia-mediated aggressiveness of tumor cells and
      their resistance to therapy. Since tumor hypoxia is a key mechanism that leads to
      resistance of treatment, a large number of challenges for hypoxia imaging
      including magnetic resonance, optical, and nuclear imaging have been reported.
      These hypoxia imaging techniques may have potential in selecting cancer patients
      who would benefit from treatments that overcome the presence of hypoxia. Hypoxia
      imaging could also be used to document whether or not and the extent to which
      reoxygenation of tumors occurs during cancer treatment. One of key requirements
      of ideal method for imaging hypoxia is that the method should be non-invasive.
      From an imaging perspective, PET is also one of leading tools for imaging hypoxia
      because of its high spatial resolution, high sensitivity, and advantages for
      visualizing molecular events in living human tissue. In this review, PET-based
      radiopharmaceuticals including (18)F-FMISO, (18)F-FETNIM, (18)F-FAZA, and
      radioactive Cu-ATSM were summarized from published studies about radiosyntheses,
      pre-clinical data, and clinical data, which are the lead contenders for human
      application.

PMID- 22664247
TI  - Bone target radiotracers for palliative therapy of bone metastases.
AB  - The skeleton is one of the most common organs affected by metastatic cancer, and
      bone metastases often cause severe pain, which significantly affects quality of
      life. Internal radiotherapy using specifically localized bone-seeking
      radiopharmaceuticals has proven to be an effective alternative and shows fewer
      side effects than those associated with other forms of treatment. In this review
      article, we highlight not only radiopharmaceuticals, which have been approved for
      the palliation of bone metastases but also boneseeking radiolabeled compounds
      under investigation in basic research. Specifically, we review the efficacy and
      prospects of phosphorus- 32, strontium-89 chloride, samarium-153-EDTMP, rhenium
      186/188-HEDP, rhenium-186/188-complex conjugated bisphosphonate compounds,
      yttrium-90-DOTA conjugated bisphosphonate, rhenium-186/188-DMSA, radium-223
      chloride, thorium-227-EDTMP, thorium-227-DOTMP, and lead/bismuth-212-DOTMP.

PMID- 22664248
TI  - Molecular imaging kits for hexosamine biosynthetic pathway in oncology.
AB  - Noninvasive imaging assessment of tumor cell proliferation could be helpful in
      the evaluation of tumor growth potential, the degree of malignancy, and could
      provide an early assessment of treatment response prior to changes in tumor size
      determined by computed tomography (CT), magnetic resonance imaging (MRI),
      Positron emission tomography (PET), Single-Photon emission computed tomography
      (SPECT) or ultrasonography, respectfully. Understanding of tumor proliferative
      activity, in turn, could aid in the selection of optimal therapy by estimating
      patient prognosis and selecting the proper management. PET/CT imaging of (18)F
      fluoro-2-deoxy-glucose (FDG) is recognized as a technology for diagnosing the
      presence and extent of several cancer types. Recently, radiolabeled glucosamine
      analogues were introduced as a promising SPECT agent to complement FDG imaging to
      increase specificity and improve the accuracy of lesion size in oncology
      applications. Radiolabeled glucosamine analogues were developed to localize in
      the nuclear components of cells primarily via the hexosamine biosynthetic pathway
      whereas glucose localizes in the cytoplasm of cells through the glycolytic/TCA
      pathway. This paper reviews novel kit-based radiolabeled glucosamine analogues
      for metabolic imaging of tumor lesions. The novel radiolabeled glucosamine
      analogues may increase the specificity in oncology applications and can influence
      patient diagnosis, planning and monitoring of cancer treatment.

PMID- 22664249
TI  - The role of EGFR tyrosine kinase inhibitors in the first-line treatment of
      advanced non small cell lung cancer patients harboring EGFR mutation.
AB  - Lung cancer continues to be the leading cause of cancer death worldwide. Among
      lung cancers, 80% are classified as nonsmall- cell lung cancer (NSCLC) and are
      mostly diagnosed at an advanced stage (either locally advanced or metastatic
      disease). In the last years, the discovery of the pivotal role in tumorigenesis
      of the Epidermal Growth Factor Receptor (EGFR) has provided a new class of
      targeted therapeutic agents: the EGFR tyrosine kinase inhibitors (EGFR-TKIs).
      Since the first reports of an association between somatic mutations in EGFR exons
      19 and 21 and response to EGFR-TKIs, treatment of advanced NSCLC has changed
      dramatically. Histologic profile, clinical characteristics, and mutational
      profile of lung carcinoma have all been reported as predictive factors of
      response to EGFR-TKIs and other targeted therapies. In advanced NSCLC patients
      harboring EGFR mutations, the use of EGFR TKIs in first-line treatment has
      provided an unusually large progression-free survival (PFS) benefit with a
      negligible toxicity when compared with cytotoxic chemotherapy in phase III
      randomized trials. Considering the findings regarding the excellent benefit and
      better safety profile of EGFR TKIs in EGFR mutation positive patients, these
      targeted therapeutic agents can be now considered as first-line treatment in this
      setting of patients. This review will discuss the new evidences in the role of
      EGFR-TKIs in the first-line treatment of advanced NSCLC and their implication in
      the current clinical decision-making.

PMID- 22664250
TI  - Sulfonyl group-containing compounds in the design of potential drugs for the
      treatment of diabetes and its complications.
AB  - Sulfonyl group-containing compounds constitute an important class of
      therapeutical agents in medicinal chemistry presumably because of the tense
      chemical structure and functionality of the sulfonyl, which could not only form
      hydrogen bonding interactions with active site residues of biological targets but
      also, as incorporated into core ring structure, constrain the side chains and
      allowed their specific conformations that fit the active sites. This review
      focuses on sulfonamides and sulfones, which cover more than 40 series and are
      associated with at least 10 potential pharmaceutical targets in pathways of
      glucose metabolism and insulin signaling. A large number of such compounds have
      been reported as pharmaceuticals every year in the last decade. In particular,
      increasing studies suggest that sulfonamides and sulfones play a key role in the
      design of pharmaceutical agents with potential application for the treatment of
      diabetes and its complications. First, they are inhibitors of a variety of
      enzymes including 11beta-hydroxysteroid dehydrogenase type 1, alpha- glucosidase,
      carnitine palmitoyltransferase and cytosolic phosphoenolpyruvate carboxykinase,
      and in turn involved in the regulation of the metabolism of glucose. In addition,
      they are active as activators of glucokinase and as antagonists of ghrelin
      receptors. These enzyme and receptors are tightly associated with the regulation
      of glucose metabolism and the improvement of insulin resistance. Secondly,
      sulfonamides and sulfones act in the insulin secretion. As agonists, they
      activate insulin receptor tyrosine kinase and thus increase insulin sensitivity.
      Moreover, they as inhibitors suppress protein tyrosine phosphatase 1B and
      dipeptidyl peptidase IV, and thus normalize the insulin signaling pathway.
      Finally, a number of sulfonamides and sulfones are inhibitors of aldose
      reductase, which have been linked to diabetic complications.

PMID- 22664252
TI  - MicroRNA profiling as a tool for pathway analysis in a human in vitro model for
      neural development.
AB  - MicroRNAs (miRNA) are a recently recognised class of small, non-coding RNAs
      involved in the post-transcriptional regulation of gene expression and with
      crucial implication for mammalian development. In particular, they play key roles
      in neuronal development, from early neurogenesis to neuronal differentiation and
      synaptic development, and also in in vitro systems. The detection of embryotoxic
      hazards in the preclinical phase is still a challenge, often due to species
      species variations. In this study we analysed whether miRNA expression profiles
      in a human pluripotent cell model can be a helpful tool for a more mechanistic
      approach to pharmacology and toxicology. Differentiating human pluripotent cells
      were repeatedly treated with non-cytotoxic doses of methylmercury chloride
      (MeHgCl), a well known brain developmental toxicant. The expression of proteins,
      mRNA and miRNAs were used to monitor successful neural differentiation.
      Significant changes in the expression of 12 miRNAs were detected. By using
      available bioinformatics tools, we obtained validated and predicted targets for
      the identified miRNAs, on which we performed functional clustering analysis.
      Through this approach, we identified several terms and functional clusters
      associated with neural development, together with indicators of general toxic
      effect, such as apoptosis or stress response-related genes. Interestingly, our
      results also suggest a previously undiscovered association between MeHgCl and the
      ubiquitin-proteasome protein degradation pathway. Although further investigations
      are needed, our results suggest that miRNA expression analysis is a powerful tool
      in pathway-oriented toxicity and could improve early-phase hazard assessments.

PMID- 22664253
TI  - A genome-wide transcriptome profiling reveals the early molecular events during
      callus initiation in Arabidopsis multiple organs.
AB  - Induction of a pluripotent cell mass termed callus is the first step in an in
      vitro plant regeneration system, which is required for subsequent regeneration of
      new organs or whole plants. However, the early molecular mechanism underlying
      callus initiation is largely elusive. Here, we analyzed the dynamic transcriptome
      profiling of callus initiation in Arabidopsis aerial and root explants and
      identified 1342 differentially expressed genes in both explants after incubation
      on callus-inducing medium. Detailed categorization revealed that the
      differentially expressed genes were mainly related to hormone homeostasis and
      signaling, transcriptional and post transcriptional regulations, protein
      phosphorelay cascades and DNA- or chromatin-modification. Further
      characterization showed that overexpression of two transcription factors, HB52 or
      CRF3, resulted in the callus formation in transgenic plants without exogenous
      auxin. Therefore, our comprehensive analyses provide some insight into the early
      molecular regulations during callus initiation and are useful for further
      identification of the regulators governing callus formation.

PMID- 22664251
TI  - Influence of a novel inhibitor (UM8190) of prolylcarboxypeptidase (PRCP) on
      appetite and thrombosis.
AB  - Preclinical pharmacological characterization of a novel inhibitor (UM8190) of
      prolylcarboxypeptidase (PRCP) was investigated. We synthesized and evaluated a
      library of proline-based analogs as prospective recombinant PRCP (rPRCP)
      inhibitors and inhibitors of PRCP-dependent prekallikrein (PK) activation on
      human pulmonary artery endothelial cells (HPAEC). Among the newly synthesized
      compounds, UM8190 was further characterized in vivo using methods that
      encompassed a mouse carotid artery thrombosis model and animal model of food
      consumption. (S)-N-dodecyl-1-((S)-pyrrolidine-2-carbonyl) pyrrolidine-2
      carboxamide [Compound 3 (UM8190)] was selected for further evaluation from the
      initial assessment of its PRCP inhibitory action (K(i)= 43 MUM) coupled with its
      ability to block PRCP-dependent PK activation on HPAEC (K(i)= 34 MUM). UM8190
      demonstrated excellent selectivity against a panel of carboxypeptidases and
      serine proteases and blocked bradykinin (BK) generation and BK-induced
      permeability by 100%, suggesting that it may be useful in preventing the local
      production of large amounts of BK. Furthermore, UM8190 showed an anorexigenic
      effect when systemically administered to fasted mice, reducing food intake in a
      dose- and time-dependent manner. In a mouse carotid artery thrombosis model, it
      also demonstrated an antithrombotic effect. UM8190 is a selective PRCP inhibitor
      and it may represent a new anorexigenic, and antithrombotic drug, that works by
      inhibiting PRCP-mediated mechanisms.

PMID- 22664254
TI  - Evaluation of the leachability of heavy metals from cement-based materials.
AB  - A new leaching test on comminuted (0.125-2.0mm gradation) cementitious matrices,
      designated as Modified-Pore Water (M-PW) test, was developed to evaluate the
      effect of varying leachate pH (4-12.8) and/or liquid-to-solid, L/S, ratio (0.6-50
      dm(3)/kg) on the availability factor, F(AV), of heavy metals. The M-PW test was
      applied to leaching of lead and zinc ions from ground Portland cement mortar
      incorporating Municipal Solid Waste Incinerator (MSWI) fly ash. Correlation of M
      PW test results (F(AV)-L/S data) allowed the determination of the pore-liquid
      availability factor, F(AVP), at different leachate pHs. These F(AVP) values were
      utilized, in conjunction with a kinetic pseudo-diffusional model, to evaluate the
      leaching behavior of monolithic mortar specimens subjected to dynamic leaching
      tests (constant leachant pH 4 or 6).A good agreement was found between the
      effective diffusion coefficients, D(e), of lead and zinc ions calculated by such
      a methodological approach and those obtained from recognized microstructural
      models. In contrast, no satisfactory agreement was found when these D(e) values
      were compared with the ones calculated from the results of other availability
      tests on granular solid samples (NEN 7341 and AAT tests).

PMID- 22664256
TI  - Drinking water obtaining by nanofiltration from waters contaminated with
      glyphosate formulations: process evaluation by means of toxicity tests and
      studies on operating parameters.
AB  - Glyphosate formulations toxicity depends on all its components but commercial
      products only specify the active principle in their label. To treat contaminated
      waters and to verify if the unknown components which add toxicity have been
      removed represent a challenge. Nanofiltration and permeate analysis by toxicity
      tests with fish are an interesting alternative to evaluate the process. Permeates
      of solutions with concentrations five times above the lethal doses (48 mg/l) did
      not present toxicity, pointing that all toxic compounds were removed at the same
      time. Glyphosate rejection over an 80% despite its molecular weight is lower than
      membrane MWCO, this could be associated to a predominant Donnan exclusion
      mechanism, combined with dielectric exclusion due to the solute high charge
      density. Glyphosate concentration did not show any effect over rejection. It
      increased when pressure was incremented from 2.5 to 4 bar and then remained
      constant in a 4-10 bar range. Because of dissociation of the glyphosate and the
      surface charged of the membrane depend on pH value, the rejection increase from
      72.5 to 92.5% when pH increase from 4 to 8.5. Studies with river water showed the
      same behavior with a slight decrease in rejection.

PMID- 22664255
TI  - Studying arsenite-humic acid complexation using size exclusion chromatography
      inductively coupled plasma mass spectrometry.
AB  - Arsenic (As) can form complexes with dissolved organic matter (DOM), which
      affects the fate of arsenic in waste sites and natural environments. It remains a
      challenge to analyze DOM-bound As, in particular by using a direct
      chromatographic separation method. Size exclusion chromatography (SEC) hyphenated
      with UV spectrophotometer and inductively coupled plasma mass spectrometry (ICP
      MS) was developed to characterize the complexation of arsenite (As(III)) with
      DOM. This SEC-UV-ICP-MS method is able to differentiate As(III)-DOM complexes
      from free As species and has the advantage of direct determination of both free
      and DOM-bound As(III) through mild separation. The suitability of this method for
      studying As(III)-DOM complexation was demonstrated by its application, in
      combination with the Scatchard plot and nonlinear regression of ligand binding
      model, for characterizing As(III) complexation with humic acid (HA) in the
      absence or presence of natural sand. The results suggest that, consistent with
      polyelectrolytic nature of HA, the As(III)-HA complexation should be accounted
      for by multiple classes of binding sites. By loosely classifying the binding
      sites into strong (S1) and weak (S2) sites, the apparent stability constants (Ks)
      of the resulting As-DOM complexes were calculated as logK(s1) = 6.5-7.1 while
      logK(s2) = 4.7-5.0.

PMID- 22664257
TI  - De-conjugation behavior of conjugated estrogens in the raw sewage, activated
      sludge and river water.
AB  - The fate and behavior of estrone-3-sulfate (E1-3S), estradiol-3-sulfate (E2-3S),
      estrone-3-glucuronide (E1-3G) and estradiol-3-glucuronide (E2-3G) were studied in
      raw sewage, activated sludge and river water using microcosms. The glucuronide
      conjugates had a half-life of 0.4h in raw sewage, yielding 40-60% of their free
      estrogens. Field observations at three activated sludge processes suggested
      complete transformation of the glucuronide conjugates in the sewer. In river
      water glucuronide conjugates half-lives extended to over 2d yielding 60-100% of
      their free parent estrogens. Transformation of the sulfate conjugates in raw
      sewage and river water was slow with little formation of the parent estrogens.
      Sulfate conjugates could readily be detected in sewage influent in the field
      studies. In activated sludge the sulfate conjugates had half-lives of 0.2h with
      the transient formation of 10-55% of the free parent estrogens. Field studies
      indicated transformation of sulfate conjugates across the sewage treatment,
      although a proportion escaped into the effluent. These results broadly support
      the view that glucuronide conjugates will be entirely transformed within the
      sewer largely to their parent estrogens. The sulfate conjugates may persist in
      raw sewage and river water but are transformable in activated sludge and, in the
      case of E2-3S, reform a high proportion of the parent estrogen.

PMID- 22664258
TI  - Biodegradability enhancement of wastewater containing cefalexin by means of the
      electro-Fenton oxidation process.
AB  - The comparative degradation behavior of cefalexin (CLX) using advanced oxidation
      processes (AOPs) with the aim of improving CLX biodegradability was studied.
      Among the AOPs used, RuO(2)/Ti anodic oxidation (AO), AO in the presence of
      electro-generated H(2)O(2) (AO-H(2)O(2)), and the electro-Fenton (EF) process,
      the EF process was the most effective. In the EF process an activated carbon
      fiber (ACF) was used as a cathode. Different input variables, including catalyst
      concentration, pH, and current density were evaluated to find the optimum
      conditions for the EF. The most suitable operational conditions were as follows:
      a current density of 6.66 mA/cm(2), a pH of 3, and a concentration of 1 mM of
      Fe(2+) as the catalyst. Different CLX concentrations were analyzed as well of
      different reaction times to assess the degree of mineralization. The change in
      biodegradability was evaluated by the BOD(5)/COD and the BOD(14)/COD ratios. The
      EF did not effectively remove the COD, but removed enough to achieve suitable
      biodegradability for a further biological process.

PMID- 22664259
TI  - Modified granulation of red mud by weak gelling and its application to
      stabilization of Pb.
AB  - This study presents a novel modification of red mud (RM) with cementitious
      materials by rotary drum granulation under partial hydration. Admixtures and
      surfactants were applied to improve the microspore structure of red mud-based
      granules in order to stabilize Pb steadily. Through XRD and SEM-EDS analyses, it
      was demonstrated that calcite, the main alkali in RM, was partially concreted and
      coated. Compared to pH 12.47 for RM, the lowest pH of the granules was 10.66
      implying that the release of OH(-) from hydrolysis and decomposition was
      decreased. Based on stabilization of Pb, influence on soil properties and forming
      qualities, composition of the optimum granule PSP was determined as 5% cement, 5%
      gypsum, 1% rice straw, and 0.1% emulsifier OP-10. Within a 90 d remediation,
      immobilization of ionic Pb in a 500 mg kg(-1) Pb-contaminated artificial soil was
      9.85 mg kg(-1) at day 30 with 5% PSP2 as substitute. Furthermore, the reverse
      increase diminished as the final concentration was 11.13 mg kg(-1) while it was
      14.25 mg kg(-1) by RM. The increase of residual Pb was 122.61%, which was better
      than the 83.92% of RM. Particularly, the highest pH in mine soil was 11.09 at day
      1 with RM, but the decrease of ionic Pb was 46.26%. Meanwhile, a significant
      deviation from the control soil zeta-potential lasted longer and the recovery was
      more difficult, as compared to the granules. Therefore, a granulated modification
      of RM is shown to be very important when aiming at steady release of OH(-) to
      improve the later stabilization of Pb.

PMID- 22664260
TI  - Separation of platinum and rhodium from chloride solutions containing aluminum,
      magnesium and iron using solvent extraction and precipitation methods.
AB  - The solvent extraction and precipitation methods have been used to develop a
      process to separate platinum and rhodium from a synthetic chloride solutions
      containing other associated metals such as (mg/L): Pt-364, Rh-62, Al-13880, Mg
      6980, Fe-1308 at <1M HCl acidity. At pH 3.4, the quantitative precipitation of Al
      and Fe was achieved using 10 wt% Na(3)PO(4).12H(2)O, with ~4% loss of Pt and Rh
      due to adsorption phenomenon. The selective separation of platinum was carried
      out with 0.01 M Aliquat 336 (a quaternary ammonium salt) at an aqueous to organic
      ratio (A/O) of 3.3 in two stages. Stripping of Pt from loaded organic (LO) at O/A
      ratio 6 with 0.5 M thiourea (tu) and HCl indicated that ~99.9% stripping
      efficiency. In stripping studies, needle like crystals of Pt were found and
      identified as tetrakis (thiourea) platinum (II) chloride ([Pt(tu)(4)]Cl(2)). The
      selective precipitation of rhodium was performed with (NH(4))(2)S from platinum
      free raffinate with a recovery of >99%.

PMID- 22664261
TI  - A GIS-based generic real-time risk assessment framework and decision tools for
      chemical spills in the river basin.
AB  - This paper presents a generic framework and decision tools of real-time risk
      assessment on Emergency Environmental Decision Support System for response to
      chemical spills in river basin. The generic "4-step-3-model" framework is able to
      delineate the warning area and the impact on vulnerable receptors considering
      four types of hazards referring to functional area, societal impact, and human
      health and ecology system. Decision tools including the stand-alone system and
      software components were implemented on GIS platform. A detailed case study on
      the Songhua River nitrobenzene spill illustrated the goodness of the framework
      and tool Spill first responders and decision makers of catchment management will
      benefit from the rich, visual and dynamic hazard information output from the
      software.

PMID- 22664262
TI  - Methacrylate copolymers with pendant piperazinedione-sensing motifs as
      fluorescent chemosensory materials for the detection of Cr(VI) in aqueous media.
AB  - A fluorogenic sensory film, or dense membrane, capable of detecting Cr(VI),
      Fe(III), and Hg(II) in water was prepared. The film was prepared by a bulk
      radical polymerization of different comonomers, one of which contained a
      piperazinedione motif as sensory fluorophore. The film exhibited gel-like
      behavior and was highly tractable, even after being swollen in water. The sensing
      conditions were chosen to overcome interference from iron and mercury cations,
      giving rise to a material with a detection limit of 1 ppb for Cr(VI).

PMID- 22664263
TI  - Organ-dependent oxylipin signature in leaves and roots of salinized tomato plants
      (Solanum lycopersicum).
AB  - Oxylipins have been extensively studied in plant defense mechanisms or as signal
      molecules. Depending on the stress origin (e.g. wounding, insect, pathogen), and
      also on the plant species or organ, a specific oxylipin signature can be
      generated. Salt stress is frequently associated with secondary stress such as
      oxidative damage. Little is known about the damage caused to lipids under salt
      stress conditions, especially with respect to oxylipins. In order to determine if
      an organ-specific oxylipin signature could be observed during salt stress, tomato
      (Solanum lycopersicum cv. Money Maker) plants were submitted to salt stress (100
      mM of NaCl) for a 30-d period. A complete oxylipin profiling and LOX related-gene
      expression measurement were achieved in leaves and roots. As expected, salt
      stress provoked premature senescence in leaves, as revealed by a decrease in
      photosystem II efficiency (F(v)/F(m) ratio) and sodium accumulation in leaves. In
      roots, a significant decrease in several oxylipins (9- and 13-hydro(pero)xy
      linole(n)ic acids, keto and divinyl ether derivatives) was initiated at day 5 and
      intensified at day 21 after salt treatment, whereas jasmonic acid content
      increased. In leaves, the main changes in oxylipins were observed later (at day
      30), with an increase in some 9- and 13-hydro(pero)xy linole(n)ic acids and a
      decrease in some keto-derivatives and in jasmonic acid. Oxylipin enantiomeric
      characterization revealed that almost all compounds were formed enzymatically,
      and therefore a massive auto-oxidation of lipids that can be encountered in
      abscission processes can be excluded here.

PMID- 22664264
TI  - Factors affecting fertility after cervical insemination with cooled semen in meat
      sheep.
AB  - Field results of 18,328 cervical artificial inseminations (AI) with cooled semen
      in Rasa Aragonesa meat sheep under field conditions in north-eastern Spain AI
      were analyzed. Logistic regression procedures were used including fertility at AI
      as the dependent variable (measured by lambing, 0 or 1) and year, month of AI,
      farm, hours between extraction and insemination, number of ewes inseminated in a
      set of AI, parity, lambing-treatment interval, total number of synchronization
      treatment per ewe, inseminating ram and AI technician as independent factors.
      Previous parturitions, lambing-AI interval, month, farm, inseminating ram and
      technician were factors with significant impact on AI fertility. Based on the
      odds ratio, the likelihood of pregnancy decreased: in ewes with more than five
      previous parturitions (by a factor of 0.87, 0.79 and 0.66 for the 6th, 7th and
      >=8 parturitions, respectively); in ewes with lambing-AI interval higher than 240
      days (by a factor of 0.8); and for inseminations performed during the spring
      period, (March, April, May and June, 0.70, 0.76, 0.66, and 0.76, respectively).
      We noted a higher fertility in seven inseminating rams (odds ratios between 1.4
      and 1.7) and lower in two rams (odds ratios between 0.6 and 0.7). Of the 17 AI
      technicians, two were related to fertilities improved by odds ratio of 1.6, and
      1.30, whereas two technicians were attributed fertility rates reduced by odds
      ratios of 0.68 and 0.40. These findings should be taken into account to evaluate
      the AI technique performance and make decisions to enhance fertility results.

PMID- 22664265
TI  - Fear conditioning can contribute to behavioral changes observed in a repeated
      stress model.
AB  - Repeated exposure to laboratory stressors often results in behavioral changes
      that are commonly referred to as depressive-like behaviors. Here, we examined the
      contribution fear conditioning may play in altering an animals' behavior in a
      repeated stress paradigm. Fischer rats were exposed daily to different stressors
      in a complex environment (context A). After four days of stressor exposure,
      exploratory behavior (10 min in new cage) and social interaction (5 min with
      juvenile) were tested on day 5 in either the same environment or a new
      environment (context B). Rats showed decreased exploration and social interaction
      when tested in context A compared to control rats or rats tested in context B.
      Additionally, chronic infusion of propranolol (beta-adrenergic receptor
      antagonist that crosses the blood-brain barrier), but not nadolol (beta
      adrenergic receptor antagonist that does not readily cross the blood-brain
      barrier), prevented the behavioral changes following repeated stressor exposure.
      Propranolol treatment did not affect the acute or chronic elevation of
      corticosterone, the decrease in body weight gain, or adrenal hypertrophy observed
      in animals exposed to stress. These data demonstrate that conditioned fear
      responses can contribute to behavioral changes in a repeated stress paradigm.
      Additional studies revealed, Sprague-Dawley rats do not demonstrate decreased
      exploration or social interaction when testing occurs in the same context as
      repeated stressor exposure suggesting Fischer rats may have a greater propensity
      to associate distal cues with aversive events in a complex environment. This may
      be due to greater stress responses in Fischer animals that are known to enhance
      consolidation of emotionally arousing events.

PMID- 22664266
TI  - Protein tag-mediated conjugation of oligonucleotides to recombinant affinity
      binders for proximity ligation.
AB  - While antibodies currently play a dominant role as affinity reagents in
      biological research and for diagnostics, a broad range of recombinant proteins
      are emerging as promising alternative affinity reagents in detection assays and
      quantification. DNA-mediated affinity-based assays, such as immuno-PCR and
      proximity ligation assays (PLA), use oligonucleotides attached to affinity
      reagents as reporter molecules. Conjugation of oligonucleotides to affinity
      reagents generally employs chemistries that target primary amines or cysteines.
      Because of the random nature of these processes neither the number of
      oligonucleotides conjugated per molecule nor their sites of attachment can be
      accurately controlled for affinity reagents with several available amines and
      cysteines. Here, we present a straightforward and convenient approach to
      functionalize recombinant affinity reagents for PLA by expressing the reagents as
      fusion partners with SNAP protein tags. This allowed us to conjugate
      oligonucleotides in a site-specific fashion, yielding precisely one
      oligonucleotide per affinity reagent. We demonstrate this method using designed
      ankyrin repeat proteins (DARPins) recognizing the tumor antigen HER2 and we apply
      the conjugates in different assay formats. We also show that SNAP or CLIP tags,
      expressed as fusion partners of transfected genes, allow oligonucleotide
      conjugations to be performed in fixed cells, with no need for specific affinity
      reagents. The approach is used to demonstrate induced interactions between the
      fusion proteins FKBP and FRB by allowing the in situ conjugated oligonucleotides
      to direct the production of templates for localized rolling circle amplification
      reactions.

PMID- 22664267
TI  - Triazole-induced gene expression changes in the zebrafish embryo.
AB  - The zebrafish embryo is considered to provide a promising alternative test model
      for developmental toxicity testing. Most systems use morphological assessment of
      the embryos, however, microarray analyses may increase sensitivity and
      predictability of the test by detecting more subtle and detailed responses. In
      this study, we investigated the possibility of relating gene expression profiles
      of structurally similar chemicals tested in a single concentration, to a complete
      transcriptomic concentration-response of flusilazole (FLU). We tested five other
      triazoles, hexaconazole (HEX), cyproconazole (CYP), triadimefon (TDF),
      myclobutanil (MYC), and triticonazole (TTC) at equipotent concentrations based on
      morphological evaluation. Results showed that every compound had a different
      degree of regulation within their anti-fungal and developmental toxicity
      pathways, steroid biosynthesis and retinol metabolism, respectively. Assuming
      that the ratio between these pathways is relevant for efficacy compared to
      developmental toxicity, we found TTC was more efficient and CYP was more toxic
      compared to the other triazoles. With the approach used in this study we
      demonstrated that gene expression data allow more comprehensive assessment of
      compound effects by discriminating relative potencies using these specific gene
      sets. The zebrafish embryo model can therefore be considered a useful vertebrate
      model providing information of relevant pathways related to anti-fungal mechanism
      of action and toxicological activity.

PMID- 22664268
TI  - Differential performance of Wistar Han and Sprague Dawley rats in behavioral
      tests: differences in baseline behavior and reactivity to positive control
      agents.
AB  - Developmental neurotoxicity (DNT) testing assesses potentially adverse effects on
      the developing nervous system. The present DNT study was conducted to generate
      historical data with the Wistar Han (WH) and Sprague Dawley (SD) rat strains,
      commonly used in Europe and the US, respectively. Potential differences between
      these strains in DNT endpoints have not been extensively investigated. Motor
      activity, startle response, learning and memory testing, and neurological
      (quantitative and qualitative) examinations were conducted using three groups of
      control, prenatally exposed (to Methylazoxymethanol [MAM] on gestation Day 15)
      and acutely treated (with IDPN, MK-801 or Chlorpromazine) animals for each
      strain. The positive controls produced clear effects in most endpoints
      investigated, with limited functional differences in baseline behavior and
      positive control sensitivity. However, SD rats were considerably more susceptible
      to MAM-induced learning and memory impairments and neurological damage. These
      data highlight differential sensitivity between the strains, which may require
      risk assessment consideration for developmental neurotoxicants.

PMID- 22664269
TI  - Triazole induced concentration-related gene signatures in rat whole embryo
      culture.
AB  - Commonly used as antifungal agents in agriculture and medicine, triazoles have
      been shown to cause teratogenicity in a diverse set of animal models. Here, we
      evaluated the dose-dependent impacts of flusilazole, cyproconazole and
      triadimefon, on global gene expression in relation to effects on embryonic
      development using the rat whole embryo culture (WEC) model. After 4 h exposure,
      we identified changes in gene expression due to triazole exposure which preceded
      morphological alterations observed at 48 h. In general, across the three
      triazoles, we observed similar directionality of regulation in gene expression
      and the magnitude of effects on gene expression correlated with the degree of
      induced developmental toxicity. Significantly regulated genes included key
      members of steroid/cholesterol and retinoic acid metabolism and hindbrain
      developmental pathways. Direct comparisons with previous studies suggest that
      triazole-gene signatures identified in the WEC overlap with zebrafish and mouse,
      and furthermore, triazoles impact gene expression in a similar manner as retinoic
      acid exposures in rat embryos. In summary, we further differentiate pathways
      underlying triazole-developmental toxicity using WEC and demonstrate the
      conservation of these response-pathways across model systems.

PMID- 22664270
TI  - The bovine oocyte in vitro maturation model: a potential tool for reproductive
      toxicology screening.
AB  - Reproductive toxicity testing according to the present guidelines requires a high
      number of animals. Therefore, the development of alternative in vitro methods is
      urgently required. The aim of the present study was to investigate the
      applicability domain of the bovine oocyte in vitro maturation assay (bIVM) to
      study female reproductive toxicology. Therefore, bovine oocytes were exposed to a
      broad set of chemicals of two distinct biological function groups: (a) affecting
      female fertility and (b) affecting embryonic development and having a broad range
      of physical and chemical properties. The endpoints evaluated were the oocyte
      nuclear maturation (progression of meiosis) and general cytotoxicity. The oocyte
      nuclear maturation was negatively affected by all compounds tested and the effect
      was observed at concentrations lower than the cytotoxic ones. The bIVM assay
      correctly predicted the classification of compounds between those predefined
      groups. Additionally, the bIVM model contributes significantly for the 3R
      principle, since no test animals are used in this assay. In conclusion, the bIVM
      is a sensitive and valuable alternative assay to identify potential chemical
      hazard on female fertility.

PMID- 22664271
TI  - Transcranial ultrasound (TUS) effects on mental states: a pilot study.
AB  - BACKGROUND/OBJECTIVE: Transcranial ultrasound (TUS) can modulate brain function.
      To assess possible TUS modulation of mental states, we investigated effects on
      subjective reports of pain and mood of sub-thermal TUS versus placebo applied to
      frontal scalp and brain of chronic pain patient volunteers. METHODS: With IRB
      approval and informed consent, subjects with chronic pain completed two visual
      analog scales for pain (NRS) and mood (VAMS/Global Affect), and their vital signs
      were recorded 10 min prior to, and 10 min and 40 min following exposure to either
      subthermal TUS (8 MHz) or placebo (in a double blind crossover study) using the
      12L-RS probe of a LOGIQe ultrasound imaging machine (General Electric, USA). A
      physician, also blinded for TUS versus placebo, applied the probe (with gel) to
      scalp over posterior frontal cortex, contralateral to maximal pain, for 15
      seconds. A second investigator operated the ultrasound machine, randomizing TUS
      versus placebo. The process was then repeated, applying the opposite modality
      (TUS or placebo). RESULTS: Subjective reports of Mood/Global Affect were improved
      10 min (P = 0.03) and 40 min (P = 0.04) following TUS compared with placebo. NRS
      pain reports slightly improved following TUS (P = 0.07) at 40 min. CONCLUSION: We
      found improvement in subjective mood 10 min and 40 min after TUS compared to
      placebo. TUS can have safe neurophysiological effects on brain function, and is a
      promising noninvasive therapy for modulating conscious and unconscious mental
      states and disorders. We suggest TUS acts via intra-neuronal microtubules, which
      apparently resonate in TUS megahertz range.

PMID- 22664272
TI  - Vitamin D receptor expression in the mucosal tissue at the gastroesophageal
      junction.
AB  - Barrett's esophagus is considered to be a precursor to adenocarcinoma and the
      information on VDR expression in normal and Barrett's esophagus is significantly
      lacking. In this study, we examined the expression of VDR in the lower esophagus
      and gastric cardia of normal and Barrett's esophagus by immunofluorescence.
      Columnar mucosa but not squamous mucosa at the gastroesophageal junction showed
      positive immunofluorescence to VDR. Submucosal glands and ducts deep to the
      normal squamous mucosa stained positive for VDR and localized in the cytoplasm
      and perinuclear regions with no nuclear staining. Interestingly, Barrett's mucosa
      stained strongly positive for VDR. Glandular structures in the mucosal layer were
      far less abundant in the Barrett's mucosa than in the normal gastric mucosa. As a
      result, fewer structures deep to the Barrett's epithelial layer stained positive
      for VDR when compared to normal gastric mucosa. These findings suggest that in
      normal esophagus VDR expression is restricted to columnar epithelium and
      glandular structures. Furthermore, strong VDR expression in Barrett's mucosa may
      indicate an increased sensitivity of this tissue to endogenous or therapeutic
      effects of Vitamin D.

PMID- 22664273
TI  - Genomic instability and p53 alterations in patients with malignant glioma.
AB  - The purpose of this study was to detect the level of genomic instability and p53
      alterations in anaplastic astrocytoma and primary glioblastoma patients, and to
      evaluate their impact on glioma pathogenesis and patients outcome. AP-PCR DNA
      profiling revealed two types of genetic differences between tumor and normal
      tissue: qualitative changes which represent accumulation of changes in DNA
      sequence and are the manifestation of microsatellite and point mutation
      instability (MIN-PIN) and quantitative changes which represent amplifications or
      deletions of existing chromosomal material and are the manifestation of
      chromosomal instability (CIN). Both types of alterations were present in all
      analyzed samples contributing almost equally to the total level of genomic
      instability, and showing no differences between histological subtypes. p53
      alterations were detected in 40% of samples, predominantly in anaplastic
      astrocytoma. The higher level of genomic instability was observed in elderly
      patients (>50 years) and patents with primary glioblastoma. Level of genomic
      instability had no impact on patients' survival, while presence of p53
      alterations seemed to be a favorable prognostic factor in this case. Our results
      indicate that extensive genomic instability is one of the main features of
      malignant gliomas.

PMID- 22664276
TI  - Entamoeba histolytica: a snapshot of current research and methods for genetic
      analysis.
AB  - Entamoeba histolytica represents one of the leading causes of parasitic death
      worldwide. Although identified as the causative agent of amebiasis since 1875,
      the molecular mechanisms by which the parasite causes disease are still not fully
      understood. Studying Entamoeba reveals insights into a eukaryotic cell that
      differs in many ways from better-studied model organisms. Thus, much can be
      learned from this protozoan parasite on evolution, cell biology, and RNA biology.
      In this review we discuss selected research highlights in Entamoeba research and
      focus on the development of molecular biological techniques to study this
      pathogen. We end by highlighting some of the many questions that remain to be
      answered in order to fully understand this important human pathogen.

PMID- 22664277
TI  - A method for making directed changes to the Fusarium graminearum genome without
      leaving markers or other extraneous DNA.
AB  - A method is described which allows exact targeted changes to the Fusarium
      graminearum genome, including changes of as little as one particular base pair to
      gene-size insertions, replacements or modifications. The technique leaves no
      other DNA in the genome, such as marker genes, and can be used serially to effect
      multiple complex changes in any desired chromosomal locations. The method is
      based on our previous finding that after transformation, DNA with homology to F.
      graminearum DNA recombines itself into the genome in a predictable manner
      involving multiple tandem copies. We designed a cloning vehicle with a built-in
      hygromycin-resistance marker (hygB) which can be used to transform the fungus,
      and with cloning sites to carry DNA with any desired genomic modifications. To
      effect a desired genomic change the sequence changes of interest are incorporated
      between two adjacent borders homologous to F. graminearum DNA which will target
      them to the desired location. This modified DNA is attached within the cloning
      sites within the vehicle. Transformants are readily obtained in which tandem
      copies of the vehicle plus insert are inserted between the two genomic border
      sequence homologues. Progeny of a transformant are subsequently screened for
      those with a decreased resistance to the antibiotic, and then for those which
      have completely lost the marker and the entire vehicle, leaving only the desired
      sequence modifications between the two genomic border sequences which were
      targeted. This method is demonstrated by exactly replacing the trichodiene
      synthase (tri5) gene coding sequence (CDS) with that of a green fluorescence
      protein (gfp) gene with no other genomic changes. This derivative was then re
      engineered to replace the gfp CDS with that of the wild type, exactly
      regenerating the original F. graminearum genome.

PMID- 22664278
TI  - Numerical investigations of the loading behaviour of a prefabricated non-rigid
      bar system.
AB  - The aim of this study has been to systematically evaluate the loading behaviour
      of a novel pre-fabricated chair-side SFI-Bar((r)) bar system supported by two
      implants using finite element (FE) analysis. Two series of FE models were created
      of the bar placed on two idealised implants and embedded in idealised bone
      segments using CAD data. In the first series, the inter-implant distance varied
      from 10 to 26mm; the second series consisted of a bar with a fixed implant
      distance of 26mm and varying horizontal fitting inaccuracy from 0.0 to 0.3mm. The
      bar was loaded vertically at 500 N. In all simulations, the regions with the
      greatest amount of stress were concentrated on the connecting elements of the bar
      and the bar itself. A slight increase in stress was observed with decreasing
      inter-implant distance. With a non-zero fitting inaccuracy, no clear correlation
      was observed between the amount of play and the stress distribution in the
      system. For a perfect fit, an obvious increase in stress was found in the implant
      and strain in the implant bed. With respect to the excessive static loading
      performed in our simulations and the resulting loading behaviour, we conclude
      that the SFI-Bar is a system suitable for clinical application.

PMID- 22664279
TI  - Vena cava filter practices of a regional vascular surgery society.
AB  - BACKGROUND: Vena cava filter (VCF) use in the United States has increased
      dramatically with prophylactic indications for placement and the availability of
      low-profile retrievable devices, which are overtaking the filter market. We
      surveyed the practice patterns of a large group of vascular surgeons from a
      regional vascular surgery society to see whether they mirrored current national
      trends. METHODS: A 17-question online VCF survey was offered to all members of
      the Southern Association of Vascular Surgery. The responses were analyzed using
      the chi(2) goodness of fit tests. RESULTS: Of the 276 members surveyed, 126 (46%)
      responded, with 118 (93%) indicating that they placed filters during their
      practice. Highly significant differences were identified with each question (at
      least P < 0.002). Regarding the inferior vena cava, the preferred permanent
      filters were the Greenfield (31%), the TrapEase (15%), the Vena Tech (5%), and a
      variety of retrievable devices (49%). Fifty percent of the respondents placed
      retrievable filters selectively; 26% always placed them; and 24% never did.
      Filters were placed for prophylactic indications <50% of the time by 63% of the
      respondents. Overall, retrievable filters (when not used as permanent filters)
      were removed <25% of the time by 64% of the respondents and <50% of the time by
      78% of the respondents. The femoral vein was the preferred access site for 84% of
      the respondents. Major complications were few but included filter migration to
      the atrium (one), atrial perforation (one), abdominal pain requiring surgical
      filter removal (two), inferior vena cava thrombosis (12 vena cava thrombosis--4
      due to TrapEase filters), strut fracture with embolization to heart or lungs
      (three Bard retrievable filters), and severe tilting precluding percutaneous
      retrieval and protection from pulmonary emboli (8 filters with severe tilt--7 of
      which were Bard). Of the respondents, 59% had never placed a superior vena cava
      filter, and 28% had placed five or fewer. CONCLUSIONS: Although VCF insertion
      overall appears safe, some complications are specific to biconical and certain
      retrievable filters. Given the low removal rate and lack of long-term experience
      with retrievable filters, routine use of these devices as permanent filters
      should be questioned. If used on a temporary basis, there should be a plan for
      filter removal at the time of implantation.

PMID- 22664280
TI  - A genetic study of chronic venous insufficiency.
AB  - BACKGROUND: Chronic venous insufficiency (CVI) is an important cause of morbidity
      in Western countries. The aim of this study is to demonstrate the heredity of
      CVI, focusing on molecular and genetic aspects of the disease. METHODS: The study
      depended on the recruitment of informative families, accurate determination of
      the phenotype of each family member, and blood sample for DNA extraction for
      genetic analysis. Each family member was invited to attend a vascular
      consultation. A genealogical tree for each recruited family was composed. Then, a
      peripheral blood sample for DNA extraction from each member of the recruited
      families was obtained for genetic evaluation. RESULTS: By the evaluation of
      genealogical trees, it was evident that CVI segregates, in all families studied,
      in an autosomal dominant mode with incomplete penetrance. In nine families
      studied, varicose veins were linked to the candidate marker D16S520 on chromosome
      16q24, which may account for the linkage to FOXC2. CONCLUSION: In our study, in
      families with affected patients with the D16S520 marker, there was evidence of
      saphenofemoral junction reflux. The fact that there is linkage to a candidate
      marker for the FOXC2 gene suggests there is a functional variant within, or in
      the vicinity of, which predisposes to varicose veins. Further studies are
      necessary to identify genes and mechanism so as to achieve better understanding
      of the genetic basis of CVI.

PMID- 22664281
TI  - The results of surgical treatment for patients with venous malformations.
AB  - BACKGROUND: The objective of this study was to estimate the outcomes of surgical
      treatment for patients with venous malformations (VMs). METHODS: We
      retrospectively reviewed the data of 48 patients who underwent surgical
      management for VMs from 1994 to 2009 at our institute. The 1-year responses to
      surgeries were classified into three groups based on the results: "remission,"
      "improvement," and "no change." RESULTS: The indications of surgeries were mass
      or swelling in 48 patients (100%), intractable pain in 11 (23%), limb length
      discrepancy in seven (15%), bleeding in three (6%), and limitation of the range
      of motion in one (2%). The locations of the VMs were head and neck in 17 patients
      (35%), abdomen and pelvis in one (2%), perineum and genitalia in three (6%),
      upper extremities in 12 (25%), and lower extremities or buttocks in 15 (31%). Of
      the 48 surgeries for radical excision and debulking, 25 (52%) resulted in
      remission, 11 (23%) in improvement, and 12 (25%) in no change. During follow-up
      (mean: 44.8 +/- 36.6 months, range: 0-111 months), recurrence after radical
      excision occurred in 10% (3 of 31) of the patients, and size increase after
      debulking surgery in 24% (4 of 17) of the patients. CONCLUSIONS: Surgical
      treatment can be an option in patients with VMs, especially with symptoms that
      cannot be managed with conservative therapy or sclerotherapy. After excisional or
      debulking surgery in patient with VMs, remission or improvement can be observed
      in 75%.

PMID- 22664282
TI  - Surgery with vascular reconstruction for soft-tissue sarcomas in the inguinal
      region: oncologic and functional outcomes.
AB  - BACKGROUND: Treatment of soft-tissue sarcomas involving the inguinal region
      remains challenging because of difficulties in achieving wide surgical margins
      due to anatomical features. The study aimed to analyze the oncologic and
      functional outcomes of wide resection with vascular reconstruction for inguinal
      soft-tissue sarcomas. METHODS: Three men and seven women were treated for
      inguinal soft-tissue sarcomas by wide surgical resection with vascular
      reconstruction. RESULTS: Arteries and veins were replaced in nine patients, and
      artery replacement alone was carried out in one patient. Femoral nerve resections
      were performed in six patients. One patient and five patients developed local
      recurrence and distant metastases, respectively. Limb salvage was achieved in 9
      of 10 patients (90%). Six patients and one patient developed vascular (arterial
      graft occlusion [n = 1], lymphedema [n = 5]) and nonvascular (hematoma [n = 1])
      complications, respectively. Five-year arterial primary patency was 77%. Five
      year disease-free and overall survival rates were 45% and 77%, respectively.
      Functional outcome scores at latest follow-up averaged 87.5% for Musculoskeletal
      Tumor Society 1993. CONCLUSIONS: En-bloc resection of major critical structures
      along with tumor and vascular reconstructions using synthetic grafts is a
      feasible option in limb salvage surgery for inguinal soft-tissue sarcomas.

PMID- 22664283
TI  - Endoluminal treatment of dissecting aortic arch aneurysm after surgical treatment
      of acute type A dissection.
AB  - BACKGROUND: The aim of this study was to evaluate the short- and midterm results
      following endovascular repair of dissecting aortic arch aneurysm after surgical
      treatment of acute type A dissection. METHODS: Between 2003 and 2010, six
      consecutive patients previously operated for acute type A dissection underwent
      endovascular repair of dissecting aortic arch aneurysm (six men, mean age: 63 +/-
      9.8 years); one of the aneurysms was ruptured. Follow-up computed tomography
      scans were performed at 1 week, at 3 and 6 months, and annually thereafter.
      RESULTS: All endografts were successfully deployed (TAG [2], Valiant [4]). All
      the patients underwent hybrid technique with supra-aortic debranching (through a
      sternotomy approach in four cases and through a cervical approach in two cases)
      and simultaneous or staged endovascular stent-grafting. During the same operative
      time, one patient underwent, on full cardiopulmonary bypass, saphenous vein
      bypass from the ascending aorta to the anterior descending coronary artery. One
      permanent neurologic event was observed. After a mean follow-up of 22.3 +/- 14.6
      months, no aortic-related mortality was observed. No cases of stent-graft
      migration or secondary rupture were observed. The ruptured aortic arch aneurysm
      presented a type I endoleak at 6 months and was successfully treated with a
      second endograft. One patient died of an unrelated cause 7 months after surgical
      repair. CONCLUSIONS: Our experience demonstrates promising potential of
      endovascular repair of dissecting aortic arch aneurysm after surgical treatment
      of acute type A dissection. The potential to diminish the magnitude of the
      surgical procedure and the consequences of aortic arch exposure, and above all
      avoiding the need for circulatory arrest, is promising and mandates further
      investigation to determine the efficacy and durability of this technique.

PMID- 22664284
TI  - Technical strategy for the endovascular management of ascending aortic
      pseudoaneurysm.
AB  - We present two cases of ascending aortic pseudoaneurysm exclusion with off-the
      shelf aortic stent grafts. The right common carotid artery was used for access to
      facilitate graft delivery. Control of graft deployment was aided using a
      compliant right atrial occlusion balloon to lower cardiac output at the time of
      deployment. Transesophageal echocardiography facilitated the sizing and
      positioning of the right atrial balloon and was used to survey the heart and
      ascending aorta on successful exclusion of the pseudoaneurysm. These simple
      maneuvers made an uncommon procedure straight forward, predictable, and
      successful.

PMID- 22664285
TI  - Eagle syndrome revisited: cerebrovascular complications.
AB  - Cervical pain caused by the elongation of the styloid process (Eagle syndrome) is
      well known to otolaryngologists but is rarely considered by vascular surgeons. We
      report two patients with cerebrovascular symptoms of Eagle syndrome treated in
      our medical center in the past year. Case 1: an 80-year-old man with acromegaly
      presented with dizziness and syncope with neck rotation. The patient was noted to
      have bilateral elongated styloid processes impinging on the internal carotid
      arteries. After staged resections of the styloid processes through cervical
      approaches, the symptoms resolved completely. Case 2: a 57-year-old man presented
      with acute-onset left-sided neck pain radiating to his head immediately after a
      vigorous neck massage. Hospital course was complicated by a 15-minute transient
      ischemic attack resulting in aphasia. Angiography revealed bilateral dissections
      of his internal carotid arteries, with a dissecting aneurysm on the right. Both
      injuries were immediately adjacent to the bilateral elongated styloid processes.
      Despite immediate anticoagulation therapy, he experienced aphasia and right
      hemiparesis associated with an occlusion of his left carotid artery. He underwent
      emergent catheter thrombectomy and carotid stent placement, with near-complete
      resolution of his symptoms. Elongated styloid processes characteristic of Eagle
      syndrome can result in both temporary impingement and permanent injury to the
      extracranial carotid arteries. Although rare, Eagle syndrome should be considered
      in the differential diagnosis in patients with cerebrovascular symptoms,
      especially those induced by positional change.

PMID- 22664286
TI  - Fibular nerve injury after small saphenous vein surgery.
AB  - Superficial nerve injuries are very common during varicose vein surgery. In
      contrast, deep nerve injuries are rare and reported especially when surgery
      involves the small saphenous vein (SSV). The deep motor nerves most commonly
      injured are the tibial nerve and the peroneal nerve, which are directly or
      indirectly affected by extrinsic compression, stretching, or healing process
      involvement. In this report, two cases of common fibular nerve injury after SSV
      stripping are described, including treatment used and patient outcomes. Nerve
      damage mechanisms, anatomy, and prevention strategies are also discussed. In
      conclusion, fibular nerve damage may occur during SSV stripping. Preventive
      measures include careful preoperative ultrasonographic investigation of the
      anatomy of the vein, determining location of the saphenopopliteal joint, and
      careful dissection far from fibular nerve and restricted to the popliteal fossa.

PMID- 22664287
TI  - Stent graft exclusion of a ruptured mycotic popliteal pseudoaneurysm complicating
      sternoclavicular joint infection.
AB  - A mycotic pseudoaneurysm of the popliteal artery is usually a consequence of
      septic embolization and often a result of bacterial endocarditis. Conventional
      treatment is surgical and avoids the placement of foreign material in infected
      sites. Here we report our treatment of a 59-year-old man who presented with a
      rupture of a mycotic pseudoaneurysm of the popliteal artery due to septic
      embolism from sternoclavicular infectious arthritis. Radiological investigations
      are included. This is the first documented case of septic arthritis complicated
      by a rupture of a mycotic popliteal false aneurysm and treated using an
      endovascular procedure. Combining endovascular stent grafts with evacuation of
      the joint abscess and antibiotic therapy can offer a safe alternative for frail
      and unstable patients.

PMID- 22664288
TI  - Pancreatitis-related abdominal aortic pseudoaneurysms treated with stent-grafts.
AB  - Endovascular treatment of pseudoaneurysms that develop as a complication of
      pancreatitis is increasingly more common. A case of a pseudoaneurysm of the
      abdominal aorta initially treated by implantation of a straight aortic stent
      graft is presented. In the 4 months after the procedure, chronic inflammation of
      the retroperitoneal space caused a further perforation on the posterior wall of
      the aorta in the area of the bifurcation, distal to the graft. Implantation of a
      bifurcated stent-graft was subsequently performed. The aneurysm was excluded,
      with the implant and peripheral arteries remaining patent.

PMID- 22664289
TI  - Subclavian artery aneurysm in Marfan syndrome.
AB  - We present a case of a left subclavian artery aneurysm in a 48-year-old man with
      Marfan syndrome. Aneurysms of the subclavian artery are rare in patients with
      Marfan syndrome. Resection of the aneurysm and interposition with a synthetic
      graft were performed through a supra- and infraclavicular incision, without
      resecting the clavicle. Histological findings were compatible with Marfan
      syndrome. In patients with Marfan syndrome, regular follow-up is important
      because of the occurrence of peripheral aneurysms other than the aorta.

PMID- 22664290
TI  - Fenestrate what you can't snorkel?
AB  - BACKGROUND: Although challenging proximal necks have limited the utility of
      standard endovascular aneurysm repair (EVAR) devices, sophisticated endovascular
      techniques have evolved in recent years for the repair of juxtarenal abdominal
      aortic aneurysms (AAAs). Among these techniques, snorkel or chimney EVAR (sn
      EVAR) and fenestrated EVAR (f-EVAR) have emerged as options for repairing
      anatomic high-risk AAAs. Unfortunately, in the United States, except in the
      context of a clinical trial or physician-sponsored device exemption, limited long
      term data exist on the treatment of juxta- and suprarenal AAAs with either sn
      EVAR or f-EVAR. Owing to these limitations, comparison of these two techniques is
      challenging, and we sought to describe a case when one was favored over the
      other. METHODS AND RESULTS: A 72-year-old man presented with an enlarging,
      asymptomatic, juxtarenal fusiform AAA (5.9 cm), a moderately enlarged right
      common iliac artery (2.8 cm), a history of oxygen-dependent chronic obstructive
      pulmonary disease, and a previous right nephrectomy. An initial sn-EVAR was
      attempted but was unsuccessful owing to the inability to deliver the "snorkel"
      covered stent via a brachial approach because of renal ostial stenosis and
      cephalad angulation of the patient's left renal artery. A subsequent f-EVAR
      approach was successfully used to repair the juxtarenal AAA while preserving
      adequate renal artery blood flow. Two-year postoperative follow-up demonstrated a
      stable endovascular repair without endoleaks, a shrinking aneurysm sac, and
      stable renal function. CONCLUSION: The sn-EVAR configuration in this case report
      was precluded by cephalad renal angulation, and the AAA was instead repaired
      using an f-EVAR approach, with good 2-year follow-up outcomes. The sn-EVAR
      strategy requires downward pointing renal arteries in addition to adequate
      brachial/axillary artery access dimensions to facilitate successful repair. With
      improving techniques and technology for either approach, anatomic specifications
      and indications for these advanced EVAR strategies will need to be delineated.

PMID- 22664291
TI  - Endovascular stent graft repair for a Salmonella-infected aneurysm of thoracic
      aorta.
AB  - Thoracic endovascular aneurysm repair using stent graft has been reported as a
      feasible and effective treatment for aortic aneurysm. However, its application
      for treating infected aortic aneurysms is still controversial and less reported.
      We report a 74-year-old male diabetic patient diagnosed with Salmonella-infected
      aortic aneurysm, who was successfully treated with endovascular stent graft
      repair followed by a 2-month course of intravenous antibiotics and long-term oral
      antibiotic therapy. Sequential computed tomography scans demonstrated the
      shrinkage of the aneurysm and no evidence of relapse 11 months later.

PMID- 22664292
TI  - Stepwise revascularization by carotid endarterectomy after balloon angioplasty
      for symptomatic severe carotid artery stenosis.
AB  - The authors report a novel stepwise carotid revascularization method to prevent
      perioperative complication. A 68-year-old man presented with left hemiparesis and
      dysarthria caused by severe stenosis of the right cervical internal carotid
      artery. According to the preoperative cerebral blood flow evaluation and plaque
      characterization, the patient was at risk for postoperative hyperperfusion and
      ischemic complications after carotid artery stenting. Initially, the patient
      underwent percutaneous angioplasty using an undersized balloon. Fifteen days
      later, the patient underwent a carotid endarterectomy. The surgical specimen
      obtained during the carotid endarterectomy showed the presence of typical
      vulnerable plaque. Of note was the complete preservation of the thin fibrous cap.
      The postoperative single-photon emission tomography images showed no signs of
      hyperperfusion, and the patient developed no neurological symptoms after each of
      the procedures.

PMID- 22664293
TI  - Acute expansion of a hospital-acquired methicillin-resistant Staphylococcus
      aureus-infected abdominal aortic aneurysm.
AB  - Infected aortic aneurysms (IAAs) are rare but can have devastating outcomes,
      particularly if diagnosis and treatment are delayed. The incidence of IAA is
      between 0.65% and 2% of all aortic aneurysms. The disease has a poor prognosis
      because these aneurysms have an increased tendency to grow rapidly and to
      rupture, and patients often have severe comorbidities and coexisting sepsis.
      Typical microorganisms associated with IAA are Salmonella, Streptococci, and
      Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus (MRSA)
      continues to emerge as a cause of serious infections, but its association with
      IAA is extremely rare. We present a rare case of infected abdominal aortic
      aneurysm caused by hospital-acquired (HA) MRSA. This case adds another
      presentation to the clinical spectrum of HA MRSA infections, and it highlights
      the problems encountered in the choice of the therapy of serious HA or health
      care-acquired infections in an era of increasing MRSA infections. We will discuss
      the clinical spectrum of HA MRSA infections as well as the problems encountered
      in the management of IAA, and will review the relevant literature.

PMID- 22664294
TI  - Incapacitating pelvic congestion syndrome in a patient with a history of May
      Thurner syndrome and left ovarian vein embolization.
AB  - BACKGROUND: The aim of this article is to report a rare case of unresolved
      incapacitating pelvic congestion syndrome (PCS) in a patient with a history of
      May-Thurner syndrome previously treated with stenting and left ovarian vein
      embolization. Additionally, this article highlights the role of pelvic venography
      in patients with PCS and reviews the coexistence. METHODS: A 32-year-old woman
      was referred to us for the evaluation of recurrent pelvic pain and dyspareunia
      requiring analgesics. Initially, she developed left lower-extremity deep vein
      thrombosis a few months after her first pregnancy. On further workup, she was
      diagnosed with May-Thurner syndrome and underwent left common iliac and left
      external iliac vein stenting. Furthermore, left ovarian vein coil embolization
      was performed for symptoms suggesting PCS at the same outside facility. The
      patient was referred to us for persistent pelvic pain approximately 1 year after
      she underwent left ovarian vein coil embolization. A diagnosis of incompletely
      resolved PCS was considered. RESULTS: Iliocaval venogram demonstrated patent left
      common iliac and external iliac venous stents in situ. Subsequent right ovarian
      venogram revealed a patent, but grossly dilated, right ovarian vein with
      retrograde flow and cross-pelvic collaterals confirming grade III PCS. Right
      ovarian vein coil embolization was performed, with excellent patient outcome.
      CONCLUSION: In the setting of a combined diagnosis of PCS and May-Thurner
      syndrome, persistent incapacitating PCS after initial iliac stenting should be
      followed with a complete pelvic venous evaluation including ovarian and left
      renal venography to rule out residual pelvic congestion secondary to any
      coexisting ovarian vein incompetencies or nutcracker syndrome.

PMID- 22664295
TI  - Endovascular treatment of an iatrogenic perforation of the internal iliac vein.
AB  - We describe the case of a 48-year-old woman who developed a pelvic abscess after
      extensive surgery for recurrent ovarian cancer. While draining the abscess, a
      massive venous bleeding occurred. The bleeding was controlled by introducing a
      Foley catheter transrectally, occluding the perforated internal iliac vein.
      However, the catheter was positioned unintentionally in the inferior vena cava,
      causing hemodynamic instability. The iatrogenic perforation of the internal iliac
      vein was managed successfully with an endovascular approach using thrombin in
      combination with balloon-induced thrombosis. If iatrogenic venous bleeding occurs
      and the placement of a stent is precluded, balloon-induced thrombosis in
      combination with thrombin injection can be used successfully.

PMID- 22664296
TI  - Aneurysm of the superior labial artery.
AB  - This is a case report of a true and dissecting aneurysm of the superior labial
      artery in a 51-year-old patient without risk factors for vascular pathology. The
      patient complained of swelling of the upper lip, mostly on the left side. A
      Doppler ultrasonography was used in the diagnosis. The definitive treatment was
      surgical resection, and the histopathological analysis confirmed the diagnosis.
      The progress of the patient was satisfactory, leaving a slight change in
      sensitivity in the area. This seems to be the first reported case of true and
      dissecting aneurysm of the superior labial artery in the medical literature.

PMID- 22664297
TI  - Endovascular central venous stenosis treatment ended with superior vena cava
      perforation, pericardial tamponade, and exitus.
AB  - Venous hypertension and outflow stenosis of arteriovenous hemodialysis access
      managed using endovascular procedures usually present a high technical success
      rate, with few complications. We reported a rare and fatal complication of
      superior vena cava perforation with pericardial tamponade 3 months after
      subclavian vein stenting. Interventional recanalization with stenting for the
      management of superior vena cava syndrome or central vein stenosis is a safe
      procedure with a low complication rate. Stent misplacement, reocclusion,
      migration, or access-related complications appear to occur most frequently.

PMID- 22664298
TI  - Effect of labeling on new vegetable dish acceptance in preadolescent children.
AB  - The aim of this study was to explore the effectiveness of a food-labeling
      strategy to introduce new versions of foods to children's diets, in natural lunch
      settings (school canteens). The proposed food involved two different types of
      vegetables: carrots (very familiar) and broccoli (less familiar), both being
      prepared and presented for choice in a 'familiar' (known) versus a 'new'
      (unknown) version. We assessed whether adding a label (either basic or model
      related) to new versions of vegetable dishes would increase the likelihood that 8
      to 11-year-old children would select the new dishes rather than the familiar
      versions. In the first condition (no label/control condition), both the familiar
      and the new versions of the vegetable dishes were presented with absence of any
      information. In the second condition (basic label condition), the new dish was
      presented accompanied by a basic label: "new carrot/broccoli recipe". In the
      third condition (model-related label condition), the new version of the dish was
      presented with a model-related label: "new carrot/broccoli recipe, Special Mix
      for Super Heroes". Results showed that children chose significantly more often
      the familiar version of the dish when no information was given (control
      condition). The addition of a descriptive label (whether basic or model-related)
      led to an increased frequency of choice for the new vegetable dish for carrots
      only, and not for broccoli. This study suggests that adding a label with the
      vegetable's name can be used to increase children's willingness to select a new
      version of a vegetable dish instead of a familiar one, at least when the
      vegetable is familiar to the children (i.e. carrots).

PMID- 22664299
TI  - Specificity of the failure to inhibit responses in overweight children.
AB  - Poor response inhibition has been associated with obesity, excessive food intake,
      and other consumptive behaviours, including alcohol use. However, the correlation
      between obesity and addictive behaviours like alcoholism is low: people who are
      obese appear to have a specific problem in restraining food intake. This would
      imply that obese people have more difficulties in inhibiting responses towards
      food, compared to other rewarding stimuli. In the present study 89 children (ages
      7-9) were tested with the stop signal task, in which responses towards food
      pictures or toy pictures had to be inhibited. Results showed that children were
      less effective in inhibiting responses towards food and percentage overweight
      predicted a lower ability to inhibit responses in general. When dichotomizing the
      sample in overweight and lean children, it appeared that overweight children were
      specifically less effective in inhibition towards food cues, compared to lean
      children. IN CONCLUSION: The results confirm weight related inhibitory problems
      and might explain the increased overeating to food cues in overweight children,
      as reported in the literature.

PMID- 22664301
TI  - Effect of different children's menu labeling designs on family purchases.
AB  - The majority of labeling studies at restaurants have focused on adults, not
      children, and utilized cross-sectional data with one menu labeling design,
      typically calorie information. The aim of this longitudinal study was to examine
      the effect of three different menu labeling designs for children's meals on total
      calories and fat selected by families. Each menu was implemented for 2months.
      Patrons' purchases were tracked from a control menu (with no nutrition
      information) through all three theoretically-based designs: calorie and fat
      information; followed by symbols denoting healthier choices; then nutrition
      bargain price. All menus were created specifically for the study. They featured
      six combination meals (pre-determined entrees and side items) and a la carte
      items (entrees and side items that could be ordered separately). Only combination
      meals contained labeling. Fixed effects models were estimated to detect changes
      in sales for each menu labeling design compared to the control. Overall, menu
      labeling did not result in a positive net effect on total calories or fat
      purchased by families, but resulted in significant shifts in purchases of
      combination and a la carte meals and healthy and unhealthy options. The most
      significant impact was seen for nutrition bargain price labeling, the last
      design.

PMID- 22664300
TI  - Gut-brain nutrient signaling. Appetition vs. satiation.
AB  - Multiple hormonal and neural signals are generated by ingested nutrients that
      limit meal size and suppress postmeal eating. However, the availability of sugar
      rich and fat-rich foods can override these satiation/satiety signals and lead to
      overeating and obesity. The palatable flavor of these foods is one factor that
      promotes overeating, but sugar and fat also have postoral actions that can
      stimulate eating and increase food preferences. This is revealed in conditioning
      studies in which rodents consume flavored solutions paired with intragastric
      sugar or fat infusions. The significant flavor preferences and increased intake
      produced by the nutrient infusions appear to involve stimulatory gut-brain
      signals, referred to here as appetition signals, that are distinct from the
      satiation signals that suppress feeding. Newly developed rapid conditioning
      protocols may facilitate the study of postoral appetition processes. 

PMID- 22664302
TI  - Characterization of the Three-Factor Eating Questionnaire scores of a young
      French cohort.
AB  - The aims of our study were to characterize the psychological dimensions of eating
      behaviour of young French adults as measured by the Three Factor Eating
      Questionnaire (TFEQ) and to analyze the association between the 3 TFEQ mean
      scores (main scales and subscales) and gender, Body Mass Index (BMI) and socio
      demographic data in this population. An online TFEQ questionnaire was used with a
      nationally representative sample of 1000 young French people (aged 20-39yrs). The
      average scores were 6.3+/-0.1 (sem) for dietary restraint, 6.0+/-0.1 for
      disinhibition and 5.0+/-0.1 for hunger. Compared to the limit commonly used in
      human food studies, young French adults were characterized by low restraint and
      low disinhibition levels. There was a significant gender effect on both restraint
      and disinhibition scores, with women showing significantly higher scores than
      men. Concerning the link between TFEQ scores and BMI, there was a significant
      effect of the BMI category on cognitive restraint, disinhibition and hunger.
      Disinhibition was the factor most strongly associated to BMI, independently of
      gender. Our results highlight both the importance of taking into account not only
      disinhibition but also cognitive restraint and the usefulness of subscales when
      studying eating behaviour and its link to body weight. We characterize the eating
      behaviour of a French cohort with criteria often chosen for healthy volunteers in
      human food studies. Consequently, we suggest new TFEQ limits (6 for cognitive
      restraint and disinhibition, 5 for hunger) lower than those traditionally used
      for this category of the population in clinical food studies.

PMID- 22664304
TI  - Group III and subtype 4 metabotropic glutamate receptor agonists: discovery and
      pathophysiological applications in Parkinson's disease.
AB  - Restoring the balance between excitatory and inhibitory circuits in the basal
      ganglia, following the loss of dopaminergic (DA) neurons of the substantia nigra
      pars compacta, represents a major challenge to treat patients affected by
      Parkinson's disease (PD). The imbalanced situation in favor of excitation in the
      disease state may also accelerate excitotoxic processes, thereby representing a
      potential target for neuroprotective therapies. Reducing the excitatory action of
      glutamate, the major excitatory neurotransmitter in the basal ganglia, should
      lead to symptomatic improvement for PD patients and may promote the survival of
      DA neurons. Recent studies have focused on the modulatory action of metabotropic
      glutamate (mGlu) receptors on neurodegenerative diseases including PD. Group III
      mGlu receptors, including subtypes 4, 7 and 8, are largely expressed in the basal
      ganglia. Recent studies highlight the use of selective mGlu4 receptor positive
      allosteric modulators (PAMs) for the treatment of PD. Here we review the effects
      of newly-designed group-III orthosteric agonists on neuroprotection,
      neurorestoration and reduction of l-DOPA induced dyskinesia in animal models of
      PD. The combination of orthosteric mGlu4 receptor selective agonists with PAMs
      may open new avenues for the symptomatic treatment of PD. This article is part of
      a Special Issue entitled 'Metabotropic Glutamate Receptors'.

PMID- 22664306
TI  - Modern management of acute myocardial infarction.
AB  - Disruption of intracoronary plaque with thrombus formation provides the
      pathophysiologic foundation for acute coronary syndromes, which comprise ST
      segment myocardial infarction, non-ST-segment myocardial infarction, and unstable
      angina. Management differs depending on whether ST-segment elevation is present,
      but the general principles of timely restoration of coronary blood flow and
      initiation of secondary prevention strategies are applicable to all patients. The
      purpose of this review is to discuss first the epidemiology, pathophysiology, and
      diagnosis of acute myocardial infarction. Risk stratification and therapy for
      patients with ST-segment elevation myocardial infarction and non-ST-segment
      elevation acute coronary syndromes are then reviewed along with diagnosis and
      management of the complications of myocardial infarction.

PMID- 22664303
TI  - Correlation of serotonin levels in CSF, platelets, plasma, and urine.
AB  - BACKGROUND: Neurotransmitter levels are best measured in the cerebrospinal fluid
      (CSF), but that requires an invasive procedure. METHODS: Samples were collected
      from humans and rats. Eighteen women age 38-51 years with fibromyalgia provided
      samples of CSF, plasma, platelets, and urine. Samples of CSF, plasma, platelets,
      and urine were also collected from Sprague-Dawley rats, adult male, 6 months old.
      One group of rats was treated with p-chlorophenylalanine to decrease their levels
      of serotonin, and another group of rats was treated with amphetamine to increase
      their levels of serotonin. Methodological improvements include: 1) the use of
      siliconized glassware, plasticware, and tubing to prevent adsorption of
      serotonin, 2) the extraction of serotonin from the CSF, plasma, and platelets, 3)
      repeated washing of the platelets with an improved buffer, and 4) early morning
      sample collection. HPLC/MS was used to measure serotonin after extraction.
      RESULTS: For serotonin, the new method of measuring platelet levels resulted in a
      very high correlation with levels of serotonin in CSF in rats (r=0.97) and humans
      (r=0.97). There were lower correlations of levels of serotonin in CSF with levels
      in plasma (r=0.77 for rats and r=0.57 in humans) and urine (r=0.67 in rats and
      r=0.62 in humans). GENERAL SIGNIFICANCE: This method of measuring serotonin
      levels in platelets results in a very strong correlation with levels in CSF, so
      in most cases platelet measurements will be preferable since it is much less
      invasive to collect. Levels of serotonin in plasma and urine are significantly
      but less strongly correlated with levels in CSF.

PMID- 22664307
TI  - Sensitivity of 'mu' rhythm modulation to the relevance of an observed movement
      but not to goal congruency.
AB  - There is some dispute over whether the primary role of a system that processes
      both performed and observed actions (the mirror neuron system) is action
      understanding or the coordination of action with others. We present behavioural
      and EEG data from a motor priming task that shed some light on this debate.
      Participants are asked to make one of two simple actions whilst watching video
      clips of movements that differ in terms of their visuospatial overlap with, and
      goal-related relevance to, the required performed action. The reaction time data
      appear to support a direct matching account where visuospatial overlap is
      prioritised over relevance. However, the EEG data appear to reflect a system that
      is sensitive to the relevance of the observed movement and suggest an action
      prediction role for a mirror neuron system.

PMID- 22664308
TI  - The association of psoriasis with autoimmune diseases.
AB  - BACKGROUND: Previous studies provide evidence that there is a greater frequency
      of autoimmune diseases among patients with psoriasis than in the general
      population. OBJECTIVE: This study examined the association between psoriasis and
      21 common autoimmune diseases, specified a priori. METHODS: A retrospective
      cohort study was conducted among persons who were members of Kaiser Permanente
      Southern California from 2004 to 2011. A total of 25,341 patients with 2 or more
      diagnosis codes for any psoriatic disease were evaluated. Five persons not
      meeting this case definition were matched to each psoriatic patient based on age,
      sex, and length of enrollment. RESULTS: Patients with psoriasis were more likely
      to have at least 1 other autoimmune disease (odds ratio [OR] 1.6; 95% confidence
      interval [CI] 1.5-1.7) and to have at least 2 other autoimmune diseases (1.9; 95%
      CI 1.6-2.4). Of the 17 conditions evaluated, associations with 14 were found to
      be statistically significant. The strongest association was with rheumatoid
      arthritis (3.6; 95% CI 3.4-3.9). LIMITATIONS: Patients with autoimmune conditions
      are likely to have a greater number of health care encounters, which may result
      in overascertainment and misascertainment of immune-mediated conditions, although
      the patients included in the study averaged 5.2 years of observation and the
      comparison subjects were matched on length of enrollment. CONCLUSIONS: The study
      suggests a genetic or environmental cause common across autoimmune diseases.
      Further investigation of individuals with multiple autoimmune diseases may yield
      important clues about the origin and pathogenesis of the disease.

PMID- 22664310
TI  - Somatoform disorder and the DSM-V Workgroup's interim proposals: two central
      issues.
AB  - This paper discusses the published interim report of the DSM-V Workgroup
      onSomatic Symptom Disorders (SSDs). "SSD" is the term proposed by the Workgroup
      to replace "somatoform disorder."

PMID- 22664312
TI  - Actions of "antioxidants" in the protection against atherosclerosis.
AB  - This review addresses the role of oxidative processes in atherosclerosis and its
      resulting cardiovascular disease by focusing on the outcome of antioxidant
      interventions. Although there is unambiguous evidence for the presence of
      heightened oxidative stress and resulting damage in atherosclerosis, it remains
      to be established whether this represents a cause or a consequence of the
      disease. This critical question is complicated further by the increasing
      realization that oxidative processes, including those related to signaling, are
      part of normal cell function. Overall, the results from animal interventions
      suggest that antioxidants provide benefit neither generally nor consistently.
      Where benefit is observed, it appears to be achieved at least in part via
      modulation of biological processes such as increase in nitric oxide
      bioavailability and induction of protective enzymes such as heme oxygenase-1,
      rather than via inhibition of oxidative processes and lipid oxidation in the
      arterial wall. Exceptions to this may be situations of multiple/excessive stress,
      the relevance of which for humans is not clear. This interpretation is consistent
      with the overall disappointing outcome of antioxidant interventions in humans and
      can be rationalized by the spatial compartmentalization of cellular oxidative
      signaling and/or damage, complex roles of oxidant-producing enzymes, and the
      multifactorial nature of atherosclerosis.

PMID- 22664311
TI  - One-year mortality of elderly inpatients with delirium, dementia, or depression
      seen by a consultation-liaison service.
AB  - BACKGROUND: Delirium, dementia and depression are the most prevalent mental
      disorders in elderly patients, and are associated with higher mortality.
      OBJECTIVE: The purpose of this study was to assess 1-year mortality among elderly
      patients with delirium, dementia, or depression seen by a psychiatry consultation
      liaison service in a general hospital. METHODS: We consecutively enrolled
      inpatients 65 years of age and older who were referred for psychiatric
      consultation (n = 614) from 2002 to 2006: 172 were diagnosed with delirium, 92
      with dementia, and 165 with depression. The 1-year mortality rates for the three
      groups of patients were compared by log-rank test. Logistic regression analysis
      was used to identify any possible factors associated with mortality. RESULTS: One
      year mortality was significantly higher in the delirium group than in the
      depression group (p = 0.048), but not significantly different between the
      delirium and dementia groups (p = 0.206), or dementia and depression groups (p =
      0.676). Male patients had a higher mortality rate than female patients in the
      depression group (p = 0.003), but there was no gender difference in the delirium
      and dementia groups. Furthermore, the 1-year mortality of all patients was
      significantly associated with older age (p < 0.001) and length of hospital stay
      (p < 0.001), but not with gender difference and multiple physical comorbidities.
      CONCLUSION: These results suggest that elderly inpatients with delirium seen by a
      psychiatric consultation service have significantly higher mortality than elderly
      inpatients with depression, and that mortality is significantly associated with
      older age and length of hospital stay.

PMID- 22664309
TI  - Obese schizophrenia spectrum patients have significantly higher 10-year general
      cardiovascular risk and vascular ages than obese individuals without severe
      mental illness.
AB  - BACKGROUND: Individuals with schizophrenia have a life expectancy that is 20
      years less than the general population, along with high rates of obesity and
      cardiovascular disease (CVD) mortality. OBJECTIVE: This study assessed the 10
      year general CVD risk and vascular ages of 106 obese schizophrenia spectrum
      patients and 197 demographically matched obese controls without severe mental
      illness (SMI) from the National Health and Nutrition Examination Survey (NHANES).
      METHODS: Vascular age and general CVD risk were calculated using the Framingham
      global CVD calculator, which incorporates age, sex, total and HDL cholesterol
      levels, systolic blood pressure, smoking status, and diabetes or hypertension
      treatment. RESULTS: Obese schizophrenia spectrum patients had a mean vascular age
      that was 14.1 years older than their mean actual age, whereas obese NHANES
      participants had only a 6.7-year difference. The probability of experiencing a
      CVD event within the next 10 years was 10.7% for obese patients and 8.5% for
      obese NHANES participants. CONCLUSION: These findings suggest that schizophrenia
      spectrum patients experience increased metabolic risk independent of weight.
      Primary care clinicians can utilize general CVD risk and vascular age scores to
      communicate metabolic risk more easily and to help make treatment decisions.

PMID- 22664313
TI  - Elucidation of (-)-epicatechin metabolites after ingestion of chocolate by
      healthy humans.
AB  - After absorption in the gastrointestinal tract, (-)-epicatechin is extensively
      transformed into various conjugated metabolites. These metabolites, chemically
      different from the aglycone forms found in foods, are the compounds that reach
      the circulatory system and the target organs. Therefore, it is imperative to
      identify and quantify these circulating metabolites to investigate their roles in
      the biological effects associated with (-)-epicatechin intake. Using authentic
      synthetic standards of (-)-epicatechin sulfates, glucuronides, and O-methyl
      sulfates, a novel LC-MS/MS-MRM analytical methodology to quantify (-)-epicatechin
      metabolites in biological matrices was developed and validated. The optimized
      method was subsequently applied to the analysis of plasma and urine metabolites
      after consumption of dark chocolate, an (-)-epicatechin-rich food, by humans. (-)
      Epicatechin-3'-beta-d-glucuronide (C(max) 290 +/- 49 nM), (-)-epicatechin 3'
      sulfate (C(max) 233 +/- 60 nM), and 3'-O-methyl epicatechin sulfates substituted
      in the 4', 5, and 7 positions were the most relevant (-)-epicatechin metabolites
      in plasma. When plasmatic metabolites were divided into their substituent groups,
      it was revealed that (-)-epicatechin glucuronides, sulfates, and O-methyl
      sulfates represented 33 +/- 4, 28 +/- 5, and 33 +/- 4% of total metabolites
      (AUC(0-24)(h)), respectively, after dark chocolate consumption. Similar
      metabolites were found in urine samples collected over 24h. The total urine
      excretion of (-)-epicatechin was 20 +/- 2% of the amount ingested. In conclusion,
      we describe the entire metabolite profile and its degree of elimination after
      administration of (-)-epicatechin-containing food. These results will help us
      understand more precisely the mechanisms and the main metabolites involved in the
      beneficial physiological effects of flavanols.

PMID- 22664314
TI  - Vitamin E does not prevent bone loss and induced anxiety in rats with ligature
      induced periodontitis.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of vitamin E
      on alveolar bone loss (ABL) and anxiety in rats with ligature-induced
      experimental periodontitis (EP). MATERIAL AND METHODS: Wistar rats were subjected
      to ligature-induced EP and treated with vitamin E (500mg/kg, orally) for 9 days.
      Then anxiety was tested using the elevated plus-maze (EPM) test. All of the
      animals were euthanised by cervical dislocation on day 11. ABL was analysed
      morphometrically and histopathologically. Lipid peroxidation quantification,
      activity of the enzyme superoxide dismutase and immunohistochemistry to tumour
      necrosis factor-alpha (TNF-alpha) and inducible isoform of nitric oxide synthases
      (iNOS) were also tested. RESULTS: EP induced a marked inflammatory process and
      intense ABL. Treatment with vitamin E decreased inflammatory reaction, prevented
      malondialdehyde formation and reduced the immunoreactivity to iNOS, but did not
      decrease ABL. Vitamin E had an anxiogenic effect on rats with or without EP.
      CONCLUSIONS: Vitamin E may have potential to reduce oxidative damage and
      inflammatory response in EP but does not prevent ABL. Attention should be given
      to indiscriminate use of vitamin E due to the risk of causing anxiety in
      patients.

PMID- 22664315
TI  - Cochlear implantation in children with cochlear nerve deficiency: a report of
      nine cases.
AB  - OBJECTIVE: Cochlear implantation for children with cochlear nerve deficiency
      remains controversial, as the presence of the cochlear nerve has been central to
      the success of cochlear implantation. This study sought to investigate whether
      there is any benefit from cochlear implantation for children with cochlear nerve
      deficiency. METHODS: Nine children with cochlear nerve deficiency and bilateral
      prelingual profound sensorineural hearing loss were included in this study. Inner
      ear and internal auditory canal structures were evaluated using magnetic
      resonance imaging and temporal bone computed tomography scans. Meaningful
      auditory integration scales, categories of auditory performance scores, speech
      intelligibility ratings and pure tone average threshold with cochlear
      implantation were measured for evaluation of hearing and speech performance.
      RESULTS: Only four (44.4%) children had a significant improvement in pure tone
      average threshold with the cochlear implant device (77.5 dBHL, 45 dBHL, 51.3 dBHL
      and 68.8 dBHL). No child achieved sufficient speech intelligibility or perception
      ability during a follow-up of at least one year after surgery. CONCLUSIONS: The
      decision to perform cochlear implantation in children with cochlear nerve
      deficiency must be undertaken with caution as it has limited effectiveness and
      uncertain cost-benefit.

PMID- 22664316
TI  - Processing prefixes and suffixes in handwriting production.
AB  - Previous research showed that handwriting production is mediated by
      linguistically oriented processing units such as syllables and graphemes. The
      goal of this study was to investigate whether French adults also activate another
      kind of unit that is more related to semantics than phonology, namely morphemes.
      Experiment 1 revealed that letter duration and inter-letter intervals were longer
      for suffixed words than for pseudo-suffixed words. These results suggest that the
      handwriting production system chunks the letter components of the root and suffix
      into morpheme-sized units. Experiment 2 compared the production of prefixed and
      pseudo-prefixed words. The results did not yield significant differences. This
      asymmetry between suffix and prefix processing has also been observed in other
      linguistic tasks. In suffixed words, the suffix would be processed on-line during
      the production of the root, in an analytic fashion. Prefixed words, in contrast,
      seem to be processed without decomposition, as pseudo-affixed words.

PMID- 22664317
TI  - Children's verbal working memory: relative importance of storage, general
      processing speed, and domain-general controlled attention.
AB  - This study evaluated multiple constraints of verbal working memory in typically
      developing 7- to 11-year-olds. Multiple measures of verbal working memory and the
      predictors-short-term memory storage, general speed, and domain-general
      controlled attention were used. General linear modeling (GLM) showed that storage
      and the efficiency of controlled attention (i.e., speed of updating information
      during attention switching) contributed to significant variance in children's
      verbal working memory. In a secondary analysis verbal storage and domain-general
      attention (focus switching accuracy and speed of updating on switch) emerged as
      significant predictors. Results suggest domain-general attention and verbal
      storage mechanisms to be independent constraints of verbal working memory.

PMID- 22664318
TI  - Aging and performance on an everyday-based visual search task.
AB  - Research on aging and visual search often requires older people to search
      computer screens for target letters or numbers. The aim of this experiment was to
      investigate age-related differences using an everyday-based visual search task in
      a large participant sample (n=261) aged 20-88 years. Our results show that: (1)
      old-old adults have more difficulty with triple conjunction searches with one
      highly distinctive feature compared to young-old and younger adults; (2) age
      related declines in conjunction searches emerge in middle age then progress
      throughout older age; (3) age-related declines are evident in feature searches on
      target absent trials, as older people seem to exhaustively and serially search
      the whole display to determine a target's absence. Together, these findings
      suggest that declines emerge in middle age then progress throughout older age in
      feature integration, guided search, perceptual grouping and/or spreading
      suppression processes. Discussed are implications for enhancing everyday
      functioning throughout adulthood.

PMID- 22664319
TI  - Study of emotional and cognitive impairments in mononeuropathic rats: effect of
      duloxetine and gabapentin.
AB  - Chronic pain is a multidimensional experience that not only includes changes in
      nociception, but also impairments in emotion and cognitive functions. These last
      2 components are not often taken into account in preclinical research. We
      investigated emotional and cognitive impairments in a model of neuropathic pain
      in rats induced by chronic constriction injury (CCI) of the sciatic nerve.
      Nociceptive response, anxiety and depressive-like behaviours as well as cognitive
      capacities were analysed, and the effect of per os administration of duloxetine
      and gabapentin was studied. In the electronic von Frey test, CCI rats exhibited
      mechanical hypersensitivity which can be influenced by duloxetine (3-30 mg/kg)
      and gabapentin (10-30 mg/kg). Cognitive impairments were found in the social but
      not in the spatial (Y-maze) recognition memory tests. Duloxetine and gabapentin
      dose-dependently (3-30 mg/kg) restored social recognition memory impairment.
      Anxiety-like behaviour was only observed in the open-field test (decrease in the
      time spent in the inner zone) but not in the elevated plus maze or in the social
      interactions tests in CCI animals. In this test, impairment in locomotor activity
      (decrease of the total number of crossing) was also observed. Duloxetine and
      gabapentin (10mg/kg) were effective to increase the time spent in the inner zone
      as well as locomotor activity. No difference was observed in depressive-like
      behaviour (saccharin preference test) between sham-operated and CCI rats. These
      data suggest that cognitive rather than emotional impairments seem to be present
      in neuropathic CCI rats and can be reversed by duloxetine and gabapentin.

PMID- 22664320
TI  - Antimicrobial peptide control of pathogenic microorganisms of the oral cavity: a
      review of the literature.
AB  - Antimicrobial peptides, molecules produced in many different organisms, have high
      biocidal activity against several microorganisms. However, several questions
      about these molecules remain unclear. Therefore, this report details a systematic
      survey of the literature on the use of antimicrobial peptides against oral
      pathogens and indicates which peptides and microorganisms are most extensively
      studied. Articles were located using the PubMed and Science Direct databases with
      the following inclusion criteria: publication date between 2002 and 2011;
      keywords "biofilm OR biological film OR biological layer OR bacterial growth" AND
      "peptide" AND "oral cavity OR mouth OR buccal mucosa OR oral mucosa OR mouth
      mucosa"; and abstract in English. A total of 73 articles were selected after
      refinement of the data. An increase in publications focusing on the use of
      antimicrobial peptides against oral microorganisms was observed. In addition, the
      peptides produced by cells of the oral mucosa (defensins, LL-37 and histatins) as
      well as Streptococcus mutans (among cariogenic bacteria) and Porphyromonas
      gingivalis (among periodontal bacteria) were the most studied subjects. It was
      concluded that the use of antimicrobial peptides as a tool for microbial control
      is of increasing importance, likely due to its widespread use, mechanism of
      action, and low rates of bacterial resistance.

PMID- 22664321
TI  - Gonadotropin-inhibitory hormone (GnIH) and its receptor in the female pig: cDNA
      cloning, expression in tissues and expression pattern in the reproductive axis
      during the estrous cycle.
AB  - Since its discovery, gonadotropin-inhibitory hormone (GnIH) has appeared to act
      as a key neuropeptide in the control of vertebrate reproduction. GnIH acts via
      the novel G protein-coupled receptor 147 (GPR147) to inhibit gonadotropin release
      and synthesis. To determine the physiological functions of GnIH in the pig, a
      study was conducted to clone and sequence the cDNA of the GnIH precursor and
      GPR147. Our results demonstrated that the cloned pig GnIH precursor cDNA encoded
      three LPXRF and that its receptor possessed typical transmembrane features.
      Subsequently, tissue expression studies revealed that GnIH was mainly expressed
      in the brain, corresponding largely with the tissue expression patterns of GPR147
      in the pig. The expression patterns in the reproductive axis of the female pig
      across the estrous cycle were also systemically investigated. The hypothalamic
      levels of both GnIH and its receptor mRNA were lowest in estrus and peaked in the
      proestrus and diestrus phases. The highest pituitary GnIH mRNA level was detected
      in the metestrus, and its receptor displayed a somewhat similar pattern of
      expression to that of the ligand. However, the expression patterns of GnIH and
      GPR147 were negatively correlated in the ovary. Immunolocalization in the ovary
      during the estrous cycle revealed that the immunoreactivities of GnIH and GPR147
      were mainly localized in the granulosa and theca cells of the antral follicles
      during proestrus and estrus and in the luteal cells during metestrus and
      diestrus. Taken together, this research provided molecular and morphological data
      for further study of GnIH in the pig.

PMID- 22664322
TI  - Galanin and its receptors: a novel strategy for appetite control and obesity
      therapy.
AB  - The rapid increase in the prevalence of overweight and obesity is becoming an
      important health problem. Overweight and obesity may cause several metabolic
      complications, including type 2 diabetes mellitus, hyperlipidemia, high
      cholesterol, coronary artery disease as well as hypertension. Prevention and
      treatment of obesity will benefit the treatment of these related diseases.
      Current strategies for treatment of obesity are not adequately effective and are
      frequently companied with many side effects. Thus, new ways to treat obesity are
      urgently needed. Galanin is undoubtedly involved in the regulation of food intake
      and body weight. The aim of this review is to provide up-to-date knowledge
      concerning the roles of central and peripheral galanin as well as its receptors
      in the regulation of metabolism, obesity and appetite. We also highlight the
      mechanisms of galanin and its receptors in experimental obesity, trying to
      establish a novel anti-obesity strategy.

PMID- 22664323
TI  - Inside out: a neuro-behavioral signature of free recall dynamics.
AB  - Free recall (FR) is a ubiquitous internally-driven retrieval operation that
      crucially affects our day-to-day life. The neural correlates of FR, however, are
      not sufficiently understood, partly due to the methodological challenges
      presented by its emerging property and endogenic nature. Using fMRI and
      performance measures, the neuro-behavioral correlates of FR were studied in 33
      healthy participants who repeatedly encoded and retrieved word-lists. Retrieval
      was determined either overtly via verbal output (Experiment 1) or covertly via
      motor responses (Experiment 2). Brain activation during FR was characterized by
      two types of performance-based parametric analyses of retrieval changes over
      time. First was the elongation in inter response time (IRT) assumed to represent
      the prolongation of memory search over time, as increased effort was needed.
      Using a derivative of this parameter in whole brain analysis revealed the default
      mode network (DMN): longer IRT within FR blocks correlated with less deactivation
      of the DMN, representing its greater recruitment. Second was the increased number
      of words retrieved in repeated encoding-recall cycles, assumed to represent the
      learning process. Using this parameter in whole brain analysis revealed increased
      deactivation in the DMN (i.e., less recruitment). Together our results
      demonstrate the naturally occurring dynamics in the recruitment of the DMN during
      utilization of internally generated processes during FR. The contrasting effects
      of increased and decreased recruitment of the DMN following dynamics in memory
      search and learning, respectively, supports the idea that with learning FR is
      less dependent on neural operations of internally-generated processes such as
      those initially needed for memory search.

PMID- 22664325
TI  - Tumor necrosis factor-alpha enhanced fusions between oral squamous cell carcinoma
      cells and endothelial cells via VCAM-1/VLA-4 pathway.
AB  - Fusion between cancer cells and host cells, including endothelial cells, may
      strongly modulate the biological behavior of tumors. However, no one is sure
      about the driving factors and underlying mechanism involved in such fusion. We
      hypothesized in this study that inflammation, one of the main characteristics in
      tumor microenvironment, serves as a prominent catalyst for fusion events. Our
      results showed that oral cancer cells can fuse spontaneously with endothelial
      cells in co-culture and inflammatory cytokine tumor necrosis factor-alpha (TNF
      alpha) increased fusion of human umbilical vein endothelium cells and oral cancer
      cells by up to 3-fold in vitro. Additionally, human oral squamous cell carcinoma
      cell lines and 35 out of 50 (70%) oral squamous carcinoma specimens express VLA
      4, an integrin, previously implicated in fusions between human peripheral blood
      CD34-positive cells and murine cardiomyocytes. Expression of VCAM-1, a ligand for
      VLA-4, was evident on vascular endothelium of oral squamous cell carcinoma.
      Moreover, immunocytochemistry and flow cytometry analysis revealed that
      expression of VCAM-1 increased obviously in TNF-alpha-stimulated endothelial
      cells. Anti-VLA-4 or anti-VCAM-1 treatment can decrease significantly cancer
      endothelial adhesion and block such fusion. Collectively, our results suggested
      that TNF-alpha could enhance cancer-endothelial cell adhesion and fusion through
      VCAM-1/VLA-4 pathway. This study provides insights into regulatory mechanism of
      cancer-endothelial cell fusion, and has important implications for the
      development of novel therapeutic strategies for prevention of metastasis.

PMID- 22664327
TI  - Mitochondrial anti-viral immunity.
AB  - In the cytosol, the sensing of RNA viruses by the RIG-I-like receptors (RLRs)
      triggers a complex signaling cascade where the mitochondrial antiviral signaling
      protein (MAVS) plays a crucial role in orchestrating the innate host response
      through the induction of antiviral and inflammatory responses. Hence, in addition
      to their known roles in the metabolic processes and the control of programmed
      cell death, mitochondria are now emerging as a fundamental hub for innate anti
      viral immunity. This review summarizes the findings related to the MAVS adapter
      and mitochondria in the innate immune response to RNA viruses.

PMID- 22664326
TI  - Reactive oxygen species stimulates epithelial mesenchymal transition in normal
      human epidermal keratinocytes via TGF-beta secretion.
AB  - Epithelial to mesenchymal transition (EMT) plays an important role in tumor
      progression, and is an early step in carcinogenesis. Although reactive oxygen
      species (ROS) are known to be implicated in EMT in many tumor cell types, its
      exact role in EMT initiation in normal human cells, especially epidermal
      keratinocytes (NHEKs), remains unknown. To clarify whether ROS induce EMT in
      NHEKs, and to establish how ROS regulate EMT, we examined the effect of hydrogen
      peroxide (H(2)O(2)) on the expression of molecules involved in EMT and cell
      morphology in NHEKs. H(2)O(2) altered the expression of EMT biomarkers, including
      downregulation of epithelial cadherin and upregulation of alpha-smooth muscle
      actin, through a transcriptional modulator, Snail1. H(2)O(2) also induced
      epithelial to fibroblast-like morphological changes, together with upregulation
      of EMT biomarkers, and promoted phosphorylation of ERK1/2 and JNK in a time
      dependent manner. Interestingly, H(2)O(2) stimulated the expression and secretion
      of TGF-beta1 in NHEKs. Exogenous TGF-beta1 also induced the expression of EMT
      biomarkers. In contrast, neutralizing antibody anti-TGF-beta1 antibody or
      inhibitor of TGF-beta receptor type I suppressed the expression of EMT
      biomarkers. Our results suggest that ROS stimulated TGF-beta1 secretion and MAPK
      activation, resulting in EMT initiation in NHEKs.

PMID- 22664328
TI  - Complex I impairment in mitochondrial diseases and cancer: parallel roads leading
      to different outcomes.
AB  - Respiratory chain complex I (CI) dysfunctions have been recognized as one of the
      most frequent causes of mitochondrial neuro-muscular disorders. Moreover, latest
      reports reveal that CI impairment is a major contributing factor in many other
      pathological processes, including cancer. In fact, energy depletion, oxidative
      stress and metabolites unbalance are frequently associated with CI functional and
      structural alterations. The occurrence of mitochondrial DNA (mtDNA) mutations is
      a shared feature in neuro-muscular diseases and cancer; however, the two
      diverging phenotypes arise depending on the mutation type (disassembling versus
      non-disassembling mutations), the mutant load and the cytotype. In this review,
      we unify our knowledge on CI impairment caused by mutations in structural CI
      genes and assembly chaperones, both in mitochondrial disorders and cancer,
      stratifying such mutations based on their functional versus structural effects.
      We summarize shared and specific metabolic consequences of CI dysfunction in
      these pathologies, which allow us to draw two parallel roads that lead to
      different clinical outcomes. This article is part of a Directed Issue entitled:
      Bioenergetic dysfunction, adaptation and therapy.

PMID- 22664324
TI  - Accent processing in dementia.
AB  - Accented speech conveys important nonverbal information about the speaker as well
      as presenting the brain with the problem of decoding a non-canonical auditory
      signal. The processing of non-native accents has seldom been studied in
      neurodegenerative disease and its brain basis remains poorly understood. Here we
      investigated the processing of non-native international and regional accents of
      English in cohorts of patients with Alzheimer's disease (AD; n=20) and
      progressive nonfluent aphasia (PNFA; n=6) in relation to healthy older control
      subjects (n=35). A novel battery was designed to assess accent comprehension and
      recognition and all subjects had a general neuropsychological assessment.
      Neuroanatomical associations of accent processing performance were assessed using
      voxel-based morphometry on MR brain images within the larger AD group. Compared
      with healthy controls, both the AD and PNFA groups showed deficits of non-native
      accent recognition and the PNFA group showed reduced comprehension of words
      spoken in international accents compared with a Southern English accent. At
      individual subject level deficits were observed more consistently in the PNFA
      group, and the disease groups showed different patterns of accent comprehension
      impairment (generally more marked for sentences in AD and for single words in
      PNFA). Within the AD group, grey matter associations of accent comprehension and
      recognition were identified in the anterior superior temporal lobe. The findings
      suggest that accent processing deficits may constitute signatures of
      neurodegenerative disease with potentially broader implications for understanding
      how these diseases affect vocal communication under challenging listening
      conditions.

PMID- 22664329
TI  - ATP synthase oligomerization: from the enzyme models to the mitochondrial
      morphology.
AB  - Mitochondrial F(1)F(o) ATP synthase is an enzymatic complex involved in the
      aerobic synthesis of ATP. It is well known that several enzymes are organized in
      supramolecular complexes in the inner mitochondrial membrane. The ATP synthase
      supramolecular assembly is mediated through two interfaces. One leads to dimer
      formation and the other to oligomer formation. In yeast, the presence of ATP
      synthase oligomers has been described as essential to the maintenance of the
      mitochondrial cristae ultrastructure. Indeed, the destabilization of the
      interactions between monomers was shown to alter the organization of the inner
      mitochondrial membrane, leading to the formation of onion-like structures similar
      to those observed in some mitochondrial pathologies. By using information
      obtained this decade (structure modeling, electron microscopy and cross-linking),
      this paper (i) reviews the actual state of the art and (ii) proposes a
      topological model of the transmembrane domains and interfaces of the ATP
      synthase's tetramer. This review also discusses the physiological role of this
      oligomerization process and its potential implications in mammal pathology. This
      article is part of a Directed Issue entitled: Bioenergetic Dysfunction,
      adaptation and therapy.

PMID- 22664330
TI  - Availability, not respiratory capacity governs oxygen consumption of solid
      tumors.
AB  - Contrary to conventional belief, the mitochondria of most cancer cells usually
      function normally, i.e., their respiratory capacity is not fundamentally impaired
      as compared to normal cells. Strong evidence against the misconception of
      mitochondrial dysfunction is provided by in vivo data clearly showing that O(2)
      availability is the major determinant of the O(2) consumption rate of cancer
      cells, independent of the means for increasing availability (e.g., by increasing
      blood flow or by elevating arterial O(2) content, the latter being accomplished
      either by an increase in the hemoglobin level and/or arterial hyperoxia).
      Additional support against the Warburg effect in its original concept comes from
      normal temperature coefficients (Q(10)) for O(2) consumption rates of malignant
      cells. Thus, the Warburg hypothesis postulating that mitochondrial dysfunction in
      cancer cells forces them to generate energy with a poor ATP yield through
      glycolysis appears to be elusive. Instead, due to a "reprogrammed" cancer cell
      metabolism, glycolysis is used to produce intermediates as building blocks for
      various biosynthetic pathways of cancer cells.

PMID- 22664331
TI  - DJ-1 protein protects dopaminergic neurons against 6-OHDA/MG-132-induced
      neurotoxicity in rats.
AB  - Parkinson disease (PD) is the second most common neurodegenerative disease, and
      it cannot be completely cured by current medications. In this study, DJ-1 protein
      was administrated into medial forebrain bundle of PD model rats those had been
      microinjected with 6-hydroxydopamine (6-OHDA) or MG-132. We found that DJ-1
      protein could reduce apomorphine-induced rotations, inhibit reduction of dopamine
      contents and tyrosine hydroxylase levels in the striatum, and decrease
      dopaminergic neuron death in the substantia nigra. In 6-OHDA lesioned rats,
      uncoupling protein-4, uncoupling protein-5 and superoxide dismutase-2 (SOD2) mRNA
      and SOD2 protein were increased when DJ-1 protein was co-injected.
      Simultaneously, administration of DJ-1 protein reduced alpha-synuclein and
      hypoxia-inducible factor 1alpha mRNA and alpha-synuclein protein in MG-132
      lesioned rats. Therefore, DJ-1 protein protected dopaminergic neurons in two PD
      model rats by increasing antioxidant capacity and inhibiting alpha-synuclein
      expression.

PMID- 22664332
TI  - Effect of copper and disulfiram combination therapy on the macular mouse, a model
      of Menkes disease.
AB  - Menkes disease (MD) is a genetic neurodegenerative disorder characterized by
      copper deficiency due to a defect in ATP7A. Standard treatment involves
      parenteral copper-histidine administration. However, the treatment is ineffective
      if initiated after two months of age, because the administered copper accumulates
      in the blood-brain barrier and is not transported to neurons. To resolve this
      issue, we investigated the effects of a combination therapy comprising copper and
      disulfiram, a lipophilic chelator, in the macular mouse, an animal model of MD.
      Seven-day-old macular mice treated subcutaneously with 50 MUg of CuCl(2) on
      postnatal day 4 were used. The mice were given a subcutaneous injection of
      CuCl(2) (10 MUg) with oral administration of disulfiram (0.3mg/g body weight)
      twice a week until eight weeks of age, and then sacrificed. Copper concentrations
      in the cerebellum, liver, and serum of treated macular mice were significantly
      higher than those of control macular mice, which received only copper. Mice
      treated with the combination therapy exhibited higher cytochrome c oxidase
      activity in the brain. The ratios of noradrenaline and adrenaline to dopamine in
      the brain were also increased by the treatment, suggesting that dopamine beta
      hydroxylase activity was improved by the combination therapy. Liver and renal
      functions were almost normal, although renal copper concentration was higher in
      treated macular mice than in controls. These results suggest that disulfiram
      facilitates the passage of copper across the blood-brain barrier and that copper
      disulfiram combination therapy may be an effective treatment for MD patients.

PMID- 22664333
TI  - Discovery of human zinc deficiency: 50 years later.
AB  - Essentiality of zinc for humans and its deficiency was recognized in 1963. During
      the past 50 years, it has become apparent that deficiency of zinc in humans is
      prevalent. Nutritional deficiency of zinc may affect nearly 2 billion subjects in
      the developing world. Consumption of cereal proteins high in phytate decreases
      the availability of zinc for absorption. Conditioned deficiency of zinc is also
      very common. Growth retardation, hypogonadism in males, rough skin, impaired
      immunity, neuro-sensory disorder and cognitive impairment are some of the
      clinical manifestations of zinc deficiency. Zinc is involved in many biochemical
      functions. Over 300 enzymes require zinc for their activation and nearly 2000
      transcription factors require zinc for gene expression. Zinc is essential for
      cell mediated immunity. Zinc is also an effective antioxidant and anti
      inflammatory agent. In therapeutic dosages, zinc has been used for the treatment
      of acute diarrhea in infants and children, common cold, Wilson's disease, sickle
      cell disease and for prevention of blindness in patients with age related macular
      degeneration.

PMID- 22664334
TI  - Involvement of neuroleptic drugs in selenium deficiency and sudden death of
      cardiac origin: study and human post-mortem examination.
AB  - The involvement of psychotropic drugs in sudden deaths has been highlighted. The
      objective of this work was to establish a link between selenium levels in heart
      tissue, psychotropic treatment and sudden death. Selenium levels were measured by
      electrothermal atomic absorption spectroscopy post-mortem in heart, brain and
      liver. Histological examination evidenced dilated cardiomyopathy in 45% of cases,
      left ventricular hypertrophy in 36%, and ischemic coronaropathy in 18%. A
      significant reduction of myocardial selenium levels compared to controls was seen
      in patients treated with neuroleptic drugs or meprobamate. No changes in brain or
      liver selenium levels were seen. These results suggest that selenium deficiency
      can facilitate sudden death in patients on psychotropic drugs. The reduced
      activity of glutathione peroxidase due to selenium deficiency can result in
      augmented oxidative stress in myocardial cells and myocardiopathy leading to
      sudden death.

PMID- 22664335
TI  - Selenium and cancer prevention: observations and complexity.
AB  - Early case-control and intervention studies suggested that selenium (Se) species
      might reduce the risk of cancer and in a pre-diagnostic case-control study from
      1986 [1] we found that the higher the serum Se concentration, the lower was the
      odds ratio of thyroid cancer. Our data showed, however, that this observation
      occurred late in the pre-diagnostic period indicating that low serum Se was
      simply a consequence of thyroid cancer. In 1986 we therefore concluded that the
      only way to get an indisputable and lasting answer to the question was to carry
      out properly designed intervention studies. Great was our frustration therefore
      when we in 2003 [2] discovered that thyroid cancer morbidity is a fractal
      variable powered by such complexity that we may never find a definite and
      enduring answer: Even the best, randomised, controlled trial comparing the
      incidence rate among exposed and controls can only produce temporary answers due
      to the complexity background. The only possible way to come up with a lasting
      solution seems to be by means of reductionist experiments, but they have to be
      tested on man and then one is back to square one.

PMID- 22664336
TI  - Integrated strategies needed to prevent iron deficiency and to promote early
      child development.
AB  - Iron deficiency (ID) and iron deficiency anemia (IDA) are global public health
      problems that differentially impact pregnant women and infants in low and middle
      income countries. IDA during the first 1000 days of life (prenatally through 24
      months) has been associated with long term deficits in children's socio
      emotional, motor, cognitive, and physiological functioning. Mechanisms linking
      iron deficiency to children's development may include alterations to dopamine
      metabolism, myelination, and hippocampal structure and function, as well as
      maternal depression and unresponsive caregiving, potentially associated with
      maternal ID. Iron supplementation trials have had mixed success in promoting
      children's development. Evidence suggests that the most effective interventions
      to prevent iron deficiency and to promote early child development begin early in
      life and integrate strategies to ensure adequate iron and nutritional status,
      along with strategies to promote responsive mother-child interactions and early
      learning opportunities.

PMID- 22664338
TI  - Kidney cancer.

PMID- 22664337
TI  - Olfactory functions at the intersection between environmental exposure to
      manganese and Parkinsonism.
AB  - The olfactory function can be affected by occupational and environmental exposure
      to various neurotoxicants that can be transported through the olfactory pathway.
      Olfactory impairment is a highly recurrent non-motor dysfunction in Parkinson's
      disease and is considered an early predictive sign of neurodegeneration. Changes
      in olfactory perception may be caused by a dopaminergic dysregulation, possibly
      related to changes at the level of dopamine receptors. Manganese is an essential
      element that can become neurotoxic in various conditions inducing an overload in
      the organism. Being actively transported through the olfactory tract, manganese
      can cause impairment of olfactory function and motor coordination in different
      age groups like children and elderly. Odor and motor changes are interrelated and
      may be caused by a Mn-induced dopaminergic dysregulation affecting both
      functions. Given these findings, further research is imperative on the possible
      role of manganese exposure as a pathogenetic factor for Parkinsonism.

PMID- 22664339
TI  - The effect of repeated, four-weekly eprinomectin treatment on milk production in
      pasture-based, seasonally-calving dairy cattle.
AB  - A randomised clinical trial from the North Island of New Zealand was conducted to
      assess the effect of repeated anthelmintic treatment on milk production, and to
      assess factors that affect treatment response. Nine hundred and twenty three
      multiparous, lactating dairy cattle from three pasture-based, spring-calving
      dairy herds were enrolled in this trial. Within each herd, cattle were stratified
      on age and calving date, and were randomly allocated to treatment (n=319) or
      control (n=604) groups. The treatment group received >= 0.05 mg/kg of topical
      eprinomectin every 28 days for eight treatments during lactation. Pooled-milk
      from treated cows and bulk-milk samples were obtained at each treatment and
      analysed with an Ostertagia antibody ELISA, expressed as optical density ratios
      (ODR). Bi-monthly milk data were collected and expressed as energy-corrected milk
      (kg/day; ECM). A linear mixed model was used to analyse ECM, with cow as the
      random effect. The effect of anthelmintic treatment on days from calving, and
      start-of-mating, to conception were analysed with Cox-proportional hazard models.
      ODR values ranged from 0.6 to 1.3; there were no differences in ODR between herds
      (p=0.12), or between pooled-milk from treated cows and bulk-milk (p=0.26).
      Repeated treatments had no effect on daily ECM yields (p=0.74). However, there
      was a significant treatment * herd interaction (p=0.03); treatment increased ECM
      in one herd by 0.781 kg/cow/day (p=0.015), but resulted in a non-significant
      decrease in the other two herds. A curvilinear interaction existed between days
      in-milk and treatment response (p=0.039); the greatest treatment effect occurred
      during mid-lactation. Previous year milk production (p=0.46) and age (p=0.11) did
      not influence the effect of treatment on ECM. Treatment had no effect on any
      reproductive parameter. In conclusion, under New Zealand pastoral conditions,
      anthelmintic treatment increased milk production in one herd, but had no effect
      in two other herds. Further work is needed to identify why this variation in
      gastro-intestinal parasitism occurs.

PMID- 22664340
TI  - Exploration of the epidemiological consequences of resistance to gastro
      intestinal parasitism and grazing management of sheep through a mathematical
      model.
AB  - Predicting the impacts of selection for decreased faecal egg count (FEC) (i.e.
      host resistance) in grazing ruminants is difficult, due to complex interactions
      between parasite epidemiology, management and host responses. A mathematical
      model including heritable between lamb variation in host-parasite interactions,
      Teladorsagia circumcincta epidemiology and anthelmintic drenching, was developed
      and used to (i) address such interactions and their impact on outcomes including
      FEC, live weight (LW, kg) and pasture larval contamination (PC, larvae/kg DM),
      and (ii) investigate how grazing management strategies, aimed at reducing host
      exposure to infective larvae via pasture moves at 40 day intervals, affect these
      outcomes. A population of 10,000 lambs was simulated and resultant FEC
      predictions used to assign the 1,000 lambs with the highest and lowest predicted
      FEC to 'susceptible' (S) and 'resistant', (R) groups, respectively. The predicted
      average FEC of the S group was ~8.5-fold higher than the R group across a grazing
      season. The R and S groups were then simulated to graze separate pastures (R(sep)
      and S(sep)); and repeated for 3 grazing seasons to allow predictions to diverge
      and stabilize. Further, different grazing strategies were superimposed on all
      groups. PC and average FEC were affected by whether lambs of different resistance
      genotype grazed together or separately, with differences increasing across
      grazing seasons. By the third grazing season the average PC of the R(sep) group
      was reduced by ~83%, and the S(sep) group was increased by ~240%, in comparison
      to the whole population average. Average FEC of the R(sep) group was reduced by
      ~40%, and the S(sep) group increased by ~46% in comparison to the R and S groups,
      respectively, whilst drenching had little impact on the proportional differences
      in FEC between groups. Predicted LW was similar for the R and R(sep) groups
      irrespective of anthelmintic treatment, whilst LW of the S(sep) group was reduced
      by ~14% compared to the S group for un-drenched lambs, and by ~4% for drenched
      lambs. The differing grazing strategies were predicted to have little impact on
      FEC or LW, with the exception of the S(sep) group which was predicted to have a 2
      kg increase in LW when drenched and moved to a clean pasture. Together, these
      results suggest that host genotype has a substantial impact on parasite
      epidemiology, however the benefits of anthelmintic treatment and grazing
      management should only be expected for susceptible animals. This supports the use
      of targeted selective treatment, focussing on susceptible animals.

PMID- 22664342
TI  - NSAIDs: eNdocannabinoid stimulating anti-inflammatory drugs?
AB  - Read any pharmacology textbook and the message is clear: nonsteroidal anti
      inflammatory drugs (NSAIDs) act by inhibiting the activity of cyclooxygenase
      (COX) and thereby the production of prostaglandins. However, evidence is
      accumulating that NSAIDs involve the endocannabinoid system in their actions, and
      that such effects may pave the way towards the design of new analgesics that are
      not plagued with the gastrointestinal and cardiovascular adverse actions that are
      associated with this class of drugs. In this Opinion article, our current
      understanding of the involvement of the endocannabinoid system in the actions of
      NSAIDs is described, and the ways in which this can lead to novel drug
      development is discussed.

PMID- 22664344
TI  - Sphingomyelinase C from Streptomyces sp. A9107: unusual primary structure for
      bacterial sphingomyelinase C.
AB  - A sphingomyelinase C (SMase) was identified in the culture supernatant of
      Streptomyces sp. A9107 (S-SMase). Although S-SMase seems to be a typical
      bacterial SMase, the primary structure of S-SMase was unusual for known bacterial
      SMase. The gene was functionally overexpressed in the culture medium of
      recombinant Rhodococcus erythropolis.

PMID- 22664343
TI  - Involvement of glutamate 97 in ion influx through photo-activated
      channelrhodopsin-2.
AB  - The light absorption of a channelrhodopsin-2 (ChR2) is followed by conformational
      changes to the molecule, which allows the channel structure to become permeable
      to cations. Previously, a single point mutation in ChR2, which replaces glutamate
      residue 97 with a nonpolar alanine (E97A), was found to attenuate the
      photocurrent, suggesting that the E97 residue is involved in ion flux regulation.
      Here, the significance of E97 and its counterpart ChR1 (E136) were extensively
      studied by mutagenesis, whereby we replaced these glutamates with aspartate (D),
      glutamine (Q) or arginine (R). We found that the charge at this position strongly
      influences ion permeation and that the photocurrents were attenuated in the order
      of ChR2>E97D~E97Q>E97R. We observed similar results with our
      chimeric/synthetic/artificial construct, ChR-wide receiver (ChRWR), which
      contains the first to fifth transmembrane helices of ChR1. The E-to-Q or E-to-R
      mutations, but not the E-to-D mutation, strongly retarded the sensitivity to the
      Gd(3+)-dependent blocking of the ChR1 or ChR2 channels. Our results suggest that
      the glutamate residue at this position lies in the outer pore, where it interacts
      with a cation to facilitate dehydration, and that this residue is the primary
      binding target of Gd(3+).

PMID- 22664341
TI  - Synthetic biology with surgical precision: targeted reengineering of signaling
      proteins.
AB  - The complexity of living systems exceeds everything else studied by natural
      sciences. Sophisticated networks of intimately intertwined signaling pathways
      coordinate cellular functions. Clear understanding how the integration of
      multiple inputs produces coherent behavior is one of the major challenges of cell
      biology. Integration via perfectly timed highly regulated protein-protein
      interactions and precise targeting of the "output" proteins to particular
      substrates is emerging as a common theme of signaling regulation. This often
      involves specialized scaffolding proteins, whose key function is to ensure that
      correct partners come together in an appropriate place at the right time.
      Defective or faulty signaling underlies many congenital and acquired human
      disorders. Several pioneering studies showed that ectopic expression of existing
      proteins or their elements can restore functions destroyed by mutations or
      normalize the signaling pushed out of balance by disease and/or current small
      molecule-based therapy. Several recent studies show that proteins with new
      functional modalities can be generated by mixing and matching existing domains,
      or via functional recalibration and fine-tuning of existing proteins by precisely
      targeted mutations. Using arrestins as an example, we describe how manipulation
      of individual functions yields signaling-biased proteins. Creative protein
      redesign generates novel tools valuable for unraveling the intricacies of cell
      biology. Engineered proteins with specific functional changes also have huge
      therapeutic potential in disorders associated with inherited or acquired
      signaling errors.

PMID- 22664345
TI  - Bovine milk phospholipid fraction protects Neuro2a cells from endoplasmic
      reticulum stress via PKC activation and autophagy.
AB  - Endoplasmic reticulum stress commonly causes neuronal damage in a lot of
      neurodegenerative diseases. In this study, we examined neuroprotective effect of
      bovine milk phospholipid fraction (mPL) on mouse neuroblastoma Neuro2a cells from
      endoplasmic reticulum (ER) stress induced cell death. Neuro2a cells were induced
      cell death by ER stressor tunicamycin (TM) or thapsigargin (TG), and studied
      whether mPL could attenuate the toxicity. By preincubation with mPL, the cell
      viabilities were significantly increased in TM or TG treated cells, and caspase
      12 activated cells induced by TM or TG treatment were significantly decreased.
      Protein kinase C inhibitor GF109203x significantly reduced the protective effect
      on TM induced cell death, and autophagy inhibitor 3-methyladenine reduced the
      protective effect on TM or TG induced cell death. Moreover, preincubation with
      mPL significantly stimulated autophagosomes formation observed by
      dansylcadaverine staining. Our data suggest that mPL will be applicable to
      prevent neurodegenerative diseases caused by ER stress.

PMID- 22664346
TI  - Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf) in male, pregnant
      and non-pregnant female rabbits after single high dose inhalation exposure.
AB  - 2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a novel refrigerant intended for use
      in mobile air conditioning. It showed a low potential for toxicity in rodents
      studies with most NOAELs well above 10,000 ppm in guideline compliant toxicity
      studies. However, a developmental toxicity study in rabbits showed mortality at
      exposure levels of 5,500 ppm and above. No lethality was observed at exposure
      levels of 2,500 and 4,000 ppm. Nevertheless, increased subacute inflammatory
      heart lesions were observed in rabbits at all exposure levels. Since the
      lethality in pregnant animals may be due to altered biotransformation of HFO
      1234yf and to evaluate the potential risk to pregnant women facing a car crash,
      this study compared the acute toxicity and biotransformation of HFO-1234yf in
      male, female and pregnant female rabbits. Animals were exposed to 50,000 ppm and
      100,000 ppm for 1h. For metabolite identification by (19)F NMR and LC/MS-MS,
      urine was collected for 48 h after inhalation exposure. In all samples, the
      predominant metabolites were S-(3,3,3-trifluoro-2-hydroxypropanyl)-mercaptolactic
      acid and N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine. Since no
      major differences in urinary metabolite pattern were observed between the groups,
      only N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine excretion was
      quantified. No significant differences in recovery between non-pregnant (43.10 +/
      22.35 MUmol) and pregnant female (50.47 +/- 19.72 MUmol) rabbits were observed,
      male rabbits exposed to 100,000 ppm for one hour excreted 86.40 +/- 38.87 MUmol.
      Lethality and clinical signs of toxicity were not observed in any group. The
      results suggest that the lethality of HFO-1234yf in pregnant rabbits unlikely is
      due to changes in biotransformation patterns or capacity in pregnant rabbits.

PMID- 22664347
TI  - Non-coplanar polychlorinated biphenyls (PCBs) are direct agonists for the human
      pregnane-X receptor and constitutive androstane receptor, and activate target
      gene expression in a tissue-specific manner.
AB  - The polychlorinated biphenyl group possesses high environmental persistence,
      leading to bioaccumulation and a number of adverse effects in mammals. Whilst
      coplanar PCBs elicit their toxic effects through agonism of the aryl hydrocarbon
      receptor; however, non-coplanar PCBs are not ligands for AhR, but may be ligands
      for members of the nuclear receptor family of proteins. To better understand the
      biological actions of non-coplanar PCBs, we have undertaken a systematic analysis
      of their ability to activate PXR and CAR-mediated effects. Cells were exposed to
      a range of non-coplanar PCBs (99, 138, 153, 180 and 194), or the coplanar PCB77:
      Direct activation of PXR and CAR was measured using a mammalian receptor
      activation assay in human liver cells, with rifampicin and CITCO used as positive
      controls ligands for PXR and CAR, respectively; activation of target gene
      expression was examined using reporter gene plasmids for CYP3A4 and MDR1
      transfected into liver, intestine and lung cell lines. Several of the non
      coplanar PCBs directly activated PXR and CAR, whilst the coplanar PCB77 did not.
      Non-coplanar PCBs were also able to activate PXR/CAR target gene expression in a
      substitution- and tissue-specific manner. Non-coplanar PCBs act as direct
      activators for the nuclear receptors PXR and CAR, and are able to elicit
      transcriptional activation of target genes in a substitution- and tissue
      dependent manner. Chronic activation of PXR/CAR is linked to adverse effects and
      must be included in any risk assessment of PCBs.

PMID- 22664348
TI  - Mechanisms and regulation of autophagosome formation.
AB  - Autophagy is an intracellular pathway for the bulk degradation of cytoplasmic
      substances such as cytosol, protein aggregates and organelles. Autophagy is
      characterized by the formation of double-membrane bound vesicles called
      autophagosomes, which engulf the cargo and transport it to the vacuole/lysosome
      for breakdown and recycling. Even though several proteins in this pathway have
      been identified, little is known about the mechanism of action of these proteins
      during autophagosome biogenesis. In this review we briefly discuss recent
      findings on the molecular players and mechanisms involved in autophagosome
      formation. In particular, we will focus on the mechanisms regulating membrane
      recruitment as well as membrane remodeling during autophagosome formation.

PMID- 22664349
TI  - Lipopolysaccharide administration in the dominant mouse destabilizes social
      hierarchy.
AB  - Sickness behavior is a set of behavioral changes that are part of an adaptive
      strategy to overcome infection. Mice that interact with conspecifics displaying
      sickness behavior also show relevant behavioral changes. In this work we sought
      to determine the role of sickness behavior display by a dominant mouse as a
      promoter of hierarchy instability. We treated the dominant mouse within a dyad
      with lipopolysaccharide (LPS) (400 MUg/kg, i.p.) for three consecutive days and
      assessed social dominance behavior. Since elder animals display increased
      inflammatory responses and the behaviors toward conspecifics are influenced by
      kinship we also assessed whether kinship and age, might influence sickness
      related hierarchy instability. Our results show that administration of LPS in the
      dominant mouse promotes social instability within a dyad, and indicates that this
      instability could be influenced by kinship and age.

PMID- 22664350
TI  - WITHDRAWN: Enabling infrastructure for global health product development.
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- 22664351
TI  - [Pneumocystis jiroveci pneumonia in a Crohn's disease patient treated with
      adalimumab].

PMID- 22664352
TI  - Molecular characterizations of Cryptosporidium, Giardia, and Enterocytozoon in
      humans in Kaduna State, Nigeria.
AB  - The use of molecular diagnostic tools in epidemiological investigations of
      Cryptosporidium, Giardia, and Enterocytozoon has provided new insights into their
      diversity and transmission pathways. In this study, 157 stool specimens from 2
      month to 70-year-old patients were collected, a polymerase chain reaction (PCR)
      restriction fragment length polymorphism (RFLP) analysis of the small subunit
      (SSU) rRNA gene was used to detect and differentiate Cryptosporidium species, and
      DNA sequence analysis of the 60 kDa glycoprotein (gp60) gene was used to subtype
      Cryptosporidium hominis and Cryptosporidium parvum. Giardia duodenalis, and
      Enterocytozoon bieneusi in the specimens were detected using PCR and sequence
      analysis of the triosephosphate isomerase (tpi) gene and internal transcribed
      spacer (ITS), respectively. C. hominis and C. parvum were found in two (1.3%) and
      one (0.6%) specimen respectively, comprising of Ia and IIe (with 8 nucleotide
      substitutions) subtype families. The G. duodenalis A2 subtype was detected in
      five (3.2%) specimens, while four genotypes of E. bieneusi, namely A, type IV, D
      and WL7 were found in 10 (6.4%) specimens. Children aged two years or younger had
      the highest occurrence of Cryptosporidium (4.4%) and Enterocytozoon (13.0%) while
      children of 6 to 17 years had the highest Giardia infection rate (40.0%). No
      Cryptosporidium, Giardia, and Enterocytozoon were detected in patients older than
      60 years. Enterocytozoon had high infection rates in both HIV-positive (3.3%) and
      HIV-negative (8.3%) patients. Results of the study suggest that anthroponotic
      transmission may be important in the transmission of Cryptosporidium spp. and G.
      duodenalis while zoonotic transmissions may also play a role in the transmission
      of E. bieneusi in humans in Kaduna State, Nigeria.

PMID- 22664353
TI  - Reconstruction of electrical impedance tomography (EIT) images based on the
      expectation maximum (EM) method.
AB  - Electrical impedance tomography (EIT) calculates the internal conductivity
      distribution within a body using electrical contact measurements. The image
      reconstruction for EIT is an inverse problem, which is both non-linear and ill
      posed. The traditional regularization method cannot avoid introducing negative
      values in the solution. The negativity of the solution produces artifacts in
      reconstructed images in presence of noise. A statistical method, namely, the
      expectation maximization (EM) method, is used to solve the inverse problem for
      EIT in this paper. The mathematical model of EIT is transformed to the non
      negatively constrained likelihood minimization problem. The solution is obtained
      by the gradient projection-reduced Newton (GPRN) iteration method. This paper
      also discusses the strategies of choosing parameters. Simulation and experimental
      results indicate that the reconstructed images with higher quality can be
      obtained by the EM method, compared with the traditional Tikhonov and conjugate
      gradient (CG) methods, even with non-negative processing.

PMID- 22664354
TI  - Chronic restraint stress causes anxiety- and depression-like behaviors,
      downregulates glucocorticoid receptor expression, and attenuates glutamate
      release induced by brain-derived neurotrophic factor in the prefrontal cortex.
AB  - Stress and the resulting increase in glucocorticoid levels have been implicated
      in the pathophysiology of depressive disorders. We investigated the effects of
      chronic restraint stress (CRS: 6 hours * 28 days) on anxiety- and depression-like
      behaviors in rats and on the possible changes in glucocorticoid receptor (GR)
      expression as well as brain-derived neurotrophic factor (BDNF)-dependent neural
      function in the prefrontal cortex (PFC). We observed significant reductions in
      body weight gain, food intake and sucrose preference from 1 week after the onset
      of CRS. In the 5th week of CRS, we conducted open-field (OFT), elevated plus-maze
      (EPM) and forced swim tests (FST). We observed a decrease in the number of
      entries into open arms during the EPM (anxiety-like behavior) and increased
      immobility during the FST (depression-like behavior). When the PFC was removed
      after CRS and subject to western blot analysis, the GR expression reduced
      compared with control, while the levels of BDNF and its receptors remained
      unchanged. Basal glutamate concentrations in PFC acute slice which were measured
      by high performance liquid chromatography were not influenced by CRS. However,
      BDNF-induced glutamate release was attenuated after CRS. These results suggest
      that reduced GR expression and altered BDNF function may be involved in chronic
      stress-induced anxiety--and depression-like behaviors.

PMID- 22664355
TI  - A massive adenoid cystic carcinoma of nasal septum progressed into the skull
      base.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) is a malignant tumor commonly
      occurring in the major salivary glands. ACC of the nasal septum is exceeding
      rare. METHODS: The case of a 42-year-old woman with ACC of the nasal septum is
      presented. Her chief complaint was nasal obstruction and dysosmia for two month.
      CT and MRI demonstrated a massive mass occupying the nasal septum infiltrating
      the palate, vomeronasal, anterior skull base, and dura mater. Combined anterior
      cranial surgery, endoscopic intranasal surgery, and transpalatal surgery were
      selected due to the size and location of the tumor. A negative surgical margin
      was achieved without cosmetic deformity or functional disorder. RESULTS: She had
      postoperative radiotherapy with no recurrence or distant metastasis during the
      follow-up period. CONCLUSION: The tumor location and the perineural spread
      pattern should be considered to determine the treatment plan for septum ACC. Post
      operative radiation is now generally recommended. ACC has a high incidence of
      local recurrence and distant metastasis rate; therefore, long-term follow-up is
      necessary.

PMID- 22664356
TI  - Production of hepatitis B defective particles is dependent on liver status.
AB  - Defective hepatitis B virus (dHBV) generated from spliced RNA is detected in the
      sera of HBV-chronic carriers. Our study was designed to determine whether the
      proportion of dHBV changed during the course of infection, and to investigate
      whether dHBV might interfere with HBV replication. To achieve this, HBV wild-type
      and dHBV levels were determined by Q-PCR in sera from 56 untreated chronic
      patients and 23 acute patients, in sequential samples from 4 treated-patients and
      from liver-humanized mice after HBV infection. The proportion of dHBV was higher
      in patients with severe compared to null/moderate liver disease or with acute
      infection. Follow-up showed that the proportion of dHBV increased during disease
      progression. By contrast, a low and stable proportion of dHBV was observed in the
      humanized-mouse model of HBV infection. Our results highlight a regulation of the
      proportion of dHBV during liver disease progression that is independent of
      interference with viral replication.

PMID- 22664357
TI  - Mutational analysis of residues involved in nucleotide and divalent cation
      stabilization in the rotavirus RNA-dependent RNA polymerase catalytic pocket.
AB  - The rotavirus RNA-dependent RNA polymerase (RdRp), VP1, contains canonical RdRp
      motifs and a priming loop that is hypothesized to undergo conformational
      rearrangements during RNA synthesis. In the absence of viral core shell protein
      VP2, VP1 fails to interact stably with divalent cations or nucleotides and has a
      retracted priming loop. To identify residues of potential import to nucleotide
      and divalent cation stabilization, we aligned VP1 of divergent rotaviruses and
      the structural homolog reovirus lambda3. VP1 mutants were engineered and
      characterized for RNA synthetic capacity in vitro. Conserved aspartic acids in
      RdRp motifs A and C and arginines in motif F that likely stabilize divalent
      cations and nucleotides were required for efficient RNA synthesis. Mutation of
      individual priming loop residues diminished or enhanced RNA synthesis efficiency
      without obviating the need for VP2, which suggests that this structure serves as
      a dynamic regulatory element that links RdRp activity to particle assembly.

PMID- 22664358
TI  - Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles
      (SLNs): development, characterizations and comparative evaluations of
      clotrimazole-loaded SLNs and NLCs?
AB  - In recent years, solid lipid nanoparticles (SLNs) and nanostructured lipid
      carriers (NLCs) are among the popular research topics for the delivery of
      lipophilic drugs. Although SLNs have demonstrated several beneficial properties
      as drug-carrier, limited drug-loading and expulsion of drug during storage led to
      the development of NLCs. However, the superiority of NLCs over SLNs has not been
      fully established yet due to the contradictory results. In this study, SLNs and
      NLCs were developed using clotrimazole as model drug. Size, polydispersity index
      (PI), zeta potential (ZP), drug-loading (L), drug encapsulation efficiency (EE),
      scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X
      ray diffractometry (XRD), drug release and stability of SLNs and NLCs were
      compared. Critical process parameters exhibited significant impact on the
      nanoparticles' properties. Size, PI, ZP and EE of the developed SLNs and NLCs
      were<100 nm, <0.17, <-22 mV and>82%, respectively. SEM images of SLNs and NLCs
      revealed spherical shaped particles (~ 100 nm). DSC and XRD studies indicated
      slight difference between SLNs and NLCs as well as disappearance of the
      crystalline peak(s) of the encapsulated drug. NLCs demonstrated faster drug
      release than SLNs at low drug-loading, whereas there was no significant
      difference in drug release from SLNs and NLCs at high drug-loading. However,
      sustained/prolonged drug release was observed from both formulations.
      Furthermore, this study suggests that the drug release experiment should be
      designed considering the final application (topical/oral/parenteral) of the
      product. Regarding stability, NLCs showed better stability (in terms of size, PI,
      EE and L) than SLNs at 25 degrees C. Moreover, there was no significant
      difference in drug release profile of NLCs after 3 months storage in compare to
      fresh NLCs, while significant change in drug release rate was observed in case of
      SLNs. Therefore, NLCs have an edge over SLNs.

PMID- 22664359
TI  - Real-time monitoring of superoxide generation and cytotoxicity in neuroblastoma
      mitochondria induced by 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline.
AB  - The potential neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline
      (TaClo) has recently been suggested to be a causative factor in the clinical
      development of parkinsonian symptoms after long-term exposure to precursor
      compounds such as the hypnotic chloral hydrate. TaClo is known to cause cell
      death in dopaminergic neuronal cells, however, the pathway and mechanisms remain
      undefined. This study reports for the first time that TaClo promotes cytotoxicity
      in SH-SY5Y neuroblastoma cells within 2 hours of initial exposure. TaClo also
      caused superoxide production from isolated mitochondria, which was comparable in
      response time and magnitude to production elicited by more established
      respiratory inhibitors such as rotenone and antimycin A. These findings present
      new evidence in support of TaClo-induced neuronal death via superoxide signalling
      and oxidative stress.

PMID- 22664360
TI  - Normal bone turnover in transient hyperphosphatasemia.
AB  - Transient hyperphosphatasemia of infancy and early childhood (THI) is
      characterized by a temporary isolated elevation of serum alkaline phosphatase
      activity (ALP), predominantly its bone or liver isoform, in either sick or
      healthy children under 5 years of age. Return to normal ALP levels usually occurs
      within four months. Spontaneous rise of ALP might concern the physician,
      especially when treating seriously ill children. However, THI is considered a
      benign biochemical disorder with no clinical consequences. Some existing reports
      support the hypothesis that THI is a result of increased bone turnover. We
      present evidence of normal bone turnover in two children with THI. In a one-year
      old girl and a boy of the same age, high ALP levels (31 and 109 ukat/L,
      respectively) were accidentally detected. The children had no signs of metabolic
      bone disease or of liver disease. The high ALP levels returned to normal in two
      months, thus fulfilling the diagnosis of THI. In both patients, serum parathyroid
      hormone and bone turnover markers, serum CrossLaps, and serum osteocalcin were
      neither elevated, nor did these markers follow the ALP dynamics, thus reflecting
      normal bone turnover in THI. Children with THI should be spared from extensive
      investigations and unnecessary vitamin D treatment.

PMID- 22664361
TI  - A giant ovarian cyst in a neonate with classical  21-hydroxylase deficiency with
      very high testosterone levels demonstrating a high-dose hook effect.
AB  - Congenital adrenal hyperplasia (CAH) is a group of disorders affecting the
      adrenal steroid synthesis. The most common form, 21-hydroxylase deficiency (21
      OHD), leads to decreased production of cortisol and aldosterone with increased
      androgen secretion. In classic CAH, glucocorticoid treatment can be life-saving
      and serves to bring the symptoms under control. However, the treatment challenge
      is to effectively control the excess androgen effect by using the lowest possible
      glucocorticoid dose. Previous studies suggested a relationship between ovarian
      cyst formation and adrenal androgen excess, but neonatal large ovarian cysts have
      been very rarely reported in newborns with CAH. Here, we present the unique case
      of a neonate with classical 21-OHD who underwent surgery for a giant (10x8x7 cm)
      unilateral solitary ovarian follicular cyst on the 2nd postnatal day. Hormonal
      evaluation of the patient revealed high-dose hook effect for serum testosterone
      levels for the first time by a two-site immunoradiometric assay. Possible
      mechanisms by which androgen excess may cause ovarian cyst formation are
      discussed.

PMID- 22664362
TI  - Body weight, length and head circumference at birth in a cohort of Turkish
      newborns.
AB  - OBJECTIVE: Intrauterine growth references are primarily useful indicators in the
      assessment of the general health status of newborn infants. Although Lubchenco's
      references are still used in many neonatal care units, we believe that there is a
      need for up-to-date intrauterine growth references specific for different
      populations. To develop gestational age-and gender-specific national references
      for birth weight, birth length and head circumference. METHODS: Data were
      collected from neonatal records of perinatology services of eleven hospitals from
      January to December 2009. The anthropometry of a total of 4750 singleton live
      births born between 28 and 41 weeks of gestation were recorded. Means and
      standard deviations were calculated, and percentiles for each gender and
      gestational week were produced using the LMS program. The results were compared
      with US infants and also with local data. RESULTS: Gestational age- and gender
      specific 3rd, 5th, 10th, 15th, 25th, 50th, 75th, 85th, 90th, 95th and 97th
      percentile values were produced. Comparison of the 10th, 50th and 90th percentile
      values showed that the boys were heavier and longer than the girls. Head
      circumference values were also higher in the boys. Proportions of small for
      gestational age (SGA), appropriate for gestational age (AGA) and large for
      gestational age (LGA) infants in the sample were 10.1%, 79.1% and 10.8%,
      respectively. CONCLUSION: These gender- and gestational age-specific references
      will be of use in clinical practice and also for research purposes until more
      comprehensive, reliable and accessible national data pertaining to the
      intrauterine growth of Turkish infants are produced.

PMID- 22664363
TI  - Kidney dysfunction at the time of intracerebral hemorrhage is associated with
      increased in-hospital mortality: a retrospective observational cohort study.
AB  - OBJECTIVE: Renal dysfunction has been implicated as a risk factor for adverse
      outcomes after numerous cardiovascular events including stroke. However, most of
      the stroke studies have focused on long-term results and have primarily examined
      ischemic stroke. Therefore, we aimed to determine if renal dysfunction was
      associated with increased initial in-hospital mortality after intracerbral
      hemorrhage (ICH). METHODS: Our retrospective, observational, cohort chart review
      evaluated the relationship between in-hospital mortality after ICH and renal
      function, assessed from admission estimated glomerular filtration rate (eGFR),
      calculated using the abbreviated modification of diet in renal disease equation,
      in 101 consecutive cases. RESULTS: Survivors had higher admission eGFRs than
      those who died (88 +/- 37 versus 59 +/- 33 ml/minute/1.73 m(2); P<0.001).
      Similarly, mortality was higher in patients with eGFR <90 versus those >90
      ml/minute/1.73 m(2) (40% versus 15%; P = 0.009). Univariate analysis indicated
      that in-hospital death was associated with intraventricular hemorrhage, ICH
      volume, age, eGFR <90 ml/minute/1.73 m(2), and admission values of serum
      creatinine, and blood urea nitrogen (P<0.05). Multivariable logistic regression
      (controlled for confounding variables) revealed that admission eGFR was an
      independent predictor of death; odds ratio 0.96; 95% confidence interval 0.92
      0.99. We also found a negative correlation between eGFR and lesion size (P =
      0.041); the lower the eGFR, the larger the lesion. CONCLUSION: Renal dysfunction
      was an independent predictor of initial in-hospital mortality after stroke and
      hence may stratify risk in ICH patients.

PMID- 22664365
TI  - Depression and heart failure.

PMID- 22664364
TI  - Prognostic value of adenosine stress perfusion cardiac MRI with late gadolinium
      enhancement in an intermediate cardiovascular risk population.
AB  - BACKGROUND: The high diagnostic accuracy of adenosine stress cardiac magnetic
      resonance (AS-CMR) for detecting coronary artery stenoses, with high sensitivity
      and specificity, is well documented. Prognostic data, particularly in non-low
      risk study populations and for greater than 12 months of follow up, is however
      lacking or variable in its findings. We present prognostic data, in an
      intermediate cardiovascular risk cohort undergoing adenosine stress perfusion
      CMR, over approximately 2 years of follow up. METHODS: The study population
      comprised 362 patients referred for a clinically indicated stress CMR and
      included patients with proven coronary artery disease (CAD; n=157) or unknown CAD
      status, yet an intermediate cardiovascular risk profile (n=205). Perfusion
      imaging was performed at stress (adenosine 140 MUg/kg/min) and rest on a 1.5 T
      system. Patient records and state-wide hospital databases were reviewed. Major
      adverse cardiac events--death, myocardial infarction, revascularisation or
      ischaemic hospitalisation--were evaluated over a median follow up of 22 months.
      RESULTS: Of the 362 cases, 90 had a stress perfusion CMR positive for ischaemia
      and experienced a MACE rate of 24%. Of the 272 negative CMR scans, 225 were also
      negative for late gadolinium enhancement, and in this group MACE was encountered
      in only 6 (2.7%) patients. Accordingly a negative stress CMR afforded a freedom
      from MACE of 97.3%. Freedom from death/myocardial infarction was 99.6%.
      CONCLUSIONS: In patients with confirmed coronary artery disease or at
      intermediate risk for cardiovascular events, a negative stress perfusion CMR is
      associated with an excellent prognosis over nearly 2 years of follow up.

PMID- 22664366
TI  - Bi-ostial coronary thrombosis due to heparin induced thrombocytopenia.

PMID- 22664367
TI  - Drug-eluting stents increase late mortality compared with coronary artery bypass
      grafting in triple-vessel disease: a meta-analysis of randomized controlled and
      risk-adjusted observational studies.

PMID- 22664368
TI  - Effects of exercise training for heart failure with preserved ejection fraction:
      a systematic review and meta-analysis of comparative studies.
AB  - INTRODUCTION: We conducted a systematic review to assess the effect of exercise
      training in patients with heart failure with preserved ejection fraction (HFPEF).
      METHODS: A number of electronic databases were searched up to November 2011 to
      identify comparative studies of exercise training in HFPEF. Where possible,
      outcome data from included studies were pooled using meta-analysis. RESULTS:
      Three randomised controlled trials, one non-randomised controlled trial and one
      pre-post study were included, for a total of 228 individuals. The combined
      duration of exercise programmes and follow-up ranged from 12 to 24 weeks. No
      deaths, hospital admissions or serious adverse events were observed during or
      immediately following exercise training. Compared to control, the change in
      exercise capacity at follow-up was higher with exercise training (between group
      mean difference: 3.0 ml/kg/min, 95% CI: 2.4 to 2.6). In the four studies, that
      reported the Minnesota Living with Heart Failure questionnaire, there was
      evidence of a larger gain in health-related quality of life with exercise
      training (7.3 units, 3.3 to 11.4). The largest study showed some evidence of
      improvement in the E/E' ratio with exercise training, but this was not confirmed
      in the other studies (overall -0.9, -3.8 to 2.0); E/A ratios were not changed.
      CONCLUSIONS: Exercise training for patients with HFPEF confers benefit in terms
      of enhancements in exercise capacity and health-related quality of life and
      appears to be safe. The impact on diastolic function remains unclear. Further
      trials should provide data on long term effects, prognostic relevance and cost
      effectiveness.

PMID- 22664369
TI  - Oxygen and natriuretic peptide secretion from the heart.

PMID- 22664370
TI  - Brugada electrocardiogram associated with pulmonary embolism.

PMID- 22664372
TI  - Beta-90Sr irradiation treatment of silicon wafer coated with extracellular matrix
      protein to mimic the beta-32P radiation application in intravascular
      brachytherapy.

PMID- 22664371
TI  - Comparison of long-term outcomes in STEMI and NSTE-ACS after coronary stent
      placement: an analysis in a real world BMS and DES population.
AB  - BACKGROUND/OBJECTIVES: The prognostic difference between STEMI and NSTE-ACS after
      coronary stent placement remains unclear. We aimed to compare the short- and long
      term event rates in patients presenting with ST-segment elevation myocardial
      infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE
      ACS) after percutaneous coronary intervention (PCI) with either bare-metal stents
      (BMS) or drug-eluting stents (DES). METHODS: Between 2000 and 2005 a total of
      1749 STEMI and 1921 NSTE-ACS patients received either a BMS or DES in consecutive
      real world cohorts. Descriptive statistics and multivariate survival analyses
      were applied to compare the event rates in STEMI and NSTE-ACS during 4 years
      follow-up. RESULTS: NSTE-ACS patients had significantly higher clinical and
      angiographic risk profiles at baseline and were treated with less optimal medical
      therapy during follow-up. At 4 years follow-up, all-cause mortality was
      significantly higher in STEMI compared to NSTE-ACS after coronary stent placement
      (17.4% vs. 14.3%; HR 1.60, 95% CI 1.24-2.07). In a landmark analysis no
      difference was seen in all-cause mortality among STEMI en NSTE-ACS between 1
      month and 4 years follow-up (HR 1.10, 95% CI 0.81-1.51). Cardiac death was more
      prevalent in STEMI patients, while the 4-year cumulative incidences of any
      myocardial infarction, any coronary revascularization, target lesion
      revascularization and definite stent thrombosis were similar in both ACS groups.
      CONCLUSIONS: Patients presenting with STEMI have a worse long-term prognosis
      compared to NSTE-ACS after coronary stent placement, due to higher short-term
      death rates. However, after the first month STEMI and NSTE-ACS patients have a
      comparable long-term survival.

PMID- 22664373
TI  - Proteomics of DF-1 cells infected with avian leukosis virus subgroup J.
AB  - Avian leukosis virus subgroup J (ALV-J) is an avian oncogenic retrovirus that has
      led to severe economic losses in the poultry industry in China in recent years.
      The pathogenesis of virus infection and virus-host interactions are still not
      well elucidated. In this paper, we investigated the expression changes for
      cellular proteins in DF-1 cells infected with ALV-J. Comparative analyses
      revealed that the majority of the altered proteins in DF-1 cells appeared at 6
      12h after ALV-J infection. Mass spectrometry identified 74 altered cellular
      proteins, including 30 up-regulated proteins and 44 down-regulated proteins. Some
      of these proteins are involved in cell cytoskeleton, metabolic processes,
      response to stimulus and immune responses. Other proteins, such as DJ-1, UCHL1,
      VDAC1 and HMGB1, have some relationship to apoptosis or oncogenesis. The changes
      in the transcriptional profile of DJ-1, UCHL1, VDAC1 and HMGB1 in infected as
      compared to uninfected DF-1 cells were confirmed by real-time RT-PCR. Our work
      gives some information about differential protein expression in cells infected
      with ALV-J, which will help us to understand viral pathogenicity.

PMID- 22664374
TI  - High resolution melting analysis for the identification of novel mutations in
      DKC1 and TERT genes in patients with dyskeratosis congenita.
AB  - Dyskeratosis congenita (DC) is a rare inherited bone-marrow failure syndrome with
      high clinical heterogeneity. Cells derived from DC patients present short
      telomeres at early ages, as a result of mutations in genes encoding components of
      the telomerase complex (DKC1, TERC, TERT, NHP2 and NOP10), or the shelterin
      complex (TINF2). However, mutations have been identified only in around 50% of
      the cases, indicating that other genes could be involved in the development of
      this disease. Indeed, mutations in TCBA1 or chromosome segment C16orf57 have been
      described recently. We have used HRM technology to perform genetic analysis in
      the above mentioned genes, in Spanish patients showing both, some clinical
      features of DC and short telomeres. The mutations have been identified by PCR
      amplification of DC genes followed by high resolution melting (HRM) and direct
      DNA sequencing analysis. We have identified seven new families with DC, three
      with X-linked DC and four with autosomal dominant DC, in which we have found two
      novel mutations in DKC1 (p.His68Arg and p.Lys390del) and four novel mutations in
      TERT gene (p.Pro530Leu, p.Arg698Trp, p.Arg971His and p.Arg698Gln). The results
      show that the use of HRM analysis enables a rapid and inexpensive identification
      of mutations in dyskeratosis congenita associated genes.

PMID- 22664375
TI  - Emotional stimuli capture spatial attention but do not modulate spatial memory.
AB  - There is evidence that emotional stimuli capture spatial attention and that
      visual memory is enhanced for emotional content. Here we examine the relationship
      between emotional content of stimuli and interactions with spatial memory. To
      assess spatial memory, a modified version of the Corsi Blocks Task (CBT),
      utilising emotional stimuli, was employed. In the CBT a series of spatial
      positions are highlighted and the participant has to repeat these in the order in
      which they were produced. Results showed that presenting more meaningful stimuli,
      such as emotional faces (e.g. angry or happy) at the spatial locations in the CBT
      did not enhance spatial memory span relative to the presentation of neutral
      stimuli (e.g. neutral faces) or non-image stimuli signified by a change in the
      luminance of the blocks. In addition, saccadic eye movements performed during
      retention disrupted spatial memory for all items. This occurred irrespective of
      whether the item to be remembered was a face, a luminance-defined stimulus or
      whether the face carried emotional significance. The results were not related to
      the visibility of the test stimuli as participants recognised the emotion
      displayed by the faces significantly above chance and rated emotional faces as
      being more arousing than neutral faces. Changes in the type of emotional stimulus
      (e.g. fearful faces, emotional schematic faces, spiders or flowers) or encoding
      (short vs. long) duration did not alter the pattern of results. These findings
      demonstrate an important dissociation between spatial capture and memory.
      Although emotional content can modulate orienting behaviour, it appears to be of
      limited effect on spatial memory.

PMID- 22664376
TI  - Major clonal lineages in impetigo Staphylococcus aureus strains isolated in Czech
      and Slovak maternity hospitals.
AB  - One hundred and twenty-seven exfoliative toxin-producing (ET-positive) strains of
      Staphylococcus aureus collected in 23 Czech and one Slovak maternity hospitals
      from 1998 to 2011 were genotypically characterized by multilocus sequence typing
      (MLST), pulsed-field gel electrophoresis (PFGE) profiling, spa gene polymorphism
      analysis, and ETA-converting prophage carriage, which resulted in the
      identification of 21 genotypes grouped into 4 clonal complexes (CC). Ninety-one
      isolates carried the eta gene alone whilst 12 isolates harboured only the etb
      gene. Two new, to date not defined, spa types (t6644 and t6645) and 2 novel
      sequence types (ST2194 and ST2195) were identified in the set of strains under
      study. The predominant CC121 occurred in 13 Czech hospitals. CC15, CC9, and ST88
      (CC88) exclusively included eta gene-positive strains while the strains belonging
      to ST121 harboured the eta and/or etb genes. This study highlights not only
      significant genomic diversity among impetigo strains and the distribution of
      major genotypes disseminated in the Czech and Slovak maternity hospitals, but
      also reveals their impact in epidermolytic infections.

PMID- 22664377
TI  - Doxorubicin selects for fluconazole-resistant petite mutants in Candida glabrata
      isolates.
AB  - Candida infections are a permanent threat to immunocompromised individuals such
      as cancer patients, and Candida glabrata has emerged as a major problem in recent
      years. Resistance may develop during lengthy antifungal therapies and is often
      mediated by upregulation of fungal drug efflux pumps. During chemotherapy the
      yeast cell is also exposed to cytotoxic agents that may affect its drug
      susceptibility. Four C. glabrata isolates, three susceptible and one resistant to
      fluconazole (FLU), were incubated with 20 MUg/ml of doxorubicin (DOX) for 90 min.
      In a second experiment, the isolates were cultured with DOX for ten days. Samples
      were taken on subsequent days to determine the minimal inhibitory concentration
      (MIC) of FLU and to analyze expression of CgCDR1, CgCDR2, CgSNQ2 and CgPDR1.
      Samples were also used to assess the petite phenotype. Short-term DOX exposure
      did not induce efflux pump gene expression, but genes were consistently
      overexpressed in FLU-susceptible isolates during long-term exposure. An increase
      in MIC values on day 6 in two of the isolates coincided with the first occurrence
      of petite mutants in all susceptible isolates. The respiratory deficiency of
      selected petite mutants was confirmed by culturing mutants on agar containing
      glycerol as the sole carbon source. FLU MIC values for respiratory-deficient
      clones were >=64 MUg/ml, and efflux pump gene expression was greatly increased.
      The resistant isolate did not develop mitochondrial dysfunction. In summary, the
      cytotoxic agent DOX selects for FLU-resistant respiratory-deficient C. glabrata
      mutants, which may affect antifungal therapy.

PMID- 22664378
TI  - Antibodies for all: The case for genome-wide affinity reagents.
AB  - For more than 30 years, the production of research antibodies has been dominated
      by hybridoma technologies, while modern recombinant technologies have lagged
      behind. Here I discuss why this situation must change if we are to generate
      reliable, comprehensive reagent sets on a genome-wide scale, and I describe how a
      cultural shift in the research community could revolutionize and modernize the
      affinity reagent field. In turn, such a revolution would pay huge dividends by
      closing the gap between basic research and therapeutic development, thus enabling
      the development of myriad new therapies for unmet medical needs.

PMID- 22664379
TI  - Regulatory modules: Coupling protein stability to phopshoregulation during cell
      division.
AB  - Multiple post-translational regulation systems regulate cell biology. Two key
      mechanisms that coordinate the myriad processes of cell replication are
      phosphorylation and ubiquitin-mediated degradation of proteins. Regulatory
      modules have evolved to integrate these two control systems at key decision
      points in the cell division cycle. These modules enable information to be
      processed with high fidelity by filtering noise, improving specificity,
      generating feedback loops, and optimizing spatiotemporal coordination of cellular
      processes. This review provides examples of these modules and considers the
      advantages of this signaling nexus.

PMID- 22664380
TI  - Approaches to providing missing transfer parameter values in the ERICA Tool--how
      well do they work?
AB  - A required parameter for the ERICA Tool is the concentration ratio (CR), which is
      used to describe the transfer from environmental media to a range of organisms.
      For the original parameterisation of the ERICA Tool, 60% of these values were
      derived using a variety of extrapolation approaches, including the application of
      allometric models, the use of values for a similar organism or element with
      similar biogeochemical behaviour and the use of values from a different
      ecosystem. Although similar approaches are applied in other assessment systems,
      there has been little attempt to see how well these approaches perform. In this
      paper, CR values in the ERICA Tool derived using extrapolation approaches are
      compared to more recently available empirical data from the IAEA wildlife
      transfer database. The primary purpose of the default CR database in the ERICA
      Tool, and other models, is to enable the user to conduct conservative screening
      assessments. Conservatism was therefore introduced to the analyses by selecting
      the 95th percentile CR values for subsequent calculations. The extrapolation
      methodologies are not guaranteed to provide conservative estimates of empirical
      95th percentile CRs. For the terrestrial ecosystem, the extrapolation methods
      provide underpredictions of empirical 95th percentiles as often as they produce
      overpredictions. In a few cases the underestimation of CR values, when
      considering all ecosystems, is substantial - by orders of magnitude - which is
      clearly unacceptable for a screening assessment. Thus, although extrapolation
      approaches will remain an essential component of screening assessments in the
      future, because data gaps will always be present, diligence is important in their
      application. Finally, by synthesizing the results from the current analyses and
      through other considerations, some recommendations are provided with regards to
      modifying the original guidance on use of extrapolation approaches in the ERICA
      Tool. 

PMID- 22664381
TI  - Statistical regularities in the distribution of radionuclides in sediments of
      Transcarpathia mountain rivers.
AB  - The results of the low-background gamma-spectrometric measurements of sediments
      from three Western Carpathian mountain rivers during a three year term (2006
      2009) are presented. These sediments are dynamic and very informative for
      environmental monitoring of a large watershed. Distances between the river sample
      points were 10-20 km and the total change of the altitude was 200-400 m. The
      proposed sampling scheme allows to investigate the changes of seasonal and
      spatial distributions of the radionuclides in sediment. The statistical
      correlations between the sampling points, the water level of the river and the
      contents of natural or anthropogenic radionuclides in sediment were studied. The
      effect of the intensive leaching of radionuclides from sediments during the flood
      season is shown and this can be considered as the principal self-purification
      mechanism.

PMID- 22664382
TI  - In situ enzymatic silver enhancement based on functionalized graphene oxide and
      layer-by-layer assembled gold nanoparticles for ultrasensitive detection of
      thrombin.
AB  - A highly specific in situ amplification strategy was designed for ultrasensitive
      detection of thrombin by combining the layer-by-layer (LBL) assembled
      amplification with alkaline phosphatase (ALP) and gold nanoparticles (Au)
      mediated silver deposition. High-density carboxyl functionalized graphene oxide
      (FGO) was introduced as a nanocarrier for LBL assembling of alkaline phosphatase
      decorated gold nanoparticles (ALP-Au), which was further adopted to label
      thrombin aptamer II. After sandwich-type reaction, numerous ALP were captured
      onto the aptasensor surface and catalyzed the hydrolysis of ascorbic acid 2
      phosphate (AAP), which in situ generated ascorbic acid (AA), reducing Ag(+) to Ag
      nanoparticles (AgNPs) for electrochemical readout. Inspiringly, the in situ
      amplification strategy with ethanolamine as an effective blocking agent showed
      remarkable amplification efficiency, very little nonspecific adsorption, and low
      background signal, which was favorable to enhance the sensitivity of aptasensor.
      Our novel dramatic signal amplification strategy, with a detection limit of 2.7
      fM, showed about 2-3 orders of magnitude improvement in the sensitivity for
      thrombin detection compared to other universal enzyme-based electrochemical
      assay.

PMID- 22664383
TI  - Lens-free shadow image based high-throughput continuous cell monitoring
      technique.
AB  - A high-throughput continuous cell monitoring technique which does not require any
      labeling reagents or destruction of the specimen is demonstrated. More than 6000
      human alveolar epithelial A549 cells are monitored for up to 72 h simultaneously
      and continuously with a single digital image within a cost and space effective
      lens-free shadow imaging platform. In an experiment performed within a custom
      built incubator integrated with the lens-free shadow imaging platform, the cell
      nucleus division process could be successfully characterized by calculating the
      signal-to-noise ratios (SNRs) and the shadow diameters (SDs) of the cell shadow
      patterns. The versatile nature of this platform also enabled a single cell
      viability test followed by live cell counting. This study firstly shows that the
      lens-free shadow imaging technique can provide a continuous cell monitoring
      without any staining/labeling reagent and destruction of the specimen. This high
      throughput continuous cell monitoring technique based on lens-free shadow imaging
      may be widely utilized as a compact, low-cost, and high-throughput cell
      monitoring tool in the fields of drug and food screening or cell proliferation
      and viability testing.

PMID- 22664385
TI  - Molecular cloning of novel alternatively spliced variants of BCL2L12, a new
      member of the BCL2 gene family, and their expression analysis in cancer cells.
AB  - In the past, we identified and cloned the BCL2-like 12 (BCL2L12) gene, a novel
      member of the BCL2 family, which is implicated in various malignancies. The
      classical BCL2L12 protein isoform contains a highly conserved BH2 domain, a BH3
      like motif, and a proline-rich region, and is involved in apoptosis. Most members
      of this apoptosis-related family are subjected to alternative splicing, thus
      generating multiple protein isoforms with distinct properties, and sometimes even
      with opposite function (pro- vs. anti-apoptotic). In the current study, we report
      the identification, molecular cloning, and expression pattern of novel splice
      variants of the human BCL2L12 gene in cancer cell lines. EST clones displaying
      high sequence identity (>=90%) with the classical BCL2L12 transcript were
      aligned, in order to identify those containing at least one novel splice
      junction. EST database mining led to the identification of three previously
      unknown splice variants of this apoptotic gene. In our effort to experimentally
      validate these novel transcripts, we also cloned seven more, previously
      unidentified, BCL2L12 alternatively spliced variants. Expression analysis of all
      BCL2L12 splice variants in human cancer cell lines and embryonic kidney cells
      revealed remarkable differences between their BCL2L12 expression profiles.
      Interestingly, 7 out of 10 novel splice variants of BCL2L12 are predicted to
      encode new protein isoforms, some of which are BH3-only proteins, in contrast to
      the classical BCL2L12 isoform, which also contains a functional BH2 domain. The
      remaining three novel splice variants of BCL2L12 are nonsense-mediated mRNA decay
      (NMD) candidates.

PMID- 22664384
TI  - Using crowdsourcing technology for testing multilingual public health promotion
      materials.
AB  - BACKGROUND: Effective communication of public health messages is a key strategy
      for health promotion by public health agencies. Creating effective health
      promotion materials requires careful message design and feedback from
      representatives of target populations. This is particularly true when the target
      audiences are hard to reach as limited English proficiency groups. Traditional
      methods of soliciting feedback--such as focus groups and convenience sample
      interviews--are expensive and time consuming. As a result, adequate feedback from
      target populations is often insufficient due to the time and resource constraints
      characteristic to public health. OBJECTIVE: To describe a pilot study
      investigating the use of crowdsourcing technology as a method to gather rapid and
      relevant feedback on the design of health promotion messages for oral health. Our
      goal was to better describe the demographics of participants responding to a
      crowdsourcing survey and to test whether crowdsourcing could be used to gather
      feedback from English-speaking and Spanish-speaking participants in a short
      period of time and at relatively low costs. METHODS: We developed health
      promotion materials on pediatric dental health issues in four different formats
      and in two languages (English and Spanish). We then designed an online survey to
      elicit feedback on format preferences and made it available in both languages via
      the Amazon Mechanical Turk crowdsourcing platform. RESULTS: We surveyed 236
      native English-speaking and 163 native Spanish-speaking participants in less than
      12 days, at a cost of US $374. Overall, Spanish-speaking participants originated
      from a wider distribution of countries than the overall Latino population in the
      United States. Most participants were in the 18- to 29-year age range and had
      some college or graduate education. Participants provided valuable input for the
      health promotion material design. CONCLUSIONS: Our results indicate that
      crowdsourcing can be an effective method for recruiting and gaining feedback from
      English-speaking and Spanish-speaking people. Compared with traditional methods,
      crowdsourcing has the potential to reach more diverse populations than
      convenience sampling, while substantially reducing the time and cost of gathering
      participant feedback. More widespread adoption of this method could streamline
      the development of effective health promotion materials in multiple languages.

PMID- 22664387
TI  - Prolonged mechanical ventilation: new facilities and new models of care.

PMID- 22664386
TI  - Activation of adipogenesis by lipocalin-type prostaglandin D synthase-generated
      Delta12-PGJ2 acting through PPARgamma-dependent and independent pathways.
AB  - Lipocalin-type prostaglandin (PG) D synthase (L-PGDS)-produced PGD(2) accelerates
      adipogenesis. In this study, we investigated the molecular mechanism of PGD(2)
      mediated activation of adipogenesis in mouse adipocytic 3T3-L1 cells. LC/MS
      analysis showed that Delta(12)-PGJ(2), one of the PGD(2) metabolites, was
      predominantly produced in the differentiated 3T3-L1 cells. Delta(12)-PGJ(2)
      enhanced the expression of adipogenic genes in a Delta(12)-PGJ(2)-concentration
      dependent manner. Suppression of the expression of the adipogenic genes by L-PGDS
      siRNA or AT-56, an L-PGDS inhibitor, was cleared by the addition of Delta(12)
      PGJ(2). Moreover, the production of adiponectin and leptin was increased by
      treatment with Delta(12)-PGJ(2). Furthermore, the results of a mammalian two
      hybrid assay demonstrated that Delta(12)-PGJ(2) enhanced the PPARgamma-mediated
      transcription activity. However, Delta(12)-PGJ(2)-activated expression of
      adipogenic genes such as fatty acid binding protein 4 (aP2) and stearoyl-CoA
      desaturase was inhibited only at 38% and 42%, respectively, by treatment with
      GW9662, a PPARgamma antagonist in 3T3-L1 cells, although Troglitazone-mediated
      activation of the expression of these adipogenic genes was completely suppressed
      by GW9662, suggesting the existence of a PPARgamma-independent mechanism for
      Delta(12)-PGJ(2)-activated adipogenesis. These results, taken together, indicate
      that Delta(12)-PGJ(2) is a dominant metabolite of L-PGDS-produced PGD(2) during
      adipogenesis and acts as an activator for adipogenesis through both PPARgamma
      dependent and -independent mechanisms in 3T3-L1 cells.

PMID- 22664388
TI  - Sedimentary record of PAHs in the Liangtan River and its relation to
      socioeconomic development of Chongqing, Southwest China.
AB  - Concentrations of polycyclic aromatic hydrocarbons (PAHs) were detected in
      sediment cores and surface sediment samples from the Liangtan River of Chongqing,
      Southwest China. The total concentration of 16 PAHs ranged from 69 to 6251 ng g(
      1). The spatial distribution of the PAHs reflects the intensity and scope of
      human activity in the catchment. A historical record of PAH contamination was
      reconstructed using a sediment core from a background segment of the river. The
      characteristic changes of concentrations, fluxes and patterns of 16 PAHs over the
      past ~90years were captured in detail. An obvious peak of PAH concentration and
      flux was found in the 1940s, i.e., during war time, and then a sharp increase was
      observed from the early 1980s to the present. The maximum concentration and flux
      reached 1260 ng g(-1) and 470 ng cm(-2)year(-1), respectively. The sharp increase
      was attributed to the contribution of pyrogenic sources of PAHs. The population,
      length of highways and energy consumption of Chongqing, as indexes of
      socioeconomic development, were positively correlated with PAH input in the
      sediment core from the 1950s to the present. The results clearly show that the
      local socioeconomic development in the last decades remarkably aggravated the
      environmental load of sedimentary PAHs.

PMID- 22664389
TI  - Adsorption of mono- and di-butyltin by a wheat charcoal: pH effects and modeling.
AB  - Understanding adsorption processes of butyltins (BTs) such as monobutyltin (MBT)
      and dibutyltin (DBT) by black carbons is important for the evaluation of BT
      exposure risks to organisms and humans. However, relevant knowledge is scarce. In
      this study, the acidity constants pK(a,1)=2.3, pK(a,2)=3.5 and pK(a,3)=5.9 for
      MBT and pK(a,1)=3.0 and pK(a,2)=5.1 for DBT are estimated via potentiometric
      titration. Additionally, adsorption isotherms of BTs to a wheat charcoal were
      determined. The adsorption behavior was observed to be pH-dependent due to BT
      speciation and the pH-dependent surface charge of the charcoal. MBT adsorption to
      the charcoal decreases with increasing pH from 4 to 8, while the highest
      adsorption occurs at pH 6 for DBT. Adsorption of the BTs is successfully
      described in the pH range of 3-10 by using a newly developed pH-dependent Dual
      Langmuir model. The model has the potential to predict the interaction of BT
      species with charcoal, which can contribute to the risk assessments of BTs in the
      environment.

PMID- 22664390
TI  - The effects of biochars from rice residue on the formation of iron plaque and the
      accumulation of Cd, Zn, Pb, As in rice (Oryza sativa L.) seedlings.
AB  - A historically multi-metal contaminated soil was amended with biochars produced
      from different parts of rice plants (straw, husk and bran) to investigate how
      biochar can influence the mobility of Cd, Zn, Pb and As in rice seedlings (Oryza
      sativa L.). Rice shoot concentrations of Cd, Zn and Pb decreased by up to 98%,
      83% and 72%, respectively, due to biochar amendment, though that of As increased
      by up to 327%. Biochar amendments significantly decreased pore water
      concentrations (C(pw)) of Cd and Zn and increased that of As. For Pb it depended
      on the amendment. Porewater pH, dissolved organic carbon, dissolved phosphorus,
      silicon in pore water and iron plaque formation on root surfaces all increased
      significantly after the amendments. The proportions of Cd and Pb in iron plaque
      increased by factors 1.8-5.7 and 1.4-2.8, respectively; no increase was observed
      for As and Zn. Straw-char application significantly and noticeably decreased the
      plant transfer coefficients of Cd and Pb. This study, the first to investigate
      changes in metal mobility and iron plaque formation in rice plants due to
      amending a historically contaminated soil with biochar, indicates that biochar
      has a potential to decrease Cd, Zn and Pb accumulations in rice shoot but
      increase that of As. The main cause is likely biochar decreasing the C(pw) of Cd
      and Zn, increasing the C(pw) of As, and increasing the iron plaque blocking
      capacity for Cd and Pb.

PMID- 22664391
TI  - Induction of DNA fragmentation, chromosome aberrations and micronuclei by
      cisplatin in rat bone-marrow cells: protective effect of recombinant human
      erythropoietin.
AB  - Cisplatin (Cisp) is one of the most effective chemotherapeutic agents. However,
      at higher doses several side effects may occur. Recombinant human erythropoietin
      (rhEPO), a glycoprotein regulating haematopoiesis, has recently been shown to
      exert an important cyto-protective effects in many tissues. The purpose of this
      study was to explore whether rhEPO protects against Cisp-induced genotoxicity in
      rat bone-marrow cells. Adult male Wistar rats were divided into six groups of 18
      animals each: control group, rhEPO-alone group, Cisp-alone group and three
      rhEPO+Cisp-groups (pre-, co- and post-treatment condition, respectively). Our
      results show that Cisp induced a noticeable genotoxic effect in rat bone-marrow
      cells. In all types of treatment, rhEPO significantly decreased the frequency of
      micronuclei, the percentage of chromosome aberrations and the level of DNA
      damage. The protective effect of rhEPO was more efficient when it was
      administrated 24h before exposure to Cisp.

PMID- 22664392
TI  - New potential markers for the detection of boldenone misuse.
AB  - Boldenone is one of the most frequently detected anabolic androgenic steroids in
      doping control analysis. Boldenone misuse is commonly detected by the
      identification of the active drug and its main metabolite, 5beta-androst-1-en
      17beta-ol-3-one (BM1), by gas chromatography-mass spectrometry (GC-MS), after
      previous hydrolysis with beta-glucuronidase enzymes, extraction and
      derivatization steps. However, some cases of endogenous boldenone and BM1 have
      been reported. Nowadays, when these compounds are detected in urine at low
      concentrations, isotope ratio mass spectrometry (IRMS) analysis is needed to
      confirm their exogenous origin. The aim of the present study was to identify
      boldenone metabolites conjugated with sulphate and to evaluate their potential to
      improve the detection of boldenone misuse in sports. Boldenone was administered
      to a healthy volunteer and urine samples were collected up to 56h after
      administration. After a liquid-liquid extraction with ethyl acetate, urine
      extracts were analysed by liquid chromatography tandem mass spectrometry (LC
      MS/MS) using electrospray ionisation in negative mode by monitoring the
      transition of m/z 365-350, specific for boldenone sulphate. Boldenone sulphate
      was identified in the excretion study urine samples and, moreover, another peak
      with the same transition was observed. Based on the MS/MS behaviour the
      metabolite was identified as epiboldenone sulphate. The identity was confirmed by
      isolation of the LC peak, solvolysis and comparison of the retention time and
      MS/MS spectra with an epiboldenone standard. These sulphated metabolites have not
      been previously reported in humans and although they account for less than 1% of
      the administered dose, they were still present in urine when the concentrations
      of the major metabolites, boldenone and BM1, were at the level of endogenous
      origin. The sulphated metabolites were also detected in 10 urine samples tested
      positive to boldenone and BM1 by GC-MS. In order to verify the usefulness of
      these new metabolites to discriminate between endogenous and exogenous origin of
      boldenone, four samples containing endogenous boldenone and BM1, confirmed by
      IRMS, were analysed. In 3 of the 4 samples, neither boldenone sulphate nor
      epiboldenone sulphate were detected, confirming that these metabolites were
      mainly detected after exogenous administration of boldenone. In contrast,
      boldenone sulphate and, in some cases, epiboldenone sulphate were present in
      samples with low concentrations of exogenous boldenone and BM1. Thus, boldenone
      and epiboldenone sulphates are additional markers for the exogenous origin of
      boldenone and they can be used to reduce the number of samples to be analysed by
      IRMS. In samples with boldenone and BM1 at the concentrations suspicion for
      endogenous origin, only if boldenone and epiboldenone sulphates are present,
      further analysis by IRMS will be needed to confirm exogenous origin.

PMID- 22664393
TI  - Management of calcaneal fractures: what have we learnt over the years?
AB  - Calcaneal fractures result, in many cases, in, subtalar joint stiffness and
      severe disability. Diagnosis is usually made by X-ray, but more accurately by a
      computed tomography (CT) scan. In the last years, much has been known regarding
      its physiopathology and osteosynthesis. Although new developments in
      osteosynthesis materials have been made, calcaneus fractures still remains in
      dispute of those advocating non-operative treatment and those defending open
      reduction and internal fixation. Less invasive surgery, arthroscopy and three
      dimensional (3D) fluoroscopy are very important for reduction accuracy and soft
      tissue damage avoidance. In this article, the physiopathology, diagnosis,
      classification and treatment of calcaneus fractures are updated. Nevertheless,
      systematic reviews have shown no evidence about what treatment is better.

PMID- 22664394
TI  - Number of foods available at a meal determines the amount consumed.
AB  - The number of foods available at a meal has been suggested as a major determinant
      of the amount consumed. Two studies conducted in humans test this idea by
      altering the number of foods available at a meal where participants eat the
      available foods ad libitum. In Study 1, dinner intake of twenty-seven young
      adults was measured. The amount consumed was measured when subjects were served
      either: (a) a composite meal (a protein rich food, a carbohydrate rich food, and
      a vegetable), (b) a low carbohydrate meal (protein rich food and vegetable), or
      (c) a vegetarian meal (carbohydrate rich food and vegetable). In Study 2, twenty
      four subjects were given two different meals presented either as individual foods
      or as a composite meal (stir-fry or stew). Both studies show that the greater the
      number of foods offered at a meal, the greater the total intake. Study 2
      demonstrated that the effects observed in Study 1 could not be attributed to
      different nutrient compositions, but was rather due to the presentation of the
      individual foods because the same foods that were offered as individual foods
      were combined to make the composite meal. The results demonstrate that the
      greater the number of foods offered at a meal, the greater the spontaneous intake
      of those foods. This finding is important because not only does it expand the
      concept of variety from the kinds of foods to the number of foods, but it
      presents an environmental variable that might contribute to overeating and
      obesity.

PMID- 22664395
TI  - The perceptual threshold for overweight.
AB  - Normative, global overweight may play a prominent role in perpetuating the
      obesity epidemic via its contribution to weight-related norms that describe what
      is customary in a social environment. These weight-related norms include a
      perceptual standard determining where body weight shifts from normal to
      overweight. We introduce the construct of a perceptual threshold for overweight
      to identify this transition point. The perceptual threshold is measured on 0
      100mm scales positioned below adult and child figures. This report presents three
      studies that evaluate the psychometric properties of this variable. Study
      1explored its independence from BMI and body image in factor analyses with
      diverse samples (Ukrainian, Mexican and US Black, White, and Hispanic). Study 2
      was a replication of this factor structure, and Study 3 investigated the
      reliability of the perceptual threshold using classical test (CT) and
      generalizability methods (GT). In Studies 1 and 2, two factors were identified
      (Perceptual Threshold for Overweight and Body Image/BMI) with almost identical
      factor structures in six analyses. In Study 3 the CT and GT procedures
      demonstrated adequate reliability. These results indicate that the psychometric
      properties of the perceptual threshold are sound, and support its use in
      exploring the social transmission of weight and evaluating obesity prevention and
      intervention programs.

PMID- 22664398
TI  - Case-control study of disturbed eating behaviors and related psychographic
      characteristics in young adults with and without diet-related chronic health
      conditions.
AB  - Young adults with diet-related chronic health conditions (DRCHCs; i.e., type 1
      diabetes, celiac disease, cystic fibrosis, inflammatory bowel diseases, irritable
      bowel syndrome) face challenges complying with dietary restrictions required to
      effectively manage their health condition. These restrictions could put them at
      risk for disturbed eating. The purpose of this study was to determine if young
      adults with and without DRCHCs differed with regard to disturbed eating behaviors
      and related psychographics characteristics (i.e., body image attributes, mental
      disorders, intrapersonal characteristics and sociocultural environment [i.e.,
      media and family]). Each DRCHC participant (cases=166) was matched to 4 healthy
      participants (controls=664) based on gender and BMI (+/-0.50 BMI units).
      Conditional logistic regression analyses indicate cases were twice as likely to
      have been diagnosed by a healthcare provider with an eating disorder (p=0.08,
      OR=1.99, CI(90) [1.03-3.83]). Cases were significantly more likely to use
      Inappropriate Compensatory Behaviors to manage their weight, i.e., excessive
      exercise (p=0.04, OR=1.41, CI(95) [1.02-1.94]) and misuse medication (p=0.04,
      OR=1.14, CI(95) [1.00-1.29]) than controls. Depression and anxiety were
      significantly higher, and health status was significantly poorer in cases
      compared with controls. DRCHC participants were less likely to report feeling
      body image pressures from the media, placed a greater value on their health, used
      social diversion, and recalled a greater emphasis being placed on their mothers'
      weights and mealtimes being less structured than control participants. Findings
      indicate that nutrition and other healthcare professionals should incorporate
      screening DRCHC patients for disturbed eating behaviors and eating disorders in
      their standards of care.

PMID- 22664397
TI  - Night eating is associated with emotional and external eating in college
      students.
AB  - The night eating syndrome (NES) consists of evening hyperphagia and/or nocturnal
      eating and has been associated with depressed mood that worsens in the evening.
      However, it is not consistently related to elevated BMI. The present study was
      conducted to examine whether a relationship exists between NES and emotional,
      external, and restrained eating. BMI and sleep quality were also obtained. A
      sample of 246 students completed the Night Eating Diagnostic Questionnaire
      (NEDQ), Night Eating Syndrome History and Inventory (NESHI), Sleep Quality Index
      (SQI), and Dutch Eating Behavior Questionnaire (DEBQ), containing subscales for
      emotional, external, and restrained eating. They also provided demographic
      information, including height and weight. Participants were grouped by severity
      of NES features using the NEDQ and NESHI: normal, mild night eater, moderate
      night eater, and full night eater syndrome. MANOVA was used to compare DEBQ
      subscores for the groups; those in the full syndrome category had significantly
      higher emotional eating scores and external eating scores than those in the
      normal and mild categories. There was no difference in restrained eating between
      the normal and full syndrome groups. Those with moderate and full syndrome NES
      symptoms also reported significantly lower sleep quality. No significant
      relationship was found between NES and BMI. The results show that NES is
      associated with more eating in response to negative mood and in response to food
      cues.

PMID- 22664399
TI  - Body esteem and eating disorder symptomatology: the mediating role of appearance
      motivated exercise in a non-clinical adult female sample.
AB  - OBJECTIVES: Low body esteem poses a risk for the development of eating disorder
      symptomatology. Appearance-motivated exercise, as opposed to health-motivated
      exercise, has been associated with both low body esteem and eating disorder
      symptomatology. The aim of this study was to investigate the mediating role of
      appearance-motivated exercise in the link between body esteem and eating disorder
      symptomatology. METHOD: Female fitness club members (N=81) reported their body
      esteem, eating disorder symptomatology and exercise motives. RESULTS: Appearance
      motivated exercise partially mediated the link between low body esteem and eating
      disorder symptomatology. In contrast, health-motivated exercise was unrelated to
      both body esteem and eating disorder symptomatology. CONCLUSION: Results indicate
      that the motives underlying exercise in response to low body esteem have
      differential consequences for the potential development of eating disorders,
      signifying the clinical relevance of considering motives behind exercise.

PMID- 22664396
TI  - Physical activity as a moderator of the association between anxiety sensitivity
      and binge eating.
AB  - Individuals with elevated anxiety sensitivity (AS; i.e., fear of somatic arousal)
      may binge eat to reduce emotional distress. Because physical activity reduces
      stress reactivity, we predicted that: (1) the relation between AS and binge
      eating would be moderated by physical activity and (2) coping motives for eating
      would mediate the association between AS and binge eating such that the relation
      would be stronger for those low in physical activity. Participants (N=167)
      completed online self-report measures. Regression analyses revealed that moderate
      intensity physical activity (MPA) moderated the relation between AS and binge
      eating such that AS was not related to binge eating among those who frequently
      engaged in MPA but was related to binge eating among those who did not report
      engaging in MPA. Vigorous-intensity physical activity (VPA) moderated in the
      opposite direction such that the relation between AS and binge eating was
      significant among persons reporting high levels of VPA but less strong among
      persons reporting low levels of VPA. The mediation model was also significant,
      but was not moderated by MPA or VPA. Theoretical and clinical implications are
      discussed.

PMID- 22664400
TI  - Adding thin-ideal internalization and impulsiveness to the cognitive-behavioral
      model of bulimic symptoms.
AB  - This study evaluated the cognitive-behavioral (CB) model of bulimia nervosa and
      an extension that included two additional maintaining factors - thin-ideal
      internalization and impulsiveness - in 327 undergraduate women. Participants
      completed measures of demographics, self-esteem, concern about shape and weight,
      dieting, bulimic symptoms, thin-ideal internalization, and impulsiveness. Both
      the original CB model and the extended model provided good fits to the data.
      Although structural equation modeling analyses suggested that the original CB
      model was most parsimonious, hierarchical regression analyses indicated that the
      additional variables accounted for significantly more variance. Additional
      analyses showed that the model fit could be improved by adding a path from
      concern about shape and weight, and deleting the path from dieting, to bulimic
      symptoms. Expanding upon the factors considered in the model may better capture
      the scope of variables maintaining bulimic symptoms in young women with a range
      of severity of bulimic symptoms.

PMID- 22664401
TI  - Multidimensional perfectionism, depression and relational health in women with
      eating disturbances.
AB  - OBJECTIVE: This study investigated multidimensional perfectionism, depression,
      and relational health and quality across varying severities of eating disorders.
      The Questionnaire for Eating Disorder Diagnoses (Mintz, O'Halloran, Mulholland, &
      Schneider, 1997) was used to distinguish clinical, subclinical, and asymptomatic
      groupings. METHOD: The sample included 212 women recruited from a university and
      an eating disorder treatment center. RESULTS: Results indicated significant
      differences across all the three groups on perfectionistic discrepancy. All three
      groups also differed on their level of depressive mood. However, there were no
      significant group differences on relational health and quality. DISCUSSION: This
      study contributes to the understanding of intrapersonal and interpersonal
      correlates of eating disorders and subclinical eating disturbances. This
      understanding allows for better identification of vulnerability to eating
      disorders and offers the potential to design more specialized and effective
      treatments.

PMID- 22664402
TI  - Peer influence on youth's snack purchases: a laboratory analog of convenience
      store shopping.
AB  - OBJECTIVE: This paper reports the results of two experiments using a laboratory
      analog to examine the influence of taxes and subsidies on youth's snack food
      purchases when alone (Experiment 1) and when in the presence of a same-gender
      peer (Experiment 2). METHOD: Adolescents (12-14-years-old) completed a purchasing
      task, during which prices of snack foods were manipulated, either alone in
      Experiment 1 (N=37) or in the presence of an unfamiliar peer in Experiment 2
      (N=52). RESULTS: In both experiments, purchases of unhealthy snacks decreased and
      purchases of healthy snacks increased when the price of unhealthy snacks were
      taxed (increased). In Experiment 1 (alone), participants did not purchase more
      healthy snacks when the price of these snacks were subsidized (decreased).
      However, in Experiment 2 (when participants were in the presence of a peer),
      participants purchased more healthy snacks when these snacks were subsidized.
      CONCLUSION: Taxes and subsidies affect adolescents' snack purchasing, as does the
      presence of peers. The results of this study highlight factors that influence
      healthy and unhealthy snack purchasing behavior in young adolescents.

PMID- 22664403
TI  - The role of body image flexibility in the relationship between disordered eating
      cognitions and disordered eating symptoms among non-clinical college students.
AB  - OBJECTIVE: A growing body of evidence suggests that rigid and inflexible
      regulation and coping are at the core of psychopathology, including disordered
      eating (DE) problems. Employing two cross-sectional studies, the present paper
      investigated whether body image flexibility (BIF), a specific type of
      psychological flexibility, mediates the relations between DE cognitions and
      overall DE pathology. METHOD: Ethnically diverse non-clinical college
      undergraduates (Study 1 N=208; Study 2 N=178) completed an anonymous online
      survey. RESULTS: BIF was found to partially mediate the relationship between DE
      cognitions and overall DE pathology after controlling for gender and body mass
      index (BMI). DISCUSSION: Our findings suggest that the link between DE cognitions
      and overall DE pathology is established in part through an inflexible and
      avoidant coping style specific to negative body image. Clinical implications
      include targeting BIF as a mechanism of change and treating DE pathology with
      acceptance- and mindfulness-based behavioral interventions.

PMID- 22664404
TI  - Examining the effects of remote-video confederates on young women's food intake.
AB  - One's decisions about eating are at times, largely based on the observations of
      other people's eating behavior. Previous studies have shown that modeling of
      eating is a robust effect. The current research examined the impact of a video
      remote confederate on young women's food intake. Experiment 1 examined the effect
      of an eating or non-eating video confederate. Participants (N=77 female
      undergraduate students, M age=20.29) were exposed to a same-sex video confederate
      (i.e., a 25 year old woman) who was modeling eating (i.e., 4 winegums; pastille
      type sweets) or not eating (i.e. no food visible). Results indicated that
      participants exposed to the eating confederate did not eat more than participants
      exposed to the non-eating confederate. Experiment 2 was conducted to address some
      of the limitations of Experiment 1. In this experiment, participants (N=51, M
      age=20.43) were exposed to one of three intake conditions: No-eating (i.e. food
      visible but not consumed), Small portion-size condition (i.e., 8 M&Ms) or Large
      portion-size condition (i.e., 20 M&Ms). The same video confederate as in
      Experiment 1 modeled these three conditions. Results indicated that participants
      did not adjust their intake to that of a video model. The current findings
      provide preliminary evidence for the assumption that modeling only exists if
      people have clear indications about how much others have consumed in the same
      context (as was the case in previous modeling studies). Future research is needed
      to further examine this proposition.

PMID- 22664405
TI  - Food cravings in food addiction: the distinct role of positive reinforcement.
AB  - Craving for a particular substance is an essential characteristic of addictive
      behavior. Increasing evidence suggests that food cravings and excessive food
      consumption could similarly be due to addictive processes. Recently, the Yale
      Food Addiction Scale (YFAS) was introduced for identifying individuals with
      addictive eating patterns. We conducted an online study (n=616, 75.8% female) in
      which participants filled out the YFAS and the Food Cravings Questionnaire-Trait
      (FCQ-T). Participants diagnosed as being addicted to food using the YFAS had
      higher scores on all food craving subscales except for anticipation of positive
      reinforcement that may result from eating. In a subsequent regression analysis,
      all food craving subscales positively predicted food addiction symptoms while
      positive reinforcement negatively predicted food addiction symptoms. Similar to
      other addictive behaviors, results indicate that individuals with addictive
      eating patterns experience more food cravings, but concurrently do not expect a
      positive reinforcement through eating.

PMID- 22664406
TI  - Plasma, salivary, and urinary oxytocin in anorexia nervosa: a pilot study.
AB  - Although oxytocin (OT) has the potential to be an informative biomarker of social
      functioning in patients with eating disorders, the burden of invasive blood draws
      or lumbar punctures limits OT study. Salivary and urinary OT measurements may be
      advantageous, as they require less invasive sampling techniques which could be
      conducted in a wider variety of settings. Yet, the degree to which the
      concentration of OT in these fluids is correlated with blood levels is uncertain,
      as is the impact of vomiting on salivary secretion of OT. Therefore, we compared
      contemporaneously sampled OT concentration in blood, saliva, and urine from
      twenty women acutely ill with anorexia nervosa. Salivary OT was positively
      correlated with plasma OT in patients with no history of self-induced vomiting
      (r=0.89), but correlation was lower in those with recent history of self-induced
      vomiting (r=0.42). Urinary and plasma OT were not well-correlated(r=0.13),
      suggesting preliminarily that collection of plasma OT remains the method of
      choice. Self-induced vomiting in eating disorders may limit the applicability of
      salivary sampling for OT.

PMID- 22664409
TI  - Confirmatory factor analysis of the Children's Eating Behaviour Questionnaire in
      a low-income sample.
AB  - Although pediatric obesity is prevalent in low-income and African American and
      Hispanic communities, validated measures of child eating habits are lacking for
      these communities. In this study, confirmatory factor analysis was used to
      validate the hypothesized 7-factor structure of the Children's Eating Behaviour
      Questionnaire (CEBQ). The sample included 229 parent-child pairs, the majority
      low-income and Hispanic (57%) or African American (25%). The a priori structure
      of the CEBQ failed to replicate. Exploratory factor analysis revealed 3 factors:
      Disinhibition, Food interest, and Undereating, none predicting child BMI.
      Although limited by the observational, cross-sectional design, results indicate
      that the CEBQ needs additional study.

PMID- 22664408
TI  - An interactional test of the reformulated helplessness theory of depression in
      women receiving clinical treatment for eating disorders.
AB  - The study tested the Reformulated Helplessness model that individuals who show
      combined internal locus of control, high stability and high globality
      attributions for negative life events are prone to depression. Thirty-six women
      (M=29 years-8 months of age) receiving clinical treatment for eating disorders
      completed: the Attribution Style Questionnaire, the Beck Depression Inventory,
      and the Stirling Eating Disorder Scales. An HRA yielded a three-way interaction
      among the attributional dimensions on depressive symptoms. Plotting of the slopes
      showed that the attribution of negative life events to the combination of
      internal locus of control, high stability, and a high globality, was associated
      with the optimal level of depressive symptoms. The findings supported the
      Reformulated Helplessness as a model of depression.

PMID- 22664407
TI  - Transcultural adaptation of the Night Eating Questionnaire (NEQ) for its use in
      the Spanish population.
AB  - BACKGROUND: Establishing valid and reliable methods of assessing night eating
      symptoms is an important goal to maximize identification and treatment of the
      night eating syndrome (NES). The 14-item Night Eating Questionnaire (NEQ) is the
      only published and validated assessment instrument but is not yet adapted to
      Spanish. METHODS: We examined the factor structure, internal consistency and
      validity of the NEQ in Spanish. The study had 4 phases: a) translation from
      English to Spanish; b) back-translation from Spanish to English, c)
      administration of translated version to a Spanish sample, and d) a re-test in 36
      participants two weeks later. Reliability, stability, and scale structure were
      evaluated by Cronbach's alpha, test-re-test, and factor analysis, respectively.
      Divergent validity was assessed by correlation with the Spanish versions of the
      State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory (BDI-II).
      RESULTS: Two-hundred forty-four individuals (181 f; BMI 34.3+/-10 kg/m(2); age
      40.5+/-15 y) completed the questionnaire. The mean NEQ score was 12.5+/-7. The
      Cronbach's alpha coefficient for the total score was 0.79, the intraclass
      correlation was 0.85, and the factor analysis yielded a similar four factor
      solution as the original scale. Correlation for the test-re-test total score was
      0.86. Total NEQ score was significantly correlated with the BDI-II (r=0.48
      p<0.001), but this correlation was not significant during the test-re-test
      (r=0.28, p=0.10) or with STAI at either time point (0.05, p=0.40; r=0.07, p=0.69,
      respectively). CONCLUSIONS: The Spanish version of the NEQ demonstrated adequate
      internal consistency for the majority of domains and excellent reproducibility.
      There was divergent validity with anxiety and a relationship between night eating
      and depression. These results suggest that the Spanish-version of the NEQ is an
      instrument that is valid for use in clinical research.

PMID- 22664410
TI  - One-year change in energy and macronutrient intakes of overweight and obese inner
      city African American children: effect of community-based Taking Action Together
      type 2 diabetes prevention program.
AB  - Taking Action Together (TAT) was a controlled community-based intervention
      protocol developed to reduce risk of T2DM among low-income, high BMI, 9-10 year
      old African American children. A secondary hypothesis of this study was that
      there would be greater improvements in the treatment group in dietary intakes and
      physical activity. To evaluate the primary study objectives, multiple linear
      regression models were employed, with 1 year change in dietary variables as
      dependent variables. Intervention group status was the independent variable of
      interest and BMIz was included as a covariate in all analyses to adjust for group
      differences in baseline obesity status of the children. The findings from this
      analysis suggest that 1 year change in dietary intakes in boys was associated
      with group intervention status, with boys in the treatment group reducing their
      intakes of energy and fat to a significantly greater extent than boys in the
      control group. Differences in energy intakes were not significant, however, for
      girls. Based on the differences in gender response to our comprehensive TAT
      intervention, we conclude that interventions designed for and delivered only to
      African American girls might be more successful than those delivered in mixed
      gender settings.

PMID- 22664411
TI  - Guilty pleasures II: restrained eaters' implicit preferences for high, moderate
      and low-caloric food.
AB  - In a previous study, restrained eaters showed stronger implicit preferences for
      high-caloric food compared to unrestrained eaters. Caloric density and
      palatability are however almost always intertwined, and it was never tested
      whether this high-calorie food preference of restrained eaters follows from the
      energy density or the palatability of high-calorie foods. Here, it was examined
      whether restrained eaters may hold stronger implicit preferences than
      unrestrained eaters for palatable food in general, irrespective of caloric
      density. Participants were randomly assigned to one of three conditions: Using
      two unipolar SCIATs positive and negative implicit associations were measured
      with palatable food of either high, moderate, or low caloric density. Results
      showed a strong effect of dietary restraint on implicit food preferences
      independently of caloric density, indicating stronger implicit preferences for
      all types of palatable food with increased dietary restraint. With respect to
      negative implicit associations, participants showed stronger negative implicit
      associations with high-calorie food than with moderate-calorie or low-calorie
      food, regardless of dietary restraint. Thus, restrained eaters show enhanced
      implicit preferences, not only for high caloric food, but for palatable food in
      general compared to unrestrained eaters.

PMID- 22664412
TI  - Validation of an online questionnaire measure of the relative reinforcing value
      of food.
AB  - Laboratory methods and questionnaires to assess the relative reinforcing value of
      food (RRV-F) have been developed, but this is the first study to validate an
      online questionnaire measure of the RRV-F. Participants (281 college students)
      completed an online survey assessing demographic variables, food preferences, and
      the RRV-F. A subsample (n=21) also completed a laboratory food choice session.
      The online RRV-F instrument showed strong predictive validity for laboratory food
      choice behavior, convergent validity with overweight status, and discriminant
      validity with unrelated constructs (age, gender, height). Results suggest that
      online methodology is appropriate for assessing the RRV-F in a manner that is
      cost-effective, time-efficient, affords greater anonymity, and enables
      recruitment from larger samples over a broader geographic region.

PMID- 22664413
TI  - Campus programming for National Eating Disorders Awareness Week: an investigation
      of stigma, help-seeking, and resource knowledge.
AB  - This study investigated the effectiveness of on-campus programming for National
      Eating Disorders Awareness Week (NEDAwareness Week). The aim was to investigate
      the impact of a campus-wide, week-long series of psycho-educational and awareness
      programs designed for NEDAwareness Week. The study sought to determine whether
      students who attended programming, when compared to students who had not attended
      campus programming, would report (a) higher levels of help-seeking behaviors, (b)
      lower levels of stigma, and (c) greater knowledge of available on-campus
      resources for students experiencing body image issues and eating disorders.
      Results indicated that students who attended one-time intervention programs knew
      more about available on-campus resources for students experiencing body image
      issues and eating disorders than students who did not attend programming. The
      findings suggest that students who attended one-time intervention programs for
      NEDAwareness Week had higher levels of factual knowledge of available campus
      resources for body image issues and eating disordered behaviors than students who
      did not attend campus programming for NEDAwareness Week.

PMID- 22664414
TI  - Alcohol consumption as a function of dietary restraint and the menstrual cycle in
      moderate/heavy ("at-risk") female drinkers.
AB  - Previous research suggests that women who report dietary restraint tend to
      consume alcohol in greater quantities, however most studies use retrospective
      data collection, which is often unreliable, and no studies have accounted for
      this relationship with respect to potential changes in alcohol consumption across
      the menstrual cycle. Therefore, the present study investigated the relationship
      between prospectively monitored drinking patterns and dietary restraint across
      the menstrual cycle among females from the general population whose drinking
      level (7-20 drinks/week) places them at-risk for developing alcohol use
      disorders. Restrained eaters (RES; N=51) and unrestrained eaters (UN-RES; N=55),
      per the cognitive restraint scale scores from the Three-Factor Eating
      Questionnaire, provided prospective ratings measuring mood, alcohol consumption,
      and consequences of alcohol use across one full menstrual cycle. Dysphoric mood
      increased during the late luteal and menstrual phases in both groups. Although
      overall the RES group did not drink more than the UN-RES group, the RES group
      drank less than the UN-RES group during the follicular phase, suggesting that
      among RES women alcohol consumption may be modulated by hormonal fluctuations
      across the menstrual cycle. The differences between the present findings and
      previous research may be due to the cohorts sampled; the majority of previous
      studies sampled college students, where binge drinking and dietary restraint are
      more common, whereas this study sampled the general population. Future research
      should replicate prior studies in a college-aged population using the current
      design of prospective data collection for greater accuracy of self-reported
      alcohol consumption.

PMID- 22664415
TI  - Positive cognitive coping strategies and binge eating in college women.
AB  - The current study explored whether specific cognitive coping strategies moderated
      the relation between global eating disorder symptomatology and binge eating
      frequency. Global eating disorder symptomatology and cognitive coping strategies
      (i.e., self-blame, acceptance, rumination, positive refocusing, refocus on
      planning, positive reappraisal, putting into perspective, catastrophizing, and
      other-blame) were evaluated in a sample of women who reported engaging in binge
      eating in the absence of compensatory behaviors (N=419). Moderation analyses
      indicated that most positive cognitive coping strategies were associated with
      reduced binge eating frequency; however, there was no such buffering effect among
      individuals who reported engaging in acceptance, or in negative coping
      strategies. These results suggest that focusing on specific positive cognitive
      coping skills might be an effective approach to decreasing binge eating
      frequency, although additional experimental research is needed.

PMID- 22664416
TI  - Effects of cumulative smoking exposure and duration of smoking cessation on
      carotid artery structure.
AB  - BACKGROUND: While prior epidemiological studies have examined the association
      between cigarette smoking and carotid atherosclerosis, few studies have evaluated
      the association of both cumulative smoking exposure and the duration of smoking
      cessation with carotid artery structure. METHODS AND RESULTS: The study
      population consisted of 2,503 community-dwelling Korean males aged 50 years and
      older. Common carotid artery intima-media thickness (CCA-IMT), carotid plaque,
      and the internal diameter of the common carotid artery (CCA-diameter) were
      determined by high-resolution B-mode ultrasonography. Data on the characteristics
      of the subjects, including smoking status, pack-years of smoking, and years since
      quitting smoking, were collected using a standardized questionnaire. The current
      smokers had significantly greater CCA-IMT and CCA-diameter and a significantly
      higher risk of carotid plaque than did the subjects who had never smoked
      (P=0.009, <0.001, and 0.036, respectively). Dose-response relationships between
      pack-years and CCA-IMT and CCA-diameter were found among the current smokers
      (P=0.001 and <0.001, respectively); however, no significant association between
      pack-years and the carotid artery parameters was observed among the former
      smokers. For the former smokers, CCA-IMT and CCA-diameter tended to decrease with
      increasing years since quitting smoking (P=0.009 and 0.012, respectively),
      whereas no significant association with carotid plaque was found. CONCLUSIONS:
      Cumulative smoking exposure in current smokers and the duration of smoking
      cessation in former smokers are significant risk factors for carotid
      atherosclerosis.

PMID- 22664418
TI  - Phase analysis using gated myocardial perfusion single-photon emission computed
      tomography imaging for evaluating cardiac dyssynchrony.

PMID- 22664417
TI  - Diagnostic value of left ventricular dyssynchrony after exercise and at rest in
      the detection of multivessel coronary artery disease on single-photon emission
      computed tomography.
AB  - BACKGROUND: Although stress-induced left ventricular (LV) wall motion abnormality
      is a well-known marker for extensive coronary artery disease (CAD), no study has
      yet analyzed whether phase analysis of exercise-induced LV mechanical
      dyssynchrony may have enhanced diagnostic value over conventional perfusion
      analysis in the detection of multivessel CAD. METHODS AND RESULTS: A total of 278
      patients with suspected or confirmed CAD underwent both exercise stress (99m)Tc
      sestamibi gated single-photon emission computed tomography and coronary
      angiography. LV mechanical dyssynchrony was evaluated using the SyncTool to
      obtain the phase SD and histogram bandwidth. In the detection of 128 patients
      with multivessel CAD, a summed stress score (SSS) of >=9 showed a sensitivity of
      84% and a specificity of 53%, while an increase in phase SD of >=4.4 degrees  and
      a bandwidth of >=14 degrees  after exercise had sensitivities of 74% and 68%, and
      specificities of 84% and 91%, respectively. On multivariate analysis the
      combination of post-stress increases in phase SD, histogram bandwidth, transient
      ischemic dilation (TID) ratio and SSS best identified multivessel CAD
      (sensitivity 77%, specificity 88%, chi(2)=181.8), compared with TID ratio and SSS
      only (sensitivity 70%, specificity 76%, chi(2)=68.9). CONCLUSIONS: The addition
      of phase analysis to evaluate exercise-induced LV mechanical dyssynchrony on
      conventional perfusion analysis enabled better identification of patients with
      multivessel CAD.

PMID- 22664419
TI  - Correlation between populations of Rhodnius and presence of palm trees as risk
      factors for the emergence of Chagas disease in Amazon region, Brazil.
AB  - Among the states that comprise the legally defined Amazon region of Brazil, Para
      has presented the highest occurrences of acute cases of Chagas disease over the
      last two decades. These cases have been attributed to consumption of fruits from
      native palm trees. In surveys in rural and wild areas of the municipality of
      Oriximina, Para, triatomine fauna, their main ecotopes and the infection rate due
      to Trypanosoma cruzi were identified using active and passive search methods:
      manual capture and Noireau traps, respectively. A total of 582 ecotopes were
      surveyed using 1496 Noireau traps. Out of 442 specimens collected, 289 were
      identified as Rhodnius robustus and 153 as Rhodnius pictipes. The infection rate
      caused by T. cruzi was 17.4%. The food sources of the triatomines were found to
      be birds, hemolymph, horses, and rodents. The association between R. robustus and
      inaja palm trees (Attalea marita), which are abundant in rural areas, was
      confirmed. On the other hand, R. pictipes is found in several palm tree species,
      such as inaja (A. marita), mucaja (Acrocomia aculeata), murumuru (Astrocaryum
      murumuru) and pataua (Oenocarpus bataua), and in bromeliads in wild areas. These
      occurrences of triatomine species in regions with or without T. cruzi infection,
      in the vicinity of the main settlement of the municipality, suggest that there is
      a need for entomological and epidemiological surveillance in this region.

PMID- 22664420
TI  - Entamoeba moshkovskii perspectives of a new agent to be considered in the
      diagnosis of amebiasis.
AB  - During the last decade Entamoeba moshkovskii has become relevant given its
      capacity to infect humans, especially when considering that it is morphologically
      indistinguishable from E. histolytica. For a long time, E. moshkovskii was
      considered as a free living amoeba, but in the last decade it has been
      demonstrated that E. moshkovskii can infect humans and can be found more
      frequently in regions where amebiasis shows high prevalence values, becoming a
      challenge to differentiate it from the E. histolytica/E. dispar complex. Recently
      there have been studies that raise the possibility that E. moshkovskii could be a
      pathogenic species, as there are reports in different countries that associated
      this infection with gastrointestinal symptoms even though others have described
      it as a non pathogenic species. For this reasons, both clinical and
      epidemiological studies are required.

PMID- 22664421
TI  - Stimulation of molt by RNA interference of the molt-inhibiting hormone in the
      crayfish Cherax quadricarinatus.
AB  - In crustaceans, molting is known to be under the control of neuropeptide hormones
      synthesized and secreted from the eyestalk ganglia. While the role of molt
      inhibiting hormone (MIH) in regulating molting has been described in several
      species using classical methods, an in vivo specific MIH targeted manipulation
      has not been described yet. In the present study, an MIH cDNA was isolated and
      sequenced from the eyestalk ganglia of the Australian freshwater red claw
      crayfish Cherax quadricarinatus (Cq) by 5' and 3' RACE. We analyzed the putative
      Cq-MIH based on sequence homology, a three dimensional structure model and
      transcript's tissue specificity. We further examined the involvement of Cq-MIH in
      the control of molt in the crayfish through RNAi by in vivo injections of Cq-MIH
      double-stranded RNA, which resulted in, similarly to eyestalk ablation,
      acceleration of molt cycles. This acceleration was reflected by a significant
      reduction (up to 32%) in molt interval and an increased rate in molt
      mineralization index (MMI), which correlated with the induction of ecdysteroid
      hormones compared to control. Altogether, this study provides a proof of function
      for the involvement of the Cq-MIH gene in molt regulation in the crayfish.

PMID- 22664422
TI  - Tissue-specific distribution of fatty acids, polychlorinated biphenyls and
      polybrominated diphenyl ethers in fish from Taihu Lake, China, and the benefit
      risk assessment of their co-ingestion.
AB  - The fish tissues from four species collected from Taihu Lake, China, were
      analyzed including dorsal, ventral, and tail muscles, heart, liver, and kidney.
      The highest and lowest concentrations of fatty acids were respectively observed
      in livers and muscles. There were significant intraspecies and interspecies
      differences in the compositions of most fatty acids among muscle, heart, liver,
      and kidney. All the tissues were generally beneficial for consumption considering
      fatty acids. People mainly consume the muscle. Hence, the benefits from two
      polyunsaturated fatty acids, i.e., eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), and risks from PCBs and PBDEs via fish consumption
      were evaluated by calculating the benefit-risk quotient (BFQ) for the intake of
      fish muscle containing EPA+DHA vs. PCBs or PBDEs. The BFQ values considering
      carcinogenic and noncarcinogenic effects for PCBs were ~3000 and 10 times higher
      than those of PBDEs via fish consumption to achieve the recommended EPA+DHA
      intake of 250 mg d(-1), respectively. The results also suggested that the risk
      consuming the dorsal muscle was generally lower than the ventral and tail
      muscles.

PMID- 22664423
TI  - Salidroside protects PC12 cells from MPP+-induced apoptosis via activation of the
      PI3K/Akt pathway.
AB  - Oxidative stress plays an important role in the pathogenesis of Parkinson's
      disease (PD). Salidroside (SAL), a phenylpropanoid glycoside isolated from
      Rhodiola rosea L., can exert potent antioxidant properties. In this study, we
      investigated the protective effects, and the possible mechanism of action, of SAL
      against 1-methyl-4-phenylpyridinium (MPP(+))-induced cell damage in rat adrenal
      pheochromocytoma PC12 cells. Pretreatment of PC12 cells with SAL significantly
      reduced the ability of MPP(+) to induce apoptosis in a dose and time-dependent
      manner. SAL significantly and dose-dependently inhibited MPP(+)-induced chromatin
      condensation and MPP(+)-induced release of lactate dehydrogenase by PC12 cells.
      SAL enhanced Akt phosphorylation in PC12 cells, and the protective effects of SAL
      against MPP(+)-induced apoptosis were abolished by LY294002, a specific inhibitor
      of phosphatidylinositol 3-kinase (PI3K) phosphorylation. These findings suggest
      that SAL prevents MPP(+)-induced apoptosis in PC12 cells, at least in part
      through activation of the PI3K/Akt pathway.

PMID- 22664424
TI  - Structural influence of isothiocyanates on expression of cytochrome P450, phase
      II enzymes, and activation of Nrf2 in primary rat hepatocytes.
AB  - Primary cultures of rat hepatocytes were used to investigate whether and how
      eight isothiocynates (ITCs) with different chemical structures (the aromatic
      benzyl, 4-hydroxybenzyl, phenethyl isothiocyanates and the aliphatic allyl,
      napin, iberin, raphasatin isothiocyanates and sulforaphane) derived from
      hydrolyzed glucosinolates, were able to modulate cytochrome P450 (CYP) and
      antioxidant/detoxifying enzymes and to activate the Nrf2 transcription factor.
      The aromatic ITCs at 40 MUM markedly increased the transcription of CYP1A1 and
      1A2 mRNA and increased the associated ethoxyresorufin O-deethylase (EROD)
      activity after 24 h of treatment. By contrast, the aliphatic ITCs (40 MUM)
      decreased CYP1A1 and 1A2 transcription, together with the corresponding EROD
      activity. The same treatment also caused a striking and similar transcriptional
      repression of CYP3A2, and the corresponding benzyloxyquinoline debenzylase
      activity in response to all the ITCs tested. In the same culture conditions, most
      of the antioxidant/detoxifying enzymes were significantly up-regulated by 40MUM
      ITCs. In particular, NAD(P)H:quinone oxidoreductase and heme oxygenase-1 were
      induced, although to different levels, at transcriptional, protein and/or
      activity levels by all the ITCs. However, glutathione S-transferase activity was
      not induced by the allyl, benzyl, and 4-hydroxybenzyl ITCs, glutathione reductase
      activity was not induced by benzyl, and 4-hydroxybenzyl ITCs and catalase
      activity was not induced by allyl ITC. As for the Nrf2 transcription factor, a
      partial translocation of its protein from the cytosol to the nucleus was revealed
      by immunoblotting after 1h of treatment for all the ITCs tested. The ability of
      ITCs to induce the antioxidant and phase II enzymes did not appear to be affected
      by their hydrophilicity or other structural factors. Taken together, these
      results show that these ITCs are effective inducers of ARE/Nrf2-regulated
      antioxidant/detoxifying genes and have the potential to inhibit, at least in rat
      liver, the bioactivation of carcinogens dependent on CYP3A2 catalysis.

PMID- 22664425
TI  - Monitoring quality of HIV testing at point of care facilities in India.

PMID- 22664426
TI  - Laboratory quality management system: road to accreditation and beyond.
AB  - This review attempts to clarify the concepts of Laboratory Quality Management
      System (Lab QMS) for a medical testing and diagnostic laboratory in a holistic
      way and hopes to expand the horizon beyond quality control (QC) and quality
      assurance. It provides an insight on accreditation bodies and highlights a
      glimpse of existing laboratory practices but essentially it takes the reader
      through the journey of accreditation and during the course of reading and
      understanding this document, prepares the laboratory for the same. Some of the
      areas which have not been highlighted previously include: requirement for
      accreditation consultants, laboratory infrastructure and scope, applying for
      accreditation, document preparation. This section is well supported with
      practical illustrations and necessary tables and exhaustive details like
      preparation of a standard operating procedure and a quality manual. Concept of
      training and privileging of staff has been clarified and a few of the QC
      exercises have been dealt with in a novel way. Finally, a practical advice for
      facing an actual third party assessment and caution needed to prevent post
      assessment pitfalls has been dealt with.

PMID- 22664427
TI  - Pathogenomics of uropathogenic Escherichia coli.
AB  - Subset of faecal E. coli that can enter, colonize urinary tract and cause
      infection are known as uropathogenic E. coli (UPEC). UPEC strains act as
      opportunistic intracellular pathogens taking advantage of host susceptibility
      using a diverse array of virulence factors. Presence of specific virulence
      associated genes on genomic/pathogenicity islands and involvement of horizontal
      gene transfer appears to account for evolution and diversity of UPEC. Recent
      success in large-scale genome sequencing and comparative genomics has helped in
      unravelling UPEC pathogenomics. Here we review recent findings regarding
      virulence characteristics of UPEC and mechanisms involved in pathogenesis of
      urinary tract infection.

PMID- 22664428
TI  - Serum hepatitis B surface antigen levels correlate with high serum HBV DNA levels
      in patients with chronic hepatitis B: a cross-sectional study.
AB  - PURPOSE: The hallmark of chronic hepatitis B (CHB) infection is the presence of
      hepatitis B surface antigen (HBsAg) positivity for at least 6 months. Recently,
      serum levels of HBsAg have been compared with serum HBV DNA as a surrogate marker
      to monitor CHB patients. However, data correlating these two markers are scarce.
      Hence, the present study was done to correlate HBV DNA with HBsAg in CHB
      patients. MATERIALS AND METHODS: Consecutive patients of CHB were included. HBV
      DNA was measured by real-time polymerase chain reaction (PCR). Serum HBsAg was
      measured by Architect HBsAg. RESULTS: Of the 198 patients enrolled, 166 fulfilled
      the inclusion criteria (mean age 43 +/- 14 years, 87% males) and the median HBV
      DNA was 1.7 * 10 3 (range 6.0-1.1 * 10 8 ) IU/ml. Median HBsAg was 8.7 * 10 3
      (range 5.0-3.2 * 10 5) IU/ml. Overall correlation between HBV DNA and HBsAg was
      weak but significant (Spearman rho = 0.443, P < 0.01). Correlation in HBe antigen
      positive group was better (rho = 0.402, P < 0.01) in comparison to HBe antigen
      negative group (rho = 0.193 P = 0.05). Good correlation existed in treatment
      naive group (rho = 0.538, P < 0.01) .Correlation was regardless of normal or
      raised alanine transaminase (ALT). Eighty (48%) patients had high HBV DNA (>=
      2000 IU/ml). Correlation in high DNA group was significant (P < 0.01). The best
      cut-off of HBsAg for diagnosing high DNA is 3.36 *10 3 IU/ml. CONCLUSIONS: Serum
      HBsAg correlates with HBV DNA in CHB patients, especially in high serum HBV DNA,
      HBe antigen-positive and treatment-naive group. HBsAg levels can be used for
      predicting high serum HBV DNA levels.

PMID- 22664429
TI  - Prevalence of influenza virus among the paediatric population in Mumbai during
      2007-2009.
AB  - PURPOSE: Influenza has a major impact on public heath, annually affecting 15-20%
      of the global population. Information on the activity of influenza virus in
      Mumbai is limited. The present study was carried out to determine the prevalence
      of influenza viruses causing acute respiratory infections in children by
      molecular methods. OBJECTIVE: To study the prevalence of influenza viruses among
      the paediatric population in Mumbai by real-time reverse-transcriptase polymerase
      chain reaction (rRT-PCR). MATERIALS AND METHODS: From July 2007 to July 2009, 100
      respiratory samples (nasal and throat swabs) were collected from paediatric
      patients with acute respiratory symptoms. attending out patients department, and
      admitted to the paediatric wards of B. J. Wadia Hospital for Children, Mumbai.
      The samples were collected and processed as per World Health Organization (WHO)
      guidelines. Viral RNA was extracted and one-step rRT-PCR was performed to detect
      influenza type A (H1 and H3) and influenza type B virus. RESULTS: Out of 100
      samples processed by rRT-PCR, a total of 11 samples (11%) were positive for
      influenza virus. The typing for influenza A subtypes showed 1% (1) positivity for
      H1 and 5% (5) positivity for H3 subtypes and 5% (5) samples tested positive for
      influenza type B virus. CONCLUSION: It was observed that both influenza type A
      and B viruses were prevalent in Mumbai during the study period. Such surveillance
      data are important in the early detection of any antigenic variants that may be
      helpful in global influenza vaccine preparation and for any pandemic preparedness
      activity.

PMID- 22664430
TI  - The non-association of Panton-Valentine leukocidin and mecA genes in the genome
      of Staphylococcus aureus from hospitals in South Western Nigeria.
AB  - PURPOSE: Virulence genes play important roles in pathogenesis of infections
      caused by S. aureus. The aim of this study was to determine the prevalence of
      PVL, eta and mecA genes in S. aureus isolated from patients in South-Western
      Nigeria. MATERIALS AND METHODS: In this study, a total of 116 S. aureus isolates
      from the clinical specimens submitted to laboratories in tertiary hospitals in
      the South Western Nigeria were used. Antibiotic susceptibility test was carried
      out to determine the susceptibility pattern of the isolates using multiple
      antibiotics disc. Minimum inhibitory concentration (MIC) was also carried out to
      determine the degree of resistant of the isolates to methicillin. PCR was used to
      screen for the presence of PVL, eta, and mecAgenes. RESULTS: mecA gene was
      detected in 48 (41.4%) of 116 strains of S. aureus. The MIC 50 and MIC 90 for
      mecA negative strains were 1 and 8 MUg/ml, respectively while the MIC 50 and MIC
      90 for mecA positive were >256 MUg/ml. Twenty eight (24.1%) of 116 isolates were
      PVL gene positive with none of them mecA+. The prevalence of community acquired
      MRSA (CA-MRSA) was estimated to be 6.9% using molecular techniques. No
      localization of mecA gene and PVL gene on the genome of the entire S. aureus
      strains studied. Site of isolation of organism /specimen type was found to be
      associated with the prevalence of PVL+ and mecA+ S. aureus (P< 0.01). CONCLUSION:
      This study concludes that the PVL+ MRSA is rare and the prevalence of CA-MRSA is
      low in South-Western, Nigeria.

PMID- 22664431
TI  - Detection of various types of resistance patterns and their correlation with
      minimal inhibitory concentrations against clindamycin among methicillin-resistant
      Staphylococcus aureus isolates.
AB  - PURPOSE: The macrolide lincosamide streptogramin B (MLS B ) family of antibiotics
      serves as an alternative for the treatment of skin and soft tissue infections
      caused by methicillin-resistant Staphylococcus aureus (MRSA). However, resistance
      to clindamycin too has emerged, which is of two types, inducible and
      constitutive. Therapeutic failure is common with inducible type of clindamycin
      resistance. This study was done to determine the various clindamycin resistance
      patterns in MRSA isolates and to compare them with minimal inhibitory
      concentration (MIC) of clindamycin. MATERIALS AND METHODS: Fifty MRSA isolates
      were studied by disc approximation test (D test) to detect inducible iMLS B
      resistance and MIC by agar dilution technique. RESULTS: Of the 50 isolates, 34
      were sensitive to both clindamycin and erythromycin. 16 isolates showed different
      sensitivity patterns; nine of these were positive for D zone indicating inducible
      iMLS B resistance, five were positive for constitutive MLS B resistance and two
      showed possible efflux mechanism for macrolide resistance. Out of the 34
      sensitive isolates, 5 showed isolated colonies (subpopulation) inside the
      clindamycin-sensitive zone. When these sub-populations were tested further, two
      were constitutive MLS B phenotypes, two were inducible iMLS B and one was HD
      (hazy D zone), which is D + with growth up to clindamycin disc (which is also
      considered as constitutive MLS B phenotype). Seven isolates showed an MIC of >=4
      MUg/ml to clindamycin in spite of being susceptible to both erythromycin and
      clindamycin by Kirby Bauer disc diffusion technique. Out of these seven isolates,
      five were those which grew as subpopulation inside the clindamycin-sensitive
      zone. CONCLUSION: Detection of iMLS B resistance among MRSA helps to avoid
      treatment failure with clindamycin. Studying the subpopulation inside the
      clindamycin-sensitive zone raises the question of existence of hetero-resistance
      or some other mechanism, which needs further study.

PMID- 22664432
TI  - Comparison of disc and MIC reduction methods with polymerase chain reaction for
      the detection of metallo-beta-lactamase in Pseudomonas aeruginosa.
AB  - PURPOSE: The present study was undertaken to evaluate the screening antibiotic,
      confirmatory phenotypic test and agent against PCR as gold standard and to detect
      the prevalent MBL gene. MATERIALS AND METHODS: Three hundred and twenty-six
      Pseudomonas aeruginosa isolates were screened for resistance to Imipenem (IPM),
      Meropemem (MEM) and Ceftazidime (CAZ) by disc diffusion. Isolates resistant to
      any of these were considered screen test-positive for MBL and were subjected to
      Double disc synergy test (DDST) and Disc potentiation test (DPT: Using IPM, MEM
      and CAZ alone and with EDTA), Minimum inhibitory concentration (MIC) reduction
      [four-fold or more reduction in MIC of IPM and MEM in presence of chelators: EDTA
      and 1,10-phenanthroline (EPI/EPM: EDTA-phenanthroline- Imipenem/Meropenem Broth
      Microdilution method)] and polymerase chain reaction (PCR) for blaIMP and blaVIM
      . RESULTS: Screen test-positives by MEM and CAZ were 19.3% as against 17.8% by
      IPM. MEMDDST, DPT and EPM confirmed 100% screen-test positives as against 93.7%
      by CAZ DDST and DPT-2, 76.2% by CAZ DPT-1, 88.9% by IPM DDST, 85.7% by IPM DPT-1
      and 92.1% by EPI. IPMand CAZ DDST together confirmed 100% while IPM and CAZ DPT-2
      confirmed 96.8%. All 63 screen-test positives showed the presence of blaVIM .
      CONCLUSIONS: MEM was found to be the best screening and confirmatory agent for
      MBL detection and blaVIM was found to be the prevalent MBL gene in this part of
      the country.

PMID- 22664433
TI  - Molecular screening of virulence genes in high-level gentamicin-resistant
      Enterococcus faecalis and Enterococcus faecium isolated from clinical specimens
      in Northwest Iran.
AB  - PURPOSE: The present study screened clinical isolates of Enterococcus faecalis
      and Enterococcus faecium to determine the prevalence of high-level gentamicin
      resistant enterococci and the potential virulence genes among them. MATERIALS AND
      METHODS: Clinical enterococcal isolates were obtained from three university
      teaching hospitals in Northwest Iran. Isolated enterococci were identified
      phenotypically followed by antibiotic susceptibility testing. Multiplex PCR was
      performed for the detection of genus, species-specific targets, gentamicin
      resistance, and potential virulence genes. RESULTS: Of 220 enterococcal isolates,
      133 (60.45%) isolates were identified as high-level gentamicin-resistant. Of
      these isolates, 79 (59.4%) and 54 (40.6%) were E. faecalis and E. faecium,
      respectively. All high-level gentamicin-resistant strains carried aac(6')Ie
      aph(2")Ia. Of 220 isolates, 65.9% were positive for gelE, and 55%, 53.6%, 51.8%,
      and 49.5% of isolates were positive for cpd, asa1, ace, and esp, respectively.
      Phenotypically detected beta-haemolytic strains (19.54%) were found to possess
      cylL ls MAB. CONCLUSION: The study revealed that high-level gentamicin-resistance
      was related to the presence of aac(6')Ie-aph(2")Ia. Isolated enterococci
      harboured potential virulence determinants, which were more common among E.
      faecalis than among E. faecium strains.

PMID- 22664434
TI  - Detection of 123 bp fragment of insertion element IS6110 Mycobacterium
      tuberculosis for diagnosis of extrapulmonary tuberculosis.
AB  - PURPOSE: Extrapulmonary tuberculosis (EPTB) is emerging problem in developing and
      developed countries. The diagnosis of EPTB in its different clinical
      presentations remains a true challenge. IS6110-based polymerase chain reaction
      (PCR) is used for rapid identification and positivity rate of the Mycobacterium
      tuberculosis complex in clinical isolates of different sites of EPTB. The present
      study was carried out to study the prevalence of M. tuberculosis complex in
      clinical isolates of EPTB at tertiary care centres in Lucknow. MATERIALS AND
      METHODS: Seven hundred fifty-six specimens were collected from the suspected
      cases of EPTB which were processed for Mycobacteria by Ziehl Neelson (ZN)
      staining and BACTEC culture. All the specimens were also processed for IS6110
      based PCR amplification with primers targeting 123 bp fragment of insertion
      element IS6110 of the M. tuberculosis complex. RESULTS: Of these 756 specimens,
      71(9.3%) were positive for acid fast bacilli (AFB) by ZN staining, 227(30.1%)
      were positive for mycobacteria by BACTEC culture and IS6110 PCR were positive for
      M. tuberculosis complex in 165 (20.7%) isolates. We found a significant
      difference in sensitivities of different tests (P<0.05). CONCLUSIONS: This study
      reveals the positivity of M. tuberculosis complex in clinical isolates of EPTB
      case in tertiary care hospitals in Northern India. 72.7% of M. tuberculosis
      complex was confirmed by IS6110-PCR in culture isolates from different sites of
      EPTB. The high prevalence of the M. tuberculosis complex was seen in lymph node
      aspirate and synovial fluid. However, utility of PCR may play a potentially
      significant role in strengthening the diagnosis of EPTB especially targeting
      IS6110.

PMID- 22664435
TI  - Comparative evaluation of paired blood culture (aerobic/aerobic) and single blood
      culture, along with clinical importance in catheter versus peripheral line at a
      tertiary care hospital.
AB  - PURPOSE: Paired blood culture (PBC) is uncommon practice in hospitals in India,
      leading to delayed and inadequate diagnosis. Also contamination remains a
      critical determinant in hampering the definitive diagnosis. OBJECTIVES: To
      establish the need of PBC over single blood culture (SBC) along with the degree
      of contamination, this comparative retrospective study was initiated. MATERIALS
      AND METHODS: We processed 2553 PBC and 4350 SBC in BacT/ALERT 3D (bioMerieux)
      between October 2010 and June 2011. The positive cultures were identified in
      VITEK 2 Compact (bioMerieux). True positivity and contaminants were also analyzed
      in 486 samples received from catheter and peripheral line. RESULTS: Out of 2553
      PBC samples, positivity was seen in 350 (13.70%). In 4350 SBC samples, positivity
      was seen in 200 samples (4.59%). In PBC true pathogens were 267 (10.45%) and
      contaminants were 83 (3.25%), whereas in SBC 153 (3.51%) were true positives and
      contaminants were 47 (1.08%). Most of the blood cultures (99.27 %) grew within 72
      h and 95.8% were isolated within 48 h. In 486 PBCs received from
      catheter/periphery (one each), catheter positivity was found in 85 (true
      positives were 48, false positives 37). In peripheral samples true positives were
      50 and false positives were 8. CONCLUSION: Significantly higher positive rates
      were seen in PBCs compared with SBCs. Automated blood culture and identification
      methods significantly reduced the time required for processing of samples and
      also facilitated yield of diverse/rare organisms. Blood culture from catheter
      line had higher false positives than peripheral blood culture. Thus every
      positive result from a catheter must be correlated with clinical findings and
      requires further confirmation.

PMID- 22664436
TI  - Construction of a recombinant plasmid harbouring the glyceraldenyde-3-phosphate
      dehydrogenase gene of periodic Brugia malayi and observation on DNA immunity.
AB  - PURPOSE: Controlling and eliminating lymphatic filariasis will require further
      research of preventative measures and implementation. Parasite is dependent on
      glycolysis for ATP production. The glycolytic enzyme glyceraldenyde-3-phosphate
      dehydrogenase (GAPDH) plays an important role in glycolysis and therefore is
      either a potential target for anti-parasite drug development or a vaccine
      candidate. Therefore, we tried to investigate the DNA vaccine-elicited immune
      responses in BALB/c mice. MATERIALS AND METHODS: We cloned a gene encoding the
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from periodic Brugia malayi into
      vector pcDNA3.1. Mice were injected at a dosage of 100 MUg recombinant plasmid
      DNA with CpG intramuscular injection and immunized three times at 2-week
      intervals. pcDNA3.1 and normal saline were used as control. The tissue of muscles
      at the 4 weeks after the third injection was collected and target genes were
      detected using RT-PCR. The humoral responses elicited in mice by inoculation with
      the recombinant plasmid pcDNA3.1-BmGAPDH were detected using a standard ELISA.
      Two weeks after the third immunization, stimulation index (SI) was measured using
      the MTT method and the level of secreted IL-4 and INF-g were detected using
      ELISA. RESULTS: Specific gene fragment coding GAPDH was amplified and the
      recombinant plasmid pcDNA3.1-BmGAPDH was constructed. Post-challenge sera from
      the mice immunized with the DNA vaccine had specific antibody titres of 1:1600 to
      1:6400, and the highest titre was observed in the mice that were inoculated by
      pcDNA3.1-BmGAPDH/CpG at 6 weeks. At 4 weeks after immunization, the spleens of
      the mice were obviously enlarged. The proliferation of spleen T lymphocytes seen
      on the MTT assay was higher in the pcDNA3.1-BmGAPDH group than in the control
      group (P value <0.05). The levels of IL-4 and INF-gamma in serums from the
      immunized mice were significantly higher than that of the control (P value
      <0.05). CONCLUSIONS: We conclude that the recombinant eukaryotic plasmid pcDNA3.1
      BmGAPDH could elicit humoral and cellular immune responses in mice.

PMID- 22664437
TI  - Does antimicrobial use increase the rate of antimicrobial resistance? A one year
      experience.
AB  - Antimicrobial resistance has been a challenge in all countries. The aim of this
      study is to ascertain the risk factors that predispose patients to infections
      with extended spectrum beta lactamase (ESBL)-producing gram-negative bacteria and
      methicillin-resistant Staphylococcus aureus (MRSA). Patients who were treated in
      the secondary care hospital due to infections in 2009 and their isolates were
      evaluated retrospectively. In total, 174 patients and their 189 isolates, which
      contained 36 ESBL-producing gram-negative bacteria, 112 non-ESBL-producing gram
      negative bacteria, and 41 gram-positive bacteria were evaluated retrospectively.
      Hospitalisation in the previous 3 months, comorbidity, and usage of amoxicillin
      clavulanate in the previous 3 months were determined to be the risk factors
      associated with infections by the ESBL-producing gram-negative bacteria.
      Hospitalisation was found to be a risk factor for infection with MRSA.
      Hospitalisation and underlying conditions increase the colonisation with
      resistant bacteria and resistance rates in the patients, hospitals and
      communities. An infection control programme should be contemplated not only for
      hospitals, but also for the greater community.

PMID- 22664439
TI  - Multidrug-resistant tuberculosis in children from 2003 to 2005: a brief report.
AB  - Multidrug-resistant tuberculosis (MDR-TB) has rarely been reported from children
      in India. Their response to therapy is also not known. We present four HIV
      negative children with MDR-TB (3 children with extra-pulmonary TB and 1 child
      with pulmonary TB) who presented in 2003-2005. All the four children were already
      on antituberculous therapy (ATT) for 3-9 months prior to being detected as MDR
      TB. These patients were started on second-line ATT for 18 months. In three
      patients, there was complete resolution, and one patient with severe bilateral
      pulmonary TB had the disease localized to one lung after 18 months of therapy.

PMID- 22664438
TI  - ermA, ermC , tetM and tetK are essential for erythromycin and tetracycline
      resistance among methicillin-resistant Staphylococcus aureus strains isolated
      from a tertiary hospital in Malaysia.
AB  - The objective of this study was to determine the expression and transferability
      of tetracycline and erythromycin resistance among 188 MRSA strains from a
      Malaysian tertiary hospital. The minimum inhibitory concentrations (MICs) for
      oxacillin, erythromycin, tetracycline and ciprofloxacin ranged from 4 to 512
      MUg/ml, 0.25 to 256 MUg/ml, 0.5 to 256 MUg/ml and 0.5 to 512 MUg/ml,
      respectively. Tetracycline-resistant strains showed co-resistance towards
      ciprofloxacin and erythromycin. There was a significant increase (P<0.05) of high
      level tetracycline (>=MIC 256 MUg/ml) and erythromycin (>=MIC 128 MUg/ml)
      resistant strains in between the years 2003 and 2008. All erythromycin-resistant
      strains harboured ermA or ermC gene and all tetracycline-resistant strains
      harboured tetM or tetK gene. The blaZ was detected in all MRSA strains, whereas
      ermA, tetM, ermC, tetK and msrA genes were detected in 157 (84%), 92 (49%), 40
      (21%), 39 (21%) and 4 (2%) MRSA strains, respectively. The blaZ, tetM, ermC and
      tetK genes were plasmid-encoded, with ermC gene being easily transmissible.
      Tn5801-like transposon was present in 78 tetM-positive strains. ermA and tetM
      genes were the most prevalent erythromycin and tetracycline resistance
      determinants, respectively, in MRSA strains. The association of resistance genes
      with mobile genetic elements possibly enhances the spread of resistant traits in
      MRSA.

PMID- 22664440
TI  - Detection of bacterial growth in blood components using oxygen consumption as a
      surrogate marker in a tertiary oncology setup.
AB  - Microbiological contamination of blood and blood products is a well-recognised
      transfusion risk. This study was performed in the blood bank of our oncology
      centre, with an objective to detect bacterial contamination in our blood products
      using oxygen consumption as a surrogate marker [Pall Enhanced Bacterial Detection
      System (eBDS)]. Results revealed that the percentages of failed units were 1.16%
      for random donor platelets (RDP), 0.81% for single donor platelets (SDP) and
      2.94% for packed red blood cells (PRBCs), of which one RDP and one SDP grew
      coagulase-negative staphylococcus, while one PRBC culture grew Gram-positive
      bacilli.

PMID- 22664441
TI  - Be alert to the alterations in the biological characteristics in heterogeneous
      vancomycin-intermediate Staphylococcus aureus.
AB  - The development of reduced vancomycin susceptibility in Staphylococcus aureus in
      many cases appears to be associated with characteristic changes. These changes
      may have pitfall of identifying S. aureus by automated testing methods like Vitek
      32. In this study, we retested 24 heterogeneous vancomycin-intermediate
      Staphylococcus haemolyticus (h-VISH) collected in 2008-2010 at the Department of
      Clinical Microbiology by conventional biochemical tests and polymerase chain
      reaction (PCR). The heterogeneous vancomycin-intermediate S. aureus (hVISA)
      reversion test and electron microscopic examination were also used. Six isolates
      of 24 h-VISH possessed nuc, coa, and 16S rRNA genes, and could be reversed into
      S. aureus. It suggested that biochemical and morphological changes in hVISA and
      vancomycin-intermediate S. aureus (VISA) should be considered, and the detection
      of S. aureus, especially reduced vancomycin susceptibility isolates, requires
      more attention and different techniques.

PMID- 22664442
TI  - Presumptive identification of Mycobacterium tuberculosis complex based on cord
      formation in BACTEC MGIT 960 medium.
AB  - We considered samples received for culture of mycobacteria using BACTEC MGIT 960
      system over a period of 1 year. Tubes flagged positive by MGIT were evaluated for
      presence of serpentine cording. The cord formation was compared with isolates
      identified as Mycobacterium tuberculosis complex (MTC) based on p-nitrobenzoic
      acid (PNB) test. Cords were found in 591 isolates of which 584 (98.8%) were
      confirmed as MTC. The sensitivity and specificity of cord formation were found to
      be 99.7% and 89.9%, respectively.

PMID- 22664443
TI  - Awareness of changing trends in epidemiology of dengue fever is essential for
      epidemiological surveillance.
AB  - Dengue has become endemic in India with outbreaks occurring almost every year.
      The seroprevalence and serotypic data of the last 7 years in samples obtained
      from suspected dengue patients from a tertiary care hospital were analyzed. Out
      of 7846 serum samples received in the virology laboratory from suspected dengue
      cases during 2002 to 2008, 2366 (30.15%) were serologically confirmed. Serotyping
      was done using mRT-PCR. All the four serotypes were detected in 2003, while data
      in 2004, 2005 and 2006 revealed the the predominance of Den-3. In the year 2007
      predominance of Den-2 was observed, whereas in 2008 Den-1 was the most common
      serotype isolated. Overall, Den-2 and Den-3 were the most predominant serotypes
      during 2003-2007 but Den-1 replaced these strains in the year 2008. Since the
      emergence of a new predominant strain can lead to the occurrence of an outbreak,
      presence of Den-1 in the year 2008 would pose an alarming situation before us.
      Well-targeted population-based epidemiological studies are urgently required to
      control dengue menace.

PMID- 22664444
TI  - Relapse of kala-azar after use of multiple drugs: a case report and brief review
      of literature.
AB  - We present a case of kala-azar infection that recurred in a patient after
      completion of the standard treatment course of miltefosine, amphotericin B
      deoxycholate (short course), and amphotericin B lipid formulations. The patient
      was cured after continuous amphotericin B-deoxycholate administration for 4
      weeks. This is a unique case of relapse following the use of three important
      drugs. Although amphotericin B-deoxycholate is a second line drug in Nepal, it
      has shown a satisfactory clinical response with continuous treatment for 4 weeks.
      Therefore, an extended course of amphotericin B-deoxycholate may be beneficial in
      patients with resistance to the standard short course and other anti-leishmania
      drugs.

PMID- 22664445
TI  - Trichosporon inkin, an unusual agent of fungal sinusitis: a report from south
      India.
AB  - The aetiology of fungal sinusitis is diverse and changing. Aspergillus species
      has been the most common cause for fungal sinusitis, especially in dry and hot
      regions like India. Trichosporon species as a cause for fungal sinusitis has been
      very rarely reported the world over. Here, we report a rare case of allergic
      fungal sinusitis caused by Trichosporon inkin in a 28-year-old immunocompetent
      woman. Bilateral nasal obstruction, nasal discharge and loss of smell were her
      presenting complaints. Diagnostic nasal endoscopy showed bilateral multiple
      polyps. Functional endoscopic sinus surgery was performed and many polyps were
      removed. Based on mycological and histopathological studies, the pathogen was
      identified as T. inkin.

PMID- 22664446
TI  - The first case of Staphylococcus aureus ST398 causing bacteremia in an
      immunocompromised patient in Greece.
AB  - We describe a case of catheter-related bloodstream infection, in a patient with
      colon cancer, caused by a methicillin-sensitive Staphylococcus aureus strain,
      nontypeable by pulsed field gel electrophoresis of SmaI macrorestriction fragment
      analysis, belonging to ST398. The patient recovered after daptomycin therapy.
      This is the first report that documents the emergence of ST398 in Greece.

PMID- 22664447
TI  - Human intestinal capillariasis: a rare case report from non-endemic area (Andhra
      Pradesh, India).
AB  - Human intestinal capillariasis is caused by Capillaria philippinensis. This
      disease is endemic in Philippines and Thailand. To the best of our knowledge, we
      report the third case of human intestinal capillariasis from India and the first
      case from Andhra Pradesh, which is a non-endemic area. A 40-year-old female
      presented with diarrhoea, vomiting, decreased urinary output, ascitis, pedal
      oedema, hypoalbuminemia, and electrolyte imbalance. Microscopic examination of
      stool sample revealed the presence of ova, larvae, and adult worms of C.
      philippinensis. Patient recovered from the disease after taking albendazole 400
      mg daily for 1 month along with supportive treatment.

PMID- 22664448
TI  - Use of John Cunningham virus polymerase chain reaction in the diagnosis of
      progressive multifocal leucoencephalopathy - a rare presenting manifestation in
      an HIV-positive patient.
AB  - John Cunningham virus infection is an important cause of progressive multifocal
      leucoencephalopathy (PML) in the context of advanced human immunodeficiency virus
      infection. Limited data are available regarding the true incidence of PML as a
      presenting manifestation of HIV. We report one such case and also highlight the
      effective use of polymerase chain reaction in confirming its diagnosis.

PMID- 22664449
TI  - Fatal meningitis caused by vancomycin-resistant enterococci: report of two cases
      from south India.
AB  - Vancomycin-resistant enterococci rarely cause meningitis and present a
      therapeutic challenge. Antimicrobial susceptibility testing was done for strains
      of Enterococcus species isolated from CSF samples of patients with meningitis by
      phenotypic methods. Multiplex polymerase chain reaction was performed to
      determine the genetic basis of vancomycin resistance of such isolates. We report
      here two cases of enterococcal meningitis caused by vancomycin-resistant
      Enterococcus species. One of the isolates was identified as Enterococcus faecalis
      and the other as Enterococcus gallinarum. We also report the simultaneous
      presence of vanC1 and vanA resistance genes in the strain of E. gallinarum. To
      the best of our knowledge, this is the first report of vanA resistance gene in an
      isolate of E. gallinarum from the Indian subcontinent. This is also the first
      Indian report of vancomycin-resistant Enterococcus causing meningitis.

PMID- 22664450
TI  - Vertebro-cerebral cryptococcosis mimicking tuberculosis: a diagnostic dilemma in
      countries with high burden of tuberculosis.
AB  - We report a case of a 30-year-old immunocompetent man with disseminated
      cryptococcosis who was initially treated with antitubercular therapy due to
      clinical and radiological diagnosis of vertebro-cerebral tuberculosis. The
      diagnosis of Cryptococcus infection was made due to incidental isolation of this
      fungus from blood culture with negative cerebrospinal fluid culture results.
      Though disseminated cryptococcosis with central nervous system, skeletal, and
      skin involvement is an uncommon manifestation of Cryptococcus neoformans
      infection, a high clinical suspicion and early initiation of therapy is needed to
      recognise and treat such patients efficiently.

PMID- 22664451
TI  - Comment on: Schizophyllum commune sinusitis in an immunocompetent host.

PMID- 22664452
TI  - Ethical issues on carrying out research on archived samples.

PMID- 22664453
TI  - Diagnosis of congenital toxoplasmosis by polymerase chain reaction.

PMID- 22664455
TI  - Article published elsewhere as abstract.

PMID- 22664454
TI  - Comparative evaluation of Latex agglutination method with other phenotypic
      methods for detection of methicillin-resistant Staphylococcus aureus.

PMID- 22664456
TI  - Iodine-129 in animal thyroids from Argentina.
AB  - (129)I and (127)I concentrations in animal thyroids coming from several regions
      of Argentina were determined by accelerator mass spectrometry (AMS) and gas
      chromatography (GC), respectively. The measured (129)I/(127)I ratios, ranging
      from 3 * 10(-12) to 4 * 10(-10), are significantly lower than those typical for
      areas in the northern hemisphere (10(-10)-10(-7)). The (129)I concentrations show
      a clear dependence with latitude and season, which can be understood considering
      tropospheric circulation patterns, possible (129)I sources and regional
      precipitation rates.

PMID- 22664458
TI  - Calcium phosphate-mediated gene delivery using simulated body fluid (SBF).
AB  - The present study aimed at developing a new approach in gene delivery of calcium
      phosphate nanoparticles through simulated body fluid (CaP-SBF). The
      physicochemical and biological characteristics of the CaP-SBF nanoparticles were
      compared with those made in pure water (CaP-water) via a similar procedure. The
      CaP-SBF and CaP-water solutions were then adjusted to two different pH values of
      7.4 and 8.0, mixed with plasmid DNA (pDNA), and added in varying amounts to human
      embryonic kidney (HEK 293T) cells. The transfection efficiency and cell viability
      were studied in vitro by reporter gene (luciferase and Enhanced Green Fluorescent
      Protein) expression and the resazurin reduction assay, respectively, 24 and 48 h
      after the incubation with the nanoparticles. Our results indicated considerably
      high in vitro transfection efficiency for CaP-SBF/DNA complexes at physiological
      pH (7.4) with high amounts of CaP. Additionally, the SBF solution exhibited the
      ability to reduce the rapid growth of CaP particles over time, leading to higher
      transfection efficiency of CaP-SBF/DNA complexes than those made in water (CaP
      water/DNA).

PMID- 22664457
TI  - 1(st) French-Israeli International Conference on B Cells and therapeutic
      antibodies: October 23-25, 2011 Jerusalem, Israel.

PMID- 22664459
TI  - Multifunctional poly (lactide-co-glycolide) nanoparticles for
      luminescence/magnetic resonance imaging and photodynamic therapy.
AB  - Poly (lactide-co-glycolide) (PLGA) coupled with methoxy poly (ethylene glycol)
      (mPEG) or chlorin e6 (Ce6) was synthesized using the Steglich esterification
      method. PLGA-linked mPEG (PLGA-mPEG), PLGA-linked Ce6 (PLGA-Ce6), and Fe(3)O(4)
      were utilized to constitute multifunctional PLGA nanoparticles (~160 nm) via the
      multi-emulsion W(1)/O/W(2) (water-in-oil-in-water) method. The photo-sensitizing
      properties of Ce6 molecules anchored to PLGA nanoparticles enabled in vivo
      luminescence imaging and photodynamic therapy for the tumor site. The
      encapsulation of Fe(3)O(4) allowed high contrast magnetic resonance (MR) imaging
      of the tumor in vivo. Overall, PLGA nanoparticles resulted in a significant tumor
      volume regression for the light-illuminated KB tumor in vivo and enhanced the
      contrast at the tumor region, compared to that of Feridex((r)) (commercial
      contrast agent).

PMID- 22664460
TI  - Synthesis, characterization of chitosan-tripolyphosphate conjugated chloroquine
      nanoparticle and its in vivo anti-malarial efficacy against rodent parasite: a
      dose and duration dependent approach.
AB  - Various strategies to deliver antimalarials using nanocarriers have been
      evaluated. However, taking into account the peculiarities of malaria parasites,
      the focus is placed mainly polymer-based chitosan nanocarriers. Our purpose of
      the study is to develop chitosan-tripolyphosphate (CS-TPP) nanoparticles (NPs)
      conjugated chloroquine in application for attenuation of Plasmodium berghei
      infection in Swiss mice. NPs were prepared by ionotropic gelation between CS and
      sodium TPP. In the study, the interaction of CS and TPP and the presence of
      chloroquine at the surface of chitosan-TPP NPs have been investigated by means of
      different methods like FTIR, DLS, and zeta potential. After drug preparation,
      effective dose of the nanoconjugated chloroquine (Nch) among 100, 250, and 500
      mg/kg bw/day, was studied against P. berghei infection in Swiss mice by blood
      smear staining and biochemical assay of different inflammatory markers, and
      antioxidant enzyme levels also performed. After evaluating the effective dose,
      dose-dependent duration study was performed for 5, 10, 15 days. From the present
      study the maximum effect of Nch was found at 250 mg/kg bw concentration for 15
      days treatment. So, this Nch might have potential of application as therapeutic
      anti-malarial and antioxidant agent.

PMID- 22664461
TI  - Fully biodegradable and cationic poly(amino oxalate) particles for the treatment
      of acetaminophen-induced acute liver failure.
AB  - Acute inflammatory diseases are one of major causes of death in the world and
      there is great need for developing drug delivery systems that can target drugs to
      macrophages and enhance their therapeutic efficacy. Poly(amino oxalate) (PAOX) is
      a new family of fully biodegradable polymer that possesses tertiary amine groups
      in its backbone and has rapid hydrolytic degradation. In this study, we developed
      PAOX particles as drug delivery systems for treating acute liver failure (ALF) by
      taking the advantages of the natural propensity of particulate drug delivery
      systems to localize to the mononuclear phagocyte system, particularly to liver
      macrophages. PAOX particles showed a fast drug release kinetics and excellent
      biocompatibility in vitro and in vivo. A majority of PAOX particles were
      accumulated in liver, providing a rational strategy for effective treatment of
      ALF. A mouse model of acetaminophen (APAP)-induced ALF was used to evaluate the
      potential of PAOX particles using pentoxifylline (PTX) as a model drug. Treatment
      of PTX-loaded PAOX particles significantly reduced the activity of alanine
      transaminase (ALT) and inhibited hepatic cell damages in APAP-intoxicated mice.
      The high therapeutic efficacy of PTX-loaded PAOX particles for ALF treatment may
      be attributed to the unique properties of PAOX particles, which can target
      passively liver, stimulate cellular uptake and trigger a colloid osmotic
      disruption of the phagosome to release encapsulated PTX into the cytosol. Taken
      together, we believe that PAOX particles are a promising drug delivery candidate
      for the treatment of acute inflammatory diseases.

PMID- 22664462
TI  - Hyperbranched PEGmethacrylate linear pDMAEMA block copolymer as an efficient non
      viral gene delivery vector.
AB  - A unique hyperbranched polymeric system with a linear poly-2-dimethylaminoethyl
      methacrylate (pDMAEMA) block and a hyperbranched polyethylene glycol methyl ether
      methacrylate (PEGMEMA) and ethylene dimethacrylate (EGDMA) block was designed and
      synthesized via deactivation enhanced atom transfer radical polymerisation (DE
      ATRP) for efficient gene delivery. Using this unique structure, with a linear
      pDMAEMA block, which efficiently binds to plasmid DNA (pDNA) and hyperbranched
      polyethylene glycol (PEG) based block as a protective shell, we were able to
      maintain high transfection levels without sacrificing cellular viability even at
      high doses. The transfection capability and cytotoxicity of the polymers over a
      range of pDNA concentration were analysed and the results were compared to
      commercially available transfection vectors such as polyethylene imine (branched
      PEI, 25 kDa), partially degraded poly(amido amine)dendrimer (dPAMAM; commercial
      name: SuperFect((r))) in fibroblasts and adipose tissue derived stem cells
      (ADSCs).

PMID- 22664463
TI  - 1H-nuclear magnetic resonance analysis of the triacylglyceride composition of
      cold-pressed oil from Camellia japonica.
AB  - Camellia japonica (CJ) has oil-rich seeds, but the study of these oils has
      received little attention and has mainly focused only on their health properties.
      In the present work the relative composition of the fatty acid (FA) components of
      the triglycerides in cold-pressed oil from CJ is studied by 1H-NMR. The results
      obtained were: 75.75%, 6.0%, 0.17% and 18.67%, for oleic, linoleic, linolenic and
      saturated FA respectively. Levels of C18 unsaturated FA found in CJ oil were
      similar to those reported for olive oils. We also checked the possibility of
      using 13C-NMR spectroscopy; however, the results confirmed the drawback of 13C
      over 1H-NMR for the study of FA components of CJ triglycerides due to its low
      gyromagnetic ratio and its very low natural abundance.

PMID- 22664464
TI  - The role of bioactive compounds on the promotion of neurite outgrowth.
AB  - Neurite loss is one of the cardinal features of neuronal injury. Apart from
      neuroprotection, reorganization of the lost neuronal network in the injured brain
      is necessary for the restoration of normal physiological functions. Neuritogenic
      activity of endogenous molecules in the brain such as nerve growth factor is well
      documented and supported by scientific studies which show innumerable compounds
      having neurite outgrowth activity from natural sources. Since the damaged brain
      lacks the reconstructive capacity, more efforts in research are focused on the
      identification of compounds that promote the reformation of neuronal networks. An
      abundancy of natural resources along with the corresponding activity profiles
      have shown promising results in the field of neuroscience. Recently, importance
      has also been placed on understanding neurite formation by natural products in
      relation to neuronal injury. Arrays of natural herbal products having plentiful
      active constituents have been found to enhance neurite outgrowth. They act
      synergistically with neurotrophic factors to promote neuritogenesis in the
      diseased brain. Therefore use of natural products for neuroregeneration provides
      new insights in drug development for treating neuronal injury. In this study,
      various compounds from natural sources with potential neurite outgrowth activity
      are reviewed in experimental models.

PMID- 22664465
TI  - Short and long-term effects of Baccharis articulata on glucose homeostasis.
AB  - In this study, the in vivo effect of the crude extract and n-butanol and aqueous
      residual fractions of Baccharis articulata (Lam.) Pers. on serum glucose levels,
      insulin secretion and liver and muscle glycogen content, as well as in vitro
      action on serum intestinal disaccharidase activity and albumin glycation were
      investigated. Oral administration of the extract and fractions reduced glycemia
      in hyperglycemic rats. Additionally, the n-butanol fraction, which has high
      flavonoids content, stimulated insulin secretion, exhibiting an insulinogenic
      index similar to that of glipizide. Also, the n-butanol fraction treatment
      significantly increased glycogen content in both liver and muscle tissue. In
      vitro incubation with the crude extract and n-butanol and aqueous residual
      fractions inhibited maltase activity and the formation of advanced glycation end
      products (AGEs). Thus, the results demonstrated that B. articulata exhibits a
      significant antihyperglycemic and insulin-secretagogue role. These effects on the
      regulation of glucose homeostasis observed for B. articulata indicate potential
      anti-diabetic properties.

PMID- 22664466
TI  - Response surface optimized ultrasonic-assisted extraction of flavonoids from
      Sparganii rhizoma and evaluation of their in vitro antioxidant activities.
AB  - An efficient ultrasound-assisted extraction technique was employed to extract
      total flavonoids from Sparganii rhizoma. The optimum extraction conditions for
      the highest yield of total flavonoids were ethanol concentration 53.62%,
      ultrasonication time 29.41 min and ultrasound power 300 W, which were determined
      using response surface methodology. The extraction yields of the optimal
      ultrasound-assisted extraction were higher than using conventional extraction.
      The crude extract was then purified on a polyamide resin, whereby the flavonoids
      content in the purified extract increased to 94.62%. The antioxidant activities
      of the purified flavonoids including DPPH radical scavenging activity, ABTS+
      radical scavenging activity, reducing power, hydroxyl radical scavenging activity
      and superoxide anion scavenging activity, were evaluated in vitro, which
      suggested that the flavonoids showed significant antioxidant activities. Rutin,
      kaempferol and formononetin were identified in the extract by comparing relative
      retention times and UV-Vis spectra with those of reference standards.

PMID- 22664467
TI  - Improved methods for thermal rearrangement of alicyclic alpha-hydroxyimines to
      alpha-aminoketones: synthesis of ketamine analogues as antisepsis candidates.
AB  - Ketamine is an analgesic/anesthetic drug, which, in combination with other drugs,
      has been used as anesthetic for over 40 years. Ketamine induces its analgesic
      activities by blocking the N-methyl-D-aspartate (NMDA) receptor in the central
      nervous system (CNS). We have reported that low doses of ketamine administrated
      to patients before incision significantly reduced post-operative inflammation as
      reflected by reduced interleukin-6 (IL-6) sera-levels. Our data demonstrated in a
      rat model of Gram-negative bacterial-sepsis that if we inject a low dose of
      ketamine following bacterial inoculation we reduce mortality from approximately
      75% to 25%. Similar to what we have observed in operated patients, the levels of
      TNF-alpha and IL-6 in ketamine-treated rats were significantly lower than in
      septic animals not treated with ketamine. On the base of these results, we have
      designed and synthesized series of new analogues of ketamine applying a thermal
      rearrangement of alicyclic alpha-hydroxyimines to a-aminoketones in parallel
      arrays. One of the analogues (compound 6e) displayed high activity in down
      regulating the levels of IL-6 and TNF-alpha in vivo as compared to ketamine.

PMID- 22664468
TI  - Synthesis, radiolabeling and biological evaluation of propylene amine oxime
      complexes containing nitrotriazoles as hypoxia markers.
AB  - Two propylene amine oxime (PnAO) complexes, 1, containing a 3-nitro-1,2,4
      triazole and 2, containing two 3-nitro-1,2,4-triazoles, were synthesized and
      radiolabeled with (99m)Tc in high labeling yields. Cellular uptakes of (99m)Tc-1
      and (99m)Tc-2 were tested using a S180 cells line. Under anoxic conditions, the
      cellular uptakes of (99m)Tc-1 and (99m)Tc-2 were 33.7 +/- 0.2% and 35.0 +/- 0.7%
      at 4 h, whereas the normoxic uptakes of the two complexes were 6.0 +/- 1.6% and
      4.6 +/- 0.9%, respectively. Both (99m)Tc-1 and (99m)Tc-2 displayed significant
      anoxic/normoxic differentials. The cellular uptakes were highly dependent on
      oxygen and temperature. Biodistribution studies revealed that both (99m)Tc-1 and
      (99m)Tc-2 showed a selective localization in tumor and slow clearance from it. At
      4 h, the tumor-to-muscle ratios (T/M) were 3.79 for (99m)Tc-1 and 4.58 for
      (99m)Tc-2. These results suggested that (99m)Tc-labeled PnAO complexes (99m)Tc-1
      and (99m)Tc-2 might serve as novel hypoxia markers. By introducing a second
      nitrotriazole redox center, the hypoxic accumulation of the marker was slightly
      enhanced.

PMID- 22664469
TI  - Binding of bezafibrate to human serum albumin: insight into the non-covalent
      interaction of an emerging contaminant with biomacromolecules.
AB  - In recent years, bezafibrate (BZF) has been frequently detected in environmental
      media. In order to reveal the toxicity of such an emerging pollutant, its
      interaction with human serum albumin (HSA) was studied by fluorescence
      spectrometry, circular dichroism, and equilibrium dialysis. Fluorescence data
      showed that the fluorescence quenching of HSA by BZF resulted from the formation
      of HSA-BZF complex. The binding constants were determined to be 3.33 * 103, 2.84
      * 103 M-1 at 298 and 309.5 K, respectively. The thermodynamic determination
      indicated that the hydrophobic and electrostatic interaction were the dominant
      binding force. The conformational investigation showed that the presence of BZF
      increased the alpha-helix content of HSA and induced the slight unfolding of the
      polypeptides of protein. Finally, the equilibrium dialysis showed that 0.56 mM
      BZF decreased the binding of vitamin B2 to HSA by 29%.

PMID- 22664470
TI  - Genes of the interleukin-18 pathway are associated with susceptibility to
      Barrett's esophagus and esophageal adenocarcinoma.
AB  - OBJECTIVES: To investigate the association of genetic polymorphisms of the
      interleukin-18 (IL-18) pathway to Barrett's esophagus (BE) and esophageal
      adenocarcinoma (EAC). Most cases of EAC arise in a background of reflux-induced
      BE. Genetic influences in this pathway are poorly understood. IL-18 is a
      multifunctional cytokine implicated in anti-tumor immunity. A number of
      polymorphisms of the IL-18 and IL-18 receptor-accessory protein (IL-18RAP) genes
      have been reported to alter gene expression and have recently been linked to
      inflammatory processes and various tumors, but have not heretofore been studied
      in BE and EAC. METHODS: Two IL-18 promoter polymorphisms -137 G/C and -607 C/A,
      (rs187238 and rs1946518) and one IL-18RAP polymorphism (rs917997, C/T) were
      analyzed. Each single-nucleotide polymorphism (SNP) was genotyped in the
      following groups: EAC, BE, reflux esophagitis (RE), and controls and analyzed for
      association with disease status. RESULTS: The IL-18RAP rs917997C allele is
      strongly associated with a protective effect in BE (P = 0.0002) and EAC (P = 6 *
      10(-7)), which approaches genome-wide levels of significance for allele
      association without incurring significant multiple testing. The CC genotype at IL
      18RAP locus rs917997 was associated with a protective effect against esophageal
      disease (P = 6 * 10(-4), odds ratio (OR) = 0.59, and 95% confidence interval (CI)
      0.43-0.80 for BE; and P = 2 * 10(-6), OR = 0.46, and 95% CI 0.34-0.64 for EAC).
      The genotype frequencies of IL-18-607 C/A were weakly associated with BE (P =
      0.02), and this trend was also seen between controls and EAC (P = 0.07). The CC
      genotype was associated with an increased risk of BE (OR = 1.45, 95% CI 1.07
      1.98) and approached significance for EAC (OR = 1.34, 95% CI 0.98-1.82). Allele
      and genotype frequencies at these loci were not significantly different between
      the RE group and controls. Although no significant association was observed
      between the disease groups at the -137 G/C locus, the -137G/-607C haplotype was
      associated with increased risk of BE (P = 0.006) with haplotype frequencies of
      55% in controls and 65% in BE. CONCLUSIONS: These data show a strong association
      of the IL-18RAP SNP rs917997 locus with BE and EAC and suggestive association of
      the Barrett's population with the IL-18-607 C/A promoter polymorphism. As both of
      these SNPs have been demonstrated as expression quantitative trait loci affecting
      expression of the respective genes, this strongly implicates IL-18 signaling in
      susceptibility to BE and EAC.

PMID- 22664471
TI  - The efficacy of cap-assisted colonoscopy in polyp detection and cecal intubation:
      a meta-analysis of randomized controlled trials.
AB  - OBJECTIVES: The role of cap-assisted colonoscopy (CAC) in polyp detection and
      cecal intubation is unclear. We conducted a meta-analysis to compare the efficacy
      of CAC vs. standard colonoscopy (SC). METHODS: Publications in English and non
      English literatures (OVID, MEDLINE, and EMBASE) and abstracts in major
      international conferences were searched for controlled trials comparing CAC and
      SC. Outcome measures included the proportion of patients with polyps or adenomas
      detected, cecal intubation rate, cecal intubation time, and total colonoscopy
      time. The statistical heterogeneity of trials was examined and the effects were
      pooled by random-effects model. The risk of bias was evaluated by the assessment
      tool from the Cochrane Handbook. Subgroup analyses were performed for possible
      clinical and methodological heterogeneities. RESULTS: From 2,358 citations, 16
      randomized controlled clinical trials were included consisting of 8,991 subjects
      (CAC: 4,501; SC: 4,490). Mean age of subjects was 61.0 years old and 60% were
      males. CAC detected a higher proportion of patients with polyp(s) (relative risk
      (RR): 1.08; 95% confidence interval (CI): 1.00-1.17) and reduced the cecal
      intubation time (mean difference: -0.64 min; 95% CI: -1.19 to -0.10). Cecal
      intubation rate (RR: 1.00; 95% CI: 0.99-1.02) and total colonoscopy time (mean
      difference: -0.97 min; 95% CI: -2.33 to 0.40) were comparable between the two
      groups. In subgroup analyses, a short cap (<=4 mm) was associated with improved
      polyp detection, whereas a long cap (>=7 mm) was associated with a shorter cecal
      intubation time. CONCLUSIONS: CAC demonstrated marginal benefit over SC for polyp
      detection and shortened the cecal intubation time.

PMID- 22664472
TI  - Challenges in design of translational nanocarriers.
AB  - Cancer drug delivery achieving high therapeutic efficacy and low side effects
      requires a nanocarrier to tightly retain the drug, efficiently reach the tumor,
      then quickly enter the tumor cells and release the drug. Furthermore, the
      nanocarrier intended for clinical applications should use materials safe as
      pharmaceutical excipients and its formulation (nanomedicine) should have good
      manufacture processes with scale-up ability. Thus, the challenge is to design
      safe, approvable, and easily scaled-up nanocarriers that simultaneously meet the
      two pairs of requirements of 'drug retention in circulation versus intracellular
      release' and 'stealthy in circulation versus sticky (cell-binding) in tumor' at
      the right places in order to deliver a cytosolic drug dose lethal to cancer cells
      with minimized side effects. Herein, we briefly review these elements aimed at
      promoting developments of translational nanocarriers.

PMID- 22664473
TI  - Tetraiodothyroacetic acid-tagged liposomes for enhanced delivery of anticancer
      drug to tumor tissue via integrin receptor.
AB  - Nanoparticles have demonstrated potential for promoting drug delivery to tumor
      sites and enhancing uptake. Here, we report tetraiodothyroacetic acid (tetrac) as
      a promising new targeting moiety for delivery of anticancer drugs to tumor
      tissues. Tetrac, an antagonist that blocks the binding of thyroid hormone to
      integrin alphavbeta3, was covalently linked to the activated end of pegylated
      lipid and used to formulate tetrac-tagged pegylated liposomes (TPL). After
      incubating with TPL for 9h, cellular accumulation efficiency into A375 human
      melanoma cells, which express integrin alphavbeta3 at high density, was high
      (98.5%+/- 0.5% of cells), whereas that in KB cells, which express integrin at a
      very low density, was much lower (35.1%+/- 4.5%). Molecular imaging revealed that
      TPL preferentially distributed to tumor tissues after systemic administration in
      mice, where as non-targeting pegylated liposomes were distributed to tumors at
      background levels. Treatment with the alkyl lysophospholipid anticancer drug
      edelfosine, encapsulated in TPL, significantly reduced the survival of A375 tumor
      cells compared to cells treated with edelfosine in pegylated liposomes or with
      lysophosphatidylcholine encapsulated in TPL. Moreover, intravenous administration
      of edelfosine in TPL significantly reduced the growth of tumors and prolonged the
      survival of A375-xenografted mice, providing 100% protection for up to 50 days
      and some protection until 66 days (0% survival endpoint). In contrast, no
      untreated mice or mice treated with edelfosine-loaded pegylated liposomes
      survived up to 50 or 48 days, respectively, after tumor inoculation. These
      results suggest the potential of tetrac as a new ligand moiety for enhancing the
      delivery of anticancer drug-loaded nanoparticles to tumors and enhancing the
      therapeutic efficacy of encapsulated anticancer drugs.

PMID- 22664474
TI  - Real-time monitoring of caspase cascade activation in living cells.
AB  - We introduce a simple, versatile and robust one-step technique that enables real
      time imaging of multiple intracellular caspase activities in living cells without
      the need for complicated synthetic protocols. Conventional fluorogenic probes or
      recently reported activatable probes have been designed to target various
      proteases but are limited to extracellular molecules. Only a few have been
      applied to image intracellular proteases in living cells because most of these
      probes have limited cell-permeability. Our platform does not need complicated
      synthetic processes; instead it involves a straightforward peptide synthesis and
      a simple mixing step with a commercial transfection agent. The transfection agent
      efficiently delivered the highly quenched fluorogenic probes, comprised of
      distinctive pairs of dyes and quenchers, to the initiator caspase-8 and the
      effector caspase-3 in MDA-MB-435 cells, allowing dual-imaging of the activities
      of both caspases during the apoptotic process induced by TNF-related apoptosis
      induced ligand (TRAIL). With the combination of multiple fluorogenic probes, this
      simple platform can be applied to multiplexed imaging of selected intracellular
      proteases to study apoptotic processes in pathologies or for cell-based high
      throughput screening systems for drug discovery.

PMID- 22664475
TI  - Henneguya cartilaginis n. sp. (Myxozoa: Myxosporea) in the head cartilage of masu
      salmon Oncorhynchus masou masou.
AB  - Henneguya cartilaginis n. sp. (Myxozoa: Myxosporea) is described from wild masu
      salmon Oncorhynchus masou masou in Hokkaido, Japan. H. cartilaginis n. sp.
      produced white cysts, up to 3mm in size, in the head of masu salmon. Infected
      fish exhibited cranial protrusion due to the cysts. Spores (11.4 * 8.6 MUm) of H.
      cartilaginis n. sp. were egg-shaped with the posterior end more pointed and
      possessed two caudal appendages (34.2 MUm average length). Histological
      observations revealed that large plasmodia possessing fine fibrous pseudopodia on
      the surface developed in the head cartilage. H. cartilaginis n. sp. resembles H.
      cerebralis, which was described from the cranial cartilage of Kosogol grayling
      Thymallus nigrescens in Mongolia. However, they were distinguishable by spore
      morphology. Molecular analysis of the 18S rDNA sequences indicated that H.
      cartilaginis n. sp. was most closely related to Henneguya zschokkei, H. nuesslini
      and H. salminicola of salmonid fish, with genetic similarities of 95.3%, 95.1%
      and 93.9%, respectively. Based on these differences in spore morphology,
      molecular data, the site of infection and geographical distribution, the present
      species is considered to be a new species.

PMID- 22664476
TI  - Association of serum adipocytokines with insulin resistance and liver injury in
      patients with chronic hepatitis C genotype 4.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection, especially genotypes 1 and 4, is
      associated with metabolic dysfunction. We investigated the potential role of
      adipocytokines in HCV-induced insulin resistance (IR) and modulating the
      progression of liver disease in patients with HCV-4. METHODS: Serum adiponectin,
      high molecular weight adiponectin, leptin, tumor necrosis factor-alpha,
      interluekin-6, homeostasis model for the assessment of insulin resistance, and
      M30 protein were measured in 147 HCV patients and 89 controls. Liver biopsies
      were evaluated for steatosis/inflammation/fibrosis, adiponectin mRNA/protein,
      AdipoR1/-R2 mRNA, and phosphoenolpyruvate carboxykinase gene expression, and
      adiponectin and CD95 immunoreactivity. RESULTS: CD95 immunoreactivity and
      adiponectin immunoreactivity were detected in all biopsies examined. Hepatic
      adiponectin immunostaining correlated positively with the intensity of hepatic
      CD95/Fas immunostaining (r=0.424; P=0.001). Hepatocyte CD95/Fas upregulation
      correlated with fibrosis, inflammation, and steatosis (r=0.52, P=0.0001; r=0.16,
      P=0.04; r=0.24, P=0.0001; respectively). Significant correlations of serum
      adiponectin, its receptors mRNA expression, hepatic adiponectin immunostaining,
      and mRNA transcription for phosphoenolpyruvate carboxykinase were identified with
      steatosis. A positive association between adiponectin and hepatic inflammation
      and fibrosis was identified. This correlation remained significant even after
      adjusting for age, sex, and body mass index. Among body mass index, age, and sex
      matched HCV-negative controls, patients with HCV-4 have higher serum leptin,
      adiponectin, and high molecular weight adiponectin, and these changes are
      independently correlated with IR. CONCLUSIONS: Our findings in patients with HCV
      4 show that adiponectin correlates with IR and with the different stages of liver
      injury. Steatosis upregulates hepatocyte CD95/Fas and thus increases apoptosis,
      which facilitates inflammation and fibrosis. These findings may provide potential
      clues for novel therapeutic intervention.

PMID- 22664477
TI  - RYR3 gene polymorphisms and cardiovascular disease outcomes in the context of
      antihypertensive treatment.
AB  - Nearly one-third of adults in the United States have hypertension, which is
      associated with increased cardiovascular disease (CVD) morbidity and mortality.
      The goal of antihypertensive pharmacogenetic research is to enhance understanding
      of drug response based on the interaction of individual genetic architecture and
      antihypertensive therapy to improve blood pressure control and ultimately prevent
      CVD outcomes. In the context of the Genetics of Hypertension Associated Treatment
      study and using a case-only design, we examined whether single-nucleotide
      polymorphisms in RYR3 interact with four classes of antihypertensive drugs,
      particularly the calcium channel blocker amlodipine versus other classes, to
      modify the risk of coronary heart disease (CHD; fatal CHD and non-fatal
      myocardial infarction combined) and heart failure (HF) in high-risk hypertensive
      individuals. RYR3 mediates the mobilization of stored Ca(+2) in cardiac and
      skeletal muscle to initiate muscle contraction. There was suggestive evidence of
      pharmacogenetic effects on HF, the strongest of which was for rs877087, with the
      smallest P-value=0.0005 for the codominant model when comparing amlodipine versus
      all other treatments. There were no pharmacogenetic effects observed for CHD. The
      findings reported here for the case-only analysis of the antihypertensive
      pharmacogenetic effect of RYR3 among 3058 CHD cases and 1940 HF cases show that a
      hypertensive patient's genetic profile may help predict which medication(s) might
      better lower CVD risk. 

PMID- 22664478
TI  - Intratumoral expression profiling of genes involved in angiogenesis in colorectal
      cancer patients treated with chemotherapy plus the VEGFR inhibitor PTK787/ZK
      222584 (vatalanib).
AB  - The phase III CONFIRM clinical trials demonstrated that metastatic colorectal
      cancer patients with elevated serum lactate dehydrogenase (LDH) had improved
      outcome when the vascular endothelial growth factor receptor (VEGFR) inhibitor
      PTK/ZK (Vatalanib) was added to FOLFOX4 chemotherapy. We investigated the
      hypothesis that high intratumoral expression of genes regulated by hypoxia
      inducible factor-1 alpha (HIF1alpha), namely LDHA, glucose transporter-1 (GLUT
      1), VEGFA, VEGFR1, and VEGFR2, were predictive of outcome in CONFIRM-1. Tumor
      tissue was isolated by laser-capture microdissection from 85 CONFIRM-1 tumor
      specimens; FOLFOX4/placebo n=42, FOLFOX4/PTK/ZK n=43. Gene expression was
      analyzed using quantitative RT-PCR. In univariate analyses, elevated mRNA
      expression of LDHA, GLUT-1, and VEGFR1 were associated with response to
      FOLFOX4/PTK/ZK. In univariate and multivariate analyses, elevated LDHA and VEGFR1
      mRNA levels were associated with improved progression-free survival in
      FOLFOX4/PTK/ZK patients. Furthermore, increased HIF1alpha and VEGFR2 mRNA levels
      were associated with decreased survival in FOLFOX/placebo patients but not in
      patients who received FOLFOX4/PTK/ZK. These are the first data suggesting
      intratumoral mRNA expression of genes involved in angiogenesis/HIF pathway may
      predict outcome to VEGFR-inhibitors. Biomarkers that assist in directing VEGFR
      inhibitors toward patients with an increased likelihood of benefit will improve
      the cost-effectiveness of these promising agents. 

PMID- 22664479
TI  - A genome-wide association study for irinotecan-related severe toxicities in
      patients with advanced non-small-cell lung cancer.
AB  - The identification of patients who are at high risk for irinotecan-related severe
      diarrhea and neutropenia is clinically important. We conducted the first genome
      wide association study (GWAS) to search for novel susceptibility genes for
      irinotecan-related severe toxicities, such as diarrhea and neutropenia, in non
      small-cell lung cancer (NSCLC) patients treated with irinotecan chemotherapy. The
      GWAS putatively identified 49 single-nucleotide polymorphisms (SNPs) associated
      with grade 3 diarrhea (G3D) and 32 SNPs associated with grade 4 neutropenia
      (G4N). In the replication series, the SNPs rs1517114 (C8orf34), rs1661167
      (FLJ41856) and rs2745761 (PLCB1) were confirmed as being associated with G3D,
      whereas rs11128347 (PDZRN3) and rs11979430 and rs7779029 (SEMAC3) were confirmed
      as being associated with G4N. The final imputation analysis of our GWAS and
      replication study showed significant overlaps of association signals within these
      novel variants. This GWAS screen, along with subsequent validation and imputation
      analysis, identified novel SNPs associated with irinotecan-related severe
      toxicities. 

PMID- 22664481
TI  - Structural biology of cytoplasmic and axonemal dyneins.
AB  - Dyneins are microtubule-based, ATP-driven motor proteins with six tandemly linked
      AAA+ domains, a long N-terminal tail and a coiled-coil stalk. Cytoplasmic dyneins
      function as individual homodimers and are responsible for minus-end-oriented
      transport along microtubules. Axonemal dyneins of flagella/cilia are anchored in
      arrays to peripheral microtubule doublets by their N-terminal tails, and generate
      sliding motions of adjacent microtubule doublets toward the plus end. The coiled
      coil stalk is responsible for communication between the AAA+ domains and the
      microtubule binding domain. A number of isoforms of axonemal dyneins are
      integrated to generate bending motion. In this article I will review recent
      structural studies and address the question as to how dyneins generate force and
      cause bending in flagella/cilia.

PMID- 22664480
TI  - Functional characterization of ABCC2 promoter polymorphisms and allele-specific
      expression.
AB  - Multidrug resistance protein 2 (MRP2, ABCC2) is an efflux membrane transporter
      highly expressed in liver, kidney and intestine with important physiological and
      pharmacological roles. The goal of this study was to investigate the functional
      significance of promoter region polymorphisms in ABCC2 and potential allele
      specific expression. Twelve polymorphisms in the 1.6 kb region upstream of the
      translation start site were identified by resequencing 247 DNA samples from
      ethnically diverse individuals. Luciferase reporter gene assays showed that ABCC2
      -24C>T both alone and as part of a common haplotype (-24C>T/-1019A>G/-1549G>A)
      increased promoter function 35% compared with the reference sequence (P<0.0001).
      No other common variants or haplotypes affected ABCC2 promoter activity. Allele
      specific expression was also investigated as a mechanism to explain reported
      associations of the synonymous ABCC2 3972C>T variant with pharmacokinetic
      phenotypes. In Caucasian liver samples (n=41) heterozygous for the 3972C>T
      polymorphism, the 3972C allele was preferentially transcribed relative to the
      3972T allele (P<0.0001). This allelic imbalance was particularly apparent in
      samples with haplotypes containing two or three promoter/untranslated region
      variants (-1549G>A, -1019A>G and -24C>T). The observed allelic imbalance was not
      associated with hepatic or renal ABCC2 mRNA expression. Additional mechanisms
      will need to be explored to account for the interindividual variation in ABCC2
      expression and MRP2 function. 

PMID- 22664482
TI  - Application of multielectrode array (MEA) chips for the evaluation of mixtures
      neurotoxicity.
AB  - Cortical neurons grown on multielectrode array (MEA) chips have been shown to be
      a valuable alternative method to study electrophysiological properties of the
      central nervous system neurons and to perform functional toxicological screening.
      Here we studied the effects of binary mixtures on neuronal networks cultured on
      MEAs. We have considered compounds with similar and different mode-of-action
      (MoA) to characterize and assess their combined effects. Individual and binary
      mixture dose-response curves based on spontaneous neuronal activity have been
      generated and the IC(50) has been considered as the end-point for neurotoxicity
      assessment. The two classical approaches of mixtures toxicity studies:
      concentration addition (CA) and independent action (IA) have been applied to
      compare calculated and experimental results. Nuclear magnetic resonance (NMR)
      spectroscopy has been employed to confirm no chemical reaction or complexation
      between mixtures components. The results suggest that both CA and IA are able to
      predict the toxicity of the mixture and that the combination of in vitro test
      methods with theoretical dose-response models has a strong potential as an
      alternative tool for the prediction of mixtures neurotoxicity.

PMID- 22664483
TI  - Triphenyltin impairs insulin secretion by decreasing glucose-induced NADP(H) and
      ATP production in hamster pancreatic beta-cells.
AB  - Oral administration of triphenyltin chloride (TPT) (6 mg/100g body weight)
      inhibits insulin secretion by decreasing glucose-induced cytoplasmic Ca(2+)
      concentration ([Ca(2+)](i)) in pancreatic beta-cells of the hamster. To test the
      possibility that the abnormal level of the [Ca(2+)](i) induced by TPT
      administration could be due to a defect in the metabolic signal of glucose in the
      beta-cells, we tested the effects of TPT administration on the glucose-induced
      NAD(P)H and ATP production, and on the changes of membrane potential and
      [Ca(2+)](i) by glucose and high K(+) in the beta-cells. The [Ca(2+)](i) was
      measured in islet cells loaded with fura-2. TPT administration significantly
      reduced the NAD(P)H and ATP production, the depolarization of plasma membrane,
      and insulin secretion by 15 mM glucose in islet cells. TPT administration also
      reduced the insulin secretion by 10mM dihydroxyacetone and glyceraldehyde.
      However, TPT administration did not affect the increase of [Ca(2+)](i) and the
      insulin secretion by 30 mMK(+) or 100 MUM tolbutamide, and the membrane potential
      by 30 mMK(+), and the insulin secretion by 10mM alpha-ketoisocaproic acid and
      0.5mM formycin A, an analog of ATP in the presence of 15 mM glucose. These
      results suggested that the pathogenesis of TPT-induced hyperglycemia in hamster
      involves the reduction of [Ca(2+)](i) and insulin secretion in response to K(ATP)
      channel-dependent depolarization, which is related to the decrease of NAD(P)H and
      ATP production in pancreatic islet cells after glucose metabolism.

PMID- 22664484
TI  - Effects of co-administration of dietary sodium arsenate and 2,3-dimercaptopropane
      1-sulfonic acid (DMPS) on the rat bladder epithelium.
AB  - Inorganic arsenic is a known human carcinogen, inducing tumors of the skin,
      urinary bladder and lung. It is metabolized to organic methylated arsenicals. 2,3
      Dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent, is capable of
      reducing pentavalent arsenicals to the trivalent state and binding to the
      trivalent species, and it has been used in the treatment of heavy metal poisoning
      in humans. Therefore, we investigated the ability of DMPS to inhibit the
      cytotoxicity and regenerative urothelial cell proliferation induced by arsenate
      administration in vivo. Female rats were treated for 4 weeks with 100 ppm As(V).
      DMPS (2800 ppm) co-administered in the diet significantly reduced the As(V)
      induced cytotoxicity of superficial cells detected by scanning electron
      microscopy (SEM), and the incidence of simple hyperplasia observed by light
      microscopy and the bromodeoxyuridine (BrdU) labeling index. It also reduced the
      total concentration of arsenicals in the urine and the methylation of arsenic.
      There were no differences in oxidative stress as assessed by immunohistochemical
      staining for 8-hydroxy-2'-deoxyguanosine (8OHdG) of the bladder urothelium. No
      differences were detected in urine sediments between groups. These data suggest
      that DMPS has the ability to inhibit both arsenate-induced acute toxicity and
      regenerative proliferation of the rat bladder epithelium, most likely by
      decreasing exposure of the urothelium to trivalent arsenicals excreted in the
      urine. These data provide additional evidence that the effects of arsenate
      exposure in vivo do not appear to be related to oxidative effects on dG in DNA.

PMID- 22664485
TI  - Effects of cypermethrin on the ligand-independent interaction between androgen
      receptor and steroid receptor coactivator-1.
AB  - The pyrethroid insecticide, cypermethrin has been considered as an environmental
      anti-androgen by interfering with the androgen receptor (AR) transactivation. In
      order to clarify the effects of cypermethrin on the ligand-independent
      interaction between the AR and SRC-1, the mammalian two-hybrid assay has been
      developed in the study. The AR N-terminal domain 1-660 amino acid residues were
      subcloned into the plasmid pVP16 to construct the vector pVP16-ARNTD. The SRC-1 C
      terminal domain 989-1240 amino acid residues were subcloned into the plasmid pM
      to construct the vector pM-SRC-1. The fusion vectors pVP16-ARNTD, pM-SRC-1 and
      the pG5CAT Reporter Vector were cotransfected into the CV-1 cells. The AR AF1
      interacted with SRC-1 in the absence of exogenous ligand 5alpha
      dihydrotestosterone (DHT). Furthermore, DHT did not enhance the interaction
      between AR AF-1 and SRC-1 at the concentrations from 10(-10)M to 10(-8)M.
      Cypermethrin inhibited the interaction between the AR AF1 and SRC-1, and the
      significant reduction was detected at the concentration of 10(-5)M. It is
      suggested that the interaction between the AR AF1 and SRC-1 is ligand
      independent. Cypermethrin inhibits AR activity by disrupting the ligand
      independent AR-SRC-1 interaction.

PMID- 22664486
TI  - Clinical efficacy of cardiac resynchronization therapy with an implantable
      defibrillator in a Japanese population: results of the MIRACLE-ICD outcome
      measured in Japanese indication (MOMIJI) study.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in reducing
      morbidity and mortality in systolic heart failure patients with cardiac
      dyssynchrony as demonstrated in studies with primarily Western populations.
      Although CRT devices with a defibrillator (CRT-D) became available in Japan since
      2006, their efficacy remains uncertain in Japanese patients. In this prospective,
      multicenter study, the efficacy of CRT-D therapy in an all-Japanese population
      was compared with the study conducted in the US, Multicenter InSync ICD
      Randomized Clinical Evaluation (MIRACLE-ICD). METHODS AND RESULTS: Ninety-three
      patients were evaluated according to the subject selection criteria of the
      MIRACLE-ICD study, and 80 patients were enrolled. Results at baseline and 6-month
      post-CRT-D implantation were compared in terms of composite clinical response
      (CCR) and other secondary endpoints. Quality of life (QOL) was assessed with a
      validated Japanese version of the Minnesota Living with Heart Failure
      questionnaire. CCR was improved in 55 patients (68.8%), unchanged in 14 (17.5%),
      and worsened in 11 patients (13.7%) (MIRACLE-ICD general phase: 62.0%, 13.4% and
      24.6%, respectively). Non-inferiority was verified by 1-sided test with 10%
      equivalence margin. QOL score improved significantly (50.0+/-26.2 vs. 23.6+/
      20.2, P<0.01). CONCLUSIONS: The MOMIJI study demonstrated that CRT-D
      effectiveness as assessed with CCR was non-inferior to the trials conducted
      outside Japan, thus suggesting that the benefits of CRT-D are similar between
      Japanese and non-Japanese patients.

PMID- 22664487
TI  - Modern angiogenic thermal therapy from the country of traditional thermal
      therapy.

PMID- 22664488
TI  - Loss of post-transcriptional regulation of DNMT3b by microRNAs: a possible
      molecular mechanism for the hypermethylation defect observed in a subset of
      breast cancer cell lines.
AB  - A hypermethylation defect associated with DNMT hyperactivity and DNMT3b
      overexpression characterizes a subset of breast cancers and breast cancer cell
      lines. We analyzed breast cancer cell lines for differential expression of
      regulatory miRs to determine if loss of miR-mediated post-transcriptional
      regulation of DNMT3b represents the molecular mechanism that governs the
      overexpression of DNMT3b that drives the hypermethylation defect in breast
      cancer. MicroRNAs (miRs) that regulate (miR-29a, miR-29b, miR-29c, miR-148a, miR
      148b) or are predicted (miR-26a, miR-26b, miR-203, miR-222) to regulate DNMT3b
      were examined among 10 hypermethylator and 6 non-hypermethylator breast cancer
      cell lines. Hypermethylator cell lines express diminished levels of miR-29c, miR
      148a, miR-148b, miR-26a, miR-26b, and miR-203 compared to non-hypermethylator
      cell lines. miR expression patterns correlate inversely with methylation
      sensitive gene expression (r=-0.66, p=0.0056) and directly with the methylation
      status of these genes (r=0.72, p=0.002). To determine the mechanistic role of
      specific miRs in the dysregulation of DNMT3b among breast cancer cell lines, miR
      levels were modulated by transfection of pre-miR precursors for miR-148b, miR
      26b, and miR-29c into hypermethylator cell lines (Hs578T, HCC1937, SUM185) and
      transfection of antagomirs directed against miR-148b, miR-26b, and miR-29c into
      non-hypermethylator cell lines (BT20, MDA-MB-415, MDA-MB-468). Antagomir-mediated
      knock-down of miR-148b, miR-29c, and miR-26b significantly increased DNMT3b mRNA
      in non-hypermethylator cell lines, and re-expression of miR-148b, miR-29c, and
      miR-26b following transfection of pre-miR precursors significantly reduced DNMT3b
      mRNA in hypermethylator cell lines. These findings strongly suggest that: i) post
      transcriptional regulation of DNMT3b is combinatorial, ii) diminished expression
      of regulatory miRs contributes to DNMT3b overexpression, iii) re-expression of
      regulatory miRs reduces DNMT3b mRNA levels in hypermethylator breast cancer cell
      lines, and iv) down-regulation of regulatory miRs increases DNMT3b mRNA levels in
      non-hypermethylator breast cancer cell lines. In conlcusion, the molecular
      mechanism governing the DNMT3b-mediated hypermethylation defect in breast cancer
      cell lines involves the loss of post-transcriptional regulation of DNMT3b by
      regulatory miRs.

PMID- 22664489
TI  - Health & ageing in international context.

PMID- 22664490
TI  - Elevated blood pressure & effectiveness of comprehensive risk reduction
      programme.

PMID- 22664491
TI  - In vitro tests for drug resistance in Plasmodium falciparum.

PMID- 22664492
TI  - Pneumonia in South-East Asia Region: public health perspective.
AB  - Globally, pneumonia is the leading cause of death in young children and burden of
      disease is disproportionately high in South-East Asia Region of WHO. This review
      article presents the current status of pneumonia disease burden, risk factors and
      the ability of health infrastructure to deal with the situation. Literature
      survey was done for the last 20 years and data from country offices were also
      collected. The estimated incidence of pneumonia in under five children is 0.36
      episodes per child, per year. Risk factors are malnutrition (40% in India),
      Indoor air pollution, non-breast feeding, chronic obstructive pulmonary disease,
      etc. Strengthening of health care delivery system for early detection and
      treatment and as well as minimization of preventable risk factors can avert a
      large proportion of death due to pneumonia.

PMID- 22664493
TI  - Association of CFTR gene mutation with bronchial asthma.
AB  - Mutation on both the copies of cystic fibrosis transmembrane conductance
      regulator (CFTR) gene results in cystic fibrosis (CF), which is a recessively
      transmitted genetic disorder. It is hypothesized that individuals heterozygous
      for CFTR gene mutation may develop obstructive pulmonary diseases like asthma.
      There is great heterogeneity in the phenotypic presentation and severity of CF
      lung disease. This could be due to genetic or environmental factors. Several
      modifier genes have been identified which may directly or indirectly interact
      with CFTR pathway and affect the severity of disease. This review article
      discusses the information related to the association of CFTR gene mutation with
      asthma. Association between CFTR gene mutation and asthma is still unclear.
      Report ranges from studies showing positive or protective association to those
      showing no association. Therefore, studies with sufficiently large sample size
      and detailed phenotype are required to define the potential contribution of CFTR
      in the pathogenesis of asthma.

PMID- 22664494
TI  - A pragmatic & translational approach of human biomonitoring to methyl isocyanate
      exposure in Bhopal.
AB  - Human biomonitoring has evolved beyond margins to ascertain exposure-response
      relationship in environmental associated human diseases. As occupational ailments
      continue to dominate global concerns, biomonitoring strategies have evolved
      better in terms of evaluating health risks associated with systemic uptake from
      chronic (long-term) environment exposures. Even though contributions of acute
      toxic exposures (short-term) towards initiation of disease processes have been
      gradually recognized, a comprehensive approach delineating mechanistic insights
      of such an implication remains elusive. Molecular biomonitoring in a strictly
      selected defined surviving cohort of the infamous Bhopal gas tragedy "as a
      model", could provide an unparallel opportunity to discern the long standing
      implications of acute exposures. Besides comprehending clinical significance of
      isocyanate toxicity, the results might provide a framework for understanding the
      molecular repercussions pertaining to a host of other such acute environmental
      exposures. The investigative strategy might also be helpful in identification of
      biomarkers with potential for translational research.

PMID- 22664495
TI  - Impact of comprehensive cardiovascular risk reduction programme on risk factor
      clustering associated with elevated blood pressure in an Indian industrial
      population.
AB  - BACKGROUND & OBJECTIVES: Cardiovascular risk factors clustering associated with
      blood pressure (BP) has not been studied in the Indian population. This study was
      aimed at assessing the clustering effect of cardiovascular risk factors with
      suboptimal BP in Indian population as also the impact of risk reduction
      interventions. METHODS: Data from 10543 individuals collected in a nation-wide
      surveillance programme in India were analysed. The burden of risk factors
      clustering with blood pressure and coronary heart disease (CHD) was assessed. The
      impact of a risk reduction programmme on risk factors clustering was
      prospectively studied in a sub-group. RESULTS: Mean age of participants was 40.9
      +/- 11.0 yr. A significant linear increase in number of risk factors with
      increasing blood pressure, irrespective of stratifying using different risk
      factor thresholds was observed. While hypertension occurred in isolation in 2.6
      per cent of the total population, co-existence of hypertension and >3 risk
      factors was observed in 12.3 per cent population. A comprehensive risk reduction
      programme significantly reduced the mean number of additional risk factors in the
      intervention population across the blood pressure groups, while it continued to
      be high in the control arm without interventions (both within group and between
      group P<0.001). The proportion of 'low risk phenotype' increased from 13.4 to
      19.9 per cent in the intervention population and it was decreased from 27.8 to
      10.6 per cent in the control population (P<0.001). The proportion of individuals
      with hypertension and three more risk factors decreased from 10.6 to 4.7 per cent
      in the intervention arm while it was increased from 13.3 to 17.8 per cent in the
      control arm (P<0.001). INTERPRETATION & CONCLUSIONS: Our findings showed that
      cardiovascular risk factors clustered together with elevated blood pressure and a
      risk reduction programme significantly reduced the risk factors burden.

PMID- 22664496
TI  - In vitro assessment of drug resistance in Plasmodium falciparum in five States of
      India.
AB  - BACKGROUND & OBJECTIVES: In vitro assays are an important tool to assess baseline
      sensitivity and monitor the drug response of Plasmodium falciparum over time and
      place and, therefore, can provide background information for the development and
      evaluation of drug policies. This study was aimed at determining the in vitro
      sensitivity of P. falciparum isolates to antimalarials. METHODS: The in vitro
      activity of 108 P. falciparum isolates obtained from five States of India was
      evaluated using WHO microtest (Mark III) to chloroquine, monodesethylamodiaquine,
      dihydroartesunate and mefloquine. Samples were collected from the States of
      Orissa, Jharkhand, Karnataka, Goa and Chhattisgarh from September 2007 to August
      2009. In addition, representative samples from different States of India
      cryopreserved and culture adapted in the Malaria Parasite Bank of National
      Institute of Malaria Research, New Delhi, were also evaluated. RESULTS: The
      proportion of isolates resistant to chloroquine and monodesethylamodiaquine was
      44.4 and 25 per cent, respectively. Of the 27 isolates resistant to
      monodesethylamodiaquine, 16 (59.3%) were cross-resistant to chloroquine. No
      isolate showed resistance to dihydroartesunate and mefloquine. Isolates from
      Orissa showed the highest degree of resistance to chloroquine and amodiaquine
      followed by Jharkhand. Forty two isolates were genotyped for pfcrt T76K
      chloroquine resistant mutation; mutations were seen in 38 (90.47%) isolates.
      INTERPRETATION & CONCLUSIONS: The Indian P. falciparum isolates showed a high
      degree of resistance to chloroquine followed by monodesethylamodiaquine. No
      resistance was recorded to mefloquine and dihydroartesunate.

PMID- 22664497
TI  - Associations of adipokines & insulin resistance with sex steroids in patients
      with breast cancer.
AB  - BACKGROUND & OBJECTIVES: Several studies have suggested an important, but
      conflicting and controversial role for adipose tissue mass in breast cancer risk.
      Factors such as insulin-like growth factors, sex steroids, adipokines and obesity
      related inflammatory markers have been postulated as potential effectors of the
      mechanisms by which obesity and associated metabolic disorders influence breast
      cancer risk. In this study we evaluated the associations between obesity indices,
      insulin resistance, circulating adipokines, sex steroids and breast cancer.
      METHODS: Fasting adiponectin, leptin, insulin resistance (homeostasis model
      assessment, HOMA-IR), testosterone, estradiol, sex hormone binding globulin
      (SHBG), LH and FSH were determined in 144 newly-diagnosed histologically
      confirmed breast cancer patients and 77 controls. Univariate and multivariate
      regression analyses were used to find the associations of these variables with
      each other, indices of obesity and with breast cancer. RESULTS: BMI, waist
      circumference, HOMA-IR and leptin were significantly (P<0.001) higher in patients
      than in controls. Adiponectin level was also significantly (P<0.05) higher in
      patients compared to controls. Adiponectin and leptin showed significant
      correlations with insulin and HOMA-IR but only adiponectin was significantly
      correlated with estradiol and SHBG. Logistic regression analyses showed that
      factors associated with breast cancer were BMI [OR (95% CI) =2.8 (1.4-5.5),
      P=0.004]; high levels of adiponectin [5.1 (2.2-11.5), P<0.001); hyperinsulinaemia
      [1.1 (1.0-1.1), P=0.01], leptin [3.1 (1.7-5.7), P<0.0001], estradiol [2.5 (1.3
      4.7), P=0.005] and testosterone [1.3 (1.03-1.7), P=0.03]. INTERPRETATION &
      CONCLUSIONS: Our findings confirm that adipokines, insulin resistance and sex
      steroids are associated with breast cancer. The paradoxical association of
      increased adiponectin with breast cancer is a novel finding that deserves further
      investigation.

PMID- 22664498
TI  - Role of homocysteine & MTHFR C677T gene polymorphism as risk factors for coronary
      artery disease in young Indians.
AB  - BACKGROUND & OBJECTIVES: Hyperhomocysteinaemia (HCA) either due to mutation of
      MTHFR gene or deficiency of vitamin B 12 and folic acid, has been reported as a
      risk factor for coronary artery disease (CAD). The present study was aimed to
      determine plasma homocysteine (Hcy) levels and to evaluate MTHFR C677T gene
      polymorphism as risk factors for CAD, and to study the role of Hcy in conjunction
      with a few other risk factors of CAD in young Indians. The effect of vitamin B12
      and folic acid supplements on the raised plasma Hcy levels in patients of CAD was
      also assessed. METHODS: The present study included 199 consecutive angiography
      confirmed CAD patients, <45 yr of age, without any other known pro- coagulant
      state and 200 age- and sex-matched healthy controls. Fasting blood samples were
      collected in EDTA and plasma Hcy was estimated by ELISA test and the MTHFR C677T
      polymorphism detection was carried out by PCR-RFLP method. RESULTS: Significant
      difference (P<0.001) was found between mean fasting levels of plasma Hcy in cases
      (22.14 +/- 10.62 MUmol/l) and controls (17.38 +/- 8.46 MUmol/l) with an Odds
      ratio as 1.93 (95% CI, 1.27-2.94). Levels of cholesterol, LDL, and triglycerides
      were significantly (P<0.001) higher in cases compared with controls.
      INTERPRETATION & CONCLUSIONS: Our study showed significant correlation between
      hyperhomocysteinaemia and coronary artery disease. Multivariate analysis by
      logistic regression of the various risk factors of CAD, found high levels of Hcy,
      cholesterol, LDL and low levels of HDL and smoking as independent predictors of
      CAD when all other factors were controlled. Significant post-treatment decrease
      found in HCA was easily modifiable by vitamin intervention irrespective to their
      CT or TT genotype of C677T MTHFR gene. Further studies to look at the plasma
      levels of folate and cobalamines and their association with Hcy are required to
      be done.

PMID- 22664500
TI  - Caution needed in using oral polio vaccine beyond the cold chain: vaccine vial
      monitors may be unreliable at high temperatures.
AB  - BACKGROUND & OBJECTIVES: Stabilized live attenuated oral polio vaccine (OPV) is
      used to immunize children up to the age of five years to prevent poliomyelitis.
      It is strongly advised that the cold-chain should be maintained until the vaccine
      is administered. It is assumed, that vaccine vial monitors (VVMs) are reliable at
      all temperatures. VVMs are tested at 37 degrees C and it is assumed that the
      labels reach discard point before vaccine potency drops to >0.6 log10. This study
      was undertaken to see if VVMs were reliable when exposed to high temperatures as
      can occur in field conditions in India. METHODS: Vaccine vials with VVMs were
      incubated (10 vials for each temperature) in an incubator at different
      temperatures at 37, 41, 45 and 49.5 degrees C. Time-lapse photographs of the VVMs
      on vials were taken hourly to look for their discard-point. RESULTS: At 37 and 41
      degrees C the VVMs worked well. At 45 degrees C, vaccine potency is known to drop
      to the discard level within 14 h whereas the VVM discard point was reached at 16
      h. At 49.5 degrees C the VVMs reached discard point at 9 h when these should have
      reached it at 3 h. CONCLUSION: Absolute reliance cannot be placed on VVM in
      situation where environmental temperatures are high. Caution is needed when using
      'outside the cold chain' (OCC) protocols.

PMID- 22664499
TI  - Serum interleukin-17 & nitric oxide levels in patients with primary Sjogren's
      syndrome.
AB  - BACKGROUND & OBJECTIVES: The interleukin (IL)-17 producing T-helper cells have
      been linked to pathogenesis of autoimmunity and mostly investigated in rheumatoid
      arthritis (RA). In this study we tested the IL-17 levels, as well as the levels
      of nitric oxide (NO) as possible IL-17-induced product, in patients with primary
      Sjogren's syndrome (pSS), an intricate and complex chronic autoimmune disorder of
      exocrine glands. METHODS: Serum IL-17 levels and nitrite concentrations
      determined in patients with pSS (n=30) were compared with the values obtained in
      patients with RA (n=10) and healthy controls (n=15). The values obtained for IL
      17 in pSS patients were also associated with the patients' clinical
      characteristics, particularly the rheumatoid factor (RF) and total antinuclear
      antibodies (tANA) levels. RESULTS: Serum concentrations of IL-17 were
      significantly (P<0.01) higher in patients with pSS (12.9 +/- 28.0 pg/ml) as
      compared to those obtained in healthy individuals (0.2 +/- 0.6 pg/ml), but not as
      high as the values obtained for the patients with RA (34.5 +/- 56.2 pg/ml). The
      mean IL-17 levels were significantly (P<0.05) higher in the pSS patients positive
      for rheumatoid factor (20.3 +/- 33.3 pg/ml) than in RF-negatives (0.3 +/- 0.6
      pg/ml). Mean serum concentrations of IL-17 were also higher in antinuclear
      antibody (ANA)-positive samples (19.8 +/- 33.5 pg/ml) in comparison to ANA
      negative sera (1.1 +/- 3.1 pg/ml) (P<0.05). The NO levels also showed elevated
      values in both pSS and RA patients, as compared to the healthy controls, since
      mean nitrite levels in patients with pSS and RA were 38.2 +/- 29.2 MUM and 41.7
      +/- 21.1 MUM, respectively, while those in healthy controls were significantly
      lower, at 19.2 +/- 10.5 MUM. INTERPRETATION & CONCLUSIONS: The findings of this
      study showed that there was increased IL-17 and NO production in patients with
      primary SS, especially if they had associated elevated rheumatoid factor and
      antinuclear antibody values.

PMID- 22664501
TI  - Evaluation of a rapid dipstick test for identifying cholera cases during the
      outbreak.
AB  - BACKGROUND & OBJECTIVES: Intermittent cholera outbreaks are major problem in many
      of the states of India. It is essential to identify cholera at the earliest for
      timely mobilization of public health responses and to abort the outbreaks. The
      present study was a part of a diarrhoeal outbreak investigation in Secunderabad,
      India, during May 2009 where the usefulness of Crystal VC rapid dipstick kit was
      assessed for detecting the aetiologic agent of the outbreak. METHODS: Stool
      specimens were collected from 15 hospitalized patients with acute watery
      diarrhoea and analyzed for detection of cholera vibrios using Crystal VC rapid
      dipstick kit and the usefulness of the kit was determined by comparative analysis
      of the same set of specimens using both microbiological and real-time PCR (RT
      PCR) based assays. RESULTS: Detection of Vibrio cholerae O1 from 10 of 15
      specimens was recorded using dipstick assay. Microbiological methods detected V.
      cholerae O1 positivity among 11 specimens. However, RT-PCR based assay showed all
      15 specimens positive for the presence of V. cholerae O1. In addition, the same
      assay showed that the pathogen load in the dipstick as well as RT-PCR positive
      specimens ranged from 10 6 colony forming units (cfu)/ml or more. INTERPRETATION
      & CONCLUSIONS: Crystal VC kit had the potential to identify cholera cases in 10
      min in field conditions without having good laboratory support. Therefore,
      dipstick kit may be considered as cholera detecting tool in diarrhoeal outbreak
      investigations. Specimens from clinically typical cholera cases, if negative by
      dipstick, should be reanalyzed by culture based methods.

PMID- 22664502
TI  - An outbreak of pandemic influenza A (H1N1) in Kolkata, West Bengal, India, 2010.
AB  - BACKGROUND & OBJECTIVES: An increased number of cases with influenza like illness
      (ILI) were reported in Greater Kolkata Metropolitan Area (GKMA) during July and
      August 2010. We investigated these cases to confirm the outbreak, describe the
      distribution of patients and propose control measures. METHODS: A suspected case
      of influenza like illness (ILI) was defined as acute onset of fever (>38 degrees
      C) with cough or sore throat and a confirmed case as ILI case with throat swab
      positive for influenza A (H1N1) on RT-PCR. The demographic and clinical details
      were collected from patients attending the swine flu OPD of Infectious Disease
      Hospital, Kolkata, during July 5 to August 16, 2010. RESULTS: Overall 440
      patients with ILI attended the swine flu OPD of Infectious Disease and Bengal
      General hospital during the study period, of which 129 were positive for
      influenza A (H1N1). Four patients died (case fatality ratio: 0.90%). Besides
      fever, common symptoms included cough (73%), running nose (54%), sore throat
      (43%), respiratory distress (25%) and diarrhoea (4%). Forty seven (11%) patients
      (including the four who died) had co-morbidities. The outbreak started on July
      10, peaked on July 24 and subsided by August 14, 2010. A total of 372 (85%)
      patients were from GKMA. Majority (n=168, 45%) of the cases from GKMA were from 6
      boroughs of Kolkata Municipal Areas. INTERPRETATION & CONCLUSIONS: An outbreak of
      influenza A (H1N1) occurred in Kolkata predominantly affecting young and middle
      aged population. State health authorities implemented several interventions to
      limit the outbreak including training of health care providers in case management
      and infection control, vaccination of health care workers, creation of isolation
      wards and administration of oseltamivir to ILI patients, and community health
      education about social distance and personal hygiene measures.

PMID- 22664503
TI  - Emergence of pandemic 2009 influenza A H1N1, India.
AB  - BACKGROUND & OBJECTIVES: Pandemic H1N1 caused deluge of cases from 74 countries
      and prompted World Health Organization to raise warning to phase 6. The present
      study was conducted on throat and nasal swab samples received and tested at
      National Centre for Disease Control, Delhi, India during 2009-2010 to collect
      epidemiological and clinical information on positive cases. METHODS: Throat and
      nasopharyngeal swabs from category C influenza A H1N1 patients during May 2009
      September 2010 along with their clinico-epidemiological details were collected
      from identified hospitals from Delhi and other States. Samples were tested by
      Real time reverse transcriptase PCR using primers and probes developed at CDC,
      Atlanta for four influenza target genes. RESULTS: A total of 33,751 samples, both
      throat and nasal swab samples from each patient were tested for H1N1 influenza
      virus, of which, 7943 (23.5%) were positive for pandemic influenza A H1N1 and
      3759 (11.1%) were positive for influenza A (seasonal flu). Maximum number of
      positive cases (N=2792, 35.1%) were from 20-39 yr age group, comprising 1790
      (22.5%) males and 1182 (14.8%) females. Only 2620 (33%) positive cases were close
      contact of influenza A H1N1 positive patient. Majority cases presented (N=2792,
      35.1%) with fever 7005 (88.1%), followed by 6133 cases (77.2%) exhibiting fever
      and cough, 377 (4.7%) complained of fever, cough, nasal catarrh and 362 (4.5%)
      cases had fever with shortness of breath. INTERPRETATION & CONCLUSIONS: The study
      showed a peak of cases of pandemic influenza A H1N1 in December 2009 and
      indicated predominance of H1N1 positive cases among 20-39 yr age group and among
      males compared to females.

PMID- 22664504
TI  - Serological evidence of rickettsial infections in Delhi.
AB  - BACKGROUND & OBJECTIVES: Rickettsial infections remain under-diagnosed due to
      lack of diagnostic facilities in developing world. Here we present our experience
      at National Centre for Disease Control, Delhi, about a serosurvey done in Delhi
      for rickettsial disease with easy to perform low cost, low expertise Weil Felix
      test. METHODS: On the basis of cut-off titre obtained in healthy population, Weil
      Felix test results were interpreted along with clinical data. Entomological
      investigation was also carried out in select areas of Delhi. Rodents were trapped
      from houses and gardens and vector mites were collected. RESULTS: When serum
      samples were collected during initial 5 yr period from patients with fever of
      unknown origin, seropositivity was 8.2 per cent whereas when rickettsial
      infection was kept as one of the differential diagnosis by clinicians
      seropositivity increased to 33.3 per cent. Rickettsial infections detected were
      scrub typhus (48.2%) followed by spotted fever group (27.5%) and typhus group
      (6.8%) during 2005-2009. In preliminary entomological survey vector mite
      Leptotombidium deliense was found on rodents. INTERPRETATION & CONCLUSIONS: Our
      findings showed that results of Weil Felix test should not be disregarded, rather
      clinically compatible cases should be treated to save lives.

PMID- 22664505
TI  - Evaluation of antimicrobial activity of certain combinations of antibiotics
      against in vitro Staphylococcus epidermidis biofilms.
AB  - BACKGROUND & OBJECTIVES: Staphylococcus epidermidis is the most common pathogen
      associated with infections of surgical implants and other prosthetic devices
      owing to its adhesion and biofilm-forming ability on biomaterials surfaces. The
      objective of this study was to compare susceptibilities of biofilm-grown cells to
      single antibiotic and in combination with others to identify those that were
      effective against S. epidermidis biofilms. METHODS: Biofilms were grown in the
      MBECTM assay system. The use of this methodology allowed a rapid testing of an
      array of antibiotics alone (eight) and in combination (25 double combinations).
      The antibacterial effect of all treatments tested was determined by colony
      forming units (cfu) enumeration method. RESULTS: The MBECTM assay system produced
      multiple and reproducible biofilms of S. epidermidis. Although none of the
      antibiotics tested have demonstrated an antimicrobial effect (log reduction >3)
      against all S. epidermidis isolates biofilms, but combinations containing
      rifampicin showed in general a broader spectrum namely rifampicin-gentamicin and
      rifampicin-clindamycin. Levofloxacin in combination with rifampicin showed a
      killing effect against three isolates but failed to attain a bactericidal action
      against the other two. INTERPRETATION & CONCLUSIONS: Our findings showed that
      rifampicin should be a part of any antibiotic therapy directed against S.
      epidermidis biofilms. However, the efficient antibiotics combination might be
      dependent on S. epidermidis isolate being tested.

PMID- 22664506
TI  - Restraint stress-induced central monoaminergic & oxidative changes in rats &
      their prevention by novel Ocimum sanctum compounds.
AB  - BACKGROUND & OBJECTIVES: Ocimum sanctum (OS) is known to possess various
      therapeutic properties. We have earlier isolated and characterized three OS
      compounds; Ocimarin, Ocimumoside A and Ocimumoside B. However, their role in
      modulating stress-induced central changes is unexplored. Thus, the present study
      was aimed to investigate the effect of these OS compounds on restraint stress
      (RS)-induced changes in the monoaminergic and antioxidant systems in the frontal
      cortex, striatum and hippocampus of rats. METHODS: RS was produced by
      immobilizing (restraining) the Sprague Dawley rats for a period of 2.5 h inside
      cylindrical steel tubes. The monoamine levels and the in vivo antioxidant status
      in brain regions were evaluated by HPLC-EC and spectrophotometric assays,
      respectively. RESULTS: RS significantly increased the dopamine levels in the
      frontal cortex and decreased in the striatum and hippocampus, and accompanied
      with selective increase of dopamine metabolites compared to the NS control group.
      The serotonin and its metabolite levels were significantly increased, while
      noradrenaline levels were decreased by RS in the three brain regions studied. The
      activities of superoxide dismutase and glutathione peroxidase in the frontal
      cortex and striatum were significantly increased by RS with decreased glutathione
      levels and increased lipid peroxidation. Pre-treatment with Ocimumoside A and B
      (40 mg/kg po) for a period of 3 days prevented the RS-induced changes with an
      efficacy similar to that of standard anti-stress (Panax quinquefolium; 100 mg/kg
      po) and antioxidant (Melatonin; 20 mg/kg ip) drugs, while, Ocimarin failed to
      modulate these changes. OS compounds per se had no effect on these parameters.
      INTERPRETATION & CONCLUSIONS: The present findings showed the anti-stress
      potential of Ocimumoside A and B in relation to their simultaneous modulatory
      effects on the central monoaminergic and antioxidant systems implicating their
      therapeutic importance in stress-related disorders. Further studies are required
      to understand the mechanism of action of these compounds.

PMID- 22664508
TI  - Need to confirm isoniazid susceptibility in Xpert MTB/RIF rifampin susceptible
      cases.

PMID- 22664507
TI  - Bioavailability enhancement studies of amoxicillin with Nigella.
AB  - BACKGROUND & OBJECTIVES: Nigella sativa Linn. is extensively used in the Indian
      diasporas as spice, which may interact with co-administered drugs and affect
      their intestinal availability. The purpose of this study was to investigate the
      effect of Nigella on bioavailability of amoxicillin in animal model. METHODS:
      Everted rat intestinal sacs were used for in vitro experiment to study the
      transfer of amoxicillin across the gut. Amoxicillin (6 mg/ml) was co-infused with
      3 and 6 mg of methanol and hexane extract of Nigella seeds separately. The amount
      of amoxicillin that traversed the gut was followed spectrophotometrically at 273
      nm. For in vivo studies Wistar albino rats were used. Amoxicillin (25 mg/kg, po)
      was co-administered with hexane extract of Nigella seeds (25 mg/kg, po). The
      amount of amoxicillin in rat plasma was determined by UPLC-MS/MS method. RESULTS:
      The in vitro studies both with methanol and hexane extracts of Nigella increased
      the permeation of amoxicillin significantly (P<0.001) as compared to control.
      Permeation was also found to be significantly higher for the hexane extract
      (P<0.001) in comparison to methanol extract at the same dose levels. In vivo
      experiments revealed that Cmax of amoxicillin in rat plasma when administered
      orally alone and in combination with hexane extract increased correspondingly
      from 4138.251 +/- 156.93 to 5995.045 +/- 196.28 ng/ml while as AUC 0->t increased
      from 8890.40 +/- 143.33 to 13483.46 +/- 152.45 ng/ml.h. INTERPRETATION &
      CONCLUSIONS: Nigella enhanced amoxicillin availability in both in vivo and in
      vitro studies. As the increase in bioavailability is attributed, in part, to
      enhanced diffusivity across intestine, our study indicated that Nigella increased
      intestinal absorption of amoxicillin.

PMID- 22664509
TI  - Association between drug resistance & production of biofilm in staphylococci.

PMID- 22664510
TI  - Prehypertension associated with dyslipidaemia in young adults - life-style &
      telomeres.

PMID- 22664511
TI  - Anti-nociceptive and anti-inflammatory activities of the Agastache mexicana
      extracts by using several experimental models in rodents.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Agastache mexicana is a plant that has long been
      used in large demand in Mexican folk medicine to treat pain, among others
      affections. Nevertheless, no scientific data confirming its use have been
      reported. The aim of this investigation was to examine the spectrum of
      antinociceptive activity of A. mexicana by using different experimental models of
      nociception in rodents. MATERIAL AND METHODS: Nociceptive activity was induced 30
      min post treatment of different doses of hexane, ethyl acetate and methanol
      extracts from A. mexicana aerial parts. The writhing test in mice, and the
      formalin and plantar tests as well as the pain-induced functional impairment
      assay in rats (PIFIR model) were the experimental nociceptive models used.
      Antinociceptive response of the organic extracts was compared to that observed
      with the analgesic drug tramadol. RESULTS: A. mexicana organic extracts produced
      a dose-dependent and significant inhibition of the abdominal constrictions caused
      by 1% acetic acid injection (i.p.) in mice. A maximal antinociceptive
      effectiveness obtained with tramadol was also observed with the administration of
      hexane and ethyl acetate extracts in comparison to less effectiveness obtained
      with the methanol extract. At the same range of doses, A. mexicana organic
      extracts inhibited the behavioral responses in both phases of the formalin pain
      test, in which a more intense effect was observed in the inflammatory phase than
      in the neurogenic stage. With regard to the plantar test and PIFIR model, a
      significant but not dose-dependent antinociceptive response was observed at
      specific doses that depended on the organic extract evaluated. CONCLUSION: The
      antinociceptive activity of A. mexicana aerial parts depends on the intensity of
      the painful stimulus induced and involves different kinds of constituents. Our
      present results reinforce the use of this species in traditional medicine and its
      utility for pain treatment mainly associated with inflammation.

PMID- 22664512
TI  - [Miccional dysfunction--functional and social disease].

PMID- 22664513
TI  - Immunohistochemical evaluation of estrogen and progesterone receptors of pre and
      post-neoadjuvant chemotherapy for breast cancer.
AB  - OBJECTIVE: To evaluate the immunoexpression of estrogen and progesterone
      receptors in biopsies and surgical specimens of patients with breast cancer
      before and after neoadjuvant chemotherapy and to correlate their changes with the
      pattern of response to chemotherapy and diagnosis of menopause. METHODS: We
      selected 47 patients with histological diagnosis of locally advanced primary
      breast carcinoma. For each patient there were two blocks: the biopsy specimen and
      surgical resection one. From these blocks hormone receptor expression was
      assessed by immunohistochemistry using the technique of streptoavidin-biotin
      immunoperoxidase and anti-ER and anti-PR primary antibodies. The statistical
      analysis used the Student's t test and the nonparametric Fisher's exact test,
      with significance level of 5%. RESULTS: Of the 47 patients, 30 showed positive
      immunostaining for hormone receptors. There was significant reduction in the
      levels of both estrogen and progesterone receptors and in their immunoreactivity.
      In 53.3% we observed changes in levels of estrogen receptor expression, 56.6% in
      the progesterone receptor, 26.6% in the immunoexpression of estrogen receptor
      immunoreactivity and 33.3% in the immunoreactivity of the progesterone receptor.
      There was no statistical correlation between the influence of the response to
      chemotherapy and the diagnosis of menopause in women with variation in the
      expression of hormone receptors. CONCLUSION: Neoadjuvant chemotherapy has
      significantly altered hormone receptor immunoreactivity in patients in the
      sample, reducing its positivity in tumor cells.

PMID- 22664514
TI  - Epidemiological analysis and use of rapid urease test in patients with perforated
      peptic ulcers.
AB  - OBJECTIVE: To analyze the epidemiological profile of patients with gastroduodenal
      ulcer perforation and verify if the presence of H. pylori in the peritoneal and
      intraluminal secretions of these patients can be assessed by rapid urease test.
      METHODS: We conducted a prospective, descriptive, cross-sectional study with data
      from patients in a hospital at a regional level, in patients with peptic ulcer.
      During surgery, we collected peritoneal fluid samples (in the vicinity of the
      perforation) and intraluminal secretion, sending them for culture and rapid
      urease test. RESULTS: Fourteen patients were analyzed. The average age was 41.06
      years, all men, Whites (71.4%), smokers (57.2%), BMI <30 (85.7%), with a history
      of dyspepsia (78.6%). Serology for H. pylori was positive in 84.6% of cases. The
      rapid urease test was positive in 78.6% of the samples of the digestive tract and
      42.8% of samples from the peritoneal cavity; 41.6% were positive at both sites,
      50% only in the digestive cavity and 8.4% only in the peritoneal cavity. Of the
      11 patients with positive serology for H. pylori, 100% were positive in at least
      one of the sites surveyed. CONCLUSION: It was found that the incidence was lower
      than expected. There is significant association between infection with H. pylori
      and the occurrence of perforation. The presence of this pathogen can be assessed
      both by serology and by the realization of the rapid urease test from fluid
      collected in the peritoneal cavity and the gastric / duodenal lumen.

PMID- 22664515
TI  - [Surgical reconstruction of post-cholecistectomy cicatricial biliary stenosis].
AB  - OBJECTIVE: To evaluate a series of cases of cicatricial stenosis of the biliary
      tract after cholecystectomy undergoing surgical reconstruction. METHODS: We
      conducted a retrospective study with 27 patients who underwent surgical
      reconstruction of the biliary tree for cicatricial stenosis. We analyzed the type
      of cholecystectomy that resulted in injury, age, gender, signs and symptoms, time
      of diagnosis, early or late, presence of previous surgery in an attempt to
      reconstruct the biliary tree, classification of stenosis and type of operation
      used for treatment of the injury. RESULTS: Twenty-six injuries occurred during a
      laparotomy and one during laparoscopy. Sixteen (59%) lesions were diagnosed
      intraoperatively or within the first postoperative day, seven (26%) havinh been
      submitted to reoperation at the local hospital, with poor results; nine patients
      in this group (33%) had no reoperation. Eleven patients (41%) had the classic
      form of cicatricial stenosis, without apparent intraoperative accidents and late
      development of biliary obstruction. All patients underwent Roux-en-Y hepatic
      jejunal anastomosis; in two cases the right and left hepatic ducts were implanted
      separately in the excluded jejunal loop. Twenty-six patients (96.3%) had no early
      complications; one patient had biliary fistula and died. One patient presented
      with stenosis recurrence, secondary cirrhosis and is awaiting liver
      transplantation. CONCLUSION: Most injuries were diagnosed during cholecystectomy
      within the first postoperative days; seven patients had been reoperated in an
      attempt to reconstruct the biliary tract. Roux-en-Y hepaticojejunostomy proved
      safe and effective in draining the bile duct in the short and long term.

PMID- 22664516
TI  - Employment of MELD score for the prediction of survival after liver
      transplantation.
AB  - OBJECTIVE: To assess the overall accuracy of the preoperative MELD score for
      predicting survival after liver transplantation (LT) and appraise medium-term (24
      months) predictors of survival. METHODS: We conducted a cross-sectional study
      including patients transplanted by the Department of General Surgery and Liver
      Transplantation of the Oswaldo Cruz University Hospital, University of
      Pernambuco, between July 15th, 2003 and July 14th, 2009. We used analysis of area
      under ROC (receiver operating characteristic) as a summary measure of the
      performance of the MELD score and assessed predictors of medium-term survival
      using univariate and multivariate analysis. RESULTS: The cumulative survival of
      three, six, 12 and 24 months of the 208 patients studied was 85.1%, 79.3%, 74.5%
      and 71.1%, respectively. The preoperative MELD score showed a low discriminatory
      power for predicting survival after TH. By univariate analysis, we identified
      intraoperative transfusion of red blood cells (p <0.001) and platelets (p =
      0.004) and type of venous hepatocaval anastomosis (p = 0.008) as significantly
      related to medium-term survival of the patients studied. However, by multivariate
      analysis only red blood cell transfusion was a significant independent predictor
      of outcome. CONCLUSION: The MELD score showed low overall accuracy for predicting
      post-transplant survival of patients studied, among which only intraoperative
      transfusion of red blood cells was identified as an independent predictor of
      survival in the medium term after TH.

PMID- 22664517
TI  - The use of double-J catheter decreases complications of retroperitoneoscopic
      ureterolithotomy.
AB  - OBJECTIVE: To evaluate the retroperitoneoscopic ureterolithotomy in the treatment
      of ureteral calculi and the need for double-J catheter to reduce the procedure
      related complications. METHODS: We conducted a retrospective study with 47
      patients submitted to retroperitoneoscopic ureterolithotomy, of which 31 were
      selected and divided into two groups: Group 1, whose patients did not have double
      J catheter placement, and Group 2, who underwent perioperative double-J catheter
      implantation. Data collected comprised pre-and post-operative excretory
      urography, operative time, postoperative analgesia, length of hospital stay and
      catheter removal. RESULTS: The groups were similar as for age and gender, degree
      of dilation of the urinary tract, position and average size of the calculi (Group
      1 = 15.5 +/- 6.6 mm, Group 2 = 16.3 +/- 6.1 mm). Operative time was also not
      significantly different (Group 1 = 130 +/- 40.3 min, Group 2 = 136.3 +/- 49.3
      min). Group 1 had six patients (37.5%) with early (four cases of urinary fistula)
      and late complications (one case of stenosis of the ureter, one case of
      functional exclusion of the operated kidney), while Group 2 had no complications.
      This difference was statistically significant (p = 0.011). CONCLUSION: The use of
      double-J catheter was associated with significantly fewer complications in
      retroperitoneoscopic ureterolithotomy. Surgical time, postoperative analgesia and
      length of stay were similar between groups with and without catheter.

PMID- 22664518
TI  - [Evaluation of changes made in the peri-operative care in patients submitted to
      elective abdominal surgery].
AB  - OBJECTIVE: To evaluate the results of the introduction of new measures to
      accelerate the postoperative recovery of patients undergoing elective abdominal
      surgery. METHODS: We observed 162 patients and interviewed them on two distinct
      periods: the first between October to December 2009 (n = 81) comprised patients
      who underwent conventional perioperative monitoring (pre-intervention) and the
      second between March and May 2010 (n = 81), formed by a new group of patients,
      submitted to the new protocol of perioperative monitoring. Data collection in the
      two periods occurred without the knowledge of the professionals in the service.
      The variables were: indication for preoperative nutritional support, duration of
      fasting, post-operative volume of hydration, use of catheters and drains, length
      of stay and postoperative morbidity. RESULTS: when comparing the two periods we
      observed a decrease of 2.5 hours in the time of preoperative fasting (p = 0.0002)
      in the post-intervention group. As for the reintroduction of oral diet, there was
      no difference between the two periods (p = 0.0007). When considering the patients
      without postoperative complications, there was a significantly decreased length
      of stay (p = 0.001325). There was a reduction of approximately 50% in antibiotic
      use in the post-intervention group (p = 0.00001). CONCLUSION: The adoption of
      multidisciplinary perioperative measures is feasible within our reality, and
      although there was no statistically significant changes in the present study, it
      may improve morbidity and reduce length of stay in general surgery.

PMID- 22664519
TI  - Evaluation of the capillaroscopy using endothelin-1 as a marker of endothelial
      activation in microvascular injury and cutaneous ulcerations.
AB  - OBJECTIVES: To evaluate the presence of ET-1 in patients with scleroderma and its
      correlation with the level of disease activity; to verify if the levels of
      endothelin are associated with the clinical profile and autoantibodies of
      scleroderma, and even if there is an association with microvascular injury
      detected by nailfold capillaroscopy. METHODS: A total of 74 patients, 37 patients
      with scleroderma, the remaining being controls, were subjected to measurement of
      ET-1 by ELISA. Patients with scleroderma were evaluated through a questionnaire
      about characteristics of the disease and determination of autoantibodies. Disease
      severity was defined by the criteria of Medsger and microvascular disease was
      accessed through nailfold capillaroscopy. RESULTS: Of the 37 patients with
      scleroderma, three (8.1%) were men and 34 (91.89%) women, with a mean age of
      48.97 +/- 13.36 years and mean disease duration of 42.54 +/- 13, 35. The amounts
      of ET-1 in the controls was 0.41 to 5.65 pg / ml (median of 2.26 pg / ml) and, in
      the scleroderma group, from 0.41 to 8.82 pg / ml (median, 0.41 pg / ml), with p =
      0.0007. There was no correlation with disease duration, patient age and the
      degree of skin involvement. No correlation was found between serum levels of ET-1
      and disease severity (p = 0.13). Higher levels of ET-1 were observed in the form
      of overlap (1.49 to 6.82 pg / ml). CONCLUSION: The levels of ET-1 in scleroderma
      were inferior to controls. There was no association of ET-1 levels with the
      variables studied.

PMID- 22664520
TI  - Effects of removal of the adventitia of the descending aorta and structural
      alterations in the tunica media in pigs.
AB  - OBJECTIVE: To investigate the effects of removal of the adventitia on the tunica
      media in a pig model. METHODS: The experiment was performed in eight pigs. The
      adventitia of the descending aorta was removed. Following euthanasia, at two,
      four, six and eight weeks, the aortic segment was removed. Next, slices of the
      aorta were stained with hematoxylin and eosin (HE) and Weigert-Van Gieson.
      RESULTS: After two weeks there was a slight cellular breakdown in the outer third
      of the media. After four weeks structural breakdown of elastic fibers was
      observed in the outer two thirds of the same layer. In six weeks, several areas
      of necrosis and almost complete disruption of elastic fibers were identified.
      Finally, after eight weeks, there was fibrosis of the entire wall with disruption
      of the internal elastic lamina. CONCLUSION: The removal of the adventitia leads
      to degeneration of the media, determining loss of the normal structure of the
      aortic wall that is variable in its location, intensity and shape, depending on
      the length and duration of the ischemic insult.

PMID- 22664521
TI  - Evaluation of the number of goblet cells in crypts of the colonic mucosa with and
      without fecal transit.
AB  - OBJECTIVE: To measure the thickness of the crypts and quantify the number of
      goblet cells of the colonic mucosa with and without intestinal transit, relating
      them to exclusion time. METHODS: Sixty Wistar rats were divided into three groups
      of 20 animals each according to the time of the final operation for the removal
      of the colon, in six, 12 or 18 weeks. In each group 15 animals underwent colonic
      exclusion by left colon proximal colostomy and distal mucous fistula, and five
      underwent only laparotomy (control). The colons with and without fecal stream
      were removed, processed and submitted to histological sections stained with
      hematoxylin-eosin. The height of the colonic crypts and the number of goblet
      cells were measured by computerized morphometry. We used the Student t test and
      Kruskal-Wallis test for comparison and analysis of variance, using a significance
      level of 5% (p <0.05). RESULTS: The height of the crypts decreased in segments
      without fecal stream (p =0.0001), reducing from six to 12 weeks of exclusion (p =
      0.0003), stabilizing thereafter. The number of goblet cells in the crypts was
      smaller in segments without transit after 12 and 18 weeks (p = 0.0001), but
      increased as the time of exclusion progressed (p = 0.04) CONCLUSION: The
      exclusion of intestinal transit decreases the thickness of the colonic crypts and
      the number of goblet cells in the segments without transit. There is an increased
      number of goblet cells in the course of time exclusion.

PMID- 22664522
TI  - [Digestive forms of Chagas disease and carcinogenesis: a study of association].
AB  - The authors analyze the relation between gastrointestinal carcinogenesis and
      Chagas disease, based on detailed review of the literature. To this end,
      epidemiological, experimental and human material pathology description studies
      have been selected. The article discusses the possibility of protection being
      afforded by not fully known morphokinetic cellular, immune and neuroendocrine
      factors that would be secondary to plexus degeneration. Also aspects related to
      the parasite-host interaction from the viewpoint of epithelial modulation of
      colonic mucosa and its antitumor implications are presented. Finally, it exposes
      the pathophysiological mechanism of esophageal cancer development in patients
      with mega-organ. In conclusion, chagasic colopathy, especially the intrinsic
      neuronal damage, is a study model that can contribute to the understanding of
      colorectal carcinogenesis.

PMID- 22664523
TI  - [Heterotopic ossification in incisional hernia sac].
AB  - The heterotopic ossification (HO) on abdominal scars is a rare but very
      unconfortable finding. It causes pain, induration and discomfort in the scar,
      leading patients to undergo reoperation. This report aims to describe a case of
      HO, and especially to call attention of surgeons to fibroblast transforming
      potential, once its close relationship with HO is undeniable. Therefore the
      surgeon should endeavor all atempts on good surgical practice to avoid HO
      occurrence. He should also associate pure tissue repair techniques to prosthetic
      management of incisional hernias, in the hope that patient's fibroblast grow
      factors can be offered to the wound healing as a biologically reinforcement of
      the repair.

PMID- 22664524
TI  - [Tolerance, courage and compassion: cardinal virtues of the surgeon].
AB  - Interactions among human beings are very complex. Using only an ethical code as
      reference to deal with moral conflicts is hardly ever enough. Responsibility
      ethics demand such a profound reflection as well as a discussion about human
      essence and its role in society. The responsibility of a surgeon is inherent in a
      profession based since its origin, not only on altruism and humanity, but also on
      compassion, courage and tolerance. The studies and the comprehension of these
      qualities as well as the transmission of these values to the students and to the
      surgery residents are essential for human education of these individuals. This
      essay offers to show that these essential virtues are strongly connected to the
      work the surgeon develops whereas his/her responsibility starts before the
      surgery - when one intends to act.

PMID- 22664525
TI  - Not complicated acute appendicitis in adults: clinical or surgical treatment?

PMID- 22664526
TI  - [Merkel cell carcinoma in lower end].
AB  - Merkel cells carcinoma is a rare cutaneous neoplasia. Studies revealed an
      increase in the occurrence from 0.15 to 0.44 cases for every 100.000 inhabitants
      between 1986 and 2001. Around 50% of the patients, eventually, develop systemic
      disease, being the most common sites the liver, the bones and the brain. The
      etiology is still unknown. The present study presents a new case of Merkel cells
      carcinoma in extremity, treated with local resection and adjuvant radiotherapy.

PMID- 22664527
TI  - Evaluation of pulmonary function in patients submitted to reduction mammaplasty.

PMID- 22664528
TI  - [Not Available].

PMID- 22664529
TI  - Diabetes: a Kit for increasing beta-cell function.

PMID- 22664530
TI  - Neuroendocrinology: new model for MEN1 risk prediction.

PMID- 22664531
TI  - Pituitary gland: ESRP1--a regulator of epithelial-mesenchymal transition in
      somatotroph adenomas?

PMID- 22664532
TI  - shRNA targeting Bmi1 impedes the self-renewal of cisplatin-enriched stem-like
      cells in human A549 cells.
AB  - It has been hypothesized that cancer stem-like cells are responsible for tumor
      recurrence following chemotherapy. Evidence on the mechanisms through which drug
      resistant stem-like cells recapitulate the tumor mass has not been definitively
      reported. Based on this information, we investigated the enrichment ability of a
      population of stem-like cells following treatment with cisplatin in human A549
      cells and focused on the molecular mechanisms regulating the self-renewal of stem
      like cells. A population of stem-like cells was enriched following cisplatin
      treatment and was defined phenotypically and functionally based on the expression
      of certain stem cell markers, sphere-forming ability, multipotent differentiation
      and induction of xenograft tumors in vivo. For various types of differentiated
      cells, Bmi1 has been reported to be important for cell proliferation and for the
      self-renewal of stem cells. The high expression of Bmi1 in cisplatin-enriched
      stem-like cells was shown using Q-PCR and western blotting; therefore, the role
      of Bmi1 was investigated in cisplatin-enriched stem-like cells by infecting
      cisplatin-enriched stem-like cells with Bmi1-targeted RNAi lentiviruses. Cell
      proliferation, tumor sphere formation and xenograft formation was reduced
      following knockdown of Bmi1. Based on our results, we propose that, after
      cisplatin treatment, Bmi1 is required for the self-renewal of stem-like cells
      that are important for the expansion of the stem-like cell pool in human A549
      cells and that targeting Bmi1 slows down the formation of tumors in vivo.

PMID- 22664533
TI  - Nutrient release from combustion residues of two contrasting herbaceous
      vegetation types.
AB  - Fire is a critical regulator of biogeochemical cycles in approximately 40% of the
      earth's land surface. However, little is known about nutrient release from
      combustion residues (ash and char) from herbaceous or grassland fires of varying
      intensity. Much of our knowledge in this area is derived from muffle furnace
      temperature gradient experiments. Therefore, we used two approaches (muffle and
      flame burning) to combust herbaceous biomass from contrasting nutrient level
      sites to estimate the forms and availability of nutrients after fire. Clear
      differences were measured in total and extractable nutrient concentrations in
      combustion residues of different plant types, with most carbon (C) and nitrogen
      (N) being volatilized (>99%), while P remained in high concentrations in the
      residues. Different combustion methods yielded contrasting results, where
      temperatures greatly affected nutrient quantity and form in muffle furnace
      residues, while relatively similar residues resulted from flame combustion at
      varying intensities. It was also found that only 5% of N and 50% of P remaining
      in flame combustion residues were extractable. Flame residues appeared to be
      composed of mixtures of materials (ash and char) created at low (<350  degrees C)
      muffle temperatures (extractable P forms), and high (>450  degrees C) muffle
      temperatures (pH, extractable potassium (K), and extractable NH(4)-N). We
      attribute dissimilar results of the combustion methods to heterogeneity of
      combustion (zones of low oxygen availability) and short duration (<300 s) of
      combustion characterizing natural fires in herbaceous, grassland systems. These
      results can be adapted to ecosystem level models to better predict nutrient
      changes that may occur after a fire event.

PMID- 22664534
TI  - Silver disinfection of Pseudomonas aeruginosa and E. coli in rooftop harvested
      rainwater for potable purposes.
AB  - Rainwater harvesting being an alternate source in water scarce areas is becoming
      a common practice. Catchment contact, however, deteriorates the quality of
      rainwater making it unfit for potable purposes. To improve the quality of
      harvested rainwater, silver was used as antimicrobial agent in this study.
      Rainwater samples were taken from underground storage tank of a rooftop rainwater
      harvesting system installed in one of the buildings at Seoul National University,
      Seoul, South Korea. The target microorganisms (MOs) were Pseudomonas aeruginosa
      and Escherichia coli which were measured by using plate count method and standard
      MPN method, respectively. The efficiency of silver disinfection was evaluated at
      concentrations, ranging from 0.01 to 0.1 mg/l; the safe limit approved by WHO.
      The experiments were performed for 168 h with different time intervals to
      evaluate the parameters including inactivation rate, residual effect of silver
      and re-growth in both MOs at lower (i.e. 0.01-0.04 mg/l) as well as the higher
      concentrations of silver (i.e. 0.08-0.1 mg/l). Results showed the re-growth in
      both MOs was only in the case of lower concentrations of silver. The possible
      reason of re-growth at these concentrations of silver may be the halting of
      bacterial cell replication process for some time without permanent damage. The
      kinetics of this study suggest that higher inactivation and long term residual
      effect towards both MOs can be achieved with the application of silver at 0.08
      mg/l or higher under safe limit.

PMID- 22664535
TI  - Influence of agricultural practice on trace metals in soils and vegetation in the
      water conservation area along the East River (Dongjiang River), South China.
AB  - Dongjiang (East River) is the key resource of potable water for the Pearl River
      Delta region, South China. Although industrial activities are limited in the
      water conservation area along this river, agriculture is very intensive. The
      present study evaluated trace metals in four soils under different cultivation.
      The total concentrations of trace metals decreased in the order orchard
      soil>vegetable soil>paddy soil>natural soil, reflecting decreasing inputs of
      agrochemicals to soils. Relatively high concentrations of Cd were recorded in the
      60-cm soil profiles. The (206)Pb/(207)Pb ratio in the above-ground tissues of
      plant was significantly lower than their corresponding soils. In combination with
      the low transfer factor of Pb from soil to plant shoots, atmospheric deposition
      is probably a major pathway for Pb to enter plant leaves. Regular monitoring on
      the soil quality in this area is recommended for the safety of water resource and
      agricultural products.

PMID- 22664536
TI  - Recent atmospheric dust deposition in an ombrotrophic peat bog in Great Hinggan
      Mountain, Northeast China.
AB  - Recent deposition of atmospheric soil dust (ASD) was studied using (210)Pb-dated
      Sphagnum-derived peat sequences from Great Hinggan Mountain in northeast China.
      Physicochemical indices of peat including dry bulk density, water content, ash
      content, total organic carbon and mass magnetic susceptibility were measured.
      Acid-insoluble concentration of lithogenic metals (Al, Ca, Fe, Mn, V and Ti) were
      measured using ICP-AES. The basic physicochemical properties were used to assess
      the peat trophic status and indicated that the sections above 45-60 cm are rain
      fed peat. A continuous record of ASD fluxes over the past 150 years was
      reconstructed based on the geochemical data obtained from the ombrotrophic zone,
      and the average input rate of ASD is 13.4-68.1 g m(-2) year(-1). The source of
      soil dust deposited in peat was dominated by the long-range transport of mineral
      aerosol from the drylands in north China and Mongolia. The temporal variation of
      ASD fluxes in the last 60 years coincides well with the meteorological records of
      dust storm frequency during 1954-2002 in north China. This suggests that the
      reconstructed sequence of atmospheric dust deposition is reliable and we can look
      back in time at the dust evolution before 1949. Dust storm events were observed
      occasionally in the late Qing dynasty, and their frequency and intensity were
      smaller than dust weather occurring in recent times. Four peaks of ASD fluxes
      were distinguished and correlated with the historical events at that time. This
      study presents the first atmospheric soil dust data in peat records in northeast
      China, and complements a global database of peat bog archives of atmospheric
      deposition. The results reflect the patterns of local environmental change over
      the past century in north China and will be helpful in formulating policies to
      achieve sustainable and healthy development.

PMID- 22664538
TI  - Exhaust emissions from a diesel power generator fuelled by waste cooking oil
      biodiesel.
AB  - The exhaust emissions from a diesel power generator operating with waste cooking
      oil biodiesel blends have been studied. Fuel blends with 25%, 50% and 75% of
      biodiesel concentration in diesel oil were tested, varying engine load from 0 to
      25 kW. The original engine settings for diesel oil operation were kept the same
      during the experiments with the biodiesel blends. The main physical-chemical
      characteristics of the fuel blends used were measured to help with the analysis
      of the emission results. The results show that the addition of biodiesel to the
      fuel increases oxides of nitrogen (NO(X)), carbon monoxide (CO) and hydrocarbon
      (HC) emissions. Carbon dioxide (CO(2)) and exhaust gas opacity were also
      increased with the use of biodiesel. Major increase of NO(X) was observed at low
      loads, while CO and HC were mainly increased at high loads. Using 50% of
      biodiesel in diesel oil, the average increase of CO(2), CO, HC and NO(X)
      throughout the load range investigated was 8.5%, 20.1%, 23.5% and 4.8%,
      respectively.

PMID- 22664537
TI  - Interspecific and intraspecific variation in selenium:mercury molar ratios in
      saltwater fish from the Aleutians: potential protection on mercury toxicity by
      selenium.
AB  - A number of factors affect the consumption risk from mercury in fish, including
      mercury levels, seasonal patterns of mercury concentrations, human consumption
      patterns, and sensitive populations (e.g. pregnant women, fetuses, young
      children, and yet unknown genetic factors). Recently the protective effects of
      selenium on methylmercury toxicity have been publicized, particularly for
      saltwater fish. We examine levels of mercury and selenium in several species of
      fish and seabirds from the Aleutians (Alaska), determine selenium:mercury molar
      ratios, and examine species-specific and individual variation in the ratios as a
      means of exploring the use of the ratio in risk assessment and risk management.
      Variation among species was similar for mercury and selenium. There was
      significant interspecific and intraspecific variation in selenium:mercury molar
      ratios for fish, and for birds. The mean selenium:mercury molar ratios for all
      fish and bird species were above 1, meaning there was an excess of selenium
      relative to mercury. It has been suggested that an excess of selenium confers
      some protective advantage for salt water fish, although the degree of excess
      necessary is unclear. The selenium:mercury molar ratio was significantly
      correlated negatively with total length for most fish species, but not for dolly
      varden. Some individuals of Pacific cod, yellow irish lord, rock greenling,
      Pacific halibut, dolly varden, and to a lesser extent, flathead sole, had
      selenium:mercury ratios below 1. No bird muscle had an excess of mercury (ratio
      below 1), and only glaucous-winged gull and pigeon guillemot had ratios between 1
      and 5. There was a great deal of variation in selenium:mercury molar ratios
      within fish species, and within bird species, making it difficult and impractical
      to use these ratios in risk assessment or management, for fish advisories, or for
      consumers, particularly given the difficulty of interpreting the ratios.

PMID- 22664539
TI  - Compost as a source of microbial isolates for the bioremediation of heavy metals:
      in vitro selection.
AB  - Heavy metal pollution has become a major environmental concern nowadays and the
      bioremediation of polluted habitats is an increasingly popular strategy due to
      both its efficiency and safety. A screening and selection protocol based on
      different composting processes was designed in order to isolate heavy metal
      resistant microorganisms. A collection of 51 microorganisms was obtained and most
      of them showed the capability to tolerate heavy metals in multi-polluted aqueous
      systems (Cd(II), Cr(VI), Ni, Pb, Zn(II)), as well as to remove them. The highest
      detoxification ratios were observed for Pb. Some of the isolates detoxifying more
      than a 90% of this metal, while the other metals were removed in a range between
      20% and 60%. The best isolates (Graphium putredinis, Fusarium solani, Fusarium
      sp. and Penicillium chrysogenum) were further assayed in order to determine the
      predominant removal mechanism and the potential use of their dead biomass as a
      biosorbent. Intracellular accumulation was the prevalent mechanism for most
      isolates and metals, with the exception of Ni. In this case, the proportion
      removed by extracellular adsorption was similar or even higher than that removed
      by intracellular accumulation. Thus, the efficiency of living cells was higher
      than that of dead biomass except in the case of Ni.

PMID- 22664540
TI  - Observation of elevated fungal tracers due to biomass burning in the Sichuan
      Basin at Chengdu City, China.
AB  - Fungal material (i.e., spores and fragments) is an important component of
      atmospheric aerosols. In order to examine the variability of fungal abundance in
      fine particles (PM(2.5)) during a biomass burning season, an intensive
      measurement campaign was conducted in the Sichuan Basin at Chengdu, a megacity in
      southwest China, in spring 2009. The aerosol samples were analyzed for
      carbonaceous species, including molecular tracers for biomass burning and fungal
      material, and water soluble ions. The results were interpreted with the help of
      principle component analysis, fire count maps, and the WRF model. Elevated
      concentrations of arabitol and mannitol were found with average concentrations of
      21.5+/-16.6 ng m(-3) and 43.9+/-19.3 ng m(-3), respectively, which were
      unexpectedly higher than those measured in fine particles in any other study
      reported previously. Even higher concentrations were observed in cases with
      simultaneous enhancements in the biomass burning tracers levoglucosan and K(+).
      In the case of influence by pollution plumes from biomass burning regions, the
      fungal tracer concentrations reached maximum values of 79.6 ng m(-3) and 121.8 ng
      m(-3), coinciding with peak levels of levoglucosan and K(+). Statistically
      significant correlations were found between the simultaneously observed fungal
      tracers (arabitol and mannitol) and biomass burning tracers (levoglucosan and
      K(+)), suggesting that these species were emitted by co-located sources, and
      hence the elevated fungal tracers were likely associated with biomass burning
      activities.

PMID- 22664541
TI  - Thorough investigations on indoor radon in Baita radon-prone area (Romania).
AB  - A comprehensive radon survey has been carried out in Baita radon-prone area,
      Transylvania, Romania, in 4 localities (Baita, Nucet, Finate, and Cimpani)
      situated in the vicinity of former Romanian uranium mines. Indoor radon
      concentrations have been measured in 1128 ground floor rooms and cellars of 303
      family houses by using CR-39 diffusion type radon detectors. The annual average
      of indoor radon concentration for Baita area was found to be 241+/-178 Bq m(-3),
      which is about two times higher than the average value of 126 Bq m(-3), computed
      for Romania. About 28% of investigated houses exceed the reference level of radon
      gas in dwellings of 300 Bq m(-3). The indoor radon measurements on each house
      have been carried out in several rooms simultaneously with the aim of obtaining a
      more detailed picture on the exposure to radon in the studied area. An analysis
      on the variability of radon levels among floors (floor-to-floor variation) and
      rooms (room-to-room variation) and also the influence of factors like the
      presence of cellar or the age of the building is presented. The coefficient of
      variation (CV) within ground floor rooms of the same house (room-to-room
      variation) ranged between 0.9 and 120.8%, with an arithmetic mean of 46.2%, a
      large variability among rooms within surveyed dwellings being clearly identified.
      The mean radon concentration in bedrooms without cellar was higher than in
      bedrooms above the cellar, the difference being statistically significant (t
      test, one tail, p<0.001, n=82). For houses built during 1960-1970 an increasing
      trend for radon levels was observed, but overall there was no significant
      difference in indoor radon concentrations by age of dwelling (one-way ANOVA test,
      p>0.05).

PMID- 22664542
TI  - Role of H2O2 in the photo-transformation of phenol in artificial and natural
      seawater.
AB  - In previous works, it was observed that phenol photo-induced transformation in
      natural seawater (NSW) mediated by natural photosensitizers occurs and leads to
      the formation of numerous hydroxylated, condensed, halogenated and
      nitroderivatives. Irradiation of NSW added with phenol and iron species had
      provided the enhanced formation of several halophenols, suggesting a central role
      played by iron species on the phenol halogenation in marine water. In this paper,
      we focus on hydrogen peroxide, another key photosensitizer, and its interaction
      with iron species. The ability of Fe(II)/Fe(III) and H(2)O(2) species to act as
      photo-sensitizers towards the transformation of organic compounds in seawater was
      investigated under simulated solar radiation. Light activation is necessary to
      induce the transformation of phenol, as no degradation occurs in the dark when
      either H(2)O(2) or iron/H(2)O(2) are initially added to artificial seawater
      (ASW). Fe(II) is easily transformed into Fe(III), assessing that a Fenton
      reaction (dark, Fe(II)/H(2)O(2)) does not take place in marine environment, in
      favour of a photo-activated reaction involving Fe(III) and H(2)O(2). When NSW is
      spiked with H(2)O(2) and Fe(III), halophenols' and nitrophenols' concentration
      decreases and completely disappears at high hydrogen peroxide concentration.
      Since Fe(II) and Fe(III) in spiked seawater induce an enhanced formation of
      haloderivatives, an excess of hydrogen peroxide act as scavenger towards the
      photo-produced chloro/bromo radicals, so hindering halogenation process in
      seawater. Hence, even if hydrogen peroxide efficiently induces the .OH radical
      formation, and could then promote the phenol phototransformation, nevertheless it
      is negligibly involved in the production of the intermediates formed during
      phenol photolysis in seawater, whose formation is necessarily linked to other
      photosensitizer species.

PMID- 22664543
TI  - Use of human perivascular stem cells for bone regeneration.
AB  - Human perivascular stem cells (PSCs) can be isolated in sufficient numbers from
      multiple tissues for purposes of skeletal tissue engineering. PSCs are a FACS
      sorted population of 'pericytes' (CD146+CD34-CD45-) and 'adventitial cells'
      (CD146-CD34+CD45-), each of which we have previously reported to have properties
      of mesenchymal stem cells. PSCs, like MSCs, are able to undergo osteogenic
      differentiation, as well as secrete pro-osteogenic cytokines. In the present
      protocol, we demonstrate the osteogenicity of PSCs in several animal models
      including a muscle pouch implantation in SCID (severe combined immunodeficient)
      mice, a SCID mouse calvarial defect and a femoral segmental defect (FSD) in
      athymic rats. The thigh muscle pouch model is used to assess ectopic bone
      formation. Calvarial defects are centered on the parietal bone and are standardly
      4 mm in diameter (critically sized). FSDs are bicortical and are stabilized with
      a polyethylene bar and K-wires. The FSD described is also a critical size defect,
      which does not significantly heal on its own. In contrast, if stem cells or
      growth factors are added to the defect site, significant bone regeneration can be
      appreciated. The overall goal of PSC xenografting is to demonstrate the
      osteogenic capability of this cell type in both ectopic and orthotopic bone
      regeneration models.

PMID- 22664546
TI  - Lovesickness: Erasistratus discovering the cause of Antiochus' disease.

PMID- 22664547
TI  - Cognitive functioning in prodromal psychosis: a meta-analysis.
AB  - CONTEXT: A substantial proportion of people at clinical high risk (HR) of
      psychosis will develop a psychotic disorder over time. Cognitive deficits may
      predate the onset of psychosis and may be useful as markers of increased
      vulnerability to illness. OBJECTIVE: To quantitatively examine the cognitive
      functioning in subjects at HR in the literature to date. DATA SOURCES: Electronic
      databases were searched until January 2011. All studies reporting cognitive
      performance in HR subjects were retrieved. STUDY SELECTION: Nineteen studies met
      the inclusion criteria, comprising a total of 1188 HR subjects and 1029 controls.
      DATA EXTRACTION: Neurocognitive functioning and social cognition as well as
      demographic, clinical, and methodological variables were extracted from each
      publication or obtained directly from its authors. DATA SYNTHESIS: Subjects at HR
      were impaired relative to controls on tests of general intelligence, executive
      function, verbal and visual memory, verbal fluency, attention and working memory,
      and social cognition. Processing speed domain was also affected, although the
      difference was not statistically significant. Later transition to psychosis was
      associated with even more marked deficits in the verbal fluency and memory
      domains. The studies included reported relatively homogeneous findings. There was
      no publication bias and a sensitivity analysis confirmed the robustness of the
      core results. CONCLUSIONS: The HR state for psychosis is associated with
      significant and widespread impairments in neurocognitive functioning and social
      cognition. Subsequent transition to psychosis is particularly associated with
      deficits in verbal fluency and memory functioning.

PMID- 22664548
TI  - Examination of the effectiveness of the Mental Health Environment of Care
      Checklist in reducing suicide on inpatient mental health units.
AB  - CONTEXT: Suicide is one of the leading causes of death in the United States.
      While suicides occurring during psychiatric hospitalization represent a very
      small proportion of the total number of suicides, these events are highly
      preventable owing to the controlled nature of the environment. Many methods have
      been proposed, but no interventions have been tested. OBJECTIVE: To evaluate the
      effect of identification and abatement of hazards on inpatient suicides in the
      Veterans Health Administration (VHA). DESIGN, SETTING, AND PATIENTS: The effect
      of implementation of a checklist (the Mental Health Environment of Care
      Checklist) and abatement process designed to remove suicide hazards from
      inpatient mental health units in all VHA hospitals was examined by measuring
      change in the rate of suicides before and after the intervention. INTERVENTION:
      Implementation of the Mental Health Environment of Care Checklist. MAIN OUTCOME
      MEASURE: The number of completed suicides on inpatient mental health units in VHA
      hospitals. RESULTS: Implementation of the Mental Health Environment of Care
      Checklist was associated with a reduction in the rate of completed inpatient
      suicide in VHA hospitals nationally. This reduction remained present when
      controlling for number of admissions (2.64 per 100 000 admissions before to 0.87
      per 100 000 admissions after implementation; P < .001) and bed days of care (2.08
      per 1 million bed days before to 0.79 per 1 million bed days after
      implementation; P < .001). CONCLUSIONS: Use of the Mental Health Environment of
      Care Checklist was associated with a substantial reduction in the inpatient
      suicide rate occurring on VHA mental health units. Use of the checklist in non
      VHA hospitals may be warranted.

PMID- 22664549
TI  - Positron emission tomography study of the effects of tryptophan depletion on
      brain serotonin(2) receptors in subjects recently remitted from major depression.
AB  - CONTEXT: Decreased brain serotonin (5-hydroxytryptamine) levels are considered to
      mediate depressive relapse induced by the tryptophan depletion paradigm. However,
      in patients who recently achieved remission from a major depressive episode with
      antidepressant treatment, only about half become depressed following tryptophan
      depletion. We hypothesized that downregulation of brain serotonin(2) receptors
      might be a compensatory mechanism that prevents some patients from becoming
      depressed with tryptophan depletion. OBJECTIVE: To assess, with use of positron
      emission tomography, whether brain serotonin(2) receptor downregulation occurs in
      patients with recently remitted depression who do not have depressive relapse,
      but not in those who become depressed, following tryptophan depletion. DESIGN:
      Each patient underwent 2 fluorine 18-labeled- setoperone positron emission
      tomography scans, one following a tryptophan depletion session and another
      following a control session. The order of scanning was counterbalanced. SETTING:
      Academic university hospital with imaging facilities. PARTICIPANTS: Seventeen
      patients in recent remission from a DSM-IV major depressive episode following
      treatment with selective serotonin reuptake inhibitors. MAIN OUTCOME MEASURES:
      Changes in brain serotonin(2) receptor binding. RESULTS: Of the 17 patients, 8
      (47%) became depressed during the tryptophan depletion session, and none
      developed depression during the control session. The depletion session was
      associated with a significant reduction in brain serotonin(2) receptor binding
      compared with the control session for all participants. A subgroup analysis
      revealed that the reduction in serotonin(2) receptor binding was significant only
      for the nondepressed group. CONCLUSION: Reduction in brain serotonin(2) receptors
      might be a potential compensatory mechanism to prevent tryptophan depletion
      induced depressive relapse.

PMID- 22664550
TI  - Basal cell carcinoma: stressful life events and the tumor environment.
AB  - CONTEXT: Child emotional maltreatment can result in lasting immune dysregulation
      that may be heightened in the context of more recent life stress. Basal cell
      carcinoma (BCC) is the most common skin cancer, and the immune system plays a
      prominent role in tumor appearance and progression. OBJECTIVE: To address
      associations among recent severe life events, childhood parental emotional
      maltreatment, depression, and messenger RNA (mRNA) coding for immune markers
      associated with BCC tumor progression and regression. DESIGN: We collected
      information about early parent-child experiences, severe life events in the past
      year as assessed by the Life Events and Difficulties Schedule, depression, and
      mRNA for immune markers associated with BCC tumor progression and regression from
      patients with BCC tumors. SETTING: University medical center. PARTICIPANTS:
      Ninety-one patients with BCC (ages, 23-92 years) who had a previous BCC tumor.
      MAIN OUTCOME MEASURES: The expression of 4 BCC tumor mRNA markers (CD25,
      CD3epsilon, intercellular adhesion molecule 1, and CD68) that have been linked to
      BCC tumor progression and regression were assessed in BCC tumor biopsy specimens.
      RESULTS: Both maternal and paternal emotional maltreatment interacted with the
      occurrence of severe life events to predict the local immune response to the
      tumor (adjusted P = .009 and P = .03, respectively). Among BCC patients who had
      experienced a severe life event within the past year, those who were emotionally
      maltreated by their mothers (P = .007) or fathers (P = .02) as children had a
      poorer immune response to the BCC tumor. Emotional maltreatment was unrelated to
      BCC immune responses among those who did not experience a severe life event.
      Depressive symptoms were not associated with the local tumor immune response.
      CONCLUSIONS: Troubled early parent-child relationships, in combination with a
      severe life event in the past year, predicted immune responses to a BCC tumor.
      The immunoreactivity observed in BCCs and the surrounding stroma reflects an anti
      tumor-specific immune response that can be altered by stress.

PMID- 22664551
TI  - Association of vascular factors with apathy in community-dwelling elderly
      individuals.
AB  - CONTEXT: Apathy in community-dwelling elderly individuals has been associated
      with a history of stroke and other cardiovascular disease. OBJECTIVE: To assess
      the relationship between symptoms of apathy and cardiovascular risk factors or
      disease (stroke or other) in a large sample of elderly people aged 70 to 78 years
      without depression or dementia. DESIGN: Cross-sectional data analysis within an
      ongoing cluster-randomized, open, multicenter trial. SETTING: The Netherlands,
      general community. PARTICIPANTS: We studied 3534 elderly individuals without
      dementia who were included in the Prevention of Dementia by Intensive Vascular
      Care trial. MAIN OUTCOME MEASURES: Symptoms of apathy, assessed with 3 items from
      the 15-item Geriatric Depression Scale, in participants with few or no depressive
      symptoms. RESULTS: The median age of participants was 74.3 years. Principal
      components analysis of the Geriatric Depression Scale confirmed a separate factor
      for the apathy items (Geriatric Depression Scale-3A). Two or more symptoms of
      apathy were present in 699 participants (19.9%), of whom 372 (53.2%) were without
      depressive symptoms (Geriatric Depression Scale-12D score <2). Ordinal regression
      analysis showed that increasing apathy in the absence of depressive symptoms was
      associated with a history of stroke (odds ratio, 1.79; 95% CI, 1.38-2.31) and
      cardiovascular disease other than stroke (1.28; 1.09-1.52). Exploratory analysis
      among 1889 participants free from stroke and other cardiovascular disease
      revealed an association between apathy score and the following cardiovascular
      risk factors: systolic blood pressure (P = .03), body mass index (P = .002), type
      2 diabetes mellitus (P = .07), and C-reactive protein (P < .001). CONCLUSIONS:
      Symptoms indicative of apathy are common in community-dwelling nondemented older
      people who are free from depression. The independent association of stroke, other
      cardiovascular disease, and cardiovascular risk factors with symptoms of apathy
      suggests a causal role of vascular factors.

PMID- 22664552
TI  - BRIDGE study warrants critique.

PMID- 22664554
TI  - Exit from the right ventricular outflow tract through the preferential conduction
      pathway in premature ventricular contractions originating from the pulmonary
      artery.

PMID- 22664555
TI  - Evaluation of metal pollution in fish and water collected from Gorgan coast of
      the Caspian Sea, Iran.
AB  - In this study, concentrations of zinc, chromium, cadmium and lead were determined
      in water and three species of fish sampled from 10 selected stations along Gorgan
      coast using atomic absorption spectrophotometery, summer 2009. Mean lead levels
      in water and fish samples (119.50 +/- 22.24 MUg/L and 113.80 +/- 33.11 MUg/kg)
      were significantly higher than that of cadmium and chromium (p < 0.05). Cyprinus
      carpio had highest metals content than Mugila auratus and Rutilus frisikutum. The
      evaluated metals values in water collected from Gomishan wetland (Pb, Cd, Cr and
      Zn values are 145.31 +/- 35.32, 120.46 +/- 11.44, 96.47 +/- 6.05 and 82.02 +/-
      34.37 MUg/L, respectively) were higher than the other sampling sites. The result
      is consistent with the findings accessed by evaluation of the metals in fish
      specimens. The metals concentrations in the fish and water samples were below the
      recommended limits. But, elevating levels of metals in water and fish made a
      serious concern about ecosystem and food chain contamination.

PMID- 22664556
TI  - Single incision laparoscopic cholecystectomy is associated with a higher bile
      duct injury rate: a review and a word of caution.
AB  - OBJECTIVE: To compare the incidence of bile duct injuries during single incision
      laparoscopic cholecystectomy (SILC) in relation to the accepted historic rate of
      0.4% to 0.5% for standard laparoscopic cholecystectomy (SLC). BACKGROUND:
      Technically, SILC is more challenging than SLC. The role and benefit of SILC in
      patient care has yet to be defined. Bile duct injuries have been reported in
      several series of SILC. METHOD: A comprehensive database search of MEDLINE,
      EMBASE, CINAHL, and PubMed Central was performed to generate all reported cases
      of SILC to present. The search was limited to reports of 20 or more patients
      based on current literature of existing SILC learning curves. Data were analyzed
      using the Student t test and chi analyses where appropriate. RESULTS: A total of
      76 candidate studies were identified; 45 studies met inclusion criteria for an
      aggregate total of 2626 patients. Most SILCs were performed in the absence of
      acute cholecystitis (90.6%). The aggregate complication rate was 4.2%, and
      complications were graded according to the Dindo-Clavien Classification System.
      Nineteen bile duct injuries were identified for a SILC-associated bile duct
      injury rate of 0.72%. CONCLUSIONS: There seems to be an increase in the rate of
      bile duct injuries during SILC when compared with historic rates during SLC.
      Because most SILCs are performed in optimal conditions, such as lack of acute
      inflammation, we urge caution in applying this technique to inflamed gallbladder
      pathology. Controlled trials are needed before conclusions are made regarding
      safety of SILC.

PMID- 22664557
TI  - Development and validation of a comprehensive curriculum to teach an advanced
      minimally invasive procedure: a randomized controlled trial.
AB  - OBJECTIVE: To develop and validate a comprehensive ex vivo training curriculum
      for laparoscopic colorectal surgery. BACKGROUND: Simulators have been shown to be
      viable systems for teaching technical skills outside the operating room; however,
      integration of simulation training into comprehensive curricula remains a major
      challenge in modern surgical education. Currently, no curricula have been
      described or validated for advanced laparoscopic procedures. METHODS: This
      prospective, single-blinded randomized controlled trial allocated 25 surgical
      residents to receive either conventional residency training or a comprehensive
      training curriculum for laparoscopic colorectal surgery. The curriculum consisted
      of proficiency-based psychomotor training on a virtual reality simulator,
      cognitive training, and participation in a cadaver lab. The primary outcome
      measure in this study was surgical performance in the operating room. All
      participants performed a laparoscopic right colectomy, which was video recorded
      and assessed using 2 previously validated assessment tools. Secondary outcome
      measures were knowledge relating to the execution of the procedure, assessed with
      a multiple-choice test, and technical performance on the simulator. RESULTS:
      Curricular-trained residents demonstrated superior performance in the operating
      room compared with conventionally trained residents (global score 16.0 [14.5
      18.0] versus 8.0 [6.0-14.5], P = 0.030; number of operative steps performed 16.0
      [12.5-17.5] versus 8.0 [6.0-14.5], P = 0.021; procedure-specific score 71.1 [54.4
      81.6] versus 51.1 [36.7-74.4], P = 0.122). Curricular-trained residents scored
      higher on the multiple-choice test (10 [9-11] versus 7.5 [5.3-7.5], P = 0.047),
      and outperformed conventionally trained residents in 7 of 8 tasks on the
      simulator. CONCLUSIONS: Participation in a comprehensive ex vivo training
      curriculum for laparoscopic colorectal surgery results in improved technical
      knowledge and improved performance in the operating room compared with
      conventional residency training. Reg. ID#NCT 01371136.

PMID- 22664558
TI  - An online spaced-education game for global continuing medical education: a
      randomized trial.
AB  - OBJECTIVE: To assess the efficacy of a "spaced-education" game as a method of
      continuing medical education (CME) among physicians across the globe. BACKGROUND:
      The efficacy of educational games for the CME has yet to be established. We
      created a novel online educational game by incorporating game mechanics into
      "spaced education" (SE), an evidence-based method of online CME. METHODS: This 34
      week randomized trial enrolled practicing urologists across the globe. The SE
      game consisted of 40 validated multiple-choice questions and explanations on
      urology clinical guidelines. Enrollees were randomized to 2 cohorts: cohort A
      physicians were sent 2 questions via an automated e-mail system every 2 days, and
      cohort B physicians were sent 4 questions every 4 days. Adaptive game mechanics
      re-sent the questions in 12 or 24 days if answered incorrectly and correctly,
      respectively. Questions expired if not answered on time (appointment dynamic).
      Physicians retired questions by answering each correctly twice-in-a-row
      (progression dynamic). Competition was fostered by posting relative performance
      among physicians. Main outcome measures were baseline scores (percentage of
      questions answered correctly upon initial presentation) and completion scores
      (percentage of questions retired). RESULTS: A total of 1470 physicians from 63
      countries enrolled. Median baseline score was 48% (interquartile range [IQR] 17)
      and, in multivariate analyses, was found to vary significantly by region (Cohen
      dmax = 0.31, P = 0.001) and age (dmax = 0.41, P < 0.001). Median completion score
      was 98% (IQR 25) and varied significantly by age (dmax = 0.21, P < 0.001) and
      American Board of Urology certification (d = 0.10, P = 0.033) but not by region
      (multivariate analyses). Question clustering reduced physicians' performance (d =
      0.43, P < 0.001). Seventy-six percent of enrollees (1111/1470) requested to
      participate in future SE games. CONCLUSIONS: An online SE game can substantially
      improve guidelines knowledge and is a well-accepted method of global CME
      delivery.

PMID- 22664559
TI  - Laparoscopy-assisted versus open distal gastrectomy for early gastric cancer:
      evidence from randomized and nonrandomized clinical trials.
AB  - OBJECTIVE: To evaluate the safety and efficacy of laparoscopy-assisted distal
      gastrectomy (LADG) in patients with early gastric cancer (EGC) to determine
      whether LADG is an acceptable alternative to open distal gastrectomy (ODG).
      BACKGROUND: LADG combined with less than D2 or D2 lymphadenectomy for EGC is
      still a controversial surgical intervention for its uncertain oncological safety
      and economic benefit. We conducted this systematic review and meta-analysis that
      included randomized control trials (RCTs) and non-RCTs of LADG versus ODG to
      evaluate whether the safety and efficacy of LADG in patients with EGC are
      equivalent to those of ODG. METHODS: A comprehensive search of PubMed, EMBASE,
      Cochrane Library, and China Knowledge Resource Integrated Database was performed.
      Eligible trials published between January 1, 1994, and December 31, 2010, were
      included in the study. Data synthesis and statistical analysis were carried out
      by RevMan 5.0 software. The quality of evidence was assessed by GRADEpro 3.2.2.
      RESULTS: Twenty-two studies with 3411 participants were included in this study.
      The mean number of lymph nodes retrieved in LADG was close to that retrieved in
      ODG (in the less than D2 resection: weighted mean difference [WMD] = -1.79; 95%
      confidence interval [95% CI], -5.78 to 2.19; P = 0.38; heterogeneity: P <
      0.00001, I = 98%; and in the D2 resection: WMD = -1.53; 95% CI, -3.56 to 0.51; P
      = 0.14; heterogeneity: P = 0.23, I = 26%). The overall postoperative morbidity
      was significantly less in LADG than in ODG (relative risk = 0.58; 95% CI, 0.46
      0.74; P < 0.00001; heterogeneity: P = 0.94, I = 0%). LADG reduced the
      intraoperative blood loss, postoperative analgesic consumption, and hospital
      duration, without increasing the total hospitalization costs and cancer
      recurrence rate. The long-term survival rate of patients undergoing LADG was
      similar to that of patients undergoing ODG. However, LADG was still a technically
      dependent and time-consuming procedure. Conversion rate of LADG was 0% to 2.94%.
      The reported reasons for conversion were bleeding, adhesion, and safety resection
      margin requirement. LIMITATIONS: : There were potential biases and significant
      heterogeneity in some clinical outcome measures in this study. Methodologically
      high-quality controlled clinical trials were sparse for this new surgical
      intervention. According to The Grading of Recommendations Assessment, Development
      and Evaluation approach, when assessing the safety and efficacy of LADG by
      comparing with those of ODG with the defined clinical outcomes in patients with
      EGC, the quality of the currently available clinical evidence was very low.
      CONCLUSIONS: LADG may be a technically feasible alternative for EGC when it is
      performed in experienced surgical centers in which patients undergoing LADG may
      benefit from the faster postoperative recovery. However, the currently available
      evidence cannot exclude the potential clinical benefits or harms, especially in
      the node-positive cases. Methodologically high-quality comparative studies are
      needed for further evaluation.

PMID- 22664560
TI  - Metabolic surgery for non-obese type 2 diabetes: incretins, adipocytokines, and
      insulin secretion/resistance changes in a 1-year interventional clinical
      controlled study.
AB  - OBJECTIVE: To compare duodenal-jejunal bypass (DJB) with standard medical care in
      nonobese patients with type 2 diabetes and evaluate surgically induced endocrine
      and metabolic changes. METHODS: Eighteen patients submitted to a DJB procedure
      met the following criteria: overweight, diabetes diagnosis less than 15 years,
      current insulin treatment, residual beta-cell function, and absence of
      autoimmunity. Patients who refused surgical treatment received standard medical
      care (control group). At baseline, 3, 6, and 12 months after surgery, insulin
      sensitivity and production of glucagon-like peptide-1 and glucose-insulinotropic
      polypeptide were assessed during a meal tolerance test. Fasting adipocytokines
      and dipeptidyl-peptidase-4 concentrations were measured. RESULTS: The mean age of
      the patients was 50 (5) years, time of diagnosis: 9 (2) years, time of insulin
      usage: 6 (5) months, fasting glucose: 9.9 (2.5) mmol/dL, and HbA1c (glycosylated
      hemoglobin) level: 8.9% (1.2%). Duodenal-jejunal bypass group showed greater
      reductions in fasting glucose (22% vs 6% in control group, P < 0.05) and daily
      insulin requirement (93% vs 15%, P < 0.01). Twelve patients from DJB group
      stopped using insulin and showed improvements in insulin sensitivity and beta
      cell function (P < 0.01), and reductions in glucose-insulinotropic polypeptide
      levels (P < 0.001), glucagon during the first 30 minutes after meal (P < 0.05),
      and leptin levels (P < 0.05). Dipeptidyl-peptidase-4 levels increased after
      surgery (P < 0.01), but glucagon-like peptide-1 levels did not change.
      CONCLUSIONS: Duodenal-jejunal bypass improved insulin sensitivity and beta-cell
      function and reduced glucose-insulinotropic polypeptide, leptin, and glucagon
      production. Hence, DJB resulted in better glycemic control and reduction in
      insulin requirement but DJB did not result in remission of diabetes.

PMID- 22664561
TI  - The development of a virtual reality training curriculum for colonoscopy.
AB  - OBJECTIVES: The development of a structured virtual reality (VR) training
      curriculum for colonoscopy using high-fidelity simulation. BACKGROUND:
      Colonoscopy requires detailed knowledge and technical skill. Changes to working
      practices in recent times have reduced the availability of traditional training
      opportunities. Much might, therefore, be achieved by applying novel technologies
      such as VR simulation to colonoscopy. Scientifically developed device-specific
      curricula aim to maximize the yield of laboratory-based training by focusing on
      validated modules and linking progression to the attainment of benchmarked
      proficiency criteria. METHODS: Fifty participants comprised of 30 novices (<10
      colonoscopies), 10 intermediates (100 to 500 colonoscopies), and 10 experienced
      (>500 colonoscopies) colonoscopists were recruited to participate. Surrogates of
      proficiency, such as number of procedures undertaken, determined prospective
      allocation to 1 of 3 groups (novice, intermediate, and experienced). Construct
      validity and learning value (comparison between groups and within groups
      respectively) for each task and metric on the chosen simulator model determined
      suitability for inclusion in the curriculum. RESULTS: Eight tasks in possession
      of construct validity and significant learning curves were included in the
      curriculum: 3 abstract tasks, 4 part-procedural tasks, and 1 procedural task. The
      whole-procedure task was valid for 11 metrics including the following: "time
      taken to complete the task" (1238, 343, and 293 s; P < 0.001) and "insertion
      length with embedded tip" (23.8, 3.6, and 4.9 cm; P = 0.005). Learning curves
      consistently plateaued at or beyond the ninth attempt. Valid metrics were used to
      define benchmarks, derived from the performance of the experienced cohort, for
      each included task. CONCLUSIONS: A comprehensive, stratified, benchmarked, whole
      procedure curriculum has been developed for a modern high-fidelity VR colonoscopy
      simulator.

PMID- 22664562
TI  - Pulmonary recurrence predominates after combined modality therapy for rectal
      cancer: an original retrospective study.
AB  - OBJECTIVE: To characterize patterns of recurrence in locally advanced rectal
      cancer treated with combined modality therapy (CMT): neoadjuvant chemoradiation +
      total mesorectal excision + adjuvant chemotherapy. METHODS: A total of 593
      consecutive rectal cancer patients (1998 to 2007) with locally advanced (stage
      II/III) disease (noted on endorectal ultrasound or magnetic resonance imaging)
      who received CMT were analyzed for patterns of recurrence. RESULTS: After median
      44-month follow-up (interquartile range, 25 to 64 months), 119 patients (20%)
      recurred: 105 distant, 7 local, 7 local and distant, and 112 distant-only
      recurrence. Ninety-three (78%) had single-organ recurrence, and 26 (22%) had
      multiple-organ recurrence. The most common site of distant recurrence was lung
      (69% of all patients with distant relapse); 20% had liver recurrence. Fourteen
      patients (2.4%) recurred locally. Pulmonary metastases were most commonly
      identified by computed tomographic scan versus abnormal positron emission
      tomographic (PET) scan or carcinoembryonic antigen (CEA). Risk factors associated
      with pulmonary recurrence were the following: pathologic stage, tumor distance
      from anal verge, lymphovascular or perineural invasion. Five-year freedom from
      pulmonary recurrence for patients with 0, 1, 2, or 3 risk factors was 99%, 90%,
      61%, and 42%, respectively. Thirty of 59 patents with pulmonary recurrence
      underwent lung metastasectomy; 3-year freedom from recurrence was 37%.
      CONCLUSIONS: Unlike colon cancer, which most frequently recurs in the liver,
      locally advanced rectal cancer treated with CMT relapses most frequently in the
      lung. Pulmonary metastasis was associated with advanced pathologic stage, low
      lying tumor, lymphovascular invasion, or perineural invasion. Confirmation of
      pulmonary metastasis usually requires serial imaging because metastases are often
      small when initially detected, well below the resolution of PET, and not
      necessarily associated with elevated CEA. Individualized risk-based surveillance
      strategies are recommended in this patient population.

PMID- 22664565
TI  - Randomized controlled split-mouth clinical trial of direct laminate veneers with
      two micro-hybrid resin composites.
AB  - OBJECTIVES: This randomized, split-mouth clinical study evaluated the survival
      rate of direct laminate veneers made of two resin-composite materials. METHODS: A
      total of 23 patients (mean age: 52.4 years old) received 96 direct composite
      laminate veneers using two micro-hybrid composites in combination with two
      adhesive resins (Ena-Bond-Enamel HFO: n=48, Clearfil SE Bond-Miris2: n=48).
      Enamel was selectively etched with 38% H(3)PO(4) for 30s, rinsed 30s and the
      corresponding adhesive resin was applied accordingly. Existing resin composite
      restorations in good conditions (small or big) were not removed but conditioned
      using silica coating (CoJet) and silanized (ESPE-Sil). Restorations were
      evaluated at baseline and thereafter every 6 months. Additional qualitative
      analysis was performed using modified USPHS criteria. RESULTS: Mean observation
      period was 41.3 months. Altogether, 12 absolute failures were observed [survival
      rate: 87.5%] (Kaplan-Meier). The survival rates with the two resin composites did
      not show significant differences [Enamel HFO: 81.2%, Miris2: 93.8%] (p>0.05). The
      presence of existing composite restorations on the prepared teeth did not affect
      the survival rate significantly (intact teeth: 100%, small restorations: 90.6%,
      big restorations: 82.7%) (p>0.05). Surface roughness and marginal discolouration
      were the main qualitative deteriorations observed until the final recall.
      Secondary caries and endodontic complications did not occur in any of the teeth.
      CONCLUSION: Early findings of this clinical study with the two micro-hybrid
      composite laminate veneers showed similar survival rate and their clinical
      performance was not significantly influenced when bonded onto intact teeth or
      onto teeth with existing restorations with the protocol applied.

PMID- 22664566
TI  - Conventional caries removal and sealed caries in permanent teeth: a
      microbiological evaluation.
AB  - OBJECTIVES: The aim of this study was to compare microbiological infection after
      conventional carious dentine removal with incomplete carious dentine removal and
      sealing. METHODS: Eighty-seven patients (12-50 years of age) under treatment at
      the Dental Clinics of the Federal University of Rio Grande do Sul (UFRGS),
      Brazil, participated in the study. The patients presented 90 posterior permanent
      teeth with primary caries. The lesions were coronal, active, and reached at least
      the middle third of the dentine. None of the teeth exhibited spontaneous pain,
      sensitivity to percussion or apical pathology (detected through radiographic
      exams). Pulp sensibility was confirmed by the cold test. The lesions were divided
      into 2 experimental groups: complete caries removal (CCR) based on hardness
      criteria (n=60 lesions) and incomplete caries removal (ICR) and sealing (n=32
      lesions). Microbiological samples were obtained from the initial demineralized
      dentine, after CCR and after ICR-Seal. RESULTS: The number of anaerobic and
      aerobic bacteria, lactobacilli, and mutans streptococci decreased at the end of
      treatment (p<0.05). Significantly less anaerobic bacteria (p<0.01), aerobic
      bacteria (p=0.02), and mutans streptococci (p<0.01) growth was observed after ICR
      Seal compared to CCR. The difference in lactobacilli was insignificant (p=0.08).
      The amount of bacteria detected after conventional caries removal was higher than
      that which remained in sealed caries lesions. CONCLUSIONS: The results suggest it
      is not necessary to remove all carious dentine before the restoration is placed
      because over time, sealing of carious dentine results in lower levels of
      infection than traditional dentine caries removal. CLINICAL SIGNIFICANCE: The
      results of this study indicate that sealed carious dentine was less infected than
      the remaining dentine left after conventional caries removal and sealing. Our
      results support treatment of deep carious lesions in one session with incomplete
      removal of carious dentine.

PMID- 22664567
TI  - Lateralization of responses to vibrissal stimulation: connectivity and
      information integration in the rat sensory-motor cortex assessed with fMRI.
AB  - Rats move their whiskers or vibrissae to gain sensory information about the world
      surrounding them. A single whisker can work as an independent detector but normal
      whisking involves the use of several vibrissae in a bilateral fashion. Here we
      used blood oxygen level dependent (BOLD) contrast to acquire functional magnetic
      resonance images (fMRI) of the rat brain activity during uni- and bilateral
      whisker stimulations with different timing schemes under Isoflurane anesthesia.
      Experiments were performed to assess the integration of bilateral information
      produced by normal whisking behavior. First, we showed that it was possible to
      obtain BOLD whisker activations using Isoflurane harmless for the animals and
      thus allowing for future repetitive/longitudinal studies. Second, we obtained
      different BOLD activation patterns depending on the number of stimulated whiskers
      and timing of the stimulation scheme. Third, we found lateralization of BOLD
      activations in the somatosensory-motor cortex. It manifested itself in
      considerably larger activations in the right hemisphere during equal bilateral
      whisker stimulation. Fourth, we found Granger Causality Analysis (GCA) to be a
      useful tool in information integration analysis, as it reproduced the stimulus
      specific Cross-correlation Analysis results. Both analyses showed that the amount
      of whiskers stimulated and the timing of stimulation lead to specific dynamic
      connectivity patterns. Finally, by adding directionality information GCA revealed
      meaningful lateralization of information processing in the rat whisker system
      consistent with the observed BOLD activation patterns.

PMID- 22664568
TI  - fMRI response in the medial prefrontal cortex predicts cocaine but not sucrose
      self-administration history.
AB  - Repeated cocaine exposure induces long-lasting neuroadaptations that alter
      subsequent responsiveness to the drug. However, systems-level investigation of
      these neuroplastic consequences is limited. We employed a rodent model of drug
      addiction to investigate neuroadaptations associated with prolonged forced
      abstinence after long-term cocaine self-administration (SA). Since natural
      rewards also activate the mesolimbic reward system in a partially overlapping
      fashion as cocaine, our design also included a sucrose SA group. Rats were
      trained to self-administer cocaine or sucrose using a fixed-ratio one, long
      access schedule (6 h/day for 20 days). A third group of naive, sedentary rats
      served as a negative control. After 30 days of abstinence, the reactivity of the
      reward system was assessed with functional magnetic resonance imaging (fMRI)
      following an intravenous cocaine injection challenge. A strong positive fMRI
      response, as measured by fractional cerebral blood volume changes relative to
      baseline (CBV%), was seen in the sedentary control group in such cortico-limbic
      regions as medial prefrontal cortex and anterior cingulate cortex. In contrast,
      both the cocaine and sucrose SA groups demonstrated a very similar initial
      negative fMRI response followed by an attenuated positive response. The magnitude
      of the mPFC response was significantly correlated with the total amount of
      reinforcer intake during the training sessions for the cocaine SA but not for the
      sucrose SA group. Given that the two SA groups had identical histories of operant
      training and handling, this region-specific group difference revealed by
      regression analysis may reflect the development of neuroadaptive mechanisms
      specifically related to the emergence of addiction-like behavior that occurs only
      in cocaine SA animals.

PMID- 22664570
TI  - Detailed studies of growth hormone secretion in cystinosis patients.
AB  - BACKGROUND: Cystinosis is an autosomal recessive disorder characterized by
      intralysosomal cystine accumulation. Growth retardation is more pronounced in
      cystinosis than in other chronic kidney diseases and is mostly not corrected by
      cysteamine. METHODS: Growth was evaluated in nine cystinosis patients, all
      treated with cysteamine, both after cysteamine and recombinant human growth
      hormone (rhGH) therapy initiation. Growth hormone (GH) secretion was studied by
      nocturnal GH measurements in four of nine patients and by glucagon test in four
      of nine patients. RESULTS: RhGH was administered to seven of nine patients. At
      rhGH initiation, height was below -2 SDS in five of seven patients, final height
      was above -2 SDS in six of seven. In two patients not treated with rhGH, final
      height remained below -4 SDS despite cysteamine treatment being started at the
      age of 6.1 and 8.1 years, respectively. Nocturnal GH secretion was normal in all
      patients. Glucagon tests revealed GH deficiency in one patient; two of four
      patients had abnormal GH peak timing. CONCLUSIONS: We present the first reported
      case of GH deficiency in cystinosis. Although no overt GH deficiency was detected
      in other patients, abnormal GH peak timing can indicate a subclinical GH
      secretion problem. RhGH significantly improved growth in cystinosis patients and
      should be initiated early in life.

PMID- 22664569
TI  - Quantitative MR imaging of two-pool magnetization transfer model parameters in
      myelin mutant shaking pup.
AB  - Magnetization transfer (MT) imaging quantitatively assesses cerebral white matter
      disease through its sensitivity to macromolecule-bound protons including those
      associated with myelin proteins and lipid bilayers. However, traditional MT
      contrast measured by the MT ratio (MTR) lacks pathologic specificity as
      demyelination, axon loss, inflammation and edema all impact MTR, directly and/or
      indirectly through multiple covariances among imaging parameters (particularly
      MTR with T(1)) and tissue features (e.g. axon loss with demyelination). In this
      study, more complex modeling of MT phenomena ("quantitative" MT or qMT) was
      applied to a less complex disease model (the myelin mutant shaking [sh] pup,
      featuring hypomyelination but neither inflammation nor axon loss) in order to
      eliminate the covariances on both sides of the MR-pathology "equation" and
      characterize these important relationships free from the usual confounds. qMT
      measurements were acquired longitudinally in 6 sh pups and 4 age-matched controls
      ranging from 3 to 21 months of age and compared with histology. The qMT
      parameter, bound pool fraction (f), was the most distinctive between diseased and
      control animals; both f and longitudinal relaxation rate R(1) tracked myelination
      with normal aging, whereas MTR did not--presumably owing to counterbalancing MT
      and R(1) effects. qMT imaging provides a more accurate and potentially more
      specific non-invasive tissue characterization.

PMID- 22664571
TI  - Combination therapy of atorvastatin and amlodipine inhibits sympathetic nervous
      system activation and improves cognitive function in hypertensive rats.
AB  - BACKGROUND: A previous study has demonstrated that orally administered
      atorvastatin reduces sympathetic nervous system (SNS) activation via an anti
      oxidant in the rostral ventrolateral medulla (RVLM) of hypertensive rats, whereas
      amlodipine did not. Furthermore, several previous reports have suggested that
      atorvastatin or amlodipine improves cognitive dysfunction during hypertension.
      The aim of the present study was to determine whether a combination of
      atorvastatin and amlodipine causes sympathoinhibition via reduction of oxidative
      stress in the RVLM and improves cognitive dysfunction of hypertensive rats.
      METHODS AND RESULTS: Stroke-prone spontaneously hypertensive rats (SHRSPs), as a
      hypertensive model with sympathoexcitation, were divided into 4 groups; a
      combination of atorvastatin and amlodipine-treated (COM), atorvastatin-treated
      (ATR), amlodipine-treated (AML), hydralazine-treated (HYD), and vehicle-treated
      SHRSPs (VEH). After treatment for 28 days, the mean blood pressure did not change
      in ATR rats, and was reduced to the similar levels in COM, AML, and HYD rats.
      However, SNS activation and oxidative stress in the RVLM were significantly lower
      only in COM than in ATR, AML, HYD, and VEH rats. Cognitive performance and
      manganese-superoxide dismutase activity in the hippocampus were significantly
      higher, and oxidative stress in the hippocampus was significantly lower in COM
      than in VEH, AML, and HYD rats to a greater extent than in ATR rats. CONCLUSIONS:
      A combination of atorvastatin and amlodipine causes sympathoinhibition via an
      anti-oxidant in the RVLM and improves cognitive dysfunction via an anti-oxidant
      in the hippocampus in hypertensive rats, independent of the blood pressure
      lowering effect.

PMID- 22664572
TI  - Ophthalmic artery Doppler waveform in the newborn.
AB  - BACKGROUND: The ophthalmic artery Doppler waveform (OADW) is thought to correlate
      with severity of systemic atherosclerosis. The goal of the present study was to
      evaluate risk of cardiovascular disease (CVD) in newborns small for gestational
      age (SGA) and appropriate for gestational age (AGA). METHODS AND RESULTS: A total
      of 15 SGA and 26 AGA newborns were enrolled in the study. OADW was compared
      between SGA and AGA groups. The median Doppler maximums of both eyes in the SGA
      group were significantly smaller than in the AGA group (maximum average velocity
      (max A) 6.4cm/s vs. 8.3cm/s, P=0.028; maximum end diastolic velocity (max D)
      2.2cm/s vs. 3.4cm/s, P=0.003). The maximums of both eyes for the maximum
      resistivity index (max RI) and maximum pulsatility index (max PI) in the SGA
      group were significantly greater than in the AGA group (RI, 0.88 vs. 0.82,
      P=0.005; PI, 2.23 vs. 1.72, P=0.002). When a multiple linear regression analysis
      of the SGA group with a stepwise procedure was applied to positive variables from
      2-sided comparisons, significant correlations were noted for max A and max PI
      (max A: R(2)=0.495, beta=0.541, P=0.034; max PI: beta=-3.318, P=0.012).
      CONCLUSIONS: OADW in SGA newborns may be related to future risk of CVD, which is
      undetectable in infancy, and can provide information to estimate future
      cardiovascular health.

PMID- 22664573
TI  - Sirolimus eluting coronary stent implantation in patients on maintenance
      hemodialysis: the OUCH study (outcome of cypher stent inhemodialysis patients).
AB  - BACKGROUND: Pivotal studies on drug-eluting stents have excluded hemodialysis
      (HD) patients. No quantitative coronary angiography (QCA) analysis has been
      reported. METHODS AND RESULTS: The OUtcome of Cypher stent in Hemodialysis
      patients (OUCH) Study is a prospective non-randomized single-arm registry
      designed to assess the results of sirolimus-eluting stents in HD patients, with
      follow-up QCA in an independent core laboratory. The primary endpoint was the
      occurrence of target-vessel failure (TVF) defined as cardiac death, myocardial
      infarction (MI), and target-vessel revascularization (TVR) at 1 year. A total of
      117 patients were enrolled. The TVF rate was 24.9% (2.6% cardiac death, 1.4% MI,
      23.9% TVR), and stent thrombosis was documented in 1 patient (0.9%). Coronary
      calcification was a predictor of TVF. Late lumen loss (LLL) averaged 0.69+/
      0.93mm. The histogram of LLL showed that a total of 76% of lesions were
      distributed the same normally as that in normal renal function (average LLL
      0.20+/-0.29mm), but 24% of lesions were outliers (average LLL 2.07+/-0.62mm).
      CONCLUSIONS: This report describes different clinical and QCA results in HD
      patients as higher TVF rate, different predictive factors, and different
      histogram of LLL compared with normal renal function. The different histogram of
      LLL was the existence of many outliers with the same average and the same
      deviation, suggesting the loss of sirolimus had an effect on a significant number
      of HD patients.

PMID- 22664574
TI  - Pleiotropy of segregating genetic variants that affect honey bee worker life
      expectancy.
AB  - In contrast to many other complex traits, the natural genetic architecture of
      life expectancy has not been intensely studied, particularly in non-model
      organisms, such as the honey bee (Apis mellifera L.). Multiple factors that
      determine honey bee worker lifespan have been identified and genetic analyses
      have been performed on some of those traits. Several of the traits are included
      in a suite of correlated traits that form the pollen hoarding syndrome, which was
      named after the behavior to store surplus pollen in the nest and is tied to
      social evolution. Here, seven quantitative trait loci that had previously been
      identified for their effects on different aspects of the pollen hoarding syndrome
      were studied for their genetic influence on the survival of adult honey bee
      workers. To gain a more comprehensive understanding of the genetic architecture
      of worker longevity, a panel of 280 additional SNP markers distributed across the
      genome was also tested. Allelic distributions were compared between young and old
      bees in two backcross populations of the bi-directionally selected high- and low
      pollen hoarding strain. Our results suggest a pleiotropic effect of at least one
      of the behavioral quantitative trait loci on worker longevity and one significant
      and several other putative genetic effects in other genomic regions. At least one
      locus showed evidence for strong antagonistic pleiotropy and several others
      suggested genetic factors that influence pre-emergence survival of worker honey
      bees. Thus, the predicted association between worker lifespan and the pollen
      hoarding syndrome was supported at the genetic level and the magnitude of the
      identified effects also strengthened the view that naturally segregating genetic
      variation can have major effects on age-specific survival probability in the
      wild.

PMID- 22664575
TI  - Age, growth and size interact with stress to determine life span and mortality.
AB  - Individuals in a large experimental field population, of the short-lived
      perennial species Plantago lanceolata, were followed to determine the sources of
      variation that influence mortality and life span. The design included multiple
      age groups with initially similar genetic structure, which made it possible to
      separate age effects from period effects and to identify the genetic component to
      variation in life span. During a period of stress, individuals of all ages showed
      parallel increases in mortality but different cohorts experienced this period of
      high mortality at different ages. This then influenced the distribution of life
      spans across cohorts. Age and size-age interactions influenced mortality during
      the period of stress. Smaller individuals died but only if they were old.
      Additionally, growth and age interacted with stress such that older individuals
      had negative growth and high mortality whereas younger individuals had positive
      growth and relatively lower mortality during stress. The results of this study
      show that it is not simply the environment that can have a major impact on
      demography in natural populations; rather, age, size and growth can interact with
      the environment to influence mortality and life span when the environment is
      stressful.

PMID- 22664576
TI  - Trading stages: life expectancies in structured populations.
AB  - Interest in stage-and age structured models has recently increased because they
      can describe quantitative traits such as size that are left out of age-only
      demography. Available methods for the analysis of effects of vital rates on
      lifespan in stage-structured models have not been widely applied because they are
      hard to use and interpret, and tools for age and stage structured populations are
      missing. We present easily interpretable expressions for the sensitivities and
      elasticities of life expectancy to vital rates in age-stage models, and
      illustrate their application with two biological examples. Much of our approach
      relies on trading of time and mortality risk in one stage for time and risk in
      others. Our approach contributes to the new framework of the study of age- and
      stage-structured biodemography.

PMID- 22664577
TI  - Plasma oxidative stress parameters in men and women with early stage Alzheimer
      type dementia.
AB  - It is well known that oxidative stress is one of the earliest events in
      Alzheimer's disease pathogenesis, indicating that may play a key role in this
      disease. In our study, we measured the levels of oxidative stress indicators
      (TBARS and protein carbonyls content) and the non-enzymatic (glutathione (GSH)
      and oxidized glutathione (GSSG)) and enzymatic (glutathione peroxidase (GPx),
      catalase (CAT) and superoxide dismutase (SOD)) defense systems in the plasma of
      46 patients diagnosed of ATD and 46 age-matched controls. We found decreased
      levels in total GSH in ATD patients, although healthy control women showed lower
      levels of total GSH than healthy control men. On the contrary, we found increased
      levels of TBARS and carbonyl groups content in ATD patients in both genders. The
      activity of the plasma antioxidant enzymes showed no changes for SOD activity in
      ATD patients, independently of the gender, although western blot analysis showed
      an increase in SOD-1 protein. CAT activity was also decreased in ATD patients,
      although this decrease is mainly due to the decrease found in men but not in
      women. However, western blot analysis did not show differences in CAT protein
      between controls and ATD patients. Finally, a decrease of GPx activity was found
      in ATD patients in both genders. However, as with CAT protein, western blot
      analysis did not show differences in GPx protein between controls and ATD
      patients. Our results suggest that there is a defect in the antioxidant defense
      system that is incapable of responding to increased free radical production,
      which may lead to oxidative damage and the development of the pathological
      alterations that characterize the neurodegenerative disorder of patients with
      ATD. Thus, oxidative damage could be one important aspect for the onset of ATD
      and oxidative stress markers could be useful to diagnose the illness in their
      earliest stages through both non-invasive, reliable and cost-affordable methods.

PMID- 22664578
TI  - Blood pressure, smoking and alcohol use, association with vascular dementia.
AB  - The success of the ageing global population brings with it a growth in the number
      of dementia sufferers. Older adults are at highest risk of dementia and are
      likely to manifest both vascular and Alzheimer's pathology. Blood pressure also
      changes with ageing and there is evidence linking high blood pressure in midlife
      to an increased risk of later dementia. Data from later life is sparser. A number
      of intervention trials have been carried out with antihypertensives and have
      shown mixed results with regard to cognitive and dementia outcomes (both dementia
      overall and of vascular and Alzheimer's types). Meta-analyses have in general not
      found an association between blood pressure lowering and reduced dementia
      incidence, although the number of cases reported in the placebo controlled trials
      is invariably lower in the actively treated group. Systematic reviews and meta
      analyses have also been published with regard to smoking and alcohol use and
      incident dementia. Despite mixed reports, overall smoking was associated with an
      increased risk of later dementia and alcohol with a 'U' or 'J' shaped
      relationship. Following the systematic reviews subsequent publications tend to
      report similar findings. The literature in this area suffers from differing
      populations, lengths of follow up and assessments of both risk factor and
      outcome. However, at present, maintenance of cognitive function would seem to be
      best served by treating cardiovascular risk factors in accordance with current
      guidelines, controlling blood pressure, reducing smoking and if consuming alcohol
      doing so in moderation. This review will concentrate on the prevention of
      dementia and attempt to provide an overview of the evidence relating to vascular
      related dementia and the potential risk factors of hypertension, alcohol use and
      smoking behaviour.

PMID- 22664579
TI  - A pilot trial to predict frailty syndrome: the Japanese Health Research Volunteer
      Study.
AB  - Most definitions of frailty utilize US populations in their development. The
      concept of frailty has not been well studied in Japan, which has the largest
      percentage of older patients (per capita) in the world. We created a 5-year
      prospective cohort study of community-dwelling older Japanese adults.
      Participants were not frail at baseline, based on our definition adapted from the
      Canadian Study for Health and Aging Clinical Frailty Scale. Participants
      underwent a comprehensive geriatric assessment (CGA) at baseline, and final
      assessments were either in person or via mailed survey. We enrolled 407
      individuals (184 men, mean age 78 +/- 4 years; 223 women, mean age 77 +/- 4
      years). Sixty-five participants met criteria for frailty by the end of the study.
      In univariate analyses, eighteen separate parameters were associated with
      frailty, some of which included: age, gender, handgrip, timed walk, systolic
      blood pressure, pulse pressure, cognitive status, living alone, and hearing
      deficits. In multivariate analyses, the following elements remained associated
      with frailty: timed walk, pulse pressure, cognition deficits and hearing
      deficits. We established cut-off points for timed walk (5m/3s) and pulse pressure
      (60 mmHg). We then created a simple additive score for these four factors
      (present = 1; absent = 0). A score of 0 had a 93% negative predictive value for
      frailty while a score of 4 had a 70% positive predictive value. While further
      study is needed, this work creates an easy-to-administer tool that may be
      generalizable to other populations.

PMID- 22664580
TI  - The effects of pronator quadratus repair on outcomes after volar plating of
      distal radius fractures.
AB  - OBJECTIVES: The purpose of this study was to evaluate forearm rotation after
      volar plating of the distal radius fractures with and without pronator quadratus
      repair. DESIGN: This was an institutional review board-approved retrospective
      review of prospectively collected data. SETTING: The study was conducted at an
      Academic Medical Center. PATIENTS: Over a 5-year period, 606 patients with distal
      radius fractures (OTA classifications 23-A through 23-C) were enrolled in an
      institutional review board-approved, prospectively collected, distal radius
      database. One hundred and seventy-five patients underwent open reduction and
      internal fixation with volar plating. Of these, 112 patients had complete 1-year
      follow-up (6 weeks, 3, 6, and 12 months) and were included in this study.
      INTERVENTION: Volar plating of the distal radius was performed with pronator
      quadratus repair (group A), versus volar plating without pronator quadratus
      repair (group B). Surgeries in group A were performed by a fellowship trained
      hand surgeon utilizing volar plates from Depuy Orthopedics (Warsaw, IN), whereas
      the surgeries in group B were performed by a fellowship trained orthopedic trauma
      surgeon utilizing volar plates from Stryker (Mahwah, NJ). MAIN OUTCOME
      MEASUREMENTS: Primary outcomes include forearm range of motion. Secondary
      outcomes include grip strength, pain levels, functional outcomes (DASH scores),
      radiographs, and complications. RESULTS: Baseline and demographic characteristics
      of the patients were similar between the 2 groups. There was no difference in
      mean pronation (P = 0.08) at 1 year. Among secondary analyses, radial deviation
      was significantly different (P = 0.03); however, pain (P = 0.13) and DASH scores
      (P = 0.14) were not. The only patient that requested plate removal had the
      pronator repaired (group A). CONCLUSIONS: We conclude that there is no advantage
      in repairing the pronator quadratus during volar plating of distal radius
      fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 22664581
TI  - Detailed analysis of an idic(Y)(q11.21) in a mosaic karyotype.
AB  - Abnormalities involving sex chromosomes account for approximately 0.5% of live
      births. The phenotypes of individuals with mosaic cell lines that exhibit
      structural aberrations of the X and Y chromosomes are variable and difficult to
      predict. Phenotypes associated with sex chromosome mosaicism vary from females
      with Turner syndrome to males with infertility, and include individuals with
      ambiguous genitalia. In this study, we report a 17-year-old male with phenotypic
      features of Klinefelter syndrome with an isodicentric Y chromosome and a final
      karyotype of 45,X[4]/46,X,idic(Y)(q11.21)[95]/47,XX,+idic(Y)(q11.21)[1].
      Application of high resolution molecular cytogenetic techniques as well as
      molecular studies revealed two copies of the sex-determining region of Y
      chromosome (SRY) gene and two centromers. Additionally, the breakpoint in Yq11.21
      was narrowed down between positions 13.4 and 14.3 MB (hg18). We present a patient
      with partial disomy of Ypter to Yq11.21 in the majority of the patient cells,
      showing phenotypic features of Klinefelter syndrome. The syndrome may have
      occurred due to a more prominent presence of the cell line 47,XX,+idic(Y)(q11.21)
      detected only once in 1% of the peripheral blood cells. This finding may prove
      helpful in similar cases with symptoms of Klinefelter syndrome, but which exhibit
      an absence of the cell line 47,XXY in peripheral blood.

PMID- 22664582
TI  - Chemical inhibition of potato ABA-8'-hydroxylase activity alters in vitro and in
      vivo ABA metabolism and endogenous ABA levels but does not affect potato
      microtuber dormancy duration.
AB  - The effects of azole-type P450 inhibitors and two metabolism-resistant abscisic
      acid (ABA) analogues on in vitro ABA-8'-hydroxylase activity, in planta ABA
      metabolism, endogenous ABA content, and tuber meristem dormancy duration were
      examined in potato (Solanum tuberosum L. cv. Russet Burbank). When functionally
      expressed in yeast, three potato CYP707A genes were demonstrated to encode
      enzymatically active ABA-8'-hydroxylases with micromolar affinities for (+)-ABA.
      The in vitro activity of the three enzymes was inhibited by the P450 azole-type
      inhibitors ancymidol, paclobutrazol, diniconazole, and tetcyclasis, and by the 8'
      acetylene- and 8'-methylene-ABA analogues, with diniconazole and tetcyclasis
      being the most potent inhibitors. The in planta metabolism of [(3)H](+/-)-ABA to
      phaseic acid and dihydrophaseic acid in tuber meristems was inhibited by
      diniconazole, tetcyclasis, and to a lesser extent by 8'-acetylene- and 8'
      methylene-ABA. Continuous exposure of in vitro generated microtubers to
      diniconazole resulted in a 2-fold increase in endogenous ABA content and a
      decline in dihydrophaseic acid content after 9 weeks of development. Similar
      treatment with 8'-acetylene-ABA had no effects on the endogenous contents of ABA
      or phaseic acid but reduced the content of dihydrophaseic acid. Tuber meristem
      dormancy progression was determined ex vitro in control, diniconazole-, and 8'
      acetylene-ABA-treated microtubers following harvest. Continuous exposure to
      diniconazole during microtuber development had no effects on subsequent sprouting
      at any time point. Continuous exposure to 8'-acetylene-ABA significantly
      increased the rate of microtuber sprouting. The results indicate that, although a
      decrease in ABA content is a hallmark of tuber dormancy progression, the decline
      in ABA levels is not a prerequisite for dormancy exit and the onset of tuber
      sprouting.

PMID- 22664583
TI  - Foliar pathogenesis and plant water relations: a review.
AB  - As the world population grows, there is a pressing need to improve productivity
      from water use in irrigated and rain-fed agriculture. Foliar diseases have been
      reported to decrease crop water-use efficiency (WUE) substantially, yet the
      effects of plant pathogens are seldom considered when methods to improve WUE are
      debated. We review the effects of foliar pathogens on plant water relations and
      the consequences for WUE. The effects reported vary between host and pathogen
      species and between host genotypes. Some general patterns emerge however. Higher
      fungi and oomycetes cause physical disruption to the cuticle and stomata, and
      also cause impairment of stomatal closing in the dark. Higher fungi and viruses
      are associated with impairment of stomatal opening in the light. A number of
      toxins produced by bacteria and higher fungi have been identified that impair
      stomatal function. Deleterious effects are not limited to compatible plant
      pathogen interactions. Resistant and non-host interactions have been shown to
      result in stomatal impairment in light and dark conditions. Mitigation of these
      effects through selection of favourable resistance responses could be an
      important breeding target in the future. The challenges for researchers are to
      understand how the effects reported from work under controlled conditions
      translate to crops in the field, and to elucidate underlying mechanisms.

PMID- 22664584
TI  - Predictors of high on-treatment platelet reactivity early after clopidogrel
      loading in ST-elevation myocardial infarction.
AB  - BACKGROUND: Given that platelet inhibition is crucial when ST-elevation
      myocardial infarction (STEMI) patients undergo primary PCI (PPCI), the
      identification of factors associated with early high on-treatment platelet
      reactivity may be important. METHODS AND RESULTS: Consecutive STEMI patients
      admitted for PPCI were considered for platelet reactivity assessment 2 h after
      loading with 600 mg clopidogrel using the VerifyNow point-of-care P2Y12 assay. A
      cut-off of >=235 P2Y12 reaction units indicated high on-treatment platelet
      reactivity. Out of 92 STEMI patients, 63 (68.5%) were found to have high on
      treatment platelet reactivity. Patients with high on-treatment platelet
      reactivity had received upstream clopidogrel loading and pantoprazol more
      frequently, had lower admission hemoglobin and tended to have an impaired renal
      function compared to those with an adequate response to clopidogrel. On
      multivariate analysis, upstream clopidogrel loading and creatinine clearance <60
      ml/min were independently associated with higher risk for high on-treatment
      platelet reactivity (relative risk [RR]=1.55, 95% confidence interval [CI]: 1.11
      2.17, P=0.01; RR=1.31, 95% CI: 1.008-1.71, P=0.04, respectively). CONCLUSIONS: In
      patients with STEMI undergoing PPCI, use of upstream clopidogrel and impaired
      renal function independently predict high on-treatment platelet reactivity
      assessed as early as 2h following 600 mg of clopidogrel loading dose on point-of
      care P2Y12 function assay. 

PMID- 22664585
TI  - Adipose tissue: an alternative source for therapeutic angiogenesis.

PMID- 22664586
TI  - Combination of beta-blocker and milrinone for acute heart failure.

PMID- 22664587
TI  - Therapy: Antibiotics or appendectomy for uncomplicated acute appendicitis?

PMID- 22664589
TI  - Infection: High-throughput drug screen strikes gold in the search for a new
      amoebiasis treatment.

PMID- 22664588
TI  - Familial pancreatic cancer--current knowledge.
AB  - Familial pancreatic cancer (FPC) describes families with at least two first
      degree relatives with confirmed exocrine pancreatic cancer that do not fulfil the
      criteria of other inherited tumour syndromes with increased risks of pancreatic
      cancer, such as Peutz-Jeghers syndrome, hereditary pancreatitis, and hereditary
      breast and ovarian cancer. The inheritance of FPC is mostly autosomal dominant
      and with a heterogeneous phenotype. The major gene defect is yet to be
      identified, although germline mutations in BRCA2, PALB2 and ATM are causative in
      some FPC families. Expert consensus conferences considered it appropriate to
      screen for pancreatic cancer in high-risk individuals using a multidisciplinary
      approach under research protocol conditions. However, neither biomarkers nor
      reliable imaging modalities for the detection of high-grade precursor lesions are
      yet available. Most screening programmes are currently based on findings from
      endoscopic ultrasonography and MRI, and data has demonstrated that precursor
      lesions of pancreatic cancer can be identified. No consensus exists regarding the
      age to initiate or stop screening and the optimal intervals for follow-up. Timing
      and extent of surgery as a treatment for FPC are debated. This Review focuses on
      the clinical phenotype of FPC, its histopathological characteristics, known
      underlying genetic changes and associated genetic counselling and screening.

PMID- 22664590
TI  - Liver transplantation: Boceprevir increases levels of ciclosporin and tacrolimus.

PMID- 22664592
TI  - Translocation of HSP27 into liver cancer cell nucleus may be associated with
      phosphorylation and O-GlcNAc glycosylation.
AB  - It has been reported that the dynamic interplay between O-GlcNAcylation and O
      phosphorylation is responsible for altering the activity or localization of heat
      shock proteins. The aim of this study was to determine whether dynamic interplay
      between O-GlcNAcylation and O-phosphorylation of HSP27 in hepatocellular cancer
      (HCC) cells affect its entry into the nucleus. We demonstrate that the entry of
      HSP27 into the nucleus correlated with its phosphorylation through transfecting
      HCC cells with plasmids coding for wild-type HSP27 (HSP27-WT), its non
      phosphorylatable (HSP27-3A) and pseudophosphorylated (HSP27-3D) mutants, however,
      not all of the endogenous or exogenous nuclear HSP27 was modified by
      phosphorylation. We observed that HSP27 was modified with O-GlcNAc glycosylation
      in HCC cells and report that at conserved Ser residues of HSP27, alternative
      phosphorylation and O-GlcNAc modification can be predicted by the YinOYang 1.2
      method. Furthermore, after P79350 or combined SB203580 and PUGNAc treatment,
      increased nuclear import of HSP27-WT and HSP27-3D implied that the entry of HSP27
      into the nucleus was not only correlated with phosphorylation, but also with O
      GlcNAc glycosylation. Collectively, O-GlcNAcylation of HSP27 in HCC cells may be
      a novel regulatory mode of HSP27 function, particularly for its entry into the
      nucleus. Crosstalk or interplay between glycosylation and phosphorylation of
      HSP27 could regulate its subcellular localization and biological functions in
      liver cancer.

PMID- 22664593
TI  - [Theory of significant learning: development and evaluation of virtual classroom
      in Moodle platform].
AB  - This study aimed to develop and evaluate the virtual classroom on the Theory of
      Meaningful learning for undergraduates in nursing. It is applied research,
      production technology, developed in five phases: design and planning, content
      development and instructional designer, creation of educational materials,
      learning portal deployment in Moodle (Modular Object-Oriented Dynamic Learning
      Environment) and evaluation by judges. The class was developed and was approved,
      after evaluation by the judges, and adjustments, and will integrate the
      discipline Methodology of Nursing Teaching I, Degree Course Nursing School of
      USP. We believe that the purpose of this study favors the formation of the
      licensing and therefore the future of teaching nursing in a critical and
      reflective, with the components of a profile of the prospect of seeking and using
      new knowledge for the development of their professional practice.

PMID- 22664591
TI  - Endoscopic submucosal dissection--current success and future directions.
AB  - More than 10 years have passed since endoscopic submucosal dissection (ESD) was
      first developed in Japan. ESD enables en bloc complete resection of superficial
      gastrointestinal neoplasms regardless of the size and location of the lesions.
      With improvements in techniques and devices, excellent therapeutic results have
      been achieved despite the inherent technical difficulties of this procedure. ESD
      aiming for curative treatment can be performed for gastrointestinal neoplasms
      without risk of lymph node metastasis. Accurate histopathologic examination of
      the resected specimen is required to determine the risk of lymph node metastasis,
      for which en bloc resection is beneficial. Owing to the high success rate of en
      bloc complete resection and accurate histopathologic examination, tumour
      recurrence rates after ESD are reported to be very low in Japan. Excellent
      results of ESD in a large number of cases have also been reported from other
      Asian countries such as South Korea, Taiwan and China. Although scepticism exists
      among Western clinicians regarding the application of ESD, it is developing
      slowly and reports indicate promising results in some European countries. With
      further development of technologies, such as endoscopic robotics, ESD could
      become the worldwide treatment of choice for early gastrointestinal neoplasms.

PMID- 22664594
TI  - Join Action Group in the first year of National Network of ABEn.

PMID- 22664595
TI  - [Management practices of peripherally inserted central catheter at a neonatal
      unit].
AB  - The study aimed to describe the management of Peripherally Inserted Central
      Catheters insertion in neonates admitted at a neonatal intensive care unit of a
      private hospital, after implementation of the institutional protocol. An
      exploratory, quantitative descriptive study with prospective data collection was
      carried out. Data of 45 catheters insertion were analyzed. The rate of catheter's
      with elective removal was 63.8%, and catheter's complications rate was 30.8%. The
      most frequently complications were rupture (15.4%), occlusion (11%) and
      accidental dislodgement (4.4%). No records about the catheter dressings were
      observed in 33% of catheter's insertion. One conclude that the complications were
      related to care practices of the catheter, requiring professional training and
      new tools to record the care provided in relation to the catheter's management.

PMID- 22664596
TI  - [Care with the child's health and validation of an educational technology for
      riverside families].
AB  - This study aimed to assess the knowledge and ways of caring for the child health
      0-5 years between riverine (Phase 1), and to validate an educational technology
      (Phase 2). It was carried out a descriptive qualitative study. With the mothers,
      focus groups and content analysis were used, and with judges-specialists and
      target-public-applied, forms. The study revealed that the concern with the care
      of a child between the riverine families permeates the adversity daily, with
      dedication and commitment of these families in maintaining the health of their
      children. The sensitivity listening of mothers indicated the need for a closer
      relationship between nursing professionals and family. The validation of the
      educational technology was convergent, within the parameters considered adequate.

PMID- 22664597
TI  - [Voluntary abortion and domestic violence among women attended at a public
      maternity hospital of Salvador-BA].
AB  - Quantitative study in order to study domestic violence in women with induced
      abortion. Interviews were conducted with 147 women hospitalized for induced
      abortion in a public maternity hospital in Salvador, Bahia. The subjects are
      characterized by mostly women, black, poorly educated, economically dependent on
      spouses, experienced psychological abuse, physical and sexual abuse committed by
      their spouses. Almost half of the women were victims of domestic violence during
      the current pregnancy, and that was the reason for inducing abortion for 67% of
      them. The study reveals an association between experience of domestic violence
      and induced abortion. As mental health consequences, they developed symptoms of
      post trauma stress disorder. It is necessary that the health professionals
      consider the cues to identify domestic violence as a health problem associated
      with induced abortion, which requires a transformation on the training model,
      including domestic violence as a health issue.

PMID- 22664598
TI  - [Breast cancer: risk factors and early detection].
AB  - The objective was to identify risk factors, according to INCA, for breast cancer,
      analyzing knowledge and BSE practice, mammography and ECM, and verify the
      relationship between age and education with knowledge and conducting such
      examinations. Data were collected during ten months, through interviews with
      women in chemotherapy against breast cancer, and analyzed by simple statistics.
      There was agreement with the minority of risk factors. All examinations were
      known and practiced by most, except mammography performed in half. The older ones
      mainly practiced BSE and mammography, and the younger ECM. There was a directly
      proportional relationship between knowledge and education of these exams. Health
      professionals need to guide the public about breast cancer, to allow more
      resolute and less mutilating treatments.

PMID- 22664599
TI  - [Experiences to cope with HIV among infected women].
AB  - The study aimed to describe HIV-positive women's reports and experiences in
      coping with the infection. A qualitative study was carried out in the context of
      a specialized care service in Fortaleza-CE in 2007. Participants were 14 women
      diagnosed with HIV infection, who participated in tape recorded interviews. The
      analysis of interviews contents revealed the category Motivations for coping with
      HIV/AIDS and the subcategories religiosity, social and family support, presence
      of children and professional complicity as positive factors for coping with the
      infection. In conclusion, these women need professional and family care and
      support to remain stimulated in the care process.

PMID- 22664600
TI  - [Barriers and facilitators aspects of adherence to antiretroviral therapy in Belo
      Horizonte-MG].
AB  - The aim of this study was to know the constraining and facilitating aspects of
      adherence to highly active antiretroviral therapy (HAART) among people with
      HIV/AIDS. This was a qualitative study, carried out with 26 individuals receiving
      HAART and assisted by a referral service in Belo Horizonte, Minas Gerais, Brazil.
      The analysis of the interviews regarding the constraints found by users, resulted
      in categories relating to Day-by-day life, HIV representations, and the
      complexity of the treatment. As for the facilitating aspects, the categories
      found were absence of side effects, remembering the symptoms of the disease,
      improved survival, and influences from the social networks. Results have shown
      the importance of an effective follow-up so that health care professionals can
      build strategies to improve adherence to HAART together with the individuals.

PMID- 22664601
TI  - [Barriers to hypertension treatment].
AB  - The objective was to describe the barriers faced by people with hypertension for
      non compliance to treatment and control the levels of blood pressure. This is a
      transversal and descriptive study which was carried out in 6 basic health units
      in Fortaleza-Ceara, Brazil. The population consisted of 246 people enrolled in
      the program to Control Hypertension for at least a year. Data were collected
      using a structured interview and electronic chart. Of them, 69 showed normal
      blood pressure levels. The main barriers discovered were: poor financial
      condition, continuous treatment with many medicines and practice physical
      activity. It was concluded that barriers to the anti-hypertensive treatment
      include the sick people, their environment and their access to health care.

PMID- 22664602
TI  - [Self-image of clients with colostomy related to the collecting bag].
AB  - The study aimed to analyze the perception of patients with colostomy in the use
      of the collection bag. It was conducted a descriptive qualitative approach, on
      the Center for Integrated Health Lineu Araujo, Teresina-PI, Brazil. Ten clients
      with colostomy bag participated in the survey. Data were generated through semi
      structured interviews. Content analysis has revealed the feelings, the changes
      and how the process of adaptation of the person with the colostomy bag occurs. It
      was found that the relationship between the collection bag and the person with a
      colostomy is filled with negative feelings, significant changes in physical,
      psychological and sexual order, and in the web of his/her social relationships.

PMID- 22664603
TI  - [Activity of motorcycle taxi driver: risks and weaknesses self referred].
AB  - Descriptive research, with qualitative approach, that aimed to identify
      occupational hazards and weaknesses self-reported by motorcycle drivers. Data
      were collected in the first half of 2010 through interviews with twelve
      motorcycle drivers, invited to participate and work on two central points of a
      municipality in the state of Rio Grande do Sul, Brazil. Data were analyzed using
      thematic analysis, from which emerged five categories. According to subjects'
      perception, accidents and assaults represent the greatest risks of the
      profession. It can be inferred that the actions of health education and disease
      prevention should be governmental and no governmental strategies that would
      assign value to the health and safety of these workers.

PMID- 22664604
TI  - [Protocol of nursing care to traumatized patients in the aerospace environment:
      care before flight].
AB  - The study aimed to present a protocol for nursing care in pre aerospace removing
      of adult victims of trauma. A qualitative convergent care research was performed
      at the Division of Air Operations in the municipality of San Jose-SC, Brazil,
      from April to June 2010. The study was based on the principles of the Pre
      hospital Trauma Life Support. Individual interviews and group meetings were used.
      Eight nurses participated in the service. The proposed protocol includes safety
      boarding, disembarking, assessment of the scene, primary assessment, secondary
      assessment and stabilization of the patient. The protocol will provide a safer
      nursing practice care to patients aero removed.

PMID- 22664605
TI  - [The nurse interacting and relating: the context of nursing care in a semi
      intensive unit].
AB  - This study aimed to understand the meaning of nursing care to nurses in the
      hospital. This is a qualitative research, based on theoretical and methodological
      assumptions of symbolic interaction. It was performed in a semi-intensive unit of
      a tertiary public hospital in Fortaleza-CE, Brazil. Eleven nurses participated on
      it. For data collection, it was used semi-structured interviews and field
      observation simple and, in data processing it was performed thematic category.
      The ethical aspects have been respected. It was observed that the nursing care
      means the establishment of the nurse's interpersonal relationships with other
      health professionals, patients and their accompanying persons. It was understood
      that, for nurses of the hospital, nursing care means social interaction with
      people.

PMID- 22664606
TI  - [Experiences and feelings of nursing professionals in caring of the dead
      patient].
AB  - This study aimed to understand the experiences and feelings of ten professional
      nurses related to the dead patient, in a private hospital of the metropolitan
      area of Porto Alegre-RS, Brazil. We used a qualitative approach, descriptive,
      exploratory, with data collected in July 2009, through interviews with semi
      structured questionnaire. The results were grouped into the categories: feelings
      about the patient's death, reactions to the death and preparing the patient's
      body. It was concluded that the most remarkable experiences were related to the
      first contact with the death, the presence of emotional bonding with patients and
      families and the patients' age at death. The latter two are considered hindering
      elements of care offered to patients without life.

PMID- 22664607
TI  - [Characterization of the assistance of a hematology unit].
AB  - This study aimed to describe the characteristics of service in a Hemotherapy Unit
      in the interior of the state of Sao Paulo in 2009. All ethical guidelines were
      followed and a survey was carried out in the database of the Unit. During the
      observed period, the Unit shows greater rate of repetition donors, with low
      levels of adverse reactions and 100% of donors' satisfaction. The units of
      clinical medicine and intensive therapy were the sectors with highest consumption
      of transfusions at the hospital service. The described unit is self-sufficient at
      managing its resources. The present study shows the need to explore the
      dimensions of the professional roles in hemotherapy, the possibilities of finding
      new donors, the reasons that lead patients to donate blood, characteristics,
      epidemiological profile and satisfaction of receptors.

PMID- 22664608
TI  - [Work process of nurses' aides and nursing technicians in primary health care].
AB  - This research had as its object the practice of nurses' aides and nursing
      technicians in service of Primary Health Care of the city of Ribeirao Preto-SP,
      Brazil. The aims were: characterize the work process of these agents, analyze his
      concepts on the constituent elements of working process and identify and analyze
      the difficulties and facilities in developing the work process from the
      perspective of integrality. It was descriptive and qualitative. To collect the
      data were used participant observation and the semi-structured interview and the
      data were dealt with thematic analysis. It was found the predominance of the
      organization of the work process to assist people with the need to deal with
      diseases/health problems and met potential for development of the work process
      for integrality health care. It is suggested the practice of permanent education,
      the qualification to listening and new training policies for these workers.

PMID- 22664609
TI  - [Meaning of healthy living for health users, professionals and managers].
AB  - Qualitative research guided by grounded theory method that aimed to understand
      the meaning of healthy living in a community socially vulnerable for health
      users, professionals and managers. Data were collected through individual
      interview with 25 participants, among health users, professionals and managers.
      Data analysis was done in a comparative way according to grounded theory. For
      health users, healthy living is associated with basic living conditions, with
      inclusion opportunities and social participation and with interaction and
      associative possibilities; for health professionals, healthy living is related to
      political and social articulations; and for managers, it is related to the
      development of strategies that can reorient the current health model. We conclude
      that healthy living is a singular, plural and complex process that is built based
      on the imaginary and on the experiences of each human being.

PMID- 22664610
TI  - [Cross-mapping of terms of the axes time, location, means and client between
      different versions of ICNP(r) and CIPESC(r)].
AB  - The ICNP(r) model of seven axes resulted in the transfer of terms between the
      axes, conceptual modifications, inclusion and exclusion of terms. This
      descriptive, bibliographic study, mapped out the terms of the axes "Time",
      "Location", "Means" and "Client" among Beta-2, 1.0 and 1.1 versions of the
      ICNP(r) and CIPESC(r). The mapping located the terms of these axes in the
      different versions of the ICNP(r) and CIPESC(r). It was performed to classify the
      semantic equivalence of terms and concepts. The result shows that some changes
      have the objective of reducing ambiguities and redundancies; others do not allow
      the verification of the criterion for exclusion, inclusion and migration of
      terms. It is imperative to establish concepts of consensus by the group
      responsible for building the terminology in order to minimize the misuse or
      improper use of terms. It is necessary to revise the list of actions in the
      vocabulary inventory of CIPESC(r).

PMID- 22664611
TI  - [Human and Social Sciences in the training of the first nurses 'cariocas' and
      'paulistanas'].
AB  - This historical and documental study aimed to describe and analyze the place that
      the Human and Social Sciences occupied in the first curriculum of the Anna Nery
      Nursing School (EEAN) and of the Sao Paulo Hospital Nursing School (EEHSP),
      identifying the similarities and differences between them. As a methodology, the
      curricula of these schools were analyzed by comparing them and seeking, between
      primary and secondary sources, information of the contribution of Human and
      Social Sciences in the training of pioneer nurses in modern nursing in Brazil. It
      was concluded that the humanities subjects occupied a secondary place in the
      studied curricula in comparison with the technical disciplines and the
      utilitarian aspect required by this profession at that time.

PMID- 22664612
TI  - [Death and dying process: evidences from the literature of nursing].
AB  - The objective was to identify the profile of production and analyze perceptions,
      feelings and confrontations on the process of death and dying in the practice
      evidenced in nursing scientific production in the period 1994 to 2009. There was
      a qualitative, descriptive research, developed through a systematic literature
      review with metasynthesis from the meta-ethnographic method. Ten studies met the
      inclusion criteria, this set was subjected to quality assessment checklist with
      Critical Appraisal Skills Programme. Subjects perceive this process as a
      transition, separation and finitude. This is permeated with feelings of
      frustration and powerlessness and the most effective interventions to this issue
      is the development of coping strategies that vary with the reality of each
      individual.

PMID- 22664613
TI  - [Air transport of patients: analysis of scientific knowledge].
AB  - This bibliographic research aimed to characterize scientific production on air
      patient transport in indexed databases. Eighty-three references were found, 76 in
      Medline, between 1997 and 2009, and four in Lilacs, between 1999 and 2007. More
      publications were found in 2001 and qualitative studies were the most prevalent.
      The most evident thematic tendency in Lilacs was education and research, against
      air transport nursing in Medline. The lack of regulation on nurse's tasks on
      board is highlighted, as well as the importance of including contents on
      aerospace nursing in undergraduate and graduate courses. Many gaps remain in
      knowledge production about the theme. Research analyzing this interface qualifies
      aerospace nursing care.

PMID- 22664614
TI  - [Buberian philosophy and the Brazilian stricto sensu postgraduate production:
      integrative review].
AB  - This integrative review aimed to characterize the knowledge production of the
      Brazilian Stricto Sensu postgraduate programs, developed in the light of Martin
      Buber's philosophy. Data were collected from CAPES (Coordination for the
      Improvement of Higher Education Personnel) Data Bank and the sample consisted of
      66 productions. Most of the studies were developed in Education and Psychology
      Programs, and carried out between 2003 and 2007. Most of them were produced in
      the Southeastern region. The main focus was on the teaching-learning process and
      human sexuality. One concludes that, due to its broadness and complexity, this
      referential has assisted different areas of knowledge, and subsidizing distinct
      objects of investigation. In addition, it represents an alternative to health and
      to nursing for the development of relational-dialogical and humanistic care.

PMID- 22664615
TI  - [Data standards, terminology and classification systems for caring in health and
      nursing].
AB  - Information is essential for nursing care because nurses in subsidizing clinical
      decision making for the resolution and reduction of health problems. This review
      integrative study identified publications in national and international journals
      the major data standards, terminologies and classification systems used in health
      care and nursing. The research was conducted on MEDLINE, CINAHL and SCIELO using
      the keywords: Information Systems, Nursing Informatics, Medical Informatics,
      Computerized Medical Records Systems, Terminology and Nomenclature of Medicine
      Systematized. It was selected 91 articles which were analyzed in two empirical
      categories: "data standards for health care and nursing" and "terminologies and
      classification systems in nursing" From the various data standards, terminologies
      and classification systems, it is important that nursing take ownership of them
      aiming to improve and renew the quality of care.

PMID- 22664616
TI  - [Conceptual analysis: methodological considerations].
AB  - Concepts are terms referring to phenomena that occur in nature or in thought,
      which are essential in developing research, as well as in the construction of
      theories. To fulfill this role in the construction of scientific knowledge, it is
      appropriate for them to be reviewed periodically, aiming mainly at its
      improvement. Despite the existence of different models of conceptual analysis,
      this methodology, in general, has not been well understood by nursing, especially
      in our reality. Therefore, in this article, of reflection, we describe some
      methodological considerations, including a practical approach on the methods
      proposed by Walker and Avant, Rodgers and Schwartz-Barcott and Kim, in order to
      give nurses greater understanding of this process.

PMID- 22664617
TI  - [Case study as a strategy for teaching the nursing process and the use of
      standardized language].
AB  - The Nursing education is still strongly related to the biomedical model, although
      there were efforts to structure a Nursing perspective in this context. This paper
      aims to describe an experience of teaching, which used the case study to discuss
      Nursing process, care and use of standardized language. This experience was
      developed with 35 students at the fifth semester of nursing undergraduate at a
      public university in Sao Paulo, Brazil. This teaching strategy had limitations
      and challenges related to students' participation, but it was more interesting
      for them when compared to lectures because it have made them feel like subjects
      in the teaching-learning process and co-responsible for own formation.

PMID- 22664618
TI  - [Construction of educational software about personality disorders].
AB  - The study describes the experience of building educational software in the area
      of mental health. The software was developed to enable the nursing student
      identify personality disorders. In this process, we applied the pedagogical
      framework of Vygotsky and the theoretical framework of the diagnostic criteria
      defined by DSM-IV. From these references were identified personality disorders
      characters in stories and / or children's movies. The software development bank
      was built with multimedia graphics data, sound and explanatory. The software
      developed like educational game like questions with increasing levels of
      difficulty. The software was developed with Microsoft Office PowerPoint 2007. It
      is believed in the validity of this strategy for teaching-learning to the area of
      mental health nursing.

PMID- 22664620
TI  - We can't afford to be laggards.

PMID- 22664619
TI  - Mapping molecular diffusion in the plasma membrane by Multiple-Target Tracing
      (MTT).
AB  - Our goal is to obtain a comprehensive description of molecular processes
      occurring at cellular membranes in different biological functions. We aim at
      characterizing the complex organization and dynamics of the plasma membrane at
      single-molecule level, by developing analytic tools dedicated to Single-Particle
      Tracking (SPT) at high density: Multiple-Target Tracing (MTT). Single-molecule
      videomicroscopy, offering millisecond and nanometric resolution, allows a
      detailed representation of membrane organization by accurately mapping
      descriptors such as cell receptors localization, mobility, confinement or
      interactions. We revisited SPT, both experimentally and algorithmically.
      Experimental aspects included optimizing setup and cell labeling, with a
      particular emphasis on reaching the highest possible labeling density, in order
      to provide a dynamic snapshot of molecular dynamics as it occurs within the
      membrane. Algorithmic issues concerned each step used for rebuilding
      trajectories: peaks detection, estimation and reconnection, addressed by specific
      tools from image analysis. Implementing deflation after detection allows rescuing
      peaks initially hidden by neighboring, stronger peaks. Of note, improving
      detection directly impacts reconnection, by reducing gaps within trajectories.
      Performances have been evaluated using Monte-Carlo simulations for various
      labeling density and noise values, which typically represent the two major
      limitations for parallel measurements at high spatiotemporal resolution. The
      nanometric accuracy obtained for single molecules, using either successive on/off
      photoswitching or non-linear optics, can deliver exhaustive observations. This is
      the basis of nanoscopy methods such as STORM, PALM, RESOLFT or STED, which may
      often require imaging fixed samples. The central task is the detection and
      estimation of diffraction-limited peaks emanating from single-molecules. Hence,
      providing adequate assumptions such as handling a constant positional accuracy
      instead of Brownian motion, MTT is straightforwardly suited for nanoscopic
      analyses. Furthermore, MTT can fundamentally be used at any scale: not only for
      molecules, but also for cells or animals, for instance. Hence, MTT is a powerful
      tracking algorithm that finds applications at molecular and cellular scales.

PMID- 22664621
TI  - On ne peut se permettre d'accuser du retard.

PMID- 22664622
TI  - Grounded, yet reaching for the stars: The growth of the CUA.

PMID- 22664623
TI  - Bien ancree, mais a la conquete de nouveaux sommets : la croissance de l'AUC.

PMID- 22664624
TI  - Status of robotic-assisted surgery among Canadian urology residents.
AB  - BACKGROUND: Robotic-assisted surgery (RAS) has been rapidly adopted in urology,
      especially in the United States. Although less prevalent in Canada, RAS is a
      growing and controversial field that has implications for resident training. We
      report on the status and perception of RAS among Canadian urology residents.
      METHODS: : All Canadian urology residents from anglophone programs were contacted
      by email and asked to participate in an online survey. Current resident exposure
      to, and perception of, RAS was assessed. RESULTS: : Of the residents contacted (n
      = 128), 50 (39%) completed the survey. Of the respondents, 52% have been involved
      in RAS. Those who have not been involved in RAS express lower interest and lesser
      knowledge of RAS. Ninety-two percent of respondents feel the use of RAS will
      increase, although only 29% feel this is feasible in Canada. Just 24% and 36%
      feel RAS to be superior to open and laparoscopic techniques, respectively. Sixty
      eight percent of residents in programs with a robot viewed it as detrimental to
      training, whereas 81% of residents in programs without one viewed its absence to
      either have no impact, or even be beneficial. Both groups expressed a desire for
      more experience with RAS. CONCLUSION: : The resident experience with respect to
      RAS is mixed. Overall, residents view RAS as an expanding field with potentially
      negative impacts on their present training, although they appear to desire the
      acquisition of more experience in RAS. We plan to monitor the evolution of these
      perceptions over next four years.

PMID- 22664625
TI  - Establishing milestones in urology training: A survey of the Canadian Academy of
      Urological Surgeons.
AB  - BACKGROUND: : At the current time, technical skills are not directly evaluated by
      the Royal College of Physicians and Surgeons of Canada (RCPSC) as part of the
      certification process in urology. Rather, the RCPSC relies on the evaluation of
      Program Directors to ensure that trainees have acquired the necessary surgical
      skills. METHODS: : An electronic survey was sent out to the members of the
      Canadian Academy of Urological Surgeons (CAUS), including the 13 Canadian urology
      program directors, to assess the teaching and evaluation of technical skills of
      urology trainees. RESULTS: : The response rate was 37% (33/89), including 8 of
      the 13 (62%) Program Directors from across Canada. For the teaching of technical
      skills, most programs had access to live animal laboratories (69%), dedicated
      teaching time in simulation (59%) and physical training models (59%). Most relied
      on voluntary faculty. There was a wide variety of structured evaluations for
      technical skills used across programs, while 36% of respondents did not use
      structured evaluations. For trainees with deficiencies in technical skills, 67%
      of programs offered extra operative time with designated faculty, 26% offered
      additional simulation focused on the deficiency and 19% offered faculty tutorial
      sessions. CONCLUSION: : Among Canadian urology residency programs, there is
      considerable variability in the assessment of technical skills of trainees.
      Standardized objective assessment tools would help ensure that all trainees have
      acquired adequate surgical proficiency to operate independently.

PMID- 22664626
TI  - Urology residency training: Time to enter the 21st century.

PMID- 22664627
TI  - Duplicate publications: A sample of redundancy in the Journal of Urology.
AB  - PURPOSE: : Redundant publications occur when authors publish a partial or
      complete duplicate of data from an existing manuscript. The push for academic
      advancement in medicine may result in redundant publications that erode the
      quality of literature. We sampled the extent of redundancy within the Journal of
      Urology. METHODS: : Original articles published in the Journal of Urology in 2006
      were reviewed. MEDLINE was used to identify suspected duplicate publications by
      combining the last names of the first, second and last authors with keywords
      provided by the article. Results were limited to 2004 to 2008. Two investigators
      reviewed the suspected duplicate publications and classified them as duplicate,
      probable duplicate and salami-slicing. RESULTS: : We screened 723 original
      articles. Of these original articles, 13 (1.8%) had some form of redundancy. One
      (0.1%) original article had a duplicate article, 5 (0.7%) original articles had
      probable duplicates, and 7 (1%) original articles were salami-sliced. The
      proportion of redundant articles published prior to, and following, their 2006
      index article was 5/13 (38.5%) and 7/13 (53.8%), respectively. One duplicate
      (7.7%) was published in the same month as its index. CONCLUSION: : Detection of
      redundant publications is a laborious process for reviewers and editors. This
      sampling of the Journal of Urology revealed that the duplication rate in this
      journal is small, but significant. Further assessment of the urological
      literature is warranted.

PMID- 22664628
TI  - Ethics in publishing.

PMID- 22664629
TI  - Comparison of serum testosterone levels in prostate cancer patients receiving
      LHRH agonist therapy with or without the removal of the prostate.
AB  - INTRODUCTION: : The prostate secretes enzymes and nutrients to promote sperm
      motility. Recent reports suggest that the prostate may also secrete testosterone,
      which is believed to be a fuel for prostate tumour growth. The aim of this study
      was to determine if a difference in serum testosterone levels exists between men
      on luteinizing hormone releasing-hormone (LHRH) agonists who have undergone
      radical prostatectomy, radiation or hormone therapy as primary prostate cancer
      treatment. METHODS: : Serum testosterone levels were evaluated in 165 consecutive
      prostate cancer patients using LHRH analogues for >3 months. We excluded patients
      receiving either radiation or chemotherapy at time of time of testosterone
      measurement. Patients were classified based on primary treatment: (1) radical
      prostatectomy; (2) radiation; or (3) primary hormone therapy. We used one-way
      ANOVA to compare testosterone levels. Pearson correlation was used to correlate
      testosterone with prostate-specific antigen (PSA) and time on LHRH agonists.
      Multivariable linear regression was used to predict serum testosterone levels.
      RESULTS: : The median (interquartile range) serum testosterone levels were 1.4 (1
      1.9), 1.3 (1-1.625) and 1.25 (0.9-1.525) nmol/L for radical prostatectomy,
      radiation and primary hormone therapy groups, respectively. There was no
      statistically significant difference in testosterone levels between the groups (p
      = 0.3). No correlation was found between testosterone and PSA levels or time on
      LHRH (r = 0.02 and r = 0.01), respectively. Multivariable linear regression
      showed that none of the clinical variables were predictors of serum testosterone
      levels. CONCLUSION: : Our study suggests that primary treatment does not affect
      serum testosterone levels among men using LHRH analogues.

PMID- 22664630
TI  - What determines testosterone levels?

PMID- 22664631
TI  - Prostate cancer screening: Attitudes and practices of family physicians in
      Ontario.
AB  - INTRODUCTION: : The utility of prostate cancer screening is controversial. We
      sought to determine whether Ontario's family physicians believe it is beneficial
      and to characterize their screening protocols. METHODS: : A survey was developed
      with input from urologists, family physicians and the Ontario Medical
      Association's Section on General and Family Practice. Questions covered three
      domains: (1) demographics, (2) beliefs about screening utility and (3) screening
      practices. All 7302 family physicians in Ontario were invited by email to
      complete the online survey. RESULTS: : A total of 969 physicians completed the
      survey; 955 (52.0% male, 48.0% female) were included. Most (80.97%) use prostate
      specific antigen (PSA) and digital rectal examination (DRE) for screening; 9.4%
      use DRE alone and 7.15% PSA. Of the respondents, 8.3% do not offer prostate
      cancer screening. Most physicians begin offering screening at age 50 (72.9%) and
      stop at ages 70 or 80 (68.4%); 17.9% offer lifelong screening. In response to the
      statement "screening with DRE provides a survival benefit," 37.6% and 32.6 agreed
      and disagreed, respectively. For "screening with PSA provides a survival
      benefit," 43.3% agreed and 31.0% disagreed. For the statement "the benefits of
      prostate cancer screening outweigh the risks," 51.4% agreed and 22.0% disagreed.
      DISCUSSION: : Although 91.7% of respondents offer prostate cancer screening, they
      are divided over its utility. Only 51.4% were convinced that the benefits
      outweighed the harms. There is significant variability between physicians'
      screening protocols. A limitation of this study is the possibility of selection
      bias. Nevertheless, this is the largest sample of Ontario family physicians ever
      surveyed about prostate cancer screening and highlights divergent physician
      practices and a need for more conclusive evidence on screening utility.

PMID- 22664632
TI  - The confusion surrounding prostate cancer screening faced by family physicians.

PMID- 22664633
TI  - The best method for dose escalation: Prostate brachytherapy.

PMID- 22664634
TI  - Be it resolved that in the modern era, the best method for dose escalation is
      brachytherapy: The con position.

PMID- 22664635
TI  - In memoriam.

PMID- 22664636
TI  - Rapid turnover of glycogen in memory formation.
AB  - The influence of noradrenaline acting at alpha(2)-AR and beta(2)-ARs on the
      turnover of glycogen after learning has been investigated. The role of glycogen
      turnover in memory formation was examined using weakly-reinforced, single trial
      bead discrimination training in day-old domestic chickens. This study follows our
      previous work that focused on the need for glycogen breakdown (glycogenolysis)
      during learning. Inhibition of glycogenolysis by 1,4-dideoxy-1,4-imino-D
      arabinitol (DAB) prevented the consolidation of strongly-reinforced learning and
      inhibited memory. The action of DAB could be prevented by stimulating
      glycogenolysis with the selective beta(2)-AR agonist, zinterol. Stimulation of
      alpha(2)-ARs has been shown to lead to an increase in the turnover and synthesis
      of glycogen. In the present study, we examined the effect of inhibition of
      alpha(2)-AR stimulated glycogen turnover (measured as(14)C-glucose incorporation
      into glycogen) on the ability of zinterol to promote the consolidation of weakly
      reinforced memory. In astrocytes, the selective alpha(2)-AR agonist clonidine
      stimulated (14)C-glucose incorporation into glycogen in chick astrocytes and this
      was inhibited by the selective alpha(2)-AR antagonist, ARC239. The critical
      importance of the timing of ARC239 injection relative to training and
      intracerebral administration of zinterol was examined. It is concluded that our
      data provides evidence for a readily accessible labile pool of glycogen in brain
      astrocytes. If glycogen synthesis is inhibited, the can be depleted within 10
      min, thus preventing zinterol from promoting consolidation.

PMID- 22664638
TI  - The PWAPA cassette: Intimate association of a PHD-like finger and a winged-helix
      domain in proteins included in histone-modifying complexes.
AB  - Polycomb complexes function as enforcers of epigenetically repressed state,
      balanced by an antagonist state mediated by Trithorax. Using sensitive methods of
      sequence analysis, we show here that Polycomb-like proteins (PCLs) contain a
      tandem of intimately associated domains, which we named PWAPA and which is also
      present in ASH2L, a member of the Trithorax group. Polycomb-like proteins and
      ASH2L belong to the PCR2 and MLL histone methyltransferase complexes,
      respectively. A PWAPA cassette is also present in ATAC2, a component of the ATAC
      histone acetyltransferase complex. The recently solved structure of the PWAPA
      tandem of ASH2L has revealed that it consist in a PHD-like finger followed by a
      helix-winged-helix (WH) domain, able to bind DNA. The modeling of the 3D
      structure of the different members of the PWAPA family suggests that the PHD-like
      finger might be able, at least for some proteins of the family, to bind
      methylated marks on histones. The PWAPA PHD/WH cassette might thus be involved in
      the combined recognition of DNA and specific (perhaps methylation) mark(s) on
      histones, thereby allowing the recruitment of specific chromatin-modifying
      activities at these sites. The observations reported here should help to unravel
      the exact role played by the PWAPA cassette in the different proteins of the
      PWAPA family, and especially in the antagonistic activities of PcG and TrxG
      proteins.

PMID- 22664637
TI  - A model of flux regulation in the cholesterol biosynthesis pathway: Immune
      mediated graduated flux reduction versus statin-like led stepped flux reduction.
AB  - The cholesterol biosynthesis pathway has recently been shown to play an important
      role in the innate immune response to viral infection with host protection
      occurring through a coordinate down regulation of the enzymes catalysing each
      metabolic step. In contrast, statin based drugs, which form the principle
      pharmaceutical agents for decreasing the activity of this pathway, target a
      single enzyme. Here, we build an ordinary differential equation model of the
      cholesterol biosynthesis pathway in order to investigate how the two regulatory
      strategies impact upon the behaviour of the pathway. We employ a modest set of
      assumptions: that the pathway operates away from saturation, that each metabolite
      is involved in multiple cellular interactions and that mRNA levels reflect enzyme
      concentrations. Using data taken from primary bone marrow derived macrophage
      cells infected with murine cytomegalovirus or treated with IFNgamma, we show
      that, under these assumptions, coordinate down-regulation of enzyme activity
      imparts a graduated reduction in flux along the pathway. In contrast, modelling a
      statin-like treatment that achieves the same degree of down-regulation in
      cholesterol production, we show that this delivers a step change in flux along
      the pathway. The graduated reduction mediated by physiological coordinate
      regulation of multiple enzymes supports a mechanism that allows a greater level
      of specificity, altering cholesterol levels with less impact upon interactions
      branching from the pathway, than pharmacological step reductions. We argue that
      coordinate regulation is likely to show a long-term evolutionary advantage over
      single enzyme regulation. Finally, the results from our models have implications
      for future pharmaceutical therapies intended to target cholesterol production
      with greater specificity and fewer off target effects, suggesting that this can
      be achieved by mimicking the coordinated down-regulation observed in
      immunological responses.

PMID- 22664639
TI  - Impact of synergistic polymorphisms in adrenergic receptor-related genes and
      cardiovascular events in patients with dilated cardiomyopathy.
AB  - BACKGROUND: Sustained cardiac adrenergic stimulation has been implicated in the
      progression of cardiovascular events in patients with dilated cardiomyopathy
      (DCM). Our group hypothesized that a combination of polymorphisms that result in
      increased synaptic norepinephrine release and enhanced receptor function would
      predispose patients with DCM to cardiovascular events. The effect of
      polymorphisms in adrenergic receptor-related genes on cardiovascular event-free
      survival in patients with idiopathic DCM was evaluated. METHODS AND RESULTS:
      Genotyping at 3 loci (ADRB1 Ser49Gly and Arg389Gly, and NET T-182C) was performed
      in 83 patients with DCM. Patients were followed prospectively to the endpoint of
      cardiovascular events (mean follow-up, 45 months). Cardiovascular events were
      defined as cardiac death and emergent hospitalization as a result of congestive
      heart failure, arrhythmia, and cerebrovascular events. Analyses were conducted
      based on the number of predicted risk genotypes a patient carried. The ADRB1
      Ser49 allele carrier, ADRB1 Arg389 allele carrier, and NET-182CC genotype were
      defined as the predicted risk genotypes. Cardiovascular event-free survival was
      compared based on the number of predicted risk genotypes. Cardiovascular event
      free survival was significantly better in patients with fewer than 3 predicted
      risk genotypes than in those with 3 predicted risk genotypes. CONCLUSIONS:
      Genotyping at these 3 loci might be a useful approach for identification of
      patients with DCM at risk for cardiovascular events.

PMID- 22664640
TI  - Joint effects of genetic variants in multiple loci on the risk of coronary artery
      disease in Chinese Han subjects.
AB  - BACKGROUND: The aim of the present study was to explore risk variants for
      coronary artery disease (CAD) and to evaluate their joint effects (quantified by
      genetic risk score; GRS) on the discrimination of CAD in a Chinese Han sample.
      METHODS AND RESULTS: An association analysis of 91 single nucleotide
      polymorphisms (SNPs) with CAD risk was undertaken in 1,007 CAD patients and 889
      healthy controls. Two GRSs, counted GRS (cGRS) and weighted GRS (wGRS), were
      calculated using the significant SNPs, and their discriminant power for CAD was
      assessed using receiver-operating characteristic (ROC) curve analysis. Eight SNPs
      (rs11206510, rs10118757, rs2383206, rs501120, rs2075292, rs174547, rs173539, and
      rs255052) were nominally significantly associated with CAD (P<0.05), and 5 of
      them were newly reported. The GRSs derived from the 8 SNPs improved the
      discrimination of CAD compared to that using 4 conventional risk factors (P=0.002
      for cGRS and P=0.009 for wGRS). After 10-fold cross-validation 100 times, the
      average areas under the curve were 0.668 (95% confidence interval [CI]: 0.667
      0.669), 0.686 (95% CI: 0.685-0.687) and 0.690 (95% CI: 0.689-0.691) for models
      with conventional risk factors only, conventional risk factors plus cGRS, and
      conventional risk factors plus wGRS, respectively. CONCLUSIONS: A multigenic GRS,
      generated by combining multiple gene variants, can improve discrimination of CAD,
      thereby confirming the joint effects of these gene variants on CAD in this
      Chinese Han population.

PMID- 22664641
TI  - Beyond horizon: epicardial atrial tachycardia mimicking typical atrial flutter.

PMID- 22664642
TI  - Molecular phylogeny and dating of Asteliaceae (Asparagales): Astelia s.l.
      evolution provides insight into the Oligocene history of New Zealand.
AB  - Asteliaceae (4 genera, 36 species) are found on both continents and island
      archipelagos in the southern hemisphere and across the Pacific. The
      circumscription of Asteliaceae and intrageneric relationships are poorly
      understood. We generated a phylogeny including all genera and 99% of the species
      using DNA sequence data from chloroplast (trnL, psbA-trnH, rps16, and petL-psbE)
      and nuclear (NIA-i3) regions. Relaxed clock methods were applied to infer the age
      of the family and the timing of cladogenic events. Generic delimitations change
      as a result of this study. Collospermum is nested within Astelia and is
      recognized here only at the subgeneric level. Further, Astelia subgenera Astelia,
      Asteliopsis, and Tricella are paraphyletic and to achieve monophyly their
      recircumscriptions are proposed. Despite the presence of Asteliaceae taxa on
      multiple Gondwanan landmasses and proposed Cretaceous origins for the family,
      radiation of genera was during the Tertiary. The largest and oldest genus,
      Astelia s.l. (including Collospermum), radiated around the Eocene/Oligocene
      boundary (ca. 34.2 million years ago (Ma)). Astelia s.l. subgenera diverged from
      the Oligocene/Miocene boundary onwards (<24.0 Ma). These dates suggest that
      current distributions are most likely to be the result of long-distance
      dispersal. Alpine taxa in New Zealand and Australia radiated during the Late
      Miocene/Pliocene. These results are congruent with Astelia micro- and macro
      fossil data and suggest that Astelia s.l. either persisted in New Zealand during
      the proposed Oligocene marine transgression or dispersed from Australia after the
      subsequent expansion of terrestrial habitat.

PMID- 22664643
TI  - Adiponectin inhibits the generation of reactive oxygen species induced by high
      glucose and promotes endothelial NO synthase formation in human mesangial cells.
AB  - The aim of this study was to investigate the effects of adiponectin (ADPN) on
      high glucose (HG)-induced reactive oxygen species (ROS) and the formation of
      endothelial nitric oxide (NO) synthase (eNOS) in human glomerular mesangial cells
      (HMCs), as well as to determine which signaling pathways are modulated by ADPN
      and the mechanisms involved. HMCs cultured in vitro were randomly divided into 4
      groups: the control, HG, HG + globular adiponectin (gAd) and HG + gAd + adenine
      arabinoside (AraA). The generation of ROS was detected using a fluorescent probe.
      The mRNA expression and protein levels of eNOS were measured by RT-PCR and
      western blot analysis, respectively. The phosphorylation of AMP-activated protein
      kinase (AMPK) was assessed by western blot analysis. HMCs treated with ADPN
      revealed the time-dependent phosphorylation of AMPK. The treatment of HMCs with
      HG resulted in increased release of ROS and decreased expression of eNOS compared
      to the control group (p<0.05). Cells treated with ADPN showed a decrease in HG
      induced ROS (p<0.05) and an upregulated eNOS expression. The effects of gAd were
      partly blocked by the AMPK inhibitor, AraA. The results from the present study
      show that ADPN inhibits the generation of HG-induced ROS in HMCs; it also
      stimulates eNOS activity, which has a protective effect. The mechanism partly
      occurs through the stimulation of the AMPK signaling pathway.

PMID- 22664644
TI  - The prevalence and influence of self-reported conflicts of interest by editorial
      authors of phase III cancer trials.
AB  - PURPOSE: To assess the frequency with which editorial authors report personal
      conflict of interest and investigate a possible association between the presence
      of such conflicts and favorable opinion. METHODS: Eligible studies were
      editorials of phase III clinical trials of antitumor drugs or symptom management
      published from January 2007 to December 2009 in four top oncology journals. Data
      from the editorials were collected and each editorial opinion was classified as
      favorable, neutral or unfavorable with respect to the experimental therapy.
      RESULTS: Fifty-four editorials were included: 23 (43%) reported at least one
      conflict of interest, with the most frequent one being consultancy fees.
      Conclusions of editorial authors were classified as favorable in 18 editorials
      (33%). Sensitivity analysis found an association between self-reported conflict
      of interest of the editorial author and editorial favorable opinion (RR:2.7; 95%
      CI 1.2-6.1; p=0.019). DISCUSSION: Besides the high proportion of conflict of
      interest among editorial authors discussing phase III clinical trials, study
      interpretation may be influenced by their financial relationships with industry.

PMID- 22664645
TI  - Longitudinal Pediatric Palliative Care: Quality of Life & Spiritual Struggle
      (FACE): design and methods.
AB  - As life expectancy increases for adolescents ever diagnosed with AIDS due to
      treatment advances, the optimum timing of advance care planning is unclear. Left
      unprepared for end-of-life (EOL) decisions, families may encounter
      miscommunication and disagreements, resulting in families being charged with
      neglect, court battles and even legislative intervention. Advanced care planning
      (ACP) is a valuable tool rarely used with adolescents. The Longitudinal Pediatric
      Palliative Care: Quality of Life & Spiritual Struggle study is a two-arm,
      randomized controlled trial assessing the effectiveness of a disease specific
      FAmily CEntered (FACE) advanced care planning intervention model among
      adolescents diagnosed with AIDS, aimed at relieving psychological, spiritual, and
      physical suffering, while maximizing quality of life through facilitated
      conversations about ACP. Participants will include 130 eligible dyads (adolescent
      and family decision-maker) from four urban cities in the United States,
      randomized to either the FACE intervention or a Healthy Living Control. Three 60
      minute sessions will be conducted at weekly intervals. The dyads will be assessed
      at baseline as well as 3-, 6-, 12-, and 18-month post-intervention. The primary
      outcome measures will be in congruence with EOL treatment preferences, decisional
      conflict, and quality of communication. The mediating and moderating effects of
      threat appraisal, HAART adherence, and spiritual struggle on the relationships
      among FACE and quality of life and hospitalization/dialysis use will also be
      assessed. This study will be the first longitudinal study of an AIDS-specific
      model of ACP with adolescents. If successful, this intervention could quickly
      translate into clinical practice.

PMID- 22664646
TI  - Reporting of cause-specific treatment effects in cancer clinical trials with
      competing risks: a systematic review.
AB  - BACKGROUND: Separate analysis of cause-specific treatment effects is important
      for interpreting results of randomized trials. We sought to determine the extent
      to which cause-specific effects on primary events are reported in contemporary
      randomized controlled trials in oncology. METHODS: We screened 833 randomized
      trials published in eight leading medical journals between January 2006 and
      December 2009. We excluded prevention studies (n=52), secondary reports (n=100),
      and one retracted study. Analysis was further restricted to 116 trials in non
      metastatic/recurrent cancer that used an event-free survival primary endpoint.
      For each study included in the analysis, we evaluated whether treatment effects
      on both cancer and non-cancer events comprising the primary endpoint were
      reported separately and whether statistical analysis was provided. RESULTS: Of
      the 116 randomized trials, 47 (40%; 95% confidence interval (CI), 32-50%)
      reported effects on both cancer and non-cancer events comprising the primary
      endpoint, with statistical analysis provided in 13 (11%; 95% CI, 7-19%). Twenty
      six trials (22%; 95% CI, 15-31%) reported effects on cancer but not non-cancer
      events, with statistical analysis provided in 11 (9%; 95% CI, 5-17%). In 43
      studies (37%; 95% CI, 28-47%), no effects on cancer-specific components of the
      primary endpoint were given. Of these, 33 studies (28%; 95% CI, 21-38%) did
      report effects on some cancer-specific event, while ten (9%; 95% CI, 4-16%) did
      not report effects of treatment on any cancer event. DISCUSSION: Many randomized
      trials in oncology do not report cause-specific effects on primary events.
      Increased specificity is needed in the design and reporting of cancer clinical
      trials.

PMID- 22664647
TI  - Weight management by phone conference call: a comparison with a traditional face
      to-face clinic. Rationale and design for a randomized equivalence trial.
AB  - State-of-the-art treatment for weight management consists of a behavioral
      intervention to facilitate decreased energy intake and increased physical
      activity. These interventions are typically delivered face-to-face (FTF) by a
      health educator to a small group of participants. There are numerous barriers to
      participation in FTF clinics including availability, scheduling, the expense and
      time required to travel to the clinic site, and possible need for dependent care.
      Weight management clinics delivered by conference call have the potential to
      diminish or eliminate these barriers. The conference call approach may also
      reduce burden on providers, who could conduct clinic groups from almost any
      location without the expenses associated with maintaining FTF clinic space. A
      randomized trial will be conducted in 395 overweight/obese adults (BMI 25-39.9
      kg/m(2)) to determine if weight loss (6 months) and weight maintenance (12
      months) are equivalent between weight management interventions utilizing
      behavioral strategies and pre-packaged meals delivered by either a conference
      call or the traditional FTF approach. The primary outcome, body weight, will be
      assessed at baseline, 6, 12 and 18 months. Secondary outcomes including waist
      circumference, energy and macronutrient intake, and physical activity and will be
      assessed on the same schedule. In addition, a cost analysis and extensive process
      evaluation will be completed.

PMID- 22664648
TI  - An EMR-based tool to support collaborative planning for medication use among
      adults with diabetes: design of a multi-site randomized control trial.
AB  - Patients with type II diabetes often struggle with self-care, including adhering
      to complex medication regimens and managing their blood glucose levels.
      Medication nonadherence in this population reflects many factors, including a gap
      between the demands of taking medication and the limited literacy and cognitive
      resources that many patients bring to this task. This gap is exacerbated by a
      lack of health system support, such as inadequate patient-provider collaboration.
      The goal of our project is to improve self-management of medications and related
      health outcomes by providing system support. The MedtableTM is an Electronic
      Medical Record (EMR)-integrated tool designed to support patient-provider
      collaboration needed for medication management. It helps providers and patients
      work together to create effective medication schedules that are easy to
      implement. We describe the development and initial evaluation of the tool, as
      well as the process of integrating it with an EMR system in general internal
      medicine clinics. A planned evaluation study will investigate whether an
      intervention centered on the MedtableTM improves medication knowledge, adherence,
      and health outcomes relative to a usual care control condition among type II
      diabetic patients struggling to manage multiple medications.

PMID- 22664649
TI  - Factors associated with attaining coaching goals during an intervention to
      improve child asthma care.
AB  - PURPOSE: To examine parent and child characteristics associated with engagement
      in a coaching intervention to improve pediatric asthma care and factors
      associated with readiness to adopt and maintain targeted asthma management
      behaviors. METHODS: Using methods based on the Transtheoretical Model, trained
      lay coaches worked with 120 parents of children with asthma promoting adoption
      and maintenance of asthma management strategies (behaviors). Coaches assigned
      stage-of-change (on continuum: pre-contemplation, contemplation, preparation,
      action, maintenance) for each behavior every time it was discussed. Improvement
      in stage-of-change was analyzed for association with characteristics of the
      participants (parents and children) and coaching processes. RESULTS: Having more
      coach contacts was associated with earlier first contact (p<0.001), fewer
      attempts per successful contact (p<0.001), prior asthma hospitalization
      (p=0.021), more intruding events (p<0.001), and less social support (p=0.048). In
      univariable models, three factors were associated with forward movement at least
      one stage for all three behaviors: more coach contacts overall, fewer attempts
      per successful contact, and more discussion/staging episodes for the particular
      behavior. In multivariable models adjusting for characteristics of participants
      and coaching process, the strongest predictor of any forward stage movement for
      each behavior was having more contacts (p<0.05). CONCLUSIONS: Improvement in
      readiness to adopt and maintain asthma management behaviors was mostly associated
      with factors reflecting more engagement of participants in the program. Similar
      coaching interventions should focus on early and frequent contacts to achieve
      intervention goals, recognizing that parents of children with less severe disease
      and who have more social support may be more difficult to engage.

PMID- 22664650
TI  - Decreased endothelial progenitor cells and increased serum glycated albumin are
      independently correlated with plaque-forming carotid artery atherosclerosis in
      type 2 diabetes patients without documented ischemic disease.
AB  - BACKGROUND: The aim of the present study was to investigate the serum levels of
      endothelial progenitor cells (EPCs) in type 2 diabetic patients without
      documented ischemic disease and the association between EPCs and atherosclerotic
      plaque formation in the carotid artery. METHODS AND RESULTS: A clinic-based,
      prospective study of type 2 diabetic patients was conducted. A total of 73
      subjects were enrolled in this study after cardiac magnetic resonance imaging and
      ankle-brachial index measurements to exclude patients with ischemic disease.
      Plaque formation in the carotid artery was measured on ultrasonography.
      Circulating EPCs (CD34(+)/CD133(+)/CD309(+) cells) were counted on flow
      cytometry. Compared to subjects without carotid artery plaques, patients with
      plaques were significantly older (P=0.006) and had decreased EPC count (P=0.027).
      Serum glycated albumin (GA) level and the GA/glycated hemoglobin ratio tended to
      decrease in patients with plaques (P=0.091 and 0.067, respectively). Other
      cardiovascular disease risk factors were not significantly different between the
      2 groups. On binary logistic regression analysis old age, low EPC count, and high
      serum GA level were independently correlated with carotid artery plaque
      formation. CONCLUSIONS: EPC count and serum GA level appear to be a protective
      and an aggravating factor for endothelial damage, respectively, and therefore, a
      reduced EPC count or an increased GA level results in atherosclerotic plaque
      formation in type 2 diabetic patients. 

PMID- 22664651
TI  - Arsenic affects essential and non-essential amino acids differentially in rice
      grains: inadequacy of amino acids in rice based diet.
AB  - Recent breakthroughs in rice arsenic (As) research demonstrate that As
      accumulation significantly affects trace nutrients in rice grain. In the present
      study we analyzed the amino acid (AA) profile of sixteen rice genotypes differing
      in grain As accumulation, grown at three sites with different soil As
      concentrations, in ascending order, Chinsurah<Purbosthali<Birnagar. Grain As
      accumulation negatively correlated with essential amino acids (EAAs) which were
      more prominent in high As accumulating rice genotypes (HAARGs). Conversely, non
      essential amino acids (NEAAs) showed an increase in low As accumulating rice
      genotypes (LAARGs) but a decrease in HAARGs. EAAs like isoleucine, leucine,
      valine, phenylalanine, and tyrosine also decreased in most of the genotypes.
      NEAAs like glutamic acid, glycine, proline, and histidine showed an increase in
      all LAARGs. Likewise, sulfur containing AAs (methionine and cysteine) increased
      in LAARGs but decreased in HAARGs. Among NEAAs in HAARGs, only arginine and
      serine showed some induction in most of the genotypes. At the highest As site
      (Birnagar) total EAAs and NEAAs show significant reduction in HAARGs compared to
      LAARGs. The study concluded that As accumulation in rice grain alters EAAs and
      NEAAs differentially, and reduction was more pronounced in HAARGs than in LAARGs.
      Thus, As tainted rice limits required levels of AAs in rice based diets and
      therefore cannot alone fulfill the recommended daily intake (RDI) of AAs.

PMID- 22664652
TI  - Patient and health care provider discussions about the risks of medical imaging:
      not ready for prime time.

PMID- 22664653
TI  - Inhibition of Bcl-xL by ABT-737 enhances chemotherapy sensitivity in
      neurofibromatosis type 1-associated malignant peripheral nerve sheath tumor
      cells.
AB  - Neurofibromatosis type 1 (NF1) is one of the most commonly inherited autosomal
      dominant disorders. The malignant peripheral nerve sheath tumor (MPNST) is a
      major cause of mortality in patients with NF1. In this study, we found that
      overexpression of Bcl-xL in the established NF1-associated MPNST cell line and
      primary tissue cultured MPNST cells derived from an NF1 patient was closely
      associated with anticancer drug resistance of the NF1-associated MPNST cells. We
      demonstrated that high expression of Bcl-xL in the MPNST cells was caused by a
      decreased transcriptional expression of the NF1 gene. Downregulation of the NF1
      gene by RNA interference (RNAi) induced an increase in Bcl-xL expression and a
      decrease in its sensitivity to apoptosis in the benign neurofibroma cell line and
      primary normal cells. These results suggest that an alteration of Bcl-xL
      expression levels by somatic expression changes in the NF1 locus may contribute
      to the malignant development of benign tumor tissues or normal tissues to MPNSTs.
      We further demonstrated that either depletion of Bcl-xL expression by RNAi or
      inactivation of Bcl-xL by ABT-737, a mimetic of the BH3-only protein BAD, was
      very effective in sensitizing the MPNST cells to apoptotic cell death by combined
      treatment with the tested anticancer drug doxorubicin. Notably, a low
      concentration of ABT-737 and doxorubicin could effectively induce synergistic
      cytotoxicity in the MPNST cells. These results suggest that pharmacological
      inhibition of Bcl-xL by ABT-737 in combination with doxorubicin can be a
      potential therapeutic strategy for the treatment of NF1-associated MPNSTs.

PMID- 22664654
TI  - 4-hexylresorcinol stimulates the differentiation of SCC-9 cells through the
      suppression of E2F2, E2F3 and Sp3 expression and the promotion of Sp1 expression.
AB  - The dormancy-inducing factors of bacteria inhibit tumor cell growth. In the
      present study, we evaluated the antitumor effects of the dormancy-inducing factor
      4-hexylresorcinol (4-HR) using real-time cell electronic sensing (RT-CES) in SCC
      9 cells (tongue squamous cell carcinoma cells). Treatment with 4-HR suppressed
      the growth of SCC-9 cells in a dose-dependent manner. We used a DNA microarray to
      identify genes that showed a significant change in expression upon 4-HR
      administration in SCC-9 cells. Among the differentially expressed genes, the
      protein expression of several cell proliferation related factors, including E2F1,
      E2F2, E2F3, E2F4, E2F5, E2F6, Sp1 and Sp3, were determined by western blot
      analyses. Treatment with 4-HR strongly suppressed E2F2 and slightly suppressed
      E2F3 but did not change the expression of E2F1, E2F4, E2F5 and E2F6 relative to
      no treatment. Furthermore, 4-HR increased Sp1 expression in a dose-dependent
      manner and decreased Sp3 expression. Therefore, the ratio of Sp1 to Sp3, an
      important driving force of epithelial cell differentiation, was drastically
      increased. Consistent with this observation, 4-HR increased the expression of the
      epithelial cell differentiation markers involucrin and keratin 10. Together, our
      results indicate that 4-HR induces the differentiation of SCC-9 via the
      modulation of the E2F-mediated signaling pathway.

PMID- 22664656
TI  - Effects of experimentally induced maternal hypothyroidism and hyperthyroidism on
      the development of rat offspring: II-the developmental pattern of neurons in
      relation to oxidative stress and antioxidant defense system.
AB  - Excessive concentrations of free radicals in the developing brain may lead to
      neurons maldevelopment and neurons damage and death. Thyroid hormones (THs)
      states play an important role in affecting the modulation of oxidative stress and
      antioxidant defense system. Thus, the objective of this study was to clarify the
      effect of hypothyroidism and hyperthyroidism in rat dams on the neurons
      development of different brain regions of their offspring at several postnatal
      weeks in relation to changes in the oxidative stress and antioxidant defense
      system. The adult female rats were administered methimazole (MMI) in drinking
      water (0.02% w/v) from gestation day 1 to lactation day 21 to induce
      hypothyroidism and exogenous thyroxine (T4) in drinking water (0.002% w/v) beside
      intragastric incubation of 50--200 T4 MUg/kg body weight (b. wt.) to induce
      hyperthyroidism. In normal female rats, the sera total thyroxine (TT4) and total
      triiodothyronine (TT3) levels were detectably increased at day 10 post-partum
      than those at day 10 of pregnancy. Free thyroxine (FT4), free triiodothyronine
      (FT3), thyrotropin (TSH) and growth hormone (GH) concentrations in normal
      offspring were elevated at first, second and third postnatal weeks in an age
      dependent manner. In hypothyroid group, a marked depression was observed in sera
      of dam TT3 and TT4 as well as offspring FT3, FT4 and GH, while there was a
      significant increase in TSH level with the age progress. The reverse pattern to
      latter state was recorded in hyperthyroid group. Concomitantly, in control
      offspring, the rate of neuron development in both cerebellar and cerebral cortex
      was increased in its density and complexity with age progress. This development
      may depend, largely, on THs state. Both maternal hypothyroidism and
      hyperthyroidism caused severe growth retardation in neurons of these regions of
      their offspring from the first to third weeks. Additionally, in normal offspring,
      seven antioxidant enzymes, four non-enzymatic antioxidants and one oxidative
      stress marker (lipid peroxidation, LPO) followed a synchronized course of
      alterations in cerebrum, cerebellum and medulla oblongata. In both thyroid
      states, the oxidative damage has been demonstrated by the increased LPO and
      inhibition of enzymatic and non-enzymatic antioxidants in most examined ages and
      brain regions. These disturbances in the antioxidant defense system led to
      deterioration in the neuronal maturation and development. In conclusion, it can
      be suggested that the maldevelopment of neurons and dendrites in different brain
      regions of offspring of hypothyroid and hyperthyroid mother rat dams may be
      attributed, at least in part, to the excess oxidative stress and deteriorated
      antioxidant defense system in such conditions.

PMID- 22664655
TI  - Hypothalamic expression of snoRNA Snord116 is consistent with a link to the
      hyperphagia and obesity symptoms of Prader-Willi syndrome.
AB  - The hypothalamus is integral to the regulation of body homeostasis, including
      food intake, energy balance, and blood pressure. Dysfunction of the hypothalamus
      has been associated with a broad range of disorders; many of which are sex
      dependent in prevalence. Small nucleolar (sno) RNAs are a group of small RNAs
      located in nucleoli that modulate chemical modifications and maturation of
      ribosomal or other RNAs. Recent data suggest that snoRNA Snord116 is important
      for the pathogenesis of Prader-Willi syndrome (PWS) characterized by hyperphagia
      and obesity. The current study was conducted to assess a potential cellular link
      between Snord116 and phenotypes of PWS. Data from mice revealed Snord116
      expression in the medial hypothalamus, particularly within nuclei that are part
      of feeding circuitry. High expression of Snord116 was evident in the
      paraventricular (PVN) and ventromedial (VMH) nuclei, but particularly prevalent
      in the arcuate nucleus (ARC) according to in situ hybridization. Snord116
      expression level in ventral hypothalamic dissections including ARC was
      significantly greater (by 2-fold) than that in cortex; and its expression level
      in dorsal hypothalamic dissections including PVN was double that in cortex. The
      enhanced expression pattern of Snord116 in hypothalamic nuclei was observed at
      weaning and young adult stages, but less obvious neonatally when expression was
      significantly more widespread. Therefore the expression of Snord116 likely is
      regulated developmentally. These results provide a new lead for understanding the
      mechanism(s) related to hyperphagia and obesity symptoms in PWS patients.

PMID- 22664657
TI  - Blood collection for biochemical analysis in adult zebrafish.
AB  - The zebrafish has been used as an animal model for studies of several human
      diseases. It can serve as a powerful preclinical platform for studies of
      molecular events and therapeutic strategies as well as for evaluating the
      physiological mechanisms of some pathologies. There are relatively few
      publications related to adult zebrafish physiology of organs and systems, which
      may lead researchers to infer that the basic techniques needed to allow the
      exploration of zebrafish systems are lacking. Hematologic biochemical values of
      zebrafish were first reported in 2003 by Murtha and colleagues who employed a
      blood collection technique first described by Jagadeeswaran and colleagues in
      1999. Briefly, blood was collected via a micropipette tip through a lateral
      incision, approximately 0.3 cm in length, in the region of the dorsal aorta.
      Because of the minute dimensions involved, this is a high-precision technique
      requiring a highly skilled practitioner. The same technique was used by the same
      group in another publication in that same year. In 2010, Eames and colleagues
      assessed whole blood glucose levels in zebrafish. They gained access to the blood
      by performing decapitations with scissors and then inserting a heparinized
      microcapillary collection tube into the pectoral articulation. They mention
      difficulties with hemolysis that were solved with an appropriate storage
      temperature based on the work Kilpatrick et al. When attempting to use
      Jagadeeswaran's technique in our laboratory, we found that it was difficult to
      make the incision in precisely the right place as not to allow a significant
      amount of blood to be lost before collection could be started. Recently, Gupta et
      al. described how to dissect adult zebrafish organs, Kinkle et al. described how
      to perform intraperitoneal injections, and Pugach et al. described how to perform
      retro-orbital injections. However, more work is needed to more fully explore
      basic techniques for research in zebrafish. The small size of zebrafish presents
      challenges for researchers using it as an experimental model. Furthermore, given
      this smallness of scale, it is important that simple techniques are developed to
      enable researchers to explore the advantages of the zebrafish model.

PMID- 22664658
TI  - Elastic anisotropy of uniaxial mineralized collagen fibers measured using two
      directional indentation. Effects of hydration state and indentation depth.
AB  - Mineralized turkey leg tendon (MTLT) is an attractive model of mineralized
      collagen fibers, which are also present in bone. Its longitudinal structure is
      advantageous for the relative simplicity in modeling, yet its anisotropic elastic
      properties remain unknown. The aim of this study was to quantify the extent of
      elastic anisotropy of mineralized collagen fibers by using nano- and
      microindentation to probe a number on MTLT samples in two orthogonal directions.
      The large dataset allowed the quantification of the extent of anisotropy,
      depending on the final indentation depth and on the hydration state of the
      sample. Anisotropy was observed to increase with the sample re-hydration process.
      Artifacts of indentation in a transverse direction to the main axis of the
      mineralized tendons in re-hydrated condition were observed. The indentation size
      effect, that is, the increase of the measured elastic properties with decreasing
      sampling volume, reported previously on variety of materials, was also observed
      in MTLT. Indentation work was quantified for both directions of indentation in
      dried and re-hydrated conditions. As hypothesized, MTLT showed a higher extent of
      anisotropy compared to cortical and trabecular bone, presumably due to the
      alignment of mineralized collagen fibers in this tissue.

PMID- 22664659
TI  - A microduplication of the Rubinstein-Taybi region on 16p13.3 in a girl with a
      bilateral complete cleft lip and palate and severe mental retardation.

PMID- 22664660
TI  - Patient with a neurofibromatosis type 1 mutation but a clinical diagnosis of
      Noonan syndrome.

PMID- 22664661
TI  - Is Intelligent Speed Adaptation ready for deployment?
AB  - There have been 30 years of research on Intelligent Speed Adaptation (ISA), the
      in-vehicle system that is designed to promote compliance with speed limits.
      Extensive trials of ISA in real-world driving have shown that ISA can
      significantly reduce speeding, users have been found to have generally positive
      attitudes and at least some sections of the public have been shown to be willing
      to purchase ISA systems. Yet large-scale deployment of a system that could
      deliver huge accident reductions is still by no means guaranteed.

PMID- 22664662
TI  - What benefit does Intelligent Speed Adaptation deliver: a close examination of
      its effect on vehicle speeds.
AB  - Intelligent Speed Adaptation (ISA) is a driver support system which brings the
      speed limit information into the vehicle. This paper describes the UK ISA field
      trials taken place between 2004 and 2006 and presents evidence on how drivers'
      choice of speed is altered. The ISA system was observed to have a distinctive
      effect in transforming the speed distribution from a conventional bell shape to
      an asymmetric distribution biased towards the high speed end. ISA not only
      diminished excessive speeding, but also led to a reduction in speed variation,
      prompting a positive implication to accident reduction. The use of an overridable
      ISA system also provided an opportunity to investigate where drivers would choose
      to have ISA based on observed behaviour instead of opinion. Evidence shows that
      ISA tends to be overridden on roads where it was perhaps needed most. Behavioural
      difference among driver groups also suggests that ISA tends to be overridden by
      those drivers who in safety terms stand to benefit most from using it, as with
      other safety systems.

PMID- 22664663
TI  - Pay as You Speed, ISA with incentives for not speeding: a case of test driver
      recruitment.
AB  - The Intelligent Speed Adaptation (ISA) project we describe in this article is
      based on Pay as You Drive principles. These principles assume that the ISA
      equipment informs a driver of the speed limit, warns the driver when speeding and
      calculates penalty points. Each penalty point entails the reduction of a 30%
      discount on the driver's car insurance premium, which therefore produced the
      name, Pay as You Speed. The ISA equipment consists of a GPS-based On Board Unit
      with a mobile phone connection to a web server. The project was planned for a
      three-year test period with 300 young car drivers, but it never succeeded in
      recruiting that number of drivers. After several design changes, the project
      eventually went forward with 153 test drivers of all ages. This number represents
      approximately one thousandth of all car owners in the proving ground of North
      Jutland in Denmark. Furthermore the project was terminated before its scheduled
      closing date. This article describes the project with an emphasis on recruitment
      efforts and the project's progress. We include a discussion of possible
      explanations for the failure to recruit volunteers for the project and reflect
      upon the general barriers to using ISA with ordinary drivers.

PMID- 22664664
TI  - Pay as You Speed, ISA with incentive for not speeding: results and interpretation
      of speed data.
AB  - To simulate a market introduction of Intelligent Speed Adaptation (ISA) and to
      study the effect of a Pay as You Speed (PAYS) concept, a field trial with 153
      drivers was conducted during 2007-2009. The participants drove under PAYS
      conditions for a shorter or a longer period. The PAYS concept consisted of
      informative ISA linked with economic incentive for not speeding, measured through
      automatic count of penalty points whenever the speed limit was exceeded. The full
      incentive was set to 30% of a participant's insurance premium. The participants
      were exposed to different treatments, with and without incentive crossed with
      informative ISA present or absent. The results showed that ISA is an efficient
      tool for reducing speeding particularly on rural roads. The analysis of speed
      data demonstrated that the proportion of distance driven above the speed where
      the ISA equipment responded (PDA) was a sensitive measure for reflecting the
      effect of ISA, whereas mean free flow speed and the 85th percentile speed, were
      less sensitive to ISA effects. The PDA increased a little over time but still
      remained at a low level; however, when ISA was turned off, the participants'
      speeding relapsed to the baseline level. Both informative ISA and incentive ISA
      reduced the PDA, but there was no statistically significant interaction.
      Informative reduced it more than the incentive.

PMID- 22664665
TI  - Could Intelligent Speed Adaptation make overtaking unsafe?
AB  - This driving simulator study investigated how mandatory and voluntary ISA might
      affect a driver's overtaking decisions on rural roads, by presenting drivers with
      a variety of overtaking scenarios designed to evaluate both the frequency and
      safety of the manoeuvres. In half the overtaking scenarios, ISA was active and in
      the remainder ISA was switched off. A rural road was modelled with a number of
      2+1 road sections, thus allowing drivers a protected overtaking opportunity. The
      results indicate that drivers became less inclined to initiate an overtaking
      manoeuvre when the mandatory ISA was active and this was particularly so when the
      overtaking opportunity was short. In addition to this, when ISA was activated
      drivers were more likely to have to abandon an overtaking, presumably due to
      running out of road. They also spent more time in the critical hatched area-a
      potentially unsafe behaviour. The quality of the overtaking manoeuvre was also
      affected when mandatory ISA was active, with drivers pulling out and cutting back
      in more sharply. In contrast, when driving with a voluntary ISA, overtaking
      behaviour remained mostly unchanged: drivers disengaged the function in
      approximately 70% of overtaking scenarios. The results of this study suggest that
      mandatory ISA could affect the safety of overtaking manoeuvres unless coupled
      with an adaptation period or other driver support functions that support safe
      overtaking.

PMID- 22664666
TI  - Adapting ISA system warnings to enhance user acceptance.
AB  - Inappropriate speed is a major cause of traffic accidents. Different measures
      have been considered to control traffic speed, and intelligent speed adaptation
      (ISA) systems are one of the alternatives. These systems know the speed limits
      and try to improve compliance with them. This paper deals with an informative ISA
      system that provides the driver with an advance warning before reaching a road
      section with singular characteristics that require a lower safe speed than the
      current speed. In spite of the extensive tests performed using ISA systems, few
      works show how warnings can be adapted to the driver. This paper describes a
      method to adapt warning parameters (safe speed on curves, zone of influence of a
      singular stretch, deceleration process and reaction time) to normal driving
      behavior. The method is based on a set of tests with and without the ISA system.
      This adjustment, as well as the analysis of driver acceptance before and after
      the adaptation and changes in driver behavior (changes in speed and path)
      resulting from the tested ISA regarding a driver's normal driving style, is shown
      in this paper. The main conclusion is that acceptance by drivers increased
      significantly after redefining the warning parameters, but the effect of speed
      homogenization was not reduced.

PMID- 22664667
TI  - Can enforced behaviour change attitudes: exploring the influence of Intelligent
      Speed Adaptation.
AB  - The Theory of Planned Behaviour model (Ajzen, 1985) was used to determine whether
      long-term experience with Intelligent Speed Adaption (ISA) prompts a change in
      speed related cognitions. The study examines data collected as part of a project
      examining driver behaviour with an intervening but overridable ISA system. Data
      was collected in four six-month field trials. The trials followed an A-B-A design
      (28 days driving with no ISA, 112 days driving with ISA, 28 days driving without
      ISA) to monitor changes in speeding behaviour as a result of the ISA system and
      any carry-over effect of the system. Findings suggested that following experience
      with the system, drivers' intention to speed significantly weakened, beyond the
      removal of ISA support. Drivers were also less likely to believe that exceeding
      the speed would 'get them to their destination more quickly' and less likely to
      believe that 'being in a hurry' would facilitate speeding. However, the positive
      change in intentions and beliefs failed to translate into behaviour. Experience
      with the ISA system significantly reduced the percentage of distance travelled
      whilst exceeding the speed limit but this effect was not evident when the ISA
      support was removed.

PMID- 22664668
TI  - Intelligent speed adaptation as an assistive device for drivers with acquired
      brain injury: a single-case field experiment.
AB  - Intelligent speed adaptation (ISA) was tested as an assistive device for drivers
      with an acquired brain injury (ABI). The study was part of the "Pay as You Speed"
      project (PAYS) and used the same equipment and technology as the main study
      (Lahrmann et al., in press-a, in press-b). Two drivers with ABI were recruited as
      subjects and had ISA equipment installed in their private vehicle. Their speed
      was logged with ISA equipment for a total of 30 weeks of which 12 weeks were with
      an active ISA user interface (6 weeks=Baseline 1; 12 weeks=ISA period; 12
      weeks=Baseline 2). The subjects participated in two semi-structured interviews
      concerning their strategies for driving with ABI and for driving with ISA.
      Furthermore, they gave consent to have data from their clinical journals and be a
      part of the study. The two subjects did not report any instances of being
      distracted or confused by ISA, and in general they described driving with ISA as
      relaxed. ISA reduced the percentage of the total distance that was driven with a
      speed above the speed limit (PDA), but the subjects relapsed to their previous
      PDA level in Baseline 2. This suggests that ISA is more suited as a permanent
      assistive device (i.e. cognitive prosthesis) than as a temporary training device.
      As ABI is associated with a multitude of cognitive deficits, we developed a
      conceptual framework, which focused on the cognitive parameters that have been
      shown to relate to speeding behaviour, namely "intention to speed" and
      "inattention to speeding". The subjects' combined status on the two independent
      parameters made up their "speeding profile". A comparison of the speeding
      profiles and the speed logs indicated that ISA in the present study was more
      efficient in reducing inattention to speeding than affecting intention to speed.
      This finding suggests that ISA might be more suited for some neuropsychological
      profiles than for others, and that customisation of ISA for different
      neuropsychological profiles may be required. However, further studies with more
      subjects are needed in order to be conclusive on these issues.

PMID- 22664669
TI  - How much benefit does Intelligent Speed Adaptation deliver: an analysis of its
      potential contribution to safety and environment.
AB  - The UK Intelligent Speed Adaptation (ISA) project produced a rich database with
      high-resolution data on driver behaviour covering a comprehensive range of road
      environment. The field trials provided vital information on driver behaviour in
      the presence of ISA. The purpose of this paper is to exploit the information
      gathered in the field trials to predict the impacts of various forms of ISA and
      to assess whether ISA is viable in terms of benefit-to-cost ratio. ISA is
      predicted to save up to 33% of accidents on urban roads, and to reduce CO(2)
      emissions by up to 5.8% on 70 mph roads. In order to investigate the long-term
      impacts of ISA, two hypothetical deployment scenarios were envisaged covering a
      60-year appraisal period. The results indicate that ISA could deliver a very
      healthy benefit-to-cost ratio, ranging from 3.4 to 7.4, depending on the
      deployment scenarios. Under both deployment scenarios, ISA has recovered its
      implementation costs in less than 15 years. It can be concluded that
      implementation of ISA is clearly justified from a social cost and benefit
      perspective. Of the two deployment scenarios, the Market Driven one is
      substantially outperformed by the Authority Driven one. The benefits of ISA on
      fuel saving and emission reduction are real but not substantial, in comparison
      with the benefits on accident reduction; up to 98% of benefits are attributable
      to accident savings. Indeed, ISA is predicted to lead to a savings of 30% in
      fatal crashes and 25% in serious crashes over the 60-year period modelled.

PMID- 22664670
TI  - Deal or no deal: can incentives encourage widespread adoption of intelligent
      speed adaptation devices?
AB  - Given the burden of injury, economic, environmental and social consequences
      associated with speeding, reducing road traffic speed remains a major priority.
      Intelligent speed adaptation (ISA) is a promising but controversial new in
      vehicle system that provides drivers with support on the speed-control task. In
      order to model potential system uptake, this paper explores drivers' preferences
      for two different types of ISA given a number of alternative fiscal incentives
      and non-fiscal measures, using a stated preference approach. As would be expected
      with such a contentious issue, the analysis revealed the presence of significant
      variations in sensitivities and preferences in the sample. While a non-negligible
      part of the sample population has such strong opposition to ISA that no
      reasonable discounts or incentives would lead to them buying or accepting such a
      system, there is also a large part of the population that, if given the right
      incentives, would be willing or even keen to equip their vehicle with an ISA
      device.

PMID- 22664672
TI  - Editorial. Construction and engineering projects.

PMID- 22664671
TI  - ISA implementation and uncertainty: a literature review and expert elicitation
      study.
AB  - Each day, an average of over 116 people die from traffic accidents in the
      European Union. One out of three fatalities is estimated to be the result of
      speeding. The current state of technology makes it possible to make speeding more
      difficult, or even impossible, by placing intelligent speed limiters (so called
      ISA devices) in vehicles. Although the ISA technology has been available for some
      years now, and reducing the number of road traffic fatalities and injuries has
      been high on the European political agenda, implementation still seems to be far
      away. Experts indicate that there are still too many uncertainties surrounding
      ISA implementation, and dealing with these uncertainties is essential for
      implementing ISA. In this paper, a systematic and representative inventory of the
      uncertainties is made based upon the literature. Furthermore, experts in the
      field of ISA were surveyed and asked which uncertainties are barriers for ISA
      implementation, and how uncertain these uncertainties are. We found that the long
      term effects and the effects of large-scale implementation of ISA are still
      uncertain and are the most important barriers for the implementation of the most
      effective types of ISA. One way to deal with these uncertainties would be to
      start implementation on a small scale and gradually expand the penetration, in
      order to learn how ISA influences the transport system over time.

PMID- 22664673
TI  - Error begat error: design error analysis and prevention in social infrastructure
      projects.
AB  - Design errors contribute significantly to cost and schedule growth in social
      infrastructure projects and to engineering failures, which can result in
      accidents and loss of life. Despite considerable research that has addressed
      their error causation in construction projects they still remain prevalent. This
      paper identifies the underlying conditions that contribute to design errors in
      social infrastructure projects (e.g. hospitals, education, law and order type
      buildings). A systemic model of error causation is propagated and subsequently
      used to develop a learning framework for design error prevention. The research
      suggests that a multitude of strategies should be adopted in congruence to
      prevent design errors from occurring and so ensure that safety and project
      performance are ameliorated.

PMID- 22664674
TI  - A systems approach to accident causation in mining: an application of the HFACS
      method.
AB  - This project aimed to provide a greater understanding of the systemic factors
      involved in mining accidents, and to examine those organisational and supervisory
      failures that are predictive of sub-standard performance at operator level. A
      sample of 263 significant mining incidents in Australia across 2007-2008 were
      analysed using the Human Factors Analysis and Classification System (HFACS). Two
      human factors specialists independently undertook the analysis. Incidents
      occurred more frequently in operations concerning the use of surface mobile
      equipment (38%) and working at heights (21%), however injury was more frequently
      associated with electrical operations and vehicles and machinery. Several HFACS
      categories appeared frequently: skill-based errors (64%) and violations (57%),
      issues with the physical environment (56%), and organisational processes (65%).
      Focussing on the overall system, several factors were found to predict the
      presence of failures in other parts of the system, including planned
      inappropriate operations and team resource management; inadequate supervision and
      team resource management; and organisational climate and inadequate supervision.
      It is recommended that these associations deserve greater attention in future
      attempts to develop accident countermeasures, although other significant
      associations should not be ignored. In accordance with findings from previous
      HFACS-based analyses of aviation and medical incidents, efforts to reduce the
      frequency of unsafe acts or operations should be directed to a few critical HFACS
      categories at the higher levels: organisational climate, planned inadequate
      operations, and inadequate supervision. While remedial strategies are proposed it
      is important that future efforts evaluate the utility of the measures proposed in
      studies of system safety.

PMID- 22664675
TI  - Dynamics of safety performance and culture: a group model building approach.
AB  - The management of occupational health and safety (OHS) including safety culture
      interventions is comprised of complex problems that are often hard to scope and
      define. Due to the dynamic nature and complexity of OHS management, the concept
      of system dynamics (SD) is used to analyze accident prevention. In this paper, a
      system dynamics group model building (GMB) approach is used to create a causal
      loop diagram of the underlying factors influencing the OHS performance of a major
      drilling and mining contractor in Australia. While the organization has invested
      considerable resources into OHS their disabling injury frequency rate (DIFR) has
      not been decreasing. With this in mind, rich individualistic knowledge about the
      dynamics influencing the DIFR was acquired from experienced employees with
      operations, health and safety and training background using a GMB workshop.
      Findings derived from the workshop were used to develop a series of causal loop
      diagrams that includes a wide range of dynamics that can assist in better
      understanding the causal influences OHS performance. The causal loop diagram
      provides a tool for organizations to hypothesize the dynamics influencing
      effectiveness of OHS management, particularly the impact on DIFR. In addition the
      paper demonstrates that the SD GMB approach has significant potential in
      understanding and improving OHS management.

PMID- 22664676
TI  - Investigating the multi-causal and complex nature of the accident causal
      influence of construction project features.
AB  - Construction project features (CPFs) are organisational, physical and operational
      attributes that characterise construction projects. Although previous studies
      have examined the accident causal influence of CPFs, the multi-causal attribute
      of this causal phenomenon still remain elusive and thus requires further
      investigation. Aiming to shed light on this facet of the accident causal
      phenomenon of CPFs, this study examines relevant literature and crystallises the
      attained insight of the multi-causal attribute by a graphical model which is
      subsequently operationalised by a derived mathematical risk expression that
      offers a systematic approach for evaluating the potential of CPFs to cause harm
      and consequently their health and safety (H&S) risk implications. The graphical
      model and the risk expression put forth by the study thus advance current
      understanding of the accident causal phenomenon of CPFs and they present an
      opportunity for project participants to manage the H&S risk associated with CPFs
      from the early stages of project procurement.

PMID- 22664677
TI  - Relational approach in managing construction project safety: a social capital
      perspective.
AB  - Existing initiatives in the management of construction project safety are largely
      based on normative compliance and error prevention, a risk management approach.
      Although advantageous, these approaches are not wholly successful in further
      lowering accident rates. A major limitation lies with the approaches' lack of
      emphasis on the social and team processes inherent in construction project
      settings. We advance the enquiry by invoking the concept of social capital and
      project organisational processes, and their impacts on project safety
      performance. Because social capital is a primordial concept and affects project
      participants' interactions, its impact on project safety performance is
      hypothesised to be indirect, i.e. the impact of social capital on safety
      performance is mediated by organisational processes in adaptation and
      cooperation. A questionnaire survey was conducted within Hong Kong construction
      industry to test the hypotheses. 376 usable responses were received and used for
      analyses. The results reveal that, while the structural dimension is not
      significant, the mediational thesis is generally supported with the cognitive and
      relational dimensions affecting project participants' adaptation and cooperation,
      and the latter two processes affect safety performance. However, the cognitive
      dimension also directly affects safety performance. The implications of these
      results for project safety management are discussed.

PMID- 22664678
TI  - Potential difficulties in applying the Pay for Safety Scheme (PFSS) in
      construction projects.
AB  - Since 1996, the Government of the Hong Kong Special Administrative Region (HKSAR)
      has introduced the Pay for Safety Scheme (PFSS) to the public works construction
      contracts to uplift their safety performance. However, the adoption of PFSS has
      also encountered some difficulties that merit considerable attention. This paper
      purports to provide a concise review of the prevailing application of PFSS in
      Hong Kong in general, and to explore the potential difficulties associated with
      PFSS in particular. By means of an empirical questionnaire survey geared towards
      industrial practitioners with extensive direct hands-on PFSS experience, their
      opinions were solicited, analyzed and compared between the client group and
      contractor group of respondents. The three most significant difficulties in
      implementing PFSS were found to be: (1) "Plenty of paperwork required for
      certifying payment to contractor"; (2) "Complicated contract documents and
      lengthy assessment process"; and (3) "Over-tight project schedule requiring rush
      jobs". The output of this research study is particularly essential in assisting
      the contracting parties to mitigate the avoidable hindrances when embarking on
      PFSS. It has also generated valuable insights into developing effective
      recommendations for alleviating the barriers to PFSS success for future
      construction projects.

PMID- 22664679
TI  - Preventing construction worker injury incidents through the management of
      personal stress and organizational stressors.
AB  - Construction workers (CWs) are positioned at the lowest level of an organization
      and thus have limited control over their work. For this reason, they are often
      deprived of their due rewards and training or sometimes are even compelled to
      focus on production at the expense of their own safety. These organizational
      stressors not only cause the CWs stress but also impair their safety behaviors.
      The impairment of safety behaviors is the major cause of CW injury incidents.
      Hence, to prevent injury incidents and enhance safety behaviors of CWs, the
      current study aimed to identify the impact of various organizational stressors
      and stress on CW safety behaviors and injury incidents. To achieve this aim, we
      surveyed 395 CWs. Using factor analysis, we identified five organizational
      stressors (unfair reward and treatment, inappropriate safety equipment, provision
      of training, lack of goal setting, and poor physical environment), two types of
      stress (emotional and physical), and safety behaviors. The results of correlation
      and regression analyses revealed the following: (1) injury incidents were
      minimized by safety behaviors but escalated by a lack of goal setting, (2) safety
      behaviors were maximized by moderate levels of emotional stress (i.e., an
      inverted U-shape relationship between these two variables) and increased in line
      with physical stress and inappropriate safety equipment, (3) emotional stress was
      positively predicted by the provision of training and inappropriate safety
      equipment, and (4) physical stress was predicted only by inappropriate safety
      equipment. Based on these results, we suggest various recommendations to
      construction stakeholders on how to prevent CW injury incidents.

PMID- 22664680
TI  - Towards a better reliability of risk assessment: development of a qualitative &
      quantitative risk evaluation model (Q2REM) for different trades of construction
      works in Hong Kong.
AB  - Since the safety professionals are the key decision makers dealing with project
      safety and risk assessment in the construction industry, their perceptions of
      safety risk would directly affect the reliability of risk assessment. The safety
      professionals generally tend to heavily rely on their own past experiences to
      make subjective decisions on risk assessment without systematic decision making.
      Indeed, understanding of the underlying principles of risk assessment is
      significant. In this study, the qualitative analysis on the safety professionals'
      beliefs of risk assessment and their perceptions towards risk assessment,
      including their recognitions of possible accident causes, the degree of
      differentiations on their perceptions of risk levels of different trades of
      works, recognitions of the occurrence of different types of accidents, and their
      inter-relationships with safety performance in terms of accident rates will be
      explored in the Stage 1. At the second stage, the deficiencies of the current
      general practice for risk assessment can be sorted out firstly. Based on the
      findings from Stage 1 and the historical accident data from 15 large-scaled
      construction projects in 3-year average, a risk evaluation model prioritizing the
      risk levels of different trades of works and which cause different types of site
      accident due to various accident causes will be developed quantitatively. With
      the suggested systematic accident recording techniques, this model can be
      implemented in the construction industry at both project level and organizational
      level. The model (Q(2)REM) not only act as a useful supplementary guideline of
      risk assessment for the construction safety professionals, but also assists them
      to pinpoint the potential risks on site for the construction workers under
      respective trades of works through safety trainings and education. It, in turn,
      arouses their awareness on safety risk. As the Q(2)REM can clearly show the
      potential accident causes leading to different types of accident by trade of
      works, it helps the concerned safety professionals and parties to plan effective
      accident prevention measures with reference to the priority of the risk levels.

PMID- 22664681
TI  - A suggested color scheme for reducing perception-related accidents on
      construction work sites.
AB  - Changes in workforce demographics have led to the need for more sophisticated
      approaches to addressing the safety requirements of the construction industry.
      Despite extensive research in other industry domains, the construction industry
      has been passive in exploring the impact of a color scheme; perception-related
      accidents have been effectively diminished by its implementation. The research
      demonstrated that the use of appropriate color schemes could improve the actions
      and psychology of workers on site, thereby increasing their perceptions of
      potentially dangerous situations. As a preliminary study, the objects selected by
      rigorous analysis on accident reports were workwear, safety net, gondola,
      scaffolding, and safety passage. The colors modified on site for temporary
      facilities were adopted from existing theoretical and empirical research that
      suggests the use of certain colors and their combinations to improve visibility
      and conspicuity while minimizing work fatigue. The color schemes were also tested
      and confirmed through two workshops with workers and managers currently involved
      in actual projects. The impacts of color schemes suggested in this paper are
      summarized as follows. First, the color schemes improve the conspicuity of
      facilities with other on site components, enabling workers to quickly discern and
      orient themselves in their work environment. Secondly, the color schemes have
      been selected to minimize the visual work fatigue and monotony that can
      potentially increase accidents.

PMID- 22664682
TI  - Design and implementation of an identification system in construction site safety
      for proactive accident prevention.
AB  - Identifying accident precursors using real-time identity information has great
      potential to improve safety performance in construction industry, which is still
      suffering from day to day records of accident fatality and injury. Based on the
      requirements analysis for identifying precursor and the discussion of enabling
      technology solutions for acquiring and sharing real-time automatic identification
      information on construction site, this paper proposes an identification system
      design for proactive accident prevention to improve construction site safety.
      Firstly, a case study is conducted to analyze the automatic identification
      requirements for identifying accident precursors in construction site. Results
      show that it mainly consists of three aspects, namely access control, training
      and inspection information and operation authority. The system is then designed
      to fulfill these requirements based on ZigBee enabled wireless sensor network
      (WSN), radio frequency identification (RFID) technology and an integrated ZigBee
      RFID sensor network structure. At the same time, an information database is also
      designed and implemented, which includes 15 tables, 54 queries and several
      reports and forms. In the end, a demonstration system based on the proposed
      system design is developed as a proof of concept prototype. The contributions of
      this study include the requirement analysis and technical design of a real-time
      identity information tracking solution for proactive accident prevention on
      construction sites. The technical solution proposed in this paper has a
      significant importance in improving safety performance on construction sites.
      Moreover, this study can serve as a reference design for future system
      integrations where more functions, such as environment monitoring and location
      tracking, can be added.

PMID- 22664683
TI  - Using game technologies to improve the safety of construction plant operations.
AB  - Many accidents occur world-wide in the use of construction plant and equipment,
      and safety training is considered by many to be one of the best approaches to
      their prevention. However, current safety training methods/tools are unable to
      provide trainees with the hands-on practice needed. Game technology-based safety
      training platforms have the potential to overcome this problem in a virtual
      environment. One such platform is described in this paper - its characteristics
      are analysed and its possible contribution to safety training identified. This is
      developed and tested by means of a case study involving three major pieces of
      construction plant, which successfully demonstrates that the platform can improve
      the process and performance of the safety training involved in their operation.
      This research not only presents a new and useful solution to the safety training
      of construction operations, but illustrates the potential use of advanced
      technologies in solving construction industry problems in general.

PMID- 22664684
TI  - Applying data mining techniques to explore factors contributing to occupational
      injuries in Taiwan's construction industry.
AB  - Construction accident research involves the systematic sorting, classification,
      and encoding of comprehensive databases of injuries and fatalities. The present
      study explores the causes and distribution of occupational accidents in the
      Taiwan construction industry by analyzing such a database using the data mining
      method known as classification and regression tree (CART). Utilizing a database
      of 1542 accident cases during the period 2000-2009, the study seeks to establish
      potential cause-and-effect relationships regarding serious occupational accidents
      in the industry. The results of this study show that the occurrence rules for
      falls and collapses in both public and private project construction industries
      serve as key factors to predict the occurrence of occupational injuries. The
      results of the study provide a framework for improving the safety practices and
      training programs that are essential to protecting construction workers from
      occasional or unexpected accidents.

PMID- 22664685
TI  - Proposal of a risk-factor-based analytical approach for integrating occupational
      health and safety into project risk evaluation.
AB  - Excluding occupational health and safety (OHS) from project management is no
      longer acceptable. Numerous industrial accidents have exposed the ineffectiveness
      of conventional risk evaluation methods as well as negligence of risk factors
      having major impact on the health and safety of workers and nearby residents.
      Lack of reliable and complete evaluations from the beginning of a project
      generates bad decisions that could end up threatening the very existence of an
      organization. This article supports a systematic approach to the evaluation of
      OHS risks and proposes a new procedure based on the number of risk factors
      identified and their relative significance. A new concept called risk factor
      concentration along with weighting of risk factor categories as contributors to
      undesirable events are used in the analytical hierarchy process multi-criteria
      comparison model with Expert Choice((c)) software. A case study is used to
      illustrate the various steps of the risk evaluation approach and the quick and
      simple integration of OHS at an early stage of a project. The approach allows
      continual reassessment of criteria over the course of the project or when new
      data are acquired. It was thus possible to differentiate the OHS risks from the
      risk of drop in quality in the case of the factory expansion project.

PMID- 22664686
TI  - Rapid demountable platform (RDP)--a device for preventing fall from height
      accidents.
AB  - The prevention of fall from height accidents has long been a popular topic in the
      field of construction safety. Previous research has indicated one of the
      potential hazards was induced by the use of steel bracket as scaffold support.
      While researchers are focusing to improve the existing scaffolding system, this
      research introduces a newly developed device to minimize fall accidents. The
      working platform, namely Rapid Demountable Platform (RDP) can be applied across
      window frames without fixing anchor bolts. Emphasizing on the rapid
      installation/dismantling, the RDP provides another safer option for working at
      height. The development of the RDP has incorporated modular concept and aesthetic
      factor into the design, achieving a more user-friendly platform. Although the RDP
      is not intended to totally replace the traditional bamboo truss-out scaffold, it
      is designed to act as an alternative or a supplement to the existing bamboo truss
      out scaffold. The RDP is the first of this kind to minimize fall from height
      accidents especially in cities similar to Hong Kong where external working at
      height is frequently encountered.

PMID- 22664687
TI  - Valuation of morbidity and mortality risk reductions. Does context matter?
AB  - The main research purpose of the present study was to test for any differences in
      the valuation of morbidity and mortality risk reductions across two contexts;
      traffic and health. A contingent valuation study on preferences for morbidity and
      mortality risk was carried out in Denmark in 2007. Respondents were randomised
      into two different arms: one arm in which the valuation took place in the context
      of health and another arm in which the context was traffic. In both contexts, the
      inferior health state was described by way of the standardized EQ-5D descriptive
      system. We obtained a total sample of 520 respondents from an online database. In
      the present study we found clear evidence of a context effect on expressed
      valuations of identical risk reductions. This was true irrespective of whether
      the adverse outcome in question was death or inferior health. This result
      suggests that interventions targeting risks of death or risks of ill health
      should not necessarily be valued equally across sectors. From a welfare economic
      perspective, the use of the same estimates across contexts - and especially
      across sectors - could be misleading and in worst case lead to inefficient
      resource allocations.

PMID- 22664688
TI  - Estimation of rear-end vehicle crash frequencies in urban road tunnels.
AB  - According to The Handbook of Tunnel Fire Safety, over 90% (55 out of 61 cases) of
      fires in road tunnels are caused by vehicle crashes (especially rear-end
      crashes). It is thus important to develop a proper methodology that is able to
      estimate the rear-end vehicle crash frequency in road tunnels. In this paper, we
      first analyze the time to collision (TTC) data collected from two road tunnels of
      Singapore and conclude that Inverse Gaussian distribution is the best-fitted
      distribution to the TTC data. An Inverse Gaussian regression model is hence used
      to establish the relationship between the TTC and its contributing factors. We
      then proceed to introduce a new concept of exposure to traffic conflicts as the
      mean sojourn time in a given time period that vehicles are exposed to dangerous
      scenarios, namely, the TTC is lower than a predetermined threshold value. We
      further establish the relationship between the proposed exposure to traffic
      conflicts and crash count by using negative binomial regression models. Based on
      the limited data samples used in this study, the negative binomial regression
      models perform well although a further study using more data is needed.

PMID- 22664689
TI  - Drink-driving in community sports clubs: adopting the Good Sports alcohol
      management program.
AB  - Throughout the developed world, community sports clubs are a high-risk setting
      for alcohol-impaired driving. The Good Sports program accredits community sports
      clubs to encourage implementation of alcohol-focussed harm-reduction and safe
      transport strategies. This study tested for associations between participation in
      the Good Sports program and reduced rates of drink-driving amongst club members.
      Multilevel modelling indicated that for each season a club was in the program
      there was an 8% reduction in the odds of drink-driving. These findings may arise
      due to clubs with lower rates of alcohol use maintaining longer involvement in
      the program. However, the findings are also compatible with the intention of the
      Good Sports program to reduce the risk that club members will drive whilst
      alcohol impaired.

PMID- 22664690
TI  - The influence of music on mental effort and driving performance.
AB  - The current research examined the influence of loud music on driving performance,
      and whether mental effort mediated this effect. Participants (N=69) drove in a
      driving simulator either with or without listening to music. In order to test
      whether music would have similar effects on driving performance in different
      situations, we manipulated the simulated traffic environment such that the
      driving context consisted of both complex and monotonous driving situations. In
      addition, we systematically kept track of drivers' mental load by making the
      participants verbally report their mental effort at certain moments while
      driving. We found that listening to music increased mental effort while driving,
      irrespective of the driving situation being complex or monotonous, providing
      support to the general assumption that music can be a distracting auditory
      stimulus while driving. However, drivers who listened to music performed as well
      as the drivers who did not listen to music, indicating that music did not impair
      their driving performance. Importantly, the increases in mental effort while
      listening to music pointed out that drivers try to regulate their mental effort
      as a cognitive compensatory strategy to deal with task demands. Interestingly, we
      observed significant improvements in driving performance in two of the driving
      situations. It seems like mental effort might mediate the effect of music on
      driving performance in situations requiring sustained attention. Other process
      variables, such as arousal and boredom, should also be incorporated to study
      designs in order to reveal more on the nature of how music affects driving.

PMID- 22664691
TI  - Stuck in the 70s: the role of social norms in distracted driving.
AB  - Successful campaigns to end distracted driving must understand prevailing social
      norms for behaviors such as texting and phoning while driving. The current work
      examined this issue by asking younger drivers to read car crash scenarios and
      rate the responsibility of the driver for the crash, and to levy fines and assign
      jail time, as a function of whether the driver was attentive, had been drinking,
      or was distracted by phoning or texting. In the first experiment, ratings were
      performed in the absence of injunctive norm information (laws against drunk and
      distracted driving). In the second experiment, injunctive norm information was
      included. Impaired drivers were viewed as more responsible in both experiments,
      with texting drivers viewed as the most responsible. However, drunk drivers
      received the most fines and jail time. When compared to data from the 1970s, the
      results show that anti-drunk driving campaigns have changed how younger drivers
      view drunk driving, but that norms have not yet changed for distracted driving,
      despite consistent results showing they know the risk of driving distracted.
      Implications for social norm distracted driving campaigns are discussed.

PMID- 22664692
TI  - Hybrid III anthropomorphic test device (ATD) response to head impacts and
      potential implications for athletic headgear testing.
AB  - The Hybrid III 50th percentile male anthropomorphic test device (ATD) is the most
      widely used human impact testing surrogate and has historically been used in
      automotive or military testing. More recently, this ATD is finding use in
      applications evaluating athletic helmet protectivity, quantifying head impact
      dosage and estimating injury risk. But ATD head-neck response has not been
      quantified in omnidirectional athletic-type head impacts absent axial preload. It
      is probable that headgear injury reduction that can be quantified in a
      laboratory, including in American football, boxing, hockey, lacrosse and soccer,
      is related to a number of interrelated kinetic and kinematic factors, such as
      head center of gravity linear acceleration, head angular acceleration, head
      angular velocity, occipito-cervical mechanics and neck stiffness. Therefore, we
      characterized ATD head-neck dynamic response to direct head impacts in a series
      of front, oblique front and lateral head impacts. Key findings were: (1) impacts
      producing highest ATD resultant center of gravity linear acceleration resulted in
      the lowest resultant occipito-cervical spine bending moment/force. (2) Resultant
      ATD head angular velocity and angular acceleration did not appear coupled to
      impact direction at lower impact energy levels; these parameters were coupled at
      higher energy levels. (3) The ATD had progressively increasing occipito-cervical
      stiffness in extension, torsion and lateral bending, respectively. Because the
      ATD neck influenced head and neck impact dosage parameters, testing agencies,
      manufacturers and researchers should consider using the Hybrid III head form
      attached to a neck as a means to quantify head and neck injury risks as opposed
      to systems that do not utilize a neck. This heightened understanding of Hybrid
      III ATD head-neck response, and consideration of order of stiffest axes in the
      lateral, oblique and extension directions, respectively, should aid in the
      development of head and neck injury impact testing standards.

PMID- 22664693
TI  - Self reported risk taking and risk compensation in skiers and snowboarders are
      associated with sensation seeking.
AB  - In alpine skiing, a controversial discussion has been taking place regarding the
      potential influence of wearing a ski helmet on the individual level of risk
      taking behaviour. The aim of this study was to evaluate whether self reported
      risk taking behaviour and self reported risk compensation are associated with the
      personality trait sensation seeking (SS) in alpine skiing and snowboarding. In
      total, 683 persons (36% males and 64% females) completed an online-survey about
      attitudes and use of protective gear in winter sports including the German
      version of the sensation seeking scale form V. A logistic regression analysis
      including gender, age, nationality, preferred winter sport, self reported skiing
      ability, mean skiing time per season, use of ski helmets, and SS total score was
      used to estimated adjusted odds ratios (ORs) and their 95% confidence intervals
      (95 CI) for self reported risk taking behaviour. Regression analysis revealed
      that a more risky behaviour increased with male gender (OR: 2.7), with an age<25
      years (OR: 1.6), with skiing (OR: 1.3), higher skill level (OR: 5.7), and a mean
      skiing time>28 days per season (OR: 2.2). In addition, SS total score was
      significantly higher in more risky compared to more cautious people (23.8 vs.
      20.3, p<.001). Ski helmet use was not found to be predictive for a more risky
      behaviour (p>.05). Also, skiers and snowboarders with self reported risk
      compensation while wearing a ski helmet had higher SS total scores compared to
      those who did not report risk compensation (23.8 vs. 20.9, p=.001). In addition,
      self reported risk compensation in helmet wearers increased with an age<25 years
      (OR: 2.2), a higher skill level (OR: 2.5) and a mean skiing time>28 days per
      season (OR: 2.1). In conclusion, self reported risk taking and self reported risk
      compensation are associated with higher sensation seeking total scores. The
      personality trait sensation seeking, not wearing of a ski helmet, appears to be
      associated with riskier behaviour on the ski slopes.

PMID- 22664694
TI  - Trends in alcohol-impaired driving in Canada.
AB  - While a general decreasing trend in the number of persons killed in a traffic
      crash involving a drinking driver has occurred in Canada since the 1980s, it is
      evident that much of this decrease occurred in the 1990s. Since 2002, less
      progress has been made as the number of persons killed in crashes involving
      drinking drivers remains high. To better understand the current situation, this
      paper describes trends in drinking and driving in Canada from 1998 to 2011 using
      multiple indicators based on data collected for the Traffic Injury Research
      Foundation's (TIRF) Road Safety Monitor (RSM), the National Opinion Poll on
      Drinking and Driving, and trends in alcohol-related crashes based on data
      collected for TIRF's national Fatality Database in Canada. There has been a
      continued and consistent decrease in the number of fatalities involving a
      drinking driver in Canada. This remains true when looking at the number of
      fatalities involving a drinking driver per 100,000 population and per 100,000
      licensed drivers. This decreasing trend is also still apparent when considering
      the percentage of persons killed in a traffic crash in Canada involving a
      drinking driver although less pronounced. Data from the RSM further show that the
      percentage of those who reported driving after they thought they were over the
      legal limit has also declined. However, regardless of the apparent decreasing
      trend in drinking driving fatalities and behaviour, reductions have been
      relatively modest, and fatalities in crashes involving drivers who have consumed
      alcohol remain high at unacceptable levels.

PMID- 22664695
TI  - Recursive modeling of loss of control in human and organizational processes: a
      systemic model for accident analysis.
AB  - A recursive model of accident investigation is proposed by exploiting earlier
      work in systems thinking. Safety analysts can understand better the underlying
      causes of decision or action flaws by probing into the patterns of breakdown in
      the organization of safety. For this deeper analysis, a cybernetic model of
      organizational factors and a control model of human processes have been
      integrated in this article (i.e., the viable system model and the extended
      control model). The joint VSM-ECOM framework has been applied to a case study to
      help safety practitioners with the analysis of patterns of breakdown with regard
      to how operators and organizations manage goal conflicts, monitor work progress,
      recognize weak signals, align goals across teams, and adapt plans on the fly. The
      recursive accident representation brings together several organizational issues
      (e.g., the dilemma of autonomy versus compliance, or the interaction between
      structure and strategy) and addresses how operators adapt to challenges in their
      environment by adjusting their modes of functioning and recovery. Finally, it
      facilitates the transfer of knowledge from diverse incidents and near misses
      within similar domains of practice.

PMID- 22664696
TI  - Safety effects of wider edge lines on rural, two-lane highways.
AB  - Although it is generally expected that wider lines will have a positive effect on
      vehicle safety, there have not been any convincing evidence based on the crash
      data analysis, partly because of the lack of relevant data. In this paper, the
      safety effect of wider edge lines was examined by analyzing crash frequency data
      for road segments with and without wider edge lines. The data from three states,
      Kansas, Michigan, and Illinois, have been analyzed. Because of different nature
      of data from each state, a different statistical analysis approach was employed
      for each state: an empirical Bayes, before-after analysis of Kansas data, an
      interrupted time series design and generalized linear segmented regression
      analysis of Michigan data, and a cross sectional analysis of Illinois data.
      Although it is well-known that causation is hard to establish based on
      observational studies, the results from three extensive statistical analyses all
      point to the same findings. The consistent findings lend support to the positive
      safety effects of wider edge lines installed on rural, two-lane highways.

PMID- 22664697
TI  - The role of sensation seeking, perceived peer pressure, and harmful alcohol use
      in riding with an alcohol-impaired driver.
AB  - Alcohol-related motor vehicle collisions have been the top of policy agenda for
      more than three decades in Korea. Despite implementation of various traffic
      safety measures, some drivers' alcohol use and abuse has resulted in a high
      number of alcohol-impaired traffic fatalities every year. This paper presents the
      association of theoretical factors with behavior of riding with an alcohol
      impaired driver (RAID) among all age groups in the Korean adult sample. The
      theoretical factors of the drivers are personality factor, socio-psychological
      factor, and alcohol-related behavioral risk factor. We utilized national survey
      data from 1007 respondents consisting of 703 males and 304 females aged 20-66
      collected by Korean Institute of Criminology (KIC) to test our theorized model.
      Our results indicated that there were three major predictors of RAID involvement:
      sensation seeking propensity, perceived peer pressure, and frequent harmful
      drinking. Overall, prediction of RAID behavior by gender was mediated entirely
      through these predictors. The issue of males' higher risk of RAID involvements
      was addressed for effective communication strategies such as campaigns.

PMID- 22664698
TI  - Motorcycle and scooter speeds approaching urban intersections.
AB  - Five urban, uncontrolled T-intersections known to be motorcycle crash 'black
      spots' were monitored using instrumentation and a roadside observer. Two sets of
      twelve-hour observations were collected for each site (N~100,000).
      Instrumentation recorded the 'events' of vehicles passing to measure, speed,
      direction, lane position, vehicle type (broadly characterised) and headway.
      Observers further recorded times of bicycle events, type of motorcycle (scooters
      or motorcycles), the behaviour of motorcycles and the use of 'high conspicuity'
      gear such as clothing or helmets. Results establish that motorcycles travel
      around 10% faster than the other traffic (car mean speed=34.97 km/h), with
      motorcycles travelling on average 3.3 km/h faster than cars. Motorcycles were 3.4
      times more likely to be exceeding the speed limit than cars. Similar results are
      described for scooters. Also examined are the influences on mean speeds such as
      the time of day, the presence of a car at the t-intersection, and the influence
      of free headway. The results are compared for robustness across locations and
      days. It is concluded that in urban areas motorcycles are travelling
      significantly faster than other traffic. These findings are discussed against a
      concern to reduce motorcycle crashes by improving conspicuity and previous
      research that implicates a 'looked-but-failed-to-see' effect for car drivers.

PMID- 22664699
TI  - Judgments of approach speed for motorcycles across different lighting levels and
      the effect of an improved tri-headlight configuration.
AB  - The misperception of vehicle approach speed is a key contributory factor to road
      traffic crash involvement. Past research has indicated that individuals use the
      rate of visual looming to calculate the time to passage (TTP) of a vehicle, and
      that smaller vehicles loom to a lesser extent than larger vehicles. Despite a
      disproportionate number of fatal injuries occurring on the road after dark, and a
      higher than average number of accidents involving automobile drivers violating
      the right of way of a motorcyclist occurring in low light conditions, there has
      been very little consideration of the accuracy of TTP for smaller and larger
      vehicles under low levels of luminance. We investigated drivers' judgments of
      motorcycle and car approach speeds across a number of levels of luminance within
      a virtual city scene, as well as the effectiveness of a tri-headlight formation
      on motorcycle speed judgments. The accuracy of car approach speed judgments were
      not affected by changes in lighting conditions, but speed judgments for the solo
      headlight motorcycle became significantly less accurate as lighting reduced in
      the early night and night-time conditions. Incorporation of a tri-headlight
      formation onto the standard motorcycle frame resulted in improved accuracy of
      approach speed judgments, relative to the solo headlight motorcycle, as ambient
      light levels reduced. The practical implications of the findings are discussed in
      terms of road safety and motorcycle design.

PMID- 22664700
TI  - Safety effects of low-cost engineering measures. An observational study in a
      Portuguese multilane road.
AB  - Single carriageway multilane roads are not, in general, a very safe type of road,
      mainly because of the high number of seriously injured victims in head-on
      collisions, when compared with dual carriageway multilane roads, with a median
      barrier. In this paper the results of a study on the effect of the application of
      several low cost engineering measures, aimed at road infrastructure correction
      and road safety improvement on a multilane road (EN6), are presented. The study
      was developed by the National Laboratory of Civil Engineering (LNEC) for the
      Portuguese Road Administration and involved a comparison of selected aspects of
      motorized traffic behaviour (traffic volumes and speeds) measured in several
      sections of EN6, as well as monitoring of road safety developments in the same
      road. The applied low cost engineering measures allowed a reduction of 10% in the
      expected annual number of personal injury accidents and a 70% decrease in the
      expected annual number of head-on collisions; the expected annual frequency of
      accidents involving killed and seriously injured persons was reduced by 26%.

PMID- 22664701
TI  - Population behavioral scenarios influencing radiological disaster preparedness
      and planning.
AB  - Considerable attention is focused on plans for sheltering or evacuating the
      population of the US national capital region in response to a regional emergency
      such as a terrorist attack or natural disaster. Such planning engages multiple
      disciplines spanning infrastructure engineering, emergency management, health
      care, mass communication, water and food supply, logistics, and others. Knowledge
      of population behaviors should influence the many dimensions of protection,
      prevention, response, and recovery. Of particular interest are the behaviors and
      needs of the resident and non-resident populations in the aftermath of a regional
      disaster, including those at home, at work, and traveling. The authors deployed a
      30-min telephone survey to 2700 residents of the region to gain knowledge of
      their intended behaviors in the event of a variety of potential dirty bomb
      attacks. The survey provides a unique foundation for the current paper. The paper
      will identify and model the assumptions of population behaviors that most affect
      agency priorities for emergency planning including regional sheltering and
      evacuation following a radiological disaster such as a dirty bomb. The technical
      approach assessed several planning initiatives across performance criteria
      derived from strategic plans and applied combinations of behavioral assumptions
      to vary the relative importance of each criterion. The results reveal the
      behavioral scenarios that are most significant to the prioritization of planning
      initiatives and identify the highest and lowest priority initiatives across the
      criteria used.

PMID- 22664702
TI  - Effect of North Carolina's restriction on teenage driver cell phone use two years
      after implementation.
AB  - A majority of states now restrict teenagers from using a mobile communication
      device while driving. The effect of these restrictions is largely unknown. In a
      previous study, we found North Carolina's teenage driver cell phone restriction
      had little influence on young driver behavior four months after the law took
      effect (Foss et al., 2009). The goal of the present study was to examine the
      longer-term effect of North Carolina's cell phone restriction. It was expected
      that compliance with the restriction would increase, as awareness of the
      restriction grew over time. Teenagers were observed at high schools in North
      Carolina approximately two years after the law was implemented. Observations were
      also conducted in South Carolina, which did not have a cell phone restriction. In
      both states, there was a broad decrease in cell phone use. A logistic regression
      analysis showed the decrease in cell phone use did not significantly differ
      between the two states. Although hand-held cell phone use decreased, there was an
      increase in the likelihood that drivers in North Carolina were observed
      physically manipulating a phone. Finally, a mail survey of teenagers in North
      Carolina showed awareness for the cell phone restriction now stands at 78% among
      licensed teens. Overall, the findings suggest North Carolina's cell phone
      restriction has had no long-term effect on the behavior of teenage drivers.
      Moreover, it appears many teenage drivers may be shifting from talking on a phone
      to texting.

PMID- 22664703
TI  - A disaggregate model for quantifying the safety effects of winter road
      maintenance activities at an operational level.
AB  - This research presents a disaggregated modeling approach for investigating the
      link between winter road collision occurrence, weather, road surface conditions,
      traffic exposure, temporal trends and site-specific effects. This approach is
      unique as it allows for quantification of the safety effects of different winter
      road maintenance activities at an operational level. Different collision
      frequency models are calibrated using hourly data collected from 31 different
      highway routes across Ontario, Canada. It is found that factors such as
      visibility, precipitation intensity, air temperature, wind speed, exposure, month
      of the winter season, and storm hour have statistically significant effects on
      winter road safety. Most importantly, road surface conditions are identified as
      one of the major contributing factors, representing the first contribution
      showing the empirical relationship between safety and road surface conditions at
      such a disaggregate level. The applicability of the modeling framework is
      demonstrated using several examples, such as quantification of the benefits of
      alternative maintenance operations and evaluation of the effects of different
      service standards using safety as a performance measure.

PMID- 22664704
TI  - Investigating the factorial invariance of the 28-item DBQ across genders and age
      groups: an Exploratory Structural Equation Modeling study.
AB  - The Driver Behaviour Questionnaire (DBQ) is perhaps the most widely used
      questionnaire instrument in traffic psychology with 174 studies published by late
      2010. The instrument was developed based on a plausible cognitive ergonomic
      theory (the Generic Error Modeling System, GEMS), but the factor structure
      obtained in the original study (Reason et al., 1990) did not mirror the theory's
      conceptual structure. This led to abandoning GEMS and adopting the obtained
      factor structure as a starting point for further DBQ research. This article
      argues that (1) certain choices in the original study, concerning statistical
      methodology and the wording of individual question items, may have contributed to
      the ways the obtained factor structure deviated from the underlying theory and
      (2) the analysis methods often used in DBQ studies, principal components (PC)
      analysis and maximum likelihood (ML) factor analysis, are not optimal choices for
      the non-normally distributed categorical data that is obtained using the
      instrument. This is because ML produces biased results when used with this type
      of data, while PC is by definition unable to uncover latent factors as it
      summarizes all variation in the measured variables. (3) Even though DBQ factor
      scores have been routinely compared in subgroups of men and women and respondents
      of different ages, DBQ's factorial invariance in these groups has not been
      rigorously tested. These concerns are addressed in this article by framing the
      results of certain previous DBQ studies as a structural equation model (SEM) and
      an Exploratory Structural Equation Model (ESEM) and testing measurement model fit
      in subgroups of respondents. The SEM analyses indicate that the model does not
      fit data from the whole sample of respondents as it stands, while the ESEM
      analyses show that a modification of the model does. However, the ESEM analyses
      indicate the DBQ measures different underlying latent variables in the different
      subgroups. Based on the analyses and a review of recent advances in attention and
      memory research, an update to the theory underlying the DBQ is suggested.

PMID- 22664705
TI  - ER visits predict premature death among teenagers.
AB  - BACKGROUND: The purpose of this study was to investigate if teenagers visiting an
      emergency room because of injury have an increased risk of premature death ahead
      and, if so, identify possible risk factors and suggest preventive measures.
      METHODS: In January 2010, the personal identity numbers of 12,812 teenagers who
      had visited the emergency room at the University Hospital in Umea, Sweden, during
      1993 through 2006 because of injury were checked against the National Cause of
      Death Register in Sweden. Standardised mortality ratio and confidence intervals
      were calculated. For the unnatural deaths that took place in Sweden, the police
      report, autopsy protocol, and hospital records, if present, were studied.
      RESULTS: Thirty-eight fatalities were included giving a standardised mortality
      ratio of 1.44 (95% CI: 1.02-1.98). A majority of the decedents were males (n=32,
      84%) and the median age at the time of death was 21 years. Twenty-three deaths
      were caused by unintentional injuries and ten by intentional injuries (all
      suicides), while five deaths were categorised as undetermined whether intentional
      or not. Seventy-four percent tested positive for either alcohol or drugs or a
      combination at the post mortem examination. Nine males and one female committed
      suicide, five tested positive for alcohol (one also for drugs), while four tested
      negative at the post mortem examination. One died abroad and in this case we lack
      information on alcohol and drugs. CONCLUSION: Teenagers visiting an emergency
      room due to injury experience an increased risk of premature death by unnatural
      cause and those at risk are especially males. The use of alcohol and drugs often
      seems to contribute to their untimely deaths. Identifying those at risk when they
      visit the emergency room for an injury and to take preventive actions at this
      stage could be a way to reduce the number of fatalities.

PMID- 22664706
TI  - Nonresponse analysis and adjustment in a mail survey on car accidents.
AB  - Statistical accident data plays an important role for traffic safety development
      involving the road system, vehicle design, and driver education. Vehicle
      manufacturers use data from accident mail surveys as an integral part of the
      product development process. Low response rates has, however, lead to concerns on
      whether estimates from a mail survey can be trusted as a source for making
      strategic decisions. The main objective of this paper was to investigate
      nonresponse bias in a mail survey addressing driver behaviour in accident
      situations. Insurance data, available for both respondents and nonrespondents
      were used to analyze, as well as adjust for nonresponse. Response propensity was
      investigated by using descriptive statistics and logistic regression analyses.
      The survey data was then weighted by using inverse propensity weights. Two
      specific examples of survey estimates are addressed, namely driver vigilance and
      driver's distraction just before the accident. The results from this paper reveal
      that driver age and accident type were the most influential variables for
      nonresponse weighting. Driver gender and size of town where the driver resides
      also had some influence, but not for all survey variables investigated. The main
      conclusion of this paper is that nonresponse weighting can increase confidence in
      accident data collected by a mail survey, especially when response rates are low.
      Weighting has a moderate influence on this survey, but a larger influence may be
      expected if applied on a more diverse driver population. The development of
      auxiliary data collection can further improve accident mail survey methodology in
      future.

PMID- 22664707
TI  - Associations between task, training and social environmental factors and error
      types involved in rail incidents and accidents.
AB  - Rail accidents can be understood in terms of the systemic and individual
      contributions to their causation. The current study was undertaken to determine
      whether errors and violations are more often associated with different local and
      organisational factors that contribute to rail accidents. The Contributing
      Factors Framework (CFF), a tool developed for the collection and codification of
      data regarding rail accidents and incidents, was applied to a sample of
      investigation reports. In addition, a more detailed categorisation of errors was
      undertaken. Ninety-six investigation reports into Australian accidents and
      incidents occurring between 1999 and 2008 were analysed. Each report was coded
      independently by two experienced coders. Task demand factors were significantly
      more often associated with skill-based errors, knowledge and training
      deficiencies significantly associated with mistakes, and violations significantly
      linked to social environmental factors.

PMID- 22664708
TI  - Older drivers' crashes in Queensland, Australia.
AB  - BACKGROUND: The growing proportion of older adults in Australia is predicted to
      comprise 23% of the population by 2030. Accordingly, an increasing number of
      older drivers and fatal crashes of these drivers could also be expected. While
      the cognitive and physiological limitations of ageing and their road safety
      implications have been widely documented, research has generally considered older
      drivers as a homogeneous group. Knowledge of age-related crash trends within the
      older driver group itself is currently limited. OBJECTIVE: The aim of this
      research was to identify age-related differences in serious road crashes of older
      drivers. This was achieved by comparing crash characteristics between older and
      younger drivers and between sub-groups of older drivers. Particular attention was
      paid to serious crashes (crashes resulting in hospitalisation and fatalities) as
      they place the greatest burden on the Australian health system. METHOD: Using
      Queensland Crash data, a total of 191,709 crashes of all-aged drivers (17-80+)
      over a 9-year period were analysed. Crash patterns of drivers' aged 17-24, 25-39,
      40-49, 50-59, 60-69, 70-79 and 80+ were compared in terms of crash severity
      (e.g., fatal), at fault levels, traffic control measures (e.g., stop signs) and
      road features (e.g., intersections). Crashes of older driver sub-groups (60-69,
      70-79, 80+) were also compared to those of middle-aged drivers (40-49 and 50-59
      combined, who were identified as the safest driving cohort) with respect to crash
      related traffic control features and other factors (e.g., speed). Confounding
      factors including speed and crash nature (e.g., sideswipe) were controlled for.
      RESULTS AND DISCUSSION: Results indicated that patterns of serious crashes, as a
      function of crash severity, at-fault levels, road conditions and traffic control
      measures, differed significantly between age groups. As a group, older drivers
      (60+) represented the greatest proportion of crashes resulting in fatalities and
      hospitalisation, as well as those involving uncontrolled intersections and
      failure to give way. The opposite was found for middle-aged drivers, although
      they had the highest proportion of alcohol and speed-related crashes when
      compared to older drivers. Among all older drivers, those aged 60-69 were least
      likely to be involved in or the cause of crashes, but most likely to crash at
      interchanges and as a result of driving while fatigued or after consuming
      alcohol. Drivers aged 70-79 represented a mid-range level of crash involvement
      and culpability, and were most likely to crash at stop and give way signs.
      Drivers aged 80 years and beyond were most likely to be seriously injured or
      killed in, and at-fault for, crashes, and had the greatest number of crashes at
      both conventional and circular intersections. Overall, our findings highlight the
      heterogeneity of older drivers' crash patterns and suggest that age-related
      differences must be considered in measures designed to improve older driver
      safety.

PMID- 22664709
TI  - Road safety risk evaluation and target setting using data envelopment analysis
      and its extensions.
AB  - Currently, comparison between countries in terms of their road safety performance
      is widely conducted in order to better understand one's own safety situation and
      to learn from those best-performing countries by indicating practical targets and
      formulating action programmes. In this respect, crash data such as the number of
      road fatalities and casualties are mostly investigated. However, the absolute
      numbers are not directly comparable between countries. Therefore, the concept of
      risk, which is defined as the ratio of road safety outcomes and some measure of
      exposure (e.g., the population size, the number of registered vehicles, or
      distance travelled), is often used in the context of benchmarking. Nevertheless,
      these risk indicators are not consistent in most cases. In other words, countries
      may have different evaluation results or ranking positions using different
      exposure information. In this study, data envelopment analysis (DEA) as a
      performance measurement technique is investigated to provide an overall
      perspective on a country's road safety situation, and further assess whether the
      road safety outcomes registered in a country correspond to the numbers that can
      be expected based on the level of exposure. In doing so, three model extensions
      are considered, which are the DEA based road safety model (DEA-RS), the cross
      efficiency method, and the categorical DEA model. Using the measures of exposure
      to risk as the model's input and the number of road fatalities as output, an
      overall road safety efficiency score is computed for the 27 European Union (EU)
      countries based on the DEA-RS model, and the ranking of countries in accordance
      with their cross-efficiency scores is evaluated. Furthermore, after applying
      clustering analysis to group countries with inherent similarity in their
      practices, the categorical DEA-RS model is adopted to identify best-performing
      and underperforming countries in each cluster, as well as the reference sets or
      benchmarks for those underperforming ones. More importantly, the extent to which
      each reference set could be learned from is specified, and practical yet
      challenging targets are given for each underperforming country, which enables
      policymakers to recognize the gap with those best-performing countries and
      further develop their own road safety policy.

PMID- 22664710
TI  - Impact direction effect on serious-to-fatal injuries among drivers in near-side
      collisions according to impact location: focus on thoracic injuries.
AB  - Occupant injury in real world vehicle accidents can be significantly affected by
      a set of crash characteristics, of which impact direction and impact location (or
      damage location) in general scale interval (e.g., frontal impact is frequently
      defined as general damage to vehicle frontal end with impact angle range of 11-1
      o'clock) have been identified to associate with injury outcome. The effects of
      crash configuration in more specific scale of interval on the injury
      characteristics have not been adequately investigated. This paper presents a
      statistical analysis to investigate the combined effects of specific impact
      directions and impact locations on the serious-to-fatal injuries of driver
      occupants involved in near-side collisions using crash data from National
      Automotive Sampling System-Crashworthiness Data System (NASS-CDS) for the
      calendar years of 1995-2005. The screened injury dataset is categorized by three
      impact locations (side front, side center and side distributed) and two impact
      directions (oblique impact at 10 o'clock and pure lateral impact at 9 o'clock),
      resulting in six crash configurations in total. The weighted counts and the risks
      of different types of injuries in each subgroup are calculated, with which the
      relative risks along with 95% confidence intervals under oblique impacts versus
      lateral impacts in each impact location category are computed. Accordingly, the
      most frequent injury patterns, the risks and the coded-sources of serious
      thoracic injuries in different crash configurations are identified. The approach
      adopted in the present study provides new perspectives into occupant injury
      outcomes and associated mechanism. Results of the analyses reveal the importance
      of consideration of the crash configurations beyond the scope of existing side
      impact regulatory tests and stress the necessity of vehicle crashworthiness and
      restraint system design in omni-direction to better protect occupants in real
      world crash scenarios.

PMID- 22664711
TI  - Is the three-foot bicycle passing law working in Baltimore, Maryland?
AB  - Maryland (MD) recently became one of fourteen states in the United States to
      enact a traffic law requiring motor vehicles to pass bicyclists at a distance of
      greater than three feet. To our knowledge, motorist compliance with the law has
      never been assessed. This study measured the distance between overtaking motor
      vehicles and cyclists [e.g. vehicle passing distance (VPD)], to develop baseline
      metrics for tracking implementation of the three-foot passing law in Baltimore,
      MD and to assess risk factors for dangerous passes. During September and October
      2011, cyclists (n=5) measured VPD using a previously published video technique
      (Parkin and Meyers, 2010). Cyclists logged a total of 10.8h of video footage and
      586 vehicle passes on 34 bicycle commuting trips. The average trip lasted 19.5+/
      4.9 min and cyclists were passed on average 17.2+/-11.8 times per trip. VPDs of
      three feet or less were common when cycling in standard lanes (17%; 78 of 451
      passes) and lanes with a shared lane marking (e.g. sharrows) (23%; 11 of 47
      passes). No passes of three feet or less occurred in bicycle lanes (0 of 88
      passes). A multiple linear regression model was created, which explained 26% of
      the variability in VPD. Significant model variables were lane width, bicycle
      infrastructure, cyclist identity, and street identity. Interventions, such as
      driver education, signage, enforcement, and bicycle infrastructure changes are
      needed to influence driving behavior in Baltimore to increase motorist compliance
      with the three-foot law.

PMID- 22664712
TI  - Work-related injuries and musculoskeletal disorders among factory workers in a
      major city of China.
AB  - This study describes the frequency of occurrence of work-related injuries and
      musculoskeletal disorders (MSDs) among factory workers in Shenzhen, China, and
      examines the determinants of injuries and MSDs. A cross-sectional survey was
      conducted with 3479 frontline workers in 60 factories during 2008-2009. We
      calculated the annual incidence rates of work-related injuries and the prevalence
      rates of MSD (based on the Nordic Standard Form) for the factory workers.
      Logistic regression analysis was applied to explore the associations between
      potential risk factors and occupational injury and MSD. Among all participating
      workers, 8.3% reported acute traumatic injuries in the previous 12 months. The
      event-based incidence rate was 119.6 per 1000 person-years. About half of the
      frontline workers reported suffering from MSDs during the previous 12 months. The
      injury risk was reduced for female workers (Odds ratio, OR: 0.48; 95% confidence
      interval, CI: 0.36-0.66) and those with higher educational levels, but increased
      in workers with over 55 work hours/week (OR: 1.64; 95% CI: 1.21-2.22), high
      mental stress at work (OR: 3.50; 95% CI: 1.70-7.19) and previous injury history
      (OR: 3.94; 95% CI: 2.78-5.58). The MSD risk was increased among female workers
      (OR: 1.58; 95% CI: 1.34-1.87), and those with over 55 work hours/week (OR: 1.56;
      95% CI: 1.28-1.90), high mental stress at work (OR: 3.16; 95% CI: 2.04-4.89) and
      a past injury history (OR: 3.04; 95% CI: 2.14-4.32). High proportions of
      frontline workers were affected by work injuries and MSDs in these factories in
      China. Long work hours, high mental stress at work and previous injury history
      were important risk factors for work-related injury and MSD.

PMID- 22664713
TI  - The roles of exposure and speed in road safety analysis.
AB  - Speed is a determining factor in road safety analysis. It is generally believed
      that an increase in speed harms road safety. However, it can also be argued that
      driving at high speed reduces the length of time exposure and thus the likelihood
      of a crash. It is therefore critical to clarify the roles that exposure and speed
      play in road safety analysis. This study evaluates the relationship between speed
      and crash risk with respect to distance and time exposure, using disaggregated
      crash and speed data collected from 112 road segments in Hong Kong. A joint
      probability model based on a full Bayesian method is applied simultaneously to
      model crash occurrence and crash severity. In addition, we consider the
      explanatory variables, including road design, weather conditions, and temporal
      distribution, in the proposed crash prediction model. The results indicate that
      average speed plays a significant role in crash risk, despite opposing
      correlations with respect to distance and time exposure; the correlation between
      speed and crash risk is positive when distance exposure is considered, but
      negative when time exposure is used. However, in both cases, speed is positively
      associated with the injury severity.

PMID- 22664714
TI  - Driving in fog: the effects of driving experience and visibility on speed
      compensation and hazard avoidance.
AB  - Inexperience is one of the strongest predictors for collisions, but it remains
      unclear how novice drivers differ from experienced drivers in terms of safety
      related behavioural adaptations such as speed reduction in the presence of
      reduced visibility. To investigate the influence of driving experience on
      behavioural compensations to fog, average speed, speed variability, steering
      variability, collision rate, and hazard response time were measured in a driving
      simulator. Experienced drivers drove faster in clear visibility than novice
      drivers, yet they reduced their speed more in reduced visibility so that both
      groups drove at the same speed in simulated fog. Compared to experienced drivers,
      novice drivers had higher hazard response times, greater speed and steering
      variability, and were the only drivers to have collisions.

PMID- 22664715
TI  - Comparing the performance of residential fire sprinklers with other life-safety
      technologies.
AB  - Residential fire sprinklers have long proven themselves as life-safety
      technologies to the fire service community. Yet, about 1% of all one- and two
      family dwelling fires occur in homes protected by sprinklers. It has been argued
      that measured sprinkler performance has ignored factors confounding the
      relationship between sprinkler use and performance. In this analysis, sprinkler
      performance is measured by comparing 'like' structure fires, while conditioning
      on smoke detection technology and neighborhood housing and socioeconomic
      conditions, using propensity score matching. Results show that residential fire
      sprinklers protect occupant and firefighter health and safety, and are comparable
      to other life-safety technologies.

PMID- 22664716
TI  - The road user behaviour of school students in Belgium.
AB  - The present study aimed to investigate both the on road behaviour of Belgian
      school students and the validity of the Adolescent Road User Behaviour
      Questionnaire (ARBQ) in a sample of students attending school in Belgium. In
      total, 294 adolescents completed the ARBQ along with measures of their self
      reported accident involvement and sensation seeking behaviour. Confirmatory
      Factor Analysis supported the original factor structure of: "unsafe road
      crossing", "playing on the road" and "planned protective behaviour" for the 21
      item version of the questionnaire, but not for the full scale. Males were found
      to engage more often in unsafe crossing behaviour and playing on the roads. There
      were also age differences, with unsafe road crossing increasing with age and
      engagement in planned protective behaviours improving with age. Those who
      reported being involved in an accident also reported more frequent engagement in
      unsafe crossing, playing on the roads, thrill seeking behaviour and lower levels
      of behaviour inhibition. Therefore, this study confirms that the ARBQ is a useful
      tool for investigating safety-related behaviours that contribute to accident
      involvement.

PMID- 22664717
TI  - Using a multidimensional Rasch model approach to measure the police's perceived
      ability to detect, detain and intercept DWI vehicles when conducting sobriety
      checkpoints.
AB  - This study developed a scale to measure 502 Taiwan traffic police officers'
      perceived ability to detect, detain, and intercept those vehicles whose drivers
      are driving while intoxicated (DWI) when conducting sobriety checkpoints. Through
      factor analysis, the officers' enforcement ability was found to consist of two
      component latent traits: detecting ability (DA) and detaining and intercepting
      ability (DIA). A multidimensional approach of Rasch models was then applied to
      measure the police officers' perceived abilities and particular difficulties in
      conducting sobriety checkpoints. The study results indicated that the majority of
      police officers performed well in detecting DWI vehicles, but half of the study
      participants lacked confidence in detaining DWI vehicles and intercepting
      escaping DWI vehicles. DWI with weaving was found to be the most aggressive and
      threatening behavior to traffic police when conducting sobriety checkpoints.
      Police officers over age 46 were found to have significantly lower DA and DIA,
      while branch captains were found to have significantly higher DA than their
      colleagues. Several strategies and programs are suggested based on the study
      findings to improve the enforcement ability of police officers.

PMID- 22664718
TI  - Adolescent involvement in anti-social and delinquent behaviours: predicting
      future injury risk.
AB  - The purpose of this study was to challenge the broadly based focus of injury
      prevention strategies towards concern with the needs of young adolescents who
      engage in multiple anti-social and delinquent behaviours. Five hundred and forty
      13-14-year olds reported on injuries and truancy, violence, illegal road
      behaviours, drug, and alcohol use. Engagement in these behaviours was found to
      contribute to the likelihood of an injury. Those engaging in the most anti-social
      and delinquent behaviours were around five times more likely to report medically
      treated injuries in the past three months. Their likelihood of future injury was
      1.8 times more likely when they were followed up three months later. The
      engagement in multiple delinquent and illegal behaviours thus significantly
      increased the likelihood of injury and identifies a particularly vulnerable
      group. The findings also suggest that reaching these young people represents a
      key target for change strategies in injury prevention programs.

PMID- 22664719
TI  - Self-rated driving and driving safety in older adults.
AB  - Many U.S. states rely on older adults to self-regulate their driving and
      determine when driving is no longer a safe option. However, the relationship of
      older adults' self-rated driving in terms of actual driving competency outcomes
      is unclear. The current study investigates self-rated driving in terms of (1)
      systematic differences between older adults with high (good/excellent) versus low
      (poor/fair/average) self-ratings, and (2) the predictive nature of self-rated
      driving to adverse driving outcomes in older adults (n=350; mean age 73.9,
      SD=5.25, range 65-91). Adverse driving outcomes included self-reported incidences
      of (1) being pulled over by the police, (2) receiving a citation, (3) receiving a
      recommendation to cease or limit driving, (4) crashes, and (5) state-reported
      crashes. Results found that older drivers with low self-ratings reported more
      medical conditions, less driving frequency, and had been given more suggestions
      to stop/limit their driving; there were no other significant differences between
      low and high self-raters. Logistic regression revealed older drivers were more
      likely to have a state-reported crash and receive a suggestion to stop or limit
      driving. Men were more likely to report all adverse driving outcomes except for
      receiving a suggestion to stop or limit driving. Regarding self-rated driving,
      older adults with high ratings were 66% less likely (OR=0.34, 95% CI=0.14-0.85)
      to have received suggestions to limit or stop driving after accounting for
      demographics, health and driving frequency. Self-ratings were not predictive of
      other driving outcomes (being pulled over by the police, receiving a citation,
      self-reported crashes, or state-reported crashes, ps>0.05). Most older drivers
      (85.14%) rated themselves as either good or excellent drivers regardless of their
      actual previous citation or crash rates. Self-rated driving is likely not related
      to actual driving proficiency as indicated by previous crash involvement in older
      adults. Suggestions from other individuals to limit or cease driving may be more
      influential on self-ratings.

PMID- 22664720
TI  - Stress during puberty boosts metabolic activation associated with fear-extinction
      learning in hippocampus, basal amygdala and cingulate cortex.
AB  - Adolescence is characterized by major developmental changes that may render the
      individual vulnerable to stress and the development of psychopathologies in a sex
      specific manner. Earlier we reported lower anxiety-like behavior and higher risk
      taking and novelty seeking in rats previously exposed to peri-pubertal stress.
      Here we studied whether peri-pubertal stress affected the acquisition and
      extinction of fear memories and/or the associated functional engagement of
      various brain regions, as assessed with 2-deoxyglucose. We showed that while peri
      pubertal stress reduced freezing during the acquisition of fear memories
      (training) in both sexes, it had a sex-specific effect on extinction of these
      memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices
      showed higher metabolic rates during extinction in rats exposed to peri-pubertal
      stress. Interestingly, activation of the infralimbic cortex was negatively
      correlated with freezing during extinction only in control males, while only
      males stressed during puberty showed a significant correlation between behavior
      during extinction and metabolic activation of hippocampus, amygdala and
      paraventricular nucleus. No correlations between brain activation and behavior
      during extinction were observed in females (control or stress). These results
      indicate that exposure to peri-pubertal stress affects behavior and brain
      metabolism when the individual is exposed to an additional stressful challenge.
      Some of these effects are sex-specific.

PMID- 22664721
TI  - Impaired myocardial perfusion reserve in patients with fatty liver disease
      assessed by quantitative myocardial perfusion magnetic resonance imaging.
AB  - BACKGROUND: The purpose of this study was to determine whether the presence of
      fatty liver is associated with an alteration in myocardial perfusion reserve
      (MPR). METHODS AND RESULTS: A retrospective analysis of 65 asymptomatic subjects
      who underwent both plain abdominal computed tomography and cardiac magnetic
      resonance imaging (MRI), and who had normal left ventricular wall motion, no
      regional myocardial ischemia and no myocardial scar on MRI was performed. Stress
      and rest myocardial perfusion MRI were analyzed by Patlak plot method to quantify
      myocardial blood flow (MBF) and MPR in 16 myocardial segments. Fatty liver was
      detected in 18 (28%) of the 65 subjects. No significant difference was found in
      rest-MBF between subjects with and without fatty liver (1.2 +/- 0.75 vs. 1.1 +/-
      0.67 ml.min(-1).g(-1), P=0.59). However, MPR was significantly lower in subjects
      with fatty liver than the non-fatty liver subjects (2.3 +/- 0.74 vs. 3.3 +/- 1.4,
      P<0.001). Subjects with fatty liver had a higher prevalence of MPR <2.5 (78% vs.
      38%, P<0.005) and higher triglyceride levels (206 +/- 61 vs. 92 +/- 37 mg/dl,
      P<0.001). Multivariate analysis revealed the presence of fatty liver as a
      significant predictor of reduced MPR with an odds ratio of 8.2 (P<0.01).
      CONCLUSIONS: Nonalcoholic fatty liver disease is related to reduced MPR,
      suggesting impaired coronary microcirculation. 

PMID- 22664722
TI  - Radiofrequency catheter ablation of persistent atrial fibrillation decreases a
      sleep-disordered breathing parameter during a short follow-up period.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is often associated with atrial
      fibrillation (AF), but the impact of radiofrequency catheter ablation (RFCA) for
      AF on sleep apnea syndrome is unknown. METHODS AND RESULTS: A total of 25
      patients (3 women; 61 +/- 6 years) with sleep apnea syndrome who underwent RFCA
      for drug-refractory, persistent AF were studied. Polysomnography was also
      performed 1 day before and 1 week after RFCA in all patients. The total number of
      central or OSA or hypopnea events was analyzed and compared. Among the 25
      patients who all predominantly had obstructive apnea, the apnea-hypopnea index
      (AHI; median, 21, interquartile range [IQR]: 11-38 to median 15, IQR: 7-23;
      P=0.002) and obstructive type of apnea (median 10, IQR: 6-19 to median 7, IQR: 2
      14; P=0.003) decreased after RFCA. In patients in whom sinus rhythm was restored
      and maintained after RFCA, the AHI decreased after RFCA (median 22, IQR: 15-38 to
      median 15, IQR: 7-23; P<0.01), but it did not in those who had AF recurrence
      (median 10, IQR: 9-11 to median 11, IQR: 10-16; P<0.05). There was a significant
      correlation between the outcome of RFCA and % change in the AHI (rs=0.569,
      P=0.003). CONCLUSIONS: In patients with sleep apnea syndrome and AF, restoring
      sinus rhythm by RFCA was significantly associated with a decrease in AHI
      (Clinical Trial Registration: Trial number, UMIN000005538). 

PMID- 22664723
TI  - Sleep-disordered breathing is an independent risk factor of aborted sudden
      cardiac arrest in patients with coronary artery spasm.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) is often associated with sudden
      cardiac arrest (SCA) during sleep. Coronary artery spasm (CS) also occurs during
      sleep and is rarely associated with SCA, but the role of SDB in the risk of SCA
      is unknown in CS patients. This study evaluated the breathing patterns during
      sleep in CS patients with a prior history of aborted SCA. METHODS AND RESULTS:
      This study enrolled 24 patients (age 61.6 +/- 11.0 years, male/female 19/5) with
      CS proven by an acetylcholine provocation test. They were divided into 2 groups:
      prior history of aborted SCA due to fatal arrhythmia (SCA group; n=9) and no such
      history (no-SCA group; n=15). Patients underwent overnight polysomnography with
      ambulatory electrocardiography. The overall prevalence of SDB (apnea hypopnea
      index >=15) was 45.8% in this cohort. SDB was more frequent in the SCA group than
      in the no-SCA group (88.9% vs. 20.0% P=0.001) and identified as a pivotal risk
      factor of aborted SCA (odds ratio: 38.9, 95% CI: 2.80-1,498.2, P=0.01). Very-low
      frequency was significantly correlated with the apnea hypopnea index in patients
      with SCA (P=0.01, r=0.78) during sleep. CONCLUSIONS: SDB is a significant risk
      factor for SCA in CS patients and autonomic instability during sleep might be
      involved in this association.

PMID- 22664724
TI  - Latest evidence in endothelium-derived hyperpolarizing factor research.

PMID- 22664725
TI  - The Cardiological Society of India.

PMID- 22664726
TI  - ATAD3B is a human embryonic stem cell specific mitochondrial protein, re
      expressed in cancer cells, that functions as dominant negative for the ubiquitous
      ATAD3A.
AB  - Here we report on the identification of a human pluripotent embryonic stem cell
      (hESC) specific mitochondrial protein that is re-expressed in cancer cells,
      ATAD3B. ATAD3B belongs to the AAA+ ATPase ATAD3 protein family of mitochondrial
      proteins specific to multicellular eukaryotes. Using loss- and gain-of-function
      approaches, we show that ATAD3B associates with the ubiquitous ATAD3A species,
      negatively regulates the interaction of ATAD3A with matrix nucleoid complexes and
      contributes to a mitochondria fragmentation phenotype. We conclude that ATAD3B is
      a negative regulator of ATAD3A and may function as an adaptor of mitochondrial
      homeostasis and metabolism in hESCs and cancer cells.

PMID- 22664727
TI  - Berbamine protects the heart from ischemia/reperfusion injury by maintaining
      cytosolic Ca(2+) homeostasis and preventing calpain activation.
AB  - BACKGROUND: Berbamine, a natural compound from Barberry, was reported to protect
      myocardium from ischemia/reperfusion (I/R) injury, but the underlying mechanisms
      are largely unknown. METHODS AND RESULTS: Berbamine pretreatment from 10 to
      100nmol/L concentration-dependently improved post-ischemic myocardial function.
      Similar protection was confirmed in isolated cardiomyocytes characterized by the
      attenuation of I/R-induced intracellular free Ca(2+) concentration ([Ca(2+)](i))
      overloading and the depression of cell shortening and Ca(2+) transients, which
      were partially mimicked but not augmented by calpain inhibitor calpeptin and
      abolished by mitochondrial ATP-sensitive potassium (mitoK(ATP) channel inhibitor
      5-hydroxydecanoate (5-HD) and phosphoinositide 3-kinase (PI3K) inhibitor
      wortmannin. Consistently, I/R-induced increase of calpain activity and decrease
      of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) activity; and protein expression
      of SERCA2a, desmin, calpastatin and Akt was significantly attenuated by
      berbamine. In addition, I/R-decreased Akt protein was reversed by calpeptin.
      Moreover, berbamine further increased I/R-enhanced phosphorylation of Akt and
      glycogen synthase kinase-3beta (GSK3beta). These protections were abolished by
      wortmannin. Furthermore, berbamine significantly attenuated I/R-induced lactate
      dehydrogenase release, infarct size and contractile dysfunction, and such
      cardioprotective actions were abolished by wortmannin and 5-HD or mimicked by
      glycogen synthase kinase-3beta (GSK3beta) inhibitor SB216763 but without additive
      effect. CONCLUSIONS: These findings suggest that berbamine confers
      cardioprotection against I/R injury by attenuating [Ca(2+)inf(i) overloading and
      preventing calpain activation through the activation of the PI3K-Akt-GSK3beta
      pathway and, subsequently, opening of the mitoK(ATP) channel.

PMID- 22664728
TI  - Introduction to the special issue: special issue: presentations at the 11th
      European Workshop on Astrobiology "Planets and life: evolution and distribution",
      11-14 July 2011,Koln, Germany.

PMID- 22664729
TI  - Vertebral and/or basilar dolichoectasia in human adult cadavers.
AB  - BACKGROUND: Intracranial arterial dolichoectasia is a condition in which arteries
      demonstrate an increase in length and diameter, with the vertebrobasilar system
      being the most commonly affected segment. Because the criteria for and degree of
      vertebrobasilar dolichoectasia are usually established on three-dimensional time
      of-flight MR angiography, we presented the results of an anatomic study of
      vertebrobasilar dolichoectasia cadaveric specimens. METHOD: Examination was
      carried out on the brains of human adult cadavers, routinely dissected at the
      Institute of Forensic Medicine. Measurement of the outer diameter and length of
      vertebral and/or basilar arteries was performed using the ImageJ processing
      program. RESULTS: There were 14 cases (14/216) of vertebral and/or basilar
      (dolicho)ectasia. Their classification into special (sub)types is made according
      to the basilar and/or vertebral diameter. The basilar length ranged from 32.91
      59.37 mm, and the basilar outer diameter ranged from 3.51-8.92 mm in relation to
      the corresponding point of its measurement. The outer diameter of the vertebral
      arteries ranged from 0.67-5.91 mm. The Games-Howell post hoc test additionally
      showed that a basilar outer diameter of grade III and IV was significantly larger
      than in grade II (p < 0.05). CONCLUSIONS: We noted a predisposition of males
      older than 40 years to arterial dolichoectasia in the vertebrobasilar system,
      independently from population group, as well as its asymptomatic appearance,
      independently from the presence of atherosclerotic plaques.

PMID- 22664730
TI  - Role of protein kinase Cu isoform expression in dimethylhydrazine-induced
      vascular endothelial proliferation.
AB  - 1,2-Dimethylthdrazine (DMH) has been known to induce vascular neoplasms, such as
      malignant endothelioma, in animal experiments through the induction of abnormal
      proliferation of human umbilical vein endothelial cells (HUVECs). We studied the
      effect of protein kinase C (PKC) isoforms on DMH-induced abnormal proliferation
      of vascular endothelium to identify the isoforms with higher relevance. The study
      was conducted with pure culture HUVECs in a control group and a 1x10-9 M DMH
      treated group. The mRNA and protein expression of PKC isoforms in DMH-treated
      HUVECs was evaluated by reverse transcription-polymerase chain reaction and
      western blotting. DMH-induced PKC production was detected by a PKC activity
      assay. To investigate the role of the PKC isoforms in DMH-induced abnormal HUVEC
      proliferation, we modulated PKCu expression in DMH-treated HUVECs using small
      interfering RNA. We determined the expression of 11 PKC isoforms by PCR analysis
      in both the control and DMH-treated groups, and the results were statistically
      analyzed to detect any differences. According to the results, both groups
      expressed 6 out of 11 isoforms. Expression of PKCu was significant in the DMH
      treated group, and downregulation of PKCu inhibited DMH-induced abnormal HUVEC
      proliferation. The PKCu isoform is believed to be important in the abnormal
      growth of vascular endothelial cells induced by DMH, and this was confirmed by an
      objective siRNA experiment, which showed a clear decrease in PKCu expression.
      Therefore, it is believed that PKCu is a key factor in the abnormal proliferation
      of vascular endothelial cells, and these results can be used as fundamental
      research data for abnormal vessel development or the embryologic mechanisms of
      vessel development.

PMID- 22664735
TI  - Coronary artery disease: Off-pump CABG can improve outcomes in patients with CKD.

PMID- 22664737
TI  - Azithromycin decolonization of STEC--a new risk emerges.

PMID- 22664736
TI  - Complications of long-term therapy for ANCA-associated systemic vasculitis.
AB  - The antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitides
      (AASVs) include granulomatosis with polyangiitis and microscopic polyangiitis.
      These conditions are characterized by small-vessel inflammation and necrosis,
      predominantly in pulmonary and renal vascular beds. Untreated AASV has a poor
      prognosis, although the advent of effective immunosuppressive therapy (the
      mainstay of which remains cyclophosphamide with high-dose corticosteroids) has
      markedly improved patients' survival (78% at 5 years). Patients with AASV,
      however, continue to have an increased mortality compared to the general
      population. Mortality is greatest in the first year after diagnosis and remains
      consistently elevated in subsequent years. Patients with AASV also experience
      increased rates of infections, malignancies and cardiovascular events as compared
      to the general population. Current treatments for AASV, although effective in
      controlling the aggressive systemic disease, incur substantial long-term toxic
      effects. Long-term immunosuppressive therapy also has notable deleterious effects
      on bone health and fertility. The long-term safety profiles of biological
      therapies (such as rituximab) are yet to be evaluated in patients with AASV, but
      represent a promising treatment option. The challenge for the future is to
      develop specific therapies with improved safety profiles that can cure these
      diseases.

PMID- 22664738
TI  - Propylthiouracil-induced antineutrophil cytoplasmic antibody-associated
      vasculitis.
AB  - Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) refers to
      a group of potentially life-threatening autoimmune diseases. A recent development
      in this field is the recognition that certain drugs can induce AAV. Among these
      agents, the drug most often implicated in causing disease is the commonly used
      antithyroid agent propylthiouracil (PTU). This Review provides an update on PTU
      induced AAV. Clinical characteristics of PTU-induced AAV are similar to that of
      primary AAV, but usually have a milder course and better prognosis, provided
      early cessation of the disease-causing drug. PTU-induced ANCAs usually react to
      several components of myeloid granules, which is helpful in differentiating PTU
      induced AAV from primary AAV. Early cessation of PTU is crucial in the treatment
      of PTU-induced AAV. The duration of immunosuppressive therapy might be shorter
      than in primary AAV, depending on the severity of organ damage, and maintenance
      therapy is not always necessary.

PMID- 22664739
TI  - Klotho as a potential biomarker and therapy for acute kidney injury.
AB  - Klotho is a single-pass transmembrane protein that is highly expressed in the
      kidney and is known to act as a coreceptor for fibroblast growth factor 23. The
      extracellular domain can be produced independently or shed from membrane-bound
      Klotho and functions as an endocrine substance with multiple functions including
      antioxidation, modulation of ion transport, suppression of fibrosis, and
      preservation of stem cells. Emerging evidence has revealed that Klotho deficiency
      is an early event in acute kidney injury (AKI), and a pathogenic factor that
      exacerbates acute kidney damage and contributes to long-term consequences.
      Restoration by exogenous supplementation or stimulation of endogenous Klotho
      might prevent and ameliorate injury, promote recovery, and suppress fibrosis to
      mitigate development of chronic kidney disease. Although data are still emerging,
      in this Perspectives article we discuss why this renal-derived protein is a
      highly promising candidate as both an early biomarker and therapeutic agent for
      AKI.

PMID- 22664740
TI  - Systemic delivery of human mesenchymal stromal cells combined with IGF-1 enhances
      muscle functional recovery in LAMA2 dy/2j dystrophic mice.
AB  - The combination of cell therapy with growth factors could be a useful approach to
      treat progressive muscular dystrophies. Here, we demonstrate, for the first time,
      that IGF-1 considerably enhances the myogenesis of human umbilical cord (UC)
      mesenchymal stromal cells (MSCs) in vitro and that IGF-1 enhances interaction and
      restoration of dystrophin expression in co-cultures of MSCs and muscle cells from
      Duchenne patients. In vivo studies showed that human MSCs were able to reach the
      skeletal muscle of LAMA2(dy/2j) dystrophic mice, through systemic delivery,
      without immunosuppression. Moreover, we showed, for the first time, that IGF-1
      injected systemically together with MSCs markedly reduced muscle inflammation and
      fibrosis, and significantly improved muscle strength in dystrophic mice. Our
      results suggest that a combined treatment with IGF-1 and MSCs enhances efficiency
      of muscle repair and, therefore, should be further considered as a potential
      therapeutic approach in muscular dystrophies.

PMID- 22664741
TI  - Generation of Schwann cell-derived multipotent neurospheres isolated from intact
      sciatic nerve.
AB  - Schwann cells (SCs) are the supporting cells of the peripheral nervous system and
      originate from the neural crest. They play a unique role in the regeneration of
      injured peripheral nerves and have themselves a highly unstable phenotype as
      demonstrated by their unexpectedly broad differentiation potential. Thus, SCs can
      be considered as dormant, multipotent neural crest-derived progenitors or stem
      cells. Upon injury they de-differentiate via cellular reprogramming, re-enter the
      cell cycle and participate in the regeneration of the nerve. Here we describe a
      protocol for efficient generation of neurospheres from intact adult rat and
      murine sciatic nerve without the need of experimental in vivo pre-degeneration of
      the nerve prior to Schwann cell isolation. After isolation and removal of the
      connective tissue, the nerves are initially plated on poly-D-lysine coated cell
      culture plates followed by migration of the cells up to 80% confluence and a
      subsequent switch to serum-free medium leading to formation of multipotent
      neurospheres. In this context, migration of SCs from the isolated nerve, followed
      by serum-free cultivation of isolated SCs as neurospheres mimics the injury and
      reprograms fully differentiated SCs into a multipotent, neural crest-derived stem
      cell phenotype. This protocol allows reproducible generation of multipotent
      Schwann cell-derived neurospheres from sciatic nerve through cellular
      reprogramming by culture, potentially marking a starting point for future
      detailed investigations of the de-differentiation process.

PMID- 22664742
TI  - Evaluation of pulmonary embolism in the emergency department and consistency with
      a national quality measure: quantifying the opportunity for improvement.
AB  - BACKGROUND: The National Quality Forum (NQF) has endorsed a performance measure
      designed to increase imaging efficiency for the evaluation of pulmonary embolism
      (PE) in the emergency department (ED). To our knowledge, no published data have
      examined the effect of patient-level predictors on performance. METHODS: To
      quantify the prevalence of avoidable imaging in ED patients with suspected PE, we
      performed a prospective, multicenter observational study of ED patients evaluated
      for PE from 2004 through 2007 at 11 US EDs. Adult patients tested for PE were
      enrolled, with data collected in a standardized instrument. The primary outcome
      was the proportion of imaging that was potentially avoidable according to the NQF
      measure. Avoidable imaging was defined as imaging in a patient with low pretest
      probability for PE, who either did not have a D-dimer test ordered or who had a
      negative D-dimer test result. We performed subanalyses testing alternative
      pretest probability cutoffs and imaging definitions on measure performance as
      well as a secondary analysis to identify factors associated with inappropriate
      imaging. chi(2) Test was used for bivariate analysis of categorical variables and
      multivariable logistic regression for the secondary analysis. RESULTS: We
      enrolled 5940 patients, of whom 4113 (69%) had low pretest probability of PE.
      Imaging was performed in 2238 low-risk patients (38%), of whom 811 had no D-dimer
      testing, and 394 had negative D-dimer test results. Imaging was avoidable,
      according to the NQF measure, in 1205 patients (32%; 95% CI, 31%-34%). Avoidable
      imaging owing to not ordering a D-dimer test was associated with age (odds ratio
      [OR], 1.15 per decade; 95% CI, 1.10-1.21). Avoidable imaging owing to imaging
      after a negative D-dimer test result was associated with inactive malignant
      disease (OR, 1.66; 95% CI, 1.11-2.49). CONCLUSIONS: One-third of imaging
      performed for suspected PE may be categorized as avoidable. Improving adherence
      to established diagnostic protocols is likely to result in significantly fewer
      patients receiving unnecessary irradiation and substantial savings.

PMID- 22664743
TI  - Downregulation of IRS-1 promotes metastasis of head and neck squamous cell
      carcinoma.
AB  - Lymph node metastasis is responsible for the high morbidity of head and neck
      squamous cell carcinoma (HNSCC). To date, the role of insulin receptor substrate
      1 (IRS-1) in tumorigenesis and metastasis of head and neck cancer has not been
      elucidated. In this study, we found a negative correlation of IRS-1 expression
      with tumor metastasis both in human tissue samples and in cell lines.
      Furthermore, we found that knockdown of IRS-1 expression enhanced cell invasive
      potency and induced EMT in parallel with upregulation of miR-9 expression. We
      propose that IRS-1 suppresses metastasis of head and neck cancer possibly through
      miR-9.

PMID- 22664744
TI  - Rewarming after therapeutic hypothermia.

PMID- 22664745
TI  - Effect of N-acetylcysteine (NAC) on acute lung injury and acute kidney injury in
      hemorrhagic shock.
AB  - AIM OF THE STUDY: N-acetylcysteine (NAC) has been investigated to attenuate organ
      injury in various experimental and clinical studies. However, results in
      hemorrhagic shock (HS) were controversial. We determined the effects of
      continuous administration of NAC on acute lung injury (ALI) and acute kidney
      injury (AKI) in HS model. METHODS: Twenty male Sprague-Dawley rats were used.
      Pressure controlled HS model defined by mean arterial pressure (MAP) 40+/-2 mmHg
      for 90 min followed by resuscitation and observation was used. Rats (n=10 per
      group) were randomized into 2 groups with NAC or dextrose. Intravenous NAC was
      given continuously from 15 min after induction of HS to the end of observation
      period (2 h). We measured serum IL-6, nitrite/nitrate concentration. NF-kappaB
      p65 DNA binding activity, expressions of cytoplasmic phosphorylated IkappaB-alpha
      (p-IkappaB-alpha) and IkappaB-alpha, malondialdehyde (MDA) and histopathological
      injury scores in lung and kidney were also evaluated. RESULTS: MAP did not show
      any difference during the study period. NAC decreased histopathologic scores in
      both lung and kidney. Lung and kidney MDA levels were significantly lower in the
      NAC group compared to control group. Serum nitrite/nitrate and IL-6 were also
      significantly lower in the NAC group. The levels of lung cytoplasmic p-IkappaB
      alpha expression was mitigated by NAC, and NF-kappaB p65 DNA binding activity was
      also significantly decreased in the NAC group. CONCLUSIONS: Continuous infusion
      of NAC attenuated inflammatory response and acute lung and kidney injury after
      hemorrhagic shock in rats.

PMID- 22664746
TI  - Endotracheal intubation versus supraglottic airway insertion in out-of-hospital
      cardiac arrest.
AB  - OBJECTIVE: To simplify airway management and minimize cardiopulmonary
      resuscitation (CPR) chest compression interruptions, some emergency medical
      services (EMS) practitioners utilize supraglottic airway (SGA) devices instead of
      endotracheal intubation (ETI) as the primary airway adjunct in out-of-hospital
      cardiac arrest (OHCA). We compared the outcomes of patients receiving ETI with
      those receiving SGA following OHCA. METHODS: We performed a secondary analysis of
      data from the multicenter Resuscitation Outcomes Consortium (ROC) PRIMED trial.
      We studied adult non-traumatic OHCA receiving successful SGA insertion (King
      Laryngeal Tube, Combitube, and Laryngeal Mask Airway) or successful ETI. The
      primary outcome was survival to hospital discharge with satisfactory functional
      status (Modified Rankin Scale <=3). Secondary outcomes included return of
      spontaneous circulation (ROSC), 24-h survival, major airway or pulmonary
      complications (pulmonary edema, internal thoracic or abdominal injuries, acute
      lung injury, sepsis, and pneumonia). Using multivariable logistic regression, we
      studied the association between out-of-hospital airway management method (ETI vs.
      SGA) and OHCA outcomes, adjusting for confounders. RESULTS: Of 10,455 adult OHCA,
      8487 (81.2%) received ETI and 1968 (18.8%) received SGA. Survival to hospital
      discharge with satisfactory functional status was: ETI 4.7%, SGA 3.9%. Compared
      with successful SGA, successful ETI was associated with increased survival to
      hospital discharge (adjusted OR 1.40; 95% CI: 1.04, 1.89), ROSC (adjusted OR
      1.78; 95% CI: 1.54, 2.04) and 24-h survival (adjusted OR 1.74; 95% CI: 1.49,
      2.04). ETI was not associated with secondary airway or pulmonary complications
      (adjusted OR 0.84; 95% CI: 0.61, 1.16). CONCLUSIONS: In this secondary analysis
      of data from the multicenter ROC PRIMED trial, ETI was associated with improved
      outcomes over SGA insertion after OHCA.

PMID- 22664747
TI  - Endogenous glucocorticoids promote the expansion of myeloid-derived suppressor
      cells in a murine model of trauma.
AB  - Stress-dose of glucocorticoid has been demonstrated to be beneficial for trauma
      patients in clinical studies. Recently, a heterogeneous population of myeloid
      cells with immunosuppressive activity named myeloid-derived suppressor cells
      (MDSCs) has been found to accumulate in the trauma host and can be induced by
      glucocorticoids in vitro. In order to explore the effect of endogenous
      glucocorticoids on MDSCs under trauma conditions, we blocked the glucocorticoid
      signal in a murine trauma model using the antagonist of the glucocorticoid
      receptor RU486 (mifepristone). We found for the first time that RU486 not only
      blunted MDSC expansion induced by trauma in the spleen, peripheral blood and bone
      marrow especially at 6 h after traumatic stress but also decreased the survival
      rate from 100 to 20% in traumatic mice within 7 days. Moreover, neither MDSCs
      producing arginase-1 nor the morphological characterization of trauma-induced
      MDSCs was affected by the blockage of the glucocorticoid receptor. Our results
      suggest that endogenous glucocorticoids may promote MDSCs expansion in a murine
      trauma model and MDSCs may be beneficial for the trauma host.

PMID- 22664748
TI  - Exposure to environmental endocrine disruptors and child development.

PMID- 22664749
TI  - A randomized, double-blind, placebo-controlled, dose-response study to assess the
      pharmacokinetics, efficacy, and safety of gabapentin enacarbil in subjects with
      restless legs syndrome.
AB  - OBJECTIVE: The objective of this study was to determine steady-state gabapentin
      exposures and corresponding relief of symptoms and safety profile produced by 4
      dose levels of gabapentin enacarbil (GEn) in subjects with restless legs syndrome
      (RLS). METHODS: Subjects with RLS (n = 217) were randomized to receive once
      daily, orally administered GEn 600 (n = 48), 1200 (n = 45), 1800 (n = 38), or
      2400 mg (n = 45) or placebo (n = 41) in this 12-week, double-blind, multicenter
      study (NCT01332305). Clinic visits were at screening, baseline, and weeks 1, 2,
      3, 4, 6, 8, 10, and 12; plasma gabapentin concentrations were measured by a
      validated liquid chromatography-mass spectrometry/mass spectrometry method at
      weeks 4 and 12. RESULTS: Exposure to gabapentin was proportional to GEn dose.
      Time to maximum plasma concentration was 7 to 9 hours, and elimination half-life
      was ~6 hours. The mean reduction from baseline to week 12 in International
      Restless Legs Syndrome Rating Scale total score and proportions of subjects with
      "much improved"/"very much improved" Clinical Global Impression-Improvement
      scores (investigator and patient ratings) ranged from -12.9 to -13.9 for GEn
      treatment groups versus -9.3 for placebo. The 2 most commonly reported adverse
      events were somnolence and dizziness. CONCLUSIONS: Gabapentin exposure was
      approximately proportional to GEn dose. Efficacy data showed that a once-daily
      dose of GEn 600 to 2400 mg provides greater relief of RLS symptoms than placebo;
      GEn was generally well tolerated with an adverse event profile consistent with
      gabapentin.

PMID- 22664750
TI  - Impact of QseBC system in c-di-GMP-dependent quorum sensing regulatory network in
      a clinical isolate SSU of Aeromonas hydrophila.
AB  - Our earlier studies showed that AhyRI- (AI-1) and LuxS-based (AI-2) quorum
      sensing (QS) systems were positive and negative regulators of virulence,
      respectively, in a diarrheal isolate SSU of Aeromonas hydrophila. Recently, we
      demonstrated that deletion of the QseBC two-component signal transduction system
      (AI-3 QS in enterohemorrhagic Escherichia coli) also led to an attenuation of A.
      hydrophila in a septicemic mouse model of infection, and that interplay exists
      between AI-1, AI-2, and the second-messenger cyclic-di-guanosine monophosphate (c
      di-GMP) in modulating bacterial virulence. To further explore a network
      connection between all of the three QS systems in A. hydrophila SSU and their
      cross talk with c-di-GMP, we overproduced a protein with a GGDEF domain, which
      increases c-di-GMP levels in bacteria, and studied phenotypes and transcriptional
      profiling of genes involved in biofilm formation and motility of the wild-type
      (WT) A. hydrophila and its DeltaqseB mutant. Over-expression of the GGDEF domain
      encoding gene (aha0701h) resulted in a significantly reduced motility of the WT
      A. hydrophila similar to that of the DeltaqseB mutant. While enhanced protease
      production was noted in WT A. hydrophila that had increased c-di-GMP, no
      enzymatic activity was detected in the DeltaqseB mutant overexpressing the
      aha0701h gene. Likewise, denser biofilm formation was noted for WT bacteria when
      c-di-GMP was overproduced compared to its respective control; however,
      overproduction of c-di-GMP in the DeltaqseB mutant led to reduced biofilm
      formation, a finding similar to that noted for the parental A. hydrophila strain.
      These effects on bacterial motility and biofilm formation in the DeltaqseB mutant
      or the mutant with increased c-di-GMP were correlated with altered levels of fleN
      and vpsT genes. While we noted transcript levels of qseB and qseC genes to be
      increased in the ahyRI mutant, down-regulation of the ahyR and ahyI genes was
      observed in the DeltaqseB mutant, which correlated with decreased protease
      activity. Finally, an enhanced virulence of WT A. hydrophila with increased c-di
      GMP was noted in a mouse model when compared to findings in the parental strain
      with vector alone. Overall, we conclude that cross talk between AI-1 and QseBC
      systems exists in A. hydrophila SSU, and c-di-GMP modulation on QseBC system is
      dependent on the expression of the AI-1 system.

PMID- 22664751
TI  - Reduced graft-versus-host disease in C3-deficient mice is associated with
      decreased donor Th1/Th17 differentiation.
AB  - Graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell
      transplantation is mediated by the activation of recipient dendritic cells and
      subsequent proliferation of donor T cells. The complement system was recently
      shown to modulate adaptive immunity through an interaction of the complement
      system and lymphocytes. Complement proteins participate in the activation of
      dendritic cells, antigen presentation to T cells, and proliferation of T cells.
      Our studies with a murine model of bone marrow transplantation demonstrate that
      complement system regulates alloimmune responses in GVHD. Mice deficient in the
      central component of the complement system (C3(-/-)) had significantly lower GVHD
      related mortality and morbidity compared with wild-type recipient mice. The
      numbers of donor-derived T cells, including IFN-gamma(+), IL-17(+), and IL
      17(+)IFN-gamma(+) subsets, were decreased in secondary lymphoid organs of C3(-/-)
      recipients. Furthermore, the number of recipient CD8alpha(+)CD11c(+) cells in
      lymphoid organs was reduced. We conclude that C3 regulates Th1/17 differentiation
      in bone marrow transplantation, and define a novel function of the complement
      system in GVHD.

PMID- 22664752
TI  - Qualitative aspects and validation of a screening method for pesticides in
      vegetables and fruits based on liquid chromatography coupled to full scan high
      resolution (Orbitrap) mass spectrometry.
AB  - The analytical capabilities of liquid chromatography with single-stage high
      resolution mass spectrometry have been investigated with emphasis on qualitative
      aspects related to selective detection during screening and to identification.
      The study involved 21 different vegetable and fruit commodities, a screening
      database of 556 pesticides for evaluation of false positives, and a test set of
      130 pesticides spiked to the commodities at 0.01, 0.05, and 0.20 mg/kg for
      evaluation of false negatives. The final method involved a QuEChERS-based sample
      preparation (without dSPE clean up) and full scan acquisition using alternating
      scan events without/with fragmentation, at a resolving power of 50,000. Analyte
      detection was based on extraction of the exact mass (+/-5 ppm) of the major
      adduct ion at the database retention time +/-30 s and the presence of a second
      diagnostic ion. Various options for the additional ion were investigated and
      compared (other adduct ions, M + 1 or M + 2 isotopes, fragments). The two-ion
      approach for selective detection of the pesticides in the full scan data was
      compared with two alternative approaches based on response thresholds. Using the
      two-ion approach, the number of false positives out of 11,676 pesticide/commodity
      combinations targeted was 36 (0.3 %). The percentage of false negatives, assessed
      for 2,730 pesticide/commodity combinations, was 13 %, 3 %, and 1 % at the 0.01-,
      0.05-, and 0.20-mg/kg level, respectively (slightly higher with fully automated
      detection). Following the SANCO/12495/2011 protocol for validation of screening
      methods, the screening detection limit was determined for 130 pesticides and
      found to be 0.01, 0.05, and >=0.20 mg/kg for 86, 30, and 14 pesticides,
      respectively. For the detected pesticides in the spiked samples, the ability for
      unambiguous identification according to EU criteria was evaluated. A proposal for
      adaption of the criteria was made.

PMID- 22664753
TI  - Identification of biomarkers of stent restenosis with serum metabolomic profiling
      using gas chromatography/mass spectrometry.
AB  - BACKGROUND: Despite the establishment of guidelines for the secondary prevention
      of coronary artery diseases, many patients still develop restenosis after stent
      implantation. Therefore, novel and noninvasive serum biomarkers that can identify
      restenosis-prone conditions are necessary to improve the follow-up and treatment
      of patients with coronary artery disease. Of late, considerable attention is
      being focused on metabolomics, which is the comprehensive analysis of low
      molecular-weight metabolites. This study investigated the use of serum
      metabolomics in the identification of biomarkers of restenosis. METHODS AND
      RESULTS: Gas chromatography/mass spectrometry was used to obtain the serum
      metabolomic profiles of male patients hospitalized for follow-up coronary
      angiography 6 months after stent implantation; 23 patients presented with major
      restenotic lesions (>=75% obstruction), 47 with minor restenotic lesions (<=50%
      obstruction), and 16 with de novo atherosclerotic lesions. Of 83 serum
      metabolites analyzed, molecules - isobutylamine, sarcosine, homoserine, ribulose,
      taurine, glutamine, glucose, and tryptophan - in the major restenosis group were
      significantly different from those in the minor restenosis group. Differences in
      correlation among these metabolites imply possible alternations in the activated
      metabolic pathways. CONCLUSIONS: This study provides the first line of evidence
      for the use of serum metabolic profiling in the identification of specific
      biomarkers of stent restenosis.

PMID- 22664754
TI  - Effects of machine-assisted cycling on exercise capacity and endothelial function
      in elderly patients with heart failure.
AB  - BACKGROUND: Conventional exercise training (ET) for elderly patients with heart
      failure (HF) includes low-intensity stretching and gait training. The effects of
      2 types of low-intensity ET - machine-assisted cycling and conventional ET - on
      exercise capacity and endothelial function of elderly patients with HF was
      investigated in the present study. METHODS AND RESULTS: Twenty-seven elderly
      patients with HF (mean age: 79.5 years) were randomly assigned to either a
      machine-assisted cycling group or a conventional ET group. At baseline and after
      2 weeks of ET, all patients were tested for 6-minute walk distance (6MWD) and
      digital reactive hyperemia-peripheral arterial tonometry (RH-PAT). After 2 weeks
      of ET, a significant increase in 6MWD was observed in both groups with no
      significant difference between the groups. RH-PAT index significantly increased
      in patients aged <=80 (1.55+/-0.33 to 1.93+/-0.62, P=0.035) and a trend toward
      increase in RH-PAT index in the machine-assisted cycling group was observed
      (1.59+/-0.52 to 1.93+/-0.63, P=0.053), although no change was observed in the
      conventional ET group. In the multivariate model, patients' age and machine
      assisted cycling were associated with the increases in RH-PAT index (P<0.05).
      CONCLUSIONS: Machine-assisted cycling appeared to be as effective as conventional
      ET on exercise capacity in elderly patients with HF. Additionally, machine
      assisted cycling has the potential to improve endothelial function in these
      patients.

PMID- 22664755
TI  - Significance of coronary vasospasm in the perioperative management of non-cardiac
      surgery.
AB  - BACKGROUND: The number of patients undergoing non-cardiac surgery has been
      increasing. Thus, the reduction of cardiac events is important during the
      perioperative period. The prevalence of Japanese patients with coronary vasospasm
      is higher as compared with Western countries. The present study reported the role
      of coronary vasospasm in the perioperative period in a Japanese university
      hospital. METHODS AND RESULTS: A total of 77,745 consecutive patients who
      underwent non-cardiac surgery in Kumamoto University Hospital between April 2003
      and March 2010 were retrospectively examined. Forty-two cases in which patients
      underwent coronary catheterization due to cardiovascular events in the
      perioperative period were reviewed, and data were collected on the type of
      surgery, urgency of surgery, cardiac risk factors, previous history and the
      cardiology consultation. The Revised Cardiac Risk Index (RCRI) was also
      calculated. A total of 18 patients were diagnosed as having definite vasospastic
      angina. In the definite vasospastic angina group, 9 patients had cardiovascular
      events intraoperatively. Six patients were in the group undergoing high-risk
      surgery. The RCRI score in the definite vasospastic angina group was 0.5+/-0.6
      (mean+/-SEM), and only 2 patients had a preoperative consultation with a
      cardiologist. CONCLUSIONS: Coronary vasospasm is not often encountered, but it
      can be a cause of cardiac trouble in the perioperative period. It should be taken
      into consideration at the time of planning of operation in Japanese patients even
      if they apparently have low cardiac risk.

PMID- 22664756
TI  - Cholesterol metabolism in patients with hemodialysis in the presence or absence
      of coronary artery disease.
AB  - BACKGROUND: Little is known about the interrelationship between the lipid
      profile, cholesterol metabolism, and coronary risk factors in patients with
      hemodialysis (HD) in the presence or absence of coronary artery disease (CAD).
      METHODS AND RESULTS: Ninety-five patients with HD were selected (HD group). Fifty
      eight age-, gender-, and body mass index (BMI)-matched patients who had at least
      1 cardiovascular risk factor were selected as a non-HD group. Total cholesterol
      (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C), non-HDL-C, and the ratio of LDL-C to HDL-C (L/H)
      in the HD group were significantly lower than those in the non-HD group. All
      markers of cholesterol absorption (campesterol/TC, sitosterol/TC, and
      cholestanol/TC) and the ratio of campesterol to lathosterol in the HD group were
      significantly higher. In addition, in the HD group, L/H was negatively correlated
      with lathosterol/TC, campesterol/TC, sitosterol/TC, and cholestanol/TC. Finally,
      CAD was significantly associated with lathosterol/TC (P=0.028), which was
      positively associated with BMI in the HD group, whereas CAD was significantly
      associated only with hypertension (P=0.020) in the non-HD group. CONCLUSIONS: HD
      patients showed lower cholesterol concentrations than non-HD patients, and, as
      compensation, their cholesterol absorption might be accelerated. However, higher
      cholesterol synthesis, which was correlated with higher BMI, might be an
      independent predictor for the presence of CAD in HD patients.

PMID- 22664757
TI  - New human leukocyte antigen risk allele in Japanese patients with Takayasu
      arteritis.
AB  - BACKGROUND: The association of human leukocyte antigen (HLA) alleles and Takayasu
      arteritis (TA) is not fully understood. The aim of the present study was to
      investigate HLA alleles in Japanese patients with TA and the association of these
      alleles with clinical manifestations. METHODS AND RESULTS: A total of 96 patients
      diagnosed with TA according to the Guideline for Management of Vasculitis
      Syndrome (Japanese Circulation Society 2008) and 371 healthy controls were
      enrolled in the present study. HLA genotyping showed a significant association of
      HLA-B67 (P=0.00024, odds ratio [OR]=4.94), a novel locus, and B52 (P<0.0001;
      OR=3.35), a conventional locus, with TA using both sequence-based typing and PCR
      SSP assay. The frequency of HLA-B39, an allele reportedly associated with TA in
      Asian populations, was not higher than controls in the present study (P=0.86,
      OR=1.07). B52 had higher prevalence than B67 but the OR was higher for B67. We
      next studied the association of HLA-B67 and -B52 with clinical characteristics:
      age at disease onset, distribution of arteritis, pulmonary involvement, aortic
      regurgitation, systemic hypertension, steroid resistance and recurrence rate in
      TA. There was no significant difference in these clinical parameters between HLA
      B67-positive or HLA-B52-positive patients and other patients. CONCLUSIONS: The
      HLA-B67 allele could be a new and important marker of TA because of its high OR
      compared to HLA-B52, although its prevalence in TA is lower.

PMID- 22664758
TI  - Engineering a bilayered hydrogel to control ASC differentiation.
AB  - Natural polymers over the years have gained more importance because of their host
      biocompatibility and ability to interact with cells in vitro and in vivo. An area
      of research that holds promise in regenerative medicine is the combinatorial use
      of novel biomaterials and stem cells. A fundamental strategy in the field of
      tissue engineering is the use of three-dimensional scaffold (e.g., decellularized
      extracellular matrix, hydrogels, micro/nano particles) for directing cell
      function. This technology has evolved from the discovery that cells need a
      substrate upon which they can adhere, proliferate, and express their
      differentiated cellular phenotype and function. More recently, it has also been
      determined that cells not only use these substrates for adherence, but also
      interact and take cues from the matrix substrate (e.g., extracellular matrix,
      ECM). Therefore, the cells and scaffolds have a reciprocal connection that serves
      to control tissue development, organization, and ultimate function. Adipose
      derived stem cells (ASCs) are mesenchymal, non-hematopoetic stem cells present in
      adipose tissue that can exhibit multi-lineage differentiation and serve as a
      readily available source of cells (i.e. pre-vascular endothelia and pericytes).
      Our hypothesis is that adipose-derived stem cells can be directed toward
      differing phenotypes simultaneously by simply co-culturing them in bilayered
      matrices. Our laboratory is focused on dermal wound healing. To this end, we
      created a single composite matrix from the natural biomaterials, fibrin,
      collagen, and chitosan that can mimic the characteristics and functions of a
      dermal-specific wound healing ECM environment.

PMID- 22664759
TI  - WHO reform creeps forward.

PMID- 22664760
TI  - People, planet and profits: the case for greening operating rooms.

PMID- 22664761
TI  - Farm-grown superbugs: while the world acts, Canada dawdles.

PMID- 22664762
TI  - Inching toward universal nutrient disclosure.

PMID- 22664763
TI  - Acetaminophen overdose in children.

PMID- 22664764
TI  - Infoway to become more responsive to needs, CEO vows.

PMID- 22664765
TI  - Pituitary apoplexy masquerading as bacterial meningitis.

PMID- 22664766
TI  - Binding R&D convention put on hold.

PMID- 22664768
TI  - A move toward self-medication in the United States.

PMID- 22664769
TI  - Impact of continuous positive airway pressure on C-reactive protein in patients
      with obstructive sleep apnea: a meta-analysis.
AB  - PURPOSE: C-reactive protein (CRP) is associated with the development of
      obstructive sleep apnea (OSA) and cardiovascular diseases. Continuous positive
      airway pressure (CPAP) is an effective treatment for OSA, but the impact of CPAP
      therapy on CRP levels in patients with OSA remains unclear. To obtain this
      information, we performed a meta-analysis to determine whether effective CPAP
      therapy could reduce serum CRP levels. METHODS: A comprehensive literature search
      was performed to identify studies that examined the impact of CPAP on serum CRP
      levels in OSA patients who were treated with CPAP for at least 4 weeks.
      Standardized mean difference (SMD) was used to analyze the summary estimates for
      CPAP therapy. RESULTS: Fourteen self-control design studies involving 1199
      patients with OSA met the inclusion criteria. Meta-analysis indicated that the
      overall SMD for the CRP levels was 0.64 units (95 % confidence interval (CI) 0.40
      to 0.88) before and after CPAP therapy; test for overall effect z = 5.27 (P =
      0.000). Subgroup analysis showed that evolution of CRP decreased non
      significantly in less than 3 months (SMD, 0.26, 95 % CI -0.08 to 0.60, P =
      0.138), significantly decreased after 3 months (SMD, 0.68, 95 % CI 0.34 to 1.02,
      P = 0.000), and further declined after 6 months (SMD, 0.74, 95 % CI 0.43 to 1.05,
      P = 0.000). CONCLUSIONS: The systemic inflammation, as measured by CRP, was
      present and significantly reduced by effective CPAP therapy in patients with OSA.
      The use of CRP levels may be clinically recognized as a valuable predictor for
      OSA treatment monitoring.

PMID- 22664770
TI  - Ocular surface assessment in patients with obstructive sleep apnea-hypopnea
      syndrome.
AB  - PURPOSE: The aim of this study was to assess the correlation between ocular
      surface changes and disease severity in patients with obstructive sleep apnea
      hypopnea syndrome (OSAHS). METHODS: Two hundred eighty patients with OSAHS were
      compared with respect to the presence of a floppy eyelid syndrome (FES), Ocular
      Surface Disease Index (OSDI) questionnaire, the corneal fluorescein staining
      stages, the Schirmer I test, and tear film break-up time (TBUT) values. RESULTS:
      Based on the apnea-hypopnea index, the presence of FES was detected at the
      following rates: 23.1 % in non-OSAHS group (A), 41.7 % in mild group (B), 66.7 %
      in moderate group (C), and 74.6 % in severe group (D); severe and moderate stage
      of FES was found in groups C and D and mild stage of FES in group B (p < 0.01).
      OSDI questionnaire values were as follows: group A, 12.57 +/- 17.64; group B,
      22.90 +/- 16.78; group C, 45.94 +/- 22.03; and group D, 56.68 +/- 22.85(p <
      0.01). Schirmer values were as follows: group A, 10.76 +/- 3.58 mm; group B, 9.83
      +/- 2.53 mm; group C, 7.73 +/- 2.42 mm; and group D, 6.97 +/- 2.15 mm (p < 0.01).
      The TBUT values were as follows: group A, 10.53 +/- 3.64 s; group B, 9.46 +/-
      2.40 s; group C, 7.29 +/- 2.13 s; and group D, 6.82 +/- 2.20 s (p < 0.01).
      Corneal staining scores are as follows: 0.26 +/- 0.60 in group A, 0.40 +/- 0.71
      in group B, 0.98 +/- 0.72 in group C, and 1.14 +/- 0.90 in group D, and the
      differences were statistically significant among the groups(p < 0.01).
      DISCUSSION: OSAHS, particularly the moderate and severe forms, is associated with
      low Schirmer and TBUT values and high scores in OSDI questionnaire and corneal
      staining pattern stage. The presence of FES is observed as a practically constant
      finding in OSAHS. If complaints such as burning, stinging, and itching which can
      be commonly observed in middle-aged patients are accompanied by FES, the patient
      should be evaluated for sleep disorders. We speculate that appropriate treatment
      of OSAHS may result in better control of these symptoms.

PMID- 22664771
TI  - Does uninsurance affect the health outcomes of the insured? Evidence from heart
      attack patients in California.
AB  - In this paper, I examine the impact of uninsured patients on the in-hospital
      mortality rate of insured heart attack patients. I employ panel data models using
      patient discharge and hospital financial data from California (1999-2006). My
      results indicate that uninsured patients have an economically significant effect
      that increases the mortality rate of insured heart attack patients. I show that
      these results are not driven by alternative explanations, including reverse
      causality, patient composition effects, sample selection or unobserved trends and
      that they are robust to a host of specification checks. The primary channel for
      the observed spillover effects is increased hospital uncompensated care costs.
      Although data limitations constrain my capacity to check how hospitals change
      their provision of care to insured heart attack patients in response to reduced
      revenues, the evidence I have suggests a modest increase in the quantity of
      cardiac services without a corresponding increase in hospital staff.

PMID- 22664772
TI  - The effects of cannabis use on physical and mental health.
AB  - This paper investigates whether cannabis use affects physical and mental health.
      To do so, information on prime aged individuals living in Amsterdam in 1994 is
      used. Dutch data offer a clear advantage in estimating the health impacts of
      cannabis use because the legal status of cannabis in the Netherlands ensures that
      estimates are free from confounding with the physical and psychological effects
      of engaging in a criminal activity. Accounting for selection into cannabis use
      and shared frailties in mental and physical health, the results suggest that
      cannabis use reduces the mental wellbeing of men and women and the physical
      wellbeing of men. Although statistically significant, the magnitude of the effect
      of using cannabis on mental and physical health is found to be small.

PMID- 22664773
TI  - Does smoking affect schooling? Evidence from teenagers in rural China.
AB  - Youth smoking can biologically reduce learning productivity. It can also reduce
      youths' expected returns to education and lower their motivation to go to school,
      where smoking is forbidden. Using rich household survey data from rural China,
      this study investigates the effect of youth smoking on educational outcomes.
      Youth smoking is clearly an endogenous variable; to obtain consistent estimates
      of its impact, we use counts of registered alcohol vendors and a food price index
      as instrumental variables. Since the variable that measures smoking behavior is
      censored for non-smoking adolescents, we implement a two-step estimation strategy
      to account for the censored nature of this endogenous regressor. The estimates
      indicate that smoking one cigarette per day during adolescence can lower
      students' scores on mathematics tests by about 0.08 standard deviations. However,
      we find no significant effect of youth smoking on either Chinese test scores or
      total years of schooling.

PMID- 22664774
TI  - Effect of job loss due to plant closure on mortality and hospitalization.
AB  - We investigate whether job loss due to plant closure causes an increased risk of
      (cause-specific) mortality and hospitalization for male workers having strong
      labour market attachment. We use administrative data: a panel of all persons in
      Denmark in the period 1980-2006, containing records on health and work status,
      and a link from workers to plants. We use propensity score weighting combined
      with non-parametric duration analysis. We find that job loss increases the risk
      of overall mortality and mortality caused by circulatory disease; of suicide and
      suicide attempts; and of death and hospitalization due to traffic accidents,
      alcohol-related disease, and mental illness.

PMID- 22664775
TI  - Application of "less is more" to low back pain.
AB  - An initiative of the National Physicians Alliance, the project titled "Promoting
      Good Stewardship in Clinical Practice," developed a list of the top 5 activities
      in primary care for which changes in practice could lead to higher-quality care
      and better use of finite clinical resources. One of the top 5 recommendations was
      "Don't do imaging for low back pain within the first 6 weeks unless red flags are
      present." This article presents data that support this recommendation. We
      selectively reviewed the literature, including recent reviews, guidelines, and
      commentaries, on the benefits and risks of routine imaging in low back pain. In
      particular, we searched PubMed for systematic reviews or meta-analyses published
      in the past 5 years. We also assessed the cost of spine imaging using data from
      the National Ambulatory Medical Care Survey. One high-quality systematic review
      and meta-analysis focused on clinical outcomes in patients with low back pain and
      found no clinically significant difference in pain or function between those who
      received immediate lumbar spine imaging vs usual care. Published data also
      document harms associated with early imaging for low back pain, including patient
      "labeling," unneeded follow-up tests for incidental findings, irradiation
      exposure, unnecessary surgery, and significant cost. Routine imaging should not
      be pursued in acute low back pain. Not imaging patients with acute low back pain
      will reduce harms and costs, without affecting clinical outcomes.

PMID- 22664776
TI  - Closing the serological gap: promising novel biomarkers for the early diagnosis
      of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by
      inflammation and damage of the joints affecting about 0.5% of the general
      population. Early treatment in RA is important as it can prevent disease
      progression and irreversible damage of the joints. Despite the high diagnostic
      value of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF),
      there is a strong demand for novel serological biomarkers to further improve the
      diagnosis of this abundant disease. During the last decades, several autoantigens
      have been described in RA including Ra33 (hnRNP A2), fibrinogen, fibronectin,
      alpha-enolase, type II collagen, immunoglobulin binding protein (BiP), annexins
      and viral citrullinated peptide (VCP) derived from Epstein Barr Virus-encoded
      protein (EBNA-2). More recent discoveries include antibodies to carbamylated
      antigens (anti-CarP), to peptidyl arginine deiminase type 4 (PAD4), to BRAF (v
      raf murine sarcoma viral oncogene homologue B1) and to 14 autoantigens identified
      by phage display technology. This review provides a current overview of novel
      biomarkers for RA and discusses their future potential to improve the diagnosis
      of the disease.

PMID- 22664777
TI  - Magnesium ascorbyl phosphate and coenzyme Q10 protect keratinocytes against UVA
      irradiation by suppressing glutathione depletion.
AB  - The aim of this study was to investigate whether magnesium ascorbyl phosphate
      (MAP) and coenzyme Q10 (CoQ10) can protect keratinocytes against ultraviolet
      (UV)A irradiation by increasing the levels of glutathione (GSH). The cell
      survival fraction was 89.9% when the keratinocytes were irradiated with UVA at a
      dose of 4 J/cm2. The cell survival fractions were 48.4, 9.1 and 4.8%, at doses of
      8, 16 and 32 J/cm2, respectively. MAP was added to the cells prior to UVA
      irradiation at a dose of 8 J/cm2 and then the cell viability was assayed. The
      cell survival fractions were 51.6, 55.5, 64.8 and 76.7%, when MAP was added at
      concentrations of 125, 250, 500 uM and 1 mM, respectively. The results showed
      that MAP is capable of protecting keratinocytes against UVA irradiation. The cell
      survival fractions were 77.2, 89.4 and 90.1%, when CoQ10 was added at
      concentrations of 2.5, 5 and 10 uM, respectively. The results revealed that CoQ10
      is capable of protecting keratinocytes against UVA irradiation. At the same time,
      the levels of GSH within cells were detected. The level of GSH within cells was
      0.3 mmol/g protein when the keratinocytes were irradiated with UVA at a dose of 8
      J/cm2. We measured the levels of GSH within the cells after MAP or CoQ10 was
      added prior to UVA irradiation at a dose of 8 J/cm2. The levels of GSH within the
      cells were 0.344, 0.388, 0.456 and 0.5 mmol/g protein, when MAP was added at
      concentrations of 125, 250, 500 uM and 1 mM, respectively. The levels of GSH
      within the cells were 0.328, 0.35 and 0.394 mmol/g protein, when CoQ10 was added
      at concentrations of 2.5, 5 and 10 uM, respectively. These results imply that MAP
      and CoQ10 can protect the keratinocytes against UVA irradiation, possibly via
      increasing the levels of GSH.

PMID- 22664778
TI  - Effects of general anesthetics on P2X4 receptors in a mouse microglial cell line.
AB  - The purinergic P2X4 receptors (P2X4Rs) of spinal microglia are upregulated after
      a peripheral nerve injury and play important roles in the pathogenesis of chronic
      pain. The effects of general anesthetics on chronic pain and the mechanisms are
      still unclear. The aim of this study is to examine the effects of general
      anesthetics on microglial P2X4Rs. Currents induced by ATP were recorded by the
      whole-cell clamp technique using a mouse microglial cell line (MG5). Isoflurane
      and sevoflurane, ketamine, thiopental, midazolam, and propofol were coapplied
      with ATP using the U-tube system or added to the external perfusate. ATP-induced
      two distinct types of current: P2X4R-mediated and P2X7R-mediated currents. P2X4R
      mediated currents were identified pharmacologically and isolated. Volatile
      anesthetics including sevoflurane and isoflurane and intravenous anesthetics
      including thiopental, ketamine, and midazolam had no effect at clinically
      relevant concentrations (n=5-8). Propofol showed a dual effect, potentiating at
      lower concentrations (0.3-3 uM) and inhibiting at higher concentrations (IC50 57
      uM). The maximum enhancement was observed at 1 uM propofol (143+/-5% of control,
      n=5). Propofol (1 uM) shifted the dose-response curve for the P2X4R currents to
      lower concentrations of ATP and increased the maximum amplitude. Propofol exerted
      dual actions on P2X4R-mediated currents at clinically relevant concentrations.
      This may suggest that the administration of propofol could affect the development
      of chronic pain through the modulation of microglial P2X4R responses.

PMID- 22664779
TI  - Nigral Tau pathology and striatal amyloid-beta deposition does not correlate with
      striatal dopamine deficit in Alzheimer's disease.
AB  - Extrapyramidal symptoms may appear in Alzheimer's disease (AD). In the present
      study, using morphometric immunohistochemistry in 34 cases with AD-related
      pathology, we evaluated whether nigral burden of tau pathology or striatal burden
      of amyloid-beta deposition correlates with dopamine transporter (DAT) expression
      in the striatum. Our observations show a lack of correlation between these
      variables and support the notion that lower striatal DAT expression in AD
      patients suggests concomitant nigral alpha-synuclein pathology. Extrapyramidal
      symptoms may have a complex background in AD.

PMID- 22664780
TI  - Biomarkers of neurodegeneration - not only Alzheimer's disease and not only
      cerebrospinal fluid: a guest-editor's introduction.

PMID- 22664781
TI  - Independent roles of monocyte chemoattractant protein-1, regulated on activation,
      normal T-cell expressed and secreted and fractalkine in the vulnerability of
      coronary atherosclerotic plaques.
AB  - BACKGROUND: Monocyte chemotactic factors contribute to the formation of
      atherosclerotic plaques. The present study aimed to elucidate the roles of
      monocyte chemoattractant protein-1 (MCP-1), Regulated on Activation, Normal T
      cell Expressed and Secreted (RANTES) and fractalkine on the vulnerability of
      atherosclerotic plaques in patients with acute myocardial infarction (AMI) or
      unstable angina pectoris (UAP). METHODS AND RESULTS: Sixty patients with AMI, 60
      patients with UAP, 60 patients with stable angina pectoris (SAP) and 40 patients
      without coronary heart disease comprised the study group. Quantitative coronary
      angiography and intravascular ultrasound (IVUS) were performed. Concentrations
      and mRNA expression levels of high-sensitivity C-reactive protein, MCP-1, RANTES
      and fractalkine were measured by ELISA and RT-PCR, respectively. IVUS found that
      51.3% of the AMI patients and 47.7% of the UAP patients had soft lipid plaques.
      Among the SAP patients, 52.4% had fibrous plaques and only 17.1% had soft
      plaques. AMI and UAP patients had larger plaque burden and vascular remodeling
      index than did the SAP patients (P<0.01). The averaged number of migrated
      monocytes was higher in AMI and UAP patients. Concentrations and mRNA expression
      levels of MCP-1, RANTES and fractalkine were significantly higher in AMI and UAP
      patients than in SAP patients (P<0.05-0.01). The plaque burden in UAP patients as
      measured with IVUS correlated well with monocytes chemotaxis (r=0.56, P<0.01).
      CONCLUSIONS: MCP-1, RANTES and fractalkine independently participate in the
      pathogenesis of plaque vulnerability and subsequent plaque rupture.  

PMID- 22664782
TI  - Differences in microparticle release in patients with acute coronary syndrome and
      stable angina.
AB  - BACKGROUND: Microparticles (MP) are vesicles released from activated or apoptotic
      cells. Endothelial MP (EMP) are derived from injured endothelium, platelet MP
      (PMP) from activated platelets, and Annexin V positive MP (AMP) from apoptotic
      endothelial cells. The aim was to assess the release of MP and its association
      with inflammation and atherosclerotic burden. METHODS AND RESULTS: AMP, EMP and
      PMP were measured on admission (Day 0) in 33 patients with stable angina (SA) and
      43 patients with acute coronary syndrome (ACS) undergoing percutaneous coronary
      interventions (PCI). In SA, peripheral artery disease (PAD) was assessed by
      ultrasound examination. In 30 of the 76 patients (20 ACS and 10 SA), MP, high
      sensitivity-C-reactive protein (hs-CRP), and troponin T (TnT) levels were also
      assessed 24h (Day 1) and 48 h (Day 2) after PCI. AMP, EMP, and PMP were higher in
      ACS than in SA (all P<0.01). In the SA group, AMP, PMP, and EMP were similar in
      patients with or without PAD. In the ACS group, AMP increased until Day 2
      (P=0.001), while EMP and PMP peaked on Day 1 (P<0.01) then decreased to baseline
      values. Day 2 AMP correlated with Day 2 TnT levels (r=0.43, P=0.01) while Day 1
      EMP and PMP correlated with Day 1 hs-CRP (r=0.37, P=0.04 and r=0.33, P=0.05;
      respectively). CONCLUSIONS: Higher MP levels were observed in ACS than in SA.
      Atherosclerotic burden did not affect MP levels in stable patients. 

PMID- 22664784
TI  - Left ventricular noncompaction: a diagnostically challenging cardiomyopathy.
AB  - Diagnosing left ventricular noncompaction (LVNC) cardiomyopathy is a challenge
      for the medical community because the condition shares morphologic features of
      hypertrophic and dilated cardiomyopathies. The uncertainty surrounding the
      diagnosis of LVNC is related to the lack of a "perfect diagnostic tool," such as
      a reproducible genetic marker. The diagnosis requires expertise in the broad
      spectrum of overlapping cardiomyopathies. The demarcation between LVNC and normal
      phenotypic variations is often indistinct. Echocardiography, used in routine
      clinical practice to identify the typical morphologic features of LVNC, can be
      overly sensitive and lack specificity with the presently defined measurements and
      ratios used to diagnose LVNC. The available diagnostic criteria show a propensity
      toward overdiagnosing LVNC. The complex clinical sequelae of atrial and
      ventricular arrhythmias, heart failure, thromboembolic events and sudden death
      associated with LVNC make a valid and reproducible diagnosis critical. The trend
      to using a morphologic/pathophysiologic, instead of a solely morphologic,
      approach holds promise in the quest for an accurate, reliable diagnosis of LVNC.
      We must understand the distinction between morphological findings and
      morphological findings with pathophysiology. Our future understanding of LVNC
      depends on an integration of cardiac morphology, physiology, pathophysiology and
      evolving genetics.

PMID- 22664785
TI  - Parkinson disease: Serotonin reuptake inhibitors for depression in PD.

PMID- 22664786
TI  - Spine surgery: Minimally invasive spinal surgery--does size matter?

PMID- 22664788
TI  - Multi-walled carbon nanotubes induce apoptosis via mitochondrial pathway and
      scavenger receptor.
AB  - We have demonstrated previously that the acid-treated multi-walled carbon
      nanotubes (aci-MWCNTs) and taurine functionalized MWCNTs (tau-MWCNTs) induced
      differential pulmonary toxicity in mice after instillation exposure. In order to
      compare differences of cytotoxicity between the aci- and tau-MWCNTs, RAW 264.7
      cells (a murine macrophage cell line) were chosen to be exposed to the aci- and
      tau-MWCNTs at concentrations of 0, 5, 20, 40, and 80MUg/ml for 12 or 24h
      respectively. The results showed that although the aci- and tau-MWCNTs induced
      only mild decrease in cell viability to RAW 264.7 cells, the two types of MWCNTs
      elicited significant increase in apoptosis and decreased ability in cellular
      phagocytosis. Moreover, by using the specific inhibitors, we found that the
      scavenger receptors (SR) and caspase-9 were actively involved in the apoptosis
      induced by the aci- and tau-MWCNTs. The taurine functionalized MWCNTs (tau
      MWCNTs) showed less cytotoxicity and apoptotic effect to RAW 264.7 cells than
      those of aci-MWCNTs. Taken together, the results indicated the important role of
      scavenger receptors and mitochondria in the apoptosis induced by MWCNTs.

PMID- 22664787
TI  - The immunology of acute stroke.
AB  - Recent clinical and experimental studies have highlighted a complex role for the
      immune system in the pathophysiological changes that occur after acute stroke.
      Sensors of the innate immune system such as Toll-like receptors, or effectors
      such as the lectin pathway of complement activation and innate immune cells, are
      activated by brain ischaemia and tissue damage, leading to amplification of the
      inflammatory cascade. Activation of the adaptive arm of the immune system,
      mediated by lymphocyte populations including T and B cells, regulatory T cells,
      and gammadeltaT cells, in response to stroke can lead to deleterious antigen
      specific autoreactive responses but can also have cytoprotective effects.
      Increased incidence of infections is observed after acute stroke, and might
      result from activation of long-distance feedback loops between the CNS and
      peripheral immune organs, which are thought to play a part in stroke-induced
      immunodepression. Ongoing clinical trials are investigating whether the
      preventive use of antibiotics improves functional outcome after stroke. This
      Review discusses the multifaceted role of the immune system in the
      pathophysiology of acute stroke.

PMID- 22664789
TI  - Oxidative damage in alveolar macrophages exposed to cigarette smoke extract and
      participation of nitric oxide in redox balance.
AB  - Nitric oxide (NO) acts in both pathological and biological processes. We
      investigated the role of NO in the regulation of cigarette smoke-induced
      oxidative stress in rat alveolar macrophages (RAM). RAM collected from Wistar
      rats were cultured in 5% concentration cigarette smoke extract (CSE) for 1h. RAM
      exposed to CSE were then co-incubated with L-NAME (LN), L-arginine (LA), N
      acetylcysteine (NAC) and both LN and NAC. RAM cultured only with medium was
      considered as control group. Biochemical analysis were performed to measure
      cellular metabolism (MTT), nitrite levels, superoxide dismutase (SOD) and
      glutathione peroxidase activities, reduced glutathione (GSH) and oxidized (GSSG),
      malondialdehyde and myeloperoxidase activity. During exposure to CSE, increased
      NO levels were not only associated with an increase of cell activation, but also
      affected MTT levels in RAM. CSE exposure resulted in significant redox imbalance
      in RAM. NAC administration affected SOD antioxidant profile regardless NO levels;
      however nitrite values were associated with GSH/GSSG ratio. In addition, lipid
      peroxidation appeared to be nitric-oxide dependent. Furthermore, the use of NAC
      significantly reduced the expression of NFkB normally observed in RAM exposed to
      CSE. The present results show that NO appeared to be involved in RAM activation,
      oxidative status maintenance and lipid peroxidation process during exposure to
      CSE.

PMID- 22664790
TI  - The androgenic anabolic steroid tetrahydrogestrinone produces dioxin-like effects
      via the aryl hydrocarbon receptor.
AB  - For a long time, athletes have used androgenic anabolic steroids (AASs) in an
      inappropriate and veiled manner with the aim of improving exercise performance or
      for cosmetic purposes. Abuse of AASs triggers adverse effects such as
      hepatocarcinogenesis, heart attacks, and aggressive behavior. However, AAS
      induced toxicity is not completely understood at the molecular level. In the
      present study, we showed, by performing a dioxin response element (DRE)
      luciferase reporter gene assay, that tetrahydrogestrinone (THG), a popular and
      potent androgen receptor agonist, has dioxin-like effects. In addition, we showed
      that THG increased cytochrome P-450 1A1 (CYP1A1) mRNA and protein levels, and
      enzyme activity. The gene encoding CYP1A1 is involved in phase 1 xenobiotic
      metabolism and a target gene of the aryl hydrocarbon receptor (AhR). Using the
      AhR antagonist CH-223191, we also examined whether the effects of THG on DRE
      activation depended on AhR. Our results suggest that synthetic anabolic steroids
      may have dioxin-like side effects that can disturb endocrine systems and may
      cause other side effects including cancer through AhR.

PMID- 22664792
TI  - Changing infant death rates: diagnostic shift, success story, or both?

PMID- 22664791
TI  - Trimodality therapy of esophagectomy plus neoadjuvant chemoradiotherapy improves
      the survival of clinical stage II/III esophageal squamous cell carcinoma
      patients.
AB  - The prognosis of advanced esophageal cancer patients is poor. Trimodality therapy
      of surgical resection plus neoadjuvant chemoradiotherapy (CRT) has been developed
      to improve survival through locoregional control, leading to prevention of
      micrometastasis. We investigated whether or not neoadjuvant CRT led to survival
      benefits in TNM stage II/III esophageal cancer patients. We retrospectively
      reviewed 62 patients with stage II or III esophageal squamous cell carcinoma
      (ESCC) treated with neoadjuvant CRT. All patients received esophagectomy 4-7
      weeks after CRT consisting of 40 Gy irradiation and chemotherapy (5-FU, 500
      mg/m2/day, days 1-5 and cisplatin, 10-20 mg/body, days 1-5). Clinical response
      and survival rates were analyzed using Kaplan-Meier methods, with p<0.05
      considered as significant. The clinical effect rate of CRT for both primary
      tumors and metastatic nodes was 82.3%. Operative and hospital mortality rates
      were 1.65 and 6.5%, respectively. The 3-year overall survival (OS) and disease
      free survival (DFS) rates were 52.6 and 49.2%, respectively. A significant
      difference was noted between stages II and III for both OS and DFS. The 5-year OS
      rates were 64.2% for stage II, 33.1% for stage III (T4 and non-T4) and 46.9% for
      stage III (non-T4 only) patients. The depth of tumor invasion (T3 vs. T4),
      resectability (R0 vs. R1, R2), lymph node metastasis (positive vs. negative), and
      the effect of CRT were proven to be independent prognostic factors for univariate
      analysis, with resectability and the effect of CRT for multivariate analysis.
      These data suggest that CRT in stage II/III (non-T4) ESCC patient contributed to
      tumor shrinkage, leading to higher resectability and longer survival. Neoadjuvant
      CRT appears to be a promising option for these patients.

PMID- 22664793
TI  - "Cobblestone" appearance of the ascending colon.

PMID- 22664794
TI  - Angiotensin II enhances epithelial-to-mesenchymal transition through the
      interaction between activated hepatic stellate cells and the stromal cell-derived
      factor-1/CXCR4 axis in intrahepatic cholangiocarcinoma.
AB  - We previously reported that hepatic stellate cells (HSCs) activated by
      angiotensin II (AngII) facilitate stromal fibrosis and tumor progression in
      intrahepatic cholangiocarcinoma (ICC). AngII has been known as a growth factor
      which can promote epithelial-to-mesenchymal transition (EMT) in renal epithelial
      cells, alveolar epithelial cells and peritoneal mesothelial cells. However, in
      the past, the relationship between AngII and stromal cell-derived factor-1 (SDF
      1) in the microenvironment around cancer and the role of AngII on EMT of cancer
      cells has not been reported in detail. SDF-1 and its specific receptor, CXCR4,
      are now receiving attention as a mechanism of cell progression and metastasis. In
      this study, we examined whether activated HSCs promote tumor fibrogenesis, tumor
      progression and distant metastasis by mediating EMT via the AngII/AngII type 1
      receptor (AT-1) and the SDF-1/CXCR4 axis. Two human ICC cell lines and a human
      HSC line, LI-90, express CXCR4. Significantly higher concentration of SDF-1alpha
      was released into the supernatant of LI-90 cells to which AngII had been added.
      SDF-1alpha increased the proliferative activity of HSCs and enhanced the
      activation of HSCs as a growth factor. Furthermore, addition of SDF-1alpha and
      AngII enhanced the increase of the migratory capability and vimentin expression,
      reduced E-cadherin expression, and translocated the expression of beta-catenin
      into the nucleus and cytoplasm in ICC cells. Co-culture with HSCs also enhanced
      the migratory capability of ICC cells. These findings suggest that SDF-1alpha,
      released from activated HSCs and AngII, play important roles in cancer
      progression, tumor fibrogenesis, and migration in autocrine and paracrine fashion
      by mediating EMT. Our mechanistic findings may provide pivotal insights into the
      molecular mechanism of the AngII and SDF-1alpha-initiated signaling pathway that
      regulates fibrogenesis in cancerous stroma, tumor progression and meta-stasis of
      tumor cells expressing AT-1 and CXCR4.

PMID- 22664795
TI  - Effect of early educational intervention on younger siblings: the Infant Health
      and Development Program.
AB  - OBJECT: To assess whether younger siblings of participants in an early
      (preschool) educational program would benefit in terms of developmental and
      educational outcomes. DESIGN: Assessment of a cohort of siblings of intervention
      participants at a mean age of 13.5 years. SETTING: The Infant Health and
      Development Program (IHDP), an 8-site randomized trial of 3 years of early
      education for premature low-birth-weight infants who were followed up through 18
      years of age. PARTICIPANTS: Siblings born within 5 years of the IHDP study
      participants. MAIN EXPOSURE: A sibling born no more than 5 years earlier who
      participated in the IHDP. MAIN OUTCOME MEASURES: Observed IQ; youth report of
      behavioral problems, their expectations of future success, and their relationship
      with their parents; and the caregiver's report on the youth's school progress and
      their expectations of the youth's educational attainment. RESULTS: Of 878 IHDP
      participants who were followed up, 466 (53.1%) had an eligible younger sibling,
      and 229 of those siblings (49.1%) agreed to participate. No differences were seen
      between the siblings of those who did and did not receive the IHDP intervention
      on any of the outcome measures. Adjusting for maternal race/ethnicity, age, and
      educational attainment at the birth of the study participant; study site; sex of
      the sibling; and losses to the cohort did not alter the results. CONCLUSION:
      Participation in an early educational program confers no apparent benefit on
      younger siblings in their early adolescent years.

PMID- 22664796
TI  - [How healthy is the lifestyle of adolescents in Germany?].
AB  - BACKGROUND: Studies on the health behaviour of adolescents mostly examine single
      health behaviour indicators in a separate manner for each one. However, health
      behaviours are not independently developed, but occur within a broader
      behavioural scheme acquired during socialisation. The aim of this study is to
      analyse the distribution of health-related behaviour patterns in adolescence by
      using a composite index made up of 6 single indicators allowing for
      sociodemographic and socioeconomic variables. METHODS: The data are derived from
      a subsample of the German Health Interview and Examination Survey for Children
      and Adolescents (KiGGS), carried out by the Robert Koch Institute between May
      2003 and May 2006 (age: 11-17 years, n=6 813). The creation of an additive
      healthy lifestyle index (HLI) is based upon data regarding smoking behaviour,
      body mass index, physical activity, use of electronic media, alcohol intake and
      fruit and vegetable consumption. The highest score of HLI is taken as a single
      indicator of a healthy lifestyle. Independent variables are socioeconomic status
      (SES) of the family of origin, school type and migration background. All analyses
      were done taking into account potential age and gender differences. RESULTS:
      Girls adhere more often to a recommended healthy lifestyle than boys (25.4% and
      18.7%, respectively). The proportion of adolescents adhering to all 6 HLI
      categories decreases with every year of life. Adolescents with a low SES and
      adolescents from secondary general schools ("Hauptschule") reach to a
      significantly lower extent the highest score of HLI than peers with a middle or
      high SES and adolescents attaining other types of schools. CONCLUSIONS: The
      results of the created HLI refer to latent potentials for prevention and specific
      target groups for health promotion measures.

PMID- 22664797
TI  - [The state of quality management implementation in ambulatory care nursing and
      inpatient nursing].
AB  - AIMS: The demands being made on quality assurance and quality management in
      ambulatory care nursing and inpatient nursing facilities continue to grow. As
      opposed to health-care facilities such as hospitals and rehabilitation centres,
      we know of no other empirical studies addressing the current state of affairs in
      quality management in nursing institutions. The aim of this investigation was, by
      means of a questionnaire, to analyse the current (as of spring 2011)
      dissemination of quality management and certification in nursing facilities using
      a random sample as representative as possible of in- and outpatient institutions.
      METHOD: To obtain our sample we compiled 800 inpatient and 800 outpatient
      facilities as a stratified random sample. Federal state, holder and, for
      inpatient facilities, the number of beds were used as stratification variables.
      24% of the questionnaires were returned, giving us information on 188 outpatient
      and 220 inpatient institutions. While the distribution in the sample of
      outpatient institutions is equivalent to the population distribution, we observed
      discrepancies in the inpatient facilities sample. As they do not seem to be
      related to any demonstrable bias, we assume that our data are sufficiently
      representative. RESULTS: 4 of 5 of the responding facilities claim to employ
      their own quality management system, however the degree to which the quality
      management mechanisms are actually in use is an estimated 75%. Almost 90% of all
      the facilities have a quality management representative who often possesses
      specific additional qualifications. Many relevant quality management instruments
      (i. e., nursing standards of care, questionnaires, quality circles) are used in
      75% of the responding institutions. Various factors in our data give the
      impression that quality management and certification efforts have made more
      progress in the inpatient facilities. Although 80% of the outpatient institutions
      claim to have a quality management system, only 32.1% of them admit to having
      already been (or be in current preparation to be) certified, a figure that was
      41.5% among the inpatient facilities. These percentages are smaller when one
      relies on information provided by the certifying institutions themselves rather
      on the nursing facilities. Most frequent is the certification according to the
      DIN EN ISO 9001 standard, since the care-specific certification procedures most
      widespread on the market enable facilities to combine a care-specific certificate
      with one according to DIN norms. CONCLUSION: Quality management has become very
      widespread in nursing facilities: every third institution claims to have been
      certified, and the trend to become certified has clearly intensified over the
      last few years. We observe overall very great acceptance of both internal quality
      management and external quality assurance. We suspect that the current use of
      quality management instruments in many nursing facilities will not fall behind
      such efforts in hospitals and rehabilitation centres.

PMID- 22664798
TI  - Randomized, multicenter, warfarin-controlled phase II study of edoxaban in
      Japanese patients with non-valvular atrial fibrillation.
AB  - BACKGROUND: Edoxaban is a once-daily (QD) oral, direct factor Xa inhibitor in
      clinical development for the prevention of stroke in patients with non-valvular
      atrial fibrillation (NVAF). The aim of this study was to evaluate the safety of
      edoxaban in Japanese patients with NVAF. METHODS AND RESULTS: A total of 536 NVAF
      patients (CHADS2 >=1) were randomized to receive double-blinded edoxaban 30, 45,
      or 60 mg QD or open-label warfarin (international normalized ratio [INR] 2.0-3.0
      for age <70 years; 1.6-2.6 for age >=70 years) for 12 weeks. The primary endpoint
      was the incidence of all bleeding events (major, clinically relevant non-major,
      and minor bleeds). Patients underwent CT and/or MRI to assess asymptomatic
      intracranial hemorrhage (ICH). Secondary endpoints included thromboembolic events
      and pharmacodynamic indices. The mean incidence of all bleeding events for
      edoxaban 30, 45, and 60mg, and warfarin was 18.5%, 22.4%, 27.7%, and 20.0%,
      respectively. There were no statistically significant differences among the
      edoxaban groups and no significant differences from the warfarin group. There
      were no asymptomatic ICH events in any group. One episode of cerebral infarction
      was observed in the edoxaban 45-mg group. Subgroup analysis suggested low body
      weight (<=60kg) was associated with higher bleeding risk. CONCLUSIONS: Edoxaban
      30, 45, and 60mg QD in patients with NVAF was associated with a numerical
      increase in all bleeding across the dose range, but this was not statistically
      significant, nor was any dose compared with warfarin.

PMID- 22664799
TI  - Beam-hardening correction for virtual monochromatic imaging of myocardial
      perfusion via fast-switching dual-kVp 64-slice computed tomography: a pilot study
      using a human heart specimen.
AB  - BACKGROUND: Investigate the effectiveness of beam-hardening (BH) correction using
      ECG-gated dual-kVp computed tomography (CT) for myocardial imaging. METHODS AND
      RESULTS: A human heart specimen and artificial descending aorta were scanned
      using both dual-kVp and single 120-kVp modes. The myocardial CT values at the
      anterior and posterobasal walls were 89.4+/-6.2 and 87.1+/-6.9 HU (P=0.59) for
      the 69-keV images, and 88.3+/-5.9 and 49.9+/-13.5 HU (P=0.002) for the 120-kVp
      images, respectively. CONCLUSIONS: Fast-switching dual-kVp technology is feasible
      for the correction of CT value deficits induced by BH that mimics perfusion
      defects.

PMID- 22664800
TI  - Newcomer joints old familiar faces.

PMID- 22664801
TI  - Inversion and crossover recombination contributions to the spacing between two
      functionally linked genes.
AB  - The roles of inversion and crossover recombination in determining the spacing
      between two functionally linked genes on an individual strand of DNA and the
      resulting genetic organization throughout the population is not well understood.
      We employ a computer simulation to look at the spacing between functionally
      linked genes after many generations of a population of haploid individuals, each
      with a single chromosome. Simulations show that inversion and crossover
      recombination combine to create four attractors in gene spacing. The two major
      attractors include one in which the linked genes are forced to be near each other
      and one in which the linked genes are forced to be separated by one third of the
      chromosome length. Multiplicative functional linkage between two linked genes
      also causes a decreased average spacing compared to additive and random
      functional linkage.

PMID- 22664802
TI  - Patterns and determinants of dyslipidaemia in 'Young' versus 'Not so Young'
      patients of coronary artery disease: a multicentric, randomised observational
      study in northern India.
AB  - AIMS: The aims of the study were to ascertain difference in lipid levels of
      'Young' onset of coronary artery disease (CAD) (<= 45 years) vs. 'Not so Young'
      onset of CAD (>= 55 years) among north Indians and also to investigate
      determinants of 'dyslipidaemia' in CAD patients. METHODS: This was a prospective,
      multicentric, randomised, observational study carried in eight centres of UP,
      India. All blood investigations were performed employing a central laboratory.
      RESULTS: Out of a total 435 patients studied, 218 were in the 'young group' (YG)
      and 235 were in the 'Not so Young Group' (NSYG). Dyslipidaemia was more common in
      YG as evident by significantly higher levels of total cholesterol, triglycerides,
      low- and very low-density lipoprotein cholesterol as compared to NSYG. Diabetes,
      hypertension, urban lifestyle, and family history of CAD were found to be
      important determinants of dyslipidaemia in YG. CONCLUSION: We conclude that lipid
      levels among north Indians are significantly higher in younger patients with CAD
      when compared with elderly.

PMID- 22664803
TI  - Metabolic cardiovascular risk factors worsen continuously across the spectrum of
      body mass index in Asian Indians.
AB  - OBJECTIVES: To determine relationship of body mass index (BMI) with multiple
      cardiovascular risk factors. METHODS: Population-based surveys were performed and
      1893 subjects aged 20-59 years evaluated. Data were collected using anthropometry
      and fasting glucose and lipid estimation. Statistical analyses were performed
      using curve fit and logistic regression. RESULTS: Body mass index was correlated
      significantly (Rho, R(2)) with weight (0.80, 0.64), waist (0.74, 0.55) and waist
      hip ratio (0.24, 0.06) (P < 0.05). Linear relationship was observed with systolic
      blood pressure (SBP) (0.39, 0.15), diastolic blood pressure (DBP) (0.29, 0.08),
      fasting glucose (0.13, 0.02), cholesterol (0.10, 0.01), high-density lipoprotein
      cholesterol (HDL-c) (-0.16, 0.03), and triglycerides (0.12, 0.01). Significant
      trends of risk factors with each increasing BMI unit (chi(2) test, P < 0.001)
      were observed for hypertension (HTN) (214.4), diabetes (29.5), metabolic syndrome
      (108.9), and low HDL-c (40.5), and weaker trends with hypercholesterolemia
      (20.6), and hypertriglyceridemia (9.6). There was exponential relationship of BMI
      with age- and sex-adjusted odds ratios for HTN, diabetes, and metabolic syndrome.
      CONCLUSION: Metabolic cardiovascular risk factors continuously worsen with
      increasing BMI.

PMID- 22664804
TI  - Early prediction of left ventricular systolic dysfunction in patients of
      asymptomatic chronic severe rheumatic mitral regurgitation using tissue Doppler
      and strain rate imaging.
AB  - AIMS: Identification of subclinical left ventricular (LV) dysfunction in patients
      with rheumatic mitral regurgitation (MR) facilitates optimal surgical results and
      better postoperative LV function. This study is designed to assess the role of
      tissue Doppler and strain rate (SR) imaging in early detection of LV systolic
      dysfunction in patients with asymptomatic chronic severe MR. METHODS AND RESULTS:
      Patients were studied under four groups. Group I: Normal subject (n = 25). Group
      II: Patients with chronic severe MR with ejection fraction (EF) > 60% and end
      systolic dimension (ESD) <= 40 mm (n=23). Group III: Patients with chronic severe
      MR with EF >= 60% and ESD 41-50 mm (n = 27). Group IV: Patients with chronic
      severe MR with EF < 60% with any ESDs (n = 25). With decrease in EF and increase
      in ESD there was decrease in systolic velocity and increased in precontraction
      time and contraction time was noted. The tissue Doppler systolic indices between
      groups were statistically significant P < 0.05 and showed significant correlation
      value r = 0.45 between groups. Strain (S) and SR significantly decreased with
      decrease in EF and increase in ESD P < 0.05, r = 0.45 between different groups.
      CONCLUSION: Our study showed significant correlation between tissue Doppler
      systolic indices and SR imaging with EF and ESD.

PMID- 22664805
TI  - Subclinical left ventricular systolic dysfunction in chronic mitral regurgitation
      and its potential impact on management: quo vadis?

PMID- 22664806
TI  - Diagnostic accuracy of 64-slice multidetector computed tomography in evaluation
      of post-coronary artery bypass grafts in correlation with invasive coronary
      angiography.
AB  - 64-slice multidetector computed tomography (MDCT) allows more reliable and non
      invasive evaluation of the coronary artery bypass grafts for occlusion or
      stenosis both in symptomatic and asymptomatic patients and also progression of
      disease in native coronary vessels.

PMID- 22664807
TI  - Diagnostic accuracy of coronary computed tomography angiography in patients post
      coronary artery bypass grafting.

PMID- 22664808
TI  - Validation of the GRACE score for prognosis in Indian patients with acute
      coronary syndromes.
AB  - AIM: To validate the global registry of acute coronary events (GRACE) score in
      acute coronary syndromes (ACS) patients and study its angiographic correlation.
      METHODS AND RESULTS: Two-hundred and thirty-five ACS patients were studied for
      the combined endpoint of all-cause in-hospital mortality and non-fatal
      infarction/reinfarction. We tested the predictive accuracy of the composite GRACE
      score using the receiver operating characteristics (ROC) curve. Lower systolic
      blood pressure (SBP) (odds ratio [OR] 7.93, P=0.005), ST-segment deviation (OR
      7.79, P=0.02) and cardiac biomarker positivity (OR > 6.52, P=0.01) were
      significantly associated with events. Serum creatinine > 1.4 mg/dL showed a trend
      towards statistical significance (OR 4.14, P=0.05), whereas age > 50 years (OR
      3.62, P=not significant [NS]) and Killips class 4 (OR 2.71, P=NS) showed good
      association. The best value for predicting events was a GRACE score of > 217 and
      these patients were more likely to have double/triple vessel disease (P =
      0.0009). The C statistic for the GRACE score was 0.75. CONCLUSION: Higher GRACE
      score predicts in-hospital events and more severe angiographic coronary artery
      disease (CAD).

PMID- 22664809
TI  - Composite risk scores for acute coronary syndromes.
AB  - There have been considerable advances in the management of acute coronary
      syndromes in the recent past. There are three risk scoring systems used for
      prognosticating these patients. An attempt is made in this article to discuss the
      pros and cons of the different risk scoring systems and their clinical utility.

PMID- 22664810
TI  - Systemic exposure of sirolimus after coronary stent implantation in patients with
      de novo coronary lesions: Supralimus-Core(r) pharmacokinetic study.
AB  - OBJECTIVES: This study was conducted to assess the systemic drug release and
      distribution of sirolimus-eluting coronary stents. METHODS: Twenty patients with
      coronary artery disease (CAD) were treated with 1, 2, or 3 a newly designed
      metallic stents. Blood samples were drawn at 14 time points to determine the
      pharmacokinetic of sirolimus. Whole blood concentrations of sirolimus were
      determined by using a sensitive validated high-performance liquid chromatography
      mass spectrometry/mass spectrometry method. RESULTS: Minimal measurable blood
      levels were detectable at 7 days. Across all dose levels, individual T(max)
      values ranged from 1.00 hour and 12.00 hours; individual C(max) ranged from 0.73
      ng/mL and 4.13 ng/mL. CONCLUSION: This study confirms the limited exposure of the
      systemic circulation of the eluted drug with the use of the Supralimus-Core(r)
      Sirolimus-Eluting Coronary Stent System (Sahajanand Medical Technologies Pvt.
      Ltd., Surat, India). In this study, sirolimus concentration in systemic
      circulation is to be safe, well-tolerated and short-lived.

PMID- 22664811
TI  - Prehypertension in young females, where do they stand?
AB  - BACKGROUND: To determine the prevalence of prehypertension in young females and
      its correlation to various parameters like body mass index (BMI), waist hip ratio
      (WHR), waist circumference (WC) and family history, and blood pressure (BP)
      response to exercise stress testing. METHODS: One hundred and fifty apparently
      healthy females of age group 18-25-years were randomly selected from the student
      population of Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha, after
      satisfying all the inclusion criteria and written informed consent. Along with
      all the anthropometric parameters BMI, WHR, WC and family history of hypertension
      (HTN) and/or diabetes, resting BP, and BP response to exercise stress testing
      were measured in the study. RESULTS: Amongst 150 subjects, 63 (42%) subjects were
      normotensive and 87 (58%) were prehypertensive. Body mass index, WHR, WC and
      family history of HTN were significantly higher in prehypertensive group.
      Prehypertensive group also had an exaggerated BP response to exercise stress
      testing and higher BP during recovery. CONCLUSION: Prevalence of prehypertension
      was found to be high in females, also there was a strong correlation between
      prehypertension and BMI, WHR and WC suggesting a positive correlation between
      obesity and prehypertension. Prehypertensive group also showed an exaggerated BP
      response to exercise stress testing.

PMID- 22664812
TI  - Visceral adiposity in young patients with coronary artery disease-a case control
      study.
AB  - AIMS: Central obesity is associated with an increased cardiovascular risk. We
      carried out a hospital based case control study in young patients with coronary
      artery disease (CAD) to assess the importance of visceral fat METHODS: Coronary
      artery disease was established by coronary angiogram in all cases. Controls were
      age- and sex-matched subjects with normal coronary angiogram. Computed tomography
      scan performed at the level of the umbilicus to measure subcutaneous and visceral
      fat area (VFA). RESULTS: Cases and controls were well matched in height, weight,
      and body mass index (BMI). Visceral fat area was significantly higher (122.58 +/-
      37.59 vs. 88.4 +/- 36.95 cm(2); P=0.003) in cases whereas subcutaneous fat area
      was similar in cases and controls. Visceral fat area was an excellent predictor
      of cardiovascular risk (area under receiver operating characteristics curve 0.915
      cm(2)). Visceral fat area correlated with BMI, waist hip ratio, blood sugar,
      triglycerides, and C-reactive protein significantly. CONCLUSION: Visceral
      adiposity is associated with an increased risk of CAD and it correlated with
      anthropometric, metabolic, and inflammatory markers.

PMID- 22664813
TI  - Levels of cathepsins in acute myocardial infarction.
AB  - AIMS/OBJECTIVE: Over expression of matrix degrading enzymes have been implicated
      in plaque destabilisation and rupture. Cathepsins associated with extracellular
      matrix breakdown make them intriguing suspects. The aim of the study was to
      analyse peripheral levels of cathepsin B and cathepsin K and their inhibitor
      cystatin C during acute myocardial infarction (AMI). MATERIALS AND METHODS: Study
      population included AMI patients at acute event (AMI group, n=48), stable angina
      patients (stable angina group n = 17), and healthy individuals (Control group,
      n=31). Cathepsin B, cathepsin K, cystatin C, and matrix metalloproteinases (MMP)
      9 were analysed by enzyme-linked immunosorbent assay (ELISA) method. RESULTS:
      Cathepsin B (45.9%) and cathepsin K (92.31%) at acute event of myocardial
      infarction (AMI group) increased (P=0.001) while cystatin C decreased marginally
      (12.5%) as compared to controls. Stable angina group, demonstrated only marginal
      reduction in all the parameters studied as compared to controls. CONCLUSION:
      Cathepsin B and cathepsin K can be further evaluated as biomarkers in identifying
      high-risk individuals for AMI.

PMID- 22664814
TI  - A study of clinical presentation and delays in management of acute myocardial
      infarction in community.
AB  - To assess the medico social demographics of acute myocardial infarction (AMI) in
      our community we studied 609 patients presenting between January 2008 to December
      2008 with a detailed questionnaire in four centres of UP. Medical attention was
      sought late (> 6 hours) in 316 (51.6%), thrombolysis was obtained in 45.2% (275)
      and presentation was atypical in 16.3% (99). 36.2% (221) had pre-monitory
      symptoms of which 68% (150) ignored the same while of 32% (71) who did seek
      medical attention 47.9% (37) were brushed away as non-cardiac in origin. 20.3%
      (46/226) of hypertension, 23.2% (43/185) of diabetes and 83.4% (91/109) of
      hyperlipidaemia was diagnosed post event. We conclude that at least half of
      patients with AMI do not get definitive therapy, at least one in 10 patients do
      not have the classical symptoms, reasonable proportion are unaware of their risk
      factors, and a good majority have pre-monitory symptoms which get overlooked.

PMID- 22664815
TI  - Correlation between NT proBNP and left ventricular ejection fraction in elderly
      patients presenting to emergency department with dyspnoea.
AB  - OBJECTIVE: Shortness of breath is a common complaint for which the elderly seek
      medical attention in the emergency department (ED). Differentiating cardiac from
      respiratory causes of dyspnoea in this population is quite a challenge. N
      Terminal pro brain-natriuretic-peptide (NT proBNP) has been studied extensively
      as a biomarker of left ventricular (LV) failure. METHODS: The NT proBNP was
      measured in 100 patients above 60 years of age who presented to the ED with
      shortness of breath. The level was compared with echocardiographic findings to
      assess correlation with ejection fraction (EF). RESULTS: The NT proBNP values
      increased significantly as the functional severity of heart failure (HF)
      increased (P < 0.001). The mean NT proBNP level was 1503.33 pg/mL. Patients with
      respiratory causes of dyspnoea had a mean NT proBNP level of 309.28 pg/mL with
      normal LV function. CONCLUSION: The NT proBNP levels had a good correlation with
      worsening LVEF.

PMID- 22664783
TI  - Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation - the J
      ROCKET AF study -.
AB  - BACKGROUND: The global ROCKET AF study evaluated once-daily rivaroxaban vs.
      warfarin for stroke and systemic embolism prevention in patients with atrial
      fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan
      specific rivaroxaban dose with warfarin administered according to Japanese
      guidelines in Japanese patients with AF. METHODS AND RESULTS: J-ROCKET AF was a
      prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with
      non-valvular AF at increased risk for stroke were randomized to receive 15 mg
      once-daily rivaroxaban or warfarin dose-adjusted according to Japanese
      guidelines. The primary objective was to determine non-inferiority of rivaroxaban
      against warfarin for the principal safety outcome of major and non-major
      clinically relevant bleeding, in the on-treatment safety population. The primary
      efficacy endpoint was the composite of stroke and systemic embolism. Non
      inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal
      safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per
      year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence
      interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates
      were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a
      reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin
      (HR, 0.49; P=0.050). CONCLUSIONS: J-ROCKET AF demonstrated the safety of a Japan
      specific rivaroxaban dose and supports bridging the global ROCKET AF results into
      Japanese clinical practice.

PMID- 22664816
TI  - Uterine artery embolisation.
AB  - PURPOSE OF STUDY: Fibroids are commonest benign tumour of the uterus. It presents
      with bleeding per vagina in most of the cases. Surgical treatment consists of
      myomectomy or hysterectomy with or without salpingo oophrectomy, with its
      inherent morbidity, prolonged hospital stay and psychosocial problems. Surgery is
      not the best option especially in unmarried and nullipara. MATERIALS AND METHODS:
      Thirty-five patients were subjected to uterine artery embolisation (UAE). Mean
      age was 35.51 +/- 7.36 years. Two patients were suffering from advanced carcinoma
      of cervix, 32 had fibroid of uterus, one had endometriosis. Three patients were
      unmarried, three did not have any issue, three had associated haemodynamically
      significant cardiac disorders, one had polycystic renal disease, and one had
      hypernephroma. Four patients had multiple fibroids. The UAE was done through
      contralateral femoral artery puncture, bilaterally, with the help of Judkin's
      right coronary catheter. Ultrasound was repeated after 3 months. RESULTS: The UAE
      was successful in all patients. Mean procedural time was 75 minutes. Hospital
      stay was 1 day only. Bleeding stopped in all 35 patients. One patient had
      recurrence of bleeding after 2 months and underwent surgery. Fibroids disappeared
      in eight patients, decreased in size by > 75% in 11 patients, and by 50-75% in
      six patients. Five patients did not report back with ultrasound. Two patients had
      normal delivery after UAE. CONCLUSION: Uterine artery embolisation is effective
      therapy to stop uterine bleeding. It is effective in controlling the symptoms in
      uterine fibroids and also decreases the size of fibroids. Hospital stay is only 1
      day.

PMID- 22664817
TI  - Effects of music on systolic blood pressure, diastolic blood pressure, and heart
      rate: a meta-analysis.
AB  - There are a handful of studies that have been done investigating the effect of
      music on various vital signs, namely systolic blood pressure (SBP), diastolic
      blood pressure (DBP), and heart rate (HR). Many studies have also assessed
      effects of music on self-reported anxiety level, attributing some degree of music
      induced anxiety relief to the beneficial impacts of music on vital signs. Several
      randomised studies have shown varying effects of music on these vital parameters
      and so a meta-analysis was done to compare the effect of music on them. The fixed
      effects model was used as studies were homogenous. A two-sided alpha error < 0.05
      was considered to be statistically significant. Compared to those who did not
      receive music therapy, those who did receive music therapy had a significantly
      greater decrease in SBP before and after (difference in means, -2.629, confidence
      interval (CI), -3.914 to -1.344, P < 0.001), a significantly greater decrease in
      DBP (difference in means, -1.112, CI, -1.692 to -0.532, P < 0.001), and a
      significantly greater decrease in HR (difference in means, -3.422, CI, -5.032 to 
      1.812, P < 0.001).

PMID- 22664818
TI  - Impact of preload changes on positive and negative left ventricular dP/dt and
      systolic time intervals: preload changes on left ventricular function.
AB  - AIM/OBJECTIVES: Previous work has shown that the electromechanical activation
      time (EMAT) is prolonged in patients with abnormally low left ventricular (LV)
      dP/dt. In the present study, we investigated whether EMAT was responsive to rapid
      changes in LV systolic function induced by abrupt increases in LV preload.
      METHODS AND RESULTS: A total of 116 patients were assessed before and after LV
      angiography with a bolus injection of 40 mL of non-ionic contrast dye. Left
      ventricular end-diastolic pressure (LVEDP) increased from 18 +/- 7 mmHg to 20 +/-
      8 mmHg (P < 0.01). In patients with a baseline dP/dt < 1500 mmHg/sec, dP/dt
      increased from 1098 +/- 213 mmHg/sec to 1146 +/-306 mmHg/sec (P=0.02) and EMAT
      decreased from 106 +/- 29 ms to 103 +/-18 ms (P=0.02). In patients with a
      baseline dP/dt > 1500 mmHg/sec, dP/dt decreased from 1894 +/- 368 mmHg/sec to
      1762 +/- 403 mmHg/sec (P=0.01) and EMAT increased from 88 +/- 13 ms to 93 +/- 16
      ms (P=0.02). Changes in negative dP/dt were similar to changes in dP/dt.
      CONCLUSION: Electromechanical activation time is a non-invasively measured
      parameter that allows accurate and rapid detection of changes in LV
      contractility.

PMID- 22664820
TI  - Three dimensional epicardial mapping and ablation of recurrent non-ischaemic
      ventricular tachycardia.
AB  - Radiofrequency ablation is a therapeutic option for recurrent ventricular
      tachycardia (VT) in both ischaemic and non-ischaemic subsets. Usually this is
      attempted by mapping endocardially; however, in some situations epicardial
      approach may be needed to access the VT circuit. We report two cases in which
      epicardial approach was used to successfully ablate the VT, when endocardial
      ablation was ineffective.

PMID- 22664819
TI  - Hypertension in Bangladesh: a review.
AB  - Hypertension (HTN) is an increasingly important medical and public health
      problem. In Bangladesh, approximately 20% of adult and 40-65% of elderly people
      suffer from HTN. High incidence of metabolic syndrome, and lifestyle-related
      factors like obesity, high salt intake, and less physical activity may play
      important role in the pathophysiology of HTN. The association of angiotensin
      converting enzyme (ACE) gene polymorphism and low birth weight with blood
      pressure has been studied inadequately. Studies have found relationship between
      mass arsenic poisoning and HTN. Hypovitaminosis D presumably plays role in the
      aetiopathogenesis of HTN in Bangladeshi population. South Asians appear to
      respond to antihypertensive therapy in a similar manner to the Whites. The latest
      National Institute for Health and Clinical Excellence guideline advocates a
      calcium-channel blocker as step 1 antihypertensive treatment to people aged > 55
      years and an ACE inhibitor or a low-cost angiotensin-II receptor blocker for the
      younger people. Calcium-channel blockers and beta-blockers have been found to be
      the most commonly prescribed antihypertensive drugs in Bangladesh. Non-adherence
      to the standard guidelines and irrational drug prescribing are likely to be
      important. On the other hand, non-adherence to antihypertensive treatment is
      quite high. At the advent of the new millennium, we are really unaware of our
      real situation. Large-scale, preferably, nation-wide survey and clinical research
      are needed to explore the different aspects of HTN in Bangladesh.

PMID- 22664821
TI  - Markedly varying PR intervals during second degree atrioventricular block:
      possible mechanisms.
AB  - A case of second degree atrioventricular block following mitral valve replacement
      is presented during which varying PR intervals with sudden marked increase in PR
      interval in consecutive beats was seen. The electrocardiogram is discussed and
      various hypotheses to explain the possible electrophysiological mechanism are
      presented.

PMID- 22664822
TI  - Ruptured type B aortic dissection masquerading as massive left pleural effusion.

PMID- 22664823
TI  - Surgical care of international patients with congenital heart disease in India.

PMID- 22664824
TI  - Anaplastic lymphoma kinase-directed therapy in inflammatory myofibroblastic
      tumors.
AB  - PURPOSE OF REVIEW: Inflammatory myofibroblastic tumors (IMTs) are indolent
      mesenchymal neoplasms associated with a small risk of aggressive behavior and
      metastasis. Surgery is the mainstay of treatment and until recently there have
      been limited effective treatment options for unresectable disease. This review
      describes the identification of anaplastic lymphoma kinase (ALK) fusion genes in
      approximately 50% of IMTs and the role of ALK inhibition in the treatment of this
      disease. RECENT FINDINGS: A recent phase I dose-escalation trial of the selective
      MET/ALK inhibitor crizotinib showed a long-term partial response in a patient
      with IMT carrying an ALK translocation but not in a patient with ALK-negative
      disease. Emergence of resistance to crizotinib occurs approximately 5-8 months
      after initiation of therapy and has been shown to be driven by different
      mechanisms. Multiple second-generation ALK inhibitors are currently being
      investigated in the preclinical and clinical trial setting. SUMMARY: ALK-directed
      therapy has emerged as a highly effective treatment option for a subset of
      patients with IMT and pulmonary adenocarcinoma. A number of additional
      malignancies, including rhabdomyosarcoma, neuroblastoma, anaplastic large cell
      lymphoma, renal cell carcinoma, and inflammatory breast cancer, have been shown
      to activate ALK expression by means of ALK fusion proteins, ALK mutations, or
      increased ALK copy number. Development of more selective ALK inhibitors, which
      can overcome emergent crizotinib resistance mutations, as well as development of
      combination treatments with drugs targeting compensatory pathways, will be key to
      achieving therapeutic success in targeting this potent and prevalent oncogenic
      driver.

PMID- 22664825
TI  - Current world literature.

PMID- 22664827
TI  - Providers are still the first line of defense against smoking.

PMID- 22664828
TI  - Amisulpride in the treatment of fibromyalgia: an uncontrolled study.
AB  - Some antipsychotics, including amisulpride, have shown to be effective in the
      treatment of various painful conditions, lessening pain as well as symptoms of
      anxiety and/or depression. In this open-label, 12-week study, we explored the
      efficacy and tolerability of amisulpride in patients with fibromyalgia. We
      recruited 40 patients, 1 male and 39 females, aged 46.2 +/- 6.8 years, who met
      the ACR criteria for fibromyalgia and had a score equal to or greater than 4 in
      the pain severity item of the Fibromyalgia Impact Questionnaire (FIQ).
      Amisulpride was added to their current treatment regimen at an initial dose of 25
      mg/day and titrated according to the clinical response and tolerability (mean
      final dose, 87.5 +/- 41.3 mg/day). In the intent-to-treat analysis (i.e., all
      recruited patients), using a baseline-observation-carried-forward approach, the
      mean score in the FIQ decreased from 75.7 +/- 10.6 to 73.2 +/- 15.4, but this
      change was not statistically significant. Pain severity, as measured with the
      visual analogue scale from the FIQ, remained unchanged. Nonsignificant
      improvements were observed in depressive or anxiety symptoms using the Beck
      Depression Inventory and the State-Trait Anxiety Inventory, respectively. Twenty
      six patients either withdrew from the study, mainly due to adverse reactions, or
      were lost to follow-up (n = 11, 27.5 %, for each category). Despite its promising
      results in some chronic painful conditions and in a related illness, such as
      chronic fatigue syndrome, amisulpride does not seem to provide any benefit to
      patients with fibromyalgia. Amisulpride was poorly tolerated by our participants.

PMID- 22664829
TI  - Are the top 5 recommendations enough to improve clinical practice?: comment on
      "Application of 'less is more' to low back pain".

PMID- 22664830
TI  - Carbon monoxide (CO) and hydrogen sulfide (H(2)S) in hypoxic sensing by the
      carotid body.
AB  - Carotid bodies are sensory organs for monitoring arterial blood oxygen (O(2))
      levels, and the ensuing reflexes maintain cardio-respiratory homeostasis during
      hypoxia. This article provides a brief update of the role of carbon monoxide (CO)
      and hydrogen sulfide (H(2)S) in hypoxic sensing by the carotid body. Glomus
      cells, the primary site of O(2) sensing in the carotid body express heme
      oxygenase-2 (HO-2), a CO catalyzing enzyme. HO-2 is a heme containing enzyme and
      has high affinity for O(2). Hypoxia inhibits HO-2 activity and reduces CO
      generation. Pharmacological and genetic approaches suggest that CO inhibits
      carotid body sensory activity. Stimulation of carotid body activity by hypoxia
      may reflect reduced formation of CO. Glomus cells also express cystathionine
      gamma-lyase (CSE), an H(2)S generating enzyme. Exogenous application of H(2)S
      donors, like hypoxia, stimulate the carotid body activity and CSE knockout mice
      exhibit severely impaired sensory excitation by hypoxia, suggesting that CSE
      catalyzed H(2)S is an excitatory gas messenger. Hypoxia increases H(2)S
      generation in the carotid body, and this response was attenuated or absent in CSE
      knockout mice. HO inhibitor increased and CO donor inhibited H(2)S generation. It
      is proposed that carotid body response to hypoxia requires interactions between
      HO-2-CO and CSE-H(2)S systems.

PMID- 22664831
TI  - Radiofrequency ablation for colorectal liver metastases: prognostic factors in
      non-surgical candidates.
AB  - PURPOSE: To determine prognostic factors in patients with colorectal liver
      metastases who were not surgical candidates and received liver radiofrequency
      (RF) ablation. MATERIALS AND METHODS: RF ablation was done for 141 colorectal
      liver metastases in 84 patients. There were 63 (75.0 %, 63/84) males and 21 (25.0
      %, 21/84) females, with a mean age of 64.6 +/- 10.3. The mean maximum tumor
      diameter was 2.3 +/- 1.4 cm (range 0.5-9.0 cm). Extrahepatic metastases were
      associated at the time of liver RF ablation in 23 patients (27.4 %, 23/84), and
      12 (14.3 %, 12/84) had lung metastases considered controllable by planned lung RF
      ablation. Prognostic factors were evaluated by univariate and multivariate
      analyses. RESULTS: There was no procedure-related mortality. The 1-, 3-, and 5
      year overall survival rates were 90.6 % (95 %CI, 83.9-97.2 %), 44.9 % (95 %CI,
      31.8-57.9 %), and 20.8 % (95 %CI, 7.3-34.3 %), respectively, with a median
      survival of 34.9 months. The univariate analysis showed that tumor diameter
      larger than 3 cm, tumor multiplicity, uncontrollable extrahepatic disease, and
      previous chemotherapy history were significantly worse prognostic factors. The
      former three factors remained significant for worse prognosis in the multivariate
      Cox model. Extrahepatic disease was not a prognostic factor when it could be
      controlled. CONCLUSION: Tumor size and number, and uncontrollable extrahepatic
      metastases were significant prognostic factors.

PMID- 22664832
TI  - Tropism between hepatic and pulmonary metastases in colorectal cancers.
AB  - In metastatic colorectal cancers, tumor cells are disseminated prior to surgical
      resection of the primary tumor but remain dormant until proper colonization
      mechanisms are activated. To identify the colonization mechanisms of the
      metastatic tumors, we conducted a pairwise comparison between primary colorectal
      cancers and metastatic tumors (n=12 pairs), including six hepatic pairs and six
      pulmonary pairs. The mRNA levels of 224 genes previously reported to be
      associated with metastasis, cytokines and angiogenesis were quantitatively
      determined by PCR arrays. Among them, 27 genes were duplicated or triplicated to
      show consistent expression. Unsupervised hierarchical clustering of the Ct values
      of metastasis-related genes revealed that liver metastases were indistinguishable
      from primary colorectal cancers (n=5/6), whereas lung metastases were highly
      diversified from one another and from the primary tumors (n=6/6). Cytokines and
      receptor gene expression array data also confirmed the divergence of pulmonary
      metastases from primary colorectal cancers (n=6/6). Heat map analyses of DeltaCt
      values of the metastasis-related genes identified a 17-gene tropism signature
      that was sufficient not only to distinguish liver and the lung metastases, but
      also reconstituted the clustering of primary tumors with the hepatic metastases
      (n=17/18). In this pilot experiment, pulmonary metastases were significantly
      diverged from hepatic metastases that were indistinguishable from primary
      colorectal cancers. Further genomic and clinical studies are in progress to
      evaluate the potential of the tropism signature as a therapeutic target to
      inhibit the colonization of metastatic colorectal cancers.

PMID- 22664833
TI  - Experimental arthritis: Stability of T(REG) cells induced ex vivo boosts
      prospects for cellular therapies.

PMID- 22664834
TI  - The advent of biosimilar therapies in rheumatology--"O brave new world".
AB  - Patents for many key biological agents will soon expire. Third-party companies
      are, therefore, in the process of developing their own versions, termed
      biosimilar agents, of these innovator products. However, manufacture of
      biosimilar agents is complicated by the requirement for their production in
      biological systems, small variations in which can influence the structure,
      activity and metabolism of the biosimilar product. The development of biosimilar
      therapies for the treatment of patients with rheumatic diseases could potentially
      result in substantial cost savings for patients and health care providers, and
      consequently, increased availability of effective therapies. However, legislation
      that regulates the manufacture, registration and approval of biosimilar therapies
      varies considerably between different countries. In addition, major safety and
      efficacy concerns must be addressed before a rheumatologist can routinely
      substitute an innovator pharmaceutical with a biosimilar product.

PMID- 22664835
TI  - Complement in the immunopathogenesis of rheumatic disease.
AB  - The complement system has vital protective functions as a humoral component of
      the innate immune system and also through interactions with the adaptive immune
      system; however, when inappropriately activated or regulated, complement can
      cause inflammation and organ damage, and such processes are involved in the
      pathogenesis of many inflammatory conditions, not least rheumatic diseases.
      Furthermore, states of complement deficiency can predispose not only to
      infections, but also to autoimmune disorders, including rheumatic diseases such
      as systemic lupus erythematosus. In this Review, the mechanisms behind the
      pathogenic activities of complement in rheumatic diseases are discussed.
      Potential approaches to therapeutic intervention that focus on regulating
      complement activities in these disorders are also considered.

PMID- 22664837
TI  - Pain: Pain therapy for 'hot' joints: what works?

PMID- 22664836
TI  - Bone turnover markers: use in osteoporosis.
AB  - Biochemical markers of bone turnover (bone turnover markers, BTMs) can be used to
      study changes in bone remodelling in osteoporosis. Investigators and clinicians
      should be aware of the appropriate sample collection and storage conditions for
      optimum measurements of these markers. Improvements in the variability of BTM
      measurements have resulted from the development of assays for automated
      analysers, and from international consensus regarding their use. Appropriate
      reference intervals should be used for the optimum interpretation of results.
      BTMs can provide information that is useful for the management of patients with
      osteoporosis, for both the initial clinical assessment and for guiding and
      monitoring of treatment. BTMs are clinically useful to determine possible causes
      of secondary osteoporosis by identifying patients with high bone turnover and
      rapid bone loss. In the follow-up of treatment response, BTM levels respond
      rapidly to both anabolic and antiresorptive treatments. BTM changes can also be
      used for understanding the mechanism of action of drugs in development and
      identifying the correct dose; they are also potentially useful as surrogate
      biomarkers for fracture.

PMID- 22664838
TI  - Isolation and culture of rat embryonic neural cells: a quick protocol.
AB  - We are describing a quick method to dissociate and culture hippocampal or
      cortical neurons from E15-17 rat embryos. The procedure can be applied
      successfully to the isolation of mouse and human primary neurons and neural
      progenitors. Dissociated neurons are maintained in serum-free medium up to
      several weeks. These cultures can be used for nucleofection, immunocytochemistry,
      nucleic acids preparation, as well as electrophysiology. Older neuronal cultures
      can also be transfected with a good efficiency rate by lentiviral transduction
      and, less efficiently, with calcium phosphate or lipid-based methods such as
      lipofectamine.

PMID- 22664840
TI  - The role of industry interactions with the American College of Gastroenterology.

PMID- 22664841
TI  - IBS patients' willingness to take risks with medications.
AB  - OBJECTIVES: We explored irritable bowel syndrome (IBS) patients' impulsivity and
      risk-taking behavior and their willingness to take medication risks. METHODS: A
      validated questionnaire assessed the illness experience of IBS patients. A
      standard gamble evaluated respondents' willingness to take medication risks.
      RESULTS: IBS patients with severe symptoms were more willing to take significant
      medication risks than those with mild or moderate symptoms. Impulsivity scores
      were not associated with an increased likelihood of taking medication risks. Age,
      gender, and years of IBS symptoms were not associated with medication risk-taking
      behavior. IBS patients reported they would accept a median 1% risk of sudden
      death for a 99% chance of cure for their symptoms using a hypothetical
      medication. CONCLUSIONS: IBS patients are willing to take significant medication
      risks to cure their symptoms. To counsel patients effectively, physicians must
      determine and understand IBS patients' risk aversion.

PMID- 22664842
TI  - Images of the month: Gastrointestinal Kaposi's sarcoma.

PMID- 22664847
TI  - Editorial: Novel imaging for endoscopic evaluation of gastroesophageal reflux
      disease: seeing is believing.
AB  - One of the challenges to the effective management of gastroesophageal reflux
      disease (GERD) is the multiple pathophysiological etiologies that contribute to
      this symptom complex. The majority of patients with GERD have no visible
      abnormalities during standard endoscopic examination, and this subgroup of
      patients, defined as having non-erosive reflux disease (NERD), has a low response
      rate to acid suppression therapy with proton pump inhibitors. With advances in
      endoscopic imaging technology, it may soon be possible to better define subtle
      esophagus lesions in these patients, which may help identify those that will
      respond to acid suppressive therapy. In order for these technologies to have a
      role in the evaluation and management of patients with GERD, several criteria
      must be met. To date, electronic chromoendoscopy and confocal laser
      endomicroscopy appear to hold the most promise based on the existing data and
      reproducibility of the identified esophageal abnormalities. However, there
      continues to be a need for high-quality research, as not a single imaging
      technology has been shown to predict therapeutic response rates in NERD patients.

PMID- 22664848
TI  - Editorial: From the acute infection to the chronic disorder "Don't worry it's
      just a viral gastroenteritis".
AB  - Postinfectious functional gastrointestinal disorders (PI-FGID) have become a
      category in the general FGID classification. Bacterial PI-FGID has been well
      documented in several studies and meta-analysis. Increased risk does not appear
      to be confined to bacterial gastroenteritis (GE), also protozoan and helminth
      infections are sometimes followed by PI-FGID. In this issue of the journal,
      Zanini et al. provides evidence that Norovirus GE also leads to the development
      of PI-irritable bowel syndrome in a substantial proportion of patients.

PMID- 22664849
TI  - Oral or IV iron in inflammatory bowel disease.

PMID- 22664851
TI  - The MMAS-8, a screening tool for determining nonadherent behavior, should not be
      dismissed in IBD.

PMID- 22664853
TI  - Recovery of a "Jackhammer esophagus" after the treatment of an eosinophilic
      esophagitis.

PMID- 22664855
TI  - Localized primary ileal lymphoma found on colonoscopic examination.

PMID- 22664856
TI  - Metastasis squared: colon cancer spread to the preexisting skeletal metastasis of
      thyroid carcinoma.

PMID- 22664857
TI  - An unusual cause of hypertriglyceridemic acute pancreatitis.

PMID- 22664859
TI  - Destructive discovertebral degenerative disease of the lumbar spine.
AB  - The uncommon variant of degenerative hip joint disease, termed rapidly
      progressive osteoarthritis, and highlighted by severe joint space loss and
      osteochondral disintegration, is well established. We present a similar unusual
      subset in the lumbar spine termed destructive discovertebral degenerative disease
      (DDDD) with radiological features of vertebral malalignment, severe disc
      resorption, and "bone sand" formation secondary to vertebral fragmentation. Co
      existing metabolic bone disease is likely to promote the development of DDDD of
      the lumbar spine, which presents with back pain and sciatica due to nerve root
      compression by the "bone sand" in the epidural space. MRI and CT play a
      complimentary role in making the diagnosis.

PMID- 22664860
TI  - Pericruciate fat pad of the knee: anatomy and pericruciate fat pad inflammation:
      cadaveric and clinical study emphasizing MR imaging.
AB  - OBJECTIVE: The pericruciate fat pad is located in the intercondylar fossa,
      intimate with the cruciate ligaments. With MR imaging, signal abnormality of the
      pericruciate fat pad has been observed in patients with posterior knee pain. The
      purpose of this study was to describe the anatomy of the pericruciate fat pad in
      cadaveric specimens and to document the clinical spectrum of pericruciate fat pad
      inflammation. MATERIALS AND METHODS: Twelve cadaveric knees underwent MR imaging
      with T1 and T2 multiplanar images. Cadaveric sections were then prepared for
      macroscopic evaluation, with additional histologic analysis performed in four
      cases. MR images in seventeen patients (ten males, seven females; average age,
      31.5 years; age range, 19-57 years) involved in intensive sporting activity and
      with posterior knee pain were reviewed. RESULTS: MR images in cadaveric specimens
      showed a fat pad that was located above and between the cruciate ligaments, near
      their attachment sites in the inner portion of the femoral condyles, within the
      intercondylar fossa. Fatty tissue covered by a thin layer of synovial membrane
      was confirmed at histology. Seventeen patients with posterior knee pain and
      without gross cartilage, meniscal, or ligamentous abnormalities all revealed an
      increased signal in this fat pad in fluid-sensitive fat-suppressed images, mainly
      in the sagittal and axial planes. In eight cases, enhancement of this fat pad was
      demonstrated following intravenous gadolinium administration. CONCLUSIONS: The
      pericruciate fat pad is a structure located in the intercondylar fossa, intimate
      with both the anterior and posterior cruciate ligaments. Inflammatory changes in
      this fat pad may be found in patients, especially athletes with posterior knee
      pain.

PMID- 22664861
TI  - Randomized controlled trial of slow vs rapid enteral feeding advancements on the
      clinical outcomes of preterm infants with birth weight 750-1250 g.
AB  - OBJECTIVE: To evaluate the effect of slow vs rapid rates of advancement of
      enteral feed volumes on the clinical outcomes in preterm infants with 750-1250 g
      birth weight. STUDY DESIGN: A total of 92 stable neonates 750-1250 g and
      gestational age <32 weeks were randomly allocated to enteral feeding advancement
      of 20 mL/kg/d (n = 46) or 30 mL/kg/d (n = 46). The primary outcome was days to
      reach full enteral feeding, defined as 180 mL/kg/d. Secondary outcomes included
      rates of necrotizing enterocolitis (NEC) and culture-proven sepsis, days of
      parenteral nutrition (PN), length of hospital stay, and growth end points.
      RESULTS: Neonates in the rapid-feeding advancement group achieved full enteral
      volume of feedings earlier than the slower advancement group. They received
      significantly fewer days of PN, exhibited a shorter time to regain birth weight,
      and had a shorter duration of hospital stay. The incidence of NEC and the number
      of episodes of feeding intolerance were not significantly different between the
      groups, whereas the incidence of culture-proven late-onset sepsis was
      significantly less in infants receiving a rapid feeding advancement. Excluding
      infants who were small for gestational age at birth, the incidence of
      extrauterine growth restriction was significantly reduced in the rapid
      advancement group at 28 days and at hospital discharge. CONCLUSION: Rapid enteral
      feeding advancements in 750-1250 g birth weight infants reduce the time to reach
      full enteral feeding and the use of PN administration. Rapid-advancement enteral
      feed also decreases extrauterine growth restriction with improved short-term
      outcomes for these high-risk infants.

PMID- 22664862
TI  - Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the
      proliferation and invasion of human prostate cancer cells in vitro through
      suppression of Ras activation.
AB  - Phosphoprotein associated with glycosphingolipid microdomains 1 (PAG) is an
      important negative regulator of immune signaling in T lymphocytes. However, newly
      emerging evidence has indicated that PAG may play important roles in tumor cells.
      Our previously reported cDNA microarray experiments identified PAG as a gene down
      regulated in the high metastatic potential prostate cancer cell line PC-3M-1E8.
      In this study, we investigated the role of PAG in the proliferation, invasion and
      metastasis of prostate cancer cells and the underlying mechanisms. We confirmed
      that the expression of PAG at both the mRNA and protein levels was low in PC-3M
      1E8 and DU145 cells compared to low metastatic potential prostate cancer cells PC
      3M-2B4. In addition, we demonstrated that the reintroduction of PAG to PC-3M-1E8
      and DU145 cells led to reduced proliferation through cell cycle arrest, decreased
      anchorage-independent growth and reduced invasion ability of tumor cells in
      vitro. This is the first report demonstrating that PAG inhibits the proliferation
      and invasion potential of prostate cancer cells via the interaction with RasGAP
      to recruit RasGAP to the cell membrane, where RasGAP hydrolyzes GTP to GDP,
      reduces the level of activated Ras, and ultimately suppresses the activation of
      ERK1/2, cyclin D1 and other effectors of the Ras signaling pathway.
      Morphologically, we observed that PAG could diminish the formation of pseudopodia
      on the cell surface and redistribute the intracellular F-actin in PC-3M-1E8
      cells, which directly leads to the decreased invasion and metastasis potential of
      tumor cells. Taken together, these results suggest that PAG acts to inhibit the
      development and metastasis of prostate cancers and represents a novel therapeutic
      target for prostate cancer.

PMID- 22664863
TI  - Hypertension and obesity: epidemiology, mechanisms and clinical approach.
AB  - Obesity-related hypertension in pediatric patients is becoming more prevalent
      around the world as a consequence of the childhood obesity epidemic. Hypertension
      and the metabolic abnormalities associated with obesity will significantly
      increase the health risks for these children as they grow into adulthood. The
      pathophysiology of obesity-related hypertension is complex, and multiple
      potential mechanisms likely contribute to the development of higher blood
      pressure in obese children. These include hyperinsulinemia, activation of the
      renin-angiotensin-aldosterone system, stimulation of the sympathetic nervous
      system, abnormalities in adipokines such as leptin, direct effects of perinephric
      fat on the renal parenchyma, and cytokines acting at the vascular endothelial
      level. As in any child with elevated blood pressure, diagnostic evaluation should
      focus on confirmation of hypertension, determine if an underlying cause can be
      identified and whether hypertensive target organ damage is present. Therapy
      should begin with lifestyle modifications, but will often need to include one or
      more antihypertensive medications.

PMID- 22664865
TI  - Congenital Rubella Syndrome.

PMID- 22664864
TI  - Primer on renal transplantation.
AB  - Renal transplantation transforms chronically ill children with end stage renal
      disease (ESRD) into near normal resulting in improvement in nutrition, growth,
      neurodevelopment and quality of life, and is the goal of therapy. However, the
      benefits of transplantation come at a price of life-long treatment with
      immunosuppressive medications, increased risk of infections and malignancy.
      Children younger than 10 y of age have the best, and adolescents have the worst 5
      y graft survival likely due to non-adherence with medications in the adolescents.
      Long-term complications include ongoing issues related to chronic kidney disease
      (CKD) and cardiovascular morbidity and mortality contributing to graft loss and
      shortened life expectancy, thus limiting the success of organ transplantation.
      Therefore, appropriate management of CKD and cardiovascular issues should be
      integral to the care of pediatric transplant patients. The other ongoing
      challenges include organ shortage, prevention and treatment of late acute
      rejections and chronic graft dysfunction, discovering reliable noninvasive immune
      monitoring tools, improving adherence, psychosocial rehabilitation, and the
      elusive goal of tolerance.

PMID- 22664866
TI  - Genome-wide screening for methylation-silenced genes in colorectal cancer.
AB  - Identification of methylation-silenced genes in colorectal cancer (CRC) is of
      great importance. We employed oligonucleotide microarrays to identify differences
      in global gene expression of five CRC cell lines (HCT116, RKO, Colo320, SW480 and
      HT29) that were analyzed before and after treatment with 5-aza-2'-deoxycitidine.
      Selected candidates were subjected to methylation-specific PCR and real-time
      quantitative reverse transcription-PCR using 15 CRC cell lines and 23 paired
      tumor and normal samples from CRC patients. After 5-aza-2'-deoxycitidine
      treatment, 139 genes were re-expressed in all 5 CRC cell lines collectively with
      a fold change of more than 1.5 in at least one cell line. These genes include
      known methylated and silenced genes in CRC. After applying study selection
      criteria we identified 20 candidates. The GADD45B and THSD1 genes were selected
      for further analysis. Among 15 colon cancer cell lines, methylation was only
      identified in THSD1 (27%). THSD1 methylation was subsequently investigated in 23
      colorectal tumors and methylation was detected in 9% of the analyzed samples; the
      observed promoter hypermethylation was cancer-specific. THSD1 mRNA down
      regulation was observed in tumor tissues. This genome-wide screening led to the
      identification of genes putatively affected by methylation in CRC. The THSD1 gene
      may play a role in the tumorigenesis of CRC.

PMID- 22664867
TI  - Impact of stent platform of paclitaxel-eluting stents: assessment of neointimal
      distribution on optical coherence tomography.
AB  - BACKGROUND: The Taxus ExpressTM paclitaxel-eluting stent (Express-PES) and Taxus
      LiberteTM PES (Liberte-PES) have identical drugs, drug doses, and polymers, but
      different stent platforms. The Liberte-PES platform has thinner struts,
      specifically designed for more uniform drug elution. METHODS AND RESULTS: Fifty
      four patients who underwent 6-month follow-up optical coherence tomography (OCT)
      after Express-PES (n=27) or Liberte-PES (n=27) implantation were enrolled.
      Longitudinal and circumferential uniformity of neointimal distribution was
      evaluated in 3-D by computing mean neointimal thickness (NIT) within 360 equally
      spaced radial sectors for every 1-mm cross-section. After stenting, intravascular
      ultrasound showed that Liberte-PES had a significantly smaller maximum angle
      between adjacent struts, with a tendency toward a lower incidence of % length of
      the segment with maximum angle >90 degrees  than Express-PES. Liberte-PES had a
      significantly thinner mean NIT than the Express-PES with comparable frequency of
      uncovered struts. Longitudinal and circumferential absolute variation of NIT
      expressed by standard deviation of NIT from each sector was significantly smaller
      for Liberte-PES than for Express-PES. Liberte-PES had a tendency toward a
      decreased incidence of thrombus and peri-strut low-intensity areas (findings
      suggestive of delayed arterial healing), compared to Express-PES. CONCLUSIONS:
      Stent design and thickness appeared to affect neointima suppression of PES. The
      stent platform of the Liberte-PES may offer greater and more homogeneous
      reduction of neointimal proliferation spatially across the full length of the
      PES.

PMID- 22664868
TI  - Endothelial Gab1 deletion accelerates angiotensin II-dependent vascular
      inflammation and atherosclerosis in apolipoprotein E knockout mice.
AB  - BACKGROUND: Docking protein Grb2-associated binder 1 (Gab1) has critical roles in
      signal transduction of various growth factors, cytokines, and numerous other
      molecules. Our previous reports show that Gab1 is essential for postnatal
      angiogenesis through the analysis of endothelium-specific Gab1 knockout
      (Gab1ECKO) mice. However, the role of Gab1 in atherosclerosis remains unknown.
      The aim of the present study was to elucidate the role of endothelial Gab1 in
      vascular inflammation and atherosclerosis. METHODS AND RESULTS: We intercrossed
      Gab1ECKO mice with apolipoprotein E (ApoE) knockout (ApoEKO) mice. Six-month-old
      male ApoEKO/Gab1ECKO and littermate control (ApoEKO) mice were treated with
      angiotensin II (AngII) via an osmotic infusion mini-pump. After AngII treatment,
      ApoEKO/Gab1ECKO mice showed significantly enhanced atherosclerosis and aneurysm
      formation compared with control mice. The production of proinflammatory cytokines
      in the aorta was significantly enhanced in ApoEKO/Gab1ECKO mice compared with
      control mice. Furthermore, the expression levels of Kruppel-like factor (KLF) 2
      (KLF2) and KLF4, key transcription factors for endothelial homeostasis, were
      significantly reduced in the aortic endothelium of ApoEKO/Gab1ECKO mice compared
      with those of control mice. Consistently, both vascular cell adhesion molecule-1
      expression and macrophage infiltration on the aortic walls were enhanced in
      ApoEKO/Gab1ECKO mice compared with control mice. CONCLUSIONS: Collectively,
      endothelial Gab1 deletion accelerates AngII-dependent vascular inflammation and
      atherosclerosis on ApoE-null background presumably in association with
      downregulation of KLF2 and KLF4.

PMID- 22664869
TI  - Differing requirements for CCR4, E-selectin, and alpha4beta1 for the migration of
      memory CD4 and activated T cells to dermal inflammation.
AB  - CCR4 on T cells is suggested to mediate skin homing in mice. Our objective was to
      determine the interaction of CCR4, E-selectin ligand (ESL), and alpha(4)beta(1)
      on memory and activated T cells in recruitment to dermal inflammation. mAbs to
      rat CCR4 were developed. CCR4 was on 5-21% of memory CD4 cells, and 20% were also
      ESL(+). Anti-TCR-activated CD4 and CD8 cells were 40-55% CCR4(+), and ~75% of
      both CCR4(+) and CCR4(-) cells were ESL(+). CCR4(+) memory CD4 cells migrated 4-
      to 7-fold more to dermal inflammation induced by IFN-gamma, TNF, TLR agonists,
      and delayed-type hypersensitivity than CCR4(-) cells. CCR4(+) activated CD4 cells
      migrated only 5-50% more than CCR4(-) cells to these sites. E-selectin blockade
      inhibited ~60% of CCR4(+) activated CD4 cell migration but was less effective on
      memory cells where alpha(4)beta(1) was more important. Anti-alpha(4)beta(1) also
      inhibited CCR4(-) activated CD4 cells more than CCR4(+) cells. Anti-E-selectin
      reduced activated CD8 more than CD4 cell migration. These findings modify our
      understanding of CCR4, ESL, alpha(4)beta(1), and dermal tropism. There is no
      strict relationship between CCR4 and ESL for skin homing of CD4 cells, because
      the activation state and inflammatory stimulus are critical determinants. Dermal
      homing memory CD4 cells express CCR4 and depend more on alpha(4)beta(1) than ESL.
      Activated CD4 cells do not require CCR4, but CCR4(+) cells are more dependent on
      ESL than on alpha(4)beta(1), and CCR4(-) cells preferentially use
      alpha(4)beta(1). The differentiation from activated to memory CD4 cells increases
      the dependence on CCR4 for skin homing and decreases the requirement for ESL.

PMID- 22664870
TI  - Role of M2b macrophages in the acceleration of bacterial translocation and
      subsequent sepsis in mice exposed to whole body [137Cs] gamma-irradiation.
AB  - The influence of whole-body gamma-irradiation on the antibacterial host defense
      against Enterococcus faecalis translocation was investigated. Mice irradiated
      with or without 5 Gy [(137)Cs] gamma-rays were orally infected with 10(6)
      CFU/mouse E. faecalis. The pathogen was detected in the mesenteric lymph nodes
      (MLNs) of irradiated mice 1-4 d postinfection, whereas E. faecalis was not
      isolated from MLNs of normal mice. All irradiated mice died within 5 d of
      infection, whereas no mortality was shown in normal mice infected with the
      pathogen. Irradiated mice inoculated with normal mouse MLN macrophages (M) were
      shown to be resistant against the infection, although the same mice inoculated
      with irradiated mouse MLNM (I-MLNM) died postinfection. I-MLNM were identified as
      IL-10(+)IL-12(-)CCL1(+)LIGHT(+) M (M2bM) and were shown to be inhibitory on M
      conversion from resident M to IL-10(-)IL-12(+)M (M1M). M2bM were demonstrated in
      MLNs of mice 10-35 d after gamma-irradiation. M1M were not induced by E. faecalis
      Ag in cultures of I-MLNM, whereas normal mouse MLNM were converted to M1M in
      response to the Ag stimulation. After treatment with CCL1 antisense
      oligodeoxynucleotides, M2bM disappeared in MLNs of irradiated mice, and M1M were
      generated in MLNs of these mice following E. faecalis stimulation. These results
      indicate that M2bM presented in the I-MLNM populations were responsible for the
      impaired resistance of mice irradiated with gamma-rays to bacterial translocation
      and subsequent sepsis. E. faecalis translocation and subsequent sepsis may be
      controlled immunologically by the intervention of M2bM present in MLNs.

PMID- 22664871
TI  - Crystal structure of human RANKL complexed with its decoy receptor
      osteoprotegerin.
AB  - Receptor activator of NF-kappaB ligand (RANKL), its signaling receptor RANK, and
      its decoy receptor osteoprotegerin (OPG) constitute a molecular triad that is
      critical in regulating bone remodeling, and also plays multiple roles in the
      immune system. OPG binds RANKL directly to block its interaction with RANK. In
      this article, we report the 2.7-A crystal structure of human RANKL trimer in
      complex with the N-terminal fragment of human OPG containing four cysteine-rich
      TNFR homologous domains (OPG-CRD). The structure shows that RANKL trimer uses
      three equivalent grooves between two neighboring monomers to interact with three
      OPG-CRD monomers symmetrically. A loop from the CRD3 domain of OPG-CRD inserts
      into the shallow groove of RANKL, providing the major binding determinant that is
      further confirmed by affinity measurement and osteoclast differentiation assay.
      These results, together with a previously reported mouse RANKL/RANK complex
      structure, reveal that OPG exerts its decoy receptor function by directly
      blocking the accessibilities of important interacting residues of RANKL for RANK
      recognition. Structural comparison with TRAIL/death receptor 5 complex also
      reveals structural basis for the cross-reactivity of OPG to TRAIL.

PMID- 22664873
TI  - The indispensable role of CCR5 for in vivo suppressor function of tumor-derived
      CD103+ effector/memory regulatory T cells.
AB  - CD103 is a marker for identification of effector/memory regulatory T cells
      (Tregs). CD103(+) Tregs are potent suppressors of tissue inflammation in several
      infectious diseases, autoimmune diseases, and cancers. However, the underlying
      mechanisms for this potent suppression ability remain unclear. The current study
      was designed to clarify this issue. Unexpectedly, we found both CD103(+) and
      CD103(-) Tregs had similar suppression capacity in vitro. We then chose a murine
      tumor model for investigation of the in vivo behavior of these Tregs. The
      suppression ability in vivo against the anti-tumor ability of CD8(+) T cells was
      restricted to CD103(+) Tregs although both Tregs had equal in vitro suppression
      ability. In addition, CD103(+) Tregs expressed significantly higher levels of
      CCR5 than those of CD103(-) Tregs and accumulated more in tumors than did CD103(
      ) Tregs. Furthermore, blockade of CCR5 signaling, either by CCR5(-/-)CD103(+)
      Tregs or by CCL5 knockdown tumor, could reduce the migration of CD103(+) Tregs
      into tumors and impair their in vivo suppression ability. In conclusion, these
      results indicate that the potent in vivo suppression ability of CD103(+) Tregs is
      due to the tissue-migration ability through CCR5 expression.

PMID- 22664874
TI  - Tumor-associated microglia/macrophages enhance the invasion of glioma stem-like
      cells via TGF-beta1 signaling pathway.
AB  - The invasion of malignant glioma cells into the surrounding normal brain tissues
      is crucial for causing the poor outcome of this tumor type. Recent studies
      suggest that glioma stem-like cells (GSLCs) mediate tumor invasion. However, it
      is not clear whether microenvironment factors, such as tumor-associated
      microglia/macrophages (TAM/Ms), also play important roles in promoting GSLC
      invasion. In this study, we found that in primary human gliomas and orthotopical
      transplanted syngeneic glioma, the number of TAM/Ms at the invasive front was
      correlated with the presence of CD133(+) GSLCs, and these TAM/Ms produced high
      levels of TGF-beta1. CD133(+) GSLCs isolated from murine transplanted gliomas
      exhibited higher invasive potential after being cocultured with TAM/Ms, and the
      invasiveness was inhibited by neutralization of TGF-beta1. We also found that
      human glioma-derived CD133(+) GSLCs became more invasive upon treatment with TGF
      beta1. In addition, compared with CD133(-) committed tumor cells, CD133(+) GSLCs
      expressed higher levels of type II TGF-beta receptor (TGFBR2) mRNA and protein,
      and downregulation of TGFBR2 with short hairpin RNA inhibited the invasiveness of
      GSLCs. Mechanism studies revealed that TGF-beta1 released by TAM/Ms promoted the
      expression of MMP-9 by GSLCs, and TGFBR2 knockdown reduced the invasiveness of
      these cells in vivo. These results demonstrate that TAM/Ms enhance the
      invasiveness of CD133(+) GSLCs via the release of TGF-beta1, which increases the
      production of MMP-9 by GSLCs. Therefore, the TGF-beta1 signaling pathway is a
      potential therapeutic target for limiting the invasiveness of GSLCs.

PMID- 22664875
TI  - Understanding the alphabet soup of mechanical ventilation.
AB  - Invasive mechanical ventilation has evolved from a fairly simplistic, basic
      machine with just a few knobs into an exceedingly complicated, microprocessor
      based life support system. This article sorts out the "alphabet soup" concerning
      mechanical ventilation and focuses on invasive procedures.

PMID- 22664876
TI  - Preoperative intra-aortic balloon pumping in high-risk cardiac surgery patients.
AB  - Intra-aortic balloon pumping increases myocardial oxygen supply and decreases
      myocardial oxygen demand by inflation and deflation of the balloon. This leads to
      increased perfusion of the coronary arteries during diastole. This technology has
      been used for critically ill cardiac patients for more than 30 years. The
      literature suggests that preoperative use of an intra-aortic balloon pump can be
      effective in high-risk coronary artery bypass grafting patients. Preoperative
      benefits of this technology may yield positive outcomes in terms of hemodynamic
      effect, decreased length of stay in both the intensive care unit and the
      hospital, and the reduction of complications. However, the intra-aortic balloon
      pump must be used with a profound understanding of proper mechanism and function,
      monitoring, and observation for potential complications. This requires excellent
      critical care nursing management.

PMID- 22664872
TI  - The role of sphingosine-1-phosphate transporter Spns2 in immune system function.
AB  - Sphingosine-1-phosphate (S1P) is lipid messenger involved in the regulation of
      embryonic development, immune system functions, and many other physiological
      processes. However, the mechanisms of S1P transport across cellular membranes
      remain poorly understood, with several ATP-binding cassette family members and
      the spinster 2 (Spns2) member of the major facilitator superfamily known to
      mediate S1P transport in cell culture. Spns2 was also shown to control S1P
      activities in zebrafish in vivo and to play a critical role in zebrafish
      cardiovascular development. However, the in vivo roles of Spns2 in mammals and
      its involvement in the different S1P-dependent physiological processes have not
      been investigated. In this study, we characterized Spns2-null mouse line carrying
      the Spns2(tm1a(KOMP)Wtsi) allele (Spns2(tm1a)). The Spns2(tm1a/tm1a) animals were
      viable, indicating a divergence in Spns2 function from its zebrafish ortholog.
      However, the immunological phenotype of the Spns2(tm1a/tm1a) mice closely
      mimicked the phenotypes of partial S1P deficiency and impaired S1P-dependent
      lymphocyte trafficking, with a depletion of lymphocytes in circulation, an
      increase in mature single-positive T cells in the thymus, and a selective
      reduction in mature B cells in the spleen and bone marrow. Spns2 activity in the
      nonhematopoietic cells was critical for normal lymphocyte development and
      localization. Overall, Spns2(tm1a/tm1a) resulted in impaired humoral immune
      responses to immunization. This study thus demonstrated a physiological role for
      Spns2 in mammalian immune system functions but not in cardiovascular development.
      Other components of the S1P signaling network are investigated as drug targets
      for immunosuppressive therapy, but the selective action of Spns2 may present an
      advantage in this regard.

PMID- 22664877
TI  - Donation after cardiac death: ethical dilemmas and implications for advanced
      practice nurses.
AB  - Donation after cardiac death has always presented ethical concerns among health
      care providers. As advanced practice nurses and critical care nurses, it is our
      responsibility to ensure that health care providers and families are educated
      about the process and that we remain advocates for the potential donors. This
      article reviews the donation after cardiac death process, provides a donation
      after cardiac death hypothetical case report and its outcome, and addresses the
      ethical concerns associated with donation after cardiac death from both
      opponents' and proponents' points of view. It will also discuss the benefits of
      obtaining a palliative care consult and the roles of the advanced practice nurse
      in the care of the potential donor.

PMID- 22664879
TI  - Interdisciplinary education on discussing end-of-life care.
AB  - The interactions and observations of residents speaking with patients and family
      members about end-of-life decisions indicated a need for more empathy. Nursing
      and medical students have been called to learn and work together so they can work
      more effectively. A review of the evidence on interdisciplinary education of
      residents concerning end-of-life care and communicating with patients and their
      family members was the inspiration for this study. This article applies evidence
      related to interdisciplinary education in critical care settings. This pilot
      project was a collaboration of medical education between a critical care service
      in a public hospital and baccalaureate nursing students assisting family members
      in making end-of-life decisions. As nursing students, we were able to effectively
      present content on end-of-life decision making to medical residents.

PMID- 22664885
TI  - Cultural and linguistic validation of the Italian version of the intensive care
      delirium screening checklist.
AB  - The purposes of this study were to identify the most suitable rating scale for
      the diagnosis of delirium in the Italian setting and to develop and validate an
      Italian version of a delirium screening checklist. The findings are reported.

PMID- 22664886
TI  - Reactions to patient death: the lived experience of critical care nurses.
AB  - A qualitative study using phenomenological descriptive design was conducted to
      explore critical care nurses' experiences with patient death. Several themes
      emerged as a result of this study: coping, personal distress, emotional
      disconnect, and inevitable death. Understanding critical care nurses' reactions
      to patient death may help to improve the care provided to critically ill dying
      patients and their families and to meet the needs of the nurses who care for
      them.

PMID- 22664892
TI  - A closing word: do not resuscitate versus allow natural death and should we
      change our approach.

PMID- 22664893
TI  - Single incision vs. conventional multiport laparoscopic cholecystectomy: a
      comparison of two approaches.
AB  - BACKGROUND AND AIMS: Laparoscopic techniques are rapidly evolving and trends
      towards a more minimally invasive approach have led to the introduction of single
      incision and natural orifice laparoscopic surgery. The aim of this study was to
      compare the outcomes of single-incision laparoscopic cholecystectomy (SILC) to
      conventional multiport laparoscopic cholecystectomy (MPLC). We compared intra
      operative complications, operative time, postoperative complications, pain score,
      readmission rate and conversion to open amongst both groups. METHODS: A
      retrospective review of data of patients who underwent laparoscopic
      cholecystectomy between May 2009 and November 2011 was performed. All procedures
      were performed by a single surgeon. RESULTS: A total of 184 patients underwent
      laparoscopic cholecystectomy. 76 patients from MPLC were excluded from comparison
      based on exclusion criteria. The remaining 62 patients in MPLC and 45 patients in
      the SILC group were compared. The two groups were similar with respect to
      patients' demographics and American Society of Anaesthesiology grades. The median
      operative time for SILC was 75 min (range 42-120) compared to 60 min (range 26
      117) in MPLC (p = 0.02). There was no conversion to open procedure. One patient
      in SILC group was converted to MPLC and two patients required a second port
      insertion. Postoperative pain-score and length of hospital stay were comparable
      in both groups. One patient in each group had minor bleeding from gall bladder
      bed controlled with diathermy. CONCLUSION: SILC is a safe and feasible approach
      in selected patients. There was no difference in complication rate amongst the
      two approaches with a longer operative time in the SILC approach.

PMID- 22664894
TI  - A new approach to health services research.

PMID- 22664895
TI  - [Oscar Vulpius and tendon transfer in the hand].
AB  - Oscar Vulpius dealt extensively with the problem of tendon transfer for motoric
      deficits. An analysis of his works shows that the knowledge of tendon healing,
      aftercare and operative techniques was already very widely advanced at the
      beginning of the last century.

PMID- 22664896
TI  - Superior canal dehiscence size:  multivariate assessment of clinical impact.
AB  - OBJECTIVE: To examine the association between dehiscence length in patients with
      superior semicircular canal dehiscence syndrome and their clinical findings,
      including objective audiometric and vestibular testing results. STUDY DESIGN:
      Retrospective study. SETTING: Tertiary referral center. PATIENTS: Patients
      included in this study were diagnosed with superior semicircular canal dehiscence
      syndrome and underwent surgical repair of the dehiscence through middle fossa
      craniotomy. The dehiscence length was measured intraoperatively in all cases.
      MAIN OUTCOME MEASURES: Correlation between dehiscence length with pure-tone
      average (PTA), average bone-conduction threshold, maximal air-bone gap, cervical
      vestibular evoked myogenic potential thresholds, and presenting signs and
      symptoms. RESULTS: The correlation between dehiscence length and maximal air-bone
      gap was statistically significant on both univariate and multivariate regression
      analyses. The correlations between dehiscence length and PTA, average bone
      conduction threshold, cervical vestibular evoked myogenic potential threshold,
      and presenting signs and symptoms were not statistically significant. CONCLUSION:
      The dehiscence length correlated positively with the maximal air-bone gap in
      patients with superior semicircular canal dehiscence. The correlation was
      statistically significant. The dehiscence length did not correlate with the other
      variables examined in this study.

PMID- 22664897
TI  - Clinical factors associated with prolonged recovery after superior canal
      dehiscence surgery.
AB  - OBJECTIVE: To identify clinical factors associated with prolonged recovery after
      superior canal dehiscence surgery. STUDY DESIGN: Retrospective review. SETTING:
      Tertiary care academic medical center. PATIENTS: Thirty-three patients that
      underwent surgery for SCDS were identified from a database of 140 patients
      diagnosed with SCD (2000-2010) at the Massachusetts Eye and Ear Infirmary
      (U.S.A.). The diagnosis of SCDS was based on clinical signs and symptoms,
      audiometric and vestibular testing and high-resolution temporal bone computed
      tomography. INTERVENTION: For the primary repair, the superior canal was plugged
      in 31 patients through a middle fossa craniotomy approach and in 1 patient
      through a transmastoid approach. In 1 patient, the SCD was resurfaced through a
      middle fossa craniotomy approach. MAIN OUTCOME MEASURES: Postoperative clinical
      signs and symptoms and factors that may influence duration of disequilibrium
      after surgery. RESULTS: Thirty-three patients (15-71 yr; mean, 43 yr) underwent
      surgery for SCDS on 35 ears (2 bilateral). Mean follow-up was 28.7 months (range,
      3 mo to 10 yr); 33 of 33 (100%) patients experienced initial improvement of the
      chief complaint. Three patients required revision surgery, improving symptoms in
      2 patients. Six patients had dizziness lasting more than 4 months
      postoperatively, and all had bilateral SCD, migraines, and a dehiscence of 3 mm
      or greater. CONCLUSION: Surgical plugging of SCD is an effective management
      option to provide long-term improvement of the chief complaint in SCDS patients.
      Patients with bilateral SCD, a history of migraines, and larger defects may be at
      risk of prolonged recovery and should be appropriately counseled.

PMID- 22664898
TI  - A novel method to determine standardized anatomic dimensions of the osseous
      external auditory canal.
AB  - OBJECTIVE: To introduce a novel method for measuring the dimensions of the
      osseous external auditory canal (OEAC) on computed tomographic images of the
      temporal bone. STUDY DESIGN: Radiology case series. SETTING: Tertiary care
      medical center. PATIENTS: A retrospective review of high-resolution computed
      tomographic images of the temporal bones of 69 patients (120 ears) between the
      ages of 5 and 85 years (mean, 29.1 yr) was performed. MAIN OUTCOME MEASURES:
      Using a novel method to measure dimensions of the OEAC in the parasagittal
      planes, 6 defined dimensions as well as length and shape of the OEAC were studied
      at the annulus, midcanal, and the border of the bony cartilaginous junction.
      RESULTS: There was no statistically significant difference in OEAC dimensions
      between the male and female subjects or patients with and without a history of
      chronic otitis media within similar age groups. The length of the OEAC was
      significantly different between age groups of 5 to 12 and older than 13 years.
      The 6 defined dimensions were statistically different between the age groups of 5
      to 8 years and older. These dimensions were not statistically different between
      the age groups of 9 to 12, 13 to 18, and older than 18 years. The most prevalent
      shape of the OEAC was conical (64%). CONCLUSION: Standardized anatomic dimensions
      of the OEAC provide important measurements for design of novel in-the-canal
      hearing aids and specialized earplugs and assist in defining average sizes for
      canalplasty procedures.

PMID- 22664899
TI  - Preoperative assessment of taste function in patients with middle ear disease.
AB  - OBJECTIVE: To identify differences in taste function among patients with chronic
      otitis media, cholesteatoma, and noninflammatory disease before middle ear
      surgery. STUDY DESIGN: Retrospective analysis. SETTING: Tertiary referral
      hospital. PATIENTS: Two hundred thirty ears underwent primary middle ear surgery
      from January 2006 to December 2010. The subjects consisted of 84 men and 146
      women with ages ranging from 20 to 60 years (mean, 43.9 yr). There were 95 ears
      with chronic otitis media, 61 ears with pars flaccida retraction-type
      cholesteatoma, 22 ears with pars tensa retraction-type cholesteatoma, and 52 ears
      with noninflammatory diseases such as otosclerosis and ossicular anomalies. MAIN
      OUTCOME MEASURE: The patients underwent taste testing using electrogustometry and
      the filter paper disk method in the regions controlled by the chorda tympani
      nerve. RESULTS: None of the patients complained of taste dysfunction before
      middle ear surgery. Among the 4 groups, the patients with pars tensa retraction
      type cholesteatoma displayed the highest electrogustometry threshold. The filter
      paper disk method did not detect any significant differences among the 4 groups.
      CONCLUSION: Our findings suggest that the filter paper disk scores of all taste
      qualities (sweet, salty, sour, and bitter tastes) are not deteriorated
      preoperatively during chronic inflammation in the middle ear and that taste
      function is affected most in patients with pars tensa retraction-type
      cholesteatoma.

PMID- 22664900
TI  - Cochlear implantation in patients with neurofibromatosis type 2:  variables
      affecting auditory performance.
AB  - OBJECTIVE: To investigate cochlear implant performance outcomes among patients
      with Neurofibromatosis type 2 (NF2). STUDY DESIGN: Retrospective case series,
      patient questionnaire, and systematic review of the literature. SETTING: Tertiary
      academic referral center. PATIENTS: All patients with NF2 having an anatomically
      intact ipsilateral cochlear nerve who underwent cochlear implantation (CI).
      INTERVENTION(S): Cochlear implantation. MAIN OUTCOME MEASURES: Postimplantation
      audiometric performance and patient perceived benefit. RESULTS: Ten patients met
      study criteria. The median duration of follow-up after CI was 42 months (mean,
      46.9 mo; range, 12-97 mo). Five patients received previous microsurgical
      resection of their ipsilateral vestibular schwannoma, 4 underwent previous
      stereotactic radiosurgery, and 1 patient had no tumor treatment before CI. Nine
      subjects achieved sound awareness, 6 attained open-set speech recognition and 7
      are daily users. Variables including prolonged auditory deprivation, cochlear
      ossification, unfavorable electrical promontory stimulation testing, and useful
      contralateral hearing were associated with poor cochlear implant performance. No
      statistical associations were found between open-set recognition capacity and
      previous tumor management strategy, surgical approach, or ipsilateral tumor size.
      CONCLUSION: Cochlear implantation is an attractive alternative to auditory
      brainstem implantation for hearing rehabilitation in patients with NF2.
      Approximately 70% of patients achieve open-set speech discrimination, many
      scoring at the ceiling of audiometric testing. Given a favorable risk profile and
      superior audiometric outcomes, CI should be strongly considered in patients with
      nonserviceable hearing who have an anatomically intact cochlear nerve, whereas
      auditory brainstem implantation should be reserved for patients with evidence of
      cochlear nerve loss. Akin to conventional cochlear implant recipients, prolonged
      hearing loss, unfavorable electrophysiological testing, and cochlear ossification
      may predict poor subject performance. Finally, useful hearing in the
      contralateral ear may present a barrier to daily device use.

PMID- 22664901
TI  - Prospective evaluation of the clinical profile and referral pattern differences
      of vestibular schwannomas and other cerebellopontine angle tumors.
AB  - OBJECTIVE: To evaluate the clinical profile, referral pattern, delay in
      diagnosis, and impact of tumor size of cases involving vestibular schwannomas
      (VS) versus other cerebellopontine angle (CPA) tumors in an Egyptian population.
      STUDY DESIGN: Case series study. SETTING: Tertiary referral center. PATIENTS: A
      prospective study of possible retrocochlear lesions was conducted from 2008 to
      2010. INTERVENTION(S): Patients were subjected to a full clinical history,
      complete otorhinolaryngological examination, a basic audiologic evaluation,
      auditory brainstem response assay, and gadolinium-enhanced magnetic resonance
      imaging. According to the findings of magnetic resonance imaging, patients with
      retrocochlear lesions were divided into 2 groups: those with VS (n = 17) and
      those with other CPA lesions (n = 14). MAIN OUTCOME MEASURE(S): Diagnostic delay
      and criteria of VS and CPA tumors. RESULTS: Unilateral hearing loss and tinnitus
      were presented in 52.9% of VS cases with a diagnostic delay of 15.5 months. For
      cases involving other CPA lesions, a combination of otologic symptoms was
      observed in 9 (64%) of 14 cases, and a diagnostic delay of 47.5 months was
      experienced. An absence of auditory brainstem response waves was identified
      significantly (p < 0.05) for the affected ears of both groups. Only differences
      in Wave V latency were significant between the 2 groups (p < 0.05). CONCLUSION: A
      longer diagnostic delay was associated with cases involving other types of CPA
      lesions versus cases of VS, and tumor size and volume did not affect the
      diagnostic delay of the former. Moreover, the only significant difference in
      clinical presentation for these 2 groups of intracranial tumor involved Wave V
      latency.

PMID- 22664902
TI  - Bone-anchored hearing device surgery:  a 3- to 6-year follow-up with life table
      and worst-case scenario calculation.
AB  - BACKGROUND: Published studies on complications for the bone-anchored hearing
      devices can present different outcomes. Unfortunately, data are often difficult
      to interpret, compare, or use in meta-analysis owing to missing data. This study
      presents a sensitivity analysis of presenting cohort data, which considers
      incomplete follow-up data. An example is given using life table calculations and
      worst-case scenarios for implant losses and revision surgeries after installing
      BAHA. METHODS: A retrospective case review of all patients consecutively operated
      on for BAHA between 2005 and 2007 with a 1-stage procedure. Life table
      calculations were used to handle incomplete follow-up data, including 50% of
      patients lost to follow-up as failures. In addition, a worst-case scenario was
      calculated, in which 100% of patients lost to follow-up were considered to be
      failures. RESULTS: A total of 138 patients were operated on at Sahlgrenska, with
      a follow-up time of 3 to 5 years. Within the study cohort, 9 patients (6.5%) lost
      the implant. Reasons for incomplete follow-up data were as follows: "lost to
      follow-up" (n = 4), "not using BAHA" (n = 3), and "patient was deceased" (n = 2).
      Life table calculation gave a calculated implant loss of 9.8%. The worst-case
      scenario gave an implant loss frequency of 13%. Revision surgery was performed in
      3 (2.2%) of 138 patients in the study cohort. With life table and worst-case
      scenario calculations, the frequency of revision surgery was 6.2% and 10.1%,
      respectively. CONCLUSION: Incomplete follow-up data can theoretically affect
      outcome data considerably. Therefore, outcome data should also be presented with
      life table and worst-case scenario. This would enhance the possibility to
      interpret and compare data.

PMID- 22664903
TI  - Fungal malignant otitis externa:  pitfalls, diagnosis, and treatment.
AB  - HYPOTHESIS: Oral voriconazole is a viable alternative modality treatment to
      traditionally used intravenous vancomycin in the treatment of malignant otitis
      externa (MOE). BACKGROUND: The incidence of MOE is on the rise, more so in Saudi
      Arabia where diabetes mellitus is endemic. Although Pseudomonas aeruginosa is the
      most common offending organism, we are observing an increasing number of fungal
      MOE, in particular, Aspergillus species. The clinical findings in these patients
      can be quite different from those of the classic gram-negative bacteria. METHODS:
      Chart review of patients with a diagnosis of MOE who underwent oral voriconazole
      treatment. RESULTS: Three cases of Aspergillus MOE are reported in detail,
      pointing the pitfalls in clinical findings, diagnosis, and management of this
      entity. CONCLUSION: Oral voriconazole proved to be an excellent alternative
      modality treatment in this population of patients with MOE.

PMID- 22664904
TI  - Scalar localization by computed tomography of cochlear implant electrode carriers
      designed for deep insertion.
AB  - OBJECTIVES: This study aimed to evaluate the possibility of predicting
      radiologically the scalar localization of a 31.5-mm-long, free-fitting electrode
      carrier for cochlear implantation, using conventional planar computed tomography.
      STUDY DESIGN: A cross-sectional human temporal bone study was conducted. SETTING:
      Twenty human temporal bones were acquired postmortem and implanted with 31.5-mm
      long electrode carriers. Ten of these were implanted into the scala tympani using
      the round window approach, whereas the other 10 electrodes were inserted into the
      scala vestibuli by cochleostomy. Computed tomography was then performed, and 2
      experienced blinded radiologists evaluated the intracochlear position of the
      array. MAIN OUTCOME MEASURE: The estimated position of the electrode carrier was
      described using a 5-point scale. After sectioning and histologic investigation,
      the results of the radiologic and histologic investigations were compared.
      RESULTS: In 17 of 20 cases, it was possible to estimate the correct position of
      the electrode carrier within the basal turn of the cochlea by means of computed
      tomography. As the insertion angles widened beyond 360 degrees, it became
      increasing difficult for the radiologists to correctly determine the position of
      the electrode carrier. CONCLUSION: The comparison of our temporal bone experiment
      results with the computed tomography results revealed the difficulty of assessing
      the correct position of intracochlear electrodes. Scalar localization of deeply
      inserted electrode carriers cannot be precisely determined by means of computed
      tomography.

PMID- 22664905
TI  - Congenital oval or round window anomaly with or without abnormal facial nerve
      course:  surgical results for 15 ears.
AB  - OBJECTIVES: To describe the audiometric results in a consecutive series of
      patients with congenital ossicular aplasia (Class 4a) or dysplasia of the oval
      and/or round window (Class 4b), which might include a possible anomalous course
      of the facial nerve. STUDY DESIGN: Retrospective chart study. SETTING: Tertiary
      referral center. PATIENTS: A tertiary referral center study with a total of 14
      patients with congenital minor ear anomalies as part of a consecutive series (n =
      89) who underwent exploratory tympanotomies (15 ears). MAIN OUTCOME MEASURES:
      Audiometric results. RESULTS: In 8 of 15 ears, ossicular reconstruction was
      attempted. In the short term (1 mo), there was a serviceable hearing outcome (air
      bone gap closure to within 25 dB) in 4 ears. However, the long-term results
      showed deterioration because of an increased air-bone gap in all but 1 ear. No
      facial nerve lesion was observed postoperatively. CONCLUSION: Congenital
      dysplasia or aplasia of the oval and/or round window is an uncommon congenital
      minor ear anomaly. Classical microsurgical opportunities are rare in this group
      of anomalies. Newer options for hearing rehabilitation, such as the
      osseointegrated passive bone conduction devices, have become viable alternatives
      for conventional air conduction hearing devices. In the near future, upcoming
      active bone conduction devices might become the most preferred surgical option.
      In cases in which the facial nerve is only partially overlying the oval window, a
      type of malleostapedotomy procedure might result in a serviceable postoperative
      hearing level.

PMID- 22664907
TI  - CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation
      embryo development.
AB  - Although HCO(3)(-) is known to be required for early embryo development, its
      exact role remains elusive. Here we report that HCO(3)(-) acts as an
      environmental cue in regulating miR-125b expression through CFTR-mediated influx
      during preimplantation embryo development. The results show that the effect of
      HCO(3)(-) on preimplantation embryo development can be suppressed by interfering
      the function of a HCO(3)(-)-conducting channel, CFTR, by a specific inhibitor or
      gene knockout. Removal of extracellular HCO(3)(-) or inhibition of CFTR reduces
      miR-125b expression in 2 cell-stage mouse embryos. Knockdown of miR-125b mimics
      the effect of HCO(3)(-) removal and CFTR inhibition, while injection of miR-125b
      precursor reverses it. Downregulation of miR-125b upregulates p53 cascade in both
      human and mouse embryos. The activation of miR-125b is shown to be mediated by
      sAC/PKA-dependent nuclear shuttling of NF-kappaB. These results have revealed a
      critical role of CFTR in signal transduction linking the environmental HCO(3)(-)
      to activation of miR-125b during preimplantation embryo development and indicated
      the importance of ion channels in regulation of miRNAs.

PMID- 22664910
TI  - Nuclear Receptors in atherosclerosis: a superfamily with many 'Goodfellas'.
AB  - Nuclear Receptors form a superfamily of 48 transcription factors that exhibit a
      plethora of functions in steroid hormone signaling, regulation of metabolism,
      circadian rhythm and cellular differentiation. In this review, we describe our
      current knowledge on the role of Nuclear Receptors in atherosclerosis, which is a
      multifactorial disease of the vessel wall. Various cell types are involved in
      this chronic inflammatory pathology in which multiple cellular processes and
      numerous genes are dysregulated. Systemic risk factors for atherosclerosis are
      among others adverse blood lipid profiles, enhanced circulating cytokine levels,
      as well as increased blood pressure. Since many Nuclear Receptors modulate lipid
      profiles or regulate blood pressure they indirectly affect atherosclerosis. In
      the present review, we focus on the functional involvement of Nuclear Receptors
      within the atherosclerotic vessel wall, more specifically on their modulation of
      cellular functions in endothelial cells, smooth muscle cells and macrophages.
      Collectively, this overview shows that most of the Nuclear Receptors are athero
      protective in atherosclerotic lesions.

PMID- 22664909
TI  - 5-Aza-2'-deoxycytidine induces cytotoxicity in BGC-823 cells via DNA
      methyltransferase 1 and 3a independent of p53 status.
AB  - The DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR) has therapeutic
      value for the treatment of cancer. However, the mechanism by which 5-Aza-CdR
      induces antineoplastic activity is not clear. The efficacy of 5-Aza-CdR on the
      contribution of gene reactivation by demethylation and enzyme-DNA adduct
      formation is an important unresolved question. The aim of this study was to
      explore the mechanism of the effect of 5-Aza-CdR on human gastric cancer growth.
      Human BGC-823 cells were treated with different concentrations of 5-Aza-CdR for
      different durations. Cell viability, DNA damage and gene expression were
      determined. The results showed that 5-Aza-CdR at low concentrations induced
      inhibition of gastric cancer BGC-823 cell proliferation as well as increased
      apoptosis caused by DNA damage. For the first time, we demonstrated that 5-Aza
      CdR-induced cytotoxicity against BGC-823 cells was predominantly regulated via
      upregulation of DNA methyltransferase 1, 3a and partially via reactivation of
      RUNX3, which was independent of p53 status and its ability to activate
      p21Waf1/Cip1 expression. To our knowledge, this is the first demonstration of p53
      independent 5-Aza-CdR action on DNA methyltransferases and demethylation. These
      results strongly provide the preclinical rationale for the clinical evaluation of
      5-Aza-CdR to improve patient outcome in gastric cancer.

PMID- 22664911
TI  - Bronchogenic cysts in retroperitoneal region.
AB  - Bronchogenic cyst is a relatively rare abnormality that develop from the
      accessory lung buds of the foregut. The cyst is regarded as a congenital
      developmental abnormality. Occurence in the retroperitoneal presentation is rare.
      Here, we present two patients who had an incidentally discovered retroperitoneal
      mass which were revealed to be bronchogenic cysts after surgical extirpation.

PMID- 22664913
TI  - Non-coding RNA and disease.

PMID- 22664908
TI  - G protein-coupled receptors as therapeutic targets for multiple sclerosis.
AB  - G protein-coupled receptors (GPCRs) mediate most of our physiological responses
      to hormones, neurotransmitters and environmental stimulants. They are considered
      as the most successful therapeutic targets for a broad spectrum of diseases.
      Multiple sclerosis (MS) is an inflammatory disease that is characterized by
      immune-mediated demyelination and degeneration of the central nervous system
      (CNS). It is the leading cause of non-traumatic disability in young adults. Great
      progress has been made over the past few decades in understanding the
      pathogenesis of MS. Numerous data from animal and clinical studies indicate that
      many GPCRs are critically involved in various aspects of MS pathogenesis,
      including antigen presentation, cytokine production, T-cell differentiation, T
      cell proliferation, T-cell invasion, etc. In this review, we summarize the recent
      findings regarding the expression or functional changes of GPCRs in MS patients
      or animal models, and the influences of GPCRs on disease severity upon genetic or
      pharmacological manipulations. Hopefully some of these findings will lead to the
      development of novel therapies for MS in the near future.

PMID- 22664912
TI  - Are there gender-specific aspects of sleeve gastrectomy-data analysis from the
      quality assurance study of surgical treatment of obesity in Germany.
AB  - Since 1 January 2005, the situation of bariatric surgery has been examined in
      Germany. All data are registered prospectively in cooperation with the Institute
      of Quality Assurance in Surgery at the Otto-von-Guericke University Magdeburg.
      Data are registered in an internet online database. Data collection on the
      results of sleeve gastrectomy was started in 2006. Follow-up data were collected
      once a year. Participation in the quality assurance study is voluntary. Since
      2005, 3,125 sleeve gastrectomies have been performed in 80 hospitals. The number
      of procedures has increased from 1 in 2005 to 1,564 in 2010. Initially, the
      leakage rate was 7 % in 2007. The leakage rate dropped to 1.7 in 2010. The mean
      age of patients was 43.5 years and mean body mass index (BMI) was 52.03 kg/m(2).
      BMI and comorbidities are significantly higher in male than in female patients.
      The leakage rate in female patients was, at 1.60 %, significantly lower than in
      male patients, at 3.28 %. Sleeve gastrectomy is becoming more and more popular in
      Germany. But the postoperative complication rate is still high. Data from the
      nationwide survey of bariatric surgery in Germany show significant differences in
      preoperative comorbidities and complication rates between male and female
      patients. There is a need for further evaluation of gender-specific aspects to
      optimize patient selection and reduce specific postoperative complications.

PMID- 22664914
TI  - MicroRNA-mediated regulation of gene expression is affected by disease-associated
      SNPs within the 3'-UTR via altered RNA structure.
AB  - Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) or their target
      sites (miR-SNPs) within the 3'-UTR of mRNAs are increasingly thought to play a
      major role in pathological dysregulation of gene expression. Here, we studied the
      functional role of miR-SNPs on miRNA-mediated post-transcriptional regulation of
      gene expression. First, analyses were performed on a SNP located in the miR-155
      target site within the 3'-UTR of the Angiotensin II type 1 receptor (AGTR1;
      rs5186, A > C) mRNA. Second, a SNP in the 3'-UTR of the muscle RAS oncogene
      homolog (MRAS; rs9818870, C > T) mRNA was studied which is located outside of
      binding sites of miR-195 and miR-135. Using these SNPs we investigated their
      effects on local RNA structure, on local structural accessibility and on
      functional miRNA binding, respectively. Systematic computational RNA folding
      analyses of the allelic mRNAs in either case predicted significant changes of
      local RNA structure in the vicinity of the cognate miRNA binding sites.
      Consistently, experimental in vitro probing of RNA showing differential cleavage
      patterns and reporter gene-based assays indicated functional differences of miRNA
      mediated regulation of the two AGTR1 and MRAS alleles. In conclusion, we describe
      a novel model explaining the functional influence of 3'-UTR-located SNPs on miRNA
      mediated control of gene expression via SNP-related changes of local RNA
      structure in non-coding regions of mRNA. This concept substantially extends the
      meaning of disease-related SNPs identified in non protein-coding transcribed
      sequences within or close to miRNA binding sites.

PMID- 22664916
TI  - MicroRNAs in diabetes and diabetes-associated complications.
AB  - Diabetes mellitus due to its high prevalence and associated complications is a
      major socioeconomic health problem. Diabetes is characterized by multiple macro-
      and microvascular complications (e.g. diabetic nephropathy, cardiomyopathy,
      neuropathy, retinopathy). Research efforts aim to elucidate pathophysiological
      mechanisms contributing to the disease process. MicroRNAs are endogenous small
      single stranded molecules regulating targets through mRNA cleavage or
      translational inhibition. MicroRNAs regulate many biological cellular functions
      and are often deregulated during diseases. The aim of the present article is to
      summarize the current knowledge of the impact of microRNAs on the development of
      diabetes and its associated complications including endothelial and vascular
      smooth muscle cell dysfunction, diabetic cardiomyopathy, diabetic nephropathy,
      regulation of pancreatic beta cell function as well as skeletal muscle and
      hepatic involvement.

PMID- 22664915
TI  - The hallmarks of cancer: a long non-coding RNA point of view.
AB  - With the advent of next generation sequencing methods and progress in
      transcriptome analysis, it became obvious that the human genome contains much
      more than just protein-coding genes. In fact, up to 70% of our genome is
      transcribed into RNA that does not serve as templates for proteins. In this
      review, we focus on the emerging roles of these long non-coding RNAs (lncRNAs) in
      the field of tumor biology. Long ncRNAs were found to be deregulated in several
      human cancers and show tissue-specific expression. Functional studies revealed a
      broad spectrum of mechanisms applied by lncRNAs such as HOTAIR, MALAT1, ANRIL or
      lincRNA-p21 to fulfill their functions. Here, we link the cellular processes
      influenced by long ncRNAs to the hallmarks of cancer and therefore provide an
      ncRNA point-of-view on tumor biology. This should stimulate new research
      directions and therapeutic options considering long ncRNAs as novel prognostic
      markers and therapeutic targets.

PMID- 22664918
TI  - MicroRNA expression changes after lung cancer resection: a follow-up study.
AB  - MiRNAs are powerful biomarkers for detecting various diseases from tissue and
      body fluids. The potential of these molecules to monitor patients over time has,
      however, been less explored. We followed the fate of the plasma miRNome of lung
      cancer patients starting prior to surgery and ending 18 mo after surgery, with
      blood taken at three-month intervals. Principal component and clustering analysis
      showed that the differences of the overall miRNA patterns between the different
      time points were significantly smaller than between patients. For each patient we
      found a rather specific fluctuating miRNA pattern. We identified miRNAs that
      showed a significant correlation between expression level and time distance from
      surgery. A network analysis revealed 12 correlated miRNAs regulating 48 genes
      that were deregulated in lung cancer tissue. Our data underline the importance of
      studies that follow the fate of miRNAs over time, both to further our
      understanding of the biology of miRNA signatures and to establish these
      signatures as biomarkers.

PMID- 22664917
TI  - MicroRNAs, wild-type and mutant p53: more questions than answers.
AB  - The tumor suppressor p53 is a sequence-specific transcription factor that
      activates the expression of genes involved in apoptosis, cell cycle arrest and
      senescence. p53 can also inhibit gene expression and this effect is partly
      mediated by inducing several microRNAs (miRNAs). MiRNAs have emerged as a new
      class of regulators of the expression and function of eukaryotic genomes. Tumor
      suppressive or oncogenic functions have been attributed to some miRNAs. Recent
      studies have shown that p53 can alter the transcription of several miRNAs, and in
      some cases, it can also influence miRNA maturation. Conversely, miRNAs can also
      modulate the abundance and activity of p53 by direct or indirect mechanisms.
      Moreover, mutant p53 can actively repress the expression of some miRNAs that are
      activated by wild-type p53. In this review, we discuss recent evidences of this
      crosstalk between miRNAs and the p53 network and also highlight its implications
      in cancer.

PMID- 22664920
TI  - The mammalian microRNA response to bacterial infections.
AB  - MicroRNAs are small RNAs that post-transcriptionally regulate eukaryotic gene
      expression. In addition to their involvement in a wide range of physiological and
      pathological processes, including viral infections, microRNAs are increasingly
      implicated in the eukaryotic response to bacterial pathogens. Recent studies have
      characterized changes in host microRNA expression following infection with
      exclusively extracellular (Helicobacter pylori) or intracellular (Salmonella
      enterica) Gram-negative bacteria, as well as in the response to Gram-positive
      (Listeria monocytogenes) and other pathogens (Mycobacterium and Francisella
      species). In this review, we discuss the emerging roles of microRNAs in mammalian
      host signaling and defense against bacterial pathogens.

PMID- 22664921
TI  - MiRNAs and neural stem cells: a team to treat Parkinson's disease?
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder with no proven
      neuroprotective or neurorestorative therapies. During disease progression,
      degeneration of dopaminergic neurons of the central nervous system occurs.
      Therefore, therapies that either aim on the inhibition of this degeneration or on
      the replacement of the degenerated neurons are needed. On the one hand, arrest of
      degeneration might be achievable through specific inhibition of disease
      associated genes like alpha-Synuclein or Leucine rich repeat kinase 2 (LRRK2). On
      the other hand, based on neural stem cells that bear the ability to generate new
      dopaminergic neurons, replacement of degenerated cells could be accomplished.
      Since both approaches can be regulated by micro-RNAs, these molecules have an
      enormous therapeutic potential. In this review, we will focus on the
      neurobiological and neurodegenerative implications of miRNAs and highlight their
      role in stem cell fate decisions. Finally, we will discuss their potential as
      therapeutic agents and targets for Parkinson's disease.

PMID- 22664919
TI  - Post-transcriptional regulation in metabolic diseases.
AB  - Post-transcriptional gene regulation by microRNAs (miRNAs) and RNA-binding
      proteins (RBPs) is central to many biological functions. Aberrant gene expression
      patterns underlie many metabolic diseases that represent major public health
      concerns and formidable therapeutic challenges. Several studies have established
      a number of post-transcriptional regulators implicated in metabolic diseases such
      as diabetes and obesity. In addition, emerging knowledge of metabolically active
      and insulin-sensitive organs, such as the pancreas, liver, muscle and adipose
      compartment, is rapidly expanding the panel of potential therapeutic targets for
      the treatment of metabolic diseases. Here, we review our current understanding of
      miRNAs and RBPs that affect glucose and lipid homeostasis, and their roles in
      normal physiology and metabolic disorders, especially type 2 diabetes and
      obesity.

PMID- 22664922
TI  - Regulation of BACE1 by miR-29a/b in a cellular model of Spinocerebellar Ataxia
      17.
AB  - Polyglutamine diseases are a class of neurodegenerative disorders characterized
      by expansion of polyglutamine repeats, protein aggregation and neuronal cell
      death in specific regions of the brain. The expansion of a polyglutamine repeat
      in the TATA binding protein (TBP) causes a neurodegenerative disease,
      Spinocerebellar Ataxia 17 (SCA17). This disease is characterized by intranuclear
      protein aggregates and selective loss of cerebellar neurons, including Purkinje
      cells. MicroRNAs are small, endogenous, regulatory non-coding RNA molecules that
      bind to messenger RNAs with partial complementarity and interfere in their
      expression. Here, we used a cellular model of SCA17 where we expressed TBP with
      16 (normal) or 59 (pathogenic) polyglutamines and found differential expression
      of several microRNAs. Specifically, we found two microRNAs, miR-29a/b, were down
      regulated. With miR-29a/b down regulation, we found an increased expression of
      targets of miR-29a/b -beta-site amyloid precursor protein cleaving enzyme 1
      (BACE1), p53 upregulated modulator of apoptosis (PUMA) and BAK, increased
      cytochrome c release and apoptosis. Restoration of miR-29a/b in the pathogenic
      polyglutamine background reduced the BACE1expression. While, antagomiRs against
      miR-29a/b resulted in an increase in BACE1 levels and neuronal apoptosis. In
      spite of the elevation of BACE1 in Alzhemiers disease, its role in neuronal cell
      death has not been established. Here, we show that increased BACE1 expression is
      not sufficient to cause apoptosis. However restoring level of BACE1 to normal in
      polyglutamine cells partially reduced neuronal apoptosis. We show a role for the
      miR-29a/b-BACE1 regulatory interaction in SCA17, suggesting that this microRNA
      could be part of a common molecular mechanism leading to neuronal cell death in
      multiple neurodegenerative disorders. The identification of a common mechanism of
      microRNA mediated neurodegeneration not only improves our understanding of the
      process, but also provides promising and novel therapeutic targets.

PMID- 22664923
TI  - Polymerase chain reaction: basic protocol plus troubleshooting and optimization
      strategies.
AB  - In the biological sciences there have been technological advances that catapult
      the discipline into golden ages of discovery. For example, the field of
      microbiology was transformed with the advent of Anton van Leeuwenhoek's
      microscope, which allowed scientists to visualize prokaryotes for the first time.
      The development of the polymerase chain reaction (PCR) is one of those
      innovations that changed the course of molecular science with its impact spanning
      countless subdisciplines in biology. The theoretical process was outlined by
      Keppe and coworkers in 1971; however, it was another 14 years until the complete
      PCR procedure was described and experimentally applied by Kary Mullis while at
      Cetus Corporation in 1985. Automation and refinement of this technique progressed
      with the introduction of a thermal stable DNA polymerase from the bacterium
      Thermus aquaticus, consequently the name Taq DNA polymerase. PCR is a powerful
      amplification technique that can generate an ample supply of a specific segment
      of DNA (i.e., an amplicon) from only a small amount of starting material (i.e.,
      DNA template or target sequence). While straightforward and generally trouble
      free, there are pitfalls that complicate the reaction producing spurious results.
      When PCR fails it can lead to many non-specific DNA products of varying sizes
      that appear as a ladder or smear of bands on agarose gels. Sometimes no products
      form at all. Another potential problem occurs when mutations are unintentionally
      introduced in the amplicons, resulting in a heterogeneous population of PCR
      products. PCR failures can become frustrating unless patience and careful
      troubleshooting are employed to sort out and solve the problem(s). This protocol
      outlines the basic principles of PCR, provides a methodology that will result in
      amplification of most target sequences, and presents strategies for optimizing a
      reaction. By following this PCR guide, students should be able to: * Set up
      reactions and thermal cycling conditions for a conventional PCR experiment *
      Understand the function of various reaction components and their overall effect
      on a PCR experiment * Design and optimize a PCR experiment for any DNA template *
      Troubleshoot failed PCR experiments.

PMID- 22664924
TI  - Sucking improvement following blood transfusion for anemia of prematurity.
AB  - OBJECTIVE: To determine whether correction of anemia of prematurity by packed red
      blood cell transfusion improves sucking. DESIGN: Nonexperimental intervention
      study. SETTING: Neonatal intensive care unit of Shaare Zedek Medical Center,
      Jerusalem, Israel, between July 23, 2006, and December 16, 2007. PATIENTS: Thirty
      six neonates at a gestational age of 34 weeks or younger, feeding orally, who
      developed anemia of prematurity. INTERVENTION: Packed red blood cell transfusion,
      15 mL/kg. MAIN OUTCOME MEASURES: Change in sucking parameters recorded with the
      Kron Nutritive Sucking Apparatus for 5 minutes and ingested volume, prior to and
      1 to 2 days after intervention. RESULTS: The mean (SD) gestational age was 30.1
      (2.1) weeks, and the mean (SD) birth weight was 1436 (45) g. At the time of the
      study, the mean (SD) postnatal age was 46 (26) days, the mean (SD) weight was
      2311 (36) g, and the mean (SD) hematocrit was 26.7% (2.6%). Overall, there was no
      change in the number of sucks, number of bursts, or maximum negative pressure
      generated. Daily weight gain increased after transfusion (mean [SD] weight gain,
      30.9 [10.0] g before transfusion vs 36.5 [13.0] g after transfusion; P=.02). The
      babies were then stratified into those below the median number of sucks (109
      sucks) before transfusion (poor feeders) and those at or above the median (better
      feeders). In the former subgroup only, changes from before transfusion to after
      transfusion were found in the number of sucks (mean [SD] sucks, 73.4 [29.5] vs
      108.9 [53.3], respectively; P=.006; mean [SD] sucks per burst, 3.4 [1.4] vs 4.9
      [2.8], respectively; P=.01) and volume consumed (mean [SD] volume, 17.1 [9.8] mL
      vs 23.2 [12.8] mL, respectively; P=.004). CONCLUSIONS: Correction of anemia of
      prematurity with blood transfusion improved sucking and volume ingested in
      premature infants who were poor feeders prior to the transfusion. It also
      enhanced overall weight gain.

PMID- 22664925
TI  - The microbiology of endophthalmitis: global trends and a local perspective.
AB  - Endophthalmitis is a rare but frequently devastating infection, caused by diverse
      organisms, including bacteria, viruses, fungi, and parasites. The causative
      agents of endophthalmitis vary according to the mechanism. The involvement of
      intraocular structures can result from exogenous spread from ocular trauma,
      infection of adjacent structures, or as a complication of intraocular surgery. Of
      the causes of exogenous endophthalmitis, post-operative endophthalmitis is the
      most frequently encountered; specifically, cataract surgery is the most frequent
      eye surgery and, thus, leads the list of surgery-associated endophthalmitis.
      Exogenous source is far more common than endogenous endophthalmitis, a disease
      that is caused by the hematogenous spread of organisms from a remote infectious
      site to the eye, leading to severe visual loss. Several large series estimate
      that endogenous endophthalmitis accounts for 2-15 % of all cases of
      endophthalmitis. Progressive vitritis is a hallmark for all forms of
      endophthalmitis, accompanied by intraocular inflammation, loss of vision, pain,
      and hypopyon. The common presentation consists of reduced vision, conjunctival
      injection, pain, and eyelid swelling. We reviewed the microbiology of
      endophthalmitis during a 9-year period in Winnipeg, Canada. Gram-positive
      bacteria with coagulase-negative staphylococci are the most common causative
      organisms, reflecting the association with surgical procedures.

PMID- 22664926
TI  - PPP2R2C as a candidate gene of a temperament and character trait-based
      endophenotype of ADHD.
AB  - There are several lines of evidence that the 4p16 region is a candidate locus of
      both attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder. None
      of the harbored candidate genes of this region were hitherto shown to be
      associated with ADHD despite promising functionality. One of the most promising
      candidate genes in this region is protein phosphatase 2, regulatory subunit B,
      gamma (PPP2R2C), which, however, thus far has not been assessed for a potential
      association with ADHD. A total of 513 in- and outpatients affected with adult
      ADHD and 536 controls as well as 170 nuclear families with 249 children affected
      with ADHD were genotyped for 35 SNPs, which tagged the promoter region, the 5'
      and 3' UTRs, and the exons of the PPP2R2C. Two independent samples provided
      evidence that the major G allele of rs16838844 increases risk toward ADHD.
      Allelic variations of PPP2R2C rs16838698 on the other hand might be associated
      with a variety of personality traits. There is evidence that allelic variation in
      PPP2R2C may be associated with a variety of personality traits and ADHD per se.
      Nevertheless, as all those conditions are comorbid, PPP2R2C might reflect a
      common underlying neurobiological risk factor.

PMID- 22664927
TI  - Prostate cancer: Ex vivo efficacy of heat shock protein 90 inhibitors.

PMID- 22664931
TI  - Prostate cancer: New PSA screening guideline faces widespread opposition.

PMID- 22664930
TI  - Iatrogenic obstruction after sling surgery.
AB  - Sling surgery has supplanted other anti-incontinence procedures as the treatment
      of choice for stress urinary incontinence. Iatrogenic obstruction after sling
      surgery is increasingly reported as the procedure becomes more and more popular.
      The rate of retention (defined as catheter-dependency for at least 28 days) has
      been estimated at 1-10%. Iatrogenic obstruction after sling surgery has a
      variable presentation and can include urinary urgency, urgency incontinence,
      hesitancy, straining to void, weak urinary stream, nocturia, incomplete emptying,
      frequency, dysuria or urinary tract infections. The evaluation and diagnosis rely
      upon a thorough patient history, physical examination, a urine flow test and
      postvoid residual volume. Cystoscopy and pressure-flow studies can also be
      considered. The single most important factor in the diagnosis of sling-related
      obstruction or voiding dysfunction is the temporal relationship between the sling
      procedure and onset of symptoms. Transient urinary retention can be managed with
      indwelling or intermittent catheter drainage. For those patients with moderate or
      symptomatic retention, surgical options for treatment include sling loosening,
      sling incision, sling excision, and urethrolysis. 

PMID- 22664934
TI  - Comparison of tear protein levels in breast cancer patients and healthy controls
      using a de novo proteomic approach.
AB  - Noninvasive biomarkers are urgently needed for early detection of breast cancer
      since the risk of recurrence, morbidity and mortality are closely related to
      disease stage at the time of primary surgery. In the past decade, many proteomics
      based approaches were developed that utilize the protein profiling of human body
      fluids or identification of putative biomarkers to obtain more knowledge on the
      effects of cancer emergence and progression. Herein, we report on an analysis of
      proteins in the tear fluid from breast carcinoma patients and healthy women using
      a de novo proteomic approach and 25 mixed samples from each group. This study
      included 25 patients with primary invasive breast carcinoma and 25 age-matched
      healthy controls. We performed a MALDI-TOF-TOF-driven semi-quantitative
      comparison of tear protein levels in cancer (CA) and control (CTRL) using a de
      novo approach in pooled samples. Over 150 proteins in the tear fluid of CTRL and
      CA were identified. Using an in-house-developed algorithm we found more than 20
      proteins distinctly upregulated or downregulated in the CTRL and CA groups. We
      identified several proteins that had modified expression in breast cancer
      patients. These proteins are involved in host immune system pathways (e.g., C1Q1
      or S100A8) and different metabolic cascades (ALDH3A or TPI). Further validation
      of the results in an independent population combined with individual protein
      profiling of participants is needed to confirm the specificity of our findings
      and may lead to a better understanding of the pathological mechanism of breast
      cancer.

PMID- 22664935
TI  - Impact of metabolic syndrome on various aspects of microcirculation and major
      adverse cardiac events in patients with ST-segment elevation myocardial
      infarction.
AB  - BACKGROUND: Microvascular impairment is associated with a poor prognosis even
      after successful percutaneous coronary intervention (PCI) in acute myocardial
      infarction. The aim of the present study was to examine the impact of metabolic
      syndrome (MetS) on various aspects of microvascular function and clinical
      outcomes. METHODS AND RESULTS: In 216 consecutive patients with ST-segment
      elevation myocardial infarction (STEMI) after successful primary PCI, data were
      collected and analyzed on epicardial coronary flow, ST-segment resolution (STR)
      on electrocardiography, maximum serum creatine kinase levels, and the incidence
      of major adverse cardiac events (MACE). The prevalence of MetS was 40.7% (88
      patients). Corrected Thrombolysis In Myocardial Infarction frame count was
      significantly higher in the MetS group than in the non-MetS group (28.1+/-9.4 vs.
      24.7+/-7.9, P=0.04). STR >=50% was observed in 51.1% and 69.5%, respectively
      (P=0.01). Patients with MetS also had higher maximum creatine kinase levels
      (3,470+/-2,320IU/L vs. 2,664+/-1,850IU/L, P=0.01). On logistic regression
      analysis after adjustment for confounders, MetS was an independent negative
      predictor of complete STR (odds ratio, 0.49; 95% confidence interval [CI]: 0.25
      0.95, P=0.03). On Cox multivariate analysis, MetS was an independent predictor
      for MACE (hazard ratio, 4.85; 95% CI: 1.28-18.3, P=0.02). CONCLUSIONS: MetS may
      damage microcirculation after direct PCI in patients with STEMI and lead to poor
      prognosis.

PMID- 22664936
TI  - Novel risk scoring system with preoperative objective parameters gives a good
      prediction of 1-year mortality in patients with a left ventricular assist device.
AB  - BACKGROUND: As we have previously reported, the preoperative profile defined by
      INTERMACS is a good predictor for the prognosis after left ventricular assist
      device (LVAD) implantation, but is largely dependent on the physician's decision.
      Several other risk stratification systems including objective parameters (eg,
      Leitz-Miller, Columbia, Seattle Heart Failure Model, APACHE II) have been
      proposed to estimate patient's mortality after LVAD implantation. METHODS AND
      RESULTS: According to the preoperative data from 59 patients who received LVAD
      (10 implantable, 49 extracorporeal) since 2002 through 2010, we performed a
      logistic analysis and constructed a new scoring system (ie, the TODAI VAD score
      (TVAD score), assigning 8 points to serum albumin <3.2mg/dl (odds ratio [OR]
      8.475), 7 points to serum total bilirubin >4.8mg/dl (OR 7.300), 6 points to left
      ventricular end-diastolic diameter <55mm (OR 5.917), 5 points to central venous
      pressure >11mmHg (OR 5.128)). The receiver-operating characteristic analysis
      showed that the area under the curve of our new scoring system (0.864) was
      significantly larger than any of the abovementioned 5 scoring methods (all
      P<0.05). With the TVAD score, low (0-8 points), intermediate (9-17 points), and
      high (18-26 points) risk strata had significantly different 1-year survival rates
      of 95%, 54%, and 14%, respectively (all P<0.001). CONCLUSIONS: The TVAD score can
      predict the prognosis after LVAD implantation much better than the previously
      known methods.

PMID- 22664937
TI  - The enhancement of tumor radioresponse by combined treatment with cepharanthine
      is accompanied by the inhibition of DNA damage repair and the induction of
      apoptosis in oral squamous cell carcinoma.
AB  - In the present study, we investigated whether treatment with cepharanthine, a
      biscoclaurine alkaloid extracted from Stephania cepharantha improves the response
      to radiotherapy in the oral squamous cell carcinoma (OSCC) cell lines, HSC2, HSC3
      and HSC4. We examined the potential mechanisms that may contribute to the
      enhanced radiation response induced by cepharanthine. Growth inhibition was
      observed in vitro with radiation or cepharanthine. A co-operative anti
      proliferative effect was obtained when cancer cells were treated with
      cepharanthine followed by radiation. Cepharanthine also promoted the mitotic
      death of 3 cell lines by radiation. The results from DNA damage repair analysis
      in the cultured OSCC cells demonstrated that cepharanthine had a strong
      inhibitory effect on DNA double-strand break (DSB) repair after radiation. The
      combined treatment of cepharanthine and radiation led to an increase in the sub
      G1 peak as shown by flow cytometry, and markedly induced apoptosis through the
      activation of caspase-3. Tumor xenograft studies demonstrated that the
      combination of cepharanthine and radiation caused growth inhibition and tumor
      regression of OSCC tumors in athymic mice; tumor volume was reduced from 765.7 to
      226.3 mm3 in HSC2 cells (p<0.01), 391.6 to 43.7 mm3 in HSC3 (p<0.01), and from
      572.6 to 174.2 mm3 in HSC4 cells (p<0.01). In addition, combined therapy markedly
      increased tumor cell apoptosis. Overall, we conclude that cepharanthine enhances
      tumor radioresponse by multiple mechanisms that may involve the induction of
      apoptosis and the inhibition of DNA DSB repair after exposure to radiation.

PMID- 22664938
TI  - The potential influence of 5-aminosalicylic acid on the induction of
      myelotoxicity during thiopurine therapy in inflammatory bowel disease patients.
AB  - OBJECTIVE: To investigate the potential influence of 5-aminosalicylic acid (5
      ASA) on the induction of myelotoxicity during thiopurine therapy in inflammatory
      bowel disease patients. METHODS: (a) The retrospective study included
      inflammatory bowel disease patients treated with azathioprine (AZA)/6
      mercaptopurine (6-MP). Thiopurine methyltransferase (TPMT) activity and 6
      thioguanine nucleotide (6-TGN) levels were detected at stable medication points.
      (b) The prospective study was performed in active disease patients: 4 weeks of
      AZA 50 mg/day followed by concomitant 5-ASA 3 g/day for another 4 weeks. 6-TGN
      was analyzed at weeks 4 and 8. RESULTS: (a) Of the 139 retrospective study
      patients, 45 were on AZA/6-MP+5-ASA and 94 on AZA/6-MP alone. The myelotoxicity
      rates were 47 and 16%, respectively. Multivariates regression analysis indicated
      that the administration of concomitant 5-ASA was the only risk factor associated
      with myelotoxicity (odds ratio=3.45, 95% confidence interval 1.31-9.04, P=0.01).
      (b) Thiopurine methyltransferase activity was not significantly different between
      patients on AZA/6-MP+5-ASA and patients on AZA/6-MP alone (P=0.78). (c) 6-TGN
      levels were significantly higher in samples on AZA/6-MP+5-ASA than those on AZA/6
      MP (P=0.003) alone. (d) Sixteen patients completed the prospective study. After 4
      weeks on AZA 50 mg/day, 6-TGN levels of 13 patients were less than 230 pmol/8*10
      RBC. After another 4 weeks' cotreatment with mesalazine 3 g/day, 12 patients had
      6-TGN levels at least 230 pmol/8*10 RBC, five patients had 6-TGN levels at least
      420 pmol/8*10 RBC, and two of these five patients developed myelotoxicity.
      CONCLUSION: The risk of thiopurine-induced myelotoxicity markedly increases in
      patients treated with combined 5-ASA and 2 mg/kg/day AZA therapy, which may be
      correlated to the increase in 6-TGN. 50 mg daily AZA when concomitant 5-ASA might
      help maintain an effective 6-TGN level without increasing the risk of
      myelotoxicity.

PMID- 22664939
TI  - Single nucleotide polymorphisms in C-type lectin genes, clustered in the IBD2 and
      IBD6 susceptibility loci, may play a role in the pathogenesis of inflammatory
      bowel diseases.
AB  - BACKGROUND AND AIM: The balance between microbes and host defence mechanisms at
      the mucosal frontier plays an important, yet unclarified role in the pathogenesis
      of inflammatory bowel disease (IBD). The importance of microorganisms in IBD is
      supported by the association of IBD with mutations in pattern recognition
      receptors (PRRs) such as NOD2 and TLR4. We aimed to examine whether polymorphisms
      in another type of PRRs, the so-called C-type lectin receptors (CLRs), are
      associated with IBD. Growing insights into the pathogenetic role of NOD2
      mutations in Crohn's disease (CD) and the fact that the majority of CLR-encoding
      genes are located in IBD susceptibility loci provide strong arguments for further
      exploration of the role of CLRs in IBD. METHODS: In this study, we selected four
      single nucleotide polymorphisms (SNPs) in different CLRs to determine whether
      there could be a role for these CLRs in IBD. Functional SNPs in the genes coding
      for the candidate CLRs DC-SIGN, LLT1, DCIR and MGL were examined. Genotyping of
      all SNPs was performed at the Academic Medical Center. In this study, around 1572
      samples were included from a maximum of 621 CD patients, 457 ulcerative colitis
      (UC) patients and 586 healthy controls (HCs). RESULTS AND CONCLUSION: No
      association was found between our IBD cohort and the candidate SNPs for DC-SIGN
      (CD/HC: P=0.25 and UC/HC: P=0.36), DCIR (CD/HC: P=0.22 and UC/HC: P=0.41) and MGL
      (CD/HC: P=0.37 and UC/HC: P=0.25). However, one polymorphism in LLT1 was found to
      be associated with our CD population (P<0.034). Our UC cohort was not associated
      with the variation in LLT1 (P=0.33). LLT1 is a ligand for the recently discovered
      CD161. CD161 is a new surface marker for human interleukin (IL)-17-producing Th17
      cells. The Th17 phenotype has been linked to CD by the fact that IL-22, IL-17 and
      IL-23 receptor levels are increased in CD. The signal transduction pathways
      involving LLT1 and CD161 are not completely clarified and are currently under
      investigation in our laboratory.

PMID- 22664940
TI  - Spontaneous clearance of hepatitis C infection after liver transplantation from
      IL28B rs12979860 CC donors.
AB  - Genetic polymorphisms adjacent to IL28B have been previously associated with
      spontaneous clearance of hepatitis C virus (HCV) and a higher rate of sustained
      virological response to interferon-based treatment in HCV genotype 1-infected
      patients. A recent study has shown that patients with the CC genotype of the
      rs12979860 single nucleotide polymorphism upstream from the IL28B gene are more
      likely to clear HCV spontaneously relative to the CT or TT genotype. In the liver
      transplant cohort, HCV recurs almost universally in patients with detectable HCV
      RNA at the time of transplantation. The spontaneous clearance of HCV infection
      after transplant is very rare. We report two cases of spontaneous clearance of
      HCV genotype 1 infection after liver transplantation from homozygous IL28B CC
      donors. This finding may be explained by alterations in the host immune responses
      to HCV after transplantation with a CC donor liver, which has potential
      implications for donor selection in HCV-positive recipients.

PMID- 22664941
TI  - Symptom-detected and screen-detected celiac disease and adult height:  a large
      cohort study.
AB  - OBJECTIVE: Nowadays, most patients with celiac disease are diagnosed in
      adulthood. However, undetected disease may already have been present in childhood
      and may have subsequently affected growth. Earlier data on the eventual adult
      height of patients with celiac disease have been scant and inconsistent. We aimed
      to assess the final height in a large cohort of symptom-detected and screen
      detected patients with celiac disease diagnosed in adulthood. PATIENTS AND
      METHODS: The height of 1084 patients with celiac disease diagnosed in adulthood
      was determined in five separate birth cohorts between the years 1920 and 1989.
      Further, the patients were evaluated in three different subgroups depending on
      whether they were diagnosed on the basis of gastrointestinal or extraintestinal
      symptoms or by serological screening. The population-based control group included
      112 340 patients in equal birth cohorts. RESULTS: In general, the mean adult
      height of patients with celiac disease was at the same level as in the population
      at large. In subgroup analysis, men with intestinal symptoms were shorter than
      the population controls in the birth cohort 1948-1961, and a similar trend was
      observed in the older cohorts. In women, the mean height was also reduced in the
      older birth cohorts, but predominantly among screen-detected patients. In the
      younger birth cohorts, height was reduced in neither sex compared with the
      population. CONCLUSION: In general, the mean adult height of patients with celiac
      disease is at the same level as that of the general population. In a subgroup
      analysis, reduced height was observed in some of the older, but not younger,
      birth cohorts.

PMID- 22664942
TI  - The epidemiology of drug recalls in the United States.

PMID- 22664943
TI  - [Ophthalmologists in the proximity of Adolf Hitler].
AB  - Adolf Hitler met or at least knew about 5 ophthalmologists. The chair of
      ophthalmology in Berlin, Walther Lohlein, personally examined Hitler's eyes at
      least two times. The chair of ophthalmology in Breslau, Walter Dieter, developed
      "air raid protection spectacles" with the aid of high representatives of the NS
      system and probably Adolf Hitler himself. Heinrich Wilhelm Kranz became rector of
      the universities of Giessen and Frankfurt/Main. He was known as a very strict
      advocate of the NS-race hygiene. Werner Zabel made plans for Hitler's diet and
      tried to interfere with Hitler's medical treatment. Finally, Hellmuth Unger was
      an influential representative of the medical press and a famous writer. Three of
      his novels with medical topics were made into a film which Hitler probably saw.
      Hitler had, so to say, a small "ophthalmological proximity" which, however, did
      not play a significant role for himself or the NS-state.

PMID- 22664944
TI  - Association of the CYP1A1*2A, GSTT1 null, GSTM1 null, mEPHX*3, and XRCC1-399
      genetic polymorphisms with ulcerative colitis.

PMID- 22664945
TI  - Neuroprotective effect of neurotropin on chronic oxaliplatin-induced
      neurotoxicity in stage II and stage III colorectal cancer patients: results from
      a prospective, randomised, single-centre, pilot clinical trial.
AB  - BACKGROUND: Oxaliplatin is effective in adjuvant and first-line colorectal cancer
      chemotherapy. Oxaliplatin-induced severe chronic neurotoxicity is the main dose
      limiting adverse event. No standard treatment for oxaliplatin-induced chronic
      neurotoxicity has been identified. MATERIALS AND METHODS: We conducted a
      prospective pilot clinical trial to explore whether neurotropin has
      neuroprotective effects on chronic neurotoxicity. From May 1, 2010 to May 1,
      2011, 80 stage II and III colorectal cancer patients who were eligible to receive
      oxaliplatin-based chemotherapy voluntarily enrolled in the trial. The patients
      were randomly divided into two groups, one of which received neurotropin
      treatment. RESULTS: The patients in the control group experienced significantly
      >= grade 2 and >= grade 3 neurotoxicity (by NCI CTCAE grading) than those in the
      neurotropin group (60.9 vs. 21.1 %, for at least grade 2 neurotoxicity, P =
      0.001; 39 vs. 2.7 %, for at least grade 3 neurotoxicity, P < 0.001). If
      neurotoxicity was assessed by oxaliplatin-specific neurotoxicity grading, the
      patients in the control group also experienced significantly more >= grade 2
      neurotoxicity (51.2 vs. 12.5 %, P = 0.001). Neurotropin was the only factor that
      affected the incidence of >= grade 2 neurotoxicity in the multivariate Cox
      proportional hazards regression analysis. CONCLUSION: Neurotropin combined with
      oxaliplatin decreases chronic neurotoxicity effectively and safely.

PMID- 22664946
TI  - Sutureless primary repair of colonic perforation with a degradable stent in a
      porcine model of fecal peritonitis.
AB  - PURPOSE: Colonic perforation with fecal peritonitis is a life-threatening
      clinical condition. For these patients, a two-stage operation of fecal diversion
      and a postponed colostomy closure is generally recommended. Accordingly, a simple
      and feasible primary repair technique was explored. METHODS: A sutureless banding
      method using a biodegradable stent and a porcine model of artificial colonic
      perforation were introduced. The colonic perforation model was created
      successfully with an open procedure in 34 pigs. The primary repair with a stent
      or the conventional hand-sewn control was performed 72 h later. Morbidity and
      mortality were recorded. Pigs in each group were also sacrificed to evaluate the
      healing on postoperative days (PODs) 3, 7, 14, and 90. The peripheral white blood
      cell counts, albumin, anastomotic bursting pressure, hydroxyproline contents, and
      histology data were evaluated. RESULTS: There were 17 pigs in either group. Four
      pigs (23.5 %) of the control group died, but no mortality occurred in the stent
      group. There were no significant differences in white blood cell counts and
      albumin. Though anastomotic hydroxyproline contents between the two groups were
      comparable, the collagen per protein ratio on POD 14 in the stent group was
      higher, as well as the bursting pressure on PODs 3 and 7. Microscopically, the
      local inflammation of the cut edges in the control group was more severe, and the
      collagen synthesis started later. CONCLUSIONS: A sutureless primary repair of a
      colonic perforation with a degradable stent is a feasible method in a porcine
      model of fecal peritonitis.

PMID- 22664947
TI  - Active infective endocarditis due to Erysipelothrix rhusiopathiae: zoonosis
      caused by vancomycin-resistant gram-positive rod.
AB  - A 42-year-old female who was a voluntary worker in a school for handicapped
      children was referred to us for surgery for active infective endocarditis. Trans
      esophageal echocardiography showed 2 large mobile vegetations on the aortic valve
      and severe aortic regurgitation. Aortic valve replacement was performed to
      prevent septic embolism and deterioration of congestive heart failure. The
      empiric therapy with vancomycin, ampicillin, and gentamycin was initiated because
      a pathogen was not identified. But Erysipelothrix rhusiopathiae (gram-positive
      rod) was isolated on the 4th day after surgery. The target therapy with
      penicillin G and clindamycin was started and continued for 4 weeks after surgery.
      The inflammatory parameters improved steadily and the patient was discharged on
      the 36th day after surgery. Infective endocarditis due to gram-positive rods can
      be easily mistaken for streptococci or dismissed as a skin contamination. But, E.
      rhusiopathiae endocarditis should be considered in the differential diagnosis.

PMID- 22664948
TI  - A case of bilateral multiple pulmonary chondroma: necessity of follow-up for
      Carney's triad.
AB  - We report a case of pulmonary bilateral multiple chondromas that were possibly an
      initial clinical presentation of Carney's triad. A 56-year-old Japanese non
      smoking asymptomatic woman was admitted to the hospital for further examination
      of small, multiple, bilateral nodules in the lungs. Although chest radiological
      findings suggested that the nodules were possibly metastatic pulmonary tumors,
      the malignant origin was not detected. During diagnostic video-assisted thoracic
      surgery, wedge resections including the nodules were performed. Since
      pathological examination showed nodules were surrounded by fibrous and
      eosinophilic stroma, we diagnose the nodules as chondromas. These chondromas were
      possibly components of Carney's triad, because each nodule had a thin fibrous
      pseudocapsule and did not have an entrapped epithelium and fat. Some patients die
      of Carney's triad because of malignant alteration of lesions. Therefore, the
      patients with Carney's triad should be taken a medical check periodically. This
      patient was scheduled to undergo the check-up for several years.

PMID- 22664949
TI  - Reducing death from cancer: what will it take?
AB  - In spite of advances in cancer diagnosis and treatment, cancer remains a serious
      problem for most societies. It is unlikely that cancer can ever be eliminated
      entirely; therefore, we must continue to seek ways to reduce the incidence,
      morbidity, and mortality from this devastating disease. Although most cancer
      research is devoted to finding new treatments, there are many other obstacles to
      reducing death from cancer that will need to be addressed if significant progress
      is to be made. These include growth in the number of cancer cases owing to the
      increasing longevity of populations, unequal access to cancer care, the
      increasing number of cancer survivors, limited resources including human
      resources, and our inability to deal with preventable cancers. To address these
      challenges, we must make cancer a national and international priority. We must
      focus our attention on prevention, not just on treatment, including elimination
      of tobacco use and reduction in exposure to environmental carcinogens. Finally,
      we must improve the accessibility of cancer care and ensure that there will be
      new generations of oncologists, health-care providers, and biomedical researchers
      by investing in medical research and education.

PMID- 22664950
TI  - Correlation of the risk of breast cancer and disruption of the circadian rhythm
      (Review).
AB  - Breast cancer is the worldwide leading cause of cancer incidence among women.
      Night shift work exposure has been recently considered one of the significant
      breast cancer risk factors in industrialized countries. The mechanisms by which
      this work exposure may be responsible for cancer development is still discussed.
      In the last 15 years, many authors have paid attention to the relationship
      between night shift work and breast cancer risk. In the current study, eight case
      control studies and four prospective epidemiological studies describing such
      relationship are discussed. A positive correlation between night shift work and
      breast cancer risk was described in 8 out of 12 studies. However, different
      reasons suggest that some of these studies have an Achilles heel according to the
      International Agency of Cancer (IARC) indications. Both the circadian system
      alteration and the melatonin output reduction, related to the exposure to light
      at-night during night shift work, remain the most valid hypotheses on the causal
      relation of shift work and breast cancer. Overall, the results of the present
      study suggest that there is an association between night shift work and breast
      cancer development in western countries. However, further studies are needed to
      confirm such association and to understand which biomolecular mechanisms may be
      involved in the pathogenesis of cancer diagnosed in patients with night shift
      work exposure.

PMID- 22664952
TI  - The continuing quest for effective early interventions.

PMID- 22664951
TI  - Chemotherapy with bevacizumab for metastatic colorectal cancer: a retrospective
      review of 181 Japanese patients.
AB  - BACKGROUND: There has so far been little information on the clinical effect of
      bevacizumab against colorectal cancer in Japan. Hence, this study was conducted
      to retrospectively evaluate the safety and efficacy of bevacizumab in clinical
      practice. METHODS: A total of 181 patients with metastatic colorectal cancer
      (mCRC) received bevacizumab in combination with chemotherapy at 18 hospitals in
      Kumamoto prefecture, Japan. We surveyed the medical records of all patients
      regarding the patient characteristics, objective tumor responses, and adverse
      events. We analyzed their overall survival and the survival benefit when
      continuing the administration of bevacizumab beyond disease progression
      (progressive disease; PD) in patients who received bevacizumab-containing 1st
      line therapy. RESULTS: The response rate (RR) in all lines of therapy was 42 %.
      The 1st line patients showed significantly better survival in comparison to the
      patients who received further lines of treatment (P = 0.005). There were no
      significant differences in survival between the group with post-PD treatment with
      bevacizumab and the group with post-PD treatment without bevacizumab (P = 0.13).
      The most common grade 3 or greater adverse event associated with bevacizumab was
      hypertension (12.2 %). Especially, a high incidence of gastrointestinal (GI)
      perforation was shown in this study (4.4 %) and most of the patients with GI
      perforation had some risk factors for this complication. CONCLUSION: Although the
      survival benefit of bevacizumab in Japanese patients with mCRC was similar to
      that observed in previous clinical trials, this study showed a high incidence of
      GI perforation in comparison to previous studies. Therefore, the careful
      selection of patients with few risk factors for this complication is likely to
      lead to a greater benefit from bevacizumab treatment.

PMID- 22664953
TI  - MicroRNA-1 and microRNA-499 downregulate the expression of the ets1 proto
      oncogene in HepG2 cells.
AB  - MicroRNAs may function to promote or suppress tumor development, depending on the
      cellular context. The important role of microRNAs in regulating molecular
      pathways underlying tumorigenesis has been emphasized in hepatocellular carcinoma
      (HCC). MicroRNAs regulate gene expression via post-transcriptional mechanisms by
      inhibiting translation or by degrading mRNA. In this study, we show that microRNA
      1 (miR-1) and microRNA-499 (miR-499) are capable of repressing the expression of
      the ets1 proto-oncogene, which plays a fundamental role in the extracellular
      matrix (ECM) degradation, a process required for tumor cell invasion and
      migration. We used luciferase reporter assays to demonstrate that miR-1 and miR
      499 target the 3' untranslated region (UTR) of ets1. Overexpression of miR-1 and
      miR-499 in HepG2 cells led to downregulation of ets1 mRNA and protein as assessed
      by quantitative reverse transcription PCR and western blot analysis. Furthermore,
      overexpression of miR-1 and miR-499 inhibited the invasion and migration of HepG2
      cells in matrigel invasion and transwell migration assays, respectively. These
      results suggest that miR-1 and miR-499 may play an important role in the
      pathogenesis of HCC by regulating ets1.

PMID- 22664954
TI  - Comparative effectiveness of rhythm control vs rate control drug treatment effect
      on mortality in patients with atrial fibrillation.
AB  - BACKGROUND: Controversy continues concerning the choice of rhythm control vs rate
      control treatment strategies for atrial fibrillation (AF). A recent clinical
      trial showed no difference in 5-year mortality between the 2 treatments. We aimed
      to determine whether the 2 strategies have similar effectiveness when applied to
      a general population of patients with AF with longer follow-up. METHODS: We used
      population-based administrative databases from Quebec, Canada, from 1999 to 2007
      to select patients 66 years or older hospitalized with an AF diagnosis who did
      not have AF-related drug prescriptions in the year before the admission but
      received a prescription within 7 days of discharge. Patients were followed until
      death or administrative censoring. Mortality was analyzed by multivariable Cox
      regression. RESULTS: Among 26,130 patients followed for a mean (SD) period of 3.1
      years (2.3 years), there were 13,237 deaths (49.5%). After adjusting for
      covariates, we found that the effect of rhythm vs rate control drugs changed over
      time: after a small increase in mortality for patients treated with rhythm
      control in the 6 months following treatment initiation (hazard ratio [HR], 1.07;
      95% CI, 1.01-1.14), the mortality was similar between the 2 groups until year 4
      but decreased steadily in the rhythm control group after year 5 (HR, 0.89; 95%
      CI, 0.81-0.96; and HR, 0.77; 95% CI, 0.62-0.95, after 5 and 8 years,
      respectively). CONCLUSIONS: In this population-based sample of patients with AF,
      we found little difference in mortality within 4 years of treatment initiation
      between patients with AF initiating rhythm control therapy vs those initiating
      rate control therapy. However, rhythm control therapy seems to be superior in the
      long-term.

PMID- 22664955
TI  - Transient receptor potential vanilloid 1 activation enhances gut glucagon-like
      peptide-1 secretion and improves glucose homeostasis.
AB  - Type 2 diabetes mellitus (T2DM) is rapidly prevailing as a serious global health
      problem. Current treatments for T2DM may cause side effects, thus highlighting
      the need for newer and safer therapies. We tested the hypothesis that dietary
      capsaicin regulates glucose homeostasis through the activation of transient
      receptor potential vanilloid 1 (TRPV1)-mediated glucagon-like peptide-1 (GLP-1)
      secretion in the intestinal cells and tissues. Wild-type (WT) and TRPV1 knockout
      (TRPV1(-/-)) mice were fed dietary capsaicin for 24 weeks. TRPV1 was localized in
      secretin tumor cell-1 (STC-1) cells and ileum. Capsaicin stimulated GLP-1
      secretion from STC-1 cells in a calcium-dependent manner through TRPV1
      activation. Acute capsaicin administration by gastric gavage increased GLP-1 and
      insulin secretion in vivo in WT but not in TRPV1(-/-) mice. Furthermore, chronic
      dietary capsaicin not only improved glucose tolerance and increased insulin
      levels but also lowered daily blood glucose profiles and increased plasma GLP-1
      levels in WT mice. However, this effect was absent in TRPV1(-/-) mice. In db/db
      mice, TRPV1 activation by dietary capsaicin ameliorated abnormal glucose
      homeostasis and increased GLP-1 levels in the plasma and ileum. The present
      findings suggest that TRPV1 activation-stimulated GLP-1 secretion could be a
      promising approach for the intervention of diabetes.

PMID- 22664956
TI  - Neuroadrenergic dysfunction along the diabetes continuum: a comparative study in
      obese metabolic syndrome subjects.
AB  - Neuroadrenergic function in type 2 diabetic (T2D) patients without neuropathy is
      poorly characterized. We therefore compared sympathetic nervous system activity
      at rest and during an oral glucose tolerance test in obese metabolic syndrome
      (MetS) subjects classified as glucose intolerant (impaired glucose tolerance
      [IGT]; n = 17) or treatment-naive T2D (n = 17). Untreated subjects, matched for
      age (mean 59 +/- 1 year), sex, BMI (32.4 +/- 0.6 kg/m(2)), and family history of
      diabetes were studied. We measured resting muscle sympathetic nerve activity
      (MSNA) by microneurography, whole-body norepinephrine kinetics by isotope
      dilution, insulin sensitivity by euglycemic-hyperinsulinemic clamp (steady-state
      glucose utilization adjusted for fat-free mass and steady-state insulin
      concentration [M/I]), and MetS components. T2D subjects had higher resting MSNA
      burst incidence (67 +/- 4 versus 55 +/- 3 bursts per 100 heartbeats; P = 0.05)
      and arterial norepinephrine levels (264 +/- 33 versus 167 +/- 16 pg/mL; P =
      0.02), lower plasma norepinephrine clearance (by 17%; P = 0.03), and reduced
      neuronal reuptake compared with IGT subjects (by 46%; P = 0.04). Moreover,
      norepinephrine spillover responses to glucose ingestion were blunted in T2D
      subjects. The M/I value independently predicted whole-body norepinephrine
      spillover (r = -0.47; P = 0.008), whereas fasting insulin level related to
      neuronal norepinephrine reuptake (r = -0.35, P = 0.047). These findings
      demonstrate that progression to T2D is associated with increased central
      sympathetic drive, blunted sympathetic responsiveness, and altered norepinephrine
      disposition.

PMID- 22664957
TI  - Resting-state brain functional connectivity is altered in type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD).
      Populations at risk for AD show altered brain activity in the default mode
      network (DMN) before cognitive dysfunction. We evaluated this brain pattern in
      T2DM patients. We compared T2DM patients (n = 10, age = 56 +/- 2.2 years, fasting
      plasma glucose [FPG] = 8.4 +/- 1.3 mmol/L, HbA(1c) = 7.5 +/- 0.54%) with
      nondiabetic age-matched control subjects (n = 11, age = 54 +/- 1.8 years, FPG =
      4.8 +/- 0.2 mmol/L) using resting-state functional magnetic resonance imaging to
      evaluate functional connectivity strength among DMN regions. We also evaluated
      hippocampal volume, cognition, and insulin sensitivity by homeostasis model
      assessment of insulin resistance (HOMA-IR). Control subjects showed stronger
      correlations versus T2DM patients in the DMN between the seed (posterior
      cingulate) and bilateral middle temporal gyrus (beta = 0.67 vs. 0.43), the right
      inferior and left medial frontal gyri (beta = 0.75 vs. 0.54), and the left
      thalamus (beta = 0.59 vs. 0.37), respectively, with no group differences in
      cognition or hippocampal size. In T2DM patients, HOMA-IR was inversely correlated
      with functional connectivity in the right inferior frontal gyrus and precuneus.
      T2DM patients showed reduced functional connectivity in the DMN compared with
      control subjects, which was associated with insulin resistance in selected brain
      regions, but there were no group effects of brain structure or cognition.

PMID- 22664959
TI  - Best practices for heart failure: a focused review.
AB  - Heart failure (HF) is a progressive condition and is associated with high patient
      mortality rates and frequent hospitalizations. This article provides an overview
      of clinical, self-management support, and care transitions best practices for HF
      care in the home care sector. Clinicians armed with competencies in HF management
      are positioned to meet the 3-part aim of healthcare reform: improved health,
      better care, and lower cost.

PMID- 22664960
TI  - Resources for Middle Eastern patients: online resources for culturally and
      linguistically appropriate services in home healthcare and hospice, part 3.
AB  - As the population of patients for whom English is not their primary language
      grows, home care and hospice clinicians are challenged to provide culturally
      respectful and acceptable patient-centered care for cultures and languages
      unfamiliar to them. This article identifies resources for understanding the
      culture of Middle Eastern-born patients and appropriate patient education
      materials in most of the languages spoken by this population. The resources have
      been made available for free on the Web by healthcare professionals, government
      agencies, and support organizations from around the world.

PMID- 22664958
TI  - Heterogeneous nuclear ribonucleoprotein F suppresses angiotensinogen gene
      expression and attenuates hypertension and kidney injury in diabetic mice.
AB  - We investigated the impact of heterogeneous nuclear ribonucleoprotein F (hnRNP F)
      overexpression on angiotensinogen (Agt) gene expression, hypertension, and renal
      proximal tubular cell (RPTC) injury in high-glucose milieu both in vivo and in
      vitro. Diabetic Akita transgenic (Tg) mice specifically overexpressing hnRNP F in
      their RPTCs were created, and the effects on systemic hypertension, Agt gene
      expression, renal hypertrophy, and interstitial fibrosis were studied. We also
      examined immortalized rat RPTCs stably transfected with control plasmid or
      plasmid containing hnRNP F cDNA in vitro. The results showed that hnRNP F
      overexpression attenuated systemic hypertension, suppressed Agt and transforming
      growth factor-beta1 (TGF-beta1) gene expression, and reduced urinary Agt and
      angiotensin II levels, renal hypertrophy, and glomerulotubular fibrosis in Akita
      hnRNP F-Tg mice. In vitro, hnRNP F overexpression prevented the high-glucose
      stimulation of Agt and TGF-beta1 mRNA expression and cellular hypertrophy in
      RPTCs. These data suggest that hnRNP F plays a modulatory role and can ameliorate
      hypertension, renal hypertrophy, and interstitial fibrosis in diabetes. The
      underlying mechanism is mediated, at least in part, via the suppression of
      intrarenal Agt gene expression in vivo. hnRNP F may be a potential target in the
      treatment of hypertension and kidney injury in diabetes.

PMID- 22664961
TI  - Putative tumor metastasis-associated genes in human gastric cancer.
AB  - Gastric cancer is one of the leading causes of cancer mortality and its
      malignancy, resulting from disseminated cancer cells of diffuse type, is
      clinically manifested as metastases to the liver and peritoneum. The aim of the
      present study was to identify putative tumor metastasis-associated genes in human
      gastric cancer cells of diffuse type. An MKN45 cell line constitutively
      expressing green fluorescent protein (MKN45-GFP) was established and selected
      using the Transwell(r) system for invasive sublines MKN45-GFP-4, MKN45-GFP-10 and
      MKN45-GFP-12. MKN45-GFP-10 and MKN45-GFP-12 are highly invasive compared to the
      others. The mRNA levels were measured with cDNA microarrays and correlated with
      their invasion abilities in these sublines. Many of the genes identified with a
      positive or negative correlation are associated with angiogenesis, cell cycle,
      cytoskeleton and cell motility, protease and cell adhesion, as well as cellular
      signal transduction. In particular, novel genes without known functions were also
      noted. RT-PCR and western blot analyses were applied to verify the expression of
      selective genes. Following orthotopical intraperitoneal implantation, MKN45-GFP
      12 demonstrated significantly higher in vivo tumor malignancies than parental
      MKN45-GFP in ascites induction and liver -invasion in mice. We have identified
      putative gastric tumor metastasis-associated, as well as novel genes. These genes
      and their protein products are to be further explored for their functional roles
      associated with tumor metastasis. The molecular profiles of these identified
      genes, gene transcripts and proteins in the patient specimens are likely to be
      useful biomarkers for diagnostic, therapeutic and/or prognostics. Most
      importantly, they may be used as molecular targets for the discovery of antitumor
      drugs against human gastric cancer metastasis.

PMID- 22664962
TI  - Production of lentiviral vectors for transducing cells from the central nervous
      system.
AB  - Efficient gene delivery in the central nervous system (CNS) is important in
      studying gene functions, modeling neurological diseases and developing
      therapeutic approaches. Lentiviral vectors are attractive tools in transduction
      of neurons and other cell types in CNS as they transduce both dividing and non
      dividing cells, support sustained expression of transgenes, and have relatively
      large packaging capacity and low toxicity. Lentiviral vectors have been
      successfully used in transducing many neural cell types in vitro and in animals.
      Great efforts have been made to develop lentiviral vectors with improved
      biosafety and efficiency for gene delivery. The current third generation
      replication-defective and self-inactivating (SIN) lentiviral vectors are depicted
      in Figure 1. The required elements for vector packaging are split into four
      plasmids. In the lentiviral transfer plasmid, the U3 region in the 5' long
      terminal repeat (LTR) is replaced with a strong promoter from another virus. This
      modification allows the transcription of the vector sequence independent of HIV-1
      Tat protein that is normally required for HIV gene expression. The packaging
      signal (Psi) is essential for encapsidation and the Rev-responsive element (RRE)
      is required for producing high titer vectors. The central polypurine tract (cPPT)
      is important for nuclear import of the vector DNA, a feature required for
      transducing non-dividing cells. In the 3' LTR, the cis-regulatory sequences are
      completely removed from the U3 region. This deletion is copied to 5' LTR after
      reverse transcription, resulting in transcriptional inactivation of both LTRs.
      Plasmid pMDLg/pRRE contains HIV-1 gag/pol genes, which provide structural
      proteins and reverse transcriptase. pRSV-Rev encodes Rev which binds to the RRE
      for efficient RNA export from the nucleus. pCMV-G encodes the vesicular
      stomatitis virus glycoprotein (VSV-G) that replaces HIV-1 Env. VSV-G expands the
      tropism of the vectors and allows concentration via ultracentrifugation. All the
      genes encoding the accessory proteins, including Vif, Vpr, Vpu, and Nef are
      excluded in the packaging system. The production and manipulation of lentiviral
      vectors should be carried out according to NIH guidelines for research involving
      recombinant DNA (http://oba.od.nih.gov/oba/rac/Guidelines/NIH_Guidelines.pdf). An
      approval from individual Institutional Biological and Chemical Safety Committee
      may be required before using lentiviral vectors. Lentiviral vectors are commonly
      produced by cotransfection of 293T cells with lentiviral transfer plasmid and the
      helper plasmids encoding the proteins required for vector packaging. Many
      lentiviral transfer plasmids and helper plasmids can be obtained from Addgene, a
      non-profit plasmid repository (http://www.addgene.org/). Some stable packaging
      cell lines have been developed, but these systems provide less flexibility and
      their packaging efficiency generally declines over time. Commercially available
      transfection kits may support high efficiency of transfection, but they can be
      very expensive for large scale vector preparations. Calcium phosphate
      precipitation methods provide highly efficient transfection of 293T cells and
      thus provide a reliable and cost effective approach for lentiviral vector
      production. In this protocol, we produce lentiviral vectors by cotransfection of
      293T cells with four plasmids based on the calcium phosphate precipitation
      principle, followed by purification and concentration with ultracentrifugation
      through a 20% sucrose cushion. The vector titers are determined by fluorescence-
      activated cell sorting (FACS) analysis or by real time qPCR. The production and
      titration of lentiviral vectors in this protocol can be finished with 9 days. We
      provide an example of transducing these vectors into murine neocortical cultures
      containing both neurons and astrocytes. We demonstrate that lentiviral vectors
      support high efficiency of transduction and cell type-specific gene expression in
      primary cultured cells from CNS.

PMID- 22664963
TI  - Hyperimmune bovine colostrum as a low-cost, large-scale source of antibodies with
      broad neutralizing activity for HIV-1 envelope with potential use in
      microbicides.
AB  - Bovine colostrum (first milk) contains very high concentrations of IgG, and on
      average 1 kg (500 g/liter) of IgG can be harvested from each immunized cow
      immediately after calving. We used a modified vaccination strategy together with
      established production systems from the dairy food industry for the large-scale
      manufacture of broadly neutralizing HIV-1 IgG. This approach provides a low-cost
      mucosal HIV preventive agent potentially suitable for a topical microbicide. Four
      cows were vaccinated pre- and/or postconception with recombinant HIV-1 gp140
      envelope (Env) oligomers of clade B or A, B, and C. Colostrum and purified
      colostrum IgG were assessed for cross-clade binding and neutralization against a
      panel of 27 Env-pseudotyped reporter viruses. Vaccination elicited high anti
      gp140 IgG titers in serum and colostrum with reciprocal endpoint titers of up to
      1 * 10(5). While nonimmune colostrum showed some intrinsic neutralizing activity,
      colostrum from 2 cows receiving a longer-duration vaccination regimen
      demonstrated broad HIV-1-neutralizing activity. Colostrum-purified polyclonal IgG
      retained gp140 reactivity and neutralization activity and blocked the binding of
      the b12 monoclonal antibody to gp140, showing specificity for the CD4 binding
      site. Colostrum-derived anti-HIV antibodies offer a cost-effective option for
      preparing the substantial quantities of broadly neutralizing antibodies that
      would be needed in a low-cost topical combination HIV-1 microbicide.

PMID- 22664965
TI  - Plasmid-mediated quinolone resistance in extended-spectrum-beta-lactamase- and
      AmpC beta-lactamase-producing Serratia marcescens in China.
AB  - We investigated the prevalence of plasmid-mediated quinolone resistance (PMQR)
      determinants and examined the association of these determinants with extended
      spectrum beta-lactamases (ESBLs) and/or plasmid-mediated AmpC beta-lactamases
      (pAmpCs) in Serratia marcescens isolates in China. In this study, the presence of
      PMQR determinants was significantly related to the coproduction of ESBLs and/or
      pAmpCs (CTX-M-14, SHV-5, DHA-1, and ACT-1), among which CTX-M-14 was the most
      common gene type.

PMID- 22664964
TI  - Dose-ranging comparison of rifampin and rifapentine in two pathologically
      distinct murine models of tuberculosis.
AB  - In previous experiments, replacing the 10-mg/kg of body weight daily dose of
      rifampin with 7.5 to 10 mg/kg of rifapentine in combinations containing isoniazid
      and pyrazinamide reduced the duration of treatment needed to cure tuberculosis in
      BALB/c mice by approximately 50% due to rifapentine's more potent activity and
      greater drug exposures obtained. In the present study, we performed dose-ranging
      comparisons of the bactericidal and sterilizing activities of rifampin and
      rifapentine, alone and in combination with isoniazid and pyrazinamide with or
      without ethambutol, in BALB/c mice and in C3HeB/FeJ mice, which develop necrotic
      lung granulomas after infection with Mycobacterium tuberculosis. Each rifamycin
      demonstrated a significant increase in sterilizing activity with increasing dose.
      Rifapentine was roughly 4 times more potent in both mouse strains. These results
      reinforce the rationale for ongoing clinical trials to ascertain the highest well
      tolerated doses of rifampin and rifapentine. This study also provides an
      important benchmark for the efficacy of the first-line regimen in C3HeB/FeJ mice,
      a strain in which the lung lesions observed after M. tuberculosis infection may
      better represent the pathology of human tuberculosis.

PMID- 22664966
TI  - Effect of sodium fluoride, ampicillin, and chlorhexidine on Streptococcus mutans
      biofilm detachment.
AB  - We examined the effect of three clinically used antimicrobials on Streptococcus
      mutans UA159 biofilm detachment under flow conditions. Sodium fluoride (NaF) and
      chlorhexidine at MIC levels promoted biofilm detachment and inhibited detachment
      when concentrations were higher than the MIC and reduced detached-cell viability
      only at high concentrations. Ampicillin at all concentrations tested inhibited
      detachment and reduced the percentage of viable biofilm-detached cells. All the
      three antimicrobial treatments reduced biofilm live/dead cell ratios.

PMID- 22664967
TI  - Inhibition of biofilm formation by esomeprazole in Pseudomonas aeruginosa and
      Staphylococcus aureus.
AB  - Staphylococcus aureus and Pseudomonas aeruginosa are common nosocomial pathogens
      responsible for biofilm-associated infections. Proton pump inhibitors (PPI), such
      as esomeprazole, may have novel antimicrobial properties. The objective of this
      study was to assess whether esomeprazole prevents sessile bacterial growth and
      biofilm formation and whether it may have synergistic killing effects with
      standard antibiotics. The antibiofilm activity of esomeprazole at 0.25 mM was
      tested against two strains each of S. aureus and P. aeruginosa. Bacterial
      biofilms were prepared using a commercially available 96-peg-plate Calgary
      biofilm device. Sessile bacterial CFU counts and biomass were assessed during 72
      hours of esomeprazole exposure. The killing activities after an additional 24
      hours of vancomycin (against S. aureus) and meropenem (against P. aeruginosa)
      treatment with or without preexposure to esomeprazole were also assessed by CFU
      and biomass analyses. P. aeruginosa and S. aureus strains exposed to esomeprazole
      displayed decreased sessile bacterial growth and biomass (P < 0.001, each
      parameter). After 72 h of exposure, there was a 1-log(10) decrease in the CFU/ml
      of esomeprazole-exposed P. aeruginosa and S. aureus strains compared to controls
      (P < 0.001). After 72 h of exposure, measured absorbance was 100% greater in P.
      aeruginosa control strains than in esomeprazole-exposed strains (P < 0.001).
      Increased killing and decreased biomass were observed for esomeprazole-treated
      bacteria compared to untreated controls exposed to conventional antibiotics (P <
      0.001, each parameter). Reduced biofilm growth after 24 h was visibly apparent by
      light micrographs for P. aeruginosa and S. aureus isolates exposed to
      esomeprazole compared to untreated controls. In conclusion, esomeprazole
      demonstrated an antibiofilm effect against biofilm-producing S. aureus and P.
      aeruginosa.

PMID- 22664968
TI  - Crystal structure of the mobile metallo-beta-lactamase AIM-1 from Pseudomonas
      aeruginosa: insights into antibiotic binding and the role of Gln157.
AB  - Metallo-beta-lactamase (MBL) genes confer resistance to virtually all beta-lactam
      antibiotics and are rapidly disseminated by mobile genetic elements in Gram
      negative bacteria. MBLs belong to three different subgroups, B1, B2, and B3, with
      the mobile MBLs largely confined to subgroup B1. The B3 MBLs are a divergent
      subgroup of predominantly chromosomally encoded enzymes. AIM-1 (Adelaide
      IMipenmase 1) from Pseudomonas aeruginosa was the first B3 MBL to be identified
      on a readily mobile genetic element. Here we present the crystal structure of AIM
      1 and use in silico docking and quantum mechanics and molecular mechanics (QM/MM)
      calculations, together with site-directed mutagenesis, to investigate its
      interaction with beta-lactams. AIM-1 adopts the characteristic
      alphabeta/betaalpha sandwich fold of MBLs but differs from other B3 enzymes in
      the conformation of an active site loop (residues 156 to 162) which is involved
      both in disulfide bond formation and, we suggest, interaction with substrates.
      The structure, together with docking and QM/MM calculations, indicates that the
      AIM-1 substrate binding site is narrower and more restricted than those of other
      B3 MBLs, possibly explaining its higher catalytic efficiency. The location of
      Gln157 adjacent to the AIM-1 zinc center suggests a role in drug binding that is
      supported by our in silico studies. However, replacement of this residue by
      either Asn or Ala resulted in only modest reductions in AIM-1 activity against
      the majority of beta-lactam substrates, indicating that this function is
      nonessential. Our study reveals AIM-1 to be a subclass B3 MBL with novel
      structural and mechanistic features.

PMID- 22664970
TI  - Correlation between mutations in liaFSR of Enterococcus faecium and MIC of
      daptomycin: revisiting daptomycin breakpoints.
AB  - Mutations in liaFSR, a three-component regulatory system controlling cell
      envelope stress response, were recently linked with the emergence of daptomycin
      (DAP) resistance in enterococci. Our previous work showed that a liaF mutation
      increased the DAP MIC of a vancomycin-resistant Enterococcus faecalis strain from
      1 to 3 MUg/ml (the DAP breakpoint is 4 MUg/ml), suggesting that mutations in the
      liaFSR system could be a pivotal initial event in the development of DAP
      resistance. With the hypothesis that clinical enterococcal isolates with DAP MICs
      between 3 and 4 MUg/ml might harbor mutations in liaFSR, we studied 38
      Enterococcus faecium bloodstream isolates, of which 8 had DAP MICs between 3 and
      4 MUg/ml by Etest in Mueller-Hinton agar. Interestingly, 6 of these 8 isolates
      had predicted amino acid changes in the LiaFSR system. Moreover, we previously
      showed that among 6 DAP-resistant E. faecium isolates (MICs of >4 MUg/ml), 5 had
      mutations in liaFSR. In contrast, none of 16 E. faecium isolates with a DAP MIC
      of <=2 MUg/ml harbored mutations in this system (P < 0.0001). All but one isolate
      with liaFSR changes exhibited DAP MICs of >=16 MUg/ml by Etest using brain heart
      infusion agar (BHIA), a medium that better supports enterococcal growth. Our
      findings provide a strong association between DAP MICs within the upper
      susceptibility range and mutations in the liaFSR system. Concomitant
      susceptibility testing on BHIA may be useful for identifying these E. faecium
      first-step mutants. Our results also suggest that the current DAP breakpoint for
      E. faecium may need to be reevaluated.

PMID- 22664971
TI  - Influence of DNA template choice on transcription and inhibition of Escherichia
      coli RNA polymerase.
AB  - In recent decades, quantitative transcription assays using bacterial RNA
      polymerase (RNAP) have been performed under widely diverse experimental
      conditions. We demonstrate that the template choice can influence the inhibitory
      potency of RNAP inhibitors. Furthermore, we illustrate that the sigma factor
      (sigma(70)) surprisingly increases the transcription efficiency of templates with
      nonphysiological nonprokaryotic promoters. Our results might be a useful
      guideline in the early stages of using RNAP for drug discovery.

PMID- 22664972
TI  - High frequency of IMP-6 among clinical isolates of metallo-beta-lactamase
      producing Escherichia coli in Japan.

PMID- 22664973
TI  - Panel of prototypical recombinant infectious molecular clones resistant to
      nevirapine, efavirenz, etravirine, and rilpivirine.
AB  - We created a panel of 10 representative multi-nonnucleoside reverse transcriptase
      inhibitor (NNRTI)-resistant recombinant infectious molecular HIV-1 clones to
      assist researchers studying NNRTI resistance or developing novel NNRTIs. The
      cloned viruses contain most of the major NNRTI resistance mutations and most of
      the significantly associated mutation pairs that we identified in two network
      analyses. Each virus in the panel has intermediate- or high-level resistance to
      all or three of the four most commonly used NNRTIs.

PMID- 22664969
TI  - Development of anti-infectives using phage display: biological agents against
      bacteria, viruses, and parasites.
AB  - The vast majority of anti-infective therapeutics on the market or in development
      are small molecules; however, there is now a nascent pipeline of biological
      agents in development. Until recently, phage display technologies were used
      mainly to produce monoclonal antibodies (MAbs) targeted against cancer or
      inflammatory disease targets. Patent disputes impeded broad use of these methods
      and contributed to the dearth of candidates in the clinic during the 1990s.
      Today, however, phage display is recognized as a powerful tool for selecting
      novel peptides and antibodies that can bind to a wide range of antigens, ranging
      from whole cells to proteins and lipid targets. In this review, we highlight
      research that exploits phage display technology as a means of discovering novel
      therapeutics against infectious diseases, with a focus on antimicrobial peptides
      and antibodies in clinical or preclinical development. We discuss the different
      strategies and methods used to derive, select, and develop anti-infectives from
      phage display libraries and then highlight case studies of drug candidates in the
      process of development and commercialization. Advances in screening,
      manufacturing, and humanization technologies now mean that phage display can make
      a significant contribution in the fight against clinically important pathogens.

PMID- 22664974
TI  - Saquinavir inhibits early events associated with establishment of HIV-1
      infection: potential role for protease inhibitors in prevention.
AB  - The maturation of newly formed human immunodeficiency virus type 1 (HIV-1)
      virions is a critical step for the establishment of productive infection. We
      investigated the potential of saquinavir (SQV), a protease inhibitor (PI) used in
      highly active antiretroviral therapy (HAART), as a candidate microbicide. SQV
      inhibited replication of clade B and clade C isolates in a dose-dependent manner
      in all cellular models tested: PM-1 CD4 T cells, peripheral blood mononuclear
      cells (PBMCs), monocyte-derived macrophages (MDMs), and immature monocyte-derived
      dendritic cells (iMDDCs). SQV also inhibited production of infectious virus in
      cervical, penile, and colorectal explants cocultured with T cells. Moreover, SQV
      demonstrated inhibitory potency against trans infection of T cells by in vitro
      derived dendritic cells and by primary dendritic cells that emigrate from penile
      and cervical tissue explants. No cellular or tissue toxicity was detected in the
      presence of SQV, suggesting that this drug could be considered for development as
      a component of an effective microbicide, capable of blocking viral maturation and
      transmission of HIV-1 at mucosal surfaces.

PMID- 22664975
TI  - Small-molecule inhibitors of the LEDGF/p75 binding site of integrase block HIV
      replication and modulate integrase multimerization.
AB  - Targeting the HIV integrase (HIV IN) is a clinically validated approach for
      designing novel anti-HIV therapies. We have previously described the discovery of
      a novel class of integration inhibitors, 2-(quinolin-3-yl)acetic acid
      derivatives, blocking HIV replication at a low micromolar concentration through
      binding in the LEDGF/p75 binding pocket of HIV integrase, hence referred to as
      LEDGINs. Here we report the detailed characterization of their mode of action.
      The design of novel and more potent analogues with nanomolar activity enabled
      full virological evaluation and a profound mechanistic study. As allosteric
      inhibitors, LEDGINs bind to the LEDGF/p75 binding pocket in integrase, thereby
      blocking the interaction with LEDGF/p75 and interfering indirectly with the
      catalytic activity of integrase. Detailed mechanism-of-action studies reveal that
      the allosteric mode of inhibition is likely caused by an effect on HIV-1
      integrase oligomerization. The multimodal inhibition by LEDGINs results in a
      block in HIV integration and in a replication deficiency of progeny virus. The
      allosteric nature of LEDGINs leads to synergy in combination with the clinically
      approved active site HIV IN strand transfer inhibitor (INSTI) raltegravir, and
      cross-resistance profiling proves the distinct mode of action of LEDGINs and
      INSTIs. The allosteric nature of inhibition and compatibility with INSTIs
      underline an interest in further (clinical) development of LEDGINs.

PMID- 22664976
TI  - First-in-human study of the pharmacokinetics and antiviral activity of IDX375, a
      novel nonnucleoside hepatitis C virus polymerase inhibitor.
AB  - IDX375 is a potent and selective palm-binding nonnucleoside inhibitor of the
      hepatitis C virus (HCV) genotype 1 polymerase. This first-in-human study
      evaluated the safety, tolerability, and pharmacokinetics of IDX375 in healthy
      volunteers, as well as its antiviral activity in HCV-infected patients. IDX375,
      as a choline salt, was administered for 1 day to 40 healthy male volunteers (25-
      to 200-mg IDX375-equivalent single ascending doses and a 200-mg twice-daily [BID]
      dose) and three patients chronically infected with HCV genotype 1 (200 mg BID
      only). IDX375 was well absorbed and well tolerated by all of the study
      participants. A single-day 200-mg BID dose resulted in exposure-related anti-HCV
      activity with maximal 0.5 to 1.1 log(10) reductions in plasma HCV RNA. These
      observations support further clinical investigations of IDX375.

PMID- 22664977
TI  - Therapeutic activity of intramuscular peramivir in mice infected with a
      recombinant influenza A/WSN/33 (H1N1) virus containing the H275Y neuraminidase
      mutation.
AB  - The therapeutic activity of intramuscular (IM) peramivir was evaluated in mice
      infected with a recombinant influenza A/WSN/33 virus containing the H275Y
      neuraminidase (NA) mutation known to confer oseltamivir resistance. Regimens
      consisted of single (90 mg/kg of body weight) or multiple (45 mg/kg daily for 5
      days) IM peramivir doses that were initiated 24 h or 48 h postinfection (p.i.).
      An oral oseltamivir regimen (1 or 10 mg/kg daily for 5 days) was used for
      comparison. Untreated animals had a mortality rate of 75% and showed a mean
      weight loss of 16.9% on day 5 p.i. When started at 24 h p.i., both peramivir
      regimens prevented mortality and significantly reduced weight loss (P < 0.001)
      and lung viral titers (LVT) (P < 0.001). A high dose (10 mg/kg) of oseltamivir
      initiated at 24 h p.i. also prevented mortality and significantly decreased
      weight loss (P < 0.05) and LVT (P < 0.001) compared to the untreated group
      results. In contrast, a low dose (1 mg/kg) of oseltamivir did not show any
      benefits. When started at 48 h p.i., both peramivir regimens prevented mortality
      and significantly reduced weight loss (P < 0.01) and LVT (P < 0.001) whereas low
      dose or high-dose oseltamivir regimens had no effect on mortality rates, body
      weight loss, and LVT. Our results show that single-dose and multiple-dose IM
      peramivir regimens retain clinical and virological activities against the A/H1N1
      H275Y variant despite some reduction in susceptibility when assessed in vitro
      using enzymatic assays. IM peramivir could constitute an alternative for
      treatment of oseltamivir-resistant A/H1N1 infections, although additional studies
      are warranted to support such a recommendation.

PMID- 22664978
TI  - Randomized study of the effect of local anesthetic volume and concentration on
      the duration of peripheral nerve blockade.
AB  - BACKGROUND AND OBJECTIVES: Ultrasound guidance reduces the required local
      anesthetic volume for successful peripheral nerve block, but it is unclear
      whether this influences block duration. We investigated the ropivacaine volume
      and concentration effect on interscalene block duration. METHODS: One hundred
      eighty-five patients were randomized to 5 ropivacaine volume/concentration
      combinations (0.75% 5, 10, and 20 mL; 0.375% 20 and 40 mL) administered
      preoperatively via an interscalene catheter before shoulder surgery under general
      anesthesia. An elastomeric ropivacaine infusion commenced at the onset of pain.
      Patients were questioned at 24 hours primarily for the primary outcome: time to
      first pain. Group 5 mL was excluded post hoc because of an unacceptably high
      block failure rate. Multivariate Cox regression was used to assess the effect of
      volume and concentration (each corrected for the other) on the primary outcome.
      RESULTS: Probability of pain as a function of time was associated with not only
      dose, but also volume corrected for concentration and concentration corrected for
      volume: hazard ratio (95% confidence interval) for dose = 0.992 (0.987-0.997) (P
      = 0.002), volume = 0.959 (0.937-0.982) (P = 0.001), concentration = 0.852 (0.743
      0.976) (P = 0.021). Increasing the volume of ropivacaine 0.375% from 10 to 40 mL
      was estimated to increase median (quartiles) block duration from 10.0 (9.5-11.5)
      to 15.0 (10.75-21) hours. Similarly, increasing the concentration of 20 mL
      ropivacaine from 0.375% to 0.75% was estimated to increase median (quartiles)
      block duration from 10.75 (9.75-14.0) to 13.75 (10.5-21.0) hours. CONCLUSIONS:
      Block duration is influenced by both local anesthetic volume and concentration, a
      finding of increasing relevance with the current trend to lower volumes for
      ultrasound-guided regional anesthesia.

PMID- 22664979
TI  - Intracerebral hemorrhage from cerebral venous thrombosis.
AB  - Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with the
      incidence of 0.5 % from all strokes. The clinical presentation with cerebral
      hemorrhage constitutes a diagnostic challenge. Approximately one- third of CVT
      patients developed intracerebral hemorrhage (ICH). Associated factors include
      older age, female sex, acute onset (48 h), headache, decreased level of
      consciousness, seizure, elevated blood pressure and papilledema. MRI and MR
      venogram is the most recommend diagnostic modality in CVT. Anticoagulation
      therapy is the most commonly accepted treatment even in patients with ICH related
      CVT. Mechanical thrombectomy/thrombolysis may be considered in patients with
      neurological deterioration despite intensive medical treatment. Intracerebral
      hemorrhage in the context of CVT is usually associated with poorer outcomes
      compared to CVT without ICH.

PMID- 22664980
TI  - Conflict of interest policies and disclosure requirements among European Society
      of Cardiology National Cardiovascular Journals.
AB  - Disclosure of potential conflicts of interest (COI) is used by biomedical
      journals to guarantee credibility and transparency of the scientific process. COI
      disclosure, however, is not systematically nor consistently dealt with by
      journals. Recent joint editorial efforts paved the way towards the implementation
      of uniform vehicles for COI disclosure. This paper provides a comprehensive
      editorial perspective on classical COI-related issues. New insights into current
      COI policies and practices among European Society of Cardiology national
      cardiovascular journals, as derived from a cross-sectional survey using a
      standardised questionnaire, are discussed.

PMID- 22664981
TI  - Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high
      fat-fed rats.
AB  - BACKGROUND: Lipoic acid (LA) is an antioxidant with antiobesity and antidiabetic
      properties. Adiponectin is an adipokine with potent anti-inflammatory and insulin
      sensitizing properties. AMP-activated protein kinase (AMPK) is a key enzyme
      involved in cellular energy homeostasis. Activation of AMPK has been considered
      as a target to reverse the metabolic abnormalities associated with obesity and
      type 2 diabetes. AIM OF THE STUDY: The aim of this study was to determine the
      effects of LA on AMPK phosphorylation and adiponectin production in adipose
      tissue of low-fat (control diet) and high-fat diet-fed rats. RESULTS: Dietary
      supplementation with LA reduced body weight and adiposity in control and high-fat
      fed rats. LA also reduced basal hyperinsulinemia as well as the homeostasis model
      assessment (HOMA) levels, an index of insulin resistance, in high-fat-fed rats,
      which was in part independent of their food intake lowering actions. Furthermore,
      AMPK phosphorylation was increased in white adipose tissue (WAT) from LA-treated
      rats as compared with pair-fed animals. Dietary supplementation with LA also
      upregulated adiponectin gene expression in WAT, while a negative correlation
      between adiposity-corrected adiponectin levels and HOMA index was found. Our
      present data suggest that the ability of LA supplementation to prevent insulin
      resistance in high-fat diet-fed rats might be related in part to the stimulation
      of AMPK and adiponectin in WAT.

PMID- 22664983
TI  - One core, two shells: bacterial and eukaryotic ribosomes.
AB  - Ribosomes are universally conserved enzymes that carry out protein biosynthesis.
      Bacterial and eukaryotic ribosomes, which share an evolutionarily conserved core,
      are thought to have evolved from a common ancestor by addition of proteins and
      RNA that bestow different functionalities to ribosomes from different domains of
      life. Recently, structures of the eukaryotic ribosome, determined by X-ray
      crystallography, have allowed us to compare these structures to previously
      determined structures of bacterial ribosomes. Here we describe selected bacteria-
      or eukaryote-specific structural features of the ribosome and discuss the
      functional implications of some of them.

PMID- 22664984
TI  - A mechanistic overview of translation initiation in eukaryotes.
AB  - Translation initiation in eukaryotes is a complex and highly regulated process
      requiring the action of at least 12 protein factors. The pathway is distinguished
      by the formation of a pre-initiation complex that recruits the 5' end of the mRNA
      and scans along it to locate the start codon. During the past decade, a
      combination of genetics, biochemistry and structural studies has begun to
      illuminate key molecular events in this critical phase of gene expression. Here,
      we outline our current understanding of eukaryotic translation initiation and
      discuss important outstanding challenges.

PMID- 22664985
TI  - Translational control by changes in poly(A) tail length: recycling mRNAs.
AB  - Beyond the well-known function of poly(A) tail length in mRNA stability, recent
      years have witnessed an explosion of information about how changes in tail length
      and the selection of alternative polyadenylation sites contribute to the
      translational regulation of a large portion of the genome. The mechanisms and
      factors mediating nuclear and cytoplasmic changes in poly(A) tail length have
      been studied in great detail, the targets of these mechanisms have been
      identified--in some cases by genome-wide screenings--and changes in poly(A) tail
      length are now implicated in a number of physiological and pathological
      processes. However, in very few cases have all three levels--mechanisms, targets
      and functions--been studied together.

PMID- 22664986
TI  - The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC.
AB  - Since their discovery almost two decades ago, microRNAs (miRNAs) have been shown
      to function by post-transcriptionally regulating protein accumulation.
      Understanding how miRNAs silence targeted mRNAs has been the focus of intensive
      research. Multiple models have been proposed, with few mechanistic details having
      been worked out. However, the past few years have witnessed a quantum leap
      forward in our understanding of the molecular mechanics of miRNA-mediated gene
      silencing. In this review we describe recent discoveries, with an emphasis on how
      miRISC post-transcriptionally controls gene expression by inhibiting translation
      and/or initiating mRNA decay, and how trans-acting factors control miRNA action.

PMID- 22664991
TI  - Role of vena cava inferior filter on neurosurgical deep venous thrombosis.
AB  - AIM: The patients who undergo neurosurgical procedures are at high risk for
      perioperative deep vein thrombosis and pulmonary embolism. Pharmacological
      prophylaxis with mechanic prophylaxis is a safe and effective way of preventing
      deep vein thrombosis and pulmonary thromboembolism in neurosurgery. However,
      pharmacological prophylaxis may increase the risk of hemorrhage after cranial or
      spinal operations. MATERIAL AND METHODS: Patients with vena cava inferior filter
      were retrospectively examined between 2003 and 2010. RESULTS: Approximately 1600
      patients per year are operated in our clinic. Deep vein thrombosis incidence is %
      1.2 - 2.3 in our department. Vena cava inferior filter is used on 13 patients who
      operated for various diagnoses, during the 2003 - 2010 period. None of these
      patients had new pulmonary thromboembolism after inserting vena cava inferior
      filter but two of them died cause of initial respiratory distress. CONCLUSION: We
      think that vena cava inferior filter in is safe and effective method for
      pulmonary thromboembolism prophylaxis, especially for patients with high bleeding
      risk and who cannot be anticoagulated. Further prospective studies with larger
      series are needed for evaluating long term complications and benefits.

PMID- 22664987
TI  - Translation drives mRNA quality control.
AB  - There are three predominant forms of co-translational mRNA surveillance: nonsense
      mediated decay (NMD), no-go decay (NGD) and nonstop decay (NSD). Although
      discussion of these pathways often focuses on mRNA fate, there is growing
      consensus that there are other important outcomes of these processes that must be
      simultaneously considered. Here, we seek to highlight similarities between NMD,
      NGD and NSD and their probable origins on the ribosome during translation.

PMID- 22664992
TI  - Cerebellar tonsillectomy with suboccipital decompression and duraplasty by small
      incision for Chiari I malformation (with syringomyelia): long term follow-up of
      76 surgically treated cases.
AB  - AIM: To explore the surgical effect of cerebellar tonsillectomy with suboccipital
      decompression and duraplasty by small surgical incision (3~4cm around the
      foramina magnum) on treating Chiari I Malformation (CM I) patients. MATERIAL AND
      METHODS: A retrospective study was undertaken on 76 CM I patients treated by this
      surgery. The surgical efficacy on clinical symptoms and syringomyelia were
      overall evaluated and analyzed. RESULTS: The study included 76 cases (36 men and
      40 women; age range, 5-58 years; mean age at surgery, 38.8 years). Preoperative
      MRI confirmed 56 cases associated with syringomyelia. The follow-up period ranged
      from 25 to 58 months (median, 46 months). At the end of follow-up, 61 patients
      (80.26%) had improved, 12 patients (15.79%) were stabilized, and 3 patients
      (3.95%) had worsened. In MRI scan, syrinx of 55 patients (98.21%) had improved or
      stabilized compare with syrinx growth in only one patient (1.79%). Statistical
      analysis reveal the surgical effect tend to be much better in patients with short
      duration of preoperative symptoms (P=0.001). CONCLUSION: Cerebellar tonsillectomy
      with suboccipital decompression and duraplasty can provide long-time cure for
      most CM I cases. Early diagnosis and surgery is necessary to improve the surgical
      effect. A 3~4cm incision around foramen magnum is enough for these operations and
      may be conducive to reduce postoperative complications.

PMID- 22664993
TI  - Use of topical landmarks for percutaneous projection of intracranial tumors for
      neurosurgical oncology.
AB  - AIM: The objective of this study was to introduce a surgical navigation method
      which provides a safe, quick and effective access to cortical and subcortical
      tumors, along with a review of other methods in use for this purpose. MATERIAL
      AND METHODS: 53 patients have been operated using this technique. The area
      overlying the tumor is shaved and one half of a smoothly cut hazelnut is taped on
      the skin. The precise localization of the hazelnut is confirmed with MRI and then
      stained. After general anesthesia, the stained impression is projected firstly to
      the bone, dura and then cortex respectively by the Midas Rex cutting tip.
      Cortical landmarks surrounding the tumor's cortical projection are further
      confirmed with ultrasonography. RESULTS: After removal, cortical and subcortical
      tumors were separately graded for efficiency. Grade 1 and 2 were accepted as
      precise access. Our method accordingly yielded 95.2% and 90.6% success rates for
      cortical and subcortical tumors respectively. CONCLUSION: Considering the
      method's success rate along with its inexpensiveness and modest technical
      requirements, it is believed that this method can be of widespread use.

PMID- 22664994
TI  - Neurosurgical training programme in selected European countries: from the young
      neurosurgeons' point of view.
AB  - AIM: In this paper we discuss the Neurosurgical Training Programme (NTP) in some
      European countries. MATERIAL AND METHODS: Although there is no official data on
      how many neurosurgeons are certified in Europe, our calculation shows that this
      number is somewhat lower than in the United States of America and even 3 times
      lower than in Japan (per 100.000 population). It is also evident that there is no
      consensus in the Programme duration or in the official NTP content, despite the
      recommendations of the EANS (The European Association of Neurosurgical
      Societies). Trainees from outside the European Union (EU) are under-represented
      in the EANS training courses. We believe that in the eastern part of Europe there
      is the most space for improvement in neurosurgical training. Solving of all these
      problems requires first and foremost their recognition and consideration - then
      devising a solution. CONCLUSION: The purpose of this paper is to compare and
      contrast several NTP's in Europe in order to promote a more coherent medical
      education. Some remarks and suggestions from the perspective of young
      neurosurgeons are given.

PMID- 22664995
TI  - Keyhole endoscopic hematoma evacuation in patients.
AB  - AIM: Keyhole endoscopy is a promising therapeutic option for spontaneous
      intracerebral hemorrhage (ICH). We sought to compare the clinical outcomes
      between keyhole endoscopy surgery and craniotomy for basal ganglia ICH. MATERIAL
      AND METHODS: The authors performed a retrospective analysis of the clinical and
      radiographic data obtained in 28 keyhole endoscopic procedures and 30 craniotomy
      procedures. Hematoma evacuation rate, infection rate, rebleeding and mean
      operation time were recorded as primary end points. Outcome Scale (GOS) values
      were recorded at the 3-month postoperative follow-up. The operation time from
      symptom onset is also studied between < 8 hours group and 8-24 hours group.
      RESULTS: The evacuation rate was significantly higher in the endoscopy group
      compared with the craniotomy group (P < 0.05), and infectious rate was lower in
      the endoscopy group compared with the craniotomy group( P < 0.05). Mortality
      rates between the 2 groups did not show statistically significant differences.
      The patients operated within 8h had better outcome (GOS 4 and 5) than that
      operated between 8-24h (p < 0.05). CONCLUSION: The data indicate that in patients
      with ICH, keyhole endoscopic surgery is safe and feasible, while operation within
      8h can promote recovery of patients. These preliminary results warrant further
      study in a large, prospective, randomized trial in the near future.

PMID- 22664996
TI  - Relationship of antioxidant enzyme activities with myelomeningocele.
AB  - AIM: To investigate the role of erythrocyte free radical scavenging enzyme
      activities (FRSE), carbonic anhydrase (CA) activity and malondialdehyde (MDA) in
      infants with myelomeningocele (MM). MATERIAL AND METHODS: We compared antioxidant
      enzyme activities and MDA level in 40 individuals (10 infants with MM, 10 healthy
      infants; and mothers of these two groups) with age-matched subjects. Erythrocyte
      FRSE included catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase
      (GPX) and glutathione-S- transferase (GST). RESULTS: CA, CAT, SOD, GPX and GST
      concentrations were lower in all of the infants with MM compared to healthy
      infants. The mothers of infants with MM also had lower CA, CAT, SOD, GPX and GST
      activities than healthy mothers. It was also found out that the MDA level as a
      marker of oxidative damage was higher in infants with MM and their mothers than
      in healthy infants and their mothers. CONCLUSION: Lower FRSE activities indicate
      an increased frequency of MM. Free radicals (FRs) such as MDA may play a
      significant role in the etiology of MM.

PMID- 22664997
TI  - Traumatic peritentorial subdural hematomas: a study of 32 cases.
AB  - AIM: This study aimed to investigate the clinicoradiological features in patients
      with traumatic peritentorial subdural hematomas (SDHs). MATERIAL AND METHODS: We
      retrospectively reviewed the clinical and radiological findings, management
      criteria, and outcomes in 32 patients with peritentorial SDHs. The outcomes were
      classified as favorable (good recovery or moderate disability) or poor (severe
      disability, vegetative state, or death). RESULTS: Of the 32 patients, 19 were
      male and 13 were female. The patients' ages ranged from 10-92 years (mean age,
      60.9 years). Coagulopathies were observed in 23 patients. Twenty-four patients
      presented with associated intracranial lesions. Eighteen patients had favorable
      outcomes and 14 had poor outcomes. All patients were treated conservatively. The
      presence of coagulopathy (p = 0.024) and presence of convexity SDH (p = 0.008)
      correlated with the outcome. CONCLUSION: The patients with traumatic
      peritentorial SDHs were predominantly male and relatively elderly, and had a high
      incidence of coagulopathy, associated intracranial lesions (especially falx
      SDHs), a high rate of impact in the occipital or frontal regions, and a low
      incidence of skull fractures. The factors that were correlated with outcome in
      patients receiving conservative therapy were the presence of coagulopathy and the
      presence of convexity SDH.

PMID- 22664998
TI  - Comparative assessment of neuro-cognitive impairments among patients with brain
      tumor and healthy adults.
AB  - AIM: Most brain tumor patients encounter cognitive impairments. Coping with such
      challenges is intolerable for them. OBJECTIVE: This study tries to determine the
      diagnostic role of cognitive tests, CPT, Stroop and TOL, in assessing neuro
      cognitive impairments among patients with brain tumor and healthy participants.
      MATERIAL AND METHODS: A cross-sectional study was done on a sample of 15 to 65
      years old of 84 brain tumor patients and 84 healthy Iranians. Participants of
      both groups were physically and mentally examined and approved by neurosurgeons,
      neurologists and psychiatrists. By completing the questionnaires, they all
      entered the study and were referred to the neuroscientist for performing the
      tests. RESULTS: According to CPT, Stroop and TOL tests, the performance of both
      groups was significantly regarding about age, sex and education variables (P <
      0.05). CONCLUSION: Brain tumor patients in comparison to healthy participants met
      more cognitive changes on sustained, selective attention and planning. Therefore,
      diagnosis and assessment of these cognitive changes before and after the surgery
      can help rehabilitating patients' brains and improve their lives quality.

PMID- 22664999
TI  - Anatomy of Meckel's cave and the trigeminal ganglion: anatomical landmarks for a
      safer approach to them.
AB  - AIM: Surgical approaches to Meckel's cave (MC) are often technically difficult
      and sometimes associated with postoperative morbidity. The relationship of
      surgical landmarks to relevant anatomy is important. Therefore, we attempted to
      delineate quantitatively their anatomy and the relationships between MC and
      surrounding structures. MATERIAL AND METHODS: With the aid of a surgical
      microscope, MC and its contents were studied in 15 formalin-fixed cadaver head
      specimens. Measurements were made and their relationships were observed. RESULTS:
      The distance from the zygomatic arch and the lateral end of the petrous ridge to
      MC was 26.5 and 34.4 mm, respectively. The distance from the arcuate eminence,
      the facial nerve hiatus, and the foramen spinosum to MC was 16.6, 12.8 and 7.46
      mm respectively. The TG lay 5.81 mm posterior to the foramen ovale. The distance
      from the abducens, trochlear and oculomotor nerves to the trigeminal ganglion was
      1.87, 5.53 and 6.57 mm respectively. The distance from the posterior and the
      anterior walls of the sigmoid sinus to the trigeminal porus was 43.6 and 33.1 mm
      respectively. The trigeminal porus was on average 7.19 mm from the anterior wall
      of the internal acoustic meatus. CONCLUSION: The anatomical landmarks as
      presented herein regarding MC may be used for a safer skull base approach to the
      region.

PMID- 22665000
TI  - Does TLIF aggravate adjacent segmental degeneration more adversely than ALIF? A
      finite element study.
AB  - AIM: To determine whether transforaminal lumbar interbody fusion aggravate
      adjacent segmental degeneration more adversely than anterior lumbar interbody
      fusion. MATERIAL AND METHODS: A normal finite element model, an anterior lumbar
      interbody fusion model and a transforaminal lumbar interbody fusion model of L3-5
      were developed. 800 N compressive loading plus 10 Nm moments simulating flexion,
      extension, lateral bending and axial rotation were imposed on L3 superior
      endplate. The intradiscal pressure, intersegmental rotation and tresca stress in
      L3-4 were investigated. RESULTS: Under all loading directions, the values of
      three parameters in transforaminal lumbar interbody fusion model were the highest
      and those in normal model were the lowest, and the values in the ALIF model were
      higher than the normal model while lower than the TLIF model. In the ALIF and
      normal models, the values of the three parameters on left lateral bending and
      axial rotation were equal to those on right lateral bending and axial rotation.
      However, in the TILF model, the values on right lateral bending and axial
      rotation were larger than those on left lateral bending and axial rotation.
      CONCLUSION: Transforaminal lumbar interbody fusion aggravates adjacent segmental
      degeneration more adversely than anterior lumbar interbody fusion.

PMID- 22665001
TI  - Surgical strategies for neurological function preservation in severe brain
      contusion.
AB  - AIM: Traditional surgical strategies for severe brain contusion are constantly
      associated with variable degree of postoperative neurological dysfunction, which
      is in part attributed to the location and severity of contusion. The purpose of
      this study was to compare and evaluate these current surgical strategies, with an
      emphasis on neurological function preservation. MATERIAL AND METHODS: A
      retrospective review of surgical strategies employed for 142 cases of severe
      brain contusion was performed. The surgical strategies were stratified into four
      types, Type I, Simple DC, without resection of contusion; II, Resection of
      contusion, combined with DC; III, Safe cerebral lobe resection and DC, without
      resection of contusion; IV, Simple resection of contusion, without decompression.
      The patients were accordingly separated into four groups. RESULTS: The favorable
      prognosis rate in Group I, II and III was higher than Group IV on 6-month follow
      up Glasgow Outcome Score (GOS). No significant difference of mortality rate was
      observed among Group I, II and III (p > 0.05), but the favorable prognosis rate
      of Group II was lower than Group I and III (p < 0.05). CONCLUSION: Simple DC and
      safe cerebral lobe resection combined with DC might achieve better therapeutic
      effect, and could be recommended as the preferred surgical strategies for severe
      brain contusion.

PMID- 22665002
TI  - A new technique for clipping diaphragm defects in transsphenoidal surgery.
AB  - AIM: To deal with postoperative CSF rhinorrhea, we developed a new technique
      using titanium/aneurysm clips to envelope the diaphragm defect to avoid
      postoperative CSF rhinorrhea. MATERIAL AND METHODS: From January 2007 through
      December 2010, we used a new technique of clipping diaphragm defects to prevent
      CSF rhinorrhea in 57 of 510 patients (group 1) who underwent transsphenoidal
      surgery. The incidence of postoperative CSF rhinorrhea was compared with that of
      245 patients who underwent transsphenoidal surgery before the usage of this
      clipping technique between January 2004 and December 2006 (group 2). RESULTS:
      Postoperative CSF rhinorrhea developed in 8 (1.57%) patients of the 510 patients
      in group 1 while the new technique was used, while 17 (6.94%) patients of the 245
      patients in group 2 developed CSF rhinorrhea before the usage of this technique
      (chi2 =14.907, P < .001). No device-related complication such as optical chiasm
      herniation after clipping the diaphragm defect was observed. CONCLUSION: Clipping
      the diaphragm defect with the titanium/aneurysm clips is effective and
      practicable to prevent postoperative CSF rhinorrhea, it can also avoid
      unnecessary autologous tissue grafting and postoperative lumbar drainage.

PMID- 22665003
TI  - Evaluation of cerebral arteriovenous malformations using image fusion combining
      three-dimensional digital subtraction angiography with magnetic resonance
      imaging.
AB  - AIM: An image fusion of 3-dimensional (D) digital subtraction angiography (DSA)
      and magnetic resonance (MR) images, DSA-MR fusion, can simultaneously visualize
      both information of the vasculature provided by 3D DSA and of the soft tissues
      provided by MR images. The authors assessed the usefulness of DSA-MR fusion
      images concerning the pretreatment evaluation for cerebral arteriovenous
      malformation (AVM). MATERIAL AND METHODS: Seven consecutive patients underwent
      pretreatment DSA-MR fusion and then microsurgical, endovascular and/ or
      radiosurgical treatments. RESULTS: DSA-MR fusion images clearly showed the
      spatial relationship among AVM, its feeding artery, draining vein, surrounding
      artery feeding the normal brain tissue, hematoma and brain tissues (gyri or brain
      surface) with reasonable post-processing time. CONCLUSION: These findings were
      useful for treatment planning for AVM, especially to enable neurosurgeons to
      easily understand the surgical anatomy preoperatively.

PMID- 22665004
TI  - The association of sphenoidal encephalocele and right anophthalmia with septo
      optic dysplasia: a case report.
AB  - Septo-optic dysplasia (SOD) is an extremely rare congenital anomaly,    
      characterized with optic nerve hypoplasia and absence of septum pellucidum    
      and/or pituitary dysfunction. In addition to classical findings of SOD, we    
      report for the first time an 11-year-old boy, with encephalocele extending to    
      the right sphenoidal sinus, right anophthalmia and normal pituitary functions.   
      Despite all the major anomalies, the patient's presenting symptoms were very few
      and during the 11-year period the SDO had caused no complaints in our case.  
      These findings show that the SOD course may be fairly benign. No neurological  
      problem was encountered in the patient's follow-up, except headache. We believe
      that SOD should be kept in mind because of its rarity and the severity of its
      combined pathologies.

PMID- 22665005
TI  - Simultaneous cranial subarachnoid hemorrhage and spinal subdural hematoma.
AB  - We report a rare case of simultaneous cranial subarachnoid and spinal subdural   
      hematoma (SDH) in a 42-year-old man who was on Warfarin therapy after    
      cardiac bypass surgery. Computed tomography at presentation revealed a cranial   
      subarachnoid hemorrhage, and spinal Magnetic Resonance Imaging (MRI) showed a   
      spinal SDH extending from the T6 to L5 segments. He had paraparesis due to    
      spinal cord compression. The patient was managed conservatively due to his poor  
      general condition and was infused with intravenous steroid therapy, but he    
      experienced sudden cardiac arrest 5 hours later after being admitted to the    
      hospital. This case is of interest because of its first presentation of spinal   
      subdural hematoma and cranial subarachnoid hemorrhage simultaneously and it is  
      also the second longest vertebral segmental spread in the literature.

PMID- 22665006
TI  - Cauda equina paraganglioma with ependymoma-like histology: a case report.
AB  - Paraganglioma affecting the cauda equina region is very rare and can be    
      misinterpreted as an ependymoma which is more common at this site. A 38-year-old 
      woman with a paraganglioma in the cauda equina is presented. MRI revealed a   
      well-circumscribed, intradural, extramedullary tumor nodule with the dimensions 
      of 2.5x1x1 cm. The patient underwent L3 laminectomy and total excision of the 
      tumor. The tumor was diagnosed as ependymoma and the patient was decided to   
      undergo adjuvant radiotherapy. The patient applied to our medical center for a  
      second opinion. Histopathologically, her tumor was found to be a paraganglioma 
      with ependymal features. Therefore no adjuvant therapy was applied. There is
      no     evidence of recurrence or metastases for 15 months after her operation.   
      Paraganglioma in the cauda equina/ filum terminale is very rare and can be    
      misdiagnosed as ependymoma especially when it exhibits ependymoma-like    
      histology. This rare form of paraganglioma behaves like a WHO grade I tumor of   
      CNS like classic paraganglioma. No recurrence or metastasis is expected when it 
      is totally resected. Morphology can be misleading hence immunohistochemistry  
      and/or ultrastructural study is necessary for correct diagnosis.

PMID- 22665007
TI  - Urinary incontinence triggered by stretching exercises.
AB  - A 47-year-old female patient who experienced urinary urgency after having    
      stretching exercises of her legs is presented. Stretching of the legs are    
      thought to be responsible for conus medullaris tethering which in turn causes    
      urinary complaints. What is interesting in this case is that her complaints    
      about urinary urgency stopped as she quit stretching exercise movements of her   
      legs. There are some examples of such cases in the literature. The urinary    
      urgency after stretching exercises warned us to investigate this patient in    
      regard to tethered conus medullaris. Tethering of the conus medullaris can be    
      temporary and can cause reversible functional disorders of the bladder.    
      Incontinence at any age should be evaluated cautiously as it could be a sign of  
      an underlying important developmental failure.

PMID- 22665008
TI  - A craniocervical teratoma with an encephalocele-like appearance.
AB  - Teratomas are rare congenital tumors. Teratomas frequently occur in adult    
      ovaries, but can be located primarily in the sacrococcygeal zone and    
      intracranial compartment in newborns. Teratomas are rare in the head and neck    
      region. Teratomas arise following a sequence of cells derived from more than one 
      germ layer at different regions of the body due to a change in location of
      germ     cells, and contain ectodermic, endodermic, and mesodermic tissues.
      Herein we     detail the follow-up and treatment of a newborn with a mass that
      was located at     the back of the head and was referred to our Neurosurgery
      Clinic with a     pathologic diagnosis of a grade II-III immature teratoma
      resembling an     encephalocele.

PMID- 22665009
TI  - Thoracic meningioma masquerading as chronic abdominal pain.
AB  - Chronic abdominal pain without a structural or metabolic gastroenterological    
      etiology can be extremely challenging to diagnose. Patients presenting with an   
      associated radicular pattern of pain may alert the clinician to a possible    
      structural neurological cause of the symptoms. We present the case of a     70
      year-old woman who presented to our institution with an 18-month history of    
      right upper quadrant abdominal pain. She had no associated symptoms or provoking 
      factors. She underwent an extensive gastroenterology evaluation, including    
      colonoscopy that was unrevealing. Ultrasound demonstrated gallstones and she was 
      evaluated for cholecystectomy. She subsequently developed right costal margin 
      pain. Her symptoms remained stable over the course of the next year. Follow-up
      general surgical evaluation was still unconvincing that the gallstones were
      the     etiology of her symptoms. A thoracic spinal MR demonstrated a large
      intradural     extramedullary mass at T8. The patient's neurological exam was
      normal. She     underwent a thoracic laminectomy and resection of meningioma with
      intraoperative     electrophysiological monitoring. Her abdominal pain resolved.
      Patients can     present with months to years of elusive abdominal symptoms only
      to be eventually     found to be harboring an undiagnosed spinal tumor. We
      discuss the case and     review the literature reports of spinal tumors
      masquerading as chronic abdominal     pain.

PMID- 22665010
TI  - Acute interdural hematoma mimicking epidural hematoma: a case report.
AB  - Intracranial hematoma rarely presents between two dural layers of pachimeninges. 
      Here, we present a case of an interdural hematoma with similar appearance to
      an     epidural hematoma. A 51-year-old man presented with a left temporal
      contusion     following a motor vehicle accident. After craniotomy and contusion
      removal, the     post-operative CT scan showed a parietal intracranial hematoma
      located posterior     and superior to the bone flap. The CT scan appearance of
      the new hematoma was     similar to the CT scan appearance of an epidural
      hematoma. Upon operation, we     determined that the hematoma was located between
      two layers of dura mater, i.e.,     an interdural hematoma. We removed the
      hematoma and sutured the two layers of     dura to each other at multiple sites.
      Interdural hematoma is a rare entity. Its     appearance in a CT scan can be
      mistaken for an extradural hematoma.

PMID- 22665011
TI  - Carotid agenesis with intercavernous anastomosis.
AB  - Agenesis of internal carotid artery (ICA) is rare. Association of agenesis with  
      abnormal arterial communication between the cavernous segment of the carotid   
      arteries is extremely rare. We present a case of a middle-aged woman who    
      presented with sudden onset severe holocranial headache. She was investigated    
      and diagnosed to have sub-arachnoid hemorrhage on CT scan. Digital Subtraction   
      Angiogram revealed absent right internal carotid artery. The right middle    
      cerebral artery received blood supply from an incidentally detected    
      intercavernous anastomosis from the left internal carotid artery. No aneurysm,   
      arteriovenous malformation or any other vascular abnormality was detected. The  
      patient was managed conservatively. She has been asymptomatic for five years on
      follow up.

PMID- 22665012
TI  - Brain abscess caused by Gemella morbillorum: case report and review of the
      literature.
AB  - We describe a rare case of cerebral abscess in an immunocompetent 67-year-old    
      male with Gemella morbillorum as the causative agent. Gemella morbillorum is an  
      aerobic gram positive coccus and is deemed to be a normal inhabitant of the
      oral     cavity. The aim of this report is to introduce Gemella morbillorum as
      the     emerging pathogen involved in brain abscesses. To the best of our
      knowledge only     eight cases of Gemella morbillorum brain abscess have been
      reported in the     literature. An exhaustive review of the literature is
      included with emphasis on     the primary source of infection, clinical
      presentation, radiological diagnosis,     and treatment modalities.

PMID- 22665013
TI  - A case of glioblastoma multiforme with long term survival: can we predict the
      outcome?
AB  - Glioblastoma Multiforme (GBM) presents a major challenge for a neurosurgeon as   
      the most common primary malignant tumour of the central nervous system. The    
      median life span after the diagnosis still remains between 6 months to 1 year    
      even after gross total excision of the tumour. However, few patients survive    
      long and develop recurrence after a substantial time interval. The exact reason  
      behind the long term survival in GBM cases remains obscure. However, few    
      predictors have been identified of late. Young age, p53 positivity,     O6
      methylguanine methyltransferase (MGMT) methylation, aggressive surgical    
      resection and a good pre-operative Karnofsky Performance Score (KPS) have been   
      identified with good survival rates in these select cases. Immunohistochemistry 
      forms an integral part of a glioblastoma work up and it must be done in each
      and     every case as it may provide crucial insights regarding prognosis. We
      report a     rare case of glioblastoma multiforme with a long term survival of 20
      years. This     patient developed a frontal cystic tumour bilaterally in these 20
      years and is     still leading an active life. The clinical summary, imaging,
      histopathology,     immunohistochemistry along with relevant literature have been
      discussed.

PMID- 22665014
TI  - Cerebellar low-grade oligoastrocytoma presenting with subarachnoid haemorrhage.
AB  - Subarachnoid haemorrhage (SAH) associated with intra-axial tumours is extremely  
      uncommon and is usually seen in association with intratumoural bleed. Tumours  
      located near the ventricle or subarachnoid spaces have a higher propensity for 
      SAH compared to intraparenchymal lesions. Low-grade tumours rarely demonstrate
      any evidence of bleed on imaging. Oligoastrocytomas of the posterior fossa
      are     rare tumours in adults and their presentation with intratumoural
      haemorrhage and     SAH is unknown. We report a unique case of cerebellar low
      grade oligoastrocytoma     that mimicked a tentorial-based extraaxial lesion on
      imaging and presented with     SAH. Susceptibility-weighted magnetic resonance
      imaging is a useful imaging     modality to demonstrate blood within and outside
      the tumour.

PMID- 22665015
TI  - Solitary lumbar osteochondroma presenting with foot-drop: a case report.
AB  - Although osteochondroma is the most common benign bone tumor, the lumbar spine   
      is anuncommon localization for solitary osteochondroma. Solitary lumbar    
      osteochondromas rarely affect the neurological structures, because most of the   
      lesions grow out of the spinal canal. We report a 48-year-old patient suffering 
      from right foot-drop due to acute compression of right L4 nerve root by a
      lesion     expanding into the spinal canal, originating from the right inferior
      articular     facet of the third lumbar vertebrae. The symptoms improved after
      surgical     removal of the lesion and histopathological examination of the
      lesion confirmed     the diagnosis of osteochondroma. To the best of our
      knowledge, this is a unique     case report in the literature.

PMID- 22665016
TI  - Primary osteoma of the orbit with atypical facial pain: case report and
      literature review.
AB  - Osteoma is a benign, slowly growing tumor that mainly occurs in the bones and
      cavities of the middle third of the face, representing the most frequent benign
      tumor of the paranasal sinuses. It rarely originates primarily from the orbit.
      Most of these lesions develop in the fourth to fifth decades of life, and are
      more commonly encountered in males. In the English literature, there are so far
      three reported cases of primary osteoma of the orbit that originated from the
      sphenoid bone. Here we present another case of a primary osteoma of the orbit
      presenting with atypical facial pain and discuss the relevant literature.

PMID- 22665017
TI  - A retained wood penetrating the superior orbital fissure in a neurologically
      intact child.
AB  - Transorbital intracranial injuries due to a wooden foreign body traversing
      superior orbital fissure is an extremely rare condition. A 9-year-old boy was
      struck by a tree branch in the left eye while playing in the garden two months
      ago. On physical examination, the patient had only a hypertrophic scar on his
      medial side of left upper eyelid at the admission. A history of recurrent
      cutaneous fistula from the puncture site due to a retained foreign body was
      suspected, and the patient was hospitalized to evaluate and remove the object to
      prevent severe infection. Afterwards, the child was operated successfully via the
      left transcranial route to detect and remove the foreign body. The authors
      described an unusual case of wooden foreign body that traversed the superior
      orbital fissure yet caused no deficit and was associated with no fracture. Even
      if symptoms are absent, removal of a wooden foreign body should be immediately
      performed to prevent sight-threatening and life-threatening complications.

PMID- 22665018
TI  - The effects of analgesia-sedation on the immune system before and after cerebral
      digital subtraction angiography.

PMID- 22665019
TI  - Plasma protein adsorption to zwitterionic poly (carboxybetaine methacrylate)
      modified surfaces: chain chemistry and end-group effects on protein adsorption
      kinetics, adsorbed amounts and immunoblots.
AB  - Protein-surface interactions are crucial to the overall biocompatability of
      biomaterials, and are thought to be the impetus towards the adverse host
      responses such as blood coagulation and complement activation. Only a few studies
      hint at the ultra-low fouling potential of zwitterionic poly(carboxybetaine
      methacrylate) (PCBMA) grafted surfaces and, of those, very few systematically
      investigate their non-fouling behavior. In this work, single protein adsorption
      studies as well as protein adsorption from complex solutions (i.e. human plasma)
      were used to evaluate the non-fouling potential of PCBMA grafted silica wafers
      prepared by nitroxide-mediated free radical polymerization. PCBMAs used for
      surface grafting varied in charge separating spacer groups that influence the
      overall surface charges, and chain end-groups that influence the overall
      hydrophilicity, thereby, allows a better understanding of these effects towards
      the protein adsorption for these materials. In situ ellipsometry was used to
      quantify the adsorbed layer thickness and adsorption kinetics for the adsorption
      of four proteins from single protein buffer solutions, viz, lysozyme, alpha
      lactalbumin, human serum albumin and fibrinogen. Total amount of protein adsorbed
      on surfaces differed as a function of surface properties and protein
      characteristics. Finally, immunoblots results showed that human plasma protein
      adsorption to these surfaces resulted, primarily, in the adsorption of human
      serum albumin, with total protein adsorbed amounts being the lowest for PCBMA-3
      (TEMPO). It was apparent that surface charge and chain hydrophilicity directly
      influenced protein adsorption behavior of PCBMA systems and are promising
      materials for biomedical applications.

PMID- 22665020
TI  - Unique antineoplastic profile of Saquinavir-NO, a novel NO-derivative of the
      protease inhibitor Saquinavir, on the in vitro and in vivo tumor formation of
      A375 human melanoma cells.
AB  - We have recently shown that covalent attachment of the nitric oxide (NO) moiety
      to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new
      chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer
      properties and reduced toxicity both in vitro and in vivo. The aim of this study
      was to address several unanswered questions both on the pharmacological profile
      of Saq-NO as well as on the in vivo role of NO in the oncogenesis of A375 human
      melanoma cells. To this end, we have evaluated here the impact of single and
      combined effects of Saq-NO, Saq, the NO-donor DETA NONOate and the iNOS inhibitor
      L-NAME on the in vitro as well as in vivo growth of the iNOS positive A375 cells.
      Our data confirm clear-cut evidence for a strong and powerful anti-melanoma
      action of Saq-NO that is not duplicable by the combined use of Saq and DETA
      NONOate. Surprisingly, but also in agreement with the complex and multifaceted
      role of endogenous NO in A375 cells, both DETA NONOate and L-NAME significantly
      suppressed the in vivo growth of xenotransplants.

PMID- 22665021
TI  - Refractory periods in SUNCT.

PMID- 22665022
TI  - Rate vs rhythm control in atrial fibrillation: can observational data trump
      randomized trial results?

PMID- 22665026
TI  - Handy-dads to the rescue.

PMID- 22665027
TI  - The American Pediatric Society commentary: the future of pediatric physician
      scientists is in our hands.

PMID- 22665029
TI  - Prospective associations between physical activity and obesity among adolescent
      girls: racial differences and implications for prevention.
AB  - OBJECTIVE: To test for differences in prospective associations between physical
      activity and obesity among black and white adolescent girls. DESIGN: Prospective
      cohort study using data from the National Heart, Lung, and Blood Institute Growth
      and Health Study. SETTING Multicenter study at the University of California
      (Berkeley), Children's Medical Center at the University of Cincinnati
      (Cincinnati, Ohio), and Westat, Inc, and Group Health Association (Rockville,
      Maryland). PARTICIPANTS: A total of 1148 adolescent girls (538 black and 610
      white) who provided valid data on levels of physical activity and obesity at ages
      12 and 14 years. INTERVENTION: Physical activity, assessed as accelerometer
      counts per day. MAIN OUTCOME MEASURES: Three measurements of obesity were
      obtained using the Centers for Disease Control and Prevention definition of
      obesity (at or above the age-specific 95th percentile of body mass index), the
      International Obesity Task Force reference body mass index cut points for obesity
      in children, and the sums of skinfold thickness (with the cohort >=90th
      percentile as indicative of obesity). RESULTS: We found a strong negative dose
      response association between quartiles of accelerometer counts per day at age 12
      years and obesity at age 14 years (using all 3 measurements of obesity) in white
      but not black girls (P < .001 for body mass index interaction and P = .06 for
      sums of skinfold thickness interaction). The odds ratios for obesity (using the
      cohort >=90th percentile for sums of skinfold thickness) in adjusted models
      between the top and the bottom quartiles of accelerometer counts per day were
      0.15 (95% CI, 0.04-0.63; P = .03 for trend) in white girls and 0.85 (95% CI, 0.32
      2.26; P = .93 for trend) in black girls. CONCLUSIONS: Higher levels of physical
      activity are prospectively associated with lower levels of obesity in white
      adolescent girls but not in black adolescent girls. Obesity prevention
      interventions may need to be adapted to account for the finding that black girls
      are less sensitive to the effects of physical activity.

PMID- 22665028
TI  - Polygenic risk, rapid childhood growth, and the development of obesity: evidence
      from a 4-decade longitudinal study.
AB  - OBJECTIVE: To test how genomic loci identified in genome-wide association studies
      influence the development of obesity. DESIGN: A 38-year prospective longitudinal
      study of a representative birth cohort. SETTING: The Dunedin Multidisciplinary
      Health and Development Study, Dunedin, New Zealand. PARTICIPANTS: One thousand
      thirty-seven male and female study members. MAIN EXPOSURES: We assessed genetic
      risk with a multilocus genetic risk score. The genetic risk score was composed of
      single-nucleotide polymorphisms identified in genome-wide association studies of
      obesity-related phenotypes. We assessed family history from parent body mass
      index data collected when study members were 11 years of age. MAIN OUTCOME
      MEASURES: Body mass index growth curves, developmental phenotypes of obesity, and
      adult obesity outcomes were defined from anthropometric assessments at birth and
      at 12 subsequent in-person interviews through 38 years of age. RESULTS:
      Individuals with higher genetic risk scores were more likely to be chronically
      obese in adulthood. Genetic risk first manifested as rapid growth during early
      childhood. Genetic risk was unrelated to birth weight. After birth, children at
      higher genetic risk gained weight more rapidly and reached adiposity rebound
      earlier and at a higher body mass index. In turn, these developmental phenotypes
      predicted adult obesity, mediating about half the genetic effect on adult obesity
      risk. Genetic associations with growth and obesity risk were independent of
      family history, indicating that the genetic risk score could provide novel
      information to clinicians. CONCLUSIONS: Genetic variation linked with obesity
      risk operates, in part, through accelerating growth in the early childhood years
      after birth. Etiological research and prevention strategies should target early
      childhood to address the obesity epidemic.

PMID- 22665031
TI  - Gestational ageism.
AB  - Published guidelines for resuscitation of extremely premature infants emphasize
      the importance of the gestational age of the infant. However, some ethicists and
      pediatricians have questioned these guidelines, suggesting that this may
      represent a form of discrimination. A policy of nonresuscitation of elderly
      patients older than a certain age would constitute a form of ageism and would
      likely be unacceptable to the broader community. Are resuscitation decisions for
      premature newborn infants analogous to resuscitation of elderly patients? Are
      current neonatal resuscitation guidelines discriminatory?  This article looks at
      the relationship between discrimination based on gestational age and
      chronological age. There are 2 levels of gestational ageism and 2 separate
      strands of argument against gestational age guidelines. I conclude that
      resuscitation decisions for premature infants share many features with those for
      elderly patients, although there are also some relevant differences. I propose
      the use of gestational age equivalence as an alternative framework for practice.

PMID- 22665030
TI  - Staphylococcus aureus colonization in children with community-associated
      Staphylococcus aureus skin infections and their household contacts.
AB  - OBJECTIVES: To measure prevalence of Staphylococcus aureus colonization in
      household contacts of children with acute S aureus skin and soft tissue
      infections (SSTI), determine risk factors for S aureus colonization in household
      contacts, and assess anatomic sites of S aureus colonization in patients and
      household contacts. DESIGN: Cross-sectional study. SETTING: St Louis Children's
      Hospital Emergency Department and ambulatory wound center and 9 community
      pediatric practices affiliated with a practice-based research network.
      PARTICIPANTS: Patients with community-associated S aureus SSTI and S aureus
      colonization (in the nose, axilla, and/or inguinal folds) and their household
      contacts. OUTCOME MEASURES: Colonization of household contacts of pediatric
      patients with S aureus colonization and SSTI. RESULTS: Of 183 index patients, 112
      (61%) were colonized with methicillin-resistant S aureus (MRSA); 54 (30%), with
      methicillin-sensitive S aureus (MSSA); and 17 (9%), with both MRSA and MSSA. Of
      609 household contacts, 323 (53%) were colonized with S aureus: 115 (19%) with
      MRSA, 195 (32%) with MSSA, and 13 (2%) with both. Parents were more likely than
      other household contacts to be colonized with MRSA (odds ratio, 1.72; 95% CI,
      1.12 to 2.63). Methicillin-resistant S aureus colonized the inguinal folds more
      frequently than MSSA (odds ratio, 1.67; 95% CI, 1.16 to 2.41), and MSSA colonized
      the nose more frequently than MRSA (odds ratio, 1.75; 95% CI, 1.19 to 2.56).
      CONCLUSIONS: Household contacts of children with S aureus SSTI had a high rate of
      MRSA colonization compared with the general population. The inguinal fold is a
      prominent site of MRSA colonization, which may be an important consideration for
      active surveillance programs in hospitals.

PMID- 22665032
TI  - Picture of the month. Primary hypothyroidism.

PMID- 22665034
TI  - Translating developmental genetic findings into obesity-related clinical
      practice: are we there yet?

PMID- 22665036
TI  - Justifiable and unjustifiable ageism.

PMID- 22665035
TI  - Evaluating therapeutic hypothermia: parental perspectives should be explicitly
      represented in future research.

PMID- 22665037
TI  - Advice for patients. Staphylococcal infections.

PMID- 22665038
TI  - Cooperation of protease-activated receptor 1 and integrin alphanubeta5 in
      thrombin-mediated lung cancer cell invasion.
AB  - Protease-activated receptor 1 (PAR1) and integrins play an important role in
      thrombin-mediated tumor cell invasion. However, the role of PAR1 and integrin
      alphanubeta5 and the relationship between the two receptors in thrombin-induced
      lung cancer invasion remains unknown. Moreover, the mechanisms through which
      immobilized thrombin facilitates tumor invasion are poorly understood. In this
      study, both native and immobilized thrombin promoted lung cancer cell adhesion,
      migration and extracellular signal-regulated kinase phosphorylation. Integrin
      alphanubeta5 is involved in both native and immobilized thrombin-mediated tumor
      cell invasion; PAR1 had no effect on immobilized thrombin-mediated cell invasion.
      PAR1 and integrin alphanubeta5 colocalized on the surface of native thrombin
      treated cells. This study suggests that targeting of integrin alphanubeta5 or the
      PAR1-integrin alphanubeta5 complex may present an important therapeutic
      opportunity to prevent lung cancer invasion.

PMID- 22665039
TI  - REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic
      agent for bladder cancer.
AB  - Bladder cancer is one of the most common urogenital malignancies. The
      intravesical instillation of anticancer agents is an attractive strategy to treat
      a superficial lesion or floating/disseminated cancer cells after transurethral
      operation. An adenovirus carrying REIC/Dkk-3, a tumor suppressor gene (Ad-REIC),
      exhibits cancer-specific apoptotic effects in various types of cancer cells. The
      aim of the present study was to examine the potential of Ad-REIC as a therapeutic
      agent for bladder cancer. KK47 and RT4 human bladder cancer cells were sensitive
      to the Ad-REIC treatment for apoptosis induction, but some human bladder cancer
      cell lines (T24, J82 and TccSup) were resistant. Significant cell growth
      inhibition was observed when these resistant cancer cell lines were treated with
      Ad-REIC in a condition of floating cells, which is clinically observed after
      transurethral operation and becomes a cause of intravesical cancer dissemination.
      The therapeutic potential of Ad-REIC for the treatment of multidrug-resistant
      bladder cancer was investigated. The adriamycin-resistant KK47 bladder cancer
      cells (KK47/ADM), which also present multidrug resistance, showed induction of
      significant apoptosis following Ad-REIC treatment. The Ad-REIC treatment induced
      downregulation of P-glycoprotein in KK47/ADM cells and restored the sensitivity
      to doxorubicin (adriamycin). Ad-REIC suppressed P-glycoprotein expression in a c
      Jun-NH2-kinase (JNK)-dependent manner. Therefore, the current study indicated two
      therapeutic aspects of the Ad-REIC agent against human bladder cancer cells, as
      an apoptosis inducer/cell growth inhibitor and as a sensitizer of
      chemotherapeutic agents in multidrug-resistant cancer cells. The intravesical
      instillation of Ad-REIC could be an attractive therapeutic method in human
      bladder cancer where the treatment of superficial lesions and
      floating/disseminated or multidrug-resistant cancer cells is necessary.

PMID- 22665040
TI  - PKC signaling is involved in the regulation of progranulin (acrogranin/PC-cell
      derived growth factor/granulin-epithelin precursor) protein expression in human
      ovarian cancer cell lines.
AB  - OBJECTIVE: Overexpression of progranulin (also named acrogranin, PC-cell-derived
      growth factor, or granulin-epithelin precursor) is associated with ovarian
      cancer, specifically with cell proliferation, malignancy, chemoresistance, and
      shortened overall survival. The objective of the current study is to identify the
      signaling pathways involved in the regulation of progranulin expression in
      ovarian cancer cell lines. METHODS: We studied the relation of protein kinase C
      (PKC), phosphatidylinositol 3-kinase, protein kinase A, P38, extracellular signal
      regulated kinase, and Akt pathways on the modulation of progranulin expression
      levels in NIH-OVCAR-3 and SK-OV-3 ovarian cancer cell lines. The different
      pathways were examined using pharmacological inhibitors (calphostin C, LY294002,
      H89, SB203580, PD98059, and Akt Inhibitor), and mRNA and protein progranulin
      expression were analyzed by reverse transcriptase polymerase chain reaction and
      Western blot techniques, respectively. RESULTS: Inhibition of PKC signal
      transduction pathway by calphostin C decreased in a dose-dependent manner protein
      but not mRNA levels of progranulin in both ovarian cancer cell lines. LY294002
      but not wortmannin, which are phosphatidylinositol 3-kinase inhibitors, also
      diminished the expression of progranulin in both cell lines. In addition,
      LY294002 treatment produced a significant reduction in cell viability. Inhibition
      of protein kinase A, P38, extracellular signal-regulated kinase, and Akt did not
      affect progranulin protein expression. CONCLUSIONS: These results suggest that
      the PKC signaling is involved in the regulation of progranulin protein expression
      in 2 different ovarian cancer cell lines. Inhibiting these intracellular signal
      transduction pathways may provide a future therapeutic target for hindering the
      cellular proliferation and invasion in ovarian cancer produced by progranulin.

PMID- 22665041
TI  - Diagnostic accuracy of magnetic resonance imaging in endometrial cancer.
AB  - OBJECTIVES: The objectives of this study were to investigate the accuracy of
      magnetic resonance imaging (MRI) in predicting the depth of myometrial invasion
      in the preoperative assessment of women with endometrial cancer and to quantify
      the impact of MRI as an adjunct to predicting patients requiring full surgical
      staging. METHODS: This was a diagnostic accuracy study of prospective cases in
      conjunction with STARD guidelines using collected data from a tumor board within
      a cancer network. Consecutive series of all endometrial cancers in Northern
      Ireland over a 21-month period was discussed at the Gynaecological Oncology
      Multidisciplinary Team/tumor board meeting. This study concerns 183 women who met
      all the inclusion criteria. Main outcome measure was the correlation between the
      depth of myometrial invasion suggested by preoperative MRI study and the
      subsequent histopathological findings following examination of the hysterectomy
      specimen. Secondary end point was how MRI changed management of women who
      required surgery to be performed at a central cancer center. RESULTS: For the
      detection of outer-half myometrial invasion, overall sensitivity of MRI was 0.73
      (95% confidence interval [CI], 0.59-0.83), and specificity was 0.83 (95% CI, 0.76
      0.89). The positive predictive value was 0.63 (95% CI, 0.50-0.74), and negative
      predictive value was 0.89 (95% CI, 0.82-0.93). Positive likelihood ratio was 4.35
      (95% CI, 2.87-6.61), and negative likelihood ratio was 0.33 (95% CI, 0.21-0.52).
      Magnetic resonance imaging improved the sensitivity and negative predictive value
      of endometrial biopsy alone in predicting women with endometrial cancer who
      require full surgical staging (0.73 vs 0.65 and 0.80 vs 0.78, respectively).
      CONCLUSIONS: Preoperative pelvic MRI is a moderately sensitive and specific
      method of identifying invasion to the outer half of myometrium in endometrial
      cancer. Addition of MRI to preoperative assessment leads to improved preoperative
      assessment, triage, and treatment.

PMID- 22665042
TI  - Intraperitoneal chemotherapy by ultrasound-guided direct puncture in recurrent
      ovarian cancer: feasibility, compliance, and complications.
AB  - OBJECTIVE: This prospective pilot study investigated the feasibility,
      complications, and compliance of the administration of intraperitoneal (IP)
      chemotherapy by direct puncture under ultrasonographic guidance performed on
      consecutive patients with recurrent ovarian cancer (ROC). METHODS: Patients were
      evaluated to undergo secondary cytoreduction and/or to receive IP chemotherapy.
      Patients received standard intravenous therapy for ROC plus IP administration by
      direct puncture needle, under ultrasonographic guidance. RESULTS: From January
      2008 to January 2011, 38 patients were enrolled. A total of 402 IP procedures
      were performed, with a mean of 10.5 procedures per patient. The feasibility rate
      was 97.4%. In 237 cases (98.8%) of subgroup 1 (abdominal wall thickness <=6 cm),
      the procedure was performed after 1 attempt, meanwhile in 6% of cases of subgroup
      2 (abdominal wall thickness >6 cm), more than 1 attempt was necessary (P < 0.01).
      The mean procedure time was 10 minutes (range, 5-30 minutes). We recorded a total
      of 2.25% mild intraprocedure complications. No significant difference was
      identified for the complication rate according to the abdominal wall thickness or
      according to the number of previous laparotomies. A total of 5 procedures (1.2%)
      were not performed as a result of patients' noncompliance. The mean pain score
      according to the visual analog pain scale was moderate at the first evaluation
      (after 3 minutes) and mild at the final evaluation (after 10 minutes).
      CONCLUSIONS: The administration of IP chemotherapy with a direct puncture, under
      ultrasound guidance, for patients with ROC, is a safe and feasible method, with a
      high acceptance from patients.

PMID- 22665043
TI  - Beyond picky eating: avoidant/restrictive food intake disorder.
AB  - Disorders related to ingesting adequate variety and amounts of food, often
      dichotomized into feeding or eating disorders, depending on the need for affected
      individuals to be fed or to eat on their own respectively, include a wide variety
      of conditions. This paper focuses on disorders that are not also associated with
      behaviors related to weight-control or self-concept strongly influenced by body
      weight or shape, as seen in anorexia nervosa or bulimia nervosa. In contrast to
      eating disorders, there is a relatively sparse body of literature, inconsistent
      and confusing set of terms and definitions, and conflicting classification
      schemes applied to feeding/eating disturbances. A new scheme is proposed to
      improve clinical utility and include individuals who experience morbidities that
      could benefit from diagnosis and treatment, but are presently excluded from
      classification. Key research findings are highlighted, and core clinical features
      regarding diagnosis and treatment are detailed. Two illustrative cases frame the
      clinical aspects of these conditions.

PMID- 22665046
TI  - Collection protocol for human pancreas.
AB  - This dissection and sampling procedure was developed for the Network for
      Pancreatic Organ Donors with Diabetes (nPOD) program to standardize preparation
      of pancreas recovered from cadaveric organ donors. The pancreas is divided into 3
      main regions (head, body, tail) followed by serial transverse sections throughout
      the medial to lateral axis. Alternating sections are used for fixed paraffin and
      fresh frozen blocks and remnant samples are minced for snap frozen sample
      preparations, either with or without RNAse inhibitors, for DNA, RNA, or protein
      isolation. The overall goal of the pancreas dissection procedure is to sample the
      entire pancreas while maintaining anatomical orientation. Endocrine cell
      heterogeneity in terms of islet composition, size, and numbers is reported for
      human islets compared to rodent islets. The majority of human islets from the
      pancreas head, body and tail regions are composed of insulin-containing beta
      cells followed by lower proportions of glucagon-containing alpha-cells and
      somatostatin-containing delta-cells. Pancreatic polypeptide-containing PP cells
      and ghrelin-containing epsilon cells are also present but in small numbers. In
      contrast, the uncinate region contains islets that are primarily composed of
      pancreatic polypeptide-containing PP cells. These regional islet variations arise
      from developmental differences. The pancreas develops from the ventral and dorsal
      pancreatic buds in the foregut and after rotation of the stomach and duodenum,
      the ventral lobe moves and fuses with the dorsal. The ventral lobe forms the
      posterior portion of the head including the uncinate process while the dorsal
      lobe gives rise to the rest of the organ. Regional pancreatic variation is also
      reported with the tail region having higher islet density compared to other
      regions and the dorsal lobe-derived components undergoing selective atrophy in
      type 1 diabetes. Additional organs and tissues are often recovered from the organ
      donors and include pancreatic lymph nodes, spleen and non-pancreatic lymph nodes.
      These samples are recovered with similar formats as for the pancreas with the
      addition of isolation of cryopreserved cells. When the proximal duodenum is
      included with the pancreas, duodenal mucosa may be collected for paraffin and
      frozen blocks and minced snap frozen preparations.

PMID- 22665047
TI  - Glutamate transporters and presynaptic metabotropic glutamate receptors protect
      neocortical Cajal-Retzius cells against over-excitation.
AB  - Cajal-Retzius (CR) cells, early generated neurons in the marginal zone of
      developing neocortex, are reported to be highly vulnerable to excitotoxic damage.
      Because extracellular glutamate concentration in the central nervous system is
      mainly controlled by glutamate transporters (EAATs), we studied the effects of
      EAAT blockade on CR cells. DL: -TBOA, a specific EAAT antagonist, induced NMDA
      receptor-dependent bursting discharges in layer 2/3 pyramidal neurons, indicating
      that EAATs operate in the uptake mode and their blockade leads to elevation of
      extracellular glutamate concentration. In CR cells, however, DL: -TBOA failed to
      change either the membrane resistance or holding current, and moreover, it
      reduced the frequency of spontaneous GABAergic postsynaptic currents. DL: -TBOA
      decreased the mean amplitude and increased paired-pulse ratio of evoked GABAergic
      postsynaptic currents, indicating the presynaptic locus of its action. Indeed,
      LY379268, a specific agonist of group II metabotropic glutamate receptors (mGluR
      II), mimicked the DL: -TBOA-mediated effects, and LY341495, an unspecific mGluR
      antagonist, eliminated the DL: -TBOA-induced effects. As dihydrokainic acid, a
      specific EAAT2 blocker, failed to affect evoked GABAergic postsynaptic currents,
      whereas TFB-TBOA, a selective blocker of EAAT1 and EAAT2, produced effects
      similar to that of DL: -TBOA, extracellular glutamate concentration in the
      marginal zone is mainly controlled by EAAT1 (GLAST). Thus, even though CR cells
      are highly vulnerable to excitotoxic damage, a number of mechanisms serve to
      protect them against excessive extracellular glutamate concentration including a
      lack of functional glutamatergic synapses, Mg(2+) blockade of NMDA receptors, and
      presynaptic mGluRs that inhibit transmission at GABAergic synapses.

PMID- 22665049
TI  - Periaqueductal gray matter modulates the hypercapnic ventilatory response.
AB  - The periaqueductal gray (PAG) is a midbrain structure directly involved in the
      modulation of defensive behaviors. It has direct projections to several central
      nuclei that are involved in cardiorespiratory control. Although PAG stimulation
      is known to elicit respiratory responses, the role of the PAG in the CO(2)-drive
      to breathe is still unknown. The present study assessed the effect of chemical
      lesion of the dorsolateral and dorsomedial and ventrolateral/lateral PAG (dlPAG,
      dmPAG, and vPAG, respectively) on cardiorespiratory and thermal responses to
      hypercapnia. Ibotenic acid (IBO) or vehicle (PBS, Sham group) was injected into
      the dlPAG, dmPAG, or vPAG of male Wistar rats. Rats with lesions outside the
      dlPAG, dmPAG, or vPAG were considered as negative controls (NC). Pulmonary
      ventilation (VE: ), mean arterial pressure (MAP), heart rate (HR), and body
      temperature (Tb) were measured in unanesthetized rats during normocapnia and
      hypercapnic exposure (5, 15, 30 min, 7 % CO(2)). IBO lesioning of the dlPAG/dmPAG
      caused 31 % and 26.5 % reductions of the respiratory response to CO(2) (1,094.3
      +/- 115 mL/kg/min) compared with Sham (1,589.5 +/- 88.1 mL/kg/min) and NC groups
      (1,488.2 +/- 47.7 mL/kg/min), respectively. IBO lesioning of the vPAG caused 26.6
      % and 21 % reductions of CO(2) hyperpnea (1,215.3 +/- 108.6 mL/kg/min) compared
      with Sham (1,657.3 +/- 173.9 mL/kg/min) and NC groups (1,537.6 +/- 59.3). Basal
      VE: , MAP, HR, and Tb were not affected by dlPAG, dmPAG, or vPAG lesioning. The
      results suggest that dlPAG, dmPAG, and vPAG modulate hypercapnic ventilatory
      responses in rats but do not affect MAP, HR, or Tb regulation in resting
      conditions or during hypercapnia.

PMID- 22665048
TI  - Tubular control of renin synthesis and secretion.
AB  - The intratubular composition of fluid at the tubulovascular contact site of the
      juxtaglomerular apparatus serves as regulatory input for secretion and synthesis
      of renin. Experimental evidence, mostly from in vitro perfused preparations,
      indicates an inverse relation between luminal NaCl concentration and renin
      secretion. The cellular transduction mechanism is initiated by concentration
      dependent NaCl uptake through the Na-K-2Cl cotransporter (NKCC2) with activation
      of NKCC2 causing inhibition and deactivation of NKCC2 causing stimulation of
      renin release. Changes in NKCC2 activity are coupled to alterations in the
      generation of paracrine factors that interact with granular cells. Among these
      factors, generation of PGE2 in a COX-2-dependent fashion appears to play a
      dominant role in the stimulatory arm of tubular control of renin release. [NaCl]
      is a determinant of local PG release over an appropriate concentration range, and
      blockade of COX-2 activity interferes with the NaCl dependency of renin
      secretion. The complex array of local paracrine controls also includes nNOS
      mediated synthesis of nitric oxide, with NO playing the role of a modifier of the
      intracellular signaling pathway. A role of adenosine may be particularly
      important when [NaCl] is increased, and at least some of the available evidence
      is consistent with an important suppressive effect of adenosine at higher salt
      concentrations.

PMID- 22665050
TI  - SVCT-2 in breast cancer acts as an indicator for L-ascorbate treatment.
AB  - L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on
      cancer cells. However, the mechanism underlying differential sensitivity of
      cancer cells from same tissue to L-ascorbate is yet to be clarified. Here, we
      demonstrate that L-ascorbate has a selective killing effect, which is influenced
      by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer
      cells. Treatment of human breast cancer cells with L-ascorbate differentially
      induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of
      endogenous SVCT-2 via RNA interference in breast cancer cells expressing high
      levels of the protein induced resistance to L-ascorbate treatment, whereas
      transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate
      chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in
      mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level.
      Interestingly, SVCT-2 expression was absent or weak in normal tissues, but
      strongly detected in tumor samples obtained from breast cancer patients. In
      addition, enhanced chemosensitivity to L-ascorbate occurred as a result of
      caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In
      addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS)
      scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the
      differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to
      intracellular ROS induced by L-ascorbate, subsequently leading to autophagy.
      These results suggest that functional SVCT-2 sensitizes breast cancer cells to
      autophagic damage by increasing the L-ascorbate concentration and intracellular
      ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator
      for commencing L-ascorbate treatment.

PMID- 22665051
TI  - Maintenance of acinar cell organization is critical to preventing Kras-induced
      acinar-ductal metaplasia.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers owing
      to a number of characteristics including difficulty in establishing early
      diagnosis and the absence of effective therapeutic regimens. A large number of
      genetic alterations have been ascribed to PDAC with mutations in the KRAS2 proto
      oncogene thought to be an early event in the progression of disease. Recent
      lineage-tracing studies have shown that acinar cells expressing mutant Kras(G12D)
      are induced to transdifferentiate, generating duct-like cells through a process
      known as acinar-ductal metaplasia (ADM). ADM lesions then convert to precancerous
      pancreatic intraepithelial neoplasia (PanIN) that progresses to PDAC over time.
      Thus, understanding the earliest events involved in ADM/PanIN formation would
      provide much needed information on the molecular pathways that are instrumental
      in initiating this disease. As studying the transition of acinar cells to
      metaplastic ductal cells in vivo is complicated by analysis of the entire organ,
      an in vitro three dimensional (3D) culture system was used to model ADM outside
      the animal. Kras(G12D)-expressing acinar cells rapidly underwent ADM in 3D
      culture, forming ductal cysts that silenced acinar genes and activated duct
      genes, characteristics associated with in vivo ADM/PanIN lesions. Analysis of
      downstream KRAS signaling events established a critical importance for the
      Raf/MEK/ERK pathway in ADM induction. In addition, forced expression of the
      acinar-restricted transcription factor Mist1, which is critical to acinar cell
      organization, significantly attenuated Kras(G12D)-induced ADM/PanIN formation.
      These results suggest that maintaining MIST1 activity in Kras(G12D)-expressing
      acinar cells can partially mitigate the transformation activity of oncogenic
      KRAS. Future therapeutics that target both the MAPK pathway and Mist1
      transcriptional networks may show promising efficacy in combating this deadly
      disease.

PMID- 22665052
TI  - TGF-beta-induced apoptosis of B-cell lymphoma Ramos cells through reduction of
      MS4A1/CD20.
AB  - Transforming growth factor-beta (TGF-beta) exhibits growth inhibitory effects on
      various types of tumor cells, including B-cell lymphoma cells. In the present
      study, the role of TGF-beta in the survival of Epstein-Barr virus-negative B-cell
      lymphoma Ramos cells was investigated. As TGF-beta-induced apoptosis of Ramos
      cells in vitro and in vivo, we attempted to identify novel target gene(s)
      responsible for their survival. Oligonucleotide microarray analysis and chromatin
      immunoprecipitation revealed that Smad proteins directly regulated the
      transcription of membrane-spanning 4-domains, subfamily A, member 1 (MS4A1), also
      known as CD20, in Ramos cells upon TGF-beta stimulation. In addition,
      immunohistochemical analysis using clinical samples from B-cell lymphoma patients
      showed an inverse correlation between the expression of MS4A1/CD20 and
      phosphorylation of Smad3. Although knockdown of MS4A1/CD20 in Ramos cells
      resulted in an increase of apoptotic cells, Ramos cells stably expressing
      MS4A1/CD20 were resistant to TGF-beta-induced apoptosis. This suggests that
      MS4A1/CD20 is responsible for TGF-beta-induced apoptosis of B-cell lymphoma
      cells. Moreover, downregulation of MS4A1/CD20 by TGF-beta attenuated the effects
      of the monoclonal anti-MS4A1/CD20 antibody, rituximab, on Ramos cells. Our
      findings suggest that the sensitivity of B-cell lymphoma cells to rituximab may
      be affected by TGF-beta signaling.

PMID- 22665053
TI  - Targeting metabolism for cancer treatment and prevention: metformin, an old drug
      with multi-faceted effects.
AB  - Understanding the complexity of cancer and of the underlying regulatory networks
      provides a new paradigm that tackles cancer development and treatment through a
      system biology approach, contemporarily acting on various intersecting pathways.
      Cancer cell metabolism is an old pathogenetic issue that has recently gained new
      interest as target for therapeutic approaches. More than 70 years ago, Warburg
      discovered that malignant cells generally have altered metabolism with high rates
      of glucose uptake and increased glycolysis, even under aerobic condition.
      Observational studies have provided evidence that impaired metabolism, obesity,
      hyperglycemia and hyperinsulinemia may have a role in cancer development,
      progression and prognosis, and actually diabetic and obese patients have
      increased cancer risk. On the other hand, caloric restriction has been shown to
      prolong life span and reduce cancer incidence in several animal models, having an
      impact on different metabolic pathways. Metformin, an antidiabetic drug widely
      used for over 40 years, mimics caloric restriction acting on cell metabolism at
      multiple levels, reducing all energy-consuming processes in the cells, including
      cell proliferation. By overviewing molecular mechanisms of action,
      epidemiological evidences, experimental data in tumor models and early clinical
      study results, this review provides information supporting the promising use of
      metformin in cancer prevention and treatment.

PMID- 22665054
TI  - Stathmin 1 is a potential novel oncogene in melanoma.
AB  - In previous studies, we demonstrated that miR-193b expression is reduced in
      melanoma relative to benign nevi, and also that miR-193b represses cyclin D1 and
      Mcl-1 expression. We suggested that stathmin 1 (STMN1) might be a target of miR
      193b. STMN1 normally regulates microtubule dynamics either by sequestering free
      tubulin heterodimers or by promoting microtubule catastrophe. Increased
      expression of STMN1 has been observed in a variety of human malignancies, but its
      association with melanoma is unknown. We now report that STMN1 is upregulated
      during the progression of melanoma relative to benign nevi, and that STMN1 is
      directly regulated by miR-193b. Using an experimental cell culture approach,
      overexpression of miR-193b using synthetic microRNAs repressed STMN1 expression,
      whereas inhibition of miR-193b with anti-miR oligos increased STMN1 expression in
      melanoma cells. The use of a luciferase reporter assay confirmed that miR-193b
      directly regulates STMN1 by targeting the 3'-untranslated region of STMN1 mRNA.
      We further demonstrated that STMN1 is overexpressed in malignant melanoma
      compared with nevi in two independent melanoma cohorts, and that its level is
      inversely correlated with miR-193b expression. However, STMN1 expression was not
      significantly associated with patient survival, Breslow depth, mitotic count or
      patient age. STMN1 knockdown by small-interfering RNA in melanoma cells
      drastically repressed cell proliferation and migration potential, whereas ectopic
      expression of STMN1 using lentivirus increased cell proliferation and migration
      rates. Subsequent gene expression analysis indicated that interconnected
      cytoskeletal networks are directly affected following STMN1 knockdown. In
      addition, we identified deregulated genes associated with proliferation and
      migration, and revealed that p21(Cip1/Waf1) and p27(Kip) could be downstream
      effectors of STMN1 signaling. Taken together, our study suggests that
      downregulation of miR-193b may contribute to increased STMN1 expression in
      melanoma, which consequently promotes migration and proliferation of tumor cells.

PMID- 22665055
TI  - Regulation of glycolysis and the Warburg effect by estrogen-related receptors.
AB  - Cancer cells typically display altered glucose metabolism characterized by a
      preference of aerobic glycolysis, known as the Warburg effect, which facilitates
      cell proliferation. Hypoxia-inducible factor (HIF) and oncoprotein Myc are two
      prominent transcription factors that drive glycolysis. Previously, we reported
      that the estrogen-related receptors (ERRs) act as cofactors of HIF and enhance
      HIF-dependent transcription of glycolytic genes under hypoxia. ERRs are orphan
      nuclear receptors and key regulators of energy metabolism by orchestrating
      mitochondrial biogenesis, fatty acid oxidation (FAO) and oxidative
      phosphorylation. Here, we show that ERRs also stimulate glycolysis under
      normoxia. ERRs directly bind to and activate promoters of many genes encoding
      glycolytic enzymes, and the ERR-binding sites in such promoters are essential for
      ERR-mediated transcriptional activation. ERRs interact with Myc, and the two
      factors synergistically activate transcription of glycolytic genes. Furthermore,
      overexpression of ERRs increases glycolytic gene expression and lactate
      production. Conversely, depletion of ERRs in cancer cells reduces expression of
      glycolytic genes and glucose uptake, resulting in decreased aerobic glycolysis
      and cell growth. Taken together, these results suggest that ERRs are important
      transcriptional activators of the glycolytic pathway and contribute to the
      Warburg effect in cancer cells.

PMID- 22665056
TI  - The aryl hydrocarbon receptor regulates focal adhesion sites through a non
      genomic FAK/Src pathway.
AB  - The aryl hydrocarbon receptor (AhR) is commonly described as a transcription
      factor, which regulates xenobiotic-metabolizing enzymes. Recent studies have
      suggested that the binding of ligands to the AhR also activates the Src kinase.
      In this manuscript, we show that the AhR, through the activation of Src,
      activates focal adhesion kinase (FAK) and promotes integrin clustering. These
      effects contribute to cell migration. Further, we show that the activation of the
      AhR increases the interaction of FAK with the metastatic marker, HEF1/NEDD9/CAS
      L, and the expression of several integrins. Xenobiotic exposure, thus, may
      contribute to novel cell-migratory programs.

PMID- 22665057
TI  - RhoD participates in the regulation of cell-cycle progression and centrosome
      duplication.
AB  - We have previously identified a Rho protein, RhoD, which localizes to the plasma
      membrane and the early endocytic compartment. Here, we show that a GTPase
      deficient mutant of RhoD, RhoDG26V, causes hyperplasia and perturbed
      differentiation of the epidermis, when targeted to the skin of transgenic mice.
      In vitro, gain-of-function and loss-of-function approaches revealed that RhoD is
      involved in the regulation of G1/S-phase progression and causes overduplication
      of centrosomes. Centriole overduplication assays in aphidicolin-arrested p53
      deficient U2OS cells, in which the cell and the centrosome cycles are uncoupled,
      revealed that the effects of RhoD and its mutants on centrosome duplication and
      cell cycle are independent. Enhancement of G1/S-phase progression was mediated
      via Diaph1, a novel effector of RhoD, which we have identified using a two-hybrid
      screen. These results indicate that RhoD participates in the regulation of cell
      cycle progression and centrosome duplication.

PMID- 22665058
TI  - Acute WNT signalling activation perturbs differentiation within the adult stomach
      and rapidly leads to tumour formation.
AB  - A role for WNT signalling in gastric carcinogenesis has been suggested due to two
      major observations. First, patients with germline mutations in adenomatous
      polyposis coli (APC) are susceptible to stomach polyps and second, in gastric
      cancer, WNT activation confers a poor prognosis. However, the functional
      significance of deregulated WNT signalling in gastric homoeostasis and cancer is
      still unclear. In this study we have addressed this by investigating the
      immediate effects of WNT signalling activation within the stomach epithelium. We
      have specifically activated the WNT signalling pathway within the mouse adult
      gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or
      APC or via expression of a constitutively active beta-catenin protein. WNT
      pathway deregulation dramatically affects stomach homoeostasis at very short
      latencies. In the corpus, there is rapid loss of parietal cells with fundic gland
      polyp (FGP) formation and adenomatous change, which are similar to those observed
      in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post
      WNT activation. Taken together, these data show a pivotal role for WNT signalling
      in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal
      cell population and corresponding FGP formation, an early event in gastric
      carcinogenesis, as well as antral adenoma formation are immediate effects of
      nuclear beta-catenin translocation and WNT target gene expression. Furthermore,
      our inducible murine model will permit a better understanding of the molecular
      changes required to drive tumourigenesis in the stomach.

PMID- 22665059
TI  - Neutrophil chemokines secreted by tumor cells mount a lung antimetastatic
      response during renal cell carcinoma progression.
AB  - The mechanism by which renal cell carcinoma (RCC) colonizes the lung
      microenvironment during metastasis remains largely unknown. To investigate this
      process, we grafted human RCC cells with varying lung metastatic potential in
      mice. Gene expression profiling of the mouse lung stromal compartment revealed a
      signature enriched for neutrophil-specific functions that was induced
      preferentially by poorly metastatic cells. Analysis of the gene expression
      signatures of tumor cell lines showed an inverse correlation between metastatic
      activity and the levels of a number of chemokines, including CXCL5 and IL8.
      Enforced depletion of CXCL5 and IL8 in these cell lines enabled us to establish a
      functional link between lung neutrophil infiltration, secretion of chemokines by
      cancer cells and metastatic activity. We further show that human neutrophils
      display a higher cytotoxic activity against poorly metastatic cells compared with
      highly metastatic cells. Together, these results support a model in which
      neutrophils recruited to the lung by tumor-secreted chemokines build an
      antimetastatic barrier with loss of neutrophil chemokines in tumor cells acting
      as a critical rate-limiting step during lung metastatic seeding.

PMID- 22665060
TI  - Nuclear import of LASP-1 is regulated by phosphorylation and dynamic protein
      protein interactions.
AB  - LASP-1 is a multidomain protein predominantly localized at focal contacts, where
      it regulates cytoskeleton dynamics and cell migration. However, in different
      tumor entities, a nuclear LASP-1 accumulation is observed, thought to have an
      important role in cancer progression. Until now, the molecular mechanisms that
      control LASP-1 nuclear import were not elucidated. Here, we identified a novel
      LASP-1-binding partner, zona occludens protein 2 (ZO-2), and established its role
      in the signal transduction pathway of LASP-1 nucleo-cytoplasmatic shuttling.
      Phosphorylation of LASP-1 by PKA at serine 146 induces translocation of the LASP
      1/ZO-2 complex from the cytoplasm to the nucleus. Interaction occurs within the
      carboxyterminal proline-rich motif of ZO-2 and the SH3 domain in LASP-1. In situ
      proximity ligation assay confirmed the direct binding between LASP-1 and ZO-2 and
      visualized the shuttling. Nuclear export is mediated by Crm-1 and a newly
      identified nuclear export signal in LASP-1. Finally, dephosphorylation of LASP-1
      by phosphatase PP2B is suggested to relocalize the protein back to focal
      contacts. In summary, we define a new pathway for LASP-1 in tumor progression.

PMID- 22665061
TI  - The p44/wdr77-dependent cellular proliferation process during lung development is
      reactivated in lung cancer.
AB  - During lung development, cells proliferate for a defined length of time before
      they begin to differentiate. Factors that control this proliferative process and
      how this growth process is related to lung cancer are currently unknown. Here, we
      found that the WD40-containing protein (p44/wdr77) was expressed in growing
      epithelial cells at the early stages of lung development. In contrast, p44/wdr77
      expression was diminished in fully differentiated epithelial cells in the adult
      lung. Loss of p44/wdr77 gene expression led to cell growth arrest and
      differentiation. Re-expression of p44/wdr77 caused terminally differentiated
      cells to re-enter the cell cycle. Our findings suggest that p44/wdr77 is
      essential and sufficient for proliferation of lung epithelial cells. P44/Wdr77
      was re-expressed in lung cancer, and silencing p44/wdr77 expression strongly
      inhibited growth of lung adenocarcinoma cells in tissue culture and abolished
      growth of lung adenocarcinoma tumor xenografts in mice. The growth arrest induced
      by loss of p44/wdr77 expression was partially through the p21-Rb signaling. Our
      results suggest that p44/wdr77 controls cellular proliferation during lung
      development, and this growth process is reactivated during lung tumorigenesis.

PMID- 22665062
TI  - Nucleophosmin is essential for c-Myc nucleolar localization and c-Myc-mediated
      rDNA transcription.
AB  - The transcription factor c-Myc has a critical role in cell proliferation and
      growth. The control of ribosome biogenesis by c-Myc through the regulation of
      transcription mediated by all three RNA polymerases is essential for c-Myc-driven
      proliferation. Specifically, in the nucleolus, c-Myc has been shown to be
      recruited to ribosomal DNA and activate RNA polymerase (pol) I-mediated
      transcription of ribosomal RNA (rRNA) genes. In addition, c-Myc accumulates in
      nucleoli upon inhibition of the proteasome, suggesting nucleolar localization
      also has a role in c-Myc proteolysis. Nucleophosmin (NPM), a predominantly
      nucleolar protein, is also critical in ribosome biogenesis and, like c-Myc, is
      found overexpressed in many types of tumors. Previously, we demonstrated that NPM
      directly interacts with c-Myc and controls c-Myc-induced hyperproliferation and
      transformation. Here, we show that NPM is necessary for the localization of c-Myc
      protein to nucleoli, whereas c-Myc nucleolar localization is independent of p53,
      Mdm2 and ARF. Conversely, high transient NPM expression enhances c-Myc nucleolar
      localization, leading to increased c-Myc proteolysis. In addition, NPM is
      necessary for the ability of c-Myc to induce rRNA synthesis in the nucleolus, and
      constitutive NPM overexpression stimulates c-Myc-mediated rRNA synthesis. Taken
      together, these results demonstrate an essential role for NPM in c-Myc nucleolar
      localization and c-Myc-mediated rDNA transcription.

PMID- 22665063
TI  - Beta-catenin inhibits melanocyte migration but induces melanoma metastasis.
AB  - The canonical Wnt signalling pathway induces the beta-catenin/lymphoid enhancer
      factor transcription factors. It is activated in various cancers, most
      characteristically carcinomas, in which it promotes metastatic spread by
      increasing migration and/or invasion. The Wnt/beta-catenin signalling pathway is
      frequently activated in melanoma, but the presence of beta-catenin in the nucleus
      does not seem to be a sign of aggressiveness in these tumours. We found that,
      unlike its positive role in stimulating migration and invasion of carcinoma
      cells, beta-catenin signalling decreased the migration of melanocytes and
      melanoma cell lines. In vivo, beta-catenin signalling in melanoblasts reduced the
      migration of these cells, causing a white belly-spot phenotype. The inhibition by
      beta-catenin of migration was dependent on MITF-M, a key transcription factor of
      the melanocyte lineage, and CSK, an Src-inhibitor. Despite reducing migration,
      beta-catenin signalling promoted lung metastasis in the NRAS-driven melanoma
      murine model. Thus, beta-catenin may have conflicting roles in the metastatic
      spread of melanoma, repressing migration while promoting metastasis. These
      results highlight that metastasis formation requires a series of successful
      cellular processes, any one of which may not be optimally efficient.

PMID- 22665065
TI  - Opposing functions of Fbxw7 in keratinocyte growth, differentiation and skin
      tumorigenesis mediated through negative regulation of c-Myc and Notch.
AB  - The tumor suppressor Fbxw7 (also known as Sel-10, hCdc4, hAgo, or Fbw7) is an F
      box protein that functions as the substrate-recognition subunit of an SCF
      ubiquitin ligase complex and targets a group of oncoproteins for degradation. We
      now show that Fbxw7 regulates the proliferation and differentiation of
      keratinocytes by mediating the degradation of c-Myc and Notch proteins. Fbxw7
      deficient keratinocytes showed an increased proliferative capacity that was
      dependent on the accumulation of c-Myc but not on that of Notch. Fbxw7 deficiency
      also resulted in the premature differentiation of keratinocytes in a manner
      dependent on both c-Myc and Notch. Although Fbxw7-deficient keratinocytes
      proliferated excessively in vitro, loss of Fbxw7 did not predispose keratinocytes
      to the formation of squamous cell carcinoma in vivo induced by the expression of
      oncogenic Ras, possibly because the stem cell population of keratinocytes becomes
      exhausted as a result of enhanced Notch activity. Indeed, suppression of Notch
      signaling by additional ablation of RBP-J in Fbxw7-deficient keratinocytes
      conferred a more aggressive tumorigenic capacity. Collectively, these results
      indicate that Fbxw7 controls the proliferation and differentiation of
      keratinocytes, and that it exerts both inhibitory and stimulatory actions in skin
      carcinogenesis by counteracting the proliferation-promoting effect of c-Myc and
      the tumor-suppressive effect of Notch, respectively.

PMID- 22665066
TI  - BCR-ABL regulates death receptor expression for TNF-related apoptosis-inducing
      ligand (TRAIL) in Philadelphia chromosome-positive leukemia.
AB  - Allogeneic stem cell transplantation (allo-SCT) is a potentially curative therapy
      for chronic myeloid leukemia and Philadelphia chromosome-positive (Ph(+)) acute
      lymphoblastic leukemia, and the graft-vs-leukemia (GVL) effect can eradicate
      residual leukemia after allo-SCT. Ph(+) leukemia cells frequently express death
      inducing receptors (DR4 and DR5) for tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL), which is one of the cytotoxic ligands expressed on
      cytotoxic T cells and natural killer cells mediating the GVL effect. Here we
      demonstrate that imatinib specifically downregulated DR4 and DR5 expression in
      cell lines and clinical samples of Ph(+) leukemia. Second-generation tyrosine
      kinase inhibitors (dasatinib and nilotinib) and short hairpin RNA against bcr-abl
      also downregulated DR4 and DR5 expression in Ph(+) leukemia cells, and
      transfection of bcr-abl into a Ph(-) leukemia cell line induced DR4 and DR5
      expression, which was abrogated by imatinib treatment. Accordingly, Ph(+)
      leukemia cells that had been pretreated with imatinib showed resistance to the
      pro-apoptotic activity of recombinant human soluble TRAIL. These observations
      demonstrate that BCR-ABL is critically involved in the leukemia-specific
      expression of DR4 and DR5 and in the susceptibility of Ph(+) leukemia to TRAIL
      mediated anti-leukemic activity, providing new insight into the mechanisms of the
      tumor-specific cytotoxic activities of TRAIL.

PMID- 22665064
TI  - The deubiquitylase USP37 links REST to the control of p27 stability and cell
      proliferation.
AB  - The RE1 silencing transcription factor (REST) is a repressor of neuronal
      differentiation and its elevated expression in neural cells blocks neuronal
      differentiation. In this study, we demonstrate a role for REST in the control of
      proliferation of medulloblastoma cells. REST expression decreased the levels of
      cyclin-dependent kinase (CDK)NIB/p27, a CDK inhibitor and a brake of cell
      proliferation in these cells. The reciprocal relationship between REST and p27
      was validated in human tumor samples. REST knockdown in medulloblastoma cells
      derepessed a novel REST target gene encoding the deubiquitylase ubiquitin (Ub)
      specific peptidase 37 (USP37). Ectopically expressed wild-type USP37 formed a
      complex with p27, promoted its deubiquitination and stabilization and blocked
      cell proliferation. Knockdown of REST and USP37 prevented p27 stabilization and
      blocked the diminution in proliferative potential that normally accompanied REST
      loss. Unexpectedly, wild-type USP37 expression also induced the expression of
      REST-target neuronal differentiation genes even though REST levels were
      unaffected. In contrast, a mutant of USP37 carrying a site-directed change in a
      conserved cysteine failed to rescue REST-mediated p27 destabilization,
      maintenance of cell proliferation and blockade to neuronal differentiation.
      Consistent with these findings, a significant correlation between USP37 and p27
      was observed in patient tumors. Collectively, these findings provide a novel
      connection between REST and the proteasomal machinery in the control of p27 and
      cell proliferation in medulloblastoma cells.

PMID- 22665067
TI  - Akt1 inhibits homologous recombination in Brca1-deficient cells by blocking the
      Chk1-Rad51 pathway.
AB  - Brca1 deficiency leads to the development of breast cancer. We previously found
      that Brca1 deficiency activates the Akt oncogenic pathway. Reduced expression of
      Brca1 was highly correlated with increased activated Akt in human breast cancer
      samples. Furthermore, activation of Akt1 was involved in Brca1-deficiency
      mediated tumorigenesis in mice. Defective homologous recombination (HR) is
      thought to be a major contributor to tumorigenesis in Brca1 deficiency. Here, we
      show that Akt1 promotes chromosome instability in Brca1-deficent cells. DNA
      breaks in Brca1-deficent cells are aberrantly joined into complex chromosome
      rearrangements by a process dependent on Akt1. Depletion of Akt1 increases HR in
      Brca1-mutant cells, which is rescued by expression of wild-type, but not mutant
      Akt1 with deletion of Brca1-binding domain. Mechanistically, activated Akt1 in
      Brca1-deficient cells impairs Chk1 nuclear localization and subsequently disrupts
      interaction of Chk1 and Rad51 leading to HR defects. Our results indicate that
      Brca1 deficiency might activate Akt1 contributing to tumorigenesis through
      regulation of the Chk1-Rad51 signaling.

PMID- 22665068
TI  - Retinal breaks in vitrectomy for retained lens fragments.
AB  - PURPOSE: To describe the incidence and outcome of retinal breaks in vitrectomy
      for retained lens fragments. METHODS: This is a retrospective noncomparative
      interventional case series. Medical records of consecutive cases of vitrectomy
      for retained lens fragments over a period of 4 years were reviewed. Main outcome
      measures were incidence of breaks, visual acuity outcome, and occurrence of
      postoperative complications. RESULTS: We included 89 consecutive cases in 89
      patients. The median interval between cataract surgery and vitrectomy was 2 days
      (range, 0-106 days). Visual acuity at last follow-up was >= 0.5 in 70% of cases.
      During surgery, retinal breaks were found in 29% of cases. Induction of a
      posterior vitreous detachment, the use of a fragmatome, or delay between cataract
      surgery and vitrectomy did not influence retinal break incidence. Postoperative
      retinal detachment occurred in only 2% of cases. Other complications were
      intraoperative choroidal hemorrhage in 1 case, postoperative macular pucker in 2,
      postoperative macular edema in 1, and glaucoma in 2 cases. CONCLUSION: We
      identified a high number of retinal breaks during vitrectomy for retained lens
      fragments. Prophylactic treatment of breaks and other areas of retinal traction
      seem to reduce the risk of postoperative retinal detachment.

PMID- 22665070
TI  - Loop diuretic use at discharge is associated with adverse outcomes in
      hospitalized patients with heart failure: a report from the Japanese cardiac
      registry of heart failure in cardiology (JCARE-CARD).
AB  - BACKGROUND: Loop diuretics are commonly used in patients with heart failure (HF)
      to remove retained fluid and improve symptoms. However, they may potentially
      worsen outcomes in HF. It remains unknown whether the use of loop diuretics is
      associated with adverse HF outcomes in routine clinical practice. We thus
      determined the effects of loop diuretic use at discharge on long-term mortality
      and rehospitalization among patients hospitalized with HF. METHODS AND RESULTS:
      The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD)
      prospectively studied the characteristics and treatments of a broad sample of
      patients hospitalized with worsening HF and followed for 2.1 years. Among a total
      of 2,549 HF patients, loop diuretics were used by 2,015 patients (79%), but not
      534 patients (21%). The mean age was 70.7 years and 60% were male. Etiology was
      ischemic in 32% and mean left ventricular ejection fraction was 42%. After
      adjustment for covariates, discharge use of loop diuretics was associated with
      significant adverse risks of cardiac death (adjusted hazard ratio [HR] 2.348, 95%
      confidence interval [CI] 1.246-4.423, P=0.008) and rehospitalization (adjusted HR
      1.427, 95% CI 1.040-1.959, P=0.027). CONCLUSIONS: Among patients hospitalized
      with worsening HF, loop diuretic use at discharge was associated with long-term
      adverse outcomes, which suggests that routine chronic use of loop diuretics may
      be harmful for patients with HF.

PMID- 22665069
TI  - Correlation of ADCC activity with cytokine release induced by the stably
      expressed, glyco-engineered humanized Lewis Y-specific monoclonal antibody MB314.
AB  - A major limitation to the application of therapeutic monoclonal antibodies (mAbs)
      is their reduced in vivo efficacy compared with the high efficacy measured in
      vitro. Effector functions such as antibody-dependent cell-mediated cytotoxicity
      (ADCC) are dramatically reduced in vivo by the presence of high amounts of
      endogenous IgG in the serum. Recent studies have shown that modification of the
      glycosylation moieties attached to the Fc part of the mAb can enhance binding
      affinity to FcgammaRIIIalpha receptors on natural killer cells and thus may
      counteract the reduced in vivo efficacy. In the present study, a humanized
      IgG1/kappa monoclonal antibody recognizing the tumor-associated carbohydrate
      antigen Lewis Y was stably produced in a moss expression system that allows glyco
      engineering. The glyco-modified mAb (designated MB314) showed a highly
      homogeneous N-glycosylation pattern lacking core-fucose. A side-by-side
      comparison to its parental counterpart produced in conventional mammalian cell
      culture (MB311, formerly known as IGN311) by fluorescence-activated cell sorting
      analysis confirmed that the target specificity of MB314 is similar to that of
      MB311. In contrast, ADCC effector function of MB314 was increased up to 40-fold
      whereas complement dependent cytotoxicity activity was decreased 5-fold. Notably,
      a release of immunostimulatory cytokines, including interferon gamma, monocyte
      chemotactic protein-1 (MCP-1), interleukin-6 and tumor necrosis factor (TNF) was
      particularly induced with the glyco-modified antibody. TNF release was associated
      with CD14 (+)  cells, indicating activation of monocytes.

PMID- 22665072
TI  - Is magnetic resonance imaging of right ventricular volume useful clinically for
      evaluation of pulmonary arterial hypertension?

PMID- 22665071
TI  - Prevalence of inherited thrombophilia in patients with documented stent
      thrombosis.
AB  - BACKGROUND: Stent thrombosis (ST) is a multi-factorial process involving
      different mechanisms. The impact of inherited coagulation disorders in the
      genesis of ST has never been assessed. The aim of the present study was to
      evaluate the prevalence of G1691A Factor V Leiden mutation, G20210A Factor II
      (prothrombin) mutation and C677T homozygous methylenetetrahydrofolate reductase
      (MTHFR) polymorphism in patients with ST. METHODS AND RESULTS: The prevalence of
      the aforementioned gene variations was assessed in 127 patients: 50 admitted for
      ST and 77 previously treated with percutaneous coronary intervention not
      developing ST. A control cohort of 529 healthy volunteers was sampled from the
      same geographical area. Patients with ST were carriers of at least 1 gene
      variation in 28% of cases. The prevalence of G1691A Factor V Leiden mutation
      (odds ratio [OR]=0.64; 95% confidence interval [CI]: 0.04-10.5), G20210A Factor
      II mutation (OR=0.63; 95% CI: 0.12-3.28) and C677T MTHFR homozygous polymorphism
      (OR=1.13; 95% CI: 0.47-2.72) did not differ significantly among patients with or
      without ST. The logistic regression model did not show a significant association
      between gene variations and ST (OR=0.61; 95% CI: 0.24-1.60; P=0.32). CONCLUSIONS:
      A specific association between studied gene variations and ST has not been
      detected. The relatively high prevalence of at least 1 gene anomaly in such a
      rare subset of patients, and its consequences in term of secondary prevention
      therapy, suggests that screening for thrombophilia might be justifiable in cases
      of ST.

PMID- 22665073
TI  - Percutaneous core needle biopsy for small (<= 10 mm) lung nodules: accurate
      diagnosis and complication rates.
AB  - PURPOSE: To evaluate accurate diagnosis and complication rates of percutaneous
      core needle biopsy (PCNB) with an automated gun for small lung nodules that are
      10 mm or less in diameter. MATERIALS AND METHODS: Forty-two cases of small lung
      nodules with diameters <= 10 mm (mean diameter, 9 mm) that received a PCNB were
      included in this study. Imaging guidance was fluoroscopy in 30 cases and computed
      tomography (CT) in 12 cases. RESULTS: Accurate diagnosis was achieved with the
      initial PCNB in 88.1% (37/42) of cases. Accurate diagnosis rates were 86.7%
      (26/30) with fluoroscopic guidance and 91.7% (11/12) with CT guidance (P > 0.05).
      The complication rate of PCNB was 7.1% (3/42), including hemoptysis (n=2) and
      pneumothorax (n=1). The complication rate was 6.7% (2/30) with fluoroscopic
      guidance and 8.3% (1/12) with CT guidance (P > 0.05). CONCLUSION PCNB: with an
      automated gun is useful for the pathologically conclusive diagnosis of small lung
      nodules (<= 10 mm in diameter) using fluoroscopic or CT guidance.

PMID- 22665074
TI  - The relevance of electroencephalogram as a follow-up test in Hashimoto
      encephalopathy course after corticosteroids therapy.

PMID- 22665075
TI  - Epileptologists in quest for the Holy Grail.

PMID- 22665076
TI  - The impact of the San Diego wildfires on a general mental health population
      residing in evacuation areas.
AB  - San Diego County Mental Health system clients completed a questionnaire after the
      October 2007 wildfires. As compared to those not in an evacuation area, those
      residing in an evacuation area reported significantly more impact of the fires.
      Clients who evacuated were most affected, followed by those in an evacuation area
      who did not evacuate. Evacuation strongly impacted client-reported emotional
      effects of the fire, confusion about whether to evacuate, and ability to obtain
      medications. Gender and clinical diagnosis interacted with evacuation status for
      some fire impact variables. Loss of control and disruption of routine are
      discussed as possibly related factors. 

PMID- 22665077
TI  - Wogonin potentiates cisplatin-induced cancer cell apoptosis through accumulation
      of intracellular reactive oxygen species.
AB  - Chemoresistance to cisplatin is a major limitation of cisplatin-based
      chemotherapy in the clinic. The combination of cisplatin with other agents has
      been recognized as a promising strategy to overcome cisplatin resistance.
      Previous studies have shown that wogonin (5,7-dihydroxy-8-methoxyflavone), a
      flavonoid isolated from the root of the medicinal herb Scutellaria baicalensis
      Georgi, sensitizes cancer cells to chemotheraputics such as etoposide,
      adriamycin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and
      TNF. However, the effect of wogonin on cisplatin-induced cytotoxicity has not
      been previously reported. In this study, the non-small cell lung cancer cell line
      A549 and the cervical cancer cell line HeLa were treated with wogonin or
      cisplatin individually or in combination. It was found for the first time that
      wogonin is able to sensitize cisplatin-induced apoptosis in both A549 cells and
      HeLa cells as indicated by the potentiation of activation of caspase-3, and
      cleavage of the caspase-3 substrate PARP in wogonin and cisplatin co-treated
      cells. Importantly, wogonin robustly induced H2O2 accumulation in these cells,
      which substantially contributes to the sensitization of cisplatin cytotoxicity by
      wogonin, as two reactive oxygen species scavengers, butylated hydroxyanisole
      (BHA) and N-acetyl-L-cysteine (NAC), significantly suppressed the potentiated
      cytotoxicity caused by wogonin and cisplatin co-treatment. The results from this
      study provide important new evidence supporting the potential use of wogonin as a
      cisplatin sensitizer for cancer therapy.

PMID- 22665080
TI  - The cover. Dimensions of global health, 2012.

PMID- 22665083
TI  - Recent advances in mobile technology benefit global health, research, and care.

PMID- 22665084
TI  - IOM report lays out a blueprint for improving regulatory systems worldwide.

PMID- 22665089
TI  - Breast cancer mortality and age at diagnosis.

PMID- 22665091
TI  - Time spent sedentary and active and cardiometabolic risk factors in children.

PMID- 22665093
TI  - Specialization in health care.

PMID- 22665094
TI  - Specialization in health care.

PMID- 22665095
TI  - Specialization in health care.

PMID- 22665097
TI  - Changes in prevalence of girl child marriage in South Asia.

PMID- 22665098
TI  - Primary health care in low-income countries: building on recent achievements.

PMID- 22665099
TI  - Policy making with health equity at its heart.

PMID- 22665100
TI  - Achieving equity in global health: so near and yet so far.

PMID- 22665101
TI  - Noncommunicable diseases: a global health crisis in a new world order.

PMID- 22665102
TI  - A piece of my mind. A train of hope, and a chance to train.

PMID- 22665104
TI  - Effects of prenatal micronutrient and early food supplementation on maternal
      hemoglobin, birth weight, and infant mortality among children in Bangladesh: the
      MINIMat randomized trial.
AB  - CONTEXT: Nutritional insult in fetal life and small size at birth are common in
      low-income countries and are associated with serious health consequences.
      OBJECTIVES: To test the hypothesis that prenatal multiple micronutrient
      supplementation (MMS) and an early invitation to food supplementation would
      increase maternal hemoglobin level and birth weight and decrease infant
      mortality, and to assess whether a combination of these interventions would
      further enhance these outcomes. DESIGN, SETTING, AND PARTICIPANTS: A randomized
      trial with a factorial design in Matlab, Bangladesh, of 4436 pregnant women,
      recruited between November 11, 2001, and October 30, 2003, with follow-up until
      June 23, 2009. INTERVENTIONS: Participants were randomized into 6 groups; a
      double-masked supplementation with capsules of 30 mg of iron and 400 MUg of folic
      acid, 60 mg of iron and 400 MUg of folic acid, or MMS containing a daily
      allowance of 15 micronutrients, including 30 mg of iron and 400 MUg of folic
      acid, was combined with food supplementation (608 kcal 6 days per week)
      randomized to either early invitation (9 weeks' gestation) or usual invitation
      (20 weeks' gestation). MAIN OUTCOME MEASURES: Maternal hemoglobin level at 30
      weeks' gestation, birth weight, and infant mortality. Under 5-year mortality was
      also assessed. RESULTS: Adjusted maternal hemoglobin level at 30 weeks' gestation
      was 115.0 g/L (95% CI, 114.4-115.5 g/L), with no significant differences among
      micronutrient groups. Mean maternal hemoglobin level was lower in the early vs
      usual invitation groups (114.5 vs 115.4 g/L; difference, -0.9 g/L; 95% CI, -1.7
      to -0.1; P = .04). There were 3625 live births out of 4436 pregnancies. Mean
      birth weight among 3267 singletons was 2694 g (95% CI, 2680-2708 g), with no
      significant differences among groups. The early invitation with MMS group had an
      infant mortality rate of 16.8 per 1000 live births vs 44.1 per 1000 live births
      for usual invitation with 60 mg of iron and 400 MUg of folic acid (hazard ratio
      [HR], 0.38; 95% CI, 0.18-0.78). Early invitation with MMS group had an under 5
      year mortality rate of 18 per 1000 live births (54 per 1000 live births for usual
      invitation with 60 mg of iron and 400 MUg of folic acid; HR, 0.34; 95% CI, 0.18
      0.65). Usual invitation with MMS group had the highest incidence of spontaneous
      abortions and the highest infant mortality rate. CONCLUSION: Among pregnant women
      in poor communities in Bangladesh, treatment with multiple micronutrients,
      including iron and folic acid combined with early food supplementation, vs a
      standard program that included treatment with iron and folic acid and usual food
      supplementation, resulted in decreased childhood mortality. TRIAL REGISTRATION:
      isrctn.org Identifier: ISRCTN16581394.

PMID- 22665103
TI  - Effect of a multifaceted intervention on use of evidence-based therapies in
      patients with acute coronary syndromes in Brazil: the BRIDGE-ACS randomized
      trial.
AB  - CONTEXT: Studies have found that patients with acute coronary syndromes (ACS)
      often do not receive evidence-based therapies in community practice. This is
      particularly true in low- and middle-income countries. OBJECTIVE: To evaluate
      whether a multifaceted quality improvement (QI) intervention can improve the use
      of evidence-based therapies and reduce the incidence of major cardiovascular
      events among patients with ACS in a middle-income country. DESIGN, SETTING, AND
      PARTICIPANTS: The BRIDGE-ACS (Brazilian Intervention to Increase Evidence Usage
      in Acute Coronary Syndromes) trial, a cluster-randomized (concealed allocation)
      trial conducted among 34 clusters (public hospitals) in Brazil and enrolling a
      total of 1150 patients with ACS from March 15, 2011, through November 2, 2011,
      with follow-up through January 27, 2012. INTERVENTION: Multifaceted QI
      intervention including educational materials for clinicians, reminders,
      algorithms, and case manager training, vs routine practice (control). MAIN
      OUTCOME MEASURES: Primary end point was the percentage of eligible patients who
      received all evidence-based therapies (aspirin, clopidogrel, anticoagulants, and
      statins) during the first 24 hours in patients without contraindications.
      RESULTS: Mean age of the patients enrolled was 62 (SD, 13) years; 68.6% were men,
      and 40% presented with ST-segment elevation myocardial infarction, 35.6% with non
      ST-segment elevation myocardial infarction, and 23.6% with unstable angina. The
      randomized clusters included 79.5% teaching hospitals, all from major urban areas
      and 41.2% with 24-hour percutaneous coronary intervention capabilities. Among
      eligible patients (923/1150 [80.3%]), 67.9% in the intervention vs 49.5% in the
      control group received all eligible acute therapies (population average odds
      ratio [OR(PA)], 2.64 [95% CI, 1.28-5.45]). Similarly, among eligible patients
      (801/1150 [69.7%]), those in the intervention group were more likely to receive
      all eligible acute and discharge medications (50.9% vs 31.9%; OR(PA),, 2.49 [95%
      CI, 1.08-5.74]). Overall composite adherence scores were higher in the
      intervention clusters (89% vs 81.4%; mean difference, 8.6% [95% CI, 2.2%-15.0%]).
      In-hospital cardiovascular event rates were 5.5% in the intervention group vs
      7.0% in the control group (OR(PA), 0.72 [95% CI, 0.36-1.43]); 30-day all-cause
      mortality was 7.0% vs 8.4% (ORPA, 0.79 [95% CI, 0.46-1.34]). CONCLUSION: Among
      patients with ACS treated in Brazil, a multifaceted educational intervention
      resulted in significant improvement in the use of evidence-based therapies. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00958958.

PMID- 22665105
TI  - HIV development assistance and adult mortality in Africa.
AB  - CONTEXT: The effect of global health initiatives on population health is
      uncertain. Between 2003 and 2008, the US President's Emergency Plan for AIDS
      Relief (PEPFAR), the largest initiative ever devoted to a single disease,
      operated intensively in 12 African focus countries. The initiative's effect on
      all-cause adult mortality is unknown. OBJECTIVE: To determine whether PEPFAR was
      associated with relative changes in adult mortality in the countries and
      districts where it operated most intensively. DESIGN, SETTING, AND PARTICIPANTS:
      Using person-level data from the Demographic and Health Surveys, we conducted
      cross-country and within-country analyses of adult mortality (annual probability
      of death per 1000 adults between 15 and 59 years old) and PEPFAR's activities.
      Across countries, we compared adult mortality in 9 African focus countries
      (Ethiopia, Kenya, Mozambique, Namibia, Nigeria, Rwanda, Tanzania, Uganda, and
      Zambia) with 18 African nonfocus countries from 1998 to 2008. We performed
      subnational analyses using information on PEPFAR's programmatic intensity in
      Tanzania and Rwanda. We employed difference-in-difference analyses with fixed
      effects for countries and years as well as personal and time-varying area
      characteristics. MAIN OUTCOME MEASURE: Adult all-cause mortality. RESULTS: We
      analyzed information on 1 538 612 adults, including 60 303 deaths, from 41
      surveys in 27 countries, 9 of them focus countries. In 2003, age-adjusted adult
      mortality was 8.3 per 1000 adults in the focus countries (95% CI, 8.0-8.6) and
      8.5 per 1000 adults (95% CI, 8.3-8.7) in the nonfocus countries. In 2008,
      mortality was 4.1 per 1000 (95% CI, 3.6-4.6) in the focus countries and 6.9 per
      1000 (95% CI, 6.3-7.5) in the nonfocus countries. The adjusted odds ratio of
      mortality among adults living in focus countries compared with nonfocus countries
      between 2004 and 2008 was 0.84 (95% CI, 0.72-0.99; P = .03). Within Tanzania and
      Rwanda, the adjusted odds ratio of mortality for adults living in districts where
      PEPFAR operated more intensively was 0.83 (95% CI, 0.72-0.97; P = .02) and 0.75
      (95% CI, 0.56-0.99; P = .04), respectively, compared with districts where it
      operated less intensively. CONCLUSIONS: Between 2004 and 2008, all-cause adult
      mortality declined more in PEPFAR focus countries relative to nonfocus countries.
      It was not possible to determine whether PEPFAR was associated with mortality
      effects separate from reductions in HIV-specific deaths.

PMID- 22665107
TI  - Prevalence of malaria and sexually transmitted and reproductive tract infections
      in pregnancy in sub-Saharan Africa: a systematic review.
AB  - CONTEXT: Malaria and sexually transmitted infections/reproductive tract
      infections (STIs/RTIs) in pregnancy are direct and indirect causes of stillbirth,
      prematurity, low birth weight, and maternal and neonatal morbidity and mortality.
      OBJECTIVE: To conduct a systematic review and meta-analysis of malaria and
      STI/RTI prevalence estimates among pregnant women attending antenatal care
      facilities in sub-Saharan Africa. DATA SOURCES: PubMed, MEDLINE, EMBASE, the
      World Health Organization International Clinical Trials Registry, and reference
      lists were searched for studies reporting malaria, syphilis, Neisseria
      gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, or bacterial vaginosis
      among pregnant women attending antenatal care facilities in sub-Saharan Africa.
      STUDY SELECTION: Included studies were conducted in 1990-2011 with open
      enrollment. Studies from South Africa, where malaria is no longer endemic, were
      excluded. DATA EXTRACTION: Point prevalence estimates were corrected for
      diagnostic precision. A random-effects model meta-analysis was applied to produce
      pooled prevalence estimates. RESULTS: A total of 171 studies met inclusion
      criteria, providing 307 point prevalence estimates for malaria or STIs/RTIs and
      including a total of 340 904 women. The pooled prevalence estimates (with 95% CIs
      and number of women with positive diagnosis) among studies in 1990-2011 in East
      and Southern Africa were as follows: syphilis, 4.5% (3.9%-5.1%; n = 8346 positive
      diagnoses), N gonorrhoeae, 3.7% (2.8%-4.6%; n = 626), C trachomatis, 6.9% (5.1%
      8.6%; n = 350), T vaginalis, 29.1% (20.9%-37.2%; n = 5502), bacterial vaginosis,
      50.8% (43.3%-58.4%; n = 4280), peripheral malaria, 32.0% (25.9%-38.0%; n = 11
      688), and placental malaria, 25.8% (19.7%-31.9%; n = 1388). West and Central
      Africa prevalence estimates were as follows: syphilis, 3.5% (1.8%-5.2%; n = 851),
      N gonorrhoeae, 2.7% (1.7%-3.7%; n = 73), C trachomatis, 6.1% (4.0%-8.3%; n =
      357), T vaginalis, 17.8% (12.4%-23.1%; n = 822), bacterial vaginosis, 37.6%
      (18.0%-57.2%; n = 1208), peripheral malaria, 38.2% (32.3%-44.1%; n = 12 242), and
      placental malaria, 39.9% (34.2%-45.7%; n = 4658). CONCLUSION: The dual prevalence
      of malaria and STIs/RTIs in pregnancy among women who attend antenatal care
      facilities in sub-Saharan Africa is considerable, with the combined prevalence of
      curable STIs/RTIs being equal to, if not greater than, malaria.

PMID- 22665108
TI  - A framework convention on global health: health for all, justice for all.
AB  - Health inequalities represent perhaps the most consequential global health
      challenge and yet they persist despite increased funding and innovative programs.
      The United Nations is revising the Millennium Development Goals (MDGs) that will
      shape the world for many years to come. What would a transformative post-MDG
      framework for global health justice look like? A global coalition of civil
      society and academics--the Joint Action and Learning Initiative on National and
      Global Responsibilities for Health (JALI)--has formed an international campaign
      to advocate for a Framework Convention on Global Health (FCGH). Recently endorsed
      by the UN Secretary-General, the FCGH would reimagine global governance for
      health, offering a new post-MDG vision. This Special Communication describes the
      key modalities of an FCGH to illustrate how it would improve health and reduce
      inequalities. The modalities would include defining national responsibilities for
      the population's health; defining international responsibilities for reliable,
      sustainable funding; setting global health priorities; coordinating fragmented
      activities; reshaping global governance for health; and providing strong global
      health leadership through the World Health Organization.

PMID- 22665106
TI  - Association between changes in air pollution levels during the Beijing Olympics
      and biomarkers of inflammation and thrombosis in healthy young adults.
AB  - CONTEXT: Air pollution is a risk factor for cardiovascular diseases (CVD), but
      the underlying biological mechanisms are not well understood. OBJECTIVE: To
      determine whether markers related to CVD pathophysiological pathways (biomarkers
      for systemic inflammation and thrombosis, heart rate, and blood pressure) are
      sensitive to changes in air pollution. DESIGN, SETTING, AND PARTICIPANTS: Using a
      quasi-experimental opportunity offered by greatly restricted air pollution
      emissions during the Beijing Olympics, we measured pollutants daily and the
      outcomes listed below in 125 healthy young adults before, during, and after the
      2008 Olympics (June 2-October 30). We used linear mixed-effects models to
      estimate the improvement in outcome levels during the Olympics and the
      anticipated reversal of outcome levels after pollution controls ended to
      determine whether changes in outcome levels were associated with changes in
      pollutant concentrations. MAIN OUTCOME MEASURES: C-reactive protein (CRP),
      fibrinogen, von Willebrand factor, soluble CD40 ligand (sCD40L), soluble P
      selectin (sCD62P) concentrations; white blood cell count (WBC); heart rate; and
      blood pressure. RESULTS: Concentrations of particulate and gaseous pollutants
      decreased substantially (-13% to -60%) from the pre-Olympic period to the during
      Olympic period. Using 2-sided tests conducted at the .003 level, we observed
      statistically significant improvements in sCD62P levels by -34.0% (95% CI, -38.4%
      to -29.2%; P < .001) from a pre-Olympic mean of 6.29 ng/mL to a during-Olympic
      mean of 4.16 ng/mL and von Willebrand factor by -13.1% (95% CI, -18.6% to -7.5%;
      P < .001) from 106.4% to 92.6%. After adjustments for multiple comparisons,
      changes in the other outcomes were not statistically significant. In the post
      Olympic period when pollutant concentrations increased, most outcomes
      approximated pre-Olympic levels, but only sCD62P and systolic blood pressure were
      significantly worsened from the during-Olympic period. The fraction of above
      detection-limit values for CRP (percentage >= 0.3 mg/L) was reduced from 55% in
      the pre-Olympic period to 46% in the during-Olympic period and reduced further to
      36% in the post-Olympic period. Interquartile range increases in pollutant
      concentrations were consistently associated with statistically significant
      increases in fibrinogen, von Willebrand factor, heart rate, sCD62P, and sCD40L
      concentrations. CONCLUSIONS: Changes in air pollution levels during the Beijing
      Olympics were associated with acute changes in biomarkers of inflammation and
      thrombosis and measures of cardiovascular physiology in healthy young persons.
      These findings are of uncertain clinical significance.

PMID- 22665109
TI  - The question of improvement.

PMID- 22665110
TI  - Food, micronutrients, and birth outcomes.

PMID- 22665111
TI  - PEPFAR and maximizing the effects of global health assistance.

PMID- 22665112
TI  - China's air quality dilemma: reconciling economic growth with environmental
      protection.

PMID- 22665113
TI  - Health, economics, and the 2012 G8 Summit.

PMID- 22665118
TI  - JAMA patient page. Neonatal hyperbilirubinemia.

PMID- 22665119
TI  - Ganging up on angiotensin II type 1 receptors in vascular remodeling.

PMID- 22665120
TI  - A novel role for epidermal growth factor receptor tyrosine kinase and its
      downstream endoplasmic reticulum stress in cardiac damage and microvascular
      dysfunction in type 1 diabetes mellitus.
AB  - Epidermal growth factor receptor tyrosine kinase (EGFRtk) and endoplasmic
      reticulum (ER) stress are important factors in cardiovascular complications.
      Understanding whether enhanced EGFRtk activity and ER stress induction are
      involved in cardiac damage, and microvascular dysfunction in type 1 diabetes
      mellitus is an important question that has remained unanswered. Cardiac fibrosis
      and microvascular function were determined in C57BL/6J mice injected with
      streptozotocin only or in combination with EGFRtk inhibitor (AG1478), ER stress
      inhibitor (Tudca), or insulin for 2 weeks. In diabetic mice, we observed an
      increase in EGFRtk phosphorylation and ER stress marker expression (CHOP, ATF4,
      ATF6, and phosphorylated-eIF2alpha) in heart and mesenteric resistance arteries,
      which were reduced with AG1478, Tudca, and insulin. Cardiac fibrosis, enhanced
      collagen type I, and plasminogen activator inhibitor 1 were decreased with
      AG1478, Tudca, and insulin treatments. The impaired endothelium-dependent
      relaxation and -independent relaxation responses were also restored after
      treatments. The inhibition of NO synthesis reduced endothelium-dependent
      relaxation in control and treated streptozotocin mice, whereas the inhibition of
      NADPH oxidase improved endothelium-dependent relaxation only in streptozotocin
      mice. Moreover, in mesenteric resistance arteries, the mRNA levels of Nox2 and
      Nox4 and the NADPH oxidase activity were augmented in streptozotocin mice and
      reduced with treatments. This study unveiled novel roles for enhanced EGFRtk
      phosphorylation and its downstream ER stress in cardiac fibrosis and
      microvascular endothelial dysfunction in type 1 diabetes mellitus.

PMID- 22665121
TI  - Arterial properties as determinants of time-varying myocardial stress in humans.
AB  - Myocardial and arterial load are time-varying phenomena. Despite their importance
      in myocardial function, the arterial properties that determine time-resolved
      myocardial wall stress are unknown. We aimed to assess arterial properties as
      determinants of time-resolved myocardial stress among 1214 men and women enrolled
      in the Asklepios Study. Time-resolved central pressure, flow, and left
      ventricular geometry were measured with carotid tonometry, Doppler, and speckle
      tracking echocardiography, respectively, for computation of arterial load and
      ejection-phase time-varying myocardial wall stress. For any given end-diastolic
      left ventricular geometry and cardiac output, peak myocardial stress correlated
      directly with systemic vascular resistance (standardized beta=1.12; P<0.0001) and
      aortic characteristic impedance (standardized beta=0.17; P<0.0001). The ejection
      phase stress-time integral correlated with systemic vascular resistance
      (standardized beta=1.06; P<0.0001), lower total arterial compliance (standardized
      beta=-0.13; P=0.0008), and earlier return of wave reflections (standardized beta=
      0.10; P<0.0001) but not with reflection magnitude, whereas end-systolic wall
      stress correlated with systemic vascular resistance (standardized beta=1.06;
      P<0.0001) and reflection magnitude (standardized beta=0.12; P<0.0001). After
      adjustment for age, all of the measured arterial properties, end-diastolic left
      ventricular geometry, and cardiac output, women demonstrated greater peak (534
      versus 507 kdyne/cm(2); P<0.0001), end-systolic (335 versus 320 kdyne/cm(2);
      P<0.0001), and ejection-phase stress-time integral (157 versus 142 kdyne . s .
      cm(-2); P<0.0001). In conclusion, different arterial properties have selective
      effects on time-resolved ejection-phase myocardial wall stress, which are not
      apparent from single-time point measurements. Women demonstrate less efficient
      myocardial-arterial coupling, with higher wall stress development for any given
      left ventricular geometry, arterial properties, and flow output. These
      observations may relate to the differential susceptibility of women to heart
      failure.

PMID- 22665122
TI  - Knockdown of cytochrome P450 2E1 inhibits oxidative stress and apoptosis in the
      cTnT(R141W) dilated cardiomyopathy transgenic mice.
AB  - Cytochrome P450 2E1 (CYP2E1) is a cytochrome P450 enzyme that catalyzes the
      metabolism of toxic substrates. CYP2E1 is upregulated in heart disease, including
      the dilated cardiomyopathy (DCM) mouse model. Here, knockdown of CYP2E1
      significantly ameliorated the dilated left ventricle, thin wall, and
      dysfunctional contraction in the cTnT(R141W) and adriamycin-induced DCM mouse
      models. Interstitial fibrosis, poorly organized myofibrils, and swollen
      mitochondria with loss of cristae were improved in the myocardium of alpha-myosin
      heavy chain (MHC)-cTnT(R141W)*CYP2E1-silence double-transgenic mice when compared
      with the cTnT(R141W) transgenic mice. Oxidative stress, the activation of caspase
      3 and caspase 9, the release of cytochrome c, and the apoptosis in the myocardium
      were significantly decreased in double-transgenic mice compared with the
      cTnT(R141W) transgenic mice. In summary, the expression of CYP2E1 is upregulated
      in heart disease and might be induced by hypoxemia in cardiomyopathy. The
      overexpression of CYP2E1 can enhance the metabolism of endogenous ketones to meet
      the energy demand of the heart in certain disease states, but the overexpression
      of CYP2E1 can also increase oxidative stress and apoptosis in the DCM heart.
      Knockdown or downregulation of CYP2E1 might be a therapeutic strategy to control
      the development of DCM after mutations of cTnT(R141W) or other factors, because
      DCM is the third most common cause of heart failure and the most frequent cause
      of heart transplantation.

PMID- 22665123
TI  - Chronic hypoxia suppresses pregnancy-induced upregulation of large-conductance
      Ca2+-activated K+ channel activity in uterine arteries.
AB  - Our previous study demonstrated that increased Ca(2+)-activated K(+) (BK(Ca))
      channel activity played a key role in the normal adaptation of reduced myogenic
      tone of uterine arteries in pregnancy. The present study tested the hypothesis
      that chronic hypoxia during gestation inhibits pregnancy-induced upregulation of
      BK(Ca) channel function in uterine arteries. Resistance-sized uterine arteries
      were isolated from nonpregnant and near-term pregnant sheep maintained at sea
      level (~ 300 m) or exposed to high-altitude (3801 m) hypoxia for 110 days.
      Hypoxia during gestation significantly inhibited pregnancy-induced upregulation
      of BK(Ca) channel activity and suppressed BK(Ca) channel current density in
      pregnant uterine arteries. This was mediated by a selective downregulation of
      BK(Ca) channel beta1 subunit in the uterine arteries. In accordance, hypoxia
      abrogated the role of the BK(Ca) channel in regulating pressure-induced myogenic
      tone of uterine arteries that was significantly elevated in pregnant animals
      acclimatized to chronic hypoxia. In addition, hypoxia abolished the steroid
      hormone-mediated increase in the beta1 subunit and BK(Ca) channel current density
      observed in nonpregnant uterine arteries. Although the activation of protein
      kinase C inhibited BK(Ca) channel current density in pregnant uterine arteries of
      normoxic sheep, this effect was ablated in the hypoxic animals. The results
      demonstrate that selectively targeting BK(Ca) channel beta1 subunit plays a
      critical role in the maladaption of uteroplacental circulation caused by chronic
      hypoxia, which contributes to the increased incidence of preeclampsia and fetal
      intrauterine growth restriction associated with gestational hypoxia.

PMID- 22665124
TI  - Diets containing pistachios reduce systolic blood pressure and peripheral
      vascular responses to stress in adults with dyslipidemia.
AB  - Nut consumption reduces cardiovascular risk, and reductions in blood pressure and
      peripheral vascular resistance may be important mediators of this relationship.
      We evaluated effects of pistachios on flow-mediated dilation and blood pressure
      response to acute stress. Twenty-eight adults with dyslipidemia completed a
      randomized, crossover, controlled-feeding study. All of the meals were provided
      and calories were controlled. After 2 weeks on a typical Western diet (35% total
      fat and 11% saturated fat), test diets were presented in counterbalanced order
      for 4 weeks each, a low-fat control diet (25% total fat and 8% saturated fat), a
      diet containing 10% of energy from pistachios (on average, 1 serving per day; 30%
      total fat and 8% saturated fat), and a diet containing 20% of energy from
      pistachios (on average, 2 servings per day, 34% total fat and 8% saturated fat).
      None of the resting hemodynamic measures significantly differed from pretreatment
      values. When resting and stress levels were included in the repeated-measures
      analysis, average reductions in systolic blood pressure were greater after the
      diet containing 1 serving per day versus 2 servings per day of pistachios (mean
      change in systolic blood pressure, -4.8 vs -2.4 mm Hg, respectively; P<0.05).
      After the higher dose, there were significant reductions in peripheral resistance
      (-62.1 dyne . s * cm(-5)) and heart rate (-3 bpm) versus the control diet
      (P<0.0001). These changes were partially offset by increases in cardiac output.
      There was no effect of diet on fasting flow-mediated dilation. Reductions in
      peripheral vascular constriction and the resulting decrease in hemodynamic load
      may be important contributors to lower risk in nut consumers.

PMID- 22665125
TI  - Ischemic emergency?: endothelial cells have their own "adrenaline shot" at hand.

PMID- 22665126
TI  - Possible involvement of angiotensin-converting enzyme 2 and Mas activation in
      inhibitory effects of angiotensin II Type 1 receptor blockade on vascular
      remodeling.
AB  - We explored the roles of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1
      7), and Mas activation in angiotensin II type 1 receptor blockade-mediated
      attenuation of vascular remodeling. Vascular injury was induced by polyethylene
      cuff placement around the mouse femoral artery. After cuff placement, the mRNA
      level of both ACE2 and Mas was markedly decreased in wild-type mice, whereas ACE
      mRNA was not changed. Immunostaining of ACE2 and Mas was observed mainly in the
      media and was reduced in the injured artery. Administration of angiotensin-(1-7)
      decreased neointimal formation after cuff placement, whereas administration of [D
      Ala(7)] angiotensin-(1-7), a Mas antagonist, increased it. Consistent with these
      results, we also demonstrated that neointimal formation induced by cuff placement
      was further increased in ACE2 knockout mice. In angiotensin II type 1a receptor
      knockout mice, mRNA expression and immunostaining of ACE2 and Mas in the injured
      artery were greater, with less neointimal formation than in wild-type mice.
      Increased ACE2 expression in the injured artery was also observed by treatment of
      wild-type mice with an angiotensin II type 1 receptor blocker, olmesartan. These
      results suggested that activation of the ACE2-angiotensin-(1-7)-Mas axis is at
      least partly involved in the beneficial effects of angiotensin II type 1 receptor
      blockade on vascular remodeling.

PMID- 22665127
TI  - Myocardial wall stress: from hypertension to heart tension.

PMID- 22665128
TI  - Antioxidants and endothelial dysfunction in young and elderly people: is flow
      mediated dilation useful to assess acute effects?

PMID- 22665129
TI  - The epidermal growth factor receptor: a missing link between endoplasmic
      reticulum stress and diabetic complications?

PMID- 22665130
TI  - Endothelial cells are able to synthesize and release catecholamines both in vitro
      and in vivo.
AB  - Recently it has been demonstrated that catecholamines are produced and used by
      macrophages and mediate immune response. The aim of this study is to verify
      whether endothelial cells (ECs), which are of myeloid origin, can produce
      catecholamines. We demonstrated that genes coding for tyrosine hydroxylase, Dopa
      decarboxylase, dopamine beta hydroxylase (DbetaH), and phenylethanolamine-N
      methyl transferase, enzymes involved in the synthesis of catecholamines, are all
      expressed in basal conditions in bovine aorta ECs, and their expression is
      enhanced in response to hypoxia. Moreover, hypoxia enhances catecholamine
      release. To evaluate the signal transduction pathway that regulates catecholamine
      synthesis in ECs, we overexpressed in bovine aorta ECs either protein kinase A
      (PKA) or the transcription factor cAMP response element binding, because PKA/cAMP
      response element binding activation induces tyrosine hydroxylase transcription
      and activity in response to stress. Both cAMP response element binding and PKA
      overexpression enhance DbetaH and phenylethanolamine-N-methyl transferase gene
      expression and catecholamine release, whereas H89, inhibitor of PKA, exerts the
      opposite effect, evidencing the role of PKA/cAMP response element binding
      transduction pathway in the regulation of catecholamine release in bovine aorta
      ECs. We then evaluated by immunohistochemistry the expression of tyrosine
      hydroxylase, Dopa decarboxylase, DbetaH, and phenylethanolamine-N-methyl
      transferase in femoral arteries from hindlimbs of C57Bl/6 mice 3 days after
      removal of the common femoral artery to induce chronic ischemia. Ischemia evokes
      tyrosine hydroxylase, Dopa decarboxylase, DbetaH, and phenylethanolamine-N-methyl
      transferase expression in the endothelium. Finally, the pharmacological
      inhibition of catecholamine release by fusaric acid, an inhibitor of DbetaH,
      reduces the ability of ECs to form network-like structures on Matrigel matrix. In
      conclusion, our study demonstrates for the first time that ECs are able to
      synthesize and release catecholamines in response to ischemia.

PMID- 22665131
TI  - A randomized controlled pilot study comparing aqueous cream with a beeswax and
      herbal oil cream in the provision of relief from postburn pruritus.
AB  - Postburn itch is reported to affect up to 87% of the burn population. Although
      treatments for postburn itch are multimodal, they remain consistently
      ineffective. However, recent anecdotal evidence from several outpatients at a
      tertiary referral hospital suggests that a cream combining beeswax and several
      herbal oils may be effective in the minimization of postburn itch. The aim of
      this study was to test the efficacy of beeswax and herbal oil cream against the
      standard treatment of aqueous cream in the provision of relief from the symptoms
      of postburn itch. A randomized controlled trial compared two groups using a
      visual analog scale, frequency of cream application, itch recurrence after cream
      application, use of antipruritic medications, and sleep disturbance to determine
      the effect of itch severity and duration. Fifty-two participants were enrolled in
      the study (84% male) with a mean age of 35 years (SD = 16) and mean burn TBSA of
      7.2% (SD = 7.7). Study results found that the beeswax and herbal oil cream reduce
      itch after application more frequently than aqueous cream (P = .001). In
      addition, when managed with beeswax and herbal oil cream, participants found that
      their itch recurred later (P <= .001) and their use of antipruritic medications
      was lower (P = .023). Findings of this study suggest beeswax and herbal oil cream
      to be more effective in the minimization of postburn itch than aqueous cream.
      Given this, a larger study examining the efficacy of beeswax and herbal oil cream
      appears warranted.

PMID- 22665132
TI  - Complications of chlorine inhalation in a pediatric chemical burn patient:  a
      case report.
AB  - The majority of burn injuries in the pediatric population occur at home, and a
      significant proportion are the result of exposure to household cleaning products.
      A common injury-causing agent is bleach, which has the potential to release
      chlorine gas, a potent respiratory irritant that leads to the added risk of
      inhalation injury. The survival of pediatric patients with chemical burns is
      extremely high, and the 3 strongest predictors of mortality are large burn size,
      age <48 months, and the presence of inhalation injury. The authors present a rare
      case of a pediatric fatality from a chemical bleach burn that resulted in acute
      respiratory distress syndrome as well as hemodynamic and pulmonary instability
      that required extracorporeal membrane oxygenation. The authors critically
      appraised the management of this patient to determine the possible effect certain
      events had on the unexpected and poor outcome of this patient, including fluid
      resuscitation, the effect of the chemical inhalation injury, sedation, and the
      need for invasive extracorporeal membrane oxygenation life support.

PMID- 22665133
TI  - Phototoxicity in an ultraviolet ink manufacturing plant.
AB  - Ultraviolet (UV) dyes are used as inks in garment printing. Hypersensitivity
      reactions to these compounds have been reported in the literature. The authors
      report a case of reaction to UV ink in a patient already on corticosteroid
      therapy. The patient's clinical course was reviewed along with images of wounds
      that subsequently developed. The affected areas were debrided and covered with
      Vaseline gauze and silver impregnated dressings. Epithelium was salvaged in many
      areas, and regrowth occurred over several weeks in regions of deeper injury. The
      concurrent use of steroids and the rapidity of the onset of symptoms were not
      characteristic of hypersensitivity dermatitis, which has previously been
      reported. The cause of the wounds was likely phototoxicity from radical subtypes
      in the ink that catalyze the reaction when exposed to UV light.

PMID- 22665134
TI  - [Cancer pain in palliative medicine].
AB  - During the course of cancer progression up to 90% of the patients suffer from
      pain of nociceptive, neuropathic or mixed nociceptive/neuropathic origin.
      Psychological, social or existential factors may additionally affect the
      intensity of pain (concept of "total pain"). The WHO "analgesic ladder" provides
      a large variety of effective drugs that can be used according to the specific
      pain type. Parenteral or peridural opioid therapy as well as neurodestructive
      methods can effectively support the analgesic treatment in selected cases.

PMID- 22665135
TI  - Generation and characterization of bioluminescent xenograft mouse models of MLL
      related acute leukemias and in vivo evaluation of luciferase-targeting siRNA
      nanoparticles.
AB  - Chromosomal translocations involving the MLL gene on 11q23 present frequent
      abnormalities in pediatric, adult and therapy-related acute leukemias, and are
      generally associated with aggressive disease and poor prognosis. Here, we report
      bioluminescent acute leukemia xenograft mouse models of the most frequent and
      aggressive MLL-related acute leukemias (infant and adult MLL-AF9, MLL-ENL, MLL
      AF4). Four acute leukemia cell lines carrying MLL-related translocations were
      stably transduced with a firefly luciferase transgene and injected intravenously
      into NOD/SCID mice. Leukemia progression was monitored by in vivo bioluminescence
      imaging (BLI). All mice developed MLL-related acute leukemia. The four MLL
      related acute leukemia models showed a different course of infant and adult MLL
      AF9 acute myeloid leukemia, and a rapid aggressiveness of MLL-ENL acute
      lymphoblastic leukemia and MLL-AF4 acute biphenotypic leukemia. Tissue analysis
      and RT-PCR of bone marrow, spleen and liver from the mice confirmed the BL
      results. To validate BLI for the detection of a therapeutic response, systemic
      treatment with an anti-luciferase-targeting siRNA (siLuc) complexed with cationic
      nanoparticles was administered to mice with MLL-AF4 acute lymphoblastic leukemia.
      The BLI signal showed a reduction following treatment with siLuc compared to the
      control mice. These mouse models present MLL-related acute leukemia evolution
      similar to the human counterparts. Moreover, they are non-invasive, rapid and
      sensitive models, suitable for the in vivo study of MLL-related acute leukemias.
      Finally, BLI showed in vivo luminescence down modulation obtained by systemic
      treatment with luciferase-targeting siRNA nanoparticle complexes, confirming that
      these MLL-related leukemia mouse models are optimal for the evaluation and
      selection of delivery systems for siRNA and other new biotechnological
      pharmaceuticals.

PMID- 22665136
TI  - Dietary factors associated with overweight and body adiposity in Finnish children
      aged 6-8 years: the PANIC Study.
AB  - OBJECTIVES: To investigate the associations of dietary factors with overweight,
      body fat percentage (BF%), waist circumference (WC) and hip circumference (HC)
      among children. DESIGN: Cross-sectional analysis of the Physical Activity and
      Nutrition in Children (PANIC) Study among 510 children (263 boys, 247 girls) aged
      6-8 years from Kuopio, Finland. METHODS: The children's weight, height, WC and HC
      were measured. Overweight was defined by International Obesity Task Force body
      mass index cutoffs. The BF% was measured by dual-energy X-ray absorptiometry,
      nutrient intakes and meal frequency by 4-day food records and eating behaviour by
      Children's Eating Behaviour Questionnaire. RESULTS: Daily consumption of all the
      three main meals was inversely associated with overweight (odds ratio (OR) 0.37,
      95% confidence interval (CI) 0.18-0.75), BF% (beta -0.12, P = 0.012), WC (beta 
      0.16, P = 0.002) and HC (beta -0.15, P = 0.002). Enjoyment of food, food
      responsiveness and emotional overeating were directly associated with overweight
      (OR 1.57, 95% CI 1.04-2.35; OR 4.68, 95% CI 2.90-7.54; OR 2.60, 95% CI 1.52-4.45,
      respectively), BF% (beta 0.13, P = 0.004; beta 0.30, P<0.001; beta 0.09, P =
      0.035, respectively), WC (beta 0.14, P = 0.003; beta 0.40, P<0.001; beta 0.19,
      P<0.001, respectively) and HC (beta 0.15, P = 0.001; beta 0.38, P<0.001; beta
      0.15, P = 0.001, respectively). Satiety responsiveness was inversely associated
      with overweight (OR 0.42, 95% CI 0.26-0.67), BF% (beta -0.20, P<0.001), WC (beta 
      0.26, P<0.001) and HC (beta -0.26, P<0.001). Slowness in eating was inversely
      associated with overweight (OR 0.61, 95% CI 0.41-0.92), WC (beta -0.16, P =
      0.001) and HC (beta -0.17, P<0.001). Protein intake was directly associated with
      BF% (beta 0.11, P = 0.017), WC (beta 0.11, P = 0.020) and HC (beta 0.13, P =
      0.008). CONCLUSIONS: Promoting regular consumption of main meals and healthy
      eating behaviours should be emphasized in the prevention of overweight among
      children. More research is needed on the association of protein-rich foods with
      body adiposity in children.

PMID- 22665137
TI  - Liraglutide improves hippocampal synaptic plasticity associated with increased
      expression of Mash1 in ob/ob mice.
AB  - OBJECTIVE: Consumption of high-fat diet exerts adverse effects on learning and
      memory formation, which is linked to impaired hippocampal function. Activation of
      glucagon-like peptide-1 (GLP-1) signalling ameliorates detrimental effects of
      obesity-diabetes on cognitive function; however, mechanisms underlying these
      beneficial actions remain unclear. This study examined effects of daily
      subcutaneous treatment with GLP-1 mimetic, Liraglutide, on synaptic plasticity,
      hippocampal gene expression and metabolic control in adult obese diabetic (ob/ob)
      mice. RESULTS: Long-term potentiation (LTP) induced by area CA1 was completely
      abolished in ob/ob mice compared with lean controls. Deleterious effects on LTP
      were rescued (P<0.001) with Liraglutide. Indeed, Liraglutide-treated mice
      exhibited superior LTP profile compared with lean controls (P<0.01). Expression
      of hippocampal brain-derived neurotropic factor and neurotrophic tyrosine kinase
      receptor-type 2 were not significantly different, but synaptophysin and Mash1
      were decreased in ob/ob mice. Treatment with Liraglutide over 21 days increased
      expression of Mash1 in ob/ob mice (2.0-fold; P<0.01). These changes were
      associated with significantly reduced plasma glucose (21% reduction; P<0.05) and
      markedly improved plasma insulin concentrations (2.1- to 3.3-fold; P<0.05 to
      P<0.01). Liraglutide also significantly reduced the glycaemic excursion following
      an intraperitonal glucose load (area under curve (AUC) values: 22%; P<0.05) and
      markedly enhanced the insulin response to glucose (AUC values: 1.6-fold; P<0.05).
      O2 consumption, CO2 production, respiratory exchange ratio and energy expenditure
      were not altered by Liraglutide therapy. On day 21, accumulated food intake (32%
      reduction; P<0.05) and number of feeding bouts (32% reduction; P<0.05) were
      significantly reduced but simple energy restriction was not responsible for the
      beneficial actions of Liraglutide. CONCLUSION: Liraglutide elicits beneficial
      effects on metabolic control and synaptic plasticity in mice with severe obesity
      and insulin resistance mediated in part through increased expression of Mash1
      believed to improve hippocampal neurogenesis and cell survival.

PMID- 22665139
TI  - Identification of germline genomic copy number variation in familial pancreatic
      cancer.
AB  - Adenocarcinoma of the pancreas is a significant cause of cancer mortality, and up
      to 10 % of cases appear to be familial. Heritable genomic copy number variants
      (CNVs) can modulate gene expression and predispose to disease. Here, we identify
      candidate predisposition genes for familial pancreatic cancer (FPC) by analyzing
      germline losses or gains present in one or more high-risk patients and absent in
      a large control group. A total of 120 FPC cases and 1,194 controls were genotyped
      on the Affymetrix 500K array, and 36 cases and 2,357 controls were genotyped on
      the Affymetrix 6.0 array. Detection of CNVs was performed by multiple
      computational algorithms and partially validated by quantitative PCR. We found no
      significant difference in the germline CNV profiles of cases and controls. A
      total of 93 non-redundant FPC-specific CNVs (53 losses and 40 gains) were
      identified in 50 cases, each CNV present in a single individual. FPC-specific
      CNVs overlapped the coding region of 88 RefSeq genes. Several of these genes have
      been reported to be differentially expressed and/or affected by copy number
      alterations in pancreatic adenocarcinoma. Further investigation in high-risk
      subjects may elucidate the role of one or more of these genes in genetic
      predisposition to pancreatic cancer.

PMID- 22665140
TI  - Anaplastic glioma.
AB  - OPINION STATEMENT: The treatment of anaplastic glioma (AG) varies depending on
      histopathology of the tumor, molecular markers, and individual patient
      characteristics. Maximal surgical resection is desirable for all types of AG if
      technically feasible, with an acceptable level of risk, and with the goal of
      preserving neurologic function. As opposed to the standard treatment of
      glioblastoma, based on a large, randomized, phase 3 trial, there is no accepted
      standard treatment for AG. Anaplastic astrocytoma (AA) is most often treated with
      radiotherapy (RT), with or without concomitant temozolomide (TMZ) and with or
      without adjuvant temozolomide. Rarely is AA treated with chemotherapy alone,
      although different treatment modalities are being evaluated in ongoing trials.
      The treatment of anaplastic oligodendroglioma (AO) and anaplastic
      oligoastrocytoma (AOA) is influenced by the 1p/19q status, as allelic co-deletion
      of chromosomes 1p and 19q predicts increased sensitivity to chemotherapy and
      prolonged survival. In contrast to the treatment of AA, carefully selected
      patients with AO and AOA may be treated with chemotherapy alone. Temozolomide has
      largely replaced PCV (procarbazine, CCNU, vincristine) as the chemotherapeutic
      agent for AO and AOA, largely due to greater tolerability and less potential for
      toxicity. However, whether temozolomide has similar efficacy to PCV has not been
      fully evaluated. Patients with AO and AOA with significant residual tumor after
      surgery, intractable seizures, and/or non co-deleted 1p/19q status are often
      treated with RT with or without concomitant chemotherapy and with or without
      adjuvant chemotherapy. There is no standard postoperative care for anaplastic
      ependymoma (AE). The efficacy of upfront versus delayed RT has not been
      evaluated. Surgery may be indicated for patients with recurrent AG. There may be
      benefit on overall survival, although this has not been clearly proven.
      Reoperation may also provide symptomatic relief and confirm the pathology,
      including differentiation of radiation necrosis from recurrent tumor.
      Confirmation of tumor grade is often important for enrollment in clinical trials,
      a reasonable treatment choice for patients with recurrent tumor. Treatment of
      recurrent AG often depends on prior treatments. Patients who have progressed
      after RT alone may be treated with temozolomide or PCV. Patients treated
      previously with chemotherapy alone may be treated with RT at time of progression.
      Dose-intense temozolomide, bevacizumab alone, or bevacizumab in combination with
      a cytotoxic agent are other treatment options. Focused radiation such as
      stereotactic radiosurgery has no proven role in treating recurrent AG. A number
      of other treatment modalities are currently under active investigation, including
      targeted molecular inhibitors, immunotherapies, convection enhanced delivery, and
      viral gene therapies. There is no standard treatment for recurrent AE. Most
      patients undergo re-resection followed by RT if RT was not previously given.
      Chemotherapy may be given, but there is no standard chemotherapeutic regimen.
      Ongoing trials are evaluating the role of bevicizumab and targeted molecular
      agents in the treatment of AE.

PMID- 22665138
TI  - Large scale international replication and meta-analysis study confirms
      association of the 15q14 locus with myopia. The CREAM consortium.
AB  - Myopia is a complex genetic disorder and a common cause of visual impairment
      among working age adults. Genome-wide association studies have identified
      susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of
      European ancestry. Here, we present a confirmation and meta-analysis study in
      which we assessed whether these two loci are also associated with myopia in other
      populations. The study population comprised 31 cohorts from the Consortium of
      Refractive Error and Myopia (CREAM) representing 4 different continents with
      55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta
      analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on
      15q25 using linear regression analysis with spherical equivalent as a
      quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR)
      of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed
      effects meta-analysis. At locus 15q14, all SNPs were significantly replicated,
      with the lowest P value 3.87 * 10(-12) for SNP rs634990 in Caucasians, and 9.65 *
      10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 *
      10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88
      (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the
      top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous
      carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 * 10(
      2) for top SNP rs939661). We conclude that common variants at chromosome 15q14
      influence susceptibility for myopia in Caucasian and Asian populations world
      wide.

PMID- 22665141
TI  - Variants in the HEPSIN gene are associated with susceptibility to prostate
      cancer.
AB  - BACKGROUND: HEPSIN (HPN) gene is one of the most consistently overexpressed genes
      in patients with prostate cancer; furthermore, there is some evidence supporting
      an association between HPN gene variants and the risk of developing prostate
      cancer. In this study, sequence variants in the HPN gene were investigated to
      determine whether they were associated with prostate cancer risk in a Korean
      study cohort. METHODS: We evaluated the association of 17 single-nucleotide
      polymorphisms (SNPs) in the HPN gene with prostate cancer risk and clinical
      characteristics (Gleason score and tumor stage) in Korean men (240 case subjects
      and 223 control subjects) using unconditional logistic regression. RESULTS: The
      statistical analysis suggested that three SNPs (rs45512696, rs2305745, rs2305747)
      were significantly associated with the risk of prostate cancer (odds ratio
      (OR)=2.22, P=0.04; OR=0.73, P=0.03; OR=0.76, P=0.05, respectively). CONCLUSIONS:
      The results of this study suggest that, in Korean men, some polymorphisms in the
      HPN gene might be associated with the risk of developing prostate cancer.

PMID- 22665142
TI  - Measuring cell cycle progression kinetics with metabolic labeling and flow
      cytometry.
AB  - Precise control of the initiation and subsequent progression through the various
      phases of the cell cycle are of paramount importance in proliferating cells. Cell
      cycle division is an integral part of growth and reproduction and deregulation of
      key cell cycle components have been implicated in the precipitating events of
      carcinogenesis. Molecular agents in anti-cancer therapies frequently target
      biological pathways responsible for the regulation and coordination of cell cycle
      division. Although cell cycle kinetics tend to vary according to cell type, the
      distribution of cells amongst the four stages of the cell cycle is rather
      consistent within a particular cell line due to the consistent pattern of mitogen
      and growth factor expression. Genotoxic events and other cellular stressors can
      result in a temporary block of cell cycle progression, resulting in arrest or a
      temporary pause in a particular cell cycle phase to allow for instigation of the
      appropriate response mechanism. The ability to experimentally observe the
      behavior of a cell population with reference to their cell cycle progression
      stage is an important advance in cell biology. Common procedures such as mitotic
      shake off, differential centrifugation or flow cytometry-based sorting are used
      to isolate cells at specific stages of the cell cycle. These fractionated, cell
      cycle phase-enriched populations are then subjected to experimental treatments.
      Yield, purity and viability of the separated fractions can often be compromised
      using these physical separation methods. As well, the time lapse between
      separation of the cell populations and the start of experimental treatment,
      whereby the fractionated cells can progress from the selected cell cycle stage,
      can pose significant challenges in the successful implementation and
      interpretation of these experiments. Other approaches to study cell cycle stages
      include the use of chemicals to synchronize cells. Treatment of cells with
      chemical inhibitors of key metabolic processes for each cell cycle stage are
      useful in blocking the progression of the cell cycle to the next stage. For
      example, the ribonucleotide reductase inhibitor hydroxyurea halts cells at the
      G1/S juncture by limiting the supply of deoxynucleotides, the building blocks of
      DNA. Other notable chemicals include treatment with aphidicolin, a polymerase
      alpha inhibitor for G1 arrest, treatment with colchicine and nocodazole, both of
      which interfere with mitotic spindle formation to halt cells in M phase and
      finally, treatment with the DNA chain terminator 5-fluorodeoxyridine to initiate
      S phase arrest. Treatment with these chemicals is an effective means of
      synchronizing an entire population of cells at a particular phase. With removal
      of the chemical, cells rejoin the cell cycle in unison. Treatment of the test
      agent following release from the cell cycle blocking chemical ensures that the
      drug response elicited is from a uniform, cell cycle stage-specific population.
      However, since many of the chemical synchronizers are known genotoxic compounds,
      teasing apart the participation of various response pathways (to the
      synchronizers vs. the test agents) is challenging. Here we describe a metabolic
      labeling method for following a subpopulation of actively cycling cells through
      their progression from the DNA replication phase, through to the division and
      separation of their daughter cells. Coupled with flow cytometry quantification,
      this protocol enables for measurement of kinetic progression of the cell cycle in
      the absence of either mechanically- or chemically- induced cellular stresses
      commonly associated with other cell cycle synchronization methodologies. In the
      following sections we will discuss the methodology, as well as some of its
      applications in biomedical research.

PMID- 22665143
TI  - Intestinal colonisation and blood stream infections due to vancomycin-resistant
      enterococci (VRE) and extended-spectrum beta-lactamase-producing
      Enterobacteriaceae (ESBLE) in patients with haematological and oncological
      malignancies.
AB  - BACKGROUND: In patients with haematological or oncological malignancies, we aimed
      to assess the rate of intestinal colonisation and blood stream infections (BSI)
      with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) and
      vancomycin-resistant enterococci (VRE), mortality and risk factors associated
      with ESBLE/VRE BSI, as well as the impact of faecal screening for ESBLE and VRE
      in combination with adapted empiric treatment of febrile neutropenia. METHODS:
      Within 72 h of admission to our department, an ESBLE and VRE screening stool
      sample was collected. In the case of neutropenic fever, blood cultures were
      drawn. Data of all admitted patients were prospectively documented. Explorative
      forward-stepwise logistic regression analyses were used to identify risk factors
      for progression from intestinal colonisation to BSI. RESULTS: During the study
      period, 1,805 stool samples were obtained from 513 patients during 1,012
      inpatient stays, and 2,766 blood cultures were obtained from 578 patients during
      1,091 inpatient stays. Ninety (17.5 %) of these patients were colonised with
      ESBLE and 51 (9.9 %) with VRE. Proportions of 40 % (36/90) of ESBLE and 61 %
      (31/51) of VRE colonisations were healthcare-associated. Six of 90 (6.6 %) ESBLE
      colonised patients and 1/51 (2 %) VRE-colonised patients developed BSI with the
      respective organism. None of these patients died after receiving early
      appropriate empiric antibiotics based on colonisation status. Colonisation with
      ESBLE or VRE was associated with increased risk ratios (RR) towards developing
      ESBLE BSI [RR 4.5, 95 % confidence interval (CI): 2.89-7.04] and VRE BSI (RR
      10.2, 95 % CI: 7.87-13.32), respectively. Acute myelogenous leukaemia and prior
      treatment with platinum analogues or quinolones were identified as independent
      risk factors for ESBLE BSI in colonised patients. CONCLUSIONS: Intestinal
      ESBLE/VRE colonisation predicts BSI. Faecal screening in haematology/oncology
      patients in combination with directed empiric treatment may reduce ESBLE BSI
      related mortality.

PMID- 22665145
TI  - Generalizability: the trees, the forest, and the low-hanging fruit.
AB  - Clinical and epidemiologic investigations are paying increasing attention to the
      critical constructs of "representativeness" of study samples and
      "generalizability" of study results. This is a laudable trend and yet, these key
      concepts are often misconstrued and conflated, masking the central issues of
      internal and external validity. The authors define these issues and demonstrate
      how they are related to one another and to generalizability. Providing examples,
      they identify threats to validity from different forms of bias and confounding.
      They also lay out relevant practical issues in study design, from sample
      selection to assessment of exposures, in both clinic-based and population-based
      settings.

PMID- 22665146
TI  - Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot
      clinical trial.

PMID- 22665144
TI  - Long-term soy isoflavone supplementation and cognition in women: a randomized,
      controlled trial.
AB  - OBJECTIVE: To determine the cognitive effects of long-term dietary soy
      isoflavones in a daily dose comparable to that of traditional Asian diets.
      METHODS: In the double-blind Women's Isoflavone Soy Health trial, healthy
      postmenopausal women were randomly allocated to receive daily 25 g of isoflavone
      rich soy protein (91 mg of aglycone weight of isoflavones: 52 mg of genistein, 36
      mg of daidzein, and 3 mg glycitein) or milk protein-matched placebo. The primary
      cognitive endpoint compared between groups at 2.5 years was change from baseline
      on global cognition, a composite of the weighted sum of 14 neuropsychological
      test score changes. Secondary outcomes compared changes in cognitive factors and
      individual tests. RESULTS: A total of 350 healthy postmenopausal women aged 45-92
      years enrolled in this trial; 313 women with baseline and endpoint cognitive test
      data were included in intention-to-treat analyses. Adherence in both groups was
      nearly 90%. There was no significant between-group difference on change from
      baseline in global cognition (mean standardized improvement of 0.42 in the
      isoflavone group and 0.31 in the placebo group; mean standardized difference
      0.11, 95% confidence interval [CI] -0.13 to 0.35). Secondary analyses indicated
      greater improvement on a visual memory factor in the isoflavone group (mean
      standardized difference 0.33, 95% CI 0.06-0.60) but no significant between-group
      differences on 3 other cognitive factors or individual test scores, and no
      significant difference within a subgroup of younger postmenopausal women.
      CONCLUSION: For healthy postmenopausal women, long-term dietary soy isoflavone
      supplementation in a dose comparable to that of traditional Asian diets has no
      effect on global cognition but may improve visual memory. CLASSIFICATION OF
      EVIDENCE: This study provides Class I evidence that long-term dietary
      supplementation with isoflavone-rich soy protein does not improve global
      cognition of healthy postmenopausal women.

PMID- 22665147
TI  - Ethics: end-of-life decision-making in a pediatric patient with SMA type 2: the
      influence of the media.
AB  - OBJECTIVE: Spinal muscular atrophy (SMA) is a group of progressive and fatal
      neurodegenerative disorders that are characterized by destruction of the anterior
      horn cells of the spinal cord. In this case report we outline the medical and
      ethical issues involved in a 7-year-old boy with SMA type 2 who experienced acute
      respiratory failure. METHODS: A review of the literature was conducted focusing
      particularly on the pathology, presentation, and outcomes of SMA and end-of-life
      decision-making in pediatrics. RESULTS: In a world where 40%-60% of deaths in
      pediatric intensive care units are a result of withdrawal or limitation of life
      sustaining treatment, end-of-life decision-making has become an integral and
      difficult part of pediatric practice. CONCLUSION: Limitation or withdrawal of
      life-sustaining treatment in a cognitively normal child with SMA poses a
      significant medical and ethical dilemma. This difficult decision is influenced by
      confluence of parental, doctor, social, cultural, moral, religious, legal, and
      economic factors and more recently the media.

PMID- 22665148
TI  - Teaching neuroimages: ictal hyperperfusion.

PMID- 22665149
TI  - Advance directives to physicians:  what every physician should know.

PMID- 22665150
TI  - Commentary on "advance directives to physicians:  what every physician should
      know".

PMID- 22665151
TI  - Explaining and improving breast cancer information acquisition among African
      American women in the Deep South.
AB  - OBJECTIVES: A major challenge facing contemporary cancer educators is how to
      optimize the dissemination of breast cancer prevention and control information to
      African American women in the Deep South who are believed to be cancer free. The
      purpose of this research was to provide insight into the breast cancer
      information-acquisition experiences of African American women in Alabama and
      Mississippi and to make recommendations on ways to better reach members of this
      high-risk, underserved population. METHODS: Focus group methodology was used in a
      repeated, cross-sectional research design with 64 African American women, 35
      years old or older who lived in one of four urban or rural counties in Alabama
      and Mississippi. RESULTS: Axial-coded themes emerged around sources of cancer
      information, patterns of information acquisition, characteristics of preferred
      sources, and characteristics of least-preferred sources. CONCLUSIONS: It is
      important to invest in lay health educators to optimize the dissemination of
      breast cancer information to African American women who are believed to be cancer
      free in the Deep South.

PMID- 22665152
TI  - Misclassification of pulmonary hypertension in adults with sickle
      hemoglobinopathies using Doppler echocardiography.
AB  - OBJECTIVE: To compare the diagnostic utility of Doppler echocardiography-derived
      tricuspid regurgitant jet velocity (TRV) >= 2.5 m/s to right heart
      catheterization (RHC) in defining pulmonary hypertension (PH) in adult patients
      with sickle cell disease (SCD). METHODS: This is a retrospective chart review of
      adults with SCD who had a TRV >= 2.5 m/s and RHC. A TRV >= 2.5 m/s is suggestive
      of PH. Pulmonary arterial hypertension (PAH) was defined as a mean pulmonary
      artery pressure (mPAP) >= 25 mm Hg and pulmonary capillary wedge pressure <= 15
      mm Hg. Pulmonary venous hypertension was defined as an mPAP >= 25 mm Hg and
      pulmonary capillary wedge pressure >15 mm Hg. RESULTS: Twenty-five patients with
      SCD met the inclusion criteria. Nine of the 25 (36%) patients had an mPAP >= 25
      mm Hg. Of these 9, 3 (33%) had PAH and 6 (66%) had pulmonary venous hypertension.
      Patients with PH did not have a higher TRV (3.1 +/- 0.68 vs 2.70 +/- 0.16 m/s; P
      = 0.12), but they did have higher cardiac outputs (10.4 +/- 2.7 vs 7.81 +/- 1.85
      L/min; P = 0.012. The specificity of TRV equal to 2.51 m/s in diagnosing PH was
      18.8%. At a TRV of 2.88 m/s, the specificity increased to 81%. CONCLUSIONS: In
      adults with SCD, a TRV of 2.5 m/s lacks specificity for use as a screening tool
      in the diagnosis of PH. Using a TRV of >= 2.88 m/s allows the TRV to be used as a
      screening tool and reduces the false-positive rate and need for unnecessary RHC.

PMID- 22665153
TI  - Relation between prefracture characteristics and perioperative complications in
      the elderly adult patient with hip fracture.
AB  - BACKGROUND: The exact relation among patient prefracture characteristics such as
      age, American Society of Anesthesiologists (ASA) class, fracture type, and
      prefracture mobility status with perioperative complications in elderly adult
      patients with hip fracture is still unclear. The aim of the study was to assess
      the relations among patient prefracture characteristics and perioperative
      complications. METHODS: Patients 65 years old and older admitted to our
      institution between January 2006 and May 2010 with the diagnosis of a low-energy
      hip fracture were retrospectively reviewed. A total of 389 patients met the
      inclusion criteria and were analyzed in this investigation. Patient prefracture
      characteristics, comorbidities, and surgical and hospital courses were reviewed.
      RESULTS: Using logistic regression analysis, ASA class was found to be the only
      significant predictor of a patient having at least one or more perioperative
      complications (odds ratio [OR] 2.007). In addition to ASA class, prefracture
      mobility status was a significant predictor of delirium (OR 1.39) and pneumonia
      (OR 1.77), advanced age was a significant predictor of congestive heart failure
      (OR 1.73), and fracture type was a significant predictor of pneumonia (OR 1.6).
      None of the examined prefracture characteristics was found to be a significant
      predictor of pulmonary embolus, deep venous thrombosis, surgical wounds,
      transfusions, urinary tract infection, or death. CONCLUSIONS: At our institution,
      certain patient prefracture characteristics, particularly high ASA class, are
      related to certain perioperative complications. Recognition of patients who
      possess these risk factors can be used to alert the caregiving team about a
      potentially complicated hospital course.

PMID- 22665154
TI  - Commentary on "relation between prefracture characteristics and perioperative
      complications in the elderly adult patient with hip fracture".

PMID- 22665155
TI  - Epidemiology of the reported severity of copperhead (Agkistrodon contortrix)
      snakebite.
AB  - OBJECTIVE: The goal of this study was to analyze trends in the annual rates of
      reported medical outcomes of US copperhead (Agkistrodon contortrix) snakebites
      published in the annual reports of the American Association of Poison Control
      Centers in the course of 26 years. METHODS: This was a retrospective analysis of
      medical outcomes for copperhead snakebite victims who developed fatal, major,
      moderate, minor, or no effects. The annual rates for these medical outcomes were
      calculated by dividing the annual number of patients in each outcome category by
      the total annual number of people reported as being bitten by copperheads.
      Poisson and negative binomial regression were used to examine trends in annual
      rates. RESULTS: From 1983 through 2008, the incidence rate of copperhead
      snakebites causing no effect significantly decreased by 12.1%/year (incidence
      rate ratio [IRR] 0.879; 95% confidence interval [CI] 0.848-0.911]. From 1985
      through 2008, the incidence rate of minor outcomes significantly decreased by
      2.3%/year (IRR 0.977; 95% CI 0.972-0.981), whereas the rate of moderate outcomes
      significantly increased by 2.8%/year (IRR 1.028; 95% CI 1.024-1.033). The rate of
      major outcomes did not significantly change. One fatality was reported in 2001.
      CONCLUSIONS: Annual rates of copperhead snakebites producing no effects and minor
      outcomes significantly decreased, those producing moderate outcomes significantly
      increased, and those producing major outcomes did not significantly change in a
      26-year period.

PMID- 22665156
TI  - Commentary on "Epidemiology of the Reported Severity of Copperhead (Agkistrodon
      contortrix) Snakebite".

PMID- 22665157
TI  - Palindromic rheumatism:  strategies to prevent evolution to rheumatoid arthritis.

PMID- 22665158
TI  - Recurrence of Helicobacter pylori After Eradication in Patients with Peptic
      Ulcer.

PMID- 22665160
TI  - Sperm characteristics and androgens in Acipenser ruthenus after induction of
      spermiation by carp pituitary extract or GnRHa implants.
AB  - Spermiation and changes in androgen (testosterone, T and 11-ketotestosterone, 11
      KT) levels were studied in sterlet (Acipenser ruthenus) treated with GnRH agonist
      implants (DAla(6)-Pro(9)-LHRHa) at 25 and 75 MUg kg(-1) b.w. and compared with
      those males treated with 4 mg kg(-1) b.w. of carp pituitary extract (CPE) and 3
      pellets of Ovopel kg(-1) b.w., which contains DAla(6)-Pro(9)NEt-mGnRH and
      metoclopramide. Sperm quality (sperm mass, spermatozoa concentration and sperm
      motility and velocity) was evaluated 24, 48 and 72 h after hormonal treatments.
      Males did not release sperm in the control group injected with physiological
      solution, while sperm could not be collected 7 days after treatments in all
      hormonally treated groups. Spermiation rates were 100 % in the CPE and Ovopel
      groups and 25-50 % in the GnRHa-treated groups. Sperm production was
      significantly lower in the GnRHa-treated groups than in the CPE and Ovopel groups
      and decreased 72 h after hormonal treatment. Sperm motility and velocity were
      higher in the Ovopel and GnRHa (75 MUg) groups compared to the CPE and GnRHa (25
      MUg) groups and decreased 72 h after hormonal treatment. Androgens were only
      affected in spermiating males and changed in the Ovopel and GnRHa (75 MUg) after
      hormonal treatment. Significant correlations were observed between sperm
      production, sperm motility and sperm velocity, but not androgens. The present
      study suggests involvement of dopamine in sturgeon spawning. Additionally, better
      sperm quality observed in the Ovopel group and particularly sperm motility in the
      GnRHa (75 MUg) suggests enhancement of sperm quality in sturgeon treated with
      GnRHa. Therefore, further study is needed to induce fully spermiation using GnRHa
      implants in combination with a dopamine inhibitor.

PMID- 22665161
TI  - High throughput generated micro-aggregates of chondrocytes stimulate cartilage
      formation in vitro and in vivo.
AB  - Cell-based cartilage repair strategies such as matrix-induced autologous
      chondrocyte implantation (MACI) could be improved by enhancing cell performance.
      We hypothesised that micro-aggregates of chondrocytes generated in high
      throughput prior to implantation in a defect could stimulate cartilaginous matrix
      deposition and remodelling. To address this issue, we designed a micro-mould to
      enable controlled high-throughput formation of micro-aggregates. Morphology,
      stability, gene expression profiles and chondrogenic potential of micro
      aggregates of human and bovine chondrocytes were evaluated and compared to single
      cells cultured in micro-wells and in 3D after encapsulation in Dextran-Tyramine
      (Dex-TA) hydrogels in vitro and in vivo. We successfully formed micro-aggregates
      of human and bovine chondrocytes with highly controlled size, stability and
      viability within 24 hours. Micro-aggregates of 100 cells presented a superior
      balance in Collagen type I and Collagen type II gene expression over single cells
      and micro-aggregates of 50 and 200 cells. Matrix metalloproteinases 1, 9 and 13
      mRNA levels were decreased in micro-aggregates compared to single-cells.
      Histological and biochemical analysis demonstrated enhanced matrix deposition in
      constructs seeded with micro-aggregates cultured in vitro and in vivo, compared
      to single-cell seeded constructs. Whole genome microarray analysis and single
      gene expression profiles using human chondrocytes confirmed increased expression
      of cartilage-related genes when chondrocytes were cultured in micro-aggregates.
      In conclusion, we succeeded in controlled high-throughput formation of micro
      aggregates of chondrocytes. Compared to single cell-seeded constructs, seeding of
      constructs with micro-aggregates greatly improved neo-cartilage formation.
      Therefore, micro-aggregation prior to chondrocyte implantation in current MACI
      procedures, may effectively accelerate hyaline cartilage formation.

PMID- 22665163
TI  - Effect of fibrin on osteogenic differentiation and VEGF expression of bone marrow
      stromal cells in mineralised scaffolds: a three-dimensional analysis.
AB  - The aim of the present study was to test the hypothesis that a fibrin matrix
      enhances the osteogenic differentiation and expression of vascular endothelial
      growth factor (VEGF) by human bone marrow stromal cells (hBMSCs) seeded into
      mineralised scaffolds. Porous calcium carbonate scaffolds were droplet seeded
      with hBMSCs using a matrix containing 3 % fibrinogen and cultured for 3 weeks.
      Seeded scaffolds without the fibrin matrix served as controls. The scaffolds were
      evaluated, using undecalcified thick sections, for fluorescence staining for
      nuclei, osteocalcin (OC) and VEGF. The sections were systematically scanned using
      optical sectioning and three dimensional distributions of cells and positive
      staining indicating expression of OC and VEGF were reconstructed from the z
      stacks. The fibrin matrix maintained a significantly higher level of cell numbers
      after 2 d and 1 week and delayed the onset of osteogenic differentiation while
      sustaining a significantly higher level of OC and VEGF expression after 2 and 3
      weeks, starting from the periphery of the scaffolds. There was a decrease in cell
      density from the periphery to the centre of the scaffolds in both groups The
      percentage of cells expressing OC and VEGF was significantly different between
      the centre and the periphery of the scaffolds in the fibrin(+) group but not in
      the controls. It is concluded that the fibrin matrix used appears to be a useful
      adjunct for supporting and sustaining osteogenic and angiogenic activity of
      hBMSCs in tissue engineered constructs. This could help to improve their
      performance in a clinical setting.

PMID- 22665162
TI  - Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle
      cell infiltration in a hindlimb ischemia model.
AB  - Peripheral artery disease (PAD) currently affects approximately 27 million
      patients in Europe and North America, and if untreated, may progress to the stage
      of critical limb ischemia (CLI), which has implications for amputation and
      potential mortality. Unfortunately, few therapies exist for treating the ischemic
      skeletal muscle in these conditions. Biomaterials have been used to increase cell
      transplant survival as well as deliver growth factors to treat limb ischemia;
      however, existing materials do not mimic the native skeletal muscle
      microenvironment they are intended to treat. Furthermore, no therapies involving
      biomaterials alone have been examined. The goal of this study was to develop a
      clinically relevant injectable hydrogel derived from decellularized skeletal
      muscle extracellular matrix and examine its potential for treating PAD as a stand
      alone therapy by studying the material in a rat hindlimb ischemia model. We
      tested the mitogenic activity of the scaffold's degradation products using an in
      vitro assay and measured increased proliferation rates of smooth muscle cells and
      skeletal myoblasts compared to collagen. In a rat hindlimb ischemia model, the
      femoral artery was ligated and resected, followed by injection of 150 uL of
      skeletal muscle matrix or collagen 1 week post-injury. We demonstrate that the
      skeletal muscle matrix increased arteriole and capillary density, as well as
      recruited more desmin-positive and MyoD-positive cells compared to collagen. Our
      results indicate that this tissue-specific injectable hydrogel may be a potential
      therapy for treating ischemia related to PAD, as well as have potential
      beneficial effects on restoring muscle mass that is typically lost in CLI.

PMID- 22665164
TI  - Involvement of reactive oxygen species and glutathione in gallic acid-induced
      human umbilical vein endothelial cell death.
AB  - Gallic acid (GA) has various biological effects including apoptosis. In this
      study, we investigated the effects of GA on human primary umbilical vein
      endothelial cells (HUVECs) in relation to cell growth, cell death, reactive
      oxygen species (ROS) and glutathione (GSH). Treatment with 200 or 400 uM GA
      inhibited the growth of HUVECs at 24 h and induced cell death, which was
      accompanied by the loss of mitochondrial membrane potential (MMP; ?Psim). GA
      decreased or increased ROS levels including O2*-. It dose-dependently increased
      GSH depleted cell numbers. Pan-caspase inhibitor (Z-VAD) did not affect cell
      growth inhibition, cell death, ROS and GSH levels in GA-treated HUVECs. However,
      N-acetyl-cysteine (NAC; a well known antioxidant) and L-buthionine sulfoximine
      (BSO; an inhibitor of GSH synthesis) enhanced cell growth inhibition, cell death
      and MMP (?Psim) loss in GA-treated HUVECs. NAC decreased general ROS levels in GA
      treated HUVECs, but strongly increased O2*- levels in these cells. Both NAC and
      BSO intensified the GSH depletion of GA-treated HUVECs. In conclusion, GA
      treatment induced growth inhibition and death of HUVECs. The changes of ROS and
      GSH levels by NAC and BSO influenced cell growth and death in GA-treated HUVECs.

PMID- 22665165
TI  - Metabolomics reveals an essential role for peroxisome proliferator-activated
      receptor alpha in bile acid homeostasis.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear
      receptor that regulates fatty acid transport and metabolism. Previous studies
      revealed that PPARalpha can affect bile acid metabolism; however, the mechanism
      by which PPARalpha regulates bile acid homeostasis is not understood. In this
      study, an ultraperformance liquid chromatography coupled with electrospray
      ionization qua dru pole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS)-based
      metabolomics approach was used to profile metabolites in urine, serum, and bile
      of wild-type and Ppara-null mice following cholic acid (CA) dietary challenge.
      Metabolomic analysis showed that the levels of several serum bile acids, such as
      CA (25-fold) and taurocholic acid (16-fold), were significantly increased in CA
      treated Ppara-null mice compared with CA-treated wild-type mice. Phospholipid
      homeostasis, as revealed by decreased serum lysophos phati dylcholine (LPC) 16:0
      (1.6-fold) and LPC 18:0 (1.6-fold), and corticosterone metabolism noted by
      increased urinary excretion of 11beta-hydroxy-3,20-dioxopregn-4-en-21-oic acid
      (20-fold) and 11beta,20alpha-dihydroxy-3-oxo-pregn-4-en-21-oic acid (3.6-fold),
      were disrupted in CA-treated Ppara-null mice. The hepatic levels of mRNA encoding
      transporters Abcb11, Abcb4, Abca1, Abcg5, and Abcg8 were diminished in Ppara-null
      mice, leading to the accumulation of bile acids in the liver during the CA
      challenge. These observations revealed that PPARalpha is an essential regulator
      of bile acid biosynthesis, transport, and secretion.

PMID- 22665166
TI  - Cholesteryl ester acyl oxidation and remodeling in murine macrophages: formation
      of oxidized phosphatidylcholine.
AB  - Cholesterol is an essential component of eukaryotic cell membranes, regulating
      fluidity and permeability of the bilayer. Outside the membrane, cholesterol is
      esterified to fatty acids forming cholesterol esters (CEs). Metabolism of CEs is
      characterized by recurrent hydrolysis and esterification as part of the CE cycle;
      however, since recombinant 15-lipoxygenase (15-LO) was shown to oxidize
      cholesteryl linoleate of LDL, there has been interest in CE oxidation,
      particularly in the context atherogenesis. Studies of oxidized CE (oxCE)
      metabolism have focused on hydrolysis and subsequent reverse cholesterol
      transport with little emphasis on the fate the newly released oxidized fatty acyl
      component. Here, using mass spectrometry to analyze lipid oxidation products, CE
      metabolism in murine peritoneal macrophages was investigated. Ex vivo macrophage
      incubations revealed that cellular 15-LO directly oxidized multiple CE substrates
      from intracellular stores and from extracellular sources. Freshly harvested
      murine macrophages also contained 15-LO-specific oxCEs, suggesting the enzyme may
      act as a CE-oxidase in vivo. The metabolic fate of oxCEs, particularly the
      hydrolysis and remodeling of oxidized fatty acyl chains, was also examined in the
      macrophage. Metabolism of deuterated CE resulted in the genesis of deuterated,
      oxidized phosphatidylcholine (oxPC). Further experiments revealed these oxPC
      species were formed chiefly from the hydrolysis of oxidized CE and subsequent
      reacylation of the oxidized acyl components into PC.

PMID- 22665169
TI  - Enhanced resistance to blast (Magnaporthe grisea) in transgenic Japonica rice by
      constitutive expression of rice chitinase.
AB  - Rice blast is the most devastating plant disease in Japan. Our goal is to create
      new rice varieties which show enhanced resistance against blast, regardless of
      the race of blast. By an Agrobacterium-mediated transformation method, we
      reintroduced a rice class-I chitinase gene, Cht-2 or Cht-3, under the control of
      the enhanced CaMV 35S promoter and a hygromycin phosphotransferase gene, as a
      selection marker into the Japonica rice varieties Nipponbare and Koshihikari,
      which have retained the best popularity over a long period in Japan. In
      regenerated plants (R(0)), the Cht-2 product was found to accumulate
      intracellularly whereas the Cht-3 product was found to be targeted
      extracellularly. The transgenic rice plants which constitutively expressed either
      chitinase gene showed significantly higher resistance against the rice blast
      pathogen Magnaporthe grisea races 007.0 and 333. Both high-level expression of
      the chitinase and blast-resistance were stably inherited by the next generation
      in several lines.

PMID- 22665168
TI  - To UPR... and beyond! A new role for a BiP/GRP78 protein in the control of
      antimicrobial peptide expression in C. elegans epidermis.
AB  - The fungal pathogen Drechmeria coniospora infects C. elegans and elicits an
      innate immune response mediated, in part, by the induction of antimicrobial
      peptides in the epidermis. The signaling pathways controlling this phenomenon
      remain to be fully characterized. In this issue of Virulence, Couillault and
      colleagues use both proteomics and genetics to discover an unexpected role for
      the unfolded protein response (UPR) target chaperone BiP/GRP78/hsp-3 in the
      control of fungal infection-induced antimicrobial peptide expression in C.
      elegans. Although the expression of hsp-3 is regulated by the UPR, Couillault and
      colleagues describe a novel signaling role for this BiP/GRP78 homolog.

PMID- 22665170
TI  - Centromeric localization of an S-RNase gene in Petunia hybrida Vilm.
AB  - S-RNase has been identified to be an S-allele-specific stylar determinant
      contributing to the self-incompatibility response in Solanaceae. In order to
      examine the physical location of the S-RNase gene, multi-color fluorescence in
      situ hybridization (FISH) using the S (B1) -RNase cDNA probe and ribosomal RNA
      gene (rDNA) probe was performed on an S (B1) S (B2 )heterozygote of Petunia
      hybrida. The S (B1) -RNase gene was detected as a doublet signal close to the
      centromere of chromosome III. Next, we performed FISH using a large genome probe
      prepared from a lambdaSB1-311 clone (20 kb) which contains the S (B1) -RNase gene
      and its 3' flanking region. This probe hybridized to the centromeric regions of
      all P. hybrida chromosomes. Sequence analysis of the lambdaSB1-311 clone revealed
      the presence of a repetitive sequence consisting of a novel 666 bp unit sequence.
      A subclone (pBS-SB1B5) containing this unit sequence also hybridized to all of
      the centromeric regions, confirming that this unit is the centromeric specific
      repetitive sequence. These data suggested that the S ( B1 ) -RNase gene is
      located very close to (within a distance of 12 kb from) the centromeric-specific
      repetitive sequence. Likewise, the pBS-SB1B5 probe hybridized to the centromeric
      regions of all chromosomes in P. littoralis, another Petunia species. However,
      the probe did not hybridize to the centromere of the chromosomes from other
      species in Solanaceae. These results suggested that this centromeric repetitive
      sequence might be a genus-specific one.

PMID- 22665171
TI  - Isolation and partial characterization of a lead-accumulating Brassica juncea
      mutant.
AB  - A new screening method for non-destructive, high-sensitivity, high-throughput
      isolation of plant mutants capable of accumulating large amounts of heavy metals
      has been developed. This method is based on incubating seedlings in a solution
      containing radioisotopes of the metals of interest and visualizing the tissue
      accumulation of these metals with a phosphorimager. We used this technique to
      isolate mutants of Brassica juncea (L.) Czern with increased accumulation of Cd
      and Pb for use in phytoremediation, an emerging technology using plants to
      remediate polluted soil and water. Approximately 50,000 M2 seedlings were
      screened and 21 mutants were recovered that retained increased accumulation
      through the third generation. Mutant 7/15-1 is characterized by enhanced Pb
      accumulation per unit of root fresh weight, stunted root growth, and decreased
      root cell size. Data indicate that roots of 7/15-1 contain more cell-wall
      material on a fresh-weight basis than roots of the wild-type, which may at least
      partially explain its ability to accumulate more Pb.

PMID- 22665167
TI  - Modulation of oxidative stress, inflammation, and atherosclerosis by lipoprotein
      associated phospholipase A2.
AB  - Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), also known as platelet
      activating factor acetylhydrolase (PAF-AH), is a unique member of the
      phospholipase A(2) superfamily. This enzyme is characterized by its ability to
      specifically hydrolyze PAF as well as glycerophospholipids containing short,
      truncated, and/or oxidized fatty acyl groups at the sn-2 position of the glycerol
      backbone. In humans, Lp-PLA(2) circulates in active form as a complex with low-
      and high-density lipoproteins. Clinical studies have reported that plasma Lp
      PLA(2) activity and mass are strongly associated with atherogenic lipids and
      vascular risk. These observations led to the hypothesis that Lp-PLA(2) activity
      and/or mass levels could be used as biomarkers of cardiovascular disease and that
      inhibition of the activity could offer an attractive therapeutic strategy.
      Darapladib, a compound that inhibits Lp-PLA(2) activity, is anti-atherogenic in
      mice and other animals, and it decreases atherosclerotic plaque expansion in
      humans. However, disagreement continues to exist regarding the validity of Lp
      PLA(2) as an independent marker of atherosclerosis and a scientifically justified
      target for intervention. Circulating Lp-PLA(2) mass and activity are associated
      with vascular risk, but the strength of the association is reduced after
      adjustment for basal concentrations of the lipoprotein carriers with which the
      enzyme associates. Genetic studies in humans harboring an inactivating mutation
      at this locus indicate that loss of Lp-PLA(2) function is a risk factor for
      inflammatory and vascular conditions in Japanese cohorts. Consistently,
      overexpression of Lp-PLA(2) has anti-inflammatory and anti-atherogenic properties
      in animal models. This thematic review critically discusses results from
      laboratory and animal studies, analyzes genetic evidence, reviews clinical work
      demonstrating associations between Lp-PLA(2) and vascular disease, and summarizes
      results from animal and human clinical trials in which administration of
      darapladib was tested as a strategy for the management of atherosclerosis.

PMID- 22665172
TI  - Molecular diversity at the major cluster of disease resistance genes in
      cultivated and wild Lactuca spp.
AB  - Diversity was analyzed in wild and cultivated Lactuca germplasm using molecular
      markers derived from resistance genes of the NBS-LRR type. Three molecular
      markers, one microsatellite marker and two SCAR markers that amplified LRR
      encoding regions, were developed from sequences of resistance gene homologs at
      the main resistance gene cluster in lettuce. Variation for these markers were
      assessed in germplasm including accessions of cultivated lettuce, Lactuca sativa
      L. and three wild Lactuca spp., L. serriola L., L. saligna and L. virosa L.
      Diversity was also studied within and between natural populations of L. serriola
      from Israel and California; the former is close to the center of diversity for
      Lactuca spp. while the latter is an area of more recent colonization. Large
      numbers of haplotypes were detected indicating the presence of numerous
      resistance genes in wild species. The diversity in haplotypes provided evidence
      for gene duplication and unequal crossing-over during the evolution of this
      cluster of resistance genes. However, there was no evidence for duplications and
      deletions within the LRR-encoding regions studied. The three markers were highly
      correlated with resistance phenotypes in L. sativa. They were able to
      discriminate between accessions that had previously been shown to be resistant to
      all known isolates of Bremia lactucae. Therefore, these markers will be highly
      informative for the establishment of core collections and marker-aided selection.
      A hierarchical analysis of the population structure of L. serriola showed that
      countries, as well as locations, were significantly differentiated. These
      differences may reflect local founder effects and/or divergent selection.

PMID- 22665173
TI  - A bacterial artificial chromosome library for sugarcane.
AB  - Modern cultivated sugarcane is a complex aneuploid polyploid with an estimated
      genome size of 3000 Mb. Although most traits in sugarcane show complex
      inheritance, a rust locus showing monogenic inheritance has been documented. In
      order to facilitate cloning of the rust locus, we have constructed a bacterial
      artificial chromosome (BAC) library for the cultivar R570. The library contains
      103,296 clones providing 4.5 sugarcane genome equivalents. A random sampling of
      240 clones indicated an average insert size of 130 kb allowing a 98% probability
      of recovering any specific sequence of interest. High-density filters were
      gridded robotically using a Genetix Q-BOT in a 4 * 4 double-spotted array on 22.5
      cm(2) filters. Each set of five filters provides a genome coverage of 4x with
      18,432 clones represented per filter. Screening of the library with three
      different barley chloroplast gene probes indicated an exceptionally low
      chloroplast DNA content of less than 1%. To demonstrate the library's potential
      for map-based cloning, single-copy RFLP sugarcane mapping probes anchored to nine
      different linkage groups and three different gene probes were used to screen the
      library. The number of positive hybridization signals resulting from each probe
      ranged from 8 to 60. After determining addresses of the signals, clones were
      evaluated for insert size and HindIII-fingerprinted. The fingerprints were then
      used to determine clone relationships and assemble contigs. For comparison with
      other monocot genomes, sugarcane RFLP probes were also used to screen a Sorghum
      bicolor BAC library and two rice BAC libraries. The rice and sorghum BAC clones
      were characterized for insert size and fingerprinted, and the results compared to
      sugarcane. The library was screened with a rust resistance RFLP marker and
      candidate BAC clones were subjected to RFLP fragment matching to identify those
      corresponding to the same genomic region as the rust gene.

PMID- 22665174
TI  - AFLP markers in a molecular linkage map of maize: codominant scoring and linkage
      group ditsribution.
AB  - We exploited the AFLP technique to saturate a RFLP linkage map derived from a
      maize mapping population. By using two restriction enzyme, EcoRI and PstI,
      differing in methylation sensitivity, both in combination with MseI, we detected
      1568 bands of which 340 where polymorphic. These were added to the exitsing RFLP
      marker data to study the effects of incorporation of AFLPs produced by different
      restriction-enzyme combinations upon genetic maps. Addition of the AFLP data
      resulted in greater genome coverage, both through linking previously separate
      groups and the extension of other groups. The increase of the total map length
      was mainly caused by the addition of markers to telomeric regions, where RFLP
      markers were poorly represented. The percentage of informative loci was
      significantly different between the EcoRI and PstI assays. There was also
      evidence that PstI AFLP markers were more randomly distributed across chromosomes
      and chromosome regions, while EcoRI AFLP markers clustered mainly at centomeric
      regions. The more-random ditsribution of PstI AFLP markers on the genetic map
      reported here may reflect a preferential localisation of the markers in the
      hypomethylated telomeric regions of the chromosomes.

PMID- 22665175
TI  - Agronomic performance of lines derived from anther culture, maize pollination and
      single-seed descent in a spring wheat cross.
AB  - Anther culture and maize hybridization are two frequently used techniques for
      doubled haploid production in wheat (Triticum aestivum L.). Information on the
      field performance of lines derived from these techniques is limited. This study
      was conducted to compare the performance of F(4:6) lines obtained by single-seed
      descent with lines obtained by anther culture and maize (Zea mays L.) pollination
      from the same cross of spring wheat, 'Chris'/MN 7529. Thirty-three lines derived
      from each of those techniques were evaluated in six environments for grain yield,
      protein content, test weight, heading date, kernel weight and plant height. Mean
      performance of the single-seed descent lines exceeded performance of the anther
      culture lines for grain yield, kernel weight and plant height with no apparent
      differences for grain protein content, test weight and heading date. No
      differences between trait means for the single-seed descent and maize pollination
      lines were found except for plant height. The best 5 lines from each method for
      grain yield, protein content and test weight were similar in performance except
      that the protein content was higher for the maize pollination lines than for the
      single-seed descent lines. Acceptable levels of agronomic performance could be
      found among lines from each method. Wide acceptance of the doubled haploid
      technique for pure line production in breeding programs may, however, be limited
      by the often poor efficiency of doubled haploid line production, resulting in
      smaller population sizes for selection of desirable traits in comparison to the
      single-seed descent method.

PMID- 22665176
TI  - Production of transgenic tropical maize with cryIAb and cryIAc genes via
      microprojectile bombardment of immature embryos.
AB  - To enhance the level of resistance to insects in tropical maize germplasm we have
      developed techniques to successfully transform elite tropical maize inbred based
      on the activity of specific cryI proteins against four major maize pests - corn
      earworm, fall armyworm, southwestern corn borer and sugarcane borer. Constructs
      containing cryIAb or cryIAc synthetic genes were used. To generate transgenic
      plants we have established methods for biolistic bombardment and the selection
      and regeneration of immature embryos and calli from the elite tropical lines
      CML72, CML216, CML323, CML327 and hybrids. Transgenic plants resistant to the
      herbicide Basta(TM) contained the bands for the cry, bar and gus genes as
      detected by Southern blot analyses. A simple leaf bioassay presented varying
      levels of resistance to Southwestern corn borer of transgenic tropical maize
      carrying the cryIAc gene. Analyses of the progenies confirmed the sexual
      transmission of the introduced genes and their stable expression.

PMID- 22665177
TI  - A high-density molecular map for ryegrass (Lolium perenne)  using AFLP markers.
AB  - AFLP markers have been successfully employed for the development of a high
      density linkage map of ryegrass (Lolium perenne L.) using a progeny set of 95
      plants from a testcross involving a doubled-haploid tester. This genetic map
      covered 930 cM in seven linkage groups and was based on 463 amplified fragment
      length polymorphism (AFLP) markers using 17 primer pairs, three isozymes and five
      EST markers. The average density of markers was approximately 1 per 2.0 cM.
      However, strong clustering of AFLP markers was observed at putative centromeric
      regions. Around these regions, 272 markers covered about 137 cM whereas the
      remaining 199 markers covered approximately 793 cM. Most genetic distances
      between consecutive pairs of markers were smaller than 20 cM except for five gaps
      on groups A, C, D, F and G. A skeletal map with a uniform distribution of markers
      can be extracted from this high-density map, and can be applied to detect and map
      QTLs. We report here the application of AFLP markers to genome mapping, in Lolium
      as a prelude to quantitative trait locus (QTL) identification for diverse
      agronomic traits in ryegrass and for marker-assisted plant breeding.

PMID- 22665178
TI  - Development and utility of cleaved amplified polymorphic sequences (CAPS) and
      restriction fragment length polymorphisms (RFLPs) linked to the Fom-2 fusarium
      wilt resistance gene in melon (Cucumis melo L.).
AB  - Fusarium wilt, caused by Fusarium oxysporum Schlecht f. sp. melonis Snyder &
      Hans, is a worldwide soil-borne disease of melon (Cucumis melo L.). Resistance to
      races 0 and 1 of Fusarium wilt is conditioned by the dominant gene Fom-2. To
      facilitate marker-assisted backcrossing with selection for Fusarium wilt
      resistance, we developed cleaved amplified polymorphic sequences (CAPS) and
      restriction fragment length polymorphisms (RFLP) markers by converting RAPD
      markers E07 (a 1.25-kb band) and G17 (a 1.05-kb band), respectively. The RAPD-PCR
      polymorphic fragments from the susceptible line 'Vedrantais' were cloned and
      sequenced in order to construct primers that would amplify only the target
      fragment. The derived primers, E07SCAR-1/E07SCAR-2 from E07 and G17SCAR-1/G17SCAR
      2 from G17, yielded a single 1.25-kb fragment (designated SCE07) and a 1.05-kb
      fragment (designated SCG17) (the same as RAPD markers E07 and G17), respectively,
      from both resistant and susceptible melon lines, thus demonstrating locus
      specific associated primers. Potential CAPS markers were first revealed by
      comparing sequence data between fragments amplified from resistant (PI 161375)
      and susceptible ('Vedrantais') lines and were then confirmed by electrophoresis
      of restriction endonuclease digestion products. Twelve restriction endonucleases
      were evaluated for their potential use as CAPS markers within the SCE07 fragment.
      Three (BclI, MspI, and BssSI) yielded ideal CAPS markers and were subsequently
      subjected to extensive testing using an additional 88 diverse melon cultigens, 93
      and 119 F(2) individuals from crosses of 'Vedrantais' x PI 161375 and 'Ananas
      Yokneam'*MR-1 respectively, and 17 families from a backcross BC(1)S(1) population
      derived from the breeding line 'MD8654' as a resistance source. BclI- and MspI
      CAPS are susceptible-linked markers, whereas the BssSI-CAPS is a resistant-linked
      marker. The CAPS markers that resulted from double digestion by BclI and BssSI
      are co-dominant. Results from BclI- and MspI-CAPS showed over 90% accuracy in the
      melon cultigens, and nearly 100% accuracy in the F(2) individuals and BC(1)S(1)
      families tested. This is the first report of PCR-based CAPS markers linked to
      resistance/susceptibility for Fusarium wilt in melon. The RFLP markers resulting
      from probing with a clone-derived 1.05-kb SCG17 PCR fragment showed 85% correct
      matches to the disease phenotype. Both the CAPS and RFLP markers were co
      dominant, easier to score, and more accurate and consistent in predicting the
      melon phenotype than the RAPD markers from which they were derived.

PMID- 22665179
TI  - Low-Cot DNA sequences for fingerprinting analysis  of germplasm diversity and
      relationships in Amaranthus.
AB  - We examined genetic diversity and relationships among 24 cultivated and wild
      Amaranthus accessions using the total low-Cot DNA and five individual repetitive
      sequences as probes. These low-Cot DNA probes were obtained by the isolation of
      various classes of repetitive-DNA sequences, including satellites,
      minisatellites, microsatellites, rDNA, retrotransposon-like sequences, and other
      unidentified novel repetitive sequences. DNA fingerprints generated by different
      types of repetitive-DNA probes revealed different levels of polymorphism in the
      Amaranthus genomes. A repetitive sequence containing microsatellites was found to
      be a suitable probe for characterizing intraspecific accessions, whereas more
      conservative sequences (e.g. rDNA) were informative for resolving phylogenetic
      relationships among distantly related species.Genetic diversity, measured as
      restriction fragment length polymorphism (RFLP) and the similarity index at the
      low-Cot DNA level, was equally high among intraspecific accessions between the
      two species groups: grain amaranths (A. caudatus, A. cruentus, and A.
      hypochondriacus) and their putative wild progenitors (A. hybridus, A. powellii,
      and A. quitensis). At the interspecific level, however, the grain amaranth
      species are less divergent from each other than their wild progenitors. With the
      rare exceptions of certain A. caudatus accessions, grain amaranths were found to
      be closely related to A. hybridus. The results based on low-Cot DNA were
      comparable with previous RAPD and isozyme studies of the same set of
      species/accessions of Amaranthus, indicating that low-Cot DNA sequences are
      suitable probes for a fingerprinting analysis of plant germplasm diversity and
      for determining phylogenetic relationships.

PMID- 22665180
TI  - Relationships among maize inbred lines and populations from European and North
      American origins as estimated using RFLP markers.
AB  - RFLP markers have proven to be a reliable and highly informative tool for
      characterizing genetic diversity in maize. Joint analysis of inbred lines and
      populations should provide valuable information with respect to (1) a better
      understanding of the genetic basis of present elite germplasm and (2) the
      identification of populations that may prove to be useful sources of genetic
      diversity for breeding programs. Sixty-two inbred lines of known heterotic groups
      and ten maize populations, some of them significant contributors to the genetic
      basis of the heterotic groups, were assayed at 28 RFLP loci. Joint data analyses
      first underlined that the populations displayed a large number of alleles that
      were absent in the set of inbred lines. Associations among inbreds and
      populations further proved consistent with pedigree data of the inbreds and
      provided new information on the genetical basis of heterotic groups. In
      particular, European flint inbreds were revealed to be as close to the
      Northeastern U.S. flint population studied as to the typical European
      populations. These results advocate the analysis of larger sets of populations by
      means of molecular markers in order to (1) gain insight into the history of maize
      germplasm and (2) set up appropriate strategies for the use of genetic resources
      in breeding programs.

PMID- 22665181
TI  - Expanding informativeness of microsatellite motifs through the analysis of
      heteroduplexes: a case applied to Solanum tuberosum.
AB  - The incorporation of heteroduplex analysis into conventional strategies for the
      study of polymorphisms at microsatellite loci has allowed us to obtain
      information useful in determining genetic diversity and relationships among
      organisms. We have chosen, as a model for the testing of this strategy, several
      Solanum tuberosum varieties cultivated on Tenerife Island (Canary Archipelago)
      and a (TCT)(n) microsatellite located in intron I from the gene for granule-bound
      starch synthase. The data obtained confirm the high degree of agreement between
      molecular and farmer taxonomy.

PMID- 22665182
TI  - Single-stranded DNA in the genetic transformation of wheat (Triticum aestivum
      L.): transformation frequency and integration pattern.
AB  - Two non-linked marker genes (gus and bar) were co-introduced by microprojectile
      bombardment into wheat cells. Four different DNA structures were compared with
      respect to ability to integrate into the wheat genome: circular or linear (l) DNA
      as a single- or double-stranded plasmid (ss and ds, respectively). In eight
      independent experiments, linearized DNA integrated in the ds or ss form with a
      high efficiency of up to 14% for l-ssDNA. Molecular analyses by Southern blotting
      showed that all DNA forms gave a similar complicated integration pattern of the
      bar gene.

PMID- 22665183
TI  - Spectrum of resistance to root-knot nematodes and inheritance of heat-stable
      resistance in in pepper (Capsicum annuum L.).
AB  - Capsicum annuum L. has resistance to root-knot nematodes (RKN) (Meloidogyne
      spp.), severe polyphagous pests that occur world-wide. Several single dominant
      genes confer this resistance. Some are highly specific, whereas others are
      effective against a wide range of species. The spectrum of resistance to eight
      clonal RKN populations of the major Meloidogyne species, M. arenaria (2
      populations), M. incognita (2 populations), M. javanica (1 population), and M.
      hapla (3 populations) was studied using eight lines of Capsicum annuum. Host
      susceptibility was determined by counting the egg masses (EM) on the roots.
      Plants were classified into resistant (R; EM <= 5) or susceptible (H; EM >5)
      classes. The french cultivar Doux Long des Landes was susceptible to all
      nematodes tested. The other seven pepper lines were highly resistant to M.
      arenaria, M. javanica and one population of M. hapla. Variability in resistance
      was observed for the other two populations of M. hapla. Only lines PM687, PM217,
      Criollo de Morelos 334 and Yolo NR were resistant to M. incognita. To investigate
      the genetic basis of resistance in the highly resistant line PM687, the
      resistance of two progenies was tested with the two populations of M. incognita:
      118 doubled-haploid (DH) lines obtained by androgenesis from F(1) hybrids of the
      cross between PM687 and the susceptible cultivar Yolo Wonder, and 163 F(2)
      progenies. For both nematodes populations, the segregation patterns 69 R / 49 S
      for DH lines and 163 R / 45 S for F(2) progenies were obtained at 22 degrees C
      and at high temperatures (32 degrees C and 42 degrees C). The presence of a
      single dominant gene that totally prevented multiplication of M. incognita was
      thus confirmed and its stability at high temperature was demonstrated. This study
      confirmed the value of C. annuum  as a source of complete spectrum resistance to
      the major RKN.

PMID- 22665184
TI  - Citrus and Prunuscopia-like retrotransposons.
AB  - Many of the world's most important citrus cultivars ("Washington Navel",
      satsumas, clementines) have arisen through somatic mutation. This phenomenon
      occurs fairly often in the various species and varieties of the genus.The
      presence of copia-like retrotransposons has been investigated in fruit trees,
      especially citrus, by using a PCR assay designed to detect copia-like reverse
      transcriptase (RT) sequences. Amplification products from a genotype of each the
      following species Citrus sinensis, Citrus grandis, Citrus clementina, Prunus
      armeniaca and Prunus amygdalus, were cloned and some of them sequenced. Southern
      blot hybridization using RT clones as probes showed that multiple copies are
      integrated throughout the citrus genome, while only 1-3 copies are detected in
      the P. armeniaca genome, which is in accordance with the Citrus and Prunus genome
      sizes. Sequence analysis of RT clones allowed a search for homologous sequences
      within three gene banks. The most similar ones correspond to RT domains of copia
      like retrotransposons from unrelated plant species. Cluster analysis of these
      sequences has shown a great heterogeneity among RT domains cloned from the same
      genotype. This finding supports the hypothesis that horizontal transmission of
      retrotransposons has occurred in the past. The species presenting a RT sequence
      most similar to citrus RT clones is Gnetum montanum, a gymnosperm whose
      distribution area coincides with two of the main centers of origin of Citrus spp.
      A new C-methylated restriction DNA fragment containing a RT sequence is present
      in navel sweet oranges, but not in Valencia oranges from which the former
      originated suggesting, that retrotransposon activity might be, at least in part,
      involved in the genetic variability among sweet orange cultivars. Given that
      retrotransposons are quite abundant throughout the citrus genome, their activity
      should be investigated thoroughly before commercializing any transgenic citrus
      plant where the transgene(s) is part of a viral genome in order to avoid its
      possible recombination with an active retroelement. Focusing on other strategies
      to control virus diseases is recommended in citrus.

PMID- 22665185
TI  - Genetic analysis of apomixis in Citrus and Poncirus by molecular markers.
AB  - Propagation of citrus rootstocks depends upon the production of clonal plants
      from nucellar seedlings. This makes apomixis one of the host important traits in
      breeding programs for citrus rootstocks. The genetic control of apomixis was
      studied in a 50-tree progeny derived from the cross C. volkameriana*P. trifoliata
      using 69 molecular markers and bulked segregant analysis. The proportion of
      nucellar seedlings was estimated by isoenzymatic analysis of 25 seedlings per
      tree for 2 consecutive years. The type of embryony (polyembryonic versus
      monoembryonic seeds) was also determined for fruit-yielding trees. Separate
      genetic maps for each parental species were developed. The integration and
      comparison of these maps could be accomplished using common multiallelic
      segregant loci. Differences in gene synteny between the two species-specific
      genetic maps were shown. Important distortions in the segregation of markers at
      several genomic regions, some of them also involving differences in the C
      methylation pattern, have been observed, especially for the pollen parent.
      Analysis of quantitative trait loci (QTLs) revealed the presence of six genomic
      positions (two in P. trifoliata and four in C. volkameriana) contributing
      individually up to 24% of the total variation for apomixis. Within the same
      species, QTLs with positive and negative allele effects were present, even in the
      same linkage group. One of the markers associated to apomixis (Apo2) is also
      associated to embryony type. Therefore, the genetic control of apomictic
      reproduction found in citrus (nucellar embryony) is quite complex compared to
      what has been reported for gametophytic apomixis. Molecular markers linked to
      QTLs governing apomixis will be useful to assist selection of future apomictic
      rootstocks for citrus varieties.

PMID- 22665186
TI  - Mapping of QTL for downy mildew resistance in maize.
AB  - Quantitative trait loci (QTLs) of maize involved in mediating resistance to
      Peronosclerospora sorghi, the causative agent of sorghum downy mildew (SDM), were
      detected in a population of recombinant inbred lines (RILs) derived from the Zea
      mays L. cross between resistant (G62) and susceptible (G58) inbred lines. Field
      tests of 94 RILs were conducted over two growing seasons using artificial
      inoculation. Heritability of the disease reaction was high (around 70%). The
      mapping population of the RILs was also scored for restriction fragment length
      polymorphic (RFLP) markers. One hundred and six polymorphic RFLP markers were
      assigned to ten chromosomes covering 1648 cM. Three QTLs were detected that
      significantly affected resistance to SDM combined across seasons. Two of these
      mapped quite close together on chromosome 1, while the third one was on
      chromosome 9. The percentage of phenotypic variance explained by each QTL ranged
      from 12.4% to 23.8%. Collectively, the three QTLs identified in this study
      explained 53.6% of the phenotypic variation in susceptibility to the infection.
      The three resistant QTLs appeared to have additive effects. Increased
      susceptibility was contributed by the alleles of the susceptible parent. The
      detection of more than one QTL supports the hypothesis that several qualitative
      and quantitative genes control resistance to P. sorghi.

PMID- 22665187
TI  - Genetic mapping of maize streak virus resistance from the Mascarene source. I.
      Resistance in line D211 and stability against different virus clones.
AB  - Maize streak virus (MSV) disease may cause significant grain yield reductions in
      maize in Africa. Reunion island maize germplasm is a proven source of strong
      resistance. Its genetic control was investigated using 123 RFLP markers in an
      F(2) population of D211 (resistant) * B73 (susceptible). This population of 165
      F(2:3) families was carefully evaluated in Harare (Zimbabwe) and in Reunion.
      Artificial infestation was done with viruliferous leafhoppers. Each plant was
      rated weekly six times after infestation on a 1-9 scale previously adjusted by
      image analysis. QTL analyses were conducted for each scoring date, and for the
      areas under the disease, incidence and severity progress curves. The composite
      interval mapping method used allowed the estimation of the additive and dominance
      effects and QTL * environment interactions. Heritabilities ranged from 73% to
      98%, increasing with time after infestation. Resistance to streak virus in D211
      was provided by one region on chromosome 1, with a major effect, and four other
      regions on chromosomes 2, 3 (two regions) and 10, with moderate or minor effects.
      Overall, they explained 48-62% of the phenotypic variation for the different
      variables. On chromosome 3, one of the two regions seemed to be more involved in
      early resistance, whereas the second was detected at the latest scoring date.
      Other QTLs were found to be stable over time and across environments. Mild QTL *
      environment interactions were detected. Global gene action appeared to be
      partially dominant, in favor of resistance, except at the earliest scoring dates,
      where it was additive. From this population, 32 families were chosen,
      representing the whole range of susceptibility to MSV. They were tested in
      Reunion against three MSV clones, along with a co-inoculation of two of them.
      Virulence differences between clones were significant. There were genotype *
      clone interactions, and these were more marked for disease incidence than for
      severity. Although these interactions were not significant for the mean disease
      scores, it is suggested that breeders should select for completely resistant
      genotypes.

PMID- 22665188
TI  - Genetic mapping of maize streak virus resistance from the Mascarene source. II.
      Resistance in line CIRAD390 and stability across germplasm.
AB  - The streak disease has a major effect on maize in sub-Saharan Africa. Various
      genetic factors for resistance to the virus have been identified and mapped in
      several populations; these factors derive from different sources of resistance.
      We have focused on the Reunion island source and have recently identified several
      factors in the D211 line. A second very resistant line, CIRAD390, was crossed to
      the same susceptible parent, B73. The linkage map comprised 124 RFLP markers, of
      which 79 were common with the D211*B73 map. A row-column design was used to
      evaluate the resistance to maize streak virus (MSV) of 191 F(2:3) families under
      artificial infestation at two locations: Harare (Zimbabwe) and in Reunion island.
      Weekly ratings of resistance were taken and disease incidence and severity
      calculated. QTL analyses were conducted for each scoring date and for the
      integration over time of the disease scores, of incidence, and of severity.
      Heritability estimates (71-98%) were as high as for the D211*B73 population.
      Eight QTLs were detected on chromosomes 1, 2, 3, 5 (two QTLs), 6, 8, and 10. The
      chr1-QTL explained the highest proportion of phenotypic variation, about 45%. The
      QTLs on chromosomes 1, 2, and 10 were located in the same chromosomal bin as QTLs
      for MSV resistance in the D211*B73 population. In a simultaneous fit, QTLs
      explained together 43-67% of the phenotypic variation. The QTLs on chromosomes 3,
      5, and 6 appeared to be specific for one or the other component of the
      resistance. For the chr3-QTL, resistance was contributed by the susceptible
      parent. There were significant QTL * environment interactions for some of the
      variables studied, but QTLs were stable in the two environments. They also
      appeared to be stable over time. Global gene action ranged from partial dominance
      to overdominance, except for disease severity. Some additional putative QTLs were
      also detected. The major QTL on chromosome 1 seemed to be common to the other
      sources of resistance, namely Tzi4, a tolerant line from IITA, and CML202 from
      CIMMYT. However, the distribution of the other QTLs within the genome revealed
      differences in Reunion germplasm and across these other resistance sources. This
      diversity is of great importance when considering the durability of the
      resistance.

PMID- 22665189
TI  - Development of a molecular marker for the adult plant leaf rust resistance gene
      Lr35 in wheat.
AB  - The objective of this work was to develop a marker for the adult plant leaf rust
      resistance gene Lr35. The Lr35 gene was originally introgressed into chromosome
      2B from Triticum speltoides, a diploid relative of wheat. A segregating
      population of 96 F( 2 )plants derived from a cross between the resistant line
      ThatcherLr35 and the susceptible variety Frisal was analysed. Out of 80 RFLP
      probes previously mapped on wheat chromosome 2B, 51 detected a polymorphism
      between the parents of the cross. Three of them were completely linked with the
      resistance gene Lr35. The co-segregating probe BCD260 was converted into a PCR
      based sequence-tagged-site (STS) marker. A set of 48 different breeding lines
      derived from several European breeding programs was tested with the STS marker.
      None of these lines has a donor for Lr35 in its pedigree and all of them reacted
      negatively with the STS marker. As no leaf rust races virulent on Lr35 have been
      found in different areas of the world, the STS marker for the Lr35 resistance
      gene is of great value to support the introgression of this gene in combination
      with other leaf rust (Lr) genes into breeding material by marker-assisted
      selection.

PMID- 22665190
TI  - Quantitative trait loci associated with resistance to Fusarium head blight and
      kernel discoloration in barley.
AB  - Resistance to Fusarium head blight (FHB), deoxynivalenol (DON) accumulation, and
      kernel discoloration (KD) in barley are difficult traits to introgress into elite
      varieties because current screening methods are laborious and disease levels are
      strongly influenced by environment. To improve breeding strategies directed
      toward enhancing these traits, we identified genomic regions containing
      quantitative trait loci (QTLs) associated with resistance to FHB, DON
      accumulation, and KD in a breeding population of F(4:7) lines using restriction
      fragment length polymorphic (RFLP) markers. We evaluated 101 F(4:7) lines,
      derived from a cross between the cultivar Chevron and an elite breeding line,
      M69, for each of the traits in three or four environments. We used 94 previously
      mapped RFLP markers to create a linkage map. Using composite interval mapping, we
      identified 10, 11, and 4 QTLs associated with resistance to FHB, DON
      accumulation, and KD, respectively. Markers flanking these QTLs should be useful
      for introgressing resistance to FHB, DON accumulation, and KD into elite barley
      cultivars.

PMID- 22665191
TI  - Intergeneric somatic hybrids of rice [Oryza sativa L. (+) Porteresia coarctata
      (Roxb.) Tateoka].
AB  - Somatic hybrid plants were obtained following the electrofusion of rice (Oryza
      sativa L. cv 'Taipei 309', 2n = 2x = 24) cell suspension-derived protoplasts with
      non-dividing leaf protoplasts of Porteresia coarctata (2n = 4x = 48), a saline
      tolerant wild species. Fusion-treated protoplasts were plated on the surface of
      cellulose nitrate filter membranes, overlaying Lolium multiflorum nurse cells.
      The nurse cells were embedded in KPR medium containing 0.5 mg l(-1) 2,4
      dichlorophenoxyacetic acid and semi-solidified with SeaPlaque agarose. Putative
      somatic hybrid cell colonies were selected on the basis of their growth, whereby
      faster growing colonies were transferred preferentially to MS-based medium with
      2.0 mg l(-1) kinetin, 0.5 mg l(-1)alpha-naphthaleneacetic acid, 30 g l(-1)
      sucrose and 4.0 g l(-1) SeaKem agarose to induce shoot regeneration. One hundred
      and nineteen regenerated plants were micropropagated clonally on MS-based medium
      containing 2.0 mg l(-1) 6-benzylaminopurine, 50 g l(-1) sucrose and 4.0 g l(-1)
      SeaKem agarose, prior to DNA extraction of plant samples. Putative somatic
      hybrids were initially identified by RAPD analysis, and 8 plant lines were
      selected for further investigation by flow cytometric ploidy determination and
      cytology. Plants of one line had an allohexaploid chromosome complement (2n = 6x
      = 72) and, following examination of its vegetative clones by GISH, were confirmed
      as somatic hybrids containing full chromosome complements of both O. sativa and
      P. coarctata.

PMID- 22665192
TI  - Complex relation between triazine-susceptible phenotype  and genotype in the weed
      Senecio vulgaris may be caused  by chloroplast DNA polymorphism.
AB  - The weed Senecio vulgaris acquired high levels of resistance to triazine
      herbicides soon after the latter's introduction. As in most weeds, triazine
      resistance is conferred by a point mutation in the chloroplast psbA gene that
      negatively affects the fitness of its carrier. To assess levels of triazine
      resistance in S. vulgaris field populations, we adopted a PCR-RFLP-based
      molecular diagnostic test recently developed for the triazine resistance
      conferring region of the psbA gene of other weeds, including Brassica napus,
      Chenopodium spp. and Amaranthus spp., and compared these molecular results to the
      phenotypic response after triazine application. A highly significant linear
      correlation was found between phytotoxic symptoms and biomass reduction.
      Variability in phenotypic response was not only found between populations or
      inbred lines of S. vulgaris but also within replicates of the same inbred line.
      No clear relationship, however, was found between the DNA restriction pattern and
      the phenotypic response to triazine application, thereby throwing doubt on the
      use of such molecular diagnostic tests to track triazine resistance in S.
      vulgaris. Our results indicate that the chloroplast genome of S. vulgaris is
      polymorphic and that the level of polymorphism may be variable within single
      leaves of individual plants. We discuss the possible genetic basis of this
      polymorphism and its consequence for the acquisition and inheritance of
      chloroplast-based traits.

PMID- 22665193
TI  - Increased stable inheritance of herbicide resistance  in transgenic lettuce
      carrying a petE promoter-bar gene compared  with a CaMV 35S-bar gene.
AB  - Inheritance of resistance to herbicide  (300 mg/l glufosinate ammonium) up to the
      third (T3) seed generation was compared in two populations of transgenic lettuce
      (Lactuca sativa L. cv 'Evola') harbouring a T-DNA containing the bar gene, linked
      to either the Cauliflower Mosaic Virus (CaMV) 35S promoter, or a -784-bp
      plastocyanin promoter from pea (petE). Only 2.5% (4/163) of CaMV 35S-bar plants,
      selected by their kanamycin resistance(T0 generation), transmitted herbicide
      resistance at high frequency to their T3 seed generation compared with 97%
      (29/30) for kanamycin resistant petE-bar plants. In the case of 35S-bar
      transformants, only 16% (341/2,150) of the first seed generation (T1) plants, 22%
      (426/1,935) T2 plants and 11% (1,235/10,949) T3 plants were herbicide-resistant.
      In contrast, 63% (190/300) T1 plants, 83% (2,370/2,845) T2 plants and 99%
      (122/123) T3 petE-bar transformed plants were resistant to glufosinate ammonium.
      The T-DNAs carrying the petE-bar and CaMV 35S-bar genes also contained a CaMV 35S
      neomycin phosphotransferase (nptII) gene. ELISA showed that NPTII protein was
      absent in 29% (45/156) of the herbicide-resistant T2 plants from 8/19 herbicide
      resistant petE-bar lines. This indicated specific inactivation of the CaMV 35S
      promoter on the same T-DNA locus as an active petE promoter. The choice of
      promoter and T-DNA construct are crucial for long-term expression of transgenes
      in lettuce.

PMID- 22665194
TI  - QTL mapping of resistance to Sporisorium reiliana in maize.
AB  - We mapped and characterized quantitative trait loci (QTL) for resistance to
      Sporisorium reiliana. A population of 220 F(3) families produced from the cross
      of two European elite inbreds (D32, D145) was evaluated with two replications at
      a French location with high natural incidence of S. reiliana and at a Chinese
      location employing artificial inoculation. The 220 F(3) families were genotyped
      with 87 RFLP and seven SSR markers. Using composite interval mapping, we
      identified two different sets of 3 and 8 QTL for the French and the Chinese
      locations explaining 13% and 44% of respectively. Individual QTL explained up to
      14% of sigma^(2) (p). The 11 QTL mapped to eight maize chromosomes and displayed
      mostly additive or partial dominant gene action. Significant digenic epistatic
      interactions were detected for one pair of these QTL. Only a few QTL for S.
      reiliana were in common with QTL for resistance to Ustilago maydis and Puccinia
      sorghi, identified at a German location for the same population. Consequently, in
      our materials resistance to these three fungal pathogens of maize seems to be
      inherited independently.

PMID- 22665195
TI  - A genetic linkage map of tef [Eragrostis tef (Zucc.) Trotter] based on amplified
      fragment length polymorphism.
AB  - A genetic linkage map of tef was constructed with amplified fragment length
      polymorphism (AFLP) markers using F(5) recombinant inbred lines (RILs) derived by
      single seed descent from the intraspecific cross of 'Kaye Murri'*'Fesho'. A total
      of 192 EcoRI/MseI primer combinations were screened for parental polymorphism.
      Around three polymorphic fragments per primer combination were detected,
      indicating a low polymorphism level in tef. Fifty primer combinations were
      selected to assay the mapping population, and 226 loci segregated among 85 F(5)
      RILs. Most AFLP loci behaved as dominant markers (presence or absence of a band),
      but about 15% of the loci were codominant. Significant deviations from the
      expected Mendelian segregation ratio were observed for 26 loci. The genetic
      linkage map comprised 211 markers assembled into 25 linkage groups and covered
      2,149 cM of genome. AFLP is an efficient marker system for mapping plant species
      with low polymorphism such as tef. This is the first genetic linkage map
      constructed for tef. It will facilitate the mapping of genes controlling
      agronomically important traits and cultivar improvement in tef.

PMID- 22665196
TI  - Characterization of sexual progenies of male-sterile somatic cybrids between
      Brassica napus and Brassica tournefortii.
AB  - Cytogenetic studies were performed on four male-sterile progenies derived from
      four different cybrids produced between Brassica napus and B. tournefortii using
      the donor-recipient protoplast fusion method. The objective of these studies was
      to characterize the nuclear constitution of the plants. Mitotic investigation
      revealed that three of the four male-sterile lines had 38 chromosomes, which is
      equal to that of B. napus. The fourth line, C6, had variable chromosome numbers,
      ranging from 39 to 42 in different plants. The meiotic behavior in each progeny
      varied distinctly. Of the plants having 38 chromosomes, fairly high chromosome
      pairing, on average 18.08 bivalents per cell, was detected at metaphase-I.
      However, univalents with an average of 1.39 per cell, and very low frequencies of
      trivalents and/or tetravalents, were also observed in the lines. These results
      revealed that male-sterile cybrid lines were obtained with 38 chromosomes and a
      relatively high level of chromosome-pairing ability, indicating their potential
      for establishing a stable male-sterile rapeseed line.

PMID- 22665197
TI  - Interpreting genotype * environment interaction  in tropical maize using linked
      molecular markers  and environmental covariables.
AB  - An understanding of the genetic and environmental basis of genotype*environment
      interaction (GEI) is of fundamental importance in plant breeding. In mapping
      quantitative trait loci (QTLs), suitable genetic populations are grown in
      different environments causing QTLs*environment interaction (QEI). The main
      objective of the present study is to show how Partial Least Squares (PLS)
      regression and Factorial Regression (FR) models using genetic markers and
      environmental covariables can be used for studying QEI related to GEI. Biomass
      data were analyzed from a multi-environment trial consisting of 161 lines from a
      F(3:4) maize segregating population originally created with the purpose of
      mapping QTLs loci and investigating adaptation differences between highland and
      lowland tropical maize. PLS and FR methods detected 30 genetic markers (out of
      86) that explained a sizeable proportion of the interaction of maize lines over
      four contrasting environments involving two low-altitude sites, one intermediate
      altitude site, and one high-altitude site for biomass production. Based on a
      previous study, most of the 30 markers were associated with QTLs for biomass and
      exhibited significant QEI. It was found that marker loci in lines with positive
      GEI for the highland environments contained more highland alleles, whereas marker
      loci in lines with positive GEI for intermediate and lowland environments
      contained more lowland alleles. In addition, PLS and FR models identified maximum
      temperature as the most-important environmental covariable for GEI. Using a
      stepwise variable selection procedure, a FR model was constructed for GEI and QEI
      that exclusively included cross products between genetic markers and
      environmental covariables. Higher maximum temperature in low- and intermediate
      altitude sites affected the expression of some QTLs, while minimum temperature
      affected the expression of other QTLs.

PMID- 22665198
TI  - AFLP analysis of genetic relationships among the cultivated eggplant,
      Solanummelongena L., and wild relatives (Solanaceae).
AB  - The AFLP technique of DNA analysis was evaluated as a tool for assessing genetic
      relationships among the cultivated eggplant, S. melongena, and related species
      [Solanum L. subgenus Leptostemonum (Dunal) Bitter, section Melongena (Mill.)
      Dunal, series Incaniformia Bitter]. Genetic distances based on the AFLP data were
      estimated for 49 samples of 36 distinct accessions. Phenetic trees were
      constructed using Jaccard's coefficient and UPGMA, and other clustering methods:
      they all had very high co-phenetic correlation values, and were found to be
      consistent with previous trees based on other data types, in particular ITS-1
      sequences, isozymes and morphology, carried out on the same accessions. These
      results indicated that the AFLP technique is both an efficient and effective tool
      for determining genetic relationships among species of Solanum. A new
      classification is proposed for series Incaniformia.

PMID- 22665199
TI  - AFLP analysis of genetic relationships in the tribe Datureae (Solanaceae).
AB  - The AFLP technique was evaluated as a tool for assessing species relationships
      within the tribe Datureae and genetic distances were estimated for 47 accessions
      of over 12 species. The phenetic trees from various analyses of the AFLP data
      gave very high co-phenetic correlation values, and were found to be consistent
      with previous trees based on the analysis of different data types, in particular
      ITS-1 sequences, isozymes and morphology, carried out on the same accessions.
      These results indicated that the AFLP technique is both an efficient and
      effective tool for determining genetic relationships among taxa in the
      Solanaceae. A new classification is proposed for the tribe Datureae, which
      maintains the arborescent species as a separate genus, Brugmansia, and recognises
      three sections within the genus Datura; Stramonium, Dutra and Ceratocaulis. D.
      discolor, previously placed in section Dutra, was found to be intermediate
      between sections Dutra and Stramonium.

PMID- 22665200
TI  - The three important traits for cooking and eating quality of rice grains are
      controlled by a single locus in an elite rice hybrid, Shanyou 63.
AB  - The cooking and eating quality of the rice grain is one of the most serious
      problems in many rice-producing areas of the world. In this study, we conducted a
      molecular marker-based genetic analysis of three traits, amylose content (AC),
      gel consistency (GC) and gelatinization temperature (GT), that are the most
      important constituents of the cooking and eating quality of rice grains. The
      materials used in the analysis included F(2) seeds, an F(2:3) population, and an
      F(9) recombinant inbred-line population from a cross between the parents of
      'Shanyou 63', the most widely grown hybrid in rice production in China.
      Segregation analyses of these three generations showed that each of the three
      traits was controlled by a single Mendelian locus. Molecular marker-based QTL
      (quantitative trait locus) analyses, both by one-way analysis of variance using
      single marker genotypes and by whole-genome scanning with MAPMAKER/QTL, revealed
      a single locus that controls the expression of all three traits. This locus
      coincided with the Wx region on the short arm of chromosome 6, indicating that
      all three traits were either controlled by the Wx locus or by a genomic region
      tightly linked to this locus. This finding has provided clues to resolving the
      molecular bases of GC and GT in future studies. The results also have direct
      implications for the quality improvement of rice varieties.

PMID- 22665201
TI  - QTLs for resistance to Setosphaeria turcica in an early  maturing Dent*Flint
      maize population.
AB  - Quantitative trait loci (QTLs) for resistance to the fungal pathogen Setosphaeria
      turcica, the cause of northern corn leaf blight (NCLB), were mapped in a
      population of 220 F(3) families derived from a cross between two moderately
      resistant European inbred lines, D32 (dent) and D145 (flint). The population was
      genotyped with 87 RFLP and 7 SSR markers. Trials were conducted in the field in
      Switzerland, and in the greenhouse with selected F(3) families in Germany. The
      F(3) population segregated widely for resistance with transgression of the
      parents. By composite interval mapping, a total of 13 QTLs were detected with two
      disease ratings (0 and 3 weeks after flowering). Together these QTLs explained
      48% and 62% of the phenotypic variation. Gene action at most QTLs was partially
      dominant. Eight out of the 13 QTL alleles for resistance were contributed by the
      more-resistant parent, D145. On chromosomes 3, 5 and 8, QTLs were located in the
      same chromosomal regions as QTLs in tropical and U.S. Corn Belt germplasm. Some
      QTLs affected NCLB, head smut and common rust at the same time, with alleles at
      these loci acting isodirectionally.

PMID- 22665202
TI  - Comparative mapping in loblolly and radiata pine  using RFLP and microsatellite
      markers.
AB  - Genetic linkage maps were constructed for loblolly pine (Pinus taeda L.) and
      radiata pine (P. radiata D. Don) using a common set of RFLP and microsatellite
      markers. The map for loblolly pine combined data from two full-sib families and
      consisted of 20 linkage groups covering 1281 cM. The map for radiata pine had 14
      linkage groups and covered 1223 cM. All of the RFLP probes readily hybridise
      between loblolly and radiata pine often producing similar hybridisation patterns.
      There were in total 60 homologous RFLP loci mapped in both species which could be
      used for comparative purposes. A set of 20 microsatellite markers derived from
      radiata pine were also assayed; however, only 9 amplified and revealed
      polymorphic loci in both species. Single-locus RFLP and microsatellite markers
      were used to match up linkage groups and compare order between species. Twelve
      syntenic groups were obtained each consisting of from 3 to 9 homologous loci. The
      order of homologous loci was colinear in most cases, suggesting no major
      chromosomal rearrangements in the evolution of these species. Comparative mapping
      between loblolly and radiata pine should facilitate genetic research in both
      species and provide a framework for mapping in other pine species.

PMID- 22665203
TI  - Genetic control of high stearic acid content in the seed oil of the sunflower
      mutant CAS-3.
AB  - A sunflower mutant, CAS-3, with about 25% stearic acid (C18:0) in the seed oil
      was recently isolated after a chemical-mutagen treatment of RDF-1-532 seeds (8%
      C18:0). To study the inheritance of the high C18:0 content, CAS-3 was
      reciprocally crossed to RDF-1-532 and HA-89 (5% C18:0). Significant reciprocal
      cross differences were found in one of the two crosses, indicating possible
      maternal effects. In the CAS-3 and RDF-1-532 crosses, the segregation patterns of
      the F(1), BC(1), and F(2) populations fitted a one-locus (designated Es1) model
      with two alleles (Es1, es1) and with partial dominance of low over high C18:0
      content. Segregation patterns in the CAS-3 and HA-89 crosses indicated the
      presence of a second independent locus (designated Es2) with two alleles (Es2,
      es2), also with partial dominance of low over high C18:0 content. From these
      results, the proposed genotypes (C18:0 content) of each parent were as follows:
      CAS-3 (25.0% C18:0) =es1es1es2es2; RDF-1-532 (8.0% C18:0) =Es1Es1es2es2; and HA
      89 (4.6% C18:0) =Es1Es1Es2Es2. The relationship between the proposed genotypes
      and their C18:0 content indicates that the Es1 locus has a greater effect on the
      C18:0 content than the Es2 locus. Apparently, the mutagenic treatment caused a
      mutation of Es1 to es1 in RDF-1-532.

PMID- 22665204
TI  - Molecular mapping of two dwarfing genes differing in their GA response on
      chromosome 2H of barley.
AB  - The two recessive dwarfing mutants gai (GA-ins) and gal (GA-less), differing in
      their response to exogenously applied gibberellic acid (GA(3)), were mapped in
      the centromere region and on the long arm, respectively, of the barley chromosome
      2H. The gene gai, which determines reduced plant height and GA insensitivity
      pleiotropically, was found to co-segregate with the two RFLP markers Xmwg2058 and
      Xmwg2287. Both markers are known to map close to the centromere. The GA-sensitive
      dwarfing gene gal was found to be linked to the three co-segregating RFLP markers
      Xmwg581, Xmwg882 and Xmwg2212 (proximal) and XksuG5 (distal) by 3.6 and 9.5. cM,
      respectively. The distance between the two mutant loci was estimated to be about
      55 cM. Homoeologous relationships between the dwarfing genes within the Triticeae
      are discussed.

PMID- 22665205
TI  - Transformation of the limonene synthase gene into peppermint (Mentha piperita L.)
      and preliminary studies on the essential oil profiles of single transgenic
      plants.
AB  - Agrobacterium-mediated and direct gene transfer into protoplasts using PEG were
      both successfully used to produce stable, transformed peppermint plants
      (Mentha*piperita L. cultivar Black Mitcham) with the limonene synthase gene. Stem
      internode explants found to possess a high level of organogenesis through
      adventitious shoot formation were subjected to Agrobacterium tumefaciens disarmed
      strain GV3101 (pMP90). Following the development of an efficient protoplast-to
      plant cycle from stem-isolated protoplasts, they were used in direct gene
      transformations. In both cases the binary vector pGA643 carrying the nptII/GUS
      genes, both driven by the CaMV35S promoter, was used in preliminary plant
      transformation studies. Later, GUS was replaced with the limonene synthase gene.
      Kanamycin was used as a selective agent in all transformation experiments to
      obtain both transformed protoplast-derived calli as well as putative transgenic
      shoots regenerated from internode explants. Both types of transformation resulted
      in transgenic plants which were detected using PCR and confirmed by Southern-blot
      hybridizations. Southern analysis revealed that the method of Agrobacterium
      mediated transformation is superior to the direct DNA uptake into protoplasts
      with regard to the stability of the insert during the transformation event.
      Single transgenic plants were grown to 10% flowering in a greenhouse and the
      plants derived both by the Agrobacterium and the protoplast-derived methods were
      generally observed to have essential oil profiles characterized by a high
      menthone, low-menthol, high-menthofuran and -pulegone content in comparison to a
      typical mid-west peppermint. Limonene varied only slightly, around 1.2%, in
      transgenic plants produced by both methods.

PMID- 22665206
TI  - Genetic bases of instability of male sterility and fertility reversibility in
      photoperiod-sensitive genic male-sterile rice.
AB  - Photoperiod-sensitive genetic male-sterile (PSGMS) rice, with its male fertility
      regulated by photoperiod length, is very useful for hybrid rice development.
      However, breeding for new PSGMS lines has faced two major difficulties - the
      stability of male sterility and the reversibility of male fertility. In this
      study we assessed the genetic bases of stability of sterility and fertility
      reversibility using a molecular marker-based approach. A cross was made between
      two newly bred PSGMS lines: Peiai 64S, which has a stable sterility but is
      difficult to reverse to fertility, and 8902S, which has a unstable sterility but
      is easy to reverse to fertility. The fertility of the parents and of the F(1) and
      F(2) populations was repeatedly examined under 11 different long-day and short
      day conditions. The genetic effects were assayed by interval mapping and two-way
      analyses of variance using the F(2) data of 128 polymorphic loci representing all
      the 12 rice chromosomes. The analyses resolved a number of single-locus QTLs and
      two-locus interactions under both long-day and short day conditions. The
      interactions involved a large number of loci, most of which were not detectable
      on a single-locus basis. The results showed that the genetic bases of both
      stability of sterility and reversibility of fertility are the joint effects of
      the additive effects of the QTLs and additive-by-additive components of two-locus
      interactions. The implications of these findings in hybrid rice development are
      also discussed.

PMID- 22665207
TI  - Production and cytogenetics of intergeneric hybrids between the three cultivated
      Brassica diploids and Orychophragmusviolaceus.
AB  - It has been proposed that both complete and partial separation of the parental
      genomes during mitosis and meiosis occurs in the intergeneric hybrids between
      Orychophragmus violaceus (2n=24) and the three cultivated Brassica tetraploids
      (B. napus, B. carinata and B. juncea). The hypothesis has been that this and the
      variations in chromosome numbers of these hybrids and their progenies result from
      the different roles of the A, B and C genomes originating from Brassica. To test
      this hypothesis, we produced hybrids between O. violaceus and the cultivated
      Brassica diploids. The hybrids with B. oleracea (2n=18, CC) had an intermediate
      morphology, but their petals were purple like those of O. violaceus. They were
      sterile and had the expected chromosome number (2n=21) in their mitotic and
      meiotic cells. The hybrid with B. campestris (2n=20, AA) was morphologically
      intermediate, except for its partial fertility and its yellow petals, which were
      similar to those of B. campestris. It was mixoploid (2n=23-42), and cells with
      2n=34 were most frequent. Partial separation of parental genomes during mitosis,
      leading to the addition of O. violaceus chromosomes to the B. campestris
      complement, was proposed to explain the findings in the mitotic and meiotic cells
      of the hybrid and its progeny. In crosses with B. nigra (2n=16, BB), the majority
      of the F(1) plants were of the maternal type (2n=16), a small fraction had B.
      nigra morphology but were mixoploids (2n=16-18), predominantly with 2n=16 cells
      and three plants, each with a specific morphology, were mixoploids consisting of
      cells with varying ranges of chromosome numbers (2n=17-26, 11-17 and 14-17). The
      origin of these different types of plants was inferred to be a result of the
      complete and partial separation of parental genomes and the loss of O. violaceus
      chromosomes. Our findings in the three crosses suggest that the A genome was more
      influential than the C genome with respect to complete genome separation during
      mitosis and meiosis of the hybrids with B. napus. Possible complete and partial
      genome separation during mitotic divisions of the hybrids with B. carinata was
      mainly attributed to the role of the B genome. The combined roles of the A and B
      genomes would thus contribute to the most variable chromosome numbers of mitotic
      and meiotic cells in the hybrids with B. juncea and their progenies. The possible
      cytological mechanisms pertaining to these hybrids and the potential of genome
      separation in the production of Brassica aneuploids and homozygous plants are
      discussed.

PMID- 22665208
TI  - Average effect of a mutation in lignin biosynthesis in loblolly pine.
AB  - Cinnamyl alcohol dehydrogenase (CAD, E.C. 1.1.1.195) is a monolignol biosynthetic
      enzyme that catalyzes the final step of lignin subunit biosynthesis in higher
      plants. Recently, a mutant allele of the cad gene, cad-n1, encoding for the CAD
      enzyme, was discovered in loblolly pine. By reducing the expression of the cad
      gene, this mutant has a decreased lignin content and major changes in the lignin
      composition in wood. In this study, we found that the substitution of a wild-type
      allele by cad-n1 was associated with a significant effect on 2nd-year shoot
      elongation in a half-sib family of loblolly pine (designated family 7-1037). The
      average effect of cad-n1 appeared to increase with tree growth and was greater
      for stem radial growth than height growth. An increase of 14.1% in de-barked
      volume in year 4 was associated with cad-n1. Co-segregation analysis indicated
      that the cad locus itself might represent a gene that governs stem growth in
      pine. The significance of the mutation cad-n1 for tree growth and wood processing
      is discussed.

PMID- 22665209
TI  - A genetic model and molecular markers for wild oat (Avena fatua L.) seed
      dormancy.
AB  - Seed dormancy allows weed seeds to persist in agricultural soils. Wild oat (Avena
      fatua L.) is a major weed of cereal grains and expresses a range of seed dormancy
      phenotypes. Genetic analysis of wild oat dormancy has been complicated by the
      difficulty of phenotypic classification in segregating populations. Therefore,
      little is known about the nature of the genes that regulate dormancy in wild oat.
      The objectives of our studies were to develop methods to classify the germination
      responses of segregating wild oat populations and to find molecular markers
      linked to quantitative trait loci (QTL) that regulate seed dormancy in wild oat.
      RAPD markers OPX-06 and OPT-04 explained 12.6% and 6.8% respectively, of the F(2)
      phenotypic variance. OPF-17 was not significant in a simple regression model, but
      it was linked in repulsion to OPT-04. A three-locus model of seed dormancy in
      wild oat is presented based on the 41-day germination profiles of F(1), F(2),
      F(3), BC(1)P(1)F(1), BC(1)P(1)F(2), and BC(1)P(2)F(1) generations, and the 113
      day germination profile of 126 F(7) recombinant inbred lines. Loci G (1) and G
      (2) promote early germination, and the D locus promotes late germination. If at
      least one copy of the dominant G (1) or G (2 )alleles are present regardless of
      the genotype at D locus, then the individual will be nondormant. If the genotype
      is g (1) g (1) g (2) g (2) D_, then the phenotype will be dormant.

PMID- 22665210
TI  - Diversity in inhibitors of trypsin and Helicoverpa armigera gut proteinases in
      chickpea (Cicer arietinum) and its wild relatives.
AB  - Developing seeds of eight chickpea (Cicer arietinum L.) cultivars (12-60 days
      after flowering) showed a significant variation in the trypsin inhibitor (TI) and
      the Helicoverpa armigera gut proteinase inhibitor (HGPI) content. For example,
      the highest TI (198 units/g) and HGPI (23 units/g) activities were exhibited by
      mature seeds of cv ICCV-2, whereas the lowest inhibitor activities were observed
      in cv PG8505-7 (96.1 TI units/g) and cv Vijay (5 HGPI units/g). Electrophoretic
      patterns showed a variation in TI bands during the early stages of seed
      development, indicating cultivar-specific TI accumulation. Among the seed organs,
      TI and HGPI activities were highly localized in the embryo-axis as compared to
      the cotyledons in immature and mature seeds. Moisture stress, as effected under
      rainfed conditions, resulted in reduced PI levels. Wild relatives of chickpea
      revealed variability in terms of the number and intensity of TI bands. However,
      when assessed for inhibition of HGP, none of the wild Cicer species showed more
      than 35% inhibition, suggesting that a large proportion of HGP was insensitive to
      PIs from Cicer. Our results provide a biochemical basis for the adaptation of H.
      armigera to the PIs of Cicer species and advocate the need for the transformation
      of chickpea with a suitable gene(s) for H. armigera resistance.

PMID- 22665211
TI  - RFLP mapping of BaYMV resistance gene rym3 in barley  (Hordeum vulgare).
AB  - The rym3 (formerly designated ym3) gene conferring resistance to barley yellow
      mosaic virus (BaYMV) is effective against all strains of the virus but up to now
      has not been mapped to any chromosome. We performed a linkage analysis, using DNA
      extracted from individually harvested mature leaves of 153 F(2) plants derived
      from a cross between BaYMV-resistant cv 'Ishuku Shirazu' carrying rym3 and
      susceptible cv 'Ko A'. Additionally, the F(3) lines derived from F(2) plants were
      grown in the BaYMV-infested field and examined for their reaction to BaYMV. Our
      results indicated that rym3 is located on the short arm of chromosome 5H and
      flanked by RFLP markers MWG28and ABG705A at distances of 7.2 and 11.7 cM,
      respectively. The chromosomal configuration estimated by DNA markers around rym3
      and the utilization of these molecular markers for pyramiding with the BaYMV
      resistance genes in barley breeding programs are discussed.

PMID- 22665212
TI  - The use of microsatellites for germplasm management in a Portuguese grapevine
      collection.
AB  - To initiate the characterization of the Portuguese grapevine genepool, we have
      genotyped 49 Portuguese grapevine cultivars at 11 microsatellite loci. The
      markers proved to be informative in the Portuguese cultivars, with expected
      heterozygosity ranging from 0.67 to 0.84. At most loci, an excess of heterozygous
      individuals was observed, while the deficiency of heterozygotes at 1 locus
      (VVMD6) indicated the presence of null alleles. On the basis of the
      microsatellite allele data several previously assumed synonyms were verified: (1)
      'Fernao Pires'='Maria Gomes', (2) 'Moscatel de Setubal'='Muscat of Alexandria',
      (3) 'Boal Cachudo'='Boal da Madeira'='Malvasia Fina', (4) 'Siria'='Crato Branco'=
      'Roupeiro' and (5) 'Periquita'='Castelao Frances'='Joao de
      Santarem'='Trincadeira'. Although the three varieties 'Verdelho da Madeira',
      'Verdelho dos Acores', and 'Verdelho roxo' are regarded by the Lista Nacional de
      Sinonimos as distinct cultivars, they displayed identical SSR profiles at 17 loci
      and appear to represent types of 1 single cultivar. The genetic profiles of all
      49 cultivars were searched for possible parent-offspring groups. The data
      obtained revealed the descendence of 'Boal Ratinho' from 'Malvasia Fina' and
      'Siria'.

PMID- 22665213
TI  - Inheritance of resistance to beet necrotic yellow vein virus in Beta vulgaris
      conferred by a second gene for resistance.
AB  - Rhizomania is a serious disease of sugar beet, caused by beet necrotic yellow
      vein virus (BNYVV). The disease can only be controlled by the use of resistant
      cultivars. The accession Holly contains a single dominant gene for resistance,
      called Rz. The identification of a locus for resistance that differs from Rz
      would provide possibilities to produce cultivars with multiple resistance to
      BNYVV. Inheritance of resistance to BNYVV was studied by screening progenies of
      crosses between resistant plants of the accessions Beta vulgaris subsp. maritima
      WB42 and B. vulgaris subsp. vulgaris Holly-1-4 or R104. Observed and expected
      segregation ratios were compared to elucidate whether the resistance genes in the
      three accessions are alleles or situated on different loci. STS markers, linked
      to the genes for resistance, were used to study the segregation in more detail.
      The results demonstrated that the genes for resistance to BNYVV inHolly-1-4 and
      WB42 are closely linked. The gene for resistance in R104 is at the same locus as
      in Holly-1-4, and also closely linked to the gene in WB42. As the Holly
      resistance gene has been named Rz, the name Rz2 is proposed to refer to the
      resistance gene in WB42. Consequently, the gene Rz should be referred to as Rz1.

PMID- 22665214
TI  - The effect of bolus viscosity on laryngeal closure in swallowing: kinematic
      analysis using 320-row area detector CT.
AB  - The present study examined the effect of bolus viscosity on the onset of
      laryngeal closure (relative to hyoid elevation), the duration of laryngeal
      closure, and other key events of swallowing in ten healthy volunteers. All
      volunteers underwent 320-row area detector computed tomography swallow studies
      while swallowing 10 ml of honey-thick barium (5 % v/w) and thin barium (5 % v/w)
      in a 45 degrees  reclining position. Three-dimensional images of both
      consistencies were created in 29 phases at an interval of 0.10 s (100 ms) over a
      2.90-s duration. The timing of the motions of the hyoid bone, soft palate, and
      epiglottis; the opening and closing of the laryngeal vestibule, true vocal cords
      (TVC), and pharyngoesophageal segment; and the bolus movement were measured and
      compared between the two consistencies. The result showed differing patterns of
      bolus movement for thin and thick liquids. With thin liquids, the bolus reached
      the hypopharynx earlier and stayed in the hypopharynx longer than with thick
      liquids. Among events of laryngeal closure, only the timing of TVC closure
      differed significantly between the two consistencies. With thin liquids, TVC
      closure started earlier and lasted longer than with thick liquids. This TVC
      movement could reflect a response to the faster flow of thin liquids. The results
      suggest that bolus viscosity alters the temporal characteristics of swallowing,
      especially closure of the TVC.

PMID- 22665215
TI  - Fasting insulin levels and metabolic risk factors in type 2 diabetic patients at
      the first visit in Japan: a 10-year, nationwide, observational study (JDDM 28).
AB  - OBJECTIVE: To investigate the relationship between fasting insulin levels and
      metabolic risk factors (MRFs) in type 2 diabetic patients at the first
      clinic/hospital visit in Japan over the years 2000 to 2009. RESEARCH DESIGN AND
      METHODS: In total, 4,798 drug-naive Japanese patients with type 2 diabetes were
      registered on their first clinic/hospital visits. Conventional clinical factors
      and fasting insulin levels were observed at baseline within the Japan Diabetes
      Clinical Data Management (JDDM) study between consecutive 2-year groups. Multiple
      linear regression analysis was performed using a model in which the dependent
      variable was fasting insulin values using various clinical explanatory variables.
      RESULTS: Fasting insulin levels were found to be decreasing from 2000 to 2009.
      Multiple linear regression analysis with the fasting insulin levels as the
      dependent variable showed that waist circumference (WC), BMI, mean blood
      pressure, triglycerides, and HDL cholesterol were significant, with WC and BMI as
      the main factors. ANCOVA after adjustment for age and fasting plasma glucose
      clearly shows the decreasing trend in fasting insulin levels and the increasing
      trend in BMI. CONCLUSIONS: During the 10-year observation period, the decreasing
      trend in fasting insulin was related to the slight increase in WC/BMI in type 2
      diabetes. Low pancreatic beta-cell reserve on top of a lifestyle background might
      be dependent on an increase in MRFs.

PMID- 22665216
TI  - The relationship between brain volume and walking outcomes in older adults with
      and without diabetic peripheral neuropathy.
AB  - OBJECTIVE: Diabetic peripheral neuropathy (DPN) alters walking. Yet, the
      compensatory role of central locomotor circuits remains unclear. We hypothesized
      that walking outcomes would be more closely related to regional gray matter
      volumes in older adults with DPN as compared with nonneuropathic diabetic
      patients and nondiabetic control subjects. RESEARCH DESIGN AND METHODS:
      Clinically important outcomes of walking (i.e., speed, stride duration
      variability, and double support time) were measured in 29 patients with DPN (type
      2 diabetes with foot-sole somatosensory impairment), 68 diabetic (DM) patients
      (type 2 diabetes with intact foot-sole sensation), and 89 control subjects.
      Global and regional gray matter volumes were calculated from 3 Tesla magnetic
      resonance imaging. RESULTS: DPN subjects walked more slowly (P = 0.005) with
      greater stride duration variability (P < 0.001) and longer double support (P <
      0.001) as compared with DM and control subjects. Diabetes was associated with
      less cerebellar gray matter volume (P < 0.001), but global gray matter volume was
      similar between groups. DPN subjects with lower gray matter volume globally (P <
      0.004) and regionally (i.e., cerebellum, right-hemisphere dorsolateral prefrontal
      cortex, basal ganglia, P < 0.005) walked more slowly with greater stride duration
      variability and/or longer double support. Each relationship was stronger in DPN
      than DM subjects. In control subjects, brain volumes did not relate to walking
      patterns. CONCLUSIONS: Strong relationships between brain volumes and walking
      outcomes were observed in the DPN group and to a lesser extent the DM group, but
      not in control subjects. Individuals with DPN may be more dependent upon
      supraspinal elements of the motor control system to regulate several walking
      outcomes linked to poor health in elderly adults.

PMID- 22665217
TI  - Development and validation of the type 1 diabetes nutrition knowledge survey.
AB  - OBJECTIVE: The purpose of this study was to develop a survey of general and
      diabetes-specific nutrition knowledge for youth with type 1 diabetes and their
      parents and to assess the survey's psychometric properties. RESEARCH DESIGN AND
      METHODS: A multidisciplinary pediatric team developed the Nutrition Knowledge
      Survey (NKS) and administered it to youth with type 1 diabetes (n = 282, 49%
      females, 13.3 +/- 2.9 years) and their parents (82% mothers). The NKS content
      domains included healthful eating, carbohydrate counting, blood glucose response
      to foods, and nutrition label reading. Higher NKS scores reflect greater
      nutrition knowledge (score range is 0-100%). In youths, glycemic control was
      assessed by A1C, and dietary quality was determined by the Healthy Eating Index
      2005 (HEI-2005) derived from 3-day diet records. Validity was based on
      associations of NKS scores with A1C and dietary quality. Reliability was assessed
      using the Kuder-Richardson Formula 20 (KR-20) and correlations of domain scores
      to total score. RESULTS: Mean NKS scores (23 items) were 56.9 +/- 16.4% for youth
      and 73.4 +/- 12.5% for parents. The KR-20 was 0.70 for youth and 0.59 for
      parents, representing acceptable internal consistency of the measure. In
      multivariate analysis, controlling for youth age, family income, parent
      education, diabetes duration, and insulin regimen, parent NKS scores were
      associated with corresponding youth A1C (beta = -0.13, P = 0.03). Both parent
      (beta = 0.20, P = 0.002) and youth (beta = 0.25, P < 0.001) NKS scores were
      positively associated with youth HEI-2005 scores. CONCLUSIONS: The NKS appears to
      be a useful measure of general and diabetes-specific nutrition knowledge for
      youth with type 1 diabetes and their parents.

PMID- 22665218
TI  - A randomized study of decitabine versus conventional care for maintenance therapy
      in patients with acute myeloid leukemia in complete remission.

PMID- 22665219
TI  - Improvement in the purification process of the capsular polysaccharide from
      Haemophilus influenzae type b by using tangential ultrafiltration and
      diafiltration.
AB  - Capsular polysaccharide produced by Haemophilus influenzae b (Hib) is the main
      virulent agent and used as the antigen in the vaccine formulation. In this study,
      an improved process of polysaccharide purification was established based on
      tangential flow ultrafiltration using detergents (cocamidopropyl betaine and
      sodium deoxycholate), two selective ethanol precipitations steps, and extensive
      enzymatic hydrolysis as strategy. The relative purity (RP) related to protein and
      nucleic acids were 122~263 and 294~480, respectively, and compatible with the
      specifications established by the World Health Organization for Hib vaccine,
      RP>=100. These results make this process simple, cheaper, efficient,
      environmentally friendly, and prone to be scaled up.

PMID- 22665220
TI  - Editorial Note on: Observations in the diagnosis of cervical myelopathy in
      patients suffering from diabetes mellitus.

PMID- 22665221
TI  - International spinal cord injury spinal column injury basic data set.
AB  - STUDY DESIGN: Survey of expert opinion, feedback and final consensus. OBJECTIVES:
      To describe the development of the International Spinal Cord Injury (SCI) Spinal
      Column Injury Basic Data Set. SETTING: International working group. METHODS: A
      committee of experts was established to select and define data elements. The data
      set was then disseminated to the appropriate committees and organizations for
      comment. All suggested revisions were considered and the final version was
      endorsed by both the International Spinal Cord Society (ISCoS) and the American
      Spinal Injury Association (ASIA). RESULTS: The data set consists of seven
      variables: (1) penetrating or blunt injury, (2) spinal column injury(ies), (3)
      single or multiple level spinal column injury(ies), (4) spinal column injury
      level number, (5) spinal column injury level, (6) disc and/or posterior
      ligamentous complex injury and (7) traumatic translation. All variables are coded
      using numbers or characters. For variables 1, 2, 3, 4, 6 and 7, response
      categories are assigned a numeric point score. Variable 5 assigns both characters
      and numbers to identify level(s) of spinal injured vertebra(e). When there are
      several distinct and separate levels of injury, then each one is described using
      variables 4 through 7. CONCLUSION: The International SCI Spinal Column Injury
      Basic Data Set was developed to facilitate comparisons of spinal column injury
      data among studies, centres and countries. This data set is part of the National
      Institute of Neurological Disorders and Stroke Common Data Element project, and
      tools are now available to assist investigators in collecting this data in their
      SCI clinical studies.

PMID- 22665222
TI  - Prevalence of non-traumatic spinal cord injury in Victoria, Australia.
AB  - STUDY DESIGN: Forecasting using population modelling. OBJECTIVES: To determine
      the prevalence of non-traumatic spinal cord injury (NTSCI) on 30 June 2010.
      SETTING: Victoria, Australia. METHODS: Modelling used the following data:
      incidence of NTSCI based on state-wide, population-based, health-administration
      database of hospital admissions; state and national population profiles and life
      tables; levels of NTSCI based on national rehabilitation outcomes data; and life
      expectancy for persons with SCI. RESULTS: The total population prevalence rate
      was 367.2 per million, whereas the prevalence in adults aged 16 years and older
      was estimated to be 2027, equivalent to a population prevalence rate of 455 per
      million persons. There were more males (1097) with NTSCI (prevalence rate males
      197.8 per million population; females 169.1 per million population) and the
      prevalence was much higher among those with paraplegia (prevalence rate 269.3 per
      million compared to 97.8 per million with tetraplegia) and incomplete NTSCI.
      Ventilator dependency (prevalence rate 1.6 per million population) and paediatric
      NTSCI (prevalence rate 6 per million population <= 15 years old) were extremely
      rare. CONCLUSION: We have reported a method for calculating an estimate of the
      prevalence of NTSCI that provides information that will be vital to optimise
      health care planning for this group of highly disabled members of society. It is
      suggested that refinements to the modelling methods are required to enhance its
      reliability. Future projects should be directed at refining the mortality ratios
      and performing cohort survival studies.

PMID- 22665223
TI  - Staining protocols for human pancreatic islets.
AB  - Estimates of islet area and numbers and endocrine cell composition in the adult
      human pancreas vary from several hundred thousand to several million and beta
      mass ranges from 500 to 1500 mg. With this known heterogeneity, a standard
      processing and staining procedure was developed so that pancreatic regions were
      clearly defined and islets characterized using rigorous histopathology and
      immunolocalization examinations. Standardized procedures for processing human
      pancreas recovered from organ donors are described in part 1 of this series. The
      pancreas is processed into 3 main regions (head, body, tail) followed by
      transverse sections. Transverse sections from the pancreas head are further
      divided, as indicated based on size, and numbered alphabetically to denote
      subsections. This standardization allows for a complete cross sectional analysis
      of the head region including the uncinate region which contains islets composed
      primarily of pancreatic polypeptide cells to the tail region. The current report
      comprises part 2 of this series and describes the procedures used for serial
      sectioning and histopathological characterization of the pancreatic paraffin
      sections with an emphasis on islet endocrine cells, replication, and T-cell
      infiltrates. Pathology of pancreatic sections is intended to characterize both
      exocrine, ductular, and endocrine components. The exocrine compartment is
      evaluated for the presence of pancreatitis (active or chronic), atrophy,
      fibrosis, and fat, as well as the duct system, particularly in relationship to
      the presence of pancreatic intraductal neoplasia. Islets are evaluated for
      morphology, size, and density, endocrine cells, inflammation, fibrosis, amyloid,
      and the presence of replicating or apoptotic cells using H&E and IHC stains. The
      final component described in part 2 is the provision of the stained slides as
      digitized whole slide images. The digitized slides are organized by case and
      pancreas region in an online pathology database creating a virtual biobank.
      Access to this online collection is currently provided to over 200 clinicians and
      scientists involved in type 1 diabetes research. The online database provides a
      means for rapid and complete data sharing and for investigators to select blocks
      for paraffin or frozen serial sections.

PMID- 22665225
TI  - The major histocompatibility complex: a paradigm for studies of the human genome.
AB  - The major histocompatibility complex (MHC) on chromosome 6 is one of the most
      intensively studied regions of the human genome and has many features which make
      it unique. It is the source of much research interest because of its role in
      autoimmune and infectious disease susceptibility, and of diagnostic interest
      because of its role in transplantation and rejection. It is the most gene-dense
      and SNP-rich region of the genome, with large number of complex haplotypes and
      other features which must be taken into account when analysing the MHC in the
      laboratory. This article provides a brief overview of the MHC highlighting some
      of the issues that must be considered when developing new methods and assays.

PMID- 22665226
TI  - HLA typing by SSO and SSP methods.
AB  - Human leukocyte antigen (HLA) typing, utilising the sequence-specific
      oligonucleotide (SSO) and sequence-specific primer (SSP) technologies, has been
      in routine use in many tissue typing laboratories worldwide for more than 20
      years since the development of the polymerase chain reaction. Both methods are
      very useful for clinical and research purposes and can provide generic (low
      resolution) to allelic (high resolution) typing results. This chapter provides an
      overview of the SSO and SSP methods in relation to HLA typing.

PMID- 22665224
TI  - Increased pro-inflammatory cytokine production after lipopolysaccharide
      stimulation in patients with X-linked agammaglobulinemia.
AB  - PURPOSE: To evaluate the lipopolysaccharide (LPS)-induced pro-inflammatory
      cytokine response by peripheral blood mononuclear cells (PBMCs) from XLA
      patients. METHODS: Thirteen patients with XLA were included in the study. LPS
      induced TNF-alpha, IL-1beta, IL-6, and IL-10 production was determined in PBMCs
      from patients and matched healthy controls by ELISA. Cytokine production was
      correlated with the severity of mutation, affected domain and clinical
      characteristics. RESULTS: In response to LPS, PBMCs from XLA patients produced
      significantly higher amounts of pro-inflammatory cytokines and IL-10 compared to
      controls, and this production was influenced neither by the severity of the
      mutation nor the affected domain. PBMCs from patients with a history of more
      hospital admissions before their diagnosis produced higher levels of TNF-alpha.
      PBMCs from patients with lower serum IgA levels showed a higher production of TNF
      alpha and IL-1beta. Less severe (punctual) mutations in the Btk gene were
      associated with higher serum IgG levels at diagnosis. CONCLUSIONS: Our results
      demonstrate a predominantly inflammatory response in XLA patients after LPS
      stimulation and suggest a deregulation of TLR signaling in the absence of Btk.
      This response may be influenced by environmental factors.

PMID- 22665227
TI  - Methods for diagnostic HLA typing in disease association and drug
      hypersensitivity.
AB  - This chapter describes the application of diagnostic HLA typing for disease
      association and five methods used for specific HLA genotypes. The methods utilise
      a combination of polymerase chain reaction (PCR) amplification to detect sequence
      polymorphism by the presence or absence of amplification, nucleotide sequencing
      of the PCR product, and hybridisation of the PCR product with labelled probes.
      The probes are specific for sequence polymorphism associated with the genotype
      and are attached to either a Micro Bead or a Solid Phase. In addition, the
      detection of single nucleotide polymorphism(s) which "tag" for the genotype using
      a real-time PCR is described.

PMID- 22665228
TI  - HLA typing using bead-based methods.
AB  - The LABType((r)) SSO (One Lambda, Inc) and Gen-Probe LIFECODES HLA-SSO HLA Typing
      tests are rapid and efficient assays for determining human leukocyte antigens
      (HLAs). The principle of these assays involves the hybridization of reverse
      sequence-specific oligonucleotide probes each attached to a unique colour coded
      microsphere to identify HLA class I and class II alleles. Target DNA is
      polymerase chain reaction (PCR) amplified using group-specific primers and then
      biotinylated which allows it to be detected using R-Phycoerythrin-conjugated
      Streptavidin. The PCR product is then denatured and allowed to hybridise to
      complementary DNA probes conjugated to fluorescently code microsperes. The
      Luminex((r)) Flow Analyser achieves detection by determining the fluorescent
      intensity of PE on each microsphere. The assignment of HLA alleles is based on
      the reaction pattern of the various beads compared to patterns with known HLA
      alleles.

PMID- 22665229
TI  - HLA typing by direct DNA sequencing.
AB  - Sequencing-based typing is a high resolution method for the identification of HLA
      polymorphisms. The majority of HLA Class I alleles can be discriminated by their
      exon 2 and 3 sequence, and for Class II alleles, exon 2 is generally sufficient.
      There are polymorphic positions in other exons which may require additional
      sequencing to exclude certain alleles with differences outside exon 2 and 3,
      depending on the clinical requirement and relevant accredition guidelines. The
      process involves selective amplification of target alleles by PCR, agarose gel
      electrophoresis of the PCR products to assess the quantity and quality, followed
      by purification of PCR amplicons to remove excess primer and dNTPs. Cycle
      sequencing reactions using Applied BiosystemsTM BigDye((r)) Terminator Ready
      Reaction v1.1 or v3.1 Kit are performed, then purification of sequence reactions
      before electrophoresing using Applied BiosystemsTM 3730 or 3730XL Genetic
      Analyser (or similar). Data is processed by specialised software packages, which
      compare the sample sequence to the sequences of all possible theoretical allele
      combinations to assign an accurate genotype. Examination of all nucleotides, both
      at conserved and polymorphic positions enables the direct identification of new
      alleles, which may not be possible with techniques such as SSP and SSO typing.

PMID- 22665230
TI  - Data analysis of HLA sequencing using Assign-SBT v3.6+ from Conexio.
AB  - DNA Sequencing is now a standard frontline high-throughput HLA typing procedure
      with some unrelated bone marrow donor registry typing laboratories performing
      tens of thousands of tests per year. The advantage of DNA sequencing is that, by
      definition, sequencing directly identifies all bases in the DNA template.
      Alternative molecular-based assays such as the use of sequence-specific PCR
      primers (PCR-SSP) and oligonucleotide probes (PCR-SSO) provide information only
      for those regions to which the oligos are designed and no information is obtained
      for the regions between primers and probes.The era of routine high-throughput
      sequencing-based typing (SBT) was made possible by the development of locus
      specific PCR-based assays and the development of the HLA sequencing-based typing
      software, Assign-SBT v3.2.7 by Conexio Genomics. A single PCR per locus
      simplified the template preparation stage of the test and Assign-SBT simplified
      the sequence analysis and allele assignment stage. Together these developments
      dramatically simplified the SBT procedure, making SBT cost effective.This chapter
      provides a comprehensive description of Assign-SBT sequence analysis software for
      use in a HLA typing laboratory.

PMID- 22665231
TI  - Simple methods for the detection of HLA-G variants in coding and non-coding
      regions.
AB  - The non-classical human leukocyte antigen (HLA)-G plays a crucial role in the
      induction of tolerance at the feto-maternal interface as well as in
      transplantation, cancer, inflammation, and autoimmune diseases. To understand
      gene regulation and the impact of polymorphic sites on the function, simple and
      easy feasible approaches are needed for the detection of HLA-G variants in coding
      and non-coding regions. Here we summarize a set of methods for the identification
      of variants in the exon 2-4, in the 3' untranslated region and in the gene
      promoter region of the HLA-G gene.

PMID- 22665232
TI  - Molecular typing of HLA-E.
AB  - Human leukocyte antigen-E (HLA-E) is a non-classical HLA class I gene that shows
      a limited degree of polymorphism compared to the classical HLA genes. The HLA-E
      molecule can bind peptides derived from the leader sequence of various HLA class
      I alleles and some viral homologues, including CMV. The HLA-E peptide complex can
      act as a ligand for the CD94/NKG2 receptors expressed on the surface of natural
      killer cells and T cell subsets. Differences in expression levels between the
      different HLA-E alleles have been reported and a role for HLA-E polymorphism in
      stem cell transplantation has been postulated. This chapter focuses on routine
      technologies for HLA-E typing: the sequence-specific primer-PCR method that uses
      sequence-specific primers, the PCR sequence-specific oligonucleotides Luminex
      method, using sequence-specific probes attached to beads and the sequencing-based
      typing method, where sequencing of the alleles is performed.

PMID- 22665233
TI  - Molecular analysis of complement component C4 gene copy number.
AB  - Classical, alternative, or lectin pathways may activate the complement system
      cascade. The classical pathway includes the C4 protein and functions in the
      prevention of immune complex precipitation and in clearance of immune
      complexes.Two isotypes of C4-C4A and C4B-are coded by genes located at two loci
      within the major histocompatibility complex (MHC) on chromosome 6. While these
      isotypes share over 99% amino acid sequence homology, five nucleotide differences
      located in exon 26 are responsible for major structural and functional
      differences between the C4 isotypes.C4A and C4B are highly polymorphic with over
      40 alleles, gene duplications, and "null alleles". C4 genes may be short (14.6
      kb) or long (21 kb), due to the absence or presence of an endogenous retroviral
      sequence-HERV-K(C4)-in intron 9, respectively. The C4 gene copy number (GCN) can
      vary from 1-3 per haplotype or 2-6 per diploid genome. The variation in GCN leads
      to a range of C4 plasma protein concentrations among healthy subjects. In
      subjects with equal numbers of C4 genes, subjects with short genes have C4 plasma
      levels relatively higher than subjects with long genes.Variation of the C4 GCN,
      the gene size (long or short) and the C4 isotypes (C4A and C4B) may also lead to
      susceptibility to autoimmune disease. Therefore, in subjects with autoimmune
      disease, a low serum C4 level may be due to ongoing disease activity associated
      with complement activation and consumption or it may be due to genetic factors.
      Distinguishing between these will have clinical implications.Exact determination
      of GCN can be difficult, at least in part due to the high degree of homology
      between C4A and C4B and a variety of techniques has been described. This chapter
      describes a quantitative TaqMan real-time PCR (qPCR) copy number assay, based on
      our laboratory experience using this assay.

PMID- 22665234
TI  - Genotyping of single nucleotide polymorphisms by 5' nuclease allelic
      discrimination.
AB  - Real-time quantitative PCR is an efficient method for high-throughput genotyping
      of single nucleotide polymorphisms (SNPs). In this chapter, we describe the 5'
      nuclease allelic discrimination assay for genotyping biallelic SNPs.

PMID- 22665235
TI  - High resolution MICA genotyping by sequence-based typing (SBT).
AB  - We have developed a MICA typing method based on polymerase chain reaction (PCR)
      sequence-based typing and a computer program that determines the polymorphisms
      and distinguishes the GCT repeats in exon 5. One PCR amplification was performed
      to obtain templates of 2.2 kb, including exons 2, 3, 4, and 5 of MICA to be
      sequenced with two forward and two reverse primers. Overlay of nucleotide
      sequencing signals resulting from presence of different GCT repeats in exon 5
      from two different MICA alleles can be identified by a computer program that
      analyses the combined signal string containing the 35 bases.

PMID- 22665236
TI  - Standard methods for the management of immunogenetic data.
AB  - In this chapter, we outline some basic principles for the consistent management
      of immunogenetic data. These include the preparation of a single master data file
      that can serve as the basis for all subsequent analyses, a focus on the quality
      and homogeneity of the data to be analyzed, the documentation of the coding
      systems used to represent the data, and the application of nomenclature standards
      specific for each immunogenetic system being evaluated. The data management
      principles discussed here are intended to provide a foundation for the data
      analysis methods detailed in Chaps. 13 and 14 . The relationship between the data
      management and analysis methods covered in these three chapters is illustrated in
      Fig. 3.The application of these data management principles is a first step toward
      consistent and reproducible data analyses. While it may take extra time and
      effort to apply them, we feel that it is better to take this approach than to
      assume that low data quality can be compensated for by large sample sizes.In
      addition to their relevance for analytical reproducibility, it is important to
      consider these data management principles from an ethical perspective. The
      reliability of the data collected and generated as part of a research study
      should be as important a component of the ethical review of a research
      application as the security of those data. Finally, in addition to ensuring the
      integrity of the data from collection to publication, the application of these
      data management principles will provide a means to foster research integrity and
      to improve the potential for collaborative data sharing.

PMID- 22665239
TI  - Impact of HLA matching and HLA antibodies in organ transplantation: a
      collaborative transplant study view.
AB  - The Collaborative Transplant Study (CTS) was initiated in 1982 in Heidelberg,
      Germany, and originated from the need to gain further insight into the complex
      problems and risks involved in human organ transplantation. Currently, more than
      400 transplant centers in 45 countries are contributing to this voluntary
      international effort, and from the beginning of the study, the impact on graft
      outcome of immunological factors, such as matching for HLA antigens and
      allosensitization to HLA and non-HLA antigens, have been areas of interest.
      Herein, we summarize the recent findings from the CTS on these two topics.

PMID- 22665237
TI  - Analytical methods for immunogenetic population data.
AB  - In this chapter, we describe analyses commonly applied to immunogenetic
      population data, along with software tools that are currently available to
      perform those analyses. Where possible, we focus on tools that have been
      developed specifically for the analysis of highly polymorphic immunogenetic data.
      These analytical methods serve both as a means to examine the appropriateness of
      a dataset for testing a specific hypothesis, as well as a means of testing
      hypotheses. Rather than treat this chapter as a protocol for analyzing any
      population dataset, each researcher and analyst should first consider their data,
      the possible analyses, and any available tools in light of the hypothesis being
      tested. The extent to which the data and analyses are appropriate to each other
      should be determined before any analyses are performed.

PMID- 22665238
TI  - Analytical methods for disease association studies with immunogenetic data.
AB  - Disease association studies involving highly polymorphic immunogenetic data may
      involve analyses at one or many units of analysis, including amino acid, allele,
      genotype and haplotype levels, as well as consideration of gene-gene or gene
      environment interactions. The selection of the appropriate statistical tests is
      critical and will be dependent on the nature of the dataset (e.g., case-control
      vs. family data) as well as the specific research hypotheses being tested. This
      paper describes the various study and analysis categories used for such analyses,
      including the advantages and limitations of such techniques.

PMID- 22665240
TI  - Screening for antibodies against MICA by Luminex flow cytometry.
AB  - Antibodies against MICA have been found in organ transplant recipients and were
      found to be associated with decreased survival of kidney allografts. The MICA
      antibody screening assay is a Luminex-based solid phase immunoassay designed to
      detect IgG antibodies binding to beads pre-coated with recombinant preparations
      of MICA alleles. These beads coated with soluble MICA recombinant proteins
      including 11 common alleles have been produced in our laboratory and similar
      preparations have been available from commercial sources. Here, we describe the
      procedure of MICA antibody screening with a prepared kit, in which all the
      reagents were optimized and standardized. We also review how to document the
      quality of single MICA antigen beads using MICA-specific monoclonal antibodies,
      as well as quality control of the procedure and data analysis.

PMID- 22665241
TI  - HLA antibody detection and characterization by solid phase immunoassays: methods
      and pitfalls.
AB  - Solid phase immunoassays for the detection and characterization of HLA-specific
      antibodies provide greatly increased sensitivity, specificity, and time and
      reagent efficiency, compared to the traditionally used cell-based methods.
      Testing is performed using commercially available test kits. The assays are of
      two general types: enzyme-linked immunosorbent assays and multianalyte bead. The
      types vary in both sensitivity and equipment requirements.While these assays
      afford great improvement over the cell-based assays, they can be confounded by
      interference from substances within the serum that result in high background
      reactivity. The high sensitivity of the assays also makes them more susceptible
      to environmental factors and operator variability. The user must be aware of the
      capabilities of the various formats, the factors that can affect test results,
      and lot to lot variability of any single product. Knowledge of the
      characteristics of each product and thorough and accurate analysis of the results
      are essential to the utility of these assays.

PMID- 22665242
TI  - Detection and characterisation of alloreactive T cells.
AB  - T cell alloreactivity is responsible for much of the morbidity and mortality
      associated with tissue transplantation and graft versus host disease.
      Immunoassays for ex vivo monitoring and quantitation of alloreactive T cells are
      being increasingly utilised to provide valuable information for individualised
      clinical management of transplant recipients. Here we describe detailed
      methodologies for both traditional and novel assays utilised for the detection,
      quantitation, and functional characterisation of alloreactive T cells and
      highlight the key advantages and disadvantages of each system.

PMID- 22665243
TI  - Detection of allo-HLA cross-reactivity by virus-specific memory T-cell clones
      using single HLA-transfected K562 cells.
AB  - The ability to directly measure virus-specific lymphocytes using fluorochrome
      labeled tetrameric complexes has proven a great advancement for the
      transplantation field. Viral peptide/HLA tetrameric complexes allow the rapid
      generation of virus-specific clones using single cell sorting apparatus,
      permitting the determination of alloreactivity from a single TCR with known
      specificity. When combined with new target "detector" cells called single HLA
      antigen-transfected K562 cells (SALs), the human alloresponse can for the first
      time be examined specifically and reliably. Here we describe a method for
      detection of "heterologous immunity" from virus-specific memory T-cells using
      single HLA expressing cell lines as allogeneic targets.

PMID- 22665244
TI  - Separation and cryopreservation of lymphocytes from spleen and lymph node.
AB  - Spleen and lymph node retrieved post-mortem from deceased organ donors are a rich
      source of lymphocytes. Storage of lymphocytes separated from these sources can be
      valuable where post-transplant testing (crossmatching) is required. DNA
      extraction from stored lymphocytes also allows further genetic testing where
      required, for example additional HLA typing not performed at the time of
      transplant for donor-specific antibody monitoring. Methods for the isolation and
      freezing of such cells is described.

PMID- 22665245
TI  - Crossmatching by complement-dependent lymphocytotoxicity.
AB  - The presence of preformed donor-specific HLA antibodies detected by Complement
      dependent cyto-toxicity (CDC) crossmatch assay is associated with a high
      incidence of hyperacute or accelerated rejection and remains one of the gold
      standard tests pre-transplant. The standard CDC crossmatch detects IgG1, IgG3,
      and IgM antibody, i.e. complement fixing, bound to the native viable cell surface
      of lymphocytes. The crossmatch can be enhanced with the addition of anti-human
      globulin to detect non-complement fixing antibodies (IgG2 and IgG4), and
      sensitivity can be improved with prolonged incubation times.

PMID- 22665246
TI  - The lymphocyte crossmatch by flow cytometry for kidney transplantation.
AB  - The flow cytometric lymphocyte crossmatch is a standard technique for evaluating
      the compatibility of potential kidney transplant recipients and donors. Recipient
      serum is incubated with donor lymphocytes and the latter are analysed in a flow
      cytometer for the presence of bound IgG antibodies. An increase in the level of
      IgG binding compared to a negative control indicates the presence of donor
      specific antibodies which may lead to deleterious graft function. Described here
      is a method to perform T and B lymphocyte crossmatching in the same tube to
      detect IgG donor-reactive antibodies.

PMID- 22665247
TI  - Overview of the killer cell immunoglobulin-like receptor system.
AB  - Natural killer (NK) cells are more than simple killers and have been implicated
      in control and clearance of malignant and virally infected cells, regulation of
      adaptive immune responses, rejection of bone marrow transplants, and autoimmunity
      and the maintenance of pregnancy. Human NK cells largely use a family of germ
      line encoded killer cell immunoglobulin-like receptors (KIR) to respond to the
      perturbations from self-HLA class I molecules present on infected, malignant, or
      HLA-disparate fetal or allogenic transplants. Genes encoding KIR receptors and
      HLA class I ligands are located on different chromosomes, and both feature
      extraordinary diversity in the number and type of genes. The independent
      segregation of KIR and HLA gene families produce diversity in the number and type
      of KIR-HLA gene combinations inherited in individuals, which may determine their
      immunity and susceptibility to diseases. This chapter provides an overview of NK
      cells and their unprecedented phenotypic and functional diversity within and
      between individuals.

PMID- 22665248
TI  - KIR typing by non-sequencing methods: polymerase-chain reaction with sequence
      specific primers.
AB  - The killer-cell immunoglobulin-like receptors (KIR), which enable NK cells to
      detect allogeneic target cells and abnormalities in the expression of self-HLA
      molecules, are encoded by genes that display extensive copy number variation.
      These variations in the KIR genotype are relevant for multiple aspects of human
      health, including therapy of cancer. PCR with sequence-specific primers (SSP) is
      simplest and most widely used among techniques for studying KIR genotypes. Here,
      we present a protocol that details the critical steps of a method for KIR
      genotyping by PCR-SSP.

PMID- 22665249
TI  - Killer cell immunoglobulin-like receptors (KIR) typing by DNA sequencing.
AB  - DNA sequencing is a powerful technique for identifying allelic variation within
      the natural killer cell immunoglobulin-like receptor genes. Because of the
      relatively large size of the KIR genes, each locus is amplified in two or more
      overlapping segments. Sanger sequencing of each gene from a preparation
      containing one or two alleles yields a sequence that is used to identify the
      alleles by comparison with a reference database.

PMID- 22665250
TI  - An overview of methods required to evaluate donor NK cell alloreactivity for
      haploidentical haemopoietic stem cell transplantation.
AB  - Donor-vs.-recipient NK cell alloreactivity has been established as a key
      therapeutic element in HLA haplotypemismatched hematopoietic transplants in acute
      myeloid leukemia. NK cell allotherapy for leukemia is deployed through stem cell
      transplantation and ensuing NK cell reconstitution across KIR ligand mismatches.
      It is effected by functional NK cells which express inhibitory killer cell
      immunoglobulin-like receptor(s) (KIRs) for self-class I ligand(s), sense missing
      expression of donor KIR ligand(s) in the recipient, and mediate alloreactions.
      Donor-vs.-recipient NK cell alloreactivity is evaluated by integrating genetic,
      phenotypic, and functional features.

PMID- 22665251
TI  - The detection of NK cell alloreactivity by flow cytometric CD107a assay.
AB  - Natural killer (NK) cell alloreactivity can be exploited in haploidentical (one
      haplotype mismatched) haematopoietic stem cell transplantation (HSCT) to prevent
      leukaemia relapse, rejection, and graft-vs-host disease (GVHD) (Blood 94:333-339;
      Science 295:2097-2100). If NK cell alloreactivity is to be exploited in HSCT, it
      is important to be able to reliably select donors who have NK alloreactivity
      towards the patient. The detection of donor NK alloreactivity towards patient
      target cells has traditionally been evaluated by NK cell cloning and (51)Cr
      release cytotoxicity assay. This approach is complex and time consuming with
      results taking up to 6 weeks. Here, we detail a novel flow cytometric CD107a
      based assay capable of detecting NK cell alloreactivity in 14 days.

PMID- 22665252
TI  - Clinical production and therapeutic applications of alloreactive natural killer
      cells.
AB  - Recent advances have improved our understanding of natural killer (NK) cell
      mediated alloreactivity after hematopoietic cell transplantation (HCT) or with
      adoptive transfer. NK cells contribute to a graft-versus-leukemia effect and may
      play a role in preventing graft-versus-host disease or controlling infectious
      diseases after allogeneic HCT. New discoveries in NK cell biology, including
      characterization of NK cell receptors and their interactions with self-HLA
      molecules and a better understanding of the mechanism of NK cell education have
      led to the development of novel strategies to exploit NK cell alloreactivity
      against tumors. While early studies using autologous NK cells lacked efficacy,
      the use of adoptively transferred NK cells to treat hematopoietic malignancies
      has been expanding. The production of allogeneic donor NK cells requires
      efficient removal of T- and B cells from clinical-scale leukapheresis
      collections. The goal of this chapter is to review NK cell biology, NK cell
      receptors, the use of NK cells as therapy and then to discuss the clinical
      decisions resulting in our current good manufacturing practices processing and
      activation of human NK cells for therapeutic use.

PMID- 22665253
TI  - Minor histocompatibility antigen typing by DNA sequencing for clinical practice
      in hematopoietic stem-cell transplantation.
AB  - In HLA-matched stem-cell transplantation (SCT), minor H antigens are key
      molecules driving allo-immune responses in both graft-versus-host disease (GvHD)
      and in graft-versus-leukemia (GvL) reactivity. Dissection of the dual function of
      minor H antigens became evident through their different modes of tissue and cell
      expression, i.e., hematopoietic system restricted or broad. Broadly expressed
      minor H antigens are the targets of immune responses in both arms of graft-versus
      host (GvH) responses, i.e., both GvHD and GvL, whereas the immune responses
      against the hematopoietic system-specific minor H antigens are restricted to the
      GvL arm of SCT. Evidently, it is this latter group of minor H antigens that can
      function as curative tools for stem-cell (SC)-based immunotherapy of
      hematological malignancies and disorders. The HLA-matched patient/donor
      combinations, incompatible for one of the hematopoietic-specific minor H
      antigens, are suitable for minor H antigen immunotherapy (Goulmy, Immunol Rev
      157:125-140, 1997). Information on the minor H antigen phenotype is therefore
      needed. Hereto, genomic typing for minor H antigens has been implemented in many
      HLA laboratories. Here, we firstly summarize the relevance of minor H antigens
      particularly in hematopoietic SCT. Secondly, we describe a method for typing the
      various polymorphic minor H antigens molecularly identified to date by DNA
      sequencing.

PMID- 22665254
TI  - Donor registries and search strategies.
AB  - The optimal donor of hematopoietic progenitor cells shares alleles of the major
      histocompatibility genes with the recipient. This chapter describes the
      strategies aimed at identifying such a matched donor from registries of
      volunteers or from umbilical cord blood banks.

PMID- 22665255
TI  - Cytokine gene polymorphisms: methods of detection and biological significance.
AB  - In recent years, several functional polymorphisms, particularly, SNPs have been
      identified in cytokines and their receptor genes that regulate levels of cytokine
      expression. These have been implicated as immune prognostic markers in diseases,
      including differential response to therapy and as biomarkers of graft outcome
      following organ and stem cell transplantation. Population distribution of
      cytokine gene polymorphisms (CGPs) reveals significant variations in allele
      frequencies in different ethnic groups and this might explain, to some extent,
      the observed differences in SNP associations with various diseases and immune
      pathologies. A number of molecular methods are available for defining CGPs. These
      include PCR-SSP, AFLP, Taqman probe assays as well as sequencing based typing. Of
      these, the PCR-based sequence-specific primer based test is the most widely
      accepted technique. This chapter describes steps involved in this procedure along
      with sources for procuring essential reagents. An important aspect of CGP
      analyses is the correct interpretation of results particularly determination of
      their multilocus haplotypes.

PMID- 22665256
TI  - IMGT((r)) tools for the nucleotide analysis of immunoglobulin (IG) and T cell
      receptor (TR) V-(D)-J repertoires, polymorphisms, and IG mutations: IMGT/V-QUEST
      and IMGT/HighV-QUEST for NGS.
AB  - IMGT/V-QUEST is the highly customized and integrated online IMGT((r)) tool for
      the standardized analysis of the immunoglobulin (IG) or antibody and T cell
      receptor (TR) rearranged nucleotide sequences. The analysis of these antigen
      receptors represents a crucial challenge for the study of the adaptive immune
      response in normal and disease-related situations. The expressed IG and TR
      repertoires represent a potential of 10(12) IG and 10(12) TR per individual. This
      huge diversity results from mechanisms that occur at the DNA level during the IG
      and TR molecular synthesis. These mechanisms include the combinatorial
      rearrangements of the variable (V), diversity (D) and joining (J) genes, the N
      diversity (deletion and addition at random of nucleotides during the V-(D)-J
      rearrangement) and, for IG, somatic hypermutations. IMGT/V-QUEST identifies the
      V, D, J genes and alleles by alignment with the germline IG and TR gene and
      allele sequences of the IMGT reference directory. The tool describes the V-REGION
      mutations and identifies the hot spot positions in the closest germline V gene.
      IMGT/V-QUEST integrates IMGT/JunctionAnalysis for a detailed analysis of the V-J
      and V-D-J junctions and IMGT/Automat for a complete annotation of the sequences
      and also provides IMGT Collier de Perles. IMGT/HighV-QUEST, the high-throughput
      version of IMGT/V-QUEST, implemented to answer the needs of deep sequencing data
      analysis from Next Generation Sequencing (NGS), allows the analysis of thousands
      of IG and TR sequences in a single run. IMGT/V-QUEST and IMGT/HighV-QUEST are
      available at the IMGT((r)) Home page, http://www.imgt.org.

PMID- 22665257
TI  - IMGT/DomainGapAlign: the IMGT(r) tool for the analysis of IG, TR, MH, IgSF, and
      MhSF domain amino acid polymorphism.
AB  - IMGT/DomainGapAlign is the online tool of IMGT((r)), the international
      ImMunoGeneTics information system((r)), for the analysis of amino acid sequences
      and two-dimensional (2D) structures of domains. IMGT/DomainGapAlign allows the
      analysis of the closest variable (V) and constant (C) domains of immunoglobulins
      (IG) or antibodies, T cell receptors (TR), and immunoglobulin superfamily (IgSF)
      proteins, and of the groove (G) domains of major histocompatibility (MH; in
      humans, HLA for human leukocyte antigen) and MH superfamily proteins.
      IMGT/DomainGapAlign aligns the user own sequences against the IMGT domain
      reference directory, displays amino acid changes, creates IMGT gaps, and delimits
      the domain strands and loops (and helix for G domain) according to the IMGT
      unique numbering. IMGT/DomainGapAlign is coupled to the IMGT/Collier-de-Perles
      tool that draws standardized IMGT Colliers de Perles. The analysis is based on
      the IMGT-ONTOLOGY concepts of identification, classification, description, and
      numerotation generated from the axioms of the Formal IMGT-ONTOLOGY or IMGT
      Kaleidoscope. IMGT/DomainGapAlign provides an invaluable help for antibody
      engineering and antibody humanization as it precisely defines the standardized
      framework regions (FR-IMGT) and complementarity determining regions (CDR-IMGT) to
      be grafted. IMGT/DomainGapAlign is freely available at http://www.imgt.org.

PMID- 22665258
TI  - Human Gm, Km, and Am allotypes and their molecular characterization: a remarkable
      demonstration of polymorphism.
AB  - Human immunoglobulin allotypes are antigenic determinants (or "markers")
      determined serologically, classically by hemagglutination inhibition, on the
      human immunoglobulin (IG) heavy and light chains. The allotypes have been
      identified on the gamma1, gamma2, gamma3, and alpha2 heavy chains (they are
      designated as G1m, G2m, G3m, and A2m allotypes, respectively), and on the kappa
      light chain (Km allotypes). Gm-Am allotypes are inherited in fixed combinations,
      or Gm-Am haplotypes, owing to the linkage of the human IGHC genes (IGHG3, IGHG1,
      IGHA1, IGHG2, IGHG4, IGHE, and IGHA2 from 5' to 3' in the IGH locus on chromosome
      14). Gm and Am allotypes have been one of the most powerful tools in population
      genetics and very instrumental in molecular characterization of the human IGHC
      genes (gene conversion, copy number variation, gene order). They represent a
      major system for understanding immunogenicity of the polymorphic IG chains, in
      relation with amino acid and conformational changes. The correlation between G3m
      allotypes and amino acid changes has been possible with the sequencing of many
      alleles of the IGHG3 gene, from individuals from different populations and with
      known allotypes. In this chapter, we integrate genetics and sequence data and
      provide an updated overview of the Gm-Am haplotypes and Km allotypes. We propose,
      for the first time, a complete elucidation of the G3m allotypes, illustrated by
      the "IMGT G3m allele butterfly" concept that allows a graphical representation of
      the G3m alleles (variants of a gene expressing a given set of allotypes).
      Knowledge of allotypes is important in antibody engineering and humanization of
      monoclonal antibodies to improve immunotherapy.

PMID- 22665259
TI  - The psychiatric vulnerability gene CACNA1C and its sex-specific relationship with
      personality traits, resilience factors and depressive symptoms in the general
      population.
AB  - Genome-wide association studies have reported an association between the A-allele
      of rs1006737 within CACNA1C and affective disorders and schizophrenia. The aim of
      the present study was to investigate the relationship between rs1006737 and
      established and potential endophenotypes for these disorders in a population
      based cohort of 3793 subjects, using an analytical method designed to assess a
      previously reported sex-specific effect of CACNA1C. The investigated
      endophenotypes included personality traits and resilience factors. At 10-year
      follow-up, subjects were screened for depressive symptoms. All subjects were
      genotyped for rs1006737. The direction of the effect and mode of inheritance of
      rs1006737 differed between the sexes. In men, the A-allele was associated with
      higher emotional lability and lower resilience, that is, lower sense of coherence
      (P=0.021), lower perceived social support (P=0.018), lower dispositional optimism
      (P=0.032) and more depressive symptoms at follow-up (P=0.007). In women, the A
      allele was associated with lower emotional lability and stronger resilience, that
      is, higher sense of coherence (P=0.00028), higher perceived social support
      (P=0.010), lower neuroticism (P=0.022) and fewer depressive symptoms at follow-up
      (P=0.035). After conservative Bonferroni correction for 32 tests, results only
      remained significant for sense of coherence in women (P=0.009). These results
      suggest that CACNA1C is involved in the genetic architecture of endophenotypes
      for affective disorders and schizophrenia, and that it shows a distinct sex
      specific effect. Comprehensive phenotype characterization in case-control samples
      and the general population, as well as an adequate modeling of sex-specific
      genetic effects, may be warranted to elucidate the pathogenetic mechanisms
      conferred by robustly identified susceptibility genes.

PMID- 22665260
TI  - Involvement of estrogen receptor beta in maintenance of serotonergic neurons of
      the dorsal raphe.
AB  - The serotonergic neurons of the dorsal raphe (DR) nucleus in the CNS are involved
      in fear, anxiety and depression. Depression and anxiety occur quite frequently in
      postmenopausal women, but estrogen replacement to correct these CNS disorders is
      at present not favored because estrogen carries with it an increased risk for
      breast cancer. Serotonin synthesis, release and reuptake in the DR are targets of
      pharmaceuticals in the treatment of depression. In the present study we have
      examined by immunohistochemistry, the expression of two nuclear receptors, that
      is, the estrogen receptors ERalpha and ERbeta. We found that ERbeta but not
      ERalpha is strongly expressed in the DR and there is no sex difference and no
      change with ageing in the number of tryptophan hydroxylase (TPH)-positive neurons
      in the DR of wild-type (WT) mice. However, in ovariectomized (OVX) WT and in
      ERbeta(-/-) mice, there was a marked reduction in the number of TPH-positive
      normal-looking neurons and a marked increase in TPH-positive spindle-shaped
      cells. These neuronal changes were prevented in mice 1-3 weeks (but not 10 weeks)
      after OVX by the selective ERbeta agonist, LY3201, given as continuous release
      pellets for 3 days. The ERbeta agonist had no effects on glucose homeostasis.
      Thus, the onset of action of the ERbeta agonist is rapid but there is a limited
      window in time after estrogen loss when the drug is useful. We conclude that,
      rather than estradiol, ERbeta agonists could be useful pharmaceuticals in
      maintaining functional DR neurons to treat postmenopausal depression.

PMID- 22665261
TI  - Cortical thickness of superior frontal cortex predicts impulsiveness and
      perceptual reasoning in adolescence.
AB  - Impulsiveness is a pivotal personality trait representing a core domain in all
      major personality inventories. Recently, impulsiveness has been identified as an
      important modulator of cognitive processing, particularly in tasks that require
      the processing of large amounts of information. Although brain imaging studies
      have implicated the prefrontal cortex to be a common underlying representation of
      impulsiveness and related cognitive functioning, to date a fine-grain and
      detailed morphometric analysis has not been carried out. On the basis of ahigh
      resolution magnetic resonance scans acquired in 1620 healthy adolescents
      (IMAGEN), the individual cortical thickness (CT) was estimated. Correlations
      between Cloninger's impulsiveness and CT were studied in an entire cortex
      analysis. The cluster identified was tested for associations with performance in
      perceptual reasoning tasks of the Wechsler Intelligence Scale for Children (WISC
      IV). We observed a significant inverse correlation between trait impulsiveness
      and CT of the left superior frontal cortex (SFC; Monte Carlo Simulation P<0.01).
      CT within this cluster correlated with perceptual reasoning scores (Bonferroni
      corrected) of the WISC IV. On the basis of a large sample of adolescents, we
      identified an extended area in the SFC as a correlate of impulsiveness, which
      appears to be in line with the trait character of this prominent personality
      facet. The association of SFC thickness with perceptual reasoning argues for a
      common neurobiological basis of personality and specific cognitive domains
      comprising attention, spatial reasoning and response selection. The results may
      facilitate the understanding of the role of impulsiveness in several psychiatric
      disorders associated with prefrontal dysfunctions and cognitive deficits.

PMID- 22665262
TI  - Forebrain elimination of cacna1c mediates anxiety-like behavior in mice.

PMID- 22665263
TI  - Molecular genetics of obsessive-compulsive disorder: a comprehensive meta
      analysis of genetic association studies.
AB  - Twin studies indicate that obsessive-compulsive disorder (OCD) is strongly
      influenced by additive genetic factors. Yet, molecular genetic association
      studies have yielded inconsistent results, possibly because of differences across
      studies in statistical power. Meta-analysis can yield greater power. This study
      reports the first comprehensive meta-analysis of the relationship between OCD and
      all previously examined polymorphisms for which there was sufficient information
      in the source studies to compute odds ratios (ORs). A total of 230 polymorphisms
      from 113 genetic association studies were identified. A full meta-analysis was
      conducted for 20 polymorphisms that were examined in 5 or more data sets, and a
      secondary meta-analysis (limited to the computation of mean effect sizes) was
      conducted for 210 polymorphisms that were examined in fewer than 5 data sets. In
      the main meta-analysis, OCD was associated with serotonin-related polymorphisms
      (5-HTTLPR and HTR2A) and, in males only, with polymorphisms involved in
      catecholamine modulation (COMT and MAOA). Nonsignificant trends were identified
      for two dopamine-related polymorphisms (DAT1 and DRD3) and a glutamate-related
      polymorphism (rs3087879). The secondary meta-analysis identified another 18
      polymorphisms with significant ORs that merit further investigation. This study
      demonstrates that OCD is associated with multiple genes, with most having a
      modest association with OCD. This suggests a polygenic model of OCD, consistent
      with twin studies, in which multiple genes make small, incremental contributions
      to the risk of developing the disorder. Future studies, with sufficient power to
      detect small effects, are needed to investigate the genetic basis of OCD
      subtypes, such as early vs late onset OCD. 

PMID- 22665264
TI  - Measuring endogenous changes in serotonergic neurotransmission in humans: a
      [11C]CUMI-101 PET challenge study.
AB  - Serotonin (5-HT) neurotransmission is implicated in cognitive and emotional
      processes and a number of neuropsychiatric disorders. The use of positron
      emission tomography (PET) to measure ligand displacement has allowed estimation
      of endogenous dopamine release in the human brain; however, applying this
      methodology to assess central 5-HT release has proved more challenging. The aim
      of this study was to assess the sensitivity of a highly selective 5-HT(1A)
      partial agonist radioligand [(11)C]CUMI-101 to changes in endogenous 5-HT levels
      induced by an intravenous challenge with the selective 5-HT re-uptake inhibitor
      (SSRI), citalopram, in healthy human participants. We studied 15 healthy
      participants who underwent PET scanning in conjunction with [(11)C]CUMI-101 after
      receiving an intravenous infusion of citalopram 10 mg or placebo in a double
      blind, crossover, randomized design. Regional estimates of binding potential
      (BP(ND)) were obtained by calculating total volumes of distribution (V(T)) for
      presynaptic dorsal raphe nucleus (DRN) and postsynaptic cortical regions.
      Relative to placebo, citalopram infusion significantly increased [(11)C]CUMI-101
      BP(ND) at postsynaptic 5-HT(1A) receptors in several cortical regions, but there
      was no change in binding at 5-HT(1A) autoreceptors in the DRN. Across the
      postsynaptic brain regions, citalopram treatment induced a mean 7% in [(11)C]CUMI
      101 BP(ND) (placebo 1.3 (0.2); citalopram 1.4 (0.2); paired t-test P=0.003). The
      observed increase in postsynaptic [(11)C]CUMI-101 availability identified
      following acute citalopram administration could be attributable to a decrease in
      endogenous 5-HT availability in cortical terminal regions, consistent with
      preclinical animal studies, in which acute administration of SSRIs decreases DRN
      cell firing through activation of 5-HT(1A) autoreceptors to reduce 5-HT levels in
      postsynaptic regions. We conclude that [(11)C]CUMI-101 may be sensitive to
      changes in endogenous 5-HT release in humans.

PMID- 22665265
TI  - Uncoupling of PI3K from ErbB3 impairs mammary gland development but does not
      impact on ErbB2-induced mammary tumorigenesis.
AB  - The formation of ErbB2/ErbB3 heterodimers plays a critical role in ErbB2-mediated
      signaling in both normal mammary development and mammary tumor progression.
      Through 7 phosphoinositide 3-kinase (PI3K) phosphotyrosine-binding sites, ErbB3
      is able to recruit PI3K and initiate the PI3K/AKT signaling pathway. To directly
      explore the importance of the ErbB3/PI3K pathway in mammary development and
      tumorigenesis, we generated a mouse model that carries a mutant ErbB3 allele
      lacking the seven known PI3K-binding sites (ErbB3(Delta85)). Mice homozygous for
      the ErbB3(Delta85) allele exhibited an initial early growth defect and a dramatic
      impairment of mammary epithelial outgrowth. Although homozygous adult mice
      eventually recovered from the growth defect, their mammary glands continued to
      manifest the mammary outgrowth and lactation defects throughout their adult life.
      Interestingly, despite the presence of a profound mammary gland defect, all of
      the female ErbB3Delta85 mice developed metastatic ErbB2-induced mammary tumors
      secondary to mammary epithelial expression of an activated ErbB2 oncogene capable
      of compensatory PI3K signaling from both EGF receptor and ErbB2. Our findings
      therefore indicate that, although ErbB3-associated PI3K activity is critical for
      mammary development, it is dispensable for ErbB2-induced mammary tumor
      progression.

PMID- 22665266
TI  - A zebrafish model to study and therapeutically manipulate hypoxia signaling in
      tumorigenesis.
AB  - Hypoxic signaling is a central modulator of cellular physiology in cancer. Core
      members of oxygen-sensing pathway including the von Hippel-Lindau tumor
      suppressor protein (pVHL) and the hypoxia inducible factor (HIF) transcription
      factors have been intensively studied, but improved organismal models might speed
      advances for both pathobiologic understanding and therapeutic modulation. To
      study HIF signaling during tumorigenesis and development in zebrafish, we
      developed a unique in vivo reporter for hypoxia, expressing EGFP driven by prolyl
      hydroxylase 3 (phd3) promoter/regulatory elements. Modulation of HIF pathway in
      Tg(phd3::EGFP) embryos showed a specific role for hypoxic signaling in the
      transgene activation. Zebrafish vhl mutants display a systemic hypoxia response,
      reflected by strong and ubiquitous transgene expression. In contrast to human VHL
      patients, heterozygous Vhl mice and vhl zebrafish are not predisposed to cancer.
      However, upon exposure to dimethylbenzanthracene (DMBA), the vhl heterozygous
      fish showed an increase in the occurrence of hepatic and intestinal tumors, a
      subset of which exhibited strong transgene expression, suggesting loss of Vhl
      function in these tumor cells. Compared with control fish, DMBA-treated vhl
      heterozygous fish also showed an increase in proliferating cell nuclear antigen
      positive renal tubules. Taken together, our findings establish Vhl as a genuine
      tumor suppressor in zebrafish and offer this model as a tool to noninvasively
      study VHL and HIF signaling during tumorigenesis and development.

PMID- 22665268
TI  - Fibulin-3 promotes glioma growth and resistance through a novel paracrine
      regulation of Notch signaling.
AB  - Malignant gliomas are highly invasive and chemoresistant brain tumors with
      extremely poor prognosis. Targeting of the soluble factors that trigger invasion
      and resistance, therefore, could have a significant impact against the
      infiltrative glioma cells that are a major source of recurrence. Fibulin-3 is a
      matrix protein that is absent in normal brain but upregulated in gliomas and
      promotes tumor invasion by unknown mechanisms. Here, we show that fibulin-3 is a
      novel soluble activator of Notch signaling that antagonizes DLL3, an autocrine
      inhibitor or Notch, and promotes tumor cell survival and invasion in a Notch
      dependent manner. Using a strategy for inducible knockdown, we found that
      controlled downregulation of fibulin-3 reduced Notch signaling and led to
      increased apoptosis, reduced self-renewal of glioblastoma-initiating cells, and
      impaired growth and dispersion of intracranial tumors. In addition, fibulin-3
      expression correlated with expression levels of Notch-dependent genes and was a
      marker of Notch activation in patient-derived glioma samples. These findings
      underscore a major role for the tumor extracellular matrix in regulating glioma
      invasion and resistance to apoptosis via activation of the key Notch pathway.
      More importantly, this work describes a noncanonical, soluble activator of Notch
      in a cancer model and shows how Notch signaling can be reduced by targeting tumor
      specific accessible molecules in the tumor microenvironment.

PMID- 22665267
TI  - Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits
      tumor cell proliferation and oncogenesis.
AB  - Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene
      family, has emerging roles in cancer. We report here that NAC1 acts as a negative
      regulator of cellular senescence in transformed and nontransformed cells, and
      dysfunction of NAC1 induces senescence and inhibits its oncogenic potential. We
      show that NAC1 deficiency markedly activates senescence and inhibits
      proliferation in tumor cells treated with sublethal doses of gamma-irradiation.
      In mouse embryonic fibroblasts from NAC1 knockout mice, following infection with
      a Ras virus, NAC1-/- cells undergo significantly more senescence and are either
      nontransformed or less transformed in vitro and less tumorigenic in vivo when
      compared with NAC1+/+ cells. Furthermore, we show that the NAC1-caused senescence
      blunting is mediated by DeltaNp63, which exerts its effect on senescence through
      p21, and that NAC1 activates transcription of DeltaNp63 under stressful
      conditions. Our results not only reveal a previously unrecognized function of
      NAC1, the molecular pathway involved and its impact on pathogenesis of tumor
      initiation and development, but also identify a novel senescence regulator that
      may be exploited as a potential target for cancer prevention and treatment.

PMID- 22665269
TI  - Isolation and characterization of a novel noncoding RNA from nickel-induced lung
      cancer.
AB  - Noncoding RNAs have drawn significant attention in carcinogenesis. In this study,
      we identified a novel gene named nickel-related gene1 (NRG1) associated with
      nickel-induced cancer. By using rapid amplification of cDNA end PCR, we obtained
      the full length of the cDNA. The sequence was analyzed by using related
      bioinformatics software and comparative genomics methods. The results showed that
      NRG1 was located on chromosome 2q12, within intron2 of ADAMTS6, a disintegrin and
      metalloproteinase with thrombospondin motifs. And, NRG1 had a high level of
      homology (76 %) to rat LINE1 sequence RL1.3 (long interspersed middle repetitive
      DNA). What's more, there was no continuous open reading frame present in NRG1
      sequence. Taken together, these data demonstrate that NRG1 is a novel noncoding
      RNA, and we predicted it may be a transposon-like gene. The identification of
      NRG1 emphasized the potential role of noncoding RNA in nickel carcinogenesis.

PMID- 22665270
TI  - A detailed mammosphere assay protocol for the quantification of breast stem cell
      activity.
AB  - Since the discovery that neural tissue contains a population of stem cells that
      form neurospheres in vitro, sphere-forming assays have been adapted for use with
      a number of different tissue types for the quantification of stem cell activity
      and self-renewal. One tissue type widely used for stem cell investigations is
      mammary tissue, and the mammosphere assay has been used in both normal tissue and
      cancer. Although it is a relatively simple assay to learn, it can be difficult to
      master. There are methodological and analytical aspects to the assay which
      require careful consideration when interpreting the results. We describe here a
      detailed mammosphere assay protocol for the assessment of stem cell activity and
      self-renewal, and discuss how data generated by the assay can be analysed and
      interpreted.

PMID- 22665272
TI  - Sampling in landscape genomics.
AB  - Landscape genomics, based on the sampling of individuals genotyped for a large
      number of markers, may lead to the identification of regions of the genome
      correlated to selection pressures caused by the environment. In this chapter, we
      discuss sampling strategies to be used in a landscape genomics approach. We
      suggest that designs based on model-based stratification using the climatic
      and/or biological spaces are in general more efficient than designs based on the
      geographic space. More work is needed to identify designs that allow
      disentangling environmental selection pressures versus other processes such as
      range expansions or hierarchical population structure.

PMID- 22665273
TI  - OligoTag: a program for designing sets of tags for next-generation sequencing of
      multiplexed samples.
AB  - Next-generation sequencing systems allow high-throughput production of DNA
      sequence data. But this technology is more adapted for analyzing a small number
      of samples needing a huge amount of sequences rather than a large number of
      samples needing a small number of sequences. One solution to this problem is
      sample multiplexing. To achieve this, one can add a small tag at the extremities
      of the sequenced DNA molecules. These tags will be identified using
      bioinformatics tools after the sequencing step to sort sequences among samples.
      The rules to apply for selecting a good set of tags adapted to each situation are
      described in this chapter. Depending on the number of samples to tag and on the
      required quality of assignation, different solutions are possible. The software
      oligoTag, a part of OBITools that computes these sets of tags, is presented with
      some example sets of tags.

PMID- 22665271
TI  - Use of mechanistic modeling to assess interindividual variability and
      interspecies differences in active uptake in human and rat hepatocytes.
AB  - Interindividual variability in activity of uptake transporters is evident in
      vivo, yet limited data exist in vitro, confounding in vitro-in vivo
      extrapolation. The uptake kinetics of seven organic anion-transporting
      polypeptide substrates was investigated over a concentration range in plated
      cryopreserved human hepatocytes. Active uptake clearance (CL(active, u)),
      bidirectional passive diffusion (P(diff)), intracellular binding, and metabolism
      were estimated for bosentan, pitavastatin, pravastatin, repaglinide,
      rosuvastatin, telmisartan, and valsartan in HU4122 donor using a mechanistic two
      compartment model in Matlab. Full uptake kinetics of rosuvastatin and repaglinide
      were also characterized in two additional donors, whereas for the remaining drugs
      CL(active, u) was estimated at a single concentration. The unbound affinity
      constant (K(m, u)) and P(diff) values were consistent across donors, whereas
      V(max) was on average up to 2.8-fold greater in donor HU4122. Consistency in K(m,
      u) values allowed extrapolation of single concentration uptake activity data and
      assessment of interindividual variability in CL(active) across donors. The
      maximal contribution of active transport to total uptake differed among donors,
      for example, 85 to 96% and 68 to 87% for rosuvastatin and repaglinide,
      respectively; however, in all cases the active process was the major contributor.
      In vitro-in vivo extrapolation indicated a general underprediction of hepatic
      intrinsic clearance, an average empirical scaling factor of 17.1 was estimated on
      the basis of seven drugs investigated in three hepatocyte donors, and donor
      specific differences in empirical factors are discussed. Uptake K(m, u) and
      CL(active, u) were on average 4.3- and 7.1-fold lower in human hepatocytes
      compared with our previously published rat data. A strategy for the use of rat
      uptake data to facilitate the experimental design in human hepatocytes is
      discussed.

PMID- 22665274
TI  - SNP discovery in non-model organisms using 454 next generation sequencing.
AB  - Roche 454 sequencing of the transcriptome has become a standard approach for
      efficiently obtaining single nucleotide polymorphisms (SNPs) in non-model
      species. In this chapter, the primary issues facing the development of SNPs from
      the transcriptome in non-model species are presented: tissue and sampling
      choices, mRNA preparation, considerations of normalization, pooling and
      barcoding, how much to sequence, how to assemble the data and assess the
      assembly, calling transcriptome SNPs, developing these into genomic SNPs, and
      publishing the work. Discussion also covers the comparison of this approach to
      RAD-tag sequencing and the potential of using other sequencing platforms for SNP
      development.

PMID- 22665275
TI  - In silico fingerprinting (ISIF): a user-friendly in silico AFLP program.
AB  - The Amplified fragment Length Polymorphism (AFLP) is one of the cost-effective
      and useful fingerprinting techniques to study non-model species. One crucial AFLP
      step in the AFLP procedure is the choice of restriction enzymes and selective
      bases providing good-quality AFLP profiles. Here, we present a user-friendly
      program (ISIF) that allows carrying out in silico AFLPs on species for which
      whole genome sequences are available. Carrying out in silico analyses as
      preliminary tests can help to optimize the experimental work by allowing a rapid
      screening of candidate restriction enzymes and the combinations of selective
      bases to be used. Furthermore, using in silico AFLPs is of great interest to
      limit homoplasy and amplification of repetitive elements to target genomic
      regions of interest or to optimize complex and costly high-throughput genomic
      experiments.

PMID- 22665276
TI  - Diversity arrays technology: a generic genome profiling technology on open
      platforms.
AB  - In the last 20 years, we have observed an exponential growth of the DNA sequence
      data and simular increase in the volume of DNA polymorphism data generated by
      numerous molecular marker technologies. Most of the investment, and therefore
      progress, concentrated on human genome and genomes of selected model species.
      Diversity Arrays Technology (DArT), developed over a decade ago, was among the
      first "democratizing" genotyping technologies, as its performance was primarily
      driven by the level of DNA sequence variation in the species rather than by the
      level of financial investment. DArT also proved more robust to genome size and
      ploidy-level differences among approximately 60 organisms for which DArT was
      developed to date compared to other high-throughput genotyping technologies. The
      success of DArT in a number of organisms, including a wide range of "orphan
      crops," can be attributed to the simplicity of underlying concepts: DArT combines
      genome complexity reduction methods enriching for genic regions with a highly
      parallel assay readout on a number of "open-access" microarray platforms. The
      quantitative nature of the assay enabled a number of applications in which
      allelic frequencies can be estimated from DArT arrays. A typical DArT assay tests
      for polymorphism tens of thousands of genomic loci with the final number of
      markers reported (hundreds to thousands) reflecting the level of DNA sequence
      variation in the tested loci. Detailed DArT methods, protocols, and a range of
      their application examples as well as DArT's evolution path are presented.

PMID- 22665277
TI  - Two methods to easily obtain nucleotide sequences from AFLP loci of interest.
AB  - Genome scans based on anonymous Amplified Fragment Length Polymorphism (AFLP)
      markers scattered throughout the genome are becoming an increasingly popular
      approach to study the genetic basis of adaptation and speciation in natural
      populations. A shortcoming of this approach is that despite its efficiency to
      detect signatures of selection, it can hardly help pinpoint the specific genomic
      region(s), gene(s), or mutation(s) targeted by selection. Here, we present two
      methods to be undertaken after performing an AFLP-based genome scan to easily
      obtain the sequences of AFLP loci detected as outliers by population genomics
      approaches. The first one is based on the gel excision of the target AFLP
      fragment, after simplification of the AFLP fingerprint and separation of the
      fragments by migration. The second one is a combination of classical AFLP
      protocol and 454 pyrosequencing.

PMID- 22665278
TI  - Roche genome sequencer FLX based high-throughput sequencing of ancient DNA.
AB  - Since the development of so-called "next generation" high-throughput sequencing
      in 2005, this technology has been applied to a variety of fields. Such
      applications include disease studies, evolutionary investigations, and ancient
      DNA. Each application requires a specialized protocol to ensure that the data
      produced is optimal. Although much of the procedure can be followed directly from
      the manufacturer's protocols, the key differences lie in the library preparation
      steps. This chapter presents an optimized protocol for the sequencing of fossil
      remains and museum specimens, commonly referred to as "ancient DNA," using the
      Roche GS FLX 454 platform.

PMID- 22665279
TI  - Preparation of normalized cDNA libraries for 454 Titanium transcriptome
      sequencing.
AB  - Transcriptome sequencing from cDNA libraries has been extensively and efficiently
      used to analyze sequence variation in protein-coding genes (Expressed Sequence
      Tags) in eukaryote species. Rapid advances in next-generation sequencing (NGS)
      technology, in terms of cost, speed, and throughput, allow us to address
      previously unanswerable questions in the fields of ecology, evolution, and
      systematics using these genomic tools. Transcriptome sequencing from individuals
      across different populations and species enables researchers to study the
      evolution of gene sequence variation at a population genomics level. In this
      chapter, we describe a customized protocol that has been successfully optimized
      for the development of normalized cDNA libraries in eukaryote systems suitable
      for Roche 454 GS FLX sequencing, requiring only small quantities of starting
      material.

PMID- 22665280
TI  - RAD paired-end sequencing for local de novo assembly and SNP discovery in non
      model organisms.
AB  - Restriction-site Associated DNA (RAD) markers are rapidly becoming a standard for
      SNP discovery and genotyping studies even in organisms without a sequenced
      reference genome. It is difficult, however, to identify genes nearby RAD markers
      of interest or move from SNPs identified by RAD to a high-throughput genotyping
      assay. Paired-end sequencing of RAD fragments can alleviate these problems by
      generating a set of paired sequences that can be locally assembled into high
      quality contigs up to 1 kb in length. These contigs can then be used for SNP
      identification, homology searching, or high-throughput assay primer design. In
      this chapter, we offer suggestions on how to design a RAD paired-end (RAD-PE)
      sequencing project and the protocol for creating paired-end RAD libraries
      suitable for Illumina sequencers.

PMID- 22665281
TI  - Automated scoring of AFLPs using RawGeno v 2.0, a free R CRAN library.
AB  - Amplified Fragment Length Polymorphisms (AFLPs) are a cheap and efficient
      protocol for generating large sets of genetic markers. This technique has become
      increasingly used during the last decade in various fields of biology, including
      population genomics, phylogeography, and genome mapping. Here, we present
      RawGeno, an R library dedicated to the automated scoring of AFLPs (i.e., the
      coding of electropherogram signals into ready-to-use datasets). Our program
      includes a complete suite of tools for binning, editing, visualizing, and
      exporting results obtained from AFLP experiments. RawGeno can either be used with
      command lines and program analysis routines or through a user-friendly graphical
      user interface. We describe the whole RawGeno pipeline along with recommendations
      for (a) setting the analysis of electropherograms in combination with
      PeakScanner, a program freely distributed by Applied Biosystems; (b) performing
      quality checks; (c) defining bins and proceeding to scoring; (d) filtering
      nonoptimal bins; and (e) exporting results in different formats.

PMID- 22665282
TI  - Haplotype inference.
AB  - The information carried by combination of alleles on the same chromosome, called
      haplotypes, is of crucial interest in several fields of modern genetics as
      population genetics or association studies. However, this information is usually
      lost by sequencing and needs, therefore, to be recovered by inference. In this
      chapter, we give a brief overview on the methods able to tackle this problem and
      some practical concerns to apply them on real data.

PMID- 22665283
TI  - Allele identification in assembled genomic sequence datasets.
AB  - Allelic variation within species provides fundamental insights into the evolution
      and ecology of organisms, and information about this variation is becoming
      increasingly available in sequence datasets of multiple and/or outbred
      individuals. Unfortunately, identifying true allelic variants poses a number of
      challenges, given the presence of both sequencing errors and alleles from other
      closely related loci. We outline the key considerations involved in this process,
      including assessing the accuracy of allele resolution in sequence assembly,
      clustering of alleles within and among individuals, and identifying clusters that
      are most likely to correspond to true allelic variants of a single locus. Our
      focus is particularly on the case where alleles must be identified without a
      fully resolved reference genome, and where sequence depth information cannot be
      used to infer the putative number of loci sharing a sequence, such as in
      transcriptome or post-assembly datasets. Throughout, we provide information about
      publicly available tools to aid allele identification in such cases.

PMID- 22665284
TI  - Multiple testing in large-scale genetic studies.
AB  - Recent advances in Molecular Biology and improvements in microarray and
      sequencing technologies have led biologists toward high-throughput genomic
      studies. These studies aim at finding associations between genetic markers and a
      phenotype and involve conducting many statistical tests on these markers. Such
      Please confirm the changes in the sentence "Such a wide..." a wide investigation
      of the genome not only renders genomic studies quite attractive but also lead to
      a major shortcoming. That is, among the markers detected as associated with the
      phenotype, a nonnegligible proportion is not in reality (false-positives) and
      also true associations can be missed (false-negatives). A main cause of these
      spurious associations is due to the multiple-testing problem, inherent to
      conducting numerous statistical tests. Several approaches exist to work around
      this issue. These multiple-testing adjustments aim at defining new statistical
      confidence measures that are controlled to guarantee that the outcomes of the
      tests are pertinent.The most natural correction was introduced by Bonferroni and
      aims at controlling the family-wise error-rate (FWER) that is the probability of
      having at least one false-positive. Another approach is based on the false
      discovery-rate (FDR) and considers the proportion of significant results that are
      expected to be false-positives. Finally, the local-FDR focuses on the actual
      probability for a marker of being associated or not with the phenotype. These
      strategies are widely used but one has to be careful about when and how to apply
      them. We propose in this chapter a discussion on the multiple-testing issue and
      on the main approaches to take it into account. We aim at providing a theoretical
      and intuitive definition of these concepts along with practical advises to guide
      researchers in choosing the more appropriate multiple-testing procedure
      corresponding to the purposes of their studies.

PMID- 22665285
TI  - Population genomic analysis of model and nonmodel organisms using sequenced RAD
      tags.
AB  - The evolutionary processes of mutation, migration, genetic drift, and natural
      selection shape patterns of genetic variation among individuals, populations, and
      species, and they can do so differentially across genomes. The field of
      population genomics provides a comprehensive genome-scale view of these
      processes, even beyond traditional model organisms. Until recently, genome-wide
      studies of genetic variation have been prohibitively expensive. However, next
      generation sequencing (NGS) technologies are revolutionizing the field of
      population genomics, allowing for genetic analysis at scales not previously
      possible even in organisms for which few genomic resources presently exist. To
      speed this revolution in evolutionary genetics, we and colleagues developed
      Restriction site Associated DNA (RAD) sequencing, a method that uses Illumina NGS
      to simultaneously type and score tens to hundreds of thousands of single
      nucleotide polymorphism (SNP) markers in hundreds of individuals for minimal
      investment of resources. The core molecular protocol is described elsewhere in
      this volume, which can be modified to suit a diversity of evolutionary genetic
      questions. In this chapter, we outline the conceptual framework of population
      genomics, relate genomic patterns of variation to evolutionary processes, and
      discuss how RAD sequencing can be used to study population genomics. In addition,
      we discuss bioinformatic considerations that arise from unique aspects of NGS
      data as compared to traditional marker based approaches, and we outline some
      general analytical approaches for RAD-seq and similar data, including a
      computational pipeline that we developed called Stacks. This software can be used
      for the analysis of RAD-seq data in organisms with and without a reference
      genome. Nonetheless, the development of analytical tools remains in its infancy,
      and further work is needed to fully quantify sampling variance and biases in
      these data types. As data-gathering technology continues to advance, our ability
      to understand genomic evolution in natural populations will be limited more by
      conceptual and analytical weaknesses than by the amount of molecular data.

PMID- 22665286
TI  - Analysis and management of gene and allelic diversity in subdivided populations
      using the software program METAPOP.
AB  - METAPOP (http://webs.uvigo.es/anpefi/metapop/) is a desktop application that
      provides an analysis of gene and allelic diversity in subdivided populations from
      molecular genotype or coancestry data as well as a tool for the management of
      genetic diversity in conservation programs. A partition of gene and allelic
      diversity is made within and between subpopulations, in order to assess the
      contribution of each subpopulation to global diversity for descriptive population
      genetics or conservation purposes. In the context of management of subdivided
      populations in in situ conservation programs, the software also determines the
      optimal contributions (i.e., number of offspring) of each individual, the number
      of migrants, and the particular subpopulations involved in the exchange of
      individuals in order to maintain the largest level of gene diversity in the whole
      population with a desired control in the rate of inbreeding. The partition of
      gene and allelic diversity within and between subpopulations is illustrated with
      microsatellite and SNP data from human populations.

PMID- 22665287
TI  - DETSEL: an R-package to detect marker loci responding to selection.
AB  - In the new era of population genomics, surveys of genetic polymorphism ("genome
      scans") offer the opportunity to distinguish locus-specific from genome-wide
      effects at many loci. Identifying presumably neutral regions of the genome that
      are assumed to be influenced by genome-wide effects only, and excluding
      presumably selected regions, is therefore critical to infer population demography
      and phylogenetic history reliably. Conversely, detecting locus-specific effects
      may help identify those genes that have been, or still are, targeted by natural
      selection. The software package DETSEL has been developed to identify markers
      that show deviation from neutral expectation in pairwise comparisons of diverging
      populations. Recently, two major improvements have been made: the analysis of
      dominant markers is now supported, and the estimation of empirical P-values has
      been implemented. These features, which are described below, have been
      incorporated into an R package, which replaces the stand-alone DETSEL software
      package.

PMID- 22665288
TI  - Use of qualitative environmental and phenotypic variables in the context of
      allele distribution models: detecting signatures of selection in the genome of
      Lake Victoria cichlids.
AB  - When searching for loci possibly under selection in the genome, an alternative to
      population genetics theoretical models is to establish allele distribution models
      (ADM) for each locus to directly correlate allelic frequencies and environmental
      variables such as precipitation, temperature, or sun radiation. Such an approach
      implementing multiple logistic regression models in parallel was implemented
      within a computing program named MATSAM: . Recently, this application was
      improved in order to support qualitative environmental predictors as well as to
      permit the identification of associations between genomic variation and
      individual phenotypes, allowing the detection of loci involved in the genetic
      architecture of polymorphic characters. Here, we present the corresponding
      methodological developments and compare the results produced by software
      implementing population genetics theoretical models (DFDIST: and BAYESCAN: ) and
      ADM (MATSAM: ) in an empirical context to detect signatures of genomic divergence
      associated with speciation in Lake Victoria cichlid fishes.

PMID- 22665289
TI  - Genomic scan as a tool for assessing the genetic component of phenotypic variance
      in wild populations.
AB  - Methods for estimating quantitative trait heritability in wild populations have
      been developed in recent years which take advantage of the increased availability
      of genetic markers to reconstruct pedigrees or estimate relatedness between
      individuals, but their application to real-world data is not exempt from
      difficulties. This chapter describes a recent marker-based technique which, by
      adopting a genomic scan approach and focusing on the relationship between
      phenotypes and genotypes at the individual level, avoids the problems inherent to
      marker-based estimators of relatedness. This method allows the quantification of
      the genetic component of phenotypic variance ("degree of genetic determination"
      or "heritability in the broad sense") in wild populations and is applicable
      whenever phenotypic trait values and multilocus data for a large number of
      genetic markers (e.g., amplified fragment length polymorphisms, AFLPs) are
      simultaneously available for a sample of individuals from the same population.
      The method proceeds by first identifying those markers whose variation across
      individuals is significantly correlated with individual phenotypic differences
      ("adaptive loci"). The proportion of phenotypic variance in the sample that is
      statistically accounted for by individual differences in adaptive loci is then
      estimated by fitting a linear model to the data, with trait value as the
      dependent variable and scores of adaptive loci as independent ones. The method
      can be easily extended to accommodate quantitative or qualitative information on
      biologically relevant features of the environment experienced by each sampled
      individual, in which case estimates of the environmental and genotype *
      environment components of phenotypic variance can also be obtained.

PMID- 22665290
TI  - Important issues in planning a proteomics experiment: statistical considerations
      of quantitative proteomic data.
AB  - Mass spectrometry is frequently used in quantitative proteomics to detect
      differentially regulated proteins. A very important but unfortunately oftentimes
      neglected part in detecting differential proteins is the statistical analysis.
      Data from proteomics experiments are usually high-dimensional and hence require
      profound statistical methods. It is especially important to already correctly
      design a proteomic experiment before it is conducted in the laboratory. Only this
      can ensure that the statistical analysis is capable of detecting truly
      differential proteins afterwards. This chapter thus covers aspects of both
      statistical planning and the actual analysis of quantitative proteomic
      experiments.

PMID- 22665291
TI  - The whereabouts of 2D gels in quantitative proteomics.
AB  - Two-dimensional gel electrophoresis has been instrumental in the development of
      proteomics. Although it is no longer the exclusive scheme used for proteomics,
      its unique features make it a still highly valuable tool, especially when
      multiple quantitative comparisons of samples must be made, and even for large
      samples series. However, quantitative proteomics using 2D gels is critically
      dependent on the performances of the protein detection methods used after the
      electrophoretic separations. This chapter therefore examines critically the
      various detection methods (radioactivity, dyes, fluorescence, and silver) as well
      as the data analysis issues that must be taken into account when quantitative
      comparative analysis of 2D gels is performed.

PMID- 22665292
TI  - Proteome analysis with classical 2D-PAGE.
AB  - Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) is based on the
      combination of two orthogonal separation techniques. In the first dimension,
      proteins are separated by their isoelectric point, a technique known as
      isoelectric focusing (IEF). There are two important variants of IEF, which are
      carrier-ampholine (CA)-based IEF and immobilized pH gradient (IPG)-based IEF. In
      the second dimension, proteins are further separated by their electrophoretic
      mobility using SDS-PAGE. Finally, proteins can be visualized and quantified by
      different staining procedures, such as Coomassie, silver, or fluorescence
      staining. This chapter gives detailed protocols for 2D-PAGE, using both CA- and
      IPG-based separation in the first dimension.

PMID- 22665293
TI  - Fast and sensitive coomassie staining in quantitative proteomics.
AB  - Proteins separated by two-dimensional gel electrophoresis can be visualized by in
      gel detection using -different staining methods. Ideally, the dye should bind non
      covalently to the protein following a linear response curve. Since protein
      concentrations in biological systems may vary by six or more orders of magnitude
      (Corthals GL et al., Electrophoresis 21(6):1104-1115, 2000), the staining should
      allow for a detection of very low protein amounts. At the same time, saturation
      effects have to be avoided because they impede normalized quantification.Most
      proteomics laboratories apply Coomassie, silver, or fluorescent stains. Using the
      colloidal properties of Coomassie dyes, detection limits at the lower nanogram
      level can meanwhile be achieved. Characteristics like ease of use, low cost, and
      compatibility with downstream characterization methods such as mass spectrometry,
      therefore, make colloidal Coomassie staining well suited for the in-gel detection
      method in quantitative proteomics.

PMID- 22665294
TI  - Silver staining of 2D electrophoresis gels.
AB  - Silver staining is used to detect proteins after electrophoretic separation on
      polyacrylamide gels. It -combines excellent sensitivity (in the low nanogram
      range) with the use of very simple and cheap equipment and chemicals. For its use
      in proteomics, two important additional features must be considered,
      compatibility with mass spectrometry and quantitative response. Both features are
      discussed in this chapter, and optimized silver staining protocols are proposed.

PMID- 22665295
TI  - Differential proteome analysis using 2D-DIGE.
AB  - Classical two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) allows
      comparison and -quantitation of proteomes by visualization of protein patterns
      using gel stains and comparative image analysis. The introduction of fluorescent
      reagents for protein labeling (difference in-gel electrophoresis or DIGE) has
      brought substantial improvement in this field. It provides multiplexing of up to
      three samples in one gel, higher sensitivity compared to normal protein staining
      methods, and a higher linear range for quantitation. This article gives detailed
      protocols for 2D-DIGE, including both minimal as well as saturation labeling.

PMID- 22665296
TI  - Quantitative mass spectrometry-based proteomics: an overview.
AB  - In recent years, mass spectrometry has moved more than ever before into the front
      line of protein-centered research. After being established at the qualitative
      level, the more challenging question of quantification of proteins and peptides
      using mass spectrometry has become a focus for further development. In this
      chapter, we discuss and review the strategies and problems of the methods
      currently in use for the quantitative analysis of peptides, proteins, and finally
      proteomes by mass spectrometry. The common themes, the differences, and the
      potential pitfalls of the main approaches are presented in order to provide a
      survey of the emerging field of quantitative, mass spectrometry-based proteomics.

PMID- 22665297
TI  - Robust workflow for iTRAQ-based peptide and protein quantification.
AB  - Quantitative proteomics has become a routinely used technique to globally compare
      protein content and expression profiles of biological samples, for instance after
      differential stimulation. In this context, chemical stable isotope-based labeling
      techniques, such as ICAT and iTRAQ, have been successfully applied in a large
      variety of studies. Since iTRAQ labels are isobaric, quantitation is conducted on
      the MS/MS level. Consequently, up to eight samples can be multiplexed and
      quantified in a single experiment without increasing sample complexity. Here, we
      present a robust workflow to conduct iTRAQ quantification of biological samples
      such as human platelets, which comprises (a) an adequate sample preparation
      procedure, (b) an optimized tryptic digestion protocol, (c) SPE desalting and
      subsequent peptide labeling using a 4-plex iTRAQ labeling kit, and (d)
      fractionation of the obtained peptide mixture by strong cation exchange
      chromatography.

PMID- 22665298
TI  - Relative protein quantification by MS/MS using the tandem mass tag technology.
AB  - The determination of protein changes related to stimuli such as pathological
      conditions is the core task of many proteomic studies. In the past decade,
      concomitantly to the increasing role of mass spectrometry (MS), several
      strategies have been implemented for the relative quantification of proteins with
      MS. Stable isotopic labels are introduced via metabolic, enzymatic, or chemical
      routes in different samples for their distinction during MS detection. Relative
      quantification is achieved by comparison of MS or tandem MS (MS/MS) signals of
      the differentially labeled moieties. Isobaric tagging is an elegant chemical
      isotope incorporation based on tags with an identical chemical structure and same
      total mass but with labile parts under collision-activated dissociation, the so
      called reporter ions. The reporter ions are characteristic of each tag form and
      detected at distinct m/z. The TMT, iTRAQ, and ExacTag are examples of such
      technology. Experimental design, sample preparation and separation, MS
      acquisition parameters, and data analysis are the key steps to achieve accurate
      and precise quantitative measurements. We describe herein an isoelectric focusing
      shotgun proteomics workflow for the relative quantification of proteins in
      complex mixtures by MS/MS using tandem mass tags.

PMID- 22665299
TI  - A rapid approach for isobaric peptide termini labeling.
AB  - Isobaric peptide termini labeling (IPTL) is a recently introduced approach to the
      chemical labeling of peptides with isotopic reagents. Peptides derived from two
      different samples are labeled at the N terminus and at the C terminus with
      isotopically labeled reagents that have identical mass differences. To obtain
      isobaric peptides, labeling is carried out such that the introduced mass increase
      at one terminus will exactly match the mass decrease at the other terminus (and
      the other way around). This results in product ion spectra that display the
      quantitative difference of the peptide signal derived from the two samples for
      every b-ion and y-ion in the spectrum. The original IPTL approach required the
      selective modification of lysines followed by C-18 micropurification of modified
      peptides and reaction of the N termini. Here, we describe a new approach for IPTL
      that is based on the selective modification of the peptide N termini with
      succinic anhydride and subsequent reductive amination of C-terminal lysines with
      formaldehyde and cyanoborohydride. Both reactions can be carried out in one pot
      within 10 min and without C-18 micropurification. In addition, we present the
      software package IsobariQ for straightforward data analysis.

PMID- 22665300
TI  - Isotope-coded protein label.
AB  - A great variety of technologies using stable isotope labeling in combination with
      mass spectrometry have been described being tools to identify and relatively
      quantify proteins within complex mixtures. Here, we present a method, termed
      isotope-coded protein label (ICPL), which is capable of high-throughput
      quantitative proteome profiling on a global scale. Since ICPL is based on tagging
      stable isotope derivatives at the free amino groups of intact proteins, the
      method is applicable to any protein sample, including extracts from tissues or
      body fluids. All separation methods currently employed in proteome studies can be
      used to reduce complexity on the protein level. After enzymatic cleavage of the
      protein fractions, the ratios of peptides from different proteome states can be
      calculated by simple MS-based mass spectrometric analyses. Only peptides
      representing different expression levels in the different proteomic states are
      further analyzed by tandem-mass spectrometry to identify respective proteins. For
      quantification of proteins from multiplexed ICPL experiments, ICPLQuant was
      developed, a software package especially designed to cover the whole ICPL
      workflow. The ICPL method results in accurate and reproducible quantification of
      proteins and high sequence coverage, indispensable for a comprehensive detection
      of posttranslational modifications and discrimination of protein isoforms.

PMID- 22665301
TI  - Hydroponic isotope labeling of entire plants and high-performance mass
      spectrometry for quantitative plant proteomics.
AB  - Hydroponic isotope labeling of entire plants (HILEP) combines hydroponic plant
      cultivation and metabolic labeling with stable isotopes using (15)N-containing
      inorganic salts to label whole and mature plants. Employing (15)N salts as the
      sole nitrogen source for HILEP leads to the production of healthy-looking plants
      which contain (15)N proteins labeled to nearly 100%. Therefore, HILEP is suitable
      for quantitative plant proteomic analysis, where plants are grown in either (14)N
      or (15)N-hydroponic media and pooled when the biological samples are collected
      for relative proteome quantitation. The pooled (14)N-/(15)N-protein extracts can
      be fractionated in any suitable way and digested with a protease for shotgun
      proteomics, using typically reverse phase liquid chromatography nanoelectrospray
      ionization tandem mass spectrometry (RPLC-nESI-MS/MS). Best results were obtained
      with a hybrid ion trap/FT-MS mass spectrometer, combining high mass accuracy and
      sensitivity for the MS data acquisition with speed and high-throughput MS/MS data
      acquisition, increasing the number of proteins identified and quantified and
      improving protein quantitation. Peak processing and picking from raw MS data
      files, protein identification, and quantitation were performed in a highly
      automated way using integrated MS data analysis software with minimum manual
      intervention, thus easing the analytical workflow. In this methodology paper, we
      describe how to grow Arabidopsis plants hydroponically for isotope labeling using
      (15)N salts and how to quantitate the resulting proteomes using a convenient
      workflow that does not require extensive bioinformatics skills.

PMID- 22665302
TI  - In vivo quantitative proteome profiling: planning and evaluation of SILAC
      experiments.
AB  - Mass spectrometry-based quantitative proteomics can identify and quantify
      thousands of proteins in complex biological samples. Improved instrumentation,
      quantification strategies and data analysis tools now enable protein analysis on
      a genome-wide scale. Particularly, quantification based on stable isotope
      labeling with amino acids (SILAC) has emerged as a robust, reliable and simple
      method for accurate large-scale protein quantification. The spectrum of
      applications ranges from bacteria and eukaryotic cell culture systems to
      multicellular organisms. Here, we provide a step-by-step protocol on how to plan
      and perform large-scale quantitative proteome analysis using SILAC, from sample
      preparation to final data analysis.

PMID- 22665303
TI  - SILAC for the study of mammalian cell lines and yeast protein complexes.
AB  - Through crucial advancements in quantitative mass spectrometry (MS), proteomics
      has evolved from taking mere "snapshots" of proteomes to thoroughly studying
      dynamic changes in entire proteomes and characterizing intricate protein-protein
      interaction or signaling networks. Thus, quantitative MS-based proteomics offers
      the unique potential to place proteins into their functional context and,
      moreover, to improve our understanding of the molecular processes involved in the
      development, survival, or pathology of cells and organisms. Among the vast
      variety of techniques developed for the accurate quantification of proteins via
      MS, stable isotope labeling by amino acids in cell culture (SILAC) arguably
      represents the most elegant method. In this chapter, we provide a detailed
      protocol for the establishment of SILAC for mammalian cell culture systems. In
      addition, to exemplify the high versatility of SILAC for addressing different
      biological questions, we describe the successful "pairing" of SILAC with
      conventional affinity purification (AP)-MS approaches allowing for accurately
      characterizing protein complexes.

PMID- 22665304
TI  - Post-digestion 18O exchange/labeling for quantitative shotgun proteomics of
      membrane proteins.
AB  - The role of membrane proteins is critical for regulation of physiologic and
      pathologic cellular processes. Hence it is not surpassing that membrane proteins
      make ~70% of contemporary drug targets. Quantitative profiling of membrane
      proteins using mass spectrometry (MS)-based proteomics is critical in a quest for
      disease biomarkers and novel cancer drugs. Post-digestion (18)O exchange is a
      simple and efficient method for differential (18)O/(16)O stable isotope labeling
      of two biologically distinct specimens, allowing relative quantitation of
      proteins in complex mixtures when coupled with shotgun MS-based proteomics. Due
      to minimal sample consumption and unrestricted peptide tagging, (18)O/(16)O
      stable isotope labeling is particularly suitable for amount-limited protein
      specimens typically encountered in membrane and clinical proteomics. This chapter
      describes a protocol that relies on shotgun proteomics for quantitative profiling
      of the detergent-insoluble membrane proteins isolated from HeLa cells,
      differentially transfected with plasmids expressing HIV Gag protein and its
      myristylation-defective N-terminal mutant. Whilst this protocol depicts
      solubilization of detergent-insoluble membrane proteins coupled with post
      digestion (18)O labeling, it is amenable to any complex membrane protein mixture.
      Described approach relies on solubilization and tryptic digestion of membrane
      proteins in a buffer containing 60% (v/v) methanol followed by differential
      (18)O/(16)O labeling of protein digests in 20% (v/v) methanol buffer. After
      mixing, the differentially labeled peptides are fractionated using off-line
      strong cation exchange (SCX) followed by on-line reversed phase nanoflow reversed
      phase liquid chromatography (nanoRPLC)-MS identification/quantiation of
      peptides/proteins. The use of methanol-based buffers in the context of the post
      digestion (18)O exchange/labeling eliminates the need for detergents or
      chaotropes that interfere with LC separations and peptide ionization. Sample
      losses are minimized because solubilization, digestion, and stable isotope
      labeling are carried out in a single tube, avoiding any sample transfer or buffer
      exchange between these steps.

PMID- 22665305
TI  - Application of label-free proteomics for differential analysis of lung carcinoma
      cell line A549.
AB  - A label-free solution basing on a highly reproducible and stable LC-MS/MS system
      allows quantitative proteome analyses. Due to nonlabeling approach, the label
      free method has the potential to measure samples from clinical specimen
      monitoring and comparing thousands of proteins. The presented label-free workflow
      includes in-solution digest, LC-MS analyses, data evaluation by the means of
      ProgenesisTM software, and validation of the differential proteins. We
      successfully applied this workflow in a proteomics study analyzing the human lung
      carcinoma cell line A549 treated with transforming growth factor beta 1, a cell
      culture model of lung fibrosis. The differential analysis of only 1 MUg protein
      per sample led to 202 significantly regulated proteins.

PMID- 22665306
TI  - Absolute quantification of proteins using standard peptides and multiple reaction
      monitoring.
AB  - Mass spectrometry (MS) is a powerful tool for protein identification and has
      therefore become indispensable for proteome studies. In recent years, simple
      protein identification by MS has become routine, and more attention has been
      devoted to the MS-based investigation of posttranslational modifications and the
      quantification of proteins and peptides. Numerous methods and techniques for
      relative quantification of proteins by MS have emerged and have been applied
      successfully to answer various questions of protein abundance. Absolute
      quantification is often applied in clinical research and biomarker discovery, but
      has also been used to determine protein stoichiometries in protein complexes.
      However, the number of methods available for absolute quantification is still
      restricted and often requires the generation of standard peptides containing
      amino acids labeled with stable isotopes, although label-free approaches are also
      gaining importance. Complete hydrolysis of the proteins to be quantified is known
      to be one of the prerequisites for reliable absolute quantification, and
      selection and suitability of the standard peptides are critical factors in the
      planning of a quantitative study. Along the different methods to read out
      quantitative signals by MS, multiple reaction monitoring (MRM) has proven to be
      most suitable, with a wide linear range. However, analysis by MRM is a targeted
      approach and each case requires the individual design of suitable assays, which
      is a time-consuming step during the preliminary analysis. In this chapter, we
      present various protocols for in-solution hydrolysis, manual selection of
      suitable standard peptides, and design of MRM transitions.

PMID- 22665307
TI  - Absolute multiplexed protein quantification using QconCAT technology.
AB  - In addition to protein identification, protein quantification is becoming a key
      output of proteomic experiments. Although relative quantification techniques are
      more commonplace and central to discovery proteomics, most assays require
      absolute quantification. The growth in systems biology has also increased the
      demand for absolute protein abundance values for input into models. QconCATs are
      created by concatenating peptide sequences taken from the target proteins into
      artificial proteins. The QconCAT acts as a source of internal standards and
      enables parallel absolute quantification of multiple proteins. QconCATs are
      typically applied in targeted proteomic workflows and so benefit from the greater
      sensitivity and wider dynamic range of these approaches. In this chapter, we
      discuss the design, construction, expression, and deployment of a QconCAT and the
      resulting experiments required for multiplex absolute quantification.

PMID- 22665308
TI  - A practical guide to the FLEXIQuant method.
AB  - A protein molecule exists as a heterogeneous population of posttranslationally
      modified forms, which are of potential interest to biologists. However, due to
      detection or methodology limitations, they remain uncharacterized. When a protein
      does become a prioritized interest in a laboratory, workflows aimed for its
      purification and characterization are implemented. Inherent in these workflows is
      the enrichment of the protein from the biological lysate, rendering it an ideal
      sample for mass spectrometry (MS), as detection of several peptides is greatly
      increased. In order to capitalize on this enhanced detection of the protein of
      interest, we have developed a full-length expressed protein quantification
      standard (FLEXIQuant standard) that is in vitro synthesized, devoid of
      posttranslational modifications (PTMs), and implemented into the purification
      workflow of the endogenous counterpart-as such it serves as an internal MS
      standard. FLEXIQuantification allows for the unbiased identification of peptides
      undergoing PTM as a function of a particular biological state. The extent of PTM
      is also quantified, providing further insight into the regulation of the protein.

PMID- 22665309
TI  - Label-free protein quantitation using weighted spectral counting.
AB  - Mass spectrometry (MS)-based shotgun proteomics allows protein identifications
      even in complex biological samples. Protein abundances can then be estimated from
      the counts of MS/MS spectra attributable to each protein, provided that one
      corrects for differential MS-detectability of the contributing peptides. We
      describe the use of a method, APEX, which calculates Absolute Protein EXpression
      levels based on learned correction factors, MS/MS spectral counts, and each
      protein's probability of correct identification.The APEX-based calculations
      consist of three parts: (1) Using training data, peptide sequences and their
      sequence properties, a model is built that can be used to estimate MS
      detectability (O (i)) for any given protein. (2) Absolute abundances of proteins
      measured in an MS/MS experiment are calculated with information from spectral
      counts, identification probabilities and the learned O (i)-values. (3) Simple
      statistics allow for significance analysis of differential expression in two
      distinct biological samples, i.e., measuring relative protein abundances. APEX
      based protein abundances span more than four orders of magnitude and are
      applicable to mixtures of hundreds to thousands of proteins from any type of
      organism.

PMID- 22665310
TI  - Discovering the phosphoproteome of the hydrophobic cytochrome c oxidase membrane
      protein complex.
AB  - Many cellular processes are regulated by reversible phosphorylation to change the
      activity state of proteins. One example is cytochrome c oxidase (COX) with its
      important function for energy metabolism in the mitochondria. The phosphorylation
      of this enzyme is a prerequisite for the allosteric ATP-inhibition and therefore
      necessary to adapt energy production to ATP demand of the cell. Its hydrophobic
      nature hampers the recognition of phosphorylated amino acids in most subunits of
      this complex, and as a consequence, only a few phosphorylation sites were
      identified by mass spectrometry. We describe here a method that enables the
      analysis of integral membrane proteins by chemical cleavage with cyanogen bromide
      (BrCN), a method that improves the mass spectrometric detection of hydrophobic
      proteins. The low abundance of phosphopeptides requires efficient enrichment
      techniques, such as TiO(2)-based methods. However, this strategy failed in our
      hands when just BrCN-cleaved peptides were used. Only an additional size
      reduction with trypsin produced peptides with optimal properties for enrichment
      and MS-identification. Another bottleneck was the correct assignment of
      phosphoserine and phosphothreonine because peptide-ion fragmentation by collision
      induced dissociation (CID) often results in neutral loss of HPO(3) or H(2)PO(4)
      from the precursor, decreasing fragmentations that define the peptide sequence
      and the phosphorylation site. The additional usage of electron transfer
      dissociation (ETD) as an alternative fragmentation method enabled the precise
      assignment of the phosphorylated amino acids. In a total of six, new
      phosphorylation sites of four COX-subunits were identified by this strategy.

PMID- 22665311
TI  - KiC assay: a quantitative mass spectrometry-based approach for kinase client
      screening and activity analysis [corrected].
AB  - Protein phosphorylation is one of the most important posttranslational
      modifications (PTMs) involved in the transduction of cellular signals. The number
      of kinases in eukaryotic genomes ranges from several hundred to over one
      thousand. And with rapidly evolving mass spectrometry (MS)-based approaches,
      thousands to tens of thousands of phosphorylation sites (phosphosites) have been
      reported from various eukaryotic organisms, from man to plants. In this relative
      context, few bona fide kinase-client relationships have been identified to date.
      To merge the gap between these phosphosites and the cognate kinases that beget
      these events, comparable large-scale methodologies are required. We describe in
      detail a MS-based method for identifying kinase-client interactions and
      quantifying kinase activity. We term this novel Kinase-Client assay, the KiC
      assay. The KiC assay relies upon the fact that substrate specificities of many
      kinases are largely determined by primary amino acid sequence or phosphorylation
      motifs, which consist of key amino acids surrounding the phosphorylation sites.
      The workflow for detecting kinase-substrate interactions includes four major
      steps: (1) preparation of purified kinases and synthetic peptide library, (2) in
      vitro kinase peptide library assay, (3) liquid chromatography (LC)-tandem MS
      (MS/MS) analysis, and (4) data processing and interpretation. Kinase activity is
      quantified with the KiC assay by monitoring spectral counts of phosphorylated and
      unphosphorylated peptides as the readout from LC-tandem mass spectrometry. The
      KiC assay can be applied as a discovery assay to screen kinases against a
      synthetic peptide library to find kinase-client relationships or as a targeted
      assay to characterize kinase kinetics.

PMID- 22665312
TI  - Robust and high-throughput sample preparation for (semi-)quantitative analysis of
      N-glycosylation profiles from plasma samples.
AB  - High-throughput quantitative or semiquantitative glycoanalytical procedures are
      urgently required for biomarker discovery and quality control of glycoprotein
      pharmaceuticals. We describe here a strategy for high-throughput sample
      preparation for the relative quantitation of N-glycan patterns of human plasma
      glycoproteins. To this end, efficient glycan release is combined with a robust
      labeling step. Sample purification is achieved using solid phase extraction with
      a hydrophilic interaction chromatography stationary phase, which allows the
      separation of the labeled glycans from excess label, proteins, and matrix
      constituents such as salts and lipids. We show that the obtained labeled glycan
      sample solution is directly compatible with a number of downstream analytical
      techniques such as hydrophilic interaction and reverse-phase chromatography,
      capillary electrophoresis, and matrix-assisted laser desorption ionization mass
      spectrometry. High throughput is achieved by conducting all sample preparation
      steps in the 96-well format. The robustness and repeatability of the sample
      preparation strategy is evaluated.

PMID- 22665313
TI  - Quantitative redox proteomics: the NOxICAT method.
AB  - Because of its versatile chemical properties, the amino acid cysteine plays a
      variety of vital roles in proteins. It can form structure-stabilizing elements
      (e.g., disulfide bonds), coordinate metal cofactors and is part of the catalytic
      center of many enzymes. Recently, a new role has been discovered for cysteine: so
      called redox-sensitive proteins use the thiol group of cysteine as a specific
      sensor for Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). The
      oxidation of such a redox-active cysteine, e.g., under conditions of elevated
      cellular ROS or RNS levels (oxidative or nitrosative stress), often results in a
      reversible thiol modification. This, in turn, might lead to structural changes
      and altered protein activity. When the oxidative stress subsides, cellular
      antioxidant systems, including thioredoxin and glutathione can reduce the redox
      active cysteine and restore the original structure and activity of the redox
      sensitive protein. This makes oxidative thiol modifications an attractive
      mechanism for cellular redox sensing and signaling.To study the target cysteines
      of oxidative and nitrosative stress and to quantify the extent of the thiol
      modifications generated under these conditions, we have recently developed a
      thiol trapping technique using isotope coded affinity tag (ICAT) chemistry (1).
      With this method, reduced cysteines are selectively labeled with the isotopically
      light form of ICAT and oxidized cysteines with the isotopically heavy form of
      ICAT. Thus we could globally quantify the ratio of reduced and oxidized cysteines
      in cellular proteins based on the modified peptide masses. Here, we present an
      expansion of this method, which we term NOxICAT, because it uses ICAT chemistry
      to detect changes in thiol modifications of proteins upon Nitrosative and
      Oxidative stress. The NOxICAT-method is a highly specific and quantitative method
      to study the global changes in the thiol redox state of cellular proteins under a
      variety of physiological and pathological stress conditions.

PMID- 22665314
TI  - Quantitative analysis of S-nitrosylated proteins.
AB  - Protein S-nitrosylation is the covalent binding of nitric oxide to specific
      cysteine residues in proteins. This modification influences a large number of
      cellular events and signaling processes. As this process is finely regulated in
      vivo, the level of nitrosylation changes in response to different stimuli. Since
      its introduction, the biotin-switch technique (BST) is the most used indirect
      method for the study of S-nitrosylation both in vivo and in vitro and its
      coupling with mass spectrometry-based proteomics lead to the identification of
      the S-nitroso proteome in different organisms. However, this method does not give
      any information about the posttranslational modification level on the same
      residue in different biological conditions. Quantitative proteomic methods can
      assess the relative change in S-nitrosylation for hundreds sites in a single
      experiment. Stable isotope labeling by aminoacids in cell culture (SILAC) is one
      of the most used and accurate quantitative techniques in MS-based proteomics.
      Here we present a SILAC-based method for the quantification of endogenously S
      nitrosylated proteins in RAW 264.7 cells.

PMID- 22665316
TI  - Identification of endogenous SUMO1 accepter sites by mass spectrometry.
AB  - Posttranslational modification (PTM) by the covalent conjugation of small
      ubiquitin-like modifier (SUMO) plays an important role in many biological
      processes, such as cell cycle progression, transcriptional regulation,
      subcellular transport, and other processes. An in-depth understanding of the
      function of SUMOylation requires the discovery of SUMO accepter sites. However,
      identification of endogenous SUMO-conjugated sites in higher eukaryotes by MS
      based proteomic strategies is hampered by the low abundance of SUMO conjugates,
      the large tryptic fragments of SUMO1 or SUMO2/3 and the inability to match MS/MS
      spectra by protein database search engine. In this chapter, we describe a
      powerful method to overcome at least some of these challenges. To identify SUMO
      acceptor sites in endogenous SUMO1 conjugated protein, the SUMO1 conjugates are
      purified by immunoprecipitation with anti-SUMO1 antibodies followed by SDS-PAGE
      separation and in-gel tryptic digestion. The resulting peptides are either
      performed using standard data dependent acquisition (DDA) for protein
      identification or high mass DDA to enhance the sensitivity of detection on the
      LTQ-Orbitrap mass spectrometer. Finally, a Web-based database tool, ChopNSpice,
      coupled with a protein database search engine is introduced to ease the
      identification of SUMO1 attachment sites. Although this method was initially used
      to identify SUMO1 accepter sites, it can be readily adapted to study SUMO2/3
      conjugates or even other Ubiquitin-like modifiers.

PMID- 22665315
TI  - Analysis of ubiquitinated proteome by quantitative mass spectrometry.
AB  - Protein modification by ubiquitin (Ub) is one of the most common
      posttranslational events in eukaryotic cells. Ubiquitinated proteins are destined
      to various fates such as proteasomal degradation, protein trafficking, DNA
      repair, and immune response. In the last decade, vast improvements of mass
      spectrometry make it feasible to analyze the minute amount of ubiquitinated
      components in vivo. When combined with quantitative strategies, such as stable
      isotope labeling with amino acids in cell culture (SILAC), it is capable of
      profiling ubiquitinated proteome under different experimental conditions. Here,
      we describe a procedure to perform such a study, including differential protein
      labeling by the SILAC method, enrichment of ubiquitinated species, mass
      spectrometric analysis, and quality control to reduce false positives. The
      potential challenges and limitations of the procedure are also discussed.

PMID- 22665317
TI  - Search and decoy: the automatic identification of mass spectra.
AB  - In recent years, the generation and interpretation of MS/MS spectra for the
      identification of peptides and proteins has matured to a frequently used
      automatic workflow in Proteomics. Several software solutions for the automated
      analysis of MS/MS spectra allow for high-throughput/high-performance analyses of
      complex samples. Related to MS/MS searches, target-decoy approaches have gained
      more and more popularity: in a "decoy" part of the search database nonexistent
      sequences mimic real sequences (the "target" sequences). With their help, the
      number of falsely identified peptides/proteins can be estimated after a search
      and the resulting protein list can be cut at a specified false discovery rate
      (FDR). This is an essential prerequisite for all quantitative approaches, as they
      rely on correct identifications. Especially the label-free approach "spectral
      counting"-gaining more and more popularity due to low costs and simplicity
      depends directly on the correctness of peptide-spectrum matches (PSMs). This
      work's aim is to describe five popular search engines-especially their general
      properties regarding protein identification, but also their quantification
      abilities, if those go beyond spectral counting. By doing so, Proteomics
      researchers are enabled to compare their features and to choose an appropriate
      solution for their specific question. Furthermore, the search engines are applied
      to a spectrum data set generated from a complex sample with a Thermo LTQ Velos
      OrbiTrap (Thermo Fisher Scientific, Waltham, MA, USA). The results of the search
      engines are compared, e.g., regarding time requirements, peptides and proteins
      found, and the search engines' behavior using the decoy approach.

PMID- 22665318
TI  - Software tools for MS-based quantitative proteomics: a brief overview.
AB  - Proteomics is turning more and more towards quantitative measurements of
      biological systems. This in turn has spurred the development of numerous
      experimental methods that enable such measurements. Vast quantities of mostly
      mass spectrometric data are often generated as a result which requires the use of
      software tools that turns raw data into useful quantitative information from
      which knowledge about the biological system can eventually be derived. This
      chapter gives a brief overview of available software tools for mass spectrometry
      based quantitative proteomics.

PMID- 22665319
TI  - iTRAQ data interpretation.
AB  - Quantitative proteomic analysis can help elucidating unexplored biological
      questions; it, however, relies on highly reproducible experiments and reliable
      data processing. Among the existing strategies, iTRAQ is known as an easy to use
      method allowing relative comparison of up to eight multiplexed samples.Once the
      data is acquired it is important that the final protein quantification reflects
      the actual amounts in the samples. Data interpretation must thus be achieved with
      a constant focus on quality. Here, we describe a workflow for processing iTRAQ
      data in user-friendly environments with emphasis on quality control.

PMID- 22665320
TI  - MSQuant: a platform for stable isotope-based quantitative proteomics.
AB  - Quantitative approaches in proteomics are emerging as a powerful tool to probe
      the dynamics of protein expression across biological conditions. Thereby,
      quantification helps to recognize proteins with potential biological relevance,
      which greatly aids in the design of follow-up experiments. Although multiple
      methods have been established that are based on stable-isotope labeling and label
      free approaches, one of the remaining bottlenecks is the analysis and
      quantification of proteins in large datasets. MSQuant is a platform for protein
      quantification, capable of handling multiple labeling strategies and supporting
      several vendor data formats. Here, we report on the use and versatility of
      MSQuant.

PMID- 22665321
TI  - Lipids: Cardioprotective effects of HDL cholesterol called into question.

PMID- 22665322
TI  - Risk factors: Air pollution and cardiovascular risk during the Beijing Olympics.

PMID- 22665324
TI  - Coronary artery disease: Consider Kawasaki disease when assessing myocardial
      ischemia.

PMID- 22665326
TI  - Imaging: Same quality, less radiation exposure.

PMID- 22665328
TI  - Vascular disease: Even low-risk individuals can benefit from statin therapy.

PMID- 22665327
TI  - Cardiopulmonary resuscitation and management of cardiac arrest.
AB  - The best chance of survival with a good neurological outcome after cardiac arrest
      is afforded by early recognition and high-quality cardiopulmonary resuscitation
      (CPR), early defibrillation of ventricular fibrillation (VF), and subsequent care
      in a specialist center. Compression-only CPR should be used by responders who are
      unable or unwilling to perform mouth-to-mouth ventilations. After the first
      defibrillator shock, further rhythm checks and defibrillation attempts should be
      performed after 2 min of CPR. The underlying cause of cardiac arrest can be
      identified and treated during CPR. Drugs have a limited effect on long-term
      outcomes after cardiac arrest, although epinephrine improves the success of
      resuscitation, and amiodarone increases the success of defibrillation for
      refractory VF. Supraglottic airway devices are an alternative to tracheal
      intubation, which should be attempted only by skilled rescuers. Care after
      cardiac arrest includes controlled reoxygenation, therapeutic hypothermia for
      comatose survivors, percutaneous coronary intervention, circulatory support, and
      control of blood-glucose levels and seizures. Prognostication in comatose
      survivors of cardiac arrest needs a careful, multimodal approach using clinical
      and electrophysiological assessments after at least 72 h.

PMID- 22665331
TI  - Comparison between measured and calculated length of side branch ostium in
      coronary bifurcation lesions with intravascular ultrasound.
AB  - PURPOSE: Accurate evaluation of side branch (SB) ostium could be critical to the
      treatment of bifurcation lesions. We compared measured and calculated values of
      side branch ostial length (SBOL) in coronary bifurcation lesions with
      intravascular ultrasound (IVUS). MATERIALS AND METHODS: Pre-intervention and post
      intervention IVUS was performed in 113 patients who underwent stent implantation
      of bifurcation lesions. For the IVUS longitudinal reconstruction of the
      bifurcation lesions, SBOL, SB diameter, and the angle between the distal portion
      of the main vessel (MV) and SB were directly measured. In addition, SBOL was
      calculated as: SB diameter/ sin (angle between distal MV and SB). The
      relationship between measured and calculated SBOL was then evaluated. RESULTS:
      The angled between the distal MV and SB were 57.3+/-12.4 degrees  at pre
      intervention and 59.4+/-12.6 degrees  at post-intervention. The mean measured and
      calculated SBOL values were 2.91+/-0.86 mm and 3.06+/-0.77 mm at pre-intervention
      and 2.79+/-0.82 mm and 2.92+/-0.69 mm at post-intervention, respectively.
      Differences between measured and calculated SBOL were 0.15+/-0.44 mm at pre
      intervention and 0.13+/-0.41 mm at post-intervention. We found that calculated
      SBOL was correlated with measured SBOL (pre-intervention r=0.863, p<0.001; post
      intervention r=0.868, p<0.001). CONCLUSION: There was a good correlation between
      measured and calculated SBOLs of the bifurcation lesions in IVUS longitudinal
      reconstruction. SBOL in the bifurcation lesions can therefore be estimated using
      the SB diameter and the angle between distal MV and SB.

PMID- 22665330
TI  - Leptin as a modulator of neuroendocrine function in humans.
AB  - Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of
      energy stored in fat, plays a central role in regulating human energy
      homeostasis. In addition, leptin plays a significant permissive role in the
      physiological regulation of several neuroendocrine axes, including the
      hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes.
      Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a
      state of energy deprivation. Hypoleptinemia can be a congenital or acquired
      condition, and is associated with alterations of the aforementioned axes aimed at
      promoting survival. More specifically, gonadotropin levels decrease and become
      less pulsatile under conditions of energy deprivation, and these changes can be
      at least partially reversed through leptin administration in physiological
      replacement doses. Similarly, leptin deficiency is associated with thyroid axis
      abnormalities including abnormal levels of thyrotropin-releasing hormone, and
      leptin administration may at least partially attenuate this effect. Leptin
      deficiency results in decreased insulin-like growth factor 1 levels which can be
      partially ameliorated through leptin administration, and leptin appears to have a
      much more pronounced effect on the growth of rodents than that of humans.
      Similarly, adrenal axis function is regulated more tightly by low leptin in
      rodents than in humans. In addition to congenital leptin deficiency, conditions
      that may be associated with decreased leptin levels include hypothalamic
      amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes.
      Accumulating evidence from proof of concept studies suggests that leptin
      administration, in replacement doses, may ameliorate neuroendocrine abnormalities
      in individuals who suffer from these conditions.

PMID- 22665332
TI  - The relationship between coronary artery calcification and renal function in
      nondialyzed patients.
AB  - PURPOSE: Coronary artery calcification (CAC) has been described in individuals
      with chronic kidney disease (CKD), and its presence is associated with an
      increased risk of cardiovascular death. However, it is unclear whether there is
      an independent relationship between renal function and CAC. Therefore, we
      evaluated the association between renal function and CAC. MATERIALS AND METHODS:
      We retrospectively reviewed 870 Korean patients who had undergone computed
      tomographic coronary angiography. The glomerular filtration rate (GFR) was
      estimated using the Modification of Diet in Renal Disease study formula with an
      ethnic factor for the Korean population. The CKD stages were classified using
      estimated GFR (eGFR) and proteinuria. RESULTS: The mean age of the participants
      was 56.8+/-11.8 years, and the mean eGFR was 89.4+/-16.5 mL/min/1.73 m2.
      Hypertension and diabetes were noted in 41.5 and 17.0% of patients, respectively.
      There were 584 and 286 patients with no CAC and with CAC, respectively. After
      adjusting for confounding variables, late stage CKD was associated with CAC [odds
      ratio (OR) 2.80, 95% confidence interval (CI) 1.05-7.46]. However, early stage
      CKD was not associated with CAC (OR 1.61, 95% CI 0.92-2.82). Diabetes was an
      independent risk factor of CAC (OR 2.06, 95% CI 1.36-3.13). There was no
      significant association between proteinuria and CAC (OR 1.65, 95% CI 0.96-2.85).
      CONCLUSION: CAC is related to late stage CKD in nondialyzed patients. These
      findings emphasize that individuals with CAC should be considered a high-risk
      population for decreased renal function.

PMID- 22665333
TI  - Antidiabetic effects of Corni Fructus extract in streptozotocin-induced diabetic
      rats.
AB  - PURPOSE: Diabetes is the leading cause of end-stage renal failure. The present
      study was undertaken to characterize the effects of Corni Fructus on diabetic
      nephropathy in streptozotocin-induced diabetic rats and their mechanisms.
      MATERIALS AND METHODS: Streptozotocin-diabetic rats were orally administrated
      with Corni Fructus at a dose of 100, 200 or 400 mg/kg body mass for 40 days.
      RESULTS: Corni Fructus-treated diabetic rats showed significant decreases of
      blood glucose, urinary protein levels and water consumption. Corni Fructus also
      reduced serum total cholesterol, total triglyceride and low-density lipoprotein
      cholesterol levels, and showed a tendency of enhancing high-density lipoprotein
      cholesterol level. Levels of serum albumin and creatinine in diabetic rats were
      also significantly reduced by Corni Fructus administration at a dose of 200 and
      400 mg/kg body mass compared with non-treated diabetic rats. Corni Fructus
      increased catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidose
      (GSH-px) activities in the kidneys of diabetic rats. Furthermore, Corni Fructus
      treatment enhanced renal peroxisome proliferator-activated receptor-gamma
      (PPARgamma) expression in diabetic rats. CONCLUSION: These results demonstrated
      that Corni Fructus may have the potential to protect the animals from diabetic
      nephropathy by amelioration of oxidative stress and stimulation of PPARgamma
      expression.

PMID- 22665334
TI  - The influence of diabetes mellitus on short-term outcomes of patients with
      bleeding peptic ulcers.
AB  - PURPOSE: Little information is available on the influence of diabetes mellitus on
      the short-term clinical outcomes of patients with bleeding peptic ulcers. The aim
      of this study is to investigate whether diabetes mellitus influences the short
      term clinical outcomes of patients with bleeding peptic ulcers using a Japanese
      national administrative database. MATERIALS AND METHODS: A total of 4863 patients
      treated by endoscopic hemostasis on admission for bleeding peptic ulcers were
      referred to 586 participating hospitals in Japan. We collected their data to
      compare the risk-adjusted length of stay (LOS) and in-hospital mortality of
      patients with and without diabetes mellitus within 30 days. Patients were divided
      into two groups: patients with diabetes mellitus (n=434) and patients without
      diabetes mellitus (n=4429). RESULTS: Mean LOS in patients with diabetes mellitus
      was significantly longer than those without diabetes mellitus (15.8 days vs. 12.5
      days, p<0.001). Also, higher in-hospital mortality within 30 days was observed in
      patients with diabetes mellitus compared with those without diabetes mellitus
      (2.7% vs. 1.1%, p=0.004). Multiple linear regression analysis revealed that
      diabetes mellitus was significantly associated with an increase in risk-adjusted
      LOS. The standardized coefficient was 0.036 days (p=0.01). Furthermore, the
      analysis revealed that diabetes mellitus significantly increased the risk of in
      hospital mortality within 30 days (odds ratio=2.285, 95% CI=1.161-4.497,
      p=0.017). CONCLUSION: This study demonstrated that presence of diabetes mellitus
      significantly influences the short-term clinical outcomes of patients with
      bleeding peptic ulcers.

PMID- 22665335
TI  - Removal of kidney stones by extracorporeal shock wave lithotripsy is associated
      with delayed progression of chronic kidney disease.
AB  - PURPOSE: This study aimed to elucidate whether stone removal by extracorporeal
      shock wave lithotripsy (ESWL) is associated with delayed chronic kidney disease
      (CKD) progression. MATERIALS AND METHODS: We conducted a retrospective analysis
      of 131 nephrolithiasis patients with stage 3 and 4 CKD. We collected baseline
      clinical and laboratory data, kidney stone characteristics, and history of
      receiving ESWL. We classified study patients into two groups according to whether
      they underwent ESWL or not (Non-ESWL group vs. ESWL group). We initially compared
      annual estimated glomerular filtration rate (eGFR) changes of Non-ESWL group with
      those of ESWL group before undergoing ESWL. In the next step, we sought to
      compare annual eGFR changes in the same patients before and after ESWL. Finally,
      we compared annual eGFR changes between success and failure groups among patients
      undergoing ESWL. RESULTS: The mean age of the patients was 62 years and 72.5%
      were male. The mean observation period was 3.2 years. Non-ESWL group and ESWL
      group before undergoing ESWL showed similar annual eGFR changes (-1.75+/-6.5 vs. 
      1.63+/-7.2 mL/min/1.73 m2/year, p=0.425). However, eGFR declined slower after
      undergoing ESWL than before ESWL (annual eGFR changes, -0.29+/-6.1 vs. -1.63+/
      7.2 mL/min/1.73 m2/year, p<0.05). In addition, among patients in ESWL group, eGFR
      declined faster in the failure group than in the success group (annual eGFR
      change, -1.01+/-4.7 vs. -0.05+/-5.2 mL/min/1.73 m2/year, p<0.05). CONCLUSION: Our
      results suggest that stone removal by ESWL is associated with delayed
      deterioration of renal function in CKD patients with nephrolithiasis.

PMID- 22665336
TI  - The clinical characteristics of steroid responsive nephrotic syndrome of children
      according to the serum immunoglobulin E levels and cytokines.
AB  - PURPOSE: The nephrotic syndrome (NS) is characterized by the favorable response
      to glucocorticoid therapy and the development of NS may be associated with
      dysfunctional immune systems. In order to investigate the serum immunoglobulin E
      (IgE) levels and cytokines activity in pediatric NS, the total of 32 steroid
      responsive NS patients and 5 healthy controls were enrolled in this study.
      MATERIALS AND METHODS: All patients were divided into two groups according to the
      initial serum IgE levels, such as normal and high IgE group, and their clinical
      characteristics were evaluated. In addition, serum levels of interleukin (IL)-4,
      IL-5, IL-10 and transforming growth factor (TGF)-beta were compared and
      correlated with serum albumin, proteinuria by means of disease severity, and
      cytokines. RESULTS: In the high IgE group, the higher comorbidity of allergic
      diseases and relapsing rate, the longer duration of steroid therapy before
      initial remission, and the higher serum IL-4 and IL-5 levels were found. In all
      patients, initially higher serum levels of IL-4 and IL-5 declined to normal
      levels after steroid therapy, whereas the serum IL-10 levels showed no
      significant difference between nephrotic phase (heavy proteinuria) and remission
      phase (no proteinuria) of NS. The serum TGF-beta levels of the nephrotic phase
      were significantly lower than those of remission phase or control group, and
      returned to normal control levels after steroid therapy. CONCLUSION: This study
      indicates that initial IgE level is associated with steroid responsiveness and
      disease severity, and cytokine activities may also be related to the pathogenesis
      of pediatric steroid responsive NS.

PMID- 22665337
TI  - Recurrent varicoceles: causes and treatment using angiography and magnification
      assisted subinguinal varicocelectomy.
AB  - PURPOSE: To investigate the causes of varicocele recurrence and assess the use of
      embolization and subinguinal varicocelectomy in its treatment in patients with
      angiography and subinguinal varicocelectomy. MATERIALS AND METHODS: The present
      study involved 15 patients with recurrent varicoceles. The mean patient age was
      21.2 years (range: 12-42 years). Preoperative angiography was performed in 11
      patients. Embolization was used in patients with patent internal spermatic veins
      (ISVs). Patients without patent ISVs or preoperative angiography underwent
      magnification-assisted subinguinal varicocelectomy which included testicular
      retrieval and ligation of all collateral veins except arteries and deferential
      veins. RESULTS: Seven among 11 patients (64%) which had preoperative angiography
      had patent ISVs and underwent embolization and 8 patients underwent subinguinal
      varicocelectomy. Of those 8 patients, 6 had dilated ISVs and external spermatic
      veins (ESVs), one had dilated ISVs and gubernacular veins, and one had dilated
      ISVs, ESVs and gubernacular veins. No patient experienced recurrence or testis
      atrophy. CONCLUSION: Patent ISVs or collateral veins may be the cause of
      recurrence after varicocelectomy. Angiographic embolization was successful in 64%
      of recurrent varicoceles patients with patent ISVs. However, microscope-assisted
      subinguinal varicocelectomy may be the best overall treatment for patients with
      recurrent varicoceles.

PMID- 22665338
TI  - Differential diagnosis of complex renal cysts based on lesion size along with the
      Bosniak renal cyst classification.
AB  - PURPOSE: To identify size criteria for complex cystic renal masses that can
      distinguish renal cell carcinoma from benign cysts supplementing the Bosniak
      classification. MATERIALS AND METHODS: We reviewed the records of 97 patients who
      underwent surgery for complex cystic renal masses from January 2001 to April
      2010. The pathological results were compared with the lesion sizes measured by
      preoperative computed tomography and other radiological features (contrast
      enhancement, irregularities of cyst walls and septa, and calcification) were also
      obtained for categorization according to the Bosniak renal cyst classification.
      RESULTS: Malignancy was significantly associated with cyst size (>2 cm), male
      gender, and younger patient age (<50 years). According to the Bosniak
      classification, there was no category I cyst, and all 8 category II cysts were
      benign. However, 3 of 18 (17%) category IIF cysts, 21 of 39 (54%) category III
      cysts, and 29 of 32 (90%) category IV cysts were malignant. All category IIF
      cysts were benign in patients older than 50 years of age. CONCLUSION: Many
      complex cystic renal masses smaller than 2 cm were benign. We suggest that lesion
      size should be taken into account when formulating treatment plans for complex
      cystic renal masses.

PMID- 22665339
TI  - Five-year follow-up results of a randomized controlled trial comparing bipolar
      plasmakinetic and monopolar transurethral resection of the prostate.
AB  - PURPOSE: To report the 5-year follow-up results of a randomized controlled trial
      comparing bipolar transurethral resection of the prostate (TURP) with standard
      monopolar TURP for the treatment of benign prostatic obstruction (BPO). MATERIALS
      AND METHODS: A total of 220 patients were randomized to bipolar plasmakinetic
      TURP (PK-TURP) or monopolar TURP (M-TURP). Catheterization time was the primary
      endpoint of this study. Secondary outcomes included operation time, hospital
      stay, as well as decline in postoperative serum sodium and hemoglobin levels. All
      patients were assessed preoperatively and followed-up at 1, 6, 12, 24, 36, 48,
      and 60 months postoperatively. Parameters assessed included quality of life,
      transrectal ultrasound, serum prostate-specific antigen level, postvoid residual
      urine volume, maximum urinary flow rates (Q(max)), and International Prostate
      Symptom Score. Patient baseline characteristics, perioperative data including
      complications, and postoperative outcomes were compared. Complication occurrence
      was graded according to the modified Clavien classification system. RESULTS: PK
      TURP was significantly superior to M-TURP in terms of operation time,
      intraoperative irrigation volume, resected tissue weight, decreases in hemoglobin
      and sodium, postoperative irrigation volume and time, catheterization time, and
      hospital stay. At 5 years postoperatively, efficacy was comparable between arms.
      No differences were detected in safety outcomes except that the clot retention
      rate was significantly greater after M-TURP. CONCLUSION: Our results indicate
      that PK-TURP is equally as effective in the treatment of BPO, but has a more
      favorable safety profile in comparison to M-TURP. The clinical efficacy of PK
      TURP is long-lasting and comparable with M-TURP.

PMID- 22665340
TI  - Carriage rates and serogroups of Neisseria meningitidis among freshmen in a
      University dormitory in Korea.
AB  - PURPOSE: Neisseria meningitidis is a leading cause of bacterial meningitis in
      young adults. University students, especially those living in dormitories, have
      been known to be at increased risk of meningococcal disease. We performed a
      longitudinal study to determine the carriage rates of N. meningitidis and the
      changes thereof. MATERIALS AND METHODS: We recruited Inha University freshmen who
      were, at that time, admitted to a student dormitory. A pharyngeal swab was taken
      from all participant who were also asked to complete a questionnaire. This was
      repeated four weeks later. RESULTS: A total of 136 students were enrolled at the
      first culture. After four weeks, 128 students were enrolled, including 106 re
      participants. The overall carriage rates changed from 11.8% to 14.1%. In analysis
      of the 106 re-participants, "visiting to pubs" was associated with carriage of N.
      meningitis for both the first (p=0.047) and second cultures (p=0.026). Serogroup
      C was found to be the most frequent serogroup (5 isolates), while 3 isolates were
      found from serogroup B. The most prevalent PorA types were P1.22,14-6 (4
      isolates) and P1.19,15 (3 isolates). The DNA sequences of PorA VR2 were changed
      in 2 students during prolonged carriage. CONCLUSION: The meningococcal carriage
      rate among first year university students who resided in a dormitory did not
      significantly increase over 4-week interval between cultures, which is markedly
      different from those reported in Western studies. Close social contact appeared
      to be related with carriage. Our data also revealed diversity in PorA types,
      suggesting the possibility of rapid mutation of the PorA gene during the 4-week
      interval.

PMID- 22665341
TI  - Predicting factors of breakthrough infection in children with primary
      vesicoureteral reflux.
AB  - PURPOSE: Many pediatric urologists still favor using prophylactic antibiotics to
      treat children with vesicoureteral reflux (VUR). However, breakthrough infection
      sometimes occurs, leading to significant increases in morbidity as a result of
      renal scarring. Therefore, we tested whether abnormal renal scan and other
      factors are predictive of breakthrough infection using univariate analyses.
      MATERIALS AND METHODS: We retrospectively reviewed the medical records of 163
      consecutive children who were diagnosed with vesicoureteral reflux between
      November 1997 and June 2010. Clinical parameters for the statistical analysis
      included form of presentation, gender, age, VUR grade, laterality, presence of
      intrarenal reflux, class of antibiotic drug, and presence of abnormal renal scan
      by Dimercapto-succinic acid. Clinical parameters used for prognostic factors were
      established by univariate analyses. Fisher's exact test and unpaired t-test were
      done using SPSS software [SPSS ver. 12.0 (SPSS Inc., Chicago, IL, USA)]. RESULTS:
      Breakthrough infection developed in 61 children (48.0%). A total of 58 children
      (45.7%) had abnormal renal scans. Time to development of breakthrough infection
      was significantly longer in girls (9.0+/-8.2 months) than in boys (5.8+/-4.8
      months, p<0.05). On univariate analysis, though statistically not significant,
      the most predictive factor of breakthrough infection was abnormal renal scan
      (p=0.062). In patients with abnormal renal scans, breakthrough infection was not
      associated with mode of presentation, gender, grade or prophylactic antibiotics.
      However, there was a significant difference between patients younger than 1 year
      and those 1 year old or older. Mean+/-SD age at diagnosis of VUR in patients with
      breakthrough infection (1.14+/-3.14) was significantly younger than in those
      without breakthrough infection (5.05+/-3.31, p=0.009). There was also a
      significant difference between patients with bilateral or unilateral reflux
      (p=0.028). CONCLUSION: Our data showed that abnormal renal scan was the most
      predictive factor of breakthrough infection and demonstrated statistical
      significance in patients under the age of 1 year. Parents and physicians should
      remain aware that these patients are at high risk of breakthrough urinary tract
      infection, which may potentially lead to renal damage.

PMID- 22665342
TI  - Clinical features of Fitz-Hugh-Curtis Syndrome in the emergency department.
AB  - PURPOSE: Fitz-Hugh-Curtis Syndrome (FHCS) is a clinical entity characterized by
      inflammation of the liver capsule associated with genital tract infection. The
      aim of this study is to provide physicians with clinical suggestions for
      diagnostic approaches based on a series of patients who were diagnosed with FHCS.
      MATERIALS AND METHODS: We conducted a retrospective study of patients who were
      diagnosed with FHCS after presenting to the emergency department (ED). The
      symptoms, physical examinations, laboratory findings, radiological findings, and
      progress of the patients were reviewed. RESULTS: During the four-year study
      period, a total of 82 female patients received a final diagnosis of FHCS in the
      ED. Chlamydia trachomatis was identified as a pathogen in 89% of the patients.
      Their clinical characteristics and laboratory findings were described. Fifty-two
      patients (63.4%) were admitted to the hospital. All of the admitted patients
      improved after treatment combining antibiotic therapy with conservative care.
      CONCLUSION: FHCS should be considered as a differential diagnosis for female
      patients of childbearing age with right upper abdominal pain. Timely diagnosis
      using biphasic computed tomography (CT) with arterial and portal phases may help
      ensure adequate medical treatment as well as avoid invasive procedures.

PMID- 22665343
TI  - Anti-cyclic citrullinated peptide antibodies and joint involvement in Behcet's
      disease.
AB  - PURPOSE: We aimed to determine the prevalence of anti-cyclic citrullinated
      peptide (anti-CCP) antibodies in a large group of Korean patients with Behcet's
      disease (BD), with and without joint involvement, and to compare these findings
      with the prevalences of anti-CCP antibodies in patients with rheumatoid arthritis
      (RA) and systemic lupus erythematosus (SLE). MATERIALS AND METHODS: We tested 189
      patients with BD, 105 with RA, and 36 with SLE for anti-CCP antibodies and IgM
      rheumatoid factor in serum. We reviewed the medical records of patients with BD
      to investigate their personal and clinical characteristics as well as their
      laboratory test results. RESULTS: Anti-CCP antibodies were detected in seven of
      the 189 BD patients (3.7%), at a mean titer of 30.6+/-44.4 U/mL, in 86 of the 105
      RA patients (81.9%) with a mean titer of 198.8+/-205.7 U/mL, and in nine of the
      36 SLE patients (25%) with a mean titer of 180.4+/-113.9 U/mL. One of the seven
      anti-CCP-positive BD patients fulfilled the diagnostic criteria for both BD and
      RA. Five of the seven anti-CCP-positive BD patients (71.4%) had polyarticular
      joint involvement, and the other two patients (28.6%) had oligoarticular
      involvement. CONCLUSION: We determined the prevalence of anti-CCP antibodies in a
      large group of Korean BD patients with and without joint involvement. Negative
      anti-CCP test in patients with BD may help to differentiate BD from RA and SLE,
      all of which present with similar clinical features.

PMID- 22665344
TI  - Permissive hypotension in extremely low birth weight infants (<=1000 gm).
AB  - PURPOSE: We performed this study to evaluate the safety of permissive hypotension
      management in extremely low birth weight infants (ELBWIs). MATERIALS AND METHODS:
      Medical records of all inborn ELBWIs admitted to Samsung Medical Center from
      January 2004 to December 2008 were reviewed retrospectively. Of a total of 261
      ELBWIs, 47 (18%) required treatment for hypotension (group T), 110 (42%) remained
      normotensive (group N), and 104 (40%) experienced more than one episode of
      hypotension without treatment (group P) during the first 72 hours of life.
      Treatment of hypotension included inotropic support and/or fluid loading.
      RESULTS: Birth weight and Apgar scores were significantly lower in the T group
      than the other two groups. In the N group, the rate of pathologically confirmed
      maternal chorioamnionitis was significantly higher than other two groups, and the
      rate was higher in the P group than the T group. After adjusting for covariate
      factors, no significant differences in mortality and major morbidities were found
      between the N and P groups. However, the mortality rate and the incidence of
      intraventricular hemorrhage (>=stage 3) and bronchopulmonary dysplasia
      (>=moderate) were significantly higher in the T group than the other two groups.
      Long term neurodevelopmental outcomes were not significantly different between
      the N and P groups. CONCLUSION: Close observation of hypotensive ELBWIs who
      showed good clinical perfusion signs without intervention allowed to avoid
      unnecessary medications and resulted in good neurological outcomes.

PMID- 22665345
TI  - Predictors of postoperative mortality of ruptured abdominal aortic aneurysm: a
      retrospective clinical study.
AB  - PURPOSE: Despite significant improvements in surgery, anesthesia, and
      postoperative critical care, the postoperative mortality rate of ruptured
      abdominal aortic aneurysm (RAAA) has remained at 40% to 50% for several decades.
      Therefore, we evaluated factors associated with the postoperative mortality of
      RAAA. MATERIALS AND METHODS: From January 1999 to December 2008, a retrospective
      study was performed with 34 patients who underwent open repair of RAAA. The
      preoperative factors included age, sex, smoking, comorbidities, serum creatinine,
      hemoglobin, shock, pulse rate, and time from emergency room to operation room.
      The intraoperative factors included blood loss, transfusion, aortic clamping site
      and time, aneurysmal characteristics, rupture type, graft type, hourly urine
      output (HUO), and operative time. The postoperative factors included inotropic
      support, renal replacement therapy (RRT), reoperation, bowel ischemia, multiple
      organ failure (MOF), and intensive care unit stay. The 2-day and the 30-day
      mortality rates were analyzed separately. RESULTS: The 2-day and the 30-day
      mortality rates were 14.7% and 41.2%, respectively. On univariate analysis,
      shock, transfusion, HUO, inotropic support and MOF for the 2-day mortality and
      serum creatinine, transfusion, aortic clamping site, HUO, inotropic support, RRT
      and MOF for the 30-day mortality were statistically significant. On multivariate
      analysis, shock, inotropic support and MOF for the 2-day mortality and aortic
      clamping site, RRT and MOF for the 30-day mortality were statistically
      significant. CONCLUSION: To decrease the postoperative mortality rate of RAAA,
      prevention of massive hemorrhage and acute renal failure with infrarenal aortic
      clamping, as well as prompt operative control of bleeding and maintenance of
      systemic perfusion are important.

PMID- 22665346
TI  - Acute appendicitis in children with acute leukemia: experiences of a single
      institution in Korea.
AB  - PURPOSE: Acute appendicitis has been reported to be relatively rare in pediatric
      leukemia patients but there is no official data for this in Korea. And there is
      no consensus for its treatment in this population. MATERIALS AND METHODS: We
      conducted a retrospective study of 7 patients diagnosed with appendicitis among
      1209 pediatric patients who were diagnosed with leukemia from 1996 to 2008 at a
      single institution in Korea. RESULTS: The median age at the time of the diagnosis
      of appendicitis was 12 years (range: 3-15 years), and 3 of the patients were
      male. The median absolute neutrophil count (ANC) at the time of diagnosis was
      0.99*109/L (range: 0-3*109/L). The mean time from the onset of symptoms to the
      diagnosis was 4 days. All 7 leukemia patients with appendicitis underwent surgery
      and they demonstrated a survival of 100% without significant complications.
      CONCLUSION: The incidence of appendicitis in pediatric leukemia patients was
      0.57% in our study. Early diagnosis with abdominal ultrasound or computed
      tomography and early surgical resection in leukemic patient with acute
      appendicitis may be a safer and more effective treatment option. Even when
      perforation has already occurred and when the patient has an ANC of 0*109/L,
      surgical treatment may improve overall survival without incurring significant
      complications.

PMID- 22665347
TI  - Transdermal fentanyl for chronic low back pain.
AB  - PURPOSE: Chronic low back pain is a common clinical problem. As medication, non
      steroidal anti-inflammatory drugs are generally used; however, they are sometimes
      non-effective. Recently, opioids have been used for the treatment of chronic low
      back pain, and since 2010, transdermal fentanyl has been used to treat chronic
      non-cancer pain in Japan. The purpose of the current study was to examine the
      efficacy of transdermal fentanyl in the treatment of chronic low back pain.
      MATERIALS AND METHODS: This study included patients (n=62) that suffered from
      chronic low back pain and were non-responsive to non-steroidal anti-inflammatory
      drugs. Their conditions consisted of non-specific low back pain, multiple back
      operations, and specific low back pain awaiting surgery. Patients were given
      transdermal fentanyl for chronic low back pain. Scores of the visual analogue
      scale and the Oswestry Disability Index, as well as adverse events were evaluated
      before and after therapy. RESULTS: Overall, visual analogue scale scores and
      Oswestry Disability Index scores improved significantly after treatment.
      Transdermal fentanyl (12.5 to 50 MUg/h) was effective in reducing low back pain
      in 45 of 62 patients; however, it was not effective in 17 patients. Patients who
      experienced the most improvement were those with specific low back pain awaiting
      surgery. Adverse events were seen in 40% of patients (constipation, 29%; nausea,
      24%; itching, 24%). CONCLUSION: Transdermal fentanyl significantly improved
      visual analog scale scores and Oswestry Disability Index scores in 73% of
      patients, especially those with specific low back pain awaiting surgery; however,
      it did not decrease pain in 27% of patients, including patients with non-specific
      low back pain or multiple back operations.

PMID- 22665348
TI  - Evaluation of postoperative range of motion and functional outcomes after
      cruciate-retaining and posterior-stabilized high-flexion total knee arthroplasty.
AB  - PURPOSE: The purpose of this study was to compare postoperative range of motion
      and functional outcomes among patients who received high-flexion total knee
      arthroplasty using cruciate-retaining (CR-Flex) and posterior-stabilized (PS
      Flex) type prostheses. MATERIALS AND METHODS: Among 127 patients (186 knees) who
      underwent high-flexion total knee arthroplasty between 2005 and 2007, 92 knees
      were placed in the CR-Flex group, and 94 knees were placed in the PS-Flex group.
      After two years of postoperative follow-up, clinical and radiographic data were
      reviewed. Postoperative non-weight-bearing range of knee motion, angle of flexion
      contracture and functional outcomes based on the Western Ontario and McMaster
      Universities Osteoarthritis (WOMAC) functional sub-scale were assessed and
      compared between the two groups. RESULTS: After the 2-year postoperative period,
      the mean range of motion was 131 degrees  in the CR-Flex group and 133 degrees 
      in the PS-Flex group. There were no significant differences in postoperative
      range of motion between the two groups. Only age at operation and preoperative
      range of motion were significantly associated with postoperative range of motion
      after high-flexion total knee arthroplasty. Postoperative functional outcomes
      based on the WOMAC functional sub-scale were slightly better in the CR-Flex group
      (9.2+/-9.1 points) than in the PS-Flex group (11.9+/-9.6 points); however, this
      difference was not statistically significant (p=non-significant). CONCLUSION: The
      retention or substitution of the posterior cruciate ligament does not affect
      postoperative range of motion (ROM) or functional outcomes, according to 2 years
      of postoperative follow-up of high-flexion total knee arthroplasty.

PMID- 22665350
TI  - Parent-reported symptoms of attention deficit hyperactivity disorder in children
      with intermittent exotropia before and after strabismus surgery.
AB  - PURPOSE: To investigate the symptoms of attention deficit hyperactivity disorder
      (ADHD) as reported by parents in children with intermittent exotropia [X(T)] and
      to determine whether strabismus surgery for X(T) affects ADHD symptoms. MATERIALS
      AND METHODS: Fifty-one consecutive children undergoing muscle surgery for X(T)
      were prospectively recruited. One parent of each child completed the ADHD rating
      scale IV (ADHD RS-IV) assessment consecutively before and one year after surgery.
      Patients whose preoperative scores were above the cut-off point, the 90th
      percentile based on a Korean sample, were regarded as demonstrating the ADHD
      trait. The impact of muscle surgery on ADHD symptoms was assessed by comparing
      the preoperative scores with the post-operative scores. RESULTS: Eight (15.7%) of
      the 51 patients demonstrated the ADHD trait. ADHD RS-IV scores following
      strabismus surgery significantly decreased in patients with the ADHD trait
      (p=0.014), while they did not differ in patients without the ADHD trait. Seven
      (87.5%) of the 8 patients with the ADHD trait showed improvement in their ADHD RS
      IV scores after surgery. There was no difference in surgical success rates
      between X(T) patients with and without the ADHD trait. CONCLUSION: The ADHD trait
      was relatively common in children with X(T), and the parent-reported symptoms of
      the children with the ADHD trait improved after strabismus surgery. These results
      suggest that childhood X(T) may be one contributing factor to ADHD- related
      symptoms.

PMID- 22665349
TI  - Existence of a neuropathic pain component in patients with osteoarthritis of the
      knee.
AB  - PURPOSE: Pain from osteoarthritis (OA) is generally classified as nociceptive
      (inflammatory). Animal models of knee OA have shown that sensory nerve fibers
      innervating the knee are significantly damaged with destruction of subchondral
      bone junction, and induce neuropathic pain (NP). Our objective was to examine NP
      in the knees of OA patients using painDETECT (an NP questionnaire) and to
      evaluate the relationship between NP, pain intensity, and stage of OA. MATERIALS
      AND METHODS: Ninety-two knee OA patients were evaluated in this study. Pain
      scores using Visual Analogue Scales (VAS), Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC), painDETECT, duration of symptoms,
      severity of OA using the Kellgren-Lawrence (KL) system, and amount of joint fluid
      were evaluated and compared using a Spearman's correlation coefficient by rank
      test. RESULTS: Our study identified at least 5.4% of our knee OA patients as
      likely to have NP and 15.2% as possibly having NP. The painDETECT score was
      significantly correlated with the VAS and WOMAC pain severity. Compared with the
      painDETECT score, there was a tendency for positive correlation with the KL
      grade, and tendency for negative correlation with the existence and amount of
      joint fluid, but these correlations were not significant. CONCLUSION: PainDETECT
      scores classified 5.4% of pain from knee OA as NP. NP tended to be seen in
      patients with less joint fluid and increased KL grade, both of which corresponded
      to late stages of OA. It is important to consider the existence of NP in the
      treatment of knee OA pain.

PMID- 22665351
TI  - Mixed echoic thyroid nodules on ultrasound: approach to management.
AB  - PURPOSE: To evaluate malignancy risk according to ultrasound (US) features and
      size change on follow-up US in mixed echoic thyroid nodules and to suggest
      management guidelines thereof. MATERIALS AND METHODS: Among patients who
      underwent US-guided fine needle aspiration biopsy, 316 mixed echoic nodules in
      303 patients were included after excluding the patients with pure solid or cystic
      nodules or without further cytopathologic evaluation. We evaluated malignancy
      risk according to US features and changes in size and shape on follow-up US.
      RESULTS: The malignancy rate was 31.6% (6 of 19) for nodules with suspicious US
      features and 2.7% (8 of 297) for nodules without suspicious US features
      (p<0.001). Among 265 nodules with no suspicious US features and initial benign
      cytology, 15 nodules with suspicious US change and decreased size, 25 nodules
      with no suspicious US change and increased size, and 225 nodules with no
      suspicious US change and no change in size were observed on follow-up USs. The
      malignancy risk thereof was 0%, 0% and 0.4%, respectively (p=1.000). CONCLUSION:
      Mixed echoic nodules with no suspicious US features and benign cytology can be
      followed up using US, as they revealed very low malignancy rates, even if they
      showed growth on follow-up US.

PMID- 22665352
TI  - Magnetic resonance arthrographic dissection of posterolateral corner of the knee:
      revealing the meniscofibular ligament.
AB  - PURPOSE: To evaluate meniscofibular ligament (MFibL) at the posterolateral corner
      of the knee joint on the magnetic resonance arthrography (MRA) with 70 degrees 
      knee flexion. MATERIALS AND METHODS: The MRA of the knee joint was performed at
      70 degrees  knee flexion. Eighteen patients (19 knee joints) underwent scanning
      of sagittal, coronal, and axial fat-suppressed T1 weighted images (T1FS), and
      coronal fat-suppressed T2 weighted images. Sagittal three-dimensional (3D)
      gradient echo (GRE) images were also obtained. Retrospective review of 19 knee
      MRA studies was independently performed by two musculoskeletal radiologists. The
      statistical significance was proved by chi-square test. RESULTS: The MFibL
      ligament was optimally demonstrated on the far lateral sagittal 3D GRE and T1FS
      MRA images. The MFibL appeared as a curvilinear or straight hypointense band of
      variable thickness, extended from the posterolateral meniscus to upper
      anteromedial aspect of the fibular head. The MFibL was demonstrated with scale 2
      (more than a half length of the ligament) by both reviewers in 73.68% (n=14/19)
      of the knee 3D GRE images and 89.47% (n=17/19) of the knee T1FS images. The
      visualization on T1FS and that on GRE were not statistically different from each
      other (p>0.05). The interobserver agreements were significantly good on both 3D
      GRE and T1FS images in detecting the ligament (kappa values, 0.642 and 0.683,
      respectively). CONCLUSION: The MFibL is well visualized on the far lateral
      sagittal MRA at 70 degrees  knee flexion, which could potentially be useful in
      recognizing structures in the posterolateral corner of the knee, including the
      MFibL.

PMID- 22665353
TI  - Diffusion-weighted MR imaging before and after contrast enhancement with
      superparamagnetic iron oxide for assessment of hepatic metastasis.
AB  - PURPOSE: The purpose of our study was to validate diffusion-weighted MRI (DWI)
      before and after superparamagnetic iron oxide (SPIO) injection for assessment of
      hepatic metastases. MATERIALS AND METHODS: Eighty-six hepatic metastases (size
      range, 0.3-4.7 cm; mean, 1.5 cm) verified pathologically or by follow-up imaging
      studies in 22 consecutive patients (17 men and 5 women; 44-83 years; mean age, 60
      years) during a 13-month period were enrolled. Hepatic MRI, including DWI (b
      factors=50, 400, 800 s/mm2) with breath-holding technique of single-shot spin
      echo echo-planar imaging (TR/TE=1000/69 ms, average=2) before and after SPIO
      administration, were retrospectively reviewed by two independent radiologists
      with a 5-point scale confidence score for each hepatic lesion on pre-contrast DWI
      (pre-DWI), SPIO-enhanced DWI (SPIO-DWI), and SPIO-enhanced T2*-weighted imaging
      (SPIO-T2*wI). RESULTS: For all lesions, SPIO-T2*wI showed significantly higher
      confidence score in the diagnosis of hepatic metastases than pre-contrast or SPIO
      DWI regardless of the size of b-factors (p<0.05) with only one exception; using b
      factor=50 s/mm2, the score of SPIO-T2*wI was still higher than SPIO-DWI but there
      was no statistical significance given by observer 1 (p=0.730). For the
      subcentimeter lesions (n=37), SPIO-T2*wI showed the highest score, and using b
      factor= 50 or 400 s/mm2 SPIO-DWI showed similar confidence scores to SPIO-T2*wI
      by both observers (p>0.05). Pre-DWI using b-factor=50 sec/mm2 was also comparable
      with SPIO-T2*wI by observer 1 (p=0.060). CONCLUSION: Pre-DWI has a limited value
      for the assessment of hepatic metastases, however, the repetition of DWI after
      SPIO injection using small b-factors could complement SPIO-T2*wI, especially for
      subcentimeter lesions.

PMID- 22665354
TI  - Capsaicin-induced apoptosis of FaDu human pharyngeal squamous carcinoma cells.
AB  - PURPOSE: To investigate the anti-tumor effect of capsaicin on human pharyngeal
      squamous carcinoma cells (FaDu). MATERIALS AND METHODS: The expression of
      apoptosis/cell cycle-related proteins (or genes) was examined by reverse
      transcriptase- polymerase chain reaction, western blotting and ELISA methods,
      while the apoptotic cell population, cell morphology and DNA fragmentation levels
      were assessed using flow cytometry, fluorescence microscopy and agarose gel
      electrophoresis. RESULTS: Capsaicin was found to inhibit the growth and
      proliferation of FaDu cells in a dose- and time-dependent manner. Apoptotic cell
      death was confirmed by observing increases in nuclear condensation, nuclear DNA
      fragmentation and sub-G1 DNA content. The observed increase in cytosolic
      cytochrome c, activation of caspase 3 and PARP (p85) levels following capsaicin
      treatment indicated that the apoptotic response was mitochondrial pathway
      dependent. Gene/protein expression analysis of Bcl-2, Bad and Bax further
      revealed decreased anti-apoptotic Bcl-2 protein and increased pro-apoptotic
      Bad/Bax expression. Furthermore, capsaicin suppressed the cell cycle progression
      at the G1/S phase in FaDu cells by decreasing the expression of the regulators of
      cyclin B1 and D1, as well as cyclin-dependent protein kinases cdk-1, cdk-2 and
      cdk-4. CONCLUSION: Our current data show that capsaicin induces apoptosis in FaDu
      cells and this response is associated with mitochondrial pathways, possibly by
      mediating cell cycle arrest at G1/S.

PMID- 22665355
TI  - Fluoxetine protects against big endothelin-1 induced anti-apoptosis by rescuing
      Kv1.5 channels in human pulmonary arterial smooth muscle cells.
AB  - PURPOSE: Pulmonary Kv channels are thought to play a crucial role in the
      regulation of cell proliferation and apoptosis. Previous studies have shown that
      fluoxetine upregulated the expression of Kv1.5 and prevented pulmonary arterial
      hypertension in monocrotaline-induced or hypoxia-induced rats and mice. The
      current study was designed to test how fluoxetine regulates Kv1.5 channels,
      subsequently promoting apoptosis in human PASMCs cultured in vitro. MATERIALS AND
      METHODS: Human PASMCs were incubated with low-serum DMEM, ET-1, and fluoxetine
      with and without ET-1 separately for 72 h. Then the proliferation, apoptosis, and
      expression of TRPC1 and Kv1.5 were detected. RESULTS: In the ET-1 induced group,
      the upregulation of TRPC1 and down regulation of Kv1.5 enhanced proliferation and
      anti-apoptosis, which was reversed when treated with fluoxetine. The decreased
      expression of TRPC1 increased the expression of Kv1.5, subsequently inhibiting
      proliferation while promoting apoptosis. CONCLUSION: The results from the present
      study suggested that fluoxetine protects against big endothelin-1 induced anti
      apoptosis and rescues Kv1.5 channels in human pulmonary arterial smooth muscle
      cells, potentially by decreasing intracellular concentrations of Ca2+.

PMID- 22665356
TI  - Anococcygeal raphe revisited: a histological study using mid-term human fetuses
      and elderly cadavers.
AB  - PURPOSE: We recently demonstrated the morphology of the anococcygeal ligament. As
      the anococcygeal ligament and raphe are often confused, the concept of the
      anococcygeal raphe needs to be re-examined from the perspective of fetal
      development, as well as in terms of adult morphology. MATERIALS AND METHODS: We
      examined the horizontal sections of 15 fetuses as well as adult histology. From
      cadavers, we obtained an almost cubic tissue mass containing the dorsal wall of
      the anorectum, the coccyx and the covering skin. Most sections were stained with
      hematoxylin and eosin or Masson-trichrome solution. RESULTS: The adult ligament
      contained both smooth and striated muscle fibers. A similar band-like structure
      was seen in fetuses, containing: 1) smooth muscle fibers originating from the
      longitudinal muscle coat of the anal canal and 2) striated muscle fibers from the
      external anal sphincter (EAS). However, in fetuses, the levator ani muscle did
      not attach to either the band or the coccyx. Along and around the anococcygeal
      ligament, we did not find any aponeurotic tissue with transversely oriented
      fibers connecting bilateral levator ani slings. Instead, in adults, a fibrous
      tissue mass was located at a gap between bilateral levator ani slings; this site
      corresponded to the dorsal side of the ligament and the EAS in the immediately
      deep side of the natal skin cleft. CONCLUSION: We hypothesize that a classically
      described raphe corresponds to the specific subcutaneous tissue on the
      superficial or dorsal side of the anococcygeal ligament.

PMID- 22665357
TI  - A case of acute disseminated encephalomyelitis associated with hepatitis C virus
      infection.
AB  - Acute disseminated encephalomyelitis (ADEM) is a monophasic autoimmune
      demyelinating disease of the central nervous system, which typically follows
      acute viral or bacterial infection or vaccination. We report a case of ADEM
      associated with hepatitis C virus (HCV) infection with positive serum and
      cerebrospinal fluid (CSF) anti-HCV antibody. After steroid treatment, neurologic
      symptoms were improved. Virus triggers autoimmunity or direct viral invasion
      plays a part in the genesis of ADEM. This is the first reported case of ADEM with
      anti-HCV antibody in the CSF.

PMID- 22665358
TI  - Cerebral salt wasting treated with fludrocortisone in a 17-year-old boy.
AB  - Cerebral salt wasting is characterized by inappropriate natriuresis and volume
      contraction with associated cerebral pathology. It is distinct from the syndrome
      of inappropriate antidiuretic hormone secretion, which is characterized by
      inappropriate retention of free water. We report a patient with a porencephalic
      cyst who developed cerebral salt wasting. His initial treatment was
      supplementation of water and salt, which did not improve natriuresis or volume
      contraction. Fludrocortisone administration effectively managed the cerebral salt
      wasting.

PMID- 22665359
TI  - Oral muscle relaxant may induce immediate allergic reactions.
AB  - Eperisone and afloqualone act by relaxing both skeletal and vascular smooth
      muscles to improve circulation and suppress pain reflex. These drugs are
      typically prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) as
      painkillers. However, there have been no reports on serious adverse reactions to
      oral muscle relaxants; and this is the first report to describe three allergic
      reactions caused by eperisone and afloqualone. All three patients had histories
      of allergic reactions after oral intake of multiple painkillers, including oral
      muscle relaxants and NSAIDs, for chronic muscle pain. An open-label oral
      challenge test was performed with each drug to confirm which drugs caused the
      systemic reactions. All patients experienced the same reactions within one hour
      after oral intake of eperisone or afloqualone. The severity of these reactions
      ranged from laryngeal edema to hypotension. To confirm that the systemic reaction
      was caused by eperisone or afloqualone, skin prick testing and intradermal skin
      tests were performed with eperisone or afloqualone extract in vivo, and basophil
      activity tests were performed after stimulation with these drugs in vitro. In one
      patient with laryngeal edema, the intradermal test with afloqualone extract had a
      positive result, and CD63 expression levels on basophils increased in a dose
      dependent manner by stimulation with afloqualone. We report three allergic
      reactions caused by oral muscle relaxants that might be mediated by non
      immunoglobulin E-mediated responses. Since oral muscle relaxants such as
      eperisone and afloqualone are commonly prescribed for chronic muscle pain and can
      induce severe allergic reactions, we should prescribe them carefully.

PMID- 22665360
TI  - Re: microalbuminuria in normal Korean children.

PMID- 22665361
TI  - Clinical usefulness of a rapid antigen test in patients with 2009 H1N1 influenza.

PMID- 22665363
TI  - Fuel, electricity, ER and HER2--a hybrid-car model of breast cancer.

PMID- 22665364
TI  - Haematological cancer: Lenalidomide maintenance--perils of a premature
      denouement.

PMID- 22665365
TI  - Urological cancer: For localized prostate cancer, does technology equal progress?

PMID- 22665366
TI  - Elevated urinary levels of kidney injury molecule-1 among Chinese factory workers
      exposed to trichloroethylene.
AB  - Epidemiological studies suggest that trichloroethylene (TCE) exposure may be
      associated with renal cancer. The biological mechanisms involved are not exactly
      known although nephrotoxicity is believed to play a role. Studies on TCE
      nephrotoxicity among humans, however, have been largely inconsistent. We studied
      kidney toxicity in Chinese factory workers exposed to TCE using novel sensitive
      nephrotoxicity markers. Eighty healthy workers exposed to TCE and 45 comparable
      unexposed controls were included in the present analyses. Personal TCE exposure
      measurements were taken over a 2-week period before urine collection. Ninety-six
      percent of workers were exposed to TCE below the current US Occupational Safety
      and Health Administration permissible exposure limit (100 ppm 8h TWA), with a
      mean (SD) of 22.2 (35.9) ppm. Kidney injury molecule-1 (KIM-1) and Pi-glutathione
      S transferase (GST) alpha were elevated among the exposed subjects as compared
      with the unexposed controls with a strong exposure-response association between
      individual estimates of TCE exposure and KIM-1 (P < 0.0001). This is the first
      report to use a set of sensitive nephrotoxicity markers to study the possible
      effects of TCE on the kidneys. The findings suggest that at relatively low
      occupational exposure levels a toxic effect on the kidneys can be observed. This
      finding supports the biological plausibility of linking TCE exposure and renal
      cancer.

PMID- 22665367
TI  - Systematic evaluation of apoptotic pathway gene polymorphisms and lung cancer
      risk.
AB  - We adopted a two-stage study design to screen 927 single nucleotide polymorphisms
      (SNPs) located in 73 apoptotic-pathway genes in a case-control study and then
      performed a fast-track validation of the significant SNPs in a replication
      population to identify sequence variations in the apoptotic pathway modulating
      lung cancer risk. Fifty-five SNPs showed significant associations in the
      discovery population comprised of 661 lung cancer cases and 959 controls. Six of
      these SNPs located in three genes (Bcl-2, CASP9 and ANKS1B) were validated in a
      replication population with 1154 cases and 1373 controls. Additive model was the
      best-fitting model for five SNPs (rs1462129 and rs255102 of Bcl-2, rs6685648 of
      CASP9 and rs1549102, rs11110099 of ANKS1B) and recessive model was the best fit
      for one SNP (rs10745877 of ANKS1B). In the analysis of joint effects with
      subjects carrying no unfavorable genotypes as the reference group, those carrying
      one, two, and three or more unfavorable genotypes had an odds ratio (OR) of 2.22
      [95% confidence interval (CI) = 1.08-4.57, P = 0.03], 2.70 (95% CI = 1.33-5.49; P
      = 0.006) and 4.13 (95% CI = 2.00-8.57; P = 0.0001), respectively (P for trend =
      6.05E-06). The joint effect of unfavorable genotypes was also validated in the
      replication population. The SNPs identified are located in or near key genes
      known to play important roles in apoptosis regulation, supporting the strong
      biological relevance of our findings. Future studies are needed to identify the
      causal SNPs and elucidate the underlying molecular mechanisms.

PMID- 22665369
TI  - Nuclear localization signal in a cancer-related transcriptional regulator protein
      NAC1.
AB  - Nucleus accumbens-associated protein 1 (NAC1) might have potential oncogenic
      properties and participate in regulatory networks for pluripotency. Although NAC1
      is described as a transcriptional regulator, the nuclear import machinery of NAC1
      remains unclear. We found, using a point mutant, that dimer formation was not
      committed to the nuclear localization of NAC1 and, using deletion mutants, that
      the amino-terminal half of NAC1 harbored a potential nuclear localization signal
      (NLS). Wild type, but not mutants of this region, alone was sufficient to drive
      the importation of green fluorescent protein (GFP) into the nucleus. Bimax1, a
      synthetic peptide that blocks the importin alpha/beta pathway, impaired nuclear
      localization of NAC1 in cells. We also used the binding properties of importin to
      demonstrate that this region is an NLS. Furthermore, the transcriptional
      regulator function of NAC1 was dependent on its nuclear localization activity in
      cells. Taken together, these results show that the region with a bipartite motif
      constitutes a functional nuclear import sequence in NAC1 that is independent of
      NAC1 dimer formation. The identification of an NAC1 NLS thus clarifies the
      mechanism through which NAC1 translocates to the nucleus to regulate the
      transcription of genes involved in oncogenicity and pluripotency.

PMID- 22665368
TI  - Sex-specific association of sequence variants in CBS and MTRR with risk for
      promoter hypermethylation in the lung epithelium of smokers.
AB  - Gene promoter hypermethylation is now regarded as a promising biomarker for the
      risk and progression of lung cancer. The one-carbon metabolism pathway is
      postulated to affect deoxyribonucleic acid (DNA) methylation because it is
      responsible for the generation of S-adenosylmethionine (SAM), the methyl donor
      for cellular methylation reactions. This study investigated the association of
      single nucleotide polymorphisms (SNPs) in six one-carbon metabolism-related genes
      with promoter hypermethylation in sputum DNA from non-Hispanic white smokers in
      the Lovelace Smokers Cohort (LSC) (n = 907). Logistic regression was used to
      assess the association of SNPs with hypermethylation using a high/low methylation
      cutoff. SNPs in the cystathionine beta synthase (CBS) and 5
      methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) genes were
      significantly associated with high methylation in males [CBS rs2850146 (-8283G >
      C), OR = 4.9; 95% CI: 1.98, 12.2, P = 0.0006] and low methylation in females
      [MTRR rs3776467 (7068A > G), OR = 0.57, 95% CI: 0.42, 0.77, P = 0.0003]. The
      variant allele of rs2850146 was associated with reduced gene expression and
      increased plasma homocysteine (Hcy) concentrations. Three plasma metabolites,
      Hcy, methionine and dimethylglycine, were associated with increased risk for gene
      methylation. These studies suggest that SNPs in CBS and MTRR have sex-specific
      associations with aberrant methylation in the lung epithelium of smokers that
      could be mediated by the affected one-carbon metabolism and transsulfuration in
      the cells.

PMID- 22665370
TI  - Congenital and acquired heart disease converge: ischaemic heart disease with a
      background of scimitar syndrome.

PMID- 22665371
TI  - Statins: pleiotropic, but less than previously thought.

PMID- 22665372
TI  - Multimodal imaging of anomalous pulmonary venous return in an adult patient with
      Scimitar syndrome.

PMID- 22665373
TI  - Surgical recycling of a percutaneously implanted Melody valve.

PMID- 22665374
TI  - Unique biological activity of botulinum D/C mosaic neurotoxin in murine species.
AB  - Clostridium botulinum types C and D cause animal botulism by the production of
      serotype-specific or mosaic botulinum neurotoxin (BoNT). The D/C mosaic BoNT
      (BoNT/DC), which is produced by the isolate from bovine botulism in Japan,
      exhibits the highest toxicity to mice among all BoNTs. In contrast, rats appeared
      to be very resistant to BoNT/DC in type C and D BoNTs and their mosaic BoNTs. We
      attempted to characterize the enzymatic and receptor-binding activities of
      BoNT/DC by comparison with those of type C and D BoNTs (BoNT/C and BoNT/D).
      BoNT/DC and D showed similar toxic effects on cerebellar granule cells (CGCs)
      derived from the mouse, but the former showed less toxicity to rat CGCs. In
      recombinant murine-derived vesicle-associated membrane protein (VAMP), the
      enzymatic activities of both BoNTs to rat isoform 1 VAMP (VAMP1) were lower than
      those to the other VAMP homologues. We then examined the physiological
      significance of gangliosides as the binding components for types C and D, and
      mosaic BoNTs. BoNT/DC and C were found to cleave an intracellular substrate of
      PC12 cells upon the exogenous addition of GM1a and GT1b gangliosides,
      respectively, suggesting that each BoNT recognizes a different ganglioside
      moiety. The effect of BoNT/DC on glutamate release from CGCs was prevented by
      cholera toxin B-subunit (CTB) but not by a site-directed mutant of CTB that did
      not bind to GM1a. Bovine adrenal chromaffin cells appeared to be more sensitive
      to BoNT/DC than to BoNT/C and D. These results suggest that a unique mechanism of
      receptor binding of BoNT/DC may differentially regulate its biological activities
      in animals.

PMID- 22665375
TI  - Distinguishing the contribution of type 1 pili from that of other QseB
      misregulated factors when QseC is absent during urinary tract infection.
AB  - Urinary tract infections (UTI), primarily caused by uropathogenic Escherichia
      coli (UPEC), are one of the leading bacterial infections due to their high
      frequency and rate of recurrence. Both type 1 pilus adhesive organelles (fim) and
      the QseC sensor kinase have been implicated in UPEC virulence during UTI and have
      been individually reported to be promising drug targets. Deletion of qseC leads
      to pleiotropic effects due to unregulated activation of the cognate response
      regulator QseB, influencing conserved metabolic processes and diminishing
      expression of virulence genes, including type 1 pili. Here, we discern the type 1
      pilus-dependent and -independent effects that contribute to the virulence
      attenuation of a UPEC qseC deletion mutant in a murine model of experimental UTI.
      We show that although a DeltaqseC mutant restored for type 1 pilus expression
      regains the ability to colonize the host and initiate acute infection up to 16 h
      postinfection, it is rapidly outcompeted during acute infection when coinoculated
      with a wild-type strain. As a result, this strain has a diminished capacity to
      establish chronic infection. A prophylactic oral dose of a FimH small-molecular
      weight antagonist (ZFH-02056) further reduced the ability of the qseC mutant to
      establish chronic infection. Thus, loss of QseC significantly enhances the
      efficacy of ZFH-02056. Collectively, our work indicates that type 1 pili and QseC
      become critical in different infection stages, and that dual targeting of these
      factors has an additive effect on ablating UPEC virulence.

PMID- 22665376
TI  - Decreased expression of type 1 fimbriae by a pst mutant of uropathogenic
      Escherichia coli reduces urinary tract infection.
AB  - The pstSCAB-phoU operon encodes the phosphate-specific transport system (Pst).
      Loss of Pst constitutively activates the Pho regulon and decreases bacterial
      virulence. However, specific mechanisms underlying decreased bacterial virulence
      through inactivation of Pst are poorly understood. In uropathogenic Escherichia
      coli (UPEC) strain CFT073, inactivation of pst decreased urinary tract
      colonization in CBA/J mice. The pst mutant was deficient in production of type 1
      fimbriae and showed decreased expression of the fimA structural gene which
      correlated with differential expression of the fimB, fimE, ipuA, and ipbA genes,
      encoding recombinases, mediating inversion of the fim promoter. The role of fim
      downregulation in attenuation of the pst mutant was confirmed using a fim phase
      locked-on derivative, which demonstrated a significant gain in virulence. In
      addition, the pst mutant was less able to invade human bladder epithelial cells.
      Since type 1 fimbriae contribute to UPEC virulence by promoting colonization and
      invasion of bladder cells, the reduced bladder colonization by the pst mutant is
      predominantly attributed to downregulation of these fimbriae. Elucidation of
      mechanisms mediating the control of type 1 fimbriae through activation of the Pho
      regulon in UPEC may open new avenues for therapeutics or prophylactics against
      urinary tract infections.

PMID- 22665377
TI  - Staphylococcal superantigen-like protein 3 binds to the Toll-like receptor 2
      extracellular domain and inhibits cytokine production induced by Staphylococcus
      aureus, cell wall component, or lipopeptides in murine macrophages.
AB  - Staphylococcal superantigen-like proteins (SSLs) are a family of exoproteins
      sharing structural similarity with superantigens, but no superantigenic activity.
      Corresponding host target proteins or receptors against a portion of SSLs in the
      family have been identified. In this study, we show that SSL3 specifically binds
      to Toll-like receptor 2 (TLR2) and inhibits the stimulation of macrophages by
      TLR2 ligands. An approximately 100-kDa protein was recovered by using recombinant
      His-tagged SSL3-conjugated Sepharose from the lysate of porcine spleen, and the
      protein was identified as porcine TLR2 by peptide mass fingerprinting analysis.
      The SSL3-conjugated Sepharose recovered human and mouse TLR2 but not TLR4 from
      human neutrophils and mouse macrophage RAW 264.7 cells, as well as a recombinant
      TLR2 extracellular domain chimera protein. The production levels of interleukin
      12 (IL-12) from mouse macrophages treated with heat-killed Staphylococcus aureus
      and of tumor necrosis factor alpha (TNF-alpha) from RAW 264.7 cells induced by
      peptidoglycan or lipopeptide TLR2 ligands were strongly suppressed in the
      presence of SSL3. The mutation of consensus sialic acid-containing glycan-binding
      residues in SSL3 did not abrogate the binding ability to TLR2 or inhibitory
      activity on TLR2, indicating that the interaction of SSL3 with TLR2 was
      independent of the sialic acid-containing glycan-binding residues. These findings
      demonstrate that SSL3 is able to bind the extracellular domain of TLR2 and
      interfere with TLR2 function. The present study provides a novel mechanism of
      SSL3 in immune evasion of S. aureus via interfering with its recognition by
      innate immune cells.

PMID- 22665378
TI  - Alveolar macrophages in neonatal mice are inherently unresponsive to Pneumocystis
      murina infection.
AB  - Pneumocystis pneumonia was first diagnosed in malnourished children and has more
      recently been found in children with upper respiratory symptoms. We previously
      reported that there is a significant delay in the immune response in newborn mice
      infected with Pneumocystis compared to adults (Garvy BA, Harmsen AG, Infect.
      Immun. 64:3987-3992, 1996, and Garvy BA, Qureshi M, J. Immunol. 165:6480-6486,
      2000). This delay is characterized by the failure of neonatal lungs to upregulate
      proinflammatory cytokines and attract T cells into the alveoli. Here, we report
      that regardless of the age at which we infected the mice, they failed to mount an
      inflammatory response in the alveolar spaces until they were 21 days of age or
      older. Anti-inflammatory cytokines had some role in dampening inflammation, since
      interleukin-10 (IL-10)-deficient pups cleared Pneumocystis faster than wild-type
      pups and the neutralization of transforming growth factor beta (TGF-beta) with
      specific antibody enhanced T cell migration into the lungs at later time points.
      However, the clearance kinetics were similar to those of control pups, suggesting
      that there is an intrinsic deficiency in the ability of innate immunity to
      control Pneumocystis. We found, using an adoptive transfer strategy, that the
      lung environment contributes to association of Pneumocystis organisms with
      alveolar macrophages, implying no intrinsic deficiency in the binding of
      Pneumocystis by neonatal macrophages. Using both in vivo and in vitro assays, we
      found that Pneumocystis organisms were less able to stimulate translocation of NF
      kappaB to the nucleus of alveolar macrophages from neonatal mice. These data
      indicate that there is an early unresponsiveness of neonatal alveolar macrophages
      to Pneumocystis infection that is both intrinsic and related to the
      immunosuppressive environment found in neonatal lungs.

PMID- 22665379
TI  - Immune-activating properties of Panton-Valentine leukocidin improve the outcome
      in a model of methicillin-resistant Staphylococcus aureus pneumonia.
AB  - The Panton-Valentine leukocidin (PVL) is a cytotoxin expressed by many
      methicillin-resistant Staphylococcus aureus (MRSA) strains that cause community
      acquired infections (CA-MRSA). Its role in virulence however, is controversial,
      with clinical data suggesting that PVL-producing strains may cause less severe
      disease in humans. PVL is capable of lysing human white blood cells, but at
      sublytic amounts, PVL can activate protective host immunity in the absence of
      cell damage. The concentration-dependent reactions it elicits from host cells
      could be the reason for seemingly contradictory results about PVL's role in
      virulence. We hypothesized that a key to understanding PVL's action on host cells
      and, possibly, outcomes from infection is the amount of toxin present, a
      hypothesis previously supported in studies using a low-inoculum skin infection
      model, where low levels of PVL augmented innate immune resistance to infection.
      Here, we present additional data supporting this hypothesis using a mouse model
      of MRSA pneumonia, wherein we found increased virulence of isogenic Deltapvl
      strains and further confirmed PVL's capacity to activate proinflammatory
      responses from mouse and human neutrophils and pulmonary cells. Activation was
      measured as the production of phosphorylated p38 mitogen-activated protein kinase
      (MAPK) and proinflammatory cytokines interleukin-8 (IL-8) and KC (from human and
      mouse cells, respectively), as well as the release of antibacterial factors.
      Conversely, PVL lowered the levels of tumor necrosis factor alpha (TNF-alpha)
      produced in active pulmonary infection, while low doses induced apoptosis,
      suggesting that PVL also has the capacity to regulate inflammation. Our data
      indicate that, independent of its cytotoxic effects, PVL also plays an important
      and positive immunomodulatory role during MRSA infections.

PMID- 22665380
TI  - Contribution of urease to colonization by Shiga toxin-producing Escherichia coli.
AB  - Shiga toxin-producing Escherichia coli (STEC) is a food-borne pathogen with a low
      infectious dose that colonizes the colon in humans and can cause severe clinical
      manifestations such as hemolytic-uremic syndrome. The urease enzyme, encoded in
      the STEC chromosome, has been demonstrated to act as a virulence factor in other
      bacterial pathogens. The NH(3) produced as urease hydrolyzes urea can aid in
      buffering bacteria in acidic environments as well as provide an easily
      assimilated source of nitrogen that bacteria can use to gain a metabolic
      advantage over intact microflora. Here, we explore the role of urease in STEC
      pathogenicity. The STEC urease enzyme exhibited maximum activity near neutral pH
      and during the stationary-growth phase. Experiments altering growth conditions
      performed with three phylogenetically distinct urease-positive strains
      demonstrated that the STEC ure gene cluster is inducible by neither urea nor pH
      but does respond to nitrogen availability. Quantitative reverse transcription-PCR
      (qRT-PCR) data indicate that nitrogen inhibits the transcriptional response. The
      deletion of the ure gene locus was constructed in STEC strain 88-0643, and the
      ure mutant was used with the wild-type strain in competition experiments in mouse
      models to examine the contribution of urease. The wild-type strain was twice as
      likely to survive passage through the acidic stomach and demonstrated an enhanced
      ability to colonize the intestinal tract compared to the ure mutant strain. These
      in vivo experiments reveal that, although the benefit STEC gains from urease
      expression is modest and not absolutely required for colonization, urease can
      contribute to the pathogenicity of STEC.

PMID- 22665381
TI  - Impact of New York Heart Association classification, advanced age and patient
      prosthesis mismatch on outcomes in aortic valve replacement surgery.
AB  - OBJECTIVES More elderly patients (>80 years of age) are being referred for aortic
      valve replacement (AVR) with or without CABG. Current risk stratification models
      may not accurately predict the preoperative risk in these patients. We sought to
      determine which perioperative variables were relevant in determining short-term
      (30-day to in-hospital) outcomes in our intuition's series of consecutive AVR and
      AVR+CABG surgeries. We constructed a novel variable, patient-prosthesis mismatch
      (PPM) in the presence of diminished functional status (NYHA) classification, and
      studied its role as a predictor of mortality risk. METHODS From 2006 to 2010, 509
      patients undergoing AVR or AVR+CABG were evaluated. We created four groups based
      on the age and procedure (AVR >80, AVR+CABG >80, AVR <80 and AVR+CABG <80). PPM
      was defined as a calculated effective orifice area index value of <= 0.85, and it
      was calculated from manufacturer-generated charts. In-hospital and 30-day
      outcomes were assessed using the Chi-square and logistic regression analyses.
      RESULTS Overall observed 30-day mortality for all groups was lower (n = 8, 1.6%)
      than the STS-predicted mortality. Reoperation and PPM+NYHA class III-IV were
      associated with short-term mortality, but age >80 years was not. Octogenarians
      referred for surgery often had advanced heart failure. CONCLUSIONS Overall, short
      term outcomes after AVR with or without CABG were excellent and lower than
      predicted by the STS model. The low risk of AVR with CABG supports the
      consideration for earlier surgical referral and intervention for patients with a
      high likelihood of aortic stenosis progression before the onset of advanced heart
      failure ensues, regardless of the age. This should help further decrease the
      already very low mortality observed in these series. Efforts to avoid PPM in the
      setting of advanced heart failure may improve short-term results in this subset
      of patients.

PMID- 22665382
TI  - Custodiol versus blood cardioplegia in complex cardiac operations: an Australian
      experience.
AB  - OBJECTIVES: A single or dual-dose strategy for myocardial protection is
      attractive in long operations, in avoiding the need to interrupt the procedure to
      re-administer cardioplegia. We hypothesized that a single administration of
      Bretschneider histidine-tryptophan-ketoglutarate (HTK) crystalloid solution
      (Custodiol) offers myocardial protection comparable with repeated tepid blood
      cardioplegia. METHODS: We reviewed a prospectively compiled single-centre
      database containing all adult cardiac procedures performed from January 2005 to
      January 2011. Preoperative demographic and investigative data, operative
      variables and postoperative (30-day) mortality and morbidity were compared
      between the Custodiol and blood cardioplegia groups. The study primary endpoints
      were 30-day mortality, return to the operating theatre, myocardial infarction,
      stroke, postoperative requirement for an intra-aortic balloon pump, new renal
      failure, prolonged ventilation and re-admission to hospital within 30 days.
      Propensity score matching was performed to correct for any bias that may have
      been associated with the usage of Custodiol. RESULTS: A total of 1900 cardiac
      surgical procedures were identified of which 126 (7%) utilized Custodiol and 1774
      (93%) used blood cardioplegia as the primary cardioplegic agent. After propensity
      score matching, we were able to match 71 Custodiol cases one-to-one to those
      receiving blood cardioplegia. There were no statistically significant differences
      noted for any of the endpoints studied after propensity-score matching. In
      particular, the proportion of mortality (blood cardioplegia: 1 vs Custodiol 4%, P
      = 0.63) any mortality/morbidity (blood cardioplegia: 35 vs Custodiol: 39% P =
      0.46) was similar between the groups. CONCLUSIONS: The use of Custodiol is
      convenient, simple and at least as safe as tepid blood cardioplegia for
      myocardial protection in complex cardiac operations. A randomized prospective
      comparison of myocardial protection strategies is warranted.

PMID- 22665383
TI  - Prognostic significance of cancer within 1 mm of the circumferential resection
      margin in oesophageal cancer patients following neo-adjuvant chemotherapy.
AB  - OBJECTIVES: The prognostic significance of the circumferential resection margin
      (CRM) status in oesophageal cancer patients treated with neo-adjuvant
      chemotherapy and radical resection is controversial. Furthermore, it is currently
      unclear whether patients with cancer located at the CRM have a prognosis
      different from that of those with cancer within 1 mm of the CRM. This is the
      first study aiming to establish the optimal tumour-free distance from the CRM of
      an oesophagectomy in patients who have undergone neo-adjuvant chemotherapy.
      METHODS: The clinicopathological data of 232 oesophageal cancer patients from two
      UK centres were analysed. The CRM status was classified as Group A (cancer at the
      CRM), Group B (cancer within 1 mm but not at the CRM) and Group C (no cancer
      within 1 mm from the CRM). The relationship between the CRM status and patient
      survival was investigated. RESULTS: Thirty-eight specimens were classified as
      Group A, 89 as Group B and 105 as Group C. CRM status was related to the depth of
      tumour invasion (P < 0.001) and lymph node status (P < 0.001). The prognoses of
      the Group A and the Group B patients were similar. Both were poorer than that of
      the Group C patients (P = 0.008). Lymph node status was the only independent
      prognostic marker in multivariate analysis. CONCLUSIONS: Oesophageal cancer
      patients treated with preoperative chemotherapy with cancer cells at the CRM or
      within 1 mm of the CRM of the resected specimen have a significantly worse
      survival than patients with no cancer cells within 1 mm of the margin. However,
      this study suggests that the overall prognostic significance of the CRM status is
      limited in this cohort and the postoperative lymph node status is the most
      important prognostic factor in oesophageal cancer patients treated with neo
      adjuvant chemotherapy and surgery.

PMID- 22665384
TI  - First clinical results with the new sinus prosthesis used for valve-sparing
      aortic root replacement.
AB  - OBJECTIVES: Sinuses of Valsalva are important in assuring the physiological
      function of the aortic valve. This study evaluates short-term clinical results of
      the reimplantation technique for aortic valve-sparing root replacement using a
      new prosthesis with three separate sinuses of Valsalva (sinus prosthesis).
      METHODS: Between February 2009 and February 2011, a total of 23 patients (20 m/3
      f; mean age 52 +/- 14.8 years; range 24-70 years) with aortic root aneurysm
      underwent aortic valve-sparing procedures according to the David reimplantation
      technique using the new sinus prosthesis. Eighteen patients had tricuspid and
      five patients bicuspid aortic valves. All patients received clinical as well as
      echocardiographic examinations postoperatively (mean 13 +/- 9.3 months; 0.3-28
      months). RESULTS: There was no death and no reoperation of the aortic valve. At
      latest follow-up, most patients were in New York Heart Association class I (n =
      22; 95.7%). In 95.7% aortic valve regurgitation (AR) was 0 or 1+; one patient had
      AR 2+. Pressure gradients were between the normal range (mean pressure gradient
      4.7 +/- 1.9 mmHg). Echocardiographic images demonstrate physiological aortic root
      dimensions and configuration with three separate sinuses of Valsalva without
      systolic contact of leaflets to the wall. CONCLUSIONS: The new sinus prosthesis
      provides near normal root geometry and hemodynamics in valve-sparing aortic root
      replacement using the reimplantation technique, applicable for tricuspid and also
      bicuspid aortic valves.

PMID- 22665385
TI  - Traumatic leaflet injury during the use of percutaneous valves: a comparative
      study of balloon- and self-expandable valved stents.
AB  - OBJECTIVES: No comparison of balloon- or self-expandable valved stents (VSs)
      regarding tissue injury (if any) has been reported yet. The objective was to
      evaluate the occurrence and compare the severity of traumatic injury to leaflets
      from balloon- or self-expandable VSs. METHODS: Twelve homemade VSs were used for
      this experiment. These three-leaflet bovine pericardial bioprostheses had either
      a stainless steel (Group A) or a nitinol stent (Group B). After a 30-min period
      of compression (external diameter of VS reduced to 7 mm), the prostheses were
      deployed by balloon inflation (Group A) or by unsheathing (Group B). After H&E
      staining, pericardial leaflets were subsequently analyzed qualitatively and
      quantitatively for microscopic lesions. Non-crimped pericardial leaflets were
      used as a control group (Group C). RESULTS: All deployed VSs had microscopic
      lesions evocating traumatic injury to pericardial leaflets. Transverse fractures
      and longitudinal cleavages were the two main lesions encountered. Transverse
      fractures (no. per field) were significantly more frequent in the VS in
      comparison with the control group: 5 (range: 0-13), 4 (range: 0-9) and 0 (range:
      0-1) in Groups A, B and C, respectively (P < 0.001). Cleavages (no. per field)
      were also more frequent with balloon-expandable VSs compared with self-expandable
      VSs [3 (range: 0-7) vs 1(range: 0-8); P = 0.03]. CONCLUSIONS: Traumatic injury to
      the pericardial leaflets does occur during crimping and deployment of balloon- or
      self-expandable VSs. Injury may be more severe with the balloon-expandable VSs.
      The impact of such an injury on prosthesis durability requires a further
      investigation.

PMID- 22665386
TI  - Do Spaniards know their rights as patients?
AB  - BACKGROUND: In 2002, Spain introduced new legislation regulating the rights of
      patients. Spaniards have thus seen an increase in their capacity for decision
      making, bringing them into line with many other countries. However, the law
      changes do not mean to be acquainted with the new legislation and therefore,
      putting it into practice. OBJECTIVE: To analyse whether the rules governing
      patients' rights in Spain are sufficiently well known among patients and to
      identify the profile of those patients most aware of their rights. DESIGN: Cross
      sectional quota-sampled survey study. A total of 790 patients discharged from
      hospitals or attended in primary care took a telephone survey, 773 replayed.
      RESULTS: Twenty per cent had some knowledge of the rules governing patients'
      rights. Respondent characteristics that were associated with better knowledge of
      basic rights included: age of medical responsibility (P < 0.001), cases in which
      a doctor may inform family members (P < 0.001), whether or not a patient can
      refuse treatment (P < 0.001) and what is constituted by advance directives (P <
      0.001). Patients who opt for a more active role in consultations with medical
      professionals show greater knowledge of their rights (P < 0.01). Age was related
      to greater ignorance of these rights (P < 0.01). CONCLUSIONS: Patients' knowledge
      of their rights is quite limited, making it difficult for them to assert those
      rights in specific medical encounters. The youngest patients, the most demanding,
      and those who prefer to have the last word in decisions are those with the best
      knowledge of their rights as patients.

PMID- 22665387
TI  - HIVQUAL-T: monitoring and improving HIV clinical care in Thailand, 2002-08.
AB  - OBJECTIVE: We report experience of HIVQUAL-T implementation in Thailand. DESIGN:
      Program evaluation. SETTING: Twelve government hospital clinics. PARTICIPANTS:
      People living with HIV/AIDS (PLHAs) aged >=15 years with two or more visits to
      the hospitals during 2002-08. INTERVENTION: HIVQUAL-T is a process for HIV care
      performance measurement (PM) and quality improvement (QI). The program includes
      PM using a sample of eligible cases and establishment of a locally led QI
      infrastructure and process. PM indicators are based on Thai national HIV care
      guidelines. QI projects address needs identified through PM; regional workshops
      facilitate peer learning. Annual benchmarking with repeat measurement is used to
      monitor progress. MAIN OUTCOME MEASURE: Percentages of eligible cases receiving
      various HIV services. RESULTS: Across 12 participating hospitals, HIV care
      caseloads were 4855 in 2002 and 13 887 in 2008. On average, 10-15% of cases were
      included in the PM sample. Percentages of eligible cases receiving CD4 testing in
      2002 and 2008, respectively, were 24 and 99% (P< 0.001); for ARV treatment, 100
      and 90% (P= 0.74); for Pneumocystis jiroveci pneumonia prophylaxis, 94 and 93%
      (P= 0.95); for Papanicolau smear, 0 and 67% (P< 0.001); for syphilis screening, 0
      and 94% (P< 0.001); and for tuberculosis screening, 24 and 99% (P< 0.01). PM
      results contributed to local QI projects and national policy changes.
      CONCLUSIONS: Hospitals participating in HIVQUAL-T significantly increased their
      performance in several fundamental areas of HIV care linked to health outcomes
      for PLHA. This model of PM-QI has improved clinical care and implementation of
      HIV guidelines in hospital-based clinics in Thailand.

PMID- 22665388
TI  - Mecillinam/clavulanate combination: a possible option for the treatment of
      community-acquired uncomplicated urinary tract infections caused by extended
      spectrum beta-lactamase-producing Escherichia coli.
AB  - BACKGROUND: Extended-spectrum beta-lactamases (ESBLs) have emerged as an
      important mechanism of beta-lactam resistance among community uropathogens. We
      characterized the ESBLs of a collection of Escherichia coli isolates recovered
      from outpatients with urinary tract infection during nationwide surveillance
      conducted from 2005 to 2006 in Greece, and evaluated the in vitro activity of
      mecillinam and mecillinam/clavulanate against them. MATERIALS AND METHODS: ESBLs
      were characterized with PCR and sequencing. In vitro interactions were evaluated
      with agar dilution with and without clavulanate (4 mg/L) using an inoculum of
      10(4) or 10(6) cfu/spot as well as with time-kill methodology. RESULTS: Among 48
      ESBL producers, 47 (97.9%) were susceptible to mecillinam. CTX-M-type enzymes
      were produced by 87.2%, with CTX-M-3 being the most prevalent. SHV enzymes were
      found in 10.6%, VEB enzymes in 2.1%, TEM enzymes in 19.2% and OXA-type enzymes in
      12.8%. Synergy with clavulanate was detected in 60.4% using the agar dilution
      method and in 43.8% using the time-kill methodology. An inoculum effect was
      detected in 64.6% of isolates, but this phenomenon was inverted and synergy was
      evidenced for 85.4% with clavulanate. When a high inoculum was used, 60.4%
      (29/48) were resistant to mecillinam, but 97.9% (47/48) were susceptible in the
      presence of clavulanate. CONCLUSIONS: CTX-M-type enzymes were the most prevalent
      among ESBL-producing E. coli uropathogens in Greece. Mecillinam may be useful in
      uncomplicated cystitis caused by ESBL producers with low MICs. The addition of
      the inhibitor could improve and extend the activity of mecillinam, even in the
      setting of infection with a high bacterial inoculum, and merits clinical
      evaluation.

PMID- 22665389
TI  - Release of gliotransmitters through astroglial connexin 43 hemichannels is
      necessary for fear memory consolidation in the basolateral amygdala.
AB  - Recent in vitro evidence indicates that astrocytes can modulate synaptic
      plasticity by releasing neuroactive substances (gliotransmitters). However,
      whether gliotransmitter release from astrocytes is necessary for higher brain
      function in vivo, particularly for memory, as well as the contribution of
      connexin (Cx) hemichannels to gliotransmitter release, remain elusive. Here, we
      microinfused into the rat basolateral amygdala (BLA) TAT-Cx43L2, a peptide that
      selectively inhibits Cx43-hemichannel opening while maintaining synaptic
      transmission or interastrocyte gap junctional communication. In vivo blockade of
      Cx43 hemichannels during memory consolidation induced amnesia for auditory fear
      conditioning, as assessed 24 h after training, without affecting short-term
      memory, locomotion, or shock reactivity. The amnesic effect was transitory,
      specific for memory consolidation, and was confirmed after microinfusion of
      Gap27, another Cx43-hemichannel blocker. Learning capacity was recovered after
      coinfusion of TAT-Cx43L2 and a mixture of putative gliotransmitters (glutamate,
      glutamine, lactate, d-serine, glycine, and ATP). We propose that gliotransmitter
      release from astrocytes through Cx43 hemichannels is necessary for fear memory
      consolidation at the BLA. Thus, the present study is the first to demonstrate a
      physiological role for astroglial Cx43 hemichannels in brain function, making
      these channels a novel pharmacological target for the treatment of psychiatric
      disorders, including post-traumatic stress disorder.

PMID- 22665390
TI  - Single-Incision Sigmoid Resection: Shouldn't the Incision Be Just a Little Bit
      Longer?

PMID- 22665391
TI  - Pattern clustering with statistical methods using a DNA-based algorithm.
AB  - Clustering is commonly exploited in engineering, management, and science fields
      with the objective of revealing structure in pattern data sets. In this article,
      through clustering we construct meaningful collections of information granules
      (clusters). Although the underlying goal is obvious, its realization is fully
      challenging. Given their nature, clustering is a well-known NP-complete problem.
      The existing algorithms commonly produce some suboptimal solutions. As a vehicle
      of pattern clustering, we discuss in this article how to use a DNA-based
      algorithm. We also discuss the details of encoding being used here with
      statistical methods combined with the DNA-based algorithm for pattern clustering.

PMID- 22665392
TI  - Classification of multicolor fluorescence in situ hybridization (M-FISH) images
      with sparse representation.
AB  - There has been a considerable interest in sparse representation and compressive
      sensing in applied mathematics and signal processing in recent years but with
      limited success to medical image processing. In this paper we developed a sparse
      representation-based classification (SRC) algorithm based on L1-norm minimization
      for classifying chromosomes from multicolor fluorescence in situ hybridization (M
      FISH) images. The algorithm has been tested on a comprehensive M-FISH database
      that we established, demonstrating improved performance in classification. When
      compared with other pixel-wise M-FISH image classifiers such as fuzzy c-means
      (FCM) clustering algorithms and adaptive fuzzy c-means (AFCM) clustering
      algorithms that we proposed earlier the current method gave the lowest
      classification error. In order to evaluate the performance of different SRC for M
      FISH imaging analysis, three different sparse representation methods, namely,
      Homotopy method, Orthogonal Matching Pursuit (OMP), and Least Angle Regression
      (LARS), were tested and compared. Results from our statistical analysis have
      shown that Homotopy based method is significantly better than the other two
      methods. Our work indicates that sparse representations based classifiers with
      proper models can outperform many existing classifiers for M-FISH classification
      including those that we proposed before, which can significantly improve the
      multicolor imaging system for chromosome analysis in cancer and genetic disease
      diagnosis.

PMID- 22665393
TI  - Molecular communication and networking: opportunities and challenges.
AB  - The ability of engineered biological nanomachines to communicate with biological
      systems at the molecular level is anticipated to enable future applications such
      as monitoring the condition of a human body, regenerating biological tissues and
      organs, and interfacing artificial devices with neural systems. From the
      viewpoint of communication theory and engineering, molecular communication is
      proposed as a new paradigm for engineered biological nanomachines to communicate
      with the natural biological nanomachines which form a biological system. Distinct
      from the current telecommunication paradigm, molecular communication uses
      molecules as the carriers of information; sender biological nanomachines encode
      information on molecules and release the molecules in the environment, the
      molecules then propagate in the environment to receiver biological nanomachines,
      and the receiver biological nanomachines biochemically react with the molecules
      to decode information. Current molecular communication research is limited to
      small-scale networks of several biological nanomachines. Key challenges to bridge
      the gap between current research and practical applications include developing
      robust and scalable techniques to create a functional network from a large number
      of biological nanomachines. Developing networking mechanisms and communication
      protocols is anticipated to introduce new avenues into integrating engineered and
      natural biological nanomachines into a single networked system. In this paper, we
      present the state-of-the-art in the area of molecular communication by discussing
      its architecture, features, applications, design, engineering, and physical
      modeling. We then discuss challenges and opportunities in developing networking
      mechanisms and communication protocols to create a network from a large number of
      bio-nanomachines for future applications.

PMID- 22665394
TI  - Conjugation of active iron superoxide dismutase to nanopatterned surfaces.
AB  - Superoxide dismutase enzymes (SODs) are an essential part of the first line of
      cellular defense system against free radicals species. They catalyze the
      dismutation of superoxide radicals into oxygen and hydrogen peroxide. Although
      several studies have examined the attachment of superoxide dismutases to
      nanoparticles and nanostructures, never has been used a member of the Fe/MnSOD
      family. In this study, the behavior of plant origin FeSOD enzyme on three
      different nanopatterned surfaces was investigated as a function of covalent and
      electrostatic binding. Fluorescence microscopy was used to demonstrate that the
      protein is attached only to the gold layer. We also examined the activity of SOD
      by a colorimetric assay, and we have shown that the enzyme remains active after
      attachment to the three different surfaces under both kind of binding
      (electrostatic and covalent). This methodology could be useful for those who want
      to functionalize nanostructures with a SOD enzyme and test the activity. This
      process could be of great interest for the development of peroxynitrite and
      superoxide biosensors.

PMID- 22665395
TI  - Comparative analysis of Rac1 binding efficiency with different classes of
      ligands: morpholines, flavonoids and imidazoles.
AB  - The focal adhesion pathway has a great impact on cellular growth and survival.
      Its disregulation is correlated with the loss of cellular mechanical properties.
      Such modifications are, in many cases, associated with pathologies such as cancer
      and cardiovascular diseases. Actin remodeling is a critical reaction cascade
      embedded in focal adhesion pathway, and Rac1 is one of the proteins involved in
      actin remodeling. In order to design highly selective pharmacophores against this
      target, it is necessary to maximize the binding affinity of chemical entities
      against Rac1. To this purpose we propose an integrative chemo-bioinformatics tool
      to screen ligand specificity for a target protein. Our integrative workflow
      includes chemo-informatics data mining (Chemical System), structural
      bioinformatics and combined exploratory data analysis. We have applied this
      integrative chemo-bioinformatics workflow to a comparative analysis of three
      different classes of ligands (morpholines, flavonoids and imidazoles) against the
      Rac1 protein. Our analysis emphasizes the presence of several ligands that
      preferentially dock Rac1 in the domain that seems to be responsible for Rac1
      phospholipase C gamma 1 interaction. Recent studies have highlighted the Rac1 and
      PLC interactions in platelet adhesion. Our study has highlighted the role of Rac1
      PLC gamma1 interaction in cytoskeleton remodeling associated with cardiovascular
      diseases. Rac1 PLC interaction is Calcium dependent. This suggest that some of
      the analysed ligands, could be used to control the Calcium dependent cytoskeleton
      remodeling since they dock Rac1 in the switch 2 domain. Our results, in a
      nanotechnology perspective, also endorse the use Rac1's switch 2 domain suitable
      for new highly specific biosensors.

PMID- 22665396
TI  - Significance of exercise induced U wave inversion as a marker for coronary artery
      disease.
AB  - Exercise stress testing for detecting inducible ischaemia was first introduced in
      the 1950s and remained one of the only methods of stressing the heart for years
      to come. The presence of inducible ischaemia was assessed by ECG changes during
      exercise apart from other factors, namely, duration of exercise, blood pressure
      and heart rate response, metabolic equivalents achieved, etc. With the emergence
      of other tests to look for inducible ischaemia, for example, dobutamine stress
      echocardiography and myocardial perfusion scanning and also as the threshold for
      invasive evaluation has decreased, unusual and infrequently encountered ECG
      changes are not looked for during exercise stressing with the same degree of
      diligence. The authors describe below the case of a 49-year-old male whose left
      anterior descending artery stenosis was diagnosed on exercise stress test on the
      basis of a negative U wave.

PMID- 22665397
TI  - Improvement in refractory heart failure by nephrectomy for renal tumour.
AB  - Hypoalbuminaemia and anaemia are conditions known to aggravate congestive cardiac
      failure (CCF). Renal cell carcinoma is often associated with hypoalbuminaemia and
      anaemia. The authors report an interesting case of a patient with severe
      refractory CCF who incidentally was found to have a massive renal cell tumour.
      Clinically, his heart failure was being aggravated by hypoalbuminaemia and
      anaemia. Despite aggressive diuretic therapy and multiple blood and albumin
      transfusions, there was no clinical improvement. He subsequently underwent
      nephrectomy of the renal tumour, with subsequent dramatic clinical improvement in
      his heart failure. His symptoms resolved completely and he did not require any
      further diuretic therapy.

PMID- 22665398
TI  - A neonatal case of congenital coronary artery fistula.
AB  - Coronary artery fistulae (CAF) are rare forms of congenital heart disease with an
      incidence of one in 50 000 live births. The authors present the case of an
      asymptomatic neonate with a precordial murmur. Pre and postductal saturations,
      blood pressure and ECG were normal. Echocardiography revealed a large right
      coronary artery fistula to the right ventricle (4.5 mm). At 11 months,
      transcatheter occlusion of the fistula with a vascular plug was performed. A year
      on, the child was thriving, ECG and echocardiogram remained normal. CAF
      complications and symptoms (including aneurysm, myocardial ischaemia, angina,
      heart failure and dyspnoea) are commoner in older patients, so traditionally we
      intervene early. With increasing case reports of spontaneous closure of even
      large and symptomatic fistulae, management of especially asymptomatic children is
      unclear. Long-term complications of intervention also remain largely unknown. As
      such more information is required on the conditions natural history to better
      manage patients and counsel parents.

PMID- 22665399
TI  - An unusual case of rectal perforation resulting in extensive surgical emphysema.

PMID- 22665400
TI  - Skull base oncocytoma presenting as epistaxis: an unusual presentation of a rare
      tumour successfully managed with active surveillance.
AB  - Oncocytomas are rare tumours, usually occurring in the salivary glands, but may
      very occasionally occur in other sites. The authors present a skull base
      oncocytoma as a rare cause of spontaneous epistaxis. Following diagnosis through
      imaging and intranasal biopsy, the patient opted for annual surveillance instead
      of active treatment and made a full recovery nonetheless. Skull base oncocytoma
      is a rare tumour that may result in otherwise common symptomatology. While
      excision is the mainstay of management, active surveillance may be a viable
      alternative for select patients.

PMID- 22665401
TI  - Irreversible airway obstruction due to innominate artery compression of the
      trachea.

PMID- 22665402
TI  - Large bowel obstruction due to impaction of a gallstone.
AB  - Gallstone ileus is a complication of cholelithiasis resulting from a fistula
      between the gallbladder and the gastrointestinal tract. If sufficiently large, a
      gallstone may lodge at the narrowest part of the gastrointestinal tract, usually
      the terminal ileum, and present with small bowel obstruction. Here the authors
      present the unusual case of an 82-year-old man who developed symptoms and signs
      of large bowel obstruction due to an untreated gallstone, measuring 7*4.5 cm,
      that fistulated into the transvere colon and subsequently impacted in the sigmoid
      colon. An emergency laparotomy with sigmoid colotomy was undertaken to remove the
      obstructing gallstone, and the patient made a full recovery.

PMID- 22665403
TI  - 46 XY gonadal dysgenesis in adulthood 'pitfalls of late diagnosis'.
AB  - Disorders of sex development (DSD) include congenital conditions where
      developments of chromosomal, gonadal or anatomical sex are atypical. Ostrer in
      2000, reported a prevalence of 1:20 000 for 46 XY DSD and complete gonadal
      dysgenesis. A 21-year-old patient consulted for sexual ambiguity at the out
      patient department of the Philippine general hospital. At birth, the perceived
      female external genitalia and clitoromegaly, led the parents to register and
      eventually rear the patient as a female. At puberty, he developed masculine
      features and growth of phallus. Patient was more interested in male activities
      and began to identify himself as male in the community. The discrepancy between
      his birth certificate and his male gender jeopardised his ambition to become a
      policeman; this led him to seek medical consult. On physical examination, he was
      phenotypically male. The external genitalia showed the phallus length of 3.5 cm
      and perineoscrotal hypospadias. Chromosomal sex was normal 46 XY with neither
      numerical nor structural aberrations in all cell lines, serum testosterone was
      low and gonadotrophins were elevated. Whole abdominal CT scan showed bilaterally
      undescended testes and a 4.5 cm blind vaginal pouch seen on genitogram. Bilateral
      orchidectomy with first stage repair of hypospadias was performed. On
      histopathology, the right testis was fibrotic and the left testis showed minimal
      testicular tissue with absent spermatids. The clinical, endocrine, cytogenetic
      and histopathologic data are consistent with gonadal dysgenesis syndrome.

PMID- 22665404
TI  - 'Where am I?'--An unusual stroke presentation.

PMID- 22665405
TI  - Preeclampsia and retinopathy of prematurity in preterm births.
AB  - OBJECTIVE: The relationship between gestational hypertension, preeclampsia, and
      the risk of retinopathy of prematurity (ROP) remains unclear. Thus, we used a
      large cohort database to study the influence of maternal gestational hypertension
      and preeclampsia on the occurrence of ROP in preterm infants. METHODS: We used
      data from a previous retrospective cohort study that includes 25,473 eligible
      preterm neonates. We examined the association between gestational hypertension,
      preeclampsia, and ROP while controlling for potential confounders by multiple
      logistic regression analysis. RESULTS: Of the 8758 early preterm infants
      (gestational age <34 weeks), 1024 (11.69%) had ROP, while of the 16,715 late
      preterm infants, only 29 (0.17%) had ROP. After adjusting for confounders,
      preeclampsia was associated with a significantly reduced risk of ROP (adjusted
      odds ratio [aOR], 0.65; 95% confidence interval [CI], 0.49-0.86 for early preterm
      birth; aOR, 0.10; 95% CI, 0.01-0.93 for late preterm birth; aOR, 0.66; 95% CI,
      0.50-0.87 for all preterm births). Gestational hypertension was not significantly
      associated with ROP at early or late preterm births. CONCLUSIONS: Preeclampsia,
      but not gestational hypertension, was associated with a reduced risk of ROP in
      preterm births.

PMID- 22665406
TI  - Baby-Friendly hospital practices and meeting exclusive breastfeeding intention.
AB  - OBJECTIVE: To describe mothers' exclusive breastfeeding intentions and whether
      Baby-Friendly hospital practices are associated with achieving these intentions.
      METHODS: In the 2005-2007 Infant Feeding Practices Study II, women completed a
      prenatal questionnaire and approximately monthly questionnaires through 12
      months. Mothers met their prenatal exclusive breastfeeding intention if their
      duration after the hospital stay (excluding hospital supplementation) equaled or
      exceeded their intention. Primary predictor variables included 6 Baby-Friendly
      hospital practices: breastfeeding within 1 hour of birth, giving only breast
      milk, rooming in, breastfeeding on demand, no pacifiers, and information on
      breastfeeding support. RESULTS: Among women who prenatally intended to
      exclusively breastfeed (n = 1457), more than 85% intended to do so for 3 months
      or more; however, only 32.4% of mothers achieved their intended exclusive
      breastfeeding duration. Mothers who were married and multiparous were more likely
      to achieve their exclusive breastfeeding intention, whereas mothers who were
      obese, smoked, or had longer intended exclusive breastfeeding duration were less
      likely to meet their intention. Beginning breastfeeding within 1 hour of birth
      and not being given supplemental feedings or pacifiers were associated with
      achieving exclusive breastfeeding intention. After adjustment for all other
      hospital practices, only not receiving supplemental feedings remained significant
      (adjusted odds ratio = 2.3, 95% confidence interval = 1.8, 3.1). CONCLUSIONS: Two
      thirds of mothers who intend to exclusively breastfeed are not meeting their
      intended duration. Increased Baby-Friendly hospital practices, particularly
      giving only breast milk in the hospital, may help more mothers achieve their
      exclusive breastfeeding intentions.

PMID- 22665407
TI  - Screening, brief intervention, and referral for alcohol use in adolescents: a
      systematic review.
AB  - BACKGROUND AND OBJECTIVE: Alcohol use by adolescents is widespread and is
      connected to a number of negative health and social outcomes. Adolescents
      receiving emergent care for injuries are often linked with risky use of alcohol.
      The trauma system has widely adopted the use of screening, brief intervention,
      and referral to treatment (SBIRT) for preventing alcohol-related injury
      recidivism and other negative outcomes. The purpose of this article is to review
      the evidence around SBIRT with adolescent patients in acute care settings.
      METHODS: This article reviews 7 randomized controlled trials evaluating risky
      drinking interventions among adolescent patients in acute care settings. All
      studies took place in the emergency departments of level I trauma centers.
      RESULTS: Four of the 7 studies reviewed demonstrated a significant intervention
      effect; however, no one intervention reduced both alcohol consumption and alcohol
      related consequences. Two of these 4 studies only included patients ages 18 and
      older. Subgroup analyses with adolescents engaged in risky alcohol-related
      behaviors, conducted in 2 of the studies, showed significant intervention
      effects. Five studies showed positive consumption and/or consequences for all
      study participants regardless of condition, suggesting that an emergent injury
      and/or the screening process may have a protective effect. CONCLUSIONS: Based on
      existing evidence, it is not clear whether SBIRT is an effective approach to
      risky alcohol use among adolescent patients in acute care. Additional research is
      needed around interventions and implementation.

PMID- 22665408
TI  - Genetics of pediatric obesity.
AB  - Onset of obesity has been anticipated at earlier ages, and prevalence has
      dramatically increased worldwide over the past decades. Epidemic obesity is
      mainly attributable to modern lifestyle, but family studies prove the significant
      role of genes in the individual's predisposition to obesity. Advances in
      genotyping technologies have raised great hope and expectations that genetic
      testing will pave the way to personalized medicine and that complex traits such
      as obesity will be prevented even before birth. In the presence of the pressing
      offer of direct-to-consumer genetic testing services from private companies to
      estimate the individual's risk for complex phenotypes including obesity, the
      present review offers pediatricians an update of the state of the art on genomics
      obesity in childhood. Discrepancies with respect to genomics of adult obesity are
      discussed. After an appraisal of findings from genome-wide association studies in
      pediatric populations, the rare variant-common disease hypothesis, the
      theoretical soil for next-generation sequencing techniques, is discussed as
      opposite to the common disease-common variant hypothesis. Next-generation
      sequencing techniques are expected to fill the gap of "missing heritability" of
      obesity, identifying rare variants associated with the trait and clarifying the
      role of epigenetics in its heritability. Pediatric obesity emerges as a complex
      phenotype, modulated by unique gene-environment interactions that occur in
      periods of life and are "permissive" for the programming of adult obesity. With
      the advent of next-generation sequencing techniques and advances in the field of
      exposomics, sensitive and specific tools to predict the obesity risk as early as
      possible are the challenge for the next decade.

PMID- 22665409
TI  - Hyponatremia-associated rhabdomyolysis following exercise in an adolescent with
      cystic fibrosis.
AB  - Adolescents with well-controlled cystic fibrosis, including good lung function
      and appropriate growth, commonly participate in competitive athletic activities.
      We present the case of an adolescent male with cystic fibrosis, hyponatremia,
      dehydration, and rhabdomyolysis after participating in football practice on a
      summer morning. The patient presented with severe myalgia and serum sodium of 129
      mmol/L, chloride 90 mmol/L, and creatine phosphokinase 1146 U/L. Aggressive
      hydration with intravenous 0.9% saline resulted in clinical improvement with no
      renal or muscular sequelae. Health care providers need to educate patients with
      cystic fibrosis about maintaining adequate hydration and sodium repletion during
      exercise. Research is needed regarding the appropriate amount and composition of
      oral rehydration fluids in exercising individuals with cystic fibrosis, as the
      physiology encountered in these patients provides a unique challenge to
      maintaining electrolyte balance and stimulation of thirst.

PMID- 22665410
TI  - Interfacility transfers of noncritically ill children to academic pediatric
      emergency departments.
AB  - OBJECTIVES: We aimed to characterize the demographics, diagnoses, and management
      of transferred patients who were directly discharged from the emergency
      department (ED) or admitted less than 24 hours. METHODS: We conducted a
      retrospective, cross-sectional study of patients classified as interfacility ED
      transfers over a 12-month period in the Pediatric Health Information System
      database, an administrative database of 42 tertiary care pediatric US hospitals.
      The primary study outcomes were ED resource utilization at the receiving facility
      with a focus on children who were discharged directly from the ED or admitted
      less than 24 hours. RESULTS: Overall, 24,905 interfacility transfers were
      identified, accounting for 1.3% of the ED volume of these academic pediatric
      centers. Of these, 24.7% were discharged directly from the ED and 17.0% were
      admitted for less than 24 hours. Among those directly discharged from the ED, the
      3 most common complaints were orthopedic problems, nonsurgical abdominal pain,
      and viral gastroenteritis; 20.7% received no medical or procedural intervention.
      Among those admitted for less than 24 hours, the 3 most common complaints were
      orthopedic problems, traumatic head injury, and gastrointestinal conditions.
      CONCLUSIONS: A significant proportion of interfacility transfers to academic
      pediatric EDs is discharged directly from the ED or is admitted for less than a
      day. These patients and their clinical outcomes provide insight into the
      educational needs and medical capabilities of referring hospitals and clinicians.

PMID- 22665411
TI  - Obesity counseling by pediatric health professionals: an assessment using
      nationally representative data.
AB  - OBJECTIVE: Examine the rate of screening for adolescent overweight and obesity by
      pediatric health care professionals and the provision of advice on healthy eating
      and physical activity. METHODS: Our sample contains adolescents 11 to 17 years
      old (6911 girls and 6970 boys) from the 2001-2007 Medical Expenditure Panel
      Survey who reported having at least 1 health provider visit in the previous 12
      months. Using logistic regression, we investigated factors associated with
      whether parents reported that their children were weighed and measured and
      whether they or their children received counseling on their eating habits and
      physical activity. All models were estimated separately by gender. RESULTS: Forty
      seven percent of girls and 44% of boys who visited a health provider were advised
      to eat healthy, and 36% of boys and girls were advised to exercise more. Obese
      boys and girls were both more likely to be advised to eat healthy (odds ratio
      [OR] = 2.10, P < .001 and OR = 1.70, P < .001) and exercise more (OR = 2.37, P <
      .001 and OR = 1.90, P < .001) than adolescents who have normal weight. However,
      overweight boys and girls were counseled at a much lower rate than those who were
      obese. Adolescents who were more likely to receive such advice lived in the
      northeast, were from higher-income households, had parents with at least some
      college education, and had a usual source of medical care. CONCLUSIONS: Greater
      efforts should be made to incorporate guidelines on childhood obesity screening
      and counseling into clinical practice.

PMID- 22665413
TI  - Dynamic evolution of practice guidelines: analysis of deviations from assessment
      and management plans.
AB  - OBJECTIVE: A Standardized Clinical Assessment and Management Plan (SCAMP)
      standardizes the care of patients with a predefined diagnosis while actively
      inviting and collecting data on clinician deviations (DEVs) from its
      recommendations. For 3 different pediatric cardiac diagnoses managed by SCAMPs,
      we determined the frequency of, types of, and reasons for DEVs, which are
      considered to be a valuable source of information and innovation. METHODS: DEVs
      were collected as part of SCAMP implementation. DEVs were reviewed by the SCAMP
      committee chairperson and by a separate protocol deviation committee; they were
      characterized as either justifiable (J), possibly justifiable (PJ), or not
      justifiable (NJ). RESULTS: We analyzed 415 patients, 484 clinic encounters, and
      216 DEVs. Eighty-six (39.8%) of the DEVs were J, 21 (9.7%) were PJ, and 109
      (50.4%) were NJ. The percentage of NJ DEVs relative to the number of
      opportunities for DEV was 4.1%. J and PJ DEVs were mostly due to management of
      unrelated conditions (11% overall) or special circumstances (22% overall). NJ
      DEVs primarily involved follow-up intervals (66%) and deleted tests (24%). The
      reason for deviating from SCAMP recommendations was not given for 31% of DEVs,
      even though such information was requested. CONCLUSIONS: The overall low rate of
      NJ DEV suggests that practitioners generally accept SCAMP recommendations, but
      improved capture of practitioners' reasons for deviating from those
      recommendations is needed. This analysis revealed multiple opportunities for
      improving patient care, suggesting that this process can be useful in both
      promulgating sound practice and evolving improved approaches to patient
      management.

PMID- 22665412
TI  - Self-reported adolescent health status of extremely low birth weight children
      born 1992-1995.
AB  - OBJECTIVES: To compare the self-reported health of extremely low birth weight
      (ELBW, <1 kg) adolescents with that of normal birth weight (NBW) controls and the
      children's assessments of their general health at ages 8 versus 14 years.
      METHODS: One hundred sixty-eight ELBW children and 115 NBW controls of similar
      gender and sociodemographic status completed the Child Health and Illness Profile
      Adolescent Edition at age 14 years. It includes 6 domains: Satisfaction, Comfort,
      Resilience, Risk Avoidance, Achievement, and Disorders. At age 8 years, the
      children had completed the Child Health and Illness Profile-Child Edition.
      Results were compared between ELBW and NBW subjects adjusting for gender and
      sociodemographic status. RESULTS: ELBW adolescents rated their health similar to
      that of NBW adolescents in the domains of Satisfaction, Comfort, Resilience,
      Achievement and Disorders but reported more Risk Avoidance (effect size [ES] 0.6,
      P < .001). In the subdomain of Resilience, they also noted less physical activity
      (ES -0.58, P < .001), and in the subdomain of Disorders, more long-term surgical
      (ES -0.49) and psychosocial disorders (ES -0.49; both P < .01). Both ELBW and NBW
      children reported a decrease in general health between ages 8 and 14 years, which
      did not differ significantly between groups. CONCLUSIONS: ELBW adolescents report
      similar health and well-being compared with NBW controls but greater risk
      avoidance. Both ELBW and NBW children rate their general health to be poorer at
      age 14 than at age 8 years, possibly due to age-related developmental changes.

PMID- 22665414
TI  - Pediatric residents' perspectives on reducing work hours and lengthening
      residency: a national survey.
AB  - OBJECTIVE: In 2011, the Accreditation Council on Graduate Medical Education
      increased restrictions on resident duty-hours. Additional changes have been
      considered, including greater work-hours restrictions and lengthening residency.
      Program directors tend to oppose further restrictions; however, residents' views
      are unclear. We sought to determine whether residents support these proposals,
      and if so why. METHODS: We surveyed US pediatric residents from a probability
      sample of 58 residency programs. We used multivariate logistic regression to
      determine predictors of support for (1) a 56-hour workweek and (2) the addition
      of 1 year to residency to achieve a 56-hour week. RESULTS: Fifty-seven percent of
      sampled residents participated (n = 1469). Forty-one percent of respondents
      supported a 56-hour week, with 28% neutral and 31% opposed. Twenty-three percent
      of all residents would be willing to lengthen training to reduce hours. The
      primary predictors of support for a 56-hour week were beliefs that it would
      improve education (odds ratio [OR] 8.6, P < .001) and quality of life (OR 8.7, P
      < .001); those who believed patient care would suffer were less likely to support
      it (OR 0.10, P < .001). Believing in benefits to education without decrement to
      patient care also predicted support for a 56-hour-week/4-year program.
      CONCLUSIONS: Pediatric residents who support further reductions in work-hours
      believe reductions have positive effects on patient care, education, and quality
      of life. Most would not lengthen training to reduce hours, but a minority prefers
      this schedule. If evidence mounts showing that reducing work-hours benefits
      education and patient care, pediatric residents' support for the additional year
      may grow.

PMID- 22665415
TI  - The use of patient pictures and verification screens to reduce computerized
      provider order entry errors.
AB  - OBJECTIVE: To determine whether an order verification screen, including a patient
      photograph, is an effective strategy for reducing the risk that providers will
      place orders in an unintended patient's electronic medical record (EMR). METHODS:
      We describe several changes to the EMR/provider interface and ordering workflow
      that were implemented as one part of a hospital-wide quality improvement effort
      to improve patient identification and verification practices. We measured the
      impact by comparing the number of reported incidents of care being provided to
      any patient other than for whom it was intended before the intervention, and
      directly after the intervention. RESULTS: For the year before the interventions
      described herein, placement of orders in the incorrect patient's chart was the
      second most common cause of care being provided to the wrong patient, comprising
      24% of the reported errors. In the 15 months after the implementation of an order
      verification screen with the patient's photo centrally placed on the screen, no
      patient whose picture was in the EMR was reported to have received unintended
      care based on erroneous order placement in his or her chart. CONCLUSIONS: The
      incorporation of patient pictures within a computerized order entry verification
      process is an effective strategy for reducing the risk that erroneous placement
      of orders in a patient's EMR will result in unintended care being provided to an
      incorrect patient.

PMID- 22665416
TI  - Secular trends in BMI and blood pressure among children and adolescents: the
      Bogalusa Heart Study.
AB  - OBJECTIVE: The prevalence of obesity among children and adolescents increased by
      almost threefold from the 1970s to 2000. We examined whether these secular
      changes in BMI were accompanied by increases in blood pressure levels. METHODS: A
      total of 24,092 examinations were conducted among 11,478 children and adolescents
      (aged 5-17 years) from 1974 to 1993 in the Bogalusa Heart Study (Louisiana).
      RESULTS: The prevalence of obesity increased from 6% to 17% during this period.
      In contrast, only small changes were observed in levels of systolic blood
      pressure (SBP) and diastolic blood pressure (DBP), and neither mean nor high
      (based on the 90th percentile from the Fourth Report on the Diagnosis,
      Evaluation, and Treatment of High Blood Pressure in Children and Adolescents)
      levels increased over the 20-year period. Within each race-gender group, mean
      levels of SBP did not change, whereas mean levels of DBP decreased by 2 mm Hg (P
      < .001 for trend). Levels of BMI were positively associated with levels of SBP
      and DBP within each of the 7 examinations, and controlling for BMI (along with
      other covariates) indicated that only ~60% as many children as expected had high
      levels of blood pressure in 1993. CONCLUSIONS: Our finding that levels of DBP and
      SBP among children in this large sample did not increase despite the increases
      that were seen in obesity indicates that changes in blood pressure levels in a
      population do not necessarily parallel changes in obesity. Additional study of
      the potential characteristics that have ameliorated the expected increase in high
      blood pressure could lead to further reductions in risk.

PMID- 22665417
TI  - Abnormalities of vascular structure and function in children with Perthes
      disease.
AB  - BACKGROUND AND OBJECTIVES: Perthes disease is a childhood precipitant to
      osteoarthritis of the hip, for which the etiology and mechanism are unknown.
      There is mounting evidence to suggest a vascular insult is responsible for
      disease, and it is suggested that this may have long-term implications for the
      vascular health of affected individuals. This study sought to use ultrasound
      measures to investigate vascular structure and function in children affected by
      Perthes disease. METHODS: This case control study encompassed 149 cases and 146
      controls, frequency matched for age and gender. Endothelial function was measured
      by using the technique of flow-mediated dilation of the brachial artery, and
      alterations in arterial flow were recorded in response to an ischemic stimulus.
      RESULTS: There was a significant structural alteration in the vasculature among
      individuals with Perthes disease (resting brachial artery diameter (cases 2.97 mm
      versus controls 3.11 mm; P = .01), which remained even after adjusting for
      height. In addition, there was a notable reduction in blood velocity (cases 33.84
      cm/s versus controls 37.83 cm/s; P = .01) and blood flow (cases 149.82 mL/min
      versus controls 184.67 mL/min; P = .001), which was independent of baseline
      arterial size. There was no evidence to suggest that flow-mediated dilation of
      the brachial artery was impaired among affected individuals (P = .71).
      CONCLUSIONS: Children with Perthes disease exhibit small artery caliber and
      reduced function, which is independent of body composition. These data imply that
      that Perthes disease may reflect a wider vascular phenomenon that could have long
      term implications for the vascular health of affected individuals.

PMID- 22665418
TI  - State of dental care among Medicaid-enrolled children in the United States.
AB  - OBJECTIVE: To evaluate the prevalence of dental care visits (DCV) in 2007 in the
      United States among Medicaid-enrolled children from birth to age 18 and measure
      progress since 2002. METHODS: By using Medicaid research files and information
      from the Centers for Medicare & Medicaid Services 416 Early Periodic Screening,
      Diagnostic, and Treatment forms, we calculated the prevalence of DCV in 50 states
      and the District of Columbia, stratifying by age, race, type of health plan, and
      Children's Health Insurance Program status. RESULTS: The prevalence of having DCV
      ranged from 12% depending on age, to 49% with a median value of 33% but did not
      exceed 50% in any state. The median percent change between 2002 and 2007 was 16%.
      DCV among toddlers and infants were low in all but 3 states and in most states
      peaked at age of school entry to >60% in some states. In most states, there were
      few racial differences in the prevalence of DCV. Children enrolled in Primary
      Care Case Management tended to have the highest DCV, the effect of Children's
      Health Insurance Program enrollment on the number of DCV was generally positive.
      CONCLUSIONS: To our knowledge, this is the first study to evaluate the prevalence
      of dental care by using paid Medicaid claims. Consistent with other reports, 
      levels of DCV were low; but  when the number of DCV was stratified by age and
      type plan, striking patterns emerged suggesting that a combination of school
      programs and having a medical home may have a positive impact on dental care.

PMID- 22665419
TI  - The history of the discovery of blood circulation: unrecognized contributions of
      Ayurveda masters.
AB  - Ayurveda, the native healthcare system of India, is a rich resource of well
      documented ancient medical knowledge. Although the roots of this knowledge date
      back to the Vedic and post-Vedic eras, it is generally believed that a dedicated
      branch for healthcare was gradually established approximately between 400 BCE and
      200 CE. Probably because the language of documentation of these early textbooks
      is in Sanskrit, a language that is not in day-to-day use among the general
      population even in India, many significant contributions of Ayurveda have
      remained unrecognized in the literature related to the history of medicine. In
      this communication, the discovery of blood circulation has been taken up as a
      case, and a few important references from the representative Ayurveda compendia
      that hint at a preliminary understanding of the cardiovascular system as a
      "closed circuit" and the heart acting as a pump have been reviewed. The central
      argument of this review is that these contributions from Ayurveda too must be
      recorded and credited when reviewing the milestones in the history of medicine,
      as Ayurveda can still possibly guide various streams of the current sciences, if
      revisited with this spirit.

PMID- 22665420
TI  - In pursuit of scientific excellence: sex matters.

PMID- 22665421
TI  - Analysis of variance: variably complex.

PMID- 22665422
TI  - Categorized or continuous? Strength of an association-and linear regression.

PMID- 22665423
TI  - Variation: use it or misuse it-replication and its variants.

PMID- 22665424
TI  - Can a tablet device alter undergraduate science students' study behavior and use
      of technology?
AB  - This article reports findings from a study investigating undergraduate biological
      sciences students' use of technology and computer devices for learning and the
      effect of providing students with a tablet device. A controlled study was
      conducted to collect quantitative and qualitative data on the impact of a tablet
      device on students' use of devices and technology for learning. Overall, we found
      that students made extensive use of the tablet device for learning, using it in
      preference to laptop computers to retrieve information, record lectures, and
      access learning resources. In line with other studies, we found that
      undergraduate students only use familiar Web 2.0 technologies and that the tablet
      device did not alter this behavior for the majority of tools. We conclude that
      undergraduate science students can make extensive use of a tablet device to
      enhance their learning opportunities without institutions changing their teaching
      methods or computer systems, but that institutional intervention may be needed to
      drive changes in student behavior toward the use of novel Web 2.0 technologies.

PMID- 22665425
TI  - Assessment outcome is weakly correlated with lecture attendance: influence of
      learning style and use of alternative materials.
AB  - The relation between lecture attendance and learning is surprisingly weak, and
      the role of learning styles in this is poorly understood. We hypothesized that 1)
      academic performance is related to lecture attendance and 2) learning style
      influences lecture attendance and, consequently, affects performance. We also
      speculated that the availability of alternative resources would affect this
      relationship. Second-year Bachelor of Science physiology students (n = 120) self
      reported their lecture attendance in a block of 21 lectures (attendance not
      compulsory) and use of alternative resources. Overall self-reported lecture
      attendance was 73 +/- 2%. Female students (n = 71) attended more lectures (16.4
      +/- 0.6) than male students (14.3 +/- 0.08, n = 49) and achieved a higher
      composite mark in all assessments (73.6% vs. 69.3%, P < 0.02). Marks in the final
      exam were not statistically different between the sexes and correlated only
      weakly with lecture attendance (r = 0.29, n = 49, P < 0.04 for male students; r =
      0.10, n = 71, P = not significant for female students; and r =0.21, n = 120, P <
      0.02 for the whole class). Of the students who passed the exam, poor attenders
      (<11 lectures) reported significantly more use of lecture recordings (37 +/- 8%,
      n = 15, vs. 10 +/- 1%, n = 85, P < 0.001). In a VARK learning style assessment
      (where V is visual, A is auditory, R is reading/writing, and K is kinesthetic),
      students were multimodal, although female students had a slightly higher average
      percentage of the R learning style (preferred read/write) compared with male
      students (28.9 +/- 0.9%, n = 63, vs. 25.3 +/- 1.3%, n = 32, P < 0.03). Lecture
      attendance was not correlated with measured learning style. We concluded that
      lecture attendance is only weakly correlated with academic performance and is not
      related to learning style. The substitution of alternative materials for lecture
      attendance appears to have a greater role than learning style in determining
      academic outcomes.

PMID- 22665426
TI  - Active physiology learning in a diverse class: an analysis of medical student
      responses in terms of sex, home language, and self-reported test performance.
AB  - The student body at the Nelson R. Mandela School of Medicine (NRMSM) is very
      diverse, representing many cultures, religions, and languages. Research has shown
      that weakness in English can impact student performance. Recent studies have also
      highlighted sex-based differences in students' learning and listening styles.
      These factors pose both challenges and opportunities for teachers of physiology.
      Student presentations were incorporated for a number of years into the
      traditional didactic second-year medical physiology curriculum at the NRMSM.
      Feedback obtained about the perceived benefits of these presentations for the
      learning of gastrointestinal and endocrine physiology included demographic data
      pertaining to students' sex, home language, and self-reported performance in
      tests. Analysis of the 50-item questionnaire responses, obtained over a 2-yr
      period, provided some interesting insights. Student responses to the items
      differed significantly in 27 of the 50 items in the questionnaire, based on sex
      alone (22%), sex and home language (7%), home language alone (37%), performance
      alone (26%), and performance and home language (7%). Our analyses of student
      perceptions support the findings of other studies and show that factors such as
      sex, home language, and student performance can play an important role in the way
      students are motivated to learn. In designing active learning strategies,
      academics need to take into account the potential influences that might affect
      student learning in diverse, multicultural, and multilingual classes.

PMID- 22665427
TI  - Showercap Mindmap: a spatial activity for learning physiology terminology and
      location.
AB  - Students struggle with the volume and complexity of physiology terminology. We
      compared first-year undergraduate psychology students' learning of physiological
      terms using two teaching methods: one verbal (control group; n = 16) and one
      spatial and multisensory (experimental group; n = 19). The experimental group
      used clear plastic shower caps to mark brain regions and affix labels to another
      participant's head. The control group learned the material verbally through a
      game. When tested verbally, both the control and experimental groups recalled
      more of the 10 terms immediately after the activity (+106% and +83%,
      respectively) and 2 wk later (+53% and +31%, respectively) than at the pretest (P
      < 0.0005). When participants' knowledge was tested spatially (labeling a brain
      diagram), the experimental group recalled more terms at the posttest (+76%) and
      followup (+73%) than at the pretest (P < 0.0005), but the control group who
      showed no improvement at either time point (+12% and +14%, respectively). These
      findings support the notion that spatial and multisensory learning produces
      improved spatial recall over time while also supporting the notion of transfer
      appropriate processing.

PMID- 22665428
TI  - Investigating high school students' conceptualizations of the biological basis of
      learning.
AB  - Students go to school to learn. How much, however, do students understand about
      the biological basis of this everyday process? Blackwell et al. (1) demonstrated
      a correlation between education about learning and academic achievement. Yet
      there are few studies investigating high school students' conceptions of
      learning. In this mixed-methods research study, written assessments were
      administered to 339 high school students in an urban school district after they
      completed their required biology education, and videotaped interviews were
      conducted with 15 students. The results indicated that the majority of students
      know little about the biological basis of learning, even with prompting, and they
      recall having learned little about it in school. Students appear to believe that
      people control their own ability to learn, and some have developed personal
      hypotheses to describe the learning process. On written assessments, 75% of
      participants demonstrated a nonbiological framework for learning, and, during
      interviews, 67% of participants revealed misconceptions about the biological
      basis of learning. Sample quotes of these interviews are included in this report,
      and the implications of these findings are discussed.

PMID- 22665429
TI  - What is the optimum duration of an asynchronous distance learning course?
AB  - An online, lecture/laboratory course in Human Physiology was run in two sections
      in five consecutive summers. In each year, the two sections were identical in
      content, assignments, and assessments but were different in duration; the shorter
      section was 1 mo and the longer section lasted 2 mo. The shorter section had a
      higher enrollment and a higher attrition rate. A postcourse survey revealed that
      the majority of the students in the shorter course believed that they would have
      spent more time studying and would have received a better grade had they taken
      the longer class. Interestingly, in any one year, there was no significant
      difference between the mean final grades earned by students in the two sections
      and by males and females. All students who completed the longer section and the
      majority of students in the shorter section of the course stated that they would
      recommend the longer class to a friend who was committed to taking this online
      course.

PMID- 22665430
TI  - Teaching baroreflex physiology to medical students: a comparison of quiz-based
      and conventional teaching strategies in a laboratory exercise.
AB  - Quiz-based and collaborative teaching strategies have previously been found to be
      efficient for the improving meaningful learning of physiology during lectures.
      These approaches have, however, not been investigated during laboratory
      exercises. In the present study, we compared the impact of solving quizzes
      individually and in groups with conventional teaching on the immediate learning
      during a laboratory exercise. We implemented two quizzes in a mandatory 4-h
      laboratory exercise on baroreflex physiology. A total of 155 second-year medical
      students were randomized to solve quizzes individually (intervention group I, n =
      57), in groups of three to four students (intervention group II, n = 56), or not
      to perform any quizzes (control; intervention group III, n = 42). After the
      laboratory exercise, all students completed an individual test, which encompassed
      two recall questions, two intermediate questions, and two integrated questions.
      The integrated questions were of moderate and advanced difficulty, respectively.
      Finally, students completed an evaluation form. Intervention group I reached the
      highest total test scores and proved best at answering the integrated question of
      advanced difficulty. Moreover, there was an overall difference between groups for
      student evaluations of the quality of the teaching, which was highest for
      intervention group II. In conclusion, solving quizzes individually during a
      laboratory exercise may enhance learning, whereas solving quizzes in groups is
      associated with higher student satisfaction.

PMID- 22665431
TI  - Multiweek cell culture project for use in upper-level biology laboratories.
AB  - This article describes a laboratory protocol for a multiweek project piloted in a
      new upper-level biology laboratory (BIO 426) using cell culture techniques. Human
      embryonic kidney-293 cells were used, and several culture media and supplements
      were identified for students to design their own experiments. Treatments included
      amino acids, EGF, caffeine, epinephrine, heavy metals, and FBS. Students
      researched primary literature to determine their experimental variables, made
      their own solutions, and treated their cells over a period of 2 wk. Before this,
      a sterile technique laboratory was developed to teach students how to work with
      the cells and minimize contamination. Students designed their experiments, mixed
      their solutions, seeded their cells, and treated them with their control and
      experimental media. Students had the choice of manipulating a number of
      variables, including incubation times, exposure to treatment media, and
      temperature. At the end of the experiment, students observed the effects of their
      treatment, harvested and dyed their cells, counted relative cell numbers in
      control and treatment flasks, and determined the ratio of living to dead cells
      using a hemocytometer. At the conclusion of the experiment, students presented
      their findings in a poster presentation. This laboratory can be expanded or
      adapted to include additional cell lines and treatments. The ability to design
      and implement their own experiments has been shown to increase student engagement
      in the biology-related laboratory activities as well as develop the critical
      thinking skills needed for independent research.

PMID- 22665432
TI  - Enhancing learning objectives by use of simple virtual microscopic slides in
      cellular physiology and histology: impact and attitudes.
AB  - The impact and perception of students on the use of a simple, low technology
      driven version of a virtual microscope in teaching and assessments in cellular
      physiology and histology were studied. Its impact on the time and resources of
      the faculty were also assessed. Simple virtual slides and conventional
      microscopes were used to conduct the same examinations for the same students.
      Students performed significantly better in the examination with the virtual slide
      and also showed a significantly higher preference for virtual slides. The time
      and cost implications of conducting examinations using the simple virtual slides
      were reduced by >1,400%. The results reemphasize the need for the design and
      adoption of simple sustainable technological innovations in developing countries
      to bridge gaps in purposeful learning environments.

PMID- 22665433
TI  - Differences between African-American and Caucasian students on enrollment
      influences and barriers in kinesiology-based allied health education programs.
AB  - Kinesiology departments have recently started to offer allied health education
      programs to attract additional students to teacher education units (9). Although
      allied health professions offer increased work opportunities, insufficient
      enrollment and training of minority students in these academic fields contribute
      to underrepresentation in the workforce (3). To improve workforce diversity,
      kinesiology departments must understand how enrollment influences and barriers
      differ by race among prospective students. Therefore, the purpose of this study
      was to identify differences in allied health education enrollment influences and
      enrollment barriers between minority and Caucasian students. Participants (n =
      601) consisted of students enrolled in kinesiology-based allied health education
      programs. Multivariate ANOVA was used to compare group differences in enrollment
      decision making. "Personal influence," "career opportunity," and "physical self
      efficacy" were all significantly stronger enrollment influences among African
      American students than among Caucasian students, and "social influence,"
      "experiential opportunity," "academic preparation," and "physical self-efficacy"
      were all perceived as significantly greater barriers compared with Caucasian
      students. Findings support the need to recruit African-American students through
      sport and physical education settings and to market program-based experiential
      opportunities.

PMID- 22665434
TI  - A simple model to demonstrate the balance of forces at functional residual
      capacity.

PMID- 22665435
TI  - Using scatterplots to teach the critical power concept.

PMID- 22665436
TI  - Feeling wall tension in an interactive demonstration of Laplace's law.

PMID- 22665437
TI  - Factors related to posttraumatic stress disorder in adolescence.
AB  - Studies of posttraumatic stress disorder (PTSD) in adolescence published from
      2000 to 2011 indicate that adolescents are at greater risk of experiencing trauma
      than either adults or children, and that the prevalence of PTSD among adolescents
      is 3-57%. Age, gender, type of trauma, and repeated trauma are discussed as
      factors related to the increased rates of adolescent PTSD. PTSD in adolescence is
      also associated with suicide, substance abuse, poor social support, academic
      problems, and poor physical health. PTSD may disrupt biological maturational
      processes and contribute to the long-term emotion and behavior regulation
      problems that are often evident in adolescents with the disorder. Recommendations
      are presented for practice and research regarding the promotion of targeted
      prevention and intervention services to maximize adolescents' strengths and
      minimize vulnerabilities. Public policy implications are discussed.

PMID- 22665438
TI  - Seed cone anatomy of Cheirolepidiaceae (Coniferales): reinterpreting Pararaucaria
      patagonica Wieland.
AB  - PREMISE OF THE STUDY: Seed cone morphology and anatomy reflect some of the most
      important changes in the phylogeny and evolutionary biology of conifers.
      Reexamination of the enigmatic Jurassic seed cone Pararaucaria patagonica reveals
      previously unknown systematically informative characters that demonstrate
      affinities with the Cheirolepidiaceae. This paper documents, for the first time,
      internal anatomy for seed cones of this important extinct Mesozoic conifer
      family, which may represent the ghost lineage leading to modern Pinaceae.
      METHODS: Morphology and anatomy of cones from the Jurassic La Matilde Formation
      in Patagonia are described from a combination of polished wafers and thin section
      preparations. New photographic techniques are employed to reveal histological
      details of thin sections in which organic cell wall remains are not preserved.
      Specific terminology for conifer seed cones is proposed to help clarify
      hypotheses of homology for the various structures of the cones. KEY RESULTS:
      Specimens are demonstrated to have trilobed ovuliferous scale tips along with a
      seed enclosing pocket of ovuliferous scale tissue. Originally thought to
      represent a seed wing in P. patagonica, this pocket-forming tissue is comparable
      to the flap of tissue covering seeds of compressed cheirolepidiaceous cones and
      is probably the most diagnostic character for seed cones of the family.
      CONCLUSIONS: Pararaucaria patagonica is assigned to Cheirolepidiaceae,
      documenting anatomical features for seed cones of the family and providing
      evidence for the antiquity of pinoid conifers leading to the origin of Pinaceae.
      A list of key morphological and anatomical characters for seed cones of
      Cheirolepidiaceae is developed to facilitate assignment of a much broader range
      of fossil remains to the family. This confirms the presence of Cheirolepidiaceae
      in the Jurassic of the Southern Hemisphere, which was previously suspected from
      palynological records.

PMID- 22665439
TI  - Deficiencies persist in the experience of UK vascular trainees: a survey of
      Rouleaux Club members.
AB  - AIMS: To evaluate the training experience of the current United Kingdom (UK)
      vascular trainees. METHODS: A Web-based questionnaire was administered to 217
      members of the Rouleaux Club, which represents UK vascular and endovascular
      trainees, between May and June 2011. RESULTS: A total of 153 trainees (71%
      response rate) completed the survey; 52% were in posts that do not offer
      endovascular training, 88% performed <10 peripheral angiograms, and 67% performed
      part or all of <10 endovascular aneurysm repairs in the last year. Half had no
      access to formal ultrasound training; 85% believe that vascular access will play
      a role in their future practice, but 49% performed no vascular access procedures
      in the past year. No experience of endovenous laser, radiofrequency ablation, or
      foam sclerotherapy was reported by 33%, 49%, and 46%, respectively. CONCLUSIONS:
      Trainee experience is insufficient for a modern specialist practice. Separate
      specialty training in the United Kingdom must address these deficiencies.

PMID- 22665440
TI  - Integrative functional genomics identifies an enhancer looping to the SOX9 gene
      disrupted by the 17q24.3 prostate cancer risk locus.
AB  - Genome-wide association studies (GWAS) are identifying genetic predisposition to
      various diseases. The 17q24.3 locus harbors the single nucleotide polymorphism
      (SNP) rs1859962 that is statistically associated with prostate cancer (PCa). It
      defines a 130-kb linkage disequilibrium (LD) block that lies in an ~2-Mb gene
      desert area. The functional biology driving the risk associated with this LD
      block is unknown. Here, we integrate genome-wide chromatin landscape data sets,
      namely, epigenomes and chromatin openness from diverse cell types. This
      identifies a PCa-specific enhancer within the rs1859962 risk LD block that
      establishes a 1-Mb chromatin loop with the SOX9 gene. The rs8072254 and rs1859961
      SNPs mapping to this enhancer impose allele-specific gene expression. The variant
      allele of rs8072254 facilitates androgen receptor (AR) binding driving increased
      enhancer activity. The variant allele of rs1859961 decreases FOXA1 binding while
      increasing AP-1 binding. The latter is key to imposing allele-specific gene
      expression. The rs8072254 variant in strong LD with the rs1859962 risk SNP can
      account for the risk associated with this locus, while rs1859961 is a rare
      variant less likely to contribute to the risk associated with this LD block.
      Together, our results demonstrate that multiple genetic variants mapping to a
      unique enhancer looping to the SOX9 oncogene can account for the risk associated
      with the PCa 17q24.3 locus. Allele-specific recruitment of the transcription
      factors androgen receptor (AR) and activating protein-1 (AP-1) account for the
      increased enhancer activity ascribed to this PCa-risk LD block. This further
      supports the notion that an integrative genomics approach can identify the
      functional biology disrupted by genetic risk variants.

PMID- 22665441
TI  - Maintaining replication origins in the face of genomic change.
AB  - Origins of replication present a paradox to evolutionary biologists. As a
      collection, they are absolutely essential genomic features, but individually are
      highly redundant and nonessential. It is therefore difficult to predict to what
      extent and in what regard origins are conserved over evolutionary time. Here,
      through a comparative genomic analysis of replication origins and chromosomal
      replication patterns in the budding yeasts Saccharomyces cerevisiae and Lachancea
      waltii, we assess to what extent replication origins survived genomic change
      produced from 150 million years of evolution. We find that L. waltii origins
      exhibit a core consensus sequence and nucleosome occupancy pattern highly similar
      to those of S. cerevisiae origins. We further observe that the overall
      progression of chromosomal replication is similar between L. waltii and S.
      cerevisiae. Nevertheless, few origins show evidence of being conserved in
      location between the two species. Among the conserved origins are those
      surrounding centromeres and adjacent to histone genes, suggesting that proximity
      to an origin may be important for their regulation. We conclude that, over
      evolutionary time, origins maintain sequence, structure, and regulation, but are
      continually being created and destroyed, with the result that their locations are
      generally not conserved.

PMID- 22665444
TI  - Brittle culm15 encodes a membrane-associated chitinase-like protein required for
      cellulose biosynthesis in rice.
AB  - Plant chitinases, a class of glycosyl hydrolases, participate in various aspects
      of normal plant growth and development, including cell wall metabolism and
      disease resistance. The rice (Oryza sativa) genome encodes 37 putative chitinases
      and chitinase-like proteins. However, none of them has been characterized at the
      genetic level. In this study, we report the isolation of a brittle culm mutant,
      bc15, and the map-based cloning of the BC15/OsCTL1 (for chitinase-like1) gene
      affected in the mutant. The gene encodes the rice chitinase-like protein
      BC15/OsCTL1. Mutation of BC15/OsCTL1 causes reduced cellulose content and
      mechanical strength without obvious alterations in plant growth. Bioinformatic
      analyses indicated that BC15/OsCTL1 is a class II chitinase-like protein that is
      devoid of both an amino-terminal cysteine-rich domain and the chitinase activity
      motif H-E-T-T but possesses an amino-terminal transmembrane domain. Biochemical
      assays demonstrated that BC15/OsCTL1 is a Golgi-localized type II membrane
      protein that lacks classical chitinase activity. Quantitative real-time
      polymerase chain reaction and beta-glucuronidase activity analyses indicated that
      BC15/OsCTL1 is ubiquitously expressed. Investigation of the global expression
      profile of wild-type and bc15 plants, using Illumina RNA sequencing, further
      suggested a possible mechanism by which BC15/OsCTL1 mediates cellulose
      biosynthesis and cell wall remodeling. Our findings provide genetic evidence of a
      role for plant chitinases in cellulose biosynthesis in rice, which appears to
      differ from their roles as revealed by analysis of Arabidopsis (Arabidopsis
      thaliana).

PMID- 22665443
TI  - Human genomic disease variants: a neutral evolutionary explanation.
AB  - Many perspectives on the role of evolution in human health include nonempirical
      assumptions concerning the adaptive evolutionary origins of human diseases.
      Evolutionary analyses of the increasing wealth of clinical and population genomic
      data have begun to challenge these presumptions. In order to systematically
      evaluate such claims, the time has come to build a common framework for an
      empirical and intellectual unification of evolution and modern medicine. We
      review the emerging evidence and provide a supporting conceptual framework that
      establishes the classical neutral theory of molecular evolution (NTME) as the
      basis for evaluating disease- associated genomic variations in health and
      medicine. For over a decade, the NTME has already explained the origins and
      distribution of variants implicated in diseases and has illuminated the power of
      evolutionary thinking in genomic medicine. We suggest that a majority of disease
      variants in modern populations will have neutral evolutionary origins (previously
      neutral), with a relatively smaller fraction exhibiting adaptive evolutionary
      origins (previously adaptive). This pattern is expected to hold true for common
      as well as rare disease variants. Ultimately, a neutral evolutionary perspective
      will provide medicine with an informative and actionable framework that enables
      objective clinical assessment beyond convenient tendencies to invoke past
      adaptive events in human history as a root cause of human disease.

PMID- 22665445
TI  - Xyloglucan xylosyltransferases XXT1, XXT2, and XXT5 and the glucan synthase CSLC4
      form Golgi-localized multiprotein complexes.
AB  - Xyloglucan is the major hemicellulosic polysaccharide in the primary cell walls
      of most vascular dicotyledonous plants and has important structural and
      physiological functions in plant growth and development. In Arabidopsis
      (Arabidopsis thaliana), the 1,4-beta-glucan synthase, Cellulose Synthase-Like C4
      (CSLC4), and three xylosyltransferases, XXT1, XXT2, and XXT5, act in the Golgi to
      form the xylosylated glucan backbone during xyloglucan biosynthesis. However, the
      functional organization of these enzymes in the Golgi membrane is currently
      unknown. In this study, we used bimolecular fluorescence complementation and in
      vitro pull-down assays to investigate the supramolecular organization of the
      CSLC4, XXT1, XXT2, and XXT5 proteins in Arabidopsis protoplasts. Quantification
      of bimolecular fluorescence complementation fluorescence by flow cytometry
      allowed us to perform competition assays that demonstrated the high probability
      of protein-protein complex formation in vivo and revealed differences in the
      abilities of these proteins to form multiprotein complexes. Results of in vitro
      pull-down assays using recombinant proteins confirmed that the physical
      interactions among XXTs occur through their catalytic domains. Additionally,
      coimmunoprecipitation of XXT2YFP and XXT5HA proteins from Arabidopsis protoplasts
      indicated that while the formation of the XXT2-XXT2 homocomplex involves
      disulfide bonds, the formation of the XXT2-XXT5 heterocomplex does not involve
      covalent interactions. The combined data allow us to propose that the proteins
      involved in xyloglucan biosynthesis function in a multiprotein complex composed
      of at least two homocomplexes, CSLC4-CSLC4 and XXT2-XXT2, and three
      heterocomplexes, XXT2-XXT5, XXT1-XXT2, and XXT5-CSLC4.

PMID- 22665446
TI  - Infestation and hydraulic consequences of induced carbon starvation.
AB  - Drought impacts on forests, including widespread die-off, are likely to increase
      with future climate change, although the physiological responses of trees to
      lethal drought are poorly understood. In particular, in situ examinations of
      carbon starvation and its interactions with and effects on infestation and
      hydraulic vulnerability are largely lacking. In this study, we conducted a
      controlled, in situ, repeated defoliation experiment to induce carbon stress in
      isolated trembling aspen (Populus tremuloides) ramets. We monitored leaf
      morphology, leaves per branch, and multitissue carbohydrate concentrations during
      canopy defoliation. We examined the subsequent effects of defoliation and
      defoliation-induced carbon stress on vulnerability to insect/fungus infestation
      and hydraulic vulnerability the following year. Defoliated ramets flushed
      multiple canopies, which coincided with moderate drawdown of nonstructural
      carbohydrate reserves. Infestation frequency greatly increased and hydraulic
      conductivity decreased 1 year after defoliation. Despite incomplete carbohydrate
      drawdown from defoliation and relatively rapid carbohydrate recovery, suggesting
      considerable carbohydrate reserves in aspen, defoliation-induced carbon stress
      held significant consequences for vulnerability to mortality agents and hydraulic
      performance. Our results indicate that multiyear consequences of drought via
      feedbacks are likely important for understanding forests' responses to drought
      and climate change over the coming decades.

PMID- 22665447
TI  - Classification and stratification of primary progressive aphasia: CSF biomarkers
      as a useful tool?

PMID- 22665448
TI  - Immune-mediated neuropathies induced by immunosuppressive treatment.

PMID- 22665449
TI  - Impact commentaries. Observations on 500 cases of migraine and allied vascular
      headache.

PMID- 22665442
TI  - Identifying genomic and metabolic features that can underlie early successional
      and opportunistic lifestyles of human gut symbionts.
AB  - We lack a deep understanding of genetic and metabolic attributes specializing in
      microbial consortia for initial and subsequent waves of colonization of our body
      habitats. Here we show that phylogenetically interspersed bacteria in Clostridium
      cluster XIVa, an abundant group of bacteria in the adult human gut also known as
      the Clostridium coccoides or Eubacterium rectale group, contains species that
      have evolved distribution patterns consistent with either early successional or
      stable gut communities. The species that specialize to the infant gut are more
      likely to associate with systemic infections and can reach high abundances in
      individuals with Inflammatory Bowel Disease (IBD), indicating that a subset of
      the microbiota that have adapted to pioneer/opportunistic lifestyles may do well
      in both early development and with disease. We identified genes likely selected
      during adaptation to pioneer/opportunistic lifestyles as those for which early
      succession association and not phylogenetic relationships explain genomic
      abundance. These genes reveal potential mechanisms by which opportunistic gut
      bacteria tolerate osmotic and oxidative stress and potentially important aspects
      of their metabolism. These genes may not only be biomarkers of properties
      associated with adaptation to early succession and disturbance, but also leads
      for developing therapies aimed at promoting reestablishment of stable gut
      communities following physiologic or pathologic disturbances.

PMID- 22665450
TI  - Distinct brain perfusion pattern associated with CSF biomarkers profile in
      primary progressive aphasia.
AB  - OBJECTIVE: A new classification of primary progressive aphasia (PPA) was recently
      proposed to differentiate between non-fluent aphasia (NF-PPA), semantic variant
      of PPA (S-PPA) and logopenic aphasia (LPA) by their phenotypic presentations. CSF
      biomarkers (BM) may differentiate PPA with atypical Alzheimer's disease (AD) that
      presents with LPA from PPA with frontotemporal lobe degeneration that presents
      with either NF-PPA or S-PPA. Single photon emission computed tomography (SPECT)
      was used to investigate brain hypoperfusion differences among PPA subtypes
      according to their CSF AD profiles. METHODS: 34 PPA patients underwent lumbar
      puncture and brain perfusion SPECT. PPA patients were classified into two
      subgroups according to the Abeta(42):tau ratio: PPA BM positive (with an AD CSF
      profile) and PPA BM negative (not having an AD CSF profile). The biological
      classification was made while blind to the phenotypical presentation. The brain
      perfusion profiles of the PPA subgroups were compared with those of 24 healthy
      subjects. RESULTS: PPA BM positive patients had left-side predominant
      hypoperfusion in the temporoparietal cortex that extended to the dorsolateral
      prefrontal cortex and perisylvian region while PPA BM negative patients had
      hypoperfusion that was predominant in the temporal poles (p<10(-4) corrected).
      CONCLUSION: Distinct hypoperfusion patterns in PPA BM positive and PPA BM
      negative patients were observed, similar to those that have been described for S
      PPA and LPA. These results support using CSF biomarkers to classify PPA.

PMID- 22665451
TI  - Mortality in a cohort of patients with psychogenic non-epileptic seizures.
AB  - Some evidence suggests that psychogenic non-epileptic seizures (PNES) are
      associated with increased mortality. The authors obtained death certificate
      information in a cohort of 260 patients who presented with PNES between 1999 and
      2004. The follow-up period averaged 7.92 years, during which 17 patients died,
      12/17 were under the age of 75 years, giving a premature (<75 years) mortality
      rate of 0.58%, compared with a Scottish mortality rate for the 40-75 years age
      group of 0.41% per year. The main predictor of death was the patient age at
      presentation of PNES. There was no correlation with withdrawal of anticonvulsant
      medication, and death certificate information provided no evidence to suggest
      that the deaths were related to the seizure disorder. The population had a high
      mean deprivation rank, providing a possible explanation for a modest increase in
      premature death rate.

PMID- 22665456
TI  - Perisaccadic compression in two-saccade sequences.
AB  - Around the onset of a saccade toward a target, localization judgments are
      systematically biased toward the saccade endpoint. This perisaccadic compression
      is thought to be related to transsaccadic reorganization and due to interfering
      motor signals in visual maps. It has, however, only been investigated for
      saccades targeting a single target. Here, we examined whether saccade-sequence
      programming to stationary target(s) would affect the pattern of localization
      judgments of a briefly flashed stimulus. We presented saccade targets that could
      induce either a single saccade or two-saccade sequences and we flashed a bar
      around saccade onsets. For all two-saccade-sequence conditions, we showed that
      localization judgments of the stimulus flashed around the first saccade onset are
      biased toward an intermediate position between the two-saccade landing position,
      indicating the influence of the second saccade's parallel planning. This implies
      that motor-planning signals are most likely responsible for perisaccadic
      compression than motor execution feedback.

PMID- 22665457
TI  - A new spectrally sharpened sensor basis to predict color naming, unique hues, and
      hue cancellation.
AB  - When light is reflected off a surface, there is a linear relation between the
      three human photoreceptor responses to the incoming light and the three
      photoreceptor responses to the reflected light. Different colored surfaces have
      different linear relations. Recently, Philipona and O'Regan (2006) showed that
      when this relation is singular in a mathematical sense, then the surface is
      perceived as having a highly nameable color. Furthermore, white light reflected
      by that surface is perceived as corresponding precisely to one of the four
      psychophysically measured unique hues. However, Philipona and O'Regan's approach
      seems unrelated to classical psychophysical models of color constancy. In this
      paper we make this link. We begin by transforming cone sensors to spectrally
      sharpened counterparts. In sharp color space, illumination change can be modeled
      by simple von Kries type scalings of response values within each of the
      spectrally sharpened response channels. In this space, Philipona and O'Regan's
      linear relation is captured by a simple Land-type color designator defined by
      dividing reflected light by incident light. This link between Philipona and
      O'Regan's theory and Land's notion of color designator gives the model biological
      plausibility. We then show that Philipona and O'Regan's singular surfaces are
      surfaces which are very close to activating only one or only two of such newly
      defined spectrally sharpened sensors, instead of the usual three. Closeness to
      zero is quantified in a new simplified measure of singularity which is also shown
      to relate to the chromaticness of colors. As in Philipona and O'Regan's original
      work, our new theory accounts for a large variety of psychophysical color data.

PMID- 22665458
TI  - Number and density discrimination rely on a common metric: Similar psychophysical
      effects of size, contrast, and divided attention.
AB  - While observers are adept at judging the density of elements (e.g., in a random
      dot image), it has recently been proposed that they also have an independent
      visual sense of number. To test the independence of number and density
      discrimination, we examined the effects of manipulating stimulus structure (patch
      size, element size, contrast, and contrast-polarity) and available attentional
      resources on both judgments. Five observers made a series of two-alternative,
      forced-choice discriminations based on the relative numerosity/density of two
      simultaneously presented patches containing 16-1,024 Gaussian blobs. Mismatches
      of patch size and element size (across reference and test) led to bias and
      reduced sensitivity in both tasks, whereas manipulations of contrast and contrast
      polarity had varied effects on observers, implying differing strategies.
      Nonetheless, the effects reported were consistent across density and number
      judgments, the only exception being when luminance cues were made available.
      Finally, density and number judgment were similarly impaired by attentional load
      in a dual-task experiment. These results are consistent with a common underlying
      metric to density and number judgments, with the caveat that additional cues may
      be exploited when they are available.

PMID- 22665460
TI  - Superior vena cava syndrome caused by Hodgkin's lymphoma in an adolescent girl.
AB  - A 14-year-old female patient presented to us with complaints of shortness of
      breath, swelling over upper body and dysphagia, prominent veins were visible on
      upper body. CT scan of chest revealed a large mediastinal mass compressing
      surrounding structures. Histopathology and immunohistochemistry confirmed it to
      be Hodgkin's lymphoma. The patient was given a course of chemotherapy
      (doxorubicin, bleomycin, vinblastine and dacarabazine) and local radiotherapy.
      Presently she is doing well.

PMID- 22665461
TI  - A 20-year-old Chinese man with recurrent hypokalemic periodic paralysis and
      delayed diagnosis.
AB  - Periodic paralysis in the setting of hypokalemia can be the result of several
      underlying conditions, requiring systematic evaluation. Thyrotoxic periodic
      paralysis (TPP), a curable cause of hypokalemic periodic paralysis, can often be
      the first manifestation of thyrotoxicosis. Because the signs and symptoms of
      thyrotoxicosis can be subtle and clouded by the clinical distress of the patient,
      the diagnosis of the underlying metabolic disorder can be overlooked. The authors
      report a case of TPP in a young Chinese man in whom the diagnosis of
      thyrotoxicosis was initially missed. This case illustrates the lack of awareness
      of TPP among many physicians, delay in the diagnosis of TPP and the importance of
      performing thyroid function testing in all cases of periodic paralysis.

PMID- 22665462
TI  - Pulsatile abdominal mass is not always leaking aneurysm!
AB  - An 80-year-old male, who presented with a history of unprovoked collapse, was
      found to have a visible pulsation in the central upper abdomen, which disappeared
      on raising his arms above his shoulder ('head and shoulder' technique). There was
      no tenderness noted over the pulsation. He had a ventricular demand inhibited
      pacemaker inserted 3 weeks ago for a significant bradycardia with atrial
      fibrillation. His ECG showed heart rate of 32 bpm with underlying atrial
      fibrillation. No pacing spikes noted. His chest x-ray confirmed displacement of
      pacing lead into the right subclavian vein. It caused stimulation of phrenic
      nerve resulting in rhythmical diaphragmatic contraction. He later had his
      pacemaker re-inserted with no more collapses.

PMID- 22665463
TI  - Spontaneous perinatal epidural haemorrhage in a newborn.
AB  - A full-term neonate, born by caesarean section, presents with focal seizures. EEG
      and cranial ultrasound are normal. MRI of the cerebrum shows an epidural
      haematoma. Perinatal intracranial haemorrhage in the full-term newborn is an
      important cause of morbidity and mortality. Most perinatal intracranial
      haemorrhages are located either subdural or intracerebral, rarely epidural.
      Epidural haemorrhage is usually a complication of assisted delivery, however it
      may also occur without forcipal or vacuum extraction, as demonstrated in this
      case. An epidural haemorrhage should be suspected on clinical findings, even in
      the absence of an assisted delivery. As cranial ultrasound sonography often
      misses epidural haemorrhage due to parietal location of the haemorrhage, the
      diagnosis needs either cerebral CT or MRI.

PMID- 22665464
TI  - Splenic vein aneurysm.

PMID- 22665465
TI  - Genital ulcers: do not forget Behcet disease.

PMID- 22665466
TI  - Erythema multiforme: a simple rash or sinister sign?

PMID- 22665467
TI  - Reversible lesion in the splenium of the corpus callosum associated with
      Legionnaires' pneumonia.

PMID- 22665468
TI  - H1N1 infection associated with persistent lower respiratory tract illness in an
      infant with isolated IgA deficiency.
AB  - Persistent pneumonia associated with H1N1 influenza infection is a rarely
      reported clinical entity. The authors describe the case of an infant who
      presented to the emergency department with respiratory distress and a 30-day
      history of intermittent cough and breathing difficulty. Low grade gastro
      oesophageal reflux (GER) was a possible cause for the patient's persistent lower
      respiratory tract symptoms. However, despite appropriate and adequate therapy for
      GER, his symptoms persisted and he worsened a week after admission. A search for
      causes of persistent pneumonia showed positive results for H1N1 virus and
      isolated IgA deficiency. IgA deficiency in an infant with H1N1 infection has not
      been previously reported. Inability to mount an adequate local immune response
      due to deficiency of the antibody could have led to the persistence of symptoms
      in this case. Screening of family members for the source of infection revealed
      that the mother was positive for the virus. The authors report this case to
      highlight the need to rule out underlying IgA deficiency in children with an
      atypical course of H1N1 pneumonia.

PMID- 22665469
TI  - Fallacious electrocardiographic interpretation in acute myocardial infarction.

PMID- 22665470
TI  - An unusual presentation of migraine: temporary complete body paralysis and
      aphasia.
AB  - A 47-year-old gentleman with a medical history of long-standing migraine
      presented with temporary total body paralysis and expressive aphasia for 4 h. It
      was also associated with worsening severe unilateral pulsating pain, nausea,
      photophobia, blurred vision, hearing disturbance and neck stiffness. All these
      symptoms were resolving gradually after 4 h and had resolved completely after 1
      day. Investigations were unremarkable. Migraine was made as a diagnosis of
      exclusion.

PMID- 22665471
TI  - Lipoma of the pinnal helix: a very unusual location for a very common tumour.
AB  - Lipomas are common benign tumours but can present in unusual locations. The
      authors present the rare case of a pedunculated lipoma of the pinnal helix. The
      lipoma was excised with good cosmetic result. Lipoma of the cartilaginous pinnal
      helix is rare and has not been described previously in the literature.

PMID- 22665472
TI  - Gallstone ileus.

PMID- 22665473
TI  - Coincident intra-abdominal presentation of lymphoma and tuberculosis after long
      term iatrogenic immunosuppression.

PMID- 22665474
TI  - Aortic valve replacement in a Jehovah's Witness: a case of multi-disciplinary
      clinical management for bloodless surgery.
AB  - An 81-year-old female Jehovah's Witness (JW) patient with severe aortic stenosis
      required aortic valve replacement (AVR). However, the patient's religious beliefs
      precluded the use of primary blood components. Since the definitive treatment of
      AVR required bloodless open heart surgery, careful peri-operative plans were set
      forth by a multi-disciplinary team involving the cardiothoracic surgeon,
      haematologist and anaesthetist. The patient went on to successfully recover
      postoperatively. This case highlights: 1) The importance of carefully navigating
      through the most recent clinical and ethical protocol involved in the surgical
      management of JW's. 2) The importance of preparing individually tailored pre,
      intra and postoperative plans that are delivered through a multi-disciplinary
      clinical team to ensure the best and safest possible outcomes.

PMID- 22665475
TI  - A dual role for receptor-interacting protein kinase 2 (RIP2) kinase activity in
      nucleotide-binding oligomerization domain 2 (NOD2)-dependent autophagy.
AB  - Autophagy is triggered by the intracellular bacterial sensor NOD2 (nucleotide
      binding, oligomerization domain 2) as an anti-bacterial response. Defects in
      autophagy have been implicated in Crohn's disease susceptibility. The molecular
      mechanisms of activation and regulation of this process by NOD2 are not well
      understood, with recent studies reporting conflicting requirements for RIP2
      (receptor-interacting protein kinase 2) in autophagy induction. We examined the
      requirement of NOD2 signaling mediated by RIP2 for anti-bacterial autophagy
      induction and clearance of Salmonella typhimurium in the intestinal epithelial
      cell line HCT116. Our data demonstrate that NOD2 stimulates autophagy in a
      process dependent on RIP2 tyrosine kinase activity. Autophagy induction requires
      the activity of the mitogen-activated protein kinases MEKK4 and p38 but is
      independent of NFkappaB signaling. Activation of autophagy was inhibited by a
      PP2A phosphatase complex, which interacts with both NOD2 and RIP2. PP2A
      phosphatase activity inhibited NOD2-dependent autophagy but not activation of
      NFkappaB or p38. Upon stimulation of NOD2, the phosphatase activity of the PP2A
      complex is inhibited through tyrosine phosphorylation of the catalytic subunit in
      a process dependent on RIP2 activity. These findings demonstrate that RIP2
      tyrosine kinase activity is not only required for NOD2-dependent autophagy but
      plays a dual role in this process. RIP2 both sends a positive autophagy signal
      through activation of p38 MAPK and relieves repression of autophagy mediated by
      the phosphatase PP2A.

PMID- 22665476
TI  - Conserved intergenic elements and DNA methylation cooperate to regulate
      transcription at the il17 locus.
AB  - Naive CD4(+) T cells can differentiate into distinct lineages with unique immune
      functions. The cytokines TGFbeta and IL-6 promote the development of Th17 cells
      that produce IL-17, an inflammatory cytokine not expressed by other T helper
      lineages. To further understand how IL-17 production is controlled, we studied an
      ~120-kb genomic region containing the murine il17a and il17f genes and seven
      evolutionarily conserved, intergenic noncoding sequences. We show that the +28-kb
      noncoding sequence cooperates with STAT3, RORgammat, and Runx1 to enhance
      transcription from both il17a and il17f promoters. This enhancer and both
      promoters exhibited Th17 lineage-specific DNA demethylation, accompanied by
      demethylation of lysine 27 of histone H3 (H3K27) and increased H3K4 methylation.
      Loss of DNA methylation tended to occur at STAT3 consensus elements, and we show
      that methylation of one of these elements in the il17a promoter directly inhibits
      STAT3 binding and transcriptional activity. These results demonstrate that
      TGFbeta and IL-6 synergize to epigenetically poise the il17 loci for expression
      in Th17 cells, and suggest a general mechanism by which active STAT3 may be
      epigenetically excluded from STAT3-responsive genes in non-Th17 lineages.

PMID- 22665477
TI  - Function of human alpha3beta4alpha5 nicotinic acetylcholine receptors is reduced
      by the alpha5(D398N) variant.
AB  - Genome-wide studies have strongly associated a non-synonymous polymorphism
      (rs16969968) that changes the 398th amino acid in the nAChR alpha5 subunit from
      aspartic acid to asparagine (D398N), with greater risk for increased nicotine
      consumption. We have used a pentameric concatemer approach to express defined and
      consistent populations of alpha3beta4alpha5 nAChR in Xenopus oocytes. alpha5(Asn
      398; risk) variant incorporation reduces ACh-evoked function compared with
      inclusion of the common alpha5(Asp-398) variant without altering agonist or
      antagonist potencies. Unlinked alpha3, beta4, and alpha5 subunits assemble to
      form a uniform nAChR population with pharmacological properties matching those of
      concatemeric alpha3beta4* nAChRs. alpha5 subunit incorporation reduces
      alpha3beta4* nAChR function after coinjection with unlinked alpha3 and beta4
      subunits but increases that of alpha3beta4alpha5 versus alpha3beta4-only
      concatemers. alpha5 subunit incorporation into alpha3beta4* nAChR also alters the
      relative efficacies of competitive agonists and changes the potency of the non
      competitive antagonist mecamylamine. Additional observations indicated that in
      the absence of alpha5 subunits, free alpha3 and beta4 subunits form at least two
      further subtypes. The pharmacological profiles of these free subunit alpha3beta4
      only subtypes are dissimilar both to each other and to those of alpha3beta4alpha5
      nAChR. The alpha5 variant-induced change in alpha3beta4alpha5 nAChR function may
      underlie some of the phenotypic changes associated with this polymorphism.

PMID- 22665478
TI  - Functional mapping of interacting regions of the photoreceptor phosphodiesterase
      (PDE6) gamma-subunit with PDE6 catalytic dimer, transducin, and regulator of G
      protein signaling9-1 (RGS9-1).
AB  - The cGMP phosphodiesterase (PDE6) involved in visual transduction in
      photoreceptor cells contains two inhibitory gamma-subunits (Pgamma) which bind to
      the catalytic core (Palphabeta) to inhibit catalysis and stimulate cGMP binding
      to the GAF domains of Palphabeta. During visual excitation, interaction of
      activated transducin with Pgamma relieves inhibition. Pgamma also participates in
      a complex with RGS9-1 and other proteins to accelerate the GTPase activity of
      activated transducin. We studied the structural determinants for these important
      functions of Pgamma. First, we identified two important sites in the middle
      region of Pgamma (amino acids 27-38 and 52-54) that significantly stabilize the
      overall binding affinity of Pgamma with Palphabeta. The ability of Pgamma to
      stimulate noncatalytic cGMP binding to the GAF domains of PDE6 has been localized
      to amino acids 27-30 of Pgamma. Transducin activation of PDE6 catalysis
      critically depends on the presence of Ile54 in the glycine-rich region of Pgamma
      in order to relieve inhibition of catalysis. The central glycine-rich region of
      Pgamma is also required for transducin to increase cGMP exchange at the GAF
      domains. Finally, Thr-65 and/or Val-66 of Pgamma are critical residues for Pgamma
      to stimulate GTPase activity of transducin in a complex with RGS9-1. We propose
      that the glycine-rich region of Pgamma is a primary docking site for PDE6
      interacting proteins involved in the activation/inactivation pathways of visual
      transduction. This functional mapping of Pgamma with its binding partners
      demonstrates the remarkable versatility of this multifunctional protein and its
      central role in regulating the activation and lifetime of visual transduction.

PMID- 22665479
TI  - Autolytic proteolysis within the function to find domain (FIIND) is required for
      NLRP1 inflammasome activity.
AB  - Nucleotide-binding domain leucine-rich repeat proteins (NLRs) play a key role in
      immunity and disease through their ability to modulate inflammation in response
      to pathogen-derived and endogenous danger signals. Here, we identify the
      requirements for activation of NLRP1, an NLR protein associated with a number of
      human pathologies, including vitiligo, rheumatoid arthritis, and Crohn disease.
      We demonstrate that NLRP1 activity is dependent upon ASC, which associates with
      the C-terminal CARD domain of NLRP1. In addition, we show that NLRP1 activity is
      dependent upon autolytic cleavage at Ser(1213) within the FIIND. Importantly,
      this post translational event is dependent upon the highly conserved distal
      residue His(1186). A disease-associated single nucleotide polymorphism near
      His(1186) and a naturally occurring mRNA splice variant lacking exon 14
      differentially affect this autolytic processing and subsequent NLRP1 activity.
      These results describe key molecular pathways that regulate NLRP1 activity and
      offer insight on how small sequence variations in NLR genes may influence human
      disease pathogenesis.

PMID- 22665480
TI  - Function of GRIM-19, a mitochondrial respiratory chain complex I protein, in
      innate immunity.
AB  - Mitochondria respiratory chain (RC), consisting of five multisubunit complexes,
      is crucial for cellular energy production, reactive oxygen species generation,
      and regulation of apoptosis. Recently, a few mitochondrial proteins have been
      reported to be essential for innate immunity, but the function of mitochondrial
      RC in innate immunity is largely unknown. By knock-out of GRIM-19, a newly
      identified subunit protein of mitochondrial complex I, in mice, we found that
      heterogeneous mice (GRIM-19(+/-)) are prone to spontaneous urinary tract
      infection, mostly by Staphylococcus saprophyticus. Macrophages derived from these
      mice have compromised mitochondrial complex I activity and increased reactive
      oxygen species level. Bacterial infection induces a rapid up-regulation of GRIM
      19 and complex I activity in the wild-type macrophages, but both are reduced in
      the macrophages from GRIM-19(+/-) mice. These cells also have decreased
      intracellular killing ability against S. saprophyticus. The defects for this
      probably occur in the fusion of bacteria to lysosome, but not in the bacterial
      engulfment and macrophage migration. In addition, production of proinflammatory
      cytokines, such as interleukin (IL)-1, IL-12, IL-6, and interferon (IFN)-gamma,
      induced by both bacterial infection and lipopolysaccharide (LPS) and
      monodansylcadaverine treatment, is also decreased in the GRIM19(+/-) macrophages.
      Inhibition of mitochondrial RC activity by inhibitors shows a similar reduction
      on the cytokine production. Due to low cytokine production, the inflammatory
      response caused by in vivo bacterial challenge in the bladders of GRIM-19(+/-)
      mice is compromised. This study provides genetic evidence for a critical role of
      mitochondrial RC in innate immunity.

PMID- 22665481
TI  - Disruption of mouse cytochrome p450 4f14 (Cyp4f14 gene) causes severe
      perturbations in vitamin E metabolism.
AB  - Vitamin E is a family of naturally occurring and structurally related lipophilic
      antioxidants, one of which, alpha-tocopherol (alpha-TOH), selectively accumulates
      in vertebrate tissues. The omega-hydroxylase cytochrome P450-4F2 (CYP4F2) is the
      only human enzyme shown to metabolize vitamin E. Using cDNA cloning, cell culture
      expression, and activity assays, we identified Cyp4f14 as a functional murine
      ortholog of CYP4F2. We then investigated the effect of Cyp4f14 deletion on
      vitamin E metabolism and status in vivo. Cyp4f14-null mice exhibited substrate
      specific reductions in liver microsomal vitamin E-omega-hydroxylase activity
      ranging from 93% (gamma-TOH) to 48% (gamma-tocotrienol). In vivo data obtained
      from metabolic cage studies showed whole-body reductions in metabolism of gamma
      TOH of 90% and of 68% for delta- and alpha-TOH. This metabolic deficit in
      Cyp4f14(-/-) mice was partially offset by increased fecal excretion of
      nonmetabolized tocopherols and of novel omega-1- and omega-2-hydroxytocopherols.
      12'-OH-gamma-TOH represented 41% of whole-body production of gamma-TOH
      metabolites in Cyp4f14(-/-) mice fed a soybean oil diet. Despite these
      counterbalancing mechanisms, Cyp4f14-null mice fed this diet for 6 weeks hyper
      accumulated gamma-TOH (2-fold increase over wild-type littermates) in all tissues
      and appeared normal. We conclude that CYP4F14 is the major but not the only
      vitamin E-omega-hydroxylase in mice. Its disruption significantly impairs whole
      body vitamin E metabolism and alters the widely conserved phenotype of
      preferential tissue deposition of alpha-TOH. This model animal and its
      derivatives will be valuable in determining the biological actions of specific
      tocopherols and tocotrienols in vivo.

PMID- 22665482
TI  - Lysophosphatidic acid activates lipogenic pathways and de novo lipid synthesis in
      ovarian cancer cells.
AB  - One of the most common molecular changes in cancer is the increased endogenous
      lipid synthesis, mediated primarily by overexpression and/or hyperactivity of
      fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). The changes in these
      key lipogenic enzymes are critical for the development and maintenance of the
      malignant phenotype. Previous efforts to control oncogenic lipogenesis have been
      focused on pharmacological inhibitors of FAS and ACC. Although they show anti
      tumor effects in culture and in mouse models, these inhibitors are nonselective
      blockers of lipid synthesis in both normal and cancer cells. To target lipid
      anabolism in tumor cells specifically, it is important to identify the mechanism
      governing hyperactive lipogenesis in malignant cells. In this study, we
      demonstrate that lysophosphatidic acid (LPA), a growth factor-like mediator
      present at high levels in ascites of ovarian cancer patients, regulates the
      sterol regulatory element binding protein-FAS and AMP-activated protein kinase
      ACC pathways in ovarian cancer cells but not in normal or immortalized ovarian
      epithelial cells. Activation of these lipogenic pathways is linked to increased
      de novo lipid synthesis. The pro-lipogenic action of LPA is mediated through
      LPA(2), an LPA receptor subtype overexpressed in ovarian cancer and other
      malignancies. Downstream of LPA(2), the G(12/13) and G(q) signaling cascades
      mediate LPA-dependent sterol regulatory element-binding protein activation and
      AMP-activated protein kinase inhibition, respectively. Moreover, inhibition of de
      novo lipid synthesis dramatically attenuated LPA-induced cell proliferation.
      These results demonstrate that LPA signaling is causally linked to the
      hyperactive lipogenesis in ovarian cancer cells, which can be exploited for
      development of new anti-cancer therapies.

PMID- 22665483
TI  - Structural basis for WDR5 interaction (Win) motif recognition in human SET1
      family histone methyltransferases.
AB  - Translocations and amplifications of the mixed lineage leukemia-1 (MLL1) gene are
      associated with aggressive myeloid and lymphocytic leukemias in humans. MLL1 is a
      member of the SET1 family of histone H3 lysine 4 (H3K4) methyltransferases, which
      are required for transcription of genes involved in hematopoiesis and
      development. MLL1 associates with a subcomplex containing WDR5, RbBP5, Ash2L, and
      DPY-30 (WRAD), which together form the MLL1 core complex that is required for
      sequential mono- and dimethylation of H3K4. We previously demonstrated that WDR5
      binds the conserved WDR5 interaction (Win) motif of MLL1 in vitro, an interaction
      that is required for the H3K4 dimethylation activity of the MLL1 core complex. In
      this investigation, we demonstrate that arginine 3765 of the MLL1 Win motif is
      required to co-immunoprecipitate WRAD from mammalian cells, suggesting that the
      WDR5-Win motif interaction is important for the assembly of the MLL1 core complex
      in vivo. We also demonstrate that peptides that mimic SET1 family Win motif
      sequences inhibit H3K4 dimethylation by the MLL1 core complex with varying
      degrees of efficiency. To understand the structural basis for these differences,
      we determined structures of WDR5 bound to six different naturally occurring Win
      motif sequences at resolutions ranging from 1.9 to 1.2 A. Our results reveal that
      binding energy differences result from interactions between non-conserved
      residues C-terminal to the Win motif and to a lesser extent from subtle variation
      of residues within the Win motif. These results highlight a new class of
      methylation inhibitors that may be useful for the treatment of MLL1-related
      malignancies.

PMID- 22665484
TI  - Differential expression and functionality of TRPA1 protein genetic variants in
      conditions of thermal stimulation.
AB  - The role of genetic modifications of the TRPA1 receptor has been well documented
      in inflammatory and neuropathic pain. We recently reported that the E179K variant
      of TRPA1 appears to be crucial for the generation of paradoxical heat sensation
      in pain patients. Here, we describe the consequences of the single amino acid
      exchange at position 179 in the ankyrin repeat 4 of human TRPA1. TRPA1 wild type
      Lys-179 protein expressed in HEK cells exhibited intact biochemical properties,
      inclusive trafficking into the plasma membrane, formation of large protein
      complexes, and the ability to be activated by cold. Additionally, a strong
      increase of Lys-179 protein expression was observed in cold (4  degrees C) and
      heat (49  degrees C)-treated cells. In contrast, HEK cells expressing the variant
      Lys-179 TRPA1 failed to get activated by cold possibly due to the loss of ability
      to interact with other proteins or other TRPA1 monomers during oligomerization.
      In conclusion, the detailed understanding of TRPA1 genetic variants might provide
      a fruitful strategy for future development of pain treatments.

PMID- 22665485
TI  - Misshapen-like kinase 1 (MINK1) is a novel component of striatin-interacting
      phosphatase and kinase (STRIPAK) and is required for the completion of
      cytokinesis.
AB  - Cytokinesis is initiated by constriction of the cleavage furrow and terminated by
      abscission of the intercellular bridge that connects two separating daughter
      cells. The complicated processes of cytokinesis are coordinated by
      phosphorylation and dephosphorylation mediated by protein kinases and
      phosphatases. Mammalian Misshapen-like kinase 1 (MINK1) is a member of the
      germinal center kinases and is known to regulate cytoskeletal organization and
      oncogene-induced cell senescence. To search for novel regulators of cytokinesis,
      we performed a screen using a library of siRNAs and found that MINK1 was
      essential for cytokinesis. Time-lapse analysis revealed that MINK1-depleted cells
      were able to initiate furrowing but that abscission was disrupted. STRN4
      (Zinedin) is a regulatory subunit of protein phosphatase 2A (PP2A) and was
      recently shown to be a component of a novel protein complex called striatin
      interacting phosphatase and kinase (STRIPAK). Mass spectrometry analysis showed
      that MINK1 was a component of STRIPAK and that MINK1 directly interacted with
      STRN4. Similar to MINK1 depletion, STRN4-knockdown induced multinucleated cells
      and inhibited the completion of abscission. In addition, STRN4 reduced MINK1
      activity in the presence of catalytic and structural subunits of PP2A. Our study
      identifies a novel regulatory network of protein kinases and phosphatases that
      regulate the completion of abscission.

PMID- 22665486
TI  - The RNase III enzyme DROSHA is essential for microRNA production and
      spermatogenesis.
AB  - DROSHA is a nuclear RNase III enzyme responsible for cleaving primary microRNAs
      (miRNAs) into precursor miRNAs and thus is essential for the biogenesis of
      canonical miRNAs. DICER is a cytoplasmic RNase III enzyme that not only cleaves
      precursor miRNAs to produce mature miRNAs but also dissects naturally
      formed/synthetic double-stranded RNAs to generate small interfering RNAs
      (siRNAs). To investigate the role of canonical miRNA and/or endogenous siRNA
      production in spermatogenesis, we generated Drosha or Dicer conditional knock-out
      (cKO) mouse lines by inactivating Drosha or Dicer exclusively in spermatogenic
      cells in postnatal testes using the Cre-loxp strategy. Both Drosha and Dicer cKO
      males were infertile due to disrupted spermatogenesis characterized by depletion
      of spermatocytes and spermatids leading to oligoteratozoospermia or azoospermia.
      The developmental course of spermatogenic disruptions was similar at
      morphological levels between Drosha and Dicer cKO males, but Drosha cKO testes
      appeared to be more severe in spermatogenic disruptions than Dicer cKO testes.
      Microarray analyses revealed transcriptomic differences between Drosha- and Dicer
      null pachytene spermatocytes or round spermatids. Although levels of sex-linked
      mRNAs were mildly elevated, meiotic sex chromosome inactivation appeared to have
      occurred normally. Our data demonstrate that unlike DICER, which is required for
      the biogenesis of several small RNA species, DROSHA is essential mainly for the
      canonical miRNA production, and DROSHA-mediated miRNA production is essential for
      normal spermatogenesis and male fertility.

PMID- 22665487
TI  - Molecular characteristics of Clostridium perfringens TpeL toxin and consequences
      of mono-O-GlcNAcylation of Ras in living cells.
AB  - TpeL is a member of the family of clostridial glucosylating toxins produced by
      Clostridium perfringens type A, B, and C strains. In contrast to other members of
      this toxin family, it lacks a C-terminal polypeptide repeat domain, which is
      suggested to be involved in target cell binding. It was shown that the
      glucosyltransferase domain of TpeL modifies Ras in vitro by mono-O-glucosylation
      or mono-O-GlcNAcylation (Nagahama, M., Ohkubo, A., Oda, M., Kobayashi, K.,
      Amimoto, K., Miyamoto, K., and Sakurai, J. (2011) Infect. Immun. 79, 905-910).
      Here we show that TpeL preferably utilizes UDP-N-acetylglucosamine (UDP-GlcNAc)
      as a sugar donor. Change of alanine 383 of TpeL to isoleucine turns the sugar
      donor preference from UDP-GlcNAc to UDP-glucose. In contrast to previous studies,
      we show that Rac is a poor substrate in vitro and in vivo and requires 1-2
      magnitudes higher toxin concentrations for modification by TpeL. The toxin is
      autoproteolytically processed in the presence of inositol hexakisphosphate
      (InsP(6)) by an intrinsic cysteine protease domain, located next to the
      glucosyltransferase domain. A C-terminally extended TpeL full-length variant
      (TpeL1-1779) induces apoptosis in HeLa cells (most likely by mono-O-GlcNAcylation
      of Ras), and inhibits Ras signaling including Ras-Raf interaction and ERK
      activation. In addition, TpeL blocks Ras signaling in rat pheochromocytoma PC12
      cells. TpeL is a glucosylating toxin, which modifies Ras and induces apoptosis in
      target cells without having a typical C-terminal polypeptide repeat domain.

PMID- 22665488
TI  - The protein Zfand5 binds and stabilizes mRNAs with AU-rich elements in their 3'
      untranslated regions.
AB  - AU-rich elements (AREs) in the 3'-UTR of unstable transcripts play a vital role
      in the regulation of many inflammatory mediators. To identify novel ARE-dependent
      gene regulators, we screened a human leukocyte cDNA library for candidates that
      enhanced the activity of a luciferase reporter bearing the ARE sequence from TNF
      (ARE(TNF)). Among 171 hits, we focused on Zfand5 (zinc finger, AN1-type domain
      5), a 23-kDa protein containing two zinc finger domains. Zfand5 expression was
      induced in macrophages in response to IFNgamma and Toll-like receptor ligands.
      Knockdown of Zfand5 in macrophages decreased expression of ARE class II
      transcripts TNF and COX2, whereas overexpression stabilized TNF mRNA by
      suppressing deadenylation. Zfand5 specifically bound to ARE(TNF) mRNA and
      competed with tristetraprolin, a protein known to bind and destabilize class II
      ARE-containing RNAs. Truncation studies indicated that both zinc fingers of
      Zfand5 contributed to its mRNA-stabilizing function. These findings add Zfand5 to
      the growing list of RNA-binding proteins and suggest that Zfand5 can enhance ARE
      containing mRNA stability by competing with tristetraprolin for mRNA binding.

PMID- 22665489
TI  - Transcriptional regulation of the protocadherin beta cluster during Her-2 protein
      induced mammary tumorigenesis results from altered N-glycan branching.
AB  - Changes in the levels of N-acetylglucosaminyltransferase V (GnT-V) can alter the
      function of several types of cell surface receptors and adhesion molecules by
      causing altered N-linked glycan branching. Using a her-2 mammary tumor mouse
      model, her-2 receptor signaling was down-regulated by GnT-V knock-out, resulting
      in a significant delay in the onset of her-2-induced mammary tumors. To identify
      the genes that contributed to this GnT-V regulation of early events in
      tumorigenesis, microarray analysis was performed using her-2 induced mammary
      tumors from wild-type and GnT-V-null mice. We found that 142 genes were
      aberrantly expressed (>2.0-fold) with 64 genes up-regulated and 78 genes down
      regulated after deletion of GnT-V. Among differentially expressed genes, the
      expression of a subgroup of the cadherin superfamily, the protocadherin beta
      (Pcdhbeta) cluster, was up-regulated in GnT-V-null tumors. Altered expression of
      the Pcdhbeta cluster in GnT-V-null tumors was not due to changes in promoter
      methylation; instead, impaired her-2-mediated signaling pathways were implicated
      at least in part resulting from reduced microRNA-21 expression. Overexpression of
      Pcdhbeta genes inhibited tumor cell growth, decreased the proportion of tumor
      initiating cells, and decreased tumor formation in vivo, demonstrating that
      expression of the Pcdhbeta gene cluster can serve as an inhibitor of the
      transformed phenotype. Our results suggest the up-regulation of the Pcdhbeta gene
      cluster as a mechanism for reduced her-2-mediated tumorigenesis resulting from
      GnT-V deletion.

PMID- 22665490
TI  - The cytosolic domain of protein-tyrosine kinase 7 (PTK7), generated from
      sequential cleavage by a disintegrin and metalloprotease 17 (ADAM17) and gamma
      secretase, enhances cell proliferation and migration in colon cancer cells.
AB  - Protein-tyrosine kinase 7 (PTK7) is a member of the defective receptor protein
      tyrosine kinases and is known to function as a regulator of planar cell polarity
      during development. Its expression is up-regulated in some cancers including
      colon carcinomas. A 100-kDa fragment of PTK7 was detected in the culture media
      from colon cancer cells and HEK293 cells. The shed fragment was named sPTK7-Ig1-7
      because its molecular mass was very similar to that of the entire extracellular
      domain of PTK7 that contains immunoglobulin-like loops 1 to 7 (Ig1-7). The
      shedding of sPTK7-Ig1-7 was enhanced by treatment with phorbol 12-myristate 13
      acetate. In addition to the sPTK7-Ig1-7 found in the culture medium, two C
      terminal fragments of PTK7 were detected in the cell lysates: PTK7-CTF1, which
      includes a transmembrane segment and a cytoplasmic domain, and PTK7-CTF2, which
      lacks most of the transmembrane segment from PTK7-CTF1. Analysis of PTK7
      processing in the presence of various protease inhibitors or after knockdown of
      potential proteases suggests that shedding of PTK7 into sPTK7-Ig1-7 and PTK7-CTF1
      is catalyzed by ADAM17, and further cleavage of PTK7-CTF1 into PTK7-CTF2 is
      mediated by the gamma-secretase complex. PTK7-CTF2 localizes to the nucleus and
      enhances proliferation, migration, and anchorage-independent colony formation.
      Our findings demonstrate a novel role for PTK7 in the tumorigenesis via
      generation of PTK7-CTF2 by sequential cleavage of ADAM17 and gamma-secretase.

PMID- 22665491
TI  - The second type VI secretion system of Pseudomonas aeruginosa strain PAO1 is
      regulated by quorum sensing and Fur and modulates internalization in epithelial
      cells.
AB  - The genome of Pseudomonas aeruginosa PAO1 contains three type VI secretion
      systems (T6SSs) called H1-, H2-, and H3-T6SS. The H1-T6SS secretes three
      identified toxins that target other bacteria, providing a fitness advantage for
      P. aeruginosa, and likely contributes to bacterial pathogenesis in chronic
      infections. However, no specific substrates or defined roles have been described
      for the two other systems. Here, we demonstrate that the expression of H2-T6SS
      genes of strain PAO1 is up-regulated during the transition from exponential to
      stationary phase growth and regulated by the Las and Rhl quorum sensing systems.
      In addition, we identify two putative Fur boxes in the promoter region and find
      that H2-T6SS transcription is negatively regulated by iron. We also show that the
      H2-T6SS system enhances bacterial uptake into HeLa cells (75% decrease in
      internalization with a H2-T6SS mutant) and into lung epithelial cells through a
      phosphatidylinositol 3-kinase-dependent pathway that induces Akt activation in
      the host cell (50% decrease in Akt phosphorylation). Finally, we show that H2
      T6SS plays a role in P. aeruginosa virulence in the worm model. Thus, in contrast
      to H1-T6SS, H2-T6SS modulates interaction with eukaryotic host cells. Together,
      T6SS can carry out different functions that may be important in establishing
      chronic P. aeruginosa infections in the human host.

PMID- 22665492
TI  - Mon1a protein acts in trafficking through the secretory apparatus.
AB  - Mon1a was originally identified as a modifier gene of vesicular traffic, as a
      mutant Mon1a allele resulted in increased localization of cell surface proteins,
      whereas reduced levels of Mon1a showed decreased secretory activity. Here we show
      that Mon1a affects different steps in the secretory pathway including endoplasmic
      reticulum-to-Golgi traffic. siRNA-dependent reduction of Mon1a levels resulted in
      a delay in the reformation of the Golgi apparatus after Brefeldin A treatment.
      Endoglycosidase H treatment of ts045VSVG-GFP confirmed that knockdown of Mon1a
      delayed endoplasmic reticulum-to-Golgi trafficking. Reductions in Mon1a also
      resulted in delayed trafficking from Golgi to the plasma membrane.
      Immunoprecipitation and mass spectrometry analysis showed that Mon1a associates
      with dynein intermediate chain. Reductions in Mon1a or dynein altered steady
      state Golgi morphology. Reductions in Mon1a delayed formation of ERGIC-53
      positive vesicles, whereas reductions in dynein did not affect vesicle formation.
      These data provide strong evidence for a role for Mon1a in anterograde
      trafficking through the secretory apparatus.

PMID- 22665493
TI  - RpaB, another response regulator operating circadian clock-dependent
      transcriptional regulation in Synechococcus elongatus PCC 7942.
AB  - The circadian clock of cyanobacteria is composed of KaiA, KaiB, and KaiC
      proteins, and the SasA-RpaA two-component system has been implicated in the
      regulation of one of the output pathways of the clock. In this study, we show
      that another response regulator that is essential for viability, the RpaA
      paralog, RpaB, plays a central role in the transcriptional oscillation of clock
      regulated genes. In vivo and in vitro analyses revealed that RpaB and not RpaA
      could specifically bind to the kaiBC promoter, possibly repressing transcription
      during subjective night. This suggested that binding may be terminated by RpaA to
      activate gene transcription during subjective day. Moreover, we found that rpoD6
      and sigF2, which encode group-2 and group-3 sigma factors for RNA polymerase,
      respectively, were also targets of the RpaAB system, suggesting that a specific
      group of sigma factors can propagate genome-wide transcriptional oscillation. Our
      findings thus reveal a novel mechanism for a circadian output pathway that is
      mediated by two paralogous response regulators.

PMID- 22665494
TI  - mrhl RNA, a long noncoding RNA, negatively regulates Wnt signaling through its
      protein partner Ddx5/p68 in mouse spermatogonial cells.
AB  - Meiotic recombination hot spot locus (mrhl) RNA is a nuclear enriched long
      noncoding RNA encoded in the mouse genome and expressed in testis, liver, spleen,
      and kidney. mrhl RNA silencing in Gc1-Spg cells, derived from mouse
      spermatogonial cells, resulted in perturbation of expression of genes belonging
      to cell adhesion, cell signaling and development, and differentiation, among
      which many were of the Wnt signaling pathway. A weighted gene coexpression
      network generated nine coexpression modules, which included TCF4, a key
      transcription factor involved in Wnt signaling. Activation of Wnt signaling upon
      mrhl RNA downregulation was demonstrated by beta-catenin nuclear localization,
      beta-catenin-TCF4 interaction, occupancy of beta-catenin at the promoters of Wnt
      target genes, and TOP/FOP-luciferase assay. Northwestern blot and RNA pulldown
      experiments identified Ddx5/p68 as one of the interacting proteins of mrhl RNA.
      Downregulation of mrhl RNA resulted in the cytoplasmic translocation of tyrosine
      phosphorylated p68. Concomitant downregulation of both mrhl RNA and p68 prevented
      the nuclear translocation of beta-catenin. mrhl RNA was downregulated on Wnt3a
      treatment in Gc1-Spg cells. This study shows that mrhl RNA plays a negative role
      in Wnt signaling in mouse spermatogonial cells through its interaction with p68.

PMID- 22665495
TI  - Ubiquitylation-dependent negative regulation of WASp is essential for actin
      cytoskeleton dynamics.
AB  - The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of actin dynamics
      during cell motility and adhesion, and mutations in its gene are responsible for
      Wiskott-Aldrich syndrome (WAS). Here, we demonstrate that WASp is ubiquitylated
      following T-cell antigen receptor (TCR) activation. WASp phosphorylation at
      tyrosine 291 results in recruitment of the E3 ligase Cbl-b, which, together with
      c-Cbl, carries out WASp ubiquitylation. Lysine residues 76 and 81, located at the
      WASp WH1 domain, which contains the vast majority of WASp gene mutations, serve
      as the ubiquitylation sites. Disruption of WASp ubiquitylation causes WASp
      accumulation and alters actin dynamics and the formation of actin-dependent
      structures. Our data suggest that regulated degradation of activated WASp might
      be an efficient strategy by which the duration and localization of actin
      rearrangement and the intensity of T-cell activation are controlled.

PMID- 22665496
TI  - Cross talk between signaling and vitamin A transport by the retinol-binding
      protein receptor STRA6.
AB  - The plasma membrane protein STRA6 transports vitamin A from its blood carrier
      retinol binding protein (RBP) into cells, and it also functions as a cytokine
      receptor which activates JAK/STAT signaling. We show here that, unlike other
      cytokine receptors, phosphorylation of STRA6 is not simply induced upon binding
      of its extracellular ligand. Instead, activation of the receptor is triggered by
      STRA6-mediated translocation of retinol from serum RBP to an intracellular
      acceptor, the retinol-binding protein CRBP-I. The observations also demonstrate
      that the movement of retinol from RBP to CRBP-I, and thus activation of STRA6, is
      critically linked to the intracellular metabolism of the vitamin. Furthermore,
      the data show that STRA6 phosphorylation is required for retinol uptake to
      proceed. Hence, the observations demonstrate that STRA6 orchestrates a
      multicomponent "machinery" that couples vitamin A homeostasis and metabolism to
      activation of a signaling cascade and that, in turn, STRA6 signaling regulates
      the cellular uptake of the vitamin. STRA6 appears to be a founding member of a
      new class of proteins that may be termed "cytokine signaling transporters."

PMID- 22665497
TI  - The stress response mediator ATF3 represses androgen signaling by binding the
      androgen receptor.
AB  - Activating transcription factor 3 (ATF3) is a common mediator of cellular stress
      response signaling and is often aberrantly expressed in prostate cancer. We
      report here that ATF3 can directly bind the androgen receptor (AR) and
      consequently repress AR-mediated gene expression. The ATF3-AR interaction
      requires the leucine zipper domain of ATF3 that independently binds the DNA
      binding and ligand-binding domains of AR, and the interaction prevents AR from
      binding to cis-acting elements required for expression of androgen-dependent
      genes while inhibiting the AR N- and C-terminal interaction. The functional
      consequences of the loss of ATF3 expression include increased transcription of
      androgen-dependent genes in prostate cancer cells that correlates with increased
      ability to grow in low-androgen-containing medium and increased proliferative
      activity of the prostate epithelium in ATF3 knockout mice that is associated with
      prostatic hyperplasia. Our results thus demonstrate that ATF3 is a novel
      repressor of androgen signaling that can inhibit AR functions, allowing prostate
      cells to restore homeostasis and maintain integrity in the face of a broad
      spectrum of intrinsic and environmental insults.

PMID- 22665499
TI  - Use of inertial sensors for ambulatory assessment of center-of-mass displacements
      during walking.
AB  - Current methods for center-of-mass (CoM) estimation are restricted to gait
      laboratories. The aim of this study was to estimate CoM displacement under
      ambulatory conditions with inertial sensors. A sacral inertial sensor (SIS
      method) was used to estimate the CoM displacement by double integration of the
      acceleration. Overestimation of the displacement caused by pelvic rotations was
      compensated (CSIS method). The CoM displacement estimations using the (C)SIS
      method were compared to the conventional methods of the segmental analysis (SA)
      method and the sacral marker (SM) method by the intraclass correlations and the
      root-mean-square (RMS) differences between the CoM curves. Accurate ambulatory
      measurement of the CoM displacement using inertial sensors was possible.
      Estimations of the sacrum position using the SIS method and the SM method were
      similar with mean (SD) RMS differences of 3.23 (0.87), 2.96 (0.42), and 3.22
      (0.78) mm for, respectively, the x-, y- and z-directions. The CoM estimation of
      the SIS method has RMS differences of 5.67 (1.20), 7.16 (3.28), and 3.49 (1.29)
      mm compared the SA method. The CSIS method shows a clear improvement in these
      estimations of the CoM with RMS differences of 5.52 (1.29), 4.44 (1.89), and 3.17
      (1.41) mm and is generally applicable for healthy subjects.

PMID- 22665500
TI  - Phase synchronization analysis of EEG signals: an evaluation based on surrogate
      tests.
AB  - Phase synchronization (PS) analysis has been demonstrated to be a useful method
      to infer functional connectivity with multichannel neural signals, e.g.,
      electroencephalography (EEG). Methodological problems on quantifying functional
      connectivity with PS analysis have been investigated extensively, but some of
      them have not been fully solved yet. For example, how long a segment of EEG
      signal should be used in estimating PS index? Which methods are more suitable to
      infer the significant level of estimated PS index? To address these questions,
      this paper performs an intensive computation study on PS analysis based on
      surrogate tests with 1) artificial surrogate data generated by shuffling the rank
      order, the phase spectra, or the instantaneous frequency of original EEG signals,
      and 2) intersubject EEG pairs under the assumption that the EEG signals of
      different subjects are independent. Results show that 1) the phase-shuffled
      surrogate method is workable for significance test of estimated PS index and
      yields results similar to those by intersubject EEG surrogate test; 2) generally,
      a duration of EEG waves covering about 3 16 cycles is suitable for PS analysis;
      and 3) the PS index based on mean phase coherence is more suitable for PS
      analysis of EEG signals recorded at relatively low sampling rate.

PMID- 22665498
TI  - The Abl and Arg kinases mediate distinct modes of phagocytosis and are required
      for maximal Leishmania infection.
AB  - Leishmania, an obligate intracellular parasite, binds several receptors to
      trigger engulfment by phagocytes, leading to cutaneous or visceral disease. These
      receptors include complement receptor 3 (CR3), used by promastigotes, and the Fc
      receptor (FcR), used by amastigotes. The mechanisms mediating uptake are not well
      understood. Here we show that Abl family kinases mediate both phagocytosis and
      the uptake of Leishmania amazonensis by macrophages (Ms). Imatinib, an Abl/Arg
      kinase inhibitor, decreases opsonized polystyrene bead phagocytosis and
      Leishmania uptake. Interestingly, phagocytosis of IgG-coated beads is decreased
      in Arg-deficient Ms, while that of C3bi-coated beads is unaffected. Conversely,
      uptake of C3bi-coated beads is decreased in Abl-deficient Ms, but that of IgG
      coated beads is unaffected. Consistent with these results, Abl-deficient Ms are
      inefficient at C3bi-opsonized promastigote uptake, and Arg-deficient Ms are
      defective in IgG1-opsonized amastigote uptake. Finally, genetic loss of Abl or
      Arg reduces infection severity in murine cutaneous leishmaniasis, and imatinib
      treatment results in smaller lesions with fewer parasites than in controls. Our
      studies are the first to demonstrate that efficient phagocytosis and maximal
      Leishmania infection require Abl family kinases. These results highlight Abl
      family kinase-mediated signaling pathways as potential therapeutic targets for
      leishmaniasis.

PMID- 22665501
TI  - Gaze estimation interpolation methods based on binocular data.
AB  - Video oculography (VOG) is one of the most commonly used techniques for gaze
      tracking because it enables nonintrusive eye detection and tracking. Improving
      the eye tracking's accuracy and tolerance to user head movements is a common task
      in the field of gaze tracking; thus, a thorough study of how binocular
      information can improve a gaze tracking system's accuracy and tolerance to user
      head movements has been carried out. The analysis is focused on interpolation
      based methods and systems with one and two infrared lights. New mapping features
      are proposed based on the commonly used pupil-glint vector using different
      distances as the normalization factor. For this study, an experimental procedure
      with six users based on a real VOG gaze tracking system was performed, and the
      results were contrasted with an eye simulator. Important conclusions have been
      obtained in terms of configuration, equation, and mapping features, such as the
      outperformance of the interglint distance as the normalization factor.
      Furthermore, the binocular gaze tracking system was found to have a similar or
      improved level of accuracy compared to that of the monocular gaze tracking
      system.

PMID- 22665502
TI  - Points of interest and visual dictionaries for automatic retinal lesion
      detection.
AB  - In this paper, we present an algorithm to detect the presence of diabetic
      retinopathy (DR)-related lesions from fundus images based on a common analytical
      approach that is capable of identifying both red and bright lesions without
      requiring specific pre- or postprocessing. Our solution constructs a visual word
      dictionary representing points of interest (PoIs) located within regions marked
      by specialists that contain lesions associated with DR and classifies the fundus
      images based on the presence or absence of these PoIs as normal or DR-related
      pathology. The novelty of our approach is in locating DR lesions in the optic
      fundus images using visual words that combines feature information contained
      within the images in a framework easily extendible to different types of retinal
      lesions or pathologies and builds a specific projection space for each class of
      interest (e.g., white lesions such as exudates or normal regions) instead of a
      common dictionary for all classes. The visual words dictionary was applied to
      classifying bright and red lesions with classical cross validation and cross
      dataset validation to indicate the robustness of this approach. We obtained an
      area under the curve (AUC) of 95.3% for white lesion detection and an AUC of
      93.3% for red lesion detection using fivefold cross validation and our own data
      consisting of 687 images of normal retinae, 245 images with bright lesions, 191
      with red lesions, and 109 with signs of both bright and red lesions. For cross
      dataset analysis, the visual dictionary also achieves compelling results using
      our images as the training set and the RetiDB and Messidor images as test sets.
      In this case, the image classification resulted in an AUC of 88.1% when
      classifying the RetiDB dataset and in an AUC of 89.3% when classifying the
      Messidor dataset, both cases for bright lesion detection. The results indicate
      the potential for training with different acquisition images under different
      setup conditions with a high accuracy of referral based on the presence of either
      red or bright lesions or both. The robustness of the visual dictionary against
      image quality (blurring), resolution, and retinal background, makes it a strong
      candidate for DR screening of large, diverse communities with varying cameras and
      settings and levels of expertise for image capture.

PMID- 22665503
TI  - Generalized EM-type reconstruction algorithms for emission tomography.
AB  - We provide a general form for many reconstruction estimators of emission
      tomography. These estimators include Shepp and Vardi's maximum likelihood (ML)
      estimator, the quadratic weighted least squares (WLS) estimator, Anderson's WLS
      estimator, and Liu and Wang's multi-objective estimator, and others. We derive a
      generic update rule by constructing a surrogate function. This work is inspired
      by the ML-EM (EM, expectation maximization), where the latter naturally arises as
      a special case. A regularization with a specific form can also be incorporated by
      De Pierro's trick. We provide a general and quite different convergence proof
      compared with the proofs of the ML-EM and De Pierro. Theoretical analysis shows
      that the proposed algorithm monotonically decreases the cost function and
      automatically meets nonnegativity constraints. We have introduced a mechanism to
      provide monotonic, self-constraining, and convergent algorithms, from which some
      interesting existing and new algorithms can be derived. Simulation results
      illustrate the behavior of these algorithms in term of image quality and
      resolution-noise tradeoff.

PMID- 22665504
TI  - Linear and nonlinear elastic modulus imaging: an application to breast cancer
      diagnosis.
AB  - We reconstruct the in vivo spatial distribution of linear and nonlinear elastic
      parameters in ten patients with benign (five) and malignant (five) tumors. The
      mechanical behavior of breast tissue is represented by a modified Veronda
      Westmann model with one linear and one nonlinear elastic parameter. The spatial
      distribution of these elastic parameters is determined by solving an inverse
      problem within the region of interest (ROI). This inverse problem solution
      requires the knowledge of the displacement fields at small and large strains. The
      displacement fields are measured using a free-hand ultrasound strain imaging
      technique wherein, a linear array ultrasound transducer is positioned on the
      breast and radio frequency echo signals are recorded within the ROI while the
      tissue is slowly deformed with the transducer. Incremental displacement fields
      are determined from successive radio-frequency frames by employing cross
      correlation techniques. The rectangular regions of interest were subjectively
      selected to obtain low noise displacement estimates and therefore were variables
      that ranged from 346 to 849.6 mm2 . It is observed that malignant tumors stiffen
      at a faster rate than benign tumors and based on this criterion nine out of ten
      tumors were correctly classified as being either benign or malignant.

PMID- 22665505
TI  - Multifeature landmark-free active appearance models: application to prostate MRI
      segmentation.
AB  - Active shape models (ASMs) and active appearance models (AAMs) are popular
      approaches for medical image segmentation that use shape information to drive the
      segmentation process. Both approaches rely on image derived landmarks (specified
      either manually or automatically) to define the object's shape, which require
      accurate triangulation and alignment. An alternative approach to modeling shape
      is the levelset representation, defined as a set of signed distances to the
      object's surface. In addition, using multiple image derived attributes (IDAs)
      such as gradient information has previously shown to offer improved segmentation
      results when applied to ASMs, yet little work has been done exploring IDAs in the
      context of AAMs. In this work, we present a novel AAM methodology that utilizes
      the levelset implementation to overcome the issues relating to specifying
      landmarks, and locates the object of interest in a new image using a registration
      based scheme. Additionally, the framework allows for incorporation of multiple
      IDAs. Our multifeature landmark-free AAM (MFLAAM) utilizes an efficient,
      intuitive, and accurate algorithm for identifying those IDAs that will offer the
      most accurate segmentations. In this paper, we evaluate our MFLAAM scheme for the
      problem of prostate segmentation from T2-w MRI volumes. On a cohort of 108
      studies, the levelset MFLAAM yielded a mean Dice accuracy of 88% +/- 5%, and a
      mean surface error of 1.5 mm +/-.8 mm with a segmentation time of 150/s per
      volume. In comparison, a state of the art AAM yielded mean Dice and surface error
      values of 86% +/- 9% and 1.6 mm +/- 1.0 mm, respectively. The differences with
      respect to our levelset-based MFLAAM model are statistically significant . In
      addition, our results were in most cases superior to several recent state of the
      art prostate MRI segmentation methods.

PMID- 22665506
TI  - Nonsupervised ranking of different segmentation approaches: application to the
      estimation of the left ventricular ejection fraction from cardiac cine MRI
      sequences.
AB  - A statistical methodology is proposed to rank several estimation methods of a
      relevant clinical parameter when no gold standard is available. Based on a
      regression without truth method, the proposed approach was applied to rank eight
      methods without using any a priori information regarding the reliability of each
      method and its degree of automation. It was only based on a prior concerning the
      statistical distribution of the parameter of interest in the database. The
      ranking of the methods relies on figures of merit derived from the regression and
      computed using a bootstrap process. The methodology was applied to the estimation
      of the left ventricular ejection fraction derived from cardiac magnetic resonance
      images segmented using eight approaches with different degrees of automation:
      three segmentations were entirely manually performed and the others were
      variously automated. The ranking of methods was consistent with the expected
      performance of the estimation methods: the most accurate estimates of the
      ejection fraction were obtained using manual segmentations. The robustness of the
      ranking was demonstrated when at least three methods were compared. These results
      suggest that the proposed statistical approach might be helpful to assess the
      performance of estimation methods on clinical data for which no gold standard is
      available.

PMID- 22665507
TI  - Personalization of atrial anatomy and electrophysiology as a basis for clinical
      modeling of radio-frequency ablation of atrial fibrillation.
AB  - Multiscale cardiac modeling has made great advances over the last decade. Highly
      detailed atrial models were created and used for the investigation of initiation
      and perpetuation of atrial fibrillation. The next challenge is the use of
      personalized atrial models in clinical practice. In this study, a framework of
      simple and robust tools is presented, which enables the generation and validation
      of patient-specific anatomical and electrophysiological atrial models.
      Introduction of rule-based atrial fiber orientation produced a realistic
      excitation sequence and a better correlation to the measured electrocardiograms.
      Personalization of the global conduction velocity lead to a precise match of the
      measured P-wave duration. The use of a virtual cohort of nine patient and
      volunteer models averaged out possible model-specific errors. Intra-atrial
      excitation conduction was personalized manually from left atrial local activation
      time maps. Inclusion of LE-MRI data into the simulations revealed possible gaps
      in ablation lesions. A fast marching level set approach to compute atrial
      depolarization was extended to incorporate anisotropy and conduction velocity
      heterogeneities and reproduced the monodomain solution. The presented chain of
      tools is an important step towards the use of atrial models for the patient
      specific AF diagnosis and ablation therapy planing.

PMID- 22665508
TI  - Optimization of neural networks using variable structure systems.
AB  - This paper proposes a new mixed training algorithm consisting of error
      backpropagation (EBP) and variable structure systems (VSSs) to optimize parameter
      updating of neural networks. For the optimization of the number of neurons in the
      hidden layer, a new term based on the output of the hidden layer is added to the
      cost function as a penalty term to make optimal use of hidden units related to
      weights corresponding to each unit in the hidden layer. VSS is used to control
      the dynamic model of the training process, whereas EBP attempts to minimize the
      cost function. In addition to the analysis of the imposed dynamics of the EBP
      technique, the global stability of the mixed training methodology and constraints
      on the design parameters are considered. The advantages of the proposed technique
      are guaranteed convergence, improved robustness, and lower sensitivity to initial
      weights of the neural network.

PMID- 22665509
TI  - Gait recognition across various walking speeds using higher order shape
      configuration based on a differential composition model.
AB  - Gait has been known as an effective biometric feature to identify a person at a
      distance. However, variation of walking speeds may lead to significant changes to
      human walking patterns. It causes many difficulties for gait recognition. A
      comprehensive analysis has been carried out in this paper to identify such
      effects. Based on the analysis, Procrustes shape analysis is adopted for gait
      signature description and relevant similarity measurement. To tackle the
      challenges raised by speed change, this paper proposes a higher order shape
      configuration for gait shape description, which deliberately conserves
      discriminative information in the gait signatures and is still able to tolerate
      the varying walking speed. Instead of simply measuring the similarity between two
      gaits by treating them as two unified objects, a differential composition model
      (DCM) is constructed. The DCM differentiates the different effects caused by
      walking speed changes on various human body parts. In the meantime, it also
      balances well the different discriminabilities of each body part on the overall
      gait similarity measurements. In this model, the Fisher discriminant ratio is
      adopted to calculate weights for each body part. Comprehensive experiments based
      on widely adopted gait databases demonstrate that our proposed method is
      efficient for cross-speed gait recognition and outperforms other state-of-the-art
      methods.

PMID- 22665510
TI  - Passivity and Passification for a Class of Uncertain Switched Stochastic Time
      Delay Systems.
AB  - This paper is concerned with the problems of passivity and passification for a
      class of uncertain switched systems subject to stochastic disturbance and time
      varying delay. The passivity property is adopted to analyze the influence of the
      external disturbance on such systems to achieve prescribed attenuation levels.
      Based on average dwell time approach, free-weighting matrix method, and Jensen's
      integral inequality, delay-dependent sufficient conditions are obtained in terms
      of linear matrix inequalities, which ensure the uncertain switched stochastic
      time-delay system to be robustly mean-square exponentially stable and
      stochastically passive. Then, the switched passive controllers are synthesized by
      linearization techniques. Finally, two numerical examples are given to illustrate
      the effectiveness of the proposed methods. 

PMID- 22665511
TI  - A One-Layer Recurrent Neural Network for Real-Time Portfolio Optimization With
      Probability Criterion.
AB  - This paper presents a decision-making model described by a recurrent neural
      network for dynamic portfolio optimization. The portfolio-optimization problem is
      first converted into a constrained fractional programming problem. Since the
      objective function in the programming problem is not convex, the traditional
      optimization techniques are no longer applicable for solving this problem.
      Fortunately, the objective function in the fractional programming is pseudoconvex
      on the feasible region. It leads to a one-layer recurrent neural network modeled
      by means of a discontinuous dynamic system. To ensure the optimal solutions for
      portfolio optimization, the convergence of the proposed neural network is
      analyzed and proved. In fact, the neural network guarantees to get the optimal
      solutions for portfolio-investment advice if some mild conditions are satisfied.
      A numerical example with simulation results substantiates the effectiveness and
      illustrates the characteristics of the proposed neural network. 

PMID- 22665512
TI  - Prostate cancer localization using multiparametric MRI based on semi-supervised
      techniques with automated seed initialization.
AB  - In this paper, we propose a novel and efficient semisupervised technique for
      automated prostate cancer localization using multiparametric magnetic resonance
      imaging (MRI). This method can be used in guiding biopsy, surgery, and therapy.
      We systematically present a new segmentation technique by developing a
      multiparametric graph based random walker (RW) algorithm with automated seed
      initialization to perform prostate cancer segmentation using multiparametric MRI.
      RW algorithm has proved to be accurate and fast in segmentation applications;
      however it requires a set of (user provided) seed points in order to perform
      segmentation. In this study, we first developed a novel RW method, which can be
      used with multiparametric MR images and then devised alternative methods that can
      determine seed points in an automated manner using discriminative classifiers
      such as support vector machines (SVM). Proposed RW method with automated seed
      initialization is able to produce improved segmentation results by assigning more
      weights to the images with more discriminative power.We applied the proposed
      method to a multiparametric dataset obtained from biopsy confirmed prostate
      cancer patients. Proposed method produces a sensitivity/ specificity rate of 0.76
      and 0.86, respectively. Both visual, quantitative as well as statistical results
      are presented to show the significant performance improvements. Fisher sign test
      is used to demonstrate the statistical significance of our results by achieving p
      values less than 0.05. This method outperforms available RW and SVM based methods
      by achieving a high specificity rate while not reducing sensitivity. 

PMID- 22665513
TI  - Patient-specific prediction of coronary plaque growth from CTA angiography: a
      multiscale model for plaque formation and progression.
AB  - Computational fluid dynamics methods based on in vivo 3-D vessel reconstructions
      have recently been identified the influence of wall shear stress on endothelial
      cells as well as on vascular smooth muscle cells, resulting in different events
      such as flow mediated vasodilatation, atherosclerosis, and vascular remodeling.
      Development of image-based modeling technologies for simulating patient-specific
      local blood flows is introducing a novel approach to risk prediction for coronary
      plaque growth and progression. In this study, we developed 3-D model of plaque
      formation and progression that was tested in a set of patients who underwent
      coronary computed tomography angiography (CTA) for anginal symptoms. The 3-D
      blood flow is described by the Navier-Stokes equations, together with the
      continuity equation. Mass transfer within the blood lumen and through the
      arterial wall is coupled with the blood flow and is modeled by a convection
      diffusion equation. The low density lipoprotein (LDL) transports in lumen of the
      vessel and through the vessel tissue (which has a mass consumption term) are
      coupled by Kedem-Katchalsky equations. The inflammatory process is modeled using
      three additional reaction-diffusion partial differential equations. A full 3-D
      model was created. It includes blood flow and LDL concentration, as well as
      plaque formation and progression. Furthermore, features potentially affecting
      plaque growth, such as patient risk score, circulating biomarkers, localization
      and composition of the initial plaque, and coronary vasodilating capability were
      also investigated. The proof of concept of the model effectiveness was assessed
      by repetition of CTA, six months after.

PMID- 22665514
TI  - Control of upper limb prostheses: terminology and proportional myoelectric
      control-a review.
AB  - The recent introduction of novel multifunction hands as well as new control
      paradigms increase the demand for advanced prosthetic control systems. In this
      context, an unambiguous terminology and a good understanding of the nature of the
      control problem is important for efficient research and communication concerning
      the subject. Thus, one purpose of this paper is to suggest an unambiguous
      taxonomy, applicable to control systems for upper limb prostheses and also to
      prostheses in general. A functionally partitioned model of the prosthesis control
      problem is also presented along with the taxonomy. In the second half of the
      paper, the suggested taxonomy has been exploited in a comprehensive literature
      review on proportional myoelectric control of upper limb prostheses. The review
      revealed that the methods for system training have not matured at the same pace
      as the novel multifunction prostheses and more advanced intent interpretation
      methods. Few publications exist regarding the choice of training method and the
      composition of the training data set. In this context, the notion of outcome
      measures is essential. By definition, system training involves optimization, and
      the quality of the results depends heavily on the choice of appropriate
      optimization criteria. In order to further promote the development of
      proportional myoelectric control, these topics need to be addressed.

PMID- 22665515
TI  - [Safety and efficacy of bevacizumab combined with taxanes in the first-line
      treatment of metastatic breast cancer: ATHENA study-France].
AB  - The efficacy of the combination bevacizumab-chemotherapy in the first-line
      treatment of metastatic breast cancer (mBC) was demonstrated in several
      randomized clinical trials. However, limited safety data is available in daily
      medical practice. ATHENA is an international phase-IIIb study conducted in 2,251
      patients with locally advanced or mBC, treated in first-line with bevacizumab
      combined with taxanes-based chemotherapy. The primary objective is safety
      assessment. In France, 365 patients were included. Their median age was 56 years
      (24-93 years) and ECOG performance status was 0 or 1 in 93.9% of patients.
      Bevacizumab was essentially combined with a taxanes monotherapy: docetaxel
      (37.3%) or paclitaxel (28.8%) or taxanes-based combination therapy (9.4%). The
      most frequent grade superior or equal to 3 adverse event (AE) was neutropenia
      (34.5%). Grade superior or equal to 3 AEs of special interest related to
      bevacizumab were arterial and venous thromboembolism (5.1%), high blood pressure
      (4.2%), proteinuria (2.3%) and hemorrhage (2%). Median time to progression was
      9.5 months (95% CI: 8.8-10.4). The safety profile and the efficacy of the
      combination bevacizumab-taxanes in a population more representative of daily
      oncology practice in France are comparable to those reported in clinical trials
      in mBC.

PMID- 22665517
TI  - Genetic association of CCR5 promoter single nucleotide polymorphism in
      seronegative and seropositive rheumatoid arthritis.
AB  - The aim of this study was to investigate the possible role of the CCR5 59029 A->G
      promoter point mutation polymorphism in determining the susceptibility to
      rheumatoid factor-positive and rheumatoid factor-negative rheumatoid arthritis.
      This polymorphism was assessed in 85 seropositive and 39 seronegative rheumatoid
      arthritis patients and in 126 healthy individuals of the same geographic and
      ethnic origin. We found an increase in the genetic frequency of the A allele in
      the 59029 A->G promoter region of the CCR5 receptor in patients with rheumatoid
      arthritis compared with healthy controls (p = 0.01; OR = 1.5, 95% CI (1.0-2.2).
      Likewise, the homozygous state for the A allele was found to be more frequent in
      rheumatoid arthritis patients, again when compared with healthy controls (p =
      0.03; OR = 1.8, 95% CI 1.0-3.0). The increased frequency of the A allele was more
      evident in the more benign, seronegative rheumatoid arthritis group when compared
      with controls (p = 0.003; OR 2.4 95% CI 1.3-4.4), and when combining the A
      homozygous and the AG heterozygous patients compared with healthy subjects. These
      results suggest that this CCR5 promoter polymorphism seems to play an important
      role in determining different clinical courses in both forms of rheumatoid
      arthritis.

PMID- 22665516
TI  - An interaction map of endoplasmic reticulum chaperones and foldases.
AB  - Chaperones and foldases in the endoplasmic reticulum (ER) ensure correct protein
      folding. Extensive protein-protein interaction maps have defined the organization
      and function of many cellular complexes, but ER complexes are under-represented.
      Consequently, chaperone and foldase networks in the ER are largely
      uncharacterized. Using complementary ER-specific methods, we have mapped
      interactions between ER-lumenal chaperones and foldases and describe their
      organization in multiprotein complexes. We identify new functional chaperone
      modules, including interactions between protein-disulfide isomerases and peptidyl
      prolyl cis-trans-isomerases. We have examined in detail a novel ERp72-cyclophilin
      B complex that enhances the rate of folding of immunoglobulin G. Deletion
      analysis and NMR reveal a conserved surface of cyclophilin B that interacts with
      polyacidic stretches of ERp72 and GRp94. Mutagenesis within this highly charged
      surface region abrogates interactions with its chaperone partners and reveals a
      new mechanism of ER protein-protein interaction. This ability of cyclophilin B to
      interact with different partners using the same molecular surface suggests that
      ER-chaperone/foldase partnerships may switch depending on the needs of different
      substrates, illustrating the flexibility of multichaperone complexes of the ER
      folding machinery.

PMID- 22665518
TI  - Smooth muscle-endothelial cell communication activates Reelin signaling and
      regulates lymphatic vessel formation.
AB  - Active lymph transport relies on smooth muscle cell (SMC) contractions around
      collecting lymphatic vessels, yet regulation of lymphatic vessel wall assembly
      and lymphatic pumping are poorly understood. Here, we identify Reelin, an
      extracellular matrix glycoprotein previously implicated in central nervous system
      development, as an important regulator of lymphatic vascular development. Reelin
      deficient mice showed abnormal collecting lymphatic vessels, characterized by a
      reduced number of SMCs, abnormal expression of lymphatic capillary marker
      lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and impaired
      function. Furthermore, we show that SMC recruitment to lymphatic vessels
      stimulated release and proteolytic processing of endothelium-derived Reelin.
      Lymphatic endothelial cells in turn responded to Reelin by up-regulating monocyte
      chemotactic protein 1 (MCP1) expression, which suggests an autocrine mechanism
      for Reelin-mediated control of endothelial factor expression upstream of SMC
      recruitment. These results uncover a mechanism by which Reelin signaling is
      activated by communication between the two cell types of the collecting lymphatic
      vessels--smooth muscle and endothelial cells--and highlight a hitherto
      unrecognized and important function for SMCs in lymphatic vessel morphogenesis
      and function.

PMID- 22665519
TI  - F-actin polymerization and retrograde flow drive sustained PLCgamma1 signaling
      during T cell activation.
AB  - Activation of T cells by antigen-presenting cells involves assembly of signaling
      molecules into dynamic microclusters (MCs) within a specialized membrane domain
      termed the immunological synapse (IS). Actin and myosin IIA localize to the IS,
      and depletion of F-actin abrogates MC movement and T cell activation. However,
      the mechanisms that coordinate actomyosin dynamics and T cell receptor signaling
      are poorly understood. Using pharmacological inhibitors that perturb individual
      aspects of actomyosin dynamics without disassembling the network, we demonstrate
      that F-actin polymerization is the primary driver of actin retrograde flow,
      whereas myosin IIA promotes long-term integrity of the IS. Disruption of F-actin
      retrograde flow, but not myosin IIA contraction, arrested MC centralization and
      inhibited sustained Ca(2+) signaling at the level of endoplasmic reticulum store
      release. Furthermore, perturbation of retrograde flow inhibited PLCgamma1
      phosphorylation within MCs but left Zap70 activity intact. These studies
      highlight the importance of ongoing actin polymerization as a central driver of
      actomyosin retrograde flow, MC centralization, and sustained Ca(2+) signaling.

PMID- 22665520
TI  - Arginylation-dependent regulation of a proteolytic product of talin is essential
      for cell-cell adhesion.
AB  - Talin is a large scaffolding molecule that plays a major role in integrin
      dependent cell-matrix adhesion. A role for talin in cell-cell attachment through
      cadherin has never been demonstrated, however. Here, we identify a novel calpain
      dependent proteolytic cleavage of talin that results in the release of a 70-kD C
      terminal fragment, which serves as a substrate of posttranslational arginylation.
      The intracellular levels of this fragment closely correlated with the formation
      of cell-cell adhesions, and this fragment localized to cadherin-containing cell
      cell contacts. Moreover, reintroduction of this fragment rescued the cell-cell
      adhesion defects in arginyltransferase (Ate1) knockout cells, which normally have
      a very low level of this fragment. Arginylation of this fragment further enhanced
      its ability to rescue cell-cell adhesion formation. In addition, arginylation
      facilitated its turnover, suggesting a dual role of arginylation in its
      intracellular regulation. Thus, our work identifies a novel proteolytic product
      of talin that is regulated by arginylation and a new role of talin in cadherin
      dependent cell-cell adhesion.

PMID- 22665521
TI  - 2D protrusion but not motility predicts growth factor-induced cancer cell
      migration in 3D collagen.
AB  - Growth factor-induced migration is a critical step in the dissemination and
      metastasis of solid tumors. Although differences in properties characterizing
      cell migration on two-dimensional (2D) substrata versus within three-dimensional
      (3D) matrices have been noted for particular growth factor stimuli, the 2D
      approach remains in more common use as an efficient surrogate, especially for
      high-throughput experiments. We therefore were motivated to investigate which
      migration properties measured in various 2D assays might be reflective of 3D
      migratory behavioral responses. We used human triple-negative breast cancer lines
      stimulated by a panel of receptor tyrosine kinase ligands relevant to mammary
      carcinoma progression. Whereas 2D migration properties did not correlate well
      with 3D behavior across multiple growth factors, we found that increased membrane
      protrusion elicited by growth factor stimulation did relate robustly to enhanced
      3D migration properties of the MDA-MB-231 and MDA-MB-157 lines. Interestingly, we
      observed this to be a more reliable relationship than cognate receptor expression
      or activation levels across these and two additional mammary tumor lines.

PMID- 22665522
TI  - FGFR1 cleavage and nuclear translocation regulates breast cancer cell behavior.
AB  - FGF-10 and its receptors, FGFR1 and FGFR2, have been implicated in breast cancer
      susceptibility and progression, suggesting that fibroblast growth factor (FGF)
      signaling may be co-opted by breast cancer cells. We identify a novel pathway
      downstream of FGFR1 activation, whereby the receptor is cleaved and traffics to
      the nucleus, where it can regulate specific target genes. We confirm Granzyme B
      (GrB) as the protease responsible for cleavage and show that blocking GrB
      activity stopped FGFR1 trafficking to the nucleus and abrogates the promigratory
      effect of FGF stimulation. We confirm the in vivo relevance of our findings,
      showing that FGFR1 localized to the nucleus specifically in invading cells in
      both clinical material and a three-dimensional model of breast cancer. We
      identify target genes for FGFR1, which exert significant effects on cell
      migration and may represent an invasive signature. Our experiments identify a
      novel mechanism by which FGF signaling can regulate cancer cell behavior and
      provide a novel therapeutic target for treatment of invasive breast cancer.

PMID- 22665523
TI  - PRAK suppresses oncogenic ras-induced hematopoietic cancer development by
      antagonizing the JNK pathway.
AB  - The p38 mitogen-activated protein kinase (MAPK) pathway regulates multiple
      physiologic and pathologic processes, including cancer development. PRAK, a p38
      substrate protein kinase, has previously been implicated in the suppression of
      skin carcinogenesis. In the current study, we show that PRAK deletion accelerates
      hematopoietic cancer development in a mouse model harboring an oncogenic ras
      allele, EMU-N-Ras(G12D), specifically expressed in hematopoietic cells. Further
      investigation reveals that enhanced hematopoietic tumorigenesis by PRAK
      deficiency is associated with hyperactivation of the c-jun-NH(2)-kinase (JNK)
      pathway both in vivo and in primary hematopoietic cells isolated from spleens. In
      primary splenocytes, PRAK deficiency further enhanced oncogenic ras-induced cell
      proliferation and promoted ras-mediated colony formation on semisolid medium in a
      JNK-dependent manner. In addition, deletion of PRAK leads to abrogation of ras
      induced accumulation of senescence markers. These findings indicate that PRAK
      suppresses hematopoietic cancer formation in this mouse model by antagonizing
      oncogenic ras-induced activation of the JNK pathway. Our results suggest that
      PRAK may function as a tumor suppressor in multiple types of cancers.

PMID- 22665524
TI  - Sorafenib inhibits many kinase mutations associated with drug-resistant
      gastrointestinal stromal tumors.
AB  - Sorafenib has substantial clinical activity as third- or fourth-line treatment of
      imatinib- and sunitinib-resistant gastrointestinal stromal tumors (GIST). Because
      sorafenib targets both angiogenesis-related kinases (VEGFR) and the pathogenetic
      kinases found in GIST (KIT or PDGFRA), the molecular basis for sorafenib efficacy
      in this setting remains unknown. We sought to determine the spectrum of activity
      of sorafenib against different mutant kinases associated with drug-sensitive and
      drug-resistant GIST. We compared the activity of imatinib and sorafenib against
      transiently expressed mutant forms of KIT and PDGFRA, including various secondary
      mutations that have been identified in imatinib-resistant or sunitinib-resistant
      GISTs. We also examined these drugs against four GIST cell lines, three of which
      are imatinib resistant. In our in vitro studies, we determined that sorafenib
      inhibited imatinib-resistant mutations in exons encoding the ATP/drug-binding
      pocket and in exons encoding the activation loop, with the exception of
      substitutions at KIT codon D816 and PDGFRA codon 842. Notably our data indicate
      that sorafenib is more effective than imatinib or sunitinib for inhibiting the
      kinase activity of drug-resistant KIT mutants (as assessed by biochemical
      IC(50)). We hypothesize that a major determinant of the efficacy of sorafenib for
      treatment of advanced GIST is the activity of this agent against KIT or PDGFRA
      mutant kinases. These results have implications for the further development of
      treatments for drug-resistant GIST.

PMID- 22665526
TI  - Novel insights on TLX1 function in T-ALL pave the way towards differentiation
      therapy.

PMID- 22665525
TI  - Pharmacogenomic profiling and pathway analyses identify MAPK-dependent migration
      as an acute response to SN38 in p53 null and p53-mutant colorectal cancer cells.
AB  - The topoisomerase I inhibitor irinotecan is used to treat advanced colorectal
      cancer and has been shown to have p53-independent anticancer activity. The aim of
      this study was to identify the p53-independent signaling mechanisms activated by
      irinotecan. Transcriptional profiling of isogenic HCT116 p53 wild-type and p53
      null cells was carried out following treatment with the active metabolite of
      irinotecan, SN38. Unsupervised analysis methods showed that p53 status had a
      highly significant impact on gene expression changes in response to SN38. Pathway
      analysis indicated that pathways involved in cell motility [adherens junction,
      focal adhesion, mitogen-activated protein kinase (MAPK), and regulation of the
      actin cytoskeleton] were significantly activated in p53 null cells, but not p53
      wild-type cells, following SN38 treatment. In functional assays, SN38 treatment
      increased the migratory potential of p53 null and p53-mutant colorectal cancer
      cell lines, but not p53 wild-type lines. Moreover, p53 null SN38-resistant cells
      were found to migrate at a faster rate than parental drug-sensitive p53 null
      cells, whereas p53 wild-type SN38-resistant cells failed to migrate. Notably,
      cotreatment with inhibitors of the MAPK pathway inhibited the increased migration
      observed following SN38 treatment in p53 null and p53-mutant cells. Thus, in the
      absence of wild-type p53, SN38 promotes migration of colorectal cancer cells, and
      inhibiting MAPK blocks this potentially prometastatic adaptive response to this
      anticancer drug.

PMID- 22665527
TI  - New opportunities and new problems for acute myeloid leukemia treatment.

PMID- 22665528
TI  - Positron emission tomography/computed tomography surveillance in patients with
      lymphoma: a fox hunt?

PMID- 22665529
TI  - Optimizing investigator-led oncology research in Europe.

PMID- 22665530
TI  - Characterization of potential CD138 negative myeloma "stem cells".

PMID- 22665531
TI  - Early interim 2-(1)fluoro-2-deoxy-D-glucose positron emission tomography is
      prognostically superior to peripheral blood lymphocyte/monocyte ratio at
      diagnosis in classical Hodgkin's lymphoma.

PMID- 22665533
TI  - TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin
      in stage IV triple-negative breast cancer.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) is a targetable receptor
      frequently overexpressed in basal-like breast cancer, which comprises most triple
      negative breast cancers (TNBCs), the only subtype without established targeted
      therapy. PATIENTS AND METHODS: In this randomized phase II trial, patients with
      metastatic TNBC received anti-EGFR antibody cetuximab (400 mg/m(2) load then 250
      mg/m(2) per week intravenously [IV]) alone, with carboplatin (area under the
      curve of 2, once per week IV) added after progression or as concomitant therapy
      from the beginning. Response rate (RR) was the primary end point; others included
      time to progression (TTP), overall survival (OS), and toxicity. Embedded
      correlative studies included molecular subtyping on archival tissue. Fresh tumor
      tissue before and after 7 to 14 days of therapy was used for microarray analyses
      exploring EGFR pathway activity and inhibition. RESULTS: In 102 patients with
      TNBC, RRs were 6% (two of 31) to cetuximab and 16% (four of 25) to cetuximab plus
      carboplatin after progression. RR to those treated from the beginning with
      cetuximab plus carboplatin was 17% (12 of 71); 31% of patients responded or had
      prolonged disease stabilization. The cetuximab plus carboplatin regimen was well
      tolerated, but both TTP and OS were short at 2.1 months (95% CI, 1.8 to 5.5
      months) and 10.4 months (95% CI, 7.7 to 13.1 months), respectively. Of 73
      patients with archival tissue for analysis, 74% had basal-like molecular subtype.
      Sixteen patients had tumor biopsies before and 1 week after therapy; genomic
      patterns of the EGFR pathway showed activation in 13 and inhibition by therapy in
      five. CONCLUSION: Despite strong preclinical data, combination cetuximab plus
      carboplatin in metastatic TNBC produced responses in fewer than 20% of patients.
      EGFR pathway analysis showed that most TNBCs involved activation. However,
      cetuximab blocked expression of the EGFR pathway in only a minority, suggesting
      that most had alternate mechanisms for pathway activation.

PMID- 22665534
TI  - Randomized comparison of intensified six-drug versus standard three-drug
      chemotherapy for high-risk nonmetastatic rhabdomyosarcoma and other chemotherapy
      sensitive childhood soft tissue sarcomas: long-term results from the
      International Society of Pediatric Oncology MMT95 study.
AB  - PURPOSE: MMT95 was the fourth of a series of International Society of Pediatric
      Oncology (SIOP) collaborations for children with high-risk nonmetastatic soft
      tissue sarcoma (STS). The principal objective was to explore survival advantage
      for an intensified chemotherapy strategy in a randomized trial. PATIENTS AND
      METHODS: From July 1995 to June 2003, 457 previously untreated patients with
      incompletely resected embryonal rhabdomyosarcoma (RMS), undifferentiated sarcoma,
      and soft tissue primitive neuroectodermal tumor at all sites except
      paratesticular, vagina, and uterus, or with alveolar RMS were randomly assigned
      to receive either ifosfamide, vincristine, and dactinomycin (IVA) or a six-drug
      combination (IVA plus carboplatin, epirubicin, and etoposide) both delivered over
      27 weeks. Cumulative doses were as follows: ifosfamide 54 g/m(2) (both arms),
      epirubicin 450 mg/m(2), etoposide 1,350 mg/m(2) (six-drug regimen). Poor
      responders after three courses of IVA were to be switched to the other arm.
      Delivery of radiotherapy was determined according to site and/or response to
      chemotherapy with or without surgery. RESULTS: Overall survival (OS) for all
      patients was 81% (95% CI, 77% to 84%) at 3 years. No significant difference in
      outcome in either OS or event-free survival was noted between the two arms (3
      year OS: 82% [95% CI, 76% to 86%] for IVA and 80% [95% CI, 74% to 85%] for the
      six-drug arm). Toxicity was significantly greater (infection, myelosuppression,
      and mucositis) in the six-drug arm. Overall burden of local therapy was
      consistent with data from previous SIOP studies and showed no difference between
      the two chemotherapy regimens. CONCLUSION: Intensification of chemotherapy for
      nonmetastatic RMS and other chemotherapy-sensitive STS provides no survival
      advantage or reduction in the intensity of local therapy and adds toxicity.

PMID- 22665535
TI  - Randomized study of two chemotherapy regimens for treatment of low-grade glioma
      in young children: a report from the Children's Oncology Group.
AB  - PURPOSE Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in
      areas of the brain amenable to complete resection. However, LGGs located in areas
      where complete resection is not possible can threaten both function and life. The
      purpose of this study was to compare two chemotherapy regimens for LGGs in
      children younger than age 10 years for whom radiotherapy was felt by the
      practitioner to pose a high risk of neurodevelopmental injury.   PATIENTS AND
      METHODS Previously untreated children younger than age 10 years with progressive
      or residual LGGs were eligible. Children were randomly assigned to receive
      carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and
      vincristine (TPCV). Children with neurofibromatosis are reported separately. 
      Results Of 274 randomly assigned patients who met eligibility requirements, 137
      received CV and 137 received TPCV. The 5-year event-free survival (EFS) and
      overall survival (OS) rates for all eligible patients were 45% +/- 3.2% and 86%
      +/- 2.2%, respectively. The 5-year EFS rates were 39% +/- 4% for CV and 52% +/-
      5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007). On
      multivariate analysis, factors independently predictive of worse EFS and OS were
      younger age and tumor size greater than 3 cm(2). Tumor location in the thalamus
      was also associated with poor OS.   CONCLUSION The difference in EFS between the
      regimens did not reach significance on the basis of the stratified log-rank test.
      The 5-year EFS was higher for TPCV on the basis of the cure model analysis.
      Differences in toxicity may influence physician choice of regimens.

PMID- 22665536
TI  - Effect of adjuvant chemotherapy on survival of patients with stage III colon
      cancer diagnosed after age 75 years.
AB  - PURPOSE: Few patients 75 years of age and older participate in clinical trials,
      thus whether adjuvant chemotherapy for stage III colon cancer (CC) benefits this
      group is unknown. METHODS: A total of 5,489 patients >= 75 years of age with
      resected stage III CC, diagnosed between 2004 and 2007, were selected from four
      data sets containing demographic, stage, treatment, and survival information.
      These data sets included SEER-Medicare, a linkage between the New York State
      Cancer Registry (NYSCR) and its Medicare programs, and prospective cohort studies
      Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) and the
      National Comprehensive Cancer Network. Data sets were analyzed in parallel using
      covariate adjusted and propensity score (PS) matched proportional hazards models
      to evaluate the effect of treatment on survival. PS trimming was used to mitigate
      the effects of selection bias. RESULTS: Use of adjuvant therapy declined with age
      and comorbidity. Chemotherapy receipt was associated with a survival benefit of
      comparable magnitude to clinical trials results (SEER-Medicare PS-matched
      mortality, hazard ratio [HR], 0.60; 95% CI, 0.53 to 0.68). The incremental
      benefit of oxaliplatin over non-oxaliplatin-containing regimens was also of
      similar magnitude to clinical trial results (SEER-Medicare, HR, 0.84; 95% CI,
      0.69 to 1.04; NYSCR-Medicare, HR, 0.82, 95% CI, 0.51 to 1.33) in two of three
      examined data sources. However, statistical significance was inconsistent. The
      beneficial effect of chemotherapy and oxaliplatin did not seem solely
      attributable to confounding. CONCLUSION: The noninvestigational experience
      suggests patients with stage III CC >= 75 years of age may anticipate a survival
      benefit from adjuvant chemotherapy. Oxaliplatin offers no more than a small
      incremental benefit. Use of adjuvant chemotherapy after the age of 75 years
      merits consideration in discussions that weigh individual risks and preferences.

PMID- 22665538
TI  - The inadequacy of 20 dollars.

PMID- 22665537
TI  - Immunohistochemical double-hit score is a strong predictor of outcome in patients
      with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide,
      doxorubicin, vincristine, and prednisone.
AB  - PURPOSE: Approximately 5% of diffuse large B-cell lymphomas (DLBCLs) are double
      hit lymphomas (DHLs) with translocations of both MYC and BCL2. DHLs are
      characterized by poor outcome. We tested whether DLBCLs with high expression of
      MYC protein and BCL2 protein share the clinical features and poor prognosis of
      DHLs. PATIENTS AND METHODS: Paraffin-embedded lymphoma samples from 193 patients
      with de novo DLBCL who were uniformly treated with rituximab, cyclophosphamide,
      doxorubicin, vincristine, and prednisone (R-CHOP) were studied using
      immunohistochemistry for MYC, BCL2, CD10, BCL6, and MUM1/interferon regulatory
      factor 4, and fluorescent in situ hybridization (FISH) for MYC and BCL2. RESULTS:
      FISH analysis identified DHL in 6% of patients, who showed the expected poor
      overall survival (OS; P = .002). On the basis of immunohistochemical MYC and BCL2
      expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The
      DHS-2 group, defined by high expression of both MYC and BCL2 protein, comprised
      29% of the patients. DHS 2 was significantly associated with lower complete
      response rate (P = .004), shorter OS (P < .001), and shorter progression-free
      survival (PFS; P < .001). The highly significant correlation with OS and PFS was
      maintained in multivariate models that controlled for the International
      Prognostic Index and the cell-of-origin subtype (OS, P < .001; PFS, P < .001).
      DHS was validated in an independent cohort of 116 patients who were treated with
      R-CHOP. CONCLUSION: The immunohistochemical DHS defined a large subset of DLBCLs
      with double-hit biology and was strongly associated with poor outcome in patients
      treated with R-CHOP.

PMID- 22665539
TI  - Outcome of children with metastatic medulloblastoma treated with carboplatin
      during craniospinal radiotherapy: a Children's Oncology Group Phase I/II study.
AB  - PURPOSE: We evaluated the feasibility of administering carboplatin as a
      radiosensitizer during craniospinal radiation therapy (CSRT) to patients with
      high-risk medulloblastomas (MBs) and supratentorial primitive neuroectodermal
      tumors, and we report the outcome in the subset with metastatic (M+) MB. PATIENTS
      AND METHODS: After surgery, patients received 36 Gy CSRT with boosts to sites of
      disease. During radiation, patients received 15 to 30 doses of carboplatin (30-45
      mg/m(2)/dose), along with vincristine (VCR) once per week for 6 weeks. Patients
      on regimen A received 6 months of maintenance chemotherapy (MC) with
      cyclophosphamide and VCR. Once the recommended phase II dose (RP2D) of
      carboplatin was determined, cisplatin was added to the MC (regimen B). RESULTS:
      In all, 161 eligible patients (median age, 8.7 years; range, 3.1 to 21.6 years)
      were enrolled. Myelosuppression was dose limiting and 35 mg/m(2)/dose * 30 was
      determined to be the RP2D of carboplatin. Twenty-nine (36%) of 81 patients with
      M+ MB had diffuse anaplasia. Four patients were taken off study within 11 months
      of completing radiotherapy for presumed metastatic progression and are long-term
      survivors following palliative chemotherapy. Excluding these four patients, 5
      year overall survival +/- SE and progression-free survival +/- SE for M+ patients
      treated at the RP2D on regimen A was 82% +/- 9% and 71% +/- 11% versus 68% +/-
      10% and 59% +/- 10% on regimen B (P = .36). There was no difference in survival
      by M stage. Anaplasia was a negative predictor of outcome. CONCLUSION: The use of
      carboplatin as a radiosensitizer is a promising strategy for patients with M+ MB.
      Early progression should be confirmed by biopsy.

PMID- 22665540
TI  - Phase II trial of trastuzumab in combination with cytotoxic chemotherapy for
      treatment of metastatic osteosarcoma with human epidermal growth factor receptor
      2 overexpression: a report from the children's oncology group.
AB  - PURPOSE: Despite efforts to intensify chemotherapy, survival for patients with
      metastatic osteosarcoma remains poor. Overexpression of human epidermal growth
      factor receptor 2 (HER2) in osteosarcoma has been shown to predict poor
      therapeutic response and decreased survival. This study tests the safety and
      feasibility of delivering biologically targeted therapy by combining trastuzumab
      with standard chemotherapy in patients with metastatic osteosarcoma and HER2
      overexpression. PATIENTS AND METHODS: Among 96 evaluable patients with newly
      diagnosed metastatic osteosarcoma, 41 had tumors that were HER2-positive by
      immunohistochemistry. All patients received chemotherapy with cisplatin,
      doxorubicin, methotrexate, ifosfamide, and etoposide. Dexrazoxane was
      administered with doxorubicin to minimize the risk of cardiotoxicity from
      treatment with trastuzumab and anthracycline. Only patients with HER2
      overexpression received concurrent therapy with trastuzumab given for 34
      consecutive weeks. RESULTS: The 30-month event-free and overall survival rates
      for patients with HER2 overexpression treated with chemotherapy and trastuzumab
      were 32% and 59%, respectively. For patients without HER2 overexpression, treated
      with chemotherapy alone, the 30-month event-free and overall survival rates were
      32% and 50%, respectively. There was no clinically significant short-term
      cardiotoxicity in patients treated with trastuzumab and doxorubicin. CONCLUSION:
      Despite intensive chemotherapy plus trastuzumab for patients with HER2-positive
      disease, the outcome for all patients was poor, with no significant difference
      between the HER2-positive and HER2-negative groups. Although our findings suggest
      that trastuzumab can be safely delivered in combination with anthracycline-based
      chemotherapy and dexrazoxane, its therapeutic benefit remains uncertain.
      Definitive assessment of trastuzumab's potential role in treating osteosarcoma
      would require a randomized study of patients with HER2-positive disease.

PMID- 22665541
TI  - Multicenter, double-blind, placebo-controlled, randomized phase II trial of
      gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant
      mesothelioma.
AB  - PURPOSE: Gemcitabine plus cisplatin is active in malignant mesothelioma (MM),
      although single-arm phase II trials have reported variable outcomes. Vascular
      endothelial growth factor (VEGF) inhibitors have activity against MM in
      preclinical models. We added the anti-VEGF antibody bevacizumab to
      gemcitabine/cisplatin in a multicenter, double-blind, placebo-controlled
      randomized phase II trial in patients with previously untreated, unresectable MM.
      PATIENTS AND METHODS: Eligible patients had an Eastern Cooperative Oncology Group
      (ECOG) performance status of 0 to 1 and no thrombosis, bleeding, or major blood
      vessel invasion. The primary end point was progression-free survival (PFS).
      Patients were stratified by ECOG performance status (0 v 1) and histologic
      subtype (epithelial v other). Patients received gemcitabine 1,250 mg/m(2) on days
      1 and 8 every 21 days, cisplatin 75 mg/m(2) every 21 days, and bevacizumab 15
      mg/kg or placebo every 21 days for six cycles, and then bevacizumab or placebo
      every 21 days until progression. RESULTS: One hundred fifteen patients were
      enrolled at 11 sites; 108 patients were evaluable. Median PFS time was 6.9 months
      for the bevacizumab arm and 6.0 months for the placebo arm (P = .88). Median
      overall survival (OS) times were 15.6 and 14.7 months in the bevacizumab and
      placebo arms, respectively (P = .91). Partial response rates were similar (24.5%
      for bevacizumab v 21.8% for placebo; P = .74). A higher pretreatment plasma VEGF
      concentration (n = 56) was associated with shorter PFS (P = .02) and OS (P =
      .0066), independent of treatment arm. There were no statistically significant
      differences in toxicity of grade 3 or greater. CONCLUSION: The addition of
      bevacizumab to gemcitabine/cisplatin in this trial did not significantly improve
      PFS or OS in patients with advanced MM.

PMID- 22665542
TI  - Alterations in brain activation during working memory processing associated with
      breast cancer and treatment: a prospective functional magnetic resonance imaging
      study.
AB  - PURPOSE: To prospectively examine alterations in working memory (WM) -associated
      brain activation related to breast cancer and treatment by using functional
      magnetic resonance imaging. PATIENTS AND METHODS: Patients treated with
      chemotherapy (CTx+; n = 16) or without chemotherapy (CTx-; n = 12) and healthy
      controls (n = 15) were scanned during an n-back task at baseline (after surgery
      but before radiation, chemotherapy, and/or antiestrogen treatment), 1 month after
      completion of chemotherapy (M1), and 1 year later (Y1), or at yoked intervals for
      CTx- and controls. SPM5 was used for all image analyses, which included cross
      sectional between-group and group-by-time interaction and longitudinal within
      group analyses, all using a statistical threshold of 0.001. RESULTS: At baseline,
      patients with cancer showed increased bifrontal and decreased left parietal
      activation compared with controls. At M1, both cancer groups showed decreased
      frontal hyperactivation compared with controls, with increased hyperactivation at
      Y1. These cross-sectional findings were confirmed by group-by-time interaction
      analyses, which showed frontal activation decreases from baseline to M1 in
      patients compared with controls. Within-group analyses showed different patterns
      of longitudinal activation change by treatment group (CTx+ or CTx-), with
      prominent alterations in the frontal lobes bilaterally. CONCLUSION: Significant
      frontal lobe hyperactivation to support WM was found in patients with breast
      cancer. Superimposed on this background, patients showed decreased frontal
      activation at M1, with partial return to the previously abnormal baseline at Y1.
      These functional changes correspond to frontal lobe regions where we previously
      reported structural changes in this cohort and provide prospective, longitudinal
      data that further elucidate mechanisms underlying cognitive effects related to
      breast cancer and its treatment.

PMID- 22665543
TI  - Comparative genomic analysis of primary versus metastatic colorectal carcinomas.
AB  - PURPOSE: To compare the mutational and copy number profiles of primary and
      metastatic colorectal carcinomas (CRCs) using both unpaired and paired samples
      derived from primary and metastatic disease sites. PATIENTS AND METHODS: We
      performed a multiplatform genomic analysis of 736 fresh frozen CRC tumors from
      613 patients. The cohort included 84 patients in whom tumor tissue from both
      primary and metastatic sites was available and 31 patients with pairs of
      metastases. Tumors were analyzed for mutations in the KRAS, NRAS, BRAF, PIK3CA,
      and TP53 genes, with discordant results between paired samples further
      investigated by analyzing formalin-fixed, paraffin-embedded tissue and/or by 454
      sequencing. Copy number aberrations in primary tumors and matched metastases were
      analyzed by comparative genomic hybridization (CGH). RESULTS: TP53 mutations were
      more frequent in metastatic versus primary tumors (53.1% v 30.3%, respectively; P
      < .001), whereas BRAF mutations were significantly less frequent (1.9% v 7.7%,
      respectively; P = .01). The mutational status of the matched pairs was highly
      concordant (> 90% concordance for all five genes). Clonality analysis of array
      CGH data suggested that multiple CRC primary tumors or treatment-associated
      effects were likely etiologies for mutational and/or copy number profile
      differences between primary tumors and metastases. CONCLUSION: For determining
      RAS, BRAF, and PIK3CA mutational status, genotyping of the primary CRC is
      sufficient for most patients. Biopsy of a metastatic site should be considered in
      patients with a history of multiple primary carcinomas and in the case of TP53
      for patients who have undergone interval treatment with radiation or cytotoxic
      chemotherapies.

PMID- 22665544
TI  - Systemic retinoid therapy for chemoprevention of nonmelanoma skin cancer in a
      patient treated with vemurafenib.

PMID- 22665545
TI  - Adjuvant chemotherapy in older patients with stage III colon cancer: an underused
      lifesaving treatment.

PMID- 22665546
TI  - Secondary colorectal carcinoma after childhood cancer.
AB  - PURPOSE: Colorectal carcinoma (CRC) has been described as a subsequent malignant
      neoplasm (SMN), although little is known about associated risk factors. We aimed
      to quantify the long-term risk of secondary CRC and identify treatment-related
      risk factors. PATIENTS AND METHODS: In this nested case-control study, 19 cases
      of adenocarcinoma of the colon or rectum were identified from 13,048 oncology
      patients treated for childhood cancer at St Jude Children's Research Hospital.
      Group 1 controls (n = 148) were matched for age at primary malignancy and follow
      up interval. Group 2 controls (n = 72) were matched on primary diagnosis in
      addition to group 1 criteria. Exact conditional logistic regression was performed
      to calculate odds ratios (ORs) for chemotherapy and radiation exposure. RESULTS:
      Forty-year cumulative incidence of secondary CRC was 1.4%. Standardized incidence
      ratio was 10.9 (95% CI, 6.6 to 17.0) compared with that in the general US
      population. Secondary CRC was more likely in an irradiated segment of the colon
      (group 1 OR, 7.7; P = .001; group 2 OR, 15.4; P = .002). Risk increased by 70%
      with each 10-Gy increase in radiation dose. Increasing radiation volume increased
      risk (group 1 OR, 1.5; P < .001; group 2 OR, 1.8; P < .001). Alkylating agent
      exposure was associated with an 8.8-fold increased risk of secondary CRC (P =
      .03). CONCLUSION: In matched analyses, radiation and alkylator exposure are
      associated with secondary CRC. This risk is proportional to dose and volume of
      radiation. Surveillance should be initiated at a young age among survivors
      receiving high-risk exposures.

PMID- 22665547
TI  - Playing bad cards properly: challenges to improving cure rates in
      rhabdomyosarcoma.

PMID- 22665548
TI  - Lepromatous phlebitis of the left external jugular vein.

PMID- 22665549
TI  - Pseudo-ischaemic ECG in a patient with amyotrophic lateral sclerosis surviving
      for a decade.
AB  - A 58-year-old female with no history of heart disease was admitted to our
      hospital for abnormal ECG mimicking myocardial ischaemia. The ECG revealed
      persistent T-wave inversion in almost all leads, especially in precordial leads
      V2-V6. The patient had no complaints of chest pain, chest distress, short of
      breath or other atypical myocardial ischaemia symptoms. She had a history of
      amyotrophic lateral sclerosis (ALS) with a disease course more than 20 years.
      Examinations help rule out other diseases causing persistent T-wave inversion.
      Importantly, cardiac catheterisation showed nearly normal coronary arteries that
      could rule out myocardial ischaemia. Accordingly, the authors presumed that the
      pseudo-ischaemic ECG was associated with ALS in this patient. The findings of the
      present case provide new evidence that autonomic nervous system may involve in
      the pathophysiological progress of ALS.

PMID- 22665550
TI  - A fatal case of pulmonary nocardiosis.
AB  - Pulmonary nocardiosis is a serious, most often considered an opportunistic
      infection affecting the respiratory tract. Even though it is more common in
      immunocompromised hosts, it is not infrequently seen in immunocompetent patients
      as well. The aerosol route is the main portal of entry in to the body. Molecular
      techniques have revolutionised the identification of Nocardia species. However
      such tests are limited to referral laboratories. The radiographic appearances of
      Nocardia infection vary from a small nodule to bilateral infiltrates with
      cavitation. Traditionally sulphonamides have been considered the treatment of
      choice. However, resistance to sulphonamides is increasingly recognised.
      Carbapenems and linezolid have been found to be uniformly active against all the
      pathogenic species of Nocardia that affect human beings. The authors report a
      case of pulmonary nocardiosis in an immunocompetent patient, in whom the
      infection relentlessly progressed to florid sepsis despite prompt institution of
      right antibiotics. Florid sepsis relating to pulmonary nocardiosis is rare.

PMID- 22665551
TI  - Possible association between statin use and bowel dysmotility.
AB  - 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are a class
      of drug that has been proven to be effective in lowering serum lipid levels.
      Although generally well-tolerated side effects from this class of drug have been
      noted to include liver dysfunction, renal failure and myopathy. Statins are also
      known to effect nitric oxide levels through upregulation of nitric oxide
      synthase. There is some evidence to imply that nitric oxide acts on inhibitory
      nerves in the colon to produce impaired motility. The authors present a case of
      recurrent colonic dilatation and volvulus which was initially treated with a
      sigmoid colectomy. Unfortunately symptoms persisted and a trial of the omission
      of statins was undertaken resulting in symptomatic relief. Following admission
      into hospital, statins were inadvertently restarted which caused the symptoms to
      reoccur. The statin was discontinued and upon review several months later the
      patient reported symptomatic benefit.

PMID- 22665552
TI  - Salmonella kingabwa meningitis in a neonate.
AB  - A 23-day-old male baby was admitted with 1 day history of high temperature,
      irritability and poor feeding. His general examination was unremarkable.
      Salmonella species grew from CSF culture and subsequent identification revealed
      Salmonella kingabwa, a serotype which rarely causes human illness. The child
      lived with his parents and regularly visited his grandmother for 4 h every day.
      Grandmother kept five snakes and five water dragons as pets. They lived in tanks
      and crawled freely around the house. For decades the reptiles have been known to
      carry Salmonella, which can be transmitted directly or indirectly to humans
      through ingestion of the bacteria, which causes subsequent infection. Reptile
      exposure is a rare but significant risk factor for Salmonella illness in England
      and contact with reptiles should be avoided by children less than 5 years old,
      pregnant ladies, older and those with impaired immunity.

PMID- 22665554
TI  - Abdominal compartment syndrome due to subcutaneous emphysema.

PMID- 22665553
TI  - Triple negative mixed metaplastic breast carcinoma with squamous and spindle
      cells in an 84-year-old woman: a rare entity with unclear management strategy and
      poor prognosis.
AB  - Metaplastic carcinoma of the breast, a rare neoplasm, usually presents at an
      advanced stage, metastasises to distant sites more frequently, has higher Ki-67
      expression and is more often triple negative compared with other invasive breast
      cancers. Here, the authors discuss a case of an 84-year-old woman with triple
      negative mixed metaplastic breast carcinoma treated with radical modified
      mastectomy, axillary lymph node dissection and radiation therapy. Because of the
      rarity of the disease, the pathogenesis and the management remain controversial,
      thus contributing to overall poor prognosis.

PMID- 22665555
TI  - A rare ophthalmic presentation of pituitary metastases.
AB  - Metastasis to the pituitary gland is very uncommon and a first presentation of
      any systemic tumour through pituitary metastasis is rare. The authors report an
      82-year-old Caucasian woman, well-controlled hypertensive and moderate smoker who
      presented with worsening diplopia. On ocular motility examination she had partial
      right third nerve paralysis along with reduced vision in the right eye and
      headache. MRI brain showed a large growth in the pituitary gland consisting with
      radiological features of pituitary macroadenoma. The initial chest x-ray showed a
      non-specific shadow that raised some suspicions and a CT scan of her thorax
      confirmed a right central bronchial carcinoma. The authors suggest that pituitary
      gland metastases be considered as part of the differential diagnosis for any
      patient presenting with a pituitary lesion, as pituitary disease could be the
      first manifestation of an underlying malignancy.

PMID- 22665556
TI  - A patient presenting with generalised lympadenopathy--sarcoidosis, lymphoma or
      tuberculosis?
AB  - Sarcoidosis, lymphoma and tuberculosis can often present with similar clinical
      features - for example, lymphadenopathy, fever, malaise, weight loss, respiratory
      symptoms, hypercalcaemia - making the establishment of the diagnosis difficult.
      The authors present a case of a 62-year-old woman with an established diagnosis
      of sarcoidosis affecting the lymph nodes, who subsequently developed high-grade T
      cell non-Hodgkin's lymphoma; the patient was also treated for active tuberculosis
      at the same time. This case highlights that these conditions can co-exist and
      that the occurrence of new and rapidly progressive symptoms in patients with an
      established diagnosis should alert clinicians to vigilantly search for another
      possible diagnosis.

PMID- 22665557
TI  - Odontoid pannus formation in a patient with ankylosing spondylitis causing
      atlanto-axial instability.
AB  - Ankylosing spondylitis is one of the commonest inflammatory diseases of the axial
      skeleton and can be complicated by atlanto-axial instability. This serious and
      likely underestimated complication can be easily overlooked. However, there are
      clear features which can help alert suspicion to initiate the appropriate
      investigations with imaging that is very effective at diagnosing and assessing
      this complication. The authors report an unusual case where odontoid pannus
      formation, akin to that seen in rheumatoid arthritis, was the underlying cause.

PMID- 22665558
TI  - Protracted neuroborreliosis--an unusual cause of encephalomyelitis.
AB  - A 58-year-old lady with waxing and waning of non-specific symptoms including
      fatigue, dizziness, hearing loss and unsteady gait for 15 months, became acutely
      confused 12 h prior to presentation. On admission to a district hospital she was
      feverish and unresponsive. Her travel history consisted of visits to Argentina,
      Chile and the Outer Hebrides. CT of the brain was normal. Lumbar puncture
      demonstrated a lymphocytic pleocytosis of 500 cells, protein of 1 g/l, a low
      glucose ratio with negative cytology and viral PCR (including herpes simplex 1
      and 2). MRI revealed multiple abnormal areas of high signal on T2 fluid
      attenuated inversion recovery sequencing within the cerebellum, temporal lobes
      and periventricular areas. Western blotting of serum and cerebrospinal fluid for
      Borrelia burgdoferi were both positive. She was treated with cefuroxime and
      aciclovir and within 24 h she was alert and responsive. She received 4 weeks of
      cefuroxime in total and made a good recovery.

PMID- 22665559
TI  - Spironolactone, a possible selective androgen receptor modulator, should be used
      with caution in patients with metastatic carcinoma of the prostate.
AB  - The authors report the case of an 80-year-old man who had heavily pretreated
      castration refractory carcinoma of the prostate and heart failure. Following the
      introduction of spironolactone to manage his heart failure, the patient
      experienced clinical and biochemical progression of his prostate cancer. Within 2
      weeks of withdrawing spironolactone the patient's prostate-specific antigen
      returned its previous level. This is the first reported case of clinical and
      biochemical progression of prostate cancer following the introduction of
      spironolactone. The authors propose that spironolactone is a selective androgen
      receptor modulator. Spironolactone should be used in caution with men with
      prostate cancer, and should not be used to treat oedema, hypokalaemia and
      hypertension associated with the newly licensed hormonal therapy abiraterone
      acetate.

PMID- 22665560
TI  - Tubercular dactylitis with discharging sinus in an adult patient.
AB  - Tubercular dactylitis, a term used for tuberculosis of short and tubular bones of
      hands and feet, rarely shows involvement of the foot. It is more commonly found
      in children as compared with adults. A 27-year-old male, came with history of
      discharging sinus over dorsum of great toe of right foot. Clinical assessment led
      to the suspicion of tuberculosis which was later confirmed by biopsy. This case
      highlights the importance relying on clinical impression and considering
      tuberculosis as an aetiology even at unusual sites of involvement.

PMID- 22665561
TI  - Acute pancreatitis with pancreatic abscess secondary to sealed jejunal
      diverticular perforation.
AB  - Although most cases of acute pancreatitis are attributed to gallstones or
      alcohol, many remain idiopathic. The authors describe a case of acute
      pancreatitis in a 75-year-old gentleman who presented with acute epigastric pain,
      fevers and shortness of breath. Serum amylase was 2164. CT showed free mesenteric
      air, and a partly cystic/partly gas-containing mass in the uncinate lobe of the
      pancreas. Gastrograffin meal revealed duodenal and jejunal diverticular disease,
      but no contrast leak. Further CT analysis pinpointed fine tracts of air leading
      from a jejunal diverticulum up toward the pancreas, suggesting causation by a
      sealed jejunal diverticular perforation. He responded well to intravenous
      antibiotics and conservative management. Although small bowel diverticular
      disease is linked to chronic pancreatitis, evidence for association with acute
      pancreatitis is scarce. The authors believe this is the first reported case of
      jejunal diverticular disease causing acute pancreatitis, and it highlights micro
      perforation as a potential disease mechanism.

PMID- 22665562
TI  - Do not miss rifampicin-induced thrombocytopenic purpura.
AB  - Drug-induced immune thrombocytopenia (DITP) can be triggered by a wide range of
      medications. Although many cases of DITP are mild, some are characterised by life
      threatening bleeding symptoms. In the treatment of tuberculosis there are special
      therapeutic problems related to adverse effects of drugs, compliance to treatment
      and microbial resistance. Thrombocytopenia is an uncommon but potentially fatal
      adverse effect of certain antituberculous drugs when the incriminating drug is
      taken by a susceptible individual. Here the authors report a case of rifampicin
      induced thrombocytopenia, which although rare, needs attention.

PMID- 22665563
TI  - Extra cranial invasive meningioma of fronto-temporo-parietal region of the skull
      vault.
AB  - Meningioma is the benign, unencapsulated neoplasm arising from meningo-epithelial
      arachnoid cells of cerebellopontine angle-internal auditory canal dura but
      extracranial meningiomas are very rare. In making the diagnosis of invasive
      meningioma, both changes of benign meningioma and invasive growth should be
      present. A case of the neglected invasive meningioma is described here which
      invaded approximately half of the fronto-temporo-parietal skull vault. The
      diagnosis was established and confirmed by the histopathology and
      immunohistochemistry, the cells were positive for epithelial membrane antigen,
      vimetin and progesterone receptors. The patient underwent surgical resection.

PMID- 22665564
TI  - Cavernous transformation of portal vein a missed cause of extrahepatic portal
      hypertension.
AB  - The portal vein thrombosis is an important and well-known cause of portal
      hypertension in young patients. Cavernous transformation of portal vein may be a
      sequel of portal vein thrombosis. Here the author reports a case of a 14-year-old
      boy presented with haemetemesis and melena, which was due to rupture of
      oesophageal varices as a result of portal hypertension. On further investigation,
      cavernous transformation of portal vein was identified on CT portovenogram and
      normal liver structure was evident on histology.

PMID- 22665565
TI  - A salty cause of severe hypertension.
AB  - A 51-year-old lady was referred to our clinic because of severe hypertension;
      blood pressure 214/119 mm Hg despite treatment with an angiotensin receptor
      antagonist and a calcium channel blocker. Her initial laboratory results showed
      hypokalaemic alkalosis with normal urea and creatinine levels. Her 24-h urinary
      sodium excretion was markedly elevated at 244 mmol (equivalent to a daily intake
      of approximately 16 g of salt). Hyperaldosteronism was suspected but her plasma
      aldosterone level was subsequently found to be normal. On further questioning,
      the patient admitted to eating considerable amounts of salted liquorice and a
      diagnosis of acquired apparent mineralocorticoid excess was made. Liquorice has a
      well-known mineralocorticoid activity as it inhibits the action of 11beta
      hydroxysteroid dehydrogenase 2 and can induce mineralocorticoid hypertension.
      After stopping eating the salted liquorice, the patient's blood pressure quickly
      normalised and all her antihypertensive medications were stopped.

PMID- 22665566
TI  - Primary pyomyositis: an unusual presentation in an older patient with no
      recognised risk factors.
AB  - Primary pyomyositis is a subacute deep bacterial infection of skeletal muscle. It
      is typically seen in tropical countries with Staphylococcus aureus being the
      commonest pathogen. Immunocompromised states and trauma are associated with cases
      in temperate climates where there is an increasing incidence, typically in
      children and young adults. However, the authors present a case of primary
      pyomyositis in a previously healthy 80-year-old female. The authors highlight the
      potential difficulties in early diagnosis of this rare condition in the UK
      indicating the need for early MRI imaging and the low sensitivity of blood
      cultures and serum creatine kinase measurements. Treatment, including early
      surgical drainage and appropriate antibiotic therapy, is discussed.

PMID- 22665567
TI  - Mesalazine-induced interstitial nephritis in a patient with ulcerative colitis.

PMID- 22665568
TI  - What could be the cause of late syncope after pacemaker implantation?
AB  - A 21-year-old man who had suffered an episode of complete heart block 2 months
      earlier and thus undergone pacemaker implantation presented with syncope.
      Echocardiography showed cardiac tamponade and raised the suspicion of lead
      penetration. The effusion was drained. Multi-sliced CT scan confirmed that the
      right aspect of the pacemaker wire was extracardiac, causing the cardiac
      tamponade.

PMID- 22665569
TI  - Coccidioidomycosis masquerading as malignancy.
AB  - Skeletal coccidioidomycosis is extremely rare and in the non-endemic areas,
      diagnosis is often delayed or missed resulting in extensive and unnecessary
      medical investigation for other diseases. The authors report a case of
      disseminated skeletal coccidioidomycosis in a previously healthy person living in
      a non-endemic area, who was initially thought to have a malignancy. Due to the
      presence of multiple expansile lytic bone lesions on x-rays and CT scan, an
      extensive investigation for malignancy was done. Diagnosis of coccidioidomycosis
      was made when H&E and Gomori's methenamine silver staining of a bone biopsy
      sample revealed multiple fungal spherules, which were confirmed to be
      Coccidioides immitis by culture and PCR. On questioning, the patient admitted to
      have spent 2 weeks in Arizona (an endemic area) few months ago. He was discharged
      home on long-term fluconazole. At 1 month clinical follow-up, a significant
      improvement in his lesions was noticed.

PMID- 22665570
TI  - Anticonvulsant-induced rickets and nephrocalcinosis.
AB  - Reported here is the case of a severely disabled young girl who developed Fanconi
      syndrome secondary to long-term valproic acid administration, ultimately leading
      to hypophosphatemic rickets. Although nephrocalcinosis is not a common feature in
      patients with proximal tubulopathy, the patient presented also with this
      condition, and the concomitant use of another anticonvulsant might have
      potentiated this condition. The purpose of this report is to increase awareness
      among healthcare providers of such rare but significant complications associated
      with anticonvulsants.

PMID- 22665571
TI  - Secondary omental torsion.
AB  - A middle-aged-woman presented with symptoms and signs of acute abdomen.
      Clinically a suspicion of acute appendicitis was raised, although the abdominal x
      ray and ultrasound were normal. She was managed conservatively, which she failed
      to respond. In the view of persisting pain, a contrast enhanced CT (CECT) was
      done. CECT showed a whirling mass of fatty and fibrous tissue adherent to the
      anterior abdominal wall suggestive of omental torsion and the diagnosis was
      confirmed on laparotomy and she underwent excision of the ischaemic omentum.
      Omental torsion though rare, should be included in the differential diagnosis of
      acute abdomen. High index of suspicion is required to diagnose this entity. CECT
      abdomen shows the classical finding of fatty mass with whirling pattern. It is
      seldom considered in the differential diagnosis preoperatively based on clinical
      findings and the diagnosis is only established during the surgical procedure.

PMID- 22665572
TI  - Management of a large retroperitoneal primitive neuroectodermal tumour: 'a
      multimodal approach'.
AB  - Retroperitoneal primitive neuroectodermal tumour (PNET) is a rare disease having
      poor prognosis. Treatment mainly consists of en block resection of the tumour to
      achieve RO resection, however multimodal approach has also been used with
      improved survival. The authors report a 40-year-old male with large
      retroperitoneal PNET adherent to aorta and compressing the inferior vena cava. He
      was subjected to P6 protocol chemotherapy (cyclophosphamide, adriamycin,
      vincristine, ifosfamide and etoposide) in view of borderline operability.
      Postchemotherapy contrast enhanced CT revealed significant reduction in size of
      the lesion. He underwent complete resection of the tumour followed by concurrent
      chemoradiation. He remains asymptomatic on follow-up over a period of 2 years.